PMID- 11567749
TI  - Change in the degree of adsorption of proteins by aluminum-containing adjuvants
      following exposure to interstitial fluid: freshly prepared and aged model
      vaccines.
AB  - The ability of interstitial fluid to change the degree of adsorption of ovalbumin
      to aluminum hydroxide adjuvant or lysozyme to aluminum phosphate adjuvant was
      studied. Ovalbumin and lysozyme were almost completely eluted after exposure at
      37 degrees C to sheep lymph fluid for 4h or 15 min, respectively. The ability of
      sheep lymph fluid to elute lysozyme from aluminum phosphate adjuvant did not
      change as the model vaccine aged. However, only 60% of the ovalbumin adsorbed to
      aluminum hydroxide adjuvant was eluted during exposure to sheep lymph fluid for
      24h after the model vaccine aged for 11 weeks at 4 degrees C.

PMID- 11567750
TI  - An E2 sub-unit marker vaccine does not prevent horizontal or vertical
      transmission of classical swine fever virus.
AB  - An experimental infection with classical swine fever (CSF) virus in E2 sub-unit
      marker vaccine vaccinated gilts was conducted in order to evaluate the effect of
      vaccination on virus transmission and course of the disease. Therefore, clinical
      signs as well as horizontal and vertical virus transmission were monitored in two
      inoculated, non-vaccinated and 10 vaccinated conventional gilts, housed in
      individual sow boxes. Within 10 days post-inoculation, all vaccinated gilts
      became infected. Depending on the definition of the infectious period, two
      different estimates of R0 were calculated (R0=14.8 and 3.3), both significantly
      larger than 1 (P<0.01). In three out of the eight vaccinated pregnant gilts
      vertical virus transmission occurred, resulting in infected offspring. Based on
      the results of this experiment, it can be concluded that double vaccination with
      an E2 sub-unit marker vaccine only protects pregnant gilts from the clinical
      course of the disease but does not prevent horizontal nor vertical spread of the
      CSF virus.

PMID- 11567751
TI  - Antibody responses to preS components after immunization of children with low
      doses of BioHepB.
AB  - BioHepB is a recombinant, hepatitis B vaccine derived from a mammalian cell line
      and containing HBs as well as preS1 and preS2 antigens, in their glycosylated and
      non-glycosylated forms. The vaccine was administered intramuscularly to 18
      children aged 5 months to 11 years at 0, 1 and 6 months. One hundred percent
      seroconversion and seroprotection rates were achieved after primary and secondary
      immunization with the 2.5 microg doses of BioHepB. Ten out of the 18 children
      (56%) responded with the appearance of anti-preS1 and/or anti-preS2 antibodies in
      circulation, when analyzed 1, 2, 6, 7 and 12 months after the initiation of
      vaccination. In comparison with the emergence of the anti-HBs response, early
      (month 2, after two injections) or late (month 7, after three injections) peak
      responses were noted for the kinetics of anti-preS1 and anti-preS2 production
      during the course of immunization, demonstrating that the anti-preS1 and anti
      preS2 responses are differently regulated, compared with the anti-HBs response.
      At month 6, just prior to the final injection, BioHepB caused significantly
      higher anti-HBs responses (GMT) in preS1-reactive children than in children
      without preS1 antibodies (P<0.005). Moreover, a significantly higher, anti-HBs
      response in GMT was also noted for anti-preS2-reactive children compared with
      anti-preS2-negative children (P<0.05). These findings demonstrated that
      recognition of the preS epitopes contained in the experimental preS1/preS2/S
      vaccine is accompanied by a more rapid onset and pronounced antibody response to
      the S-gene-derived protein in healthy children.

PMID- 11567752
TI  - Effect of the deletion of US2 and US3 from herpes simplex virus type 2 on immune
      responses in the murine vagina following intravaginal infection.
AB  - We investigated the effects of US2 and US3 deficiencies of herpes simplex virus
      type 2 (HSV-2) on host immunity in a murine model of genital herpes infection.
      Viral clearance from the vaginal mucosa was more rapid in mice infected with a
      US3-deficient mutant L1BR1 as compared with a wild-type 186 or YY2 (US2-deficient
      mutant) infection, although there was no significant difference among them in
      initial growth in the early stage of infection. Flow cytometric studies revealed
      that the number of vaginal mononuclear cells in L1BR1-infected mice was
      significantly greater than that in 186- or YY2-infected mice. Dendritic cells,
      macrophages and T cells were induced more rapidly and in greater numbers within
      the vaginas of L1BR1-infected mice. Moreover, the levels of IL-12 and IFN-gamma
      increased in L1BR1-infected mice over levels in 186-infected mice. These results
      indicate that a US3 deficiency alters the induction of the host immune response;
      therefore, the inactivation of US3 may be a promising strategy in the development
      of novel vaccines for genital herpes.

PMID- 11567753
TI  - Immunization with plasmid DNA encoding MHC class II binding peptide/CLIP-replaced
      invariant chain (Ii) induces specific helper T cells in vivo: the assessment of
      Ii p31 and p41 isoforms as vehicles for immunization.
AB  - A single helper T cell (Th) epitope-specific T cell subset was successfully
      induced in vivo by immunization with plasmid DNA encoding MHC class II binding
      peptide/class II-associated invariant chain peptide (CLIP)-replaced murine Ii
      molecules. Spleen cells from mice immunized by gene gun bombardment with plasmid
      DNA for Ii p31 and p41 molecules, whose CLIP regions were replaced with an I-A(d)
      restricted Th epitope, ovalbumin (OVA) 323-336, showed the specific proliferation
      and interferon-gamma (IFN-gamma) production. A20-2J B cell lines having these
      plasmids were capable of stimulating spleen cells from the immunized mice and
      naive DO10-transgenic mice bearing the epitope-specific T cell receptor (TCR)
      transgenes by examining the specific proliferative response and IFN-gamma
      production. Some mice immunized with the Ii p41-OVA323, but not with the Ii p31
      OVA323 plasmid, produced the peptide-specific antibodies, suggesting the
      functional difference between Ii isoforms.

PMID- 11567754
TI  - Improved vectors for expression library immunization--application to Mycoplasma
      hyopneumoniae infection in pigs.
AB  - Expression library immunization (ELI) has previously been used in a number of
      disease models in mice. Here, we describe the first example of the application of
      ELI to a large animal model with the immunization of pigs against enzootic
      pneumonia, a disease caused by Mycoplasma hyopneumoniae. The development of new
      plasmid vectors and library screening methods facilitated the application of ELI
      to this disease by allowing random libraries to be screened for clones expressing
      recombinant proteins. In this way the vast majority of clones in random libraries
      that are unproductive can be eliminated, meaning that libraries are more likely
      to give protection and are subsequently easier to further screen and analyze. By
      using this approach we have used one library screen and two animal trials to
      progress from an original library of 20,000 clones to a group of just 96 clones.

PMID- 11567755
TI  - Seroprevalence of varicella-zoster virus in the German population.
AB  - The present study was conducted to generate data on the epidemiology of varicella
      zoster virus (VZV) infections in Germany as a basis for health economic
      evaluations of varicella vaccination strategies. The survey was designed as a
      cross-sectional, age-stratified study of the VZV seroprevalence in the German
      population. The status of immunity of 4602 individuals a aged 0 to >70 years was
      investigated by means of an indirect enzyme immunoassay and the fluorescent
      antibody to membrane assay. After waning of maternal antibodies over the period
      of 6-9 months seropositivity rates remained low by the end of the 1st year of
      life. By the age of 4-5 years 62.5% (95% CI; 56.0-68.5) of the pre-school
      children had already been infected with VZV and at the age of 10-11 years 94.2%
      (95% CI; 91.0-96.0) of children were positive for anti-VZV antibodies. Among the
      age-group of >40 years old, only few individuals were susceptible for VZV. The
      median antibody levels to VZV did not significantly decline with increasing age.
      In comparison with figures of previous studies the age-specific seroprevalence
      data presented here do not provide evidence for an upward shift in the age
      distribution of varicella in Germany. Since the majority of VZV infections occurs
      during the early childhood, the best option to reduce the circulation of wild
      type VZV in the population would be the immunization of young children.

PMID- 11567756
TI  - Characterization of a human H9N2 influenza virus isolated in Hong Kong.
AB  - Two H9N2 viruses were isolated, for the first time, from humans in Hong Kong in
      1999. Isolation of influenza viruses with a novel subtype of the hemagglutinin
      (HA) drew attention of health care authorities worldwide from the view of
      pandemic preparedness. Sequence analysis of the HA genes reveals that HA of
      A/Hong Kong/1073/99 (H9N2) is most closely related to that of A/quail/HK/G1/97
      (H9N2) that contains the internal genes similar to those of Hong Kong/97 (H5N1)
      viruses. Phylogenetic and antigenic analyses demonstrated the diversity among H9
      HA. A/Hong Kong/1073/99 was shown to cause a respiratory infection in Syrian
      hamsters, suggesting that the virus can replicate efficiently in mammalian hosts.
      We developed a whole virion test vaccine with a formalin-inactivated egg-grown
      HK1073. Intraperitoneal administration of the vaccine twice to hamsters conferred
      a complete protection against challenge infection by the MDCK cell-grown
      homologous virus. Receptor specificity of HK1073 appeared different from that of
      other avian influenza viruses of H9 subtype which recognize preferentially alpha
      2,3 linked sialic acid. Hemagglutination of HK1073 with guinea pig erythrocytes
      was inhibited by both alpha-2,3 and alpha-2,6 linked sialic acid containing
      polymers. These data suggested that HK1073 had acquired a broader host range,
      including humans. Together with data so far available, the present study
      suggested that isolation of the H9 influenza viruses from humans requires
      precaution against the emergence of a novel human influenza.

PMID- 11567757
TI  - Nasal administration of cholera toxin (CT) suppresses clinical signs of
      experimental autoimmune encephalomyelitis (EAE).
AB  - Cholera toxin (CT), a major enterotoxin produced by Vibrio cholerae, elicits
      mucosal adjuvant activities by inducing antigen-specific CD4+ T cells secreting T
      helper type 2 (Th2) cytokines. Experimental autoimmune encephalomyelitis (EAE) is
      induced by Th1 cells specific for myelin-derived antigens. We induced EAE in
      C57BL/6 mice with myelin oligodendrocyte glycoprotein (MOG) 35-55 and CT was
      nasally administered as an immunomodulator on day 7 following MOG challenge.
      Clinical severity in the CT-treated mice was milder when compared to PBS-treated
      mice, while the levels of expression of interleukin (IL)-12 and interferon (IFN)
      gamma in the central nervous system (CNS) of CT-treated mice were lower than PBS
      treated mice. Thus, nasal administration of the mucosal immunomodulator CT
      ameliorated the severity of EAE, which was associated with the suppression of Th1
      cell responses.

PMID- 11567758
TI  - A crucial role of macrophages in the immune responses to oral DNA vaccination
      against hepatitis B virus in a murine model.
AB  - In the previous study, we had shown that live oral vaccination with Salmonella
      typhimurium delivering plasmid DNA-HBsAg (oral DNA vaccine) evoked a vigorous T
      cell response and a weak antibody response with predominant subclass IgG2a in
      mice, suggesting a significant involvement by professional antigen presenting
      cells (APC). In the present study, this possibility was further studied by
      infecting peritoneal macrophages (MPhi) with the oral DNA vaccine. Although, the
      infected cells could only express low level of the viral antigen, they
      nevertheless stimulated a vigorous lymphocyte proliferation of splenocytes from
      immune mice, induced these cells to elaborate interferon-gamma and stimulated
      development of HBV-specific cytotoxicity against target cells expressing the
      viral antigen. Infusion of the infected MPhi evoked a vigorous Th 1 and cytotoxic
      T lymphocyte (CTL) response and a weak IgG2a antibody response in mice, which was
      essentially the same as response to the oral DNA vaccine. In contrast,
      recombinant protein vaccine evoked a vigorous IgG1 antibody response and a weak T
      cell response. While, given intramuscularly, the same plasmid DNA vaccine as that
      contained in the oral DNA vaccine evoked a vigorous IgG1 antibody response and a
      moderate T cell response in these animals. It was concluded that professional APC
      may orchestrate the immune response to live oral DNA vaccine and it was of
      interest to note that different vaccine formulation and routes of administration
      evoke distinct immune response to HBV.

PMID- 11567759
TI  - Enhanced immune response to T-independent antigen by using CpG
      oligodeoxynucleotides encapsulated in liposomes.
AB  - Immunostimulatory CpG oligodeoxynucleotides (ODN) have been tested as
      immunoadjuvants for various vaccines including T-cell independent (TI) antigens.
      Findings from previous reports suggest that close physical association of CpG ODN
      to the antigen could enhance its adjuvant effect. As an alternative to chemical
      conjugation of CpG ODN to the antigen, the current study is aimed at determining
      the benefit of using liposomes as a carrier for CpG ODN to improve the immune
      response to biotinylated liposomes (Bx-liposomes), a model of a TI antigen.
      Liposomes with suboptimal concentration of hapten (1% biotin) were not
      immunogenic. However, when CpG ODN encapsulated in Bx-liposomes were used to
      immunize mice, a hapten-specific response was obtained as indicated by antibody
      mediated elimination of re-administered Bx-liposomes. CpG ODN co-administered
      with empty Bx-liposomes could not achieve the same effect, indicating the
      requirement for encapsulation of the adjuvant. Using both intravenous (i.v.) and
      subcutaneous (s.c.) immunization methods, it was found that IgM levels, but not
      IgG levels were elevated. Immunization in nude mice confirmed that the immune
      response obtained was TI. The use of non-CpG ODN and an ODN with alternatively
      flanked CpG motifs showed no adjuvant effect. Incorporation of
      poly(ethylene)glycol (PEG)-modified lipid in liposomes enhanced the immune
      response even further. In conclusion, our data shows that liposomes are a useful
      delivery vehicle for CpG ODN as an immune adjuvant for TI antigens.

PMID- 11567760
TI  - A single dose of an ISCOM influenza vaccine induces long-lasting protective
      immunity against homologous challenge infection but fails to protect Cynomolgus
      macaques against distant drift variants of influenza A (H3N2) viruses.
AB  - Since the production of influenza vaccines is complicated by the continuous
      variation of these viruses, it would be desirable to develop vaccines that induce
      cross-protective immunity against influenza virus strains that circulate in
      subsequent winter epidemics. We have recently demonstrated that antibodies
      induced after vaccination with an immune stimulating complex (ISCOM)-based
      vaccine exhibited a certain degree of cross-reactivity with other influenza virus
      strains. In the present study, ISCOM-based vaccines were evaluated
      retrospectively by testing the protective immunity induced by ISCOM prepared with
      the membrane glycoproteins of A/Philippines/2/82 against the more recent strain
      A/Netherlands/18/94 in monkeys with or without a history of prior infection with
      an A/Philippines/2/82-like virus. It was found that the monkeys immunized with
      the A/Philippines/2/82 ISCOM were not protected from challenge infection with
      A/Netherlands/18/94. On the other hand, vaccination of monkeys which experienced
      a prior infection with an influenza A/Philippines/2/82-like virus, with a single
      dose of ISCOM vaccine induced long-lasting protective immunity against challenge
      infection with the homologous virus A/Netherlands/18/94.

PMID- 11567761
TI  - Negligible adjuvant effect for antibody responses and frequent adverse events
      associated with IL-12 treatment in humans vaccinated with pneumococcal
      polysaccharide.
AB  - To assess whether co-administration of recombinant human IL-12 (rhIL-12) and 23
      valent pneumococcal polysaccharide vaccine (PPV) enhances the antibody response
      to this T cell-independent antigen, healthy immunocompetent volunteers (n=34, 55
      65 years old) were vaccinated intramusculary with PPV and concurrently-treated
      subcutaneously with either rhIL-12 (1 or 4 microg) or placebo. The increases of
      total anti-pneumococcal IgG antibodies were numerically higher among the rhIL-12
      recipients compared with placebo recipients, but the difference was not
      significant. The rhIL-12 recipients had a high incidence of local and systemic
      side effects. Given the lack of convincing evidence that rhIL-12 enhances the
      antibody response to PPV, the frequency and severity of the side effects was
      unacceptable.

PMID- 11567762
TI  - Induction of cytotoxic T lymphocyte responses against hepatitis delta virus
      antigens which protect against tumor formation in mice.
AB  - The cellular immune response is a crucial defense mechanism against hepatotropic
      viruses and in chronic viral hepatitis prevention. Moreover, hepatitis delta
      virus (HDV) immunogenicity may be an important component in the development of
      prophylactic and therapeutic vaccines. Therefore, we evaluated the immunogenicity
      of the small (HDAg) or large delta antigen (LHDAg) to be used as a DNA-based
      vaccine. We immunized different mouse haplotypes, determined cellular immune
      responses, and tested protection of animals against tumor formation using
      syngeneic tumor cells stably expressing the delta antigens. Both LHDAg and HDAg
      primed CD4+ and CD8+ T cell immunity against both forms of delta antigens. CD8+ T
      cell frequencies were about 1% and antigen-specific CD8+ T cells remained
      detectable directly ex vivo for at least 35 days post-injection. No anti-delta
      antibody responses could be detected despite multiple detection systems and
      varied immunization approaches. We observed protection against syngeneic tumor
      formation and growth in mice immunized with DNA plasmids encoding secreted or
      intracellular forms of HDAg and LHDAg but not with recombinant HDAg establishing
      the generation of significant cellular immunity in vivo. Both CD4+ and CD8+ T
      cells were required for antitumoral activity as determined by in vivo T cell
      depletion experiments. The results indicate that DNA-based immunization with
      genes encoding LHDAg and HDAg induces strong T cell responses and, therefore, is
      an attractive approach for the construction of therapeutic and prophylactic T
      cell vaccines against HDV.

PMID- 11567763
TI  - Protection against tick-transmitted Lyme disease in dogs vaccinated with a
      multiantigenic vaccine.
AB  - In an effort to develop a safe and effective vaccine for the prevention of Lyme
      borreliosis that addresses concerns raised over currently available vaccines,
      dogs were vaccinated twice with a multiantigenic preparation of Borrelia
      burgdorferi, strain N40, on days 0 and 20 of the experiment. About 70 and 154
      days after the first immunization, dogs were challenged by exposing them to field
      collected Ixodes scapularis ticks harboring B. burgdorferi. Vaccinated dogs were
      completely protected from infection by all criteria utilized to assess infection,
      developed high-titer anti-B. burgdorferi serum antibodies and growth inhibitory
      activity which persisted for over 200 days, and did not demonstrate any untoward
      consequence of vaccination. Serum absorption experiments revealed that
      borreliacidal and most likely protective antibodies in dogs receiving the
      multiantigenic preparation were not only elicited against the OspA antigen, but
      were also produced against additional yet to be determined targets on B.
      burgdorferi organisms. These data demonstrate that a multiantigenic vaccine is
      effective in preventing Lyme disease transmitted via the natural vector.

PMID- 11567764
TI  - Serum and salivary anti-capsular antibodies in infants and children vaccinated
      with octavalent pneumococcal conjugate vaccines, PncD and PncT.
AB  - We studied the immunogenicity of two octavalent pneumococcal (Pnc) conjugate
      vaccines; Pnc polysaccharides (PS) of serotypes 3, 4, 6B, 9V, 14, 18C, 19F, and
      23F were conjugated to diphtheria or tetanus toxoid (PncD and PncT,
      respectively). Fifty healthy Finnish infants were vaccinated at the ages of 2, 4,
      6, and 15 months with either PncD or PncT. Serum IgG antibodies to the vaccine
      serotypes were analysed by enzyme-linked immunosorbent assay (EIA). All eight PSs
      induced a significant antibody response both after the primary series and after
      the booster. Response to PncD was higher for PSs 3, 9V, 14 and 18C and to PncT
      for serotype 4. Salivary IgA and IgG anti-Pnc antibodies were measured for
      serotypes 4, 6B, 9V, 14, 18C, and 19F. Mucosal antibodies were found rarely after
      the primary series but in a greater proportion after the booster. In conclusion,
      both vaccines were immunogenic.

PMID- 11567765
TI  - Health economics of a hexavalent meningococcal outer-membrane vesicle vaccine in
      children: potential impact of introduction in the Dutch vaccination program.
AB  - The cost-effectiveness of universal vaccination of infants with a new hexavalent
      meningococcal B outer-membrane vesicle vaccine is projected for The Netherlands
      by applying decision analysis. The societal perspective is taken and direct and
      productivity costs (friction costs method) are considered. Future costs and
      effects are discounted at 4% (base year 1998). In this simulation model,
      vaccination would prevent 19 deaths and eight cases with severe long-term
      sequelae per year, rendering 526 additional quality adjusted life years (QALYs)
      per year. Yearly costs of acute phase of illness due to meningococcal infections
      in children are estimated at 1,426,634, while the future costs due to sequelae
      are estimated at 3,801,121 per year. Of all these costs, the vaccination program
      could prevent 3,334,052 per year. The program costs of meningococcal vaccination
      are estimated at 11,601,356, resulting in a cost-effectiveness ratio (CER) of
      15,721 per QALY. These results are sensitive to the vaccine dose price
      (conservatively estimated at 10), efficacy, and coverage of meningococcal sero
      subtypes.

PMID- 11567766
TI  - Targeting polymerised liposome vaccine carriers to intestinal M cells.
AB  - Due to their transcytotic capability, intestinal M cells may represent an
      efficient potential route for oral vaccine delivery. We previously demonstrated
      that the lectin Ulex europaeus agglutinin 1 (UEA1, specific for alpha-L-fucose
      residues) selectively binds to mouse Peyer's patch M cells and targets 0.5 microm
      polystyrene microparticles to these cells. Using a gut loop model we now
      demonstrate that covalently-membrane-bound UEA1 similarly targets polymerised
      liposomes (Orasomes, approximately 200 nm diameter), potential biocompatable oral
      vaccine delivery vehicles, to mouse M cells. Targeting was inhibited by alpha-L
      fucose while the co-entrapped adjuvant, monophosphoryl Lipid A (MPL), failed to
      exert any detrimental effect on UEA1-mediated M cell targeting. Lectin-mediated M
      cell targeting may thus permit the efficacy of mucosal vaccines to be enhanced if
      cellular relationship between particle binding and immune outcome can be
      established.

PMID- 11567767
TI  - Nasal immunization with subunit proteosome influenza vaccines induces serum HAI,
      mucosal IgA and protection against influenza challenge.
AB  - The immunogenicity of a mucosally delivered subunit influenza vaccine was
      assessed in mice. Split influenza virus vaccine (sFlu) was formulated with
      proteosomes (Pr-sFlu), administered intranasally, and the induced immunity was
      compared with the responses elicited by sFlu alone given either intramuscularly
      or intranasally. Intranasal (i.n.) immunization with Pr-sFlu induced specific
      serum IgG and hemagglutination inhibition (HAI) titers comparable to or better
      than those induced by intramuscular (i.m.) sFlu, and in contrast to sFlu alone,
      i.n. Pr-sFlu also induced high levels of influenza-specific IgA in lung and nasal
      washes. Mice receiving i.n. Pr-sFlu were completely protected against live virus
      challenge, as were mice immunized by injection with sFlu alone. The i.n. Pr-sFlu
      elicited cytokine responses polarized towards a type 1 phenotype whereas those
      elicited by sFlu alone were of a mixed type 1/type 2 phenotype. The data strongly
      suggest that i.n. proteosome-formulated influenza antigens are highly effective
      and are excellent candidates for a non-invasive human vaccine.

PMID- 11567768
TI  - Optimal age for vaccination against measles in the State of Sao Paulo, Brazil,
      taking into account the mother's serostatus.
AB  - In order to investigate if the changing levels of measles antibody in women
      resulting from extensive vaccination programs influence the susceptibility of
      children, we measured the seroprevalence of measles virus antibody of children in
      the first year of life and of their mothers. We compared maternal antibody decay
      of two groups of children: those whose mothers were 25 years old or more (mothers
      born in the pre-vaccination era), and less than 25 years old (mothers born in the
      vaccination era). Therefore, the 25-year-age cut-off was chosen to distinguish
      between vaccinated and non-vaccinated mothers. We also compared the
      immunogenicity of measles vaccine in children from 6 to 12 months of age, in
      these two groups and also according to their mother's serostatus. The optimal age
      of vaccination for a routine program was estimated by means of mathematical
      models. This study was carried out in a sample of 1216 mothers and their
      respective children. Our results indicate that the optimal age for vaccination of
      the whole sample was 15 months, 17 months for children born from older mothers,
      14 months for children born from younger mothers, 17 months for children born
      from seropositive mothers and 12 months for children born from seronegative
      mothers. Therefore, a change to an earlier age of routine vaccination is not
      justified by our results.

PMID- 11567769
TI  - Antibodies to BrkA augment killing of Bordetella pertussis.
AB  - BrkA is a Bvg-regulated Bordetella pertussis protein that mediates serum
      resistance and adherence. It shares sequence identity with another B. pertussis
      virulence factor called pertactin, and it is a member of the diverse group of
      proteins found in Gram-negative bacteria that are secreted by an autotransporter
      mechanism. Sera, either from individuals who have been vaccinated with acellular
      pertussis vaccines, or from individuals who have no re-collection of recent
      infection with B. pertussis fail to kill wild-type B. pertussis, but kill brkA
      mutant strains very well. We examined whether BrkA could be neutralised in serum
      fitting this profile. BrkA is synthesised as a 103kDa precursor that is processed
      into a surface-associated N-terminal 73kDa passenger domain, and an outer
      membrane embedded C-terminal 30kDa transporter moiety. Polyclonal antibodies were
      raised to a recombinant, re-folded histidine-tagged fusion protein representing
      the 73kDa passenger region. These anti-BrkA antibodies were shown to boost the
      existing bactericidal capacity of human serum against B. pertussis by
      neutralising BrkA.

PMID- 11567770
TI  - C3d enhancement of neutralizing antibodies to measles hemagglutinin.
AB  - Measles remains a major cause of worldwide infant mortality despite the use of
      current live attenuated vaccines. New approaches to measles virus (MV) vaccine
      development are critical to interrupt the spread of MV. In this study, we report
      the results using a DNA vaccine expressing a fusion of the measles hemagglutinin
      (H) protein and the complement component, C3d, to enhance the titers of
      neutralizing antibody. Plasmids were generated that expressed a secreted (s) form
      of H and the same form fused to three tandem copies of the murine homologue of
      C3d (sH-3C3d). Analysis of titers of the antibody raised in vaccinated mice
      indicated that immunizations with the DNA expressing sH-3C3d had higher titers of
      anti-H antibodies compared to serum from mice vaccinated with DNA expressing sH
      only. In addition, sH-3C3d elicited higher neutralizing antibody titers that
      inhibited MV induced plaque formation.

PMID- 11567771
TI  - In vitro processing and presentation of a lipidated cytotoxic T-cell epitope
      derived from measles virus fusion protein.
AB  - Lipopeptidic formulations have been described as efficient activators of
      cytotoxic T lymphocytes (CTL). To better understand the pathway via which
      lipopeptides reach the MHC class I molecules we studied the intracellular
      processing and presentation of a measles virus-derived CTL epitope, to which a
      palmitoyl moiety was added synthetically. The palmitoyl group was conjugated to
      the N-terminus either directly or via a spacer sequence. The use of single or
      double fluorescent-labeled lipopeptides allowed the visualization of
      intracellular processing of these antigens using confocal microscopy. Our data
      indicate that the spacer composition influences internalization of the conjugate
      into the cell, proteasomal degradation, translocation into the ER by the
      transporter associated with antigen processing (TAP), and the intracellular
      trafficking of lipopeptides.

PMID- 11567772
TI  - Synthetic peptide vaccine against Taenia solium pig cysticercosis: successful
      vaccination in a controlled field trial in rural Mexico.
AB  - Taenia solium cysticercosis seriously affects human health when localised in the
      central nervous system (CNS) and causes great economic loss in pig husbandry in
      rural areas of endemic countries. Increasing the resistance to the parasite in
      the obligatory host pig may help in curbing transmission. Three synthetic
      peptides based on protein sequences of the murine parasite Taenia crassiceps,
      which had previously been shown to induce protection in mice against homologous
      challenge, were tested as a vaccine against T. solium cysticercosis in pigs.
      Vaccinated and unvaccinated piglets (240 in all) were distributed in pairs among
      the peasants' households of two rural villages in Mexico in which 14% of the
      native pigs were cysticercotic. Ten to twelve months later, the effect of
      vaccination was evaluated at necropsy. Vaccination decreased the total number of
      T. solium cysticerci (98.7%) and reduced the prevalence (52.6%). The natural
      challenge conditions used in this field trial strengthen the likelihood of
      successful transmission control to both pig and human through a large-scale pig
      vaccination program. We believe this is a major contribution in anticysticercosis
      vaccine development as these rather simple yet protective peptides are
      potentially more cost-effective to produce and less variable in results than
      antigens that are more complex.

PMID- 11567773
TI  - Adjuvant effects of IL-1beta, IL-2, IL-8, IL-15, IFN-alpha, IFN-gamma TGF-beta4
      and lymphotactin on DNA vaccination against Eimeria acervulina.
AB  - Eight chicken cytokine genes (IL-1beta, IL-2, IL-8, IL-15, IFN-alpha, IFN-gamma,
      TGF-beta4, lymphotactin) were evaluated for their adjuvant effect on a suboptimal
      dose of an Eimeria DNA vaccine carrying the 3-1E parasite gene (pcDNA3-1E).
      Chickens were given two subcutaneous injections with 50 microg of the pcDNA3-1E
      vaccine plus a cytokine expression plasmid 2 weeks apart and challenged with
      Eimeria acervulina 1 week later. IFN-alpha (1 microg) or 10 microg of
      lymphotactin expressing plasmids, when given simultaneously with the pcDNA3-1E
      vaccine, significantly protected against body weight loss induced by E.
      acervulina. Parasite replication was significantly reduced in chickens given the
      pcDNA3-1E vaccine along with 10 microg of the IL-8, lymphotactin, IFN-gamma, IL
      15, TGF-beta4, or IL-1beta plasmids compared with chickens given the pcDNA3-1E
      vaccine alone. Flow cytometric analysis of duodenum intraepithelial lymphocytes
      showed chickens that received the pcDNA3-1E vaccine simultaneously with the IL-8
      or IL-15 genes had significantly increased CD3+ cells compared with vaccination
      using pcDNA3-1E alone or in combination with the other cytokine genes tested.
      These results indicate that the type and the dose of cytokine genes injected into
      chickens influence the quality of the local immune response to DNA vaccination
      against coccidiosis.

PMID- 11567774
TI  - Enhancement of the immune response in rabbits to a malaria DNA vaccine by
      immunization with a needle-free jet device.
AB  - We compared the needle free jet device device Biojector with syringe/needle as a
      method to administer a DNA vaccine encoding the Plasmodium falciparum
      circumsporozoite protein (PfCSP) in albino rabbits. A group of three rabbits was
      injected by the intramuscular (IM) route using a syringe/needle combination, a
      second group IM with the Biojector device and a third group both IM and
      intradermal (ID) using the Biojector. When animals were immunized with the
      Biojector IM or IM/ID as compared to the syringe/needle IM, we observed 10- and
      50-fold greater antibody titers, as measured by enzyme immunoassay (EIA) and
      indirect fluorescence antibody test (IFAT), respectively. We also observed that
      the Biojector conferred a greater ability to prime the immune system as compared
      with the needle. The subsequent boosting of all animals with a recombinant canary
      pox virus (ALVAC) expressing PfCSP induced significantly higher titers in both
      Biojector groups of rabbits as compared with the needle and naive animals. These
      results provided the foundation for a clinical trial using the same regime.

PMID- 11567776
TI  - Toxicity, metabolism, and impact of mycotoxins on humans and animals.
AB  - The worldwide contamination of foods and feeds with mycotoxins is a significant
      problem. Mycotoxins are secondary metabolites of molds that have adverse effects
      on humans, animals, and crops that result in illnesses and economic losses.
      Aflatoxins, ochratoxins, trichothecenes, zearelenone, fumonisins, tremorgenic
      toxins, and ergot alkaloids are the mycotoxins of greatest agro-economic
      importance. Some molds are capable of producing more than one mycotoxin and some
      mycotoxins are produced by more than one fungal species. Often more than one
      mycotoxin is found on a contaminated substrate. Factors influencing the presence
      of mycotoxins in foods or feeds include environmental conditions related to
      storage that can be controlled. Other extrinsic factors such as climate or
      intrinsic factors such as fungal strain specificity, strain variation, and
      instability of toxigenic properties are more difficult to control. Mycotoxins
      have various acute and chronic effects on humans and animals (especially
      monogastrics) depending on species and susceptibility of an animal within a
      species. Ruminants have, however, generally been more resistant to the adverse
      effects of mycotoxins. This is because the rumen microbiota is capable of
      degrading mycotoxins. The economic impact of mycotoxins include loss of human and
      animal life, increased health care and veterinary care costs, reduced livestock
      production, disposal of contaminated foods and feeds, and investment in research
      and applications to reduce severity of the mycotoxin problem. Although efforts
      have continued internationally to set guidelines to control mycotoxins, practical
      measures have not been adequately implemented.

PMID- 11567777
TI  - Cerebral activation and distribution of inducible hsp110 and hsp70 mRNAs
      following focal ischemia in rat.
AB  - A potential function for inducible heat shock protein 70 (hsp70i) expression in
      the pathophysiology of ischemic brain has been well documented. The recently
      cloned hsp70 superfamily member, hsp110, was shown to be highly expressed in the
      brain and suggested to have a similar functional property as members of the hsp70
      family. In this study, as an initial step to probe for its physiological
      significance in the ischemic brain, cerebral activation and distribution of
      hsp110 mRNA was comparatively evaluated with that of hsp70i mRNA by in situ
      hybridization. A rat focal cerebral ischemia model was employed to examine the
      distribution and localization of hsp110 and hsp70i mRNAs in both affected
      (ipsilateral) and unaffected (contralateral) hemispheres of the same animal. Our
      results demonstrated a significant accumulation of hsp110 as well as hsp70i mRNAs
      following ischemia; although the magnitude and kinetics of induction differ
      slightly, spatial expression profiles of hsp110 and hsp70i mRNAs were highly
      correlated in the affected region. In control brain, limited hybridization signal
      was observed with 3'-untranslated region (UTR) containing hsp110 probe,
      suggesting a possible existence of inducible hsp110 and a selective recognition
      of our 3'-UTR containing probe for the inducible hsp110 mRNA species. Subsequent
      2D western analysis with Hsp110 specific Ab was consistent with our view, which
      resolved constitutive and inducible immunostained spots in rat ischemic brain.
      Considering a regulatory similarity as well as previously documented structural
      and functional similarities between hsp110 and hsp70i, we propose that
      coordinated cerebral activation of hsp110 and hsp70i is likely to be of
      significant relevance in the context of pathophysiology of ischemic brain.
      Further study is required to characterize the genetic and biochemical nature of
      rat inducible hsp110 identified in the current study.

PMID- 11567778
TI  - Mechanisms in fluoride-induced interleukin-8 synthesis in human lung epithelial
      cells.
AB  - Sodium fluoride (NaF) has previously been reported to induce a strong IL-8
      response in human epithelial lung cells (A549) via mechanisms that seem to
      involve the activation of G proteins. In the present study the signal pathways
      downstream of the G proteins have been examined. NaF induced a weak, but
      sustained increase in PKC activity. In contrast, the PKC activator TPA induced a
      relatively strong, but transient effect and augmented the NaF-induced PKC
      activity. TPA induced a marked IL-8 response compared to NaF. PDB, another PKC
      activator, was less effective, but augmented the IL-8 response to NaF.
      Pretreatment with TPA for 20 h, or the PKC inhibitor GF109203X for 1 h, abolished
      the basal and NaF-induced PKC activities and partially prevented the NaF-induced
      IL-8 response. Inhibition of the MAP kinase p38 by SB202190 partially reduced the
      IL-8 response to NaF, whereas a reduction in ERK activity by PD98059 led to an
      increased response. The NaF-induced IL-8 response was weakly augmented by the PKA
      stimulator forskolin and the G(i) inhibitor pertussis toxin. The PKA inhibitor
      H89 seemed to reduce the NaF-induced IL-8 response, but the measured effect was
      not statistically significant. BAPTA-AM, KN93 and W7, that inhibit Ca(2+)-linked
      effects, did not affect the IL-8 response. Furthermore, the tyrosine kinase
      inhibitor genestein, the PI-3 kinase inhibitor wortmannin and phosphatase
      inhibition were without effects. In conclusion, the data suggest that NaF-induced
      increase of IL-8 in A549 cells involved PKC- and p38-linked pathways, whereas an
      ERK-dependent pathway counteracted the response. Tyrosine kinases, Ca(2+)-linked
      pathways, PI-3 kinase, PKA and phosphatase inhibition seem to play no or minor
      roles in the fluoride-induced IL-8 response.

PMID- 11567779
TI  - Effect of dietary zinc deficiency on hematological and biochemical parameters and
      concentrations of zinc, copper, and iron in growing rats.
AB  - Zinc has a wide spectrum of biological activities and its deficiency has been
      related to various dysfunctions and alterations of normal cell metabolism. The
      effects of adequate Zn level (38 mg/kg diet, control) and two low levels that
      create Zn deficiencies (19 mg/kg diet, 1/2 of control and 3.8 mg/kg diet, 1/10 of
      control) were investigated in growing male and female rats for 10 weeks. This
      allowed for evaluation of the effects these Zn levels may have on body weight
      gain, specific organ weights, blood parameters, and serum concentrations of Zn,
      Cu and Fe. Rats fed Zn-deficient diets gained less (P<0.05) than the control
      groups. There was increase (P<0.05) in liver and spleen weights, and a decrease
      (P<0.05) in testes weight. However, brain, kidney, heart, and lung weights were
      not affected (P<0.05). Hematological parameters that were decreased (P<0.05) by
      Zn deficiency included hemoglobin (Hb), total erythrocyte count (TEC) and packed
      cell volume (PCV) with the magnitude being dose-dependent. Serum concentrations
      of total protein, globulin, glucose, and high density lipoprotein (HDL) also
      decreased (P<0.05) in a dose-dependent manner. Zn deficiency increased (P<0.05)
      total leukocyte count (TLC) and concentrations of serum albumin, total lipids,
      cholesterol, triglycerides and low density lipoprotein (LDL) in a dose-dependent
      manner. Serum concentrations of urea and creatinine were, however, not affected
      (P<0.05) by zinc deficiency. Zn-deficient rats had lower serum concentrations of
      Zn, Cu and Fe. These results showed that Zn deficiency has negative effects on
      growth rate, specific organ weights, hematological parameters, and serum levels
      of Zn, Cu and Fe, especially in rats fed the lowest Zn level.

PMID- 11567780
TI  - Lumbar spinal cord explants from neonatal rat display age-related decrease of
      outgrowth in culture.
AB  - Lumbar spinal cord explants, harvested from neonatal rat pups aged between
      postnatal day 0 (P0) and P7, were cultured for a period of 48 h in the chemically
      defined medium R(12) [17] (Romijn, H.J., van-Huijen, F., Wolters, P.S., Neurosci
      Biobehav Rev, 8 (1984) 301-334), embedded in a collagen matrix. The outgrowth
      into the surrounding matrix was quantified. Age-matched cortical explants were
      used as controls. Despite adaptations of the culture protocol, outgrowth remained
      variable. Statistical analysis demonstrated a clear relation between the age of
      the explant (at the time of explantation) and the number of neurites in the
      corona surrounding the explant. The number of outgrowing neurites decreased
      sharply with age. The average number of neurites per explant obeyed to the
      expression log(N)= -0.652 A+17 (N: the number of neurites per explant; A: the age
      expressed in gestational days; A epsilon [G23-G30]; G23 signifying gestational
      day 23, or P0). The observed age-related decrease of outgrowth could not be
      explained by progressive myelination of the spinal cord white matter, nor by the
      absence of trophic support from muscle, but may be related to a progressive
      inability of the spinal neurites to interact with collagen.

PMID- 11567781
TI  - The effect of expertise in gymnastics on proprioceptive sensory integration in
      human subjects.
AB  - The ability of experts in motor skills requiring a fine postural control to keep
      a stable upright posture while facing the task of reinserting proprioceptive
      information was investigated. Seven expert gymnasts and seven experts in other
      non-gymnastics sports were asked to stand as immobile as possible in two
      conditions of vision and no-vision. Within a trial, ankle proprioceptive input
      was modified by means of tendon vibration of both antagonistic ankle muscles.
      Center of foot pressure (COP) displacements were recorded using a force platform.
      Contrasting with the non-gymnasts, the gymnasts were able to rapidly take
      advantage of the reinsertion of proprioceptive information to decrease their COP
      displacements. These results suggest that the efficiency of the integration
      process leading to the reweighting of sensory information can be significantly
      improved through a specific training.

PMID- 11567782
TI  - Oxidised adenosine 5'-triphosphate, a P2X(7) antagonist, is toxic to rat
      cerebellar granule neurones in vitro.
AB  - Adenosine 5'-triphosphate (ATP) acts as a neurotransmitter in the central nervous
      system. Extracellular ATP is also toxic to a number of cell types e.g. via its
      interaction with P2X membrane receptors, specifically the P2X(7) family member.
      These results have led to the hypothesis that elevated ATP levels may exacerbate
      damage during acute neurodegeneration [4]. The aim of this study was to examine
      the effects of ATP agonists and antagonists on cultured rat cerebellar granule
      neurones. Neither ATP, nor the P2X agonist benzoylbenzoyl-ATP (BzATP), were toxic
      when added to primary neurones. However, the P2X(7) antagonist, oxidised ATP
      (oATP) was highly neurotoxic. This toxicity was inhibited by co-incubation with
      BzATP. These results demonstrate that oATP is a potent neurotoxin.

PMID- 11567783
TI  - Positron emission tomography shows that impaired frontal lobe functioning in
      Parkinson's disease is related to dopaminergic hypofunction in the caudate
      nucleus.
AB  - We examined the relation between the dopaminergic function and the cognitive
      performance of patients with Parkinson's disease (PD). The subject sample
      consisted of ten patients in the early course of PD and with no previous
      antiparkinsonian medication. The dopaminergic function of the caudate nucleus and
      the putamen was studied with [(18)F]fluorodopa positron emission tomography, and
      the cognitive performance with a comprehensive battery of neuropsychological
      tests including tests sensitive to frontal lobe function. The decreased
      [(18)F]fluorodopa uptake in the right caudate nucleus was found to be related to
      slow processing time, measured as the difference between the incongruent and the
      congruent subtests of the Stroop Test (r=-0.85, P=0.002), a similar trend was
      seen in the left caudate (r=-0.60, P=0.07). Similar correlation was not detected
      in the putamen. The present findings provide evidence that the decreased
      dopaminergic function in the right caudate nucleus is related to the impaired
      performance in tests sensitive to frontal lobe function in patients at an early
      stage of PD and with no antiparkinsonian medication.

PMID- 11567784
TI  - Effect of anoxia and adenosine on cerebral blood flow in the leopard frog (Rana
      pipiens).
AB  - The effect of anoxia on cerebral blood velocity (CBV) on the dorsal surface of
      telencephalon was examined in the leopard frog, Rana pipiens, using a
      stereomicroscope. During exposure to anoxia, a transient 228% increase in CBV
      velocity was seen after 20 min, but CBV fell back to basal values after a further
      20 min of anoxia. Topical application of 50 microM adenosine during normoxia
      caused a 52% increase in CBV, while 250 microM adenosine caused no further
      increase. At both concentrations, the effect was completely inhibited by the
      adenosine receptor blocker aminophylline (250 microM). Superfusing the brain with
      aminophylline during anoxia did not affect the anoxia-induced increase in CBV. We
      conclude that adenosine can stimulate CBV in R. pipiens. However, unlike in other
      anoxia-tolerant animals, adenosine seems not to be a main mediator of the anoxia
      induced increase in CBV in the frog.

PMID- 11567785
TI  - Functional expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid receptors precedes the development of cholinergic phenotype in embryonic rat
      septal cells in culture.
AB  - We examined the development of cholinergic neuronal functions and alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) responses in cultured
      embryonic rat septal cells. Choline acetyltransferase activity was increased from
      4 to 6 days in culture and reached a plateau at day 8. Acetylcholine release was
      increased from 6 to 8 days in culture. AMPA-induced increase in intracellular
      Ca(2+) level was observed at 3 days in culture and most of the AMPA-responsive
      cells coincided with high-K(+) responsive cells. These results suggest that
      cholinergic neurons develop their neuronal functions about 8 days under cultured
      conditions, and functional expression of AMPA receptors precedes the cholinergic
      functional development.

PMID- 11567786
TI  - Differences in event-related and induced EEG patterns in the theta and alpha
      frequency bands related to human emotional intelligence.
AB  - High (emotional intelligence scores (EIQ)=120) and average emotional intelligent
      individuals (EIQ=89) were solving tasks from an emotional intelligence test while
      their electroencephalogram was recorded. Significant differences relating to
      emotional intelligence were observed in induced and event related band power in
      the theta (4.4-6.4 Hz), lower-2 alpha (8.4-10.4 Hz), and upper alpha band (10.4
      12.4 Hz). High emotional intelligent individuals displayed less desynchronization
      in the upper alpha band, as well as more left hemispheric theta
      desynchronization. Further a significant positive correlation between the mean
      frequency and emotional intelligence was observed. The results are similar to
      those reported for verbal and performance components of general intelligence.

PMID- 11567787
TI  - Human elbow joint torque is linearly encoded in electromyographic signals from
      multiple muscles.
AB  - When the central nervous system (CNS) develops a muscular activation pattern to
      accomplish a particular isometric task, it clearly uses information concerning
      the external task requirements. These task requirements serve as inputs to neural
      transformations that output muscular activations. However, the nature of the
      inputs is not exactly known. Electromyographic (EMG) signals from eight muscles
      spanning the human elbow, as well as the total joint torque, were collected
      during a submaximal isometric flexion/extension task at a single joint angle. The
      EMG data, without any torque information, were subjected to principal components
      analysis. We found that 98% of EMG data variation could be described by two
      principal components the first resembled the joint torque and the second
      resembled the sum of the EMG signals from all eight muscles. The findings suggest
      that the CNS encodes these two quantities during isometric tasks.

PMID- 11567788
TI  - Functional role of inducible nitric oxide synthase on mouse colonic motility.
AB  - A possible functional role of inducible isoform of nitric oxide synthase (iNOS)
      was explored in vitro on the motility of mouse distal colon. Using an isotonic -
      non-isovolumic technique, peristaltic activity and video images of the external
      wall of colonic segments were recorded before and after addition to the medium of
      Aminoguanidine (AG) and N-(3-(aminomethyl)benzyl) acetamidine (W1400) [10(-7) M
      10(-4) M], two iNOS inhibitors. AG and W1400 induced an hyperexcitability of
      visceral smooth muscle characterised by an increase of basal tone and spontaneous
      phasic activity. As a consequence of these effects, the peristaltic activity
      declined and disappeared at the highest concentrations. These findings indicated
      a removal of inhibitory action performed by NO synthesised by iNOS in the colonic
      segment. The implications of results are discussed in term of tonic relaxation of
      intestinal smooth muscle to allow intraluminal content accommodation.

PMID- 11567789
TI  - Cellular expression of functional chemokine receptor CCR5 and CXCR4 in human
      embryonic neurons.
AB  - In the present study we analysed expression of the chemokine receptors CCR5 and
      CXCR4 in human embryonic neurons. Both receptors were detected in neurons from
      primary cultures by immunofluorescence and confocal laser microscopy analysis.
      Both CCR5 and CXCR4 were mainly located inside the cell in the neuronal cell body
      and processes. In addition, neurons synthesised CCR5 and CXCR4 transcripts, as
      demonstrated by reverse transcription-polymerase chain reaction. Stimulation with
      the CCR5 and the CXCR4 agonists increased [Ca(2+)](i) in embryonic neurons,
      indicating that CXCR4 and CCR5 were functional at the neuronal surface. The
      inhibitory effect of pertussis toxin demonstrated that G(i)alpha protein is
      involved in chemokine receptor activation. The fact that chemokine receptors are
      expressed at embryonic stage in neurons reinforces the idea that chemokines might
      be cues for neuron pathfinding during brain ontogeny.

PMID- 11567790
TI  - Reticular premotor neurons projecting to both facial and hypoglossal nuclei
      receive trigeminal afferents in rats.
AB  - The distribution of premotor neurons projecting to motor nuclei of both the VIIth
      (VII) and XIIth (XII) nerves was examined in the pontomedullary reticular
      formation (RF) of the rat by using retrograde double labeling. After injection of
      two different tracers in the VII and the XII, most of the double labeled neurons
      were found caudally in the dorsal RF whereas rostrally they were located in the
      ventral RF. In some experiments, additional injections of an anterograde tracer
      were made in the sensory trigeminal nuclei. Anterogradely labeled trigeminal
      boutons were found in contact with retrogradely double labeled neurons throughout
      the pontomedullary RF. These neurons were mainly encountered ventral to the
      trigeminal motor nucleus and dorsal to the VII. Functionally, this region is
      known to be involved in eye protection mechanisms.

PMID- 11567791
TI  - Effect of noradrenergic denervation of medial prefrontal cortex and dentate gyrus
      on recovery after sleep deprivation in the rat.
AB  - The noradrenergic-locus coeruleus (LC) system has a regulatory influence on
      forebrain neuronal networks. We have previously shown that the amygdala is
      strongly implicated in the mechanism of rebound seen after a 10 h sleep
      deprivation (SD). In the present study, our objective was to determine whether
      the medial prefrontal cortex and dentate gyrus (DG) which receive an important
      innervation from the LC, play a role in the rebound mechanisms. We found that
      microinjection of the specific noradrenergic neurotoxin, N-(2-chloroethyl)-N
      ethyl-2-bromobenzylamine, into these regions had no effect on the increase in
      paradoxical sleep duration seen after SD, suggesting that noradrenergic (NA)
      innervation of the prefrontal cortex and DG are not involved in sleep rebound
      regulation.

PMID- 11567792
TI  - Possible involvement of amino acid transporters on S-nitroso-cysteine-induced
      inhibition of arachidonic acid release in PC12 cells.
AB  - Previously, we proposed that S-nitroso-cysteine (SNC) was incorporated via the L
      type-like amino acid transporters in rat brain slices. In PC12 cells (rat
      neuronal cell line), SNC inhibited [(3)H]arachidonic acid (AA) release induced by
      mastoparan (wasp venom peptide). We investigated the involvement of amino acid
      transporters on SNC-induced inhibition of [(3)H]AA release in PC12 cells. SNC
      inhibited mastoparan-stimulated [(3)H]AA release in a concentration-dependent
      manner in normal Na(+)- and low Na(+)-containing buffer. The inhibitory effect of
      0.6 mM SNC in low Na(+) buffer decreased by 10 mM L-leucine, L-phenylalanine, L
      methionine and L-cysteine. In contrast, L-alanine, L-threonine, L-valine or L
      isoleucine showed very limited effects. Addition of L-leucine and L
      phenylalanine, but not L-alanine or L-valine, also decreased the inhibitory
      effect of SNC on ionomycin/Na(3)VO(4)-stimulated [(3)H]AA release in normal Na(+)
      buffer. These findings suggest that SNC is incorporated via the amino acid
      transporters and inhibits AA release in PC12 cells.

PMID- 11567793
TI  - Systemic administration of a water-soluble hexasulfonated C(60) (FC(4)S) reduces
      cerebral ischemia-induced infarct volume in gerbils.
AB  - Buckminsterfullerence and its derivatives have recently been shown to exhibit
      considerable in vivo biological activities. A water-soluble hexasulfonated C(60)
      (FC(4)S) has been shown to protect against oxidative stress. Neuroprotective
      effects of FC(4)S were investigated in the present study. Focal cerebral ischemia
      was produced by a permanent occlusion of the right middle cerebral artery in
      gerbils. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride
      transcardiac perfusion 24 h after cerebral ischemia. Chronic pretreatment of
      FC(4)S (0.5 and 5.0 mg/kg/day, intraperitoneally for 2 weeks) significantly
      reduced the infarct volume (by 42% and 68%, respectively) when compared to that
      of the control group. Results revealed that chronic pretreatment of FC(4)S may
      protect the brain against focal cerebral ischemia.

PMID- 11567794
TI  - Effect of mercaptoethylguanidine scavengers of peroxynitrite on the development
      of experimental allergic encephalomyelitis in PLSJL mice.
AB  - Peroxynitrite has been implicated in the pathogenesis of multiple sclerosis and
      its animal counterpart experimental allergic encephalomyelitis (EAE). Here we
      have examined the effects of the novel peroxynitrite scavengers,
      mercaptoethylguanidine (MEG) and guanidinoethyldisulphide (GED), on the
      development of EAE. Both MEG and GED delayed EAE onset and decreased the number
      of animals displaying disease signs. However, when EAE developed, its severity
      was not significantly abrogated by drug administration. These results suggest
      that while MEG and GED protect against the induction phase of EAE, they do not
      prevent disease progression. This may be due to the inability of MEG and GED to
      efficiently scavenge peroxynitrite or result from their capacity to inhibit
      inducible nitric oxide synthase. Therefore, the development of more potent and
      selective scavengers of peroxynitrite is necessary for use in EAE.

PMID- 11567795
TI  - Inhibition of rat PC12 cell calpain activity by glutathione, oxidized glutathione
      and nitric oxide.
AB  - Calpain, a calcium activated neutral protease, is involved in mediating
      neurotoxicity resulting from conditions of oxidative stress and free radical
      formation, such as hypoxia and ischemia. Nitric oxide (NO) may also be involved
      in modulating the cytotoxic effects of oxidative stress. We investigated the
      roles of reduced glutathione (GSH), oxidized glutathione (GSSG), and NO in
      modulating calpain activity in PC12 cells. Cell extracts were treated with GSSG,
      GSH, or the NO-donor S-nitroso-N-acetylpenicillamine. Calpain activity was
      determined by means of a fluorescent assay. Non-linear regression analysis was
      used to determine the type of inhibition (competitive, uncompetitive, or non
      competitive). GSH displayed uncompetitive inhibition, with K(i)=7.0+/-2.0 mM
      (Mean+/-SEM) while GSSG exhibited competitive inhibition with K(i)=2.5+/-0.3 mM.
      NO was an irreversible inhibitor of calpain activity. These results suggest that
      both GSH and GSSG may be important physiological modulators of calpain activity.

PMID- 11567796
TI  - Sphingomyelinase but not ceramide induces nitric oxide synthase expression in rat
      brain microglia.
AB  - Microglia, brain inflammatory cells, are activated in injured brain and function
      similar to macrophages. The activated microglia produce nitric oxide (NO), a
      major toxic substance from these cells, by inducing expression of inducible NO
      synthase (iNOS). In this study, we found that sphingomyelinase (SMase) alone
      induced NO release/iNOS mRNA expression in cultured rat brain microglia. On the
      contrary to SMase, however, membrane-permeable c2-ceramide had little effect on
      NO release/iNOS mRNA expression. Fumonisin B1, an inhibitor of de novo synthesis
      of ceramide, did not reduce lipopolysaccharide (LPS)-induced NO release. However,
      neither SMase nor c2-ceramide enhanced LPS- or Abeta (25-35)-induced NO
      release/iNOS mRNA expression.

PMID- 11567797
TI  - Expression of voltage-gated calcium channel subunits in rat dorsal root ganglion
      neurons.
AB  - In the present study, we have used in situ hybridisation to examine the
      distribution of calcium channel subunits in rat dorsal root ganglion (DRG)
      neurons. Within DRG neurons, the calcium channel alpha subunit mRNAs alpha(1A),
      alpha(1B), alpha(1C), alpha(1D), alpha(1E), alpha(1I) and alpha(1S) were readily
      detected in small (<25 microm), medium (25-45 microm) and large (>45 microm)
      diameter neurons. alpha(1F) was present at very low levels in these neurons
      whilst alpha(1G) was virtually undetectable. The calcium channel auxiliary
      subunits alpha(2)delta(1) and alpha(2)delta(2) showed a complementary pattern of
      distribution to that of alpha(2)delta(3) in DRG neurons. alpha(2)delta(1) and
      alpha(2)delta(2) transcripts were expressed predominantly in small c-type sensory
      neurons and were present at lower levels in large Abeta-type sensory neurons. In
      contrast, alpha(2)delta(3) mRNA was present in high quantities in the large
      diameter cells but was expressed at lower levels in small-diameter neurons of the
      DRG. The present study provides an insight into the molecular profile of calcium
      channel alpha(1) and alpha(2)delta subunits in the neurons responsible for
      transmitting sensory information.

PMID- 11567798
TI  - Hydrogen peroxide induces transient dephosphorylation of tau protein in cultured
      rat oligodendrocytes.
AB  - Oxidative stress is a major mediator of neurodegeneration. In this study, we
      tested the effects of oxidative stress induced by a brief exposure to hydrogen
      peroxide (H(2)O(2)) on the phosphorylation state of the tau protein in
      oligodendrocytes (OL). Primary oligodendrocyte cultures prepared from newborn rat
      brains were exposed to millimolar concentrations of H(2)O(2) for up to 15 min,
      and then incubated in normal medium for up to 12 h. The treatment caused
      morphological degeneration of OL characterized by the loss of cellular processes
      apparent approximately 3 h after H(2)O(2) exposure. The morphological
      degeneration was preceded by a profound dephosphorylation of tau protein revealed
      by immunoblot using monoclonal tau-1 antibody that recognizes the
      dephosphorylated epitope. The dephosphorylated form increased dramatically during
      H(2)O(2) exposure, peaked after 2 h of post-exposure, and returned to the
      baseline level within 12 h. Total tau protein levels were not changed in the
      course of the experiment as judged by immunoblotting with phosphorylation
      insensitive tau-5 and 46-1 monoclonal antibodies. Our finding demonstrates that
      oxidative stress induces a rapid but transient dephosphorylation of tau protein
      that may underlie morphological degeneration of OL.

PMID- 11567799
TI  - Are all consents really informed?

PMID- 11567800
TI  - What is research?

PMID- 11567801
TI  - Dosimetric predictors of radiation esophagitis in patients treated for non-small
      cell lung cancer with carboplatin/paclitaxel/radiotherapy.
AB  - PURPOSE: To establish dosimetric predictors of radiation esophagitis (RE) in
      patients treated with a combination of carboplatin, paclitaxel, and radiotherapy.
      METHODS AND MATERIALS: Three-dimensional radiotherapy plans of 26 patients with
      non-small-cell lung cancer who received 50-60 Gy of radiotherapy concurrently
      with weekly administration of carboplatin (AUC 2) and paclitaxel (40-45 mg/m(2))
      were reviewed in conjunction with RE. The factors analyzed included the
      following: percentages of organ volumes receiving >40 Gy (V40), >45 Gy (V45), >50
      Gy (V50), and >55 Gy (V55); the length of esophagus (total circumference) treated
      with >40 Gy (LETT40), >45 Gy (LETT45), >50 Gy (LETT50), and >55 Gy (LETT55); the
      maximum dose in the esophagus (Dmax); and the mean dose in the esophagus (Dmean).
      Data were obtained on the basis of superposition algorithm. RESULTS: All factors
      except Dmax showed statistical correlation with RE. Good correlations were shown
      between RE and LETT45 (rho = 0.714) and V45 (rho = 0.686). CONCLUSIONS: LETT45
      and V45 appear to be useful dosimetric predictors of RE. It is also suggested
      that Dmax does not predict RE.

PMID- 11567802
TI  - Can short-term administration of dexamethasone abrogate radiation-induced acute
      cytokine gene response in lung and modify subsequent molecular responses?
AB  - PURPOSE: To investigate the effects of short-term administration of dexamethasone
      (DEX) on radiation-induced responses in the mouse lung, focusing on expression of
      pro-inflammatory cytokine and related genes. METHODS AND MATERIALS: At indicated
      times after thoracic irradiation and/or drug treatment, mRNA expression levels of
      cytokines (mTNF-alpha, mIL-1 alpha, mIL-1 beta, mIL-2, mIL-3, mIL-4, mIL-5, mIL
      6, mIFN-gamma) and related genes in the lungs of C3H/HeN mice were measured by
      RNase protection assay. RESULTS: Radiation-induced pro-inflammatory cytokine mRNA
      expression levels in lung peak at 6 h after thoracic irradiation. DEX (5 mg/kg)
      suppresses both basal cytokine mRNA levels and this early response when given
      immediately after irradiation. However, by 24 h, in mice treated with DEX alone
      or DEX plus radiation, there was a strong rebound effect that lasted up to 3
      days. Modification of the early radiation-induced response by DEX did not change
      the second wave of cytokine gene expression in the lung that occurs at 1 to 2
      weeks, suggesting that early cytokine gene induction might not determine
      subsequent molecular events. A single dose of DEX attenuated, but did not
      completely suppress, increases in cytokine mRNA levels induced by
      lipopolysaccharide (2.5 mg/kg) treatment, but, unlike with radiation, no
      significant rebound effect was seen. Five days of dexamethasone treatment in the
      pneumonitic phase also inhibited pro-inflammatory cytokine gene expression and,
      again, there was a rebound effect after withdrawal of the drug. CONCLUSIONS: Our
      findings suggest that short-term use of dexamethasone can temporarily suppress
      radiation-induced pro-inflammatory cytokine gene expression, but there may be a
      rebound after drug withdrawal and the drug does little to change the essence and
      course of the pneumonitic process.

PMID- 11567803
TI  - Detection of lung tumor movement in real-time tumor-tracking radiotherapy.
AB  - PURPOSE: External radiotherapy for lung tumors requires reducing the uncertainty
      due to setup error and organ motion. We investigated the three-dimensional
      movement of lung tumors through an inserted internal marker using a real-time
      tumor-tracking system and evaluated the efficacy of this system at reducing the
      internal margin. METHODS AND MATERIALS: Four patients with lung cancer were
      analyzed. A 2.0-mm gold marker was inserted into the tumor. The real-time tumor
      tracking system calculates and stores three-dimensional coordinates of the marker
      30 times/s. The system can trigger the linear accelerator to irradiate the tumor
      only when the marker is located within the predetermined "permitted dislocation."
      The value was set at +/-1 to +/-3 mm according to the patient's characteristics.
      We analyzed 10,413-14,893 data sets for each of the 4 patients. The range of
      marker movement during normal breathing (beam-off period) was compared with that
      during gated irradiation (beam-on period) by Student's t test. RESULTS: The range
      of marker movement during the beam-off period was 5.5-10.0 mm in the lateral
      direction (x), 6.8-15.9 mm in the craniocaudal direction (y) and 8.1-14.6 mm in
      the ventrodorsal direction (z). The range during the beam-on period was reduced
      to within 5.3 mm in all directions in all 4 patients. A significant difference
      was found between the mean of the range during the beam-off period and the mean
      of the range during the beam-on period in the x (p = 0.007), y (p = 0.025), and z
      (p = 0.002) coordinates, respectively. CONCLUSION: The real-time tumor-tracking
      radiotherapy system was useful to analyze the movement of an internal marker.
      Treatment with megavoltage X-rays was properly given when the tumor marker moved
      into the "permitted dislocation" zone from the planned position.

PMID- 11567804
TI  - Relating radiation-induced regional lung injury to changes in pulmonary function
      tests.
AB  - PURPOSE: To determine whether the sum of radiotherapy (RT)-induced reductions in
      regional lung perfusion is quantitatively related to changes in global lung
      function as assessed by reductions in pulmonary function tests (PFTs). METHODS
      AND MATERIALS: Two hundred seven patients (70% with lung cancer) who received
      incidental partial lung irradiation underwent PFTs (forced expiratory volume in 1
      s and diffusion capacity for carbon monoxide) before and repeatedly after RT as
      part of a prospective clinical study. Regional lung function was serially
      assessed before and after RT by single photon emission computed tomography
      perfusion scans. Of these, 53 patients had 105 post-RT evaluations of changes in
      both regional perfusion and PFTs, were without evidence of intrathoracic disease
      recurrence that might influence regional perfusion and PFT findings, and were not
      taking steroids. The summation of the regional functional perfusion changes were
      compared with changes in PFTs using linear regression analysis. RESULTS: Follow
      up ranged from 3 to 86 months (median 19). Overall, a significant correlation was
      found between the sum of changes in regional perfusion and the changes in the
      PFTs (p = 0.002-0.24, depending on the particular PFT index). However, the
      correlation coefficients were small (r = 0.16-0.41). CONCLUSIONS: A statistically
      significant correlation was found between RT-induced changes in regional function
      (i.e., perfusion) and global function (i.e., PFTs). However, the correlation
      coefficients are low, making it difficult to relate changes in perfusion to
      changes in the PFT results. Thus, with our current techniques, the prediction of
      changes in perfusion alone does not appear to be sufficient to predict the
      changes in PFTs accurately. Additional studies to clarify the relationship
      between regional and global lung injury are needed.

PMID- 11567805
TI  - An implementation strategy for IMRT of ethmoid sinus cancer with bilateral
      sparing of the optic pathways.
AB  - PURPOSE: To develop a protocol for the irradiation of ethmoid sinus cancer, with
      the aim of sparing binocular vision; of developing a strategy of intensity
      modulated radiation therapy (IMRT) planning that produces dose distributions that
      (1) are consistent with the protocol prescriptions and (2) are deliverable by
      static segmental IMRT techniques within a 15-minute time slot; of fine tuning the
      implementation strategy to a class solution approach that is sufficiently
      automated and efficient, allowing routine clinical application; of reporting on
      the early clinical implementation involving 11 patients between February 1999 and
      July 2000. patients and methods: Eleven consecutive T1-4N0M0 ethmoid sinus cancer
      patients were enrolled in the study. For Patients 1-8, a first protocol was
      implemented, defining a planning target volume prescription dose of 60 to 66 Gy
      in 30-33 fractions and a maximum dose (Dmax) of 50 Gy to optic pathway structures
      and spinal cord and limit of 60 Gy to brainstem. For Patients 9-11, an adapted
      (now considered mature) protocol was implemented, defining a (planning target
      volume) prescription dose of 70 Gy in 35 fractions and a Dmax to optic pathway
      structures and brainstem of 60 Gy and to spinal cord of 50 Gy. RESULTS: The class
      solution-directed strategy developed during this study reduced the protocol
      translation process from a few days to about 2 hours of planner time. The mature
      class solution involved the use of 7 beam incidences (20-37 segments), which
      could be delivered within a 15-minute time slot. Acute side effects were limited
      and mild. None of the patients developed dry eye syndrome or other visual
      disturbances. The follow-up period is too short for detection of retinopathy or
      optic nerve and chiasm toxicity. CONCLUSION: Conventional radiotherapy of ethmoid
      sinus tumors is associated with serious morbidity, including blindness. We
      hypothesize that IMRT has the potential to save binocular vision. The dose to the
      optic pathway structures can be reduced selectively by IMRT. Further enrollment
      of patients and longer follow-up will show whether the level of reduction tested
      by the clinical protocol is sufficient to save binocular vision. An adaptive
      strategy of IMRT planning was too inefficient for routine clinical practice. A
      class solution-directed strategy improved efficiency by eliminating human trial
      and error during the IMRT planning process.

PMID- 11567806
TI  - The benefits and pitfalls of ipsilateral radiotherapy in carcinoma of the
      tonsillar region.
AB  - PURPOSE: Ipsilateral techniques designed to restrict treatment to the primary
      tumor and neck on the same side have been used in selected cases of cases of
      carcinoma of the tonsillar region at our institution for many years. The primary
      purpose of this study is to evaluate the risk of failure in the opposite neck in
      cases selected for unilateral radiotherapy over a 21-year period. METHODS AND
      MATERIALS: Ipsilateral radiotherapy techniques were used in 228 of 642 patients
      with carcinoma of the tonsillar region from 1970 to 1991. Local control, regional
      lymph-node control (including contralateral failure), and survival were
      calculated for different degrees of tumor extent treated with these techniques.
      RESULTS: Mean follow-up was 7 years. Cases tended to be T1 and T2, with N0
      disease. The 3-year actuarial local control rate was 77% and cause-specific
      survival was 76%. Opposite neck failure was seen in 8 patients (crude rate of
      3.5%). In the earlier period of the study, primary coverage was problematic in a
      proportion of cases and resulted in higher rates of local failure. CONCLUSION:
      Appropriately selected cases of carcinoma of the tonsil show minimal risk of
      failure in the opposite neck with ipsilateral techniques. Patients should undergo
      computed tomography planning to ensure adequate target coverage.

PMID- 11567807
TI  - Different risks of symptomatic brain necrosis in NPC patients treated with
      different altered fractionated radiotherapy techniques.
AB  - PURPOSE: To report our observation of excessive temporal lobe necrosis in
      nasopharyngeal carcinoma (NPC) patients treated with 160 cGy b.i.d. radiotherapy
      technique. During the same period, patients treated with 120 cGy b.i.d. have not
      shown a similar tendency. Our experience may be useful for designing
      unconventional radiotherapy regimens for NPC patients. METHODS AND MATERIALS:
      During the period from October 1991 to January 1998, 81 M0, previously untreated
      NPC patients completed altered fractionated radiotherapy. Seventy patients were
      treated with the hyperfractionated technique, and 11 were treated using the
      accelerated-hyperfractionated scheme. Hyperfractionated radiotherapy was
      delivered using 120 cGy b.i.d. separated by 6-h intervals throughout the course.
      A minimum tumor dose of 8000 cGy was the standard dose over an 8-week period.
      With the accelerated-hyperfractionated scheme, 160 cGy was given twice daily,
      also with an interval of 6 h. The minimum tumor dose ranged between 6840 and 7640
      cGy, with 7 of the 11 patients receiving 7000 cGy. The arrangement of portals was
      the same for both regimens. The follow-up period for patients alive was from 32
      to 102 months with a median of 61 months for the hyperfractionated patients. For
      the accelerated-hyperfractionated group, it ranged from 67 to 82 months with a
      median of 72 months. No patient was lost to follow-up. RESULTS: At the time of
      analysis, 49 of the 70 patients in the hyperfractionated group were alive. In the
      accelerated group, 8 of the 11 patients were alive. The estimated radiation dose
      to the temporal lobe for the hyperfractionated group was 6000-7440 cGy with a
      median of 7080 cGy. For the accelerated-hyperfractionated group, the dose range
      was 4480-6700 cGy with a median of 6400 cGy. Of the 70 patients treated with
      hyperfractionated radiotherapy, none developed symptomatic brain necrosis,
      despite the higher total dose to the temporal lobe in general. In contrast, 3 of
      the 11 (27%) patients irradiated using the accelerated-hyperfractionated regimen
      suffered from temporal lobe necrosis at 16, 19, and 40 months after completion of
      radiotherapy. CONCLUSION: An excessive incidence of temporal lobe necrosis was
      noted when an accelerated-hyperfractionated regimen with 160 cGy b.i.d. was used
      in NPC patients with a median brain dose of 6400 cGy. There has been no such
      event in patients treated using a hyperfractionated regimen with 120 cGy and a
      median brain dose of 7000 cGy. The real causes of this discrepancy are not known.
      However, a high sensitivity of the human brain to a change in fraction size may
      play a role.

PMID- 11567808
TI  - Elevated tumor lactate concentrations predict for an increased risk of metastases
      in head-and-neck cancer.
AB  - PURPOSE: Hypoxia shifts the balance of cellular energy production toward
      glycolysis with lactate generation as a by-product. Quantitative bioluminescence
      imaging allows for the quantitation of lactate concentrations in individual
      tumors. We assessed the relationship between pretreatment tumor lactate
      concentrations and subsequent development of metastatic disease in patients with
      newly diagnosed head-and-neck cancer. METHODS AND MATERIALS: At the time of
      biopsy of the primary site, a separate specimen was taken and flash-frozen for
      subsequent quantitation of lactate concentration using a luciferase
      bioluminescence technique. The two-dimensional spatial distribution of the
      bioluminescence intensity within the tissue section was registered directly using
      a microscope and an imaging photon counting system. Photon intensity was
      converted to distributions of volume-related tissue concentrations (micromol per
      gram wet weight). Treatment consisted of either surgery and postoperative
      radiotherapy or primary radiotherapy, based on presenting disease stage and
      institutional treatment policies. The subsequent development of metastatic
      disease constituted the primary clinical endpoint. RESULTS: Biopsies obtained
      from 40 patients were evaluable in 34. The larynx was the most frequent primary
      site (n = 25). Other sites included oropharynx (n = 5), hypopharynx (n = 3), and
      oral cavity (n = 1). Most patients (74%) presented with an advanced stage T3 or
      T4 primary tumor. Nodal involvement was present in 19 (54%) patients. The median
      tumor lactate concentration was 7.1 micromol/g. Tumors were classified as having
      either low or high lactate concentrations according to whether these values were
      below or above the median. The median follow-up time for surviving patients is 27
      months. Two-year actuarial survival was 90% for patients with low-lactate
      concentration tumor vs. 35% for patients with high-lactate-concentration
      primaries (<0.0001). Two-year metastasis-free survival was adversely influenced
      by high tumor lactate concentrations (90% vs. 25%, p < 0.0001). The median
      lactate concentration for tumors that subsequently metastasized was 12.9
      micromol/g vs. 4.8 micromol/g for patients who remained continuously free of
      disease (p < 0.005). Lactate concentration was not correlated with presenting T
      stage or N stage. DISCUSSION: Elevated tumor lactate concentrations are
      associated with the subsequent development of nodal or distant metastases in head
      and-neck cancer patients. This more aggressive malignant phenotype is probably
      associated with hypoxia-mediated radioresistance and the upregulation of
      metastasis-associated genes.

PMID- 11567809
TI  - Interstitial low-dose-rate brachytherapy as a salvage treatment for recurrent
      head-and-neck cancers: long-term results.
AB  - PURPOSE: Recurrent cancers of the head and neck within previously irradiated
      volume pose a serious therapeutic challenge. This study evaluates the response
      and long-term tumor control of recurrent head-and-neck cancers treated with
      interstitial low-dose-rate brachytherapy. METHODS AND MATERIALS: Between 1979 and
      1997, 220 patients with prior radiation therapy with or without surgery for
      primary tumors of the head and neck were treated for recurrent disease or new
      primary tumors located within previously irradiated volumes. A majority of these
      patients had inoperable diseases with no distant metastasis. There were 136 male
      and 84 female patients, and median age was 56 years. All patients had previously
      received radiation therapy as the primary treatment or adjuvant treatment
      following surgery, with a median dose of 57.17 cGy (range, 39-74 cGy). The
      salvage brachytherapy consisted of a low-dose-rate, afterloading Iridium(192)
      implant, which delivered a median minimum tumor dose of 53 Gy to a mean tumor
      volume of 68.75 cm(2). Sixty percent of the patients also received interstitial
      hyperthermia, and 40% received concurrent chemotherapy as a radiosensitizing and
      potentiating agent. RESULTS: At a minimum 6-month follow-up, local tumor control
      was achieved in 77% (217/282) of the implanted tumor sites. The 2, 5, and 10-year
      disease-free actuarial survival rates for the entire group were 60%, 33%, and
      22%, respectively. The overall survival rate for the entire group at 5 years was
      21.7%. Moderate to severe late complications occurred in 27% of the patients.
      CONCLUSION: It has been estimated that approximately 20-30% of head-and-neck
      cancer patients undergoing definitive radiation therapy have recurrence within
      the initial treatment volume. Furthermore, similar percentages of patients who
      survive after successful irradiation develop new primary tumors of the head and
      neck or experience metastatic neck disease. A majority of such patients cannot be
      treated with a repeat course of external beam irradiation because of limited
      normal tissue tolerance, leading to unacceptable morbidity. However, in a select
      group of these patients, salvage interstitial brachytherapy may play an important
      role in providing patients with durable palliation and tumor control, as well as
      a chance for cure.

PMID- 11567810
TI  - Treatment of rectal adenocarcinoma with endocavitary and external beam
      radiotherapy: results for 199 patients with localized tumors.
AB  - PURPOSE: Endocavitary radiation (RT) provides a conservative alternative to
      proctectomy. Although most suitable for small, mobile lesions, patients with less
      favorable tumors are often referred if they are poor surgical candidates. Knowing
      the extent to which radiation can control such tumors can be an important factor
      in making clinical decisions. METHODS AND MATERIALS: One hundred ninety-nine
      patients, who received endocavitary RT with or without external beam RT (EBRT)
      during 1981 through 1995, were followed for disease status for a median of 70
      months, including deaths from intercurrent causes. In the early years of the
      study, 21 patients were treated with endocavitary RT alone, the remainder of the
      patients received pelvic EBRT (usually 45 Gy in 25 fractions) 5-7 weeks before
      endocavitary RT. RESULTS: Overall, 141 patients (71%) had local control with RT
      alone. Salvage surgery rendered an additional 20 patients disease free, for an
      ultimate local control rate of 81%. On multivariate analysis for local control
      (excluding surgical salvage), the most significant factors were mobility to
      palpation, use of EBRT, and whether pretreatment debulking of all macroscopic
      disease had been done (generally a piecemeal, nontransmural procedure). Of 77
      cases staged by transrectal ultrasonography, the local control rate with RT alone
      was 100% for uT1 lesions, 85% (90% with no evidence of disease after salvage) for
      freely mobile uT2 lesions, and 56% (67% with no evidence of disease after
      salvage) for uT3 lesions and uT2 lesions that were not freely mobile.
      CONCLUSIONS: Patients with small mobile tumors that are either uT1 or have only a
      scar after debulking achieve excellent local control with endocavitary RT. About
      15% of mobile uT2 tumors fail RT; therefore, careful follow-up is critical. Small
      uT3 tumors are appropriate for this treatment only if substantial
      contraindications to proctectomy are present.

PMID- 11567811
TI  - Ten years of preoperative chemoradiation for extraperitoneal T3 rectal cancer:
      acute toxicity, tumor response, and sphincter preservation in three consecutive
      studies.
AB  - PURPOSE: To compare acute toxicity, tumor response, and sphincter preservation in
      three schedules of concurrent chemoradiation in resectable transmural and/or node
      positive extraperitoneal rectal cancer. PATIENTS AND METHODS: Between 1990 and
      1999, 163 consecutive patients were treated according to the following combined
      modalities: FUMIR: between 1990 and 1995, 83 patients were treated with bolus
      i.v. mitomycin C (MMC), 10 mg/m(2) day 1, plus 24-h continuous infusion i.v. 5
      fluorouracil (5-FU) 1,000 mg/m(2) days 1-4, and concurrent external beam
      radiotherapy (37.8 Gy). PLAFUR-4: between 1995 and 1998, 40 patients were treated
      with cisplatin (c-DDP) 60 mg/m(2) given as slow infusion (1-4 h) on days 1 and
      29, plus 24-h continuous infusion i.v. 5-FU 1,000 mg/m(2), days 1-4 and 29-32
      with concurrent external-beam radiotherapy (50.4 Gy). PLAFUR-5: between 1998 and
      1999, 40 patients were treated with c-DDP 60 mg/m(2) given as slow infusion
      (during 1-4 h) on days 1 and 29, plus 24-h continuous infusion i.v. 5-FU 1,000
      mg/m(2), days 1-5 and 29-33 with concurrent external-beam radiotherapy (50.4 Gy).
      RESULTS: Grade > or = 3 acute toxicity occurred in 14%, 5%, and 17% of patients
      treated in the FUMIR, PLAFUR-4, and PLAFUR-5 studies, respectively (p = 0.201).
      In the FUMIR, PLAFUR-4, and PLAFUR-5 studies, clinical response rate was 77%,
      70%, and 83%, respectively. Tumor downstaging occurred in 57%, 68%, and 58% of
      patients, respectively. Pathologic complete response was recorded in 9% (FUMIR),
      23% (PLAFUR-4), and 20% (PLAFUR-5) of patients. Sphincter-preserving surgery was
      feasible in 44% (FUMIR), 40% (PLAFUR-4), and 61% (PLAFUR-5) of patients having a
      distance between the anal-rectal ring and the lower pole of the tumor of 0-30 mm,
      and in 95%, 100%, and 100%, respectively, in those having a distance of 31-50 mm.
      Comparing FUMIR vs. PLAFUR, the clinical response rate was similar in the two
      series: a partial response was observed in 62/81 (77%) patients with FUMIR
      treatment, and in 61/80 (76%) patients with PLAFUR treatment. Tumor downstaging
      was observed in 46/81 (57%) patients and in 50/80 (68%) patients, respectively.
      The pathologic complete response rate was statistically higher in the PLAFUR
      series: 7/81 (9%) patients with FUMIR treatment and 17/80 (21%) patients with
      PLAFUR treatment (p = 0.04). Major downstaging (pT0+ pTmic+ pT1) in the FUMIR
      group was reported in 12/81 (15%) patients versus 31/80 (39%) patients in the
      PLAFUR group (p = 0.0006). The anal sphincter was preserved in 63/81 (78%)
      patients with FUMIR treatment and in 69/80 (86%) patients with PLAFUR treatment.
      The perioperative morbidity was statistically lower with PLAFUR: a perioperative
      morbidity was experienced by 20/81 (25%) patients with FUMIR treatment and by
      9/80 (11%) patients with PLAFUR treatment (p = 0.042). CONCLUSION: In our
      experience, higher radiation dose (50.4 Gy vs. 37.8 Gy), a second course of
      concurrent 5-FU, and the use of c-DDP instead of MMC improved the pathologic
      response rate without increasing acute toxicity and perioperative morbidity. The
      use of 5-FU 5-day infusion (PLAFUR-5) resulted in higher toxicity with a similar
      response rate compared to 4-day infusion (PLAFUR-4).

PMID- 11567812
TI  - Epithelioid sarcoma: results of conservative surgery and radiotherapy.
AB  - PURPOSE: To determine the outcome and prognostic factors for patients with
      localized epithelioid sarcoma treated with conservative surgery and radiotherapy
      (RT). METHODS AND MATERIALS: The medical records of 24 patients with
      nonmetastatic epithelioid sarcoma treated with conservative surgery and RT were
      reviewed. Preoperative RT was given to 3 patients (median 46.4 Gy) and
      postoperative RT to 21 patients (median 64.5 Gy). A local (limb-sparing) surgical
      procedure was performed in all patients. RESULTS: At a median follow-up of 131
      months, 14 patients had relapsed and 13 patients had died. The actuarial overall
      and disease-free survival rate at 10 years was 50% and 37%, respectively. Local,
      nodal, and metastatic failure occurred in 7, 4, and 10 patients, respectively,
      yielding a 10-year actuarial local, nodal, and metastatic control rate of 63%,
      81%, and 56%, respectively. Univariate analysis revealed that size < or =5 cm and
      extremity location were favorable prognostic factors for overall, disease-free,
      and metastasis-free survival. The actuarial 5-year overall, disease-free, and
      metastasis-free survival rate was 79% vs. 25% (p = 0.002), 51% vs. 13% (p =
      0.03), and 79% vs. 13% (p <0.001), respectively, for lesion size < or =5 vs. > 5
      cm. The actuarial 5-year overall, disease-free, and metastasis-free survival rate
      was 77% vs. 39% (p = 0.002), 56% vs. 0% (p = 0.01), and 78% vs. 17% (p = 0.01),
      respectively, for extremity vs. nonextremity location. Multivariate analysis of
      the factors correlating with the overall, disease-free, and metastasis-free
      survival confirmed the favorable prognostic significance of small lesion size.
      The prognostic significance of extremity location on univariate analysis was
      explained by an imbalance in the mean tumor sizes. CONCLUSIONS: Epithelioid
      sarcoma is an aggressive soft-tissue sarcoma, with high rates of local and
      distant relapse. Local control with conservative surgery and RT compares
      favorably to published surgical series. The poor outcome for tumors > or =5 cm in
      size emphasizes the need for effective systemic therapy.

PMID- 11567813
TI  - Combination of photon and proton radiation therapy for chordomas and
      chondrosarcomas of the skull base: the Centre de Protontherapie D'Orsay
      experience.
AB  - PURPOSE: Prospective analysis of local tumor control, survival, and treatment
      complications in 44 consecutive patients treated with fractionated photon and
      proton radiation for a chordoma or chondrosarcoma of the skull base. METHODS AND
      MATERIALS: Between December 1995 and December 1998, 45 patients with a median age
      of 55 years (14-85) were treated using a 201-MeV proton beam at the Centre de
      Protontherapie d'Orsay, 34 for a chordoma and 11 for a chondrosarcoma.
      Irradiation combined high-energy photons and protons. Photons represented two
      thirds of the total dose and protons one-third. The median total dose delivered
      within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70).
      RESULTS: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local
      control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively,
      and 3-year overall survival rates were 91% and 90%, respectively. Eight patients
      (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four
      patients died of tumor and 2 others of intercurrent disease. In univariate
      analysis, young age at time of radiotherapy influenced local control positively
      (p < 0.03), but not in multivariate analysis. Only 2 patients presented Grade 3
      or 4 complications. CONCLUSION: In skull-base chordomas and chondrosarcomas, the
      combination of photons with a proton boost of one-third the total dose offers an
      excellent chance of cure at the price of an acceptable toxicity. These results
      should be confirmed with a longer follow-up.

PMID- 11567814
TI  - Localized whole eye radiotherapy for retinoblastoma using a (125)I applicator,
      "claws".
AB  - PURPOSE: To treat children with retinoblastoma, who require whole eye
      radiotherapy, with a specially designed (125)I applicator that irradiates the eye
      while sparing the surrounding tissues. METHODS AND MATERIALS: Under general
      anesthesia, a pericorneal ring is attached to the 4 extraocular muscles, and 4
      appendages, each loaded with (125)I seeds, are inserted beneath the conjunctiva
      in-between each pair of muscles and attached anteriorly to the ring. Twenty-nine
      eyes were treated. Eighteen received a median dose of 28 Gy during 91 hours and
      11 received 40 Gy during 122 hours, when the relative biologic effectiveness was
      taken as 1 instead of 1.5. Six had received prior chemotherapy. RESULTS: Twenty
      four eyes were followed up for 2-157 months (median 29). Although 22 eyes
      responded, local control was achieved in 13 patients, 3 of whom required
      additional treatment for new tumors; a further 3 required additional treatment
      for tumor recurrence as well as new tumors. One of these eyes was enucleated for
      neovascular glaucoma. All 6 Group I-III eyes and 6 of 18 Group V eyes were
      retained for 2-157 months (median 39), with good vision in 10 eyes. Three
      developed cataracts 7, 8, and 12 years later, 1 of which has been removed.
      CONCLUSIONS: This is a new way of irradiating the whole eye with a minimal dose
      to the surrounding tissues. The treatment time is only 5 days. It is effective in
      Groups I-III, but only 33% of Group V eyes retained vision. No late cosmetic
      defects occurred.

PMID- 11567815
TI  - EGFR overexpression and radiation response in glioblastoma multiforme.
AB  - PURPOSE: Recent studies have suggested relative radioresistance in glioblastoma
      multiforme (GM) tumors in older patients, consistent with their shorter survival.
      Two common molecular genetic abnormalities in GM are age related: epidermal
      growth factor receptor (EGFR) overexpression in older patients and p53 mutations
      in younger patients. We tested whether these abnormalities correlated with
      clinical heterogeneity in GM response to radiation treatment. METHODS AND
      MATERIALS: Radiographically assessed radiation response (5-level scale) was
      correlated with EGFR immunoreactivity, p53 immunoreactivity, and p53 exon 5-8
      mutation status in 170 GM patients treated using 2 prospective clinical
      protocols. Spearman rank correlation and proportional-odds ordinal regression
      were used for univariate and multivariate analysis. RESULTS: Positive EGFR
      immunoreactivity predicted poor radiographically assessed radiation response (p =
      0.046). Thirty-three percent of tumors with no EGFR immunoreactivity had good
      radiation responses (>50% reduction in tumor size by CT or MRI), compared to 18%
      of tumors with intermediate EGFR staining and 9% of tumors with strong staining.
      There was no significant relationship between p53 immunoreactivity or mutation
      status and radiation response. Significant relationships were noted between EGFR
      score and older age and between p53 score or mutation status and younger age.
      CONCLUSION: The observed relative radioresistance of some GMs is associated with
      overexpression of EGFR.

PMID- 11567816
TI  - Clinical relevance of consolidation radiotherapy and other main therapeutic
      issues in primary central nervous system lymphomas treated with upfront high-dose
      methotrexate.
AB  - PURPOSE: To evaluate the optimal dose of methotrexate (MTX) and the efficacy of
      other drugs, intrathecal chemotherapy (CHT), and radiotherapy (RT) in primary
      brain lymphomas. METHODS AND MATERIALS: Two hundred eighty-eight immunocompetent
      patients with histologically documented, previously untreated primary brain
      lymphomas, receiving CHT containing high-dose MTX (> or =1 g/m(2)) with or
      without RT were selected from 19 prospective series. The impact on survival of
      the MTX dose (<3 g/m(2) vs.> or =3 g/m(2)), the main drugs, intrathecal CHT, and
      combination CHT (mono-CHT vs. poly-CHT) was assessed, according to the intention
      to-treat principle. The role of post-CHT irradiation (immediate vs. delayed RT)
      was evaluated in 119 patients with a complete response to CHT. The whole brain
      and tumor bed dose (<40 Gy vs. > or =40 Gy) was assessed in 70 irradiated
      complete responders. RESULTS: No difference in overall survival (OS) was detected
      between mono-CHT and combination CHT (p = 0.38). MTX > or =3 g/m(2) (p = 0.04),
      thiotepa (p = 0.03), and intrathecal CHT (p = 0.03) improved the OS, and
      nitrosoureas (p = 0.01) correlated with a worse survival. In multivariate
      analysis, limited to patients receiving MTX > or =3 g/m(2), only the addition of
      cytarabine improved the OS; nitrosoureas reduced MTX efficacy. Of the 119
      complete responders, 70 received immediate RT. A RT dose of > or =40 Gy to the
      whole brain or tumor bed did not improve OS. The 3-year OS was similar between
      the immediate and delayed RT groups. In multivariate analysis, RT delay had no
      negative impact on survival. CONCLUSIONS: MTX > or =3 g/m(2) seems to improve
      survival in primary brain lymphoma patients. The efficacy of additional drugs,
      except for cytarabine, remains unproved. Randomized trials are needed to confirm
      that RT withdrawal yields no detrimental effect in complete responders.

PMID- 11567817
TI  - Radiosurgery for patients with brain metastases: a multi-institutional analysis,
      stratified by the RTOG recursive partitioning analysis method.
AB  - PURPOSE: To estimate the potential improvement in survival for patients with
      brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG)
      recursive partitioning analysis (RPA) class and treated with radiosurgery (RS)
      plus whole brain radiotherapy (WBRT). METHODS AND MATERIALS: An analysis of the
      RS databases of 10 institutions identified patients with brain metastates treated
      with RS and WBRT. Patients were stratified into 1 of 3 RPA classes. Survival was
      evaluated using Kaplan-Meier estimates and proportional hazard regression
      analysis. A comparison of survival by class was carried out with the RTOG results
      in similar patients receiving WBRT alone. RESULTS: Five hundred two patients were
      eligible (261 men and 241 women, median age 59 years, range 26-83). The overall
      median survival was 10.7 months. A higher Karnofsky performance status (p =
      0.0001), a controlled primary (median survival = 11.6 vs. 8.8 months, p =
      0.0023), absence of extracranial metastases (median survival 13.4 vs. 9.1 months,
      p = 0.0001), and lower RPA class (median survival 16.1 months for class I vs.
      10.3 months for class II vs. 8.7 months for class III, p = 0.000007) predicted
      for improved survival. Gender, age, primary site, radiosurgery technique, and
      institution were not prognostic. The addition of RS boosted results in median
      survival (16.1, 10.3, and 8.7 months for classes I, II, and III, respectively)
      compared with the median survival (7.1, 4.2, and 2.3 months, p <0.05) observed in
      the RTOG RPA analysis for patients treated with WBRT alone. CONCLUSION: In the
      absence of randomized data, these results suggest that RS may improve survival in
      patients with BM. The improvement in survival does not appear to be restricted by
      class for well-selected patients.

PMID- 11567818
TI  - Cost analysis of erythropoietin versus blood transfusions for cervical cancer
      patients receiving chemoradiotherapy.
AB  - PURPOSE: Red blood cell (RBC) transfusions or erythropoietin (EPO) can be used to
      evade the detrimental effects of anemia during radiotherapy, but the economic
      consequences of selecting either intervention are not well defined. The RBC
      transfusion needs during chemoradiotherapy for cervix cancer were quantified to
      allow comparison of RBC transfusion costs with the projected cost of EPO in this
      setting. METHODS AND MATERIALS: For patients receiving pelvic radiotherapy,
      weekly cisplatin, and brachytherapy, the RBC units transfused during treatment
      were tallied. RBC transfusion costs per unit included the blood itself,
      laboratory fees, and expected value (risk multiplied by cost) of transfusion
      related viral illness. EPO costs included the drug itself and supplemental RBC
      transfusions when hemoglobin was not adequately maintained. An EPO dosage based
      on reported usage in cervix cancer patients was applied. RESULTS: Transfusions
      were given for hemoglobin <10 g/dL. Among 12 consecutive patients, 10 needed at
      least 1 U of RBC before or during treatment, most commonly after the fifth week.
      A total of 37 U was given during treatment, for an average of 3.1 U/patient. The
      sum total of the projected average transfusion-related costs was $990, compared
      with the total projected EPO-related costs of $3869. CONCLUSIONS: Because no
      proven clinical advantage has been documented for EPO compared with RBC
      transfusions to maintain hemoglobin during cervix cancer treatment, for most
      patients, transfusions are an appropriate and appealingly less expensive option.

PMID- 11567819
TI  - Isolated paraaortic lymph node recurrence after definitive irradiation for
      cervical carcinoma.
AB  - PURPOSE: To evaluate the clinical features of isolated paraaortic lymph node
      (PALN) recurrence after definitive radiotherapy, and analyze the prognostic
      factors and effect of salvage treatment. METHODS AND MATERIALS: Of a total 876
      patients who received pelvic radiotherapy after the diagnosis of primary cervical
      carcinoma, 26 were found to have isolated PALN recurrence as the first recurrent
      site, and these patients enrolled in this study. Only those with primary-site
      carcinoma controlled and who were free of other distant metastases were eligible.
      Nineteen of the 26 patients accepted salvage therapy. Fourteen patients accepted
      concurrent chemoradiation (CCRT), 1 accepted radiation to the paraaortic region,
      and 4 accepted chemotherapy alone. Clinical parameters evaluated included tumor
      markers (SCC and CEA) and image studies. RESULTS: Seven of the 26 patients were
      alive and disease-free. All 7 survivors had salvage treatment with radiation to
      the paraaortic region and concurrent cisplatin-based chemotherapy. None of the
      patients receiving chemotherapy or radiation alone enjoyed long-term, disease
      free survival. The 5-year survival rate for isolated PALN recurrence of the 14
      patients who accepted salvage concurrent chemoradiation (CCRT) was 51.2%. The
      presence of a clinical symptom at the time of PALN recurrence was analyzed. Seven
      of the 12 asymptomatic patients and none of the 14 symptomatic patients survived
      without disease after salvage treatment. The SCC levels at recurrence showed a
      statistically significant relationship to disease-free survival. CONCLUSIONS: An
      SCC level of < or = 4 ng/ml and a lack of symptoms at the time of recurrence were
      good prognostic factors in isolated PALN recurrence after primary radiation
      therapy. In addition to concurrent CCRT, periodical surveillance with tumor
      markers and imaging studies allowed early detection and salvage of those
      patients.

PMID- 11567820
TI  - Does increased nerve length within the treatment volume improve trigeminal
      neuralgia radiosurgery? A prospective double-blind, randomized study.
AB  - PURPOSE: To test the hypothesis that increasing the nerve length within the
      treatment volume for trigeminal neuralgia radiosurgery would improve pain relief.
      METHODS AND MATERIALS: Eighty-seven patients with typical trigeminal neuralgia
      were randomized to undergo retrogasserian gamma knife radiosurgery (75 Gy maximal
      dose with 4-mm diameter collimators) using either one (n = 44) or two (n = 43)
      isocenters. The median follow-up was 26 months (range 1-36). RESULTS: Pain relief
      was complete in 57 patients (45 without medication and 12 with low-dose
      medication), partial in 15, and minimal in another 15 patients. The actuarial
      rate of obtaining complete pain relief (with or without medication) was 67.7% +/-
      5.1%. The pain relief was identical for one- and two-isocenter radiosurgery. Pain
      relapsed in 30 of 72 responding patients. Facial numbness and mild and severe
      paresthesias developed in 8, 5, and 1 two-isocenter patients vs. 3, 4, and 0 one
      isocenter patients, respectively (p = 0.23). Improved pain relief correlated with
      younger age (p = 0.025) and fewer prior procedures (p = 0.039) and complications
      (numbness or paresthesias) correlated with the nerve length irradiated (p =
      0.018). CONCLUSIONS: Increasing the treatment volume to include a longer nerve
      length for trigeminal neuralgia radiosurgery does not significantly improve pain
      relief but may increase complications.

PMID- 11567821
TI  - Acute and late radiotherapy toxicity in patients with inflammatory bowel disease.
AB  - PURPOSE: To evaluate the incidence of gastrointestinal complications in patients
      with inflammatory bowel disease (IBD) receiving radiotherapy (RT) and to identify
      possibly avoidable factors associated with these complications. METHODS AND
      MATERIALS: Twenty-four patients were identified and their records reviewed; all
      had a history of IBD before receiving RT to fields encompassing some portion of
      the gastrointestinal tract (Crohn's disease) or to the abdomen or pelvis
      (ulcerative colitis or IBD not otherwise specified). RESULTS: Five of 24 patients
      (21%) experienced Grade > or =3 acute gastrointestinal toxicity; all 5 received
      concurrent chemotherapy. Two of 24 patients (8%) experienced Grade > or =3 late
      gastrointestinal toxicity. There were no significant correlations between
      complications and IBD type, prior IBD-related surgery, use of medications for
      IBD, or status of IBD. CONCLUSION: Patients with IBD may have an increased risk
      for severe acute RT-related gastrointestinal complications that is more modest
      than generally perceived, because all patients who had Grade > or =3 acute
      complications in this study had received concurrent chemotherapy (p = 0.04).
      Further study is needed to assess this risk, as well as the impact of RT on these
      patients' future gastrointestinal morbidity.

PMID- 11567822
TI  - Dislocation of small bowel volume within box pelvic treatment fields, using new
      "up down table" device.
AB  - PURPOSE: To present the impact of a novel minimization device, the up down table
      (UDT), on the volume of small bowel included within a 4-field pelvic irradiation
      plan. METHODS: A polystyrene bowel displacement standard mold was created and
      added to a customized vacuum cushion (Vac Lok) formed around the abdomen and legs
      of each patient in the prone position. Two hundred seventy-seven consecutive
      patients with pelvic malignancies treated with the UDT device were compared with
      1 historic series (68 cases) treated at our division. Small bowel contrast dyes
      at the time of simulation were used in all patients. RESULTS: The average volume
      of small bowel within the planning target volume (high-dose volume, calculated
      with Gallagher method) was 100 cm(3) (median 49 +/- 114) in the series treated
      with standard box technique and 23 cm(3) (median 0 +/- 64) in the series treated
      with the UDT (p < 0.001). The average volume of small bowel included in any
      isodose (any-dose volume) was 505 cm(3) (median 447 +/- 338) and 158 cm(3)
      (median 69 +/- 207), respectively (p < 0.001). The incidence of G1, G2, and G3
      acute enteric toxicity (Radiation Therapy Oncology Group criteria) in the UDT
      series was 16%, 15%, and 1.5%; in the standard box technique, it was 28%, 25%,
      and 3%, respectively (p < 0.05). The incidence of acute enteric toxicity directly
      correlated with the irradiated small bowel volume. In the UDT series, the 5-year
      actuarial incidence of G3 chronic enteric toxicity was 1.8%. The setup
      procedures, analyzed in 18 cases, revealed no systematic errors and a standard
      deviation equal to +/-5 mm for random errors. CONCLUSIONS: The UDT technique is
      comfortable, inexpensive, highly reproducible, and permits an almost full bowel
      displacement from standard radiotherapy fields.

PMID- 11567823
TI  - C225 antiepidermal growth factor receptor antibody enhances tumor
      radiocurability.
AB  - PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) has been
      correlated with tumor resistance to radiation. Blockade of EGFR with C225 anti
      EGFR antibody was previously shown to synergistically enhance radiation-induced
      tumor growth delay. The purpose of this study was to assess whether C225 can
      increase tumor cure by radiation. METHODS AND MATERIALS: Nude mice bearing 8-mm
      diameter A431 tumor xenografts in the hind leg were treated with C225 antibody,
      graded single doses of local tumor irradiation, or both. C225 was given i.p. at a
      dose of 1 mg/mouse 6 h before irradiation or 6 h before and 3 plus 6 days after
      irradiation. Tumor cure was the treatment endpoint assessed by the TCD(50) assay
      120 days after treatment. The onset of recurrences of tumors not cured was also
      determined. RESULTS: C225 antibody increased the antitumor effects of radiation
      by reducing TCD(50) values and delaying tumor recurrences. Tumor radiocurability
      was enhanced by a factor of 1.18 by a single dose and by a factor of 1.92 by
      three doses of C225. Likewise, the appearance of tumor recurrences was delayed by
      a factor of 1.37 by a single dose and by a factor of 2.13 by three doses of C225.
      CONCLUSION: The data presented here demonstrate that C225 can increase tumor
      radiocurability and delay the appearance of recurrences of tumors not cured by
      radiation treatment.

PMID- 11567824
TI  - Tumor angiogenesis of low-grade astrocytomas measured by dynamic susceptibility
      contrast-enhanced MRI (DSC-MRI) is predictive of local tumor control after
      radiation therapy.
AB  - PURPOSE: To assess regional cerebral blood volume (rCBV) as a surrogate marker of
      angiogenesis in patients with low-grade fibrillary astrocytoma before radiation
      therapy and to correlate measured values with clinical outcome after fractionated
      stereotactic radiotherapy (FSRT). METHODS: Twenty-five patients with
      histologically proven fibrillary astrocytomas were examined using dynamic
      susceptibility contrast-enhanced MRI before radiotherapy. Radiotherapy was
      delivered to mean and median total doses of 60.9 and 60 Gy, respectively (range
      55.8-66 Gy). During MRI for treatment planning, 55 T2*-weighted gradient echo
      images were acquired before, during, and after i.v. contrast-bolus injection. The
      acquired signal-time curves were converted into concentration-time curves. By
      normalization to an arterial input function, absolute and relative rCBV values
      were calculated. Measured pretherapeutic rCBV data were correlated to outcome in
      terms of local control after FSRT. RESULTS: Mean pretherapeutic rCBV for
      astrocytomas was 6.5 +/- 3.7 ml/100 g tissue. Mean and median follow-up times
      were 47.8 and 52 months, respectively. Fifteen tumors recurred during the period,
      with a mean and median latency of 39.1 and 42 months, respectively. Tumors
      recurring earlier than 42 months after FSRT showed a higher pretreatment rCBV
      than tumors recurring later and tumors in continued local control (8.12 +/- 4.48
      ml/100 g vs. 6.0 +/- 2.3 ml/100 g and 4.73 +/- 2.47 ml/100 g; p = 0.02 and p =
      0.03). The respective ratios of tumor rCBV in early recurrent tumors to gray
      matter and white matter rCBV were 0.98 +/- 0.38 and 2.17 +/- 1.36 as compared
      with 0.79 +/- 0.14 and 1.44 +/- 0.29 in locally controlled tumors (p = 0.074 and
      p = 0.056). CONCLUSIONS: In fibrillary low-grade astrocytomas, a noninvasive
      assessment of angiogenesis as indicated by rCBV measurement was feasible. The
      present data suggest that high pretherapeutic angiogenic activity in low-grade
      astrocytomas indicates a subgroup of tumors at higher risk for early local
      recurrence or malignant transformation after FSRT.

PMID- 11567825
TI  - Repopulation of FaDu human squamous cell carcinoma during fractionated
      radiotherapy correlates with reoxygenation.
AB  - PURPOSE: FaDu human squamous cell carcinoma (FaDu-hSCC) showed a clear-cut time
      factor during fractionated radiotherapy (RT) under ambient blood flow. It
      remained unclear whether this is caused solely by proliferation or if
      radioresistance resulting from increasing hypoxia contributed to this phenomenon.
      To address this question, repopulation of clonogenic FaDu cells during
      fractionated RT under clamp hypoxia was determined by local tumor control assays,
      and compared to the results after irradiation with the same regimen under ambient
      blood flow. METHODS AND MATERIALS: FaDu-hSCC was transplanted into the right hind
      leg of NMRI nu/nu mice. In the first set of experiments, irradiation was
      performed under clamp hypoxia. After increasing numbers of 3 Gy fractions (time
      intervals 24 h or 48 h), graded top-up doses were given to determine the TCD(50)
      (dose required to control 50% of the tumors). In the second set of experiments,
      all 3 Gy fractions were applied under ambient conditions, but as in the previous
      experiments the graded top-up doses were given under clamp hypoxia. A total of 26
      TCD(50) assays were performed and analyzed using maximum likelihood techniques.
      RESULTS: With increasing numbers of daily fractions, the top-up TCD(50) under
      clamp hypoxia decreased from 39.4 Gy [95% CI 36, 42] after single dose to 19.8 Gy
      [15, 24] after 18 fractions in 18 days and to 37.8 Gy [31, 44] after 18 fractions
      in 36 days. The results were consistent with biphasic repopulation, with a switch
      to rapid repopulation after about 22 days [13, 30]. The clonogen doubling time
      (T(clon)) decreased from 9.8 days [0, 21] in the beginning of RT to 3.4 days
      after 22 days. Under ambient blood flow the top-up TCD(50) decreased from 37.6 Gy
      [34, 40] after single dose irradiation to 0 Gy [0, 1] after 18 fractions in 18
      days and 22.4 Gy [18, 27] after 18 fractions in 36 days. Similar to results from
      irradiations under clamp hypoxia, the ambient data were consistent with a
      biphasic course of clonogen inactivation. Comparison of both data sets revealed
      significant reoxygenation after 12 fractions. CONCLUSIONS: Our data are most
      consistent with a biphasic course of clonogen repopulation during fractionated RT
      of FaDu-hSCC under clamp hypoxia with a switch in T(clon) after about 22 days of
      treatment ("dog-leg"). A similar biphasic course of cell repopulation was
      observed under ambient conditions. The temporal coincidence between repopulation
      and reoxygenation suggests that the latter might be the stimulus for
      proliferation in FaDu tumors.

PMID- 11567826
TI  - Simultaneous administration of glucose and hyperoxic gas achieves greater
      improvement in tumor oxygenation than hyperoxic gas alone.
AB  - PURPOSE: To test the feasibility of hyperglycemic reduction of oxygen consumption
      combined with oxygen breathing (O(2)), to improve tumor oxygenation. METHODS AND
      MATERIALS: Fischer-344 rats bearing 1 cm R3230Ac flank tumors were anesthetized
      with Nembutal. Mean arterial pressure, heart rate, tumor blood flow ([TBF], laser
      Doppler flowmetry), pH, and pO(2) were measured before, during, and after glucose
      (1 or 4 g/kg) and/or O(2). RESULTS: Mean arterial pressure and heart rate were
      unaffected by treatment. Glucose at 1 g/kg yielded maximum blood glucose of 400
      mg/dL, no change in TBF, reduced tumor pH (0.17 unit), and 3 mm Hg pO(2) rise.
      Glucose at 4 g/kg yielded maximum blood glucose of 900 mg/dL, pH drop of 0.6
      unit, no pO(2) change, and reduced TBF (31%). Oxygen tension increased by 5 mm Hg
      with O(2). Glucose (1 g/Kg) + O(2) yielded the largest change in pO(2) (27 mm
      Hg); this is highly significant relative to baseline or either treatment alone.
      The effect was positively correlated with baseline pO(2), but 6 of 7 experiments
      with baseline pO(2) < 10 mm Hg rose above 10 mm Hg after combined treatment.
      CONCLUSION: We demonstrated the feasibility of combining hyperglycemia with O(2)
      to improve tumor oxygenation. However, some cell lines are not susceptible to the
      Crabtree effect, and the magnitude is dependent on baseline pO(2). Additional or
      alternative manipulations may be necessary to achieve more uniform improvement in
      pO(2).

PMID- 11567827
TI  - Inhibition of epidural scar tissue formation after spinal surgery: external
      irradiation vs. spinal membrane application.
AB  - PURPOSE: The scar tissue that forms after lumbar dissection is a severe
      complication and a cause of lumbar and radicular pain. It was recently shown that
      radiotherapy could inhibit peridural fibrosis after laminectomy. In this study,
      the efficiency of external irradiation was compared with spinal membrane
      application. METHOD AND MATERIALS: Thirty male New Zealand rabbits underwent L5
      laminectomy. Ten rabbits each received a single fraction of 900-cGy external
      irradiation administered by 9-MeV electron beam 24 h after the surgery. Ten other
      rabbits each had spinal membrane applied during laminectomy. The remaining 10
      rabbits constituted the control group. All of the rabbits were killed 30 days
      after the laminectomy. Axial histologic sections through the laminectomy defect
      were evaluated. Each specimen was scored for the extent and density of fibrosis
      and arachnoidal adherence. RESULTS: The extent and density of fibrosis and
      arachnoidal adherence differed significantly between the control group and the
      treatment groups (p < 0.05). However, the extent and density of fibrosis and
      arachnoidal adherence did not differ significantly between the spinal membrane
      and irradiation groups (p > 0.05). CONCLUSION: This preliminary study showed that
      high-single-fraction/low-total-dose administered postoperatively can successfully
      inhibit postsurgical epidural fibrosis as effectively as applied spinal membrane.

PMID- 11567828
TI  - Dosimetric comparison of radionuclides for therapy of somatostatin receptor
      expressing tumors.
AB  - PURPOSE: Therapy of tumors expressing somatostatin receptors, sstr, has recently
      been clinically tested using somatostatin analogues labeled with (111)In and
      (90)Y. Several other radionuclides, i.e., (131)I, (161)Tb, (64)Cu, (188)Re,
      (177)Lu, and (67)Ga, have also been proposed for this type of therapy. The aim of
      this work was to investigate the usefulness of the above-mentioned radionuclides
      bound to somatostatin analogues for tumor therapy. METHODS: Biokinetic data of
      (111)In-labeled octreotide in mice and man were used, primarily from our studies
      but sometimes from the literature. Dosimetric calculations were performed with
      the assumption that biokinetics were similar for all radionuclides bound to
      somatostatin analogues. The cumulated tumor:normal-tissue activity concentration,
      TNC was calculated for the various physical half-lives of the radionuclides.
      Using mathematical models, the tumor:normal-tissue mean absorbed dose rate ratio,
      TN D and tumor:normal-tissue mean absorbed dose ratio, TND, were calculated for
      various tumor sizes in mice and humans. RESULTS: TNC of radionuclide-labeled
      octreotide increased with physical half-life for most organs, both in mice and in
      humans. TN D showed that radionuclides emitting electrons with too high energy
      are not suitable for therapy of small tumors. Furthermore, radionuclides with a
      higher frequency of photon emissions relative to electron emissions will yield
      lower TN D and are thus less suitable for therapy than radionuclides with a lower
      frequency of photon emissions. The TND was highest for (161)Tb in both mice and
      humans. CONCLUSIONS: The results demonstrate that long-lived radionuclides, which
      emit electrons with rather low energy and which have low frequency of photon
      emissions, should be the preferred therapy for disseminated small sstr-expressing
      tumors.

PMID- 11567829
TI  - The novel taxane analogs, BMS-184476 and BMS-188797, potentiate the effects of
      radiation therapy in vitro and in vivo against human lung cancer cells.
AB  - PURPOSE: To evaluate the novel taxane analogs, BMS-184476 and BMS-188797, as
      potential radiosensitizers in vitro and in vivo. METHODS AND MATERIALS: Human
      H460 lung cancer cells were incubated with either paclitaxel or a taxane analog
      and irradiated at various times. Surviving fractions were then determined using a
      clonogenic assay. Three different schedules were used: (A) 1-h drug incubation
      with radiation at t = 8 h, (B) 1-h drug incubation with radiation at t = 24 h,
      (C) 24-h drug incubation with radiation immediately after. Cell cycle
      redistribution by taxanes alone was measured with propidium iodide and flow
      cytometry. Percent apoptosis was also measured using 7-aminoactinomycin D (7-AAD)
      staining with flow cytometry. For in vivo studies, H460 cell xenografts were used
      in nude mice. Tumors were grown s.c. on the flank and then treated with BMS
      184476 (10 mg/kg i.p. injection, Days 0, 2, and 4) and/or radiation (2 Gy/day,
      Days 0-4). Tumor growth delay was then measured for each treatment group.
      RESULTS: The mean in vitro radiation dose enhancement ratios of BMS-184476, BMS
      188797, and paclitaxel were 1.76, 1.49, and 1.31 for Schedules A, B, and C,
      respectively. Isobologram analysis showed that BMS-184476 was synergistic with
      radiation using Schedule A. Treatment with taxanes caused an increase in the
      percentage of G2/M cells at the time of irradiation. The mean fold increases in
      the %G2/M above control values for all three drugs were 5.6, 2.5, and 1.7 for
      Schedules A, B, and C, respectively. The combined effects of taxanes plus
      radiation on the induction of apoptosis were additive for all three drugs. In
      vivo studies showed that BMS-184476 can enhance the effects of fractionated
      radiotherapy, with an average enhancement factor of 1.66 obtained from three
      independent experiments. CONCLUSIONS: These results demonstrated that the novel
      taxane analogs, BMS-184476 and BMS-188797, can enhance the effects of radiation
      in human lung cancer cells both in vitro and in vivo. These data also support the
      hypothesis that a G2/M block is involved in the radiosensitization caused by the
      taxanes.

PMID- 11567830
TI  - Vinblastine and hyperthermia target the neovasculature in BT(4)AN rat gliomas:
      therapeutic implications of the vascular phenotype.
AB  - PURPOSE: The antivascular and antitumor activity of vinblastine and hyperthermia
      at different tumor volumes were examined in the subcutaneous (s.c.) BT(4)An rat
      glioma model. METHODS AND MATERIALS: The influence of vinblastine (3 mg/kg) and
      hyperthermia (44 degrees C/60 min) on tumor growth was assessed in small (100
      mm(3)) and large (200 mm(3)) BT(4)An tumors. To disclose how vinblastine and
      hyperthermia interacted in the neoplasms, tumor blood flow and the extent of
      vascular damage, hypoxia, cell proliferation, and apoptosis were assessed after
      treatment. The content of smooth muscle cells/pericytes in the tumor vasculature
      was examined in small and large tumors to assess how the vascular phenotype
      changed during tumor growth. RESULTS: In the large tumors, vinblastine reduced
      the blood flow, but the tumor growth was not affected. The combination of drug
      and local heating yielded massive vascular damage and a significant tumor
      response. The small neoplasms had a higher content of smooth muscle
      cells/pericytes in the vessel walls (host vasculature), and the tumor vasculature
      displayed a higher resistance to vascular damage than the large neoplasms. Yet,
      vinblastine alone exhibited a potent antiproliferative activity and induced
      massive apoptosis in the small tumors, and the drug significantly inhibited tumor
      growth. The addition of hyperthermia yielded no additional growth delay in the
      small tumors. CONCLUSION: The antivascular properties of vinblastine and
      hyperthermia can be exploited to facilitate vascular damage in BT(4)An solid
      tumors with a low content of host vasculature.

PMID- 11567831
TI  - Multi-isocenter stereotactic radiotherapy: implications for target dose
      distributions of systematic and random localization errors.
AB  - PURPOSE: This investigation examined the effect of alignment and localization
      errors on dose distributions in stereotactic radiotherapy (SRT) with arced
      circular fields. In particular, it was desired to determine the effect of
      systematic and random localization errors on multi-isocenter treatments. METHODS
      AND MATERIALS: A research version of the FastPlan system from Surgical Navigation
      Technologies was used to generate a series of SRT plans of varying complexity.
      These plans were used to examine the influence of random setup errors by
      recalculating dose distributions with successive setup errors convolved into the
      off-axis ratio data tables used in the dose calculation. The influence of
      systematic errors was investigated by displacing isocenters from their planned
      positions. RESULTS: For single-isocenter plans, it is found that the influences
      of setup error are strongly dependent on the size of the target volume, with
      minimum doses decreasing most significantly with increasing random and systematic
      alignment error. For multi-isocenter plans, similar variations in target dose are
      encountered, with this result benefiting from the conventional method of
      prescribing to a lower isodose value for multi-isocenter treatments relative to
      single-isocenter treatments. CONCLUSIONS: It is recommended that the systematic
      errors associated with target localization in SRT be tracked via a thorough
      quality assurance program, and that random setup errors be minimized by use of a
      sufficiently robust relocation system. These errors should also be accounted for
      by incorporating corrections into the treatment planning algorithm or,
      alternatively, by inclusion of sufficient margins in target definition.

PMID- 11567832
TI  - The TALON removable head frame system for stereotactic radiosurgery/radiotherapy:
      measurement of the repositioning accuracy.
AB  - PURPOSE: To present the TALON removable head frame system as an immobilization
      device for single-fraction intensity-modulated stereotactic radiosurgery (IMRS)
      and fractionated stereotactic intensity-modulated radiotherapy (FS-IMRT); and to
      evaluate the repositioning accuracy by measurement of anatomic landmark
      coordinates in repeated computed tomography (CT) examinations. METHODS AND
      MATERIALS: Nine patients treated by fractionated stereotactic intensity-modulated
      radiotherapy underwent repeated CTs during their treatment courses. We evaluated
      anatomic landmark coordinates in a total of 26 repeat CT data sets and respective
      x, y, and z shifts relative to their positions in the nine treatment-planning
      reference CTs. An iterative optimization algorithm was employed using a root mean
      square scoring function to determine the best-fit orientation of subsequent sets
      of anatomic landmark measurements relative to the original image set. This
      allowed for the calculation of the x, y, and z components of translation of the
      target isocenter for each repeat CT. In addition to absolute target isocenter
      translation, the magnitude (sum vector) of isocenter motion and the
      patient/target rotation about the three principal axes were calculated. RESULTS:
      Anatomic landmark analysis over a treatment course of 6 weeks revealed a mean
      target isocenter translation of 0.95 +/- 0.55, 0.58 +/- 0.46, and 0.51 +/- 0.38
      mm in x, y, and z directions, respectively. The mean magnitude of isocenter
      translation was 1.38 +/- 0.48 mm. The 95% confidence interval ([CI], mean
      translation plus two standard deviations) for repeated isocenter setup accuracy
      over the 6-week period was 2.34 mm. Average rotations about the x, y, and z axes
      were 0.41 +/- 0.36, 0.29 +/- 0.25, and 0.18 +/- 0.15 degrees, respectively.
      Analysis of the accuracy of the first repeated setup control, representative of
      single-fraction stereotactic radiosurgery situations, resulted in a mean target
      isocenter translation in the x, y, and z directions of 0.52 +/- 0.38, 0.56 +/-
      0.30, and 0.46 +/- 0.25 mm, respectively. The mean magnitude of isocenter
      translation was 0.99 +/- 0.28 mm. The 95% confidence interval for these
      radiosurgery situations was 1.55 mm. Average rotations at first repeated setup
      control about the x, y, and z axes were 0.24 +/- 0.19, 0.19 +/- 0.17, and 0.19 +/
      0.12 degrees, respectively. CONCLUSION: The TALON relocatable head frame was
      seen to be well suited for immobilization and repositioning of single-fraction
      stereotactic radiosurgery treatments. Because of its unique removable design, the
      system was also seen to provide excellent repeat immobilization and alignment for
      fractionated stereotactic applications. The exceptional accuracy for the single
      fraction stereotactic radiosurgical application of the system was seen to
      deteriorate only slightly over a 6-week fractionated stereotactic treatment
      course.

PMID- 11567834
TI  - Adoption of the AHCPR Clinical Practice Guideline for Smoking Cessation: a survey
      of California's HMOs.
AB  - OBJECTIVE: Our objective was to assess the degree to which health maintenance
      organizations (HMOs) and Medicaid managed care (MMC) plans in California have
      adopted the 1996 AHCPR Clinical Practice Guideline for Smoking Cessation. (AHCPR
      [U.S. Agency for Health Care Policy and Research] was renamed AHRQ [Agency for
      Healthcare Research and Quality] in 1999.) METHODS: A fax survey of 13 licensed
      HMOs and 21 MMC plans operating in California in 1999 with up to 10 follow-up
      contacts by telephone, mail, fax, and/or electronic mail. RESULTS: Awareness of
      the AHCPR guideline is widespread, and all HMOs in California in 1999 offered
      coverage for at least one treatment for smoking cessation. We found that 77% of
      the HMOs in California were aware of the AHCPR guideline, but less than half had
      used it to design benefits or distribute treatment guidelines to medical care
      providers in their networks. While only 23% of California HMOs covered the
      nicotine patch or gum, 69% covered at least one form of the pharmacotherapy and
      one type of counseling to treat tobacco dependence. In addition, a majority of
      the HMOs and MMC plans inform their members about coverage for smoking cessation
      treatments and inform providers about their role in helping smokers to quit.
      CONCLUSION: Considerable progress has been made in increasing access to effective
      smoking cessation treatments in California's managed care organizations over the
      last 10 years. Future efforts and research must concentrate on: (1) adopting the
      2000 Public Health Service Clinical Practice Guideline on Treating Tobacco Use
      and Dependence, (2) increasing purchaser demand for coverage of tobacco
      dependence treatments, (3) increasing health plan documentation and monitoring of
      member smoking status, and (4) increasing provider provision of effective tobacco
      dependence treatments.

PMID- 11567835
TI  - Adolescent smoking in Wuhan, China: baseline data from the Wuhan Smoking
      Prevention Trial.
AB  - BACKGROUND: This study reports the prevalence of adolescent smoking in the urban
      and rural areas of Wuhan, China, the capital of Hubei Province, on the Yangtze
      River in central China. METHODS: Smoking behavior was examined by age, gender,
      and urbanicity as part of the Wuhan Smoking Prevention Trial. Subjects included
      6994 seventh- to ninth-grade students attending 22 randomly selected schools in
      urban and rural districts. Outcome measures included lifetime smoking, past-30
      day smoking, established smoking (>100 cigarettes in lifetime), and
      susceptibility to smoking (absence of a firm commitment not to smoke). RESULTS:
      Lifetime smoking prevalence was 47% among boys and 18% among girls. Past-30-day
      smoking prevalence was 16% among boys and 4% among girls. Established smoking
      prevalence was 2% among boys and 0% among girls. The prevalence of susceptibility
      to smoking was 31% among boys and 10% among girls. Smoking increased
      significantly with age (p<.0005). Susceptibility was more prevalent in rural
      areas than in urban areas (p<.05), but there were no urban-rural differences in
      lifetime, past 30-day smoking, or established smoking. Trend analyses revealed
      that smoking increased with age more rapidly among boys than among girls (p<.05).
      Smoking was more prevalent among rural boys than among urban boys, but it was
      more prevalent among urban girls than among rural girls (p<.05). CONCLUSIONS:
      Adolescent smoking is a significant public health problem in China. Boys are at
      particularly high risk, as are girls living in urban areas. Effective smoking
      prevention programs for adolescents, as well as restrictions on tobacco industry
      marketing and youth access to tobacco, are needed to prevent tobacco-related
      morbidity and mortality in China.

PMID- 11567836
TI  - Beyond screening for domestic violence: a systems model approach in a managed
      care setting.
AB  - BACKGROUND: Implementation of screening guidelines for domestic violence has been
      challenging. The multifaceted "systems model" may provide an effective means to
      improve domestic violence screening, identification, and intervention in the
      healthcare setting. METHODS: We developed: (1) a systems model approach using
      tools for effective referral, evaluation, and reporting of domestic violence; (2)
      materials for distribution to female patients; (3) training for social service
      and mental health clinicians to provide domestic violence evaluation; and (4)
      strong links to the community. SETTING: A nonprofit, managed care facility in
      Richmond, California. PARTICIPANTS: Staff and members of the managed care plan.
      MAIN OUTCOME MEASURES: (1) Increased screening for domestic violence by
      clinicians; (2) increased awareness of the healthcare facility as a resource for
      domestic violence assistance; and (3) increased member satisfaction with the
      health plan's efforts to address domestic violence. RESULTS: The number of
      clinician referrals and patient self-referrals to an on-site domestic violence
      evaluator increased more than twofold. A pre-intervention and post-intervention
      phone survey of members seen for routine checkup showed an increase in member
      recall of being asked about domestic violence. After intervention, statistically
      significant increases were seen in members' perception that the health plan was
      concerned about the health effects of domestic violence (p<0.0001) and about
      members' satisfaction with the health plan's efforts to address this issue
      (p<0.0001). CONCLUSIONS: A systems model approach improved domestic violence
      services in a managed care health setting within 1 year and affected clinicians'
      behavior as well as health plan members' experience. This successful
      implementation makes it possible to address critical research questions about the
      impact of a healthcare intervention for victims of domestic violence in a managed
      healthcare setting.

PMID- 11567837
TI  - The delivery of preventive services for patient symptoms.
AB  - BACKGROUND: Although data are available on rates of delivery of preventive
      services by primary care physicians, the proportion of services delivered because
      of related symptoms or signs, rather than for primary or secondary prevention of
      disease is not known. METHODS: Research nurses directly observed 4454 consecutive
      visits to 138 practicing family physicians. Direct observation was used to
      identify delivery of 36 different services recommended by the U.S. Preventive
      Services Task Force and to assess whether delivery of these services was
      associated with related signs or symptoms. RESULTS: One or more preventive
      services were delivered in 33% of visits, with rates ranging from 0.2% (HIV
      prevention) to 19.9% (tobacco counseling). In contrast to pure prevention,
      services were frequently performed for assessment or care of symptoms or signs,
      with the ratio ranging from 0% (eye examination; car seat, poison control, and
      HIV prevention counseling) to 66.7% (hearing test). Physicians varied
      considerably in the frequency at which their delivery of recommended preventive
      services was associated with patient symptoms, from 0% to 100% for screening
      services and from 0% to 100% for counseling services. CONCLUSIONS: Because of the
      illness focus of most primary care visits, preventive service delivery is often
      associated with related signs or symptoms. Care of illnesses appears to present
      an important impetus and perhaps teachable moments for providing preventive care.
      Clinician variability in preventive service delivery for patient symptoms shows
      an opportunity to improve the primary and secondary prevention focus of practice
      to meet public health prevention goals.

PMID- 11567838
TI  - Are rural residents less likely to obtain recommended preventive healthcare
      services?
AB  - BACKGROUND: This study examined rural-urban differences in utilization of
      preventive healthcare services and assessed the impact of rural residence,
      demographic factors, health insurance status, and health system characteristics
      on the likelihood of obtaining each service. METHODS: National data from the 1997
      Behavioral Risk Factor Surveillance System (BRFSS) and the 1999 Area Resource
      File were used to evaluate the adequacy of preventive services obtained by rural
      and urban women and men, using three sets of nationally accepted preventive
      services guidelines from the American Cancer Society, U.S. Preventive Services
      Task Force, and Healthy People 2010. Logistic regression models were developed to
      control for the effect of demographic factors, health insurance status, and
      health system characteristics. RESULTS: Rural residents are less likely than
      urban residents to obtain certain preventive health services and are further
      behind urban residents in meeting Healthy People 2010 objectives. CONCLUSIONS:
      Efforts to increase rural preventive services utilization need to build on
      federal, state, and community-based initiatives and to recognize the special
      challenges that rural areas present.

PMID- 11567839
TI  - Physician advice and support for physical activity: results from a national
      survey.
AB  - BACKGROUND: It is increasingly well documented that physical activity (PA) is a
      key preventive behavior and that visits to a physician provide an important
      opportunity for advice and counseling. This paper reports on physician counseling
      behaviors regarding PA and other chronic disease risk factors from a national
      survey. METHODS: A diverse sample of U.S. adults (N=1818), with oversampling of
      lower-income households, was surveyed about their PA level as well as a host of
      social, environmental, and physician counseling issues. RESULTS: Overall, 28% of
      respondents reported receiving physician advice to increase their PA level. Of
      those who received advice, only 38% received help formulating a specific activity
      plan and 42% received follow-up support. Patients who received advice and support
      were more likely to be older, nonwhite, and to have more chronic illnesses and
      more contact with their doctor. CONCLUSIONS: Physician advice, counseling, and
      follow-up are important components of the social-environmental supports needed to
      increase population PA levels. Health system changes, including teaching
      communication skills, prompts to use those skills, and system changes to support
      attention to PA, are needed to extend promotion of PA to more patients.

PMID- 11567840
TI  - Use of diabetes preventive care and complications risk in two African-American
      communities.
AB  - BACKGROUND: We examined levels of diabetes preventive care services and glycemic
      and lipid control among African Americans with diabetes in two North Carolina
      communities. METHODS: Cross-sectional, population-based study of 625 African
      American adults with diagnosed diabetes. Participants had a household interview
      to determine receipt of preventive care services including glycosylated
      hemoglobin (HbA(1c)), blood pressure, lipid, foot, dilated eye, and dental
      examinations; diabetes education; and health promotion counseling. A total of 383
      gave blood samples to determine HbA(1c) and lipid values. RESULTS: Annual dilated
      eye, foot, and lipid examinations were reported by 70% to 80% of the population,
      but only 46% reported HbA(1c) tests. Rates of regular physical activity (31%) and
      daily self-monitoring of blood glucose (40%) were low. Sixty percent of the
      population had an HbA(1c) level >8% and one fourth had an HbA(1c) level >10%.
      Half of the population had a low-density lipoprotein value >130 mg/dL. Lack of
      insurance was the most consistent correlate of inadequate care (odds ratio
      [OR]=2.3; 95% confidence interval [CI]=1.3-3.9), having HbA(1c) >9.5% (OR=2.1,
      95% CI=1.1-4.2), and LDL levels >130 mg/dL (OR=2.1; 95% CI=1.0-4.5). CONCLUSIONS:
      Levels of diabetes preventive care services were comparable to U.S. estimates,
      but glycemic and lipid control and levels of self-management behaviors were poor.
      These findings indicate a need to understand barriers to achieving and
      implementing good glycemic and lipid control among African Americans with
      diabetes.

PMID- 11567841
TI  - Health risk factors and occupation among Iowa workers.
AB  - BACKGROUND: Health behaviors represent major risks for premature morbidity and
      mortality. This study aimed to establish whether health risks varied
      substantially across occupational groups. METHODS: We focused on the 2223 Iowa
      Behavioral Risk Factor Surveillance System (BRFSS) subjects who reported, in
      1999, that they were currently working. RESULTS: Even after controlling for age
      and gender, we found significant associations between occupation and health risk
      factors. We found these associations among the different categories of health
      risk factors, including insurance/access, health conditions, preventive
      behaviors, and screening behaviors. CONCLUSIONS: The considerable differences in
      the prevalence of risk factors for chronic disease and injury across occupational
      groups in Iowa underscore the need for nationwide ongoing collection of
      occupational status in the BRFSS. These national data on the distribution of risk
      factors across occupations will support development of more targeted prevention
      interventions.

PMID- 11567842
TI  - Deer-vehicle crashes: extensive peak at 1 hour after sunset.
AB  - BACKGROUND: On-road encounters with animals resulted in 231 fatalities in the
      United States in 1999, and the annual number of deer-vehicle crashes (DVCs) has
      been estimated to total more than 500,000. Previous studies suggest that the
      number of DVCs is highest during the hours of dusk and dawn. However, these
      studies have not adequately taken into account the synchronization of visibility
      and animal behavior with sunset and sunrise. The goal of this study was to
      determine the temporal variation in the crash risk, so that this variation could
      be better taken into account by road users. METHODS: In Finland, the recorded
      times for 13,379 crashes with moose and 8191 crashes with white-tailed deer were
      adjusted to sunset and sunrise according to the location and date of occurrence.
      In addition, two sample distributions of traffic volume on public roads were
      adjusted to sunset. The DVC rate was computed as the proportion of number of
      crashes to traffic volume. RESULTS: The highest crash peak occurred 1 hour after
      sunset for both species of deer. The relative risk peaked at 30 times the
      seasonal daytime level of the crash rate for white-tailed deer in the fall and at
      over 60 times for moose in the summer. CONCLUSIONS: Drivers can effectively
      reduce their risk of DVCs by reducing speed and remaining alert for deer
      intrusions on the roadway during the most critical time of the day: after sunset.

PMID- 11567843
TI  - Using nurse practitioners for skin cancer screening: a pilot study.
AB  - BACKGROUND: Skin cancer screening has the potential to detect early precancerous
      lesions and may ultimately be important in reducing melanoma mortality. The
      purpose of this study was to evaluate the ability of trained nurse practitioners
      to accurately identify suspicious lesions in a clinical setting. METHODS: We
      identified five nurse practitioners who had no previous experience in evaluating
      skin lesions. Each nurse practitioner participated in a training program for skin
      cancer detection consisting of a workshop, clinical apprenticeship, and didactic
      lectures. RESULTS: Evaluation of nurse practitioner competency involved three
      assessments. First, the nurse practitioner's ability to distinguish benign and
      malignant lesions was assessed using clinical color slides. The sensitivity of
      all five nurse practitioners to refer benign and malignant lesions for
      dermatologic follow-up based on the slides was 100%, whereas the specificity
      ranged from 53% to 100%. Second, each nurse practitioner evaluated approximately
      25 different patients along with a single dermatologist. The nurse practitioner's
      ability to correctly refer patients with suspicious lesions for dermatologic
      follow-up was determined based on the dermatologist's assessment of need for
      referral. Results suggested a referral sensitivity and specificity ranging from
      67% to 100% and 62% to 100%, respectively. In the final clinical assessment, 30
      patients were independently examined by two dermatologists and four nurse
      practitioners. Using the consensus clinical diagnosis of the dermatologists as
      the gold standard, the nurse practitioner's sensitivity for detecting significant
      skin cancer lesions ranged from 50% to 100% and the detection specificity was 99%
      to 100%. CONCLUSIONS: These preliminary results have important implications for
      skin cancer screening efforts and suggest that nurse practitioners can be trained
      to accurately identify and triage suspicious lesions.

PMID- 11567844
TI  - Child hospitalization: an opportunity for parental smoking intervention.
AB  - BACKGROUND: Hospitalization with tobacco-related illness increases smokers'
      interest in cessation. Because parental smoking increases the child's risk of
      developing respiratory and other illnesses, a child's hospitalization might
      motivate a smoking parent to consider changing smoking behavior. It is unclear if
      parents would be receptive to smoking-cessation interventions at the time when
      their child is hospitalized. METHODS: In March 1999, parents of 298 consecutive
      children admitted to the medical services at Children's Hospital Boston were
      interviewed to determine the smoking status of household members. Smoking parents
      were invited to complete a 35-item questionnaire regarding personal smoking
      history and acceptability of three types of cessation interventions. RESULTS:
      Sixty-five smoking parents were identified among the 298 admissions; 62 of 65
      (95%) participated in the survey. Among respondents, only 15% had ever
      participated in any smoking-cessation program, and only 31% had ever used a
      medication to try to quit. Although 78% of parents were willing to speak with a
      counselor about their smoking while their child was in the hospital, and 74%
      would enroll in a telephone-based smoking-cessation program, only 26% were
      interested in a free program requiring travel back to the hospital. All parents
      believed that pediatricians should offer parental smokers the chance to
      participate in a smoking-cessation program. CONCLUSIONS: At the time of a child's
      hospitalization, parents are willing to enroll in smoking interventions that
      include in-hospital and telephone counseling but not to travel back to the
      hospital. A child's hospitalization may provide a unique opportunity to enroll
      parents who smoke into cessation programs.

PMID- 11567845
TI  - An evidence-based review of patient-centered behavioral interventions for
      hypertension.
AB  - INTRODUCTION: While behavioral interventions may be viewed as important
      strategies to improve blood pressure (BP), an evidence-based review of studies
      evaluating these interventions may help to guide clinical practice. METHODS: We
      employed systematic review and meta-analysis of the literature (1970-1999) to
      assess the independent and additive effects of three behavioral interventions on
      BP control (counseling, self-monitoring of BP, and structured training courses).
      RESULTS: Of 232 articles assessing behavioral interventions, 15 (4072 subjects)
      evaluated the effectiveness of patient-centered counseling, patient self
      monitoring of BP, and structured training courses. Pooled results revealed that
      counseling was favored over usual care (3.2 mmHg [95% CI, 1.2-5.3] improvement in
      diastolic blood pressure [DBP] and 11.1 mmHg [95% CI, 4.1-18.1] improvement in
      systolic blood pressure [SBP]) and training courses (10 mmHg improvement in DBP
      [95% CI, 4.8-15.6]). Counseling plus training was favored over counseling (4.7
      mmHg improvement in SBP [95% CI, 1.2-8.2]) and afforded more subjects
      hypertension control (95% [95% CI, 87-99]) than those receiving counseling (51%
      [95% CI, 34-66]) or training alone (64% [95% CI, 48-77]). CONCLUSIONS: Evidence
      suggests that counseling offers BP improvement over usual care, and that adding
      structured training courses to counseling may further improve BP. However, there
      is not enough evidence to conclude whether self-monitoring of BP or training
      courses alone offer consistent improvement in BP over counseling or usual care.
      The magnitude of BP reduction offered by counseling indicates this may be an
      important adjunct to pharmacologic therapy.

PMID- 11567846
TI  - Public health physicians: an endangered species.
AB  - BACKGROUND: Questions have arisen regarding the competency levels of the various
      professions within the public health sector, including those of physicians.
      Protection of the nation's health requires that physicians on the public health
      team be competent practitioners of both medicine and public health. Physicians
      practicing in this arena are required to possess a vast array of knowledge,
      skills, and attitudes to be effective contributors in the field. METHODS: Using
      focus groups of key informants in public health, the context of practice,
      inventory of required competencies, current competencies, and identified gaps in
      these competencies, measures to address the situation were identified and
      discussed. RESULTS: Recommendations from the focus groups include: use of
      distance-based learning, development of educational materials and programs, use
      of the American College of Preventive Medicine as a facilitator, improved
      remuneration, changes to the certification process, utilization of mentoring
      programs, introduction of new marketing strategies, use of professional
      publications, and increased governmental/agency support. Contributors to this
      endeavor are identified. CONCLUSIONS: While we strive to improve the physician
      workforce entering the field, creative strategies for continued lifelong learning
      are urgently needed to facilitate ongoing development of physicians in the
      current public health workforce. This situation presents a major research agenda
      for public health practice. Identification of the essential knowledge, skills,
      and attitudes for public health physicians is the first step toward narrowing
      gaps in required competencies.

PMID- 11567847
TI  - Opportunism in clinical preventive medicine.

PMID- 11567849
TI  - Ultrasound of the shoulder.
AB  - Ultrasound of the shoulder is a powerful and accurate method for the examination
      of the rotator cuff, biceps mechanism and the synovium. This article describes
      the anatomy, standard examination technique, indications, pitfalls and potential
      errors. It lists suggested imaging algorithms for a range of shoulder pathology.

PMID- 11567850
TI  - Ultrasound of the shoulder joint: non "rotator cuff" lesions.
AB  - Most of the papers in the literature are on rotator cuff lesions. This paper will
      deal with a somewhat forgotten part of the shoulder, the joint and the
      nontendinous structures around the joint. Since 1985, we have performed
      ultrasound examinations of the shoulder. We have collected many cases and some of
      them will be performed. The shoulder joint can be partly examined by ultrasound.
      We can get some information about joint effusions, humeral head cartilage, some
      part of the labrum, loose bodies, ganglions and fractures around the joint. The
      acromio-clavicular joint is also part of the examination, leading to diagnosis of
      sprains, osteoarthritis and dislocations. Non rotator cuff examination of the
      shoulder must be a routine part of the ultrasound examination of the shoulder.

PMID- 11567851
TI  - Ultrasound of the elbow.
AB  - This article describes the use of ultrasound (US) in the evaluation of the elbow.
      US is able to visualize several abnormalities affecting tendons, muscles,
      ligaments and bursae around the elbow joint as well as to delineate the nature of
      soft-tissue swelling, such as a space-occupying lesion or synovial enlargement.
      Occult fractures, osteophytes and intra-articular loose bodies can be depicted
      with this technique as well. At the cubital tunnel, US allows accurate imaging of
      the ulnar nerve and to document changes that occur in compressive syndromes. Over
      other imaging modalities, US offers several key advantages, including cost
      effectiveness, availability and ability to perform a dynamic examination of
      tendon movement and joint motion. With continued experience, it is likely that
      the use of US will increase further with regards to evaluation of soft-tissue
      abnormalities of the elbow.

PMID- 11567852
TI  - Ultrasound of the hand.
AB  - A recent development of high resolution transducers has increased the possibility
      to evaluate the most superficial body structures. The assessment of the normal
      anatomy and of the pathological changes of the hand and the wrist has become
      popular among musculoskeletal sonologists and nowadays ultrasound is considered
      one of the first line imaging techniques in the assessment of this district.
      Ultrasound must always be performed after a standard radiograph since the
      association of the two techniques can diagnose a wide variety of disorders. Some
      lesions however cannot be detected and require more invasive and expensive
      modalities (CT, MRI, CT and MRI arthrography). The goal of this article is to
      present the ultrasound appearance of inflammatory and traumatic diseases of the
      hand and wrist as well as the findings in entrapment neuropathies and soft tissue
      tumors.

PMID- 11567853
TI  - Ultrasound of the hip.

PMID- 11567854
TI  - Paediatric hip--ultrasound screening for developmental dysplasia of the hip: a
      review.
AB  - This paper will try to deal with the following questions: Which is the correct
      screening model for the developmental dysplasia of the hip (DDH)? What is the
      clinical significance of "sonographic" DDH? Can overtreatment produced by
      ultrasound (US) screening cause a waste of resources and eventually morbidity? We
      reviewed the literature since January, 1996 through December, 2000. To compare
      our experience with the literature, we analysed the results of the US
      examinations of the hip performed in our Institute. Over 4 years of US screening
      11326 infants (22652 hips), aged 3 days to 4 months, were examined consecutively.
      Sonographic hip findings were abnormal in 531 infants (4.7%). The screening
      showed 381 subjects (3.36% of the population) with a type IIa hip (bilateral or
      unilateral); 65% of these infants were normal at follow up and only 35% worsened.
      On the whole we treated 282 infants (2.5%). No open reduction was performed.
      Avascular necrosis appeared in 2/282 treated cases (1.06%). We support the
      routine generalised US screening of neonatal hips. The excess of doubtful cases
      and, consequently, of the extra referrals may be limited, and the overtreatment
      decreased to the lowest rates reported by optimisation of everyone's approach.

PMID- 11567855
TI  - Ultrasound of the knee.

PMID- 11567856
TI  - Ultrasound of the ankle.
AB  - Because of their size and superficial location the ankle tendons can be well
      evaluated with ultrasound (US). The excellent definition of the modern high
      frequency probes allows us to consider US the technique of first choice in their
      assessment. Basic US appearances correlate well with the MRI findings. Since US
      can diagnose most tendon disorders including tendinopathies, tears, dislocations
      and enthesopathies MRI is less often utilized. US can easily depict the main
      ankle ligaments. The basic US appearance of ligament tears is well known. US can
      be considered an inexpensive and accurate technique in the evaluation of ankle
      sprains.

PMID- 11567857
TI  - Is the nucleus in need of translation?

PMID- 11567873
TI  - Endocytosis without clathrin coats.
AB  - Endocytosis is involved in an enormous variety of cellular processes. To date,
      most studies on endocytosis in mammalian cells have focused on pathways that
      start with uptake through clathrin-coated pits. Recently, new techniques and
      reagents have allowed a wider range of endocytic pathways to begin to be
      characterized. Various non-clathrin endocytic mechanisms have been identified,
      including uptake through caveolae, macropinosomes and via a separate constitutive
      pathway. Many markers for clathrin-independent endocytosis are found in detergent
      resistant membrane fractions, or lipid rafts. We will discuss these emerging new
      findings and their implications for the nature of lipid rafts themselves, as well
      as for the potential roles of non-clathrin endocytic pathways in remodeling of
      the plasma membrane and in regulating the membrane composition of specific
      intracellular organelles.

PMID- 11567874
TI  - The centrosome in vertebrates: more than a microtubule-organizing center.
AB  - The somatic cells of all higher animals contain a single minute organelle called
      the centrosome. For years, the functions of the centrosome were thought to
      revolve around its ability to nucleate and organize the various microtubule
      arrays seen in interphase and mitosis. But the centrosome is more than just a
      microtubule-organizing center. Recent work reveals that this organelle is
      essential for cell-cycle progression and that this requirement is independent of
      its ability to organize microtubules. Here, we review the various functions
      attributed to the centrosome and ask which are essential for the survival and
      reproduction of the cell, the organism, or both.

PMID- 11567875
TI  - COP9 signalosome revisited: a novel mediator of protein degradation.
AB  - The COP9 signalosome is an evolutionarily conserved multiprotein complex that was
      first identified as an essential complex that represses light-regulated
      development in Arabidopsis. The COP9 signalosome has similarity to the lid of the
      19S regulatory particle of the 26S proteasome and has recently been shown to
      interact with SCF-type E3 ubiquitin ligases. Although its precise role in the
      process of protein degradation remains to be established, the COP9 signalosome is
      a positive regulator of E3 ubiquitin ligases that functions at least in part by
      mediating the deconjugation of the NEDD8/RUB-modification from the cullin subunit
      of SCF-type E3 complexes. Here, we discuss these recent findings, which add an
      additional component to the biology of substrate-specific protein degradation.

PMID- 11567876
TI  - Integrating stress-response and cell-cycle checkpoint pathways.
AB  - The DNA integrity checkpoint and stress kinase (SAPK/JNK and p38) pathways
      function to modulate cell-cycle, apoptotic and transcriptional responses to
      stress. Although initially considered to function independently, recent advances
      indicate a number of links between the stress-response and checkpoint pathways.
      Here, we consider the relationship between the stress-response and checkpoint
      pathways and how they interact to modulate cell-cycle control.

PMID- 11567877
TI  - Alastair Valentine Philp.

PMID- 11567878
TI  - Biological effects of radiation: role of electron microscopy.

PMID- 11567879
TI  - Collagen as a model for the study of radiation induced side effects: use of image
      processing.
AB  - Collagen can be used as a model system for studying the effects of radiation on a
      protein. Quantitative studies of collagen fibrils from electron-optical images
      from radiated and non-radiated material can produce information not only about
      the structural effects produced by radiation, but also about the actual part of
      the fibril being affected.

PMID- 11567880
TI  - Electromagnetic stimulation on the bone growth using backscattered electron
      imaging.
AB  - The events at the hydroxyapatite implant material/tissue interface following
      electromagnetic stimulation were studied in the rabbit. Two kinds of
      hydroxyapatite were used: natural (NA) and synthetic (HA) both with a grain size
      of <50 microm. Bone defects, artificially created in rabbit tibiae, were filled
      with the material examined. One group of animals was exposed immediately after
      surgery and every 12h thereafter to 30-min treatments with electromagnetic fields
      (PEMFs). A second group was used as a control (untreated). Two and 4 weeks after
      implantation, animals were sacrificed and bone samples processed for LM, TEM and
      SEM using a backscatter electron detector for the evaluation of bone growth. This
      study indicates that HA has more osteoconductivity than NA, and shows that PEMF
      treatment results in a benefit in accelerating bone formation at early time
      periods.

PMID- 11567881
TI  - Bystander effects caused by nonuniform distributions of DNA-incorporated (125)I.
AB  - A three-dimensional tissue culture model was used to investigate the biological
      effects of nonuniform distributions of DNA-incorporated (125)I in mammalian
      cells. Chinese hamster V79 cells were labeled with (125)I-iododeoxyuridine, mixed
      with unlabeled cells, and multicellular clusters ( approximately 1.7 mm in
      diameter) were formed by gentle centrifugation. The highly localized energy
      deposition caused by (125)I decays results in very high equivalent doses
      delivered to the labeled cells and low equivalent doses delivered to the
      unlabeled cells. The clusters were assembled and then maintained at 10.5 degrees
      C for 72 h to allow (125)I decays to accumulate, dismantled, and the cells were
      plated for colony formation. When 100% of the cells were labeled, the survival
      fraction was exponentially dependent on the mean radioactivity per labeled cell.
      A two-component exponential response was observed when either 50 or 10% of the
      cells were labeled. These experimental data, coupled with theoretical dosimetry
      calculations, indicate that bystander effects play an important role in the
      killing of unlabeled cells when nonuniform distributions of DNA-incorporated
      (125)I are present.

PMID- 11567882
TI  - Radiation-induced kidney injury: a role for chronic oxidative stress?
AB  - Kidney irradiation clearly leads to a progressive reduction in function
      associated with concomitant glomerulosclerosis and/or tubulointerstitial
      fibrosis. However, the particular cell types, mediators and/or mechanisms
      involved in the development and progression of radiation nephropathy remain ill
      defined. Angiotensin II (Ang II) plays a major pathogenic role; administration of
      Ang II blockers markedly abrogates the severity of radiation nephropathy in
      experimental models. Both ionizing radiation and Ang II signal via generation of
      reactive oxygen species (ROS). Thus, we hypothesized that localized kidney
      irradiation might lead to a chronic oxidative stress. In view of the difficulty
      in measuring ROS in vivo we adopted an indirect immunohistochemical approach in
      which we used a monoclonal antibody specific for 8-hydroxy-2'-deoxyguanosine (8
      OHdG), one of the most commonly used markers of DNA oxidation. The right kidney
      of 7-8 week-old male Sprague-Dawley rats was removed. Five to 6 weeks later the
      remaining hypertrophied kidney was irradiated with single doses of 0-20.0 Gy X
      rays. Groups of rats, three per dose, were killed at 4, 8, 16 and 24 weeks post
      irradiation, their kidneys fixed, and sections stained with the 8-OHdG-specific
      antibody N45.1. For quantitation of glomerular DNA oxidation with the N45.1
      antibody stained sections, 50 glomeruli/animal were counted. The presence of any
      intensely stained nuclei within the glomerular tuft was scored as positive.
      Quantitation of tubular DNA oxidation employed a 10 x 10 point ocular grid.
      Sections were examined at 400 magnification; 250 tubular profiles were counted.
      All tubules with any nuclear staining were scored as positive.Sham-irradiated
      kidneys showed little evidence of DNA oxidation over the experimental period. In
      contrast, localized kidney irradiation led to a marked, dose-independent increase
      in glomerular and tubular cell nuclear DNA oxidation. This increase was evident
      at the first time point studied, i.e. 4 weeks after irradiation, and persisted
      for up to 24 weeks postirradiation. DNA oxidation in the irradiated kidney was
      only seen in apparently viable glomerular and tubular cells. Thus, while from 16
      to 24 weeks post-irradiation structural alterations had progressed to glomerular
      sclerosis and tubular atrophy, positive staining for 8-OHdG was not observed in
      severely atrophic tubules. Similarly, fewer positive staining cells were noted in
      glomeruli undergoing sclerosis, while none were seen in totally sclerotic
      glomeruli. These data support the hypothesis that renal irradiation is associated
      with a chronic and persistent oxidative stress.

PMID- 11567883
TI  - Influence of X-ray on the autophagic-lysosomal system in rat pancreatic acini.
AB  - Lysosomes have an important role in radiation injury of cells and tissues.
      Activation of autophagy is frequently observed in different types of pathological
      tissue degeneration. In radiation response it increases in some cases, and
      lysosomes are responsible for regulated degradation of the autophagic vacuoles.
      Lysosomes are also involved in ionizing radiation induced cell death. In
      apoptosis lysosomes degrade content of the phagocytotic vacuoles derived from
      engulfed apoptotic blebs. On the other hand lysosomal enzymes discharged from
      disintegrated cells have a key role in induction of necrotic changes. In this
      work we investigate autophagy and lysosomal protein degradation in the relatively
      radiation insensitive exocrine pancreatic acini in vivo and in vitro. Type of
      cell death induced by X-ray was also examined in relation to the changes of the
      lysosomal processes. In 5h after 16 Gy in vivo whole body irradiation we observed
      significant increase in the cytoplasmic volume fraction of autophagic vacuoles
      and in the number of apoptotic cells in vivo. But in the acini isolated from
      irradiated rats we could not detect a change in the lysosomal degradation of
      intracellular proteins. Therefore irradiation probably influences the autophagy
      in an earlier step than lysosomal degradation. Extended necrotic lesions were not
      observed in vivo as long as 48 h. Isolated pancreatic acini usually contain more
      autophagic vacuoles than in vivo, but we could not observe additional increase in
      autophagy after 8 Gy, in vitro irradiation. Lysosomal degradation of
      intracellular proteins was also unaltered after 8 Gy, in vitro irradiation. Other
      biochemical functional parameters of the isolated pancreatic acini, like protein
      synthesis and amylase secretion were not changed either after 8 Gy, in vitro X
      ray treatment. These results indicate that pancreatic acinar cells in vitro have
      a high tolerance to irradiation. The observed in vivo radiation induced changes
      of the exocrine pancreas are possibly indirectly induced by injuries of more
      sensitive mechanisms.

PMID- 11567884
TI  - Pilocarpine treatment of xerostomia in head and neck patients.
AB  - We studied the effect of pilocarpine hydrochloride, a parasympathicomimetic
      agent, on major salivary gland output and subjective responses in 40 patients
      with salivary hypofunction. Pilocarpine increased salivary output or gave
      significant symptomatic relief in 21 of the 40 patients. The women fared better
      than the men. Side effects were uncommon, were generally mild, and caused no
      treatment interruption. These results indicate that pilocarpine is effective in
      relieving the signs and symptoms of postradiation xerostomia.

PMID- 11567885
TI  - Insights into UV-induced apoptosis: ultrastructure, trichrome stain and spectral
      imaging.
AB  - Nuclear substructures associated with apoptosis in HeLa cells have been examined
      using light-microscopic morphometry, trichrome staining, spectral imaging and
      transmission electron microscopy. This detailed analysis reveals several sites
      where alterations in the normal cellular ultrastructure occur during apoptotic
      progression. To correlate these ultrastructural changes with the underlying
      molecular processes, we have characterized and quantified apoptotic cell
      morphology with and without inhibition of two caspases, which are key effectors
      of the apoptotic program. Using this analysis, early apoptotic events included:
      (a) the segregation of nucleolar components, a diminished granular component, and
      a reduction in number but increase in size of fibrillar centers, (b) an increase
      in the number of cytoplasmic ribosomes and (c) a very minimal increase in the
      amount of peripherally condensed DNA. Apoptosis progressed with: (a) an increase
      in the number of perichromatin granules and perichromatin fibrils, (b) a
      reduction in number of interchromatin granule centers concomitant with an
      increase in their size, (c) partial digestion and circumferential condensation of
      the DNA at the nuclear membrane and (d) rounding of the cytoplasm with an
      increase in organellar density and shrinkage in cell size. Endstage apoptotic
      cells showed: (a) one (or two) very large pools of incompletely digested DNA, (b)
      one (or two) very large interchromatin granule centers, (c) an increased number
      of perichromatin granules which were distanced from DNA and often closely apposed
      to the nucleolus, (d) formation of unusually condensed, highly coiled
      perinucleolar bodies and (e) blebbing of highly dense cytoplasm. In HeLa cells
      treated with UV and inhibitors of caspase 1 and 3, the length of time from early
      apoptosis to the formation of apoptotic bodies was greatly extended. Inhibiting
      caspase activity: (a) prevented the pooling of DNA, (b) retarded the formation of
      large interchromatin granule centers, (c) increased the number of perichromatin
      granules, (d) produced disassembly of the nucleolus, (e) prevented the formation
      of highly coiled perinucleolar bodies, and (f) caused vacuolization in the cell
      center and a unipolar blebbing of the cytoplasm. Spectral imaging in conjunction
      with serial section electron microscopy confirmed the staining specificities of
      the condensed DNA, of the large condensed interchromatin granule centers, and of
      the nucleoli. The results indicate that the interface between the components of
      the chromatin domain and the interchromatin space is a critical site of caspase
      activity in apoptosis, and precedes other events such as internucleosomal DNA
      degradation.

PMID- 11567886
TI  - Morphological aspects of ionizing radiation response of small intestine.
AB  - Knowledge of the acute and late ionizing radiation exposure damage to the
      gastrointestinal tract, particularly injury of the small intestine, is of great
      significance in radiotherapy, as is management of accidental radiation exposure.
      Irradiation (X-ray, neutron, cobalt gamma) induces a series of events in this
      rapidly renewing tissue resulting in the well-known symptoms of the
      gastrointestinal (GI) radiation syndrome, such as GI haemorrhage, endotoxemia,
      bacterial infection, anorexia, nausea, vomiting, diarrhoea, and loss of
      electrolytes and fluid. In spite of the significant advances that have occurred
      in research on underlying mechanisms over the last two decades, the overall
      etiology and pathogenesis of the GI-syndrome still remains unclear. Currently, to
      our knowledge, these symptoms are probably due to a rapid modification of the
      intestinal motility and to the structural alteration of the intestinal mucosa
      (cell loss and altered crypt integrity). Several evidences suggest that radiation
      induced dysfunctions and structural changes of this organ (either changes in
      subcellular, cellular, and histological structure) are mediated by concerted and
      interrelated changes of a plethora of various extracellular mediators and their
      intracellular messengers. The aim of this review is to summarize our current
      knowledge about the pathomorphology and cell biology of the ionizing radiation
      response of the GI tract with a focus on the small intestine.

PMID- 11567887
TI  - Effects of ultraviolet radiation on plant cells.
AB  - Recent measurements of ozone levels have led to concern that the stratospheric
      ozone layer is being depleted as a result of contamination with man-made
      chlorofluorocarbons. Concomitantly, the amounts of solar UV-B radiation reaching
      the Earth's surface is increasing. UV-B radiation has been shown to be harmful to
      living organisms, damaging DNA, proteins, lipids and membranes. Plants, which use
      sunlight for photosynthesis and are unable to avoid exposure to enhanced levels
      of UV-B radiation, are at risk. Thus, mechanisms by which plants may protect
      themselves from UV radiation are of particular interest. This review will
      summarizes the main aspects of ultraviolet radiation on plants at physiological
      and biochemical level, with particular emphasis on protective structures and
      mechanisms.

PMID- 11567888
TI  - Effect of gamma and UV-B/C radiation on plant cells.
AB  - The biological effect of gamma-rays is based on the interaction with atoms or
      molecules in the cell, particularly water, to produce free radicals, which can
      damage different important compounds of plant cell. The UV-B/C photons have
      enough energy to destroy chemical bounds, causing a photochemical reaction. The
      biological effect is due to these processes. This paper is focused on the
      structural and biochemical changes of the cell wall and plastids after gamma
      and/or UV-B irradiation. Gamma-rays accelerate the softening of fruits, causing
      the breakdown of middle lamella in cell wall. They also influence the plastid
      development and function, such as starch-sugar interconversion. The penetration
      of UV-B light into the cell is limited, while gamma-rays penetrate through the
      cells. For this reason, UV-B light has a strong effect on surface or near-to
      surface area in plant cells. UV-B radiation influences plastid structure (mostly
      thylakoid membranes) and photosynthesis. Some kinds of pigments, such as
      carotenoids, flavonoids save plant cells against UV-B and gamma irradiation.
      Plant cells are generally ozone sensitive. The detoxifying systems operate at the
      cellular level. Methods for studying structural changes in plant cells develop in
      direction to molecular biology, combined with immunoassays and new microscopical
      techniques. Nowadays, UV-B radiation is undergoing much research, being an
      environmental factor which causes damage to both humans and plant cells.

PMID- 11567889
TI  - Biological infrared imaging and sensing.
AB  - A variety of thermoreceptors are present in animals and insects, which aid them
      in hunting, feeding and survival. Infrared (IR) imaging pit organs in Crotaline
      and Boid snakes enable them to detect, locate and apprehend their prey by
      detecting the IR radiation they emit. IR pit organs of common vampire bats
      (Desmodus rotundus) enable them to detect IR radiation emitted by blood-rich
      locations on homeothermic prey. The beetle Melanophila acuminata locates forest
      fires by IR-detecting pit organs in order to lay their eggs in freshly killed
      conifers. Thermoreceptors located in the wings and antennae of darkly pigmented
      butterflies (Pachliopta aristolochiae and Troides rhadamathus plateni) protect
      them from heat damage while sun basking. Blood-sucking bugs (Triatoma infestans)
      are speculated to possess thermoreceptors, which enable them to perceive the
      radiant heat emitted by homeothermic prey and estimate its temperature at a
      distance. This is a review of the diverse types of biological thermoreceptors,
      their structure and function, and how electron microscopy has been instrumental
      in determining their ultrastructure.

PMID- 11567890
TI  - Control genes in quantitative molecular biological techniques: the variability of
      invariance.
AB  - The measurement of transcript levels constitutes the foundation of today's
      molecular genetics. Independent of the techniques used, quantifications are
      generally normalised using invariant control genes to account for sample
      handling, loading and experimental variation. All of the widely used control
      genes are evaluated, dissecting different methodological approaches and issues
      regarding the experimental context (e.g. development and tissue type).
      Furthermore, the major sources of error are highlighted when applying these
      techniques. Finally, different approaches undertaken to assess the invariance of
      control genes are critically analysed to generate a procedure that will help to
      discern the best control for novel experiments.

PMID- 11567891
TI  - High levels of docosahexaenoic acid (22:6n-3)-containing phospholipids in high
      frequency contraction muscles of hummingbirds and rattlesnakes.
AB  - Phospholipids containing docosahexaenoic acid (22:6n-3) have been proposed to be
      required as conformational cofactors for the functional assembly of membrane
      proteins such as rhodopsin, ion pumps and the various complexes of the
      mitochondrial electron transport chain (Infante, 1987, Mol. Cell. Biochem. 74,
      111-116; Infante and Huszagh, 2000, FEBS Lett. 468, 1-5). This hypothesis
      predicts that high-frequency contraction muscles, which are endowed with a high
      content of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and mitochondrial
      respiration enzymes, would have higher concentrations of 22:6n-3-containing
      phospholipids when compared with other muscles in the same species known to have
      a much lower contraction frequency. We have analyzed the fatty acid composition
      of ruby-throated hummingbird (Archilochus colubris) pectoral and leg muscles and
      of rattlesnake (Crotalus atrox) shaker and ventral muscles. We have found that
      hummingbird pectoral muscles, which are high contraction frequency muscles with
      the highest known respiratory rate among vertebrates, have a 22:6n-3
      concentration of 20.8% vs. 4.9% for the low frequency leg muscles. Similarly,
      rattler muscles in rattlesnakes, also high contraction frequency muscles, have a
      higher 22:6n-3 concentration than that of their ventral muscles (15.1% vs. 10.6%,
      respectively). These results are consistent with a specific molecular role for
      22:6n-3-containing phospholipids, as proposed.

PMID- 11567892
TI  - Avian air sac and plasma proteins that bind surface polysaccharides of
      Escherichia coli O2.
AB  - Some serovars of Escherichia coli, mainly O2 and O78, are responsible for air sac
      and systemic infections in farm-raised turkeys (Meleagris gallopavo) and chickens
      (Gallus gallus). We looked in air sac surface fluid from young turkeys to
      identify proteins that bind surface polysaccharides of pathogenic respiratory E.
      coli O2. Turkey air sac surface fluid was subjected to affinity chromatography on
      Toyopearl AF-Epoxy-650M, coupled with either lipopolysaccharide (LPS) or lipid
      free polysaccharide (LFP) purified from an avian pathogenic E. coli O2 isolate. A
      multimeric protein termed lipid-free polysaccharide binding protein-40 (LFPBP-40)
      composed of six covalently associated subunits of approximately 40 kDa was
      isolated by elution from LFP by EDTA or L-rhamnose. An analogous protein in air
      sac fluid proteins bound to intact E. coli O2 and eluted with L-rhamnose or N
      acetylglucosamine (GlcNAc). The N-terminal amino acid sequence of LFPBP-40
      DINGGGATLPQHLYLTPDV was related to the N-terminus of fragment 3 of a partially
      characterized human protein possessing T cell stimulation activity in synovial
      membrane of rheumatoid arthritis patients. However, endogenous amino acid
      sequences were unrelated to other known proteins. LFPBP-40 was immunoreactively
      distinct from pulmonary collectins and ficolins. These studies demonstrate a
      novel avian respiratory soluble lectin that can bind surface polysaccharides of
      pathogenic E. coli responsible for respiratory disease.

PMID- 11567893
TI  - Major and c-series gangliosides in lenticular tissues: mammals to molluscs.
AB  - Gangliosides of eye lenses were examined in mammals (rat, rabbits, pig, cow),
      bird (chicken), reptile (terrapin), amphibian (bullfrog), bony fish (red sea
      bream, bluefin tuna, bonito, Pacific mackerel) and molluscs (common squid,
      Pacific octopus). Besides the fact that GM3 was the common ganglioside species,
      the composition of major gangliosides in mammalian eye lenses significantly
      differed from each other. While gangliotetraose gangliosides were abundant in rat
      eye lens, they did not constitute major components in porcine and bovine tissues.
      The c-series ganglioside GT3 was expressed in rat eye lenses but were practically
      absent in other mammalian tissues. The composition of major gangliosides in eye
      lenses of lower animals varied from species to species, whereas c-series
      gangliosides were consistently expressed, showing similar compositional profiles.
      Our results demonstrate the species-specific compositions of lenticular
      gangliosides. Evidence was also provided suggesting that eye lenses of common
      squid (Todarodes pacificus) and Pacific octopus (Octopus vulgaris) express
      gangliosides including gangliotetraose species and c-series gangliosides.

PMID- 11567894
TI  - Rapid action of glucocorticoids on branchial ATPase activity in Oreochromis
      mossambicus: an in vivo and in vitro study.
AB  - The rapid action of cortisol and corticosterone on branchial Na(+)-K(+) ATPase,
      Ca(2+) ATPase activity and Na(+), K(+) and Ca(2+) ion contents was studied both
      in vivo and in vitro employing transcription inhibitor actinomycin D in
      Oreochromis mossambicus. Cortisol and corticosterone administration had
      significantly increased the activity of branchial Na(+)-K(+) ATPase and Ca(2+)
      ATPase in vivo after 30 min of injection, and the trend continued for 60 and 120
      min for cortisol. The ionic contents were also significantly increased after 30
      min in vivo. Na(+)-K(+) ATPase activity was significantly increased 5 min after
      hormone application in the in vitro system. Actinomycin D did not inhibit the
      effect of glucocorticoids on ATPase activity both in vivo and in vitro. It is
      concluded from the present study that cortisol and corticosterone produced a
      rapid stimulatory effect on branchial ATPase activity and ions in O. mossambicus
      both in vivo and in vitro. This effect could be due to a non-genomic action of
      these hormones since the enzyme activity was insensitive to actinomycin D.

PMID- 11567895
TI  - Digestive proteinases of red shrimp Pleoticus muelleri (Decapoda, Penaeoidea):
      partial characterization and relationship with molting.
AB  - The present study describes the activity and some characteristics of proteinases
      in the hepatopancreas of red shrimp Pleoticus muelleri during the different
      stages of the molting cycle. Proteolytic activity was highest between pH 7.5 and
      8. The hepatopancreatic protein content in the premolt stage was higher than in
      the other stages of the molting cycle (P<0.05). No significant differences were
      found in total proteolytic activity in the hepatopancreas when comparing molting
      stages. The proteolytic activity of the P. muelleri hepatopancreas enzyme
      preparations is the main responsibility of serine proteinases. TLCK, a trypsin
      inhibitor, reduced azocasein hydrolysis between 26% (intermolt) and 37%
      (premolt). TPCK, a chymotrypsin inhibitor, did not decrease hydrolytic activity,
      except for in postmolt. Low trypsin and chymotrypsin activities were found during
      intermolt, and increased in postmolt. The electrophoretogram of the enzyme
      extracts shows 12 bands of activity during intermolt (from 16.6 to 53.1 kDa).
      Some fractions were not detected in the postmolt and premolt stages. Three low
      molecular weight trypsin forms (17.4, 19.1 and 20 kDa) were found in all molting
      stages. One band of chymotrypsin (21.9 kDa) was observed in all molting stages.
      High molecular mass active bands (66-205 kDa) could not be characterized with
      inhibitors. Comparison of the protease-specific activity of the hepatopancreas of
      some species indicated a relationship between digestive enzyme activity and
      feeding habits of the shrimp. Omnivorous shrimp, such as Penaeus vannamei (syn:
      Litopenaeus vannamei) and Penaeus monodon, showed higher protease activity than
      the carnivorous shrimp, Penaeus californiensis (syn: Farfantepenaeus
      californiensis) and P. muelleri. In fact, the enzymatic activity in the
      hepatopancreas of P. muelleri showed variations in relation to feeding habit and
      molting cycle.

PMID- 11567896
TI  - Ontogenetic changes in enzyme activities associated with energy production in the
      spiny lobster, Jasus edwardsii.
AB  - The larval life of the spiny lobster Jasus edwardsii is one of the longest and
      most complex of any marine organism and is poorly understood due to the
      difficulty of studying cryptic, pelagic organisms. Hence, the capacity for active
      swimming in the phyllosoma, puerulus and juvenile stages and the use of possible
      metabolic fuel reserves was inferred from a number of enzyme activities,
      including citrate synthase, lactate dehydrogenase, and HOAD. High activities of
      CS and LDH in abdominal tissues of Stage 11 phyllosoma and pueruli are consistent
      with a capacity to commence active on-shore movement. The activities of LDH and
      HOAD showed positive allometry while CS was independent of body mass. The body
      mass dependence of LDH activity may reflect the developing ability of the lobster
      to initiate brief escape manoeuvres, and the scaling of HOAD reflects an
      increased use of lipid fuel reserves. Aerobic enzyme activities were higher in
      abdominal tissues than in cephalic tissues of pelagic pueruli, but high
      activities appear in the cephalic tissues of juveniles. These changes mirror a
      developmental shift in activity from pelagic oceanic swimming to a benthic
      existence on the seabed of the near shore. The low LDH activity in pueruli
      confirmed previous findings that they have limited feeding capacity, with
      carbohydrate contributing little towards the major energy reserves. The highest
      LDH activities occur in the abdominal muscles of juveniles and correlate with
      rapid tail-flicking escape behaviour. The activities of HOAD increased throughout
      development, and in the abdominal tissues of juveniles, may reflect lipid
      transformation and accumulation as an energy reserve. Enzyme activities,
      therefore, provide useful information concerning migratory behaviour that is
      presently unavailable from ecological studies.

PMID- 11567897
TI  - Qualitative and quantitative differences in cuticular hydrocarbons between
      laboratory and field colonies of Pogonomyrmex barbatus.
AB  - Ants held in the laboratory and field ants of the species Pogonomyrmex barbatus
      have quantitative differences in their cuticular hydrocarbons and a qualitative
      difference in their methyl-branched hydrocarbons. Laboratory-held workers showed
      twice the hydrocarbon content as field ants. This difference was mainly due to
      higher amounts of straight-chain alkanes and methyl-branched alkanes in
      laboratory ants, whereas the proportion of the alkenes remained the same for both
      groups. In addition to the absence of some hydrocarbons in the field colonies,
      one of the methyl-branched hydrocarbons differed in amount and branching pattern
      between the two groups of ants. Whereas, notable peaks of 2-methylalkanes were
      identified in ants kept in the laboratory, these compounds could not be
      identified in ants living in their natural habitat. However, a trace amount of 4
      methyltriacontane was found in lieu of the 2-methyltriacontane counterpart in
      field ants. Possible explanations for both qualitative and quantitative
      differences are discussed.

PMID- 11567898
TI  - Dehydroepiandrosterone (DHEA) stimulates glucose uptake in rat adipocytes:
      activation of phospholipase D.
AB  - We examined the effect of dehydroepiandrosterone (DHEA) on glucose uptake and
      phospholipase D (PLD) activation in rat adipocytes. DHEA (1 microM) provoked a
      twofold increase in [3H]2-deoxyglucose (DG) uptake for 30 min. Incorporation of
      [3H]glycerol into diacylglycerol was increased 150% above basal level for 20 min
      after stimulation with 1 microM DHEA. DHEA increased PLD activity, measured by
      the incorporation into [3H]phosphatidylethanol in [3H]palmitate labelled rat
      adipocytes, or by [3H]choline release in [methyl-(3)H]choline labeled rat
      adipocytes. Our results suggest that DHEA stimulates glucose uptake with
      activation of PLD in rat adipocytes.

PMID- 11567899
TI  - Cryoprotective role of polyols independent of the increase in supercooling
      capacity in diapausing adults of Pyrrhocoris apterus (Heteroptera: Insecta).
AB  - Diapausing cold-acclimated adults of the bug Pyrrhocoris apterus accumulate four
      'winter' polyols, ribitol, sorbitol, mannitol and arabinitol, in total
      concentrations of up to 100 mM. The accumulation started only when the
      temperatures dropped below a threshold of +5 degrees C in laboratory acclimated
      insects. The supercooling capacity (SCP) was not affected by polyol accumulation
      and remained constant at approximately -17 degrees C. Cold hardiness, measured as
      survival time (Lt50) at -15 degrees C, increased from approximately 1 day to
      approximately 1 week in parallel with polyol accumulation. There was a tight
      correlation (r=0.98) between the concentration of 'winter' polyols in haemolymph
      and Lt50(-15). When a mixture of ribitol and sorbitol was injected into the
      haemolymph of the bugs acclimated to +5 degrees C, the concentration of polyols
      increased from 2.5 to 83.1 mM in haemolymph, or from 0.07 to 6.61 microg/mg of
      fresh weight in the whole body, the SCP remained unchanged and survival after
      exposure to -14 degrees C for 3 days increased approximately three-fold in
      comparison to untreated controls. Such results were interpreted as evidence for
      the cryoprotective role of accumulated polyols independent of the depression of
      SCP. Acclimation protocol using thermoperiod, mimicking daily temperature
      oscillations, resulted in moderately lower SCP, higher sum of polyols accumulated
      and significantly longer Lt50(-15) than at acclimation protocol with constant
      temperatures.

PMID- 11567900
TI  - Purification and characterization of alpha-L-fucosidases from Streptomyces sp.
      OH11242.
AB  - alpha-L-Fucosidases were found in the culture fluid of Streptomyces sp. OH11242
      grown with porcine gastric mucin (PGM) as the sole carbon source. The alpha-L
      fucosidases were purified by ammonium sulfate precipitation followed by
      chromatography on Sepharose CL-4B, hydroxyapatite, Resource Q and Mono Q. Two
      enzyme fractions, termed Fase-I and Fase-II, were obtained, each bearing
      different substrate specificity. Fase-I hydrolyzed fucose residues from fucose
      containing oligosaccharide chains on PGM, but not p-nitrophenyl alpha-L-fucoside
      (Fucalpha-O-PNP). In contrast, Fase-II cleaved fucose from Fucalpha-O-PNP, but
      not fucose-containing oligosaccharides on PGM. Fase-I also hydrolyzed the alpha1
      2 fucosidic linkage in various oligosaccharides, but not alpha1-3 and alpha1-4
      fucosidic linkages. Fase-II was separated into two fractions, Fase-IIa and -IIb
      by Mono Q chromatography, Fase-IIb hydrolyzed alpha1-3 and alpha1-4 fucosidic
      linkages, but not alpha1-2 fucosidic linkages, while Fase-IIa hydrolyzed none of
      them. Fase-I was purified to homogeneity by SDS-polyacrylamide gel
      electrophoresis, the molecular mass was estimated to be approximately 59000 and
      76000 Da by SDS-PAGE and gel-permeation chromatography, respectively. The optimum
      pH for Fase-I activity was 5.5-6.0. These fucosidases with different substrate
      specificities might be useful to reveal the physiological role of fucose
      containing oligosaccharides in the gastric mucins.

PMID- 11567901
TI  - Isolation and characterization of the retinoblastoma protein from fish.
AB  - The retinoblastoma (Rb) gene represents the first tumor suppressor gene
      characterized. The encoded protein, pRb, plays a crucial role in cell cycle
      control, preventing malignant cell proliferation. Recently, homologues of the Rb
      gene have been isolated in fish and the pocket domain, which is central to Rb
      function, was conserved. In our studies, using coelocanth (Latimeria chalumnae),
      rainbow trout (Oncorhynchus mykiss), medaka (Oryzias latipes) and English sole
      (Parophrys vetulus), we have developed a simple protocol for the isolation of the
      Rb tumor suppressor protein and determined its' tissue and cellular localization.
      Fish Rb proteins display apparent molecular weights in the range of 100-110 kDa,
      similar to the human pRb. The protein was detected in all tissues examined,
      consistent with the proteins' universal role in cellular signalling. An
      interesting pattern of immunoreactive bands was detected in each of the cells'
      two main compartments, suggesting differential proteolysis. Immuno-analysis of
      the pRb in trout liver tumor material revealed an additional Rb reactive product
      that was absent in normal liver cell extracts.

PMID- 11567902
TI  - Isolation and expression of cathepsin B cDNA in hemocytes during metamorphosis of
      Bombyx mori.
AB  - By using RT-PCR and 5'- and 3'-RACE methods, we isolated cathepsin B cDNA from
      hemocytes of Bombyx mori. The predicted open reading frame encoded 337 amino
      acids with 54% identity with the human cathepsin B, and 55% identity with the 29
      kDa proteinase of the blowfly. Three active sites characteristic for cathepsin B
      were conserved in the deduced amino acid sequences of BmCtB cDNA at positions Cys
      111, His-280 and Asn-300. Northern analysis identified a 1.3-kb mRNA. Expression
      of BmCtB was observed in the hemocytes from the day of wandering and was
      strongest at day 1 pupa. With in situ hybridization, strong signals were observed
      in the granular cells and plasmatocytes of day 0 pupa, but not in those of day 5
      of the fifth larval instar. The results indicate another function of cathepsin B
      and insect hemocyte during metamorphosis.

PMID- 11567903
TI  - Dietary mold oil rich in gamma linolenic acid increases insulin-dependent glucose
      utilization in isolated rat adipocytes.
AB  - Effects of dietary fats differing in fatty acid composition on insulin-stimulated
      glucose metabolism in adipocytes isolated from rat white adipose tissue were
      compared. Rats were fed experimental diets containing various fats differing in
      fatty acid composition for 7 days. In the first experiment, rats were fed palm
      oil mainly consisting of palmitic (45.3%) and oleic acids (39.1%) or safflower
      oil rich in linoleic acid (71.6%). In the second trial, rats were fed palm oil,
      or a fat mixture rich in linoleic acid or mold oil rich in gamma-linolenic acid.
      Contents of fatty acids except for linoleic and gamma-linolenic acid were
      comparable between the fat mixture and mold oil. The former was devoid of gamma
      linolenic acid and contained 42.0% linoleic acid, while the latter contained
      25.9% gamma-linolenic and 15.7% linoleic acids. In the first experiment, the
      insulin-dependent increase in glucose oxidation and incorporation into lipids was
      higher in rats fed safflower oil compared to those fed palm oil. In the second
      experiment, the insulin-dependent increase in glucose oxidation and incorporation
      into lipids was higher in rats fed the fat mixture and mold oil than in those fed
      palm oil. However, the extent of the increase in these parameters was much
      greater in rats fed mold oil than in those fed the fat mixture. Therefore,
      dietary gamma-linolenic acid compared to linoleic acid increases glucose
      metabolism in response to insulin stimuli in isolated rat adipocytes.

PMID- 11567904
TI  - Suppression of T(3)- and fatty acid-induced membrane permeability transition by L
      carnitine.
AB  - Cytochrome c (Cyt. c) is known to be released from the mitochondria into the
      cytosol by means of the membrane permeability transition (MPT) mechanism, thereby
      activating caspase cascade activity, and inducing cell apoptosis. Recently we
      reported that L-carnitine suppressed palmitoyl-CoA-induced MPT as well as
      apoptosis in some cell types (Biochem. Pharmacol, in press). In the present study
      T(3) was found to induce MPT and Cyt. c release, while cyclosporin A (CsA),
      bovine serum albumin (BSA) and L-carnitine were found to inhibit this action in a
      concentration-dependent manner. Similarly, long chain fatty acid (LCFA) also
      induced MPT and Cyt. c release, which was then inhibited by CsA, BSA and L
      carnitine. From these results the authors postulate that T(3)-induced MPT is in
      part regulated by fatty acid metabolism through a dynamic balance between LCFAs
      and L-carnitine.

PMID- 11567905
TI  - Effects of acclimation temperature on enzymatic capacities and mitochondrial
      membranes from the body wall of the earthworm Lumbricus terrestris.
AB  - Many ectotherms respond to low temperature by adjusting capacities of enzymes
      from energy metabolism, restructuring membrane phospholipids and modulating
      membrane fluidity. Although much is known about the temperature biology of
      earthworms, it is not known to what extent earthworms employ compensatory changes
      in enzymatic capacities and membrane physical properties after exposure to low
      temperature. We examined activities of enzymes from glycolysis and central
      oxidative pathways as well as fluidity and phospholipid fatty acid composition of
      mitochondrial membranes prepared from the body wall of the temperate oligochaete
      Lumbricus terrestris after a one month acclimation to 5 degrees and 15 degrees C.
      No compensation occurs in central pathways of oxidative metabolism since
      activities of cytochrome-c oxidase and citrate synthase, when measured at a
      common temperature, are similar for 5 degrees C and 15 degrees C-acclimated
      animals. In contrast, activity of pyruvate kinase is elevated 1.3-fold after
      acclimation to 5 degrees C. Mitochondrial membranes display inverse compensation
      with respect to temperature (membranes from 5 degrees C animals are more ordered
      than membranes from 15 degrees C animals). Our results, in combination with
      earlier reports, indicate that routine metabolism in L. terrestris may be
      maintained at reduced temperatures with little or no change in enzymatic
      capacities and inverse compensation of mitochondrial membranes.

PMID- 11567906
TI  - Interaction of N1-substituted adenines with 1-methyladenine receptors of starfish
      oocytes in induction of maturation.
AB  - Starfish oocytes are arrested naturally in the late G(2) phase of the first
      meiotic division. In response to the natural maturation-inducing hormone, 1
      methyladenine (1-MA), oocytes undergo reinitiation of meiosis with germinal
      vesicle breakdown. We tested 10 newly synthesized N1-substituted adenines that
      are 1-MA analogues to analyze the interaction between 1-MA and its stereo
      specific receptors on the oocyte plasma membranes of the starfish Asterina
      pectinifera. Among these analogues, 1-(beta-naphthylmethyl)adenine, 1
      aminoadenine and 1-(p-nitrobenzyl)adenine played agonistic roles in the induction
      of oocyte maturation. 1-(o-Nitrobenzyl)adenine, 1-(m-nitrobenzyl)adenine, 1
      phenethyladenine and 1-(p-nitrophenethyl)adenine had antagonist effects on 1-MA
      induced oocyte maturation. These agonists and antagonists behaved competitively
      in the binding of [3H]1-MA to receptors in oocyte cortices. In contrast, 1-(alpha
      naphthylmethyl)adenine, 1-(2,4-dinitrobenzyl)adenine and 1-(p
      methoxybenzyl)adenine had no effects on oocyte maturation. Our results suggest
      that regional-specific sterical structures at the N1-site of adenine are
      important in the interaction between 1-MA and its receptors in oocytes. In
      addition, a negative charge at the N1-site of adenine is required for binding
      with the receptors.

PMID- 11567907
TI  - [Oxaliplatin: perspectives and future developments].

PMID- 11567908
TI  - [Oxaliplatin: a first DACH-platinum in oncology].
AB  - Around 3,000 cisplatin analogues have been synthetised over the past 30 years but
      only half a dozen are presently in clinical development, while only two
      (cisplatin and carboplatin) have been available prior to the recent European
      registration of oxaliplatin. Oxaliplatin is a new platinum salt belonging to the
      DACH (diaminocyclohexane) platinum family, and is the only such cisplatin
      analogue that has entered clinical development and achieved approval for
      marketing. During its development, oxaliplatin has aroused lively interest due,
      firstly, to its in vitro and in vivo antitumoral activity, especially in
      cisplatin-resistant models and cell lines expressing resistance genes, and,
      secondly, to its good clinical tolerance, the absence of renal or auditory
      toxicity being combined with a low hematotoxicity. Combined with other
      antitumoral agent cytotoxic agents (5FU, raltitrexed, irinotecan or cisplatin),
      oxaliplatin produces an additive and often synergistic cytotoxic effect. The
      oxaliplatin-5FU +/- FA combination is now well established in metastatic
      colorectal cancer. Regarding its particular cytotoxic characteristics and its
      activity in mismatch repair deficient cells (which are resistant to cisplatin and
      carboplatin), oxaliplatin is shows potential in a large variety of solid tumor
      types, notably in association with other cytotoxic agents, thus opening the path
      to a wider range of indications.

PMID- 11567909
TI  - [Pharmacokinetic properties of platinium derivatives].
AB  - The three platinum derivatives currently available share many pharmacokinetic and
      pharmacodynamic (PK-PD) properties but present also some distinct
      characteristics, due to their structural differences. They result in different
      systemic PK-PD and metabolic behaviour and toxicity profile. Oxaliplatin is
      quickly transformed into dach-platinum, the active metabolite, by loosing oxalate
      chain. Eighty to eighty-eight per cent of platinum are bound to proteins, as for
      cisplatin, whereas carboplatin is less reactive. Cisplatin and oxaliplatin active
      metabolites, i.e. monoaquo platin and dach-platin quickly react with small
      proteins with sulfhydryl groups, such as glutathione, cysteine and methionine,
      and then with high molecular weight proteins, such as albumin and gammaglobulins
      through covalent link. Thus, their terminal half lives are long, about ten days,
      but no platinum accumulation has been reported in plasma with oxaliplatin,
      whereas after cisplatin administration, both total and ultrafiltrable platinum
      progressively accumulate in plasma. This difference may play a role in the lack
      of oxaliplatin nephrotoxicity and its more delayed and reversible neurotoxicity.
      On the other hand, carboplatin is more stable, less bound to proteins and is
      largely excreted inchanged in urine. This can explain that it passes more easily
      through the blood brain barrier. Erythrocytes represent an important deep
      compartment, especially for oxaliplatin, a little bit less for cisplatin.
      Oxaliplatin is trapped in erythrocytes through a covalent binding to globin.
      There, its half life is identical to that of erythrocytes. According to certain
      authors, this trapping would be involved in the incidence of anemia. On the
      contrary, carboplatin is quickly extruded from erythrocytes. The three
      derivatives kinetics in plasma present a wide interindividual variability,
      resulting in differences in term of toxicity and efficacy. For the three of them,
      plasma clearance is correlated to creatinine clearance, but only carboplatin
      dosage can be individually adjusted, based on creatinine clearance measurement,
      thanks to its simple renal excretion, due to exclusive glomerular filtration, and
      after Calvert's, Egorin's and Chatelut's population kinetics studies. Cisplatin
      renal excretion is more complex, combining reabsorption and secretion processes.
      Therefore, individual dosage adjustment needs platinum concentration measurement
      in plasma, but there is no general agreement on the platinum species to measure,
      ultrafiltrable or bound. Oxaliplatin is too recent in clinical practice and still
      lacks of PK-PD data. These characteristics can help us for a better knowledge of
      the three platinum derivatives clinical properties, both in term of kinetics,
      behaviour and toxicity.

PMID- 11567910
TI  - [Oxaliplatin in combination with 5-fluoro-uracil and folinic acid as treatment of
      metastatic colorectal cancer].
AB  - Unusual aspect of the development of oxaliplatin was that substantial evidence of
      its activity was gathered when used in combination with protracted infusion of
      5FU combined with leucovorin, preceeding the formal demonstration of its single
      activity in this disease. Phase II trials in previously treated patients by 5FU,
      have shown response rate of 10% with oxaliplatin in monotherapy and 18,4 to 58%
      with chronomodulated or bimonthly regimen combining oxaliplatin, 5FU and
      leucovorin. These trials have confirmed additive or synergistic antitumoral
      effects of this combination. Dose intensity of oxaliplatin may be important in
      determining the efficacy of the triple agent regimen. For previously untreated
      patients, Folfox4 (LV5FU2 + 85 mg/m2 of oxaliplatin) and chronomodulated regimen
      have obtained objective response rate ranged from 51 to 66%, with progression
      free survival between 8.2 and 11 months and overall survival from 16 to 19
      months. A better use of oxaliplatin in combination with 5FU and leucovorin may
      decrease the dose-limiting toxicity, i.e. the usually transient sensory
      neurotoxicity. Patients with initially unresectable metastases treated with this
      three-drug combination could sometimes underwent complete metastases surgery.
      Several studies are currently in progress either to confirm the high activity of
      the LV5FU-oxaliplatin combination or to define a strategy based on the best
      sequence or the best combinations with the other available drugs, irinotecan and
      raltitrexed.

PMID- 11567911
TI  - [Preclinical studies of oxaliplatin in combination chemotherapy].
AB  - Therapeutic innovation in oncology often requires the optimization of
      combinations with active drugs based on in vitro and in vivo data. This is
      exemplified by oxaliplatin for which several preclinical studies of combinations
      have been realized. Oxaliplatin has been combined with 5-fluoro-uracile,
      gemcitabine, topoisomerase I inhibitors, taxanes demonstrating synergy or
      additivity. Synergistic and additive effects are often due to the optimization in
      the use of distinct mechanism of action or resistance and might be associated
      with no overlapping toxicity when combined in clinical trials.

PMID- 11567912
TI  - [Oxaliplatin in combination with non fluoropyrimidine drugs in colorectal
      cancer].
AB  - After decades of exclusive use of fluorouracil in the treatment of metastatic
      colorectal cancer, three new drugs, among them oxaliplatin, have recently shown
      interesting results. Oxaliplatin has an activity when it is given alone but this
      drug is particularly interesting for combination chemotherapy because it has a
      favourable toxicity profile without important haematologic or digestive
      toxicities and because it has a convenient schedule of administration (short
      infusion every two or three weeks). Phases I and II studies have demonstrated the
      feasibility of the combination of raltitrexed and oxaliplatin. A recent phase II
      study has evaluated the efficacy of this new combination in 71 non pre-treated
      patients. The observed response rate was high: 59.5%. The combination of
      oxaliplatin and irinotecan has been assessed in three phase I studies (two with a
      three-weekly schedule and the last one with a biweekly schedule). These studies
      have determined the doses which could be used in further phase II studies, these
      doses were close to the doses used in monotherapy. Results of the efficacy of the
      three-weekly schedule are available only in second line therapy, with 42% of
      objective response rate in 36 patients. The dose intensity was maintained with
      the use of hematopoietic growth factors. These new combinations with oxaliplatin
      give us the opportunity to treat the patient with schedules excluding
      fluorouracil which has a variable metabolism.

PMID- 11567913
TI  - [Clinical use of oxaliplatin in solid tumors].
AB  - Oxaliplatin is approved in Europe for the treatment of metastatic colorectal
      cancer patients. Its antitumor activity in other solid tumors is ongoing
      evaluation and is already well established by randomized phase II studies in
      ovarian cancer. Phase II trials have also suggested a potential role for
      oxaliplatin in the treatment of non small cell lung cancers, breast cancers and
      other malignant diseases. Its large spectrum of anticancer activity is explained
      at least in part by its cytotoxicity in mismatch repair deficient cells. The
      absence of nephrotoxicity, the low hematotoxicity and the in vitro synergy with
      antimetabolites, platinums and topoisomerase I inhibitors suggest new
      chemotherapy combinations, many of them being ongoing evaluation.

PMID- 11567914
TI  - [Oxaliplatin tolerance in the treatment of metastatic colorectal cancers].
AB  - Oxaliplatin is a new platinum compound with a 1,2-diaminocyclohexane (DACH)
      carrier ligand. It has recently been developed in metastatic colorectal cancer
      treatment, where it is generally combined with 5FU and leucovorin. Safety data in
      this indication concern over 1,700 patients, who received 12,500 cycles during
      clinical trials. Oxaliplatin appears to be relatively well tolerated and easy to
      handle, even on an outpatient basis. Gastrointestinal toxicity is common, but
      controllable and rarely severe or long-lasting. Haematological and mucosal
      tolerance is satisfactory, and oxaliplatin does not seem to have renal toxicity.
      Neurological side effects are the drug's limiting toxicity and can present as
      acute neurotoxicity (dysesthesiae), which is rapidly reversible, or sometimes as
      a longer-lasting effect, correlated in this case with the cumulative dose and
      leading to functional impairment in 10 to 20% of patients after 6 cycles or more.
      Neurological symptoms improve in the vast majority of cases after treatment is
      stopped. In this situation, it is even possible to restart oxaliplatin treatment.
      Good patient information and dose adjustments should allow us to manage the
      majority of neurological toxicity associated with oxaliplatin administration.

PMID- 11567915
TI  - Health hazards in drawing and painting.
AB  - Most health hazards in drawing and painting fall into two primary categories:
      volatile organic solvents used in many painting mediums and fixatives for dry
      drawing mediums; and respirable powders and dusts such as powdered pigments and
      dyes, which may be toxic and/or suspected or known carcinogens. User safeguards,
      such as appropriate ventilation and protective attire, and protection of the
      environment through careful emission and waste disposal, can be readily
      implemented with the education of artists and their employers. This chapter
      succinctly outlines the risk factors, symptomatology, and remedies to assist
      medical professionals in providing diagnosis and treatment.

PMID- 11567916
TI  - Health hazards of printmaking.
AB  - This chapter explores hazardous exposures and health effects related to agents
      used in printmaking, such as inks, solvents, acids, and photochemicals.
      Preventive methods are also briefly addressed.

PMID- 11567917
TI  - Health hazards of ceramic artists.
AB  - Ceramic artists can be exposed to many hazards including metals (such as lead),
      fibrogenic dusts (such as silica), heat, repetitive motion, radiation, and toxic
      emissions from kilns. The health risks of these exposures have not been well
      characterized among artists, although limited information is available from
      commercial potteries. Adverse health effects may be prevented by using less
      hazardous materials (such as lead-free glazes), improved ventilation, and proper
      work practices. Special precautions must be in place if children have access to
      the ceramics studio. The use of glazed ceramic dishes can be a risk for lead
      toxicity. Food should not be stored in glazed ceramics, and pregnant women should
      avoid daily use of ceramic mugs for drinking hot beverages.

PMID- 11567918
TI  - Health hazards of photography.
AB  - Photographers are exposed to chemical, physical, and psychological hazards during
      the course of their work. Photojournalists are at physical risk from motor
      vehicle crashes and work in war zones. Ergonomic risk comes from handling heavy
      equipment as well as work in awkward postures in dangerous positions. Darkroom
      exposure to chemical agents may lead to respiratory, allergic, and nervous system
      disease. Psychological problems come from chaotic work organization. Digital
      photography may reduce the prevalence of chemical exposure, although it may
      increase the risk of musculoskeletal illness. Simple hygiene measures may prevent
      illness in photographers. An increasing number of printed resources is available
      to professional and amateur photographers; this information may help them protect
      their health while they enjoy their art.

PMID- 11567919
TI  - Health issues in journalism and reporting.
AB  - Journalists witness events and report the news. The gathering and presentation of
      this information may subject the journalist to a variety of physical and
      psychological hazards. Some health and safety risk factors are inherent within
      the profession: for example, stress associated with deadlines and reporting on
      events in dangerous climactic or social conditions. Survey data and information
      collected by professional journalism associations should be used to educate
      journalists and, whenever possible, to attenuate the risk factors. Some of the
      more common risks within the profession include those relating to travel,
      repetitive strain, and psychological stress.

PMID- 11567921
TI  - Career hazards for the dancer.
AB  - Most dance injuries are of the overuse variety. Their gradual onset, coupled with
      the intense competition for professional positions, often results in injuries
      being ignored and thus seen late in their course. While treatment of the specific
      injury is of paramount concern, maintenance of the extremes of flexibility,
      strength, and conditioning necessary to dance professionally is an equally
      important treatment element.

PMID- 11567920
TI  - Hazards in the theater.
AB  - The authors offer a survey of the myriad and unique safety and health hazards
      faced past and present by performers and theatrical workers, from preproduction
      work, through the show, and during the strike (dismantling). Special emphasis is
      given to health hazards posed by the many new plastic resin systems and adhesives
      used in set, prop, and costume construction; the hazards of special-effect fogs,
      smokes, haze, dusts, and pyrotechnic emissions; and theatrical makeup.

PMID- 11567922
TI  - Instrumental musicians' hazards.
AB  - In the last two decades, injuries to instrumental musicians have been well
      documented. Major categories of performance-related injuries include
      musculoskeletal overuse, nerve entrapment/thoracic outlet syndrome, and focal
      dystonia. Other areas of concern to instrumentalists include hypermobility,
      osteoarthritis, fibromyalgia, and hearing loss. This chapter reviews the
      epidemiology, risk factors, physical exam, treatment, and prevention of common
      problems of instrumentalists. Emphasis is placed on the team approach of
      treatment and prevention and the need for close collaboration of the various
      health professionals, music educators, and performers. Additional resources are
      presented for those interested in pursuing performing arts medicine in greater
      detail.

PMID- 11567923
TI  - Professional voice users: the evaluation of voice disorders.
AB  - Substantial advances in understanding the anatomy and physiology of phonation,
      and the new technology that has improved voice measurement and voice surgery,
      have led to marked improvement in the standard-of-care for patients with voice
      disorders. Expert voice care is essential for all patients, but especially
      crucial for voice professionals. Professional voice users include not only
      singers and actors, but also clergy, teachers, receptionists, sales personnel,
      physicians, and anyone else whose ability to earn a living is impacted negatively
      by loss of vocal quality and endurance. Physicians should be familiar with the
      latest concepts in voice diagnosis and treatment, and with the management of
      common voice disorders.

PMID- 11567924
TI  - Collections-based health hazards in museums, universities, and cultural
      institutions.
AB  - The conservation and management of objects of artistic, historic, and cultural
      significance, along with research on natural history specimens, offer a variety
      of safety and health risks both common to other professions and unique to the
      handling and study of collections. Collection objects and specimens may be
      inherently hazardous due to their natural composition or may contain residual
      pesticide and preservative chemicals acquired from decades of conservation
      practices. When assessing exposures, evaluation of risk must consider the
      intermittent nature of most work duties, the small size of the workforce, and
      overlapping duties.

PMID- 11567925
TI  - Health and safety programs for art and theater schools.
AB  - A wide variety of health and safety hazards exist in schools and colleges of art
      and theater due to a lack of formal health and safety programs and a failure to
      include health and safety concerns during planning of new facilities and
      renovation of existing facilities. This chapter discusses the elements of a
      health and safety program as well as safety-related structural and equipment
      needs that should be in the plans for any school of art or theater. These
      elements include curriculum content, ventilation, storage, housekeeping, waste
      management, fire and explosion prevention, machine and tool safety, electrical
      safety, noise, heat stress, and life safety and emergency procedures and
      equipment. Ideally, these elements should be incorporated into the plans for any
      new facilities, but ongoing programs can also benefit from a review of existing
      health and safety programs.

PMID- 11567926
TI  - Cognitive occupational hazards and psychopathology of the artist.
AB  - The author discusses creativity and mental health issues, with a focus on
      epidemiology, risk factors, and possible treatment and risk reduction. Disorders
      by type of artist are briefly addressed.

PMID- 11567930
TI  - Abstracts of the VIII European Pediatric Rheumatology Congress.

PMID- 11567931
TI  - MMR vaccine--worries are not justified.

PMID- 11567933
TI  - Case-control study of the health of those looked after by local authorities.
AB  - AIMS: To assess the health needs and provision of health care to school age
      children in local authority care. METHODS: A total of 142 children aged 5 to 16
      in local authority care, and 119 controls matched by age and sex were studied.
      Main outcome measures were routine health care, physical, emotional, and
      behavioural health, health threatening and antisocial behaviour, and health
      promotion. RESULTS: Compared with children at home, those looked after by local
      authorities were significantly more likely to: experience changes in general
      practitioner; have incomplete immunisations; receive inadequate dental care;
      suffer from anxieties and difficulties in interpersonal relationships; wet the
      bed; smoke; use illegal drugs; and have been cautioned by police or charged with
      a criminal offence. They also tend to receive less health education. They were
      significantly more likely to have had a recent hearing or eye sight test, and
      reported significantly less physical ill health overall. CONCLUSIONS: The overall
      health care of children who have been established in care for more than six
      months is significantly worse than for those living in their own homes,
      particularly with regard to emotional and behavioural health, and health
      promotion. In contrast to uncontrolled observational studies we have not found
      evidence of problems with the physical health of these children.

PMID- 11567932
TI  - Therapeutic choices in the locomotor management of the child with cerebral palsy-
      more luck than judgement?

PMID- 11567935
TI  - Should children with developmental and behavioural problems be routinely screened
      for lead?
AB  - AIM: To test the hypothesis that children with behavioural and/or developmental
      problems have significantly higher blood lead concentrations than the general
      childhood population. METHODS: Blood samples were taken from 69 children with
      behavioural and/or developmental problems and 136 controls (children admitted for
      elective day case surgery under general anaesthetic). Blood lead estimations were
      carried out using graphite furnace atomic absorption RESULTS: Children with
      behavioural and/or developmental problems had higher lead concentrations than
      controls, both in terms of their distribution across the group (mean(geometric)
      lead concentrations: 40.7 (cases), 29.2 (controls), ratio of the means(geometric)
      1.35 (95% CI 1.17, 1.58)) and the proportion of children with lead concentrations
      above those commonly defined as "toxic"-that is, 100 microg/l (12% (cases), 0.7%
      (controls); p < 0.001). Multiple linear regression suggested that this difference
      was not explained by differences in age, sex, or socioeconomic status of the two
      comparison groups. CONCLUSIONS: Children with behavioural and/or developmental
      problems are more likely to have significantly higher blood lead concentrations
      than the general childhood population. Lead, a known and more importantly, a
      treatable neurotoxin, would further contribute to the impairment suffered by
      these children. We argue that this group of children should be routinely screened
      for lead.

PMID- 11567936
TI  - How common is abuse in Greece? Studying cases with femoral fractures.
AB  - AIMS: To examine the extent of undiagnosed child abuse in Greece by studying
      young children with femoral fractures, which may be associated with abuse.
      METHODS: Fifty seven consecutive cases of children under 6 years of age with
      femoral fracture were identified from the Emergency Department Injury
      Surveillance System database. Controls were 4162 children with other orthopaedic
      injuries from the same database. RESULTS: Whereas in the literature about one
      third of femoral injuries among young children are attributed to child abuse, no
      child in the studied series had been diagnosed or even investigated in this
      context. Nevertheless, the pattern of occurrence of femoral injuries was
      compatible with that of child abuse, in that patients were frequently very young
      boys of low socioeconomic status, and the accident had frequently occurred under
      poorly identified or implausible conditions at time periods when most family
      members were crowded at home. CONCLUSIONS: Epidemiological risk factors for child
      abuse characterise femoral fractures in young children in Greece. It appears that
      child abuse is present in this country as in most other cultures. There is a
      clear need for refocusing medical personnel and hospital social services so that
      the problem is revealed, quantified, and appropriately dealt with.

PMID- 11567937
TI  - Solar disinfection of drinking water protects against cholera in children under 6
      years of age.
AB  - BACKGROUND AND AIMS: We have previously reported a reduction in risk of
      diarrhoeal disease in children who used solar disinfected drinking water. A
      cholera epidemic, occurring in an area of Kenya in which a controlled trial of
      solar disinfection and diarrhoeal disease in children aged under 6 had recently
      finished, offered an opportunity to examine the protection offered by solar
      disinfection against cholera. METHODS: In the original trial, all children aged
      under 6 in a Maasai community were randomised by household: in the solar
      disinfection arm, children drank water disinfected by leaving it on the roof in a
      clear plastic bottle, while controls drank water kept indoors. We revisited all
      households which had participated in the original trial. RESULTS: There were 131
      households in the trial area, of which 67 had been randomised to solar
      disinfection (a further 19 households had migrated as a result of severe
      drought). There was no significant difference in the risk of cholera in adults or
      in older children in households randomised to solar disinfection; however, there
      were only three cases of cholera in the 155 children aged under 6 years drinking
      solar disinfected water compared with 20 of 144 controls. CONCLUSIONS: Results
      confirm the usefulness of solar disinfection in reducing risk of water borne
      disease in children. Point of consumption solar disinfection can be done with
      minimal resources, which are readily available, and may be an important first
      line response to cholera outbreaks. Its potential in chorine resistant cholera
      merits further investigation.

PMID- 11567938
TI  - Drug misusing parents: key points for health professionals.

PMID- 11567939
TI  - Who is failing abused and neglected children?

PMID- 11567941
TI  - Fine needle aspiration biopsy of thyroid nodules.
AB  - BACKGROUND: Fine needle aspiration biopsy (FNA) is a routine diagnostic technique
      for evaluating thyroid nodules. Many reports in adults consider that FNA is
      superior to thyroid ultrasonography (USG) and radionuclide scanning (RS). Only
      five studies have been published on FNA of childhood thyroid nodules. AIMS: To
      investigate the reliability of FNA in the evaluation and management of thyroid
      nodules, and compare the results of FNA, USG, and RS with regard to final
      histopathological diagnosis. METHODS: FNA was performed in 46 children with
      thyroid nodules after USG and RS examination. We investigated the sensitivity,
      specificity, accuracy, and positive and negative predictive values of USG, RS,
      and FNA in their management. RESULTS: Six patients who had malignant or
      suspicious cells on FNA examination underwent immediate surgery. The other 40
      patients received medical treatment according to their hormonal status. Fifteen
      of these nodules either disappeared or decreased in number and/or size. Surgery
      was performed in 25 patients who did not respond to therapy. Statistical analysis
      revealed sensitivity, specificity, accuracy, and positive and negative predictive
      values respectively as follows: 60%, 59%, 59%, 15%, and 92% for USG; 30%, 42%,
      39%, 12%, and 68% for SC; 100%, 95%, 95%, 67%, and 100% for FNAB. CONCLUSION:
      FNAB is as reliable in children as in adults for definitive diagnosis of thyroid
      nodules. Using this technique avoids unnecessary thyroid surgery in children.

PMID- 11567940
TI  - Non-traumatic coma in children.

PMID- 11567942
TI  - Hypernatraemic dehydration and breast feeding: a population study.
AB  - As part of a population based regional review of all neonatal readmissions, the
      incidence of dehydration with hypernatraemia in exclusively breast fed infants
      was estimated. All readmissions to hospital in the first month of life during
      1998 from a population of 32 015 live births were reviewed. Eight of 907
      readmissions met the case definition, giving an incidence of at least 2.5 per 10
      000 live births. Serum sodium at readmission varied from 150 to 175 mmol/l. One
      infant had convulsions. The sole explanation for hypernatraemia was unsuccessful
      breast feeding in all cases. The eight cases are compared with the 65 cases
      published in the literature since 1979. Presentation, incidence, risk factors,
      pathophysiology, treatment, and prevention are discussed.

PMID- 11567943
TI  - Down's syndrome and acute lymphoblastic leukaemia: clinical features and response
      to treatment.
AB  - AIMS: To examine the clinical and biological features of acute lymphoblastic
      leukaemia in children with Down's syndrome (DS), to compare their survival with
      other children, and to determine if entry to trials and survival has improved.
      METHODS: Examination of presenting features and response to treatment in patients
      treated in two consecutive national trials, MRC UKALL X and XI. RESULTS: The
      proportion of children with DS was significantly higher in UKALL XI (1.9%) than
      UKALL X (0.9%). Children with DS tended to be under 10 years and to have the
      common ALL subtype. Cytogenetic analysis showed that favourable features, such as
      high hyperdiploidy and t(12;21) were less frequent but also that there was a lack
      of translocations associated with a poor prognosis. Children with DS showed no
      increase in risk of relapse at any site but their survival and event free
      survival were inferior to other children. These results were caused by an
      increased number of infective deaths during remission (11% compared to 2%). At
      five years overall survival was 73% in DS children compared with 82% in other
      children; event free survival was 53% compared to 63% in non-DS children.
      CONCLUSIONS: Entry of children with DS to national trials has increased and
      survival has improved. However they remain at risk of relapse and also of
      treatment related mortality. These findings emphasise the need for both intensive
      chemotherapy and optimal supportive care.

PMID- 11567944
TI  - Severe upper airway obstruction caused by ulcerative laryngitis.
AB  - AIMS: To present our experience of severe upper airway obstruction caused by
      ulcerative laryngitis in children. METHODS: Retrospective case note review of 263
      children with severe upper airway obstruction and a clinical diagnosis of croup
      admitted to a paediatric intensive care unit (PICU) over a five year period.
      RESULTS: A total of 148 children (56%) underwent microlaryngoscopy (Storz 3.0
      rigid telescope). Laryngeal ulceration with oedema was documented in 15 of these
      children (10%), median age 14 months (range 10-36) and median weight 10 kg (range
      6-12). Twenty seven of the children who underwent microlaryngoscopy (18%) also
      had ulcerative gingivostomatitis consistent with herpes simplex virus infection.
      Ulcerative laryngitis was documented in nine of 27 (33%) children with, and in
      six of 121 (5%) children without, coexistent ulcerative gingivostomatitis. One of
      the 15 children did not require airway intervention. Nine children required
      nasotracheal intubation for a median of 4 days (range 3-11) and median PICU stay
      of 6 days (range 4-14). Five children required tracheostomy ab initio, with a
      median PICU stay of 30 days (range 20-36), and duration of tracheostomy in situ
      for a median of 19 days (range 15-253). All 15 children survived. CONCLUSION:
      Ulcerative laryngitis is more common in our patient population than the few
      reports suggest. Early diagnostic microlaryngoscopy is recommended in children
      with severe croup who follow an atypical course.

PMID- 11567945
TI  - Symptomatic adrenal insufficiency during inhaled corticosteroid treatment.
AB  - Symptomatic adrenal insufficiency, presenting as hypoglycaemia or poor weight
      gain, may occur on withdrawal of corticosteroid treatment but has not previously
      been reported during inhaled corticosteroid treatment. This case series
      illustrates the occurrence of clinically significant adrenal insufficiency in
      asthmatic children while patients were on inhaled corticosteroid treatment and
      the unexpected modes of presentation. General practitioners and paediatricians
      need to be aware that this unusual but acute serious complication may occur in
      patients treated with inhaled corticosteroids.

PMID- 11567946
TI  - Peripheral gangrene during infancy: a rare presentation of systemic lupus
      erythematosus.
AB  - An 11 month old boy presented with gangrene of the extremities. He was found to
      have positive nuclear antibodies and antibodies to double stranded DNA, and
      negative Ro and La antibodies. The infant was started on oral prednisolone, which
      was discontinued after six months. At one year of follow up he was asymptomatic,
      with negative nuclear antibodies and antibodies to double stranded DNA.

PMID- 11567947
TI  - Growth study of cri du chat syndrome.
AB  - We compared the growth of children with cri du chat (5p-) syndrome with the 1990
      UK growth curves. Most subjects had impaired growth, particularly of head
      circumference. The more emaciated the child the more pronounced the microcephaly,
      showing the need for growth and nutrition monitoring.

PMID- 11567948
TI  - Successful treatment of carbohydrate deficient glycoprotein syndrome type 1b with
      oral mannose.
AB  - An Asian girl presented with failure to thrive, congenital hepatic fibrosis,
      protein losing enteropathy, and hypoglycaemia. Phosphomannose isomerase activity
      in skin fibroblasts was reduced. She is homozygous for a mutation, D131N, in the
      phosphomannose isomerase gene (PM1), consistent with the diagnosis of
      carbohydrate deficient glycoprotein syndrome type 1b. She responded to oral
      mannose treatment.

PMID- 11567949
TI  - Diagnostic and therapeutic impact of whole body positron emission tomography
      using fluorine-18-fluoro-2-deoxy-D-glucose in children with chronic granulomatous
      disease.
AB  - AIMS: To compare whole body positron emission tomography (PET) using fluorine-18
      fluoro-2-deoxy-D-glucose (FDG) with computed tomography (CT) in detecting active
      infective foci in children with chronic granulomatous disease. METHODS: We
      performed 22 whole body FDG PET studies in seven children with X linked (n = 6)
      or autosomal recessive (n = 1) CGD. All had clinical signs of infection and/or
      were evaluated prior to bone marrow transplantation (BMT). Nineteen PET studies
      were also correlated with chest and/or abdominal CT. All PET scans were
      interpreted blinded to the CT findings. Diagnoses were confirmed histologically
      and bacteriologically. RESULTS: We detected 116 lesions in 22 FGD PETs and 126
      lesions on 19 CTs. Only two of the latter could be classified reliably as active
      lesions by virtue of contrast enhancement suggesting abscess formation. PET
      excluded 59 lesions suspicious for active infection on CT and revealed 49
      infective lesions not seen on CT. All seven active infective lesions were
      identified by PET, allowing targeted biopsy and identification of the infective
      agent followed by specific antimicrobial treatment, surgery, or subsequent BMT.
      CONCLUSIONS: Identification of infective organisms is more precise if active
      lesions are biopsied. CT does not discriminate between active and inactive
      lesions. Whole body FDG PET can be used to screen for active infective lesions in
      CGD patients.

PMID- 11567950
TI  - Effect of bacterial filters on spirometry measurements.
AB  - Lung function measurements with and without a disposable bacterial filter were
      compared in 60 children. Although statistically significant, the reduction of
      lung function measurements caused by using bacterial filters was small and
      clinically irrelevant (2-4% of predicted for forced expiratory volume in one
      second and vital capacity).

PMID- 11567952
TI  - The many challenges of childhood blindness.

PMID- 11567953
TI  - Pleonasms, pomposity and plain bad English!

PMID- 11567954
TI  - Causes of severe visual impairment and blindness in children attending schools
      for the visually handicapped in the Czech Republic.
AB  - AIMS: To describe the causes of severe visual impairment and blindness in
      children in schools for the visually handicapped in the Czech Republic in 1998.
      METHODS: Pupils attending all 10 primary schools for the visually handicapped
      were examined. A modified WHO/PBL eye examination record for children with
      blindness and low vision was used. RESULTS: 229 children (146 males and 83
      females) aged 6-15 years were included in the study: 47 children had severe
      visual impairment (20.5%) (visual acuity in their better eye less than 6/60), and
      159 were blind (69.5%) (visual acuity in their better eye less than 3/60).
      Anatomically, the most affected parts of the eye were the retina (124, 54.2%),
      optic nerve (35, 15.3%), whole globe (25, 10.9%), lens (20, 8.7%), and uvea (12,
      5.2%). Aetiologically (timing of insult leading to visual loss), the major cause
      of visual impairment was retinopathy of prematurity (ROP) (96, 41.9 %), followed
      by abnormalities of unknown timing of insult (97, 42.4%), and hereditary disease
      (21, 9.2%). In 90 children (40%), additional disabilities were present: mental
      disability (36, 16%), physical handicap (16, 7%), and/or a combination of both
      (19, 8%). It was estimated that 127 children (56%) suffer from visual impairment
      caused by potentially preventable and/or treatable conditions (for example, ROP,
      cataract, glaucoma). CONCLUSIONS: Establishing a study group for comprehensive
      evaluation of causes of visual handicap in children in the Czech Republic, as
      well as for detailed analysis of present practice of screening for ROP was
      recommended.

PMID- 11567955
TI  - Prevalence of age related maculopathy in a representative Japanese population:
      the Hisayama study.
AB  - AIM: To determine the prevalence of age related maculopathy (ARM) in a
      representative older Japanese population. METHODS: 1486 residents of Hisayama
      town, Fukuoka, Japan, aged 50 years or older were examined and the presence of
      ARM was determined by grading from fundus examination by indirect ophthalmoscope,
      slit lamp, and colour fundus photographs. RESULTS: The prevalence rate of drusen,
      which occurred with comparable frequency in men and women, was 9.6%. The
      frequency of drusen increased with age (p <0.01). Hyperpigmentation and/or
      hypopigmentation of the retina was present in 3.2%, geographic atrophy in 0.2%,
      and neovascular age related macular degeneration in 0.67%. The frequency of
      neovascular age related macular degeneration was significantly higher in the men
      (1.2% v. 0.34%, p <0.01). CONCLUSIONS: Early and late stage ARM is less common
      among Japanese people than among white people in Western countries, while late
      stage ARM is more common among Japanese than among black people.

PMID- 11567956
TI  - Use of a pair of blood culture bottles for sterility testing of corneal organ
      culture media.
AB  - AIMS: To test the effectiveness and rapidity of a pair of blood culture bottles
      in the diagnosis of bacterial and fungal contamination of corneal organ culture
      media. METHODS: 761 microbiological analyses of storage media (Inosol and Exosol,
      Opsia, Toulouse, France), sampled in all phases of the organ culture at 31
      degrees C of 410 consecutive corneas, were analysed. Each medium was inoculated
      in a pair of Bactec Plus Aerobic/F and Bactec Lytic/10 Anaerobic/F blood bottles
      and placed in a Bactec 9240 incubator for 14 days at 37 degrees C and in a
      Sabouraud broth at 20 degrees C. Changes in colour or turbidity of storage media
      were evaluated daily at the corneal bank. Recipients were screened post-graft for
      infectious signs. RESULTS: Overall contamination rate was 2.4% (18/761).
      Contamination was detected in less than 1 day in 78% (14/18) and less than 2 days
      in 94% (17/18). Positivity of the microbiological controls of starting media
      preceded changes medium colour in 10 out of 14 cases. Bactec blood bottles
      allowed detection of bacteria as well as yeasts. CONCLUSION: The use of a pair of
      Bactec blood culture bottles appears reliable for the rapid diagnosis of a wide
      range of microbiological contaminations of organ cultured corneas during banking.

PMID- 11567957
TI  - The effect on intraocular pressure of latanoprost once or four times daily.
AB  - AIMS: To compare the effect on intraocular pressure (IOP) of latanoprost applied
      once daily with four times daily and to study if the difference persisted when
      treatment changed to once daily. METHODS: IOP was followed in 28 healthy
      volunteers in a double masked randomised 52 day study. Latanoprost 50 microg/ml
      was administered once daily in one eye and four times daily in the other during 2
      weeks. Subsequently both eyes received one daily drop for 2 weeks. After another
      3 weeks without treatment, a single drop was instilled in each eye. RESULTS: The
      IOP reduction on days 2 and 3 was greater in the eyes treated with four daily
      doses (p<0.01). During the following period there were no statistically
      significant differences between the eyes. After 3 weeks without treatment the IOP
      was lower than pretreatment (p<0.001). A single dose of latanoprost on day 50
      resulted in a similar decrease in IOP in both eyes. Transient photophobia, mild
      flare, and/or a few cells occurred in 15 subjects. Two subjects were withdrawn
      because of photophobia and/or signs of anterior uveitis. CONCLUSION: Latanoprost
      four times daily caused an IOP reducing effect which was similar to once daily
      dosing, except for the first 2 days of treatment when it was more effective.
      Transient photophobia, cells, and flare were common during the four dose regimen,
      but resolved spontaneously without cessation of treatment.

PMID- 11567958
TI  - Study of retinal nerve fibre layer thickness in eyes with high tension glaucoma
      and hemifield defect.
AB  - AIM: To quantitatively evaluate retinal nerve fibre layer (RNFL) difference in
      areas of apparently normal appearing visual field in eyes with high tension
      glaucoma (HTG) and hemifield defects using scanning laser polarimetry. METHODS:
      40 eyes from 40 patients with HTG with superior or inferior hemifield defects
      based on the Humphrey field analyser (HFA) underwent RNFL thickness measurements.
      20 normal eyes from 20 subjects matched in age and refractive error were selected
      as a control group. The RNFL thickness was measured with a scanning laser
      polarimeter. Mean RNFL thickness was evaluated in four quadrants (superior,
      inferior, nasal, and temporal). A superior or inferior quadrant in the defined
      ring of scanning laser polarimetry corresponds to inferior or superior hemifield
      in HFA. RESULTS: The mean RNFL thickness in the unaffected quadrant (the quadrant
      corresponding to the hemifield with apparently normal visual field based on HFA)
      of the HTG group was significantly thinner than the average RNFL thickness of the
      corresponding quadrant of the control eyes. The RNFL thickness of the unaffected
      quadrant in the eyes with HTG was reduced and statistically similar to that of
      the affected quadrant. Symmetry, calculated as the ratio of superior to inferior
      RNFL thickness, showed no statistical difference between the study and control
      group. CONCLUSION: Changes in RNFL are present in the apparently normal hemifield
      in the eyes with HTG. The thickness of the RNFL is reduced symmetrically in both
      superior and inferior quadrants based on the GDx parameters.

PMID- 11567959
TI  - Retinopathy in chronic hepatitis C patients during interferon treatment with
      ribavirin.
AB  - AIM: To assess the ocular effect of interferon alfa 2b prescribed with ribavirin
      in patients undergoing therapy for chronic hepatitis C. METHODS: 19 patients with
      chronic hepatitis C who satisfied the follow up criteria were assessed for ocular
      complications using slit lamp biomicroscopy and indirect ophthalmoscopy before,
      during, and after the treatment at regular intervals. RESULTS: 8/19 patients,
      while on treatment, developed an asymptomatic retinopathy. Among these 3/8 were
      relapsers and 5/9 were non-responders to interferon monotherapy. All retinal
      changes faded, often while the patients continued the therapy. There was no
      significant association in occurrence of retinopathy with haematological and/or
      biochemical changes. CONCLUSION: Retinopathy was more common in interferon
      monotherapy non-responders than relapsers when treated with interferon alfa 2b
      with the addition of ribavirin. The changes were transient, disappearing while
      the patients were still being treated.

PMID- 11567960
TI  - Is activated factor VII associated with retinal vein occlusion?
AB  - AIM: To determine whether a newly identified thrombophilia factor, activated
      factor VII (FVIIa), is associated with retinal vein occlusion (RVO). METHODS: 54
      consecutive cases with RVO seen between March and September 1999 were included in
      the study. 22 cases had central retinal vein occlusion (CRVO) and 32 had branch
      retinal vein occlusion (BRVO). Ophthalmoscopic examination with detailed medical
      history was followed by blood analyses for liver and renal functions,
      cholesterol, triglycerides, complete blood count, and coagulation factors
      including protein C activity, free protein S, antithrombin III, fibrinogen, and
      factor VIIa (FVIIa). Data were compared with those of the control group, composed
      of 19 cases under ophthalmological follow up for refractive errors, presbyopia,
      or senile cataract. RESULTS: Hypertension was highly prevalent in cases with
      BRVO. Complete blood count, and liver and kidney function tests were within
      normal limits in the study group. Two cases had low protein C activity, and one
      had low free protein S. FVIIa levels were significantly higher in the RVO group
      than in the control group (p=0.0004). There was no significant difference in
      FVIIa levels between the CRVO and BRVO groups (p=0.51). CONCLUSION: No
      haematological parameter except FVIIa differed significantly from that of the
      control group. Elevation of FVIIa level may play a part in the pathophysiology of
      both CRVO and BRVO.

PMID- 11567961
TI  - Non-cycloplegic screening for amblyopia via refractive findings with the Nikon
      Retinomax hand held autorefractor in 3 year old kindergarten children.
AB  - AIMS: To assess non-cycloplegic screening for amblyopia with the hand held Nikon
      Retinomax autorefractor in 3 year old kindergarten children. METHODS: 427 three
      year old children were examined in kindergarten with the Retinomax without
      cycloplegia. A gold standard was established in all children by two orthoptic
      examinations in kindergarten. If there were missing, abnormal, or inconsistent
      findings, children were referred for ophthalmological examination. If, by the
      ophthalmological examination, a new case of amblyopia requiring treatment was
      diagnosed, the gold standard was set "positive." RESULTS: In 404 children the
      gold standard was obtained. 10 children (2.5%) had a "positive" gold standard of
      unknown and untreated amblyopia. Screening sensitivity was 0.80, specificity
      0.58, accuracy 0.58, and the likelihood ratio 1.89. CONCLUSION: Non-cycloplegic
      refractive screening with the Retinomax led to many false positive referrals due
      to instrument myopia and "inconclusive" results. Hence specificity, accuracy, and
      the likelihood ratio were too low to conduct screening effectively.

PMID- 11567962
TI  - Autogenous hard palate mucosa: the ideal lower eyelid spacer?
AB  - BACKGROUND/AIMS: Raising a displaced lower eyelid frequently involves recession
      of the lower eyelid retractors with interposition of a "spacer," and several
      materials for this purpose have been described. This study reviewed the results
      of autogenous palatal mucosa in the treatment of lower eyelid displacement,
      including assessment of any donor site morbidity. METHODS: A retrospective case
      note review of consecutive patients treated at Moorfields Eye Hospital between
      1993 and 1998. All patients underwent insertion of hard palate mucosa between the
      inferior border of the tarsus and the recessed conjunctiva and lower eyelid
      retractors. Parameters studied included the underlying diagnosis, measurements of
      lower lid displacement or retraction, related previous surgery, the experience of
      the operating surgeon, intraoperative and postoperative complications, surgical
      outcome, and length of follow up. The main outcome measure was the position of
      the lower eyelid relative to the globe in primary position of gaze. RESULTS: 102
      lower eyelids of 68 patients were included and a satisfactory lid position was
      achieved in 87/102 (85%), with inadequate lengthening or significant recurrence
      of displacement occurring in 15 cases. Donor site haemorrhage requiring treatment
      in the early postoperative period occurred in seven patients (10%). CONCLUSION:
      Autogenous hard palate mucosa is an effective eyelid spacer and provides good
      long term support for the lower eyelid. Donor site complications are the main
      disadvantage, but may be minimised by attention to meticulous surgical technique
      and appropriate postoperative management.

PMID- 11567963
TI  - Autologous serum eyedrops for dry eyes and epithelial defects: clinical and in
      vitro toxicity studies.
AB  - BACKGROUND/AIMS: Autologous serum drops have been reported to be beneficial in
      keratoconjunctivitis sicca (KCS) and persistent epithelial defects (PED). A
      clinical pilot study was carried out to examine these potential uses and in vitro
      toxicity testing on corneal epithelial cell cultures was performed to compare the
      effect of serum drops with unpreserved hypromellose (hydroxypropylmethylcellulose
      0.3%). METHODS: Patients with KCS and PED, unresponsive to conventional treatment
      were recruited. Patients were examined before treatment, at 1 and 2 weeks after
      initiation, and then 2 weekly until treatment ceased. Symptoms were assessed at
      each visit. Clinical examination included Schirmer's test without anaesthesia,
      rose bengal staining, and fluorescein staining. Epithelial defects were measured
      with the slit beam. In the laboratory, cultured human corneal epithelial cells
      were exposed to serum drops and hypromellose, and their viability evaluated with
      fluorescent viability staining (Calcein AM ethidium homodimer) and an ATP assay.
      RESULTS: Autologous serum was used in 15 eyes of 13 patients with PED and 11 eyes
      of nine patients with KCS. In two patients serum drops were started after
      penetrating keratoplasty (PK). The PKs were performed for perforations secondary
      to PEDs. Of the 15 eyes with PED, nine healed at a mean of 29 days and six
      failed. The mean duration of PED before the use of serum drops was 48.2 days. Of
      the 11 eyes with KCS, six had improved subjective scores and fluorescein scores,
      and five had improved rose bengal scores after the use of serum drops. For the
      two patients who used serum eyedrops post-PK, there was a stable and intact
      epithelium at 1 week. Cessation of serum drops during the postoperative period
      led to deterioration in the subjective and objective scores in both patients. One
      developed a PED that responded to reinstitution of serum drops. The morphology
      and ATP levels of cultured epithelial cells exposed to serum were better
      maintained than those exposed to hypromellose. CONCLUSION: Autologous serum drops
      are useful for PED and KCS. This effect may be related to a number of active
      factors in serum including growth factors, fibronectin, vitamin A, and anti
      proteases. In vitro toxicity testing demonstrated that serum drops have reduced
      toxicity compared with unpreserved hypromellose. Currently regulatory
      restrictions in the UK have prevented the establishment of a prospective
      randomised controlled trial examining the efficacy of autologous serum drops for
      the management of this group of ocular surface disorders.

PMID- 11567964
TI  - Primary polypseudophakia for cataract surgery in hypermetropic eyes: refractive
      results and long term stability of the implants within the capsular bag.
AB  - AIM: To determine the long term visual and refractive results, and stability and
      complications of primary polypseudophakia using poly(methylmethacrylate) (PMMA)
      intraocular lenses (IOLs) for cataract surgery in hypermetropic eyes. METHODS:
      Prospective study of 15 short or hypermetropic eyes undergoing
      phacoemulsification with primary polypseudophakia with two PMMA IOLs implanted
      within the capsular bag. RESULTS: The spherical equivalent was reduced from a
      mean +4.87 (SD 3.00) dioptres (D) to -0.12 (1.40 D), and the deviation from the
      intended refraction was +0.005 (1.30) D, 23.6 (12.36) months post-implantation.
      The deviation from intended refraction was not statistically significant (p =
      0.989; paired t test). Postoperative best corrected visual acuity (BCVA) was 6/12
      or better in all eyes without macular or optic nerve co-morbidity.
      Interlenticular opacification (ILO) in the form of peripheral Elschnig pearls was
      seen in four (26.67%) eyes. A new type of ILO in the form of usually pigmented
      deposits in the central interface developed in five (33.33%) eyes and resulted in
      the appearance of Newton's rings in three. None of the eyes with ILO had any loss
      of BCVA or hyperopic shift. Six (40%) eyes were within 1 D from the intended
      refraction and 14 (93.33%) within 2 D. There was no statistically significant
      difference in the accuracy of the two intraocular lens calculation formulas used
      (SRK II and SRK/T). CONCLUSION: Peripheral Elschnig pearl-type ILO can occur as a
      late complication of primary in the bag implantation of two PMMA IOLs. A new type
      of ILO is described. Both types of ILO have not to date resulted in deterioration
      of visual acuity in our cohort. Use of appropriate biometry techniques and IOL
      calculation formulas may yield more accurate refractive results.

PMID- 11567965
TI  - Retinal redetachment after removal of intraocular silicone oil tamponade.
AB  - AIM: To evaluate frequency and risk factors of retinal redetachment after removal
      of intraocular silicone oil tamponade. METHODS: The study included 225 patients
      who consecutively underwent intraocular silicone oil removal at a mean interval
      of 10 months after pars plana vitrectomy had been performed by one of two
      surgeons. Mean follow up time was 17.37 (SD 14.40) months (range 3.02-67.42
      months). RESULTS: In 57 of 225 (25.3%) patients, the retina detached after
      removal of silicone oil. Risk factors for retinal redetachment were the
      following: number of previously unsuccessful retinal detachment surgeries
      (p=0.0008); surgeon (p=0.007); visual acuity before silicone oil removal
      (p=0.009); incomplete removal of vitreous base (p=0.01); absence of an encircling
      band in eyes with proliferate vitreoretinopathy in which an inferior retinotomy
      had not been performed (p=0.01); and indication for pars plana vitrectomy. Rate
      of retinal redetachment was statistically (p>0.05) independent of the technique
      of silicone oil removal and duration of silicone oil endotamponade. CONCLUSION:
      Retinal redetachment after removal of silicone oil endotamponade can occur in
      approximately a fourth of patients, depending on the criteria to use and to
      remove silicone oil. Risk factors for recurrent detachment included the
      following: number of previously unsuccessful retinal detachment surgeries,
      surgeon, preoperative visual acuity, incomplete removal of the vitreous base,
      absence of an encircling band, and reason for pars plana vitrectomy. The rate of
      retinal redetachment is independent of the technique of silicone oil removal and
      duration of silicone oil endotamponade, with a minimal duration of silicone oil
      tamponade of about 3 months in the present study.

PMID- 11567966
TI  - Cell proliferation activity in posterior uveal melanoma after Ru-106
      brachytherapy: an EORTC ocular oncology group study.
AB  - AIM: To evaluate the cell proliferation activity in posterior uveal melanomas
      after Ru-106 brachytherapy. METHODS: Eyes containing choroidal or ciliary body
      melanoma from seven ocular oncology centres, which were enucleated after first
      being treated by Ru-106 brachytherapy and which had enough melanoma tissue to
      enable histological assessment, were included. The 57 eligible specimens were
      divided into a group of 44 eyes that were enucleated because of tumour regrowth,
      and a non-recurrent group of 13 eyes that were enucleated because of
      complications such as neovascular glaucoma. 46 non-irradiated eyes harbouring
      uveal melanoma served as a control group. All specimens underwent routine
      processing. They were cut into 5 microm sections, and were stained with two main
      cell proliferation markers: PC-10 for PCNA and MIB-1 for Ki-67. The stained
      sections were assessed, and the cells that were positive in the immunostaining
      were counted in each section. The results were evaluated by various statistical
      methods. RESULTS: The PC-10 score showed a statistically significant difference
      across the three groups (p = 0.002). The control group showed the highest PC-10
      score (median 31.0 PCC/HPF) followed by the tumour regrowth group (median 4.9
      PCC/HPF). The lowest PC-10 scores were found in the non-recurrent tumours (median
      0.05 PCC/HPF). The MIB-1 score in the control group (median 5.77 PCC/HPF) was
      similar to the regrowth group (median 5.4 PCC/HPF). In contrast, the MIB-1 score
      in the non-recurrent tumours was statistically significantly lower (median 0.42
      PCC/HPF). The PC-10 and MIB-1 scores were similar in tumours composed of either
      spindle cells or epithelioid cells in all groups. CONCLUSIONS: The non-recurrent
      melanomas demonstrate significantly lower cellular proliferation activity than
      melanomas that showed regrowth or that were not irradiated at all. In our hands,
      PCNA gave more meaningful information than Ki-67. Our findings strongly support
      the need for treating regrowing posterior uveal melanoma either by enucleation or
      re-treatment by brachytherapy. On the other hand, also in the non-recurrent uveal
      melanomas there are viable cells with potential for proliferation, although fewer
      in number, with unknown capacity for metastatic spread. Therefore, the irradiated
      tumours should be followed for many years, probably for life.

PMID- 11567967
TI  - Uveal tumour resection.
AB  - AIM: To review the ocular retention rates, visual results, and metastases in
      uveal tumours managed with eye wall resection techniques. METHODS: This was a
      retrospective analysis of consecutive local uveal tumour resections performed by
      a single surgeon. All enucleation specimens were reviewed by one author. Both
      parametric and non-parametric analysis of data were performed. RESULTS: 138 eyes
      were scheduled for eye wall resection surgery. The mean age was 52 years (range
      11-86 years). Tumours involved predominantly the iris in 14 cases, iris-ciliary
      body in 57, ciliary body alone in 18 patients, and in 49 cases the choroid was
      involved (ciliochoroidal, iris-ciliary body-choroid, or choroid). 125 eyes
      harboured melanomas; posterior tumours were more likely to have epithelioid cells
      (p<0.05). The mean follow up was 6 years. The mean clock hours in iris and iris
      ciliary body tumours was 3.5. In tumours that involved the choroid the mean
      largest diameter was 12.9 mm and the mean thickness 8.5 mm. 105 of 138 (76%) eyes
      were retained. Histological assessment of surgical margins did not correlate
      evidence of tumour in enucleated eyes or metastatic disease. Surgical margins of
      more anterior tumours were more likely to be clear on histological evaluation
      (p<0.05). Approximately 53% of retained eyes had a final visual acuity of > or
      =20/40; visual results were significantly better in more anteriorly located
      tumours (p<0.05). All retained iris tumour cases had > or =20/40 final visual
      acuity. In tumours that involved the choroid nine of 31 retained eyes kept that
      level of visual acuity. Eight patients developed metastases; all metastatic
      events developed in patients with tumours that involved the choroid, and seven of
      eight were mixed cell melanomas. CONCLUSIONS: 76% of eyes were retained and 53%
      of these had a final visual acuity of > or =20/40. Only 7% of uveal melanoma
      patients developed metastatic disease with a mean follow up of 6 years. Survival
      did not appear to be compromised with eye wall resection and in very thick, more
      posterior melanomas it appeared that ocular retention and visual results were
      better than with radiation alone.

PMID- 11567968
TI  - A role for methotrexate in the management of non-infectious orbital inflammatory
      disease.
AB  - AIM: To evaluate the clinical usefulness of methotrexate for patients with non
      infectious orbital inflammatory disease who fail to respond to systemic
      corticosteroids and/or orbital irradiation. METHODS: The medical records of
      patients with non-infectious orbital inflammatory disease who were treated with
      methotrexate at Oregon Health Sciences University between June 1993 and June 2000
      were examined. Methotrexate was administered at a median maximum dose of 20 mg
      per week (range 15-25 mg per week) in conjunction with folate supplementation.
      Patients were followed with regular ophthalmic examinations, as well as serum
      liver enzyme levels and blood cell counts. Clinical signs of regression of the
      orbital inflammation, visual acuity, dosage and duration of methotrexate therapy,
      requirement for concurrent corticosteroid administration, and adverse drug
      reactions were recorded. RESULTS: The study cohort included 14 patients (24 eyes)
      with diagnoses including non-specific orbital inflammation (n=7), Tolosa-Hunt
      syndrome (n=1), thyroid orbitopathy (n=3), Wegener's granulomatosis (n=1),
      sarcoidosis (n=1), and Erdheim-Chester disease (n=1). In all cases, methotrexate
      was commenced as a corticosteroid sparing agent. 10 patients (71%) completed a 4
      month therapeutic trial of methotrexate. Median duration of treatment for the
      nine (64%) patients who experienced clinical benefit was 25 months (range 10-47
      months). Six responders were ultimately able to cease methotrexate, including the
      single patient who required concurrent long term corticosteroid therapy.
      Complications included fatigue, gastrointestinal disturbance, hair thinning and
      mild, reversible serum liver enzyme elevation. Two patients (14%) discontinued
      treatment because of adverse effects. CONCLUSION: Methotrexate is a well
      tolerated immunosuppressive medication which may benefit patients with
      recalcitrant non-infectious orbital inflammatory disease.

PMID- 11567969
TI  - Pupillary autonomic denervation with increasing duration of diabetes mellitus.
AB  - BACKGROUND/AIMS: The autonomic pupillary changes in type I and II diabetic
      patients without clinical evidence of diabetic autonomic neuropathy (DAN) were
      compared with age matched controls. The relation between pupillary and
      cardiovascular autonomic function was assessed in the diabetic patients. METHODS:
      A case-control study was performed with diabetics grouped according to type and
      duration of diabetes. Static infrared pupillography was used to compare mean dark
      adapted pupil size and mean percentage changes in pupil size with pilocarpine
      0.1% and cocaine 4% in the diabetic and control groups. All diabetic patients
      underwent cardiovascular autonomic function assessment using the Valsalva ratio,
      the 30:15 ratio, and testing for orthostatic hypotension. RESULTS: In total, 72
      type I and 69 type II diabetic patients were compared with 120 controls. Mean
      dark adapted pupil size was significantly smaller in diabetic groups than
      controls. Except for type I diabetics with disease for less than 5 years, all
      patient groups had significantly greater mean percentage constriction in pupil
      size in response to dilute pilocarpine than controls. There was no significant
      difference between the mean percentage dilatation in response to cocaine 4% in
      diabetics and controls. A high proportion of patients had normal cardiovascular
      autonomic function particularly when this was assessed with the Valsalva ratio.
      CONCLUSIONS: Denervation hypersensitivity to dilute pilocarpine is a result of
      damage to the pupillary parasympathetic supply of diabetic patients. This occurs
      before the pupillary sympathetic pathway is affected, it can be detected early in
      the disease, and it may be a possible explanation for the small pupil size seen
      in diabetic patients. Pupillary autonomic dysfunction occurs before
      cardiovascular autonomic changes and detection of pupil denervation
      hypersensitivity to dilute pilocarpine is an inexpensive way to detect early DAN.

PMID- 11567970
TI  - Experimental flow studies in glaucoma drainage device development.
AB  - AIMS: (I) To examine whether small holes produced by 248 nm excimer laser
      ablation in a polymer substrate could consistently produce a pressure drop in the
      desired target range (5-15 mm Hg) at physiological aqueous flow rates for use as
      an internal flow restrictor in a glaucoma drainage device, and (ii) to
      investigate whether external leakage could be reduced in comparison with
      conventional tube and plate glaucoma drainage devices by redesigning the exterior
      cross sectional shape of the portion contained within the sclerocorneal tunnel.
      METHODS: Single holes with target diameters of 10 microm, 15 microm, 20 microm,
      and 25 microm were drilled using a 248 nm excimer laser in sample discs (n=6 at
      each diameter) punched from a 75 microm thick polyimide sheet. Sample discs were
      tested in a flow rig designed to measure the pressure drop across the discs.
      Using filtered, degassed water at a flow rate of 1.4 microl/min repeated flow
      measurements were taken (n=6) for each disc. After flow testing, all discs were
      imaged using a scanning electron microscope and the dimensions of each hole were
      derived using image analysis software. In the external leakage study,
      corneoscleral buttons (n=13) were prepared from cadaver pig eyes and mounted on
      an artificial anterior chamber infused with Tyrode solution. After the pressure
      had stabilised, standard occluded silicone tube implants were inserted through 23
      gauge needle stab incisions at the limbus. These were compared against prototype
      PMMA implants with a novel shape profile inserted through 1.15 mm width
      microvitreoretinal (MVR) stab incisions at the limbus. The infusion rate was
      maintained and a second pressure measurement was taken when the pressure had
      stabilised. The difference between the first and second pressure measurement was
      then compared, as an index of external leakage. RESULTS: Ablated tubes were found
      to have a near perfect circular outline on both the entry and exit side. The
      observed pressure drops across the ablated sample discs at each target diameter
      were as follows: 10 microm, mean 25.66 (SD 4.9) mm Hg; 15 microm, 6.7 (1.15); 20
      microm, 1.66 (1.07); and 25 microm, <0.1 mm Hg. A strong correlation was observed
      between observed pressure drops and those predicted by Poiseuille's formula (R(2)
      =0.996). Target ablations of 15 microm diameter produced tubes that consistently
      achieved a pressure drop within the desired range (5-15 mm Hg). In the external
      leakage study, preinsertion pressures (mm Hg; mean (SD)) were 19.00 (4.3)
      (conventional method) and 20.00 (3.9) (new technique with PMMA prototypes). Post
      insertion pressures were significantly reduced (10.40 (7.7); p<0.01) for the
      conventional technique and were essentially unchanged for the new technique
      (18.80 (4.9); p>0.1). CONCLUSIONS: It was shown that it is possible, in
      principle, to control the dimensions of a manufactured tubular lumen in a
      glaucoma drainage device accurately enough to provide consistent protection from
      hypotony in the early period after glaucoma filtration surgery. By redesigning
      the external profile of glaucoma drainage device and incision technique, it was
      also shown that it is possible to eliminate uncontrolled external leakage.

PMID- 11567972
TI  - Interphase fluorescence in situ hybridisation of the X and Y chromosomes in the
      human eye.
AB  - AIM: To determine the sex of individual cells in paraffin sections of the human
      eye by fluorescence in situ hybridisation (FISH) of the X and Y chromosomes.
      METHODS: The authors developed a protocol for FISH of the X and Y chromosomes in
      paraffin sections of human eyes. RESULTS: In all the specimens that had been
      fixed in 10% formalin and with a fixation time of up to 3 days sex determination
      of individual cells was achieved. The percentage of cells with clearly
      identifiable signals was up to 98% for corneal epithelium, keratocytes, corneal
      endothelium, trabecular meshwork, lens epithelium, retina, and optic nerve.
      CONCLUSIONS: FISH allows the determination of the sex of single cells in paraffin
      sections of human eyes without destruction of the tissue structure. Its main
      application is the histological analysis of sex mismatched corneal, RPE, or
      neuroretinal transplants to distinguish host and donor cells.

PMID- 11567971
TI  - Light induced apoptosis is accelerated in transgenic retina overexpressing human
      EAT/mcl-1, an anti-apoptotic bcl-2 related gene.
AB  - BACKGROUND/AIM: EAT/mcl-1 (EAT), an immediate early gene, functions in a similar
      way to bcl-2 in neutralising Bax mediated cytotoxicity, suggesting that EAT is a
      blocker of cell death. The aim of this study was to determine the effect of
      overexpression of the human EAT gene on light induced retinal cell apoptosis.
      METHODS: EAT transgenic mice incorporating the EF-1alpha promoter were utilised,
      and expression of human EAT was detected by RT-PCR. Light damage was induced by
      raising mice under constant illumination. Two groups of animals, EAT transgenic
      mice (n=14) and littermates (n=13), were examined by ERG testing and
      histopathology at regular time points up to 20 weeks of constant light
      stimulation. Electrophysiological and histopathological findings were evaluated
      by established systems of arbitrary scoring as scores 0-2 and scores 0-3,
      respectively. RESULTS: The mean score (SD) of ERG response was significantly
      lower in EAT transgenic mice (0.79 (0.89)) than in littermates (1.69 (0.48))
      (p<0.01). Although the differences between the two survival curves did not reach
      statistical significance (p=0.1156), the estimated incidence of
      electrophysiological retinal damage was higher in EAT mice (0.0495/mouse/week;
      95% confidence interval (CI) 0.0347-0.0500) than in littermates (0.
      0199/mouse/week; 95% CI 0.0035-0.0364). The mean scores (SD) for
      histopathological retinal degeneration were 2.31 (0.63) in littermates and 1.43
      (1.22) in EAT transgenic mice (p=0.065). However, Kaplan-Meier curves for
      histopathological failure in two groups of mice showed that retinal photoreceptor
      cells were preserved significantly against constant light in the littermate
      compared with transgenic mice (p=0.0241). The estimated incidence of
      histopathological retinal damage was 0.0042/mouse/week in the littermates (95% CI
      0-0.0120) and 0.0419/mouse/week in the EAT mice (95% CI 0.0286-0.0500).
      CONCLUSION: Retinal photoreceptor cell apoptosis under constant light stimulation
      is likely to be accelerated in transgenic retina overexpressing EAT.

PMID- 11567973
TI  - Temporal artery biopsy in the management of giant cell arteritis with neuro
      ophthalmic complications.

PMID- 11567975
TI  - TTT and CNV.

PMID- 11567981
TI  - Removing the cloud from industry-sponsored, multicentered clinical trials.

PMID- 11567974
TI  - A hypothesis to explain ganglion cell death caused by vascular insults at the
      optic nerve head: possible implication for the treatment of glaucoma.

PMID- 11567982
TI  - Systemic therapy of myeloma xenografts by an attenuated measles virus.
AB  - Conditionally replicating viruses are promising agents for the treatment of
      malignancy. Here it is shown that the live attenuated Edmonston-B vaccine strain
      of measles virus (MV-Edm) replicates selectively in human myeloma cells and has
      potent antitumor activity. In vitro, replication of MV-Edm was restricted in
      phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PBLs) but
      proceeded efficiently in a panel of 6 myeloma cell lines-ARH-77, RPMI 8226, JJN
      3, MM1, KAS-6/1, and KMS-11-and in primary myeloma cells isolated by CD138
      sorting from the bone marrow aspirates of 6 patients. MV-Edm infection induced
      potent cytopathic effects in these myeloma cells, resulting in the formation of
      multinucleated syncytia that eventually became nonviable. In contrast, syncytial
      formation in PHA-stimulated PBLs was minimal after MV-Edm infection. In vivo, MV
      Edm was antitumorigenic and inhibited the establishment of myeloma cells as
      xenografts in immunocompromised mice. When injected directly into ARH-77 myeloma
      xenografts in the mice, MV-Edm caused complete regression of these xenografts. MV
      Edm administered intravenously into the tail veins of mice also showed
      significant antineoplastic activity against established RPMI 8226 and ARH-77
      xenografts. In particular, the ARH-77 myeloma xenografts were exquisitely
      sensitive to MV-Edm therapy, and tumors in all mice regressed completely. In
      light of its selectivity for myeloma cells and its potent antineoplastic activity
      against myeloma xenografts in vivo, MV-Edm merits further development for the
      treatment of multiple myeloma.

PMID- 11567983
TI  - Bone marrow origin of hematopoietic progenitors and stem cells in murine muscle.
AB  - It has been reported that mononuclear cells harvested from murine skeletal muscle
      are capable of hematopoietic reconstitution of lethally irradiated mice. First,
      the nature of the hematopoietic progenitors in the muscle of C57BL/6-Ly-5.1 mice
      was examined by means of methylcellulose culture. The types and incidences of
      colonies grown from muscle mononuclear cells were different from those cultured
      from bone marrow (BM) or peripheral blood mononuclear cells. The next step was to
      examine the origin of the hematopoietic progenitors and stem cells in the muscle
      with the use of Ly-5.2 mice that had been made chimeric by transplantation of Ly
      5.1 BM cells. The percentages of Ly-5.1 cells cultured from the muscle of the
      chimeric mice correlated with those cultured from BM, indicating BM origin of
      hematopoietic progenitors in the muscle. Long-term hematopoietic engrafting cells
      in the muscle of the chimeric mice were also derived from BM. However,
      mobilization of progenitors into circulation by granulocyte colony-stimulating
      factor did not change the population of hematopoietic progenitors in the muscle.
      It is proposed that hematopoietic progenitors and stem cells in the muscle tissue
      are of BM origin but their transition from BM to muscle may be a slow process.

PMID- 11567984
TI  - Transduction of a dominant-negative H-Ras into human eosinophils attenuates
      extracellular signal-regulated kinase activation and interleukin-5-mediated cell
      viability.
AB  - Inhibition of eosinophil apoptosis by exposure to interleukin-5 (IL-5) is
      associated with the development of tissue eosinophilia and may contribute to the
      inflammation characteristic of asthma. Analysis of the signaling events
      associated with this process has been hampered by the inability to efficiently
      manipulate eosinophils by the introduction of active or inhibitory effector
      molecules. Evidence is provided, using a dominant-negative N17 H-Ras protein (dn
      H-Ras) and MEK inhibitor U0126, that activation of the Ras-Raf-MEK-ERK pathway
      plays a determining role in the prolongation of eosinophil survival by IL-5. For
      these studies, a small region of the human immunodeficiency virus Tat protein, a
      protein transduction domain known to enter mammalian cells efficiently, was fused
      to the N-terminus of dn-H-Ras. The Tat-dn-H-Ras protein generated from this
      construct transduced isolated human blood eosinophils at more than 95%
      efficiency. When Tat-dn-H-Ras-transduced eosinophils were treated with IL-5, they
      exhibited a time- and dosage-dependent reduction in extracellular regulated
      kinase 1 and 2 activation and an inhibition of p90 Rsk1 phosphorylation and IL-5
      mediated eosinophil survival in vitro. In contrast, Tat-dn-H-Ras did not inhibit
      CD11b up-regulation or STAT5 tyrosine phosphorylation. These data demonstrate
      that Tat dominant-negative protein transduction can serve as an important and
      novel tool in studying primary myeloid cell signal transduction in primary
      leukocytes and can implicate the Ras-Raf-MEK-ERK pathway in IL-5-initiated
      eosinophil survival.

PMID- 11567985
TI  - Targeted deletion of 5'HS1 and 5'HS4 of the beta-globin locus control region
      reveals additive activity of the DNaseI hypersensitive sites.
AB  - The mammalian beta-globin locus is a multigenic, developmentally regulated,
      tissue-specific locus from which gene expression is regulated by a distal
      regulatory region, the locus control region (LCR). The functional mechanism by
      which the beta-globin LCR stimulates transcription of the linked beta-like globin
      genes remains unknown. The LCR is composed of a series of 5 DNaseI hypersensitive
      sites (5'HSs) that form in the nucleus of erythroid precursors. These HSs are
      conserved among mammals, bind transcription factors that also bind to other parts
      of the locus, and compose the functional components of the LCR. To test the
      hypothesis that individual HSs have unique properties, homologous recombination
      was used to construct 5 lines of mice with individual deletions of each of the
      5'HSs of the endogenous murine beta-globin LCR. Here it is reported that deletion
      of 5'HS1 reduces expression of the linked genes by up to 24%, while deletion of
      5'HS4 leads to reductions of up to 27%. These deletions do not perturb the normal
      stage-specific expression of genes from this multigenic locus. In conjunction
      with previous studies of deletions of the other HSs and studies of deletion of
      the entire LCR, it is concluded that (1) none of the 5'HSs is essential for
      nearly normal expression; (2) none of the HSs is required for proper
      developmental expression; and (3) the HSs do not appear to synergize either
      structurally or functionally, but rather form independently and appear to
      contribute additively to the overall expression from the locus.

PMID- 11567986
TI  - Embryonic and hematopoietic stem cells express a novel SH2-containing inositol 5'
      phosphatase isoform that partners with the Grb2 adapter protein.
AB  - SH2-containing inositol 5'-phosphatase (SHIP) modulates the activation of immune
      cells after recruitment to the membrane by Shc and the cytoplasmic tails of
      receptors. A novel SHIP isoform of approximately 104 kd expressed in primitive
      stem cell populations (s-SHIP) is described. It was found that s-SHIP is
      expressed in totipotent embryonic stem cells to the exclusion of the 145-kd SHIP
      isoform expressed in differentiated hematopoietic cells. s-SHIP is also expressed
      in primitive hematopoietic stem cells, but not in lineage-committed hematopoietic
      cells. In embryonic stem cells, s-SHIP partners with the adapter protein Grb2
      without tyrosine phosphorylation and is present constitutively at the cell
      membrane. It is postulated that s-SHIP modulates the activation threshold of
      primitive stem cell populations.

PMID- 11567987
TI  - Chronic myeloid leukemia: current treatment options.
AB  - The choice of primary treatment for patients with chronic myeloid leukemia (CML)
      diagnosed in chronic phase has become exceedingly difficult. There is little
      doubt that allogeneic stem cell transplantation can eradicate the leukemia and
      that a graft-versus-leukemia effect makes a major contribution to this result;
      conversely, only a minority of patients are eligible for transplantation, which
      still carries an appreciable risk for death or protracted illness. For most
      patients, interferon-alpha (IFN-alpha) prolongs life to some degree in comparison
      with hydroxyurea, but it is associated with considerable toxicity. The newly
      introduced tyrosine kinase inhibitor STI571 induces complete hematologic
      remission in almost all patients and is associated with a very high rate of
      cytogenetic response; its capacity to prolong life in comparison with IFN-alpha
      is not yet established. Here are reviewed some factors that predict survival
      after nontransplantation therapy and after allografting for CML in chronic phase.
      Two contrasting options are considered for managing the patient with newly
      diagnosed disease, and it can be concluded that, for now, allogeneic stem cell
      transplantation soon after diagnosis should continue to be offered as an option
      for selected patients. Further experience with the use of STI571 as a single
      agent or in combination with other antileukemic agents may alter the picture in
      the near future.

PMID- 11567988
TI  - Donor characteristics as risk factors in recipients after transplantation of bone
      marrow from unrelated donors: the effect of donor age.
AB  - The National Marrow Donor Program (NMDP) maintains a registry of approximately 4
      million volunteer unrelated donors for patients in need of a stem cell
      transplant. When several comparably HLA-matched volunteers are identified for a
      patient, various criteria are used to select a donor. A retrospective analysis of
      6978 bone marrow transplantations facilitated by the NMDP from 1987 to 1999 was
      conducted to study the effects of various donor characteristics on recipient
      outcome. The evaluation addressed possible effects of donor age, cytomegalovirus
      serologic status, ABO compatibility, race, sex, and parity on overall and disease
      free survival, acute and chronic graft-versus-host disease (GVHD), engraftment,
      and relapse. Age was the only donor trait significantly associated with overall
      and disease-free survival. Five-year overall survival rates for recipients were
      33%, 29%, and 25%, respectively, with donors aged 18 to 30 years, 31 to 45 years,
      and more than 45 years (P =.0002). A similar effect was observed among HLA
      mismatched cases (28%, 22%, and 19%, respectively). A race mismatch between
      recipient and donor did not affect outcome. The cumulative incidences of grade
      III or IV acute GVHD were 30%, 34%, and 34%, respectively, with donors aged 18 to
      30 years, 31 to 45 years, and more than 45 years (P =.005). The corresponding
      incidences of chronic GVHD at 2 years were 44%, 48%, and 49% (P = 0.02).
      Recipients with female donors who had undergone multiple pregnancies had a higher
      rate of chronic GVHD than recipients with male donors (54% versus 44%; P <.0001).
      The use of younger donors may lower the incidence of GVHD and improve survival
      after bone marrow transplantation. Age should be considered when selecting among
      comparably HLA-matched volunteer donors.

PMID- 11567989
TI  - Treatment of steroid-refractory acute graft-versus-host disease with anti-CD147
      monoclonal antibody ABX-CBL.
AB  - ABX-CBL, an immunoglobulin M murine monoclonal antibody, recognizes CD147 and
      initiates cell killing through complement-mediated lysis. In a dose-finding
      trial, 27 patients with steroid-refractory acute graft-versus-host disease (GVHD)
      received ABX-CBL at 0.01 (presumed no effect dose), 0.1, 0.2, or 0.3 mg/kg per
      day, and an additional 32 patients were given ABX-CBL at 0.2 or 0.15 mg/kg per
      day. All patients had undergone allogeneic transplantation for malignant or
      nonmalignant disorders and received GVHD prophylaxis, generally with methotrexate
      and cyclosporine-containing regimens. None responded to methylprednisolone,
      given for a minimum of 3 days. ABX-CBL was started 20 to 236 (median, 47) days
      after transplantation; it was given for 7 consecutive days and was followed by 2
      infusions per week for 2 more weeks. Among 51 patients evaluable for efficacy, 26
      (51%) responded, including 13 with complete responses (CR) and 13 with partial
      responses (PR). CR lasting 14 days or longer or PR lasting 7 days or longer
      occurred in 21 (41%; 8 CR, 13 PR) patients, including 19 of 43 (44%) patients who
      received 0.1 to 0.3 mg/kg ABX-CBL and 2 of 8 (25%) patients given 0.01 mg/kg per
      day. Myalgias at doses 0.2 mg/kg or greater were dose limiting and resolved
      without sequelae. Causes of death included organ failure, progressive GVHD, and
      infection. No death was attributed to ABX-CBL. At 6 months after the initiation
      of ABX-CBL therapy, 26 (44%) patients were surviving. These results are
      encouraging. Further studies on the use of ABX-CBL in the management of GVHD are
      warranted.

PMID- 11567990
TI  - Randomized trial of filgrastim versus chemotherapy and filgrastim mobilization of
      hematopoietic progenitor cells for rescue in autologous transplantation.
AB  - Peripheral blood cell (PBC) rescue has become the mainstay for autologous
      transplantation in patients with lymphoma, multiple myeloma, and solid tumors.
      Different methods of hematopoietic progenitor cell (HPC) mobilization are in use
      without an established standard. Forty-seven patients with relapsed or refractory
      lymphoma received salvage chemotherapy and were randomized to have HPC
      mobilization using filgrastim [granulocyte-colony-stimulating factor (G-CSF)]
      alone for 4 days at 10 microg/kg per day (arm A) or cyclophosphamide (5 g/m(2))
      and G-CSF at 10 microg/kg per day until hematologic recovery (arm B). Engraftment
      and ease of PBC collection were primary outcomes. All patients underwent the same
      high-dose chemotherapy followed by reinfusion of PBCs. There were no differences
      in median time to neutrophil engraftment (11 days in both arms; P =.5) or
      platelet engraftment (14 days in arm A, 13 days in arm B; P =.35). Combined
      chemotherapy and G-CSF resulted in higher CD34(+) cell collection than G-CSF
      alone (median, 7.2 vs 2.5 x 10(6) cells/kg; P =.004), but this did not impact
      engraftment. No differences were found in other PBC harvest outcomes or resource
      utilization measures. A high degree of tumor contamination, as studied by
      consensus CDR3 polymerase chain reaction of the mobilized PBCs, was present in
      both arms (92% in arm A vs 90% in arm B; P = 1). No differences were found in
      overall survival or progression-free survival at a median follow-up of 21 months.
      This randomized trial provides clinical evidence that the use of G-CSF alone is
      adequate for HPC mobilization, even in heavily pretreated patients with relapsed
      lymphoma.

PMID- 11567991
TI  - Sustained multilineage gene persistence and expression in dogs transplanted with
      CD34(+) marrow cells transduced by RD114-pseudotype oncoretrovirus vectors.
AB  - Previous studies have shown that the choice of envelope protein (pseudotype) can
      have a significant effect on the efficiency of retroviral gene transfer into
      hematopoietic stem cells. This study used a competitive repopulation assay in the
      dog model to evaluate oncoretroviral vectors carrying the envelope protein of the
      endogenous feline virus, RD114. CD34-enriched marrow cells were divided into
      equal aliquots and transduced with vectors produced by the RD114-pseudotype
      packaging cells FLYRD (LgGLSN and LNX) or by the gibbon ape leukemia virus (GALV)
      pseudotype packaging cells PG13 (LNY). A total of 5 dogs were studied. One dog
      died because of infection before sustained engraftment could be achieved, and
      monitoring was discontinued after 9 months in another animal that had very low
      overall gene-marking levels. The 3 remaining animals are alive with follow-ups at
      11, 22, and 23 months. Analyses of gene marking frequencies in peripheral blood
      and marrow by polymerase chain reaction revealed no significant differences
      between the RD114 and GALV-pseudotype vectors. The LgGLSN vector also contained
      the enhanced green fluorescent protein (GFP), enabling us to monitor proviral
      expression by flow cytometry. Up to 10% of peripheral blood cells expressed GFP
      shortly after transplantation and approximately 6% after the longest follow-up of
      23 months. Flow cytometric analysis of hematopoietic subpopulations showed that
      most of the GFP-expressing cells were granulocytes, although GFP-positive
      lymphocytes and monocytes were also detected. In summary, these results show that
      RD114-pseudotype oncoretroviral vectors are able to transduce hematopoietic long
      term repopulating cells and, thus, may be useful for human stem cell gene
      therapy.

PMID- 11567992
TI  - Suicide gene therapy of graft-versus-host disease: immune reconstitution with
      transplanted mature T cells.
AB  - After allogeneic hematopoietic stem cell transplantation (HSCT), mature
      transplanted T cells play a major role in restoration of the immune system.
      However, they can also induce a life-threatening complication: graft-versus-host
      disease (GVHD). Suicide gene therapy of GVHD aims to selectively eliminate
      alloreactive T cells mediating GVHD while sparing nonalloreactive T cells that
      should contribute to immune reconstitution. It was demonstrated previously that
      treatment with ganciclovir (GCV) can control GVHD in mice by killing donor T
      cells engineered to express the thymidine kinase (TK) suicide gene. TK allows
      phosphorylation of nontoxic GCV into triphosphate GCV, which is selectively toxic
      for dividing cells. Thus, in the TK-GCV system, the specificity of cell killing
      depends on the cycling status of TK T cells rather than allogeneic recognition.
      This is a potential drawback because in recipients of lymphopenic allogeneic
      HSCT, alloreactive and homeostatic signals drive the proliferation of donor T
      cells. It is shown here that the onset of alloreactive T-cell division occurs
      earlier than that of nonalloreactive T cells, thus establishing a time frame for
      GCV administration. A 7-day GCV treatment initiated at the time of HSCT allowed
      efficient prevention of GVHD, while sparing a pool of nondividing donor TK T
      cells. These cells later expanded and contributed to the replenishment of the
      recipient immune system with a diversified T-cell receptor repertoire. These
      results provide a rationale for designing the therapeutic scheme when using TK
      GCV suicide gene therapy in allogeneic HSCT.

PMID- 11567993
TI  - Membrane localization is not required for Mpl function in normal hematopoietic
      cells.
AB  - Cellular trafficking of growth factor receptors, including cross-talk among
      receptors at the cell surface, may be important for signal transduction in normal
      hematopoietic cells. To test this idea, the signaling domain of Mpl (the
      thrombopoietin receptor) was targeted to the plasma membrane, or to the cytoplasm
      of murine marrow cells, and the ability of the cells to proliferate and
      differentiate in response to Mpl dimerized at the plasma membrane or free in the
      cytoplasm was assessed. Constructs encoding the signaling domain of Mpl linked to
      an FK506 binding protein domain (to permit dimerization by the membrane-permeable
      ligand AP20187) with or without a myristylation sequence (to target the receptor
      to the plasma membrane) and a hemagglutinin epitope tag were generated and
      introduced into murine marrow cells using a murine stem cell virus (MSCV)-based
      retroviral vector. Both populations of transduced marrow cells proliferated in
      Iscoves modified Dulbecco medium-10% FCS-100 nM AP20187 without exogenous growth
      factors for more than 100 days and achieved greater than a 10(7)-fold expansion
      of cells by day 50 (n = 4 transductions). Growth was dimerizer dependent, and
      myeloid, erythroid, and megakaryocytic progenitors were generated. Activation of
      Mpl either at the plasma membrane or in the cytoplasm allowed for the terminal
      maturation of transduced progenitor cells. Introduction of membrane-targeted or
      cytoplasmic Mpl into fetal liver cells from homozygous JAK2 knock-out mice or
      wild-type littermates demonstrated that both forms of Mpl require JAK2 for
      signaling. These data show that the activation of Mpl independent of its normal
      plasma membrane location can support production of the full range of normal
      hematopoietic progenitor cells in vitro.

PMID- 11567994
TI  - Mpl ligand prevents lethal myelosuppression by inhibiting p53-dependent
      apoptosis.
AB  - A single dose of Mpl ligand (Mpl-L) given immediately after lethal DNA-damaging
      regimens prevents the death of mice. However, the mechanism of this
      myeloprotection is unknown. The induction of p53-dependent apoptosis in response
      to DNA damage signals suggests that immediate administration of Mpl-L may inhibit
      p53-dependent apoptosis. This hypothesis was tested by administering a single
      injection of pegylated murine Megakaryocyte Growth and Development Factor (PEG
      rmMGDF, a truncated recombinant Mpl-L) to p53(-/-) and wild-type mice immediately
      after carboplatin (80 mg/kg) and 7.5 Gy total body gamma-irradiation. PEG-rmMGDF
      was required to prevent the death of wild-type mice, whereas p53(-/-) mice
      survived with or without the exogenous cytokine. The degree of platelet
      depression and subsequent recovery was comparable in p53(-/-) mice to wild-type
      animals given PEG-rmMGDF. Hence, either Mpl-L administration or p53-deficiency
      protected multipotent hematopoietic progenitors and committed megakaryocyte
      precursors. The myelosuppressive regimen induced expression of p53 and the p53
      target, p21(Cipl) in wild-type bone marrow, indicating that Mpl-L acts downstream
      of p53 to prevent apoptosis. Constitutive expression of the proapoptotic protein
      Bax, was not further increased. Bax(-/-) mice survived the lethal regimen only
      when given PEG-rmMGDF; however, these Bax(-/-) mice showed more rapid
      hematopoietic recovery than did identically-treated wild-type mice. Therefore,
      administration of Mpl-L immediately after myelosuppressive chemotherapy or
      preparatory regimens for autologous bone marrow transplantation should prevent
      p53-dependent apoptosis, decrease myelosuppression, and reduce the need for
      platelet transfusions.

PMID- 11567995
TI  - Regulation of the inhibitor-of-apoptosis family member survivin in normal cord
      blood and bone marrow CD34(+) cells by hematopoietic growth factors: implication
      of survivin expression in normal hematopoiesis.
AB  - The inhibitor-of-apoptosis protein survivin is expressed in most cancers and
      leukemias and during fetal development, but not in most normal adult tissues.
      Survivin expression was analyzed in umbilical cord blood (UCB) and adult bone
      marrow CD34(+) cells and in the factor-dependent MO7e cell line; also
      investigated was whether survivin expression was regulated by hematopoietic
      growth factors. Survivin messsenger RNA (mRNA) and protein were expressed in
      fresh UCB and marrow CD34(+) cells. The combination of thrombopoietin, Flt3
      ligand, and stem cell factor upregulated survivin expression in CD34(+) cells
      within 24 hours; survivin expression was cell-cycle related and highest during
      G2/M, whereas growth-factor withdrawal resulted in decreased survivin expression.
      Cell-cycle fractionation of UCB CD34(+) with Hoechst-33342/pyronin-Y demonstrated
      that survivin message was undetectable in freshly isolated G0 cells, but present
      in G1 cells. After cytokine stimulation, survivin mRNA and protein expression
      were observed in both G0 and G1 CD34(+) cells as well as in cells that had
      progressed to S and G2/M phase, indicating that survivin expression is regulated
      in all phases of the cell cycle. This contrasts with the expression of survivin
      predominantly during G2/M in cancer cells. In CD34(+) cells and MO7e cells,
      growth factor-mediated upregulation of survivin was associated with inhibition of
      apoptosis, and downregulation of survivin was coincident with increased
      apoptosis. Furthermore, an inverse correlation between survivin and active
      caspase-3 was observed in CD34(+) cells. These findings demonstrate that survivin
      is not a cancer-specific antiapoptotic protein and plays a regulatory role in
      normal adult hematopoiesis.

PMID- 11567996
TI  - Interleukin-18 stimulates hematopoietic cytokine and growth factor formation and
      augments circulating granulocytes in mice.
AB  - Because interleukin-18 (IL-18) is similar to IL-1 and is known to be involved in
      the hematopoietic progenitor cell growth, the effect of IL-18 on circulating cell
      populations was examined. Repeated administration of IL-18 induced significant
      amounts of neutrophilia in mice. In parallel, high levels of interferon-gamma
      (IFN-gamma), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF)
      were detected in the serum of these mice. Interestingly, the cytokine profiles as
      well as the cell populations in circulation altered around 2 weeks after the
      beginning of IL-18 administration. A weak but definite eosinophilia was observed
      concurrently with the appearance of serum IL-5. Consistent with these
      observations, IL-18 induced secretion of IFN-gamma, GM-CSF, and IL-6 from
      splenocytes in culture. IL-18 also induced low levels of IL-5 in the splenocyte
      culture, which was inhibited by IL-12. However, markedly high levels of IL-5 were
      secreted into the culture medium when splenocytes from IFN-gamma-deficient mice
      were stimulated by IL-18. CD4(+) T cells strongly responded to IL-18 to secrete
      IL-5 and GM-CSF. IL-18 stimulated secretion of IL-6 and expression of G-CSF mRNA
      in splenic adherent cells. Expression of IL-18 receptors was detected in CD4(+) T
      cells and splenic adherent cells (macrophages). These results show that IL-18
      stimulates CD4(+) T cells and macrophages to secrete IL-5, GM-CSF, IL-6, and
      granulocyte-colony stimulating factor in the absence of IL-12, which in turn
      induces hematopoietic cell proliferation causing neutrophilia and eosinophilia in
      mice.

PMID- 11567997
TI  - Differential homing and engraftment properties of hematopoietic progenitor cells
      from murine bone marrow, mobilized peripheral blood, and fetal liver.
AB  - The rate of reconstitution following hematopoietic stem cell (HSC)
      transplantation differs widely depending on the tissue source of the cells
      infused. To test the hypothesis that variability in engraftment kinetics is
      related to differences in the efficiency with which intravenously transplanted
      HSCs "home" to the bone marrow (BM), the homing properties of murine fetal liver
      (FL), adult BM, and mobilized peripheral blood (MPB) cells were compared.
      Lethally irradiated mice transplanted with 2 x 10(6) FL, BM, or MPB cells
      exhibited sequentially slower recovery of circulating leukocytes and platelets
      that correlates with the progressively lower frequency of colony-forming cells
      (CFCs) in these tissues. However, differences in the rate and degree of early and
      long-term reconstitution were maintained even after infusing equal numbers of
      CFCs derived from FL, BM, and MPB. To compare the homing of progenitors from
      these tissues, cells were labeled with fluorescent PKH26 dye and injected into
      lethally irradiated hosts. Three hours later, PKH26(+) cells were reisolated from
      the BM and spleen by fluorescence-activated cell sorting and assayed for in vitro
      CFCs. Despite the higher level of very late antigen (VLA)-2, VLA-4, and VLA-5 on
      Sca-1(+)c-kit(+) cells from FL compared to BM, 10-fold fewer FL CFCs homed to
      hematopoietic organs than those from BM. MPB cells homed slightly better, but
      still less efficiently than BM cells. Therefore, clonogenic cells from different
      tissues exhibit striking variations in homing efficiency that does not
      necessarily correlate with engraftment kinetics. Homing is likely counterbalanced
      by intrinsic differences in proliferative potential that ultimately determine the
      rate of hematopoietic reconstitution.

PMID- 11567998
TI  - Histone deacetylase 3 associates with and represses the transcription factor GATA
      2.
AB  - The zinc finger transcription factor GATA-2 plays a critical role in the survival
      and proliferation of hematopoietic stem cells. This study examined the
      interaction of GATA-2 with histone deacetylases (HDACs) to define the involvement
      of HDACs in the regulation of GATA-2 function. GATA-2 directly associates with
      HDAC3 but not with HDAC1. Consistent with this, HDAC3 suppressed the
      transcriptional potential of GATA-2, whereas HDAC1 did not affect GATA-2
      dependent transcription. Results further demonstrated that GATA-2 and HDAC3
      colocalized in the nucleus. These results identify GATA-2 as a nuclear target for
      HDAC3-mediated repression. Furthermore, GATA-2 also directly associated with
      HDAC5 but not with other class II HDACs examined, that is, HDAC4 and HDAC6. This
      is the first demonstration that a tissue-specific transcription factor directly
      and selectively interacts with HDAC3 and HDAC5 among HDAC family members.

PMID- 11567999
TI  - Decorin inhibits macrophage colony-stimulating factor proliferation of
      macrophages and enhances cell survival through induction of p27(Kip1) and
      p21(Waf1).
AB  - Decorin is a small proteoglycan that is ubiquitous in the extracellular matrix of
      mammalian tissues. It has been extensively demonstrated that decorin inhibits
      tumor cell growth; however, no data have been reported on the effects of decorin
      in normal cells. Using nontransformed macrophages from bone marrow, results of
      this study showed that decorin inhibits macrophage colony-stimulating factor (M
      CSF)-dependent proliferation by inducing blockage at the G(1) phase of the cell
      cycle without affecting cell viability. In addition, decorin rescues macrophages
      from the induction of apoptosis after growth factor withdrawal. Decorin induces
      the expression of the cdk inhibitors p21(Waf1) and p27(Kip1). Using macrophages
      from mice where these genes have been disrupted, inhibition of proliferation
      mediated by decorin is related to p27(Kip1) expression, whereas p21(Waf1)
      expression is necessary to protect macrophages from apoptosis. Decorin also
      inhibits M-CSF-dependent expression of MKP-1 and extends the kinetics of ERK
      activity, which is characteristic when macrophages become activated instead of
      proliferating. The effect of decorin on macrophages is not due to its interaction
      with epidermal growth factor or interferon-gamma receptors. Furthermore, decorin
      increases macrophage adhesion to the extracellular matrix, and this may be
      partially responsible for the expression of p27(Kip1) and the modification of ERK
      activity, but not for the increased cell survival.

PMID- 11568000
TI  - ALCAM (CD166): its role in hematopoietic and endothelial development.
AB  - A critical role for the endothelium of yolk sac and dorsal aorta has been shown
      in embryonic hematopoiesis. A stromal cell line derived from yolk sac, YSCL-72,
      has been chosen to search for a novel molecule associated with embryonic
      hematopoiesis. Analysis between YSCL-72 and an adult aorta-derived endothelial
      cell line, EOMA, demonstrated that activated leukocyte cell adhesion molecule
      (ALCAM, or CD166) was specifically expressed in YSCL-72 but not in EOMA.
      Immunohistochemical study showed that ALCAM was expressed in the endothelium of
      yolk sac and dorsal aorta but not in adult aorta. ALCAM-transfected EOMA cells
      supported development of hematopoietic progenitor cells compared with vector
      transfected EOMA cells, suggesting that ALCAM appeared to be crucial for
      hematopoiesis. In addition, ALCAM was found to be involved in capillary tube
      formation and hemangioblast differentiation. Taken together with these findings,
      ALCAM is highly associated not only with embryonic hematopoiesis but also
      vasculoangiogenesis.

PMID- 11568001
TI  - Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector
      function in situ.
AB  - Interleukin-10 (IL-10) is a multifunctional cytokine that can exert suppressive
      and stimulatory effects on T cells. It was investigated whether IL-10 could serve
      as an immunostimulant for specific CD8(+) cytotoxic T cell (CTL) in vivo after
      vaccination and, if so, under what conditions. In tumor prevention models,
      administration of IL-10 before, or soon after, peptide-pulsed primary dendritic
      cell immunization resulted in immune suppression and enhanced tumor progression.
      Injection of IL-10, however, just after a booster vaccine significantly enhanced
      antitumor immunity and vaccine efficacy. Analysis of spleen cells derived from
      these latter animals 3 weeks after IL-10 treatment revealed that the number of
      CD8(+) CD44(hi) CD122(+) T cells had increased and that antigen-specific
      proliferation in vitro was enhanced. Although cytotoxicity assays did not support
      differences between the various treatment groups, 2 more sensitive assays
      measuring antigen-specific interferon-gamma production at the single-cell level
      demonstrated increases in the number of antigen-specific responder T cells in
      animals in the vaccine/IL-10 treatment group. Thus, IL-10 may maintain the number
      of antitumor CD8(+) T cells. In adoptive transfer studies, the ability of IL-10
      to maintain CTL function could be enhanced by the depletion of CD4(+) T cells.
      This suggests that IL-10 mediates contrasting effects on both CD4(+) and CD8(+) T
      cells that result in either immune dampening or immune potentiation in situ,
      respectively. Appreciation of this dichotomy in IL-10 immunobiology may allow for
      the design of more effective cancer vaccines designed to activate and maintain
      specific CD8(+) T-cell effector function in situ.

PMID- 11568002
TI  - CD8(+) T lymphocytes induce polarized exocytosis of secretory lysosomes by
      dendritic cells with release of interleukin-1beta and cathepsin D.
AB  - We recently reported that human dendritic cells release the leaderless secretory
      protein interleukin-1beta (IL-1beta) following specific interaction with
      alloreactive T lymphocytes. To clarify the molecular mechanism underlying this
      secretion, this study investigated the intracellular trafficking of IL-1beta in
      dendritic cells and the signal(s) regulating its release. Results show that a
      fraction of the intracellular IL-1beta precursor colocalizes with the hydrolase
      cathepsin D in endolysosomes of dendritic cells; secretion of both proteins is
      elicited by stimuli that induce intracellular calcium increases. Alloreactive
      CD8(+) T lymphocytes generate a Ca(++) influx in dendritic cells followed by
      enrichment in endolysosomes containing IL-1beta and cathepsin D beneath the
      membrane in contact with T cells. These events result in polarized exocytosis of
      secretory lysosomes, mediated by microtubules, with release of IL-1beta and
      cathepsin D toward the interacting CD8(+) T cell.

PMID- 11568003
TI  - Sperm protein 17 is expressed on normal and malignant lymphocytes and promotes
      heparan sulfate-mediated cell-cell adhesion.
AB  - Sperm protein 17 (Sp17) is a highly conserved mammalian protein present on
      acrosome-reacted sperm that is thought to promote fertilization by binding
      sulfated carbohydrates of the oocyte zona pellucida. Although Sp17 was originally
      described as a testis-specific antigen, emerging evidence indicates that it may
      be more ubiquitously expressed than was previously thought. With the use of a
      specific antiserum, Sp17 was found to be present on the surface of malignant
      lymphoid cells, including B- and T-lymphoid cell lines, and on the surface of
      primary cells isolated from 2 patients having B-lymphoid tumors. Surprisingly,
      circulating B lymphocytes isolated from healthy volunteers also expressed Sp17,
      while circulating T lymphocytes exhibited only very weak expression. The role of
      Sp17 in promoting lymphoid cell adhesion was addressed with the use of
      recombinant Sp17 (rSp17). The rSp17 binds to the surface of myeloma cells but not
      to cells pretreated with heparitinase, an enzyme that removes heparan sulfate
      from the cell surface. Moreover, rSp17 promotes extensive aggregation of cells
      that express the syndecan-1 heparan sulfate proteoglycan, but in contrast, cells
      lacking syndecan-1 expression fail to aggregate in the presence of rSp17. These
      findings suggest that Sp17 promotes heparan sulfate-mediated cell aggregation and
      thereby plays a role in regulating adhesion and migration of normal and malignant
      lymphocytes.

PMID- 11568004
TI  - Interleukin-7 and infection itself by human immunodeficiency virus 1 favor virus
      persistence in mature CD4(+)CD8(-)CD3(+) thymocytes through sustained induction
      of Bcl-2.
AB  - The sequence of events and the mechanisms leading to the destruction of the
      thymus during human immunodeficiency virus (HIV) infection are still poorly
      characterized. Investigated here are the survival capacity on HIV-1 infection of
      the mature single-positive CD4(+)CD8(-)CD3(+) (SP CD4(+)) and the intermediate
      CD4(+) CD8(-)CD3(-) thymocytes previously shown to be able to replicate the virus
      in the thymic microenvironment. It is demonstrated that the mature SP CD4(+)
      thymocytes exhibit a high survival capacity despite the production of a high
      yield of viruses. Interleukin-7, reported to be a crucial cofactor of tumor
      necrosis factor (TNF) to promote HIV replication, is shown here to counteract the
      apoptotic activity of TNF. Resistance to apoptosis of SP CD4(+) cells is
      conferred by a high expression of the IL-7 receptor (IL-7R) associated with the
      capacity of IL-7 to permanently up-regulate Bcl-2. In addition, this high Bcl-2
      level is further enhanced by infection itself. In contrast, intermediate
      thymocytes, which replicate the virus at a lower level, are more sensitive to
      apoptosis, and their differentiation into double-positive CD4(+)CD8(+)CD3(-) (DP
      CD3(-)) cells strongly increases their death rate on infection. This sensitivity
      is related to a lower expression of IL-7R and Bcl-2 in intermediate thymocytes,
      which further decreases at the DP CD3(-) stage. In addition, a decreased level of
      Bcl-2 is observed in this subset during infection. Altogether these data suggest
      that in vivo, HIV infection might create a persistent virus reservoir within the
      SP CD4(+) thymocytes, whereas the later infection of intermediate cells might
      lead to thymopoiesis failure.

PMID- 11568005
TI  - Extracellular signal-regulated protein kinase signaling pathway negatively
      regulates the phenotypic and functional maturation of monocyte-derived human
      dendritic cells.
AB  - Dendritic cells (DC) are highly specialized antigen-presenting cells that on
      activation by inflammatory stimuli (eg, tumor necrosis factor alpha [TNF-alpha]
      and interleukin-1beta [IL-1beta]) or infectious agents (eg, lipopolysaccharide
      [LPS]), mature and migrate into lymphoid organs. During maturation, DC acquire
      the capacity to prime and polarize resting naive T lymphocytes. Maturation of
      monocyte-derived DC (MDDC) is inhibited by the p38 mitogen-activated protein
      kinase (MAPK) inhibitor SB203580. This study found that in the presence of the
      mitogen-activated protein kinase kinase 1-extracellular signal-regulated kinase
      (ERK) inhibitors PD98059 or U0126, TNF-alpha- and LPS-induced phenotypic and
      functional maturation is enhanced. ERK pathway inhibitors increased expression of
      major histocompatibility complex and costimulatory molecules; loss of mannose
      receptor-mediated endocytic activity; nuclear factor-kappaB DNA-binding activity;
      release of IL-12 p40; and allogeneic T-cell proliferation induced by LPS or TNF
      alpha. Moreover, PD98059 and U0126 enhanced LPS-triggered production of IL-12
      p70. In agreement with the effect of ERK inhibitors, maturation of MDDC was
      delayed in the presence of serum, an effect that was reversed by U0126. These
      results indicate that the ERK and p38 MAPK signaling pathways differentially
      regulate maturation of MDDC and suggest that their relative levels of activation
      might modulate the initial commitment of naive T-helper (Th) cells toward Th1 or
      Th2 subsets. The findings also suggest that maturation of MDDC might be
      pharmacologically modified by altering the relative levels of activation of both
      intracellular signaling routes.

PMID- 11568007
TI  - HV(MNE), a novel lymphocryptovirus related to Epstein-Barr virus, induces
      lymphoma in New Zealand White rabbits.
AB  - HV(MNE) is a novel Epstein-Barr (EBV)-like virus isolated from a Macaca
      nemestrina with CD8(+) T-cell mycosis fungoides-cutaneous T-cell lymphoma. Here
      it is demonstrated that intravenous inoculation of irradiated HV(MNE)-infected T
      cells or cell-free virus from the J94356(PBMC) cell line in New Zealand White
      rabbits results in seroconversion to the viral capsid antigen (VCA) of EBV; all
      animals that seroconverted to VCA developed malignant lymphoma within months of
      inoculation. In contrast, control rabbits, inoculated with heat-inactivated
      culture supernatants from the same cell line, failed to seroconvert to VCA and
      did not develop disease. Disseminated lymphoma cells of mixed origin were
      detected in most vital organs, including the spleen, liver, lungs, kidneys, and
      heart of the affected rabbits. Neoplastic infiltrates were also observed in lymph
      nodes, thymus, skin, and subcutaneous tissues. HV(MNE) DNA and EBV-like RNA
      expression was demonstrated in the lymphomatous organs and in 2 transformed T
      cell lines, one established from the lymph node and the other from the blood of
      the 2 lymphomatous animals. Analysis of one of these T-cell lines demonstrated
      the persistence of HV(MNE) DNA, expression of an LMP1-like protein, and
      acquisition of interleukin-2 independence, and constitutive activation of the
      Jak/STAT pathway. Thus, HV(MNE) in rabbits provides a valuable animal model for
      human T-cell lymphoma whereby genetic determinants for T-cell transformation by
      this EBV-like animal virus can be studied.

PMID- 11568006
TI  - Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced
      apoptosis in multiple myeloma.
AB  - It has been reported that interferons (IFNs) may have antitumor activity in
      multiple myeloma (MM). The mechanism for their effect on MM, however, remains
      elusive. This study shows that IFN-alpha and -beta, but not -gamma, induce
      apoptosis characterized by Annexin V positivity, nuclear fragmentation and
      condensation, and loss of clonogenicity in 3 MM cell lines (U266, RPMI-8266, and
      NCI-H929), and in plasma cells from 10 patients with MM. Apo2 ligand (Apo2L, also
      TRAIL) induction was one of the earliest events following IFN administration in
      U266 cells. Treatment of these cells with TRAIL, but not with Fas agonistic
      antibodies, induces apoptosis. Cell death induced by IFNs and Apo2L in U266 cells
      was partially blocked by a dominant-negative Apo2L receptor, DR5, demonstrating
      the functional significance of Apo2L induction. This study shows that IFNs
      activate caspases and the mitochondrial-dependent apoptotic pathway, possibly
      mediated by Apo2L production. Thus, IFN-alpha and -beta induce cytochrome c
      release from mitochondria starting at 12 hours, with an amplified release seen at
      48 hours. Moreover, Bid cleavage precedes the initial cytochrome c release,
      whereas the late, amplified cytochrome c release coincides with changes in levels
      of Bcl-2, Bcl-X(L), and reduction of mitochondrial membrane potential. These
      results link the Apo2L induction and modulation of Bcl-2 family proteins to
      mitochondrial dysfunction. Furthermore, IFNs and Apo2L induce cell death of
      CD38(+)/CD45(-/dim) plasma cells, without significant effect on nonplasma blood
      cells, in a caspase and Bcl-2 cleavage-dependent manner. These results warrant
      further clinical studies with IFNs and Apo2L in MM.

PMID- 11568008
TI  - Expression of mast cell tryptase by myeloblasts in a group of patients with acute
      myeloid leukemia.
AB  - alpha- and beta-tryptase genes encode serine proteases that are abundantly
      expressed by mast cells. Under physiologic conditions other myeloid cells are
      virtually tryptase negative. However, tryptases are also expressed in several
      myeloid leukemia cell lines. In this study, serum total tryptase levels were
      determined in 150 patients with acute leukemias (de novo acute myeloid leukemia
      [AML], n = 108; secondary AML, n = 25; acute lymphoid leukemia [ALL], n = 17) by
      fluoroenzyme immunoassay. In healthy subjects (n = 30), tryptase levels ranged
      between 2.0 and 12.6 ng/mL. Elevated tryptase levels (> 15) were detected in 42
      (39%) of 108 patients with de novo AML and in 11 (44%) of 25 patients with
      secondary AML. No elevated tryptase levels were found in patients with ALL. In de
      novo AML, elevated tryptase levels were frequently detected in patients with
      French-American-British classification M0 (6 of 9), M2 (9 of 14), M3 (4 of 6),
      and M4eo (7 of 7), and less frequently in M1 (7 of 20), M4 (6 of 26), M5 (2 of
      18), M6 (0 of 5), or M7 (1 of 3). The highest tryptase levels were found in M4eo.
      Immunohistochemical staining of bone marrow sections with anti-tryptase antibody
      as well as immunoelectron microscopy revealed tryptase expression in the
      cytoplasm of myeloblasts. As assessed by Northern blotting and reverse
      transcriptase-polymerase chain reaction, AML cells expressed alpha-tryptase
      messenger RNA (mRNA) but little or no beta-tryptase mRNA. In AML patients with
      elevated serum tryptase before chemotherapy, who entered complete remission,
      tryptase levels returned to normal or near normal values. Blast cell persistence
      or regrowth was associated with a persistently elevated level or recurrent
      increase of tryptase. Together, tryptase is expressed in myeloblasts in a group
      of AML and may serve as a useful disease-related marker.

PMID- 11568009
TI  - Expression of scinderin in megakaryoblastic leukemia cells induces
      differentiation, maturation, and apoptosis with release of plateletlike particles
      and inhibits proliferation and tumorigenesis.
AB  - Rapid proliferation of atypical megakaryoblasts is a characteristic of
      megakaryoblastic leukemia. Cells from patients with this disorder and cell lines
      established from this type of leukemia showed the presence of gelsolin but the
      absence of scinderin expression, 2 filamentous actin-severing proteins present in
      normal megakaryocytes and platelets. Vector-mediated expression of scinderin in
      the megakaryoblastic cell line MEG-01 induced a decrease in both F-actin and
      gelsolin. This was accompanied by increased Rac2 expression and by activation of
      the PAK/MEKK.SEK/JNK/c-jun, c-fos transduction pathway. The Raf/MEK/ERK pathway
      was also activated in these cells. Transduction pathway activation was followed
      by cell differentiation, polyploidization, maturation, and apoptosis with release
      of platelet-like particles. Particles expressed surface CD41a antigen
      (glycoprotein IIb/IIIa or fibrinogen receptor), had dense bodies, high-affinity
      serotonin transport, and circular array of microtubules. Treatment of particles
      with thrombin induced serotonin release and aggregation that was blocked by CD41a
      antibodies. PAC-1 antibodies also blocked aggregation. Exposure of cells to
      PD98059, a blocker of MEK, inhibited antigen CD41a expression, increases in cell
      volume, and number of protoplasmic extensions. Cell proliferation and cell
      ability to form tumors in nude mice were also inhibited by the expression of
      scinderin. MEG-01 cells expressing scinderin had the same fate in vivo as in
      culture. Thus, when injected into nude mice, they entered apoptosis and released
      platelet-like particles. The lack of scinderin expression in megakaryoblastic
      leukemia cells seems to be responsible for their inability to enter into
      differentiation and maturation pathways characteristic of their normal
      counterparts.

PMID- 11568010
TI  - Activation of the nitric oxide synthase pathway represents a key component of
      tumor necrosis factor-related apoptosis-inducing ligand-mediated cytotoxicity on
      hematologic malignancies.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induced
      both cytotoxic (apoptosis) and cytostatic (cell cycle perturbation) effects on
      the human myeloid K562 cell line. TRAIL stimulated caspase 3 and nitric oxide
      synthase (NOS) activities, and both pathways cooperate in mediating inhibition of
      K562 survival/growth. This was demonstrated by the ability of z-VAD-fmk, a broad
      inhibitor of effector caspases, and N-nitro-L-arginine methyl ester (L-NAME), an
      NOS pharmacologic inhibitor, to completely (z-VAD-fmk) or partially (L-NAME)
      suppress the TRAIL-mediated inhibitory activity. Moreover, z-VAD-fmk was able to
      block TRAIL-mediated apoptosis and cell cycle abnormalities and increase of NOS
      activity. The addition of the NO donor sodium nitroprusside (SNP) to K562 cells
      reproduced the cytostatic effect of TRAIL without inducing apoptosis. When TRAIL
      was associated to SNP, a synergistic increase of apoptosis and inhibition of
      clonogenic activity was observed in K562 cells as well as in other myeloblastic
      (HEL, HL-60), lymphoblastic (Jurkat, SupT1), and multiple myeloma (RPMI 8226)
      cell lines. Although SNP greatly augmented TRAIL-mediated antileukemic activity
      also on primary leukemic blasts, normal erythroid and granulocytic cells were
      less sensitive to the cytotoxicity mediated by TRAIL with or without SNP. These
      data indicate that TRAIL promotes cytotoxicity in leukemic cells by activating
      effector caspases, which directly lead to apoptosis and stimulate NO production,
      which mediates cell cycle abnormalities. Both mechanisms seem to be essential for
      TRAIL-mediated cytotoxicity.

PMID- 11568011
TI  - Hypodiploidy is a major prognostic factor in multiple myeloma.
AB  - Conventional karyotypes performed before any treatment in 208 patients with
      multiple myeloma were reviewed by the Groupe Francais de Cytogenetique
      Hematologique. A total of 138 patients displayed complex chromosomal
      abnormalities (CCAs). According to the chromosome number pattern, a first group
      of 75 patients had a hyperdiploid karyotype. A second group of 63 patients
      referred to as the hypodiploid group had either pseudodiploid, hypodiploid, or
      near-tetraploid karyotypes. Of 159 treated patients available for survival
      analysis, 116 had an abnormal karyotype. The comparison of overall survival (OS)
      between hyperdiploid and hypodiploid patients showed a highly significant
      difference (median OS 33.8 vs 12.6 months, respectively, P <.001). The presence
      of 14q32 rearrangements (36 of 116 patients) worsened the prognosis (median OS
      17.6 vs 29.9 months, P <.02). The presence of chromosome 13q abnormalities (13qA,
      63 patients) did not modify OS in CCA patients (median OS 20.6 vs 27.8 months, P
      <.59). However, taking into account the whole series including normal karyotypes,
      13qA (63 of 159 patients) had a significant impact on OS (median 20.6 vs 37.1
      months, P <.04). In the same way, the presence of a hypodiploid karyotype (52 of
      159 patients) had a strong prognostic value (OS 12.8 vs 44.5 months, P <.000 01).
      A multivariate analysis including stage, beta2-microglobulin, bone marrow
      plasmocytosis, treatment type, 13qA, and hyperdiploidy and hypodiploidy showed
      that a hypodiploid karyotype was the first independent factor for OS (P <.001),
      followed by treatment approach. These results confirm that the chromosome number
      pattern of malignant plasma cells is a very powerful prognostic factor in newly
      diagnosed multiple myeloma patients.

PMID- 11568012
TI  - Interleukin-5 inhibits translocation of Bax to the mitochondria, cytochrome c
      release, and activation of caspases in human eosinophils.
AB  - The apoptosis and subsequent clearance of eosinophils without histotoxic mediator
      release is thought to be crucial in the resolution of airway inflammation in
      asthma. Interleukin-5 (IL-5) is a potent suppressor of eosinophil apoptosis. The
      mechanism by which IL-5 inhibits spontaneous eosinophil apoptosis was
      investigated. Freshly isolated eosinophils constitutively expressed the
      conformationally active form of Bax in the cytosol and nucleus. During
      spontaneous and staurosporine-induced apoptosis, Bax underwent a caspase
      independent translocation to the mitochondria, which was inhibited by IL-5.
      Eosinophil apoptosis was associated with the release of cytochrome c from the
      mitochondria, which was also inhibited by IL-5. IL-5 and the cell-permeable
      caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone (z
      VAD.fmk), prevented phosphatidylserine (PS) externalization, although only IL-5
      inhibited loss of mitochondrial membrane potential (DeltaPsim). Peripheral blood
      eosinophils endogenously expressed "initiator" caspase-8 and -9, and "effector"
      caspase-3, -6, and -7. Spontaneous eosinophil apoptosis was associated with
      processing of caspase-3, -6, -7, -8, and -9. IL-5 and z-VAD.fmk prevented caspase
      activation in spontaneous apoptosis. The results suggest that spontaneous
      eosinophil apoptosis involves Bax translocation to the mitochondria, cytochrome c
      release, caspase-independent perturbation of the mitochondrial membrane, and
      subsequent activation of caspases. IL-5 inhibits spontaneous eosinophil apoptosis
      at a site upstream of Bax translocation.

PMID- 11568013
TI  - GATA1-Cre mediates Piga gene inactivation in the erythroid/megakaryocytic lineage
      and leads to circulating red cells with a partial deficiency in glycosyl
      phosphatidylinositol-linked proteins (paroxysmal nocturnal hemoglobinuria type II
      cells).
AB  - Patients with paroxysmal nocturnal hemoglobinuria (PNH) have blood cells
      deficient in glycosyl phosphatidylinositol (GPI)-linked proteins owing to a
      somatic mutation in the X-linked PIGA gene. To target Piga recombination to the
      erythroid/megakaryocytic lineage in mice, the Cre/loxP system was used, and Cre
      was expressed under the transcriptional regulatory sequences of GATA-1. Breeding
      of GATA1-cre (G) transgenic mice with mice carrying a floxed Piga (L) allele was
      associated with high embryonic lethality. However, double-transgenic (GL) mice
      that escaped early recombination looked healthy and were observed for 16 months.
      Flow cytometric analysis of peripheral blood cells showed that GL mice had up to
      100% of red cells deficient in GPI-linked proteins. The loss of GPI-linked
      proteins on the cell surface occurred late in erythroid differentiation, causing
      a proportion of red cells to express low residual levels of GPI-linked proteins.
      Red cells with residual expression of GPI-linked proteins showed an intermediate
      sensitivity toward complement and thus resemble PNH type II cells in patients
      with PNH. Recombination of the floxed Piga allele was also detected in cultured
      megakaryocytes, mast cells, and eosinophils, but not in neutrophils, lymphocytes,
      or nonhematopoietic tissues. In summary, GATA1-Cre causes high-efficiency Piga
      gene inactivation in a GATA-1-specific pattern. For the first time, mice were
      generated that have almost 100% of red cells deficient in GPI-linked proteins.
      These animals will be valuable to further investigate the consequences of GPI
      anchor deficiency on erythroid/megakaryocytic cells.

PMID- 11568014
TI  - Administration of interleukin-7 after allogeneic bone marrow transplantation
      improves immune reconstitution without aggravating graft-versus-host disease.
AB  - Prolonged immunodeficiency after allogeneic bone marrow transplantation (BMT)
      causes significant morbidity and mortality from infection. This study examined in
      murine models the effects of interleukin-7 (IL-7) given to young and middle-aged
      (9-month-old) recipients of major histocompatibility complex (MHC)-matched or 
      mismatched allogeneic BMT. Although administration of IL-7 from day 0 to 14 after
      syngeneic BMT promoted lymphoid reconstitution, this regimen was ineffective
      after allogeneic BMT. However, IL-7 administration from day 14 (or 21) to 27
      after allogeneic BMT accelerated restoration of the major lymphoid cell
      populations even in middle-aged recipients. This regimen significantly expanded
      donor-derived thymocytes and peripheral T cells, B-lineage cells in bone marrow
      and spleen, splenic natural killer (NK) cells, NK T cells, and monocytes and
      macrophages. Interestingly, although recipients treated with IL-7 had significant
      increases in CD4(+) and CD8(+) memory T-cell populations, increases in naive T
      cells were less profound. Most notable, however, were the observations that IL-7
      treatment did not exacerbate graft-versus-host disease (GVHD) in recipients of an
      MHC-matched BMT, and would ameliorate GVHD in recipients of a MHC-mismatched BMT.
      Nonetheless, graft-versus-leukemia (GVL) activity (measured against 32Dp210
      leukemia) remained intact. Although activated and memory CD4(+) and CD8(+) T
      cells normally express high levels of IL-7 receptor (IL-7R, CD127), activated and
      memory alloreactive donor-derived T cells from recipients of allogeneic BMT
      expressed little IL-7R. This might explain the failure of IL-7 administration to
      exacerbate GVHD. In conclusion, posttransplant IL-7 administration to recipients
      of an allogeneic BMT enhances lymphoid reconstitution without aggravating GVHD
      while preserving GVL.

PMID- 11568015
TI  - Translocations involving the immunoglobulin heavy-chain locus are possible early
      genetic events in patients with primary systemic amyloidosis.
AB  - Primary systemic amyloidosis (AL) is a plasma cell (PC) dyscrasia with clinical
      similarities to multiple myeloma (MM) and monoclonal gammopathy of undetermined
      significance (MGUS), but its molecular basis is poorly understood. Translocations
      at the immunoglobulin heavy-chain (IgH) locus, 14q32, are likely early genetic
      events in both MM and MGUS and involve several nonrandom, recurrent, partner
      chromosomes such as 11q13, 16q23, and 4p16.3. Given the similarities between MM,
      MGUS, and AL, bone marrow clonal PCs were evaluated in 29 patients with AL using
      interphase fluorescence in situ hybridization (FISH) combined with
      immunofluorescence detection of the cytoplasmic light-chain (cIg-FISH) for the
      presence of 14q32 translocations and the t(11;14)(q13;q32). Of 29 patients
      studied, 21 (72.4%) showed results compatible with the presence of a 14q32
      translocation, and 16 (76.2%) of those had translocation (11;14)(q13;q32) for an
      overall prevalence of the abnormality of 55%. IgH translocations are common in
      AL, especially the t(11;14)(q13;q32).

PMID- 11568016
TI  - Serum osteoprotegerin levels are reduced in patients with multiple myeloma with
      lytic bone disease.
AB  - Osteoprotegerin (OPG), the neutralizing decoy receptor for the osteoclast
      activator RANK ligand, was measured in serum taken from patients with multiple
      myeloma at the time of diagnosis. Median OPG was lower in the patients with
      myeloma (7.4 ng/mL; range, 2.6-80; n = 225) than in healthy age- and sex-matched
      controls (9.0 ng/mL; range 5.1-130; n = 40; P =.02). Importantly, OPG levels were
      associated with degree of radiographically assessed skeletal destruction (P
      =.01). The median OPG level in patients lacking osteolytic lesions was 9.1 ng/mL,
      as compared with 7.6 ng/mL and 7.0 ng/mL, respectively, in patients with minor or
      advanced osteolytic disease. Furthermore, OPG levels were associated with World
      Health Organization performance status (P =.003) and correlated to serum levels
      of carboxy-terminal propeptide of type I procollagen (PICP; P <.001) but not with
      clinical stage or survival. These findings suggest impaired OPG function in
      myeloma and give a rationale for OPG as a therapeutic agent against myeloma bone
      disease.

PMID- 11568017
TI  - Presence of N regions in the clonotypic DJ rearrangements of the immunoglobulin
      heavy-chain genes indicates an exquisitely short latency in t(4;11)-positive
      infant acute lymphoblastic leukemia.
AB  - Childhood acute lymphoblastic leukemia (ALL) is frequently initiated in utero at
      a time of developmentally regulated insertion of N regions into the DJ(H)
      rearrangements of immunoglobulin heavy-chain (Ig(H)) genes. Here it is shown that
      N regions are present in the clonotypic DJ(H) rearrangements in 11 of 12 infant
      ALLs with t(4;11). These data are compared with the 122 previously published
      DJ(H) sequences and were found to have a pattern similar to that of ALL in
      children older than 3 years at diagnosis but were unlike that in children younger
      than 3 years who predominantly lack N regions. These findings, therefore,
      indicate that t(4;11)-positive infant ALL is initiated later in fetal development
      than most B-cell precursor ALL from children younger than 3 years and that they
      have a shorter latency period already in utero.

PMID- 11568018
TI  - Distinct regulatory elements are required for faithful expression of human CD4 in
      T cells, macrophages, and dendritic cells of transgenic mice.
AB  - To identify the regulatory elements controlling expression of the human CD4
      (hCD4) gene in different cell types of the immune system, deletion and chimeric
      (human/murine) reporter genes were constructed and tested in transgenic (Tg)
      mice. Regulatory elements required for the proper hCD4 expression in the immature
      double-positive thymic T cells were identified in the enhancer and in the 3' end
      of intron 1. Expression of hCD4 in macrophages is controlled by at least 2 sets
      of regulatory elements: one present in front of exon 1 and the second at the 5'
      end of intron 1. The hCD4 elements required for expression on both myeloid and
      lymphoid CD8alpha(+) dendritic cells (DCs) from lymph node and thymus were found
      to be different from those required for macrophage expression. The results
      indicate that expression of hCD4 in T cells, macrophages, and DCs is controlled
      by distinct regulatory elements.

PMID- 11568019
TI  - ORP-3, a human oxysterol-binding protein gene differentially expressed in
      hematopoietic cells.
AB  - Using differential display polymerase chain reaction, a gene was identified in
      CD34(+)-enriched populations that had with low or absent expression in CD34(-)
      populations. The full coding sequence of this transcript was obtained, and the
      predicted protein has a high degree of homology to oxysterol-binding protein.
      This gene has been designated OSBP-related protein 3 (ORP-3). Expression of ORP-3
      was found to be 3- to 4-fold higher in CD34(+) cells than in CD34(-) cells.
      Additionally, expression of this gene was 2-fold higher in the more primitive
      subfraction of hematopoietic cells defined by the CD34(+)38(-) phenotype and was
      down-regulated with the proliferation and differentiation of CD34(+) cells. The
      ORP-3 predicted protein contains an oxysterol-binding domain. Well-characterized
      proteins expressing this domain bind oxysterols in a dose-dependent fashion.
      Biologic activities of oxysterols include inhibition of cholesterol biosynthesis
      and cell proliferation in a variety of cell types, among them hematopoietic
      cells. Characterization and differential expression of ORP-3 implicates a
      possible role in the mediation of oxysterol effects on hematopoiesis.

PMID- 11568020
TI  - Very long-term survival and durability of mitral valve repair for mitral valve
      prolapse.
AB  - BACKGROUND: Mitral regurgitation (MR) due to mitral valve prolapse (MVP) is often
      treatable by surgical repair. However, the very long-term (>10-year) durability
      of repair in both anterior leaflet prolapse (AL-MVP) and posterior leaflet
      prolapse (PL-MVP) is unknown. METHODS AND RESULTS: In 917 patients (aged 65+/-13
      years, 68% male), surgical correction of severe isolated MR due to MVP (679
      repairs and 238 replacements [MVRs]) was performed between 1980 and 1995.
      Survival after repair was better than survival after MVR for both PL-MVP (at 15
      years, 41+/-5% versus 31+/-6%, respectively; P=0.0003) and AL-MVP (at 14 years,
      42+/-8% versus 31+/-5%, respectively; P=0.003). In multivariate analysis
      adjusting for predictors of survival, repair was independently associated with
      lower mortality in PL-MVP (adjusted risk ratio [RR] 0.61, 95% CI 0.44 to 0.85;
      P=0.0034) and in AL-MVP (adjusted RR 0.67, 95% CI 0.47 to 0.96; P=0.028). The
      reoperation rate was not different after repair or MVR overall (at 19 years, 20+/
      5% for repair versus 23+/-5% for MVR; P=0.4) or separately in PL-MVP (P=0.3) or
      AL-MVP (P=0.3). However, the reoperation rate was higher after repair of AL-MVP
      than after repair of PL-MVP (at 15 years, 28+/-7% versus 11+/-3%, respectively;
      P=0.0006). From the 1980s to the 1990s, the RR of reoperation after repair of AL
      MVP versus PL-MVP did not change (RR 2.5 versus 2.7, respectively; P=0.58), but
      the absolute rate of reoperation decreased similarly in PL-MVP and AL-MVP (at 10
      years, from 10+/-3% to 5+/-2% and from 24+/-6% to 10+/-2%, respectively; P=0.04).
      CONCLUSIONS: In severe MR due to MVP, mitral valve repair compared with MVR
      provides improved very long-term survival after surgery for both AL-MVP and PL
      MVP. Reoperation is similarly required after repair or replacement but is more
      frequent after repair of AL-MVP. Recent improvement in long-term durability of
      repair suggests that it should be the preferred mode of surgical correction of
      MVP whether it affects anterior or posterior leaflets and is an additional
      incentive for early surgery of severe MR due to MVP.

PMID- 11568021
TI  - Very long-term results (more than 20 years) of valve repair with carpentier's
      techniques in nonrheumatic mitral valve insufficiency.
AB  - BACKGROUND: Mitral valve repair is considered the gold standard in surgery of
      degenerative mitral valve insufficiency (MVI), but the long-term results (>20
      years) are unknown. METHODS AND RESULTS: We reviewed the first 162 consecutive
      patients who underwent mitral valve repair between 1970 and 1984 for MVI due to
      nonrheumatic disease. The cause of MVI was degenerative in 146 patients (90%) and
      bacterial endocarditis in 16 patients (10%). MVI was isolated or, in 18 cases,
      associated with tricuspid insufficiency. The mean age of the 162 patients (104
      men and 58 women) was 56+/-10 years (age range 22 to 77 years). New York Heart
      Association functional class was I, II, III, and IV in 2%, 39%, 52%, and 7% of
      patients, respectively. The mean cardiothoracic ratio was 0.58+/-0.07 (0.4 to
      0.8), and 72 (45%) patients had atrial fibrillation. Valve analysis showed that
      the main mechanism of MVI was type II Carpentier's functional classification in
      152 patients. The leaflet prolapse involved the posterior leaflet in 93 patients,
      the anterior leaflet in 28 patients, and both leaflets in 31 patients. Surgical
      technique included a Carpentier's ring annuloplasty in all cases, a valve
      resection in 126 patients, and shortening or transposition of chordae in 49
      patients. During the first postoperative month, there were 3 deaths (1.9%) and 3
      reoperations (2 valve replacements and 1 repeat repair [1.9%]). Six patients were
      lost to follow-up. The remaining 151 patients with mitral valve repair were
      followed during a median of 17 years (range 1 to 29 years; 2273 patient-years).
      The 20-year Kaplan-Meier survival rate was 48% (95% CI 40% to 57%), which is
      similar to the survival rate for a normal population with the same age structure.
      The 20-year rates were 19.3% (95% CI 11% to 27%) for cardiac death and 26% (95%
      CI 17% to 35%) for cardiac morbidity/mortality (including death from a cardiac
      cause, stroke, and reoperation). During the 20 years of follow-up, 7 patients
      were underwent surgery at 3, 7, 7, 8, 8, 10, or 12 years after the initial
      operation. Valve replacement was carried out in 5 patients, and repeat repair was
      carried out in 2 patients. At the end of the study, 65 patients remained alive
      (median follow-up 19 years). Their median age was 76 years (age range 41 to 95
      years). All except 1 were in New York Heart Association functional class I/II.
      CONCLUSIONS: Mitral valve repair using Carpentier's technique in patients with
      nonrheumatic MVI provides excellent long-term results with a mortality rate
      similar to that of the general population and a very low incidence of
      reoperation.

PMID- 11568022
TI  - Long-term (29 years) results of reconstructive surgery in rheumatic mitral valve
      insufficiency.
AB  - BACKGROUND: Results of conservative surgery are well established in degenerative
      mitral valve (MV) insufficiency. However, there are controversies in rheumatic
      disease. This study is the evaluation of one center for rheumatic MV
      insufficiency based on a functional approach. METHODS AND RESULTS: From 1970 to
      1994, 951 patients with rheumatic MV insufficiency were operated on with the
      reconstructive techniques elaborated by Alain Carpentier. Aortic valve diseases
      were excluded. Mean age was 25.8 years (4 to 75), and sinus rhythm was present in
      63%. The functional classification used was type I, normal leaflet motion, 71
      patients (7%); type II, prolapsed leaflet, 311 patients (33%); and type III,
      restricted leaflet motion, 345 patients (36%). The combined lesion of prolapse of
      the anterior leaflet and restriction of the posterior was present in 224 patients
      (24%). Surgical techniques used were implantation of a prosthetic ring in 95%,
      shortening of the chords and leaflet enlargement with autologous pericardium, and
      commissurotomy. Hospital mortality rate was 2%. The mean follow-up was 12 years
      (maximum, 29 years): 8618 patients per year. Actuarial survival was 89+/-19% at
      10 years and 82+/-18% at 20 years. The rate of thromboembolic events was 0.4%
      patients per year (33 events), with 3 deaths. Freedom from reoperation was 82+/
      19% at 10 years and 55+/-25% at 20 years. The main cause (83%) of reoperation was
      progressive fibrosis of the MV. The actuarial rate of reoperation was 2% patients
      per year and was correlated to the degree of preoperative fibrosis. CONCLUSIONS:
      Conservative surgery of rheumatic MV insufficiency has a low hospital mortality
      rate and an acceptable rate of reoperation. The results are excellent regarding
      the minimal risk of thromboembolic events.

PMID- 11568023
TI  - Incidence, location, pathology, and significance of pulmonary homograft stenosis
      after the Ross operation.
AB  - BACKGROUND: The Ross operation has several theoretical advantages. However,
      concern exists regarding evolving pathology in the pulmonary homograft. METHODS
      AND RESULTS: Consecutive patients (n=144; mean age 31 years, range 2 months to 64
      years) undergoing the Ross operation were studied between 1993 and 2000.
      Echocardiographic examination of the pulmonary homograft was performed
      immediately after surgery, then at yearly intervals for a mean interval of 48
      months. Fifteen patients (mean age 37 years) in whom echocardiography revealed
      peak pulmonary gradients >/=30 mm Hg (mean 46+/-18 mm Hg) underwent MRI with
      velocity mapping in a Picker 1.5-T magnet. No patient had more than mild
      pulmonary regurgitation. Four patients required reoperation for rapidly
      progressive pulmonary homograft stenosis; in all 4, there was macroscopic and
      microscopic evidence of a pronounced chronic adventitial reaction, with
      perivascular infiltration producing extrinsic compression. Freedom from any
      pulmonary homograft stenosis at 7-year follow-up was 79.7%, with instantaneous
      hazard falling to zero after 4 years. Freedom from reoperation at 7 years was
      96.7%. In those studied with MRI, there was evidence of narrowing of the whole
      homograft or distal suture line in 14 of 15 patients, with obvious excess
      surrounding tissue in 11. Mean minimum diameter and peak velocity by MRI were
      11+/-2 mm and 3.2+/-0.7 m/s, respectively. Multivariate analysis of patient-,
      surgery-, and homograft-related variables did not reveal any significant risk
      factors for development of neopulmonary stenosis. CONCLUSIONS: Pulmonary
      homograft stenosis after the Ross operation is clinically important and appears
      to represent an early postoperative inflammatory reaction to the pulmonary
      homograft that leads to extrinsic compression and/or shrinkage.

PMID- 11568024
TI  - Time course of aortic valve function and root dimensions after subcoronary ross
      procedure for bicuspid versus tricuspid aortic valve disease.
AB  - BACKGROUND: The freestanding aortic root, which is the currently preferred
      operative technique for pulmonary autografts, is reported to dilate and
      potentially promote aortic insufficiency, which has led to a controversial debate
      on the appropriate surgical technique, especially for congenital bicuspid aortic
      valve disease. Desirable data on the time course of valve function and root
      dimensions for the alternative subcoronary technique comparing bicuspid and
      tricuspid aortic valve disease are scarce. METHODS AND RESULTS: Echocardiographic
      examinations of 31 patients with congenital bicuspid aortic valve disease (group
      A; age 50.5+/-11.0 years) and 51 patients with acquired tricuspid aortic valve
      disease (group B; age 48.1+/-15.7 years) who were operated on between June 1994
      and August 1998 were performed twice postoperatively. At first and second follow
      up, respectively, maximum (mean) pressure gradients were 6.0+/-2.0 (3.6+/-1.0)
      and 5.1+/-2.1 (2.9+/-1.1) mm Hg in group A and 6.5+/-3.5 (3.9+/-1.9) and 5.0+/
      1.7 (2.9+/-1.0) mm Hg in group B (P>0.05 between groups). In group A, grade 0
      aortic insufficiency at first and second follow-up occurred in 8 and 7 patients,
      respectively, grade 0-I in 12 and 9 patients, grade I in 9 and 11 patients, grade
      I-II in 1 and 0 patients, and grade II in 1 and 4 patients; in group B, grade 0
      aortic insufficiency occurred in 16 and 18 patients, grade 0-I in 16 and 8
      patients, grade I in 17 and 21 patients, grade I-II in 0 and 1 patient, and grade
      II in 0 and 1 patient (P>0.05). Aortic insufficiency decreased in 10 patients
      (17%). However, there was an overall tendency for aortic insufficiency to
      increase over time (n=23, 38%), although it remained subclinical. Aortic root
      dimensions did not differ between groups and were constant during follow-up.
      CONCLUSIONS: This study provides some evidence that the function of the
      subcoronary pulmonary autograft in bicuspid aortic valve disease is excellent,
      with stable root dimensions, and is not different from that of tricuspid aortic
      valves at least up to 5.5 years postoperatively, which suggests the subcoronary
      technique should be reconsidered.

PMID- 11568025
TI  - Does histocompatibility affect homograft valve function after the Ross procedure?
AB  - BACKGROUND: Homograft valves have been shown to be immunogenic, but it is unknown
      whether this affects valve function. Therefore, we prospectively studied the
      degree of histoincompatibility (defined as the number of human leukocyte antigen
      [HLA] mismatches between valve donor and recipient) and the response of the
      recipient (measured by antibodies against HLA) in relation to echocardiographic
      parameters of homograft valve function after the Ross procedure. METHODS AND
      RESULTS: Twenty-six patients (mean age 41+/-14 years; 20 males, 6 females) and
      the cryopreserved pulmonary homograft valves that were implanted during a Ross
      procedure were typed for HLA-A, HLA-B, and HLA-DR. After a mean follow-up of 15+/
      6 months, 14 (54%) of the patients were anti-HLA class I antibody positive. In
      all but 1 patient, these antibodies were shown to be donor specific. During
      follow-up, there was a significant increase of the maximal (+6.2+/-7.1 mm Hg) and
      mean (+3.2+/-4.3 mm Hg) transhomograft pressure gradients but not of homograft
      regurgitation. Neither the number of HLA mismatches nor antibody status was found
      to have significant impact on homograft valve function. In a multivariate
      analysis, smaller homograft size (P=0.001) and younger recipient age (P=0.044)
      were shown to be significantly associated with increased transhomograft pressure
      gradients. CONCLUSIONS: Implantation of a cryopreserved pulmonary homograft
      during the Ross procedure can induce a specific humoral response. We observed a
      significant increase of the transhomograft pressure gradients within 15+/-6
      months after surgery. For this period, we were unable to demonstrate a
      relationship between this increase and the degree of histoincompatibility.

PMID- 11568026
TI  - Edge-to-edge mitral repair: tension on the approximating suture and leaflet
      deformation during acute ischemic mitral regurgitation in the ovine heart.
AB  - BACKGROUND: Edge-to-edge approximation of the mitral valve leaflets (Alfieri
      procedure) is a novel surgical treatment for patients with ischemic mitral
      regurgitation (IMR). Long-term durability may be limited if abnormal mitral
      leaflet stresses result from this procedure. The aim of the current study was to
      measure Alfieri stitch tension (F(A)) and to explore its geometric determinants
      in an ovine model of acute IMR as a reflection of the mitral leaflet stresses
      imposed by the procedure. METHODS AND RESULTS: Eight sheep were studied
      immediately after surgical placement of (1) a force transducer interposed between
      sutures approximating the central leaflet edges and (2) radiopaque markers around
      the mitral annulus and leaflet edges. Computer-aided analysis of videofluorograms
      was used to obtained 3D marker coordinates. Simultaneous measurements of F(A),
      septal-lateral annular dimension (L(S-L)), leaflet edge separation (L(SEP)),
      anterior (L(AL)) and posterior (L(PL)) leaflet length, and hemodynamic variables
      were obtained at baseline (CTL) and during acute IMR (circumflex artery
      occlusion). F(A) was significantly elevated throughout the cardiac cycle during
      IMR compared with CTL, with maximum F(A) in diastole (0.26+/-0.05 versus 0.46+/
      0.08 N, CTL versus IMR; P<0.05). Multivariable analysis revealed L(S-L) as the
      single independent predictor of maximum F(A) (P<0.001). Positive linear
      correlations were shown between values of F(A) and L(AL) and L(PL) (dependent
      variables). CONCLUSIONS: These experimental data demonstrate higher F(A) during
      IMR and cyclic changes in F(A) closely paralleling changes in L(S-L), eg, being
      greatest in diastole when the annulus is largest. Increased F(A) during IMR is
      probably indicative of successful therapeutic intent, but higher diastolic
      leaflet stresses resulting from persistent or progressive mitral annular
      dilatation may adversely affect repair durability. This indirectly implies that
      concomitant mitral ring annuloplasty should be added to the Alfieri repair.

PMID- 11568027
TI  - Surgical management of left-sided carcinoid heart disease.
AB  - BACKGROUND: Carcinoid involvement of left-sided heart valves has been reported in
      patients with a patent foramen ovale, carcinoid tumor of the lung, and active
      carcinoid syndrome with high levels of serotonin. The present study details the
      clinical features and surgical management of patients with carcinoid heart
      disease affecting both left- and right-sided valves. METHODS AND RESULTS: Eleven
      patients (7 men, 4 women) with symptomatic carcinoid heart disease underwent
      surgery for left- and right-sided valve disease between 1989 and 1999. Mean age
      was 57+/-9 years, and median preoperative NYHA class was 3. All patients had
      metastatic carcinoid tumors and were on somatostatin analog. Of 11 patients, 5
      (45%) had a patent foramen ovale; 1 of these also had a primary lung carcinoid
      tumor. Surgery included tricuspid valve replacement in all patients, pulmonary
      valve replacement in 3 and valvectomy in 7, mitral valve replacement in 6 and
      repair in 1, aortic valve replacement in 4 and repair in 2, CABG in 2, and patent
      foramen ovale closure in 5. One myocardial metastatic carcinoid tumor was
      removed. There were 2 perioperative deaths. At a mean follow-up of 41 months, 4
      additional patients were dead. All but 1 surgical survivor initially improved
      >/=1 functional class. No patient required reoperation. CONCLUSIONS: Carcinoid
      heart disease may affect left- and right-sided valves and occurred without
      intracardiac shunting in 55% of this surgical series. Despite metastatic disease
      that limits longevity, operative survivors had improvement in functional
      capacity. Cardiac surgery should be considered for select patients with carcinoid
      heart disease affecting left- and right-sided valves.

PMID- 11568028
TI  - Anterior chordal transection impairs not only regional left ventricular function
      but also regional right ventricular function in mitral regurgitation.
AB  - BACKGROUND: Preservation of annuloventricular continuity through the chordae
      tendinae aims to maintain left ventricular (LV) function and thus improve
      postoperative prognosis. This study was designed to prospectively investigate the
      effect of anterior chordal transection on global and regional LV and right
      ventricular (RV) function in mitral regurgitation (MR). METHODS AND RESULTS:
      Sixty-five patients with severe MR underwent radionuclide angiography before and
      after either mitral valve (MV) repair (42 patients) or replacement with anterior
      chordal transection (23 patients). LV and RV ejection fractions (EF) were
      determined at rest. Both ventricles were divided into 9 regions to analyze
      regional EF and the effect of anteromedial translation related to surgery. After
      surgery there was a significant decrease in LVEF (P=0.038) and an increase in
      RVEF (P=0.036). However, LVEF did not change after MV repair (63.8+/-9.9% to
      62.6+/-10.3%), whereas RVEF improved (40.7+/-10.1% to 44.5+/-8.1%, P=0.027). In
      contrast, LVEF decreased after MV replacement (61.7+/-10.1% to 57.2+/-9.9%,
      P=0.03), and RVEF was unchanged (40.9+/-10.9% to 41.3+/-9.1%). LVEF 4 and 5, in
      the area of anterior papillary muscle insertion, were impaired after MV
      replacement compared with MV repair (region 4, 77.6+/-16.7% versus 87.7+/-10.8%,
      P=0.005, and region 5, 73.9+/-19.3% versus 89.9+/-13.1%, P<0.001). Moreover,
      anterior chordal transection led to a significant impairment in the apicoseptal
      region of the RV (RVEF 4, 50.3+/-15.6% versus 59.3+/-13.8%, P=0.02). CONCLUSIONS:
      Anterior chordal transection during MV replacement for MR impairs not only
      regional LV function but also regional RV function.

PMID- 11568029
TI  - Pathogenesis of mitral regurgitation in tachycardia-induced cardiomyopathy.
AB  - BACKGROUND: Dilated cardiomyopathy is often associated with mitral regurgitation
      (MR), or so-called functional MR, the mechanism of which continues to be debated.
      We studied the valvular and ventricular 3D geometric perturbations associated
      with MR in an ovine model of tachycardia-induced cardiomyopathy (TIC). METHODS
      AND RESULTS: Nine sheep underwent myocardial marker implantation in the left
      ventricle (LV), mitral annulus, and mitral leaflets. After 5 to 8 days, the
      animals were studied with biplane videofluoroscopy (baseline), and mitral
      competence was assessed by transesophageal echocardiography. Rapid ventricular
      pacing (180 to 230 bpm) was subsequently initiated for 15+/-6 days until the
      development of TIC and MR, whereupon biplane videofluoroscopy and transesophageal
      echocardiography studies were repeated. LV volume was calculated from the
      epicardial marker array. Valve closure time was defined as the time after end
      diastole when the distance between leaflet edge markers reached its minimal
      plateau. TIC resulted in increased LV end-diastolic volume (P=0.001) and LV end
      systolic volume (P=0.0001) and greater LV sphericity (P=0.02). MR increased
      significantly (grade 0.2+/-0.3 versus 2.2+/-0.9, P=0.0001), as did mitral annulus
      area (817+/-146 versus 1100+/-161 mm(2), P=0.0001) and mitral annulus septal
      lateral diameter (28.2+/-3.5 versus 35.1+/-2.6 mm, P=0.0001). Time of valve
      closure (70+/-18 versus 87+/-14 ms, P=0.23) and angular displacement of both the
      anterior (29+/-5 degrees versus 27+/-3 degrees, P=0.3) and posterior (55+/-15
      degrees versus 44+/-11 degrees, P=0.13) leaflet edges relative to the mitral
      annulus after valve closure did not change, but leaflet edge separation after
      closure increased (5.2+/-0.9 versus 6.8+/-1.2 mm, P=0.019). CONCLUSIONS: MR in
      TIC resulted from decreased leaflet coaptation secondary to annular dilatation in
      the septal-lateral direction. These data support the use of annular reduction
      procedures, such as rigid, complete ring annuloplasty, to address functional MR
      in patients with dilated cardiomyopathy.

PMID- 11568030
TI  - Regression of left ventricular hypertrophy after surgical therapy for aortic
      stenosis is associated with changes in extracellular matrix gene expression.
AB  - BACKGROUND: Regression of left ventricular hypertrophy (LVH) after surgical
      correction for aortic stenosis is not fully understood on the molecular level.
      The aim of this study was to examine whether there is an association between LVH
      regression and extracellular matrix (ECM) gene expression. METHODS AND RESULTS: A
      standard model of controlled LVH induction by supracoronary banding (A=baseline)
      was applied in 44 growing sheep (age, 6 to 8 months). Surgical correction to
      release the pressure gradient was performed 8.3+/-1 months later (B). The animals
      were killed after another 10.1+/-2 months (C). At all time points, hemodynamic
      evaluations and quantitative analysis of mRNA and protein expression for matrix
      metalloproteinases (MMP) and their tissue inhibitors (TIMP) was performed. Left
      ventricular mass index was 82+/-21 (A) versus 150+/-33 (B), P<0.01, and 78+/-18
      g/m(2) (C), P<0.01. Left ventricular function and cardiac index remained stable.
      Myocardial fiber diameter index was 9.1+/-1.2 (A) versus 12.3+/-1.4 (B), P<0.01,
      and 8.4+/-1.3 micrometer/m(2) (C), P<0.01. In parallel to the development of LVH
      at B, gene expression was increased significantly for MMP-1, MMP-2, MMP-3, and
      MMP-9 and for TIMP-1 and TIMP-2 and decreased significantly for TIMP-3. After
      surgical correction (C), there was a complete regression of gene expression to
      baseline measures. CONCLUSIONS: Controlled induction of compensated LVH leads to
      significant increase in ECM gene expression. The regression of LVH after surgical
      therapy is associated with complete regression of ECM gene expression. However,
      no cause-and-effect relation could be demonstrated.

PMID- 11568031
TI  - Influence of atrial fibrillation on outcome following mitral valve repair.
AB  - BACKGROUND: To investigate the outcome of patients in atrial fibrillation (AF)
      following mitral valve repair, clinical and echocardiographic follow-up was
      undertaken in 400 consecutive patients who underwent mitral valvuloplasty from
      1987 to 1999. METHODS AND RESULTS: The main indications for surgery were
      degenerative (81.4%), endocarditis (7.1%), rheumatic (6.6%), ischemic (4.6%), and
      traumatic (0.3%) mitral valve disease. After excluding 6 paced patients and 1
      patient in nodal rhythm, we compared the outcomes of 152 patients in AF against
      241 patients in sinus rhythm. For patients in AF versus those in sinus rhythm,
      more AF patients were older (mean age 67.2+/-8.8 versus 61.9+/-11.8 years,
      respectively; P<0.001), more were assigned to a poorer New York Heart Association
      (NYHA) class (77.6% versus 66.0% in NYHA III/IV, respectively; P=0.01), and more
      demonstrated impaired ventricular function (78.9% versus 46.2% with moderate or
      severe impairment, respectively; P<0.001). For patients in AF versus those in
      sinus rhythm, there was no difference in 30-day mortality (2.0% versus 2.1%,
      respectively; P=0.95), repair failure (5.4% versus 3.6%, respectively; P=0.41),
      stroke (5.4% versus 2.2%, respectively; P=0.11), or endocarditis (2.3% versus
      0.9%, respectively; P=0.27) on follow-up at a median of 2.8 years (interquartile
      range 1.1 to 6.0). On echocardiography, the proportion of patients with mild
      regurgitation or worse was 13.3% (AF patients) versus 10.8% (patients in sinus
      rhythm) (P=0.70). Patients in AF versus those in sinus rhythm had lower survival
      at 3 years (83% versus 93%, respectively) and 5 years (73% versus 88%,
      respectively). Univariate analysis identified factors affecting survival as AF
      (P=0.002), age >70 years (P=0.041), and poor ventricular function (P<0.001).
      However, by use of a multivariate model, only poor ventricular function remained
      significant (P=0.01). CONCLUSIONS: AF does not affect early outcome or durability
      of mitral repair. The onset of AF may be indicative of disease progression
      because of its association with poor left ventricular function.

PMID- 11568032
TI  - Clinical and angiographic effects of chronic calcium channel blocker therapy
      continued beyond first postoperative year in patients with radial artery grafts:
      results of a prospective randomized investigation.
AB  - BACKGROUND: This study was conceived to elucidate the clinical and angiographic
      effects of chronic calcium channel blocker therapy (CCCBT) continued after the
      first postoperative year in patients in whom the radial artery (RA) was used for
      myocardial revascularization. METHODS AND RESULTS: Patients who received RA
      grafts at our institution and who at 1 year had no scintigraphic evidence of
      ischemia in the RA territory or angiographic evidence of RA malfunction (n=120)
      were randomly assigned to continue (n=63) or suspend (n=57) the CCCBT with
      diltiazem (120 mg/d). After 5 years, all patients were reassessed clinically and
      by stress myocardial scintigraphy, and 87 of them (45 from the continued group
      that continued CCCBT and 42 from the group that suspended CCCBT) were restudied
      angiographically. No differences regarding either the clinical and scintigraphic
      results or the RA angiographic status were demonstrated between the 2 groups.
      CONCLUSIONS: After the first postoperative year, the continuation of CCCBT does
      not affect RA graft patency or clinical and scintigraphic results.

PMID- 11568033
TI  - Does coronary artery bypass grafting alone correct moderate ischemic mitral
      regurgitation?
AB  - BACKGROUND: The optimal management of moderate (3+ on a scale of 0 to 4+)
      ischemic mitral regurgitation (MR) remains controversial. Some advocate CABG
      alone, whereas others favor concomitant mitral annuloplasty. To clarify the
      optimal management of these patients, we evaluated the early impact of isolated
      CABG on moderate ischemic MR. METHODS AND RESULTS: Between January 1992 and
      August 1999, 136 patients (54% male, mean age 70.5 years, mean New York Heart
      Association class 2.7, mean ejection fraction 38.1%) with a preoperative
      diagnosis of moderate ischemic MR, without leaflet prolapse or pathology,
      underwent isolated CABG. Thirty-eight (28%) of 136 patients had intraoperative
      transesophageal echocardiography (TEE) before CABG, and 68 (50%) had
      postoperative transthoracic echocardiography (TTE) within 6 weeks of surgery. The
      subgroups of patients undergoing intraoperative TEE and postoperative TTE had
      preoperative characteristics similar to the overall group. The 30-day operative
      mortality was 2.9% (). Intraoperative TEE downgraded the severity of MR to mild
      or less (0 to 2+) in 89% (). On postoperative TTE, 40% () continued to have at
      least moderate MR (3 to 4+), 51% () improved somewhat to mild (2+) MR, and only
      9% () had resolution of their MR (0 to 1+). The mean preoperative,
      intraoperative, and postoperative MR grades were 3.0+/-0.0, 1.4+/-1.0, and 2.3+/
      0.8, respectively (P<0.001). CONCLUSIONS: CABG alone for moderate ischemic MR
      leaves many patients with significant residual MR and may not be the optimal
      therapy for most patients. Intraoperative TEE may significantly underestimate the
      severity of ischemic MR. A preoperative diagnosis of moderate MR may warrant
      concomitant mitral annuloplasty.

PMID- 11568034
TI  - Coronary artery bypass with only in situ bilateral internal thoracic arteries and
      right gastroepiploic artery.
AB  - BACKGROUND: With the rapid advance of catheter intervention, the direction taken
      by surgeons is not only to make conventional CABG less invasive but also to
      pursue better long-term results by using more arterial conduits. METHODS AND
      RESULTS: Between July 1989 and April 2000, 239 patients (218 men, 21 women) with
      a mean age of 59.7 (range 39 to 79) years underwent CABG with exclusive use of
      both internal thoracic arteries (ITAs) and the right gastroepiploic artery
      (RGEA). ITA grafts were harvested by using the skeletonization technique. Most
      patients (96%) had either triple-vessel or left main disease. Fifty percent of
      the patients were diabetic, and 16 were being treated with insulin. The left
      ventricular ejection fraction was </=40% in 46 patients (19%). Eleven patients
      (5%) had chronic renal failure and were on hemodialysis. Follow-up was completed
      in 235 patients (98%). Postoperative follow-up averaged 43 (range 1 to 129)
      months. Sequential grafting was performed in 64 patients, and the mean number of
      anastomoses was 3.3. One patient (0.4%) died of mediastinitis on the 53rd
      postoperative day. Graft patency was confirmed angiographically in 230 patients
      (96%) 2 to 3 weeks after surgery. The patency rate was 97.1% for the left ITA,
      99.6% for the right ITA, and 95.5% for the RGEA. Five-year actuarial survival
      rate was 92.9%, and the cardiac death-free rate was 97.8%. CONCLUSIONS: Complete
      arterial grafting with both ITAs and RGEA was associated with minimal operative
      risk, a high early graft patency rate, and excellent long-term results.

PMID- 11568035
TI  - Sustained angina relief 5 years after transmyocardial laser revascularization
      with a CO(2) laser.
AB  - BACKGROUND: Although transmyocardial laser revascularization (TMR) has provided
      symptomatic relief of angina over the short term, the long-term efficacy of the
      procedure is unknown. Angina symptoms as assessed independently by angina class
      and the Seattle Angina Questionnaire (SAQ) were prospectively collected up to 7
      years after TMR. METHODS: Seventy-eight patients with severe angina not amenable
      to conventional revascularization were treated with a CO(2) laser. Their mean age
      was 61+/-10 years at the time of treatment. Preoperatively, 66% had unstable
      angina, 73% had had >/=1 myocardial infarction, 93% had undergone >/=1 CABG, 42%
      had >/=1 PTCA, 76% were in angina class IV, and 24% were in angina class III.
      Their average pre-TMR angina class was 3.7+/-0.4. RESULTS: After an average of 5
      years (and up to 7 years) of follow-up, the average angina class was
      significantly improved to 1.6+/-1 (P=0.0001). This was unchanged from the 1.5+/-1
      average angina class at 1 year postoperatively (P=NS). There was a marked
      redistribution according to angina class, with 81% of the patients in class II or
      better, and 17% of the patients had no angina 5 years after TMR. A decrease of
      >/=2 angina classes was considered significant, and by this criterion, 68% of the
      patients had successful long-term angina relief. The angina class results were
      further confirmed with the SAQ; 5-year SAQ scores revealed an average improvement
      of 170% over the baseline results. CONCLUSIONS: The long-term efficacy of TMR
      persists for >/=5 years. TMR with CO(2) laser as sole therapy for severe
      disabling angina provides significant long-term angina relief.

PMID- 11568036
TI  - Neuroprotective effect of mild hypothermia in patients undergoing coronary artery
      surgery with cardiopulmonary bypass: a randomized trial.
AB  - BACKGROUND: Neuropsychological deficits occur in 30% to 80% of patients
      undergoing heart surgery and are due in part to ischemic cerebral injury during
      cardiopulmonary bypass. We tested whether mild hypothermia, the most efficacious
      neuroprotective strategy found in laboratory studies, improved cognitive outcome
      in patients undergoing coronary artery surgery. METHODS AND RESULTS: Patients 60
      years or older scheduled for coronary artery surgery were enrolled. During
      cardiopulmonary bypass, patients were initially cooled to 32 degrees C then
      randomly assigned to rewarming to 37 degrees C (control) or 34 degrees C
      (hypothermic), with no further intraoperative warming. Testing was scheduled
      preoperatively and 1 week and 3 months postoperatively. Eleven tests were
      combined into 3 cognitive domains: memory, attention, and psychomotor speed and
      dexterity. A patient was classified as having a cognitive deficit if a decrease
      of >/=0.50 SD was realized in 1 or more domains. The incidence of cognitive
      deficits 1 week after surgery, which was the primary outcome, was 62% () in the
      control group and 48% () in the hypothermic group (relative risk 0.77, P=0.048).
      In the hypothermic group, the magnitude of deterioration in attention and in
      speed and dexterity was reduced by 55.6% (P=0.038) and 41.3% (P=0.042),
      respectively. At 3 months, the hypothermic group still performed better on one
      test of speed and dexterity (grooved pegboard). There was no difference in
      morbidity or mortality. CONCLUSIONS: Our findings support a neuroprotective
      effect of mild hypothermia in patients undergoing coronary artery surgery and
      should encourage physicians and perfusionists to pay careful attention to brain
      temperature during cardiopulmonary bypass.

PMID- 11568037
TI  - Waiting for cardiac surgery: results of a risk-stratified queuing process.
AB  - BACKGROUND: The Queen Elizabeth II Health Sciences Centre uses a weekly peer
      review conference of cardiovascular experts to prioritize each surgical case to 1
      of 4 queues with the use of standardized criteria of coronary anatomy, stress
      test result, and symptoms. We examined the hazard of waiting as well as the
      impact of waiting on surgical outcomes. METHODS AND RESULTS: Analysis was
      performed for 2102 consecutive patients queued for CABG, aortic valve
      replacement, or CABG+aortic valve replacement between January 1, 1998, and
      December 31, 1999. Among 1854 patients undergoing surgery, median waiting times
      on the respective queues were as follows: in-house urgent group, 8 days;
      semiurgent A group, 37 days; semiurgent B group, 64 days; and elective group, 113
      days. There were 13 deaths (12 cardiac) that occurred during the waiting period
      (0.7% of the patients). Of the 8.7% patients upgraded to a more urgent queue,
      86.1% required hospitalization before surgery. Although female sex was not
      associated with prolonged waiting time, it was predictive of urgent status
      (P=0.001). The incidence of postoperative complications was 25.0%, and operative
      mortality was 2.86%. Both were more frequent among patients undergoing surgery
      early (P=0.01); however, this difference was attributable to the in-house urgent
      queue. The median length of stay was 7 days for all patients and was not affected
      by waiting time. CONCLUSIONS: Death and upgrades while the patients were waiting
      tended to occur early in the queuing process, and prolonged waiting was not
      associated with worse surgical outcomes. The cost of reducing waiting times could
      in part be offset by prevention of hospital admissions among upgraded patients.

PMID- 11568038
TI  - Left mini-thoracotomy for beating heart bypass grafting: a safe alternative to
      high-risk intervention for selected grafting of the circumflex artery
      distribution.
AB  - BACKGROUND: Progression of disease and bypass graft attrition results in a
      population of patients who require repeated coronary interventions. Frequently,
      these patients have patent internal mammary artery grafts and require isolated
      intervention to the circumflex distribution. As an alternative to high-risk
      repeated sternotomy and conventional bypass surgery or catheter-based
      intervention, the circumflex marginal vessels may be approached by thoracotomy.
      We reviewed our experience in revascularizing the circumflex distribution with
      off-pump techniques via left mini-thoracotomy. METHODS AND RESULTS: Thirty-two
      patients underwent off-pump bypass grafting of the circumflex vessels via
      thoracotomy from December 1995 to April 2000. Twenty-seven patients presented
      with circumflex disease after having previous bypass grafting. Five patients, who
      presented with circumflex disease and either nondiseased or ungraftable disease
      in their other arteries, were revascularized as a primary procedure. There was no
      observed mortality. Seven patients (22%) required inotropes on leaving the
      operating room, and 3 patients (9.4%) received transfusion of packed red blood
      cells. There was 1 reoperation for bleeding and 1 patient with a postoperative
      neurological deficit. There were no perioperative myocardial infarctions. The
      average length of stay was 4.8 days from time of surgery to discharge.
      CONCLUSIONS: Off-pump grafting via thoracotomy provides a safe and effective
      alternative approach for patients requiring limited revascularization. Potential
      cardiac injury and danger to viable grafts from repeated sternotomy is minimized,
      and manipulation of the diseased ascending aorta is avoided. Morbidity, hospital
      length of stay, and cost are less than for conventional repeated coronary bypass
      surgery.

PMID- 11568039
TI  - Development of robotic enhanced endoscopic surgery for the treatment of coronary
      artery disease.
AB  - BACKGROUND: The introduction of robotic enhanced surgery demanded stepwise
      development of performed procedures on the basis of growing experience of the
      operating team. METHODS AND RESULTS: Between May 1999 and January 2001, this new
      wrist-enhanced instrumentation was used in 201 patients (156 men and 45 women,
      median age 64+/-10.5 years, left ventricular ejection fraction 68+/-12.4%).
      During the development of robotic enhanced CABG, the patients were divided into 3
      groups. Group A (n=156) consisted of patients in whom the robotic system was used
      to harvesting the left or right internal mammary artery, or both, whereas the
      anastomoses were performed directly through a small chest incision. In group B
      (n=37), the harvest of the internal mammary arteries and the coronary anastomoses
      were performed totally endoscopically. In a third early group C, patient (n=8)
      were treated with robotic enhanced CABG via a median sternotomy already
      preoperatively planned, whereas gradual step-by-step application of robotic
      instrumentation and its feasibility were assessed. The survival rate was 99.4%.
      One patient (0.6%) died due to pneumonia on postoperative day 16. Conversion rate
      to median sternotomy was 5%. The left and right internal mammary artery conduits
      could be successfully harvested in 98% and 100%, respectively. The time of
      dissection of the left internal mammary artery could be significantly reduced
      alone by increasing experience. All patients were discharged from the hospital
      after a mean of 7 days. In 9 patients (4.5%), bleeding required reexploration.
      CONCLUSIONS: The introduction of this new surgical tool enables the development
      of new endoscopic procedures. Our results gained during the development of
      robotic enhanced CABG motivate us to establish a set standard for the totally
      endoscopic treatment of patients with 1-vessel coronary artery disease.

PMID- 11568040
TI  - Autologous endothelialized vein allograft: a solution in the search for small
      caliber grafts in coronary artery bypass graft operations.
AB  - BACKGROUND: Early graft failure after the use of less satisfactory autologous
      grafts (30% of all vein grafts) is caused primarily by the following problems:
      (1) suitable autologous transplants are limited; (2) biotechnology has not yet
      been able to produce reliable graft substitutes that are legally and ethically
      approved; and (3) current prosthetic materials are prothrombotic. To overcome
      these problems, we developed an easily accessible, quality-controlled graft.
      METHODS AND RESULTS: Human autologous venous endothelial cells (HAVECs) were
      isolated from short segments of peripheral veins unsuitable for bypass grafting.
      After mechanical deendothelialization of cryopreserved allograft veins (CAVs) and
      precoating with recipient autologous serum, these homologous cells were seeded by
      use of a rotating device. Growth of a confluent HAVEC layer within 1 week in a
      special incubator was observed. After histological and mechanical tests, 12
      patients received 15 grafts in total. Bypass operation was followed by clinical
      and angiographic follow-up. Production period was 22+/-8 days. HAVEC-coated CAVs
      showed normal connective tissue wall structure and a tight endothelial monolayer
      (burst pressure >2000 mm Hg). To date, 12 CABG patients lacking suitable
      autologous graft material have been treated. One patient died of a cause
      unrelated to the grafts, which were found morphologically normal and patent
      during autopsy. Of 15 grafts, 2 were occluded at the first angiographic follow
      up. The oldest graft has now been in place for approximately 3 years. Immune
      suppression was not administered. CONCLUSIONS: At present, autologous
      endothelialized CAVs present good alternative small-caliber grafts for patients
      lacking suitable autologous vessels.

PMID- 11568041
TI  - Transmyocardial laser revascularization remodels the intrinsic cardiac nervous
      system in a chronic setting.
AB  - BACKGROUND: Prospective trials have demonstrated that transmyocardial laser
      revascularization (TMLR) imparts symptomatic relief to patients with refractory
      angina. Because peak clinical effectiveness of TMLR is usually delayed by several
      months, it has been proposed that ventricular denervation is one mechanism
      whereby TMLR imparts symptomatic relief. We have demonstrated that TMLR does not
      denervate the heart in the acute setting, nor does it modify the intrinsic
      cardiac nervous system (ICNS) in the acute setting. However, the long-term
      effects of TMLR on the ICNS remain unknown. METHODS AND RESULTS: A
      holmium:yttrium-aluminum-garnet laser created 20 channels through the
      anterolateral left ventricular free wall of 10 dogs. Four weeks later, the
      function of cardiac sensory inputs to the ICNS was studied by applying
      veratridine (7.5 micromol/L) to ventricular sensory fields. Chronotropic and
      inotropic responses elicited by cardiac sympathetic or parasympathetic efferent
      neurons stimulated electrically (10 Hz, 4 V, 4 ms) or chemically (nicotine 5 to
      20 microgram/kg IV) were also assessed. Chemical activation of epicardial sensory
      neurites with veratridine elicited expected ICNS excitatory responses. Electrical
      stimulation of sympathetic and parasympathetic efferent neurons induced expected
      altered cardiac responses. In contrast, the responsiveness of the ICNS to
      systemically administered nicotine was obtunded. CONCLUSIONS: Although chronic
      TMLR does not affect cardiac afferent or extracardiac efferent neuronal function,
      it does "remodel" the ICNS so that its responsiveness to a known potent chemical
      agonist (ie, nicotine) becomes obtunded. Remodeling of the ICNS may account in
      part for the delayed symptomatic relief that TMLR imparts to patients with
      refractory angina.

PMID- 11568042
TI  - Late outcome after arterial switch operation for transposition of the great
      arteries.
AB  - BACKGROUND: Early and midterm results of the arterial switch operation (ASO) in
      transposition of the great arteries (TGA) are good, but late outcome data in
      large populations are still few. METHODS AND RESULTS: Twelve hundred patients had
      an ASO for TGA between 1982 and 1999, with prospective follow-up of 1095
      survivors. Outcome measures included late death, reoperation, aortic
      insufficiency (AI), pulmonary stenosis (PS), and coronary anomaly. Median follow
      up was 4.9 years (range 0.5 to 17 years). Late death occurred in 32 patients;
      survival was 88% at both 10 and 15 years. The hazard function for death declined
      rapidly, with no deaths after 5 years. Late mortality was correlated with
      reintervention and major events in the intensive care unit. Reoperation was
      performed in 103 patients, more often in complex TGA; the cause was mainly PS.
      Freedom from reintervention was 82% at 10 and 15 years, with a hazard function
      that declined rapidly but slowly increased after 3 years. At the last follow-up,
      PS was present in 3.9% of patients, and grade II or more AI was present in 3.2%,
      with a cumulative incidence of 9% at 15 years. Among the 278 patients who had a
      coronary arteriography, 8% had coronary lesions. Normal left ventricle and sinus
      rhythm were seen in 96.4% and 98.1%, respectively. CONCLUSIONS: Fifteen years
      after ASO, late mortality was low, with no deaths after 5 years; reoperation,
      mainly owing to PS, occurred throughout the follow-up. AI and coronary
      obstruction are rare but warrant further follow-up. Good left ventricular
      function and sinus rhythm are maintained.

PMID- 11568043
TI  - Neurodevelopmental outcomes in children after the fontan operation.
AB  - BACKGROUND: Previous studies of patients after the Fontan operation have reported
      IQ scores lower than population norms. In the past decade, changes have occurred
      both in surgical methods used and in the patient population undergoing Fontan
      palliation. The present study examined the impact of these changes on
      neurodevelopmental outcomes after Fontan. METHODS AND RESULTS: Neuropsychological
      tests were administered to 27 five-year-old children after Fontan. Mean age at
      repair was 2 years 4 months. The present sample was compared with an earlier
      Fontan group (EFG) of 133 patients who underwent surgery in the 1970s and 1980s.
      Mean age at repair for the EFG was 7 years 3 months. Compared with EFG, the
      present study sample was younger at Fontan (P=0.0001) and more likely to have
      undergone a Norwood procedure (P=0.02), a pre-Fontan bidirectional cavopulmonary
      anastomosis (P<0.001), and Fontan fenestration (P=0.001). Although mean full
      scale, verbal, and performance IQ scores were within 1 SD (15 points) of the
      population mean of 100 (93+/-16, 95+/-15, and 91+/-17, respectively), mean full
      scale and performance IQ scores were significantly lower than this population
      mean (P=0.03 and P=0.01, respectively). CONCLUSIONS: Compared with a historical
      cohort of Fontan patients from this institution, a staged approach to Fontan
      earlier in life is not detrimental to neurodevelopmental outcome.
      Neurodevelopmental outcomes in children after Fontan are in the normal range, but
      performance remains lower than the general population.

PMID- 11568044
TI  - Posterior pericardial ascending-to-descending aortic bypass: an alternative
      surgical approach for complex coarctation of the aorta.
AB  - BACKGROUND: Coarctation of the aorta is commonly associated with recoarctation or
      additional cardiovascular disorders that require intervention. The best surgical
      approach in such patients is uncertain. Ascending-to-descending aortic bypass
      graft via the posterior pericardium (CoA bypass) allows simultaneous intracardiac
      repair or an alternative approach for the patient with complex coarctation.
      METHODS AND RESULTS: Between 1985 and 2000, 18 patients (13 males and 5 females,
      mean age 43+/-13 years) with coarctation of the aorta underwent CoA bypass
      through median sternotomy. Before operation, average New York Heart Association
      class was II (range I to IV), and 15 patients (83%) had systemic hypertension.
      One or more previous cardiovascular operations had been performed in 12 patients
      (67%); 10 patients had >/=1 prior coarctation repair. Two patients had prior
      noncoarctation cardiovascular surgery. Concomitant procedures performed in 14
      patients (78%) included the following: aortic valve replacement in 9; coronary
      artery bypass surgery in 3; mitral valve repair in 2; and septal myectomy, mitral
      valve replacement, aortoplasty, subaortic stenosis resection, ventricular septal
      defect closure, and ascending aorta replacement in 1 patient each. All patients
      survived the operation and were alive with patent CoA bypass at a mean follow-up
      of 45 months. No graft-related complications occurred, and there were no
      instances of stroke or paraplegia. Systolic blood pressure fell from 159 mm Hg
      before surgery to 125 mm Hg after surgery. CONCLUSIONS: CoA bypass via median
      sternotomy can be performed with low morbidity and mortality. Although management
      must be individualized, extra-anatomic CoA bypass via the posterior pericardium
      is an excellent single-stage approach for patients with complex coarctation or
      recoarctation and concomitant cardiovascular disorders.

PMID- 11568045
TI  - General health status of children with D-transposition of the great arteries
      after the arterial switch operation.
AB  - BACKGROUND: To study the long-term impact on general health status of D
      transposition of the great arteries (D-TGA) after the arterial switch operation
      (ASO) during infancy, we asked parents to complete the Child Health
      Questionnaire, Parent Form-50 when their children were 8 years old. METHODS AND
      RESULTS: Of 160 eligible patients, questionnaires were completed for 155 subjects
      (96%). Median age at surgery was 6 days (range 1 to 67 days), and median age at
      completion of the Child Health Questionnaire was 8.1 years (7.6 to 10.0 years).
      Subsequent to questionnaire completion, children underwent psychometric testing.
      Mean Physical Health Summary and Psychosocial Summary scores were 54.0+/-6.1 and
      49.7+/-9.9, respectively, which were similar to those of normal subjects.
      Compared with the normative sample, parents of D-TGA patients reported more
      problems with attention, learning, and speech, as well as greater frequency of
      developmental delay (P<0.001 for each). Worse Psychosocial Summary scores were
      significantly associated with lower full-scale IQ (P=0.001) and lower achievement
      in reading (P=0.005) and math (P=0.007). Worse Physical Health Summary scores
      were associated with longer hospital stay after the ASO (P=0.02). General health
      status scores were not significantly related to presence of ventricular septal
      defect, age at surgery, perfusion variables during the ASO, sex, or history of
      cardiac reoperation. CONCLUSIONS: At age 8 years, children with D-TGA after ASO
      have an overall physical and psychosocial health status similar to that of the
      general population. Lower IQ and academic achievement are associated with worse
      psychosocial health status, whereas longer hospital course after initial surgery
      is associated with worse physical health status.

PMID- 11568046
TI  - Long-term survival after mitral valve replacement in children aged <5 years: a
      multi-institutional study.
AB  - BACKGROUND: Short- and long-term outcomes after prosthetic mitral valve
      replacement (MVR) in children aged <5 years are ill-defined and generally
      perceived as poor. The experience of the Pediatric Cardiac Care Consortium (45
      centers, 1982 to 1999) was reviewed. METHODS AND RESULTS: MVR was performed 176
      times on 139 patients. Median follow-up was 6.2 years (range 0 to 20 years, 96%
      complete). Age at initial MVR was 1.9+/-1.4 years. Complications after initial
      MVR included heart block requiring pacemaker (16%), endocarditis (6%), thrombosis
      (3%), and stroke (2%). Patient survival was as follows: 1 year, 79%; 5 years,
      75%; and 10 years, 74%. The majority of deaths occurred early after initial MVR,
      with little late attrition despite repeat MVR and chronic anticoagulation. Among
      survivors, the 5-year freedom from reoperation was 81%. Age-adjusted
      multivariable predictors of death include the presence of complete
      atrioventricular canal (hazard ratio 4.76, 95% CI 1.59 to 14.30), Shone's
      syndrome (hazard ratio 3.68, 95% CI 1.14 to 11.89), and increased ratio of
      prosthetic valve size to patient weight (relative risk 1.77 per mm/kg increment,
      95% CI 1.06 to 2.97). Age- and diagnosis-adjusted prosthetic size/weight ratios
      predicted a 1-year survival of 91% for size/weight ratio 2, 79% for size/weight
      ratio 3, 61% for size/weight ratio 4, and 37% for size/weight ratio 5.
      CONCLUSIONS: Early mortality after MVR can be predicted on the basis of diagnosis
      and the size/weight ratio. Late mortality is low. These data can assist in
      choosing between MVR and alternative palliative strategies.

PMID- 11568047
TI  - Factors related to pleural effusions after Fontan procedure in the era of
      fenestration.
AB  - BACKGROUND: Significant pleural effusions after the Fontan operation prolong
      hospital stay, may increase the risk of infection, and may necessitate a
      pleurodesis procedure. METHODS AND RESULTS: From February 1991 to April 2000, 98
      consecutive patients under the age of 18 years underwent the fenestrated Fontan
      procedure at Children's Hospital of Wisconsin. Ninety-four patients who survived
      at least 30 days after surgery were retrospectively evaluated for the following
      factors: age, ventricular morphology (right single ventricle, left single
      ventricle [RV/LV]), fenestration open (FO) or closed (FC) at end of operation,
      intracardiac Fontan (IF) or extracardiac Fontan (EF), days with chest tube output
      per day >5, 10, and/or 20 mL. kg(-1). d(-1) (CTO5, CTO10, and CTO20,
      respectively), need for pleurodesis, length of hospital stay (LOS), operation
      during winter respiratory viral season of November through March (ReVS+, ReVS-),
      and pre-Fontan mean pulmonary artery pressure (PAP) and pulmonary vascular
      resistance (PVR). In univariate analysis, the ReVS+ patients had prolonged LOS,
      greater chest tube output, and more pleurodesis (P<0.05), and PAP was related to
      CTO5 and CTO10 but not to CTO20 or LOS. No significant differences were found in
      LOS, CTO5, CTO10, CTO20, and need for pleurodesis between patients in RV/LV,
      FO/FC, IF/EF, or PVR groups. Patients <4 years of age had more instances of CTO20
      (P<0.05). When we used ordinary least squares regression analysis with age, FO or
      FC, RV or LV, PAP, and ReVS+ or ReVS- to predict each of CTO5, CTO10, CTO20, and
      LOS, only ReVS+ or ReVS- and age were statistically significant in all models.
      CONCLUSIONS: Use of the Fontan procedure during the respiratory viral season
      appeared to be related to significant, prolonged pleural effusions and longer
      hospitalizations.

PMID- 11568048
TI  - Are outcomes of surgical versus transcatheter balloon valvotomy equivalent in
      neonatal critical aortic stenosis?
AB  - BACKGROUND: For neonates with critical aortic valve stenosis who are selected for
      biventricular repair, valvotomy can be achieved surgically (SAV) or by
      transcatheter balloon dilation (BAV). METHODS AND RESULTS: Data regarding 110
      neonates with critical aortic valve stenosis were evaluated in a study by the
      Congenital Heart Surgeons Society from 1994 to 1999. Reduced left ventricular
      function was present in 46% of neonates. The initial procedure was SAV in 28
      patients and BAV in 82 patients. Mean percent reduction in systolic gradient was
      significantly greater with BAV (65+/-17%) than SAV (41+/-32%; P<0.001). Higher
      residual median gradients were present in the SAV versus BAV group (36 mm Hg
      [range, 10 to 85 mm Hg] versus 20 mm Hg [0 to 85 mm Hg], P<0.001). Important
      aortic regurgitation was more often present after BAV (18%) than SAV (3%;
      P=0.07). Time-related survival after valvotomy was 82% at 1 month and 72% at 5
      years, with no significant difference for SAV versus BAV, even after adjustment
      for differences in patient and disease characteristics. Independent risk factors
      for mortality were mechanical ventilation before valvotomy, smaller aortic valve
      annulus (z score), smaller aortic diameter at the sinotubular junction (z score),
      and a smaller subaortic region. A second procedure was performed in 46 survivors.
      Estimates for freedom from reintervention were 91% at 1 month and 48% at 5 years
      after the initial valvotomy and did not differ significantly between groups.
      CONCLUSIONS: SAV and BAV for neonatal critical aortic stenosis have similar
      outcomes. There is a greater likelihood of important aortic regurgitation with
      BAV and of residual stenosis with SAV.

PMID- 11568049
TI  - Impact of inspired gas mixtures on preoperative infants with hypoplastic left
      heart syndrome during controlled ventilation.
AB  - BACKGROUND: Management strategies for preoperative infants with hypoplastic left
      heart syndrome (HLHS) include increased inspired nitrogen (hypoxia) and increased
      inspired carbon dioxide (hypercarbia). There are no studies directly comparing
      these 2 therapies in humans. This study compares the impact of hypoxia versus
      hypercarbia on oxygen delivery, under conditions of fixed minute ventilation.
      METHODS AND RESULTS: Ten anesthetized and paralyzed preoperative infants with
      HLHS were evaluated in a prospective, randomized, crossover trial comparing
      hypoxia (17% FIO(2)) with hypercarbia (2.7% FICO(2)). Each patient was treated in
      a random order (10 minutes per condition) with a recovery period (15 to 20
      minutes) in room air. Arterial (SaO(2)) and superior vena caval (SvO(2)) co
      oximetry and cerebral oxygen saturation (ScO(2)) measurements were made at the
      end of each condition and recovery period. ScO(2) was measured by near infrared
      spectroscopy. Hypoxia significantly decreased both SaO(2) (-5.2+/-1.1%, P=0.0014)
      and SvO(2) (-5.6+/-1.7%, P=0.009) compared with baseline, but arteriovenous
      oxygen saturation (AVO(2)) difference (SaO(2)-SvO(2)) and ScO(2) remained
      unchanged. Hypercarbia decreased SaO(2) (-2.6+/-0.6%, P=0.002) compared with
      baseline but increased both ScO(2) (9.6+/-1.8%, P=0.0001) and SvO(2) (6+/-2.2%,
      P=0.022) and narrowed the AVO(2) difference (-8.5+/-2.3%, P=0.005). Both hypoxia
      and hypercarbia decreased the balance between pulmonary and systemic blood flow
      (Qp:Qs) compared with baseline. CONCLUSIONS: In preoperative infants with HLHS,
      under conditions of anesthesia and paralysis, although Qp:Qs falls in both
      conditions, oxygen delivery is unchanged during hypoxia and increased during
      hypercarbia. These data cannot differentiate cerebral from systemic oxygen
      delivery.

PMID- 11568050
TI  - Vascular dysfunction after repair of coarctation of the aorta: impact of early
      surgery.
AB  - BACKGROUND: Patients with repaired coarctation are at increased risk of
      hypertension and cardiovascular disease despite successful repair. We studied the
      function of conduit arteries in upper and lower limbs of patients late after
      successful coarctation repair and its relation to age at surgery. METHODS AND
      RESULTS: Flow-mediated dilatation (FMD) and the dilatation after sublingual
      nitroglycerin (NTG, 25 microgram) were measured by using high-resolution
      ultrasound in the brachial artery in 64 coarctation patients (44 males and 20
      females, aged 19+/-10 years; median age at operation 4 months) and 45 control
      subjects (28 males and 17 females, aged 19+/-10 years) and in the posterior
      tibial artery in 37 patients and 22 control subjects. Arterial stiffness was
      determined by pulse-wave velocity (PWV) of the brachioradial and femoral-dorsalis
      pedis tracts. Patients, compared with control subjects, had lower brachial FMD
      (7.16+/-3.4% versus 8.62+/-2.3%, respectively; P=0.02) and NTG (11.46+/-4.3%
      versus 13.21+/-4.6%, respectively; P=0.046) and higher brachioradial PWV (9.17+/
      3.1 versus 8.06+/-1.9 m/s, respectively; P=0.05). In contrast, posterior tibial
      FMD, NTG, and lower limb PWV were comparable. Age (months) at the time of repair
      was related to brachioradial PWV (r=0.42, P=0.002) but not to brachial FMD or
      NTG. CONCLUSIONS: Patients with repaired aortic coarctation have impaired conduit
      artery function, with abnormal responses to flow and NTG, and increased vascular
      stiffness confined to the upper part of the body. Early repair is associated with
      preserved elastic properties of conduit arteries, but reduced reactivity remains.

PMID- 11568051
TI  - Survival benefit of the implantable cardioverter-defibrillator in patients on the
      waiting list for cardiac transplantation.
AB  - BACKGROUND: The implantable cardioverter-defibrillator (ICD) effectively reduces
      sudden cardiac death in patients with severe LV dysfunction. Effect of ICD
      therapy on total mortality in patients on the waiting list for cardiac
      transplantation is still uncertain. METHODS AND RESULTS: We retrospectively
      analyzed 854 unselected consecutive patients (ICD therapy, n=102; 11.9%) on the
      waiting list for cardiac transplantation between January 1992 and March 2000.
      Actuarial 12-month total mortality rate on the waiting list was 24.2%; sudden
      cardiac death was the predominant mode of death (66.7% of total deaths). Kaplan
      Meier analysis revealed improved survival for ICD (total mortality, 13.2%)
      compared with non-ICD (total mortality, 25.8%) patients (log rank, P=0.03). No
      event of sudden death occurred in ICD patients, whereas in non-ICD patients, 12
      month sudden death rate was 20.1% (P=0.0001). Nonsudden death rates did not
      differ between ICD and non-ICD patients (P=0.16). A Cox proportional hazards
      model demonstrated that absence of an ICD was a powerful independent predictor of
      total mortality (P=0.02; relative risk, 2.22; 95% confidence interval, 1.16 to
      4.17) and sudden cardiac death (P<0.0001; infinite relative risk) on the waiting
      list. CONCLUSIONS: ICD therapy, because it prevents sudden cardiac death,
      significantly improves survival on the waiting list for cardiac transplantation.
      The present study supports the use of ICDs as a bridge to transplantation in
      patients who are at risk of sudden cardiac death. Prospective randomized trials
      are needed to evaluate the potential benefit of prophylactic ICD therapy as a
      bridge to transplantation in all patients on cardiac transplant waiting lists.

PMID- 11568052
TI  - Increased prevalence of autoimmune phenomena and greater risk for alloreactivity
      in female heart transplant recipients.
AB  - BACKGROUND: The influence of sex on alloreactivity and graft outcome after heart
      transplantation was evaluated. METHODS AND RESULTS: A retrospective review of 520
      consecutive recipients of a primary cardiac allograft between 1992 and 2000 at a
      single center was performed. The influence of sex on alloreactivity, acute
      rejection, transplant-related coronary artery disease, and survival was
      determined. Statistical methods included logistic regression analysis and Kaplan
      Meier actuarial survival analysis. Female recipients had an increased prevalence
      before transplant of idiopathic cardiomyopathy, antinuclear antibodies, and HLA
      B8, DR3 haplotypes. After transplant, female sex predicted shorter duration to a
      first rejection, higher cumulative rejection frequency, and earlier
      posttransplant production of anti-HLA antibodies. Female recipients had higher
      early mortality rates (<6 months) that were due to infection. Fatal infections
      correlated with 2-fold higher cyclosporine levels in female recipients. However,
      the incidence of transplant-related coronary artery disease developing beyond 1
      year after transplant was lower in female than in male recipients. CONCLUSIONS:
      Females undergoing cardiac transplantation are more likely to manifest features
      of an underlying autoimmune state. This may predispose to a higher posttransplant
      risk of allograft rejection and requirement for increased immunosuppression.
      Earlier diagnosis and management of alloreactivity in female recipients before
      development of acute rejection and the use of more focused and less globally
      immunosuppressive agents during established rejections may have a significant
      effect on the clinical outcome of female cardiac allograft recipients.

PMID- 11568053
TI  - Reliability of tissue Doppler wall motion monitoring after heart transplantation
      for replacement of invasive routine screenings by optimally timed cardiac
      biopsies and catheterizations.
AB  - BACKGROUND: Invasive screenings at predefined time intervals for acute rejection
      and transplant coronary artery disease (TxCAD) are standard procedures. However,
      cardiac biopsies and catheterizations are distressing and risky for the patients
      and are also costly. We assessed the reliability of pulsed-wave tissue Doppler
      imaging (PW-TDI) for the timing of invasive examinations in heart recipients in
      an attempt to avoid unnecessary endomyocardial biopsies (EMBs) and
      catheterizations. METHODS AND RESULTS: PW-TDI obtained at the basal left
      ventricular posterior wall before 408 EMBs and 293 catheterizations was tested
      for its diagnostic value regarding rejection and TxCAD with the use of
      International Society of Heart and Lung Transplantation biopsy grading, coronary
      angiography, and intravascular ultrasound as standards. Early diastolic peak wall
      motion velocity and relaxation time showed high sensitivities for clinically
      relevant rejection diagnosis (90.0% and 93.3%, respectively). The negative and
      positive predictive values for rejection of diastolic parameter changes appeared
      high enough (up to 96% and 92%, respectively) to allow a reliable noninvasive PW
      TDI monitoring with efficiently timed, instead of routinely scheduled, EMBs. At
      definite cutoff values for systolic parameters, the probability for TxCAD reached
      92% to 97%. The Fisher classification functions allowed TxCAD exclusion with 80%
      probability. CONCLUSIONS: Without diastolic parameter changes, acute rejection
      can be practically excluded, and serial PW-TDI can save patients from routine
      EMBs. The high specificity and negative predictive value for TxCAD of reduced
      systolic peak velocities and extended systolic time allow optimized timed
      catheterizations. Peak systolic velocity and systolic time allow diagnostic
      classifications that enable patients without known TxCAD but with high risk for
      catheterization to be spared routine angiographies.

PMID- 11568054
TI  - Procalcitonin, a donor-specific predictor of early graft failure-related
      mortality after heart transplantation.
AB  - BACKGROUND: To date, donor-specific markers to predict outcome after heart
      transplantation (HTx) are unknown. Increased procalcitonin (PCT) levels have been
      found in infectious inflammation with systemic reactions and/or poor organ
      perfusion but have not been studied in heart donors. We evaluated PCT as a
      predictor of early graft failure-related mortality after HTx. METHODS AND
      RESULTS: PCT and C-reactive protein (CRP) serum concentrations were measured in
      samples collected immediately before pericardium opening from 81 consecutive
      brain-dead multiple-organ donors. Donors for high-urgency-status recipients (n=2)
      were excluded from analysis. The remaining donors were retrospectively divided
      into 2 groups: donors for recipients who died within 30 days after HTx, after an
      early graft failure (group II, n=8), and all other donors (group I, n=71). No
      differences in donor and recipient demographic characteristics were found between
      groups. Areas under the receiver operating characteristic curves for graft
      failure-related mortality were 0.71 for PCT and 0.64 for CRP. A PCT value >2
      ng/mL as a predictor of graft failure-related mortality had a specificity of
      95.8% and sensitivity of 50.0%. The odds ratio for graft failure-related
      mortality for recipients of hearts from donors with PCT levels >2 ng/mL was 22.7
      (unadjusted, 95% CI 3.7 to 137.8, P=0.0007) and 43.8 (after adjustment for
      prespecified potential confounders, 95% CI 1.4 to 1361.0, P=0.031). CONCLUSIONS:
      A PCT level >2 ng/mL in a cardiac donor at the time of explantation appears to
      predict early graft failure-related mortality.

PMID- 11568055
TI  - Evidence of functional myocardial ischemia associated with myocardial dysfunction
      in brain-dead pigs.
AB  - BACKGROUND: Cardiac dysfunction after brain death has been documented, but its
      mechanisms remain unclear. Myocardial ischemia has been suggested as a possible
      cause. The aim of the present study was to investigate the existence of an
      imbalance between myocardial oxygen delivery and demand as a possible cause of
      myocardial dysfunction in brain-dead pigs. METHODS AND RESULTS: Interstitial
      myocardial lactate and adenosine concentrations were assessed with cardiac
      microdialysis in 2 groups of animals: brain-dead pigs (n=7) and brain-dead pigs
      treated with labetalol (10+/-3 mg/kg) (n=7). Heart rate (HR), left ventricular
      (LV) dP/dt(max), rate-pressure product (RPP), cardiac output (CO), and left
      anterior descending coronary artery blood flow (QLAD) were continuously
      monitored. Brain-dead pigs exhibited a transient significant increase in HR, LV
      dP/dt(max), RPP, and CO and a limited increase in QLAD. This resulted in
      functional myocardial ischemia attested to by the significantly increased
      adenosine and lactate microdialysate concentrations. In brain-dead pigs treated
      with labetalol, there was a moderate increase in HR, QLAD, and adenosine
      microdialysate concentrations; LV dP/dt(max), RPP, CO, and myocardial lactate
      concentrations remained stable, confirming the preservation of aerobic
      metabolism. CONCLUSIONS: Brain death was associated with an increase in
      myocardial interstitial adenosine and lactate concentrations, as well as with
      myocardial dysfunction; all were attenuated by labetalol, suggesting an imbalance
      between oxygen consumption and oxygen delivery as a possible cause of myocardial
      dysfunction after brain death.

PMID- 11568056
TI  - Upregulation of Bcl-2 through caspase-3 inhibition ameliorates
      ischemia/reperfusion injury in rat cardiac allografts.
AB  - BACKGROUND: Oxidative stress after ischemia/reperfusion of cardiac allografts
      leads to cytokine production. Bcl-2, an inhibitor of apoptosis, also has strong
      antioxidant properties. Caspase-3 is known to cleave bcl-2. This study tests the
      hypothesis that bcl-2 is downregulated while tumor necrosis factor-alpha (TNF
      alpha) levels increase after cardiac transplantation. Furthermore, the use of
      caspase-3 inhibition was investigated as a strategy for preserving myocardial bcl
      2 and mitochondrial cytochrome c after transplantation. METHODS AND RESULTS: PVG
      to-ACI rat heterotopic cardiac transplantations were performed in 4 groups
      designed with 30 minutes' ischemia and 4 or 8 hours of reperfusion (n=4 per
      group). Treatment consisted of DEVD-CHO 500 microgram IP per animal to donor and
      recipient 2 hours before transplantation and 250 microgram IC into allograft.
      Controls were treated with saline. Grafts were analyzed by reverse transcription
      polymerase chain reaction for bcl-2 mRNA, by ELISA for TNF-alpha, for
      myeloperoxidase activity, and by Western blot for cytochrome c. In untreated
      groups, bcl-2 mRNA decreased significantly over time, whereas TNF-alpha increased
      significantly at 4 hours (P=0.003) and returned to baseline after 8 hours'
      reperfusion (P=NS compared with normal hearts). Treatment with caspase-3
      inhibitor showed significant upregulation of bcl-2 mRNA expression after 4 and 8
      hours of reperfusion (P<0.001 versus control), with a concomitant decrease in TNF
      alpha to baseline levels. Myeloperoxidase activity in all groups was no different
      from that of normal hearts. Mitochondrial cytochrome c release increased in both
      control and treatment groups. CONCLUSIONS: Bcl-2 is actively downregulated and
      TNF-alpha is upregulated in this model of cardiac allograft ischemia/reperfusion.
      Furthermore, the caspase-3 pathway is linked to this process, and blockade of
      caspase-3 can ameliorate reperfusion injury by upregulating bcl-2 and inhibiting
      TNF-alpha without affecting cytochrome c release.

PMID- 11568057
TI  - Cell transplantation for the treatment of acute myocardial infarction using
      vascular endothelial growth factor-expressing skeletal myoblasts.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a promising reagent for
      inducing myocardial angiogenesis. Skeletal myoblast transplantation has been
      shown to improve cardiac function in chronic heart failure models by regenerating
      muscle. We hypothesized that transplantation of VEGF-expressing myoblasts could
      effectively treat acute myocardial infarction by providing VEGF-induced
      cardioprotection through vasodilatation in the early phase, followed by
      angiogenesis effects in salvaging ischemic host myocardium combined with the
      functional benefits of newly formed, skeletal myoblast-derived muscle in the
      later phase. METHODS AND RESULTS: Primary rat skeletal myoblasts were transfected
      with the human VEGF(165) gene using hemagglutinating virus of Japan-liposome with
      >95% transfection efficiency. Four million of these myoblasts (VEGF group),
      control-transfected myoblasts (control group), or medium only (medium group) was
      injected into syngeneic rat hearts 1 hour after left coronary artery occlusion.
      Myocardial VEGF-expression increased for 2 weeks in the VEGF group, resulting in
      enhanced angiogenesis without the formation of tumors. Grafted myoblasts had
      differentiated into multinucleated myotubes within host myocardium. Infarct size
      (33.3+/-1.4%, 38.1+/-1.4%, and 43.7+/-1.6% for VEGF, control, and medium groups,
      respectively; P=0.0005) was significantly reduced with VEGF treatment, and
      cardiac function improved in the VEGF group (maximum dP/dt: 4072.0+/-93.6,
      3772.5+/-101.1, and 3482.5+/-90.6 mm Hg/s in the 3 groups, respectively;
      P=0.0011; minimum dP/dt: -504.2+/-68.5, -2311.3+/-57.0, and -2124.0+/-57.9 mm
      Hg/s, respectively; P=0.0008). CONCLUSIONS: This combined strategy of cell
      transplantation with gene therapy could be of importance for the treatment of
      acute myocardial infarction.

PMID- 11568058
TI  - Intracoronary infusion of skeletal myoblasts improves cardiac function in
      doxorubicin-induced heart failure.
AB  - BACKGROUND: Skeletal myoblast transplantation is promising for the treatment of
      end-stage heart failure. Direct intramyocardial injection is useful for local
      cell delivery but may not be effective in global dissemination of cells into the
      heart, which would be advantageous in treating generalized cardiac dysfunction as
      in dilated cardiomyopathy. We hypothesized that intracoronary infusion of
      myoblasts would disseminate cells more effectively, leading to functional
      improvement in global heart failure. METHODS AND RESULTS: Heart failure was
      induced by the intraperitoneal administration of doxorubicin (total dose 15
      mg/kg) in rat. One million primary skeletal myoblasts were then infused via the
      coronary arteries of an excised, failing doxorubicin-treated heart. After
      incubation under increased intracoronary pressure, the hearts were subsequently
      transplanted into syngeneic recipients. For the control group, doxorubicin
      treated hearts were infused with medium only and transplanted. Four weeks after
      transplantation, Langendorff perfusion demonstrated that both maximum dP/dt
      (2797.6+/-103.3 versus 2326.9+/-133.1 mm Hg/s, P=0.01) and minimum dP/dt (
      2067.4+/-88.1 versus -1718.8+/-91.3 mm Hg/s, P=0.02) were improved in myoblast
      transplanted hearts compared with medium-infused hearts. This was associated with
      a sharper slope of the left ventricular developed pressure-volume curve and a
      reduced slope of the end-diastolic pressure-volume relation in the myoblast
      transplanted hearts. Immunohistochemistry for skeletal myosin heavy chain showed
      that globally disseminated myoblasts had survived and differentiated into
      multinucleated myotubes that had aligned with the cardiac fiber axis within host
      myocardium. No significant myocardial infarction was observed. CONCLUSIONS: We
      demonstrated the feasibility and efficiency of skeletal myoblast transplantation
      via the intracoronary route as a promising strategy for improving cardiac
      function in global heart failure.

PMID- 11568059
TI  - Enhanced myocardial angiogenesis by gene transfer with transplanted cells.
AB  - BACKGROUND The combination of myocardial cell transplantation and angiogenic gene
      transfer may improve postinfarction left ventricular (LV) perfusion. We evaluated
      the angiogenic effect of heart cells transfected with vascular endothelial growth
      factor (VEGF) and transplanted into a myocardial scar. METHODS AND RESULTS: Donor
      rat heart cells were transfected with plasmids encoding VEGF(165) and green
      fluorescence protein. Syngeneic adult rats underwent LV cryoinjury to create a
      transmural scar. Three weeks later, 4x10(6) transfected heart cells (n=14),
      untransfected heart cells (n=13), or culture medium (n=16) were transplanted into
      the center of the scar. After 5 weeks, LV function, quantitative histology, and
      regional blood flow were evaluated. Plates of heart cells transfected with
      VEGF(165) produced 6.1 times more intracellular VEGF than nontransfected cells.
      Capillary density (mean+/-SEM) per high-power field in the center of the
      myocardial scar was 1.1+/-0.02 in control rats, 3.9+/-0.11 in untransfected rats,
      and 6.3+/-0.11 in transfected rats (P=0.0002). Capillary density in the border
      zone around the scar was 1.9+/-0.03 in control rats, 6.4+/-0.10 in untransfected
      rats, and 8.7+/-0.16 in transfected rats (P=0.004). Regional blood flow within
      the scar was 8.8+/-0.8% of normalized flow in control hearts, 10.4+/-0.7% in
      hearts transplanted with untransfected cells, but 17.6+/-1.2% in hearts
      transplanted with transfected cells (P=0.03 versus control, P=0.07 versus
      nontransfected). There was no difference in LV function attributable to
      transplantation with transfected cells at the time point studied. CONCLUSIONS:
      Transplantation of heart cells transfected with VEGF induced greater angiogenesis
      than transplantation of unmodified cells. Combined gene transfer and cell
      transplantation strategies may improve postinfarction LV perfusion and function.

PMID- 11568060
TI  - Is skeletal myoblast transplantation clinically relevant in the era of
      angiotensin-converting enzyme inhibitors?
AB  - BACKGROUND: There is compelling experimental evidence that autologous skeletal
      muscle (SM) cell transplantation improves postinfarction cardiac function. This
      study assessed whether this benefit is still manifested in the clinically
      relevant setting of a treatment by ACE inhibitors. METHODS AND RESULTS: A
      myocardial infarction was created in 99 rats by coronary artery ligation. They
      were divided into 4 groups. Two groups did not receive any drug and were
      intramyocardially injected 7 days after the infarct with either culture medium
      alone (control rats, n=16) or autologous SM cells (2.3x10(6) myoblasts)
      previously expanded ex vivo for 7 days (myoblasts, n=24). Two other groups
      received the ACE inhibitor perindoprilat (1 mg. kg(-1). d(-1)), started the day
      of the infarct and continued uninterruptedly thereafter, and underwent time
      matched procedures, that is, they were intramyocardially injected at 7 days after
      infarction with either culture medium alone (ACE inhibitors, n=22) or autologous
      SM cells (2.5x10(6) myoblasts) previously expanded ex vivo for 7 days (ACE
      inhibitors+myoblasts, n=37). Left ventricular function was assessed by 2D
      echocardiography. At the end of the 2-month study, left ventricular ejection
      fraction (%, mean+/-SEM) was increased in all groups (myoblasts, 37.4+/-1.2; ACE
      inhibitors, 31.6+/-1.7; ACE inhibitors+myoblasts, 43.9+/-1.4) compared with that
      in control rats (19.8+/-0.7) (P<0.0001). The improvement in ejection fraction was
      similar in the ACE inhibitor and the myoblast groups (31.6+/-1.7 versus 37.4+/
      1.2, P=0.0636). However, in the ACE inhibitor+myoblast group, this improvement
      was greater than that seen in hearts receiving either treatment alone (43.9+/-1.4
      versus 31.6+/-1.7 in the ACE inhibitor group and 43.9+/-1.4. versus 37.4+/-1.2 in
      the myoblast group, P<0.0001 and P=0.0084, respectively). CONCLUSIONS: These data
      provide further support for the clinical relevance of autologous SM cell
      transplantation in that its cardioprotective effects are additive to those
      observed with ACE inhibitors.

PMID- 11568061
TI  - Normalized diastolic properties after left ventricular assist result from reverse
      remodeling of chamber geometry.
AB  - BACKGROUND: Normalization of diastolic properties after left ventricular (LV)
      assist may result from a change in myocardial material properties, chamber size,
      or both. This study tested the hypothesis that reported normalization of LV
      diastolic properties is primarily due to remodeling of chamber geometry. METHODS
      AND RESULTS: Hearts were obtained at transplantation from 8 patients with dilated
      cardiomyopathy (DCM), 6 patients with DCM plus 33+/-5 days of LV assist, and 3
      patients with no evidence of heart failure. LV assist normalized passive pressure
      volume curves. Chamber dimensions decreased without a change in the ratio of
      radius to wall thickness. Midwall stress-stretch relations predicted from
      pressure-volume and dimension data were not different for DCM and LV assist
      hearts. Passive stress-stretch relations were measured in endocardial trabeculae
      and were not different for DCM and LV assist hearts. Myocyte size and collagen
      area fraction were unchanged at this brief duration of support. CONCLUSIONS:
      These findings are all consistent with the hypothesis that early normalization of
      diastolic properties after LV assist device support results from remodeling of
      chamber geometry, not from changes in tissue stiffness. These data emphasize the
      importance of geometry to ventricular mechanics and demonstrate that reduction of
      heart size does not necessarily produce a reduction in wall stress.

PMID- 11568062
TI  - Quantitative myocardial cytokine expression and activation of the apoptotic
      pathway in patients who require left ventricular assist devices.
AB  - BACKGROUND: Molecular mechanisms underlying the deterioration of patients
      undergoing LV assist device (LVAD) implantation remain poorly understood. We
      studied the cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)
      1beta and IL-6 and the terminal stage of the apoptotic pathway in patients with
      decompensating heart failure who required LVAD support and compared them with
      patients with less severe heart failure undergoing elective heart
      transplantation. METHODS AND RESULTS: Myocardial and serum samples from 23
      patients undergoing LVAD implantation were compared with those from 36 patients
      undergoing elective heart transplantation. Myocardial TNF-alpha mRNA (1.71-fold;
      P<0.05) and protein (3.43+/-0.19 versus 2.95+/-0.10 pg/mg protein; P<0.05) were
      elevated in the LVAD patients. Immunocytochemistry demonstrated TNF expression in
      the myocytes. Serum TNF-alpha was also elevated (12.5+/-1.9 versus 4.0+/-0.4
      pg/mL; P<0.0001) in the LVAD patients. IL-6 mRNA (2.57-fold higher; P<0.005) and
      protein (27.83+/-9.35 versus 4.26+/-1.24 pg/mg protein; P<0.001) were higher in
      the LVAD candidates, as was serum IL-6 (79.3+/-23.6 versus 7.1+/-1.6 pg/mL;
      P<0.0001). Interleukin-1beta mRNA expression was 9.78-fold higher in the LVAD
      patients (P<0.001). iNOS mRNA expression was similar to that in advanced heart
      failure patients and was not further elevated in the LVAD patients. Levels of
      procaspase-9 (8.02+/-0.91 versus 6.16+/-0.43 oligodeoxynucleotide [OD] units;
      P<0.01), cleaved caspase-9 (10.02+/-1.0 versus 7.34+/-0.40 OD units; P<0.05),
      intact and spliced DFF-45 (4.58+/-0.75 versus 2.84+/-0.23 OD units; P<0.05) were
      raised in LVAD patients, but caspase-3 and human nuclease CPAN were not.
      CONCLUSIONS: Elevated TNF-alpha, IL-1beta, and IL-6 and alterations in the
      apoptotic pathway were found in the myocardium and elevated TNF-alpha and IL-6 in
      serum of deteriorating patients who required LVAD support. These occurrences may
      have therapeutic implications and influence the timing of LVAD insertion.

PMID- 11568063
TI  - Initial effects of the left ventricular repair by plication may not last long in
      a rat ischemic cardiomyopathy model.
AB  - BACKGROUND: Long term effects of left ventricle (LV) repair surgery (LVR) for
      ischemic cardiomyopathy are not well understood. METHODS AND RESULTS: Sixty-nine
      rats developed ischemic cardiomyopathy with large akinetic LV area 4 weeks after
      the left anterior descending artery was ligated. In a second surgery 4 weeks
      later, 33 rats underwent LVR by plication of the akinetic LV area (LVR group),
      and 36 underwent rethoracotomy alone (sham group). No medication was used in
      either group. All rats survived the second surgery. LV end-diastolic dimension as
      measured by echocardiography, LV fractional shortening, and the maximal end
      systolic pressure-volume relationship (E(max)) as calculated from the data by
      catheter-tipped manometer and echocardiography improved in the LVR group after
      the second surgery, but LV end-diastolic dimension and E(max) gradually
      deteriorated as time passed. LV end-diastolic pressure improved 1 week after LVR
      but rose significantly 4 weeks after LVR. Brain natriuretic peptide mRNA was
      lower in the LVR group than in the sham group 1 week after LVR but not 4 weeks
      postoperatively. CONCLUSIONS: Initial improvement in LV function and
      neurohormonal status after LVR did not last for 4 weeks in this rat model when
      untreated medically. The mechanism of deterioration should be elucidated to
      improve long-term results of LVR.

PMID- 11568064
TI  - Protection from reperfusion injury after cardiac transplantation by inhibition of
      adenosine metabolism and nucleotide precursor supply.
AB  - BACKGROUND: Adenosine (Ado) triggers numerous protective mechanisms in the heart
      that may attenuate ischemia-reperfusion injury in cardiac grafts. We aimed to
      establish whether sustained increase in endogenous Ado production by the combined
      application of Ado metabolism inhibitors and nucleotide precursors attenuates
      reperfusion injury in transplanted hearts. METHODS AND RESULTS: Rat hearts were
      collected after the infusion of St Thomas' Hospital cardioplegic solution, stored
      at 4 degrees C for 4 hours, and heterotopically transplanted into the abdomen of
      recipient rats. A solution containing Ado deaminase inhibitor erythro-9(2-hydroxy
      3-nonyl)adenine, Ado kinase inhibitor 5'-aminoadenosine, and nucleotide
      precursors adenine and ribose was administered at the time of reperfusion in the
      treated group, whereas saline was administered to control animals. After 1 or 24
      hours, mechanical function of the transplanted hearts was evaluated in an ex vivo
      perfusion system followed by the determination of myocardial ATP with related
      metabolites and measurement of the activity of neutrophil-specific enzyme
      myeloperoxidase in cardiac homogenates. After 24 hours of reperfusion, maximum
      left ventricular developed pressure increased from 87.0+/-6.8 mm Hg (mean+/-SEM)
      in controls to 118.1+/-8.2 mm Hg in the treated group (P<0.05), ATP increased
      from 11.0+/-0.8 micromol/g dry wt in controls to 15.1+/-1.2 micromol/g dry wt in
      the treated group (P<0.01), and myeloperoxidase activity decreased from 2.23+/
      0.60 U/g wet wt in controls to 0.58+/-0.12 U/g wet wt in the treated group
      (P<0.001). No differences in cardiac function, ATP, or myeloperoxidase activity
      were observed between the treated group and controls after 1 hour of reperfusion.
      CONCLUSIONS: The administration of Ado metabolism inhibitors with nucleotide
      precursors causes a sustained increase in endogenous Ado production and exerts a
      potent protective effect against reperfusion injury in transplanted hearts.
      Improved cardiac function and elevated ATP concentration were accompanied by
      complete amelioration of neutrophil infiltration in treated hearts, suggesting
      that reduction in postischemic inflammation could be an important mechanism of
      this protective effect.

PMID- 11568065
TI  - Modified ultrafiltration reduces morbidity after adult cardiac operations: a
      prospective, randomized clinical trial.
AB  - BACKGROUND: Extracorporeal circulation contributes to morbidity after open-heart
      surgery by causing a systemic inflammatory reaction. Modified ultrafiltration is
      a technique able to remove the fluid overload and inflammatory mediators
      associated with use of cardiopulmonary bypass. It has been shown to reduce
      morbidity after cardiac operations in children, but the impact on adult cardiac
      procedures is unknown. METHODS AND RESULTS: Five hundred seventy-three
      consecutive adult patients were prospectively randomized to either
      ultrafiltration after cardiopulmonary bypass (treatment) or to no ultrafiltration
      (control). Parsonnet score was used to assess the severity of the patients'
      clinical conditions. Analysis was done with Student's t test or Mann-Whitney U
      test for continuous variables and Fisher's exact test or Pearson's chi(2) for
      discrete variables. Hospital mortality was 2.5% (7 of 284) in the treatment group
      versus 3.8% (11 of 289) in the control group (P=0.357). Hospital morbidity was
      lower in treated patients (66 of 284 [23.2%] versus 117 of 289 [40.5%],
      P=0.0001). Cardiac morbidity was similar (26 of 284 [9.1%] versus 35 of 289
      [12.1%], P=0.251), whereas significantly lower rates of respiratory (20 of 284
      [7.0%] versus 36 of 289 [12.5%], P=0.029), neurological (5 of 284 [1.8%] versus
      14 of 289 [4.8%], P=0.039), and gastrointestinal (0 of 284 versus 4 of 289
      [1.4%], P=0.044) complications were found in treated patients. Transfusion
      requirements were also lower in treated patients (1.66+/-2.6 versus 2.25+/-3.8
      U/patient, P=0.039). Duration of intensive care (39.9+/-49.2 versus 46.3+/-72.8
      hours, P=0.218) and hospital stay (7.6+/-3.5 versus 7.9+/-4.4 days, P=0.372) were
      comparable. CONCLUSIONS: Modified ultrafiltration after cardiopulmonary bypass is
      associated with a lower prevalence of early morbidity and lower blood transfusion
      requirements. The impact on length of hospital stay needs further analysis.
      Routine application of modified ultrafiltration after adult cardiac operations is
      warranted.

PMID- 11568066
TI  - Effects of hematocrit on cerebral microcirculation and tissue oxygenation during
      deep hypothermic bypass.
AB  - BACKGROUND: One rationale for hemodilution during hypothermic cardiopulmonary
      bypass (CPB) has been improved microcirculation. However, the optimal degree of
      hemodilution remains unclear. We therefore studied cerebral microcirculation and
      tissue oxygenation in a new intravital microscopic model at 3 different
      hematocrit (Hct) values. METHODS AND RESULTS: Three groups of 5 piglets with a
      cranial window over the parietal cortex underwent cooling at Hct of 10%, 20%, or
      30%, followed by 1-hour deep hypothermic circulatory arrest (DHCA) and rewarming
      on CPB. For assessment of functional capillary density (FCD), plasma was labeled
      with fluorescein-isothiocyanate-dextran. Rhodamine-stained leukocytes were
      observed in postcapillary venules with analysis for adhesion and rolling. NADH, a
      natural intracellular fluorophore that increases during ischemia, was measured
      densitometrically during bypass and DHCA. FCD did not significantly differ from
      baseline during cooling in any group. However, during early reperfusion (5
      minutes) after DHCA, the FCD was significantly higher in the Hct 30% group than
      in the Hct 10% group. Leukocyte adherence decreased in all groups during CPB and
      was only moderately increased at the end of the experiment. However, severe
      hemodilution (Hct 10%) was associated with a significantly greater number of
      rolling leukocytes relative to Hct 30%. CONCLUSIONS: Higher Hct does not impair
      cerebral microcirculation and reduces white cell/endothelial activation after
      deep hypothermic bypass and circulatory arrest. Severe hemodilution (Hct 10%)
      results in evidence of inadequate cerebral tissue oxygenation during the cooling
      phase of CPB. This study suggests that Hct of 30% is preferable relative to lower
      Hct values during hypothermic CPB, particularly if DHCA is used.

PMID- 11568067
TI  - Aprotinin but not epsilon-aminocaproic acid decreases interleukin-10 after
      cardiac surgery with extracorporeal circulation: randomized, double-blind,
      placebo-controlled study in patients receiving aprotinin and epsilon-aminocaproic
      acid.
AB  - BACKGROUND: Extracorporeal circulation induces a systemic inflammatory response,
      which may adversely affect organ function. One manifestation of this response is
      increased fibrinolysis. Antifibrinolytic drugs such as aprotinin and epsilon
      aminocaproic acid have been effective in reducing fibrinolysis and blood loss
      after extracorporeal circulation; however, the effects of antifibrinolytic drugs
      on proinflammatory and anti-inflammatory mediators are not known. This study
      examined the effects of aprotinin and epsilon-aminocaproic acid on plasma levels
      of proinflammatory [interleukin-6 (IL-6)] and anti-inflammatory [interleukin-10
      (IL-10)] cytokines during and after extracorporeal circulation. METHODS AND
      RESULTS: Seventy-two patients undergoing coronary artery bypass grafting with
      extracorporeal circulation were randomly assigned in a double-blind study to
      receive high-dose aprotinin, epsilon-aminocaproic acid, or saline placebo. Plasma
      levels of IL-6 and IL-10 were measured at 5 time points before, during, and after
      extracorporeal circulation. In all 3 groups, both IL-6 and IL-10 rose
      significantly after institution of extracorporeal circulation and remained
      elevated through the first postoperative day. Compared with saline, aprotinin
      significantly reduced IL-10 (P=0.02) and peak IL-6 (P=0.02) after extracorporeal
      circulation. In contrast, none of the reductions in IL-6 and IL-10 by epsilon
      aminocaproic acid achieved statistical significance. Both aprotinin and epsilon
      aminocaproic acid decreased blood loss compared with saline, but there was no
      significant difference in the number of patients receiving blood products among
      the treatment groups. CONCLUSIONS: These data suggest that aprotinin and epsilon
      aminocaproic acid differ in their effects on the inflammatory response to
      extracorporeal circulation. Aprotinin but not epsilon-aminocaproic acid appears
      to attenuate the rise in the proinflammatory and anti-inflammatory cytokines IL-6
      and IL-10. Further studies will be required to determine if these cytokine
      alterations translate to changes in clinical outcomes.

PMID- 11568068
TI  - Passive containment and reverse remodeling by a novel textile cardiac support
      device.
AB  - BACKGROUND: Progressive remodeling and dilation of cardiac chambers is
      responsible in part for myocardial dysfunction in chronic heart failure.
      Preclinical studies with suitable animal models indicate that a passive cardiac
      constraint device can promote reverse remodeling, with improvement in cardiac
      function. We hypothesize that such a device could provide benefit for stable
      heart failure patients in New York Heart Association (NYHA) class II and III.
      METHODS AND RESULTS: From April 1999 to March 2000, 27 patients received Acorn's
      Cardiac Support Device (CSD) during an initial safety/feasibility study. In 11
      patients, the only surgical measure was CSD placement. Most patients suffered
      from idiopathic cardiomyopathy; 4 were in NYHA class II, one was in class II/III,
      and 6 were in class III. All were stable on intensive medical treatment. The CSD,
      a textile polyester device, was fitted snugly around the heart during surgery.
      All patients survived surgery and recovered smoothly. Three months after surgery,
      56% of patients were in NYHA class I, 33% were in class II, and 11% were in class
      II/III. Echocardiography showed an improvement in left ventricular ejection
      fraction from an average of 22% to 28% and 33% at 3 and 6 months, respectively.
      Simultaneously, the left ventricular end-diastolic dimension decreased from 74 mm
      to 68 mm and 65 mm, respectively. Mitral valve regurgitation (on a scale of 0 to
      4+) decreased from 1.3 to 0.7 by 3 months. Quality-of-life indices correlated
      with the apparent reversal of ventricular remodeling. Preoperative cardiac
      medications remained virtually unchanged after implant. CONCLUSIONS: In the short
      and intermediate-term, CSD implantation seems to ameliorate symptoms and improve
      cardiac and functional performance in heart failure patients. Worldwide
      randomized trials are currently underway.

PMID- 11568069
TI  - Aprotinin, blood loss, and renal dysfunction in deep hypothermic circulatory
      arrest.
AB  - BACKGROUND: The technique of deep hypothermic circulatory arrest (DHCA) for
      cardiothoracic surgery is associated with increased risk for perioperative blood
      loss and renal dysfunction. Although aprotinin, a serine protease inhibitor,
      reduces blood loss in patients undergoing cardiopulmonary bypass, its use has
      been limited in the setting of DHCA because of concerns regarding aprotinin
      induced renal dysfunction. Therefore, we assessed the affect of aprotinin on both
      blood transfusion requirements and renal function in patients undergoing
      cardiovascular surgery and DHCA. METHODS AND RESULTS: We reviewed the records of
      853 patients who underwent aortic or thoracoabdominal surgery at Stanford
      University Medical Center between January 1992 and March 2000. Two hundred three
      of these patients were treated with DHCA, and 90% (183) survived for more than 24
      hours. Preoperative patient characteristics and intraoperative and postoperative
      clinical and surgical variables were recorded, and creatinine clearance (CRCl)
      was calculated for the preoperative and postoperative periods; renal dysfunction
      was prospectively defined as a 25% reduction in CRCl. The association between
      perioperative variables, including aprotinin use, and renal dysfunction was
      assessed by ANOVA techniques. Total urine output was 1294+/-1024 mL and 3492+/
      1613 mL during and after surgery, respectively. CRCl decreased significantly
      after DHCA from 86+/-8 mL/min (before surgery) to 67+/-4 mL/min (in the intensive
      care unit) (P<0.01). Thirty-eight percent of patients (70 of 183) had
      postoperative renal dysfunction. Multivariate regression analyses identified 5
      factors independently associated with a >25% reduction in CRCl: requirement for
      >/=5 U of packed red blood cells(P=0.0002; OR=2.1), </=800 mL of urine collected
      in the operating room (P=0.0011; OR=1.9), nonuse of dopamine (P=0.0430; OR=1.6),
      hematocrit </=21 mg% (P=0.0343; OR=1.5), and </=2100 mL of urine during the first
      24 hours in the intensive care unit (P=0.0039; OR=2.0). Aprotinin did not
      increase the likelihood of postoperative renal dysfunction (P=0.951), nor did it
      significantly reduce packed red blood cell transfusion requirements in either
      primary (n=107) (P=0.456) or reoperative cardiovascular (n=76) (P=0.176)
      procedures. During the operative period, the aprotinin group received a greater
      number of units of platelets (10.0 versus 6.6 U, P<0.012), fresh frozen plasma
      (4.8 versus 3.1 U, P<0.03), and cryoprecipitate (9.9 versus 5.4 U, P<0.002) than
      patients not prescribed aprotinin. Similarly, patients given aprotinin received
      more cryoprecipitate in the intensive care unit (7.3 versus 3.0 U, P<0.024).
      CONCLUSIONS: These data suggest that the administration of aprotinin to patients
      treated with DHCA does not increase the risk of renal dysfunction. However,
      aprotinin may not ameliorate the problem of perioperative blood loss in DHCA.
      Patients with greater requirements for packed red blood cell transfusions or
      reduced urine production are more likely to have postoperative renal dysfunction.
      Dopamine may provide renal protection in the setting of DHCA.

PMID- 11568070
TI  - Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis in
      cystic medial degeneration associated with Marfan's syndrome.
AB  - BACKGROUND: Cystic medial degeneration (CMD) is a histological abnormality that
      is common in the aortic diseases associated with Marfan's syndrome (MFS).
      Although little known about the mechanism underlying CMD, several recent reports
      have demonstrated that vascular smooth muscle cell (VSMC) apoptosis could play a
      substantial role in CMD. On the other hand, angiotensin II (Ang II) has been
      reported to play an important role in the regulation of VSMC growth and apoptosis
      via the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R). METHODS AND
      RESULTS: To elucidate the role of Ang II signaling via the Ang II receptors in
      CMD, we investigated AT1R and AT2R mRNA expression and tissue concentration of
      Ang II in MFS aortas (n=10) and control aortas (n=12). Furthermore, we examined
      the effects of an ACE inhibitor, an AT1R blocker, and an AT2R blocker on serum
      deprivation-induced VSMC apoptosis by organ culture system. AT1R expression was
      significantly decreased (P<0.01) and AT2R expression was significantly increased
      (P<0.001) in MFS aortas compared with control aortas, and tissue Ang II
      concentration was significantly higher in CMD than in the control condition
      (P<0.01). Both the ACE inhibitor and AT2R blocker significantly inhibited serum
      deprivation-induced VSMC apoptosis (P<0.05), although the AT1R blocker did not
      inhibit apoptosis in cultured aortic media from MFS patients. CONCLUSIONS:
      Accelerated ACE-dependent Ang II formation and signaling via upregulated AT2R
      play a pivotal role in VSMC apoptosis in CMD, and the ACE inhibitor could have
      clinical value in the prevention and treatment of CMD.

PMID- 11568071
TI  - Plasma levels of metalloproteinases-3 and -9 as markers of successful abdominal
      aortic aneurysm exclusion after endovascular graft treatment.
AB  - BACKGROUND: Structural alterations of aortic wall resulting from degradation of
      matrix proteins by matrix metalloproteinases (MMPs) characterize abdominal aortic
      aneurysms (AAAs). No studies have compared circulating levels of MMPs after
      endovascular graft (EVG) exclusion in comparison with open surgical repair (OSR)
      in patients affected by AAA. METHODS AND RESULTS: An abdominal angiography and CT
      scan were performed in all patients at the time of enrollment. A spiral CT scan
      was performed at 6 months to detect presence of endoleaks. MMP-3 and MMP-9 levels
      were measured before EVG (n=30) and OSR (n=15) treatments and at 1, 3, and 6
      months of follow-up by a sandwich ELISA technique. Healthy volunteers (n=10) were
      used as control subjects. Immunohistochemical staining for MMP-9 and MMP-3 was
      performed on tissue samples from surgical cases. Both MMP-9 and MMP-3 mean basal
      levels were significantly higher in patients affected by AAA than in control
      subjects (32.3+/-20.7 ng/mL for EVG and 28+/-9.9 ng/mL for OSR versus 8.9+/-2.5
      ng/mL, 2P<0.05; 18.3+/-9.7 ng/mL and 26.7+/-10.8 ng/mL versus 8.2+/-5.3 ng/mL,
      2P<0.001). In the OSR group, both MMP-9 and MMP-3 mean levels decreased after
      surgery (28+/-9.9 ng/mL at basal versus 14.7+/-6.6 ng/mL at 6 months, 2P<0.001;
      26.7+/-10.8 versus 12+/-5.3 ng/mL; 2P<0.001). In the EVG group, a statistically
      significant difference at 6-month follow-up in MMP-9 and MMP-3 mean plasma values
      was detected in patients who had endoleakage in comparison with patients without
      endoleakage (44.3+/-20.7 versus 14.6+/-7.0 ng/mL, 2P<0.005; 25+/-11.5 versus
      10.3+/-5.4 ng/mL, 2P<0.005). CONCLUSIONS: After EVG exclusion, MMP-9 and MMP-3
      levels decreased to a level similar to that of patients undergoing OSR. In
      addition, a lack of decrease in MMP levels after EVG exclusion may help in
      identifying patients who will have endoleakage and consequent aneurysm expansion
      caused by continuous sac pressurization during follow-up.

PMID- 11568072
TI  - All-blood (miniplegia) versus dilute cardioplegia in experimental surgical
      revascularization of evolving infarction.
AB  - BACKGROUND: The advantages of blood cardioplegia include the oxygen-carrying
      capacity, superior oncotic and buffering properties, and endogenous antioxidants
      contained in blood. However, the partial dilution of blood in 4:1
      (blood:crystalloid) cardioplegic solutions may nullify these advantages and
      progressively dilute blood during continuous retrograde delivery. This study
      tested the hypothesis that all-blood (66:1) cardioplegia provides superior
      myocardial protection compared with dilute (4:1) cardioplegia delivered in a
      continuous retrograde modality during surgical reperfusion of evolving myocardial
      infarction. METHODS AND RESULTS: After 60 minutes of left anterior descending
      coronary artery (LAD) occlusion, anesthetized canines were placed on
      cardiopulmonary bypass and randomized to either all-blood cardioplegia (AB group)
      or dilute blood cardioplegia (Dil group). After cross clamping, arrest was
      induced with 5 minutes of tepid (30 degrees C) antegrade potassium all-blood or
      dilute blood cardioplegia and maintained with tepid retrograde coronary sinus
      cardioplegia for a total of 1 hour. The LAD was released after 30 minutes of
      arrest, simulating revascularization. The cardioplegia hematocrit for the Dil
      group was lower than that for the AB group (7+/-1% versus 12+/-2%, P<0.05); at
      the end of bypass, systemic hematocrit was lower in the Dil group than in the Ab
      group (15+/-1% versus 20+/-1%, P<0.05). Infarct size (triphenyltetrazolium
      chloride staining) was comparable between the AB and Dil groups (29.6+/-2.9%
      versus 30.3+/-3.9% of area at risk), and there was no difference in area-at-risk
      myocardium systolic shortening (by sonomicrometry, -0.3+/-1% versus -0.4+/-1%).
      Tissue edema after bypass tended to be greater in the Dil group compared with the
      AB group in the heart (82+/-0% versus 81+/-1%), lung (79+/-1% versus 78+/-1%),
      liver (75+/-1% versus 74+/-0%), and skeletal muscle (76+/-1% versus 73+/-2%) and
      was significantly greater in the duodenum (80+/-1% versus 79+/-1%, P<0.05) and
      kidney (82+/-1% versus 79+/-1%, P<0.05). Postexperimental endothelial function
      (relaxation of acetylcholine) was impaired in LADs of the AB group versus the Dil
      group (59+/-6% versus 77+/-5%, P<0.05). CONCLUSIONS: Both all-blood cardioplegia
      and dilute cardioplegia have disadvantages, but these do not have an impact on
      the pathogenesis of infarct size or recovery of regional contractile function.

PMID- 11568073
TI  - Heat shock protein 70 gene transfection protects mitochondrial and ventricular
      function against ischemia-reperfusion injury.
AB  - BACKGROUND: Upregulation of heat shock protein 70 (HSP70) is beneficial in
      cardioprotection against ischemia-reperfusion injury, but the mechanism of action
      is unclear. We studied the role of HSP70 overexpression through gene therapy on
      mitochondrial function and ventricular recovery in a protocol that mimics
      clinical donor heart preservation. METHODS AND RESULTS: Hemagglutinating virus of
      Japan (HVJ)-liposome technique was used to transfect isolated rat hearts via
      intracoronary infusion of either the HSP70 gene (HSP group, n=16) or no gene (CON
      group, n=16), which was heterotopically transplanted into recipient rats. Four
      days after surgery, hearts were either perfused on a Langendorff apparatus for 30
      minutes at 37 degrees C (preischemia studies [n=8/group]) or perfused for 30
      minutes at 37 degrees C, cardioplegically arrested for 4 hours at 4 degrees C,
      and reperfused for 30 minutes at 37 degrees C (postischemia studies [n=8/group]).
      Western blotting and immunohistochemistry confirmed HSP70 upregulation in the HSP
      group. Postischemic mitochondrial respiratory control indices (RCIs) were
      significantly better preserved in HSP than in CON hearts: NAD(+)-linked RCI
      values were 9.54+/-1.1 versus 10.62+/-0.46 before ischemia (NS) but 7.98+/-0.69
      versus 1.28+/-0.15 after ischemia (P<0.05), and FAD-linked RCI values were 6.87+/
      0.88 versus 6.73+/-0.93 before ischemia (NS) but 4.26+/-0.41 versus 1.34+/-0.13
      after ischemia (P<0.05). Postischemic recovery of mechanical function was greater
      in HSP than in CON hearts: left ventricular developed pressure recovery was
      72.4+/-6.4% versus 59.7+/-5.3% (P<0.05), maximum dP/dt recovery was 77.9+/-6.6%
      versus 52.3+/-5.2% (P<0.05), and minimum dP/dt recovery was 72.4+/-7.2% versus
      54.8+/-6.9% (P<0.05). Creatine kinase release in coronary effluent after
      reperfusion was 0.20+/-0.04 versus 0.34+/-0.06 IU. min(-1). g wet wt(-1) (P<0.05)
      in HSP versus in CON hearts. CONCLUSIONS: HSP70 upregulation protects
      mitochondrial function after ischemia-reperfusion injury; this was associated
      with improved preservation of ventricular function. Protection of mitochondrial
      function may be important in the development of future cardioprotective
      strategies.

PMID- 11568074
TI  - Overexpression of interleukin-1 receptor antagonist provides cardioprotection
      against ischemia-reperfusion injury associated with reduction in apoptosis.
AB  - BACKGROUND: Interleukin-1 (IL-1) plays a role in mediating acute inflammation
      during ischemia-reperfusion (I/R) injury in the heart, which leads to both
      necrosis and apoptosis of cardiomyocytes. IL-1 receptor antagonist (IL-1ra) is
      known to inhibit the effects of IL-1alpha and IL-1beta, resulting in attenuated
      inflammatory injury, and to protect cells from IL-1beta-induced apoptosis in
      vitro. We hypothesized that IL-1ra overexpression would provide cardioprotection
      by reducing inflammation-mediated myocardial damage including apoptosis after I/R
      injury in vivo. METHODS AND RESULTS: Rat hearts were transfected with human
      secreted-type IL-1ra gene by intracoronary infusion of Hemagglutinating Virus of
      Japan liposome and were heterotopically transplanted. IL-1ra overexpression in
      these hearts was confirmed by enzyme immunoassay and immunohistochemistry.
      Myocardial tolerance of the transplanted heart was evaluated with the use of a
      novel system in which the heart, existing within the recipient's abdomen, was
      given 30 minutes of ischemia by left coronary artery occlusion and 24 hours of
      reperfusion. Consequently, infarct size was decreased in IL-1ra-transfected
      hearts compared with control-transfected ones (26.9+/-3.2% versus 46.2+/-3.0%,
      P=0.001), corresponding to lower myocardial myeloperoxidase activity (2.20+/-0.69
      versus 6.82+/-1.19 U/g wet wt, P<0.001) and decreased neutrophil infiltration in
      histological study. Terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling and DNA-laddering studies demonstrated that cardiomyocyte apoptosis was
      attenuated in IL-1ra-transfected hearts (21.4+/-3.3 versus 41.4+/-3.4%, P=0.002),
      correlating with reduced post I/R upregulation of Bax, Bak, and caspase-3.
      CONCLUSIONS: IL-1ra introduced by gene transfection protected myocardium from I/R
      injury by attenuating the inflammatory response, which was associated with
      decreased apoptosis. This suggests a potentially important role of IL-1/IL-1ra in
      myocardial I/R injury and the value of IL-1ra-gene therapy for myocardial
      preservation.

PMID- 11568075
TI  - Time course of functional recovery of stunned and hibernating segments after
      surgical revascularization.
AB  - BACKGROUND: Recovery of function is possible in patients with ischemic
      cardiomyopathy when left ventricular dysfunction is caused by stunning or
      hibernation. It is plausible that recovery of function after revascularization
      may take a longer time in hibernating myocardium compared with stunned
      myocardium. Accordingly, the time courses of functional recovery in hibernating
      and stunned myocardium were compared. METHODS AND RESULTS: Patients (n=26) with
      ischemic cardiomyopathy undergoing surgical revascularization were studied;
      regional perfusion (resting (201)Tl single-photon emission CT), glucose
      utilization ((18)F-2-deoxyglucose single-photon emission CT), and contractile
      function (2D echocardiography) were assessed before revascularization.
      Dysfunctional segments with normal perfusion/glucose utilization were considered
      to be stunned, and dysfunctional segments with reduced perfusion/preserved
      glucose utilization were considered to be hibernating. Contractile function was
      reevaluated 3 months (early) and 14 months (late) after revascularization. Of the
      266 dysfunctional segments, 57 (22%) were stunned, 62 (23%) were hibernating, and
      147 (55%) were scar tissue. In stunned myocardium, contractile function improved
      significantly at 3 months, without further improvement at 14 months; 61% of the
      stunned segments improved at 3 months, and 9% improved at 14 months. In
      hibernating myocardium, contractile function improved at 3 months, with a further
      improvement at 14 months; 31% of the hibernating segments improved at 3 months,
      and 61% showed (additional) recovery at 14 months. CONCLUSIONS: Stunned
      myocardium is likely to demonstrate early recovery of function, whereas
      hibernating myocardium may take a longer time to (fully) recover in function
      after revascularization.

PMID- 11568076
TI  - Biochemical and structural evidence for pig myocardium adherens junction
      disruption by cardiopulmonary bypass.
AB  - BACKGROUND: Given that cardiopulmonary bypass (CPB) is associated with edema and
      heart dysfunction and that adherens junctions may regulate vascular permeability
      barrier integrity and cardiomyocyte function, we investigated adherens junction
      protein steady-state levels in a pig model of CPB. METHODS AND RESULTS: Pigs were
      subjected to normothermic CPB for 90 minutes, followed by post-CPB perfusion for
      90 minutes. Atrial and ventricular myocardium tissue samples were harvested
      before institution of bypass (basal levels) and at the end of post-CPB perfusion.
      Adherens junctions were analyzed by either total lysate or cadherin
      immunoprecipitates that were immunoblotted for pan-cadherin, VE-cadherin, beta
      catenin, and gamma-catenin. Adherens junction solubility was addressed with
      Triton X-100 extraction. Frozen tissue sections were labeled with the same
      antibodies, and adherens junctions were visualized by confocal microscopy.
      Immunoblotting of total lysates revealed an increase in smaller-molecular-weight
      fragments of VE-cadherin, beta-catenin, and gamma -catenin after post-CPB
      perfusion, indicating partial protein degradation. Smaller-molecular-weight
      fragments recognized by VE-cadherin and beta-catenin antibodies were also
      obtained from VE-cadherin immunoprecipitation, indicating degradation of
      endothelial cell adherens junctions. A prominent increase in adherens junction
      complex solubility was observed in post-CPB perfusion samples. Confocal
      microscopy of hearts obtained before CPB showed a continuous, homogeneous pattern
      of cell-cell labeling that contrasted with an irregular, discontinuous,
      punctuate, or zigzag pattern observed in post-CPB perfusion samples,
      corroborating biochemical data. CONCLUSIONS: These results indicate that CPB is
      associated with signs of degradation of endothelial and cardiomyocytes adherens
      junctions, pointing to a molecular mechanism leading to increased vascular
      permeability and cardiomyocyte dysfunction.

PMID- 11568077
TI  - Gelatin sheet incorporating basic fibroblast growth factor enhances healing of
      devascularized sternum in diabetic rats.
AB  - BACKGROUND: Poor healing of the sternum often limits the use of bilateral
      internal thoracic arteries (BITAs) after coronary bypass surgery in diabetic
      patients. We have reported that a gelatin sheet that incorporates basic
      fibroblast growth factor (bFGF) accelerates sternal healing after BITA removal in
      normal rats. This study evaluated the effects of the above method for sternal
      healing in diabetic animals. METHODS AND RESULTS: Diabetic Wistar rats with blood
      glucose levels >400 mg/dL and body-weight loss >20 g were established by a single
      intravenous injection of streptozotocin (55 mg/kg). After median sternotomy and
      BITA removal, 16 diabetic rats received either a gelatin sheet that incorporated
      bFGF (100 microg/sheet) on the posterior table of the sternum (FGF group, n=9) or
      no gelatin sheet (control, n=7). Peristernal blood flow, as measured by a
      noncontact laser Doppler 4 weeks after surgery in the FGF group, recovered to the
      preoperative level (106+/-10% versus 82+/-9%, P<0.01), and marked angiogenesis
      was also observed around the sternum in the FGF group (30.5+/-3.2 versus 15.8+/
      2.7 vessels/unit area, P<0.01). Deep sternal wound complications developed in 5
      control rats but only in 1 rat in the FGF group (P<0.05). In the FGF group,
      histological examination showed improved sternal healing (excellent in 6 rats and
      slow/poor healing in 3). Bone mineral content as assessed by dual-energy x-ray
      absorptometry was greater in the FGF group (75.9+/-18.1 versus 48.9+/-10.7 mg,
      P<0.05). Bone mineral density of the sternum was similar between the 2 groups.
      CONCLUSIONS: A gelatin sheet that incorporates bFGF may offset sternal ischemia
      and accelerate sternal bone regeneration and healing, even in diabetic patients.

PMID- 11568078
TI  - Relationship between early diastolic intraventricular pressure gradients, an
      index of elastic recoil, and improvements in systolic and diastolic function.
AB  - BACKGROUND: Early diastolic intraventricular pressure gradients (IVPGs) have been
      proposed to relate to left ventricular (LV) elastic recoil and early ventricular
      "suction." Animal studies have demonstrated relationships between IVPGs and
      systolic and diastolic indices during acute ischemia. However, data on the
      effects of improvements in LV function in humans and the relationship to IVPGs
      are lacking. METHODS AND RESULTS: Eight patients undergoing CABG and/or infarct
      exclusion surgery had a triple-sensor high-fidelity catheter placed across the
      mitral valve intraoperatively for simultaneous recording of left atrial (LA),
      basal LV, and apical LV pressures. Hemodynamic data obtained before bypass were
      compared with those with similar LA pressures and heart rates obtained after
      bypass. From each LV waveform, the time constant of LV relaxation (tau),
      +dP/dt(max), and -dP/dt(max) were determined. Transesophageal echocardiography
      was used to determined end-diastolic (EDV) and end-systolic (ESV) volumes and
      ejection fractions (EF). At similar LA pressures and heart rates, IVPG increased
      after bypass (before bypass 1.64+/-0.79 mm Hg; after bypass 2.67+/-1.25 mm Hg;
      P<0.01). Significant improvements were observed in ESV, as well as in apical and
      basal +dP/dt(max), -dP/dt(max), and tau (each P<0.05). Overall, IVPGs correlated
      inversely with both ESV (IVPG=-0.027[ESV]+3.46, r=-0.64) and EDV (IVPG=
      0.027[EDV]+4.30, r=-0.70). Improvements in IVPGs correlated with improvements in
      apical tau (Deltatau =5.93[DeltaIVPG]+4.76, r=0.91) and basal tau (Deltatau
      =2.41[DeltaIVPG]+5.13, r=-0.67). Relative changes in IVPGs correlated with
      changes in ESV (DeltaESV=-0.97[%DeltaIVPG]+23.34, r=-0.79), EDV (DeltaEDV=
      1.16[%DeltaIVPG]+34.92, r=-0.84), and EF (DeltaEF=0.38[%DeltaIVPG]-8.39, r=0.85).
      CONCLUSIONS: Improvements in LV function also increase IVPGs. These changes in
      IVPGs, suggestive of increases in LV suction and elastic recoil, correlate
      directly with improvements in LV relaxation and ESV.

PMID- 11568079
TI  - Expression of endomyocardial nitric oxide synthase and coronary endothelial
      function in human cardiac allografts.
AB  - BACKGROUND: Inducible nitric oxide synthase (iNOS) is expressed and is
      functionally active in the presence of transplant arteriosclerosis. However, the
      early involvement of iNOS in alterations of microvascular endothelial function in
      the absence of preexisting lesions remains unclear; this information would be of
      prognostic value. We studied the course of iNOS mRNA expression, transcardiac
      nitric oxide production, and their potential association with microvascular
      coronary endothelial dysfunction in human cardiac allografts. METHODS AND
      RESULTS: A total of 42 patients were studied at 1, 6, and 12 months after heart
      transplantation. Microvascular coronary flow velocity reserve (CFVR) was tested
      in an endothelium-dependent (acetylcholine) and -independent manner (adenosine)
      using a Doppler flow wire. Endomyocardial iNOS expression was determined by
      reverse transcription polymerase chain reaction. iNOS protein and nitrotyrosine
      levels were detected by immunohistochemistry. Transcardiac plasma nitrite/nitrate
      (NOx) levels were measured by the Griess reaction. CFVR was impaired in 26.1% of
      patients (n=11) at 1 month and in 31% of patients (n=13) at 12 months after heart
      transplantation. Patients who developed impaired CFVR in the first year showed a
      significant increase in iNOS gene expression. Patients with impairment of CFVR 1
      month after heart transplantation had higher levels of iNOS mRNA than patients
      with a normal CFVR. Patients with an initial impairment of CFVR who did not
      improve over time presented with significantly higher iNOS mRNA levels. iNOS
      protein and nitrotyrosine were expressed in the endomyocardial vessels of
      patients with impaired CFVR. Transcardiac NOx release was higher in patients with
      impaired CFVR. CONCLUSIONS: In human cardiac allografts, microvascular
      endothelial dysfunction is associated with an enhanced endomyocardial iNOS mRNA
      expression and higher transcardiac NOx production and is accompanied by the
      expression of nitrotyrosine protein, suggesting peroxynitrite plays a role in the
      disease process. The data from the present study suggest an important role for
      the iNOS/nitric oxide pathway in the regulation of microvascular function in the
      absence of preexisting atherosclerotic lesions.

PMID- 11568080
TI  - Comparison of nitric oxide release and endothelium-derived hyperpolarizing factor
      mediated hyperpolarization between human radial and internal mammary arteries.
AB  - BACKGROUND: Arterial grafts for CABG have been used increasingly, and the radial
      artery (RA) has become a preferable graft, secondary to the internal mammary
      artery (IMA). In the present study, we investigated and compared NO release and
      endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization for
      IMA and RA. METHODS AND RESULTS: IMA and RA segments taken from CABG patients
      were placed in an organ chamber. An NO-sensitive electrode (to directly measure
      NO release) or intracellular glass microelectrode (to measure membrane potential)
      was used to study NO or EDHF in response to acetylcholine (ACh) and bradykinin
      (BK) before and after incubation with indomethacin (a cyclooxygenase inhibitor),
      N(G)-nitro-L-arginine (an NO synthase inhibitor), and oxyhemoglobin (an NO
      scavenger). The resting membrane potential of the smooth muscle cells of IMA and
      RA was -58+/-0.84 (n=61) and -61+/-1.3 (n=46) mV, respectively (P=0.03). BK
      induced EDHF-mediated hyperpolarization in the IMA was significantly greater than
      that in RA (BK 10(-)(7) mol/L: -10.9+/-1.5 [n=7] versus -5.8+/-0.9 [n=6] mV,
      P=0.04). The basal (16.8+/-1.9 versus 11.1+/-1.0 nmol/L, n=12, P=0.02) and
      stimulated releases of NO in IMA were significantly greater for BK (44.3+/-4.0
      versus 25.8+/-3.6 nmol/L, n=8, P=0.004) and lasting longer for ACh (9.5+/-2.0
      versus 6.6+/-3.6 minutes, n=12, P=0.03) than those in RA. CONCLUSIONS: The basal
      and stimulated releases of NO and EDHF-mediated hyperpolarization in the IMA are
      significantly greater than that in the RA. The lower capacity of NO release may
      contribute to the susceptibility of RA to the perioperative vasospasm and may
      have an impact on the long-term graft patency.

PMID- 11568081
TI  - Inhibition of tumor necrosis factor-alpha improves postischemic recovery of
      hypertrophied hearts.
AB  - BACKGROUND: Tumor necrosis factor (TNF)-alpha has been implicated in the
      pathogenesis of heart failure and ischemia-reperfusion injury. Effects of TNF
      alpha are initiated by membrane receptors coupled to sphingomyelinase signaling
      and include altered metabolism and calcium cycling, contractile dysfunction, and
      cell death. We postulate that pressure-overload hypertrophy results in increased
      myocardial TNF-alpha expression and that it contributes to decreased
      contractility in hypertrophied infant hearts subjected to ischemia-reperfusion.
      METHODS AND RESULTS: Neonatal rabbits underwent aortic banding to induce LV
      hypertrophy. Myocardial TNF-alpha protein expression increased progressively with
      LV hypertrophy. Serum TNF-alpha was detected only after the onset of heart
      failure. Before onset of ventricular dilatation and heart failure (determined by
      serial echocardiograms), hearts from aortic banded and age-matched control
      rabbits were perfused in the Langendorff mode and subjected to 45 minutes of
      ischemia and 30 minutes of reperfusion. Postischemic recovery was impaired in
      hypertrophied hearts, but addition of neutralizing anti-rabbit TNF-alpha antibody
      to cardioplegia and perfusate solutions restored postischemic function. This
      effect was mimicked by treatment with the ceramidase inhibitor N-oleoyl
      ethanolamine. TNF-alpha inhibition also was associated with faster postischemic
      recovery of phosphocreatine, ATP, and pH as assessed by (31)P nuclear magnetic
      resonance spectroscopy. Intracellular calcium handling, measured by Rhod 2
      spectrofluorometry, demonstrated lower diastolic calcium levels and higher
      systolic calcium transients in anti-TNF-alpha treated hearts. CONCLUSIONS: TNF
      alpha is expressed in myocardium during compensated pressure-overload hypertrophy
      and contributes to postischemic myocardial dysfunction. Inhibition of TNF-alpha
      signaling significantly improves postischemic contractile function, myocardial
      energetics, and intracellular calcium handling.

PMID- 11568082
TI  - Informed consent in clinical trials of in vitro diagnostic devices: perspectives
      from the FDA and manufacturers.

PMID- 11568083
TI  - Fluorescence-based, nonradioactive method for efficient detection of the
      pentanucleotide repeat (TTTTA)(n) polymorphism in the apolipoprotein(a) gene.
AB  - BACKGROUND: The apolipoprotein(a) [apo(a)] gene is a major predictor of plasma
      lipoprotein(a) concentrations, an independent risk factor for cardiovascular
      disease. The apo(a) gene contains a pentanucleotide repeat (PNR) polymorphism,
      1.4 kb upstream from the apo(a) gene reading frame. This polymorphism has been
      suggested to be important in control of apo(a) gene expression. METHODS: We
      developed a fluorescence-based, nonradioactive procedure to detect the PNR
      polymorphism. After amplification of the polymorphism by PCR, the respective PCR
      products were separated by denaturing polyacrylamide gel electrophoresis and
      detected using a 3'-end fluorescently labeled oligonucleotide as a probe. We used
      the method to characterize the PNR polymorphism pattern in 313 individuals, 195
      Caucasians and 118 African Americans. The new method efficiently separated DNAs
      corresponding to the different PNR repeats. RESULTS: Among both ethnic groups,
      alleles containing eight PNRs were most common. Smaller PNRs were more common
      among African Americans, and larger PNRs were more common among Caucasians.
      CONCLUSIONS: We developed a nonradioactive technique that separates the PNR
      polymorphism in the apo(a) gene and can be used in other studies involving
      closely sized polymorphisms.

PMID- 11568084
TI  - Hepatic carnitine palmitoyltransferase I deficiency: acylcarnitine profiles in
      blood spots are highly specific.
AB  - BACKGROUND: In carnitine palmitoyltransferase I (CPT-I) deficiency (MIM 255120),
      free carnitine can be increased with no pathologic acylcarnitine species
      detectable. As inclusion of CPT-I deficiency in high-risk and newborn screening
      could prevent potentially life-threatening complications, we tested whether CPT-I
      deficiency might be diagnosed by electrospray ionization-tandem mass spectrometry
      (ESI-MS/MS). METHODS: A 3.2-mm spot of whole blood dried on filter paper was
      extracted with 150 microL of methanol. After derivatization of carnitine and
      acylcarnitines to their butyl esters, the samples were analyzed by ESI-MS/MS with
      37.5 pmol of L-[(2)H(3)]carnitine and 7.5 pmol of L-[(2)H(3)]palmitoylcarnitine
      as internal standards. RESULTS: In all dried-blood specimens from each of three
      patients with CPT-I deficiency, we found an invariably increased ratio of free
      carnitine to the sum of palmitoylcarnitine and stearoylcarnitine [C0/(C16 +
      C18)]. The ratio in patients was between 175 and 2000, or 5- to 60-fold higher
      than the ratio for the 99.9th centile of the normal newborn population in Bavaria
      (n = 177 842). No overlap with the values of children that were known to be
      supplemented with carnitine was detected [C0/(C16 + C18), 34 +/- 30; mean +/- SD;
      n = 27]. CONCLUSIONS: ESI-MS/MS provides a highly specific acylcarnitine profile
      from dried-blood samples. The ratio of free carnitine to the sum of
      palmitoylcarnitine and stearoylcarnitine [C0/(C16 + C18)] is highly specific for
      CPT-I deficiency and may allow presymptomatic diagnosis.

PMID- 11568085
TI  - Comparison of Bio-Rad %CDT TIA and CDTect as laboratory markers of heavy alcohol
      use and their relationships with gamma-glutamyltransferase.
AB  - BACKGROUND: Carbohydrate-deficient transferrin (CDT) is used as a serum marker
      for heavy drinking. We compared a new Bio-Rad %CDT TIA assay with the CDTect
      assay; we also compared both to gamma-glutamyltransferase (GGT) as markers of
      heavy drinking. METHODS: Serum samples of well-defined alcoholics (n = 404) and
      matched (age, race, and gender) social drinkers (204) from 10 clinical centers
      were assayed with both CDT assays. Both assays use microcolumn separation after
      iron saturation, followed by enzyme immunoassay (CDTect) or turbidimetric
      immunoassay (Bio-Rad %CDT). In the latter, CDT is expressed as a percentage of
      total transferrin. RESULTS: The slope and intercept [95% confidence intervals
      (CIs)] for linear regression of results obtained by the %CDT-TIA (as percentage)
      and CDTect (units/L) assays were 0.091 (0.088-0.097) and 0.70% (0.54-0.86%),
      respectively (S(y/x) =1.30%; r = 0.848). The areas under the ROC curves (95% CIs)
      for CDTect and Bio-Rad %CDT TIA were 0.89 (0.86-0.92) and 0.88 (0.85-0.91),
      respectively, for men (P, not significant) and 0.76 (0.72-0.80) and 0.72 (0.68
      0.76) for women (P, not significant). When CDT (CDTect or Bio-Rad %CDT) was
      combined with GGT (either one positive), the clinical sensitivity in men was 90%
      for both assays, and specificities were 81% and 84%, respectively; sensitivities
      in women were 75% and 76%, respectively, and specificities were 87% and 91%.
      CONCLUSION: The new Bio-Rad %CDT TIA assay compares favorably to the widely
      studied CDTect assay in the detection of alcohol-use disorders.

PMID- 11568086
TI  - Tau and Abeta42 in cerebrospinal fluid from healthy adults 21-93 years of age:
      establishment of reference values.
AB  - BACKGROUND: Tau protein and the 42-amino acid form of beta-amyloid (Abeta42)
      measured in cerebrospinal fluid (CSF) have been proposed as potential biochemical
      diagnostic markers for Alzheimer disease. For the introduction of these assays in
      clinical practice, adequate reference values are of importance. METHODS: CSF
      samples were obtained from 231 neurologically and psychiatrically healthy
      individuals, 21-93 years of age, all with a MiniMental State examination score of
      28 or above. Standardized ELISAs were used to measure tau and Abeta42 in CSF.
      Following IFCC recommendations, we used a rank-based method; the 0.90 and 0.10
      fractiles were estimated to establish reference values for CSF-tau and CSF
      Abeta42, respectively. Putative confounding factors, such as the influence of the
      passage of proteins from peripheral blood to CSF, influence of dysfunction of the
      blood-brain barrier, and freezing and thawing of CSF, were investigated. RESULTS:
      A correlation with age was found for CSF-tau (r = 0.60; P <0.001). Therefore,
      separate reference values for different age groups were established for CSF-tau:
      <300 ng/L in the group 21-50 years of age, <450 ng/L in the group 51-70 years of
      age, and <500 ng/L in the group 71-93 years of age. CSF-Abeta42 did not correlate
      with age (r = -0.045), and the reference value was set to >500 ng/L. No
      correlation was found between blood-brain barrier function and CSF-tau or CSF
      Abeta42. CONCLUSIONS: These reference values can be applied when using CSF-tau
      and CSF-Abeta42 in clinical practice.

PMID- 11568087
TI  - Comparison of HPLC and small column (CDTect) methods for disialotransferrin.
AB  - BACKGROUND: Current methods for determination of carbohydrate-deficient
      transferrin (CDT) are based on separation of the CDT fraction by ion-exchange
      chromatography on minicolumns and quantification by immunoassay. Alternatively,
      the transferrin isoforms can be separated by HPLC anion-exchange chromatography
      and quantified by absorbance. This method has been reported to improve the
      validity of CDT as a marker of chronic alcohol abuse. METHODS: HPLC on either
      MonoQ or ResourceQ anion-exchange columns was used to separate and quantify
      isoforms of transferrin with detection at 460 nm. The result was expressed as the
      percentage of the disialo form (pI 5.7) of total transferrin (DST). The
      commercial CDTect assay was used as a comparison method. Serum samples from
      nondrinkers (n = 57), moderate drinkers (n = 77), and heavy drinkers (n = 139)
      were analyzed. RESULTS: In ROC analysis for differentiation between moderate and
      heavy drinkers, the area under the curve (AUC) for the HPLC method was 0.87 (95%
      confidence interval, 0.81-0.93), whereas that for CDTect was 0.72 (95% confidence
      interval, 0.64-0.80). At 90% specificity, the sensitivity of DST was 63% (95%
      confidence interval, 53-73%) compared with 33% (22-44%) for CDT. The reference
      interval of the HPLC method was 0.68-1.7%. CONCLUSIONS: The HPLC anion-exchange
      method for quantification of CDT provides substantially better separation between
      moderate and heavy drinkers than the CDTect method.

PMID- 11568088
TI  - Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its
      metabolites: correlation with plasma drug concentrations and effect of salivary
      pH.
AB  - BACKGROUND: Saliva is an alternative biologic matrix for drugs-of-abuse testing
      that offers the advantages of noninvasive, rapid, and easy sampling. We studied
      the excretion profile of 3,4-methylenedioxymethamphetamine (MDMA) and its
      metabolites in both saliva and plasma, as well the effect of the drug on salivary
      pH. METHODS: Saliva and plasma samples were obtained from eight healthy MDMA
      consumers after ingestion of a single 100-mg dose of the drug. Concentrations of
      MDMA and its main metabolites, 3,4-methylenedioxyamphetamine (MDA) and 4-hydroxy
      3-methoxymethamphetamine (HMMA), in saliva and plasma were measured by gas
      chromatography-mass spectrometry. Apparent pharmacokinetic parameters for MDMA in
      saliva were estimated, and the saliva-to-plasma ratio at each time interval was
      calculated and correlated with salivary pH. RESULTS: MDMA, MDA, and HMMA were
      detected in saliva. Salivary concentrations of MDMA were 1728.9-6510.6 microg/L
      and peaked at 1.5 h after drug intake. This was followed by a progressive
      decrease, with a mean concentration of 126.2 microg/L at 24 h. The saliva-to
      plasma ratio was 32.3-1.2, with a peak of 18.1 at 1.5 h after drug
      administration. Salivary pH seemed to be affected by MDMA administration; pH
      values decreased by 0.6 units (mean pH values of 6.9 and 6.8 at 1.5 and 4 h after
      drug administration vs predose pH of 7.4). CONCLUSIONS: Measurement of MDMA in
      saliva is a valuable alternative to determination of plasma drug concentrations
      in both clinical and toxicologic studies. On-site testing is also facilitated by
      noninvasive and rapid collection of salivary specimens.

PMID- 11568089
TI  - Atomic emission method for total boron in blood during neutron-capture therapy.
AB  - BACKGROUND: Boron neutron-capture therapy (BNCT) is a drug-targeted binary
      radiotherapy for cancer. The (10)B capture of thermal neutrons induces secondary
      radiation within cells during irradiation. The most widely used boron carrier is
      4-dihydroxyborylphenylalanine (BPA). The duration and timing of the irradiation
      is adjusted by monitoring (10)B concentrations in whole blood. METHODS: We
      developed a new method for boron determination that uses inductively coupled
      plasma atomic emission spectrometry (ICP-AES) and protein removal with
      trichloroacetic acid before analysis. This method was compared with the
      established but tedious inductively coupled plasma mass spectrometry (ICP-MS),
      which uses wet ashing as sample pretreatment. Erythrocyte boron concentrations
      were determined indirectly on the basis of plasma and whole blood boron
      concentrations and the hematocrit. The hematocrit was determined indirectly by
      measuring calcium concentrations in plasma and whole blood. RESULTS: Within- and
      between-day CVs were <5%. The recoveries for boron in whole blood were 95.6
      96.2%. A strong correlation was found between results of the ICP-AES and ICP-MS
      (r = 0.994). Marked differences in plasma and erythrocyte boron concentrations
      were observed during and after infusion of BPA fructose complex. CONCLUSIONS: The
      present method is feasible, accurate, and one of the fastest for boron
      determination during BNCT. Our results indicate that it is preferable to
      determine boron in plasma and in whole blood. Indirect erythrocyte-boron
      determination thus becomes possible and avoids the impact of preanalytical
      confounding factors, such as the influence of the hematocrit of the patient. Such
      an approach enables a more reliable estimation of the irradiation dose.

PMID- 11568090
TI  - Reference centiles for serum ferritin and percentage of transferrin saturation,
      with application to mutations of the HFE gene.
AB  - BACKGROUND: The gene that causes most cases of hereditary hemochromatosis is
      designated HFE. Individuals with mutations in the HFE gene may have increased
      serum iron, transferrin saturation, and ferritin concentrations relative to
      individuals with the wild-type genotype. METHODS: We generated reference centiles
      for percentage of transferrin saturation and serum ferritin concentrations in
      normal (wild-type), healthy Caucasian adults. We then examined transferrin and
      ferritin concentrations relative to these centiles in 81 individuals homozygous
      for the major hemochromatosis mutation C282Y and 438 individuals with the
      compound heterozygous HFE genotype C282Y/H63D. RESULTS: Serum ferritin
      concentrations, but not percentage of transferrin saturation, in normal, healthy
      women tended to increase sharply as they progressed through menopause.
      Transferrin and serum ferritin centiles for normal, healthy females were lower
      than the corresponding centiles in normal, healthy males. C282Y homozygotes had
      abnormally high transferrin saturation and serum ferritin values relative to the
      wild types. Compound heterozygotes appeared to be a mixture of individuals with
      unexceptional transferrin and ferritin values and those with abnormally large
      values similar to the homozygotes, with equal proportions of each. CONCLUSIONS:
      There are age- and sex-related differences in reference centiles for the
      percentage of transferrin saturation and serum ferritin concentrations in normal,
      healthy adults. Individuals homozygous for the C282Y mutation in the HFE gene
      have abnormal transferrin saturation and serum ferritin values relative to the
      reference population; penetrance with the compound heterozygotes, as reflected by
      abnormal transferrin and ferritin values, is less than with the homozygotes.

PMID- 11568091
TI  - Profiling of tryptophan-related plasma indoles in patients with carcinoid tumors
      by automated, on-line, solid-phase extraction and HPLC with fluorescence
      detection.
AB  - BACKGROUND: Profiling of the plasma indoles tryptophan, 5-hydroxytryptophan (5
      HTP), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) is useful in the
      diagnosis and follow-up of patients with carcinoid tumors. We describe an
      automated method for the profiling of these indoles in protein-containing
      matrices as well as the plasma indole concentrations in healthy controls and
      patients with carcinoid tumors. METHODS: Plasma, cerebrospinal fluid, and tissue
      homogenates were prepurified by automated on-line solid-phase extraction (SPE) in
      Hysphere Resin SH SPE cartridges containing strong hydrophobic polystyrene resin.
      Analytes were eluted from the SPE cartridge by column switching. Subsequent
      separation and detection were performed by reversed-phase HPLC combined with
      fluorometric detection in a total cycle time of 20 min. We obtained samples from
      14 healthy controls and 17 patients with metastasized midgut carcinoid tumors for
      plasma indole analysis. In the patient group, urinary excretion of 5-HIAA and
      serotonin was compared with concentrations of plasma indoles. RESULTS: Within-
      and between-series CVs for indoles in platelet-rich plasma were 0.6-6.2% and 3.7
      12%, respectively. Results for platelet-rich plasma serotonin compared favorably
      with those obtained by single-component analysis. Plasma 5-HIAA, but not 5-HTP
      was detectable in 8 of 17 patients with carcinoid tumors. In the patient group,
      platelet-rich plasma total tryptophan correlated negatively with platelet-rich
      plasma serotonin (P = 0.021; r = -0.56), urinary 5-HIAA (P = 0.003; r = -0.68),
      and urinary serotonin (P <0.0001; r = -0.80). CONCLUSIONS: The present
      chromatographic approach reduces analytical variation and time needed for
      analysis and gives more detailed information about metabolic deviations in indole
      metabolism than do manual, single-component analyses.

PMID- 11568092
TI  - Measurement of homocysteine and other aminothiols in plasma: advantages of using
      tris(2-carboxyethyl)phosphine as reductant compared with tri-n-butylphosphine.
AB  - BACKGROUND: Aminothiols have been implicated in the pathogenesis of
      arteriosclerosis, and reliable methods are needed to determine their
      concentrations in body fluids. We present a comparison of two analytical methods
      and focus on the reduction of low-molecular weight and protein-mixed disulfides
      of homocysteine, cysteine, cysteinyl-glycine, and glutathione. METHODS: The
      plasma total aminothiol profile was determined by HPLC with fluorescence
      detection after derivatization with ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4
      sulfonate. Disulfides and protein-bound aminothiols were reduced by either tri-n
      butylphosphine (the TBP method) or tris(2-carboxyethyl)phosphine (the TCEP
      method); the effects of temperature, time of reduction, and concentration of
      reductants were evaluated. RESULTS: The intraassay imprecision (CV) was <3% for
      all aminothiols using both methods. The interassay CVs for total cysteine (tCys),
      total cysteinyl-glycine (tCys-Gly), and total homocysteine (tHcy) were <4% and
      <8% for the TCEP and TBP methods, respectively, whereas for total glutathione
      (tGSH) the interassay CV was >12% for both methods. Deming regression and Bland
      Altman difference plots showed positive biases for total aminothiol
      concentrations determined by the TCEP method relative to the TBP method. The mean
      proportional biases were 65%, 27%, 6%, and 60% for tCys, tCys-Gly, tHcy, and
      tGSH, respectively. The calculated concentrations of total aminothiols by the
      TCEP method were less influenced by changes in temperature and concentration of
      reducing agent or by calibrator matrix. CONCLUSIONS: The agreement between the
      TCEP and TBP methods was considerably lower for the determination of tCys, tCys
      Gly, and tGSH than for tHcy. For total-aminothiol determination, the TCEP method
      yields better reproducibility and is more robust than the TBP method.

PMID- 11568093
TI  - Microvolume blood-sampling device with low hemolysis and high consistent yield of
      serum components.
AB  - BACKGROUND: Blood sampling by finger puncture is convenient, but the need for
      centrifugation and the problem of hemolysis remain, as does instability when
      samples must be shipped for analysis. We aimed to develop a blood-sampling device
      that provided high yields of serum with limited hemolysis and enabled
      preservation of serum components for at least 7 days at room temperature.
      METHODS: For separation of blood cells, we devised a grooved, asymmetric,
      polysulfonate membrane impregnated with sucrose. We evaluated hemoglobin (Hb)
      concentrations in the serum, assay values for 15 frequently measured serum
      components (including glucose), and the stability of analytes in the device.
      RESULTS: In sera from the new device, the Hb concentration was <or=0.43 mg/L.
      Recovered serum contained 65.0% +/- 4.2% (mean +/- SD; n = 41) of each of the
      serum components obtained by centrifugation. Serum components were stable in the
      device for 10 days at room temperature (25 degrees C). CONCLUSIONS: The newly
      developed device allows recovery of 60% of serum components from microvolumes of
      blood by finger puncture with neither degradation of analytes at room temperature
      nor hemolysis.

PMID- 11568094
TI  - Increased urinary S100B protein as an early indicator of intraventricular
      hemorrhage in preterm infants: correlation with the grade of hemorrhage.

PMID- 11568095
TI  - Optimal time interval between repeated blood sampling for measurements of total
      homocysteine in healthy individuals.

PMID- 11568096
TI  - Forty-eight hours of biopsy culture improve the sensitivity of the in vitro
      gliadin challenge in the diagnosis of celiac disease.

PMID- 11568097
TI  - Measurement of Indocyanine Green dye is improved by use of polyethylene glycol to
      reduce plasma turbidity.

PMID- 11568098
TI  - Total bilirubin measurement by photometry on a blood gas analyzer: potential for
      use in neonatal testing at the point of care.

PMID- 11568099
TI  - Effect of hemolyzed plasma on the batch measurement of nitrate by nitric oxide
      chemiluminescence.

PMID- 11568100
TI  - Components of total measurement error for hemoglobin A(1c) determination.

PMID- 11568101
TI  - Rapid and sensitive liquid chromatography-tandem mass spectrometry method for
      determination of monoethylglycinexylidide.

PMID- 11568102
TI  - Accuracy of fetal gender determination by analysis of DNA in maternal plasma.

PMID- 11568103
TI  - Cryoglobulins interfere with platelet counts by optical and impedance methods but
      not with the CD61 immunoplatelet count.

PMID- 11568104
TI  - Quantitative reverse transcription-PCR comparison of tumor cell enrichment
      methods.

PMID- 11568105
TI  - Quantification of copper in biological materials by use of electron spin
      resonance.

PMID- 11568106
TI  - Effects of long-term use of raloxifene, a selective estrogen receptor modulator,
      on thyroid function test profiles.

PMID- 11568107
TI  - Large amounts of cell-free fetal DNA are present in amniotic fluid.

PMID- 11568108
TI  - More than one-half of the erythroblasts in the fetal circulation and cord blood
      are TUNEL positive.

PMID- 11568109
TI  - Bioelectronic DNA chips for the clinical laboratory.

PMID- 11568110
TI  - Is sulfite an antiatherogenic compound in wine?

PMID- 11568111
TI  - Real-time PCR assay with fluorescent hybridization probes for rapid interleukin-6
      promoter (-174G-->C) genotyping.

PMID- 11568112
TI  - Rapid genotyping of the M129V polymorphism of prion protein using real-time
      fluorescent PCR.

PMID- 11568114
TI  - Age-dependent prevalence of vascular disease-associated polymorphisms among 2689
      volunteer blood donors.
AB  - BACKGROUND: The development of vascular disease involves the interaction of
      genetic and environmental factors. Because vascular disease is a major
      contributor to mortality in Western societies, we hypothesized that deleterious
      polymorphisms associated with hemostasis decrease in frequency among a healthy
      population as a function of age. METHODS: The frequencies of factor V G1691A
      Leiden (FVL), factor II (FII) G20210A, methylenetetrahydrofolate reductase
      (MTHFR) C677T, glycoprotein Ia (GPIa) C807T, glycoprotein IIIa (Pl(A1)/Pl(A2))
      T1565C, and angiotensin-converting enzyme (ACE) intron 16 insertion/deletion
      (I/D) alleles were determined among 2689 healthy Caucasian whole-blood donors.
      For analysis, participants were divided into three age groups: 17-39 years (n =
      979; 505 males and 474 females), 40-59 years (n = 900; 526 males and 374
      females), and 60-85 years (n = 810; 530 males and 280 females). RESULTS: The
      Pl(A2) allele frequency decreased from 17.5% to 15.7% and 14.1% in the 17-39
      years, 40-59 years, and 60-85 years age groups, respectively (n = 5094 alleles; P
      = 0.025). Among ACE DD males, the Pl(A2) allele frequency decreased from 20.8% to
      16.1% and 9.1% in the same groups, respectively (n = 810 alleles; P = 0.001). No
      statistically significant decrease in genotype or allele frequency was observed
      among carriers of FVL, FII 20210A, MTHFR 677T, GPIa 807T, or ACE D. CONCLUSIONS:
      These data suggest that Pl(A2) carriers, especially those who are ACE DD, are
      statistically less prevalent among older healthy blood donors compared with their
      younger counterparts. These observations suggest an important, deleterious, time
      dependent impact of the Pl(A2) allele, as well as the ACE DD/Pl(A2) allelic
      combination, on overall health and longevity.

PMID- 11568115
TI  - Use of up-converting phosphor reporters in lateral-flow assays to detect specific
      nucleic acid sequences: a rapid, sensitive DNA test to identify human
      papillomavirus type 16 infection.
AB  - BACKGROUND: A lateral-flow (LF) device using the new reporter up-converting
      phosphor technology (UPT) was applied to DNA (hybridization) assays for the
      detection of specific nucleic acid sequences, thereby aiming to perform the test
      outside well-equipped laboratories. The methodology reported here is sensitive
      and provides a rapid alternative for more elaborate gel electrophoresis and
      Southern blotting. In a preliminary study, it was applied to screen for the
      presence of human papillomavirus type 16 (HPV16) in a defined series of cervical
      carcinomas. METHODS: A LF assay was used to capture haptenized DNA molecules and
      hybrids, which were immunolabeled (before LF) with 400-nm UPT particles. These
      particles emit visible light after excitation with infrared in a process called
      up-conversion. Because up-conversion occurs in only the phosphor lattice,
      autofluorescence of other assay components is virtually nonexistent. RESULTS: The
      use of the UPT reporter in LF-DNA tests, as compared with colloidal gold,
      improved the detection limit at least 100-fold. UPT LF-DNA tests were
      successfully applied to detect (in a blind test) the presence of HPV16 in DNA
      extracts obtained from cervical carcinomas. Test results matched 100% with
      previous characterization of these carcinomas. CONCLUSIONS: The use of UPT in LF
      assays to detect specific nucleic acids provides low attamole-range sensitivity.
      Hybridization and consecutive detection of PCR-amplified HPV16 sequences were
      successful in a background of 10 microg of fish-sperm DNA. The sensitivity of UPT
      detection in these complex mixtures indicates that detection of viral infections
      without PCR or other amplification technique is achievable.

PMID- 11568116
TI  - Silicon-based biosensors for rapid detection of protein or nucleic acid targets.
AB  - BACKGROUND: We developed a silicon-based biosensor that generates visual,
      qualitative results or quantitative results for the detection of protein or
      nucleic acid targets in a multiplex format. METHODS: Capture probes were
      immobilized either passively or covalently on the optically coated surface of the
      biosensor. Intermolecular interactions of the immobilized capture probe with
      specific target molecules were transduced into a molecular thin film. Thin films
      were generated by enzyme-catalyzed deposition in the vicinity of the surface
      bound target. The increased thickness on the surface changed the apparent color
      of the biosensor by altering the interference pattern of reflected light.
      RESULTS: Cytokine detection was achieved in a 40-min multiplex assay. Detection
      limits were 4 ng/L for interleukin (IL)-6, 31 ng/L for IL1-beta, and 437 ng/L for
      interferon-gamma. In multianalyte experiments, cytokines were specifically
      detected with signal-to-noise ratios ranging from 15 to 80. With a modified
      optical surface, specificity was also demonstrated in a nucleic acid array with
      unambiguous discrimination of single-base changes in a 15-min assay. For
      homozygous wild-type and homozygous mutant samples, signal-to-noise ratios of
      approximately 100 were observed. Heterozygous samples yielded approximately
      equivalent signals for wild-type and mutant capture probes. CONCLUSIONS: The thin
      film biosensor allows rapid, sensitive, and specific detection of protein or
      nucleic acid targets in an array format with results read visually or quantified
      with a charge-coupled device camera. This biosensor is suited for multianalyte
      detection in clinical diagnostic assays.

PMID- 11568117
TI  - Proteomics in early detection of cancer.
AB  - Early detection is critical in cancer control and prevention. Biomarkers help in
      this process by providing valuable information about a the status of a cell at
      any given point in time. As a cell transforms from nondiseased to neoplastic,
      distinct changes occur that could be potentially detected through the
      identification of the appropriate biomarkers. Biomarker research has benefited
      from advances in technology such as proteomics. We discuss here ongoing research
      in this field, focusing on proteomic technologies. The advances in two
      dimensional electrophoresis and mass spectrometry are discussed in light of their
      contribution to biomarker research. Chip-based techniques, such as surface
      enhanced laser desorption, and ionization and emerging methods, such as tissue
      and antibody arrays, are also discussed. The development of bioinformatic tools
      that have and are being developed in parallel to proteomics is also addressed.
      This report brings into focus the efforts of the Early Detection Research Network
      at the National Cancer Institute in harnessing scientific expertise from leading
      institutions to identify and validate biomarkers for early detection and risk
      assessment.

PMID- 11568118
TI  - High-throughput genomic and proteomic analysis using microarray technology.
AB  - BACKGROUND: High-density microarrays are ideally suited for analyzing thousands
      of genes against a small number of samples. The next step in the discovery
      process is to take the resulting genes of interest and rapidly screen them
      against thousands of patient samples, tissues, or cell lines to further
      investigate their involvement in disease risk or the response to medication.
      METHODS: We used a microarray technology platform for both single-nucleotide
      polymorphisms (SNPs) and protein expression. Each microarray contains up to 250
      elements that can be customized for each application. Slides contained either a
      16- or 96-microarray format (4000-24,000 elements per slide), allowing the
      corresponding number of samples to be rapidly processed in parallel. RESULTS:
      Results for SNP genotyping and protein profiling agreed with results of
      restriction fragment length polymorphism (RFLP) analysis or ELISA, respectively.
      Genotyping analyses, using the microarray technology, on large sample sets over
      multiple polymorphisms in the NAT2 gene were in full agreement with traditional
      methodologies, such as sequencing and RFLP analysis. The multiplexed protein
      microarray had correlation coefficients of 0.82-0.99 (depending on analyte)
      compared with ELISAs. CONCLUSIONS: The integrated microarray technology platform
      is adaptable and versatile, while offering the high-throughput capabilities
      needed for drug development and discovery applications.

PMID- 11568128
TI  - Genome and hormones: an integrated approach to gender differences in physiology.

PMID- 11568129
TI  - Cytoskeletal regulation of pulmonary vascular permeability.
AB  - The endothelial cell (EC) lining of the pulmonary vasculature forms a
      semipermeable barrier between the blood and the interstitium of the lung.
      Disruption of this barrier occurs during inflammatory disease states such as
      acute lung injury and acute respiratory distress syndrome and results in the
      movement of fluid and macromolecules into the interstitium and pulmonary air
      spaces. These processes significantly contribute to the high morbidity and
      mortality of patients afflicted with acute lung injury. The critical importance
      of pulmonary vascular barrier function is shown by the balance between competing
      EC contractile forces, which generate centripetal tension, and adhesive cell-cell
      and cell-matrix tethering forces, which regulate cell shape. Both competing
      forces in this model are intimately linked through the endothelial cytoskeleton,
      a complex network of actin microfilaments, microtubules, and intermediate
      filaments, which combine to regulate shape change and transduce signals within
      and between EC. A key EC contractile event in several models of agonist-induced
      barrier dysfunction is the phosphorylation of regulatory myosin light chains
      catalyzed by Ca(2+)/calmodulin-dependent myosin light chain kinase and/or through
      the activity of the Rho/Rho kinase pathway. Intercellular contacts along the
      endothelial monolayer consist primarily of two types of complexes (adherens
      junctions and tight junctions), which link to the actin cytoskeleton to provide
      both mechanical stability and transduction of extracellular signals into the
      cell. Focal adhesions provide additional adhesive forces in barrier regulation by
      forming a critical bridge for bidirectional signal transduction between the actin
      cytoskeleton and the cell-matrix interface. Increasingly, the effects of
      mechanical forces such as shear stress and ventilator-induced stretch on EC
      barrier function are being recognized. The critical role of the endothelial
      cytoskeleton in integrating these multiple aspects of pulmonary vascular
      permeability provides a fertile area for the development of clinically important
      barrier-modulating therapies.

PMID- 11568130
TI  - Historical aspects of the early Soviet/Russian manned space program.
AB  - Human spaceflight was one of the great physiological and engineering triumphs of
      the 20th century. Although the history of the United States manned space program
      is well known, the Soviet program was shrouded in secrecy until recently.
      Konstantin Edvardovich Tsiolkovsky (1857-1935) was an extraordinary Russian
      visionary who made remarkable predictions about space travel in the late 19th
      century. Sergei Pavlovich Korolev (1907-1966) was the brilliant "Chief Designer"
      who was responsible for many of the Soviet firsts, including the first artificial
      satellite and the first human being in space. The dramatic flight of Sputnik 1
      was followed within a month by the launch of the dog Laika, the first living
      creature in space. Remarkably, the engineering work for this payload was all done
      in less than 4 wk. Korolev's greatest triumph was the flight of Yuri Alekseyevich
      Gagarin (1934-1968) on April 12, 1961. Another extraordinary feat was the first
      extravehicular activity by Aleksei Arkhipovich Leonov (1934-) using a flexible
      airlock that emphasized the entrepreneurial attitude of the Soviet engineers. By
      the mid-1960s, the Soviet program was overtaken by the United States program and
      attempts to launch a manned mission to the Moon failed. However, the early Soviet
      manned space program has a preeminent place in the history of space physiology.

PMID- 11568131
TI  - Postexercise muscle glycogen resynthesis in obese insulin-resistant Zucker rats.
AB  - We determined the effect of an acute bout of swimming (8 x 30 min) followed by
      either carbohydrate administration (0.5 mg/g glucose ip and ad libitum access to
      chow; CHO) or fasting (Fast) on postexercise glycogen resynthesis in soleus
      muscle and liver from female lean (ZL) and obese insulin-resistant (ZO) Zucker
      rats. Resting soleus muscle glycogen concentration ([glycogen]) was similar
      between genotypes and was reduced by 73 (ZL) and 63% (ZO) after exercise (P <
      0.05). Liver [glycogen] at rest was greater in ZO than ZL (334 +/- 31 vs. 247 +/-
      16 micromol/g wet wt; P < 0.01) and fell by 44 and 94% after exercise (P < 0.05).
      The fractional activity of glycogen synthase (active/total) increased immediately
      after exercise (from 0.22 +/- 0.05 and 0.32 +/- 0.04 to 0.63 +/- 0.08 vs. 0.57 +/
      0.05; P < 0.01 for ZL and ZO rats, respectively) and remained elevated above
      resting values after 30 min of recovery. During this time, muscle [glycogen] in
      ZO increased 68% with CHO (P < 0.05) but did not change in Fast. Muscle
      [glycogen] was unchanged in ZL from postexercise values after both treatments.
      After 6 h recovery, GLUT-4 protein concentration was increased above resting
      levels by a similar extent for both genotypes in both fasted (approximately 45%)
      and CHO-supplemented (approximately 115%) rats. Accordingly, during this time CHO
      refeeding resulted in supercompensation in both genotypes (68% vs. 44% for ZL and
      ZO). With CHO, liver [glycogen] was restored to resting levels in ZL but remained
      at postexercise values for ZO after both treatments. We conclude that the
      increased glucose availability with carbohydrate refeeding after glycogen
      depleting exercise resulted in glycogen supercompensation, even in the face of
      muscle insulin-resistance.

PMID- 11568132
TI  - Thermoregulatory and aerobic changes after endurance training in a hypobaric
      hypoxic and warm environment.
AB  - Plasma volume (PV) expansion by endurance training and/or heat acclimatization is
      known to increase aerobic and thermoregulatory capacities in humans. Also, higher
      erythrocyte volume (EV) fractions in blood are known to improve these capacities.
      We tested the hypothesis that training in a hypobaric hypoxic and warm
      environment would increase peak aerobic power (VO(2)(peak)) and forearm skin
      vascular conductance (FVC) response to increased esophageal temperature (T(es))
      more than training in either environment alone, by increasing both PV and EV.
      Twenty men were divided into four training regimens (n = 5 each): low-altitude
      cool (610-m altitude, 20 degrees C ambient temperature, 50% relative humidity),
      high-altitude cool (2,000 m, 20 degrees C), low-altitude warm (610 m, 30 degrees
      C), and high-altitude warm (HW; 2,000 m, 30 degrees C). They exercised on a cycle
      ergometer at 60% VO(2)(peak) for 1 h/day for 10 days in a climate chamber. After
      training, PV increased in all trials, but EV increased in only high-altitude
      trials (both P < 0.05). VO(2)(peak) increased in all trials (P < 0.05) but
      without any significant differences among trials. FVC response to increased T(es)
      was measured during exercise at 60% of the pretraining VO(2)(peak) at 610 m and
      30 degrees C. After the training, T(es) threshold for increasing FVC decreased in
      warm trials (P < 0.05) but not in cool trials and was significantly lower in HW
      than in cool trials (P < 0.05). The slope of FVC increase/T(es) increase
      increased in all trials (P < 0.05) except for high-altitude cool (P > 0.4) and
      was significantly higher in HW than in cool trials (P < 0.05). Thus, against our
      hypothesis, the VO(2)(peak) for HW did not increase more than in other trials.
      Moreover, slope of FVC increase/T(es) increase in HW increased most, despite the
      similar increase in blood volume, suggesting that factors other than blood volume
      were involved in the highest FVC response in HW.

PMID- 11568133
TI  - Dehydration and body fluid-regulating hormones during sweating in warm (38
      degrees C) fresh- and seawater immersion.
AB  - Body weight (BW) reductions of more than 4 kg have been observed during diving
      with the open hot water suit, a technique in which heated seawater (SW)
      continuously floods the skin surface. To test the hypothesis that osmotic effects
      may be involved in these fluid-loss processes, head-out immersion experiments in
      38 degrees C freshwater (FW) and SW for 4 h were performed. Average BW reduction
      was 2.5 and 1.9 kg in SW and FW head-out immersion, respectively (P < 0.01).
      Atrial natriuretic peptide increased during the first 30 min of SW immersion (5.6
      13.4 pmol/l, P < 0.01) followed by a reduction to 7.6 pmol/l (P < 0.01). This
      paralleled an initial decrease in aldosterone (from 427 to 306 pmol/l, P < 0.05)
      followed by an increase to 843 pmol/l (P < 0.01). The effects of temperature on
      fluid loss were studied in thermoneutral (34.5 degrees C) and 38 degrees C SW for
      2 h. In thermoneutral SW, calculated sweat production was negligible (0.05 kg)
      compared with 1.2 kg in warm SW. We recommend that, if a dive is planned to last
      for more than 4 h, a mandatory break for fluid intake should be incorporated in
      the diving regulations.

PMID- 11568134
TI  - Caffeine increases endurance and attenuates force sensation during submaximal
      isometric contractions.
AB  - Caffeine has known ergogenic effects, some of which have been observed during
      submaximal isometric contractions. We used 15 subjects in a randomized, double
      blind, repeated-measures experiment to determine caffeine's ergogenic effects on
      neuromuscular variables that would contribute to increased endurance capacity.
      Subjects performed repeated submaximal (50% maximal voluntary contraction)
      isometric contractions of the right quadriceps to the limit of endurance (T(lim))
      1 h after oral caffeine administration (6 mg/kg). Time to reach T(lim) increased
      by 17 +/- 5.25% (P < 0.02) after caffeine administration compared with the
      placebo trial. The changes in contractile properties, motor unit activation, and
      M-wave amplitude that occurred as the quadriceps reached T(lim) could not account
      for the prolonged performance after caffeine ingestion. In a separate experiment
      with the same subjects, we used a constant-sensation technique to determine
      whether caffeine influenced force sensation during 100 s of an isometric
      contraction of the quadriceps. The results of this experiment showed that
      caffeine reduced force sensation during the first 10-20 s of the contraction. The
      rapidity of this effect suggests that caffeine exerts its effects neurally. Based
      on these data, the caffeine-induced increase in T(lim) may have been caused by a
      willingness to maintain near-maximal activation longer because of alterations in
      muscle sensory processes.

PMID- 11568135
TI  - Glibenclamide improves postischemic recovery of myocardial contractile function
      in trained and sedentary rats.
AB  - In this study, we sought to determine whether there was any evidence for the idea
      that cardiac ATP-sensitive K+ (K(ATP)) channels play a role in the training
      induced increase in the resistance of the heart to ischemia-reperfusion (I/R)
      injury. To do so, the effects of training and an K(ATP) channel blocker,
      glibenclamide (Glib), on the recovery of left ventricular (LV) contractile
      function after 45 min of ischemia and 45 min of reperfusion were examined. Female
      Sprague-Dawley rats were sedentary (Sed; n = 18) or were trained (Tr; n = 17) for
      >20 wk by treadmill running, and the hearts from these animals used in a
      Langendorff-perfused isovolumic LV preparation to assess contractile function. A
      significant increase in the amount of 72-kDa class of heat shock protein was
      observed in hearts isolated from Tr rats. The I/R protocol elicited significant
      and substantial decrements in LV developed pressure (LVDP), minimum pressure
      (MP), rate of pressure development, and rate of pressure decline and elevations
      in myocardial Ca(2+) content in both Sed and Tr hearts. In addition, I/R elicited
      a significant increase in LV diastolic stiffness in Sed, but not Tr, hearts. When
      administered in the perfusate, Glib (1 microM) elicited a normalization of all
      indexes of LV contractile function and reductions in myocardial Ca(2+) content in
      both Sed and Tr hearts. Training increased the functional sensitivity of the
      heart to Glib because LVDP and MP values normalized more quickly with Glib
      treatment in the Tr than the Sed group. The increased sensitivity of Tr hearts to
      Glib is a novel finding that may implicate a role for cardiac K(ATP) channels in
      the training-induced protection of the heart from I/R injury.

PMID- 11568136
TI  - Exposure to hypoxia produces long-lasting sympathetic activation in humans.
AB  - The relative contributions of hypoxia and hypercapnia in causing persistent
      sympathoexcitation after exposure to the combined stimuli were assessed in nine
      healthy human subjects during wakefulness. Subjects were exposed to 20 min of
      isocapnic hypoxia (arterial O(2) saturation, 77-87%) and 20 min of normoxic
      hypercapnia (end-tidal P(CO)(2), +5.3-8.6 Torr above eupnea) in random order on 2
      separate days. The intensities of the chemical stimuli were manipulated in such a
      way that the two exposures increased sympathetic burst frequency by the same
      amount (hypoxia: 167 +/- 29% of baseline; hypercapnia: 171 +/- 23% of baseline).
      Minute ventilation increased to the same extent during the first 5 min of the
      exposures (hypoxia: +4.4 +/- 1.5 l/min; hypercapnia: +5.8 +/- 1.7 l/min) but
      declined with continued exposure to hypoxia and increased progressively during
      exposure to hypercapnia. Sympathetic activity returned to baseline soon after
      cessation of the hypercapnic stimulus. In contrast, sympathetic activity remained
      above baseline after withdrawal of the hypoxic stimulus, even though blood gases
      had normalized and ventilation returned to baseline levels. Consequently, during
      the recovery period, sympathetic burst frequency was higher in the hypoxia vs.
      the hypercapnia trial (166 +/- 21 vs. 104 +/- 15% of baseline in the last 5 min
      of a 20-min recovery period). We conclude that both hypoxia and hypercapnia cause
      substantial increases in sympathetic outflow to skeletal muscle. Hypercapnia
      evoked sympathetic activation is short-lived, whereas hypoxia-induced sympathetic
      activation outlasts the chemical stimulus.

PMID- 11568137
TI  - Effects of volatile anesthetics on stiffness of mammalian ventricular muscle.
AB  - To assess the effects of halothane, isoflurane, and sevoflurane on cross bridges
      in intact cardiac muscle, electrically stimulated (0.25 Hz, 25 degrees C) right
      ventricular ferret papillary muscles (n = 14) were subjected to sinusoidal load
      oscillations (37-182 Hz, 0.2-0.5 mN peak to peak) at the instantaneous self
      resonant frequency of the muscle-lever system. At resonance, stiffness is
      proportional to m * omega(2) (where m is equivalent moving mass and omega is
      angular frequency). Dynamic stiffness was derived by relating total stiffness to
      values of passive stiffness at each length during shortening and lengthening.
      Shortening amplitude and dynamic stiffness were decreased by halothane >
      isoflurane > or = sevoflurane. At equal peak shortening, dynamic stiffness was
      higher in halothane or isoflurane in high extracellular Ca(2+) concentration than
      in control. Halothane and isoflurane increased passive stiffness. The decrease in
      dynamic stiffness and shortening results in part from direct effects of volatile
      anesthetics at the level of cross bridges. The increase in passive stiffness
      caused by halothane and isoflurane may reflect an effect on weakly bound cross
      bridges and/or an effect on passive elastic elements.

PMID- 11568138
TI  - Protein kinase B/Akt activates c-Jun NH(2)-terminal kinase by increasing NO
      production in response to shear stress.
AB  - Laminar shear stress activates c-Jun NH(2)-terminal kinase (JNK) by the
      mechanisms involving both nitric oxide (NO) and phosphatidylinositide 3-kinase
      (PI3K). Because protein kinase B (Akt), a downstream effector of PI3K, has been
      shown to phosphorylate and activate endothelial NO synthase, we hypothesized that
      Akt regulates shear-dependent activation of JNK by stimulating NO production.
      Here, we examined the role of Akt in shear-dependent NO production and JNK
      activation by expressing a dominant negative Akt mutant (Akt(AA)) and a
      constitutively active mutant (Akt(Myr)) in bovine aortic endothelial cells
      (BAEC). As expected, pretreatment of BAEC with the PI3K inhibitor (wortmannin)
      prevented shear-dependent stimulation of Akt and NO production. Transient
      expression of Akt(AA) in BAEC by using a recombinant adenoviral construct
      inhibited the shear-dependent stimulation of NO production and JNK activation.
      However, transient expression of Akt(Myr) by using a recombinant adenoviral
      construct did not induce JNK activation. This is consistent with our previous
      finding that NO is required, but not sufficient on its own, to activate JNK in
      response to shear stress. These results and our previous findings strongly
      suggest that shear stress triggers activation of PI3K, Akt, and endothelial NO
      synthase, leading to production of NO, which (along with O(2-), which is also
      produced by shear) activates Ras-JNK pathway. The regulation of Akt, NO, and JNK
      by shear stress is likely to play a critical role in its antiatherogenic effects.

PMID- 11568139
TI  - PCO(2) threshold for CNS oxygen toxicity in rats in the low range of hyperbaric
      PO(2).
AB  - Central nervous system (CNS) oxygen toxicity, as manifested by the first
      electrical discharge (FED) in the electroencephalogram, can occur as convulsions
      and loss of consciousness. CO(2) potentiates this risk by vasodilation and pH
      reduction. We suggest that CO(2) can produce CNS oxygen toxicity at a PO(2) that
      does not on its own ultimately cause FED. We searched for the CO(2) threshold
      that will result in the appearance of FED at a PO(2) between 507 and 253 kPa.
      Rats were exposed to a PO(2) and an inspired PCO(2) in 1-kPa steps to define the
      threshold for FED. The results confirmed our assumption that each rat has its own
      PCO(2) threshold, any PCO(2) above which will cause FED but below which no FED
      will occur. As PO(2) decreased from 507 to 456, 405, and 355 kPa, the percentage
      of rats that exhibited FED without the addition of CO(2) (F(0)) dropped from 91
      to 62, to 8 and 0%, respectively. The percentage of rats (F) having FED as a
      function of PCO(2) was sigmoid in shape and displaced toward high PCO(2) with the
      reduction in PO(2). The following formula is suggested to express risk as a
      function of PCO(2) and PO(2) [abstract: see text] where P(50) is the PCO(2)for
      the half response and N is power. A small increase in PCO(2) at a PO(2) that does
      not cause CNS oxygen toxicity may shift an entire population into the risk zone.
      Closed-circuit divers who are CO(2)retainers or divers who have elevated inspired
      CO(2)are at increased risk of CNS oxygen toxicity.

PMID- 11568140
TI  - Influence of motoneuron firing synchronization on SEMG characteristics in
      dependence of electrode position.
AB  - The frequency content of the surface electromyography (SEMG) signal, expressed as
      median frequency (MF), is often assumed to reflect the decline of muscle fiber
      conduction velocity in fatigue. MF also decreases when motor unit firings
      synchronize, and we hypothesized that this effect can explain the electrode
      dependent pattern in our previous recordings from the trapezius muscle. An
      existing motoneuron (MN) model describes the afterhyperpolarization following a
      spike as an exponential function on which membrane noise is superimposed.
      Splitting the noise into a common and an individual component extended the model
      to a MN pool with a tunable level of firing synchrony. An analytical volume
      conduction model was used to generate motor unit action potentials to simulate
      SEMG. A realistic level of synchrony decreased the MF of the simulated bipolar
      SEMG by approximately 30% midway between endplate position and tendon but not
      above the endplate. This is in accordance with experimental data from the biceps
      brachii muscle. It was concluded that the pattern of decrease of MF during
      sustained contractions indeed reflects MN synchronization.

PMID- 11568141
TI  - A system to impose prescribed homogenous strains on cultured cells.
AB  - There is presently significant interest in cellular responses to physical forces,
      and numerous devices have been developed to apply stretch to cultured cells. Many
      of the early devices were limited by the heterogeneity of deformation of cells in
      different locations and by the high degree of anisotropy at a particular
      location. We have therefore developed a system to impose cyclic, large-strain,
      homogeneous stretch on a multiwell surface-treated silicone elastomer substrate
      plated with pulmonary epithelial cells. The pneumatically driven mechanism
      consists of four plates each with a clamp to fix one edge of the cruciform
      elastomer substrate. Four linear bearings set at predetermined angles between the
      plates ensure a constant ratio of principal strains throughout the stretch cycle.
      We present the design of the device and membrane shape, the surface modifications
      of the membrane to promote cell adhesion, predicted and experimental measurements
      of the strain field, and new data using cultured airway epithelial cells. We
      present for the first time the relationship between the magnitude of cyclic
      mechanical strain and the extent of wound closure and cell spreading.

PMID- 11568142
TI  - Effect of C-fiber-mediated, ozone-induced rapid shallow breathing on airway
      epithelial injury in rats.
AB  - We examined the relationship between C-fiber-mediated, ozone-induced rapid
      shallow breathing and airway epithelial cell injury at different airway sites
      within the lower respiratory tract of conscious Wistar rats (n = 24). We combined
      an acute 8-h ozone inhalation with vagal perineural capsaicin treatment, a
      selective C-fiber conduction block, and 5-bromo-2'-deoxyuridine (BrdU) labeling
      as an index of epithelial injury. Vehicle-treated rats that inhaled ozone
      developed a rapid shallow breathing pattern during ozone inhalation, whereas the
      capsaicin-treated rats that inhaled ozone showed no changes in respiratory
      frequency. In vehicle-treated, ozone-exposed rats that developed rapid shallow
      breathing, a progressive increase in BrdU-labeling density (no. of BrdU-labeled
      cells/mm(2) airway) was observed starting at the bifurcation of the left main
      stem bronchi (central airway) and going down either a short or long airway path.
      In vehicle-treated, ozone-exposed rats, terminal bronchioles supplied by short
      and long airway paths had a similar degree of BrdU-labeling density that was
      significantly (P < 0.05) greater than the BrdU-labeling density of the proximal
      airways that supply them. In contrast, the attenuation of rapid shallow breathing
      produced by capsaicin treatment resulted in a significantly reduced BrdU-labeling
      density in the terminal bronchioles supplied by short airway paths compared with
      the terminal bronchioles supplied by long airway paths. Our data indicate that
      ozone-induced rapid shallow breathing protects large conducting airways while
      producing a more even distribution of injury to terminal bronchioles.

PMID- 11568143
TI  - Nitric oxide and neurally mediated regulation of skin blood flow during local
      heating.
AB  - The mechanisms underlying the skin blood flow (SkBF) response to local heating
      are complex and poorly understood. Our goal was to examine the role of axon
      reflexes and nitric oxide (NO) in the SkBF response to a local heating protocol.
      We performed 40 experiments following a standardized heating protocol with
      different interventions, including blockade of the axon reflex (EMLA cream),
      antebrachial nerve blockade (0.5% bupivacaine injection), and NO synthase (NOS)
      inhibition (> or =10 mM N(G)-nitro-L-arginine methyl ester; microdialysis).
      Appropriate controls were performed to verify the efficacy of the various blocks.
      Values are expressed as a percentage of maximal SkBF (SkBF(max); 50 mM sodium
      nitroprusside). At the initiation of local heating, SkBF rose to an initial peak,
      followed by a brief nadir, and a secondary, progressive rise to a plateau. Axon
      reflex block decreased the initial peak from 75+3 to 32 +/- 2% SkBF(max) (P <
      0.01 vs. control) but did not affect the plateau. NOS inhibition before and
      throughout local heating reduced the initial peak from 75 +/- 3 to 56 +/- 3%
      SkBF(max) (P < 0.01) and the plateau from 87 +/- 4 to 40 +/- 5%. NOS inhibition
      during axon reflex block did not further reduce the initial SkBF peak compared
      with axon reflex block alone. Antebrachial nerve block did not affect the local
      heating SkBF response. The primary finding of these studies is that there are at
      least two independent mechanisms contributing to the rise in SkBF during
      nonpainful local heating: a fast-responding vasodilator system mediated by the
      axon reflexes and a more slowly responding vasodilator system that relies on
      local production of NO.

PMID- 11568144
TI  - Enhanced in vivo and in vitro contractile responses to beta(2)-adrenergic
      receptor stimulation in dogs susceptible to lethal arrhythmias.
AB  - The response to beta-adrenergic receptor (beta-AR) stimulation was evaluated in
      both isolated cardiomyocytes (video edge detection) and the intact animal
      (echocardiography) in dogs either susceptible (S) or resistant (R) to ventricular
      fibrillation induced by a 2-min coronary occlusion during the last minute of
      exercise. In the intact animal, velocity of circumferential fiber shortening
      (Vcf) was evaluated both before (n = 27, S = 12 and R = 15) and after myocardial
      infarction. Before infarction, increasing doses of isoproterenol provoked similar
      contractile and heart rate responses in each group of dogs. Either beta(1)-AR
      (bisoprolol) or beta(2)-AR (ICI-118551) antagonists reduced the isoproterenol
      response, with a larger reduction noted after the beta(1)-AR blockade. In
      contrast, after infarction, isoproterenol induced a significantly larger Vcf and
      heart rate response in the susceptible animals that was eliminated by beta(2)-AR
      blockade. The single-cell isotonic shortening response to isoproterenol (100 nM)
      was also larger in cells obtained from susceptible compared with resistant dogs
      and was reduced to a greater extent by beta(2)-AR blockade in the susceptible dog
      myocytes (S, -48%, n = 6; R, -15%, n = 9). When considered together, these data
      suggest that myocardial infarction provoked an enhanced beta(2)-AR response in
      susceptible, but not resistant, animals.

PMID- 11568145
TI  - Glycogen and glycogen phosphorylase associated with sarcoplasmic reticulum:
      effects of fatiguing activity.
AB  - The purpose of the present study was to investigate the effects of fatiguing
      muscular activity on glycogen, glycogen phosphorylase (GP), and Ca(2+) uptake
      associated with the sarcoplasmic reticulum (SR). Tetanic contractions (100 ms, 75
      Hz) of the gastrocnemius and plantaris muscles, elicited once per second for 15
      min, significantly reduced force to 26.5 +/- 4.0% and whole muscle glycogen to
      23% of rested levels. SR glycogen levels were 415.4 +/- 76.6 and 20.4 +/- 2.1
      microg/mg SR protein in rested and fatigued samples, respectively. The optical
      density of GP from SDS-PAGE was reduced to 21% of control, whereas pyridoxal 5'
      phosphate concentration, a quantitative indicator of GP content, was
      significantly reduced to 3% of control. GP activity after exercise, in the
      direction of glycogen breakdown, was reduced to 4% of control. Maximum SR Ca(2+)
      uptake rate was also significantly reduced to 81% of control. These data
      demonstrate that glycogen and GP associated with skeletal muscle SR are reduced
      after fatiguing activity.

PMID- 11568146
TI  - Enhanced lung C-fiber responsiveness in sensitized adult guinea pigs exposed to
      chronic tobacco smoke.
AB  - Tobacco smoke (TS) exposure induces bronchoconstriction and increases airway
      secretions and plasma extravasation in certain sensitive individuals,
      particularly those with asthma. C-fiber activation also induces these effects.
      Although the mechanism by which chronic TS exposure induces airway dysfunction is
      not well understood, TS exposure may enhance C-fiber responsiveness. To
      investigate the effect of chronic TS exposure on C-fiber responsiveness to
      capsaicin and bradykinin, especially in atopic individuals, we exposed ovalbumin
      (OA)-sensitized guinea pigs to TS (5 mg/l air, 30 min/day for 7 days/wk) or to
      compressed air. Nonsensitized guinea pigs were also exposed to either compressed
      air or TS. Beginning after 120 days of exposure, C fibers and rapidly adapting
      receptors (RARs) were challenged with capsaicin and bradykinin. TS exposure
      enhanced sensory receptor and airway responsiveness to both intravenous capsaicin
      and bradykinin challenge. C-fiber, RAR, and airway responsiveness to capsaicin
      challenge was greatest in OA-sensitized guinea pigs exposed to TS. OA alone
      induced capsaicin hyperresponsiveness at 5 microg. Airway responsiveness to
      bradykinin was also greatest in OA-sensitized guinea pigs exposed to TS. OA alone
      enhanced C-fiber responsiveness to bradykinin at 5 and 10 microg. C-fiber
      activation by either agonist appeared direct, whereas RAR activation appeared
      indirect. Therefore, a mechanism of airway hyperirritability induced by the
      combination of OA sensitization and chronic TS exposure may include
      hyperirritability of lung C fibers.

PMID- 11568147
TI  - Major role for neuronal NO synthase in curtailing choroidal blood flow
      autoregulation in newborn pig.
AB  - We examined whether nitric oxide (NO) generated from neuronal NO synthase (nNOS)
      contributes to the reduced ability of the newborn to autoregulate retinal blood
      flow (RBF) and choroidal blood flow (ChBF) during acute rises in perfusion
      pressure. In newborn pigs (1-2 days old), RBF (measured by microsphere) is
      autoregulated over a narrow range of perfusion pressure, whereas ChBF is not
      autoregulated. N(G)-nitro-L-arginine methyl ester (L-NAME) or specific nNOS
      inhibitors 7-nitroindazole, 3-bromo-7-nitroindazole, and 1-(2-trifluoromethyl
      phenyl)imidazole as well as ganglionic blocker hexamethonium, unveiled a ChBF
      autoregulation as observed in juvenile (4- to 6-wk old) animals, whereas
      autoregulation of RBF in the newborn was only enhanced by L-NAME. All NOS
      inhibitors and hexamethonium prevented the hypertension-induced increase in NO
      mediator cGMP in the choroid. nNOS mRNA expression and activity were three- to
      fourfold higher in the choroid of newborn pigs than in tissues of juvenile pigs.
      It is concluded that increased production of NO from nNOS curtails ChBF
      autoregulation in the newborn and suggests a role for the autonomic nervous
      system in this important hemodynamic function, whereas, for RBF autoregulation,
      endothelial NOS seems to exert a more important contribution in limiting
      autoregulation.

PMID- 11568148
TI  - Swim-trained rats have greater bone mass, density, strength, and dynamics.
AB  - Weight-bearing exercise is traditionally recommended for improving bone health in
      postmenopausal women. Effects of swim exercise were studied as an alternative to
      weight-bearing exercise in ovariectomized rats. Rats in a swim group (Sw, n = 8)
      swam for 12 wk, 5 days/wk for 60 min per session. A control group (Con, n = 9)
      engaged in no structured exercise. Femurs were analyzed for bone mineral density
      and for bone mineral content by dual energy X-ray absorptiometry, biomechanical
      properties by three-point bending (Instron), and bone structure and formation by
      histomorphometry. Food intake did not differ among groups. Final body weights
      were significantly lower in Sw compared with Con (P < 0.05). Swimmers had
      significantly greater femoral shaft bone mineral density and content (P < 0.05)
      compared with Con. Femurs of the Sw group had greater mechanical properties (P <
      0.05) compared with Con. Histomorphometric data were significantly better in the
      Sw group compared with Con after the 12-wk intervention (P < 0.05). In
      conclusion, data from this study demonstrate some beneficial effects of swim
      exercise on bone structure, turnover, and strength.

PMID- 11568149
TI  - Cellular adaptation to repeated eccentric exercise-induced muscle damage.
AB  - Eccentrically biased exercise results in skeletal muscle damage and stimulates
      adaptations in muscle, whereby indexes of damage are attenuated when the exercise
      is repeated. We hypothesized that changes in ultrastructural damage, inflammatory
      cell infiltration, and markers of proteolysis in skeletal muscle would come about
      as a result of repeated eccentric exercise and that gender may affect this
      adaptive response. Untrained male (n = 8) and female (n = 8) subjects performed
      two bouts (bout 1 and bout 2), separated by 5.5 wk, of 36 repetitions of
      unilateral, eccentric leg press and 100 repetitions of unilateral, eccentric knee
      extension exercises (at 120% of their concentric single repetition maximum), the
      subjects' contralateral nonexercised leg served as a control (rest). Biopsies
      were taken from the vastus lateralis from each leg 24 h postexercise. After bout
      2, the postexercise force deficit and the rise in serum creatine kinase (CK)
      activity were attenuated. Women had lower serum CK activity compared with men at
      all times (P < 0.05), but there were no gender differences in the relative
      magnitude of the force deficit. Muscle Z-disk streaming, quantified by using
      light microscopy, was elevated vs. rest only after bout 1 (P < 0.05), with no
      gender difference. Muscle neutrophil counts were significantly greater in women
      24 h after bout 2 vs. rest and bout 1 (P < 0.05) but were unchanged in men.
      Muscle macrophages were elevated in men and women after bout 1 and bout 2 (P <
      0.05). Muscle protein content of the regulatory calpain subunit remained
      unchanged whereas ubiquitin-conjugated protein content was increased after both
      bouts (P < 0.05), with a greater increase after bout 2. We conclude that
      adaptations to eccentric exercise are associated with attenuated serum CK
      activity and, potentially, an increase in the activity of the ubiquitin
      proteosome proteolytic pathway.

PMID- 11568150
TI  - Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip
      muscle ischemia in humans.
AB  - To identify whether muscle metaboreceptor stimulation alters baroreflex control
      of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood
      pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects
      in the supine position. Subjects performed 2 min of isometric handgrip exercise
      at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip
      muscle ischemia. During muscle ischemia, blood pressure was lowered and then
      raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine
      HCl, respectively. The slope of the relationship between MSNA and diastolic blood
      pressure was more negative (P < 0.001) during posthandgrip muscle ischemia (
      201.9 +/- 20.4 units. beat(-1). mmHg(-1)) when compared with control conditions (
      142.7 +/- 17.3 units. beat(-1). mmHg(-1)). No significant change in the slope of
      the relationship between heart rate and systolic blood pressure was observed.
      However, both curves shifted during postexercise ischemia to accommodate the
      elevation in blood pressure and MSNA that occurs with this condition. These data
      suggest that the sensitivity of baroreflex modulation of MSNA is elevated by
      muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of
      modulate heart rate is unchanged during posthandgrip muscle ischemia.

PMID- 11568151
TI  - Analysis of the harmonic content of the tidal flow waveforms in infants.
AB  - The aim of this study was to examine whether the spectral characteristics of
      tidal flow waveform reflect the interaction between the control of breathing and
      lung mechanics in 10 healthy infants (H), 10 infants with a history of wheezing
      disorders (W), and 10 infants with chronic lung disease (CLD). From the flow
      waveform, we calculated a shape index, the harmonic distortion (k(d)), which
      quantifies the extent to which a periodic signal deviates from a sine wave. The
      k(d) of the entire tidal flow waveform did not significantly discriminate between
      diagnostic groups. However, k(d) was sensitive to maturation: it increased from
      0.26 at 1 mo to 0.37 at 6 mo of age (P < 0.002). Furthermore, the frequency (f)
      spectra of the flow (V) amplitudes between 0.13 and 10 Hz followed a power law:
      V(f) approximately f(-s), where s (slope) is the exponent in the power law. The
      exponent of the healthy infants s(H) was 4.24 [95% confidence interval (CI) =
      0.2] at 1 mo, 4.39 (CI = 0.16) at 6 mo, and 4.35 (CI = 0.19) at 12 mo and not
      significantly changing with age. The mean value of s(W) was marginally lower
      (4.09 +/- 0.28; P < 0.05) than that of s(H). The mean s(CLD) was significantly
      lower (3.04 +/- 0.31; P < 0.001). Lower values of s and higher values of k(d)
      indicate an increased complexity of the feedback mechanisms determining tidal
      flow waveform and may be associated with disease.

PMID- 11568152
TI  - Ozone causes lipid peroxidation but little antioxidant depletion in exercising
      and nonexercising hamsters.
AB  - Ozone (O(3)), a major component of urban air pollution, is a strong oxidizing
      agent that can cause lung injury and inflammation. In the present study, we
      investigated the effect of inhalation of O(3) on levels of F(2)-isoprostanes in
      bronchoalveolar lavage fluid (BALF) and on levels of antioxidants in the BALF and
      plasma of hamsters. Because antioxidants, including urate, ascorbate, GSH, and
      vitamin E, defend the lungs by reacting with oxidizing agents, we expected to
      find a decrease in antioxidant levels after O(3) exposure. Similarly, we expected
      an increase in the levels of F(2)-isoprostanes, which are lipid peroxidation
      products. Exposure to 1.0 or 3.0 parts/million (ppm) O(3) for 6 h resulted in an
      increase in BALF neutrophil numbers, an indicator of acute inflammation, as well
      as elevation of BALF F(2)-isoprostanes. The higher dose of O(3) caused an
      increase in the BALF level of urate and a decrease in the plasma level of
      ascorbate, but 1.0 ppm O(3) had no effect on BALF or plasma antioxidant levels.
      Exposure to 0.12 ppm O(3) had no effect on BALF neutrophils or F(2)-isoprostanes
      nor on BALF and plasma antioxidants. We also investigated the effect of O(3)
      exposure of hamsters during exercise on F(2)-isoprostane and antioxidant levels.
      We found that exposure to 1.0 ppm O(3) during 1 h of exercise on a laddermill
      increased BALF levels of F(2)-isoprostanes but had no effect on BALF neutrophils
      or on BALF and plasma antioxidants. These results indicate that O(3) induces
      inflammation and biomolecule oxidation in the lungs, whereas extracellular
      antioxidant levels are relatively unchanged.

PMID- 11568153
TI  - Normovolemic hemodilution improves oxygen extraction capabilities in endotoxic
      shock.
AB  - We studied the effects of normovolemic hemodilution on tissue oxygen extraction
      capabilities in a canine model of endotoxic shock. Eighteen anesthetized and
      mechanically ventilated dogs underwent normovolemic hemodilution with 6%
      hydroxyethyl starch solution to reach hematocrit (Hct) levels around 40, 30, or
      20% before the administration of 2 mg/kg of Escherichia coli endotoxin. Cardiac
      tamponade was then induced by repeated injections of normal saline into the
      pericardial sac to reduce cardiac output and study whole body oxygen extraction
      capabilities. Whole body critical oxygen delivery was lower in the Hct 20% and
      30% groups (8.4 +/- 0.4 and 10.4 +/- 0.7 ml. kg(-1). min(-1), respectively) than
      in the Hct 40% group (12.8 +/- 0.8 ml. kg(-1). min(-1)) (both P < 0.005). The
      whole body critical oxygen extraction ratio was higher in the Hct 30% and 20%
      groups (49.1 +/- 8.2 and 55.2 +/- 4.6%, respectively) than in the Hct 40% group
      (37.1 +/- 4.4 %) (both P < 0.05). Liver critical oxygen extraction ratio was also
      higher in the Hct 30% and 20% groups than in the Hct 40% group. The arterial
      lactate concentrations and the gradient between ileum mucosal PCO(2) and arterial
      PCO(2) were lower in the Hct 20% and 30% groups than in the Hct 40% group. We
      conclude that, during an acute reduction in blood flow during endotoxic shock in
      dogs, normovolemic hemodilution is associated with improved tissue perfusion and
      increased oxygen extraction capabilities.

PMID- 11568154
TI  - Strenuous exercise decreases the percentage of type 1 T cells in the circulation.
AB  - Prolonged strenuous exercise is followed by a temporary functional immune
      impairment. Low numbers of CD4+ T helper (Th) and CD8+ T cytotoxic (Tc) cells are
      found in the circulation. These cells can be divided according to their cytokine
      profile into type 1 (Th1 and Tc1), which produce interferon-gamma and interleukin
      (IL)-2, and type 2 (Th2 and Tc2) cells, which produce IL-4. The question
      addressed in the present study was whether exercise affected the relative balance
      between the circulating levels of these cytokine-producing T cells. Nine male
      runners performed treadmill running for 2.5 h at 75% of maximal oxygen
      consumption. The intracellular expression of cytokines was detected following
      stimulation with ionomycin and phorbol 12-myristate 13-acetate in blood obtained
      before, during, and after exercise. The percentage of type 1 T cells in the
      circulation was suppressed at the end of exercise and 2 h after exercise, whereas
      no changes were found in the percentage of type 2 T cells. Plasma epinephrine
      correlated negatively with the percentage of circulating CD8+ T cells producing
      IL-2, whereas peak IL-6 correlated with the percentage of CD8+ IL-4-producing T
      cells in the circulation. Peak plasma IL-6 correlated with plasma cortisol
      postrunning. In conclusion, the postexercise decrease in T lymphocyte number is
      accompanied by a more pronounced decrease in type 1 T cells, which may be linked
      to high plasma epinephrine. Furthermore, IL-6 may stimulate type 2 T cells,
      thereby maintaining a relatively unaltered percentage of these cells in the
      circulation compared with total circulating lymphocyte number.

PMID- 11568155
TI  - Fastigial nucleus-mediated respiratory responses depend on the medullary
      gigantocellular nucleus.
AB  - Electrical stimulation of the rostral fastigial nucleus (FNr) alters respiration
      via activation of local neurons. We hypothesized that this FNr-mediated
      respiratory response was dependent on the integrity of the nucleus
      gigantocellularis of the medulla (NGC). Electrical stimulation of the FNr in 15
      anesthetized and tracheotomized spontaneously breathing rats significantly
      altered ventilation by 35.2 +/- 11.0% (P < 0.01) with the major effect being
      excitatory (78%). This respiratory response did not significantly differ from
      control after lesions of the NGC via bilateral microinjection of kainic or
      ibotenic acid (4.5 +/- 1.9%; P > 0.05) but persisted in sham controls. Eight
      other rats, in which horseradish peroxidase (HRP) solution was previously
      microinjected into the left NGC, served as nonstimulation controls or were
      exposed to either 15-min repeated electrical stimulation of the right FNr or
      hypercapnia for 90 min. Histochemical and immunocytochemical data showed that the
      right FNr contained clustered HRP-labeled neurons, most of which were double
      labeled with c-Fos immunoreactivity in both electrically and CO(2)-stimulated
      rats. We conclude that the NGC receives monosynaptic FNr inputs and is required
      for fully expressing FNr-mediated respiratory responses.

PMID- 11568156
TI  - Orthostasis fails to produce active limb venoconstriction in adolescents.
AB  - Orthostasis is characterized by translocation of blood from the upper body and
      thorax into dependent venous structures. Although active splanchnic
      venoconstriction is known to occur, active limb venoconstriction remains
      controversial. Based on prior work, we initially hypothesized that active
      venoconstriction does occur in the extremities during orthostasis in response to
      baroreflex activation. We investigated this hypothesis in the arms and legs of 11
      healthy volunteers, aged 13-19 yr, using venous occlusion strain gauge
      plethysmography to obtain the forearm and calf blood flows and to compute the
      capacitance vessel volume-pressure compliance relation. Subjects were studied
      supine and at -10, +20, and +35 degrees to load the baroreflexes. With +20
      degrees of tilt, blood flow decreased and limb arterial resistance increased
      significantly (P < 0.05) compared with supine. With +35 degrees of tilt, blood
      flow decreased, limb arterial resistance increased, and heart rate increased,
      indicating parasympathetic withdrawal and sympathetic activation with arterial
      vasoconstriction. The volume-pressure relation was unchanged by orthostatic
      maneuvers. The results suggest that active venoconstriction in the limbs is not
      important to mild orthostatic response.

PMID- 11568157
TI  - Transport properties of alveolar epithelium measured by molecular hetastarch
      absorption in isolated rat lungs.
AB  - To evaluate the transport properties of the alveolar epithelium, we instilled
      hetastarch (Het; 6%, 10 ml, 1 - 1 x 10(4) kDa) into the trachea of isolated rat
      lungs and then measured the molecular distribution of Het that entered the lung
      perfusate from the air space over 6 h. Het transport was driven by either
      diffusion or an oncotic gradient. Perfusate Het had a unique, bimodal molecular
      weight distribution, consisting of a narrow low-molecular-weight peak at 10-15
      kDa (range, 5-46 kDa) and a broad high-molecular-weight band (range 46-2,000 kDa;
      highest at 288 kDa). We modeled the low-molecular-weight transport as (passive)
      restricted diffusion or osmotic flow through a small-pore system and the high
      molecular-weight transport as passive transport through a large-pore system. The
      equivalent small-pore radius was 5.0 nm, with a distribution of 150 pores per
      alveolus. The equivalent large-pore radius was 17.0 nm, with a distribution of
      one pore per seven alveoli. The small-pore fluid conductivity (2 x 10(-5) ml. h(
      1). cm(-2). mmHg(-1)) was 10-fold larger than that of the large-pore
      conductivity.

PMID- 11568158
TI  - Determination of regional ventilation and perfusion in the lung using xenon and
      computed tomography.
AB  - We propose a model to measure both regional ventilation (V) and perfusion (Q) in
      which the regional radiodensity (RD) in the lung during xenon (Xe) washin is a
      function of regional V (increasing RD) and Q (decreasing RD). We studied five
      anesthetized, paralyzed, mechanically ventilated, supine sheep. Four 2.5-mm-thick
      computed tomography (CT) images were simultaneously acquired immediately cephalad
      to the diaphragm at end inspiration for each breath during 3 min of Xe breathing.
      Observed changes in RD during Xe washin were used to determine regional V and Q.
      For 16 mm(3), Q displayed more variance than V: the coefficient of variance of Q
      (CV(Q)) = 1.58 +/- 0.23, the CV of V (CV(V)) = 0.46 +/- 0.07, and the ratio of
      CV(Q) to CV(V) = 3.5 +/- 1.1. CV(Q) (1.21 +/- 0.37) and the ratio of CV(Q) to
      CV(V) (2.4 +/- 1.2) were smaller at 1,000-mm(3) scale, but CV(V) (0.53 +/- 0.09)
      was not. V/Q distributions also displayed scale dependence: log SD of V and log
      SD of Q were 0.79 +/- 0.05 and 0.85 +/- 0.10 for 16-mm(3) and 0.69 +/- 0.20 and
      0.67 +/- 0.10 for 1,000-mm(3) regions of lung, respectively. V and Q measurements
      made with CT and Xe also demonstrate vertically oriented and isogravitational
      heterogeneity, which are described using other methodologies. Sequential images
      acquired by CT during Xe breathing can be used to determine both regional V and Q
      noninvasively with high spatial resolution.

PMID- 11568159
TI  - Random walks, random sequences, and nonlinear dynamics in human optokinetic
      nystagmus.
AB  - Optokinetic nystagmus (OKN) is a reflexive eye movement with target-following
      slow phases (SP) alternating with oppositely directed fast phases (FP). We
      measured the following from OKN in three humans: FP beginning and ending
      positions, amplitudes, and intervals and SP amplitudes and velocities. We sought
      to predict future values of each parameter on the basis of past values, using
      state-space representation of the sequence (time-delay embedding) and local
      second-order approximation of trajectories. Predictability is an indication of
      determinism: this approach allows us to investigate the relative contributions of
      random and deterministic dynamics in OKN. FP beginning and ending positions
      showed good predictability, but SP velocity was less predictable. FP and SP
      amplitudes and FP intervals had little or no predictability. FP beginnings and
      endings were as predictable as randomized versions that retain linear
      autocorrelation; this is typical of random walks. Predictability of FP intervals
      did not change under random rearrangement, which is characteristic of a random
      process. Only linear determinism was demonstrated; nonlinear interactions may
      exist that would not be detected by our present approach.

PMID- 11568160
TI  - Lack of alpha(2)-adrenergic antilipolytic effect during exercise in subcutaneous
      adipose tissue of trained men.
AB  - The aim of this study was to investigate the involvement of the antilipolytic
      alpha(2)-adrenergic receptor pathway in the regulation of lipolysis during
      exercise in subcutaneous abdominal adipose tissue (SCAAT). Seven trained men and
      15 untrained men were studied. With the use of microdialysis, the extracellular
      glycerol concentration was measured in SCAAT at rest and during 60 min of
      exercise at 50% of maximal oxygen consumption. One microdialysis probe was
      perfused with Ringer solution; the other was supplemented with phentolamine
      (alpha(2)-adrenergic receptor antagonist). No differences in baseline
      extracellular or plasma glycerol concentrations were found between the two
      groups. The exercise-induced extracellular and plasma glycerol increase was
      higher in trained compared with untrained subjects (P < 0.05). Addition of
      phentolamine to the perfusate enhanced the exercise-induced response of
      extracellular glycerol in untrained subjects but not in trained subjects. The
      exercise-induced increase in plasma norepinephrine and epinephrine concentrations
      and the decrease in plasma insulin were not different in the two groups. These in
      vivo findings demonstrate higher exercise-induced lipolysis in trained compared
      with untrained subjects and show that, in trained subjects, the alpha(2)-mediated
      antilipolytic action is not involved in the regulation of lipolysis in SCAAT
      during exercise.

PMID- 11568161
TI  - Effects of hypoxia on alveolar fluid transport capacity in rat lungs.
AB  - There is little information regarding the effect of hypoxia on alveolar fluid
      clearance capacity. We measured alveolar fluid clearance, lung water volume,
      plasma catecholamine concentrations, and serum osmolality in rats exposed to 10%
      oxygen for up to 120 h and explored the mechanisms responsible for the increase
      in alveolar fluid clearance. The principal results were 1) alveolar fluid
      clearance did not change for 48 h and then increased between 72 and 120 h of
      exposure to hypoxia; 2) although nutritional impairment during hypoxia decreased
      basal alveolar fluid clearance, endogenous norepinephrine increased net alveolar
      fluid clearance; 3) the changes of lung water volume and serum osmolality were
      not associated with those of alveolar fluid clearance; 4) an administration of
      beta-adrenergic agonists further increased alveolar fluid clearance; and 5)
      alveolar fluid clearance returned to normal within 24 h of reoxygenation after
      hypoxia. In conclusion, alveolar epithelial fluid transport capacity increases in
      rats exposed to hypoxia. It is likely that a combination of endogenous
      norepinephrine and nutritional impairment regulates alveolar fluid clearance
      under hypoxic conditions.

PMID- 11568162
TI  - Influence of ribose on adenine salvage after intense muscle contractions.
AB  - The influence of ribose supplementation on skeletal muscle adenine salvage rates
      during recovery from intense contractions and subsequent muscle performance was
      evaluated using an adult rat perfused hindquarter preparation. Three minutes of
      tetanic contractions (60 tetani/min) decreased ATP content in the calf muscles by
      approximately 50% and produced an equimolar increase in IMP. Effective recovery
      of muscle ATP 1 h after contractions was due to reamination of IMP via the purine
      nucleotide cycle and was complete in the red gastrocnemius but incomplete in the
      white gastrocnemius muscle section. Adenine salvage rates in recovering muscle
      averaged 45 +/- 4, 49 +/- 5, and 30 +/- 3 nmol. h(-1). g(-1) for plantaris, red
      gastrocnemius, and white gastrocnemius muscle, respectively, which were not
      different from values in corresponding nonstimulated muscle sections. Adenine
      salvage rates increased five- to sevenfold by perfusion with approximately 4 mM
      ribose (212 +/- 17, 192 +/- 9, and 215 +/- 14 nmol. h(-1). g(-1) in resting
      muscle sections, respectively). These high rates were sustained in recovering
      muscle, except for a small (approximately 20%) but significant (P < 0.001)
      decrease in the white gastrocnemius muscle. Ribose supplementation did not affect
      subsequent muscle force production after 60 min of recovery. These data indicate
      that adenine salvage rates were essentially unaltered during recovery from
      intense contractions.

PMID- 11568163
TI  - Muscle glycogen depletion and subsequent replenishment affect anaerobic capacity
      of horses.
AB  - The purpose of this study was to determine the effect of muscle glycogen
      depletion and subsequent replenishment on anaerobic capacity of horses. In a
      blinded crossover study, seven fit horses performed glycogen-depleting exercise
      on two occasions. Horses were infused after glycogen-depleting exercise with
      either 6 g/kg body wt of glucose as a 13.5% solution in 0.9% NaCl (Glu) or with
      0.9% NaCl (Sal) of equivalent volume. Subsequently, horses performed a high-speed
      exercise test (120% of maximal rate of oxygen consumption) to estimate maximum
      accumulated oxygen deficit. Replenishment of muscle glycogen was greater (P <
      0.05) in Glu [from 24.7 +/- 7.2 (SE) to 116.5 +/- 7 mmol/kg wet wt before and
      after infusion, respectively] than in Sal (from 23.4 +/- 7.2 to 47.8 +/- 5.7
      mmol/kg wet wt before and after infusion, respectively). Run time to fatigue
      during the high-speed exercise test (97.3 +/- 8.2 and 70.8 +/- 8.3 s, P < 0.05),
      maximal accumulated oxygen deficit (105.7 +/- 9.3 and 82.4 +/- 10.3 ml O(2)
      equivalent/kg, P < 0.05), and blood lactate concentration at the end of the high
      speed exercise test (11.1 +/- 1.4 and 9.2 +/- 3.7 mmol/l, P < 0.05) were greater
      for Glu than for Sal, respectively. We concluded that decreased availability of
      skeletal muscle glycogen stores diminishes anaerobic power generation and
      capacity for high-intensity exercise in horses.

PMID- 11568164
TI  - Women at altitude: ventilatory acclimatization at 4,300 m.
AB  - Women living at low altitudes or acclimatized to high altitudes have greater
      effective ventilation in the luteal (L) compared with follicular (F) menstrual
      cycle phase and compared with men. We hypothesized that ventilatory
      acclimatization to high altitude would occur more quickly and to a greater degree
      in 1) women in their L compared with women in their F menstrual cycle phase, and
      2) in women compared with men. Studies were conducted on 22 eumenorrheic,
      unacclimatized, sea-level (SL) residents. Indexes of ventilatory acclimatization
      [resting ventilatory parameters, hypoxic ventilatory response, hypercapnic
      ventilatory response (HCVR)] were measured in 14 women in the F phase and in 8
      other women in the L phase of their menstrual cycle, both at SL and again during
      a 12-day residence at 4,300 m. At SL only, ventilatory studies were also
      completed in both menstrual cycle phases in 12 subjects (i.e., within-subject
      comparison). In these subjects, SL alveolar ventilation (expressed as end-tidal
      PCO(2)) was greater in the L vs. F phase. Yet the comparison between L- and F
      phase groups found similar levels of resting end-tidal PCO(2), hypoxic
      ventilatory response parameter A, HCVR slope, and HCVR parameter B, both at SL
      and 4,300 m. Moreover, these indexes of ventilatory acclimatization were not
      significantly different from those previously measured in men. Thus female
      lowlanders rapidly ascending to 4,300 m in either the L or F menstrual cycle
      phase have similar levels of alveolar ventilation and a time course for
      ventilatory acclimatization that is nearly identical to that reported in male
      lowlanders.

PMID- 11568165
TI  - Effects of neutrophil elastase inhibitor (ONO-5046) on lung injury after
      intestinal ischemia-reperfusion.
AB  - The underlying mechanisms of lung endothelial injury after intestinal ischemia
      reperfusion (I/R) injury are not fully known. Here we investigated the effects of
      posttreatment with a neutrophil elastase inhibitor (NEI; ONO-5046) on lung injury
      after intestinal I/R injury in a rat model. Intestinal I/R was produced by 90 min
      of ischemia followed by either 60 or 240 min of reperfusion. For all experimental
      groups, the endothelial permeability index increased, neutrophil H(2)O(2)
      production increased in the pulmonary vasculature blood, neutrophil counts
      increased in bronchoalveolar lavage fluid (BALF), and the cytokine-induced
      neutrophil chemoattractant (CINC)-1 and CINC-3 levels were increased in BALF
      after 240 min (P < 0.01). In rats treated with NEI from 60 min after reperfusion,
      the lung endothelial permeability index was significantly reduced (P < 0.05),
      whereas neutrophil H(2)O(2) production in pulmonary vasculature blood and
      neutrophil count in BALF were significantly suppressed by NEI (P < 0.05 and P <
      0.01, respectively). In addition, NEI significantly suppressed the increase of
      CINC-1 and CINC-3 levels in BALF (P < 0.05). Our study clearly indicates that
      posttreatment with NEI reduces neutrophil activation in the pulmonary vessels and
      neutrophil accumulation in the lungs and suggests that ONO-5046, even when
      administered after the primary intestinal insult, can prevent the progression of
      lung injury associated with intestinal I/R.

PMID- 11568166
TI  - TGF-beta(1) gene-race interactions for resting and exercise blood pressure in the
      HERITAGE Family Study.
AB  - We examined the possible association between a transforming growth factor (TGF)
      beta(1) gene polymorphism in codon 10 and blood pressure (BP) at rest, in acute
      response to exercise in the pretrained (sedentary) and trained states, as well as
      in its training response (Delta) to 20 wk of endurance exercise. Subjects were
      257 black and 480 white, healthy sedentary normotensive subjects from the
      HERITAGE Family Study. The polymorphism was detected by polymerase chain reaction
      and digestion with the Msp A1 I endonuclease yielding a wild (leucine-10) and a
      mutant (proline-10) allele. Resting and exercise [50 W plus 60, 80, and 100%
      maximal oxygen consumption (VO(2)(max))] BP were determined before and after
      training. Significant (P < 0.05) race-genotype interactions were found for
      systolic (S) BP in both the sedentary and trained states. Among whites but not in
      blacks, the TGF-beta(1) genotypes were significantly (P < 0.05) associated with
      sedentary-state SBP at rest, at 50 W, and at 60 and 100% VO(2)(max)as well as
      with trained-state SBP at rest and at 80 and 100% VO(2)(max). The leucine-10
      homozygotes had significantly (P < 0.05) lower SBP than proline-10 homozygotes.
      DeltaBP was not significantly associated with genotype. These results support the
      hypothesis of an association between the TGF-beta(1) marker in codon 10 and SBP
      at rest and in response to acute exercise in whites but not in blacks.

PMID- 11568167
TI  - Decreased non-MHC-restricted (CD56+) killer cell cytotoxicity after spaceflight.
AB  - Cytotoxic activity of non-major histocompatibility complex-restricted (CD56+)
      (NMHC) killer cells and cell surface marker expression of peripheral blood
      mononuclear cells were determined before and after spaceflight. Ten astronauts (9
      men, 1 woman) from two space shuttle missions (9- and 10-day duration)
      participated in the study. Blood samples were collected 10 days before launch,
      within 3 h after landing, and 3 days after landing. All peripheral blood
      mononuclear cell preparations were cryopreserved and analyzed simultaneously in a
      4-h cytotoxicity (51)Cr release assay using K562 target cells. NMHC killer cell
      lytic activity was normalized per 1,000 CD56+ cells. When all 10 subjects were
      considered as one study group, NMHC killer cell numbers did not change
      significantly during the three sampling periods, but at landing lytic activity
      had decreased by approximately 40% (P < 0.05) from preflight values. Nine of ten
      astronauts had decreased lytic activity immediately after flight. NMHC killer
      cell cytotoxicity of only three astronauts returned toward preflight values by 3
      days after landing. Consistent with decreased NMHC killer cell cytotoxicity,
      urinary cortisol significantly increased after landing compared with preflight
      levels. Plasma cortisol and ACTH levels at landing were not significantly
      different from preflight values. No correlation of changes in NMHC killer cell
      function or hormone levels with factors such as age, gender, mission, or
      spaceflight experience was found. After landing, expression of the major
      lymphocyte surface markers (CD3, CD4, CD8, CD14, CD16, CD56), as determined by
      flow cytometric analysis, did not show any consistent changes from measurements
      made before flight.

PMID- 11568168
TI  - PI3-kinase/Akt modulates vascular smooth muscle tone via cAMP signaling pathways.
AB  - Phosphatidylinositol 3-kinase (PI3-kinase) activates protein kinase B (also known
      as Akt), which phosphorylates and activates a cyclic nucleotide phosphodiesterase
      3B. Increases in cyclic nucleotide concentrations inhibit agonist-induced
      contraction of vascular smooth muscle. Thus we hypothesized that the PI3
      kinase/Akt pathway may regulate vascular smooth muscle tone. In unstimulated,
      intact bovine carotid artery smooth muscle, the basal phosphorylation of Akt was
      higher than that in cultured smooth muscle cells. The phosphorylation of Akt
      decreases in a time-dependent manner when incubated with the PI3-kinase
      inhibitor, LY-294002. Agonist (serotonin)-, phorbol ester (phorbol 12,13
      dibutyrate; PDBu)-, and depolarization (KCl)-induced contractions of vascular
      smooth muscles were all inhibited in a dose-dependent fashion by LY-294002.
      However, LY-294002 did not inhibit serotonin- or PDBu-induced increases in myosin
      light chain phosphorylation or total O(2) consumption, suggesting that inhibition
      of contraction was not mediated by reversal or inhibition of the pathways that
      lead to smooth muscle activation and contraction. Treatment of vascular smooth
      muscle with LY-294002 increased the activity of cAMP-dependent protein kinase and
      increased the phosphorylation of the cAMP-dependent protein kinase substrate heat
      shock protein 20 (HSP20). These data suggest that activation of the PI3
      kinase/Akt pathway in unstimulated smooth muscle may modulate vascular smooth
      muscle tone (allow agonist-induced contraction) through inhibition of the cyclic
      nucleotide/HSP20 pathway and suggest that cyclic nucleotide-dependent inhibition
      of contraction is dissociated from the myosin light chain contractile regulatory
      pathways.

PMID- 11568169
TI  - Effects of ovariectomy and estrogen on ischemia-reperfusion injury in hindlimbs
      of female rats.
AB  - The effects of estrogen and ovariectomy on indexes of muscle damage after 2 h of
      complete hindlimb ischemia and 2 h of reperfusion were investigated in female
      Sprague-Dawley rats. The rats were assigned to one of three experimental groups:
      ovariectomized with a 17beta-estradiol pellet implant (OE), ovariectomized with a
      placebo pellet implant (OP), or control with intact ovaries (R). It was
      hypothesized that following ischemia-reperfusion (I/R), muscle damage indexes
      [serum creatine kinase (CK) activity, calpain-like activity, inflammatory cell
      infiltration, and markers of lipid peroxidation (thiobarbituric-reactive
      substances)] would be lower in the OE and R rats compared with the OP rats due to
      the protective effects of estrogen. Serum CK activity following I/R was greater
      (P < 0.01) in the R rats vs. OP rats and similar in the OP and OE rats. Calpain
      like activity was greatest in the R rats (P < 0.01) and similar in the OP and OE
      rats. Neutrophil infiltration was assessed using the myeloperoxidase (MPO) assay
      and immunohistochemical staining for CD43-positive (CD43+) cells. MPO activity
      was lower (P < 0.05) in the OE rats compared with any other group and similar in
      the OP and R rats. The number of CD43+ cells was greater (P < 0.01) in the OP
      rats compared with the OE and R rats and similar in the OE and R rats. The OE
      rats had lower (P < 0.05) thiobarbituric-reactive substance content following I/R
      compared with the R and OP rats. Indexes of muscle damage were consistently
      attenuated in the OE rats but not in the R rats. A 10-fold difference in serum
      estrogen content may mediate this. Surprisingly, serum CK activity and muscle
      calpain-like activity were lower (P < 0.05) in the OP rats compared with the R
      rats. Increases in serum insulin-like growth factor-1 content (P < 0.05) due to
      ovariectomy were hypothesized to account for this finding. Thus both ovariectomy
      and estrogen supplementation have differential effects on indexes of I/R muscle
      damage.

PMID- 11568170
TI  - Comparison of lung protection strategies using conventional and high-frequency
      oscillatory ventilation.
AB  - This study compared pathophysiological and biochemical indexes of acute lung
      injury in a saline-lavaged rabbit model with different ventilatory strategies: a
      control group consisting of moderate tidal volume (V(T)) (10-12 ml/kg) and low
      positive end-expiratory pressure (PEEP) (4-5 cmH(2)O); and three protective
      groups: 1) low V(T) (5-6 ml/kg) high PEEP, 2-3 cmH(2)O greater than the lower
      inflection point; 2) low V(T) (5-6 ml/kg), high PEEP (8-10 cmH(2)O); and 3) high
      frequency oscillatory ventilation (HFOV). The strategy using PEEP > inflection
      point resulted in hypotension and barotrauma. HFOV attenuated the decrease in
      pulmonary compliance, the lung inflammation assessed by polymorphonuclear
      leukocyte infiltration and tumor necrosis factor-alpha concentration in the
      alveolar space, and pathological changes of the small airways and alveoli.
      Conventional mechanical ventilation using lung protection strategies (low V(T)
      high PEEP) only attenuated the decrease in oxygenation and pulmonary compliance.
      Therefore, HFOV may be a preferable option as a lung protection strategy.

PMID- 11568171
TI  - Local perfusion and metabolic demand during exercise: a noninvasive MRI method of
      assessment.
AB  - A noninvasive magnetic resonance imaging (MRI) method to assess the distribution
      of perfusion and metabolic demand (Q/VO(2)) in exercising human skeletal muscle
      is described. This method combines two MRI techniques that can provide accurate
      multiple localized measurements of Q/VO(2) during steady-state plantar flexion
      exercise. The first technique, (31)P chemical shift imaging, permits the
      acquisition of comparable phosphorus spectra from multiple voxels simultaneously.
      Because phosphocreatine (PCr) depletion is directly proportional to ATP
      hydrolysis, its relative depletion can be used as an index of muscle O(2) uptake
      (VO(2)). The second MRI technique allows the measurement of both spatially and
      temporally resolved muscle perfusion in vivo by using arterial spin labeling.
      Promising validity and reliability data are presented for both MRI techniques.
      Initial results from the combined method provide evidence of a large variation in
      Q/VO(2), revealing areas of apparent under- and overperfusion for a given
      metabolic turnover. Analysis of these data in a similar fashion to that employed
      in the assessment of ventilation-to-perfusion matching in the lungs revealed a
      similar second moment of the perfusion distribution and PCr distribution on a log
      scale (log SD(Q) and log SD(PCr)) (0.47). Modeling the effect of variations in
      log SD(Q) and log SD(PCr) in terms of attainable VO(2), assuming no diffusion
      limits, indicates that the log SD(Q) and log SD(PCr) would allow only 92% of the
      target VO(2) to be achieved. This communication documents this novel, noninvasive
      method for assessing Q/VO(2), and initial data suggest that the mismatch in
      Q/VO(2) may play a significant role in determining O(2) transport and utilization
      during exercise.

PMID- 11568172
TI  - An abridged history of sex steroid hormone receptor action.
AB  - The field of steroid hormone action is well established, although it is barely
      more than four decades old. Pivotal experiments in the late 1950s and 1960s
      showed that hormone-binding components exist within nuclei of target tissues and
      that steroid hormones act by regulating gene expression, rather than directly
      influencing enzymatic processes. The understanding that steroid hormone receptors
      interact with the general transcription machinery and alter chromatin structure
      came in the 1970s and 1980s, and details of this mechanism continue to be
      elucidated. In addition, the discovery of rapid cellular responses to steroid
      hormones has led to the identification of putative membrane-bound steroid
      receptors that act without affecting gene transcription. As noted in the recent
      Institute of Medicine report "Exploring the Biological Contributions to Human
      Health: Does Sex Matter?", the effects of steroid hormones and defects in steroid
      hormone receptor action have a profound impact on human health and disease.
      Future research directives include the development of potent, selective steroid
      receptor modulators, the elucidation of nongenomic steroid hormone effects, and
      further exploration of hormone-genome interactions.

PMID- 11568173
TI  - Cell localization, physiology, and nongenomic actions of estrogen receptors.
AB  - The existence of binding proteins for the female sex steroid, 17beta-estradiol,
      has been known for almost 50 years. Presently, two estrogen receptors (ERs), ER
      alpha and ER-beta, have been cloned in mammals, and they are expressed in many
      cell types of metazoans. ERs act primarily as nuclear transcription factors, and
      this effect is enhanced by ligand binding. Emerging data have identified a
      separate pool of receptors for this steroid in the plasma membrane, but the
      mechanisms of action and cellular functions of these proteins are just beginning
      to be defined. In this review, the known details of the nuclear and plasma
      membrane ER functions will be discussed. A particular focus will be to define the
      signaling pathways from the membrane that lead to important cell physiology
      effects of estrogen. The potential interactions of membrane ER with other local
      proteins will also be discussed, and the unique but often complementary roles of
      the receptor pools will be highlighted. These details may be of additional
      relevance to other steroid receptors, since there is evidence of their existence
      in the cell membrane.

PMID- 11568174
TI  - Cardiovascular protective effects of 17beta-estradiol metabolites.
AB  - 17beta-estradiol (estradiol), the most abundant endogenous estrogen, affords
      cardiovascular protection. However, in a given cohort of postmenopausal women,
      estradiol replacement therapy provides cardiovascular protection in only a
      subset. The reasons for this variable action can only be understood once the
      mechanisms by which estradiol induces its cardiovascular protective effects are
      known. Because most biological effects of estradiol are mediated via estrogen
      receptors (ERs) and the heart and blood vessels contain both ER-alpha and ER
      beta, the prevailing view is that ERs mediate estradiol-induced cardiovascular
      protection. However, recent findings that estradiol protects against vascular
      injury in arteries of mice lacking either ER-alpha or ER-beta seriously
      challenges this concept. Thus other non-ER mechanisms may be operative.
      Endogenous estradiol is enzymatically converted to several nonestrogenic
      metabolites, and some of these metabolites induce potent biological effects via
      ER-independent mechanisms. Therefore, it is conceivable that the cardiovascular
      protective effects of estradiol are mediated via its endogenous metabolites. On
      the basis of the evidence cited in this review, the cardiovascular protective
      effects of estradiol are both ER dependent and independent. The purpose of this
      article is to review the evidence regarding the cardiovascular protective effects
      of estradiol metabolites and to discuss the cellular, biochemical, and molecular
      mechanisms involved.

PMID- 11568176
TI  - Estrogen receptor-alpha antisense decreases brain estrogen receptor levels and
      affects ventilation in male and female rats.
AB  - We hypothesized that administration of an antisense oligodeoxynucleotide (ODN) to
      estrogen receptor (ER)-alpha mRNA decreases the ER protein in the neonatal rat
      brain, alters the sex-specific ventilatory responses to aspartic acid in rats,
      and counteracts the effects of testosterone proportionate (TP) in females. One
      day-old rat pups were injected intraventricularly with vehicle, antisense ER ODN,
      or scrambled ODN control. Additional groups of females received TP or vehicle and
      one of the three treatments. Brain ER protein levels were decreased by 65% at 6 h
      and 35% at 24 h after antisense ODN. Aspartic acid decreased ventilation in all
      groups of weanling males and females except ER ODN-treated females and TP-vehicle
      treated females. Aspartic acid decreased ventilation in all groups of adult
      females except those given TP and in males. Weanling ER ODN-treated rats were
      shorter and weighed less than controls. Only adult ER ODN-treated males exhibited
      these traits. Thus neonatal ER affects aspartic acid modulation of breathing and
      body growth in a sex-specific and developmental manner.

PMID- 11568177
TI  - Sex differences in osmotic regulation of AVP and renal sodium handling.
AB  - To determine sex differences in osmoregulation of arginine vasopressin (AVP) and
      body water, we studied eight men (24 +/- 1 yr) and eight women (29 +/- 2 yr)
      during 3% NaCl infusion [hypertonic saline infusion (HSI); 120 min, 0.1 ml. kg
      body wt(-1). min(-1)]. Subjects then drank 15 ml/kg body wt over 30 min followed
      by 60 min of rest. Women were studied in the early follicular (F; 16.1 +/- 2.8
      pg/ml plasma 17beta-estradiol and 0.6 +/- 0.1 ng/ml plasma progesterone) and
      midluteal (L; 80.6 +/- 11.4 pg/ml plasma 17beta-estradiol and 12.7 +/- 0.7 ng/ml
      plasma progesterone) menstrual phases. Basal plasma osmolality was higher in F
      (286 +/- 1 mosmol/kgH(2)O) and in men (289 +/- 1 mosmol/kgH(2)O) compared with L
      (280 +/- 1 mosmol/kgH(2)O, P < 0.05). Neither menstrual phase nor gender affected
      basal plasma AVP concentration (P([AVP]); 1.7 +/- 4, 1.9 +/- 0.4, and 2.2 +/- 0.5
      pg/ml for F, L, and men, respectively). The plasma osmolality threshold for AVP
      release was lowest in L (x-intercept, 263 +/- 3 mosmol/kgH(2)O, P < 0.05)
      compared with F (273 +/- 2 mosmol/kgH(2)O) and men (270 +/- 4 mosmol/kgH(2)O)
      during HSI. Men had greater P([AVP])-plasma osmolality slopes (i.e., sensitivity)
      compared with F and L (slopes = 0.14 +/- 0.04, 0.09 +/- 0.01, and 0.24 +/- 0.07
      for F, L, and men, respectively, P < 0.05). Despite similar Na+-regulating
      hormone responses, men excreted less Na+ during HSI (0.7 +/- 0.1, 0.7 +/- 0.1,
      and 0.5 +/- 0.1 meq/kg body wt for F, L, and men, respectively, P < 0.05).
      Furthermore, men had greater systolic blood pressure (119 +/- 5, 119 +/- 5, and
      132 +/- 3 mmHg for F, L, and men, respectively, P < 0.05) than F and L. Our data
      indicate greater sensitivity in P([AVP]) response to changes in plasma osmolality
      as the primary difference between men and women during HSI. In men, this greater
      sensitivity was associated with an increase in systolic blood pressure and pulse
      pressure during HSI, most likely due to a shift in the pressure-natriuresis
      curve.

PMID- 11568178
TI  - Gender differences in cardiovascular regulation during recovery from exercise.
AB  - Are women more susceptible to acute postexercise orthostatic hypotension compared
      with men? We hypothesized that decreases in arterial pressure during recovery
      from dynamic exercise are greater in women compared with men. We studied 8 men
      and 11 women during inactive and active recovery from cycling exercise. Heart
      rate, stroke volume (SV), cardiac output, mean arterial pressure (MAP), and total
      peripheral resistance (TPR) were measured during and after 3 min of exercise at
      60% of calculated maximum heart rate. At 1 min after exercise, MAP decreased less
      (P < 0.05) during inactive recovery in men (-18 +/- 2 mmHg) compared with women (
      30 +/- 2 mmHg). This difference was due to greater decreases in SV and less
      increase in TPR during inactive recovery from exercise in women compared with
      men. These differences persisted for 5 min after exercise. MAP decreased less
      during active recovery in men compared with women. These findings suggest that
      women may have increased risk of postexercise orthostatic hypotension and that
      active recovery from exercise may reduce this risk.

PMID- 11568179
TI  - CCAAT/enhancer-binding protein alpha alters histone H3 acetylation at large
      subnuclear domains.
AB  - Transcriptional regulation is commonly associated with local levels of histone
      acetylation, which controls chromatin structure at specific genes or within
      contiguous chromosomal domains. Less well understood are the higher order
      determinants of histone acetylation. The transcription factor, CCAAT/enhancer
      binding protein alpha (C/EBPalpha), concentrates at one higher order structure,
      the peri-centromeric chromatin, and regulates differentiation in many cell types,
      including pituitary cells. We used quantitative fluorescence microscopy to show
      that immunostained acetylated histone H3 is relatively absent from peri
      centromeric domains visible as large structures in mouse pituitary progenitor
      GHFT1-5 cells. GHFT1-5 cells do not contain C/EBPalpha. We observed that
      expression of C/EBPalpha in GHFT1-5 cells leads to an increased level of
      acetylated histone H3, but not acetylated histone H4, at the peri-centromeric
      domains. Only transcriptionally active forms of C/EBPalpha altered histone
      acetylation at the peri-centromeric domain. The altered state of histone
      acetylation at large intranuclear domains may complement, counteract, or
      supersede the more gene-local activities of other transcription factors to
      coordinate C/EBPalpha-induced cellular differentiation.

PMID- 11568180
TI  - A transcriptionally inactive E2F-1 targets the MDM family of proteins for
      proteolytic degradation.
AB  - E2F-1-activated transcription promotes cell cycle progression and apoptosis.
      These functions are regulated by several factors including the E2F-1-binding
      protein MDM2 and the retinoblastoma protein pRb. Using a yeast two-hybrid screen
      we have identified the MDM2-related protein, MDMX, as an E2F-1-binding protein.
      In these studies we find that coexpression of MDMX with E2F-1 results in
      degradation of the MDMX protein. Although this proteolytic degradation can be
      blocked by the protease inhibitors bafilomycin A(1), N-acetyl-Leu-Leu-Norleu-AL,
      and N-acetyl-Leu-Leu-Met-AL, MDMX degradation is not inhibited by lactacystin,
      suggesting that degradation occurs by a proteasome-independent mechanism. Using
      an E2F-1 deletion mutant (E2F-1(180-437)) we show that E2F-1-targeted degradation
      of MDMX does not require the E2F-1 DNA binding domain and therefore is
      independent of E2F-1-driven transcription. We also find that this
      transcriptionally inactive E2F-1 mutant is capable of degrading the MDMX-related
      protein MDM2 and the MDMX isoform MDMX-S. Mapping of the E2F-1 C terminus reveals
      that neither a previously characterized C-terminal MDM2 binding domain nor the
      pRb binding domain on E2F-1 is required for MDMX and MDM2 degradation.

PMID- 11568181
TI  - Structure of crystalline D-Tyr-tRNA(Tyr) deacylase. A representative of a new
      class of tRNA-dependent hydrolases.
AB  - Cell growth inhibition by several d-amino acids can be explained by an in vivo
      production of d-aminoacyl-tRNA molecules. Escherichia coli and yeast cells
      express an enzyme, d-Tyr-tRNA(Tyr) deacylase, capable of recycling such d
      aminoacyl-tRNA molecules into free tRNA and d-amino acid. Accordingly, upon
      inactivation of the genes of the above deacylases, the toxicity of d-amino acids
      increases. Orthologs of the deacylase are found in many cells. In this study, the
      crystallographic structure of dimeric E. coli d-Tyr-tRNA(Tyr) deacylase at 1.55 A
      resolution is reported. The structure corresponds to a beta-barrel closed on one
      side by a beta-sheet lid. This barrel results from the assembly of the two
      subunits. Analysis of the structure in relation with sequence homologies in the
      orthologous family suggests the location of the active sites at the carboxy end
      of the beta-strands. The solved structure markedly differs from those of all
      other documented tRNA-dependent hydrolases.

PMID- 11568182
TI  - Interaction of EVI1 with cAMP-responsive element-binding protein-binding protein
      (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of
      EVI1 and in co-localization in nuclear speckles.
AB  - EVI1 is a very complex protein with two domains of zinc fingers and is
      inappropriately expressed in many types of human myeloid leukemias. Using
      reporter gene assays, several investigators showed that EVI1 is a transcription
      repressor, and recently it was shown that EVI1 interacts with the co-repressor
      carboxyl-terminal binding protein 1 (CtBP1). Earlier, we showed that the
      inappropriate expression of EVI1 in murine hematopoietic precursor cells leads to
      their abnormal differentiation and to increased proliferation. Using biochemical
      assays, we have identified two groups of transcription co-regulators that
      associate with EVI1 presumably to regulate gene expression. One group of co
      regulators includes the CtBP1 and histone deacetylase. The second group includes
      the two co-activators cAMP-responsive element-binding protein-binding protein
      (CBP) and p300/CBP-associated factor (P/CAF), both of which have histone
      acetyltransferase (HAT) activity. All of these proteins require separate regions
      of EVI1 for efficient interaction, and they divergently affect the ability of
      EVI1 to regulate gene transcription in reporter gene assays. Confocal microscopy
      analysis shows that in the majority of the cells, EVI1 is nuclear and diffused,
      whereas in about 10% of the cells EVI1 localizes in nuclear speckles. However, in
      the presence of the added exogenous co-repressors histone deacetylase or CtBP1,
      all of the nuclei have a diffuse EVI1 staining, and the proteins do not appear to
      reside together in obvious nuclear structures. In contrast, when CBP or P/CAF are
      added, defined speckled bodies appear in the nucleus. Analysis of the staining
      pattern indicates that EVI1 and CBP or EVI1 and P/CAF are contained within these
      structures. These nuclear structures are not observed when CBP is substituted
      with a point mutant HAT-inactive CBP with which EVI1 also physically interacts.
      Finally, we show that the interaction of EVI1 with either CBP or P/CAF leads to
      acetylation of EVI1. These results suggest that the assembly of EVI1 in nuclear
      speckles requires the intact HAT activity of the co-activators.

PMID- 11568183
TI  - Structural organization of the fibrinogen-binding region of the clumping factor B
      MSCRAMM of Staphylococcus aureus.
AB  - The clumping factor B (ClfB) of Staphylococcus aureus is a surface protein that
      binds to fibrinogen (Ni Eidhin, D., Perkins, S., Francois, P., Vaudaux, P., Hook,
      M., and Foster, T. J., 1998 Mol. Microbiol. 30, 245-257). The ligand-binding
      activity is located in the approximately 500-residue A-region (residues 44-542),
      which represents the N-terminal half of the MSCRAMM protein. We now hypothesize
      that the ClfB A-region is composed of three subdomains, which we have named N1,
      N2, and N3, respectively. To examine this hypothesis, we expressed recombinant
      forms of the individual putative subdomains, the tandem motifs N12 and N23, and
      the full-length A-region N123. Far UV circular dichroism spectra showed that each
      subdomain is composed mainly of beta-sheets with little or no discernible alpha
      helices. Heat-induced unfolding of individual subdomains occurred with a single
      state transition and was reversible, indicating that the subdomains can fold as
      discreet units. Gel permeation chromatography indicated that N2, N3, and N23 are
      globular. In contrast, domain N1 appeared to be elongated and conferred a
      somewhat elongated structure on segments containing this subdomain (i.e. N12 or
      N123). N123, N12, and N23 all bound to fibrinogen, but N23 had a higher affinity
      for fibrinogen than that observed for the full-length A-region; N123 or for N12.
      However, an extended N terminus of N23 was required for ligand binding. A form of
      N23 that was generated by proteolytic processing and lacked the N-terminal
      extension was unable to bind fibrinogen. Recombinant forms of individual
      subdomains did not bind fibrinogen. The addition of recombinant N23 effectively
      inhibited ClfB-mediated bacterial adherence to fibrinogen, and N123 caused some
      reduction in bacterial attachment, whereas N12 was essentially inactive.
      Antibodies raised against the central N2 domain of the A-region were the most
      effective at inhibiting bacterial adhesion to immobilized fibrinogen, although
      anti-N3 or anti-N1 antibodies also caused some reduction in ClfB-mediated
      adherence to fibrinogen.

PMID- 11568184
TI  - Biochemical activities associated with mouse Mcm2 protein.
AB  - Mcm2, a member of the Mcm2-7 protein family essential for the initiation of DNA
      replication, has several biochemical activities including the ability to inhibit
      the Mcm4,6,7 helicase. In this study, we characterized the activities associated
      with Mcm2 and determined the region required for them. It was found that Mcm2
      deleted at an amino-terminal portion is able to bind to an Mcm4,6,7 hexameric
      complex and to inhibit its DNA helicase activity. The same deletion mutant of
      Mcm2 and the carboxyl-terminal half of Mcm2 were both able to bind to Mcm4,
      suggesting that the carboxyl-half of Mcm2 binds to Mcm4 to disassemble the
      Mcm4,6,7 hexamer. Phosphorylation of Mcm2,4,6,7 complexes with Cdc7 kinase showed
      that the amino-terminal region of Mcm2 is required for the phosphorylation, and
      it contains major Cdc7-mediated phosphorylation sites. We also found that Mcm2
      itself can assemble a nucleosome-like structure in vitro in the presence of H3/H4
      histones. The amino-terminal region of Mcm2 was required for the activity where a
      histone-binding domain is located. Finally, we identified a region required for
      the nuclear localization of Mcm2. The function of Mcm2 is discussed based on
      these biochemical characteristics.

PMID- 11568185
TI  - Developmental regulation of a novel outwardly rectifying mechanosensitive anion
      channel in Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans offers unique experimental advantages for
      defining the molecular basis of anion channel function and regulation. However,
      the relative inaccessibility of somatic cells in adult animals greatly limits
      direct electrophysiological studies of channel activity. We developed methods to
      routinely isolate and patch clamp C. elegans embryo cells and oocytes and to
      culture and patch clamp neurons and muscle cells. Dissociated embryonic cells
      express a robust outwardly rectifying anion current that is activated by membrane
      stretch and depolarization. This current, termed I(Cl,mec), is inhibited by anion
      and mechanosensitive channel inhibitors. I(Cl,mec) has broad anion selectivity
      and the channel has a unitary conductance of 5-7 picosiemens. I(Cl,mec) is not
      detectable in whole-cell or isolated patch recordings from oocytes, cultured
      muscle cells, and cultured neurons but is expressed in single cell and later
      embryos. Channel density is high, and the current is observed in >80% of membrane
      patches. Macroscopic currents of 40-120 pA at +100 mV are typically observed in
      inside-out membrane patches formed using low resistance patch pipettes. Isolated
      membrane patches of early embryonic cells therefore contain 60-200 I(Cl,mec)
      channels. The apparent activation of I(Cl,mec) shortly after fertilization and
      its down-regulation in terminally differentiated cells suggests that the channel
      may play important roles in embryogenesis and/or cytokinesis.

PMID- 11568186
TI  - Spectroscopic and functional properties of novel 2[4Fe-4S] cluster-containing
      ferredoxins from the green sulfur bacterium Chlorobium tepidum.
AB  - Two distinct ferredoxins, Fd I and Fd II, were isolated and purified to
      homogeneity from photoautotrophically grown Chlorobium tepidum, a moderately
      thermophilic green sulfur bacterium that assimilates carbon dioxide by the
      reductive tricarboxylic acid cycle. Both ferredoxins serve a crucial role as
      electron donors for reductive carboxylation, catalyzed by a key enzyme of this
      pathway, pyruvate synthase/pyruvate ferredoxin oxidoreductase. The reduction
      potentials of Fd I and Fd II were determined by cyclic voltammetry to be -514 and
      -584 mV, respectively, which are more electronegative than any previously studied
      Fds in which two [4Fe-4S] clusters display a single transition. Further
      spectroscopic studies indicated that the CD spectrum of oxidized Fd I closely
      resembled that of Fd II; however, both spectra appeared to be unique relative to
      ferredoxins studied previously. Double integration of the EPR signal of the two
      Fds yielded approximately approximately 2.0 spins per molecule, compatible with
      the idea that C. tepidum Fd I and Fd II accept 2 electrons upon reduction. These
      results suggest that the C. tepidum Fd I and Fd II polypeptides each contain two
      bound [4Fe-4S] clusters. C. tepidum Fd I and Fd II are novel 2[4Fe-4S] Fds, which
      were shown previously to function as biological electron donors or acceptors for
      C. tepidum pyruvate synthase/pyruvate ferredoxin oxidoreductase (Yoon, K.-S.,
      Hille, R., Hemann, C. F., and Tabita, F. R. (1999) J. Biol. Chem. 274, 29772
      29778). Kinetic measurements indicated that Fd I had approximately 2.3-fold
      higher affinity than Fd II. The results of amino acid sequence alignments,
      molecular modeling, oxidation-reduction potentials, and spectral properties
      strongly indicate that the C. tepidum Fds are chimeras of both clostridial-type
      and chromatium-type Fds, suggesting that the two Fds are likely intermediates in
      the evolutional development of 2[4Fe-4S] clusters compared with the well
      described clostridial and chromatium types.

PMID- 11568187
TI  - Kinetic studies of the TATA-binding protein interaction with cisplatin-modified
      DNA.
AB  - The TATA-binding protein (TBP) recognizes the TATA box element of transcriptional
      promoters and recruits other initiation factors. This essential protein binds
      selectively to cisplatin-damaged DNA. Electrophoretic mobility shift assays were
      performed to study the kinetics of TBP binding both to the TATA box and to
      cisplatin-damaged DNA in different sequence contexts. TBP binds with high
      affinity (K(d) = 0.3 nm) to DNA containing site-specific cisplatin 1,2
      intrastrand d(GpG) cross-links. The k(on) and k(off) values for the formation of
      these TBP complexes are 1-3 x 10(5) m(-1) s(-1) and approximately 1-5 x 10(-4) s(
      1), respectively, similar to the corresponding values for the formation of a TBP
      TATA box complex. In electrophoretic mobility shift assay competition assays,
      cisplatin-damaged DNA extensively sequesters TBP from its natural binding site,
      the TATA box. Nine DNA probes were prepared to determine the flanking sequence
      dependence of TBP binding to cisplatin-modified DNA. TBP clearly displays
      sequence context selectivity for platinated DNA, very similar to but not as
      dramatic as that of the high mobility group protein HMGB1. When TBP was added to
      an in vitro nucleotide excision repair assay, it specifically shielded cisplatin
      modified 1,2-(GpG) intrastrand cross-links from repair. These results indicate
      that TBP is likely to be a key protein in mediating the cytotoxicity of
      cisplatin.

PMID- 11568188
TI  - Structure of DNA polymerase delta from Saccharomyces cerevisiae.
AB  - DNA polymerase delta (Pol delta) from Saccharomyces cerevisiae consists of three
      subunits, Pol3 (125 kDa), Pol31 (55 kDa), and Pol32 (40 kDa), present at a 1:1:1
      stoichiometry in purified preparations. Previously, based on gel filtration
      studies of Pol delta, we suggested that the enzyme may be a dimer of catalytic
      cores, with dimerization mediated by the Pol32 subunit (Burgers, P. M., and
      Gerik, K. J. (1998) J. Biol. Chem. 273, 19756-19762). We now report on extensive
      gel filtration, glycerol gradient sedimentation, and analytical equilibrium
      centrifugation studies of Pol delta and of several subassemblies of Pol delta.
      The hydrodynamic parameters of these assemblies indicate that (i) Pol32 is a rod
      shaped protein with a frictional ratio f/f(0) = 2.22; (ii) any complex containing
      Pol32 also has an extremely asymmetric shape; (iii) the results of these studies
      are independent of concentration (varied between 0.1-20 microm); (iv) all
      complexes are monomeric under the conditions studied (up to 20 microm). Moreover,
      a two-hybrid analysis of the Pol32 subunit did not detect a Pol32-Pol32
      interaction in vivo. Therefore, we conclude that the assembly structure of Pol
      delta is that of a monomer.

PMID- 11568189
TI  - Long-term results of treatment of fractures of the medial humeral epicondyle in
      children.
AB  - BACKGROUND: The treatment of isolated, displaced fractures of the medial humeral
      epicondyle in children is controversial. Both plaster cast immobilization without
      reduction and open reduction and internal fixation have been advocated. The
      purpose of this long-term retrospective study was to analyze the functional and
      radiographic results of both nonsurgical and surgical management of these
      injuries. METHODS: Forty-two patients who had had an isolated fracture of the
      medial humeral epicondyle with displacement of >5 mm at an average age of twelve
      years (range, eight to fifteen years) were evaluated at an average age of forty
      five years (range, thirty to sixty-one years). The patients were divided into
      three groups that were comparable with regard to the amount of fracture
      displacement, age at the time of the fracture, age at the time of follow-up,
      sports activities and occupation, and duration of follow-up. In Group I (nineteen
      patients), the fracture had been treated with a long-arm plaster cast without
      reduction of the displaced medial epicondyle. In Group II (seventeen patients),
      open reduction and internal fixation with either Kirschner wires or a T-nail had
      been performed. In Group III (six patients), the epicondylar fragment had been
      excised with suture reattachment of the tendons and the medial collateral
      ligament. RESULTS: According to a functional grading scale, there were sixteen
      good and three fair results in Group I. All but two patients were seen to have
      nonunion of the fragment on follow-up radiographs, but all had a normal result on
      valgus stress-testing of the elbow. The range of motion of the elbow was either
      normal or minimally decreased, and the grip strength of the ipsilateral hand was
      normal. There were fifteen good and two fair results in Group II. All patients
      had union of the medial epicondyle, with various radiographic deformities of the
      medial epicondyle, but the functional results were similar to those of the Group
      I patients. The Group-III patients had four poor and two fair results. Four had
      constant pain at the elbow and paresthesias in the distribution of the ulnar
      nerve. One patient had a restricted range of motion of the elbow, four patients
      had an unstable elbow, and three patients had decreased grip strength of the
      ipsilateral hand. CONCLUSIONS: In our study, nonsurgical treatment of isolated
      fractures of the medial humeral epicondyle with between 5 and 15 mm of
      displacement yielded good long-term results similar to those obtained with open
      reduction and internal fixation. The nonunion of the epicondylar fragment that
      was present in most patients who had been treated only with a cast did not
      adversely affect the functional results. Surgical excision of the medial
      epicondylar fragment should be avoided because the long-term results are poor.

PMID- 11568190
TI  - The value of magnetic resonance imaging of the lumbar spine to predict low-back
      pain in asymptomatic subjects : a seven-year follow-up study.
AB  - BACKGROUND: In 1989, a group of sixty-seven asymptomatic individuals with no
      history of back pain underwent magnetic resonance imaging of the lumbar spine.
      Twenty-one subjects (31%) had an identifiable abnormality of a disc or of the
      spinal canal. In the current study, we investigated whether the findings on the
      scans of the lumbar spine that had been made in 1989 predicted the development of
      low-back pain in these asymptomatic subjects. METHODS: A questionnaire concerning
      the development and duration of low-back pain over a seven-year period was sent
      to the sixty-seven asymptomatic individuals from the 1989 study. A total of fifty
      subjects completed and returned the questionnaire. A repeat magnetic resonance
      scan was made for thirty-one of these subjects. Two neuroradiologists and one
      orthopaedic spine surgeon interpreted the original and repeat scans in a blinded
      fashion, independent of clinical information. At each disc level, any
      radiographic abnormality, including bulging or degeneration of the disc, was
      identified. Radiographic progression was defined as increasing severity of an
      abnormality at a specific disc level or the involvement of additional levels.
      RESULTS: Of the fifty subjects who returned the questionnaire, twenty-nine (58%)
      had no back pain. Low-back pain developed in twenty-one subjects during the seven
      year study period. The 1989 scans of these subjects demonstrated normal findings
      in twelve, a herniated disc in five, stenosis in three, and moderate disc
      degeneration in one. Eight individuals had radiating leg pain; four of them had
      had normal findings on the original scans, two had had spinal stenosis, one had
      had a disc protrusion, and one had had a disc extrusion. In general, repeat
      magnetic resonance imaging scans revealed a greater frequency of disc herniation,
      bulging, degeneration, and spinal stenosis than did the original scans.
      CONCLUSIONS: The findings on magnetic resonance scans were not predictive of the
      development or duration of low-back pain. Individuals with the longest duration
      of low-back pain did not have the greatest degree of anatomical abnormality on
      the original, 1989 scans. Clinical correlation is essential to determine the
      importance of abnormalities on magnetic resonance images.

PMID- 11568191
TI  - Total knee arthroplasty in patients with ankylosing spondylitis.
AB  - BACKGROUND: Ankylosing spondylitis is a seronegative spondyloarthropathy that
      primarily affects the sacroiliac joints, spine, hips, and, less commonly, the
      knee joints. The purpose of this study was to evaluate the results in a
      consecutive group of patients with ankylosing spondylitis who underwent total
      knee arthroplasty. METHODS: The results of thirty total knee arthroplasties in
      twenty patients with ankylosing spondylitis were reviewed. There were seventeen
      men and three women, with an average age of fifty-five years (range, twenty-eight
      to sixty-seven years) at the time of the arthroplasty. The diagnosis of
      ankylosing spondylitis was established preoperatively with use of the New York
      criteria. All patients received a cemented condylar-type implant. The average
      duration of follow-up was 11.2 years (range, three to sixteen years). RESULTS:
      The average Knee Society pain score improved from 14 points preoperatively to
      76.3 points at the time of the latest follow-up. The improvement in the average
      Knee Society function score was less impressive, with an increase from 16.3
      points preoperatively to 58.7 points at the time of the latest follow-up. The
      average arc of motion was 84.8 degrees prior to the arthroplasty and 86.7 degrees
      at the time of the final follow-up. Six knees (20%) had heterotopic bone
      formation. Three knees required manipulation under anesthesia because of poor
      motion postoperatively. There was one revision, due to loosening of a patellar
      component. All other components were radiographically stable at the time of the
      latest follow-up. CONCLUSIONS: Total knee arthroplasty with cement in patients
      with ankylosing spondylitis provided excellent pain relief and durable fixation
      at an average of 11.2 years postoperatively. However, patients with ankylosing
      spondylitis are at increased risk for the development of stiffness and
      heterotopic bone formation.

PMID- 11568192
TI  - Educating medical students about musculoskeletal problems. Are community needs
      reflected in the curricula of Canadian medical schools?
AB  - BACKGROUND: Musculoskeletal problems are a common reason why patients present for
      medical treatment. The purpose of the present study was to review the curricula
      of Canadian medical schools to determine whether they prepare their students for
      the demands of practice with respect to musculoskeletal problems. METHODS: The
      amount of time spent on musculoskeletal education at each of Canada's medical
      schools was reviewed by surveying the directors (or equivalents) of all sixteen
      undergraduate musculoskeletal programs. With use of data from this survey and the
      Association of American Medical Colleges' guide to curricula, the percentage of
      the total curriculum devoted to musculoskeletal education was determined. The
      prevalence of disorders related to the musculoskeletal system among patients of
      primary care physicians was determined on an international basis by reviewing the
      literature and on a local basis by surveying all primary care physicians
      affiliated with the University of British Columbia's Department of Family
      Medicine. RESULTS: The curriculum analysis revealed that, on the average, medical
      schools in Canada devoted 2.26% (range, 0.61% to 4.81%) of their curriculum time
      to musculoskeletal education. The questionnaires completed by the directors of
      the undergraduate programs indicated widespread dissatisfaction with the
      musculoskeletal education process and, specifically, with the amount of time
      devoted to musculoskeletal education. Our literature review and survey of local
      family physicians revealed that between 13.7% and 27.8% of North American
      patients presenting to a primary care physician have a chief symptom that is
      directly related to the musculoskeletal system. CONCLUSION: There is a marked
      discrepancy between the musculoskeletal knowledge and skill requirements of a
      primary care physician and the time devoted to musculoskeletal education in
      Canadian medical schools.

PMID- 11568193
TI  - Operative treatment of interdigital neuroma. A long-term follow-up study.
AB  - BACKGROUND: The literature regarding the outcome of surgical treatment of
      interdigital neuroma is incomplete. The purpose of this study was to assess the
      demographics associated with the presentation of an interdigital neuroma as well
      as the long-term clinical results of operative resection by a single surgeon.
      METHODS: A retrospective review of the patient records of one orthopaedic foot
      and ankle surgeon identified eighty-two patients who had been treated operatively
      for a primary, persistently painful interdigital neuroma more than three years
      previously. Of these eighty-two patients, sixty-six (seventy-one feet, seventy
      four neuromas) returned at an average of 5.8 years for a follow-up evaluation,
      which included a review of the interval history since the surgery, a physical
      examination, a radiographic evaluation, and an assessment of the patient's
      satisfaction with the result of the surgery. RESULTS: Overall satisfaction was
      rated as excellent or good by fifty-six (85%) of the sixty-six patients. Forty
      six (65%) of the seventy-one feet were pain-free at the time of final follow-up.
      The patients who had had either bilateral neuroma excision or excisions of
      adjacent neuromas in the same foot in a staged fashion had a slightly lower level
      of satisfaction, but this difference was not significant. While major activity
      restrictions following surgery were uncommon, mild or major shoe-wear
      restrictions were noted by forty-six of the sixty-six patients. Although there
      was subjective numbness in thirty-six of the seventy-one feet, the pattern of
      numbness was quite variable and it was bothersome in only four feet. CONCLUSION:
      With careful preoperative evaluation and patient selection, resection of a
      symptomatic interdigital neuroma through a dorsal approach can result in a high
      percentage of successful results more than five years following the procedure.

PMID- 11568194
TI  - Arthroscopically assisted reconstruction of the anterior cruciate ligament. A
      follow-up report.
AB  - BACKGROUND: The purpose of this study was to further delineate the outcome of
      arthroscopically assisted anterior cruciate ligament reconstruction in 125
      patients who had previously been followed for two to five years. One of the
      original 125 patients was excluded from the present study because of insufficient
      follow-up, and an additional group of 101 patients was added. All 225 patients in
      the present study were followed for a minimum of six years. METHODS: Patients
      were randomly assigned to reconstruction with a double-stranded semitendinosus
      gracilis graft with use of a two-incision technique (group I), reconstruction
      with a patellar ligament graft with use of a two-incision technique (group II),
      or reconstruction with a patellar ligament graft with use of a single-incision
      endoscopic technique (group III). The groups were compared with regard to the
      rate of graft failure, the amount of instability, knee strength, radiographic
      signs of degenerative changes, and functional outcome. RESULTS: There was no
      significant difference among the three groups with regard to the rate of graft
      failure, the amount of knee instability, or the functional outcome. A normal or
      nearly normal functional outcome was recorded for 208 (92%) of the 225 patients.
      There were significant differences among the groups with regard to quadriceps
      muscle-strength deficits: group I had fewer patients with deficits than group
      III, and groups I and III both had fewer patients with deficits than group II (p
      = 0.04). There also were significant differences among the groups with regard to
      hamstring muscle-strength deficits: group III had fewer patients with deficits
      than group II, and group II had fewer patients with deficits than group I (p <
      0.01). Twelve knees (16%) in group I, six knees (8%) in group II, and eight knees
      (11%) in group III showed radiographic evidence of progressive degenerative
      changes, but the differences among the three groups were not significant.
      CONCLUSION: Although 11.6% of the 225 knees had radiographic evidence of
      degenerative arthritis at a minimum of six years after arthroscopically assisted
      reconstruction of the anterior cruciate ligament, the choice of graft and the
      technique of reconstruction did not seem to affect the rate of development of
      these changes.

PMID- 11568195
TI  - The porous coated anatomic total hip replacement. A ten to fourteen-year follow
      up study of a cementless total hip arthroplasty.
AB  - BACKGROUND: We previously reported our two and five-year results of arthroplasty
      with the Porous Coated Anatomic total hip prosthesis. We now report on the
      performance of this prosthesis at ten to fourteen years. METHODS: The results of
      311 total hip replacements in which a Porous Coated Anatomic prosthesis was
      inserted without cement in 279 patients were analyzed prospectively. The average
      age of the patients at the time of the replacement was sixty--one years (range,
      twenty to eighty-one years). Sixty-four patients (seventy-six hips) died
      postoperatively. Forty-five patients (forty-seven hips) were lost to follow-up,
      and four were excluded because of their medical condition. One hundred and sixty
      eight patients (187 hips) were followed for ten to fourteen years (average,
      twelve years). Seventeen of those patients (seventeen hips) had a revision.
      RESULTS: The overall survival rate (with any revision as the end point) was 90.0%
      +/- 5.4% at fourteen years, with an average Harris hip score of 85 +/- 14 points.
      The prevalence of thigh pain was 36% (fifty-six of 157) in the late period (more
      than ten years postoperatively). Radiographs showed stable fixation, with bone
      ingrowth, of 83% (130) of the 156 acetabular components and 88% (137) of the 156
      femoral components at the latest follow-up evaluation. Men had a significantly
      higher rate of femoral osteolysis than did women (p < 0.001). The rates of
      acetabular and femoral osteolysis associated with 32-mm femoral heads (49%
      [twenty-three] of forty-seven and 70% [thirty-three] of forty-seven,
      respectively) were significantly higher (p < 0.01) than those associated with 26
      mm heads (26% [twenty-eight] of 109 and 30% [thirty-three] of 109, respectively).
      Despite this, revision (removal or exchange of components) was not directly
      related to head size; instead, it was related to polyethylene thickness.
      CONCLUSIONS: There have been persistent problems with the Porous Coated Anatomic
      hip system, including thigh pain and an increasing prevalence of osteolysis with
      time. Revision because of aseptic loosening was related more to the thickness of
      the polyethylene liner than to the size of the femoral head. Femoral heads with a
      32-mm diameter did not increase the risk for revision provided that an adequate
      thickness of polyethylene had been used.

PMID- 11568196
TI  - The effects of tibial rotation on posterior translation in knees in which the
      posterior cruciate ligament has been cut.
AB  - BACKGROUND: One of the most useful clinical tests for diagnosing an isolated
      injury of the posterior cruciate ligament is the posterior drawer maneuver
      performed with the knee in 90 degrees of flexion. Previously, it was thought that
      internally rotating the tibia during posterior drawer testing would decrease
      posterior laxity in a knee with an isolated posterior cruciate ligament injury.
      In this study, we evaluated the effects of internal and external tibial rotation
      on posterior laxity with the knee held in varying degrees of flexion after the
      posterior cruciate and meniscofemoral ligaments had been cut. MATERIALS AND
      METHODS: Twenty cadaveric knees were used. Each knee was mounted in a fixture
      with six degrees of freedom, and anterior and posterior forces of 150 N were
      applied. The testing was conducted with the knee in 90 degrees, 60 degrees, 30
      degrees, and 0 degrees of flexion with the tibia in neutral, internal, and
      external rotation. All knees were tested with the posterior cruciate and
      meniscofemoral ligaments intact and transected. Repeated-measures analysis of
      variance was used for statistical analysis. RESULTS: At 30 degrees, 60 degrees,
      and 90 degrees of flexion, there was a significant increase in posterior laxity
      following transection of the posterior cruciate and meniscofemoral ligaments. At
      60 degrees and 90 degrees of flexion, there was significantly less posterior
      laxity when the tibia was held in internal compared with external rotation. At 0
      degrees and 30 degrees of flexion, there was no significant difference in
      posterior laxity when the tibia was held in internal compared with external
      rotation. CONCLUSIONS: After the posterior cruciate and meniscofemoral ligaments
      had been cut, posterior laxity was significantly decreased by both internal and
      external rotation of the tibia. Internal tibial rotation resulted in
      significantly less laxity than external tibial rotation did at 60 degrees and 90
      degrees of knee flexion.

PMID- 11568197
TI  - Effect of capsular injury on acromioclavicular joint mechanics.
AB  - BACKGROUND: Traumatic disruption of the acromioclavicular joint capsule is
      associated with pain and instability after the injury and may lead to
      degenerative joint disease. The objective of this study was to quantify the
      effect of transection of the acromioclavicular joint capsule on the kinematics
      and the in situ forces in the coracoclavicular ligaments in response to external
      loading conditions. METHODS: Eleven fresh-frozen human cadaveric shoulders were
      tested with use of a robotic/universal force-moment sensor testing system. The
      shoulders were subjected to three loading conditions (an anterior, posterior, and
      superior load of 70 N) in their intact state and after transection of the
      acromioclavicular joint capsule. RESULTS: Transection of the capsule resulted in
      a significant (p < 0.05) increase in anterior translation (6.4 mm) and posterior
      translation (3.6 mm) but not in superior translation (1.6 mm). The effect of
      capsule transection on the forces in the coracoclavicular ligaments was also
      significant (p < 0.05) in response to anterior and posterior loading but not in
      response to superior loading. However, differences were found between the forces
      in the trapezoid and conoid ligaments. Under an anterior load, the mean in situ
      force (and standard deviation) in the trapezoid increased from 14 +/- 14 N to 25
      +/- 19 N, while the mean force in the conoid increased from 15 +/- 14 N to 49 +/-
      23 N, or 227%. In contrast, in response to a posterior load, the mean in situ
      force in the trapezoid increased from 23 +/- 15 N to 38 +/- 23 N, or 66% (p <
      0.05), while the mean force in the conoid increased only 9%. CONCLUSIONS AND
      CLINICAL RELEVANCE: The large differences in the change of force in the conoid
      and trapezoid ligaments suggest that these ligaments should not be considered as
      one structure when surgical treatment is considered. Furthermore, transection of
      the capsule resulted in a shift of load to the coracoclavicular ligaments, which
      may render the intact coracoclavicular ligaments more likely to fail with
      anterior or posterior loading. The results of the present study also suggest that
      the intact coracoclavicular ligaments cannot compensate for the loss of capsular
      function during anterior-posterior loading as occurs in type-II acromioclavicular
      joint injuries.

PMID- 11568198
TI  - Extra-large uncemented hemispherical acetabular components for revision total hip
      arthroplasty.
AB  - BACKGROUND: Extra-large uncemented components provide several advantages for
      acetabular revision, but limited information is available on the results of their
      use. The purpose of this study was to evaluate, at a minimum of five years, the
      results associated with the use of an extra-large uncemented porous-coated
      component for acetabular revision in the presence of bone loss. METHODS: Eighty
      nine extra-large uncemented hemispherical acetabular components were used for
      revision after aseptic failure of a total hip arthroplasty in forty-six men and
      forty-three women (mean age at revision, fifty-nine years; range, thirty to
      eighty-three years). The revision implant (a Harris-Galante-I or II cup fixed
      with screws) had an outside diameter of > or = 66 mm in men and > or = 62 mm in
      women. Seventy-nine patients had a segmental or combined segmental and cavitary
      acetabular bone deficiency before the revision. Particulate bone graft was used
      in fifty-four hips and bulk bone graft, in nine. RESULTS: One patient died with
      the acetabular component intact and two patients were lost to follow-up within
      five years after the operation. At the time of the last follow--up, four
      acetabular components had been removed or revised again (two for aseptic
      loosening). All of the remaining patients were followed clinically for at least
      five years (mean, 7.2 years; range, 5.0 to 11.3 years). In the hips that were not
      revised again, only two sockets had definite radiographic evidence of loosening.
      All four of the sockets that loosened were in hips that had had combined cavitary
      and segmental bone loss preoperatively. In the hips that were not revised again,
      the mean modified Harris hip score increased from 56 points preoperatively to 83
      points at the time of the most recent follow-up. The most frequent complication,
      dislocation of the hip, occurred in eleven patients. The probability of survival
      of the acetabular component at eight years was 93% (95% confidence interval, 85%
      to 100%) with removal for any reason as the end point, 98% (95% confidence
      interval, 92% to 100%) with revision for aseptic loosening as the end point, and
      95% (95% confidence interval, 88% to 100%) with radiographic evidence of
      loosening or revision for aseptic loosening as the end point. CONCLUSIONS: This
      study demonstrates that extra-large uncemented components used for acetabular
      revision in the presence of bone loss perform very well and have a low rate of
      aseptic loosening at the time of intermediate-term follow-up.

PMID- 11568199
TI  - Tardy posterolateral rotatory instability of the elbow due to cubitus varus.
AB  - BACKGROUND: Cubitus varus has long been considered merely a cosmetic deformity.
      The purpose of this paper is to demonstrate a causal relationship between cubitus
      varus and instability of the elbow. METHODS: In twenty-four patients (twenty-five
      limbs) with a cubitus varus deformity following a pediatric distal humeral
      fracture or resulting from a congenital anomaly (three limbs of two patients),
      tardy posterolateral rotatory instability of the elbow developed approximately
      two to three decades after the deformity occurred. All patients presented with
      lateral elbow pain and recurrent instability. The average varus deformity was 15
      degrees (range, 0 degrees to 35 degrees ). Surgery was performed in twenty-one
      patients (twenty-two limbs). Treatment consisted of reconstruction of the lateral
      collateral ligament and osteotomy in seven limbs, ligament reconstruction alone
      in ten, osteotomy alone in four, and total elbow arthroplasty in one. RESULTS: In
      three patients, the triceps muscle was dynamically stimulated intraoperatively to
      contract while resisting extension of the elbow. This produced posterolateral
      rotatory subluxation of the elbow, which was reversed by corrective osteotomy and
      lateral transposition of a portion of the medial head of the triceps that
      originally had been attached to the elongated, deformed medial aspect of the
      olecranon. At an average of three years (minimum, one year) after the operation,
      the result was good or excellent for nineteen of the twenty-two limbs that had
      undergone an operation; three limbs had persistent instability. CONCLUSIONS: With
      cubitus varus, the mechanical axis, the olecranon, and the triceps line of pull
      are all displaced medially. The repetitive external rotation torque on the ulna
      permitted by these deformities can stretch the lateral collateral ligament
      complex and lead to posterolateral rotatory instability. Thus, cubitus varus
      deformity secondary to supracondylar malunion or congenital deformity of the
      distal part of the humerus may not always be a benign condition and may have
      important long-term clinical implications. Operative correction can relieve
      symptoms of instability. The indications for preventive corrective osteotomy
      remain to be determined.

PMID- 11568200
TI  - Accuracy of detecting screw penetration of the acetabulum with intraoperative
      fluoroscopy and computed tomography.
AB  - BACKGROUND: The purpose of this study was to determine the accuracy of computed
      tomography and fluoroscopy in assessing joint penetration by periacetabular
      screws. METHODS: A 3.5-mm acetabular periarticular screw was inserted in each of
      thirty-nine cadaveric hemipelves. Twenty screws were intentionally directed to
      violate the articular surface, whereas nineteen screws were positioned to avoid
      the articular surface. Using two fluoroscopic views (tangential and axial) in a
      manner simulating the clinical setting, an examiner blinded to the actual screw
      location determined whether each screw was violating the articular surface. In
      addition, each hemipelvis was examined with computed tomography with use of two
      different techniques: (1) a 1-mm slice thickness at 1-mm intervals, and (2) a 4
      mm slice thickness at 3-mm intervals. Each scan was evaluated by another examiner
      who was blinded to the actual screw location. Sensitivity, specificity, and
      percent correct interpretations were then calculated for each method. RESULTS:
      The sensitivity, specificity, and percent correct interpretations were 95%, 84%,
      and 90%, respectively, for axial fluoroscopy; 85%, 89%, and 87% for tangential
      fluoroscopy; 100%, 84%, and 92% for the computed tomography scans with a 1-mm
      slice thickness at 1-mm intervals; and 100%, 58%, and 79% for the computed
      tomography scans with a 4-mm slice thickness at 3-mm intervals. Tangential
      fluoroscopy was found to be more specific than the computed tomography scans with
      a 4-mm slice thickness at 3-mm intervals (p = 0.02). No other significant
      differences were found. CONCLUSIONS: Fluoroscopy and computed tomography are
      equally accurate for determining intra-articular screw penetration. Computed
      tomography scans with thick slices (4 mm at 3-mm intervals) have a low
      specificity. Their use postoperatively may lead to a false-positive
      interpretation of the scan and unnecessary exploration of a hip for screw
      penetration.

PMID- 11568202
TI  - Atraumatic bilateral patellar tendon rupture, A case report and review of the
      literature.

PMID- 11568201
TI  - Patellar resurfacing in total knee arthroplasty. A prospective, randomized,
      double-blind study with five to seven years of follow-up.
AB  - BACKGROUND: Whether to resurface the patella during a primary total knee
      arthroplasty performed for the treatment of degenerative osteoarthritis remains a
      controversial issue. Parameters that have been suggested as being useful in
      guiding this decision include patient height and weight, the presence of anterior
      knee pain preoperatively, and the grade of chondromalacia encountered
      intraoperatively. The purpose of this study was to determine whether these
      parameters were predictive of the clinical result following total knee
      arthroplasty with or without patellar resurfacing. METHODS: Eighty-six patients
      (118 knees) undergoing primary total knee arthroplasty for the treatment of
      osteoarthritis were enrolled in a prospective, randomized, double-blind study.
      All patients received the same posterior-cruciate-sparing total knee prosthetic
      components. Patients were randomized to treatment with or without resurfacing of
      the patella. Evaluations consisted of the determination of a Knee Society
      clinical score, the completion of a patient satisfaction questionnaire, specific
      questions relating to patellofemoral symptoms, and radiographs. Sixty-seven
      patients (ninety-three knees) were followed for a minimum of five years (range,
      sixty to eighty-four months; average, 70.5 months). RESULTS: With the numbers
      available, there was no significant difference between the groups treated with
      and without resurfacing with regard to the overall Knee Society score or the pain
      and function subscores. Obesity, the degree of patellar chondromalacia, and the
      presence of preoperative anterior knee pain did not predict postoperative
      clinical scores or the presence of postoperative anterior knee pain. CONCLUSIONS:
      The occurrence of anterior knee pain could not be predicted with any clinical or
      radiographic parameter studied. On the basis of these results, it seems likely
      that postoperative anterior knee pain is related either to the component design
      or to the details of the surgical technique, such as component rotation, rather
      than to whether or not the patella is resurfaced.

PMID- 11568203
TI  - Peroneus longus tendon obstructing reduction of cuboid dislocation. A report of
      two cases.

PMID- 11568204
TI  - An unusual cause of groin pain following hip replacement. A case report.

PMID- 11568205
TI  - Metastatic mixed tumor arising in bone. A case report and review of the
      literature.

PMID- 11568207
TI  - The education of future orthopaedists--deja vu.

PMID- 11568208
TI  - Pain: friend or foe?

PMID- 11568209
TI  - Osteotomy of the upper portion of the tibia for degenerative arthritis of the
      knee. A preliminary report by Mark B. Conventry, MD. From the Section of
      Orthopedic Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. 1965.

PMID- 11568210
TI  - The education of future orthopaedists: a need for improvement.

PMID- 11568211
TI  - In the best interests of the patient: accepting or overriding a surrogate's
      decision.

PMID- 11568212
TI  - Conflict of interest, bias, and objectivity in research articles.

PMID- 11568213
TI  - Surgical options for middle-aged patients with osteoarthritis of the knee.

PMID- 11568214
TI  - In reference to sources: peer-reviewed vs. non-peer-reviewed articles,
      proceedings, and unpublished data.

PMID- 11568215
TI  - Cultivating a valuable hybrid: the orthopaedic clinician-scientist.

PMID- 11568216
TI  - Systematic reviews, meta-analyses, and methodology.

PMID- 11568217
TI  - Screening for infection to determine treatment in second-stage reimplantation of
      total knee prostheses.

PMID- 11568218
TI  - The posterior fat pad sign and use of comparison radiographs in the diagnosis of
      occult fractures.

PMID- 11568219
TI  - Arthrodesis and the total-contact cast in treatment of the neuropathic foot.

PMID- 11568220
TI  - Historical and current treatment of calcaneal fractures.

PMID- 11568221
TI  - Residents as teachers.

PMID- 11568222
TI  - What's new in adult reconstructive knee surgery.

PMID- 11568224
TI  - Joannes Zacharias Actuarius. A witness of late Byzantine uroscopy, closely linked
      with Thessaloniki.

PMID- 11568225
TI  - Evidence-based medicine vs inferential reasoning: the case of hypertension
      associated with renal disease.

PMID- 11568226
TI  - An integrated approach to end-stage renal disease.

PMID- 11568227
TI  - The polyuric syndromes.

PMID- 11568228
TI  - Renal diseases associated with malignancies.

PMID- 11568229
TI  - The place of calcium and calcimimetics in the treatment of secondary
      hyperparathyroidism.

PMID- 11568230
TI  - Dialysis modalities in patients with acute renal failure.

PMID- 11568231
TI  - Nutrition in patients with acute renal failure.

PMID- 11568232
TI  - Apoptosis in acute renal failure.

PMID- 11568233
TI  - Open questions on Balkan nephropathy.

PMID- 11568234
TI  - The significance of apoptosis for early diagnosis of Balkan nephropathy.

PMID- 11568235
TI  - Apoptosis and p53 status of the upper urothelial carcinomas from Balkan endemic
      nephropathy regions.

PMID- 11568236
TI  - Hyponatraemia--review of a controversial case.

PMID- 11568237
TI  - Sodium and the kidney: the non-modulator concept.

PMID- 11568238
TI  - Specific organ protection by blocking the renin-angiotensin system.

PMID- 11568239
TI  - Lessons from the recent trials on hypertension treatment.

PMID- 11568240
TI  - Treatment of hypertension in patients with chronic renal failure.

PMID- 11568241
TI  - Autoimmunity and autoimmune disease.

PMID- 11568242
TI  - Goodpasture's disease.

PMID- 11568243
TI  - Lupus nephritis.

PMID- 11568244
TI  - Mechanisms of renal damage in mixed cryoglobulinaemia nephritis.

PMID- 11568245
TI  - Renal involvement in antiphospholipid syndrome.

PMID- 11568246
TI  - Kidney injury in Sjogren's syndrome.

PMID- 11568247
TI  - Genetics of systemic autoimmunity and glomerulonephritis in mouse models of
      lupus.

PMID- 11568248
TI  - Postinfectious glomerulonephritis.

PMID- 11568249
TI  - Membranoproliferative glomerulonephritis.

PMID- 11568250
TI  - Minimal change disease and focal segmental glomerulosclerosis.

PMID- 11568251
TI  - Immunoglobulin A nephropathy.

PMID- 11568252
TI  - Crescentic glomerulonephritis.

PMID- 11568253
TI  - How important is renal biopsy in the management of patients with glomerular
      diseases?

PMID- 11568254
TI  - Nephrotic syndrome in patients with diabetes mellitus is not always associated
      with diabetic nephropathy.

PMID- 11568255
TI  - Early histopathological changes in diabetic nephropathy.

PMID- 11568256
TI  - Lipids, protein intake, and progression of diabetic nephropathy.

PMID- 11568257
TI  - Hypertension and nephropathy in diabetes mellitus: what is inherited and what is
      acquired?

PMID- 11568258
TI  - Management of diabetic patients with haemodialysis, peritoneal dialysis, and
      renal transplantation.

PMID- 11568259
TI  - The prospects of apheresis in the 21st century by new adsorption technologies.

PMID- 11568260
TI  - Therapeutic apheresis in nephrology and neurology.

PMID- 11568261
TI  - Therapeutic apheresis in exogenous poisoning and in myeloma.

PMID- 11568262
TI  - Pathogenesis and management of complications of chronic peritoneal dialysis.

PMID- 11568264
TI  - Peritoneal ultrafiltration failure.

PMID- 11568263
TI  - Prevention and management of peritonitis and exit-site infection in patients on
      continuous ambulatory peritoneal dialysis.

PMID- 11568265
TI  - Pathogenesis and management of malnutrition in chronic peritoneal dialysis
      patients.

PMID- 11568266
TI  - High and low turnover bone disease in patients on chronic peritoneal dialysis.

PMID- 11568267
TI  - Reflux nephropathy in children.

PMID- 11568268
TI  - Diabetic nephropathy in children.

PMID- 11568269
TI  - IgA nephropathy in children.

PMID- 11568270
TI  - Lupus nephropathy in children.

PMID- 11568271
TI  - Uncomplicated urinary tract infections.

PMID- 11568272
TI  - Prostatitis.

PMID- 11568273
TI  - Asymptomatic bacteriuria--clinical significance and management.

PMID- 11568274
TI  - Renal transplantation in Greece.

PMID- 11568275
TI  - Renal transplantation in Turkey.

PMID- 11568276
TI  - Kidney transplantation in Yugoslavia and other Balkan countries.

PMID- 11568277
TI  - Three-year experience with the new Eurotransplant Kidney Allocation System.

PMID- 11568278
TI  - HLA compatibility in organ transplantation.

PMID- 11568279
TI  - The role of HLA class I and class II antibodies in renal transplantation.

PMID- 11568280
TI  - Immunosuppressive regimens for renal transplantation.

PMID- 11568281
TI  - Cardiovascular complications in renal transplantation.

PMID- 11568282
TI  - Getting the NOD to move ahead.

PMID- 11568283
TI  - Resuscitation with 100% oxygen: should we change our ways?

PMID- 11568284
TI  - The impact of corticosteroids on the developing animal.
AB  - Infants are subjected to both endogenous and exogenous corticosteroids in the pre
      and postnatal periods. Stress to the mother before birth, or to the child
      postpartum, can give rise to high, chronic endogenous corticosteroid levels
      caused by activation of the hypothalamic-pituitary-adrenal (HPA) axis. Physician
      administered exogenous corticosteroids are also used in the management of a wide
      spectrum of pre- and postnatal conditions. The long-term effects of
      corticosteroids in developing humans are not well known. Studies in animals,
      however, indicate that both natural stress and exogenous corticosteroids can have
      long-lasting and deleterious effects on the body, brain, behavior, and
      hypothalamic-pituitary-adrenal axis of developing infants. These data suggest
      that exogenous corticosteroids should be administered with caution, after careful
      benefit/risk analyses, and that, as far as possible, the developing brain should
      be protected against the effects of pre- and postnatal stress.

PMID- 11568285
TI  - Tracheal ligation and corticosteroids in congenital diaphragmatic hernia: for
      better for worse?

PMID- 11568286
TI  - Prolonged seizures exacerbate perinatal hypoxic-ischemic brain damage.
AB  - This study was undertaken to clarify whether seizures in the newborn cause damage
      to the healthy brain and, more specifically, to determine the extent to which
      seizures may contribute to the brain-damaging effects of hypoxia-ischemia (HI).
      Seizures were induced in 10-d-old rat pups with kainic acid (KA). Seizure
      duration was determined electrographically. HI was induced by common carotid
      artery ligation followed by exposure to 8% oxygen for either 15 or 30 min. Six
      groups of animals were assessed: 1) controls [neither KA nor HI (group I)]; 2)
      group II, KA alone; 3) group III, 15 min HI alone; 4) group IV,15 min HI plus KA;
      5) group V, 30 min HI alone; and 6) group VI, 30 min HI plus KA. Animals were
      assessed neuropathologically at 3 (early) and 20 (late) d of recovery. KA
      injection without hypoxia resulted in continuous clinical and electrographic
      seizures lasting a mean of 282 min. No neuropathologic injury was seen in groups
      I (no HI or KA), II (KA alone), III (15 min HI alone), or IV (15 min HI and KA).
      Animals in group V (30 min HI alone) displayed brain damage with a mean score of
      2.3 and 0.60 at 3 and 20 d of recovery, respectively. Animals in group VI (30 min
      HI and KA) had a mean score of 12.1 and 3.65 at 3 and 20 d of recovery,
      respectively. Compared with group V, the increased damage as a result of the
      seizure activity in group VI occurred exclusively in the hippocampus. Status
      epilepticus in the otherwise "healthy" neonatal brain does not cause
      neuropathologic injury. However, seizures superimposed on HI significantly
      exacerbate brain injury in a topographically specific manner.

PMID- 11568288
TI  - A novel inhibitor of beta-glucuronidase: L-aspartic acid.
AB  - Infants who consume casein hydrolysate formula have been shown to have lower
      neonatal jaundice levels than infants who consume routine formula or breast milk.
      Because casein hydrolysate has been shown to contain a beta-glucuronidase
      inhibitor, one possible mechanism to explain this finding is blockage of the
      enterohepatic circulation of bilirubin by a component of the formula. The aim of
      this research was to identify the source of the beta-glucuronidase inhibition in
      hydrolyzed casein. A beta-glucuronidase inhibition assay and measurements of
      physical and kinetic parameters were used to analyze the components of hydrolyzed
      casein and infant formulas. Kinetic studies used purified beta-glucuronidase. The
      L-aspartic acid in hydrolyzed casein accounts for the majority of the beta
      glucuronidase inhibition present. Kinetic studies indicate a competitive
      inhibition mechanism. L-aspartic acid is a newly identified competitive inhibitor
      of beta-glucuronidase.

PMID- 11568287
TI  - Effect of a common mutation (D442G) of the cholesteryl ester transfer protein
      gene on lipids and lipoproteins in children.
AB  - Cholesteryl ester transfer protein (CETP) is thought to regulate plasma HDL.
      Patients with CETP deficiency caused by mutation of the CETP gene [D442G; a
      missense mutation (Asp442-->Gly)] have been reported to show high plasma HDL
      levels. However, there are no data available on children with D442G. To determine
      the effects of plasma CETP and CETP gene mutation (D442G) on lipids and
      lipoproteins in children, we screened children by PCR and restriction fragment
      length polymorphism analysis of the CETP gene. Plasma lipids, apolipoproteins,
      and CETP mass levels were also determined. In the current study, 22 children with
      D442G were found (21 heterozygotes and a homozygote). A homozygous child showed
      high plasma HDL level and very low plasma CETP mass. In heterozygous children,
      plasma concentrations of HDL cholesterol, apo A-I and apo A-II were not
      increased, whereas plasma CETP mass was significantly decreased. Plasma CETP mass
      in heterozygous children was correlated with plasma concentrations of total
      cholesterol, LDL cholesterol, and apo B. Plasma CETP mass in children without
      D442G was not correlated with the plasma concentration of any lipid or
      apolipoprotein. All of these data suggest that the D442G mutation, by itself,
      might not affect HDL metabolism in children. The CETP mass required for efficient
      HDL-cholesteryl ester clearance in children may be less than that in older
      subjects.

PMID- 11568289
TI  - Estimation of body fatness by air displacement plethysmography in African
      American and white children.
AB  - The purpose of this study was to determine the ability of air displacement
      plethysmography (ADP) to estimate body fatness in prepubertal and early pubertal
      African American and white children. One hundred nineteen nonoverweight and
      overweight boys (N = 56) and girls (N = 63), age (mean +/- SD) 9.8 +/- 1.7 y,
      body mass index 25.9 +/- 7.6 kg/m2 (range, 14.2-47.0 kg/m2), and mean percent
      body fat (%BF) by dual-energy x-ray absorptiometry (DXA) 39.2 +/- 11.7% (range,
      12.2-57.5%), were studied. %BF by ADP was compared with DXA %BF estimates and
      with body fat by several field methods: skinfold thicknesses using the Slaughter
      et al. equations (Hum Biol 60: 709-723, 1988), bioelectrical impedance analysis
      (BIA) using the Houtkooper et al. equation (J Appl Physiol 72: 366-373, 1992),
      and a predictive equation using skinfold thicknesses, BIA, and weight (Goran et
      al.: Am J Clin Nutr 63: 299-305, 1996). All methods used to estimate %BF were
      significantly correlated with DXA (all p < 0.0001), with r2 ranging from 0.85
      (skinfold measurements) to 0.95 (ADP). ADP using the Siri equation underestimated
      %BF by -1.9% (p < 0.001); the Bland-Altman limits of agreement (defined as +/-2
      SD) were +/-7.4%. %BF by ADP-Siri underestimated %BF by DXA by 3.0% for girls (p
      < 0.001) and by 0.6% for boys (NS). Agreement between body fat estimation by ADP
      and DXA did not vary with age, race, or pubertal stage. Application of the age
      adjusted Lohman model to ADP significantly increased the magnitude of the
      underestimation to -6.9% (p < 0.0001). Prediction of %BF by the Slaughter
      skinfold thickness equation showed no significant mean bias for the overall data,
      but significantly underestimated %BF in girls (-3.7%) while overestimating %BF in
      boys (+2.4%) with wide limits of agreement (+/-17.7%, p < 0.01 versus ADP). %BF
      by the Houtkooper BIA equation or Goran model underestimated %BF to a
      significantly greater degree than ADP (Houtkooper, -8.1%; Goran, -10.1%; both p <
      0.0001 versus DXA or ADP). Determination of %BF from ADP using the Siri model
      slightly underestimates %BF as determined by DXA in girls, but appears to be
      superior to existing field methods both in accuracy and limits of agreement.
      Because of the ease with which it can be performed, ADP may prove useful for
      investigations of adiposity in children.

PMID- 11568290
TI  - Body mass index, body composition, and leptin at onset of puberty in male and
      female rats after intrauterine growth retardation and after early postnatal food
      restriction.
AB  - In this study we examined the body composition at onset of puberty in
      intrauterine growth retarded (IUGR), postnatal food restricted (FR), and control
      male and female rats. IUGR was induced by ligation of the uterine artery on d 17
      of gestation and FR by litter enlargement to 20 pups per mother from d 2 after
      birth until weaning (d 24). We defined onset of puberty as balanopreputial
      separation in male rats and vaginal opening in female rats. We calculated body
      mass index, measured body composition with dual-energy x-ray absorptiometry, and
      measured leptin concentrations in serum. It was reported previously that early
      malnutrition, either during late gestation or immediately postnatally, results in
      a delayed onset of puberty in IUGR and FR male rats and in IUGR female rats, but
      not in FR female rats. In IUGR male rats at balanopreputial separation and in
      IUGR female rats at vaginal opening no differences were found in body mass index,
      body composition, and leptin levels compared with controls. FR male rats had a
      significantly lower percentage of fat and serum leptin concentrations at
      balanopreputial separation. FR female rats had a significantly lower body mass
      index, percentage of fat, and serum leptin concentrations at vaginal opening. We
      conclude that the onset of puberty in the rat is not dependent on a certain
      percentage of body fat or a certain threshold of circulating levels of leptin and
      that food deprivation during different "critical" time periods around birth
      results in different effects in later life.

PMID- 11568291
TI  - Pubertal development in The Netherlands 1965-1997.
AB  - We investigated pubertal development of 4019 boys and 3562 girls >8 y of age
      participating in a cross-sectional survey in The Netherlands and compared the
      results with those of two previous surveys. Reference curves for all pubertal
      stages were constructed. The 50th percentile of Tanner breast stage 2 was 10.7 y,
      and 50% of the boys had reached a testicular volume of 4 mL at 11.5 y of age.
      Median age at menarche was 13.15 y. The median age at which the various stages of
      pubertal development were observed has stabilized since 1980. The increase of the
      age at stage G2 between 1965 and 1997 is probably owing to different
      interpretations of its definition. The current age limits for the definition of
      precocious are close to the third percentile of these references. A high
      agreement was found between the pubic hair stages and stages of pubertal (genital
      and breast) development, but slightly more in boys than in girls. Menarcheal age
      was dependent on height, weight, and body mass index. At a given age tall or
      heavy girls have a higher probability of having menarche compared with short or
      thin girls. A body weight exceeding 60 kg (+1 SDS), or a body mass index of >20
      (+1 SDS), has no or little effect on the chance of having menarche, whereas for
      height such a ceiling effect was not observed. In conclusion, in The Netherlands
      the age at onset of puberty or menarche has stabilized since 1980. Height,
      weight, and body mass index have a strong influence on the chance of menarche.

PMID- 11568292
TI  - Maternal tobacco smoking and lung epithelium-specific proteins in amniotic fluid.
AB  - The bronchiolar 16 kD Clara cell secretory protein (CC16) and the alveolar
      surfactant-associated protein A (SP-A) are secreted in the amniotic fluid (AF),
      where they reflect the growth and the maturity of the fetal lung. To evaluate the
      possible effects of in utero tobacco smoke exposure upon infant bronchoalveolar
      epithelium function and maturity, CC16 and SP-A levels were determined in AF
      obtained at term (36-41 wk) from 28 nonsmoking, 18 smoke-exposed, and 28 smoking
      mothers with uncomplicated pregnancies. Tobacco smoke exposure was assessed by
      questionnaire and the assay in AF and maternal urine of cotinine, a stable
      nicotine metabolite. The specificity of the changes of CC16 and SP-A
      concentrations in AF was assessed by comparison with nonpulmonary proteins of
      high- (albumin and transferrin) or low-molecular weight (beta2-microglobulin,
      retinol binding protein, cystatin-C). Pulmonary and nonpulmonary AF proteins were
      also compared by two-dimensional gel electrophoresis between smoking and
      nonsmoking mothers. The levels of CC16 and SP-A as well as low- and high
      molecular-weight proteins were not significantly different between the three
      smoking categories. The protein pattern of AF, established by two-dimensional gel
      electrophoresis, did not reveal any quantitative or qualitative difference
      between nonsmoking (n = 10), smoke-exposed (n = 5), and smoking mothers (n = 5).
      By multiple regression analysis of possible determinants, tobacco smoke did not
      emerge as a significant predictor of CC16 and SP-A concentrations in AF. SP-A
      level was dependent only on gestational age at birth (r2 = 0.1, p = 0.001),
      whereas CC16 correlated only with the levels of low-molecular weight proteins (r2
      = 0.2, p = 0.0001). The latter correlation suggests that CC16 enters AF not only
      as a result of its secretion at the surface of the respiratory tract but also
      partly following its elimination by the fetal kidney. This study suggests that
      maternal smoking during pregnancy is not associated with alterations of the
      secretory functions of the epithelium of the distal airways and the alveoli at
      term.

PMID- 11568293
TI  - Use of antenatal steroids to counteract the negative effects of tracheal
      occlusion in the fetal lamb model.
AB  - Tracheal occlusion (TO) in fetal lambs induces pulmonary hyperplasia but has
      negative effects on type II cells. The purpose of this study was to determine
      whether antenatal steroids could reverse the adverse effects of TO on lung
      maturation in fetal lambs. Sixteen time-dated pregnant ewes (term, 145 d) and 24
      of their fetuses were divided into six groups: 1) TO at 117 d gestation; 2) TO at
      117 d with a single maternal intramuscular injection of 0.5 mg/kg betamethasone
      24 h before delivery; 3) TO at 117 d and release of the occlusion 2 d before
      delivery; 4) TO and release of the occlusion with maternal steroids; 5)
      unoperated controls without antenatal steroid treatment; and 6) unoperated
      controls, littermates of groups 1-4, treated with antenatal steroids. All fetuses
      were killed at 137 d gestation. Outcome measurements consisted of lung weight-to
      body weight ratio; lung morphometry determined by mean terminal bronchial
      density; and assessment of type II pneumocytes by in situ hybridization to the
      mRNA of surfactant proteins B and C. Lung weight-to-body weight ratio and mean
      terminal bronchial density were significantly different among groups with TO and
      controls, indicating increased lung growth and structural maturation. The density
      of type II pneumocytes was markedly decreased by TO. Release 2 d before sacrifice
      significantly increased the density and surfactant activity of type II
      pneumocytes, but to levels still far from controls. Steroids alone had an effect
      similar to release. An additive effect was noted with steroids and 2-d release
      resulting in type II cell density comparable to controls. After fetal TO, a
      single maternal intramuscular dose of 0.5 mg/kg of betamethasone 24 h before
      delivery allows partial recuperation of the type II pneumocytes, an effect that
      is potentiated by 2-d release.

PMID- 11568294
TI  - Magnetic resonance imaging of pulmonary damage in the term and premature rat
      neonate exposed to hyperoxia.
AB  - Immaturity and oxygen toxicity have been implicated in the pathogenesis of the
      neonatal disease bronchopulmonary dysplasia. The present study aimed to
      investigate the use of magnetic resonance imaging (MRI) to assess hyperoxia
      mediated lung injury in the term and premature neonate. Term (gestation, 22 d)
      and premature (21 d) rat pups were exposed to hyperoxia (>95%) or air for a 6-d
      period (n = 7) and assessed for lung damage by MRI. Pulmonary signal intensities
      of T1-weighted images were significantly increased in both hyperoxia-exposed term
      and premature neonates, relative to air-breathing controls (p < 0.01). T2
      weighted MRI signal intensities were also greater in premature and term rat pups
      exposed to hyperoxia, but failed to reach significance (p > 0.05). Elevated MRI
      pulmonary signal intensities may have represented an increase in magnetic
      resonance-detectable free water, possibly indicating an increase in edema.
      Corresponding histologic evidence of lung injury was detected in both term and
      premature rat pups exposed to hyperoxia. Histologic samples indicated focal
      regions of alveolar hemorrhage, immune cell infiltration, edema, and collapse in
      both term and premature rat neonates exposed to hyperoxia. Alveolar air space was
      assessed (n = 5) by light microscopy within a 0.5 mm2 region of the superior left
      and inferior right pulmonary lobes of each treatment group. Alveolar area of the
      superior left lung lobe of the premature hyperoxia treatment group was
      significantly smaller than other treatment groups (p < 0.05). Reduced area for
      respiratory exchange was probably a result of observed focal areas of edema and
      collapse. MRI-detectable increases in lung signal intensity may have represented
      an increase in hyperoxia-induced pulmonary edema in the 6-d-old rat neonate.
      Increases in signal intensity correlated with the appearance of edema in
      pulmonary histologic samples. Premature delivery had a less defined effect on
      lung injury but possibly exacerbated hyperoxia-mediated pulmonary damage.

PMID- 11568295
TI  - Pulmonary artery vasoconstriction but not [Ca2+]i signal stimulated by
      thromboxane A2 is partially resistant to NO.
AB  - To characterize the thromboxane A2 (TXA2) -induced resistance to the vasodilator
      effects of the nitric oxide (NO)/cGMP pathway in pulmonary arteries, we have
      studied the effects of the NO donor sodium nitroprusside on intracellular calcium
      concentration ([Ca2+]i) and contractile force recorded simultaneously in isolated
      piglet pulmonary arteries loaded with fura-2 and contracted with norepinephrine
      or the TXA2 mimetic U46619 and by activation of protein kinase C (PKC) with
      phorbol 12-myristate 13-acetate. In the TXA2 mimetic- and phorbol 12-myristate 13
      acetate plus norepinephrine-stimulated arteries, nitroprusside exhibited lower
      vasodilator efficacy (and lower potency in the TXA2 mimetic-stimulated arteries)
      but similar reductions in [Ca2+]i compared with arteries activated by
      norepinephrine. The nonselective serine/threonine kinase inhibitor staurosporine,
      but not the selective inhibitor of PKC bisindolylmaleimide, potentiated the
      relaxation of nitroprusside in the TXA2 mimetic-stimulated arteries. In
      conclusion, the resistance to NO/cGMP-induced vasodilation in arteries stimulated
      by TXA2 and PKC involves a reduced ability of the Ca2+-independent mechanisms for
      smooth muscle vasodilation. The resistance to NO in arteries stimulated by TXA2
      is sensitive to staurosporine but not to bisindolylmaleimide, suggesting the
      involvement of an activation of a serine/threonine kinase distinct from PKC.

PMID- 11568296
TI  - Prolonged moderate hyperoxia induces hyperresponsiveness and airway inflammation
      in newborn rats.
AB  - Bronchopulmonary dysplasia is the most common cause of chronic pulmonary disease
      in premature infants. Airway inflammation appears to play a major pathogenetic
      role together with barotrauma and oxygen toxicity. The aim of the present study
      was to determine the effect of a 15-d exposure to moderate hyperoxia (FiO2, 50%)
      on airway reactivity and inflammatory response in neonatal and adult rats. We
      studied in isolated tracheal rings the 1) isometric contraction to cumulative
      concentrations of carbachol (10(-8) to 10(-3) M); 2) epithelial, submucosal,
      smooth muscle, and connective tissue surface area; and 3) distribution of
      inflammatory cells (mastocytes, granulocytes, macrophages) by using MAb.
      Reactivity to carbachol was significantly increased in the hyperoxic pups, in
      which a 13% increase in tracheal smooth muscle surface area was observed. Type-I
      mast cells and macrophages (submucosa and connective tissue) and granulocytes
      (connective tissue) were increased in the neonatal hyperoxic group. Hyperoxia did
      not influence functional, morphometric, or cellular data in adult rats. In
      conclusion, exposure of newborn rats to moderate hyperoxia induces airway
      hyperresponsiveness and histologic changes similar to those reported in
      bronchopulmonary dysplasia. Hyperresponsiveness may be ascribed to an increase in
      smooth muscle related to the release of yet undetermined mediators by
      inflammatory cells infiltrating the airways. Lung immaturity definitely plays a
      role because similar alterations are not observed in adult rats.

PMID- 11568297
TI  - Delayed disaccharidase development in a rabbit model of intrauterine growth
      retardation.
AB  - Intrauterine growth retardation (IUGR) affects almost 10% of infants born in the
      United States. It may be responsible for delayed gastrointestinal function and is
      an important cause of perinatal morbidity and mortality. The New Zealand White
      rabbit provides an optimal model for the study of naturally occurring IUGR. At
      term, birth weight is determined by fetal position within the bicornuate uterus.
      The small intestinal disaccharidase enzymes are indicators of bowel maturity and
      function. To examine potential differences in disaccharidase development between
      normal and IUGR fetuses, this rabbit model was investigated. Jejunum was
      harvested at multiple stages in rabbit development including the third trimester
      fetus, neonate, and adult. Lactase, maltase, and sucrase enzyme activity, as well
      as total protein content, was determined. Results were analyzed by the 2-tailed t
      test and ANOVA. Lactase activity appeared in the mid-third trimester, peaked in
      the early neonatal period, then declined to adult levels. Maltase activity
      appeared in the early third trimester and gradually rose to adult levels. Sucrase
      remained at trace levels until the mid-neonatal period, reaching adult levels by
      weaning. Both lactase and maltase activity were depressed in IUGR fetuses
      compared with their normal littermates. This pattern of disaccharidase depression
      continued into the neonatal period until catch-up growth occurred at 2 wk when
      levels equalized. This report describes differential small intestinal
      disaccharidase development between normal and growth-retarded rabbit fetuses in a
      naturally occurring model of IUGR.

PMID- 11568298
TI  - Hematocrit correlates well with circulating red blood cell volume in very low
      birth weight infants.
AB  - Although circulating red blood cell (RBC) volume is a better measure of total
      body oxygen delivering capacity than hematocrit (HCT), circulating RBC volume is
      more difficult to measure. Thus, the HCT is often used in RBC transfusion
      decisions. However, several previous studies of low birth weight infants have
      reported that the correlation between HCT and circulating RBC volume is poor.
      Using a robust nonradioactive method based on in vivo dilution of biotinylated
      RBC enumerated by flow cytometry, the present study reexamined the correlation
      between HCT and circulating RBC volume in very low birth weight infants. Venous
      and capillary HCT levels were compared with circulating RBC volume measured using
      the biotin method. Twenty-six stable very low birth weight infants with birth
      weights less than 1300 g were studied on 43 occasions between 7 and 79 d of life.
      Venous HCT values correlated highly with circulating RBC volume (r = 0.907; p <
      0.0001). However, the mean 95% confidence limits for prediction of circulating
      RBC volume from venous HCT (the average error of prediction) was +/-13.4 mL/kg.
      The correlation between HCT and circulating RBC volume is strong in older stable
      very low birth weight infants. However, clinically important uncertainty exists
      in estimating circulating RBC volume and the associated RBC transfusion needs of
      an individual infant based on venous HCT. Because direct measurement of
      circulating RBC volume is not yet practical, the HCT (or the blood Hb
      concentration) remains the best available indirect indicator.

PMID- 11568299
TI  - Differing pathogenesis of perinatal bilirubinemia in glucose-6-phosphate
      dehydrogenase-deficient versus-normal neonates.
AB  - The objective was to compare the contribution to perinatal bilirubinemia of
      hemolysis and UDP-glucuronosyltransferase (UGT) gene promoter polymorphism, seen
      in Gilbert's syndrome, between glucose-6-phosphate dehydrogenase (G-6-PD)
      deficient and -normal neonates. Serum total bilirubin (STB) values from 52 G-6-PD
      deficient and 166 G-6-PD-normal term, male neonates, sampled within 3 h of
      delivery (first sample) and on d 3 (second sample), were analyzed in relation to
      blood carboxyhemoglobin corrected for inspired CO (COHbc), an accurate index of
      hemolysis, and UGT promoter genotype. COHbc values (% total Hb) were greater in G
      6-PD-deficient neonates than controls: first sample 1.00 +/- 0.25% versus 0.84 +/
      0.24%, p < 0.0001; second sample 0.83 +/- 0.20% versus 0.76 +/- 0.19%, p =
      0.002. First sample COHbc and STB values did not correlate in either the G-6-PD
      deficient or control groups, whereas second sample COHbc values correlated
      significantly with corresponding STB values in the control population only (r =
      0.28, p = 0.0007). At second sampling, there was a higher allele frequency of the
      variant UGT promoter among those with STB values > or =75th percentile than those
      <75th among the G-6-PD-deficient neonates (0.60 versus 0.33, respectively, p =
      0.025), but not controls (0.31 versus 0.40, respectively, p = 0.24). Among those
      infants with at least one variant UGT promoter allele, STB values were higher in
      the G-6-PD-deficient neonates than controls at second sampling only (181 +/- 56
      microM versus 149 +/- 46 microM, respectively, p = 0.03). Both within and between
      the G-6-PD-deficient and control groups, our data demonstrate changing and
      differing contributions of hemolysis and UGT promoter polymorphism to
      bilirubinemia during the first 3 d of life.

PMID- 11568300
TI  - Surface and cytoplasmic immunoglobulin expression in circulating B-lymphocytes in
      acute Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute vasculitis of young childhood predominantly
      affecting the coronary arteries. IgA plasma cells have been found to infiltrate
      vascular and nonvascular tissues in fatal acute KD. To determine whether IgA B
      lymphocytes were increased in the peripheral blood of patients with KD, we
      performed three-color flow cytometry to detect surface and cytoplasmic
      immunoglobulin expression (IgA, IgM, IgD, and IgG) of peripheral B-lymphocytes in
      KD patients during the acute, subacute, and convalescent stages of illness and in
      age-matched febrile and afebrile pediatric controls. Surprisingly, absolute
      numbers of B-lymphocytes expressing IgA were found to be significantly lower in
      peripheral blood of acute KD patients compared with febrile and afebrile
      pediatric controls. These findings indicate that IgA plasma cells are not present
      in KD tissue as a result of excess numbers of these IgA B-lymphocytes in
      peripheral blood. We speculate that IgA B-lymphocytes are selectively withdrawn
      from the peripheral circulation into KD target tissues as part of a specific IgA
      immune response.

PMID- 11568301
TI  - Circulating adrenomedullin is increased in preterm newborns developing
      intraventricular hemorrhage.
AB  - Adrenomedullin is a novel vasoactive peptide that participates in cerebral blood
      flow regulation and circulates in human plasma. To verify whether plasma
      adrenomedullin is able to identify preterm newborns at risk of intraventricular
      hemorrhage (IVH), we performed a case-control study. Plasma samples collected
      within 6 h after birth in 24 preterm newborns who developed IVH, as diagnosed at
      72 h, were assessed for adrenomedullin and compared with those obtained from 48
      preterm newborns, matched for gestational age, who did not develop IVH. Cerebral
      ultrasound and Doppler velocimetry waveform patterns in the middle cerebral
      artery were also recorded at the time of blood sampling. Adrenomedullin blood
      concentrations and middle cerebral artery pulsatility index values were
      significantly higher in infants developing IVH (20.1 +/- 4.5 fmol/mL and 1.71 +/-
      0.21 fmol/mL, respectively) than in controls (7.5 +/- 3.0 fmol/mL and 1.49 +/-
      0.19 fmol/mL, respectively). Adrenomedullin blood concentrations correlated with
      middle cerebral artery pulsatility index (r = -0.77, p < 0.01) and with the grade
      of IVH extension (r = 0.83, p < 0.01). This study suggests that adrenomedullin
      blood concentration might be a promising tool for identifying preterm infants at
      risk of IVH immediately after birth, when imaging assessment and clinical
      symptoms of hemorrhage are still silent.

PMID- 11568302
TI  - Differentiation genes: are they primary targets for human carcinogenesis?
AB  - In spite of extensive research in molecular carcinogenesis, genes that can be
      considered primary targets in human carcinogenesis remain to be identified.
      Mutated oncogenes or cellular growth regulatory genes, when incorporated into
      normal human epithelial cells, failed to immortalize or transform these cells.
      Therefore, they may be secondary events in human carcinogenesis. Based on some
      experimental studies we have proposed that downregulation of a differentiation
      gene may be the primary event in human carcinogenesis. Such a gene could be
      referred to as a tumor-initiating gene. Downregulation of a differentiation gene
      can be accomplished by a mutation in the differentiation gene, by activation of
      differentiation suppressor genes, and by inactivation of tumor suppressor genes.
      Downregulation of a differentiation gene can lead to immortalization of normal
      cells. Mutations in cellular proto-oncogenes, growth regulatory genes, and tumor
      suppressor genes in immortalized cells can lead to transformation. Such genes
      could be called tumor-promoting genes. This hypothesis can be documented by
      experiments published on differentiation of neuroblastoma (NB) cells in culture.
      The fact that terminal differentiation can be induced in NB cells by adenosine
      3',5'-cyclic monophosphate (cAMP) suggests that the differentiation gene in these
      cells is not mutated, and thus can be activated by an appropriate agent. The fact
      that cAMP-resistant cells exist in NB cell populations suggests that a
      differentiation gene is mutated in these cancer cells, or that differentiation
      regulatory genes have become unresponsive to cAMP. In addition to cAMP, several
      other differentiating agents have been identified. Our proposed hypothesis of
      carcinogenesis can also be applied to other human tumors such as melanoma,
      pheochromocytoma, medulloblastoma, glioma, sarcoma, and colon cancer.

PMID- 11568303
TI  - Role of nitric oxide in central sympathetic outflow.
AB  - The gaseous molecule nitric oxide (NO) plays an important role in cardiovascular
      homeostasis. It plays this role by its action on both the central and peripheral
      autonomic nervous systems. In this review, the central role of NO in the
      regulation of sympathetic outflow and subsequent cardiovascular control is
      examined. After a brief introduction concerning the location of NO synthase (NOS)
      containing neurons in the central nervous system (CNS), studies that demonstrate
      the central effect of NO by systemic administration of NO modulators will be
      presented. The central effects of NO as assessed by intracerebroventricular,
      intracisternal, or direct injection within the specific central areas is also
      discussed. Our studies demonstrating specific medullary and hypothalamic sites
      involved in sympathetic outflow are summarized. The review will be concluded with
      a discussion of the role of central NO mechanisms in the altered sympathetic
      outflow in disease states such as hypertension and heart failure.

PMID- 11568304
TI  - Drug-induced phospholipidosis: are there functional consequences?
AB  - Phospholipidosis induced by drugs with a cationic amphiphilic structure is a
      generalized condition in humans and animals that is characterized by an
      intracellular accumulation of phospholipids and the concurrent development of
      concentric lamellar bodies. The primary mechanism responsible for the development
      of phospholipidosis is an inhibition of lysosomal phospholipase activity by the
      drugs. While the biochemical and ultrastructural features of the condition have
      been well characterized, much less effort has been directed toward understanding
      whether the condition has adverse effects on the organism. While there are a few
      cationic amphiphilic drugs that have been reported to cause phospholipidosis in
      humans, the principal concern with this condition is in the pharmaceutical
      industry during preclinical testing. While this class of drugs should technically
      be referred to as cationic lipophilic, the term cationic amphiphilic is widely
      used and recognized in this field, and for this reason, the terminology cationic
      amphiphilic drugs (CADs) will be employed in this Minireview. The aim of this
      Minireview is to provide an evaluation of the state of knowledge on the
      functional consequences of CAD-induced phospholipidosis.

PMID- 11568305
TI  - Inheritance of resistance to promotion of preneoplastic liver lesions in
      Copenhagen rats.
AB  - Previously, we have shown that Copenhagen (Cop) rats are highly resistant to the
      induction of putative preneoplastic, glutathione S-transferase 7-7- (GST 7-7)
      positive liver lesions following treatment with a modified resistant hepatocyte
      (RH) protocol. The objective of this study was to determine if resistance is
      inherited in a dominant or recessive manner and to derive an estimate of the
      number of genetic loci involved. We crossed male and female Cop rats with F344
      rats to produce F1 offspring. Backcross rats were generated using female F1 rats
      and either Cop or F344 males, resulting in B1c and B1f generations, respectively.
      The male rats from all these crosses were initiated with diethylnitrosamine (200
      mg/kg) at 7 to 8 weeks of age and were promoted 3 weeks later with the RH
      protocol (2-acetylaminofluorene and a two-thirds partial hepatectomy). The rats
      were sacrificed 3 weeks after the partial hepatectomy and their livers were
      sectioned and stained for GST 7-7-positive lesions. The susceptibility of F1 rats
      was in between Cop and F344 rats, having 21.7% +/- 2.0% (mean +/- SEM) of their
      liver volume occupied by lesions versus 4.2% +/- 0.8% for Cop and 53.0% +/- 5.8%
      for F344 rats. As expected, B1c rats had a volume of liver occupied by lesions
      that was in between the F1 and Cop rats at 13.5% +/- 1.6%. Surprisingly, B1f rats
      were similar to B1c rats in their resistance (9.1% +/- 2.1%). These results point
      to a complex, polygenic inheritance pattern that can be explained by a minimum of
      four loci, one of which shows recessive epistasis.

PMID- 11568306
TI  - Effects of selected minerals on leptin secretion in streptozotocin-induced
      hyperglycemic mice.
AB  - The effects of lithium, magnesium, vanadate, and zinc on leptinemia and leptin
      secretion by adipose tissue were investigated in streptozotocin- (STZ) induced
      hyperglycemic mice. After the administration of studied minerals in drinking
      water for 4 weeks, fasting serum leptin concentrations were elevated, accompanied
      by normoglycemia in STZ-injected mice, regardless which mineral was provided (P <
      0.05). However, the in vitro administration of lithium, magnesium, and vanadate
      did not significantly influence the leptin secretion of adipose tissue. A low
      zinc treatment (0.1 mM) augmented, whereas both a pharmacological treatment of
      zinc (1 mM) and zinc depletion (1 mM TPEN) attenuated, leptin secretion (P <
      0.05). The present study shows that STZ-induced hyperglycemic mice have
      hypoleptinemia and reduced leptin secretion by adipose tissue. Moreover, these
      defects can be improved by a moderate zinc administration.

PMID- 11568307
TI  - Zinc deficiency reduces leptin gene expression and leptin secretion in rat
      adipocytes.
AB  - The present study was conducted to measure ob mRNA abundance in the zinc
      deficient (ZD) rats and the secretion of leptin from adipose tissue obtained from
      ZD, zinc-adequate (ZA), and pair-fed (PF) rats. It was found that ob mRNA
      abundance was greatest (P < 0.05) in adipose tissue obtained from ZA and PF rats.
      Ob mRNA abundance was similar in PF and ZD rats. To study leptin secretion from
      adipose tissue in a cell culture model, a method was developed to use excised
      epididymal adipose tissue from ZD, ZA, and PF rats. Tissue was incubated in Opti
      modified Eagle's medium (MEM) cell culture medium in which concentrations of zinc
      and insulin were manipulated. It was observed that leptin secretion was higher (P
      < 0.05) in adipose tissue obtained from ZA than ZD and PF rats. Secretion of
      leptin was higher in adipose tissue of PF than ZD rats (P < 0.05). Surprisingly,
      media zinc content in this ex vivo model tended to suppress secretion of leptin.
      This suppression seems to be zinc specific and might be caused by the
      sequestration of insulin in the culture medium. Our results indicate that the
      reduction in serum leptin observed in ZD rats is likely caused by not only a
      reduction in body fat, but also by a decrease in leptin synthesis and secretion
      per gram of adipose tissue. Taking these results into account along with a prior
      study (1), it is possible that even a marginal zinc deficiency could affect
      leptin secretion and serum leptin concentrations. Impaired leptin secretion
      caused by zinc deficiency might be one factor contributing to hypogonadism
      observed in zinc deficiency.

PMID- 11568308
TI  - Reduced oxygen tension increases atrial natriuretic peptide release from atrial
      cardiocytes.
AB  - To test the hypothesis that reduced oxygen tension stimulates cardiac atrial
      natriuretic peptide (ANP) secretion, we measured ANP release and expression in
      neonatal rat atrial and ventricular cardiac myocytes exposed to 45 min and 3, 6,
      and 24 hr of 3% or 21% oxygen. In atrial cardiocytes, the percentage of increase
      in culture media ANP concentration from baseline was greater in cells exposed to
      3% than in cells exposed to 21% oxygen after 3 hr (814% +/- 52% vs. 567% +/- 33%,
      P < 0.05) and 6 hr of exposure (1639% +/- 91% vs. 1155% +/- 73%, P < 0.05). No
      differences in the percentage of increase in culture media ANP concentration was
      seen at 45 min (284% +/- 27% vs. 201% +/- 16%, P = NS) or 24 hr (2499% +/- 250%
      vs. 2426% +/- 195%). There was a significant increase in cellular ANP content
      between 3 and 24 hr in atrial cardiocytes exposed to 21% oxygen (105% +/- 40% vs.
      296% +/- 60%, P < 0.05), but not in atrial cardiocytes exposed to 3% oxygen (118%
      +/- 20% vs. 180% +/- 26%, P = NS). Steady-state ANP mRNA levels in atrial
      cardiocytes were not affected by oxygen tension. In ventricular cardiocytes,
      oxygen tension did not affect ANP secretion, cellular ANP content, or steady
      state ANP mRNA levels. We conclude that reduced oxygen tension increases release
      of ANP from atrial, but not ventricular cardiocytes and that this mechanism may
      contribute to the elevation in plasma ANP seen during acute hypoxia.

PMID- 11568309
TI  - Maximum life spans in mice are extended by wild strain alleles.
AB  - The genes that control basic aging mechanisms in mammals are unknown. By using
      two four-way crosses, each including a strain derived from wild, undomesticated
      stocks, we identified two quantitative trait loci that extend murine life spans
      by approximately 10%. In one cross, the longest-lived 18% of carriers of the
      D8Mit171 marker allele from the MOLD/Rk strain, Mus m. molossinus, outlived the
      longest lived 18% of noncarriers by 129 days (P = 5.4 x 10(-5)); in a second
      cross, carriers of the D10Mit267 allele from the CAST/Ei strain, Mus m.
      castaneus, outlived noncarriers by 125 days ( P = 1.6 x 10(-6)). In both crosses,
      P < 1.0 x 10(-4 )is considered significant. Because these life span increases
      required that all essential biological systems function longer than normal, these
      alleles most likely retarded basic aging mechanisms in multiple biological
      systems simultaneously.

PMID- 11568310
TI  - The vasorelaxation of cerebral arteries by carbon monoxide.
AB  - Carbon monoxide (CO) is known to increase cerebral blood flow, but the effect of
      CO on the vascular tone of large cerebral arteries is uncertain. We tested
      whether CO affects cerebral artery tone by measuring tension generated by ex vivo
      segments of dog basilar artery upon exposure to CO. In cerebral artery segments
      contracted with either KCl or prostaglandin F(2alpha), CO caused a concentration
      related relaxation beginning with a concentration of 57 microM. Relaxation did
      not occur if CO was administered in the presence of bubbling carboxygen (95%
      O(2):5% CO(2)), which reduces greater than 99% of CO from the solution.
      Furthermore, the CO-induced relaxation of cerebral artery segments was reduced in
      the presence of the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ, 10 microM)or the potassium channel blocker
      tetraethylammonium (TEA, 1 mM). Neither ODQ nor TEA completely eliminated the
      relaxation caused by CO and there was no additive effect if ODQ and TEA were
      administered together. These results suggest that cerebral arteries are directly
      relaxed by CO and that this relaxation depends upon the activation of guanylyl
      cyclase and the opening of potassium channels.

PMID- 11568311
TI  - Erythrocytic glutathione and plasma cysteine status of human immunodeficient
      patients.
AB  - Both deficient and normal blood levels of glutathione (GSH) and cysteine (Cys)
      have been reported in HIV patients, a discrepancy that has been attributed to
      different methodologies. The goal of this study was to apply our analytical
      method to this problem. Blood samples from HIV patients and healthy subjects were
      collected, immediately stabilized, and quantified using high performance liquid
      chromatography with dual electrochemical detection. The results showed that the
      erythrocytic GSH levels were the same in healthy subjects and in HIV patients
      regardless of their CD4 lymphocyte level. Only those with the lowest CD4 level
      plus opportunistic infections had supranormal [corrected] GSH concentrations (P <
      0.001). GSH plus glutathione disulfide (GSSG) levels also were normal in
      patients. However, the Cys contents were higher in patients than in controls (P <
      0.05). These findings demonstrated that HIV patients have normal erythrocytic GSH
      concentrations and supranormal Cys levels.

PMID- 11568312
TI  - Instructional technology and radiologic education.

PMID- 11568315
TI  - CT angiography of the lower extremities and aortoiliac system with a multi
      detector row helical CT scanner: promise of new opportunities fulfilled.

PMID- 11568316
TI  - Radio-frequency coil selection for MR imaging of the brain and skull base.
AB  - Radio-frequency coils play a crucial role in the quest for optimal magnetic
      resonance (MR) image resolution. Given the growing variety of specialized coils
      available for neuroradiologic imaging applications, it is critical that
      radiologists use a coherent strategy for successfully matching these coils to
      specific imaging situations. First, fundamental concepts of coil design are
      reviewed. Subsequently, a coil-selection algorithm for neuroimaging applications
      is described. The algorithm uses the patient's clinical history to derive a
      region of interest, a desired spatial resolution, and a desired contrast
      resolution. These factors are then used to impose anatomic coverage and imaging
      protocol constraints on the set of available coils. Finally, coil selection is
      further refined according to patient tolerance factors. The following coils are
      considered for use with a 1.5-T superconducting MR imager; namely, quadrature
      birdcage head, neurovascular phased-array, and dual single-circular-element
      coils, as well as investigational coils that have not yet been approved by the
      U.S. Food and Drug Administration: reduced-volume birdcage end-cap, temporal lobe
      phased-array, carotid artery phased-array, coils. Rationales are discussed
      regarding appropriate coil selection for screening whole brain and imaging
      brainstem, cranial nerves, orbits, cerebral cortex, mesial temporal lobes, and
      internal auditory canal, and for MR angiography.

PMID- 11568317
TI  - Ischemic stroke: effects of etiology and patient age on the time course of the
      core apparent diffusion coefficient.
AB  - PURPOSE: To determine whether the evolution of the core apparent diffusion
      coefficient (ADC) of water in ischemic stroke varies with patient age or infarct
      etiology. MATERIALS AND METHODS: One hundred forty-seven patients with stroke
      underwent 236 diffusion-weighted magnetic resonance imaging examinations.
      Etiologies of lesions were classified according to predefined criteria; in 224
      images, the diagnosis of lacune could be firmly established or excluded. ADC was
      measured in the center of each lesion and in contralateral normal-appearing
      brain. A model was used to describe the time course of relative ADC (rADC), which
      is calculated by dividing the lesion ADC by the contralateral ADC, and to test
      for age- or etiology-related differences in this time course. RESULTS: Transition
      from decreasing to increasing rADC was estimated at 18.5 hours after stroke
      onset. In subgroup analysis, transition was earlier in nonlacunes than in lacunes
      (P =.02). There was a trend toward earlier transition in patients older than the
      median age of 66.0 years, compared with younger patients (P =.06).
      Pseudonormalization was estimated at 216 hours. Among nonlacunes, the rate of
      subsequent rADC increase was more rapid in younger patients than in older
      patients (P =.001). Within the smaller sample of lacunes, however, no significant
      age-related difference in this rate was found. CONCLUSION: Differences in ADC
      depending on the patient's age and infarct etiology suggest differing rates of
      ADC progression.

PMID- 11568318
TI  - Time course of cerebral infarction in the middle cerebral arterial territory:
      deep watershed versus territorial subtypes on diffusion-weighted MR images.
AB  - PURPOSE: To examine possible differences between the evolution of cerebral
      watershed infarction (WI) and that of territorial thromboembolic infarction (TI)
      by using diffusion-weighted (DW) and T2-weighted magnetic resonance (MR) images
      and apparent diffusion coefficient (ADC) maps. MATERIALS AND METHODS: Fourteen
      patients with TI and nine with WI underwent MR imaging from the acute to chronic
      infarction stages. ADC maps were derived from DW images. Lesion-to-normal tissue
      signal intensity ratios on ADC maps (rADC), echo-planar T2-weighted images, and
      DW images were calculated. Lesion volumes at acute or early subacute infarction
      stages were measured on DW images, and final lesion volumes were estimated on
      fluid-attenuated inversion-recovery images. RESULTS: Analysis of variance
      revealed a significant difference in temporal evolution patterns of rADC between
      WI and TI (P <.001). rADC pseudonormalization following TI began about 10 days
      after symptom onset, but that following WI did not occur until about 1 month
      after symptom onset. The Pearson correlation coefficient between final and
      initial infarct volumes was 0.9899 for both infarction subtypes, indicating that
      the initial ischemic injury volume measured at the acute or early subacute stage
      predicted the final lesion volume fairly well. CONCLUSION: The evolution time of
      ADC is faster for TI than for WI. This difference, which likely originates from
      the different pathophysiologic and hemodynamic features of the two infarction
      types, might account for the relatively large range of ADC values reported for
      the time course of ischemic strokes.

PMID- 11568319
TI  - Frequency and clinical context of decreased apparent diffusion coefficient
      reversal in the human brain.
AB  - PURPOSE: To determine the probability that regions of decreased apparent
      diffusion coefficient (ADC) return to normal without persistent symptoms or T2
      change and the settings in which these ADC reversals occur. MATERIALS AND
      METHODS: Three hundred magnetic resonance (MR) imaging studies were selected at
      random from a database of 7,147 examinations to determine the probability of a
      pathologically decreased ADC. In cases with decreased ADC, the clinical history
      was recorded and, if available, follow-up MR imaging findings were evaluated.
      Five cases of ADC reversal became known during the same period and were evaluated
      to determine the initial ADC decrease, clinical outcome, and findings at follow
      up imaging. RESULTS: Findings in 116 of 300 MR imaging studies revealed regions
      of decreased ADC. In 49 of 116 studies, follow-up MR imaging examinations were
      performed at least 4 weeks after the onset of symptoms; ADC did not reverse. Five
      cases of ADC reversal were identified in the same period, giving an estimated
      0.2%-0.4% probability of ADC reversal. Clinical settings were venous sinus
      thrombosis and seizure (n = 3), hemiplegic migraine (n = 1), and hyperacute
      arterial infarction (n = 1). Both white matter (n = 3) and gray matter (n = 3)
      regions were involved. CONCLUSION: Reversal of ADC lesions is rare, occurs in
      complicated clinical settings, and can involve white or gray matter.

PMID- 11568320
TI  - Neuropsychologic correlates of brain white matter lesions depicted on MR images:
      1921 Aberdeen Birth Cohort.
AB  - PURPOSE: To examine relationships between brain white matter hyperintensities
      depicted at magnetic resonance (MR) imaging and performance on neuropsychologic
      tests in community-dwelling elderly adults. MATERIALS AND METHODS: The 1921
      Aberdeen Birth Cohort is a subsample of survivors of the Scottish Mental Survey
      of 1932 whose mental ability was tested at 11 years of age. Ninety-five of these
      subjects agreed to undergo brain MR imaging, an examination of general health,
      and a neuropsychologic evaluation. White matter hyperintensities detected at T2
      weighted MR imaging were rated by using a semiquantitative method yielding two
      continuous variables: white matter lesions and periventricular lesions. Cognitive
      ability, including crystallized and fluid intelligence domains, was assessed with
      standard neuropsychologic tests. RESULTS: Rating scores of white matter lesions
      were normally distributed (on a devised scale) with means of 1.14 for white
      matter lesions and 1.28 for periventricular lesions. Intra- and interobserver
      reliability coefficients for scores were high, generally above 0.7. There were
      significant correlations of medium effect size between the T2-weighted MR imaging
      depicted white matter lesions and performance on tests of fluid-type
      intelligence. No significant correlation was demonstrated between white matter
      lesion ratings and tests of crystallized intelligence. CONCLUSION: Lower fluid
      type ("prevailing") intelligence test scores were associated with increased
      severity of white matter lesion ratings but not crystallized-type ("premorbid")
      intelligence test scores. This indicates that MR imaging-depicted white matter
      lesions are of clinical importance.

PMID- 11568321
TI  - Brain activation in sedated children: auditory and visual functional MR imaging.
AB  - PURPOSE: To map developing areas of activation with functional magnetic resonance
      (MR) imaging in sedated children by using passive auditory and visual tasks.
      MATERIALS AND METHODS: Forty children between 2 months and 9 years old were
      examined and grouped according to age. Children were selected from patients
      referred to undergo brain MR imaging. Patients received pentobarbital (3.0-7.0 mg
      per kilogram of body weight) or chloral hydrate (50-75 mg/kg). The functional MR
      imaging study was performed at the end of the examination. Paradigms consisted of
      flashing lights at 8 Hz displayed on special goggles and a prerecorded mother's
      voice presented through headphones. Activation maps were obtained from a paired t
      test with a P value of.0005 (uncorrected). RESULTS: The visual stimulus produced
      statistically significant negative values in the rostral aspect of the primary
      visual area (28 [90%] of 31 patients). The auditory paradigm activated either
      temporal or frontal areas in 26 (68%) of 31 patients. There was more frontal
      activation in the older children. CONCLUSION: Visual and auditory cortices can be
      activated in children who have been sedated. Visual responses show negative
      values in the rostral visual cortex, independent of age. Auditory activation is
      seen in temporal and frontal lobes.

PMID- 11568322
TI  - Coats disease: smaller volume of the affected globe.
AB  - PURPOSE: To determine whether a significant smaller volume of the affected globe,
      compared with that of the normal globe, is an additional feature of Coats
      disease. MATERIALS AND METHODS: Ocular globe volume was assessed in 13 children
      (11 boys, two girls; age range, 0.6-14 years; mean age, 4.1 years) with Coats
      disease and in 18 (eight boys, 10 girls; age range, 0.5-12 years; mean age, 3.6
      years) with unilateral retinoblastoma. Orbital computed tomographic scans were
      available for all children; magnetic resonance images were available for 11
      children-seven with Coats disease and four with retinoblastoma. For volume
      estimation, anteroposterior and equatorial diameters of ocular globes were
      measured. Statistical analysis was conducted with univariate and multivariate
      methods. RESULTS: In children with Coats disease, the mean volume of the affected
      globe was 4,877.03 mm(3) (range, 2,951.47-6,284.70 mm(3)) and that of the normal
      globe, 6,018.00 mm(3) (range, 4,062.32-7,509.26 mm(3)). In children with
      retinoblastoma, the mean volume of the affected globe was 4,557.06 mm(3) (range,
      1,612.01-7,463.00 mm(3)) and that of the normal globe, 4,402.11 mm(3) (range,
      1,360.46- 7,463.00 mm(3)). The Coats disease population had a significantly
      smaller volume of the affected globe (z = -3.1009; P =.002); the retinoblastoma
      population did not have a statistically significant trend toward a bigger
      affected globe volume (z = -1.7064; P =.088). The difference between the affected
      globe volume and the normal globe volume in children with Coats disease was the
      only significant independent variable (P =.005). CONCLUSION: A significantly
      smaller volume of the affected globe is an additional feature of Coats disease.

PMID- 11568323
TI  - Fetal cerebellum: US appearance with advancing gestational age.
AB  - PURPOSE: To evaluate the change in ultrasonographic (US) appearance of the fetal
      cerebellum with advancing gestation. MATERIALS AND METHODS: A total of 291 normal
      fetuses of uncomplicated pregnancies were evaluated at gestational ages (GAs)
      between 15 and 41 weeks with a 3.75-MHz transabdominal curvilinear probe. After
      the transcerebellar view was obtained, the transverse cerebellar diameter (TCD)
      was measured and the images were stored. On hard-copy US images, cerebella were
      assigned three grades of appearance. These grades were analyzed in relation to GA
      and TCD. Inter- and intraobserver variations were assessed in 91 randomly
      selected cases. RESULTS: Cerebella in 137 (47.1%), 71 (24.4%), and 83 (28.5%) of
      291 subjects were classified as grade I (hypoechoic, "eyeglass" shape), grade II
      (intermediate echogenicity, "dumbbell" outline), and grade III (hyperechoic,
      "fan" shape), respectively. With advancing gestation, the dominant grade changed
      from I to III gradually and progressively. The median GA and TCD, respectively,
      were 22 weeks and 22 mm for grade I, 29 weeks and 35 mm for grade II, and 36
      weeks and 46 mm for grade III. These differences were statistically significant
      (P <.001). The agreements within inter- and intraobserver estimations were 96%
      (87 of 91) and 95% (86 of 91), respectively. CONCLUSION: A gradual change in US
      appearance of the fetal cerebellum is seen with advancing gestation.

PMID- 11568324
TI  - Changes in myometrial and junctional zone thickness and signal intensity:
      demonstration with kinematic T2-weighted MR imaging.
AB  - PURPOSE: To demonstrate uterine contractions by evaluating changes during time in
      the thickness of the myometrium and junctional zone and in signal intensity of
      the uterus with T2-weighted fast magnetic resonance (MR) images in a kinematic
      fashion. MATERIALS AND METHODS: Sagittal MR imaging was performed with T2
      weighted fast spin-echo (FSE) and multiphase-multisection single-shot FSE (SSFSE)
      in 60 premenopausal patients during free breathing. SSFSE MR images were
      evaluated with cine display. The pattern of uterine contractions and changes in
      signal intensities of the uterine structures were evaluated. Thickness of both
      myometrium and junctional zone, and their signal intensities, were measured
      during 15 phases of SSFSE and FSE MR imaging. RESULTS: Slow-massive (mean, 55%),
      middle-cycle (mean, 80%), and fine (mean, 93%) contractions were observed. Shape
      of junctional zones dynamically changed during time, showing focal (mean, 58%)
      and diffuse (mean, 82%) thickening and wavelike motions (mean, 88%). Ratio of
      thickness of the myometrium to junctional zone with FSE MR imaging was not
      significantly different from the mean ratio during 15 phases of SSFSE MR imaging,
      although maximum percentage of change of the ratio during 15 phases was 42.5%
      56.8%. The signal intensities of the myometrium (97%) and junctional zone (75%)
      changed during time. CONCLUSION: Kinematic T2-weighted SSFSE MR images
      demonstrate uterine contractions related to dynamic changes in thickness and
      signal intensities of the myometrium and junctional zone, and these findings
      might affect the diagnosis of uterine disease.

PMID- 11568325
TI  - Relative attractiveness of diagnostic radiology: assessment with data from the
      National Residency Matching Program and comparison with the strength of the job
      market.
AB  - PURPOSE: To quantify medical students' preferences for various specialties and to
      compare shifts in specialty preference with overall employment market prospects.
      MATERIALS AND METHODS: By using National Residency Matching Program data, a
      previously validated help-wanted index (HWI), and American Medical Association
      (AMA) salary data, the authors quantified medical students' preferences for
      various specialties and examined the association of shifts in specialty
      preference with overall trends as seen in the strength of the diagnostic
      radiology match and its relationship with the job market. The authors established
      a proxy for the relative attractiveness (RA) of diagnostic radiology (relative to
      all specialties) in the match, which was calculated by subtracting the percentage
      fill rate for all specialties from that for radiology. The RA values were plotted
      for 1990-2000 and compared with trends in the HWI, American College of Radiology
      data, and AMA salary data. RESULTS: The RA of diagnostic radiology varied greatly
      during the past 10 years, with a low in 1996 and a return to its high in recent
      years. There is a relationship between the RA and economic vitality of diagnostic
      radiology, with the RA lagging behind the HWI and AMA salary data by 2 years.
      CONCLUSION: Medical students appear to have an in-depth understanding of the
      economic forces at play in the health care job market and incorporate this
      information into their choice of a specialty.

PMID- 11568326
TI  - Pancreatic cancer: cost-effectiveness of imaging technologies for assessing
      resectability.
AB  - PURPOSE: To evaluate the cost-effectiveness of imaging strategies for the
      assessment of resectability in patients with pancreatic cancer. MATERIALS AND
      METHODS: A decision model was developed to calculate costs and benefits
      (survival) accruing to hypothetical cohorts of patients with known or suspected
      pancreatic cancer. Results are presented as cost per life-year gained under
      various scenarios and assumptions of diagnostic test characteristics, surgical
      mortality, disease characteristics, and costs. RESULTS: With best estimates for
      all data inputs, the strategy of computed tomography (CT) followed by laparoscopy
      and laparoscopic ultrasonography (US) had an incremental cost-effectiveness ratio
      of $87,502 per life-year gained, compared with best supportive care. This
      strategy was significantly more cost-effective than CT followed by magnetic
      resonance (MR) imaging and was significantly less expensive than other imaging
      strategies while providing a statistically and clinically insignificant
      difference in life-year gains. A strategy involving no imaging (immediate
      surgery) was more expensive but less effective than all imaging strategies. A
      hypothetical perfect test with cost equal to that of CT followed by MR had an
      incremental cost-effectiveness ratio of $64,401 per life-year gained, compared to
      best supportive care. CONCLUSION: Most available imaging tests for assessing
      resectability of pancreatic cancer do not differ in effectiveness, but a strategy
      of CT, laparoscopy, and laparoscopic US would consistently result in
      significantly lower costs than other imaging tests under a wide range of
      scenarios.

PMID- 11568327
TI  - Duct-penetrating sign at MRCP: usefulness for differentiating inflammatory
      pancreatic mass from pancreatic carcinomas.
AB  - PURPOSE: To define the duct-penetrating sign at magnetic resonance (MR)
      cholangiopancreatography (MRCP) and to assess the usefulness of this sign for
      distinguishing an inflammatory pancreatic mass (IPM) from a conventional
      pancreatic carcinoma (CPC) compared with arterial phase computed tomography
      (hereafter, CT) and arterial phase MR imaging (hereafter, MR imaging). MATERIALS
      AND METHODS: MRCP, CT, and MR images were compared by means of receiver operating
      characteristic (ROC) analysis for 11 IPMs and 43 CPCs. With the MRCP images, a
      morphologic classification of the main pancreatic duct (MPD) was attempted for
      all lesions. On the basis of this classification and the enhancement patterns of
      a lesion, all readers graded the presence of IPM or CPC on a five-point scale for
      all images. RESULTS: On the MRCP images, the morphologic characteristics of the
      MPD were nonobstruction for IPM (28 of 33, 85%) and obstruction or irregular
      stenosis for CPC (124 of 129, 96%). At ROC analysis among all the techniques,
      MRCP images had the highest value (0.98) for significant areas under the ROC
      curve (CT, 0.84; MR, 0.76) (P <.001). For the duct-penetrating sign in the broad
      sense (nonobstructed MPD) and the sign in the narrow sense (only normal MPD), the
      sensitivity, specificity, and accuracy for diagnosis of IPM were 85%, 96%, and
      94%, respectively, and 36%, 100%, and 87%, respectively. CONCLUSION: The duct
      penetrating sign on MRCP images was more helpful to distinguish IPM from CPC than
      were the enhancement patterns on CT and MR images.

PMID- 11568328
TI  - Diffuse desmoplastic breast carcinoma metastases to the liver simulating
      cirrhosis at MR imaging: report of two cases.
AB  - Two patients with breast carcinoma, without a prior diagnosis of liver lesions,
      had proved desmoplastic hepatic metastases that resembled cirrhosis at magnetic
      resonance (MR) imaging. The cirrhotic appearance of the livers may have resulted
      from the hepatotoxic effects of chemotherapy and/or hepatic infiltration by the
      metastatic tumor itself. Despite its high soft-tissue contrast, MR imaging may
      fail to depict extensive metastases from breast carcinoma, especially when they
      simulate other diseases (eg, cirrhosis). Correlation of MR imaging findings with
      clinical history is mandatory.

PMID- 11568329
TI  - Blinded review of retrospectively visible unreported breast cancers: an eye
      position analysis.
AB  - PURPOSE: To determine whether unreported retrospectively identified cancers on
      mammograms receive prolonged visual attention and can be reliably detected in a
      blinded review. MATERIALS AND METHODS: Four experienced mammographers performed a
      blinded review of a test set of 20 retrospective cases where the cancer was not
      detected until the next mammographic evaluation, 10 prospective cases where the
      cancer was initially detected, and 10 cancer-free cases. Two views were digitized
      and displayed on a workstation. The experiment consisted of an initial
      impression, during which eye position was monitored, and a final impression,
      during which viewers zoomed on regions of interest and localized suspicious
      lesions. Eye-position data were analyzed to determine whether retrospectively
      visible cancers attracted attention to the same degree as prospectively visible
      cancers. The initial impression used 1,000 msec as the eye-fixation dwell
      criterion for detecting a lesion. RESULTS: Initially, 70% of retrospective
      cancers and 50% of prospective cancers did not attract prolonged visual
      attention. In prospective cases, detailed examination significantly improved the
      mean receiver operating characteristic area, from.73 to.88 (P <.01), but in
      retrospective cases, the mean receiver operating characteristic area barely
      increased, from.60 to.68, due to a high true-positive-to-false-positive ratio.
      CONCLUSION: At blinded review, detection of retrospectively visible cancers was
      significantly inferior to that of prospective cancers. It cannot be assumed that
      retrospectively identified cancers are intrinsically detectable, because they do
      not draw prolonged visual attention during visual search for breast cancers.

PMID- 11568331
TI  - Case 39: invasive lobular carcinoma.

PMID- 11568332
TI  - Balloon dilation and stent implantation for treatment of femoropopliteal arterial
      disease: meta-analysis.
AB  - PURPOSE: To perform a meta-analysis of long-term results of balloon dilation and
      stent implantation in the treatment of femoropopliteal arterial disease.
      MATERIALS AND METHODS: The English-language literature was searched for studies
      published between 1993 and 2000. Inclusion criteria for articles were
      presentation of long-term primary patency rates, standard errors (explicitly
      reported or derivable), and baseline characteristics of the study population. Two
      reviewers independently extracted data, and discrepancies were resolved by
      consensus. Primary patency rates were combined by using a technique that allows
      adjustment for differences across study populations. Analyses were adjusted for
      lesion type and clinical indication. RESULTS: Nineteen studies met the inclusion
      criteria, representing 923 balloon dilations and 473 stent implantations.
      Combined 3-year patency rates after balloon dilation were 61% (standard error,
      2.2%) for stenoses and claudication, 48% (standard error, 3.3%) for occlusions
      and claudication, 43% (standard error, 4.1%) for stenoses and critical ischemia,
      and 30% (standard error, 3.7%) for occlusions and critical ischemia. The 3-year
      patency rates after stent implantation were 63%-66% (standard error, 4.1%) and
      were independent of clinical indication and lesion type. Funnel plots
      demonstrated an asymmetric distribution of the data points associated with stent
      studies. CONCLUSION: Balloon dilation and stent implantation for claudication and
      stenosis yield similar long-term patency rates. For more severe femoropopliteal
      disease, the results of stent implantation seem more favorable. Publication bias
      could not be ruled out.

PMID- 11568333
TI  - Multi-detector row CT angiography of lower extremity arterial inflow and runoff:
      initial experience.
AB  - PURPOSE: To assess the patterns of lower extremity arterial inflow and runoff
      opacification with four-channel multi-detector row computed tomographic (CT)
      angiography in a cohort of patients with disease warranting imaging of the lower
      extremity arterial system. MATERIALS AND METHODS: Twenty-four patients with
      symptomatic lower extremity arterial occlusive or aneurysmal disease underwent
      imaging with four-channel multi-detector row CT from the supraceliac abdominal
      aorta through the feet. Transverse sections were acquired with a 2.5-mm nominal
      detector width and pitch of 6.0 (3.2-mm effective section thickness) following
      intravenous injection of 174-185 mL of iodinated contrast medium (300 mg iodine
      per milliliter). In each patient, attenuation measurements were recorded in 16
      arterial and 16 venous locations. In 18 patients, two radiologists assessed the
      detectability and stenosis degree of 21 arterial segments per patient relative to
      these features at conventional angiography. RESULTS: A mean scanning time of 66
      seconds was required to cover a mean of 1,233 mm, resulting in a mean of 908
      transverse reconstructions. All 504 arterial segments were depicted and
      analyzable. Mean arterial attenuation ranged from 253 HU in the midabdominal
      aorta to 357 HU in the popliteal artery and 253 HU in the dorsalis pedis or
      posterior tibial artery measured inferior to the tibiotalar joint. Maximum mean
      venous enhancement (99 HU) was observed in the saphenous vein at the ankle, with
      all other venous stations measuring less than 74 HU. CONCLUSION: The arteries of
      lower extremity inflow and runoff can be reliably depicted with minimal venous
      enhancement by using multi-detector row CT.

PMID- 11568334
TI  - Percutaneous radio-frequency ablation of hepatic metastases from colorectal
      cancer: long-term results in 117 patients.
AB  - PURPOSE: To describe the results of an ongoing radio-frequency (RF) ablation
      study in patients with hepatic metastases from colorectal carcinoma. MATERIALS
      AND METHODS: In 117 patients, 179 metachronous colorectal carcinoma hepatic
      metastases (0.9-9.6 cm in diameter) were treated with RF ablation by using 17
      gauge internally cooled electrodes. Computed tomographic follow-up was performed
      every 4-6 months. Recurrent tumors were retreated when feasible. Time to new
      metastases and death for each patient and time to local recurrence for individual
      lesions were modeled with Kaplan-Meier analysis. Modeling determined the effect
      of number of metastases on the time to new metastases and death and effect of
      tumor size on local recurrence. RESULTS: Estimated median survival was 36 months
      (95% CI; 28, 52 months). Estimated 1, 2, and 3-year survival rates were 93%, 69%,
      and 46%, respectively. Survival was not significantly related to number of
      metastases treated. In 77 (66%) of 117 patients, new metastases were observed at
      follow-up. Estimated median time until new metastases was 12 months (95% CI; 10,
      18 months). Percentages of patients with no new metastases after initial
      treatment at 1 and 2 years were 49% and 35%, respectively. Time to new metastases
      was not significantly related to number of metastases. Seventy (39%) of 179
      lesions developed local recurrence after treatment. Of these, 54 were observed by
      6 months and 67 by 1 year. No local recurrence was observed after 18 months.
      Frequency and time to local recurrence were related to lesion size (P < or
      =.001). CONCLUSION: RF ablation is an effective method to treat hepatic
      metastases from colorectal carcinoma.

PMID- 11568335
TI  - Hepatocellular carcinoma: US-guided percutaneous microwave coagulation therapy.
AB  - PURPOSE: To evaluate the use of percutaneous microwave coagulation therapy for
      hepatocellular carcinoma, particularly with tumor nodules larger than 2 cm in
      diameter. MATERIALS AND METHODS: Fifty patients with 107 hepatocellular carcinoma
      nodules (mean diameter, 2.7 cm +/- 1.5 [SD]; range, 0.8-6.4 cm) were treated with
      percutaneous microwave coagulation therapy. Single electrode insertion was used
      in 46 nodules (43.0%) 2 cm or smaller, whereas multiple electrode insertion was
      applied in 61 (57.0%) nodules larger than 2 cm. RESULTS: At 1 month after
      therapy, technical success for tumors 2 cm or smaller and those larger than 2 cm
      was achieved in 45 (98%) and 56 (92%) nodules, respectively. After follow-up of 9
      months or longer, local recurrence was found in one nodule (2%) sized 1.8 cm and
      in five nodules (8%) larger than 2 cm. At the end of the study, 26 (52%) of 50
      patients were free of disease, and disease-free survival rates at 1 and 2 years
      were 55% and 41%, respectively. Overall survival rates at 1, 2, and 3 years were
      96%, 83%, and 73%, respectively. CONCLUSION: Percutaneous microwave coagulation
      therapy is an effective and safe therapeutic modality for hepatocellular
      carcinoma. A multiple electrode insertion technique can enhance the effectiveness
      of this therapy in tumors 6 cm or smaller.

PMID- 11568336
TI  - Peritoneal carcinomatosis: image-guided peritoneal core biopsy for tumor type and
      patient care.
AB  - PURPOSE: To assess image-guided peritoneal core biopsy for the diagnosis of tumor
      type and treatment of patients with peritoneal carcinomatosis. MATERIALS AND
      METHODS: Thirty-five women (age range, 47-85 years; mean age, 69 years)
      prospectively identified in a gynecologic oncology center underwent 18-gauge core
      biopsy in omental cake (n = 25), peritoneal (n = 7), or adnexal (n = 3) sites. No
      complications of biopsy occurred. Standard hematoxylin-eosin analysis of the
      biopsy cores was supplemented by immunohistochemical markers to CA-125,
      carcinoembryonic antigen, cytokeratin 7, and cytokeratin 20. Diagnoses were
      validated with further multidisciplinary review, subsequent surgery, and response
      to specific chemotherapy. RESULTS: In 27 (77%) of the 35 women, a confident
      primary site diagnosis was obtained with standard hematoxylin-eosin analysis of
      core biopsy material from the following sites: ovary (n = 22), breast (n = 2),
      colon (n = 2), and lymphoma (n = 1). The finding at hematoxylin-eosin analysis in
      another seven (20%) women was poorly differentiated adenocarcinoma with no
      definite primary site but with an immunohistochemical profile suggesting ovarian
      cancer (CA-125 positive, carcinoembryonic antigen negative, cytokeratin 7
      positive, cytokeratin 20 negative). There was one false-negative biopsy result.
      CONCLUSION: Image-guided peritoneal core biopsy with hematoxylin-eosin analysis
      supplemented with immunohistochemical analysis is a simple, safe, and accurate
      technique for providing site-specific diagnoses in women with undiagnosed
      peritoneal carcinomatosis.

PMID- 11568337
TI  - Lumbar facet joint synovial cyst: percutaneous treatment with steroid injections
      and distention--clinical and imaging follow-up in 12 patients.
AB  - PURPOSE: To determine the imaging characteristics of lumbar facet joint synovial
      cysts after percutaneous treatment with steroid injections and distention of the
      cyst and to correlate these findings with the clinical outcome. MATERIALS AND
      METHODS: Clinical outcome and imaging findings were retrospectively studied in 12
      patients (four men, eight women) aged 45-79 years (mean, 60 years) with a
      symptomatic lumbar facet joint synovial cyst treated with percutaneous steroid
      injections. At varying times after the procedure, patients were contacted for
      clinical follow-up, and repeat imaging was performed to verify the status of the
      cyst. RESULTS: Excellent pain relief was achieved in nine (75%) of 12 patients.
      At follow-up imaging, the cyst completely regressed in six (67%) of these nine
      patients, partially regressed in two (22%) patients, and was unchanged in one
      (11%) patient. One (8%) of the 12 patients had transient pain relief, with
      recurrence of symptoms at short intervals after each of three injections. No pain
      relief was achieved in two (17%) of 12 patients. CONCLUSION: Image-guided
      percutaneous steroid injections are often effective in the treatment of lumbar
      facet joint synovial cysts and may result in complete regression of the cyst.

PMID- 11568338
TI  - Anterolateral ankle impingement: mr arthrographic assessment of the anterolateral
      recess.
AB  - PURPOSE: To determine the accuracy of magnetic resonance (MR) arthrography in
      assessing the anterolateral recess of the ankle. MATERIALS AND METHODS: Thirty
      two patients with chronic ankle pain prospectively underwent gadolinium-enhanced
      MR arthrography of the tibiotalar joint. All underwent clinical examination and
      were included if anterolateral impingement (n = 13) or a control condition (n =
      19; suspected osteochondral defect, intraarticular bodies, instability,
      osteoarthritis) was diagnosed. MR imaging included transverse and coronal T1
      weighted and sagittal T2-weighted imaging sequences. Images were prospectively
      analyzed by two readers blinded to the clinical diagnosis. The anterolateral
      gutter contour was assessed. MR arthrographic findings were correlated with
      subsequent arthroscopic appearances. RESULTS: MR arthrographic assessment of the
      anterolateral soft tissues had an accuracy of 97%, sensitivity of 96%,
      specificity of 100%, negative predictive value of 89%, and positive predictive
      value of 100%. Accuracy was 100% with clinical anterolateral impingement, with an
      arthroscopically confirmed abnormality in 12 cases and a normal appearance in
      one. Anterolateral soft-tissue thickening was identified at MR arthrography in 11
      control cases, with arthroscopic confirmation in all. The remaining cases had
      normal appearances, with an arthroscopic soft-tissue abnormality in one case and
      a normal appearance in seven. CONCLUSION: MR arthrography of the tibiotalar joint
      is accurate in assessing the anterolateral recess of the ankle.

PMID- 11568339
TI  - MR imaging of the posterior cruciate ligament graft: initial experience in 15
      patients with clinical correlation.
AB  - PURPOSE: To describe the magnetic resonance (MR) appearance of the posterior
      cruciate ligament (PCL) graft in the 1st postoperative year and to correlate the
      MR findings with clinical examination findings. MATERIALS AND METHODS: Nineteen
      MR examinations were performed in 15 patients (with 15 grafts) 1-33 months after
      PCL reconstruction. Results of clinical follow-up were available in 14 patients.
      Graft shape and thickness were recorded, and intrasubstance signal intensity at
      T2-weighted imaging was graded. The MR findings were correlated with the time
      between surgery and clinical examination. RESULTS: At MR imaging, 13 grafts
      appeared intact, one could not be assessed owing to hardware artifact, and one
      initially appeared disrupted. Graft thickness was 7-19 mm. There was no
      significant difference between graft thickness versus time since surgery and
      signal intensity versus time since surgery (P =.14). In two of three patients who
      underwent sequential MR examinations, graft thickness and intrasubstance signal
      intensity decreased as the time between reconstruction and MR imaging increased.
      Two of 14 patients who underwent physical examination had a posterior drawer, and
      one also had an anterior cruciate ligament graft tear. Both patients with knee
      instability demonstrated intact PCL graft fibers at MR imaging. There was no
      correlation between knee stability and graft thickness, signal intensity, or
      shape. CONCLUSION: After PCL reconstruction, MR imaging in the 1st year depicts a
      thickened graft with increased signal intensity. There does not appear to be a
      relationship between clinical stability and findings at MR imaging.

PMID- 11568340
TI  - The blade of grass sign.

PMID- 11568341
TI  - Thymic lesions in patients with myasthenia gravis: characterization with thallium
      201 scintigraphy.
AB  - PURPOSE: To assess thallium 201 ((201)Tl) single photon emission computed
      tomography (SPECT) for evaluation of thymic lesions associated with myasthenia
      gravis (MG), including lymphoid follicular hyperplasia (LFH) and thymoma.
      MATERIALS AND METHODS: (201)Tl SPECT and computed tomography (CT) were performed
      preoperatively in 46 patients with MG who had undergone thymectomy. SPECT was
      conducted 15 (early image) and 180 (delayed image) minutes after (201)Tl
      injection. Results were visually assessed, and (201)Tl uptake ratios (thymic
      lesion count density/lung count density) were measured for quantitative analysis.
      Uptake was analyzed among the normal thymus, LFH, and thymoma patient groups.
      RESULTS: Histopathologic results indicated a normal thymus, LFH, and thymoma in
      19, 16, and 11 patients, respectively. Mean uptake ratios in the normal thymus,
      LFH, and thymoma were 0.96 (95% CI: 0.90, 1.03), 1.14 (95% CI: 1.04, 1.25), and
      1.87 (95% CI: 1.56, 2.25), respectively, on early images and 1.09 (95% CI: 1.00,
      1.18), 1.65 (95% CI: 1.48, 1.85), and 2.03 (95% CI: 1.65, 2.50), respectively, on
      delayed images. Thymoma showed more intense (201)Tl accumulation than did the
      normal thymus (P <.001) and LFH (P <.001) on early images. Both thymoma (P <.001)
      and LFH (P <.001) displayed more intense uptake than did the normal thymus on
      delayed images. CONCLUSION: (201)Tl SPECT can enable differentiation between
      normal thymus, LFH, and thymoma in patients with MG.

PMID- 11568342
TI  - Acute rejection following lung transplantation: limitations in accuracy of thin
      section CT for diagnosis.
AB  - PURPOSE: To evaluate the sensitivity, specificity, predictive values, and
      accuracy of thin-section computed tomography (CT) for the diagnosis of acute
      rejection following lung transplantation and to determine whether any individual
      CT abnormalities are associated with histopathologically proved acute rejection.
      MATERIALS AND METHODS: Thin-section CT studies from 64 lung transplant recipients
      were retrospectively reviewed. CT studies were temporally correlated with various
      grades of biopsy-proved acute rejection (n = 34); 30 other CT studies were from a
      control group with no histopathologic evidence of acute rejection. Acute
      rejection was diagnosed as present or absent, and the diagnostic was calculated.
      RESULTS: The sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy of CT for the diagnosis of acute rejection were as
      follows: 35%, 73%, 60%, 50%, 53%, respectively. No individual CT finding was
      significantly associated with acute rejection. The sensitivity of CT for the
      detection of various grades of acute rejection was 17% for grade A1, 50% for
      grade A2, and 20% for grade A3. The combination of volume loss and septal
      thickening, with or without pleural effusion, was never seen in the absence of
      acute rejection. CONCLUSION: Thin-section CT has limited accuracy for the
      diagnosis of acute rejection following lung transplantation, and no individual CT
      finding is significantly associated with this diagnosis.

PMID- 11568343
TI  - Spiral versus electron-beam CT for coronary artery calcium scoring.
AB  - PURPOSE: To determine differences in coronary artery calcium detection,
      quantification, and reproducibility, as measured at electron-beam computed
      tomography (CT) and subsecond spiral CT with retrospective electrocardiogram
      gating in an asymptomatic adult population. MATERIALS AND METHODS: Seventy
      subjects asymptomatic for coronary heart disease underwent both electron-beam CT
      and subsecond spiral CT. In all subjects, two images each were obtained with both
      scanners. Two experienced readers using three different algorithms scored each of
      the four scans: one score for the electron-beam CT images and two scores for the
      spiral CT images. RESULTS: With a 130-HU threshold for the quantification of
      calcium, there were no significant differences in interscan and interobserver
      variation in calcium scores between the electron-beam CT and spiral CT images.
      There was greater interobserver (P <.001) and interscan (P <.03) variation in
      scores when a 90-HU threshold was used for spiral CT images. With a 130-HU
      threshold, when calcium scores were used for clinical risk stratification, there
      was a significant difference between the results obtained with electron-beam CT
      and those obtained with spiral CT (P <.05). CONCLUSION: Spiral CT has not yet
      proved to be a feasible alternative to electron-beam CT for coronary artery
      calcium quantification. There are systematic differences between calcium scores
      obtained with single-detector array subsecond spiral CT and those obtained with
      electron-beam CT.

PMID- 11568344
TI  - Assessment of myocardial infarction in humans with (23)Na MR imaging: comparison
      with cine MR imaging and delayed contrast enhancement.
AB  - PURPOSE: To demonstrate the feasibility of sodium 23 ((23)Na) magnetic resonance
      (MR) imaging for assessment of subacute and chronic myocardial infarction and
      compare with cine, late enhancement, and T2-weighted imaging. MATERIALS AND
      METHODS: Thirty patients underwent MR imaging 8 days +/- 4 (subacute, n = 15) or
      more than 6 months (chronic, n = 15) after myocardial infarction by using a
      (23)Na surface coil with a double angulated electrocardiogram-triggered three
      dimensional gradient-echo sequence at 1.5 T. In addition, cine, inversion
      recovery gradient-echo, and, in the subacute group, T2-weighted images (n = 9)
      were obtained. Myocardial infarction mass was depicted as elevated signal
      intensity or wall motion abnormalities and expressed as a percentage of total
      left ventricular mass for all modalities. Correlations were tested with
      correlation coefficients. RESULTS: All patients after subacute infarction and 12
      of 15 patients with chronic infarction had an area of elevated (23)Na signal
      intensity that significantly correlated with wall motion abnormalities (subacute;
      r = 0.96, P <.001, and chronic; r = 0.9, P <.001); three patients had no wall
      motion abnormalities or elevated (23)Na signal intensity. Only 10 patients in the
      subacute and nine in the chronic group revealed late enhancement; significant
      correlation with (23)Na MR imaging occurred only in subacute group (r = 0.68, P
      <.05). Myocardial edema in subacute infarction correlated (r = 0.71, P <.05) with
      areas of elevated (23)Na signal intensity but was extensively larger. CONCLUSION:
      (23)Na MR imaging demonstrates dysfunctional myocardium caused by subacute and
      chronic myocardial infarction.

PMID- 11568345
TI  - Coronary microvascular functional reserve: quantification of long-term changes
      with electron-beam CT preliminary results in a porcine model.
AB  - PURPOSE: To evaluate the ability of electron-beam computed tomography (CT) to
      help quantify long-term changes in coronary microvascular functional reserve in a
      porcine model. MATERIALS AND METHODS: Electron-beam CT-based intramyocardial
      blood volume and perfusion and Doppler ultrasonography (US)-based intracoronary
      blood flow were obtained in 13 pigs at baseline and again 3 months later.
      Measurements were obtained at rest and after the administration of adenosine. The
      short-term variation during 30 minutes of electron-beam CT measurements was
      assessed in nine additional pigs. RESULTS: Short-term variation of blood volume
      and perfusion averaged 8% and 9%, respectively, and was similar for both weight
      groups at rest and after adenosine administration. At rest, intracoronary blood
      flow, blood volume, and perfusion remained unchanged from baseline to follow-up.
      Long-term increases (percentage change with adenosine relative to that at rest)
      in blood volume and perfusion reserves were consistent with increasing
      intracoronary blood flow reserves. Despite these long-term changes in
      intracoronary blood flow, blood volume, and perfusion, the blood volume-to
      perfusion relationship suggests a similar blood volume distribution among
      different microvascular functional components in normal porcine myocardium at
      both weight groups. CONCLUSION: Electron-beam CT may be of value for quantifying
      long-term changes in intramyocardial microvascular function.

PMID- 11568346
TI  - USPIO-enhanced direct MR imaging of thrombus: preclinical evaluation in rabbits.
AB  - PURPOSE: To test the hypothesis that ultrasmall superparamagnetic iron oxide
      (USPIO) particles may diffuse into nonendothelialized fresh thrombi and thus
      allow for direct magnetic resonance (MR) imaging of a thrombus. MATERIALS AND
      METHODS: Stagnation thrombi of different thrombus ages (1, 3, 5, 7, and 9 days)
      were induced in the external jugular veins of 25 rabbits. Direct MR imaging of
      thrombi was performed by using a fat-saturated T1-weighted gradient-echo sequence
      (three-dimensional [3D] magnetization prepared rapid acquisition gradient echo)
      before and 24 hours after intravenous administration of USPIO (particle size, 25
      nm; 200 micromol per kilogram of body weight). Thrombus length on 3D
      reconstruction images was compared with that depicted on a radiographic venogram
      and with histologic findings (joint reference standard). In addition, T2*
      weighted gradient-echo images were acquired and scored semiquantitatively.
      RESULTS: The hyperintensity of the thrombus segment depicted on T1-weighted
      images (thrombus length determined with 3D reconstruction images divided by true
      thrombus length) increased significantly after administration of contrast medium
      at a thrombus age of 3 days (0.6 +/- 0.4 [SD] to 0.8 +/- 0.4; P =.02), 5 days
      (0.1 +/- 0.1 to 1.0 +/- 0.1; P <.001), and 7 days (0 to 0.6 +/- 0.4; P =.02), but
      not at an age of 1 and 9 days. No significant change in the thrombus signal
      intensity was observed on T2*-weighted images. CONCLUSION: The animal model
      showed that direct MR imaging of the thrombus improved 24 hours after USPIO
      administration with a T1-weighted sequence. No improvement was seen with the T2*
      weighted sequence.

PMID- 11568347
TI  - Human transferrin receptor gene as a marker gene for MR imaging.
AB  - PURPOSE: To quantitate and characterize the expression of an engineered human
      transferrin receptor (ETR) as a marker gene by using magnetic resonance (MR)
      imaging. MATERIALS AND METHODS: Rat gliosarcoma 9L cells stably expressing ETR
      (ETR+) were used, with nontransfected (ETR-) cells serving as controls. A
      conjugate of transferrin and monocrystalline iron oxide (Tf-MION) nanoparticles
      was synthesized to probe for the activity of ETR. Accumulation of Tf-MION was
      examined by using cell internalization in culture and MR (n = 6) and nuclear (n =
      4) imaging in a mouse model with ETR+ and ETR- tumors implanted in the opposite
      flanks. Autoradiographic and histopathologic results were correlated with MR
      findings. RESULTS: Tf-MION was internalized by ETR+ cells at 37 degrees C but not
      at 4 degrees C. Rhodamine-labeled Tf-MION and fluorescein-labeled antibody to ETR
      colocalized in small vesicle-like structures in the cytoplasm. Both findings were
      consistent with accumulation by the receptor-mediated endocytosis mechanism of
      ETR. Compared with ETR- tumors, ETR+ tumors accumulated more Tf-MION and had
      higher signal intensity on T1-weighted MR images and lower signal intensity on T2
      weighted images. Autoradiographic findings showed a spatial correlation between
      MR signal intensity and TF-MION accumulation. CONCLUSION: ETR+ tumors internalize
      the MR imaging probe through the action of transferrin receptor in amounts that
      can be detected with MR imaging.

PMID- 11568348
TI  - Suppression of cerebrospinal fluid and blood flow artifacts in FLAIR MR imaging
      with a single-slab three-dimensional pulse sequence: initial experience.
AB  - The authors compared high-signal-intensity flow-related artifacts present with a
      conventional two-dimensional (2D) fluid-attenuated inversion recovery (FLAIR)
      sequence with those seen with a single-slab, three-dimensional (3D) FLAIR
      sequence. Four readers graded the subarachnoid space and intraventricular
      artifacts, the pulsation artifacts, and the conspicuity of cranial nerves in the
      posterior fossa. For all comparisons, differences between 2D and 3D images were
      highly statistically significant, with 3D imaging being superior in all cases.

PMID- 11568349
TI  - Painful multifocal arthritis: therapy with rhenium 186
      hydroxyethylidenediphosphonate ((186)Re HEDP) after failed treatment with
      medication--initial results of a prospective study.
AB  - Eight patients (77 joints) with polyarthritis were treated systemically with 570
      MBq (15.4 mCi) of rhenium 186 ((186)Re) hydroxyethylidenediphosphonate (HEDP).
      Pain and disease activity were assessed monthly. In six (75%) of eight patients,
      a single injection of (186)Re HEDP led to an improvement in disease activity.
      Systemic low-dose treatment with (186)Re HEDP can reduce pain and disease
      activity in patients with polyarthritis.

PMID- 11568350
TI  - Unilateral renal artery stenosis: perfusion patterns with electron-beam dynamic
      CT--preliminary experience.
AB  - Renal dynamic computed tomographic (CT) data for 16 patients with unilateral
      renal artery stenosis were compared with those for 12 control subjects. Three
      patterns of perfusion were distinguished in stenotic kidneys: pattern A,
      symmetric time-attenuation curves; pattern B, asymmetric time-attenuation curve
      with similar perfusion; and pattern C, asymmetric time-attenuation curve with
      impaired perfusion. Additional functional data can be obtained from the initial
      timing scan in a CT study of unilateral renal artery stenosis.

PMID- 11568351
TI  - Aorta and runoff vessels: single-injection MR angiography with automated table
      movement compared with multiinjection time-resolved MR angiography--initial
      results.
AB  - The authors compared two techniques for performing runoff, contrast material
      enhanced magnetic resonance (MR) angiography. Multiinjection time-resolved
      imaging of contrast kinetics (TRICKS) and single-injection bolus-chase MR
      angiographic examinations were performed in 10 volunteers and 10 patients. Image
      quality and venous overlay of the major blood vessels of the abdomen, thigh, and
      calf were evaluated. Significantly more (P <.05) vessels were depicted with
      diagnostic quality on multiinjection TRICKS than on single-injection bolus-chase
      MR angiographic images.

PMID- 11568352
TI  - The double-contrast barium enema examination.

PMID- 11568353
TI  - Double-imaging mammography.

PMID- 11568354
TI  - Routine opposed-phase flash MR imaging does not quantify fat content.

PMID- 11568356
TI  - Louis James Casarett (1927-1972).

PMID- 11568357
TI  - Genetically modified plants and human health risks: Can additional research
      reduce uncertainties and increase public confidence?
AB  - So long as the risks to human health from transgenic plants remain potential
      rather than actual, and, in any event, appear lower than those from traditional
      plant breeding, hazard assessment need not be extensive. However, in view of
      current public attitudes to transgenic plants, it is necessary that those tests
      that are required, be based on logic, on sound science, and in accordance with
      the best scientific methodology. This is particularly the case with testing for
      food allergenicity. Current testing is largely indirect and based on comparisons
      with other known food allergens. Development of direct tests that involve
      interaction between the actual transgenic protein in question and the immune
      system is essential if confidence in the regulatory system is to be restored.

PMID- 11568358
TI  - Elimination of cocaine by pregnant sheep following single or multiple exposures.
AB  - To test the hypothesis that chronic exposure to cocaine would alter drug
      elimination in pregnant and fetal sheep compared to a single exposure, we
      administered intravenous cocaine HCl to 8 pregnant sheep daily as a bolus,
      followed by a 2-h infusion beginning at gestational age 75 days. Eight additional
      animals received an equivalent volume of saline. Three days after maternal and
      fetal catheter placement on day 125, ewes in both groups received cocaine HCl, 2
      mg/kg, as a bolus. Maternal and fetal plasma samples were serially obtained and
      analyzed for cocaine and benzoylecognine. Cocaine half-life in the ewes and
      fetuses exposed to cocaine was no different from that in animals exposed to
      saline. We conclude that cocaine is rapidly metabolized in pregnant sheep and
      that chronic administration does not alter drug clearance.

PMID- 11568359
TI  - Development of a physiologically based pharmacokinetic model of isopropanol and
      its metabolite acetone.
AB  - A physiologically based pharmacokinetic (PBPK) model for isopropanol (IPA) and
      its major metabolite, acetone, is described. The structure of the parent chemical
      model, which can be used for either IPA or acetone by choosing the appropriate
      chemical-specific parameters, is similar to previously published models of
      volatile organic chemicals such as styrene. However, in order to properly
      simulate data on the exhalation of IPA and acetone during inhalation exposures,
      it was necessary to expand the description of the lung compartment to include a
      subcompartment for the upper respiratory tract mucus layer. This elaboration is
      consistent with published PBPK models of other water-soluble vapors in which the
      mucus layer serves to absorb the chemical during inhalation and then release it
      during exhalation. In the case of IPA exposure, a similar PBPK structure is used
      to describe the kinetics of the acetone produced from the metabolism of IPA. The
      resulting model is able to provide a coherent description of IPA and acetone
      kinetics in the rat and human for exposures to IPA by several routes:
      intravenous, intraperitoneal, oral, inhalation, and dermal. It is also able to
      consistently reproduce kinetic data for exposures of rats or humans to acetone.
      Thus, the model provides a validated framework for performing chemical-specific
      route-to-route extrapolation and cross-species dosimetry, which can be used in
      place of generic default calculations in support of risk assessments for IPA and
      acetone.

PMID- 11568360
TI  - Effects of beta-estradiol and bisphenol A on heat shock protein levels and
      localization in the mouse uterus are antagonized by the antiestrogen ICI 182,780.
AB  - Bisphenol A (BPA) exhibits many estrogen-like effects in the rodent uterus, but
      not all of these can be attenuated by antiestrogens. This suggests the
      involvement of alternate pathways of BPA action that do not involve the estrogen
      receptor (ER). An examination of the in vivo effects of BPA on uterine gene
      expression and protein levels should contribute to an understanding of its
      mechanism of action. In this study we examined the dose-related effects of BPA on
      levels of a suite of heat shock proteins (hsps) and on the localization of
      hsp90alpha, a chaperone of the ER, in uteri of ovariectomized B6C3F1 mice and
      compared these effects with those of beta-estradiol (E2). The antiestrogen ICI
      182,780 (ICI) was co-administered with BPA or E2 in order to examine the
      potential role of the ER. BPA, although less potent than E2, increased hsp90alpha
      and grp94 to similar levels, but was much less effective than E2 in increasing
      levels of hsp72. Treatment with 100 mg BPA/kg/day or 2 microg E2/kg/day increased
      hsp90alpha to 300% of control levels and altered its tissue expression pattern.
      In uteri of corn oil (control)-treated mice, hsp90alpha predominantly localized
      in the cytoplasm and nuclei of epithelial cells. Upon treatment with BPA or E2
      there was increased intensity of staining in the stroma and myometrium, and in
      the epithelium hsp90alpha was localized almost exclusively in the cytoplasm. The
      effects of BPA or E2 on hsp levels and hsp90alpha localization were attenuated by
      ICI. These results suggest an involvement of the ER in BPA- and E2-induced
      increases in uterine levels of hsp90alpha, grp94, and hsp72, and localization of
      hsp90alpha.

PMID- 11568361
TI  - The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on corticotrophin-releasing
      hormone, arginine vasopressin, and pro-opiomelanocortin mRNA levels in the
      hypothalamus of the cynomolgus monkey.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental
      contaminant that has profound deleterious effects on development and
      reproduction. TCDD may act at one or more levels to alter the hypothalamic
      pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. The
      objective of this study was to investigate whether TCDD modulates neuroendocrine
      systems by altering gene expression of arginine vasopressin (AVP), corticotrophin
      releasing hormone (CRH), or pro-opiomelanocortin (POMC), which are important
      neuroregulators of the HPA and HPG axes. Four groups of female cynomolgus monkeys
      (Macaca fascicularis) were administered daily oral doses of gelatin capsule
      containing TCDD (0, 1, 5, or 25 ng/kg body weight) mixed with glucose 5 days a
      week for 1 year. At the end of the dosing period, animals were euthanized and
      brains were harvested. CRH, AVP, and POMC mRNA levels were semiquantified by in
      situ hybridization histochemistry on 30-microm coronal sections of the brain.
      Blood collected on the day of euthanasia was assayed for cortisol and
      progesterone. CRH mRNA levels in the paraventricular nucleus (PVN) were
      significantly increased by the 2 higher TCDD doses (5 and 25 ng/kg/day) compared
      to controls (p < 0.05). There was a trend towards increased AVP mRNA levels in
      both the supraoptic nucleus (SON) and PVN. No effect of TCDD on POMC was
      observed. Cortisol levels were significantly increased in TCDD-exposed animals.
      Progesterone concentrations and menstruation data indicated that TCDD did not
      interfere with ovulation. We conclude that TCDD stimulated the HPA axis by a
      central effect involving CRH, but had no effect on the HPG axis at the doses
      tested.

PMID- 11568362
TI  - Mechanisms of arsenic-induced cross-tolerance to nickel cytotoxicity,
      genotoxicity, and apoptosis in rat liver epithelial cells.
AB  - The purpose of the present study was to investigate the mechanism of cross
      tolerance to nickel in arsenic-transformed cells. Chronic arsenite-exposed (CAsE)
      cells (TRL 1215 cells, which had been continuously exposed to 0.5 microM arsenite
      for 20 or more weeks) and control TRL 1215 cells were both exposed to nickel for
      24 h, and cell viability was determined by metabolic integrity. The LC(50) for
      nickel was 608 +/- 32 microM in CAsE cells as compared to 232 +/- 16 microM in
      control cells, a 2.6-fold increase. CAsE and control cells were treated with 200
      microM nickel for 4 h and cellular-free radical production was measured using ESR
      spectrometry. Hydroxyl radical generation was decreased in CAsE cells.
      Thiobarbituric acid reactive substances, indicative of lipid peroxidation, and 8
      oxo-2'-deoxyguanosine, indicative of oxidative DNA damage, were reduced in CAsE
      cells. Flow cytometric analysis using Annexin/FITC revealed that nickel-induced
      apoptosis was reduced in CAsE cells. CAsE cells showed generalized resistance to
      oxidant-induced toxicity as evidenced by a marked reduction in sensitivity to
      hydrogen peroxide. Interestingly, intracellular reduced glutathione (GSH) levels
      were significantly increased in CAsE cells, and when GSH was depleted, CAsE cells
      lost their nickel resistance. The mechanism of arsenic-induced cross-tolerance to
      cytotoxicity, genotoxicity, and apoptosis induced by nickel appears related to a
      generalized resistance to oxidant-induced injury, probably based, at least in
      part, in increased cellular GSH levels.

PMID- 11568363
TI  - Assessment of cisplatin-induced nephrotoxicity by microarray technology.
AB  - Microarrays are a new technology used to study global gene expression and to
      decipher biological pathways. In the current study, microarrays were used to
      examine gene expression patterns associated with cisplatin-mediated
      nephrotoxicity. Sprague-Dawley rats received either single or seven daily ip
      doses of cisplatin (0.5 or 1 mg/kg/day) or the inactive isomer transplatin (1 or
      3 mg/kg/day). Histopathological evaluation revealed renal proximal tubular
      necrosis in animals that received cisplatin for 7 days, but no hepatotoxic
      findings. Microarray analyses were performed using rat specific arrays containing
      250 toxicity-related genes. Prominent gene expression changes were observed only
      in the kidneys of rats that received cisplatin for 7 days. Mechanistically, the
      gene expression pattern elicited by cisplatin (e.g., Bax upward arrow and SMP-30
      downward arrow) suggested the occurrence of apoptosis and the perturbation of
      intracellular calcium homeostasis. The induction of multidrug resistance genes
      (MDR1 upward arrow, P-gp upward arrow) and tissue remodeling proteins (clusterin
      upward arrow, IGFBP-1 upward arrow, and TIMP-1 upward arrow) indicated the
      development of cisplatin resistance and tissue regeneration. Select gene
      expression changes were further confirmed by TaqMan analyses. Gene expression
      changes were not observed in the liver following cisplatin administration. In
      contrast to these in vivo findings, studies using NRK-52E kidney epithelial cells
      and clone-9 liver cells suggested that liver cells were more sensitive to
      cisplatin treatment. The discrepancies between the in vivo and in vitro results
      suggest that caution should be taken when extrapolating data from in vivo to in
      vitro systems. Nonetheless, the current study elucidates the biochemical pathways
      involved in cisplatin toxicity and demonstrates the utility of microarrays in
      toxicological studies.

PMID- 11568364
TI  - Interactions of rat brain acetylcholinesterase with the detergent Triton X-100
      and the organophosphate paraoxon.
AB  - Inhibition of the critical enzyme acetylcholinesterase (E.C. 3.1.1.7) with
      subsequent cholinergic crisis is the mechanism of acute toxicity of the
      organophosphorus insecticides (B. E. Mileson et al., 1998, Toxicol. Sci.41, 8
      20). Consequently, measurement of acetylcholinesterase activity is important for
      evaluating the mammalian toxicity of this commonly used class of insecticides.
      While mammalian acetylcholinesterase activity has often been determined in tissue
      homogenates in the presence of the nondenaturing detergent Triton X-100 at a
      concentration of 1%, the potential actions of this detergent on the activity of
      this critical enzyme are not understood. In the current study, homogenization of
      rat brain in buffer containing 1% Triton X-100 slightly elevated the (app)V(max)
      for hydrolysis of acetylthiocholine, without affecting the (app)K(m) or the
      (app)K(ss). However, the presence of both 1% Triton X-100 and paraoxon (at
      concentrations of 5 nM-100 nM) resulted in complex kinetic interactions with
      acetylcholinesterase, as evidenced by a curvilinear secondary plot for
      determination of the (app)k(i). These results suggest that measurement of
      acetylcholinesterase activity in the presence of up to 1% Triton X-100, but in
      the absence of oxon, should pose no problems with regard to data interpretation,
      provided it is recognized that the detergent slightly elevates activity. However,
      measurement of acetylcholinesterase activity after enzyme was exposed
      simultaneously to Triton X-100 and oxon could be problematic. Caution is
      warranted when interpreting data where acetylcholinesterase activity was
      determined under such conditions since in the presence of 1% Triton X-100, the
      capacity of oxon to inhibit acetylcholinesterase might change as a function of
      oxon levels.

PMID- 11568365
TI  - p53-dependent induction of p21(Cip1/WAF1/Sdi1) protects against oxygen-induced
      toxicity.
AB  - The beneficial effects of supplemental oxygen delivered to patients suffering
      from acute respiratory distress is offset by its reduction to genotoxic reactive
      oxygen species (ROS) that inhibit proliferation and kill pulmonary cells. Cells
      respond to oxygen-induced damage by expressing the tumor suppressor p53 and the
      cyclin-dependent kinase inhibitor p21(Cip1/WAF1/Sdi1) (p21), which limits
      proliferation by blocking entry into S phase. Since preventing DNA synthesis
      during genotoxic stress may enhance survival, the current study examines whether
      hyperoxia induces p21 through a p53-dependent pathway and whether p21 protects
      cells from the toxic effects of oxygen. HCT116 colon carcinoma cells and clonal
      lines lacking p53 or p21were used in this study because they allow direct
      cytotoxic comparisons between isogenic cells, without complications arising from
      unknown genetic differences between nonhomologous cell lines. Hyperoxia (95% O2,
      5% CO2) increased p53 abundance, phosphorylation of p53 on serine 15, and p21
      mRNA and protein in parental HCT116 cells that ceased proliferation. In contrast,
      p21 was not detected in either p53- or p21-deficient HCT116 cells, which exited
      the G1 compartment and were arrested in S and G2/M phases during hyperoxia.
      Trypan blue-dye exclusion revealed that induction of p21 markedly enhanced
      survival during exposure and colony survival assays showed that p21 enhanced the
      ability to resume proliferation during recovery in room air. The observation that
      p53-dependent induction of p21 prevents exit from G1 and promotes survival during
      hyperoxia is consistent with the importance of limiting DNA replication during
      genotoxic stress caused by oxygen exposure.

PMID- 11568366
TI  - Prediction of organophosphorus acetylcholinesterase inhibition using three
      dimensional quantitative structure-activity relationship (3D-QSAR) methods.
AB  - Neurotoxic organophosphorous compounds are known to modulate their biological
      effects through the inhibition of a number of esterases including
      acetylcholinesterase (AChE), the enzyme responsible for the degradation of the
      neurotransmitter acetylcholine. In this light, molecular modeling studies were
      performed on a collection of organophosphorous acetylcholinesterase inhibitors by
      the combined use of conformational analysis and 3D-QSAR methods to rationalize
      their inhibitory potencies against the enzyme. The Catalyst program was used to
      identify the structural features in the group of 8 inhibitors whose IC(50) values
      ranged from 0.34 nM to 1.2 microM. The 3-D pharmacophore models are characterized
      by at least one hydrogen bond acceptor site and 2-3 hydrophobic sites and
      demonstrate very good correlation between the predicted and experimental IC(50)
      values. Our models can be useful in screening databases of organophosphorous
      compounds for their neurotoxicity potential via the inhibition of
      acetylcholinesterase. Also, the pharmacophores offer an additional means of
      designing AChE inhibitors as potential therapeutic agents for central nervous
      system diseases.

PMID- 11568367
TI  - Ocular and nasal trigeminal detection of butyl acetate and toluene presented
      singly and in mixtures.
AB  - To probe into the rules of trigeminal chemosensory agonism in a binary mixture of
      chemicals we measured, first, the detectability (i.e., psychometric) function for
      eye irritation and for nasal pungency of butyl acetate and toluene, singly. (To
      avoid olfactory biases, nasal pungency was measured in a group of anosmics, i.e.,
      persons lacking a functional sense of smell.) Then, based on the detectability
      function obtained for the individual chemicals, we prepared mixtures where the 2
      components varied in their relative proportions but, if a simple rule of complete
      sensory agonism (in the sense of dose-additivity) were to hold, the mixtures
      should be as detectable as the reference concentration of each of the single
      chemicals. For both trigeminal endpoints (i.e., eye irritation and nasal
      pungency), the results showed that stimuli of relatively low detectability did
      show complete sensory agonism, whereas stimuli of relatively high detectability
      fell short of complete sensory agonism when compared with the detectability of
      the single substances. Further testing of additional binary and higher order
      mixtures will confirm whether or not a structure-activity model of trigeminal
      chemosensory impact of single chemicals, based on selected physicochemical
      parameters of the stimuli, can also be applied to chemical mixtures.

PMID- 11568368
TI  - Beneficial effects of NTP-2000 diet on growth, survival, and kidney and heart
      diseases of Fischer 344 rats in chronic studies.
AB  - Diet is one of the most important environmental factors influencing growth,
      survival, and appearance of age-associated diseases in rodents. NIH-07 open
      formula rodent diet was the selected diet for the National Toxicology Program
      studies from 1980 to 1994. After a number of experimental diets were evaluated, a
      new one designated as NTP-2000 was selected for rodents in NTP studies beginning
      in 1994. This report summarizes the results of dosed feed and inhalation studies
      for differences in growth, survival, and severity of kidney and heart lesions in
      Fischer 344 rats fed NTP-2000 or NIH-07 diets. In the dosed feed studies, male
      rats group housed and fed the NTP-2000 diet grew slightly slower, attained
      maximum body weight later, and lost less body weight by the end of the 2-year
      studies compared to the groups fed NIH-07. Female rats group housed and fed the
      NTP-2000 diet in dosed feed studies had significantly slower growth, with lower
      maximum body weight compared to the groups fed the NIH-07 diet. In the inhalation
      studies, male rats individually housed and fed the NTP-2000 diet had slightly
      higher maximum body weight and significantly higher final body weight, with lower
      loss of weight when compared to similarly housed groups fed the NIH-07 diet. In
      inhalation studies, female rats fed the NTP-2000 diet and individually housed had
      significantly slower growth. The NTP-2000 diet significantly increased the
      survival of male and female rats, with a dramatic increase in survival of males
      in inhalation studies. This diet also caused significant decreases in severity of
      nephropathy and cardiomyopathy, and the decrease was marked in males. These
      observations indicate that diets balanced for nutrients, such as the NTP-2000,
      could markedly improve the health and increase survival of the rats used in
      chronic studies.

PMID- 11568369
TI  - Species-, sex-, and cell type-specific effects of ochratoxin A and B.
AB  - The ubiquitous mycotoxin ochratoxin A (OTA) is associated with the development of
      urothelial tumors and nephropathies in laboratory animals and in humans with
      stark species and sex differences with respect to susceptibility in disease
      development. The mechanism of action remains unknown. OTA-mediated disruptions in
      normal cell-cycle control could be a major constituent of the mechanisms
      underlying both its carcinogenic and nephropathy-inducing activities. Assessment
      of OTA's toxic effects (sum of antiproliferative, apoptotic, and necrotic
      effects) in rat and porcine continuous cell lines and in primary cells from
      humans and pigs of both sexes, have displayed a similar sex- and species
      sensitivity rank order to that observed in previous in vivo experiments.
      Furthermore, these toxic effects were observed at nM concentrations in the
      presence of serum in vitro, thus closely mimicking the in vivo situation. These
      effects were reversible in all cell types except in human primary epithelial
      cells of both sexes and did not appear to be primarily dependent on the amount of
      OTA taken up. Indeed, fibroblasts (NRK-49F) were insensitive to OTA-mediated cell
      cycle inhibition in spite of accumulating comparable amounts of OTA. The results
      presented here support the continued use of primary renal epithelial cells for
      the investigation of the mechanism of OTA-induced carcinogenesis and nephropathy
      and provide an as-yet preliminary data set that supports the existence of a
      causal relationship between OTA exposure and human nephropathy.

PMID- 11568370
TI  - Environment and child health: what is Stachybotrys?

PMID- 11568371
TI  - Burden of morbidities and the unmet need for health care in rural neonates--a
      prospective observational study in Gadchiroli, India.
AB  - BACKGROUND: Majority of the neonates in developing countries are born and cared
      for in rural homes but the available information is mostly hospital based.
      OBJECTIVES: To estimate: (i) the incidence of various neonatal morbidities and
      associated case fatality in home-cared rural neonates, (ii) proportion of
      neonates with indications for health care, and (iii) the proportion who actually
      receive it. DESIGN: Prospective observational study. SETTING: Rural homes.
      METHODS: Neonates in 39 study villages in the Gadchiroli district (Maharashtra,
      India) were observed during one year (1995-96) by 39 trained female village
      health workers at birth and during neonatal period (0-28 days) by making eight
      home visits. A physician checked the data and the morbidities were diagnosed by a
      computer program. Vital statistics in these villages was independently collected.
      RESULTS: Out of 1016 live births, 95% occurred at home and 763 (75&%) neonates
      were observed. The agreement between observations by health workers and physician
      was 92%. Total 48.2& neonates suffered high risk morbidities (associated case
      fatality >10%), 72.2% suffered low risk morbidities, and 17.9% gained inadequate
      weight (less than 300 g). Seventeen percent neonates developed clinical picture
      suggestive of sepsis. Though 54.4% neonates had indications for health care and
      38 out of total 40 neonatal deaths occurred in these, only 2.6% received medical
      attention. The neonatal mortality rate was 52.4/1000 live births. CONCLUSION:
      Nearly half of the neonates in rural homes developed high risk morbidities ten
      times the neonatal morbidity rate and needed health care but practically none
      received it. The magnitude of care gap suggests an urgent need for developing
      home-based neonatal care to reduce neonatal morbidities and mortality

PMID- 11568372
TI  - Midazolam sedation in mechanically ventilated newborns: a double blind randomized
      placebo controlled trial.
AB  - OBJECTIVE: To determine efficacy of midazolam as a sedative in mechanically
      ventilated newborns. DESIGN: Double blind randomized placebo controlled trial.
      SETTING: Neonatal Unit of Tertiary Hospital. OUTCOME: Sedation over 48 h of
      observation. METHODS: Neonates with birth weight less than 2000 g who were
      mechanically ventilated within 7 days of life were randomly assigned to midazolam
      and placebo group. Midazolam and placebo were administered as bolus (0.2 mg/kg)
      followed by continuous infusion (0.06 mg/kg/h). Both groups received morphine
      infusion (10 microg/kg/h). Sedation score was noted at 6 hourly intervals for 48
      hours. Hemodynamic variables, ventilatory variables, complications and side
      effects of treatments were also recorded. RESULTS: Thirty-three neonates were
      enrolled (17 in midazolam, 16 in placebo group). The groups were comparable for
      birth weights and gestation. The midazolam group had significantly better
      sedation from 18-24 hours after enrollment compared to placebo group. At 48 h
      there were no significant differences in proportion of infants with adequate
      sedation between midazolam and placebo group. The two groups were comparable with
      respect to heart rate, perfusion, ventilatory indices and blood gas parameters.
      None of the infants were noted to have hypotension on loading with midazolam or
      placebo. Seizures were noted in 2 neonates in placebo group 24 hours after
      enrollment (insignificant statistically). CONCLUSION: Sedation provided by
      continuous infusion of midazolam and morphine appears to be comparable to
      morphine alone in newborn babies on mechanical ventilation, with no significant
      adverse effects. The course of mechanical ventilation is not influenced by use of
      midazolam.

PMID- 11568373
TI  - Consensus statement on management of steroid sensitive nephrotic syndrome.

PMID- 11568374
TI  - The art and science of conducting a continuing medical education program.

PMID- 11568375
TI  - Three common dermatological disorders in children (scabies, pediculosis and
      dermatophytoses).

PMID- 11568376
TI  - A comprehensive study of morbidity in school age children.

PMID- 11568377
TI  - Physical activity and pregnancy outcome in rural undernourished women.

PMID- 11568378
TI  - Verbal autopsy determined causes of neonatal deaths.

PMID- 11568379
TI  - Serum nitrite and urinary nitrite excretion in nephrotic syndrome.

PMID- 11568380
TI  - Hyperimmunoglobulin E syndrome.

PMID- 11568381
TI  - Non-Wilsonian cirrhosis in Turkish children.

PMID- 11568382
TI  - Surfactant protein B deficiency: a rare but lethal condition in newborn.

PMID- 11568383
TI  - Sirenomelia sequence associated with craniorachischisis totalis, limb reduction
      and primitive heart.

PMID- 11568385
TI  - Schizencephaly type-I.

PMID- 11568384
TI  - Joubert syndrome.

PMID- 11568386
TI  - Neonatal hepatic hemagioendothelioma: unusual presentations.

PMID- 11568387
TI  - Dopa-responsive dystonia.

PMID- 11568388
TI  - Infantile pustular psoriasis--may mimic seborrhic dermatitis.

PMID- 11568389
TI  - Dyscephalia mandibulo-oculo-facialis.

PMID- 11568390
TI  - A novel growth assessment chart for adolescents.

PMID- 11568391
TI  - Throat clearing habit and ascariasis.

PMID- 11568392
TI  - Autism: some conceptual issues.

PMID- 11568394
TI  - Medical negligence and vaccine associated paralytic poliomyelitis.

PMID- 11568396
TI  - Split cord malformations.

PMID- 11568397
TI  - Sialic acid levels in healthy preterm and full term infants.

PMID- 11568398
TI  - An exploratory study of the relationship between face recognition memory and the
      volume of medial temporal lobe structures in healthy young males.
AB  - A rigorous new methodology was applied to the study of structure function
      relationships in the living human brain. Face recognition memory (FRM) and other
      cognitive measures were made in 29 healthy young male subjects (mean age = 21.7
      years) and related to volumetric measurements of their cerebral hemispheres and
      of structures in their medial temporal lobes, obtained using the Cavalieri method
      in combination with high resolution Magnetic Resonance Imaging (MRI. Greatest
      proportional variability in volumes was found for the lateral ventricles (57%)
      for the cerebral hemispheres (8%) in the mean volumes of the hippocampus,
      parahippocampal gyrus, amygdala, caudate nucleus, temporal pole and temporal lobe
      on the right and left sides of the brain. The volumes of the right and left
      parahippocampal gyrus, temporal pole, temporal lobe, and left hippocampus were,
      prior to application of the Bonferroni correction to take account of 12 multiple
      comparisons, significantly correlated with the volume of the corresponding
      hemisphere(p < 0.05). The volumes of all structures were highly correlated (p <
      0.0002 for all comparisons) between the two cerebral hemispheres. There were no
      positive relationships between structure volumes and FRM score. However, the
      volume of the right amygdala was, prior to application of the Bonferroni
      correction to take account of 38~multiple comparisons, found to be significantly
      smaller in the five most consistent high scorers compared to the five most
      consistent low scorers (t = 2.77,p = 0.025). The implications for possible
      relationships between healthy medial temporal lobe structures and memory are
      discussed.

PMID- 11568399
TI  - Electric source localization adds evidence for task-specific CNVs.
AB  - This study was an attempt to replicate recent magnetoencephalographic (MEG)
      findings on human task-specific CNV sources (Basile et al.,
      Electroencephalography and Clinical Neurophysiology 90, 1994, 157-165) by means
      of a spatio-temporal electric source localization method (Scherg and von Cramon,
      Electroencephalography and Clinical Neurophysiology 62, 1985, 32-44; Scherg and
      von Cramon, Electroencephalography and Clinical Neurophysiology 65, 1986, 344
      360; Scherg and Berg, Brain Electric Source Analysis Handbook, Version 2). The
      previous MEG results showed CNV sources in the prefrontal cortex of the two
      hemispheres for two tasks used, namely visual pattern recognition and visual
      spatial recognition tasks. In the right hemisphere, the sources were more
      anterior and inferior for the spatial recognition task than for the pattern
      recognition task. In the present study we obtained CNVs in five subjects during
      two tasks identical to the MEG study. The elicited electric potentials were
      modeled with four spatio-temporal dipoles for each task, three of which accounted
      for the visual evoked response and one that accounted for the CNV. For all
      subjects the dipole explaining the CNV was always localized in the frontal region
      of the head, however, the dipole obtained during the visual spatial recognition
      task was more anterior than the one obtained during the pattern recognition task.
      Thus, task-specific CNV sources were again observed, although the stable model
      consisted of only one dipole located close to the midline instead of one dipole
      in each hemisphere. This was a major difference in the CNV sources between the
      previous MEG and the present electric source analysis results. We discuss the
      possible basis for the difference between the two methods used to study slow
      brain activity that is believed to originate from extended cortical patches.

PMID- 11568400
TI  - Emotional processing following cortical and subcortical brain damage:
      contribution of the fronto-striatal circuitry.
AB  - The present study examined the differential contribution of cortical and
      subcortical brain structures in emotional processing by comparing patients with
      focal cortical lesions (n = 32) to those with primarily subcortical dysregulation
      of the basal ganglia (Parkinson's disease n = 14). A standardized measure of
      emotional perception (Tubingen Affect Battery) was used. Only patients in the
      more advanced stages of Parkinson's disease and patients with focal damage to the
      (right) frontal lobe differed significantly from controls in both facial
      expression and affective prosody recognition. The findings imply involvement of
      the fronto-striatal circuitry in emotional processing.

PMID- 11568401
TI  - 'Pure' constructional apraxia - a cognitive analysis of a single case.
AB  - We report on a patient affected by selective drawing disabilities. The patient
      could correctly reproduce and draw simple geometric figures on request, but when
      he tried to reproduce more complex drawings or to draw common objects he
      performed very poorly. To identify the cognitive impairment in this patient, we
      adopted two test batteries based on recent information-processing models of
      drawing. Results showed that the patient's drawing disabilities were independent
      of visuo-perceptual and executive impairments. These findings support recent
      cognitive models of drawing abilities: some intermediate stages of drawing exist
      at which information is processed to prepare and guide motor output, and which
      may be selectively disrupted after discrete cerebral lesions.

PMID- 11568402
TI  - Unusual visual symptoms and Ganser-like state due to cerebral injury: a case
      study using (18)F-deoxyglucose positron emission tomography.
AB  - Bizarre visual symptoms and absurd verbal responses to questions, in a 32-year
      old man recovering from a severe asthma episode, suggested a possible conversion
      disorder with Ganser-like symptoms. Positron Emission Tomography (PET)revealed
      bilateral lesions involving occipital association cortex and posterior temporal
      and parietal lobes, most likely infarcts from hypoxia. PET permitted correlation
      of the patient's specific cortical lesions with his unusual perceptual,
      cognitive, and speech symptoms, including Ganser-like state, to a degree not
      previously possible in such cases.

PMID- 11568403
TI  - Cortical auditory disorders: a case of non-verbal disturbances assessed with
      event-related brain potentials.
AB  - In the auditory modality, there has been a considerable debate about some aspects
      of cortical disorders, especially about auditory forms of agnosia. Agnosia refers
      to an impaired comprehension of sensory information in the absence of deficits in
      primary sensory processes. In the non-verbal domain, sound agnosia and amusia
      have been reported but are frequently accompanied by language deficits whereas
      pure deficits are rare. Absolute pitch and musicians' musical abilities have been
      associated with left hemispheric functions. We report the case of a right handed
      sound engineer with the absolute pitch who developed sound agnosia and amusia in
      the absence of verbal deficits after a right perisylvian stroke. His disabilities
      were assessed with the Seashore Test of Musical Functions, the tests of Wertheim
      and Botez (Wertheim and Botez, Brain 84, 1961, 19-30) and by event-related
      potentials (ERP) recorded in a modified 'oddball paradigm'. Auditory ERP revealed
      a dissociation between the amplitudes of the P3a and P3b subcomponents with the
      P3b being reduced in amplitude while the P3a was undisturbed. This is interpreted
      as reflecting disturbances in target detection processes as indexed by the P3b.
      The findings that contradict some aspects of current knowledge about left/right
      hemispheric specialization in musical processing are discussed and related to the
      literature concerning cortical auditory disorders.

PMID- 11568404
TI  - Left posteroventral pallidotomy results in a deficit in verbal memory.
AB  - Whilst pallidotomy is emerging as a popular approach to the treatment to
      Parkinson's disease, little is yet known about the cognitive effects of this
      procedure. This study presents 19 patients (6 right, 13 left) who were assessed
      both before and after the procedure on a battery of cognitive tests. The results
      indicate that subjects with left-sided lesions display significant decline in
      verbal memory between one and three months following the procedure. The results
      are consistent with the notion of either a classic amnesic syndrome or a deficit
      in striato-frontal working memory.

PMID- 11568405
TI  - Directed attention in Gilles de la Tourette syndrome.
AB  - Gilles de la Tourette syndrome (TS) is a basal ganglia (BG) disorder, associated
      not only with hyperkinetic movements but also with attentional impairments. This
      experiment sought to ascertain whether overt direct visual attention would
      influence tactile attentional performance in TS, via the use of a vibrotactile
      choice reaction time procedure involving biased probabilities of event
      occurrence. Participants were required to look (i.e., direct gaze) either at the
      hand receiving the most (expected) vibrations, or the hand less often stimulated
      (the unexpected), for both crossed and uncrossed arm postures. Contrary to our
      predictions, gaze did not influence attentional performance in TS patients.
      Furthermore, patients were found not to be sensitive to distributions of event
      probability; that is, they did not demonstrate normal expectancy effects like
      controls. Attentional deficits in TS (as in Parkinson's disease, another BG
      disorder) may pertain more to difficulties in holding rather than in shifting the
      focus of attention. Moreover, directing attention towards the unexpected locus in
      the crossed arm posture improved overall performance in both patients and
      controls, suggesting that increased task demands (e.g., crossed arm posture),
      and/or unexpected stimulus location, may be alleviated by directed attention.
      These impairments may stem from dysfunction in the circuits linking the frontal
      lobes with the BG.

PMID- 11568406
TI  - Paroxysmal compulsion to handle keys in a computer operator due to meningioma in
      the left supplementary motor area.
AB  - We describe the case of a computer operator who experienced paroxysmal attacks
      several times in which she felt a compulsion to handle keys with her right hand
      or actually her right hand moved involuntarily in a key-handling rhythm. Cranial
      CT and MRI revealed a mass lesion in the left medial aspect of the frontal lobe
      (supplementary motor area). After the removal of this tumor (meningioma), there
      were no more paroxysmal attacks. We suggest that voluntary movements controlled
      by the supplementary motor area were deranged by seizures provoked by the tumor.
      This case is attractive in relation to obsessive-compulsive disorder.

PMID- 11568407
TI  - The opercular-subopercular syndrome: four cases with review of the literature.
AB  - We present four cases of the 'opercular syndrome' of volitional paresis of the
      facial, lingual, and laryngeal muscles (bilateral facio-glosso-pharyngo
      masticatory paresis). Case histories and CT brain images are presented, along
      with a review of the literature concerning this long-recognized but little-known
      syndrome. The neuroanatomic basis of the syndrome classically involves bilateral
      lesions of the frontal operculum. We propose, on the basis of our cases and
      others, that the identical syndrome can arise from lesions of the corticobulbar
      tracts, not involving the cortical operculum. Our cases included one with
      bilateral subcortical lesions, one with a unilateral left opercular lesion and a
      possible, non-visualized right hemisphere lesion, one with unilateral cortical
      and unilateral subcortical pathology, and one with bilateral cortical lesions.
      These lesion localizations suggest that any combination of cortical or
      subcortical lesions of the operculum or its connections on both sides of the
      brain can produce a syndrome indistinguishable from the classical opercular
      syndrome. We propose the new term 'opercular-subopercular syndrome' to encompass
      cases with predominantly or partially subcortical lesions.

PMID- 11568408
TI  - A variant of the Kleine-Levin syndrome following head trauma.
AB  - A 19-year-old man developed the Kleine-Levin syndrome three weeks after the head
      trauma and subsequent neurosurgical evacuation of right-sided, fronto-temporal
      epidural hematoma. The expression of periodic episodes was observed for
      hypersomnolence and, to a lesser degree, for behavioral disturbances, while the
      hyperphagia was constantly present during a period of 1.5 years. These clinical
      features were associated with the focal, right-sided hypothalamic lesion and
      ipsilateral posttraumatic parenchymal temporal lobe damage on NMR imaging.

PMID- 11568409
TI  - Sleep paralysis and hallucinosis.
AB  - Background: Sleep paralysis is one of the many conditions of which visual
      hallucinations can be a part but has received relatively little attention. It can
      be associated with other dramatic symptoms of a psychotic nature likely to cause
      diagnostic uncertainty. Methods and results: These points are illustrated by the
      case of a young man with a severe bipolar affective disorder who independently
      developed terrifying visual, auditory and somatic hallucinatory episodes at sleep
      onset, associated with a sense of evil influence and presence. The episodes were
      not obviously related to his psychiatric disorder. Past diagnoses included
      nightmares and night terrors. Review provided no convincing evidence of various
      other sleep disorders nor physical conditions in which hallucinatory experiences
      can occur. A diagnosis of predormital isolated sleep paralysis was made and
      appropriate treatment recommended. Conclusions: Sleep paralysis, common in the
      general population, can be associated with dramatic auxiliary symptoms suggestive
      of a psychotic state. Less common forms are either part of the narcolepsy
      syndrome or (rarely) they are familial in type. Interestingly, sleep paralysis
      (especially breathing difficulty) features prominently in the folklore of various
      countries.

PMID- 11568410
TI  - Late-onset startle syndrome and obsessive compulsive disorder.
AB  - A case of late onset sporadic startle syndrome in a patient with a right
      posterior fossa brain tumour is reported. The exaggerated startle response did
      not respond to treatment with clonazepam. In addition to anxiety and depression,
      the patient developed obsessive- compulsive symptoms which responded to
      behavioural therapy. The possible mechanisms for this unique pattern of symptoms
      are discussed.

PMID- 11568411
TI  - Obsessive-compulsive disorder in the elderly.
AB  - Four cases of obsessive-compulsive disorder arising in late life in association
      with a presumed organic aetiology are described. Three of the four had brief
      episodes of OCD earlier in their lives. Neuropsychological assessment
      demonstrated impairments in verbal fluency and visuo-spatial tasks. No case
      exhibited global intellectual impairment. The two patients who complied with
      appropriate treatment became asymptomatic after 4-6 months.

PMID- 11568412
TI  - Psychiatric illness and behavioural problems in adults with learning disability
      and epilepsy.
AB  - We retrospectively collected data on the rate and type of psychiatric illness and
      behavioural problems on 143 adults with learning disability and epilepsy. 55%
      behavioural problems. 19% verbal aggression and temper tantrums, and 13%
      injurious behaviour. The overall rates of behavioural problems and different
      types of behaviours found in the current study cohort are similar to what was
      found before in learning disabled adults in general, as well as in epileptic and
      non-epileptic learning disabled adults. Psychiatric diagnosis was made in 12.6%
      combined diagnosis of schizophrenia, delusional disorder and schizo-affective
      disorder was most common (5%) diagnosis of depressive episode (3%) bipolar
      affective disorder.

PMID- 11568413
TI  - Speech impairment in a large sample of patients with Parkinson's disease.
AB  - This study classified speech impairment in 200 patients with Parkinson's disease
      (PD) into five levels of overall severity and described the corresponding type
      (voice, articulation, fluency) and extent (rated on a five-point scale) of
      impairment for each level. From two-minute conversational speech samples,
      parameters of voice, fluency and articulation were assessed by two trained
      raters. Voice was found to be the leading deficit, most frequently affected and
      impaired to a greater extent than other features in the initial stages.
      Articulatory and fluency deficits manifested later, articulatory impairment
      matching voice impairment in frequency and extent at the 'Severe' stage. At the
      final stage of 'Profound' impairment, articulation was the most frequently
      impaired feature at the lowest level of performance. This study illustrates the
      prominence of voice and articulatory speech motor control deficits, and draws
      parallels with deficits of motor set and motor set instability in skeletal
      controls of gait and handwriting.

PMID- 11568414
TI  - Decreased volume of the cerebral ventricles on CT images in Gilles de la
      Tourette's syndrome.
AB  - The aim of the present study was to estimate the volume of the ventricular system
      comprising lateral plus third ventricles in patients with Gilles de la Tourette's
      syndrome on computed tomographic (CT) scannings using unbiased stereological
      principles and to compare that volume with a control group. We found a
      significantly reduced ventricular volume in 24 patients with Gilles de la
      Tourette's syndrome (GTS) compared with 28 controls.

PMID- 11568415
TI  - Role of the striatum and the cerebellum in motor skill acquisition.
AB  - Motor skill acquisition was investigated in patients with Parkinson's disease
      (PD) or cerebellar dysfunction using two sensory-guided tracking tasks. The
      subjects had to learn to track a visual target (a square) on a computer screen by
      moving a joystick under two different conditions. In the unreversed task, the
      horizontal target movements were semi-predictable and could be anticipated. In
      the reversed task, the horizontal movements of a pointer which had to be kept
      within the target square were mirror-reversed to the joystick movements. PD
      patients showed intact learning of the semi-predictable task and reduced learning
      of the mirror-reversed task; patients with cerebellar dysfunction showed the
      opposite pattern. These findings are discussed in relation to the differential
      contribution of the cerebellum and the striatum to motor skill acquisition: the
      cerebellum appears to participate in the implementation of anticipatory
      movements, whereas the striatum may be critically involved in types of motor
      learning which require a high degree of internal elaboration.

PMID- 11568416
TI  - Self and body esteem perception in multiple sclerosis.
AB  - Self esteem and body esteem were examined in a group of 35 relapsing-remitting
      multiple sclerosis (MS) patients using the Body Esteem Scale (BES) and the
      Eysenck Self Esteem Scale (ESES) and compared to age and sex matched normal
      controls. There were 23 females and 12 males in the MS patient's group; average
      age 38.9 years (range: 22-52). All participants completed the self-rated BES
      evaluating the following subscales: females - sexual attractiveness, physical
      condition and weight concern; males - physical attractiveness, physical condition
      and upper body strength. In addition all participants were scored, following a
      semi-structured interview, on the ESES. Psychiatric co-morbidity was excluded
      using a semi-structured interview by the consulting psychiatrist. All evaluations
      were carried out during the remitting phase. Statistical analysis, comparing
      patients to healthy controls, demonstrated lowered self-rating of the physical
      condition (males < 0.05, females < 0.001). On the other hand, no significant
      differences were found in the physical (male) or sexual (female)--attractiveness
      subscales. The mean ESES score in the patients group was 23.2 +/- 4.0, slightly
      above the reported average. The controls mean ESES was 28.4 +/- 3.6, (P < 0.05).
      No correlation was found between self and body esteem amongst M.S. patients. This
      study emphasizes impaired perception of body esteem in multiple sclerosis
      patients even in remission. The preservation of physical and sexual
      attractiveness may be related to the non-disfiguring nature of the disease.
      Preservation of self-esteem in MS patients suggests that body-esteem should be
      the focus of supportive treatment.

PMID- 11568417
TI  - Storage of verbal associations is sufficient to activate the left medial temporal
      lobe.
AB  - Neuroimaging studies have shown that memory encoding activates the medial
      temporal lobe (MTL). Many believe that these activations are related to novelty
      but it remains unproven which is critical - novelty detection or the rich
      associative encoding it triggers. We examined MTL activation during verbal
      associative encoding using functional magnetic resonance imaging. First,
      associative encoding activated left posterior MTL more than single word encoding
      even though novelty detection was matched, indicating not only that associative
      encoding activates the MTL particularly strongly, but also that activation does
      not require novelty detection. Moreover, it remains to be convincingly shown that
      novelty detection alone does produce such activation. Second, repetitive
      associative encoding produced less MTL activation than initial associative
      encoding, indicating that priming of associative information reduces MTL
      activation. Third, re-encoding familiar associations in a well-established way
      had a minimal effect on both memory and MTL activation, indicating that MTL
      activation reflects storage of associations, not merely their initial
      representation.

PMID- 11568418
TI  - Intellectual, mnemonic, and frontal functions in dementia with Lewy bodies: A
      comparison with early and advanced Parkinson's disease.
AB  - Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common
      neuropathological marker, the presence of Lewy bodies in brain stem and basal
      forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the
      neocortex, and, in it's more common form, with Alzheimer-type pathological
      markers, particularly amyloid plaques. Published neuropsychological studies have
      focused on the differential profiles of DLB and Alzheimer's disease (AD).
      However, it is presently unclear whether DLB should be classified as a variant of
      AD or PD. In the present study we compare a healthy age-matched control group
      with three groups of patients, one with DLB, and two with PD. One of the PD
      groups was early in the course (PD-E) and the second, more advanced group (PD-A),
      was matched on severity of cognitive impairment with the DLB group. The results
      show that DLB was associated with a different pattern of neuropsychological
      impairment than the PD-A group, particularly in tests believed to be mediated by
      prefrontal cortical regions.

PMID- 11568419
TI  - Induction of a transient dysexecutive syndrome in Parkinson's disease using
      a~subclinical dose of scopolamine.
AB  - Parkinson's Disease (PD) is often associated with a subcortico-frontal syndrome
      (SCFS) that is mainly characterized by executive dysfunctions. The complete
      biochemistry of these dysfunctions remain misunderstood although many studies
      have suggested a role of the dopaminergic lesions. However, cholinergic lesions
      in this disease may also account for the SCFS occurrence. The present study has
      assessed the effects of an acute subclinical dose of scopolamine in normal
      controls and in PD patients who were devoid of cognitive deficit. Results
      indicates that PD patients but not normal controls developed a transient SCFS for
      the duration of the drug action. In contrast to other populations with
      cholinergic depletions - such as Alzheimer's disease - cholinergic blockage in PD
      exacerbates specifically the dysexecutive syndrome without inducing amnesia or
      sedation. Such a discrepancy between these two neuropsychological profiles are
      discussed in terms of the specificity of the underlying cholinergic lesions.

PMID- 11568420
TI  - Neurological soft signs in obsessive compulsive disorder: standardised assessment
      and comparison with schizophrenia.
AB  - While several studies have detected raised levels of neurological soft signs in
      patients with obsessive compulsive disorder (OCD), the specificity of these
      abnormalities remains uncertain. This study used a new standardised measure, the
      Cambridge Neurological Inventory (CNI), to assess soft signs in 51 subjects with
      OCD. Comparison was made with data on patients with schizophrenia and a non
      clinical control group from a previously reported study. Individuals with OCD
      showed raised levels of soft signs compared with non-clinical controls in many
      categories of the CNI: Motor Coordination, Sensory Integration, Primitive
      Reflexes, Extrapyramidal Signs, and Failure of Suppression. Compared with
      patients with schizophrenia, the OCD group had lower levels of neurological signs
      in some CNI categories: Hard Signs, Motor Co-ordination, Tardive Dyskinesia,
      Catatonic Signs, and Extrapyramidal Signs. However, levels of soft signs in the
      OCD group did not significantly differ from those in the schizophrenia group in
      other CNI categories: Sensory Integration, Primitive Reflexes and Failure of
      Suppression. The significance of these patterns of findings is discussed.

PMID- 11568421
TI  - The ability to orient attention in Gilles de la Tourette syndrome.
AB  - Gilles de la Tourette syndrome is characterised by tics, although patients also
      commonly present with attentional problems. This experiment aimed to ascertain
      whether TS patients have problems in orienting attention, via the use of a
      vibrotactile choice reaction time task. Participants were required to push a
      button in response to a faint vibration delivered to the index finger. Prior to
      each stimulus vibration, a pre-cue (valid, neutral or invalid) was administered
      to the finger. The performance benefits and costs participants gained from valid
      and invalid precues were calculated. Contrary to our prediction TS patients did
      not show significantly different costs or benefits. Furthermore, both patients
      and controls showed an equal and increased benefit in the crossed arm posture,
      compared to the uncrossed. These results suggest TS patients do not generally
      have problems in orienting attention. In addition, in the tactile modality, both
      patients and controls may benefit from directed attention when difficulty levels
      are maximal.

PMID- 11568422
TI  - Effects of two-year treatment with the cholinesterase inhibitor rivastigmine on
      behavioural symptoms in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is accompanied by prominent behavioural disturbances.
      They cause significant distress for both caregivers and patients and can play a
      major role in the decision to institutionalise AD patients. Recent evidence
      suggests that cholinergic deficiencies not only contribute to the memory and
      cognitive abnormalities of AD but are also responsible for some behavioural
      abnormalities seen over the course of the disease. In this study we assessed the
      ability of rivastigmine, a pseudo-irreversible cholinesterase inhibitor, to
      improve behavioural and psychopathologic symptoms in AD. The analysis included 34
      patients present in the Germanarm of the international study B303 who received
      and completed long-term treatment with rivastigmine in the open-label study B305.
      Assessments of behaviour and psychopathological symptoms were performed using the
      behavioural component of the Clinicians Interview Based Impression of Change Plus
      (CIBIC-Plus). Results show that long-term treatment with rivastigmine can slow
      the progression of behavioural and psychopathological symptoms of AD. Behavioural
      symptoms showing stabilisation included aggressiveness, activity disturbances,
      hallucinations and paranoid features. Results also suggest that patients treated
      earlier with rivastigmine may attain a greater benefit compared with patients
      whose treatment is delayed 6 months. Further studies examining the effects of
      rivastigmine on behavioural disturbances in AD are therefore warranted.

PMID- 11568423
TI  - Neurotoxic dorsal CA1 lesions versus 4 VO ischaemic lesions: behavioural
      comparisons.
AB  - Anterograde amnesia, a common consequence of transient cerebral ischaemia, has
      been attributed to cell loss in the hippocampal CA1 subfield. However, variable,
      widespread damage outside hippocampal CA1 can also occur following ischaemia. We
      compared the functional consequences of ischaemia and ibotenate acid CA1 lesions
      on 2 spatial memory tasks (water maze 'place' and 'matching-to-position') to
      address the possibility that extra-CA1 loss contributes to ischaemia-induced
      memory deficits in the rat. During place task acquisition, ischaemic rats showed
      deficits on more measures than ibotenic rats, and during a 1 min probe trial,
      only ischaemic rats were impaired. On the matching-to-position task, ibotenic
      rats showed greater impairment than ischaemic rats in terms of one-trial
      learning, whereas ischaemic rats were more impaired after Trial 2. Ischaemia and
      ibotenic acid lesions resulted in equivalent CA1 loss, but silver impregnation
      revealed additional extra-CA1 cell loss in ischaemic rats. Together with the
      greater behavioural deficits of ischaemic rats, these data indicate a role for
      extra-CA1 cell loss in ischaemia-induced memory impairments in both animals and
      humans.

PMID- 11568424
TI  - Storage and processing working memory functions in Alzheimer-type dementia.
AB  - A selective deterioration of working memory functions has been suggested as an
      explanation of the cognitive decay occurring in normal ageing as well as in
      Alzheimer-type dementia. Recent studies have highlighted that elderly people's
      limitations in working memory functions may be better interpreted when analysing
      the specific characteristics of the cognitive process (i.e., passive storage or
      active manipulation of information). In the present study, we have adapted a
      procedure used to investigate age-related memory modifications, involving both
      verbal and visuo-spatial material in tasks tapping passive and active processes,
      to investigate the deterioration associated with Alzheimer's disease. A group of
      Alzheimer patients in the early stages of the disease were matched to a control
      group of healthy elderly. Results show that Alzheimer patients performed less
      accurately than the control group in all tasks. However, the deficit was
      maximised in the case of active processes, regardless of the type of material
      used (verbal or visuo-spatial). These data highlight the importance of
      considering the amount of active processing as the key variable when interpreting
      the decay in cognitive functions in the early stages of Alzheimer's disease.

PMID- 11568425
TI  - Differential contribution of right and left amygdala to affective information
      processing.
AB  - Evidence for a differential involvement of the human left and right amygdala in
      emotional and cognitive behaviour is reviewed, with a particular emphasis on
      functional imaging results and case reports on patients with amygdalar damage.
      The available evidence allows one to conclude that there is definitely a
      hemisphere specific processing difference between the left and right amygdala.
      However, between studies the direction of the asymmetry is partly incongruent. In
      spite of this, the following tentative proposals are made: the left amygdala is
      more closely related to affective information encoding with a higher affinity to
      language and to detailed feature extraction, and the right amygdala to affective
      information retrieval with a higher affinity to pictorial or image-related
      material. Furthermore, the right amygdala may be more strongly engaged than the
      left one in a fast, shallow or gross analysis of affect-related information.

PMID- 11568426
TI  - An evolutionary hypothesis for obsessive compulsive disorder: a~psychological
      immune system?
AB  - A new hypothesis is presented within the framework of evolutionary psychology
      that attempts to explain the origins of obsessive-compulsive disorder. It is
      suggested that obsessions and compulsions originate from the overactivity of a
      mental module that the majority of humans possess and has the function of
      generating risk scenarios without voluntary intervention. It is hypothesised that
      obsessional phenomena function as an off-line risk avoidance process, designed to
      lead to risk avoidance behaviour at a future time, thus distinguishing it from
      anxiety and related phenomena as on-line emotional states, designed to lead to
      the avoidance of immediate and direct risks. Finally, the hypothesis makes a
      number of specific predictions that are testable and refutable. It is contended
      that the present hypothesis if supported by empirical evidence could serve as a
      basis for future research on this important disorder.

PMID- 11568427
TI  - Improvement of mental imagery after prism exposure in neglect: a case study.
AB  - Previous work has shown that various symptoms of unilateral neglect, including
      the pathological shift of the subjective midline to the right, may be improved by
      a short adaptation period to a prismatic shift of the visual field to the right.
      We report here the improvement of imagined neglect after prism exposure in a
      patient with a left unilateral neglect. Despite a strong neglect observed for
      mental images as well as for conventional tests, the mental evocation of left
      sided information from an internal image of the map of France map was fully
      recovered following prism adaptation to the right. This improvement could not be
      explained by the alteration of visuomotor responses induced by the prism
      adaptation. Prism adaptation may therefore act not only on sensory-motor levels
      but also on a higher cognitive level of mental space representation and/or
      exploration.

PMID- 11568428
TI  - Memory and executive function impairments after frontal or posterior cortex
      lesions.
AB  - Free recall and recognition, memory for temporal order, spatial memory and
      prospective memory were assessed in patients with frontal lobe lesions, patients
      with posterior cortex lesions and control subjects. Both patient groups showed
      equivalent memory deficits relative to control subjects on a range of free recall
      and recognition tasks, on memory for temporal order and on a prospective memory
      task. The patient groups also performed equivalently on the spatial memory task
      although only patients with frontal lobe lesions were significantly impaired.
      However, the patients with frontal lobe lesions showed an increased false alarm
      rate and made more intrusion errors relative not only to the control subjects,
      but also to the patients with poster or cortex lesions. These memory problems are
      discussed in relation to deficits in executive function and basic memory
      processes.

PMID- 11568429
TI  - Familial multiple sclerosis with repetitive relapses of manic psychosis in two
      patients (mother and daughter).
AB  - The clinical presentation of multiple sclerosis (MS) with psychiatric symptoms is
      uncommon but it is believed that MS patients are twice as likely to be afflicted
      with bipolar disorder as the general population. We report two cases (mother and
      daughter) of MS presenting with bipolar disorder in the form of recurrent manic
      psychosis and whose outcome was favourable with neuroleptics and corticosteroids.
      In both cases we found multiple hypersignal lesions on brain magnetic resonance
      imaging (MRI), especially in the right frontal lobe where we observed signs of
      activity. Apart from clinical and radiological concordance, the patients
      exhibited similar class I HLA alleles and identical class II HLA alleles. We
      focused discussion on whether there may be a common genetic susceptibility to
      both illnesses or whether MS caused psychiatric manifestations. The coincidence
      of psychiatric and neurological symptoms in most relapses supports the second
      hypothesis.

PMID- 11568430
TI  - Right amygdalar and temporofrontal activation during autobiographic, but not
      during fictitious memory retrieval.
AB  - What distinguishes the recall of real-life experiences from that of self-created,
      fictitious emotionally laden information? Both kinds of information belong to the
      episodic memory system. Autobiographic memories constitute that part of the
      episodic memory system that is composed of significant life episodes, primarily
      of the distant past. Functional imaging was used to study the neural networks
      engaged in retrieving autobiographic and fictitious information of closely
      similar content. The principally activated brain regions overlapped considerably
      and constituted temporal and inferior prefrontal regions plus the cerebellum.
      Selective activations of the right amygdala and the right ventral prefrontal
      cortex (at the level of the uncinate fascicle interconnnecting prefrontal and
      temporopolar areas) were found when subtracting fictitious from autobiographic
      retrieval. Furthermore, distinct foci in the left temporal lobe were engaged.
      These data demonstrate that autobiographic memory retrieval uses (at least in non
      brain damaged individuals) a network of right hemispheric ventral prefrontal and
      temporopolar regions and left hemispheric lateral temporal regions. It is
      concluded that it is the experiential character, its special emotional
      infiltration and its arousal which distinguishes memory of real-life from that of
      fictitious episodes. Consequently, our results point to the engagement of a bi
      hemispheric network in which the right temporo-prefrontal hemisphere is likely to
      be responsible for the affective/arousal side of information retrieval and the
      left-hemispheric temporal gyrus for its engram-like representation. Portions of
      the neural activation found during retrieval might, however, reflect re-encoding
      processes as well.

PMID- 11568431
TI  - Stereotaxic display of brain lesions.
AB  - Traditionally lesion location has been reported using standard templates, text
      based descriptions or representative raw slices from the patient's CT or MRI
      scan. Each of these methods has drawbacks for the display of neuroanatomical
      data. One solution is to display MRI scans in the same stereotaxic space popular
      with researchers working in functional neuroimaging. Presenting brains in this
      format is useful as the slices correspond to the standard anatomical atlases used
      by neuroimagers. In addition, lesion position and volume are directly comparable
      across patients. This article describes freely available software for presenting
      stereotaxically aligned patient scans. This article focuses on MRI scans, but
      many of these tools are also applicable to other modalities (e.g. CT, PET and
      SPECT). We suggest that this technique of presenting lesions in terms of images
      normalized to standard stereotaxic space should become the standard for
      neuropsychological studies.

PMID- 11568432
TI  - A study of emotionalism in patients undergoing rehabilitation following severe
      acquired brain injury.
AB  - The present study describes the phenomenon of emotionalism in a sample of brain
      injured patients of mixed aetiology, with a view to identifying issues relevant
      to clinical management, and possible causal factors. 82 subjects with severe
      acquired brain injury undergoing rehabilitation participated in a structured
      interview in which they were asked to report the presence/absence of emotionalism
      and degree of distress associated with it. Their overt crying behaviour was also
      observed and recorded. Independent variables that predicted crying during the
      interview were identified using a multiple logistic regression procedure.
      Prevalence rates of emotionalism-tearfulness were high in this sample (52% self
      report, 36--41% Emotionalism-laughter was much less common (13%) Emotionalism
      tearfulness was usually accompanied by negative affect, occurred in response to
      identifiable precipitants, and was often controllable. It was associated with
      major personal distress in about half the subjects who reported it. Independent
      variables which predicted crying behaviour were female gender and focal damage to
      the right cerebral hemisphere. It is concluded that an increased readiness to cry
      is common in people with severe acquired brain injury of mixed aetiology. The
      behaviour is meaningful, though not always distressing. The intensity of the
      behaviour is variable, and it may be most appropriate to regard emotionalism as a
      dimension rather than a syndrome. Implications for clinical management are
      discussed.

PMID- 11568433
TI  - Dysexecutive syndrome in schizophrenia: A cross-cultural comparison between
      Japanese and British patients.
AB  - This study tested the hypothesis that the dysexecutive syndrome of schizophrenia
      is impervious to cultural differences. 18 Japanese and 22 British patients and 14
      Japanese and 19 British control subjects were compared on the BADS (Behavioural
      Assessment of Dysexecutive Syndrome), a comprehensive neuropsychological
      assessment battery, designed for 'ecological validity', and other measures of
      frontal executive functions (EFs). Both cultural groups of schizophrenic patients
      showed equally severe impairment in most executive tests including the BADS
      (verbal fluency and intelligence were less impaired). Irrespective of cultural
      origin, similar neuropsychological deficits were found in patients with minimal
      intellectual deterioration. Our study suggests that socio-cultural background
      does not affect the dysexecutive profile of schizophrenia very much, and that
      neuropsychological assessment may possibly provide added clinical information
      relevant to the management and rehabilitation of schizophrenic patients across
      different cultures.

PMID- 11568434
TI  - Distinctive features in the SelB family of elongation factors for selenoprotein
      synthesis. A glimpse of an evolutionary complexified translation apparatus.
AB  - The last ten years have seen a dramatic increase in our understanding of the
      molecular mechanism allowing specific incorporation of selenocysteine into
      selenoproteins. Whether in prokaryotes or eukaryotes, this incorporation requires
      several gene products, among which the specialized elongation factor SelB and the
      tRNA(Sec) play a pivotal role. While the molecular actors have been discovered
      and their role elucidated in the eubacterial machinery, recent data from our and
      other laboratories pointed to a higher degree of complexity in archaea and
      eukaryotes. These findings also revealed that more needs to be discovered in this
      area. This review will focus on phylogenetic aspects of the SelB proteins. In
      particular, we will discuss the concerted evolution that occurred within the
      SelB/tRNA(Sec) couples, and also the distinctive roles carried out by the SelB C
      terminal domains in eubacteria on the one side, and archaea and eukaryotes, on
      the other.

PMID- 11568435
TI  - RNA binding proteins and selenocysteine.
AB  - Selenocysteine is incorporated into protein by a complex co-translational
      mechanism that involves both cis and trans acting factors. Among the trans-acting
      factors are RNA binding proteins that interact with the selenoprotein 3' UTRs at
      a sequence known as the selenocysteine insertion sequence (SECIS). These factors
      are generally referred to as SBPs, and in this review we will discuss the history
      of the SBPs, and give a detailed description of the recently identified SBP2
      which is the only SBP known to be required for Sec insertion. The mechanism by
      which SBP2 may be involved in this process will be discussed.

PMID- 11568436
TI  - Selenocysteine incorporation directed from the 3'UTR: characterization of
      eukaryotic EFsec and mechanistic implications.
AB  - The mechanism of selenocysteine incorporation in eukaryotes has been assumed for
      almost a decade to be inherently different from that in prokaryotes, due to
      differences in the architecture of selenoprotein mRNAs in the two kingdoms. After
      extensive efforts in a number of laboratories spanning the same time frame, some
      of the essential differences between these mechanisms are finally being revealed,
      through identification of the factors catalyzing cotranslational selenocysteine
      insertion in eukaryotes. A single factor in prokaryotes recognizes both the
      selenoprotein mRNA, via sequences in the coding region, and the unique
      selenocysteyl-tRNA, via both its secondary structure and amino acid. The
      corresponding functions in eukaryotes are conferred by two distinct but
      interacting factors, one recognizing the mRNA, via structures in the 3'
      untranslated region, and the second recognizing the tRNA. Now, with these factors
      in hand, crucial questions about the mechanistic details and efficiency of this
      intriguing process can begin to be addressed.

PMID- 11568437
TI  - A model for Sec incorporation with the regions upstream of the UGA Sec codon to
      play a key role.
AB  - For eukaryotic selenoprotein mRNAs, it has been proposed that the SECIS element
      in the 3'-UTR is required for recognition of UGA as a Sec codon. Some proteins
      which bind to SECIS (SBP) have been reported. However, it is not clear how the
      SECIS element in the 3'-UTR can mediate Sec insertion far at the in-frame UGA Sec
      codons. The idea that there must be a signal near the UGA Sec codon is still
      being considered. Therefore, we searched for a protein which binds to an RNA
      sequence surrounding the UGA Sec codon on human GPx mRNA. We found a protein,
      prepared from bovine brain microsomes, which strongly bound to the RNA fragment
      upstream of the UGA Sec codon but not to the RNA sequence downstream of the UGA
      codon. This protein also bound to the SECIS sequence in the 3'-UTR of human GPx,
      and this binding to SECIS was competed with the RNA fragment upstream of the UGA
      Sec codon. We also obtained the similar results with the RNA fragments of type I
      iodothyronine 5'-deiodinase (5'DI) mRNAs. Comparison of such RNA fragments with
      SECIS fragments revealed similarities in the region upstream of the in-frame UGA
      Sec codon of several Se-protein mRNAs. The study thus favors a novel model of Sec
      incorporation at the UGA Sec codon that involves the regions upstream of the UGA
      codon of mRNAs of mammalian selenoproteins. This model explains that the stem
      loop structure covering the UGA codon is recognized by SBP and how the UGA Sec
      codon escapes from attack by eRF.

PMID- 11568438
TI  - Evidence that selenium deficiency results in the cytoplasmic decay of GPx1 mRNA
      dependent on pre-mRNA splicing proteins bound to the mRNA exon-exon junction.
AB  - Studies of transcripts for the selenoprotein glutathione peroxidase 1 (GPx1) have
      provided remarkable evidence for the coupling of pre-mRNA splicing in the nucleus
      and mRNA translation in the cytoplasm. Such evidence derives from the initial
      finding that GPx1 mRNA is a natural substrate of nonsense-mediated decay. Here,
      recent work on GPx1 RNA metabolism is reviewed and future directions of study are
      defined.

PMID- 11568439
TI  - Stability of gastrointestinal glutathione peroxidase mRNA in selenium deficiency
      depends on its 3'UTR.
AB  - Selenoproteins decrease upon selenium-deprivation according to their hierarchical
      ranking. Whereas classical glutathione peroxidase (cGPx) responds to decreased
      selenium supply with a complete loss of protein and a marked reduction of mRNA
      levels, gastrointestinal glutathione peroxidase (GI-GPx) remains detectable and
      its mRNA is stable. The impact of the 3'UTR on cGPx and GI-GPx mRNA stability was
      studied in stably transfected HepG2 cells with combinations of mutually exchanged
      coding regions and 3'UTRs of human cGPx and GI-GPx. Stability of chimeric mRNAs
      was measured by competitive RT-PCR. We found that GI-GPx 3'UTR is sufficient to
      stabilize its own mRNA but not that of cGPx.

PMID- 11568440
TI  - Functional analysis of prokaryotic SELB proteins.
AB  - Since the discovery of selenocysteine as the 21st amino acid considerable
      progress has been made in elucidating the system responsible for its insertion
      into proteins. Elongation factor SELB, whose amino-terminal part shows homology
      to EF-Tu, was found to be the key component mediating delivery of selenocysteyl
      tRNA(Sec) to the ribosomal A site. It exhibits a distinct tertiary structure
      comprising binding sites for guanosine nucleotides, the cognate tRNA, an mRNA
      secondary structure (SECIS element) and presumably ribosomal components. The
      kinetics of interaction of SELB with its ligands have been studied in detail. GDP
      was found to bind with about 20-fold lower affinity than GTP and to be in rapid
      exchange, which obviates the need for a guanosine nucleotide exchange factor. The
      affinity of SELB for the SECIS element is in the range of 1 nM and further
      increases upon binding of selenocysteyl-tRNA(Sec) to the protein. This supports
      the model that SELB forms a tight quaternary complex on the SECIS element which
      is loosened after insertion of the tRNA into the ribosomal A site and the
      concomitant hydrolysis of GTP.

PMID- 11568441
TI  - An extended Escherichia coli "selenocysteine insertion sequence" (SECIS) as a
      multifunctional RNA structure.
AB  - The genetic code, once thought to be rigid, has been found to permit several
      alternatives in its reading. Interesting alternative relates to the function of
      the UGA codon. Usually, it acts as a stop codon, but it can also direct the
      incorporation of the amino acid selenocysteine into a polypeptide. UGA-directed
      selenocysteine incorporation requires a cis-acting mRNA element called the
      "selenocysteine insertion sequence" (SECIS) that can form a stem-loop RNA
      structure. Here we discuss our investigation on the E. coli SECIS. This includes
      the follows: 1) The nature of the minimal E. coli SECIS. We found that in E. coli
      only the upper-stem and loop of 17 nucleotides of the SECIS is necessary for
      selenocysteine incorporation on the condition that it is located in the proper
      distance from the UGA [34]; 2) The upper stem and loop structure carries a bulged
      U residue that is required for selenocysteine incorporation [34] because of its
      interaction with SelB; and 3) We described an extended fdhF SECIS that includes
      the information for an additional function: The prevention of UGA readthrough
      under conditions of selenium deficiency [35]. This information is contained in a
      short mRNA region consisting of a single C residue adjacent to the UGA on its
      downstream side, and an additional segment consisting of the six nucleotides
      immediately upstream from it. These two regions act independently and additively
      and probably through different mechanisms. The single C residue acts as itself;
      the upstream region acts at the level of the two amino acids, arginine and
      valine, for which it codes. These two codons at the 5' side of the UGA correspond
      to the ribosomal E and P sites. Finally, we present a model for the E. coli fdhF
      SECIS as a multifunctional RNA structure containing three functional elements.
      Depending on the availability of selenium the SECIS enables one of two
      alternatives for the translational machinery: Either selenocysteine incorporation
      into a polypeptide or termination of the polypeptide chain.

PMID- 11568442
TI  - Utilization of selenocysteine as a source of selenium for selenophosphate
      biosynthesis.
AB  - Selenophosphate synthetase (SPS), the selD gene product from Escherichia coli,
      catalyzes the biosynthesis of monoselenophosphate from selenide and ATP.
      Characterization of selenophosphate synthetase revealed the determined K(m) value
      for selenide is far above the optimal concentration needed for growth and
      approached levels which are toxic. Selenocysteine lyase enzymes, which decompose
      selenocysteine to elemental selenium (Se(0)) and alanine, were considered as
      candidates for the control of free selenium levels in vivo. The ability of a
      lyase protein to generate Se(0) in the proximity of SPS maybe an attractive
      solution to selenium toxicity as well as the high K(m) value for selenide.
      Recently, three E. coli NifS-like proteins, CsdB, CSD, and IscS, were
      characterized. All three proteins exhibit lyase activity on L-cysteine and L
      selenocysteine and produce sulfane sulfur, S(0), or Se(0) respectively. Each
      lyase can effectively mobilize Se(0) from L-selenocysteine for selenophosphate
      biosynthesis.

PMID- 11568443
TI  - Selenoprotein synthesis in archaea.
AB  - The availability of the genome sequences from several archaea has facilitated the
      identification of the encoded selenoproteins and also of most of the components
      of the machinery for selenocysteine biosynthesis and insertion. Until now,
      selenoproteins have been identified solely in species of the genera Methanococcus
      (M.) and Methanopyrus. Apart from selenophosphate synthetase, they include only
      enzymes with a function in energy metabolism. Like in bacteria and eukarya,
      selenocysteine insertion is directed by a UGA codon in the mRNA and involves the
      action of a specific tRNA and of selenophosphate as the selenium donor. Major
      differences to the bacterial system, however, are that no homolog for the
      bacterial selenocysteine synthase was found and, especially, that the SECIS
      element of the mRNA is positioned in the 3' nontranslated region. The
      characterisation of a homolog for the bacterial SelB protein showed that it does
      not bind to the SECIS element necessitating the activity of at least a second
      protein. The use of the genetic system of M. maripaludis allowed the heterologous
      expression of a selenoprotein gene from M. jannaschii and will facilitate the
      elucidation of the mechanism of the selenocysteine insertion process in the
      future.

PMID- 11568444
TI  - Evolution of selenocysteine-containing proteins: significance of identification
      and functional characterization of selenoproteins.
AB  - In the genetic code, UGA serves as either a signal for termination or a codon for
      selenocysteine (Sec). Sec rarely occurs in protein and is different from other
      amino acids in that much of the biosynthetic machinery governing its
      incorporation into protein is unique to this amino acid. Sec-containing proteins
      have diverse functions and lack a common amino acid motif or consensus sequence.
      Sec has previously been considered to be a relic of the primordial genetic code
      that was counter-selected by the presence of oxygen in the atmosphere. In the
      present report, it is proposed that Sec was added to the already existing genetic
      code and its use has accumulated during evolution of eukaryotes culminating in
      vertebrates. The more recently evolved selenoproteins appear to take advantage of
      unique redox properties of Sec that are superior to those of Cys for specific
      biological functions. Further understanding of the evolution of selenoproteins as
      well as biological properties and biomedical applications of the trace element
      selenium requires identification and functional characterization of all mammalian
      selenoproteins.

PMID- 11568445
TI  - Glutathione peroxidase-1 gene knockout on body antioxidant defense in mice.
AB  - To determine the in vivo role of cellular glutathione peroxidase (E.C.1.11.1.9,
      GPX1), we challenged the GPX1 knockout [GPX1(-/-)], the GPX1 overexpressing
      [GPX1(+)], and their respective wild-type (WT) mice of different Se and vitamin E
      status with acute oxidative stress. After these mice were injected with pro
      oxidants paraquat or diquat at 12 to 125 mg/kg of body weight, their survival
      rate and time were a function of their GPX1 activity levels. The GPX1 protection
      was associated with attenuation of NADPH and NADH oxidation, protein carbonyl and
      F(2)-isoprostanes formation, and alanine transaminase release in various tissues,
      and was irreplaceable by high levels of dietary vitamin E or other
      selenoproteins. The GPX1 expression was also protective against moderate
      oxidative stress induced by low levels of paraquat or diquat, particularly in the
      Se-deficient mice. Alteration of GPX1 expression showed no impact on the
      expression of other selenoproteins and antioxidant enzymes in unstressed mice.
      Total Se content in liver of the Se-adequate GPX1(-/-) mice was reduced by 60%
      the WT controls. In conclusion, normal expression of GPX1 is essential and
      overexpression of GPX1 is beneficial to protect mice against acute oxidative
      stress.

PMID- 11568446
TI  - Functions of GI-GPx: lessons from selenium-dependent expression and intracellular
      localization.
AB  - Gastro intestinal glutathione peroxidase (GI-GPx) is one of the four distinct
      mammalian selenoperoxidases. It had been reported to be restricted to the
      gastrointestinal tract but has more recently been identified also in human liver
      and some tumor cell lines. GI-GPx ranks high in the hierarchy of selenoproteins.
      The GI-GPx mRNA rather increases than decreases in selenium deficiency. GI-GPx
      protein responds poorly to selenium deprivation and increases fast upon
      resupplementation. Putative biological roles of GI-GPx, e.g. protection against
      food-born hydroperoxides, redox-regulation of proliferation or apoptosis, and
      modulation of mucosal immunity, are discussed in the light of cellular and
      subcellular distribution, transcriptional regulation and observations with k.o.
      mice.

PMID- 11568447
TI  - Plasma selenium in specific and non-specific forms.
AB  - Selenium is present in plasma and tissues in specific and non-specific forms. The
      experiments reported here were carried out to clarify some factors that affect
      these forms of the element in plasma. A selenium-replete human subject was given
      400 microg of selenium daily for 28 days as selenomethionine and, in a separate
      experiment, as selenate. The selenomethionine raised plasma and albumin selenium
      concentrations. Selenate did neither. The molar ratio of methionine to selenium
      in albumin was approximately 8000 under basal and selenate-supplemented
      conditions but 2800 after selenomethionine supplementation. This demonstrates
      that selenium from selenomethionine, but not selenium from selenate, can be
      incorporated into albumin, presumably as selenomethionine in the methionine pool.
      Selenocysteine incorporation into albumin was studied in rats using (75)Se
      selenocysteine. No evidence was obtained for incorporation of (75)Se into albumin
      after exogenous administration or endogenous synthesis of (75)Se-selenocysteine.
      Thus, selenocysteine does not appear to be incorporated non-specifically into
      proteins as is selenomethionine. These findings are in support of
      selenomethionine being a non-specific form of selenium that is metabolized as a
      constituent of the methionine pool and is unaffected by specific selenium
      metabolic processes. No evidence was found for non-specific incorporation of
      selenium into plasma proteins when it was administered as selenate or as
      selenocysteine. These forms of the element appear to be metabolized by specific
      selenium metabolic processes.

PMID- 11568448
TI  - Selenium: a key element that controls NF-kappa B activation and I kappa B alpha
      half life.
AB  - Treatment of mammalian cells with hydrogen peroxide induces the nuclear
      translocation of the transcription factor NF-kappa B and its binding to kappa B
      DNA sequences present in the promoter region of numerous genes. The role of
      selenium in NF-kappa B activation was analyzed in human T47D cells overexpressing
      the seleno-dependent detoxifiant enzyme glutathione peroxidase. Following
      exposure to H(2)O(2), these cells showed a seleno-dependent decreased
      accumulation of intracellular ROS and NF-kappa B activation. This phenomenon was
      correlated with an inhibition of the nuclear translocation of NF-kappa B (p50
      subunit) and with an absence of I kappa B alpha degradation. We also report that
      the half-life of I kappa B alpha in untreated cells was increased two-fold by the
      overexpression of active glutathione peroxidase. These results suggest that
      selenium is a key element that through its modulation of glutathione peroxidase
      activity can inhibit NF-kappa B activation and can up-regulate I kappa B alpha
      normal half life.

PMID- 11568449
TI  - Selenium and signal transduction: roads to cell death and anti-tumour activity.
AB  - Accumulated evidence from prospective studies, intervention trials and studies on
      animal models of cancer have suggested a strong inverse correlation between
      selenium intake and cancer incidence. Several putative mechanisms have been
      suggested to mediate the chemopreventive activities of selenium: of these, the
      inhibition of cellular proliferation and the induction of apoptosis are
      particularly attractive. The mitogen activated protein kinase (MAPK) pathways are
      known to be important regulators of cell death and our recent work has focused on
      the involvement of these pathways in selenium-induced apoptosis in primary
      cultures of oral cancers and corresponding normal mucosa derived from biopsy
      material. Using this system, the oral carcinoma cells were found to have enhanced
      sensitivity to apoptosis when treated with certain selenium compounds compared to
      normal oral mucosa. Induction of Fas ligand was associated with selenium-induced
      apoptosis. Signal transduction studies suggests that selenium induces several
      changes in the MAPK signalling pathways but functional intervention/inhibitor
      studies indicate that activation of the JNK pathway seems to be most important.

PMID- 11568450
TI  - Modulation of selenoprotein P expression by TGF-beta(1) is mediated by Smad
      proteins.
AB  - Selenoprotein P (SeP) is a selenium-rich plasma protein which accounts for more
      than 50% this study, the effect of TGF-beta(1) on the expression of SeP in the
      human liver cell line HepG2 was investigated. Western analysis revealed a dose
      dependent reduction of SeP content in cell supernatant. RT-PCR analysis of SeP
      mRNA expression demonstrated a marked inhibition and a reporter gene under
      control of the SeP promoter was negatively regulated by TGF-beta(1). Smad
      proteins are the transcriptional mediators of TGF-beta signaling. A putative Smad
      binding element (SBE) is present in the SeP promoter. In electrophoretic-mobility
      shift assays, TGF-beta(1) enhanced the binding of nuclear proteins to this SBE.
      Overexpression of Smad3 and 4 resulted in a downregulation of SeP-promoter
      activity whereas deletion of the SBE led to a loss of TGF-beta(1) responsiveness.
      We conclude that SeP expression is modulated by the binding of Smad3/4 complexes
      to a functional SBE in the SeP promoter.

PMID- 11568451
TI  - The Drosophila selenophosphate synthetase (selD) gene is required for development
      and cell proliferation.
AB  - To study the function of selenoproteins in development and growth we have used a
      lethal mutation (selD(ptuf)) of the Drosophila homologous selenophosphate
      synthetase (selD) gene. This enzyme is involved in the selenoprotein
      biosynthesis. The selD(ptuf) loss-of-function mutation causes aberrant cell
      proliferation and differentiation patterns in the brain and imaginal discs, as
      deduced from genetic mosaics, patterns of gene expression and analysis of cell
      cycle markers. In addition to that, selenium metabolism is also necessary for the
      ras/MAPKinase signal tansduction pathway. Therefore, the use of Drosophila
      imaginal discs and brain and in particular the selD(ptuf) mutation, provide an
      excellent model to investigate the role of selenoproteins in the regulation of
      cell proliferation, growth and differentiation.

PMID- 11568452
TI  - An analysis of cancer prevention by selenium.
AB  - The nutritional functions of selenium (Se) are recognized as being due to a
      number of Se-containing proteins. It is not clear, however, whether any of these
      function in the anti-tumorigenic effects of Se most of which have been
      demonstrated for Se exposures greater than those required for selenoprotein
      expression. Indeed, other anti-tumorigenic mechanisms have been demonstrated for
      certain Se-metabolites. The Nutritional Prevention of Cancer Trial found
      supplemental Se (200 microg/day, as Se-enriched yeast) to be associated with
      significant reductions in cancer risks in subjects with pre-treatment plasma Se
      concentrations below ca. 120 ng/ml (1.5 nmoles/ml), which level would appear to
      require food-Se intakes of ca. 1.5 microg/kg body weight/day. However, the
      putative anti-carcinogenic Se-metabolite(s) should be more relevant than total
      plasma Se as a supplementation target for cancer prevention. These may be
      components of the non-protein-bound fraction of Se in plasma, which constitutes 2
      4% of total plasma Se.

PMID- 11568453
TI  - Effect of selenium on the immunocompetence of patients with head and neck cancer
      and on adoptive immunotherapy of early and established lesions.
AB  - Supplementation with 200 microg/day of sodium selenite during therapy for
      squamous cell carcinoma (SQCC) of the head and neck, e.g., surgery, radiation, or
      surgery and radiation, resulted in a significantly enhanced cell-mediated immune
      responsiveness. The enhanced responsiveness was evident during therapy and
      following conclusion of therapy. In contrast, patients in the placebo arm of the
      study showed a decline in immune responsiveness during therapy. The results from
      studies on mice inoculated with SQCC cells expressing the receptor for
      interleukin-2 (IL-2) and supplemented with Se (2.00 ppm) indicated that Se
      significantly retards the clinical appearance of tumors; peritumoral injections
      of 2,000 IU of IL-2 resulted in 50% reduction in the size of established tumors
      and 72% of early tumors. The combined data suggested that local immunotherapy
      with IL-2 in hosts supplemented with Se may represent an effective modality of
      treatment for the prevention of recurrences at the site of conventionally treated
      primary tumors.

PMID- 11568454
TI  - Se-methylselenocysteine activates caspase-3 in mouse mammary epithelial tumor
      cells in vitro.
AB  - Se-methylselenocysteine (MSC) inhibits mouse mammary epithelial tumor cell (TM6)
      growth. When synchronized TM6 cells were exposed to 50 microM MSC, either for 30
      minutes or continuous, the 116 kDa poly(ADP-ribose)polymerase (PARP) was cleaved
      to an 85 kDa fragment indicative of cells undergoing apoptosis. The earliest
      cleaved PARP appears at 24 hr time point followed by elevated levels of 85 kDa
      fragment at 34 hr and 48 hr time points when the cells were exposed to continuous
      treatment with MSC. Results also showed that MSC increased caspase-3 activity at
      24 hr time point. In addition, continuous treatment with MSC induced DNA
      fragmentation at 34 hr and 48 hr time points with caspase-3 gene expression
      moderately increased at 16 hr and 24 hr time points. Caspase-6 and -8 were also
      involved in the MSC-induced apoptosis but to a lesser extent. These results
      suggest that MSC mediates cleavage of PARP and apoptosis by activating one or
      more caspases in synchronized TM6 cells and the events are dependent on the
      duration of treatment.

PMID- 11568455
TI  - Cloning of phospholipid hydroperoxide glutathione peroxidase (PHGPx) as an anti
      apoptotic and growth promoting gene of Burkitt lymphoma cells.
AB  - Burkitt Lymphoma (BL) cells are highly sensitive to suboptimal growth conditions
      and undergo apoptosis when seeded at low cell density or reduced serum
      concentration. Irradiated fibroblasts or a mix of pruvate, alpha-thioglycerol,
      and bathocuproine disulfonate can protect BL cells from apoptosis induced by
      lowering cell density or serum concentration by promoting cystine uptake in the
      cells. The availability of cystine is the limiting factor for glutathione
      biosynthesis in BL cells and thus for the ability of the cells to cope with
      oxidative stress. We have set up an expression cloning strategy to clone genes
      that protect BL cells from apoptosis induced by low cell density and/or serum.
      Using this approach we have cloned among others the cDNA for Phospholipid
      Hydroperoxide Glutathione Peroxidase (PHGPx).

PMID- 11568456
TI  - Selenium (Se) from high-selenium broccoli is utilized differently than selenite,
      selenate and selenomethionine, but is more effective in inhibiting colon
      carcinogenesis.
AB  - The reduction in incidence of chemically-induced colon cancer by foods high in
      selenium (Se) was investigated in Fisher-344 rats. The foods used were high-Se
      broccoli (produced in a greenhouse by addition of selenate to the media
      surrounding the plant roots) and a processed high-Se wheat product (made by
      milling high-Se wheat purchased from a seleniferous area). Weanling rats were fed
      diets containing different amounts of Se from these foods or from selenium salts
      (selenite and selenate). Early in the experiment the animals were injected with a
      chemical carcinogen. After 11 weeks on diets animals were killed and the colons
      examined for preneoplastic lesions (aberrant crypts foci, ACF). ACF were
      significantly reduced in animals fed supra-nutritional amounts of Se from
      broccoli, despite the finding that Se from broccoli was poorly bioavailable.
      Supra-nutritional amounts of Se from high-Se processed wheat also significantly
      reduced aberrant crypts (AC), although pure selenomethionine, (the predominant
      chemical form of Se in wheat), did not significantly reduce AC. These results
      emphasize the need to study Se in food forms, and not extrapolate from previous
      studies using pure chemical forms in cancer inhibition studies. They also
      demonstrate that foods with high Se bioavailability are not necessarily the most
      efficacious for cancer incidence reduction.

PMID- 11568457
TI  - The effect of a selenium supplementation on the outcome of patients with severe
      systemic inflammation, burn and trauma.
AB  - Patients with systemic inflammatory response syndrome (SIRS) and sepsis exhibit
      decreased plasma selenium and glutathione peroxidase activity. This has been
      shown in several clinical studies. Moreover, the degree of selenium deficiency
      correlates with the severity of the disease and the incidence of mortality.
      Patients with SIRS and sepsis are exposed to severe oxidative stress.
      Selenoenzymes play a major role in protecting cells against peroxidation,
      especially lipid peroxidation and are involved in the regulation of inflammatory
      processes. Therefore, selenium substitution in those patients might be effective
      in the prevention of multiorgan failure. The results of randomised clinical
      trials investigating selenium substitution in critical ill patients with
      inflammation are reviewed. In two independently performed randomised, prospective
      clinical trials, including patients with systemic inflammatory response syndrome
      or sepsis, the supplementation of selenium revealed a significant reduction in
      multiorgan failure and, especially, a lower incidence of acute renal failure and
      respiratory distress syndrome. One of those trials also could demonstrate a
      significant reduction of mortality in the most severely ill patients. Two other
      studies, where selenium together with other trace elements or a mixture of
      antioxidants were used in the treatment of patients with severe burn injuries or
      trauma showed a significant reduction in the secondary infection rate, including
      sepsis. Thus, selenium supplementation seems to improve the outcome of patients
      with SIRS, sepsis and severe injury, however, pivotal prospective clinical trials
      with sufficient statistical power are now necessary to finally prove the efficacy
      of a selenium supplementation in these diseases.

PMID- 11568458
TI  - Glutathione peroxidase and viral replication: implications for viral evolution
      and chemoprevention.
AB  - It is likely that several of the biological effects of selenium are due to its
      effects on selenoprotein activity. While the effects of the anti-oxidant
      selenoprotein glutathione peroxidase (GPx) on inhibiting HIV activation have been
      well documented, it is clear that increased expression of this enzyme can
      stimulate the replication and subsequent appearance of cytopathic effects
      associated with an acutely spreading HIV infection. The effects of GPx on both
      phases of the viral life cycle are likely mediated via its influence on signaling
      molecules that use reactive oxygen species, and similar influences on signaling
      pathways may account for some of the anti-cancer effects of selenium. Similarly,
      selenium can alter mutagenesis rates in both viral genomes and the DNA of
      mammalian cells exposed to carcinogens. Comparisons between the effects of
      selenium and selenoproteins on viral infections and carcinogenesis may yield new
      insights into the mechanisms of action of this element.

PMID- 11568459
TI  - PHGPx and spermatogenesis.
AB  - PHGPx of rat sperm mitochondrial capsule is cross-linked and inactive. The enzyme
      is in part released in an active form by mercaptoethanol. Treatment with H(2)O(2)
      of reduced and solubilised capsule proteins, in the absence of any added
      reductant, results in: i) H(2)O(2) consumption which depends on the presence of
      both, PHGPx activity and protein thiols; ii) protein thiol oxidation with a
      stoichiometry of 2 equivalents of thiol per mole of hydroperoxide and, iii) PHGPx
      inactivation and cross-linking. SDS-PAGE analysis of monobromobimane-labeled
      proteins, following incubation with H(2)O(2), shows that the oxidation takes
      place in specific bands in the area of 20~kDa. It is concluded that the protein
      thiol peroxidase activity of PHGPx is responsible for cross-linking proteins in
      the mammalian sperm capsule and accounts for the selenium dependency of
      spermatogenesis.

PMID- 11568460
TI  - Modulation of steroidogenesis by selenium in a novel adrenal cell line developed
      using targeted tumorigenesis.
AB  - Glutathione peroxidase (GPx-1) is a selenoenzyme that metabolizes H(2)O(2), a
      source of potentially toxic free radicals. Steroidogenesis is markedly inhibited
      by H(2)O(2) in vitro. OBJECTIVE: to study the effects of selenium deficiency on
      GPx activity and adrenal steroidogenesis in a novel adrenal cell line developed
      using targeted tumorigenesis. METHODS: AN4Rppc7 cells were grown for 7 days in
      serum-free medium. 8-Br-cAMP-stimulated concentrations of steroid hormones were
      measured by RIA. StAR (Steroid Acute Reactive Protein) mRNA was measured by
      Northern blot. RESULTS: selenium deficiency caused a 99% There was a 51%,
      progesterone, corticosterone and aldosterone production, respectively (p<0.05 by
      ANOVA). StAR mRNA was not affected by selenium. CONCLUSIONS: selenium deficiency
      causes a marked decrease in GPx activity. Decreased steroid hormone production
      occurs for selenium concentrations equal or lower than 5 nM. The absence of
      changes in StAR mRNA content suggests that selenium deficiency does not affect
      cholesterol access to the mitochondria.

PMID- 11568461
TI  - Bioremediation of selenium-contaminated sediments and water.
AB  - Selenium (Se) is a contaminant of agricultural irrigation-drainage water in the
      western United States, and the cause of wildlife deaths and grotesque
      deformities. Some approaches in reducing the toxic Se concentrations from
      contaminated sediments and water have been proposed, but most of these tend to be
      costly or ineffective. Bioremediation through microbial transformations of toxic
      Se species into nontoxic forms is being considered as an effective remedial
      alternative. The microbial reduction of toxic oxyanions of Se (SeO(4)(2-) and
      SeO(3)(2-)) into insoluble Se(0) or methylation of these species to
      dimethylselenide (DMSe) has been accepted as a potential bioremediation strategy
      for cleanup of Se-contaminated water and sediments. By conducting a series of
      laboratory, bench-scale and field studies, we have thoroughly investigated the
      remedial potential of these approaches. It was observed that microorganisms,
      particularly Enterobacter cloacea, are very active in reduction of Se oxyanions
      present in irrigation drainage water, into insoluble Se(0) and, by monitoring
      various environmental conditions and addition of organic amendments, the process
      could be stimulated manifold. Similarly, the process of biomethylation of Se in
      soil sediments and water was found active and highly dependent on specific carbon
      amendments (pectin and proteins), pH, temperature, moisture, aeration and
      activators (cofactors). Moreover, Se biomethylation was protein/peptide-limited
      rather than nitrogen-, amino acid- or carbon-limited. Crude casein and its
      components were equally stimulatory producing a >50-fold enhancement in DMSe
      yield. Methionine and methyl cobalamin stimulated DMSe production by Alternaria
      alternata, indicating that the coenzyme may mediate the transfer of a methyl
      group to the Se atom. An acute toxicity test involving inhalation of DMSe by rats
      revealed that DMSe is nontoxic. Experiments were scaled up from laboratory
      studies to field plots to verify the feasibility of this bioremediation approach.
      Based upon the promising results of these studies, a biotechnology prototype was
      developed which could be applicable for cleanup of polluted sediments and water
      throughout the western United States.

PMID- 11568462
TI  - The green technology of selenium phytoremediation.
AB  - Selenium toxicity is encountered in arid and semi-arid regions of the world with
      alkaline, seleniferous soils derived from marine sediments. Once present in soils
      and waters at high concentrations, Se is very complicated and highly expensive to
      remove with conventional physical and chemical techniques. Phytoremediation is a
      plant-based technology that is being considered for managing Se in central
      California soils. The technology involves the use of plants in conjunction with
      microbial activity associated with the plants to extract, accumulate, and
      volatilize Se. Once absorbed by plant roots, Se is translocated to the shoot
      where it may be harvested and removed from the site. Therefore, plant species
      used for phytoremediation of Se-laden soils may by plant uptake and
      volatilization minimize the Se load eventually entering agricultural effluent and
      the harvested crop can be carefully blended with animal forage and fed to animals
      in Se-deficient areas.

PMID- 11568463
TI  - Removal of soluble selenium by a selenate-reducing bacterium Bacillus sp. SF-1.
AB  - In order to develop a biological process for removal of selenium from industrial
      wastewater, Bacillus sp. strain SF-1 was isolated from selenium-contaminated
      sediment. The bacterium reduces selenate to selenite and subsequently to nontoxic
      insoluble elemental selenium using lactate as an electron donor and selenate as
      an electron acceptor in an anaerobic condition. Elemental selenium transformed
      from soluble selenium was deposited both inside and outside of the cells. Since
      the selenate reduction rate of the strain SF-1 was higher than the selenite
      reduction rate, selenite was transiently accumulated. In an experiment of the
      repeated soluble selenium reduction by strain SF-1, 0.5 mM of selenate was
      sequentially treatable with a cycle of one day. Thus, our sequential system for
      removal of soluble selenium is very useful.

PMID- 11568464
TI  - An overview of neurolaw for the clinician: what every potential witness should
      know.
AB  - This article reviews the field of medical jurisprudence known as neurolaw which
      deals with the medicolegal ramifications of brain and spinal cord injuries.
      Placing emphasis upon how clinicians may work effectively with trial lawyers, it
      provides practical guidance to neurorehabilitation professionals who testify in
      personal injury cases.

PMID- 11568465
TI  - Neurolitigation: a perspective on the elements of expert testimony for extending
      the Daubert challenge.
AB  - Scientific expert witness testimony has the potential for affecting most court
      decisions in civil and criminal proceedings. Since experts were first utilized in
      English courts beginning in the 14th century, most contemporary courts struggle
      with seeking a balance between plaintiff and defense counsel allowing each party
      its day in court while taking into account the work which other courts have done
      previously in determining the admissibility of expert witness testimony. When
      these challenges present themselves in the courtroom, often other courts have
      approached these identical issues, many in proceedings involving the same
      expert(s). Confronted with these challenges, trial judges want to understand
      whether a new Daubert hearing must be held, deal with the issue from a clean
      slate approach or whether they must reinvent the proverbial wheel. Given these
      dilemmas, this exposition is based within a heuristic approach that will focus on
      the consideration of comprehensive data inclusion from an evidentiary foundation
      as it applies to expert witness testimony admissibility in neurolitigation. While
      the evidential force of FRE 702 specifically applies to admissibility of
      scientific evidence, it makes sense that along with scientific, objective data,
      inclusion of non-medical and other data in forming and admitting expert opinions,
      have mutual bearing upon the validity of opinions arrived at through
      neuropsychological assessment. It is these multi-data that should be factored
      into account when applying the Federal Rule of Evidence 702 scientific
      admissibility standard. Data from other relevant sources is just as vital as data
      obtained from objective measures, and co-exists with objective data. Without the
      integration of this information into resulting diagnostic data and opinions,
      one's methodology is open to scrutiny and can willfully be characterized as
      engaging in "junk science". Specific, pragmatic issues are discussed in order to
      avoid the plausible "junk science" question and to ultimately arrive at a factual
      and evidenced-based admissibility and reliability determination for the courts.
      Given the current standard, this article proposes an inclusionary method in
      neurolitigation as it would necessarily apply to Federal Rule of Evidence 702
      which would extend to the integration of data outside medical and scientific
      information bases to establish accurate opinions for the trier of fact. In so
      doing, neuropsychological test data, non-medical data and expert testimony would
      be strengthened through inter-data consistency.

PMID- 11568466
TI  - Medicolegal applications of PET scans.
AB  - Courts will allow doctors to testify about the results of PET scans only if
      doctors provide proper legal foundation for their opinions. Doctors must document
      that they have used proper scientific techniques in performing the scan. They
      must also be prepared to explain why PET scans are scientifically reliable when
      used on patients with mild traumatic brain injury (TBI).

PMID- 11568467
TI  - Admissibility of neuropsychological testimony after Daubert and Kumho.
AB  - Neuropsychological testing has been used in court cases all over the United
      States, as testimony to provide evidence of whether or not a person has a
      traumatic brain injury. It has, however, been scrutinized for its admissibility
      in court, but recognized for objectivity in successfully documenting and proving
      deficits in people with traumatic brain injuries. The trial court is used as a
      gatekeeper, and may chose to perform assessments of the tests themselves, for
      validity of sensitivity, specificity, reliability and validity in determining
      whether a neuropsychological test may be used as testimony in a court case.

PMID- 11568468
TI  - Neurolitigation of the MTBI case without loss of consciousness: using somatic
      complaints to make your case.
AB  - In court lay juries, not medical specialists in the rehabilitation of patients
      with MTBI, decide whether the plaintiff's alleged suffering and disability are
      real or fake, and if they resulted from cranio-cerebral trauma or from another
      cause for which the defendant is not responsible. This article looks at the
      ingrained bias of jurors against accepting that a person was brain injured if he
      did not suffer LOC and has a negative CT/MRI. It suggests ways of using somatic
      complaints causally associated with concussion in the absence of LOC or positive
      neuroimaging, to help MTBI patients obtain the compensation they deserve and need
      for neurorehabilitation.

PMID- 11568469
TI  - Not just malingering: syndrome diagnosis in traumatic brain injury litigation.
AB  - When patients present with syndromes we mistrust or misunderstand, clinician are
      often quick to make a determination of malingering. However, the use of
      malingering as a default diagnosis neglects a variety of clinical possibilities
      that may be relevant for treatment and forensic disposition. In neuropsychology,
      the growing use of a malingering diagnosis has recently been fueled by the
      increasingly adversarial nature of forensic brain injury litigation in which the
      goal is often less to provide an objective evaluation of cognition and
      personality as to brand all personal injury claimants as manipulative frauds.
      Less maliciously, but still disturbing, neuropsychologists whose knowledge base
      and clinical experience involves mainly the administration and scoring of
      psychometric tests may ignorantly, if innocently, overlook alternative diagnoses
      and syndromes that their education and training have ill-prepared them to
      recognize. And some patients do indeed malinger, and it is important to identify
      them, if only to spare legitimately injured claimants from being tarred with the
      same brush. This paper describes some of the syndromes that may present in
      clinical and forensic practice with brain-injured patients. It is to be
      considered a first step toward a practice model of neuropsychology that
      encourages the role of knowledge and clinical judgement in guiding the meaningful
      clinical interpretation of tests and measures.

PMID- 11568470
TI  - The roles of experts and litigation support consultants in medical-legal claims.
AB  - Brain injury claims frequently involve the use of experts to evaluate and
      document extent of impairment. These experts can cover a wide array of
      specialities, many of which are delineated in this article. It is pointed out
      that there are crucial differences between a clinical evaluation and a medical
      legal evaluation as the latter is generally more comprehensive and addresses many
      of the specific issues that arise in a forensic claim. It is suggested that use
      of a litigation support consultant can provide valuable assistance for the
      attorney at the outset and over the course of handling a claim such as with
      selection of experts and preparation for direct and cross examination of experts.
      Suggestions are also made about criteria for selection of experts such as to
      ensure that appropriate objectivity, and, consequently, admissibility of
      conclusions is maintained.

PMID- 11568471
TI  - Tuberous sclerosis complex: a Drosophila connection.

PMID- 11568472
TI  - Why are chillies pungent?

PMID- 11568473
TI  - New vistas for developmental biology.

PMID- 11568474
TI  - Controversy in science.

PMID- 11568475
TI  - Is DNA a nonlinear dynamical system where solitary conformational waves are
      possible?
AB  - DNA is considered as a nonlinear dynamical system in which solitary
      conformational waves can be excited. The history of the approach, the main
      results, and arguments in favour and against are presented. Perspectives are
      discussed pertaining to studies of DNA's nonlinear properties.

PMID- 11568476
TI  - Cloning, sequencing and expression of cDNA encoding growth hormone from Indian
      catfish (Heteropneustes fossilis).
AB  - A tissue-specific cDNA library was constructed using polyA+ RNA from pituitary
      glands of the Indian catfish Heteropneustes fossilis (Bloch) and a cDNA clone
      encoding growth hormone (GH) was isolated. Using polymerase chain reaction (PCR)
      primers representing the conserved regions of fish GH sequences the 3' region of
      catfish GH cDNA (540 bp) was cloned by random amplification of cDNA ends and the
      clone was used as a probe to isolate recombinant phages carrying the full-length
      cDNA sequence. The full-length cDNA clone is 1132 bp in length, coding for an
      open reading frame (ORF) of 603 bp; the reading frame encodes a putative
      polypeptide of 200 amino acids including the signal sequence of 22 amino acids.
      The 5' and 3' untranslated regions of the cDNA are 58 bp and 456 bp long,
      respectively. The predicted amino acid sequence of H. fossils GH shared 98%
      homology with other catfishes. Mature GH protein was efficiently expressed in
      bacterial and zebrafish systems using appropriate expression vectors. The
      successful expression of the cloned GH cDNA of catfish confirms the functional
      viability of the clone.

PMID- 11568477
TI  - Evidence for clustered mannose as a new ligand for hyaluronan- binding protein
      (HABP1) from human fibroblasts.
AB  - We have earlier reported that overexpression of the gene encoding human
      hyaluronan-binding protein (HABP1) is functionally active, as it binds
      specifically with hyaluronan (HA). In this communication, we confirm the collapse
      of the filamentous and branched structure of HA by interaction with increasing
      concentrations of recombinant-HABP1 (rHABP1). HA is the reported ligand of
      rHABP1. Here, we show the affinity of rHABP1 towards D-mannosylated albumin (DMA)
      by overlay assay and purification using a DMA affinity column. Our data suggests
      that DMA is another ligand for HABP1. Furthermore, we have observed that DMA
      inhibits the binding of HA in a concentration-dependent manner, suggesting its
      multiligand affinity amongst carbohydrates. rHABP1 shows differential affinity
      towards HA and DMA which depends on pH and ionic strength. These data suggest
      that affinity of rHABP1 towards different ligands is regulated by the
      microenvironment.

PMID- 11568478
TI  - Specificity of drug transport mediated by CaMDR1: a major facilitator of Candida
      albicans.
AB  - CaMDR1 encodes a major facilitator superfamily (MFS) protein in Candida albicans
      whose expression has been linked to azole resistance and which is frequently
      encountered in this human pathogenic yeast. In this report we have overexpressed
      CaMdr1p in Sf9 insect cells and demonstrated for the first time that it can
      mediate methotrexate (MTX) and fluconazole (FLC) transport. MTX appeared to be a
      better substrate for CaMdr1p among these two tested drugs. Due to severe toxicity
      of these drugs to insect cells, further characterization of CaMdr1p as a drug
      transporter could not be done with this system. Therefore, as an alternative,
      CaMdr1p and Cdr1p, which is an ABC protein (ATP binding cassette) also involved
      in azole resistance in C. albicans, were independently expressed in a common
      hypersensitive host JG436 of Saccharomyces cerevisiae. This allowed a better
      comparison between the functionality of the two export pumps. We observed that
      while both FLC and MTX are effluxed by CaMdr1p, MTX appeared to be a poor
      substrate for Cdr1p. JG436 cells expressing Cdr1p thus conferred resistance to
      other antifungal drugs but remained hypersensitive to MTX. Since MTX is
      preferentially transported by CaMdr1p, it can be used for studying the function
      of this MFS protein.

PMID- 11568479
TI  - Insulin alone can lead to a withdrawal of meiotic arrest in the carp oocyte.
AB  - Meiotic arrest of oocyte in an Indian carp, Labeo rohita Ham. has been found for
      the first time to be withdrawn by insulin only. Addition of insulin to oocytes in
      vitro caused germinal vesicle breakdown (GVBD), one of the first visual markers
      to determine initiation of the final maturational process. Under the influence of
      insulin the germinal vesicle (GV) of the oocyte migrated towards the animal pole,
      reached the micropyle and then dissolved (GVBD). By using different
      concentrations of insulin i.e., 0.063, 0.63, 6.3 and 12.6 mM, optimum amount
      required was found to be 6.3 mM. Induction of GVBD by insulin could be blocked by
      cycloheximide (Chx), a translation inhibitor, while actinomycin D (AcD) had no
      effect suggesting non-involvement of transcriptional activity in this process.
      Addition of the maturation-inducing steroid 17alpha,20beta-dihydroxy-4-pregnen-3
      one (DHP) stimulated (P<0.01) GVBD of carp oocytes and its combination with
      insulin showed an additive effect. Gonadotropin (GtH) caused GVBD but its effect
      was greatly augmented by insulin. Our results demonstrate that not only can
      insulin alone induce GVBD in carp oocytes, but it also augments the stimulatory
      effect of DHP or IGF-I or GtH on GVBD. This information will be important in
      hormonal manipulation during induced breeding of carp.

PMID- 11568480
TI  - Pancreatic islet-cell viability, functionality and oxidative status remain
      unaffected at pharmacological concentrations of commonly used antibiotics in
      vitro.
AB  - Environmental factors such as diet, physical activity, drugs, pollution and life
      style play an important role in the progression and/or precipitation of diseases
      like diabetes, hypertension, obesity and cardiovascular disorders. Indiscriminate
      use of antibiotics to combat infectious diseases is one of the commonest forms of
      misuse of drugs. Antibiotics seem to have a correlation with diabetes and
      pancreatic function. There are controversial reports about the effect of
      antibiotics on the pancreatic islets; some suggesting their harmless action, some
      depicting a beneficial role and others indicating deleterious effect. Moreover,
      use of antibiotics is mandatory during islet isolation and cultivation to reduce
      incidences of microbial contamination. It is likely that antibiotic treatment may
      adversely affect islet viability and its functioning leading to failure of islet
      transplantation. The present in vitro study was undertaken to examine the effect
      of commonly used antibiotics such as gentamycin, penicillin, streptomycin,
      tetracycline, neomycin, erythromycin and chloramphenicol on islet viability, its
      functioning and induction of oxidative stress if any. The viability and insulin
      production data showed that none of the antibiotics used in the present study
      affect the viability and the functioning of the islets at their pharmacological
      concentrations. Free radical levels measured in terms of melonyldialdehyde (MDA),
      nitric oxide (NO) and reduced glutathione (GSH) reveal that except for a marginal
      increase in lipid peroxidation with tetracycline and slight increase in NO levels
      with streptomycin, none of these antibiotics affect the oxidative status of the
      cells. Antioxidant enzymes such as superoxide dismutase and catalase remain
      unaffected after this treatment. Our results reveal the innocuous nature of the
      antibiotics used at pharmacological concentrations, suggesting their safety
      whenever prescribed to combat infections and also during islet isolation
      procedures.

PMID- 11568481
TI  - Calcium - how and why?
AB  - Calcium is among the most commonly used ions, in a multitude of biological
      functions, so much so that it is impossible to imagine life without calcium. In
      this article I have attempted to address the question as to how calcium has
      achieved this status with a brief mention of the history of calcium research in
      biology. It appears that during the origin and early evolution of life the Ca2+
      ion was given a unique opportunity to be used in several biological processes
      because of its unusual physical and chemical properties.

PMID- 11568482
TI  - Incipient sexual isolation in the nasuta-albomicans complex of Drosophila: mating
      preference in male-, female- and multiple-choice mating experiments.
AB  - Interracial divergence is an important facet of speciation. The nasuta-albomicans
      complex of Drosophila with sixteen morphologically identical, karyotypically
      different but cross-fertile races is an excellent system to study a few
      dimensions of raciation. Drosophila nasuta nasuta, Drosophila nasuta albomicans,
      Cytorace 1, Cytorace 2, Cytorace 3 and Cytorace 4 of this subgroup have been
      subjected to male-, female- and multiple-choice mating experiments. Out of 8456
      crosses conducted, 7185 had successful matings. The overall impression is that
      mating is far from random amongst these six closely related races of the nasuta
      albomicans complex. The males of D. n. albomicans, Cytorace 1 and Cytorace 4 in
      male-choice, the females of Cytorace 1 and Cytorace 2 in female-choice, and the
      males and females of D. n. nasuta, D. n. albomicans, Cytorace 1 and Cytorace 4
      against the males and females of Cytorace 2 in multiple-choice experiments, had
      significantly more homogamic matings than expected. Thus in this study of
      evolutionary experimentation on raciation under laboratory conditions, we have
      documented the initiation of preference for conspecific matings among closely
      related and independently evolving members of the nasuta-albomicans complex of
      Drosophila.

PMID- 11568483
TI  - Effects of water level changes and wading bird abundance on the foraging
      behaviour of blacknecked storks Ephippiorhynchus asiaticus in Dudwa National
      Park, India.
AB  - The effect of water level changes and wading birds' abundance on the foraging
      behaviour of the blacknecked stork (BNS) Ephippiorhynchus asiaticus was studied
      from January 1995 to June 1997 in Dudwa National Park, Uttar Pradesh. Our
      observations indicate that BNS territoriality increased as food levels became
      depleted, resulting in increased rates of aggression towards intruders. Chasing
      or aggression was more intense during the early period (February and March) than
      the late period (April, May and June). Most of (> 50%) the aggressive encounters
      were observed between 0600 and 1000 h of the day. Seventeen species (including
      BNS) were observed interacting with BNS, throughout the study period. Most
      interactions were with the spoonbill, Platalea leucorodia (67.4%), followed by
      the whitenecked stork, Ciconia episcopus (16.6%). The distance (while foraging)
      between BNS and other wading birds varied significantly (P < 0.001) between years
      indicating that BNS and other water birds foraged at different water depths and
      thereby explored the wetlands fully. Spoonbills were chased often; the number
      varied from 1 to 43 birds. BNS occasionally accepted the presence of other wading
      birds, including spoonbills and started foraging amidst them. This led to
      successful foraging of BNS (solitary feeder). Other fish-eating bird species and
      their numbers also limited the food consumption of foraging BNS as they had to
      spend time chasing away the intruders. Availability of the preferred prey fish
      species, Heteropnestus fossilis, forced BNS to stay throughout the year in their
      respective territories. High (> 60 cm) water levels were not suitable for BNS
      even though the patch had high prey abundance.

PMID- 11568485
TI  - The ideal prepuce in ancient Greece and Rome: male genital aesthetics and their
      relation to lipodermos, circumcision, foreskin restoration, and the kynodesme.
AB  - This study examines the evolution of Greek and Roman medical conceptualizations
      of preputial aesthetics, utilizing evidence found in classical medical texts as
      well as clues from literature, legal sources, and art. A conclusive picture
      emerges that the Greeks valued the longer prepuce and pathologized the penis
      characterized by a deficient prepuce--especially one that had been surgically
      ablated--under the disease concept of lipodermos. The medical conceptualization
      of lipodermos is also placed in the historical context of the legal efforts to
      abolish ritual circumcision throughout the Seleucid and Roman empires.

PMID- 11568484
TI  - Orally active insulin mimics: where do we stand now?
AB  - The war against diabetes through the development of new drugs is an ongoing
      continuous process to counter the alarming global increase in the prevalence of
      diabetes and its complications, particularly in developing countries like India.
      Unfortunately, the speed with which our knowledge of diabetes and its effects is
      expanding is not matched by the availability of new drugs. Following the
      identification of the insulin receptor (IR), its intrinsic kinase activity and
      molecular cloning, many studies have looked at IR as an ideal drug target. This
      review summarizes in brief the latest advancements in this field with particular
      reference to the current situation in respect of the development of orally active
      insulin mimetics in the treatment of type 2 diabetes.

PMID- 11568486
TI  - Insurance against germ theory: commerce and conservatism in late-Victorian
      medicine.
AB  - This article highlights the role played by commercial life insurance companies in
      determining the response to tuberculosis in Britain between 1865 and 1920. Late
      Victorian life offices hired two sorts of physicians to help them screen out high
      risk proposals: provincial medical examiners, who collected fees for examining
      candidates; and salaried medical advisors, who developed guidelines for the
      medical examination and interpreted the examiners' findings for the head office.
      The latter set of physicians, many of whom worked at specialist consumption
      hospitals in London, established an orthodoxy among life offices that privileged
      hereditarian explanations for the cause of tuberculosis. The provincial examiners
      resisted that orthodoxy, arguing that advances in public health and treatment
      rendered irrelevant any apparent correlation between family history and
      tuberculosis. In adjudicating this internal dispute, life offices stood by their
      salaried advisors, but in the process pushed them away from viewing disease in
      terms of specific causes and toward viewing disease in terms of statistical
      correlation. This victory of statistics over etiology preserved, at least for the
      rest of the twentieth century, the institutional prominence of insurance as a
      technique for coping with medical uncertainty.

PMID- 11568487
TI  - Healthy public relations: the FDA's 1930s legislative campaign.
AB  - In this article, I argue that the Food and Drug Administration (FDA) is an oft
      overlooked government agency that acts to preserve and secure the public's
      health. From its early years as an agency charged with enforcement of the 1906
      Pure Food and Drugs Act, the FDA not only protected the public's health but also
      made the public aware of its mission, using methods as diverse as displays at
      county fairs and at the 1933 Chicago World's Fair, radio programming, and active
      correspondence. The agency encouraged the public to protect itself, particularly
      in those arenas in which the FDA had no regulatory authority. In addition, it may
      have overstepped its boundaries when it actively solicited public support for a
      bill submitted to Congress in the early 1930s. In the dark days of the Great
      Depression, the FDA contended not only with limited resources and its own
      feelings of inadequacy in terms of what could and could not be done to protect
      the populace, but also with "guinea pig" books that horrified and angered many
      readers. By 1938, when the agency prevailed and the revisions to the 1906 Act
      passed Congress and were signed into law by President Franklin D. Roosevelt, the
      FDA had done all that a responsible public health agency should do, and more.

PMID- 11568488
TI  - The polio narratives: dialogues with FDR.
AB  - As a group of accounts that span the decades from the mid-1940s to the present,
      the published polio narratives enable us to align their shifting perceptions of
      disability with social, cultural, and technological change. This paper identifies
      two distinct groups of narratives. Authors of the first group, writing between
      the mid-1930s and mid-1950s--a period of relative prosperity, conformity, and
      homogeneity--were uncomfortable with radical movements, diversity, and conflict;
      their narratives typically told of either full or substantial recovery. Beginning
      in the mid-1950s--the period of both McCarthy and the Civil Rights movement--a
      second wave of narratives begins to tell stories of partial to serious
      disability; typically, they reflect on a lifetime of coping with chronic
      disability. Both sets of narratives, however, represent a dialogue with Franklin
      Delano Roosevelt. Roosevelt himself, journalists, and the National Foundation for
      Infantile Paralysis all helped to create and promote a core polio narrative
      featuring FDR's triumph over disease and disability that would become a national
      myth. Yet while the early narratives reinforced the core elements of the
      Roosevelt myth, the later ones began to challenge them.

PMID- 11568493
TI  - Why don't they read our literature?

PMID- 11568494
TI  - Methods of assessing stability of parenteral nutrition regimens.
AB  - Increased use of intravenous in-line filtration for all-in-one admixtures has
      been one of several recent stimuli to developing methods for assessing the
      stability of parenteral nutrition regimens. Admixture formulations previously
      deemed to be 'stable' have caused filter blockage and this requires urgent
      reconsideration of the definitions of physical emulsion stability. The new
      technique of acoustic attenuation spectroscopy has been evaluated as another
      means of assessing physical stability of emulsions, and some of the newer
      techniques have been further applied to provide additional insight into the
      effects of light and oxygen. There has also been additional work on trace element
      contamination and changes in trace element concentrations on storage. Overall
      this review period has been one of evolution rather than revolution.

PMID- 11568495
TI  - Advances in methods to evaluate gastrointestinal transport function.
AB  - Malnutrition is a serious problem, and malabsorption of nutrients is believed to
      be partially responsible for its prevalence. A wide variety of innovative methods
      have been developed to study gastrointestinal transport function. Some of the
      first research into gastrointestinal function was conducted in the 1700's with
      animal and human models. Methodological advancements continue to allow scientists
      to innovatively assess gastrointestinal function in animal models, cellular
      preparations and clinical settings. For this update, the methods are divided into
      in vivo, ex vivo, isolated cells and membranes, and molecular biology approaches.
      The in vivo methods discussed include animal and human models to measure nutrient
      disappearance, catheterized animal models, models with isolated intestinal
      segments, and a new procedure for sampling luminal fluid from patients. The ex
      vivo approaches discussed obtain measurements with intact tissue, such as the
      everted sleeves method and Ussing chambers. The utility of novel cellular
      preparations, membrane fractionation procedures and various molecular biology
      techniques is included. Various aspects of these methods are evaluated to provide
      a detailed overview of recent methodological developments.

PMID- 11568496
TI  - Methods for assessing intestinal absorptive function in relation to enteral
      nutrition.
AB  - The success of nasoenteral nutrition support can be limited by intestinal
      impairment. In particular, reduced absorptive area, mucosal atrophy and abnormal
      motility may reduce absorption of macronutrients and micronutrients, and
      diarrhoea remains a commonly encountered complication. We review how basic
      physiological techniques can be used to investigate such pathophysiology. Lumenal
      nutrients control mucosal growth, expression of mucosal transporters and regional
      gut motility. Cell biology techniques now complement classical intestinal
      perfusion methods in determining the 'safety factor' of excess absorptive
      capacity. The controversial role of the sodium-glucose linked transporter in
      dietary glucose assimilation is described in terms of its control, its true
      function and its role in uptake of other solutes. Techniques that involve brush
      border membrane vesicles, Caco-2 cells, mucosal immunohistochemistry and gene
      expression probes are described. Together, these techniques describe a picture of
      an organ with remarkable ability to maintain digestive and absorptive function in
      response to a wide variety of nutritional intakes, often in the face of
      inflammatory illness.

PMID- 11568497
TI  - Proteomics: analytical tools and techniques.
AB  - Scientists have long been interested in measuring the effects of different
      stimuli on protein expression and metabolism. Analytical methods are being
      developed for the automated separation, identification, and quantitation of all
      of the proteins within the cell. Soon, investigators will be able to observe the
      effects of an experiment on every protein (as opposed to a selected few). This
      review presents a discussion of recent technological advances in proteomics in
      addition to exploring current methodological limitations.

PMID- 11568498
TI  - Differences in body-composition assumptions across ethnic groups: practical
      consequences.
AB  - Body-composition methodologies rely on assumptions that are not constant across
      ethnic groups. The consequence is that the methods used need to be population
      specific to guarantee unbiased conclusions. Alternatively, assumption-free
      methods such as chemical multiple-compartment models or scanning techniques
      should be used. Adequate and unbiased scientific data on body fat among ethnic
      population groups are necessary for a better understanding of the aetiology of
      obesity and its co-morbidities. The World Health Organization cut-off points for
      underweight, overweight, obesity and fat distribution, now universally defined,
      may need revision because the relationship between body mass index and body
      composition, and between indices of fat distribution and the actual amount of
      visceral fat, differ across ethnic groups. The need for ethnically specific cut
      off points for obesity and fat distribution is substantiated, for example, by
      elevated disease risks at low levels of body mass index in several populations.
      Properly designed and conducted studies are needed to obtain unbiased information
      on these topics.

PMID- 11568499
TI  - Clinical role of polyamine analysis: problem and promise.
AB  - Polyamines are ubiquitous cell components for growth. They play an important role
      in cell proliferation, cell growth and synthesis of protein and nucleic acids.
      Cells that are stimulated to reproduce demonstrated early increases in
      biosynthetic enzymes involved in polyamine synthesis and subsequent elevations in
      polyamine levels. Extracellular fluid polyamine concentrations that reflect the
      intracellular events may be useful as rapid indicators of therapy in disorders
      which involve altered cell growth. More complex analytical approaches are
      required to isolate, identify and quantitate these polyamines. Most of the
      methods require an extraction procedure to remove interfering amino acid
      derivatives. Daily monitoring of plasma and urine polyamine levels in many
      pathological states may provide a non-invasive biochemical marker of the existing
      disease activity or response to therapy or to screen for drug efficacy. Automated
      high-performance liquid chromatography, with post or pre-column derivatization
      and fluorescence or electrochemical detection is frequently used for the
      simultaneous quantitation of picomolar quantities of polyamines. Recently, a new
      immuno-cytochemical model system incorporating an enzyme-linked immunosorbent
      assay for specific polyamines has been developed. The increasing momentum of
      basic science information in the polyamine discipline may lead clinicians to
      regard polyamines, their metabolites and antimetabolites as sources of effective
      treatment.

PMID- 11568500
TI  - Comparing energy expenditure data among individuals differing in body size and
      composition: statistical and physiological considerations.
AB  - Acute and chronic diseases are frequently characterized by alterations in energy
      metabolism that influence nutritional requirements and clinical care. Knowledge
      of the effect of disease on daily energy expenditure and its components is
      fundamental to understanding the impact of the disease process on energy balance.
      To obtain this information, energy expenditure data are often compared between
      healthy and diseased individuals. This review focuses on the statistical and
      physiological issues related to comparing energy expenditure data among
      individuals who differ in body size and composition.

PMID- 11568501
TI  - Utility of insulin-like growth factor-I and its binding protein assays.
AB  - Insulin-like growth factor-I circulates in serum either in free form or bound to
      insulin-like growth factor-binding proteins that modulate its bioavailability.
      Insulin-like growth factor-binding proteins interfere with insulin-like growth
      factor-I assay, which remains technically difficult. Many assays have been
      developed, but their results are somewhat discordant. The choice of separation
      method, standard and tracer considerably influences the results. The circulating
      concentration of insulin-like growth factor-I, however, is clearly dependent on
      nutritional status, and total levels are a valuable marker of nutritional status.
      The clinical utility of free insulin-like growth factor-I assay and simultaneous
      assay, in the same sample, of total insulin-like growth factor-I and its binding
      proteins (reflecting the bioavailable insulin-like growth factor-I fraction),
      remains to be evaluated.

PMID- 11568502
TI  - The gene-nutrient-gene loop.
AB  - It is increasingly apparent that the genetic influence on the development and
      severity of a particular phenotype (e.g. diabetes, hyperlipidemia, hypertension,
      and coronary heart disease) can be strongly modulated by diet. In turn, the
      response of the phenotype to dietary intervention is determined by the individual
      genotype. The reviews in this issue provide striking examples of recent progress
      related to the molecular basis of nutrient-gene interactions. As our
      understanding of these interactions improves, we should be better equipped to
      identify individuals at risk of specific pathologies and make a better assessment
      of the risk involved. Nutritional support could then be tailored to the
      individual genotype to favour beneficial phenotypic expression or to suppress
      that leading to pathology and disease.

PMID- 11568503
TI  - 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: suiting structure to need,
      in a family of tissue-specific enzymes.
AB  - The present review addresses recent advances in research into a family of
      bifunctional enzymes that are responsible for the twofold task of synthesizing
      and hydrolyzing fructose-2,6-bisphosphate (Fru-2,6-P2), which in turn regulates
      the rate of glycolysis in most cells. The structure of the synthetic kinase,
      conjoined at its carboxyl-terminus to the phosphatase, is very highly conserved
      throughout evolution and differentiation, with isotypic expression arising from
      highly variable amino-terminal and carboxyl-terminal regulatory domains. These
      domains, which frequently contain protein-kinase-catalyzed phosphorylation
      motifs, are responsible for the widely divergent kinetics observed in various
      tissues and species, and for the hormonal modulation that alters intracellular
      levels of Fru-2,6-P2. The present review discusses recent advances in relating
      structure to function, and the identification of new pathways of transcriptional
      regulation of this important family of regulatory enzymes.

PMID- 11568504
TI  - Regulation of branched-chain amino acid catabolism: nutritional and hormonal
      regulation of activity and expression of the branched-chain alpha-keto acid
      dehydrogenase kinase.
AB  - Branched-chain alpha-keto acid dehydrogenase kinase is responsible for the
      inactivation and phosphorylation of the branched-chain alpha-keto acid
      dehydrogenase complex, the enzyme that catalyses the committed step of branched
      chain amino acid catabolism. The activity of the branched-chain alpha-keto acid
      dehydrogenase complex is inversely correlated with kinase activity, suggesting
      that the relative activity of the kinase is the primary regulator of the activity
      of the complex. It has been shown that kinase activity and expression are
      affected by nutritional states imposed by low-protein diet feeding, starvation,
      diabetes, and exercise. Evidence has also been presented that certain hormones,
      particularly insulin, glucocorticoid, thyroid hormone and female sex hormones,
      affect the activity and expression of the kinase. The findings indicate that
      nutritional and hormonal control of the activity and expression of branched-chain
      alpha-keto acid dehydrogenase kinase provides an important means of control of
      the activity of the branched-chain alpha-keto acid dehydrogenase complex, with
      inactivation serving to conserve branched-chain amino acids for protein synthesis
      in some situations and activation serving to provide carbon for gluconeogenesis
      in others.

PMID- 11568505
TI  - Regulation of amino acid transporters by amino acid availability.
AB  - There is growing recognition that amino acid availability has profound effects on
      many aspects of cell function, including the control of membrane transport
      mechanisms, cell signalling, and gene expression. The precise mechanisms by which
      amino acids are able to elicit control over such diverse processes have become
      the focus of intense investigation recently. One particular area that has seen
      considerable advances is the molecular characterization of amino acid
      transporters, including members of the System A family, which are known to be
      regulated by amino acid supply. Recent developments concerning how cells sense
      and signal amino acid availability, and how this process influences the
      expression and function of amino acid transporters, are reviewed here.
      Elucidating the molecular mechanisms of these events will be important in
      clarifying how amino acid transporters might be regulated during altered
      nutritional states, and will be crucial for the design of new strategies aimed at
      improving nutritional support.

PMID- 11568506
TI  - Fatty acid regulation of gene expression.
AB  - Over the past 10 years it has become evident that fatty acids regulate cellular
      functions by modulating gene expression. Fatty acids and fatty acid metabolites
      exert some of their effects on gene expression by affecting the activity of
      nuclear transcription factors, peroxisome proliferator-activated receptors and
      sterol regulatory element binding protein type 1. The present review describes
      the latest developments in the field, with particular emphasis on the
      physiological roles of the various peroxisome proliferator-activated receptor
      isotypes, including their implication in the control of proliferation and
      differentiation of normal and malignant cells, and on the mechanisms implicated
      in the regulation of sterol regulatory element binding protein type 1 activity by
      polyunsaturated fatty acids.

PMID- 11568507
TI  - Recent advances on molecular mechanisms involved in amino acid control of gene
      expression.
AB  - In mammals, the impact of nutrients on gene expression has become an important
      area of research. Because amino acids have multiple and important functions,
      their homeostasis has to be finely maintained. However, amino acidaemia can be
      affected by certain nutritional conditions or various forms of aggression. It
      follows that mammals have to adjust several of their physiological functions
      involved in the adaptation to amino acid availability by regulating the
      expression of numerous genes. It has been shown that amino acids by themselves
      can modify the expression of target genes. However, the current understanding of
      amino acid-dependent control of gene expression has just started to emerge. This
      review focuses on the recent advances on mechanisms involved in the amino acids
      control of gene expression. Several examples discussed in this paper demonstrate
      that amino acids regulate gene expression at the level of transcription,
      messenger RNA stability and translation.

PMID- 11568508
TI  - Phytoestrogens: the pediatric perspective.

PMID- 11568509
TI  - Monogenic disorders that cause LDL cholesterol to accumulate in plasma.

PMID- 11568510
TI  - Apolipoprotein B Arg3500Gln mutation prevalence in children with
      hypercholesterolemia: a French multicenter study.
AB  - BACKGROUND: Familial defective apolipoprotein B-100, a dominantly inherited form
      of hypercholesterolemia caused by a single Arg3500Gln mutation, is silent in
      childhood but may confer a high risk of cardiovascular disease in adulthood. The
      objective was to determine the prevalence of familial defective apolipoprotein B
      100 in hypercholesterolemic French children and to provide a basis for targeting
      screening efforts in this population. METHODS: One hundred ninety children
      attending 13 pediatric clinics distributed throughout France were included based
      on the presence of type IIa hypercholesterolemia with a plasma low-density
      lipoprotein-cholesterol level of more than 130 mg/dL. The Arg3500Gln mutation was
      detected in dried blood spots using a polymerase chain reaction assay combined
      with enzymatic restriction. RESULTS: Three hyperlipidemia phenotypes were found:
      monogenic dominant pure hypercholesterolemia (n = 117), polygenic
      hypercholesterolemia (n = 43), and combined hyperlipidemia (n = 11). Three
      unrelated children were heterozygous for the Arg3500Gln mutation; all three had
      monogenic dominant pure hypercholesterolemia (3/94 families; 3.2%), yielding a
      prevalence of 1.83% (3/164) in hypercholesterolemic children, which is similar to
      prevalences reported in European adults. CONCLUSIONS: The familial defective
      apolipoprotein B-100 mutation was common (1/31) in children with a phenotype of
      familial hypercholesterolemia, supporting screening in this population with the
      goal of preventing premature cardiovascular events.

PMID- 11568511
TI  - Proinflammatory cytokine expression in gastric tissue from children with
      Helicobacter pylori-associated gastritis.
AB  - BACKGROUND: Helicobacter pyloriinfection of the gastric mucosa in humans is
      usually acquired early in life. The chronic inflammation that ensues involves the
      increased production of inflammatory cytokines. Published data on production of
      these mediators by gastric mucosa of H. pylori-infected children are few.
      METHODS: Seventy-nine children, aged 5 to 18 years, referred for upper
      gastrointestinal endoscopy to four separate hospitals in Chile, were studied. The
      concentrations of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor
      alpha were measured in homogenates of gastric mucosal biopsy specimens. Cytokine
      expression was confirmed by reverse transcription polymerase chain reaction.
      These data were correlated with the patients' clinical, histologic and
      sociodemographic status. RESULTS: Patient rate of colonization by H. pylori was
      inversely correlated with socioeconomic status (P < 0.005) and positively
      correlated with age (P < 0.0025). In gastric mucosa, concentrations of IL-1beta,
      IL-8, and tumor necrosis factor alpha were all significantly higher in H. pylori
      positive patients than in H. pylori-negative patients and in patients who had
      histologic gastritis than in those with normal gastric mucosa. In patients with
      peptic ulcer disease, only IL-1beta and IL-8 concentrations were significantly
      elevated when compared with those of patients without ulcers. Interleukin-6
      concentrations were comparable among the different groups analyzed. CONCLUSIONS:
      This study suggests that increased gastric mucosal production of the
      proinflammatory cytokines IL-1beta and IL-8 is probably involved in H. pylori
      associated gastric damage in children and may be crucial in determining the
      different clinical outcomes.

PMID- 11568512
TI  - T cells of the colonic mucosa in patients with infantile colitis.
AB  - BACKGROUND: Infantile colitis is a heterogeneous group of disorders, including
      enterocolitis complicating Hirschsprung disease, allergic colitis, inflammatory
      bowel disease, and Behcet syndrome. There are limited data concerning the immune
      responses induced by the inflammation of the intestine in young infants. METHODS:
      Twenty-four colonic biopsy specimens from 12 infantile colitis patients and 12
      age-matched control patients were studied by immunohistologic methods. The
      authors compared the T cells, their subsets expressing the surface antigens CD8
      and CD4, and T-cell receptors alphabeta and deltagamma, and densities of
      mononuclear and epithelial cells expressing human leukocyte antigen class II
      antigens. RESULTS: The density of CD3+ intraepithelial lymphocytes (IELs) in the
      large intestinal specimens was significantly higher (P = 0.036) in colitis
      patients than in the control group. The majority of the CD3+ IELs were CD8+
      expressing cells, and only a minority were CD4+ cells in both groups. T-cell
      receptors alphabeta+ (P = 0.023) and deltagamma+ (P = 0.027) IELs were observed
      significantly more frequently in colitis patients than in the control group. In
      surface epithelium, delta non-disulphide-linked type T-cell receptor (deltaTCS1)
      IELs were found strikingly more frequently (P = 0.001) in the specimens taken
      from the colitis patients. Also, the density of the deltaTCS1+ cells in crypts of
      the large intestine was significantly higher in colitis patients than in the
      control patients (P = 0.047). CONCLUSIONS: A significant increase of CD3+
      lymphocytes in the colonic epithelium of the patients with infantile colitis was
      noted. This increase involved both T-cell receptor alphabeta-positive and
      deltagamma-positive IELs. The finding of this study supports the proposal that
      intraluminal antigens, either microbial or food derived, are important in the
      pathogenesis of colitis in young infants.

PMID- 11568513
TI  - Prevalence and clinical picture of celiac disease in italian down syndrome
      patients: a multicenter study.
AB  - BACKGROUND: A multicenter research study of Down syndrome patients was carried
      out to estimate the prevalence of celiac disease in patients with Down syndrome
      and to show clinical characteristics and laboratory data of Down syndrome
      patients. METHODS: The authors studied 1,202 Down syndrome patients. Fifty-five
      celiac disease patients (group 1) were compared with 55 immunoglobulin A
      antigliadin-positive antiendomysium antibodies-negative patients (group 2) and
      with 57 immunoglobulin A antigliadin-negative antiendomysium antibodies-negative
      patients (group 3). RESULTS: Celiac disease was diagnosed in 55 of 1,202 Down
      syndrome patients (4.6%). In group 1, weight and height percentiles were shifted
      to the left, whereas these parameters were normally distributed in groups 2 and
      3. In celiac patients, diarrhea, vomiting, failure to thrive, anorexia,
      constipation, and abdominal distension were higher than in the other two groups.
      Low levels of hemoglobinemia, serum iron, and calcium were observed more
      frequently in group 1. The diagnosis of celiac disease was made after a mean
      period of 3.8 years from the initiation of symptoms. Sixty-nine percent of
      patients showed a classic presentation, 11% had atypical symptoms, and 20% had
      silent celiac disease. Autoimmune disorders were more frequent (30.9%) in group 1
      than in the other two groups examined (15%; P < 0.05). CONCLUSIONS: This study
      reconfirms a high prevalence of celiac disease in Down syndrome. However, the
      diagnostic delay, the detection of atypical symptoms or silent form in one third
      of the cases, and the increased incidence of autoimmune disorders suggest the
      need for the screening of celiac disease in all Down syndrome patients.

PMID- 11568514
TI  - Intravenous omeprazole in children: pharmacokinetics and effect on 24-hour
      intragastric pH.
AB  - BACKGROUND: Omeprazole is a proton pump inhibitor, acting selectively on the
      gastric parietal cell H+K+-adenosine triphosphatase. Data on the intravenous
      route are limited in children and not available in infants. OBJECTIVE: This study
      was designed to determine the pharmacokinetics and the optimal dosage of
      intravenous omeprazole in patients younger than 30 months of age. METHODS: Nine
      children (three girls), aged 4.5 to 27 months, with normal liver and renal
      functions requiring intravenous omeprazole were studied. After enrollment in the
      study and randomization, omeprazole was administered once daily, at 8 am, as a 1
      hour infusion. Group 1, consisting of the first four patients, received 20
      mg/1.73 m2, and group 2, consisting of the following five patients, received 40
      mg/1.73 m2. At day 3, a 24-hour intragastric pH and a pharmacokinetic study of
      omeprazole were performed. Plasma concentrations were measured by high
      performance liquid chromatography. RESULTS: Patients in group 2 had a
      significantly higher median pH (6.99 vs. 3.35; P = 0.01) and percent of monitored
      time with gastric pH >4 than children given 20 mg/1.73 m2 (90.6% vs. 44.8%; P <
      0.01). Four had a pH more than 4 during more than 90% of the time versus none of
      the patients of group 1. The plasma concentration versus time curves showed rapid
      elimination of the drug. The median area under the curve of omeprazole was 0.78
      microg. mL-1. h-1 (range, 0.55-1.64 microg. mL-1. h-1) and 3.95 microg. mL-1. h-1
      (range, 1.9-4.9 microg. mL-1. h-1), respectively, in groups 1 and 2 (P < 0.05).
      Systemic clearance was not different between the two groups: median values were
      0.68 and 0.42 L. kg-1. h-1 (P = 0.22). CONCLUSIONS: In critical situations,
      intravenous administration of omeprazole may be required in infants. The authors
      demonstrate that the dose of 20 mg/1.73 m2 is not effective in maintaining 24
      hour gastric pH of more than 4 and that a dose of 40 mg/1.73 m2 is required.

PMID- 11568515
TI  - Abdominal migraine in children with neurofibromatosis type 1: a case series and
      review of gastrointestinal involvement in NF1.
AB  - BACKGROUND: Symptomatic involvement of the gastrointestinal tract in children
      with neurofibromatosis type 1 (NF1) is rare. Most reported complications in
      adults are caused by the presence of neurofibromas in the stomach, small bowel,
      or mesentery. In contrast, abdominal pain in children with NF1 may be the result
      of nonanatomic causes, such as migraine. There are no previous reports of an
      association between abdominal migraine and NF1. METHODS: Children with abdominal
      migraine were identified from a group of children with NF1, all of whom had been
      followed up for a minimum of 3 years. Medical records of cases were reviewed
      independently by two authors. MEDLINE was searched via PubMed for all reports of
      children with NF1 and any associated gastrointestinal involvement. RESULTS: Six
      children with NF1 and intermittent, episodic, severe abdominal pain are reported.
      Investigations for obstructive or inflammatory causes of abdominal pain were
      negative. All patients had previously been diagnosed with migraine headaches by a
      neurologist. In five of the six patients, propranolol (10-15 mg three times
      daily) resulted in relief of their abdominal pain within days of starting
      therapy. Our review identified 24 children in the medical literature with
      gastrointestinal complications of NF1, mostly secondary to visceral
      neurofibromas. In almost all of these cases, clinical examination and simple
      radiologic investigations led to the definitive diagnosis. There were no reports
      of abdominal migraine complicating NF1. CONCLUSIONS: Abdominal pain secondary to
      migraine is an unrecognized cause of abdominal pain in children with NF1 and may
      be more common than anatomic causes of abdominal pain in children with NF1. In
      children with NF1 and severe recurrent abdominal pain in whom an evaluation for
      anatomic lesions is negative, a trial of migraine therapy may be indicated.

PMID- 11568516
TI  - Randomized, multicenter trial of two different formulas for very early enteral
      feeding advancement in extremely-low-birth-weight infants.
AB  - BACKGROUND: In extremely-low-birth-weight (ELBW) infants, formula feeding is
      required if human milk is not available. The tolerance of a new 'high' lactose
      (55 g/L), low protein, low phosphate, hydrolyzed protein formula (HLF) for early
      enteral feeding advancement of ELBW infants was compared with that of a low
      lactose (1 g/L) hydrolyzed protein formula (LLF). METHODS: In a randomized
      multicenter trial, 99 ELBW infants were fed according to a standardized protocol
      beginning at 48 hours of age with 12 ml/kg daily increments. Primary outcome was
      the cumulative milk feeding volume (CFV) from days 3 to 14. The authors
      hypothesized that feeding HLF as a supplement to human milk would increase the
      CFV at least by 20% in at least 60% of matched pairs compared with LLF. A
      secondary issue was to investigate whether human milk would increase the CFV
      compared with formula. RESULTS: The CFV was 720 mL/kg (range, 0-962 mL/kg) with
      HLF and 613 mL/kg (range, 3-1,283 mL/kg) with LLF feeding. There was no 20%
      difference. On day 14, the median feeding volume was 103 mL/kg. The CFV was 533
      mL/kg (range, 0-962 mL/kg) in infants who received less than 10% of human milk
      and 832 mL/kg (range, 74-1,283 mL/kg) in infants who received more than 10%.
      Necrotizing enterocolitis (Bell stage > or =2) occurred only with LLF feeding (n
      = 5; P < 0.05). CONCLUSIONS: The study failed to find the hypothesized 20%
      advantage of the new HLF. The observed advantage of human milk supports the
      hypothesis that it should be the first diet in ELBW infants; however, this
      hypothesis still must be confirmed in a controlled, randomized trial.

PMID- 11568517
TI  - Beta endorphin concentrations in human milk.
AB  - BACKGROUND: The source and regulatory mechanisms that elevate beta-endorphin
      (beta-EP) approximately twofold higher than circulating plasma levels in the
      colostrum of lactating mothers are still unknown, and no studies have examined
      beta-EP availability previously during maturation phases of human milk.
      Therefore, the aim of this study was to determine whether concentrations of beta
      EP vary over time between colostrum, transitional, and mature breast-milk and to
      evaluate whether this depends on the method of delivery. METHODS: Mothers of
      healthy full-term and pre-term newborn infants who planned to breast-feed their
      newborn infants were considered for this study. They were consecutively recruited
      in one of 3 groups of 14, according to delivery method: group 1, vaginal delivery
      at term (gestational age 40.2 +/- 0.3 weeks; birth weight, 3.48 +/- 0.09 kg);
      group 2, preterm vaginal delivery (gestational age, 35.6 +/- 0.3 weeks; birth
      weight, 2.49 +/- 0.08 kg); and group 3, at-term elective cesarean section
      (gestational age, 39.0 +/- 0.3 weeks; birth weight, 3.32 +/- 0.14 kg). Three
      consecutive breast milk samples were obtained on the fourth day after birth,
      before each mother's discharge, and thereafter on the 10th and 30th postpartum
      days, close to expression of the colostrum, transitional, and mature milk
      production phases, respectively, to test beta-EP concentrations (beta-Endorphin
      125I RIA; INCSTAR Corporation, Stillwater, MN). Data are presented as mean +/-
      standard deviation. Statistical comparison of beta-EP concentration among the
      three lactating mother groups was performed using the Kruskal-Wallis
      nonparametric test. In addition, to test the hypothesis of a trend toward smaller
      values with time of beta-EP, the authors computed within each mother group a P
      value per trend (Kruskal-Wallis test) of beta-EP concentration averages on the
      4th, 10th, and 30th days, respectively. Student's t test for independent samples
      was used for the analysis of the other data. The 0.05 significance level was used
      in the statistical analysis. All computations were made by computer. RESULTS:
      Colostrum beta-EP concentrations on the fourth postpartum day of group 1 and
      group 2 mothers who were delivered of a neonate vaginally, at term, or
      prematurely were significantly higher (P < 0.01) than colostrum levels of group 3
      mothers who underwent cesarean section. Group 2 mothers who were delivered of a
      neonate vaginally and prematurely presented the highest beta-EP concentrations (P
      < 0.05), lasting until the transitional milk phase (10th day). No significant
      differences were found across all 3 groups of lactating mothers in mature milk
      (30th day) beta-EP concentrations. In addition, the beta-EP trend toward smaller
      values with time within each of the three groups on days 4, 10, and 30 was
      statistically significant (P < 0.01 per trend). CONCLUSIONS: It is hypothesized
      that elevated beta-EP concentrations in colostrum and transitional milk of
      mothers who were vaginally delivered of infants may contribute to postnatal fetal
      adaptation, to overcoming birth stress of natural labor and delivery, and at the
      same time to the postnatal development of several related biologic functions of
      breast-fed infants.

PMID- 11568518
TI  - Age-dependent changes in the regulation of cyclooxygenases in the
      gastrointestinal tract after gram-negative endotoxemia.
AB  - BACKGROUND: Cyclooxygenases (COXs) modulate prostaglandin synthesis in the
      gastrointestinal tract. Prostaglandins have been shown to have a cytoprotective
      effect on bowel mucosa in adults, but no similar data are available in neonates.
      Thus, the purpose of the current study was to evaluate age-dependent changes in
      gastrointestinal tract COX regulation after Escherichia coli lipopolysaccharide
      exposure in rats. METHODS: Stomach, small bowel, and large bowel COX-1 and COX-2
      mRNA levels (reverse transcription polymerase chain reaction technique) and
      protein content (Western blot) were obtained from neonates (younger than 3 days
      old) and adult rats 18 hours after exposure to E. coli O111:B4 lipopolysaccharide
      toxin. Untreated animals served as controls. RESULTS: Stomach, small bowel, and
      large bowel tissue COX-1 mRNA levels in the newborn were significantly lower (P <
      0.01) than in the adult. No age-dependent differences were found for COX-2 mRNA
      levels. After lipopolysaccharide exposure, no significant changes in COX-1 levels
      were seen at either age, whereas COX-2 mRNA levels were increased only in the
      stomach for both ages. Western blot analysis of small bowel tissue for COX-1 and
      COX-2 showed no lipopolysaccharide-induced changes in protein content, but the
      COX-1 content was significantly lower in the newborn (P < 0.01). CONCLUSIONS: In
      the rat, COX expression in the gastrointestinal tract is regulated in an age
      dependent fashion. Lower COX-1 expression and a lack of observable increase in
      COX-2 mRNA levels in the newborn small bowel after endotoxemia may render the
      bowel more susceptible to bowel injury early in life.

PMID- 11568519
TI  - Probiotic treatment using Bifidobacterium lactis HN019 reduces weanling diarrhea
      associated with rotavirus and Escherichia coli infection in a piglet model.
AB  - BACKGROUND: Diarrhea associated with rotavirus and Escherichia coli is one of the
      major gastrointestinal problems faced by human infants. Using a piglet model, the
      authors investigated the protective effectiveness of probiotic feeding against
      naturally acquired diarrhea in weanlings. METHODS: Seventeen piglets were
      allocated into two groups balanced for live weight and litter of origin. The test
      group was administered Bifidobacterium lactis HN019 (109 colony-forming units
      (cfu)/piglet/d) orally until the end of the experiment; the control group did not
      receive probiotic treatment. After 1 week, animals were penned individually and
      weaned onto a diet for a weaner. The degree of subsequent diarrheal disease was
      monitored in both groups of animals, feed intake and live weight gain of the
      piglets were assessed, and blood and fecal samples were collected to measure
      concurrent systemic and gastrointestinal tract immunologic activity. RESULTS:
      Compared with the controls, piglets that received B. lactis HN019 had a lower
      severity of weanling diarrhea and maintained a greater feed conversion efficiency
      during weaning. The protective effect of probiotic feeding was associated with
      lower concentrations of fecal rotavirus and E. coli, higher blood leukocyte
      phagocytic and T-lymphocyte proliferative responses, and higher gastrointestinal
      tract pathogen-specific antibody titers. CONCLUSIONS: These results show that
      dietary treatment using B. lactis HN019 can reduce the severity of weanling
      diarrhea associated with rotavirus and E. coli, possibly via a mechanism of
      enhanced immune-mediated protection. This study suggests that probiotic treatment
      may be an effective dietary means of preventing or limiting diarrhea in human
      infants.

PMID- 11568520
TI  - The effect of cisapride on the corrected QT interval and QT dispersion in
      premature infants.
AB  - BACKGROUND: Cisapride is used frequently in premature neonates as a
      gastrointestinal prokinetic drug. Concerns exist, however, about its safety
      because of its effect on the QT interval. Premature infants could be at higher
      risk for side effects because of their immaturity. This prospective study
      investigated the pharmacokinetics of cisapride and its effects on corrected QT
      interval (QTc) and QT dispersion in premature infants. METHODS: Electrocardiogram
      examination was performed just before and after 72 hours of treatment with
      cisapride (0.2 mg/kg per dose, four times daily) in 10 premature infants. Trough
      and anticipated peak plasma level of cisapride and norcisapride were quantified
      after 72 hours of treatment. Results were compared with a cohort of 41 term
      infants aged 0 to 3 months receiving cisapride treatment. RESULTS: The QTc
      interval increased significantly from 423 ms to 461 ms after 72 hours of
      treatment (P = 0.0007). No effect was seen on QT dispersion (44.3 ms vs. 45.9
      ms). The change in QTc interval was inversely related to postnatal age (R2 =
      0.52; P = 0.02), whereas there was no correlation with gestational age or plasma
      levels of cisapride or norcisapride. Trough and anticipated peak plasma levels of
      cisapride and norcisapride were significantly higher in the premature infants
      compared with the term infants aged 0 to 3 months (P < 0.001). CONCLUSIONS:
      Premature infants less than 1 month of age could be at higher risk for cardiac
      side effects of cisapride when used in the same dosage as in older infants. The
      daily dose should be reduced (0.1 mg/kg per dose, maximum four times daily), and
      the QTc interval should be monitored closely. The benefits and safety of
      cisapride in premature infants less than 1 month of age should be reconsidered.

PMID- 11568521
TI  - Chronic subcutaneous octreotide decreases gastrointestinal blood loss in blue
      rubber-bleb nevus syndrome.
AB  - BACKGROUND: A patient affected by blue rubber-bleb nevus syndrome had chronic
      gastrointestinal bleeding requiring weekly blood transfusions. Despite multiple
      surgical and endoscopic procedures to treat the venous malformations, the patient
      continued to bleed primarily from lesions in the small bowel. Therefore, this
      patient was treated with octreotide, a somatostatin analog known to decrease
      splanchnic blood flow and that is used for acute and chronic gastrointestinal
      bleeding. METHODS: Octreotide therapy, 5.7 microg/kg subcutaneously twice daily,
      was initiated, and the patient was followed up clinically. Complete blood counts,
      blood glucose concentration, pancreatic enzyme concentration, liver function
      tests, and growth hormone concentration were monitored during treatments.
      RESULTS: During the 4 weeks after initiation of octreotide therapy, hemoglobin
      concentration was maintained without the need for transfusions. Octreotide
      decreased the patient's monthly need for blood transfusion from 52 +/- 7 mL. kg
      1. mo-1 of packed red blood cells to 23 +/- 7 mL. kg-1. mo-1. She had no
      detectable side effects or growth inhibition. Other medical interventions
      including -epsilonaminocaproic acid, nadolol, and total parenteral nutrition with
      bowel rest were not as effective as octreotide alone. CONCLUSION: Octreotide
      decreased the patient's need for blood transfusions. Possible mechanisms include
      altering blood flow to the gastrointestinal tract and direct effects on the
      venous malformations.

PMID- 11568522
TI  - Intestinal protein and LPH synthesis in parenterally fed piglets receiving
      partial enteral nutrition and enteral insulinlike growth factor 1.
AB  - BACKGROUND: Providing partial enteral nutrition (PEN) supplemented with
      insulinlike growth factor-1 (IGF-1) to parenterally fed piglets increases lactase
      phlorizin hydrolase (LPH) activity, but not LPH mRNA. The current aim was to
      investigate potential mechanisms by which IGF-1 up-regulates LPH activity.
      METHODS: Newborn piglets (n = 15) received 100% parenteral nutrition (TPN), 80%
      parenteral nutrition + 20% parenteral nutrition (PEN), or PEN + IGF-1 (1.0 mg. kg
      1. d-1) for 7 days. On day 7, [2H3]-leucine was intravenously administered to
      measure mucosal protein and brush border LPH (BB LPH) synthesis. RESULTS: Weight
      gain, nutrient intake, and jejunal weight and length were similar among the
      treatment groups. Partial enteral nutrition alone increased mucosal weight,
      villus width and cross-sectional area, LPH activity, mRNA expression, and high
      mannose LPH precursor (proLPHh) abundance compared with TPN (P<0.05). Insulinlike
      growth factor-1 further increased mucosal weight, LPH activity, and LPH activity
      per unit BB LPH approximately twofold over PEN alone (P < 0.05) but did not
      affect LPH mRNA or the abundance of proLPHh (one of the LPH isoforms) or mature
      LPH. Isotopic enrichment of [2H3]-leucine in plasma, mucosal protein, and LPH
      precursors, and the fractional and absolute synthesis rates of mucosal protein
      and LPH were similar among the treatment groups. Insulinlike growth factor-1
      treatment increased total mucosal protein synthesis (60%, P < 0.05) but not LPH
      synthesis compared with the other two groups. CONCLUSIONS: Because IGF-1 did not
      affect the fractional synthesis rate of either mucosal protein or LPH, the
      authors suggest that enteral IGF-1 increases mucosal protein mass and LPH
      activity by suppressing mucosal proteolytic degradation.

PMID- 11568523
TI  - Clear cell tumor of the colon in an 8.5-year-old girl.

PMID- 11568524
TI  - Coexistence of celiac disease and eosinophilic gastroenteropathy.

PMID- 11568525
TI  - Congenital mediastinal cystic abnormalities detected in utero: report of two
      cases.

PMID- 11568526
TI  - Ataxia with isolated vitamin E deficiency: case report and review of the
      literature.

PMID- 11568527
TI  - Coinheritance of Rotor syndrome, G-6-PD deficiency, and heterozygous beta
      thalassemia: a possible genetic interaction.

PMID- 11568528
TI  - Auto-brewery syndrome in a child with short gut syndrome: case report and review
      of the literature.

PMID- 11568529
TI  - Mucopolysaccharidosis type VII (Sly syndrome) presenting as neonatal cholestasis
      with hepatosplenomegaly.

PMID- 11568530
TI  - Early speech delay and hepatitis as presenting signs of homocystinuria.

PMID- 11568531
TI  - Rise of medical specialization and organizations affecting otolaryngology.
AB  - As we enter the third millennium, there are in the United States 24 medical
      specialties recognized by the American Board of Medical Specialties. The majority
      of the members of each of these specialties have their education, training, and
      knowledge "certified" by an examining board unique to their specialty. One
      hundred years ago virtually none of the foregoing existed. At the turn of the
      20th century, nearly all physicians practiced all of medicine. How and why did
      this evolution occur and what controls evolved to contain this? The goal of this
      presentation is to review the rise of medical specialties and the board
      examination system and describe some of the many organizations, often known by
      acronyms, which deal with this now complex architecture.

PMID- 11568532
TI  - Osseous tissue engineering with gene therapy for facial bone reconstruction.
AB  - OBJECTIVE: Facial osseous defects remain a major functional and esthetic
      challenge for the head and neck surgeon. Tissue engineering may provide
      advantageous alternatives to conventional therapies. The objective of the study
      was to evaluate the efficacy of gene therapy in the repair of osseous facial
      defects. STUDY DESIGN: Blinded, controlled, prospective animal experiment.
      METHODS: Thirty adult athymic nude rats were divided into five groups of six
      animals. Three groups were used as control subjects. Two groups were treated with
      3.75 x 10(8) viral particles containing recombinant type 5 adenoviral vectors.
      One group received viruses that coded for beta-galactosidase production, another
      received viruses that coded for bone morphogenetic protein (BMP-2) production.
      After 120 days rats were examined at necropsy with precise planimetry,
      histological analysis of new bone growth, and radio-densitometric analysis of
      bone thickness. RESULTS: Radio-densitometric measurements showed that BMP-2
      treated nude athymic rats had significantly enhanced osseous repair compared with
      control subjects when evaluated by both radio-densitometry and histological
      examination. CONCLUSION: Gene therapy-treated, immunosuppressed rodents had an
      enhanced osteoinductive repair of a dorsal osseous nasal defect.

PMID- 11568533
TI  - Distraction osteogenesis of the mandible for airway obstruction in children.
AB  - OBJECTIVES: Objectives of the study were to determine the effectiveness of
      distraction osteogenesis of the mandible to relieve airway obstruction in
      children with tongue-base airway obstruction and to describe the new surgical
      techniques developed for use in infants and young children. STUDY DESIGN:
      Prospective, nonrandomized study. METHODS: Analysis of 11 children with severe
      airway obstruction secondary to tongue-base obstruction was performed. Patients
      were between 2 weeks and 5.5 years of age. All patients underwent distraction
      osteogenesis of the mandible. RESULTS: Twelve distraction procedures in the 11
      children in the study were accomplished; decannulation or extubation was
      successful in all children. CONCLUSION: Distraction osteogenesis of the mandible
      can be used to treat tongue-base airway obstruction in appropriately selected
      children.

PMID- 11568534
TI  - L-n-acetyl-cysteine protection against cisplatin-induced auditory neuronal and
      hair cell toxicity.
AB  - OBJECTIVES: The aim of this study is to determine the efficacy of L-N-acetyl
      cysteine (L-NAC) as a protectant for inner ear auditory sensory cells against the
      toxic effects of cisplatin. STUDY DESIGN: Prospective laboratory study of the
      otoprotective effect of L-NAC on auditory neurons and hair cells in vitro.
      METHODS: The study has two arms. The first arm evaluated the neuroprotective
      effect of L-NAC on early postpartum auditory ganglion cell cultures. Two culture
      media were used. The two media differed in that one of them was enhanced by the
      addition of neurotrophins (neurotrophin type 3 and brain-derived neurotrophic
      factor) and a growth factor (transforming growth factor-beta1). Then the survival
      of cisplatin-treated auditory neurons was studied before and after pretreatment
      with protective levels of L-NAC. The second arm of the study evaluated the effect
      of L-NAC on cisplatin damage initiated to auditory hair cells. Early-postpartum
      organ of Corti explants were grown in culture. Their rate of survival was studied
      after exposure to toxic levels of cisplatin. Then, survival of cisplatin-damaged
      hair cells was studied after they were pretreated with L-NAC. RESULTS:
      Pretreatment of cultures with L-NAC protected both auditory neurons and hair
      cells from the effects of exposure to toxic levels of cisplatin. This observed
      otoprotective effect was dose dependent. CONCLUSIONS: Our in vitro studies have
      demonstrated that L-NAC protected both auditory neurons and hair cells from the
      toxic effects of cisplatin. Because it protects both of these inner ear
      structures, L-NAC may be potentially useful in protecting hearing, in general,
      from cisplatin-induced damage. In addition, L-NAC has low systemic and mucosal
      toxicity. It also has a low molecular weight that may allow it to readily cross
      the round window membrane. All these characteristics make it potentially suitable
      for transtympanic application for the prevention of the ototoxicity of cisplatin
      in vivo.

PMID- 11568535
TI  - Potassium recycling pathways in the human cochlea.
AB  - OBJECTIVES/HYPOTHESIS: Potential pathways for recycling potassium (K+) used in
      the maintenance of inner ear electrochemical gradients have been elucidated in
      animal models. However, little is known about K+ transport in the human cochlea.
      This study was designed to characterize putative K+ recycling pathways in the
      human ear and to determine whether observations from animal models can be
      extrapolated to humans. STUDY DESIGN: A prospective laboratory study using an
      immunohistochemical approach to analyze the distribution of key ion transport
      mediators in the human cochlea. METHODS: Human temporal bones were fixed in situ
      within 1 to 6 hours of death and subsequently harvested at autopsy.
      Decalcification was accomplished with the aid of microwaving. Immunohistochemical
      staining was then performed to define the presence and cell type-specific
      distribution of Na,K-ATPase, sodium-potassium-chloride cotransporter (NKCC), and
      carbonic anhydrase (CA) in the inner ear. RESULTS: Staining patterns visualized
      in the human cochlea closely paralleled those seen in other species. Anti-Na,K
      ATPase stained strongly the basolateral plasma membrane of strial marginal cells
      and nerve endings underlying hair cells. This antibody also localized Na,K-ATPase
      to type II, type IV, and type V fibrocytes in the spiral ligament and in limbal
      fibrocytes. NKCC was present in the basolateral membrane of strial marginal cells
      as well as in type II, type V, and limbal fibrocytes. Immunoreactive carbonic
      anhydrase was present in type I and type III fibrocytes and in epithelial cells
      lining Reissner's membrane and the spiral prominence. CONCLUSIONS: The
      distribution of several major ion transport proteins in the human cochlea is
      similar but not identical to that described in various rodent models. These
      results support the presence of a complex system for recycling and regulating K+
      homeostasis in the human cochlea, similar to that described in other mammalian
      species.

PMID- 11568536
TI  - Improving the otolaryngology consultation service in a teaching hospital.
AB  - OBJECTIVE: To examine the type and quality of consultations requested from the
      otolaryngology service at a tertiary care hospital. STUDY DESIGN: Retrospective.
      METHOD: Review of written documentation of consultations over a 6-month period.
      RESULTS: One hundred eleven requests were received, and 107 written reports were
      made. Twenty services made requests. Thirty-two percent of requests had a legible
      requester or contact listed. Sixty-seven percent of requests stated why the
      patient was in hospital, and 85% stated the otolaryngological complaint. Thirty
      two percent of requests made accurate reference to the otolaryngological history,
      and 6% recorded an ENT examination that was accurate. Seven percent of patients
      were intubated, and 16% had a tracheostomy prior to evaluation. Forty-eight
      percent of patients required flexible nasopharyngolaryngoscopy. Sixteen percent
      of patients required rhinoscopy, and 16% required tracheotomy. Twelve percent of
      patients needed audiograms, and small numbers of patients required biopsy,
      debridement of ears, ventilation tube insertion, nasal packing, or radiological
      studies. Reports were made by senior residents, and evidence that the case was
      discussed with or seen by an attending surgeon was present in 43% of reports. A
      diagnosis was stated in 85% of reports, and in 3% the diagnosis appeared to be
      inaccurate as compared with the history and physical examination recorded. A
      follow-up plan was stated in 70% of reports. CONCLUSIONS: There is a need to
      educate physicians about collegial communication regarding patients. This
      information can direct curriculum needed to prepare otolaryngology residents to
      provide a consultative service in a teaching hospital. This method of determining
      "true learning needs" can be used in other situations to improve resident
      training.

PMID- 11568537
TI  - Cost/benefit analysis of open tracheotomy, in the or and at the bedside, with
      percutaneous tracheotomy.
AB  - OBJECTIVES/HYPOTHESIS: (1) To determine whether percutaneous dilational
      tracheotomy (PDT), open tracheotomy in the operating room (OT/OR), and open
      tracheotomy at the bedside (OT/BS) are equally safe; and (2) to determine which
      procedure was most cost effective. STUDY DESIGN: Retrospective review of patient
      medical records and billing data. METHODS: Any adult patient (>20 y of age) on
      the medical or surgical services at Penn State Milton S. Hershey Medical Center
      who required a tracheotomy, elective or emergent, from September 1996 to July
      1997 was included. The decision to perform OT in the OR, PDT, or OT at BS was
      made by the attending surgeon independent of this study. Each patient's course
      after tracheotomy was reviewed. All complications, perioperatively or
      postoperatively, for up to 10 days were documented. The complications were
      divided into two groups: major and minor. Determination of patient cost used
      surgical billing and OR materials staff records. The necessary equipment and
      staff for each procedure was determined, and an itemized cost list was
      retrospectively developed for a typical PDT, OT in OR, or OT at BS. The P values
      were calculated with the Cochran-Mantel-Haenszel (CMH) chi(2) test of
      association. RESULTS: All procedures were equally safe, with PDT being the most
      cost effective. CONCLUSION: This report confirms the results of several studies
      demonstrating that PDT, OT in the OR, and OT at the BS are equally safe; PDT
      appears to be most cost effective. Our analysis, however, does reveal several
      options for decreasing the cost of bedside tracheotomy to allow this procedure to
      be even more cost effective than PDT.

PMID- 11568538
TI  - An investigation of airway wound healing using a novel in vivo model.
AB  - OBJECTIVE: To study the amount of wound contraction and reepithelialization
      occurring in the healing process of full-thickness mucosal defects treated with
      and without mitomycin. STUDY DESIGN: A new wound healing model was developed in
      which the tracheal mucosa was exteriorized without interference with the blood
      supply or with the cartilage support of the trachea. This was done by: 1)
      orthotopic tracheal revascularization in vascularized fascia; 2) isolation of
      revascularized segment after 14 days; 3) posterior longitudinal incision of
      revascularized segment; 4) exteriorization of tracheal mucosa with formation of
      anterior full-thickness mucosal defect; and 5) closure of posterior tracheal
      incision and reimplantation in the airway. This model was used to study airway
      wound healing in three groups of animals: 1) controls (revascularization,
      exteriorization, reimplantation) (N = 6); 2) full-thickness mucosal defect: patch
      defect (N = 5), circumferential defect (N = 3); and 3) full-thickness mucosal
      defect after topical mitomycin application: patch defect (N = 7), circumferential
      defect (N = 3). The animals were followed for periods varying from 2 to 4 weeks
      or until signs of dyspnea. The surface areas of the wounds before and after
      follow-up were measured. Wound healing was studied histologically on axial and
      longitudinal sections. RESULTS: Group 1: All the animals survived for 1 month. No
      significant difference existed between surface area of isolated trachea and of
      reimplanted trachea after follow-up. Group 2: Five animals (patch defects)
      survived for 1 month. Full-thickness mucosal defects healed by
      reepithelialization and by a surface area reduction of 58.9% (mean - standard
      deviation = 10.5). The animals with the circumferential defects showed dyspnea
      after an average follow-up of 14 days as a result of excessive granulation tissue
      formation. Group 3: Mitomycin reproducibly inhibited wound closure, yielding
      wounds that on average closed 56% less than controls by day 14 (P <.001).
      Histologic comparisons showed that mitomycin blocks angiogenesis during wound
      healing. CONCLUSIONS: A wound healing model based on tracheal revascularization,
      isolation, and reimplantation was developed in rabbits. This model allowed us to
      study the healing of full-thickness mucosal defects inside the airway.

PMID- 11568539
TI  - Functional magnetic resonance imaging of the pediatric swallow: imaging the
      cortex and the brainstem.
AB  - OBJECTIVE: To design and implement a functional magnetic resonance imaging (fMRI)
      protocol to investigate the cortical and brainstem patterns of activity in
      children with regard to the act of swallowing. STUDY DESIGN: Pilot study to
      assess the clinical feasibility of the project. METHODS: Using a 3T Bruker
      Biospec 30/60 MRI scanner, images were obtained using the Behavior Interleaved
      Gradient/Blood Oxygen Level Dependent (BIG-BOLD) image acquisition method.
      Initially, regions of interest (ROI) were developed to identify the mean time
      from the onset of a swallow to maximum cortical blood flow in the motor cortex.
      Using this data to design the BIG-BOLD acquisition method followed by
      postprocessing of the data, images from two volunteer adults and four volunteer
      children were obtained. RESULTS: The average time from the onset of a swallow to
      maximum cortical blood flow was 6 to 8 seconds. Regions of cortical activity
      include pre- and post-central gyrus (Brodmann's areas 3 and 4), superior motor
      cortex (B.A. 24), insula, inferior frontal cortex (B.A. 44 and 45), Heschl gyrus
      (B.A. 41 and 42), putamen, globus pallidus, and the superior temporal gyrus (B.A.
      38). Of particular note is the first mapping of the functional activity of
      swallowing at the level of the brainstem; activity was seen in the region of the
      nucleus ambiguous. CONCLUSIONS: fMRI provides a novel means of studying the
      central processes of both normal swallowing and its various pathologic forms in
      children. Further understanding of how a child coordinates a swallow and how this
      coordination can be altered at the level of the brainstem and cortex may aid in
      the development of novel rehabilitative strategies.

PMID- 11568540
TI  - Free tissue reconstruction of the hypopharynx after organ preservation therapy:
      analysis of wound complications.
AB  - PURPOSE: Previous series have demonstrated a 77% rate of major wound
      complications in salvage surgery of the larynx following organ preservation
      protocols. The purpose of this study is to determine the incidence of wound
      complications in these patients when microvascular free tissue transfers are used
      for reconstruction of the hypopharynx. DESIGN: Retrospective case series.
      SETTING: Academic tertiary care center. PATIENTS AND METHOD: We reviewed the
      medical records of 42 patients with stage III and IV laryngeal squamous cell
      carcinoma treated with an organ-sparing protocol consisting of induction
      chemotherapy followed by definitive radiation therapy. Ten of these patients who
      required surgical salvage were reconstructed using radial forearm free tissue or
      lateral arm transfer and constitute the study group. MAIN OUTCOME MEASURES: Wound
      complications. RESULTS: Wound complications occurred in 2 patients (20%)
      undergoing free flap reconstruction of the hypopharynx after organ preservation
      protocols, which was significantly lower (P =.003) than previous reports using
      other forms of closure and/or reconstruction. One patient in this study group had
      a small pharyngocutaneous fistula that resolved with conservative therapy after 1
      week. The other patient had a larger pharyngocutaneous fistula that resolved over
      3 weeks. The mean interval from completion of the chemoradiation regimen to
      surgery was 21.3 months (range, 2-60 mo). The average free tissue flap size was
      94.3 cm(2) (range, 45-165 cm(2)). Average harvest and ischemia times were 59
      minutes (range, 41-87 min) and 187.7 minutes (range, 120-240 min), respectively.
      All flaps survived, and one patient had a minor donor site wound dehiscence. The
      average hospital stay was 7.8 days. There were no mortalities in this series.
      CONCLUSIONS: Our results suggest that free tissue transfer reconstruction of the
      hypopharynx is the preferred method of reconstruction following combined
      chemotherapy and radiation therapy protocols. Surgical complications are
      significantly reduced and hospital stays are minimized.

PMID- 11568541
TI  - Laryngeal angiosarcoma: a clinicopathologic study of five cases with a review of
      the literature.
AB  - OBJECTIVE: Primary laryngeal angiosarcoma (LA) is rare without a reported series
      evaluating these tumors. STUDY DESIGN/METHODS: Five patients with LA were
      retrospectively retrieved from the Otorhinolaryngic Registry of the Armed Forces
      Institute of Pathology. RESULTS: Three men and 2 women, aged 29 to 71 years,
      presented with hoarseness (n = 4) and hemoptysis (n = 1). Two patients had
      previous neck radiation. The tumors involved the supraglottis (n = 4) with a mean
      size of 3.1 cm. Histologically, all tumors had anastomosing vascular channels
      lined by remarkably atypical endothelial cells protruding into the lumen,
      frequent atypical mitotic figures, and hemorrhage. All cases tested (n = 4)
      demonstrated immunoreactivity with antibodies to Factor VIII-RA and CD34. All
      patients had surgery followed by postoperative radiation (n = 3 patients). Three
      patients died with disease (mean, 17 mo), whereas one patient is alive with no
      evidence of disease at 18 years. CONCLUSIONS: LA is a rare tumor, frequently
      associated with previous radiation, usually involving the supraglottis with
      characteristic histomorphologic and immunophenotypic features. LA has a poor
      prognosis, making appropriate separation from other conditions important.

PMID- 11568542
TI  - Pulsed-dye laser and retinoic acid delay progression of oral squamous cell
      carcinoma: a murine model.
AB  - OBJECTIVES/HYPOTHESIS: This study examined the role of the pulsed-dye laser (PDL)
      at 585 nm coupled with retinoic acid at therapeutic (5.0 mg/kg) and
      nontherapeutic (0.5 mg/kg) doses to delay the progression of cancer with a two
      hit approach. The existing vasculature is selectively targeted by the laser,
      whereas retinoic acid inhibits future angiogenesis. STUDY DESIGN: Randomized,
      prospective study in a murine model. METHODS: Twenty-five athymic nude mice were
      inoculated with oral squamous cell cancers on six flank sites and randomly
      divided into five groups: 1) control subjects, 2) treatment with 0.5 mg/kg
      retinoic acid (RA 0.5), 3) treatment with 5.0 mg/kg retinoic acid (RA 5.0), 4)
      treatment with RA 0.5 + PDL, and 5) treatment with RA 5.0 + PDL. The PDL groups
      received irradiation after inoculation. The retinoic acid was administered daily.
      The tumors were counted and measured for 14 days. RESULTS: The control group
      developed visible tumors in 50% of the inoculation sites at 3 days compared with
      3 days (RA 0.5) and 4 days (RA 5.0) for the retinoic acid groups and 9 days (RA
      0.5 + PDL) and 10 days (RA 5.0 + PDL) for the laser treatment groups. There was
      no tumor growth until day 7 in the RA 5.0 + PDL group. The tumor volume was
      statistically different between the treatment groups. CONCLUSION: This study
      demonstrated the superiority of a single treatment with the PDL coupled with
      retinoic acid to delay the progression of cancer when compared with treatment
      with retinoic acid alone, thus introducing a novel strategy in cancer control.

PMID- 11568543
TI  - Melanoma of the head and neck: current concepts in diagnosis and management.

PMID- 11568544
TI  - Improved postoperative pain control in pediatric adenotonsillectomy with
      dextromethorphan.
AB  - DESIGN: A prospective, randomized, double-blinded, placebo-controlled protocol.
      SETTING: An academic, tertiary care referral center. PATIENTS: Forty randomly
      selected children, ages 3 to 13 years, scheduled for adenotonsillectomy without
      other simultaneous procedures. INTERVENTION: A single, oral dose of
      dextromethorphan pediatric cough syrup (1 mg/kg) or placebo given 30 minutes
      before surgery. MAIN OUTCOME MEASURE: Total dose requirement of intravenous
      morphine within a 6-hour postoperative observation period. RESULTS: During
      routine postoperative observation, significantly fewer patients in the
      dextromethorphan group required no intravenous morphine compared with the placebo
      group (P =.03). Of those children requiring morphine, the mean dose requirement
      was significantly lower in the dextromethorphan group (P =.02). There was no
      known drug-related morbidity. CONCLUSION: Dextromethorphan syrup is a safe, non
      narcotic medication that significantly reduced the requirement of intravenous
      morphine after pediatric adenotonsillectomy. Its routine use in this manner is
      recommended.

PMID- 11568545
TI  - Nasal ciliary function and ultrastructure in Down syndrome.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the in vivo nasal ciliary beat and the
      ciliary ultrastructure in Down syndrome because, although in this condition an
      increased susceptibility to respiratory tract infections has been reported by
      several authors, the nature of this phenomenon is not fully understood. STUDY
      DESIGN: Experimental study of 18 subjects with Down syndrome and 18 healthy
      control subjects. METHODS: Ciliary beat frequency (CBF) was measured on samples
      of ciliated epithelium obtained from the inferior nasal turbinate; a further
      brushing for ultrastructural analysis was performed only in subjects showing a
      CBF reduction or a ciliary movement alteration. RESULTS: The mean CBF in the
      group with Down syndrome was 7 +/- 2.82 Hz, and in the control subjects it was
      10.94 +/- 0.65 Hz. In the same 66.6% of subjects with Down syndrome, we observed
      a fibrillatory movement of cilia and no metachronicity was present. Moreover, in
      14 subjects with Down syndrome as hyperproduction of mucus was present.
      Ultrastructural evaluation at transmission election microscopy instead revealed a
      normal architecture of cilia. CONCLUSION: We attribute the nature of the
      mucociliary defect in Down syndrome to recurrent respiratory tract infections
      causing changes in mucus properties as in rheological parameters and not to a
      primitive defect of cilia.

PMID- 11568546
TI  - Comparison of wound healing using the CO2 laser at 10.6 microm and 9.55 microm.
AB  - OBJECTIVES/HYPOTHESIS: The wound healing characteristics of incisions made with
      the short pulsed CO2 laser tuned to 9.55 microm versus the traditional 10.6
      microm were investigated. Previous studies have shown that at 9.55 microm,
      collagen is targeted more selectively than at 10.6 microm, which results in
      decreased acute thermal injury patterns. This study investigates the difference
      in wound healing over time between lasers and compares laser incisions with cold
      knife techniques. STUDY DESIGN: Randomized controlled trial using a porcine
      model. METHODS: Tissue from 10.6-microm and 9.55-microm incisions of 10 piglets
      was evaluated with histological analysis and tensiometry at 3, 7, 14, and 21 days
      postoperatively. A Bonferroni-Dunn corrected analysis of variance analysis at a
      95% significance level was used to compare the effect of wavelength. RESULTS: The
      results demonstrate that although knife incisions are consistently stronger than
      laser incisions, the 9.55-microm CO2 laser incisions are no stronger than
      incisions made with the conventional 10.6-microm laser. Furthermore, histological
      analysis shows no difference in lateral thermal damage between lasers at 3, 7,
      14, and 21 days postoperatively. The progression of collagen formation and
      inflammation does not differ over time. CONCLUSION: This study of wound healing
      using a porcine model demonstrates that the 9.55-microm CO2 laser does not
      demonstrate an improvement in wound healing over the traditional 10.6-microm CO2
      laser. These results may be secondary to the common explosive vaporization
      mechanism produced by both lasers in the infrared spectrum.

PMID- 11568547
TI  - Rhino-frontal sinuseptotomy (RFS): a combined intra-extra nasal approach for the
      surgical treatment of severely diseased frontal sinuses.
AB  - OBJECTIVES: Frontal sinus surgery is a challenge to those involved in the
      treatment of recurrent frontal sinusitis. The purpose of this report is to
      describe the technique and to present the results of a combined endoscopic and
      external approach to the frontal sinus (rhino-frontal sinuseptotomy [RFS]).
      MATERIAL: RFS was performed in 45 patients by the author; 41 of these patients
      had a follow-up over 12 months and were included in this series. Indications for
      RFS were severe chronic frontal sinusitis (n = 23), mucoceles (n = 12), in two
      cases each with osteoma, inverting papilloma, and malignant tumors of the frontal
      sinus, respectively. The surgical technique is started with an external approach
      according to Jansen-Ritter and includes the resection of the interfrontal septum,
      partial resection of the nasal septum, bilateral subtotal resection of the middle
      turbinates, bilateral endoscopic ethmoidectomy, and resection of the frontal
      sinus floor. The nasofrontal communication is epithelialized with free mucosal
      grafts and fixed with fibrin clue. RESULTS: After a mean follow-up of 62 months,
      40 patients (98%) had a widely patent epithelialized nasofrontal communication.
      Ninety-one percent of the patients with chronic frontal sinusitis or mucoceles
      noted complete relief of their frontal discomfort within 1 week after RFS. No
      patient required revision surgery of the nasofrontal outflow tract after RFS.
      Only one severe complication was recognized (cerebrospinal fluid leakage).
      CONCLUSION: The results reported here with the RFS technique are superior to
      those reported on external procedures and endoscopic drill-out procedures. The
      key to successful management is the creation of a large nasofrontal
      communication, and direct epithelialization with free mucosal grafts obtained
      from the septum and turbinates.

PMID- 11568548
TI  - Combined external and endoscopic frontal sinusotomy with stent placement: a
      retrospective review.
AB  - OBJECTIVES: To examine the long-term results of combined external and endoscopic
      frontal sinusotomy using frontal sinus stents and to compare our results with
      those reported for the endoscopic Lothrop procedure. STUDY DESIGN: We performed a
      retrospective review of 40 patients with chronic frontal sinusitis refractory to
      medical management who underwent a total of 62 combined external and endoscopic
      frontal sinusotomies with stent placement. All procedures were performed by the
      senior author at Vanderbilt University Medical Center. MAIN OUTCOME MEASURES:
      Postoperative nasofrontal duct patency and subjective patient improvement based
      on the last clinical examination. RESULTS: The overall patency rate of the
      nasofrontal duct was 79% (95% confidence interval [CI] of +/-10%.) The overall
      subjective patient improvement rate was 78% (95% CI of +/-14%.). The average
      length of stent placement was 5 weeks. The mean patient follow-up time was 12
      months. There were no surgical complications. The nasofrontal duct patency rate
      and patient improvement rate from our study did not differ statistically from
      results reported by other authors using the endoscopic Lothrop procedure.
      CONCLUSION: We have found endoscopic frontal sinusotomy, in conjunction with
      external frontal sinusotomy and placement of frontal sinus stents, to be as
      effective in obtaining frontal sinus patency rates and overall patient
      improvement rates as the endoscopic Lothrop procedure.

PMID- 11568549
TI  - Intratemporal facial nerve neuroma: anatomical location and radiological
      features.
AB  - OBJECTIVES: To present the imaging findings and anatomical locations of a series
      of 88 facial nerve neuromas from two centers over a 30-year period. We describe
      the salient radiological features of neuromas in each anatomical location and
      outline the ways in which modern imaging techniques have altered our perception
      of this entity. STUDY DESIGN: A retrospective review of tumors presenting to two
      tertiary care referral institutions since 1970. METHODS: The charts and available
      imaging of patients with the diagnosis of facial neuroma were reviewed. These
      patients presented to the House Ear Clinic between 1970 and 1994 and to the
      University of Utah Medical Center (Salt Lake City, UT) between 1986 and August
      2000. We examined anatomical location to determine patterns of tumor presentation
      and compared the findings before and after the era of magnetic resonance imaging
      (MRI). RESULTS: All segments of the facial nerve were represented. Overall,
      multiple-segment tumors were almost twice as common (63.6%) as single-segment
      tumors (36.4%). Before the advent of MRI, all segments of the nerve from the
      cerebellopontine angle to the tympanic portion were almost equally represented
      (29.5%-36.3%). After MRI, the geniculate ganglion (68.2%) and labyrinthine
      portion (52.3%) were by far the most commonly affected areas. Before MRI, there
      were, on average, 1.89 segments involved per tumor. After MRI, this average
      number increased to 2.57 segments per tumor. Radiologically, the high-resolution
      computed tomography and MRI features cannot be generalized. Rather, the imaging
      features depend on which segments are involved. This is because of the variation
      in the surrounding anatomical landscape of the facial nerve in its course through
      the temporal bone. CONCLUSION: The more sensitive imaging provided by newer
      radiological techniques has altered our perception of facial neuroma. It has
      provided us with an increased ability to diagnose and fully evaluate this
      neoplasm preoperatively, allowing improved patient counseling and surgical
      planning.

PMID- 11568550
TI  - Benign paroxysmal positional vertigo after stapedectomy.
AB  - OBJECTIVE: To determine the incidence of benign paroxysmal positional vertigo
      (BPPV) following stapedectomy in a patient group and the efficacy of the Epley
      maneuver in this group. STUDY DESIGN: Prospective study in a university-based
      tertiary referral system. METHODS: The patient group comprised 63 patients who
      had undergone stapedectomy; a control group consisted of normal healthy
      individuals with no otolaryngological complaints. All individuals underwent the
      Dix-Hallpike maneuver for the diagnosis of BPPV. Patients who exhibited vertigo,
      torsional nystagmus (which reverses its direction on return to sitting position)
      preceded by a latent period, and the fatigability of these findings were
      considered to have BPPV. If the test result was positive, they underwent the
      Epley therapeutic maneuver. RESULTS: Four of the patients who had undergone a
      stapedectomy showed characteristic findings of BPPV. No individual in the control
      group had BPPV. All patients responded well to the Epley maneuver. CONCLUSIONS:
      Stapedectomy may be regarded as an etiological factor in BPPV. Because the
      fenestra is located in the posterior part of the stapes footplate, the
      pathophysiology appears to be related to utricular rather than saccular trauma.
      Correct measurement of the distance between the incus and stapes footplate is
      essential in stapedectomy. An Internet survey of the relevant literature in
      English shows a scarcity of publications on the incidence of BPPV following
      stapedectomy. In the present study, 63 patients who had undergone a stapedectomy
      were investigated for the presence of BPPV; all had Dix-Hallpike maneuvers
      performed for the diagnosis. Sixty-three individuals with no otolaryngological
      complaints made up the control group. Four of the patients who had undergone
      stapedectomy showed characteristic findings of BPPV, and no individual in the
      control group had BPPV; the difference between the two groups was statistically
      significant. All four of the patients diagnosed with BPPV responded well to the
      Epley maneuver. The pathophysiology appears to be related to utricular trauma.
      Correct measurement of the distance between the incus and stapes footplate is
      essential in stapedectomy.

PMID- 11568551
TI  - Bone-anchored hearing aid quality of life assessed by Glasgow Benefit Inventory.
AB  - OBJECTIVE/HYPOTHESIS: The bone-anchored hearing aid (BAHA) is a well established
      mode of treatment and many studies show the audiological benefit, but none has
      assessed the benefit to the quality of life of patients. This study uses the
      validated Glasgow Benefit Inventory to quantify the changes in quality of life.
      STUDY DESIGN: Retrospective questionnaire study. METHODS: Sixty consecutive
      patients receiving treatment with BAHA were enrolled in the study. The
      male/female ratio was 1.26 to 1; mean patient age was 45 years. The most common
      indication was hearing loss secondary to mastoid disease and surgery followed by
      congenital atresia and chronic discharge from the ear. RESULTS: The response rate
      was 85%, which is high and adds weight to the results. The general benefit score
      was +34 (range, +27-+48), which is comparable to middle ear surgery but just
      below benefit from cochlear implantation. The social benefit was +21 (range, +12
      +37) with only +10 (range, +2-+26) for the physical score. This pattern mirrors
      that reported for other ear interventions. Maximum benefit was noted in patients
      with congenital atresias followed by discharging mastoid cavities. CONCLUSION:
      This study is the first to demonstrate significant quality of life benefit from
      BAHA surgical intervention as measured by the Glasgow Benefit Inventory.

PMID- 11568552
TI  - Degranulation of mast cells provokes a massive inflammatory reaction in the
      tympanic membrane.
AB  - OBJECTIVE: The pars flaccida is extremely rich in mast cells. On stimulation the
      mast cells release preformed and de novo synthesized inflammatory substances. The
      purpose of this study was to examine how these mast cell substances provoke
      inflammatory changes in the tympanic membrane. STUDY DESIGN: In vivo, murine
      model. METHODS: In a rat model, the mast cell secretagogue compound 48/80 was
      applied locally to the tympanic membrane on 4 consecutive days and the ensuing
      inflammatory changes were evaluated by otological, light, and electron microscopy
      3, 6, 9, 12, 18, 24, 36, and 48 hours and 4, 6, and 8 days later. RESULTS:
      Degranulation of the mast cells occurred within 3 hours of applying compound
      48/80. Release of the mast cell substances coincided with an inflammatory event
      characterized by a two-stage reaction: an edema stage, peaking 6 hours after
      application, followed by a massive invasion of inflammatory cells, peaking at 24
      and 48 hours. Pars flaccida and pars tensa were both involved, pars flaccida
      showing the earliest changes. Pars tensa exhibited the same biphasic reaction as
      pars flaccida, but approximately 6 hours later. CONCLUSIONS: The mast cells of
      the pars flaccida have the capacity to elicit an intense inflammation of the
      tympanic membrane. The biphasic reaction pattern resembles that observed in
      experimental otitis media, suggesting involvement of the mast cells in this
      inflammatory condition of the middle ear.

PMID- 11568553
TI  - Use of dexamethasone on the prophylaxis of nausea and vomiting after
      tympanomastoid surgery.
AB  - OBJECTIVE: The aim of this study was to evaluate the prophylactic effect of
      dexamethasone on postoperative nausea and vomiting (PONV) in patients undergoing
      tympanomastoid surgery. STUDY DESIGN: Eighty patients (n = 40 in each of two
      groups) undergoing tympanomastoid surgery under general anesthesia were enrolled
      in this randomized, double-blind, placebo-controlled study. METHODS: After
      tracheal intubation, group 1 received 10 mg dexamethasone intravenously, whereas
      group 2 received saline intravenously. Several parameters concerning with the
      occurrence of PONV were evaluated. RESULTS: We found that dexamethasone reduced
      the total incidence of nausea and vomiting by 45%, with a 95% confidence interval
      of 26% to 64% (P <.001). Furthermore, dexamethasone reduced the incidence of
      vomiting episodes >4 times and the incidence of patients requiring rescue
      antiemetics (P <.05). CONCLUSION: Dexamethasone at a dosage of 10 mg administered
      intravenously is effective in preventing PONV in patients undergoing
      tympanomastoid surgery.

PMID- 11568554
TI  - Decreased cochlear DNA receptor staining in MRL.MpJ-Fas(lpr) autoimmune mice with
      hearing loss.
AB  - OBJECTIVES: Previous studies of decreased cochlear DNA binding in autoimmune mice
      suggested that antibodies against a cochlear cell surface DNA receptor cause
      autoimmune hearing loss. However, the presence of a cochlear DNA receptor has not
      been determined. Therefore, immunohistochemistry with an anti-DNA receptor
      antibody was performed on MRL.MpJ-Fas(lpr) (MRL/lpr) autoimmune mice to determine
      1) which inner ear structures contain DNA receptors and 2) whether the receptor
      staining pattern changes as autoimmune disease progresses and hearing thresholds
      increase. STUDY DESIGN: A prospective study of the progression of hearing loss in
      autoimmune mice and correlated alterations in immunostaining for the inner ear
      DNA receptor. METHODS: One group of MRL/lpr mice (n = 10) was allowed to develop
      autoimmune disease, and auditory brainstem response (ABR) audiometry was
      performed at 4, 6, and 9 months of age to measure the progression of hearing
      loss. A second group (n = 5) was tested for ABR thresholds at 2 months of age and
      immediately killed to assess receptor staining before the onset of autoimmune
      disease and hearing loss. The inner ears from all mice were immunohistochemically
      stained with an anti-DNA receptor antibody, and a qualitative analysis of the
      staining of cochlear structures was performed. RESULTS: Auditory brainstem
      response audiometry revealed a significant 20- to 30-dB elevation of thresholds
      as systemic disease progressed. Anti-DNA receptor staining was heaviest in the
      spiral ligament and less intense in the spiral ganglion and cochlear nerve. Both
      groups showed a similar pattern of staining in these structures. The stria
      vascularis and hair cells also stained in both groups. However, the stria cells
      of normal-hearing mice showed diffuse intracellular immunoreactivity, whereas
      older mice displayed less staining that was confined to the cell membranes.
      CONCLUSIONS: The inner ears of MRL/lpr mice contain DNA receptors. Autoimmune
      hearing loss was correlated with weaker overall intracellular staining in the
      stria vascularis and hair cells but increased staining of the cell membranes.
      This suggested DNA receptors have impaired endocytosis and more receptors remain
      on the cell membrane, possibly as a result of binding by circulating
      autoantibodies.

PMID- 11568555
TI  - Surgical treatment of tracheostomal stenosis.
AB  - HYPOTHESIS: Stenosis of the tracheostome is a frequent complication following
      total laryngectomy; the problems created by tracheostomal stenosis are the result
      of reduced airflow and consequent turbulence. Many authors have studied
      etiological factors for the onset of stomal stenosis, and a number of procedures
      have been recommended for the surgical correction of such stenosis. STUDY DESIGN:
      A prospective analysis of 12 patients who underwent surgical correction of stomal
      stenosis is presented. METHODS: At the Institute of Clinical Otolaryngology we
      have recently defined a surgical technique for the correction of stomal stenosis
      that combines radial incisions, V-shaped flaps, and interposing flaps. This
      technique enables us to correct all the types of stenosis, and we have treated 12
      patients to date. RESULTS: To date, the average follow-up has been 17 months
      (range, 3-36 mo), and the results are encouraging. Early stenosis of the
      tracheostoma reappeared in one patient, who had successful repeat surgery with
      the same technique. CONCLUSIONS: Early results suggest the routine use of this
      surgical technique in the treatment of stomal stenosis.

PMID- 11568557
TI  - Adenovirus calcium phosphate coprecipitates enhance squamous cell carcinoma gene
      transfer.
AB  - OBJECTIVES/HYPOTHESIS: Adenoviral-mediated gene transfer offers a potential new
      treatment strategy for squamous cell cancer of the head and neck (SCCHN). Initial
      studies on some SCCHN cell lines have shown that these cells can be resistant to
      adenovirus-mediated gene transfer, requiring large amounts of vector and long
      infection times. The objectives of this study were to identify the barriers to
      gene transfer in three SCCHN lines, FaDu, SCC-9, and SCC-15, and to develop a
      method to circumvent the obstacles. We hypothesized that a low expression of
      adenovirus receptors may limit adenovirus infection and this may be overcome by
      using adenovirus complexed with calcium phosphate coprecipitates. METHODS: Using
      standard cell and molecular biology techniques, the infectability of SCCHN cells
      was investigated. RESULTS: Using Cy3-labeled adenovirus, we found minimal binding
      of adenovirus to FaDu cells and variable levels of binding among SCC-9 and SCC-15
      cells. Northern blot analysis indicated that messenger RNA (mRNA) transcripts for
      coxsackie-adenovirus receptor, which binds adenovirus, were absent in FaDu cells
      but present in SCC-9 and SCC-15 cells. Integrin alphavbeta5, which binds and
      facilitates internalization of adenovirus, were expressed at low levels in all
      three cell types. We overcame these barriers by using adenovirus complexed with
      calcium phosphate precipitates. Total transgene expression and the number of
      cells expressing transgene were increased in all three cancer lines using
      adenovirus complexed with calcium phosphate precipitates compared with adenovirus
      that was not complexed. CONCLUSIONS: Data in the present study suggest that
      adenovirus-mediated gene transfer to SCCHN cell lines is a result of limited
      viral receptors. Delivering adenovirus in a calcium phosphate coprecipitate
      enhanced gene transfer and, perhaps, the therapeutic index.

PMID- 11568556
TI  - Motility-related proteins as markers for head and neck squamous cell cancer.
AB  - HYPOTHESIS: Increased cell motility is a hallmark of cancer cells. Proteins
      involved in cell motility may be used as molecular markers to characterize the
      malignant potential of tumors. METHODS: Molecular biology and
      immunohistochemistry techniques were used to investigate the expression of a
      selected panel of motility-related proteins (Rho A, Rac 2, Cdc42, PI3K, 2E4, and
      Arp2) in normal, premalignant, and squamous cell cancer cell lines of human head
      and neck origin. To assess the clinical potential of these proteins as molecular
      markers for cancer, immunohistochemistry was performed on paraffin-fixed head and
      neck cancer specimens (n = 15). RESULTS: All six motility-associated proteins
      were overexpressed in the premalignant and squamous cell cancer cell lines
      relative to normal keratinocytes. Immunohistochemistry with Rho A and Rac 2
      showed increased staining in areas of cancer but not in normal tissue.
      CONCLUSION: Proteins involved in cell motility can be used as markers for head
      and neck squamous cell carcinoma. The head and neck cell lines used in this study
      may be used as a model to further investigate cell motility. Molecular markers of
      motility could have a significant impact on the diagnosis and staging of cancers
      originating from differentiated non-motile cells.

PMID- 11568558
TI  - Variability of genetic alterations in different sites of head and neck cancer.
AB  - OBJECTIVE: Tumors arising from different sites of the head and neck area have
      different clinical behavior. However, most of the studies on genetic alterations
      in head and neck squamous cell carcinomas do not make a distinction between the
      sites within this area. The objective of this study is to compare the genetic
      alterations in three different sites of the head and neck (larynx, oropharynx,
      and hypopharynx). STUDY DESIGN: Prospective study. METHODS: Thirty-eight
      laryngeal, 29 oropharyngeal, and 37 hypopharyngeal carcinomas were studied. DNA
      from tumor and healthy tissue was evaluated for amplification of the oncogenes at
      11q13 region (CCND1, FGF3, FGF4 and EMS1) and of the oncogenes MYC and ERBB1; for
      integration of the human papillomavirus (HPV) types 6b and 16; for loss of
      heterozygosity (LOH) at p53 and NAT2; and for the cellular DNA content. RESULTS:
      FGF3 and FGF4 showed a significantly higher frequency of amplification in
      hypopharyngeal tumors (P =.006 and P =.0002, respectively). CCND1 amplification
      had a nearly statistically significant (P =.072) higher frequency of
      amplification in hypopharyngeal tumors. Aneuploid tumors were found in a
      significantly lower proportion in the larynx (P =.03) compared with the other
      sites. For the other genetic alterations, no significant differences among the
      three sites were found. CONCLUSIONS: These results suggest that cancers
      originating from different sites in the head and neck may have different tumor
      biology. Therefore, they should be considered as different entities.

PMID- 11568559
TI  - The modified Lothrop procedure: lessons learned.

PMID- 11568560
TI  - Three-dimensional alloplastic orbital reconstruction in skull base surgery.

PMID- 11568561
TI  - The validity and reliability of the reflux finding score (RFS).
AB  - BACKGROUND: The evaluation of medical and surgical outcomes relies on methods of
      accurately quantifying treatment results. Currently, there is no validated
      instrument whose purpose is to document the physical findings and severity of
      laryngopharyngeal reflux (LPR). OBJECTIVE: To evaluate the validity and
      reliability of the reflux finding score (RFS). METHODS: Forty patients with LPR
      confirmed by double-probe pH monitoring were evaluated pretreatment and 2, 4, and
      6 months after treatment. The RFS was documented for each patient at each visit.
      For test-retest intraobserver reliability assessment, a blinded laryngologist
      determined the RFS on two separate occasions. To evaluate interobserver
      reliability, the RFS was determined by two different blinded laryngologists.
      RESULTS: The mean age of the cohort was 50 years (+/- 12 standard deviation
      [SD]). Seventy-three percent were women. The RFS at entry was 11.5 (+/- 5.2 SD).
      This score improved to 9.3 (+/- 4.7 SD) at 2 months, 7.3 (+/- 5.5 SD) at 4
      months, and 6.1 (+/- 5.2 SD) at 6 months of treatment (P <.001 with trend). The
      mean RFS for laryngologist no. 1 was 10.8 (+/- 4.1 SD) at the initial screening
      and 10.8 (+/- 4.0 SD) at the repeat evaluation (r = 0.95, P <.001). The mean RFS
      for laryngologist no. 2 was 11.1 (+/- 3.8 SD) at the initial screening and 10.9
      (+/- 3.7 SD) at the repeat evaluation (r = 0.95, P <.001). The correlation
      coefficient for interobserver variability was 0.90 (P <.001). CONCLUSIONS: The
      RFS accurately documents treatment efficacy in patients with LPR. It demonstrates
      excellent inter- and intraobserver reproducibility.

PMID- 11568562
TI  - Immediate percutaneous medialization for acute vocal fold immobility with
      aspiration.
AB  - OBJECTIVES: To determine the efficacy of immediate bedside or office
      percutaneous, trans-thyroidal injections of a bioabsorbable gelatin material
      (Gelfoam, Upjohn Co., Kalamazoo, MI) to decrease the risk of aspiration resulting
      from acute vocal fold immobility. STUDY DESIGN: Retrospective review of patients
      presenting with acute vocal fold immobility and aspiration or high aspiration
      risk at an urban, tertiary care university hospital. METHODS: All patients were
      evaluated by videostroboscopy, functional endoscopic evaluation of swallowing
      (FEES), and objective voice measures. Patients with acute vocal fold immobility
      and evidence of aspiration on history or FEES were given the option of
      medialization by Gelfoam injection. Injections were performed percutaneously in
      the office or at the bedside under laryngoscopic guidance. FEES was repeated
      after injection to verify improvement in aspiration. RESULTS: Eleven patients
      underwent Gelfoam injection for treatment of aspiration and vocal fold
      immobility. All were significantly improved on post-injection FEES study. All
      patients were returned to an oral diet, avoiding the need for long-term enteral
      access. CONCLUSION: Percutaneous Gelfoam injections is a rapid, temporary
      solution to the common problem of aspiration resulting from acute vocal fold
      immobility.

PMID- 11568563
TI  - Complications of type I thyroplasty and arytenoid adduction.
AB  - OBJECTIVES/HYPOTHESIS: Unilateral vocal fold paralysis resulting in glottal
      incompetence can cause significant morbidity attributable to impaired speech,
      swallowing, and ability to protect the airway. Type I thyroplasty in combination
      with arytenoid adduction is a proven technique for medialization of the paralyzed
      vocal fold but must be evaluated in light of potential complications following
      laryngeal framework surgery. STUDY DESIGN AND METHODS: The charts of 237 patients
      who underwent unilateral vocal fold medialization surgery between July 1, 1991,
      and August 30, 1999, at a tertiary care cancer referral center were
      retrospectively reviewed. RESULTS: There were 98 cases of type I thyroplasty
      alone and 96 cases of type I thyroplasty with arytenoid adduction. The two groups
      had similar patient characteristics. Mean time of surgery (45 vs. 73 min, P
      <.0001) and length of hospital stay (1.1 vs. 1.8 d, P <.0001) were increased when
      arytenoid adduction was performed. Overall improvement of symptoms was similar in
      both groups (93%-94%), but posterior glottic closure appeared subjectively
      improved when arytenoid adduction was used (P =.0054). Overall complication rates
      were slightly higher in the arytenoid adduction group (14% vs. 19%), primarily
      because of transient vocal fold edema and wound complications (9 vs. 19 cases),
      but the increase was not statistically significant (P =.1401). Complications
      warranting medical or surgical intervention occurred in 8% of cases. Two patients
      who underwent type I thyroplasty with arytenoid adduction required tracheotomy as
      a consequence of postoperative complications. The three patients who had
      extrusion of the implant underwent type I thyroplasty alone. CONCLUSION: Using
      the appropriate technique, the potential benefits of improved glottic function
      following type I thyroplasty with arytenoid adduction outweigh the small risk of
      significant complications observed.

PMID- 11568564
TI  - Microbiology of chronic frontal sinusitis.
AB  - OBJECTIVES: To determine bacterial and fungal organisms that are present in
      patients undergoing surgery for chronic frontal sinusitis. STUDY DESIGN:
      Retrospective, nonrandomized study. METHODS: Retrospective, nonrandomized
      bacterial and fungal cultures were performed on 46 sinus aspirates obtained by
      frontal sinus trephination performed on 30 consecutive patients with chronic
      frontal sinusitis. RESULTS: Six patients were having sinus surgery for the first
      time, 19 patients had undergone prior functional endoscopic sinus surgery without
      instrumentation of the frontal sinus/recess, and the third group included 5
      patients who had undergone prior frontal sinus/recess surgery. Preoperative
      computed tomography scan of the frontal sinuses revealed complete opacification
      in 63% (29/46 frontal sinuses) and partial opacification in 22% (10/46), and no
      data were available for 15% (7/46). Aerobic cultures revealed that 38% (13/35
      cultures) had no growth, 21% (7/35) grew Staphylococcus aureus, 21% (7/35) grew
      coagulase-negative Staphylococcus, 9% (3/35) grew Haemophilus influenzae, and 26%
      (9/35) grew a variety of other organisms. Anaerobic cultures were positive in 3%
      (1/32) of sinuses, and fungal cultures were positive in 4% (1/24). Haemophilus
      influenzae was most common in primary cases, whereas coagulase-negative
      Staphylococcus was most common in patients undergoing revision frontal sinus
      surgery. There were no other significant differences between cultures from
      patients undergoing revision frontal sinus surgery, revision functional
      endoscopic sinus surgery without prior frontal surgery, and primary surgery.
      CONCLUSIONS: This study suggests that organisms involved in chronic inflammatory
      disease of the frontal sinus may change after previous sinus surgery. The study
      failed to support a significant role for anaerobes. The role for coagulase
      negative Staphylococcus as a potential pathogen or a contaminating agent remains
      unclear.

PMID- 11568565
TI  - Comparison of antral tap with endoscopically directed nasal culture.
AB  - OBJECTIVES/HYPOTHESIS: The diagnosis of acute bacterial rhinosinusitis continues
      to generate controversy in critically ill patients. The efficacy of
      endoscopically directed cultures in these patients is unknown. We compared antral
      tap (AT) with endoscopic tissue culture (ETC) of the osteomeatal complex in an
      intensive care unit (ICU) setting. METHODS: Twenty patients admitted to a
      surgical/trauma ICU were evaluated by AT and ENB for the presence of
      rhinosinusitis. All patients had 1) a fever of unknown origin without resolution
      on empiric antibiotic therapy for > or =48 hrs; 2) other sources of fever ruled
      out; 3) computed tomography scan evidence of mucoperiosteal thickening +/- sinus
      air/fluid levels; and 4) attempt at conservative treatment with topical
      decongestants and removal of all nasal intubation. Microbiologic data were
      collected and analyzed for any statistical difference between groups. RESULTS: A
      total of 29 sides underwent simultaneous tap and endoscopically directed tissue
      culture. The mean age was 40 years (range, 23-77 y) with 85% being males. Fifteen
      of 20 (75%) patients in the AT group were culture-positive. Of the 49 isolates
      from the AT, 55% yielded Gram-negative bacilli (Acinetobacter sp. 37%) and 45%
      yielded Gram-positive cocci. The ETC group was culture-positive in 18 of 20 (90%)
      patients. Of the 52 isolates from the ETC, Gram-negative bacilli were found in
      58% (Acinetobacter sp. 33%) and 42% yielded Gram-positive cocci. The ETCs were
      culture-positive in all but 1 patient with positive taps. There appeared to be a
      concordance between AT and ETC in 60% of the patients. In five instances (25%),
      results of the AT or ETC changed ICU management. Two patients ultimately required
      sinus surgery. CONCLUSIONS: Sinus taps and/or endoscopically directed tissue
      cultures led to a change in ICU care in 25% of ICU patients studied. In patients
      with fever of unknown origin and computed tomography evidence of sinusitis, an
      antral tap continues to provide important information concerning maxillary
      sinusitis. However, ETC may give as good a representation of the microbiology and
      secondary inflammatory changes responsible for bacterial ICU rhinosinusitis
      causing fever of unknown origin. Further study on a larger group of patients is
      needed.

PMID- 11568566
TI  - Sinusitis complicated by meningitis: current management.
AB  - OBJECTIVES: Meningitis is the most common intracranial complication of sinusitis.
      We review the incidence, current management, outcomes, and complications of this
      serious infection. Our study also examines the evolving roles of endoscopic sinus
      surgery and other new therapeutic and diagnostic modalities in our armamentarium.
      STUDY DESIGN: A retrospective chart review was performed at a tertiary academic
      medical center of all patients diagnosed with sinusitis with complications
      between January 1985 and December 1999. METHODS: The patients were divided into
      two main groups: intracranial versus orbital complications. Meningitis was the
      most common intracranial complication. Data on patients with sinusitis and
      meningitis were collected and analyzed. RESULTS: Intracranial complications were
      present in 39 of 82 patients whereas orbital complications were noted in 43
      patients. Twenty-one of the 39 intracranial complications were meningitis. The
      most common computed tomography finding in adults (54%) was sphenoid sinusitis.
      All patients with AIDS (6 of 21) had unique cryptococcus meningitis. In patients
      without AIDS, the most common organism was Streptococcus pneumoniae (10 of 21).
      The most common sequela was seizure disorder (4 of 21). Endoscopic sinus surgery
      was performed on 7 of 21 patients. One patient with AIDS who had sinusitis and
      meningitis died. CONCLUSIONS: Meningitis as a complication of sinusitis may still
      pose a serious threat. Although outcomes are encouraging, sequelae such as
      seizure disorders and hearing loss are common complications. The introduction of
      high-resolution computed tomography scans and magnetic resonance imaging and the
      availability of wide-spectrum antibiotics have improved our management
      significantly.

PMID- 11568568
TI  - Post-tonsillectomy bleeding: a meta-analysis.
AB  - OBJECTIVE/HYPOTHESIS: To reconcile conflicting reports and opinions of the value
      of preoperative coagulation studies for patients undergoing tonsillectomy. STUDY
      DESIGN: Meta-analysis: Articles were identified by MEDLINE search, references
      from review articles, textbook chapter, and retrieved reports. Independent
      observers selected prospective trials of patients undergoing tonsillectomy or
      adenoidectomy and tonsillectomy. Retrospective studies meeting other inclusion
      and exclusion criteria were included for sensitivity analyses of results.
      METHODS: Data were abstracted from studies for an end point of bleeding with
      normal and abnormal coagulation tests. Four prospective studies met all inclusion
      and exclusion criteria. These four studies were used in the data synthesis. An
      additional eight retrospective studies met all other criteria and were used in
      the sensitivity analysis. RESULTS: Pooled analysis of 3384 patients revealed a
      rate of 3.3% (95% confidence interval [CI], 2.5%-4.1%) for post-tonsillectomy
      bleeding in patients with normal coagulation studies. A rate of 8.7% (95% CI,
      1.5%-15.9%) was obtained for bleeding in patients with abnormal coagulation
      studies. No significant rate difference in post-tonsillectomy bleeding was
      demonstrated. CONCLUSION: There is no difference in the rate of post
      tonsillectomy bleeding in patients with abnormal coagulation studies as compared
      with patients with normal coagulation studies obtained preoperatively.

PMID- 11568567
TI  - Transtympanic versus sustained-release administration of gentamicin: kinetics,
      morphology, and function.
AB  - OBJECTIVES/HYPOTHESIS: Transtympanic gentamicin therapy has become a popular
      treatment modality for Meniere's disease, but questions regarding the ideal dose
      of medicine, the best administration paradigm, and the safest treatment end-point
      remain unanswered. The goal of this study is to examine the inner ear kinetics of
      transtympanic gentamicin and compare this with the kinetics of sustained-release
      delivery in a basic science model. In addition, we plan to examine the
      relationship of these kinetics curves to the effect of the two treatment
      modalities on inner ear function and morphology. It is hoped that this analysis
      will help clinicians to better apply local medical therapy to the ear. STUDY
      DESIGN: The study is a basic science project designed to examine perilymph
      gentamicin concentrations, hearing results, and inner ear morphology in an animal
      model. METHODS: Gentamicin was applied to the right ear of chinchillas either
      through a transtympanic approach or in a sustained-release device. The left ear
      remained untreated as an internal control. At set time points the animals'
      hearing and balance function was studied and the perilymph was harvested, after
      which the animal was killed and preserved for histological evaluation. Kinetics
      curves were constructed for each of the two treatment paradigms and compared with
      histological and functional outcomes. RESULTS: The two groups yielded
      dramatically different kinetics curves. The transtympanic curve had a high peak
      level at 24 hours with rapid fall-off and almost total elimination by 48 hours,
      whereas the sustained-release curve was characterized by a long, flat plateau
      phase with a peak that was approximately one-third that of the transtympanic
      curve. In addition, the variability seen in perilymph concentrations was
      significantly higher in the transtympanic group than in the sustained-release
      group. Immunohistochemical analysis using antibodies against cleaved caspase-3
      and cleaved caspase-7 demonstrated early damage in the spiral ganglion of both
      groups, before any obvious morphological change in the hair cells. The staining
      was significantly more dense in animals with transtympanic delivery. Cochlear and
      vestibular hair cell damage was seen at late time points in animals from both
      groups. Hearing loss (HL) progressed in an orderly fashion in the sustained
      release group of animals, with no HL seen in the early time points and universal
      significant threshold shifts present by 72 hours. In the transtympanic group, the
      HL was more variable, with significant threshold shifts occurring as early as 4
      hours after treatment, but with some animals demonstrating preserved hearing at
      the 72-hour time point. All animals demonstrated profound HL at the 6-day time
      point. CONCLUSIONS: There is a significant difference in the shape and
      variability of the perilymph kinetics curve when comparing sustained-release
      delivery to transtympanic delivery of gentamicin. High early peak levels of
      gentamicin seen with transtympanic therapy may have a profound effect on the
      spiral ganglion and produce early HL before obvious hair cell damage. Sustained
      delivery of gentamicin produces universal HL at 72 hours. The reliability of
      sustained-release delivery to the ear reduces functional and morphological
      variations between animals.

PMID- 11568569
TI  - Base-of-tongue cancer: survival, function, and quality of life after external
      beam irradiation and brachytherapy.
AB  - OBJECTIVE: Base-of-tongue cancer has traditionally been treated by surgical
      resection followed by radiation therapy. Primary radiation therapy with
      brachytherapy has recently been proposed as an alternative. In a prior analysis,
      we found that patients with advanced tongue-base cancer treated by total
      glossectomy and postoperative radiation therapy can be cured while potentially
      maintaining good quality of life. Therefore, we designed the current study to
      assess survival, function, and quality of life in our patients with tongue-base
      cancer who were treated with primary radiation therapy and brachytherapy with
      neck dissection as indicated. STUDY DESIGN: Consecutive case series. METHODS:
      Twenty patients were treated between 1993 and 1997 using the approach just named.
      The T stages were T1 (3), T2 (10), T3 (6), and T4 (1). The N stages were N0 (3),
      N1 (3), N2 (11), and N3 (3). At the time of brachytherapy catheter placement,
      neck dissections were performed in all 14 patients with N2 or N3 disease.
      Surviving patients completed a functional status survey and quality of life
      questionnaire. RESULTS: The 3- and 5-year Kaplan-Meier corrected actuarial
      survival rates were 57% and 38%, respectively. Eight patients remained alive at
      the time of this writing and completed the functional status survey and quality
      of life assessment. Function and quality of life were well maintained in patients
      treated with external-beam irradiation followed by brachytherapy and neck
      dissection. However, none of our patients with T3 disease had long-term survival.
      CONCLUSION: Although we do not endorse external-beam irradiation and
      brachytherapy for advanced tongue-base cancers, this treatment should be strongly
      considered for patients with T1 or T2 tumors in whom preservation of function and
      quality of life is a priority.

PMID- 11568570
TI  - Use of low-dose technetium Tc 99m sulfur colloid to locate sentinel lymph nodes
      in melanoma of the head and neck: preliminary study.
AB  - OBJECTIVES/HYPOTHESIS: Because sentinel lymph nodes are the first lymph nodes
      that drain a primary cancer site, results of sentinel lymph node (SLN) biopsy
      indicate status of the regional lymph nodes. Preoperative lymphoscintigraphy and
      intraoperative combined application of the handheld gamma probe and blue-dye
      technique (i.e., the "combined technique") was used previously to accurately
      identify the SLN, mostly in melanoma of the extremities and trunk and, sometimes,
      in melanoma of the head or neck, which is anatomically complex. Because of this
      complexity, melanoma in the head or neck is inherently problematic to treat:
      Localization of the SLN can be difficult or impossible because the primary cancer
      site can be near or overlapping the nodal basin. The objective of the present
      study was to determine the technical modifications and other considerations that
      can make SLN localization feasible in cases of melanoma occurring near or
      overlapping the nodal basin in the head or neck. STUDY DESIGN/METHODS: In a
      retrospective study of clinical records containing our database of melanoma
      diagnoses made between January 1996 and December 1999, we identified 27 patients
      diagnosed with stage I or II primary melanoma of the head or neck with clinically
      negative neck nodes who also had had preoperative lymphoscintigraphy. Of the 27
      patients (17 male and 10 female patients; mean age, 54 y), 24 had SLN biopsy by
      intraoperative localization using both the handheld gamma probe and the blue-dye
      technique. RESULTS: Among the 27 patients who had SLN mapping, a median Breslow
      thickness of 1.8 mm was noted. Sentinel lymph node was noted at preoperative
      lymphoscintigraphy in 26 (96%) of the 27 patients. Activity of technetium Tc 99m
      (Tc-99m) sulfur colloid injected ranged from 10 to 1000 microCi (0.37 to 37
      megabecquerel [MBq]). Intraoperative use of the combined technique for sentinel
      lymphadenectomy was successful in 92% of patients. Sentinel lymph nodes were
      identified in all 14 patients who received Tc-99m sulfur colloid at an activity
      level less than 60 microCi (2.2 MBq); mean activity level of injected TC-99m
      sulfur colloid was 28 microCi (1.04 MBq). Sentinel lymph nodes were identified in
      8 (80%) of 10 patients who received Tc-99m sulfur colloid at an activity level
      greater than 100 microCi (3.7 MBq); mean activity of injected Tc-99m sulfur
      colloid in these patients was 482 microCi (17.8 MBq). A mean number of 1.4
      sentinel lymph nodes per patient was identified at preoperative
      lymphoscintigraphy, and a mean number of 3 sentinel lymph nodes per patient was
      identified intraoperatively using the combined technique. Tumor recurrence was
      seen in 2 (10%) of the 19 patients who had cancer-free SLN at mean follow-up of
      18 months (range, 1 to 47 mo). Sentinel lymphadenectomy of the parotid region did
      not injure the facial nerve in any patients. CONCLUSIONS: For patients with
      primary melanoma that is near or overlaps the nodal basin in the head or neck,
      SLN biopsy can be accurately performed using Tc-99m sulfur colloid at low
      activity levels (10 microCi to 60 microCi [0.37 to 2.2 MBq]. However, background
      radiation from the primary injection site can incorporate the SLN, making
      localization at preoperative lymphoscintigraphy difficult if not impossible;
      therefore, the high doses commonly used for melanoma of the extremities and trunk
      (500 to 2000 microCi [18.5 to 74 MBq]) should not be used for melanoma of the
      head or neck if the primary site is near or overlaps the nodal basin. In
      addition, absorption of Tc-99m sulfur colloid by salivary glands increases
      background radiation in the nodal basin; therefore, use of the handheld gamma
      probe for intraoperative localization of SLN can be problematic in regions where
      lymph nodes are adjacent to or within the substance of the salivary gland (i.e.,
      the submandibular and parotid glands).

PMID- 11568571
TI  - Molecular differences in mucoepidermoid carcinoma and adenoid cystic carcinoma of
      the major salivary glands.
AB  - OBJECTIVE/HYPOTHESIS: Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma
      (ACC), the most common malignancies of the major salivary glands, are clinically
      and pathologically different. To determine whether MEC and ACC have different
      molecular characteristics, we examined the expression of erbB-2, erbB-3,
      epidermal growth factor receptor (EGFR), and transforming growth factor-alpha
      (TGF-alpha), important molecular features in other malignancies. STUDY
      DESIGN/METHODS: Archival tissue sections of 22 MEC and 6 ACC tumors of the major
      salivary glands were evaluated immunohistochemically for expression of erbB-2,
      erbB-3, EGRF, and TGF-alpha. A differential immunostaining score, reflecting the
      difference in immunostaining between carcinoma and uninvolved salivary gland
      tissue, was calculated for cytoplasmic and membranous staining. RESULTS: Positive
      immunostaining for all biomarkers was observed in the cytoplasm and membrane of
      both tumors. However, expression was higher in MEC than in ACC tumors and was
      statistically significant for cytoplasmic EGFR (P =.009), TGF-alpha (P =.041),
      and membranous EGFR (P =.004). A significantly higher percentage of MEC cells
      also demonstrated positive immunostaining for cytoplasmic erbB-3 (P =.022), EGFR
      (P =.005), membranous erbB-3 (P =.022), and EGFR (P =.013). The differential
      immunostaining score was significantly higher for MEC compared with uninvolved
      alveolar tissue and the membranes of uninvolved ductal tissue. There were no
      statistically positive differential immunostaining scores for ACC. CONCLUSIONS:
      There is a clear difference in the molecular phenotypes of MEC and ACC. The lack
      of statistically significant expression in ACC, when compared with similar
      uninvolved salivary gland tissue, suggests minimal involvement for these
      molecular structures in the pathogenesis of ACC. Conversely, erbB-2, erbB-3,
      EGFR, and TGF-alpha may have a role in the development and progression of MEC.
      These results have therapeutic implications for MEC of the major salivary glands.

PMID- 11568572
TI  - Quality of life after treatment for advanced laryngeal and hypopharyngeal cancer.
AB  - OBJECTIVES: To compare health-related quality of life measures after treatment
      for advanced (stages III and IV) laryngeal and hypopharyngeal cancers. STUDY
      DESIGN: Retrospective chart review and patient response to Health Status
      Questionnaire-12 (HSQ-12). METHODS: Our study included 54 patients identified
      from the Tumor Registry of the University of Louisville Brown Cancer Center who
      were diagnosed and treated between 1995 and 2000. Demographics, tumor data, and
      treatment information were obtained from the Tumor Registry database.
      Questionnaires were mailed to all patients and included telephone follow-up.
      Comparative data and responses were analyzed for the 24 patients who responded to
      the survey. RESULTS: Fifteen patients were treated with chemotherapy and
      radiation therapy (CRT). Six patients underwent surgery with postoperative
      radiation therapy (SRT). The remaining three patients were treated with radiation
      therapy but were not used in this analysis. The average follow-up was 35 months
      after treatment. The CRT and SRT groups were statistically similar regarding age,
      sex, duration of follow-up, tumor grade, and tumor stage. Laryngeal primary
      tumors were more common in the SRT group than in the CRT group (P =.005). Eight
      domains were assessed by the HSQ-12: physical functioning, role-physical, bodily
      pain, health perception, energy/fatigue, social functioning, role-mental, and
      mental health. No statistical differences were found between the CRT and SRT
      groups, except for role limitations attributable to physical health (P =.007).
      CONCLUSIONS: These results indicate that only one of eight domains differs
      significantly between treatment groups when using the HSQ-12. Two-year survival
      end-point analysis of global health assessment may represent a simplified and
      meaningful way to compare treatment modalities in patients with advanced-stage
      head and neck cancer.

PMID- 11568573
TI  - Complementary and alternative medicine in otolaryngology.
AB  - The widespread interest in and use of complementary and alternative medicine
      (CAM) by patients in the United States has been established by multiple surveys.
      One-third of the U.S. population uses some form of CAM, and an estimated 23
      billion dollars is spent annually on these therapies. Because of prevalent usage
      of CAM among patients, it is important that physicians have some knowledge of
      this subject. With this purpose in mind, this report reviews the current research
      on CAM as it relates to common disorders of the head and neck: rhinitis,
      sinusitis, tinnitus, vertigo, and head and neck oncology.

PMID- 11568574
TI  - A large arteriovenous malformation of the external ear in an adult: report of a
      case and approach to management.
AB  - OBJECTIVES/HYPOTHESIS: Arteriovenous malformations involving the external ear are
      relatively uncommon in adults. Arteriovenous malformations in the head and neck
      can poses difficult therapeutic challenges. STUDY DESIGN: Case report. METHODS:
      We report a case of a large arteriovenous malformation in the external ear in a
      41-year-old man. RESULTS: Extensive enlargement of the previously latent and
      asymptomatic arteriovenous malformation was triggered by blunt trauma to the ear.
      CONCLUSION: We discuss the definition, clinical findings, diagnostic approaches,
      and therapeutic management of arteriovenous malformations.

PMID- 11568575
TI  - An evolution in the management of sinonasal inverting papilloma.
AB  - OBJECTIVE: We reviewed the 15-year experience of our institution (Medical College
      of Wisconsin, Milwaukee, WI) in managing sinonasal inverting papilloma, examining
      trends in diagnosis and treatment. STUDY DESIGN: Retrospective. METHODS: Thirty
      seven patients with inverting papilloma were treated from 1986 to 1999.
      Demographic data, clinical presentations, pathological findings, surgical
      approaches and procedures, and recurrence rates were collected retrospectively.
      Each lesion was categorized into one of four groups based on computed tomography
      scans and endoscopic findings. This categorization was developed to compare
      various surgical approaches for tumors in each group. RESULTS: Thirty-one
      patients had complete information for inclusion in our study. Nineteen patients
      were treated endoscopically with an average follow-up of 50 months. Eight
      patients were in group I, five were in group II, six were in group III, and no
      patients were in group IV. The recurrence rate for the endoscopic group was 10%.
      Twelve patients underwent lateral rhinotomy or sublabial degloving approach with
      an average follow-up of 58 months. Five patients were in group I, three patients
      were in group II, 1 patient was in group III, and three patients were in group
      IV. The recurrence rate for the external group was 8%. Difference in recurrence
      rates (P =.85) was not observed between the endoscopic and external approach
      groups. Regardless of approach, patients who had primary resection had a
      recurrence of 0%, whereas those with secondary resection had a recurrence of 17%
      (P =.10). CONCLUSIONS: Technological advancements have led to a trend of
      detecting sinonasal inverting papilloma before extension beyond the sinonasal
      region. Difference in recurrence rates was not observed between the endoscopic
      and the external approach groups. Recurrence rates are lower for primary
      resection versus secondary resection, regardless of surgical approach.

PMID- 11568576
TI  - Inverted papilloma: a review of 53 cases.
AB  - OBJECTIVE: To assess the surgical management of patients with inverted nasal
      papilloma over a 14-year period. STUDY DESIGN: Retrospective study. SETTING:
      Tertiary health care center. RESULTS: Fifty-three patients (38 males, 15 females)
      with an average age of 49.8 years were treated. Overall recurrence rate was 28%
      and a malignant association of 9% was shown. Recurrence rates varied from 27% in
      patients with more extensive disease involvement treated by lateral rhinotomy and
      medial maxillectomy, to 30% in patients with less extensive disease treated
      conservatively. Of the 5 patients with associated malignancy, 3 (6% of all
      patients) are likely to have undergone malignant transformation. CONCLUSION:
      Aggressive initial management remains the therapeutic aim in this condition.

PMID- 11568577
TI  - Anterior and posterior medialization (APM) thyroplasty.
AB  - OBJECTIVE: In unilateral vocal fold paralysis with dysphonia, most of the
      paralyzed vocal folds may be medialized effectively by medialization
      laryngoplasty. However, if the posterior glottal gap is wide, these procedures
      may sometimes have a limit to medialize the posterior glottis and cannot be
      effective for acceptable voice quality. The objective of this study is to
      introduce a new surgical technique for medializing the membranous and
      cartilaginous portions of the paralyzed vocal fold: anterior and posterior
      medialization (APM) thyroplasty. METHOD: Six patients underwent APM thyroplasty.
      They completed preoperative and postoperative evaluation with acoustic analysis
      and video laryngoscopy. RESULTS: All patients satisfied their voice subjectively
      after surgery. The paralyzed vocal folds, membranous and cartilaginous parts,
      were medialized well, and the paralyzed arytenoid showed less anterior tipping
      postoperatively. On voice analysis all patients showed prolonged phonation times
      and decreased perturbations after surgery. CONCLUSION: The advantages of this
      procedure are to medialize the membranous and cartilaginous portions of the
      paralyzed vocal fold directly and to correct vertical mismatch between two vocal
      folds. This procedure might be especially indicated in the lateralized position
      of the paralyzed vocal fold but not in the higher paralyzed vocal fold compared
      with the normal vocal fold.

PMID- 11568578
TI  - Surgical management of retropharyngeal space infections in children.
AB  - OBJECTIVE: To study the perioperative management strategies in a large group of
      pediatric patients undergoing surgical therapy for suppurative adenitis of the
      parapharyngeal and retropharyngeal spaces. STUDY DESIGN: Retrospective analysis
      of all patients treated surgically from January 1, 1989, to December 31, 1998, in
      a tertiary care pediatric hospital. METHODS: Charts were reviewed for demographic
      data, duration and nature of symptoms, radiological workup, surgical approach,
      complications, duration of medical therapy and antibiotic choice, and
      bacteriological findings. Computed tomography (CT) results were correlated to
      surgical findings. RESULTS: A dramatic increase in the incidence of deep neck
      space infection was seen during the study period; this increase was congruent
      with the increase in culture-positive group A beta-hemolytic streptococcal
      abscesses. More than two-thirds of the patients were boys with the peak incidence
      being in the 3- to 5-year-old group. The duration of symptoms before presentation
      was less than might be expected, especially in the younger age groups. Seventy of
      73 children were treated with a transoral approach. Sixty-eight of 73 were
      successfully treated with one operative intervention. Irregularity of the abscess
      wall was found to be a stronger predictor of the presence of pus than the
      presence of ring enhancement. CONCLUSIONS: The current study represents the
      largest series of pediatric retropharyngeal abscesses in the modern medical
      literature. Changes in the disease process and in management from the first half
      of the century to today are reviewed, and recommendations for optimal management
      presented. The data in this series support a transoral approach to these
      abscesses unless there is extension lateral to the great vessels.

PMID- 11568579
TI  - Tonsillectomy with argon plasma coagulation (APC): evaluation of pain and
      hemorrhage.
AB  - OBJECTIVE: Argon plasma coagulation (APC) offers a new possibility for
      tonsillectomy (TE) because of its effective hemostasis and limited penetration
      depth of the coagulation zone. The APC dissector allows dissection and hemostasis
      in a one-step procedure. The aim of this prospective, randomized, single-blinded
      study was the evaluation of pain and hemorrhage of the "hot" argon-plasma
      coagulation tonsillectomy (TE(APC)) compared with a conventional "cold" non
      electrosurgery tonsillectomy (TE(Conv)). METHODS: Two hundred one consecutive
      patients undergoing tonsillectomy were included in a single-blinded, randomized,
      prospective study with stratification in two age groups. RESULTS: There was no
      statistical significant difference between TE(APC) and TE(Conv) in the intensity
      of postoperative pain and primary or secondary hemorrhage in both age groups. In
      the TE(APC) group, the mean duration of tonsillectomy was significantly reduced
      by more than 50% in both age groups (P <.01). The blood loss was 90% decreased in
      the TE(APC) compared with the TE(Conv) in both age groups (P <.01). CONCLUSIONS:
      The APC technique does not face the general problem of electrosurgery or thermal
      coagulation techniques in which the postoperative pain is often increased
      compared with conventional cold techniques. It offers an innovative new
      tonsillectomy method with significant reduced blood loss and surgical time.

PMID- 11568580
TI  - Sclerotherapy with picibanil (OK-432) for congenital lymphatic malformation in
      the head and neck.
AB  - HYPOTHESIS/OBJECTIVES: Congenital lymphatic malformations of the head and neck
      (LMHN) present special challenges to the otolaryngologist-head and neck surgeon.
      Recently, a number of sclerotherapy trials have shown promising results. In this
      study, we present our experiences with picibanil (OK-432) sclerotherapy for this
      lesion. STUDY DESIGN: Retrospectively review. METHODS: We retrospectively
      reviewed 21 patients who have undergone sclerotherapy with picibanil for LMHN.
      RESULTS: Satisfactory response with complete or nearly complete shrinkage of the
      lesions was observed in 15 cases after repeated sclerotherapy (average, two
      times). We did not observe any significant morbidity or complications in the
      patients treated with picibanil. Reduction in size of the mass was achieved in
      weeks to months. Some of the patients who had not had any other previous
      treatment showed remarkable reductions in size even after the first therapy. When
      we used picibanil sclerotherapy as a primary treatment for the LMHN, most of our
      patients showed satisfactory results regardless of the size or location of the
      lesions. CONCLUSION: Given with our experience and the reports that failure of
      picibanil sclerotherapy does not hinder subsequent surgical salvage procedures,
      we recommend trying picibanil sclerotherapy as a primary treatment for the LMHN
      and performing surgical excision as a secondary modality if the response to the
      sclerotherapy is not satisfactory.

PMID- 11568581
TI  - Prognostic factors in major salivary gland cancer.
AB  - OBJECTIVE: To identify features of major salivary gland cancers that are
      prognostic for disease-free survival. STUDY DESIGN: A retrospective study of 78
      patients with major salivary gland cancer (64 parotid and 14 submandibular gland)
      who underwent surgery for definitive treatment from 1976 to 1996. A select group
      of patients also received adjuvant radiation (56%) and/or chemotherapy (13%).
      METHOD: Clinical and pathological risk factors were obtained from patients'
      charts and pathology reports. Age, gender, tumor site, T-stage, facial paralysis,
      histologic neck involvement, perineural invasion, and cancer grade were analyzed
      with respect to disease-free survival. The role of adjuvant treatment in terms of
      clinical outcome was also investigated. RESULTS: In our series, the 5-year
      disease-free survival was 65%. Examining clinical and histologic features one at
      a time, we found poorer prognosis was associated with submandibular tumors
      compared with parotid (P =.02), higher T-stage (P =.001), positive cervical nodes
      (P <.001), perineural invasion (P =.002), and high-grade or adenoid cystic tumors
      (P =.002). A multivariable analysis indicated that positive lymph nodes (P =.07)
      and perineural invasion (P =.03) were important histologic predictors of shorter
      disease-free survival. Receipt of both adjuvant radiation and cisplatin-based
      chemotherapy (P =.05) was an independent predictor of longer disease-free
      survival. CONCLUSION: Our study indicated that the presence of positive lymph
      nodes and perineural invasion is important independent predictors of disease-free
      survival. Our limited data also suggest that adjuvant chemotherapy and radiation
      therapy may improve disease-free survival.

PMID- 11568583
TI  - In vivo diagnosis of nasopharyngeal carcinoma using contact rhinoscopy.
AB  - OBJECTIVES: To evaluate the potential use of contact endoscopy for the diagnosis
      of nasopharyngeal carcinoma (NPC). STUDY DESIGN: Prospective study to examine the
      nasopharynx of 30 patients with nasopharyngeal carcinoma and 18 subjects with
      normal nasopharynx in a clinic setting using contact rhinoscopes (Karl Storz,
      Tuttlingen, Germany, 7215 AA, 00 and 7215 BA, 300; 23 cm long; 4 mm in diameter).
      METHODS: The superficial cells of the normal nasopharynx and the nasopharyngeal
      tumors were stained with 1% methylene blue and examined with contact rhinoscopes
      at high magnifications (x 60 and x 150). The areas under examination were then
      biopsied. The contact endoscopic images were compared with the corresponding
      hematoxylin and eosin-stained histologic sections of the biopsied tissues.
      RESULTS: Sixty-six procedures were performed in 48 patients. The images of normal
      pseudostratified ciliated epithelium and squamous epithelium were readily
      recognized by contact endoscopy in all subjects with normal nasopharynx (10 men
      and 8 women; mean age, 51.9 y). Twenty-six of 30 patients with NPC (86.6%; 18 men
      and 8 women; mean age, 50.6 y) were successfully examined by contact endoscopy
      under local anesthesia. In these 26 patients, two patterns of malignant cells
      were identified with contact endoscopy. The patterns of contact endoscopic images
      corresponded well with the histologic findings. CONCLUSION: Contact endoscopy is
      an accurate and reliable office-based procedure, which allows for in-vivo
      diagnosis of nasopharyngeal carcinoma.

PMID- 11568582
TI  - A prospective study of quality of life in head and neck cancer patients. Part II:
      Longitudinal data.
AB  - OBJECTIVES: To evaluate the health-related quality of life (HRQL) of patients
      with head and neck cancer during and after treatment with radiotherapy, surgery,
      and chemotherapy. STUDY DESIGN: Prospective, descriptive study. METHODS: All new
      patients in four institutions in Norway and Sweden were asked to participate.
      Health-related quality of life was assessed at baseline and at 1, 2, 3, 6, and 12
      months after start of treatment by means of the European Organization for
      Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and
      the EORTC head and neck cancer-specific questionnaire. Baseline results are
      described elsewhere; longitudinal results are presented in the current article.
      Three hundred fifty-seven patients with cancer in the oral cavity, pharynx,
      larynx, nose, sinuses, and salivary glands and neck node metastases from unknown
      primaries filled in the questionnaires at baseline. RESULTS: Seventy-eight
      percent of the patients who were alive after 12 months filled in all
      questionnaires (218/280). The general trend was that HRQL deteriorated
      significantly during treatment, followed by a slow recovery until the 12-month
      follow-up with few exceptions (senses, dry mouth, and sexuality). Patients who
      later died reported worse HRQL at each assessment point compared with patients
      who filled in all six questionnaires, whereas those who dropped out of the study
      for other reasons were quite similar to patients who filled in all
      questionnaires. The patients with pharyngeal cancer in general reported worse
      HRQL compared with the other groups and did not reach pretreatment values in
      several domains. Stage was also an important factor for HRQL in patients with
      head and neck cancer. CONCLUSION: Detailed knowledge about the differences
      between groups and changes over time may aid us in the communication with
      patients and in the design of intervention studies focusing on improvement of the
      support and rehabilitation of patients with head and neck cancer.

PMID- 11568584
TI  - All-trans-retinoic acid enhances the effect of adenovirus-mediated wild-type p53
      gene transfer in head and neck squamous cell carcinoma.
AB  - OBJECTIVES: Adenovirus-mediated p53 (AdCMVp53) gene therapy for cancer is
      currently undergoing phase III clinical trials. One problematic aspect of this
      therapy is that the current protocols result in low transduction of the
      therapeutic virus in vivo. To search new modalities that can enhance the effect
      of AdCMVp53 gene therapy, we focused on retinoids. METHODS: To study the effect
      of ATRA in combination with AdCMVp53 gene therapy, we pretreated head and neck
      squamous cell carcinoma (HNSCC) cells for 72 hours with a low-dose All-trans
      retinoic acid (ATRA) (10-7 M-10-8 M) which will not affect the in vitro cell
      growth, and then infected the cells with low MOI (30MOI) AdCMVp53. In vitro cell
      proliferation assays, cell cycle assays were performed. Expression of p53 and p53
      related gene products, BAX and p21, were examined. RESULTS: The combined
      treatment with ATRA and Ad-p53 suppressed cell growth and induced apoptosis
      significantly more than AdCMVp53 treatment alone (P <.05). p53 expression
      significantly increased more after the combined treatment than after either
      treatment alone, at both the transcription and protein levels. In addition,
      increased expression of p21 and BAX, which are downstream gene products of p53,
      was observed in the combination. ATRA also enhanced the expression of green
      fluorescent protein (GFP) transduced by an adenovirus-cytomegalovirus (CMV)-GFP
      vector suggesting ATRA enhances adenovirus-CMV-promoted vectors through
      transcription. CONCLUSIONS: Our results indicate that ATRA enhances AdCMVp53
      expression through transcriptional mechanisms and can synergistically induce
      apoptosis in HNSCC cells. ATRA has a potential to enhance the effect of
      adenovirus-mediated p53 gene therapy for HNSCC.

PMID- 11568585
TI  - Expression of p16, nm23-H1, E-cadherin, and CD44 gene products and their
      significance in nasopharyngeal carcinoma.
AB  - OBJECTIVE: The present study was aimed to determine whether p16/MTS1, nm23-H1, E
      cadherin, and CD44 proteins were expressed in nasopharyngeal carcinoma (NPC) and
      whether those expressions were pathologically significant in the progress of NPC.
      METHOD: We examined non-cancerous nasopharyngeal mucosa (20 cases) and NPC (80
      cases) using immunohistochemistry with six different types of monoclonal
      antibodies against p16, nm23-H1, E-cadherin, CD44H, CD44v3, and CD44v6 proteins.
      RESULTS: The results showed that 1) the rates of positive p16 protein expression
      and of preserved E-cadherin protein expression in NPC were significantly lower
      than those in non-cancerous tissue (P <.01); 2) no significant difference in the
      rate of positive expression of nm23-H1, CD44H, CD44v3, and CD44v6 proteins were
      observed between non-cancerous nasopharyngeal mucosa and NPC; 3) no significant
      difference in the expression of those proteins were found by respective
      correlation analyses of sex, stage, and size of primary tumor in NPC; and 4) no
      significant difference in the rates of positive expression of CD44H, CD44v3, and
      CD44v6 proteins were observed in NPC between with and without lymph node
      metastasis, indicating that those gene products did not correlate with lymph node
      metastasis in NPC. However, there were inverse correlations between the
      expression of p16, nm23-H1, or E-cadherin protein and lymph node metastasis (P
      <.05), indicating that the expression of p16, nm23-H1, and E-cadherin gene were
      related to the carcinogenesis and tumor progression of NPC. CONCLUSION: Detecting
      the expressions of those gene products may provide clinically valuable
      information for therapeutic strategy and for predicting the prognosis of patients
      with NPC.

PMID- 11568586
TI  - Dendritic cells pulsed with apoptotic squamous cell carcinoma have anti-tumor
      effects when combined with interleukin-2.
AB  - OBJECTIVES: Dendritic cells, the most potent of the antigen-presenting cells,
      have been widely studied as a promising tool for antitumor immunotherapies.
      However, little has been determined about the efficacy of dendritic cell-based
      therapy for the treatment of squamous cell carcinoma (SCC) because there are no
      known SCC-specific antigens. Recent reports indicate that dendritic cells can
      acquire antigens in the form of apoptotic cells and induce cytotoxic T-lymphocyte
      responses. The aim of this study was to test the feasibility of adoptive
      dendritic cell immunotherapy against SCC by using apoptotic tumor cells as a
      source of tumor antigens. STUDY DESIGN: A poorly immunogenic SCC line KLN 205 was
      used to make subcutaneous tumors on the flank of DBA2/J syngeneic mice. Bone
      marrow-derived dendritic cells were pulsed with ultraviolet B-irradiated
      (apoptotic) KLN 205 cells in vitro and transferred to the opposite flank
      subcutaneously. Some of the animals received simultaneous intraperitoneal
      injections of low-dose interleukin-2. RESULTS: When combined with interleukin-2,
      adoptive transfers of dendritic cells that were pulsed with apoptotic SCC
      significantly suppressed the tumor growth (P <.001) without notable side effects.
      Splenic T cells of treated mice produced greater amounts of interferon-gamma when
      restimulated with the relevant tumor (P <.001) as compared with control groups,
      indicative of an effective T-cell-mediated systemic immune response. CONCLUSION:
      Adoptive transfer of dendritic cells pulsed with apoptotic tumor cells as a
      source of tumor antigens, can elicit effective antitumor responses in the poorly
      immunogenic SCC model when combined with interleukin-2.

PMID- 11568587
TI  - Evaluation of inlay butterfly cartilage tympanoplasty: a randomized clinical
      trial.
AB  - OBJECTIVES/HYPOTHESIS: In 1998 Eavey described a new inlay technique for
      tympanoplasty in the pediatric age group using a cartilage graft through a
      transcanal approach. This technique was found to be effective and comfortable (no
      external canal incisions or ear packing). This study evaluated the efficacy of
      modified-inlay cartilage tympanoplasty compared with the conventional underlay
      tympanoplasty. STUDY DESIGN: Randomized clinical trial. METHODS: Patients were
      enrolled from December 1998 to March 2000. Seventy tympanoplasties were done in
      adults with medium-sized tympanic membrane (TM) perforations: 34 inlay
      tympanoplasties and 36 underlay tympanoplasties (control group). The main outcome
      measures were the "take rate" on the 30th postoperative day and the audiometric
      result at the second postoperative month. Secondary outcome measures include
      subjective postoperative hearing, postoperative pain, duration of surgery, and
      cost of the procedures. RESULTS: The "take rate" did not differ between groups on
      the 30th postoperative day (88.2% in the inlay tympanoplasty group vs 86.1% in
      the underlay tympanoplasty group; P =.8). After a mean follow-up of 7.5 +/- 3.8
      months (range, 3-16 mo), the "take rate" was 85.3% in the inlay tympanoplasty
      group and 83.3% in the underlay tympanoplasty group (P =.8). In the inlay
      tympanoplasty group there was closure of the air-bone gap (ABG) to within 10 dB
      in 64.7% and to within 20 dB in 94.1%. The corresponding numbers to underlay
      tympanoplasty were 75% and 97.2%. In only 2 cases (5.9%) in the inlay
      tympanoplasty group and in 1 case (2.8%) in the underlay tympanoplasty group the
      ABG was greater than 20 dB. No audiometric difference was observed between groups
      (P =.6). Most patients in the inlay tympanoplasty group reported immediate
      improvement in their hearing (P <.0001). Pain was reported by 10 patients in the
      inlay tympanoplasty group and by 30 patients in the underlay tympanoplasty group
      on the first postoperative day (P <.0001). The duration of the surgery (mean +/-
      standard deviation) was 33.6 +/- 7.8 minutes for the inlay tympanoplasty group
      and 62.9 +/- 12.7 minutes for the underlay tympanoplasty group (P <.0001). The
      estimated charge for inlay tympanoplasty at our institution was 65% less
      expensive than underlay tympanoplasty. CONCLUSION: The "take rate" and
      audiometric results following inlay cartilage tympanoplasty or underlay
      tympanoplasty were similar. Inlay butterfly cartilage tympanoplasty did not
      require general anesthesia, was less expensive, and more comfortable to the
      patient.

PMID- 11568588
TI  - Management of chronic otitis media with effusion: the role of glutathione.
AB  - BACKGROUND: The inflammatory cells documented in chronic otitis media with
      effusion (OME) spontaneously release oxidants which can induce middle ear (ME)
      epithelial cell damage. Glutathione (GSH), a major extracellular antioxidant in
      humans, plays a central role in antioxidant defense. PURPOSE: To evaluate the
      effects of GSH treatment on chronic otitis media with effusion (OME). SUBJECTS
      AND INTERVENTION: Sixty children with chronic OME were enrolled, 30 of whom were
      randomly assigned to the treatment group and 30 to the placebo group. Patients in
      the treatment group received 600 mg glutathione in 4 mL saline per day subdivided
      into five 2-minute administrations given by nasal aerosol every 3 or 4 waking
      hours for 2 weeks. Patients in the control group received 4 mL saline per day
      following the same procedure as for GSH treatment. RESULTS: Three months after
      therapy improvement had occurred in 66.6% of patients in the GSH-treated group
      and in 8% of the control subjects (P <.01). CONCLUSION: On the basis of these
      results, GSH treatment could be considered for the nonsurgical management of
      chronic OME.

PMID- 11568589
TI  - Role of clonazepam in the treatment of idiopathic downbeat nystagmus.
AB  - OBJECTIVE/HYPOTHESIS: Downbeat nystagmus is defined as spontaneous nystagmus
      present with fixation in the primary position or lateral gaze. Those who have
      downbeat nystagmus but negative magnetic resonance imaging results are termed as
      idiopathic. Patients with idiopathic downbeat nystagmus, although unconcerned
      with their etiology, have visual symptoms such as oscillopsia, diplopia, or
      blurred vision. The purpose of this study is to evaluate the efficacy of
      clonazepam in treating idiopathic downbeat nystagmus. METHODS: Patients with
      downbeat nystagmus were rechecked by electronystagmography (ENG); then 0.5 mg
      clonazepam was administered orally. One hour later, follow-up ENG was performed
      again to evaluate the evolution of the downbeat nystagmus. If the test was
      effective, then 1.0 mg clonazepam twice daily was administered to the patients.
      RESULTS: Seven cases had downbeat nystagmus, including idiopathic in five,
      cerebellar degeneration in one, and cerebellopontine angle tumor in one. The
      efficacy rate for the clonazepam test was 100% in five cases of idiopathic
      downbeat nystagmus, whereas it was ineffective in the case of cerebellar
      degeneration. After long-term therapy with clonazepam, all patients with
      idiopathic downbeat nystagmus experienced elimination of oscillopsia, relief of
      diplopia, and improvement of visual acuity. Although temporary relief of downbeat
      nystagmus was observed 1 hour after the clonazepam test, downbeat nystagmus was
      not eliminated permanently. CONCLUSION: We recommend long-term therapy by
      clonazepam with a dosage of 1.0 mg twice daily in cases of idiopathic downbeat
      nystagmus. Reducing the downbeat nystagmus as well as eliminating the oscillopsia
      can be anticipated.

PMID- 11568590
TI  - Powered instrument papilloma excision: an alternative to laser therapy for
      recurrent respiratory papilloma.

PMID- 11568591
TI  - Saddle blanket graft tympanoplasty and lateral attic wall reconstruction for
      defects produced by primary acquired cholesteatoma.

PMID- 11568592
TI  - Stabilization of autograft ossicles in type III tympanoplasty.

PMID- 11568593
TI  - Fine-needle aspiration biopsy.
AB  - OBJECTIVES: Fine-needle aspiration biopsy (FNAB) is a technique in which a fine
      needle is introduced into a mass, cellular material is aspirated, and a
      cytological diagnosis is rendered. It separates reactive and inflammatory
      processes that do not require surgical intervention from neoplasia and benign
      from malignant tumors. FNAB lends itself to the diagnosis of palpable head and
      neck masses, in particular, those that persist following antibiotic treatment.
      STUDY DESIGN/METHODS: This clinical state-of-the-art review article is intended
      to provide an overview of the clinical use of FNAB in the management of head and
      neck masses. Relevant case histories are used to illustrate this point. RESULTS:
      Fine-needle aspiration biopsy has a high overall diagnostic accuracy of 95% for
      all head and neck masses, 95% for benign lesions, and 87% for malignant ones.
      CONCLUSIONS: There are virtually no contraindications, and complications are
      minimal. Advantages of FNAB are that it is safe and simple, it can be performed
      as an outpatient procedure, and it is well tolerated by patients. In the present
      managed care environment, it also proves cost-effective. The diagnosis is readily
      known to the clinician, and appropriate treatment modalities can be discussed
      with the patient. It is recommended as a first line of investigation in palpable
      head and neck masses.

PMID- 11568595
TI  - Preoperative differences between male and female patients with sleep apnea.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the differences between female and male
      patients with obstructive sleep apnea syndrome (OSAS) in the preoperative period.
      STUDY DESIGN: Nonrandomized cross-sectional study. METHODS: An analysis of 686
      patients (111 women and 575 men) with OSAS was completed. Multivariate modeling
      techniques were employed to correlate gender with the preoperative respiratory
      disturbance index (RDI), apnea index (AI), hypopnea index (HI), body mass index
      (BMI), age, and initial symptoms. RESULTS: At presentation, the male patients
      were significantly younger and had a lower BMI and a higher RDI and AI than the
      female patients. For the entire OSAS population studied, the RDI increased as the
      BMI increased (correlation coefficient [r] = 0.35, P = <.001). For the female
      patients there was a weaker correlation (r = 0.21, P =.034), and in male patients
      there was a stronger correlation (r = 0.40, P <.001). For the entire population
      there was a negative correlation between age and RDI (r = -0.15, P <.001). In
      female patients there was a nonsignificant correlation (r = -0.09, P =.35), and
      in male patients the correlation was significant (r = -0.16, P <.001). There was
      no difference in the reporting of the number of symptoms based on gender (P
      =.355). Female patients noted headaches on awakening more commonly than male
      patients (P =.001), and male patients noted snoring (P =.014) and stopping
      breathing during sleep (P =.001) more often than female patients. CONCLUSIONS:
      The analysis demonstrated that within a surgical population sample, gender
      differences exist. The findings of this series were as follows: 1) Apnea severity
      in women was less weight-dependent than in men; (2) in men there was a
      significant negative correlation between age and apnea severity; and (3) female
      and male patients reported the same number of signs or symptoms on presentation,
      although certain signs and symptoms were more commonly reported based on gender.
      Current clinical evaluation practices must take into account this gender
      disparity.

PMID- 11568596
TI  - Feasibility and outcome of endoscopic staple-assisted esophagodiverticulostomy
      for Zenker's diverticulum.
AB  - OBJECTIVES/HYPOTHESIS: Endoscopic staple-assisted esophagodiverticulostomy (ESED)
      is a newly described method of surgically correcting Zenker's diverticulum.
      Initial reports on the ease and success of the surgery have been quite
      enthusiastic, making it seem the procedure of choice. We initiated the procedure
      in an algorithm of treatment of Zenker's diverticulum, to further explore the
      feasibility and outcome of this new technique. STUDY DESIGN: This is a case
      series of 23 patients with Zenker's diverticulum who have undergone surgical
      repair. For each patient, an attempt at ESED was made. If unsuccessful, an open
      approach was then taken. RESULTS: Seven of 23 patients (30%) were unable to be
      treated with ESED because of inability to expose the diverticulum or unfavorable
      anatomy of the diverticulum itself. Of the remaining 16 patients, ESED was
      successful in resolving the symptoms of diverticulum in 14 (87%). Two patients
      (13%) were somewhat improved but had persistent dysphagia. No significant
      complications occurred. All patients resumed oral diet within the first 24 hours
      after surgery. CONCLUSION: Esophagodiverticulostomy is an excellent method of
      surgically correcting Zenker's diverticulum in many patients, but anatomical
      considerations may prevent its use, making open approaches of continued
      importance in a surgeon's armamentarium.

PMID- 11568597
TI  - Recurrence and its avoidance in juvenile angiofibroma.
AB  - OBJECTIVE: Angiofibroma is a highly vascular lesion for which a wide range of
      surgical approaches has been recommended. Irrespective of the approach, a
      significant and often rapid recurrence rate is reported in all major series. AIM:
      To consider the impact of lessons learned from imaging on the recurrence rate of
      angiofibroma. MATERIAL AND METHODS: From a cohort of 90 male patients with
      histologically proven angiofibroma, 40 individuals were studied. The recurrence
      rate in 20 cases treated before March 1998 was compared with that in 19 cases
      treated thereafter. In the latter group, an additional exploration of the
      basisphenoid had been undertaken. RESULTS: The two cohorts were comparable in age
      range (7-27 y and 11-24 years, respectively), and all had been treated by
      midfacial degloving. In the first group, 8 recurrences occurred which were
      multiple in 1 patient. In the next 19 patients, the area of the pterygoid canal
      was meticulously explored and the basisphenoid drilled to remove all residual
      tumor. No recurrences have occurred in this group during a follow-up of between 6
      months to 3 years. CONCLUSION: Meticulous removal of angiofibroma infiltrating
      the pterygoid canal and basisphenoid is paramount to avoid "recurrence."

PMID- 11568598
TI  - Use of helium-oxygen mixtures to relieve upper airway obstruction in a pediatric
      population.
AB  - OBJECTIVES: Helium as a component of inspired gas decreases turbulent flow and
      airway resistance. Helium-oxygen mixtures have been used since the 1930s in the
      management of patients with upper airway obstruction. The objective of this study
      was to evaluate the efficacy of helium-oxygen mixtures in relieving upper airway
      obstruction in a pediatric population. STUDY DESIGN: Retrospective chart review
      of 42 pediatric patients who received helium-oxygen mixtures for upper airway
      obstruction within a 3-year period. METHODS: The study protocol included 42
      pediatric patients, aged 1 week to 14 years, who were admitted to the Children's
      Hospital of Philadelphia from June 1997 to December 2000 and who received a total
      of 44 treatments of helium-oxygen therapy for upper airway obstruction. Response
      to treatment was determined by reduction in work of breathing noted on the chart.
      RESULTS: Thirty-two of 44 helium-oxygen treatments resulted in a positive
      response (73%). There were no significant differences in demographic
      characteristics between responders and nonresponders, except all of the premature
      infants were responders and 6 of the 9 patients with syndromes were
      nonresponders. CONCLUSIONS: Helium-oxygen therapy is a useful adjunct therapy for
      upper airway obstruction. Controlled clinical trials are necessary to better
      define the appropriate settings for use of helium-oxygen.

PMID- 11568599
TI  - Pediatric autoimmune neuropsychiatric disorders and streptococcal infections:
      role of otolaryngologist.
AB  - OBJECTIVE: To increase awareness and understanding of the putative role of
      streptococcal infection in the development of neuropsychiatric disorders in
      children and to discuss therapeutic options in this group of patients. METHODS:
      Case illustration and literature review. RESULTS: Two siblings, one with
      obsessive-compulsive disorder (OCD) and one with a tic disorder, had
      tonsillectomy for recurrent streptococcal pharyngitis. At the latest follow-up
      visit (11 mo postoperatively), both patients exhibited significant improvement in
      their psychiatric illnesses. We discuss these cases as well as the diagnosis,
      pathophysiology, and treatment of pediatric autoimmune neuropsychiatric disorders
      associated with streptococcal infections (PANDAS). CONCLUSION: PANDAS is an
      active area of research investigating the relationship between streptococcal
      infections and the development of obsessive-compulsive disorder or tic disorders
      (or both) in children. The etiopathogenesis of PANDAS is thought to reflect
      autoimmune mechanisms and involvement of the basal ganglia of susceptible hosts.
      Because otolaryngologists evaluate a large portion of pediatric patients with
      recurrent streptococcal pharyngitis, it is important to be aware of this
      association and to manage these patients appropriately.

PMID- 11568600
TI  - Tympanic membrane grafting with alloderm.
AB  - OBJECTIVE/HYPOTHESIS: The purpose of this work is to evaluate the performance of
      an acellular dermal allograft (AlloDerm; LifeCell Corp., The Woodlands, TX) in
      tympanic membrane (TM) grafting. STUDY DESIGN: A retrospective review of 20
      consecutive tympanoplasty surgeries using temporalis fascia and 20 consecutive
      procedures using AlloDerm. METHODS: The charts of 20 consecutive adults who
      underwent tympanoplasty surgery were reviewed to evaluate graft take and hearing
      results. Similarly, 20 consecutive patients who had TM grafting with AlloDerm
      were reviewed. Pre- and postoperative air-bone gaps (ABG) at 500 Hz, 1000 Hz,
      2000 Hz, and 4000 Hz were compared. RESULTS: There were no graft failures in
      either the temporalis fascia group or the AlloDerm group. No statistically
      significant difference was noted in hearing results when comparing the residual
      conductive loss in both postoperative groups. CONCLUSIONS: AlloDerm is a suitable
      material for TM grafting. This product is especially valuable in revision surgery
      in which the availability of appropriate autologous grafting material is limited.

PMID- 11568601
TI  - Predicting fall risks in an elderly population: computer dynamic posturography
      versus electronystagmography test results.
AB  - OBJECTIVES/HYPOTHESIS: Falls are the leading cause of morbidity and mortality for
      persons aged 65 years and older, with more than 2 million people falling and
      sustaining serious injury annually. This study compared computer dynamic
      posturography (CDP) and electronystagmography (ENG) results as predictors of
      falls. STUDY DESIGN: Retrospective. METHODS: Thirty-three patients over the age
      of 65 years who presented to a balance disorders and falls prevention clinic were
      used for this study (22 women and 11 men, with an average age of 78.0 y and a
      mean fall rate of 3.5 times). All had experienced at least one fall in the year
      before visiting the clinic and were tested with both CDP and ENG. The CDP results
      were divided into subcategories (sensory organization testing and limits of
      stability); ENG results were divided into four categories (ocular motor,
      rotational chair, positional, and caloric studies). RESULTS: Test findings were
      classified as normal or abnormal based on age-matched normative data. Of the
      patients in the study, 27.3% were normal for one type of testing and abnormal for
      the other. Twenty-six patients (78.8%) had abnormal results on CDP, and 20
      individuals (60.6%) showed ENG abnormalities (42.4% for ocular motor, 28.6% for
      positional, 13.6% for caloric, and 11.2% for rotational chair studies). The
      limits of stability category was significant in predicting multiple falls.
      CONCLUSION: For this population, CDP was determined to be a more sensitive test
      for identifying patients who have fallen, with limits of stability testing the
      most significant part of the CDP battery; for ENG studies, the best falls
      indicator was the ocular motor battery.

PMID- 11568602
TI  - Management of nasopharyngeal salivary gland malignancy.
AB  - OBJECTIVE: The objective of this study was to evaluate the oncological outcome
      and complication rate following surgical treatment of nasopharyngeal salivary
      gland malignancy. STUDY DESIGN: Retrospective case review at tertiary care skull
      base center. METHODS: Pertinent medical records were reviewed from 23 patients
      presenting with minor salivary gland malignancy. Clinical presentation, prior
      treatment, histological type and grade, clinical stage, details of surgical
      treatment, and postoperative adjuvant radiation therapy were studied. Survival
      and recurrence data were analyzed using the Kaplan-Meier and Cox proportional
      hazards methods. RESULTS: Histological types included 11 adenoid cystic
      carcinomas, 8 mucoepidermoid carcinomas, and 4 cases of adenocarcinoma not
      otherwise specified. All patients underwent primary surgical resection, and the
      lateral infratemporal middle fossa approach was used in 20 patients. Prior
      radiation therapy had been administered in 6 patients who presented for treatment
      of recurrent disease, and the remaining 17 patients underwent planned
      postoperative radiation therapy. Elective neck dissection was undertaken in 15
      patients, and occult neck disease was present in 47%. Disease specific survival
      was 67% at 5 years and 48% at 10 years. High-grade tumors had a significantly
      poorer outcome (P =.035) with a relative risk of 4.6 compared with low-grade
      disease. Local control was seen to be 77% at 5 years. CONCLUSIONS: Planned
      combined surgery and radiation therapy achieves survival outcomes and recurrence
      rates in nasopharyngeal salivary gland malignancy comparable to results reported
      using the same treatment for minor salivary gland tumors cancer originating
      elsewhere in the head and neck. Because of the high rate of occult neck
      metastases, we recommend elective neck dissection as part of the surgical
      treatment with this disease entity. The lateral infratemporal middle fossa
      approach provides safe and adequate access to resect the vast majority of these
      tumors with acceptable complication rates. A reliable form of vascularized
      reconstruction is necessary to prevent serious postoperative complications, and
      we currently prefer the gastro-omental free flap.

PMID- 11568603
TI  - Spectral karyotyping analysis of head and neck squamous cell carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: The genetic content of head and neck squamous cell
      carcinomas is ill defined. Spectral karyotyping (SKY) is a new technique that
      allows the simultaneous detection of all chromosomal translocations by labeling
      each individual chromosome with different fluorescent agents. In the current
      study we used SKY to analyze cell lines and a primary tumor derived from head and
      neck squamous cell carcinomas (HNSCC) to delineate recurrent translocations and
      breakpoints. STUDY DESIGN: Spectral karyotyping analysis of head and neck cancer.
      METHODS: Two cell lines (MDA886 and MSK922) and one primary tumor in short-term
      culture were subjected to metaphase growth arrest with colcemide in their
      exponential growth phase and fixed onto glass slides. Painting probes for each of
      the autosomes and the sex chromosomes were generated from flow-sorted human
      chromosomes using sequence-independent DNA amplification. The probes were labeled
      using a polymerase chain reaction-based reaction and hybridized to metaphase
      preparations for 2 days at 37 degrees C. Biotinylated probes were detected using
      avidin Cy5 and digoxigenin-labeled probes with an anti-mouse digoxigenin antibody
      followed by goat anti-mouse antibody conjugated to Cy5.5. Chromosomes were
      counterstained with 4,6-diamino-2-phenyliodole (DAPI), and a minimum of five
      metaphases were captured and analyzed for each case. Breakpoints on the SKY
      painted chromosomes were determined by comparison of corresponding DAPI banding.
      RESULTS: Spectral karyotyping analysis revealed a complex pattern of chromosomal
      abnormalities. A total of 66 translocations were identified in the three cases,
      with one new recurrent translocation at (der(4)t(4;20)(q35;?)). Nine complex
      translocations, involving three or more chromosomes, were identified in these
      cases. Overall, 96 breakpoints were assigned to metaphase chromosomes and another
      74 breakpoints could not be assigned. Breakpoints most commonly involved
      chromosomes in genetic rearrangements were 1, 3, 5, 8, 13, 16, and 17.
      CONCLUSIONS: Spectral karyotyping analysis reveals the true complexity of
      chromosomal aberrations in cell lines derived from head and neck squamous cell
      carcinomas. The use of SKY, in combination with other techniques, may allow for a
      more complete assessment of the genetic abnormalities of head and neck cancers
      and serve as a starting point for gene identification.

PMID- 11568604
TI  - Functional outcomes after supracricoid laryngectomy.
AB  - OBJECTIVES: Local control and 5-year survival rates are similar for patients
      undergoing total laryngectomy and supracricoid laryngectomy for the treatment of
      advanced-stage laryngeal carcinoma. However, comprehensive studies of functional
      outcomes after supracricoid laryngectomy are lacking. STUDY DESIGN: Cohort study.
      METHODS: This investigation provides objective voice laboratory data, skilled
      listener impressions of voice samples, swallowing evaluations, and patient self
      perceptions of speech ability obtained from 10 supracricoid laryngectomees.
      RESULTS: Results demonstrated variable acoustic and speech aerodynamic
      disturbances, hoarse-breathy vocal quality, and speech dysfluency. Patients' self
      perceptions of voice revealed severe dysphonia that induced certain emotional,
      physical, and functional setbacks. However, blinded judges rated these
      individuals as possessing intelligible speech and communication skills. All
      patients demonstrated premature spillage of the bolus and varying degrees of
      laryngeal penetration, aspiration, and retention during swallowing studies.
      However, each patient used a compensatory strategy to protect the airway. Voice
      and swallowing abilities appeared to depend on the mobility of the arytenoid
      cartilages, base of tongue action, and residual supraglottic tissue for the
      creation of a competent neoglottal sphincter complex that vibrated during
      phonation efforts and protected the airway during deglutition. CONCLUSIONS:
      Supracricoid laryngectomy avoids the potential complications, limitations, and
      emotional problems associated with a permanent tracheostoma. All patients
      demonstrated intelligible voice and effective swallowing function
      postoperatively, supporting supracricoid laryngectomy as a suitable alternative
      surgical approach to the total laryngectomy in select patients.

PMID- 11568605
TI  - Hodgkin's and non-Hodgkin's lymphoma of the head and neck.
AB  - OBJECTIVES/HYPOTHESIS: Lymphomas are a frequent cause of malignant
      lymphadenopathy in the head and neck. This study was performed to evaluate the
      head and neck manifestations of lymphomas and to emphasize the different
      presentations of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). STUDY
      DESIGN: Retrospective review. METHODS: A retrospective review was made of all
      cases of lymphomas involving the head and neck at Marshfield Clinic (Marshfield,
      WI) between 1988 and 1996. Specifically, the clinical presentations, staging, and
      prognosis for HD and NHL with head and neck involvement were sought. RESULTS:
      Three hundred eleven patients were included in the study, 76 with HD and 235 with
      NHL. The median age at diagnosis for patients with HD was 27.7 years, and for
      patients with NHL, 67.2 years. This difference was highly significant (P <.001).
      No significant difference in gender was noted, with male patients occurring in
      59% with HD and 49% with NHL (P=.135). Extranodal involvement including the oral
      cavity, oropharynx, nasopharynx, paranasal sinuses, and larynx occurred with HD
      in 3 patients (4%) and with NHL in 54 patients (23% P <.001). Cervical adenopathy
      consisted of a single node in 24% of patients with HD and 33% of those with NHL
      (no significant difference, P=.236). The difference in mediastinal nodal
      involvement was highly significant, occurring in 65% of patients with HD and 38%
      of patients with NHL(P <.001). Abdominal nodes occurred in 20% of cases of HD and
      45% of cases of NHL (P<.001). A significant difference in constitutional symptoms
      was noted with 41% of cases in HD and 27% of cases in NHL (P=.020). For the
      percentage of patients with stage IV disease, there was a highly significant
      difference by diagnosis with 10% in HD and 36% in NHL (P <.001). The median
      follow-up time was 51 months, and 12% of patients with HD and 41% of patients
      with NHL died of their disease. Both the overall survival and survival from death
      attributable to disease were significantly better for HD(P<.001). CONCLUSIONS:
      Hodgkin's disease presents at a younger age and is less common than NHL. Cervical
      lymphadenopathy is the most common head and neck presentation for both diseases.
      Associated mediastinal adenopathy was more common with HD, and abdominal
      adenopathy with NHL. Constitutional symptoms were more common with HD. More
      advanced disease with a decreased overall survival was seen with NHL.

PMID- 11568606
TI  - Intraoperative magnetic resonance imaging for skull base surgery.
AB  - OBJECTIVES/HYPOTHESIS: Skull base surgery has evolved over the past several
      decades. Major improvements in the imaging of skull base pathology led to better
      target localization and better surgical planning. The objectives of this study
      were to assess the use of intraoperative magnetic resonance (MR) imaging in the
      management of a series of patients with skull base pathology. We hypothesized
      that high-quality intraoperative MR imaging would have an impact on surgery in
      this patient group. STUDY DESIGN: Prospective, non-randomized, cohort study.
      METHODS: Thirty-one patients with skull base lesions underwent surgery in a 1.5
      Tesla intraoperative MR suite. The concepts of a moving magnet, high magnetic
      field strength, and radiofrequency coil design are presented. RESULTS: Eleven of
      31 patients had the course of surgery significantly altered by the information
      acquired from the images obtained during surgery. CONCLUSIONS: Intraoperative MR
      imaging is a valuable adjunct to skull base surgery. One third of patients had
      altered surgery as a result of this adjunct. Intraoperative MR imaging is of
      particular value in the treatment of pituitary adenomas and benign skull base
      tumors.

PMID- 11568607
TI  - Parathyroid cysts: diagnosis and management.

PMID- 11568608
TI  - Water-jet dissection in parotid surgery: an experimental study in dogs.
AB  - OBJECTIVE: The objective of the present study was to investigate the application
      of the water-jet dissection method in parotid surgery by way of animal
      experiments, paying particular attention to the clinical and histological
      reactions of the facial nerve. STUDY DESIGN: An animal experimental study.
      METHODS: Total bilateral parotidectomies with retention of the facial nerve were
      performed on 19 beagle dogs by means of the Hydro-Jet device (Andreas Pein
      Medizintechnik Company, Schwerin, Germany) using different jet diameters and
      operating pressures. All operations were performed with continuous intraoperative
      facial monitoring (Neurosign 100, Inomed Company, Teningen, Germany). The dogs
      were monitored postoperatively over an average period of 20.3 days (range, 14-35
      d). Local findings and facial nerve status were documented daily. In a second
      phase, the dissected nerves were resected and the animals were killed. Samples of
      water-jet-dissected parotid tissue, as well as all dissected nerve branches,
      underwent histological examination and were compared with clinical and
      electrophysiological findings. RESULTS: It was possible to perform operations
      easily on all parotid glands by means of the Hydro-Jet using the small, 120
      microm jet at operating pressures of 40 to 60 bar and to dissect the facial nerve
      quickly and safely with retention of its functional capability (n = 34). The
      dissection of nerves using larger-diameter jets (150 and 200 microm [n = 64])
      resulted in a total of two reversible and seven irreversible partial pareses.
      CONCLUSIONS: The study has shown that it is possible to perform tissue-selective
      operations on the parotid gland by means of the Hydro-Jet using the 120-microm
      jet at operating pressures of 40 to 60 bar, ensuring safe, atraumatic dissection
      of the facial nerve with retention of its functional capability. The advantages
      of the new Hydro-Jet method offer a valuable alternative compared with the normal
      dissection methods adopted in parotid surgery. Thus the results of the present
      investigation currently are being checked within the framework of a clinical
      study at our clinic.

PMID- 11568609
TI  - Microinvasive Nd:YAG laser therapy of early glottic carcinoma and its effect on
      soluble interleukin-2 receptor, interleukin-2, and natural killer cells.
AB  - OBJECTIVE: To investigate the effectiveness of microinvasive Nd:YAG laser therapy
      in human glottic Tis and T1 carcinomas, as well as its effect on the cellular
      immune function of the tumor-bearing hosts. STUDY DESIGN: We treated 34 patients
      with microinvasive Nd:YAG laser therapy and evaluated its effect on the cellular
      immune function of the host. METHODS: Thirty-four patients with glottic Tis or T1
      squamous cell carcinoma were treated with fiberoptic laryngoscopic Nd:YAG laser
      surgery. Both before and after therapy, serum levels of soluble interleukin-2
      receptor (SIL-2R) and interleukin-2 (IL-2), as well as natural killer (NK) cell
      activity, were determined by means of double-antibody sandwich technique,
      tritiated thymidine-deoxyribonucleoside incorporation, and iodine 125-uridine
      deoxyribonucleoside release technique, respectively. RESULTS: All 34 patients
      tolerated the procedure well. A 3- to 7-year follow-up in a subgroup of 27
      patients resulted in an estimated cure rate of 85.2% (23 of 27 patients). In all
      27 patients with a regular follow-up, a subjective improvement of phonation was
      noted after therapy to various degrees. In 74% (20 of 27 patients), voice and
      speech subjectively recovered to almost normal levels. The post-therapy serum
      levels of SIL-2R were significantly declined (P <.001), whereas those of IL-2 and
      the NK activity were significantly elevated (P <.001) as compared with those
      detected before therapy. CONCLUSIONS: Therapy with fiberoptic laryngoscopic
      Nd:YAG laser surgery is simple, safe, effective and only minimally invasive for
      patients with glottic Tis or T1 carcinoma. At the same time, it has an
      immunoenhancing effect on its host.

PMID- 11568611
TI  - Long-term results of inferior turbinate reduction with argon plasma coagulation.
AB  - OBJECTIVES: Surgical reduction of the inferior turbinates is a commonly used
      therapy in patients with hyperplastic inferior turbinates when medical management
      remains ineffective. Current surgical methods have disadvantages (e.g., necessity
      of nasal packing, extended postoperative swelling, and high costs). Theoretical
      considerations render argon plasma coagulation (APC) a promising new therapeutic
      approach. STUDY DESIGN: In a prospective study, 121 patients with chronic nasal
      obstruction were treated for inferior turbinate reduction with APC. Hyperplasia
      of the nasal turbinates was diagnosed rhinoscopically and endoscopically and
      confirmed rhinomanometrically. The mean follow-up period was 12 months, ranging
      from 10 to 16 months. The treatment results were evaluated by a questionnaire,
      rhinomanometric findings, and electron microscopic studies of the nasal mucosa.
      In 50 patients a ciliary function test was performed preoperatively and
      postoperatively. METHODS: Argon plasma coagulation, a high-frequency
      electrosurgery, has been used for volume reduction of the inferior turbinate in
      local anesthesia. RESULTS: Seventy-six percent of the patients reported an
      improvement of the postoperative swelling within the first week. After 6 weeks,
      macroscopically the turbinates were re-epithelialized by normal mucosa in 63% of
      the patients. Electron microscopic studies after 3 months verified normal cilia.
      After 12 months, 83% of the patients stated that they had a better nasal airflow
      than preoperatively. Crust formation was minimal. No bleeding or impaired ciliary
      function occurred. Ninety-five percent of the patients were willing to undergo
      the same operation again. CONCLUSION: The long-term results have proved APC to be
      an effective and easy-to-perform alternative for inferior turbinate reduction
      with comparable results to other established surgical methods.

PMID- 11568610
TI  - Mutation and abnormal expression of the fragile histidine triad gene in
      nasopharyngeal carcinoma.
AB  - OBJECTIVE: To determine alterations of fragile histidine triad (FHIT) gene in
      nasopharyngeal carcinoma and the correlation of FHIT gene with nasopharyngeal
      carcinogenesis. STUDY DESIGN: Prospective study. METHODS: A total of 28
      nasopharyngeal carcinoma and 16 normal nasopharyngeal epithelium specimens were
      examined for abnormalities of FHIT gene by nested reverse-transcriptase
      polymerase chain reaction and DNA sequencing. RESULTS: The deletion of FHIT gene
      was not observed in 16 normal nasopharyngeal epithelium specimens. In 28 cases of
      nasopharyngeal carcinoma tissues, 12 (42.9%) exhibited FHIT aberrant transcripts.
      Complementary DNA sequencing revealed exonic deletion, small DNA insertion,
      synonymous mutation in exon 8, or frameshift mutation in exon 5. CONCLUSIONS: The
      present results suggest that the FHIT gene may play an important role in the
      pathogenesis of nasopharyngeal carcinoma and may be one of the candidate tumor
      suppressor genes in nasopharyngeal carcinoma.

PMID- 11568612
TI  - Surgical anatomy of the natural ostium of the sphenoid sinus.
AB  - OBJECTIVES: This study was undertaken to measure the distance and the angle
      between the anterior part of nasal cavity and the natural ostium of the sphenoid
      sinus. The anatomical location of the natural ostium according to the direction
      of surgeon's operating view toward the anterior wall of the sphenoid sinus was
      also analyzed. STUDY DESIGN: This study used careful cadaver dissection under a
      surgical microscope. METHODS: One hundred sagittally sectioned adult cadaveric
      heads were used. We measured the distances and angles for identifying the natural
      ostium of the sphenoid sinus using several reference points such as the limen
      nasi, the sill, and the posteroinferior end of the superior turbinate. In
      addition, we tried to identify whether the location of the natural ostium is
      medial or lateral to the posterior end of the superior turbinate. RESULTS: The
      natural ostium of the sphenoid sinus was located at an angle of 35.9 degrees with
      a distance of 56.5 mm from limen nasi and at an angle of 34.3 degrees with a
      distance of 62.7 mm from nasal sill. It was located approximately 1 cm above the
      posteroinferior end of the superior turbinate and at a medial aspect to the
      posterior end of the superior turbinate in 83% of specimens. CONCLUSIONS: We
      speculate that the posteroinferior end of the superior turbinate is the best
      landmark for identifying the natural ostium of the sphenoid sinus. Furthermore,
      the natural ostium should ideally be searched from a superior and medial aspect
      in relation to the posteroinferior end of the superior turbinate.

PMID- 11568613
TI  - Nasal nitric oxide and the nasal cycle.
AB  - OBJECTIVES: To establish the relationship between nasal patency and the nitric
      oxide (NO) concentration in the nasal airways. METHODS: Unilateral nasal NO
      concentration (n = 11) and inhaled nasal NO concentration at oropharynx (n = 9)
      were measured in healthy adult volunteers. Subjects breathed normally through the
      nose with a known resistance (ranged from none to total occlusion) placed in one
      nostril. In a subgroup (n = 7), the unilateral nasal NO concentrations were
      determined with nasal cavity congestion induced by lateral decubitus. RESULTS:
      When the added nasal resistance was less than 6 cm H(2)0 per liter per second,
      the peak NO concentrations in the nose remained below 80 parts per billion (ppb).
      Thereafter, the higher the resistance, the greater the NO concentration. It was
      up to 1109.7 ppb when the front nostril was totally occluded. There was no
      correlation between oropharyngeal NO concentrations and resistance in the front
      of the nose (r = 0.4). There was a significantly negative correlation between
      nasal cavity volumes and nasal NO concentrations (r = -0.8, P <.001).
      CONCLUSIONS: Increases in nasal resistance to levels encountered in the nasal
      cycle and in recumbency augments the NO concentration within the obstructed side
      of the nose. Although that within the nose changes with patency, the NO
      concentration is constant down to the lower airways. The modulation role of the
      upper airways to the inhaled NO concentration remains unclear.

PMID- 11568614
TI  - Cochlear reimplantation: surgical techniques and functional results.
AB  - OBJECTIVES/HYPOTHESIS: The most common indication for cochlear reimplantation is
      device failure. Other, less frequent indications consist of "upgrades" (e.g.,
      single to multichannel), infection, and flap breakdown. Although the percentage
      of failures has decreased over time, an occasional patient requires
      reimplantation because of device malfunction. The varying designs of internal
      receiver/stimulators and electrode arrays mandate an examination of the nature
      and effects of reimplantation for the individual designs. The purpose of the
      current study was to investigate the reimplantation of several implant designs
      and to determine whether differences in surgical technique, anatomical findings,
      and postoperative performance exist. STUDY DESIGN: Retrospective chart review.
      METHODS: The subjects were 33 of 618 severely to profoundly deaf adults and
      children who had implantation at the New York University Medical Center (New
      York, NY) between February 1984 and December 2000. The subjects had previously
      had implantation with either a single-channel 3M/House (House Ear Institute, Los
      Angeles, CA) or 3M/Vienna (Technical University of Vienna, Vienna, Austria)
      device or with one of the multichannel Clarion (Advanced Bionics, Sylmar, CA),
      Ineraid (Smith & Nephew Richards, TN), or Nucleus (including the Contour) devices
      (Cochlear Corp., Englewood, CO) before reimplantation. RESULTS: Length of use
      before reimplantation ranged from 1 month to 13 years and included traumatic and
      atraumatic (electronic) failures, as well as device extrusion or infection.
      Results indicated that postoperative performance was either equal to or better
      than scores before failure. None of the devices explanted caused damage that
      precluded the implantation of the same or an upgraded device. These findings
      support the efficacy and safety of internal implant designs as related to the
      maintenance of a functional cochlea for the purpose of reimplantation.
      CONCLUSIONS: Cochlear reimplantation can be performed safely and without
      decrement to performance. The number of implanted electrodes at reinsertion were
      either the same or greater in all cases.

PMID- 11568615
TI  - Cochlear implantation in healthy and otitis-prone children: a prospective study.
AB  - OBJECTIVE: To evaluate and compare the timing of surgery, intraoperative
      findings, and otitis media-related outcome of cochlear implantation in children
      who are otitis-prone with their counterparts who are not otitis-prone. STUDY
      DESIGN: Prospective. METHODS: Children referred for cochlear implantation were
      assigned to a non-otitis-prone group (group A: normal otoscopy on their first
      visit after referral) or an otitis-prone group (group B: current or a recent
      history of otitis media at referral). Group B patients were managed using a
      structured protocol aimed at preimplantation otitis media control. The study
      reviewed pre-, intra-, and postoperative data. RESULTS: Of the 18 children
      studied, 8 were assigned to group A (mean age at referral, 40.6 mo) and 10 to
      group B (mean age at referral, 31.6 mo). For otitis media control, all otitis
      prone children underwent ventilating tube insertion (various numbers of
      procedures before implantation). Only one otitis-prone child required cortical
      mastoidectomy also. Time from referral to implantation was similar in the two
      groups (mean, 6.6 mo). High-resolution computed tomography data showed mastoid
      pneumatization to be significantly smaller in the otitis-prone group, but the
      facial recess was not smaller in this group. During implantation, 10 children had
      inflamed middle ear mucosa. Seven of these belonged to group B. All of these
      seven children had a round window niche obliterated by the inflamed mucosa, which
      had to be removed for round window membrane identification. After implantation,
      only one child had drainage through the ventilating tube for more than 1 week.
      Two children in group B developed otitis media (1 year postimplantation) that was
      overcome within 1 week. There were no otitis media-related complications.
      CONCLUSIONS: If a structured protocol is used for the control of otitis media
      before cochlear implantation, otitis media should not require a delay in
      implantation. In otitis media-prone children, the round window niche is often
      obscured by inflamed mucosa. Its removal is mandatory for identification of the
      round window membrane. After cochlear implantation, otitis media is not a
      frequent occurrence.

PMID- 11568616
TI  - Otological manifestations of Churg-Strauss syndrome.
AB  - OBJECTIVES/HYPOTHESIS: To describe the clinical features, pathogenesis, and
      management of the otological complications in Churg-Strauss syndrome (CSS). STUDY
      DESIGN: Retrospective review of five patients with documented CSS who had
      otological manifestations in the later stages of CSS. METHODS: The history,
      treatment, and outcome were evaluated using office and hospital chart data in
      these five cases. RESULTS: In all cases, otological manifestations occurred
      during an advanced stage of CSS and was characterized by the presence of dense
      aural discharge, granulomatous eosinophilic infiltration into mastoid and middle
      ear, and subacute severe to profound hearing loss. In all cases, the recurrent
      aural discharge and granulomatous infiltrate was unresponsive to conventional
      treatment including repeated myringotomies and aggressive antibiotics. Systemic
      steroid administration resulted in a rapid, complete cessation of aural discharge
      and reversal or stabilization of hearing loss. Otological manifestations have
      been stable over a range of follow-up from 1 to 20 years on a maintenance regimen
      of steroids. CONCLUSIONS: Temporal bone involvement in CSS is rare. Surgical
      intervention of the temporal bone is relegated to complications that may include
      infectious mastoiditis and intracranial involvement. Recognition of the
      association between CSS and otological disease is important because it is highly
      responsive to systemic steroids, and early steroid treatment may prevent
      progression to irreversible hearing loss, infectious otomastoiditis, or
      intracranial complications.

PMID- 11568617
TI  - Relationship of vestibular aqueduct and inner ear pressure in Meniere's disease
      and the normal population.
AB  - OBJECTIVE: Etiopathogenesis of Meniere's disease has not been resolved. The
      principal histopathologic finding in this disease is endolymphatic hydrops. The
      majority of radiologic and histopathologic studies demonstrated a narrow
      vestibular aqueduct in Meniere's disease. There is no study in the literature
      investigating the relationship between inner ear pressure and vestibular aqueduct
      dimensions. Static acoustic compliance is a noninvasive procedure that is thought
      to measure perilymphatic pressure at the footplate. An increase in mechanical
      fluid pressure in the inner ear is transmitted to the footplate of the stapes.
      This causes a reduction in the compliance at the drum. The aim of this study is
      to investigate the relationship between vestibular aqueduct dimensions and static
      acoustic compliance in Meniere's disease and the normal population. STUDY DESIGN:
      Prospective study. METHODS: Forty patients with Meniere's disease and 40 healthy
      individuals with no otolaryngologic disorders were the subjects of this study.
      Each group was further divided into two according to static compliance value
      (normal and low static compliance). In these four groups dimensions of vestibular
      aqueduct were determined radiologically by high-resolution computerized
      tomography and correlated with normal and low static acoustic compliance values
      (normal and high perilymphatic pressure). RESULTS: The results demonstrated that
      vestibular aqueduct is narrower in patients with Meniere's disease than the
      normal population. However, there is no relationship between vestibular aqueduct
      dimensions and inner ear pressure obtained by static acoustic compliance
      measurements.

PMID- 11568618
TI  - Connection between the inner ear and the lymphatic system.
AB  - OBJECTIVE: The aim of this study was to identify the lymphatic drainage of the
      inner ear in guinea pigs. STUDY DESIGN: Prospective study. METHODS: The
      prospective study was performed in guinea pigs by injection of keyhole limpet
      hemocyanin (KLH) into either the right-side scala tympani or the middle ear
      cavity. The left side was not injected and served as a control. Fifteen minutes
      after injection, the animals were killed by intracardiac perfusion with
      paraformaldehyde and tissue specimens (right and left temporal bones, cervical
      lymph nodes, and the spleen) were collected. The presence of KLH in each specimen
      was determined by immunohistochemical assay of frozen sections using polyclonal
      mouse anti-KLH antibodies. RESULTS: After injection into the middle ear, labeled
      cells were identified in the parotid, superficial ventral, mandibular, and deep
      cranial cervical lymph nodes. However, after inner ear injections KLH was present
      in only the parotid and superficial ventral cervical nodes. The spleen contained
      KLH-positive cells following injection into either the middle or inner ear, but
      not all animals contained labeled spleen cells. CONCLUSIONS: The inner ear has a
      connection to the lymphatic drainage system. Because fewer lymph nodes contained
      labeled cells after inner ear injection than after middle ear injection, it is
      concluded that the inner ear does not simply drain to the middle ear and
      subsequently to the lymph nodes but seems likely to have its own connections.

PMID- 11568619
TI  - Tetracaine topical anesthesia for myringotomy.
AB  - OBJECTIVES/HYPOTHESIS: To study the efficacy and safety of topical tetracaine
      anesthesia for office myringotomy and myringotomy with a tube. STUDY DESIGN:
      Retrospective review of patients undergoing office myringotomy, with or without
      tube insertion, performed over a 4-year period. METHODS: A topical solution of 8%
      tetracaine base in 70% isopropyl alcohol was used in 381 ears. Five to 10 drops
      of the solution were applied to the tympanic membrane for 10 to 15 minutes and
      aspirated. Myringotomy was performed either with a myringotomy knife or with a
      CO(2) laser (OtoLAM). RESULTS: Topical tetracaine was used in all 231 ears (100%)
      undergoing myringotomy without a tube and 150 of 212 ears (71%) undergoing
      myringotomy with a tube. Tetracaine alone was effective in providing tympanic
      membrane anesthesia in 95% of myringotomy without a tube (220 ears) and in 93% of
      myringotomy with a tube (139 ears). There were six complications, including five
      cases of severe vertigo and one unusual prolonged, transient facial nerve
      weakness. CONCLUSION: Topical tetracaine is efficacious and safe for use in
      office myringotomy.

PMID- 11568620
TI  - CO(2) laser treatment in 244 patients with respiratory papillomas.
AB  - OBJECTIVE: Respiratory papillomas (RP) tend to recur and the difficulty in
      eradicating the disease makes their treatment frustrating. Meticulous CO(2) laser
      excisions every 2 months has been the most effective treatment to date. This
      article analyzes the results of this plan in 244 patients with RP in the nose,
      nasopharynx, pharynx, hypopharynx, larynx, trachea, lung parenchyma, and skin.
      METHODS: Two hundred forty-four patients with recurrent RP were treated by the
      senior author with CO(2) laser excisions and, in some cases, podophyllum and
      alpha interferon. Demographics, initial distribution of papillomas, number of
      operations performed on each patient, and current results were evaluated.
      RESULTS: Careful laser excisions of RPs every 2 months achieved "remission" of
      disease (no visible RP on indirect or often direct laryngoscopy 2 mo after last
      removal) in 37% of patients, "clearance" of the disease process (no RP clinically
      apparent for 3 y after last removal) in 6%, and "cure" (no clinical recurrence
      for 5 y after last removal) in 17%. Juvenile-onset RP tends to follow a more
      aggressive course than adult-onset RP. Four patients (1.6%) developed malignant
      transformation of their papillomas. Except for ones in lung parenchyma, RP in
      areas other than the true vocal cords tend to be cleared faster because
      aggressive removal does not cause hoarseness. Lung parenchyma RPs are eventually
      fatal because of pulmonary failure from abscesses and cysts resulting from a lack
      of effective treatment. CONCLUSION: Frequent and meticulously performed CO(2)
      laser excisions can achieve significant voice and airway improvement, and some
      clinical "cures." However, effective antiviral medicines and/or immunologic
      agents are needed to achieve true cures with elimination of all human papilloma
      virus 6 and 11 viruses.

PMID- 11568621
TI  - Acute laryngotracheitis in the rat induced by Sendai virus: the influx of six
      different types of immunocompetent cells into the laryngeal mucosa differs
      strongly between the subglottic and the glottic compartment.
AB  - OBJECTIVES: Acute laryngotracheitis is a disease in which mainly the subglottic
      area is infected, whereas adjacent parts of the larynx, especially the narrow
      glottic fold, remain unaffected. The reason for the difference between these two
      directly adjacent regions is unknown. Therefore, in the present study the influx
      of dendritic cells, neutrophils, T and B lymphocytes, natural killer cells, and
      macrophages into the mucosa of different laryngeal compartments was investigated
      after Sendai virus infection in the rat. The aims were to study both the influx
      of immunocompetent cells and the adhesion of the pathogen and to correlate them
      to the different reactions of the laryngeal areas during pseudocroup. METHODS:
      Acute laryngotracheitis was induced by intranasal application of Sendai virus in
      brown Norway rats. This virus is exclusively pneumotropic in rodents and belongs
      to the parainfluenza virus type 1, the main pathogen of acute laryngotracheitis
      in children. The numbers of dendritic cells, neutrophils, T and B lymphocytes,
      natural killer cells, and macrophages were determined in the supraglottic,
      glottic, subglottic, and tracheal mucosa on days 2, 5, 7, and 14 after virus
      application. Furthermore, the nucleoprotein of the virus and major
      histocompatibility complex (MHC) Class II expression were detected
      immunohistologically on the laryngeal epithelium. RESULTS: All cell subsets
      entered the laryngeal mucosa during inflammation. The highest influx was detected
      among dendritic cells subglottically. This was accompanied by a strong virus
      adhesion and MHC Class II expression on the subglottic epithelium. In contrast,
      only a few immunocompetent cells entered the adjacent glottic mucosa, and on the
      glottic epithelium staining for virus nucleoprotein and MHC Class II expression
      was weak. CONCLUSIONS: The inflammatory response of the laryngeal mucosa shows
      great regional differences in this animal model during experimental viral
      infection. The response was characterized by a strong subglottic and a weak
      glottic reaction. A possible reason for this difference might be region-specific
      viral adhesion on the epithelium of the laryngeal areas, as well as differences
      in MHC Class II expression. Thus, these data agree with the clinical observation
      during acute laryngotracheitis and may explain why the subglottic part of the
      larynx is affected preferentially during pseudocroup. The molecular mechanisms
      mediating the different reactions await clarification.

PMID- 11568622
TI  - Upper airway edema resulting from use of Ecballium elaterium.
AB  - OBJECTIVES: To present a rare occurrence in ear, nose and throat practice of
      upper airway allergic edema from use of juice extracted from the fruit of
      Ecballium elaterium. INTRODUCTION: Ecballium elaterium is a plant indigenous to
      the Mediterranean region that bears the common name squirting cucumber. Many
      people in this region for the treatment of sinusitis use the juice of its fruit.
      However, allergy-prone patients after using it may sometimes present with edema
      at various sites of the upper respiratory tract. Otolaryngologists are frequently
      asked to diagnose and treat such an emergency situation. STUDY DESIGN:
      Retrospective review of the records of 42 patients with this condition during the
      last 4 years. METHODS: Patient records were retrospectively reviewed for age,
      sex, presenting symptoms, physical examination, and medical treatment. Seasonal
      distribution and data from the history of the patients were also considered. Skin
      prick and prick-to-prick testing to various allergens was performed in 12
      patients. RESULTS: Most of the patients presented with localized swelling of the
      uvula and the nasal mucosa, whereas in the remainder of the patients various
      sites of swelling of the upper respiratory tract were observed. Skin tests
      elicited positive reactions to pollen weeds and to various fruits of the
      Cucurbitaceae family. Treatment of the patients with corticosteroids and
      antihistamines resulted in an uneventful recovery, and we did not need to resort
      to therapeutic modalities, such as intubation or tracheotomy. CONCLUSIONS: We
      think a further study of the pharmaceutical properties of the plant's fruit juice
      is needed, especially regarding its curative properties of rhinitis and
      sinusitis. However, adverse reactions in some patients with a positive history of
      allergy should always be considered.

PMID- 11568623
TI  - Detection of macrophage migration inhibitory factor (MIF) in human cholesteatomas
      and functional implications of correlations to recurrence status and to
      expression of matrix metalloproteinases-3/9, retinoic acid receptor-beta, and
      anti-apoptotic galectin-3.
AB  - OBJECTIVES: To investigate whether the expression of the macrophage migration
      inhibitory factor (MIF) 1) is detectable, 2) changes in relation to recurrence
      and infection status, and 3) relates to the levels of expression of growth
      regulators/differentiation markers, including galectin-1, -3, and -8, retinoid
      acid receptors (RAR)]-alpha, -beta, and -gamma, binding sites for sarcolectin,
      and invasion markers (cathepsins -B and -D, and matrix metalloproteinases [MMP]
      2, -3, and -9) in human cholesteatomas. STUDY DESIGN: An analysis of 56
      cholesteatomas resected by the same surgeon using canal wall up and canal wall
      down surgical procedures. METHODS: The immunohistochemical levels of expression
      of MIF and the proteases were quantitatively determined (using computer-assisted
      microscopy) on routine histologic slides by specific antibodies, and
      statistically correlated to parameters of the other markers determined previously
      in conjunction with data on apoptosis/proliferation. RESULTS: MIF expression was
      detected. It was significantly higher in the epithelium (P =.002) and vessels (P
      =.04) of the connective tissues (but not in the connective tissue itself) of
      recurrent as opposed to non-recurrent cholesteatomas. The MIF expression is
      significantly correlated (P =.006) to the RAR beta expression in non-infected
      cholesteatomas, and to MMP-3 (P <.01) and anti-apoptotic galectin-3 (P =.01) in
      infected cholesteatomas. The level of MIF expression was also correlated
      significantly to MMP-9 (P = 0.003), RAR beta (P <.001), and galectin-8 (P =.003)
      expression in the cholesteatomas regardless of their infection status.
      CONCLUSIONS: MIF expression in human cholesteatomas is related to the levels of
      biologic aggressiveness reflected in their recurrence status and MMP expression,
      and to the differentiation status reflected in their galactin and RAR beta
      expressions. Together with galectin-3, it could cooperate to form an anti
      apoptotic feedback loop.

PMID- 11568624
TI  - A failsafe technique for endoscopic tracheoesophageal puncture.

PMID- 11568625
TI  - The use of palatal island flaps as an adjunct to microvascular free tissue
      transfer for reconstruction of complex oromandibular defects.
AB  - OBJECTIVE: To determine the efficacy of using palatal island flaps in combination
      with free tissue transfer for reconstruction of large, complex oral cavity
      defects. STUDY DESIGN: Prospective evaluation of patients with large, combined
      defects of the oral cavity reconstructed with palatal flaps in conjunction with
      microvascular free tissue transfer. METHODS: Elevation of a palatal flap was
      performed after completion of tumor resection. The flap was rotated and secured
      into place. A free flap was then harvested and inset to reconstruct the remaining
      oromandibular defect. Free flaps included the rectus abdominis (6), fibula (16),
      and radial forearm (6). RESULTS: Large complex oral cavity defects were repaired
      with a palatal island flap in conjunction with microvascular free tissue transfer
      in 28 consecutive patients. There were no complications associated with this
      flap. CONCLUSION: Maximal functional rehabilitation of large, complex oral
      defects requires independent reconstruction of the various regions of the oral
      cavity rather than single flap reconstruction. When used as an adjunct to free
      tissue transfer, the palatal island flap offers a reliable method for
      reconstructing large combination defects.

PMID- 11568626
TI  - Eosinophilic mucin rhinosinusitis.

PMID- 11568627
TI  - Endogenous nociceptin signaling and stress-induced analgesia.
AB  - Nociceptin/orphanin FQ (NC) and its receptor (OP4) have been implicated in pain
      transmission. The aim of the present study was to investigate the role of the
      NC/OP4 system in stress-induced analgesia (SIA). The tail-withdrawal assay was
      performed in mice stressed by forced swimming in water at 15 degrees C (high
      severity swims) or 32 degrees C (low severity swims). High severity swims
      produced a naloxone-insensitive antinociceptive effect which was blocked by
      supraspinal NC (1 nmol). The selective OP4 receptor antagonist, [Nphe1]NC(-13)NH2
      (30 nmol), was inactive by itself, but prevented the effect of NC. Low severity
      swims produced a milder analgesic effect that was partially antagonized by
      naloxone, completely blocked by NC and potentiated by [Nphe1]NC(-13)NH2. These
      findings confirm the anti-analgesic role of supraspinal NC and suggest that
      endogenous NC signaling counteracts the opioid component of SIA.

PMID- 11568628
TI  - Event-related brain potentials isolate the motor component in a tapping task.
AB  - Repetitive tapping is used to investigate temporal perception, memory, and
      reproduction. Intertap intervals and their variability, arise from cognitive and
      motor processes during the task. We used a measure of readiness potential onset
      to determine motor component latency during the timed interval. Subjects
      performed a paced, two-handed tapping task at four target intervals (1.5-2.75 s).
      Overall latency of production increased with increasing ISI, as did variability
      across target interval, conforming to a generalized Weber's law. In contrast,
      average motor latency was roughly 0.5 s across ISI. This constant motor latency
      may also indicate constant variability attributable to motor processing.

PMID- 11568629
TI  - Neonatal novelty exposure modulates hippocampal volumetric asymmetry in the rat.
AB  - Early life environmental manipulations have been shown to affect hippocampal
      dependent learning, hippocampal volume and cerebral lateralization. In this
      study, we investigated the effects of neonatal stimulation on hippocampal
      volumetric asymmetry. Long-Evans hooded rats were exposed to a novel non-home
      environment 3 min daily for the first 3 weeks of life. Histological measures of
      the left and right hippocampus were made at 8 months of age. We found that
      neonatal novelty exposure resulted in a long-lasting change in hippocampal
      volumetric asymmetry. Specifically, this brief and transient early life
      stimulation increased the right hippocampal volumetric dominance at mid
      adulthood.

PMID- 11568630
TI  - Intracellular calcium signals in the surround of rat visual cortex lesions.
AB  - Focal lesions of the visual cortex induce deafferentiation, excitotoxic cell
      death as well as functional reorganization in the surrounding tissue. The
      intracellular second messenger calcium is involved in a wide range of cellular
      responses including excitotoxicity and functional reorganization following
      cortical injuries. We investigated the intracellular calcium concentration
      [Ca2+]i in neurons of the visual cortex using fluorescence imaging of fura-2
      signals in a slice preparation obtained from lesioned and sham-operated cortices.
      We observed an increase in resting and stimulus evoked [Ca2+]i in the surround of
      the lesion, which were mediated by NMDA and non-NMDA ionotropic glutamate
      receptors. This increase in [Ca2+]i might be an important factor for lesion
      induced functional reorganization in the rat visual cortex.

PMID- 11568631
TI  - Activation of microglia and astrocytes by CpG oligodeoxynucleotides.
AB  - Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated
      CpG motifs stimulate cells of the immune system to secrete a variety of cytokines
      and chemokines. This function can be carried out by microglia and astrocytes in
      the CNS. To evaluate the effect of CpG ODN on microglia and astrocytes, purified
      cells were isolated and cultured in vitro. CpG ODN rapidly up-regulated their
      production of IL-1beta, IL-6, IL-12, TNFalpha, MIP-1alpha and/or MIP-1beta. In
      vivo, systemically administered CpG ODN up-regulated the expression of mRNA
      encoding cytokines and chemokines in normal mouse brain. These findings suggest
      that CpG ODN can directly activate immune cells of the CNS.

PMID- 11568632
TI  - Light-emitting diode treatment reverses the effect of TTX on cytochrome oxidase
      in neurons.
AB  - Light close to and in the near-infrared range has documented benefits for
      promoting wound healing in human and animals. However, mechanisms of its action
      on cells are poorly understood. We hypothesized that light treatment with a light
      emitting diode array at 670 nm (LED) is therapeutic in stimulating cellular
      events involving increases in cytochrome oxidase activity. LED was administered
      to cultured primary neurons whose voltage-dependent sodium channels were blocked
      by tetrodotoxin. The down-regulation of cytochrome oxidase activity by TTX was
      reverted to control levels by LED. LED alone also up-regulated enzyme activity.
      Thus, the results are consistent with our hypothesis that LED has a stimulating
      effect on cytochrome oxidase in neurons, even when they have been functionally
      silenced by TTX.

PMID- 11568633
TI  - Cytochrome oxidase activity is increased in +/Lc Purkinje cells destined to die.
AB  - +/Lc Purkinje cells degenerate postnatally because of a gain-of-function mutation
      in the delta2 glutamate receptor (Grid2) that causes a constitutive Na+ current
      leak. The effect of the resulting chronic depolarization on Purkinje cell
      metabolism was investigated by measuring levels of cytochrome oxidase (COX)
      activity in Purkinje cell dendrites using quantitative densitometry. Analysis of
      wild type controls and +/Lc mutants at P10, P15 and P25 showed that levels of COX
      activity were significantly increased above control levels by P15 and continued
      to increase through P25. The increase in COX activity is likely to reflect an
      increase in oxidative phosphorylation to accommodate the energy demands of
      removing excess Na+ and Ca2+ entering the Purkinje cells in response to the Grid2
      leak current.

PMID- 11568634
TI  - Human brain mapping of auditory imagery: event-related functional MRI study.
AB  - We used event-related fMRI methodology to investigate human brain activity during
      auditory imagery. A series of susceptibility-weighted MR images covering the
      whole brain were acquired to obtain blood oxygenation level-dependent (BOLD)
      signal changes associated with the imagery event of hearing simple monotone.
      Group analysis across the 12 right-handed subjects revealed activations in the
      medial and inferior frontal gyri, precuneus, middle frontal gyri, superior
      temporal gyri, and anterior cingulate gyri. Bilateral primary and secondary
      auditory areas in the superior temporal gyri also exhibited the event-related MR
      signal changes. The proposed method allowed for the analysis of brain areas
      responsive to the event of auditory imagery while our results suggest that
      auditory imagery and actual audition share common neural substrates.

PMID- 11568635
TI  - Transtympanic tetrodotoxin alters the VOR and Fos labeling in the vestibular
      complex.
AB  - The sodium channel blocker tetrodotoxin (TTX) is an effective tool for blockade
      of action potentials. Unilateral transtympanic administration of 3 mM TTX
      produced behavioral symptoms similar to those following unilateral peripheral
      vestibular ablation. Complete resolution of visible symptoms occurred between 48
      and 72 h post-TTX. Eye-coil recordings indicated a spontaneous nystagmus and a
      decrease in the VOR in TTX-treated animals. Neuronal activity in the central
      vestibular complex (VC), as monitored with Fos immunocytochemistry, revealed an
      asymmetric pattern of Fos labeling in the medial, inferior and superior
      vestibular nuclei and the prepositus hypoglossal nucleus. Although the spatio
      temporal pattern of Fos labeling was consistent and reproducible at each time
      point, changes were noted among time-points. Transient blockade with TTX may be
      useful for studying the central vestibular response to recurrent or episodic
      vestibular disruption in the intact system.

PMID- 11568636
TI  - A1 adenosine receptor activation inhibits neurite process formation by Rho kinase
      mediated pathways.
AB  - A1 adenosine receptors (A1ARs) are expressed in the brain during critical periods
      of neurogenesis and neuronal differentiation. To examine influences of A1AR
      activation on neuronal development we studied the effects of A1AR activation on
      process growth in PC12 cells expressing A1ARs and in primary cultures of cortical
      and hippocampal neurons. In PC12 cells, we found that A1AR activation potently
      inhibited nerve growth factor (NGF)-induced neurite growth and induced stress
      fiber formation. A1ARs action was not mediated by inhibition of p44/42 MAP kinase
      activity, as inhibition of MEK/MAP kinase had no effects on A1AR action. When Rho
      kinase activity was blocked, A1AR agonists no longer inhibited neurite growth and
      stress fiber formation was blocked. In neurons, A1AR activation also inhibited
      process growth, and A1AR action was also mediated by Rho kinase. These data show
      that A1AR activation inhibits neurite growth and that the inhibitory effects of
      A1AR are dependent on Rho kinase.

PMID- 11568637
TI  - Sex-induced fos in the medial preoptic area: projections to the midbrain.
AB  - Sexual activity results in cells displaying Fos-like Immunoreactivity (FLI) in
      the medial preoptic area (MPOA) of male rats. This study combined retrograde
      tracing techniques with FLI to determine if MPOA cells displaying sex-induced FLI
      project to known efferent sites of the MPOA. FluoroGold was injected into the
      dorsal central gray, lateral central gray, ventral tegmental area, medial central
      tegmental field, or lateral central tegmental field of male rats that later
      engaged in sexual activity. Examination of FLI and FluoroGold in the MPOA
      revealed that the lateral region of the MPOA projected to the lateral central
      gray and contained smaller projections to the other regions. These findings
      suggest that the lateral MPOA contains secondary sex-relevant projections to the
      midbrain.

PMID- 11568638
TI  - Differential in vivo internalization of MOR-1 and MOR-1C by morphine.
AB  - The mu opioid receptor MOR-1 is internalized by many mu agonists, but not
      morphine. To see whether differences in the intracellular carboxy terminus
      influences internalization, we examined internalization of a splice variant of
      the mu opioid receptor, MOR-1C, in the lateral septum of the mouse in vivo.
      Following intracerebroventricular (i.c.v.) saline treatment, MOR-1C-like
      immunoreactivity (LI) within neurons in naive mice was found predominantly in
      clusters close to the plasma membrane. Following either intracerebroventricular
      [d-Ala2, MePhe4,Gly(ol)5]enkephalin (DAMGO) or morphine, MOR-1C-LI clustered into
      endosomes in the cytoplasm. This effect was suppressed by prior administration of
      the opioid antagonist naloxone. In contrast, only DAMGO, and not morphine,
      internalized MOR-1-LI. These results illustrate differences in internalization
      between two MOR-1 variants that have alternative splicing at the COOH terminus.

PMID- 11568639
TI  - Adenovirus-mediated GDNF protects cultured motoneurons from glutamate injury.
AB  - The protective effects of adenovirus-mediated glia cell line-derived neurotrophic
      factor (GDNF) gene transaction was investigated on cultured motoneurons. First,
      the dose- and time-response relationship of glutamate neurotoxicity was
      determined on spinal motoneuron cultures. Then, the effect of the gdnf
      recombinant adenovirus (AdCMVgdnf) was tested in this cellular model. AdCMVgdnf
      at 20 MOI (multiplicity of infection) was found to significantly reduce the cell
      loss of motoneurons, as compared to AdCMVgdnf at 20 MOI, the recombinant
      adenovirus containing the marker gene lacZ. Furthermore, the adenovirus was
      proved to mediate erogenous gene expression using X-Gal staining and a semi
      quantitative RT-PCR method. These results suggested a therapeutic potential of
      adenovirus vector-mediated gdnf gene therapy in human motoneuron diseases.

PMID- 11568640
TI  - A role for the TTX-resistant sodium channel Nav 1.8 in NGF-induced hyperalgesia,
      but not neuropathic pain.
AB  - The tetrodotoxin-resistant voltage-gated sodium channel Nav 1.8 is expressed only
      in nociceptive sensory neurons. This channel has been proposed to contribute
      significantly to the sensitization of primary sensory neurons after injury. We
      have studied the nociceptive behaviours of mice carrying a null mutation in the
      Nav 1.8 gene (Nav 1.8 -/-) in models of peripheral inflammation as well as a
      model of neuropathic pain. The results from the present studies reveal that Nav
      1.8 is a necessary mediator of NGF-induced thermal hyperalgesia but is not
      essential for PGE2-evoked hypersensitivity. Neuropathic pain behaviours were
      unchanged in Nav 1.8 -/- mice indicating that this channel is not involved in the
      alteration of sensory thresholds following peripheral nerve injury.

PMID- 11568641
TI  - Hyperanxiety produced by periaqueductal gray injection of chondroitin sulphate
      glycosaminoglycan.
AB  - We examined the effects of chondroitin sulphate C (CSC) on fear and anxiety
      parameters following injection of the glycosaminoglycan into the dorsal
      periaqueductal gray. Rats with chronically implanted cannulae were administered
      CSC (0.4 or 4.0 nmol) or vehicle (saline, 0.2 microl) and exposed to the elevated
      plus-maze test of emotionality. Intra-periaqueductal gray injection of CSC
      produced a dose-dependent anxiogenic effect as indicated by reduced entries into
      and time spent on the open arms, fewer excursions into the end of the open arms
      and by increased stretched attend posture, flat back approach and closed arm
      peeping-out behaviour. The behavioural effects of CSC appeared to be
      anxioselective, since the glycosaminoglycan did not influence measures of general
      (exploratory) activity, such as number of entries into the enclosed arms and
      amount of scanning, rearing and grooming. The present results show that CSC can
      produce an anxiogenic-like profile after injection into the dorsal periaqueductal
      gray. This is the first such report implicating an endogenous matrix
      glycosaminoglycan in neural mechanisms governing fear and anxiety.

PMID- 11568642
TI  - Similar genetic mechanisms may underlie sleep-wake states in neonatal and adult
      rats.
AB  - Genetic differences in the characteristics of sleep-wake states in adult animals
      offer a potential window for examining how the neonatal and adult behavioural
      states are related to one another. Our recent finding that adult Wistar-Kyoto
      (WKY) rats show pronounced genetic differences in sleep-wake patterns relative to
      the Wistar (WIS) control strain led us to investigate the relationship between
      these behavioural states in neonates and adults in a longitudinal study in these
      two strains of rats. Similar pronounced differences in the sleep-wake states were
      observed between WKY and WIS rats in neonatal and in adult animals. At both ages,
      WKY rats spent more time in activesleep (AS) and rapid eye movement sleep (REMS)
      and less time in quiet sleep (QS) and non-REM sleep (NREMS) than WIS rats, and
      the sleep-wake states were more fragmented in neonatal and adult WKY rats. While
      it is not known how neonatal AS and QS are physiologically related to adult REMS
      and NREMS, respectively, the finding of similar differences in the amounts of
      sleep-wake states in neonatal and adult WKY and WIS rats argues strongly that at
      some level they are controlled by similar genetic as well as
      cellular/physiological mechanisms.

PMID- 11568643
TI  - Balance control and posture in anxious mice improved by SSRI treatment.
AB  - A task requiring dynamic postural stabilisation during locomotion in a
      conflicting visual vestibular environment (rotating beam), has been devised to
      assess anxiety-related balance impairments and postural changes in mice. The
      model, already validated with acutely administered diazepam, was used to assess
      the action of two chronically administered selective serotonin reuptake
      inhibitors (SSRIs), fluoxetine and paroxetine. On three behavioural measures
      (imbalance, elevation of trunk and angle of tail), observed in anxious BALB/cByJ
      mice, both compounds had the same diazepam-like effects: reduction in number of
      imbalances, higher elevation of trunk and increase in tail angle. These data
      suggest, for the first time, that SSRIs should be useful in the treatment of
      anxiety-induced balance impairments.

PMID- 11568644
TI  - Locus coeruleus noradrenergic lesions attenuate intraoral intake.
AB  - I.p. injections of DSP-4 in male rats decreased norepinephrine (NE) levels to
      varying degrees throughout the brain with 66.7% reductions in the hypothalamic
      paraventricular nucleus. Intake of intraorally infused sucrose was reduced for 14
      days but daily pellet intake recovered within 5 days post-injection.
      Intraventricular NE restored intraoral sucrose intake in DSP-4-lesioned rats
      without affecting controls. Intraventricular infusion of neuropeptide Y (NPY)
      reduced intraoral intake in controls but had no effect in DSP-4-lesioned rats.
      NPY markedly inhibited intraoral intake in DSP-4-treated rats that also received
      NE. These data confirm studies showing that NPY decreases consummatory ingestive
      behavior and suggest that this inhibition involves ascending noradrenergic
      projections from locus coeruleus.

PMID- 11568645
TI  - Jejunal or portal vein infusions of lipids increase hepatic vagal afferent
      activity.
AB  - Jejunal infusions of linoleic acid, corn oil, or caprylic acid significantly
      increased hepatic vagal afferent activity, whereas saline infusions were
      ineffective. The magnitude of response was greatest with either linoleic acid or
      corn oil. Hepatic portal infusions of linoleic acid, Liposyn II, or caprylic acid
      significantly increased hepatic vagal afferent activity, whereas 5%
      albumin/phosphate buffer vehicle was ineffective. The magnitude of response was
      greatest with either linoleic acid or Liposyn II. These data show that either
      jejunal or portal infusions of lipids increase activity of hepatic vagal
      afferents and could potentially serve as a complementary and/or alternative
      substrate to celiac vagal afferents in mediating the effects of jejunal infusions
      of lipids in suppressing food intake.

PMID- 11568646
TI  - Galectine-1 expression in cochleae of C57BL/6 mice during aging.
AB  - Presbycusis is a progressive hearing loss related to the aging process associated
      with auditory receptor degeneration. Adult animals exhibited galectine-1 (GAL-1)
      expression in epithelial cells of the inner and outer spiral sulci and Hensen
      cells, which was absent from the sensory and supporting cells. The progressive
      age-related degeneration of auditory receptor was analyzed using an anti-GAL-1
      monoclonal antibody on cochleae of C57BL/6 mice (1-24 months old). Mice < or = 9
      months old showed adult and healthy auditory receptors, with a similar GAL-1
      expression along the time. Conversely, animals > 1 year old exhibited a sensory
      degeneration at the cochleae basal coil that progressively reached the middle
      coil. Older animals (18-24 months old) showed a single layer epithelium that
      replaced the auditory receptor. The age-related degenerative process of the
      auditory receptor involves sensory but also supporting cells, which are both
      substituted by epithelial non-specialized cells.

PMID- 11568647
TI  - Dietary fat up-regulates the apolipoprotein E mRNA level in the Zucker lean rat
      brain.
AB  - High-fat diet alters apo E-dependent processing of beta-amyloid precursor
      protein. Here we have evaluated the effects of dietary fat on brain apo E mRNA in
      Zucker lean and obese rats. After approximately 2 months on a high-fat diet,
      there was significant up-regulation of brain apo E mRNA in the Zucker lean rat in
      parallel with weight gain. Densitometric quantification revealed a 17% increase
      in apo E mRNA in the brains of lean rats fed high-fat diet compared with those of
      lean rats fed rat chow. No significant difference in brain apo E mRNA of Zucker
      obese rats fed different diets was found. These results suggest that dietary fat
      alters brain apo E levels, which may be regulated, in part, through the leptin
      receptor.

PMID- 11568648
TI  - Hyperpolarisation-activated current in glomerular cells of the rat olfactory
      bulb.
AB  - Whole-cell patch-clamp recordings were carried out in visually identified
      periglomerular and external tufted cells of rat olfactory bulb. Most of the
      neurones showed a slowly developing hyperpolarisation-activated current with a
      threshold generally positive to resting potential and with a strongly voltage
      dependent activation time constant. The current, identified as Ih, was sodium-
      and potassium-sensitive, suppressed by external caesium, and insensitive to
      barium. Under current-clamp conditions, perfusion with caesium induced a 10 mV
      hyperpolarisation and a marked reduction of the rate of low-frequency
      oscillations induced experimentally. It is concluded that most of the cells in
      the rat glomerular layer present a distinct h-current, which is tonically active
      at rest and which may contribute to the oscillatory behaviour of the bulbar
      network.

PMID- 11568649
TI  - Lead inhibition of NMDA channels in native and recombinant receptors.
AB  - NMDA channels are key targets for lead (Pb2+) neurotoxicity and Pb2+-induced
      inhibition of NMDA current is age- and subunit-dependent. In rat cerebellar
      granule cells maintained in high KCl, glycine affinity as well as sensitivity to
      ifenprodil change significantly with the days in vitro, indicating a reduction of
      NR2B subunit expression. Pb2+ blocked NMDA current with IC50 approximately 4
      microM and this effect decreased significantly during the second week in vitro.
      In Xenopus laevis oocytes expressing recombinant NR1-NR2A, NR1-NR2B or NR1-NR2C
      receptors, Pb2+ inhibited glutamate-activated currents with IC50 of 3.3, 2.5 and
      4.7 microM respectively. These data indicate that Pb2+ action is dependent on
      subunit composition and suggest that down-regulation of the NR2B subunit is
      correlated to a diminished sensitivity to Pb2+ inhibition.

PMID- 11568650
TI  - Region-specific expression of cell cycle inhibitors in the adult brain.
AB  - In the adult brain, neural proliferation is almost absent and neurons are
      generally not renewed. By contrast, in the olfactory organ, olfactory neurons are
      produced continuously throughout life. To investigate whether specific cell cycle
      inhibitors are involved in the control of neural quiescence in adulthood, we
      compared their expression either in different regions of the adult brain weakly
      or non neurogenic or, for comparison, in the olfactory mucosa. We show that
      numerous cell cycle inhibitors are expressed in the adult brain either in an
      ubiquitous fashion (as p19Ink4d) or in specific brain regions (p15Ink4b in the
      forebrain, p27Kip1 and p21Cip1 in the cerebellum). By contrast p18Ink4c was
      expressed detectably only in the highly neurogenic olfactory epithelium. The
      present data suggest that various CDK inhibitors may be involved in a region
      specific fashion in the maintenance of nerve cell quiescence in adults.

PMID- 11568651
TI  - Selective spatial attention induces short-term plasticity in human somatosensory
      cortex.
AB  - Early cognitive process in the primary somatosensory cortex (SI) was studied by
      measuring somatosensory evoked magnetic fields during selective attention tasks.
      We used vibratory stimuli to the index or middle finger with a frequency of 100
      or 400 Hz for selective discrimination of spatial finger and non-spatial
      frequency attribute of stimuli. An early M50 component from the SI cortex
      indicated that the SI regions for the fingers were specifically segregated in a
      finger discrimination task but not in a frequency discrimination task or in a
      control condition. The task-dependent and immediate switchover of cortical finger
      representation demonstrates a dynamic SI activation for spatial information
      processing.

PMID- 11568652
TI  - How changes in vestibular and visual reference frames combine to modify body
      orientation in space.
AB  - The aim of this study was to analyse how changes in vestibular and visual
      reference frames combine to modify body orientation in space, and to determine
      the relationship between postural, oculomotor and perceptive parameters. Changes
      in vestibular and visual references were investigated by comparing controls and
      vestibular defective patients (Meniere's patients tested before and one week
      after unilateral vestibular nerve section) under three visual contexts (light
      with and without vertical and horizontal coordinates, darkness). Unilateral
      vestibular loss was responsible for postural and perceptive deviations whose
      direction depended on the presence of visual reference frame. We suggest these
      changes vary according to the spatial reference frame patients are based on.
      Postural changes were related to perceptive modifications but not to eye
      cyclotorsion.

PMID- 11568653
TI  - Interleukin-6 expression in exo-focal neurons after striatal cerebral ischemia.
AB  - Although anatomical and biochemical properties of the rat entopeduncular nucleus
      (EPN) closely resemble those of the substantia nigra pars reticulata (SNr), the
      present study shows that, unlike in the SNr, focal cerebral ischemia does not
      cause trans-synaptic degeneration of EPN neurons, despite striatal infarction and
      a similar delayed glial activation in both nuclei. In this study, interleukin-6
      (IL-6) expression was found within EPN neurons 3 and 7 days after striatal
      ischemia. Since it has been reported that neuroprotective properties seem to
      predominate IL-6 function and that distinct SNr regions which demonstrate low
      trans-synaptic neuronal degeneration show high IL-6 expression and vice versa, IL
      6 expression within partially deafferentiated but surviving EPN neurons could
      represent an intrinsic neuroprotective mechanism.

PMID- 11568655
TI  - Electrophysiological evidence for automatic phonetic processing in neonates.
AB  - At least two fundamental properties should be present in a network computing a
      phonetic representation: categorical perception and normalization across
      different utterances. Normalization processes were studied at birth by recording
      high density evoked potentials to strings of syllables in sleeping neonates. We
      compared the response to a change of phoneme when irrelevant speaker variation
      was present or absent. A mismatch response was recorded at the same latency in
      both cases, suggesting that relevant phonetic information was extracted from the
      irrelevant variation. Combined with our previous work showing that the mismatch
      response is sensitive to categorical perception in infants, this result suggests
      that a phonetic network like that of adults, is already present in the infant
      brain. Furthermore, efficient phonetic processing does not require attention.

PMID- 11568654
TI  - Two- and three-stimuli auditory oddball ERP tasks and neuropsychological measures
      in aging.
AB  - The purpose of this study was to decide whether the P300 from an auditory three
      stimuli oddball task is more sensitive to aging than the P300 from a two-stimuli
      task, and to investigate the relationship between neuropsychological tests and
      the different ways of eliciting the P300. Thirty-one adults (21.8-94.7 years)
      completed five neuropsychological tests and two ERP tasks. The way P300 was
      elicited did not influence its relationship to aging or neuropsychological
      scores, and the correlations between the two paradigms were strong for amplitude,
      but rather weak for latency. The main conclusion is that the P300 from an
      auditory three-stimulus paradigm is sensitive to aging and neuropsychologically
      valid.

PMID- 11568656
TI  - Nociceptin-induced internalization of the ORL1 receptor in human neuroblastoma
      cells.
AB  - Nociceptin/orphanin FQ (NC) has been proposed as endogenous ligand of the opioid
      receptor-like 1 (ORL1) receptor. We investigated NC-induced internalization and
      recycling of the ORL1 receptor in SK-N-BE human neuroblastoma cells.
      Internalization was proven by receptor binding assay on viable cells. NC promotes
      a time- and concentration-dependent internalization of the ORL1 receptor (57% of
      cell surface receptors are lost after 30 min exposure to 1 microM NC) in a
      clathrin- and ATP- dependent manner. After 30 min exposure to NC, ORL1 receptor
      internalization is partially reversible and recycling is dependent on acid
      phosphatases. Over-expression of beta-arrestin 2 increases NC-promoted
      internalization of the ORL1 receptor. These events contribute to NC signaling in
      neuronal cells through sequestration and recycling of the ORL1 receptor.

PMID- 11568657
TI  - No evidence for bradykinin B1 receptors in rat dorsal root ganglion neurons.
AB  - Bradykinin receptors are believed to contribute to hyperalgesia under conditions
      of neuropathic pain. Using calcium imaging we investigated responses to B1 and B2
      agonists on isolated rat dorsal root ganglion neurons. No response to the B1
      agonist was detected, whereas 12% of neurons responded to the B2 agonist.
      Northern blot analysis confirmed the lack of B1 receptor expression in dorsal
      root ganglia, as B1 mRNA was neither detected under normal conditions nor after
      nerve injury. In the calcium imaging experiments, agonists were applied with an
      elevated superfusion flow rate to avoid tachyphylaxis to the drug. Normal
      external solution applied at this flow rate constituted a mechanical stimulus
      causing a response in some neurons. Thus, in comparable set-ups
      mechanosensitivity has first to be tested to avoid masking effects.

PMID- 11568658
TI  - Pheromone detection in rodents.

PMID- 11568660
TI  - Cholesteatoma prevention by local treatment with vitamin A.
AB  - HYPOTHESIS: In view of the proven effectiveness of vitamin A for the treatment of
      hyperkeratosis, it was hypothesized that vitamin A may also be a feasible
      therapeutic option for cholesteatoma, which has similar histologic features.
      BACKGROUND: Cholesteatoma is a major cause of chronic ear disease, often
      requiring surgery. The recurrence rate may exceed 20%. Hyperkeratosis is a major
      sequela of tympanomastoid surgery, causing chronic ear hygiene problems. METHODS:
      The external auditory canals of 40 Mongolian gerbils were ligated to induce
      cholesteatomas. The ears were divided into three groups by type of treatment:
      group I, vitamin A drops (n = 40); group II, Cortisporin drops (n = 20); group
      III, no treatment (control subjects) (n = 20). Examination for the development
      and grade of cholesteatomas was performed after 9 months. RESULTS: Cholesteatomas
      developed in 26 ears (65%) of group I, 12 ears (60%) of group II, and 20 ears
      (100%) of group III. The differences were significant between groups I and III
      and groups II and III for both rate of cholesteatomas and severity of grade.
      There were no significant differences between groups I and II. CONCLUSION: Local
      treatment reduces the risk of cholesteatomas in ligated gerbilline ears.
      Cortisporin and vitamin A are equally effective as local treatments.

PMID- 11568661
TI  - Localization of matrix metalloproteinase 1 in cholesteatoma and deep meatal skin.
AB  - HYPOTHESIS: Matrix metalloproteinase 1 (MMP-1) is overexpressed in cholesteatoma.
      BACKGROUND: Cholesteatoma destroys bone, whereas deep meatal skin does not. MMP-1
      is a type I collagenase that may be responsible for this destruction. This
      prospective study was designed to identify overexpression of MMP-1 by
      cholesteatoma in comparison with deep meatal skin. METHODS: Ten cholesteatoma
      specimens and nine deep meatal skin specimens were removed during otologic
      surgery and then fixed in formalin and embedded in paraffin. Immunocytochemistry
      studies were performed using a monoclonal antibody to MMP-1. A pathologist
      assessed the slides in a blinded fashion. Expression of MMP-1 protein in
      epidermis and in stroma was scored from 0 to 10. Five further cholesteatoma
      specimens and three deep meatal skin specimens underwent reverse transcriptase
      polymerase chain reactions to assess messenger ribonucleic acid production.
      Paired and unpaired Student's t tests were used to assess the difference in
      expression levels. RESULTS: Cholesteatoma stroma expressed significantly more MMP
      1 protein than did deep meatal skin stroma (p = 0.04). MMP-1 was localized to
      stromal fibroblasts. There was no difference in the epidermal expression levels
      of the two tissue types (p = 0.42). The reverse transcriptase polymerase chain
      reaction showed expression at the messenger ribonucleic acid size of MMP-1 (262
      base pair) in all cholesteatoma specimens examined. One deep meatal skin specimen
      showed a weak signal; no signal was seen in the other specimens. CONCLUSIONS: MMP
      1 is overexpressed by the stromal fibroblasts present in cholesteatoma as
      compared with deep meatal skin. It is possible that these cells rather than the
      keratinocytes are responsible for bone destruction in this disease.

PMID- 11568662
TI  - Open Tubingen titanium prostheses for ossiculoplasty: a prospective clinical
      trial.
AB  - OBJECTIVE: The overall purpose of the study was the evaluation of the efficacy of
      Tubingen titanium prostheses (TTPs) for ossiculoplasty. STUDY DESIGN: A two-part
      clinical study of 216 patients undergoing ossiculoplasty was performed. The first
      part was a prospective study using TTPs (n = 114). The second part involved study
      of historical control patients (n = 102) with gold and ceramic prostheses.
      INTERVENTIONS: All patients underwent ossiculoplasty. MAIN OUTCOME MEASURES:
      Measures included median air conduction thresholds and air-bone gaps. RESULTS:
      All patients were per-protocol patients. When the air-bone gap "gold standard"
      (i.e., < or =10 dB) was investigated in the main speech spectrum, partial TTPs
      reached this level at 2 kHz in 44% (n = 22) and at 3 kHz in 38% (n = 19). Gold
      and ceramics revealed significantly lower values. Similar results were obtained
      for total prostheses. Differences for TTPs and ceramics were statistically
      significant (Mann-Whitney U test, alpha = 5%). CONCLUSION: The use of TTPs for
      ossiculoplasty is an efficient treatment method.

PMID- 11568663
TI  - Analysis of the dysfunctional eustachian tube by video endoscopy.
AB  - OBJECTIVE: Human eustachian tubes with known pathologic conditions of the ear
      were inspected endoscopically, and video recordings were made for slow-motion
      analysis of the pathophysiologic changes. SETTING: Ambulatory office in a
      tertiary referral center. SUBJECTS: Forty-four adults with 64 ears having
      pathologic conditions. INTERVENTIONS: Transnasal endoscopic examination of the
      nasopharyngeal opening of the eustachian tube during rest, swallowing, and
      yawning to study the dilatory movements of the eustachian tube. MAIN OUTCOME
      MEASURES: Slow-motion video analysis of the dilatory movements of the eustachian
      tube. RESULTS: Sixty-four ears and eustachian tubes with pathologic changes were
      studied. Tubal function was graded on (1) the extent of lateral excursion and
      progression of dilatory wave as estimates of tensor veli palatini and dilator
      tube muscle function, reduced function being observed in 43 tubes; (2) the degree
      of mucosal disease, which was significant in 48 tubes; (3) obstructive mucosal
      changes, which were present in 15 tubes; (4) ease and frequency of tubal dilation
      with maneuvers-26 tubes opened moderately, 21 opened minimally, and 11 were
      unable to open; and (5) patulous tubes-all 6 clinically patulous tubes showed
      concavities in the superior third of the tube, which is convex in normal
      subjects. All tubes with active pathologic conditions of the ear (otitis media
      with effusion, tympanic membrane retraction, draining ear, cholesteatoma) had
      significant abnormalities. A correlation could not be made between the severity
      of middle ear disease and the severity of observed eustachian tube dysfunction.
      CONCLUSIONS: Slow-motion endoscopic video analysis is a potentially useful
      technique in classifying types of pathologic changes in the eustachian tube.
      Additional studies of dysfunctional tubes are needed to predict outcomes in
      operative ear cases and to design intratubal therapy for chronically
      dysfunctional tubes.

PMID- 11568664
TI  - Prevalence of otosclerosis in an unselected series of temporal bones.
AB  - BACKGROUND: Histologic otosclerosis is a disease process without clinical
      symptoms or manifestations that can be discovered only by sectioning of the
      temporal bone at autopsy. Clinical otosclerosis is otosclerosis at a site where
      it causes conductive hearing loss by interfering with the motion of the stapes or
      of the round window membrane. Various authors have studied the prevalence of
      histologic otosclerosis on laboratory collections of temporal bones. Some 12% to
      15% of temporal bones with histologic otosclerosis have demonstrated stapedial
      fixation. Using these figures for calculating the prevalence of clinical
      otosclerosis gives an extrapolated clinical prevalence of 0.99% to 1.2%. This
      does not correlate well with the clinical data on otosclerotic families, from
      which a clinical prevalence of 0.3% has been estimated. OBJECTIVE: To study the
      prevalence of histologic otosclerosis in an unselected series of temporal bones.
      STUDY DESIGN: During a 1-year period, 118 consecutive pairs of temporal bones of
      deceased patients at a tertiary care center were collected to determine the
      prevalence of otosclerosis. Although histology remains the gold standard for
      evaluation of otosclerosis, the gross observation of temporal bone slices
      combined with microradiography was used to screen for otosclerotic lesions more
      rapidly and with a lower cost/benefit ratio. The temporal bones, which were
      suspected of having otosclerosis with these techniques, were further analyzed by
      conventional histology. RESULTS: 2.5% of the 236 temporal bones (or 3.4% of
      patients) studied demonstrated histologic otosclerosis. CONCLUSIONS: Although the
      prevalence of 2.5% is much lower than previously published figures on histologic
      otosclerosis, the extrapolated data (extrapolated clinical prevalence = 0.30% to
      0.38%) correlate well with clinical studies of otosclerotic families. The
      previous studies based on laboratory collections were likely biased by hearing
      loss or other otologic diseases.

PMID- 11568665
TI  - The other ear: findings and results in 1,800 bilateral stapedectomies.
AB  - OBJECTIVES: To determine the incidence of middle ear abnormalities in patients
      with bilateral otosclerosis, which could potentially affect successful
      stapedectomy, and the rates of success in these patients, including the chance of
      overclosure in the second ear. STUDY DESIGN: Retrospective case review of
      operative and audiologic records. SETTING: Private otology practice. PATIENTS:
      One thousand eight hundred patients underwent 3,600 primary stapedectomies for
      bilateral otosclerosis. INTERVENTION: Analysis of perioperative and follow-up
      audiograms with associated operative findings, including obliterative
      otosclerosis and solid footplates, dehiscent or overhanging facial nerve, narrow
      oval window niche, promontory overhang, and ossicular fixation or malformation.
      MAIN OUTCOME MEASURES: Audiologic stapedectomy success was determined as
      overclosure or closure of preoperative air-bone gap to less than 10 dB at 1 year
      or more of follow-up. RESULTS: The rate of finding any abnormality was 25%.
      Abnormalities present bilaterally were found in 135 patients (7%), with
      otosclerosis requiring an oval window drillout as the most common finding (41%),
      followed by dehiscent or overhanging facial nerves (25%). Success in patients
      with abnormalities was 78% overall, with bilateral overclosure in 40%.
      CONCLUSIONS: Abnormal middle ear findings during stapedectomy occur in a
      significant percentage of patients. Reasonable rates of success and overclosure
      can still be expected, but this is somewhat finding-specific. The predictive
      value of these findings, the associated rates of success with potential impact on
      surgical counseling, and planning for the "other ear" are discussed.

PMID- 11568666
TI  - Comparative electron microscopic study of the surface structure of gold, Teflon,
      and titanium stapes prostheses.
AB  - HYPOTHESIS: The goal of this study was to compare stapes prostheses of different
      materials with respect to their surface structures and to discuss their
      suitability for their use in stapes surgery. BACKGROUND: The surface condition of
      a stapes prosthesis plays an important role in relation to the type of membrane
      that forms between the stapes piston and the bony edge of the stapedotomy
      opening. The quality of this membrane in thickness and mobility is one of the
      determinants for postoperative hearing improvement. METHODS: The surface
      conditions of gold, Teflon/steel, Teflon/platinum, and titanium stapes prostheses
      were examined with a scanning electron microscope. The loop, shaft, and end of
      each prosthesis were studied. RESULTS: The gold piston was the smoothest of the
      four pistons examined. When it was cut with a scalpel, a very smooth surface was
      achieved at the end area. The Teflon piston had the roughest surface. However,
      when it was cut, a smooth surface with a parallel arrangement of fibers resulted.
      Its steel loop was the smoothest, followed by gold and platinum. The titanium
      shaft had a scaly surface, which remained when the end of the shaft was
      shortened. CONCLUSION: Because a certain roughness of the piston surface is
      necessary for the development of a stable membrane between the piston and the
      edge of the stapedotomy opening, the titanium prosthesis is considered to be the
      most suitable for stapes surgery of the three pistons examined.

PMID- 11568667
TI  - COCH5B2 is a target antigen of anti-inner ear antibodies in autoimmune inner ear
      diseases.
AB  - OBJECTIVE: This study was designed to identify the 58-kDa inner ear protein
      against which the sera of some patients with idiopathic, progressive
      sensorineural hearing loss or Meniere's disease strongly react. BACKGROUND: We
      and other groups have previously demonstrated that a 58-kDa protein extracted
      from guinea pig or bovine inner ear tissue is a target of antibodies in serum
      samples from some patients with autoimmune inner ear diseases. METHODS: After
      separation of inner ear proteins by 10% sodium dodecyl sulfate polyacrylamide gel
      electrophoresis, the bands corresponding to 58 kDa were localized and excised
      from the gel. The concentrated protein was then digested with trypsin, and the
      peptide fragments were separated by high-pressure liquid chromatography. Three
      fractions were subjected to amino acid sequencing by the classic Edman
      degradation. RESULTS: The sequence of a stretch of 14 amino acids of the first
      fragment was identical to that of amino acids 526 to 539 of the COCH5B2 protein.
      The sequences of 11 and 10 amino acids of the second and third fragments,
      respectively, also were identical to residues 417 to 427 and 396 to 405 of the
      COCH5B2 protein. These data, together with two-dimensional gel electrophoresis
      followed by Western blot experiments, confirmed that the 58-kDa inner ear protein
      is the COCH5B2 protein. DISCUSSION: These findings indicate that the 58-kDa
      target protein of antibodies in serum samples of patients with autoimmune inner
      ear diseases is the COCH5B2 protein, a molecule that is highly and specifically
      expressed in the cochlea and vestibule.

PMID- 11568668
TI  - Etanercept therapy for immune-mediated cochleovestibular disorders: preliminary
      results in a pilot study.
AB  - OBJECTIVE: Immune-mediated cochleovestibular disorders (IMCVDs) continue to
      present a management challenge to the otolaryngologist. Antirheumatic agents,
      commonly used for IMCVDs, are associated with variable efficacy and sometimes
      with serious side effects. The authors describe the preliminary result of their
      experience in patients with IMCVDs who have been treated with etanercept, a tumor
      necrosis factor alpha receptor blocker, recently approved by the United States
      Food and Drug Administration for the treatment of rheumatoid arthritis. STUDY
      DESIGN: Retrospective case series. SETTING: Tertiary care hospital. PATIENTS:
      Twelve patients suspected of having IMCVD who did not respond to conventional
      therapies or experienced side effects of the conventional therapies.
      INTERVENTION: Etanercept 25 mg by subcutaneous injection twice per week. MAIN
      OUTCOME MEASURES: The main outcome measurement was assessment of hearing change
      by air conduction pure tone audiograms and/or word discrimination. When present,
      vertigo, tinnitus, and aural fullness were assessed as well. RESULTS: Follow-up
      of more than 5 months was available for all patients (range, 5-12 months). Eleven
      (92%) of 12 patients had improvement or stabilization of hearing and tinnitus,
      seven (88%) of eight patients who had vertigo and eight (89%) of nine patients
      who had aural fullness had resolution or significant improvement of their
      symptoms. The benefit persisted until the last visit (5-12 months after
      etanercept was begun). The condition of one patient improved dramatically at
      first but deteriorated after 5 months. The patient's hearing was rescued and
      stabilized with the addition of leflunomide to etanercept. Similarly, three other
      patients required a second antirheumatic agent to stabilize their hearing. There
      were no significant side effects from the etanercept therapy. CONCLUSIONS: Our
      limited data suggest that etanercept therapy is safe and may be efficacious in
      carefully selected patients with IMCVDs, at least on a short-term basis. These
      preliminary efficacy and safety results appear encouraging enough to warrant
      further follow-up and studies for better determination of the potential clinical
      utility of etanercept for IMCVDs.

PMID- 11568669
TI  - Speech recognition in background noise: monaural versus binaural listening
      conditions in normal-hearing patients.
AB  - HYPOTHESIS: Patients with unilateral conductive hearing impairment often
      experience a great advantage in improved hearing thresholds after reconstructive
      ear surgery because the binaural hearing leads to increased speech recognition in
      competing noise. The aim of this study was to develop a clinical audiometric test
      to quantify the ability of speech recognition in background noise preoperatively
      and postoperatively. METHODS: A model consisting of phonetically balanced (PB)
      monosyllabic words and/or a just-follow-conversation test (JFC) was used in 16
      normal-hearing listeners. In 8 of the participants, JFC at two levels of
      background noise (60 and 40 dB sound pressure level) was used as the only method.
      The tasks were performed in an anechoic chamber with varying spatial separations
      of speech and noise sources under free field conditions. The tests were made
      binaurally and monaurally; the latter condition was achieved by occluding one ear
      with a hearing protector. In PB word tests, the percent of correctly repeated
      words was scored. In the JFC task, the speech signal was adjusted by the listener
      to a level where he or she could just understand what was being said. This was
      expressed as a signal-to-noise (S/N) ratio. RESULTS: In both types of tests, the
      subjects achieved significantly better speech recognition scores in the binaural
      situations. In summary, compared with monaural conditions, the subjects achieved
      17% to 18% better speech recognition in PB tests, and in JFC tests a 2-to 3-dB
      lower S/N ratio in binaural conditions. CONCLUSION: These free field tests can be
      developed further as a clinical tool preoperatively and postoperatively to
      evaluate the effect of binaural hearing after ear surgery.

PMID- 11568670
TI  - Reliability of a rating scale for measuring speech intelligibility after
      pediatric cochlear implantation.
AB  - OBJECTIVE: To evaluate the reliability of the Speech Intelligibility Rating scale
      to monitor the speech intelligibility of deaf children who have received cochlear
      implants. STUDY DESIGN: A prospective study assessing the speech intelligibility
      of deaf children with cochlear implants by local and cochlear implant program
      speech and language therapists. SETTING: Pediatric tertiary referral center for
      cochlear implantation. PATIENTS AND METHODS: Fifty-four children were each rated
      by two speech and language therapists, one working with the child locally and the
      other working with the child at the cochlear implant program. All children were
      between 1.2 and 10.9 years of age at the time of implantation (median, 4.0
      years). The follow-up intervals ranged from before implantation to 9 years after
      implantation. MAIN OUTCOME MEASURE: Correlation coefficient, intraclass
      correlation coefficient, and kappa statistics were used to assess the
      interobserver reliability of the Speech Intelligibility Rating scale. RESULTS:
      Spearman rank correlation coefficient and intraclass correlation coefficient were
      0.82 with high statistical significance (p < 0.00001). Kappa statistical analysis
      revealed a moderate to substantial agreement between the ratings. This agreement
      also reached a high statistical significance (overall kappa = 0.53, p <
      0.000001). The Speech Intelligibility Rating scale was found to be able to
      discriminate speech intelligibility among subjects, and the ratings covaried with
      high consistency. CONCLUSION: The study found a high rate of agreement between
      observers when they used the Speech Intelligibility Rating scale to assess the
      speech intelligibility of deaf children after cochlear implantation. Because the
      scale presents information in a format that is understood by parents, local
      professionals, and health care purchasers, it will be useful to provide them with
      accessible information on speech intelligibility outcomes of deaf children who
      have received cochlear implants.

PMID- 11568671
TI  - Cochlear implants: is there any relationship between stimulation rates and
      adaptation?
AB  - OBJECTIVE: To determine the relationship between stimulation rate and adaptation
      in cochlear implant users. STUDY DESIGN: A prospective clinical study. SETTING:
      This study was conducted at Hacettepe University Medical Faculty, which is a
      tertiary care and cochlear implant center in Ankara, Turkey. PATIENTS: Seven
      patients (three women, four men) who were using Nucleus CI 24 M cochlear implants
      (Cochlear Corp., Lane Cove, NSW, Australia). Two of them had become deaf after
      developing language skills, and five had congenitally deafness. RESULTS: Six
      patients demonstrated no tone decay. Only one patient, who had congenital hearing
      loss, demonstrated tone decay at stimulation rates of 250, 500, 720, 900 pulses
      per second. There is no statistically significant relationship between the
      stimulation rate and the selected electrode. CONCLUSION: The majority of the
      cochlear implant patients sustained the perception of a continuous electrical
      signal for 1 minute at 5 to 10 current levels above threshold.

PMID- 11568672
TI  - Progressive fluctuant hearing loss, enlarged vestibular aqueduct, and cochlear
      hypoplasia in branchio-oto-renal syndrome.
AB  - OBJECTIVE: To study the results of petrosal bone imaging and audiometric long
      term follow-up of two patients with branchio-oto-renal (BOR) syndrome and relate
      them to the clinical features, including caloric responses. STUDY DESIGN:
      Longitudinal case study. SETTING: Tertiary referral center. PATIENTS: A father
      and son with the BOR syndrome. MAIN OUTCOME MEASURES: Both patients underwent
      imaging studies to detect and evaluate inner ear anomalies. Longitudinal
      audiometric analysis of the hearing threshold data over the previous 23 years was
      performed. Caloric tests were performed at various ages. RESULTS: The son had a
      short, wide internal acoustic canal, a hypoplastic cochlea, a plump vestibule,
      and a wide vestibular aqueduct on both sides; the semicircular canals and
      endolymphatic sac were of normal size. He showed progressive fluctuant
      sensorineural hearing loss. Caloric tests disclosed hyporeflexia on the left
      side. The father had a plump internal acoustic canal and hypoplastic cochlea on
      both sides. The left vestibule was hypoplastic, and the left vestibular aqueduct
      was marginally enlarged. He showed severe hearing impairment, without substantial
      progression or fluctuation, and caloric areflexia on the left side. CONCLUSION:
      These findings suggest a correlation between progressive fluctuant sensorineural
      hearing loss with caloric hypofunction and the presence of an enlarged vestibular
      aqueduct in the BOR syndrome. Additional longitudinal case studies are needed to
      further evaluate such a correlation.

PMID- 11568673
TI  - Objective tinnitus in children.
AB  - OBJECTIVE: To discuss the various symptoms and causes of objective tinnitus in
      children. STUDY DESIGN: Retrospective case review. PATIENTS: Five children who
      had audible signals emanating from their ears caused by audible spontaneous
      otoacoustic emissions, palatal myoclonus, arteriovenous malformation, and
      acoustic trauma. MAIN OUTCOME MEASURE: The tinnitus reported by the patients was
      linked to acoustic signals that could be measured objectively or heard by the
      examiner. RESULTS: Four of the five children had essentially normal hearing. The
      one child who demonstrated a hearing loss audiometrically was thought to have
      normal hearing sensitivity, but his intense roaring objective tinnitus appeared
      to mask his low-frequency thresholds. All five patients had measurable acoustic
      signals in the ear canal that matched the patients' descriptions of their
      tinnitus. CONCLUSION: The cases illustrate how the objective tinnitus was
      diagnosed and measured, how a treatment algorithm was applied, and the expected
      results of treatment. In addition, the cases provide support for the use of
      psychologic counseling throughout the examination and treatment of objective
      tinnitus in children.

PMID- 11568674
TI  - Characteristics of patients with gaze-evoked tinnitus.
AB  - OBJECTIVE: The authors describe symptoms and population characteristics in
      subjects who can modulate the loudness and/or pitch of their tinnitus by eye
      movements. STUDY DESIGN: Data were obtained by questionnaire. SETTING: The study
      was conducted at a university center and a tertiary care center. PATIENTS:
      Respondents had the self-reported ability to modulate their tinnitus with eye
      movements. RESULTS: Ninety-one subjects reported having gaze-evoked tinnitus
      after posterior fossa surgery involving the eighth nerve. Eighty-seven of them
      underwent removal of a vestibular schwannoma (acoustic neuroma), two had
      bilateral eighth nerve tumors (one underwent bilateral tumor removal; the other
      unilateral tumor removal), one underwent removal of a cholesteatoma, and one
      underwent removal of a glomus jugulare tumor. Seventeen subjects who had never
      had posterior fossa surgery reported gaze-evoked tinnitus. Of those with
      vestibular schwannomas, tumor size ranged from small (<2 cm) to large (>4 cm).
      The gender distribution was 48.3% male and 51.7% female. In 77% of patients, the
      gaze-evoked tinnitus was localized to the surgical ear or side of head; 21.8% had
      bilateral tinnitus that was louder in the surgical ear or side of head. In 86 of
      87 subjects, loudness of tinnitus changed with eye movement. Eye movement away
      from the central (eyes centered) position increased the loudness of tinnitus in
      all 86 subjects who responded to this question. Seventy-three of 85 (85.9%)
      patients indicated that pitch changed with eye movement, with pitch increasing in
      64/72 (88.9%) of them. Eighty-three of 87 (95.4%) patients reported total loss of
      hearing in the surgical ear. Seventy of 83 (84.3%) patients reported facial nerve
      problems immediately after surgery, 52 of 87 (60%) reported persistent facial
      weakness, and 16 of 87 (18.4%) patients reported persistent double vision. In
      those 17 subjects with gaze-evoked tinnitus and no posterior fossa surgery, the
      majority of respondents (14/17, 82.4%) were male. CONCLUSIONS: Gaze-evoked
      tinnitus after cerebellar pontine angle surgery is more common than was
      previously believed. In addition, posterior fossa surgery is not a prerequisite
      for the development of gaze-evoked tinnitus. It is likely that gaze-evoked
      tinnitus is a manifestation of functional reorganization. Gaze-evoked tinnitus
      could result from an unmasking of brain regions that respond to multiple
      stimulus/response modalities, and/or from anomalous cross-modality interactions,
      perhaps caused by collateral sprouting.

PMID- 11568675
TI  - Sensory cell damage in two-phase endolymphatic hydrops: a morphologic evaluation
      of a new experimental model by low-voltage scanning techniques.
AB  - HYPOTHESIS: The aim of this study was to create a more dynamic animal model of
      Meniere's disease combining multiple causes, such as the role of endocrine
      factors and endolymphatic sac dysfunction, that may mimic the fluctuant
      characteristics of Meniere's disease. BACKGROUND: Endolymphatic hydrops remains
      to be considered a pathologic substrate in the etiology of Meniere's disease. The
      classic guinea pig model of inducing hydrops by total destruction of the
      endolymphatic sac is a nonphysiologic rigid model of Meniere's disease. METHODS:
      The authors developed the two-phase endolymphatic hydrops model by inducing
      hydrops by mild chronic endolymphatic sac dysfunction, in combination with
      increased endolymph production by aldosterone. Sensory cell damage was evaluated
      by low-voltage field emission scanning microscopy. RESULTS: This study describes
      a wide spectrum of morphologic effects of the outer hair cells in radial
      gradients, in which most effects were observed in the third to second row of
      outer hair cells, and longitudinal gradients in which the most severe effects
      were observed in the apical turns. Most affected were the ears that underwent
      distal endolymphatic sac dissection followed by the administration of
      aldosterone. Damaging effects proceeded from degeneration and absence of short
      stereocilia of outer hair cells and even some inner hair cells in the apical
      turns, to stereociliary disarrangement and atrophy, followed by degeneration and
      absence of outer hair cells, which were replaced by supporting cells. CONCLUSION:
      The two-phase endolymphatic hydrops model seems to represent a functional model
      that may mimic the fluctuant characteristics of Meniere's disease and emphasizes
      the influence of multiple and coexisting hydrops-inducing influences.

PMID- 11568676
TI  - Recovery from vestibular ototoxicity.
AB  - OBJECTIVE: Determine whether subjects with documented vestibular ototoxicity
      recover vestibular function and, if so, investigate the recovery dynamics. STUDY
      DESIGN: Prospective and retrospective reviews and repeated measures. SETTING:
      Clinical research and technology center. SUBJECTS: Twenty-eight subjects who
      received vestibulotoxic medications were followed for at least 12 months after
      initial treatment. CONTROLS: Our subject sample was compared with a published
      database of normal individuals. INTERVENTIONS: All 28 subjects received
      systemically administered medications known to be ototoxic. The subjects'
      treating physicians controlled medication, dosage, and administration schedules.
      MAIN OUTCOME MEASURES: Tests of horizontal canal vestibulo-ocular function were
      performed. Subjects' auditory and vestibular symptoms were recorded. RESULTS:
      Eleven subjects (39%) showed changes in horizontal canal vestibulo-ocular gain
      constant (GC) and/or time constant (TC) consistent with vestibular ototoxicity.
      When tested 1 year after ototoxic drug administration, eight of the nine subjects
      who experienced ototoxic decrease in GC showed a recovery of GC to normal limits.
      Only one of the eight subjects who experienced ototoxic decrease in TC showed
      recovery of TC to within normal limits. Ototoxicity onset and recovery were
      independent of baseline vestibular function, and ototoxicity onset did not
      correlate with cumulative dose of ototoxic medication. There was no relationship
      between subjective symptoms and ototoxicity onset. CONCLUSIONS: Recovery of GC
      after vestibular ototoxicity is more commonly observed than recovery of TC.
      Because ototoxic changes developed and continued in an unpredictable time and
      manner in relation to ototoxic drug administration, we propose that once ototoxic
      changes in vestibulo-ocular reflex are detected, ototoxic medications should be
      discontinued as soon as possible.

PMID- 11568677
TI  - Tremor in otosurgery: influence of physical strain on hand steadiness.
AB  - BACKGROUND: The microscopically small middle ear structures require the
      otosurgeon to have a steady hand because instrument stability is a critical
      factor for a successful microsurgical procedure. Hand steadiness is mainly
      influenced by the tremor movements of the hand. The aim of this study was to
      measure hand tremor under simulated microsurgical conditions and to estimate the
      influence of different kinds of physical strain (e.g., physical exertion and hand
      exercise), as well as food abstinence and coffee consumption. Further, the effect
      of one-or two-handed manipulation and microsurgical experience was investigated.
      METHODS: The hand movements of 16 adult subjects were assessed during a defined
      manual manipulation using a stapes model to simulate microsurgical procedures. A
      laserinterferometric-based displacement technique was developed to measure tremor
      amplitude and frequency, as well as maximum displacement, to evaluate the
      subjects' fine motor skills. RESULTS: The mean tremor frequency across all
      measurements was 8.1 Hz and did not show any dependence on different kinds of
      physical strain. Two-handed manipulations showed significantly lower tremor
      amplitudes than one-handed performances. Tremor amplitude and maximum
      displacement did not change after hand exercise, food abstinence, and coffee
      consumption. However, after physical exertion, a significant increase in the
      tremor amplitude was found. Subjects with advanced microsurgical experience
      showed smaller tremor amplitudes for one-handed runs. CONCLUSION: The tremor data
      are interpreted as a recommendation to avoid physical exertion before
      microsurgery. In cases of absolute necessity for hand steadiness, two-handed
      manipulations are preferable. Further, hand steadiness might be improved by
      microsurgical training and experience.

PMID- 11568678
TI  - Otologic manifestations of Chiari I malformation.
AB  - OBJECTIVE: To assess the prevalence of otologic symptoms in patients undergoing
      surgical decompression for symptomatic Chiari I malformation. STUDY DESIGN: Cross
      sectional, prospective, nonrandomized. SETTING: Urban tertiary referral center.
      PATIENTS: Patients with Chiari I malformation before surgical intervention.
      INTERVENTIONS: None. MAIN OUTCOME MEASURE: Results of completed questionnaire.
      RESULTS: Sixteen consecutive patients with Chiari I malformation completed the
      self-administered questionnaire. Eighty-one percent of patients reported episodic
      aural fullness, 81% reported tinnitus, 69% reported vertigo, and 56% reported
      fluctuating hearing loss. Headaches were reported as frequently as aural fullness
      and tinnitus. CONCLUSIONS: Most patients with Chiari I malformation have symptoms
      that mimic primary otologic pathologic changes. The existence of common
      pathophysiologic mechanisms is proposed.

PMID- 11568679
TI  - Update on conservative management of acoustic neuroma.
AB  - OBJECTIVE: To update the authors' experience with conservative management of
      acoustic neuromas. STUDY DESIGN: Retrospective chart review. SETTING: Private
      practice and tertiary care referral setting. INTERVENTION: Of 600 patients with
      acoustic neuroma, 102 were treated with the "wait and scan" treatment option. At
      least two magnetic resonance imaging scans were required of all patients. MAIN
      OUTCOME MEASURES: Change in tumor size over time was evaluated, as were clinical
      symptoms: hearing status, tinnitus, balance disturbance, aural fullness, vertigo,
      headache, and facial pain, numbness, or weakness. RESULTS: Of 102 patients, the
      average follow-up time interval was 28.5 months. Forty-five (44%) of 102 patients
      demonstrated a change in tumor size: an average total growth of 2.17 mm per year.
      In the remaining 54 patients (53%), no growth was demonstrated during a mean
      follow-up of 28.5 months. Three patients demonstrated actual tumor shrinkage. Of
      the 102 patients receiving conservative treatment, 85 (84%) reported hearing
      loss, 67 (66%) tinnitus, 37 (36%) balance disturbance, 29 (28%) aural fullness,
      28 (27%) vertigo, 7 (7%) headache, 4 (4%) facial numbness, 2 (2%) facial
      weakness, and 0 (0%) facial pain. CONCLUSION: Conservative management-"wait and
      scan"-for selected patients with acoustic neuroma is a reasonable choice of
      management instead of radiation or microsurgery. In some situations the
      individual morbidities associated with surgery or radiation make those treatments
      not in the patient's best interests. A third option is necessary in patients who
      cannot or do not wish to undergo those other treatments.

PMID- 11568680
TI  - Acoustic neuroma surgery outcomes.
AB  - OBJECTIVE: The outcomes of surgery for acoustic neuromas have improved
      dramatically since the development of modern surgical techniques, the operating
      microscope, magnetic resonance imaging (MRI), and cranial nerve monitoring. The
      goals of acoustic neuroma surgery are now preservation of facial nerve function
      and, when feasible, hearing preservation. Many large series do not report
      standardized hearing and facial function grading, and they include patients who
      did not benefit from the most modern techniques. The purpose of this study was to
      present the results of acoustic neuroma surgery using the most modern techniques
      and equipment, using standardized grading systems. STUDY DESIGN: Retrospective
      review. SETTING: Tertiary referral center. PATIENTS: 97 patients who underwent
      surgical removal of acoustic neuromas from 1992 to 1998. INTERVENTION: All
      patients underwent acoustic neuroma surgery and had preoperative audiograms and
      MRI with contrast. In addition, all patients had preoperative and postoperative
      facial function graded by the House-Brackmann scale and intraoperative facial
      nerve monitoring. Hearing preservation was attempted in patients with tumors of
      any size who had preoperative function of grade A or B according to the Committee
      on Hearing and Equilibrium guidelines for reporting results of acoustic neuroma
      surgery. MAIN OUTCOME MEASURES: Hearing preservation was considered successful if
      the patient retained serviceable hearing grade A or B. House-Brackmann grade 1 or
      2 was considered excellent facial function. Complications were recorded. RESULTS:
      Facial nerve integrity was preserved in 96 of 97 patients (99%). Eight of 8
      (100%) patients with intracanalicular tumors had excellent facial nerve function
      (HB 1-2). Fifty-two of 55 (95%) of patients with small tumors had excellent
      facial nerve function, and 15 of 24 (63%) with medium tumors had HB grade 1-2.
      Hearing was preserved in 29% of patients with tumors under 2 cm. The overall
      complication rate was 20%; cerebrospinal fluid leak was the most common.
      CONCLUSION: These results show that with modern imaging and surgical techniques,
      acoustic neuroma surgery is extremely safe and outcomes are very good. Surgery
      remains the treatment of choice for most tumors until alternative therapies, such
      as gamma knife, use uniform grading scales and show long-term facial and hearing
      results.

PMID- 11568681
TI  - The transcochlear approach revisited.
AB  - OBJECTIVE: To evaluate the indications for, techniques used in, and patient
      outcomes after surgery with the transcochlear approach in the treatment of
      petroclival tumors. METHODS: Retrospective review of 24 cases between 1985 and
      1995 at the House Ear Clinic (Los Angeles, CA, U.S.A.). RESULTS: Meningioma was
      the most common tumor. Complete removal was achieved in 82% of tumors after one
      or two-stage surgeries (average follow-up time, 36 months). The second-stage
      surgery was a middle fossa transpetrous approach. Most patients had some degree
      of facial nerve dysfunction immediately after surgery, and 12 of 20 patients
      subsequently improved to House-Brackmann Grade III or better. Fifty-nine percent
      of patients had permanent neurologic sequelae because of either the surgery or
      their disease. CONCLUSION: The transcochlear approach is best suited to treating
      petroclival intradural tumors that extend ventrally to the brainstem in patients
      without serviceable hearing. Temporary facial weakness is expected as a result of
      posterior facial nerve transposition.

PMID- 11568682
TI  - Elevation of internal auditory canal pressure by vestibular schwannomas.
AB  - OBJECTIVE: The exact mechanism of hearing loss, the most common presenting
      symptom in patients with vestibular schwannomas, remains unclear. To test whether
      increased pressure in the internal auditory canal from tumor growth is
      responsible for this clinical finding, the intracanalicular pressure in patients
      harboring these tumors was measured. STUDY DESIGN: Prospective study. SETTING:
      Tertiary referral hospital. PATIENTS: Fifteen consecutive patients undergoing a
      retrosigmoid approach for resection of vestibular schwannomas were included in
      the study. INTERVENTION: The intracanalicular pressure in every patient was
      measured by introducing a pressure microsensor into the internal auditory canal.
      The pressure readings, which were performed before tumor resection, were then
      correlated with tumor size and respective preoperative hearing status. RESULTS:
      Placement of the pressure monitor into the internal auditory canal revealed a
      biphasic waveform in every patient. Whereas the mean intracanalicular pressure
      was 20 mm Hg, there was significant variability among patients (range, 1-45 mm
      Hg). The intracanalicular pressure directly correlated with the amount of tumor
      in the internal auditory canal (r > 0.63, p < 0.012) but not with the total tumor
      size (r </= 0.40, p > 0.075). Furthermore, eight patients with class A
      preoperative hearing (American Academy of Otolaryngology-Head and Neck Surgery
      classification) had lower intracanalicular pressures than did five patients with
      class B hearing (16 +/- 5 vs. 28 +/- 4). Although this observation suggested an
      inverse correlation between the intracanalicular pressure and hearing function,
      the difference between the two groups was not statistically significant (p =
      0.14). CONCLUSION: Pressure on the cochlear nerve as a result of tumor growth in
      the internal auditory canal may be responsible for hearing loss in patients with
      vestibular schwannomas. Modification of surgical techniques to address the
      elevated intracanalicular pressure may be beneficial in improving hearing
      preservation in these patients.

PMID- 11568683
TI  - Posttraumatic pseudo-cerebrospinal fluid rhinorrhea.
AB  - OBJECTIVE AND HYPOTHESIS: Posttraumatic clear rhinorrhea should result in
      immediate concern for a suspected cerebrospinal fluid (CSF) fistula in patients
      with skull base injuries, including surgical trauma. However, in addition to CSF
      rhinorrhea, the differential diagnosis may also include postinjury autonomic
      dysfunction. Pseudo-cerebrospinal fluid rhinorrhea (PCSFR) is a term used to
      describe rhinorrhea resulting from injury to preganglionic parasympathetic fibers
      supplying the sphenopalatine ganglion. This ganglion plays a critical role in
      this pathway secondary to its anatomic course and physiologic function.
      Differentiating between PCSFR and true CSF rhinorrhea can be a diagnostic
      challenge and may result in unnecessary and costly invasive testing and
      treatment. CASE STUDY: The authors present an illustrative case of noniatrogenic
      posttraumatic PCSFR in a previously healthy patient who experienced a head injury
      in a horseback riding accident. DISCUSSION: Features of PCSFR include a history
      of skull base surgery or trauma with involvement of autonomic structures in this
      region, rhinorrhea within months or years after injury, decreased lacrimation on
      the involved side, absence of clinical signs of meningitis, and a negative beta2
      transferrin test result. Management of PCSFR is aimed at restoring the normal
      autonomic homeostasis in the nasal cavity. Treatment options include topical
      medicines such as anticholinergics and the various surgical procedures aimed at
      disruption of parasympathetic preganglionic fibers proximal to or at the
      sphenopalatine ganglion. CONCLUSION: This case and its diagnosis and management
      provide an additional mechanism of PCSFR, a clinical entity that must be
      considered in the evaluation of all patients with previous skull base trauma.

PMID- 11568684
TI  - Clival chordoma mimicking a trigeminal schwannoma.

PMID- 11568685
TI  - Scheibe (cochleosaccular) dysplasia.

PMID- 11568686
TI  - Chronic myringitis: prevalence, presentation, and natural history.

PMID- 11568687
TI  - A century of eighth nerve surgery.

PMID- 11568688
TI  - Marginal candidates in cochlear implantation.

PMID- 11568690
TI  - Five-year results from chemonucleolysis with chymopapain or collagenase: a
      prospective randomized study.
AB  - STUDY DESIGN: A 5-year clinical follow-up assessment of a prospective randomized
      study of chemonucleolysis using chymopapain (4000 IU) or collagenase (400 ABC
      units) was performed. SUMMARY OF BACKGROUND DATA: Intradiscal therapy can be
      performed for patients with contained discs by chemonucleolysis, percutaneous
      discectomy, or laser ablation. The oldest intradiscal therapy is chemonucleolysis
      with chymopapain. OBJECTIVE: The purpose of this study was to compare
      prospectively the efficacy of chymopapain and collagenase for intradiscal
      injection. METHODS: In this study, 100 patients with indication for intradiscal
      therapy were prospectively randomized to treatment with either chymopapain or
      collagenase. All the injections were performed by the double-needle technique
      with the patient under general anesthesia. The mean age of the patients was 35.5
      years in the chymopapain group and 38 years in the collagenase group. An equal
      number of injections was performed at L4-L5 and L5-S1. RESULTS: After 5 years,
      good and excellent results were observed in 72% of the chymopapain group and 52%
      of the collagenase group when the surgically treated and lost patients were
      graded as poor. Using a scale of 0 (no pain) to 10 (intractable pain), the pain
      level dropped from 8.5 to 0.7 in the chymopapain group and from 8.6 to 0.9 in the
      collagenase group. Microdiscectomy at the injected level was required for 23
      patients (14 in the collagenase group and 9 in the chymopapain group).
      CONCLUSIONS: After 5 years, no deterioration had occurred, as compared with the 1
      year follow-up assessment. Chymopapain has proved to be safe, with one minor
      anaphylactic reaction, and effective even over the long term. Collagenase may
      need further study and cannot be recommended at this time.

PMID- 11568692
TI  - Excitotoxic model of post-traumatic syringomyelia in the rat.
AB  - STUDY DESIGN: A rat model was developed to elucidate the role of excitatory amino
      acids and spinal subarachnoid block in the genesis of post-traumatic
      syringomyelia. This excitotoxic model produces intramedullary cavities rather
      than the dilation of the central canal (canalicular syringomyelia) created by
      previous animal models. OBJECTIVES: To produce extracanalicular cysts in the rat
      spinal cord with quisqualic acid, a potent agonist of multiple excitatory amino
      acid receptors, and to compare the effects of excitotoxic injury only with that
      of excitotoxic injury and subarachnoid block with kaolin. SUMMARY OF BACKGROUND
      DATA: In post-traumatic syringomyelia, primary injury and excitotoxic cell death
      secondary to elevated levels of excitatory amino acids may initiate a pathologic
      process leading to the formation of spinal cavities. Subarachnoid block by
      arachnoiditis may promote enlargement of the cavities. METHODS: Three control
      rats received a unilateral injection of normal saline into the spinal cord, and
      another five rats received an injection of kaolin into the spinal subarachnoid
      space. Quisqualic acid was injected unilaterally into the spinal cord of 20 rats,
      and 13 additional rats received a unilateral injection of quisqualic acid into
      the spinal cord after injection of kaolin into the subarachnoid space. Histologic
      and immunocytochemical assessments were undertaken. RESULTS: In the control
      groups, no parenchymal cyst developed in any of the animals. Spinal cord cyst
      formation was observed in 16 of 19 animals in the quisqualic acid groups, but no
      cysts exceeding two segments in the length of the spinal cord developed in any of
      the rats. Much larger cavities were seen in 9 of 11 animals in the group with
      quisqualic acid and kaolin, and cysts exceeding two segments developed in all 9
      of these (9/11; 82%). CONCLUSIONS: In post-traumatic syringomyelia, excitotoxic
      cell death occurring secondarily to elevated levels of excitatory amino acids may
      contribute to the pathologic process leading to the formation of spinal cord
      cysts. Subarachnoid block by arachnoiditis is likely to cause enlargement of the
      cavity.

PMID- 11568693
TI  - Biomechanical comparison of cervical spine interbody fusion cages.
AB  - STUDY DESIGN: An in vitro biomechanical study of cervical spine interbody fusion
      cages using a sheep model was conducted. OBJECTIVES: To evaluate the
      biomechanical effects of cervical spine interbody fusion cages, and to compare
      three different cage design groups. SUMMARY AND BACKGROUND DATA: Recently, there
      has been a rapid increase in the use of cervical spine interbody fusion cages as
      an adjunct to spondylodesis. These cages can be classified into three design
      groups: screw, box, or cylinder designs. Although several comparative
      biomechanical studies of lumbar interbody fusion cages are available,
      biomechanical data for cervical spine constructs are lacking. Additionally, only
      limited data are available concerning comparative evaluation of different cage
      designs. METHODS: In this study, 80 sheep cervical spines (C2-C5) were tested in
      flexion, extension, axial rotation, and lateral bending with a nondestructive
      stiffness method using a nonconstrained testing apparatus. Three-dimensional
      displacement was measured using an optical measurement system (Qualysis).
      Complete discectomy (C3-C4) was performed. Cervical spine interbody fusion cages
      were implanted according to manufacturers' information. Eight spines in each of
      the the following groups were tested: intact, autologous iliac bone graft, two
      titanium screws (Novus CTTi; Sofamor Danek, Koln, Germany), two titanium screws
      (BAK-C 8 mm; Sulzer Orthopedics, Baar, Switzerland), one titanium screw (BAK-C 12
      mm; Sulzer Orthopedics), carbon box (Novus CSRC; Sofamor Danek), titanium box
      (Syncage; Synthes, Bochum, Germany), titanium mesh cylinder (Harms; DePuy
      Acromed, Sulzbach, Germany), titanium cylinder (MSD; Ulrich, Ulm, Germany), and
      titanium cylinder (Kaden; BiometMerck, Berlin, Germany). The mean apparent
      stiffness values were calculated from the corresponding load-displacement curves.
      Additionally, cage volume and volume-related stiffness was determined. RESULTS:
      After cervical spine interbody fusion cage implantation, flexion stiffness
      increased, as compared with that of the intact motion segment. On the contrary,
      rotation stiffness decreased after implantation of a cervical spine interbody
      fusion cage, except for the Novus CSRC, Syncage, and Kaden-Cage. If two screws
      were inserted (Novus CTTi and BAK-C 8 mm), there was no significant difference in
      flexion stiffness between screw and cylinder design groups. If one screw was
      inserted (BAK-C 12 mm), flexion stiffness was higher for cylinder designs (P <
      0.05). Extension and bending stiffness were always higher with cylinder designs
      (P < 0.05). Volume-related stiffness for flexion extension and bending was
      highest for the Harms cage (P < 0.05). There was no difference for rotation
      volume-related stiffness between Harms and Syncage. CONCLUSIONS: The
      biomechanical results indicate that design variations in screw and cylinder
      design groups are of little importance. In this study, however, cages with a
      cylinder design were able to control extension and bending more effectively than
      cages with a screw design.

PMID- 11568694
TI  - Using cineradiography for continuous dynamic-motion analysis of the lumbar spine.
AB  - STUDY DESIGN: Cineradiography was used to analyze continuous dynamic motion in
      the lumbar spine. OBJECTIVES: To identify motion patterns of the lumbar spine in
      asymptomatic volunteers and symptomatic patients with L4 degenerative
      spondylolisthesis, and to use the findings to discuss segmental instability in
      this disorder. SUMMARY OF BACKGROUND DATA: The use of radiographic findings to
      assess lumbar spine instability remains controversial. Although some studies have
      reported on lumbar kinematics during actual movement, the motion patterns in
      asymptomatic volunteers and symptomatic patients with L4 degenerative
      spondylolisthesis have not been fully clarified. METHODS: While asymptomatic
      volunteers (n=20; mean age, 27; control group) and symptomatic patients with L4
      degenerative spondylolisthesis (n=41; mean age, 63; degenerative
      spondylolisthesis [DS] group) flexed from a sitting neutral position and back to
      the neutral position (flexion course), cineradiography was used to record lateral
      segmental lumbar motions. Twelve frames were selected during the flexion course,
      and flexion-extension angle (f-e angle) and translation in the sagittal plane
      were measured at each motion segment (L2-L3, L3-L4, L4-L5, and L5-S1). The DS
      group was classified into 2 subgroups according to percentage of slip: DS group
      I, with a slip equal to or less than 15%; and DS group II, with a slip of more
      than 15%. The motion pattern was compared between the groups. RESULTS: In the
      control group, f-e angle and translation at the L2-L3, L3-L4, and L4-L5 segments
      moved simultaneously, although the L5-S1 segment showed an initial delay. The
      amount of f-e angle and translation changed almost symmetrically. In both f-e
      angle and translation, the L4-L5 segment showed a large motion pattern. In DS
      group I (n=21), the L4-L5 segment showed a large motion pattern in f-e angle and
      an intermediate motion pattern in translation. In DS group II (n=20), the L4-L5
      segment showed an intermediate motion pattern in f-e angle, and a small motion
      pattern in translation. The relative range of f-e angle at the L4-L5 segment had
      the largest range in DS group I, and the relative translation showed a serial
      decrease from the control group through DS group II. A significant correlation
      between f-e angle and translation (harmonious motion pattern) was noted at the L2
      L3, L3-L4, and L4-L5 segments in the control group. The harmonious motion pattern
      at the L4-L5 segment was significantly less in the DS group than in the control
      group. The loss of harmonious motion pattern (disordered motion pattern) at L4-L5
      was well-revealed in the DS group II. CONCLUSIONS: Motion analyses using
      cineradiography helped to explain the phenomena of lumbar spine kinematics. Based
      on continuous dynamic-motion analysis with cineradiography, large f-e angle and
      disordered motion pattern during the flexion-backward course in the DS group I
      was considered to be caused by segmental instability. The decreased translation
      and disordered motion pattern throughout the flexion course in the DS group II
      was considered to be caused by restabilization.

PMID- 11568695
TI  - Magnetic resonance imaging analysis of soft tissue disruption after flexion
      distraction injuries of the subaxial cervical spine.
AB  - STUDY DESIGN: A retrospective study was performed with the use of magnetic
      resonance imaging to evaluate the type and degree of soft tissue disruption
      associated with flexion-distraction injuries of the subaxial spine. OBJECTIVE: To
      determine what soft tissue structures are injured in flexion-distraction injuries
      of the subaxial spine. SUMMARY OF BACKGROUND DATA: Prior published reports of
      unilateral and bilateral cervical facet dislocations have described the analyzed
      mechanisms and biomechanics of this injury subtype. No retrospective magnetic
      resonance imaging analysis of associated soft tissue disruption has been
      documented. METHODS: Magnetic resonance imaging evaluations of the cervical spine
      were obtained for all patients with a flexion-distraction injury, Stages 2
      (unilateral facet dislocation) and 3 (bilateral facet dislocation), between
      September 1994 and May 1998. Two neuroradiologists, blinded to both clinical and
      radiographic findings, graded all the soft tissue structures for evidence of
      attenuation or disruption. The soft tissue structures were graded on a scale of 1
      (intact), 2 (indeterminate), or 3 (disrupted). RESULTS: For this study, 48
      patients satisfied the inclusion criteria: 25 with unilateral facet dislocation
      and 23 with bilateral facet dislocation. Disruption to the posterior musculature,
      interspinous ligament, supraspinous ligament, facet capsule, ligamentum flavum,
      and posterior and anterior longitudinal ligaments was found in a statistically
      significant number of patients with bilateral facet dislocation. For most of
      these structures, disruption was found to be statistically significant in
      patients with a unilateral facet dislocation, except for the posterior
      longitudinal ligament, in which significance was not consistently demonstrated
      using 95% confidence intervals in the binomial testing. In a comparison between
      unilateral and bilateral facet dislocations using a two-sided Fisher's exact
      test, it was found that disruption to the anterior and posterior longitudinal
      ligaments and the left facet capsule were statistically significant, with all
      three more prominent in bilateral facet dislocation. A multivariate analysis
      between unilateral and bilateral facet dislocations showed that disruption to the
      anterior longitudinal ligament was associated significantly with a bilateral
      facet dislocation. Disc disruption was found to be associated significantly with
      both injury types, but was more common in bilateral facet dislocation, although
      this difference in intergroup comparisons was not statistically significant.
      CONCLUSIONS: Unilateral and bilateral facet dislocations of the subaxial spine
      are associated with damage to numerous soft tissue structures that provide
      stability to the lower cervical spine. Damage to the posterior longitudinal
      ligament did not occur consistently in unilateral facet dislocations. Bilateral
      facet dislocations were associated significantly with disruption to the posterior
      and anterior longitudinal ligaments and left facet capsule, as compared with
      unilateral facet dislocations. Magnetic resonance imaging allows visualization of
      these disruptions.

PMID- 11568697
TI  - Magnetic resonance classification of lumbar intervertebral disc degeneration.
AB  - STUDY DESIGN: A reliability study was conducted. OBJECTIVES: To develop a
      classification system for lumbar disc degeneration based on routine magnetic
      resonance imaging, to investigate the applicability of a simple algorithm, and to
      assess the reliability of this classification system. SUMMARY OF BACKGROUND DATA:
      A standardized nomenclature in the assessment of disc abnormalities is a
      prerequisite for a comparison of data from different investigations. The
      reliability of the assessment has a crucial influence on the validity of the
      data. Grading systems of disc degeneration based on state of the art magnetic
      resonance imaging and corresponding reproducibility studies currently are sparse.
      METHODS: A grading system for lumbar disc degeneration was developed on the basis
      of the literature. An algorithm to assess the grading was developed and optimized
      by reviewing lumbar magnetic resonance examinations. The reliability of the
      algorithm in depicting intervertebral disc alterations was tested on the magnetic
      resonance images of 300 lumbar intervertebral discs in 60 patients (33 men and 27
      women) with a mean age of 40 years (range, 10-83 years). All scans were analyzed
      independently by three observers. Intra- and interobserver reliabilities were
      assessed by calculating kappa statistics. RESULTS: There were 14 Grade I, 82
      Grade II, 72 Grade III, 68 Grade IV, and 64 Grade V discs. The kappa coefficients
      for intra- and interobserver agreement were substantial to excellent:
      intraobserver (kappa range, 0.84-0.90) and interobserver (kappa range, 0.69
      0.81). Complete agreement was obtained, on the average, in 83.8% of all the
      discs. A difference of one grade occurred in 15.9% and a difference of two or
      more grades in 1.3% of all the cases. CONCLUSION: Disc degeneration can be graded
      reliably on routine T2-weighted magnetic resonance images using the grading
      system and algorithm presented in this investigation.

PMID- 11568698
TI  - Back pain reporting pattern in a Danish population-based sample of children and
      adolescents.
AB  - STUDY DESIGN: A cross-sectional survey of 806 pupils in Odense, Denmark was
      performed. This survey included children and adolescents ages 8 to 10 and 14 to
      16 years obtained through two-stage cluster sampling from schools stratified
      according to school type, location, and socioeconomic character of the uptake
      area. OBJECTIVES: To establish the 1-month prevalence of neck, middle back, and
      low back pain and the consequences this disorder may have in relation to age and
      gender. SUMMARY OF BACKGROUND DATA: The differences in definitions of back pain
      and the variety of age groups included in previous studies make it difficult to
      draw clear conclusions about the onset of pain for various spinal regions in the
      young. METHODS: Information on back pain within the preceding month, obtained
      through a standardized interview of 481 children and 325 adolescents, was
      categorized according to area of pain, age, and gender. The consequences of back
      pain also were studied. RESULTS: The 1-month prevalence of back pain was 39%.
      Thoracic pain is most common in childhood, whereas thoracic pain and lumbar pain
      are equally common in adolescence. Neck pain and pain in more than one area of
      the spine are rare in both age groups. No gender differences were found. Of those
      who had back pain, 38% also reported some type of consequence, usually either
      visits to a medical physician or diminished physical activities. CONCLUSIONS: For
      clinical and research purposes, neck pain, middle back pain, and low back pain in
      childhood should be regarded as three specific entities. In future research the
      data for different age groups should be reported separately.

PMID- 11568699
TI  - Subjective health measure used on Chinese patients with neck pain in Hong Kong.
AB  - STUDY DESIGN: A prospective observational study was conducted on the use of the
      Chinese version of the Northwick Park Neck Pain Questionnaire. OBJECTIVE: To
      examine the reliability, validity, and responsiveness of the Chinese version of
      the Northwick Park Neck Pain Questionnaire in Chinese patients with neck pain in
      Hong Kong. SUMMARY OF BACKGROUND DATA: There is increasing recognition that
      patient perspectives are essential both in making medical decisions and in
      judging the treatment outcomes. A valid Chinese version of a neck disability
      index questionnaire is urgently needed for effective and reliable evaluation of
      the treatment outcomes for patients with neck pain. METHODS: Two samples with 532
      consecutive adult patients with neck pain from seven physiotherapy outpatient
      departments in Hong Kong who completed the Northwick Park Neck Pain Questionnaire
      were observed and measured at different intervals: at the beginning of
      physiotherapy, at 7 days, at 3 weeks, and 6 weeks after physiotherapy. RESULTS:
      The questionnaire had good content validity, very good test-retest reliability,
      and internal consistency (intraclass correlation coefficient, 0.95; Cronbach's
      alpha, 0.87). It also had good validity (Spearman correlation coefficient of 0.59
      when the score was correlated with that of a generic 42-item Chinese health
      questionnaire) and good responsiveness (effect size of 1.11 at week 6 after
      treatment began). CONCLUSIONS: The Chinese version of the Northwick Park Neck
      Pain Questionnaire has been shown to demonstrate very good content validity, a
      high degree of test-retest reliability, and internal consistency. It also
      exhibited good construct validity and high sensitivity to changes in severity
      over time.

PMID- 11568701
TI  - Interobserver and intraobserver reliability of the japanese orthopaedic
      association scoring system for evaluation of cervical compression myelopathy.
AB  - STUDY DESIGN: The inter- and intraobserver reliabilities of an assessment scale
      for cervical compression myelopathy were examined statistically. This scoring
      system consists of seven categories: motor function of fingers, shoulder and
      elbow, and lower extremity; sensory function of upper extremity, trunk and lower
      extremity; and function of the bladder. It evaluates the severity of myelopathy
      by allocating points based on degree of dysfunction in each category. OBJECTIVES:
      To determine the inter- and intraobserver reliabilities of the revised scoring
      system (17 - 2 points) for cervical compression myelopathy proposed by the
      Japanese Orthopedic Association. SUMMARY OF BACKGROUND DATA: Several scales to
      assess clinical outcome from treatment of cervical compression myelopathy have
      been proposed. Most of these scales include items evaluated by observers.
      However, no system, including the Japanese Orthopedic Association scoring system,
      has yet been validated in terms of interobserver reliability. METHODS: From five
      different university hospitals, 10 spine surgery specialists, 10 orthopedic
      surgeons who had just passed the board examination of the Japanese Orthopedic
      Association, and 13 residents in the first or second year of orthopedic residency
      programs were chosen. The participants in this study were 29 patients with
      myelopathy secondary to ossification of the posterior longitudinal ligament
      selected from five participating university hospitals. Several surgeons
      interviewed each patient twice at intervals of 1 to 6 weeks. Inter- and
      intraobserver reliabilities of the total score for all categories were evaluated
      by the intraclass correlation coefficient. The extension of the kappa coefficient
      of Kraemer also was calculated for each category to assess reliability of
      multivariate categorical data. RESULTS: The interobserver reliability of the
      total score for the first interview (intraclass correlation coefficient = 0.813)
      and the intra- and interobserver reliabilities of the total score (intraclass
      correlation coefficient = 0.826) were high. The level of experience and the
      hospital slightly affected the reliability of the Japanese Orthopedic Association
      scoring system. The kappa values for intraobserver data generally were high in
      each category, whereas the kappa values for interobserver data were relatively
      low for the categories of shoulder-elbow motor function and lower extremity
      sensory function. CONCLUSIONS: The inter- and intraobserver reliabilities of the
      Japanese Orthopedic Association scoring system for cervical myelopathy were high,
      suggesting that this system is useful for assessment of cervical myelopathy in
      comparative studies of treatment.

PMID- 11568702
TI  - High quantitative job demands and low coworker support as risk factors for neck
      pain: results of a prospective cohort study.
AB  - STUDY DESIGN: A 3-year prospective cohort study among 1334 workers was conducted.
      OBJECTIVE: To determine whether the work-related psychosocial factors of
      quantitative job demands, conflicting job demands, skill discretion, decision
      authority, supervisor support, coworker support, and job security are risk
      factors for neck pain. SUMMARY OF BACKGROUND DATA: Among the various risk factors
      for neck pain, work-related psychosocial factors play a major role. Previous
      studies on risk factors for neck pain often had a cross-sectional design, and did
      not take both physical and psychosocial factors into account. METHODS: At
      baseline, data on work-related psychosocial factors were collected by means of a
      questionnaire. During the 3-year follow-up period, data on the occurrence of neck
      pain were collected by means of postal questionnaires. Individuals without neck
      pain at baseline were selected for the analyses. Cox regression analysis was
      applied to examine the relation between the work-related psychosocial factors and
      the cumulative incidence of neck pain. Adjustments were made for various physical
      factors and individual characteristics. RESULTS: The analysis included 977
      patients. Altogether, 141 workers (14.4%) reported that they had experienced neck
      pain at least once during the 3-year follow-up period. The relation of neck pain
      to high quantitative job demands (relative risk [RR], 2.14; 95% confidence
      interval [CI], 1.28-3.58) and low coworker support (RR, 2.43; 95% CI, 1.11-5.29)
      was statistically significant. An increased risk was found for low decision
      authority in relation to neck pain (RR, 1.60; 95% CI, 0.74-3.45), but this
      relation was not statistically significant. CONCLUSIONS: High quantitative job
      demands and low coworker support are independent risk factors for neck pain.
      There are indications that another risk factor for neck pain is low decision
      authority.

PMID- 11568704
TI  - Three-dimensional isometric strength of neck muscles in humans.
AB  - STUDY DESIGN: Three-dimensional moments were measured experimentally during
      maximum voluntary contractions of neck muscles in humans. OBJECTIVES: To
      characterize the maximum moments with attention paid to subject size and gender,
      to calculate moments at different locations in the neck, and to quantify the
      relative magnitudes of extension, flexion, lateral bending, and axial rotation
      moments. SUMMARY OF BACKGROUND DATA: Few studies of neck strength have measured
      moments in directions other than extension, and it is difficult to compare
      results among studies because moments often are resolved at different locations
      in the cervical spine. Further, it is not clear how subject size, gender, and
      neck geometry relate to variations in the moment-generating capacity of neck
      muscles. METHODS: Maximum moments were measured in 11 men and 5 women with an
      average age of 31 years (range, 20-42 years). Anatomic landmarks were digitized
      to resolve moments at different locations in the cervical spine. RESULTS: When
      moments were resolved about axes through the midpoint of the line between the C7
      spinous process and the sternal notch, the maximum moments were as follows:
      extension (men, 52 +/- 11 Nm; women, 21 +/- 12 Nm), flexion (men, 30 +/- 5 Nm;
      women, 15 +/- 4 Nm), lateral bending (men, 36 +/- 8 Nm; women, 16 +/- 8 Nm), and
      axial rotation (men 15 +/- 4; women, 6 +/- 3) Nm). The magnitudes of extension,
      flexion, and lateral bending moments decreased linearly with vertical distance
      from the lower cervical spine to the mastoid process. CONCLUSIONS: Moments in
      three dimensions were quantified with regard to subject size and location along
      the cervical spine. These data are needed to characterize neck strength for
      biomechanical analysis of normal and pathologic conditions.

PMID- 11568706
TI  - Polyurethane real-size models used in planning complex spinal surgery.
AB  - STUDY DESIGN: The application of polyurethane real-size models for planning and
      performing complex spinal surgery is described. OBJECTIVE: To determine the
      feasibility of using polyurethane real-size models to plan osteotomies,
      resections, and designs of custom-made spinal implants in complex spinal surgery.
      SUMMARY OF BACKGROUND DATA: In selected patients with complex spinal pathology,
      exact planning of the surgical procedure is not possible using current imaging
      methods. In these cases, real-size spinal models would be desirable to enhance
      pre- and perioperative planning by visual and tactile feedback, and to improve
      the production of custom-made spinal implants. METHODS: A real-size spinal model
      of six patients was produced from hardened polyurethane foam on the basis of data
      from contiguous computer tomography slices. In two patients, the models were used
      to plan correction osteotomies and resections, with the assistance of image
      guided surgery in one of the patients. In four patients, the models were used to
      plan tumor resections and to produce custom-made spinal implants. RESULTS: In all
      the patients, the surgical procedure could be performed exactly according to the
      preplanned intervention. The polyurethane real-size models provided essential and
      additional information by direct visual and tactile feedback. They allowed in
      vitro testing of custom-made spinal implants with a perfect fit. CONCLUSIONS:
      Real-size spinal models made from polyurethane foam can be used to provide
      excellent understanding of the complex spinal pathology in highly selected
      patients. These models allow complex spinal surgery with a more predictable
      outcome.

PMID- 11568705
TI  - Influences of nonspecific low back pain on three-dimensional lumbar spine
      kinematics in locomotion.
AB  - STUDY DESIGN: A three-dimensional kinematic analysis of lumbar spinal movements
      with an ultrasonic measuring system was used to distinguish patients with chronic
      low back pain from those without such pain. OBJECTIVES: To investigate the
      effects of chronic low back pain on the three-dimensional movements of the lumbar
      spine, and to identify variables that would allow discrimination among patients
      with chronic low back pain and control subjects. SUMMARY OF BACKGROUND DATA: To
      the authors' knowledge, no previous studies have described or identified altered
      spinal and pelvic gait kinematics caused by nonspecific chronic low back pain in
      all anatomic planes. METHODS: In this study, 34 participants with chronic low
      back pain and 22 subjects without such pain were monitored during treadmill gait.
      Data from the measuring system operating at 30 Hz were low-pass filtered and
      normalized to a percentage of the gait cycle. RESULTS: Cross-correlations showed
      almost identical patterns of pelvic (S1) and thoracic (T12) movement curves in
      all anatomic planes between groups. No statistical group differences were
      detected for either pelvic or thoracic oscillation amplitudes. However, Student's
      t test showed significantly higher coefficients of variation (P < 0.01) in all
      anatomic planes of patients with chronic low back pain than in healthy control
      patients. CONCLUSIONS: The phasic patterns and angular spinal displacements of
      patients with nonspecific low back pain were shown to be within normal limits.
      However, the patients demonstrated higher degrees of stride-to-stride
      variability, representing increased fluctuations in dynamic thoracic and pelvic
      oscillations. These findings, resulting in less than optimal gait patterns, must
      be considered in the rehabilitation of patients with chronic low back pain.

PMID- 11568707
TI  - Irreducible dislocations of the cervical spine with a prolapsed disc: preliminary
      results from a treatment technique.
AB  - STUDY DESIGN: The preliminary results from a treatment technique for irreducible
      dislocations of the cervical spine with prolapsed disk are reported. OBJECTIVE:
      To report the success of a technique for grafting and instrumentation of the
      anterior cervical spine before reduction. This technique is useful in cervical
      fracture-dislocations irreducible through the anterior approach that must be
      approached first from the front because of a prolapsed disc. SUMMARY OF
      BACKGROUND DATA: In the treatment of cervical facet dislocations, a third
      anterior procedure often is necessary to accomplish the anterior instrumentation
      and fusion. The reported technique describes a method that eliminates this third
      procedure by using a cervical buttress plate. METHODS: Between August of 1996 and
      October 1998, four patients had dislocation of the cervical spine with a
      prolapsed disc that could not be reduced using the anterior approach. After
      discectomy and endplate preparation, a tricortical bone graft was harvested from
      the iliac crest, placed in the interspace, and held with a buttress plate screwed
      in two places into the superior vertebral body. The anterior wound then was
      closed. The posterior elements were exposed and the facets reduced by flexing the
      neck and posteriorly translating the superior segment. Fluoroscopy was used
      during the reduction to ensure that the graft was pulled into the interspace,
      that the screws in the buttress plate did not pull out of the superior vertebral
      body, and that the reduced graft did not impinge on the spinal cord. A posterior
      fusion was performed and the posterior wound closed. RESULTS: All the patients
      had consolidation of both anterior and posterior fusions. No cases of instrument
      failure occurred, either anteriorly or posteriorly. No cases of neurologic
      deterioration occurred, and no complications were attributable to the use of this
      technique. CONCLUSION: The reported technique was used successfully in the
      treatment of four patients with irreducible dislocations of the cervical spine.

PMID- 11568709
TI  - Distraction-flexion injury in a neurologically intact pediatric patient treated
      nonoperatively: case study.
AB  - STUDY DESIGN: A case study was conducted. OBJECTIVE: To detail the successful
      nonoperative management of a distraction-flexion Salter-Harris Type 1 midcervical
      spine injury in a young child. SUMMARY OF BACKGROUND DATA: Documented cases of
      neurologically intact pediatric patients with unstable flexion-distraction
      injuries of the midcervical spine are rare. METHODS: A case report and literature
      review are presented. RESULTS: A rare distraction-flexion injury was successfully
      treated nonoperatively. CONCLUSIONS: Although distraction-flexion cervical spine
      injuries are common in adults and often occur with concomitant neurologic
      sequelae, they also can occur in the pediatric patient. Whereas these injuries
      require surgery in adults, they can be managed nonoperatively in the pediatric
      population.

PMID- 11568710
TI  - Transoral resection and reconstruction for primary osteogenic sarcoma of the
      second cervical vertebra.
AB  - STUDY DESIGN: A case of primary osteogenic sarcoma at the second cervical
      vertebra is reported. OBJECTIVES: To document an osteogenic sarcoma of the second
      cervical vertebra and its treatment, and to review the literature. SUMMARY OF
      BACKGROUND DATA: Primary osteosarcoma of the cervical spine is encountered
      infrequently, and its location in the upper cervical spine is extremely rare. Two
      cases of osteosarcoma in the second cervical vertebra have been reported
      previously in the literature. METHODS: A 15-year-old boy with a mass lesion in
      the axis was treated surgically by anterior transoral resection, fusion, and
      reconstruction of the defect with a Harms cage. The resection was completed by
      posterior excision of the remaining vertebral elements, and by occipitocervical
      instrumentation and fusion between the occiput and the fourth cervical vertebra.
      The therapy was completed by adjuvant chemotherapy and radiotherapy. RESULTS: At
      this writing, 40 months after the initial diagnosis, the patient was in a good
      state of health with his underlying disease. CONCLUSIONS: The axis is a very rare
      location for the occurrence of primary osteosarcoma. Osteosarcoma may
      histologically mimic chondroblastoma. The axis can be surgically exposed,
      resected, and instrumented transorally. The stabilization must be augmented by
      posterior occipitocervical fusion.

PMID- 11568711
TI  - Traumatic lumbosacral dislocation: case report.
AB  - STUDY DESIGN: A case report of a bilateral lumbosacral dislocation without a
      fracture is presented. OBJECTIVE: To report the diagnosis and treatment of a
      traumatic lumbosacral dislocation. SUMMARY OF BACKGROUND DATA: Lumbosacral
      dislocations without fractures are rare injuries, with only four cases reported
      in literature. The recommended treatment consists of an anterior lumbar interbody
      fusion after posterior reduction with pedicle screw instrumentation. METHODS: The
      1-year follow-up evaluation of a 17-year-old male with a traumatic lumbosacral
      dislocation, diagnosed with computed tomography and magnetic resonance imaging,
      and treated with a posterior lumbar interbody fusion procedure combined with a
      posterolateral fusion is reported. RESULTS: At 1 year after surgery the patient
      is asymptomatic and has resumed his heavy manual work. Radiologic evidence of
      interbody fusion is present. CONCLUSIONS: Lumbosacral dislocations are rare
      injuries. The authors demonstrate the feasibility of a posterior lumbar interbody
      fusion procedure in combination with posterolateral instrumentation and fusion.

PMID- 11568713
TI  - Histology of intervertebral disc protrusion: an experimental study using an aged
      rat model.
AB  - STUDY DESIGN: In vitro experimental intervertebral disc ruptures of aged rats
      were examined histologically. OBJECTIVES: To clarify the mechanism of
      intervertebral disc herniations by microscopic investigation of ruptured discs.
      SUMMARY OF BACKGROUND DATA: Clinically, disc herniations have been classified
      into two types: extrusion and protrusion. However, the pathogenesis of protrusion
      type herniations has not yet been demonstrated by any studies. To clarify this
      issue, it is essential to establish an appropriate model producing disc
      herniations, and to examine the sequential changes in the structure of herniated
      discs. METHODS: Lumbar discs of 2-year-old rats were examined histologically and
      compared with human lumbar discs. To examine structural changes in discs
      subjected to repetitive motion stress, 400 repetitions of a sequence of flexion
      (30 degrees ) and axial rotation (6 degrees ) were applied in vitro to the lumbar
      discs of the animals. RESULTS: The microstructure of normal lumbar discs in aged
      rats was similar in many ways to the human lumbar discs in a 20- to 40-year-old
      adult. Of 10 discs subjected to repetitive stress, 4 were ruptured at the
      junction between the posterior anulus fibrosus and the sacral cartilage endplate.
      One had an extruded nucleus pulposus, and three had a protruded anulus fibrosus,
      which displayed disorganized structure containing widened and flaccid lamellae.
      CONCLUSIONS: The results from this study indicate that disc protrusion can be
      caused by disorganization of the ruptured annular lamellae, not by focal
      compression of the nucleus pulposus.

PMID- 11568715
TI  - Myelopathy induced by a thoracic intraspinal synovial cyst: case report and
      review of the literature.
AB  - STUDY DESIGN: A follow-up study of a patient with myelopathy resulting from a
      thoracic intraspinal synovial cyst was conducted. OBJECTIVE: To present this
      unusual form of myelopathy, and to highlight this unique condition by a
      literature review. SUMMARY OF BACKGROUND DATA: Intraspinal synovial cysts are
      quite common in the lumbar spine, but much rarer in the thoracic spine, where
      they may produce myelopathy from spinal cord compression. The reported patient
      presented with a lumbar degenerative spondylolisthesis, but actually was
      symptomatic from a thoracic synovial cyst. METHODS: Clinical and radiographic
      details of a patient with a thoracic intraspinal synovial cyst are presented. A
      complete literature review also summarizes previously published material on this
      topic. RESULTS: The thoracic intraspinal synovial cyst was appropriately
      identified on a magnetic resonance image examination. The patient underwent
      successful thoracic spinal cord decompression with stabilization and fusion. The
      myelopathy resolved postoperatively. CONCLUSIONS: The possibility of a thoracic
      synovial cyst should be considered in the evaluation of pain associated with
      myelopathy.

PMID- 11568714
TI  - Pathologic mechanism of experimental scoliosis in pinealectomized chickens.
AB  - STUDY DESIGN: This study was designed to investigate the pathologic mechanisms of
      idiopathic scoliosis using experimentally induced scoliosis in chickens.
      OBJECTIVE: To understand the process of producing a scoliotic deformity in
      pinealectomized chickens. SUMMARY OF BACKGROUND DATA: Pinealectomy in chickens
      consistently produces scoliosis with anatomic characteristics similar to those of
      human idiopathic scoliosis. Pinealectomized chickens are an important animal
      model for the study of idiopathic scoliosis. METHODS: In this study, 40 chickens
      were divided into two groups; 20 chickens treated with pinealectomy and 20 with a
      sham operation as control subjects on the second after hatching. The chickens in
      both groups then were killed at intervals ranging from 1 to 20 weeks after
      surgery. Their spines were examined visually and radiologically for the presence
      of a scoliotic curve and vertebral deformities. RESULTS: Rotational
      lordoscoliosis developed in pinealectomized chickens. The chickens with severe
      scoliosis were characterized by apically wedge-shaped vertebrae. In contrast, no
      scoliosis with any vertebral deformity developed in any of the chickens that
      received a sham operation. CONCLUSIONS: Because there normally is evidence of
      lordosis in the thoracic spine of chickens, the rotational instability of the
      spine induced by pinealectomy may produce a scoliotic deformity as a secondary
      phenomenon. Pinealectomy in chickens consistently produces scoliosis with
      anatomic characteristics similar to those of human idiopathic scoliosis. The
      authors believe that disturbance of the equilibrium and the posture mechanism
      associated with a defect in melatonin synthesis after pinealectomy may promote
      the development of rotational lordoscoliosis.

PMID- 11568716
TI  - Scoliosis in Proteus syndrome: case report.
AB  - STUDY DESIGN: The case of patient with scoliosis based on a rare hamartomatous,
      Proteus syndrome, is reported. OBJECTIVES: To present the characteristics of
      scoliosis associated with Proteus syndrome, and to investigate the mechanisms
      that cause it. SUMMARY OF BACKGROUND DATA: Proteus syndrome, a rare hamartomatous
      disorder first coined by Wiedemann, manifests many clinical morphologic
      abnormalities including scoliosis. The characteristics and cause of scoliosis in
      this syndrome are fully unknown. METHODS: A patient with Proteus syndrome was
      followed from the age of 3 months to the age of 21 years. This patient received
      spinal corrective surgery for severe scoliosis. Detailed investigations of the
      scoliosis as well as the physical and imaging examinations were performed to
      characterize the scoliosis. RESULTS: Computed tomography showed exclusive
      asymmetric appearance of lumbar spine, hypertrophy of the only right facet
      joints, and pedicles at L1-L4, which accorded with the right-side hemihypertrophy
      of the patient's extremities. CONCLUSIONS: Scoliosis with Proteus syndrome seems
      to be based on hemihypertrophy, with no influence of mechanical stress.

PMID- 11568717
TI  - The role of acute decompression and restoration of spinal alignment in the
      prevention of post-traumatic syringomyelia: case report and review of recent
      literature.
AB  - STUDY DESIGN: Case report. INTRODUCTION: Acute post-traumatic syringomyelia
      formation after spinal cord injury has been considered a rare complication. At
      this writing, most recent reports have surfaced in neurosurgical journals. As an
      entity, post-traumatic syringomyelia has not been widely appreciated. It has been
      confused with conditions such as Hansen's disease or ulnar nerve compression at
      the cubital tunnel. One study also demonstrated that the occurrence of syrinx is
      significantly correlated with spinal stenosis after treatment, and that an
      inadequate reduction of the spine may lead to the formation of syrinx. This
      reported case describes a patient in whom post-traumatic syringomyelia began to
      develop 3 weeks after injury, which improved neurologically after adequate
      decompression. SUMMARY OF BACKGROUND DATA: A 30-year-old man sustained a 20-foot
      fall at work. He presented with a complete spinal cord injury below T4 secondary
      to a T4 fracture dislocation. The patient underwent open reduction and internal
      fixation of T1-T8. After 3 weeks, the patient was noted to have ascending
      weakness in his bilateral upper extremities and some clawing of both hands.
      METHODS: A computed tomography myelogram demonstrated inability of contrast to
      pass through the T4-T5 region from a lumbar puncture. An incomplete reduction was
      noted. The canal showed significant stenosis. A magnetic resonance image of the
      patient's C-spine showed increased signal in the substance of the cord extending
      into the C1-C2 area. The patient returned to the operating room for T3-T5
      decompressive laminectomy and posterolateral decompression including the
      pedicles, disc, and posterior aspect of the body. Intraoperative ultrasound
      monitoring showed a good flow of cerebrospinal fluid past the injured segment.
      RESULTS: On postoperative day 1, the clawing posture of the patient's hands was
      significantly diminished, and the patient noted an immediate improvement in his
      hand and arm strength. Over the next few days, the patient's strength in the
      bilateral upper extremities increased to motor Grade 4/5 on manual testing. A
      magnetic resonance image 4 weeks after decompression showed significant
      improvement in the cord diameter and signal. CONCLUSIONS: Post-traumatic
      syringomyelia has not been reported at so early a stage after injury. This
      disorder is an important clinical entity that must be recognized to prevent
      potentially fatal or devastating complications. As evidenced by the reported
      patient and the literature, if this disorder is discovered and treated early,
      permanent deficit can be avoided. The prevention of post-traumatic syringomyelia
      requires anatomic realignment and stabilization of the spine without stenosis,
      even in the case of complete injuries, to maintain the proper dynamics of
      cerebrospinal fluid flow.

PMID- 11568718
TI  - [Sentinel lymph node for breast cancer: remove less to know more].
AB  - BACKGROUND: Our aim was to study the value of sentinel lymph node (SLN) biopsy in
      patients with breast cancer seen at a community hospital. METHODS: Consecutive
      cases receiving primary treatment for unicentric breast cancer less than 3 cm in
      diameter were prospectively studied from January 1999 to July 2000. All patients
      signed a detailed informed consent. The majority of patients (89%) underwent a
      combined technique of intradermal injection of 0.3-1.2 mCi of (99)Tc and 1-3 cc
      of Patent Blue at the biopsy site. Intraoperative localization was performed with
      a hand-held gamma probe. The first 15 patients underwent routine back-up
      lymphadenectomy. Thereafter, only patients with positive SLN, suspicious
      findings, or personal preference underwent formal axillary dissection. RESULTS:
      One hundred eight cases were included in the study with a median age of 61 years
      and a median diameter of the breast tumor of 1.5 cm. Success rate for
      identification of SLN was 94% (101/108 cases). A total of 917 additional lymph
      nodes were removed after SLN biopsy (median 6.5 lymph nodes/patient). Correlation
      between SLN and the final axillary status was 98%. In 20/36 patients (61%) with
      positive axillary status the sentinel lymph node was the only positive one. Ten
      patients had only microscopic foci of cancer found in the SLN. Sixty-seven
      patients (62%) could have avoided axillary dissection becouse the SLN was found,
      it was negative, and there were no other intraoperative suspicious findings.
      CONCLUSIONS: SLN biopsy is accurate and easily reproduced. Our data confirms that
      the majority of breast cancer patients may no longer need routine axillary
      lymphadenectomy.

PMID- 11568719
TI  - [Primary lymphoma of the gastrointestinal tract].
AB  - BACKGROUND: A retrospective analysis of 12 years' experience (1987-1999),
      concerning gastro-intestinal lymphomas (LNH-GI) has been performed, to offer a
      contribution for the identification of the diagnostic and prognostic criteria.
      METHODS: During this period, 11 cases (9 male and 2 female) have been treated: 8
      with gastric localization and 3 with intestinal localization, with age ranging
      between 12 and 78 years. Most of the analyzed cases (5 cases out of 8 with
      gastric localization and all the cases with intestinal localization) underwent
      surgical treatment without a sure understanding of the nature of lymphoma.
      Clinical observation showed forms in an advanced state of local development.
      RESULTS: However, the low specifity of available diagnostic tools and the
      therapeutic delay are factors that seems do not influence the prognosis, as well
      as the stage of the disease determined with traditional classification methods.
      The aspect that seems to be crucial for the prognosis of the disease is the
      histotype (5 low grade cases free of desease from 36 months to 10 years, vs 4
      high grade cases died between 46 days and 40 months after the surgical
      treatment). CONCLUSIONS: Some interesting considerations arise from the analysis
      of the diagnostic procedure and from the method of treatment: the specifity and
      precocity of the diagnosis could be improved by a large use of endoscopic
      ultrasonography that allow to obtain deep biopsy; the identification of histotype
      before surgical treatment can address and modulate the therapeutic strategy
      eliminating the over treatment for L.G. forms.

PMID- 11568720
TI  - The role of laparoscopic adhesiolysis in chronic abdominal pain.
AB  - BACKGROUND: Intraperitoneal adhesions seem to be a possible cause of chronic
      abdominal pain, but reports of their etiological role are controversial.
      Laparoscopic adhesiolysis has been proposed as treatment of choice, even tough
      reports of success are contradictory. The aim of our prospective study, was to
      determine whether laparoscopic adhesiolysis ameliorates chronic abdominal pain in
      patients with pathological abdominal adhesions. METHODS: Forty-five patients with
      chronic abdominal pain, lasting for more than 6 months, without abnormal findings
      other than pathological intraperitoneal adhesions found at laparoscopy, underwent
      laparoscopic adhesiolysis. RESULTS: Forty-one patients (91.1%) were available for
      follow-up after an average time interval of 18 months (range: 12-41 months): 24
      patients (58.5%) were free from abdominal pain; 10 (24.4%) reported significant
      amelioration of pain, while 7 (17.1%) patients had no amelioration. CONCLUSIONS:
      Laparoscopy is an efficient means of assessing patients with chronic abdominal
      pain, and laparoscopic adhesiolysis cures or ameliorates. Chronic abdominal pain
      in more than 80% of patients.

PMID- 11568722
TI  - [Personal experience with the endoscopic treatment of pancreatic pseudocysts.
      Long-term results and analysis of prognostic factors].
AB  - BACKGROUND: The aim of this study was to assess the safety and utility of
      endoscopic treatment of pancreatic pseudocysts. Prognostic factors for the
      outcome of endoscopic drainage were assessed in a prospective analysis. METHODS:
      Forty-nine consecutive symptomatic patients were included in the study.
      Transmural drainage was used in 30 patients and transpapillary drainage in 19
      patients. RESULTS: Successful drainage was achieved in 27/30 (90%) of patients
      after transmural drainage and in 16/19 (84.2%) patients after transpapillary
      drainage. Twelve (24.5%) patients had complications; 2 patients had bleeding, 2
      had mild pancreatitis, 8 had cyst infection, in relation to the presence of
      necrosis (5 patients) or stent clogging (3 patients). Nine patients (20.9%) had
      recurrence of pseudocyst. Endoscopic drainage was a definitive treatment in 37
      out of 49 (75.5%) patients (median follow-up: 25.9 months). Presence of necrosis
      was the only significant prognostic factor for infectious complication.
      CONCLUSIONS: Endoscopic drainage provides a successful and safe minimally
      invasive approach to the management of pancreatic pseudocysts.

PMID- 11568721
TI  - [Inguinal hernia prosthetic repair through the anterior approach].
AB  - BACKGROUND: Aim of this study is to compare the Lichtenstein's, Rutkow's and PHS
      techniques of inguinal hernia repair in terms of therapeutical efficacy and grade
      of acceptability, expressed in function of the complications, compliance and
      performance status of the patients. METHODS: The preliminary results of an
      ongoing prospective non-randomized study on the most frequently used techniques
      of inguinal hernia repair (PHS, Rutkow's, and Lichtenstein's) are reported. Sixty
      patients with primary inguinal hernia were divided into three homogeneous groups
      for age, gender, Gilbert's type of hernia, type of anesthesia, ASA class. The
      three groups underwent PHS, Rutkow's and Lichtenstein's inguinal hernia repairs,
      respectively. The end-points of the study were: operative time, intra- and
      postoperative pain, intra- and postoperative complications, patients compliance
      and performance status. RESULTS: The mean operative time were 40', 41' and 36'
      minutes for the PHS, Rutkow's and Lichtenstein's procedures, respectively. One of
      patients of the PHS group, five of the Rutkow's and none of those undergoing
      Lichtenstein's repair needed mild intraoperative sedation. Mild postoperative
      pain was recorded in 5% of the patients undergoing PHS repair and 10% undergoing
      Rutkow's repair. No intraoperative complications, difference in compliance and
      performance status were detected in the three groups. CONCLUSIONS: The conclusion
      is drawn that the PHS, Rutkow's and Lichtenstein's procedures for inguinal hernia
      repair are safe (no complications), effective and well accepted by the patients
      (85% of the patients expressed a very good judgement) although the Rutkow's
      repair seems more invasive. The appearance of a better trend, in patient's
      compliance and performance status when operated with the PHS technique, need to
      be confirmed in the future but, if it will be, this could became our first choice
      technique of repair for the medium and large hernia defect.

PMID- 11568723
TI  - [Recent concepts regarding the treatment of traumatic hemopneumothorax].
AB  - BACKGROUND: The aim of the study was to examine the different therapeutic options
      for traumatic hemopneumothorax and in particular the latest concepts
      (videothoracoscopy). METHODS: A retrospective study was performed on a group of
      20 patients with post-traumatic hemothorax and/or pneumothorax attending the
      emergency department at Ospedale Vittorio Emanuele in Catania over the past 10
      years where 2500 patients with abdominal and/or thoracic trauma were treated
      during the same period. The patients included 18 males and 2 females with a mean
      age of 35 years (range 13-70). The cause of injury was a gunshot wound in 8
      patients, a blunt trauma following a road accident in 9 and a stab wound in 3
      patients. A drainage tube was inserted in 15 patients (a videothoracoscopic
      approach was used in 2 cases); 3 patients required a diaphragmatic suture and 2
      thoracotomy (inferior lobectomy and repair of the main left bronchus). RESULTS:
      Three out of 20 patients died with an overall mortality rate of 15%. Two patients
      died respectively from severe brain and abdominal injuries associated with
      thoracic trauma, while the third patient died from septic complications.
      CONCLUSIONS: In the past few years videothoracoscopy has allowed a different
      approach to be used in patients affected by hemo-pneumothorax since it allows a
      more accurate diagnosis (extent and origin of bleeding, identification of
      associated diaphragmatic lesion) and the possibility of treating pleuro-pulmonary
      injuries without performing extensive thoracotomies.

PMID- 11568724
TI  - [Long-term evaluation of the endoscopic treatment of gastric polyps].
AB  - BACKGROUND: The authors intend to evaluate the long-term efficacy of endoscopic
      treatment of gastric polyps. METHODS: They report their experience in 5000 upper
      gastro intestinal endoscopies performed between 1985 and 1998. The method used
      aimed to evaluate the distribution of polyps by sex and age, the frequency of
      various histological types and the incidence of complications in relation to
      histological type and the size of the polyps. The authors also analysed the
      indications and criteria of choice between endoscopic treatment and surgery and
      they calculated the incidence of malignant neoplasm and complications in relation
      to the endoscopic method used, as well as the incidence of relapse at the medium
      and long-term follow-up. They searched for the presence of neoplasms in the
      follow-up and compared their personal experience with data from international
      literature. RESULTS: The results obtained show that non-surgical treatment of
      gastric polyps is resolutive in most cases. The endoscopic resection of polyps
      was performed using a polypectomy loop. In patients converted to surgery, the
      necessity for the operation was caused by an unexpected hemorrhage that could not
      be controlled using endoscopic treatment. In this case, the operation consisted
      of resecting the entire wall of the lesion, including an extemporary histological
      analysis. CONCLUSIONS: The authors' experience allows them to state that
      endoscopic treatment of this gastric pathology is efficacious and free from risks
      and complications if stringent patient selection criteria are used (dimensions,
      morphological characteristics of the lesion) and control procedures over time
      suited to the potential malignancy of each histological type are carried out.

PMID- 11568725
TI  - [Indications for the surgical treatment of abdominal aortic aneurysms].
AB  - BACKGROUND: On the basis of a literature review and of personal experience, the
      authors analyze the main indications and the best strategy for elective surgical
      repair of infrarenal abdominal aortic aneurysm (AAA). METHODS: Personal
      experience concerning elective surgical treatment of 110 patients with infrarenal
      AAA, is presented. RESULTS: No operative deaths have been observed and the
      postoperative recovery was regular in 108 patients. Two early complications
      (colon ischemia) and ten late postoperative complications (5 pseudoaneurysms, 5
      sexual dysfunctions) occurred. CONCLUSIONS: The main therapeutic guidelines
      concerning the management of AAA should follow specific indications (aneurysm
      dimensions and growth rates). Indications for operative repair of aneurysms
      obviously should be judged in relation to the presence or absence of associated
      risk factors or concomitant medical conditions. In most cases, aneurysm repair
      can be performed safely, despite associated medical risks, by careful
      preoperative evaluation and preparation.

PMID- 11568726
TI  - [Acute cholecystitis in patients over 70 years old].
AB  - BACKGROUND: Gallstone disease is the most common surgical indication in the
      elderly. Post-operative prognosis is severe in elderly with acute cholecystitis.
      Aim of this paper is to investigate the factors responsible for the severe
      prognosis and to detect how it could be improved. METHODS: One hundred fifty
      seven patients, aged between 70 and 85 years (average 82 years), undergoing
      cholecystectomy between the years 1990 and 2000 have been studied; 65 patients
      (group A) had acute cholecystitis; 92 (group B) had uncomplicated gallbladder
      stones. RESULTS: Acute cholecystitis was the first symptom of gallstone disease
      in 69.2%. Laparocholecystectomy was performed in 31 cases (47.6%) of group A and
      in 58 cases (63.7%) of group B. In those cases with acute cholecystitis the
      postoperative morbidity (18.4%) was higher than in group B (1.0%), (A vs B:
      chi(2)=15.3; p<0.001). Similarly, postoperative mortality was higher (6.1% vs
      1.0%; chi(2)=3.2; p<0.05) The severe postoperative prognosis was correlated
      significantly to index ASA (ASA II vs IV: chi(2)=7.0; p<0.001) but not to the
      technique adopted for cholecystectomy (VLC vs open: (chi)2=0.01; p=n.s.). The
      results obtained seem to confirm that the high incidence of postoperative
      complications in acute cholecystitis is due to the presence of associated
      diseases in elderly patients accompanied by the septic state. CONCLUSIONS: Early
      colecystectomy, in those cases with symptomatic, uncomplicated gallstone disease,
      might avoid severe postoperative prognosis in the elderly.

PMID- 11568727
TI  - [Polyps (single or multiple) and juvenile polyposis].
AB  - The authors underline the important aspects of juvenile familial polyposis (JFP),
      a disease transmitted as an autosomal dominant trait. A case of JFP characterized
      by the presence of hundreds of polyps in the colo-rectal intestinal tract, is
      analyzed. The single juvenile polyp, multiple polyps (=/>5 polyps) and the
      sporadic form are examined. These are mucous hamartomas which can undergo
      neoplastic transformation (in carcinoma in 68% of untreated cases), a behaviour
      similar to that of adenomatous polyps. They differ from the later due to the
      following features: epidemiology (earlier appearance age), anatomopathology
      (stroma), clinical observation (self-recovery in some cases) and genetics
      (10q23.3-18q21, genetic mutations in a locus different those of adenomatous
      polyps). It is also necessary to determine its extension by means of colonoscopy,
      ileoscopy, gastroscopy and small bowel barium enema. Patients' screening through
      construction of the genealogical family tree is fundamental. Isolation of
      possible degenerative aspects of the polyps through biopsy is also fundamental.
      Single or multiple polyps are treated endoscopically, the juvenile polyposis is
      treated surgically (colectomy, total colectomy). A rigorous follow-up of the
      patients and their family members is recommended.

PMID- 11568728
TI  - [The thyroidectomized follow-up].
AB  - Thyroid neoplasties are largely benign, and only 1% of all over malignant
      neoplasties with clinical diagnosis regard the thyroid. The histologic
      characteristics of the thyroid neoplasties assume fundamental importance both in
      diagnosis and in therapy. The authors underline the importance of the surgical
      treatment of malignant neoplasties of the thyroid with the problems connected to
      the choice of the entity of the demolition of the organ and the post-operative
      thyrohyoid residue and the importance of the correct follow-up for few patients,
      consenting to optmize the available resources.

PMID- 11568729
TI  - [Current developments in the treatment of acute generalised peritonitis].
AB  - Generalised acute peritonitis is a relatively frequently pathology which has
      always been extremely difficult to treat owing to the large number of
      complications. Considerable progress has been made over the past few years in the
      surgical treatment of these pathologies following the introduction of new
      materials accompanied by new techniques: continuous peritoneal lavage (CPL) and
      laparostomy are the best known. These techniques must be used in carefully
      selected patients. They allow a marked improvement in results: fewer cases of
      redo surgery; fewer local and general complications; shorter hospitalisation
      stay; fewer deaths. These results are possible because these techniques ensure a
      better cleansing of the peritoneal cavity, with easier removal of necrotic and
      purulent materials, the main cause of local and general complications.

PMID- 11568730
TI  - Biliary tract papillomatosis.
AB  - Papillomatosis of the biliary tract is characterised by multicentric papillary
      lesions of intra and extrahepatic biliary epithelium. It's a rare benign neoplasm
      of the biliary tract that causes obstructive jaundice with a high rate of
      malignant transformation. We described a case of papillomatosis of the biliary
      tract in a woman of 75-years-old, who came to our observation with jaundice,
      pruritus and fever. The surgical treatment consisted of cholecystectomy,
      choledochotomy and positioning a definitive T-Tube. We described our experience
      and the evolution of this disease.

PMID- 11568731
TI  - [Adrenal synchronous metastasis from non small cell lung carcinoma (NSCLC):
      combined surgical treatment? Case report and review of the literature].
AB  - The adrenal gland is a frequent site for metastases from non small cell lung
      carcinoma (NSCLC). Surgical strategy in patients with operable NSCLC with adrenal
      synchronous metastases is yet unclear. On the basis of a literature survey and of
      a personal case report, the authors analyze the main indications and the best
      strategy for solitary synchronous metastases in the adrenal gland from NSCLC.

PMID- 11568732
TI  - [Video-assisted appendectomy].
AB  - BACKGROUND: The acceptability of the classic laparoscopic technique in the
      treatment of acute appendicitis is slow, probably due to the higher costs of this
      method compared to the cheaper, efficacious, safe and rapid discharge associated
      with traditional surgery. METHODS: In order to combine the advantages of the
      laparoscopic technique with those of traditional surgery, we performed a
      retrospective study of the safety, efficacy, rapid discharge with return to
      normal working activities, and the costs in 70 patients referred to our attention
      with a diagnosis of acute appendicitis and who underwent one trocar appendectomy.
      This technique consists of positioning a single trocar in an umbilical site and
      using a 10 mm telecamera with a 5 mm operating canal. Having visualised the
      appendix and freed it from any synechiae, the distal end is grasped and it is
      removed through the umbilical trocar. Appendectomy is performed outside using a
      technique that is similar to traditional surgery. The diagnosis of acute
      appendicitis was made on the basis of clinical data (pain, leucocytosis, fever,
      possible resistance in the right iliac fossa).

PMID- 11568733
TI  - [Computer-aided preoperative planning of tissue expansion].
AB  - OBJECT: The aim of this paper is to introduce a computer program developed to
      provide objective and quantitative data useful to provide proper expander
      selection when a rectangular tissue expander has to be used. METHODS: The program
      has been developed to calculate the volume of a rectangular tissue expander to
      obtain the exact amount of yield necessary to allow for reconstruction of a
      determined defect. The only data to be supplied are the length and the width of
      the defect to be reconstructed. RESULTS: The accuracy of the results obtained by
      the computer program was tested clinically comparing preoperative data with
      volume measurements obtained at the end of the expansion procedure. In our study
      the resulting data did not show any statistically significant difference (p<0,05)
      between the two groups. CONCLUSIONS: In our opinion, although its use is not
      aimed at replacing clinical judgment based on experience and careful observation,
      this program may be considered a simple and useful adjunct for the inexperienced
      surgeon (or the occasional operator) planning to use a rectangular tissue
      expander.

PMID- 11568734
TI  - Diagnosis and management of carotid artery disease: the role of carotid artery
      stenting.

PMID- 11568735
TI  - Part I. Laparoscopic surgery for colon and rectal cancer.

PMID- 11568736
TI  - Part II. Laparoscopic approach to abdominal malignancies.

PMID- 11568737
TI  - Treatment of psoriasis. Part 1. Topical therapy and phototherapy.
AB  - New developments in the topical therapy and phototherapy of psoriasis have
      greatly improved our ability to safely and effectively treat this debilitating
      disease. Topical corticosteroids remain the most commonly prescribed agents for
      psoriasis, but they are frequently prescribed with other agents. Investigations
      of corticosteroids claiming an improved benefit/risk ratio have yielded promising
      results, but more work is needed. Use of anthralin and tar has declined with the
      availability of the noncorticosteroids calcipotriene and tazarotene. Other
      experimental topical therapies are in various stages of development. Broadband
      ultraviolet B (UVB) remains the most commonly used phototherapy light source, but
      many patients are being treated with a new form of ultraviolet light, narrowband
      UVB. Although PUVA remains one of the most effective psoriasis treatments, its
      use is declining because of its association with cutaneous malignancies. New
      radiation sources such as lasers have been added to our armamentarium of
      available therapies and even newer light source-based treatments are being
      examined. LEARNING OBJECTIVE: At the conclusion of this learning activity,
      participants should be familiar with the varying topical treatments for psoriasis
      as well as the different modalities of phototherapy. Participants should also
      have a better understanding of side effects associated with each treatment, which
      should help in determining options for therapy.

PMID- 11568738
TI  - High-dose versus medium-dose UVA1 phototherapy for patients with severe
      generalized atopic dermatitis.
AB  - BACKGROUND: Several studies have demonstrated the efficacy of UVA1 (340-400 nm)
      phototherapy for patients with severe atopic dermatitis. However, the optimum
      treatment dose has yet to be determined. Although in seminal investigations high
      UVA1 doses were used, comparable results were reported in recent studies with a
      medium-dose regimen. OBJECTIVE: Our purpose was to compare the efficacy of high
      dose with medium-dose UVA1 phototherapy for patients with severe generalized
      atopic dermatitis. METHODS: Ten adult patients with a median baseline SCORAD
      score of 67 were enrolled in an investigator-blinded, bilateral comparison study.
      Treatment was given 5 times weekly over a period of 3 weeks on an outpatient
      basis. Irradiation was performed by exposing one half of the patient's body to
      high-dose UVA1 (< or =130 J/cm(2)), and the contralateral body side received only
      half that dose. The clinical response was assessed after 5, 10, and 15
      treatments. After completion of the study, patients were followed up for 6 months
      to evaluate the duration of clinical improvement. RESULTS: All but one patient
      responded favorably to treatment. High-dose UVA1 led to a decrease of the median
      SCORAD score by 33.4% after 1 week, 38.4% after 2 weeks, and 34.7% after 3 weeks.
      The respective values for the medium-dose regimen were 29.7%, 36.4%, and 28.2%.
      The difference in efficacy between the two dosages remained below the level of
      significance at all time points. Relapses occurred after a median of 4 weeks.
      Time of onset and severity of relapse were the same for both doses. CONCLUSION:
      Our data support previous uncontrolled observations that medium-dose UVA1 is
      comparably as effective as high-dose treatment for patients with severe
      generalized atopic dermatitis. Irrespective of the dose regimen, follow-up
      examinations revealed early relapse in the majority of patients.

PMID- 11568739
TI  - Quantification of the efficacy of botulinum toxin type A by digital image
      analysis.
AB  - BACKGROUND: Botulinum toxin type A (BT-A) is increasingly being used by
      dermatologists for correction of frown lines. Because objective measurements of
      clinical results appear to be difficult, several different treatment protocols
      have been issued purely empirically or on the basis of subjective ratings.
      OBJECTIVE: Our purpose was to establish objective parameters to measure the
      efficacy of BT-A for correction of hyperkinetic facial lines. METHODS: Thirty
      consecutive patients received BT-A injections for correction of facial expression
      lines. For each patient a full range of facial expressions was recorded by means
      of a digital imaging system that allowed identical positioning and illumination
      before and after treatment. Computer-assisted measurements of brow mobility were
      used to measure muscular paralysis. RESULTS: Reproducibility of serial
      photographs by means of a digital overlay technique was confirmed by 4
      independent observers. Upward mobility of brows was decreased to 35% at 2 weeks
      and 71% at 12 weeks after treatment. In contrast, inward mobility (frowning) was
      decreased to 7% at 2 weeks and 57% at 12 weeks. Brow-to-brow distance in repose
      increased with treatment by 13% and displayed a negative correlation with age.
      CONCLUSION: The effects of BT-A on upper face muscular activity can reproducibly
      be measured by digital image analysis; this is a valuable tool for clinical
      documentation and evaluation of treatment efficacy. Onset and offset of the
      effects of BT-A display a longer time course than previously assumed. Tissue
      qualities such as elasticity contribute measurably to smoothing facial expression
      lines after BT-A treatment and correlate inversely with age.

PMID- 11568740
TI  - An analysis of reports of depression and suicide in patients treated with
      isotretinoin.
AB  - BACKGROUND: The Food and Drug Administration (FDA) has received reports of
      depression and suicide in patients treated with isotretinoin. OBJECTIVE: Our
      purpose was to provide the number and describe the cases of depression and
      suicide reported to the FDA in US patients treated with isotretinoin and to
      consider the nature of a possible association between isotretinoin and
      depression. METHODS: An analysis was made of reports of depression, suicidal
      ideation, suicide attempt, and suicide in US isotretinoin users voluntarily
      submitted to the manufacturer and the FDA from 1982 to May 2000 and entered in
      the FDA's Adverse Event Reporting System database. RESULTS: From marketing of
      isotretinoin in 1982 to May 2000, the FDA received reports of 37 US patients
      treated with isotretinoin who committed suicide; 110 who were hospitalized for
      depression, suicidal ideation, or suicide attempt; and 284 with nonhospitalized
      depression, for a total of 431 patients. Factors suggesting a possible
      association between isotretinoin and depression include a temporal association
      between use of the drug and depression, positive dechallenges (often with
      psychiatric treatment), positive rechallenges, and possible biologic
      plausibility. Compared with all drugs in the FDA's Adverse Event Reporting System
      database to June 2000, isotretinoin ranked within the top 10 for number of
      reports of depression and suicide attempt. CONCLUSION: The FDA has received
      reports of depression, suicidal ideation, suicide attempt, and suicide in
      patients treated with isotretinoin. Additional studies are needed to determine
      whether isotretinoin causes depression and to identify susceptible persons. In
      the meantime, physicians are advised to inform patients prescribed isotretinoin
      (and parents, if appropriate) of the possibility of development or worsening of
      depression. They should advise patients (and parents) to immediately report mood
      swings and symptoms suggestive of depression such as sadness, crying, loss of
      appetite, unusual fatigue, withdrawal, and inability to concentrate so that
      patients can be promptly evaluated for appropriate treatment, including
      consideration of drug discontinuation and referral for psychiatric care.

PMID- 11568741
TI  - Breast-feeding and the onset of atopic dermatitis in childhood: a systematic
      review and meta-analysis of prospective studies.
AB  - BACKGROUND: Despite the numerous studies on the possible protective effect of
      breast-feeding against the onset of atopic dermatitis during childhood, this
      issue remains controversial. OBJECTIVE: We conducted a systematic review with
      meta-analysis of prospective studies that evaluated the association between
      exclusive breast-feeding during the first 3 months after birth and atopic
      dermatitis. METHODS: A comprehensive search of the 1966-2000 MEDLINE database and
      review of the reference lists of relevant articles identified 18 prospective
      studies that met the predefined inclusion criteria. By means of a standardized
      approach, 2 of the investigators independently assessed the methodologic quality
      of the studies, duration and exclusivity of breast-feeding, outcome measures, and
      control for potential confounding factors. The same approach was applied during
      data abstraction and evaluation of the estimates of association. Summary measures
      of association were then calculated. RESULTS: The summary odds ratio (OR) for the
      protective effect of breast-feeding in the studies analyzed was 0.68 (95%
      confidence interval [CI], 0.52-0.88). This effect estimate was higher in the
      group of studies wherein children with a family history of atopy were
      investigated separately (OR = 0.58; CI, 0.41-0.92) than in those of combined
      populations (OR = 0.84; CI, 0.59-1.19). A small subset of studies of children
      without a history of atopy in first-degree relatives showed no association
      between breast-feeding and the onset of atopic dermatitis (OR = 1.43; CI, 0.72
      2.86). CONCLUSION: Exclusive breast-feeding during the first 3 months of life is
      associated with lower incidence rates of atopic dermatitis during childhood in
      children with a family history of atopy. This effect is lessened in the general
      population and negligible in children without first-order atopic relatives.
      Breast-feeding should be strongly recommended to mothers of infants with a family
      history of atopy, as a possible means of preventing atopic eczema.

PMID- 11568742
TI  - Trends in the incidence of nonmelanoma skin cancers in southeastern Arizona, 1985
      1996.
AB  - This report describes trends in the incidence of various nonmelanoma skin cancers
      in a region of high ultraviolet exposure. The Southeastern Arizona Skin Cancer
      Registry routinely identified cases of skin cancer between 1985 and 1996 through
      pathology logs and reports from dermatology offices and laboratories in 3 Arizona
      counties. The incidence rates for squamous cell carcinoma (SCC) and basal cell
      carcinoma (BCC) for non-Hispanic whites were 3 to 6 times higher than the
      incidence rates from more northern regions. The rates for non-Hispanic whites
      were approximately 11 times greater than rates for Hispanics. Furthermore, there
      was no constant increase in the incidence of nonmelanoma skin cancers. The
      incidence of SCC, in particular, demonstrated a plateau or even a modest decline
      between 1985 and 1996. Thus the incidence rates of both SCC and BCC in Arizona,
      although among the highest in the world, do not appear to be increasing as
      rapidly as predicted elsewhere.

PMID- 11568744
TI  - Degradation and migration of facial foundations.
AB  - The surface characteristics of a facial foundation on the skin affect not only
      photoprotection, but also aesthetic appearance. A 400x video microscope was used
      to study the movement of facial foundation on the face of 12 female subjects with
      oily, dry, and normal skin in a controlled environment over 8 hours. This
      evaluation revealed gradual degradation of the cosmetic film and accumulation of
      facial foundation pigment particles in the follicular ostia. This cosmetic
      migration decreases photoprotection and may explain the perifollicular nature of
      some cutaneous reactions to facial foundations.

PMID- 11568743
TI  - Gram-negative bacterial toe web infection: a survey of 123 cases from the
      district of Cagliari, Italy.
AB  - BACKGROUND: Foot intertrigo is mostly caused by dermatophytes and yeasts, less
      frequently by gram-positive and gram-negative bacteria. Nevertheless, the
      importance of polymicrobial infections and especially colonizations of
      Pseudomonas aeruginosa can cause therapy problems in relation to antibiotic
      resistance and the risk of potentially lethal complications. OBJECTIVE: The aim
      of this study was to evaluate the main epidemiologic and clinical features of
      intertrigo from gram-negative bacteria, the function of promoting factors, and
      the measures taken to treat and prevent this disorder. METHODS: Between 1989 and
      1998, 123 cases of intertrigo from gram-negative bacteria were observed at the
      Cagliari University Dermatology Department. Routine clinical and blood
      examinations, repeated bacterioscopic and mycologic examinations, cultures aimed
      at identifying the responsible bacteria, and antibiograms were performed.
      RESULTS: P aeruginosa was found to be the prevailing pathogen, both alone and
      associated with other gram-negative bacteria (such as Escherichia coli, Proteus
      mirabilis, Morganella morganii) and gram-positive bacteria. Clinical
      manifestations were similar in the majority of patients: erythema,
      vesicopustules, erosions, and marked maceration caused by abundant, malodorous
      exudate. Lesions affected the interdigital spaces of both feet and frequently
      extended to the planta and the back of the toes. Patients complained of burning
      and pain. Successful therapies were achieved with combined topical and systemic
      treatment; to avoid the risk of antimicrobial resistance, the choice of the
      active antibiotic was guided by antibiograms. CONCLUSION: In all symptomatic toe
      web infections, the presence of gram-negative germs, such as P aeruginosa, should
      be investigated to avoid the risk of treatment failures and more severe local or
      systemic complications.

PMID- 11568745
TI  - Consensus conference: acitretin in combination with UVB or PUVA in the treatment
      of psoriasis.
AB  - Although adjunctive treatment with retinoids in concert with either psoralen
      ultraviolet A (PUVA) or ultraviolet B (UVB) phototherapy has been a treatment
      option for chronic, moderate to severe plaque psoriasis for nearly two decades,
      acitretin-UV therapy is an underutilized therapeutic modality. According to a
      recent member survey by the National Psoriasis Foundation, many psoriasis
      patients are frustrated with available treatment options, which they perceive as
      ineffective, inconvenient, and/or excessively conservative. Treatment of
      psoriasis with acitretin in concert with UVB or PUVA is emerging as a viable
      clinical strategy. Compared with either acitretin or UV light monotherapy alone,
      the combination regimen enhances efficacy and limits treatment frequency,
      duration, and cumulative doses. These effects translate into care that is more
      effective, better tolerated, more convenient, less costly, and, perhaps, safer
      during long-term treatment than phototherapy alone. Drawing from an extensive
      literature search and the expertise of its participants, this consensus
      conference advances clinical recommendations as well as "clinical pearls" for
      health providers who treat patients with chronic, moderate to severe plaque
      psoriasis and suggests avenues for future research.

PMID- 11568746
TI  - Treatment of recurrent auricle pseudocyst with intralesional injection of
      minocycline: a report of two cases.
AB  - Pseudocyst of the auricle (PCA) is characterized by asymptomatic and fluctuant
      swelling of the external ear and frequent relapses despite various therapeutic
      approaches. We describe two patients with recurrent PCA who were successfully
      treated with intralesional injection of 1 mg/mL of minocycline hydrochloride
      (minocycline), 2 or 3 times at 2-week intervals. Intralesional injection of
      minocycline may be a new therapeutic choice for conservative management of PCA,
      especially in recurrent cases. The mechanisms of minocycline action that may have
      led to reduction of the cystic lesions are discussed.

PMID- 11568747
TI  - Energy density and numbers of treatment affect response of keloidal and
      hypertrophic sternotomy scars to the 585-nm flashlamp-pumped pulsed-dye laser.
AB  - BACKGROUND: The 585-nm flashlamp-pumped pulsed-dye laser (PDL) has proven to be
      the treatment of choice for certain keloids and hypertrophic scars, but the
      precise fluence, numbers of treatment, and treatment interval remain anecdotal.
      OBJECTIVE: This study was performed to determine whether the therapeutic outcome
      of the PDL varies with the energy density (fluence) of the laser pulses and
      numbers of treatment. METHOD: Ten previously untreated, erythematous, keloidal or
      hypertrophic median sternotomy scars of 10 patients were divided into 4 segments
      and were randomly treated with a 585-nm PDL at a fluence of 3, 5, and 7 J/cm(2)
      to 3 of 4 segments every 4 weeks for a total of 6 treatment sessions. One segment
      of each patient's scars was untreated and served as a control. Clinical
      improvement including scar height, erythema, and pliability was evaluated before
      treatment and every 8 weeks for a total period of 32 weeks. Self-assessment was
      also determined by patients on a 25% increment of improvement scale comparing
      week 0 and week 32. RESULTS: A significant improvement in scar height, erythema,
      and pliability was noted in all laser-treated scar areas. There was no
      significant difference in treatment outcome versus the fluence of the laser (3,
      5, and 7 J/cm(2)), although there was a trend for lower fluences to show more
      improvement. Objective clinical improvement was seen as early as week 16, after
      more than two treatments were given. Multiple treatments (>2) appeared to provide
      a greater percentage of scar resolution. CONCLUSIONS: The clinical improvement of
      scars after PDL treatment demonstrates no statistically significant fluence
      dependence in this study, but a trend toward better response with lower fluences
      is seen. In addition, multiple treatment sessions are suggested for achieving
      greater response.

PMID- 11568748
TI  - Treatment of a cafe-au-lait macule with the erbium:YAG laser.
AB  - The erbium:YAG laser is a relatively new instrument for skin rejuvenation. We
      present a case of a "Q-switched laser-resistant" cafe-au-lait macule that was
      successfully treated with the erbium:YAG laser.

PMID- 11568749
TI  - Hypersensitivity to mosquito bites as the primary clinical manifestation of a
      juvenile type of Epstein-Barr virus-associated natural killer cell
      leukemia/lymphoma.
AB  - Hypersensitivity to mosquito bites or mosquito allergy is a mysterious disorder
      that has been reported mainly in Japanese patients (at least 58 patients) in the
      first two decades of life. The skin lesion at bite sites is typically a bulla
      that develops into necrosis. Patients simultaneously exhibit a high temperature
      and general malaise and subsequently may experience lymphadenopathy and
      hepatosplenomegaly. Recent studies have revealed that this mosquito
      hypersensitivity is associated with chronic Epstein-Barr virus infection and
      natural killer cell leukemia/lymphoma. The natural killer cell, infected with
      monoclonal (or oligoclonal) Epstein-Barr virus, seems to be involved in the
      pathogenesis of the hypersensitivity. Half of the patients reported died of
      hemophagocytic syndrome (or malignant histiocytosis), granular lymphocyte
      proliferative disorder, or lymphomas. We propose that this disease, defined as
      the triad of hypersensitivity to mosquito bites, chronic Epstein-Barr virus
      infection, and natural killer cell leukemia/lymphoma, is a clinical entity mostly
      seen in Asians.

PMID- 11568750
TI  - Guidelines of care for primary cutaneous melanoma.

PMID- 11568751
TI  - Surgical pearl: use of nerve blocks for botulinum toxin treatment of palmar
      plantar hyperhidrosis.

PMID- 11568752
TI  - Sweet's syndrome in acute myelogenous leukemia presenting as periorbital
      cellulitis with an infiltrate of leukemic cells.
AB  - Sweet's syndrome is characterized by the abrupt onset of fever, neutrophilic
      leukocytosis, and erythematous, tender pseudovesiculated plaques or nodules that
      respond readily to corticosteroid therapy. It is usually distinguished by the
      presence of mature neutrophils on histopathologic examination. We describe a 38
      year-old man with acute myelogenous leukemia who had an erythematous vesicular
      eruption of the left eye develop that resembled cellulitis. A biopsy specimen
      revealed a dermal infiltrate of mature neutrophils and immature myeloblastic
      precursors. He later had hemorrhagic pseudovesiculated plaques develop
      bilaterally on his hands. A biopsy specimen again revealed abundant neutrophils
      with immature forms. A similar eruption developed at the site of a Hickman
      catheter placement 4 months later. His skin lesions responded rapidly to oral
      corticosteroids. This case is unique in that his initial presentation of Sweet's
      syndrome resembled orbital cellulitis that was characterized by immature myeloid
      precursors on histopathology.

PMID- 11568753
TI  - Rheumatoid neutrophilic dermatitis in a woman with seronegative rheumatoid
      arthritis.
AB  - Rheumatoid neutrophilic dermatitis (RND) is an unusual cutaneous reaction in
      patients with rheumatoid arthritis (RA). RND is characterized by symmetric,
      erythematous papules, plaques, nodules, and urticarial lesions often located over
      the joints, extensor surfaces of the extremities, or the trunk. This entity
      demonstrates an intense neutrophilic dermal infiltrate without vasculitis. All
      patients previously reported with RND had severe RA with relatively high titers
      of rheumatoid factor when tested. A 67-year-old woman had a 2-month history of
      multiple, tender, 4 to 8 mm erythematous, crusted papules and nodules that
      occurred in clusters on her anterior thighs, knees, and legs. She suffered from
      severe disabling seronegative RA. RND may complicate seronegative RA.

PMID- 11568754
TI  - A unique case of a benign disseminated angioproliferation combining features of
      Kaposi's sarcoma and diffuse dermal angioendotheliomatosis.
AB  - A female patient undergoing chronic hemodialysis had disseminated, violaceous,
      and partly ulcerated plaques develop on the trunk. Lesions had erupted
      simultaneously over a period of 4 weeks and resolved within 5 months after
      steroid treatment. By histopathology, the papillary dermis was densely filled
      with blood vessels lined by a single layer of differentiated endothelial cells, a
      growth pattern resembling diffuse dermal angioendotheliomatosis. In some areas,
      endothelial cells were spindle shaped and formed discontinuous lumina. Red blood
      cells were interspersed within these slits, giving the lesions a kaposiform
      appearance. By immunohistochemistry, endothelial cells reacted with the
      antibodies anti-von Willebrand factor, anti-CD31, and anti-CD34 and with the
      lectin Ulex europaeus-1. The course of the disease combined with the unusual
      histopathology makes this case a unique form of a benign disseminated kaposiform
      angioproliferation.

PMID- 11568756
TI  - Acquired dermal melanocytosis: appearance during pregnancy.
AB  - We report the first case of acquired dermal melanocytosis (ADM) appearing during
      pregnancy. A 23-year-old Hispanic woman presented to the Dermatology Clinic of
      Columbia-Presbyterian Medical Center during the second trimester of pregnancy
      with a nonpalpable blue-gray patch with interspersed discrete brown macules on
      the right lower extremity. It had appeared during the first trimester of
      pregnancy. Cutaneous biopsy specimens revealed dermal melanocytes. A review of
      all reported cases of this rare dermatosis in the international literature is
      presented.

PMID- 11568755
TI  - Lichen myxedematosus with systemic involvement: clinical and autopsy findings.
AB  - Lichen myxedematosus is a rare disease that is characterized by the formation of
      lichenoid papules and plaques. Histologic examination shows deposition of
      mucinous material in the dermis. We report the case of a patient with cutaneous
      and systemic involvement and examine the clinical and postmortem data.

PMID- 11568757
TI  - Lichen planus occurring after hepatitis B vaccination: a new case.
AB  - Lichen planus is a pruritic inflammatory dermatosis of unknown origin. An
      increased prevalence of a wide range of liver disease in lichen planus has been
      observed by many authors. Most recently, many reports appeared of the occurrence
      of lichen planus after administration of different types of hepatitis B vaccines.
      We report one case and briefly review this intriguing observation.

PMID- 11568758
TI  - Lichenoid drug eruption to salsalate.
AB  - Cutaneous lichenoid eruptions can arise as a result of exogenous compound
      exposures. Pharmaceutical drugs, industrial compounds, and inhaled particles have
      been implicated as causative agents. To date, there have been no recorded cases
      of lichenoid drug eruptions (LDEs) caused by clinical use of the nonsteroidal
      anti-inflammatory drug salsalate. We describe a patient who experienced a
      lichenoid eruption after the initiation of salsalate for relief of arthritic
      pain. This eruption emerged after 1 month of therapy with salsalate, persisted
      for as long as salsalate was administered, and cleared within 3 weeks of
      discontinuing the medication. LDEs can clinically and histologically resemble
      idiopathic or classic lichen planus. Integrating drug history, clinical
      morphology, clinical distribution, and histopathology can aid in the
      differentiation. As in our patient's case, curative treatment for LDE requires
      discontinuation of the drug.

PMID- 11568759
TI  - Disseminated cutaneous infection with Mycobacterium kansasii: genotyping versus
      phenotyping.
AB  - Mycobacterium kansasii is a common and virulent pathogen. However, primary
      cutaneous M kansasii infection has rarely been reported, totaling to only 34
      cases since 1965. This low incidence has not been explained, but probably is due
      to difficulty in culture or phenotyping. We describe the first reported case of
      cutaneous M kansasii diagnosed by genotyping, which is based on the DNA extracted
      from the formalin-fixed and paraffin-embedded tissue.

PMID- 11568760
TI  - Newly described weathering pattern in pili annulati hair shafts: a scanning
      electron microscopic study.
AB  - Certain scalp hair shafts from 2 of 10 cases of pili annulati examined by
      scanning electron microscopy exhibited an unusual weathering pattern. The
      majority of affected hair shafts showed minor surface abnormalities at regular
      intervals (nodes) associated with the underlying spaces. However, in a few
      examples, there was marked damage to the cuticle at the nodes exposing the
      underlying cortex; in severe cases there was cracking of both cuticle and cortex.
      These damaged nodes were also associated with trichorrhexis nodosa-like breaks of
      the hair shaft. This study shows that the nodes in pili annulati may have some
      inherent weakness that could result in breaks in the hair shaft exposed to
      physical trauma.

PMID- 11568761
TI  - Keratosis pilaris and hereditary koilonychia without monilethrix.
AB  - Keratosis pilaris is found commonly in isolation as well as associated with other
      conditions. We describe a family with keratosis pilaris and hereditary
      koilonychia, with an autosomal dominant pattern of inheritance. These two
      findings have only been previously found in the context of monilethrix. The
      coexistence of the two disorders suggests a close association of their genetic
      pathogenesis.

PMID- 11568762
TI  - Open pilot study on oxcarbazepine for the treatment of notalgia paresthetica.
AB  - Notalgia paresthetica is a sensory neuropathy typically presenting with pruritus
      on the back. There is currently no effective treatment for this disorder. We
      describe a single patient who responded to oxcarbazepine, and a subsequent trial
      in another 4 who also responded. Although the number of patients in our study is
      small, we believe further trials are warranted to determine the efficacy of
      oxcarbazepine in this disorder.

PMID- 11568763
TI  - Reversible agranulocytosis associated with oral terbinafine in a pediatric
      patient.
AB  - We report a case of terbinafine-induced agranulocytosis in a pediatric patient.
      This effect was noted 4 weeks after starting terbinafine and resolved within 1
      week without the institution of therapy with granulocyte colony-stimulating
      factor, a course similar to reports in adults. With the incidence of severe side
      effects still unclear in children, this case argues for continued blood
      surveillance during courses of terbinafine and for the confirmation of infection
      before initiation of the drug.

PMID- 11568764
TI  - Hereditary benign intraepithelial dyskeratosis: Report of two cases with
      prominent oral lesions.
AB  - Hereditary benign intraepithelial dyskeratosis is a rare autosomal dominant
      disorder of the oral and ocular mucosa initially described in the Haliwa-Saponi
      Native American tribe of North Carolina. We describe 2 sisters with the
      characteristic oral and ocular findings. This entity should be distinguished from
      several other diseases that cause white lesions in the mouth including white
      sponge nevus.

PMID- 11568765
TI  - Optimal treatment for scabies remains undetermined.

PMID- 11568766
TI  - Cantharidin therapy for molluscum contagiosum in children.

PMID- 11568767
TI  - Should primary cutaneous Ki-1(CD30)-positive anaplastic large cell lymphoma in
      childhood be treated with multiple-agent chemotherapy?

PMID- 11568768
TI  - Evidence-based treatment of alopecia areata.

PMID- 11568769
TI  - Dermatomyositis associated with ovarian transitional cell carcinoma.

PMID- 11568770
TI  - Generalized basaloid follicular hamartoma syndrome.

PMID- 11568772
TI  - Perinatal hospice.
AB  - When the prenatal diagnosis of a lethal fetal anomaly has been established, some
      patients choose to continue their pregnancy. Currently, there is a paucity of
      medical literature addressing the specific management of families in this unique
      circumstance. We propose a model of care that incorporates the strengths of
      prenatal diagnosis, perinatal grief management, and hospice care to address the
      needs of these families. We discuss the identification of candidates for this
      form of care; the multidisciplinary team approach; and the aspects of antepartum,
      intrapartum, and postpartum care. Finally, we discuss some barriers that might
      need to be overcome when attempting to implement perinatal hospice care.

PMID- 11568773
TI  - Pelvic embolization for treatment of hemorrhage related to spontaneous and
      induced abortion.
AB  - OBJECTIVE: Presentation of outcomes of pelvic arterial embolization for
      hemorrhage after spontaneous or induced abortion. STUDY DESIGN: We collected case
      reports of embolization after spontaneous or induced abortion from oral
      presentations and from members of the National Abortion Federation. RESULTS:
      Pelvic arterial embolization was performed for 11 women who had hemorrhage after
      spontaneous or induced abortion, and it was initially successful for all women.
      One woman ultimately required a hysterectomy after unsuccessful repeated
      embolization. Prophylactic embolization was done for 8 women who were at risk for
      hemorrhage from placenta accreta; 4 of these women had subsequent hysterectomies.
      CONCLUSIONS: Selective pelvic arterial embolization may be a successful treatment
      for hemorrhage associated with spontaneous and induced abortion. Embolization can
      be considered before hysterectomy is undertaken for control of hemorrhage. There
      may be a role for prophylactic catheterization or embolization when there is a
      risk of severe hemorrhage.

PMID- 11568774
TI  - Linear measurements in 2-dimensional pelvic floor imaging: the impact of slice
      tilt angles on measurement reproducibility.
AB  - OBJECTIVE: Magnetic resonance imaging techniques have improved the study of
      female pelvic dysfunction. However, disagreements between magnetic resonance
      measurements and their derived 3-dimensional reconstructions were noted. We
      tested the hypothesis that these discrepancies stemmed from variations in
      magnetic resonance acquisition angle. STUDY DESIGN: Images from the pelvis of the
      Visible Human Female (a thinly sliced cadaveric image data set) were obtained.
      Slices in the axial plane were rotated around pivot points in the pelvis to yield
      a set of similar-appearing para-axial images. A parameter that described the
      maximum anterior-posterior dimension of the levator hiatus was defined. This
      levator hiatus parameter was measured on all of the rotated images and compared
      with an expected value that was calculated from trigonometry. The levator hiatus
      was also measured on a group of similar-appearing slices rotated slightly around
      a defined point. RESULTS: In 1 group of slices, expected levator hiatus variation
      was 1.5 to 6.1%, whereas measured variation was 4% to 15%. Among the similar
      appearing rotated slices, 4.8% to 16.0% variations were seen in the levator
      hiatus. CONCLUSION: Identical measurements made on radiologic images can vary
      widely. Slice acquisition must be standardized to avoid errors in data
      comparison.

PMID- 11568775
TI  - Prevalence and predictors of chronic lower genital tract discomfort.
AB  - OBJECTIVE: We sought to determine the prevalence of chronic lower genital tract
      discomfort in the general population and to identify demographic and reproductive
      characteristics associated with this disorder. STUDY DESIGN: We surveyed a random
      sample of 480 women (age range, 20 to 59 years; 60 women for each 5-year age
      category) from 1 Boston area suburban community. Participants were asked to
      complete a 1-page self-administered optically scannable questionnaire that
      pertained to current and previous genital tract discomfort. RESULTS: After 2
      mailings and 1 telephone follow-up, as well as the elimination of 42 ineligible
      women, 303 (70%) questionnaires were returned. Fifty-six women (18.5%) reported a
      history of lower genital tract discomfort that persisted for >3 months.
      Approximately 12% reported a history of chronic knife-like or excessive pain on
      contact to the genital area, whereas 6.6% experienced persistent lower genital
      tract itching or burning. Women who reported their age at menarche to be <or=11
      years old were more than twice as likely to report a history of chronic lower
      genital tract discomfort compared with women who began menses at age 12 or later
      (odds ratio, 2.4; 95% confidence interval, 1.1 to 4.8). Reported pain at the time
      of first use of tampons was associated with an increased risk of chronic lower
      genital tract discomfort later in life (odds ratio, 2.4; 95% confidence interval,
      1.1 to 4.9). CONCLUSIONS: We have shown that women from the general population
      are willing to provide sensitive information on lower genital tract discomfort-a
      first step toward bringing notice to this understudied disorder. In addition, our
      data support the theory that vulvar trauma in early life may influence or serve
      as a marker for risk of subsequent chronic vulvar disorders.

PMID- 11568776
TI  - Management of women with atypical Papanicolaou tests of undetermined significance
      by board-certified gynecologists: discrepancies with published guidelines.
AB  - OBJECTIVE: The Bethesda System introduced 2 categories of atypia: atypical
      glandular cells of undetermined significance (AGUS) and atypical squamous cells
      of undetermined significance (ASCUS). Our objective was to test the hypothesis
      that there is lack of consensus regarding management of women with ASCUS and
      AGUS. STUDY DESIGN: A 2-page survey was mailed in April 1998 to a random sample
      of 491 fellows of the American College of Obstetricians and Gynecologists.
      RESULTS: There were 241 responses (50.6%). For first-time ASCUS, 23.0% of
      respondents would perform colposcopy and 24.4% would repeat the Papanicolaou test
      in <3 months, indicating aggressive management of ASCUS by 47.4% of respondents.
      For recurrent ASCUS, 88.7% followed recommendations to manage with colposcopy.
      For AGUS, 23% repeated the Papanicolaou test and only 43% would manage
      appropriately. For recurrent AGUS, only 25% would perform surgical excision.
      CONCLUSION: Compared with published guidelines, practitioners undermanage
      patients with AGUS and overmanage patients with ASCUS. Further physician
      education appears to be warranted.

PMID- 11568777
TI  - Raloxifene reduces impedance to flow within the uterine artery in early
      postmenopausal women: a 2-year randomized, placebo-controlled, comparative study.
AB  - OBJECTIVE: We sought to investigate the long-term effect of raloxifene and
      continuous combined hormone replacement therapy (ccHRT) on impedance to flow
      within the uterine artery in postmenopausal women. STUDY DESIGN: A prospective,
      randomized, double-blind, placebo-controlled 2-year study was performed in 95
      postmenopausal women. They received either 60 mg of raloxifene daily (raloxifene
      60 group), 150 mg of raloxifene daily (raloxifene 150 group), ccHRT, or placebo.
      At baseline and thereafter every 6 months, color Doppler ultrasonography was used
      to measure the pulsatility index (PI) of the uterine artery. RESULTS: After 24
      months of treatment, compared with placebo, significant decreases were found in
      the PI in the raloxifene 150 group (P = .021) and in the ccHRT group (P = .007).
      In the raloxifene 150 group compared with the placebo group, after 6 and 24
      months, decreases were observed in median PI of -5% and -15%, respectively, and
      in the ccHRT group decreases of -2% and -19%, respectively, were found.
      CONCLUSION: Long-term use of 150 mg of raloxifene daily or ccHRT reduces
      impedance to flow within the uterine artery. This indicates that high-dose
      raloxifene may exert cardiovascular protection.

PMID- 11568778
TI  - A novel X chromosome-linked genetic cause of recurrent spontaneous abortion.
AB  - OBJECTIVE: Unexplained recurrent spontaneous abortion is a common women's health
      problem that affects approximately 1 of every 200 women who wish to have
      children. It has long been assumed that a large proportion of recurrent
      spontaneous abortion results from genetic problems, but no causative genes have
      been identified to date. Here, we tested the hypothesis that a subset of women
      with recurrent spontaneous abortion are carriers of X-linked recessive disorders
      that result in the loss of male pregnancies. STUDY DESIGN: X chromosome
      inactivation patterns, an assay used to detect women who are likely to be
      carriers of X-linked recessive cell-lethal traits, were compared between 105
      female patients with idiopathic recurrent pregnancy loss and 101 women (control
      subjects) with a single successful pregnancy and no history of pregnancy loss.
      Inheritance patterns and gender of offspring were studied in relevant subsets of
      participants. RESULTS: Female patients showed a highly statistically significant
      increase in the frequency of skewed X chromosome inactivation (90%; P < .0005).
      Female patients with highly skewed X chromosome inactivation showed a significant
      decrease in male children. Four of 6 families that were studied showed maternal
      inheritance of the skewed inactivation trait. CONCLUSION: We found the 14% of
      women with unexplained recurrent pregnancy loss show highly skewed X
      inactivation, which suggests that they are carriers of X-linked recessive lethal
      traits. Furthermore, the observed gender bias among women with highly skewed X
      inactivation suggests selective loss of male conceptions, which is consistent
      with an X chromosome-linked genetic defect that leads to cell death or growth
      disadvantage. Identification of such female carriers is important for the
      reproductive counseling and treatment of these women.

PMID- 11568779
TI  - Epidermal clitoral inclusion cyst after type I female genital mutilation.
AB  - OBJECTIVE: To document the occurrence of long-term sequelae after type I female
      genital mutilation (FGM) and describe the surgical treatment of epidermal
      clitoral inclusion cyst. STUDY DESIGN: Twenty-one women presented with epidermal
      clitoral inclusion cyst after type I FGM at the Department of Obstetrics and
      Gynecology at King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia. The
      duration (mean +/- SD, range) of symptoms was 10.3 +/- 5.4, 2 to 20 years. They
      were treated by excision of the cyst with particular attention to preserve the
      remaining part of the clitoris. The technique involves making a vertical incision
      in the skin, dissecting and excising the cyst, removing the excessive skin, and
      reapproximating the skin edges. RESULTS: The procedure was done on all patients
      without intraoperative complications. All except one were discharged home on the
      second postoperative day. Follow-up showed no recurrence of symptoms. CONCLUSION:
      Long-term sequelae can occur after type I FGM. The surgical treatment of clitoral
      inclusion cyst is simple and effective.

PMID- 11568780
TI  - No evidence for lipid peroxidation in severe preeclampsia.
AB  - OBJECTIVE: This study was undertaken to address the role of oxidative stress in
      preeclampsia. STUDY DESIGN: We measured urinary 8,12-iso-iPF(2alpha)-VI, a
      chemically stable, free-radical catalyzed product, in a case control study of
      severe preeclampsia nested within the trial of Calcium for Preeclampsia
      Prevention. Cases included 29 women who developed severe preeclampsia and from
      whom urine had been obtained 10 to 20 weeks before the diagnosis of preeclampsia,
      3 to 9 weeks before, and 1 day before through delivery. Controls did not develop
      hypertension or proteinuria and were matched to cases by center, gestational age
      at each of 3 corresponding urine collections, and date of enrollment. RESULTS:
      Urinary 8,12-iso -iPF(2alpha)-VI did not differ significantly between cases and
      controls before or at diagnosis of preeclampsia, nor did it vary with gestational
      age. CONCLUSIONS: These results call into question the importance of oxidative
      stress in the disease and the biochemical rationale for clinical trials of
      antioxidants to prevent and treat preeclampsia.

PMID- 11568781
TI  - Reduced binding of progesterone receptor to its nuclear response element after
      human labor onset.
AB  - OBJECTIVE: There is indirect evidence of decreased progesterone-activated
      transcription after human labor onset. Binding of the progesterone receptor to
      its response element is a prerequisite of progesterone-activated transcription.
      We established an assay to investigate whether there is reduced binding of
      progesterone receptor to its nuclear response element after, compared with
      before, labor onset. STUDY DESIGN: The binding of progesterone receptor from the
      decidua to its nuclear response element was measured in gel shift assays. Tissues
      from 52 patients who were term, preterm, in labor, and not in labor were
      compared. RESULTS: A 9-fold decrease in progesterone receptor binding to its
      response element was observed in tissues obtained after, compared with before,
      the onset of labor (P = .0008). In both preterm and term not-in-labor tissues,
      binding was higher than for in-labor tissues (P = .0172 for preterm; P = .0147
      for term, Mann-Whitney U test). CONCLUSION: These findings provide a mechanism
      for the effective withdrawal of progesterone in human parturition.

PMID- 11568782
TI  - An in vitro study of antibacterial properties of the cervical mucus plug in
      pregnancy.
AB  - OBJECTIVE: To evaluate whether cervical mucus plugs are antibacterial in vitro.
      STUDY DESIGN: Cervical mucus plugs from 56 healthy women in labor were studied by
      2 different antimicrobial assays: (1) analysis of the inhibition by the cervical
      mucus plug of several gram-positive and gram-negative bacteria by overlaying the
      cervical mucus plug onto an agar plate with imbedded bacteria, and (2)
      determination of the antibacterial property of the cervical mucus plug material
      by radial diffusion assay with group B Streptococcus and Escherichia coli.
      RESULTS: In the agar overlay assay, there was complete inhibition of clinical
      isolates of Staphylococcus saprophyticus, E coli, and Pseudomonas aeruginosa and
      patient-variable partial-to-complete inhibition of Enterococcus faecium,
      Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus agalactiae. In
      the radial diffusion assay, cervical mucus plugs had activity toward group B
      Streptococcus equivalent to 0.075 microg/mL of gentamicin and toward E coli
      equivalent to 0.5 microg/mL of gentamicin. CONCLUSION: A low-molecular substance
      with antibacterial activity in the cervical mucus plug may protect the fetus
      against ascending infections.

PMID- 11568783
TI  - Population pharmacokinetics of magnesium in preeclampsia.
AB  - OBJECTIVE: The purpose of this study was to determine the population
      pharmacokinetics of magnesium from sparse observational data in patients with
      preeclampsia. STUDY DESIGN: Serum magnesium concentrations (1-11 per patient)
      were obtained retrospectively from the records of 116 patients with preeclampsia
      who had a loading dose of magnesium sulfate (16 or 20 mmol), followed by a
      maintenance dose (1 mmol/h) over an average of 28 hours. Population clearance,
      volume of distribution, and the baseline magnesium concentration were estimated
      using the NONMEM program. RESULTS: The following population typical values,
      together with the interpatient variability (expressed as coefficient of
      variation) were obtained with the use of a 1-compartment model: systemic
      clearance, 4.28 L/h (37.3%); volume of distribution, 32.3 L (32.1%); baseline
      concentration, 0.811 mmol/L (18.5%). The average half-life was 5.2 hours. Clonus
      was not obtunded in 4 patients whose serum magnesium concentrations were similar
      to the average concentration of 1.7 mmol/L. The variability remaining unexplained
      after the population model was fitted to the data was 6.5% to 10.8%. CONCLUSION:
      This study extended knowledge of the pharmacokinetic disposition of magnesium in
      preeclampsia. The results are potentially useful for the calculation of loading
      and maintenance doses, particularly when the relationship between serum
      concentration and effect in preeclampsia is clarified.

PMID- 11568784
TI  - Insertion-deletion polymorphism in the gene for angiotensin-converting enzyme is
      associated with obstetric cholestasis but not with preeclampsia.
AB  - OBJECTIVE: Our purpose was to investigate the contribution of angiotensin
      converting enzyme insertion-deletion polymorphism in the development of obstetric
      complications. STUDY DESIGN: In a retrospective case-control study, angiotensin
      converting enzyme insertion-deletion polymorphism was investigated in a control
      group of healthy women (n = 115) and in a group of women diagnosed with
      preeclampsia (n = 133) and obstetric cholestasis (n = 57). Polymerase chain
      reaction detection of insertion-deletion polymorphism was used to determine the
      presence of the two angiotensin-converting enzyme alleles in the groups; the
      frequencies in the general population in our area are presented for comparison.
      RESULTS: The frequency of the D allele was 43.9% among women with obstetric
      cholestasis and 27% among healthy fertile women, which is close to the rate in
      the general population in our area (28%). The odds ratio for obstetric
      cholestasis associated with the DD genotype was 2.12 (95% CI, 1.08-4.12) compared
      with the pooled II and ID genotypes (P = .03). Neither the ID genotype
      distributions nor the allele frequencies differed significantly between
      preeclamptic and normotensive pregnancies (P = .36). CONCLUSION: The present data
      indicate that the DD genotype is a genetic marker associated with an elevated
      risk of obstetric cholestasis, but this polymorphism of the angiotensin
      converting enzyme gene is unlikely to play any significant role in preeclampsia.

PMID- 11568785
TI  - One or two hours postprandial glucose measurements: are they the same?
AB  - OBJECTIVE: This study was undertaken to compare the rate of abnormal glucose
      levels measured after 1 hour (>140 mg%) with those measured after 2 hours (>120
      mg%) postprandially in women with gestational diabetes mellitus (GDM). STUDY
      DESIGN: Sixty-eight women were included in this study. All had GDM based on the
      criteria of Carpenter-Coustan. Women with fasting glucose levels of 105 mg% or
      more were excluded from the study. All women were initially treated by diet. All
      women measured daily capillary blood glucose levels when fasting as well as 1
      hour and 2 hours postprandially for 1 week, immediately after diagnosis of GDM.
      Glucose levels were obtained by memory-based glucometers. All women were followed
      in a specialized gestational-diabetes clinic throughout the pregnancy. Insulin
      therapy was started on an individual basis according to common clinical criteria.
      Epidemiologic and perinatal data were collected from medical charts. RESULTS: The
      average age of the women was 30.8 +/- 5.4 years. Thirty-five percent of
      participants were primipara. The mean gestational age at diagnosis was 28.8 +/-
      5.4 weeks. Glucose measurements included 618 readings during fasting and 2730
      either 1 hour or 2 hours postprandial. Rates of abnormal glucose (>95 mg% when
      fasting; >140 mg% 1 hour or >120 mg% 2 hours after each meal) per person were the
      following: fasting, 27.1% abnormal glucose measurements; postbreakfast, 22.4%
      abnormal levels after 1 and 8.5% after 2 hours (P < .01); postlunch, 16.4%
      abnormal levels after 1 hour and 18.2% after 2 hours (not significant);
      postdinner, 16.3% abnormal levels after 1 hour and 30.1% after 2 hours (P < .01).
      CONCLUSION: The rate of abnormal values was 2.5-fold greater 1 hour postbreakfast
      than 2 hours postbreakfast, in contrast to an opposite ratio of a 2-fold increase
      in the rate of abnormal values 2 hours postdinner versus 1 hour postdinner.
      Therefore, differential measurement (1 hour after breakfast and 2 hours after
      dinner) might impose stricter criteria for controlling blood glucose levels.
      Further clinical research should explore whether differential measurements might
      reduce the rate of diabetes-associated complications.

PMID- 11568786
TI  - A longitudinal study of quantitative uterine blood flow with the use of color
      power angiography in appropriate for gestational age pregnancies.
AB  - OBJECTIVE: The purpose of this study was to examine longitudinally changes in
      quantified blood volume flow in the uterine arteries during pregnancy with the
      use of color power angiography. STUDY DESIGN: Color power angiography was used to
      quantify volume flow in the uterine arteries of 57 women with singleton
      uncomplicated pregnancies between 20 and 38 weeks' gestation. Comparisons were
      made between blood flow in the 2 arteries in relation to the location of the
      placenta. Linear regression models were used to estimate gestational age derived
      volumetric changes in these vessels. RESULTS: The diameter of the uterine
      arteries increased from 2.6 mm (SD, 0.2 mm) at 20 weeks to 4.8 mm (SD, 0.7 mm) at
      38 weeks of gestation. The total uterine artery blood volume flow increased from
      513 mL/min (SD, 127 mL/min) at 20 weeks to 970 mL/min (SD, 193 mL/min) at 38
      weeks. The rate of increase was maximum between 20 and 24 weeks (39 mL/min per
      week). The laterality of the placenta significantly affected the diameter and
      blood volume flow in each uterine artery. The diameters on the ipsilateral side
      were significantly greater (by 10.8% +/- 2.4%) than the diameters on the
      contralateral side at all gestations (P < .05). Similarly, blood volume flow was
      significantly greater (by 17.8% +/- 2.2%) on the ipsilateral side at all
      gestations (P < .05). There were, however, no statistically significant
      differences between the vessel diameters and blood volume flow in those cases in
      which the placenta was central. Total uterine artery volume flow per kilogram of
      estimated fetal weight decreased from 1544 mL/kg per minute at 20 weeks to 296
      mL/kg per minute at 38 weeks of gestation. CONCLUSION: Total quantified uterine
      artery blood volume flow increases while blood flow per kilogram of fetal weight
      decreases with gestation. Blood volume flow in the ipsilateral artery to the
      placenta was significantly higher than that in the contralateral artery.
      Calculating total uterine artery volume flow by doubling the blood flow from 1
      artery (as was previously done) may therefore either result in an over or
      underestimation, depending on the relationship between the vessel and the
      laterality of the placenta. Color power angiography is a simple noninvasive tool
      for determining uterine artery blood volume flow.

PMID- 11568787
TI  - Growth hormone treatment after cesarean delivery in rats increases the strength
      of the uterine scar.
AB  - OBJECTIVE: We sought to determine whether postcesarean treatment of rats with
      growth hormone (GH) affected the strength of the uterine incision in the
      puerperium and in a subsequent pregnancy. STUDY DESIGN: Forty-eight near-term
      pregnant rats were delivered by cesarean section. Half received subcutaneous
      recombinant human GH (2.0 mg x kg(-1) x d(-1)) for 7 days; control animals
      received saline injections. Four weeks after delivery, the uterine bursting
      pressure was determined in 5 treated and 5 control animals. Eight rats in each
      group were used to study uterine hydroxyproline concentrations and the histologic
      characteristics of the scar. Twenty-two animals were rebred 30 to 40 days after
      their cesarean sections. After repeat cesarean delivery, on day 19, the bursting
      pressure and hydroxyproline concentrations of the previous hysterotomy scar were
      determined. RESULTS: The uterine horn bursting pressure in the GH-treated animals
      was significantly greater than that in the control animals both 28 days
      postpartum and near term in a subsequent pregnancy. The uterine hydroxyproline
      concentrations followed the same pattern. Histologic study of the scars showed
      they were thicker and had less cellularity in the treated animals than in the
      control animals. CONCLUSION: Postcesarean treatment with GH increased the
      bursting strength of rat uterine incisions. This effect was accompanied by a
      significant increase in collagen content and persisted through a subsequent
      pregnancy.

PMID- 11568788
TI  - Twenty-four-hour automated blood pressure monitoring as a predictor of
      preeclampsia.
AB  - OBJECTIVE: The purpose of this study was to determine the predictive ability of
      parameters of 24-hour ambulatory blood pressure monitoring for the development of
      preeclampsia or gestational hypertension in women who are already considered at
      risk for these disorders. STUDY DESIGN: One hundred twenty-two pregnant women who
      were considered high risk for the development of preeclampsia underwent 24-hour
      ambulatory blood pressure monitoring between 18 and 30 weeks gestation, while
      their condition was normotensive according to routine mercury sphygmomanometry.
      One hundred sixty-four healthy primigravid women who were considered at usual
      risk for preeclampsia underwent the same tests as a parallel study. Routine blood
      pressure, awake and sleep average blood pressure, and 24-hour mean average blood
      pressure were entered into multiple logistic regression as predictors of either
      preeclampsia or gestational hypertension; significant variables were then tested
      by a series of receiver operator curves. RESULTS: Eight percent of usual risk and
      45% of high risk women experienced the development of preeclampsia or gestational
      hypertension. In both groups, the average routine mercury blood pressure and
      awake, sleeping, and 24-hour ambulatory blood pressure monitoring-derived blood
      pressure were significantly higher in women who later experienced the development
      of preeclampsia or gestational hypertension. In usual risk women, 24-hour
      systolic blood pressure of >or=115 mm Hg and sleeping systolic blood pressure of
      >or=106 mm Hg were predictive of later preeclampsia or gestational hypertension,
      but sensitivities were low (77% and 54%, respectively). In high risk women,
      sleeping diastolic blood pressure of >or=62 mm Hg and sleeping mean arterial
      pressure of >or=79 mm Hg were predictive of preeclampsia or gestational
      hypertension, but again sensitivities were low (70% and 65%, respectively).
      CONCLUSION: Awake and sleeping blood pressure are higher in midpregnancy in women
      who later experience the development of preeclampsia or gestational hypertension.
      Twenty-four-hour ambulatory blood pressure monitoring provides a noninvasive
      method of selecting some of these women, but this test has a sensitivity no
      better than that of other predictive tests, even in women at high risk for
      preeclampsia.

PMID- 11568789
TI  - Perinatal care regionalization and low birth weight infant mortality rates in
      Alaska.
AB  - OBJECTIVE: The purpose of this study was to determine the extent to which the
      failure of non-tertiary care hospitals to appropriately triage and refer pregnant
      women and newborns contributes to low birth weight infant death in Alaska. STUDY
      DESIGN: Birth certificates from 1993 to 1997 were reviewed for all 2809 infants
      who were born at less than 2500 g. Death certificates and maternal and infant
      medical charts were reviewed for all 168 infant deaths that occurred during this
      time. RESULTS: Mother-infant pairs who received all care at Alaska's single
      tertiary care center had a lower mortality rate than those who received some care
      at a non-tertiary care center (risk ratio, 1.5; 95% confidence interval, 0.86
      2.6). Despite this, only 4% of deaths among low birth weight infants (all <1500
      g) were associated with care decisions at non-tertiary centers; none of these
      deaths involved intentional inappropriate retention of infants or mothers.
      CONCLUSION: Further emphasizing perinatal care regionalization (including for
      infants 1500-2499 g birth weight) is unlikely to substantially decrease low birth
      weight infant mortality rates.

PMID- 11568790
TI  - A randomized trial that compared oral cefixime and intramuscular ceftriaxone for
      the treatment of gonorrhea in pregnancy.
AB  - OBJECTIVE: The purpose of this study was to evaluate prospectively the Centers
      for Disease Control recommendations for the treatment of gonococcal infection in
      pregnancy. STUDY DESIGN: One hundred sixty-one women who were referred with
      probable endocervical gonorrhea underwent pretreatment endocervical, anal, and
      oral cultures for Neisseria gonorrhoeae. The women were randomly assigned to
      receive ceftriaxone 125 mg intramuscularly or cefixime 400 mg orally. Treatment
      was open and in a 1:1 distribution. There were 95 evaluable patients. The tests
      of cure cultures were performed 4 to 10 days after treatment. RESULTS: Eighty-six
      women (91%) had endocervical infection; 39 women (41%) had anal infection, and 11
      women (12%) had pharyngeal infection. Fifty of 95 women (53%) had concomitant
      endocervical chlamydial infection. The overall efficacy was 91 of 95 subjects
      (95.8%; 95% CI, 89.6%-98.8%). Ceftriaxone was effective in 41 of 43 cases (95%;
      95% CI, 84.2%-99.4%), and cefixime was effective in 50 of 52 cases (96%; 95% CI,
      86.8%-99.5%). No significant difference was noted in the overall efficacy or by
      site of infection. Three of the 4 women who experienced treatment failures
      admitted to unprotected intercourse before their test of cure culture.
      CONCLUSION: Both intramuscular ceftriaxone 125 mg and oral cefixime 400 mg appear
      to be effective for the treatment of gonococcal infection in pregnancy.

PMID- 11568791
TI  - Enoxaparin treatment in women with mechanical heart valves during pregnancy.
AB  - OBJECTIVE: This prospective audit reports pregnancy outcomes, anticoagulation
      complications, and anti-Xa levels in women with mechanical heart valves who were
      treated with therapeutic enoxaparin plus aspirin during pregnancy. STUDY DESIGN:
      Between 1997 and 1999, 11 women with mechanical heart valves were treated with
      enoxaparin, 1 mg/kg twice daily, and aspirin, 100 to 150 mg daily during 14
      pregnancies. Predose and 4-hour postdose anti-Xa levels were monitored monthly.
      RESULTS: There were 9 live births, 3 miscarriages, and 2 terminations. In 48
      months of enoxaparin treatment, one woman who had a documented valve thrombosis
      when she presented at 8 weeks' gestation also had a valve thrombosis at 20 weeks'
      gestation. There were no enoxaparin-related hemorrhagic complications. Mean (SD)
      anti-Xa levels were 0.46 (0.12) U/mL predose and 0.89 (0.22) U/mL 4 hours
      postdose. CONCLUSION: Successful pregnancy outcome may be achieved with
      therapeutic subcutaneous enoxaparin, but its efficacy at preventing valve
      thrombosis remains uncertain. Further data are required before use of enoxaparin
      during pregnancy in women with mechanical heart valves can be recommended.

PMID- 11568792
TI  - The role of endothelium-derived hyperpolarizing factor in the regulation of the
      uterine circulation in pregnant rats.
AB  - OBJECTIVE: The purpose of this study was to determine whether endothelium-derived
      hyperpolarizing factor regulates rat uterine circulation in pregnant rats. STUDY
      DESIGN: Intact isolated uterine vascular beds from late pregnant rats were
      perfused in situ with Krebs buffer that contained dextran, indomethacin, N-nitro
      L-arginine methyl ester, and phenylephrine. Endothelium-derived hyperpolarizing
      factor-induced decreases in perfusion pressure in response to acetylcholine were
      analyzed. RESULTS: The decrease in perfusion pressure induced by endothelium
      derived hyperpolarizing factor was significantly attenuated by 4-aminopyridine
      and was abolished by a combination of 4-aminopyridine and tetraethylammonium.
      Endothelium-derived hyperpolarizing factor-induced decrease in perfusion pressure
      was abolished by potassium chloride and attenuated by miconazole, but not
      linoleyl hydroxamic acid. Endothelium-derived hyperpolarizing factor-induced
      decrease in perfusion pressure persisted after perfusion with solutions that
      contained 2 inhibitors of nitric oxide synthase and a scavenger of nitric oxide.
      Nitric oxide exerted negative feedback on the endothelium-derived hyperpolarizing
      factor effects. CONCLUSION: In the pregnant rat uterine vascular beds,
      endothelium-derived hyperpolarizing factor release is activated by a delayed
      rectifier type of voltage-sensitive potassium channel. Endothelium-derived
      hyperpolarizing factor does not seem to be related to nitric oxide or to products
      of lipoxygenase or cytochrome p450 mono-oxygenase pathways of arachidonic acid
      metabolism.

PMID- 11568793
TI  - The Preterm Prediction Study: toward a multiple-marker test for spontaneous
      preterm birth.
AB  - OBJECTIVE: The Preterm Prediction Study evaluated 28 potential biologic markers
      for spontaneous preterm birth in asymptomatic women at 23 to 24 weeks gestational
      age. This analysis compares those markers individually and in combination for an
      association with spontaneous preterm birth at <32 and <35 weeks gestational age.
      STUDY DESIGN: With the use of a nested case-control design from an original
      cohort study of 2929 women, results of tests from 50 women with a spontaneous
      preterm birth at <32 weeks and 127 women with a spontaneous preterm birth at <35
      weeks were compared with results from matched-term control subjects. RESULTS: In
      the univariate analysis, the most potent markers that are associated with
      spontaneous preterm birth at <32 weeks by odds ratio were a positive cervical
      vaginal fetal fibronectin test (odds ratio, 32.7) and <10th percentile cervical
      length (odds ratio, 5.8), and in serum, >90th percentiles of alpha-fetoprotein
      (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and >75th
      percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results
      for spontaneous preterm birth at <35 weeks were generally similar but not as
      strong. Univariate and multivariate logistic regression analyses demonstrated
      little interaction among the tests in their association with spontaneous preterm
      birth. Combinations of the 5 markers were evaluated for their association with
      <32 weeks spontaneous preterm birth. Ninety-three percent of case patients had at
      least 1 positive test result versus 34% of control subjects (odds ratio, 24.0;
      95% CI, 6.4-93.4). Among the case patients, 59% had >or=2 positive test results
      versus 2.4% of control subjects (odds ratio, 56.5; 95% CI, 7.1-451.7). If a
      cutoff of 3 positive test results was used, 20% of case patients and none of the
      control subjects had positive test results (P < .002). With the use of only the 3
      serum tests (alkaline phosphatase, alpha-fetoprotein, and granulocyte colony
      stimulating factor), any positive test identified 81% of cases versus 22% of
      control subjects (odds ratio, 14.7; 95% CI, 5.0-42.7). For spontaneous preterm
      birth at <35 weeks gestation, any 2 positive tests identified 43% of cases and 6%
      of control subjects (odds ratio, 11.2; 95% CI, 4.8-26.2). CONCLUSION: Overlap
      among the strongest biologic markers for spontaneous preterm birth is small. This
      suggests that the use of tests such as maternal serum alpha-fetoprotein, alkaline
      phosphatase, and granulocyte colony-stimulating factor as a group or adding their
      results to fetal fibronectin test and cervical length test results may enhance
      our ability to predict spontaneous preterm birth and that the development of a
      multiple-marker test for spontaneous preterm birth is feasible.

PMID- 11568794
TI  - Perinatal correlates and neonatal outcomes of small for gestational age infants
      born at term gestation.
AB  - OBJECTIVE: We sought to examine the current perinatal correlates and neonatal
      morbidity associated with intrauterine growth failure among neonates born at term
      gestation. STUDY DESIGN: We compared 372 small for gestational age (SGA, birth
      weight <10th percentile) infants born at term gestation to 372 appropriate for
      gestational age controls (AGA, birth weight 10th to 90th percentile) matched by
      sex, race, and gestational age within 2 weeks. RESULTS: Compared with AGA
      controls, significant (P < .05) maternal risk factors for SGA status included
      single marital status (59% versus 53%), lower prepregnancy weight (144 +/- 41 lbs
      versus 153 +/- 40 lbs), lower weight gain during pregnancy (29 +/- 15 lbs versus
      33 +/- 15 lbs), smoking (25% versus 17%), hypertension (14% versus 7%), and
      multiple gestation (9% versus 2%). Mothers of SGA infants were more likely to
      undergo multiple (>or=3) antenatal ultrasound evaluations (19% versus 7%),
      biophysical profile monitoring (11% versus 4%), and oxytocin delivery induction
      (28% versus 16%) (P < .05). Pediatrician attendance was more common among SGA
      deliveries (50% versus 37%, P < .05). SGA infants had significantly higher rates
      of hypothermia (18% versus 6%) and symptomatic hypoglycemia (5% versus 1%). These
      neonatal problems remained significant even when medical or pathologic causes of
      intrauterine growth failure, including pregnancy hypertension, multiple
      gestation, and congenital malformations, were excluded. CONCLUSION: Despite
      higher rates of pregnancy complications among mothers of SGA infants, the rates
      of neonatal adverse outcomes are low. However, SGA infants remain at risk for
      hypothermia and hypoglycemia and require careful neonatal surveillance.

PMID- 11568795
TI  - Ethnicity, nutrition, and birth outcomes in nulliparous women.
AB  - OBJECTIVE: Ethnic differences in birth outcomes are well established, but it is
      not clear whether differences in nutrition may partly explain unaccounted
      differences in birth outcomes. Our purpose was to evaluate the relationship of
      nutrition to ethnic differences in birth outcomes. STUDY DESIGN: This was a
      multicenter, prospective study of 4589 healthy nulliparous women who were
      enrolled in the Calcium for Preeclampsia Prevention trial conducted from 1992 to
      1995. Main outcome measures were birth weight, gestational age at delivery,
      preterm birth, and small for gestational age birth after the data were controlled
      for maternal characteristics and intake of total calories, protein, carbohydrate,
      fat, and 13 vitamin and mineral constituents that were obtained from a 24-hour
      recall at 13 to 21 weeks' gestation. RESULTS: Black and non-Hispanic white women
      differed significantly in birth outcomes, with odds ratios of 2.06 (95%
      confidence interval, 1.48-2.86) for small for gestational age and 1.38 (95%
      confidence interval, 0.98-1.95) for preterm birth, after adjustment for maternal
      characteristics. These odds ratios were hardly changed by the further adjustment
      for all nutritional variables, even though there were substantial nutritional
      differences between black and white women. Differences in birth outcomes between
      Hispanic and non-Hispanic white women were small. Hispanic women who spoke only
      Spanish were better nourished than those Hispanic women who spoke English, but
      this had only a modest effect on birth outcomes. CONCLUSION: Nutritional
      variation among women in the United States does not appear to have a significant
      role in the explanation of ethnic differences in birth outcomes.

PMID- 11568796
TI  - The severity of immune fetal hydrops is predictive of fetal outcome after
      intrauterine treatment.
AB  - OBJECTIVE: This study was undertaken to test the hypothesis that the degree of
      immune fetal hydrops predicts outcome in red blood cell-alloimmunized
      pregnancies. STUDY DESIGN: In an 11-year period, 213 fetuses received 599
      intrauterine transfusions. The outcome of 208 pregnancies, including two pairs of
      twins, was analyzed in a retrospective study. Eighty fetuses demonstrated
      ultrasonographic signs of hydrops at the start of treatment; 42 of these were
      classified as mildly hydropic and 38 were classified as severely hydropic.
      Reversal of hydrops as a result of treatment, survival, and neonatal morbidity
      was studied. RESULTS: The overall survival rate of fetuses with hydrops was 78%.
      Of the fetuses with mild hydrops, 98% survived, whereas in cases of severe
      hydrops the survival rate was 55%. Intrauterine reversal of hydrops occurred in
      65% of the fetuses with hydrops. The reversal rate was 88% in fetuses with mild
      hydrops and 39% in fetuses classified as severely hydropic. After reversal of
      hydrops, almost all of the fetuses survived (98%), whereas in cases of persistent
      hydrops outcome was unfavorable, with a survival rate of 39% for all fetuses and
      26% for fetuses classified as severely hydropic. CONCLUSION: In contrast with
      severe hydrops, there is a high rate of reversal of mild hydrops after adequate
      treatment. In our study 98% of fetuses survived after reversal of hydrops. To
      improve the outcome of red blood cell-alloimmunized pregnancies, early diagnosis
      of fetal anemia and referral to a specialized center are important; these steps
      enable the start of intrauterine treatment when hydrops is absent or still mild.

PMID- 11568797
TI  - Fetal umbilical cord oxygen values and birth to placental weight ratio in
      relation to size at birth.
AB  - OBJECTIVE: Our purpose was to examine regulatory linkages between fetal
      oxygenation and fetal and placental growth. We determined umbilical cord PO (2)
      and oxygen saturation, fractional oxygen extraction, and birth to placental
      weight ratio values in relation to size at birth for a large tertiary hospital
      population delivering at term. STUDY DESIGN: The computerized perinatal database
      of St Joseph's Health Care London, London, Ontario, was used to obtain the
      umbilical cord gases, pH, birth weight, placental weight, and other selected
      information for all term, singleton, liveborn infants between January 1990 and
      December 1999 (N = 27,043). Oxygen saturation values were calculated from the
      umbilical cord PO(2) and pH data with a previously derived empirical equation;
      fractional oxygen extraction values were calculated from the umbilical cord
      oxygen saturation data. Size at birth was divided into the following 5 birth
      weight categories using neonatal growth standards: fetal growth restriction, <3%;
      borderline fetal growth restriction, >or=3% and <10%; appropriate for gestational
      age, >or=10% and <or=90%; borderline large for gestational age, >90% and <or=97%;
      large for gestational age, >97%. RESULTS: Infants in the borderline fetal growth
      restriction and fetal growth restriction groups had umbilical vein and artery
      PO(2) and oxygen saturation values that were stepwise lower than respective
      values for infants in the appropriate for gestational age group. Conversely,
      infants in the borderline large for gestational age and large for gestational age
      groups had umbilical vein PO(2) and oxygen saturation values that were stepwise
      higher than respective appropriate for gestational age group values; infants in
      these groups showed no change in arterial PO (2) and oxygen saturation values.
      Therefore infants in the borderline fetal growth restriction and fetal growth
      restriction groups had fractional oxygen extraction values that were stepwise
      higher than the appropriate for gestational age group value, whereas values for
      infants in the borderline large for gestational age and large for gestational age
      groups remained unchanged. Birth weight was disproportional to placental weight
      for infants in the borderline fetal growth restriction and fetal growth
      restriction groups when compared with that of the infants in the appropriate for
      gestational age group, with the birth to placental weight ratio values stepwise
      decreased. Conversely, birth weight was proportional to placental weight for
      infants in the borderline large for gestational age and large for gestational age
      groups with the birth to placental weight ratio values thus unchanged when
      compared with that of the infants in the appropriate for gestational age group.
      CONCLUSION: We conclude that fetal oxygenation is related to size at birth across
      the entire range of birth weights as studied at term from macrosomic to growth
      restricted infants; this conclusion supports oxygen as a primary determinant of
      fetal growth. However, there are differences in the linkage between fetal
      oxygenation and metabolic rate or growth for these cohort groups that may relate
      to underlying etiologic processes.

PMID- 11568798
TI  - A less invasive treatment strategy to prevent intracranial hemorrhage in fetal
      and neonatal alloimmune thrombocytopenia.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether a less invasive
      treatment strategy results in a higher platelet count of the neonate and prevents
      intracranial hemorrhage in pregnant women who are at risk for fetal or neonatal
      alloimmune thrombocytopenia. STUDY DESIGN: Between March 1989 and August 2000, 48
      women with 56 pregnancies were treated. The population was divided into groups. A
      diagnostic fetal blood sample was taken in 7 cases that had a history of a
      sibling with an intracranial hemorrhage (group I; n = 8); treatment was provided,
      when necessary, with platelet transfusions and maternal administration of
      immunoglobulin. The other 48 cases, with a history of a sibling with severe
      thrombocytopenia but without intracranial hemorrhage, were retrospectively
      divided into group IIa (n = 16) and IIb (n = 32). In group IIa, at least 2
      diagnostic fetal blood samples were taken, and when necessary, intrauterine
      platelet transfusion and immunoglobulin were administered (invasive treatment).
      In group IIb, no initial diagnostic fetal blood sampling was performed
      (noninvasive treatment). In 23 cases, immunoglobulin was administered, which was
      followed by predelivery fetal blood sampling in 8 cases. In 9 cases, only
      predelivery fetal blood sampling was performed, when necessary, followed by
      intrauterine platelet transfusion. RESULTS: Results of our noninvasive treatment
      strategy were comparable to results of the invasive method in the prevention of
      intracranial hemorrhage (intracranial hemorrhage was not observed). In addition,
      there was an increasing trend in median platelet count and a lower number of
      cases with severe thrombocytopenia (<50 x 10(9)/L) in the noninvasive compared
      with the invasive treatment group (median platelet count, 92 and 31 x 10(9)/L,
      respectively). CONCLUSION: Our results indicate that a less invasive treatment
      strategy in patients who are at risk for fetal or neonatal alloimmune
      thrombocytopenia and who have no history of a previous child who was affected
      with intracranial hemorrhage seems justified.

PMID- 11568799
TI  - Selective photocoagulation of communicating vessels in the treatment of
      monochorionic twins with selective growth retardation.
AB  - OBJECTIVE: Current treatment of patients with selective intrauterine growth
      retardation in monochorionic twins includes expectant management, termination of
      pregnancy, or umbilical-cord occlusion. The purpose of this study was to assess
      the outcome of monochorionic twins with selective intrauterine growth retardation
      who were treated with selective laser photocoagulation of the communicating
      vessels. STUDY DESIGN: Monochorionic twin pregnancies with selective intrauterine
      growth retardation at less than 26 weeks were eligible for the study. Selective
      intrauterine growth retardation was defined as <10th percentile for gestational
      age. Absent or reverse end-diastolic velocity in the umbilical artery of the twin
      with selective intrauterine growth retardation was required for eligibility after
      January 2000. RESULTS: Thirty patients met the criteria for the study: 17
      patients were treated expectantly (group I); 2 patients underwent umbilical-cord
      ligation of the twin with selective intrauterine growth retardation, and 11
      patients underwent selective laser photocoagulation of the communicating vessels
      (group II). Survival rates for at least 1 fetus were no different between groups
      I and II (14/17 [82.3%] vs 8/11 [72.3%]; P = .4). However, concomitant demise of
      the co-twin occurred in 4 of 7 patients, and iatrogenic premature delivery for
      deterioration of the twin with selective intrauterine growth retardation was
      necessary in 2 patients in group I, which resulted in significant neonatal
      morbidity. Of the live-born babies, neurologic handicap was present in 3 of 22
      babies (13.6%) versus 0 of 12 in groups I and II, respectively (P < .0001).
      CONCLUSION: Selective intrauterine growth retardation in monochorionic twins can
      be effectively treated with selective laser photocoagulation of the communicating
      vessels. By unlinking the circulations between the fetuses, the pregnancy is
      rendered "functionally" dichorionic, which improves pregnancy treatment and
      results in decreased neonatal morbidity. This approach constitutes a new valuable
      alternative in the treatment of monochorionic twin pregnancies with selective
      intrauterine growth retardation. A randomized clinical trial of expectant
      treatment versus selective laser photocoagulation of the communicating vessels
      for monochorionic selective intrauterine growth retardation can be considered.

PMID- 11568800
TI  - Influence of labor on fetoplacental adrenomedullin concentrations.
AB  - OBJECTIVE: Circulating adrenomedullin is increased in pregnancy, and placental
      and fetal membranes participate significantly in its secretion. Recent studies
      have suggested a potential role for this peptide in the regulation of
      fetoplacental circulation and placental hormonal secretion. Because
      adrenomedullin acts also as a uterorelaxant in rats, this study was designed to
      investigate whether fetoplacental adrenomedullin production changes with human
      labor, either at term or preterm. STUDY DESIGN: Eighty pregnant women grouped
      according to gestational age and presence of labor were studied. Adrenomedullin
      concentrations in plasma, amniotic fluid, and placental tissue extracts were
      measured by means of radioimmunoassay and immunohistochemistry. In addition, the
      ability of amnion and chorion-decidua to secrete adrenomedullin was investigated
      in vitro. RESULTS: Adrenomedullin concentrations in amniotic fluid were higher in
      preterm labor, whereas no differences were found in adrenomedullin expression or
      concentrations in tissues or in maternal and fetal plasma between vaginal
      delivery or elective cesarean section, both at term and preterm. During term
      labor (8 patients), maternal plasma adrenomedullin concentration decreased with
      advancing cervical dilatation, being 173 pg/mL at the beginning of the active
      stage of labor and 57 pg/mL at the time of delivery. Adrenomedullin concentration
      in the medium of amnion- and chorion-decidua-cultured cells was higher after
      vaginal delivery. CONCLUSION: These results suggest that a decrease in
      adrenomedullin production is not involved in the onset of labor in human subjects
      but rather that it may play a role other than that of a myometrial relaxant in
      human parturition.

PMID- 11568801
TI  - Complicated monochorionic twin pregnancies: experience with bipolar cord
      coagulation.
AB  - OBJECTIVE: The purpose of the study was to evaluate our experience with
      ultrasound-guided bipolar diathermy forceps for cord occlusion in complicated
      monochorionic twin pregnancies. STUDY DESIGN: Seventeen consecutive cases were
      included: 9 cases were twin-to-twin transfusion syndrome; 2 cases were twin
      reversed arterial perfusion syndrome, and 6 cases were discordant for fetal
      abnormality. Bipolar diathermy was performed under local anesthetic with the use
      of 3-mm forceps with ultrasound guidance. RESULTS: Cord occlusion was
      successfully accomplished in all cases between 18 and 27 weeks' gestation. There
      were 2 deaths of the co-twin within 12 hours; 1 death was due to cord hemorrhage,
      and 1 death was unexplained. One neonatal death occurred after delivery at 27
      weeks, and 1 woman with twin-to-twin transfusion syndrome elected termination of
      pregnancy when hydrocephaly was diagnosed 7 days after the procedure (probably
      related to the underlying pathologic condition). All other co-twins are alive and
      well, although 2 pregnancies were complicated by preterm delivery and premature
      rupture of membranes before 30 weeks' gestation. CONCLUSION: Bipolar diathermy is
      an effective procedure for cord occlusion, although it still has significant
      morbidity and mortality rates.

PMID- 11568802
TI  - Perinatal morbidity and mortality rates in severe twin-twin transfusion syndrome:
      results of the International Amnioreduction Registry.
AB  - OBJECTIVE: Serial aggressive amnioreduction is the most widely used therapy for
      pregnancies that are complicated by twin-twin transfusion syndrome. Survival
      rates reported with this therapy are 33% to 83%, the wide range attributable to
      the small number of patients in these case series. Similarly, data on morbidity
      in survivors are imprecise. We instituted the international twin-twin transfusion
      syndrome registry to determine the perinatal survival and morbidity rates and the
      factors that influence perinatal outcome in patients with twin-twin transfusion
      syndrome who were treated with serial aggressive amnioreduction from 1990 to
      1998. STUDY DESIGN: A total of 223 sets of twins who were diagnosed with twin
      twin transfusion syndrome before 28 weeks' gestation from 20 fetal medicine
      referral centers were analyzed, with follow-up data until 4 weeks after birth.
      RESULTS: Three hundred forty-six twins (78%; 182 recipients and 164 donors) were
      born alive. Two hundred sixty-six twins (60%; 144 recipients and 122 donors) were
      alive 4 weeks after birth. Both fetuses survived to 4 weeks in 108 pregnancies
      (48.4%), whereas, at least 1 fetus survived in 158 pregnancies (70.8%). The
      interval between the last amnioreduction and delivery ranged from zero to 138
      days (median, 17.5 days). In the infants who survived to 4 weeks after birth,
      abnormalities on neonatal cranial scan were diagnosed in 24% of recipients and in
      25% of donors. Logistic regression analysis indicated that the survival rate was
      significantly related to gestational age at diagnosis, presence of end-diastolic
      blood flow in the umbilical artery velocity waveforms, presence of hydrops, mean
      volume of amniotic fluid removed per week, larger birth weight, and gestational
      age at delivery. The hemoglobin level difference at birth was the only
      significant parameter to predict abnormal cranial ultrasonography in newborns.
      CONCLUSION: These data document perinatal survival and neonatal morbidity rates
      in severe twin-twin transfusion syndrome that were treated by serial aggressive
      amnioreduction. Outcome was influenced by several perinatal risk factors, which
      may be used to counsel patients before and during therapy.

PMID- 11568803
TI  - A high-throughput study of gene expression in preterm labor with a subtractive
      microarray approach.
AB  - OBJECTIVE: We propose that elucidation of the pathophysiology of preterm labor
      can be achieved with genome-scale analyses of differential gene expression. STUDY
      DESIGN: CD-1 mice on day 14.5 of a 19- to 20-day gestation were assigned to one
      of 4 treatment groups modeling different clinical conditions (n = 5 per group):
      group A, infection with labor (intrauterine injection of 10(10) heat-killed
      Escherichia coli, which causes delivery within an average of 20 hours); group B,
      infection without labor (intrauterine injection of 10(7) heat-killed E coli,
      which leads to normal delivery at term); group C, labor without infection
      (ovariectomy, which causes delivery within an average of 27 hours); and group D,
      no infection and no labor (intrauterine injection of vehicle). Total pooled
      myometrial RNA was prepared 3.5 hours after surgery for groups A, B, and D and 5
      hours after surgery for group C. The relative expression of 4963 genes was
      assayed in these pools by using DNA microarrays. Transcripts specifically
      involved in infection-induced labor were identified by subtracting from the list
      of differentially regulated genes in group A those with common expression in
      groups B and C. RESULTS: In group A 68 differentially expressed transcripts
      (>or=2-fold upregulation or downregulation) were identified. Among these are 39
      characterized genes. Fourteen (45%) are involved in inflammatory responses, 7
      (18%) are involved in growth-differentiation-oncogenesis, and 3 (8%) are involved
      in apoptosis. Subtraction identified 13 gene products most likely to be important
      for bacterially induced labor, as opposed to labor without infection or bacterial
      exposure without labor. CONCLUSION: This study demonstrates the potential of the
      subtractive DNA microarray technique to identify transcripts important
      specifically for bacterially induced preterm labor.

PMID- 11568804
TI  - Effect of preeclampsia on umbilical cord blood hematopoietic progenitor-stem
      cells.
AB  - OBJECTIVE: The aim of the present study was to determine the influence of
      preeclampsia on cord blood hematopoietic progenitor-stem cells obtained at
      delivery because cord blood is increasingly used clinically for stem cell
      retrieval as an alternative to bone marrow. STUDY DESIGN: Umbilical cord blood
      was collected from patients fulfilling the criteria for preeclampsia and from
      gestational age- and birth weight-matched control subjects at delivery
      (patient/control subjects ratio, 1:2). Cord blood volume and nucleated cell
      content were measured, and the number of hematopoietic progenitor-stem cells was
      determined by means of fluorescence-activated cell sorting with the CD34(+)
      epitope and by means of colony assays with different hematopoietic growth
      factors. In addition, the expression of adhesion molecules by CD34(+) progenitor
      stem cells was examined. RESULTS: In pregnancies affected by preeclampsia, volume
      and nucleated cell and total CD34(+) cell contents in the collected cord blood
      were significantly smaller compared with those of control subjects. Furthermore,
      there was a trend toward a smaller relative number of CD34(+) cells and colony
      forming units per nucleated cell in cord blood samples from preeclamptic
      patients. No difference in the expression of the cell-adhesion molecules
      leukocyte function-associated antigen 1, very late activation antigen 4, and L
      selectin by CD34(+) cells could be found. CONCLUSION: This study shows that
      preeclampsia affects umbilical cord blood volume and nucleated cell and
      progenitor-stem cell numbers obtained at birth.

PMID- 11568805
TI  - Fetoscopic temporary tracheal occlusion by means of detachable balloon for
      congenital diaphragmatic hernia.
AB  - Occlusion of the fetal trachea blocks the egress of fetal lung fluid and
      stimulates the growth of hypoplastic lungs in fetuses with diaphragmatic hernia.
      Accomplishing temporary and reversible occlusion of the fetal trachea has proven
      difficult without invasive fetal surgery. Using simultaneous real-time
      ultrasonography and fetal bronchoscopy through a single uterine port, we placed a
      detachable balloon in the trachea of 2 fetuses with severe diaphragmatic hernia.
      In both fetuses the fetal lung subsequently enlarged, allowing survival after
      birth.

PMID- 11568806
TI  - The role of cephalocentesis in modern obstetrics.
AB  - OBJECTIVE: Destructive procedures to permit vaginal delivery of the fetus with
      hydrocephalus are rarely performed. STUDY DESIGN: We performed intrapartum
      cephalocentesis in 3 cases in which alobar holoprosencephaly was diagnosed in the
      third trimester. RESULTS: All 3 fetuses were stillborn. Two delivered vaginally,
      and one delivered abdominally with a lower uterine incision. CONCLUSIONS: A
      reappraisal of the proper role of cephalocentesis in modern obstetrics is
      offered.

PMID- 11568807
TI  - The impact of prenatal alcohol exposure on frontal cortex development in utero.
AB  - OBJECTIVE: Whether prenatal alcohol exposure was associated with a reduction in
      the frontal cortex was examined. STUDY DESIGN: Pregnant women (n = 167) received
      multiple ultrasonographic assessments. During the assessment, brain structures
      were visualized and measured, including the distance from the posterior margin of
      the cavum to the calvarium, the distance from the posterior margin of the
      thalamus to the calvarium, the transcerebellar diameter, and the biparietal
      diameter. RESULTS: Regression analyses and odds ratios demonstrated that alcohol
      exposure was associated with a reduction in the frontal cortex, but not other
      brain structures. Strikingly, the percent of fetuses with a frontal cortex below
      the 10th percentile increased from 4% for nonexposed fetuses to 23% for heavily
      exposed fetuses. CONCLUSION: There was a relationship between frontal brain size
      and maternal alcohol consumption, suggesting that ultrasonography may be a
      sensitive tool for detecting alcohol-induced changes in the fetal brain.

PMID- 11568808
TI  - Fetal sinus bradycardia and the long QT syndrome.
AB  - OBJECTIVE: Recent evidence in literature shows that the long QT syndrome accounts
      for a fraction of the sudden infant death syndrome. Newborn infants with
      prolongation of the Q-T interval often show sinus bradycardia, which led us to
      test whether children who were diagnosed with long QT syndrome also show sinus
      bradycardia in the cardiotocogram before birth. STUDY DESIGN: We identified 18
      children who were born from singleton pregnancies at or near term in whom long QT
      syndrome (corrected QT interval, >0.440 second) was diagnosed after birth or in
      childhood. Cardiograms during pregnancy and delivery were available from 17 of
      the 18 children. RESULTS: The cardiotocogram showed persistent fetal sinus
      bradycardia (baseline heart rate permanently below 120 beats/min) in 12 of 17
      fetuses (71%) with long QT syndrome. Two fetuses had additional intermittent
      tachyarrhythmias. CONCLUSION: Sinus bradycardia in the cardiotocogram during
      delivery or in pregnancy may indicate long QT syndrome in the fetus. Postnatal
      electrocardiography should be performed in these children to rule out or confirm
      a prolongation of the Q-T interval.

PMID- 11568809
TI  - Immunoglobulin A anti-beta2-glycoprotein antibodies in women who experience
      unexplained recurrent spontaneous abortion and unexplained fetal death.
AB  - OBJECTIVE: Studies in rheumatologic populations suggest that immunoglobulin A
      antiphospholipid antibodies are strongly associated with the clinical
      manifestations of antiphospholipid syndrome. However, the association between
      immunoglobulin A antiphospholipid antibodies and pregnancy loss is uncertain. We
      determined whether immunoglobulin A antiphospholipid antibodies, specifically
      anti-beta(2)-glycoprotein I and anticardiolipin, are associated with the
      obstetric features of antiphospholipid syndrome. STUDY DESIGN: Sera from 4 groups
      of women were studied: (1) 133 women who experienced unexplained recurrent
      spontaneous abortion, (2) 48 women who experienced unexplained fetal death, (3)
      145 healthy fertile control subjects, and (4) 67 women with well-characterized
      antiphospholipid syndrome. Serum immunoglobulin A, immunoglobulin G, and
      immunoglobulin M anti-beta(2)-glycoprotein I and anticardiolipin antibodies were
      determined by enzyme-linked immunoassay. RESULTS: Groups of women who experienced
      unexplained recurrent spontaneous abortion and unexplained fetal death had a
      higher proportion of women who had positive test results for immunoglobulin A
      anti-beta(2)-glycoprotein I antibodies than fertile control subjects (P < .01,
      chi-square test); these subjects also had higher levels of autoantibody (P =
      .001, Kruskal-Wallis). Women who experienced recurrent spontaneous abortion had a
      higher proportion of women with positive test results for immunoglobulin A
      anticardiolipin antibodies compared to fertile control subjects (P < .05, chi
      square test); this group also had higher levels of autoantibody (P = .0065,
      Kruskal-Wallis test). Linear regression analysis showed significant correlation
      between anti-beta(2)-glycoprotein I immunoglobulin A and anti-beta(2)
      glycoprotein I immunoglobulin G (R = .609; P =.0001) and less correlation between
      anticardiolipin immunoglobulin A and anticardiolipin immunoglobulin G (R = .093;
      P = .065). CONCLUSION: Immunoglobulin A anti-beta(2)-glycoprotein I antibodies
      are more common in women who experience unexplained recurrent spontaneous
      abortion and unexplained fetal death whose initial test results are negative for
      lupus anticoagulant and immunoglobulin G anticardiolipin antibodies compared to
      fertile control subjects. Therefore, these antibodies may identify additional
      women with clinical features of antiphospholipid syndrome who are not identified
      through traditional testing. It is unclear whether these antibodies are directly
      pathogenic, a result of the pregnancy losses, or markers for an underlying, yet
      uncharacterized autoimmune disorder.

PMID- 11568810
TI  - A survey of medical students' opinions about complementary and alternative
      medicine.
AB  - OBJECTIVE: We wished to determine third-year medical students' opinions and
      knowledge related to complementary and alternative medicine (CAM) in a school
      with no formal or elective course on the subject. STUDY DESIGN: A questionnaire
      was offered to third-year medical students during their 8-week rotation on
      obstetrics and gynecology. RESULTS: Most students had been exposed to CAM
      therapies, knew that the majority of the American public was using CAM, believed
      that some CAM interventions were useful, and did not believe CAM therapies were a
      threat to public health. Most students had insufficient knowledge or
      understanding of the safety or lack of it for 10 of the more common CAM
      modalities. Most respondents thought these interventions were useful, but would
      not refer the patient nor dissuade her from using them. There were no significant
      differences in responses between men and women or related to the time in the year
      of the clerkship. CONCLUSION: Medical students in this school self-identified an
      interest about the clinical usefulness of 10 CAM modalities, but did not have
      sufficient knowledge about the safety for 10 of the more common CAM modalities.
      Including CAM topics in the medical school curriculum would better prepare
      physicians to respond to patient inquiries about CAM and thereby to fulfill their
      role as patient advocates.

PMID- 11568811
TI  - Assessing fertility in women of advanced reproductive age.
AB  - Reproductive capacity in women declines dramatically beyond the fourth decade of
      life. Oocyte quality seems to be the primary determinant of reproductive
      potential, although age-related uterine changes may also contribute. Underlying
      reasons for reproductive decline in women remain unclear, and both ovarian and
      neuroendocrine mechanisms have been proposed.A number of age-related
      endocrinologic changes precede menopause and predict diminished reproductive
      capacity. Thus, "ovarian reserve" screening may identify patients in whom
      attempts at conventional assisted reproduction is warranted before proceeding
      with ovum donation. Techniques to preserve the maternal genetic contribution to
      offspring (in lieu of egg donation), including germinal vesicle transfer and
      donor ooplasm, are under investigation.

PMID- 11568812
TI  - Fetal pulse oximetry in intrapartum management of nonreassuring fetal heart rate
      patterns.

PMID- 11568813
TI  - Dysmorphogenesis and oxidative stress in diabetic rats.

PMID- 11568814
TI  - Multifetal pregnancy reduction.

PMID- 11568815
TI  - Insulin lispro and the development of proliferative diabetic retinopathy during
      pregnancy.

PMID- 11568816
TI  - De novo adhesions due to dry laparoscopy gas.

PMID- 11568817
TI  - Fetal transmission pulse oximetry: is it accurate?

PMID- 11568818
TI  - PCOS and OCPs?

PMID- 11568819
TI  - Functional divergences of PKC isoforms in the human myometrium?

PMID- 11568820
TI  - Neurobiology of decreased sensitivity to stress as pregnancy advances.

PMID- 11568821
TI  - Detection and quantification of coronary stenosis severity with myocardial
      contrast echocardiography.
AB  - The development of microbubble contrast agents and new imaging modalities now
      allows the assessment of myocardial perfusion during echocardiography. These
      microbubbles are excellent tracers of red blood cell kinetics. Apart from
      providing a spatial assessment of myocardial perfusion, myocardial contrast
      echocardiography (MCE) can also be used to quantify the 2 specific components of
      myocardial blood flow-flow velocity and myocardial blood volume. The method to
      quantify myocardial blood flow velocity is based on rapid destruction of
      microbubbles by ultrasound, and subsequent assessment of the rate of
      replenishment of microbubbles into the myocardial microcirculation within the
      ultrasound beam elevation. Assessment of steady state myocardial video intensity
      (VI) provides a measure of myocardial or capillary blood volume. Perfusion
      defects that develop distal to a stenosis during hyperemia are therefore due to
      capillary derecruitment. We have shown that the degree of derecruitment (and
      therefore the severity of a perfusion defect) is proportional to stenosis
      severity. Because the capillary bed also provides the greatest resistance to
      hyperemic flow, decreases in capillary blood volume distal to a stenosis during
      hyperemia result in increases in microvascular resistance, which is the mechanism
      underlying the progressive decrease in flow reserve in the presence of a
      stenosis. Consequently, both the severity of a perfusion defect and
      quantification of abnormal myocardial blood flow reserve on MCE can be used to
      determine stenosis severity. As imaging methods with MCE continue to be refined,
      the optimal imaging algorithms for clinical practice still need to be determined.
      MCE, however, holds promise as a noninvasive, instantaneous, on-line method for
      the detection and quantification of coronary artery disease.

PMID- 11568822
TI  - Ultrasound, microbubbles, and thrombolysis.
AB  - Although dissolution of thrombus using ultrasound has been attempted for over 25
      years, the clinical use of this technique remains limited. The ability of
      microbubbles to potentiate ultrasound-induced thrombolysis has renewed interest
      in this technique, which recanalizes occluded vessels without the need for
      fibrinolytic therapy. In this article, the potential mechanisms by which
      ultrasound and microbubbles produce thrombus dissolution are explored. In vitro
      and in vivo studies using ultrasound alone and ultrasound in combination with
      microbubbles to cause thrombolysis are reviewed. Potential clinical implications
      of more recent findings are explored.

PMID- 11568823
TI  - Assessment of inflammation with contrast ultrasound.
AB  - Future clinical applications of contrast-enhanced ultrasound will likely expand
      beyond the assessment of microvascular perfusion. One promising direction is the
      development of site-targeted microbubbles that are retained within regions of a
      specific disease process and thereby allow phenotypic characterization of tissue.
      Inflammation is an ideal disease state for targeting with microbubbles because
      the pathophysiologic processes that initiate and support the inflammatory
      response occur within the microcirculation, where microbubbles reside. This
      review describes methods that have been used to direct microbubbles to regions of
      inflammation. These methods rely on either (1) intrinsic properties of albumin or
      lipid microbubbles that promote their attachment to leukocyte adhesion molecules,
      or (2) conjugation of monoclonal antibodies or other ligands to the microbubble
      surface that recognize specific endothelial cell adhesion molecules. This review
      also considers ultrasound imaging methods that may be used to detect microbubbles
      retained within inflamed tissue.

PMID- 11568824
TI  - Pharmacologic conversion of atrial fibrillation: a systematic review of available
      evidence.
AB  - This report reviews the efficacy of currently available antiarrhythmic agents for
      conversion of atrial fibrilation (AF) to normal sinus rhythm (NSR). A systematic
      search of literature in the English language was done on computerized databases,
      such as MEDLINE, EMBASE, and Current Contents, in reference lists, by manual
      searching, and in contact with expert informants. Published studies involving
      humans that described the use of antiarrhythmic therapy for conversion of AF to
      NSR were considered and only studies that examined the use of agents currently
      available in the United States were included. Studies exclusively describing
      antiarrhythmic therapy for conversion of postsurgical AF were excluded. The
      methodology and results of each trial were assessed and attempts were made to
      acquire additional information from investigators when needed. Assessment of
      methodological quality was incorporated into a levels-of-evidence scheme. Eighty
      eight trials were included, of which 34 (39%) included a placebo group (level I
      data). We found in recent-onset AF of less than 7 days, intravenous (i.v.)
      procainamide, high-dose i.v. or high-dose combination i.v. and oral amiodarone,
      oral quinidine, oral flecainide, oral propafenone, and high-dose oral amiodarone
      are more effective than placebo for converting AF to NSR. In recent-onset AF of
      less than 90 days, i.v. ibutilide is more effective than placebo and i.v.
      procainamide. In chronic AF, oral dofetilide converts AF to NSR within 72 hours,
      and oral propafenone and amiodarone are effective after 30 days of therapy. We
      conclude than for conversion of recent-onset AF of less than 7 days, procainamide
      may be considered a preferred i.v. agent and propafenone a preferred oral agent.
      For conversion of recent-onset AF of longer duration (less than 90 days), i.v.
      ibutilide may be considered a preferred agent. For patients with chronic AF and
      left ventricular dysfunction, direct current cardioversion is the preferred
      conversion method. Larger, well-designed randomized controlled trials with
      clinically important endpoints in specific populations of AF patients are needed.

PMID- 11568825
TI  - Comprehensive treatment of burns.

PMID- 11568826
TI  - The value of a new filler material in corrective and cosmetic surgery: DermaLive
      and DermaDeep.
AB  - DermaLive is a long-term wrinkle reduction product including two types of
      components: pure hyaluronic acid, produced in cell culture, and an acrylic
      hydrogel. The product was first marketed in France and the rest of Europe in
      1998. We have over three years of experience with this product. Several studies
      have been conducted simultaneously, mainly in Germany and in France. At present,
      DermaLive is used in the long-term correction of natural or acquired skin
      depressions (caused by aging, trauma) or the creation of volume (lips, sunken
      cheekbones). It provides a worthwhile alternative to good-quality bioresorbable
      materials (pure hyaluronic acid or collagen)--materials that are so resorbable,
      in fact, that most patients are ultimately dissatisfied with the results--and to
      other so-called permanent materials that patients do not tolerate well. Filling
      involving the use of autologous fat transplantations, which yields satisfactory
      results, is not appropriate for ambulatory injection and, therefore, will not be
      examined in detail. The tolerance experienced with DermaLive three years on is,
      at present, considered highly satisfactory. The wrinkle reduction effect obtained
      after the first injection is long-lasting with 60% resorption of the initial
      material. Two or three injections, with an interval of at least three months
      between each, may be required to bring about the reduction of some wrinkles or
      the correction of post-scar depressions. Side effects occurring long after the
      injection are rare (1.2 for 1,000). They appear mainly as palpable nodules
      occurring about six months after injection. They are treated by intralesional
      injection of corticoids. DermaLive and DermaDeep are both filler implants with a
      long-lasting effect designed for corrective and aesthetic surgery. Instruction of
      use and intervals between injection sessions must be respected. After DermaLive
      or DermaDeep injection, injections of pure hyaluronic acid (Juvederm or
      Restylane) for treatment of fine lines and superficial defects yield safe and
      excellent aesthetic results.

PMID- 11568827
TI  - Fat transplantation for soft tissue augmentation in the lower limbs.
AB  - Attempts at fat transplantation in humans began as early as 1893 with Neuber [1]
      and came to the fore again with the introduction of liposuction. In his 1988
      paper, titled "Present Results of Fat Injections," Illouz [2] concluded that
      permanent results were achieved in only 20 to 30% of cases. Numerous other
      authors also reported poor outcomes. The uniform conclusion of almost all the
      authors was that the outcome was the result of the common method they followed,
      that is, injecting fat subcutaneously. However, the poor perfusion of the
      subcutaneous tissue does not appear to be adequate for the timely
      revascularization of adipocytes. Around 1983 Jose Guerrerosantos [3,4]
      successfully injected fat intramuscularly in guinea pigs. Subsequent removal and
      histological examination of the grafts demonstrated revascularization and almost
      complete survival of adipocytes, presumably due to the rich perfusion of the
      muscle.

PMID- 11568828
TI  - The effect of reduction of the peripheral fat content by liposuction-assisted
      lipectomy (SAL) on serum leptin levels in the postoperative period: a prospective
      study.
AB  - The purpose of this study was to investigate the relationship between a decrease
      in the peripheral fat content by suction-assisted lipectomy (SAL) and serum
      leptin levels. Twenty-two healthy females who underwent SAL for aesthetic reasons
      participated in the study. The data included height, weight, dietary habits, and
      leptin levels before surgery and at 1 and 6 weeks postoperatively. The aspirate
      ranged between 1000 and 6000 ml, with an average of 2700 ml. Thirteen patients
      with an aspirate of over 2700 ml all experienced an immediate postoperative
      decrease in appetite which returned gradually by 12 to 17 days postoperatively.
      They lost an average of 7% of the total body weight at 6 weeks. The leptin levels
      1 week postoperatively were significantly lower than the preoperative levels (p <
      0.01); at 6 weeks the decrease in leptin level was not statistically significant.
      In conclusion, a reduction of the peripheral fat content of more than 2700 ml by
      SAL has an immediate effect on leptin levels that lasts at least 1 week and
      correlates with voluntary changes in energy intake.

PMID- 11568829
TI  - Short columella nasolabial complex in aesthetic rhinoplasty.
AB  - Many papers describe different approaches for short columella in cleft lip or
      Negroid noses. Very little has been found in international literature related to
      these aesthetic rhinoplasties. The scarce skin of the columella, the firm union
      between the nasal tip and the lip, due to the hypertrophy of the depressor septi
      nasi muscle, and the low projection of the nasal tip, consequence of the open
      position of the caudal part of the medial crura, are the cause of this problem.
      Therefore, the skin, muscle, and cartilage were treated simultaneously. Herein is
      described a VY composite advanced flap for projecting the tip, suturing both
      divergent medial crura together and adding the skin and muscle tissues of the lip
      to the columella. With this flap the tip was projected, the columella was
      narrowed, the nasolabial angle improved, and the upper lip elongated. Good
      results could be achieved without using any other cartilage graft or silastic
      strut. Standard rhinoplasty and septumplasty could be combined with this
      technique. Inconspicuous scars were observed.

PMID- 11568830
TI  - Nasal reconstruction after epithelioma.
AB  - In this paper we present our procedure for the treatment, histopathological
      diagnosis, and resection of skin cancer in the nasal pyramid and its subsequent
      reconstruction. Because we are dealing with the most important anatomical feature
      of the face our goal is an aesthetic reconstruction [2,4] according to the
      anatomical subunits criterion of Burget [3]. First, a histopathological diagnosis
      is made to determine the nature of the tumor. Then, we proceed with the resection
      according to the Mohs Micrographic Surgery [1,5,7]. Then we begin with the first
      step of the nasal reconstruction.

PMID- 11568831
TI  - PVP breast implants after two years: initial results of a prospective study.
AB  - A prospective study of a new mammary prosthesis with PVP-based gel as filling
      material was carried out. Scheduled follow-ups were planned at 3, 6, 12, and 24
      months post-implantation to assess all complications, Baker scores, and the
      patient's, and the physician's global assessment of each implant. PVP-filled
      implants were used in 95 breasts for augmentation (60%) or reconstruction (40%).
      Sixty-nine percent of all patients underwent a primary procedure, 19% had a
      history of severe capsular fibrosis. During follow-up, a hematoma was observed in
      2% and a seroma in 5%. Leakage occurred in 3% (one iatrogenic and two cases of
      unknown reason), a Baker 3 in 6% (12 months). No volume increase of the implants
      occurred. The probability that a patient would be complication-free at 24 months
      was 0.86. Physician's and patient's satisfaction rating after 12 months remained
      high without any time effect (physician very good/good 63%, patient 75%).
      According to our current experiences, the PVP-filled implants are a remarkable
      alternative with an improved viscosity and enhanced x-ray transmission, compared
      to saline filled implants.

PMID- 11568832
TI  - Mammographic findings following reduction mammoplasty.
AB  - Breast reduction mammoplasty is becoming an increasingly common procedure. A
      baseline mammogram is recommended after 35 years of age as the most effective
      method for detection of small breast cancers. A prospective study was conducted
      for the evaluation of the mammographic findings after reduction mammoplasty.
      During the last 7 years, 113 patients over 35 years of age underwent bilateral
      reduction mammoplasty. All patients had a preoperative mammogram. A new mammogram
      was obtained at 6 and 18 months after the procedure. All films were reviewed by
      the same two radiologists. Breast reduction was performed with the vertical
      bipedicle flap technique (McKissock) and the inferior pedicle technique. There
      were no apparent differences in the findings between the two methods. Most common
      findings were parenchymal redistribution in 102 (90.2%) and elevation of the
      nipple in 96 (84.9%), produced by a shift of the breast tissue to a lower
      position. Calcifications were seen in 29 (25.6%), and "oil cysts" in 22 (19.4%),
      caused by localized fat necrosis. A retroareolar fibrotic band was found in 23
      (20.3%), from the transposed flap. Areolar thickening was observed in six (5.3%),
      and skin thickening in only two (1.7%), from scar tissue. Mammographic findings
      after reduction mammoplasty are predictable, thus preventing unnecessary biopsies
      and making the diagnosis of lesions unrelated to the procedure easier. All
      patients over 35 years of age should have a preoperative and a postoperative
      mammogram for future reference.

PMID- 11568833
TI  - Unsatisfactory results of periareolar mastopexy with or without augmentation and
      reduction mammoplasty: enlarged areola with flattened nipple.
AB  - A method of repair is described for correction of abnormally enlarged nipple
      areola complex following both periareolar mastopexy and pregnancy. Although
      during periolar mastopexy or reduction mammoplasty regular subcuticular dermal
      sutures may control the enlargement of nipple-areola complexes initially, the
      periareolar scar becomes hypertrophic and areolar spreading occurs to some
      extent. Periareolar mastopexy techniques are indeed advisable only for minimal
      hypertrophies or ptosis of the breast, especially for areolar asymmetry, if an
      acceptable, normal-size areola is expected. The authors believe that in periolar
      mastopexy or reduction mammoplasty cases resulting in enlarged nipple-areola
      complexes, the size of the areola can also be corrected by reduction mammoplasty
      or mastopexy using vertical bipedicle techniques. Although surgery results in an
      inverted T incision, the shape of the breast is more acceptable and the size of
      the areola does not enlarge with time.

PMID- 11568834
TI  - Postoperative compression after breast augmentation.
AB  - In a randomized study of 130 patients undergoing breast augmentation,
      postoperative compression did not reduce the frequency of postoperative bruising
      or hematoma formation, and 37.5% of the 64 patients having compression had
      complaints regarding their use. Postoperative compression is of no value after
      breast augmentation.

PMID- 11568835
TI  - Breast augmentation with fresh-frozen homologous fat grafts.
AB  - The purpose of this report is to present a patient who underwent breast
      augmentation with fresh-frozen fat homografts in Russia 10 years ago, despite the
      publication of major complications following this procedure.

PMID- 11568836
TI  - Upper eyelid mycobacterial infection following Oriental blepharoplasty in a
      pulmonary tuberculosis patient.
AB  - Bilateral upper blepharoplasty for the Oriental eyelid was performed in a 20-year
      old female on antituberculous therapy for 3 months. The postoperative course was
      smooth and the patient was back to normal life. But unfortunately, at 3 months
      after the upper blepharoplasty, a spherical tumescence and red granuloma
      developed over the right upper eyelid. The granuloma was resected, and on
      pathological examination the specimen revealed epitheloid granuloma with
      Langhan's giant cells and a few acid-fast positive bacilli. The clinical events
      and pathological findings were suggestive of Mycobacterium tuberculosis rather
      than Mycobacterium chelonei as the possible cause of infection. Thus the patient
      was advised to continue antituberculous therapy and no antibiotic was prescribed.
      The eyelid swelling resolved gradually and was completely normal at the end of
      antituberculous therapy. Though it has been suggested that aesthetic surgery can
      be performed safely 3 months after antituberculous therapy in a patient with
      pulmonary tuberculosis, the remote risk of such a complication is always a
      possibility.

PMID- 11568837
TI  - Clinical facial photography in a small office: lighting equipment and technique.
AB  - The taking of clinical photographs, to record and to utilize during surgery, is
      an essential aspect of activity in every professional office or department of
      facial surgery. To obtain the best quality and consistency of results, many
      suggest the use of a professional lighting system composed of two or more flash
      units. An entire room, or a large part of it, should be permanently reserved for
      this use. In the last five years, I have developed and standardized a technique
      for taking facial photography, utilizing a single flash unit (monolight) in a
      small area that, after photographing, is cleared to allow space for other
      activities. A remarkable effort was dedicated to make the procedure easier, to
      save time, to reduce cost, and to make it possible to take a complete set of
      shots without the aid of an assistant.

PMID- 11568838
TI  - Specific requirements for preoperative and postoperative photos used in
      publication.
AB  - In this paper, eight variables in clinical photography are discussed. It is
      important that the photographs taken before and after a procedure be as similar
      as possible in order to accurately reflect the results. The variables that can
      have a big impact on photographs are: the room in which the photographs are
      taken, the camera used, the type of film used, the distance of the photographer
      from the patient, the photographer him or herself, the light source and location,
      the film development process, and when the postoperative photographs are taken.

PMID- 11568839
TI  - A river might run through it again: criteria for consideration of dam removal and
      interim lessons from California.
AB  - Resource managers are increasingly being challenged by stakeholder groups to
      consider dam removal as a policy option and as a tool for watershed management.
      As more dam owners face high maintenance costs, and rivers as spawning grounds
      for anadromous fish become increasingly valuable, dam removal may provide the
      greatest net benefit to society. This article reviews the impact of Endangered
      Species Act listings for anadromous fish and recent shifts in the Federal Energy
      Regulatory Commission's hydropower benefit-costs analysis and discusses their
      implications for dam removal in California. We propose evaluative criteria for
      consideration of dam removal and apply them to two case studies: the Daguerre and
      Englebright Dams on the Yuba River and the Scott and Van Horne Dams on the South
      Eel River, California.

PMID- 11568840
TI  - Toward quantifying water pollution abatement in response to installing buffers on
      crop land.
AB  - The scientific research literature is reviewed (i) for evidence of how much
      reduction in nonpoint source pollution can be achieved by installing buffers on
      crop land, (ii) to summarize important factors that can affect this response, and
      (iii) to identify remaining major information gaps that limit our ability to make
      probable estimates. This review is intended to clarify the current scientific
      foundation of the USDA and similar buffer programs designed in part for water
      pollution abatement and to highlight important research needs. At this time,
      research reports are lacking that quantify a change in pollutant amounts
      (concentration and/or load) in streams or lakes in response to converting
      portions of cropped land to buffers. Most evidence that such a change should
      occur is indirect, coming from site-scale studies of individual functions of
      buffers that act to retain pollutants from runoff: (1) reduce surface runoff from
      fields, (2) filter surface runoff from fields, (3) filter groundwater runoff from
      fields, (4) reduce bank erosion, and (5) filter stream water. The term filter is
      used here to encompass the range of specific processes that act to reduce
      pollutant amounts in runoff flow. A consensus of experimental research on
      functions of buffers clearly shows that they can substantially limit sediment
      runoff from fields, retain sediment and sediment-bound pollutants from surface
      runoff, and remove nitrate N from groundwater runoff. Less certain is the
      magnitude of these functions compared to the cultivated crop condition that
      buffers would replace within the context of buffer installation programs. Other
      evidence suggests that buffer installation can substantially reduce bank erosion
      sources of sediment under certain circumstances. Studies have yet to address the
      degree to which buffer installation can enhance channel processes that remove
      pollutants from stream flow. Mathematical models offer an alternative way to
      develop estimates for water quality changes in response to buffer installation.
      Numerous site conditions and buffer design factors have been identified that can
      determine the magnitude of each buffer function. Accurate models must be able to
      account for and integrate these functions and factors over whole watersheds. At
      this time, only pollutant runoff and surface filtration functions have been
      modeled to this extent. Capability is increasing as research data is produced,
      models become more comprehensive, and new techniques provide means to describe
      variable conditions across watersheds. A great deal of professional judgment is
      still required to extrapolate current knowledge of buffer functions into broadly
      accurate estimates of water pollution abatement in response to buffer
      installation on crop land. Much important research remains to be done to improve
      this capability. The greatest need is to produce direct quantitative evidence of
      this response. Such data would confirm the hypothesis and enable direct testing
      of watershed-scale prediction models as they become available. Further study of
      individual pollution control functions is also needed, particularly to generate
      comparative evidence for how much they can be manipulated through buffer
      installation and management.

PMID- 11568841
TI  - Evolving policies to regulate pollution from animal feeding operations.
AB  - Due to concentrations of animals at large facilities, animal feeding operations
      (AFOs) have emerged as a major potential source of water pollution. The federal
      government regulates concentrated animal feeding operations under its point
      source pollution permitting regulations. A major determinant of whether an
      operation must apply for a permit is the number of animals at an individual lot
      or facility. This paper examines federal mandatory controls and voluntary
      guidelines that seek to reduce contaminant pollution from AFOs. Land treatment
      practices are delineated due to their importance in reducing the injurious by
      products of agricultural production. An evaluation of proposed revisions to
      federal regulations on confined animal feeding operations suggests they diverge
      from their goal of controlling water pollution. Federal regulations focus on the
      size of operation and amount of manure governed by the permitting process to the
      exclusion of other criteria related to the impairment of water quality. Given the
      uncertainties about the amount of pollution from AFOs, lack of enforcement of
      existing regulations, localization of problems, and possible alternatives for
      addressing the pollution, more demanding federal regulations may not form an
      appropriate response.

PMID- 11568842
TI  - Land-use suitability analysis in the United States: historical development and
      promising technological achievements.
AB  - Various methods of spatial analysis are commonly used in land-use plans and site
      selection studies. A historical overview and discussion of contemporary
      developments of land-use suitability analysis are presented. The paper begins
      with an exploration into the early 20th century with the infancy of documented
      applications of the technique. The article then travels through the 20th century,
      documenting significant milestones. Concluding with present explorations of
      advanced technologies such as neural computing and evolutionary programming, this
      work is meant to serve as a foundation for literature review and a premise for
      the exploration of new advancements as we enter into the 21st century.

PMID- 11568843
TI  - Plains cottonwood's last stand: can it survive invasion of Russian olive onto the
      Milk River, Montana floodplain?
AB  - Russian olive (Elaeagnus angustifolia L.) was introduced in 1950 onto one site on
      the Milk River floodplain, northern Montana, 10 km downstream from the
      Canada/United States border. To analyze dispersal of Russian olive from the point
      source between 1950 and 1999, we compared distribution, numbers, size structure,
      and mortality of Russian olive and plains cottonwood (Populus deltoides Marsh:)
      on an unregulated reach of the Milk River floodplain in southeastern Alberta and
      north-central Montana. Within 50 years, Russian olive in this reach has moved
      upriver into Alberta and downriver to the Fresno Reservoir. It is now present on
      69 of the 74 meander lobes sampled, comprising 34%, 62%, and 61% of all Russian
      olive and plains cottonwood seedlings, saplings, and trees, respectively. On some
      meander lobes, Russian olive has colonized similar elevations on the floodplain
      as plains cottonwood and is oriented in rows paralleling the river channel,
      suggesting that recruitment may be related to river processes. Breakup ice had
      killed 400 Russian olive saplings and trees and damaged >1000 others on 30 of the
      meander lobes in 1996. Nevertheless, Russian olive now outnumbers cottonwood on
      many sites on the Milk River floodplain because its seeds can be dispersed by
      wildlife (particularly birds) and probably by flood water and ice rafts; seeds
      are viable for up to 3 years and germination can take place on bare and well
      vegetated soils; and saplings and trees are less palatable to livestock and
      beaver than plains cottonwood. Without control, Russian olive could be locally
      dominant on the Milk River floodplain in all age classes within 10 years and
      replace plains cottonwood within this century.

PMID- 11568844
TI  - A riparian wildlife habitat evaluation scheme developed using GIS.
AB  - To evaluate riparian habitat for wildlife, we used a geographic information
      system (GIS) that prioritized individual streams (for acquisition or management)
      by habitat ranking. We demonstrate this methodology for the Vermilion River basin
      in east-central Illinois, USA. Three data sets were used to evaluate land cover
      encompassing 300 m on either side of the streams: (1) the US Geological Survey's
      land use and land cover information (LUDA), (2) land cover manually digitized
      from the National High Altitude Photography (NHAP) program, and (3) Landsat
      Thematic Mapper (TM) data classified into land cover. Each of 30 tributaries in
      the study area was ranked for habitat according to the data contained in each
      data set, and results were compared. Habitat ranking schemes were devised and
      analysis performed for three species guilds: forest, grassland, and mixed
      successional species. TM and NHAP each differentiated habitat scores (for forest,
      grassland, and mixed successional guilds) among tributaries in a similar and
      suitable way, while LUDA was not suitable, due to the coarse resolution of the
      data. Overall, it was shown that the methodology is suitable to rank streams
      based on riparian habitat quality. Even though more work is needed to test and
      verify the method, the project has shown the potential for such techniques to
      assist in evaluating, tracking, and improving the management of riparian wildlife
      resources. The method can easily be applied over large areas such as states if TM
      based land cover and stream data are available.

PMID- 11568845
TI  - Evaluation of groundwater and soil pollution in a landfill area using electrical
      resistivity imaging survey.
AB  - Landfills are sources of groundwater and soil pollution due to the production of
      leachate and its migration through refuse. This study was conducted in order to
      determine the extent of groundwater and soil pollution within and around the
      landfill of Seri Petaling located in the State of Selangor, Malaysia. The
      condition of nearby surface water was also determined. An electrical resistivity
      imaging survey was used to investigate the leachate production within the
      landfill. Groundwater geochemistry was carried out and chemical analysis of water
      samples was conducted upstream and downstream of the landfill. Surface water was
      also analyzed in order to determine its quality. Soil chemical analysis was
      performed on soil samples taken from different locations within and around the
      landfill in the vadose zone (unsaturated zone) and below the water table (in the
      soil saturated zone). The resistivity image along line L-L1 indicated the
      presence of large zones of decomposed waste bodies saturated with highly
      conducting leachate. Analysis of trace elements indicated their presence in very
      low concentrations and did not reflect any sign of heavy metal pollution of
      ground and surface water or of soil. Major ions represented by Na, K, and Cl were
      found in anomalous concentrations in the groundwater of the downstream bore hole,
      where they are 99.1%, 99.2%, and 99.4%, respectively, higher compared to the
      upstream bore hole. Electrical conductivity (EC) was also found in anomalous
      concentration downstream. Ca and Mg ions represent the water hardness (which is
      comparatively high downstream). There is a general trend of pollution towards the
      downstream area. Sulfates (SO4) and nitrates (NO3) are found in the area in low
      concentrations, even below the WHO standards for drinking water, but are
      significantly higher in the surface water compared to the groundwater. Phosphate
      (PO4) and nitrite (NO2), although present in low levels, are significantly higher
      at the downstream. There is no significant difference in the amount of fluoride
      (F) in the different locations. In the soil vadose zone, heavy metals were found
      to be in their typical normal ranges and within the background concentrations.
      Soil exchangeable bases were significantly higher in the soil saturated zone
      compared to the vadose zone, and no significant difference was obtained in the
      levels of inorganic pollutants. With the exception of Cd, the concentration
      ranges of all trace elements (Cu, Zn, Cr, Pb, and Ni) of Seri Petaling landfill
      soils were below the upper limits of baseline concentrations published from
      different sources.

PMID- 11568846
TI  - Perceptions, preferences, and reactions of local inhabitants in Vikos-Aoos
      National Park, Greece.
AB  - Local inhabitants' perceptions, preferences, and reactions were investigated in
      Vikos-Aoos National Park, 25 years after its designation. Knowledge of aims of
      the park and source of information about them, necessity for infrastructure,
      reactions to certain policies, and effectiveness of administration and management
      scheme were studied by means of a questionnaire survey. Personal interviews were
      performed by systematic sampling, which resulted in 203 cases for analysis. Most
      respondents said that they had knowledge of the aims of the national park, and
      this was positively associated with education; protection of flora and fauna was
      identified by most as the main aim, and the management authority (the Forest
      Service) ranked first in order as source of information. Tourism development of
      the area was seen as a positive change, and recreation facilities and improvement
      in accessibility were considered of high priority for development. The
      investigation into peoples' reactions to several possible alternative management
      policies revealed willingness to accept certain restrictions on their
      agricultural use of the land. A policy of non-intensive agriculture with
      compensation for loss of income, if the ecosystems of the park were in danger,
      seems the most acceptable. Long-term leasing of farms by the Forest Service was
      another policy with a high degree of acceptance, especially for certain
      occupational groups; those working in the secondary and tertiary sectors of
      economy would accept such a policy more easily than those working in the primary
      sector. Finally, a very large majority of the respondents expressed a preference
      for a new administration and management scheme with the participation of local
      communities in the decision-making process.

PMID- 11568847
TI  - Energy analysis of nonmarket values of the Mississippi Delta.
AB  - An energy analysis was used to estimate nonmarket values under various land cover
      scenarios in the Mississippi Delta. Land loss since 1900 has led to a decline in
      nonmarket values from $3.1 billion/year in 1900 to $2.5 billion in 1990,
      resulting in a total loss of $29.4 billion. This loss is concentrated in the
      Barataria-Terrebonne basins, where nonmarket value has dropped from $1.6
      billion/year in 1956 to $1.3 billion/year in 1988. Although values are projected
      to increase in the Atchafalaya basin (from $723 million/year in 1988 to $756
      million/year in 2058), total nonmarket value for the Louisiana coast is projected
      to decrease to $2.1 billion/year under currently approved levels of restoration.

PMID- 11568848
TI  - Woody debris in north Iberian streams: influence of geomorphology, vegetation,
      and management.
AB  - The effect of stream geomorphology, maturity, and management of riparian forests
      on abundance, role, and mobility of wood was evaluated in 20 contrasting reaches
      in the Aguera stream catchment (northern Iberian Peninsula). During 1 year the
      volume of woody debris exceeding 1 cm in diameter was measured in all reaches.
      All large woody debris (phi > 5 cm) pieces were tagged, their positions mapped,
      and their subsequent changes noted. Volume of woody debris was in general low and
      ranged from 40 to 22,000 cm3 m-2; the abundance of debris dams ranged from 0 to
      5.5 per 100 m of channel. Wood was especially rare and unstable in downstream
      reaches, or under harvested forests (both natural or plantations). Results stress
      that woody debris in north Iberian streams has been severely reduced by forestry
      and log removal. Because of the important influence of woody debris on structure
      and function of stream systems, this reduction has likely impacted stream
      communities. Therefore, efforts to restore north Iberian streams should include
      in-channel and riparian management practices that promote greater abundance and
      stability of large woody debris whenever possible.

PMID- 11568849
TI  - Evaluation of use of a single intravaginal swab to detect multiple sexually
      transmitted infections in active-duty military women.
AB  - The accuracy and suitability of use of a single intravaginal swab (SIS) for
      polymerase chain reaction detection of Neisseria gonorrhoeae, Chlamydia
      trachomatis, Trichomonas vaginalis, and human papillomavirus infection was
      assessed in a cross-sectional study of 841 active-duty military women. The SIS,
      compared with standard diagnostic tests, allowed detection of more gonorrhea,
      more chlamydial infection, and more trichomoniasis. Sensitivity and specificity
      of SIS detection compared with adjudicated true-positive diagnoses were 95.8% and
      97.8%, respectively, for gonorrhea, 94.6% and 99.3% for chlamydial infection, and
      92.2% and 98.2% for trichomonal infection. Results with SISs were comparable to
      those with cervical swabs tested for human papillomavirus. Assay of clinician
      collected and self-collected SISs yielded prevalences similar to those of
      standard diagnostic tests for all sexually transmitted infections. Therefore, the
      use of SISs is acceptable for the simultaneous diagnosis of multiple sexually
      transmitted infections and has potential for use as a self-administered
      diagnostic tool with widespread applicability among women.

PMID- 11568850
TI  - Nosocomial aspergillosis is waterborne.
AB  - Nosocomial invasive aspergillosis can cause life-threatening infections among
      immunosuppressed patients and is thought to be primarily airborne. Despite the
      use of appropriate hospital air filtration systems, however, the incidence of
      this infection continues to increase. In this article, we present our hypothesis,
      which is that nosocomial aspergillosis can be airborne from a water source in the
      hospital. If confirmed by ongoing studies, this hypothesis would imply a change
      in the current infection control practices aimed at preventing nosocomial
      aspergillosis.

PMID- 11568851
TI  - The microbiology of postoperative peritonitis.
AB  - Postoperative peritonitis carries a higher risk of complications and mortality
      than does community-acquired disease. Little, however, is known about the
      specific microbiology of this condition. To gain insight into this problem, the
      microbiological findings of 67 patients with postoperative peritonitis were
      compared with those of 68 patients with community-acquired peritonitis. In a
      comparison of postoperative peritonitis with community-acquired disease, the
      number of isolates of enterococci (23 versus 6) and Enterobacter species (13
      versus 4) were increased and the number of isolates of Escherichia coli (21
      versus 42) were reduced. Antibiotic therapy before reintervention increased the
      number of resistant organisms at relaparotomy (33% versus 8%). The in vitro
      efficacy of the primary antibiotic or combination of drugs did not affect
      mortality rates (40% versus 38% after effective and ineffective treatment,
      respectively). Thus, the microbiology of postoperative peritonitis differs
      significantly from that of community-acquired disease, and specific antibiotic
      therapy is required, despite the doubtful impact on survival.

PMID- 11568852
TI  - Distribution of Pneumocystis carinii f. sp. hominis types in the lung of a child
      dying of Pneumocystis pneumonia.
AB  - Pneumocystis f. sp. hominis causes pneumonia in immunocompromised persons. In
      order to determine the types and distribution of P. carinii organisms within a
      single human lung, multiple samples were obtained from the lung of a child who
      died of P. carinii pneumonia. P. carinii DNA was detected in all of the samples
      and 2 different genotypes of P. carinii were identified, with uneven distribution
      in the lung, demonstrating that infection of the human lung is not necessarily
      clonal, and that different P. carinii genotypes may predominate in different
      areas of the lung.

PMID- 11568853
TI  - Infection of the skin caused by Corynebacterium ulcerans and mimicking classical
      cutaneous diphtheria.
AB  - Extrapharyngeal infections caused by Corynebacterium ulcerans have rarely been
      reported previously, and diphtheria toxin production has usually not been
      addressed. This case demonstrates that strains of C. ulcerans that produce
      diphtheria toxin can cause infections of the skin that completely mimic typical
      cutaneous diphtheria, thereby potentially providing a source of bacteria capable
      of causing life-threatening diseases in the patient's environment. Therefore, it
      is recommended to screen wound swabs for coryneform bacteria, identify all
      isolates, carefully assess possible toxin production, and send questionable
      strains to a specialist or a reference laboratory.

PMID- 11568854
TI  - Counterpoint: invasive aspergillosis and the environment--rethinking our approach
      to prevention.
AB  - Preventive measures are important in the control of invasive aspergillosis (IA)
      because diagnosis is difficult and the outcome of treatment is poor. If effective
      strategies are to be devised, it will be essential to have a clearer
      understanding of the sources and routes of transmission of Aspergillus species.
      Nosocomial outbreaks of IA highlight the fact that Aspergillus spores are common
      in the hospital environment. However, in general, such outbreaks are uncommon.
      Most cases of IA are sporadic in nature, and many of them are now being acquired
      outside of the hospital setting. Housing patients in high-energy particulate air
      filtered hospital rooms helps prevent IA, but it is feasible and cost-effective
      only for the highest-risk groups and for limited periods. Control measures, which
      are designed to protect patients from exposure to spores outside the hospital,
      are even more difficult. Nevertheless, now that high-risk patients are spending
      more time outside of the hospital, the cost benefits of antifungal prophylaxis
      and other preventive measures require careful evaluation.

PMID- 11568855
TI  - Legionella pneumophila pneumonia in a newborn after water birth: a new mode of
      transmission.
AB  - We report a case of Legionella pneumophila pneumonia in a 7-day old neonate.
      Because the hospital water, and particularly the pool water for water birthing,
      was contaminated by L. pneumophila serogroup 1, the newborn was infected
      following prolonged delivery in contaminated water, perhaps by aspiration. This
      is the first case of nosocomial Legionella pneumonia in neonate after water
      birth.

PMID- 11568856
TI  - Pharmacokinetic interactions of nevirapine and methadone and guidelines for use
      of nevirapine to treat injection drug users.
AB  - Administration of nevirapine to HIV-infected injection drug users who also
      receive methadone results in a significant reduction in methadone exposure after
      7-10 days of therapy. Many patients require an increase in methadone dose to
      counteract this effect.

PMID- 11568857
TI  - Infections with Ehrlichia chaffeensis and Ehrlichia ewingii in persons coinfected
      with human immunodeficiency virus.
AB  - The clinical course and laboratory evaluation of 21 patients coinfected with
      human immunodeficiency virus (HIV) and Ehrlichia chaffeensis or Ehrlichia ewingii
      are reviewed and summarized, including 13 cases of ehrlichiosis caused by E.
      chaffeensis, 4 caused by E. ewingii, and 4 caused by either E. chaffeensis or E.
      ewingii. Twenty patients were male, and the median CD4(+) T lymphocyte count was
      137 cells/microL. Exposures to infecting ticks were linked to recreational
      pursuits, occupations, and peridomestic activities. For 8 patients, a diagnosis
      of ehrlichiosis was not considered until > or =4 days after presentation. Severe
      manifestations occurred more frequently among patients infected with E.
      chaffeensis than they did among patients infected with E. ewingii, and all 6
      deaths were caused by E. chaffeensis. Ehrlichiosis may be a life-threatening
      illness in HIV-infected persons, and the influence of multiple factors, including
      recent changes in the epidemiology and medical management of HIV infection, may
      increase the frequency with which ehrlichioses occur in this patient cohort.

PMID- 11568858
TI  - Risk Factors for Candida tropicalis fungemia in patients with cancer.
AB  - The risk factors for and presentation of Candida tropicalis fungemia, in
      comparison with those of Candida albicans, have been incompletely characterized.
      We compared 43 cases of C. tropicalis fungemia with 148 cases of C. albicans
      fungemia. In univariate analysis, patients with C. tropicalis fungemia were more
      likely to have leukemia (P=.0006), prolonged neutropenia (P=.03), and a positive
      blood culture for more days (P=.02). The 2 groups did not differ with regard to
      baseline Acute Physiology and Chronic Health Evaluation (APACHE) II score,
      frequency of catheter-associated fungemia, or response to antifungals. In
      multivariate analysis, patients with C. tropicalis fungemia were more likely to
      have leukemia (P=.02), previous neutropenia (P=.002), and a longer stay in the
      intensive care unit during the infectious episode (P=.01). Also, the response of
      the breakthrough C. tropicalis fungemia was lower (P=.05). In conclusion, the
      host determinants associated with susceptibility to C. tropicalis are leukemia
      and prolonged neutropenia.

PMID- 11568859
TI  - Genetic population structure of coagulase-negative staphylococci associated with
      carriage and disease in preterm infants.
AB  - Coagulase-negative staphylococci (CoNS) are a leading cause of sepsis in the
      neonatal intensive care unit (NICU) setting. To evaluate the hypothesis that
      isolates of CoNS associated with disease belong to hypervirulent clones, as
      opposed to being drawn randomly from the neonatal unit carriage flora, we
      conducted a prospective, case-controlled study in a busy NICU. Using pulsed-field
      gel electrophoresis (PFGE), we compared the population structures of CoNS
      isolates associated with bacteremia with isolates from the skin of healthy and
      infected neonates and with blood culture contaminants. Endemic clones of CoNS
      were identified, but there was no difference in the distribution of the 6 species
      or 73 PFGE types between the carriage and disease isolate groups; this suggests
      that hypervirulent clones with an enhanced ability to cause disease were not
      present in this NICU setting.

PMID- 11568860
TI  - Eosinophilic meningitis due to Angiostrongylus cantonensis in a returned
      traveler: case report and review of the literature.
AB  - Angiostrongylus cantonensis, the rat lungworm, is the principal cause of
      eosinophilic meningitis worldwide, and the increase in world travel and shipborne
      dispersal of infected rat vectors has extended this parasite to regions outside
      of its traditional geographic boundaries. We report a case of eosinophilic
      meningitis due to A. cantonensis in a patient who recently returned from a trip
      in the Pacific.

PMID- 11568861
TI  - [Therapeutic changes beyond the symptoms - effects of inpatient treatment
      according to the Heidelberg Structural Change Scale].
AB  - The question is discussed how changes concerning the patient's ability to
      recognize and obtain insight into dysfunctional relationship patterns, life
      determining conflicts, and structural vulnerability as well as the readiness to
      take on the responsibility for the negative effects caused by these may be
      conceptualized. A model has been developed based on Operationalized Psychodynamic
      Diagnosis (OPD) in which individual problem areas for each patient may be chosen
      from a list of foci. Changes in these foci are evaluated using the Heidelberg
      Structural Change Scale which is presented and discussed in detail. This concept
      is applied to a sample of patients who had been treated in an in-patient setting.
      It is demonstrated that this method of measuring changes can be used reliably.
      Furthermore, the changes registered with the structural change scale correlate on
      an absolute level quite high to the global assessment of outcome through the
      therapeutic team; this correlation is even higher than the correlation between
      symptomatic changes and the global assessments. How this concept may be applied
      in planning, evaluating, and ensuring the quality of psychotherapy is presented
      in conclusion.

PMID- 11568862
TI  - [Causal attribution and personality in psychotherapy patients].
AB  - The present study addressed the relationship between patients' causal
      attributions of their disorders on one hand and their personality traits on the
      other. The investigation was based on the self-reports of 197 psychotherapy
      patients who presented at a university outpatient department for diagnostic
      evaluation. Personality traits were measured using the Giessen-Test (Beckmann et
      al., 1991), causal attributions were assessed by a check list (Faller 1997).
      Intrapsychic causal factors were rated highest; after those, interpersonal and
      social factors followed next, while somatic factors were judged to be least
      important. Psychosocial attributions showed strong correlations with the self
      report of depressed mood in the Giessen-Test. Similar relations were found with
      other personality traits such as low ratings of social resonance, low openness,
      and low social potency. The reported interrelations suggest that psychological
      symptoms, personality and causal atttributions are closely intertwined.

PMID- 11568863
TI  - [Differences between patients classified as "recovered" or "improved" and
      "unchanged" or "deteriorated" in a psychotherapy outcome study].
AB  - The concepts of statistical and clinical significance of pre-post-changes have
      been used to class patients into four groups of therapy outcome: "recovered",
      "improved", "unchanged" and "deteriorated". Aim of this study is to investigate
      the advantages of this classification in comparison to a simple division into
      "successful" and "not successful". 43 patients were examined before and after an
      in-patient psychotherapy and again two years later with several test inventories.
      Therapy outcome was measured by the changes in the Global Severity Index of the
      SCL-90-R. "Recovered" and "improved" patients did only differ in regard to their
      initial symptom severity, but not in regard to the amount of symptom reduction or
      stability of therapy effect. "Deteriorated" patients could reduce their increase
      in symptoms until follow-up. Our results do not indicate a general advantage of
      the classification into four outcome groups over a division into "successful" /
      "not successful".

PMID- 11568864
TI  - [Variability of coping strategies in coronary artery bypass surgery patients].
AB  - The state-versus-trait discussion in coping research would become more meaningful
      if attention is paid to the variability both of coping patterns in individual
      patients as well as stability of single coping strategies over time. 35 patients
      undergoing coronary artery bypass surgery were interviewed three times about
      their coping and stress experience: after cardiac catheterization, on the day
      before surgery, and six days after surgery. Anxiety and depression were measured.
      A coping attitude of "positive passivity" was present at all three points of
      time. While the group means were stable, vast interindividual differences
      occurred. Also, there was a high degree of scatter in the stability of single
      coping items; emotion related coping modes were more stable than cognition and
      action related ones. The variability of the patients' coping patterns correlated
      positively with the amount of stress experienced and with preoperative
      depression. Different coping strategies are linked to a different degree with
      personality traits, emotional coping modes revealing the closest connection. The
      variability of individual coping efforts might be linked to a personality
      disposition characterized by a vulnerability for stress and depressive reactions.

PMID- 11568866
TI  - Esophageal function tests and successful esophageal surgery: Introduction.

PMID- 11568865
TI  - [Hypno-analysis: On the integration of hypnotic elements in individual uncovering
      psychotherapy in patients with anxiety disorder].
AB  - Following a short history of the development of the therapeutic techniques of
      psychoanalysis as derived from the basic rules of hypnosis, the apparent
      contradictions between the two approaches are called into question, with
      particular reference to the importance and efficacy of suggestion and
      suggestibility in both methods. How the integration of hypnotic interventions can
      both intensify and at the same time shorten the process of analytic therapy is
      demonstrated by two vignettes. The range of indications for the use of hypnosis
      as a complementary measure is currently restricted to the analysis of resistance
      and of the making conscious of past traumatic experiences that are involved in
      the psychogenesis of anxiety disorders. Particular importance is attached to the
      careful establishment of the indication and then psychoanalytic working-through
      of the accompanying transference-countertransference-dynamics following the
      completion of the hypno-analytic phase and in the course of the ongoing
      uncovering therapeutic process.

PMID- 11568867
TI  - Radiologic evaluation of the esophagus: methods and value in motility disorders
      and GERD.
AB  - The barium esophagram is an essential component in the workup of a patient with
      dysphagia and gastroesophageal reflux disease, especially when considering
      antireflux surgery or after such surgery. The examination requires a flexible
      approach with an emphasis on the motility portion of the examination. When
      properly performed, the examination should identify the following: normal or
      impaired esophageal emptying; normal or abnormal motility; the presence and type
      of hiatal hernia; the presence of a distal stricture or mucosal ring; and in many
      instances, the presence of gastroesophageal reflux. In patients after antireflux
      surgery, the examination should identify the following: normal of impaired
      esophageal emptying; normal or abnormal motility; the location, tightness, and
      length of the fundoplication; the presence of a recurrent hernia; and the
      presence of gastroesophageal reflux.

PMID- 11568868
TI  - Esophagoscopy and endoscopic esophageal ultrasound in the assessment of
      esophageal function.
AB  - Esophagoscopy is an ideal method to detect mucosal or structural abnormalities of
      the esophagus and proximal stomach. The exclusion of malignant dysphagia is the
      prime role of esophagoscopy in assessment of esophageal function. Esophagoscopy
      and biopsy are mandatory for mucosal assessment of patients with gastroesophageal
      reflux disease (GERD). Indirect and sometimes subtle evidence of abnormal
      esophageal motility is a valuable and underused aspect of esophagoscopy in the
      evaluation of swallowing disorders. Esophagoscopy has multiple roles in the
      appraisal and treatment of esophageal motility disorders, including the detection
      of secondary or pseudoachalasia, placement of manometry catheters, and dilation
      of peptic strictures caused by GERD associated with disorders such as
      scleroderma.

PMID- 11568869
TI  - Esophageal motility in the assessment of esophageal function.
AB  - Esophageal manometry assesses lower esophageal sphincter (LES) pressure and its
      relaxation. In addition, it detects the ability of the esophageal body to
      initiate a peristaltic contraction and the contraction's amplitude in response to
      a water bolus. The study is indicated in patients with symptoms suggestive of an
      esophageal motor disorder and to assist in the diagnosis of some miscellaneous
      disorders. The most common disorders diagnosed by esophageal manometry are the
      primary motility disorders, such as achalasia. Manometry is indicated in the
      subset of patients with gastroesophageal reflux disease (GERD) who are being
      considered for antireflux surgery or have symptoms after antireflux surgery.

PMID- 11568870
TI  - Twenty-four hour pH monitoring in the assessment of esophageal function.
AB  - Ambulatory 24-hour esophageal pH monitoring is an important test in the
      management of patients with gastroesophageal reflux disease. It quantifies
      esophageal acid exposure while patients pursue their everyday activities without
      restrictions. The test is performed with a compact portable data logger,
      miniature pH electrode, and computerized data analysis. The pH electrode should
      be positioned 5 cm above the manometrically defined lower esophageal sphincter.
      The patient is asked to press a button on the data logger indicating the onset of
      the symptom in question, which allows symptoms and acid reflux correlation.
      Twenty-four hour pH monitoring is generally performed after a therapeutic trial
      of antireflux medications, preferably proton pump inhibitors.

PMID- 11568871
TI  - New techniques in measuring nonacidic esophageal reflux.
AB  - New techniques in esophageal monitoring are allowing for better differentiation
      in the role of different gastric refluxates in esophageal mucosal damage and
      patient symptoms. The Bilitec 2001 (Synectics, Stockholm, Sweden) is a portable
      spectrophotometer that measures bilirubin as a surrogate marker for bile reflux
      and multichannel intraluminal impedance (MII) (Sandhill Scientific Inc, Highlands
      Ranch, CO) is a new technique allowing measurement of esophageal volume
      refluxate. Both techniques assess the role of nonacidic esophageal reflux.
      Despite their novel approach in assessing nonacid reflux, both methods have
      limitations. Future studies in this area, however, will prove beneficial in
      identifying their role in diagnosis and management of patients with suspected
      nonacid reflux disease.

PMID- 11568872
TI  - Autologous tissue in complex aortic valve disease.
AB  - Young patients with complex aortic valve disease involving the aortic root or
      ascending aorta are a challenge to manage. To use the Ross operation and realize
      its benefits, the operative technique must include aortic annulus reduction and
      fixation and replacement of ascending aortic pathology. Special techniques must
      be used when the cause of the complex disease is active endocarditis of the valve
      and aortic root. Surgical techniques that allow the use of the Ross operation in
      these settings and the midterm results in 84 patients are reviewed.

PMID- 11568873
TI  - Stentless bioprostheses in aortic root disease.
AB  - INTRODUCTION: The availability of aortic homografts is steadily decreasing. In
      the meantime, stentless xenografts convey similar flow characteristics, and
      tissue preservation methods are improving durability. Initially, these valves
      were contraindicated in aortic roots with discrepancy between annulus and
      sinotubular junction or with extensive calcification or sepsis. With increasing
      experience stentless xenografts are now applied in a wide spectrum of aortic root
      disease. METHODS: I reviewed our own experience with stentless aortic
      bioprosthesis for aortic valve replacement (AVR) and more taxing root problems. I
      used these valves in aortic aneurysm repair, acute Type A dissection, and for
      endocarditis with abcess formation. I studied valve hemodynamics, regression of
      left ventricular hypertrophy, and comparative survival with stented
      bioprostheses. RESULTS: Stentless bioprostheses convey hemodynamic and possibly
      survival benefit through a low incidence of valve-related complications. They
      provide a useful alternative to aortic homografts in endocarditis, Type A
      dissection, and aortic aneurysm surgery. CONCLUSIONS: Stentless bioprostheses are
      no longer confined to AVR alone. Experience supports the use of stentless
      bioprostheses where aortic homografts were previously applied. With availability
      in a wide range of sizes.

PMID- 11568874
TI  - Clinical use of stentless aortic valves with standard and minimally invasive
      surgical techniques.
AB  - The stentless porcine aortic valve prostheses have the potential to provide
      superior hemodynamic function and durability. Our institution was a trial site
      for the investigational device exemption (IDE) for 2 of the 3 stentless valve
      bioprostheses and has clinical experience in all 3 valves that are soon to be
      available. From July 1996 to January 2001, we have implanted 213 porcine
      stentless valves: the Toronto SPV (159), the Freestyle (20), and the Prima Plus
      (34) (current IDE). Fifty-five percent of these patients had concomitant coronary
      artery bypass graft procedures, 44% had isolated aortic valve replacements, and 3
      patients required aortic valve and mitral valve procedures. Fifty-nine percent of
      the patients were men, 9% of procedures were reoperations, and 22% of patients
      were in New York Heart Association classification III or IV preoperatively.
      Extubation occurred within 5 hours for 52% of patients, median cardiothoracic
      intensive care unit length of stay was 1 day, and postoperative length of stay
      was 6 days. Reoperations for bleeding occurred in 5.3% of patients (0 in the past
      12 months), atrial fibrillation in 28.2%, and permanent neurologic deficit in
      1.9%. No patients required valve-related reoperations or had either sepsis or
      sternal infections. Operative mortality was 1.4%. We have also analyzed a subset
      of patients who had minimally invasive aortic valve replacement versus the
      standard approach and found no important differences in mortality (none),
      postoperative complications, cardiopulmonary bypass, or cross-clamp times. There
      was a trend towards earlier ambulation, less atrial fibrillation (15.8% v 24.1%),
      and earlier hospital discharge (5.6 days v 7.2 days). We conclude that excellent
      results were obtained with all 3 stentless aortic valve bioprostheses. Hospital
      events should be predictably low in elderly patients and those requiring
      concomitant procedures. Stentless aortic valve bioprostheses can be incorporated
      into regular cardiac surgical practice with the techniques described.

PMID- 11568875
TI  - Aortic valve-sparing operations for aortic root aneurysm.
AB  - The object of this report is to review the clinical outcomes of aortic valve
      sparing operations in patients with aortic root aneurysm. From May 1988 to June
      2000, 120 patients with aortic root aneurysm with or without aortic insufficiency
      underwent aortic valve-sparing operations. There were 83 men and 37 women whose
      mean age was 46 years (range 16 to 72 years). Forty-eight patients had the Marfan
      syndrome, and 22 had either acute or chronic type A aortic dissections.
      Reconstruction of the aortic root was performed using the technique of
      reimplanation of the aortic valve in 64 patients and the remodeling of the aortic
      root in 56. The mean follow-up was 35 months (range 2 to 145 months), and it was
      complete. Aortic valve function was assessed by echocardiography. There were 2
      operative and 5 late deaths. The 10-year survival for patients with aortic root
      aneurysm was 88% +/- 4%. Two patients have required aortic root replacement: one
      on the first postoperative day because of severe aortic insufficiency and one
      paraplegic patient 12 years after surgery because of infective endocarditis with
      aortic root abscess. Both patients survived reoperation. The 10-year freedom from
      aortic root reoperation was 99% +/- 1%. Three patients suffered transient
      ischemic attacks. The 10-year freedom from thromboembolic events was 89% +/- 5%.
      Seven patients had moderate aortic insufficiency at the latest echocardiographic
      study. The 10-year freedom from severe or moderate aortic insufficiency was 83%
      +/- 8%. Aortic valve-sparing operations have provided excellent clinical outcomes
      and few valve-related complications. The function of the reconstructed aortic
      root remains unchanged in most patients during the first decade of follow-up.

PMID- 11568876
TI  - Competition and cooperation among huddling infant rats.
AB  - Huddling is expressed by infant rats and continues to be an important behavior
      throughout adulthood. As a form of behavioral thermoregulation, huddling is
      thought to play an essential role in compensating for inadequate physiological
      thermoregulation early in development. Infant rats, however, are capable of heat
      production shortly after birth using brown adipose tissue (BAT) and exhibit
      thermogenesis in the huddle, suggesting that huddling does not obviate the need
      for endothermy during cold exposure. In the present experiment, 4-pup huddles of
      infant rats (2- or 8-day-olds) were exposed to two subthermoneutral temperatures,
      and BAT thermogenesis was inhibited in 0, 2, or 4 of the rats in each huddle.
      Inhibition of BAT thermogenesis compromised the pups' ability to maintain huddle
      temperature, but surprisingly did not result in enhanced huddling at either age.
      These results suggest that effective huddling during cold exposure requires the
      thermal resources provided by endothermy. Furthermore, the heat provided by BAT
      appears to shape behavioral interactions in the huddle during development.

PMID- 11568877
TI  - Stress-induced sickness behaviors: an alternative hypothesis for responses during
      maternal separation.
AB  - During maternal separation, some primate and nonprimate species show a biphasic
      (active/passive) response. The second stage is characterized by reduced activity,
      a hunched body posture, and other behaviors. Traditionally, the second stage has
      been referred to as "despair" and is considered an animal model for human
      depression. Recent research in psychoneuroimmunology suggests an alternative
      hypothesis--that behaviors occurring during the second passive phase represent
      stress-induced "sickness behaviors." This perspective more readily accounts for
      findings in widely divergent species, does not require assumptions regarding the
      ability to express complex emotional states, is empirically testable, and aligns
      the separation model with recent hypotheses regarding the nature and ontogeny of
      depressive illness.

PMID- 11568878
TI  - Cross-species investigations of prenatal experience, hatching behavior, and
      postnatal behavioral laterality.
AB  - Turning biases have been reported in some mammalian species, but less is known
      about such biases in nonmammalians. This study investigated turning biases in
      domestic chicks, bobwhite and Japanese quail, leopard geckos, and snapping
      turtles. Domestic chicks (white leghorn and bantam) and bobwhite quail
      demonstrate strong group laterality. Japanese quail chicks, snapping turtles, and
      leopard geckos demonstrate no significant group bias. Results are discussed with
      regard to differences in embryonic experience, hatching behavior, and postnatal
      environment.

PMID- 11568879
TI  - Increase of learning abilities and maturation of the vertical lobe complex during
      postembryonic development in the cuttlefish, Sepia.
AB  - When shown prawns in a glass tube, cuttlefish quickly learn to inhibit their
      predatory behavior. By using a visual learning paradigm, we studied training and
      retention performances of cuttlefish aged from 8 to 90 days. We found an
      improvement in the acquisition of learning abilities during the first 2 months of
      life as well as an increase of 24-hr retention performance between 30 and 90 days
      of age. Using morphometric measurements of different lobes of the central nervous
      system, we correlated the emergence of these learning abilities with the
      postembryonic development of related nervous structures. Our results show that
      only the growth of the superior frontal and vertical lobes appears to be
      significantly correlated with the improvement of learning and long-term retention
      performances. Thus, as found in earlier data collected in Octopus, the vertical
      lobe complex of the cuttlefish seems to be involved in these learning processes.

PMID- 11568880
TI  - Stability of coupled fluctuations in movement and visual attention in infants.
AB  - Fluctuations in body movement and visual inspection were measured over minutes in
      3-month-old infants to look for evidence of coupling. In Experiment 1, infants (n
      = 12) looked ad libitum at two identical pictures for an average of 7.3 min.
      Analysis of the spontaneous fluctuations in movement and inspection revealed that
      they were inversely coupled: Moment-to-moment changes in movement and inspection
      occurred in opposite directions. In Experiment 2, after 4 min of free looking,
      infants (n = 33) were presented with a new pair of stimuli, a temporary change in
      the stimuli, or no change in stimuli. The inverse coupling between the
      fluctuations in body movement and visual inspection found in Experiment 1 was
      present before and after the stimulus changes, even in infants whose body
      movement decreased transiently in response to the stimulus changes. The
      reappearance of inversely coupled fluctuations in body movement and visual
      inspection following the stimulus changes was led by increases in movement. The
      results demonstrate the stability of the inverse coupling between spontaneous
      fluctuations in body movement and visual inspection, and suggest that changes in
      movement may lead changes in inspection.

PMID- 11568881
TI  - Cardiovascular indices of physiological arousal in boys with fragile X syndrome.
AB  - In this study, the relationship between physiological arousal, as indexed by
      heart rate variability, was examined in boys with fragile X syndrome (FXS) and
      typically developing boys matched on chronological age. In addition, the
      relationship of heart activity to clinical and molecular factors in the group of
      boys with FXS was examined. Results suggest that boys with FXS have higher levels
      of heart activity during the passive phases, as reflected in shorter heart
      periods. This high level of heart activity appears to be due to increased
      sympathetic activity and reduced parasympathetic activity. Boys with FXS did not
      display the expected patterns of heart activity in response to phases of
      increasing challenge, and sympathetic and parasympathetic systems did not appear
      coordinated in these boys with FXS. Clinical factors may be related to neural
      regulation of heart activity while molecular factors do not appear to be.

PMID- 11568882
TI  - Regulation of cognitive activity and early communication development in young
      autistic, mentally retarded, and young normal children.
AB  - Based on the Piagetian framework, this study examined regulation of cognitive
      activity and developmental communication profiles and their interrelationship in
      groups of autistic, mentally retarded, and normal children of comparable overall,
      verbal, and oculo-manual developmental ages (from 6 to 24 months). Regulation of
      activity was assessed with both an object permanence test and an original
      behavior grid, and development of communication skills with the Guidetti
      Tourrette scales (French adaptation of the Seibert-Hogan scales). The results
      showed evidence of certain types of dysregulation of cognitive activity and a
      general delay in communication ability in autistic children compared to the other
      two groups. Moreover, although the intensity of some of these disorders decreased
      in relation to the developmental levels of social interaction and joint attention
      in normal children, they were related to both high and low levels of development
      of social interaction only in autistic children. These findings raise the
      hypothesis of a relationship between a disorder of disengaging from an activity
      and developmental levels of social interaction noted at two transitory periods of
      early development (12 and 24 months) only in children with autism. Developmental
      and neuropsychological interpretations of this particular pattern are proposed.

PMID- 11568883
TI  - Identification of the components of taste mixtures by adults and children.
AB  - Recently, it was reported that cognitive factors may have impeded the analysis of
      binary taste mixtures by 8- to 9-year-old children, resulting in them identifying
      only the strongest component in each mixture compared to adults who identified
      both components (Oram, Laing, Freeman, & Hutchinson, 2001). The current study
      aimed to overcome this limitation by employing different training procedures and
      different instructions when conducting the task. In particular, the training
      involved familiarization with the two stimuli at several levels of perceived
      intensity to facilitate identification of the varying levels of each stimulus in
      mixtures. Using a selective attention procedure, adults and children were
      required to identify the components of stimuli that contained water, sucrose
      (sweet), sodium chloride (salty), or were binary mixtures of these two tastants.
      Both groups were successful in identifying the component(s) in each stimulus,
      demonstrating the importance of appropriate training and test procedures when
      studying the sensory responses of children. Together with data from the earlier
      study by Oram et al. (2001) it is concluded that 8- to 9-year-olds have the
      cognitive skills to analyze taste mixtures in terms of the identity of the
      components and their perceived strengths.

PMID- 11568885
TI  - Preface to genomic pathology--a new frontier.

PMID- 11568886
TI  - An introduction to arrays.
AB  - DNA microarrays are a new technology that allows the analysis of large numbers of
      genes at a high resolution by the hybridization of labelled DNA, which may be
      reverse-transcribed from mRNA, to a substrate containing thousands of spotted
      cDNAs or oligonucleotides. The amount of hybridized target is analysed, giving
      information on gene expression, polymorphisms or mutations present and allowing
      the gene profiling of different subtypes of disease. This technique has massive
      implications for the further understanding of the complicated genetic alterations
      involved in tumourigenesis and other disease processes and also for the
      generation of accurate prognostic information and optimization of treatment in
      these situations.

PMID- 11568887
TI  - Gene profiling techniques and their application in angiogenesis and vascular
      development.
AB  - The analysis of gene expression in specific tissues and physiological processes
      has evolved over the last 20 years from the painstaking identification of
      selected genes to the relatively efficient and open-ended surveying of
      potentially all genes expressed in a tissue. Current art for gene discovery
      includes the use of large-scale arrays of cDNA sequences or oligonucleotides, and
      molecular 'tagging' techniques such as GeneCalling and SAGE. Common to each of
      these techniques is a reliance on the increasingly comprehensive databases of
      human and mouse EST and full-length gene sequences. Early efforts to characterize
      candidate genes were limited by their narrow scope, while current efforts are
      confounded by the enormous volume of data returned. Sophisticated software tools
      are an integral part of the analysis, helping to organize information into
      coherent groups with temporal or functional similarity. These techniques, in
      conjunction with the continued analysis of human genetic syndromes, transgenic,
      and knockout mice, have driven genetic analysis of angiogenesis and vascular
      development from describing which individual genes are involved to defining the
      outlines of regulatory networks.

PMID- 11568888
TI  - The immune system and gene expression microarrays--new answers to old questions.
AB  - The recent increase in availability of gene expression technologies has the
      potential to dramatically expand our understanding of cellular immunology in
      molecular detail. Expression levels of tens of thousands of genes can be measured
      in dozens of samples in only a few days, and this data can be integrated with
      sequence informatics to tentatively assign some (limited) functional information
      to a majority of these genes. In this review we discuss some initial applications
      of these new tools to the fields of lymphocyte and monocyte differentiation
      pathways, the tolerance or immunity decision process, and B cell transformation.
      These examples illustrate the power of unbiased, 'wide-net', approaches both to
      drive immunological research in previously unexpected directions and to confirm
      classic tenets of immunology.

PMID- 11568889
TI  - The Cancer Genome Anatomy Project: new resources for reading the molecular
      signatures of cancer.
AB  - The Cancer Genome Anatomy Project (CGAP) has built informational, technological,
      and physical resources to interface genomics with basic and clinical cancer
      research. The CGAP web site (http://cgap.nci.nih.gov) provides informatics tools
      for in silico analysis of the CGAP datasets as well as information for accessing
      each of the CGAP resources. Published in 2001 by John Wiley & Sons, Ltd.

PMID- 11568890
TI  - Towards a novel classification of human malignancies based on gene expression
      patterns.
AB  - As a result of progress on the human genome project, approximately 19 000 genes
      have been identified and tens of thousands more tentatively identified as partial
      fragments of genes termed expressed sequence tags (ESTs). Most of these genes are
      only partially characterized and the functions of the vast majority are as yet
      unknown. It is likely that many genes that might be useful for diagnosis and/or
      prognostication of human malignancies have yet to be recognized. The advent of
      cDNA microarray technology now allows the efficient measurement of expression for
      almost every gene in the human genome in a single overnight hybridization
      experiment. This genomic scale approach has begun to reveal novel molecular-based
      sub-classes of tumours in breast carcinoma, colon carcinoma, lymphoma, leukaemia,
      and melanoma. In several instances, gene microarray analysis has already
      identified genes that appear to be useful for predicting clinical behaviour. This
      review discusses some recent findings using gene microarray technology and
      describes how this and related technologies are likely to contribute to the
      emergence of novel molecular classifications of human malignancies.

PMID- 11568891
TI  - Analysing gene expression data from DNA microarrays to identify candidate genes.
AB  - Microarray data analysis can be divided into two tasks: grouping of genes to
      discover broad patterns of biological behaviour, and filtering of genes to
      identify specific genes of interest. Whereas the gene-grouping task is largely
      addressed by cluster analysis, the gene-filtering task relies primarily on
      hypothesis testing. This review article surveys analytical methods for the gene
      filtering task. Various types of data analysis are discussed for four basic types
      of experimental protocols: a comparison of two biological samples; a comparison
      of two biological conditions; each represented by a set of replicate samples; a
      comparison of multiple biological conditions; and analysis of covariate
      information.

PMID- 11568892
TI  - Unlocking the archive--gene expression in paraffin-embedded tissue.
AB  - The histopathology archive represents a vast, well-characterized source of
      specimens covering virtually every disease and is available for molecular
      biological investigation. The archive has in recent years become widely used for
      molecular genetic analysis and DNA can be routinely extracted from formalin
      fixed, paraffin-embedded tissue. More recently, archival specimens have become a
      source of material for extensive analysis of mRNA expression utilizing DNA
      microarrays, real-time quantitative reverse transcriptase polymerase chain
      reaction (PCR), and in situ hybridization and amplification techniques. These
      techniques will enable a greater understanding of the changes that occur in gene
      function during every stage of the development of disease and will lead to better
      diagnosis, better evaluation of prognosis, and better treatment through targeted
      therapeutic regimes.

PMID- 11568893
TI  - Tissue microarray (TMA) technology: miniaturized pathology archives for high
      throughput in situ studies.
AB  - Tissue microarray (TMA) technology allows a massive acceleration of studies
      correlating molecular in situ findings with clinico-pathological information. In
      this technique, cylindrical tissue samples are taken from up to 1000 different
      archival tissue blocks and subsequently placed into one empty 'recipient'
      paraffin block. Sections from TMA blocks can be used for all different types of
      in situ tissue analyses including immunohistochemistry and in situ hybridization.
      Multiple studies have demonstrated that findings obtained on TMAs are highly
      representative of their donor tissues, despite the small size of the individual
      specimens (diameter 0.6 mm). It is anticipated that TMAs will soon become a
      widely used tool for all types of tissue-based research. The availability of TMAs
      containing highly characterized tissues will enable every researcher to perform
      studies involving thousands of tumours rapidly. Therefore, TMAs will lead to a
      significant acceleration of the transition of basic research findings into
      clinical applications.

PMID- 11568894
TI  - Use of laser capture microdissection, cDNA microarrays, and tissue microarrays in
      advancing our understanding of prostate cancer.
AB  - One difficulty in studying epithelial tumors has been the inability to isolate
      pure samples for DNA and RNA analysis. Prostate cancer, with its infiltrative
      nature, is particularly challenging. The Combination of several new technologies
      should help overcome these hurdles. Laser capture microdissection uses a laser
      beam to achieve transfer of pure cell populations for isolation of DNA, RNA, and
      protein. High-throughput analysis of these samples can be achieved by using cDNA
      expression microarrays. High-density tissue microarrays should allow for
      validation of differentially expressed genes. This review will concentrate on the
      application of laser capture microdissection, cDNA microarrays, and tissue
      microarrays in the area of prostate cancer research.

PMID- 11568895
TI  - Detection of novel gene expression in paraffin-embedded tissues by isotopic in
      situ hybridization in tissue microarrays.
AB  - Correlating altered gene expression patterns with particular disease states is a
      critical step in understanding disease processes and developing treatment
      strategies. Many thousands of novel gene sequences have recently been annotated
      in public and private databases and are now available for analysis. Tissue
      specific expression patterns of these sequences can be evaluated physically on
      DNA arrays and other high throughput assays, or virtually by bioinformatics
      mining of expressed sequence tag (EST) databases. As a secondary screening tool,
      in situ hybridisation (ISH) not only confirms tissue specificity, but also
      reveals what is often valuable information about cell-type expression patterns of
      nov16l sequences. Due to their availability and long-term stability at room
      temperature, formalin-fixed paraffin-embedded clinical specimens provide an
      invaluable resource for evaluating expression patterns of novel human genes. We
      describe a high-throughput approach for identifying and quantifying the
      expression of novel genes in paraffin-embedded human tissues using isotopic in
      situ hybridisation and tissue microarrays (TMA).

PMID- 11568896
TI  - DNA methylation in genomic imprinting, development, and disease.
AB  - Changes in DNA methylation profiles are common features of development and in a
      number of human diseases, such as cancer and imprinting disorders like Beckwith
      Wiedemann and Prader-Willi/Angelman syndromes. This suggests that DNA methylation
      is required for proper gene regulation during development and in differentiated
      tissues and has clinical relevance. DNA methylation is also involved in X
      chromosome inactivation and the allele-specific silencing of imprinted genes.
      This review describes possible mechanisms by which DNA methylation can regulate
      gene expression, using imprinted genes as examples. The molecular basis of
      methylation-mediated gene regulation is related to changes in chromatin structure
      and appears to be similar for both imprinted and biallelically expressed genes.

PMID- 11568897
TI  - Methylation and colorectal cancer.
AB  - Statistics rate colorectal adenocarcinoma as the most common cause of cancer
      death on exclusion of smoking-related neoplasia. However, the reported
      accumulation of genetic lesions over the adenoma to adenocarcinoma sequence
      cannot wholly account for the neoplastic phenotype. Recently, heritable,
      epigenetic changes in DNA methylation, in association with a repressive chromatin
      structure, have been identified as critical determinants of tumour progression.
      Indeed, the transcriptional silencing of both established and novel tumour
      suppressor genes has been attributed to the aberrant cytosine methylation of
      promoter-region CpG islands. This review aims to set these epigenetic changes
      within the context of the colorectal adenoma to adenocarcinoma sequence. The role
      of cytosine methylation in physiological and pathological gene silencing is
      discussed and the events behind aberrant cytosine methylation in ageing and
      cancer are appraised. Emphasis is placed on the interrelationships between
      epigenetic and genetic lesions and the manner in which they cooperate to define a
      CpG island methylator phenotype at an early stage in tumourigenesis. Finally, the
      applications of epigenetics to molecular pathology and patient diagnosis and
      treatment are reviewed.

PMID- 11568898
TI  - Screening for Wilms tumor and hepatoblastoma in children with Beckwith-Wiedemann
      syndromes: a cost-effective model.
AB  - BACKGROUND: We undertook a cost-benefit analysis of screening for Wilms tumor and
      hepatoblastoma in children with Beckwith-Wiedemann syndrome (BWS), a known cancer
      predisposition syndrome. The purpose of this analysis was twofold: first, to
      assess whether screening in children with BWS has the potential to be cost
      effective; second, if screening appears to be cost-effective, to determine which
      parameters would be most important to assess if a screening trial were initiated.
      PROCEDURES: We used data from the BWS registry at the National Cancer Institute,
      the National Wilms Tumor Study (NWTS), and large published series to model events
      for two hypothetical cohorts of 1,000 infants born with BWS. One hypothetical
      cohort was screened for cancer until a predetermined age, representing the base
      case. The other cohort was unscreened. For our base case, we assumed: (a)
      sonography examinations three times yearly (triannually) from birth until 7 years
      of age; (b) screening would result in one stage shift downward at diagnosis for
      Wilms tumor and hepatoblastoma; (c) 100% sensitivity and 95% specificity for
      detecting clinical stage I Wilms tumor and hepatoblastoma; (d) a 3% discount
      rate; (e) a false positive result cost of $402. We estimated mortality rates
      based on published Wilms tumor and hepatoblastoma stage specific survival.
      RESULTS: Using the base case, screening a child with BWS from birth until 4 years
      of age results in a cost per life year saved of $9,642 while continuing until 7
      years of age results in a cost per life-year saved of $14,740. When variables
      such as cost of screening examination, discount rate, and effectiveness of
      screening were varied based on high and low estimates, the incremental cost per
      life-year saved for screening up until age four remained comparable to acceptable
      population based cancer screening ranges (< $50,000 per life year saved).
      CONCLUSIONS: Under our model's assumptions, abdominal sonography examinations in
      children with BWS represent a reasonable strategy for a cancer screening program.
      A cancer screening trial is warranted to determine if, when, and how often
      children with BWS should be screened and to determine cost-effectiveness in
      clinical practice.

PMID- 11568899
TI  - Expression of cytokeratin-18-related tissue polypeptide-specific (TPS) antigen in
      Wilms tumor.
AB  - BACKGROUND: So far, there is no approved tumour marker for diagnosis or follow-up
      in Wilms tumour (WT). Tissue polypeptide-specific antigen (TPS), a cytokeratin 18
      proteolytic fragment, has been suggested to be of value in the clinical
      management of WT patients. Cytokeratin 18 fragments are an early indicator of
      apoptosis and cytokeratin 18 might influence tumour cell behaviour. We
      investigated TPS expression in specimens of WT and other paediatric renal
      malignancies PROCEDURE: Immunoreactivity of WT sections (n = 9), clear cell
      sarcomas (CCSK, n = 3), and a renal cell carcinoma (RCC), and two pediatric
      kidney tumour cell lines (WT: SK-NEP-1 and rhabdoid tumour of the kidney: G-401)
      were investigated using the monoclonal antibody M3. Additionally, immunoblotting
      and RT-PCR analysis were performed. Cell culture supernatants were evaluated for
      TPS release. Serum TPS was measured in five patients at diagnosis, during
      chemotherapy and after surgical resection. RESULTS: Moderate to strong
      immunoreactivity for TPS was found in tubular and blastemal components of nearly
      all (8/9) WT specimens. This was confirmed by Western-blotting. Cystic and
      epithelial-like portions of CCSKs and RCC showed distinct reactivity (3/3). The
      supernatant of G-401 but not of SK-NEP-1 showed a time- and cell number-dependent
      increase of TPS release. Interestingly, TPS synthesis was demonstrated in SK-NEP
      1 cells. Median preoperative serum TPS was elevated (293 U/l) compared to healthy
      children and lowest after surgical resection (49.5 U/l). CONCLUSIONS: This is the
      first study demonstrating the synthesis and release of TPS by WTs and other
      paediatric renal malignancies. Considering the elevated levels of TPS in serum of
      these patients, a further investigation of this marker by larger clinical trials
      seems to be justified.

PMID- 11568900
TI  - Intensive timed sequential remission induction chemotherapy with high-dose
      cytarabine for childhood acute myeloid leukemia.
AB  - BACKGROUND: Timed sequential chemotherapy and high-dose cytarabine (cytosine
      arabinoside, Ara-C; HDAC) are both effective treatments for acute myeloid
      leukemia (AML). We review our institutional experience with timed sequential
      induction chemotherapy consisting of daunorubicin/Ara-C/-thioguanine (DAT) or
      idarubicin/Ara-C/-thioguanine (IAT) followed on day 14 by HDAC regardless of the
      degree of marrow aplasia for children with newly diagnosed AML. PROCEDURE:
      Children presenting with newly diagnosed AML were treated with induction
      chemotherapy consisting of idarubicin (12 mg/m/day on days 1-3 or daunorubicin at
      45 mg/m(2)/day for the first five patients), Ara-C (100 mg/m(2)/day by continuous
      infusion on days 1-7), and thioguanine (100 mg/m(2)/day on days 1-7). HDAC (1
      g/m(2)/dose every 12 hr for 10 doses) was administered beginning on day 14,
      regardless of the results of bone marrow examination. RESULTS: Thirteen children
      received timed sequential HDAC. Only one child received HDAC later than Day 18.
      Eleven of the children achieved a complete remission. All patients experienced
      grade 4 hematologic toxicity, and all had fever as well. There were 11 children
      with documented infections. Ten had grade 3 or 4 GI toxicity. One patient died of
      sepsis. CONCLUSIONS: HDAC administered as a part of timed sequential therapy
      yields an excellent remission induction rate with manageable toxicity.

PMID- 11568902
TI  - Painful peripheral neuropathy after treatment with high-dose ifosfamide.
AB  - BACKGROUND: Ifosfamide is successfully employed in the treatment of bone and soft
      tissue sarcomas in children and young adults. Used at high doses (HDI) the drug
      may cause severe multiorgan toxicity. Peripheral neuropathy is a less well-known
      side effect that may limit its use. We describe a 16-year-old girl with a Ewing
      sarcoma who was given post-operative treatment with HDI (15 mg/m(2) infused over
      5 days). After the second course she experienced paresthesias in both feet. After
      the third course she developed signs of severe toxicity in the CNS, kidneys,
      heart, and severe pain in her feet. PROCEDURE: Neurologic and neurophysiologic
      investigations, including neurographic studies of motor and sensory nerves, EMG,
      and thermotest, were performed in the acute phase and after 6 and 21 months,
      respectively. Renal and cardiac function was also assessed. RESULTS: She
      developed generalized weakness of the arms and legs and an extremely painful
      hyperesthesia of the soles. The symptoms improved gradually during follow-up but
      remained to some extent even after more than 2 years. Serial neurophysiologic
      investigations indicated classical signs of axonal neuropathy, which tended to
      improve during follow-up. After 18 months the glomerular filtration rate and the
      effective renal plasma flow were 30 and 12% of normal, respectively, while other
      organ functions had returned to baseline. CONCLUSIONS: Symptoms of peripheral
      neuropathy after HDI may herald severe multiorgan toxicity, if continued. Early
      administration of anesthetics through the intrathecal route should be considered
      in case of ifosfamide-induced painful peripheral neuropathy.

PMID- 11568901
TI  - RB1 genetic testing as a clinical service: a follow-up study.
AB  - BACKGROUND: Genetic testing for inherited predisposition to diverse cancers has
      recently become available as a clinical service. We conducted a follow-up study
      of the initial series of US families who underwent RB1 genetic testing to
      evaluate long-term effects of the service. PROCEDURE: We enrolled 52 of 71
      eligible families who responded to a follow-up study questionnaire administered 3
      10 years after receipt of their RB1 results. Each family had one proband with
      unilateral, non-familial retinoblastoma, which is associated with a 12% pre-test
      probability of hereditary retinoblastoma. RB1 testing identified germline RB1
      mutations in five patients, lowered the carrier probability to 2% in 21 patients,
      and did not substantially modify the carrier probability in the remaining 26.
      RESULTS: Diverse medical specialists offered and arranged for RB1 testing, and
      their recommendation was the most influential factor in the decision to be
      tested. Pre-test counseling was provided by ophthalmologists (30), oncologists
      (11), and geneticists and genetic counselors (11). Most respondents, regardless
      of test result, were satisfied and perceived gains from their genetic testing.
      Based on small numbers, families with reduced likelihood of hereditary
      retinoblastoma reported more positive outcomes. Parents of RB1 carriers were more
      likely to seek medical services, worry, and decide against having more children.
      CONCLUSIONS: This study demonstrates the feasibility of follow-up studies of
      families who had genetic testing. Results from our small series suggest that
      genetic information and counseling are important components of RB1 clinical
      genetic testing, and long-term adverse effects of testing are uncommon.

PMID- 11568903
TI  - Metastatic Ewing sarcoma/PNET of bone at diagnosis: prognostic factors--a report
      from Saudi Arabia.
AB  - BACKGROUND: To evaluate outcome and prognostic factors in Saudi Arabian patients
      with metastatic Ewing sarcoma and PNET of bone (PMES) at diagnosis. PROCEDURE:
      Ninety-nine of 304 (33%) consecutive patients with Ewing sarcoma and PNET of bone
      registered at our centre from 1975 to 1998, had metastatic disease at
      registration and 93 were available for analysis. The maximum x-axis diameter of
      the primary tumor was used as the measure of primary tumor size. Usually a trial
      of systemic treatment was undertaken before a decision was made on local
      treatment. Standard chemotherapy regimens were used in all treated patients.
      Forty-one (44%) patients did not receive radical local treatment due to an
      inadequate response to chemotherapy, or a decision not to undertake more than
      palliative treatment. Radical treatment of the primary site was radiation alone
      41 (79%), resection alone 7 (13%), and resection and radiation 4 (8%). RESULTS:
      The 5-year survival rates were 9% for all 93 evaluable patients, 16% for 52
      patients who received chemotherapy and radical local treatment, 0% for 41
      patients who received lesser treatment, 19% for 43 patients with lung metastases
      alone, and 0% (P = 0.002) for 50 patients with other sites involved. For 60
      patients with imaging data, 5-year survivals were 34 and 0% when the maximum
      transverse diameter of the primary tumor was < 10 cm (N = 20) and > or = 10 cm (N
      = 40), respectively. CONCLUSIONS: Small primary tumor size and the presence of
      lung metastases alone were the only significant favorable prognostic factors.
      Earlier diagnosis will be the basis for better results.

PMID- 11568904
TI  - A phase I study of cranial radiation therapy with concomitant continuous infusion
      paclitaxel in children with brain tumors.
AB  - BACKGROUND: The prognosis of children with high-grade astrocytomas of the central
      nervous system is grim and has not been substantially improved by conventional
      chemoradiotherapy. We performed a multi-institutional phase I study to determine
      the toxicities and tolerance of concurrent external beam radiation of the brain
      and a unique dose-schedule of paclitaxel as a radiation sensitizer. PROCEDURE:
      Paclitaxel was delivered intravenously as a continuous 24 h/day, 7 days/week
      infusion during the entire 6-week course of fixed schedule standard radiation
      therapy. The dose of paclitaxel was escalated in patient cohorts in standard
      phase I design. RESULTS: Eleven patients (eight brain stem gliomas, one
      glioblastoma multiforme, and two gliomatosis cerebri) were treated. Dose-limiting
      toxicity was encountered in the two patients treated at 6 mg/(m(2)/24 h), both of
      whom developed severe obstipation requiring prolonged hospitalization.
      CONCLUSIONS: We have shown in this first study of its kind that paclitaxel can be
      administered safely to children as a 6-week continuous infusion concurrent with
      cranial irradiation. The maximally tolerated and recommended phase II dose is 4
      mg/(m(2)/day). The benefits of taxanes as clinical radiation sensitizers for
      children with high-grade gliomas, if any, remain to be determined.

PMID- 11568905
TI  - Analysis of handwriting of children during treatment for acute lymphoblastic
      leukemia.
AB  - BACKGROUND: Children treated for acute lymphoblastic leukemia (ALL) often
      complain about handwriting problems. PROCEDURE: Using a computerized writing
      task, we have prospectively studied the processes necessary for the production of
      handwriting movements in 11 children (5-12 years old) during treatment for ALL.
      Children were tested at time points closely related to the vincristine
      administration. RESULTS AND CONCLUSIONS: Children treated for ALL drew slower,
      with longer pause durations and increased drawing pressure. Children were able to
      overcome the problems, except for a consistently increased drawing pressure. This
      increased drawing pressure may be an attempt of the children to obtain sufficient
      kinesthetic information and thus can be seen as an adequate adaptation mechanism
      in case of peripheral neuropathy due to the neurotoxic effects of vincristine.
      However, neurotoxic effects of other cytostatic drugs cannot be excluded.

PMID- 11568907
TI  - Margarita Statement, Sociedad Latinoamericana de Oncologia Pediatrica (SLAOP):
      Latin American Society of Pediatric Oncology.

PMID- 11568906
TI  - Childhood cancer in Uruguay: 1992-1994. Incidence and mortality.
AB  - BACKGROUND: The referral of all children with cancer in Uruguay to a single
      center affords the opportunity to generate population-based incidence and
      mortality rates in this developing country in Latin America. PROCEDURE: All
      incident cases of cancer in children, 0-14 years of age, were ascertained from a
      combination of three sources for the period January 1992-December 1994. Diagnoses
      were grouped according to the International Classification of Childhood Cancer.
      Information on the size and age distribution of the total population was obtained
      from national census records. Follow-up was undertaken until December 1999 to
      afford a minimum interval of 5 years and the determination of mortality rates.
      RESULTS: The average annual incidence was 133.6 cases of cancer per million
      children per year and the disease distribution was similar to that in
      industrialized countries, with the exception of a higher rate and younger age
      distribution for the Hodgkin disease. The overall age-standardized mortality rate
      from cancer in childhood, at 6.5 per 100,000, was approximately twice that in the
      United States and Canada. CONCLUSIONS: Basic indicators of development suggest
      that Uruguay is more akin to the countries of North America and Western Europe
      than to those in the developing world. An opportunity has been identified to
      improve the outcome for children with cancer in this country.

PMID- 11568908
TI  - Pages from the logbook of a pediatrician: Ike and me.

PMID- 11568909
TI  - Characteristics of TEL/AML-1 positive acute lymphoblastic leukemia in Hungarian
      children.

PMID- 11568910
TI  - Eccrine porocarcinoma in a child that evolved rapidly from an eccrine poroma.

PMID- 11568911
TI  - Absence of t(12;15) associated ETV6-NTRK3 fusion transcripts in pediatric acute
      leukemias.

PMID- 11568912
TI  - Absence of t(12;15) associated ETV6-NTRK3 fusion transcripts in pediatric acute
      leukemias.

PMID- 11568913
TI  - Does a "false-negative" MIBG scan predict a better outcome in neuroblastoma
      patients?

PMID- 11568914
TI  - Partial urorectal septum malformation sequence: a report of 25 cases.
AB  - We have identified 25 cases with what we are calling the partial urorectal septum
      malformation (URSM) sequence, which were seen in our institution over the past 27
      years. The partial URSM sequence is defined as a single perineal/anal opening
      that drains a common cloaca in combination with an absent (imperforate) anus. In
      the 25 patients reported here, the partial URSM sequence was more common in
      females, with a female to male ratio of 18 to 7. Ambiguous genitalia were common
      in both sexes. Internal pelvic structures typically showed a cloaca with the
      bladder and rectum (and vagina in females) coalescing into a common canal that
      connected to the external surface in the perineal or anal area. Abnormalities of
      the internal genitalia were also common, with 12 females having a bifid or
      septate vagina and 11 having a bicornuate uterus. Renal anomalies were frequent
      in both sexes, with 10 of 25 patients having unilateral cystic renal dysplasia
      and 7 of 25 patients having unilateral renal agenesis. Twenty-one of 25 patients
      survived long term. By definition, the partial URSM sequence is a milder
      expression of the full URSM sequence, which is defined as having no perineal or
      anal openings and is typically associated with an internal cloaca. The URSM
      spectrum, which encompasses the partial and full URSM sequences, is believed to
      be caused by abnormalities of septation of the primitive cloaca. The URSM
      spectrum is distinct from the VATER association and conditions caused by sex
      hormone abnormalities, such as congenital adrenal hyperplasia.

PMID- 11568915
TI  - Parental attitudes toward a diagnosis in children with unidentified multiple
      congenital anomaly syndromes.
AB  - One of the most common and unsatisfying situations encountered in medical
      genetics clinics is the child with multiple congenital anomalies (MCAs)
      suggestive of an underlying syndrome for whom it is not possible to make a
      definitive diagnosis. We undertook a qualitative, descriptive study to learn more
      about the ways in which the lack of a diagnosis affects parental coping and
      adjustment to their child's special needs. Semistructured interviews were
      conducted with 29 parents of 16 children born with an unidentified MCA syndrome.
      Interviews were based on a small number of open-ended questions, with follow-up
      probing, asking about parents' experiences with seeking a diagnosis, obtaining
      treatment and special services, explaining their child's problems to others,
      reproductive decision making, and support group participation. Transcripts of
      interviews were analyzed to identify the principal themes surrounding parents'
      beliefs about the significance of diagnostic information. The parents in this
      study had been aware of their child's anomalies for 2-23 years, and all had
      sought multiple evaluations to find a diagnosis. A majority of parents were still
      interested in identifying their child's syndrome, but most felt that their
      interest in a diagnosis had diminished over time, and some felt that there were
      benefits in not having this information. We identified six areas where parents
      claimed a diagnosis would have impact: labels, causes, prognosis, treatment,
      acceptance, and social support. Significant issues included obtaining special
      education services, anticipating the child's future and potential medical
      complications, life expectancy, recurrence risks, finding sources of social
      support, and ensuring that the child was receiving appropriate treatment. We
      conclude that the significance of diagnostic information is complex and varies
      for different parents. Providers should explore the underlying issues associated
      with a parental quest for a diagnosis in order to identify and address specific
      concerns. Published 2001 Wiley-Liss, Inc.

PMID- 11568916
TI  - Comparative analysis of PCR-deletion detection and immunohistochemistry in
      Brazilian Duchenne and Becker muscular dystrophy patients.
AB  - We studied 48 patients with dystrophinopathies (29 Duchenne muscular dystrophy
      (DMD), 13 Becker muscular dystrophy (BMD), four possible carriers, one female
      with DMD, and one intermediate form, using polymerase chain reaction (PCR)
      analysis of muscle tissue for 20 exons and compared them with
      immunohistochemistry studies for dystrophin. Of these, 42 (87.5%) showed at least
      one intragenic deletion. Most of them (47.45%) involved exons 2 to 20. All BMD
      patients presented deletions on the dystrophin gene. The 29 patients with DMD
      showed abnormal dystrophin in immunohistochemistry studies, some with total
      absence (17/29), others with residual (3/29), and the remaining with scattered
      positive fiber (9/29). The majority of the 13 patients with BMD had abnormal
      immunohistochemistry studies with diffuse reduction in the majority of muscle
      fibers (10/13), a few with patch discontinuation in the sarcolemma (2/13), and
      one normal (1/13). The immunohistochemistry exam for dystrophin is still the gold
      standard method for DMD/BMD diagnosis. An ethnic difference, the analysis of
      several exons, the sample size, and the use of muscle tissue could explain this
      high frequency of deletions in the dystrophin gene found in our cases.

PMID- 11568917
TI  - Mortality and apolipoprotein E in Hispanic, African-American, and Caucasian
      elders.
AB  - To investigate whether mortality risk is influenced by apolipoprotein E (APOE)
      genotype and whether the risk differs by ethnicity, we compared the mortality
      risk in 2,112 individuals > or = 65 years of age residing in northern Manhattan
      in New York. Mortality risks associated with the APOE genotype, adjusted for sex,
      high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides,
      differed significantly by ethnic group. Among Caucasian and Hispanics, the E2/E3
      genotype was associated with the lowest mortality risk in the multivariate Cox
      proportional hazards modeling, adjusted for lipid levels, whereas mortality risk
      did not differ substantially between the E4/E3 and E3/E3 genotypes. Among African
      Americans, the E2/E3 genotype was not associated with the lowest mortality risk,
      but the E4/E3 genotype was. Adjustment for heart disease, diabetes, and stroke
      reduced mortality risk associated with each genotype by about 50% for all ethnic
      groups, but the patterns remained the same. Although we cannot rule out the
      possibility of a healthy survival bias, our analyses designed to examine healthy
      survival by comparing risk of mortality in groups who were younger or older at
      entry do not support this possibility. Our findings suggest that the APOE
      genotype is associated with mortality and that the genotypic risks differ by
      ethnic group. Nearly 50% of the mortality risk associated with the APOE genotype
      appears to act through major chronic diseases, but those diseases only partially
      explain the mechanism by which the genotypic risk acts. To better understand the
      observed ethnic differences in mortality risk by genotype, a detailed prospective
      study is needed to examine the relationships among APOE, other candidate genes,
      health conditions, and eventual death.

PMID- 11568918
TI  - Abnormal folate metabolism and genetic polymorphism of the folate pathway in a
      child with Down syndrome and neural tube defect.
AB  - The association of neural tube defects (NTDs) with Down syndrome (trisomy 21) and
      altered folate metabolism in both mother and affected offspring provide a unique
      opportunity for insight into the etiologic role of folate deficiency in these
      congenital anomalies. We describe here the case of a male child with trisomy 21,
      cervical meningomyelocele, agenesis of corpus callosum, hydrocephaly, cerebellar
      herniation into the foramen magnum, and shallow posterior cranial fossa.
      Molecular analysis of the methylenetetrahydrofolate (MTHFR) gene revealed
      homozygosity for the mutant 677C-->T polymorphism in both the mother and child.
      The plasma homocysteine of the mother was highly elevated at 25.0 micromol/L and
      was associated with a low methionine level of 22.1 micromol/L. Her S
      adenosylhomocysteine (SAH) level was three times that of reference normal women,
      resulting in a markedly reduced ratio of S-adenosylmethionine (SAM) to SAH and
      significant DNA hypomethylation in lymphocytes. The child had low plasma levels
      of both homocysteine and methionine and a reduced SAM/SAH ratio that was also
      associated with lymphocyte DNA hypomethylation. In addition, the child had a five
      fold increase in cystathionine level relative to normal children, consistent with
      over-expression of the cystathionine beta synthase gene present on chromosome 21.
      We suggest that altered folate status plus homozygous mutation in the MTHFR gene
      in the mother could promote chromosomal instability and meiotic non-disjunction
      resulting in trisomy 21. Altered folate status and homozygous TT mutation in the
      MTHFR gene in both mother and child would be expected to increase the risk of
      neural tube defects. The presence of both trisomy 21 and postclosure NTD in the
      same child supports the need for an extended periconceptional period of maternal
      folate supplementation to achieve greater preventive effects for both NTD and
      trisomy 21.

PMID- 11568919
TI  - Mutation of the PRNP gene at codon 211 in familial Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD) belongs to a group of chronic, progressive,
      neurodegenerative disorders that may be hereditary, infectious, or sporadic.
      Hereditary CJDs are associated with mutations in the PRNP gene on chromosome
      20p12-pter. We report a family in which four patients developed classical
      clinical signs of CJD, including severe cognitive decline, cerebellar signs,
      myoclonic jerks, and synchronic periodic discharges on electroencephalogram. The
      E211Q mutation has been identified in family members, but not in 97 sporadic CJD
      patients referred to the Italian registry of CJD nor in 205 healthy normal
      subjects, suggesting a pathogenic role for this mutation.

PMID- 11568921
TI  - Wiedemann-Rautenstrauch (neonatal progeroid) syndrome: new case with normal
      telomere length in skin fibroblasts.
AB  - Wiedemann-Rautenstrauch (neonatal progeroid) syndrome is an autosomal recessive
      condition with characteristic appearance of premature aging present at birth
      (aged face, natal teeth, and wrinkled skin). Other features of the syndrome are
      generalized lipoatrophy with specific fat accumulation in the lateral
      suprabuttock region, hypotrichosis, macrocephaly (pseudohydrocephalus), and
      mental retardation. We report on a new case that demonstrates all typical
      features of the syndrome. The girl is now 16 years and 10 months old and has had
      follow-up from birth. We measured terminal restriction fragment (TRF) length to
      evaluate whether the patient's premature aging process is accompanied by
      shortening of telomere length in her cultured fibroblasts. Mean TRF of 13.5 kb
      found in our patient's fibroblasts is not shortened as compared to that of normal
      fibroblasts. Our results differ from those observed in Hutchinson-Gilford
      progeria.

PMID- 11568920
TI  - Systematic genetic study of Alzheimer disease in Latin America: mutation
      frequencies of the amyloid beta precursor protein and presenilin genes in
      Colombia.
AB  - Nearly all mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), and
      amyloid beta precursor protein (APP) genes lead to early-onset Alzheimer disease
      (EOAD, onset age at or before 65 years). In order to assess the genetic
      contribution of these genes in a series of Colombian AD cases, we performed a
      systematic mutation analysis in 11 autosomal dominant, 23 familial, and 42
      sporadic AD patients (34% with age of onset < or = 65 years). No APP missense
      mutations were identified. In three autosomal dominant cases (27.2%), two
      different PSEN1 missense mutations were identified. Both PSEN1 mutations are
      missense mutations that occurred in early-onset autosomal AD cases: an I143T
      mutation in one case (onset age 30 years) and an E280A mutation in two other
      cases (onset ages 35 and 42 years). In addition, a novel PSEN1 V94M mutation was
      present in one early-onset AD case without known family history (onset age 53
      years) and absent in 53 controls. The E318G polymorphism was present in five AD
      cases and absent in controls. In PSEN2, two different silent mutations were
      detected, including one not reported elsewhere (P129). The majority of the
      Colombian AD cases, predominantly late-onset, were negative for PSEN and APP
      mutations.

PMID- 11568922
TI  - Search for ethnic, geographic, and other factors in the epidemiology of Down
      syndrome in South America: analysis of data from the ECLAMC project, 1967-1997.
AB  - We have analyzed data on 3,157 cases of Down syndrome (DS) from nine South
      American countries in consecutive series of hospital live births over a 30-year
      period, with particular emphasis on possible ethnic or geographic variations in
      maternal age-adjusted incidence. The data constitute the largest series of DS
      cases assembled to date from an area lacking advanced health care systems.
      Absolute incidence rates were estimated from total hospital live births; relative
      rates were estimated from matched case-control data using conditional logistic
      regression. Maternal age-adjusted rates were closely similar to those reported
      elsewhere, and showed little or no dependency on other factors investigated,
      including paternal age, birth order, ancestral origin, country of birth, maternal
      educational level, maternal ABO and Rhesus blood groups, interval to and outcome
      of mother's previous pregnancy, and parental consanguinity. The absence of an
      effect of high birth order was particularly notable because of the relatively
      large number of grand multipara resulting from high fertility in this population.
      The study adds to a body of evidence suggesting that maternal age-adjusted DS
      rates vary little across human populations, and are therefore unlikely to be
      greatly influenced by genetic or environmental factors that differ between them.
      An unusual finding was of a markedly lower sex ratio (98 males per 100 females)
      than has been reported in other DS samples.

PMID- 11568923
TI  - Possible case of Pitt-Hopkins syndrome in sibs.
AB  - In this article, we describe two sibs, a brother and sister, with severe mental
      retardation and multiple congenital anomalies including "coarse" facial features,
      short stature, seizures, hypertrichosis, short great toes, and overbreathing.
      Comparison of these patients with previous reports suggests that they could
      represent the first familial cases of the Pitt-Hopkins syndrome. The recurrence
      in sibs within the same family supports autosomal recessive inheritance for the
      condition. Variable expression of the respiratory symptoms, which has not been
      reported earlier, is underlined.

PMID- 11568924
TI  - Additional dark G-band in the p-arm of chromosome 19 due to a paracentric
      inversion with a breakpoint in the pericentromeric heterochromatin.
AB  - Paracentric inversions in chromosome 19 have rarely been described. Here we
      present an inv(19)(p11p13.1) with a breakpoint in the pericentromeric
      heterochromatin which leads to an additional dark G-band in the p-arm of
      chromosome 19. The rearranged chromosome segregated in two generations of a
      family without any phenotypic effects. A detailed characterization of the inv(19)
      by molecular cytogenetic techniques is presented.

PMID- 11568925
TI  - Case of Myhre syndrome with autism and peculiar skin histological findings.
AB  - Myhre syndrome (MS) (MIM 139210) is a rare disorder characterized by short
      stature, mental retardation, muscular build, blepharophimosis, and decreased
      joint mobility. We report on a 14-year-old boy with clinical findings consistent
      with a diagnosis of Myhre syndrome, associated with autism and peculiar skin
      histological findings.

PMID- 11568927
TI  - Benign idiopathic partial seizures in the velocardiofacial syndrome: report of
      two cases.
AB  - We describe two children with the velocardiofacial syndrome and benign partial
      onset seizures. Both presented with slight dysmorphic traits, mild to moderate
      mental delay, and high-arched palate. A cardiac defect was present in only one of
      them. In each patient, sporadic rolandic or occipital partial-onset seizures with
      the clinical and electroencephalographic features of benign idiopathic childhood
      epilepsy manifested at age 3 and 5 years, respectively. Treatment was started
      only in one patient, with complete seizure control. These two cases show that
      benign partial epilepsy can be a component manifestation of the central nervous
      system-related symptoms of the velocardiofacial syndrome.

PMID- 11568926
TI  - Alagille syndrome associated with a paracentric inversion 20p12.2p13 disrupting
      the JAG1 gene.
AB  - Mutations in the human gene Jagged1 (JAG1) localized in 20p12 have been recently
      identified as causal for the anomalies found in patients with Alagille syndrome
      (AGS). This gene encodes a ligand for the Notch1 transmembrane receptor, which
      plays a key role in cell-to-cell signaling during differentiation and is
      conserved from C. elegans to human. We report a paracentric inversion (PAI) of
      chromosome 20p12.2p13 in an individual with AGS who also had alpha-1-antitrypsin
      deficiency. To our knowledge, this is the first published case of PAI involving
      the short arm of chromosome 20. Using FISH, fiberFISH, and molecular studies with
      a approximately 40 kb cosmid clone encompassing the entire 36 kb JAG1 gene, we
      demonstrate that the gene was disrupted by the inversion breakpoint between exons
      5 and 6. An unusual association between two most common causes of chronic liver
      disease in childhood, AGS and alpha-1-antitrypsin deficiency, as well as their
      influence on the proband's abnormal phenotype are discussed.

PMID- 11568928
TI  - An 8-cM interstitial deletion on 4q21-q22 in DNA from an infant with
      hepatoblastoma overlaps with a commonly deleted region in adult liver cancers.
AB  - We performed molecular analysis of a germline interstitial deletion of chromosome
      4 [del(4)(q21.22q23)], which had been observed in a male infant manifesting early
      onset hepatoblastoma (HBL). The chromosomal anomaly in this child was associated
      with a unique congenital syndrome including HBL, atrial septal defect,
      ventricular septal defect, patent ductus arteriosus, mental retardation, and
      seizures. However, the patient did not exhibit a megalencephaly typical of 4q21
      22 deletions. His HBL was associated with an increasing serum alpha-fetoprotein
      level and rapid growth. To define the chromosomal deletion at the molecular level
      in this child, we analyzed his lymphoblasts with fluorescence in situ
      hybridization, using as probes a panel of BAC/PAC genomic clones containing STS
      markers covering the 4q12-27 region. The analysis revealed that the affected
      chromosome had an 8-cM deletion within 4q21-q22, flanked by markers D4S2964 and
      D4S2966. This microdeletion overlaps with the commonly deleted region at 4q21-q22
      that was recently defined in adult hepatocellular carcinomas.

PMID- 11568929
TI  - Reply to Shaffer regarding reply to "Burning down DEFECT11".

PMID- 11568930
TI  - Provocation study of persons with perceived electrical hypersensitivity and
      controls using magnetic field exposure and recording of electrophysiological
      characteristics.
AB  - The aim of the present study was to investigate possible neurophysiological
      effects of intermittent 15 sec on/off cycle, 60 Hz, 10 microT magnetic field
      exposure on patients with perceived "electromagnetic hypersensitivity" (EHS), and
      control subjects during rest and performance of a mental arithmetic task. Twenty
      participants (15 female, 5 male, 31-60 years old, mean 45.8 +/- 0.7 years) were
      invited from the group of EHS patients. Twenty volunteers (15 female, 5 male, 31
      59 years old, mean 45.0 +/- 0.7 years?) served as a control group. The test
      protocol consisted of a set of examinations: EEG, visual evoked potentials,
      electrodermal activity, ECG, and blood pressure. The total duration of the test
      was 40 min, divided into two 10 min rest periods and two 10 min periods of
      mathematical performance. Magnetic field and sham exposures were presented
      randomly during these periods, resulting in four different conditions: Field
      Rest, Sham-Rest, Field-Math, and Sham-Math. The data showed significant main
      effects of the Group factor (EHS vs. control subjects) on heart rate (F(1,80) =
      20.6; P < 0.01), heart rate spectrum ratio (F(1,80) = 9.5; P = 0.02), and
      electrodermal activity (F(1,76) = 4.2; P = 0.04), whereas EEG characteristics did
      not differ between groups. The Condition factor (mathematical task vs. relaxed)
      showed main effects for heart rate (F(1,80) = 14.8; P < 0.01), heart rate
      spectrum ratio (F(1,80) = 7.8; P = 0.06), electrodermal activity (F(1,76) = 56.8;
      P < 0.01), and alpha and theta spectral bands of EEG. Magnetic field exposure did
      not affect autonomous system or electroencephalographic variables of either
      group. These data do not indicate that EHS patients or control are affected by
      low-level 60 Hz magnetic field exposure. However, persons reporting EHS differed
      from the control subjects in baseline values of investigated physiological
      characteristics. Perhaps EHS patients have a rather distinctive physiological
      predisposition to sensitivity to physical and psychosocial environmental
      stressors.

PMID- 11568931
TI  - Numerical computation of distortions in magnetic fields and induced currents in
      physiological solutions produced by microscope objectives.
AB  - Identifying distortions produced by commonly employed microscope objectives and
      their components in uniform DC and 60 Hz AC magnetic fields is important in
      imaging studies involving exposure of cells to spatially uniform or nonuniform
      magnetic fields. In this study, DC and 60 Hz AC magnetic flux densities were
      numerically computed in the presence of finite element models of various
      components of commonly utilized microscope objectives, as well as a model of a
      complete objective. Also computed were the distortions in the current density
      induced by an applied time-varying magnetic field in a physiological buffer
      contained within a Petri dish. We show that the magnetic flux density could be
      increased up to 65% in the presence of the nickel-chrome plating of an objective
      housing and that the presence of ferromagnetic components like a screw or spring
      could produce peaks that are 7% higher than the undistorted value of magnetic
      flux density. In addition, a slight tilt of 1% in the objective with respect to
      the magnetic field could cause a 93% deviation in magnetic flux density from the
      unperturbed value. These results correlate well with previously published
      experimental measurements that showed the presence of significant and sometimes
      asymmetric distortions in both DC and 60 Hz magnetic fields. Moreover, this study
      further reports that induced current density changed up to 37% compared to values
      in the absence of the objective. The existence of distortions in applied magnetic
      fields and induced currents could affect the interpretation of results of cell
      function studies if it is assumed that the cells are exposed to uniform magnetic
      flux densities in the presence of a microscope objective. Such assumptions of
      uniform magnetic flux density could also account for the lack of reproducibility
      in several studies that examined changes in intracellular calcium by imaging
      techniques.

PMID- 11568932
TI  - Direct current decreases cell viability but not P-glycoprotein expression and
      function in human multidrug resistant leukemic cells.
AB  - Inhibition of tumor growth induced by treatment with direct current (DC) has been
      reported in several systems. In the current work, the cellular effects generated
      by the DC treatment of the human leukemic K562 cell line and its vincristine
      resistant derivative K562-Lucena 1 were analyzed by trypan blue staining and
      transmission electron microscopy. DC stimulation induced cell lysis, alterations
      in shape, membrane extraction or discontinuity, and intense vacuolization of some
      cells. In addition, treatment of K562 and K562-Lucena 1 cells caused a marked
      decrease in viability. Since multidrug resistance is a major factor contributing
      with failure of chemotherapy in many tumors, the expression and function of P
      glycoprotein (P-gp) in K562-Lucena 1 cells were also studied. The expression of
      mdr1, the gene encoding P-gp, was analyzed by reverse transcription polymerase
      chain reaction, which showed that this gene was equally expressed in either
      treated or untreated cells. These results were confirmed by flow cytometry with a
      monoclonal anti P-gp antibody and the Rhodamine 123 extrusion method, which
      revealed that P-gp surface expression and function were unaltered after DC
      treatment. Our results suggest that DC treatment does not affect P-gp in human
      leukemic cells, but affects their viability by mechanisms that would involve
      clear cellular effects, but also additional targets, whose relevance in dc
      treated tumoral cells is currently discussed.

PMID- 11568933
TI  - Influence of alternating low frequency magnetic fields on reactivity of central
      dopamine receptors in neonatal 6-hydroxydopamine treated rats.
AB  - The aim of this study was to evaluate the influence of extremely low frequency
      magnetic field (ELF MF) on the reactivity of the central dopamine D(1) receptor
      in rats with dopamine neurons chemically damaged by 6-hydroxydopamine (6-OHDA),
      an animal model of human's Parkinson's disease. The experiment was carried out on
      male Wistar rats. On day 3 of postnatal life, a lasting and selective chemical
      damage of the central dopamine system was induced in the rats by infusion of 6
      OHDA HBr (133.4 microg intracerebroventricular, base form) given bilaterally into
      lateral ventricles of the brain. Control animals received similar treatments
      injecting only vehicle. At 2 months of age, both 6-OHDA treated and control rats
      were randomly divided into two groups. Rats from the first group were exposed to
      10 Hz sinusoidal, 1.8-3.8 mT magnetic field one hour daily for 14 days. Rats of
      the second group were sham exposed, with the applicator solenoid turned off. On
      the day after the final exposure the evaluations were made of the rat's
      spontaneous irritability, oral activity, and catalepsy. The MF exposed rat with
      chemically induced dopamine neurons damage exhibited a reduction of irritability
      and oral activity when stimulated with SKF 38393 (the agonist of central dopamine
      D(1) receptor) and some increase of catalepsy after administration of SCH
      23390(the antagonist of central dopamine D(1) receptor). These results indicate
      that ELF MF reduce the reactivity of central dopamine D(1) receptors in rats.

PMID- 11568934
TI  - Frequency response of alternating currents through the Staphylococcus aureus
      alpha-hemolysin ion channel.
AB  - Alternating currents were measured through transmembrane ion channels formed by
      Staphylococcus aureus alpha-hemolysin proteins in planar bilayer membranes as
      part of an investigation to determine the channel's frequency response and the
      appropriateness of an equivalent circuit commonly used to model electrical
      interactions at the surface of cells. The experimental approach includes a novel
      method for separating the alternating current through one or more channels, which
      is conductive in nature, from the capacitively coupled current through the
      membrane. Separation of the conductive and capacitive alternating currents made
      it possible to measure the frequency response of the alpha-hemolysin channels.
      The results of the study are consistent with an equivalent circuit of a membrane
      capacitor in parallel with one or more channel resistors over the frequency range
      30-120 Hz. The possible usefulness of frequency response data for ion channels in
      cell membranes during investigations of biological effects of time-varying
      magnetic fields is briefly discussed.

PMID- 11568935
TI  - Effects of permanent magnets on resting skin blood perfusion in healthy persons
      assessed by laser Doppler flowmetry and imaging.
AB  - Effects on skin blood perfusion of permanent ceramic magnets [0.1 T (1000 G)
      surface field], individually (disk shaped, 4 cm diameter x 1 cm thick) or in the
      form of a 11 x 7 in pad ( approximately 28 x 17.8 cm) with an array of 16
      rectangular magnets (4.5 x 2.2 cm), were investigated in 16 female volunteers
      (27.4 +/- 1.7 years, range 21-48 years) using three separate protocols. In
      protocol A, a disk magnet was placed on the palmar surface of the hand in contact
      with the thenar eminence (n = 5). In protocol B, the magnet was placed on the
      hand dorsum overlying the thenar eminence (n = 5). In protocol C, the entire palm
      and fingers rested on the magnetic pad (n = 6). Magnets were in place for 36 min
      on one hand, and a sham was in place on the other hand. Blood perfusion was
      measured on the middle finger dorsum by laser Doppler flowmetry (LDF) and on the
      index finger by laser Doppler imaging (LDI). Perfusion measurements were
      simultaneously taken in sham and magnet exposed hands, before and during the
      entire magnet exposure interval. Magnetic field effects were tested by comparing
      skin blood perfusion sequences in magnet and sham exposed regions. Results showed
      no significant changes in either LDF or LDI perfusion at magnet or sham sites
      during exposure, nor were there any significant differences between sham and
      magnet sites for any protocol. Measurements of skin temperature at the LDF
      measurement sites also showed no significant change. It is concluded that in the
      healthy subjects studied with normal, unstressed circulation, magnets of the type
      and for the duration used, showed no detectible effect on skin blood perfusion in
      the anatomical area studied.

PMID- 11568936
TI  - Pulsed electromagnetic fields affect the intracellular calcium concentrations in
      human astrocytoma cells.
AB  - Experiments assessed whether long term exposure to 50 Hz pulsed electromagnetic
      fields with a peak magnetic field of 3 mT can alter the dynamics of intracellular
      calcium in human astrocytoma U-373 MG cells. Pretreatment of cells with 1.2
      microM substance P significantly increased the [Ca(2+)](i). The same effect was
      also observed when [Ca(2+)](i) was evaluated in the presence of 20 mM caffeine.
      After exposure to electromagnetic fields the basal [Ca(2+)](i) levels increased
      significantly from 143 +/- 46 nM to 278 +/- 125 nM. The increase was also evident
      after caffeine addition, but in cells treated with substance P and substance P +
      caffeine we observed a [Ca(2+)](i) decrease after exposure. When we substituted
      calcium-free medium for normal medium immediately before the [Ca(2+)](i)
      measurements, the [Ca(2+)](i) was similar to that measured in the presence of
      Ca(2+). In this case, after EMFs exposure of cells treated with substance P, the
      [Ca(2+)](i), measured without and with addition of caffeine, declined from 824 +/
      425 to 38 +/- 13 nM and from 1369 +/- 700 to 11 +/- 4 nM, respectively,
      indicating that electromagnetic fields act either on intracellular Ca(2+) stores
      or on the plasma membrane. Moreover the electromagnetic fields that affected
      [Ca(2+)](i) did not cause cell proliferation or cell death and the proliferation
      indexes remained unchanged after exposure.

PMID- 11568937
TI  - Green function method for calculating properties of static magnetic fields.
AB  - Given complete information about the normal component of a magnetic field in a
      plane, it is possible to directly calculate all aspects of the field at any point
      in a source-free, homogeneous volume above that plane. The magnetic scalar
      potential, the magnetic field, and its gradient have direct representations as
      integrals of the boundary data. This paper provides a Green function method for
      this problem, as well as examples of such calculations.

PMID- 11568938
TI  - Electromagnetic field of mobile phones affects visual event related potential in
      patients with narcolepsy.
AB  - The effects of the mobile phone (MP) electromagnetic fields on
      electroencephalography (EEG) and event-related potentials (ERP) were examined.
      With regard to the reported effects of MP on sleep, 22 patients with narcolepsy
      cataplexy were exposed or sham exposed for 45 min to the MP (900 MHz, specific
      absorption rate 0.06 W/kg) placed close to the right ear in a double blind study.
      There were no changes of the EEG recorded after the MP exposure. A subgroup of 17
      patients was studied on visual ERP recorded during the MP exposure. Using an
      adapted "odd-ball" paradigm, each patient was instructed to strike a key whenever
      rare target stimuli were presented. There were three variants of target stimuli
      (horizontal stripes in (i) left, (ii) right hemifields or (iii) whole field of
      the screen). The exposure enhanced the positivity of the ERP endogenous complex
      solely in response to target stimuli in the right hemifield of the screen (P <
      0.01). The reaction time was shortened by 20 ms in response to all target stimuli
      (P < 0.05). In conclusion, the electromagnetic field of MP may suppress the
      excessive sleepiness and improve performance while solving a monotonous cognitive
      task requiring sustained attention and vigilance.

PMID- 11568939
TI  - Monitoring a clinical trial with multiple hypotheses concerning the treatment
      effect on a single primary endpoint.
AB  - In a number of clinical trials there is interest in testing more than one
      hypothesis concerning the treatment effect on a single primary endpoint. For
      instance, a sponsor of a trial to demonstrate that a test treatment (T) is non
      inferior to an active control (R) may also be interested in showing that T is
      superior to R, if this is the case. Using the closed testing method for
      constructing tests of multiple hypotheses which control the multiple level of
      significance, we provide a framework for testing these hypotheses sequentially
      during a trial at pre-planned interim analyses.

PMID- 11568942
TI  - Correction of the P-value after multiple coding of an explanatory variable in
      logistic regression.
AB  - We propose a method and a program to determine a significance level for a series
      of codings of an explanatory variable in logistic regression. Dichotomous and Box
      Cox transformations are considered. Three methods of correcting the significance
      level are studied: the Bonferroni method; Efron's method, which uses the
      correlation between successive tests, and the exact calculation by numerical
      integration using all correlations. A simulation study has led to a strategy for
      the choice and number of the different codings of the variable. This method is
      illustrated using the data of a study of the relation between cholesterol and
      dementia.

PMID- 11568943
TI  - The continual reassessment method: comparison of Bayesian stopping rules for dose
      ranging studies.
AB  - The continual reassessment method (CRM) provides a Bayesian estimation of the
      maximum tolerated dose (MTD) in phase I clinical trials and is also used to
      estimate the minimal efficacy dose (MED) in phase II clinical trials. In this
      paper we propose Bayesian stopping rules for the CRM, based on either posterior
      or predictive probability distributions that can be applied sequentially during
      the trial. These rules aim at early detection of either the mis-choice of dose
      range or a prefixed gain in the point estimate or accuracy of estimated
      probability of response associated with the MTD (or MED). They were compared
      through a simulation study under six situations that could represent the
      underlying unknown dose-response (either toxicity or failure) relationship, in
      terms of sample size, probability of correct selection and bias of the response
      probability associated to the MTD (or MED). Our results show that the stopping
      rules act correctly, with early stopping by using the two first rules based on
      the posterior distribution when the actual underlying dose-response relationship
      is far from that initially supposed, while the rules based on predictive gain
      functions provide a discontinuation of inclusions whatever the actual dose
      response curve after 20 patients on average, that is, depending mostly on the
      accumulated data. The stopping rules were then applied to a data set from a dose
      ranging phase II clinical trial aiming at estimating the MED dose of midazolam in
      the sedation of infants during cardiac catheterization. All these findings
      suggest the early use of the two first rules to detect a mis-choice of dose
      range, while they confirm the requirement of including at least 20 patients at
      the same dose to reach an accurate estimate of MTD (MED). A two-stage design is
      under study.

PMID- 11568944
TI  - Can electronic medical images replace hard-copy film? Defining and testing the
      equivalence of diagnostic tests.
AB  - Electronic medical images are an efficient and convenient format in which to
      display, store and transmit radiographic information. Before electronic images
      can be used routinely to screen and diagnose patients, however, it must be shown
      that readers have the same diagnostic performance with this new format as
      traditional hard-copy film. Currently, there exist no suitable definitions of
      diagnostic equivalence. In this paper we propose two criteria for diagnostic
      equivalence. The first criterion ('population equivalence') considers the
      variability between and within readers, as well as the mean reader performance.
      This criterion is useful for most applications. The second criterion ('individual
      equivalence') involves a comparison of the test results for individual patients
      and is necessary when patients are followed radiographically over time. We
      present methods for testing both individual and population equivalence. The
      properties of the proposed methods are assessed in a Monte Carlo simulation
      study. Data from a mammography screening study is used to illustrate the proposed
      methods and compare them with results from more conventional methods of assessing
      equivalence and inter-procedure agreement.

PMID- 11568945
TI  - A hierarchical regression approach to meta-analysis of diagnostic test accuracy
      evaluations.
AB  - An important quality of meta-analytic models for research synthesis is their
      ability to account for both within- and between-study variability. Currently
      available meta-analytic approaches for studies of diagnostic test accuracy work
      primarily within a fixed-effects framework. In this paper we describe a
      hierarchical regression model for meta-analysis of studies reporting estimates of
      test sensitivity and specificity. The model allows more between- and within-study
      variability than fixed-effect approaches, by allowing both test stringency and
      test accuracy to vary across studies. It is also possible to examine the effects
      of study specific covariates. Estimates are computed using Markov Chain Monte
      Carlo simulation with publicly available software (BUGS). This estimation method
      allows flexibility in the choice of summary statistics. We demonstrate the
      advantages of this modelling approach using a recently published meta-analysis
      comparing three tests used to detect nodal metastasis of cervical cancer.

PMID- 11568946
TI  - Estimating the difference between differences: measurement of additive scale
      interaction for proportions.
AB  - A simple, effective closed-form method to calculate a confidence interval for the
      difference between two differences of proportions is proposed. The method is
      based on the Wilson score interval for the single proportion, and may be used to
      compare either unpaired or paired differences. It is equally applicable whether
      cell frequencies are large or small; and coverage properties are favourable. It
      is easily adapted to give a confidence interval for the treatment effect for a
      binary outcome in a two-period cross-over trial.

PMID- 11568947
TI  - Estimating equations for kappa statistics.
AB  - Kappa statistics are often used for measuring agreement or association. The
      original measure suggested by Cohen for use with nominal data has since been
      generalized in a number of ways, including the incorporation of weights,
      adaptation for use with more than one rater and the application to bivariate
      data. Each modification requires a new approximation to the standard error and
      these have usually been derived by the delta method. This paper illustrates the
      use of estimating equations for kappa which offer a unified approach to many
      previously considered situations and which is also applicable to more complex
      designs.

PMID- 11568948
TI  - Zero-inflated Poisson regression with random effects to evaluate an occupational
      injury prevention programme.
AB  - This study presents a zero-inflated Poisson regression model with random effects
      to evaluate a manual handling injury prevention strategy trialled within the
      cleaning services department of a 600 bed public hospital between 1992 and 1995.
      The hospital had been experiencing high annual rates of compensable injuries of
      which over 60 per cent were attributed to manual handling. The strategy employed
      Workplace Risk Assessment Teams (WRATS) that utilized a workplace risk
      identification, assessment and control approach to manual handling injury hazard
      reduction. The WRATS programme was an intervention trial, covering the 1988-1995
      financial years. In the course of compiling injury counts, it was found that the
      data exhibited an excess of zeros, in the context that the majority of cleaners
      did not suffer any injuries. This phenomenon is typical of data encountered in
      the occupational health discipline. We propose a zero-inflated random effects
      Poisson regression model to analyse such longitudinal count data with extra
      zeros. The WRATS intervention and other concomitant information on individual
      cleaners are considered as fixed effects in the model. The results provide
      statistical evidence showing the value of the WRATS programme. In addition, the
      methods can be applied to assess the effectiveness of intervention trials on
      populations at high risk of manual handling injury or indeed of injury from other
      hazards.

PMID- 11568949
TI  - Correlation coefficient estimation involving a left censored laboratory assay
      variable.
AB  - When assessing a correlation between two exposure or biological marker variables,
      one sometimes encounters the problem of indeterminate values for one of the
      variables due to an assay detection limit. In this event, investigators often
      report correlation coefficients computed after removing the pairs involving non
      detectable values, or after substituting some small constant for those values.
      These ad hoc practices can lead to bias in both point and confidence interval
      estimates of the true correlation coefficient. To address this issue, we consider
      two parametric techniques for estimating the correlation in the presence of left
      censoring for one of the variables. The first is a maximum likelihood approach,
      and the second is an adaptation of multiple imputation motivated primarily by
      potential benefits in confidence interval coverage. Both of the estimators
      studied reduce to the standard Pearson's correlation coefficient in the event of
      no censoring, and hence are valid in cases where this measure would be
      appropriate for the complete data. We assess these approaches empirically and
      contrast them with ad hoc methods for estimating the correlation between
      cervicovaginal human immunodeficiency virus (HIV) viral load measurements and
      CD4+ lymphocyte counts from HIV positive women enrolled in a clinical trial
      conducted in Bangkok, Thailand.

PMID- 11568950
TI  - Graphical model checking with correlated response data.
AB  - Correlated response data arise often in biomedical studies. The generalized
      estimation equation (GEE) approach is widely used in regression analysis for such
      data. However, there are few methods available to check the adequacy of
      regression models in GEE. In this paper, a graphical method is proposed based on
      Cook and Weisberg's marginal model plot. A bootstrap method is applied to obtain
      the reference band to assess statistical uncertainties in comparing two marginal
      mean functions. We also propose using the generalized additive model (GAM) in a
      similar fashion. The proposed two methods are easy to implement by taking
      advantage of existing smoothing and GAM softwares for independent data. The
      usefulness of the methodology is demonstrated through application to a correlated
      binary data set drawn from a clinical trial, the Lung Health Study.

PMID- 11568951
TI  - Event history graphs for censored survival data.
AB  - A compact graphical device for combining survival and time-varying covariate
      information is proposed. The proposed graph contains the Kaplan-Meier estimator
      for right-censored data and a simultaneous display of the behaviour of time
      dependent covariate(s) and the lifetime for each subject in the sample. The
      observed levels of time-dependent covariates are possibly subjected to an initial
      dimension reduction or smoothing step to produce a continuous covariate function.
      Values of this function are plotted on a horizontal bar for the length of the
      lifetime of the subject. Covariate information for censored data is also
      incorporated. The union of the horizontal bars forms the Kaplan-Meier estimator
      of the survival function. Our graphical method is implemented with a new S-plus
      function and demonstrated in several applications.

PMID- 11568952
TI  - Understanding neural networks using regression trees: an application to multiple
      myeloma survival data.
AB  - Neural networks are becoming very popular tools for analysing data. It is however
      quite difficult to understand the neural network output in terms of the original
      covariates or input variables. In this paper we provide, using readily available
      software, an easy way of understanding the output of the neural network using
      regression trees. We focus on the problem in the context of censored survival
      data for patients with multiple myeloma, where identifying groups of patients
      with different prognosis is an important aspect of clinical studies. The use of
      regression trees to help understand neural networks can be easily applied to
      uncensored situations.

PMID- 11568953
TI  - A weighted average likelihood ratio test for spatial clustering of disease.
AB  - We consider methods proposed for detecting localized spatial clustering. We
      propose a new test statistic, the weighted average likelihood ratio test, as an
      alternative to the spatial scan (maximum likelihood ratio) test statistic. Two
      different types of weights are considered. We propose an unbiased cluster
      selection criterion and evaluate the bias of the tests through simulation. We
      also examine the power of the tests through simulations and apply the methods to
      the well-known New York leukaemia data.

PMID- 11568955
TI  - A review and update on the practice of evaluating Miranda comprehension.
AB  - This article summarizes recent developments in constitutional law relevant to the
      Miranda warning. We describe the origins of the warning, concerns about the use
      of the Miranda warning, perspectives on the utility of the warning, and the
      relevance of the warning. We describe how the warning has changed over time,
      requirements for administering the warning, and procedures that police use in
      delivering the warning and obtaining confessions. We review case law relevant to
      "coerced" Miranda waivers and confessions, changes over time in the court's
      interpretation of what constitutes "coercion," use of the warning with special
      populations, and the recent focus in case law on individual factors that might
      impair Miranda comprehension. We review empirical research on factors associated
      with deficits in Miranda comprehension. We integrate case law rulings and
      empirical research into suggested approaches to forensic assessment of Miranda
      comprehension.

PMID- 11568956
TI  - A matter of life or death: special considerations and heightened practice
      standards in capital sentencing evaluations.
AB  - Mental health evaluations at capital sentencing represent a complex and
      specialized arena of practice. The moral culpability focus of capital sentencing
      is distinct from guilt-phase considerations of criminal responsibility, and has a
      specialized literature. Capital violence risk assessment is uniquely oriented to
      a prison context, relying on past adjustment to incarceration, as well as group
      statistical data specific to capital offenders and other inmate groups.
      Personality testing is a more complex consideration in capital sentencing
      evaluations. The implications of interviewing the defendant, as well as the
      parameters and documentation of an interview, make full disclosure and informed
      consent of particular importance. Defense- and prosecution-retained experts are
      subject to specific ethical vulnerabilities. These are examined in this paper
      through the lens of current professional standards.

PMID- 11568957
TI  - Psychological tests used in child custody evaluations.
AB  - Controversy has long surrounded the use of psychological testing in child custody
      evaluations. The present study explored the current status of psychological
      testing in these evaluations using a national survey of 198 psychologists.
      Findings revealed that participants viewed testing as one source among many for
      data collection, neither under- nor over-valuing its importance. Results also
      indicated that participants were more discriminating in their test selection,
      with a greater focus on objective assessment, particularly in the use of parent
      inventories and rating scales. These findings tend to negate much of the past
      criticism and reflect closer adherence to APA guidelines.

PMID- 11568958
TI  - Recent interview-based measures of competency to stand trial: a critical review
      augmented with research data.
AB  - Forensic experts are frequently asked to conduct competency-to-stand trial
      evaluations and address the substantive prongs propounded in Dusky v. United
      States (1960). In understanding its application to competency evaluations,
      alternative conceptualizations of Dusky are critically examined. With Dusky
      providing the conceptual framework, three interview-based competency measures are
      reviewed: the Georgia Court Competency Test (GCCT), the MacArthur Competence
      Assessment Tool-Criminal Adjudication (Mac-CAT-CA), and the Evaluation of
      Competency to Stand Trial-Revised (ECST-R). This review has a twin focus on
      reliability of each measure and its correspondence to Dusky prongs. The current
      review is augmented by new factor analytic data on the MacCAT-CA and ECST-R. The
      article concludes with specific recommendations for competency evaluations.

PMID- 11568959
TI  - Forensic and correctional applications of the personality assessment inventory.
AB  - The relative utility of psychological tests for addressing legal issues is an
      area of considerable debate in the field. Regardless of the merits of
      psychological testing, it is apparent that such instruments are used widely both
      to address specific psycholegal issues and to evaluate offender populations more
      generally. One instrument gaining prominence in terms of its use in both forensic
      and correctional settings is the Personality Assessment Inventory (PAI; Morey,
      1991), which was developed to assess various constructs relevant to clinical
      settings (e.g. psychopathology, response distortion, and personality traits).
      This paper reviews the psychometric properties of the PAI specifically in
      reference to its ability to assess factors relevant to forensic decision-making,
      as well as its utility to provide clinically relevant information about offender
      populations more generally.

PMID- 11568960
TI  - Preadolescent adjudicative competence: methodological considerations and
      recommendations for practice standards.
AB  - This article examines developmental and legal issues directed toward a downward
      age extension of forensic evaluation practice standards for preadolescent
      defendants whose competence is questioned. Existing research and practice
      standards were developed for cases involving adolescents and adults, but they
      lack sufficient application to evaluations of young children because of the ways
      in which legal parameters affect young children. We review practice implications
      of the legal role of "immaturity" for adjudicative competence, alterations of
      Dusky in some juvenile courts, and the role of parens patriae in competence
      hearings held in juvenile court. We examine competence abilities in a
      developmental framework. Examining practice standards is timely because
      adjudicative competence in preadolescent defendants has taken on recent
      significance. The last decade saw changes in the stringency of delinquency
      statutes, increased emphasis on adversarial approaches to juvenile proceedings,
      and a de-emphasis on rehabilitation and parens patriae protections. Statutory
      changes and increased referrals have heightened inquiry into the meaning of
      preadolescent adjudicative competence.

PMID- 11568961
TI  - The relationship between criminal charges, diagnoses, and psycholegal opinions
      among federal pretrial defendants.
AB  - This study analyzed data from 1710 criminal defendants referred by federal courts
      throughout the United States. We examined 12 categories of criminal charges with
      respect to diagnosed psychopathology and opinions related to competence to stand
      trial (CST) and criminal responsibility (CR) at the time of the alleged offense.
      Overall, 18% of the present sample were found to be incompetent to stand trial,
      while 12% were found to be not criminally responsible or 'insane.' In this study,
      crimes were associated with rates of psychopathology and rates of opinions
      regarding CST and CR. The findings of this study suggest that individuals who are
      charged with different crimes have different mental states and psychopathology
      and are therefore found to have differential rates of competence and sanity.

PMID- 11568962
TI  - What judges and lawyers think about the testimony of mental health experts: a
      survey of the courts and bar.
AB  - The testimony of mental health experts is often important evidence considered by
      criminal courts in determining issues arising throughout the adjudicative
      process, but not all evidence provided by experts is equally valid or probative.
      Using a hypothetical insanity defense case, we compared the preferences of
      Virginia judges, prosecutors, and defense attorneys for different types of
      forensic mental health evidence, including descriptive and diagnostic testimony,
      testimony about relevant research and actuarial data, and ultimate issue
      testimony. In addition, we determined their preferences for different types of
      mental health professionals. Four key findings emerged. First, many participants
      preferred that psychiatrists, rather than psychologists or other mental health
      professionals, conduct forensic evaluations for the court. Second, while
      participants were interested in most types of mental health evidence, they were
      primarily interested in clinical diagnosis, followed by an analysis of whether
      the condition met the relevant legal threshold, and an ultimate opinion on the
      legal issue. Third, participants were less interested in research or actuarial
      evidence. Fourth, participants differed in their evidentiary preferences in ways
      that reflect their respective roles in the adversary system. The findings suggest
      that while courts and attorneys find traditional clinical testimony useful in
      criminal cases, they also favor ultimate issue testimony, and view research data
      or statistically based information as less helpful. Mental health professionals
      should consider how to educate the courts and bar about the dangers inherent in
      over-reliance on the conclusory legal testimony of mental health experts, the
      utility of scientific data as such information becomes more routinely introduced
      as evidence at trial, and the expertise available from various mental health
      professionals.

PMID- 11568963
TI  - Spatial patterns of serial murder: an analysis of disposal site location choice.
AB  - Although the murders committed by serial killers may not be considered rational,
      there is growing evidence that the locations in which they commit their crimes
      may be guided by an implicit, if limited rationality. The hypothesized logic of
      disposal site choice of serial killers led to predictions that (a) their criminal
      domains would be around their home base and relate to familiar travel distances,
      (b) they would have a size that was characteristic of each offender, (c) the
      distribution would be biased towards other non-criminal activities, and (d) the
      size of the domains would increase over time. Examination of the geographical
      distribution of the sites at which 126 US and 29 UK serial killers disposed of
      their victims' bodies supported all four hypotheses. It was found that rational
      choice and routine activity models of criminal behavior could explain the spatial
      choices of serial murderers. It was concluded that the locations at which serial
      killers dispose of their victims' bodies reflect the inherent logic of the
      choices that underlie their predatory activities.

PMID- 11568964
TI  - Leucine transport in membrane vesicles from Chironomus riparius larvae displays a
      melange of crown-group features.
AB  - Leucine uptake into membrane vesicles from larvae of the midge Chironomus
      riparius was studied. The membrane preparation was highly enriched in typical
      brush border membrane enzymes and depleted of other membrane contaminants. In the
      absence of cations, there was a stereospecific uptake of l-leucine, which
      exhibited saturation kinetics. Parameters were determined both at neutral (Km 33
      +/- 5 microM and Vmax 22.6 +/- 6.8 pmol/7s/mg protein) and alkaline (Km 46 +/- 5
      microM and Vmax 15.5 +/- 2.5 pmol/7s/mg protein) pH values. At alkaline pH,
      external sodium increased the affinity for leucine (Km 17 +/- 1 microM) and the
      maximal uptake rate (Vmax 74.0 +/- 12.5 pmol/7s/mg protein). Stimulation of
      leucine uptake by external alkaline pH agreed with lumen pH measurements in vivo.
      Competition experiments indicated that at alkaline pH, the transport system
      readily accepts most L-amino acids, including branched, unbranched, and alpha
      methylated amino acids, histidine and lysine, but has a low affinity for
      phenylalanine, beta-amino acids, and N-methylated amino acids. At neutral pH, the
      transport has a decreased affinity for lysine, glycine, and alpha-methylleucine.
      Taken together, these data are consistent with the presence in midges of two
      distinct leucine transport systems, which combine characters of the lepidopteran
      amino acid transport system and of the sodium-dependent system from lower
      neopterans.

PMID- 11568965
TI  - Hydrogen peroxide detoxification in the midgut of the blood-sucking insect,
      Rhodnius prolixus.
AB  - Here we investigated H2O2 production and detoxification in the hematophagous
      hemiptera, Rhodnius prolixus. Superoxide dismutase (SOD) catalyzes the
      dismutation of superoxide radical (O2-). This reaction produces hydrogen
      peroxide, which is scavenged by antioxidant enzymes such as catalase (CAT). SOD
      and CAT activities were found in all tissues studied, being highest in the
      midgut. CAT was dose-dependently inhibited in vivo by injections of 3-amino-1,2,4
      triazole (AT). Insects treated with AT showed a twofold increase in H2O2 levels.
      Injection of DL-buthionine-[S, R]-sulfoximine (BSO), an inhibitor of glutathione
      synthesis, also resulted in a fourfold increase in H2O2, together with
      stimulation of CAT activity. Simultaneous administration of both AT and BSO had a
      synergistic effect on midgut H2O2 content. Taken all together, our results
      suggest that CAT and glutathione-dependent mechanisms cooperate to control H2O2
      concentration in the midgut cell and prevent hydroxyl radical generation by
      Fenton reaction in this tissue.

PMID- 11568966
TI  - Molecular evidence for two vitellogenin genes and processing of vitellogenins in
      the American cockroach, Periplaneta americana.
AB  - The American cockroach, Periplaneta americana has two vitellins (Vn1 and Vn2) and
      corresponding vitellogenins (Vg1 and Vg2). Vns/Vgs were separated on the SDS-PAGE
      as three major polypeptide bands [170, 100 (multisubunits), and 50 kD] and a
      minor polypeptide band (150 kD) both in the egg (mature terminal oocyte) extract
      and in the female hemolymph. We previously cloned one Vg (Vg1) cDNA and showed
      that the 170-kD polypeptide originated from the C-terminus of the Vg1. In the
      present study, we cloned the other Vg (Vg2) cDNA. It is 5,826 bp long encoding
      1,876 amino acid residues (including 16 residues for putative signal peptide) in
      a single ORF. The deduced amino acid sequences of both Vgs (Vg1 and Vg2) of P.
      americana showed 30% identity. The GL/ICG motif is followed by eight cysteine
      residues at conserved locations near the C-terminal and the DGXR motif starts 18
      residues upstream of the GL/ICG motif. The chemically determined N-terminal amino
      acid sequences of the 150-kD and of the 50-kD polypeptides matched exactly with
      each other and with the deduced N-terminal amino acid sequence of the Vg2 cDNA.
      The pattern of processing in P. americana Vns/Vgs is discussed.

PMID- 11568967
TI  - Cytoskeleton elements mediate the inhibition of the (Na++K+)atpase activity by
      PKC in Rhodnius prolixus malpighian tubules during hyperosmotic shock.
AB  - In a previous paper, we observed that the specific activity of (Na++K+)ATPase of
      the isolated Malpighian tubules from Rhodnius prolixus is inhibited by protein
      kinase C (PKC) during hyperosmotic shock [Arenstein et al., J Membr Biol 146:47
      57 [1995]; Caruso-Neves et al., Z Naturforsch 53c:911-917 [1998]). In the present
      paper, we study the involvement of the cytoskeleton in this process using
      isolated Malpighian tubules of Rhodnius prolixus. We observed that pre-incubation
      of the Malpighian tubule cells in hyperosmotic media decreases the specific
      activity of (Na++K+)ATPase by 90%. This effect was completely reversed when
      colchicine, which disrupts microtubules, or cytochalasin B, an inhibitor of actin
      microfilament polymerization, were added to the media in a dose-dependent manner.
      The maximal reversion was obtained with colchicine 7.0 microM or cytochalasin B
      5.0 microM. The simultaneous addition of sphingosine 50 ng/mL, an inhibitor of
      PKC, to 10 microM colchicine or 5 microM cytochalasin B, in hyperosmotic media,
      did not change the stimulatory effect of these drugs on the specific activity of
      (Na++K+)ATPase. On the other hand, the co-incubation of TPA 20 ng/mL, an
      activator of PKC, to colchicine or cytochalasin B within hyperosmotic media,
      abolished the stimulatory effect of these drugs on the specific activity of
      (Na++K+)ATPase to a similar extent as hyperosmotic shock. These results suggest
      that inhibition of the (Na++K+)ATPase of the isolated Malpighian tubules from
      Rhodnius prolixus by PKC during hyperosmotic shock is mediated by cytoskeletal
      elements.

PMID- 11568968
TI  - Effects of calcium channel antagonists on the corpora allata of adult male loreyi
      leafworm Mythimna loreyi: juvenile hormone acids release and intracellular
      calcium level.
AB  - The effects of voltage-dependent calcium channel (VDCC) antagonists and the non
      specific calcium channel antagonists on both juvenile hormone acids (JHA) release
      and cytosolic free calcium concentration ([Ca2+]i) are investigated in the
      corpora allata (CA) of the adult males loreyi leafworm Mythimna loreyi. The VDCC
      antagonists used in this study are: the L-type antagonists diltiazem, nifedipine,
      and verapamil, the N-type antagonist omega-Conotoxin (CgTx) GVIA, the N- and P/Q
      type antagonist omega-CgTx MVIIC, and the T-type antagonist amiloride. The non
      specific calcium channel antagonists used in this study were cadmium (Cd2+),
      cobalt (Co2+), nickle (Ni2+), and lanthanum (La3+). The results show that both
      the DHPs-sensitive L-type antagonist nifedipine and the N-type antagonist omega
      CgTx GVIA were able to inhibit JHA release, but only omega-CgTx GVIA was able to
      reduce the [Ca2+]i. Among the non-specific calcium channel antagonists, Cd2+ is
      the most potent in reducing JHA release but without obvious effect on the
      [Ca2+]i, La3+ significantly increases the [Ca2+]i but without effect on JHA
      release.

PMID- 11568969
TI  - Nitric oxide: an unconventional messenger in the nervous system of an
      orthopteroid insect.
AB  - Nitric oxide (NO) is a membrane-permeant messenger molecule generated from the
      amino acid L-arginine. NO can activate soluble guanylyl cyclase leading to the
      formation of cyclic GMP (cGMP) in target cells. In the nervous system, NO/cGMP
      signalling is thought to play essential roles in synaptic plasticity during
      development and also in the mature animal. This paper examines biochemical, cell
      biological, and physiological investigations of NO/cGMP signalling in the nervous
      system of the locust, a commonly used neurobiological preparation. Biochemical
      investigations suggest that an identical enzyme is responsible for both NO
      synthase (NOS) and NADPH-diaphorase activity after tissue fixation.
      Immunocytochemical staining of an olfactory center in the locust brain shows that
      NOS-immunoreactivity colocalizes with NADPH-diaphorase at the cellular level. The
      cytochemical staining of NO donor and target cells in adult animals suggests
      functions in olfaction, vision, and sensorimotor integration. During development,
      NO is implicated in axonal outgrowth and synaptogenesis. The cellular
      distribution of NO-responsive cells in neural circuits reflects potential
      functions of NO as a retrograde synaptic messenger, as an intracellular
      messenger, and as a lateral diffusible messenger independent of conventional
      synaptic connectivity.

PMID- 11568970
TI  - Incidence and effects of Ha-ras codon 12 G-->A transition mutations in
      preneoplastic lesions induced by N-nitrosomethylbenzylamine in the rat esophagus.
AB  - N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis is an
      important model for squamous cell carcinoma of the human esophagus. In this
      model, previous studies have shown that the GGA-->GAA Ha-ras codon 12 mutation is
      present in the majority of papillomas. No other Ha-ras mutation has been
      identified. Studies using other models of chemical carcinogenesis suggest that Ha
      ras activation has a critical role during tumor initiation. We have used laser
      capture microdissection and polymerase chain reaction-restriction fragment length
      polymorphism analysis to study the role of codon 12 Ha-ras mutation at various
      stages of tumor development in the rat esophagus. Our results indicate that Ha
      ras mutation was present infrequently (4.3%) in premalignant lesions. The
      incidence of Ha-ras mutation was high in papillomas (57.1%), however, and 50% of
      papillomas expressed mutant Ha-ras RNA message. Additionally, there was a linear
      trend correlating increased incidence of Ha-ras mutation with later papilloma
      stage. These data suggest the role of ras activation later in neoplastic
      development. To evaluate the potential mechanism of action by which Ha-ras
      contributes to promotion and progression in this model, we compared mRNA
      expression of cyclin D1 and p27 in Ha-ras mutant and Ha-ras normal papillomas. We
      found no differences in mRNA expression of either cyclin D1 or p27 between these
      two papilloma populations. Our data suggest an important paradigm shift for the
      role of ras mutations in this model of chemical carcinogenesis, indicating a
      functional role of Ha-ras activation in promotion/progression and not in the
      initiation phase of NMBA-induced papillomagenesis.

PMID- 11568971
TI  - Resistance of primary cultured mouse hepatic tumor cells to cellular senescence
      despite expression of p16(Ink4a), p19(Arf), p53, and p21(Waf1/Cip1).
AB  - Primary cultured mouse hepatic cells become senescent within a short period,
      although rare cells form colonies from which continuously proliferating cell
      lines can be established. In contrast, hepatic tumor (HT) cells show little
      senescence and higher colony-forming capacity. To assess this difference, we
      investigated p16(Ink4a)/p19(Arf)/p53/p21(Waf1/Cip1) expression in primary normal
      and HT cells, together with cell lines established from both. In primary normal
      cells, p16(Ink4a)/p19(Arf) were expressed only in association with senescence and
      disappeared at later stages of colony formation. In contrast, primary HT cells
      showed sustained p16(Ink4a)/p19(Arf) expression from the beginning. No
      p16(Ink4a)/p19(Arf) alterations, such as deletion, mutations, or
      hypermethylation, were detected in the primary HT cells, although most cell lines
      derived from either normal or HT cell colonies lost p16(Ink4a) or p19(Arf)
      expression owing to hypermethylation or homozygous deletion of
      p16(Ink4a)/p19(Arf). On the other hand, primary normal and HT cells and most cell
      lines showed constitutively elevated expression of p53/p21(Waf1/Cip1), with a
      further increment after ultraviolet ir-radiation, indicating a functionally
      normal p53 pathway. These results indicate that primary HT cells are resistant to
      senescence despite retaining p16(Ink4a)/p19(Arf)/p53/p21(Waf1/Cip1) expression
      and that loss of p16(Ink4a)/p19(Arf) function is associated only with
      establishment of the cell lines.

PMID- 11568972
TI  - CpG methylation of promoter region inactivates E-cadherin gene in renal cell
      carcinoma.
AB  - CpG methylation in the promoter region has been shown to be important in the
      regulation of genes implicated in malignant transformation. The present study was
      designed to test the hypothesis that CpG methylation of the promoter region of
      the E-cadherin gene may inactivate its expression in renal cell carcinoma. To
      test this hypothesis, five kidney cancer cell lines and 34 microdissected renal
      cell carcinoma samples were analyzed for gene and protein expression by reverse
      transcription-polymerase chain reaction and immunohistochemistry, respectively.
      CpG methylation in the promoter regions of the E-cadherin gene was analyzed by
      the sodium bisulfite genome sequencing technique. Our results show that all
      normal renal tissue expressed the E-cadherin gene and protein. Of the renal
      cancer tissues analyzed, 67% (23 of 34) lacked E-cadherin expression, with an
      associated increase in methylation, compared with normal tissue. E-cadherin gene
      promoter was methylated in all renal cancer cell lines and was accompanied by a
      loss of E-cadherin gene and protein expression. The treatment of renal cancer
      cell lines with the demethylating agent 5-aza-2'-deoxycytidine restored E
      cadherin mRNA expression in all renal cancer cell lines. This is the first report
      that shows inactivation of the E-cadherin gene and protein in renal cell
      carcinoma through CpG hypermethylation in the promoter region of this gene. The
      results of these experiments may contribute to an understanding of the role of E
      cadherin inactivation in renal cell carcinoma.

PMID- 11568973
TI  - Gene expression profile in BALB/c-3T3 cells transformed with beryllium sulfate.
AB  - Differential gene expression was studied to understand the potential molecular
      mechanism responsible for cell transformation and tumorigenesis induced by
      beryllium. Cell lines were derived from tumors developed in nude mice injected
      subcutaneously with BALB/c-3T3 cells morphologically transformed with beryllium
      sulfate. Using the Atlas mouse 1.2 cDNA expression microarray, the expression
      profiles of 1176 genes, belonging to several different functional categories,
      were studied in the tumor cells as well as in the nontransformed control cells.
      Expression of 18 genes belonging to two functional groups was found to be
      consistently and reproducibly different (at least twofold) in the tumor cells
      compared with the control cells. The functional groups and the differentially
      expressed genes are as follows: The cancer-related genes (nine genes) were the
      ets-related transcription factor activated by ras, colony-stimulating factor, A
      myb, sky, cot1, c-fos, c-jun, c-myc, and R-ras proto-oncogenes. The DNA
      synthesis, repair, and recombination genes (nine genes) were the DNA replication
      licensing factor MCM4, the DNA replication licensing factor MCM5, the DNA
      mismatch repair gene PMS2, the DNA excision repair gene, the DNA mismatch repair
      gene MSH2, the ultraviolet excision repair gene Rad23 DNA ligase 1, Rad51, and
      Rad52. The differential gene expression profile was confirmed with reverse
      transcription-polymerase chain reaction using primers specific for the
      differentially expressed genes. In general, expression of the cancer-related
      genes was upregulated, while expression of genes involved in DNA synthesis,
      repair, and recombination was downregulated in the tumor cells compared with the
      control cells. Using c-fos and c-jun, two of the differentially expressed genes,
      as model genes, we have found that in the nontransformed BALB/c-3T3 cells, the
      beryllium-induced transcriptional activation of these genes was dependent on
      pathways of protein kinase C and mitogen-activated protein kinase and independent
      of reactive oxygen species. These results indicate that beryllium-induced cell
      transformation and tumorigenesis are accompanied by and are possibly a product of
      alterations in expression of genes related to cancer and to DNA synthesis,
      repair, and recombination.

PMID- 11568974
TI  - Hypermethylation of the tumor necrosis factor receptor superfamily 6 (APT1, Fas,
      CD95/Apo-1) gene promoter at rel/nuclear factor kappaB sites in prostatic
      carcinoma.
AB  - DNA hypermethylation of CpG-rich promoter sequences is associated with tumor
      suppressor gene inactivation in many human cancers, notably in carcinoma of the
      prostate and the urinary bladder. Recently, the mouse homologue of the tumor
      necrosis factor receptor superfamily 6 (TNFRSF6) gene was reported to be
      inactivated by DNA methylation in various cell types. The Fas (CD95, Apo-1)
      protein encoded by the TNFRSF6 gene is an important mediator of apoptosis, which
      also is downregulated in different types of human carcinoma. We therefore
      investigated the methylation of the TNFRSF6 promoter in prostatic and bladder
      carcinomas and cell lines. In a restriction enzyme polymerase chain reaction
      assay, four of 32 prostatic carcinomas and three of 15 advanced bladder
      carcinomas showed evidence of hypermethylation at the rel/nuclear factor kappaB
      (NFkappaB) binding sites essential for promoter activity. The DU145 cell line
      derived from a metastasis of a prostate carcinoma also displayed hypermethylation
      in this assay, which was confirmed by bisulfite sequencing. Treatment of DU145
      cells with the methylation inhibitor deoxyazacytidine slightly increased Fas
      protein expression, as detected by flow cytometry analysis. In vitro methylation
      of the TNFRSF6 promoter at the rel/NFkappaB sites completely abolished its
      activity. Thus, although the TNFRSF6 gene can be inactivated efficiently by DNA
      methylation, hypermethylation occurs neither frequently nor extensively in human
      carcinomas and appears to play a limited role in downregulation of Fas
      expression.

PMID- 11568975
TI  - Characterization of a novel gene, STAG1/PMEPA1, upregulated in renal cell
      carcinoma and other solid tumors.
AB  - Using differential display-polymerase chain reaction, we identified a novel gene
      sequence, designated solid tumor-associated gene 1 (STAG1), that is upregulated
      in renal cell carcinoma (RCC). The full-length cDNA (4839 bp) encompassed the
      recently reported androgen-regulated prostatic cDNA PMEPA1, and so we refer to
      this gene as STAG1/PMEPA1. Two STAG1/PMEPA1 mRNA transcripts of approximately 2.7
      and 5 kb, with identical coding regions but variant 3' untranslated regions, were
      predominantly expressed in normal prostate tissue and at lower levels in the
      ovary. The expression of this gene was upregulated in 87% of RCC samples and also
      was upregulated in stomach and rectal adenocarcinomas. In contrast, STAG1/PMEPA1
      expression was barely detectable in leukemia and lymphoma samples. Analysis of
      expressed sequence tag databases showed that STAG1/PMEPA1 also was expressed in
      pancreatic, endometrial, and prostatic adenocarcinomas. The STAG1/PMEPA1 cDNA
      encodes a 287-amino-acid protein containing a putative transmembrane domain and
      motifs that suggest that it may bind src homology 3- and tryptophan tryptophan
      domain-containing proteins. This protein shows 67% identity to the protein
      encoded by the chromosome 18 open reading frame 1 gene. Translation of
      STAG1/PMEPA1 mRNA in vitro showed two products of 36 and 39 kDa, respectively,
      suggesting that translation may initiate at more than one site. Comparison to
      genomic clones showed that STAG1/PMEPA1 was located on chromosome 20q13 between
      microsatellite markers D20S183 and D20S173 and spanned four exons and three
      introns. The upregulation of this gene in several solid tumors indicated that it
      may play an important role in tumorigenesis.

PMID- 11568976
TI  - The psychobiology of sleep and major depression.

PMID- 11568977
TI  - Sleep disturbances and mood disorders: an epidemiologic perspective.
AB  - Epidemiologic studies of sleep disturbances and mood disorders that may provide
      more valid estimates of associations between these two conditions than clinical
      samples due to differential use of health care services. Increasing uniformity of
      questionnaires to assess sleep disturbances has decreased the variance in
      estimates of insomnia and hypersomnia within community samples. Women are more
      likely to report insomnia than men in every age group. There appear to be no
      clear racial or ethnic differences in rates of insomnia or hypersomnia. Several
      community-based studies have found that sleep disturbances are powerful risk
      factors for the development of new episodes of major depression in the following
      year. Individuals who report insomnia or poor quality sleep may be at higher risk
      for depression throughout their lifetime. Epidemiologic studies will be useful
      for developing the long-term perspective on the natural history of sleep
      disturbances and mood disorders and the consequences of treatment.

PMID- 11568978
TI  - Treatment of insomnia in patients with mood disorders.
AB  - Mood disorders and chronic insomnia share complex theoretical and clinical
      relationships. This article reviews the subjective symptoms and polysomnographic
      findings of subjects with mood and insomnia syndromes. The polysomnographic
      findings reviewed include macro-architectural and micro-architectural data.
      Various treatments of patients with insomnia and mood disorders will be
      presented, including both behavioral and pharmacological interventions.

PMID- 11568979
TI  - Depression, sleep physiology, and antidepressant drugs.
AB  - This review summarizes current findings regarding effects of antidepressant
      compounds on sleep architecture and interprets their clinical relevance. Effects
      of the major classes of antidepressant drugs on sleep properties are presented,
      with the antidepressant compounds organized into categories based primarily on
      their putative mechanism of action. The majority of antidepressant compounds,
      across several different categories, exhibit robust suppression of REM sleep.
      Others, such as bupropion and nefazodone, lack REM suppressant effects. Such
      findings support the idea that critical neurochemical mechanisms involved in the
      regulation of discrete sleep stages can be elucidated by means of
      polysomnographic investigations utilizing pharmacologically targeted agents.
      Clinicians have appreciated the importance of antidepressant drug effects on
      sleep when considering therapeutic options for patients. While such decisions in
      the past were based on empirical observations, an increasing amount of
      information regarding specific effects of different antidepressant drugs on sleep
      continuity and sleep architecture is available. Thus, clinicians may choose to
      consider profiles of sleep effects for different antidepressant drugs in the
      initial selection of an antidepressant compound.

PMID- 11568980
TI  - Potential mechanisms of the sleep therapies for depression.
AB  - Sleep deprivation for one night has been investigated as a treatment for
      depression since the first publications describing its antidepressant properties
      almost 30 years ago [Pflug and Tolle, 1971: Int Pharmacopsychiatry 6:187-196]. It
      remains a field of active research. It is the only intervention consistently
      demonstrated to produce next-day antidepressant results. This makes sleep
      deprivation an exciting and unique tool to study the pathophysiology of
      depressive disorders and to formulate targets for novel antidepressant agents.
      Importantly, it is also an effective, but underused, clinical treatment for
      unipolar and bipolar depression.

PMID- 11568981
TI  - Sleep deprivation as a model experimental antidepressant treatment: findings from
      functional brain imaging.
AB  - This paper reviews the functional brain imaging studies in depressed patients
      treated with sleep deprivation. Sleep deprivation is an excellent experimental
      model of antidepressant treatments which offer new opportunities to understand
      the basic neural mechanisms. Its antidepressant effects are efficacious and
      rapid; sleep deprivation is easy to administer, inexpensive, and relatively safe;
      it can be studied in patients, normal controls, and animals; and it may lead to
      new treatments and new paradigms for antidepressant therapies. Seven published
      papers, coming from five different research centers, using either positron
      emission tomography (PET) with 18fluorodeoxyglucose (FDG) or single photon
      emission computerized tomography (SPECT) with Technetium-99-bexamethyl
      propyleneamine oxime (HMPAO) have relatively consistent findings. First, before
      sleep deprivation, responders have significantly elevated metabolism compared
      with non-responders, and usually the normal controls, in the orbital medial
      prefrontal cortex, and especially in the ventral portions of the anterior
      cingulate cortex. Secondly, after sleep deprivation, these hyperactive areas
      normalize in the responders. The magnitude of the clinical improvement was
      significantly correlated with decreased local glucose metabolic rate or cerebral
      blood flow in three studies. The results are consistent with some but not all
      functional brain imaging studies of antidepressant medications in depressed
      patients. Finally, a SPECT study using a radioactively labeled D2 receptor
      antagonist suggests that the antidepressant benefits of sleep deprivation are
      correlated with endogenous release of dopamine.

PMID- 11568982
TI  - Three-dimensional planning and simulation of hip operations and computer-assisted
      construction of endoprostheses in bone tumor surgery.
AB  - OBJECTIVE: This article presents the VIRTOPS (VIRTual Operation Planning in
      Orthopaedic Surgery) software system for virtual preoperative planning and
      simulation of hip operations. The system is applied to simulate the
      endoprosthetic reconstruction of the hip joint with hemipelvic replacement, and
      supports the individual design of anatomically adaptable, modular prostheses in
      bone tumor surgery. The virtual planning of the operation and the construction of
      the individual implant are supported by virtual reality techniques. The central
      step of the operation planning procedure, the placement of the cutting plane in
      the hip bone, depends strongly on the tumor's position. Segmentation of the tumor
      and the bones in MR and CT data, as well as fusion of MR and CT image sequences,
      is necessary to visualize the tumor's position within the hip bone. MATERIALS AND
      METHODS: Three-dimensional models of the patient's hip are generated based on CT
      image data. A ROI-based segmentation algorithm enables the separation of the bone
      tumor in multispectral MR image sequences. A special registration method using
      segmentation results has been developed to transfer CT and MR data into one
      common coordinate system. During the 3D planning process, the surgeon simulates
      the operation and defines the position and geometry of the custom-made
      endoprosthesis. Stereoscopic visualization and 3D input devices facilitate
      navigation and 3D interaction in the virtual environment. Special visualization
      techniques such as texture mapping, color coding of quantitative parameters, and
      transparency support the determination of the correct position and geometry of
      the prosthesis. RESULTS AND CONCLUSIONS: The VIRTOPS system enables the complete
      virtual planning of hip operations with endoprosthetic reconstruction, as well as
      the optimal placement and design of endoprostheses. After the registration and
      segmentation of CT and MR data, 3D visualizations of the tumor within the bone
      are generated to support the surgeon during the planning procedure. In the
      virtual planning environment, individually adapted endoprostheses can be
      constructed without the need to generate expensive solid 3D models. Furthermore,
      different operation strategies can be compared easily. Three-dimensional images
      and digital movies generated during the virtual operation planning can be used
      for case documentation and patient information purposes.

PMID- 11568983
TI  - New virtual system for planning of neuroendoscopic interventions.
AB  - OBJECTIVE: The demands on virtual planning systems are increasing, particularly
      for technically pretentious surgical interventions such as intracranial
      endoscopy. In this article, a new virtual system for neuroendoscopy (VIVENDI) is
      presented. The main purpose of this system is to provide support for planning and
      training in neuroendoscopic interventions. MATERIALS AND METHODS: The software is
      applied for virtual endoscopic visualization of three-dimensional magnetic
      resonance datasets, using a clinical magnetic resonance scanner. Rendering is
      performed on a Hewlett-Packard UNIX workstation. RESULTS: Virtual endoscopy
      provides a three-dimensional view of the cerebral ventricles, with good
      visualization of anatomic details. The rendering system used allows the
      generation of fly-through sequences for the entire ventricular system in real
      time. Navigation is controlled by mouse movements, and the visualization of the
      computer-generated intraventricular spaces is adapted to the characteristics of
      the optical endoscope. CONCLUSIONS: The presented virtual neuroendoscopy system
      is a promising tool for planning and training in neuroendoscopic procedures. It
      enables these procedures to be simulated prior to surgery based on the patient's
      individual anatomy.

PMID- 11568984
TI  - A full 3D-navigation system in a suitcase.
AB  - OBJECTIVE: To reduce the impact of contemporary 3D-navigation systems on the
      environment of typical otorhinolaryngologic operating rooms, we demonstrate that
      a transfer of navigation software to modern high-power notebook computers is
      feasible and results in a practicable way to provide positional information to a
      surgeon intraoperatively. MATERIALS AND METHODS: The ARTMA Virtual Patient System
      has been implemented on a Macintosh PowerBook G3 and, in connection with the
      Polhemus FASTRAK digitizer, provides intraoperative positional information during
      endoscopic endonasal surgery. RESULTS: Satisfactory intraoperative navigation has
      been realized in two- and three-dimensional medical image data sets (i.e., X-ray,
      ultrasound images, CT, and MR) and live video. CONCLUSIONS: This proof-of-concept
      study demonstrates that acceptable ergonomics and excellent performance of the
      system can be achieved with contemporary high-end notebook computers.

PMID- 11568985
TI  - Real-time optical coherence tomography for minimally invasive imaging of prostate
      ablation.
AB  - OBJECTIVE: Numerous ablation techniques have been developed to alleviate urethral
      obstruction and improve urodynamics in benign prostatic hyperplasia. Most
      techniques, however, rely on visual observation of surface changes for ablation
      end points. The feasibility of using real-time optical coherence tomography (OCT)
      for minimally invasive imaging to guide and monitor prostate resection is
      demonstrated with representative techniques of laser and radiofrequency ablation.
      Empiric comparisons of ablation dynamics are made, and the use of OCT as a high
      resolution, subsurface modality for image guidance is evaluated. MATERIALS AND
      METHODS: Optical coherence tomography is a high-resolution, high-speed near
      infrared imaging technique analogous to ultrasound imaging, except that
      reflections of light are detected rather than sound. High-speed OCT is used to
      image the dynamic process of laser and radiofrequency ablation of in vitro human
      prostate tissue. OCT images of ablation sites are compared with corresponding
      histology. RESULTS: Based on comparisons between OCT images and corresponding
      histology, OCT imaged transurethral prostate tissue morphology, including
      urethral sinuses and submucosal glands. Real-time OCT imaging provided rapid
      feedback and control of ablation dynamics. The compact and portable OCT
      technology is amenable to minimally invasive beam-delivery devices. CONCLUSIONS:
      Optical coherence tomography offers a minimally invasive means of assessing
      transurethral prostate morphology. Real-time OCT has the potential to provide
      image guidance of prostate resection for many of the existing surgical treatments
      directed at alleviating urethral obstruction associated with benign prostatic
      hyperplasia.

PMID- 11568986
TI  - A fast impingement detection algorithm for computer-aided orthopedic surgery.
AB  - OBJECTIVE: For simulation of computer-aided orthopedic interventions, the
      detection of impingement between parts of the patient's anatomy and/or implants
      is often of key importance. The impingement (collision) detection methods used in
      the existing literature seem to be unsuitable for two reasons. First, a
      polyhedral approximation of an anatomical model is not appropriate because
      medical images are quite irregular and are geometrically complex. Second,
      geometric and temporal coherences are not always available, because only the
      final results may be of interest. This article describes the development of a
      fast and accurate impingement detection algorithm for medical applications.
      MATERIALS AND METHODS: The presented algorithm takes implicit object models from
      reconstructions of anatomical CT data that represent complicated anatomical
      structures. To speed up the detection procedure, a lookup table and a linear
      transform are used so that searching for impingement between any two objects
      becomes a problem of calculating spatial indices and checking the lookup table.
      RESULTS: For any given transformation, the algorithm could perform impingement
      detection of two objects within 0.1 s on a 167 MHz Sun UltraSPARC1 workstation.
      Experimental results concerning accuracy, reliability and speed are given for a
      phantom and for a patient's data set. CONCLUSIONS: This algorithm provides a
      general-purpose impingement detection method in the sense that objects can be of
      any shape, and it can be extended to any number of objects in the scene.

PMID- 11568987
TI  - Stimulation of lung growth in fetuses with lung hypoplasia leads to altered
      postnatal lung structure in sheep.
AB  - Increased lung expansion in the fetus stimulates lung growth and is being trialed
      clinically to reverse severe fetal lung hypoplasia. Our aim was to examine the
      effects of increased fetal lung expansion in the presence of lung hypoplasia on
      lung structure in sheep at term and 8 weeks after birth. Lung hypoplasia was
      induced in 15 fetal sheep by continuous drainage of tracheal fluid, commencing at
      approximately 113 days of gestation (term, approximately 148 days). In 10 of
      these fetuses, tracheal obstruction (TO) was performed from 137-147 days of
      gestation (treated lung hypoplasia, TLH), while lung liquid drainage continued
      until term in the remaining 5 fetuses (untreated lung hypoplasia, ULH). Lung
      tissues were obtained from 5 TLH, 5 ULH, and 5 control lambs at birth, and from 5
      TLH and 5 control lambs at 8 weeks after birth. At birth, alveolar number,
      surface area, and interalveolar wall thickness were not different between TLH and
      control lambs, whereas airspace diameter was greater in TLH lambs (72.7 +/- 3.0
      microm) than in controls (58.4 +/- 4.3 microm). Diameters of airspaces were not
      different between ULH and control lambs; however, alveolar numbers and surface
      area were reduced, while interalveolar wall thickness was increased in ULH lambs
      compared to controls. At 8 weeks after birth, alveolar number (928.0 +/- 66.1 x
      10(6)) and surface area (30.3 +/- 2.2 m(2)) in TLH lambs were lower, whereas
      interalveolar wall thickness (83.0 +/- 3.1 microm) was greater than in control
      lambs (2,263.6 +/- 261.6 x 10(6), 46.7 +/- 4.8 m(2), and 68.6 +/- 2.1 microm,
      respectively). Our data show that TO restores most aspects of lung structure to
      normal in fetuses with lung hypoplasia but leads to altered alveolar development.
      The presence of fewer, larger alveoli in postnatal TLH animals may predispose
      these animals to respiratory complications during later life.

PMID- 11568988
TI  - Acceleration of lung disease in children with cystic fibrosis after Pseudomonas
      aeruginosa acquisition.
AB  - As part of the ongoing Wisconsin Cystic Fibrosis (CF) Neonatal Screening Project,
      we had the unique opportunity to study the longitudinal relationship between
      Pseudomonas aeruginosa (Pa) acquisition and infection and developing lung disease
      in children with CF. The primary objective was to determine whether acquisition
      of Pa was associated with a measurable change in the progression of lung disease.
      Two outcome measures were used to study 56 patients who were diagnosed through
      newborn screening: 1) Wisconsin additive chest radiograph score (WCXR), based on
      the average of scores from a pulmonologist and a radiologist, and 2) the highest
      forced expired volume in 1 sec (FEV(1))/forced vital capacity (FVC) ratio. We
      used two measures of Pa acquisition: 1) time of first positive protocol
      determined oropharyngeal (with cough) culture, and 2) the magnitude of antibody
      titer detected by ELISA assays, using as antigen a crude cell lysate, purified
      exotoxin A, or an elastase toxoid prepared from three Pa strains. Other predictor
      variables included age, pancreatic status, height-for age, and weight-for-age
      percentiles. The best regression model for predicting changes in the WCXR
      included time to first positive culture and antibody titer for Pa elastase. Prior
      to Pa acquisition, WCXR worsened by 0.45 points/year (P > 0.25); after Pa
      acquisition, the rate of worsening increased significantly (P < 0.001) to 1.40
      points/year. Each antibody titer level (log base 2) increased the score by 0.48
      points (P < 0.001). The best regression model for predicting change in the
      FEV(1)/FVC included only time to first positive culture. Prior to Pa acquisition,
      the FEV(1)/FVC ratio declined by 1.29%/year; after Pa infection, the rate of
      decrease significantly accelerated to 1.81%/year (P = 0.001). Our data show that
      Pa acquisition is associated with declining pulmonary status in children with CF,
      and that this effect is probably gradual rather than precipitous. Because these
      patients were diagnosed and treated aggressively, our estimates of the effects of
      Pa acquisition may be conservative. We also conclude that the WCXR appears to be
      more sensitive than FEV(1)/FVC in detecting early changes in lung disease
      associated with CF.

PMID- 11568989
TI  - Genotypic characterization of Pseudomonas aeruginosa strains recovered from
      patients with cystic fibrosis after initial and subsequent colonization.
AB  - Chronic infection by Pseudomonas aeruginosa (PA) in patients with cystic fibrosis
      (CF) is preceded by a period of colonization and acute infection. Early
      aggressive antibiotic treatment of initial colonisation may prevent or at least
      delay chronic pulmonary infection. We initiated treatment with a combination of
      IV beta-lactam tobramycin, followed by nebulized colistin when PA was first
      isolated from patients with CF. Subsequent serial PA isolates obtained from these
      colonized CF patients were characterized by means of molecular methods to
      determine whether they were genetically related to the initial strain. Initial
      colonization was eradicated in all 19 patients. All patients reacquired PA within
      3-25 months during the 3 years of follow-up. Fourteen patients acquired a new PA
      strain with a distinct genotypic profile, suggesting a new source of
      contamination. Five patients had two PA isolates with identical genotypes,
      suggesting either previous undetected respiratory tract colonization or a
      persistent environmental source of contamination.

PMID- 11568990
TI  - Beclomethasone diproprionate reduced airway inflammation without adrenal
      suppression in young children with cystic fibrosis: a pilot study.
AB  - Inhaled corticosteroids are commonly used in cystic fibrosis (CF), but there are
      few studies evaluating their safety in young children. We, therefore,
      prospectively administered beclomethasone diproprionate (BDP) to 12 clinically
      stable young children with CF to examine the safety of this therapy with respect
      to adrenal suppression and airway infection. To determine potential mechanisms of
      corticosteroid action in CF, we also examined airway markers of inflammation
      before and after inhaled steroid treatment. BDP 210 microg twice a day was given
      via spacer for 2 months. Twelve-hour serum and urine cortisols and response to
      low-dose synthetic ACTH cortisol stimulation were assessed. Bronchoalveolar
      lavage fluid (BALF) was examined pre- and posttreatment with BDP by quantitative
      bacteriology and indices of airway inflammation, including levels of total
      neutrophils, neutrophil elastase-alpha-1 antiprotease complexes (NEAP), CA 19-9
      mucin-associated antigen, interleukin-8 (IL-8), and macrophage IL-8 mRNA.
      Following 2 months of treatment, serum and urine cortisol levels were unchanged.
      Response to low-dose ACTH cortisol stimulation was not significantly decreased at
      30 min. Posttreatment BALF bacterial density was not statistically different from
      pretreatment; however, one patient who was initially culture negative became
      culture-positive with Hemophilus influenzae. BALF total neutrophil counts,
      corrected for epithelial lining fluid dilution, were decreased to approximately
      one third of pretreatment values (P = 0.03). NEAP and CA 19-9 mucin-associated
      antigen demonstrated similar decreases. BALF IL-8 levels and macrophage IL-8 mRNA
      levels were not statistically changed. These findings suggest that treatment with
      BDP 420 microg per day for 2 months in young children with CF does not affect
      urine and blood cortisol, causes no decrease in adrenal reserve, and does not
      result in a clinically significant increase in airway infection. In addition, the
      fall in bronchoalveolar lavage fluid inflammatory markers following BDP suggests
      possible modulation of neutrophil influx into the CF airway and provides
      justification for further studies of inhaled corticosteroids in CF.

PMID- 11568991
TI  - Chronic lung disease of the newborn is not associated with Ureaplasma
      urealyticum.
AB  - To clarify the association of Ureaplasma urealyticum infection with chronic lung
      disease of the newborn 145 preterm infants less than 34 weeks of gestation were
      examined. The infants were enrolled during two separate periods. The presence of
      U. urealyticum was studied by obtaining endotracheal culture samples and blood
      samples; if either of these samples grew the organism, the child was regarded as
      having U. urealyticum infection. Infection with U. urealyticum was detected in
      33%, and chronic lung disease (defined as the need for oxygen, and typical chest
      radiograph at 28 days of age) in 43% of infants. The development of chronic lung
      disease was not associated with the presence of U. urealyticum. Our results
      suggest only a minor indirect role for U. urealyticum in the development of
      chronic lung disease of the newborn.

PMID- 11568992
TI  - Exhaled nitric oxide and asthma in young children.
AB  - Exhaled nitric oxide (eNO) has been used to diagnose asthma in adults and
      children using either the slow vital capacity method (SVCm) or, in younger
      children, the tidal breathing method (TBm). Adenosine 5'-monophosphate (AMP)
      challenge also has been found to be a sensitive and specific test for the
      diagnosis of asthma. In the present study, we used the AMP provocation
      concentration that caused wheezing (PCW) to confirm the diagnosis of asthma (PCW
      < or = 200 mg/mL). We studied 36 children (2-7 years) with mild intermittent
      asthma, 13 children (3-7 years) with moderate persistent asthma treated with
      inhaled steroids, 20 nonasthmatic children (2-7 years) with chronic cough and
      recurrent pneumonia, and 15 healthy children (4-6 years). Expired gas was
      collected in collection bags by the TBm, and eNO was measured. We evaluated the
      efficacy of eNO values in diagnosing asthma. The mean eNO level of the mild
      intermittent asthmatic children (5.6 +/- 0.4 ppb) not receiving inhaled
      corticosteroids was significantly higher (ANOVA P < 0.0001) than that of the
      moderate persistent asthmatics who were treated with inhaled steroids, the
      nonasthmatic children with chronic cough, and the group of healthy children (3.7
      +/- 0.6 ppb, P < 0.05; 3.2 +/- 0.3 ppb, P < 0.001; 2.2 +/- 0.2 ppb, P < 0.001,
      respectively). The points of intersection for sensitivity and specificity curves
      of eNO to differentiate mild intermittent asthmatics from nonasthmatic children
      with chronic cough and from healthy children were 77% and 88% for eNO values of
      3.8 ppb and 2.9 ppb, respectively. We conclude that eNO collected by the TBm can
      differentiate steroid-naive young children with intermittent asthma from healthy
      children, from nonasthmatic children with chronic cough, and from asthmatic
      children treated with inhaled steroids.

PMID- 11568993
TI  - Efficacy and safety of aerosolized tobramycin in cystic fibrosis.
AB  - Aerosolized tobramycin has been extensively used in cystic fibrosis (CF) patients
      in order to directly deliver the antibiotic to the endobronchial site of
      infection, and decrease toxicity by limiting systemic absorption. Aerosolized
      tobramycin doses ranging from 80 mg twice or three times daily to 600 mg three
      times daily have been used in various clinical trials. At an 80-mg dose,
      preservation of pulmonary function with little or no improvement over the
      baseline was reported. Tobramycin, nebulized at 600 mg three times daily,
      significantly improved clinical and pulmonary functions and reduced the density
      of Pseudomonas aeruginosa in the sputum. No ototoxicity or nephrotoxicity was
      reported at either dose. TOBI, a tobramycin solution for inhalation, received
      Food and Drug Administration approval for maintenance treatment of P. aeruginosa
      lung infections in CF patients at least 6 years of age. Patients received TOBI
      nebulize 300 mg of tobramycin every 12 hr daily for 28 days, followed by 28 days
      off the drug in alternating cycles. In phase III trials, TOBI improved pulmonary
      function and decreased sputum density of P. aeruginosa compared to placebo. Serum
      creatinine was minimally, transiently elevated in both groups. More patients in
      the TOBI group reported voice alterations. All reports of tinnitus were in the
      TOBI group. An increased risk of emergence of resistant strains of P. aeruginosa
      was noted at all doses, after prolonged use.

PMID- 11568994
TI  - Congenital lung disease: a plea for clear thinking and clear nomenclature.
AB  - Antenatal ultrasound has allowed the discovery of abnormalities which in the past
      often escaped detection. It may be unclear what advice to offer. Many large lung
      malformations seen at the routine 20-weeks gestation scan have largely
      disappeared at term. There is now even more confusion in terms of how these
      malformations should be described. The nomenclature of congenital lung disease
      was never very clear, with terms such as sequestrated segment, cystic adenomatoid
      malformation, hypoplastic lung, and malinosculation being used to describe often
      overlapping abnormalities. However, today these terms are used inconsistently in
      the ante- and postnatal periods. For example, congenital cystic adenomatoid
      malformation (CCAM) is used prenatally to describe a lesion which may well
      disappear before birth, but is used postnatally to describe an abnormality which
      may require lobectomy. CCAM may have a pulmonary arterial supply, or be supplied
      like a sequestration from the aorta, and histological features of both lesions
      may coexist. Thus, a complete reappraisal of the nomenclature of congenital lung
      disease is timely; this review does not discuss treatment options.

PMID- 11568995
TI  - Survival following Burkholderia cepacia sepsis in a patient with cystic fibrosis
      treated with corticosteroids.
AB  - We describe an 11-year-old girl with cystic fibrosis (CF) who presented with
      respiratory failure and Burkholderia cepacia bacteremia (cepacia syndrome). She
      survived her illness after aggressive treatment with parenteral antibiotics and
      corticosteroids. We speculate that treatment with corticosteroids may decrease
      the influx of proinflammatory cytokines and neutrophil-induced inflammation, with
      resulting improvement in the outcome of cepacia syndrome in CF patients.

PMID- 11568996
TI  - Femoral shaft fractures during childhood.
AB  - The treatment of femoral shaft fractures in the child is influenced by the
      anatomophysiological peculiarities of the bone in childhood. The authors report a
      personal series of 51 fractures treated surgically (Kuntschner, Rush, Kirshner,
      external fixator), and they analyze the most significant aspects of fractures of
      the diaphyseal segments during childhood: post-fracture lengthening and the
      ability for post-fracture malalignment to self-correct. Also considered are the
      different methods of treatment, emphasizing advantages and disadvantages (from an
      economical point of view, as well), to emphasize the authors' therapeutic
      orientation. Under 6-7 years: trans-skeletal traction for 5-6 days, reduction in
      narcosis without expecting to achieve anatomical reduction, pelvipodalic plaster.
      Over 10 years: surgical indications are more frequent, until they are the same as
      those for adults aged over 13-14 years. Between 7 and 10 years of age is a no
      man's land, where indications for surgery must be made based on the individual
      surgeon's experience.

PMID- 11568997
TI  - Intra- and extra-pelvic lesions associated with unstable fractures of the pelvic
      ring.
AB  - Fracture of the pelvis is often caused by high-energy trauma, and for this reason
      it is frequently associated with fractures in other regions, hemorrhages, or
      severe lesions of the organs. Based on an analysis of the results, obtained by a
      review of 68 cases of unstable fracture of the pelvis treated at the IIIrd
      Division of the Rizzoli Orthopaedic Institute between 1980 and 1995, the authors
      make several suggestions concerning diagnosis and therapy for the evaluation and
      treatment of these patients.

PMID- 11568998
TI  - Ceramic-ceramic in total hip arthroplasty. An analysis of 7-13 year survival
      rate.
AB  - After 7-13 years, the long-term results of primary replacement of the hip joint
      by total cemented arthroplasty, with a head and acetabulum in high-density
      alumina, and a stem in chrome-cobalt alloy in a series of 38 patients were
      analyzed. The age of the patients ranged from 36 to 76 years (mean 55 years). The
      patients were monitored annually, by both clinical-radiographic follow-up and by
      an interview over the telephone (pain, independence walking, degree of hip
      flexion). The presence of a correlation between loosening of the implant and
      several clinical parameters (age, sex, diagnosis) and radiographic parameters
      (orientation, height and lateralization of the acetabular cup, rotation center of
      the implant, position of the femoral stem) were searched for. Data concerning 35
      of the 43 prostheses implanted were gathered. The data were analyzed by the
      survival curve with an actuarial method, log-rank test and chi square test. The
      differences were considered significant for p < 0.05. There were no clinical or
      radiographic signs of loosening of the femoral prosthetic component. Instead, the
      acetabular cup was loosened in 7 cases. An implant was removed because of
      infective complications 6 months after surgery. The cumulative percentage of
      survival of the implant after 13 years was 81.2%. There was no statistically
      significant correlation between loosening of the implant and the parameters
      considered. Despite the favorable mechanical features of bioceramics, the
      acetabular component proved to be the weak point of the implant. The authors
      believe that only the introduction of new concepts of acetabular fixation could
      contribute to a significant increase in the survival rate for ceramic-ceramic.

PMID- 11568999
TI  - Snapping hip: etiopathogenesis and surgical treatment.
AB  - Snapping hip is a polymorphous pathology the genesis of which is multifactorial,
      characterized by a snapping sensation which may be painful, and occurring during
      movement of the hip or during walking. Clinical and instrumental diagnosis for an
      accurate etiopathogenetic classification is essential to correct surgical
      treatment, that must be reserved only for cases with painful symptoms and with
      disorders in walking. The authors provide a classification system of the
      syndrome, describing four different varieties of the pathology and relative
      surgical treatment.

PMID- 11569000
TI  - A new fork-shaped condylar and osteotomy plate.
AB  - The authors present their experience with a new crossed condylar and osteotomy
      plate, which is innovative because of the features of its design, and the
      instrumentation used for its application, as compared to the traditional AO blade
      plate. The plate is called "fork-shaped" because there are 2 prongs in place of
      the blade with a "U" profile, and it involves the use of more accurate and less
      traumatic instrumentation to implant it. The results of a study conducted on a
      group of 20 patients, who were homogeneous for pathology and surgery, treated by
      a fork-shaped osteotomy plate, compared with an equal number of patients treated
      by a blade plate, are reported. The results were better in the group treated with
      a fork plate because there was a more accurate correspondence with the
      preoperative planning, and because there were fewer intraoperative complications,
      and time required for surgery was shorter.

PMID- 11569001
TI  - Intra-articular deformities of the knee in congenital hypoplasias of the lower
      limb: an arthroscopic study.
AB  - A knowledge of the morphology of the cruciate ligaments in congenital hypoplasias
      of the lower limb, susceptible to treatment to even the length discrepancy, is of
      practical importance in the prevention of subdislocation and dislocation of the
      knee during the distraction phase of femoral and/or tibial lengthening. The
      authors report their experience with 20 arthroscopies diagnosed in 20 children
      affected with congenital hypoplasia of the lower limb (shoft congenital femur,
      longitudinal peroneal hemimelia) performed prior to assembling the Ilizarov
      external fixator for femoral and/or tibial lengthening. None of the patients had
      congenital dislocation of the knee or knee with recurvation. In the patients in
      our study, it is possible to demonstrate that the anatomical cause of instability
      of the knee in congenital hypoplasias of the lower limb may be constituted by
      aplasia of one or both cruciate ligaments.

PMID- 11569002
TI  - Prospects and advantages in the use of cartilage cell cultures for in vivo
      transplants.
AB  - The authors present a critical analysis of the literature in order to evaluate
      the current prospects and advantages of cartilage cell cultures for in vivo
      transplants. The analysis is relative to their use or to the treatment of
      isolated osteochondral lesions of the knee, and it is preceded by an analysis of
      the methods used in the treatment of this pathology, such as: 1) debridement, 2)
      abrasion of the subchondral bone, 3) perforations and decortication of the
      subchondral bone, 4) perichondral transplants. The most significant results
      obtained for cartilage cell transplants for the repair of focal osteochondral
      defects in experiments conducted on animals and in successive clinical trials in
      man, also revealing the complex problems that may lead to a variability in
      chondrocytary activity, going from an in vitro to an in vivo environment, are
      presented.

PMID- 11569003
TI  - Rehabitation of allograft with bone dehydrated with solvents in reconstruction
      after removal of bone tumors: MRI evaluation.
AB  - It was the purpose of this study to analyze the behavior of Tutoplast bone
      allograf to fill cavities produced by the removal of benigning bone tumors of
      those with local malignancy. X-ray and MR images obtained during follow-up
      demonstrated an increase in the signal in all of the sequences within the graft,
      indicating complete rehabitation of the grafted area.

PMID- 11569004
TI  - The history of the diagnosis and treatment of lumbar sciatic disc herniation.

PMID- 11569006
TI  - Autosomal dominant transmission of bilateral "opposable" triphalangeal thumb.
AB  - Triphalangeal thumb occurs in two functional types: opposable and non-opposable.
      The opposable type presents a rudimentary middle phalanx and the thumb is
      frequently angulated. The non-opposable type presents a finger-like thumb (five
      fingered hand). Triphalangeal thumb often occurs in syndromes where other
      anomalies are present, so its pattern of inheritance has often been described
      jointly with the syndrome itself, then conflicting patterns of inheritance have
      been reported in literature. The present study reports upon the character of
      "bilateral opposable triphalangeal thumb" occurring isolated, without association
      of other anomalies. Authors studied the phenotype distribution in a family over
      five generations. They found that this character is transmitted with an autosomal
      dominant pattern of inheritance, and affected individuals are heterozygotes.

PMID- 11569005
TI  - An atypical presentation of Paget's disease in an immunocompromised individual. A
      case report.
AB  - Paget's disease of bone is a localized disorder of bony resorption. The mechanism
      underlying the development of the disease remains controversial. There is
      substantial evidence suggesting a genetic basis for Paget's disease in some
      patients. A viral etiology of Paget's disease has been advocated. A further
      hypothesis implicating an immunological mechanism for this disease is based on
      growing evidence reviewed in the text. The presented case showed clinical and X
      ray features typical of a very aggressive form of Paget's disease. We hypothesize
      that the extreme local aggressiveness of this case was secondary to the patient's
      concomitant immunosuppression due to an extended therapy following renal
      transplant.

PMID- 11569007
TI  - Arthropathy in factor VII coagulation deficiency. Description of a clinical case.

PMID- 11569008
TI  - The wrong approach to tumors of the musculo skeletal system: what should not be
      done.

PMID- 11569009
TI  - The supraepitrochlear process of the humerus.
AB  - On the basis of five cases of supraepitrochlear process of the humerus the
      authors recall the most significant anatomical and clinical aspects of the
      disease. The presence of clinical symptoms, going under the name of Struthers
      syndrome, indicates surgical removal.

PMID- 11569010
TI  - Traumatic avulsion of the brachial triceps tendon. Description of one case.
AB  - The authors describe a case of traumatic avulsion of the brachial triceps tendon,
      an exceptional lesion, that must be suspected when it is impossible to extend the
      elbow against resistance, with pain specifically at the olecranon insertion of
      the same. Surgical treatment consists in transosseous and periosteal reinsertion,
      guaranteeing excellent results if carried out within one week of trauma.

PMID- 11569011
TI  - Travel notes: the Spaulding Rehabilitation Hospital (SRH) in Boston (USA).

PMID- 11569012
TI  - Frequent complications in distal femoral osteotomy: a retrospective 8 year
      multicenter follow-up.
AB  - A total of 32 distal femoral osteotomies performed between 1971 and 1993 were
      evaluated, with a follow-up of 8 (2-23) years. Indications were lateral
      gonarthrosis in 23 cases (group I), and there were a variety of other indications
      in 9 cases (group 2). Twenty-six of the patients were submitted to revision
      surgery. Eleven operations were performed as a result of complications, such as
      pseudarthrosis (5), deep infection (3), and stiff knee (3). The remaining 16 were
      removals of fixation devices and they were not considered complications. Clinical
      results were evaluated based on different clinical scores (HSS, Lysholm, and
      Tegner) and NHP (Nottingham Health Profile), and there were 10 cases with good or
      excellent results. Results were better if the postoperative HKA angle (Hip-Knee
      Ankle) was within 0-8 degrees of varus. As accuracy of correction is of
      importance, and serious complications frequent, it is important to entrust cases
      such as these to the care of surgeons with a good knowledge of the surgical
      technique.

PMID- 11569013
TI  - Treatment of the sequelae of primary pathology of the hip by correction osteotomy
      and femoral lengthening using a combined external fixator.
AB  - It is not an exceptional event to observe the sequelae of primary pathology of
      the hip in young patients that, as such, are not of the ideal age for replacement
      surgery. Moreover, one must not overlook the difficulties involved in replacement
      surgery for the treatment of inveterate modifications in the normal hip anatomy.
      Often, among the sequelae of primary pathology of the hip, deformities of the
      lower limb must also be included, associated or consequent, which also need
      treatment. For these reasons, the authors, in three selected cases, used a
      combined external fixator (circular and lateral) by means of which they were at
      the same time able to correct the axial deformity (with a support osteotomy), and
      the residual hypometria (with femoral lengthening). Osteotomy plus lengthening,
      using an external fixator, avoid hypometria of the limb and deformity in valgus
      of the knee, and allow for results which would otherwise not be obtained with
      replacement surgery alone.

PMID- 11569014
TI  - Hip arthroplasty after femoral osteotomy.
AB  - The authors report the results of 56 prosthetic implants on previous femoral
      osteotomy. The cases submitted to surgery, some time after the operation, present
      with clinical-radiographic results (movement and risk of loosening) that are
      worse than those cases that had not undergone osteotomy. Among complications, a
      higher incidence of intraoperative fractures and nerve paralysis were observed.
      Fractures always occurred when instrumentation was removed during the same
      prosthetic implantation procedure.

PMID- 11569015
TI  - Hemiarthroplasty of the shoulder. Clinical experience in 18 cases treated by the
      Neer monoblock prosthesis.
AB  - The authors report the results of 18 hemiarthroplasties of the shoulder performed
      between 1990 and 1994 using the Neer II monoblock prosthesis, emphasizing the
      technical and surgical problems encountered. The patients treated numbered 13 for
      traumatic pathology (acute fractures: 7; sequelae of fracture of the proximal
      epiphysis of the humerus: 6), and 5 for degenerative lesions (arthrosis: 3;
      rheumatoid arthritis: 2). An evaluation of the results was based on the Constant
      method and isokinetic testing. Results based on follow-up obtained after 2 to 6
      years were satisfactory in 83% of the cases.

PMID- 11569016
TI  - The surgical treatment of inveterate hip dislocation in children affected with
      cerebral palsy: a preliminary report.
AB  - The incidence of hip dislocation in patients affected with cerebral palsy is
      directly correlated with the degree of neurologic deficit. Surgical treatment
      aimed at stabilization of the coxofemoral joint relieves pain and avoids the
      occurrence of changes in the static of the pelvis and vertebral column. The
      authors report their experience with procedures for the recovery of joint
      congruency (release of the adductors and psoas, surgical reduction of the
      dislocated epiphysis, femoral shortening associated with varus-derotation at the
      osteotomy level, acetabuloplasty) performed in one or more surgical stages, and
      operations with a purely anthalgic purpose (innominate osteotomy according to
      Chiari), specifying relative indications in relation to age.

PMID- 11569017
TI  - Bizarre parosteal osteochondromatous proliferation (Nora's lesion). Description
      of six cases and a review of the literature.
AB  - The authors report their experience with 6 cases of bizarre parosteal
      osteochondromatous proliferation (BPOP) observed in 4 patients in its typical
      site (distal ends of the limbs), and in 2 patients where it was instead
      atypically localized in the humerus and femur. The histories of the patients
      revealed that 50% reported previous trauma in the site of lesion. Five patients
      were submitted to surgical exeresis, while the remaining patient refused to
      undergo any type of treatment because he was asymptomatic. At a mean follow-up of
      36 months 1 patient presented with recurrence (20%). BPOP is a rare
      pseudotumorous lesion with typical radiographic and histopathologic findings
      similar to to those of other benign and malignant tumor forms. A review of the
      small amount of literature in existence is used to analyze the elements that may
      lead to accurate differential diagnosis.

PMID- 11569018
TI  - Ilizarov external fixation in the treatment of comminuted leg fractures.
AB  - Fifty consecutive comminuted leg fractures were treated by Ilizarov external
      fixation. Eleven were closed fractures, 37 were Grade II, and 2 were Grade III
      open fractures. Forty-five fractures healed within 6 months. In 5 fractures the
      Ilizarov device was removed and healing occurred by intramedullary nailing (2
      cases) and decortication (3 cases). The causes of failure were: rapid peroneal
      union or bone fragment necrosis. Subjective tolerance and fracture stability are
      limited by septic loosening of the wires requiring frame removal after 6 to 8
      months. Excellent results may be obtained (no leg length discrepancy, no
      angulation, no rotation, no joint stiffness), but the time required for union is
      long and additional surgery is required.

PMID- 11569019
TI  - Traumatic dislocation of the knee. A review of the literature and our experience.
AB  - It is the purpose of this study to analyze the data found in the literature and
      to compare our experience with that of other traumatology centers. A series of
      patients observed between 1985 and 1996 were reviewed. Nine out of 12 patients
      with sequelae related to dislocation of the knee were re-evaluated. Based on an
      analysis of the results, obtained by using the International Knee Documentation
      Committee (IKDC) form, it was concluded that the patients treated surgically are
      better overall. It is possible only rarely to obtain satisfactory recovery in
      work and/or sports activity, as the lesion is severe and even when treated it
      leaves functional and/or structural sequelae of varying importance.

PMID- 11569020
TI  - Corrective osteotomy for the treatment of genu procurvatun. Surgery.
AB  - The authors present the method known as proximal tibial osteotomy for the
      treatment of genu procurvatum. The importance of an accurate preoperative study,
      particularly aimed at avoiding negative repercussions on the position of the
      patella, and of a correct anatomical exposure with isolation of the peroneal
      nerve for any iatrogenic lesions, must be emphasized; a condylic plate was used
      to stabilize osteotomy was stabilized, adapting well to the anatomy of the
      region, and allowing us to obtain correction of any associated deformities on the
      frontal plane.

PMID- 11569021
TI  - Pseudomalignant myositis ossificans in children. Description of a case and review
      of the literature.
AB  - The authors report a rare case of pseudomalignant myositis ossificans occurring
      during childhood. A female aged 10 years with no previous history of trauma came
      to their observation with findings of pain and progressive swelling in the
      gluteal region. The severity of the clinical findings and the absence of
      characteristic ossification in the x-rays obtained at the onset of the disease
      suggested that neoplastic pathology be excluded. Diagnosis (bone scan, CT scan,
      MRI, angiography, biopsy) and the progression of the disease, until its complete
      clinical resolution, are discussed in light of a review of the literature (44
      cases of pseudomalignant myositis ossificans during pediatric age). All of the
      elements that may be of help in diagnosis and capable of avoiding surgical
      procedures that are either untimely or improper are emphasized.

PMID- 11569022
TI  - Blount's disease.
AB  - Out of a total of 40 patients affected with Blount's disease treated at the
      Pediatric Orthopaedic Division of the Rizzoli Orthopaedic Institute between 1965
      and 1996, 29 were affected with the infantile type, and 11 with the adolescent
      type. In the group affected with infantile Blount's disease, the mean age was 5.5
      years, 11 were bilateral, for a total of 40 limbs affected, with a mean TMD angle
      of 24 degrees. All of the patients were treated by valgus osteotomy obtaining a
      percentage of poor results (insufficient correction or recurrence) equal to 25%
      according to Schoenecker's criteria. Mean follow-up was 3.6 years. In the group
      affected with adolescent Blount's disease, mean age was 12.6 years, the affection
      was always monolateral, the mean TMD angle was 15 degrees. All of the patients
      except 1 were treated by valgus osteotomy with elevation, and the results were
      constantly favorable. Mean follow-up was 2 years. The authors believe that the
      type of osteotomy used must be modulated based on the anatomopathologic findings
      of compromise in the proximal tibial metaepiphysis.

PMID- 11569023
TI  - Comparative morphofunctional investigation of vascular pool of the muscles of the
      elongated extremity using different distractional regimens.
AB  - Morphofunctional changes in intra-organ vessels of dogs' muscles were evaluated
      by rheovasography and stereometry methods of muscular preparations to reveal ATP
      ase, biochemical methods were used to determine tissue metabolism indices during
      elongation of tibia using different distractional regimens 1 mm 4 times per day
      (manual adjustment) and 1 mm 60 times per day (automatic distraction). The data
      obtained demonstrate different mechanisms for adequate intra-organ blood
      circulation in muscles using different distractional regimens.

PMID- 11569024
TI  - The surgical treatment of nonunion of the proximal metaphysis of the femur.
AB  - Nonunion of the proximal femur is a severe pathology, often provoked by the
      inopportune or improper use of a therapeutic aid: nonsurgical (primary nonunion),
      surgical (secondary nonunion). Surgical treatment of this nonunion may thus be
      characterized by different degrees of difficulty, depending on whether or not it
      is the sequela of surgery or of nonsurgical treatment. In lax nonunion, with
      atrophy of the segments and regions of necrotic bone interposed, modeling
      resection is required to correct the functional axes. The condylar blade-plate
      may be opposed by a cortical graft--to improve stability of the assembly-
      protecting the medial wall and providing the screws with excellent hold.

PMID- 11569025
TI  - Aseptic nonunion of the humeral shaft.
AB  - A total of 78 cases of aseptic nonunion of the humeral shaft treated at the third
      division of the Rizzoli Orthopaedic Institute between 1980 and 1997 were
      evaluated. There was a mean time of 19 months between trauma and definitive
      treatment. Surgical treatment consisted in osteosynthesis with a plate and bone
      grafting in 75 cases, and synthesis with screwed bone grafting alone in 3 cases.
      Consolidation was obtained in 96% of cases. The bone graft used (homo- or
      autoplastic) encountered complete osteointegration in a maximum time of 8 months.
      Postoperative motility of the shoulder and elbow were comparable to the
      preoperative findings.

PMID- 11569026
TI  - The Epibloc system for the treatment of wrist fractures.
AB  - The current prospective study was conducted to verify the results obtained in a
      heterogeneous group of 50 displaced fractures of the wrist treated with the
      Epibloc system. This method is simple and rapid to use and it does not require
      plaster. The results obtained are very satisfactory (good and excellent 91.6%) in
      AO type A2 and A3 fractures and in type C1 fractures (92.8%) and in C2 fractures
      (88.3%); in fractures with multiple fragments and compromise of the joint surface
      (C3) the results were not very significant because of the small number of lesions
      treated (4 cases), but they do not seem to differ very much from what was
      obtained by other authors when more complicated methods were used. The results
      were very unsatisfactory in type B fractures (Goyrand); it is our belief that
      this method is not indicated for lesions such as these, because of the intrinsic
      difficulty in monitoring dislocation of the volar metaepiphyseal fragment.

PMID- 11569027
TI  - An evaluation of the results of two non-surgical methods in the treatment of
      fractures of the odontoid process.
AB  - The authors illustrate the results of a series of 47 fractures of the odontoid
      process all treated according to two non-surgical methods, among the most
      diffused and accepted: Minerva plaster and halo-plaster. The various elements
      used to classify odontoid fractures are examined, as is their importance for
      prognosis. The conclusions refer to two essential points: 1) fractures with a
      higher risk of nonunion are Anderson type II, with posterior shifting, in elderly
      patients; 2) reduction and immobilization with a halo-plaster may be considered
      the first choice of a method for most of these fractures, in consideration of the
      limited risk of nonunion involved.

PMID- 11569028
TI  - Superior thoracic outlet syndrome.
AB  - The authors discuss Superior Thoracic Outlet Syndrome (STOS), which is
      characterized by aspecific symptomatology. However, some tests may be used to
      reveal the specificity of the disease. In the past, treatment was often followed
      by recurrence of the disease. In the last ten years, the Roos operation has been
      used with a high success rate.

PMID- 11569029
TI  - Lateral epicondylitis: clinical classification and proposal for treatment.
AB  - The authors report their experience in a retrospective study on a sample year
      (1997) of cases (77 in number) of lateral epicondylitis treated non-surgically at
      the Rizzoli Orthopaedic Institute. The results for the 63 patients reviewed are
      very disappointing (healing only in 36.5% of cases). In their opinion, this may
      be attributed to the lack of an accurate clinical definition of the pathology,
      and an inadequate treatment protocol. They conclude with the proposal to classify
      3 clinical forms for epicondylitis (acute, chronic recurrent, and chronic
      persistent) and to follow a corresponding treatment protocol, aimed at improving
      results.

PMID- 11569030
TI  - Capsuloplasty for the treatment of recurrent anterior dislocation of the
      shoulder: long-term evaluations of the Putti-Platt method and Bankart method with
      anchors.
AB  - The authors compare two methods used for the treatment of recurrent anterior
      shoulder dislocations: Putti-Platt capsulomyoplasty, based on an overlapping
      suture of the free margins of the joint capsule and of the subscapularis muscle,
      and the Bankart method that uses anchors, based on the repair of the glenoid
      labrum, that is kept in site, together with the medial flap of the joint capsule,
      by suturing with the anchors previously stabilized to the neck of the glena. In
      this method, the subscapularis muscle is re-approximated without any overlapping
      or shortening. The Bankart method with anchors thus allows us to obtain
      anatomical repair of the lesion, with doubtless advantages for mobility, function
      and stability of the shoulder; this is confirmed by the comparison with results
      obtained out of 34 patients in this study, 15 of which submitted to the Putti
      Platt method, 19 to the Bankart method with anchors. The latter had reduction of
      external rotation which in none of the cases exceeded 25% (a reduction that at
      times achieved 50% in patients submitted to the Putti-Platt method (p = 0.001);
      difficulties in work or sports were minimum or absent (p = 0.003), recovery time
      was more rapid, without compromising joint stability (p = 0.069); these data
      allow us to consider the Bankart method with anchors the surgical method that is
      most indicated for the treatment of anterior glenohumeral instability.

PMID- 11569031
TI  - Supracondylar fracture of the femur following total knee arthroplasty.
      Description of two clinical cases.
AB  - The authors describe two cases of supracondylar fracture of the femur occurring
      following total knee arthroplasty. By reviewing the literature, they analyze
      causal factors indicating the constant presence, observed also in the cases
      presented, of an erroneous resection of the anterior cortex of the femur. In
      association with other predisposing factors, this condition favors an anomalous
      distribution of the load forces in this site, reducing torsion resistance of the
      femur by about 30%: what results is greater susceptibility for the risk of
      fracture for a long period of time, even for trauma of moderate entity.

PMID- 11569032
TI  - Parafocal osteotomy and the Ilizarov method in the treatment of femoral
      pseudarthrosis. Case report.
AB  - The case presented is that of a man aged 54 years, with hypertrophic
      pseudarthrosis shortening by 3 cm and a femoral mechanical axis measuring 13
      degrees varus. Parafocal osteotomy according to Paltrinieri was carried out with
      the aim of correcting the varus femur, the shortening and, secondarily, of
      obtaining recovery from the pseudarthrosis. Osteosynthesis was achieved by the
      Ilizarov apparatus. Axial correction and lengthening were obtained after 33 days.
      The fixator was removed after 5 months and 10 days, during which the nonunion
      appeared healed.

PMID- 11569033
TI  - Osteomyelitis of the pubic symphysis, abscess and late disjunction after
      delivery. A case report.
AB  - Infection of the pubic symphysis after delivery is rare, and probably occurs
      through a small vaginal laceration and is usually silent in the early phase: as
      the disease progresses, bone infection, sequestra formation and septicemia man
      occur. This report presents one case of staphylococcal osteomyelitis of the
      symphysis in a twenty five years old woman, with onset of symptoms 2 months after
      delivery. Staphylococcus Aureus was collected from pus and blood. Bone sequestra
      and a large abscess extending in the rectus abdominis fascia were present.
      Drainage and curettage resolved infection, but sourapubic pain persisted because
      of symphysis disjunction, and was treated by external pelvic fixation.

PMID- 11569034
TI  - Double lumbar fracture: a case study.

PMID- 11569035
TI  - The treatment of anterior recurrent dislocation of the shoulder: the Bankart
      Delitala procedure.
AB  - The authors report the results of 110 shoulder capsulorrhaphies performed
      according to the Bankart-Delitala technique. After a mean period of 104 months +/
      63 the clinical results, evaluated on the basis of the Rowe method were
      excellent-good in 94.6% of cases, and fair-poor in 5.4%. In 83.6% of cases there
      was no deficit in motility of the shoulder submitted to surgery, in 16.4%, the
      shoulder presented deficit in extrarotation (exceeding 15 degrees in only 1 case,
      equal to 0.9%).

PMID- 11569036
TI  - Subcutaneous rupture of the tendon of the long head of the biceps brachii in
      subacromial impingement syndrome.
AB  - Ruptures of the long head of the biceps brachii are mostly of degenerative
      nature, secondary to subacromial impingement and morphological changes in the
      bicipital groove. Clinical findings are typical. Treatment is controversial, as
      it may either be surgical or non-surgical. The authors considered only those
      cases in which tendinous rupture was the first manifestation of pathology caused
      by wearing, with typical deformity of the profile of the arm. The favorable
      results of surgical treatment in 14 patients aged from 38 to 70 years, followed
      up after an average of 10.9 years, are reported. Among surgical methods used,
      tenodesis at the bicipital groove currently constitutes the method of choice.

PMID- 11569037
TI  - Preliminary results in 167 bioceramic cemented arthroplasties with five-year
      follow-up in patients aged 60 years or over.
AB  - A total of 167 ceramic-ceramic cemented arthroplasties with a mean follow-up of
      62.5 months were evaluated. There were no signs of loosening in the femoral
      components. Loosening of the acetabulum was observed in 5 patients. A statistical
      study conducted on the two groups (the first aged under 70 years, the second aged
      70 or over) did not reveal any relationship between failure of the acetabular
      component and the age of the patient. An evaluation of bone density based on the
      DXA system in 5 cases of loosening revealed its diminution in relation to follow
      up parameters. Based on our experience, implantation of the ceramic-ceramic
      cemented prosthesis is a reliable choice in patients with good bone trophism, in
      those where there is a significant reduction in bone density; it is best to use
      polyethylene-ceramic implants.

PMID- 11569038
TI  - Vancomycin prophylaxis in joint arthroplasty.
AB  - Postoperative infections in prosthetic surgery still constitute a serious
      problem, and one that is difficult to treat, because of the occurrence of
      agglomerates of microbes that are resistant to immune defenses and antibiotics.
      In nearly all cases, removal of the prosthesis is the only possible means of
      solving the problem of infection. The systematic use of antibiotic prophylaxis in
      surgery of this sort offers advantages in terms of a reduction in the risk of
      infection. The authors present a personal case series relative to the strategies
      of perioperative antibiotic prophylaxis used in cases of hip and knee
      arthroplasty; we refer to 233 joint arthroplasties performed between October 1993
      and April 1996. In all of the cases, perioperative prophylaxis with vancomycin
      chlorohydrate at a dose of 1 g i.v. 1 hour prior to surgery, and 6-8 hours after
      surgery was carried out. The choice of the antibiotic was based on the
      epidemiological knowledge of the literature and the experience on the ward.

PMID- 11569039
TI  - Valgus-lateralization osteotomy: notes on surgery.
AB  - There are specific forms of nonunion secondary to per-inter-subtrochanteric
      fractures that make surgical planning a critical phase. In cases such as these,
      it may be useful to transform the center of the nonunion into an osteotomy plane.
      Because of the anatomotopographical features, course and progression of the
      lesion, cases such as these constitute a pathology that is difficult to define in
      terms of a therapeutic protocol. The authors report the surgical technique used
      in 4 cases of nonunion of the proximal metaphysis of the femur.

PMID- 11569040
TI  - The efficacy of arthroscopy in the treatment of hip osteoarthritis.
AB  - We evaluated the utility and the safety of arthroscopy for diagnosing and
      treating symptoms in patients with osteoarthritis (OA) of the hip. We studied 133
      patients consecutively treated for hip OA, using a modified Harris Hip Score
      (HHS) for the clinical assessment: There were no related complications or
      infections. At an average follow-up of 18 months, 61% of patients showed an
      improvement of their preoperative score, although only 36% of those actually
      presented good or excellent results. The remaining 39% of the total, either
      developed recurrent symptoms or underwent a major surgical procedure after
      arthroscopy. Benefit derived from the arthroscopy procedure depends strictly on
      either age or OA severity. Arthroscopy of the hip joint is a safe tool for
      managing problems related to OA of the hip. Careful selection of patients must be
      performed to identify those who will benefit most from the procedure. It seems
      that young patients with early OA are those associated with a higher rate of
      procedure success.

PMID- 11569041
TI  - Rigid fixation with plate and bone graft in failures of intramedullary
      osteosynthesis for the treatment of diaphyseal nonunion of the femur.
AB  - Fractures and diaphyseal nonunion of the femur are normally treated by
      intramedullary nailing. In cases in which nailing fails, nonunion is treated by
      reaming of the canal and substitution of the nail with one of a more adequate
      caliber. Rarely, however, due to unfavorable mechanical conditions or in cases of
      atrophic nonunion or with scarce vascularization the biological conditions for
      healing are absent. In cases such as these, nonunion must be treated by rigid
      internal fixation with a plate, aided by the use of cortical graft on the
      opposite side. The authors present 7 cases of diaphyseal nonunion of the femur
      treated between 1994 and 1996 using rigid fixation (plate and graft) as a salvage
      method, as a result of numerous previous failures in surgery. The results were
      favorable in all of the cases without complications.

PMID- 11569042
TI  - External dynamic fixation in fractures of the humerus: can it still be considered
      treatment of second choice?
AB  - The authors report 40 patients affected with diaphyseal fracture of the humerus
      treated by dynamic axial fixator (FAD Orthofix). Minimum follow-up was 2 years. A
      clinical and radiographic retrospective study was conducted with the purpose of
      verifying the validity of external fixation as treatment of choice in diaphyseal
      fractures of the humerus. The results were evaluated considering healing time,
      extent and type of complications, long-term clinical, radiographic and functional
      findings. Results were: excellent: 35; good: 2; fair: 2; poor: 1. Complications
      were: nonunione: 1; reimplantation of FAD screws: 1; 4 infections of the screw
      holes, 3 realignments due to secondary displacement, 1 re-fracture after removal
      of the implant. There were no iatrogenic lesions of the radial nerve, or
      infections of the fracture site. The authors conclude that this semi-invasive,
      versatile and well-tolerated method, may be considered a valid alternative to
      conservative treatment, or to internal fixation even in cases of single trauma,
      despite limits related to the degree of collaboration of the patient,
      particularly with regard to debridement of the screw holes and periodical
      clinical and radiographic monitoring.

PMID- 11569043
TI  - Fracture of the patella in children and adolescents.
AB  - Fractures of the patella in childhood and adolescence are a rare occurrence, and
      they are differentiated from those occurring the adult. Between 1975 and 1995, 76
      cases of fracture of the patella in patients aged under 15 years were treated at
      our institute. A mean clinical-radiographic follow-up of 2 years was available
      for all of the patients; 18 patients were followed-up after a considerable amount
      of time (mean 18 years). After analyzing the specific features that distinguish
      there fractures when they affect a subject who is still growing, the authors
      report the results obtained and the short and long-term complications observed.

PMID- 11569044
TI  - Quiz. Ependymoma.

PMID- 11569045
TI  - Quiz. Histopathological diagnosis was exostosis with nonunion secondary to
      probable fracture.

PMID- 11569046
TI  - Quiz. Tubercular osteoarthritis.

PMID- 11569047
TI  - Neurologic evaluation in thoracolumbar vertebral fractures.
AB  - A standardized and universal neurologic evaluation is of essential importance in
      defining the prognosis, treatment, and long-term results in patients with spinal
      cord injury. The American Spinal Injury Association was the first to publish a
      neurologic classification in 1992. This classification, which was subsequently
      submitted to numerous revisions, was also adopted by the International Medical
      Society of Paraplegia and by the national scientific associations of many other
      countries. In Italy, too, the ASIA/IMSOP form has been accepted as a standard for
      neurologic evaluation, but with the exception of specialized centers, it is still
      not well-known. The authors critically analyze the international terminology and
      its translation, they define the technical aspects of the neurologic examination
      in relation to priorities, and to the specific goals. Finally, they report
      several thoughts deriving from clinical practice in the Spinal Unit of Florence.

PMID- 11569048
TI  - Vertebral instability in non-neurologic thoracolumbar fractures: the predictive
      value of methods of measurement.
AB  - It is the purpose of this study to evaluate the radiographic results of the
      conservative treatment of fractures of the thoracolumbar passage in relation to
      the initial and long-term injury parameters measured by using three different
      methods: the sagittal index (SI), by Farcy et al., the McRae Index, the Knight et
      al. Index. The predictive value for each single method was calculated, to
      determine which of them could be reliable for the purposes of defining primary
      stability of the injured spine segment. The three methods of measurement were
      used for initial evaluation and at follow-up (mean 31 months; range 9-45) in 60
      non-neurologic thoracolumbar fractures treated conservatively. The fractures were
      classified based on Magerl et al. Initial instability was evaluated on the basis
      of the progression of the kyphotic deformity (by at least 5 Cobb degrees as
      compared to the pre-treatment condition). The Pearson chi 2 test was used for a
      statistical analysis of the data. There was progression in kyphosis of the
      fracture in 36 cases (60%). The sagittal index (SI) measured on initial X-rays
      revealed 27 (76%) potentially stable fractures, while the McRae Index considered
      19 to be at risk (55%), the Knight Index, 15 (43%). The higher predictive value
      (73%) of the sagittal index shows the greater reliability of this method of
      measurement, as compared to the McRae Index (predictive value = 60%) and the
      Knight Index (53%) in recognizing the initial phases to be those where the
      potential instability of the fracture is observed. Even when the SI is applied,
      the probability of an error in evaluation occurring is 27%. This fact once again
      stresses the need for more accurate radiological examinations (CT scan, MRI) that
      clarify the morphological aspects of the lesion injury in an exact manner.

PMID- 11569049
TI  - The results of the surgical and conservative treatment of non-neurologic
      comminuted thoracolumbar fractures.
AB  - A retrospective radiologic study of 40 non-neurologic thoracolumbar fractures
      allowed for the evaluation of the long-term results of surgical and conservative
      treatment in terms of correction of the post-traumatic deformity. The Magerl
      classification and the McCormack scale were used to select compressive type
      fractures (type A), and fractures characterized by comminution of the vertebral
      body without involvement of the posterior elements. Instability related to
      comminution and to considerable diastasis of the fragments is at the basis of
      failure of conservative (plaster brace) and surgical (short posterior fixation
      and posterolateral fusion) treatments. Severe type A fractures treated
      conservatively have, in fact, at follow-up shown significant residual deformity,
      while failure of the instrumentation or loss of correction in 40% of cases
      treated surgically has been revealed.

PMID- 11569050
TI  - The treatment of thoracic and lumbar spine fractures: a study of 123 cases
      treated surgically in 101 patients.
AB  - For a total of 123 thoracolumbar traumatic lesions treated surgically in 101
      patients over approximately 2 years (all monitored clinically and
      radiographically up to consolidation by follow-ups after from 6 to 26 months,
      mean 10 months) the technique used, complications and treatment are reported. The
      treatment procedure included: emergency surgery decompression, osteosynthesis,
      and fusion (posterior and possibly intersomatic); immediate recovery of function
      and loading; clinical and radiographic monitoring within 4-6 weeks, and possible
      anterior fusion in case of insufficient reconstruction of the anterior column.
      The complications observed out of 123 fractures were: collapse of the implant (4
      cases), infection (5 cases), liquoral fistula (1 case), transitory paralysis of
      the abdominal muscles homolateral to the lombotomic incision (1 case), TVP (2
      cases), bronchial pneumonia (2 cases), paralytic ileum (1 case). There was no
      sagittal deformity (secondary kyphosis) except for 5 cases of mechanical collapse
      that were resolved with a new operation. Neurologic deficit was caused by
      fracture in 49 patients (40% of the fractures or 48% of the patients). Six
      patients out of 30 affected with spinal cord lesion (20%) and 15 out of 19
      affected with cone and/or cauda lesion (79%) improved. There was no progression
      of the neurologic findings after surgery. The authors conclude by proposing a
      protocol of posterior osteosynthesis for the use of a system in titanium made up
      of pedicle screws and hooks connected to a pair of cylindrical bars joined
      together.

PMID- 11569051
TI  - The surgical treatment of thoracic and lumbar fractures by posterior approach.
AB  - A review of large case series, biomechanical studies and the development of
      surgical approaches and various types of instrumentation have led to different
      orientations in the surgical treatment of vertebral fractures. The authors
      present their experience in 67 cases treated by posterior approach using
      segmental fixation for the instability of the lesion and the possible association
      of neurologic deficit (Magerl A in 35 cases, B in 25, C in 7; Frankel A in 21
      cases, B in 15, C in 9, D in 6). At a mean follow-up of 3 years, treatment by
      posterior approach allowed us to suitably treat most of the vertebral fractures
      observed with clinically satisfactory results, but without observing a definite
      correlation between neurologic recovery and quality of the reduction. The overall
      realignment of the spine with extension synthesis and adequate geometry and the
      development of good bone callus allowed us to obtained a stable spine, protecting
      consolidation of the fractured metamere.

PMID- 11569052
TI  - Our experience in 33 cases of thoracolumbar fracture treated by transpedicle
      instrument.
AB  - Unstable thoracolumbar fracture (vertebromedullary traumatic lesion) is often the
      cause of poor sequelae, in lumbar pain caused by changes in the physiological
      sagittal profile, and sequelae of a neurologic nature. Thus, the concept of
      instability is further defined. The authors presents 33 cases of burst type
      thoracolumbar fractures treated by transpedicle instrumentation using the
      following systems: Malaga vertebral fixator 1,2 (MVF), Omega 21. Follow-up was
      obtained after rom 1 to 9 years. Results were: clinical-radiographic criteria (1.
      fusion, 2. deformity, 3. pain, 4. neurologic function). There was remodeling of
      the spinal cord canal in cases operated on. The authors conclude that a correct
      evaluation of instability of burst fractures and the consequent treatment of
      choice (transpedicle fixation) allows for a high favorable index of the
      functional capacity in these patients.

PMID- 11569053
TI  - Internal A-O fixator for the reduction and stabilization of thoracolumbar
      fractures.
AB  - The author report his experience in the surgical treatment of thoracolumbar
      fractures by posterior approach, using the A-O internal fixator (ISSF by Dick).
      The simplicity of the method, the effective biomechanical premises and the good
      clinical and radiological results, confirm, as reported by other authors with
      numerous cases, that the AO internal fixator constitutes an effective system for
      the reduction and stabilization of thoracolumbar fractures by posterior approach.

PMID- 11569054
TI  - USS internal fixator in lumbar and thoracolumbar vertebral fractures.
AB  - The authors report their experience in the surgical treatment of lumbar and
      thoracolumbar vertebral fractures with the use of the USS-AO internal fixator at
      the Division of Orthopaedics of the Azienda Ospedaliera OO.RR. in Foggia between
      July 1996 and July 1998. The cases, although not numerous, confirm the
      effectiveness of the method of correction and its maintenance even in time.

PMID- 11569055
TI  - Rehabilitation while standing.
AB  - Paraplegia caused by traumatic vertebrospinal lesions too often signifies
      paralyzing motor injury, and the rehabilitator is attributed the task of
      activating all of the rehabilitation procedures aimed at restoring an acceptable
      level of independence for the patient in terms of self-management and
      transferral. Traditional rehabilitation protocols have as a maximum objective the
      strengthening of the districts located above the injury, and their use in motori
      compensation operations aimed at maintaining the paralyzed region located below
      the injury. The main aim is that of training the patient to use the wheelchair
      and to adapt to his or her disability. Still today, many famous foreign spinal
      centers substitute the term "rehabilitation center" with "adaptation center."
      Today, we wish to bring the patient back to an erect physiological posture and
      walking, aided by his or her own limbs. New proposals for rehabilitation are
      observed that may be defined "rehabilitation while standing."

PMID- 11569056
TI  - Neuro-urologic disorders in the patient with spinal cord injury after vertebral
      fracture: progress in the uro-rehabilitative approach between diagnosis and
      treatment.
AB  - The treatment of urinary disorders in post-traumatic myelic pathology must
      necessarily include the physiatrist involved in the rehabilitation of the patient
      with spinal cord injury. The approach to the disability consequent to a spinal
      cord injury, in fact, cannot be separated from the rehabilitative treatment of
      bladder-sphincter deficit that always accompanies the clinical course of this
      pathology: neurourologic disorders always negatively influence the quality of the
      person's life, they are the cause of severe complications, and, at times, they
      are resistant to any combined medical-surgical-rehabilitative treatment.

PMID- 11569057
TI  - Early self-rehabilitation in thoracolumbar fractures (a guide for patients).
AB  - The authors report the purposes and the contents of a guide entitled "Early self
      rehabilitation in thoracolumbar fractures" currently used at the Division of
      Orthopaedics and Traumatology in the Macerata hospital, for patients affected
      with somatic "benign" fractures of the thoracolumbar passage (from T10 to L3).
      With elementary language and the support of simple images, several indications
      are given as to the anatomy and function of the column and its features, and the
      type of treatment used for fractures, so that the patient is aware of his or her
      lesion; the guide then becomes an actual manual for early and independent
      functional rehabilitation, capable of improving the physical and psychological
      state of the patient, in addition to favoring and accelerating healing. According
      to the authors, this study is useful in perfecting the relationship between
      physician and patient in the field of injuries of the vertebral column, which is
      often characterized by confusion and fear.

PMID- 11569058
TI  - Universal spine fracture classification.
AB  - A prospective, multi-center study was done to establish and evaluate a system for
      classifying spine fractures. The classification was designed with three goals in
      mind: 1) that the classification be easy to use and understand, 2) that the
      classification allow physicians, regardless of specialty, to communicate about
      spine fracture, 3) and to provide spine surgeons with a standardized tool to
      track treatment methods vs. outcomes. The classification uses five criteria to
      classify an injury: 1) columns injured, 2) extent of translatory displacement, 3)
      extent of angulation, 4) canal compromise, and 5) percent loss of height. Using
      these five criteria, fractures are classified into categories A, B, or C. After
      five years of field testing, statistical analysis, and refining, the
      classification system has proven to be useful and to provide consistent, reliable
      classification of spine fractures.

PMID- 11569059
TI  - Gleanings about dentistry from the world of literature. (Twenty-third in a
      series).

PMID- 11569060
TI  - Adalbert J. Volck (1828-1912): Confederate dentist, artist and anti-Lincoln
      satirist.
AB  - Dr. Adalbert Volck, a native of Bavaria, Germany, was a man of many talents: he
      was a skilled, innovative and versatile dentist, artist, artisan, craftsman, and
      a Confederate Civil War cartoonist and caricaturist. In 1848, after participating
      in a national revolution gone sour, Volck emigrated to the U.S. In 1852, Volck
      received his DDS degree from the Baltimore College of Dental Surgery, and
      subsequently, he established a life-long residency and dental practice in
      Baltimore. Dr. Volck gave staunch support to the spirit and force of organized
      dentistry. Among his professional accomplishments was his work in the early
      development of dental porcelain restorations. Although he was a non-combatant in
      the U.S. Civil War, Volck demonstrated his loyalty to the Southern cause by
      becoming a blockade runner; smuggler of drugs and medical supplies; "safe house"
      operator for Confederate soldiers and agents; Rebel spy; and personal courier for
      Jefferson Davis (the President of the Confederacy). The popular anti-Confederacy
      political cartoons of the great Thomas Nast inspired Volck to execute similar
      lampoons against the Union. Early in the war, Volck, through his caricatures,
      attacked the person and policies of President Lincoln and his Northern leaders.
      By using irony, sarcasm and ridicule, Volck attempted to sway popular sentiment
      toward the South.

PMID- 11569061
TI  - Further reflections on the toothpick in history and literature.

PMID- 11569062
TI  - A brief history of dentistry in Anatolia during the Turkish period.
AB  - The beginning of dentistry as a field independent of medicine started in the 18th
      century. Before then, dentistry had been as a part of medicine and surgery. Over
      the centuries, the contributions of ancient civilizations to dentistry prepared a
      foundation for the future of the field. The purpose of this short article is to
      emphasize the contribution of the Turks, particularly of their long-standing
      civilization in Anatolia to the field of dentistry.

PMID- 11569063
TI  - Dental postcards no. xx.

PMID- 11569064
TI  - Thomas B. Welch, MD, DDS: journalist, innovator and grape juice king.
AB  - Dr. Thomas B. ("T.B.") Welch was not an ordinary man. An inventive, creative and
      deeply religious individual, he intermittently practiced three professions--the
      ministry, medicine and dentistry. In his role as a minister, he developed a
      pasteurized, unfermented grape juice to be used during the communion service. He
      believed that he was truly serving God by enabling parishioners to partake a non
      alcoholic "fruit of the vine." At that time, wine (the alcohol-containing "cup of
      devils") was traditionally used. Although T.B.'s efforts were in vain, those of
      his son, Charles ("C.E.") Welch were far more successful. C.E. had greater
      entrepreneurial talents than his father. By the time Charles died in 1926, he had
      made Welch's Grape Juice a familiar household product. As a distinguished New
      Jersey dentist. Dr. Tom made many contributions to his profession. He greatly
      improved the quality of dental amalgam and cement, and his dental products were
      so successful commercially, that he quit the practice of dentistry sooner than
      anticipated. Additionally, he created, edited and wrote Dental Items of Interest,
      a professional journal with the second largest circulation in the country. Later,
      he edited several other dental journals. Of his seven children, three sons and
      one daughter followed him into the dental profession. T.B. was also a gifted
      poet. Possessing a keen interest in the English language, he attempted to
      simplify spelling by using phonetics. However, this endeavor failed.

PMID- 11569065
TI  - 19th century dentistry advertising trade cards: no. 7.

PMID- 11569066
TI  - Women in dentistry.

PMID- 11569067
TI  - Dentistry on stamps.

PMID- 11569068
TI  - The "roots" of the ideal filling material.

PMID- 11569069
TI  - Scientific dentistry 100 years ago.

PMID- 11569070
TI  - The risk of fat embolism during cemented total hip replacement in the elderly
      patient.
AB  - The increase in intramedullary pressure in the femur is the most decisive
      pathogenic factor for the development of embolic phenomena during total hip
      replacement. The aim of this study was to assess the risk of embolism and its
      clinical relevance during surgery by means of transesophageal echocardiography,
      hemodynamic and hemogasanalytic monitoring. A total of 65 arthroplasties entered
      the clinical trial. Total hip arthroplasty was cemented conventionally. The right
      heart was monitored intraoperatively by an echocardiography probe positioned in
      the patient's esophagus. Hemodynamic and hemogasanalytic monitoring were
      performed. Severe embolism occurred in 91% of the cases during implantation of
      the femoral component. Emodynamic and respiratory parameters showed significant
      changes after major embolism. The timing suggests a nearly immediate cause-and
      effect relationship. Acute hypotension was observed in 62% of the cases. Mean
      pulmonary shunt values increment was 30.5%. Patients with intraoperative embolism
      who had pre-existing associated diseases showed more severe and persistent
      cardiopulmonary dysfunction than healthy patients. The surgeon's proclivity to
      deny the clinical relevance of fat and bone marrow during during total hip
      arthroplasty is directly related to his awareness of and attempt to avoid
      embolism. Patients at risk require more intensive monitoring to obtain detailed
      information about hemodynamic and oxymetric parameters.

PMID- 11569071
TI  - Total hip arthroplasty in octogenarians: our experience.
AB  - The progressive aging of the population, a phenomenon that is common to all
      Western societies, means an increase in the number of patients aged over 80 years
      requiring total hip replacement. It is the purpose of this study to report our
      experience in the use of total hip replacement for the treatment of patients aged
      over 80 years. The study is retrospective, and it was conducted on a group of 27
      patients, for a total of 33 hips. An analysis of the results led us to conclude
      that there are no differences in indications for total hip replacement in
      patients aged over 80 years as compared to younger subjects. Nonetheless, it is
      important to carefully evaluate the general conditions of these patients, prior
      to surgery, because failure may have dramatic consequences.

PMID- 11569072
TI  - Preventive cobalt therapy in heterotopic ossification consequent to prosthetic
      hip reimplantation.
AB  - Prosthetic hip reimplantation is considered to be a procedure at risk for the
      development of periprosthetic heterotopic ossification, which may be responsible
      for functional limitations of the hip operated on. Preventive treatment may be
      carried out with radiation or drug therapy. The authors report the results of 54
      cases submitted to prosthetic reimplantation and treated by cobalt therapy, as
      compared to the results of 76 reimplantations (control group) that did not
      undergo any kind of treatment: the occurrence of high grade ossification
      (exceeding Brooker grade III) was 2% in cases treated, as compared to 9% in those
      not treated. Males were more at risk for the development of ossification.

PMID- 11569073
TI  - Recurrent anterior shoulder dislocation: preliminary experience in 29 cases
      treated by the Neer method and Statak screws.
AB  - The authors describe the surgical method used and present the preliminary results
      obtained in 29 patients affected with recurrent anterior dislocation of the
      shoulder treated by Neer capsuloplasty and Statak screws. The long-term results
      were evaluated based on the Rowe system: the score was excellent in 18 cases,
      good in 2, fair in 4, and poor in 5. All of the patients resumed work activity,
      with no restrictions, within 4 months of the onset of functional rehabilitation.
      The use of Statak screws allows us to simplify surgery, while guaranteeing repair
      of the Bankart lesion, when present. The method reported permits correction of
      instability, without excessive reduction of joint movement.

PMID- 11569074
TI  - Neer capsular shift surgery in the treatment of recurrent antero-inferior
      shoulder dislocations.
AB  - A total of 47 patients affected with recurrent multidirectional shoulder
      dislocation with a prevalent anteroinferior component were submitted to Neer
      inferior capsular shift surgery. Bankart lesion, present in 24 patients, was
      repaired prior to performing capsuloligamentous surgery. The patients included in
      the study presented with generalized ligamentous hyperlaxity in 20 cases, while
      hyperlaxity was localized in the pathological shoulder in the remaining cases,
      presumably related to the high number of dislocations. The choice of performing
      Neer inferior capsular shift surgery was initially based on the data and the
      modern conceptions that emerged in the literature. Successively, the good results
      obtained encouraged us to follow the path taken, and we are currently encouraged
      to advise this surgical procedure for the category of patients mentioned above.

PMID- 11569075
TI  - A new kind of rehabilitation after Neer capsuloplasty: results.
AB  - The shoulder joint constitutes a sophisticated compromise between stability and
      movement: trauma such as dislocation and the surgery that follows to restore
      anatomical integrity, may cause a change in this balance, resulting in myofascial
      retraction, neuromotorial inhibition, and a deviation in motorial programming
      with the appearance of compensation. It is the purpose of this study to report
      the results obtained with a specific rehabilitation program in 18 patients
      submitted to Neer capsuloplasty to treat anterior shoulder instability. An
      objective and subjective study with pre-established stages, and a 12-month follow
      up was done, to evaluate the results obtained based on the Rowe scale.

PMID- 11569076
TI  - Osteoid osteoma: diagnostic problems in joint and periarticular localizations.
AB  - The diagnosis of osteoid osteoma is usually not difficult. In typical forms of
      the disease, with diaphyseal localization, the clinical course and radiographic
      findings are so typical that diagnosis may be considered certain even when there
      is no histological confirmation. In some localizations, nonetheless, such as in
      the cancellous or short bones, or when the lesion involves a joint, diagnosis may
      be difficult, uncertain and late. Between January 1991 and April 1997 a total of
      91 patients who had been diagnosed as having osteoid osteoma were submitted to
      computed tomography. Of these patients, there were 34 females, and 57 males, and
      age ranged from a minimum of 2 to a maximum of 69 years. Localizations are
      reported in Table I. For the purposes of our study, several cases with atypical
      features have been selected from these. We found it interesting to emphasize the
      importance of a correct diagnostic procedure with the purpose of accurately
      identifying the lesion.

PMID- 11569077
TI  - Bizarre parosteal osteochondromatous proliferation. Difficulty in diagnosis.
AB  - Nora's tumor, also known as bizarre paraosteal osteochondromatous proliferation,
      is an exophytic outgrowth from the cortical surface that consists of a mixture of
      bone, cartilage, and fibrous tissue. It is a benign lesion with atypical
      microscopic features and a tendency to recur. Nora reported 35 cases emerging
      from the bones of the hands and feet. The largest published series is of 65
      cases, with 17 lesions involving the long bones. With this exception, most
      authors report isolated cases. Age range from 8 to 74 years but most patients are
      between 20 and 35 years of age, and with the lesion affecting males and females
      in equal proportions. Usually the presenting symptoMs are due to bony mass, with
      a variable growth rate (months-years), and infrequent pain. In 15-20% of the
      cases there was trauma in the patient history: nevertheless, Fechner and Mills
      report no association with trauma. Radiography shows a calcified, rounded mass
      emerging directly from the surface of the bone. Isotope bone scans show intense
      tracer uptake in the lesion. With time, the appearance progresses to the more
      characteristic mature bone architecture.

PMID- 11569078
TI  - Osteochondritis dissecans of the lateral femoral condyle.
AB  - Osteochondritis dissecans (OD) is a rare occurrence. In the knee, the most common
      localization is the lateral region of the internal femoral condyle. Involvement
      of the external condyle only occurs in 15% of cases, but its features are such
      that the situation is an entity in itself. The lesion is generally localized in
      the posterior site, and it is more extensive and more symptomatic as compared to
      medial localizations; moreover, early and rapid arthritic progression is
      observed. Reported here are 2 cases of OD of the lateral femoral condyle with
      atypical features in terms of clinical findings and progression of the disease as
      compared to more frequently occurring medial localizations.

PMID- 11569079
TI  - Post-traumatic reflex sympathetic dystrophy in the ankle and foot: a study of 32
      cases.
AB  - The etiopathogenesis of reflex sympathetic dystrophy is still undefined, and
      diagnosis and treatment are difficult. It is the purpose of this study to propose
      precise diagnostic and therapeutic criteria for post-traumatic reflex sympathetic
      dystrophy of the ankle and foot. Diagnosis is pre-eminently clinical. Clinical
      progression of the disease occurs in three stages: acute, dystrophic, chronic.
      Radiographic examination cannot be used to classify the stage of the syndrome.
      Bone scan with Tc 99M methylendiphosphonate aids diagnosis, and helps establish
      the prognosis of the disease. Clinical symptoms and instrumental tests (x-ray,
      bone scan, CT scan, MRI) are discussed in relation to differential diagnosis with
      other pathologies of the ankle and foot. Furthermore, the effective use of drugs,
      physiokinesitherapy, and hyperbaric oxygen therapy is discussed. The authors
      present a study of 32 patients, paying close attention to early clinical signs of
      the disease. X-ray examination and bone scan were routinely carried out in
      established diagnostic protocols.

PMID- 11569080
TI  - Hemorrhagic synovial lumbar cyst: a case report and review of the literature.
AB  - The authors report a case of an 81-year-old woman affected by a synovial cyst
      arising from the left facet joint of L3. The patient presented with severe pain
      and claudicatio spinalis. Diagnosis was based upon standard x-rays and MRI; the
      patient was operated on and the histology of the lesion confirmed the pre
      operative diagnosis. On MRI images the lesion appeared as a roundish extradural
      mass arising from the left facet joint of L3, compressing the cauda equina
      posteriorly, and it appeared with an increased heterogeneous signal, consistent
      with a high quantity of fluid and hemosiderin within the cyst. A communication
      between the lesion and the joint space was evident on the MRI sagittal
      reconstruction. Grossly the cut surface of the mass had a cystic aspect, with
      some hemorrhagic areas between whitish myxoid tissue. Histologically the lesion
      was formed by fibrous connective tissue covered by synovium; focal inflammation
      and hemosiderin-laden macrophages were also present in some areas. At one year
      follow-up the patient is symptom-free.

PMID- 11569081
TI  - Larsen's syndrome: description of one case and review of the literature.

PMID- 11569082
TI  - Quiz. Osteoectasia with hyperphosphotasia (juvenile Paget's disease).

PMID- 11569083
TI  - The use of external fixation in fractures of the tibial pilon.
AB  - The authors report the results of a review of 25 cases of fracture of the tibial
      pilon, treated by external fixation and minimal internal synthesis. Fractures
      were classified according to Ruedi and Allgower; they were: type 2: 11 (of which
      one exposed); type 3: 4 (of which 6 exposed). Complications observed during
      treatment were: pseudarthrosis: 1; osteomyelitis: 2; healing in valgus at 10
      degrees: 2; osteolysis of the distal screws of the fixator: 4; these were all
      resolved with further surgery, except for an osteomyelitis that required
      amputation. Follow-up ranged from 3 to 10 years and clinical and functional
      evaluation, based on the Olerud and Molander score system revealed 80% good (56%)
      and excellent (24%) results.

PMID- 11569084
TI  - Complex fractures of the femur: treatment with a long gamma nail: short- and
      medium-term experience.
AB  - The introduction of the gamma nail and of the long gamma nail, associating the
      principle of intramedullary nailing and of the sliding screw-plate, has led to
      good results in the treatment of complex fractures such as per-sub-trochanteric
      fractures and associated fractures of the femoral neck-diaphysis. In this study,
      our experience with the long gamma nail (Long Gamma Nail Howmedica) is presented.
      Of the 43 patients treated between 1993 and 1998, 21 (49%) with a mean follow-up
      of 2.5 years (1-5 years) were reviewed. Clinical and a radiographic evaluations
      were obtained for each of the patients. This study showed that there was a high
      incidence of poor consolidation (dysmetria in 10 patients, torsion deficit in 7,
      consolidation in varus of the femoral neck in 1 patient) particularly in
      associated fractures of the femoral neck and diaphysis, accompanied, however, by
      good functional recovery (only 3 patients with modification in the angle of
      progression of the foot) and by the satisfaction of the patients questioned.
      Thus, indications for the use of this device in proximal fractures of the femur,
      particularly in elderly patients and in high-energy traumas, are demonstrated.

PMID- 11569085
TI  - A comparative analysis of the different fixation devices used in pertrochanteric
      fractures.
AB  - The effectiveness of four different fixation devices in the treatment of
      pertrochanteric fractures of the femur were evaluated in 147 patients. Based on
      long-term clinical and radiographic evaluation of cases, it is observed that
      although the screw plates, Ender nails, and gamma nail provide satisfactory
      results in the treatment of such fractures, each of these with its own
      indications, the more recent PFN nail, because of its features, seems to adapt
      best to the needs of the orthopaedist.

PMID- 11569086
TI  - The effectiveness of the circular external fixator in the treatment of post
      traumatic of the tibia nonunion.
AB  - Authors report the results they obtained when the Ilizarov circular external
      fixator was used for the treatment of post-traumatic nonunion of the tibia. A
      total of 20 patients were treated. Of these 12 had been submitted to treatment
      elsewhere and using other methods; 9 presented with septic nonunion; 10 revealed
      radiographic findings of atrophic nonunion, and 10 were hypertrophic. There was
      axial deviation in 18 patients. The results of treatment were always: healing of
      the nonunion; functional recovery of the limb; correction of leg length
      discrepancy; recovery of the mechanical axis. The mean stabilization time (days
      between the application and the removal of the fixator) was 138 days. The
      Ilizarov method thus proved that it was effective in the treatment of post
      traumatic nonunion of the tibia where other types of treatment had failed.

PMID- 11569087
TI  - Immediate passive mobilization of the hip after internal fixation of acetabular
      fractures.
AB  - The authors report the results obtained in 16 patients affected with displaced
      fracture of the acetabulum treated surgically and mobilized passively immediately
      after surgery by means of a continuous passive mobilization apparatus for the
      hip. The age of the patients at the time of trauma ranged from 21 to 54 years.
      The posterior wall was involved in 12 cases, while the anterior column was also
      involved in 4. Excellent or good reduction of the fracture was obtained in all of
      the cases. Immediately after surgery, a continuous passive motion apparatus for
      the hip was applied to be used for approximately 3 weeks. At final follow-up,
      which was obtained after a mean time of 5 years, all of the patients except 2 had
      obtained good results. Moderate joint deficit was present in 1 case, while
      sciatic nerve palsy that had already been observed prior to surgery persisted in
      another. Evident radiographic signs of coxarthrosis were not present in any of
      the cases. Based on the opinion of Salter et al. (1980), who in an experimental
      study had observed better healing of the cartilaginous lesions in the joints
      submitted to movement, immediately after surgery we applied a continuous passive
      motion apparatus for the hip in a group of patients affected with fracture of the
      acetabulum. As none of the patient followed-up by us presented evident signs of
      hip arthrosis, the authors hypothesize that continuous passive movement,
      immediately carried out after osteosynthesis, plays a significant role in
      preventing post-traumatic arthrosis of the hip. In truth, small irregularities of
      the acetabular cavity, possibly present after an apparently anatomical reduction,
      could be minimized by the plasmating effect of the head of the femur in movement.

PMID- 11569088
TI  - Infected nonunion of the humerus.
AB  - Eight patients with infected nonunion of the humerus were treated surgically by
      removal of the instrumentation, surgical debridement or wide resection of the
      fracture site and stabilization in compression with an external fixator. A
      monoaxial external fixator was used in 5 patients, a circular external one in 3.
      The amount of time between trauma and treatment described was a mean of 13
      months. Consolidation occurred in all of the patients after an average of 5.5
      months. Long-term follow-up was obtained after a mean of 18 months (minimum 14,
      maximum 35). There was postoperative paralysis of the radial nerve in 2 of the
      cases, with complete recovery after 3 months. One case consolidated despite the
      persistence of a fistula.

PMID- 11569089
TI  - Intramedullary reaming in the treatment of chronic osteomyelitis of the femur and
      tibia.
AB  - The authors comment on the experience acquired in the treatment of chronic
      osteomyelitis of the long bones with intramedullary reaming. The procedure is
      reserved for the femur and tibia with stage I chronic osteomedullary infection
      according to the Cierny-Mader classification. 2 A total of 36 patients were
      treated. Surgical treatment consists in reaming of the medullary canal and in its
      contra-opening with antiseptic solutions. Mean time for lavage is 6 days.
      Criteria for healing involves the absence of clinical, humoral, and radiologic
      signs of active medullary sites of infection. The percentage of healing was
      83.2%, mean long-term follow-up was 2.9 years.

PMID- 11569090
TI  - Nervous lesions as neurologic complications in regional anaesthesiologic block:
      an experimental model.
AB  - The purpose of the study was to evaluate the lesions produced by direct trauma of
      injection needles in the peripheral nervous trunks. Two types of needles were
      compared: one with a tip with a 45 degrees inclination, and one with a tip with a
      14 degrees in clination. Sprague Dawley rats were used, the sciatic nerve of
      which had been subjected to repeated injections under direct vision; the results
      were collected 7, 14, and 21 days after surgery. Both macroscopic and
      histological observation revealed that the greatest injury was produced using
      needles that had a tip with a 14 degrees inclination, that was longer, while
      needles that had a tip with a 45 degrees inclination had a greater tendency to
      slip and rotate at every attempt at penetration.

PMID- 11569091
TI  - Mitotic activity in chondrocyte transplantation from the in vitro phase to the in
      vivo phase.
AB  - The transplantation of devitalized allogenic matrices vehiculating autologous
      chondrocytes, previously isoled and seeded on them could be a solution to the
      problem of repairing lesions of the joint cartilage. For the matrix/cell
      "composite" to be "graftable" the cells must continue to duplicate and produce
      cartilaginous matrix even after transport in vivo. The present study analyzes the
      mitotic activity of chondrocytes planted on devitalized allogenic cartilage and
      grafted in living animals. Chondrocytes of joint cartilage of lambs were isolated
      enzymatically and then seeded in vitro on devitalized allogenic cartilaginous
      matrices for 3 weeks. At the end of the co-culture period, these
      matrix/chondrocyte composites were transplanted in subcutaneous pockets of
      athymic mice. The experimental and control samples were evaluated subsequent to
      explantation by histological study and incorporation of tritiated thymidine. The
      results obtained revealed an important decrease in the values for the
      incorporation of thymidine beginning from experimental time 0 (pre-implant
      evaluation) up to day 28 after implantation, followed by a mild increase at the
      experimental time of 42 days. This study demonstrated the tendency of articular
      chondrocytes cultivated in vitro and subsequently transplanted in vivo on a
      support of devitalized allogenic cartilaginous matrix to modify mitotic activity
      from very high values for the first experimental times, typical of the in vitro
      phases of cellular expansion, to very low values, more similar to the behavior of
      articular chondrocytes in vivo.

PMID- 11569092
TI  - Neurilemmona of the median nerve in a child. Case report.
AB  - A case of neurilemmoma of the median nerve in a child is reported. The rarity,
      the contribution to the diagnosis of the newer imaging methods, especially MRI,
      as well as the good prognosis after a careful enucleation of the tumor, are
      emphasized.

PMID- 11569093
TI  - Proximal chondroepiphyseal injuries of the humerus: a description of three cases
      classified ad Salter-Harris type II.
AB  - Proximal chondroepiphyseal injuries of the humerus constitute a very low
      percentage of traumatic growth pathologies, at around 5% of all fractures during
      childhood. The treatment most commonly used is conservative, with simple
      immobilization; nonetheless, in rare cases where surgery is planned, numerous
      methods of reduction and internal fixation have been proposed. The authors
      propose their experience in the treatment of a small (3 cases) homogeneous group
      (Salter-Harris type II) of proximal chondroepiphyseal injuries of the humerus by
      closed reduction in 2 cases, open reduction in 1, and percutaneous fixation with
      simple Kirschner wires. The results obtained are excellent, without any
      complications or sequelae, and with complete recovery of joint range of movement.
      The authors emphasize the use of this method capable of allowing for early
      mobilization, thus allowing for the child's rapid and non-traumatic return to a
      social life.

PMID- 11569094
TI  - Variations in method in the use of the coracoacromial ligament for the surgical
      treatment of acromioclavicular dislocations.
AB  - Many authors have used the coracoacromial ligament to treat acromioclavicular
      dislocations. The variation in method proposed in this study includes: a)
      detachment of the coracoacromial ligament from the acromial aspect, b) its
      section into two bands, medial and lateral, of which one inserted by means of a
      transosseous hole at the clavicle and the second one anchored bridge-like on the
      clavicle suturing it to the soft tissues; c) temporary fixation of the
      acromioclavicular joint by means of a Kirschner wire or Ghisellini screw pin that
      is threaded at one end. The study conducted may be considered preliminary, as the
      series is constituted by 16 patients affected with grade IV acromioclavicular
      displacement according to Rockwood, acute in 13 cases and inveterate in 3. The
      results which were excellent and good in terms of pain, recovery of range of
      movement, and the subjective opinion of the patients, reveals a subdislocation
      measuring from 3 to 5 mm in 2 patients in our series. Currently, the hypothesis
      may be advanced that the variation in the method described may have the advantage
      of guaranteeing physiological anchoring of the ligament to the clavicle and thus
      providing a greater guarantee should trauma occur in the future.

PMID- 11569095
TI  - Lumbar nerve root compression caused by herniated intradiscal gas: description of
      a clinical case with recurrence.
AB  - The authors report a rare case of recurrence of lumbar nerve root compression
      caused by herniated intradiscal gas treated surgically with resolution of pain
      symptoms. They describe the possible causes of the formation of gaseous material
      reported in the literature. They believe that to avoid recurrence it is important
      to associated removal of the hernia with complete emptying of the disc and
      resection of the posterior longitudinal ligament.

PMID- 11569096
TI  - [Characteristics of N2O emissions from vegetal soils on Fildes peninsula,
      Antarctica].
AB  - The N2O fluxes from the vegetal soils were first measured on the Fildes
      peninsula, Antarctica, and the total N2O emission was also estimated in the
      summer 2 months. The daily variations of N2O fluxes appeared single-peak trend
      under the sunshine or rainy weather conditions but they were irregular under the
      snow weather conditions and inconsistent with the atmospheric temperatures. The
      seasonal variations of the N2O fluxes were affected by the temperature and
      rainfall. The conditions during the transitions between dry and wet seasons
      improved the N2O emission. The total N2O emissions from moss and lichen soils
      were 3.7152 kg and 2.5344 kg, respectively. It follows that the vegetal soils are
      the sources for the atmospheric N2O on the Fildes peninsula, Antarctica.

PMID- 11569097
TI  - [Biodegradation of reactive turquoise blue].
AB  - In this study, the anaerobic degradation and the aerobic degradation of a kind of
      reactive dye--Reactive Turquoise Blue(RTB) were compared. The results proved that
      anaerobic sludge could only decompose RTB in the presence of glucose while
      aerobic sludge decomposed RTB with or without the presence of glucose (RTB of 20
      mg/L was reduced by 37.4% through 24 hours' aerobic treatment with RTB as sole
      carbon source). The enhancement of glucose concentration was beneficial for both
      anaerobic and aerobic degradation of RTB: the anaerobic and the aerobic removal
      efficiencies were respectively 81.5% and 73.6% with RTB of 20 mg/L and glucose of
      1200 mg/L. In the influent RTB concentration also had influence on the activity
      of anaerobic and aerobic microorganisms. When glucose concentration was 800 mg/L
      or 1200 mg/L and RTB concentration was 20 mg/L to 100 mg/L, anaerobic removal
      efficiency of RTB was higher than aerobic removal efficiency by 4.9%-27.2%, which
      meant that anaerobic bacteria is more powerful than aerobic bacteria in terms of
      RTB removal.

PMID- 11569098
TI  - [Relationship between eutrophication control and reservoir operation].
AB  - Choosing Miyun Reservoir as a research background, the spatial distribution
      characteristics of water quality in the reservoir were analyzed, and the
      relationship between reservoir operation and-eutrophication control was
      discussed. With the assistance of water quality model and the monitored data,
      measures that wiping off the nutrients combined with the flood prevention
      operation was proposed. At last, the feasibility of the measure was also
      discussed.

PMID- 11569099
TI  - [Effect of temperature on biodegradation of the petrochemicals in contaminated
      soil].
AB  - Temperature is a significant factor of the natural attenuation of the polluted
      soil. The effect of the temperature on the biodegradation rates and the half-life
      of the petrochemicals in contaminated soil were evaluated in this paper by the
      simulative experiments in laboratory. The results showed that the relationship
      between the temperature and the biodegradation rates was consistent with the
      exponential equation: K = 3145exp(-5233/T). According to the prediction of half
      life of the biodegradation rates by the equation, the half-life at 5 degrees C,
      10 degrees C, 20 degrees C and 30 degrees C were 1499 days, 1075 days, 572 days
      and 317 days respectively.

PMID- 11569100
TI  - [Effect of grazing on microbiological processes of N2O production in grassland
      soils].
AB  - A laboratory incubation study on effect of grazing on microbiological processes
      of N2O production in Aneurolepidium chinese grassland soils by using the
      acetylene-inhibition method was firstly conducted and the seasonal variations of
      related bacteria groups and N2O fluxes were analyzed. Results suggested that
      grazing behavior altered the soil structure which were benefit to microbiological
      denitrification so that N2O emission from this steppe soil was reduced. It was
      the heterotrophic nitrification that is the key microbiological process for N2O
      production in the non-grazing and grazing semi-arid typical grassland soils in
      Inner Mongolia. The reasons why N2O flux from Inner Mongolia semi-arid typical
      grassland soils was lower were also explained in this paper.

PMID- 11569101
TI  - [Degradation of the herbicide dicamba under strictly anaerobic conditions].
AB  - Degradation of the herbicide dicamba was assayed under methane-producing
      condition using a coastal wetland soil as an inoculum. Benzene ring 14C labeled
      dicamba was employed and degradative process proceeds through demethoxylation
      yielding 3,6-dichlorosalicylic acid as the predominant intermediate. The data
      showed that the degradation rate of dicamba by the enrichment culture achieved
      64%, 91% and 95% after 7, 16 and 27 days of incubation, respectively; only small
      quantities of CO2(0.74%) and CH4(0.11%) were recovered with insignificant
      radioactivity. The benzene ring of dicamba was not cleavaged to a significant
      extent. Future cleaning up of dicamba contaminated environment may require an
      effective bioremediation techniques.

PMID- 11569102
TI  - [Full-scale experiment on corn-ethanol production wastewater treatment with the
      thermophilic EGSB reactor].
AB  - Full-scale EGSB reactor was used in the treatment of corn ethanol production
      wastewater that was a typical kind of high strength wastewater in North China. As
      the COD loading rate was as high as 29 kg/(m3.d), the usual SS content was 6000
      mg.L-1, COD removal efficiency remained up to 90%, In addition, the reactor
      started up successfully in only two months with the formation of granular as a
      symbol. Through this experiment, the conclusion was drawn that the EGSB reactor
      is greatly efficient in the treatment of corn ethanol production wastewater.

PMID- 11569103
TI  - [Removing the nitrogen from the ammonium sulfite method paper mill wastewater by
      anoxic/aerobic SBR].
AB  - The experiment results showed that the best technology of removing the nitrogen
      was anoxic time to aerobic time of 1:1.5, a cycle of 8 hours; the SRT should be
      more than 12 d and the loading of NH3-N should be less than 0.063 g/(g.d); when
      the concentration of CODCr, NH3-N and NOx-N was 1200-1800 mg/L, 135-200 mg/L and
      7-10 mg/L respectively, without external carbon sources, the removal rate of NH3
      N and TN could respectively achieve 95% and 66%; after adding sodium acetate the
      removal rate of TN could get to 85%. The addition of sodium acetate at the
      concentration equivalent to theoretical CODCr values of 125 mg/L appeared to be
      the most economical and reliable option.

PMID- 11569104
TI  - [EROD induction in liver microsome of carp(Cyprinus carpio) by nitroaromatic
      hydrocarbons in vitro].
AB  - Nine nitroaromatic hydrocarbons (NAHs) induction of EROD activity was
      investigated by an in vitro assay based on carp (Cyprinus carpio) hepatic
      microsome system. All nine NAHs tested were found to induce the activity of EROD.
      There was dose-effect relationship between EROD activity and concentrations of
      NAHs. It was found that EROD activity was different, when different groups
      substituted at the same position of benzene ring, or the same group was at
      different position of benzene ring.

PMID- 11569105
TI  - [Development of the heterogeneous photocatalytic reactor in water treatment].
AB  - Based on the history and the functions of the heterogenous photocatalytic
      reactors, three categories were discussed. The emphasis was put on the employment
      of the reactors designed for the practice in recent years. It was pointed out
      that the study and the design of the reactors were one of the cores in the
      process of the application of the photocatalytic oxidation techniques. And the
      trend of this technology was also predicted.

PMID- 11569106
TI  - [The composition of PAHs in fly ash in Beijing].
AB  - The composition of polycyclic aromatic hydrocarbons (PAHs) in fly ash samples
      which were gathered from manufacturing district of Shijingshan district and
      residential quarters of Haidian district were analyzed using HPLC/MS technique.
      The differences of the contents of PAHs in fly ash samples from manufacturing
      district and residential quarters were compared. The changes of the contents of
      PAHs of different seasons were discussed. In this study 135 PAHs including 55
      large PAHs whose molecular weights are greater than 300u were detected in fly ash
      sample from manufacturing district. HPLC/MS offset the deficiency of GC/MS which
      can not determine large PAHs directly and can reflect the distribution of PAHs in
      fly ash more roundly.

PMID- 11569107
TI  - [Measurement of chlorodifluoromethane(HCFC-22) in the atmosphere by using an O2
      induced electron capture detector (ECD)].
AB  - Chlorodifluoromethane (CHClF2, HCFC-22), a typical substitute of
      dichlorodifluoromethane(CF2Cl2, CFC-12), which atmospheric concentration was only
      at 10(-12) V/V level. After preconcentrated air sample, O2-Induced method was
      used to enhance sensitivity of ECD response to HCFC-22. When O2 concentration in
      carrier gas was 0.54%, there was the greatest value of S/N(signal to noise) and
      ECD response increased by about 500 times. With the study of other conditions,
      such as selection of the ECD temperature, programing of the column oven
      temperature and carrier gas flow, a practicable analysis method with high
      sensitivity of ECD was established.

PMID- 11569108
TI  - [Emissions of biogenic sulfur gases from wheat fields].
AB  - Emission rates of carbonyl sulfide (COS), carbon disulfide (CS2) and dimethyl
      sulfide (DMS) to the atmosphere from wheat fields treated with different
      fertilizers were measured by using the closed chamber method. The results showed
      that the emission rate of COS, CS2 and DMS was affected by wheat growth and COS
      was absorbed by the plants. DMS and CS2 were the predominant sulfur gases emitted
      from these fields. The diurnal variations of emission rates of COS and CS2 were
      obvious. The sulfur flux in the plot treated with organic fertilizer was higher
      than that in the other plots. The sulfur fluxes from different plots were in the
      range of -1.40 to 0.79 mg.m-2.

PMID- 11569109
TI  - [Estimation of LC50 of chemicals to rainbow trout by fragment constant method].
AB  - A fragment constant model for prediction of 96 h LC50 of chemicals to rainbow
      trout was developed based on measured experimental data of 258 chemicals
      collected from the literature. The accuracy and the robustness of the model were
      discussed. The coefficient of determination of the model is 0.9495 and the mean
      residual is 0.42 log-unit. The model is robust for both individual chemical or
      chemical class.

PMID- 11569110
TI  - [Aluminum toxicity and tolerance in wheat].
AB  - The physiological and biochemical effects of different species of aluminum on the
      wheat Al-tolerant TAM202 and Al-sensitive TAM105 were investigated. The results
      showed that mononuclear Al could be absorbed by both of the two strains. Compared
      with TAM105, however, TAM202 absorbed less aluminum. The pH of the nutrient
      solution rose with the hydroponics of the two-cultivars. The content of proline
      in leaves of TAM105 increased obviously. The contents of protein, hexose and
      uronic acid in cell wall of TAM202 were higher than that in TAM105 under 75
      mumol.L-1 Al. The results indicated that Al can activated the synthesis of some
      components relative to Al-tolerance in cell wall.

PMID- 11569111
TI  - [Degradation of methamidophos by Saccharomyces rouxii WY-3].
AB  - A strain of Yeast WY-3 was isolated from wastewater sample. It is capable of
      utilizing methamidophos as sole nitrogen and phosphorus sources, and also capable
      of utilizing methylamine, ethylamine and ammonium sulfate as nitrogen sources
      except nitrate and hydroxylamine. The yeast could grow in medinm containing 60%
      glucose and was identified as Saccharomyces rouxii WY-3. The strain contains a
      high active acid phosphatase. The crude enzyme was applied to a plate of
      polyacrylanide gel for electrophoresis, then activity was detected as white
      single band. Inhibiting test showed that sodium fluoride could seriously inhibit
      the activity of acid phosphatase to release phosphorus from methamidophos,
      wherease it make no effect on deamination of the strain WY-3 from methamidophos.
      After methamidophos was degraded by strain WY-3, toxity of the pesiticide reduced
      obviously, and its portion intermediate, methanol and inorganic phosphorus, were
      deteted.

PMID- 11569113
TI  - [Quality of aquatic environment at Haihe River and the pollutant fluxes flowing
      into sea].
AB  - On the basis of the data of water quality monitored from 1993 to 1997, the
      pollution indexes of each pollutant was computed. The results showed that the
      pollution at Haihe river was severe. The rank of water quality at all monitoring
      site were between IV and V grade. The main pollution factors were NH3-N, NO2-N
      and organic contaminants. During the 5 years, water quality of Haihe River was
      improved, however, the pollutant fluxes flowing into Bohai Bay, especially CODMn,
      BOD, NH3-N, NO3-N and NO2-N, were increased, they were increased from 1555, 655,
      337, 156 and 25 t.a-1 in 1993 to 8710, 4317, 2516, 1528 and 188 t.a-1 in 1996,
      and sharply decreased to 1331, 973, 572, 355 and 31 t.a-1 in 1997, respectively.
      It may be mainly due to the change of runoff at Haihe River.

PMID- 11569112
TI  - [Bioaccumulation mechanism of red tide alga Prorocentrum micans for heavy metal
      ions].
AB  - Pollution of heavy metal from industrial wastewater is a worldwide environmental
      problem. Biosorption is an effective technology for the treatment of low
      concentration industrial wastewater. The purpose of this study was to evaluate
      the heavy metal uptake capacities of the biomass of marine red tide Prorocentrum
      micans. All red tide biomass used in this study were obtained from cultivation in
      our lab. Batch experimental results showed that living and non-living biomass of
      P. micans killed by CH2O were similar setting property for Cu2+, Pb2+, Ni2+,
      Zn2+, Ag+ and Cd2+. This study indicated that biomass of P. micans has a high
      capacities for above six heavy metal and the kinetics under the conditions
      studied were relatively fast. About 90% of the biosorption occurred within 10 min
      and an equilibrium was reached in 30 min. The Biosorption capacities for heavy
      metal ions were strongly dependent on pH of the solution, and higher capacities
      were obtained at pH around 5 and higher. Bonding and FIR of P. micans
      polysaccharide obtained by the hot water method for Cu2+, Pb2+, Ni2+, Zn2+, Ag+
      and Cd2+ was also studied. The study indicated that -OH and -CONH2 groups were
      active center of biosorption.

PMID- 11569114
TI  - [The influence of ecological factors on simultaneous nitrification and
      denitrification in MBR].
AB  - The influence of dissolved oxygen(DO), C/N and pH on simultaneous nitrification
      and denitrification in the membrane bioreactor was studied. The experimental
      results showed that only under condition that each ecological factor was
      maintained relative steady, simultaneous nitrification and denitrification might
      proceed smoothly. When DO, C/N and pH of feed water was 1 mg/L, 30 and 7.2, the
      removal rate of COD, NH4+, and TN were 96%, 95% and 92% respectively.

PMID- 11569115
TI  - [Kinetic study on photocatalytic degradation of p-chlorobenzoate at different
      light intensities].
AB  - Kinetics of photocatalytic degradation were investigated at different light
      intensities using para-chlorobenzoate as a model pollutant. It was experimentally
      found that the Langmuir-Hinshelwood model could satisfactorily describe all the
      kinetic processes. However, the two crucial parameters involved in the L-H model
      were dependent of the incident light intensity. With elevated light intensity,
      the rate constant, kr, increased whereas the apparent adsorption constant, Ks,
      decreased. Grossly, both kr and Ks-1 were correlated with the light intensity in
      a power law. The experimental discovery implies that the photonic efficiency
      would be much deteriorated with increased radiation intensity although the
      reaction rate can be enhanced. Applying mild light intensity might be one of the
      critical strategies in photocatalytic reactor design to improve the photonic
      efficiency.

PMID- 11569116
TI  - [Measurement of CO2 concentration in the areas with vegetation cover on the
      Fildes peninsula, Antarctica].
AB  - The average CO2 concentration was above 473.5 mg.m-3 in the areas covered by moss
      or lichen, greatly higher than the global average CO2 concentration, implying
      that these areas may be one of the atmospheric CO2 sources. Abnormally high CO2
      concentration was relative with vegetal physiological and ecological characters.
      In the areas covered by moss, the daily variation of the CO2 concentrations was
      affected by sunshine and temperature and it was also different under the
      conditions of the different weathers. Sunshine was the main factors influencing
      the CO2 concentration. The seasonal variation of the CO2 concentration was
      negatively correlated with atmospheric temperature and positively with rainfall
      and air relative humidity. This article first presents the variations of CO2
      concentration and its influential factors under the Antarctic environmental
      conditions, which also presents new information for the further study to the
      Antarctic greenhouse gases.

PMID- 11569118
TI  - [Phosphorus sorption and desorption of agricultural soils under different land
      uses].
AB  - The potential of P loss from soils under different land uses in Taihu Lake
      watershed was evaluated by laboratory experiment. It was shown that although the
      P sorption capacity of paddy soils under oxidized conditions were little lower
      than that of dryland soils the risks of P loss from the former via runoff and
      leaching were lower than that from the latter, because the soil P levels of the
      former were much lower than that of the latter. For most paddy soils the P
      sorption capacity increased and the P release decreased under reduced conditions
      than that under oxidized conditions and this was attributed to the formation of
      amorphous Fe2+ hydroxides which have a greater surface area and more P sorption
      sites than well-crystallized Fe3+ oxides.

PMID- 11569119
TI  - [Effects of pesticide imidacloprid and its metabolites on soil respiration].
AB  - Soil respiration was measured using NaOH absorbing technique. Imidacloprid were
      applied to soil samples at concentration of 0, 10, 40, 100 micrograms.g-1, its
      hydrolysis and photolysis products were applied at 40 micrograms.g-1. The more
      significant effect at higher concentration of imidacloprid was observed. The
      effect of its hydrolysis product was minor than imidacloprid, but the photolysis
      products of 10 min have stronger effect, the effect decreased greatly in 30 min.
      Soil respiration recovered after 13 days. It showed that imidacloprid and its
      metabolites have little effect on soil microorganism.

PMID- 11569117
TI  - [Trihalomethane formation potential (THMFP) of soils in Guangdong Province].
AB  - Trihalomethane formation potentials were analyzed with the lixivia of typical
      soil samples in Guangdong Province. The results showed that the bulk THMFP
      contents of soil lixivia (b-THMFP) range from 0.7 to 36.8 micrograms/g with a
      median value of 10.6 micrograms/g, and the THMFP contents of 0.45 micron filtered
      soil lixivia, representing the THMFP contents of dissolved organic matter (d
      THMFP), from 0.5 to 21.2 micrograms/g with a median value of 3.9 micrograms/g.
      Sample 19 (Calcareous soil) had the highest b-THMFP and d-THMFP while sample 20
      (Purple soil) had the lowest b-THMFP and sample 5 (Latored soil) had the lowest d
      THMFP. In general, suspended organic matter had great contribution to the THMFP.
      The physico-chemical properties, such as organic matter contents and contents of
      various oxides, as well as soil genetic horizon and vegetation are main factors
      dominating the THMFP levels in the soil.

PMID- 11569120
TI  - [Does response of rape to La and critical concentration of La in red earth].
AB  - The effects of different concentration of La added in red soil on the growth,
      yield, content of chlorophyll and peroxidase(POD) activity of rape were studied
      by pot experiments. The results showed that the growth and yield of rape could be
      improved by low concentration of La3+, however there was no significant
      difference between the treatment and the control, and inhibited when the dose
      were more than 300 mg kg-1 and killed after 600 mg.kg-1 La was added. The
      decrease of chlorophyll content and chlorophyll a/b was observed when the
      exogenous concentration of La was more than 15 mg.kg-1. POD activity increased
      gradually with increasing concentration and prolonging reaction. The feasible
      application level of La was suggested to be below 15 mg.kg-1.

PMID- 11569121
TI  - [A new briquetting method for biomass coal and its influencing factors].
AB  - Regarding to the limitation and low economical efficiency of conventional biomass
      coal briquetter determined by its briquetting method, a new briquetting mechanism
      using the linkage function of biomass fiber was established. The effect of
      different coal, briquetting pressure, biomass shape and content, water content on
      new brequtting mechanism was studied preliminarily. The results showed that the
      new mechanism was suitable for varied kinds coal and biomass. The briquette
      mechanical performance was improved as biomass content increased with a
      reasonable low limitation of about 15%. Pure biomass also could be briquetted.
      The briquetting pressure which could consolidate the linkage of biomass fiber was
      no more than 120 MPa. There would be a negative effect at too high pressure.
      Increasing biomass content and decreasing pressure at certain degree could offset
      the negative effect of water content significantly, with a permissive limitation
      over 10% for Datong coal.

PMID- 11569122
TI  - [Effect of anaerobic acidification treatment on nitrogen removal and toxicity
      reduction of coke plant wastewater].
AB  - Coke plant wastewater was treated by anaerobic acidification-anoxic-aerobic (A1
      A2-O) biofilm process and anoxic-aerobic (A/O) biofilm process respectively.
      Toxicity reduction effects of the two processes were compared. The toxicity of
      coke plant wastewater was equal to that of mercury chloride with concentration of
      0.19 mg/L. Its toxicity reduction was related to the removal of organic nitrogen.
      Anaerobic acidification unit acted an important role on removal of both organic
      nitrogen and reduction of toxicity of the wastewater. After treatment by A1-A2-O
      process, its toxicity can be decreased greatly. When HRT was 37.9 hours, The
      relative luminosity of the treated effluent to photobacterium can attain 96.8%,
      that is equal to the toxicity of mercury chloride with concentration of 0.023
      mg/L.

PMID- 11569123
TI  - [Treatment of dying wastewater from a woolen mill with a pilot-scale
      anaerobic/oxic membrane bioreactor (A/O MBR)].
AB  - A pilot-scale (10 t/d) anaerobic/oxic membrane bioreactor (A/O MBR) was used for
      treatment of dying wastewater from a woolen mill. The results showed that when
      COD, BOD5 and color in the influent was 179-358 mg/L, 44.8-206 mg/L and 50-240
      dilution times (DT), the average COD, BOD5 and color of A/O MBR effluent was 20.2
      mg/L, 1.6 mg/L, 25 DT respectively. The removal of COD, BOD5, color, turbidity
      was 92.1%, 98.4%, 60.7% and 98.9% respectively. Each quota of the treated water
      met the gray water standards (CJ25.1-89). The A/O MBR process has many
      advantages, such as stable performance, simple operation, easy management etc.
      The result of this work could be reference for the designing of industrial scale
      A/O MBR process for treatment of the woolen mill wastewater.

PMID- 11569124
TI  - [Super heavy oil produced water treatment by surface flow constructed wetland].
AB  - This paper adopts a new economic technology of treating super heavy oil produced
      water using surface flow reed wetland system. The field test was conducted at the
      average filtration rate of 3.33 cm/d. The average influent concentrations per
      year of COD, Oil, BOD5, TN were 459.16 mg/L, 27.65 mg/L, 33.52 mg/L, 13.74 mg/L,
      and the average effluent concentrations per year of above indices were 77.21
      mg/L, 1.42 mg/L, 3.90 mg/L, 1.60 mg/L, respectively. Its respective removal
      ratios of COD, Oil, BOD5, TN and pH were 83.18%, 94.86%, 88.37%, 88.36%, 7.87
      7.77. Analyses showed that super heavy oil produced water had no obvious effect
      on soil and almost no effect on growth volume and quality of reeds. Results
      indicated that the surface flow reed wetland could provide an efficient
      economical, stable new means of treating super heavy oil produced water.

PMID- 11569125
TI  - Practical considerations for pharmacogenetic testing.

PMID- 11569126
TI  - Collection conundrum: what's the proper procedure for labeling blood tubes?

PMID- 11569127
TI  - Dealing with "false experts" and overconfidence.

PMID- 11569128
TI  - Information technology treads subtly but powerfully through labs.

PMID- 11569129
TI  - New legislation gives hope for an improved Medicare payment system for clinical
      laboratory services.

PMID- 11569130
TI  - Neural tube defects and folic acid knowledge and use in Mississippi women.

PMID- 11569132
TI  - What does it take to move OR automation to the next level?

PMID- 11569131
TI  - Balanced scorecard helps ORs to weigh clinical, fiscal issues.

PMID- 11569134
TI  - PACU crunch can mean backups in OR.

PMID- 11569135
TI  - Temp staff: are they here to stay?

PMID- 11569136
TI  - Managers wring out scrub suit costs.

PMID- 11569137
TI  - What's the solution to wet packs?

PMID- 11569138
TI  - Cross training: how to make it work.

PMID- 11569139
TI  - Can your facility pass a life safety check?

PMID- 11569140
TI  - [Allometry of egg mass, clutch size and total clutch mass in dinosaurs:
      comparison with modern reptiles and birds].
AB  - The author presents for the first time empirical allometrical equations
      corresponding the mass of dinosaurs with the mass of their eggs, clutch size and
      its total mass. Comparison of these equations with those that were proposed for
      modern taxa of reptiles and birds shows that dinosaurs can be characterized by
      intermediate value of allometry index.

PMID- 11569141
TI  - [Evolution of life cycle: models based on optimization of energy allocation].
AB  - A brief history of optimization approach in modern evolutionary ecology is given
      and author's own results concerning life history evolution are considered in more
      details. The problem of evolutionary optimization is formulated in terms of
      mathematical theory of optimal control as a problem of optimal sharing of
      organism's resources between growth, reproduction, repair, and maintenance. The
      Malthusian parameter is used as optimality criterion. This approach allows, in
      particular, to give evolutionary ecological explanations for some well known
      empirical facts such as attenuation of growth with age (law of Bertalanffi),
      acceleration of ageing with age (law of Gompertz), human sexual dimorphism in
      mean lifespan, age and size of maturity.

PMID- 11569142
TI  - [On the problem og higher fungi origin: Florideae hypothesis].
AB  - The history and current state of the hypothesis of the origin of higher fungi
      (Ascomycetes and Basidiomycetes) and red algae from the common ancestor
      (Florideae) were analysed. Initially the hypothesis was based on similarity of
      their vegetative and generative structures (Sachs, 1874; Dodge, 1914; Chadefaund,
      1953, 1972, etc.), but later it was confirmed by ultrastructural data (Demoulin,
      1974; Kohlmeyer, 1975). It appears to be very useful for the study of the
      development of terrestrial flora (Church, 1921; Kohlemeyer, Kohlmeyer, 1979;
      Atsatt, 1988) and regularities in morphological evolution of higher fungi
      (Corner, 1964, 1970; Chadefaud, 1960, 1982, 1984). Description of the order
      Spathulosporales (Kohlmeyer, 1973), combining the characters of Ascomycetes and
      parasitic Florideae, was one of the most important fact leading to the wide
      recognition of the hypothesis in 1970-80s (Cavalier-Smith, 1978; Taylor, 1978;
      Dodge, 1980; Hawksworth, 1982; Goff, 1983; Coff, Coleman, 1985). Today, however,
      Florideae hypothesis is not confirmed by molecular data and replaced by
      alternative hypothesis of Eumycota origin. Summarizing data on molecular
      systematic of fungi, one could affirm with confidence: 1). Chitincontaining fungi
      are closer to multicellular animals and green plants than to Rhodophyta; 2).
      Rhodophyta and Chlorophyta are monophyletic group; 3). There is no single-valued
      molecular data on taxonomic distance between higher fungi, Chytridiomycetes;
      Rhodophyta, Chlorophyta and Metazoa. Thus, the current data could not testify
      against Florideae hypothesis. It is possible to adjust them with the idea of B.M.
      Kozo-Polyansky (1927) about existence of "Chloroflorodeae" group that is original
      for terrestrial flora; the hypothesis about closeness of Chlorophyta and
      Rhodophyta, as well as Chlorophyta and Eumycota, does not contradict molecular
      data (Stiller, Hall, 1997). The author believes that we need molecular study of
      the whole "stem" of chlorobionta, especially groups that are close to its basis.
      It will will help to understand the relationships between Rhodophyta, giant
      conglomeration of "green algae", chitin-containing fungi, Prasinophyceae and
      different groups of zoomastigot with maximal resolution--the level of orders or
      groups of orders. Only such investigation could provide the material for
      molecular support of phylogenetic constructions. Up to moment Florideae
      hypothesis is able to exist together with the other ideas.

PMID- 11569143
TI  - [Chemoattractants of Distyostelium discoideum (Protozoa: Sarcomastigophora,
      Eumycetozoa)].
AB  - The authors summarize data on interaction of protozoan Dictyostelium discoideum
      with folia acid and cyclic adenozinmonophosphate as chemoattractants. These
      substances play role of antagonists in the life cycle of Dictyostelium
      discoideum: one disperses cells in space and another gathers them into groups
      forming and organism. Analysis of interaction between Dictyostelium discoideum
      and environment allows to reveal that Deictyosteliceae has unique mechanism of
      adaptation of shortage of feeding resource--forming of multicellular organism
      with functional differentiation of cells. This mechanism could be found at
      different hierarchical levels of living organisms.

PMID- 11569144
TI  - [Phenomenon of obligate parthenogenesis in rotifer (Rotifera, Bdelloida)].
AB  - A comparative analysis of biological and morphological organization of obligate
      parthenogenous bdelloids and heterogonic monogononts clarifies the specificity of
      bdelloids' environmental adaptation and variability. It is shown that phenotypic
      polymorphism of bdelloids differs from that of monogononts. The heterogonic
      Monogononta are characterized by tremendous phenotypic diversity in body
      structure adapted to different biotopes in continental waters. This diversity is
      reflected also in structure of corona and mastax used as major criteria for
      definition of high range taxa (classes, orders). The polymorphism of bdelloids
      manifests itself in variability of tiny morphological structures connected with
      living in restricted volumes of water, mainly in terrestrial biotopes. Being
      isolated from other Rotifera at the first stages of evolution, bdelloids have
      been specialized for living under extremely unstable terrestrial conditions that
      led to the development of anhydrobiosis and loss of amphimixis. Variability of
      bdelloids is not connected with characters of high taxonomic ranks and has
      principally different nature in comparison with monogononts. Tempo of
      specialization seems to be slower in obligate parthenogenous rotifers than in
      heterogonic ones.

PMID- 11569145
TI  - [State and tendencies in development of floras of man-transformed ecosystems].
AB  - Basing on published data, authors estimate the current state and tendencies in
      the development of man-transformed floras. Special attention is given to the
      flora of cities and such man-transformed habitats, as open-cast mines, dumps,
      hydrotechnical constructions and railway embankments. Floras of man-made forests
      and plant communities of cultivated lands were also analyzed. Structure of
      urbanized landscapes are considered as the aggregates of man-transformed
      landscapes with fragments of natural vegetation. Floras of urbanized areas are
      characterized by high species diversity, inconsistency of species composition and
      diminishing influence of natural vegetation characteristic for particulate zone.
      Species variety and structure of floras of man-transformed habitats depend on
      specificity of substrate, geographical latitude, neighboring natural communities
      and intensity of technical plants exploitation. In the floras of railway
      embankments species of 10 main families are more abundant then those in natural
      ecosystems of the same latitude. Floras of man-made forests are characterized by
      very high species diversity, this type of habitats plays the main compensating
      role. Analysis of segetal floras reveals the replacement of oligotrophic weeds by
      eutrophic ones and the increase in diversity of Poaceae species.

PMID- 11569146
TI  - [Influence of introduced fish Percottus glenii (Odontobutidae, Pisces)].
AB  - Monitoring of 28 waterbodies has been carried out since 1994 in the region of
      reserve "Lake Glubokoe" (Moscow region, Russia). It was revealed that species
      diversity as well as abundance of larval amphibians correlate negatively with
      presence of introduced fish, rotan, Perccottus glenii (Odontobutidae). Newts
      (Triturus cristatus, T. vulgaris) and frogs (Rana temporaria, R. arvalis, R.
      lessonae) as a rule are not capable to breed in waterbodies colonised by rotan.
      In contrast, toads (Bufo bufo) breed successfully in such sites. Larvae of toads
      are comparatively less edible for rotan and pass their metamorphosis. Persistence
      of amphibians to predation of rotan decreases in the row: B. bufo (R. temporaria,
      R. arvalis and R. lessonae), T. vulgaris, T. cristatus. The Crested newt (T.
      cristatus) is the most endangered species and could extinct in next years.

PMID- 11569147
TI  - [Concepts of taxonomy and concepts of biodiversity: the problem of interaction].
AB  - There is, or there should be, an interaction between concepts of taxonomy and
      biodiversity. On the one hand, taxonomy develops some general and particular
      classificatory paradigms, which own diversity is to be taken into account to
      understand the nature of variety of natural kinds. On the other hand, analysis of
      the properties of biodiversity may put forward nontrivial problems for taxonomy
      that cannot be deduced directly from its own statements. From the point view of
      taxonomy, it is argued that the current concept of biodiversity based entirely on
      the species concept is deeply rooted in reductionistic view of nature. It is
      outdated epistemologically and should be replaced by the modern taxonomic concept
      of the hierarchical phylogenetic pattern. Operationally, the latter presumes a
      possibility for each species to be assigned a certain "phylogenetic weight",
      according to its phylogenetic uniqueness. From the point view of biodiversity, it
      is argued that the global biodiversity is a three component entity, as it
      includes, in addition to phylogenetic and ecological hierarchies, a biomorphic
      hierarchy, as well. This calls for taxonomy to elaborate the general principles
      of classification of biomorphs.

PMID- 11569148
TI  - [Diagnosis and stage-related therapy of joint infections].
AB  - BACKGROUND: Our management of septic arthritis is a combination of a stage
      related arthroscopic irrigation, debridement and antibiotic therapy. At the start
      of therapy x-rays of the infected joint, leukocyte rate with differentiation and
      C-reactive protein level are necessary and aspiration of the joint should be
      performed for gram strain and crystal analysis. Additional imaging and laboratory
      tests can be needed for special indications. An arthroscopic staging of the
      initial joint infection has been shown to have prognostic and therapeutic
      consequences. Antibiotic therapy should start after aspirates and biopsy specimen
      have been taken intraoperatively and has to be adapted to the final results of
      the microbiology. Overall, antibiotic therapy is necessary for a period of 4-6
      weeks, unless clinical findings and laboratory tests have returned to normal. A
      transition to oral administration of antibiotics is possible prior to patient
      release. INTRAOPERATIVE TREATMENT: Intraoperatively, the synovial membrane should
      be left intact. There is no indication for the intra-articular use of antibiotics
      and antiseptics. Wound drains are not necessary. If symptoms of infection persist
      under antibiotic therapy, arthroscopic irrigation can be repeated with good
      results.

PMID- 11569149
TI  - [Cervical spine trauma in patients with trisomy 21].
AB  - Atlantoaxial subluxation is predominantly found in trisomy 21. While neurological
      symptoms occur less frequently, fatal atlantoaxial instability with spinal cord
      compression has been described in trisomy 21 after minor trauma of the cervical
      spine. Presenting a special case we could demonstrate that atlantoaxial
      instability has to be ruled out in patients with trisomy 21 suffering from acute
      cervical spine trauma. We further recommend primary posterior fusion if the
      biomechanical stability of the atlantoaxial complex remains unclear after
      clinical and radiological exploration.

PMID- 11569150
TI  - [The importance to generate robot-assisted milled cavities for total hip
      replacement. A comparative experimental study: manual versus robotic
      preparation].
AB  - We present an experimental study to determine the effectiveness of computer
      assisted robotic bone preparation with regard to primary rotational stability in
      comparison to hand broaching. 5 different cementless stems were standardized
      implanted in synthetic femora and measured in a specially designed apparatus
      (displacement in 6 degrees of freedom). In addition the contact areas of the
      stems and the bone were visualized. The S-ROM- and ABG-stems were more stable in
      hand broached femora. The Osteolock-, G2- and Vision-2000-stems were more stable
      in the robot group. The mode of fixation of each implant could be characterized
      in relation to its position and its stiffness (primary rotational stability). The
      contact areas differed in some prosthesis in the way of preparation. The findings
      highlight the current difficulties in creating a perfect match of robotically
      milled cavity and stem geometry to achieve enhanced stability.

PMID- 11569151
TI  - [Value of human recombinant osteogenetic proteins as bone replacement materials
      in lumbar spondylodesis. Results of an animal experiment study].
AB  - Up to now autologous spongiosa may be considered as the golden standard for the
      filling up of bone defects. Because of the limited quantity, complications at the
      extraction place and the increasing problems concerning infections when using
      homologous spongiosa the development of various bone replacement materials was
      intensified during the last years. The development of various osteogenetic
      proteins as well as experimental studies using these proteins represent a main
      point in science at present. It is expected that these substances will lead to a
      qualitative improvement and increase of bone healing. In the presented study
      influence of various osteogenetic substances to bone regeneration was examined at
      30 breeding sheep after a ventral spine fusion of the segment L4/L5 by a dorsal
      approach. Bone defect filling was realized at each 10 animals with autologous
      spongiosa, Bio-Oss as well as the osteogenetic protein 1 (OP-1). To evaluate the
      progress and outcome of the segmental fusion during a post-operative period of 24
      weeks x-ray controls were performed. In the 24th postoperative week after
      euthanasia of the experimental animals x-ray controls as well as computed and
      magnetic resonance tomographies were carried out. The results of 26 experimental
      animals could be analysed. The results were evaluated according to the criterias
      of an own score-system. Compared with autologous spongiosa OP-1 as a biomaterial
      for the fusion of spine-sections led to favorable radiologic results because of
      higher score values concerning the capability of fusion. Our experiences with Bio
      Oss demonstrated lower osteogenetic potency after defect filling with this
      substance. Therefore we cannot recommend Bio-Oss as filling material for the
      fusion in spine surgery.

PMID- 11569152
TI  - [Postoperative morbidity in surgically treated extension fractures of the distal
      radius. A comparative study of dorsal and volar approach].
AB  - The aim of this study was to investigate perioperative morbidity in operative
      interventions in distal radiusfractures, comparing the operative approach from
      volar and dorsal. Only problems, resulting from the operative approach towards
      the distal aspect of the radius, were examined. In a Case-Control-Study, we
      investigated patients with operative by plate-osteosynthesis treated distal
      radius-extensions-fractures. During 3 years we investigated 92 patients. 49 were
      operated with a volar approach, and after changing the operative management,
      consecutive 43 patients with a dorsal approach to the distal radius. Indications
      for operative treatment were not changed. The approach to the distal aspect of
      the radius corresponded to the recent guidelines. Further perioperative
      procedures were identical, including procedures in anesthesiology. Datas of
      patients have been investigated for epidemiology, kind of operations, point of
      time in treatment, duration of operation, X-Ray, immobilisation and time of
      inhospital stay as well as all documented complications. It has been shown, that
      in respect of all criterias, concerning length of operation (106 vs. 83 min),
      intraoperative X-Ray (3.0 vs. 1.65 min) as well as postoperative immobilisation
      (33 vs. 25 days), and documented incidences of complications like secondary wound
      healing (19/49 vs. 0/43) or nerval irritations (13/49 vs. 1/43), the dorsal
      osteosynthesis is definitively to be favored.

PMID- 11569153
TI  - [Selection of subjects: a problem of clinical trials in traumatology. Selection
      effects and the problem of representation as exemplified by a prospective
      randomized trial on whiplash injuries].
AB  - INTRODUCTION: The internal and external validity of studies is endangered by many
      factors, such as selection of subjects for inclusion. Selection bias itself is a
      major problem, but remains unmentioned and probably unexamined in the majority of
      published clinical trials in traumatology. AIM OF THE STUDY: The aim of this
      investigation was to detect effects of subject selection which occurred during
      our own prospective intervention study. The clinical trial compared subjects with
      whiplash injury who were either treated by early mobilization or immobilization
      (soft collar). MATERIAL AND METHODS: Source population, eligible subjects, study
      participants and final study participants were compared for differences on
      various items like age, gender and further sociodemographic as well as crash
      related factors and clinical findings. RESULTS: Between 21.08.1997 and 30.04.1999
      a total of 732 patients was examined and treated after whiplash in our trauma
      department. The options for inclusion were met by 453 patients. While 346 escaped
      from the study, 107 agreed to participate. Of these another 39 patients dropped
      out of the study. Selection effects were detected on two different levels,
      leading to distinct statistical procedures from those proposed in the study
      protocol. CONCLUSIONS: Uncontrolled selection effects could undermine the
      interpretability of the results of clinical trials. Awareness of selection
      effects is mandatory regarding the applicability of these results to subjects,
      other than those in the group of the final study participants.

PMID- 11569154
TI  - [A minimally invasive technique of intramedullary femoral nailing using the RDS
      system. A new technique for insertion of retrograde femoral nail].
AB  - A total of 72 patients with femoral fractures was treated between July 1997 and
      November 1999, 41 of them with retrograde intramedullary fixation. A minimally
      invasive technique was performed in 18 cases using a recently designed retrograde
      dilatator system (RDS) for the insertion of ACE-nail (DePuy), the reaming of the
      femoral canal and the locking of the distal screws. The mean age of the 18
      patients (7 men and 11 women) was 49 (+/- 21) years. 8 type A, 6 type B and 4
      type C fractures of the femoral shaft according to the AO classification were
      observed. 5 of the patients had sustained a severe polytrauma. The mean ISS of
      the total collective was 18 (+/- 19). No nail failed, no infection occurred, and
      no nerve palsies were recorded. The follow-up time was 10 (+/- 7) months. All
      fractures healed uneventfully. 16 patients were mobilized under full weight
      bearing and regained a full range of motion without pain. In 2 cases of very old
      patients nursing was possible without pain. In 5 cases an implant removal was
      carried out in the same technique. The performed minimally invasive technique
      using the RDS minimizes damages to the patella ligament and the articular
      cartilage. It facilitates the control of rotational deformities and length
      discrepancies of the femur also under difficult conditions, e.g. polytrauma and
      obese patients.

PMID- 11569156
TI  - [Loss of correction after dorsal stabilization of burst fractures of the
      thoracolumbar junction. The role of transpedicular spongiosa plasty].
AB  - Short segment pedicle instrumentation for thoracolumbar burst fracture is known
      to fail due to lack of anterior support. Additional transpedicular grafting and
      dorsolateral fusion were offered to prevent its failure. The purpose of this
      study was to analyse the clinical and radiological outcome in two identical
      groups of patients treated with short segment pedicle instrumentation and
      posterolateral fusion with and without inter- and intracorporal transpedicular
      bone grafting. The clinical and radiological results of two identical groups of
      patients with thoracolumbar burst fractures were analysed. 15 patients (2 f, 13
      m), mean age 35 years, were treated with bisegmental fixation with the fixateur
      interne and unisegmental fusion. Further 15 patients (3 f, 12 m), mean age 34
      years, obtained additional intra- and intercorporal bone grafting. The implants
      were removed 15 resp. 13 months post surgery. Latest clinical and radiological
      follow-up was at 61/24 months. The clinical results were identical in both
      groups. Radiological measurements showed a significant loss of correction for all
      three measured angles (vertebral kyphosis, unisegmental kyphosis and bisegmental
      kyphosis) in both groups. However, patients with transpedicular bone grafting
      showed less loss of bony, vertebral kyphosis. Neither dorsolateral fusion nor
      dorsolateral fusion with transpedicular bone grafting could prevent loss of
      angular corrections.

PMID- 11569155
TI  - [Current situation of traffic accidents in children and adolescents. A medical
      and technical analysis].
AB  - HYPOTHESIS: Analysis of the current injury situation in road users not exceeding
      14 years of age involved in road traffic accidents to allow conclusions regarding
      future prophylaxis. METHODS: Traffic accident reports and medical records from
      children (< 15 years of age) were analyzed for the following parameters: Type,
      location and mechanism of injury, Abbreviated Injury Scale (AIS), Maximum AIS
      (MAIS), Injury Severity Score (ISS), Delta-v, collision speed, type and duration
      of treatment. RESULTS: In 12,309 traffic accidents occurring in the area of
      Hannover, Germany between 1985 and 1998, 7.5% (n = 2,317) of the involved persons
      and 10.5% (n = 1,734) of the injured road users were children and adolescents.
      70% sustained MAIS 1 injuries, 28% MAIS 2-4 and 1.5% MAIS 5/6 injuries. The mean
      ISS was 3.38. 30.3% of the injured children were car occupants, 32.1% bicyclists,
      33.3% pedestrians. 30.3% of the children were unrestrained car occupants, 42.1%
      used safety belts designed for adults, 36% used special devices. Half of the
      children in cars remained uninjured, whereas only 8% of the bicyclists and 2% of
      the pedestrians were not injured. Severe injuries occurred in 20% of bicyclists
      and pedestrians at a collision speed less than 30 km/h and in 80% at more than 50
      km/h. Half of those crashes could have been avoided, if the colliding vehicle
      would had driven about 15 km/h slower. CONCLUSION: Children have an especially
      high risk of injury if they are involved in accidents as pedestrians, bicyclists
      and unrestrained car occupants. Besides of improvements of the inner and outer
      car design, the use of adjusted restraining systems and bicycle helmets is likely
      to prevent from severe injuries. Speed reduction is a considerable factor.
      According to our data, the injury severity for bicyclists and pedestrians
      increases progressively when the collision speed exceeds 50 km/h.

PMID- 11569157
TI  - [Principles of intramedullary fracture stabilization. 2. Surgical technique].

PMID- 11569158
TI  - [Surgical treatment of femoral neck pseudarthrosis associated with delayed union
      of ipsilateral femoral shaft fracture].
AB  - A femoral neck fracture combined with an ipsilateral shaft fracture is often
      primarily not diagnosed. The later treatment is technically more difficult,
      because in the choice of operative technique for the shaft fracture the neck
      fracture it was not considered. In this case report the treatment of the shaft
      fracture with a reamed nail, and the secondary stabilisation of the femoral neck
      fracture with screws resulted in a pseudarthrosis of the femoral neck with an
      unfavourable inclination of the fracture plane. Both fractures healed without
      complications after changing the nail against a bridging plate and an
      intertrochanteric osteotomy with correction in two planes.

PMID- 11569159
TI  - [Patellar metastasis of colon carcinoma. A rarity in differential diagnosis of
      acute knee pain. Case report].
AB  - Although bone tumors are often located in the knee area, primary tumors of the
      patella are rare, and patellar metastases extremely rare. Only a few cases were
      reported in the literature originating from different primary tumors, mostly lung
      and breast [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 18, 19, 20, 22].
      There is only one other case description of a colon carcinoma [21]. We present a
      rare case of primary sigma carcinoma and patellar metastasis. Because of the
      increasing rate of colon carcinomas, neoplastic disease must be considered in the
      differential diagnosis in any patient with otherwise unexplained knee pain.

PMID- 11569160
TI  - [Computer-assisted surgery: developments and prospects in 2001. Results of a
      workshop at Schloss Reisenburg, 23-24 November 2000].
AB  - The progress in computer assisted surgery (CAS) is influenced by new technologies
      in imaging as well as by the input of the users. At present, CAS procedures are
      established in dorsal spine instrumentation, prosthetics and long bone surgery.
      Present status and future of CAS was a topic of an expert meeting at the
      Reisensburg castle. Imaging will speed up in the future using multi-detector
      techniques. C-arm navigation will gain more information using the 3D technology
      intraoperatively. CT based navigation procedures are standard in spine and will
      be established in pelvic surgery. CAS in robotics at the moment means the use of
      robot-assistance. A new concept is the modality-based navigated surgery, which
      can be used at various skeletal locations. Visualization of patient data will
      improve using 3D semi-transparencies with real time update. In the future it will
      be mandatory to find algorithms to fuse the different possibilities and
      techniques. A new concept of surgical training is necessary to teach CAS
      procedures. Therefore discussion must go on to improve these systems.

PMID- 11569161
TI  - [Treatment of femoral fractures in childhood. Consensus Report of the 19th
      Meeting of the Child Traumatology Section of the DGU, Munich, 23-24 June 2000].

PMID- 11569162
TI  - [Physician's stand-by service and work time. Decision of the European Court on
      10/3/2000 (Business Signs, C-303/98) on practice of medical stand-by services].

PMID- 11569163
TI  - [Skin burns caused by electrosurgery devices. Legal liability aspects].

PMID- 11569164
TI  - [Reproductive medicine from childhood to adulthood].
AB  - Modern era brought new diagnostic and therapeutic methods to endocrinology and
      changed the approach to many diseases and developmental disorders. Explosion of
      new findings brought about the possibility of examinations on subcellular level.
      Possibility to study structure and function of various genes is not any more the
      futurology. However, still in medicine romain a roas which are considered as less
      important. It is usually assumed that questions of fertility will be dealt by the
      specialist for adults. We suppose that the given problems should be well advised
      by an interdisciplinary co-operating team in the paediatric patients already.
      However, it should be recognised that some reproduction disorders have their
      origin in the early age. The aim of this paper is to give an overview on
      endocrine disorders in relation to reproduction impairments and to outline
      possibilities of co-operation between different specialist treating patients from
      childhood trough adulthood.

PMID- 11569166
TI  - [Will knowledge of the mechanisms of apoptosis lead to new therapeutic
      procedures?].
AB  - Apoptosis (programmed cell death) ensures under physiological conditions cell
      homeostasis. Under pathological conditions excessive apoptosis, premature
      apoptosis or delayed or infinite apoptosis of cell is a sign of various serious
      diseases. Due to intensive research in this field it proved possible to assess
      nowadays at a molecular level a number of pro- and anti-apoptotic factors and
      their function in the process of apoptosis. Apoptosis proceeds by external as
      well as internal pathway. Factors involved in apoptosis are studied from the
      aspect of their possible therapeutic application in tissue cultures, experimental
      animals, and there are already some initial reports from human pathology. Delayed
      or infinite apoptosis is a typical property of tumor cells. So far most attention
      was paid to two ways of apoptosis induction of tumor cells: suppressed
      translation of the antiapoptic factor Bcl 2 by means of an antisense nucleotide
      and induction of apoptosis by TRAIL (TNF related apoptosis inducing ligand).
      Conversely a delay of premature apoptosis gives hope for hitherto untreatable
      neurodegenerative diseases, myelodysplastic syndromes, ischaemic events and some
      severe infections. This is achieved by means of peptides inhibiting caspases.
      Provided that modulation of cell apoptosis will not be associated with
      unacceptable side-effects, it will become a new therapeutic approach in hitherto
      inadequately curable diseases.

PMID- 11569165
TI  - [Metabolic disorders in nonspecific inflammatory bowel diseases].
AB  - The primary function of the gastrointestinal system is to assist the intake and
      further processing of food and liquids. Besides that, it forms an anatomical
      barrier between the external environment and internal milieu. It is also highly
      important for its paracrine and endocrine function. Inflammatory bowel diseases,
      which frequently cause a gastrointestinal failure, form a specific group. Most
      frequently it is the ulcerative colitis and Crohn's disease. Impaired integrity
      of the gastrointestinal mucosa and failure of protective mechanisms lead to the
      increased permeability of the intestinal wall for antigens derived from food,
      saprophytic bacteria and pathogenic microorganisms. When the gastrointestinal
      failure is threatening, factors determining its residual function become more
      important. As decisive reveals the severity and location of the primary disease.
      Previous surgeries and adaptation of the residual part of the gastrointestinal
      system are important, as well as the possibility of peroral or enteral nutrient
      intake. Depending on the presence of risk factors and the degree of residual gut
      function, some complications can be expected: dehydration, mineral disorders,
      symptoms of protein and energy depletion, infection, and multiple organ
      dysfunction syndrome. It is highly important to decide whether the
      gastrointestinal system will be included into or excluded from the process of
      realimentation. Critically ill patients with inflammatory bowel diseases should
      be treated at an intensive care unit.

PMID- 11569167
TI  - [The antiphospholipid syndrome and antiphospholipid antibodies].
AB  - Antiphospholipid syndrome is a rate systemic autoimmune disease characterized by
      widespread arterial and venous thrombosis, recurrent abortion and
      thrombocytopenia. Laboratory tests reveal antibodies against phospholipids. These
      antibodies are detected by functional tests for the lupus anticoagulant, the
      anticardiolipin ELISA, the anti-beta 2-glycoprotein 1 ELISA and ELISA tests for
      antibodies against other cofactors and phospholipids. Pathogenetic mechanisms of
      thrombosis are poorly understood. Diagnostic assays for detection of
      antiphospholipid have not been yet adequately standardized.

PMID- 11569168
TI  - [Can hormonal contraceptives affect plasma levels of IGF-1 and IGFBP-1 in slim
      women with polycystic ovary syndrome?].
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) represents a frequent endocrinopathy
      among fertile women. Ethiopathogenesis of the syndrome is multifactorial and it
      is a subject of scientific discussions. Considered is the possibility of
      intraovarial IGF system disorder affecting maturation of ovarial folicles. The
      aim of our work was to determine effects of peroral contraceptives with low
      androgen progestin on IGF system in PCOS patients and healthy woman controls.
      METHODS AND RESULTS: 14 patients fulfilling diagnostic criteria of PCOS and 7
      healthy controls were included into the study. All persons were examined before
      and after six months lasting administration of monophasic estrogen-progesteron
      contraceptive therapy with 35 micrograms of ethinylestradiol per day and 250
      micrograms of low-androgen progestin norgestimate per day. In PCOS patients low
      increase of basal insulinemia levels occurred (16.3 +/- 4.8 vs. 20.8 +/- 4.8 mU.l
      1, p < 0.05). IGF-1 serum levels were not influenced (230 +/- 70 vs. 235 +/- 112
      pg.ml-1, n.s.), IGFBP-1 serum concentration significantly increased (46.3 +/-
      24.1 vs. 75.6 +/- 24.0 pg.ml-1, p < 0.001). Insulinemia in healthy women also
      slightly increased (15.9 +/- 4.0 vs. 18.4 +/- 4.0 pg.ml-1, p < 0.05). IGF-1 serum
      concentration significantly increased (140 +/- 65 vs. 241 +/- 89 pg.ml-1, p <
      0.001). IGFBP-1 was also higher (45.0 +/- 19.19 vs. 80.0 +/- 15.6 pg.ml-1, p <
      0.001). Influence of the hormonal contraception on the followed parameters was
      estimated using Wilcoxon's test. While BP-1 increase was significant in both
      groups, the increase of IGF-1 was significant only in healthy controls.
      CONCLUSIONS: Increased levels of IGFBP-1 were found in both studied groups of
      women. Women with PCOS had higher serum levels of IGF-1 before the therapy and
      the treatment did not influence it. Contrary to it, in healthy women the
      increased value was observed. Explanation of that finding will become the aim of
      our next study.

PMID- 11569169
TI  - [Analysis of the most frequent mutations in girls with Rett syndrome].
AB  - BACKGROUND: Rett syndrome is an X-linked dominant neurodevelopmental disorder
      affecting 1 from 10,000 to 15,000 females worldwide. The responsible gene,
      encoding methyl-CpG binding protein 2 was recently identified. Methyl-CpG binding
      protein 2 is thought to act as a global transcriptional repressor. In the methyl
      CpG binding protein 2 gene are known 5 prevalent mutations that cause Rett
      syndrome. Four of them are detectable by restriction analysis. In this study we
      present the results of the molecular study of four prevalent mutations in the
      gene for methyl-CpG binding protein 2 in Czech and Slovak patients with Rett
      syndrome. METHODS AND RESULTS: 22 females with Rett syndrome were investigated by
      methods of molecular biology. Restriction analysis and direct sequencing of PCR
      products revealed in methyl-CpG binding protein 2 gene 3 different mutations
      (T158M, R168X, R270X) in six unrelated patients with Rett syndrome. Mutation
      R306C, frequent in Great Britain and Sweden, was not detected in our group of
      patients with Rett syndrome. CONCLUSIONS: The diagnosis of Rett syndrome and
      genetic counselling in affected families should go out from the close cooperation
      of the pediatric, neurologic, and genetic departments with the specialized
      laboratories dealing with the molecular biological diagnosis.

PMID- 11569170
TI  - [Relationship between corneal flap adaptation and its reformation after
      intrastromal photokeratectomy].
AB  - A total of 6682 intrastromal photokeratoablations (LASIK) for myopia of 1.5-16
      diopters and hypermetropia of 1.5-8 diopters are analyzed. Lamellar incision of
      the cornea was formed with a Hansatome microkeratotome and photokeratoablation
      was carried out using a Nidek EC-5000 laser. Primary and secondary deformations
      of a corneal flap and primary and secondary adaptation are defined. During LASIK
      for correction of myopia, the areas of corneal flap and corneal bed can fail to
      correspond to each other. This non-correspondence is the greater, the deeper is
      keratoablation. The corneal flap undergoes several stages of changes during the
      early and remote postoperative periods: primary deformation during lamellar
      incision, primary dysadaptation presenting as various forms of corneal dystrophy,
      and secondary deformation developing under new adaptation conditions. The
      velocity of the corneal flap adaptation depends on its reposition during the
      final stage of the operation, which can essentially decrease the risk of
      complications. The incidence of central dystrophy (pseudodiffuse lamellar
      keratitis) in various methods of the flap reposition varies from 0 to 1.5%.

PMID- 11569171
TI  - [Pathological convolutions of internal carotid arteries as one of the causes of
      visual dysfunction in children].
AB  - Visual evoked potentials (VEP) in response to reverse chess patterns were studied
      in 68 patients aged 7-14 years with pathological convolutions of internal carotid
      arteries and 25 healthy children. The latent period was increased and the
      amplitude of P100 peak decreased in the patients, which was indicative of
      dysfunction of the visual route. VEP changed at early stages of cerebral
      circulation insufficiency. The relationship between hemodynamic parameters and
      VEP values was proven. Increased latent period and decreased amplitude of the
      positive peak are the criteria of neurophysiological significance of pathological
      convolutions in the internal carotid arteries.

PMID- 11569172
TI  - [Significance of congenital mixed viral infection in the pathogenesis of
      retinopathy of prematurity].
AB  - Forty-three infants aged 1-5 months with somatic and neurological diseases,
      including congenital, 18 of these with retrolental fibroplasia (RF) and 25
      without RF were examined. Control group consisted of 36 age-matched infants.
      Based on identification of viral antigens in urine precipitate cells, mixed viral
      infection was diagnosed in 100% patients and 16.6% healthy babies.
      Ophthalmotropic ECHO 11 and 19 viruses were detected in 100% patients with RF,
      28% patients without RF, and 10% healthy babies, while rubella virus was
      identified in 83.3, 60, and 8.3%, respectively. The viruses were detected only in
      association with other enteroviruses: Coxsakie A, B, and entero 69-71. These
      viruses detected in infants with RF were as a rule present in their mothers.
      Maternal anamnesis was in all cases aggravated by high risk indicators of
      vertical transfer of toxigenic enteroviruses to the fetus. The results indicate
      that congenital mixed viral infection (association of ophthalmotropic ECHO and
      rubella viruses with toxigenic Coxsakie and entero 69-71 viruses) is involved in
      the pathogenesis of RF.

PMID- 11569173
TI  - [State of cyclofusion reserves in subjects with normal binocular vision].
AB  - The paper for the first time presents statistically processed data on the
      cyclofusion reserves of subjects with normal binocular vision (25) for different
      age groups: adolescents aged 12-14 and adults aged 18-35 years. Two types of
      tests for evaluating cyclofusion under conditions of haploscopy (sinoptophore)
      are offered. The results can be used as a criterion for evaluating cyclofusion in
      various oculomotor abnormalities: squint, diplopia, and cyclotropia.

PMID- 11569174
TI  - [Hemophthalmos in patients with diabetes mellitus].
AB  - A total of 110 patients with diabetes mellitus with intraocular hemorrhages were
      examined using computer densitometry of ultrasonic beta-scanograms of the eyes.
      Indications for various treatments were determined and the outcomes of
      hemophthalmia predicted, depending on its topography, intensity, and volume of
      blood released into the vitreous. Hemorrhages were located mainly in the
      posterior segments of the vitreous body in diabetics with hemophthalmia. High
      efficiency and good prospects of using objective methods of computer analysis of
      beta-scanograms for evaluating the status of the vitreous and extending the
      diagnostic potentialities of modern ophthalmology are shown.

PMID- 11569175
TI  - [Characterization of immunological parameters of the lacrimal fluid in patients
      with various types of the course of keratoconus].
AB  - Local immunity is analyzed in 81 patients (146 eyes) aged 16-49 years with three
      clinical patterns of keratocone. During long remission, IgG level was the
      maximum. In progressive disease, sIgA and transferrin levels were increased. The
      most pronounced shifts were detected in the patients with acute keratocone:
      increased concentrations of IgM, C3 and C4 complement components, alpha 1
      antitrypsin, orosomucoid, lysozyme activity, and immune complexes. These data
      prompt the development of pathogenetically based approaches to the treatment of
      patients with various clinical immunological types of keratocone.

PMID- 11569176
TI  - [Comparative evaluation of the antioxidant activity of para-aminobenzoic acid and
      emoxipin in the cornea and crystalline lens (an experimental study)].
AB  - Antioxidant effect of paraaminobenzoic acid (PABA) in the retina upon different
      routes of its administration has been revealed previously. In this study we
      investigated the antioxidant effect of PABA in the cornea and lens of rats after
      its parabulbar injection. Antioxidant activity of PABA was compared to that of
      emoxipin. One hour after hypoxic hypoxia the animals were parabulbarly injected
      with PABA solutions (0.007-0.08%) and 1% emoxipin. The eyes of intact animals and
      rats exposed to hypoxia alone served as the control. The levels of lipid
      peroxidation products (hydroperoxide, malonic dialdehyde) and catalase activity
      in the cornea and lens were measured 1, 3, 6, and 11 h after injections. PABA in
      all studied concentrations essentially decreased the elevated levels of
      hydroperoxides and malonic dialdehyde and normalized catalase activity. The level
      of lipid peroxidation products and catalase activity normalized 24-28 h after
      hypoxia, while after PABA it normalized within 2-11 h. Antioxidant activity of
      emoxipin in the lens and cornea was the same as that of optimal antioxidant
      concentrations of PABA (0.02% for the cornea and 0.06% for the lens). Hence, PABA
      in a wide range of concentrations (0.007-0.06%) is characterized by sufficiently
      high antioxidant activity in tissues of the anterior segment of the eye (cornea
      and lens) upon local administration.

PMID- 11569177
TI  - [Effects of gaseous flow containing nitric oxide on the eyeball structures (an
      experimental study)].
AB  - Nitric oxide is one of the main factors of intra- and intercellular regulation in
      the organism. Its vasodilating, antiaggregant, antithrombogenic, antibacterial,
      anticarcinogenic, and immunogenic effects are well known. It stimulates the
      reparative processes in soft tissue injuries. We failed to find reports about the
      role of NO in the wound process in the eyes. The source of NO in our experiments
      was medical air-plasma device Plason. Exposure of the eye to NO-containing
      gaseous flow did not cause changes in the lacrimal pH; NO penetrated through the
      cornea and sclera, exerted no appreciable cytotoxic effect on the surface
      epithelium of the eye, did not change the intraocular pressure, and caused no
      morphological changes in ocular tissues. On the other hand, NO-containing gaseous
      flow had an appreciable lasting effect on the diameter of the conjunctival
      vessels, this effect being dose-dependent. The doses of NO-containing gaseous
      flow which can be used in the treatment of eye wounds were determined.

PMID- 11569178
TI  - [Micro-trephination of the limbus in neovascular glaucoma].
AB  - Microtrephination of the limb was carried out for neovascular glaucoma on 112
      eyes. The technique of the operation is described and its results are analyzed.
      Electric microtrephine (0.6 mm) allows making perforations in the limb as oblique
      microchannels connecting the anterior chamber and the subconjunctival space.
      Mitomycin C, an antimetabolic drug, was used for neovascularization control near
      the channels and filtration pad. High efficiency, low invasiveness, and low
      incidence of postoperative complications recommend this operation as an
      alternative method for the treatment of neovascular glaucoma.

PMID- 11569179
TI  - [Blood-eye barrier in the acute period of experimental severe alkaline burn of
      the eye by injection of deoxyglucose into the central vein].
AB  - The permeability of the blood-eye barrier for 14C-labeled deoxyglucose injected
      intravenously was studied on a model of severe experimental eye burn in 12
      rabbits (24 eyes). The barrier permeability was evaluated by the content of
      radioactive material in the burnt eye humor in comparison with intact eye.
      Analysis of radiometric data showed a significant difference in the content of
      14C in damaged and intact eyes. The permeability of the blood-eye barrier was
      increased in the damaged eye, this permeability depending on the concentration of
      the agent in the blood.

PMID- 11569180
TI  - [Euthyroid Graves' disease (problems of diagnosis and treatment)].
AB  - Twenty-six patients with endocrine ophthalmopathy without signs of thyroid
      disease (according to ultrasonic scanning, measurements of free thyroxin and
      thyrotropic hormone-TTH) were examined. Edematous exophthalmos in the compensated
      stage was diagnosed in 13 patients, subclinical stage of this condition in 10,
      and endocrine myopathy in 3 patients. Russian drug thyroliberin was used for
      accurate diagnosis of thyroid dysfunction; injection of this drugs to normal
      subjects leads to a drastic (3.5-5-fold) increase of TTH level. After measurement
      of TTH, the drug was infused intravenously by jet injection in a dose of 500
      micrograms. Ten normal subjects were controls. 30 min after thyroliberin
      injection, TTH was measured. It was sharply increased in half of patients and in
      the control group. In one-third of cases (mainly with edematous exophthalmos) TTH
      level increased negligibly or even decreased after the test. After 1.5-2 years,
      signs of hyperthyrosis manifested in one-third of this group of patients. The
      authors consider that patients with the so-called Graves' disease are at a high
      risk of thyroid abnormalities and should be regularly consulted by both
      ophthalmologist and endocrinologist.

PMID- 11569181
TI  - [Conservative therapy of isolated retinal vasculitis].
AB  - Isolated retinal vasculitis (IRV) is a form of retinal vasculitis without other
      types of eye inflammation or systemic vasculitis. Treatment of IRV is a difficult
      problem. We report the results of treatment of 43 IRV patients (25 men and 18
      women, mean age 32.5 +/- 5.5 years with a range of 22-42 years). The main therapy
      for IRV were corticosteroids. They were used by pulse therapy, orally and locally
      (periocular injections). Improvement of visual acuity was more pronounced in
      patients treated by pulse therapy (0.35 +/- 0.15) than in those treated orally
      (0.16 +/- 0.06, p = 0.0132) and parabulbarly (0.06 +/- 0.12, p = 0.0009).
      Resorption of retinal perivascular exudate was sooner achieved by steroid pulse
      therapy than by oral treatment (8.1 +/- 2.2 days vs. 17.9 +/- 2.8 days, p <
      0.0000) or periocular injection of steroids (30.9 +/- 7.1 days, p < 0.0000).
      Prednisolone (10-20 mg) was prescribed for 4-12 months in order to prevent IRV
      recurrences. Steroid-resistant patients were treated with cyclosporin A (5
      mg/kg). The treatment was supplemented by fibrinolytics, angioprotectors, and
      antioxidants.

PMID- 11569182
TI  - [Diagnostic criteria in associated strabismus and blepharoptosis].
AB  - A complex method for examining the function of the upper eyelid and oculomotor
      system in patients with strabismus concomitant with ptosis is described. Use of
      this method in 62 patients helped distinguish three clinical forms of this
      abnormality. It allows detecting important diagnostic criteria and determine the
      treatment strategy for this patient population.

PMID- 11569183
TI  - [Azelastine in the treatment of allergic conjunctivitis].
AB  - The efficiency of azelastin (eye drops) in allergic conjunctivitis was evaluated.
      Ophthalmological, specific allergological, bacteriological, and cytological
      studies were carried out in 3 groups of patients. Group 1 was treated with
      claritin (orally), group 2 with azelastin (eye drops), and group 3 with both. The
      treatment was effective in all 3 groups. Regression of the clinical symptoms
      started earlier in groups 2 and 3 and was observed throughout the entire period
      of observation.

PMID- 11569184
TI  - [Involvement of the organ of vision in leptospirosis grippotyphosa].

PMID- 11569185
TI  - [Comparative efficiency of the effects of conservative and surgical methods of
      treating primary open-angle glaucoma on blood supply of the optic nerve and
      retina].

PMID- 11569186
TI  - [Features of concomitant squint developing from birth].

PMID- 11569187
TI  - [Cone dystrophies and dysfunctions].

PMID- 11569188
TI  - [Semax in the treatment of glaucomatous optic neuropathy in patients with
      normalized ophthalmic tone].
AB  - A complex of neuroprotective therapy, including a new Russian neuropeptide semax,
      was used in the treatment of glaucoma patients with normalized ophthalmic tone.
      Electrophysiological and computer methods of examination demonstrated the
      advantages of new therapy over traditional neuroprotective treatment for
      glaucoma. The efficiency is due to pathogenetic activity of semax possessing both
      neuroprotective and neurotrophic effects.

PMID- 11569189
TI  - [Visual functions in personal computer users: ophthalmic-ergonomic aspects].

PMID- 11569190
TI  - [Clinical and morphological bases of inferior exterior tarsopexy].
AB  - Involution processes caused by elongation of the lower eyelid are associated with
      loss of elastic fibers, destruction of collagen fibers, and fibrous degeneration
      of the distal fragment of the tarsal plate. The authors present a morphological
      validation of resection of the lower pedicle of the external ligament of the
      eyelid and shortening of the lateral part of the tarsal plate. Modified suture
      fixation to the orbital external wall periosteum and external retinaculum is
      proposed, ensuring adequate tension of the lower eyelid. High functional
      efficiency of the operation is analyzed on 66 clinical cases; the incidence of
      complications was low and good cosmetic results were attained (period of
      observation 3-52 months).

PMID- 11569191
TI  - The new classification system of periodontal diseases and conditions.

PMID- 11569192
TI  - Clinical efficacy of the Nd:YAG laser for combination therapy using EMD for
      periodontal reconstructive surgery: clinical case reports.

PMID- 11569193
TI  - High-tech paging systems.

PMID- 11569194
TI  - High on hygiene: recall, retention ... and revenues.

PMID- 11569195
TI  - Transform your practice with high technique, Part 3: Perils of low-income, low
      tech practices.

PMID- 11569196
TI  - Practice management software.

PMID- 11569197
TI  - Monitoring blood pressure in the dental office.

PMID- 11569199
TI  - "I scream, you scream". Summer's cold confections can be a pain in the tooth.

PMID- 11569198
TI  - Dentistry takes a hard look at soft drinks.

PMID- 11569200
TI  - More benefits for the buck. Study reveals which healthcare services save more
      lives for fewer dollars.

PMID- 11569207
TI  - Changes in the diagnosis and management of dental caries.

PMID- 11569208
TI  - Hygiene burnout.

PMID- 11569209
TI  - Management of cardiac patients in the dental office.

PMID- 11569210
TI  - ReD Hot hygiene, Part 2: R is for resourceful.

PMID- 11569211
TI  - Cosmetic technique video round-up: time to catch up!

PMID- 11569212
TI  - Emotional intelligence: keys to success in today's dentistry.

PMID- 11569213
TI  - In search of the Holy Grail.

PMID- 11569214
TI  - A new protocol for immediate functional loading of dental implants.

PMID- 11569215
TI  - Stratification: ancient art form applied to restorative dentistry.

PMID- 11569216
TI  - The intuitive guide to shade selection.

PMID- 11569217
TI  - Communicating color.

PMID- 11569218
TI  - More than basic.

PMID- 11569219
TI  - Making waves.

PMID- 11569220
TI  - Nonsurgical endodontic re-treatment, Part 1.

PMID- 11569221
TI  - The importance of drug interactions in dental practice.

PMID- 11569223
TI  - Book 'em. Enterprisewide scheduling presents challenges, but CIOs will find it
      worth the time and effort.

PMID- 11569222
TI  - Choosing a starting point for restorative dentistry.

PMID- 11569224
TI  - On the verge of a unifying link.

PMID- 11569225
TI  - Healthcare innovations in technology systems. Helping hands. Case managers get a
      lift from a Web-based data management tool.

PMID- 11569226
TI  - Warehousing your data. Thinking ahead can ease the transformation.

PMID- 11569227
TI  - [Clinical significance of microbiological monitoring of infective agents in an
      urological hospital in the selection of antibacterial therapy regimens].
AB  - Individual microbiological examination of each patient can improve significantly
      the response of urological patients to antibacterial therapy. 6000 cultures of
      opportunistic microorganisms isolated from patients with various infectious
      inflammatory diseases were studied. Most of them were gram-negative: P.
      aeruginosa, E. coli, Enterobacter spp., Proteus spp. Of gram-positive most
      frequently occurred Staphylococcus spp and Enterococcus faecalis. The cultures
      showed different spectrum of the sensitivity to antibacterial drugs used in
      urological practice. The choice of etiotropic therapy was the easiest in E. coli
      infection, the hardest in P. aeruginosa and Enterobacter pylori infection.
      Combined treatment of complicated urological infections with gentamycin,
      ampicillin, carbnicilline, azlocillin is much more effective than monotherapy. P.
      aeruginosa is more sensitive to cephalosporins, fluoroquinolins, carbapenems and
      combination of aminoglycosides with betalactame drugs.

PMID- 11569228
TI  - [Pathogenetic bases of combined use of physical factors in multimodal treatment
      of patients with chronic prostatitis].

PMID- 11569229
TI  - [Change in anatomo-functional state of the parenchyma in early unilateral renal
      cell carcinoma before and after surgical treatment].
AB  - The aim of the trial was to study compensatory potential of renal parenchyma in
      the presence of renal cell carcinoma (RCC) and after organ-saving and radical
      surgical treatment as shown by one-photon emission computed tomography (OPECT).
      OPECT before the treatment and 6 and 12 months after it evidences that in
      unilateral RCC, irrespective of the focus location, both kidneys as a single
      organ respond to tumor growth with compensatory hypertrophy. Compensatory reserve
      is limited. In tumor size more than 6 cm the affected kidney starts losing the
      volume of the functional tissue while infiltrative growth is most likely.
      Assessment of the compensatory potential of the kidneys provides additional
      information. If the volumes of the kidneys differ by more than 30%, RCC growth is
      infiltrative. In this case only radical nephrectomy is recommended. If the size
      of the kidneys is by 60% more than normal one and parenchymas of the affected and
      contralateral kidney reach their compensatory limit but are equal, indications to
      organ-saving surgery extend as greater hypertrophy of the remaining kidney is
      excluded. After organ-saving surgery, a compensatory increase was observed in the
      contralateral kidney. This is explained by effective distribution of protein
      material and separate processes of proliferation (healing) and hypertrophy
      (compensation). Assessment of anatomo-functional condition of renal parenchyma
      helps better selection of patients for organ-saving surgery.

PMID- 11569230
TI  - [Changes in prostate-specific antigen in casodex (bicalutamide) monotherapy in a
      dose 150 mg/day given to patients with locally advanced and/or advanced prostatic
      cancer].
AB  - Three-month treatment with casodex (150 mg/day) of untreated patients with
      locally advanced and/or advanced cancer of the prostate is well tolerated. The
      only side effect encountered in 9(60%) patients was temporary breast painfulness
      and swelling. Subjective effects consisted of higher activity (in 40% of
      patients), pain relief (in 33.3%), improved urination (in 80%). Objective effects
      comprise: reduction of prostate-specific antigen in 14(93.3%) patients by 150.4
      ng/ml at the average; a rise in testosterone concentration in 12(80%) patients;
      regression of the tumor by more than 50% in 5(33.3%) patients; stabilization and
      partial regression of regional metastases (1 case); stabilization of distant
      metastases (3 of 4 cases). One patient showed progression of bone metastasizing
      in partial local regression of the tumor.

PMID- 11569232
TI  - [Risks and complications of surgical treatment of urinary lithiasis of single
      kidney].
AB  - 163 patients with urolithiasis of the solitary kidney were treated surgically.
      Analysis of causes of postoperative complications (n = 70) and lethal outcomes (n
      = 11) demonstrate that lethal outcomes were in many cases related to exacerbation
      of renal failure, acute calculous pyelonephritis which had provoked sepsis and
      bacteriotoxic shock, acute hemorrhage with hemorrhagic shock followed by
      development of DIC-syndrome.

PMID- 11569231
TI  - [Hormone-resistant epithelial cancer of the prostate].
AB  - The study of the prognostic criteria of hormone-resistant prostatic cancer (PC)
      by specifying expression of androgen receptor protein as well as Bcl-2 and p53
      proteins, apoptosis regulators, has demonstrated that tumor cells of hormone
      sensitive and hormone-resistant PC forms have different variants of
      immunophenotype. Hormone-resistance is typical for tumors from urothelial, basal
      and neuroendocrine PC cells, glandular epithelium cells which lost androgen
      receptors (AR) and tumors consisting of cells which retain AR but simultaneously
      express Bcl-2 and/or p53 genes. The discovery of androgen-resistant cancer from
      glandular epithelium which has immunophenotype characteristics of a hormone
      dependent tumor indicates the existence of other mechanisms of protection against
      apoptosis. The development of hormone-resistant cancer 2.5-3 years after hormonal
      therapy is associated with changes in immunophenotype of tumor cells. They become
      Bcl-2- and/or p53-positive while part of them lose AR. Thus, immunophenotype of
      tumor cells may serve a prognostic marker of hormonal resistance of the tumor and
      dictate the treatment policy.

PMID- 11569233
TI  - [Choice of YAG-Nd mode for conduction of interstitial laser coagulation in benign
      prostatic hyperplasia].
AB  - Basing on the results of fundamental and experimental investigations, we have
      selected the YAG-Nd laser mode for interstitial laser coagulation (ILC) of the
      prostate using laser unit LAMIN-1 made in Russia. The experiments were performed
      on cadaver prostates (3 macropreparations of human prostate 50-80 cm3 in volume).
      The samples were exposed to laser radiation after their immersion into 5% glucose
      solution. Laser worked with impulse frequency 30 Hz, power 30-50 W, time of
      exposure 20-50 s. In exposure 30-40 or 20 s recommended power is 30 or 40-50 W,
      respectively. The resultant coagulation necrosis covers 2.8-2.9 cm3, carbonized
      layer is absent. The above mode was used in 10 operations in 65-85-year-olds. The
      duration of the intervention was 10-15 min maximum. The sites were 3-5 in the
      lateral lobe and 2 in the middle lobe of the prostatic gland. The outcomes were
      followed up for 12 months. The comparison of the mean control values with those
      before the procedure provided the following picture after 12 months: preoperative
      IPSS 21.9 vs 9.3 scores postoperatively; residual urine 140 vs 30 cm3; maximum
      urination rate 6.7 ml/s vs 13.5 ml/s, respectively. For interstitial laser
      coagulation we think it valid to use high laser power and short exposure because
      short duration of the operation, complete hemostasis, minor lesion of the
      urothelium, unnecessary long-term drainage of the urinary bladder minimize the
      risk of intra- and postoperative complications.

PMID- 11569234
TI  - [Diagnosis of bladder cancer].
AB  - Increasing incidence of bladder tumors necessitates development of new techniques
      of early diagnosis. A total clinical system including application of
      ultrasonoangiography proved superior to examination under the gray scale mode.
      The diagnostic and monitoring algorithm makes the system highly effective.

PMID- 11569235
TI  - [Assisted reproductive technologies in urology].
AB  - Since 1996 the authors have examined and treated 42 infertile married couples
      (the husbands had azoospermia). To obtain spermatozoa directly from the testes or
      epididymis and subsequent ICSI, 42 patients underwent 53 interventions: TESE (n =
      38), PESA (n = 10), MESA (n = 5). Spermatozoa were obtained from 32(76.1%) of 42
      patients, fertilization occurred in 21(50%) cases, 10(23.8%) wives got pregnant.
      Assisted reproductive technologies expand potentialities of correcting severe
      forms of male infertility including azoospermia. The armory of the operative
      procedures in male infertility was replenished with MESA, TESE, PESA.

PMID- 11569236
TI  - [Ultrasonic methods and semiotics in patients with vasculogenic erectile
      dysfunction].
AB  - The authors have developed criteria for ultrasonic assessment of cavernous
      bodies, arterial and venous circulation in normal penile vessels and in erectile
      dysfunction in 125 patients; describe modern ultrasound modalities in
      differential diagnosis of various forms of vasculogenic erectile dysfunction
      basing on the experience with 92 patients; validate hydrodynamic role of the
      tunica albuginea in pathogenesis of venocorporal dysfunction and pathological
      venous drainage. Early ischemic signs of arterial insufficiency were revealed.

PMID- 11569237
TI  - [Dalphaz-retard treatment of urination disorders in men and women].

PMID- 11569238
TI  - [Effects of calculi structure on the results of ESWL lithotripsy].
AB  - Structure of stones influences effects and sequelae of extracorporeal shock-wave
      lithotripsy (ESWL). Clinical sequelae of ESWL in oxalate stones are the worst
      because of the fragments size and physical qualities of these stones. Oxalates
      are firm and sharp. Such qualities may cause injury and swelling of the ureter
      when the fragments pass it. A JJ stent and catheter are proposed to prevent
      complications of oxalate stone ESWL in the stones size more than 1.5 cm.

PMID- 11569239
TI  - [Case of urethral cancer in a man].

PMID- 11569240
TI  - [Acute orchitis caused by parotitis in adults].

PMID- 11569242
TI  - [The first isolation of Borrelia burgdorferi sensu stricto in Russia].
AB  - 18 Borrelia isolates obtained from adult ticks of the Ixodes ricinus species,
      collected from different plants in April 2000 in the Khostinsk region of the
      Krasnodar Territory in the vicinity of the health resort of Matsesta not far from
      Sochi, were identified by means of PCR and the analysis of polymorphism of the
      restriction fragments of ribosomal rrf-rrl spacer amplicon. Among them, in
      addition to Borrelia species, found in Russia earlier (B. garinii, B. afzelii, B.
      valaisiana and B. lusitaniae), the classical causative agent of Lyme borreliosis
      (B. burgdorferi sensu stricto) was detected for the first time. The isolated
      strain (lr-4721) is now kept in the collection of the Borreliosis Center of the
      Ministry of Health of Russia (the Laboratory of Infections Vectors at the
      Gamaleya Research Institute of Epidemiology and Microbiology). The probable role
      of this infective agent in infectious pathology in Russia is discussed.

PMID- 11569241
TI  - [Magnetic resonance urography: possibilities and prospects].
AB  - A new technique of urinary tracts visualization--magnetoresonance urography (MRU)
      -for a year (2000) was applied in examination of 25 patients aged 17 to 63 years
      with ureteral concrements (n = 11), ureteropelvic stenosis (n = 10), ureteral
      stenosis (n = 2), urinary bladder tumor (n = 1), Ormond's disease (n = 1). MRU
      provides the same information about the obstruction and dilatation of the urinary
      tracts as excretory urography (EU). In cases of EU contraindication (allergy,
      renal failure) or lack of contrast substance excretion, MRU allows to avoid
      additional invasive diagnostic procedures. It also enables visualization of non
      dilated urinary tracts in medicinal polyuria. Non-invasiveness, no need to
      contrast, absence of radiation load open wide perspectives for MRU application in
      various groups of patients including pregnant women.

PMID- 11569244
TI  - [Functional activity of phagocytizing cells of the female reproductive tract in
      inflammation of the upper part of genitalia].
AB  - 66 women of reproductive age with different course of the inflammatory process in
      the upper section of the reproductive tract (endometritis and salpingo
      oophoritis) were examined. The cell composition, viability and functional
      activity of the phagocytizing cells of cervical and endometrial secretions, as
      well as peritoneal exudate, were studied. The study revealed that these
      characteristics of the phagocytizing cells of the reproductive tract in women
      with the inflammatory process differed from similar characteristics in healthy
      women. Different changes in the functional activity of neutrophils and
      macrophages in the biological fluids under study in different course of the
      inflammatory process were detected.

PMID- 11569243
TI  - [Hormonal correction of the resident microflora of the vagina and uterus cervix
      in women with chronic cervicitis].
AB  - Clinical, microbiological and hormonal examination of women with chronic
      cervicitis revealed lesions in the upper section of the reproductive tract in a
      high proportion of those examined, hormonal disturbances being registered in
      96.7% of women. Dysbiotic manifestations (suppression of lacto- and bifidoflora
      and the excessive growth of opportunistic microorganisms) in the uterus cervix
      and vagina observed in patients with chronic cervititis were not associated with
      the etiology of the inflammatory process. The degree of dysmicrobiocenosis in the
      lower section of the genital tract in women with chronic cervicitis depends on
      the character of hormonal disturbances. The most significant inhibition of the
      resident flora was observed when ovarian dysfunction occurred and less
      significant--in cases of hyperprolactinemia and changes in the level of
      hypophysial hormones. Hormonal disturbances led to contamination of vagina and
      cervical canal with opportunistic microorganisms that was inversely proportional
      to the presence of lactic acid bacteria and bifidobacteria in these organs.
      Complex therapy of women with chronic cervicitis with the use of preparations for
      the correction of hormonal disturbances made it possible to restore the normal
      microflora of the genital tract and to improve the results of treatment.

PMID- 11569245
TI  - [Characteristics of enterobacteria isolated from patients with urogenital
      pathology].
AB  - Species composition and a number of persistence characteristics enterobacteria
      isolated from urine of 42 pregnant and 22 nonpregnant women with pyelonephritis
      (relapse, remission), from prostatic fluid of 225 males and secretions of
      cervical canal of 124 women with urogenital pathology (prostatitis, salpingo
      oophoritis) were studied. The study revealed that enterobacteria, including
      Escherichia coli, prevailed in the structure of uromicroflora (66.7-83.3%) and
      constituted a relatively small proportion among "genital" isolates of
      microorganisms (19.9-22.2%). Male and female sterility and the presence of
      enterobacteria in the reproductive tract of patients were found to be directly
      correlated. Clinical isolates of enterobacteria were shown to possess pronounced
      seroresistance and the complex of persistence characteristics, including
      antilysozyme, anti-intercidal and anticomplementary activity.

PMID- 11569246
TI  - [Immunopathological responses in women with chronic inflammatory diseases of the
      uterus and appendages and their therapeutic correction].
AB  - A total of 145 women with chronic inflammatory diseases of uterus and appendages
      (IDUA) were examined. Bacterioscopy of smears and culture of vaginal, cervical
      canal and uterine cavity contents were performed in all patients. Direct
      immunofluorescence and PCR were used for detection of chlamydiae in scrapes and
      smears and in biopsy specimens taken from endometrium. The number of T
      lymphocytes and their subpopulations, B lymphocytes as well as the level of
      plasmatic cells synthesizing IgA, IgM and IgG and secretory IgA (sIgA), immune
      complexes and C3 component of the complement were determined in biopsy specimens
      of the endometrium. Pathomorphological examination revealed structural changes
      characteristic of the immunocomplex disease (secondary deficiency of sIgA,
      pronounced suppression of IgA production by plasmocytes along with an essential
      increase in the number of IgG synthesizing cells and immune complexes fixed to
      the venule endothelium) were detected. Lectin-histochemical study revealed
      considerable changes in secretory activity of endometrial epitheliocytes
      manifested by severe suppression of bactericidal activity of the uterine mucus.
      The detected disturbances of local protective reactions in the endometrium of
      women IDUA gave grounds for including immunomodulators into the traditional
      treatment scheme. The latter made it possible to increase essentially the
      therapeutic effect.

PMID- 11569247
TI  - [Effect of vaginal Lactobacillus metabolites on biological properties of
      Staphylococcus epidermidis and Escherichia coli].
AB  - The influence of supernatants and cell extracts of vaginal lactic acid bacilli on
      the growth, catalase, antilysozyme and anticomplementary activity of S.
      epidermidis and E. coli was studied. Changes observed in the persistence
      characteristics of these microorganisms were found to develop in different
      directions: in S. epidermidis a decrease in antilysozyme activity was mainly
      observed, while in E. coli the suppression of anticomplementary activity was
      registered. The modifying influence of lactic acid flora, revealed in this
      investigation, is regarded as one of the mechanisms facilitating the formation of
      microbiocenosis and ensuring colonization resistance.

PMID- 11569248
TI  - [Characteristics of urogenital and post-enterocolitis reactive arthritides].
AB  - The immune status and profile of HLA antigens of loci A and B were evaluated in
      159 patients with reactive arthritis. Reactive arthritis was caused by urogenital
      chlamydial infection in 64.2% of cases and by Shigella, Salmonella and Yersinia
      enterocolitica infection in 18.9% of cases. In patients with different etiology
      of the disease some variations in its course and outcome, immune status as well
      as in the HLA antigen profile were established that is indicative of genetic
      determination of the immune response character. The established specific
      variations in the immune and immunogenetic status of patients with reactive
      arthritis of different etiology may be used for improving diagnosis and treatment
      efficacy.

PMID- 11569249
TI  - [Persistence of Escherichia coli recombinant strains in experimental animals].
AB  - Recombinant E. coli strains, obtained by gene engineering techniques and capable
      of producing human alpha-interferon and HIV proteins, were studied. The cultures
      under study were completely eliminated from the body of experimental animals
      (mice) in 48 hours, and generalization of the infectious process took place. The
      study revealed that these recombinant strains had low virulence and were weakly
      adhesive, nontoxigenic and weakly toxic. Thus, the recombinant strains under
      study could be classified with class 3-4 of danger according to the
      "Classification of Strains of Industrial Microorganisms by the Degree of Their
      Danger".

PMID- 11569250
TI  - [Persistent properties of Brucella abortus isolated from various sources].
AB  - Persistence factors in 70 B. abortus strains isolated from different sources were
      studied. Depending on the source of the isolation of B. abortus, the spread of
      their antilysozyme, anticomplementary, antiintercidal activity was determined and
      intraspecific differences in the manifestation of these signs were established.
      The highest spread and manifestation of persistence factors was registered in B.
      abortus populations isolated from brucellosis patients and from cattle.

PMID- 11569251
TI  - [Preliminary division of the Ul'ianovsk region into landscape epidemiological
      areas with regard to ixodes-borne borreliosis].

PMID- 11569252
TI  - [Long-term dynamics and prognosis for tularemia and pseudotuberculosis morbidity
      in the Iaroslavl region].
AB  - The trends and main factors influencing the fluctuations of the levels of
      tularemia and pseudotuberculosis morbidity in the Iaroslavl region were revealed
      by the methods of mathematical statistics (regress analysis, time-series
      analysis, etc.). Tularemia morbidity was 0.467 +/- 0.216 cases (1950-1997) and
      pseudotuberculosis morbidity was 0.979 +/- 0.297 cases (1979-1997) per 100,000 of
      the population. The multiple regression equations permitting the prognostication
      of tularemia and pseudotuberculosis morbidity in the Iaroslvl region were
      derived.

PMID- 11569253
TI  - [Molecular and epidemiologic characteristics of HIV-infection outbreak in the
      Irkutsk region].
AB  - The genetic analysis of the variants of human immunodeficiency virus of type 1
      (HIV-I) circulating among drug addicts in the Irkutsk region was carried out. The
      results of serological tests and comparative evaluation of electrophoretic
      mobility of heteroduplexes (HMA) revealed that all 74 samples under study
      belonged to subtype A. Genetic differences between these viruses did not exceed
      2%. Thus, it was the variant of subtype A prevalent in CIS countries which caused
      the outbreak of HIV infection among drug addicts in the Irkutsk region, but not
      viruses of subtypes B, C or A/E typical for this risk group in relatively nearby
      China.

PMID- 11569254
TI  - [Immune response following administration of multicomponent vaccine VP-4 in
      elderly patients].
AB  - The dynamics of immunological characteristics after the administration of
      polycomponent vaccine B[symbol: see text]-4 to elderly persons, constituting a
      risk group with respect to acute respiratory diseases and exacerbations of
      chronic inflammatory diseases of respiratory organs, was studied. The nasal-oral
      administration of the vaccine induced immunological shifts in the systems of
      local and systemic immunity. The content of the populations of lymphocytes with
      markers CD3, CD4, CD16, CD20 was found to have positive dynamics. Considerable
      shifts in the system of local immunity were registered: the content of sIgA and
      IgA in the saliva greatly increased; in addition, an increase in the titers of
      antibodies to Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli
      was observed in persons with initially low titers.

PMID- 11569255
TI  - [Vaccination of medical personnel against hepatitis B: epidemiological and socio
      economic aspects].
AB  - Epidemiological and social aspects of the vaccinal prophylaxis of medical
      personnel against hepatitis B are discussed on the basis of the morbidity
      analysis in viral hepatitis, the results of dynamic screening for the presence of
      hepatitis B markers and the state of postvaccination immunity. The reactogenicity
      and immunogenicity of the vaccine "Euvax B", as well as the socio-economic effect
      of vaccinal prophylaxis, are evaluated.

PMID- 11569256
TI  - [Apudocytes in experimental cholera vaccination].
AB  - The morphofunctional state of apudocytes in the gastrointestinal tract and
      immunocompetent organs (spleen, mesenteric lymph nodes) of mice immunized with
      chemical bivalent cholera vaccine was studied. The study revealed that the APUD
      system of the intestine and the argyrophil elements of the immunocompetent organs
      of white mice gave a response to the oral administration of commercial cholera
      vaccine. The reaction of the APUD system of the gastrointestinal tract was
      manifested by a significant increase in the number of apudocytes and their
      greater synthesizing activity in the immunized animals during the period of
      maximum immunological transformation of the macroorganism. The immunization of
      mice with Vibrio cholerae facilitated the maintenance of homeostasis in the
      macroorganism and prevented appearance of morphological disturbances in its
      organs and system after subsequent challenge with V. cholerae.

PMID- 11569257
TI  - [Cloning of lysozyme and lysostaphin genes of Staphylococcus aureus and their
      expression in Bacillus subtilis cells].
AB  - The gene of microbial lysozyme (lyz) of S. aureus 118 and the gene of lysostaphin
      (lzf) of S. aureus RN 3239 were cloned and their expression in B. subtilis cells
      was shown. Lysozyme production in B. subtilis recombinant clone pLF14-Lyz,
      obtained as the result of cloning, was 2.5-fold greater than lysozyme production
      in S. aureus wild strain 118. Lysostaphin production in B. subtilis recombinant
      strain pLF14-Lzf which had inherited the cloned genes was approximately equal to
      lysostaphin production observed in S. aureus initial strain RN 3239. The
      production of lysozyme and lysostaphin in the cells of B. subtilis recombinant
      strains was observed at 30 degrees C and pH 5.5, while in S. aureus initial
      strains 118 and RN 3239 bacteria produced lysozyme and lysostaphin at 37 degrees
      C and pH 7.5 respectively.

PMID- 11569258
TI  - [Effect of amyxin--a domestic analog of tilorone--on characteristics of
      interferon and immune status of man].
AB  - The influence of amyxin, the Russian oral analog of tilorone, on the human
      interferon and immune status has been evaluated. As revealed by this
      investigation the administration of amyxin has produced a rise in the content of
      serum interferon, an increase in the capacity of leukocytes and lymphocytes for
      synthesizing alpha- and gamma-interferon, the activation of NK and phagocytizing
      cells of peripheral blood. No essential influence of amyxin on the amount of B
      and T lymphocytes, their subpopulations and the levels of the main classes of
      immunoglobulins has been established.

PMID- 11569259
TI  - [Comparative evaluation of the neutrophilokine-inducing activity of Yersinia
      pestis EV and Escherichia coli lipopolysaccharides].
AB  - As shown in this study, neutrophilokine-inducing capacity of Y. pestis EV
      lipopolysaccharide (LPS) was not inferior to, and in secondary immune response
      even exceeded, that of E. coli LPS. Neutrophilokines synthesized under the action
      of the former preparation produced greater influence on the inhibition of
      macrophage migration from the focus of infection, the phagocytic activity of
      these cells (in secondary immune response) and the labilization of the lysosomic
      membranes of macrophages than neutrophilokines induced by E. coli LPS. Only in
      primary immune response the digestive capacity of macrophages was more actively
      stimulated by neutrophilokines induced by E. coli LPS. Both preparations did not
      induce the secretion of neutrophilokines regulating the expression of Fc
      receptors on the surface of macrophages.

PMID- 11569260
TI  - [Production of monoclonal antibodies to T-independent type 2 antigens with
      OptiMem-Iscove medium].
AB  - To obtain monoclonal antibodies to T-independent antigens of type 2, having low
      immunogenicity and incapable of inducing the appearance of memory cells, the use
      of the medium OptiMem-Iscove (1:1) with 10% of fetal serum, glutamine (50 mM) and
      antibiotics (100 units/ml) is proposed. The main advantage of this medium is the
      possibility of cloning cells without the use of feeders. The method has been
      approved in the process of obtaining monoclonal antibodies (McAb) to TI-2
      antigens, both bacterial (S3) and synthetic (PVP), as well as to McAb to T
      dependent antigen (alpha-chains of human IgA).

PMID- 11569261
TI  - [Role of cockroaches Blatella germanica in the development of atopic bronchial
      asthma].
AB  - The results of the development of manufacturing technology for the preparation of
      allergen from the bodies of cockroaches and the physico-chemical characteristics
      of this allergen are presented. The complex allergological examination of
      patients with atopic bronchial asthma revealed that 69.3% of such patients were
      sensitized to house dust, and in 68.4% of them IgE antibodies to cockroach
      allergens were detected. Patients with atopic bronchial asthma, not sensitized to
      house dust, were found to have sensitization to Blatella germanica in 12.2% of
      cases.

PMID- 11569262
TI  - [Formation of intestinal microflora in children during the first year of their
      life].
AB  - In 525 young children the state of intestinal microbiocenosis was studied every
      month of the first year their life. The study revealed that the process of the
      microflora formation lasted throughout the first year of their life and was
      characterized by dysbiotic disturbances. During this period the aggravation of
      dysbiotic changes in the intestine of these children on months 3, 6-7 and 11-12
      was of particular importance. The formation of stable dysbacteriosis led to a
      decrease in the immunological status of the child, which was manifested by the
      increased content of such microorganisms as hemolytic cocci, Proteus and a
      decrease in the quantitative level of bifidobacteria in the total intestinal
      microbiocenosis by the end of the first year of child's life.

PMID- 11569263
TI  - [Antigen 8 biosynthesis during cultivation of Burkholderia pseudomallei and B.
      mallei].
AB  - The dynamics of the antigen 8 synthesis in Burkholderia pseudomallei and B.
      mallei under conditions of their submerged was studied. Differences in the
      intensity of this antigen synthesis in two pathogenic Burkholderia species were
      established and the producer strains, most effective with respect to this sign,
      were selected.

PMID- 11569264
TI  - [Methodological aspects of serological diagnosis in leptospirosis].
AB  - The results of serological study for leptospirosis of 515 blood serum specimens
      from patients coming to different clinics of the Republic of Bangladesh, are
      presented. The sera were tested in microagglutination test. To exclude intergroup
      reactions and to enhance reliability of results, immunoglobulin classes were
      determined with the use of cysteine as a reducing agent and immunoabsorption
      test. In 51 patients (9.9%) antileptospiral antibodies were detected in titers
      from 1:20 to 1:1600 against pathogenic leptospires of different serological
      groups.

PMID- 11569265
TI  - [The role of Chlamydia pneumoniae in etiology of acute bronchitis in children].
AB  - During examination of 60 children aged 3-15 years with manifestations of acute
      bronchitis Chlamydia pneumoniae antigen was detected in their nasal and pharynx
      smears in 11.7% of cases with the use of enzyme immunoassay and indirect
      immunofluorescence test. In 10% of cases chlamydial pneumonia was diagnosed
      serologically. In the course of complex laboratory diagnostics C. pneumoniae was
      detected in 13.3% of cases. The most complete information could be obtained by a
      combination of different methods of the antigen detection as well as specific IgG
      and IgM antibodies.

PMID- 11569266
TI  - [Circulation of respiratory viruses in Moscow and their role in acute respiratory
      diseases morbidity].
AB  - Statistical data obtained during prolonged investigations on the structure of
      infective agents isolated from patients with acute respiratory diseases (ARD) in
      Moscow in 1989-1999 were analyzed. The study revealed that fluctuations of ARD
      morbidity rates were linked with the prevailing circulation of one or another
      type of the virus. The absence of the dominating role of influenza viruses was
      confirmed. The conclusion was made on the necessity of using, in addition to
      influenza vaccinal prophylaxis, chemoprophylactic interventions to maintain ARD
      morbidity on the acceptable level.

PMID- 11569267
TI  - [Morbidity and prophylaxis of hemorrhagic fever with renal syndrome in the
      Republic of Bashkortostan].
AB  - The brief retrospective analysis of morbidity, epizootological data and
      preventive measures with respect to haemorrhagic fever with renal syndrome (HFRS)
      during the whole period of its registration on the territory of the Republic of
      Bashkortostan along with the structure of HFRS morbidity during epidemic seasons
      of 1998 and 1999 is presented. The main causes of decreased HFRS morbidity in
      1998, its rise in 1999 as well as prognosis for the year 2000 were detected. The
      level of HFRS morbidity among the population was found to be directly related to
      the number of rodents and their infection rate. The basic strategy of epidemic
      control interventions has been proposed.

PMID- 11569268
TI  - [Pneumococcal and chlamydial infections in a closed community].
AB  - An epidemic outbreak of acute respiratory infection (295 patients) in an
      organized group of young people was observed in December-May 1997-1998.
      Pneumococcal etiology was established by means of indirect immunofluorescence
      reaction in cases of outpatient pneumonia (81.9%), acute bronchitis (80%) and
      acute respiratory diseases (92.5%). Respiratory chlamydiosis caused by Chlamydia
      pneumoniae was detected in enzyme immunoassay with the use of immunoComb
      Chlamydia Bivalent IgG in patients with pneumonia (66.7%), acute bronchitis (60%)
      and acute respiratory diseases (50%). Synergic relationship between pneumococcal
      and chlamydial infections was noted.

PMID- 11569269
TI  - [Epidemiological effectiveness of influenza immunoprophylaxis with Unifluvax
      vaccine in organized groups of servicemen].
AB  - The results of vaccination carried out in an organized group with the subunit
      influenza vaccine "Influvax" are presented. In the immunized group the registered
      morbidity level exceeded the annual morbidity level by 7-12% only against the
      expected epidemic rise. Respiratory diseases in this group took a mild course.
      The morbidity level in the control group corresponded to the predicted value and
      exceeded the morbidity level in the vaccinated group 4.2-fold. The conclusion was
      made on the effectiveness of immunoprophylaxis.

PMID- 11569270
TI  - [Study of the intestinal microflora in residents of the city of Vladikavkaz].
AB  - Microbiological study revealed high occurrence of dysbacteriosis with the
      decreased amount of Escherichia coli (80.9%) and the presence of E. coli
      hemolytic forms (76.6%). Rather often the elevated content of E. coli with
      decreased fermentative properties was noted (51.1%). In all cases E. coli with
      decreased biochemical activity had hemolytic activity, which was accompanied by
      the deficiency of bifidobacteria (79.2% of cases) and the combined deficiency of
      lactic acid bacteria and bifidobacteria (75% of cases).

PMID- 11569271
TI  - [Bacterial pathogenicity islands].
AB  - The information on the key pathogenicity factors of uropathogenic and
      enteropathogenic Escherichia coli, Shigella, Salmonella, Vibrio cholerae,
      Yersinia, Listeria and Helicobacter pylori is reviewed. The analysis of data on
      pathogenicity "islands" and "islets" of infective agents is given. The problems
      of the genetic control of pathogenicity factors and the functions of
      pathogenicity "islands", found in infective agents, are discussed.

PMID- 11569272
TI  - [Production of stable Bacillus thuringiensis suspensions in an electromagnetic
      apparatus].
AB  - The experiment demonstrated the podibility of obtaining stable suspensions of B.
      subtilis, a microorganism used as an experimental model, in an electromagnetic
      apparatus with a bilateral inductor. The optimum conditions of obtaining such
      suspensions were chosen, these conditions excluding the inactivation of the
      bacteria used as a model in the course of the process. Suspensions containing 75%
      of culture fluid were shown to have the highest stability during prolonged
      storage. Suspensions on the basis of the crystal-forming bacteria B.
      thuringiensis sp. kurstaki, strain Z-52, used in the production of
      entomopathogenic preparations and characterized by high stability and good
      viability in the process of storage were prepared under the selected conditions.
      The apparatus used in these experiments was recommended for use in the technology
      of the production of biopreparations of the basis of the above-mentioned
      bacteria.

PMID- 11569273
TI  - [Evaluation of a method for the serological identification of Vibrio cholerae non
      01].
AB  - The development of a method for serological identification of toxigenic and
      nontoxigenic V. cholerae non-O1, as well as on their role in human pathology, is
      reviewed. The evaluation on this method when used for establishing the etiology
      of acute diarrhea cases and analysis of sporadic diseases and group outbreaks of
      alimentary toxicoinfection type. Different points of view on the formation of
      toxigenic clones of V. cholerae non-O1 in nature is considered. The necessity for
      further development of the serological typing method is substantiated and the
      tasks of its improvement are set.

PMID- 11569274
TI  - [Anaerobic microflora of the female reproductive tract].
AB  - The microflora of the female reproductive tract is very diverse and plays an
      important role in both normal and pathological states. The data on the mechanisms
      of colonization resistance which involve the vaginal microbios (the production of
      H2O2, organic acids, bacteriocin-like substances, competition for adhesion sites)
      are presented. The data on the role of individual antagonistically active
      substances of anaerobic bacteria in suppressing gonococci, fungi, microorganisms,
      associated with bacterial vaginosis, etc. are given. The leading role of
      anaerobic microorganisms in the appearance of microecological disturbances,
      including bacterial vaginosis, is emphasized. The role of the pathogenic
      properties of anaerobic bacteria for the development of different pathological
      processes, such as premature birth, postnatal and postoperative purulent septic
      diseases, inflammation of pelvic organs, cancer of the neck of uterus, is
      discussed.

PMID- 11569275
TI  - [Spectrum of microflora isolated from various areas of the female reproductive
      tract].
AB  - The composition of microflora in different sections of the reproductive tract of
      women with disturbances of reproductive function was studied. The study revealed
      that the spectrum of microorganisms isolated from a bioptic specimen taken from
      the cavity of the small pelvis was narrower in comparison with such spectrum in
      material aspirated from the uterine cavity. The latter was narrower in comparison
      with that in the microflora of the lower sections of the reproductive tract. The
      possibility for one and the same patient to have both similarities and essential
      differences in the spectra of microflora in different sections of the
      reproductive tract was shown.

PMID- 11569276
TI  - [Characteristics of changes in microbiocenosis in patients with chronic
      nonspecific urethritis].
AB  - The species composition and the complex of biological characteristics of
      microflora in the front section of urethra in healthy males and in patients with
      chronic nonspecific urethritis. The study revealed that in patients with chronic
      nonspecific nongonococcal urethritis changes in the microbiocenosis of the
      urethra were observed. These changes were manifested by a decrease in the number
      of species, the appearance of Grain-negative enterobacterial flora and an
      increase in the persistence potential of symbiotic bacteria. These disturbances
      are regarded as the manifestation of urogenital dysbiosis.

PMID- 11569277
TI  - [Factors of the local immune defence of the reproductive tract in pregnant women
      with vaginosis].
AB  - Clinico-immunological examination of 99 pregnant women with diagnosed vaginosis
      and 132 pregnant women without genital infection as a control group, was carried
      out. The immunological factors of cervical and vaginal secretions in pregnant
      women before and after local treatment were studied. The conclusion was made that
      the established changes in the cell-mediated and humoral factors of the immune
      resistance of the reproductive system could probably play some pathogenetic role
      in the development of vaginosis and its relapses in pregnant women. As found in
      this study, more pronounced changes in the local factors of immune protection
      (the signs of the functional irritation of neutrophils in combination with the
      prevalence of sIgA and lysozyme simultaneously with a decrease in the level of
      IgM and IgG in cervical slime) developed in patients with subsequent relapses of
      vaginosis, these changes remaining after local treatment. The defects of cell
      mediated and humoral factors of cervical and humoral secretions, together with
      some clinical parameters, were shown to be prognostically unfavorable with
      respect to the relapses of vaginosis in pregnant women.

PMID- 11569278
TI  - [Etiology and systemic immunity disturbances in patients with tuboperitoneal
      infertility].
AB  - The etiological structure of the inflammatory diseases of genitals at different
      levels of the reproductive tract of women with tuboperitoneal sterility was
      studied. The study revealed the prevalence of cocci in the cervical canal,
      anaerobes in the endometrium and chlamydiae in the abdominal cavity (peritoneal
      fluid, the ovarian capsule, fimbriated ends), as well as the presence of mixed
      infection in 27% of the patients under study. The specific features of immunity
      in women with tuboperitoneal sterility were established, which determined the
      main trends of the subsequent pathogenetically oriented immunocorrection.

PMID- 11569279
TI  - [Effect of radio wave-induced hyperthermia on microflora of the prostate in the
      treatment of prostatitis associated with infertility].
AB  - The influence of hyperthermia induced by radiowaves on the microflora of the
      prostate in cases of male sterility was studied. The use of hyperthermia was
      shown to produce a stable decrease in bacteriospermia and the persistence
      potential of bacteria isolated from sperm. Hyperthermia produced a bactericidal
      effect not only on microorganisms contained in sperm but also on the microflora
      of prostatic tissues 1 cm deep. The study gave grounds for treating male
      sterility with the use of hyperthermia induced by radiowaves and a subsequent
      course of antibiotics to achieve the stable decrease of bacteriospermia and the
      restoration of the reproductive function.

PMID- 11569280
TI  - [Characteristics of the population and subpopulation composition of peripheral
      blood lymphocytes in noncomplicated pregnancy based on flow cytofluorometry
      data].
AB  - The population and subpopulation composition of peripheral blood lymphocytes of
      33 women was studied in the dynamics of non-complicated pregnancy by the method
      of flow cytofluorometry with the use of equipment and reagents supplied by Becton
      Dickinson, Inc. This study revealed that the non-complicated course of pregnancy
      was characterized by the adequate reaction of the mother's immune system ensuring
      the physiological development of the fetus during pregnancy and timely labor.

PMID- 11569282
TI  - The decision to donate.
AB  - This country's critical shortage of transplantable organs leads to the deaths of
      more than 4,000 patients awaiting transplants every year, which amounts to 12 or
      13 deaths per day. While the potential number of organ donors in the United
      States ranges from 8,000 to 15,000 each year and numbers indicate that most
      people support the idea of organ donation, only about 5,500 deaths in the United
      States result in organ donation annually.

PMID- 11569281
TI  - Forecasting the future of managed care.
AB  - Recently Uwe Reinhart, the noted Princeton University health economist, speaking
      at the Michigan Health Policy Forum, pointed out that the health care system in
      the United States has always been managed; how it is managed and by whom is what
      changes. The demand continues for a mechanism to coordinate the delivery and
      control of health care costs. Managed care isn't dead, but it is likely to change
      significantly in the future from what we understand it to be today.

PMID- 11569283
TI  - Dodging the bullet: the case for pre-employment testing.
AB  - For most people, taking a test is like listening to modern music: you have no
      idea what the heck they're talking about and you're glad when it's over.
      Nonetheless, testing is a right of passage in our culture that often represents a
      doorway to better things, such as a job.

PMID- 11569284
TI  - More blockbusters on the way. Pharmaceutical spending and the impact of pipeline
      drugs.
AB  - Prescription drug spending continues to increase annually and continued growth is
      expected over the next few years, fueled by potential blockbuster drugs currently
      being developed by pharmaceutical manufacturers. In 2000, Blue Cross Blue Shield
      of Michigan (BCBSM) prescription drug expenditures for Michigan residents
      represented 26.4 percent of total BCBSM payments, while payments for inpatient
      hospital services accounted for 19.7 percent of total BCBSM payments.

PMID- 11569285
TI  - Successful strategies in changing roles.

PMID- 11569286
TI  - Michigan Harvest Gathering creates a sense of family.
AB  - In 1998, the MHA became the primary sponsor of the Michigan Harvest Gathering
      food- and fund-raising drive to help the Food Bank Council of Michigan (FBCM) and
      its 12 regional food banks.

PMID- 11569287
TI  - Managing investment risk.
AB  - The S&P was down 10.1 percent last year. The MSCI EAFE Index was down 15.2
      percent and the NASDAQ was down, too--by 39.4 percent for the year! So far this
      year, the S&P has lost 11.3 percent, the MSCI EAFE is down 18.2 percent, and the
      NASDAQ is down 20.8 percent. Is it any wonder that managing investment risk has
      reasserted itself as an integral part of the investment process?

PMID- 11569288
TI  - Healing the body, mind and spirit.
AB  - Hospitals are, first and foremost, places that function to treat what ails the
      body. But for those who are not well and their caregivers, hospitals should also
      offer a source of comfort to the mind and spirit. In response to that need,
      Sparrow Health System of Lansing has created a special place for their community
      to go to heal.

PMID- 11569289
TI  - Recruitment and retention (A.K.A. restoration and renewal!).
AB  - Over the past decade, health care has been in a whirlwind of dramatic confusion
      due to the speed and magnitude of changes in the industry. This situation has
      been a source of consternation for health care providers as well as chief
      executive officers and administrators. Medicine and healing is currently
      entrenched in an unbalanced and unchecked environment.

PMID- 11569290
TI  - Knowing is most of the battle.
AB  - Colorectal carcinoma is the fourth most frequently diagnosed cancer and second
      most frequent cause of death from cancer in the United States. Each year in
      Michigan, more than 5,000 people are diagnosed with invasive colorectal cancer,
      and more than 2,000 persons die from this disease.

PMID- 11569291
TI  - Brother, can you spare a dime?
AB  - According to former Colorado Gov. Richard Lamm's sometimes controversial take on
      American health care, "We are inventing the unaffordable and spending the
      unsustainable. We need to focus limited resources where they will buy the most
      health for society."

PMID- 11569292
TI  - Living on the banks of denial.
AB  - American expectations for health care over the last 30 years have been developed
      during the most massive transfer of wealth into one sector that history has ever
      seen. American expenditures for health have been growing for the last 40 years at
      two and one half times the rate of inflation, which defies the law of economic
      gravity. Health care has grown from 6 percent of our gross domestic product (GDP)
      to almost 14 percent in 40 years and now accounts for one dollar out of every
      seven dollars spent in America. Americans pay 50 percent more per capita for
      health care than the average of the rest of the developed world. If US health
      care were a separate nation, it would have one of the largest economies in the
      world.

PMID- 11569294
TI  - The treatment of gastroesophageal reflux disease with proton-pump inhibitors and
      its implications on managed care--clinical overview of gastroesophageal reflux
      disease. Roundtable discussion.
AB  - The importance of gastroesophageal reflux disease (GERD) to managed health care
      systems cannot be overestimated. It contributes significantly to the use of
      health care resources, including doctor's services, medication consumption, and
      diagnostic testing. A roundtable meeting of 13 managed care experts was convened
      January 23, 2001 in Dallas, to discuss the implications of GERD on the managed
      care system. The following proceedings are published in five sections. In the
      first part, Jeffrey Danzig, MD, a gastroenterologist, provides the clinical
      foundation for the discussion, based on the existing literature and his personal
      practice.

PMID- 11569295
TI  - The treatment of gastroesophageal reflux disease with proton-pump inhibitors and
      its implications on the Henry Ford Health System.

PMID- 11569296
TI  - The treatment of gastroesophageal reflux disease with proton-pump inhibitors and
      its implications on managed care--pharmacoeconomics and its application to
      antisecretory drugs: a case study.

PMID- 11569299
TI  - Clinical sensitivity: the inseparability of ethical perceptiveness and clinical
      knowledge.
AB  - This article argues that there is an important connection between ethical
      sensitivity and clinical competency in nursing. This is more than a defense for
      ethical attitudes and virtues in clinical practice, however. I will show in what
      way ethical sensitivity is important not only to moral judgment, but to
      professional clinical knowledge and judgment as well. Drawing on central insights
      from continental philosophy, Husserl, Heidegger, Levinas and Foucault, as well as
      classical virtue theory, the article elucidates the inseparability of ethical
      sensitivity and clinical knowledge in nursing. Ethical sensitivity has bearing
      upon clinical knowledge and awareness in two important ways. First, what we
      consider relevant clinical knowledge and therapeutic measures frequently
      encounter the realities of clinical conditions, realities which embody certain
      moral qualities and appeal to moral values. In clinical nursing, it is important
      to understand how this encounter between professional knowledge and moral values
      informs clinical action, making it morally as well as professionally proper.
      Second, sensitivity to vulnerability qualifies clinical knowledge in the way that
      it alerts clinical sensitivity altogether. Perception of morally salient features
      informs the nurse about significant changes in the patient's pathological
      condition. The ability to be touched morally by the patient's condition, his or
      her vulnerability or vitality and positive experience is epistemologically and
      prognostically significant.

PMID- 11569300
TI  - The relationship of education and moral reasoning to ethical practice: a meta
      analysis of quantitative studies.
AB  - This meta-analytic article of quantitative studies is aimed at summarizing
      knowledge gained on ethical practice for the period of 1987 to 1997 and at
      suggesting directions for future research. It specifically investigated the
      relationships of education and moral reasoning to ethical practice, with ethical
      practice as the dependent variable. The sample consisted of eight studies that
      investigated the relationship between education and ethical practice, and five
      studies that addressed the relationship between moral reasoning and ethical
      practice. A small to medium relationship between education and ethical practice
      was found, with an overall mean for effect sizes, d = .44, p = .000. To test the
      relationship between moral reasoning and ethical practice the Pearson product
      moment coefficient r was used as the effect size estimate, as each of the studies
      in this group reported correlation analyses. A small but significant relationship
      was found between moral reasoning and ethical practice (overall r of .2, p =
      .000). These results are evaluated in comparison to those of a decade earlier and
      overall trends are identified. As before, the majority of the studies are in the
      form of dissertations, and few of their authors have published their work in the
      general scientific literature. Similarly, clarity has not yet been achieved with
      regard to the conceptual and operational definitions of ethical practice.
      Theoretical, measurement, and policy issues are discussed in highlighting the
      implications of the study.

PMID- 11569301
TI  - Feminism and public health nursing: partners for health.
AB  - It is a well-known fact that nursing and feminism have enjoyed an uneasy
      alliance. In recent years, however, nursing has begun to recognize the importance
      of feminism. Nevertheless, the literature still rarely addresses the relevance of
      feminism for public health nursing. In this article, I articulate the relevance
      of feminism for public health nursing knowledge and practice. First, I define and
      describe feminism and public health nursing and then I discuss the importance of
      feminism for public health nursing practice. The importance of feminism for the
      metaparadigm concepts of public health nursing is then reviewed. Finally, I
      examine several existing challenges relating to feminism and public health
      nursing research, education, and practice. The thesis of this article is that
      feminism is vitally important for the development of public health nursing and
      for public health care.

PMID- 11569303
TI  - The 5th annual scientific meeting of the Japanese Heart Failure Society. October
      25-27, 2001. Sendai, Japan. Abstracts.

PMID- 11569304
TI  - Stats & facts. How do physicians use the Internet?

PMID- 11569302
TI  - Reflections on "recovery: a phenomenon extending beyond discharge".

PMID- 11569305
TI  - Managed care organizations publicly reporting three years of HEDIS measures.
AB  - The author compares the results of MCOs that have publicly reported their Health
      Plan Employer Data and Information Set (HEDIS) rates for 1997 through 1999 with
      health plans that did not report publicly. Managed care plans that publicly
      reported for three consecutive years performed better on preventive health
      measures than those that did not. Newer measures, such as beta-blocker treatment
      after a heart attack, showed the greatest improvement over time. Health care
      plans rated high in consumer experience also had higher clinical performance
      rates. Finally, plans that sought accreditation by the National Committee for
      Quality Assurance had better performance on their HEDIS measures, although the
      differences narrowed for those reporting HEDIS rates for three consecutive years.

PMID- 11569306
TI  - Linking exercise and outcomes: difficulties of study design.

PMID- 11569307
TI  - The effect of a fitness program on health status and health care consumption in
      Medicare MCOs.
AB  - This study examined the effect of a fitness program for Medicare MCOs on health
      status and health care utilization of participants. An evaluation compared
      outcome measures between high-level and low-level participants of the program.
      High-level participants scored higher on the Health Outcomes Survey and also had
      fewer doctor visits during the program period compared with low-level
      participants. The authors conclude that elderly individuals who participated at
      the high-level rate in a targeted fitness program maintained or improved health
      status and had fewer outpatient visits compared with the low-level participants.
      Medicare MCOs may improve health and manage costs for members by employing
      similar interventions focusing on functional health through exercise.

PMID- 11569308
TI  - Defined contribution plans do not change basic market distortions in U.S. health
      care.

PMID- 11569309
TI  - Meeting the challenges of a consumer-centric market in an era of new technology
      and new regulatory forces.
AB  - The emphasis on increased consumer choice, participation, and spending on health
      plans will result in more demands on an MCO's E-health capabilities. The author
      reveals the type of business plan that will be needed to cope with the
      information technology demands of a defined contribution future.

PMID- 11569310
TI  - Privacy rules under the Gramm-Leach-Bliley Act and HIPAA.
AB  - The intense scrutiny given to the privacy implications of the Gramm-Leach-Bliley
      Act and the Health Insurance Portability and Accountability Act has led to much
      confusion regarding which applies to specific entities. The authors attempt to
      clarify when these Acts would define how confidential medical data are used.

PMID- 11569313
TI  - Are you ready to build HIPAA's great wall of privacy?

PMID- 11569312
TI  - What are employers doing about prescription drug coverage for retirees?

PMID- 11569314
TI  - Taming wild drug costs.

PMID- 11569315
TI  - Cholesterol screening.

PMID- 11569316
TI  - Taming the time-off tiger.

PMID- 11569317
TI  - Productivity plus. The wellness principal.

PMID- 11569318
TI  - Antibody-based diagnostic and therapeutic innovations for human cancer.
AB  - As adjuvants, antibody-based diagnostic and therapeutic innovations can
      potentially decrease morbidity and mortality associated with many human
      malignancies. Current strategies employing genetically modified constructs may
      improve tumor penetration and increase versatility.

PMID- 11569319
TI  - Promoting informed decision making about prostate cancer screening.
AB  - Because prostate cancer screening with prostate specific antigen is
      controversial, informed consent is recommended. Physicians are encouraged to
      discuss facts about prostate specific antigen with patients and to supplement
      such discussions with informational brochures or videotapes.

PMID- 11569320
TI  - Cervical cancer screening from Pap smear to human papillomavirus DNA testing.
AB  - Human papillomavirus (HPV) types 16 and 18 are strongly associated with cervical
      cancer. Testing of HPV DNA in cervical specimens offers an useful option in
      triaging women with equivocal Pap smear diagnosis such as atypical squamous cells
      of undetermined significance.

PMID- 11569321
TI  - Controlling high blood pressure: a simple and effective approach.
AB  - Fixed-dose combination tablets, such as diuretic plus beta-adrenergic blocking
      drug or ACE inhibitor are more effective than is any monotherapy. Other
      advantages include simple titration, low toxicity and reduced expense which
      encourage better compliance required for optimal blood pressure control.

PMID- 11569322
TI  - Chronic idiopathic urticaria.
AB  - Chronic idiopathic urticaria is a disabling disease that affects many facets of
      life. Management requires knowledge of the etiology, as well as the treatment
      protocol. Physicians should also be aware of the overlap between chronic
      urticaria and idiopathic angioedema.

PMID- 11569323
TI  - The management of the red eye for the generalist.
AB  - Patients often present to primary care physicians with acute or chronic red eyes.
      Benign conditions may be evaluated and treated by primary care practitioners. Red
      eyes due to serious conditions may be vision threatening and require early
      detection and referral.

PMID- 11569324
TI  - Acute myocardial infarction 2000 treatment.
AB  - As the leading cause of death and a major cause of suffering and medical expense,
      modern management of acute myocardial infarction is essential. Although diagnosis
      and treatment have become complicated, recent improvements can be initiated by
      primary care physicians.

PMID- 11569325
TI  - Neurological manifestations of HIV-1 infection in the HAART era.
AB  - Neurologic complications in patients with AIDS are diverse and include
      opportunistic infections and lymphoma, as well as HIV-related peripheral
      neuropathy, myelopathy, and dementia. Improved prophylaxis and antiretroviral
      therapies have modified the approach to neurologic disease in the setting of
      AIDS.

PMID- 11569326
TI  - Approach to diagnosing lower extremity edema.
AB  - Edema, a sign of a localized or systemic disease process, results from a
      disruption in the normal physiological forces controlling extracellular fluid
      volume. This review utilizes an anatomical approach in discussing the various
      causes of edema.

PMID- 11569327
TI  - A risk management program based on full disclosure and trust: does everyone win?
AB  - When a patient is harmed by an error or negligence, hospitals tend to treat the
      patient as a threat. There is now theoretical and experiential evidence that full
      disclosure, apology and fair compensation may protect all parties at lower cost.

PMID- 11569328
TI  - Telemedicine for the Medicare population: pediatric, obstetric, and clinician
      indirect home interventions.
AB  - BACKGROUND: This report is a supplement to an earlier evidence report,
      Telemedicine for the Medicare Population, which was intended to help policymakers
      weigh the evidence relevant to coverage of telemedicine services under Medicare.
      That report focused on telemedicine programs and clinical settings that had been
      used with or were likely to be applied to Medicare beneficiaries. While we
      prepared that report, it became apparent that there are also telemedicine studies
      among non-Medicare beneficiaries--e.g., children and pregnant women--that could
      inform policymakers and provide more comprehensive evidence of the state of the
      science regarding telemedicine applications. In addition, the first evidence
      report only partially included a class of telemedicine applications (called self
      monitoring/testing telemedicine) in which the beneficiary used a home computer or
      modern-driven telephone system to either report information or access information
      and support from Internet resources and indirectly interact with a clinician.
      Self-monitoring/testing applications in the first report required direct
      interaction with a clinician. The goal of this report is to systematically review
      the evidence in the clinical areas of pediatric and obstetric telemedicine as
      well as home-based telemedicine where there is indirect involvement of the health
      care professional. (In this report, we will refer to the latter as clinician
      indirect home telemedicine.) Specifically, the report summarizes scientific
      evidence on the diagnostic accuracy, access, clinical outcomes, satisfaction, and
      cost-effectiveness of services provided by telemedicine technologies for these
      patient groups. It also identifies gaps in the evidence and makes recommendations
      for evaluating telemedicine services for these populations in the future. The
      evidence is clustered according to three categories of telemedicine service
      defined in our original report: store-and-forward, self-monitoring/testing, and
      clinician-interactive services. The three clinical practice areas reviewed in
      this report are defined as follows. The term pediatric applies to any
      telemedicine study in which the sample consisted wholly or partially of persons
      aged 18 or younger, including studies with neonatal samples. The term obstetric
      applies to any telemedicine study in which the sample consisted entirely of women
      seeking pregnancy-related care. The term clinician-indirect home telemedicine
      applies to home-based telemedicine (called self-monitoring/testing in our
      original report) where a telemedicine application used in the home has only
      indirect involvement by the health care professional. Interactive home
      telemedicine was applied in this report to all patient populations. KEY
      QUESTIONS: The key questions that served as a guide for reviewing the literature
      in the evaluation of pediatric, obstetric, and clinician-indirect home
      telemedicine applications were derived by consensus among the evidence-review
      team based on the analytic framework established for the original evidence
      report. For the current report, the questions were applied to studies in all
      three practice areas as a whole group within each of the three categories of
      telemedicine services: store-and-forward; self-monitoring/testing; and clinician
      interactive. The specific key questions were: 1. Does telemedicine result in
      comparable diagnosis and appropriateness of recommendations for management? 2.
      Does the availability of telemedicine provide comparable access to care? 3. Does
      telemedicine result in comparable health outcomes? 4. Does telemedicine result in
      comparable patient or clinician satisfaction with care? 5. Does telemedicine
      result in comparable costs of care and/or cost-effectiveness? METHODS: We
      searched for peer-reviewed literature using several bibliographic databases. In
      addition, we conducted hand searches of leading telemedicine journals and
      identified key papers from the reference lists of journal articles. For our
      original evidence report on telemedicine for the Medicare population, we designed
      a search to find any publications about telemedicine and used it to search the
      MEDLINE, CINAHL, and HealthSTAR databases for all years the databases were
      available. Through this process, we captured studies of pediatric, obstetric, and
      clinician-indirect home telemedicine; however, they were excluded from the
      original report since they were outside its scope. For this supplemental report,
      we reviewed our original search results and identified studies relevant to this
      report. We identified additional studies from the reference lists of included
      papers and from hand searching two peer-reviewed telemedicine publications, the
      Journal of Telemedicine and Telecare and Telemedicine Journal. We critically
      appraised the included studies for each study area and key question and discussed
      the strengths and limitations of the most important studies at weekly meetings of
      the research team. We also developed recommendations for research to address
      telemedicine knowledge gaps. To match these gaps with the capabilities of
      specific research methods, we classified the telemedicine services according to
      the type of evidence that would be needed to determine whether the specific goals
      of covering such services had been met. We emphasized the relationship between
      the type and level of evidence found in the systematic review of effectiveness
      and the types of studies that might be funded to address the gaps in knowledge in
      this growing field of research. FINDINGS: We identified a total of 28 eligible
      studies. In the new clinical areas, we found few studies in store-and-forward
      telemedicine. There is some evidence of comparable diagnosis and management
      decisions made using store-and-forward telemedicine from the areas of pediatric
      dental screening, pediatric ophthalmology, and neonatalogy. In self
      monitoring/testing telemedicine for the areas of pediatrics, obstetrics, and
      clinician-indirect home telemedicine, there is evidence that access to care can
      be improved when patients and families have the opportunity to receive telehealth
      care at home rather than in-person care in a clinic or hospital. Access is
      particularly enhanced when the telehealth system enables timely communication
      between patients or families and care providers that allows self-management and
      necessary adjustments that may prevent hospitalization. There is some evidence
      that this form of telemedicine improves health outcomes, but the study sample
      sizes are usually small, and even when they are not, the treatment effects are
      small. There is also some evidence for the efficacy of clinician-interactive
      telemedicine, but the studies do not clearly define which technologies provide
      benefit or cost-efficiency. Some promising areas for diagnosis include emergency
      medicine, psychiatry, and cardiology. Most of the studies measuring access to
      care provide evidence that it is improved. Although none of these studies were
      randomized controlled trials, they provide some evidence of access improvement
      over prior conditions. Clinician-interactive telemedicine was the only area for
      which any cost studies were found. The three cost studies did not adequately
      demonstrate that telemedicine reduces costs of care (except comparing only
      selected costs). No study addressed cost-effectiveness. CONCLUSIONS: This
      supplemental report covering the areas of pediatrics, obstetrics, and indirect
      clinician home telemedicine echoes the findings of our initial report for the
      Medicare domain, which is that while the use of telemedicine is small but
      growing, the evidence for its efficacy is incomplete. Many of the studies are
      small and/or methodologically limited, so it cannot be determined whether
      telemedicine is efficacious. Future studies should focus on the use of
      telemedicine in conditions where burden of illness and/or barriers to access for
      care are significant. Use of recent innovations in the design of randomized
      controlled trials for emerging technologies would lead to higher quality studies.
      Journals publishing telemedicine evaluation studies must set high standards for
      methodologic quality so that evidence reports need not rely on studies with
      marginal methodologies.

PMID- 11569329
TI  - The myth of low-fat diets.

PMID- 11569330
TI  - Psychosocial predictors of postpartum depression in diverse groups of women.
AB  - The purpose of this study was to test the extent to which a causal model
      developed from a theoretical formulation of postpartum depression was consistent
      with data collected from three groups of postpartum women. In this cross
      sectional, correlational design, the samples consisted of primarily middle-class,
      Caucasian mothers of term infants and preterm infants, and low-income, African
      American mothers of term infants. Instruments included the CES-D Depression
      instrument, the Postpartum Support Questionnaire, Rosenberg's Self-Esteem
      instrument, and a question regarding closeness to partner. The causal model was
      tested with structural equation modeling. Importance of support, support
      received, and closeness to partner were significant predictors of both self
      esteem and depression. Predictors of postpartum depression are the same across
      diverse samples of women, as proposed in the causal model.

PMID- 11569331
TI  - Participation of immigrant women family caregivers in qualitative research.
AB  - The recruitment of articulate, expressive participants is an essential part of
      methodology in qualitative research. This article presents the authors'
      experience in the recruitment of immigrant women of Chinese and South Asian
      origin in an ethnographic study. The study included women caring for an adult or
      child family member who had a chronic health problem. Knowledge of women family
      caregivers' health is restricted by the failure to include diverse groups of
      women in research. In this article, the authors discuss issues related to
      recruitment and participation of immigrant women in research, including
      establishing access to diverse groups of women, benefits for immigrant women, and
      placing the researcher and research process on the same level. Practical research
      strategies to address these issues and engage the women in research that portrays
      their perspectives are presented. The authors' discussion concludes with
      reflection on their experience and that of other researchers.

PMID- 11569332
TI  - Isolation in blood and marrow transplantation.
AB  - This phenomenological study explored the perceptions of 20 patients who had
      undergone an autologous bone marrow transplantation (ABMT). Transcripts from
      interviews were analyzed for themes. Three themes emerged related to the
      experience of isolation during and after ABMT: physical isolation (protecting
      self and others), emotional isolation (protecting self and others), and physical
      and emotional isolation (supporting self and others). During physical isolation,
      participants were protected from infection and tried to protect family and
      friends from emotional burden. However, physical isolation often led to emotional
      isolation, which the physical presence of others ameliorated, particularly when
      an emotional presence was coexistent. Emotional presence was a main source of
      social support. Participants felt family and friends needed more guidance on ways
      to provide effective support. An important implication for health care
      professionals is that emotional support in the form of positive presencing should
      accompany providing information to both patients and family members.

PMID- 11569333
TI  - Testing a predictive model of what makes a critical thinker.
AB  - The goal of nursing education is to help individuals become self-determining,
      independent thinkers. Cognitive development may be the outcome that best
      characterizes such a thinker. The purpose of this study was to test a model of
      cognitive development in which four independent variables--knowledge base,
      critical thinking skills, critical thinking dispositions, and experience--were
      used to predict cognitive development. Data were analyzed from 232 practicing
      registered nurses. Three hierarchical levels of cognitive development were
      examined: dualism, relativism, and commitment. Critical thinking skill was a
      significant contributor only to the dualistic level of cognitive development.
      Critical thinking dispositions contributed to all three levels of cognitive
      development. Experience contributed only to the commitment level. The results of
      this study suggest that the development of a critical thinker may require time
      and experience. These findings can be used to examine current policy regarding
      the criteria used to evaluate nursing education.

PMID- 11569334
TI  - Use of videotaped interventions in research.
AB  - Evaluating conceptual and methodological issues are important considerations when
      developing a videotape for research intervention. The process of developing a
      videotape for research involves several critical steps to maintain scientific
      rigor during the project. Establishing content validity of the videotape script
      and maintaining scientific integrity while producing the videotape are key
      components. Issues such as copyright and intellectual property are important
      considerations. The use of videotape provides a consistent method of providing
      information to research subjects. Careful attention to the research process
      during each phase of development of the videotape will enhance the success of the
      project.

PMID- 11569335
TI  - Mary Breckinridge--a voice from the past.

PMID- 11569336
TI  - [Means for volumetric fire extinguishing in inhabited facilities].
AB  - The authors discuss the problem concerning the substitution of ozone-destroying
      fire extinguishing halogen hydrocarbons 13B1, 12B1 and 114B2 with alternative
      means of volumetric fire extinguishing. The toxicological-and-hygienic
      characteristics of chladon 13B1 and of the new ozone-harmless extinguishers
      (chladons 124B1 and 125, sulphur hexafluoride and aerosol-forming means of
      volumetric fire extinguishing) are shown.

PMID- 11569337
TI  - [Diagnosis and prevention of the military suicidal behavior (Part 1)].

PMID- 11569338
TI  - [Inherited alcoholism aggravation].

PMID- 11569339
TI  - [Nutritional support for wounded and traumatized: state of the problem].

PMID- 11569340
TI  - [Questionnaire method of examination of patients with vertebrogenic lumbar
      ischialgia].

PMID- 11569341
TI  - [Optimization of early diagnosis of infectious endocarditis].

PMID- 11569342
TI  - [Conduction of tactical and special training with the military clinical hospital
      of the North-Caucasian Military District].

PMID- 11569343
TI  - [Neurological complications as a debut of infectious endocarditis].

PMID- 11569344
TI  - [Delayed effects of low doses of ionizing irradiation on higher psychic
      functions].

PMID- 11569345
TI  - [Modern local therapy of foot mycoses in servicemen].

PMID- 11569346
TI  - [Sermion in the treatment of patients with neurological diseases].

PMID- 11569347
TI  - [Ultrasonic differential diagnosis of small echo-positive formations in kidneys].

PMID- 11569348
TI  - [Pneumonia epidemiology and prophylaxis in servicemen in local wars and military
      conflicts].
AB  - The high military-and-epidemiological significance of pneumonia in servicemen
      during the war in Afghanistan (1979-1989) and the armed conflict in Chechnia
      (1995-1996) is shown and the measures for increasing the pneumonia incidence in
      the regions of operations are substantiated. It is established that more than 70%
      of pneumonia are conditioned by pneumococci that rather frequently show the
      pathogenic features against the background of viral (usually influenzal)
      respiratory infection or in association with Hemophilic bacillus, Chlamydia or
      Mycoplasma. The main factor leading to development of pneumonia during the period
      of local wars is the decreased organism resistance caused by supercooling,
      stresses and overwork as well as untreated acute respiratory diseases.

PMID- 11569349
TI  - [Vaccine prophylaxis of viral hepatitis A in epidemic areas].

PMID- 11569350
TI  - [Comparison of professional qualities of military physicians in various
      conditions].

PMID- 11569351
TI  - [Etiological factors, clinical and diagnostical characteristics of
      neurocirculatory dystonia in military pilots].

PMID- 11569353
TI  - [Organization of medical and evacuation measures for burned during war in
      Afghanistan].

PMID- 11569354
TI  - [75 Years of Dushanbe military hospital].

PMID- 11569355
TI  - [60 Years of Volgograd military district hospital].

PMID- 11569356
TI  - [On the 60th year of graduation of doctor's assistants from Krondshtadt Navy
      medical school].

PMID- 11569357
TI  - The use of the carbon-fiber reinforced modular implant for the reconstruction of
      the anterior column of the spine. A clinical and experimental study conducted on
      42 cases.
AB  - The conservative treatment of neoplasms of the locomotor apparatus means the
      production of bone defects that may be filled with prostheses, bone grafts,
      systems of osteosynthesis. In the vertebral column, reconstruction of the
      resected elements--in the case of total vertebrectomy--requires the combination
      of anterior and posterior implants. It is the purpose of this study to analyze a
      group of 42 patients who, after accurate and uniform oncological (Enneking) and
      surgical (Weinstein-Boriani-Biagini) staging, were submitted to excision of one
      or more vertebral bodies for the treatment of neoplastic pathology, with
      reconstruction by prosthetic carbon fiber modular implant in order to obtain
      immediate stability, and to stimulate solid intervertebral fusion by bone grafts
      introduced inside the prosthesis. Thirty of the 42 patients presented with
      primary malignant tumor, 3 with benign tumor, 6 with solitary metastases, and 3
      with plasmacytoma. In 32 cases, en bloc resection of the vertebral body was
      carried out (vertebrectomy) with combined anterior and posterior access in 29
      patients (69.0%), and by posterior approach alone in 3 cases (7.1%). Ten
      intralesional corporectomies were carried out, 8 by anterior approach, 2 by
      posterior approach. The carbon prosthesis was filled with cortical and cancellous
      bone grafts in 38 cases. At a mean clinical and instrumental follow-up obtained
      26 months after surgery for all of the patients, the use of a carbon prosthesis
      did not cause short- or long-term mechanical complications. The results of our
      study tend to affirm that the use of a carbon fiber modular implant may fill any
      loss of bone substance of the vertebral column, that it allows for immediate
      weight-bearing, and that if favors bone fusion. Some particular features of the
      carbon prosthesis favorably adapt to the surgical method of vertebrectomy: 1. The
      various components of the prosthesis may adapt to any type of bone resection of
      the vertebral body, even in unexpected situations; 2. Connection to posterior
      instrumentation in total vertebrectomies avoids the use of an anterior plate,
      thus reducing the time required for reconstruction of the anterior column,
      eliminating necessary surgical procedures in the segmental vascular structures.
      Finally, the radiolucency of the prosthesis allows for an easy evaluation of the
      formation of bone within and around the implant up to definitive anterior fusion
      and, of no less importance, early diagnosis of any local recurrence.

PMID- 11569358
TI  - Microdiscectomy in the treatment of lumbar disc herniation.
AB  - The authors report their experience with short- and medium-term microdiskectomy
      for the treatment of lumbar disc herniation. It is based on 760 operations
      performed between 1985 and July 1999: expulsed hernias and those of large size
      with intense pain symptoms and/or neurologic deficit were treated. During the
      same period of time, the authors used enzymatic and percutaneous nucleolysis
      according to Onik for smaller hernias. The incidence of satisfactory results was
      high (90.1%), in agreement with the results published in the literature. There
      was a low incidence of complications (4.6%), and of these 2.8% had a benign
      spontaneous evolution; 1% was prevented during surgery, 0.5% was prevented with
      subsequent surgery, while only 0.2% was the cause of definitive failure.
      Unsatisfactory results were constituted by the sequelae of complications (1
      discitis, 4 liquoral cysts, 1 error in level not diagnosed intraoperatively),
      stenosis of the lateral recess not diagnosed pre- or intraoperatively, and thus
      not treated; in 6.1% of cases there was no plausible justification. The
      microsurgical technique above all reduces the duration of hospitalization (5 days
      on the average, but with 91% of cases dismissed on day 3), and allows for a rapid
      return to work activity (after 63 days for patients who are not employees, but
      with a return after 20 days in 95% of cases).

PMID- 11569359
TI  - Posterior lumbar interbody fusion a mid-term review of 60 cases.
AB  - It is the purpose of this study to evaluate the clinical and radiographic medium
      term results of a series of 60 patients submitted to intersomatic lumbar fusion
      by posterior approach, using a system constituted by carbon wedges to be
      associated with bone grafts for intersomatic fusion, and by steel or titanium
      plates or bars used for posterior pedicle osteosynthesis. Satisfactory clinical
      results were obtained in 88.2% of cases and complete radiographic fusion in 91.4%
      of cases. Complications were generally observed in 8.3% of cases. In light of
      these results, we may consider intersomatic lumbar fusion by posterior approach a
      method that is perhaps aggressive, but effective in the treatment of severe
      lumbar spondylolysis. The use of carbon wedges brings several advantages that
      favor intersomatic fusion, its progressive control, and the restoration of normal
      lordosis of the lumbar spine.

PMID- 11569360
TI  - Dislocation of the proximal femoral epiphysis in acetabular fractures.
AB  - Acetabular fractures are often associated with dislocation of the proximal
      femoral epiphysis. The dislocation may be of three types, based on the type of
      fracture to which it is associated: anterior, central, posterior. In anterior and
      in central dislocation epiphyseal necrosis of the proximal femur has never been
      observed, while in posterior dislocation necrosis has been observed in 23% of
      cases. Diagnosis of posterior dislocation is of essential importance so that it
      may be reduced immediately, decreasing the risk of necrosis. The authors report a
      review of 192 fractures of the acetabulum to which dislocation of the femoral
      epiphysis was associated, treated between 1980 and 1996 at the IIIrd Division of
      the Rizzoli Orthopaedic Institute.

PMID- 11569361
TI  - The surgical treatment of fractures of the proximal end of the tibia: a review of
      cases as related to prognostic factors.
AB  - It is the purpose of this retrospective study to analyze factors capable of
      influencing clinical-functional and radiographic results, such as type of
      fracture, age of the patients, type of trauma, delay in treatment, associated
      lesions. A total of 33 fractures treated by open reduction and internal
      stabilization for fractures of the proximal tibia classified according to the AO
      were re-evaluated. Clinical and radiographic evaluation were obtained by
      assessing arthrosis, axis, and sinking of the tibial plateau. The clinical and
      functional results were satisfactory in 72.2% of cases, and radiographic ones
      were satisfactory in 63.6% for gonarthrosis, in 81.6% for axis, and in 84.8% for
      sinking. In conclusion, factors capable of influencing the results, such as type
      of fracture, age of the patient, and type of trauma, in addition to variables
      that the surgeon must monitor, such as reconstruction of the joint, alignment,
      synthesis, treatment of meniscal lesions, were observed.

PMID- 11569362
TI  - The treatment of post-traumatic stiffness of the elbow.
AB  - The authors present the results observed in 12 patients affected with post
      traumatic stiffness of the elbow treated by an external fixator in distraction to
      obtain functional recovery of range of movement; in all of the cases anterior and
      posterior release and resection of the apex of the olecranon was carried out,
      while in 2 cases interposition arthroplasty with freeze-dried dura madre was
      associated. The series includes 12 cases with a long-term follow-up that ranges
      from 8 to 33 months after surgery. The mean arch of movement during the
      preoperative phase was 35 degrees (minimum 0 degree-maximum 90 degrees) in
      flexion extension and 80 degrees (minimum 0 degree-maximum 150 degrees) in
      pronosupination. Recovery of mean joint excursion in flexion-extension was 91
      degrees and in pronosupination it was 127 degrees. Complications included
      loosening of the nails in 2 cases, breakage of the nails in 1 case, and
      transitory deficit of the ulnar nerve in 4 cases. A total of 11 patients (91.66%)
      declared that they were satisfied with the considerable improvement in their
      ability to do daily activities. The results of arthroplasty in distraction in the
      elbow are satisfactory even if much attention must be paid to the selection of
      the patients because of the intense collaboration that is required during
      postoperative rehabilitation.

PMID- 11569363
TI  - Surgery in massive ruptures of the rotator cuff: results as related to prognosis.
AB  - The results obtained in the surgical treatment of massive lesions of the rotator
      cuff are quite often inferior to what is expected, because prognosis is not
      respected. To demonstrate that the quality of the results obtained is directly
      proportional to the preoperative prognostic factors a retrospective study was
      conducted on 28 patients submitted to massive lesion repair of the rotator cuff
      between 1990 and 1996; the criteria of inclusion was: a) patients aged under 65
      years; b) preoperative radiographic findings with acromiohumeral distance not
      less than 6 mm; c) degeneration of the tendons not greater than a Goutallier
      stage 2; d) absence of inveterate pseudoparalysis of the limb involved; e)
      absence of anterosuperior subdislocation of the humeral head. The results
      obtained with a mean follow-up of 5 years revealed a mean Constant score of 85
      points (minimum 79, maximum 91) that may correspond to excellent results, showing
      how this type of surgery may guarantee good results only when factors of
      prognosis are respected preoperatively.

PMID- 11569364
TI  - Core decompression in the treatment of necrosis of the femoral head. Long-term
      results.
AB  - Long-term follow-up (5 years and 7 months) was obtained for the results of core
      decompression in 18 patients (20 hips) affected with ischemic necrosis of the
      femoral head at Ficat stages I and IIA. Two methods were used to diagnose
      osteonecrosis: bone scan, and MRI. Progression of the disease was monitored by
      annual MRI. The persistence of pain, progression of the disease in the Ficat
      scale, the use of total arthroplasty, were considered to be signs of failure.
      Core decompression was favorable in 16 hips, there was progression of the disease
      in 4. Good results were observed in 90% of the stage I necroses and in 70 of the
      stage IIA necroses. The results of the present study suggest bone reaming as the
      treatment of choice in initial stages of necrosis. Thus, the need for
      arthroplasty in young patients is delayed.

PMID- 11569365
TI  - Experimental study on the cement mantle in hip arthroplasty: effect of defects on
      the property of the materials used.
AB  - The study simulated implantation of a hip prosthesis stem in the femur. The
      cement mantle produced in vitro was observed under an optic microscope. A higher
      concentration of porosity in the cement mantle at the stem-cement interface was
      observed. By heating the stem to 45 degrees C and 55 degrees C the authors
      observed a reduction in porosity in the three surfaces examined: stem-cement
      interface, internal surface, and cement-pseudofemur interface. Heating of the
      stem causes a reduction in polymerization time and an increase in maximum
      temperature achieved during the polymerization process. A reduction in porosity
      at the stem-cement interface influenced bending strength of the specimens
      extracted from the mantle. A significant difference between resistance to flexion
      in the specimens produced with the stem at 55 degrees, and in those with the stem
      at 23 degrees C was observed.

PMID- 11569366
TI  - Epiphysiolysis of the hip: relationship between etiopathogenesis and hormone
      status.
AB  - The authors present a review of the literature on the etiology of epiphysiolysis
      of the hip and an original study on the hormone status of these patients. By
      examining eleven values including hormones, vector proteins, and hormonal
      transport, the authors related the data obtained to the anagraphical age of the
      patient, to his or her skeletal age, to the development of sexual features, and
      to the radiologic evidence of pathology. In light of the results obtained,
      despite the fact that the study only included 23 patients, the modified
      equilibrium between SHBG and Somatomedin C, would seem to lead to an accelerated
      turnover in the growth plate. The increase in BMI directly correlated with low
      levels of SHBG is also an indication of the increase in body weight that
      certainly contributes to slippage of the femoral head.

PMID- 11569367
TI  - Airport metal detectors and orthopaedic implants.
AB  - A total of 18 subjects with a variety of orthopaedic implants and volunteers with
      the same but exteriorly fixed implants were examined by security staff of an
      airport using arch and hand-held detectors. All the implants activated the metal
      arch detectors but a small number of these activated the alarm threshold. The
      hand-held detectors alarmed overall superficial implants. For all these reasons
      it is therefore imperative that each patient carry a suitable certificate in
      order to avoid searching.

PMID- 11569368
TI  - [Customary use of compression stockings for prevention of thrombosis in medical
      intensive care units in Germany].
AB  - BACKGROUND: Stockings for thrombosis prophylaxis (MTS) are generally advised for
      all immobilized patients by the German Societies of Surgery, Orthopedics, and
      Phlebology. In critical care patients, the indication is unclear and many
      questions are left unanswered, especially if combined with heparins for
      prophylaxis of thromboembolism. We evaluated the customary use of MTS in critical
      care patients. METHODS: A multiple choice questionnaire was sent to the nursing
      staff of 324 randomly selected German non-surgical ICUs. The answers of 144 units
      (44.4%) could be evaluated, 15 of which were special neurology, 88 special
      internal medicine, 41 mixed. RESULTS: Each 8th ICU principally avoids MTS, each
      19th ICU principally provides all patients with MTS. Of those who use special
      indications, the degree of immobilisation plays an indecisive role with 50% for
      and 50% against MTS. In particular, coma serves as a contraindication. Effective
      anticoagulation excludes the need for MTS in half of the ICUs. Polyneuropathies
      and dysesthesias are the far most noticed arguments against MTS. CONCLUSIONS:
      There seems to be an uncertainty about the indication of MTS for non-surgical
      critical ill patients. With respect to available guidelines, a decision in
      principle for MTS should be made. However, in the individual patient with
      relative contraindications and progressively effective anticoagulation, MTS may
      be dispended relatively liberally.

PMID- 11569369
TI  - [Cold agglutinins of the IgM class in a patient with monoclonal gammopathy of the
      IgA class].
AB  - HISTORY AND CLINICAL PRESENTATION: A 61-year-old patient was examined in hospital
      because he had suffered from fatigue and weight loss for several years. History
      and physical examination showed no symptoms specific for a disease of a
      particular organ except a goitre. INVESTIGATIONS: Laboratory examination serum
      showed a decreased haptoglobin, a slightly elevated bilirubin, an acceleration of
      the blood sedimentation rate and a M-gradient in the protein electrophoresis. The
      immunofixation electrophoresis revealed a monoclonal gammopathy of the IgA-class.
      The cold agglutinin titre was clearly elevated (2048 at 4 degrees C), caused by
      an auto-anti-I of the IgM-class. No signs of an infection or a haematological
      neoplasm were found. TREATMENT AND COURSE: No specific therapy was given for the
      compensated haemolytic anaemia and the monoclonal gammopathy. There was no
      significant change in the course of the disease over 5 years. CONCLUSION: Between
      the specificity and the immunoglobulin class of cold agglutinins correlations
      exist that are also of significance for these autoantibodies. As shown by this
      case, an exact analysis of the specificity and the immunoglobulin class of cold
      agglutinins should be done in cases with unusual combinations of laboratory
      results to prevent misleading interpretations.

PMID- 11569370
TI  - [Spontaneous intraspinal epidural hematoma secondary to use of platelet
      aggregation inhibitors].
AB  - HISTORY AND ADMISSION FINDINGS: A 64-year-old woman previously in good health
      experienced an acute onset of severe neck pain and weakness of the left arm that
      had developed within minutes. Neurological examination revealed paresis of the
      left arm. There was a previous history of cardiovascular disease and she had been
      treated with 100 mg of aspirin per day. INVESTIGATIONS: MRI revealed a left
      posterolateral intraspinal mass extending from C3 to C7. The hemostatic
      evaluation showed no abnormalities (platelet count, prothrombin time, partial
      thromboplastin time). TREATMENT AND COURSE: A laminectomy with evacuation of the
      epidural hematoma was performed. The postoperative course was uneventful, with
      complete disappearance of the neurological deficit. CONCLUSION: We report a rare
      condition of spontaneous spinal epidural hematoma that was associated with
      aspirin intake. A short time interval from onset of symptoms to diagnosis (MRI)
      and surgery is crucial for the outcome.

PMID- 11569371
TI  - [Gallstones--diagnosis].

PMID- 11569372
TI  - [Gallstones--therapy].

PMID- 11569373
TI  - [Preimplantation diagnosis as controversy. Which ethical arguments are helpful
      and which are not?].

PMID- 11569374
TI  - [Should the label be explained to the patient by the physician?].

PMID- 11569375
TI  - [Abortion in forced labor camps in the Third Reich. The opinion of the
      contemporary clinical director H. Eymer].

PMID- 11569376
TI  - [Results of a "silly" mistake: legionnaires' disease].

PMID- 11569377
TI  - Memorandum, the surgeon general to the adjutant general May 23, 1900.

PMID- 11569378
TI  - Biography of Walter Reed.

PMID- 11569379
TI  - Biography of James Carroll.

PMID- 11569380
TI  - Biography of Aristides Agramonte.

PMID- 11569382
TI  - Memorandum: Henry R. Carter to Jesse Lazear, undated.

PMID- 11569383
TI  - Letter: Walter Reed to James Carroll, September 7, 1900.

PMID- 11569384
TI  - The etiology of yellow fever-- a preliminary note. 1900.

PMID- 11569385
TI  - Introduction: yellow fever before 1900.

PMID- 11569386
TI  - Contract between Antonio Benigno and Yellow Fever Board, November 26, 1900 .

PMID- 11569387
TI  - Letter: Walter Reed to Albert E. Truby, December 10, 1900 .

PMID- 11569388
TI  - General Orders No. 6: Headquarters Department of Cuba, Havana, December 21, 1900
      .

PMID- 11569389
TI  - Letter: Walter Reed to Emilie Reed, December 31, 1900    .

PMID- 11569390
TI  - The etiology of yellow fever: an additional note . 1901.

PMID- 11569391
TI  - The mosquito hypothetically considered as the agent of transmission of yellow
      fever. 1881.

PMID- 11569392
TI  - Letter: Walter Reed to Henry R. Carter, February 26, 1901 .

PMID- 11569393
TI  - Experimental yellow fever. 1901.

PMID- 11569394
TI  - Cable: James Carroll to The Surgeon General, October 22, 1901.

PMID- 11569395
TI  - The etiology of yellow fever: a supplemental note. 1902.

PMID- 11569396
TI  - The Detachment Hospital Corps, Columbia Barracks, Cuba 1900.

PMID- 11569397
TI  - The inside history of a great medical discovery. 1915.

PMID- 11569398
TI  - Epilogue: the U.S. Army Yellow Fever Board of 1900.

PMID- 11569399
TI  - Genetics of human type 1 diabetes mellitus.

PMID- 11569400
TI  - Defects in deletional tolerance of CD8+ T cells in autoimmune diabetes.

PMID- 11569401
TI  - How beta cells die in type 1 diabetes.

PMID- 11569402
TI  - Interactions of effectors and regulators are decisive in the manifestations of
      type 1 diabetes in nonobese diabetic mice.

PMID- 11569403
TI  - Cytokine regulation of diabetes in experimental models.

PMID- 11569404
TI  - Understanding the interaction of genetics and cellular responses in nonobese
      diabetic mice.

PMID- 11569405
TI  - Human T-cell responses to islet cell antigens.

PMID- 11569406
TI  - Autoantibodies in human diabetes.

PMID- 11569407
TI  - Transplantation tolerance.

PMID- 11569408
TI  - Role of regulatory T cells in the pathogenesis of autoimmune diabetes.

PMID- 11569409
TI  - Genes and cellular requirements for autoimmune diabetes susceptibility in
      nonobese diabetic mice.

PMID- 11569410
TI  - Immunotherapy of type 1 diabetes mellitus.

PMID- 11569411
TI  - The mucosal interface between 'self' and 'non-self' determines the impact of
      environment on autoimmune diabetes.

PMID- 11569413
TI  - [Original work in the Ceska gynekologie journal].

PMID- 11569412
TI  - Is activation of autoreactive lymphocytes always detrimental? Viral infections
      and regulatory circuits in autoimmunity.

PMID- 11569414
TI  - [Hormonal contraception and thromboembolic disease--new epidemiologic data].
AB  - OBJECTIVE: To sum up the results of studies published between 1996 and 2000 on
      the venous thromboembolism (VTE) risk at combined oral contraceptives users.
      DESIGN: Review of literature. SETTING: 1st Department of Obstetrics and
      Gynecology, Masaryk University, Brno, Czech Republic. METHODS: Summary of the
      results of substantial studies published on this topic. Studies were identified
      by Medline database search. RESULTS: Four important epidemiological studies
      published at 1995 and 1996 (WHO, Spitzer et al., Jick et al., Bloemenkamp et al.)
      demonstrated two fold increased risk of VTE at users of third generation OCs in
      comparison with second generation OCs. Publication of these studies was followed
      by critic based on their possible methodological weaknesses (prescribing bias,
      "healthy user" effect, refferal bias etc.). Other epidemiologists confirmed
      results of these studies and excluded the possibility of systematic biases.
      Pathophysiological mechanisms that could explain the different risks were also
      found. Jick's analysis of GRPD published in 2000 also confirmed the results from
      1995 and 1996. CONCLUSION: The different risk of VTE at users of oral
      contraceptives with different progestins probably exists. However, the relative
      risks of VTE demonstrated in recent studies are low.

PMID- 11569415
TI  - [Regression of hCG in various types of molar pregnancies--clinical course and
      prognosis].
AB  - OBJECTIVE: To evaluate spontaneous regression curves of hCG serum positivity in
      patients with surgically treated molar pregnancies. Comparison of complete,
      partial and invasive mole. The study should result in optimalisation of follow up
      criteria of molar pregnancies in respect to their potential malignant change.
      DESIGN: Retrospective comparative clinical study. SETTING: Obst. Gyn. Dpt.,
      Oncogynecology div., 2nd Medical Faculty, FNM, Charles University Prague,
      Pathology Dpt., 2nd Medical Faculty, Institute of Biology and Medical Genetics.
      METHODS: Evaluation of spontaneous regression curves of serum hCG levels in 104
      molar pregnancies. 46 patients with partial hydatiform mole, 48 patients with
      complete hydatiform mole, 10 patients with invasive mole. Serum hCG levels were
      detected by radioimunoassay (RIA) in the first period and imunochemoluminisent
      assay (LIA) in the second period. Regression curves of hCG positivity in
      particular moles were statistically evaluated by Fischer test and t-test.
      RESULTS: There is statistically significant difference in spontaneous regression
      of hCG positivity in different types of molar pregnancies. Recommended criteria
      for gestational trofoblastic disease (GTD) diagnosis and follow up are fully
      applicable in clinical practice. There is exception in partial hydatiform moles,
      where plateau in hCG regression does not necessarily implicate chemotherapy in
      patient with good compliance. CONCLUSION: Early diagnosis of GTD predominantly
      due to the widespread use of ultrasonography changes classical clinical features
      of molar pregnancies. Spontaneous regression in hCG positivity in serum is more
      rapid in patients with partial hydatiform mole, slower in complete hydatiform
      mole and invasive mole. There is no significant change in malignant potential
      regarding early detection and treatment.

PMID- 11569416
TI  - [Changes in lipid profiles in women after surgical castration during the fertile
      age].
AB  - OBJECTIVE: The main known risk factors for coronary heart disease in women, other
      than age, which is the most important risk factor of all, are cigarette smoking,
      raised blood pressure, obesity, diabetes and premature menopause, especially
      after ovarectomy. DESIGN: Retrospective clinical study. SETTING: Medical
      building, Prague 7, Department of Obstetrics and Gynecology 3rd Medical Faculty
      Charles University and Faculty Hospital Vinohrady, Prague 10. METHODS: In 1995
      and 1996 we investigated plasma lipid levels and bone density in 75 women, 3 to 5
      years after ovarectomy without HRT (group A). The results were compared with a
      control group (group B) of women of the same age and BMI. This group of women had
      normal menstruation periods. We investigated age, body mass index, bone density,
      total cholesterol, HDL and LDL cholesterol, ateroghenic index and triglycerides.
      RESULTS: When we compared groups A and B, there was a better result in all serum
      lipid levels in group B, but not significantly. In group A was more women with
      patological level of HDL-cholesterol. In group A there was a significantly lower
      level of bone density than in group B and there was an increase in the number of
      patients with osteoporosis in this group. CONCLUSIONS: Castration in premenopause
      had no influence in mean levels of parameters of lipid metabolism, but bone
      density significantly decreased after castration in this period.

PMID- 11569417
TI  - [Endometrial ablation and resection techniques].
AB  - OBJECTIVE: To summarize all currently used and experimental, hysteroscopic and
      non-hysteroscopic methods of endometrial ablation and resection, their
      indications, operation techniques, and treatment results. DESIGN: Literary
      review. SETTING: Department of Obstetrics and Gynecology, Medical Faculty and
      Faculty Hospital, Charles university, Capkovo namesti 1, Plzen, Czech Republic.
      METHODS: Analysis of the literature (textbooks, medical journals, database
      Medline, Current Contents, Embase, PubMed). RESULTS AND CONCLUSION: Endometrial
      ablation and resection play an important role in the treatment of dysfunctional
      uterine bleeding. Hysteroscopic methods visualize the uterine cavity and enable
      to treat lesions in it at the same time. Non-hysteroscopic methods are less
      invasive for the patient and comfortable for the surgeon. Both groups of methods
      have similar treatment results.

PMID- 11569418
TI  - [Laparoscopic-assisted myomectomy--surgical technique and indications].
AB  - OBJECTIVE: To analyze perioperative outcomes of laparoscopically assisted
      myomectomy. DESIGN: Pilot study. SETTING: Department of Obstetrics and
      Gynaecology, Endoscopic Training Centre, Hospital Kladno, Czech Republic.
      MATERIAL AND METHODS: Eight consecutive women with fibromyoma were treated by
      laparoscopic assisted myomectomy. Laparoscopic surgery was performed based on
      size of fibromyoma over 6 cm. RESULTS: The application of the operative technique
      of laparoscopically assisted myomectomy was effective in all out exception. In
      the studied group the mean operative time and the mean of weight of the specimen
      were 76 min (range 50-90) and 151.7 g (range 45-220), respectively. In one
      patient the relaparoscopy for bleeding was necessary. CONCLUSION: Laparoscopic
      assisted surgery is feasible in women with fibromyoma and may also be considered
      for myomectomy.

PMID- 11569419
TI  - [Laparoscopic neovaginoplasty--a modification of the Vecchietti operation].
AB  - OBJECTIVE: To asses laparoscopic approach to neovaginoplasty. DESIGN:
      Retrospective clinical study. SETTING: Department of Gynecology and Obstetrics,
      2nd Medical Faculty of Charles University. METHODS: Vecchietti's neovaginoplasty
      is considered to be the most advantageous technique of creating neovagina in
      vaginal agenesis, because of low perioperational morbidity and quicker recovery.
      Authors describe own modification of laparoscopic procedure based on designed
      equipment of themselves. RESULTS: Study evaluates 17 cases of laparoscopic
      procedures, which are compared with classical laparotomic approach we were
      experienced in past. Time of surgery was shorter (48 min vs. 66 min) and blood
      loss was lower (15 ml vs. 50-100 ml) in laparoscopic procedure. Number of
      complications was lower in this procedure too. There was no difference in length
      of hospital stay and size of neovagina. CONCLUSION: Laparoscopic modification is
      safe procedure and comparable with classic operation as regards surgical effect.
      Both types of procedures are determined for workplaces with experience in special
      reconstructive surgery and follow-up.

PMID- 11569420
TI  - [Ovarian implantation of the embryo in IVF and ET--early mole with proliferative
      trophoblast].
AB  - OBJECTIVE: Case report of a very rare case of ovarian implantation after IVF and
      ET treated by laparoscopy. DESIGN: Case report. SETTING: Institute for the Care
      of Mother and Child, Prenatal Diagnostic Centre and Trophoblastic Disease Centre,
      Prague, Institute for Postgraduate Medical Education, Prague. RESULTS: We
      observed implanted product of conception found within the ovarian stroma 35 days
      after ET. At laparoscopy, the genital sac appeared as an inconspicious
      haemorrhagic cyst, 2 cm in diameter. After dissection, in the intact sac appeared
      amorphous 2 mm embryo and 3 mm yolk sac. The trophoblast of the anchoring
      chorionic villi exhibited marked hyperproliferation and was classified as a
      proliferating mole. CONCLUSION: The intact early product of conception exhibited
      trophoblastic hyperplasia.

PMID- 11569421
TI  - [Psychological aspects of gynecologic operations].
AB  - OBJECTIVE: To make the stress influence of the hospitalisation on patients
      objective, to determine the factors in the process of therapy, which negatively
      influence a patient, and to find the consequences between the intensity of
      anxiety and the occurrence of the post-operational complications followed by the
      lengths of hospitalisation. DESIGN: Prospective clinical study. SETTING: The
      Department of Gynecology-Obstetrics of the General Teaching Hospital and the 1
      st. Medical Faculty of the Charles University in Prague. METHODS: 63 patients
      after the planned middle serious operation (abdominal or vaginal hysterectomy,
      Burche suspension and vaginal plastics) were included into the study. The women
      were not treated both because of oncological or psychiatric reasons and they did
      not suffer from some other serious illness. The mean age was 53, mean weight 72
      kg and mean parity 1.7. Evaluation of the stress influence of the patients was
      performed by means of the questionnaires, which were devised by us (Questionnaire
      A and B), and by means of standard questionnaires (STAI, SCL-90) that were filled
      in by the patients on the day of their reception and on the day of their release
      from the hospital. RESULTS: By evaluation of the questionnaires we have received
      objective parameters of the measure of anxiety and stress the patient is entering
      the treatment process with, and also subjective evaluation of the concrete stress
      moments occurring during the hospitalisation. A hypotheses proving that the more
      the stress load experienced by a patient the higher the probability of the
      occurrence of complications in the post-operational period and consequently
      longer hospitalisation has been verified by the methods of the statistic
      analyses. For our clinical praxis, the results of the descriptive analyses, where
      our patients evaluated their fear concerning the illness, its operational
      resolution and particular stress situations during hospitalisation, are mainly
      important. CONCLUSION: Our results proved that for ensuring optimal course of
      operation and post-operational period it is most important to reduce stress
      influence on a patient, i.e. particularly by a personal discussion of a surgeon
      and a treating doctor with the patient, and by elimination of the negative
      factors during the period of hospitalisation. Last but not least the most
      important role plays the clinical psychologist because not only important is
      professional medical, but also psychological access to the patient.

PMID- 11569422
TI  - [Effect of salpingectomy on the results of IVF in women with tubal sterility-
      prospective study].
AB  - OBJECTIVE: To compare the IVF results after salpingectomy of hydrosalpinges
      visible on ultrasound with IVF results in women with tubal infertility but
      without hydrosalpinx. DESIGN: Prospective study. SETTING: Sanatorium Pronatal, Na
      Dlouhe mezi 4/12, 147 00, Praha 4. METHODS: 101 women with tubal factor
      infertility were evaluated. In a prospective study we compared the results of
      first IVF cycle after salpingectomy of hydrosalpinges visible on ultrasound
      performed in 51 women (study group) with IVF results of 50 women with tubal
      infertility (confirmed by HSG and laparoscopy) but without hydrosalpinges and
      without salpingectomy. RESULTS: The maternal age in both groups (32.4 +/- 3.9 in
      salpingectomy group and 33.0 +/- 4.1 in control group), maximum estradiol levels
      (1392.6 +/- 675.8 pg/ml in salpingectomy group vers. 1624.7 +/- 909.7 pg/ml in
      control group), number of oocytes (11.3 +/- 5.8 after salpingectomy vers. 11.0 +/
      6.1 in controls), number of embryos generated (7.1 +/- 4.6 vers. 7.9 +/- 4.7)
      and number of embryos transferred were not statistically different. In their
      first IVF cycle after salpingectomy has been performed 30 women out of 51 became
      clinically pregnant (58.8%), while in control group a clinical pregnancy could be
      verified in 16 women (32.0%). Implantation rate in women after salpingectomy was
      28.2% vers. 12.3% in control group. Both implantation rate and pregnancy rate
      were statistically different at 5% level of significance. CONCLUSION: After
      salpingectomy of hydrosalpinges visible on ultrasound the implantation rate and
      clinical pregnancy rate are significantly better when compared to IVF patients
      with tubal infertility without the presence of hydrosalpinges and without
      salpingectomy. Salpingectomy should be offered to all patients with
      hydrosalpinges visible on ultrasound. Moreover, this radical approach should be
      considered even in women with highly damaged tubes but without the presence of
      hydrosalpinges.

PMID- 11569423
TI  - [Effect of psychological factors on success of in vitro fertilization].
AB  - OBJECTIVE: To examine the influence of psychological factors on outcome of in
      vitro fertilisation (IVF). DESIGN: Prospective clinical study. SETTING:
      Department of Gynaecology and Obstetrics, Charles University School of Medicine
      and General University Hospital Prague. METHODS: Sixty-six couples undergoing IVF
      treatment were administered psychometric tests: State-Trait Anxiety Inventory,
      Beck's Depression Inventory, Interpersonal Check List and Dusin Frustration Test.
      Results of pregnant and non-pregnant group were compared. RESULTS: We found
      statistically significant differences only in women. Women from the pregnant
      group had significantly lower scores of trait anxiety then women from the non
      pregnant group (P < 0.05). Pregnant women evaluated themselves (P < 0.01) and
      their partners (P < 0.01) as more hostile then the non-pregnant women in the ICL.
      In the scores of trait anxiety, depression and frustration were not any
      differences. In the non-pregnant group were the women significantly more anxious
      (state anxiety P < 0.02, trait anxiety P < 0.01) and depressed (P < 0.05) then
      their partners. We didn't find these differences in the pregnant group.
      CONCLUSION: Women from the pregnant group had significantly lower scores of trait
      anxiety then women from the non-pregnant group. Those women react in IVF
      treatment with higher stress and this stress response decreases their chance of
      conception. They were not any differences between the two groups of man. We found
      significant differences in the interpersonal interaction. In the non-pregnant
      group had the women significantly higher scores of depression and both state and
      trait anxiety. In the ICL evaluated themselves and their partners as more
      affiliate then the women in the pregnant group. According our opinion adequate
      hostility protects the women for depression and anxiety and is better coping
      style.

PMID- 11569424
TI  - [Analysis of factors affecting the results of assisted reproduction using a
      system for information mining of the SHLUK database].
AB  - OBJECTIVE: To retrospective explorating computer analysis of data about
      therapeutic cycles in assisted reproduction technology (ART) to confirm
      applicability of system for data mining SHLUK in partial analysis of
      fertilisation phase of therapeutic cycle. Relations between parameters of sperm
      count analysis and outcome of in vitro fertilisation were analyzed. DESIGN:
      Retrospective analysis. SETTING: 1st Depart of Obstet. and Gynaecol., Masaryk
      University, Brno; FEI, VSB, Ostrava. METHODS AND MATERIAL: Conditions of
      successful therapy in single phases of ART therapeutic cycles, were analysed
      using system SHLUK, which included a lot of methods for data mining. Analysis of
      relation between reasons and results in ART therapeutic cycles was done through
      method IMPL and method of group implication GRIMPL. Analysed file included data
      about 8516 therapeutic cycles ART in 4470 patients and data about 666 clinical
      pregnancies stored in electronical form in clinical data register. The model
      analysis of fertilisation tested relations between parameters of sperm analysis
      and outcome of in vitro fertilisation. Fertilisation rate (FR)--ratio of
      fertilized oocytes/obtained oocytes was evaluated as fertilisation stage outcome.
      RESULTS: Significantly higher FR--60.9% was in the group with sperm concentration
      before preparation 41-60 mil/ml. When sperm concentration before preparation was
      under 10 mil/ml--FR was significantly lower--42.2%. Motility of sperm before
      preparation under 10%--FR was significantly lower--45.3%. Motility of sperm
      before preparation 41-50%--FR was significantly higher--56.9%. Significantly
      higher FR--minimal 56.0% was in group of examinations with sperm after
      preparation was 41-90%, then FR was significantly higher--53.5%. In sperm
      survival test, where more than 30% of sperm survive 24 hours of cocultivation
      with oocytes FR was significantly higher--minimal 55.9%. CONCLUSION:
      Applicability of system for data mining SHLUK in the analysis of factors with
      influence on assisted reproduction outcome was proved. System for data mining
      SHLUK makes possible to define statistically significant relations between
      attributes of fertilisation stage of ART cycles and it is able to postulate basic
      hypothesis about existing reasons and results in therapeutic cycles of ART.

PMID- 11569425
TI  - [Current views on the etiopathogenesis of preeclampsia].
AB  - OBJECTIVE: To present a review of literature and to present our experiences of
      patients with preeclampsia. DESIGN: Review article. SETTING: Second Clinic of
      Gynecology and Obstetrics, Medical Faculty of the Safarik University and L.
      Pasteur's Hospital, Kosice, Slovak Republic. METHODS: Compilation of data from
      scientific literature. RESULTS AND CONCLUSION: The etiology of preeclampsia is
      still unknown. The 4 hypotheses currently accepted are the placental ischemia
      hypothesis, genetic hypothesis, the immune maladaption and hypothesis of the
      imbalance between free oxygen radicals and scavengers in favor of oxidants. At
      the present is most popular the theory of oxidative stress, that lead to
      increased production of lipide peroxides, tromboxane A2 and decreased level of
      prostacyclin. This imbalance triggers endothelial dysfunction and its clinical
      manifestation. Scavenging antioxidants have protective effect in this process.

PMID- 11569426
TI  - [PAPP-A in the first trimester of pregnancy].
AB  - OBJECTIVE: Pregnancy-associated plasma protein A has been reported to be low in
      Down syndrome affected pregnancies during the first trimester of pregnancy. The
      aim of this study was to determine preliminary the medians of pregnancy
      associated plasma protein A (PAPP-A) in the first trimester of pregnancy and to
      compare PAPP-A with other biochemical markers used for biochemical prenatal
      screening. DESIGN: Retrospective study. SETTING: First Institute of Medical
      Chemistry and Biochemistry and Institute for Clinical Biochemistry, First Medical
      Faculty, Charles University. Institute for Care of Mother and Child, Prague.
      PATIENTS: One hundred forty one pregnant women, who undergo biochemical prenatal
      screening for chromosomal disorders between 7th and 13th week were studied. In
      addition six women in the second trimester and five women with twin pregnancies,
      two cases of trisomy 21 and one case of trisomy 18 in second trimester were
      available for study. METHODS: Maternal serum levels of PAPP-A, human chorionic
      gonadotropin (hCG) and alfa-1-feto-protein (AFP) were measured using ELISA
      methods. A single radial immunodiffusion was used to determine trophoblast
      specific-beta-1-glycoprotein (SP1). RESULTS: PAPP-A levels increased throughout
      the first trimester with median 1.8 mg/l in the 7th week to 23.0 mg/l in the 13th
      week of pregnancy. PAPP-A serum levels from 3 women with twin pregnancies were
      higher than in women with singleton pregnancies. Serum levels of PAPP A in two
      women with fetus affected by chromosomal disorders did not differ from normal
      pregnancies. Correlation coefficients between PAPP-A and AFP and between PAPP-A
      and SP1 were statistically significant (r = 0.42, P < 0.001, respectively r =
      0.54, P < 0.001). The levels of PAPP-A and HCG did not correlate significantly (r
      = 0.019, P = 0.82). CONCLUSION: We established first trimester medians for PAPP
      A, which are necessary for evaluation of the pathological values. We found
      statistically significant correlation between PAPP-A and SP1 and PAPP-A and AFP.

PMID- 11569427
TI  - [Characteristics of a population of drug dependent pregnant women in the Czech
      Republic].
AB  - OBJECTIVE: The aim of the study was to characterise the population of drug abused
      pregnant women in Czech republic and chart their socioeconomic situation. DESIGN:
      Prospective study. SETTING: The Department of Gynaecology and Obstetrics of the
      General Teaching Hospital and the 1st Medical Faculty of Charles University in
      Prague. METHODS: This prospective study coursed since January 1998 till the end
      of the year 2000. This study covered a group of pregnant women addict on illegal
      drugs (heroin, pervitin). The group was set in close cooperation with Prague's
      contact anti-drugs centers (DROP-IN, K-centrum, Sanopin), Dependence therapy
      department and Department for genetics Teaching hospital Prague and of course in
      cooperation with the district gynaecologists. During 3 years we succeeded in
      gathering 41 addict women for prenatal care. Twenty of them were heroin and 18
      pervitin addict. The control groups were selected by method of accidental choice.
      We compared each group with its control and both groups of addicted mutually. We
      focused mainly on characteristics which could have a negative impact on the
      course of pregnancy, labour and lying-in period and the health condition of the
      foetus and the neonate (age, status, employment, parity, length of drug abuse,
      mode of application, attempt of therapy or abstinence, STD, hepatitis B and C,
      quality of prenatal care). RESULTS: We proved, that drug abused pregnant women
      are statistically significantly younger than pregnant women from control groups
      (by equal parity), mostly single and unemployed. The majority of them prefer
      intravenous way of drug application. The heroin--addict choose this type of
      application statistically significantly more often (94.4%) and also more often
      they report efforts at abstinence or therapy. A big part of drug abused pregnant
      women has insufficient prenatal care. 33% of heroin-addict and 25% of pervitin
      addict never attended the obstetrician during their pregnancy. We revealed a
      significantly higher incidence of HBsAg a mainly anti HCV and active hepatitis C
      among women from both "drugs" groups compared to their controls. We did not
      encounter any HIV positive case among the Czech addict pregnant. CONCLUSION: The
      population of drugs-addict pregnant women may be characterised as a high risk
      group from the view of prenatal care. The pregnancy is not a sufficient impulse
      for the majority of drugs-addict women to change their life stereotypes.

PMID- 11569428
TI  - [Analysis of maternal mortality in the Czech Republic in 1999].
AB  - OBJECTIVE: Analysis of maternal mortality in the Czech Republic in 1999. DESIGN:
      Retrospective statistical and clinical analysis. SETTING: Department of
      Obstetrics and Gynecology of the 1st Medical School of Charles University and
      General University Hospital, Prague 2; 2. Institute for Care of Mother and Child,
      Prague-Podoli. METHODS: We used database of 10 cases of maternal deaths in the
      Czech Republic during 1999 to analyze their causes, clinical courses especially
      related to obstetrical surgery, adequacy of provided care, and characteristics of
      their occurrence. RESULTS: There were total 10 reported maternal deaths in
      pregnancy, during labor or within 42 days after delivery in the Czech Republic in
      1999. During the same period there were 89,471 live births in the Czech Republic,
      and Pregnancy-related mortality ratio (A + B + C) was 0.11@1000, i.e. 11.2 deaths
      per 100,000 live births. This is about 0.044@1000 worse than in 1998 (the last
      table demonstrates the development of maternal mortality during last 9 years).
      One reported death was unrelated to gestation (category C), therefore adjusted
      maternal mortality rate (A + B) was 0.10@1000, i.e. 10.1 deaths per 100,000 live
      births versus 6.63 deaths per 100,000 live births in 1998. Group A (specific risk
      -direct maternal mortality) contributed to adjusted maternal mortality by 6
      maternal deaths and direct maternal mortality was 6.7 per 100,000 live births.
      Group B (non-specific risk--undirect maternal mortality) contributed by 3
      maternal deaths and undirect maternal mortality was 3.3 per 100,000 live births.
      CONCLUSION: The increase of maternal mortality in 1999 and forensic impact of
      some cases indicate the necessity to respect established guideline for obstetrics
      and gynecology. Currently established complex prophylactic measures to prevent
      development of thrombembolic complications provede, if fully implemented,
      possibility to minimize these threatening and formerly very frequent situations
      leading to death. However, there is ongoing danger of hemorrhagic complications
      related to the DIC, which despite the modern therapy represent the major factor
      in maternal mortality and morbidity.

PMID- 11569429
TI  - [Combined oral contraceptives with extremely low doses of estrogen (15 micrograms
      in a single tablet)].

PMID- 11569430
TI  - Impact of TriCare/managed care.

PMID- 11569431
TI  - Patient movement in the Pacific.

PMID- 11569432
TI  - The military healthcare system.
AB  - Throughout our Nation's history, healthcare has been a prominent issue for the
      military. TRICARE is the managed healthcare program for active duty and retired
      members of the uniformed services, their families, and survivors. During the past
      few years, the Joint Chiefs of Staff have put forth a concerted effort to work
      with the Congress and the Administration to ensure that TRICARE provides high
      quality healthcare for all members of the uniformed services, our retirees, and
      their families. Ensuring quality medical care for military retirees honors a
      promise made to those currently serving and to those who served their country in
      the past.

PMID- 11569433
TI  - Commitment.
AB  - Many trends in military medicine and civilian medical practice portend change
      that is unsettling to physicians. Historically, the medical profession has
      responded to patients' needs with both the art and the science of medicine. Many
      of the lessons learned regarding humanism in medicine are worth repeating. It is
      the job of physicians as teachers to keep bringing us back to certain basic
      principles. Commitment to God, country, honor, courage, leadership, and teaching
      should be stressed among those principles. Military physicians must also develop
      an attitude regarding their dual officer/doctor role because military and medical
      objectives may present difficult ethical decisions. In addition, observance of
      time-honored customs and traditions can bring a sense of justifiable pride to the
      physician caring for our nation's military members, their families, and retirees.

PMID- 11569434
TI  - Shaping the medical environment in Kosovo through engagement.
AB  - Operation Joint Guardian in Kosovo represents one type of military operation that
      the United States and other nations could be engaged in during the next 25 years.
      These military operations also carry unique challenges to a senior medical
      officer (or medical task force commander). In Kosovo, the senior medical officer
      had to help shape the medical environment as the military coalition sought to
      restore a safe and secure environment. This article discusses medical engagement
      strategies specific to Kosovo, where helping to shape the medical environment
      demanded that the senior medical officer engage with other coalition nations,
      United Nations (U.N.) agencies, and selected Kosovar health care providers.
      Successful implementation of the U.N. health care strategy is one of the key
      elements of U.N. success and the military coalition's exit from Kosovo. The goal
      of this report is to form a template for medical engagement strategies that a
      future senior medical officer may use in other similar military operations.

PMID- 11569435
TI  - Investigation of a cluster of Legionella pneumophila infections among staff at a
      federal research facility.
AB  - An epidemiologic investigation was conducted in response to a case of Legionella
      pneumonia in a scientist working at a federal research facility. A survey of 80
      individuals working at the facility revealed that 13 (16%) had sustained prior
      infections with Legionella pneumophila serogroup 1 (Lps1) as measured by anti
      Lps1 antibodies. Antibody-positive individuals' offices clustered around an air
      cooling tower and a heating, ventilation, and air conditioner unit (odds ratio =
      5). On multivariate logistic regression analysis, individuals of non-white race
      (adjusted odds ratio = 8) and smokers (adjusted odds ratio = 36) were also found
      to be at higher risk of past infection. Marked Legionella growth was noted in the
      cooling tower's water reservoir and potable hot water system, where suboptimal
      operating temperatures were noted. Subsequent increase in the hot water
      temperatures as well as a complete renovation of the affected building's air
      handling and potable water systems led to a reduction in Legionella species
      colonization.

PMID- 11569436
TI  - Prospective study of respiratory infections at the U.S. Naval Academy.
AB  - Midshipmen at the U.S. Naval Academy have recently suffered epidemics of upper
      respiratory tract infections. Seeking to determine cause, in June 1998 we
      enrolled 1,243 (99.5%) of 1,249 new midshipmen (plebes) and followed them during
      their first 11 months of training. Eighty-five plebes sought medical attention
      for acute respiratory disease. Using culture, serologic studies, and polymerase
      chain reaction, considerable evidence for respiratory pathogen infection was
      found among the ill subjects: Chlamydia pneumoniae in 41 (52.6%), Mycoplasma
      pneumoniae in 19 (25.3%), influenza in 11 (14.2%), Streptococcus pneumoniae in 6
      (7.3%), and adenovirus in 1 (1.2%). Additionally, 873 (81%) the 1,077 plebes who
      completed an end-of-year questionnaire complained of having one or more
      respiratory symptoms (> 12 hours) during their first year of school. Of these,
      132 (15%) reported that the symptoms significantly affected their performance.
      Study results suggest that respiratory infections were frequent, had a
      significant adverse impact on training, and were often attributable to bacterial
      pathogens.

PMID- 11569437
TI  - Latex allergy literature review: evidence for making military treatment
      facilities latex safe.
AB  - Latex allergy has become the epidemic of the 1990s for health care workers, as
      indicated by a remarkable increase in its prevalence. This literature review
      provides a brief background to the latex problem, strategies for prevention and
      management, a cost analysis of glove substitution in a clinical setting, and the
      implications for the military environment. Primary care providers must recognize
      the financial, medico-legal, occupational, and personal ramifications of latex
      allergy. Risk managers should realize that moving to a latex-free environment
      will reduce liability.

PMID- 11569438
TI  - Analyzing process variation in chart review using a networked spreadsheet
      application in the Walter Reed Army Medical Center Nephrology Clinic.
AB  - The role of reviewer variation in interpreting outcomes of outpatient clinic
      chart reviews has been poorly studied. The present study used results collected
      from a network-based spreadsheet application (Microsoft Excel), which is widely
      available throughout the Army Medical Department, for chart reviews. Data were
      collected from January 1998 to August 2000, and 2,308 charts of 1,127 patients
      were reviewed. Results showed a significant improvement in documentation of
      contact with the referring provider from 1998 to 2000 (55.9% in 1998, 81.6% in
      1999, and 80.6% in 2000; p < 0.01 by chi 2 for both). The percentage of charts
      for new consultations with inadequately controlled blood pressure managed
      appropriately improved from 73.7% in 1999 to 89.2% in 2000 (p < 0.01 by chi 2).
      These results persisted in logistic regression analysis controlling for different
      reviewers. In conclusion, widely available office automation tools allow the
      systematic analysis of chart review data with the potential to improve practice
      patterns.

PMID- 11569439
TI  - Cigarette smoking in the Oregon Air National Guard: findings from a health
      promotions survey.
AB  - The purpose of this study was to assess the prevalence of smoking among
      demographic subgroups in the Oregon Air National Guard (ORANG), examine
      demographic predictors of current smoking, and describe interest in smoking
      cessation classes. During the autumn of 1995, 1,000 surveys were distributed
      through unit medical liaisons to ORANG personnel. A total of 589 (59%) surveys
      were returned. Overall smoking prevalence was 19%. The percentage of smokers who
      reported heavy smoking (one or more packs per day) was highest among enlisted
      personnel in the middle (46.9%) and highest (71.4%) pay grades and in the oldest
      age group (63.4%). Cigarette consumption per day was significantly higher in the
      oldest age group (F = 3.92, df = 3/107, p < 0.01). In separate logistic
      regression models, neither age, full-time technician vs. traditional National
      Guard status, nor pay grade were significant predictors of smoking in either
      enlisted or officer personnel. Substantial interest in smoking cessation programs
      was identified.

PMID- 11569440
TI  - Soldier acceptability of a camouflage face paint combined with DEET insect
      repellent.
AB  - Under operational conditions, current doctrine requires separate application of
      the standard military insect repellent and camouflage face paint. Working with an
      industrial partner, Amon Re, Inc., we developed a combined camouflage face paint
      and insect repellent that offers excellent protection from arthropod disease
      vectors. We undertook a study to determine whether the new product was acceptable
      to soldiers under field conditions. A new formulation of camouflage face paint
      containing the insect repellent N,N-diethyl-3-methyl-benzamide (DEET) was tested
      for user acceptability during a joint-service, multinational, military field
      training exercise (Operation Cobra Gold 1999) in Thailand. Soldiers testing the
      camouflage face paint were members of one of three companies (A, B, and C) of 1st
      Battalion, 21st Infantry Regiment, 25th Infantry Division. Soldiers in A company
      (N = 98) received standard military camouflage face paint and the U.S. military's
      Extended Duration Topical Insect and Arthropod Repellent containing 33% DEET,
      soldiers in B company (N = 75) received a new formulation of camouflage face
      paint without DEET, and soldiers in C company (N = 88) received the new
      formulation of camouflage face paint containing 30% DEET. Every soldier who
      volunteered to participate completed the study and submitted responses to the
      questionnaire. The different treatments were evaluated while soldiers spent 4
      days conducting simulated combat exercises in a hot, tropical environment in
      central Thailand. Soldiers were provided the test materials, given a briefing on
      the study, and completed an initial questionnaire on May 19, 1999. Soldiers
      completed a final questionnaire after they returned from the training exercise on
      May 24, 1999. Results of the study indicated that soldiers found the new
      formulation of 30% DEET camouflage face paint easier to apply (88% of
      respondents) and remove (77%) than the current standard issue camouflage face
      paint. Soldiers liked the new 30% DEET camouflage face paint formulation better
      (61%) and were more likely to recommend it (67%) than the old camouflage face
      paint formulation. Although the addition of DEET to the camouflage face paint
      occasionally caused minor irritation after application for a short period (less
      than 15 minutes), the new camouflage face paint formulation with 30% DEET was
      evaluated most often (72%) as either good or excellent. The new 30% DEET
      camouflage face paint formulation offers significant operational advantages:
      protection from disease-transmitting arthropods, elimination of the need to carry
      separate insect repellent and camouflage face paint, and reduction in the time
      required to apply repellent and camouflage face paint separately.

PMID- 11569441
TI  - Operation shadow warrior: a quantitative analysis of the ultraviolet radiation
      protection demonstrated by various headgear.
AB  - In the last 10 years, the scientific community and the media have highlighted the
      depletion of atmospheric ozone and the subsequent increase in ultraviolet
      radiation (UVR) that penetrates to the earth's surface. This UVR is associated
      with problems such as sunburn, photoaging, cataracts, and skin cancer. In the
      United States, skin cancer is among the top three reported cancers, and its
      incidence is increasing rapidly. Physicians agree that human exposure to UVR
      should be controlled by protecting the skin or limiting its exposure to UVR. As
      military physicians, our mission is to protect the fighting force and educate the
      command on the best possible course of action to accomplish this mission. In this
      paper, I quantitatively demonstrate that wearing the inventoried sun, woodland,
      type III cover is a far superior course of action when a commander desires a UVR
      counter measure for the fighting force.

PMID- 11569442
TI  - Air Force family nurse practitioner and family physician perception of the family
      nurse practitioner role in military operations other than war.
AB  - The inevitable result of changing world events and defense requirements is that
      the family nurse practitioner (FNP) will take on a more active role in the
      deployed setting, especially in military operations other than war. What is the
      perception of the FNP and family physician of the role of the FNP in these
      missions? Because of the collaborative role between these two provider groups, it
      is important to compare these perceptions to ensure quality collaborative care.
      Respondents were requested to rate their perceptions regarding the ability of the
      FNP to treat 65 categories of patients. Analysis revealed that there was a
      significant difference among the providers concerning the FNP role. Several
      perceived barriers were also identified. Because of this difference, the FNP may
      not be fully utilized. In addition, this study provides insight regarding the
      training needs perceived to adequately prepare FNPs for their deployment role.

PMID- 11569443
TI  - Forward surgical stabilization of penetrating lower extremity fractures: circular
      casting versus external fixation.
AB  - OBJECTIVE: There are two choices for the stabilization of penetrating lower
      extremity fractures in the forward surgical environment: bivalved circular
      casting and external fixation. The material and equipment requirements of these
      methods are of paramount importance in the austere forward surgical environment.
      METHODS: Casualties from the Battle of the Black Sea in Somalia 1993 were
      examined. Penetrating lower extremity fractures requiring immobilization were
      identified. The relative packing volume and weight for each method of
      immobilization were analyzed. Finally, the current literature concerning the
      treatment of penetrating lower extremity fractures sustained in combat was
      reviewed. RESULTS: The consumable material requirements of cast immobilization
      are 22.9 times greater by weight and 3.16 times greater by packing volume. Cast
      immobilization also has a greater durable equipment requirement. External
      fixation has multiple clinical advantages but is considerably more expensive.
      CONCLUSION: Based on these variables, the authors determined that external
      fixation is the treatment of choice for penetrating lower extremity fractures in
      the forward surgical environment.

PMID- 11569444
TI  - Physical symptoms as indicators of depression and anxiety.
AB  - Psychological problems are the single most common reason for attrition from U.S.
      Navy basic training. A contributing factor is that, although military entrance
      processing station physicians assess numerous aspects of physical health, there
      is little rigor behind attempts to identify psychological disorders. In the
      present study, we highlight previous research indicating that patterns of
      physical health symptoms can provide a gauge of psychological dysfunction. We
      also report significant relationships between physical symptoms, anxiety, and
      depression in a sample of more than 2,000 sailors. Therefore, given the links
      between physical symptoms and psychological problems, it may be feasible for
      physicians who screen military applicants to use routinely gathered physical
      health information as part of an improved system to detect psychological
      disorders.

PMID- 11569445
TI  - Job satisfaction, occupational stress, and personality characteristics of Air
      Force military training instructors.
AB  - The authors present findings from the preliminary stage of a research program
      intended to improve the selection and retention of U.S. Air Force military
      training instructors (MTIs). Data derived from an initial sample of 100 incumbent
      instructors are discussed. Global job satisfaction and occupational stress
      levels, along with normal personality traits measured by the Revised NEO
      Personality Inventory, are presented. Results indicate a wide range of reported
      job satisfaction and stress among MTIs, with a sizable proportion indicating that
      they would not volunteer for this duty again. Several personality characteristics
      appear to be salient in distinguishing satisfied and adaptive MTIs from those who
      are unsatisfied and coping poorly. The authors outline plans for the long-term
      continuation and expansion of the project to develop an empirically based
      selection system for the MTI career field.

PMID- 11569446
TI  - Long-term heart disease and stroke mortality among former American prisoners of
      war of World War II and the Korean Conflict: results of a 50-year follow-up.
AB  - For the first 30 years after repatriation, former American prisoners of war
      (POWs) of World War II and the Korean Conflict had lower death rates for heart
      disease and stroke than non-POW veteran controls and the U.S. population, but
      subsequent morbidity data suggested that this survival advantage may have
      disappeared. We used U.S. federal records to obtain death data through 1996 and
      used proportional hazards analysis to compare the mortality experience of POWs
      and controls. POWs aged 75 years and older showed a significantly higher risk of
      heart disease deaths than controls (hazard ratio = 1.25; 95% confidence interval,
      1.01-1.56), and their stroke mortality was also increased, although not
      significantly (hazard ratio = 1.13; 95% confidence interval, 0.66-1.91). These
      results suggest that circulatory disease sequelae of serious, acute malnutrition
      and the stresses associated with imprisonment may not appear until after many
      decades.

PMID- 11569447
TI  - Disruption of gas exchange in mice after exposure to the chemical threat agent
      phosgene.
AB  - The use of chemical warfare agents, such as the pulmonary irritant gas phosgene,
      is a real and constant threat not only from belligerent nations but from
      terrorist groups as well. Phosgene is both easy and inexpensive to produce and as
      such is a potential candidate for use as a threat agent. Phosgene attacks the
      deep lung after inhalation and can severely compromise pulmonary mechanics and
      gas exchange, rendering the exposed individual incapacitated. If exposure is
      severe, death can ensure by asphyxiation secondary to pulmonary edema formation.
      This paper examines the effects on lung tissue in mice over 24 hours after
      exposure to the irritant gas phosgene. Exposure to phosgene produced respiratory
      acidosis by decreasing pH, partial pressure of oxygen, O2 saturation, and
      increasing partial pressure of carbon dioxide. Exposure to phosgene also induced
      temporal increases in lung tissue gravimetric parameters such as lung tissue wet
      weight/dry weight ratio, which is a positive indicator of pulmonary edema
      formation, and dry lung weight, an indicator of lung cellular hyperaggregation.
      Blood gases and pH tend to normalize within 24 hours, whereas gravimetric
      parameters remain increased. Temporal changes in these physiological indicators
      of lung injury may help to explain why past exposures to phosgene required
      lengthy hospitalization.

PMID- 11569448
TI  - The medical civic action program in Vietnam: success or failure?
AB  - Medical services have long been an integral part of the military and warfare.
      Civilians, however, are also caught up in wars. This article discusses the care
      of the indigenous civilians by U.S. military medical personnel during the Vietnam
      War. Civilian medical care is rendered both for altruistic purposes and to
      satisfy the policy aims of the U.S. government. Evaluation of these two aspects
      of the programs does not lead to the same conclusions. Doctors doubted the value
      of the programs, whereas the command structure was enthusiastic. For a program to
      be of sustained value to the people, it must persist over time and train those
      who will remain after U.S. forces are withdrawn. This did not occur in Vietnam.
      Furthermore, I doubt that medical care rendered by U.S. troops in uniform can
      serve to build up loyalty to another organization, such as the host government.

PMID- 11569449
TI  - The physical training and rehabilitation program: duration of rehabilitation and
      final outcome of injuries in basic combat training.
AB  - During calendar year 1998, 6% (N = 2,010: men [m] = 670, 3%, women [w] = 1,340,
      12%) of soldiers in basic combat training at Fort Jackson, South Carolina (N =
      32,251), were unable to continue training as a result of a training-related
      injury. These soldiers were recommended for the Physical Training and
      Rehabilitation Program (PTRP) for recovery and rehabilitation. Forty-two percent
      of recommended soldiers were discharged from the Army rather than assigned to
      PTRP. The 1,164 (m = 356, w = 808) soldiers assigned to PTRP sustained 1,673
      injuries (m = 444, w = 1229). Eighty-three percent of the injuries in PTRP were
      in the overuse (44%) and stress fracture (39%) categories. Of the 1,164 soldiers
      assigned to PTRP, 52% (m = 214, w = 386) returned to training. The average (+/-
      SD) length of stay in PTRP for soldiers returning to duty was 62 +/- 42 days (m =
      57 +/- 39, w = 65 +/- 43). Rehabilitation challenges and significant motivational
      issues presumably contributed to the 52% return to duty incidence for PTRP
      soldiers.

PMID- 11569450
TI  - Goodpasture's syndrome: a case of delayed appearance of autoantibodies and renal
      disease.
AB  - Goodpasture's syndrome, or anti-glomerular basement membrane (anti-GBM) disease,
      is a rare pulmonary-renal syndrome that results from autoantibody-mediated
      destruction of alveolar and glomerular basement membranes. It is defined by the
      triad of pulmonary hemorrhage (hemoptysis), glomerulonephritis (hematuria), and
      circulating anti-GBM antibodies. Although kidney disease can occur with or
      without lung involvement, isolated alveolar hemorrhage as an incipient
      manifestation of the syndrome is rare. We report the case of a patient with anti
      GBM disease who initially presented with seronegative hemoptysis and normal
      urine. It was not until relapse of his condition that we found acute
      glomerulonephritis and circulating antibodies. In this report, we briefly review
      the pathogenesis and clinical manifestations of anti-GBM disease and discuss the
      relevance of isolated alveolar hemorrhage.

PMID- 11569451
TI  - Adenocarcinoma of unknown primary site presenting as an isolated retroperitoneal
      mass and Trousseau's syndrome.
AB  - BACKGROUND: There are few reported cases of adenocarcinoma of unknown primary
      site (ACUPS) presenting with Trousseau's syndrome, and no cases presenting as an
      isolated retroperitoneal pelvic mass. CASE: This is a case of a 36-year-old woman
      who presented with an isolated "pelvic" mass and Trousseau's syndrome. The
      patient underwent abdominal hysterectomy and bilateral salpingo oophorectomy with
      resection of the retroperitoneal lymph nodes. Surgical findings included normal
      appearing uterus, fallopian tubes, and ovaries, with bilaterally enlarged pelvic
      lymph nodes. Pathology was positive for adenocarcinoma only in the pelvic lymph
      nodes. Uterine, ovarian, and fallopian tube final pathologies were negative for
      malignancy. Postoperative metastatic survey was negative, and the patient was
      diagnosed with ACUPS. The patient received adjuvant chemotherapy consisting of
      etoposide, carboplatin, and taxol. The patient died 18 months after diagnosis.
      CONCLUSION: This case reminds us that ACUPS can present as Trousseau's syndrome
      and rarely as an isolated retroperitoneal pelvic mass.

PMID- 11569452
TI  - Cardiac asystole after mouthwash ingestion: a case report and review of the
      contents.
AB  - In the search for intoxication, alcoholic patients often ingest toxic alcohols or
      other products containing ethanol. We report a patient who presented with
      intoxication from Listerine and rapidly progressed to cardiac asystole. Several
      mouthwash products have a high concentration of ethanol and are easily obtained.
      We review the contents of this product and their possible toxicologic effects.

PMID- 11569453
TI  - Public-private partnerships. Public pain, private gain.
AB  - Using private hospitals over 11 weeks this winter enabled a health authority to
      remove more than 1,000 patients from waiting lists. Prices were comparable to,
      and sometimes cheaper than, the NHS. The average cost was 1,120 Pounds per
      treatment. Patient satisfaction seemed high. Consultant productivity was higher
      in the private sector.

PMID- 11569454
TI  - Open space. Hazard lights.

PMID- 11569455
TI  - Primary care. Getting in on the act.
AB  - A three-year in-depth evaluation of 12 PCG/Ts shows that much remains to be done
      in terms of commissioning. PCG/Ts need to be more active in tackling poor
      performance. Further delegation of responsibilities from health authorities to
      PCTs will be a challenge, given their reluctance to tackle service changes. GPs
      tend to dominate board meetings. More resources are needed for management
      support.

PMID- 11569456
TI  - Counselling services. Strain spotting.

PMID- 11569457
TI  - Hepatitis prevention and control.

PMID- 11569458
TI  - Do men experience menopause?

PMID- 11569459
TI  - [Eosinophilic cellulitis (Wells syndrome)].

PMID- 11569460
TI  - [Cutaneous zygomycosis due to Absidia corymbifera].

PMID- 11569461
TI  - [Tubercular ulcers in a kickboxer].

PMID- 11569462
TI  - [CD56-positive 'natural killer'/T-cell lymphoma].

PMID- 11569464
TI  - [Lupus panniculitis].

PMID- 11569463
TI  - [Overlapping acute disseminated exanthematous pustulosis and toxic epidermal
      necrolysis].

PMID- 11569465
TI  - [Diffuse cutaneous mastocytosis].

PMID- 11569466
TI  - [Bullous congenital ichthyosiform erythroderma of Brocq; 2 patients with
      different phenotype and genotype].

PMID- 11569467
TI  - The ten most commonly asked questions about endothelial function in cardiology.

PMID- 11569468
TI  - Neuromuscular disorders: gene location.

PMID- 11569469
TI  - Mitochondrial encephalomyopathies: gene mutation.

PMID- 11569470
TI  - On the Penrose inequality.
AB  - The purpose of this Letter is to point out an argument which may ultimately lead
      to a rigorous proof of the Penrose inequality in the general case. The argument
      is a variation of Geroch's original proposal for a proof of the positive-energy
      theorem which was later adapted by Jang and Wald to apply to initial data sets
      containing apparent horizons. The new input is to dispense with the a priori
      restriction to an initial data set and to use the four-dimensional structure of
      spacetime in an essential way.

PMID- 11569471
TI  - Instantons and the DeltaI = 1/2 rule.
AB  - The instanton-induced interaction leads to a significant enhancement of the Ao
      weak amplitude determining the DeltaI = 1/2 rule, through the contribution of
      operators with dimension d = 9, as we show in the weak K--> pi(pi) decay.

PMID- 11569472
TI  - A case of Ganser syndrome: organic or hysterical?

PMID- 11569473
TI  - Sudden dysphagia with uvular enlargement following the initiation of risperidone
      which responded to benztropine: was this an extrapyramidal side effect?

PMID- 11569475
TI  - Update on the role of bisphosphonates in metastases. Proceedings of a meeting.
      San Antonio, Texas, USA. December 5, 2000.

PMID- 11569474
TI  - Even low-dose treatment of venlafaxine may provoke recurrence of hypertension in
      an Asian patient?

PMID- 11569476
TI  - The role of external beam radiotherapy with I-125/Pd-103 brachytherapy for
      prostate carcinoma.

PMID- 11569477
TI  - Modified dinucleoside tetraphosphonates, new potential inhibitors of HIV reverse
      transcriptase.
AB  - New gamma-substituted analogues of dNTP were synthesized and their enzymatic
      stability and antiviral properties were evaluated.

PMID- 11569478
TI  - [Hypertension, abdominal aortic aneurysm, chronic bronchitis and myeloid
      leukemia].

PMID- 11569479
TI  - Erythropoetin treatment can increase 2,3-diphosphoglycerate levels in red blood
      cells.
AB  - Some patients experience an improved well-being during treatment with recombinant
      human erythropoietin even with an unchanged Hb level. We have hypothesized that
      this may not be only a placebo effect. 2,3-diphosphoglycerate (2,3-DPG) in red
      blood cells increases in response to anaemia/hypoxia and causes a shift of the
      oxygen dissociation curve, allowing a more effective oxygen delivery. We have
      investigated red cell 2,3-DPG concentrations during erythropoietin treatment in
      healthy volunteers as a mediator of a possible physiological explanation.
      Thirteen healthy subjects with no iron deficiency were recruited and randomly
      assigned to a treatment group comprising five males and three females and a
      control group including three males and two females. The treatment group was
      treated with erythropoietin (Recormon), 20 IE/kg subcutaneously three times/week
      for 4 weeks. Blood samples were collected at each injection day and 10 days after
      the last injection and at corresponding times in the control group. B-Hb, red
      cell 2,3-DPG and P50 were measured by standard techniques and oxygen-releasing
      capacity was calculated. RESULTS: due to the sampling (26 ml each time, three
      times/week) the mean Hb level was lowered from 140.5 +/- 5.9 to 128.6 +/- 10.4
      g/L in the control group whereas the erythropoietin treatment group maintained a
      mean Hb level of about 142 g/L (p<0.002). The 2,3-DPG mean level curve as well as
      that for oxygen releasing capacity also differed significantly between the two
      groups (p < 0.002), the treatment group showing higher levels. CONCLUSION:
      treatment with erythropoietin causes an increase in red cell 2,3-DPG levels.

PMID- 11569480
TI  - Increased serum levels of carbohydrate-deficient transferrin in patients with
      chronic obstructive pulmonary disease.
AB  - OBJECTIVE: The reason that only a minority of smokers develop chronic obstructive
      pulmonary disease (COPD) is still largely unknown. Glycosylation defects are
      involved in the pathological mechanisms in cystic fibrosis (CF), where chronic
      progressive obstructive lung disease dominates the clinical picture. Whether
      defects of protein glycosylation occur in COPD has not previously been examined.
      Increase in carbohydrate-deficient transferrin (CDT) in serum seems to function
      as an indicator of general defects of N-glycosylation. Recently, one study
      observed high serum CDT concentrations in CF patients. We examined whether
      subjects with COPD also have increased serum CDT levels. METHOD AND RESULTS: A
      total of 131 randomly selected individuals, 45-64 years of age, underwent a
      medical examination, spirometry and blood tests. Serum CDT was determined using
      high performance liquid chromatography. In subjects diagnosed as having COPD (n =
      15), multiple logistic regression analyses demonstrated a significant
      relationship between the diagnosis of COPD and CDT, even after all efforts were
      made to take the influence of age and smoking into account (odds ratio 3.16, 95%
      CI 1.11-8.95). Also, in subjects with COPD there was an inverse partial
      correlation between forced expiratory volume in 1 s (FEV1) and serum CDT (r = 
      0.81, p = 0.001). CONCLUSION: These results suggest that protein glycosylation
      defects occur in COPD and, in addition, might be involved in the pathogenetic
      mechanisms of the disease. It seems that further investigation of the protein
      glycosylation in COPD is warranted.

PMID- 11569482
TI  - Development of enzyme immunoassays to detect salivary sIgA to Chlamydia
      pneumoniae and Mycoplasma pneumoniae.
AB  - Enzyme immunoassays (EIAs) for the detection of secretory IgA antibody (sIgA) to
      Chlamydia pneumoniae and Mycoplasma pneumoniae from saliva are described. The
      presence of salivary sIgA in healthy laboratory personnel (mean age 40, range 25
      62 years) was detected using conjugates of antibodies directed against secretory
      and alpha-chain domains. The EIA results for the detection of C pneumoniae sIgA
      antibodies were confirmed by a sensitive microimmunofluorescence method used as a
      reference. Circulating IgA antibody levels in sera were also determined using
      commercial EIAs. Secretory IgA antibodies to both C pneumoniae and M. pneumoniae
      were detectable only from persons with positive or borderline circulating IgA
      antibodies. Moreover, C. pneumoniae sIgA was found in the saliva of a clinically
      healthy person whose serum IgA antibody levels had been constantly elevated
      during the past 7 years. In conclusion, because of their specificity the
      described methods could be used in further delineation of the role of anti-C
      pneumoniae and M. pneumoniae sIgA antibodies. However, owing to the unexpected
      high frequency of these antibodies in saliva of clinically healthy persons, it
      seems unlikely that a single sIgA measurement from saliva is diagnostically more
      powerful than a single IgA measurement from serum to study and interpret the
      involvement of these pathogens in chronic respiratory diseases.

PMID- 11569481
TI  - Lack of effect of fish oil supplementation on coagulation and transcapillary
      escape rate of albumin in insulin-dependent diabetic patients with diabetic
      nephropathy.
AB  - OBJECTIVE: We studied the effect of a diet supplementation with fish oil in
      insulin-dependent diabetic patients with nephropathy in order to evaluate whether
      abnormal transcapillary escape rate of albumin and procoagulant activity in these
      patients could be modified. METHODS: A double-blind, randomized, controlled study
      was carried out at a tertiary referral centre. The subjects were 29 insulin
      dependent diabetic patients with nephropathy. One year of fish oil
      supplementation (4.6 g n-3 fatty acids/day) was compared with placebo (olive
      oil). The main outcome measures were N-3 fatty acid proportions of platelet
      lipids, transcapillary escape rate of albumin, prothrombin fragment 1 + 2,
      thrombin-antithrombin complexes, markers of fibrinolysis, fibrinogen, factor VII
      antigen and activity, thrombomodulin, von Willebrand factor, platelet factor 4
      and beta-thromboglobulin. These were measured every 6 months. RESULTS: Neither
      transcapillary escape rate of albumin (7.4 (median) (5.0-9.8) (range) % vs. 7.0
      (4.6-10.6) %) nor prothrombin fragment 1 + 2 (0.97 (0.72-2.40) nmol/L vs. 1.01
      (0.59-3.11) nmol/L) changed after 12 months of fish oil supplementation.
      CONCLUSION: Increased transcapillary escape rate of albumin and activity could
      not be modified during diet supplementation with fish oil in insulin-dependent
      diabetic patients with nephropathy.

PMID- 11569483
TI  - CD4+ T-lymphocytopenia and systemic immune activation in patients with primary
      and secondary liver tumours.
AB  - Using flow cytometry, we evaluated peripheral blood leucocyte subsets in 84
      patients with primary and secondary liver cancer. The patients had significantly
      lower absolute (659+/-386 vs. 906+/-360 cells per microl, p=0.004) numbers of
      CD3+ CD4+, relative (9+/-5 vs. 12+/-4%, p=0.02) and absolute (154+/-115 vs. 221+/
      83 cells per microl, p=0.02) numbers of CD8+ CD28+, absolute numbers of CD3+ and
      relative and absolute numbers of CD19+. Relative and absolute numbers of CD3+
      DR+, CD3+ CD69+ and CD14+ CD16+ cells were significantly elevated in patients
      compared to controls. The phenotype was similar in 54 patients exposed to
      chemotherapy compared to 30 untreated patients. Urinary neopterin, a marker of
      systemic immune activation, was significantly higher in patients with liver
      tumours compared to controls. A negative correlation was observed between urinary
      neopterin and the absolute numbers of CD3+ CD4+ (Spearman rank correlation
      coefficient, rs = -0.54, p<0.0025) and CD19+ (rs = -0.49, p<0.01) in untreated
      patients. We conclude that, independently of prior chemotherapy, patients with
      liver present with markedly decreased numbers of CD3+ CD4+ lymphocytes as well as
      with other abnormalities of peripheral blood leukocyte phenotype. Similar to
      patients with human immunodeficiency virus infection, the decrease in CD3+ CD4+
      lymphocytes is associated with systemic immune activation.

PMID- 11569484
TI  - Skeletal muscle glucose uptake, glycogen synthase activity and GLUT 4 content
      during hypoglycaemia in type 1 diabetic subjects.
AB  - In healthy subjects, hypoglycaemia induces a profound 80% reduction in skeletal
      muscle glucose uptake and a similar suppression of glycogen synthase activity.
      The aim of this study was to examine the efficacy of this counterregulatory
      mechanism in type 1 diabetic subjects, who are especially prone to hypoglycaemic
      incidents. Nine type 1 diabetic male subjects were examined twice; during 120 min
      of hyperinsulinaemic (1.5 mU x kg(-1) x min(-1)) euglycaemia followed by (i) 240
      min of graded hypoglycaemia (glucose nadir 2.8 mM) or (ii) 240 min of
      euglycaemia. At 345-360 min a muscle biopsy was taken and indirect calorimetry
      was performed at 210-240 and 320-340 min. The sensitivity of glycogen synthase to
      glucose-6-P was reduced by hypoglycaemia, as shown by an increase in A0.5 for
      glucose-6-P (at 0.07 mmol/L) from 0.21+/-0.02 to 0.28+/-0.03 mM (p=0.06).
      Likewise, the fractional velocity for glycogen synthase was reduced by 25%; i.e.
      from 20.8+/-2.0 to 15.5+/-1.4% (p<0.05). Total glucose disposal was decreased
      during hypoglycaemia (5.3+/-0.6 vs. 8.3+/-0.7 mg x kg(-1) x min(-1)
      (euglycaemia), n = 9; p<0.05), primarily due to a reduction of non-oxidative
      glucose disposal (2.7+/-0.3 vs. 5.1+/-0.6 mg x kg(-1) x min(-1) (euglycaemia),
      n=7; p<0.05). Forearm arteriovenous glucose differences were decreased by 50% in
      the hypoglycaemic situation (0.7+/-0.1 vs. 1.4+/-0.3 mmol/L (320-340 min)), and
      counterregulatory hormonal responses seemed less conspicuous than described in
      healthy subjects. We conclude that hypoglycaemia induces decrements of forearm
      glucose uptake and glycogen synthase activity in type 1 diabetic subjects. The
      study indicates a decreased magnitude of these responses, but this remains to be
      confirmed.

PMID- 11569485
TI  - Splanchnic and systemic hemodynamic effects of sustained euglycemic
      hyperinsulinemia in rats.
AB  - Insulin, in addition to its metabolic function, was found to induce skeletal
      muscle vasodilatation after acute administration. The vasoactive effects of
      sustained euglycemic hyperinsulinemia, especially in the splanchnic circulation,
      are less well known. The aim of this study was to evaluate the systemic and
      splanchnic hemodynamic effects of sustained euglycemic hyperinsulinemia.
      Hyperinsulinemia was induced by a sustained-release insulin implant in the scurf
      area of male rats (release rate -1 U/day). Beginning on the 3rd day, the study
      group was fed a glucose-rich diet. Hemodynamic studies were performed on the 5th
      day using the radioactive microsphere technique. Serum insulin was measured by
      radioimmunoassay. At the time of the hemodynamic measurements, plasma insulin
      level was higher in the insulin-treated (n=8) compared to control rats (n=8)
      (23.6 +/- 4.7 vs. 13.2+/-3.9 microu/mL, respectively; p<0.001). Plasma glucose
      level of the two groups was similar (5.43 +/- 1.07 vs. 5.83 +/- 1.44 mmol/L,
      respectively). Abdominal skeletal muscle blood flow was higher in the insulin
      treated group (0.11 +/- 0.05 vs. 0.05 +/- 0.04 mL x min(-1) x g(-1),
      respectively; p<0.02). No significant changes were observed in cardiac output and
      renal blood flow. In the splanchnic circulation: stomach, pancreatic, intestinal,
      splenic, hepatic arterial and total hepatic blood flow were also not
      significantly different. In summary, short-term, sustained euglycemic
      hyperinsulinemia in rats increased blood flow to skeletal muscle but had no
      hemodynamic effects on cardiac output or splanchnic circulation.

PMID- 11569486
TI  - Evaluation of AVL988/4 analyzer for measurement of ionized magnesium and ionized
      calcium.
AB  - Ionized magnesium (Mg++) and ionized calcium (Ca++) are the physiologically
      active forms of these elements in the body and their concentrations have clinical
      value. Though the AVL988/4 instrument that measures concentrations of Mg++ and
      Ca++ has been evaluated, some clinically important parameters were unknown. In
      this study, we evaluated AVL988/4 analyzer for measuring Mg++ and Ca++
      concentrations and provided the following information: (1) The newly formulated
      Becton Dickinson (BD) Vacutainer plastic tubes with clot activator and silicone
      as the stopper lubricant (serial no. 367820) caused a significant high bias for
      the Mg++ measurement but had no effect on the Ca++ measurement; (2) the optimal
      conditions for specimen storage were no exposure to air at 4 degrees C for up to
      24 h; (3) no significant difference in the results of the Ca++ concentration
      determined using AVL988/4 or i-STAT; (4) no carryover between samples was found.

PMID- 11569487
TI  - Rapid suppression of S-PTH by oral calcitriol and calcium in healthy
      premenopausal women.
AB  - The influence of oral calcium +/- cholecalciferol or calcitriol on S-PTH and
      whole blood ionized calcium (B-Ca++) in the very short term has not been
      elucidated. B-Ca++ and S-PTH were measured after overnight fast every 5 or 15 min
      for 4-h in 7 healthy premenopausal women (30-45 years) in a crossover design
      where the subjects were studied on 4 different days. Study 1: (control), 125-ml
      tap water (also given in studies 2-4); study 2: 1000 mg calcium, as calcium
      carbonate; study 3: 1000 mg calcium and 400 IU (5 microg) cholecalciferol; and
      study 4: 0.5 microg calcitriol plus 1000 mg calcium. Calcium plus 1,25(OH)2
      vitamin D3 induced a rapid and significant fall in S-PTH compared to the control
      period (p < 0.02). Calcium alone or calcium plus cholecalciferol did not change
      the PTH levels significantly compared to control (water). B-Ca++ increased
      significantly after calcium plus 1,25(OH)2 vitamin D3 (p<0.01) and calcium plus
      cholecalciferol (p<0.05) compared to the control period. The B-Ca++ elevation was
      significantly higher after calcium plus 1,25 vitamin D3 than after calcium plus
      cholecalciferol (p<0.05). In conclusion, oral calcitriol plus calcium causes a
      rapid elevation in B-Ca++ and suppression of the PTH secretion also in the short
      term (hours).

PMID- 11569488
TI  - Moderate alcohol consumption and urinary excretion of magnesium and calcium.
AB  - The aim of this study was to evaluate the magnesium (Mg) status of male subjects
      consuming moderate amounts of alcohol (n = 14) in comparison with that of a group
      of non-consumers of alcohol (n = 10). Plasma ionized Mg levels and total
      erythrocyte Mg content were determined as well as the excretion of Mg in urine
      before and after an oral loading test. Intake of Mg via food and water was
      estimated using a one-week dietary records. The results showed a significantly
      higher, alcohol dose-related excretion of Mg and Ca (calcium) in the urine after
      the oral Mg load among consumers of alcohol. Although the study is based on a
      small number of subjects with differences in smoking habits, it is suggested that
      alcohol consumption even in moderate amounts could contribute to Mg deficiency.

PMID- 11569489
TI  - Novel plasma extraction procedure and development of a specific enzyme
      immunoassay of oxytocin: application to clinical and biological investigations of
      small cell carcinoma of the lung.
AB  - Paraneoplastic secretion of the lactation-inducing hormone oxytocin (OT) has been
      reported in about 30% of cases of small cell carcinoma of the lung (SCCL). In
      order to investigate the role of OT in the biology of SCCL tumours, a specific
      enzyme-immunoassay (EIA) for OT, which can be applied to both human plasma and
      culture medium, has been developed. OT EIA is performed on 96-well microtiter
      plates coated with a rabbit polyclonal antibody (Ab) anti-OT (04). This antibody
      does not exhibit any significant cross-reactivity either with vasopressin (VP) or
      with vasotocin (VT). The immunological reaction involving Ab anti-OT is a
      competition between the tracer (biotinylated OT) and synthetic OT (standard
      curve) or OT present in biological samples. In order to limit interference
      induced by plasma proteins, plasma samples are filtrated by a one-step
      centrifugation on centricon YM-3 (cut-off 3000 Da). After plasma filtration, 90.7
      +/- 5.1 (SD) % (n = 22) immunoreactive (IR) OT is recovered. The sensitivity of
      OT EIA is 1 pmol/L, while intra- and inter-assay coefficients of variation (CV)
      are around 3.41% and 2.84%, respectively. In healthy volunteers, plasma IR OT is
      7.28 +/- 4.49 (SD) pmol/L (n = 32) with no gender difference. As shown by the
      data both from plasma of SCCL patients and from supernatants and cell contents of
      SCCL cell lines, this EIA procedure offers a novel, reproducible, specific and
      sensitive method for the measurement of IR OT.

PMID- 11569490
TI  - Usefulness of helical computed tomography in the identification of the initial
      course of coronary anomalies.

PMID- 11569491
TI  - Should we routinely measure lipoprotein(a) in postmenopausal African-American
      women?

PMID- 11569492
TI  - Rat aortic stenting: toward a simple model of in-stent restenosis.

PMID- 11569493
TI  - Loss of cardioprotective effects of preinfarction angina in elderly but not in
      adult patients.

PMID- 11569494
TI  - An obesity epidemic in modern China.

PMID- 11569495
TI  - Roots of clinical resistance to STI-571 cancer therapy.

PMID- 11569496
TI  - Elephant hunting and conservation.

PMID- 11569497
TI  - The fourth dimension in cellular signaling.

PMID- 11569498
TI  - A synthetic theory of molecular evolution.
AB  - According to the neo-Darwinian view of evolution evolution rate nu depends solely
      on the environment variation rate gamma, whereas in the non-Darwinian view
      evolution rate is determined mainly by the mutation rate mu. We have studied two
      kinds of population genetics models which exhibit both types of evolution in
      different parametric regions: one is a dynamical model representing infinite
      population, and the other is a Markov process model representing a nearly
      monomorphic finite population. In the infinite population model, after proving
      general time-derivative and mu-derivative formulas for the population average of
      quantitative traits, we show that if the mutation rate is adaptively determined,
      mu must be larger than nu in the stationary state. Loads of evolution are
      obtained in both regions. A high evolution rate such as nu = 1 per genome per
      generation is consistent with Haldane's value of tolerable load if and only if
      the functional constraint is not large and selection is weak, independent of
      whether the evolution is neo-Darwinian or non-Darwinian. As the selection
      intensity increases, nu is shown to change discontinuously from nearly mu to
      gamma at the transition point. In the finite population model, the transition of
      v is not discontinuous, but is very steep. On the other hand, no steep change of
      polymorphism takes place at the transition point. The steepness of the transition
      in our model suggests that real molecular evolution can be divided into either
      neo-Darwinian or non-Darwinian,and that the intermediate type of evolution is
      rather rare.

PMID- 11569499
TI  - Comparison of DNA and protein polymorphisms between humans and chimpanzees.
AB  - To examine the nucleotide diversity at silent (synonymous + intron +
      untranslated) and non-silent (nonsynonymous) sites in chimpanzees and humans,
      genes at six nuclear loci from two chimpanzees were sequenced. The average silent
      diversity was 0.19%, which was significantly higher than that in humans (0.05%).
      This observation suggests a significantly larger effective population size and a
      higher extent of neutral polymorphism in chimpanzees than in humans. On the other
      hand, the non-silent nucleotide diversity is similar in both species, resulting
      in a larger fraction of neutral mutations at non-silent sites in humans than in
      chimpanzees. Other types of polymorphism data were collected from the literature
      or databases to examine whether or not they are consistent with the nuclear DNA
      sequence polymorphism observed here. The nucleotide diversity at both silent and
      non-silent sites in mitochondrial (mt) DNA genes was compatible with that of the
      nuclear genes. Microsatellite loci showed a similar high extent of heterozygosity
      in both species, perhaps due to the combined effect of a high mutation rate and a
      recent population expansion in humans. At protein loci, humans are more
      heterozygous than chimpanzees, and the estimated fraction of neutral alleles in
      humans (0.84) is much larger than that in chimpanzees (0.26). These data show
      that the neutral fraction in non-silent changes is relatively large in the human
      population. This difference may be due to a relaxation of the functional
      constraint against proteins in the human lineage. To evaluate this possibility,
      it will be necessary to examine nucleotide sequences in relation to the
      physiological or biochemical properties of proteins.

PMID- 11569500
TI  - Identification and structural analysis of SINE elements in the Arabidopsis
      thaliana genome.
AB  - An insertion sequence was found in a Mu homologue in the genome of Arabidopsis
      thaliana. The insertion sequence had poly(A) at the 3' end, and promoter motifs
      (A- and B-boxes) recognized by RNA polymerase III. The sequence was flanked by
      direct repeats of a 15-bp sequence of the Mu homologue, which appears to be a
      target-site sequence duplicated upon insertion. These findings indicate that the
      insertion sequence is a retroposon SINE, and it was therefore named AtSN (A.
      thaliana SINE). Many members of the AtSN family were identified through a
      computer-aided homology search of databases and classified into two subfamilies,
      AtSN1 and AtSN2, having consensus sequences 159 and 149 bp in length,
      respectively. These had no homology to SINEs in other organisms. About half of
      AtSN members were truncated through loss of a region at either end of the
      element. Most of them were truncated at the 5' end, and had a duplication of the
      target-site sequence. This suggests that the ones with 5' truncation retroposed
      by the same mechanism as those without truncation. Members of the AtSN1 or AtSN2
      subfamilies had many base substitutions when compared with the consensus
      sequence. All of the members examined were present in three different ecotypes of
      A. thaliana (Columbia, Landsberg erecta, and Wassilewskija). These findings
      suggest that AtSN members had proliferatedbefore the A. thaliana ecotype strains
      diverged.

PMID- 11569501
TI  - Identity of Cypripedium calceolus (Orchidaceae) in Rebun Island: comparative DNA
      analysis of related species.
AB  - Cypripedium calceolus was found in 1980 in Rebun Island off the north coast of
      Hokkaido, Japan, but the origin of this plant has been a controversial issue. In
      this study, we have made a comparative study by chloroplast DNA sequencing
      analysis among C. calceolus which occurs in Rebun Island and populations of C.
      calceolus from western Europe, China and far eastern Russia (Nakhodka), and also
      as references, C. macranthos in Japan and other Cypripedium species in North
      America. A Cypripedium cf. "calceolus", found recently in eastern Hokkaido, was
      also included in this analysis. The C. calceolus samples analyzed were
      categorized into three groups, i.e., those from Western Europe, from China and
      far eastern Russia, and from Rebun Island. The C. calceolus in Rebun Island was
      clearly different from the others in terms of DNA sequence and morphological
      features. The C. cf. calceolus from eastern Hokkaido and one sample from
      Nadhodka, Russia, were also classified into the same group as those from Rebun
      Island, although some differences in their morphological features were observed.
      It is concluded that the C. calceolus found in Rebun Island is not identical with
      those growing in Europe and China. In addition, it was found that it may be
      possible to classify C. macranthos into two groups, namely groups which include
      or do not include var. rebunense. An unidentified Cypripedium species found in
      Rebun Island falls into the same group as var. rebunense.

PMID- 11569502
TI  - Identification of a monofunctional aspartate kinase gene of Arabidopsis thaliana
      with spatially and temporally regulated expression.
AB  - We screened a gene trap library of Arabidopsis thaliana and isolated a line in
      which a gene encoding a homologue of monofunctional aspartate kinase was trapped
      by the reporter gene. Aspartate kinase (AK) is a key enzyme in the biosynthsis of
      aspartate family amino acids such as lysine, threonine, isoleucine, and
      methionine. In plants, two types of AK are known: one is AK which is sensitive to
      feedback inhibition by threonine and carries both AK and homoserine dehydrogenase
      (HSD) activities. The other one is monofunctional, sensitive to lysine and
      synergistically S-adenosylmethionine, and has only AK activity. We concluded that
      the trapped gene encoded a monofunctional aspartate kinase and designated as AK
      lys3, because it lacked the HSD domain and had an amino acid sequence highly
      similar to those of the monofunctional aspartate kinases ofA. thaliana. AK-lys3
      was highly expressed in xylem of leaves and hypocotyls and stele of roots.
      Significant expression of this gene was also observed in trichomes after bolting.
      Slight expression of AK-lys3 was detected in vascular bundles and mesophyll cells
      of cauline leaves, inflorescence stems, sepals, petals, and stigmas. These
      results indicated that this aspartate kinase gene was not expressed uniformly but
      in a spatially specific manner.

PMID- 11569503
TI  - Further yearly analyses of spontaneous pink mutant events in the stamen hairs of
      tradescantia clone BNL 4430 cultivated in the NSC growth chamber.
AB  - In order to confirm the results obtained in the previous 1-year-term (December
      12, 1998, through December 10, 1999) scorings and analyses of spontaneous pink
      mutant events (PMEs) in the stamen hairs of Tradescantia clone BNL 4430
      cultivated in a nutrient solution circulating (NSC) growth chamber, similar
      scorings and analyses were continued for another 52-week period from December 11,
      1999, through December 8, 2000. The environmental conditions were not changed,
      except for a minor modification in the method of supplying the nutrient solution
      used. During the scoring period, 732,128 stamen hairs with an average cell number
      of 24.90 cells were observed, and 2,368 PMEs were detected. The overall
      spontaneous somatic mutation frequency was 1.35 +/- 0.03 PMEs per 10(4) hair-cell
      divisions, which was significantly lower than the value of 1.56 +/- 0.03
      determined in the previous 52-week period, and the frequencies were lower during
      April through September than in other months, the period showing lower
      frequencies lasting 1-month longer than in the previous year. The present results
      reconfirmed the occurrence of a clear seasonal variation in the spontaneous
      mutation frequency in the NSC growth chamber, and the lower overall frequency,
      probably related to the minor modification in supplying the nutrient solution, is
      helpful for conducting mutagenicity tests at low levels, offering a lower
      background level. The analyses of the sectoring patterns of all these PMEs showed
      that the most of the 203 cases of multiple (two to five) pink sectors observed in
      the same stamen hairs (scored as 253 PMEs for calculating mutation frequency)
      were the results of events involving somatic recombinations occurred in single
      cells or cell lineages, rather than those of two or more independent somatic
      mutations occurred in different cells, agreeing with our previous study, and the
      significance of somatic recombinations in causing single PMEs was also
      reconfirmed.

PMID- 11569504
TI  - A statistical analysis of nucleotide substitutions in the Drosophila Adh region
      reflects irregularities in molecular clocks.
AB  - Substitutions rates are expected to be rather constant when a gene is compared
      between species. To analyze this feature, Ka/Ks ratios have been studied for
      Alcohol dehydrogenase (Adh) and Alcohol dehydrogenase duplication (Adh-dup) genes
      in Drosophila species. Adh Ka/Ks values are lower in intrasubgenus comparisons
      involving species of the Sophophora group than when these species are compared to
      the D. immigrans and S. lebanonensis, and this difference does not occur in the
      Adh-dup comparisons.

PMID- 11569505
TI  - Lateral approach to laparoscopic cholecystectomy in the previously operated
      abdomen.
AB  - BACKGROUND: In the past, prior abdominal surgery was often felt to be a
      contraindication to laparoscopic cholecystectomy. The presence of adhesions
      precludes using a simple paraumbilical open approach for insufflation and initial
      trocar insertion because of an increased risk of bowel perforation and the
      difficulty in obtaining adequate exposure. PATIENTS AND METHODS: We report 32
      consecutive patients with previous upper midline incisions who underwent
      laparoscopic cholecystectomy with cholangiography and describe the technique and
      lateral positioning to facilitate this approach. RESULTS: In our series, there
      were no complications. The mean length of hospital stay was 1.3 days, and the
      conversion rate to an open procedure was 3%: one patient who had had 22 previous
      abdominal operations. CONCLUSION: Laparoscopic cholecystectomy performed with the
      patient in the lateral position is safe and effective for patients who have had
      previous midline incisions.

PMID- 11569506
TI  - How do bile duct injuries sustained during laparoscopic cholecystectomy differ
      from those during open cholecystectomy?
AB  - BACKGROUND AND PURPOSE: Bile duct injuries sustained during laparoscopic
      cholecystectomy differ from those of open cholecystectomy. The authors conducted
      a retrospective analysis of their experience with 124 major bile duct injuries to
      identify these differences. PATIENTS AND METHODS: Biliary injury in 83 patients
      (67%) was sustained during open cholecystectomy, while in 41 patients (33%), it
      occurred during laparoscopic cholecystectomy. Intraoperative recognition was
      possible in 21 patients (25%) in the former group and in 14 patients (34%) in the
      latter (P < 0.05). RESULTS: The median time of presentation after laparoscopic
      cholecystectomy was 37 days v 240 days after open cholecystectomy (P < 0.001).
      Twenty-eight patients presented with external biliary fistulae in both groups.
      Spontaneous closure of these fistulae occurred in 21 patients (75%) in the open
      cholecystectomy group and in only 10 patients (36%) in the laparoscopic group (P
      < 0.01). Bismuth type III or IV injuries were the commonest type in the
      laparoscopic cholecystectomy group (N = 25; 61%) while Bismuth type I or II were
      the usual injuries in open cholecystectomy (N = 57; 69%) (P < 0.01). After
      hepaticojejunostomy, over a mean follow-up period of 3.4 years, stenosis of the
      hepaticojejunostomy was seen in two patients in both groups. CONCLUSION: Compared
      with open cholecystectomy, biliary injuries sustained during laparoscopic
      cholecystectomy are more likely to present earlier, are more often associated
      with persistent bile leaks, and are usually high injuries. However, the results
      of surgical repair do not appear to be different in these two groups.

PMID- 11569507
TI  - Role of intraoperative insulin monitoring in surgical management of insulinoma.
AB  - BACKGROUND AND PURPOSE: Precise localization and surgical excision is the
      therapeutic strategy for insulinomas. However, it is often difficult to localize
      the insulinomas, because of their small size. Surgeons may not localize and
      remove all of them together, particularly in patients with multiple insulinomas.
      We reviewed our experience to confirm the efficacy of blood glucose and
      intraoperative immunoreactive insulin (IRI) monitoring for surgical management of
      insulinomas. PATIENTS AND METHODS: Thirty-nine patients with insulinoma were
      surgically treated in our department. Perioperative blood glucose monitoring was
      performed in 14 patients, intraoperative quick IRI assay of the peripheral blood
      in 10 patients, and assay of a portal sample in 4 patients by an IMX analyzer.
      RESULTS: Rebound response of blood glucose to insulinoma removal was not always
      noted (8/14; 57%). Seven of ten patients showed a decrease of peripheral serum
      IRI levels within 15 minutes after removal of the insulinoma. The other two
      patients showed a rebound response of peripheral blood glucose or portal IRI. All
      the patients who had intraoperative monitoring of peripheral blood and peripheral
      and portal IRI had no recurrent insulinoma syndrome after surgical removal of
      their insulinomas. CONCLUSION: Combined monitoring of peripheral blood glucose
      and peripheral and portal IRI are helpful in the surgical management of
      insulinomas, as they can indicate that no insulinoma remains.

PMID- 11569508
TI  - Laparoscopic intragastric stapled cystogastrostomy for pancreatic pseudocyst.
AB  - BACKGROUND: Mature symptomatic pancreatic pseudocysts require surgical
      intervention for their management. In this era of minimal access surgery, several
      reports are now available of laparoscopic management of pancreatic pseudocysts.
      PATIENTS AND METHODS: We have performed this procedure in five patients over the
      past 2 years. Four patients developed the pseudocyst after acute alcoholic
      pancreatitis and one following acute biliary pancreatitis. The diameter of the
      pseudocyst ranged from 8 to 12 cm. The procedure was performed using five ports.
      The Harmonic Scalpel was used to create two ports in the anterior stomach wall
      through which two balloon trocars were placed into the gastric lumen. Following
      balloon inflation, the trocars were used to lift up the anterior gastric wall.
      This created the space for the cystogastrostomy to be fashioned laparoscopically
      through the balloon trocar. The ball probe of the Harmonic Scalpel was used to
      puncture the cyst through the posterior gastric wall. The cystogastrostomy was
      completed by firing an Endo-GIA30 stapler across the fused posterior gastric wall
      and anterior wall of the cyst. RESULTS: The mean operative time was 90 minutes
      (range 80-125 minutes). The mean postoperative stay was 3.0 days. One patient had
      intraoperative bleeding at the anastomotic site, which was easily controlled.
      CONCLUSION: Laparoscopic cystogastrostomy offers a feasible and safe therapeutic
      option for selected patients with large symptomatic pancreatic pseudocysts.

PMID- 11569509
TI  - Diagnostic laparoscopy decreases the rate of unnecessary laparotomies and reduces
      hospital costs in trauma patients.
AB  - BACKGROUND AND PURPOSE: The use of laparoscopy for the treatment of various
      surgical diseases has been well described, and recently, it has gained popularity
      in the evaluation of abdominal trauma patients. The value of diagnostic
      laparoscopy (DL) in avoiding unnecessary laparotomies and its effects on hospital
      costs was evaluated in a prospective clinical trial. PATIENTS AND METHODS: In a
      48-month period, 99 hemodynamically stable abdominal trauma patients (28 blunt
      and 71 penetrating injuries) among 428 patients admitted with abdominal trauma in
      whom the decision for surgical exploration was made were accepted for the study
      and underwent DL prior to laparotomy. RESULTS: The DL was negative in 60.7% of
      the patients with blunt abdominal trauma (BAT) and in 62.0% of the patients with
      penetrating abdominal trauma (PAT). Laparoscopy-positive patients (Group 1)
      underwent immediate laparotomy, whereas on DL-negative patients (Group 2), no
      laparotomies were performed. Hospitalization times and hospital costs of the two
      groups were recorded and compared. The difference between the hospitalization
      times of Group 1 and Group 2 was statistically significant (P < 0.001). The use
      of DL reduced the rate of unnecessary laparotomies from 60.7% to 0 in BAT and
      from 78.9% to 16.9% in PAT. The mean hospitalization time was 2.75 +/- 1.20 days
      in patients with negative DL, whereas it was 7.4 +/- 2.20 days and 5.2 +/- 1.42
      days in DL-positive patients undergoing a therapeutic and nontherapeutic
      laparotomy, respectively. When the hospital costs of the Group 1 patients were
      compared with those of Group 2 patients, there was a 4.07-fold increase in
      patients undergoing therapeutic laparotomy and a 1.78-fold increase in patients
      undergoing nontherapeutic laparotomy. CONCLUSION: Diagnostic laparoscopy might be
      used in selected patients to exclude significant intra-abdominal injuries.

PMID- 11569510
TI  - Laparoscopic telescope with alpha port and aesop to view open surgical
      procedures.
AB  - Laparoscopy has advanced surgery by allowing the surgeon to operate within a
      patient's abdominal and pelvic cavity with minimal trauma and scarring. The
      coupling of a video camera to the laparoscopic telescope has had the secondary
      effect of allowing others to view the surgical field either on color video
      monitors or by watching the video feed over the Internet at a remote location.
      These advancements have allowed better teaching and mentoring of operations. Open
      procedures can benefit from this technology as well but have suffered in the past
      from inadequate methods to depict the open surgical field. We used the Alpha Port
      and Aesop robot to position a sterile laparoscopic telescope near the surgical
      field to view open cholecystectomies performed on five pigs and to send the video
      feed over the Internet to remote physicians. Viewing the video on the monitor,
      the surgeons performed the operation in a comfortable ergonomic upright position.
      Both the surgeons and the remote physicians found the quality of the video to be
      excellent, and the remote physicians felt comfortable learning and mentoring
      surgical procedures using this technique.

PMID- 11569511
TI  - Laparoscopic extended cholecystectomy.
AB  - BACKGROUND: Inadvertent dissemination of latent gallbladder (GB) cancer has
      become a crucial issue with the widespread use of laparoscopic cholecystectomy as
      a standard operation for benign gallbladder diseases. METHODS: Laparoscopic
      extended cholecystectomy is a new technique we have developed for the resection
      of GB tumors with suspicion of malignancy. The procedure is safe and minimally
      invasive and prevents tumor dissemination. The GB is resected laparoscopically
      along with a 1-cm margin of the liver using LaparoSonic Coagulating Shears
      without any ligation or clipping. RESULTS: We applied this technique to a patient
      with a GB tumor in the fundus. The tumor was not exposed on the cut surface, and
      there were no postoperative complications. CONCLUSION: Laparoscopic extended
      cholecystectomy for GB tumors with suspicion of malignancy is a minimally
      invasive technique that may decrease the risk of tumor dissemination.

PMID- 11569512
TI  - Laparoscopic aortorenal bypass using a PTFE graft: survival study in the porcine
      model.
AB  - PURPOSE: To verify the technical feasibility of laparoscopic aortorenal bypass in
      a porcine model and to evaluate renal pathologic findings after a short survival
      time. MATERIALS AND METHODS: Laparoscopic aorta-to-left-renal artery bypass using
      an interposition Gore-Tex graft was performed in five animals. Renal function was
      assessed 1 week postoperatively and euthanasia performed after 14 days for
      histologic examination. RESULTS: The median surgical time was 210 minutes (range
      160-260 minutes). The median time needed to perform the aorta-to-graft
      anastomosis was 65 minutes (range 50-75 minutes), and the median time required to
      create the graft-to-renal artery anastomosis was 50 minutes (range 45-60
      minutes). No conversion to open surgery was needed. Two intraoperative
      complications were observed: one large-bowel perforation, which was managed
      laparoscopically, and one obstruction of the aorta-to-graft anastomosis caused by
      clots, which was managed by removal of clots with a balloon catheter. No major
      postoperative complications were observed. The mean preoperative and
      postoperative serum creatinine concentrations were 0.8 +/- 1.2 and 0.7 +/- 1.6
      mg/dL, respectively. At autopsy, all but one of the pigs were found to have a
      patent aortorenal bypass. In one pig, we found a partially clotted graft.
      Histologic examination demonstrated an unremarkable kidney in four cases and a
      kidney showing aspects of coagulative necrosis with viable cells in the animal
      with the partially clotted graft. CONCLUSIONS: Laparoscopic aortorenal bypass is
      feasible. The short-term effect of the bypass on kidney vascularization seems
      promising, as demonstrated by pathologic findings. Laparoscopic aortorenal bypass
      could extend the indications for renal revascularization surgery.

PMID- 11569513
TI  - Laparoscopic cholecystectomy in situs inversus totalis: is it safe?
AB  - A 46-year-old woman with known situs inversus totalis and recent mitral valve
      replacement presented with nausea and vomiting. Ultrasonography demonstrated a
      left-sided microlithiasic gall-bladder. Laparoscopic cholecystectomy was
      performed successfully. The postoperative recovery was uneventful. The literature
      on this subject is reviewed.

PMID- 11569514
TI  - Feasibility of laparoscopic cholecystectomy in situs inversus.
AB  - PURPOSE: To address the feasibility and safety of laparoscopic cholecystectomy in
      situs inversus and highlight the necessary modifications in the surgical
      technique. PATIENTS AND METHODS: We present our experience in two patients with
      situs inversus and symptomatic gallstones who were treated successfully by
      laparoscopic cholecystectomy. The surgeon stood on the right side with the video
      monitor above the patient's left shoulder. Two 10-mm ports were placed in the
      epigastric and subumbilical positions. Two 5-mm ports were placed in the left mid
      clavicular and left anterior axillary lines. The two procedures were carried out
      uneventfully after reorientation of the visual-motor skills of the surgeon and
      cameraman to the left upper quadrant. A summary of a further similar 13 cases so
      far treated in the English-language medical literature is also presented.
      RESULTS: Skeletonizing the structures in Calot's triangle consumed extra time and
      was more difficult than in patients with a normally sited gallbladder. However,
      the hospital stay and postoperative complications were similar. CONCLUSION:
      Laparoscopic cholecystectomy in situs inversus seems to be feasible and safe
      provided it is performed by an expert laparoscopic surgeon who takes time in
      clearly demonstrating the extrahepatic mirror image anatomy of the biliary tree
      with its right-to-left shift.

PMID- 11569515
TI  - Laparoscopic cholecystectomy in a patient with situs inversus totalis.
AB  - Situs inversus is a rare anomaly characterized by transposition of organs to the
      opposite side of the body. In this group of patients, cholelithiasis is observed
      with a frequency similar to the normal population. Herein, we report a patient
      with situs inversus totalis who underwent a successful laparoscopic
      cholecystectomy. Diagnostic pitfalls and technical details of the operation are
      discussed in the context of the available literature.

PMID- 11569516
TI  - Laparoscopic marsupialization and hemisplenectomy for splenic cysts.
AB  - BACKGROUND: Splenic cysts are a rare clinical entity in the United States, and
      historically, management has consisted of either partial or total splenectomy via
      an open approach. Laparoscopic treatment of splenic cysts with preservation of
      splenic parenchyma offers several advantages. Compared with the open approach, a
      laparoscopic approach may result in less postoperative pain and a more rapid
      return to full activity. Compared with total splenectomy, splenic preservation
      eliminates the risk of overwhelming postsplenectomy infection. PATIENTS AND
      METHODS: We present two patients with splenic cysts. One patient was treated with
      laparoscopic marsupialization of the cyst and the other with laparoscopic
      hemisplenectomy. RESULTS: Both patients are without further symptoms at 26 and 5
      months' follow-up, respectively. CONCLUSIONS: Laparoscopic marsupialization and
      hemisplenectomy are appropriate treatment options for patients with splenic
      cysts.

PMID- 11569517
TI  - Computer-assisted robotic heller myotomy: initial case report.
AB  - PURPOSE: Our objective was to determine the efficacy of computer-assisted robotic
      laparoscopic Heller myotomy. METHODS: A 76-year-old woman with a significant
      history of achalasia was evaluated for laparoscopic Heller myotomy. The daVinci
      surgical system was used throughout the procedure. RESULTS: Computer assistance
      allowed scaling of hand motions from a range of 2:1 to 5:1. Successful dissection
      of the esophageal musculature was accomplished, and a Toupet-type fundoplication
      was performed. The patient was discharged from the hospital the day after surgery
      with five port incisions, each <1 cm. CONCLUSIONS: Telemanipulator computer
      assisted surgical devices may have applications in procedures that require
      advanced and finely tuned motions, such as Heller myotomy. The benefits of extra
      magnification and three-dimensional imaging can help prevent esophageal
      perforation and identify residual circular muscle fibers.

PMID- 11569518
TI  - Laparoscopic appendectomy for Crohn's disease of the appendix presenting as acute
      appendicitis.
AB  - BACKGROUND: Crohn's disease confined to the appendix is rare but has been well
      described in the literature. It can mimic acute appendicitis clinically. After
      surgical treatment, recurrences of Crohn's disease are rare. We report the first
      case of treatment by laparoscopic appendectomy of Crohn's disease confined to the
      appendix. METHODS: A healthy 32-year old man presented with a week-long history
      of vague lower abdominal pain. Diagnostic work-up, which included CT,
      enteroclysis, and routine blood work, revealed a patent appendiceal lumen with an
      inflammatory mass in the right lower quadrant. RESULTS: Diagnostic laparoscopy
      revealed an inflamed appendix, and a laparoscopic appendectomy was performed,
      with frozen-section examination revealing Crohn's disease of the appendix. Two
      years after surgery, the patient has not had a recurrence of symptoms.
      CONCLUSIONS: Crohn's disease of the appendix can mimic acute appendicitis,
      although often with a more indolent course. The disease may be treated
      successfully by laparoscopic appendectomy, with good long-term results.

PMID- 11569519
TI  - Blunt hasson trocar injury: long intra-abdominal trocar and lean patient--a
      dangerous combination.
AB  - Injury at the time of trocar placement with the Hasson approach is rare. The cone
      of the Hasson cannula is wedged into the skin for an air seal, and, using fascial
      sutures, fastened under tension to flanges of the cannula. The shorter the
      fascial securing suture, the greater the tension and the more secure the air
      seal. Flanges for securing the fascial suture were attached to the external
      cannula in early Hasson cannula models. With these, much of the trocar needs to
      be intra-abdominal in order to shorten the suture. For lean patients, with very
      little distance between the anterior and posterior abdominal walls, the force
      required to fasten the sutures to the flanges may allow an intra-abdominal trocar
      to damage intervening organs. Later versions of the cannula had the flanges
      attached to the cone, allowing for short suture without need for intra-abdominal
      cannula. These models avoid the possibility of such injury. An unusually lean
      patient underwent laparoscopic cholecystectomy using an older Hasson cannula with
      flanges for the fascial securing suture attached to the cannula. Postoperative
      changes in vital signs and hemoglobin led to a diagnosis of intra-abdominal
      bleeding, and laparotomy revealed a transsected branch of the middle colic
      artery. Earlier Hasson cannulas, where the flanges are attached to the cannula,
      should be replaced with those with flanges attached to the cone.

PMID- 11569520
TI  - Literature watch.

PMID- 11569521
TI  - The drug metabolism discussion group in 2001.

PMID- 11569522
TI  - The long, hard road: drug metabolism in the lifetime of the DMDG.

PMID- 11569523
TI  - Role of transport proteins in drug absorption, distribution and excretion.
AB  - 1. The molecular and functional characterization of transport proteins is
      emerging rapidly and significant numbers of drugs have been shown to be
      substrates or inhibitors. The purpose of this review is to highlight the in vivo
      preclinical and clinical evidence that supports a role for transport proteins in
      attenuating the absorption, distribution and excretion (ADE) of drugs. 2. For
      absorption, a clear role has emerged for P-glycoprotein in limiting permeability
      across the gastrointestinal tract. As a result, a wide variety of drugs suffer
      from incomplete, variable and non-linear absorption. Similarly, at the blood
      brain barrier a range of drugs has limited brain penetration due to P
      glycoprotein-mediated efflux, which can limit therapeutic effectiveness of CNS
      agents. In the liver, transport proteins are present on the sinusoidal membrane
      that can be the rate-limiting step in hepatic clearance for some drugs.
      Mechanistic studies clearly suggest a key role and broad substrate specificity
      for the OATP family of sinusoidal transporters. Mainly ATP-dependent transport
      proteins such as P-glycoprotein and MRP2 govern active biliary excretion. 3. Drug
      drug interactions have been demonstrated involving inhibition or induction of
      transport proteins. Clinically significant interactions in the gastrointestinal
      tract and kidney have been observed with inhibitors such as ketoconazole,
      erythromycin, verapamil, quinidine, probenecid and cimetidine. Clinically
      significant inhibition at the blood-brain barrier is more difficult to
      demonstrate, relying on pharmacodynamic and toxicodynamic changes, but an example
      is quinidine increasing loperamide-induced central effects in humans. 4. This
      review highlights the emerging role of transport proteins in ADE of drugs and
      suggests these need to be considered, in drug discovery and development, with
      respect to variability in drug disposition and response.

PMID- 11569524
TI  - Assessment of drug-drug interactions: concepts and approaches.
AB  - 1. A priori knowledge of the enzyme inhibitory potential of new drug entities and
      the drug-metabolizing enzymes involved can be used in support of important
      decisions on the future progress of a drug in clinical development. 2. Important
      advances in the knowledge of human drug-metabolizing enzymes have largely fuelled
      the integration of in vitro drug metabolism and clinical drug interaction studies
      for use in drug development programmes. 3. The likelihood of correctly predicting
      in vivo drug-drug interactions appears highly dependent on selecting the correct
      enzyme inhibition model for use in deriving the inhibitor constant (Ki) and
      correctly determining the available concentration of inhibitor at the active site
      of the enzyme(s) of interest. 4. The uncertainty and inaccuracy of predicting the
      extent and duration of in vivo drug interactions currently stems from a lack of
      definitive models by which to assess likely substrate and inhibitor
      concentrations at the active site of metabolism. Additional issues contributing
      to the uncertainty of predicting drug interactions include assumptions of the
      contribution of presystemic drug extraction and the effect of inhibitors on the
      processes involved. 5. This review considers the practical aspects of in vitro
      enzyme inhibition studies and the use of in vitro-in vivo correlation approaches
      described in the literature to predict in vivo drug-drug interactions.

PMID- 11569525
TI  - Implications and consequences of enzyme induction on preclinical and clinical
      drug development.
AB  - 1. Enzyme induction has traditionally been studied during drug development to
      assess the potential of drug entities to interact with concomitant medications
      and alter their pharmacological effects, and clearly it is an unwanted
      phenomenon. However, another hurdle caused by induction occurs during preclinical
      development via the attainment of safety data, obtained by dosing high quantities
      of compound to species used in toxicology assessment. This review considers the
      techniques that can now be utilized in drug discovery, their relevance, the
      pharmacokinetic aspects of this phenomenon, and it discusses the consequences and
      implications of induction during preclinical and clinical development. 2. It is
      becoming increasingly routine to employ hepatocyte cultures and novel techniques
      such as quantitative real-time reverse transcriptase PCR to identify enzyme
      inducers in vitro. The major challenge is to utilize these in vitro data to
      predict the consequences of induction in vivo. From an understanding of
      pharmacokinetic principles and low clinical doses relative to preclinical
      studies, there is limited potential for induction by a development candidate to
      significantly alter the pharmacological efficacy of a co-administered drug. 3.
      The most comprehensive approach when considering induction involves integrating
      quantitative in vitro data, information on the pharmacokinetic behaviour of the
      compound and the PK/PD) relationship in order to predict its consequences. The
      generation of this holistic strategy would enable more detailed and informed
      decision-making about both the suitability of molecules for development and the
      development strategy itself.

PMID- 11569526
TI  - High-throughput screening approaches for investigating drug metabolism and
      pharmacokinetics.
AB  - 1. High-throughput screening approaches have been adopted throughout the
      pharmaceutical industry to aid in the rapid discovery of new chemical entities.
      Because it is now well recognized that the selection of a robust candidate
      requires a balance of potency, safety and pharmacokinetics, the role of drug
      metabolism departments has widened from their traditional one of supporting drug
      development to include the screening of compounds during the discovery process.
      To put drug metabolism and pharmacokinetic (DMPK) studies in context, the
      evolving role of DMPK screening in the drug discovery strategy of pharmaceutical
      companies will be discussed and a generalized approach will be presented. 2. With
      the increasing numbers of compounds requiring screening, DMPK optimization
      methods have had to be adapted for high throughput. There have been many
      developments in this field over the past decade and this review will focus on the
      high-throughput DMPK screening methodologies used today and in the recent past.
      3. In vitro and in silico (computer-based) methods have proven most amenable to
      high-throughput approaches and these will firm the bulk of the review, but some
      advances with in vivo methods will also be discussed. As there has been a vast
      increase in published material on the topic of high-throughput DMPK methodologies
      in the past 10 years, it would be impossible to cover every method in detail, so
      this review will concentrate on the key areas and refer the reader to other, more
      detailed reviews wherever possible. 4. Most high-throughput methods would not be
      possible without the enabling technologies of computing, automation, new sample
      preparation technologies, and highly sensitive and selective detection systems,
      and these will also be reviewed. 5. The advantages and disadvantages of the
      screening methods will be presented, in particular the issue of handling the
      false-positives and -negatives that arise. 6. In concluding the review, future
      developments in this field will be discussed along with key issues that will need
      to be addressed.

PMID- 11569527
TI  - Utility of metabolic stability screening: comparison of in vitro and in vivo
      clearance.
AB  - 1. The ability of hepatic microsomal metabolic stability assessments to predict
      in vivo clearance in rat has been retrospectively evaluated for 1,163 compounds
      from 48 programmes of chemistry. Using a simple binary classification system, the
      in vivo clearances of approximately 64% of the compounds were correctly
      classified. 2. About 24% of compounds were metalbolically stable yet had
      clearance greater than half of liver blood flow in vivo. This might be expected
      as microsomes only contain a limited number of fully functioning drug
      metabolizing enzymes and cannot be expected to account for extrahepatic or non
      metabolic clearance processes. 3. About 13% of compounds had in vivo clearances
      of less than half liver blood flow despite being classified as metabolically
      unstable. Despite overcoming metabolic instability, these compounds had other
      undesirable properties and were generally more highly bound to plasma proteins,
      had smaller volumes of distribution (and shorter half-lives despite their
      clearance) and were more inhibitory against the major human cytochrome P450s. 4.
      Taking plasma protein binding into consideration reduced the proportion of
      misclassified low-clearance compounds but did not improve the overall success
      appreciably. Somewhat surprisingly, human microsomes were nearly as effective as
      rat microsomes at classifying rat in vivo clearance.

PMID- 11569528
TI  - Quantitative analysis of pharmaceuticals in biological fluids using high
      performance liquid chromatography coupled to mass spectrometry: a review.
AB  - 1. The development of bio-analysis of drug molecules over the last 10 years is
      reviewed, focusing on advances in sample preparation, liquid chromatography and
      detection. 2. Developments have led to improvements in detection sensitivity,
      enhancements in specificity and increased capacity. 3. Emerging technologies such
      as monolithic column chromatography and miniaturized chip-based systems are
      discussed.

PMID- 11569529
TI  - Accelerator mass spectrometry (AMS): recent experience of its use in a clinical
      study and the potential future of the technique.
AB  - 1. The technique of accelerator mass spectrometry (AMS) is outlined. 2. The use
      of AMS in an initial validation study in animals is outlined. As part of the
      validation of the technique, samples from the animal study were analysed by both
      liquid scintillation counting (LSC) and, following dilution, by AMS. The results
      were similar. 3. The use of AMS in support of a clinical study is described. Six
      healthy male human volunteers were administered 2.7 mg [14C]-GI1817771 (121 Bq;
      3.3nCi) to produce an exposure to ionizing radiation of 0.06 microSv. Mass
      balance in recovery of administered radioactivity was achieved and information
      about the presence of systemically circulating metabolites was gained. 4. The
      future potential of the technique of AMS is discussed.

PMID- 11569530
TI  - Pharmacokinetic/pharmacodynamic assessment of the effects of E4031, cisapride,
      terfenadine and terodiline on monophasic action potential duration in dog.
AB  - 1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia
      associated with increases in QT interval and monophasic action potential duration
      (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the
      market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause
      TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds
      known to increase QT interval and cause TDP were investigated: terfenadine,
      terodiline, cisapride and E4031. On the basis that only free drug in the systemic
      circulation will elicit a pharmacological response target, free concentrations in
      plasma were selected to mimic the free drug exposures in man. Infusion regimens
      were designed that rapidly achieved and maintained target-free concentrations of
      these drugs in plasma and data on the relationship between free concentration and
      changes in MAPD were obtained for these compounds. 3. These data indicate that
      the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride
      (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man
      causing QT effects. For compounds that have shown TDP in the clinic (terfenadine,
      terodiline, cisapride) there is little differentiation between the dog ED50 and
      the efficacious free plasma concentrations in man (< 10-fold) reflecting their
      limited safety margins. These data underline the need to maximize the therapeutic
      ratio with respect to TDP in potential development candidates and the importance
      of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.

PMID- 11569531
TI  - Pharmacokinetics and metabolism of a selective PDE5 inhibitor (UK-343,664) in rat
      and dog.
AB  - 1. UK-343,664 is a novel potent and selective PDE5 inhibitor. Plasma clearances
      in the male and female rat were high (120 and 54 ml min(-1) kg(-1)), giving rise
      to short elimination half-lives (0.2 and 0.3h respectively). Lower clearance in
      dog (14 ml min(-1) kg(-1)) was the primary factor resulting in a longer
      elimination half-life (3.7 h). The higher clearance in rat than dog was in
      agreement with in vitro metabolism rates in hepatic microsomes. 2. The volume of
      distribution was lower in rat (1.3-2.11 kg(-1)) compared with dog (4.61 kg(-1))
      probably due to increased plasma protein binding in rat (96 versus 81% in dog).
      3. Oral bioavailabilities were 2, 12 and 70% in the male and female rat and dog
      respectively. Tmax < or = 0.5 h in all animals. 4. In multiple oral dose studies,
      increased systemic exposure was seen with increasing dose up to doses of 200 mg
      kg(-1) in rat and 150 mg kg(-1) in dog. A marked super-proportional increase in
      the male rat indicated a capacity-limited clearance at high doses. 5. At the
      maximal dose of 200 mg kg(-1) in the female rat, no clinical signs were observed
      after 14 days of treatment. Only minimal signs were recorded in the male rat and
      dog at the highest dose levels investigated. 6. After single oral or intravenous
      doses of [14C]-UK-343,664, the majority of radioactivity was excreted in the
      faeces of both species. 7. UK-343,664 was extensively metabolized in both rat and
      dog. The major primary pathways in dog involved piperazine N-deethylation and
      loss of a two carbon fragment from the piperazine ring (N,N'-de-ethylation). More
      extensive metabolism in the rat included additional notable metalbolites arising
      from hydroxylation and lactamization of the piperazine ring, which were only
      minor metabolites in the dog.

PMID- 11569532
TI  - Potential role for P-glycoprotein in the non-proportional pharmacokinetics of UK
      343,664 in man.
AB  - 1. UK-343,664 is a potent and specific PDE5 inhibitor. Following single oral
      doses to human volunteers, it exhibited non-proportional pharmacokinetics over
      the dose range 30-800 mg. Over this 27-fold dose range, Cmax and AUCt increased
      247- and 287-fold respectively. The half-life (4-6 h) was similar at all doses.
      No systemic exposure was quantifiable at doses <10 mg. 2. UK-343,664 is a
      lipophilic molecule (log D7.4 = 3.1) and as such is expected to be cleared mainly
      by metabolism. Based on studies with expressed human P450 enzymes it was
      concluded that the metabolism of UK-343,664 was predominantly mediated by CYP3A4.
      With a moderate Km = 76 microM for this enzyme, saturation of first-pass
      metabolism alone was considered unlikely to account for the non-proportional
      pharmacokinetics. 3. UK-343,664 showed high affinity for P-glycoprotein in vitro,
      with a Km = 7.3 microM. In transport studies in LLC-PK1 cell monolayers
      transfected with P-glycoprotein, UK343,664 showed marked polarized transport
      which was concentration dependent. 4. The high affinity of UK-343,664 for P
      glycoprotein is considered to be the primary source of the non-proportional
      pharmacokinetic profile observed in man.

PMID- 11569533
TI  - Pharmacokinetics of the novel, high-affinity and selective dopamine D3 receptor
      antagonist SB-277011 in rat, dog and monkey: in vitro/in vivo correlation and the
      role of aldehyde oxidase.
AB  - 1. In vitro studies with the selective dopamine D3 receptor antagonist SB-277011
      were conducted in liver microsomes and homogenates from rat, dog, cynomolgus
      monkey and human to correlate the rate of metabolism with the in vivo
      pharmacokinetics of the compound in rat, dog and cynomolgus monkey. 2. In the
      presence of NADPH, SB-277011 was relatively stable in the presence of liver
      microsomes from rat, dog, cynomolgus monkey and human with an intrinsic clearance
      (CLi) of < 2 ml min(-1) g(-1) liver for all species. In total liver homogenates,
      SB-277011 was metabolized at a similar rate in rat and dog (CLi < 2 ml min(-1) g(
      1) liver) to that in liver microsomes but in cynomolgus monkey and human (CLi =
      9.9 and 45 ml min(-1) g(-1) liver, respectively) the intrinsic clearance was
      approximately 6- and 35-fold higher, respectively, than that in liver microsomes.
      3. In the absence of NADPH, SR-277011 was rapidly cleared in liver homogenates
      from cynomolgus monkey and human (CLi = 7.4 and 27 ml min(-1) g(-1) liver,
      respectively) demonstrating that a significant pathway of metabolism of this
      compound was via an NADPH-independent non-microsomal oxidative route. This
      pathway was sensitive to inhibition with isovanillin suggesting that the enzyme
      responsible was aldehyde oxidase. 4. The in vivo pharmacokinetics showed that the
      plasma clearance of SB-277011 was low in rat (20 ml min(-1) kg(-1)), moderate in
      dog (14 ml min(-1) kg(-1)) and high in cynomolgus monkey (58 ml min(-1)kg(-1)),
      which is consistent with the in vitro findings and demonstrated a greater
      capacity for the monkey to metabolize this compound. The oral bioavailability of
      SB-277011 in rat, dog and cynomolgus monkey was 35, 43 and 2%, respectively.
      Given the high clearance of this compound in cynomolgus monkey, the low oral
      bioavailability is probably as a result of high first-pass elimination,
      specifically by aldehyde oxidase, rather than poor absorption. 5. The high in
      vitro clearance of SB-277011 in human liver homogenates and the involvement of
      aldehyde oxidase in the metabolism of SB-277011 indicates that the
      bioavailability of the compound is likely to be low in human.

PMID- 11569536
TI  - Cellular basis of steroid neuroprotection in the wobbler mouse, a genetic model
      of motoneuron disease.
AB  - 1. The Wobbler mouse suffers an autosomal recessive mutation producing severe
      motoneuron degeneration and astrogliosis in the spinal cord. It has been
      considered a suitable model of human motoneuron disease, including the sporadic
      form of amyotrophic lateral sclerosis (ALS). 2. Evidences exist demonstrating
      increased oxidative stress in the spinal cord of Wobbler mice, whereas
      antioxidant therapy delayed neurodegeneration and improved muscle trophism. 21
      Aminosteroids are glucocorticoid-derived hydrophobic compounds with antioxidant
      potency 3 times higher than vitamin E and 100 times higher than
      methylprednisolone. They do not bind to intracellular receptors, and prevent
      lipid peroxidation by insertion into membrane lipid bilayers. 3. In common with
      the spinal cord of ALS patients, Wobbler mice present astrocytosis with
      hyperexpression of glial fibrillary acidic protein (GFAP), and increased
      expression of nitric oxide synthase (NOS) and growth-associated protein (GAP-43)
      in motoneurons. Here, we review our studies on the effects of a 21-aminosteroid
      on GFAP, NOS, and GAP-43. 4. First, we showed that 21-aminosteroid treatment
      further increased GFAP-expressing astrocytes in gray matter of the Wobbler spinal
      cord. This effect may provide neuroprotection if one considers a trophic and
      beneficial function of astrocytes during the course of degeneration. Other
      neuroprotectans used in Wobbler mice (T-588) also increased pre-existing
      astrocytosis. 5. Second, histochemical determination of NADPH-diaphorase, a
      parameter indicative of neuronal NOS activity, showed that the 21-aminosteroid
      down-regulated the high activity of this enzyme in ventral horn motoneurons.
      Therefore, suppression of nitric oxide by decreasing NADPH-diaphorase (NOS)
      activity may provide neuroprotection considering that excess NO is highly toxic
      to motoneurons. 6. Finally, 21-aminosteroid treatment significantly attenuated
      the aberrant expression of both GAP-43 protein and mRNA in Wobbler motoneurons.
      Hyperexpression of GAP-43 possibly indicated abnormal synaptogenesis,
      denervation, and muscle atrophy, parameters which may return to normal following
      antioxidant steroid treatment. 7. Besides 21-aminosteroids, other steroids also
      behave as neuroprotectans. In this regard, degenerative diseases may constitute
      potential targets of these hormones, based on the fact that the spinal cord
      expresses in a regional and cell-specific fashion, receptors for androgens.
      progesterone, adrenal steroids, and estrogens.

PMID- 11569534
TI  - Mechanisms of amyloid beta protein-induced modification in ion transport systems:
      implications for neurodegenerative diseases.
AB  - 1. Alzheimer's disease (AD) is a neurodegenerative disorder that affects the
      cognitive function of the brain. Pathological changes in AD are characterized by
      the formation of amyloid plaques and neurofibrillary tangles as well as extensive
      neuronal loss. Abnormal proteolytic processing of amyloid precursor protein (APP)
      is the central step that leads to formation of amyloid plaque, neurofibrillary
      tangles, and neuronal loss. 2. The plaques, which accumulate extracellularly in
      the brain, are composed of aggregates and cause direct neurotoxic effects and/or
      increase neuronal vulnerability to excitotoxic insults. The aggregates consist of
      soluble pathologic amyloid beta peptides AbetaP[1-42] and AbetaP[1-43] and
      soluble nonpathologic AbetaP[1-40]. Both APP and AbetaP interact with ion
      transport systems. AbetaP induces a wide range of effects as the result of
      activating a cascade of mechanisms. 3. The major mechanisms proposed for AbetaP
      induced cytotoxicity involve the loss of Ca2+ homeostasis and the generation of
      reactive oxygen species (ROS). The changes in Ca2+ homeostasis could be the
      result of (1) changes in endogenous ion transport systems, e.g. Ca2+ and K+
      channels and Na+/K+-ATPase, and membrane receptor proteins, such as ligand-driven
      ion channels and G-protein-driven releases of second messengers, and (2)
      formation of heterogeneous ion channels. 4. The consequences of changes in Ca2+
      homeostasis-induced generation of ROS are (a) direct modification of intrinsic
      ion transport systems and their regulatory mechanisms, and (b) indirect effects
      on ion transport systems via peroxidation of phospholipids in the membrane,
      inhibition of phosphorylation, and reduction of ATP levels and cytoplasmic pH. 5.
      We propose that in AD, AbetaP with its different conformations alters cell
      regulation by modifying several ion transport systems and also by forming
      heterogeneous ion channels. The changes in membrane transport systems are
      proposed as early steps in impairing neuronal function preceding plaque
      formation. We conclude that these changes damage the membrane by compromising its
      integrity and increasing its ion permeability. This mechanism of membrane damage
      is not only central for AD but also may explain other malfunctioned protein
      processing-related pathologies.

PMID- 11569535
TI  - Is there a rationale for neuroprotection against dopamine toxicity in Parkinson's
      disease?
AB  - Parkinson's disease is a progressive neurological disease caused by rather
      selective degeneration of the dopaminergic neurons in the substantia nigra.
      Though subject to intensive research, the etiology of this nigral loss is still
      undetermined and treatment is basically symptomatic. The current major hypothesis
      is that nigral neuronal death in PD is due to excessive oxidative stress
      generated by auto and enzymatic oxidation of the endogenous neurotransmitter
      dopamine (DA), the formation of neuromelanin (NM) and the presence of a high
      concentration of iron. In this review article although we concisely describe the
      effects of NM and iron on neuronal survival, we mainly focus on the molecular
      mechanisms of DA-induced apoptosis. DA exerts its toxic effects through its
      oxidative metabolites either in vitro or in vivo The oxidative metabolites then
      activate a very intricate web of signals, which culminate in cell death. The
      signal transduction pathways and genes, which are associated with DA toxicity are
      described in detail.

PMID- 11569537
TI  - Diversity of amyloid beta protein fragment [1-40]-formed channels.
AB  - 1. The lipid bilayer technique was used to characterize the biophysical and
      pharmacological properties of several ion channels formed by incorporating
      amyloid beta protein fragment (AbetaP) 1-40 into lipid membranes. Based on the
      conductance, kinetics, selectivity, and pharmacological properties, the following
      AbetaP[1-40]-formed ion channels have been identified: (i) The AbetaP[1-40]
      formed "bursting" fast cation channel was characterized by (a) a single channel
      conductance of 63 pS (250/50 mM KCl cis/trans) at +140 mV. 17 pS (250/50 mM KCl
      cis/trans) at -160 mV, and the nonlinear current-voltage relationship drawn to a
      third-order polynomial, (b) selectivity sequence PK > PNa > PLi = 1.0:0.60:0.47,
      (c) Po of 0.22 at 0 mV and 0.55 at +120 mV, and (d) Zn2+-induced reduction in
      current amplitude, a typical property of a slow block mechanism. (ii) The
      AbetaP[1-40]-formed "spiky" fast cation channel was characterized by (a) a
      similar kinetics to the "bursting" fast channel with exception for the absence of
      the long intraburst closures, (b) single channel conductance of 63 pS (250/50
      KCl) at +140 mV 17 pS (250/50 KCl) at -160 mV, the current-voltage relationship
      nonlinear drawn to a third-order polynomial fit, and (c) selectivity sequence PRb
      > (iii) The AbetaP[1-40]-formed medium conductance channel was charcterized by
      (a) 275 pS (250/50 mM KCl cis/trans) at +140 mV and 19 pS (250/50 mM KCl
      cis/trans) at -160 mV and (b) inactivation at Vms more negative than -120 and
      more positive than +120 mV. (iv) The AbetaP[1-40]-formed inactivating large
      conductance channel was characterized by (a) fast and slow modes of opening to
      seven multilevel conductances ranging between 0-589 pS (in 250/50 mM KCI) at +140
      mV and 0-704 pS (in 250/50 mM KCl) at -160 mV. (b) The fast mode which had a
      conductance of <250 pS was voltage dependent. The inactivation was described by a
      bell-shaped curve with a peak lag time of 7.2 s at +36 mV. The slow mode which
      had a conductance of >250 pS was also voltage dependent. The inactivation was
      described by a bell-shaped curve with a peak lag time of 7.0 s at -76 mV, (c) the
      value of PK/Pcholine for the fast mode was 3.9 and selectivity sequence PK > PCs
      > PNa > PLi = 1.0:0.94:0.87:0.59. The value of PK/Pcholine for the slow mode was
      2.7 and selectivity sequence PK > FNa > PLi > PCs = 1.0:0.59:0.49:0.21, and (d)
      asymmetric blockade with 10 mM Zn2+-induced reduction in the large conductance
      state of the slow mode mediated via slow block mechanism. The fast mode of the
      large conductance channel was not affected by 10 mM Zn2+. 2. It has been
      suggested that, although the "bursting" fast channel, the "spiky" fast channel
      and the inactivating medium conductance channel are distinct, it is possible that
      they are intermediate configurations of yet another configuration underlying the
      inactivating large conductance channel. It is proposed that this heterogeneity is
      one of the most common features of these positively-charged cytotoxic amyloid
      formed channels reflecting these channels ability to modify multiple cellular
      functions. 3. Furthermore, the formation of beta-sheet based oligomers could be
      an important common step in the formation of cytotoxic amyloid channels.

PMID- 11569538
TI  - Butyrylcholinesterase-Mediated enhancement of the enzymatic activity of trypsin.
AB  - 1. Acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BuChE, EC
      3.1.1.8) are enzymes that catalyze the hydrolysis of esters of choline. 2. Both
      AChE and BuChE have been shown to copurify with peptidases. 3. BuChE has also
      been shown to copurify with other proteins such as transferrin, with which it
      forms a stable complex. In addition, BuChE is found in association with beta
      amyloid protein in Alzheimer brain tissues. 4. Since BuChE copurifies with
      peptidases, we hypothesized that BuChE interacts with these enzymes and that this
      association had an influence on their catalytic activities. One of the peptidases
      that copurifies with cholinesterases has specificity similar to trypsin, hence,
      this enzyme was used as a model to test this hypothesis. 5. Purified BuChE causes
      a concentration-dependent enhancement of the catalytic activity of trypsin while
      trypsin does not influence the catalytic activity of BuChE. 6. We suggest that,
      in addition to its esterase activity, BuChE may assume a regulatory role by
      interacting with other proteins.

PMID- 11569539
TI  - SPME/GC-MS characterization of volatiles associated with methamphetamine: toward
      the development of a pseudomethamphetamine training material.
AB  - The headspace profiles of eleven methamphetamine (MA) samples have been analyzed
      using solid-phase microextraction/gas chromatography-mass spectrometry (SPME/GC
      MS). Nine of the eleven are illicit MA seizures from the Southwest U.S. border.
      One sample is methamphetamine base synthesized in the Drug Enforcement
      Administration (DEA) Southwest Laboratory, and the remaining sample is
      pharmaceutical-grade methamphetamine hydrochloride that is used to make training
      aids for drug detecting canines. In addition. volatiles associated with 1-phenyl
      2-propanone (P2P), a methamphetamine precursor, have been identified for
      comparison with those found in methamphetamine seizure and the two reference
      samples. Eighty-seven different compounds were identified from all the samples,
      not including simple hydrocarbons and aldehydes. Only seven occur consistently in
      all seizure samples, and these are: acetic acid, benzaldehyde, acetophenone, P2P,
      1-phenyl-1,2-propanedione (P12P), 3-phenyl-3-buten-2-one, 1-chloro-1-phenyl-2
      propanone. Dimethyl sulfone, a common cutting agent in methamphetamine. was found
      in six of the nine seizure materials. When the reference methamphetamine and P2P
      samples are included, only two compounds are common to all twelve samples, and
      these are benzaldehyde and P2P. As such, these two compounds are likely
      candidates for use in a pseudomethamphetamine (PM) formulation, and their
      effectiveness in eliciting a canine response is being evaluated before actual
      deployment.

PMID- 11569540
TI  - Use of dynamically coated capillaries for the routine analysis of
      methamphetamine, amphetamine, MDA, MDMA, MDEA, and cocaine using capillary
      electrophoresis.
AB  - A rapid, accurate, precise, reproducible, economical, and environmentally gentle
      method using capillary electrophoresis (CE) is presented for the routine analysis
      of methamphetamine, amphetamine, MDA, MDMA, MDEA, and cocaine in seized drugs.
      The methodology uses a 32 cm by 50 microm capillary (length to detector 23.5 cm)
      with a commercially available buffer kit and diode array UV detection. Dynamic
      coating of the capillary surface is accomplished by flushing with base for 1 min,
      a proprietary polycation for 1 min, and then a proprietary polyanion for 2 min.
      This approach provides a relatively high and stable electroosmotic flow (EOF),
      even at low pHs. The background electrolyte (BGE) contains 75 mM phosphate buffer
      (pH 2.5) with the same polyanion as above. Using this methodology, amphetamine,
      methamphetamine, MDA, MDMA, MDEA, and an internal standard (n-butylamphetamine)
      are baseline resolved in less than 5 min. The run-to-run migration time %RSDs and
      peak area %RSDs are typically <0.3% and <2.1%, respectively. The day-to-day and
      capillary-to-capillary migration time %RSDs are <1.5% and <2.1%, respectively.
      The %RSDs of the relative migration times compared with the internal standard on
      a day-to-day and capillary-to-capillary basis are <0.2% and <0.06%, respectively.
      The linear dynamic range using peak areas range from 0.003 to 0.10 mg/mL. The
      correlation coefficients are >0.9998, with all calibration curves passing at or
      near the origin. Similar data are obtained for cocaine and its internal standard
      henyltoloxamine. None of the compounds usually encountered in illicit samples
      interfere with the target compound (e.g., methamphetamine and cocaine) or the
      internal standard. Quantitative results for synthetic mixtures and seized
      exhibits are in good agreement with actual values, and also with results obtained
      from other techniques. The relatively high EOF for the dynamically coated
      capillary system allows for the screening of basic, acidic, and neutral
      adulterants in drug seizures; identification is facilitated by the use of
      automated UV library searches.

PMID- 11569541
TI  - Forensic determination of ricin and the alkaloid marker ricinine from castor bean
      extracts.
AB  - Liquid chromatography/mass spectrometry (LC/ MS) and matrix assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) MS methods were developed for
      the presumptive identification of ricin toxin and the alkaloid marker ricinine
      from crude plant materials. Ricin is an extremely potent poison, which is of
      forensic interest due to its appearance in terrorism literature and its potential
      for use as a homicide agent. Difficulties arise in attempting to analyze ricin
      because it is a large heterogeneous protein with glycosylation. The general
      protein identification scheme developed uses LC/MS or MALDI-TOF for size
      classification followed by the use of the same instrumentation for the analysis
      of the tryptic digest. Fragments of the digest can be searched in an online
      database for tentative identification of the unknown protein and then followed by
      comparison to authentic reference materials. LC fractionation or molecular weight
      cutoff filtration was used for preparation of the intact toxin before analysis.
      Extracts from two types of castor beans were prepared using a terrorist handbook
      procedure and determined to contain 1% ricin. Additionally, a forensic sample
      suspected to contain ricin was analyzed using the presented identification scheme
      (data not shown). The identification of the alkaloid ricinine by GC/MS and LC/MS
      was shown to be a complementary technique for the determination of castor bean
      extracts.

PMID- 11569542
TI  - The analysis of forensic samples using laser micro-pyrolysis gas chromatography
      mass spectrometry.
AB  - Laser micropyrolysis gas chromatography-mass spectrometry is used for the
      analysis of paint, photocopier toner, and synthetic fiber materials to test the
      forensic potential of this emerging technology. It uses a laser microprobe to
      selectively target very small parts of the materials for GC-MS analysis. Whereas
      the paint and the toner samples were amenable to direct laser pyrolysis, the
      synthetic fibers proved transparent to the 1064 nm laser radiation. The
      difficulty with the fibers demonstrates that a specific laser wavelength may not
      be appropriate for all types of materials. Nevertheless, the fibers were able to
      be indirectly pyrolyzed by impregnation in a strongly absorbing graphite matrix.
      A vast array of hydrocarbon pyrolysates was detected from the different materials
      studied. Unique product distributions were detected from each sample and in
      sufficient detail to facilitate individual molecular characterization (i.e.,
      molecular fingerprinting). The integrity of the laser data were confirmed by
      comparison to data obtained from the same samples by the more conventional
      pyroprobe pyrolysis GC-MS method. The high spatial resolution and selectivity of
      the laser method may be advantageous for specific forensic applications, however,
      further work may be required to improve the reproducibility of the data.

PMID- 11569543
TI  - In situ identification and analysis of automotive paint pigments using line
      segment excitation Raman spectroscopy: I. Inorganic topcoat pigments.
AB  - Several applications of Raman spectroscopy in the forensic sciences have recently
      been demonstrated, but few have involved the analysis of paints. Undoubtedly,
      this is a reflection of the sample degradation problems often encountered when a
      visible or near-infrared laser is focused on a light-absorbing matrix. In this
      study, a dispersive CCD Raman spectrometer (785 nm) was used in a configuration
      which collected scattered light from an excitation region 3 mm long and 80 microm
      wide, instead of from a focused spot. Sample degradation was not observed, and
      Raman spectra of automotive paints of all colors were readily obtained. Most of
      the paints analyzed were U.S. automobile original finishes (1974 to 1989) from
      the Reference Collection of Automotive Paints, and the inorganic pigments
      examined were those which had been identified previously by infrared spectroscopy
      in finishes from this collection. Prominent peaks of rutile were observed in
      Raman spectra of light-colored nonmetallic finishes for both monocoats and
      basecoat/clearcoat systems, and the rutile peaks are readily distinguished from
      those of anatase. The lead chromates (Chrome Yellow, Molybdate Orange, and silica
      encapsulated versions of the two) are the strongest Raman scatterers among the
      pigments examined, and Chrome Yellow was identified by Raman spectroscopy in
      several yellow and orange nonmetallic monocoats for which infrared absorptions of
      this pigment were not observed. Raman spectroscopy also provides an unequivocal
      means to distinguish Chrome Yellow from Molybdate Orange. This is particularly
      helpful for the analysis of paints containing light pigment loads or encapsulated
      pigments since the two formulations cannot be differentiated by infrared
      spectroscopy in such cases. The iron-containing pigments, ferric oxide, hydrous
      ferric oxide, and Prussian Blue, are relatively weak Raman scatterers, but peaks
      of hydrous ferric oxide and Prussian Blue were observed in spectra of paints
      containing heavy pigment loads. Because no sample preparation is required. Raman
      spectroscopy provides an excellent means to rapidly screen reference panels for
      the presence of certain pigments, and some examples of the differences in Raman
      spectra which occur for paints having similar colors are presented.

PMID- 11569544
TI  - Determining explosivity part II: comparison of small-scale cartridge tests to
      actual pipe bombs.
AB  - The small-scale explosivity device (SSED) has been used to assess the explosive
      power of a number of low explosives-smokeless powders (WC-870, Red Dot, Bullseye,
      Winchester Action Pistol, and IMR-PB), Pyrodex, black powder, and an improvised
      explosive (TATP). The device requires 2 g of energetic material, a heavy-walled
      containment vessel, and a standard blast shield to permit use in most
      laboratories. The data from the SSED are compared with the fragmentation of pipe
      bombs which contained 300 to 700 g of powder. The SSED provided the same relative
      ordering of explosivity as suggested by the fragmentation of the real devices. In
      addition, the SSED was used to evaluate the chemical residue remaining after an
      explosion. Issues in using the device such as optimal detonators and restricted
      reaction volume were probed using three high explosives--TNT, Tetryl, and RDX.

PMID- 11569545
TI  - Sustained combustion of an animal carcass and its implications for the
      consumption of human bodies in fires.
AB  - When a human body is found with significant portions of its torso and limbs
      destroyed yet with comparatively minor damage to head, hands and feet, the
      mechanism of such destruction defies ready explanation, since exposure to
      external fires, particularly those involving flammable liquids, usually results
      in the destruction of hands, feet, limbs, and head prior to significant
      combustion of the large mass of the torso. Previous tests by these authors have
      demonstrated the conditions necessary to promote combustion of a body: the
      presence of adequate body fat, presence of a porous, rigid char to act as a wick,
      and an external flame source sustained for several minutes to char the body and
      cause the subcutaneous fat to begin rendering. In the test reported here, a
      freshly-slaughtered pig carcass with a net weight of 215 lb. (95 kg) was wrapped
      in a cotton blanket and placed on a carpet-covered plywood panel. The fire was
      initiated using 1 L of gasoline poured on the shoulder area of the blanket
      wrapped carcass. The gasoline burned off within 4 min, having ignited a large
      area of the blanket and adjoining carpet. Flames from those fuel packages
      resulted in the establishment of a steady-state fire sustained by the rendering
      of the body fat, with the necessary wick provided by the charred cotton blanket
      and carpet. The heat release rate of this fire was 60+/-10 kW, with flames less
      than 12 in. (0.35 m) high for its duration. The fire sustained itself by the
      rendering process for more than 6 1/2 h from ignition, at which time it was
      extinguished. An average mass loss rate of 1.5 g/s (5.3 kg/h) was observed during
      the self-sustained fire. Extensive destruction of the carcass (more than 60% by
      weight) included reduction of large bones to a fragile, ashen state. Other test
      data will demonstrate the similarity between subcutaneous fat from human and
      porcine sources. The implications for the reconstruction of accidental and
      homicidal fires involving such destruction will be discussed.

PMID- 11569546
TI  - Chemical development of latent fingerprints: 1,2-indanedione has come of age.
AB  - The performance of 1,2-indanedione as a latent fingerprint reagent on some types
      of paper was found to exceed that of DFO, the leading fluorogenic fingerprint
      reagent. It even exceeds the performance of the sequence, DFO, followed by
      ninhydrin. No new prints could be observed when ninhydrin was applied after
      indanedione. On a large number of actual exhibits (used checks) indanedione
      developed 46% more identifiable prints than the sequence DFO-ninhydrin. A
      standard procedure for fingerprint development by indanedione is proposed. Best
      results are obtained with a 0.2% indanedione solution in HFE7100 solvent
      containing 7% ethyl acetate, but no acetic acid. It can be recommended to start
      using 1,2-indanedione, which is already commercially available, in actual
      fingerprint casework.

PMID- 11569548
TI  - Systematic analysis of bulk blue ballpoint pen ink by FTIR spectrometry.
AB  - A classifying method on bulk blue ballpoint pen ink has been studied by Fourier
      transform infrared (FTIR) spectroscopy. By using this method, a total of 108 blue
      ink samples have been divided into two groups depending on their main component.
      Spectral characteristics of these inks such as frequency and absorbance are
      described by way of artificial intelligence of pattern recognition, and 35
      subgroups from the 108 inks are distinguished by their correlation coefficient
      (lambda). Under heat or exposure to ultraviolet light a mode of change in the age
      of the inks has been obtained. This approach has provided a reliable and
      nondestructive method for the characterization of bulk ballpoint writing ink, and
      more importantly, it might be a basis for dating of the blue ballpoint pen ink.

PMID- 11569547
TI  - Latent fingerprint detection using a scanning Kelvin microprobe.
AB  - Electrochemical interactions between latent human fingerprints and metal surfaces
      in ambient air are investigated using a scanning Kelvin microprobe. Inorganic
      salts present in sweat deposited at fingerprint ridges locally depassivate the
      metal surface producing a Volta potential decrease of greater than 200 mV. Volta
      potential patterns may persist for months and prints may be visualized by
      potential mapping, even when overcoated with a polymer layer. Because the Volta
      potential differences are produced by involatile salts they persist when the
      organic components of the fingerprint residue have been volatilized by heating to
      600 degrees C.

PMID- 11569549
TI  - DNA-based identification and molecular systematics of forensically important
      Sarcophagidae (Diptera).
AB  - Sarcophagid flies have many characteristics that make them ideal forensic
      indicators. However, their utility is severely limited because it is difficult or
      impossible to determine the species of a sarcophagid larva, and in many instances
      an adult specimen, based on anatomy. We developed a database of mitochondrial DNA
      sequence data that makes it possible to identify all sarcophagid species likely
      to be found feeding on a human corpse at an urban location in Canada or the USA.
      Analyses were based on a 783 base pair region of the gene for cytochrome oxidase
      subunit one (COI). The species analyzed, including some of no forensic importance
      that were included for purposes of phylogenetic comparisons, were members of the
      genera Sarcophaga, Peckia, Blaesoxipha, Rovinia, Wohlfahrtia, Brachicoma (all
      Sarcophagidae), and Musca (Muscidae).

PMID- 11569550
TI  - The fin de millenaire duty to warn or protect.
AB  - At the turn of the millennium, the authors summarize the evolution of a
      clinician's duty to protect third persons from a patient's violent acts over the
      past half century, with special emphasis on jurisprudential developments in the
      last decade. Four evolutionary periods are identified: Pre-Tarasoff, Inception,
      Diversification, and Retreat. The period of Retreat from Tarasoff in the nineties
      is characterized by the following approaches to Tarasoff: adoption, statutory
      containment, rejection of a duty to warn, rejection of a duty to control
      voluntary patients, and proactive circumscription of any protective duties. A
      more rational jurisprudential approach would permit some measure of flexibility
      for the proper exercise of clinical discretion.

PMID- 11569551
TI  - Investigating the role of screen violence in specific homicide cases.
AB  - Despite a substantial body of research indicating a significant and causal
      empirical relationship between viewing what the authors label "screen violence"
      and behaving violently, little attention has been paid to the forensic
      psychological and psychiatric investigation of these phenomena in specific
      homicide cases. Through the analysis of seven cases of homicide, mostly committed
      by adolescents, the authors introduce five concepts--aggression immersion, theme
      consistency, scene specificity, repetitive viewing, and self-editing--for
      advancing such investigations.

PMID- 11569552
TI  - The contract murderer: patterns, characteristics, and dynamics.
AB  - A case of an independent professional contract murderer, who killed over 100
      people, is reported. After eluding law enforcement for 30 years, the subject
      killed several associates who he believed could implicate him in various crimes.
      These homicides eventually led to his arrest, since the victims were individuals
      who could be linked to him. This hit man had a background of poverty and
      childhood abuse but, as an adult, had pursued a middle-class lifestyle and kept
      his family totally separate from his criminal career. In addition, he had a
      number of characteristics that helped him carry out his crimes in a highly
      planned, methodical, and organized manner: he had adept social judgment;
      personality traits of orderliness, control, and paranoid vigilance; useful
      defense mechanisms of rationalization and reframing; and an exceptional ability
      to encapsulate emotions. This case is discussed within the context of contract
      murder, a crime that occurs relatively frequently and is probably increasing; yet
      it often goes undetected, the arrest rate is low, and the offender is rarely
      studied.

PMID- 11569553
TI  - Focal neurological complications of handcuff application.
AB  - The application of handcuffs may result in compression neuropathies at the wrist.
      The frequency of these complications is unknown. Twelve of 190 (6.3%) consecutive
      subjects kept in police custody presented distal neurological symptoms possibly
      related to handcuff application. The duration of handcuffing was significantly
      longer in patients with neurological symptoms than in patients without
      neurological symptoms (mean +/- SD: 3.7+/-5.2 h vs. 1.8+/-2.6 h, P = 0.02). A
      long duration of handcuff application and, possibly, the existence of somnolence
      or acute alcohol intoxication could be predisposing factors to handcuff
      neuropathy. A prospective study of clinical and electrophysiological detection
      and follow up is needed.

PMID- 11569554
TI  - Abstracting data from medical examiner/coroner reports: concordance among
      abstractors and implications for data reporting.
AB  - The purpose of this study was two-pronged: 1) to determine the level of
      concordance (agreement) between multiple records abstractors who extracted
      defined data elements from printed medical examiner/coroner (ME/C) death
      investigation records; and 2) to identify data items for which improved reporting
      could facilitate the effective use of ME/C reports and data. Four hundred ninety
      four printed death investigation records were obtained from 224 medical
      examiner/coroner offices throughout the United States. Trained abstractors were
      asked to extract information for 110 data elements from investigative reports.
      Additional data elements for each toxicology workup were abstracted from
      toxicology laboratory reports and six-digit AIS codes were also abstracted for
      each injury as described in autopsy reports. The ability of multiple abstractors
      to identify each data element and identically abstract the data was assessed
      using Kappa statistical methods. Level of agreement for many data elements was
      very good (>0.9), but for some data elements agreement was marginal to poor,
      especially for items related to toxicology, the nature of specific injuries, and
      dates, times of the occurrence of death and injury. Many data items can be easily
      abstracted from ME/C records. However, some data items seem difficult to abstract
      reliably in all cases. Standardizing the report formats used by ME/Cs and/or
      standardizing the electronic storage of ME/C data would make the abstraction of
      such data easier and improve the usefulness of ME/C data.

PMID- 11569555
TI  - Fatal descent from height in New York City.
AB  - All deaths due to descent from height that underwent autopsy at the Manhattan
      Office of Chief Medical Examiner of New York City over a two year period (1997
      1999) were reviewed. The scene and autopsy findings, psychiatric history, and
      toxicology results were examined. There were 120 deaths: 77 suicides, 36
      accidents, 5 undetermined, and 2 homicides. Psychiatric illness was reported in
      86% of suicides. The toxicological detection of psychiatric medications supports
      the high percentage of psychiatric disease in the suicide group. In the
      accidental group, the detection of ethanol and illicit drugs was higher (36%)
      than expected from the case investigation and similar to the suicide group (29%).
      Accidental falls by women made up fewer than 3% of all manners. Due to the
      variation in the extent of injuries, it is unwise to attempt to conclude how high
      a person descended based on the autopsy findings. Descents into water commonly
      have minimal findings on external examination with marked internal injuries. The
      methods of investigation and criteria for death certification using the study
      results are discussed.

PMID- 11569556
TI  - Postmortem blood free and total morphine concentrations in medical examiner
      cases.
AB  - This purpose of this study was to determine the relationships between postmortem
      free morphine and total morphine levels in a large series of medical examiner
      morphine and heroin related deaths. Free morphine, total morphine, and 6
      monoacetylmorphine (6-MAM) concentrations were measured by gas chromatography
      mass spectrometry (GC-MS) in 87 medical examiner cases over 20 months. The mean
      total morphine concentration, mean free morphine concentration, and mean percent
      free morphine for all cases were: 2.3 mg/L (SD 5.2 mg/L), 0.5 mg/L (SD 1.6 mg/L),
      and 19.4% (SD 22.8%); respectively. Regression analyses showed weak correlations
      between total and free morphine concentrations over the entire concentration
      range (0 to 36.6 m/L, r = 0.603, n = 91) and over a subset concentration range of
      0 to 1.0 mg/L (r = 0.369, n = 54). Twenty-three out of 56 (41%) tested positive
      for 6-MAM, indicative heroin abuse cases. Lower total and free morphine
      concentrations and a higher percent free morphine were found in individuals with
      detectable 6-MAM. Comparing blood concentrations for cases with and without
      detectable 6-MAM demonstrated mean total morphine concentrations of 0.9 mg/L
      versus 2.1 mg/L (p = 0.05), mean free morphine concentrations of 0.3 mg/L versus
      0.4 mg/L (p = 0.21), and mean percent free morphine of 34.7% versus 13.7% (p <
      0.003), respectively. Our findings demonstrate higher free to total morphine
      ratios in individuals with detectable 6-MAM than in individuals without 6-MAM.
      The database established in this study may assist medical examiners in the
      evaluation of postmortem blood opiates regarding the cause of death in opiate
      related ingestion cases.

PMID- 11569557
TI  - Deposition of 7-aminoflunitrazepam and flunitrazepam in hair after a single dose
      of Rohypnol.
AB  - In recent years, there has been a notable increase in the number of reports on
      drug-facilitated sexual assault. Benzodiazepines are the most common so-called
      "date-rape" drugs, with flunitrazepam (Rohypnol) being one of the most frequently
      mentioned. The aim of this study was to determine whether flunitrazepam and its
      major metabolite 7-aminoflunitrazepam could be detected in hair collected from
      ten healthy volunteers after receiving a single 2 mg dose of Rohypnol using solid
      phase extraction and NCI-GC-MS. Such data would be of great importance to law
      enforcement agencies trying to determine the best time interval for hair
      collection from a victim of drug-facilitated sexual assault in order to reveal
      drug use. Ten healthy volunteers (eight women and two men, 21 to 49 years old)
      participated in the study. The following hair samples were collected from each
      volunteer: one before flunitrazepam administration, and 1, 3, 5, 14, 21, and 28
      days after. In five volunteers, 7-aminoflunitrazepam was detected 24 h after
      flunitrazepam administration and remained in hair throughout the entire 28-day
      study period (0.6-8.0 pg/mg). In two cases, 7-aminoflunitrazepam appeared in hair
      21 days after drug intake (0.5-2.7 pg/mg), and in two subjects 14 days later (0.5
      5.4 pg/mg). In one volunteer, 7-aminoflunitrazepam was detected on day 14 and 21
      but concentrations were below the quantitation limit. Flunitrazepam was detected
      in some samples but all concentrations were below the quantitation limit (0.5-2.3
      pg/mg).

PMID- 11569558
TI  - Adherence of forensic odontologists to the ABFO bite mark guidelines for suspect
      evidence collection.
AB  - Boards and associations within forensic science have long been accepted as
      vehicles for the development and dissemination of protocols and recommendations
      for practice. Recent controversies surrounding bite mark analyses have brought
      the methods and practices of forensic dentists to the attention of both the
      courts and the media. In the mid-eighties the American Board of Forensic
      Odontology developed guidelines for bite mark analysis in response to unfavorable
      commentaries on the discipline by legal observers. The purpose of this study is
      to examine the adherence of board certified and noncertified forensic dentists to
      the guidelines for collection of evidence from bite mark suspects. A
      questionnaire was employed during an American Academy of Forensic Sciences
      meeting. Results showed that, in general, when the odontologists collected
      evidence they did adhere to the guidelines, although collection of salivary
      samples was not common. Of concern is the large number of odontologists who do
      not collect their own evidence from suspects. Police officers or other
      individuals often perform this task and therefore the guidelines must be
      disseminated to these groups to ensure that the maximum yield is obtained from
      bite mark evidence. A review of the materials used to collect evidence is also
      included with details of applications in forensic science.

PMID- 11569559
TI  - Metric variation in the human occipital bone: forensic anthropological
      applications.
AB  - Sex and race variation of the occipital bone have been previously investigated,
      but particular examination of the effect of age and ancestry on sexual dimorphism
      has not been addressed. This paper examines morphological variation associated
      with sex and ancestry in the condylar region of the occipital bone and the effect
      of age and ancestry on the estimation of sex. Models previously published by
      Holland are also tested, and methodological problems are addressed. The results
      indicate that age does not have an effect on sexual dimorphism, but that whites
      exhibit greater, although not significantly, more sexual dimorphism than blacks.
      Significant sex and ancestry variation is present in the condylar region of the
      occipital bone, but neither sex nor ancestry could be estimated accurately using
      measurements of this anatomical region defined by Holland.

PMID- 11569560
TI  - Detection of gamma-butyrolactone (GBL) as a natural component in wine.
AB  - The compound gamma-butyrolactone (GBL) was found in extracts from samples of
      unadulterated wines. This finding indicates that GBL is a naturally occurring
      component in some wines and may be present in similar products. The concentration
      detected was approximately 5 microg/mL and was easily observed using a simple
      extraction technique followed by GC/MS analysis. These results illustrate the
      need to carefully examine an allegedly adulterated sample's matrix before
      determining a sample was laced with GBL.

PMID- 11569561
TI  - The use of capillary electrophoresis in the detection of monomethylamine and
      benzoate ions in the forensic examination of explosives residues.
AB  - Capillary electrophoresis (CE) is used in the ATF Forensic Science Laboratories
      for the analysis of inorganic ions commonly encountered in post-blast residues
      including monomethylamine (MMA) and benzoate ions. Monomethylamine nitrate is
      found in Tovex, a water gel explosive. Sodium benzoate is added to Pyrodex, as a
      fuel and burn rate modifier. In the analysis of explosive residues, these ions
      are used as an indicator for the presence of Tovex and Pyrodex. Traditionally,
      these two ions, along with other ions of interest were analyzed by spot tests and
      ion chromatograph (IC). CE is currently being used in place of spot tests as a
      confirmation technique for IC.

PMID- 11569562
TI  - Extraction of human DNA for PCR from chewed residues of betel quid using a novel
      "PVP/CTAB" method.
AB  - Residues of chewed betel quid (BQ) are often found on crime scenes in Taiwan and
      possibly some of the Southeast Asian countries. Although these residues are
      important biological evidences relating to the suspects, the forensic analysis of
      BQ evidence has been hindered by failures in extraction of human DNA for PCR
      analysis. Therefore, it is a prerequisite for relevant forensic casework to
      establish a reliable method for extracting DNA from chewed BQ residues. Three
      conventional methods (salt/chloroform, 5% Chelex-100 resin, and QIAamp) were
      first tested for extraction of human DNA from 33 mock BQ samples, which had been
      stored for less than two months, and 50 four-year-old forensic BQ samples. PCR
      amplifications from the HLA-DQA1&PM and the STR loci were then used to test the
      quality of the extracted DNA. For the mock samples, three observations were made.
      First, PCR amplification of DNA extracted by using these conventional methods had
      low success rate. Second, the addition of extra Taq DNA polymerase could
      compensate the lost enzyme activities due to putative inhibitors and, thus,
      increase the yield. Third, using the Centricon-100 column to remove putative
      inhibitors substantially improved the efficiency of PCR. However, for the four
      year-old forensic BQ samples, none of the attempts for PCR were successful. In
      order to solve the problem in PCR analysis of DNA from old BQ samples, we
      developed a DNA extraction method based on the use of polyvinyl pyrrolidone (PVP)
      and cetyltrimethylammonium bromide (CTAB), which bind to two common classes of
      PCR inhibitors in plants, polyphenols, and polysaccharides, respectively. The
      result showed that this "PVP/CTAB" method is completely successful for the mock
      BQ samples, and 92% (46 out of 50) successful for the four-year-old forensic BQ
      samples. To our best knowledge, this is the first report of a reliable method for
      the extraction of human DNA for PCR from chewed BQ residues. This method should
      provide a useful means for forensic identification in countries where betel
      chewing is common.

PMID- 11569563
TI  - AmpFlSTR Profiler Plus and AmpFlSTR COfiler analysis of tissues stored in
      GenoFix, a new tissue preservation solution for mass disaster DNA identification.
AB  - A preliminary study was conducted to assess the capability of a new alcohol-based
      tissue fixative, GenoFix, to preserve DNA from biopsy tissues stored at room
      temperature and/or -20 degrees C in a freezer, for subsequent short tandem repeat
      (STR) DNA typing analysis. Fresh human smooth muscle samples were stored at room
      temperature in GenoFix for one month and up to one year and seven months before
      being processed using the megaplex STR systems, AmpFlSTR Profiler Plus and
      AmpFlSTR COfiler. Alternatively, muscle tissues in GenoFix were placed at -20
      degrees C in a freezer for up to 3 1/2 years following two to three months in the
      fixative at room temperature. DNA analysis was also carried out on tissues stored
      in GenoFix for one month at room temperature and subsequently paraffin-embedded
      and stored at room temperature for four years. The AmpFlSTR Profiler Plus and
      AmpFlSTR COfiler STR profiles produced, using DNA extracted from all fixed tissue
      samples, were of very good quality. The fluorescent signals were well balanced
      across the nine STR loci or six loci comprised in the megaplexes surveyed and
      profiles showed no differences with those observed for the control blood of the
      respective donor patients. Continuous exposure to GenoFix at room temperature (up
      to one year and seven months) did not compromise the STR typing analysis of the
      fixed tissues. No adverse effects were noted on the STR typeability of tissues
      fixed with GenoFix and stored at -20 degrees C in a freezer for up to 3 1/2
      years. STR profiles generated from the paraffin-embedded tissues fixed in GenoFix
      were of excellent quality. This preliminary study suggests that GenoFix can be
      used to store tissue samples at room temperature for up to one year and seven
      months or at -20 degrees C in a freezer for longer storage (up to 3 1/2 years).
      This new and odorless tissue fixative promotes tissue and DNA preservation in a
      very effective manner and as such may prove useful in criminal investigations or
      mass disaster identifications carried out in remote locations and in which a
      small or large number of tissue samples are collected for further analyses.

PMID- 11569564
TI  - TWGDAM validation of the AmpFlSTR Profiler Plus and AmpFlSTR COfiler STR
      multiplex systems using capillary electrophoresis.
AB  - Prior to forensic implementation, a profiling system requires validation
      following the recommendations presented by the Technical Working Group on DNA
      Analysis Methods (TWGDAM). In this work two such systems, AmpFlSTR Profiler Plus
      and AmpFfSTR COfiler have been validated according to the guidelines provided by
      TWGDAM. Profiler Plus and COfiler simultaneously amplify nine and six STR loci
      respectively; both also amplify a portion of the amelogenin gene. Performance of
      the two STR multiplex systems under conditions set forth by TWGDAM was robust and
      reproducible, indicating that these systems are suitable for use in forensic
      analysis. Additionally, specific sections of the TWGDAM validation guidelines are
      especially valuable in terms of familiarizing users with particular limitations
      of the systems prior to taking on casework.

PMID- 11569565
TI  - NIST mixed stain studies #1 and #2: interlaboratory comparison of DNA
      quantification practice and short tandem repeat multiplex performance with
      multiple-source samples.
AB  - The Mixed Stain Study 1 (MSS1, Apr.-Nov. 1997) and Mixed Stain Study 2 (MSS2,
      Jan.-May 1999) evaluated multiplexed short-tandem repeat (STR) DNA typing systems
      with samples containing DNA from more than one source. These interlaboratory
      challenge studies evaluated forensic STR measurement, interpretation, and
      reporting practice using well-characterized samples of very different analytical
      difficulty. None of the relatively few errors reported in either exercise
      resulted in a false identification of a reference source; several errors in
      evaluating the unknown source in three-source samples would hinder matching the
      profile in any archival database. None of the measurement anomalies reported is
      associated with any particular STR multiplex; all DNA amplification anomalies are
      associated with inefficient DNA extraction, inaccurate DNA quantitation, and/or
      analytical threshold policies.

PMID- 11569566
TI  - Communicated threats and violence toward public and private targets: discerning
      differences among those who stalk and attack.
AB  - A computation of false positive and false negative rates concerning the
      probability that directly communicated written or oral threats predict subsequent
      violent behavior yields a striking difference between "public" and "private"
      targets. Among private targets, communicated threats appear to increase risk, but
      are so common that they have little predictive value. On the other hand, public
      targets are unlikely to receive a direct threat from those who approach to
      attack. The author suggests that the most parsimonious explanation for this
      difference is the type, or mode of violence, that is apparent. Private targets
      appear to be most likely victimized by affective violence, wherein the
      emotionally reactive subject will immediately shove, push, punch, slap, choke,
      fondle, or hair pull the victim without the use of a weapon, usually in response
      to a perceived rejection or humiliation. Public targets are most likely to be
      victimized by predatory violence, which is planned, purposeful, cognitively
      motivated, opportunistic rather than impulsive, and often involves a firearm.
      Implications for risk assessment are discussed.

PMID- 11569568
TI  - Detection of cocaine and its metabolites in breast milk.
AB  - A method was developed for measuring cocaine and its metabolites,
      benzoylecgonine, ecgonine methyl ester, norcocaine, ecgonine ethyl ester,
      cocaethylene, and m-hydroxybenzoylecgonine, in breast milk by gas
      chromatography/mass spectrometry. Limits of detection for this method ranged from
      2.5 to 10 ng/mL, and limits of quantitation ranged from 5 to 50 ng/mL. For each
      of the compounds measured by this method, linear response was demonstrated to 750
      ng/mL. Breast milk was collected from 11 mothers who admitted to drug use during
      pregnancy and ten drug-free volunteers serving as control subjects. Cocaine was
      detected in six of the specimens obtained from drug-exposed subjects, and in none
      of the drug-free control subjects. In breast milk specimens where cocaine and one
      or more of its metabolites were detected, the concentration of parent compound
      was greater than any of the metabolites. The highest cocaine concentration found
      was over 12 microg/mL. Breast-fed infants of cocaine abusing mothers may be
      exposed to significant amounts of drug orally.

PMID- 11569567
TI  - Blind trials of an onsite saliva drug test for marijuana and opiates.
AB  - The objective of these clinical trials was to calculate the performance, limit of
      detection, specificity and sensitivity of a novel, semi-quantitative immunoassay
      for drugs of abuse in saliva and to determine operator bias when measured blind
      by four different operators. The test is based on lateral flow gold particle
      technology coupled with digital photography to provide a semi-quantitative end
      point. The performance of the test was compared with that of enzyme immunoassays
      and GC/MS methods. Volunteers consumed marijuana or codeine and their saliva was
      collected 0.25 to 24 h later with the Cozart RapiScan collection device. The
      sensitivity and specificity of the opiate test were both 100%+/-10.4% for codeine
      for 9 h after dosing. The cutoff of the marijuana test at 10 ng/mL THCA was too
      high to detect marijuana use for more than a few hours after smoking. There was
      no operator bias because the results were presented in written form either as
      "positive" or "negative" for each of the five drug classes on the screen of the
      hand-held reader.

PMID- 11569569
TI  - Pelvic age estimation using actual specimens and remote images.
AB  - Age estimates of the auricular surface (sacro-iliac joint) of the ilium taken
      from bony specimens, 35 mm slides, and digital images were compared for 29 intact
      specimens from archaeological contexts. Results demonstrate that age estimates
      from all photographic and digital images may result in significantly differing
      estimates of age than those from bony specimens. Of the imaging techniques, 35 mm
      slides provided estimates most similar to those from bony specimens. Digital
      images provided age estimates that varied more from bony specimens. In general,
      photographic and digital images may offer researchers a way of documenting age
      information that would otherwise be unavailable or delayed. Yet, caution should
      be used when age estimates are derived solely from images rather than from bony
      specimens.

PMID- 11569570
TI  - The use of the D-, L- aspartic ratio in decalcified collagen from human dentin as
      an estimator of human age.
AB  - Among the methods dealing with the age estimation, the evaluation of the ratio of
      the D-, L- form of the aspartic acid in tissues with a low metabolic turnover is
      considered to be the most precise. We introduced demineralization of the dentin
      with 0.5 M EDTA adjusted to pH = 7.4. The advantage of such a procedure is that
      after demineralization we obtained pure insoluble protein (collagen) and soluble
      noncollagenous proteins in one step. In this study we analyzed insoluble
      collagen. The amino acids obtained after the hydrolysis were derivatized into TFA
      isopropyl esters and analyzed by gas chromatography on Chirasil L-Val capillary
      column. We analyzed human dentin from the lower canines. The correlation
      coefficient was 0.93 for our set of 71 persons. The result concurred with those
      of other scientists.

PMID- 11569571
TI  - DNA profiling of trace evidence--mitigating evidence in a dog biting case.
AB  - A young girl was the victim of a severe dog attack. An animal, suspected of
      having caused the attack, was later impounded for investigation. Microclots of
      blood, recovered from the dog's fur, were analyzed by STR DNA. Results showed
      that this blood was not related to the biting. Other forensic evidence--hairs,
      fibers, and odontology--failed to connect a particular animal to the attack. The
      implications of these findings for the dog and its owners are discussed as well
      as other forensic methods for resolving such cases.

PMID- 11569572
TI  - DNA testing of Klinefelter's syndrome in a criminal case using XY chromosomal STR
      multiplex-PCR.
AB  - We report genetic typing of Klinefelter's syndrome applied to casework in
      forensic DNA testing. In this case, by using extracted DNA from body samples
      (muscle and bones), we could identify two distinct X alleles in two out of three
      X-STR loci (HPRTB and ARA), in addition to Y alleles (DYS390, DYS393). The extra
      X was found to have originated from father, and the victim turned out to have
      47XXY Klinefelter's syndrome. The victim was a 30-year-old male, born from
      relatively elderly parents as a second child. His father was a severe alcoholic
      and had been malnourished for more than 20 years at the moment of his birth. He
      exhibited slight mental retardation as a child, and belonged to a criminal group
      as an adult. The method presented here was useful to accurately diagnose sex
      chromosomal abnormality instead of conventional chromosomal analysis and Xg blood
      group typing. A subtype of this syndrome, 48 XXXY or mosaic, for example, could
      be identified if the intensity of the overlapped X bands were calculated.

PMID- 11569573
TI  - Asphyxia due to angiotensin converting enzyme (ACE) inhibitor mediated angioedema
      of the tongue during the treatment of hypertensive heart disease.
AB  - This report describes seven deaths caused by angioedema of the tongue related to
      angiotensin converting enzyme (ACE) inhibitors. These seven cases were received
      in our office between 1998 and 2000. In that time frame we performed
      approximately 2000 autopsies. The cases involved African-American men and women,
      aged 51 to 65 years, all of whom had been prescribed an ACE inhibitor for the
      treatment of hypertensive heart disease. In each case, the external examination
      revealed markedly swollen tongues. The autopsies confirmed massive tongue
      swelling due to angioedema, and some patients also had swelling of the lips,
      pharynx, and larynx. Toxicologic analyses on postmortem blood samples were
      negative for ethanol and drugs of abuse. Although oral and pharyngeal swelling
      related to angioedema is well known in the clinical literature, its fatal
      potential has rarely been described.

PMID- 11569574
TI  - Glycine toxicity and unexpected intra-operative death.
AB  - A rare complication of the use of glycine irrigation fluid during prostatic
      surgery in a 69-year-old man is described. Following cystolithopexy and
      transurethral resection of the prostate for benign prostatomegaly, abdominal
      distension developed with increasing ventilatory pressures. Despite
      retroperitoneal fluid evacuation at subsequent urgent laparotomy, cardiac arrest
      occurred that was not amenable to resuscitation. At autopsy a traumatic defect in
      the posterior bladder wall filled with calculus debris was confirmed that did not
      communicate with the peritoneal cavity. Hyponatremia with markedly elevated
      levels of blood, urine, and body fluid glycine were demonstrated. Death was,
      therefore, attributed to glycine toxicity following tracking of glycine through a
      surgical defect in the posterior bladder wall. Careful dissection of surgical
      sites is required in such cases to demonstrate any additional trauma that may be
      associated with the fatal episode. Analysis of body fluids for glycine and
      electrolytes is also necessary to assist in the determination of possible
      mechanisms of death.

PMID- 11569575
TI  - Fatal overdose of zopiclone in an elderly woman with bronchogenic carcinoma.
AB  - The death of a 72-year-old woman with respiratory debilitation due to
      bronchogenic carcinoma is described. She overdosed herself with probably 200 to
      350 mg of zopiclone. Zopiclone, quantitated by HPLC in femoral postmortem blood,
      was found to be 1.9 mg/L (4.8 micromol/L). This level is higher than many other
      zopiclone fatalities reported. We report a case where only zopiclone was
      detected.

PMID- 11569576
TI  - Y-chromosomal short tandem repeat haplotypes at the loci DYS393, DYS19, DYS392,
      and DYS385-I/II, DYS390, DYS389-I/II, and DYS391 in a Filipino population sample.

PMID- 11569577
TI  - Allele frequencies of pentanucleotide STR D6S957 in Chinese and German
      populations.

PMID- 11569578
TI  - Allele frequencies for three STR loci D1S1612, D2S1391, and D17S2196 in Chinese
      population.

PMID- 11569579
TI  - Distribution of HLA-DQA1 and amplitype PM locus alleles in a Turkish population
      sample.

PMID- 11569580
TI  - Distribution of HumTPOX, HumvWA, HumTH01 alleles in a Turkish population sample.

PMID- 11569581
TI  - Commentary on: Barros de Castro IA, Rinzler CM, Rumjanek FD. Allele frequency
      distributions for twelve STR loci in a Brazilian population. J Forensic Sci
      2000;45(4):941.

PMID- 11569582
TI  - Commentary on: Ely SF, Hirsch CS. Asphyxial deaths and petechiae. J Forensic Sci
      2000;45(6):1274-1277.

PMID- 11569583
TI  - Judgments of social appropriateness by children and adolescents with autism.
AB  - Children and adolescents with autism (autism group, n = 19) and those without
      autism (Nonautism group, n = 19) of similar age and IQ were asked to make
      judgments of the social appropriateness of 24 videotaped, staged scenes with
      adult actors. Each scene depicted an appropriate or an inappropriate interaction.
      Half contained verbalizations, and half did not. After each scene, the
      participant was asked: (1) Was that o.k. or was something wrong with it? If the
      participant judged the scene was wrong, she or he was asked: (2) What was wrong
      with it?; and (3) Why was that wrong? Both groups correctly identified
      inappropriate behaviors most of the time, and correct behaviors almost all of the
      time. However, the Nonautism group detected inappropriate behaviors significantly
      more often than the Autism group, for verbal but not nonverbal scenes. It was
      also significantly easier for both groups to identify inappropriate behaviors in
      the nonverbal than in the verbal scenes. Ratings of the explanations given for
      Question 3 differed significantly between the groups for verbal but not for
      nonverbal scenes, with Nonautism participants more likely to give explanations
      involving social norms and principles, and the Autism group more likely to give
      explanations that were irrelevant or idiosyncratic.

PMID- 11569584
TI  - Enhancing social problem solving in children with autism and normal children
      through computer-assisted instruction.
AB  - Children with autism have difficulty in solving social problems and in generating
      multiple solutions to problems. They are, however, relatively skilled in
      responding to visual cues such as pictures and animations. Eight distinct social
      problems were presented on a computer, along with a choice of possible solutions,
      and an option to produce alternative solutions. Eight preschool children with
      autism and eight matched normal children went through 10 training sessions
      interleaved with 6 probe sessions. Children were asked to provide solutions to
      animated problem scenes in all the sessions. Unlike the probe sessions, in the
      training sessions problem solutions were first explained thoroughly by the
      trainer. Subsequently these explanations were illustrated using dynamic
      animations of the solutions. Although children with autism produced significantly
      fewer alternative solutions compared to their normal peers, a steady increase
      across probe sessions was observed for the autistic group. The frequency of new
      ideas was directly predicted by the diagnostic category of autism. Results
      suggest young children with autism and their normal peers can be taught problem
      solving strategies with the aid of computer interfaces. More research is required
      to establish whether such computer-assisted instruction will generalize to
      nontrained problem situations in real-life contexts.

PMID- 11569585
TI  - Replacing prelinguistic behaviors with functional communication.
AB  - This study evaluated the effectiveness of a teacher-implemented intervention
      package designed to replace prelinguistic behaviors with functional
      communication. Four young children with autism participated in a multiple-probe
      design across three communicative functions. Initially, three existing
      communication functions were selected for each child. Next, the existing
      prelinguistic behaviors that the children used to achieve these functions were
      identified. Replacement forms that were considered more recognizable and symbolic
      were defined to achieve these same functions. After a baseline phase, teachers
      received inservice training, consultation, and feedback on how to encourage,
      acknowledge, and respond to the replacement forms. During intervention, the
      replacement forms increased and prelinguistic behaviors decreased in most cases.
      The results suggested that the teacher-implemented intervention was effective in
      replacing prelinguistic behaviors with alternative forms of functional
      communication.

PMID- 11569586
TI  - Siblings relationships of children with autism.
AB  - This study investigated sibling relationships of children with autism compared to
      children with Down syndrome and siblings of normally developing children. Ninety
      siblings (30 per group) between the ages of 8 and 18 participated in this study.
      Results indicated that sibling relationships in families of children with autism
      were characterized by less intimacy, prosocial behavior, and nurturance than
      those of the two comparison groups. Both siblings of children with autism and
      siblings of children with Down syndrome reported greater admiration of their
      sibling and less quarreling and competition in their relationships relative to
      normally developing comparison children.

PMID- 11569587
TI  - A review of subtyping in autism and proposed dimensional classification model.
AB  - Autism has been divided into subtypes based on social interaction/communication,
      developmental level, or both. The validity of subtyping systems and the extent to
      which they overlap were examined. According to this review, a single subtyping
      system capable of accounting for the symptom heterogeneity in autism has not yet
      been proposed; however, evidence supports the presence of a three-factor
      continuum containing at least four subgroups. Foremost among directions for
      future research is the need for comprehensive studies in which medical screening,
      careful selection of measures, and longitudinal data collection are included.

PMID- 11569588
TI  - Exploration of psychometric properties of the developmental behavior checklist.
AB  - The Developmental Behavior Checklist (DBC; Einfeld & Tonge, 1995) is one of a
      very small number of psychopathology assessment instruments designed specifically
      for use with children and adolescents with mental retardation. In the present
      study, a factor analysis of the DBC was performed using a sample of 531 children
      and adolescents. This analysis revealed a factor structure sharing a good deal of
      overlap with the factor analyses of the DBC's developers. Furthermore, the high
      levels of internal consistency of the DBC subscales were replicated. Further
      research and development is needed on the DBC and other instruments for children
      and adolescents with mental retardation.

PMID- 11569589
TI  - Attentional processes in autism.
AB  - Attentional processes in individuals with high-functioning autism were compared
      with a matched control group. Participants for the study were 103 children and
      adults with autism and 103 control subjects. Measures administered corresponded
      to Mirsky et al.'s (1991) factor analysis of tests of attention. Diminished
      performance was noted on measures that loaded on the Focus-Execute and Shift
      factors, but not on the Sustain and Encode factors. For tests in which
      psychomotor speed was used as the score, and the difference between groups was
      significant, covariance analyses were performed, using tests of basic motor
      functions as covariates. This procedure led to attenuation to the point of
      nonsignificant differences in the case of some of the attention tests. Thus, this
      comprehensive analysis of attention in individuals with high-functioning autism
      only found differences on measures in which the task placed demands on cognitive
      flexibility or psychomotor speed. Thus, purported attention deficits in autism
      may actually be primary deficits in complex decision making or psychomotor
      abilities.

PMID- 11569590
TI  - Ask the editor. Asperger syndrome.

PMID- 11569591
TI  - The impact of men's and women's retirement on marital relations: a comparative
      analysis.
AB  - The study examined whether men's and women's retirement have a differential
      impact on several aspects of marital life: Power relations (as reflected in
      decision-making), spousal resources, division of household tasks, and quality of
      marriage. Questionnaires were distributed to a sample of 519 pre-retired and
      retired Israelis. The findings indicate that in general, both men's and women's
      retirement have a similar impact on marital relations in all of the areas
      examined. No appreciable change in spousal resources was found after retirement,
      but there was evidence of change in decision-making patterns about spending time
      and carrying out feminine and general tasks. Retired respondents of both sexes
      reported fewer marital complaints than the pre-retired respondents, but also
      expressed less marital enjoyment. It was also found that men's retirement has a
      different impact than women's retirement on decisions about house-hold affairs
      and performance of feminine tasks. In addition, gender-based differences were
      found in several areas, irrespective of employment status. The women reported
      higher quality of marriage than did the men, and more resources for strengthening
      the family, whereas the men perceived themselves as making more decisions in the
      important areas of life, as more hardy, and as controlling the family's financial
      resources.

PMID- 11569592
TI  - Adding aging and gender to the women's health agenda.
AB  - The complex interaction of medical, social, and economic factors that affect
      women's wellness as they age requires a new paradigm that bridges the gap between
      those who are concerned about aging issues and those concerned about women's
      health. In this article, we begin this endeavor by advancing three interrelated
      themes: (1) there is a gendered relationship between socioeconomic structures and
      health over time; (2) there are gender-specific implications of health care
      financing and policy; and (3) there are health consequences to the gendered
      nature of caregiving.

PMID- 11569593
TI  - Responding to social service and health care needs of aging women veterans.
AB  - This is a study about aging women veterans who served in the military during the
      1940s, 1950s and 1960s. The Veterans Administration (VA) represents a formal
      network of health and support services that offers a wide range of benefits for
      veterans. However, older women veterans may not be aware of, or benefit from, all
      that may be available to them. The purpose of this study was to learn about aging
      women veterans' knowledge and utilization of services and benefits available
      through the VA. Telephone interviews were conducted in April 1998 with 220 women
      veterans in Massachusetts who were age 60 + years. There was generally strong
      identification with veterans' organizations among the women surveyed. These women
      veterans were likely to receive medical care-a major benefit available through
      the VA. The benefits veterans were least likely to know about included services
      that may be particularly relevant and helpful to an aging veteran, such as long
      term care and home adaptation services. Strategies are suggested to enhance
      outreach efforts to aging veterans.

PMID- 11569594
TI  - Experiencing undesired daily life events, instrumental functioning, social
      support and well-being of Israeli elderly women: comparison between
      caregivers/non-caregivers for adult children with mental retardation.
AB  - The purpose of the study was to examine the extent to which 160 mothers who care
      for an adult child with mental retardation differ in respect to undesired daily
      life events, instrumental functioning, social support and well-being from a
      comparably matched group of age peers. Findings indicated that caregivers for
      adult children with mental retardation reported more undesired daily life events
      in comparison to the matched group. However, no differences were found in respect
      to their instrumental functioning, social support and well-being. A detailed
      analysis showed significant variations in measures of undesired daily life events
      and social support.

PMID- 11569596
TI  - "Dumbing down" in dental education.

PMID- 11569595
TI  - Risk status related to knowledge of osteoporosis in older women.
AB  - BACKGROUND: The objectives of this study were to: (1) identify common risk
      factors for osteoporosis, (2) relate risk factors to knowledge of osteoporosis,
      and (3) teach prevention, diagnosis, and treatment strategies for women at risk.
      METHODS: A descriptive exploratory design was used to assess the osteoporosis
      risk factors of 211 women age 60 and over living in the community in a large city
      in a southwestern state. Participants in 15 different sites completed a
      demographic data form, an osteoporosis Risk Factor Card, and a pre-test about
      osteoporosis. After participating in a 30-minute educational program, they
      completed a post-test. RESULTS: The mean score on the Risk Factor Card was 3.00
      out of a total possible score of 11. The most frequent risk factors identified
      were race, small frame, and early menopause. Using a two-tailed Pearson
      correlation, there was no significant correlation between being at risk and a
      person's knowledge of osteoporosis prior to or after the educational program.
      Using a one-tailed t-test, there was a significant increase in knowledge from pre
      test to post-test. CONCLUSION: Additional educational programs might increase
      awareness of risk factors and behaviors likely to enhance bone health. All older
      women should be encouraged to initiate discussion regarding osteoporosis with
      their health care providers. Physicians, nurses, social workers, and others also
      should assess their client's knowledge of osteoporosis.

PMID- 11569597
TI  - The face of a child: children's oral health and dental education.
AB  - Dental care is the most common unmet health care need of children. Those at
      increased risk for problems with oral health and access to care are from poor or
      minority families, lack health insurance, or have special health care needs.
      These factors place more than 52 percent of children at risk for untreated oral
      disease. Measures of access and parental report indicate unmet oral health needs,
      but do not provide guidance as to the nature of children's oral health needs.
      Children's oral health needs can be predicted from their developmental changes
      and position in the life span. their dependency and environmental context, and
      current demographic changes. Specific gaps in education include training of
      general dentists to care for infants and young children and those with special
      health care needs, as well as training of pediatric providers and other
      professionals caring for children in oral health promotion and disease
      prevention. Educational focus on the technical aspects of dentistry leaves little
      time for important interdisciplinary health and/or social issues. It will not be
      possible to address these training gaps without further integration of dentistry
      with medicine and other health professions. Children's oral health care is the
      shared moral responsibility of dental and other professionals working with
      children, parents, and society. Academic dental centers hold in trust the
      training of oral health professionals for society and have a special
      responsibility to train future professionals to meet children's needs. Leadership
      in this area is urgently needed.

PMID- 11569598
TI  - Factors considered by new faculty in their decision to choose careers in academic
      dentistry.
AB  - To determine the characteristics of new dental faculty and what factors
      influenced them to choose academic careers, a survey was sent to deans at all
      U.S. dental schools to be distributed to faculty with length of service of four
      years or less. Responses were received from 240 individuals. About half of the
      respondents had been in private practice for an average of eight years, and 20
      percent had military experience averaging almost sixteen years. A majority had
      postgraduate training and 60 percent had specialty training. Nearly 32 percent of
      new faculty were female and 80 percent were U.S. citizens. Analyses of responses
      to survey items indicated that correlated factors in the survey fell into the
      following empirical categories: teaching and scholarship, income and
      indebtedness, research, work schedule, influence of mentors and role models, and
      long-term aspirations. In general, the respondents identified factors relating to
      teaching and scholarship to be the most important influences on their choice of
      academic careers, while concerns about income and indebtedness were the most
      important negative considerations in this regard. Other positive factors
      identified by the survey related to the influence of mentors and role models,
      long-term aspirations, and research. Age, private practice experience, and
      military experience were found to particularly influence the new faculty members'
      responses to items concerning income and indebtedness, and citizenship influenced
      responses to factors relating to research. The data from this select group of
      dentists support the current view that inequities in income of dental faculty
      compared to private practitioners and student debt are important concerns in
      choosing academic careers. Importantly, the desire to teach and participate in
      scholarly activities are important attractions in academic careers. Mentoring
      activities and creation of opportunities for career development are crucial
      factors in developing interest in academics among graduate dentists.

PMID- 11569599
TI  - Factors influencing pursuit and satisfaction of academic dentistry careers:
      perceptions of new dental educators.
AB  - New dental educators (n = 280) with zero to five years full-time teaching
      experience were surveyed to ascertain their perceptions regarding salary, work
      environment, and workload to determine the impact of these factors on faculty
      recruitment and retention. Work environment was the most frequently reported
      factor for considering and maintaining an academic dentistry position.
      Educational resources, facilities, salary, and benefits were ranked as moderately
      important for considering an academic position. Mentoring, startup funds for
      research, and external private practice opportunities were also reported as
      moderately important for maintaining a position. Other factors of concern to new
      faculty included quality of administration and leadership, reputation of program,
      professional development opportunities, faculty autonomy, and reasonable criteria
      for tenure and promotion. These findings suggest that resources, strategies, and
      formal mentoring programs that provide direction and guidance in the areas of
      teaching, promotion, and tenure for new educators should be considered for
      implementation in our dental schools.

PMID- 11569600
TI  - Access to dental care: a historical review of medicaid eligibility growth and
      dental productivity decline.
AB  - The present dilemma in providing dental services to the indigent and Medicaid
      recipients throughout this nation has generated considerable controversy as to
      the evolution of the problem. Most states recognize that there are deficiencies
      in the provision of dental services to these populations and are seeking
      resolutions. While state licensing board practices and dental professional
      society politics have been the object of criticism as contributing to if not
      causing of this problem, other rational and statistically valid explanations for
      the current difficulty exist. As an explanation for access to care issues, this
      paper explores the decline in the national numbers of dental practitioners and
      concomitant dental productivity. Furthermore, it relates those parameters to the
      dramatic rise in the utilization and demand for dental services resulting from a
      robust economy, population growth trends, and changes in state and federal
      Medicaid legislation that increase numbers of Medicaid-eligible recipients. While
      these general trends are national in scope and application, the state of North
      Carolina and its experience will be used to fully explore the impact of these
      trends at the state and local level.

PMID- 11569601
TI  - Use of fissure sealant retention as an outcome measure in a dental school
      setting.
AB  - The purpose of this study was to describe and assess the use of fissure sealant
      retention as a quality measure of the delivery system for pediatric dentistry.
      The Pediatric Dentistry Section at the Ohio State University College of Dentistry
      adopted Sealant retention as a measure of quality. Sealant retention in first and
      second molars was evaluated at each six-month recall appointment. Sealants were
      categorized as satisfactory or unsatisfactory. Two hundred five sealants were
      evaluated between March 1998 and March 1999. The mean age of the patients at the
      time of sealant evaluation was 14.0 +/- 2.9. Mean sealant retention period was
      29.8 +/- 23.2 months, with a range of 0.9 to 148 months. Median sealant retention
      period was 23.2 months. Overall, 75.6 percent of the sealed teeth were classified
      as satisfactory. Use of this data in making improvements is discussed. Our
      results indicate that the use of sealant retention is a suitable measure for
      quality of care in pediatric dentistry.

PMID- 11569602
TI  - Small business needs assessment: a comparison of dental educators' responses with
      SBDC survey results.
AB  - A primary focus of dental education is to teach students the knowledge, skills,
      and values essential for practicing dentistry. However, the preparation of
      dentists to manage a business is frequently cited as inadequate. A survey was
      prepared to assess teachers' opinions of business instructional topics:
      challenges; desired training; employee benefits; learning resources; importance
      of business topics; and appropriateness of time allocations. The purpose of this
      project is to compare opinions of teachers of dental practice management with key
      management aspects reported for service businesses by the Small Business
      Development Center (SBDC). Practice management teachers from forty-eight (89
      percent) schools responded to the survey. They indicated that several challenges
      confronting dentists are similar to other service businesses. Dentists, however,
      rank customer relations appreciably higher. In order of importance of teaching
      topics, the practice management teachers rank ethics and personnel management as
      a high priority and planning as a low priority. Awareness of the similarities and
      differences in the perceptions of practice management teachers and businesspeople
      may result in instructional improvements.

PMID- 11569603
TI  - Relationships of admissions data and measurements of psychological constructs
      with psychomotor performance of dental technology students.
AB  - Abstract: The psychomotor skills required in dental laboratory technology and
      dentistry are similar. Dental educators have recognized the problems in selecting
      from among dental school applicants those with potential psychomotor skills. The
      purpose of this study was to examine the relationships of admissions data and
      measurements of psychological constructs of dental technology students with their
      psychomotor performance in first-semester dental laboratory courses. The
      dependent variables selected for the study were grades from three laboratory
      courses. Significant positive correlations (p<.05) were noted between all
      laboratory grades and previous college hours, previous college GPA, interview
      scores, field dependence-independence scores, block counting, trust,
      straightforwardness, and dutifulness. These data indicate that individual
      differentiation in learning ability, visual or spatial perception, and
      personality do affect psychomotor learning and should be taken into consideration
      in the design and execution of teaching and training curricula.

PMID- 11569604
TI  - Validation of an instrument to measure dental students' use of, knowledge about,
      and attitudes towards computers.
AB  - Currently, no validated survey instrument exists to measure dental students' use
      of, knowledge about, and attitudes towards computers. Several studies have
      surveyed students about their knowledge and opinions regarding computers, but
      none of them has established the reliability and validity of the instrument(s)
      used. A measurement study to validate a preliminary survey for dental students
      was conducted. The preliminary instrument contained five scales: computer use,
      information resource use, computer knowledge, capabilities of computer systems,
      and effects of computers on dental practice. Selected variables were summarized
      descriptively, and a factor analysis for each scale was performed. In addition,
      construct validity was assessed through correlational analyses among several
      variables. Three hundred seventy surveys distributed to students at nine dental
      schools generated 156 responses (42 percent response rate). Sixty-four percent of
      respondents were male, 36 percent female. Respondents used computers an average
      approximately four hours per week, and most had begun using computers in 1991.
      All survey scales except computer use were unidimensional. Computer use required
      a two-factor solution that distinguished between clinical and nonclinical uses of
      computers. The instrument can be used for a demonstration study, but should be
      continuously refined and validated.

PMID- 11569605
TI  - Community partnering and coalition development: finding solutions to oral health
      care problems together.

PMID- 11569606
TI  - Dental enamel formation and its impact on clinical dentistry.
AB  - The nature of tooth enamel is of inherent interest to dental professionals. The
      current-day clinical practice of dentistry involves the prevention of enamel
      demineralization, the promotion of enamel remineralization, the restoration of
      cavitated enamel where demineralization has become irreversible, the vital
      bleaching of dental enamel that has become discolored, and the diagnosis and
      treatment of developmental enamel malformations, which can be caused by
      environmental or genetic factors. On a daily basis, dental health providers make
      diagnostic and treatment decisions that are influenced by their understanding of
      tooth formation. A systemic condition during tooth development, such as high
      fever, can produce a pattern of enamel defects in the dentition. Knowing the
      timing of tooth development permits estimates about the timing of the
      disturbance. The process of enamel maturation continues following tooth eruption,
      so that erupted teeth can become less susceptible to decay over time. Mutations
      in the genes encoding enamel proteins lead to amelogenesis imperfecta, a
      collection of inherited diseases having enamel malformations as the predominant
      phenotype. Defects in the amelogenin gene cause X-linked amelogenesis imperfecta,
      and genes encoding other enamel proteins are candidates for autosomal forms. Here
      we review our current understanding of dental enamel formation, and relate this
      information to clinical circumstances where this understanding may be
      particularly relevant.

PMID- 11569607
TI  - Transferring genes to salivary glands.
AB  - This review provides a brief description of gene transfer studies using salivary
      glands as the target tissue. The aggregate results demonstrate the potential
      clinical value of this methodological approach for managing several conditions
      lacking fully satisfactory conventional treatments. Routine clinical applications
      are still seven to ten years away, primarily because of the need for improved
      gene transfer vectors. Overall, this body of work provides the dental educator
      with a substantive example of how biotechnological progress will significantly
      affect the treatment of oral problems in the near future.

PMID- 11569608
TI  - ADEA annual survey of clinic fees and revenue: 1998-1999 academic year.
AB  - The American Dental Education Association's 1998-1999 Survey of Clinic Fees and
      Revenue obtained data by which to report, by school, clinic revenue information
      per undergraduate student. Fifty of the fifty-five U.S. dental schools responded
      to the survey. The median revenue per third-year student was $6,313. It was
      $11,680 for fourth-year students. Clinic revenue data was also obtained by type
      of postdoctoral program. The postdoctoral general dentistry programs had the
      highest per student clinic revenues, at over $59,000 per AEGD student and almost
      $35,000 per student of GPR programs. Other areas of the survey provided
      information regarding clinic fees by type of program, levels of uncompensated
      care by type of program, clinic revenue by source of payment, and dental school
      fees as a percent of usual and customary private practice fees.

PMID- 11569609
TI  - Identifying endothelium-derived hyperpolarizing factor: recent approaches to
      assay the role of epoxyeicosatrienoic acids.
AB  - Investigation of endothelial regulation of vascular reactivity and tone has led
      to the discovery of chemical mediators such as nitric oxide (NO) and prostacyclin
      (PGI2). Evidence has emerged indicating another as yet unidentified
      hyperpolarizing agent (endothelium-derived hyperpolarizing factor or EDHF) that
      is different from NO and PGI2 and exerts it effects through calcium-activated
      potassium channels (KCa). Previous studies to identify EDHF have been carried out
      using inhibitors that block NOS and COX before application of KCa channel and/or
      muscarinic receptor antagonists. Such pharmacological manipulation has
      complicated interpretation of results, clearly pointing to the need for altered
      approaches to verify previous studies. Evidence has emerged that potential EDHF
      candidates vary with vessel size, species and tissue beds, indicating that there
      may be more than one EDHF. To date, the most commonly described and best
      characterized of them all are a set of arachidonic acid metabolites,
      epoxyeicosatrienoic acids (EETs). These compounds are synthesized both intra- and
      extravascularly. Until recently, methodology to detect EETs in the
      microvasculature has been tedious and expensive, limiting the experimentation
      that is necessary to confirm EETs as an EDHF. This review describes state-of-the
      art methods for assaying EETs in biological samples, after summarizing evidence
      for EETs as an EDHF and introducing emerging concepts of the role of
      extravascular EETs in linking neuronal activity to localized blood flow during
      functional hyperemia.

PMID- 11569610
TI  - Strategy for modulation of central dopamine transmission based on the partial
      agonist concept in schizophrenia therapy.
AB  - The dopamine system is known to be closely involved in brain neuronal dysfunction
      and in diseases such as Parkinson's disease, Tourette's syndrome, attention
      deficit hyperactive disorder, generation of pituitary tumors and schizophrenia.
      According to the classical dopamine hypothesis on the pathology of schizophrenia,
      conventional antipsychotics has D2 dopamine receptor antagonistic profiles.
      However, the use of typical antipsychotics has several limitations; that is, some
      patients do not respond to them, they can even worsen negative symptoms, and they
      can provoke unacceptable extrapyramidal and endocrine side effects. To produce
      effective antipsychotics with reduced side effects, partial agonists to D2
      dopamine receptors (D2 receptors) have been developed. Despite the effectiveness
      of partial agonists for pre- and postsynaptic D2 receptors, administration of
      such drugs results in inconsistent clinical effects to ameliorate the symptoms of
      schizophrenia. Thus, strategies for obtaining ideal effective antipsychotics with
      reduced side effects are considered in this short review with respect to the
      intrinsic efficacies and affinities of the partial agonists, based on the partial
      agonist concept.

PMID- 11569611
TI  - Possible involvement of calcium-calmodulin pathways in the positive chronotropic
      response to angiotensin II on the canine cardiac sympathetic ganglia.
AB  - We investigated the ganglionic effects of angiotensin II (Ang II) and the signal
      transduction involved in the cardiac sympathetic ganglia by the direct
      administration of agents to the ganglia through the right subclavian artery and
      monitoring the heart rate as an indicator of the ganglionic function in pithed
      dogs. Ang II given i.a. caused increases in the heart rate, which was inhibited
      by the treatment with the AT1-receptor antagonist forasartan, but not by the AT2
      receptor antagonist PD-123319. The stimulation by Ang II, but not by
      acetylcholine, was inhibited after treatment with an inhibitor of phospholipase
      C, U-73122; a cell-permeant modulator of the Ins(1,4,5)P3 receptors, 2
      aminoethoxydiphenyl borate; an intracellular calcium and calcium-associated
      protein kinase inhibitor, HA-1077; calmodulin (CaM) inhibitor, W-7; Ca2+/CaM
      dependent protein kinase II inhibitor, KN-93; a selective protein kinase C
      inhibitor, calphostin C; and Na+H+ exchange inhibitor, dimethylamiloride. These
      results suggest that Ang II stimulates the ganglionic transmission at
      postsynaptic sites via the activation of AT1 receptor coupled to either
      activation of phospholipase C, phosphoinositide hydrolysis and subsequent
      increase in intracellular Ca2+ and activation of protein kinase C and Ca2+/CaM
      kinase II, although this ganglionic stimulation seems to involve, at least in
      part, the protein kinases-dependent increase of amiloride-sensitive Na+ inflow.

PMID- 11569612
TI  - Mechanism of a nitric oxide donor NOR 1-induced relaxation in longitudinal muscle
      of rat proximal colon.
AB  - We previously suggested that nitric oxide (NO)-mediated relaxation of the rat
      proximal colon is not associated with change in cyclic GMP content. We further
      studied the intracellular mechanism of NO-induced relaxation by measuring changes
      in tension and intracellular Ca2+ concentration ([Ca2+]i), simultaneously. NOR 1,
      NO donor, relaxed the longitudinal muscle of the rat proximal colon, which was
      precontracted by carbachol, with a concomitant decrease in [Ca2+]. ODQ, an
      inhibitor of soluble guanylate cyclase, partially inhibited the relaxant effect
      of only higher concentrations of NOR 1, but Rp-8-Br-cGMPS, an inhibitor of cyclic
      GMP-dependent protein kinase (PKG), did not have any effects on the relaxant
      effect of NOR 1. When the preparations were transferred to normal solution after
      the treatment with thapsigargin, an inhibitor of sarcoplasmic reticulum (SR) Ca2+
      ATPase, in the absence of Ca2+, contraction with a concomitant increase in
      [Ca2+]i occurred. NOR 1 did not show significant effects on the tension and
      [Ca2+]i in thapsigargin-treated preparations. In high K+-precontracted
      preparations, NOR 1 relaxed the preparations with a slight change in [Ca2+]i. The
      relaxant effect was significantly inhibited by ODQ and Rp-8-Br-cGMPS. These
      results suggest that NO induces the relaxation preferentially by acting
      thapsigargin-sensitive function of SR and in turn decreasing [Ca2+]i, although a
      cyclic GMP-PKG pathway is suggested under the experimental conditions of a high
      K+ concentration.

PMID- 11569613
TI  - Changes of tissue factor-dependent coagulant activity mediated by adhesion
      between polymorphonuclear leukocytes and endothelial cells.
AB  - The purpose of this study was to examine whether polymorphonuclear leukocytes
      (PMNs) facilitate a tissue factor, a physiologic initiator of coagulation in
      endothelial cells, -dependent coagulant activity (TF activity). The TF activity
      in bovine endothelial cells (BAECs) was significantly increased in a
      concentration-dependent manner by PMNs (1 x 10(5) - 1 x 10(7) cells/ml) without
      affecting the treatment of N-formyl-methionyl-leucyl-phenylalanine, a selective
      activator of PMNs, and the addition of PMNs finally resulted in cell damage as
      evaluated by the lactate dehydrogenase leakage method. In the same conditions, an
      increase of adhesion between PMNs and BAECs was also observed in a time-dependent
      manner. However, since direct adhesion of PMNs to BAECs was impossible by using
      the transwell, PMNs failed to induce any changes in the TF activity. Hence, the
      change of TF activity found here might be closely related to the PMNs adhesion to
      BAECs. Indeed, anti-intercellular adhesion molecule-1 (anti-ICAM-1) antibody
      blocked the increase of TF activity in BAECs. These findings suggest that PMNs
      could increase TF activity in endothelial cells, which is triggered by adhesion
      to endothelial cells through ICAM-1.

PMID- 11569614
TI  - Transactivation of core binding factor alpha1 as a basic mechanism to trigger
      parathyroid hormone-induced osteogenesis.
AB  - During 28-day culture of bone marrow- and calvaria-derived osteoblasts, the
      constant presence of parathyroid hormone (PTH)(1-34) retarded differentiation and
      nodule formation (NF) in a dose-dependent fashion (C-phase). In contrast,
      addition of PTH(1-34) in late stage cultures (from day 10 to 21) accelerated NF
      (A-phase). The stable production of such an A-phase allowed us to study the
      mechanism of bone anabolic action of PTH(1-34). Subcellular localization studies
      of core binding factor alpha1 (Cbfa1) and reporter assays provided the results
      indicating that in the A-phase, PTH(1-34) triggers its bone anabolic action via
      enhancement of Cbfa1 transactivation. RT-PCR and Northern blot analyses revealed
      that alkaline phosphatase, osteocalcin and bone sialoprotein expression decreased
      in the C-phase and increased in the A-phase; however, expression of other bone
      proteins (Cbfa1, PTH/PTH-related peptide-receptor, osteopontin, collagen I
      alpha1, collagen I alpha2, vitamin K-dependent gamma-glutamyl carboxylase) did
      not change in a phase transition-related manner. Ovariectomized osteopenic mice,
      treated with PTH(1-34) (4 and 40 microg/kg, s.c., every other day, 4 or 6 weeks),
      recovered lost bone, displayed elevated nuclear localization of Cbfal in tibiae
      without alteration of its cytosolic level and exhibited upregulation of
      expressions of the same set of proteins (alkaline phosphatase, osteocalcin and
      bone sialoprotein) in femora. These results obtained by a concerted study in
      vitro and in vivo suggest that PTH triggers its osteogenic action via promotion
      of the transactivation of Cbfa1.

PMID- 11569615
TI  - Effect of 1DMe, a neuropeptide FF analog, on acetylcholine release from myenteric
      plexus of guinea pig ileum.
AB  - Since neuropeptide FF (NPFF) is a putative neurotransmitter to exert anti-opioid
      activity, we examined the effects of [D-Tyr', (NMe)Phe3]neuropeptide FF (IDMe), a
      stable NPFF analog, on acetylcholine (ACh) release from a longitudinal muscle
      myenteric plexus (LMMP) preparation of guinea pig ileum in which opioids were
      known to inhibit ACh release when muscarinic autoinhibition was not fully
      activated. In the presence of atropine, 1DMe increased spontaneous and electrical
      field stimulation (EFS)-evoked ACh release in a concentration-dependent manner.
      Naloxone also increased ACh release. The stimulatory effects of 1DMe and naloxone
      were not additive. In the absence of atropine, 1DMe did not affect ACh release.
      Morphine decreased spontaneous and EFS-evoked ACh release in the presence of 1
      microM atropine. 1DMe as well as naloxone counteracted the inhibitory effects of
      morphine on EFS-evoked ACh release. The combination of 1DMe and naloxone was not
      more inhibitory than either drug alone. 1DMe had no appreciable effect on
      norepinephrine-induced inhibition of spontaneous and EFS-evoked ACh release.
      These results first demonstrated the effects of a NPFF analog on neurotransmitter
      release: 1DMe had a stimulatory effect on spontaneous and EFS-induced ACh release
      from the LMMP preparation of guinea pig ileum, probably by counteracting the
      inhibitory effect of endogenous opioids on ACh release.

PMID- 11569616
TI  - Involvement of beta2-adrenergic and mu-opioid receptors in antinociception
      produced by intracerebroventricular administration of alpha,beta-methylene-ATP.
AB  - The present study examined what kind of receptors are involved in the
      antinociception produced by intracerebroventricular (i.c.v.) administration of
      a,beta-methylene-ATP using antagonists at adrenergic, serotonin or opioid
      receptors. Antinociceptive effect of alpha,beta-methylene-ATP (10 nmol/rat) was
      significantly attenuated by subcutaneous pretreatment with propranolol and
      naloxone, but not phentolamine or methysergide, at a dose of 10 mg/kg. I.c.v.
      pretreatment with propranolol (100 nmol/rat), butoxamine (100 nmol/rat), ICI-I
      18,551 (100 nmol/rat) and naloxone (30 nmol/rat) significantly attenuated the
      antinociceptive effect of alpha,beta-methylene-ATP. However, i.c.v. pretreatment
      with atenolol (100 nmol/rat), naltrindole (30 nmol/rat) or nor-binaltorphimine
      (30 nmol/rat) did not show any significant effects. These results suggest that
      supraspinal beta2-adrenergic and mu-opioid receptors are involved in the
      antinociceptive effect of i.c.v. administered alpha,beta-methylene-ATP.

PMID- 11569617
TI  - Excitation of rat striatal large neurons by dopamine and/or glutamate released
      from nerve terminals via presynaptic nicotinic receptor (A4beta2 type)
      stimulation.
AB  - Previous in vivo experiments using rats anesthetized with chloral hydrate have
      revealed that nicotine applied iontophoretically increased firing of striatal
      neurons receiving excitatory dopaminergic input from the substantia nigra, and
      nicotine-induced firing was inhibited by domperidone, a dopamine D2 antagonist.
      The results suggest that nicotine increases release of dopamine from the
      terminals of dopaminergic neurons. Therefore, we performed the present patch
      clamp study using slice and acutely dissociated preparations of the rat striatum
      to elucidate the mechanisms underlying the nicotine-induced excitation of
      striatal neurons. Application of nicotine (100 microM) to large striatal neurons
      in slice preparations did not produce any effect on the resting membrane
      potential, but did increase the frequency of miniature postsynaptic potentials
      (mpps) and action potentials in all 15 neurons tested. The nicotine-induced
      increase in mpps and action potentials were inhibited during simultaneous
      application of domperidone; L-glutamic acid diethyl ester hydrochloride, a non
      selective glutamate receptor antagonist; and/or dihydro-beta-erythroidine, a
      central nicotinic acetylcholine receptor (alpha4beta2 type) antagonist.
      Postsynaptic current was not induced by nicotine applied by U-tube in 96% of
      acutely dissociated striatal neurons. The present findings suggest that nicotine
      mainly acts on the presynaptic nicotinic receptors in the nerve terminals to
      release neurotransmitters such as dopamine and/or glutamate, thereby activating
      the striatal large neurons.

PMID- 11569618
TI  - Effects of dehydroepiandrosterone on oleic acid formation in the liver of rats,
      mice and guinea pigs.
AB  - The purpose of the present study is to answer the question of whether there is a
      species difference in the effects of a pharmacological dose of
      dehydroepiandrosterone (DHEA) on the enzymes that participate in oleic acid
      (18:1) formation in the liver. Feeding a diet containing 0.5% (w/w) DHEA for 14
      days markedly increased the activities of acyl-coenzyme A (CoA) synthetase,
      palmitoyl-CoA chain elongase and stearoyl-CoA desaturase in the liver of rats and
      mice. These enzyme activities, however, were not changed by DHEA in guinea pigs.
      The treatments of rats and mice with DHEA markedly increased proportions of 18:1
      in hepatic lipids, especially phosphatidylcholine (selectively at C-2 position),
      triacylglycerol and cholesterol ester. DHEA caused no significant changes in acyl
      compositions of hepatic lipids of guinea pigs. The levels of DHEA or
      dehydroepiandrosterone sulfate (DHEAS) were markedly increased in serum and
      livers by DHEA administration to rats, mice and guinea pigs. High correlations
      were observed between hepatic levels of DHEA or DHEAS and stearoyl-CoA desaturase
      activities in rats. These results indicate that there are species differences in
      the inducing effects of DHEA or DHEAS on hepatic formation of 18:1 and that
      guinea pigs lack the machinery to induce the enzymes.

PMID- 11569619
TI  - Age-Related decrease in calcitonin gene-related peptide mRNA in the dorsal root
      ganglia of spontaneously hypertensive rats.
AB  - Age-related changes in levels of calcitonin gene-related peptide (CGRP) mRNA of
      the dorsal root ganglia was studied in 8-, 12- and 15-week-old spontaneously
      hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY).
      CGRP mRNA levels in SHR but not in WKY decreased with age. The contents of CGRP
      like immunoreactivities in the atrium and mesenteric artery of 15-week-old SHR
      were greater than those in age-matched WKY. These results suggest that the
      outflow of CGRP-containing nerves from the spinal cord and CGRP release from CGRP
      nerve terminals decreases in SHR.

PMID- 11569620
TI  - Effects of histidine on working memory deficits induced by the 5-HT1A-receptor
      agonist 8-OH-DPAT.
AB  - We investigated the effects of histidine on spatial memory deficits induced by
      the 5-HT1A-receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT).
      Working memory deficits were elicited by 8-OH-DPAT without affecting reference
      memory. Histidine improved the working memory deficit induced by 8-OH-DPAT at
      doses causing a significant increase in brain histamine content. This finding
      suggests that the histaminergic system regulates 8-OH-DPAT-induced working memory
      deficit.

PMID- 11569622
TI  - [Pneumonology in the year 2000].

PMID- 11569621
TI  - Mercury and autistic gut disease.

PMID- 11569623
TI  - 11th International Congress of Immunology. 22-27 July 2001. Stockholm, Sweden.
      Abstracts.

PMID- 11569624
TI  - EuroSpine 2001. Abstracts of the 3rd annual meeting of the Spine Society of
      Europe. September 2-8, 2001. Gothenburg, Sweden.

PMID- 11569626
TI  - Abstracts of the 50th annual meeting of the American Society of Tropical Medicine
      and Hygiene. Atlanta, Georgia, USA. November 11-15, 2001.

PMID- 11569625
TI  - The American Society of Human Genetics 51st annual meeting. October 12-16, 2001.
      San Diego, California, USA. Abstracts.

PMID- 11569629
TI  - [Abstracts of the 45th annual meeting of the Japanese Society for Medical
      Mycology. Tokyo, Japan, September 26-27, 2001].

PMID- 11569627
TI  - [Obstructive sleep apnea syndrome: a cardiovascular risk factor?].
AB  - INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is frequently associated
      with cardiovascular disease. We investigated endothelium-dependent and
      endothelium-independent nitric oxide-mediated vasodilatory function in
      normotensive patients with OSAS using the hand vein compliance technique.
      PATIENTS AND METHODS: Dose-response curves to the endothelium-dependent
      vasodilator bradykinin were obtained in 23 male subjects with OSAS and 12 male
      control subjects of comparable age, height, and weight. RESULTS: Mean (+/- SD)
      maximum dilation (Emax) to bradykinin was significantly lower in OSAS patients
      than in controls (59.8 +/- 26.0 vs. 94.8 +/- 9.5%, p < 0.0001). Mean vasodilation
      with nitroglycerin was not diminished in the OSAS group (90.7 +/- 30.5 vs. 100.3
      +/- 12.9% in controls; n.s.). In 11 OSAS patients, a follow-up investigation was
      performed after at least 2 months of treatment with nasal continuous positive
      airway pressure (CPAP): Emax to bradykinin rose from 54.5 +/- 19.2% to 111.5 +/-
      25.1% after treatment (p < 0.001). Mean vasodilation to nitroglycerin was
      unchanged. CONCLUSIONS: These results suggest that endothelium-dependent nitric
      oxide-mediated vasodilation is impaired in patients with OSAS due to an impaired
      function in the endothelial cells. This impairment is reversible with CPAP
      treatment.

PMID- 11569630
TI  - Abstracts of the joint 18th biennial meeting of the International Society for
      Neurochemistry and 32nd annual meeting of the American Society for
      Neurochemistry. Buenos Aires, Argentina, August 26-31, 2001.

PMID- 11569631
TI  - Abstracts of the 66th annual scientific meeting of the American College of
      Gastroenterology. October 22-24, 2001. Las Vegas, Nevada, USA.

PMID- 11569632
TI  - Ecological half-time of radiocesium from Chernobyl debris and from nuclear
      weapons fallout as measured in a group of subjects from the south of Sweden.
AB  - From 1960 to 1980 and between 1987 and 1994 the whole-body content of 17Cs, and
      when possible also 134Cs, was measured in a group of subjects living in the city
      of Lund, Sweden (55.7 degrees N, 13.2 degrees E). The results have been analyzed
      to estimate the effective ecological half-time of fallout radiocesium in humans
      living in the area. The Lund area (The Province of Skane) was subjected to a
      deposition of about 2 kBq m(-2) of pre-Chernobyl 137Cs from nuclear weapons
      testing and 1 kBq m(-2) of 137Cs from Chernobyl fallout in May 1986. The
      radiocesium from the nuclear weapons tests in the 1950's and 1960's still gave a
      significant contribution to the total 137Cs levels in humans in the post
      Chernobyl study period (1987-1994) of about 0.4 Bq per kg body weight, which was
      about 10% of the peak post-Chernobyl concentration level of 137Cs (3.5-4 Bq kg(
      1)) in 1987. The effective ecological half-time for 137Cs from Chernobyl was
      found to be 1.8 +/- 0.2 y. The aggregate transfer factor from deposition to mean
      activity concentration in man was estimated to be 3.6 Bq kg(-1)/kBq m(-2). These
      values may be compared with an effective ecological half-time of 1.3 y found in
      the reference group in the 1960's, and an aggregate transfer factor of 10 Bq kg(
      1)/kBq m(-2). This difference is largely explained by the continuous nature of
      the global fallout leading to contamination on growing crops whereas the
      Chernobyl fallout occurred just prior to the South Swedish growing season,
      leading to less efficient transfer to crops and to human diet. The average
      committed individual effective dose (50 y) from ingested 137Cs from the Chernobyl
      fallout was estimated to be 0.02 mSv and from the nuclear weapons fallout (1945
      1995) to be 0.20 mSv.

PMID- 11569633
TI  - Influences of parameter uncertainties within the ICRP 66 respiratory tract model:
      particle deposition.
AB  - Risk assessment associated with the inhalation of radioactive aerosols requires
      as an initial step the determination of particle deposition within the various
      anatomic regions of the respiratory tract. The model outlined in ICRP Publication
      66 represents to date one of the most complete overall descriptions of not only
      particle deposition, but of particle clearance and local radiation dosimetry of
      lung tissues. In this study, a systematic review of the deposition component
      within the ICRP 66 respiratory tract model was conducted in which probability
      density functions were assigned to all input parameters. These distributions were
      subsequently incorporated within a computer code LUDUC (LUng Dose Uncertainty
      Code) in which Latin hypercube sampling techniques are used to generate multiple
      (e.g., 1,000) sets of input vectors (i.e., trials) for all of the model
      parameters needed to assess particle deposition within the extrathoracic
      (anterior and posterior), bronchial, bronchiolar, and alveolar-interstitial
      regions of the ICRP 66 respiratory tract model. Particle deposition values for
      the various trial simulations were shown to be well described by lognormal
      probability distributions. Geometric mean deposition fractions from LUDUC were
      found to be within approximately +/- 10% of the single-value estimates from the
      LUDEP computer code for each anatomic region and for particle diameters ranging
      from 0.001 to 50 microm. In all regions of the respiratory tract, LUDUC
      simulations for an adult male at light exertion show that uncertainties in
      particle deposition fractions are distributed only over a range of about a factor
      of approximately 2-4 for particle sizes between 0.005 to 0.2 microm. Below 0.005
      microm, uncertainties increase only for deposition within the alveolar region. At
      particle sizes exceeding 1 microm, uncertainties in the deposition fraction
      within the extrathoracic regions are relatively small, but approach a factor of
      20 for deposition in the bronchial region. Deposition fractions for particles
      above 1 microm become very uncertain within the deeper regions of the lungs
      (bronchiolar and alveolar-interstitial).

PMID- 11569634
TI  - Preliminary uncertainty analysis for the doses estimated using the Techa River
      dosimetry system--2000.
AB  - The Mayak Production Association (MPA) was the first facility in the former
      Soviet Union for the production of plutonium. As a result of failures in the
      technological processes in the late 1940's and early 1950's, members of the
      public were exposed via discharge of about 10(17) Bq of liquid wastes into the
      Techa River (1949-1956). Residents of many villages downstream on the Techa River
      were exposed via a variety of pathways; the more significant included drinking of
      water from the river and external gamma exposure due to proximity to sediments
      and shoreline. The specific aim of this project is to enhance the reconstruction
      of external and internal radiation doses for individuals in the Extended Techa
      River Cohort. The purpose of this paper is to present the approaches being used
      to evaluate the uncertainty in the calculated individual doses and to provide
      example and representative results of the uncertainty analyses. The magnitude of
      the uncertainties varies depending on location and time of individual exposure,
      but the results from reference-individual calculations indicate that for external
      doses, the range of uncertainty is about a factor of four to five. For internal
      doses, the range of uncertainty depends on village of residence, which is
      actually a surrogate for source of drinking water. For villages with single
      sources of drinking water (river or well), the ratio of the 97.5th percentile-to
      2.5th percentile estimates can be a factor of 20 to 30. For villages with mixed
      sources of drinking water (river and well), the ratio of the range can be over
      two orders of magnitude.

PMID- 11569635
TI  - An experimental study on radiation streaming through a labyrinth in a proton
      accelerator facility of intermediate energy.
AB  - A radiation streaming experiment has been carried out at the Takasaki Ion
      Accelerator Facility for Advanced Radiation Application at the Japan Atomic
      Energy Research Institute in a room housing a Cu target irradiated with 68 MeV
      protons and in a labyrinth of three-legs having a total length of 29 m. In the
      experiment, neutron and gamma ray energy spectra, neutron reaction rates, and
      neutron and gamma ray dose equivalent rates were measured using various counters
      and dosimeters. The experimental data show the applicability of some empirical
      formulas for estimating the thermal neutron flux in a room and neutrons streaming
      in a labyrinth designed for a proton accelerator operating in the intermediate
      energy region. The data suggest that it is mandatory to estimate the gamma ray
      dose equivalent rate in a labyrinth, which is dominated by the secondary gamma
      rays due to the neutron capture reaction.

PMID- 11569636
TI  - New electron backscatter correction factors for accurate skin depth dose
      calculation from skin contamination by hot particles.
AB  - New backscatter correction factors have been calculated using the GEPTS Monte
      Carlo code system for the case of an isotropic electron point source located at
      the boundary of a semi-infinite water medium. The backscatter correction factor
      is defined as the ratio of the dose in a semi-infinite medium to the dose, at the
      same point, in an infinite medium. It is found that the backscatter correction
      factor variation with position inside the medium is significant. However, the
      backscatter correction factor variation with energy is quite small for electron
      energies less than 1 MeV. The backscatter correction factor data are tabulated
      for energies of 1, 2, 3, and 4 MeV as functions of radial distance and angular
      direction. The proposed backscatter correction factors can be used for skin depth
      dose calculations from beta particles emitted by either point sources or planar
      sources. Arbitrary target volumes and beta particle spectra can be considered.
      The new backscatter correction factors provide an alternative to the current data
      for accurate skin depth-dose calculations from skin contamination by hot
      particles.

PMID- 11569637
TI  - Analysis of an internal kinetic model for free and bound tritium.
AB  - Internal dosimetry models that currently drive regulatory compliance decisions
      assume that tritium retention kinetic behavior can be modeled by a single
      exponential function. This is contrary to the results of a number of modeling
      techniques, which indicate that while elemental tritium (HT) and tritiated water
      (HTO) are the most commonly released forms of tritium, organically-bound tritium
      (OBT) doses can be quite significant. In this paper, a unified two-compartment
      model of the retention kinetics of HTO and OBT is examined for the purpose of
      investigating the importance of metabolic routes not considered in the ICRP one-
      and two-exponent models; namely the transfer of tritium from the HTO compartment
      to the OBT compartment and vice versa. In particular, the effect of intake ratio
      is investigated, and a detailed analysis of dosimetric implications is performed.
      For typical combined intakes of HTO and OBT, the number of disintegrations from
      the two tritium forms can be roughly equal. This result, when combined with the
      suggested greater biological effectiveness of OBT, indicates effective doses will
      be greater than those obtained from a single exponential model. The results of
      this study corroborate previous findings using the two-compartment model for the
      cases of HTO-only and or OBT-only intakes and compare well with data taken from
      studies on animals and human subjects.

PMID- 11569638
TI  - Dietary intake of 210Po and 210Pb in the environment of Goa of south-west Coast
      of India.
AB  - This paper deals with the distribution and activity intake of 210Po and 210Pb in
      food, diet, and potable water samples of the Goa region and the estimated
      committed effective dose due to ingestion of these radionuclides. The activity
      concentrations of 210Po and 210Pb were determined in about 30 food and diet
      samples from different places of Goa in order to know the distribution and intake
      of these radionuclides. The activity concentration of 210Po in fish and prawn
      samples were significantly higher than concentrations found in vegetable and rice
      samples. Higher concentrations of 210Po and 210Pb were observed in leafy
      vegetables than in non-leafy vegetables. Among the diet samples the activity
      concentrations of 210Po and 210Pb in non-vegetarian meal samples were relatively
      higher than in vegetarian meal and breakfast samples. The committed effective
      dose due to annual intake of 210Po was found to be 94.6 microSv, 49.1 microSv,
      10.5 microSv, and 2.2 microSv and that of 210Pb found to be 81.6 microSv, 59.9
      microSv, 14.6 microSv, and 2.0 microSv for the ingestion of non-vegetarian meal,
      vegetarian meal, breakfast, and potable water, respectively.

PMID- 11569639
TI  - Early dose assessment in criticality accidents.
AB  - Early estimation of dose is useful in the medical evaluation of severe radiation
      accidents. In a prior publication, lymphocyte depletion kinetics were shown to
      follow an exponential decline for gamma accidents in which the average whole-body
      dose was in the range 50 cGy < D < 8-10 Gy. In that study, the depletion rate
      constant was linearly related to dose, within the statistical variation of the
      historical hematological data. This simple technique has now been extended to
      include analysis of various types of criticality accidents (liquid process; water
      moderated systems; metallic systems). Lymphocyte depletion in high-level mixed
      gamma/neutron accidents is found to be approximately equal, at a given effective
      dose, to that for gamma accidents. This universality would indicate a neutron RBE
      for human lymphocytes close to unity. Furthermore, the technique appears to be
      insensitive to the shape of gamma and neutron spectra, therefore making it
      especially robust for initial, approximate dose estimation.

PMID- 11569640
TI  - Proposed revision of the ICRP model for inhaled mercury vapor.
AB  - A critical review of the literature on the biokinetics of inhaled mercury vapor
      was performed as part of an accident analysis for the Spallation Neutron Source
      to be built at Oak Ridge National Laboratory. It was concluded that current
      models for inhaled mercury vapor do not accurately describe the distribution or
      residence time of mercury deposited in the respiratory tract. This paper proposes
      a model that is more consistent with collective information on the fate of
      inhaled mercury vapor in laboratory animals and human subjects. Compared with the
      model currently recommended by the International Commission on Radiological
      Protection (ICRP), the proposed model predicts lower deposition in the bronchi
      and bronchioles, greater deposition in the alveolar-interstitial region, and a
      different pattern of absorption to blood. The proposed model yields substantially
      reduced estimates of lung dose and effective dose for most radioisotopes of
      mercury inhaled as mercury vapor.

PMID- 11569641
TI  - Does longevity in beagles injected with bone-seeking radionuclides depend upon
      radiation dose in the absence of known radiation effects?
AB  - Regression analyses of longevity as a function of skeletal radiation dose among
      groups of beagles injected with 226Ra, 228Ra, 228Th, 241Am, 90Sr or monomeric
      239Pu suggested that at low doses and dose-rates (those at which induced effects
      are low), age at death seems to be independent of dose when animals dying with
      specific radiation effects were excluded, although longevity does appear to be a
      function of dose when animals dying with established radiation effects and at all
      doses were included. We conclude tentatively that, for mammals receiving skeletal
      dose from bone-seeking radionuclides at low doses and low dose-rates, longevity
      may not be dependent upon skeletal radiation dose in the absence of radiation
      induced malignancies or other radiation effects.

PMID- 11569642
TI  - Uranium bioassay--beyond urinalysis.
AB  - Assessment of occupational or environmental exposure to uranium compounds is
      largely based on urinalysis. However, urine samples generally reflect either
      recent exposure (within a few days after an incident) or chronic exposure and,
      furthermore, diurnal fluctuations in "spot samples" make it difficult to estimate
      the extent of the internal dose received. Thus, if urine samples are not
      collected within a relatively short time after accidental exposure or if the
      samples are not representative due to collection logistics, internal dosimetry
      calculations based only on urinalysis may be misleading. With the advent of
      efficient and sensitive methods for determination of uranium in hair and nails,
      some of these drawbacks may be overcome. It is proposed that with little
      additional cost, determination of the uranium in hair may yield better insights
      for internal dosimetry of uranium exposure.

PMID- 11569643
TI  - Comments on "An evaluation of the ethical principles of the ICRP's radiation
      protection standards for workers".

PMID- 11569644
TI  - The apparent endocrine effects of non-ionizing radiation: a new consideration in
      determining exposure standards.

PMID- 11569646
TI  - Cumulative indexes, volumes 31-50.

PMID- 11569645
TI  - U.S. French bilateral R&D agreement.

PMID- 11569647
TI  - A pilgrim's progress: my urogynecological quest.

PMID- 11569648
TI  - Conservative treatment of stress incontinence with Geisha balls.
AB  - In a pilot study 6 women with stress urinary incontinence were treated with
      Geisha balls while performing pelvic floor muscle exercises at home half an hour
      a day for 12 weeks. Subjectively 4 patients were cured and 2 had improved. Before
      the treatment the 24-hour pad test was a mean 48 g and after the treatment a mean
      10 g. There were no adverse effects.

PMID- 11569649
TI  - The epidemiology of overactive bladder among females in Asia: a questionnaire
      survey.
AB  - A questionnaire-based survey was performed in 5502 females from 11 countries in
      Asia to establish the prevalence overactive bladder (OAB) and identify the
      factors related to the occurrence of the condition. The overall prevalence of OAB
      was 53.1%. The most common presenting symptom was urgency (65.4%). Twenty-one per
      cent of the OAB population presented with incontinence, giving an overall
      prevalence of 11.4% for urge incontinence among Asian females. The majority
      (75.4%) were not significantly bothered by the condition. Only 21.1% sought
      treatment. Older age, multiparity, a positive family history, residence in a
      rural area and the use of a sitting type of toilet were found to be associated
      with a greater occurrence of OAB. The study has shown that overactive bladder in
      Asian females is significant and warrants closer attention. It has also
      highlighted the low treatment-seeking rate among its sufferers. This is the first
      report on the epidemiology of overactive bladder among Asians in the medical
      literature.

PMID- 11569650
TI  - Irritative symptoms after colposuspension: are they due to distortion or
      overelevation of the anterior vaginal wall and trigone?
AB  - Symptoms of bladder irritability are common after incontinence surgery but their
      cause is unknown. This study tests the hypothesis that irritative symptoms after
      colposuspension are due to distortion of the trigone. As part of longitudinal
      follow-up studies, 175 women were examined 6 months to 12 years after either an
      open or a laparoscopic Burch colposuspension. The main outcome measures were
      symptoms of bladder irritability (frequency, nocturia and urge incontinence) and
      ultrasound findings (bladder neck position at rest and on Valsalva, the presence
      of a colposuspension ridge, ridge depth and ridge distance, and trigonal angle).
      Two positive associations between ultrasound parameters and symptoms of bladder
      irritability were observed: urge incontinence was more likely in the presence of
      bladder neck funneling, and women with nocturia had a higher trigonal angle.
      Increased distortion of the trigone was associated with a reduced incidence of
      urge incontinence in the subgroup of patients after laparoscopic colposuspension.
      The data presented in this study do not support the hypothesis that symptoms of
      bladder irritability are due to trigonal distortion or overelevation.

PMID- 11569651
TI  - Risk factors for an elevated postvoid residual urine volume in women with
      symptoms of urinary urgency, frequency and urge incontience.
AB  - The aim of this study was to identify factors in patients with symptoms of
      urgency/frequency or urge incontinence that predict that the postvoid residual
      urine volume (PVR) will be elevated. A restrospective chart review was carried
      out of all patients new to our urogynecology practice between June 1998 and May
      1999, with symptoms of urgency, frequency and/or urge incontinence. Demographic
      variables, symptoms and physical findings were correlated with the presence of an
      elevated PVR (>100 ml) using logistic regression analysis. An elevated PVR was
      found in 10% (33/336) of patients with urge incontinence (UI). and in 5% (3/57)
      of patients with urgency/frequency without UI. In patients with UI the presence
      of pelvic organ prolapse (POP) > or = stage II, symptoms of voiding difficulty
      and the absence of the symptom of stress incontinence, predicted 82% of patients
      with an elevated PVR.

PMID- 11569652
TI  - Doppler velocimetry parameters of periurethral vessels in postmenopausal
      incontinent women receiving estrogen replacement.
AB  - Estrogen deficit causes significant alterations in the lower urinary tract of
      women, largely affecting urinary continence mechanisms. The urethral vascular bed
      accounts for about one-third of urethral pressure, and as it undergoes marked
      hormonal influence we became interested in investigating its behaviour both prior
      to and during estrogen replacement. We selected 25 postmenopausal patients with
      urinary stress incontinence and studied the periurethral vessels by means of
      Doppler velocimetry, analyzing the number of vessels, systolic peak, minimum
      diastole, resistance and pulsatility indexes and the A/B ratio, prior to estrogen
      replacement and after 1 and 3 months of hormone use. We concluded that estrogen
      replacement alone in postmenopausal women with urinary stress incontinence
      increased the number of periurethral vessels, systolic peak and minimum diastole;
      however, a trend of no statistical significance towards the reduction of
      resistance and pulsatility rates of periurethral vessels was found; nor was a
      significant difference in the A/B ratio shown.

PMID- 11569653
TI  - Poor surgical outcomes after fascia lata allograft slings.
AB  - The objective of this retrospective case control study was to determine whether
      our poor surgical outcomes were associated with the material used to construct
      our pubovaginal slings. Autologous rectus fascia was used in 33 patients and
      cadaveric fascia lata was used in 12 patients who underwent pubovaginal sling
      placement for intrinsic urethral sphincter deficiency (ISD). Treatment was
      successful in 78.8% and 33.3% of patients who underwent rectus fascia and fascia
      lata allograft slings, respectively (P=0.006). Based on regression analysis, the
      sling material was found to be strongly associated with surgical outcome after
      controlling for all confounding variables (beta coefficient = 1,204.6,
      P<0.00005). We conclude that fascia lata allografts are a poor choice for
      pubovaginal slings.

PMID- 11569654
TI  - Antibiotic treatment to prevent urinary tract infections after urodynamic
      evaluation.
AB  - The aim of the study was to determine the efficacy of cotrimoxazole
      administration after urodynamic testing to prevent urinary tract infections. In a
      single-blind prospective randomized study 94 women who attended for urodynamic
      evaluation were included. After multichannel urodynamic testing, including two
      catheterizations, the women received a single dose of cotrimoxazole or placebo. A
      clean-catch urine specimen was tested for infection after 1 week. Seventy women
      returned a urine specimen after 1 week: 2/37 (5.4%) in the treatment and 2/33
      (6.1%) in the placebo group had acquired a new urinary tract infection after
      urodynamics. One major and one minor adverse reaction to cotrimoxazole were
      reported. The power of the sample size was unfortunately too small to draw
      conclusions as to the efficacy of prophylaxis.

PMID- 11569655
TI  - The role of estrogen supplementation in lower urinary tract dysfunction.
AB  - The female lower urinary and genital tracts both arise from the primitive
      urogenital sinus and develop in close anatomical proximity. Sex hormones have a
      substantial influence on the female lower urinary tract throughout adult life,
      with fluctuations in their level leading to macroscopic, histological and
      functional changes. Urinary symptoms may therefore develop during the menstrual
      cycle, in pregnancy and following the menopause. Estrogen deficiency,
      particularly when prolonged, is associated with a wide range of urogenital
      complaints, including frequency, nocturia, incontinence, urinary tract infections
      and the 'urge syndrome'. Estrogen supplementation subjectively improves urinary
      stress incontinence but there is no objective benefit when given alone; however,
      estrogen given in combination with phenylpropanolamine may be clinically more
      useful. Hormone replacement therapy does appear to treat postmenopausal
      irritative urinary symptoms such as frequency and urgency, possibly by reversing
      urogenital atrophy, and there is also evidence to suggest that estrogens can
      provide prophylaxis against recurrent urinary tract infections. However, the
      'best' type of estrogen, route of administration and duration of therapy are at
      present unknown.

PMID- 11569656
TI  - Retropubic urethropexy (Burch colposuspension).
AB  - Many varied procedures have been described for the surgical treatment of female
      stress incontinence. Over the years these have had enthusiastic proponents, but
      not until the recent publication of two systematic literature reviews did their
      relative efficacies become apparent. At present it would appear that open
      suprapubic urethropexy is the current 'gold standard' procedure. Many new minimal
      access techniques aimed at reducing the morbidity of a Burch colposuspension have
      been proposed. However, careful analysis of the medium- to long-term success of
      these procedures and their associated complications is needed before they are
      adopted universally.

PMID- 11569657
TI  - Urodynamic techniques.
AB  - Appropriate investigation is essential to a full evaluation of any patient with
      urinary incontinence, as accurate diagnosis leads to correct treatment. This
      paper describes the various investigations for lower urinary tract dysfunction,
      and their main indications. They include the pad test, uroflowmetry, subtracted
      cystometry, and more complex investigations such as videocystourethrography,
      ambulatory urodynamics, urethral pressure profilometry, magnetic resonance
      imaging and electromyography. Although not every patient requires extensive
      investigation, appropriate use of tests of lower urinary tract function provides
      useful information on which to base appropriate treatment.

PMID- 11569658
TI  - Pharmacological management of detrusor instability.
AB  - Urinary incontinence and lower urinary tract dysfunction remain an important
      cause of morbidity, affecting at least 14% of women over the age of 30 years.
      Whilst the etiology and pathophysiology of detrusor instability remains to be
      elucidated drug therapy remains important in the management of women with the
      irritative symptoms of urgency, frequency and urge incontinence. The number of
      drugs which have been developed illustrates the point that none are ideal, often
      having systemic adverse effects limiting their therapeutic usage and affecting
      compliance. This review aims to assess the current pharmacological management of
      detrusor instability as well as examining recent progress in the development of
      new agents, some of which may prove to be efficacious.

PMID- 11569659
TI  - Posthysterectomy vault eversion with a large retroperitoneal mass.
AB  - A woman with complete vaginal eversion was found to have a large pelvic mass,
      extending from the rectovaginal septum to the presacral space. This 66-year-old
      woman with posthysterectomy vaginal eversion complained of pelvic fullness. A
      pessary provided relief of the prolapse, but the symptom of fullness persisted.
      Physical examination did not identify a pelvic mass. Computed tomography (CT) and
      magnetic resonance imaging (MRI) demonstrated a 9 cm tumor of the rectovaginal
      septum, extending to the presacral space. At laparotomy the patient had a massive
      neurofibroma arising from the anterior rectal wall. This case is of interest
      because the complete vaginal prolapse obscured the diagnosis of this large pelvic
      tumor. CT and MRI were useful in identifying and characterizing the mass. To our
      knowledge, this is the first reported case of vaginal prolapse with a large
      pelvic mass.

PMID- 11569660
TI  - Transurethral suture cystorrhaphy for repair of vesicovaginal fistulas: evolution
      of a technique.
AB  - Technical difficulties in the initially described transurethral repair of
      vesicovaginal fistulas have led to several modifications in technique. In an
      uncontrolled trial, these modifications included the use of a suprapubic tract,
      along with an arthroscope for visualization of the fistula. A large-caliber port
      is passed per urethram for transurethral instrumentation access. New-generation
      laparoscopic needle driver technology markedly improves the ease of transurethral
      suturing. Three previously unreported vesicovaginal fistula patients have had
      successful resolution of their fistulas after undergoing transurethral repair.
      Small-diameter vesicovaginal fistulas in selected patients can be successfully
      repaired by a minimally invasive transurethral suture technique.

PMID- 11569661
TI  - An ART field study in western Nepal.
AB  - AIM: To evaluate the effectiveness of three different types of glass ionomer
      restorations placed in children's teeth using the ART technique two years after
      placement by either dentists or primary health care workers. SETTING: The rural
      district of Palpa in western Nepal. METHOD: An opportunistic non-randomised field
      study, commenced in April 1997. Three different glass ionomer restorative cements
      were used: Fuji IX (GC), Dentsply Baseline (DENTSPLY/DeTrey), and S.S. WhiteR
      (S.S. White). The restorations were assessed two years later by an independent
      evaluator, who was blind to the type of restorations used and also blind to the
      operators. RESULTS: Four primary health care workers and two dentists restored
      163 primary and permanent teeth using hand instruments. One and two surface
      restorations were placed in 105 students ranging from 3 to 19 years of age from
      seven schools. After two years, 79 (75%) of the restorations survived and 27
      (25%) failed, while 100% of 21 evaluated single surface restorations placed on
      permanent molars with Fuji IX survived. There was no statistically significant
      difference in the survival of the restorations placed by dentists and placed by
      primary health care workers, which corroborates that both groups are both capable
      of performing the technique satisfactorily. CONCLUSIONS: ART is very effective
      for one surface permanent molars using improved glass ionomer cements designed
      for the ART technique.

PMID- 11569662
TI  - Reasons for placement and replacement of amalgam restorations in Jordan.
AB  - AIMS: To record the reasons for placement and replacement of amalgam restorations
      in Jordan, to determine the use of amalgam restorations in common cavity types
      and to collect data on the age of the replaced amalgam restorations. SUBJECTS AND
      SETTING: Dentists in Jordan (n=241). METHOD: Cross-sectional study using postal
      survey backed up with personal contact. Data was recorded for all restorations
      placed or replaced over a period of one month. RESULTS: Information was collected
      on 3,166 restorations from patients aged 9 to 66 years. Of all restorations,
      54.8% were first time placements while 45.2% were replacements of old
      restorations. The major reason for the first time restorations was primary
      caries, while that for replacement was secondary caries (28.5%) followed by
      broken and lost restorations (20.4%), root canal therapy (17%), tooth fracture
      (12%), pain or sensitivity (8.8%), poor margins (8.5%). CONCLUSIONS: In Jordan,
      the main reason for first placement of amalgam restoration is primary caries, the
      main reason for replacement is secondary caries.

PMID- 11569663
TI  - Intervals for oral health examinations among Finnish children and adolescents:
      recommendations for the future.
AB  - AIM: To review the frequency of routine annual dental examinations for children
      in Finland and to make recommendations for appropriate examination intervals for
      children and adolescents. METHOD: The National Research and Development Centre
      for Welfare and Health in Finland appointed an expert group to prepare a review.
      RESULTS: According to the literature, examination intervals for individuals with
      low caries risk can be extended to 1.5-2.0 years without jeopardising their oral
      health. If implemented, this would lead to a saving of 15% in treatment and
      examination times for children. Although there is no accurate measure for
      identifying high-risk individuals, a considerable proportion of low-risk children
      can be identified fairly accurately. CONCLUSIONS: The expert group recommended
      prolonging the average examination intervals to 1.5-2.0 years, taking into
      account the risk of each individual, the local distribution of oral health
      problems and cost-effective use of resources. Part of the savings could be
      redirected to children with high levels of dental need and/or at risk of dropping
      out from the oral health services.

PMID- 11569664
TI  - Dental fear among a young adult Saudian population.
AB  - AIMS: To assess the prevalence of dental fear and reasons for irregular dental
      attendance among young adult university students; to describe the gender
      distribution of the dentally anxious population according to the perceived
      origins or sources of fear; to identify the time of fear development and
      preference for anaesthesia or sedation before dental treatment. METHOD: A
      questionnaire incorporating the Dental Fear Scale (DFS) with items related to
      sources of dental fear stimuli, together with the preference of anaesthesia or
      sedation before dental treatment and other characteristics. Approximately 500
      questionnaires were distributed among Saudian undergraduate students. RESULTS:
      368 questionnaires were completed and presented for statistical analysis. The
      sight and sensation of anaesthetic needles and the sight, sound and sensation of
      the drill were rated the most fear-eliciting stimuli. Also, females tended to be
      more anxious than males. Increased heart rate was the most common reported
      physiological response to fear resulting from dental treatment. The overall level
      of fear of dental work among the studied population was found to be about
      39%.'Lack of time' and 'no need for treatment' were found to be the main reasons
      for irregular dental visits. Fear of pain and trauma were the major perceived
      sources of reported fear reactions and were developed mainly during childhood.
      About 63% of the subjects preferred to have local anaesthesia before dental
      treatment to prevent or ameliorate dental fear.

PMID- 11569665
TI  - Needs and demands for dental care in patients attending the University Dental
      Hospital in Sri Lanka.
AB  - AIMS: To determine the needs and demands for dental care in patients visiting a
      university dental hospital. DESIGN: A cross-sectional study of first visit
      patients. SETTING: The University Dental Hospital in Peradeniya, Sri Lanka.
      PARTICIPANTS: A total of 849 first visit patients. METHODS: The main complaint of
      each patient was recorded and was considered as a measure of demand for dental
      care. Tooth based and orthodontic treatment needs were assessed using the WHO
      basic methods. Periodontal treatment need was assessed by the periodontal
      treatment needs system. Need for prosthetic care was also assessed. RESULTS:
      Thirty per cent and 23% of patients demanded treatment for decayed teeth and
      toothache respectively. Nearly 34%, 27% and 17% of patients needed surgical,
      restorative and periodontal care respectively for the main complaint. Of those
      seeking care, 94% needed treatment other than what was required for the main
      complaint. The predominant normative treatment need was for periodontal care
      (77%) whilst 47% needed restorations or extractions. CONCLUSION: Normative needs
      of patients demanding treatment were high and many had demanded treatment before
      acute symptoms had developed. However, delays in seeking care were evident.
      Further studies are needed to identify factors for delay in obtaining care.

PMID- 11569666
TI  - Dental experience of cleft affected children in the west of Ireland.
AB  - AIM: To investigate caries experience and initial access to dental services in a
      group of children with cleft lip/palate in the west of Ireland. DESIGN AND
      METHOD: Cross sectional study with prospective data capture and matched control.
      Details of children born with a cleft were obtained from all health professionals
      likely to be involved in delivering care to these children. Existing databases
      were cross-referenced to eliminate duplication or missed patients. A matched
      control sample was recruited from 14 schools in the region. RESULTS: A sample of
      90 cleft affected children (48 male, 42 female) with any category of cleft born
      between 1980-1996 (i.e. 16 years) was compared with a control group of 100 non
      cleft children (60 male, 40 female). The DMF index was determined by a trained
      and calibrated clinician. Twenty-two percent (n=20) of the cleft group were
      caries free compared to 41% (n=41) in the control group. The combined dmf/DMF for
      the cleft group was 2.09 compared to 1.50 for the control (P<0.05). Separate
      analysis of the dmf and DMF between the two groups indicated that the difference
      lay in the caries found in the deciduous dentition of the cleft group. The first
      dental visit was at 4 years of age for the cleft group. CONCLUSIONS: Cleft
      affected children in the region did not receive adequate and regular dental care
      at the appropriate time. In view of the significantly greater risk of dental
      disease in clefting, particularly in the deciduous dentition, all cleft affected
      children should be referred for comprehensive and continued preventive dental
      care from the first year of life.

PMID- 11569667
TI  - Differences in dimensions of satisfaction with private and public dental care
      among children.
AB  - Measures of patient satisfaction have application in understanding patient
      behaviour, and in evaluating dental providers, services, and facilities. Further,
      differences in delivery systems may be reflected in variation between the
      component dimensions of satisfaction. AIM: The aim of this study was to compare
      perceptions of satisfaction with care provided by the School Dental Service (SDS)
      and private dentists. DESIGN: A three-stage cross-sectional survey was conducted
      during 1993-94. This analysis is based on Stage 2 of the study (n=2,792
      participants, response rate=78.0%). SETTING: Schools in metropolitan Adelaide,
      South Australia. PARTICIPANTS: Parents and schoolchildren. INTERVENTIONS/METHODS:
      Mailed self-complete questionnaires. MAIN OUTCOME MEASURES: The Dental
      Satisfaction Index (DSI) and component subscales. RESULTS: Overall satisfaction
      using the DSI showed no significant difference between SDS users and users of
      private dental care. Parents of children using the SDS had lower satisfaction
      scores for 'general satisfaction', 'quality', 'access', and 'continuity', but had
      higher satisfaction scores for the dimensions of 'cost' and 'availability' (OLS
      regression; P<0.01). These patterns of satisfaction with dental care by provider
      group persisted after controlling for time since last visit, parental education
      level, insurance status, occupation and language spoken (OLS regression; P<0.05).
      This may reflect a counter-balancing of dimensions of satisfaction across
      provider groups resulting in no significant difference in the DSI. CONCLUSIONS:
      Overall satisfaction was high and did not vary by provider group, but there was
      variation in the component dimensions of satisfaction.

PMID- 11569668
TI  - The relationship between sweetness preference and dental caries in mother/child
      pairs from Maringa-Pr, Brazil.
AB  - AIM: Children's patterns of sugar consumption and dental health status have been
      associated to their mothers' patterns. As a liking for sweetness has been related
      to caries levels, this study was carried out to analyse the relationship between
      sweetness preference and caries experience in mother/child pairs. PARTICIPANTS
      AND METHODS: A cross-sectional survey was conducted on a sample of low socio
      economic mothers and their 4-5-year-olds from Maringa-Pr, Brazil. Mothers' and
      children's preference for sugar was measured using the Sweet Preference
      Inventory. Their caries experience was assessed according to World Health
      Organization (WHO) guidelines. RESULTS: High levels of sweetness preference and
      caries experience were found in the sample studied. Although not strong, a
      significant correlation in patterns of sweetness preference (r=0.12, P<0.05) and
      caries experience (r=0.14, P<0.05) between mother/child pairs was identified.
      Among the social-demographic variables, only family income was statistically
      associated with the children's preference for sweetness (P<0.05). No significant
      association between sweetness preference and caries experience could be
      established. CONCLUSION: The findings of this study suggest that mothers may play
      an important role on the establishment of their children dietary preferences and
      patterns of dental health. Also, that the socio-economic status may influence
      children's preference for sugar.

PMID- 11569669
TI  - Prevalence of ocular injuries, conjunctivitis and use of eye protection among
      dental personnel in Riyadh, Saudi Arabia.
AB  - AIMS: To find out the prevalence of ocular injury and infection among dental
      personnel in Riyadh, Saudi Arabia. PARTICIPANTS: Two hundred and four dental
      personnel. METHOD: A questionnaire completed by researchers and observation
      during practice. RESULTS: The response rate was 81%. Dentists and dental
      technicians had a similar prevalence (42.3%) of foreign bodies in their eyes
      during the period of one month. Almost 50.5% of dentists rarely had foreign
      bodies in their eyes, while only 22.2% of dental technicians claimed the same.
      The majority of dental surgery assistants (73.6%) never experienced foreign
      bodies in their eyes. Only 27.0% of female personnel had foreign bodies in their
      eyes as compared to 73.0% of male personnel, while only 28.5% of females had
      conjunctivitis as compared to 71.4% among male personnel. 75% of regular eye
      protector wearers (EPW) never had foreign bodies while 67.2% EPW never had
      conjunctivitis. Dental technicians were more prone to ocular injury, 13.8% as
      compared to 4.4% of dentists. Only 30% of the regular eye protector wearers
      suffered ocular injury. CONCLUSIONS: Protection of the eyes should be emphasised
      and practised at undergraduate level. The awareness of eye protection should be
      highlighted at all clinical and research symposia. Further studies should be
      conducted to assess the financial implications of ocular injuries and infections
      in dental institutions and practices. Recommendations are made for universal
      precautions and the observation of safety at work guidelines by all dental team
      members.

PMID- 11569671
TI  - Transient lower esophageal sphincter relaxations: how many or how harmful?

PMID- 11569670
TI  - Oral health status and oral health behaviour of urban and rural schoolchildren in
      Southern Thailand.
AB  - AIM: To describe the level of oral disease in urban and rural schoolchildren in
      Southern Thailand; to analyse self-care practices and dental visiting habits of
      12-year-olds, and to assess the effect of socio-behavioural factors on dental
      caries experience. DESIGN: A cross sectional study of 6- and 12-year-old
      children, urban and rural schools chosen at random from 19 districts of one
      province. SETTING: Suratthani Province, Southern Thailand. PARTICIPANTS: A total
      of 1,156 children of grade 1 (6 yrs) and 1,116 children of grade 6 (12yrs).
      METHODS: Clinical recordings of dental caries and periodontal CPI scores 0, 1 or
      2 according to WHO; structured interviews of 12-year-olds (n=1,084) concerning
      oral health behaviour and attitudes. RESULTS: At age 6, 96.3% of children had
      caries and mean dmft was 8.1. In 12-year-olds, 70% had caries in permanent teeth
      and the level of DMFT was 2.4. Experience of pain during the previous 12 months
      was reported by 53% of 12-year-olds, 66% saw a dentist within the previous year
      and 24% reported that visits were due to troubles in teeth. Toothbrushing at
      least once a day was claimed by 88%. Significant numbers of the children reported
      having hidden sugar every day: soft drinks (24%), milk with sugar (34%), and tea
      with sugar (26%). Important predictors of high caries experience were dental
      visits, consumption of sweets, ethnic group (Muslim) and sex (girls) whereas
      lower risk was observed in children with positive oral health attitudes.
      CONCLUSIONS: Systematic health education may further improve the oral health of
      Thai children and the primary school provides a unique setting for such
      programmes.

PMID- 11569672
TI  - Adenocarcinoma of the pancreas: is surgery making a difference?

PMID- 11569673
TI  - Betaine: an old therapy for a new scourge.

PMID- 11569674
TI  - Idiopathic acute recurrent pancreatitis.
AB  - Acute recurrent pancreatitis (ARP) results most commonly from alcohol abuse or
      gallstone disease. Initial evaluation fails to detect the cause of ARP in 10-30%
      of patients, and as a result the diagnosis of "idiopathic" ARP is given. In these
      patients, a more extensive evaluation including specialized labs, ERCP,
      endoscopic ultrasound, or magnetic resonance cholangiopancreatography typically
      leads to a diagnosis of microlithiasis, sphincter of Oddi dysfunction, or
      pancreas divisum. Less commonly, hereditary pancreatitis, cystic fibrosis, a
      choledochocele, annular pancreas, an anomalous pancreatobiliary junction,
      pancreatobiliary tumors, or chronic pancreatitis are diagnosed. Determining the
      etiology is important, as it helps to direct therapy, limits further unnecessary
      evaluation, and may improve a patient's long term prognosis.

PMID- 11569675
TI  - Percutaneous endoscopic gastrostomy and outcome in dementia.
AB  - The use of percutaneous endoscopic gastrostomy for the administration of food and
      medications in patients with dementia has been on an increase. Many studies have
      failed to demonstrate the positive outcome expected of this feeding modality for
      the indications that required tube placement. Hence, the concept of feeding
      through gastrostomy tubes has become the subject of much discussion and
      controversy in recent times. We have reviewed the literature with regard to
      outcome in older patients with dementia and percutaneous endoscopic gastrostomy
      with respect to nutritional parameters, quality of life, and survival. A brief
      discussion on ethical and legal aspects is included. Much of the data do not
      suggest that outcome in dementia is favorably improved after percutaneous
      gastrostomy.

PMID- 11569676
TI  - Etanercept in the treatment of active refractory Crohn's disease: a single-center
      pilot trial.
AB  - OBJECTIVES: Etanercept, an injectable tumor necrosis factor (TNF) receptor fusion
      protein, binds and inactivates human TNF and is used in active rheumatoid
      arthritis. Blocking TNF with monoclonal antibodies has also been beneficial in
      Crohn's disease. We attempted to determine the efficacy and safety of etanercept
      for induction of clinical, endoscopic, and histological improvement in patients
      with moderate to severe Crohn's disease despite standard treatment. METHODS: Ten
      patients with active Crohn's disease were treated with etanercept (25 mg s.c.)
      twice per week for 12 wk. Background therapy was kept stable during the trial.
      Crohn's disease activity index (CDAI), Inflammatory Bowel Disease Questionnaire,
      and C-reactive protein levels were measured at weeks 0, 2, 4, 8, and 12.
      Colonoscopies were performed before and after therapy in responders; endoscopic
      biopsies were scored for inflammation. RESULTS: At week 2 after the start, a
      clinical response (deltaCDAI > or = 70) was observed in 6/10 patients (median =
      305 [294-418] to 166 [107-392]), with reduction in serum C-reactive protein
      levels (median = 17.2 [6.8-67.2] to 9.1 [0.9-17.2] mg/dl). Colonoscopies showed a
      reduction in inflammatory lesions in the four patients who attained remission
      (CDAI < 150), whereas the inflammatory score of the biopsies did not decrease
      significantly. No moderate or severe adverse events were observed. CONCLUSIONS:
      Etanercept may be effective in Crohn's disease refractory to standard therapy.

PMID- 11569677
TI  - Transient lower esophageal sphincter relaxations are no more frequent in patients
      with gastroesophageal reflux disease than in asymptomatic volunteers.
AB  - OBJECTIVES: Studies of the relative frequency of transient lower esophageal
      sphincter relaxations (TLESRs) in patients with gastroesophageal reflux disease
      and asymptomatic controls have revealed conflicting data. We have therefore
      studied the frequency of TLESRs and the frequency and mechanisms of acid reflux
      episodes in patients with gastroesophageal reflux disease and age- and sex
      matched asymptomatic controls using standardized criteria. METHODS: Ten patients
      with symptomatic gastroesophageal reflux disease (four male, aged 50 [30-59] yr)
      and 10 asymptomatic matched volunteers (four male, aged 50 [32-59] yr) were
      studied. Esophageal, lower esophageal sphincter, and gastric manometric and
      esophageal pH readings were recorded for 1 h before and 1 h after a 200-kcal, 150
      ml long-chain triglyceride meal. RESULTS: TLESR frequency increased after the
      meal in both volunteers (median 0 [range = 0-3] to 3 [0-8] per hour,p < 0.01) and
      patients (1 [0-6] to 2.5 [0-9] per hour, p = 0.08). There was no significant
      difference in the frequency of TLESRs between volunteers and patients. TLESRs
      were more likely to be associated with acid reflux in patients (65% vs 37%, p =
      0.03), whereas volunteers were more likely to reflux gas or liquid without acid
      (30% vs 3.0%, p = 0.01). CONCLUSIONS: TLESRs are no more frequent in patients
      with gastroesophageal reflux disease than age- and sex-matched asymptomatic
      volunteers. However, when TLESRs occur in patients, they are twice as likely to
      be associated with acid reflux.

PMID- 11569678
TI  - Esophageal mucin: an adherent mucus gel barrier is absent in the normal esophagus
      but present in columnar-lined Barrett's esophagus.
AB  - OBJECTIVES: The presence of a protective adherent mucus gel barrier against
      gastric reflux in the healthy esophagus is uncertain. The aim was to characterize
      the surface mucin composition and determine the extent of any adherent mucus gel
      layer on the normal esophagus, and compare this with that in Barrett's esophagus.
      METHODS: Isolated surface mucins were characterized by density centrifugation,
      gel filtration chromatography, and chemical composition. Adherent surface mucus
      was visualized in situ on unfixed and cryostat sections of mucosa and biopsies
      using a method that preserves mucus layer thickness. RESULTS: There was a
      complete absence of adherent mucus gel layers on normal human, pig, and rat
      esophagi. This was in contrast to the thick adherent mucous layer (median
      thickness = 100-200 microm) seen on the corresponding gastric mucosa. Small
      quantities of glycoprotein with a composition characteristic of a secretory mucin
      were isolated from the pig esophagus surface. The mucin, density range between
      1.44 and 1.48 g x ml(-1), contained 80% carbohydrate and was rich in serine,
      threonine, and proline. The mucin fragmented into smaller glycoprotein units on
      proteolysis and partially on reduction. Cryostat sections from columnar-lined
      esophageal biopsies had a substantial adherent surface mucous layer (median
      thickness = 90 microm, interquartile range = 84-94 microm) staining for neutral
      mucins (gastric-type epithelium) and acidic mucins (intestinal metaplasia).
      CONCLUSIONS: A secretory mucin, with an analysis distinct from that of gastric or
      salivary mucin, is present in very small quantities on the esophageal mucosa and
      in amounts insufficient to form an adherent gel layer. It is unlikely that mucus
      has a role in protecting the normal esophagus against reflux. However, an
      adherent mucous layer was observed over columnar-lined esophagus, and this may
      protect against reflux.

PMID- 11569679
TI  - Functional chest pain of esophageal origin: hyperalgesia or motor dysfunction.
AB  - OBJECTIVE: Many patients with functional (noncardiac) chest pain exhibit both
      hypersensitivity and motor dysfunction of the esophageal wall. We aimed to
      determine whether the sensory or motor dysfunction plays an important role in the
      pathogenesis of chest pain. METHODS: We performed graded balloon distentions of
      the esophagus using impedance planimetry in 16 consecutive patients with chest
      pain and otherwise normal cardiac and esophageal evaluations and in 13 healthy
      controls. In those patients who experienced chest pain with balloon distention,
      the test was repeated after atropine was given. Sensory and biomechanical
      parameters were measured. RESULTS: Balloon distention reproduced typical chest
      pain in 13/16 patients (81%) and at lower (p < 0.01) sensory thresholds than
      controls. Pain was reproduced in all 13 patients and at lower (p < 0.05) sensory
      thresholds after atropine. Also, after atropine, the esophageal cross-sectional
      area and wall tension increased (p < 0.05), the tension/strain association
      shifted to the right (p < 0.05), and reactivity decreased (p < 0.002) relative to
      results before atropine or in healthy controls (i.e., the esophageal wall relaxed
      and became more deformable). CONCLUSIONS: Even after relaxing the esophageal
      wall, most patients experienced chest pain and at lower sensory thresholds.
      Hence, hyperalgesia rather than motor dysfunction appears to be the predominant
      mechanism for functional chest pain of esophageal origin.

PMID- 11569680
TI  - Esophageal hyperalgesia in patients with ulcerative colitis: role of experimental
      stress.
AB  - OBJECTIVES: Intestinal inflammation is associated with enteric nervous system
      alterations, at both inflamed and noninflamed sites. The perception of stimuli
      from the GI tract is enhanced during inflammatory conditions, but it is unknown
      whether visceral hypersensitivity is limited to the inflamed area or diffuse
      throughout the entire GI tract. Moreover, although stress can reactivate
      inflammatory processes in the gut, it is unknown if this can alter perception
      from the GI tract. Our aim was to determine if patients with ulcerative colitis
      (UC) have increased esophageal sensitivity to distention and whether this is
      modified by experimental stress. METHODS: Ten UC patients and 12 healthy
      volunteers (HVs) underwent gradual balloon distension of the esophagus to assess
      their visceral sensitivity. Perceptive and pain thresholds were evaluated in
      basal conditions and after induction of experimental stress (cold water pressure
      test) while blood pressure and heart rate were monitored. RESULTS: Patients with
      UC had perceptive thresholds to distension similar to HVs (14.8+/-2.0 ml of air
      vs 14.5+/-3.0 ml); in contrast, the volume increment needed to evoke pain was
      significantly lower in UC patients than in HVs (58.9% vs 149.9%, p < 0.05).
      Physical stress caused a similar decrease in perceptive thresholds in HVs (
      29.1+/-8.4%) and patients (-17.7+/-9.1%), but pain thresholds were significantly
      decreased only in HVs (-28.3+/-7.1% vs -11.5+/-12.3%). CONCLUSIONS: UC is
      characterized by increased esophageal sensitivity, indicating the existence of
      diffuse hyperalgesia during intestinal inflammatory processes. This increased
      sensitivity may account for the frequent upper GI symptoms these patients
      complain of when in clinical remission.

PMID- 11569681
TI  - Chemospecific alterations in duodenal perception and motor response in functional
      dyspepsia.
AB  - OBJECTIVE: Abnormal gastroduodenal motility and visceral hypersensitivity to
      intraduodenal acid have recently been recognized as pathophysiological factors in
      functional dyspepsia. The aim of this study was to assess whether these
      abnormalities in functional dyspepsia depend on the chemical composition of the
      stimulus. METHODS: In 17 patients with functional dyspepsia and 10 healthy
      controls 20-channel antropyloroduodenal manometry was performed. During phase II
      of the migrating motor complex small volumes (5 ml) of saline, acid, lipids, and
      dextrose were administered intraduodenally. Motility parameters and sensation
      scores for nausea, fullness, and epigastric pain were compared before and after
      each infusion and among the two groups. RESULTS: Acid induced a duodenal motor
      response in both groups, but less pressure waves (p < 0.05) and antegrade
      propagated pressure waves (p < 0.05) were observed in patients than in controls.
      In both groups lipids induced a similar, prominent increase in duodenal pressure
      waves. Acid and lipids suppressed antral-propagated pressure waves in both
      groups. Dextrose induced a modest increase in duodenal-propagated pressure waves
      in patients (p < 0.05) but not in controls. Although all infusions induced a mild
      increase in nausea in patients, only acid induced a significant increase in
      nausea after 1 min (p < 0.01). None of the infusions affected the sensations of
      epigastric pain or fullness in patients, nor did any infusions induce sensations
      in controls. CONCLUSIONS: In functional dyspepsia alterations in sensor and motor
      responses to intraduodenal acid and nutrients are chemospecific, suggesting an
      abnormality at the level of visceral afferents or mucosal chemoreceptors in these
      patients.

PMID- 11569682
TI  - The importance of vacA, cagA, and iceA genotypes of Helicobacter pylori infection
      in peptic ulcer disease and gastroesophageal reflux disease.
AB  - OBJECTIVE: To study the relationship between the presence of H. pylori virulence
      factors and clinical outcome in H. pylori infected patients. METHODS: DNA was
      isolated from an antral biopsy sample and vacA, cagA, and iceA genotype were
      determined by PCR and a reverse hybridization technique in 183 patients with
      culture-proven H. pylori infection: 51 with peptic ulcer disease (PUD), 62 with
      gastroesophageal reflux disease (GERD), and 70 with a normal endoscopy (gastritis
      only; GO). RESULTS: Forty-four samples (24%) showed more than one allelic variant
      in the vacA s- or in-region and/or both iceA1 and iceA2 genotypes, indicating
      multiple strain infection. These were excluded from statistical analysis. vacA s1
      and cagA were significantly more common in PUD than in GERD and GO. Logistic
      regression analysis showed that GERD patients were more often infected with
      strains lacking both cagA and iceA than GO patients (OR = 0.36; CI = 0.15-0.89).
      Trend analysis showed that GERD patients were most often infected with less
      virulent strains (p < 0.002). CONCLUSION: Multiple strain infection is common. H.
      pylori strains possessing the vacA s1 genotype and/or cagA are associated with
      PUD. GERD patients, infected with H. pylori, mostly carry less virulent strains
      possessing neither cagA nor iceA1. Our findings support the hypothesis that
      virulent strains protect against the development of GERD.

PMID- 11569683
TI  - Long term survival after pancreatic resection for pancreatic adenocarcinoma.
AB  - OBJECTIVE: The aim of this study was to determine the long term survival of
      patients with pancreatic adenocarcinoma who underwent surgical resection and to
      assess the association of clinical, pathological, and treatment features with
      survival. METHODS: Between January, 1990, and December, 1998, 125 patients
      underwent a pancreaticoduodenal or partial pancreatic resection for pancreatic
      ductal adenocarcinoma at our institution. The records of these patients were
      reviewed for demographics, tumor characteristics including size, histological
      grade, margin status, lymph node status, surgical TNM staging, and postoperative
      adjuvant therapy. The primary outcome variable analyzed was survival. RESULTS: A
      total of 116 patients had complete follow-up and were included in the final
      analysis. The median survival after surgery was 16 months. The 1-, 3-, 5-, and 7
      yr survival rates for all 116 patients were 60%, 23%, 19%, and 11%, respectively.
      The 1-, 3-, 5-, and 7-yr survival rates for patients who received adjuvant
      therapy were 69%, 28%, 23%, and 18% compared with 20% and 0% in patients who did
      not receive adjuvant therapy (p < 0.0001). The 1-, 3-, 5-, and 7-yr survival
      rates for patients with negative lymph nodes were 73%, 38%, 26%, and 22% compared
      with survival rates of 52%, 14%, 14%, and 9% in patients with positive lymph
      nodes (p = 0.01). In multivariate analyses, adjuvant therapy was the only feature
      found to be strongly associated with survival (hazards ratio = 0.26, 95% CI =
      0.15-0.44). CONCLUSIONS: The overall 5- and 7-yr survival rates of 19% and 11% in
      our study further validate that surgical resection in patients with pancreatic
      adenocarcinoma can result in long term survival, particularly when performed in
      association with adjuvant chemoradiation.

PMID- 11569684
TI  - Endoscopic fluorescence spectroscopy in the upper GI tract for the detection of
      GI cancer: initial experience.
AB  - OBJECTIVE: The aim of this study was to investigate autofluorescence spectroscopy
      using violet-blue excitation light for the in vivo diagnosis of GI cancer during
      routine endoscopy. METHODS: Fluorescence spectra were obtained from normal mucosa
      and cancerous lesions of the esophagus and stomach. The spectroscopic system used
      comprised a special light source capable of delivering either white or violet
      blue light to induce autofluorescence of tissue via the endoscope. Endogenous
      fluorescence spectra emitted by the tissue were recorded with a fiberoptic probe
      and analyzed with a spectrographic detector system consisting of a polychromator
      with a photodiode array and an optical multichannel analyzer. The data of each
      spectrum were sampled within the range of 450-700 nm and stored in a personal
      computer. RESULTS: Esophageal squamous cell cancer, adenocarcinoma of the
      esophagus, and adenocarcinoma of the stomach show specific differences in the
      emitted fluorescence spectra compared with normal mucosa. CONCLUSIONS: Light
      induced fluorescence spectroscopy might be a useful tool for the endoscopic in
      vivo detection of dysplasia and early carcinoma in the upper GI tract. Further
      trials are needed to test the validity of this new optical detection system.

PMID- 11569685
TI  - Associations of alcohol drinking and nutrient intake with chronic pancreatitis:
      findings from a case-control study in Japan.
AB  - OBJECTIVE: The aim of this study was to examine the association of alcohol
      drinking and nutrient intake with chronic pancreatitis in a hospital-based case
      control study. METHODS: From July, 1997, to December, 1998, 91 male patients, who
      were newly diagnosed as having chronic pancreatitis, were recruited as cases, and
      175 controls were individually matched to each case for gender, age (+/-5 yr),
      hospital, and time of the first visit to a hospital (+/-1 yr). Information on
      demographic characteristics, smoking and drinking, and dietary habits were
      collected by a self-administered questionnaire. The strength of associations was
      examined by odds ratios (ORs) and 95% CIs calculated from conditional logistic
      regression models. RESULTS: Our study showed that the more the daily amount of
      alcohol drinking, the larger the OR. Men who consumed > or =100 g ethanol/day
      were at an approximately 11-fold increased risk as compared with nondrinkers.
      Long-term alcohol consumption (>35 yr) was associated with the increased risk (OR
      = 4.0). Risk of chronic pancreatitis remarkably increased with increasing
      cumulative alcohol consumption (trend p = 0.0001). Intakes of saturated fatty
      acid and vitamin E were negatively associated with the risk (trend p = 0.05 for
      saturated fatty acid and 0.03 for vitamin E). CONCLUSION: Our study clearly
      demonstrated that prolonged heavy alcohol consumption was an important and
      independent risk factor, and suggested a role of lower nutrient intakes in the
      development of chronic pancreatitis.

PMID- 11569686
TI  - Magnifying colonoscopy in differentiating neoplastic from nonneoplastic
      colorectal lesions.
AB  - OBJECTIVE: Because the medical management of persons with adenomatous colorectal
      polyps differs from that of those with hyperplastic polyps, accuracy of diagnosis
      is essential. This study reports our experience using a magnifying colonoscope
      combined with indigocarmine dye to diagnose colorectal polyps, emphasizing its
      ability to differentiate neoplastic from nonneoplastic lesions. METHODS: The
      materials consisted of 175 polyps. A 0.2% indigocarmine solution was sprayed, and
      the colonoscope zoom apparatus performed a magnified observation after an
      ordinary colonoscopy identified the lesions. The pit patterns were classified
      into six categories: I, II, III(L), IIIs, IV, and V according to Kudo's modified
      classification. RESULTS: The percentages of neoplastic changes in the lesions
      with pit pattern I, II, III(L), IIIs, IV, and V were 0, 12.2, 69.7, 80, 84.4, and
      100%, respectively. The diagnostic sensitivity of neoplastic lesions was 93.8%
      and specificity was 64.6% when types I and II represented the pit pattern of
      nonneoplastic lesions and types III(L), IIIs, IV, and V represented neoplastic
      lesions. The overall diagnostic accuracy in differentiating neoplastic from
      nonneoplastic lesions was 80.1%. The diagnostic accuracy is not influenced by the
      size and shape of the lesions. The six neoplastic lesions that were misjudged to
      be nonneoplastic were histologically adenoma with only mild atypia. CONCLUSIONS:
      The pit pattern analysis of colorectal lesions by magnifying colonoscopy is a
      useful and objective tool for differentiating neoplastic from nonneoplastic
      lesions of the large bowel. In its current state of development, however, this
      technique is not a substitute for histology.

PMID- 11569687
TI  - Optical coherence tomography of the esophagus and proximal stomach in health and
      disease.
AB  - OBJECTIVE: Surveillance of Barrett's esophagus is problematic, as high-grade
      dysplasia cannot be recognized endoscopically. Endoscopic ultrasound lacks the
      resolution to detect high-grade dysplasia. Optical coherence tomography (OCT)
      employs infrared light reflectance to provide in vivo tissue images at resolution
      far superior to endoscopic ultrasound, nearly at the level of histology. We have
      developed a catheter-based system well suited for study of the GI tract. The
      purpose of this study was to test this catheter-based OCT system and characterize
      the OCT appearance of normal squamous mucosa, gastric cardia, Barrett's
      esophagus, and carcinoma. METHODS: The OCT catheter was passed through the
      operating channel of the endoscope and placed in contact with the esophageal
      mucosa. Image acquisition occurred in approximately 3 s. OCT images were
      correlated with biopsy and/or resection specimens. RESULTS: OCT was used to
      construct 477 images of the esophagus and stomach in 69 patients. There were
      unique, distinct OCT appearances of squamous mucosa, gastric cardia, Barrett's
      esophagus, and carcinoma. Further, these OCT images were accurately recognized by
      observers unaware of their site of origin. CONCLUSIONS: OCT provides a highly
      detailed view of the GI wall, with clear delineation of a multiple layered
      structure. It is able to distinguish squamous mucosa, gastric cardia, Barrett's
      esophagus, and cancer. This technique holds great potential as an adjunct to the
      surveillance of patients with Barrett's esophagus, ulcerative pancolitis, and
      other premalignant conditions.

PMID- 11569688
TI  - Evaluation of a rapid urine amylase test using post-ERCP hyperamylasemia as a
      model.
AB  - OBJECTIVE: The initial diagnosis of acute pancreatitis is often based on clinical
      criteria together with elevations of serum amylase and lipase. A reliable bedside
      urine test could facilitate the early diagnosis of pancreatitis. We evaluated a
      rapid urine amylase test (Rapignost) by using post-ERCP hyperamylasemia as a
      human model of acute development of hyperamylasemia suggestive of pancreatitis.
      METHODS: Seventy-five patients undergoing ERCP were prospectively evaluated.
      Patients with renal insufficiency, hyperlipidemia, or hyperglycemia were
      excluded. Before ERCP, patients had serum amylase and lipase measured, and urine
      amylase tested with the Rapignost test strip. At 4 and 16-24 h post-ERCP, a serum
      and urine (test strip) amylase were measured again; the adequacy of urine
      collection was verified by measuring a 2-h creatinine clearance. Patients were
      clinically assessed for the development of clinical pancreatitis. The concordance
      of the strip result with post-ERCP hyperamylasemia was assessed. RESULTS: The
      sensitivity of the test strip for the detection of hyperamylasemia was greatest
      at 16-24 h post-ERCP (78%). Specificity was uniformally high (100% specificity at
      16-24 h post-procedure). The test strip was positive in all cases of clinical
      pancreatitis. Of three cases of clinically evident ERCP-induced pancreatitis,
      only one was urine test strip positive by 4 h post-procedure. CONCLUSIONS: Using
      post-ERCP hyperamylasemia as a model, the Rapignost rapid urine amylase test
      strip was only marginally sensitive but highly specific for hyperamylasemia. The
      urine test strip was positive in all cases of clinical pancreatitis and may be a
      useful bedside test for the diagnosis of acute pancreatitis.

PMID- 11569689
TI  - Patient satisfaction after MRCP and ERCP.
AB  - OBJECTIVE: Magnetic resonance cholangiopancreatography (MRCP) is an accurate
      diagnostic test for detecting abnormalities of the pancreaticobiliary system.
      Because it is noninvasive, MRCP appears to be more tolerable than ERCP, although
      this has not been studied. The purpose of this study is to compare patient
      satisfaction after MRCP and ERCP performed sequentially. METHODS: We
      prospectively recruited 34 patients undergoing ERCP, for whom an MRCP was able to
      be performed before ERCP. Patient satisfaction was assessed by validated
      questionnaires using seven-point Likhert scales (individual ratings and direct
      comparisons). The following dimensions were explored: anxiety, pain, discomfort,
      tolerability (relative to expectations), willingness to repeat the procedure, and
      overall preference. Chi2 and Student's t tests (paired and unpaired) were
      performed, and 95% CIs were provided. RESULTS: Two patients (5.9%) were unable to
      undergo MRCP because of claustrophobia. The remaining 32 completed both tests
      (94% same day) and all questionnaires. Average age was 56+/-18 yr, and 66% were
      women. In 23 patients, some degree of biliary obstruction was suspected; nine
      patients had pancreatitis. Patients reported a lower degree of pain (p < 0.001)
      and discomfort (p = 0.047) with MRCP, but MRCP was more difficult than they
      expected (p = 0.0 12). Patients were marginally more willing to repeat MRCP (ns,
      p = 0.09). On direct comparisons, patients were more satisfied with MRCP
      regarding anxiety (p = 0.04) and pain (p = 0.001). Patients displayed a higher
      overall preference for MRCP compared with ERCP (p = 0.01); however, only 59%
      clearly preferred MRCP over ERCP. The most common problem with MRCP was
      claustrophobia or noise (n = 15), and the differences were more striking in the
      subgroup without this problem. The subgroup undergoing purely diagnostic ERCPs
      showed clear preferences for MRCP. CONCLUSIONS: In many respects, MRCP is well
      tolerated, and certain subgroups, especially those undergoing diagnostic ERCPs,
      prefer MRCP over ERCP. As an endoscopist, one needs to be aware of the
      limitations of MRCP and relay these to the patient, as it seems that patients
      find MRCP more difficult than anticipated, and a significant number still prefer
      ERCP over MRCP. Patient satisfaction may be further improved by reducing noise
      and claustrophobia with selective premedication, earplugs, and the use of the new
      quieter fenestrated magnetic resonance imaging scanners.

PMID- 11569690
TI  - A cost analysis of endoscopic ultrasound in the evaluation of pancreatic head
      adenocarcinoma.
AB  - OBJECTIVE: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy
      of nonperitumoral (NPT) lymph nodes (LN) can be helpful in preoperative staging
      of pancreatic head adenocarcinoma. The economic impact of this staging strategy
      has not yet been described. The aim of this study was to apply a decision
      analysis model to compare the costs of three approaches to the management of
      nonmetastatic pancreatic head adenocarcinoma: EUS FNA versus CT-guided FNA versus
      surgery. A cost minimization approach was employed, as viewed from the
      perspective of the payer. METHODS: A decision analysis model was designed using
      DATA Version 3.5, taking the entry criteria as "resectable" pancreatic head
      adenocarcinoma as determined by helical CT. Detection of metastatic NPT LN on FNA
      signified unresectability and obviated the need for surgery. Baseline
      probabilities were varied through plausible ranges using sensitivity analysis.
      Cost inputs were based on Medicare professional plus facility fees. The endpoint
      was cost of management per patient. RESULTS: EUS FNA was the least costly
      strategy ($15,938) compared with CT FNA ($16,378) and surgery ($18,723).
      Sensitivity analysis revealed that EUS FNA remained the least costly option
      provided the frequency of NPT LN involvement was >4%; below this value, surgery
      became the least costly. CONCLUSIONS: EUS FNA is the least costly staging
      strategy in the workup of patients with nonmetastatic pancreatic head
      adenocarcinoma primarily because of confirmation of NPT LN involvement avoiding
      unnecessary surgery. These results support performing EUS in patients whose
      tumors are thought to be resectable on helical CT to enhance NPT LN assessment.

PMID- 11569691
TI  - Mutations of the cystic fibrosis gene in patients with chronic pancreatitis.
AB  - OBJECTIVE: Several studies have reported an increased frequency of cystic
      fibrosis gene mutations in idiopathic but not in alcoholic chronic pancreatitis.
      The impact of cystic fibrosis gene mutations on the long-term course of chronic
      pancreatitis has not been analyzed. The aim of our study was to determine the
      frequency of cystic fibrosis gene mutations in patients with chronic pancreatitis
      with long-term follow-up and to see whether patients with mutations have a
      clinically different natural course compared to those without mutations. METHODS:
      Eighty two patients with chronic pancreatitis and 11 patients with recurrent
      acute pancreatitis of our well defined pancreatitis cohort were screened for the
      31 most common cystic fibrosis gene mutations. The impact of cystic fibrosis gene
      mutations on the long-term course of chronic pancreatitis was assessed. RESULTS:
      A cystic fibrosis gene mutation was detected in five of 49 patients with
      alcoholic chronic pancreatitis (10.2%; 2.3 times the expected frequency) and in
      three of 14 patients with idiopathic-juvenile chronic pancreatitis (21.4%; 4.8
      times the expected frequency). No mutations were found in the remaining patients
      with chronic pancreatitis of rare causes, hereditary pancreatitis, and recurrent
      acute pancreatitis. The frequency of pancreatic calcifications was significantly
      higher in patients with alcoholic chronic pancreatitis without mutations. This
      result was not confirmed in patients with idiopathic-juvenile chronic
      pancreatitis. The duration of pain and the frequency of exocrine and endocrine
      insufficiency was comparable in both subgroups irrespective of the mutation
      status. CONCLUSION: Our data indicate a significantly increased frequency of
      cystic fibrosis gene mutations both in patients with alcoholic and idiopathic
      juvenile chronic pancreatitis. The natural course was similar in patients with
      mutations compared to those without mutations.

PMID- 11569692
TI  - Alosetron controls bowel urgency and provides global symptom improvement in women
      with diarrhea-predominant irritable bowel syndrome.
AB  - OBJECTIVES: Bowel urgency is one of the most bothersome symptoms for
      nonconstipated IBS patients. The efficacy of alosetron in control of bowel
      urgency and Global Improvement of IBS symptoms were evaluated in a multicenter
      double-blind, randomized, placebo-controlled study. METHODS: Female IBS patients
      with lack of satisfactory control of bowel urgency were randomized 2:1 to
      alosetron 1 mg twice daily or placebo treatment groups. The primary endpoint was
      the proportion of days with satisfactory control of bowel urgency during the 12
      wk treatment period and 2-wk follow-up period. Secondary endpoints included IBS
      Global Improvement (responder defined as patient-reported moderate or substantial
      improvement in IBS symptoms) and improvements in bowel function (stool frequency,
      consistency, and sensation of incomplete evacuation). RESULTS: A total of 801
      women were randomized to the alosetron (n = 532) or placebo groups (n = 269).
      Physicians classified 98% of patients with diarrhea-predominant IBS. Patients
      treated with alosetron had a significantly greater proportion of days with
      satisfactory control of urgency compared to placebo for the treatment period (73%
      vs 57%, p < 0.001). A significantly greater number of patients treated with
      alosetron were IBS Global Improvement responders compared to placebo at week 12
      (76% vs 44%, p < 0.001). IBS Global Improvement responders had more days with
      satisfactory control of urgency at week 12 (88% vs 48%) as well as firmer stools,
      fewer stools/day, and fewer days with incomplete evacuation compared with
      nonresponders. Alosetron-treated patients showed improvements in bowel functions
      compared to placebo-treated patients. Constipation was the most commonly reported
      adverse event.

PMID- 11569693
TI  - Gender-related differences in slowing colonic transit by a 5-HT3 antagonist in
      subjects with diarrhea-predominant irritable bowel syndrome.
AB  - OBJECTIVE: To evaluate the influence of gender on the effect of a 5-HT3
      antagonist, alosetron, 1 mg b.i.d., on GI and colonic transit in D-IBS. METHODS:
      Thirty patients (15 male, 15 female) with D-IBS received 1 mg b.i.d. alosetron
      for 6 wk. Transit was measured by scintigraphy at baseline and at the end of
      treatment. RESULTS: Alosetron, 1 mg b.i.d., significantly retarded small bowel
      and, proximal and overall colonic transit in the 30 patients with D-IBS. The
      effect of alosetron on the primary endpoint, colonic geometric center at 24 h,
      was significantly greater in females than in males (p < 0.05). However, two
      females showed no slowing of colonic transit on treatment. Among male patients,
      two of 15 had a slowing of colonic transit at 24 h that was greater than the mean
      change in female patients, suggesting responsiveness to alosetron among a
      subgroup of males. CONCLUSION: A 5-HT3 antagonist, alosetron, significantly
      retards small intestinal and colonic transit in diarrhea-predominant IBS
      patients, with significantly greater female to male responsiveness. Gender partly
      contributes to differences in the serotonergic control of intestinal and colonic
      transit in patients with D-IBS.

PMID- 11569694
TI  - Hyperhomocysteinemia and prevalence of polymorphisms of homocysteine metabolism
      related enzymes in patients with inflammatory bowel disease.
AB  - OBJECTIVES: Patients with inflammatory bowel disease (IBD) have an increased risk
      of thrombotic complications. Moreover, a hypercoagulable state has been
      hypothesized as a contributing factor in the pathogenesis of IBD. Recently, a
      growing amount of interest has focused on mild-to-moderate hyperhomocysteinemia
      as a risk factor for thromboembolic disease. We aimed to evaluate the prevalence
      of hyperhomocysteinemia in patients with IBD and to investigate the contribution
      of genetic defects in the enzymes involved in homocysteine (Hcy) metabolism and
      vitamin status in determining increased levels of plasma total Hcy (tHcy).
      METHODS: The concentrations of tHcy, folate, and vitamin B12 as well as the
      prevalence of methylenetetrahydrofolate reductase (MTHFR) 677C to T mutation and
      the 68-bp insertion at exon 8 of cystathionine beta-synthase (CBS) were measured
      in patients with IBD and healthy controls. RESULTS: In all, 17 out of 64 IBD
      patients (26.5%) and four out of 121 (3.3%) controls had hyperhomocysteinemia
      with a statistically significant difference (p < 0.0001). No significant
      difference was found between IBD patients and controls with regard to the
      prevalence of homozygotes for the C677T variant (TT) of MTHFR or the prevalence
      of heterozygotes for the CBS-gene mutation (IN). Among the IBD patients the only
      independent factor significantly associated with hyperhomocysteinemia was folate
      deficiency (p = 0.0002), regardless of the MTHFR or the CBS genotype.
      CONCLUSIONS: IBD patients have a higher prevalence of hyperhomocysteinemia than
      do healthy controls. Folate deficiency is the only independent risk factor in
      developing hyperhomocysteinemia.

PMID- 11569695
TI  - Biological variability of fecal calprotectin in patients referred for colonoscopy
      without colonic inflammation or neoplasm.
AB  - OBJECTIVE: Fecal calprotectin concentration in stool has recently been proposed
      as a marker of colonic neoplasm and inflammation, but the intraindividual day-to
      day variability has so far received little attention. The present study was
      undertaken to determine the biological variability of fecal calprotectin in
      patients referred for colonoscopy. METHODS: A prospective design was applied. In
      each of 14 consecutive patients submitted for colonoscopy, eight stool samples
      were collected before the endoscopy. A detailed questionnaire was used.
      Calprotectin was measured by quantitative enzyme-linked immunoassay, and standard
      deviation for the within-patient variability was estimated from one-way analysis
      of variance. RESULTS: In absence of colonic neoplasm and inflammation, two
      populations of patients emerged: one (36%) with remarkably low and stable fecal
      calprotectin values all within the recommended cut-off of 50 microg/g, and one
      (64%) with labile values also beyond this limit. In this latter group. fecal
      calprotectin was 70 microg/g (mean) (single tests ranged from 9 to 461), and SD
      within patients was 52 microg/g, showing considerable day-to-day variation.
      History, concurrent diseases, or findings at colonoscopy could not explain labile
      values. A similar pattern was observed for spot variation in one stool sample
      from healthy volunteers, suggesting that factors other than disease contribute to
      the significant intraindividual biological variation of fecal calprotectin.
      CONCLUSIONS: Day-to-day variation of fecal calprotectin is considerable in
      patients without colonic inflammation or neoplasm, for whom the pattern of
      stabile low fecal calprotectin may seem to be a valid negative predictor. The
      origin and pattern of fecal calprotectin excretion deserve further attention.

PMID- 11569696
TI  - Failure of single-toxin assays to detect clostridium difficile infection in
      pediatric inflammatory bowel disease.
AB  - OBJECTIVES: The aims of this retrospective study were 1) to determine the ability
      of single-toxin assays for Clostridium difficile to detect infection among
      pediatric patients with inflammatory bowel disease (IBD) and 2) to determine the
      toxin assays routinely used by pediatric tertiary care hospitals in the United
      States. METHODS: Stool specimens from patients with IBD (submitted from January,
      1996, to August, 1999) were evaluated for the presence of C. difficile toxin A
      and toxin B. Toxin profile (toxin A alone, toxin B alone, toxin A and B together)
      was compared in positive specimens. A phone interview was conducted with
      representatives from laboratories in 22 pediatric hospitals to investigate which
      toxin assays were routinely used. RESULTS: A total of 697 specimens were
      submitted from 284 IBD patients. In all, 81 IBD patients (28.5%) had at least one
      documented infection. Toxin A assay failed to identify 41.5% of C. difficile
      infections. Toxin B assay failed to detect 34.9% of C. difficile infections.
      Toxin profile changed in 55% of patients with multiple infections. Of the
      hospitals surveyed, 59% did not test for both toxins. CONCLUSIONS: Single-toxin
      assays for C. difficile fail to detect a significant percentage of infections.
      The toxins identified during one infection are not predictive of the toxins
      identified in subsequent infections. Despite this, many pediatric hospitals do
      not routinely use both toxin assays to diagnose C. difficile infection. When
      infection is suspected, assays for C. difficile toxin A and toxin B should be
      requested.

PMID- 11569697
TI  - Expression of cytokines, inducible nitric oxide synthase, and matrix
      metalloproteinases in pouchitis: effects of probiotic treatment.
AB  - OBJECTIVE: The efficacy of probiotic organisms in the treatment of pouchitis has
      been reported. In the present study, we evaluated the tissue levels of pro- and
      anti-inflammatory cytokines, nitric oxide synthase, and matrix metalloproteinases
      in control and inflamed pouches before and after antibiotic and probiotic
      treatment of patients with acute pouchitis. METHODS: Pouch biopsy samples were
      obtained from seven patients with pouchitis before and after antibiotic and
      probiotic treatment. Tissue samples from five patients with normal pouches were
      used as controls. Cytokines were determined by ELISA, matrix metalloproteinase
      activity was evaluated by zymograms, and nitric oxide synthase activity was
      determined by measuring arginine to citrulline conversion. RESULTS: Tissue levels
      of tumor necrosis factor a increased (p < 0.01) in pouchitis relative to
      uninflamed pouches and reduced after antibiotic and probiotic treatment. Also,
      interferon y and interleukin 1alpha (IL-1alpha) augmented in pouchitis, but their
      increase did not reach statistical significance. The latter, however, were lower
      (p < 0.05) after treatment with the antibiotics and probiotics. Tissue levels of
      IL-4 and IL-10 were unchanged in inflamed pouches and unaffected by antibiotic
      treatment. However, IL-10 increased (p < 0.05) after probiotic treatment.
      Moreover, inflamed pouches had higher levels of inducible nitric oxide synthase
      and gelatinase activities, which decreased after treatment. CONCLUSIONS: The
      ability of antibiotic and probiotic treatments to increase tissue levels of IL
      10, at a higher level than those observed in control pouches, and to decrease, to
      levels present in control pouches, proinflammatory cytokine, inducible nitric
      oxide synthase, and matrix metalloproteinase activity may suggest a mechanism of
      action to explain the efficacy of this therapeutic regime in pouchitis.

PMID- 11569698
TI  - Prevalence of celiac disease in Argentina: screening of an adult population in
      the La Plata area.
AB  - OBJECTIVES: Up to now, the epidemiological characteristic of celiac disease among
      adults in South America remains unknown. The present prospective screening was
      designed to determine the prevalence of celiac disease in adults from the general
      population in an urban area of Argentina. METHODS: Between January. 1998, and
      May, 2000, all couples attending a centralized laboratory for an obligatory
      prenuptial examination in the La Plata area were offered participation in a
      screening program for celiac disease. The study included 2000 subjects (996
      women; median age 29 yr, range 16-79 yr). All individuals completed a clinical
      questionnaire at the time that serum samples were obtained. A three-step
      screening protocol was used, as follows: 1) all samples were tested for
      antigliadin antibodies (AGAs) (type IgA and IgG); 2) samples that were IgA AGA
      positive were tested for antiendomysial antibody (EmA type IgA); samples that
      were positive for AGA-G but negative for IgA AGAs were tested for total IgA serum
      levels and EmA type IgG; and 3) subjects who were EmA-positive were referred for
      intestinal biopsy. RESULTS: At the end of the screening we detected 10 subjects
      who were EmA-A positive and two others who were IgA-deficient (both were EmA-G
      positive). Up to now, 11 of the 12 subjects (including nine EmA-positive and two
      IgA-deficient subjects) had endoscopic intestinal biopsies showing the
      characteristic celiac histology. The remaining EmA-positive individual was
      considered to be affected by celiac disease. The overall prevalence assessed was
      1:167 (6.0 x 1000 subjects; 95% CI = 3.1-10.5). Eight of the 12 (67%) subjects
      were female (1:124; 8.0 x 1000; 95% CI = 3.5-15.8) and four (33%) were male
      (1:251; 4.0 x 1000; 95% Cl = 1.1-10.2). Although eight new patients were
      considered to be asymptomatic, three presented with a subclinical course and one
      was classically symptomatic. Only one patient had been previously diagnosed with
      celiac disease. CONCLUSIONS: Our screening protocol showed a very high prevalence
      of celiac disease for an urban area of Argentina that is ethnically similar to
      90% of the general population of the country. The prevalence among women was
      double that for men, and the heterogeneous clinical picture of new patients
      showed predominance of asymptomatic cases.

PMID- 11569699
TI  - Serum angiotensin I-converting enzyme is reduced in Crohn's disease and
      ulcerative colitis irrespective of genotype.
AB  - OBJECTIVES: Crohn's disease (CD) is recognized to be a vascular endothelial
      associated disease. Angiotensin I-converting enzyme (ACE) exists mainly in
      endothelial cells. There are some reports on serum ACE levels in patients with
      CD, but the ACE level is still controversial. Recently, genetic control of serum
      ACE levels by ACE gene polymorphisms (classified as II, ID, and DD) has been
      suggested. Although we must consider such polymorphisms to elucidate ACE levels
      in patients with CD, there is no report about this. METHODS: We studied 341
      healthy controls (male/female = 178/162), 39 patients with CD (31/8), 43 patients
      with ulcerative colitis (UC) (22/21) and 19 patients with infectious
      enterocolitis (8/11). The polymorphism in intron 16 of the ACE gene was examined
      by PCR. Serum ACE levels were measured by the method of Kasahara. RESULTS: Serum
      ACE levels in patients with CD and UC were significantly lower than in healthy
      controls, irrespective of the genotype of ACE (genotype II: CD 7.0+/-2.5 [mean +/
      SD], UC 7.1+/-3.3, controls 11.8+/-2.9, genotype ID: CD 9.7+/-4.1, UC 11.4+/
      4.6, controls 15.2+/-3.6, genotype DD: CD 13.9+/-5.8, UC 10.7+/-3.6, controls
      19.3+/-3.9 IU/L, controls vs CD, UC; p < 0.01, 0.05). However, there was no
      significant difference in serum ACE levels between CD and UC. CONCLUSIONS:
      Considering ACE gene polymorphism, serum ACE levels in patients with inflammatory
      bowel disease are lower than in controls. Serum ACE levels reflect a part of the
      pathogenesis of inflammatory bowel disease.

PMID- 11569700
TI  - Betaine, a promising new agent for patients with nonalcoholic steatohepatitis:
      results of a pilot study.
AB  - OBJECTIVES: No effective therapy currently exists for patients with nonalcoholic
      steatohepatitis (NASH). Betaine, a naturally occurring metabolite of choline, has
      been shown to raise S-adenosylmethionine (SAM) levels that may in turn play a
      role in decreasing hepatic steatosis. Our aim was to determine the safety and
      effects of betaine on liver biochemistries and histological markers of disease
      activity in patients with NASH. METHODS: Ten adult patients with NASH were
      enrolled. Patients received betaine anhydrous for oral solution (Cystadane) in
      two divided doses daily for 12 months. Seven out of 10 patients completed 1 yr of
      treatment with betaine. RESULTS: A significant improvement in serum levels of
      aspartate aminotransferase (p = 0.02) and ALAT (p = 0.007) occurred during
      treatment. Aminotransferases normalized in three of seven patients, decreased by
      >50% in three of seven patients, and remained unchanged in one patient when
      compared to baseline values. A marked improvement in serum levels of
      aminotransferases (ALT -39%; AST -38%) also occurred during treatment in those
      patients who did not complete 1 yr of treatment. Similarly, a marked improvement
      in the degree of steatosis, necroinflammatory grade, and stage of fibrosis was
      noted at 1 yr of treatment with betaine. Transitory GI adverse events that did
      not require any dose reduction or discontinuation of betaine occurred in four
      patients. CONCLUSIONS: Betaine is a safe and well tolerated drug that leads to a
      significant biochemical and histological improvement in patients with NASH. This
      novel agent deserves further evaluation in a randomized, placebo-controlled
      trial.

PMID- 11569701
TI  - Subclinical hepatic encephalopathy predicts the development of overt hepatic
      encephalopathy.
AB  - OBJECTIVES: In patients with compensated liver cirrhosis the clinical
      repercussions of detecting subclinical hepatic encephalopathy (SHE) are unclear.
      We present a long-term follow-up study in cirrhotic patients to examine the
      relationship between SHE and subsequent episodes of overt hepatic encephalopathy.
      METHODS: A total of 63 cirrhotic patients were studied by Number Connection Test
      and auditory evoked potentials. We determined glutamine, ammonia, zinc,
      glutamate, urea, and ratio of branched chain amino acids to aromatic amino acids,
      and Child-Pugh classification. RESULTS: Of 63 patients, 34 (53%) exhibited SHE.
      Nineteen out of 63 (30%) developed overt hepatic encephalopathy during follow-up.
      Hepatic encephalopathy in follow-up was related to alcoholic etiology, ammonia,
      glutamine, zinc, ratio of branched chain amino acids to aromatic amino acids,
      liver function, presence of esophageal varices, and detection of SHE (84% of
      patients who exhibited hepatic encephalopathy in follow-up showed SHE). In Cox
      regression, glutamine levels, SHE, esophageal varices, and Child-Pugh class were
      the independent variables related to hepatic encephalopathy in follow-up.
      CONCLUSIONS: SHE (defined on the basis of number connection test or auditory
      evoked potentials alteration) could predict a subsequent episode of overt hepatic
      encephalopathy. Lower glutamine levels, presence of esophageal varices, and liver
      dysfunction were also related to the development of overt hepatic encephalopathy.

PMID- 11569702
TI  - Dendroaspis natriuretic peptide in hepatic cirrhosis.
AB  - OBJECTIVES: Dendroaspis natriuretic peptide (DNP) is a novel peptide that is
      structurally similar to atrial, brain, and C-type natriuretic peptides. Many
      natriuretic peptides are increased in hepatic cirrhosis, but the role of DNP in
      cirrhosis is unknown at present. The aim of the study was to investigate plasma
      levels of dendroaspis natriuretic-like immunoreactivity in cirrhosis. METHODS: We
      measured plasma concentrations of DNP by radioimmunoassay methods in 12 cirrhotic
      patients without ascites and 44 cirrhotic patients with ascites, and compared
      these values with 20 age-matched healthy subjects. Renal function, plasma cGMP
      concentration, plasma renin activity, and plasma endothelin concentration were
      measured in each patient. RESULTS: Patients without ascites had circulating
      levels of DNP similar to those of healthy subjects. By contrast, patients with
      ascites had increased circulating DNP levels compared to both patients without
      ascites and healthy subjects. In addition, circulating levels of DNP increased in
      relation to the severity of cirrhosis. Significant positive correlations were
      also found between DNP levels, endothelin concentrations, and plasma renin
      activity. CONCLUSIONS: The results of this study indicate that plasma DNP is
      increased in cirrhotic patients with ascites.

PMID- 11569703
TI  - Patients' values for health states associated with hepatitis C and physicians'
      estimates of those values.
AB  - OBJECTIVES: Hepatitis C is the leading cause of chronic hepatitis in the United
      States. Little information is available regarding how persons with hepatitis C
      view health with their disease. We studied patients' perceptions about the value
      of hepatitis C health states and evaluated whether physicians understand their
      patients' perspectives about this disease. METHODS: A total of 50 consecutive
      persons with hepatitis C were surveyed when they presented as new patients to a
      hepatology practice. Subjects provided utility assessments (preference values)
      for five hepatitis C health states and for treatment side effects. They also
      stated their threshold for accepting antiviral therapy. Five hepatologists used
      the same scales to estimate their patients' responses. RESULTS: On average,
      patients believed that hepatitis C without symptoms was associated with an 11%
      reduction in preference value from that of life without infection, and the most
      serious condition (severe symptoms, cirrhosis) was believed to carry a 73%
      decrement. Patients judged the side effects of antiviral therapy quite
      unfavorably, and their median stated threshold for accepting treatment was a cure
      rate of 80%. Physicians' estimates were not significantly associated with
      patients' preference values for hepatitis C health states, treatment side
      effects, or with patients' thresholds for accepting treatment. In multivariate
      analysis, patients' stated thresholds for taking treatment were significantly
      associated with their decisions regarding therapy (beta = -2.72+/-1.21, p =
      0.025). CONCLUSIONS: There was little agreement between patients' preference
      values about hepatitis C and their physicians' estimates of those values. Utility
      analysis could facilitate shared decision making about hepatitis C.

PMID- 11569704
TI  - Comorbid illness is an important determinant of health-related quality of life in
      patients with chronic hepatitis C.
AB  - OBJECTIVES: Chronic hepatitis C (CHC) patients selected for entry into treatment
      trials have been reported to have impaired health-related quality of life
      (HRQOL). However, these trials have an inherent selection bias, and HRQOL in CHC
      patients may have been underestimated because of the exclusion of patients with
      comorbid illness. The aim of this study was to assess HRQOL in an unselected
      group of CHC patients and to identify factors associated with impairment in
      HRQOL. METHODS: A total of 220 consecutive eligible CHC patients were enrolled
      from a hepatology clinic. HRQOL was assessed by the short form 36 (SF-36) and
      comorbid illnesses were assessed by an interview. RESULTS: CHC patients had
      significantly lower SF-36 scores in all subscales and in the summary scales when
      compared to those of the healthy general population in the United States (p <
      0.001). Compared to CHC patients entering treatment trials, our patients had
      lower SF-36 scores on five subscales (p < 0.001). The presence of comorbid
      illness was the most important predictor of HRQOL in CHC patients. However, CHC
      alone resulted in significantly lower SF-36 scores in all subscales and summary
      scales (p < or = 0.003) compared to those of the healthy U.S. population. There
      was no correlation between SF-36 scores and history of i.v. drug use or
      dependence. alcohol dependence. and serum aminotransferase levels. CONCLUSIONS:
      We conclude that unselected CHC patients presenting for medical evaluation have a
      reduced HRQOL, which is lower than that reported for CHC patients entering
      treatment trials. CHC alone is associated with significant impairment in HRQOL,
      but the presence of comorbid illness leads to further diminution in HRQOL.

PMID- 11569705
TI  - Fat-soluble vitamin levels in patients with primary biliary cirrhosis.
AB  - OBJECTIVE: To determine the occurrence of fat-soluble vitamin deficiencies and to
      identify clinical factors that may predict vitamin deficiency in patients with
      primary biliary cirrhosis (PBC). METHODS: Review of our data from a randomized,
      placebo-controlled trial that evaluated the efficacy of UDCA in 180 patients with
      PBC. We use the first available measurements of vitamin levels in each study
      participant. Vitamin levels for A, D, and E were measured in serum. The
      prothrombin time (PT) was used as a surrogate marker for vitamin K. RESULTS: The
      proportion of patients with fat-soluble vitamin deficiencies in the treatment and
      placebo groups was similar and the data sets were combined. The proportion with
      vitamin A, D, E or K deficiency was 33.5%, 13.2%, 1.9%, and 7.8%, respectively.
      In multivariate analysis, the Mayo risk score, advanced histological stage, and
      total cholesterol were independently associated with vitamin A deficiency whereas
      serum albumin levels was independently associated with vitamin D deficiency. No
      factors were associated with vitamin E or K deficiency in multivariate analysis
      owing to the few vitamin E and K deficient patients. Factors predictive of
      vitamin K deficiency by univariate analysis included Mayo risk score, advanced
      histological stage, HDL, total bilirubin, AST, and albumin. The cut-off value of
      the Mayo risk score with the highest sensitivity and specificity for vitamin A
      deficiency was 5.0. CONCLUSION: Other than deficiency of vitamin A, deficiency of
      fat-soluble vitamins occurs uncommonly in patients with PBC. A Mayo risk score >
      or = 5 helps in selecting patients with PBC for surveillance for vitamin A
      deficiency.

PMID- 11569706
TI  - Viral load in HCV RNA-positive pregnant women.
AB  - OBJECTIVES: The risk of hepatitis C virus (HCV) infection in the newborn is
      estimated to be around 5%, but becomes very high in the case of coinfection with
      HIV. One of the main factors associated with the vertical transmission of HCV is
      the viral load. Our objective was to investigate the behavior of HCV viral load
      during pregnancy in relation to HIV coinfection, liver enzymes, and vertical
      transmission. METHODS: Three thousand seven hundred forty-eight women seen
      consecutively in their first trimester of pregnancy were screened for HCV
      infection. Sixty-five were found to be anti-HCV+/HCV RNA+ and were followed up
      with clinical and serological assessment (i.e., transaminases and quantitative
      polymerase chain reaction [PCR] for viral load) in their second and third
      trimesters and 6 months after delivery. All were anti-HIV and hepatitis B surface
      antigen negative. HCV RNA was 12.0+/-19.9 x 10(6) copies/ml in the first
      trimester and 10.9+/-13.3 x 10(6) in the second, but increased to 19.5+/-25.1 x
      10(6) in the third trimester. Six months after delivery the viral load returned
      to the baseline levels; the changes in viral load did not reach any statistical
      significance, however. Transaminases tended toward a reduction from the baseline
      during the second and third trimesters, and then an increase in both AST and ALT
      was recorded 6 months after delivery. However, when the group whose AST/ALT were
      found abnormal at the first test was considered, no significant changes were
      recorded during the follow-up. The overall rate of vertical transmission was 4.6
      CONCLUSIONS: With HCV+ mothers monitoring transaminases during pregnancy is
      unnecessary, and testing liver enzymes at the beginning of pregnancy is
      sufficient. Qualitative PCR should be done once during the pregnancy, but any
      staging of the liver disease should be taken after delivery. Quantitative PCR
      testing is expensive and pointless. Any decision for elective cesarean section in
      HCV RNA+ mothers should be confirmed by other studies.

PMID- 11569707
TI  - Colorectal cancer in Russian-speaking Jewish emigres: community-based screening.
AB  - OBJECTIVES: Colorectal cancer (CRC) screening by fecal occult blood testing and
      flexible sigmoidoscopy is recommended by many authorities for those older than
      age 50. Ashkenazi Jews have been shown to have a higher level of CRC and polyps
      than the general population. A subset of Ashkenazi Jews, Russian-speaking Jewish
      immigrants to the United States (RJIs), have not been studied extensively for CRC
      and may have additional risk factors not found in other Ashkenazi populations.
      METHODS: A retrospective chart review was undertaken of fecal occult blood tests,
      endoscopy reports, and pathology reports of 132 RJIs and 124 non-RJI controls
      over age 50 between 1987 and 1999 at the Jewish Hospital of Cincinnati Medical
      Outpatient Clinic. RESULTS: Mean ages at the time of diagnosis or flexible
      sigmoidoscopy were 68 yr for RJIs and 66 yr for the non-RJI patients. Of the RJI
      patients, 38.7% had positive findings: 37 (28.0%) with lesions < 2 cm, five
      (3.8%) with lesions > 2 cm, and nine (6.8%) with CRC. Of the non-RJI control
      group patients, 16.9% had positive findings: 16 (12.9%) with lesions < 2 cm,
      three (2.4%) with lesions > 2 cm, and two (1.6%) with CRC. Age- and sex-matched
      statistical analysis revealed significantly greater CRC and significantly more
      polyps > 2 cm for the RJI patients (p < 0.003). This is higher than in other
      studies of Ashkenazis, which show a 2.3% incidence, and in statistics from the
      National Cancer Institute, which reveal a national CRC incidence rate for those
      over age 65 to be 0.30%. CONCLUSIONS: RJIs in our study have polyps > 2 cm and
      CRC at a rate of 10.6%, as compared with 4.0% for in-clinic controls and a
      national average of 0.30% for patients over age 65. This suggests a need for more
      aggressive screening of this patient population for CRC.

PMID- 11569708
TI  - Recurrence and malignancy rates in a benign colorectal neoplasm patient cohort:
      results of a 5-year analysis in a managed care environment.
AB  - OBJECTIVE: To estimate the apparent recurrence rates of benign neoplasms and the
      development of malignant colorectal neoplasms over a 5-yr period in a high risk
      managed care population. METHODS: Using the CPT and ICD-9 CM codes, a cohort of
      subjects with benign neoplasms were identified with a colonoscopy in 1992 from a
      longitudinal claims database (MarketScan). Three groups of subjects (benign
      neoplasms with polypectomy, benign neoplasms without polypectomy, and no
      neoplasms) were evaluated. Five-year recurrence rates of benign or new malignant
      colorectal neoplasms were determined for the baseline benign neoplasms with
      polypectomy and no neoplasm groups. For the benign neoplasm without polypectomy,
      only rates for malignancy were evaluated. RESULTS: Of 16,293 subjects at
      baseline, 39.50% were diagnosed with benign and 5.50% with malignant neoplasms.
      The 5-yr cumulative incidence of benign neoplasms in subjects without an index
      neoplasm (n = 8,967) was 7.92% compared to the recurrence of 40.93% in subjects
      with a benign neoplasm and polypectomy (n = 4,046) at baseline (p < 0.001). The 5
      yr cumulative incidence rates of malignant colorectal neoplasms in the no
      neoplasm (n = 8,967) and benign neoplasm groups (n = 6,438) were 1.81% and 2.55%,
      respectively (p < 0.005). A lower 5-yr malignancy rate was observed in benign
      neoplasm group with polypectomy (2.17%) compared to the benign neoplasm group
      without polypectomy (3.18%) (p < 0.05). CONCLUSION: The high recurrence rate of
      benign colorectal neoplasms and a higher incidence of colorectal cancer in
      subjects at high risk (history of benign colorectal neoplasm) highlight a
      healthcare opportunity for surveillance and/or interventions to reduce the
      morbidity associated with colorectal neoplasms.

PMID- 11569709
TI  - Rectal dilators.

PMID- 11569710
TI  - Immunoproliferative small intestinal disease: prolonged 30-year course without
      development of lymphoma.
AB  - Immunoproliferative small intestinal disease (IPSID) is mostly found in young
      adults of low socioeconomic class in developing countries. This condition is
      characterized by a dense lymphoplasmacytic infiltrate beneath the epithelium in
      the duodenal and proximal jejunal mucosa and in the mesenteric lymph nodes. In
      two thirds of cases, the involved lymphocytes elaborate an anomalous alpha-heavy
      chain protein. The etiology of this disease is unclear, although various
      parasitic, genetic, and toxic mechanisms have been proposed. Half of all IPSID
      patients will be found at diagnosis to have a concurrent intestinal B-cell
      lymphoma, and most of the remaining patients develop frank lymphoma within a few
      years. Although most reports of IPSID are from developing nations or indigent
      immigrant populations within Western countries, four cases of an IPSID-like
      condition have been documented in white women. Furthermore, although many IPSID
      patients progress to high grade indeterminate-type lymphoma within a few years of
      initial presentation, there have been occasional reports of long term survival
      without lymphomatous conversion. Here, we present an atypical case of IPSID--a
      California native who, though of Mexican heritage, had resided in the United
      States his entire life and did not belong to an indigent population. This patient
      had biopsy-proven IPSID that progressed over 30 yr but never exhibited
      lymphomatous conversion despite end stage intestinal stasis and recurrent
      obstruction, culminating in death. Our case calls into question some current
      assumptions about the prelymphomatous nature of this disease.

PMID- 11569711
TI  - Alagille syndrome with colonic polyposis.
AB  - Alagille syndrome is a rare inherited condition, which typically manifests during
      the first year of life as an episode of prolonged cholestasis. Although the
      pattern of inheritance is autosomal dominant with almost complete penetrance,
      highly variable expression may delay the diagnosis, and with passing time the
      clinical findings may be more difficult to recognize. This has clinical
      implications, as patients with Alagille syndrome are at risk for late
      complications such as hepatocellular carcinoma. We report a case of a 35-yr-old
      patient with Alagille syndrome who was diagnosed with colonic polyposis raising
      the possibility of an association between the two.

PMID- 11569712
TI  - Cyclosporine-Induced neurotoxicity during treatment of Crohn's disease: lack of
      correlation with previously reported risk factors.
AB  - A 13-yr-old boy with severe Crohn's disease was admitted with persistent
      hematochezia requiring transfusion. Cyclosporine A was begun on hospital day 22
      because of continued diarrhea and rectal bleeding despite high doses of i.v.
      corticosteroids. Six days into cyclosporine therapy, the patient developed
      multiple episodes of generalized tonic-clonic seizures accompanied with magnetic
      resonance imaging findings typical, although not pathognomonic, of cyclosporine A
      central nervous system neurotoxicity. Further investigations demonstrated that
      severe cyclosporine neurotoxicity may occur in the absence of previously reported
      clinical risk factors. Experience from the pediatric and adult GI transplant and
      neurological literature is discussed.

PMID- 11569713
TI  - Bleeding from cavernous angiomatosis of the rectum in Klippel-Trenaunay syndrome:
      report of three cases and literature review.
AB  - Klippel-Trenaunay syndrome (KTS) is a congenital vascular anomaly characterized
      by limb hypertrophy, cutaneous hemangiomas, and varicosities. GI hemorrhage is a
      potentially serious complication secondary to diffuse hemangiomatous involvement
      of the gut. We report on three patients with KTS who presented with transfusion
      dependent anemia and life-threatening bleeding due to extensive cavernous
      hemangiomas involving the rectum. Two patients were treated by proctocolectomy
      and coloanal anastomosis, which preserved anal function while controlling
      bleeding. The third patient required an abdominoperineal resection because of
      extensive rectal, perianal, and perineal angiomatosis. The literature on the
      evaluation and management of GI hemorrhage in KTS, particularly of colorectal
      origin, is reviewed.

PMID- 11569714
TI  - The hair of the dog.

PMID- 11569715
TI  - How do you like your quail prepared?

PMID- 11569716
TI  - Sonography of sigmoid diverticulitis: does sound make sense in this diagnosis?

PMID- 11569717
TI  - Re: Murphy et al.--Inflammatory response within Dukes' B colorectal cancer.

PMID- 11569718
TI  - Successful colonoscopic diagnosis of cecal cancer after failed barium enema.

PMID- 11569719
TI  - Disappearance of both MALT lymphoma and hyperplastic polyps in the stomach after
      eradication of Helicobacter pylori.

PMID- 11569720
TI  - Oral azathioprine for steroid refractory severe ulcerative colitis.

PMID- 11569721
TI  - Use of azathioprine or 6-mercaptopurine for treatment of steroid-dependent
      lymphocytic and collagenous colitis.

PMID- 11569722
TI  - GI bleeding from duodenal diverticula.

PMID- 11569723
TI  - Double stenting to prevent airway compression in proximal malignant esophageal
      strictures.

PMID- 11569724
TI  - A preliminary study of erythropoietin for anemia associated with ribavirin and
      interferon-alpha.

PMID- 11569725
TI  - Increasing incidence of celiac disease in India.

PMID- 11569726
TI  - Role of Campylobacter jejuni potential virulence genes in cecal colonization.
AB  - Campylobacter jejuni, a common commensal in chickens, is one of the leading
      causes of bacterial gastroenteritis in humans worldwide. The aims of this
      investigation were twofold. First, we sought to determine whether mutations in
      the C. jejuni ciaB and pldA virulence-associated genes impaired the organism's
      ability to colonize chickens. Second, we sought to determine if inoculation of
      chicks with C. jejuni mutants could confer protection from subsequent challenge
      with the C. jejuni wild-type strain. The C. jejuni ciaB gene encodes a secreted
      protein necessary for the maximal invasion of C. jejuni into cultured epithelial
      cells, and the pldA gene encodes a protein with phospholipase activity. Also
      included in this study were two additional C. jejuni mutants, one harboring a
      mutation in cadF and the other in dnaJ, with which we have previously performed
      colonization studies. In contrast to results with the parental C. jejuni strain,
      viable organisms were not recovered from any of the chicks inoculated with the C.
      jejuni mutants. To determine if chicks inoculated with the C. jejuni mutants
      become resistant to colonization by the C. jejuni parental strain upon subsequent
      challenge, chicks were inoculated either intraperitoneally (i.p.) or both orally
      and i.p. with the C. jejuni mutants. Inoculated birds were then orally challenged
      with the parental strain. Inoculation with the C. jejuni mutants did not provide
      protection from subsequent challenge with the wild-type strain. In addition,
      neither the C. jejuni parental nor the mutant strains caused any apparent
      morbidity or mortality of the chicks. We conclude that mutations in genes cadF,
      dnaJ, pldA, and ciaB impair the ability of C. jejuni to colonize the cecum, that
      chicks tolerate massive inoculation with these mutant strains, and that such
      inoculations do not provide biologically significant protection against
      colonization by the parental strain.

PMID- 11569727
TI  - Characterization of infectious laryngotracheitis virus isolates: demonstration of
      viral subpopulations within vaccine preparations.
AB  - Infectious laryngotracheitis (ILT) is a severe acute respiratory disease of
      chickens caused by ILT virus. To better understand the epidemiology of the
      disease, a polymerase chain reaction (PCR)-restriction fragment length
      polymorphism (RFLP) assay of the glycoprotein E gene has been developed and
      utilized to characterize vaccine strains and outbreak-related isolates. Enzymes
      EaeI and DdeI were used to differentiate the tissue culture origin (TCO) vaccine
      from chicken embryo origin (CEO) vaccines. Two RFLP patterns were observed with
      enzyme EaeI, one characteristic of the TCO vaccine and a second characteristic of
      all CEO vaccines. Three RFLP patterns were observed with enzyme DdeI. Patterns A
      and B were characterized as single patterns, whereas the type C pattern was a
      combination of patterns A and B. Analysis of vaccine strains showed the presence
      of patterns A and C. Pattern A was observed for the TCO vaccine and one CEO
      vaccine, whereas pattern C was observed for five of the six CEO vaccines
      analyzed. PCR-RFLP analysis of plaque-purified virus from pattern C CEO vaccine
      preparations demonstrated the presence of two populations (patterns A and B).
      Identification of molecularly different populations of viruses within currently
      used ILT vaccine is the first step to develop better molecular epidemiologic
      tools to track vaccine isolates in the field.

PMID- 11569728
TI  - Biological and molecular characterization of a pigeon paramyxovirus type-1
      isolate found in Argentina.
AB  - In this report, we describe the biological and molecular characterization of a
      paramyxovirus type-1 (PPMV-1) isolate found in wild pigeons in an urban habitat
      in Buenos Aires, Argentina. Of the nine pigeons captured, three were moribund,
      and the other six showed diarrhea, ataxia, tremor, torticolis, and wing
      paralysis. The intracerebral pathogenicity index was 1.29, and the amino acid
      (aa) sequence at the fusion protein cleavage site was 112GRQ KRF117. These
      characteristics correspond to a virulent Newcastle disease virus isolate.
      Nevertheless, it was not possible to reproduce the disease in chickens
      experimentally although the chickens exhibited seroconversion after inoculation.
      On the other hand, pigeons inoculated with the isolate became sick. These results
      provide further evidence about the unusual pathogenicity of PPMV-1 for chickens
      and show once more the need for more biological determinations in these cases to
      arrive at a final conclusion.

PMID- 11569729
TI  - Purification of a cross-protective antigen from Pasteurella multocida grown in
      vitro and in vivo.
AB  - A peptone-based medium was formulated to grow Pasteurella multocida in vitro,
      which expressed an antigen that induces cross protection in turkeys against
      different serotypes. Vaccines of various chromatographic fractions obtained from
      P. multocida grown in the medium induced active immune cross protection in
      turkeys, and sera from these turkeys passively cross protected naive poults. An
      antigen of approximately 39 kD molecular size was purified by preparative sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and electroelution from
      hydroxyapatite chromatographic fractions of both in vivo- and in vitro-grown P.
      multocida. The purified antigen from either source induced active immune cross
      protection but no passive protection in one of two experiments. Increasing the
      dose of vaccine resulted in both active and passive immune cross protection in
      the second experiment.

PMID- 11569730
TI  - Detection of avian pneumovirus in tissues and swab specimens from infected
      turkeys.
AB  - Conventional nested and TaqMan reverse transcription-polymerase chain reaction
      (RT-PCR) assays for the detection of avian pneumovirus (APV) were evaluated and
      compared with virus isolation (VI) for sensitivity and specificity. Respiratory
      tissues and tracheal swabs were collected from experimentally inoculated turkeys
      between 1 and 21 days postinoculation (DPI) and tested by all detection methods.
      APV was detected by both RT-PCR procedures as early as 1 DPI and as late as 17
      DPI, whereas virus was isolated only between 3 and 7 DPI. Pooled tracheal swab
      supernatant and dry swabs were excellent specimens for the detection of APV
      between 3 and 8 DPI. Turbinate and sinus specimens were the most productive
      samples over the entire collection period. Both RT-PCR assays were rapid and more
      sensitive than VI for the detection of APV in tissue and swab specimens from
      infected turkeys. RT-PCR allows for the rapid detection of APV from a variety of
      respiratory tissues as well as from dry swabs and tracheal swab supernatants.
      Antibody to APV was detected in 50% of the sampled APV-inoculated birds at 8 and
      9 DPI by enzyme-linked immunosorbent assay (ELISA). Early seroconversion (8-10
      DPI) allows antibody detection to be used as a screening tool for APV. Rapid and
      sensitive detection methods are needed for APV, a highly contagious disease
      affecting U.S. poultry.

PMID- 11569731
TI  - Protective efficacy of high-passage avian pneumovirus (APV/MN/turkey/1-a/97) in
      turkeys.
AB  - A U.S. isolate of avian pneumovirus (APV), APV/MN/turkey/1-a/97, was attenuated
      by serial cell culture passages in chicken embryo fibroblasts (seven passages)
      and Vero cells (34 passages). This virus was designated as APV passage 41 (P41)
      and was evaluated for use as a live vaccine in commercial turkey flocks. The
      vaccine was inoculated by nasal and ocular routes in 2-to-4-wk-old turkeys in 10
      turkey flocks, each with 20,000-50,000 birds. Only 2 birds per 1000 birds were
      inoculated in each flock with the expectation that bird-to-bird passage would
      help spread the infection from P41-exposed birds to their respective flock mates.
      The virus did spread from vaccinated birds to the entire flock within 10 days as
      detected by reverse transcription-polymerase chain reaction. Mild respiratory
      illness was observed in a few birds 12 days postvaccination in 2 of 10 flocks.
      Within 3 wk postvaccination, all flocks became seropositive for APV antibodies as
      measured by enzyme-linked immunosorbent assay. In an additional flock, the virus
      was administered to all turkeys simultaneously in drinking water and
      seroconversion occurred within 2 wk. All 11 flocks remained seropositive until 10
      wk postvaccination. When compared with unvaccinated flocks on the same farm from
      the previous year, the medication cost, total condemnation, and mortality rates
      attributed to APV were lower in P41-vaccinated flocks. When birds from vaccinated
      flocks were challenged with virulent APV under experimental conditions, no
      clinical signs were observed at 2, 6, and 10 wk postvaccination, whereas in the
      control unvaccinated birds, respiratory illness and virus shedding occurred after
      challenge. These results indicate that P41 administered by the nasal and ocular
      routes, and by drinking water, causes seroconversion and induces protection from
      virulent APV challenge for at least 10 wk.

PMID- 11569732
TI  - Pathology and histopathology of gossypol toxicity in broiler chicks.
AB  - Two experiments were conducted to determine the toxicity, pathology, and
      histopathology of purified gossypol in broiler chicks. Gossypol was added to
      broiler feed at 0, 100, 200, and 400 mg/kg of feed in Experiment 1 and at 0, 800,
      and 1600 mg/kg of feed in Experiment 2. Day-old broiler chicks were fed these
      diets from 1 to 21 days in Experiment 1 and from 1 to 23 days in Experiment 2. In
      Experiment 1, body weight and feed intake at 21 days were not significantly
      affected by dietary gossypol. However, chicks fed gossypol at 400 mg/kg of feed
      had poor feed conversion ratio compared with the other treatment. Feed conversion
      ratios were 1.493, 1.564, 1.471, and 1.60 for chicks fed gossypol at 0, 100, 200,
      and 400 mg/kg of feed, respectively (Experiment 1). Chicks fed 400 mg/kg gossypol
      also had mild perivascular lymphoid aggregate formations and bilary hyperplasia
      in the liver. In Experiment 2, gossypol at 1600 mg/kg resulted in 28.1%
      mortality. Gossypol at 800 and 1600 mg/kg feed resulted in significant decreases
      in body weight and feed intake of chicks. The average body weights of 23-day-old
      chicks in Experiment 2 were 676, 224, and 111 g for 0, 800, and 1600 mg/kg
      gossypol, respectively. Feed conversion ratios of chicks fed 800 and 1600 mg/kg
      gossypol were significantly higher than those of chicks fed control diets (1.383
      vs. 1.564 vs. 1.745 for 0, 800, and 1600 mg/kg gossypol, respectively). Plasma
      iron and hematocrit values were significantly reduced by gossypol at 800 and 1600
      mg/kg of feed. Enlarged gallbladder was the only gross pathology symptom
      associated with gossypol levels. Severe cases of perivascular lymphoid aggregate
      formation, biliary hyperplasia, and hepatic cholestasis were observed in chicks
      fed 800 and 1600 mg/kg of gossypol in feed. No gossypol-related changes were
      observed in kidney tissues of chicks. These results show that gossypol is toxic
      to broiler chicks at high levels. This study also shows that histopathologic
      changes in liver due to gossypol also occur at levels lower than the levels that
      affect body weight.

PMID- 11569733
TI  - A reverse transcriptase-polymerase chain reaction assay for detecting Highlands J
      virus.
AB  - Highlands J (HJ) virus is an arbovirus frequently recovered at high rates in
      mosquitoes collected in the eastern United States. HJ virus is primarily a
      veterinary pathogen causing disease in domestic birds including turkeys,
      chickens, and partridges. It has an enzootic cycle similar to eastern equine
      encephalitis (EEE) virus and is often used as an indicator species in EEE
      surveillance programs. Current immunologic techniques to identify HJ virus are
      often inefficient and can involve cross-reactivity of antibodies. Therefore, we
      developed a molecular-based assay by a reverse transcriptase (RT)-polymerase
      chain reaction (PCR) technique. Primers were constructed from conserved sequences
      of the E1 coding region from 19 strains of HJ virus. PCR amplifications from
      serial dilutions of HJ virus-infected Vero cell culture supernatants indicated
      that this assay could detect viral RNA at concentrations of 10 plaque-forming
      units per reaction. Extracted RNAs from western equine encephalitis, EEE,
      LaCrosse, and Jamestown Canyon viruses were not detected with this assay. RNA
      extracted directly from the brain tissue of a dead house sparrow and from a pool
      of Culiseta mosquitoes yielded a PCR product of the expected size. The RT-PCR
      technique developed was both sensitive and specific for detecting HJ virus from
      infected cell culture supernatants, bird brain tissues, and mosquitoes. This new
      assay will permit rapid and accurate diagnosis of HJ virus, both enhancing
      surveillance activities for EEE transmission risk and monitoring infections in
      domestic poultry and wild birds.

PMID- 11569734
TI  - Infectious bronchitis serology in broilers and broiler breeders: correlations
      between antibody titers and performance in vaccinated flocks.
AB  - In this study, a follow-up was made between 1993 and 1997 from broiler breeders
      at birth down to offspring broilers at processing, through vertically integrated
      registration of infectious bronchitis virus (IBV) antibody titers and performance
      data. All measurements were used two by two in a simple correlation study to
      calculate the degree to which they were linearly correlated. The antibody
      patterns in the broiler breeders indicated frequent field infections breaking
      through vaccinal immunity. Significant correlations measured between antibody
      titers and production parameters within and between the generations strongly
      suggested negative effects of IBV infections on laying percentage in the breeders
      and on mortality and daily weight gain in the broilers. Economic losses
      associated with IBV infections in the broilers occurred predominantly in flocks
      hatched with low and erratic maternal antibody titers. We concluded that IBV
      vaccination strategies should aim at high and uniform antibody titers in the
      broiler breeders.

PMID- 11569735
TI  - Molecular characterization of seven field isolates of infectious bursal disease
      virus obtained from commercial broiler chickens.
AB  - Specific-pathogen-free sentinel birds were used as an initial biological system
      to isolate infectious bursal disease virus (IBDV) field isolates from commercial
      broiler farms exhibiting recurrent respiratory problems and poor performance.
      Reverse transcription (RT)-polymerase chain reaction (PCR) was used to amplify a
      248-bp product encompassing the hypervariable region of the IBDV VP2 gene.
      Restriction fragment length polymorphism (RFLP) analysis of the RT-PCR products
      was performed with the restriction endonucleases DraI, SadI, TaqI, StyI, BstNI,
      and SspI. Two isolates (619 and 850) exhibited a RFLP pattern characteristic of
      Delaware variant E IBDV. Restriction enzyme digestion for four isolates (625,
      849, 853, and 11,153) revealed unmatched RFLP patterns when compared with
      reference IBDV strains. Nucleotide and deduced amino acid sequence analyses of
      the VP2 hypervariable region for these six isolates revealed identity (96.3% up
      to 98%) with Delaware E variant IBDV strain. However, serine at position 254,
      which is characteristic of Delaware variant strains, was substituted by
      asparagine in these six isolates. The seventh IBDV isolate (9109) also exhibited
      a unique RFLP pattern, which included the SspI restriction site, which is
      characteristic of very virulent (vv) IBDV strains. Nucleotide and amino acid
      sequence analyses of the hypervariable region for this isolate revealed identity
      (90%) with the standard challenge strain. However, the leucine residue at
      position 294 was substituted by isoleucine. This substitution corresponds to one
      of the amino acids that are conserved in the vvIBDV strains. Antigenic index
      studies of the predicted amino acid sequence of the hypervariable region of VP2
      from isolates 619, 625, 849, 850, 853, and 11,153 exhibited a profile almost
      identical to variant E, whereas the isolate 9109 exhibited a profile
      characteristic of standard IBDV strains.

PMID- 11569736
TI  - Combination of competitive exclusion and immunization with an attenuated live
      Salmonella vaccine strain in chickens.
AB  - To use the advantages of both the competitive exclusion (CE) technique and
      immunization with a live Salmonella vaccine, the combination of these methods was
      studied. Specific-pathogen-free chickens were pretreated by combined or single
      administration of a CE culture and a commercial live Salmonella typhimurium
      vaccine on days 1 and 2 of life and challenged with Salmonella typhimurium on day
      3 to study the exclusion effect by both the CE preparation and the Salmonella
      vaccine. The exclusion effect by the CE culture combined with the immunologic
      effect by the live vaccine was studied after challenge of the birds on day 43 of
      age. The number of challenge organisms in ceca was used to evaluate the efficacy
      of the pretreatment. The protective exclusion effect of the CE culture was
      substantial in very young chicks and still detectable in 6-wk-old birds. The
      attenuated Salmonella typhimurium vaccine produced only an initially occurring
      exclusion effect. Because the exclusion effect of the CE culture was considerably
      stronger than the exclusion effect of the attenuated Salmonella typhimurium
      vaccine, the combination of both did not result in an additive protective effect.
      In order to exploit the exclusion potential between Salmonella strains and to
      attain an additive exclusion effect by a CE culture and a vaccine strain, live
      Salmonella vaccines are needed that are sufficiently attenuated without affecting
      genes essential for colonization exclusion of other Salmonella organisms. In 6-wk
      old birds, the exclusion effect by the CE culture combined with the immunologic
      effect by the live Salmonella vaccine resulted in a degree of protection
      considerably beyond that generated by the exclusive use of the two methods. The
      administration of the live Salmonella vaccine strain prior to or simultaneously
      with the CE culture revealed the best protective effect because such combinations
      ensure an adequate persistence of the vaccine strain as prerequisite for the
      expression of an exclusion effect in very young chicks and the development of a
      strong immune response affording protection in older birds.

PMID- 11569737
TI  - Early posthatch protection against Marek's disease in chickens vaccinated in ovo
      with a CVI988 serotype 1 vaccine.
AB  - CVI988, a serotype 1 Marek's disease virus (MDV), was used as an in ovo vaccine
      in specific-pathogen-free chickens to determine if this virus induces early
      posthatch protection against Marek's disease as has been shown previously for
      turkey herpesvirus. MDV CVI988 was injected at embryonation day (ED) 17 (group 1)
      or at hatch (group 2). A third group (group 3) was left unvaccinated. At 1, 2, 3,
      4, 5, and 7 days of age, chickens from each group were sampled and examined as
      follows: a) single-cell suspensions of spleen were inoculated onto chicken embryo
      fibroblast monolayers to isolate the virus; b) sections of bursal tissues were
      stained by indirect immunofluorescence assays with anti-pp38 monoclonal antibody
      to identify viral antigen expression; and c) chickens were exposed intra
      abdominally to MDV RB1B, a virulent serotype 1 MDV. Results revealed that in
      chickens given MDV CVI988 at ED 17, virus and virus-encoded protein were not
      detected until chickens were 3 and 2 days old after hatching, respectively.
      Results also indicated that during the first 4 days after hatch, the chickens
      given MDV CVI988 at ED 17 were better protected against virulent MDV than those
      given MDV CVI988 at hatch (P < or = 0.001). These results suggested that MDV
      CVI988 proteins were adequately expressed in the embryo to initiate prehatch
      immunologic response. Additional efforts with more sensitive techniques than used
      in this study are needed to identify the nature of viral expression in embryos.

PMID- 11569738
TI  - Detection and persistence of infectious bursal disease virus in specific-pathogen
      free and commercial broiler chickens.
AB  - In an earlier study, specific-pathogen-free (SPF) chickens were inoculated with
      infectious bursal disease virus (IBDV) at 3 wk of age. Their bursas were examined
      for virus at different intervals postinoculation (PI) by reverse transcriptase
      (RT)/polymerase chain reaction (PCR) and by virus isolation in chicken embryos up
      to 21 days PI. The RT/PCR was positive, but attempts to isolate infectious virus
      from bursal homogenates failed. This prompted us to investigate the persistence
      of IBDV or its RNA in the bursa of Fabricius (BF) of inoculated and vaccinated
      SPF chicks and of inoculated and vaccinated commercial broiler chicks that have
      maternally derived antibodies. Four trials were conducted in SPF and commercial
      broiler chickens. Infectious virus was detected by embryo inoculation up to 7
      days PI in the BF of SPF chickens inoculated at 2 or 3 wk of age and up to 21
      days PI by RT/PCR, whereas the viral RNA was detected by RT/PCR for up to 28 days
      PI. In SPF chicks inoculated at 1 day of age, the bursa-derived virus or its RNA
      was detected at 7 and 14 days PI when inoculated at a high dose (10(4) mean
      embryo infective dose [EID50]/bird) or at a low dose (10(2.5) EID50/bird). In
      commercial 1-day-old broiler chicks, the bursa-derived virus was detected at 7
      and 14 days PI when inoculated at a high dose (10(4) EID50/bird), whereas the
      virus was detected only at 14 days PI when inoculated at a low dose (10(2.5)
      EID50/bird). In SPF and commercial chicks vaccinated with a modified live IBDV
      vaccine, the virus or its RNA was detected at 7 and 14 days postvaccination in
      SPF chicks, but neither the live vaccine virus nor its RNA was detected in
      commercial broilers vaccinated at 1 day or 2 wk of age.

PMID- 11569739
TI  - Pathogenicity and drug susceptibility of the Pasteurella anatis isolated in
      chickens in Taiwan.
AB  - A strain of Pasteurella anatis (PA) was isolated from the sinus of an adult
      leghorn laying chicken with sinusitis, nasal discharge, drop in egg production,
      and low mortality, symptoms initially thought to indicate infectious coryza. The
      tiny, smooth, whitish colonies were identified as PA. To compare its
      pathogenicity with that of commercial broilers, nine groups, 10 birds per group,
      of 10-day-old broilers were individually inoculated with the strain of PA,
      Pasteurella multocida (PM), or Escherichia coli (EC) by intravenous,
      intraperitoneal, intramuscular, or subcutaneous inoculation. The PA was
      determined to cause the signs, lesions, and septicemic death, which are similar
      to the symptoms of PM or EC infection. At 1 wk postinfection (PI), the mortality
      rate was between that of PM and EC infection at 1 wk PI. Twenty antimicrobial
      containing discs were evaluated, and the isolate was highly sensitive to
      cetiofer, amoxicillin, lincopectin, and furazolidone. Furthermore, it was
      moderately sensitive to tetracycline and enrofloxacin and only slightly sensitive
      to cephalothin, chloramphenicol, flumequine, nalidixic acid, neomycin, oxolinic
      acid, streptomycin, and trimethoprim. The PA infection was treated successfully
      with amoxicillin.

PMID- 11569740
TI  - Differences in the pathogenicity of various bacterial isolates used in an
      induction model for gangrenous dermatitis in broiler chickens.
AB  - A gangrenous dermatitis model was developed in broiler chickens, in which birds
      previously vaccinated at 14 days of age with a bursal disease virus vaccine were
      challenged at 4 wk of age with various bacterial combinations with the
      combination of subcutaneous and intramuscular injection. Gangrenous dermatitis
      lesions were not produced in birds injected with one of the Staphylococcus aureus
      isolates, either alone or in combination with various Clostridium septicum
      isolates. Other S. aureus isolates produced significant levels of gangrenous
      dermatitis either alone or in combination with the same C. septicum isolates.
      These same C. septicum isolates when given alone did not produce gangrenous
      lesions. Data from this experiment show the highest level of mortality occurred
      in birds challenged with a mixture of C. septicum and S. aureus isolates, whereas
      lower or no mortality was associated with the same isolates given separately. The
      data clearly demonstrate that the pathogenicity of isolates responsible for
      gangrenous dermatitis varies widely, indicating that the frequency and severity
      of lesion production, as well as the occurrence of mortality, are largely
      dependent upon the specific isolate or isolates with which the birds are
      challenged.

PMID- 11569741
TI  - Reticuloendotheliosis virus integration in the fowl poxvirus genome: not a recent
      event.
AB  - Integration of reticuloendotheliosis virus (REV) into the genome of fowl poxvirus
      (FPV) has been reported recently. With a view to determine whether this event had
      occurred in the past, we screened by polymerase chain reaction (PCR) for the
      presence of REV provirus in the DNAs of nine avian poxviruses, some of which had
      been lyophilized 50 yr ago. For REV, 5' long terminal repeat (LTR) and REV
      envelope sequences were amplified, whereas for FPV, the major envelope antigen
      gene and the region flanking REV sequences were amplified. In six of seven FPV
      strains examined, the specific PCR amplicons were obtained for both REV provirus
      and FPV sequences. One isolate in which presence of REV 5' LTR and envelope was
      not detected by PCR, a LTR remnant was detected by Southern hybridization.
      Interestingly, no REV sequence was detected in either canary poxvirus or pigeon
      poxvirus genome. These observations indicate that REV integration in the FPV
      genome is not a recent phenomenon but probably occurred prior to 1949.

PMID- 11569742
TI  - Genotypic and phenotypic characterization of potential virulence of intestinal
      avian Escherichia coli strains isolated in Algeria.
AB  - In order to characterize potential pathogenic Escherichia coli strains isolated
      from diarrheic hens and chickens originating from intensive battery rearing in
      North Algeria, the presence of a large range of virulence factors and markers was
      studied in 50 strains by DNA-DNA hybridization on colonies and phenotypic tests.
      The sequences we focused on were those coding for adhesins F5, F41, F17, Pap,
      Afa, and Sfa; intimin Eae; and toxins STa, STb, LT1, Stx1, Stx2, CNF1, and CNF2.
      The phenotypes explored were the colicins, aerobactin, hemolysins, and
      hemagglutinin production and serum resistance. The genotypic and phenotypic tests
      enabled us to categorize the isolates into two distinct groups: those with a
      potential to invade the host (27 strains were serum resistant and/or produced
      aerobactin), among which three strains were also potentially diarrheagenic, one
      strain was LT1 + F17+ Afa+ Pap+ (enterotoxigenic E. coli) and the two others were
      Stx1 (verotoxigenic E. coli). Twenty-three strains were colicinogenic, including
      19 strains producing colicin V. This latter factor was also detected in isolates
      negative for the other virulence factors. On the basis of the type of
      erythrocytes agglutinated, we established 14 mannose-resistant hemagglutination
      patterns among the 37 strains tested, including 22 serum-resistant and/or
      aerobactin producing strains and 15 strains negative for these two characters.
      None of the strains produced alpha hemolysin, whereas two strains produced beta
      hemolysin and enterohemolysin, respectively. Congo red fixation was observed in
      25 strains. No relationship could be detected between Congo red fixation and the
      presence of other virulence markers, such as serum resistance and aerobactin
      production. This study shows that among isolates originating from the feces of
      diarrheic chickens, the proportion of potentially diarrheagenic E. coli strains
      is low.

PMID- 11569743
TI  - Serotyping of Haemophilus paragallinarum isolates from Mexico by the Kume
      hemagglutinin scheme.
AB  - A total of 42 isolates of Haemophilus paragallinarum from Mexico were serotyped
      by the Kume hemagglutinin scheme. Serovars A-1, A-2, B-1, and C-2 were recognized
      among 11 (26.2%), 7 (16.6%), 4 (9.5%), and 14 (33.3%) isolates, respectively. A
      further six isolates (14.3%) showed hemagglutinating activity but could not be
      classified into any serovar. Commercial vaccines containing Kume serovars A-1, A
      2, B-1, and C-2 may provide better protection than those bi- or trivalent
      infectious coryza vaccines currently used in Mexico.

PMID- 11569744
TI  - Aerosolization of Newcastle disease vaccine virus and Enterococcus faecalis.
AB  - In order to study the aerosol transmission of arthropathic and amyloidogenic
      Enterococcus faecalis strains, preliminary aerosol experiments were performed.
      The experiments were carried out in empty isolators to assess the yield and
      viability of E. faecalis and Newcastle disease vaccine virus (NDVV) aerosol
      particles with time. NDVV was aerosolized because this virus would be used in
      combination with E. faecalis in a subsequent study. Concentrations of about 10(5)
      colony-forming units (CFU) of E. faecalis/ml of air were still found 30 min after
      the aerosol application. At 45 min, however, E. faecalis concentrations dropped
      below the detection level. The average E. faecalis concentration during the
      aerosol experiment was estimated at 10(5) CFU/liter. The NDVV aerosol generated
      an average of 10(4)-10(5) 50% embryo infective dose per liter of air. In these
      experiments, E. faecalis and NDVV aerosols were successfully generated despite
      considerable initial particle loss. The bacteria and virus uptakes per chick are
      discussed in case day-old chicks would be exposed to these aerosols.

PMID- 11569745
TI  - Retrospective ultramicroscopic investigation on naturally cryptosporidial
      infected commercial turkey poults.
AB  - The morphometric characteristics and the ultramicroscopic findings of
      Cryptosporidium spp. at various stages of their life cycle in the intestinal and
      bursal epithelial cells of naturally infected 30-day-old commercial turkeys are
      reported. Small, sporulated oocysts, observed in the small intestinal content
      after flotation, were identified as Cryptosporidium meleagridis on the basis of
      morphometric characteristics (round in shape and 4.5-5.0 microm in size) and the
      small intestinal localization. Light section examinations revealed the presence
      of the protozoon in multiple organs, but its prevalence was highest in the
      intestinal and bursal epithelial cells. Ultramicroscopic studies on ileum and
      bursal samples showed the presence of all the life cycle stages in the
      microvillar brush epithelial cells in both the organs examined. On the basis of
      the comparison of the morphology and the sizes of the microorganisms parasitizing
      the ileum and the bursa, hypotheses are considered on the possible species
      involved.

PMID- 11569746
TI  - Prevalence of Salmonella, Campylobacter, and Escherichia coli on ostrich
      carcasses and the susceptibility of ostrich-origin E. coli isolates to various
      antibiotics.
AB  - There has been limited research on the prevalence of foodborne pathogens such as
      Escherichia coli O157:H7, Salmonella, and Campylobacter on ostrich carcasses.
      Likewise, few studies have been done in ostriches to determine the antimicrobial
      susceptibilities of common bacteria, like E. coli. In this study, ostrich
      carcasses were sampled from eight slaughterhouses in Ohio and one in Indiana.
      Although results demonstrated no E. coli O157:H7 from the carcasses sampled, 91%
      (116/128) of the dressed carcasses sampled had E. coli present. One carcass
      sample (1/152) was positive for Salmonella. Campylobacter were detected in 10%
      (19/191) of the carcasses. Antimicrobial susceptibility testing on 93 carcass E.
      coli isolates showed resistance to erythromycin (99%), neomycin (65%), netilmicin
      (2%), oxytetracycline (22%), streptomycin (2%), and trimethoprim (3%). All
      isolates were resistant to bacitracin, lincomycin, penicillin, and vancomycin.
      For the large intestinal sampling, 149 of the 217 (69%) samples had E. coli
      present. Fifty of these 149 samples had E. coli levels ranging from 10(2) to
      10(5) colony-forming units/g feces. Campylobacter were isolated from 6 of 201
      (3%) samples. No Salmonella colony was detected. Antimicrobial susceptibility
      testing on 131 intestinal E. coli isolates showed resistance to erythromycin
      (98%), neomycin (66%), netilmicin (34%), oxytetracycline (34%), streptomycin
      (40%), and trimethoprim (13%). All isolates were resistant to bacitracin,
      lincomycin, penicillin, and vancomycin.

PMID- 11569748
TI  - Epidemiology and significance of chicken infectious anemia virus infections in
      broilers and broiler parents under nonvaccinated European circumstances.
AB  - A serologic survey in unvaccinated broiler parent and broiler progeny flocks
      demonstrated seroconversion against chicken infecrious anemia virus (CIAV) in all
      parent flocks before or around point of lay and in 38% of the broiler flocks
      examined at slaughter age. The presence of CIAV antibodies at slaughter of
      broilers was positively correlated with slaughterhouse condemnation rates.
      Results indicate that CIAV infections are highly prevalent in both broiler parent
      and broiler flocks and that CIAV infections in broilers are associated with
      increased slaughterhouse condemnation.

PMID- 11569747
TI  - Use of a genetic marker for wild-type potentially pathogenic infectious bursal
      disease viruses.
AB  - An amino acid mutation at residue 284 (Ala to Thr) in the VP2 protein of
      infectious bursal disease viruses (IBDVs) has been correlated with the ability to
      replicate in cell culture. In this study, we designed a molecular test for this
      mutation. The reverse transcriptase/polymerase chain reaction (RT/PCR) was used
      to amplify a 743-bp region of the VP2 gene that contained the codon for amino
      acid 284. The restriction endonuclease NgoMIV was selected for this study because
      the first three nucleotides of its six-base recognition sequence are the codon
      responsible for the amino acid alanine at residue 284. The RT/PCR products from
      10 known pathogenic and 16 vaccine strains of IBDV were examined for the presence
      or absence of the NgoMIV site. We also examined 189 field strains of IBDV for the
      NgoMIV site. All 10 known pathogenic IBDV strains contained the NgoMIV site,
      indicating they contained alanine at residue 284. None of the vaccine strains had
      the NgoMIV site, suggesting they had threonine or another amino acid at residue
      284. The results suggest that the presence of this NgoMIV site can be used as a
      marker for the identification of wild-type (nonvaccine) IBDV strains. The RT/PCR
      products from 152 (80.4%) of the field strains had the NgoMIV site and thus have
      the potential to be wild-type pathogenic viruses. The RT/PCR products from 37
      (19.6%) of the field strains were not cleaved by NgoMIV and thus are potentially
      attenuated vaccine strains. Molecular diagnostic assays have been used to place
      IBDV strains into genetically related groups. The identification of this genetic
      marker now makes it possible to identify viruses that are wild-type strains that
      have the potential to be pathogenic viruses.

PMID- 11569749
TI  - Experimental inoculation of European starlings (Sturnus vulgaris) and American
      crows (Corvus brachyrhynchos) with Mycobacterium bovis.
AB  - The purpose of this series of pilot studies was to determine whether the
      passerine species studied are susceptible to infection with Mycobacterium bovis.
      Separate experiments were conducted on wild-caught starlings (Sturnus vulgaris)
      and American crows (Corvus brachyrhynchos). In each experiment, four birds were
      challenged intraperitoneally and four were challenged orally with microorganisms.
      Challenge dose was 1 x 10(5) colony-forming units of M. bovis cultured from a
      white-tailed deer (Odocoileus virginianus) case in Michigan. Birds were
      euthanatized at 1 and 2 mo postinoculation. Histologic lesions suggestive of
      mycobacteriosis, without the presence of acid-fast bacilli, were noted in all
      experimental groups. Mycobacterial cultures performed on pooled tissue samples
      were positive for M. bovis in only some of the intraperitoneal inoculates of each
      species.

PMID- 11569750
TI  - Poor serologic response to upper respiratory infection with Mycoplasma synoviae
      in turkeys.
AB  - Mycoplasma synoviae (MS) was isolated from a flock of commercial tom turkeys in
      which a small percentage of the birds exhibited clinical signs and lesions
      typical of MS synovitis. However, serologic testing of such flocks revealed poor
      to inconsistent reactivity by agglutination, enzyme-linked immunosorbent assay
      (ELISA) or hemagglutination inhibition; isolation of MS from such flocks proved
      to be very difficult. Turkeys were challenged with one of the isolates (K4463B)
      either by aerosol or systemically by a combination of intravenous, foot pad, and
      eyedrop routes. Turkeys challenged by the systemic route responded normally to
      all serologic tests, whereas those challenged by aerosol either responded very
      poorly on all serologic tests or were seronegative up to 6 wk postchallenge even
      though they were positive for MS by tracheal culture. These results suggest that
      turkeys may harbor an upper respiratory infection with MS while remaining
      serologically negative.

PMID- 11569751
TI  - A field study of naturally occurring specific antibodies against Clostridium
      perfringens alpha toxin in Norwegian broiler flocks.
AB  - Necrotic enteritis (NE), a disease associated with high numbers of the intestinal
      bacterium Clostridium perfringens, is common in intensive broiler production.
      Antimicrobial feed additives may control the disease, but their use is now being
      questioned in many countries. A field study was undertaken at the end of 1997 to
      study the level of naturally occurring specific humoral immunity against
      phospholipase C (PLC; C perfringens alpha toxin) in Norwegian broiler flocks.
      Blood samples were collected at hatch from 61 study flocks, and the sampling was
      repeated for 56 of the same flocks at processing. The level of specific
      antibodies against PLC was analyzed in an enzyme-linked immunosorbent assay
      (ELISA) test. Data on production performance and weekly mortality were recorded.
      The relationship between the age of the hens and the level of specific maternal
      antibodies in the progenies was studied. The association between the level of the
      maternal antibodies and the production performance, including mortality, was
      analyzed. The level of specific antibodies against PLC in day-old broiler flocks
      was relatively high and varied considerably compared with the levels in the
      broilers at processing. The progenies from the oldest hens had significantly
      higher levels of specific antibodies than the chicks from younger hens. No
      outbreak of NE occurred during the study period, making it impossible to analyze
      the association between naturally occurring specific immunity against PLC and the
      occurrence of the disease. However, the results showed that the flocks with high
      titers of specific maternal antibodies against PLC had lower mortality during the
      production period than flocks with low titers.

PMID- 11569752
TI  - Elevation of muscle and plasma 3-methylhistidine as a result of turkey
      coccidiosis.
AB  - To assess muscle breakdown during avian coccidiosis, the level of the non
      metabolizable amino acid 3-methylhistidine (3MH) was determined in muscle and
      plasma from turkey poults that received an infection with a field isolate
      containing a mixture of Eimeria species. The effect of increased levels of
      parasitism was evaluated at 6 days postinoculation (DPI) in birds receiving 2.5 x
      10(4), 1 x 10(5), or 2 x 10(5) oocysts each. The changes in 3MH levels during
      recovery from acute infection were assessed at 6-29 DPI in animals given 1.9 x
      10(5) oocysts per bird. In some experiments, uninoculated birds given the same
      amount of feed as infected birds (pair fed) were used to determine the impact of
      feed deprivation on weight loss and 3MH levels. Infected birds had significantly
      elevated plasma and muscle 3MH at 6 DPI after a single dose of Eimeria oocysts.
      The plasma and muscle 3MH returned to control levels after 14 DPI. The 3MH levels
      increased with increased dose of oocysts. Plasma and muscle 3MH levels were well
      correlated, and an inverse curvilinear relationship between weight gain and
      plasma 3MH concentrations levels was observed. Plasma and muscle 3MH levels were
      significantly elevated in pair-fed birds, but 3MH levels in infected birds were
      increased by 30% over pair-fed birds. The results suggested that muscle
      breakdown, as assessed by plasma and muscle levels of 3MH, increased during the
      acute stage of Eimeria infection in turkey poults.

PMID- 11569753
TI  - Sudden death of a bearded vulture (Gypaetus barbatus) possibly caused by
      Newcastle disease virus.
AB  - An adult female bearded vulture (Gypaetus barbatus) in the Tel Aviv University
      Research Zoo was found dead without previous clinical signs. The predominant
      pathologic changes were considerable bloody content in the intestines and
      enlargement of the liver, which had a rubbery consistency with color changes.
      Microscopic lesions consisted of multifocal histiocytic infiltration in the
      liver. Newcastle disease virus (NDV) was isolated from a cloacal swab and from
      the lungs and liver. Intracerebral pathogenicity index of the virus, as estimated
      in 1-day-old chicks, was repeated three times and had an average value of 1.68,
      indicating a velogenic strain. Numerous Clostridium septicum bacteria were found
      on the intestinal surface, but bioassays in which they were orally administered
      into chickens and mice revealed that, even though they were heavily multiplied in
      the intestines, they were nonpathogenic. It seems that NDV, documented for the
      first time in a bearded vulture in Israel, was the likely cause of sudden death.

PMID- 11569754
TI  - Cases of swollen head syndrome in broiler chickens in Greece.
AB  - From 50 commercial broiler flocks included in a study concerning respiratory
      disease, signs of swollen head syndrome (SHS) were shown in eight. Postmortem
      examination was performed in eight birds showing signs of SHS from each flock.
      The trachea and head from each bird were collected for laboratory investigation.
      An enzyme-linked immunosorbent assay (ELISA) was used for the detection of viral
      and avian mycoplasma antigens in the trachea, and bacteriologic examinations were
      performed from the infraorbital sinuses of the infected birds. According to the
      ELISA results, the most frequently detected antigen in the trachea was Mycoplasma
      synoviae (six flocks, 75%), followed by infectious bronchitis virus (IBV) (five
      flocks, 62.5%), avian adenovirus (four flocks, 50%), avian reovirus (three
      flocks, 37.5%), Mycoplasma gallisepticum (one flock, 12.5%), and Newcastle
      disease virus (NDV) (one flock, 12.5%). Turkey rhinotracheitis (TRT), infectious
      laryngotracheitis, and avian influenza viral antigens were not detected.
      Experimental assays for characterization of NDV and IBV isolates showed that they
      were strains of low virulence (evidently vaccine strains). Bacteriologic
      examinations from the infraorbital sinuses of the affected birds resulted in the
      isolation of Escherichia coli (seven cases, 87.5%) and Staphylococcus spp. (one
      case, 12.5%). It is evident that TRT virus did not play a causal role in SHS in
      commercial broiler flocks in Greece, but in this condition, other viruses (IBV,
      NDV), mycoplasmas, or bacteria may be involved, and environmental conditions seem
      to be essential to the occurrence and severity of the disease.

PMID- 11569755
TI  - Gizzard nematodiasis in Japanese mountain hawk eagle (Spizaetus nipalensis).
AB  - In this paper, we report spontaneous gizzard nematodiasis in an adult Japanese
      mountain hawk eagle (Spizaetus nipalensis). Grossly, the gizzard had a black
      mucoid substance attached to the surface mucous membrane, and the heart was
      dilated. Histologically, immature larvae with yellow pigments invaded crypts of
      the mucous membrane. More developed larvae invaded the lamina propria and
      muscular layers and serosa of the gizzard, with pressure atrophy and cellular
      reaction (infiltration of heterophils and macrophages and proliferation of
      fibrous connective tissue). Moderate bronchopneumonia due to larvae invasion was
      also seen in the lung. The morphology suggests that the parasites may be
      nematodes, but the species of nematode could not be confirmed. The bird may have
      died from malabsorption and respiratory damage as a result of the gizzard and
      lung lesions.

PMID- 11569756
TI  - Tuberculosis in geese (Anser anser) in Turkey.
AB  - Tuberculosis was detected in seven geese at the breeding unit of the Faculty of
      Veterinary Medicine, Kafkas University, during 1998. In the necropsy, lesions of
      nodular type were seen in the liver, spleen, and lungs. Histopathologically, the
      lesions were characterized by central areas of caseous necrosis surrounded by
      epithelioid cells, multinucleated giant cells, lymphocytes, and an outer fibrous
      capsule. Acid-fast bacilli were visualized by the Ziehl-Neelsen staining method
      in paraffin sections and smears. Inoculation into Lowenstein-Jensen media with
      glycerin yielded Mycobacterium spp.

PMID- 11569757
TI  - Enteritis as a cause of mortality in the western bluebird (Sialia mexicana).
AB  - Increased mortalities in adult western bluebirds utilizing nestboxes were noted
      in western Oregon during 1998 and 1999. A necrohemorrhagic enteritis was found in
      8 of 10 birds submitted for necropsy. Acanthocephalan parasites were present in
      four of eight birds with enteritis. Microscopic changes consistent with necrotic
      or ulcerative enteritis were commonly present. Anaerobic culture of the intestine
      yielded Clostridium perfringens in three of three birds. Genotype analysis of two
      of these isolates revealed them to be C. perfringens type A. Bacterial enteritis
      is believed to be the cause of the increased mortality rate, but further
      investigation is required to prove a definitive link to a clostridial agent.

PMID- 11569758
TI  - An age-embedding effect: time sensitivity and time insensitivity when pricing
      health benefits.
AB  - Benefits are often extended over time. One determinant of this benefit duration
      is how long a person will live to enjoy them. In four studies, we investigated
      whether people are sensitive to age when pricing benefits that will last for the
      remainder of one's life. In Study 1 drivers gave their willingness-to-pay (WTP)
      to cure a medical condition which would stop them from driving. Results showed an
      age-embedding effect: WTP was unrelated to the estimated number of driving years
      left. Study 2 tested whether age-embedding arose because people have a lot of
      information about themselves which dilutes the impact of age on their valuations.
      In Studies 3 and 4 we investigated whether people believed that age was an
      important consideration, or if they failed to properly incorporate it into their
      judgment. Results indicate that little weight is given to age when making
      individual pricing decisions, although people did not believe it was normatively
      irrelevant.

PMID- 11569759
TI  - Temporal factors in resource dilemmas.
AB  - The conflict between present and future consumption lies at the heart of resource
      dilemmas (RDs), yet the role of time has received little attention in this
      research area. Emphasis was on factors related to the social rather than the
      temporal conflict inherent in an RD. We propose a model that deals explicitly
      with the temporal distribution of outcomes. The model combines three basic
      elements: a simple algebraic model, representing the RD's payoff structure; a
      growth function, reflecting the autonomous growth of the resource pool; and a
      discount function, describing how the temporal distance of outcomes affects their
      perceived value. The model provides a comprehensive framework for understanding
      the role of temporal factors in RD situations. It enables us to identify four
      relevant temporal RD characteristics (people's discount rates, their time
      horizon, the inter-trial delay, and the pool's growth rate) and to describe how
      these would be expected to affect people's tendency to cooperate. Theoretical,
      methodological and practical implications of the work are briefly discussed.

PMID- 11569760
TI  - The role of cognitive resources in the valuation of near and far future events.
AB  - People's behaviors often appear short-sighted, suggesting they overvalue the near
      future and undervalue the far future. In three experiments, the present research
      focussed on the role of cognitive resources in the valuation of near and distant
      future events. Experiment 1 tested a new discounting paradigm for use in the
      subsequent experiments. Experiments 2 and 3 used different manipulations (time
      pressure and a concurrent tone task) to restrict the cognitive resources of
      participants valuing a series of future events. In both experiments, this
      manipulation caused an increase in the valuation of far future events but not in
      the valuations of near future events. Implications of these findings for the role
      of cognitive resources in time discounting processes are briefly discussed.

PMID- 11569761
TI  - Time is on my side: optimism in intertemporal choice.
AB  - The present research examines the role of optimism on time preferences for both
      losses and gains. It is argued that optimism has asymmetric effects on time
      preferences for gains versus losses: one reason why decision makers prefer
      immediate gains is because they are optimistic that these gains will be followed
      by additional gains in future. In contrast, decision makers prefer to delay
      losses because they are optimistic that losses are avoidable in the future.
      Optimism about outcomes affects time preferences for both gains and losses, such
      that low optimism reduces the discount rates while increased optimism is
      associated with higher discount rates. This prediction was supported in two
      different domains: monetary outcomes (Study 1), and health (Study 2).
      Implications of these results for both research practice and time preferences in
      the real world are discussed.

PMID- 11569762
TI  - A timely account of the role of duration in decision making.
AB  - The current work takes a general perspective on the role of time in decision
      making. There are many different relationships and interactions between time and
      decision making, and no single summary can do justice to this topic. In this
      paper we will describe a few of the aspects in which time and decision making are
      interleaved: (a) temporal perspectives of decisions--the various temporal
      orientations that decision-makers may adopt while making decisions, and the
      impact of such temporal orientations on the decision process and its outcomes;
      (b) time as a medium within which decisions take place--the nature of decision
      processes that occur along time; (c) time as a resource and as a contextual
      factor--the implications of shortage in time resources and the impact of time
      limits on decision making processes and performance; (d) time as a commodity-
      time as the subject matter of decision making. The paper ends with a few general
      questions on the role of duration in decision making.

PMID- 11569763
TI  - On the psychology of time preference and human decisions: introduction to the
      special issue.

PMID- 11569764
TI  - Time preferences for the very long term.
AB  - Many important decisions concern outcomes delayed by decades or centuries.
      Whereas some economists have argued that inter-generational discount rates should
      be lower than intra-generational rates, three experiments found that inter- and
      intra-generational discount rates were quite similar. Experiment 1 found that
      discount rates for long delays (30-900 years) were lower than those for shorter
      delays (1-30 years) but that, holding delay constant, discount rates for outcomes
      occurring to future generations were similar to those for outcomes occurring to
      the present generation. Experiment 2 compared inter-generational discount rates
      for three different types of outcomes and found similar discount rates for saving
      lives, improving health, and financial benefits. Experiment 3 found similar inter
      generational discounting of life-saving programs that benefit people close to or
      distant from the decision maker. These studies indicate that the discount rate
      applied to outcomes occurring to future generations depends on the length of the
      time delay but not on other factors.

PMID- 11569765
TI  - Use of laminar cup liners for the preparation of fatty samples for pesticide
      analysis.
AB  - Residue analyses have been developed for hundreds of pesticides and their
      metabolites in foods. Normally, the fat is extracted with a non-polar solvent,
      followed by a re-extraction of the analytes into a polar solvent, removal of the
      remaining fat by several clean-up steps and finally determination by gas
      chromatography (GC). Over the last 3 years, experience has been gained in the use
      of laminar cup liners for GC injectors. The geometry of the laminar cup liner
      allows the injection of sample extracts with a residual fat content of tip to 5%.
      The cup prevents fatty compounds entering the capillary GC column. Using this
      approach, several residue methods can be simplified without losing precision or
      recovery. The preparation of the samples, such as cows milk, human milk, avocado
      and cosmetics can be reduced to one solvent extraction step with petroleum ether
      and one single cleanup step with an Extrelut column. No further clean up with
      Florisil or GPC is then necessary. The proposed method using a laminar cup and
      GC/ECD has been tested for the analysis of organochlorine and organophosphorous
      pesticides, PCBs, nitro-musk fragrances, together with pyrethroids and pyrethrins
      in the above matrices. Polycyclic musk substitutes were analysed by GC/MS.

PMID- 11569766
TI  - Method validation for strobilurin fungicides in cereals and fruit.
AB  - Strobilurins are a new class of fungicides that are active against a broad
      spectrum of fungi. In the present work a GC method for analysis of strobilurin
      fungicides was validated. The method was based on, extraction with ethyl
      acetate/cyclohexane, clean-up by gel permeation chromatography, (GPC) and
      determination of the content by gas chromatography (GC) with electron capture (EC
      ), nitrogen/phosphorous (NP-), and mass spectrometric (MS-) detection. Three
      strobilurins, azoxystrobin, kresoxim-methyl and trifloxystrobin were validated on
      three matrices, wheat, apple and grapes. The validation was based on recovery
      tests at three or four spiking levels, determined as double determinations and
      repeated three times (n = 6). The mean recoveries for the three detectors were in
      the range of 70-114%, and the LODs were between 0.004 mg/kg and 0.014 mg/kg, for
      all three strobilurins. The values for repeatability and reproducibility were
      within the limits for repeatability and reproducibility given by the Horwitz
      equation. Validation was not accepted for azoxystrobin in grapes on all three
      detectors and for azoxystrobin in apple for the MS-detector. A comparison of
      matrix-matched standards versus standards in solvent showed varying differences
      between the two calibration curves.

PMID- 11569767
TI  - European standardization of methods for pesticide residue analysis in foods-
      current status.
AB  - The aim of this paper is to inform all scientists working in pesticide residue
      analysis on the contents, size and background of European standards (ENs) in this
      area. These ENs were established by a Technical Committee (TC 275, of the
      European Committee for Standardization (CEN, and each CEN member country is
      obliged to implement them as national standards. EN 1528:1996 comprises eight
      methods for the multiresidue determination of organochlorine pesticides and
      polychlorinated biphenyls (PCBs) in fatty foods. For non-fatty foods such as
      fruits and vegetables, EN 12 393:1998 provides five multi-residue methods. In
      addition, three methods for dithiocarbamate fungicides in EN 12 396: 1998/2000
      and two methods for bromide residues in EN 13 191:2000 are already available. In
      this way, a valuable harmonization of methods across Europe is achieved which is
      useful for quality control in the food industry as well as in official food
      inspection.

PMID- 11569768
TI  - Pesticide residues in grapes and wine in Italy.
AB  - Two hundred and one pesticides comprising 84 fungicides, 88 insecticides and 29
      herbicides are registered in Italy for use on grapes. Recently, the maximum
      residue limits (MRLs) for 16 fungicides and five insecticides were established
      for wine. However, literature data shows that some MRLs for wine are not
      consistent with the corresponding values for grapes. In Italy, the Ministry of
      Health has the responsibility for checking pesticide contamination in fruit and
      vegetables in general distribution (i.e. grocery shops, food stores). From 1996
      to 1999, out of 1532 grape samples analysed, levels of 1.0, 0.9, 1.8 and 1.9% in
      each year respectively were contaminated. As part of the National Residue
      Monitoring Programme, the Ministry of Agriculture carried out investigations of
      samples collected directly from the field (therefore of a known pesticide
      treatment history) in order to find the causes of the observed irregularities and
      to identify preventative measures. In 1996, 1998 and 1999, out of 481, 1195 and
      1949 grape samples analysed, 7.9, 6.5 and 2.5% respectively were contaminated,
      while no residues were detected in 259 wine samples. The National Observatory on
      Pesticide Residues collects data from analyses performed by highly reliable, non
      institutional laboratories on samples from farming cooperatives or individual
      forms, food companies, wholesale and retail markets. Of the 846 grapes samples
      and 190 wine samples collected in 1998 and 1999, a total of 6.1 and 2.1%
      respectively of grapes and 0% for all wine samples were found to contain
      residues.

PMID- 11569769
TI  - Residues of aldicarb in oranges: a unit-to-unit variability study.
AB  - Residues of aldicarb and its sulphoxide and sulphone oxidative metabolites in
      individual Navelino orange trees were determined at several time intervals after
      soil application of TEMIK 10G at 200 g formulated material per tree. Analysis was
      by HPLC with postcolumn derivatization giving average recoveries of 98% for
      aldicarb (RSD 6%), 34% for aldicarb sulphoxide (RSD 5%) and 77% for aldicarb
      sulphone (RSD 5%). Lowest calibrated levels (LCLs) were 0.02 mg/kg for aldicarb
      and aldicarb sulphone and 0.04 mg/kg for aldicarb sulphoxide. At the recommended
      preharvest interval (PHI) of 120 days no detectable residues of any compound,
      including the parent compound, were found in and of the samples analysed. In
      mature fruits (PHI of 88 days) detectable residues at the LCL for aldicarb
      sulphoxide and 0.03 or 0.04 mg/kg for aldicarb sulphone were found in only three
      of the 18 samples analYsed. In immature fruits detectable residues of aldicarb
      sulphoxide at concentrations ranging between 0.04 (LCL) and 0.51 mg/kg were
      detected in 70 out of 88 samples analysed, while residues of aldicarb sulphone at
      concentrations 0.02 (LCL) to 0.8 mg/kg were detected in 73 out of 88 samples.
      Indicative variability factors for sulphoxide and sulphone were estimated for
      immature fruits.

PMID- 11569770
TI  - Investigation of the herbicide glyphosate and the plant growth regulators
      chlormequat and mepiquat in cereals produced in Denmark.
AB  - An LC-MS/MS method for analysing glyphosate and aminomethylphosphonic acid (AMPA)
      in cereals was developed. The method is based on extraction with water and
      detection of the ions from the fragmentation m/z 170-->88 (glyphosate) and m/z
      112-->30 (AMPA), using electrospray interface in the positive mode. Investigation
      from the harvests of 1998 and 1999 showed residues of glyphosate and/or its
      degradation product AMPA in more than half of the cereal samples produced in
      Denmark. The average concentration of glyphosate in 46 samples from the 1999
      harvest was 0.11 mg/kg compared with 0.08 mg/kg for the 1998 harvest (n = 49).
      Thus, the figures were well below the maximum residue limit (MRL) and no
      violations were observed. The plant growth regulators chlormequat and/or mepiquat
      were investigated in cereals from the Danish harvest of 1999 where 83% of the
      samples contained chlormequat (n = 46) compared with 87% of the samples from the
      1997 harvest (n = 52). The average concentration of chlormequat in 1999 was 0.32
      mg/kg compared with 0.23 mg/kg in 1997. At 2.9 mg/kg, one sample of wheat bran
      was exceeding the MRL of 2 mg/kg for wheat. The intakes of the pesticides through
      the diet of cereals were estimated to comprise 0.04% of the acceptable daily
      intake (ADI) for glyphosate and 1% of the ADI for chlormequat for an adult Dane.

PMID- 11569771
TI  - Results from the monitoring of pesticide residues in fruit and vegetables on the
      Danish market, 1998-99.
AB  - The objective of the Danish pesticide monitoring programme for fruit and
      vegetables was to check for compliance with the maximum residue levels in foods
      and to monitor the residue levels to assess the pesticide exposure of the Danish
      population. Sampling plans were designed based on previous findings and on food
      consumption data. Approximately 60% of the samples were selected on the basis of
      positive findings in samples from the previous 5 years. The remaining samples
      reflected the pattern of food consumption in Denmark. In addition, a rolling
      programme is maintained for commodities with a low consumption and no detected
      residues. Within each commodity, the sampling was randon. Samples (n = 4150) of
      mainly fresh, conventionally grown fruit and vegetables were taken throughout the
      chain of suppliers including food-processing companies. Of the samples, 300 were
      frozen products and 2% were organically grown. Of the samples, 35% were of Danish
      origin, with 65% originating from other countries. Three accredited laboratories
      performed analyses of the samples using capillary gas chromatography, liquid
      chromatography and spectrophotometric methods. Results were registered online
      into a central database. Residues were found in 54% of the samples of fruit but
      only in 13% of the vegetables. Residues above the MRL were found in 4% of all
      samples of fruit and in 1% of vegetables.

PMID- 11569772
TI  - Estimation of dietary intake of pesticide residues by the Italian population
      during 1997.
AB  - In 1997 the Italian monitoring programme for pesticide residues in food comprised
      7951 samples of 152 different foods for which a total of 275 pesticides were
      analysed. For 90 pesticides, the National Estimated Daily Intakes (NEDIs) were
      calculated by using the 90th percentile value and the food consumption data for
      the general Italian population. The calculated NEDIs were found to represent only
      a small portion of the respective Acceptable Daily Intake (ADI).

PMID- 11569773
TI  - Is it really duct carcinoma in situ?

PMID- 11569774
TI  - Limitations in controlling risk for recurrence after curative surgery for
      advanced gastric cancer are now well-explained by molecular-based mechanisms.

PMID- 11569775
TI  - Laparoscopic staging for gastric cancer.

PMID- 11569776
TI  - The role of pretherapeutic laparoscopy in the selection of treatment for patients
      with gastric carcinoma: a proposal for a laparoscopic staging system.
AB  - BACKGROUND: A pretherapeutic staging system to design nonoperative or neoadjuvant
      treatments in gastric cancer is required. In this study, a simple staging system
      based on laparoscopic findings to define a treatment algorithm was developed.
      METHODS: A retrospective cohort study was conducted of 151 patients allocated
      into four stages based on laparoscopic findings. The depth of tumor invasion and
      the presence of metastasis based on laparoscopic findings were used to construct
      these stages. Laparoscopic findings were compared with histopathology. RESULTS:
      An excellent agreement of the laparoscopy-defined depth of invasion and the
      surgical pathology standard was found (weighted kappa 0.85). The likelihood
      ratios for a positive and negative laparoscopic diagnosis of metastasis were 40.4
      and 0.015, respectively (98.5% sensitivity, 97.6% specificity). Those for
      positive and negative diagnosis of resectability were 2.6 and 0.03, respectively
      (98.4% sensitivity, 62% specificity). The laparoscopic stages presented
      significant prognostic value. Two-year survival was 93%, 69%, 60%, and 17%,
      respectively. Surgical resection was possible in 100%, 100%, 49%, and 12%,
      respectively. CONCLUSIONS: The proposed laparoscopic staging system is a simple
      and reproducibLe way for selection of a suitable therapy. It allows for adequate
      stratification of the main risk factors in the setting of clinical trials
      evaluating preoperative treatments.

PMID- 11569777
TI  - Outcome of palliative operations for malignant bowel obstruction in patients with
      peritoneal carcinomatosis from nongynecological cancer.
AB  - BACKGROUND: Malignant bowel obstruction (MBO) secondary to peritoneal
      carcinomatosis carries a grave prognosis. We evaluated clinicopathologic factors
      that predict outcomes after palliative operations for MBO. METHODS: Data on
      patients undergoing laparotomy for palliation of gastrointestinal MBO at City of
      Hope between 1995 and 2000 were retrospectively collected. Successful palliation
      was defined as the ability to tolerate solid food (TSF). RESULTS: Sixty-three
      patients underwent operative treatment. In 20 patients, MBO was the first
      presentation of disease; for others, the median disease-free interval was 15
      months. The complication rate was 44%, and postoperative mortality was 15%. The
      median length of stay was 12 days. Twenty-nine patients (45%) were discharged
      from the hospital on a regular diet; 22 (76%) continued to eat until their last
      follow-up. Median survival was 90 days. Univariate factors for longer survival
      were TSF on discharge, colorectal primary, and nonmetastatic status at first
      diagnosis. Patients with ascites and whose cancer first presented with MBO had an
      inferior survival. Noncolorectal primary remained a multivariate predictor for
      decreased survival. TSF was predicted by the absence of ascites, an obstruction
      not involving the small bowel, and a preoperative albumin of >3.0 mg/dl. Multiple
      logistic regression analysis yielded presence of ascites and small-bowel
      obstruction as predictors of inability to TSF. CONCLUSIONS: Only one third of
      patients with MBO from peritoneal carcinomatosis will have prolonged
      postoperative palliation with significant, but acceptable, treatment-related
      morbidity. TSF at discharge is a useful predictor of continued palliation for
      most patients. Patients with colorectal cancer may have superior survival outcome
      and better palliation; others are at risk for poor outcomes, especially in the
      presence of ascites and MBO of small bowel. In these patients, highly selective
      use of laparotomy is recommended.

PMID- 11569778
TI  - The search for level I evidence in solid-tumor oncology.
AB  - BACKGROUND: We have developed a method to identify, filter, review, and
      distribute the published level I evidence for solid tumor oncology. METHODS: A
      standardized MEDLINE search identified prospective randomized controlled trials
      (PRCTs) in solid tumor oncology. Only PRCTs with therapeutic end points were
      included. All references were reviewed by a surgical oncology fellow in
      consultation with experts in the field. The full citations were imported into a
      comprehensive database. Data on statistical methods according to the Consolidated
      Standard of Reporting Trials statement were tabulated along with reviewer's
      comments. A designation of Ia was given to articles that were well designed and
      significant contributions to their field. The database powers a dynamic, easily
      searchable Web site on our intranet and is available in personal digital
      assistant (PDA) format. RESULTS: By using standard search criteria, only .03% of
      the 11 million articles listed in MEDLINE are PRCTs concerning therapy for solid
      organ malignancies. Approximately 14% of reviewed articles were given a
      designation of Ia. Having comprehensive data readily available with intranet
      access or PDAs during conferences enhances their educational value and
      specificity. CONCLUSIONS: We have developed an exciting tool that uses a highly
      trained filter to screen and record the medical data available to the clinician.
      This information has been made available and portable by using the Internet and
      PDAs.

PMID- 11569779
TI  - Surgical resection is necessary to maximize tumor control in function-preserving,
      aggressive chemoradiation protocols for advanced squamous cancer of the head and
      neck (stage III and IV).
AB  - BACKGROUND: The role of surgery in aggressive chemoradiation protocols for
      advanced head and neck cancer has been questioned because of the quoted high
      clinical response rates in many series. METHODS: The role of surgical resection
      was examined in an aggressive neoadjuvant protocol of weekly paclitaxel,
      carboplatin, and radiation for stage III and IV with completion of radiation to
      72 Gy if biopsy at the primary site was negative after administration of 45 Gy.
      Of 43 patients enrolled, 38 completed the protocol. The clinical response was
      100% (including 18 complete and 20 partial responses). RESULTS: The complete
      pathologic response (negative primary site biopsy at 45 Gy) was 25 of 38 (66%).
      Of patients who presented with N1 to N3 nodes, neck dissection revealed residual
      nodal metastases in 22%. Surgical resection of the primary site was required in
      13 patients, including 5 with larynx cancer and 2 with base of tongue cancers.
      Four patients had resection with reconstruction for advanced mandible floor of
      mouth cancer, and one had resection of nasal-maxillary cancer. Functional
      resection was performed in 9 of 12 patients. The median progression free and
      overall survival was 64% and 68%, respectively, at median follow-up of 50 months.
      Nine patients developed recurrence (three local and six distant). There were no
      failures in the neck. Salvage surgery was performed in one patient with local and
      one with distant disease. CONCLUSIONS: Surgical resection is an essential
      component of aggressive chemoradiation protocols to ensure tumor control at the
      primary site and in the neck.

PMID- 11569780
TI  - Radiofrequency ablation for eradication of renal tumor in a rabbit model by using
      a cooled-tip electrode technique.
AB  - BACKGROUND: Radiofrequency ablation (RFA) has emerged as a potential alternative
      for surgery in clinical oncology. This animal experiment was conducted to
      evaluate the feasibility of RFA in the treatment of renal tumor. METHODS:
      Eighteen rabbits with renal implantation of VX2 tumors were divided into two
      groups. Group A (n = 12) was treated with RFA by using a cooled-tip RF system at
      30 W for 80 to 180 seconds. Group B (n = 6) received a sham operation. The
      therapeutic efficacy was evaluated by survival rate, magnetic resonance imaging
      (MRI), and histology. RESULTS: All animals in group B died within 3 months after
      tumor implantation. Total tumor eradication was achieved in 10 of 12 rabbits
      (83.3%) in group A, of which 5 rabbits survived longer than 6 months (absolute
      eradication) and another 5 rabbits were found free of viable tumor when killed
      (relative eradication). Two rabbits experienced local tumor relapse, lung
      metastasis, or both. Six-month survival rate of RFA-treated rabbits was
      significantly higher (P < .01) than that of control rabbits. The typical MRI
      appearances of the acute RFA lesion consisted of five characteristic concentric
      zones, which corresponded to central needle track (zone A), tumor coagulation
      (zone B), renal tissue coagulation (zone C), peripheral hemorrhage (zone D), and
      inflammatory layer (zone E) on histology. CONCLUSIONS: RFA may become a promising
      therapy for the treatment of renal tumor. MRI is a useful modality for assessment
      of renal tumor ablation.

PMID- 11569781
TI  - Does complete resection of melanoma metastatic to solid intra-abdominal organs
      improve survival?
AB  - BACKGROUND: Patients with distant melanoma metastases have median survivals of 4
      to 8 months. Previous studies have demonstrated improved survival after complete
      resection of pulmonary and hollow viscus gastrointestinal metastases. We
      hypothesized that patients with metastatic disease to intra-abdominal solid
      organs might also benefit from complete surgical resection. METHODS: A
      prospectively acquired database identified patients treated for melanoma
      metastatic to the liver, pancreas, spleen, adrenal glands, or a combination of
      these from 1971 to 2000. The primary intervention was complete or incomplete
      surgical resection of intra-abdominal solid-organ metastases, and the main
      outcome measure was postoperative overall survival (OS). Disease-free survival
      (DFS) was a secondary outcome measure. RESULTS: Sixty patients underwent
      adrenalectomy, hepatectomy, splenectomy, or pancreatectomy. Median OS was
      significantly improved after complete versus incomplete resections, but median OS
      after complete resection was not significantly different for single-site versus
      synchronous multisite metastases. The 5-year survival in the group after complete
      resection was 24%, whereas in the incomplete resection group, there were no 5
      year survivors. Median DFS after complete resection was 15 months. Of note, the 2
      year DFS after complete resection was 53% for synchronous multi-site metastases
      versus 26% for single-site metastases. CONCLUSIONS: In highly selected patients
      with melanoma metastatic to intra-abdominal solid organs, aggressive attempts at
      complete surgical resection may improve OS. It is important that the number of
      metastatic sites does not seem to affect the OS after complete resection.

PMID- 11569782
TI  - Prolonged survival after extracranial metastasectomy from synchronous resectable
      lung cancer.
AB  - BACKGROUND: Combined resection of solitary synchronous brain metastases and non
      small-cell lung cancer has been shown to be successful. Thus, we proposed
      combining the surgery of solitary, extracranial metastases, and resectable lung
      cancer. METHODS: Between March 1987 and December 1994, surgery was performed on
      nine patients with non-small-cell lung cancer with synchronous, solitary,
      extracranial, or distant metastasis: adrenal (n = 5), cutaneous (n = 2), axillary
      lymph node (n = 1) and kidney (n = 1). Criteria for operating on these patients
      included: primary tumor that was locally resectable in a radical manner, non
      small-cell histology, no preoperative evidence of N2 disease, complete resection
      of histologically proven metastasis, and absence of other metastases found with
      computed tomography or bone scan. RESULTS: Resection of the primary tumor and
      solitary metastases was achieved in all patients. Primary tumor was always
      resected by lobectomy. No mortality or major morbidity was reported. Five-year
      survival rate was 55.6%. Five patients who had adrenal (n = 3), or skin (n = 1),
      or axillary (n = 1) metastases, survived more than 5 years. All N2 patients (n =
      2) died. CONCLUSIONS: The presence of solitary, distant metastasis should not be
      considered, per se, a factor for denying surgery for locally resectable, non
      small-cell lung cancer. Unexpected, prolonged survival was demonstrated in our
      limited series.

PMID- 11569783
TI  - Lysozyme expression by breast carcinomas, correlation with clinicopathologic
      parameters, and prognostic significance.
AB  - BACKGROUND: Here we evaluate the expression and prognostic value of lysozyme, a
      milk protein that is also synthesized by a significant percentage of breast
      carcinomas, in women with breast cancer. METHODS: Lysozyme expression was
      examined by immunohistochemical methods in a series of 177 breast cancer tissue
      sections. Staining was quantified by using the HSCORE system, which considers
      both the intensity and the percentage of cells staining at each intensity. The
      prognostic value of lysozyme was retrospectively evaluated by multivariate
      analysis that took into account conventional prognostic factors. RESULTS: A total
      of 126 of 177 carcinomas (69.4%) stained positive for this protein, but there
      were clear differences among them with regard to the intensity and percentage of
      stained cells. Lysozyme values were higher in well-differentiated and moderately
      differentiated tumors than in poorly differentiated tumors (P < .05). Similarly,
      lysozyme levels were higher in small and node-negative tumors than in large and
      node-positive tumors (P < .05). Moreover, results indicated that low lysozyme
      content predicted shorter relapse-free survival and overall survival (P < .005).
      Separate Cox multivariate analysis in subgroups of patients as defined by node
      status showed that lysozyme expression was an independent prognostic factor able
      to predict both relapse-free survival and overall survival in node-negative
      patients (P < .05). CONCLUSIONS: Tumoral expression of lysozyme is associated
      with lesions of favorable evolution in breast cancer. This milk protein may be a
      new prognostic factor in patients with breast cancer.

PMID- 11569784
TI  - Occult metastases in sentinel nodes of 200 patients with operable breast cancer.
AB  - BACKGROUND: Up to 30% of patients with operable breast cancer and negative
      regional lymph nodes experience disease recurrence within 10 years. Serial
      sectioning and immunohistochemical staining of these nodes have revealed 9% to
      30% occult metastases. METHODS: Sentinel nodes from 200 patients with T1 and T2
      invasive breast carcinoma were step-sectioned at 2- to 3-mm intervals, fixed in
      10% formalin, and embedded in paraffin. Sections were taken from the face of the
      blocks and stained with hematoxylin and eosin (H&E). The blocks were then cut
      completely, and sections at .25-mm intervals were stained with cytokeratin and
      examined. RESULTS: Tumor metastases were found in 34 patients when the sentinel
      nodes were examined at 2- to 3-mm intervals and in an additional 51 patients when
      the nodes were sectioned in their entirety at .25-mm intervals and stained with
      cytokeratin, bringing the total number of patients with metastases to 85. Of the
      51 patients whose metastases were detected by 2- to 3-mm sectioning and
      cytokeratin staining, 27 had isolated tumor cells and 24 had clusters of
      innumerable malignant cells, all of which were visualized and confirmed by H&E
      staining of the adjacent sections. CONCLUSIONS: Histologic examination of
      sentinel nodes of patients with invasive breast cancer sectioned at 2- to 3-mm
      intervals and stained with H&E significantly underestimates nodal metastases.
      Sectioning of the entire sentinel nodes at .25-mm intervals and staining with
      cytokeratin detects metastases as either isolated cells or as clusters.

PMID- 11569785
TI  - Localization of the sentinel node in breast cancer: identical results with same
      day and day-before isotope injection.
AB  - BACKGROUND: Although the technique of sentinel lymph node (SLN) biopsy in breast
      cancer is not fully standardized, an increasing number of centers map the SLN by
      using radioisotope supplemented by blue dye, and most have injected isotope on
      the day of surgery. Here we directly compare the results of same-day and day
      before isotope injection in a large series of breast cancer patients having SLN
      biopsy with our mature technique. METHODS: Starting with our 961st SLN procedure
      for breast cancer, 1320 consecutive patients had SLN biopsy after the injection
      of unfiltered 99mTc-labeled sulfur colloid given as a single-site, low-volume
      (0.05 ml) intradermal injection: 933 on the day of surgery (1-day protocol) and
      387 on the day before (2-day protocol). All had intraparenchymal injection of
      blue dye. RESULTS: The two groups were comparable in age, tumor location,
      histopathologic characteristics, and number of SLNs identified. LSG taken at 2
      hours in the 2-day protocol was positive more often than LSG performed at 30
      minutes in the 1-day protocol, and nonaxillary sites of lymphatic drainage were
      seen in <1% of each group. Absolute isotope counts and the ratio of SLN to
      axillary background counts were similar. Isotope localization of the SLN
      succeeded in a comparable fraction of patients, as did SLN identification
      overall. CONCLUSIONS: The results of SLN mapping with same-day and day-before
      injection of radioisotope are virtually identical. The logistical advantages of
      day-before injection do not compromise the success of the procedure.

PMID- 11569786
TI  - A review of reproductive strategies in cephalopods.
AB  - Cephalopod reproductive strategies are reviewed in order to clarify their
      current, confusing status. Based on the type of ovulation, spawning pattern and
      growth between egg batches or spawning periods, five comprehensive and flexible
      cephalopod reproductive strategies are defined. Accordingly, with these three
      factors the following classification is proposed. (a) Spawning once (formerly
      semelparity) consisting of simultaneous terminal spawning, with synchronous
      ovulation, monocyclic spawning and absence of growth between egg batches. (b)
      Spawning more than once (formerly iteroparity) including: (i) polycyclic spawning
      with egg-laying occurring in separate batches during the spawning season and
      growth occurring between production of egg batches and spawning seasons; (ii)
      multiple spawning, with group-synchronous ovulation, monocyclic spawning and
      growth between egg batches; (iii) intermittent terminal spawning, with group
      synchronous ovulation, monocyclic spawning and no growth between egg batches;
      (iv) continuous spawning, with asynchronous ovulation, monocyclic spawning and
      growth between egg batches. Examples of species exhibiting each of these
      reproductive strategies are given. The large amount of inter-species variation in
      several life-history traits related to reproductive events is discussed.

PMID- 11569787
TI  - The evolution of male mate choice in insects: a synthesis of ideas and evidence.
AB  - Mate choice by males has been recognized at least since Darwin's time, but its
      phylogenetic distribution and effect on the evolution of female phenotypes remain
      poorly known. Moreover, the relative importance of factors thought to underlie
      the evolution of male mate choice (especially parental investment and mate
      quality variance) is still unresolved. Here I synthesize the empirical evidence
      and theory pertaining to the evolution of male mate choice and sex role reversal
      in insects, and examine the potential for male mating preferences to generate
      sexual selection on female phenotypes. Although male mate choice has received
      relatively little empirical study, the available evidence suggests that it is
      widespread among insects (and other animals). In addition to 'precopulatory' male
      mate choice, some insects exhibit 'cryptic' male mate choice, varying the amount
      of resources allocated to mating on the basis of female mate quality. As
      predicted by theory, the most commonly observed male mating preferences are those
      that tend to maximize a male's expected fertilization success from each mating.
      Such preferences tend to favour female phenotypes associated with high fecundity
      or reduced sperm competition intensity. Among insect species there is wide
      variation in mechanisms used by males to assess female mate quality, some of
      which (e.g. probing, antennating or repeatedly mounting the female) may be
      difficult to distinguish from copulatory courtship. According to theory,
      selection for male choosiness is an increasing function of mate quality variance
      and those reproductive costs that reduce, with each mating, the number of
      subsequent matings that a male can perform ('mating investment') Conversely,
      choosiness is constrained by the costs of mate search and assessment, in
      combination with the accuracy of assessment of potential mates and of the
      distribution of mate qualities. Stronger selection for male choosiness may also
      be expected in systems where female fitness increases with each copulation than
      in systems where female fitness peaks at a small number of matings. This
      theoretical framework is consistent with most of the empirical evidence.
      Furthermore, a variety of observed male mating preferences have the potential to
      exert sexual selection on female phenotypes. However, because male insects
      typically choose females based on phenotypic indicators of fecundity such as body
      size, and these are usually amenable to direct visual or tactile assessment, male
      mate choice often tends to reinforce stronger vectors of fecundity or viability
      selection, and seldom results in the evolution of female display traits. Research
      on orthopterans has shown that complete sex role reversal (i.e. males choosy,
      females competitive) can occur when male parental investment limits female
      fecundity and reduces the potential rate of reproduction of males sufficiently to
      produce a female-biased operational sex ratio. By contrast, many systems
      exhibiting partial sex role reversal (i.e. males choosy and competitive) are not
      associated with elevated levels of male parental investment, reduced male
      reproductive rates, or reduced male bias in the operational sex ratio. Instead,
      large female mate quality variance resulting from factors such as strong last
      male sperm precedence or large variance in female fecundity may select for both
      male choosiness and competitiveness in such systems. Thus, partial and complete
      sex role reversal do not merely represent different points along a continuum of
      increasing male parental investment, but may evolve via different evolutionary
      pathways.

PMID- 11569788
TI  - The evolution of intelligence: adaptive specializations versus general process.
AB  - Darwin argued that between-species differences in intelligence were differences
      of degree, not of kind. The contemporary ecological approach to animal cognition
      argues that animals have evolved species-specific and problem-specific processes
      to solve problems associated with their particular ecological niches: thus
      different species use different processes, and within a species, different
      processes are used to tackle problems involving different inputs. This approach
      contrasts both with Darwin's view and with the general process view, according to
      which the same central processes of learning and memory are used across an
      extensive range of problems involving very different inputs. We review evidence
      relevant to the claim that the learning and memory performance of non-human
      animals varies according to the nature of the stimuli involved. We first discuss
      the resource distribution hypothesis, olfactory learning-set formation, and the
      'biological constraints' literature, but find no convincing support from these
      topics for the ecological account of cognition. We then discuss the claim that
      the performance of birds in spatial tasks of learning and memory is superior in
      species that depend heavily upon stored food compared to species that either show
      less dependence upon stored food or do not store food. If it could be shown that
      storing species enjoy a superiority specifically in spatial (and not non-spatial)
      tasks, this would argue that spatial tasks are indeed solved using different
      processes from those used in non-spatial tasks. Our review of this literature
      does not find a consistent superiority of storing over non-storing birds in
      spatial tasks, and, in particular, no evidence of enhanced superiority of storing
      species when the task demands are increased, by, for example, increasing the
      number of items to be recalled or the duration of the retention period. We
      discuss also the observation that the hippocampus of storing birds is larger than
      that of non-storing birds, and find evidence contrary to the view that
      hippocampal enlargement is associated with enhanced spatial memory; we are,
      however, unable to suggest a convincing alternative explanation for hippocampal
      enlargement. The failure to find solid support for the ecological view supports
      the view that there are no qualitative differences in cognition between animal
      species in the processes of learning and memory. We also argue that our review
      supports our contention that speculation about the phylogenetic development and
      function of behavioural processes does not provide a solid basis for gaining
      insight into the nature of those processes. We end by confessing to a belief in
      one major qualitative difference in cognition in animals: we believe that humans
      alone are capable of acquiring language, and that it is this capacity that
      divides our intelligence so sharply from non-human intelligence.

PMID- 11569789
TI  - Costs of sexual traits: a mismatch between theoretical considerations and
      empirical evidence.
AB  - Costs of sexual traits are of central importance to the theory of sexual
      selection. To qualify as a cost in line with theoretical models, empirical
      studies must demonstrate that sexual traits cause negative effects on one
      component of fitness of the trait bearer. Moreover, it must be demonstrated that
      the costs are differential such that negative effects on fitness are more severe
      for individuals in poor condition than for individuals in good condition.
      However, in the current literature, there is confusion over what qualifies as a
      cost, and costs are often anticipated based on findings of increased expenditure.
      Consequently, it seems that the generally accepted notion that sexual traits are
      costly is in fact based almost exclusively on indirect evidence and that direct
      empirical evidence is very scarce.

PMID- 11569790
TI  - Life in the puddle: behavioural and life-cycle adaptations in the Diptera of
      tropical rain pools.
AB  - Puddles of rain water on the surfaces of rock exposures are a little known but
      very common habitat for freshwater-dwelling animals. In Africa, these are
      inhabited by the larvae of two taxa of fly unique to these pools. One of these
      includes species able to survive dry periods in situ; the other includes species
      that must reach adulthood and migrate to survive periods when the pool is dry.
      Hence, the opportunity exists for a comparative study of adaptation among these
      species. Since puddles are small, our principal method in the study of adaptation
      has been the experimental manipulation of puddles and their faunas in the wild.
      Using this method we were able to identify the spatial consistency of pools and
      their unpredictable duration during the rainy season as the main selective
      pressure shaping adaptation. Adaptations include diapause and adaptive adjustment
      of the life cycle. It is the second of these that provides the focus of our
      interest here.

PMID- 11569791
TI  - Seeing in the dark: molecular approaches to the study of bat populations.
AB  - Whilst the use of molecular genetic techniques is widespread in the fields of
      population and evolutionary biology, their application within the mammalian order
      Chiroptera neither reflects the species richness nor the ecological and
      behavioural diversity of the order. This is despite the fact that the Chiroptera
      are problematic to study using more direct observational techniques. Here, we
      standardize and synthesise the current data, assess the contribution of molecular
      research to the study of bat species and highlight the importance of its
      continued and expanded use. At an inter-population level, molecular studies have
      demonstrated a great diversity of population genetic structure within the order.
      Among populations of migratory species, genetic structure appears universally
      low, and hence seasonal movement is likely to be the prevailing influence.
      However, for sedentary species an array of factors including dispersal ability,
      extrinsic barriers to gene flow and historical events may determine the extent of
      genetic partitioning among populations. Intrinsic factors such as wing morphology
      or roost requirements may also influence population genetic structure in
      sedentary bat species, a proposal which requires further research. Molecular
      studies have also made important contributions towards an understanding of social
      organisation in bats. Evidence indicates that in many polygynous species male
      mating success does not translate directly into reproductive success, perhaps as
      a result of multiple mating by females. Estimates of relatedness within and
      genetic structure among colonies are, in general, very low; a finding which has
      important implications regarding theories concerning the formation and
      persistence of bat social groups. Molecular studies have provided new and
      important insights into the ecology of bats, and have opened up exciting and
      previously unexplored avenues of research. The data from these studies suggest
      not only a predictive framework for future studies, but also the use of genetic
      data in the management and conservation of bat species.

PMID- 11569792
TI  - Did dinosaurs invent flowers? Dinosaur-angiosperm coevolution revisited.
AB  - Angiosperms first appeared in northern Gondwana during the Early Cretaceous,
      approximately 135 million years ago. Several authors have hypothesised that the
      origin of angiosperms, and the tempo and pattern of their subsequent radiation,
      was mediated by changes in the browsing behaviour of large herbivorous dinosaurs
      (sauropods and ornithischians). Moreover, the taxonomic and ecological radiation
      of angiosperms has been associated with the evolution of complex jaw mechanisms
      among ornithischian dinosaurs. Here, we review critically the evidence for
      dinosaur-angiosperm interactions during the Cretaceous Period, providing explicit
      spatiotemporal comparisons between evolutionary and palaeoecological events in
      both the dinosaur and angiosperm fossil records and an assessment of the direct
      and indirect evidence for dinosaur diets. We conclude that there are no strong
      spatiotemporal correlations in support of the hypothesis that dinosaurs were
      causative agents in the origin of angiosperms; however, dinosaur-angiosperm
      interactions in the Late Cretaceous may have resulted in some coevolutionary
      interactions, although direct evidence of such interactions is scanty at present.
      It is likely that other animal groups (insects, arboreal mammals) had a greater
      impact on angiosperm diversity during the Cretaceous than herbivorous dinosaurs.
      Elevated levels of atmospheric CO2 might have played a critical role in the
      initial stages of the angiosperm radiation.

PMID- 11569793
TI  - Virtual 2-D gel electrophoresis: visualization and analysis of the E. coli
      proteome by mass spectrometry.
AB  - Mass spectrometric surface analysis of isoelectric focusing gels provides an
      ultrasensitive approach to proteome analysis. This "virtual 2-D gel" approach, in
      which mass spectrometry is substituted for the size-based separation of SDS-PAGE,
      provides advantages in mass resolution and accuracy over classical 2-D gels and
      can be readily automated. Protein identities can be postulated from molecular
      mass (+/-0.1-0.2% for proteins of <50 kDa in size) and pI (+/-0.3 pH unit) and
      confirmed by MALDI in-source decay of the intact protein (providing sequence
      spanning up to 43 residues) or by peptide mass mapping following gel-wide
      chemical cleavage. Additionally, posttranslational modifications such as fatty
      acid acylation can be detected by the mass-resolved heterogeneity of component
      hydrocarbon chains. Sensitivity was evaluated by comparing the number of proteins
      detected by this method to equivalently loaded silver-stained 2-D gels. In the
      5.7-6.0 pH range, E. coli is predicted to contain 435 proteins; virtual 2-D gels
      found 250 proteins ranging from >2 to <120 kDa in size present at levels to tens
      of femtomoles, as compared to the 100 proteins found by silver-staining 2-D gels.
      Extrapolating this result to the total theoretical proteome suggests that this
      technology is capable of detecting over 2500 E. coli proteins.

PMID- 11569795
TI  - Microchip injection and separation anomalies due to pressure effects.
AB  - While performing routine electroosmotically driven CE separations on microfluidic
      chips, we have observed peak shape, migration time, and baseline drift anomalies.
      Pressure-driven backflow (opposing electroosmotic flow (EOF)) has been observed
      and characterized, and meniscus surface tension (Laplace pressure) is cited as
      the likely cause. However, there are a number of interdependent factors that
      affect bulk flow in a microchip environment, including evaporation, buffer
      depletion due to hydrolysis, EOF pumping, siphoning, viscosity changes due to
      Joule heating, and Laplace pressure. Given the complexity of such a system,
      pressure effects were isolated from EOF, and to some extent, siphoning effects
      were isolated from suspected meniscus effects. Pressure flow observed in the
      absence of an applied field ranged from 0.4 to 0.8 mm/s, which was on the order
      of the EOF generated experimentally, 0.6 mm/s at a field of 150 V/cm, and was
      some 10-20 times larger than what would be predicted merely from a difference in
      liquid levels (siphoning). Furthermore, experiments were performed without an
      electric field and with the chip tilted so that meniscus flow ran "uphill"
      against a siphoning backflow and showed siphoning flow to have a negligible
      effect upon meniscus flow under the microchip conditions studied. These findings
      are relevant to the profusion of microfluidic and array-based technology that
      also use microliter liquid volumes in like-sized reservoirs with similar menisci.

PMID- 11569794
TI  - Metathesis-based monoliths: influence of polymerization conditions on the
      separation of biomolecules.
AB  - Monolithic materials were prepared by transition metal-catalyzed ring-opening
      metathesis copolymerization of norborn-2-ene and 1,4,4a,5,8,8a-hexahydro-1,4,5,8
      exo,endo-dimethanonaphthalene within the confines of surface-derivatized
      borosilicate columns in the presence of the porogenic solvents toluene and 2
      propanol using Cl2(PCy3)2Ru(=CHPh) (1) as initiator. Relevant physicochemical
      data of the porous structure (specific surface area (sigma), pore volume (Vp),
      volume fraction of pores (epsilon(p)), and intermicroglobule volume (epsilon(z)))
      of the monolithic columns were determined by inverse size exclusion
      chromatography in tetrahydrofuran. Mean particle diameters were determined via
      electron microscopy. The influence of variations in polymerization conditions in
      terms of stoichiometry of the monomers and porogenic solvents on the
      chromatographic separation of the oligodeoxynucleotides dT12-dT18 and eight model
      proteins (ribonuclease A, insulin, cytochrome c, lysocyme, alpha-lactalbumin,
      alpha-chymotrypsinogen, beta-lactoglobulin B, catalase) were studied. Also, the
      role of additional phosphine on the entire polymerization setup and the
      associated chromatographic separations was elucidated. Relevant chromatographic
      data as well as differences between the separation of oligodeoxynucleotides and
      proteins may directly be attributed to the above-mentioned physicochemical
      properties of the metathesis-based monoliths. Finally, DSC-TGA-MS investigations
      on various monoliths of different composition and age were carried out in order
      to provide information on stability and oxidation behavior.

PMID- 11569796
TI  - An in situ study of metal complexation by an immobilized synthetic biopolymer
      using tapping mode liquid cell atomic force microscopy.
AB  - Near-field scanning optical microscopy and tapping mode, liquid cell atomic force
      microscopy were used to study the conformational changes in simple short-chain
      silica-immobilized biopolymer, poly(L-cysteine) (PLCys), as the polymer was
      exposed to reducing, metal-rich, and acidic environments, respectively, to
      simulate on-line metal preconcentration. In a reducing environment (0.01 M
      dithiothreitol in pH 7.0 ammonium acetate buffer), the PLCys features resembled
      islands on the surface of the glass, 36 +/- 7 nm in height and 251 +/- 60 nm in
      diameter. Upon exposure to metal (Cd2+ buffered at pH 7.0), the PLCys islands
      broke up into smaller metal binding clusters whose features were lower in height,
      22 +/- 5 nm, and diameter, 213 +/- 53 nm. Exposure to 0.01 M HCl used for metal
      stripping resulted in protonation of the polymer chains and further reduction in
      the polymer height to 12 +/- 5 nm. These changes in molecular structure have
      given new insight into the mechanisms involved to achieve strong binding as well
      as rapid, quantitative release of bound metals to flexible short-chain synthetic
      biopolymers.

PMID- 11569797
TI  - Microenviromental investigation of polymer-bound fluorescent chelator by
      fluorescence microscopy and optical spectroscopy.
AB  - 8-Hydroxyquinoline-5-sulfonic acid (HQS) was immobilized onto a strong-base anion
      exchange resin AG MP-1 for the purpose of microenvironment investigation, resin
      characterization, and possibly sensing cadmium. The maximum loading of HQS was
      found to be 0.9340 mmol/g of AG MP-1. A plateau for Cd complex capacity was
      already obtained for 0.5500 mmol of HQS/g of AG MP-1. A minicolumn experiment
      showed an influence of influent Cd concentration on column capacity. IR and Raman
      spectra proved an electrostatic mode for HQS immobilization and Cd complex
      formation. UV spectroscopy showed significant differences between solution and
      solid state for both HQS and Cd complex. A fluorescence microscopy technique was
      used for fluorescence spectral measurement, microdistribution imaging, and study
      of photobleaching of HQS and the HQS-Cd complex in the resin phase. The
      fluorescence of immobilized HQS was found to be red-shifted with regard to the
      solid-state HQS. The microdistribution of uncomplexed and Cd-complexed AG MP-1
      HQS was directly visualized by fluorescence imaging, showing a nonuniform
      distribution. Cadmium complexation modifies the fluorescence emission of
      uncomplexed AG MP-1-HQS, exhibiting an increased and red-shifted emission.
      Significant photobleaching of the fluorescence from the Cd complex was recorded,
      indicating the occurrence of photochemical reactions within the microenvironment
      of the resin phase.

PMID- 11569798
TI  - High-precision continuous-flow measurement of delta13C and deltaD of atmospheric
      CH4.
AB  - We describe our development of a CH4 preconcentration system for use with
      continuous-flow gas chromatograph combustion isotope ratio mass spectrometry
      (GC/C/IRMS). Precision of measurement of delta13C-CH4 is 0.05/1000 (1sigma) on
      multiple 60-mL aliquots of the same ambient air sample. The same front-end on
      line CH4 preconcentration system allows us to measure deltaD of CH4 by gas
      chromatography IRMS when the combustion furnace is replaced with a pyrolysis oven
      (GC/P/IRMS). Precision of measurement for deltaD-CH4 is 1.5/1000 (1sigma) using
      120 mL of ambient air based on multiple aliquots of the same air sample. These
      are the first reported measurements of atmospheric CH4 using GC/P/IRMS
      methodology. Each isotope analysis can be made much more rapidly (30-40 min) than
      they could using off-line combustion of an air sample (1-6 h) followed by
      conventional dual-inlet IRMS measurements (12-20 min), while requiring much less
      total volume and retaining a comparable level of precision and accuracy. To
      illustrate the capabilities of our preconcentration GC/C/IRMS system, we compare
      the results of measurement of 24 background air samples made using both GC/C/IRMS
      and conventional vacuum line/dual-inlet IRMS methodology. The air samples were
      collected on a shipboard air sampling transect made across the Pacific Ocean in
      July 2000 and are part of an ongoing atmospheric CH4 research program. The
      average difference between the two methods of IRMS analyses on these 24 samples
      is 0.01 +/- 0.03/1000 (95% confidence interval) for delta3C-CH4. These are the
      first measurements to be reported of air samples directly intercompared for
      delta13C-CH4 using both GC/C/IRMS and dual-inlet IRMS measurement methodology.
      Measurement of deltaD-CH4 of these air samples is also presented as an
      illustration of the ability of this system to resolve small isotopic differences
      in remote air. High-precision measurement of delta13C and deltaD of atmospheric
      CH4 made using our coupled preconcentration GC/IRMS system will greatly improve
      our ability to utilize isotopic data in understanding spatial and temporal
      changes in atmospheric CH4 and the biogeochemistry of its sources and sinks.

PMID- 11569799
TI  - Continuous-flow analysis of dissolved inorganic carbon content in seawater.
AB  - A rapid, continuous-flow determination of total inorganic carbon (TIC) in
      seawater samples is presented. The method runs on an autoanalyzer Traacs 800
      spectrophotometric system and is calibrated versus certified reference materials
      readily available. A typical analysis speed of 45 samples/h can be reached with
      an accuracy of 2-3 microM and a precision of approximately 2.5 microM. The
      analysis requires only a small amount of sample and is thus ideally suited for
      pore water samples and samples taken from cultures where sample volume is at a
      premium. The speed of the analysis makes mapping of oceanic surface water
      characteristics possible. Potential interference of sulfide in anoxic (e.g., pore
      water) samples can be masked by the addition of a hydrogen peroxide step.
      Although the latter is a strong oxidative reagent, no significant effect on TIC
      concentration due to oxidation of (labile) organic matter could be found.

PMID- 11569800
TI  - Temperature measurement in microfluidic systems using a temperature-dependent
      fluorescent dye.
AB  - A technique is described for the measurement of fluid temperatures in
      microfluidic systems based on temperature-dependent fluorescence. The technique
      is easy to implement with a standard fluorescence microscope and CCD camera. In
      addition, the method can be used to measure fluid temperatures with micrometer
      spatial resolution and millisecond time resolution. The efficacy of the method is
      demonstrated by measuring temperature distributions resulting from Joule heating
      in a variety of microfluidic circuits that are electrokinetically pumped. With
      the equipment used for these measurements, fluid temperatures ranging from room
      temperature to 90 degrees C were measured with a precision ranging from 0.03 to
      3.5 degrees C-dependent on the amount of signal averaging done. The spatial and
      temporal resolutions achieved were 1 microm and 33 ms, respectively.

PMID- 11569801
TI  - A real-time ratiometric method for the determination of molecular oxygen inside
      living cells using sol-gel-based spherical optical nanosensors with applications
      to rat C6 glioma.
AB  - The first sol-gel-based, ratiometric, optical nanosensors, or sol-gel probes
      encapsulated by biologically localized embedding (PEBBLEs), are made and
      demonstrated here to enable reliable, real-time measurements of subcellular
      molecular oxygen. Sensors were made using a modified Stober method, with
      poly(ethylene glycol) as a steric stabilizer. The radii of these spherical PEBBLE
      sensors range from about 50 to 300 nm. These sensors incorporate an oxygen
      sensitive fluorescent indicator, Ru(II)-tris(4,7-diphenyl-1,10-phenanthroline)
      chloride ([Ru(dpp)3]2+), and an oxygen-insensitive fluorescent dye, Oregon Green
      488-dextran, as a reference for the purpose of ratiometric intensity
      measurements. The PEBBLE sensors have excellent reversibility, dynamic range, and
      stability to leaching and photobleaching. The small size and inert matrix of
      these sensors allow them to be inserted into living cells with minimal physical
      and chemical perturbations to their biological functions. Applications of sol-gel
      PEBBLEs inserted in rat C6 glioma cells for real-time intracellular oxygen
      analysis are demonstrated. Compared to using free dyes for intracellular
      measurements, the PEBBLE matrix protects the fluorescent dyes from interference
      by proteins in cells, enabling reliable in vivo chemical analysis. Conversely,
      the matrix also significantly reduces the toxicity of the indicator and reference
      dyes to the cells, so that a wide variety of dyes can be used in optimal fashion.

PMID- 11569802
TI  - Discrimination of aerobic endospore-forming bacteria via electrospray-lonization
      mass spectrometry of whole cell suspensions.
AB  - Direct injection electrospray ionization mass spectrometry (ESI-MS) without prior
      analyte separation was investigated for the analysis of whole cell suspensions of
      bacteria. Thirty-six strains of aerobic endospore-forming bacteria, consisting of
      six Bacillus species and one Brevibacillus species, were studied

PMID- 11569803
TI  - A bacterial method for the nitrogen isotopic analysis of nitrate in seawater and
      freshwater.
AB  - We report a new method for measurement of the isotopic composition of nitrate
      (NO3-) at the natural-abundance level in both seawater and freshwater. The method
      is based on the isotopic analysis of nitrous oxide (N20) generated from nitrate
      by denitrifying bacteria that lack N2O-reductase activity. The isotopic
      composition of both nitrogen and oxygen from nitrate are accessible in this way.
      In this first of two companion manuscripts, we describe the basic protocol and
      results for the nitrogen isotopes. The precision of the method is better than
      0.2/1000 (1 SD) at concentrations of nitrate down to 1 microM, and the nitrogen
      isotopic differences among various standards and samples are accurately
      reproduced. For samples with 1 microM nitrate or more, the blank of the method is
      less than 10% of the signal size, and various approaches may reduce it further.

PMID- 11569804
TI  - Observation of the iron-sulfur cluster in Escherichia coli biotin synthase by
      nanoflow electrospray mass spectrometry.
AB  - Biotin synthase from Escherichia coli was analyzed by nanoflow electrospray
      ionization mass spectrometry. From solution conditions in which the protein is in
      its native state, a distribution of monomeric, dimeric, and tetrameric species
      was observed. The distribution of these species was sensitive to changes in ionic
      strength: in the positive ion spectrum, biotin synthase at low ionic strength (pH
      7.0-8.5) yielded less than 10% dimer. The masses of the monomeric species were
      consistent with the presence of a [2Fe-2S] cluster with a mass difference of
      175.3 Da from the apomonomer with one disulfide bond. Despite the molecular mass
      of the noncovalent dimer (77 kDa), it was possible to observe a dimeric species
      containing one iron-sulfur cluster in both positive and negative ion spectra.
      Additionally, observation of a series of charge states assigned to the apodimer
      indicated that binding of the iron-sulfur cluster was not required to maintain
      the dimer. Binding of Cu2+ to biotin synthase was also observed; in the presence
      of excess chelating agent, free metals were removed and the iron-sulfur cluster
      remained intact. Evidence for the coordination of the iron-sulfur cluster in
      biotin synthase was obtained in a tandem mass spectrometry experiment. A single
      charge state containing the cluster at m/z 2416.9 was isolated, and collision
      induced dissociation resulted in sequential loss of sulfur and retention of Fe3+.

PMID- 11569805
TI  - A multicapillary inlet jet disruption electrodynamic ion funnel interface for
      improved sensitivity using atmospheric pressure ion sources.
AB  - A new multicapillary inlet and ion funnel interface for electrospray ionization
      mass spectrometry has been developed and demonstrated to achieve higher ion
      transmission efficiency compared to a single-capillary inlet and ion funnel
      interface. Even though the distance between the end of the ESI inlet capillary
      and the exit of the ion funnel (10 cm) is significantly longer than that of the
      conventional interface (typically a few millimeters), a significant part of the
      directed inlet gas flow persists into the first stage of pumping and results in
      an increased gas load to the second chamber. A jet disrupter made of a circular
      metal disk placed on axis in the ion funnel enhanced the dispersion of the
      directed gas flow from a multicapillary inlet and was also found to improve the
      ion transmission. The ion funnel with the jet disrupter demonstrated a 15%
      improvement in ion transmission (compared to that without the jet disrupter) and
      simultaneously reduced the pumping speed required for the first or second stage
      by a factor of 2-3. Compared to the sensitivity with the standard mass
      spectrometer interface (an API 3000, Sciex, Concord, ON, Canada) in MS/MS
      operation using an interface equipped with the jet disrupter and ion funnel, a
      5.3-10.7-fold enhancement in signal was observed for samples with concentrations
      of 100-500 pg/microL and 10.2 to 14.1-fold enhancement for concentrations of 10
      to 50 pg/microL. The decreased enhancement at higher concentrations is attributed
      to space charge effects and detector saturation.

PMID- 11569806
TI  - A capillary-based supersonic jet inlet system for resonance-enhanced laser
      ionization mass spectrometry: principle and first on-line process analytical
      applications.
AB  - A new supersonic jet inlet system for resonance-enhanced multiphoton ionization
      time-of-flight mass spectrometry (REMPI-TOFMS), based on a fused-silica capillary
      with an integral nozzle has been developed. The new jet inlet system generates a
      supersonic molecular beam that originates in the center of the ion source of the
      time-of-flight mass spectrometer. Because of the design of the inlet system, high
      spatial overlap of sample and laser beam (i.e., increased detection sensitivity)
      and excellent jet beam qualities are achieved with good adiabatic cooling
      properties of analyte molecules (i.e., considerably enhanced optical selectivity
      of the REMPI process). Furthermore, the inlet is very robust and chemically inert
      and contains no moving parts. As a result of these properties, the new inlet is
      perfectly suited for field applications of jet-REMPI. A first field application
      of a mobile supersonic jet-REMPI mass spectrometer equipped with the novel inlet
      technique is reported; namely, the concentration of monochlorobenzene, which is
      an indicator for the formation and emission of toxic polychlorinated dibenzo-p
      dioxins/furans, PCDD/F) was measured on-line in the flue gas of a waste
      incineration plant.

PMID- 11569807
TI  - Surface biopassivation of replicated poly(dimethylsiloxane) microfluidic channels
      and application to heterogeneous immunoreaction with on-chip fluorescence
      detection.
AB  - Poly(dimethylsiloxane) (PDMS) appeared recently as a material of choice for rapid
      and accurate replication of polymer-based microfluidic networks. However, due to
      its hydrophobicity, the surface strongly interacts with apolar analytes or
      species containing apolar domains, resulting in significant uncontrolled
      adsorption on channel walls. This contribution describes the application and
      characterization of a PDMS surface treatment that considerably decreases
      adsorption of low and high molecular mass substances to channel walls while
      maintaining a modest cathodic electroosmotic flow. Channels are modified with a
      three-layer biotin-neutravidin sandwich coating, made of biotinylated IgG,
      neutravidin, and biotinylated dextran. By replacing biotinylated dextran with any
      biotinylated reagent, the modified surface can be readily patterned with
      biochemical probes, such as antibodies. Combination of probe immobilization
      chemistry with low nonspecific binding enables affinity binding assays within
      channel networks. The example of an electrokinetic driven, heterogeneous
      immunoreaction for human IgG is described.

PMID- 11569808
TI  - Solid-state NMR characterization of amylose tris(3,5-dimethylphenylcarbamate)
      chiral stationary-phase structure as a function of mobile-phase composition.
AB  - Solid-state NMR (1H/13C CPMAS) was utilized to identify structural differences in
      amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase (Chiralpak AD),
      as a function of mobile-phase composition. Dry Chiralpak AD stationary phase
      displayed an amorphous CPMAS NMR spectrum. However, CPMAS spectra of Chiralpak AD
      flushed with organic mobile phases clearly displayed evidence of solvent
      complexes. Chiralpak AD flushed with nonpolar hexane exhibited solvent complexes
      with minimal structural perturbation. For Chiralpak AD flushed with hexane
      containing alcohol modifiers, however, solvent incorporation caused significant
      difference in conformation distribution as evidenced by increased resolution of
      13C peaks in the CPMAS spectrum of the stationary phase. 2-Propanol modifier
      displayed more efficient displacement of incorporated hexane while forming
      relatively more distinct/ordered solvent complexes with Chiralpak AD in
      comparison to ethanol modifier. Reversed elution order and unusual retention
      behavior on Chiralpak AD as a function of mobile-phase modifier was reported
      earlier. These chromatographic behaviors are believed to be due to different
      alterations of the steric environment of the chiral cavities in the CSP by the
      different mobile-phase modifiers. In addition, on the basis of the chemical shift
      of C-1 carbon on the amylose backbone, it is possible that Chiralpak AD's
      structure is a helix with a number of fold less than six.

PMID- 11569809
TI  - Microfabricated polycarbonate CE devices for DNA analysis.
AB  - The microchip capillary electrophoresis (CE) devices were fabricated in
      polycarbonate (PC) plastic material by compression molding. The molded devices
      were enclosed utilizing thermal bonding to another PC wafer. These thermal bonds
      do not yield up to an applied force equivalent to 150 psi. Aqueous fluid
      transport inside the plastic CE devices was enhanced by UV irradiation treatment
      of the hydrophobic polycarbonate plastic surfaces prior to thermal bonding. In
      comparison to glass microchannels, electroosmotic flow (EOF) in native PC
      channels is low and is independent of buffer pH at pH 7 and 9. UV irradiation of
      PC surfaces increases surface hydrophilicity and increases EOF. CE DNA separation
      was demonstrated in these PC CE devices with good resolution and run-to-run
      reproducibility. The on-chip PCR/CE analysis of a 500-bp region of bacteriophage
      lambda DNA was also demonstrated.

PMID- 11569810
TI  - A data analysis algorithm for programmed field-flow fractionation.
AB  - An algorithm that employs numerical integration for analysis of field-flow
      fractionation (FFF) data is presented. The algorithm utilizes detector response,
      field strength, and channel flow rate data, monitored at discrete time intervals
      during sample elution to generate a distribution of sample components according
      to particle size or molecular weight. The field strength and channel flow rate
      may either be held constant or programmed as functions of time, and it is not
      necessary for these programs to follow specific mathematical functions. If
      experimental conditions are monitored during a run, the algorithm can account for
      any deviation from nominal set conditions. The algorithm also allows calculation
      of fractionating power for the actual conditions as monitored during the run. The
      method provides greatly increased flexibility in the application of the FFF
      family of techniques. It removes the limitations on experimental conditions
      incurred by adherence to analytically available solutions to FFF theory, allowing
      ad hoc variation of field strength and other experimental parameters as necessary
      to increase sensitivity and specificity of the method. An implementation of the
      algorithm is described that is independent of the FFF technique (i.e.,
      independent of field type) and mode of operation. To reduce computation time, it
      uses mathematical techniques to reduce the required number of numerical
      integrations. This is of particular importance when the perturbations to ideal
      FFF theory, such as those due to the effects of hydrodynamic lift forces,
      particle-wall or particle-particle interactions, and secondary relaxation,
      necessitate relatively lengthy numerical calculations.

PMID- 11569811
TI  - Biocolloids with ordered urease multilayer shells as enzymatic reactors.
AB  - The preparation of biocolloids with organized enzyme-containing multilayer shells
      for exploitation as colloidal enzymatic nanoreactors is described. Urease
      multilayers were assembled onto submicrometer-sized polystyrene spheres by the
      sequential adsorption of urease and polyelectrolyte, in a predetermined order,
      utilizing electrostatic interactions for layer growth. The catalytic activity of
      the biocolloids increased proportionally with the number of urease layers
      deposited on the particles, demonstrating that biocolloid particles with tailored
      enzymatic activities can be produced. It was further found that precoating the
      latex spheres with nanoparticles (40-nm silica or 12-nm magnetite) enhanced both
      the stability (with respect to adsorption) and enzymatic activity of the urease
      multilayers. The presence of the magnetite nanoparticle coating also provided a
      magnetic function that allowed the biocolloids to be easily and rapidly separated
      with a permanent magnet. The fabrication of such colloids opens new avenues for
      the application of bioparticles and represents a promising route for the creation
      of complex catalytic particles.

PMID- 11569812
TI  - Determination of radium-226 in aqueous solutions by alpha-spectrometry.
AB  - The new European legislation imposes a lower threshold for radioactivity in
      drinking water. This requires the development of more sensitive and reliable
      analytical methods. This work presents an improved alpha-spectrometric technique
      to determine the radium-226 activity in aqueous solution relying on the radium
      adsorption onto a thin manganese oxide layer followed by alpha-measurement. The
      preparation of the MnO2 deposit has been optimized as well as the radium
      adsorption conditions. Detection threshold and limit of 5 and 10 mBq x L(-1),
      respectively, with a 10% (95% confidence) uncertainty are currently reached. This
      paper reports on the overall technique and on its application to assess the
      radium-226 activity in 28 French mineral waters. In addition, the gross alpha-
      and beta-activities have been evaluated using proportional counting while the
      uranium concentrations were derived from ICPMS.

PMID- 11569813
TI  - Molecular-imprinted, polymer-coated quartz crystal microbalances for the
      detection of terpenes.
AB  - A piezoelectric sensor coated with an artificial biomimetic recognition element
      has been developed for the determination of L-menthol in the liquid phase. A
      highly specific noncovalently imprinted polymer (MIP) was cast in situ on to the
      surface of a gold-coated quartz crystal microbalance (QCM) electrode as a thin
      permeable film. Selective rebinding of the target analyte was observed as a
      frequency shift quantified by piezoelectric microgravimetry with the QCM. The
      detectability of L-menthol was 200 ppb with a response range of 0-1.0 ppm. The
      response of the MIP-QCM to a range of monoterpenes was investigated with the
      sensor binding menthol in favor of analogous compounds. The sensor was able to
      distinguish between the D- and L-enantiomers of menthol owing to the
      enantioselectivity of the imprinted sites. To our knowledge, this is the first
      report describing enantiomeric resolution within an MIP utilizing a single
      monomer-functional moiety interaction. It is envisaged that this technique could
      be employed to determine the concentration of terpenes in the atmosphere.

PMID- 11569814
TI  - Scanning capillary microscopy/mass spectrometry for mapping spatial
      electrochemical activity of electrodes.
AB  - A new technique for microscopic imaging of electrochemically active surfaces is
      introduced. The technique combines concepts of probe microscopy and advances in
      mass spectrometry. The technique is based on a miniature electrochemical flow
      cell scanner. A liquid feed stream containing a redox component is introduced to
      the vicinity of the examined location through the annulus of a coaxial capillary
      set. The incoming reagent interacts with the target location, and the generated
      product stream is transferred through the inner capillary to an electrospray mass
      spectrometer, ESI-MS. Thus, a multicomponent, potential-dependent image of the
      products' distribution versus the location on the electrode is generated. The use
      of the technique is demonstrated by scanning the electrochemical heterogeneity of
      model electrodes.

PMID- 11569815
TI  - Electrochemical biosensor array for the identification of microorganisms based on
      lectin-lipopolysaccharide recognition.
AB  - Rapid identification of bacterial strains remains a well-known problem in applied
      medicine and, for viable pathogens, is an important diagnostic goal. We have
      investigated an electrochemical biosensor array, in which transduction is based
      on respiratory cycle activity measurements, where the microorganism's native
      respiratory chain is interrupted with non-native external oxidants. The selective
      biochemical recognition agents employed in this study are lectins that, once
      immobilized, recognize and bind to cell surface lipopolysaccharides. Porous
      membranes with different surface properties were examined as potential
      immobilization supports for these lectins. Optimizations performed using
      concanavalin A and E. coli JM105 show that immobilization methods involving pre
      activated membranes significantly reduce the time required to create a functional
      lectin layer on the membrane surface. Overall, we found general agreement between
      agglutination test results and the electrochemical assessment of lectin-cell
      binding. Chronocoulometric measurements were made for cells captured on lectin
      modified Immunodyne ABC membranes physically affixed to Pt working electrodes.
      This lectin-based sensor array was exposed to viable cells of gram-negative and
      gram-positive bacteria as well as yeast, and chronocoulometric measurements were
      used to generate a pattern of responses for each organism toward each lectin.
      Principal component analysis was used to classify the chronocoulometric results
      for the different microbial strains. With this new method, six microbial species
      (Baccilus cereus, Staphylococcus aureus, Proteus vulgaris, Escherichia coli,
      Enterobacter aerogenes, Saccharomyces cerevisiae) were readily distinguished.

PMID- 11569816
TI  - Picomolar detection limits with current-polarized Pb2+ ion-selective membranes.
AB  - Minor ion fluxes across ion-selective membranes bias submicromolar activity
      measurements with conventional ion-selective electrodes. When ion fluxes are
      balanced, the lower limit of detection is expected to be dramatically improved.
      As proof of principle, the flux of lead ions across an ETH 5435 ionophore-based
      lead-selective membrane was gradually compensated by applying a few nanoamperes
      of galvanostatic current. When the opposite ion fluxes were matched, and the
      undesirable leaching of primary ions was eliminated, Nernstian response down to 3
      x 10(-12) M was achieved.

PMID- 11569817
TI  - A method for the design and study of enzyme microstructures formed by means of a
      flow-through microdispenser.
AB  - Micrometer-sized enzyme grids were fabricated on gold surfaces using a novel
      method based on a flow-through microdispenser. The method involves dispensing
      very small droplets of enzyme solution (approximately 100 pL) during the
      concomitant relative movement of a gold substrate with respect to the nozzle of a
      microdispenser, resulting in enzyme patterns with a line width of approximately
      100 microm. Different immobilization methods have been evaluated, yielding either
      enzyme monolayers using functionalized self-assembled thiol monolayers for
      covalent binding of the enzyme or enzyme multilayers by cross-linking or
      entrapping the enzymes in a polymer film. The latter immobilization techniques
      allow the formation of coupled multienzyme structures. On the basis of this
      feature, coupled bienzyme (glucose oxidase and catalase) or three-enzyme (alpha
      glucosidase, mutarotase, and glucose oxidase) microstructures consisting of line
      patterns of one enzyme intersecting with the patterned lines of the other
      enzyme(s) were fabricated. By means of scanning electrochemical microscopy (SECM)
      operated in the generator-collector mode, the enzyme microstructures and their
      integrity were visualized using the localized detection of enzymatically
      produced/consumed H2O2. A calibration curve for glucose could be obtained by
      subsequent SECM line scans over a glucose oxidase microstructure for increasing
      glucose concentrations, demonstrating the possibility of obtaining localized
      quantitative data from the prepared microstructures. Possible applications of
      these enzyme microstructures for multianalyte detection and interference
      elimination and for screening of different biosensor configurations are
      highlighted.

PMID- 11569819
TI  - Characterization of silane-modified immobilized gold colloids as a substrate for
      surface-enhanced Raman spectroscopy.
AB  - Immobilized gold colloid particles coated with a C-18 alkylsilane layer have been
      characterized as a substrate for surface-enhanced Raman scattering (SERS) studies
      of adsorption onto hydrophobic surfaces. Atomic force microscopy images, optical
      extinction spectra, and SERS measurements are reported as a function of
      accumulation of gold colloid on glass. As the metal particles become increasingly
      aggregated on the surface, the SERS enhancement increases until the plasmon
      resonance shifts to wavelengths longer than the excitation laser. The gold
      colloid substrates are stable and exhibit reproducible SERS enhancement. When
      octadecyltrimethoxysilane is self-assembled over the gold, the metal surface is
      protected from exposure to solution-phase species, as evidenced by the inhibition
      of chemisorption of a disulfide reagent to the overcoated gold surface. The
      results show that interactions with gold can be blocked by a silane layer so as
      not to significantly influence physisorption of molecules at the C-18/solution
      interface. The SERS enhancement from these C-18-overcoated gold substrates is
      reproducible for different films prepared from the same colloidal suspension; the
      substrates are also stable with time and upon exposure to laser irradiation.

PMID- 11569818
TI  - Quantification of the concentration of ionic impurities in polymeric sensing
      membranes with the segmented sandwich technique.
AB  - Ionic impurities in solvent polymeric membranes have been the main reason early
      ion-selective electrodes (ISEs) without added ion exchanger exhibited a
      functional potentiometric response. Today, knowledge of such impurities and their
      elimination becomes important in view of designing ISEs with low detection limits
      and voltammetric ion-selective electrodes, to increase operational lifetime, and
      to optimize sensing selectivity. Here, a potentiometric segmented sandwich
      membrane technique is used to study the amount and properties of impurities in
      situ directly in the membrane phase. This technique can be used with a number of
      ionophores and with different membrane matrixes and does not require specialized
      equipment. The concentration of anionic impurities in PVC-DOS (bis(2-ethylhexyl)
      sebacate) and PVC-NPOE (o-nitrophenyloctyl ether) was found to be on the order of
      100 micromol/kg with membranes containing weakly binding potassium ionophores.
      The concentration of cation-exchanger sites of carboxylated PVC-NPOE was found to
      be higher (1.62 mmol/kg). Addition of the neutral lipophilic salt ETH 500 to both
      membrane segments had only a marginal effect on the results for PVC-NPOE
      membranes but had a large impact on the observed membrane potential for PVC-DOS
      membranes. Theory explains that the addition of such salt to membranes where ion
      pairing is predominant is essential for the accurate assessment of ionic
      impurities with this technique.

PMID- 11569820
TI  - Long-wavelength long-lifetime luminophores.
AB  - We describe a new approach to making luminophores that display long emission
      wavelengths, long decay times, and high quantum yields. These luminophores are
      covalently linked pairs with a long-lifetime resonance-energy-transfer donor and
      a long-wavelength acceptor. The donor was a ruthenium (Ru) metal-ligand complex.
      The acceptor was the Texas Red. The donor and acceptor were covalently linked by
      polyproline spacers. The long-lifetime donor results in a long-lived component in
      the acceptor decay, which is due to RET. Importantly, the quantum yield of the
      luminophores approaches that of the higher quantum yield acceptor, rather than
      the lower quantum yield typical of metal-ligand complexes. The emission maxima
      and decay time of such tandem luminophores can be readily adjusted by selection
      of the donor, acceptor, and distance between them. Luminophores with these useful
      spectral properties can also be donor-acceptor pairs brought into close proximity
      by some biochemical association reaction. Luminophores with long-wavelength
      emission and long lifetimes can have numerous applications in biophysics,
      clinical diagnostics, DNA analysis, and drug discovery.

PMID- 11569821
TI  - Quantitative analysis of low-field NMR signals in the time domain.
AB  - Two novel methods are described for direct quantitative analysis of NMR free
      induction decay (FID) signals. The methods use adaptations of the generalized
      rank annihilation method (GRAM) and the direct exponential curve resolution
      algorithm (DECRA). With FID-GRAM, the Hankel matrix of the sample signal is
      compared with that of a reference mixture to obtain quantitative data about the
      components. With FID-DECRA, a single-sample FID matrix is split into two
      matrices, allowing quantitative recovery of decay constants and the individual
      signals in the FID. Inaccurate results were obtained with FID-GRAM when there
      were differences between the frequency or transverse relaxation time of signals
      for the reference and test samples. This problem does not arise with FID-DECRA,
      because comparison with a reference signal is unnecessary. Application of FID
      DECRA to 19F NMR data, which contained overlapping signals from three components,
      gave concentrations comparable to those derived from partial least squares (PLS)
      analysis of the Fourier transformed spectra. However, the main advantage of FID
      DECRA was that accurate (<5% error) and precise (2.3% RSD) results were obtained
      using only one calibration sample, whereas with PLS, a training set of 10
      standard mixtures was used to give comparable accuracy and precision.

PMID- 11569822
TI  - Use of capillary gas chromatography with negative ion-chemical ionization mass
      spectrometry for the determination of perfluorocarbon tracers in the atmosphere.
AB  - A sensitive and selective technique for the quantitative measurement of
      atmospheric perfluorocarbon trace species at the sub part per quadrillion (10(
      15)) levels is presented. The method utilizes advances in adsorbent enrichment
      techniques coupled with benchtop capillary gas chromatography and negative ion
      chemical ionization mass spectrometry. The development and enhancement of
      sampling technology for tracer experiments is described, and the results from
      background measurements and a preliminary field experiment are presented. The
      overall precision of the analytical method with respect to the preferred tracer
      for these atmospheric transport studies, perfluoromethylcyclohexane, was +/-1.7%.
      The background concentrations of perfluorodimethylcyclobutane,
      perfluoromethylcyclopentane, and perfluoromethylcyclohexane at a remote coastal
      location (Mace Head, Ireland, 53 degrees N, 10 degrees W) were found to be 2.5
      (+/-0.4), 6.8 (+/-1.0), and 5.2 fL L(-1) (+/-1.3), respectively. Background
      concentrations within an urban conurbation (Bristol, U.K.) were slightly greater
      at 3.0 (+/-1.5), 8.1 (+/-1.8), and 6.3 fL L(-1) (+/-1.1), respectively.

PMID- 11569823
TI  - Prediction of the chemiluminescent behavior of pharmaceuticals and pesticides.
AB  - The present paper deals with the first attempt to apply molecular connectivity
      calculations to predict a chemical property with analytical usefulness: the
      chemiluminescent behavior of substances when reacted with common oxidants in a
      liquid phase. Preliminary evidence when searching for new direct CL methods
      consisted of the examination of analyte reaction with a wide range of oxidants
      and media. This task, which results in time-consuming and trial-and-error
      expensive procedures, is necessary due to ensure empirical or theoretical rules
      for CL prediction are available. On the other hand, in quantitative structure
      activity relationship studies, molecular connectivity is a topological method
      capable of describing the structure of a molecule by means of numbers named
      indices; subsequent regression in relation to the experimental values of the
      physical, chemical, or biological properties yields a series of functions called
      connectivity functions. Discriminant analysis was applied to 200 either
      chemiluminescent or nonchemiluminescent substances found either bibliographically
      or in an experimental screening. The method used for the selection of descriptors
      was a stepwise linear discriminant analysis from the Snedecor F-parameter. The
      classification criterion used was the minimum value of Mahalanobis. The quality
      of the discriminant function was calculated through the Wilks U-statistical
      parameter. Finally, the function was applied to a database including of more than
      50,000 structurally heterogeneous compounds. The theoretical predictions were
      faced with the empirical evidence obtained through a continuous-flow manifold.

PMID- 11569824
TI  - Total internal reflected resonance light scattering determination of
      chlortetracycline in body fluid with the complex cation of chlortetracycline
      europium-trioctyl phosphine oxide at the water/tetrachloromethane interface.
AB  - A highly selective method of chlortetracycline (CTC) is proposed on the basis of
      the measurements of total internal reflected resonance light scattering (TMR-RLS)
      at water/tetrachloromethane (H20/CCl4) interfaces. In the pH range of 7.54-8.14,
      the interaction of the binary complex of Eu(III)/CTC in the presence of trioctyl
      phosphine oxide (TOPO) occurs at the H20/CCl4 interface, resulting in greatly
      enhanced TIR-RLS signals with the maximum peak located at 340 nm. The enhanced
      TIR-RLS intensity is in proportion to the CTC concentration in the range 0.98 to
      approximately 20.0 x 10(-7) mol/L. The limit of detection is 9.8 x 10(-9) mol/L.
      Synthetic samples and body fluid samples including human urine, human serum, and
      fresh milk were determined with the recovery of 95.4-106.4% and RSD of 2.9-3.9%.

PMID- 11569825
TI  - Optical biosensors. Monitoring studies of glycopeptide antibiotic fermentation
      using white light interference.
AB  - This paper describes the design, characterization, and use of an optical
      biosensor suited for the process control of biotechnological processes. The
      detector principle is based on reflectometric interference spectroscopy (RIfS).
      RIfS enables a label-free, product-specific monitoring, with a future outline for
      on-line process control. The potential of the RIfS biosensor is exemplified by
      the qualitative and quantitative monitoring of the microbial production of
      vancomycin-type glycopeptide antibiotics.

PMID- 11569826
TI  - Direct and simultaneous determination of copper, chromium, aluminum, and
      manganese in urine with a multielement graphite furnace atomic absorption
      spectrometer.
AB  - A simple method was developed for the direct and simultaneous determination of
      copper, chromium, aluminum, and manganese in urine using a multielement GFAAS
      (Perkin-Elmer SIMAA6000). Pd was used as the chemical modifier along with a
      special purge gas (5% H2 in Ar). A simple calibration curve method can be used
      (with 1:1 dilution). A standard reference material (Seronorm Trace Elements
      Urine) was used to find the optimal temperature program and to confirm the
      accuracy of the technique. The analyzed values were within 90-110% of the
      certified values. The relative standard deviations were 1.7, 1.5, 1.6, and 1.5%
      for these four elements and the detection limits were 0.08 microg L(-1) for Cu,
      0.05 microg L(-1) for Cr, 0.06 microg L(-1) for Al, and 0.06 microg L(-1) for Mn.
      The recoveries of Cu, Cr, Al, and Mn from real urine samples were 100 +/- 5%,
      except for Cu (80%). The found values of Cu, Cr, Al, and Mn in a real urine
      sample were 14.3, 0.78, 18.9, and 0.06 microg L(-1), respectively. Scanning
      electron micrographs were used to investigate the physical form of Pd on the
      surface of the platform in the graphite furnace. Use of 5% H2 in Ar as the purge
      gas resulted in smaller and more uniformly distributed Pd particles (Pd particle
      diameters 0.4-0.6 microm using 5% H2 in Ar compared to 0.4-1.2 microm using pure
      Ar), increasing the effect of the Pd chemical modifier and promoting the
      efficiency of atomization.

PMID- 11569827
TI  - Comparison of multianalyte immunosensor formats for on-line determination of
      organic compounds.
AB  - Studies leading to the development of multianalyte immunosensing approaches are
      presented herein. Competitive capture formats are developed for carbaryl,
      atrazine, and irgarol 1051 as target compounds. Three proposals have been tested:
      sequential, additive, and simultaneous formats. For individual determinations,
      the best format is the sequential mode; the additive mode is useful only for
      qualitative analyses; and the simultaneous mode is preferable for screening
      purposes. The proposed systems show to be advantageous over single-analyte
      sensors and other multianalyte approaches. In all cases, the sensitivity reached
      (limit of detection) is high enough for the analysis of samples containing levels
      of each pesticide lower than 0.1 microg/L, and sensor reusability is very good
      (>600 determinations). The applicability of the multianalyte immunosensors to on
      line pollution surveillance in natural waters, as well as their advantages and
      limitations, is discussed.

PMID- 11569828
TI  - Assay of spherical cell surface molecules by thermal lens microscopy and its
      application to blood cell substances.
AB  - To detect and quantitate uneven cell surface molecules, such as blood group
      antigens on a blood cell and immunoglobulin molecules on a mast cell, an improved
      method of thermal lens microscopy was employed. The antigen molecules were
      immunologically stained with their antibodies, which were labeled with colloidal
      gold. Since the surface of the biological cells was not flat but spherical, the
      focal point of the probe laser beam inevitably deviated from the sample surface
      on the moving stage. Therefore, the deviation of the focal point of the probe
      beam was corrected by adjusting the phase of the signal. Using this technique, a
      three-dimensional antigen distribution on each cell surface was imaged. Despite
      the convex surface of cells, labeled colloidal gold was correctly quantified. In
      the measurement of erythrocyte antigens, a small quantity of Lewis antigens was
      successfully detected on the umbilical cord erythrocytes. Immunoglobulin E on a
      mast cell, derived from the allergic human mucosa fungus, was also observed by
      this method, and the distribution of IgE molecules on the cell surface was
      quantitatively imaged. A thermal lens microscope, which measures spherical
      samples correcting the deviation, made it possible for us to observe and assay
      the substances on biological specimens that have complicated forms, such as
      living cells in vivo or in situ.

PMID- 11569829
TI  - Size characterization of bentonite colloids by different methods.
AB  - The size and shape of colloids released from a natural bentonite into a low
      mineralized groundwater are investigated using various colloid characterization
      methods. For the applied methods such as atomic force microscopy (AFM), laser
      induced breakdown detection (UBD), photon correlation spectroscopy (PCS), and
      flow field-flow fractionation coupled to ICP-mass spectrometric detection (FFFF
      ICPMS), the respective raw size data have to be corrected in order to consider
      chemical composition and shape of the colloids as well as instrumental artifacts.
      Noncontact mode AFM of the bentonite colloids shows disklike shapes of stacked
      smectite platelets with a mean height-to-diameter proportion (aspect ratio) of
      approximately 1/10. A broad particle number size distribution is determined by
      image processing with a mean particle diameter of 73 nm. In agreement with AFM, a
      broad size distribution is also found by PCS and FFFF-ICPMS. Likewise, mean
      particle sizes found by LIBD (67 +/- 13 nm) and FFFF-ICPMS (maximum in the number
      size distribution, approximately 70 nm) are in fair agreement with the AFM data.
      Somewhathigher values are obtained by PCS, where mean particle diameters of the
      intensity-weighted size distributions of larger than 200 nm are found (depending
      on the algorithm used for data processing). The influence of the disklike
      particle shape on the results of the individual methods is discussed. As a
      conclusion, the application of different colloid characterization methods is a
      prerequisite to get complementary information about colloid size and shape, which
      is essential for the understanding of natural colloidal systems.

PMID- 11569830
TI  - Evaluation of depth profiling using laser resonant desorption as a method to
      measure diffusion coefficients in ice.
AB  - Diffusion of gases in ice is involved in cloud, snow, and ice core chemistry, but
      few data exist on the relevant diffusion coefficients. A novel method to measure
      diffusion coefficients in ice has recently been proposed by Livingston et al.
      (Anal. Chem., 2000, 72, 5590-5599). It is based on depth profiling of doped ice
      crystals epitaxially grown on Ru(001) by laser resonant desorption (LRD). Using
      this method, Livingston et al. obtained a value of the diffusion coefficient of
      the HCl hydrate in ice at 190 K of about 5 x 10(-11) cm2/s. We argue here that
      this value is many orders of magnitude higher than what could be expected from
      literature values, which are not reported in sufficient detail by Livingston et
      al. We investigate the possibilities that their high value could be due to (1)
      diffusion in defects in the ice, which would be present in very high
      concentrations because of the ice growth method; and (2) the fact that diffusion
      of high concentrations of HCl in ice at 190 K forms an amorphous HCl:H2O solid
      mixture, where HCl diffusion is fast. We present new infrared spectroscopic data
      on solid HCl:H2O mixtures that confirm that such mixtures can indeed be formed in
      an amorphous state at 190 K. Our proposed interpretation is that by depositing
      large amounts of HCl on epitaxially grown ice, Livingston et al. created a
      superficial amorphous binary mixture and that fast diffusion of HCl in the ice,
      possibly accelerated by a high defect density, produced an amorphous HCl:H2O
      mixture. We conclude that the processes studied by Livingston et al. are
      different from those involved in the atmospheric and cryospheric sciences, and
      that their data, obtained by depth profiling using LRD, probably cannot be
      applied to those fields.

PMID- 11569831
TI  - Fluorescent imaging of pH with optical sensors using time domain dual lifetime
      referencing.
AB  - We present a referenced scheme for fluorescence intensity measurements that is
      useful for imaging applications. It is based on the conversion of the
      fluorescence intensity information into a time-dependent parameter. A
      phosphorescent dye is added in the form of approximately 10-microm particles to
      the sample containing the pH-sensitive fluorescent indicator. Both the reference
      dye and the pH probe are excited simultaneously by a blue LED, and an overall
      luminescence is measured. In the time-resolved imaging method presented here, two
      images taken at different time gates were recorded using a CCD camera. The first
      image is recorded during excitation and reflects the luminescence signal of both
      the fluorophore (pH) and the phosphor (reference). The second image, which is
      measured after a certain delay (after switching off the light source), is solely
      caused by the long-lived phosphorescent dye. Because the intensity of the
      fluorophore contains the information on pH, whereas phosphorescence is pH
      independent, the ratio of the images displays a referenced intensity distribution
      that reflects the pH at each picture element (pixel). The scheme is useful for
      LED light sources and CCD cameras that can be gated with square pulses in the
      microsecond range. The fundamentals and potential of this new method, to which we
      refer as time domain dual lifetime referencing (t-DLR), are demonstrated.

PMID- 11569832
TI  - Spike removal and denoising of Raman spectra by wavelet transform methods.
AB  - Wavelet decompositions of Raman spectra were investigated with respect to their
      usability for spike removal and denoising of the raw data. It could be shown that
      those operations should be performed sequentially. Suppression of spikes is not
      straightforwardly possible by wavelet transformation; however, the wavelet
      transform may be used to recognize the spikes by their first level detail
      coefficients. Spike locations could be projected from the details to the
      approximations and, further, to appropriate locations of the original spectrum.
      After spike recognition, those regions will be replaced by interpolated values.
      To complete processing, denoising is performed with the despiked spectrum by
      repeated application of wavelet transform methods.

PMID- 11569833
TI  - Attenuated total reflection design for in situ FT-IR spectroelectrochemical
      studies.
AB  - A versatile spectroelectrochemical apparatus is introduced to study the changes
      in IR spectra of organic and inorganic compounds upon oxidation or reduction. The
      design is based on an attenuated total reflection device, which permits the study
      of a wide spectral range of 16,700 (600 nm)-250 cm(-1), with a small opaque
      region of 2250-1900 cm(-1). In addition, an IR data collection protocol is
      introduced to deal with electrochemically nonreversible background signals. This
      method is tested with ferrocene in acetonitrile; concentrations as low as 1 mM
      produce results that agree with those in the literature.

PMID- 11569834
TI  - Analysis of aromatic aldehydes in brandy and wine by high-performance capillary
      electrophoresis.
AB  - A new method of analysis of vanillin, syringaldehyde, coniferaldehyde, and
      sinapaldehyde in brandy and wine by high-performance capillary electrophoresis is
      described. Electrophoretic mobility of these compounds is achieved by a borate
      buffer at pH 9.3. At this pH, the sensitivity of UV detection of these phenolic
      aldehydes also increases. UV absorptions at 348, 362, 404, and 422 nm were
      selected for monitoring vanillin, syringaldehyde, coniferaldehyde, and
      sinapaldehyde, respectively. This procedure was performed simultaneously during
      one run using a diode array detector. Samples of brandy or wine were analyzed
      directly without concentration, extraction, or any other preliminary treatment of
      the test sample. The limits of detection were found to be 0.275, 0.1425, 0.1475,
      and 0.1975 ppm for syringaldehyde, coniferaldehyde, sinapaldehyde, and vanillin,
      respectively, which is acceptable for analysis of both brandy and wine aged in
      oak barrels. The method has been shown to be linear in a range from 0.3 to 57
      mg/L. Recoveries ranged between 99.9% and 107.7% for all of the compounds tested.
      Repeatability and reproducibility of the method were high. The relative standard
      deviation was consequently approximately 3% and also between 4.47% and 6.89% for
      all tested compounds. The method is useful for the identification of counterfeit
      brandy, which is easy to recognize by the absence of sinapaldehyde,
      syringaldehyde, and coniferaldehyde, which are not detectable in false brandy.

PMID- 11569835
TI  - Electrochemistry in the presence of convective flow generated by acoustic
      streaming from a focused ultrasonic source.
AB  - Limiting currents for the reduction of hexacyanoferrate-(III), i(lim), in aqueous
      solutions have been recorded in the presence of convective flow generated by a
      focused acoustic source with its main axis placed normal to the surface of a
      circular Au electrode embedded in a coplanar Teflon shroud. The results obtained
      could be fitted to a formula of the type -i(lim) = a(Uz(ss))b, where Uz(ss) is
      the axial velocity of the fluid along the center line of the lens evaluated at
      the focal point using computer simulation routines developed by Kamakura and co
      workers (Kamakura, T.; Matsuda, K; Kumamoto, Y.; Breazeale, M. A. J. Acoust. Soc.
      Am. 1995, 97, 2740-2746). The fit yielded a value of b approximately 0.5 in
      agreement with that of rotating disk and impinging jet electrodes.

PMID- 11569836
TI  - Development of a flow injection capillary chemiluminescent ELISA using an
      imprinted polymer instead of the antibody.
AB  - A flow injection competitive assay analogous to enzyme immunoassays has been
      developed using a molecularly imprinted polymer instead of the antibody. A glass
      capillary was modified by covalently attaching an imprinted polymer to the inner
      capillary wall. The herbicide 2,4-dichlorophenoxyacetic acid was used as a model
      analyte. The analyte was labeled with tobacco peroxidase, and chemiluminescence
      was used for detection in combination with a photomultiplier tube or a CCD
      camera. In a competitive mode, the analyte-peroxidase conjugate was passed
      together with the free analyte through the polymer-coated capillary mounted in a
      flow system. After a washing step, the chemiluminescent substrate was injected
      and the bound fraction of the conjugate was quantified by measuring the intensity
      of the emitted light. Calibration curves corresponding to analyte concentrations
      ranging from 0.5 ng mL(-1) to 50 microg mL(-1) (2.25 nM-225 microM) were
      obtained. A lowered detection limit by 2 orders of magnitude was obtained when
      detection was done in discontinuous mode and the chemiluminescence light was
      conducted inside the photomultiplier tube by an optical fiber bundle, thus
      yielding a dynamic range of 5 pg mL(-1)-100 ng mL(-1) (22.5 pM-450 nM).

PMID- 11569837
TI  - The size of future science libraries.

PMID- 11569838
TI  - Virtual 2-D proteomics.

PMID- 11569840
TI  - CD optode detects ions.

PMID- 11569839
TI  - Electroporating single cells.

PMID- 11569841
TI  - 25th International Symposium on High-Performance Liquid-Phase Separations and
      Related Techniques (HPLC 2001).

PMID- 11569842
TI  - U.S. science funding shortfall.

PMID- 11569843
TI  - Promoting British analytical chemistry.

PMID- 11569844
TI  - Pulsed glow discharge: temporal resolution in analytical spectroscopy.

PMID- 11569845
TI  - Miniaturization of enantioselective detectors.

PMID- 11569846
TI  - Capillary electrophoresis: finding a niche.

PMID- 11569847
TI  - Problem-based learning: in need of supporting materials.

PMID- 11569848
TI  - Proximal tibial fractures--should we nail them?
AB  - Intramedullary nails (IMNs) are the treatment of choice for diaphyseal tibial
      fractures. Its use has been expanded both distally and proximally to cover
      metaphyseal fractures at both ends of the tibia. Several authors have stated that
      IMN use in proximal tibial fractures (extra-articular) can become problematic,
      leading to a significantly increased rate of malunion. Different strategies for
      solving this problem have been reported in recent years, but no strategy is fault
      free. We review the causes of and solutions for increased malunion following use
      of IMNs for proximal tibial fractures.

PMID- 11569849
TI  - Hybrid advanced Ilizarov techniques: analgesia use and patient satisfaction.
AB  - Patients involved in the initial Western application of the Ilizarov technique
      experienced frequent pain and could not tolerate the device. With "hybrid
      advanced" Ilizarov techniques, half-pins and other components are added to
      minimize these adverse reactions. In this study of advanced techniques, we
      determined patient satisfaction (with end results), device tolerance, pain
      levels, and need for analgesia. These techniques used at least 1 half-pin on each
      ring--except for the distal tibial ring, which had 3 transfixing wires-
      perpendicular to either another half-pin or a transfixing wire. Eighty-one
      consecutive patients treated with advanced techniques were prospectively studied
      until the treatment was completed and the device removed. All patients received
      intravenous analgesia while hospitalized. Narcotic and non-narcotic analgesia was
      available to all patients, and analgesia use was measured. In addition, patient
      satisfaction and pain level were recorded. All patients were satisfied with end
      results and tolerated the device prescribed by their physician. Mean
      postoperative hospitalization was 5.1 days. Upon discharge from the hospital, 3
      patients (3.7%) with moderate pain used postoperative narcotics for a mean of 6
      days (range, 1-11 d), and 41 patients (50.6%) with mild pain used over-the
      counter non-narcotic analgesia or prescription antiinflammatory medication for a
      mean of 4.4 days (range, 1-35 d). The other 37 patients (45.7%) were comfortable
      and did not require analgesia. In general, patients undergoing hybrid-advanced
      Ilizarov techniques infrequently needed postoperative analgesia.

PMID- 11569850
TI  - Avulsion fracture of the origin of the brachioradialis muscle.
AB  - Avulsion fracture of the brachioradialis muscle from its origin on the lateral
      supracondylar ridge of the humerus has not previously been reported in the
      literature. In this article, we present the case of a patient who sustained a
      grade I open avulsion fracture of the lateral supracondylar ridge of the humerus.
      The mechanism by which this fracture occurred is proposed on the basis of the
      structure and function of the brachioradialis muscle.

PMID- 11569852
TI  - Lateral patellar chamfer in total knee arthroplasty.
AB  - Derangement of the anterior compartment of the knee can cause patellofemoral
      dysfunction in up to 50% of secondary surgeries after total knee arthroplasty. A
      technique of patellar chamfering is described that can minimize the risk of
      anterior knee pain from lateral patellar impingement without compromising bone
      stock for future operations.

PMID- 11569853
TI  - Septic arthritis.

PMID- 11569851
TI  - Proximal ulna shaft fractures and associated compartment syndromes.
AB  - In 1996, 6 (7%) of 84 ulna shaft fractures treated at our institution developed
      compartment syndrome. These 6 isolated, comminuted, proximal-third ulna fractures
      were secondary to low-velocity gunshot (5) or high-velocity blunt trauma (1). The
      5 gunshot-induced fractures did not initially require immediate surgical
      intervention, but increasing compartment pressure prompted fasciotomy and open
      reduction and internal fixation. The blunt trauma fracture developed compartment
      syndrome while the patient awaited surgery; emergent fasciotomy and open
      reduction and internal fixation were performed. Three patients had vascular
      injury (interosseus system). The orthopedist must have a high index of suspicion
      for compartment syndrome in association with isolated, comminuted, proximal-third
      ulna fractures.

PMID- 11569854
TI  - Metals in environmental compartments. Reflections on the 8th Workshop on Progress
      in Analytical Methodologies for Trace Metal Speciation, Lisbon, Portugal,
      September 5, 2000.

PMID- 11569855
TI  - Molecularly imprinted polymers: new molecular recognition materials for selective
      solid-phase extraction of organic compounds.
AB  - During the last few years molecularly imprinted polymers have appeared as new
      selective sorbents for solid-phase extraction of organic compounds in different
      samples. Molecular imprinting technology involves the preparation of a polymer
      with specific recognition sites for certain molecules. Once the polymer has been
      obtained, it can be used in solid-phase extraction protocols, where a careful
      selection of the most appropriate solvents to be used in the different steps
      (sample loading, washing and elution) is needed in order to extract the target
      analyte selectively. This review describes the state of the art of this
      methodology, including the preparation of imprinted polymers, a process
      description for molecularly imprinted solid-phase extraction, as well as more
      recent applications. It is concluded that molecularly imprinted solid-phase
      extraction is a powerful tool to selectively isolate certain analytes, and future
      advances are to be expected in order to widen the field of application.

PMID- 11569856
TI  - web-based interactive data processing: application to stable isotope metrology.
AB  - To address a fundamental need in stable isotope metrology, the National Institute
      of Standards and Technology (NIST) has established a web-based interactive data
      processing system accessible through a common gateway interface (CGI) program on
      the internet site http://www. nist.gov/widps-co2. This is the first application
      of a web-based tool that improves the measurement traceability afforded by a
      series of NIST standard materials. Specifically, this tool promotes the proper
      usage of isotope reference materials (RMs) and improves the quality of reported
      data from extensive measurement networks. Through the International Atomic Energy
      Agency (IAEA), we have defined standard procedures for stable isotope measurement
      and data-processing, and have determined and applied consistent reference values
      for selected NIST and IAEA isotope RMs. Measurement data of samples and RMs are
      entered into specified fields on the web-based form. These data are submitted
      through the CGI program on a NIST Web server, where appropriate calculations are
      performed and results returned to the client. Several international laboratories
      have independently verified the accuracy of the procedures and algorithm for
      measurements of naturally occurring carbon-13 and oxygen-18 abundances and
      slightly enriched compositions up to approximately 150% relative to natural
      abundances. To conserve the use of the NIST RMs, users may determine value
      assignments for a secondary standard to be used in routine analysis. Users may
      also wish to validate proprietary algorithms embedded in their laboratory
      instrumentation, or specify the values of fundamental variables that are usually
      fixed in reduction algorithms to see the effect on the calculations. The results
      returned from the web-based tool are limited in quality only by the measurements
      themselves, and further value may be realized through the normalization function.
      When combined with stringent measurement protocols, two- to threefold
      improvements have been realized in the reproducibility of carbon-13 and oxygen-18
      determinations across laboratories.

PMID- 11569857
TI  - Collaborative study to improve the quality control of trace element
      determinations in polymers. Part 2. Certification of polyethylene reference
      materials (CRMs 680 and 681) for As, Br, Cd, Cl, Cr, Hg, Pb, and S content.
AB  - Two polymer (polyethylene) reference materials have been produced in support of
      EC Directive 94/62/EC on plastic packaging and packaging material. The paper
      describes the preparation of the materials, the analytical work performed to
      characterize their homogeneity and stability, and the certification of the
      materials for a range of elements. The technical and statistical evaluation of
      the results are also summarized.

PMID- 11569858
TI  - Preparation of calibration materials for microanalysis of Ti minerals by direct
      fusion of synthetic and natural materials: experience with LA-ICP-MS analysis of
      some important minor and trace elements in ilmenite and rutile.
AB  - Calibration materials for microanalysis of Ti minerals have been prepared by
      direct fusion of synthetic and natural materials by resistance heating in high
      purity graphite electrodes. Synthetic materials were FeTiO3 and TiO2 reagents
      doped with minor and trace elements; CRMs for ilmenite, rutile, and a Ti-rich
      magnetite were used as natural materials. Problems occurred during fusion of
      Fe2O3-rich materials, because at atmospheric pressure Fe2O3 decomposes into Fe3O4
      and O2 at 1462 degrees C. An alternative fusion technique under pressure was
      tested, but the resulting materials were characterized by extensive segregation
      and development of separate phases. Fe2O3-rich materials were therefore fused
      below this temperature, resulting in a form of sintering, without conversion of
      the materials into amorphous glasses. The fused materials were studied by optical
      microscopy and EPMA, and tested as calibration materials by inductively coupled
      plasma mass spectrometry, equipped with laser ablation for sample introduction
      (LA-ICP-MS). It was demonstrated that calibration curves based on materials of
      rutile composition, within normal analytical uncertainty, generally coincide with
      calibration curves based on materials of ilmenite composition. It is, therefore,
      concluded that LA-ICP-MS analysis of Ti minerals can with advantage be based
      exclusively on calibration materials prepared for rutile, thereby avoiding the
      special fusion problems related to oxide mixtures of ilmenite composition. It is
      documented that sintered materials were in good overall agreement with
      homogeneous glass materials, an observation that indicates that in other
      situations also sintered mineral concentrates might be a useful alternative for
      instrument calibration, e.g. as alternative to pressed powders.

PMID- 11569859
TI  - Development of perfluorocarbon (PFC) primary standards for monitoring of
      emissions from aluminum production.
AB  - An EPA Voluntary Aluminum Industrial Partnership (VAIP) program has been formed
      to help US primary producers focus on reducing the emissions of two
      perfluorocarbons (PFCs), tetrafluoromethane (CF4) and hexafluoroethane (C2F6),
      during the production of aluminum. To ensure comparability of measurements over
      space and time, traceability to national sources was desirable. Hence, the EPA
      approached the NIST to develop a suite of primary standards to cover a mole
      fraction (concentration) range of 0.1 to 1400 micromol mol(-1) for CF4 and 0.01
      to 150 micromol mol(-1) of C2F6. A total of eight gravimetric PFC gas standards
      were prepared with relative expanded uncertainties of < or = 0.52% (approximately
      95% confidence level). These primary standards were ultimately used to assign
      values to a series of secondary gas standards at three mole-fraction levels with
      relative expanded uncertainties ranging from +/- 0.7% to 5.3% (approximately 95%
      confidence level). This series of secondary standards was used within the
      aluminum industry to calibrate instruments used to make emission measurements.
      Assignment of values to the secondary standards was performed by use of gas
      chromatography with flame-ionization detection (GC-FID) and Fourier transform
      infrared spectrometry (FTIR). Real time pot-line and stack samples from a local
      aluminum plant were also obtained and sub-samples sent to each participating
      facility for analysis. The data generated from each facility were sent to NIST
      for analysis. The maximum difference between the NIST and individual facilities'
      values for the same sub-sample was +/- 26%.

PMID- 11569860
TI  - Determination of As, Cd, Cr, and Hg in SRM 2584 (trace elements in indoor dust)
      by high-resolution inductively coupled plasma mass spectrometry.
AB  - Standard reference material (SRM) 2584 (Trace Elements in Indoor Dust) was
      developed as a reference standard for evaluating field methods and for validating
      laboratory and reference methods for the assessment of lead contamination and
      exposure. In addition to lead, the toxic trace elements As, Cd, Cr, and Hg, at
      approximately 17, 10, 140, and 5 microg g(-1), respectively, have been certified
      in the SRM. These four analytes were successfully determined by use of high
      resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). Isobaric
      interferences at masses of As and Cr were resolved by using the high resolution
      mode (nominal 8000) and the medium resolution mode (nominal 3000), respectively,
      of the instrument. The effects of a significant drift in analyte sensitivity in
      the course of measurement were rectified by use of internal standardization,
      single spike standard addition, and an optimized analysis sequence. The results
      were compared with those obtained by instrumental neutron activation analysis
      (INAA) and isotope dilution inductively coupled plasma mass spectrometry (ID-ICP
      MS). The results for the quality control, SRM 2704 (Buffalo River Sediment), were
      in good agreement with the certified values, indicated by the uncertainty
      intervals of the measured values overlapping the certified intervals at 95%
      confidence level.

PMID- 11569861
TI  - The development and certification of Standard Reference Materials (SRMs) to
      assess and ensure accurate measurement of Pb in the environment.
AB  - The National Institute of Standards and Technology (NIST) has had a major quality
      assurance role in the federal effort to reduce lead poisoning of children in the
      United States through its mission of ensuring the accuracy of chemical
      measurements. NIST certifies reference materials (standard reference materials-
      SRMs) that are used to benchmark measurements by secondary and field methods of
      analysis--to ensure that decisions of great health and economic impact are
      soundly based on good measurement science. Over the past 10 years, in cooperation
      with the US Environmental Protection Agency (EPA), US Department of Housing and
      Urban Development (HUD), and the United States Geological Survey (USGS), NIST has
      prepared and certified SRMs for lead content in soil, indoor dust, and paint. The
      role of these materials in meeting regulatory and abatement needs is described
      and their certified values are summarized.

PMID- 11569862
TI  - Analyte transport efficiencies in electrothermal vaporization for inductively
      coupled plasma mass spectrometry.
AB  - A modified graphite furnace for solid-sampling atomic absorption spectrometry as
      an electrothermal vaporizer (ETV) was coupled to a Perkin-Elmer/Sciex ELAN 6000
      ICP mass spectrometer. The integrals obtained from electrothermal vaporization of
      aliquots containing As, Cd, Cu, Co, Fe, Mn, Pb, Se, and Zn were compared with
      those obtained from pneumatic nebulization of the same aqueous standard solution.
      The pneumatic nebulizer was calibrated by weighing the mass of aqueous aerosol
      trapped on a filter. With "wet plasma" conditions maintained also for
      measurements with the ETV and reference signals for analyte signals obtained with
      the calibrated pneumatic nebulization, the transport efficiency of the ETV
      system, e.g. the ratio of the analyte amount introduced into the plasma to that
      amount dosed into the vaporizer, was determined. The transport efficiency of two
      different tube and interface designs has been evaluated. Investigations with and
      without the use of trifluoromethane as reactive gas, with different furnace
      heating rates, and with varying gas flows were performed. In general, the tube
      equipped with a nozzle led to generally higher transport efficiency than the
      standard tube. Without trifluoromethane transport efficiencies ranged from 10% to
      35% with the standard tube and from 15% to 50% with the nozzle-type tube. With
      addition of 2 mL min(-1) trifluoromethane to the argon flow of 400 mL min(-1)
      through the tube, transport efficiencies from 20% to 70% and from 70% to 100%
      were achieved with the standard and nozzle-type tubes, respectively.

PMID- 11569863
TI  - Determination of selenium in soils by slurry-sampling graphite-furnace atomic
      absorption spectrometry with polytetrafluoroethylene as silica modifier.
AB  - A 6% slurry of polytetrafluoroethylene (PTFE) in 4% hydrofluoric acid and 1%
      nickel nitrate were used as modifiers for determination of selenium in soils by
      GF AAS. PTFE was used to remove silica from the soil sample, because this
      resulted in severe matrix effects. The temperature of fluorination, determined
      thermogravimetrically, was 600 degrees C. The yield of fluorination depends on
      the molar ratio of PTFE/silica, particle size, and the time and temperature of
      fluorination. The soil samples were pretreated with a small amount of
      concentrated hydrofluoric acid placed directly in the cup of autosampler. The
      results for the determination of selenium in the reference soil materials by
      means of the slurry-sampling technique and use of aqueous standards are in good
      agreement with the certified values.

PMID- 11569864
TI  - Direct determination of silicon in powdered aluminium oxide by use of slurry
      sampling with in situ fusion graphite-furnace atomic-absorption spectrometry.
AB  - A direct method for determination of silicon in powdered high-purity aluminium
      oxide samples, by slurry sampling with in situ fusion graphite-furnace atomic
      absorption spectrometry (GF-AAS), has been established. A slurry sample was
      prepared by 10-min ultrasonication of a powdered sample in an aqueous solution
      containing both sodium carbonate and boric acid as a mixed flux. An appropriate
      portion of the slurry was introduced into a pyrolytic graphite furnace equipped
      with a platform. Silicon compounds to be determined and aluminium oxide were
      fused by the in situ fusion process with the flux in the furnace under optimized
      heating conditions, and the silicon absorbance was then measured directly. The
      calibration curve was prepared by use of a silicon standard solution containing
      the same concentration of the flux as the slurry sample. The accuracy of the
      proposed method was confirmed by analysis of certified reference materials. The
      proposed method gave statistically accurate values at the 95% confidence level.
      The detection limit was 3.3 microg g(-1) in solid samples, when 300 mg/20 mL
      slurry was prepared and a 10 microL portion of the slurry was measured. The
      precision of the determination (RSD for more than four separate determinations)
      was 14% and 2%, respectively, for levels of 10 and 100 microg g(-1) silicon in
      aluminium oxide.

PMID- 11569865
TI  - Preconcentration by coprecipitation of arsenic and tin in natural waters with a
      Ni-pyrrolidine dithiocarbamate complex and their direct determination by solid
      sampling atomic-absorption spectrometry.
AB  - A method for the determination of trace amounts of arsenic and tin in natural
      waters is described. Trace amounts of arsenic and tin were preconcentrated by
      coprecipitation with a Ni-ammonium pyrrolidine dithiocarbamate (APDC) complex.
      The coprecipitates obtained were directly analyzed by graphite-furnace atomic
      absorption spectrometry (GFAAS) using the Ni-APDC complex solid-sampling
      technique. The coprecipitation conditions used for the trace amounts of arsenic
      and tin in natural water were investigated in detail. It was found that arsenic
      and tin at sub-ng mL(-1) levels were both coprecipitated quantitatively by
      Ni(PDC)2 in the pH range 2-3. The concentration factors by coprecipitation
      reached approximately 40,000 when 2 mg nickel was added as a carrier element to
      500 mL of the water sample. The proposed method has been applied to the
      determination of trace amounts of arsenic and tin in river water and seawater
      reference materials, and the detection limits for arsenic and tin, which were
      calculated from three times of the standard deviation of the procedural blanks,
      are 0.02 ng mL(-1) and 0.04 ng mL(-1), respectively, for 500-mL volumes of water
      sample.

PMID- 11569866
TI  - Speciation studies by capillary electrophoresis--distribution of rhodium(III)
      complexed forms in acidic media.
AB  - The feasibility of capillary electrophoresis for distinguishing between the
      rhodium(III) species occurring in different acidic environments has been
      demonstrated. The separation was optimum under acidic electrolyte conditions in
      which the complexed Rh species were at their most stable and the electroosmotic
      flow approached zero, thereby aiding resolution. Identification of the forms of
      Rh and estimation of their relative equilibrium content were accomplished by use
      of a diode-array detector. The distribution of the metal complexes was highly
      dependent on the nature and concentration of the acid and the age of the rhodium
      stock solutions. On dilution Rh(III) tends to be readily hydrolyzed, giving rise
      to a wider variety (and a varied distribution) of complexed forms. In 0.1 mol L(
      1) HCl, four differently charged chloro complexes--RhCl4(H2O)2-, RhCl3(OH)(H2O)2
      , RhCl3(H2O)3, and RhCl2(H2O)4+--were separated and identified. When a stock
      solution in 11 mol L(-1) HCl was run, Rh produced a major peak ascribed to
      RhCl6(3-) and two slowly migrating peaks from ions in which one or two of the
      chloride ligands were probably replaced by water and hydroxyl ion, as a result of
      hydrolysis. The aquatic cationic species were found to be predominant in HClO4
      and HNO3 solutions, whereas only negatively charged forms of Rh(III) occurred in
      sulfuric acid. This speciation information opens also new possibilities of
      assessing the catalytic activity of Rh in kinetic reactions.

PMID- 11569867
TI  - Simultaneous determination of butyltin and phenyltin species in sediments using
      ultrasound-assisted leaching.
AB  - A fast and simple procedure is presented for the simultaneous leaching of butyl
      (mono, di and tributyl) and phenyl organotin species from sediment samples.
      Leached compounds are further ethylated with sodium tetraethylborate in aqueous
      medium, and analyzed by gas chromatography. After testing the stability of
      triphenyltin under different extraction conditions, ultrasound-assisted leaching
      at room temperature in the presence of acetic acid was been proposed as an
      extraction procedure compatible with the simultaneous determination of phenyl-
      and butyltin compounds in sediments. Recoveries between 70 and 90% were obtained
      for phenyl species in spiked samples prepared in the laboratory. Results for
      butyltin species were validated by use of the reference material PACS-2.
      Quantification limits, using GC-MIP-AES as measurement technique, were
      approximately 5-10 ng g(-1). Precision in the consecutive analysis of three
      sediment samples varied between 3 and 10%.

PMID- 11569868
TI  - Study of an Au colloid self-assembled electrode and its application to the
      determination of carbon monoxide.
AB  - A novel electrochemical sensor has been developed for the detection of carbon
      monoxide. The chemically modified electrode, prepared by reaction of cysteine and
      then an Au colloid of size approximately 15 nm with a platinum microelectrode,
      has excellent catalytic activity toward carbon monoxide, with an oxidation
      potential of +600 mV relative to the Ag/AgCl electrode. The CO gas sensor is
      based on an Au colloid self-assembled modified electrode as working electrode, an
      Ag/AgCl electrode as reference electrode, a Pt electrode as counter electrode,
      and a porous film which is in direct contact with the gas-containing atmosphere.
      The effects on the determination of CO of different internal electrolyte
      solutions of perchloric acid, hydrochloric acid, sulfuric acid, nitric acid, and
      phosphate buffer of different concentrations were also studied. The sensor is
      characterized by a short response time and highly reproducible detection of CO.
      This sensor can be used in the field of environmental monitoring and control.

PMID- 11569869
TI  - Towards an understanding of solvent extraction--electroanalytical
      characterization of chloride-leaching solutions.
AB  - Solvent extraction has been employed to purify media simulating chloride-leaching
      solutions resulting from complex sulfide concentrate processing, and cyclic
      voltammetry (CV) has been chosen to characterize those hydrometallurgical aqueous
      phases. The possibilities of the CV technique were investigated by the evaluation
      of the adequacy of a specific organic extractant, triisobutylphosphine sulfide,
      aimed to efficiently and selectively extract silver from a complex chloride
      medium, additionally containing tenfold to 40-fold molar concentrations of iron,
      copper and lead. The influence of the oxidation state of the metallic ions
      present in the feed solution, namely Cu(II) and Cu(I), is considered. The
      possibilities of CV analysis for the characterization of stripping solutions are
      also illustrated.

PMID- 11569870
TI  - Characterization of ligand sites on natural sediment particles.
AB  - Organic and inorganic ligand sites on sediment particles were alkalimetrically
      titrated using a glass electrode as indicating device. Data obtained for
      suspensions containing known masses of sediment were used to calculate the
      concentration of surface ligand sites and their stability constants for complex
      formation with proton and copper(II) ion. The relationship between the
      concentration of ligand sites and the concentrations of metals (Cd, Cr, Cu, Fe,
      Mn, Pb, and Zn) and of C, N, and S was used to try to discriminate between the
      contributions of organic and inorganic components to the total ligand capacity of
      the sediment. The reliability of the chemical model deduced from potentiometric
      data was checked by comparing calculated values for aqueous copper(II) as a
      function of pH with values experimentally determined via atomic absorption
      spectrometry. The procedure proposed might contribute to the modeling of sediment
      contaminant interaction, providing information on the nature of the ligands
      involved.

PMID- 11569871
TI  - Membrane-controlled reagent-delivery systems--a new approach for the continuous
      production of reagent and standard solutions.
AB  - A new simple and robust system for the production of standard solutions, based on
      the mass-transfer of analytes through membranes, is described. The device
      consists of a cone-shaped reservoir vessel, filled with a concentrated solution
      of the analyte and separated from a liquid acceptor stream by a membrane. Mass
      flow from donor to acceptor solution is controlled by the mass-transfer-affecting
      properties of the active membrane area, which is determined by the hole in a
      template (diameter 0.8 mm) placed between the membrane and the acceptor-channel.
      Using nitrate as model analyte and a track-etched membrane filter (pore size 0.1
      microm) dilution factors up to 2,400,000 with long-term reproducible accuracy of
      < 2% have been achieved. Adjustment of a requested concentration is possible by
      varying either the flow rate of the acceptor stream or the concentration of the
      reservoir solution.

PMID- 11569872
TI  - Investigation of infrared calibration methods for application to the study of
      methyl methacrylate polymerization.
AB  - Infrared spectroscopy has been used to monitor the polymerization of methyl
      methacrylate. Concentrations of methyl methacrylate in the reaction mixture were
      determined by use of three calibration methods. Classical quantitative analysis
      was used to measure the height of the stretching vibration bands of the vinyl
      group at 1639 cm(-1). A calibration procedure using the considerably higher
      intensity of the C = O stretching vibration band of the carbonyl ester group at
      1725 cm(-1) seemed useful only for high concentrations of methyl methacrylate,
      i.e. at the beginning of reaction, because this band overlaps that of poly(methyl
      methacrylate). Use of second-derivative spectra and measuring their values at
      1725 cm(-1) enabled estimation of ten times lower concentrations of methyl
      methacrylate the calibration using the band from the vinyl group.

PMID- 11569873
TI  - In-situ separation of chromium(III) and chromium(VI) and sequential ETV-ICP-AES
      determination using acetylacetone and PTFE as chemical modifiers.
AB  - Electrothermal vaporization-inductively coupled plasma-atomic emission
      spectrometry (ETV-ICP-ES) has been used for the sequential determination of
      Cr(III) and Cr(VI). The method is based on the difference between the chelate
      reactions of the two Cr species and acetylacetone. Cr(III) chelate was separated
      from Cr(VI) and determined with use of acetylacetone as chemical modifier. The
      retained Cr(VI) in graphite tube was analyzed subsequently, after addition of
      polytetrafluoroethylene (PTFE) as chemical modifier. The different factors
      affecting the vaporization behavior of Cr(III) acetylacetonate were investigated
      in detail. The detection limits for Cr (III) and Cr(VI) were 0.56 and 1.4 ng mL(
      1), respectively, and relative standard deviations for 0.1 microg mL(-1) Cr(III)
      and 0.1 microg mL(-1) Cr(VI) were 2.5% (n = 6) and 4.8% (n = 6), respectively.
      The linear ranges of the calibration curve for both Cr(IIl) and Cr(VI) covered
      three orders of magnitude. The proposed method was used to analyze water samples
      with satisfactory results.

PMID- 11569874
TI  - Use of chelating resins and inductively coupled plasma mass spectrometry for
      simultaneous determination of trace and major elements in small volumes of saline
      water samples.
AB  - For some saline environments (e.g. deeply percolating groundwater, interstitial
      water in marine sediments, water sample collected after several steps of
      fractionation) the volume of water sample available is limited. A technique is
      presented which enables simultaneous determination of major and trace elements
      after preconcentration of only 60 mL sample on chelating resins. Chelex-100 and
      Chelamine were used for the preconcentration of trace elements (Cd, Cu, Pb, Zn,
      Sc) and rare earth elements (La, Ce, Nd, Yb) from saline water before their
      measurement by inductively coupled plasma mass spectrometry. Retention of the
      major elements (Na, Ca, Mg) by the Chelamine resin was lower than by Chelex; this
      enabled their direct measurement in the solution after passage through the resin
      column. For trace metal recoveries both resins yield the same mass balance. Only
      Chelex resin enabled the quantitative recovery of rare earth elements. The major
      elements, trace metals and rare earth elements cannot be measured after passage
      through one resin only. The protocol proposes the initial use of Chelamine for
      measurement of trace and major elements and then passage the same sample through
      the Chelex resin for determination of the rare earth elements. The detection
      limit ranged from 1 to 12 pg mL(-1). At concentrations of 1 ng mL(-1) of trace
      metals and REE spiked in coastal water the precision for 10 replicates was in the
      range of 0.3-3.4% (RSD). The accuracy of the method was demonstrated by analyzing
      two standard reference waters, SLRS-3 and CASS-3.

PMID- 11569875
TI  - Pressurized-fluid extraction (PFE) of chlorinated paraffins from the
      biodegradable fraction of source-separated household waste.
AB  - A method is presented in which pressurized-fluid extraction (PFE) is used for the
      extraction of chlorinated paraffins (CP) from the biodegradable fraction of
      source-separated household waste. The conditions that were optimized for high
      recovery in the extraction procedure were extraction time, temperature, and the
      use of different solvents and different sample particle sizes, Recoveries of CP
      from fortified household waste material were over 90%, with only few
      interferences when cyclohexane was used as solvent. Extraction yields from
      contaminated samples containing CP were further compared with recoveries obtained
      by use of Soxtec extraction. The results showed that PFE is a rapid, low-solvent
      consuming technique, giving high yields.

PMID- 11569876
TI  - Simultaneous determination of composition of human urinary calculi by use of
      artificial neural networks.
AB  - A new chemometric method, which uses artificial neural networks (ANN), is
      presented for determination of the composition of urinary calculi. The selected
      constituents were whewellite, weddellite, and uric acid from which approximately
      40% of the urinary calculi obtained from Macedonia patients are composed. The
      results for the synthetic mixtures were better then those obtained by partial
      least squares (PLS) regression or by the principal component regression (PCR),
      because neural networks have better prediction capacity. The generalization
      abilities of the optimized neural networks were checked using the standard
      addition method on carefully selected real natural samples.

PMID- 11569877
TI  - Fluorine determination in human and animal bones by particle-induced gamma-ray
      emission.
AB  - Fluorine was determined in the iliac crest bones of patients and in ribs
      collected from post-mortem investigations by particle-induced gamma-ray emission
      based on the 19F(p,p'gamma)19F reaction, using 2.0/2.5 MeV protons. The results
      indicate that for 68% of the human samples the F concentration is in the range
      500-1999 microg g(-1). For comparison purposes fluorine was also determined in
      some animal bones; in some animal tissues lateral profiles of fluorine were
      measured.

PMID- 11569878
TI  - Application of a novel micro-injector in the determination of indole derivatives
      in the rat pineal gland by capillary electrophoresis with electrochemical
      detection.
AB  - A novel micro-injector has been fabricated for capillary electrophoresis (CE). It
      was successfully used for the determination of some indole derivatives for
      example melatonin (MT), serotonin (5-HT), tryptophan (Trp), and 5-hydroxy
      tryptophane (5-HTrp) in the rat pineal gland by capillary electrophoresis with
      electrochemical detection (CE-EC). CE was performed in 0.20 mol L(-1) phosphate
      buffer (pH 8.0). The compounds investigated can be well separated and detected
      within 15 min. The working electrode used was a 300-microm diameter carbon
      electrode positioned opposite the outlet of the capillary. The relationship
      between peak current and analyte concentration was highly linear in the range
      from 0.10 to 500 micromol L(-1); detection limits (S/N = 3) were 0.03-0.13
      micromol L(-1). The proposed method has been successfully used to analyze real
      biological samples.

PMID- 11569879
TI  - Estimation of the minimum uncertainty of DNA concentration in a genetically
      modified maize sample candidate certified reference material.
AB  - Homogeneity testing and the determination of minimum sample mass are an important
      part of the certification of reference materials. The smallest theoretically
      achievable uncertainty of certified concentration values is limited by the
      concentration distribution of analyte in the different particle size fractions of
      powdered biological samples. This might be of special importance if the reference
      material is prepared by dry mixing, a dilution technique which is used for the
      production of the new and third generation of genetically modified (GMO) plant
      certified reference materials. For the production of dry mixed PMON 810 maize
      reference material a computer program was developed to calculate the
      theoretically smallest uncertainty for a selected sample intake. This model was
      used to compare three differently milled maize samples, and the effect of
      dilution on the uncertainty of the DNA content of GMO maize was estimated as
      well. In the case of a 50-mg sample mass the lowest achievable standard deviation
      was 2% for the sample containing 0.1% GMO and the minimum deviation was less than
      0.5% for the sample containing 5% GMO.

PMID- 11569880
TI  - Determination of antifouling pesticides and their degradation products in marine
      sediments by means of ultrasonic extraction and HPLC-APCI-MS.
AB  - A method has been developed for the simultaneous determination of antifouling
      pesticides and some of their degradation products, e.g. dichlofluanid, diuron,
      demethyldiuron, 1-(3,4-dichlorophenyl)urea, sea-nine, Irgarol 1051 and one of its
      metabolites (2-methylthio-4-tert-butylamino-s-triazine) in marine sediments. The
      determination of these compounds in sediment samples was performed by means of
      methanolic ultrasonic extraction then clean-up on an Isolute ENV+ solid phase
      extraction (SPE) cartridge. The resulting extract was then analyzed by reversed
      phase high-performance liquid chromatography coupled with atmospheric-pressure
      chemical-ionization mass spectrometry in negative and positive ion modes (HPLC
      APCI-MS). Recovery ranged from 54-109% for the antifouling agents and their
      degradation products. The determination limits for the different compounds varied
      between 0.2 and 1.6 microg kg(-1) dry sediment. The analytical procedure was
      successfully applied to the determination of these pesticides and their
      degradation products in marine sediment samples from different marinas of the
      Catalan coast. The compounds detected were: diuron, dichlofluanid,
      demethyldiuron, sea-nine, and Irgarol 1051. The highest concentrations were those
      of diuron and Irgarol 1051--136 and 88 microg kg(-1), respectively.

PMID- 11569881
TI  - Determination of penconazole on personal protection equipment after field
      applications.
AB  - A simple analytical method, validated in-house and intra-laboratory, has been
      developed for the determination of penconazole on personal protection equipment
      (PPE) used by operators during field applications of Topas 20EW. The analytical
      determination of penconazole was performed by GC-ECD. Sample preparation was
      based on a liquid extraction procedure. The possible effect of different personal
      protection equipment matrices on the analytical determination of penconazole was
      studied and evaluated with regression analysis. No evidence of significant (at
      95% CI level) effect was observed at several fortification levels. The percentage
      recovery of penconazole from the different PPE was in the range 59-100% with
      adequate correlation with the level of fortification (r2>0.99). The RSD% was in
      the range of 1-15% and the LOD and LOQ for penconazole were 0.84 and 2.5 ng mL(
      1), respectively.

PMID- 11569882
TI  - Comparison of the chiral resolution of econazole, miconazole, and sulconazole by
      HPLC using normal-phase amylose CSPs.
AB  - Resolution of the enantiomers of (+/-)-econazole, (+/-)-miconazole, and (+/-)
      sulconazole has been achieved on different normal-phase chiral amylose columns,
      Chi-ralpak AD, AS, and AR. The mobile phase used was hexane-2-propanol
      diethylamine, 400:99:1 (v/v). The flow rates of the mobile phase used were 0.50
      and 1.00 mL min(-1). The alpha values for the resolved enantiomers of econazole,
      miconazole, and sulconazole on the chiral phases were in the range 1.63 to 1.04;
      the Rs values varied from 5.68 to 0.32.

PMID- 11569883
TI  - Covalent modification of glassy carbon electrodes with glycine for voltammetric
      separation of dopamine and ascorbic acid.
AB  - Glycine was covalently grafted on to a glassy carbon electrode (GCE) by amine
      cation radical formation in electrooxidation of the amino-containing compound. X
      ray photoelectron spectroscopy (XPS) and cyclic voltammetry proved the
      immobilization of glycine on the GCE. The modified electrode reduced the
      overpotentials of dopamine (DA) and ascorbic acid (AA) by approximately 0.15 V
      and 0.23 V, respectively, and resolved the overlapping voltammetric response of
      DA and AA into two well-defined voltammetric peaks in cyclic voltammetry (CV) or
      differential pulse voltammetry (DPV), unlike the unmodified GCE; this can be used
      for the simultaneous determination of these species in a mixture. The
      differential pulse peak current was linearly dependent on DA and AA concentration
      in the range 5 x 10(-6)-8 x 10(-4) mol L(-1) and 6 x 10(-5)-4 x 10(-3) mol L(-1),
      with correlation coefficients of 0.996 and 0.994, respectively. The detection
      limits (3delta) for DA and AA were 1.8 x 10(-6) mol L(-1) and 2.1 x 10(-5) mol L(
      1), respectively. The modified electrode is very sensitive, selective and stable,
      and has been applied to the determination of DA and AA simultaneously in samples
      with satisfactory results.

PMID- 11569884
TI  - Electrochemical behavior and voltammetric determination of the herbicide
      metribuzin at mercury electrodes.
AB  - The electrochemical behavior of the herbicide metribuzin (4-amino-6-tert-butyl
      4,5-dihydro-3-methylthio-1,2,4-triazin-5-one) at mercury electrodes was studied
      in aqueous solutions by direct current (DC) and tast polarography, differential
      pulse (DPV) and cyclic voltammetry (CV), and controlled-potential coulometry. The
      electrolysis products were separated and identified by chromatographic techniques
      combined with mass spectrometric detection. The reduction process in acid media
      includes two irreversible steps. In the first four-electron step the N-NH2 and
      the 1,6-azomethine bonds are reduced. The second step leads to the formation of 5
      tert-butyl-2,3,4,5-tetrahydroimidazol-4-one at the mercury-pool electrode. The
      first reduction step combined with adsorptive accumulation of the herbicide
      molecule at the mercury electrode surface was used for its determination by
      differential pulse adsorptive stripping voltammetry (DPAdSV). Calibration curves
      were linear in the range 1-30 microg L(-1) with a detection limit of 0.27 microg
      L(-1) (1 nmol L(-1)) under the conditions used (buffer pH 4.5, Eacc = -0.45 V
      relative to Ag/AgCl and tacc = 10 s). Preconcentration on solid-phase extraction
      columns (SPE-phenyl) was used for the determination of very small amounts of
      metribuzin in river water samples. Recovery was approximately 97%. The
      reproducibility of the analytical procedure including SPE treatment and DPV
      determination was expressed as relative standard deviations of 2.53 and 3.66% for
      2 and 6 microg L(-1) metribuzin, respectively.

PMID- 11569885
TI  - Microwave-assisted extraction of polycyclic aromatic compounds from coal.
AB  - Microwave-assisted extraction (MAE) of polycyclic aromatic compounds (PACs) from
      coal is shown to give the same pattern of compounds as Soxhlet extraction. MAE
      requires only 10 mL solvent and 10 min extraction time whereas Soxhlet uses 200
      mL and takes 24 h. Although the yields were lower, dichloromethane (DCM) was
      preferred to pyridine, N-methyl-2-pyrrolidone (NMP), and NMP with CS2 because the
      pattern of the PACs is shown to be independent of solvent and DCM is a much more
      convenient solvent to work with.

PMID- 11569886
TI  - Micellar electrokinetic capillary chromatography as an alternative method for the
      determination of dexamethasone, trimethoprim, and polymyxin B.
AB  - A micellar electrokinetic capillary chromatographic method is presented which
      enables quantification of dexamethasone, polymyxin B and trimethoprim in
      synthetic mixtures and pharmaceutical products. Separation was carried out at 25
      degrees C and 30 kV, with 10 mmol L(-1) borate-phosphate buffer adjusted to pH 8
      as electrolyte, with 50 mmol L(-1) sodium dodecyl sulfate. Under these conditions
      separations were performed in 10 min. The limits of detection and quantification
      were approximately 2 mg L(-1) for each component, except for polymyxin B. The
      method was applied to different commercial formulations.

PMID- 11569887
TI  - Methodologic guidelines for the design of high-dose chemotherapy regimens.
AB  - PURPOSE: The objective of this report is to review the research methods that have
      been used in the design, analysis, and reporting of Phase I dose-escalation
      studies of high-dose chemotherapy (HDCT) with bone marrow or stem cell support
      and to propose new guidelines for such studies that incorporate emerging
      principles of pharmacology, toxicity assessment, statistical design, and long
      term follow-up. METHODS: We performed a search of original, English-language,
      peer-reviewed full-length reports of HDCT (with or without radiotherapy) and
      unmanipulated hematopoietic precursor support (autologous bone marrow or stem
      cells or allogeneic bone marrow) in which one or more drug doses were escalated
      to identify dose-limiting toxicities needed for the design of subsequent Phase II
      trials. We reviewed the design, execution, analysis, and reporting of these
      trials to develop a coherent set of guidelines for the initiation of new HDCT
      regimens. The primary elements included in our analysis were the technique of
      dose escalation, the choice and application of toxicity grading scale, and the
      pharmacologic correlates of dose escalation. We also evaluated the methods
      employed to define dose-limiting toxicities and to select the maximum tolerated
      dose and the dose recommended for further study. We then examined whether
      subsequent Phase II trials based on these definitions corroborated the findings
      from the prior Phase I studies and summarized the findings from pharmacologic
      analyses that were reported from a subset of these investigations. RESULTS:
      Thirty-five reports met the criteria for our literature review. Two standard
      methods of dose escalation (fixed increments or modified Fibonacci increments)
      were described in detail and were employed in the majority (30/35) of the
      studies. In 5 studies, the details of dose escalation were either not provided or
      not adequately referenced. There was marked heterogeneity among toxicity grading
      methods; scales used included the National Cancer Institute Common Toxicity
      Criteria (or similar scales such as the United States cooperative group or World
      Health Organization scales) as well as substantially modified versions of those
      instruments. Wide variations in the methods used to identify dose-limiting
      toxicities were observed. Statistical considerations, applied to the
      identification of the maximum tolerated or Phase II recommended dose, were
      similarly heterogeneous. Phase II trial designs varied from a simple expansion of
      the Phase I trial to separate, formally conducted studies. Nine Phase I trials
      featured pharmacologic analyses, and these ranged from simple pharmacokinetic
      evaluations to more complex analyses of the relationship between drug dose and
      the molecular targets of drug action. CONCLUSIONS: Phase I clinical trials in the
      HDCT setting have been designed, analyzed, and reported using heterogeneous
      methods that limited their application to Phase II and II investigations.
      Moreover, correlative pharmacologic analyses have not been routinely undertaken
      during this critical Phase I stage. We propose guidelines for the design of new
      Phase I studies of HDCT based on 4 essential elements: (1) rational preclinical
      and clinical pharmacologic foundation for the regimen and for the agent selected
      for dose escalation; (2) incorporation of analytical pharmacology in the design
      and analysis of the regimen under investigation; (3) clear, prospective
      definitions of the dose- or exposure-limiting toxicities that can be
      distinguished from modality-dependent toxicities; selection of an appropriate
      toxicity grading scale, including an assessment of cumulative, delayed, and long
      term effects of HDCT, particularly when designing tandem or repetitive cycle
      regimens; and (4) statistical input into the design, execution, analysis,
      interpretation, and reporting of these studies.

PMID- 11569888
TI  - Engraftment syndrome in breast cancer patients after stem cell transplantation is
      associated with poor long-term survival.
AB  - An autoaggression graft-versus-host (GVHD)-like syndrome or engraftment syndrome
      (ES) presenting with skin rash, fever, and other clinical findings can accompany
      the early phase of engraftment after autologous peripheral blood stem cell
      (PBSC)/bone marrow (BM) transplantation. Because ES was suggested to be analogous
      to GVHD, we have investigated whether ES was associated with any graft-versus
      tumor effect that would affect disease progression and survival in breast cancer
      patients. Eighty-five consecutive patients who received BM/PBSC transplantation
      for breast cancer (stages II-IV) between July 1991 and July 1997 with minimum 2
      year follow-up were studied. Median follow-up time was 892 days (range, 106-2913
      days). Thirty-three patients (39%) developed ES. The incidence of
      relapse/progressive disease for the whole cohort was 61% and was similar in
      patients who developed ES compared with those who did not. However, there was an
      increased rate of mortality observed among the patients who had developed ES
      versus those who had not, although it was statistically not significant, (52%
      versus 31%, respectively; log rank, P = .08). Increased mortality rates due to
      disease progression were seen in all patients with ES regardless of their disease
      stage. In relapsed patients, median survival time after transplantation was 586
      days for those with ES versus 847 days for those without ES, and the mortality
      rate was 85% (17/20) versus 51% (16/31) (P = .008) for those with or without ES,
      respectively. Visceral (lung, liver, brain, adrenal) or multiple-site relapses
      were observed in 85% of patients with ES versus 52% without ES (P = .01). In
      conclusion, whereas there was no effect of ES on relapse rate, a surprisingly
      significant increase in disease-related mortality rates among relapsed breast
      cancer patients with ES was found. Thus, patients with ES should be considered
      for close follow-up and further therapy posttransplantation.

PMID- 11569889
TI  - Randomized open-label trial of dolasetron for the control of nausea and vomiting
      associated with high-dose chemotherapy with hematopoietic stem cell
      transplantation.
AB  - A prospective open-label trial was performed to compare the efficacy of
      dolasetron with that of ondansetron or granisetron (standard therapy) for
      prevention of nausea and vomiting associated with high-dose chemotherapy with or
      without total body irradiation followed by hematopoietic stem cell
      transplantation (HSCT). In a university teaching hospital setting, 62 patients
      were randomized to receive either dolasetron 100 mg daily or standard doses of
      ondansetron or granisetron. In addition to objective data such as number of
      episodes of emesis and quantity of rescue antiemetics required, 100 mm visual
      analogue scales were used to rate nausea, appetite, and changes in taste. A post
      hoc subgroup analysis was performed between groups of patients that were matched
      for conditioning regimens. Sixty-five percent of the dolasetron-treated patients
      and 87% of patients in the standard therapy group achieved a major or complete
      response (P < .05) based on emetic episodes and nausea score. Patients in the
      standard therapy group used fewer rescue antiemetics and also rated more
      favorably on selected questions of the visual analogue scale. No differences in
      safety parameters or adverse effects were reported. At doses prescribed in this
      study, dolasetron was less effective than granisetron or ondansetron in
      preventing nausea and vomiting associated with high-dose chemotherapy/total body
      irradiation followed by HSCT.

PMID- 11569890
TI  - The impact of external beam radiation therapy prior to autologous bone marrow
      transplantation in patients with non-Hodgkin's lymphoma.
AB  - External beam radiation therapy (XRT) is frequently used to treat refractory
      disease sites or consolidate remission in patients with relapsed non-Hodgkin's
      lymphoma (NHL) prior to autologous bone marrow transplantation (ABMT). We report
      the long-term outcome and toxicities associated with this therapy. We uniformly
      treated 552 patients with NHL with total body irradiation, high-dose
      chemotherapy, and anti-B-cell monoclonal antibody-purged ABMT. Of these patients,
      152 received XRT to the mediastinum, abdomen, or pelvis (n = 102) or other sites
      (n = 50) prior to ABMT. In this nonrandomized series, there was no difference in
      progression-free survival between patients treated with XRT and those not treated
      with XRT. For patients with indolent histology, there was no difference in
      overall survival between patients treated with XRT and those not treated with
      XRT. For patients with aggressive histology, the median overall survival time was
      64 months in the XRT patients and 79 months in the patients not treated with XRT
      (P= .09). The risk of acute transplantation-related deaths was not influenced by
      prior XRT (P = .68). Of patients who received XRT, 12.5% developed secondary
      myelodysplasia compared with 5.8% of patients not receiving XRT (P = .01).
      Patients receiving XRT to the mediastinum or axilla had a significantly higher
      risk of late respiratory death (P = .002). In conclusion, XRT allows refractory
      patients to become eligible for transplantation and experience a disease-free
      survival interval equivalent to that of patients who do not receive XRT. However,
      a higher incidence of non-relapse-associated deaths was observed in patients who
      received XRT. Future work should explore alternative conditioning strategies and
      altered timing of XRT, in an attempt to limit these late toxicities.

PMID- 11569892
TI  - Hereditary and acquired amyloid neuropathies.
AB  - Amyloid neuropathies occur in a context of hereditary (FAP) or acquired
      amyloidosis. They present usually as severe and progressive polyneuropathy and
      carry a poor prognosis. Most FAP are associated with endoneurial deposits of
      variant transthyretin (TTR) with substitution of one aminoacid and are secondary
      to a point mutation of the TTR gene. Portugal is the main endemic area of TTR
      FAP, secondary to point mutation of exon 2. However, around the world, 50 other
      TTR gene mutations have been recently reported, each one in few families. Genetic
      studies are useful for diagnosis of FAP in patients with a positive family
      history and for identification of the cause of seemingly sporadic cases. TTR gene
      analysis is also useful for genetic counselling including antenatal diagnosis in
      variants with early onset. Gel-solin-FAP are the second variety and present as a
      benign cranial and sensory polyneuropathy and affect essentially Finnish
      patients. Acquired amyloid neuropathy concerns only immunoglobulin light chain
      amyloidosis (AL) and are frequently associated with renal manifestations and
      monoclonal protein in serum or urine. Specific treatment of amyloid
      polyneuropathy varies with the variety of amyloidosis including liver
      transplantation in TTR-FAP, at the onset of the disease or chemotherapy for
      immunoglobulin light chain amyloidosis.

PMID- 11569891
TI  - T-Cell recovery in adults and children following umbilical cord blood
      transplantation.
AB  - T-cell reconstitution following allogeneic stem cell transplantation may involve
      thymic education of donor-derived precursors or peripheral expansion of mature T
      cells transferred in the graft. T cell-receptor excision circles (sjTRECs) are
      generated within the thymus and identify new thymic emigrants and those that have
      not divided. We measured quantitative and qualitative immunologic reconstitution
      and sjTREC levels in adult and pediatric recipients of umbilical cord blood
      transplants (UCBTs). sjTRECs were detected at normal levels in all children,
      starting 12 months after transplantation. sjTRECs were not detected until 18
      months after transplantation in adults, and then only at a 3-fold lower level
      than expected for age. We used complementarity-determining region 3 (CDR3)
      spectratyping to measure changes in T cell-receptor diversity occurring with
      restoration of thymic function. T-cell repertoires were skewed in adults and
      children at 12 to 18 months after transplantation but recovered to near-normal
      diversity at 2 to 3 years post-UCBT. T-cell repertoires appeared more diverse
      earlier in children (at 1 to 2 years post-UCBT) than in adults (at 3 to 4 years
      post-UCBT). We conclude that early T-cell recovery after UCBT occurs primarily
      through peripheral expansion of adoptively transferred donor T cells and results
      in skewing of the T-cell repertoire. The reappearance of sjTREC-containing cells
      after UCBT is associated with increasing numbers of phenotypicaly naive T cells,
      improved mitogen and recall antigen responses, and diversification of the T-cell
      repertoire. The delay in central T-cell recovery in adults relative to children
      may be due to differences in thymic function resulting from age-related atrophy,
      graft-versus-host disease, or the pharmacologic effects of prophylaxis and
      treatment of graft-versus-host disease.

PMID- 11569893
TI  - Disorders of single word processing.
AB  - In recent years, studies in the cognitive neuropsychology of language have helped
      in understanding the functional architecture of linguistic processes. It has been
      shown that recognizing, comprehending and producing a word entails the activation
      of a complex set of mechanisms, each of which can be selectively impaired as a
      consequence of brain damage. Investigations of aphasic subjects have demonstrated
      that the meaning, the pronunciation and the spelling of a word are represented
      independently, that category information plays a critical role in semantic
      organization, and that the mental vocabulary represents word class and
      morphological structure. These distinctions in the architecture of the lexical
      semantic system, in turn, have provided the basis for PET and fMRI studies of the
      neural correlates of single-word processing. These experiments, in agreement with
      recent neurophysiological investigations, suggest that cognitive/linguistic
      functions are likely to be represented in distributed neural networks often
      encompassing more than one lobe, rather than in individual, sharply demarcated
      neural structures.

PMID- 11569894
TI  - Randomized trial of 4-aminopyridine in patients with chronic incomplete spinal
      cord injury.
AB  - OBJECTIVE: To test the efficacy of 4-aminopyridine (4-AP) on functional status,
      walking speed and vibration perception in patients with chronic, incomplete
      spinal cord injury. METHODS: Twenty SCI patients were randomized in a trial with
      a double-blind, crossover design to receive four weeks of orally administered 4
      AP, followed by a two-week wash-out period and four weeks of placebo, or vice
      versa. The total daily dose of 4-AP during the four weeks of treatment was
      systematically increased to a maximum of 0.5 mg/kg body weight. Evaluation of
      (side-)effects took place at the beginning, after one week, and at the end of
      each four-week study period. RESULTS: No significant benefit was found on
      functional status (COOP-WONCA). A statistically significant treatment effect was
      found on the vibration perception threshold (VPT) in the left fingers, during the
      first study period. On average, patients receiving 4-AP treatment responded less
      favourably (mean increase in VPT of 0.29 (0.31) microm) than patients receiving
      placebo (mean decrease in VPT of 0.05 (0.35) microm) (p=0.04). Neither
      comfortable nor maximum walking speed altered significantly following 4-AP
      treatment. CONCLUSIONS: No statistically significant, functional benefit from 4
      AP was found for patients in the present study. Furthermore, no support was found
      for the possibility that an a priory selection of responsive patients would have
      yielded more favourable results.

PMID- 11569895
TI  - Silver stained isoelectrophoresis of tears and cerebrospinal fluid in multiple
      sclerosis.
AB  - Cerebrospinal fluid (CSF) analysis aids in the diagnosis of multiple sclerosis.
      However, this examination is invasive. The aim of this study was to assess the
      potentials of a new method of tears isoelectrophoresis (IEF). Silver staining of
      IEF was used to examined tears and CSF from 123 patients including 60 patients
      with multiple sclerosis (MS), 50 other neurological patients and 13 patients with
      inflammatory neurological diseases. Tears were collected on a Shirmer strip
      placed in one eye, avoiding reflex secretion. This method of IEF with silver
      staining allowed the detection of oligoclonal bands in tears that were truly
      immunoglobulin G on immunofixation. The concordance rate between tears and CSF
      was 83%, meaning that CSF provided no more information than tears analysis in 83%
      of cases. Sensitivity in tears (72%) and CSF (75%) was very close as was
      specificity (respectively 84 % and 86 %). High concordance between tears and CSF
      is the first step in developing a non invasive test which could replace lumbar
      puncture, particularly when this procedure is not fearalele or is refused by the
      patient.

PMID- 11569896
TI  - Auditory laterality and attentional deficits after thalamic haemorrhage.
AB  - Thalamic lesions have been shown to produce severe cognitive deficits involving
      language and memory. A majority of the studies have reported cognitive deficits
      after lesions in the anterior and dorsomedial thalamic nuclei. We report five
      case studies of effects on language processing after postero-dorsal thalamic
      haemorrhages. Four of the patients had lesions on the right side, and one patient
      had a lesion on the left side. Effects on language processing were investigated
      with the dichotic listening test with consonant-vowel syllables. This test, in
      which conflicting auditory stimuli are presented simultaneously to the two ears,
      has been used to probe differences in language processing in the left and right
      hemispheres. The four patients with right-sided lesions reported almost none of
      the syllables presented to the left ear, and were unable to modify this massive
      right ear advantage by directing attention to the left or right ear. The patient
      with a left-sided lesion showed a weaker left ear advantage, and was able to
      modify his responses by shifting attention, to an extent similar to that of
      healthy reference individuals. When tested with monaural stimulus presentation,
      the scores of all patients rose to almost 100% correct for each ear. The pattern
      of effects with dichotic stimuli under different instructional conditions cannot
      be accounted for in purely structural terms, and indicates that lesions in the
      posterior part of the thalamus, including the pulvinar nucleus and medial
      geniculate body, produce deficits not only in processing of complex auditory
      stimuli but also in the allocation of attention to input from one ear or the
      other.

PMID- 11569897
TI  - Echogenicity of the substantia nigra in Parkinson's disease and its relation to
      clinical findings.
AB  - Recently an increased echogenicity of the substantia nigra (SN) in patients with
      Parkinson's disease (PD) was demonstrated by transcranial ultrasound (TCS). In
      this study we set out to compare SN echogenicitiy with disease characteristics
      (time of onset, duration, toxin exposure) in a large patients sample. Patients'
      history and exposure to toxins were recorded from 112 PD patients who underwent a
      thorough neurological examination including assessment of disease stage according
      to Hoehn and Yahr and CURS (Columbia University Rating Scale). Personality was
      assessed according to the Freiburg Personality Inventory. In all patients the
      area of SN echogenicity was encircled and measured by TCS. All except 9 patients
      had hyperechogenic SN areas exceeding the mean plus standard deviation values of
      an age matched control group (0.19 cm2). The age of disease onset was lower in
      patients who displayed an area of SN echogenicity above this value. The area of
      SN echogenicity was larger contralateral to the side with more severe symptoms.
      None of the other characteristics correlated with ultrasound findings. We
      conclude that SN hyperechogenicity is a typical finding in PD. The cause of
      hyperechogenicity is so far unknown. Investigation of the underlying reason might
      disclose a pathogenic factor in PD.

PMID- 11569898
TI  - Unaltered apoptotic behaviour of mononuclear cells from patients with sporadic
      Creutzfeldt-Jakob disease.
AB  - Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible spongiform
      encephalopathies. It is suspected that a pathologically altered form of the prion
      protein (PrPSc) is the decisive trigger of the disease. Data from animal
      experiments suggest an involvement of the lymphatic system in the intracorporal
      transport of PrPSc. However, it has not so far been possible to detect PrPSc on
      mononuclear cells (MNCs) either in the sporadic form of CJD or in the new variant
      of CJD (vCJD). In order to determine a possible alteration of MNCs in CJD, we
      investigated the natural and induced apoptotic behaviour of these cells. MNCs
      from 19 patients with sporadic CJD and from 20 patients with other neurological
      disorders were used. The cells were analysed by fluorescence cytometry with and
      without apoptosis induction by xanthine oxidase and hypoxanthine. The apoptosis
      rate was quantified using the stain 7-amino-actinomycin D (7-AAD). In the
      morphological investigation of the cells before apoptosis induction, there were
      no significant differences between the groups with regard to cell size and
      granularity of the MNCs. After apoptosis induction, the typical significant
      decrease in cell size and increase in granularity of the cells occurred in both
      groups. Significant differences between the patient populations were not found.
      For the first time, our investigation has demonstrated that a functional
      impairment of MNCs with regard to their apoptotic behaviour does not occur in
      sporadic CJD. It remains open to question whether this mechanism plays an
      important role in forms of transmissible encephalopathy other than sporadic CJD,
      especially after oral transmission.

PMID- 11569899
TI  - Deep brain stimulation in the treatment of severe dystonia.
AB  - A retrospective study of a consecutive series of 19 patients with medically
      intractable dystonia treated with uni- or bilateral deep brain stimulation (DBS)
      is reported. A minimal follow-up of 6 months was available, up to eleven years in
      one patient. The first twelve consecutive patients (4 with primary and 8 with
      secondary dystonia) were treated with chronic stimulation of the posterior part
      of the ventrolateral thalamic nucleus (VLp). In this group global functional
      outcome was improved in 8 patients, although dystonia movement and disability
      scale scores did not show significant improvement. Of the 12 patients treated
      first by VLp DBS, three (1 primary and 2 secondary dystonia) underwent pallidal
      (GPi) DBS after the VLp DBS failed to improve their symptoms. The last seven
      consecutive patients (5 primary and 2 secondary dystonia) were treated directly
      with GPi DBS. Extracranial infection prevented chronic GPi DBS in one patient. In
      another GPi patient, preliminary negative tests with the electrodes discouraged
      implantation of the stimulators, and the patient was not treated with chronic
      DBS. In the remaining group of eight patients including those previously treated
      with VLp DBS, chronic GPi DBS resulted in a significant improvement in the
      dystonia movement scale and disability scores. Although this is a retrospective
      study dealing with dystonia of heterogeneous etiology, the results strongly
      suggest that GPi DBS has a better outcome than VLp DBS.

PMID- 11569900
TI  - Activated protein C resistance and acute ischaemic stroke: relation to stroke
      causation and age.
AB  - OBJECTIVES: Resistance to activated protein C (APC) is the most frequent cause of
      thrombophilia and a well known risk factor for deep and cerebral vein thrombosis.
      Its causative role in ischaemic stroke is still a matter of debate. We undertook
      this study to determine the prevalence of APC-resistance in a cohort of
      consecutive patients with acute ischaemic stroke, especially with respect to
      patients' age and the underlying stroke causation. MATERIALS AND METHODS: 489
      patients with proven ischaemic stroke were included in this study. Subtypes of
      stroke were classified according to the TOAST criteria, i. e. large artery
      artherosclerosis (LAA), small vessel occlusion (SVO), cardioembolism (CE), stroke
      of other etiology (SOE), and stroke of undetermined etiology (SUE). APC
      resistance was determined with a functional method with high sensitivity and
      specificity for the factor V Leiden mutation. The results were compared with the
      prevalence of APC-resistance in healthy volunteers, all born in the same area.
      RESULTS: APC-resistance was found in 24 of 489 patients (4.9 %) and in 6 of the
      112 (5.4 %) control subjects. In the stroke patients, APC-resistance was
      distributed as follows: LAA 6.5 % (9/138), SVO 3,9 % (4/104), CE 6.7 % (7/104),
      SOE 3.6 % (1/28), SUE 2.6 % (3/115). Prevalence of APC-resistance was not
      significantly different between young stroke patients (6-45 years) and older
      patients (7.7 % [5/65] versus 4.5 % [19/424]). CONCLUSIONS: Prevalence of APC
      resistance is not increased in patients with ischaemic stroke. Additionally, no
      significant differences in the prevalence of APC-resistance are evident within
      the various stroke subtypes.

PMID- 11569901
TI  - Copper deficiency-associated myelopathy in a 46-year-old woman.

PMID- 11569902
TI  - Human swayback disease: expanding the spectrum of diseases associated with
      abnormal copper metabolism.

PMID- 11569903
TI  - Ilioinguinal neuralgia complicating percutaneous renal biopsy.

PMID- 11569904
TI  - Dopaminergic pathways involvement in Kennedy's disease: neurophysiological and.

PMID- 11569905
TI  - Mycophenolate-mofetil in the treatment of refractory multiple sclerosis.

PMID- 11569906
TI  - Spontaneous resolution of a tectal plate cyst.

PMID- 11569907
TI  - Clinical and genetic analysis of an Italian family with Machado-Joseph disease.

PMID- 11569908
TI  - Guillain-Barre syndrome mimicking botulism.

PMID- 11569909
TI  - Reversible blindness after bilateral occipital abscesses.

PMID- 11569910
TI  - Deep brain stimulation holidays in essential tremor.

PMID- 11569911
TI  - Object categorisation in vision is biased by centre-periphery organisation.

PMID- 11569912
TI  - As others see us: accomplishments over 25 years reflect the symbiotic link
      between biology and chemistry.

PMID- 11569913
TI  - Unraveling the role of mitochondria during oxidative stress in plants.
AB  - The sedentary habit of plants means that they must stand and fight environmental
      stresses that their mobile animal cousins can avoid. A range of these abiotic
      stresses initiate the production in plant cells of reactive oxygen and nitrogen
      species that ultimately lead to oxidative damage affecting the yield and quality
      of plant products. A complex network of enzyme systems, producing and quenching
      these reactive species operate in different organelles. It is the integration of
      these compartmented defense systems that coordinates an effective response to the
      various stresses. Future attempts to improve plant growth or yield must consider
      the complexity of inter-organelle signaling and protein targeting if they are to
      be successful in producing plants with resistance to a broad range of stresses.
      Here we highlight the role of pre-oxidant, antioxidant, and post-oxidant defense
      systems in plant mitochondria and the potential role of proteins targeted to both
      mitochondria and chloroplasts, in an integrated defense against oxidative damage
      in plants.

PMID- 11569914
TI  - In vivo function of a differentiation inhibitor, Id2.
AB  - Cell differentiation is an essential process for the development of various cell
      types that constitute multicellular organisms. During development, the large
      family of factors bearing a helix-loop-helix (HLH) motif participates profoundly
      in this process and these factors serve as good experimental tools for
      investigating mechanisms underlying tissue-specific differentiation. The HLH
      family includes both positive and negative regulators of cell differentiation:
      basic HLH (bHLH)-type transcription factors and Id proteins, respectively.
      Following an exciting decade focusing on bHLH factors, advances achieved in
      studies of the inhibitory factors in the last couple of years have placed them in
      the front line of the research on differentiation and proliferation control.
      Here, we present and discuss recent results obtained using Id2-deficient mice,
      which manifest intriguing phenotypes in various systems.

PMID- 11569915
TI  - Evolutionary aspects of calmodulin.
AB  - Calmodulin (CaM) is a major cellular sensor of calcium signaling, interacts with
      numerous proteins associated with cellular second messenger systems (e.g., cyclic
      AMP, nitric oxide), and is associated with neurosecretory activity. An identical
      CaM protein consisting of four helix-loop-helix regions that arose by gene
      duplication is encoded by three nonallelic mammalian genes that are some of the
      most highly conserved genes known. Differential tissue and cellular expression of
      each CaM suggest unique functions that promote strong selective preservation of
      these replicate, yet distinct, CaM genes in mammals. Each gene displays the same
      exon-intron arrangement but is characterized by distinct promoter elements and by
      unique 5'- and 3'-untranslated regions that are highly conserved among human,
      rat, and mouse. These distinct untranslated regions may permit regulation of CaM
      levels at discrete cellular sites during differentiation and in highly
      specialized cell types such as neurons.

PMID- 11569916
TI  - The peroxisome in oxidative stress.
AB  - Peroxisomes are one of the main sites in the cell where oxygen free radicals are
      both generated and scavenged. The balance between these two processes is believed
      to be of great importance for proper functioning of cells and has been implicated
      in aging and carcinogenesis. We will give an overview of the peroxisomal
      processes involved in the oxygen radical homeostasis and its implications for the
      cell.

PMID- 11569917
TI  - The relevance of flow cytometry for biochemical analysis.
AB  - Flow cytometry (FCM) allows the simultaneous measurement of multiple
      fluorescences and light scatter induced by illumination of single cells or
      microscopic particles in suspension, as they flow rapidly through a sensing area.
      In some systems, individual cells or particles may be sorted according to the
      properties exhibited. By using appropriate fluorescent markers, FCM is unique in
      that multiple structural and functional parameters can be quantified
      simultaneously on a single-particle basis, whereas up to thousands of biological
      particles per second may be examined. FCM is increasingly used for basic,
      clinical, biotechnological, and environmental studies of biochemical relevance.
      In this critical review, we summarize the main advantages and limitations of FCM
      for biochemical studies and discuss briefly the most relevant parameters and
      analytical strategies. Graphical examples of the biological information provided
      by multiparametric FCM are presented. Also, this review contains specific
      sections on flow cytoenzymology, FCM analysis of isolated subcellular organelles,
      and cell-free FCM.

PMID- 11569918
TI  - Ketone bodies, potential therapeutic uses.
AB  - Ketosis, meaning elevation of D-beta-hydroxybutyrate (R-3hydroxybutyrate) and
      acetoacetate, has been central to starving man's survival by providing nonglucose
      substrate to his evolutionarily hypertrophied brain, sparing muscle from
      destruction for glucose synthesis. Surprisingly, D-beta-hydroxybutyrate
      (abbreviated "betaOHB") may also provide a more efficient source of energy for
      brain per unit oxygen, supported by the same phenomenon noted in the isolated
      working perfused rat heart and in sperm. It has also been shown to decrease cell
      death in two human neuronal cultures, one a model of Alzheimer's and the other of
      Parkinson's disease. These observations raise the possibility that a number of
      neurologic disorders, genetic and acquired, might benefit by ketosis. Other
      beneficial effects from betaOHB include an increased energy of ATP hydrolysis
      (deltaG') and its linked ionic gradients. This may be significant in drug
      resistant epilepsy and in injury and anoxic states. The ability of betaOHB to
      oxidize co-enzyme Q and reduce NADP+ may also be important in decreasing free
      radical damage. Clinical maneuvers for increasing blood levels of betaOHB to 2-5
      mmol may require synthetic esters or polymers of betaOHB taken orally, probably
      100 to 150 g or more daily. This necessitates advances in food-science technology
      to provide at least enough orally acceptable synthetic material for animal and
      possibly subsequent clinical testing. The other major need is to bring the
      technology for the analysis of multiple metabolic "phenotypes" up to the level of
      sophistication of the instrumentation used, for example, in gene science or in
      structural biology. This technical strategy will be critical to the
      characterization of polygenic disorders by enhancing the knowledge gained from
      gene analysis and from the subsequent steps and modifications of the protein
      products themselves.

PMID- 11569919
TI  - Individual variation in hepatic aldehyde oxidase activity.
AB  - Aldehyde oxidase (AO) is a molybdo-flavo enzyme expressed predominantly in the
      liver, lung, and kidney. AO plays a major role in oxidation of aldehydes, as well
      as oxidation of various N-heterocyclic compounds of pharmacological and
      toxicological importance including antiviral (famciclovir), antimalarial
      (quinine), antitumour (methotrexate), and nicotine. The aim of this study was to
      investigate cytosolic aldehyde oxidase activity in human liver. Cytosolic AO was
      characterised using both the metabolism of N-[(2-dimethylamino)ethyl] acridine-4
      carboxamide (DACA) and benzaldehyde to form DACA-9(10H)-acridone (quantified by
      HPLC with fluorescence detection) and benzoic acid (quantified
      spectrophotometrically). Thirteen livers (10 female, 3 male) were examined. The
      intrinsic clearance (Vmax/Km) of DACA varied 18-fold (0.03-0.50 m/min/mg). Vmax
      ranged from 0.20-3.10 nmol/ min/mg, and Km ranged from 3.5-14.2 microM. In the
      same specimens, the intrinsic clearance for benzaldehyde varied 5-fold (0.40-1.8
      ml/min/mg). Vmax ranged from 3.60-12.6 nmol/min/mg and Km ranged from 3.6-14.6
      microM. Furthermore, there were no differences in AO activity between male and
      female human livers, nor was there any relationship to age of donor (range 29-73
      years), smoking status, or disease status. In conclusion, our results showed that
      there are variations in AO activity in human liver. These variations in aldehyde
      oxidase activity might reflect individual variations or they might be due to AO
      stability during processing and storage.

PMID- 11569920
TI  - Nuclear factor of activated T cells (NFAT1-C) represses the enhancer II and
      pregenomic promoter (EnII/Cp) of hepatitis B virus (HBV) through its responsive
      site GGAGA and nullifies the HBx-driven transcriptional activation.
AB  - The immunosuppressant cyclosporin A (CsA)-sensitive nuclear factor of activated T
      cells 1 (NFAT1) has been known to be a transcriptional regulator of cytokine and
      viral genes during the immune response. By analyses of serial deletion, mutation,
      and heterologous promoter assay, we report here that the CsA-sensitive NFAT1-C
      represses the transcriptional activity of enhancer II and pregenomic promoter
      (EnII/Cp) of HBV through the NFAT1-C responsive site (GGAGA, nt 1603-1618) and
      nullifies the HBx-driven transcriptional activation of the EnII/Cp of HBV in a
      dose-dependent manner. These results suggest that a CsA-sensitive NFAT1-C may
      control the viral activity in HBV-infected cells by inhibiting the EII/Cp and
      nullifying the HBx-driven transcriptional activation.

PMID- 11569921
TI  - Enhancement of oxidative damage to cultured cells and Caenorhabditis elegans by
      mitochondrial electron transport inhibitors.
AB  - The mechanisms that lead to mitochondrial damage under oxidative stress
      conditions were examined in primary and cultured cells as well as in the nematode
      Caenorhabditis elegans (C. elegans) treated simultaneously with electron
      transport inhibitors and oxygen gas. Oxygen loading enhanced the damage of PC 12
      cells by thenoyltrifluoroacetone (TTFA, a complex II inhibitor), but did not by
      rotenone (a complex I inhibitor), antimycin (a complex III inhibitor), and sodium
      azide (a complex IV inhibitor). In primary hepatocytes, the enhancement was
      observed with the addition of sodium azide and rotenone, but not by TTFA or
      antimycin. In the nematode, only rotenone and TTFA enhanced the sensitivity under
      hyperoxia. These results demonstrate that highly specific inhibitors of electron
      transport can induce oxygen hypersensitivity in cell levels such as PC 12 cells
      and primary hepatocytes, and animal level of C. elegans. In addition the cell
      damage is different dependent on cell type and organism.

PMID- 11569922
TI  - Critical role of type IV collagens in the growth of bile duct carcinoma. In vivo
      and in vitro studies.
AB  - Most extrahepatic bile duct carcinomas (EBDC) are characterized by a striking
      stromal response (desmoplasia). Our previous studies showed deposition of type IV
      collagen in the desmoplastic stroma beyond the basement membrane. Although type
      IV collagen is expressed in EBDC, little is known about the pattern of deposition
      in tumor stroma and how this matrix component influences the behavior of tumor
      cells. With the progression of desmoplasia in EBDC, different changes occurred in
      the quantity and localization of type IV collagen from that of type I collagen.
      Type I collagen was diffusely distributed in the stroma and appeared to be
      concentrated in the center of the tumors. In contrast, type IV collagen was
      deposited in the interstitium alongside carcinoma cells at the tumors' periphery.
      Weak or no type IV collagen deposition was detected in the more central portion
      of the tumors containing sclerotic collagens. To investigate the role of stromal
      type IV collagen in tumor cell proliferation, EBDC cell lines were cultured in a
      three-dimensional matrix containing varying compositions of type I collagen and
      type IV collagen. They were also assayed for cell adhesion and migration using in
      vitro models. Type IV collagen more extensively stimulated tumor cell
      proliferation, adhesion and migration in a dose-dependent manner than did type I
      collagen. All of these results suggest that modified tumor stroma with the
      presence of type IV collagen in EBDC provides a better environment for tumor
      growth and invasion.

PMID- 11569924
TI  - p53 in surgically treated and pathologically staged cervical cancer: correlation
      with local tumor progression, but not with lymphatic spread.
AB  - There is only limited information about the prognostic value of p53
      immunostaining in cervical cancer. The purpose of this study was to assess the
      clinical significance of p53 and prognosis in operatively treated cervical
      carcinoma. A hundred and fourteen primary surgically treated cervical carcinomas
      (CX) were obtained from the so called Wertheim Archive in the Department of
      Obstetrics and Gynecology at the University of Leipzig. These included 105
      squamous cell cancer (SCC) and nine adenocarcinomas (AC). No cases received
      neoadjuvant therapy. For immunohistochemical analysis, the cases were tested with
      the monoclonal antibody DO-7 (DAKO Diagnostics, Denmark). Two hundred tumor cell
      nuclei were counted for positive nuclear immunostaining, regardless of staining
      intensity. Cases were stated as positive when a minimum of 10% nuclei showed
      positive staining. Fresh frozen tissue was available from 21 CX for p53-mutation
      analysis (exons 4-9) using PCR-based amplification and SSCP-analysis. Of the
      squamous cell cancers (SCC), 63.8% showed positive nuclear p53-immunostaining;
      adenocarcinomas (AC) were completely negative (P = 0.0000, Chi2-test). Stage-by
      stage analysis revealed no differences in p53-expression. However, combining pT1b
      and pT2-cases, the difference in positive immunostaining reached statistical
      significance (44.4% vs. 71.7%; P = 0.007). There were no differences in p53
      reactivity regarding the presence of pelvic lymph node metastases, tumor grading,
      relapse-free survival and tumor recurrence. In addition, only 5% of CX with
      positive p53-immunostaining showed genomic alterations in mutational analysis.
      p53-immunoreactivity showed significant correlation with local tumor progression
      but not with lymphatic spread, lacking any prognostic impact in surgically
      treated cervical cancer. There is no correlation of p53-immunostaining with the
      occurrence of p53-gene mutations in cervical cancer.

PMID- 11569923
TI  - "Low-risk" and "high-risk" HPV-infection and K-ras gene point mutations in human
      cervical cancer: a study of 31 cases.
AB  - To analyze the coexistence of human papilloma virus (HPV) infection and K-ras
      gene activation in cervical neoplasia, we investigated 31 (seven pre-invasive and
      24 invasive) cervical carcinomas for "low-risk" (types 6 and 11) and "high-risk"
      (types 16 and 18) HPVs and K-ras point mutations using PCR-based technology. "Low
      risk" HPVs were not detected in the group investigated; however, 20 of 31 (64%)
      cases were HPV 16 positive, while HPV 18 was found in only three (9.7%) samples
      (HPV 6/11 v. HPV 16/18, p < 0.0001; HPV 16 v. HPV 18, p < 0.0001; Fisher's exact
      test). There was a K-ras codon 12 point mutation in two of 31 (6.4%) neoplasms,
      with none of the cases showing a K-ras codon 13 point mutation. Two moderately
      differentiated squamous carcinomas showed K-ras exon 2 gene alterations.
      Interestingly, none of the pre-invasive cervical carcinomas displayed K-ras gene
      point mutations. The mean patient age did not differ significantly in the number
      of HPV-positive and -negative cases. A coexistence of "high-risk" human
      papillomavirus DNA with K-ras gene alterations was observed in three of 31 (9.7%)
      neoplasms (one IIA and two IB moderately differentiated cervical carcinomas). Our
      results suggest that "high-risk" HPVs coexist with K-ras gene alterations in a
      subset of moderately differentiated carcinomas of the cervix uteri.

PMID- 11569925
TI  - Immunohistological analysis of thymoma by molecules differentially expressed in
      the thymic cortex and medulla, and its application in the differential diagnosis
      of thymoma from esophageal and lung cancer.
AB  - The purpose of this study was to verify the WHO classification of thymic tumors
      using immunohistological methods, and to discover whether these methods can be
      applied to differentiate thymoma from squamous cell carcinoma (SCC) of the
      esophagus and the lung. Twenty-nine thymoma cases were classified according to
      WHO and were then immunohistologically examined for the positivity of these
      molecules. All thymoma cases investigated in this study were positive for IL-1R,
      and most of them were also positive for bek. In contrast, UH-1 was highly
      positive in B1 and B2 type thymomas, but negative or weakly positive in A, AB and
      B3 type thymomas. Twelve esophageal cancers and 21 lung cancers were also
      examined for the positivity of the same molecules. All esophageal cancers were
      negative for UH-1. Three of 12 cases were weakly positive for IL-1R, and four of
      these 12 cases were also weakly positive for bek. Twelve of 21 lung cancer cases
      were adenocarcinomas, all of them negative for IL-1R, bek and UH-1. Nine of 21
      lung cancer cases were SCCs, all of them negative for UH-1. Eight of nine SCC
      cases were strongly positive for IL-1R, while seven of these were weakly positive
      for bek. We conclude that the WHO classification of thymic tumors is still valid
      as demonstrated by immunohistological analysis and that the positivity of UH-1,
      IL- 1R and bek might be helpful in differentiating thymoma from SCC of the
      esophagus and the lung.

PMID- 11569926
TI  - Salivary duct carcinoma--a highly aggressive salivary gland tumor with HER-2/neu
      oncoprotein overexpression.
AB  - Salivary duct carcinoma (SDC) is a highly malignant salivary gland tumor with
      aggressive clinical behavior, and is characterized by its histological
      resemblance to invasive ductal carcinoma of the breast. Overexpression and/or
      amplification of proto-oncogene Her2/neu has been shown to influence both
      prognosis and treatment of breast cancer. Since salivary duct carcinoma and
      ductal breast carcinoma share many common characteristics, HER2/neu
      overexpression might also be important in SDC. However, data on the expression of
      c-erbB2/HER2/neu in salivary gland tumors are still scarce. Therefore, we have
      evaluated 15 cases of salivary duct carcinomas (SDC) for HER2/neu overexpression
      using immunohistochemistry with the HercepTest. Overexpression, identified as
      strong or moderate membrane immunostaining, was observed in all but one case of
      SDC in most neoplastic cells. Thus, our study suggests that anti-HER2/neu therapy
      with Herceptin is beneficial for patients with aggressive salivary duct
      carcinoma.

PMID- 11569927
TI  - Loss of KAI1/CD82 expression in bone and soft tissue tumors is not associated
      with lung metastasis.
AB  - The KAI1 gene has been identified as a metastasis suppressor gene in human
      prostate cancer. Decrease or loss of KAI1/CD82 expression has been shown to be
      associated with poorer prognosis and metastasis in carcinomas of various organs.
      The purpose of this study was to examine whether KAI1/CD82 is expressed in bone
      and soft tissue tumors, and whether it is associated with metastasis to the
      lungs. Immunohistochemically, KAI1/CD82 expression in benign and malignant soft
      tissue tumors was noted in 83% and 37% of cases, respectively. KAI1/CD82 was-
      also expressed in benign bone tumors and osteosarcomas in 67% and 36% of the
      cases, respectively. Four (40%) of 10 osteosarcoma cases with no lung metastasis
      and one (25%) of four osteosarcoma cases with lung metastasis were positive for
      KAI1/CD82, respectively. Metastasis of osteosarcoma cells to the lungs was not
      correlated with the loss of KAI1/CD82 in osteosarcoma cells.

PMID- 11569928
TI  - An improved method for DNA extraction from paraffin sections.
AB  - The acquisition of comparable quality and quantity of DNA extracts is the
      prerequisite to the success of comparative genetic analyses. Although several DNA
      extracting protocols on paraffin sections have been introduced, the importance of
      deparaffinization, the procedure for obtaining an adequate hematoxylin staining,
      the significance of the ratio of the cell number to the enzyme volume, and a
      practical means for monitoring the digestion process have not been sufficiently
      addressed. These, however, are the most important factors accountable for a
      failure of DNA extraction. To minimize the impact of these factors, we have
      developed several unique strategies, including: (1) incubating sections at 80
      degrees C for 30-60 minutes prior to xylene treatment, (2) checking each section
      to insure the complete removal of paraffin; (3) treating hematoxylin stained
      sections or cells with de-staining solutions; (4) using a micrometer inserted
      into the eyepiece of a microscope to estimate the number of cells collected and
      adjusting the enzyme volume according to the cell number; and (5) monitoring the
      digestion process with a magnifier. With these strategies, we have been able to
      consistently obtain comparable quality and quantity of DNA extracts which yielded
      uniform PCR products regardless of variations in tissue embedding and processing.

PMID- 11569929
TI  - Epithelioid leiomyosarcoma of the uterus with oncocytic change.
AB  - We report on a rare case of epithelioid leiomyosarcoma of the uterus with
      oncocytic change and aggressive clinical behavior. The tumor arose in the left
      lateral wall of the uterus and measured 22 cm in greatest dimension.
      Histologically, it consisted of solid sheets of round and polygonal cells
      displaying a homogeneously eosinophilic cytoplasm and pleomorphic nuclei with
      prominent nucleoli. Six mitotic figures were found per 10 high-power fields in
      the most mitotically active areas, and focal tumor cell necrosis was present
      elsewhere. Under electron microscopy, numerous normal-appearing mitochondria and
      occasional bundles of microfilaments with focal densities were noted in the tumor
      cell cytoplasm, and poorly-formed external basal lamina and occasional pinocytic
      vesicles were found on the cell membrane of some tumor cells.

PMID- 11569931
TI  - 13th Annual Symposium on Transcatheter Cardiovascular Therapeutics. September 11
      16, 2001. Washington, DC, USA. Abstracts.

PMID- 11569930
TI  - Primary cerebral anaplastic large cell lymphoma containing abundant reactive
      histiocytes and eosinophils. A case report and literature review.
AB  - Primary cerebral anaplastic large cell lymphoma (ALCL) is very rare. We report on
      our experience with such a case and review the literature. A 46-year-old
      Taiwanese woman presented with headache, weakness of her right extremity, and
      limited eye movement. A solid mass (5 cm x 4 cm) at the left occipital lobe was
      almost completely removed. The neoplastic cells, some of which had reniform or
      embryo-like nuclei, were large and were admixed with abundant eosinophils,
      histiocytes, and some small lymphocytes. These neoplastic cells expressed CD30,
      CD43, granzyme B and T-cell intracellular antigen-1, but not ALK1, CD3, CD20,
      CD45, CD79a, cytokeratin, and EMA. They were positive for Epstein-Barr virus
      encoded mRNA by in situ hybridization. Polymerase chain reaction study of
      formalin-fixed tissue showed a clonal gene arrangement of the T-cell receptor
      gamma chain. ALCL of T-cell lineage with cytotoxic phenotype was diagnosed. The
      patient received cranial irradiation and has remained with no evidence of disease
      for 25 months of follow-up.

PMID- 11569932
TI  - Prevention of viral drug resistance by novel combination therapy.
AB  - A new form of antiviral clinical therapy is proposed in which three different
      drugs are administered against three different targets on the same virus-coded
      protein. If the physiological functions of the three different target sites are
      not independent of each other, then a mutation conferring drug resistance at one
      site may alter the physiological functions at the other sites and further drug
      resistance may not arise. The adenovirus proteinase, with its two cofactors that
      act synergistically on enzyme activity, may be a good model system within which
      to test the efficacy of this form of combination therapy.

PMID- 11569933
TI  - Entecavir (Bristol-Myers Squibb).
AB  - Bristol-Myers Squibb (BMS) is developing entecavir, a viral replication
      inhibitor, for the potential treatment of hepatitis B virus (HBV) infection
      [220240]. The compound is a cyclopentyl guanosine analog and is in phase II
      trials in the US [383065]. Entecavir was originally developed as SQ-34676 for the
      treatment of herpes simplex virus infections [221992], but displayed only
      moderate activity which eventually led to discontinuation of development for this
      indication. However, Bristol-Myers Squibb later discovered that entecavir was
      extremely potent against HBV (ED50 = 3.0 nM, compared with 200 nM for lamivudine)
      with relatively low toxicity (CC50 = 30,000 nM) [221986] and acted through
      inhibition of DNA polymerase [220240]. The triphosphate form is a potent HBV
      polymerase inhibitor in both woodchuck and duck models [306056]. By September
      2000, a large-scale clinical trial was underway in China for HBV infection
      [400209] and by October 2000 phase I trials were ongoing in Japan [384751]. In
      March 2001 SG Cowen predicted sales of US$25 million in 2002, US$50 million in
      2003 and US$75 million in 2004 [403751].

PMID- 11569934
TI  - Genvir (Flamel Technologies).
AB  - Flamel Technologies is developing Genvir (formerly known as Viropump), a twice
      daily controlled-release formulation of aciclovir, for potential use in the
      treatment of herpes simplex virus and varicella zoster virus infections. Genvir
      utilizes Flamel's proprietary Micropump technology, a microparticle-based drug
      delivery system designed to extend the time of absorption of drugs in the small
      intestine. The drug shows a comparable therapeutic efficacy to valaciclovir and
      famciclovir (both GlaxoSmithKline) [313393]. Phase III trials have been completed
      [302829]. In August 2000, Flamel filed for regulatory approval for the treatment
      of herpes in France, as a prelude to a pan-European approval [378641] and is
      preparing an IND application to begin clinical trials for genital herpes in the
      US [245970].

PMID- 11569935
TI  - Shifting attention from one cell type to another in dermatological research, but
      where are the new drugs?

PMID- 11569936
TI  - Retinoids for the treatment of psoriasis: outlook for the future.
AB  - Despite the demonstrated clinical success of retinoid therapy in psoriasis, its
      mechanism of action has not been fully elucidated, and investigators are
      confronted with two paradoxes. Firstly, the binding of retinoids to nuclear
      retinoic acid receptors (RARs) does not match their therapeutic efficacy.
      Secondly, formation of retinoic acid is probably increased in the psoriatic
      lesions. Answering these questions should result in: (i) the better use of
      acitretin, an oral synthetic retinoid, and tazarotene, the first compound for
      topical use; (ii) the development of new retinoids with specific pharmacological
      profile such as subtype-selective retinoids including molecules with an
      'antiretinoid' activity and dissociating antiproliferative retinoids; and (iii)
      the better characterization of non-genomic effects of retinoids.

PMID- 11569937
TI  - Alefacept (Biogen).
AB  - Alefacept (B-9273) is an LFA-3-Ig fusion protein CD2 antagonist under development
      by Biogen for the potential treatment of autoimmune diseases, including psoriasis
      and transplant rejection [270267]. It is in phase III trials for psoriasis
      [349467]. In October 2000, the company reported that Amevive was on track for
      regulatory filing in the second half of 2001 [385250], with a possible launch in
      the second half of 2002 [395628]. The company began a pivotal phase III trial in
      the US in December 1999, involving patients with chronic plaque psoriasis
      [349467]. A second phase III trial has also been initiated [362199], [374040].
      Results from both trials are expected in mid-2001 [396544]. In April 2001,
      SalomonSmithBarney confirmed that a regulatory filing was expected in Europe and
      the US in the second half of 2001 and stated that alefacept would be critical to
      the future earnings growth of the company [407796]. In June 1999, Merrill Lynch
      estimated product launch in 2001 [327145], [344773]. Sales in 2001 and 2002 were
      anticipated to be US $20 million and US $100 million, respectively [327145].

PMID- 11569938
TI  - IDEC-114 (IDEC).
AB  - IDEC is developing a PRIMATIZED-anti-B7 antibody (IDEC-114) for the treatment of
      autoimmune and inflammatory diseases, such as psoriasis and rheumatoid arthritis.
      It is currently undergoing phase II trials in patients with psoriasis [395813]. A
      randomized, blind, placebo-controlled, multiple-dose phase II study was initiated
      in January 2001 to evaluate the potential clinical activity and safety of IDEC
      114 in patients with moderate-to-severe psoriasis [395813]. The antibody targets
      the B7 antigen on the surface of antigen-presenting cells that normally interact
      with T-cells to initiate an immune response. Antibodies directed at B7 may be
      useful in preventing unwanted immune responses in autoimmune diseases such as
      systemic lupus erythematosus, idiopathic thrombocytopenic purpura as well as
      transplant rejection [178382], [178929]. PRIMATIZED antibodies, genetically
      engineered from cynomolgus macaque monkey and human components, are structurally
      indistinguishable from human antibodies. They may, therefore, be less likely to
      cause adverse reactions in humans, making them potentially suited for long-term,
      chronic treatment [244805]. IDEC has signed an antibody humanization patent
      licensing agreement with Protein Design Labs [240591]. IDEC is also collaborating
      with Mitsubishi-Tokyo (formerly Mitsubishi Kasei) on the development of this
      antibody [178382].

PMID- 11569939
TI  - Cell therapy approaches for the treatment of diabetes.
AB  - Pancreatic beta-cell replacement represents an attractive approach for treatment
      of type 1 and insulin-requiring type 2 diabetic patients. This prospect is
      currently restricted by the limited availability of donor cells. Recent
      developments, including beta-cell expansion by reversible immortalization, and
      generation of beta-cells by differentiation from embryonic and adult tissue
      progenitor cells, may provide abundant sources of cultured human beta-cells. Such
      cells could be genetically modified, as well as encapsulated in semi-permeable
      membranes, to increase their resistance to recurring autoimmunity (in type 1
      diabetics) and to beta-cell degenerative agents (in type 2 diabetics).

PMID- 11569940
TI  - Treatment of gynecomastia.
AB  - Gynecomastia is a common problem during puberty as well as later adulthood, and
      is caused by hormonal imbalance at the breast tissue level. Various medications
      and medical conditions can cause gynecomastia and when the drug is discontinued
      or medical condition cured, it will frequently resolve. Medical therapy can be
      tried for patients with persistent gynecomastia associated-tenderness or social
      embarrassment prior to contemplating surgical removal of the breast tissue.

PMID- 11569941
TI  - CLX-0901 (Calyx Therapeutics).
AB  - Calyx Therapeutics is developing the insulin sensitizer, CLX-0901, as an
      antidiabetic agent. CLX-0901 is the synthetic analog of CLX-0900 which was
      originally isolated from a plant source. Phase I and toxicological studies
      indicate that the compound is safe and well tolerated [363764]. As of March 2001,
      phase II studies had commenced [402737]. Other antidiabetics being investigated
      by Calyx include CLX-0301, CLX-0921, CLX-0940, CLX-0100 and CLX-0101 [376032].

PMID- 11569942
TI  - Therapeutic strategies to retard neuronal cell death in neurodegenerative
      diseases.

PMID- 11569943
TI  - Pathogenesis of Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder
      characterized by degeneration of the nigrostriatal dopaminergic pathway and the
      appearance of cytoplasmic proteinaceous aggregates known as Lewy bodies. Studies
      of familial PD have uncovered rare causative mutations in genes, including alpha
      synuclein. Mutations or oxidative modification of alpha-synuclein causes it to
      aggregate; alpha-synuclein is a major component of the Lewy body in both familial
      and sporadic PD. Biochemical analysis has implicated mitochondrial dysfunction in
      PD. Epidemiological studies indicate a role of exposure to pesticides, some of
      which are mitochondrial toxins. Mitochondrial dysfunction, resulting from genetic
      defects, environmental toxins, or a combination of the two, may cause alpha
      synuclein aggregation and produce selective neurodegeneration through mechanisms
      involving oxidative stress and excitotoxicity. Efforts to better define PD
      pathogenesis should reveal novel therapeutic targets.

PMID- 11569944
TI  - AN-1792 (Elan).
AB  - Elan is developing AN-1792 as a potential immunotherapy for Alzheimer's disease
      (AD). It is currently in phase I trials [350904]. Phase II/III trials, running in
      parallel in the US and UK, are expected to start by the end of 2001 [375061],
      [383226], [401966]. American Home Products (AHP) are collaborating with Elan on
      research and development of an immunotherapy directed towards the beta-amyloid
      peptide, including AN-1792 and other potential products [361702]. In September
      2000, an agreement was established between Elan, AHP and Cambridge Antibody
      Technology (CAT), whereby CAT are investigating anti-beta-amyloid human
      antibodies [394844]. In July 2000, Merrill Lynch predicted a possible late-2001
      entry into pivotal trials with a potential NDA filing in 2004 [375966]. The
      clinical program is expected to take approximately four years [339630]. In April
      2001, ABN Amro Hoare Govett stated that, if data from the large phase II trial
      expected to start late in 2001 satisfied FDA requirements, then Elan might be
      able to file an NDA in 2003, with a potential launch in 2005 [407412].

PMID- 11569945
TI  - KW-6002 (Kyowa Hakko Kogyo).
AB  - Kyowa Hakko is developing KW-6002, an adenosine A2A receptor antagonist, for the
      potential treatment of Parkinson's disease (PD) [183211]. The company
      subsequently began evaluating the compound for depression, and in June 2000
      initiated a phase II trial for this indication. Good results have been obtained
      in a preclinical depression model and Kyowa Hakko hopes that KW-6002 will be
      representative of a new class of antidepressants [376107]. KW-6002 is undergoing
      phase II trials for PD in Japan [343257] and in Europe, including the UK
      1271929], [321641], [402754]. As expected, KW-6002 entered phase II trials for PD
      in the US in October 1999 [321640], [342643], [360980], [402754]. The drug is of
      particular interest due to the absence of the involuntary movement adverse
      effects characteristic of L-DOPA therapy [271929]. Roche was to codevelop KW-6002
      with Kyowa in the US and Europe, but withdrew from the development of this drug
      in April 1999 [321640]. Kyowa will continue with the drug's development in the US
      [321640]. NDAs are estimated to be filed around the end of 2001 and the drug is
      expected to be launched in Western Europe during 2002. An NDA is expected to be
      filed in Japan approximately three to four years later than in Western Europe
      [271929].

PMID- 11569946
TI  - Developing novel and highly effective new therapeutic strategies for treatment of
      colorectal cancer: where do we go from here?

PMID- 11569947
TI  - Sulindac and its derivatives: a novel class of anticancer agents.
AB  - It has been repeatedly observed that non-steroidal anti-inflammatory drugs, in
      particular sulindac and derivatives, may effectively prevent colorectal cancer.
      It has become apparent that exisulind (sulindac sulfone) induces apoptosis in
      tumor cells. Cell biological studies provided circumstantial evidence that the
      mechanism by which these agents exert their antitumor effect should be attributed
      to inhibition of cyclic-GMP phosphodiesterase (cGMP-PDE). The secondary increase
      of cGMP activates protein kinase G (PKG) and induces transcription of caspase
      genes, resulting in apoptosis. cGMP-PDEs comprise 11 gene families. Each family
      of PDEs is characterized by their ability to bind and degrade cAMP and cGMP but
      differs in physical and kinetic properties. Any single type of cell expresses a
      limited number of PDE-isoforms in order to regulate cGMP or cAMP levels. The
      majority of PDE inhibitors that have been investigated until now, except
      exisulind and a number of its analogs, do not induce apoptosis in tumor cells.
      Sulindac has a preventive effect on tumorigenesis in patients with polyposis of
      the colon. The anticancer effect of the novel sulindac derivatives has been
      demonstrated in over 50 different tumor cell lines, as well as in animal models
      of a variety of human cancers, such as mammary, prostate, lung and pancreatic
      carcinomas. Selective apoptotic antineoplastic drugs (SAANDs), as developed by
      Cell Pathways Inc, represent a novel class of anticancer agents that target a
      novel form of cGMP-PDE. It is believed that this enzyme is selectively increased
      in precancerous and cancerous cells. By specifically inhibiting the action of
      this particular cGMP-PDE, SAANDs enable various tumor cells to process an
      apoptotic signal and to commit suicide without affecting normal cells. As a
      result, side effects normally associated with traditional chemotherapeutic agents
      are not observed. One of the new compounds, CP-461, appeared < or = 100-fold more
      potent than exisulind in vitro. Studies of human cancer cell lines in vitro and
      dose-ranging phase I/II studies, both oral and iv, are discussed. Combinations of
      CP-461 with other chemotherapeutic agents are well tolerated.

PMID- 11569948
TI  - Apoptosis modulators as cancer therapeutics.
AB  - In the past ten years a wealth of fundamental knowledge delineating the molecular
      mechanism(s) of apoptosis has emerged, and can now be exploited to identify novel
      apoptotic modulators for the treatment of cancer. Two distinct yet complimentary
      classes of non-genotoxic agonists that can selectively kill tumor cells are
      discussed; agents that target 'classical' and 'atypical' apoptotic signaling
      pathways. The goal of agents targeting classical apoptosis and survival pathways
      is to directly modulate key apoptotic regulators such as Bcl-2, Akt/PKB, and p53.
      The aim of agents targeting atypical apoptotic pathways is to target signaling
      cascades whose inhibition remains non-lethal in normal cells, yet is suicidal in
      tumor cells. Such compounds presently under development include inhibitors of
      heat shock protein 90, histone deacetylases and HMG-CoA reductase. Both classes
      of apoptotic modulators have merit and identification of additional agonists of
      this nature will provide the many diverse cytotoxic agents that are required to
      combat the many diseases we call cancer.

PMID- 11569949
TI  - Thymitaq (Zarix).
AB  - Zarix is developing Thymitaq (nolatrexed dihydrochloride) for the potential
      treatment of cancer. It is conducting a phase III trial in the US, Canada, South
      Africa and certain European countries [382746], [397955], [4061471, after review
      and comment by the FDA. One clinical trial may be sufficient for registration
      [405928]. In April 2000, Thymitaq was designated a Fast Track product for the
      treatment of unresectable hepatocellular carcinouna (HCC) by the FDA [364887],
      based on the survival analysis (intent-to-treat) of the Agouron phase II data and
      medical necessity [405928]. The company was expected to file an NDA in 2002
      [367559]. However, as of April 2001, the company was expecting to file an NDA in
      the third quarter of 2003 [405928]. In January 1999, Zarix licensed worldwide
      rights to Thymitaq from Agouron [311213]. Agouron discontinued development of
      Thymitaq, based on an interim analysis of phase II/III trials which showed that
      although the compound was effective as a single agent in head and neck and liver
      tumors, it was not sufficiently better than existing therapeutics to justify
      further development [211844], [270994]. However, in its efforts to complete the
      monitoring of these studies, Zarix discovered that a great majority of patients
      obtained stabilization of disease with Thymitaq treatment [405928]. Zarix will
      focus development efforts on the treatment of HCC. Zarix is developing Thymitaq
      in an iv formulation for the treatment of HCC and, in May 2000, planned to
      initiate phase III trials in the fourth quarter of 2000 [364887]. Patient
      enrollment in a pivotal, phase III trial in patients with unresectable HCC
      comparing Thymitaq to doxorubicin was initiated in September 2000. Unresectable
      HCC is the first indication being pursued for FDA approval and the trial design
      was deemed acceptable in August 2000. The study is a multicenter, multinational
      trial that will utilize approximately 50 sites. It is anticipated that patient
      accrual will be completed within 24 months [378514], 1382746], [384018]. The
      company plans to file for regulatory approval of the product in North America,
      Europe and Japan, and will pursue development of the drug in a variety of
      oncology indications [311213]. The multicenter study is to be conducted as a
      global program with sites in the US, Canada, Europe and South Africa. In January
      2001, the Canadian Therapeutic Products Directorate indicated that the design of
      the phase IX trial was acceptable. Zarix expected patient enrollment in Canadian
      clinical sites to begin in Spring 2001 [397955], [405928]. By April 2001, patient
      enrollment was underway in the US, Italy, Canada, Romania, South Africa and the
      UK. At this time, Zarix also expected to initiate trials in the Czech Republic
      and Germany in the near future and Poland in the summer of 2001 [406147]. By May
      1997, three clinical trials had been conducted in a total of 149 patients with
      HCC [405928]. In two US phase II trials, patients with unresectable HCC treated
      with Thymitaq had a median survival (intent-to-treat) of over 23 weeks with
      published survivals (intent-to-treat) of less than 15 weeks. Thymitaq has no end
      organ toxicity. Side effects are typical of other antimetabolites but are of
      shorter duration [364887], [405928].

PMID- 11569950
TI  - Reports from the Eighth Annual Conference on Retroviruses and Opportunistic
      Infections. Chicago, February 4-8, 2001.
AB  - The Conference on Retroviruses and Opportunistic Infections is a research meeting
      created to provide a forum for basic and clinical science investigators to
      present, discuss, and critique developments in the field of human retrovirology
      and related opportunistic complications. The subjects highlighted are: virology,
      immunology, vaccines, pathogenesis, disease mechanisms in humans and animal
      models, primary/acute infection, host-virus interactions, antiretroviral therapy
      (preclinical, clinical, and complications), clinical pharmacology, opportunistic
      infections, epidemiology and infection control, microbicides, pediatric/maternal
      fetal/women's health, and diagnostics. Following are digests of major reports
      from the conference, as compiled by the National Prevention Information Network
      (NPIN) of the Centers for Disease Control and Prevention (CDC).

PMID- 11569951
TI  - Getting creative. Creativity can be a key to better physical and mental health.

PMID- 11569952
TI  - The AIDS Theatre Project. The play's the thing.

PMID- 11569953
TI  - Building bridges, making music.

PMID- 11569954
TI  - New emphasis in HIV prevention: interventions targeting HIV-positive men.

PMID- 11569955
TI  - Building alliances for world health funding.
AB  - This key moment in history offer the chance for a breakthrough in world health
      for AIDS and many other conditions, as political consensus demands that over 20
      million people with HIV not be left to die without treament. We believe that
      instead of seeking earmarked HIV funding, the AIDS community should work through
      broad health alliances focusing on poor countries, to find several billion
      dollars a year of new funding for projects in HIV, tuberculosis, malaria, other
      infections, vaccines, microbicides, behavioral prevention, research, training,
      nutrition, clean water, and other cost-effective programs.

PMID- 11569957
TI  - AIDSWatch May 5-8: visit your representatives in Washington.

PMID- 11569956
TI  - FDA gives salvage therapy testing a push forward.
AB  - Pharmaceutical companies like to test their drugs in  patients who are less
      seriously ill, so that the drugs will look good. A recent FDA meeting focused
      attention on the need for more trials in advanced patients, the importance of
      long-term safety follow-up for all patients, and how the necessary trials and
      monitoring could be conducted.

PMID- 11569958
TI  - AmFAR HIV/AIDS treatment directory available.

PMID- 11569959
TI  - Tenofovir: Gilead applies for approval; expanded access liberalized.
AB  - Patients who cannot construct a viable antiretroviral regimen with approved drugs
      will now have easier access to tenofovir, a drug that is currently experimental
      but may be approved in about six months. Tenofovir is significant because it
      appears to maintain its antiretroviral activity, with resistant HIV developing
      relatively slowly.

PMID- 11569960
TI  - June 3 demonstration in Washington to mark 20th year of AIDS.

PMID- 11569961
TI  - Updated guidelines for prevention of mother-to-infant transmission.

PMID- 11569962
TI  - Syringe prescription study unexpected bonus: helping long-time users quit drugs.
AB  - A study to see if syringe prescription by physicians could reduce needle sharing
      also found an additional bonus -- helping some clients get off drugs, by getting
      them into medical care and  making possible conversations which otherwise would
      not happen.

PMID- 11569963
TI  - South Africa court case--documents on the Web.

PMID- 11569964
TI  - Questions about HIV causing AIDS? Viral load and T-cell (CD4) counts: why they
      really matter.

PMID- 11569966
TI  - Oral health is important, but often overlooked.
AB  - Providers sometimes neglect to examine HIV patients thoroughly for oral
      infections, mouth ulcers, and other severe dental problems that are associated
      with HIV infections, according to a new study. Primary care providers and HIV
      specialists may assume that patients are receiving regular dental treatment, when
      this often is not the case.

PMID- 11569965
TI  - Advocacy groups dismayed by lack of funding in president's budget.
AB  - HIV/AIDS advocates have expressed dismay, if not surprise, over the proposed
      funding for domestic HIV programs outlined in the budget submitted in the spring
      by President George W. Bush. Despite the reality of rising drug costs and
      increasing numbers of newly infected Americans, the Ryan White CARE Program was
      flat-funded in the proposal. Other programs fared no better, except for research
      and international HIV funding.

PMID- 11569967
TI  - Many patients suffer from 'battle fatigue': survey.
AB  - A new survey underscores the problem of HIV patients' 'battle fatigue,' caused by
      years of taking antiretroviral drugs and coping with their side effects. AIDS
      Alert talks with survey consultant Charles F. Farthing, MD, chief of medicine at
      the AIDS Healthcare Foundation Healthcare Center in Los Angeles and assistant
      clinical professor of medicine at the University of California at Los Angeles, to
      discuss the problem of AIDS battle fatigue and summarize the survey's findings.

PMID- 11569968
TI  - HIV adherence survey findings at a glance.
AB  - The recently released 'Survey on Treatment Adherence by HIV+ People' shows that
      62% of those surveyed who are taking antiretroviral drugs find it difficult to
      adhere to their drug regimen. The survey involved 371 HIV-positive respondents
      out of a database of 2,500 households that have an HIV-positive member. The
      average time survey respondents had been on antiretroviral drugs was six years
      and seven months, with 9% on therapy for less than two years and 28% on therapy
      for 10 years or longer.

PMID- 11569969
TI  - 18-year survivor discusses HIV battle fatigue.
AB  - David Morris, 47, is the very picture of successful HIV antiretroviral therapy.
      He was diagnosed with HIV on Dec. 31, 1983, first began to take AZT in 1985, and
      now is on an antiretroviral regimen that has kept his viral load to undetectable
      levels. Moreover, Morris has thus far avoided some of the more serious side
      effects associated with treatment, including lipodystrophy, bone problems, and
      increased lipid levels. However, Morris, who is an administrator of the wellness
      program at Beth Israel Deaconess Medical Center in Boston, sometimes feels as
      though he is suffering from battle fatigue.

PMID- 11569970
TI  - Teen intervention program reduces at-risk behavior.

PMID- 11569971
TI  - HIV hypochondria.

PMID- 11569972
TI  - HIV prevention for the third decade of AIDS. The need for a renewed commitment.

PMID- 11569973
TI  - Collected wisdom on your first steps out of prison.

PMID- 11569974
TI  - Under lock and key: youth under the influence of HIV.

PMID- 11569975
TI  - Overcoming the fear in prison: the HAAP experience.

PMID- 11569976
TI  - Supreme Court upholds federal prohibition against medical marijuana.

PMID- 11569977
TI  - Employment discrimination. Ski patroller refused HIV test, must be reinstated.

PMID- 11569978
TI  - SMLX technologies fined for selling unapproved AIDS test.

PMID- 11569979
TI  - U.S. loses U.N. seat, pledges $200 million to global AIDS fund.

PMID- 11569981
TI  - Women with HIV/AIDS receive less care, insurance coverage.

PMID- 11569980
TI  - HIV medical advances explored at retrovirus conference.

PMID- 11569982
TI  - Stem cell therapy may be effective for treating HIV.

PMID- 11569983
TI  - Indiana governor vetoes mandatory HIV testing for inmates.

PMID- 11569984
TI  - Miss. prisons end HIV segregation in education programs.

PMID- 11569985
TI  - Southern California opens its first HIV/AIDS homeless shelter.

PMID- 11569986
TI  - Large Italian study looks at when to start HAART.

PMID- 11569987
TI  - Can ginseng help suppress HIV?

PMID- 11569988
TI  - Spanish study looks at the effect of nevirapine on the liver.

PMID- 11569989
TI  - Lipodystrophy--nukes vs. protease inhibitors.

PMID- 11569990
TI  - Indinavir and bones: does thickness = strength?

PMID- 11569991
TI  - Fosamax for HIV-related bone problems?

PMID- 11569992
TI  - Glycaemic indices of different varieties of rice grown in Sri Lanka.
AB  - OBJECTIVE: Varieties of red raw rice are widely believed to have a better
      nutritional quality. The physiological effects of consuming different varieties
      of rice may not be so. The glycaemic index has been developed as an indicator of
      the physiological effect of foods. It is the glycaemic response of a 50 g
      carbohydrate portion of food expressed as a percentage of that of a standard. The
      objective of this study was to determine the glycaemic indices of different
      varieties of rice grown in Sri Lanka. DESIGN: Digestible carbohydrate content of
      11 varieties of rice flour and bread were determined. Fasting blood samples
      followed by half-hourly samples for two hours were drawn after giving portions of
      either cooked rice or bread containing 50 g carbohydrate each. SETTING: Fibre
      mill in Gampaha district. SUBJECTS: Twenty-two fibre mill workers aged between 25
      and 50 years. MEASUREMENTS: The area under the blood glucose curve (AUC) for
      varieties of rice for a subject was calculated. Average AUC of 3 values for bread
      were calculated. Glycaemic index of each variety of rice was determined from the
      above variables. RESULTS: Glycaemic indices of varieties of rice differ. The
      glycaemic indices of varieties of red raw rice varied between 56 and 73 and the
      variety Bg 350 had the lowest glycaemic index. There was no significant
      difference between mean glycaemic index of varieties of white raw and some
      varieties of red raw rice (p = 0.2). Parboiled varieties of red raw rice had a
      significantly lower glycaemic index than white raw rice (p = 0.04) and some of
      the red raw rice (p = 0.005). CONCLUSIONS: The glycaemic index cannot be
      predicted from the colour of the rice grain. Red parboiled varieties of rice and
      Bg 350 can be recommended for patients with diabetes.

PMID- 11569993
TI  - Pattern of accidents and injuries involving three-wheelers.
AB  - OBJECTIVE: To study the pattern of injuries and some causative factors of three
      wheeler related accidents. DESIGN: Prospective descriptive study. SETTING:
      Accident unit, Colombo South Teaching Hospital, Kalubowila. METHODS: One hundred
      patients admitted to Colombo South Teaching Hospital with three-wheeler related
      accidents were interviewed, examined within 24 hours of admission and followed up
      by using a standard questionnaire. Detailed descriptions of the accident and the
      types of injuries were recorded. RESULTS: 54 accidents took place during daytime
      07.00 h to 19.00 h) and the passengers were the commonest victims (40%). Soft
      tissue injury was the commonest injury observed (75%). The second commonest type
      of injury was long bone fractures (21%). Toppling due to a sudden turn of the
      vehicle accounted for 30% of accidents. Of 28 drivers in the study group, 25
      admitted breaking the handle-lock to increase the vehicle's turning angle.
      Toppling due to a sudden turn was identified as the cause of the accident in all
      those who had interfered with the handle-lock. At the time of the accident, 89%
      of the drivers and 28.1% of pedestrians were under the influence of alcohol.
      Alcohol was related to 67.4% of the night accidents. CONCLUSIONS: Alcohol
      consumption was recognised as a major contributory factor, in particular for
      night accidents. A strong association was observed between mechanical alteration
      of the vehicle's handle-lock and the risk of accident. Introduction of
      legislation to prohibit handle-lock alteration and strict implementation of the
      law regarding driving under the influence of alcohol would help to reduce three
      wheeler related accidents.

PMID- 11569994
TI  - Three young patients with unusual causes of stroke.

PMID- 11569995
TI  - Stroke subtypes in Sri Lanka--a hospital based study.
AB  - AIM: Data on stroke subtypes in Sri Lanka are limited, mainly due to the
      unavailability of brain imaging facilities in most government hospitals. In two
      leading private hospitals in Colombo, a high proportion of stroke patients have
      computerised tomography (CT) scanning. Hence we studied stroke patients admitted
      to these two hospitals to determine the stroke subtypes. METHODS: A prospective
      study of 103 consecutive first ever stroke patients who were under the care of
      the first author during the period 15 May 1995 to 30 August 1996 were studied.
      Diagnosis of stroke was made according to the WHO definition, and transient
      ischaemic attacks (TIA) were not included. The pathological subtype was confirmed
      by CT scan in 99 patients. RESULTS: The age of the patients ranged from 37 to 94
      years (mean 64.5). 87 patients were over the age of 50 years. The proportion of
      pathological subtypes confirmed by CT scanning was cerebral infarction (CI)
      74.7%, intracerebral haemorrhage (ICH) 19.1% and subarachnoid haemorrhage (SAH)
      62.2%. Of the infarcts 31 (42%) were cortical, 30 (41%) lacunar, 12 (16%)
      cerebellar and brainstem, and 1 (1.3%) was a border zone infarct. CONCLUSION:
      Direct comparisons with stroke subtypes seen in other countries are not valid due
      to differences in methodology. In developed countries in the West cerebral
      infarcts account for about 80% of all first ever strokes and of these 13 to 21%
      are lacunar strokes. Countries in the East (e.g. Japan and Hong Kong) have
      reported a higher proportion of haemorrhages (27% of first ever strokes in Hong
      Kong). In Sri Lanka the proportion of stroke subtypes seem to be intermediate
      between these countries in the West and East. Lacunar strokes are commoner in Sri
      Lanka than in other countries.

PMID- 11569996
TI  - Tragically, massive ovarian oedema mimics malignancy.

PMID- 11569997
TI  - Bilateral phaeochromocytoma during pregnancy.

PMID- 11569998
TI  - Congenital glucose galactose malabsorption.

PMID- 11569999
TI  - Thoracic duct cyst presenting as a left supraclavicular mass.
AB  - Thoracic duct cysts may occur either in the mediastinum or in the neck. The
      majority of such lesions occurring in the neck consist of chylous fistulae and
      are secondary to surgery on the neck. Fewer than five cases have been reported in
      the literature of primary thoracic duct cysts occurring in the neck (1).

PMID- 11570000
TI  - Deep vein thrombosis in Sri Lankans--time to take notice.

PMID- 11570001
TI  - Meckel Gruber syndrome--a single gene cause of recurrent neural tube defects.
AB  - Meckel Gruber syndrome (MGS), an autosomal recessive disorder characterised by
      posterior encephalocoele, multicystic kidneys and post-axial polydactyly should
      be recognised by obstetricians and paediatricians to counsel parents regarding
      the 25% recurrence risk. We report a consanguineous family with MGS affecting
      three infants.

PMID- 11570002
TI  - Health in the Huxleyan tropical island of Pala.
AB  - Huxley's Island: a novel (1962) is a parable on "realistic idealism"--set in an
      imaginary island situated in the Indian ocean between Sri Lanka and Sumatra,
      called Pala. The characters in the story include a doctor, a nurse and several
      patients. The general importance of health as a basic human need is well
      recognised. Vis medicatrix naturae, the natural healing powers of the body, are
      taken account of, along with psychotherapy and drugs. Prevention of illness is
      emphasised and doctors get paid for keeping people well. Since health and illness
      are influenced by a multitude of factors, "we attack on all the fronts at once
      ... from diet to auto-suggestion, from negative ions to medication".

PMID- 11570003
TI  - Primary hypomagnesaemia with secondary hypocalcaemia in an infant.

PMID- 11570004
TI  - Anatomy of the Calot's triangle and its relevance to laparoscopic
      cholecystectomy.

PMID- 11570005
TI  - Maternal prolactin concentrations and lactational behaviour in the early
      postpartum period in women with lactational amenorrhoea.
AB  - OBJECTIVE: To compare early postpartum differences in maternal prolactin
      concentrations and lactational behaviour between women who have short and long
      periods of lactational amenorrhoea. METHODS: Healthy lactating women resuming
      regular menstruation before 24 weeks [short amenorrhoea (SA) group; n = 15], and
      at or after 24 weeks [long amenorrhoea (LA) group; n = 15] postpartum were
      studied from 4 to 12 weeks postpartum. Infant feeding pattern and maternal plasma
      prolactin concentrations were compared between the two groups using repeated
      measures ANOVA. RESULTS: Breastfeeds/24 h were significantly higher and other
      feeds/24 h were significantly lower (p < 0.01) at 12 weeks postpartum in the LA
      group when expressed as a percentage of all feeds. Number of breastfeeds
      (total/24 h and night) significantly decreased and the number of other feeds
      significantly increased (p < 0.05 to 0 < 0.001) with time in both groups.
      Prolactin concentrations (basal, suckling stimulated and increment) were higher
      in the LA group, but consistent significant differences were observed mainly in
      the increment (p < 0.05 to p < 0.001). Prolactin concentrations significantly (p
      < 0.01 to < 0.001) decreased with time postpartum in the SA group, but not in the
      LA group. CONCLUSIONS: Women with longer periods of lactational amenorrhoea
      maintain higher prolactin concentrations than those with shorter periods of
      lactational amenorrhoea during the early postpartum period, even when the
      breastfeeding frequency is reduced. This could be explained by a greater
      sensitivity of the pituitary lactotrophe to the suckling stimulus in women who
      have longer periods of lactational amenorrhoea.

PMID- 11570006
TI  - [Molecular regulation of myocardial apoptosis].
AB  - Since apoptosis was described as a process distinct from necrosis, there have
      been many studies of programmed cell death in diseases, especially immunological
      diseases. Because cardiac myocytes are terminally differentiated cells, they have
      typically been assumed to die exclusively by necrosis. However, during the last
      six to seven years this view has been challenged by several studies demonstrating
      that a significant number of myocytes undergo apoptosis in myocardial infarction,
      heart failure, myocarditis, arrhythmogen right ventricular dysplasia, and immune
      rejection after cardiac transplantation, as well as in other conditions of
      stress. These are potentially very important observations, because apoptosis-
      unlike necrosis--can be blocked or reversed at early stages. The tracking of
      cytoprotective and apoptotic signal transduction pathways has proceeded rapidly
      with important new insights into the roles of mitochondria-dependent pathway, Bcl
      2 protein family, p38 mitogen-activated protein kinase, extracellular signal
      regulated kinase and c-Jun N-terminal kinase in cell fate. New studies have
      demonstrated that specific inhibition of apoptosis and activation of
      cytoprotective mechanisms, based on the better understanding of the intracellular
      signaling pathways, can significantly protect cardiac myocytes. This review will
      assess progress in cardiac myocyte apoptosis research and report on the current
      status of anti-apoptotic therapy in acute and chronic heart diseases.

PMID- 11570007
TI  - [Changes in the symptoms of bronchial asthma and associated allergic disorders
      from childhood to adult age].
AB  - The aim of the study was to determine the prognosis of bronchial asthma. 145
      adults (96 men, 49 women) with bronchial asthma during childhood were examined
      above age of 28 years (mean age was 37.6, SD: 5.9 years). The patients filled out
      questionnaires about the asthmatic and accompanying allergic symptoms in their
      childhood, age at 18 years and at present. They all were physically examined and
      prick tested with 12 inhalant allergens. 43% of the patients became symptom-free
      but 57% still had intermittent or persisting asthmatic symptoms while growing up.
      More patients had intermittent asthmatic day (59%) and night (67%) symptoms than
      persisting ones (41 and 33%). The accompanying allergic diseases in childhood did
      not definitely affect the prognosis of bronchial asthma. These are more frequent
      in the females, regarding before all the atopic skin disorders. At the age of 18,
      the occurrence of allergic rhinitis was more frequent than in childhood. The
      frequency of other allergic disorders did not change significantly. Among
      patients with asthmatic symptoms, moulds and cat hair allergies were more
      frequent than in the symptom-free group. The long-term prognosis of childhood
      bronchial asthma is relatively good, however only less than 50% of the patients
      has become symptom-free. In most of the adult patients the complaints are
      relatively mild. The indoor allergens may contribute to the occurrence of
      asthmatic symptoms.

PMID- 11570008
TI  - [Significance of anti-nucleosome (anti-chromatin) auto-antibodies in systemic
      lupus erythematosus].
AB  - Systemic lupus erythematosus is characterised by the presence of antinuclear
      autoantibodies (ANA). Native DNA, histone proteins and small nuclear
      ribonucleoproteins (snRNP) are the main targets of these ANA-s, but some of them
      may derive against the entire chromatin, which is composed of the listed
      elements, and also against its fundamental unit, that is nucleosome. Authors
      investigated at the first time the frequency and the concentration of anti
      nucleosome antibodies in a group of 107 consecutively selected Hungarian lupus
      patients. They calculated correlation between these parameters and the activity
      as well as organ--mainly kidney--manifestations of the disease. The frequencies
      of positive anti-nucleosome, anti-dsDNA and anti-histone antibodies were 39.2,
      28.0 and 47.6%, respectively. All the three autoantibodies were present more
      frequently in cases with lupus nephritis, and this correlation was significant by
      statistical respect. Also a positive correlation was found between the
      concentration of these autoantibodies and activity of the diseases (SLE-DAI).
      Results suggest that long disease duration (mean 8.5 year) and consequently low
      disease activity (mean DAI: 3.28) may stand at the background of the relatively
      low occurrence of the measured ANA-s. Besides anti-dsDNA, the determination of
      anti-nucleosome and anti-histone antibodies can be useful in the diagnosis and
      monitoring of SLE. Authors discuss the possible role of anti-nucleosome
      autoantibodies in the pathogenesis of lupus nephritis.

PMID- 11570009
TI  - [Malignant hemangiopericytoma with breast metastasis].
AB  - The authors report on a rare case of malignant hemangiopericytoma. A 56-year old
      female patient had developed a painless node on her left gluteal region 20 years
      ago. Years later, the resistance became tender and was subsequently surgically
      removed. On histology, the lesion was identified as malignant hemangiopericytoma.
      After a symptom-free period of 8 years distant pulmonary metastases arose, which
      were removed by surgery again. Shortly afterwards the patient manifested with
      further metastasis involving the lung again, as well as the abdomen, the skin and
      the breast, leading to the patient's death 2 years later. The authors review the
      literature, clinical course, diagnostic possibilities, prognosis and therapeutic
      options of malignant hemangiopericytomas. Special attention is drawn to the
      unexceptionally long clinical course at this particular malignancy, as well as to
      the late occurrence of metastases and their unusual breast localisation.

PMID- 11570010
TI  - [Papillary renal cell carcinoma].
AB  - The authors present a case of a papillary type renal cell carcinoma. The tumor is
      mostly discovered accidentally; a histopathological evaluation is indispensable
      for an exact diagnosis. Because of a better prognosis, differentiation of this
      tumor type from the classic variant of renal cell carcinoma is necessary,
      however, the contralateral appearance of a second tumor is not to be excluded,
      which necessitates a strict patient follow-up. Prevalence of this tumor is higher
      in patients with chronic dialysis.

PMID- 11570011
TI  - [A hardly known eponym of a well-known effect: Mihaly Somogyi (1883-1971)].

PMID- 11570012
TI  - [Early events of accident insurance in Hungary and their impact on modern
      insurance medicine].

PMID- 11570013
TI  - Enrichment of spreadable fats with polyunsaturated fatty acids omega-3 using fish
      oil.
AB  - Polyunsaturated fatty acids of the omega-3 series, especially very long chain-
      eicosapenta- and docosahexaenoic acid (EPA, DHA)--exert a strongly desirable
      influence on health. However, their intake with the western-style diet is usually
      too low which favours development of many diseases (CVD, cancers, allergies,
      etc.). Nowadays elevation of EPA and DHA intake is commonly recommended, but
      almost the only dietary source of them is seafoods, especially fish. A new way to
      increase the intake of long-chain omega-3 without radical changes of eating
      patterns is enrichment of regularly consumed foods with unhydrogenated fish oil.
      The aim of this study was to establish sensory and nutritionally acceptable
      enrichment level of low-calorie spreadable fats (soft margarine and mix of butter
      and vegetable oil) with EPA and DHA by addition of fish oil preparations (ROPUFA-
      30% EPA, DHA and MARITEX--10%), and evaluation of the stability of enriched
      spreads during storage (sensory and chemical). It was shown that tested
      spreadable fats might be enriched up to 1% EPA, DHA (i.e. 3% ROPUFA, 8% MARITEX),
      and that this had no significant influence on sensory acceptability. Both used
      fish oils which exerted similar influence on the quality of fats. An enriched mix
      of butter and vegetable oil and margarine may be stored up to 3 and 6 weeks
      respectively without significant decrease of quality. Peroxide value and acid
      numbers were not much affected by enrichment and storage. Daily portion (25-30
      g/day) of spreadable fats enriched on the level established in the study may
      provide 0.2-0.3 g EPA, DHA, significantly increasing the amount of long-chain
      omega-3 in the diet above those eaten normally.

PMID- 11570014
TI  - Dietary habit of smokers in a Chinese population.
AB  - The objective of this study is to determine whether smokers have unhealthy
      dietary habits with respect to cardiovascular diseases and cancer. An age and sex
      stratified random sample of the Hong Kong Chinese population aged 25 to 74 years
      (500 men, 510 women) was recruited. A dietary assessment using a food frequency
      method over a 7 day period, together with a lifestyle questionnaire was
      administered by a trained interviewer. Approximately half the men were smokers,
      while only 19/510 women smoked. Smoking was related to lower education level.
      Male smokers had a lower mean daily consumption of fruits, lower carbohydrate and
      carbohydrate percentage calorie intake, higher fat and fat percentage calorie
      intake, and higher vitamin D intake compared with non-smokers. However, the
      differences were small compared with reported differences in Caucasian
      populations. No difference in dietary pattern was noted between female smokers
      and non-smokers. Although there is a tendency for male smokers to have an
      unhealthy dietary pattern with respect to cardiovascular disease and cancer, the
      differences between smokers and non-smokers are small, and together with the
      favourable health features of the Chinese diet, this difference is unlikely to
      add to the risk of these diseases in smokers or be a confounding factor in
      examining the aetiology of smoke-related diseases in this population.

PMID- 11570015
TI  - Micronutrient composition and nutritional importance of gathered vegetables in
      Vietnam.
AB  - This article presents the nutrient composition and nutritional contribution of
      naturally occurring vegetables (NOV) in four villages in Vietnam. The frequency
      of consumption and quantities eaten were evaluated within the overall diet of 101
      and 110 women in the Mekong Delta (flood period and rainy season, respectively)
      and of 103 women in the Central Highlands (rainy season). The concentrations of
      Ca, Fe and Zn were analysed in 28 species, and presence of tannins and phytic
      acid in 19 species. Provitamin carotenoids were determined in 11 species. Over
      90% of the women consumed NOV, and they contributed 43, 72 and 75% (Central
      Highlands, Mekong rainy and Mekong flood period, respectively) of the total
      quantities of vegetables eaten. Aquatic species such as lpomoea aquatica and
      Limnocharis flava, and terrestrial vegetables such as Schismattoglottis
      calyptrata, were among the most commonly consumed vegetables. They were eaten in
      mean daily quantities exceeding 50 g and had high concentrations of Ca, Fe and
      beta-carotene. Other major aquatic vegetables included the stems of Eleocharis
      sp., Nelumbo nucifera and Nymphea lotus, all of which were used as salad
      vegetables and had relatively low nutrient density. The problems of assessing the
      current role of NOV due to lack of data on intakes in the context of the overall
      diets, as well as data on their composition, are addressed.

PMID- 11570016
TI  - Antioxidant activity of some foods containing phenolic compounds.
AB  - This study was designed to determine the total phenols (TP) and total antioxidant
      activity (TAA) of some liquid and solid plant foods that are commonly consumed in
      Turkey. Total phenols were analysed according to the Folin-Ciocalteu method and
      antioxidant activities of these compounds in aqueous phase were assessed by
      measuring their direct ABTS.- radical scavenging abilities. Total phenols varied
      from 68 to 4162 mg/l for liquid foods and from 735 to 3994 mg/kg for solid foods.
      TAA of liquid and solid foods ranged between 0.61-6.78 mM and 0.63-8.62 mM,
      respectively. Total antioxidant activities of foods were well correlated with
      total phenols (r2 = 0.95). According to content of total phenols per serving,
      liquid foods were in the order of black tea > instant coffee > coke > red wine >
      violet carrot juice > apricot nectar > Turkish coffee > grape molasses > sage >
      white wine > linden flower, and solid foods were in the order of red grape >
      raisins > tarhana > dried black plum > dried apricot > grape > fresh paprika >
      fresh black plum > Urtica sp. > cherry > fresh apricot > paprika pickle > paprika
      paste.

PMID- 11570017
TI  - Changes in protein nutritional quality in fresh and recombined ultra high
      temperature treated milk during storage.
AB  - The objective of this study was to determine the changes in nutritional quality
      of protein in stored UHT milk. Commercial fresh and recombined ultra high
      temperature (FUHT and RUHT respectively) treated milk samples were used.
      Pasteurized milk (P-milk) samples were used for comparison. Milk samples were
      freeze-dried for the use in diet formulation. Pasteurized milk samples were
      freeze-dried within 24 h of production. FUHT and RUHT milk samples were freeze
      dried after production (zero time), 3 and 6 months of storage at 37 degrees C.
      Three nitrogen balance experiments were done at zero time, after 3 and 6 months
      of storage. The diet used in all experiments were similar in composition except
      for protein source. In each experiment egg white (low protein), casein (control),
      P-milk, and either 0, 3 or 6 months old FUHT and RUHT milk samples were used as
      the source of protein in the diets. In each experiment 30 (six for each diet)
      male Sprague-Dawley rats were used. Apparent digestibility (AD), true
      digestibility (TD), biological value (BV), and net protein utilization (NPU) were
      calculated for protein in casein and all milk samples. The nutritional quality of
      protein in FUHT milk before storage was similar to that of protein in pasteurized
      milk, but it decreased during storage for 3 months and then remained at the same
      quality up to 6 months of storage. BV and NPU of protein in FUHT milk after
      storage for 3 and 6 months were lower than that of protein in pasteurized milk by
      4% (not significant) and 5% respectively. On the other hand, the nutritional
      quality of protein in RUHT milk before storage was lower than that of protein in
      pasteurized milk and remained at the same level after storage for 3 months:
      however, it decreased significantly after storage for 6 months. AD and TD of
      protein in RUHT milk stored for 6 months were lower than that of protein in
      pasteurized milk by 5% and BV and NPU were lower than that of protein in
      pasteurized milk by 9 and 12% respectively. The above reduction in nutritional
      quality of protein in UHT milk may be of significant value in feeding young
      children who might be dependent on this type of milk in their diet.

PMID- 11570018
TI  - Food consumption and buying patterns of students from a Philippine university
      fastfood mall.
AB  - A consumer survey was conducted in a university fastfood mall to determine the
      food consumption and buying patterns of Philippine university students. The
      survey established that a typical fastfood consumer in the test university
      foodmall is female between 16 and 22 years old, with a purchasing capability of <
      or = US$1.79 for a complete meal, and who generally frequents the mall only once
      a day during weekdays. Wholesomeness, affordability and variety of the foods were
      the general basis for satisfaction of the typical student consumer.

PMID- 11570019
TI  - Nutritional improvement of Lobia (Phaseolus vulgaris) by supplementation with
      poultry, mutton and beef meat.
AB  - The study was conducted to determine the nutritional value of Lobia (Phaseolus
      vulgaris) in raw and cooked forms and as effected by supplementation with
      different kinds of meat, i.e. poultry, mutton and beef at 10, 15 and 20% levels.
      Nutritional assessment of all the Lobia-containing diets (without or with
      supplementation) was made by chemical analysis as well as through rat assay.
      Lobia contained 20.43% of protein. Cooking resulted in minor changes in
      nutrients. It had 0.54% lysine which was reduced to 0.29% on cooking. All other
      amino acids also showed losses during cooking. Protein efficiency ratio (PER) of
      diets containing raw Lobia was 1.05 and significantly (P < 0.05) improved to 1.47
      on cooking. True digestibility (TD) and net protein utilization (NPU) also showed
      a significant (P < 0.05) improvement in the case of cooked Lobia. Supplementation
      of Lobia with 20% of mutton or beef meat improved the PER significantly (P <
      0.05) over unsupplemented diet containing cooked Lobia only. TD was improved from
      74.9% in cooked to 84.3% in diets containing 20% mutton. Similarly NPU improved
      as a result of meat supplementation, from 40.7% in cooked to 53.4%. Higher PER,
      TD and NPU values were observed in diets containing Lobia supplemented with 20%
      level of mutton or beef.

PMID- 11570020
TI  - A benefit-based copay for prescription drugs: patient contribution based on total
      benefits, not drug acquisition cost.
AB  - Several managerial mechanisms have been used by managed care organizations to
      affect prescription drug utilization and related expenditures. Some efforts have
      focused on monitoring clinical conditions, drug use, and compliance, whereas
      other efforts have focused on consumer cost sharing and changing product-mix.
      Efforts focusing on improving quality of care by identifying untreated patients
      or by enhancing compliance can lead to appropriately increased drug costs,
      although perhaps with reduced overall medical expenditures. In contrast, the
      mechanisms implemented to constrain drug costs raise concerns regarding missed
      opportunities to enhance clinical outcomes, and the possibility of higher medical
      expenditures. Cost sharing plays a critical role in defining the pharmaceutical
      benefit. To balance the demands for access to pharmaceuticals with pressures to
      constrain costs, levels of cost sharing must be set in a manner that achieves
      appropriate clinical and financial outcomes. Modern multitier systems often base
      patient contributions on drug acquisition cost, and often do not consider medical
      necessity as a coverage criterion. Using an alternative approach, the benefit
      based copay, patient contributions are based on the potential for clinical
      benefit, taking into consideration the patient's clinical condition. For any
      given drug, patients with a high potential benefit would have lower copays than
      patients with a low potential benefit. Implementation of such a system would
      provide a financial incentive for individuals to prioritize their out-of-pocket
      drug expenditures based on the value of their medications, not their price.

PMID- 11570021
TI  - Effect of moderate weight loss on health-related quality of life: an analysis of
      combined data from 4 randomized trials of sibutramine vs placebo.
AB  - OBJECTIVES: To determine whether (1) patients who experience greater weight loss
      also experience correspondingly greater improvements in health-related quality of
      life (HRQOL); (2) the improvement in HRQOL is noticeable for patients achieving
      moderate (5%-10%) weight reduction; and (3) the relationship between weight
      reduction and HRQOL is similar for patients receiving sibutramine hydrochloride
      vs placebo. STUDY DESIGN: We combined data from 4 double-blind, randomized,
      controlled trials of administration of sibutramine (20 mg/d) vs placebo. PATIENTS
      AND METHODS: Patients (n = 555) were mildly to moderately obese and had type 2
      diabetes mellitus, dyslipidemia, or hypertension that was well controlled with an
      angiotensin-converting enzyme inhibitor or calcium channel blocker. The HRQOL was
      operationalized using the Impact of Weight on Quality of Life (IWQOL) and the
      Medical Outcomes Study 36-Question Short-Form (SF-36) instruments. The main
      statistical technique was a patient-level analysis of variance predicting change
      in HRQOL from study, treatment, and weight change. RESULTS: Moderate weight loss
      was associated with a statistically significant improvement in HRQOL for
      approximately half of the subscales evaluated (P < .05). The greatest sensitivity
      to change was shown by the SF-36 general health perception and change in health
      since last year subscales and the IWQOL overall health, mobility, and total
      subscales. Greater weight loss was associated with the most improvement in HRQOL.
      Weight losses of 5.01% to 10.00% were associated with 2-unit changes in the SF-36
      general health perception subscale and 10-unit changes in the IWQOL total
      subscale. Results were similar across study and treatment. CONCLUSIONS: Moderate
      weight loss is associated with noticeably improved HRQOL. Improvements in HRQOL
      are achievable by patients receiving sibutramine.

PMID- 11570022
TI  - A randomized intervention to improve ongoing participation in mammography.
AB  - OBJECTIVE: To test the effectiveness of interventions intended to increase rates
      of regular breast cancer screening, according to recommended guidelines. STUDY
      DESIGN: A randomized controlled trial of 2 outreach interventions (a mail
      reminder and a telephone reminder plus appointment scheduling) compared with a
      routine publicity campaign to encourage continued participation in mammography
      screening. PARTICIPANTS AND METHODS: Participants were 1908 women aged 50 to 75
      years continuously enrolled in a large group-model HMO during the study who
      underwent a bilateral mammogram during the first quarter of 1994 and no
      subsequent mammogram during the next 18 to 21 months. Data were obtained from
      health plan administrative data files supplemented by medical chart review. Women
      were randomly assigned to receive (1) a mail reminder, (2) a telephone reminder,
      or (3) routine publicity on mammography for all women. The outcome measure was a
      mammogram received after the intervention period and within 2 years of the
      initial mammogram date. RESULTS: Bivariate and multivariate statistical analyses
      showed that participation was significantly higher for women contacted by
      telephone than through routine publicity. Mail reminders were no more effective
      than a routine publicity campaign. Primary care physician and gynecologist visits
      increased the likelihood of a subsequent mammogram for women in all intervention
      groups. CONCLUSIONS: Telephone contact by regular health plan staff was more
      successful than publicity in encouraging continued participation in mammography
      screening in women enrolled in a group-model managed health care plan. Because
      mailings did not influence participation in mammography screening, health plans
      should be cautious about investing in member mailings without first evaluating
      their effectiveness in the context of existing outreach efforts.

PMID- 11570023
TI  - Impact of a targeted asthma intervention program on treatment costs in patients
      with asthma.
AB  - OBJECTIVE: To evaluate the impact of a targeted asthma intervention on treatment
      costs, utilization of medical services, number of prescription drugs filled, and
      trends of medication use from a third-party perspective. STUDY DESIGN:
      Longitudinal population-based study. METHODS: Study asthmatic patients were
      classified into intermittent and persistent asthma groups according to the Health
      Plan Employer Data and Information Set (HEDIS) 2000 asthma measurement. The
      intervention instituted appropriate asthma drug therapy according to National
      Heart, Lung, and Blood Institute guidelines. A paired t test and analysis of
      covariance were used to compare treatment costs and the number of prescriptions
      dispensed in the 9 months before and the 9 months after the intervention.
      RESULTS: The study patients (n = 1616) included 566 with intermittent asthma and
      1050 with persistent asthma. After the intervention, treatment costs per patient
      increased significantly by $122 in the intermittent asthma group (P = .001) but
      decreased significantly by $247 in the persistent asthma group (P < .001). Costs
      incurred by patients with persistent asthma decreased by $149 for hospitalization
      (P = .003), $16 for emergency room visits (P < .001), $82 for physician visits (P
      < .001), and increased by $1 for asthma medications (P = .938). The number of
      asthma medication prescriptions per patient increased by 0.72 prescriptions in
      the intermittent asthma group (P < .001), whereas the persistent asthma group had
      a per patient reduction of 0.99 prescriptions (P < .001). CONCLUSION: A targeted
      asthma intervention resulted in decreased hospitalization, emergency room, and
      physician visit costs in patients with persistent asthma.

PMID- 11570024
TI  - Comparison of prevalence, cost, and outcomes of a combination of salmeterol and
      fluticasone therapy to common asthma treatments.
AB  - OBJECTIVES: To compare a combination of salmeterol and fluticasone with common
      asthma pharmacologic regimens used in real-world clinical practice, and to
      evaluate the associated costs and outcomes of care. STUDY DESIGN: Cross-sectional
      examination of medical and pharmacy claims. METHODS: The study population
      included 33,939 adult asthmatics (at least 12 years of age) continuously enrolled
      in 1 of 4 participating health plans for the 6-month study period. Every subject
      was in 1 of 10 different pharmacotherapy treatment groups. Univariate and
      multivariate analyses were used to compare the rates and costs of pharmaceutical
      prescriptions and medical care services between patients on salmeterol plus
      fluticasone and patients with other pharmacologic therapies. RESULTS: About 60.4%
      of the patients were on single controllers; the balance was on short-acting beta
      2-agonists alone (23%) or double controllers (16.8%). The average overall cost of
      asthma care was approximately $228 per patient over the 6 months of the study.
      Pharmaceutical cost was the major cost driver, which was significantly lower for
      single-controller (mean = $134) than for double-controller therapies (mean =
      $325). However, total costs were $50-$200 lower (P < .029) for patients on
      salmeterol plus fluticasone and inhaled steroids plus mast cell stabilizing
      agents than for those on other double controllers. CONCLUSIONS: Single-controller
      regimens and short-acting beta-agonists were less costly than double-controller
      regimens. Within the double-controller groups, salmeterol plus fluticasone
      appeared to be less costly than other double controllers, except inhaled steroids
      plus mast cell stabilizing agents.

PMID- 11570025
TI  - Weight loss and health-related quality of life.

PMID- 11570026
TI  - Current perspectives on the diagnosis and treatment of major depressive disorder.
AB  - Each year in America approximately 6 million people suffer from depression at a
      cost of more than $16 billion. People who are depressed have more medical
      illnesses than those without depression and make greater use of healthcare
      services. In a 15-month period after having been diagnosed with depression,
      sufferers are 4 times more likely to die as those who do not have depression.
      Almost 60% of suicides have their roots in major depression, and 15% of those
      admitted to a psychiatric hospital for depression eventually kill themselves.
      Although depression is highly treatable, only one third of sufferers receive
      suitable treatment. The reason for underdiagnosis is 2-fold. Physicians may fail
      to recognize depression and sufferers may actively deny it. A family history of
      depression is an important cause in those who suffer recurrent episodes. Major
      depressive disorder is the most common type of depression and, unless treated,
      resolves by itself in 6 months to a year less than 40% of the time. Depressive
      symptoms can be found in as many as 30% of those who abuse alcohol, so abstinence
      is crucial to treatment. Contrary to popular belief, depression is not a normal
      part of aging, although it can occur in elderly people who have severe medical
      and psychosocial problems. The goal of pharmacotherapy is the reduction and
      ultimate removal of all signs and symptoms of depression. More than 2 dozen drugs
      with 7 distinct mechanisms of action are available to treat depression, with the
      clinical goal being remission. Whereas psychotherapy is a treatment option, by
      itself it tends to be effective in only a limited group of highly motivated
      individuals who have less severe forms of depression. As a result, treatment
      outcomes are better when pharmacologic antidepressant treatment and psychotherapy
      are combined.

PMID- 11570027
TI  - Recent perspectives on the diagnosis and treatment of generalized anxiety
      disorder.
AB  - Anxiety disorders are common mental disorders, encompassing a group of conditions
      that share extreme or pathological anxiety as the primary disturbance in mood or
      emotional tone. Anxiety disorders include generalized anxiety disorder (GAD),
      panic disorder, agoraphobia, specific phobias, social anxiety disorder, obsessive
      compulsive disorder, and posttraumatic stress disorder. Individual anxiety
      disorders have considerable symptomatic overlap in their expression. The life
      time prevalence of all anxiety disorders in the general population is about 25%.
      There is familial aggregation of anxiety and mood disorders such as major
      depression. Genetic factors and life experiences both contribute to the
      likelihood of developing anxiety disorders. GAD is characterized by excessive
      anxiety and uncontrollable worry, is present for longer than 6 months, and tends
      to occur comorbidly with other conditions, including other anxiety disorders and
      major depression as well as general medical conditions. GAD, given its chronic
      nature, is associated with significant impairment. GAD is responsive to
      pharmacological treatments, such as anxiolytics and antidepressants, as well as
      psychotherapies such as cognitive therapy.

PMID- 11570028
TI  - The clinical, psychosocial, and pharmacoeconomic ramifications of remission.
AB  - At an estimated cost of almost $50 billion a year, the socioeconomic burden of
      major depressive disorder is enormous. Although remission has been identified as
      the key goal of treatment, such treatment must be highly acceptable to patients,
      predictably effective, and carry minimal adverse effects. The cornerstone of
      depression management, remission can improve clinical status, functional ability,
      and quality of life for the patient while lowering utilization costs related to
      the disease and its comorbidities. Initially, the goals of therapy are to: (1)
      reduce and ultimately remove all signs and symptoms of the depressive syndrome;
      (2) restore occupational and psychosocial function to the asymptomatic state; and
      (3) achieve and maintain remission. Most patients can achieve these goals with
      the help of antidepressant medications, problem-focused psychotherapy, or a
      combination of the 2 methods. Following an initial assessment of the patient,
      treatment of depression has 3 phases: acute, continuation, and maintenance.
      Although adherence to treatment is crucial to successful treatment of depression,
      only about 25% to 35% of patients will achieve remission after 6 to 8 weeks of
      treatment; another 15% to 20% may remain depressed for months or years. Patients
      who achieve remission are much less likely to relapse than those who do not. Much
      debate has focused on the relative merits of prescribing selective serotonin
      reuptake inhibitors or venlafaxine. Results of a pooled analysis of 8 such
      comparative studies are presented.

PMID- 11570029
TI  - The pharmacoeconomics of venlafaxine in depression.
AB  - The prevalence of depression and the high costs associated with its management
      have heightened interest in pharmacoeconomic evaluation of drug treatment,
      especially the use of selective serotonin reuptake inhibitors (SSRIs) and the
      serotonin-norepinephrine reuptake inhibitor venlafaxine. A number of studies of
      venlafaxine in both inpatient and outpatient settings have revealed that extended
      release venlafaxine has a lower expected cost than comparable treatment with
      SSRIs and tricyclic antidepressants (TCAs). When the relative cost effectiveness
      of immediate-release venlafaxine, SSRIs, and TCAs was assessed in the treatment
      of major depressive disorder in 10 countries, venlafaxine yielded a lower than
      expected cost compared with SSRIs and TCAs in all but 1 country. In comparing
      healthcare expenditures for depressed patients with and without anxiety, there
      was a pharmacoeconomic benefit to both immediate- or extended-release
      venlafaxine, regardless of the presence or absence of comorbid anxiety. A review
      of computerized administrative claims data from 9 US healthcare plans on resource
      use and the cost of venlafaxine instead of TCAs after switching from an SSRI
      showed that overall costs did not vary markedly between venlafaxine and TCAs.
      This led to the conclusion that although therapy with venlafaxine is more costly
      than TCA therapy, this increase may be offset by lower costs of other medical
      services. Such findings have enormous potential ramifications for practicing
      physicians in terms of venlafaxine's superior remission rate, lower likelihood of
      relapse, loss of fewer patients to adverse events or lack of efficacy, and
      flexibility in dosing that enables titration to achieve an optimal response.

PMID- 11570030
TI  - Nonsteroidal anti-inflammatory drugs, cyclooxygenase inhibitors, and the risk of
      gastrointestinal complications.

PMID- 11570031
TI  - Upper gastrointestinal complications: the causes, consequences, and clinical
      outcomes.
AB  - Studies reveal that cyclooxygenase (COX-2) inhibitors seem to markedly lessen the
      risk of ulcers and upper gastrointestinal complications. Discussion, however,
      continues whether COX-2 inhibitors reduce the risk of clinical events to the same
      degree as nonsteroidal anti-inflammatory drugs.

PMID- 11570032
TI  - Helicobacter pylori and nonsteroidal anti-inflammatory drugs: synergy or null
      effect?
AB  - Both Helicobacter pylori infection and nonselective, nonsteroidal anti
      inflammatory drugs (NSAIDs) contribute to a greater risk of gastric and duodenal
      ulcers, ulcer complications, and gastrointestinal bleeding. Prospective
      investigations are needed to learn what is the net effect of the combination of H
      pylori and NSAIDs.

PMID- 11570033
TI  - Risk stratification in decisions about nonsteroidal anti-inflammatory drug
      cotherapy.
AB  - Successful application of risk stratification in decisions about nonsteroidal
      anti-inflammatory drug (NSAID) therapy could enable patients with a lower
      baseline risk of gastrointestinal (GI) complications to take a nonspecific
      generic NSAID and those with greater risk of GI complications to take the
      cotherapies.

PMID- 11570034
TI  - The importance of addressing the condition of nonsteroidal anti-inflammatory drug
      related gastropathy.

PMID- 11570035
TI  - Sound judgments. Will a powerful new navy sonar harm whales?

PMID- 11570036
TI  - Catching some sun.

PMID- 11570037
TI  - Magnetic revelations.

PMID- 11570038
TI  - Can't read, can't count.

PMID- 11570039
TI  - Tobacco pharming. A quest to turn the killer crop into a treatment for cancer.

PMID- 11570040
TI  - Magic bullets fly again.

PMID- 11570041
TI  - Code Red for the Web.

PMID- 11570042
TI  - Driving the info highway.

PMID- 11570043
TI  - Refugees for life in a hostile universe.

PMID- 11570044
TI  - The challenge of macular degeneration.

PMID- 11570045
TI  - Drowning New Orleans.

PMID- 11570046
TI  - Moisture permeability of the total surface bearing prosthetic socket with a
      silicone liner: is it superior to the patella-tendon bearing prosthetic socket?
AB  - The purpose of this study was to examine the moisture permeability properties of
      materials used for total surface bearing (TSB) socket with a silicone liner, a
      combination of Silicone Suction Socket or Icelandic Roll-On Silicone Socket
      (ICEROSS) and an acrylic plastic sheet (Degaplast), patella-tendon bearing (PTB)
      socket, a combination of Pe-Lite and Degaplast, and wooden socket made of poplar.
      Moisture permeability of the socket materials was measured as the diminution of
      water in a container after 12 hours in a climatic chamber. Eight containers with
      their open, top side were uncovered (no material) or sealed with one of the
      socket materials; the experiment was repeated four times. One-way analysis of
      variance followed by Bonferroni's test was applied to examine the differences in
      moisture permeability. Moisture permeability levels were as follows: no material,
      85.9 +/- 1.3 g; poplar, 4.3 +/- 0.4 g; Silicone Suction Socket, 1.1 +/- 0.2 g;
      ICEROSS, 1.0 +/- 0.2 g; Pe-Lite, 0.8 +/- 0.1 g; 3S + Degaplast, 0.8 +/- 0.1 g;
      ICEROSS + Degaplast, 0.8 +/- 0.2 g; and Pe-Lite + Degaplast, 0.8 +/- 0.1 g. There
      were significant differences between the uncovered container and the others, and
      between poplar and the others (P < 0.05). We concluded that the TSB socket with a
      silicone liner is not superior to the PTB socket with regard to moisture
      permeability, and that it is necessary to develop a new prosthetic socket that
      allows heat release and drainage of sweat.

PMID- 11570047
TI  - Risk of Toxoplasma gondii infection in slaughterhouse workers in Kitakyushu City.
AB  - To clarify the risk of Toxoplasma gondii infection among slaughterhouse workers,
      we investigated Toxoplasma antibody in workers and swine in the meat center of
      Kitakyushu City and discussed the result from the standpoint of working
      conditions. Among 67 slaughterhouse workers, 22 were positive for Toxoplasma
      antibody (positive rate, 32.8%), while among 208 swine, 19 were positive
      (positive rate, 9.1%). When classified by ages of workers, positive rates in
      workers were 0% at the age of 30 or less and around 40% at the age of 31 and
      over. Especially, positive rate became as high as 66.7% in workers aged 61 and
      over. Positive rates for Toxoplasma antibody in workers classified by duration of
      employment were 25% for 5 years or less and 41.5% for 6 years and over. Moreover,
      there was no difference in positive rates of Toxoplasma antibody between swine
      slaughterers (positive rate, 32.4%) and cattle slaughterers (33.9%). Although
      overall positive rate of Toxoplasma antibody in slaughterers was higher, positive
      antibody in younger slaughterers or that of shorter duration of employment was
      considerably low. In addition, since positive rate of Toxoplasma antibody in
      swine brought to the slaughterhouse has decreased remarkably in comparison to the
      previous study, risk of toxoplasmosis in slaughterhouse workers also seemed to
      have decreased.

PMID- 11570048
TI  - Items regarded as important for satisfaction in daily life by elderly residents
      in Kitakyushu, Japan.
AB  - The objective of this study was to determine what items were important for
      satisfaction in the daily life of elderly Japanese people living at home. The
      subjects consisted of 996 persons living in Yahatanishi Ward, Kitakyushu City,
      Japan, two percent of residents aged 60 years or over, who were randomly selected
      from the official register of voters. A questionnaire was sent to the subjects to
      determine their profiles and asking them to select the five items they considered
      most important for satisfaction in daily life from 35 predetermined items. The
      items with a significant difference using a chi 2 test between age groups,
      gender, place of residence, living conditions and level of disability were
      analyzed by logistic regression analysis. The top five items selected were "good
      health" (86%), "social security and pension" (47%), "self-care independence"
      (45%), "marital satisfaction" (34%), and a "good relationship with relatives"
      (33%). Logistic regression analysis showed gender, age group, living conditions,
      and level of disability significantly affected the preference for selection of 12
      items. Men or younger persons regarded "health" and a "good relationship with a
      spouse" as very important, whereas women, older persons, or persons with a
      disability considered "self-care independence" and the "ability to walk" as
      important. The items selected for satisfaction in daily life and the order of
      preference yield important information about rehabilitative and social welfare
      services for elderly persons living at home.

PMID- 11570049
TI  - [Relationship between the prevalence of hepatic milk spots in pig and the egg
      density of Ascaris suum in Kitakyushu Municipal Meat Inspection and Control
      Center].
AB  - The hepatic milk spots of pigs are chronic interstitial hepatitis, and are caused
      by the migration of pig ascarid worm, Ascaris suum, into the liver. A large
      number of livers are condemned in meat inspection centers as defective food once
      they are found to have developed milk spots, and thus the economic loss is great.
      Eggs of Ascaris suum from 120 caecum feces of slaughtered pigs were detected by
      the nylon mesh filtration (Makiya) technique and they were related to the
      condemnation data of the milk spot livers in Kitakyushu Municipal Meat Inspection
      and Control Center from April 2000 to February 2001. The condemnation rate was
      continuously more than 50% at some particular pig farms, the average rate being
      as high as 73% during this period. Liver milk spots and Ascarid infection from
      some 200 mg of caecum feces sampled with the template of the filtration technique
      were compared. As a result, a close agreement was observed between the two kinds
      of positive data, and a significant correlation was expected between the average
      egg density (EPG) of sampled pigs and the prevalence rate of milk spots of the
      same groups. These results proved that this filtration technique can be used as
      an effective inspection method for detecting milk spot liver.

PMID- 11570050
TI  - [The characteristics of the fortuneteller--the trend towards the 'voluntary
      knowledge' type of fortuneteller in contemporary Japanese society].
AB  - Fortunetelling is being practiced throughout contemporary Japanese society. The
      fortunetelling is, so to speak, one of 'social facts'. Though we usually see such
      a scene, we do not understand it from the viewpoint of Sociology. To find a clue
      in the sociological study of fortunetelling, the fortuneteller is one of the
      important elements. That is, the fortuneteller is an expert who controls the art
      and knowledge of fortunetelling. In order to analyze fortunetelling sufficiently,
      we first need to clarify the characteristics of the fortuneteller. The purpose of
      this paper is to show what characteristics the fortuneteller has, in terms of two
      distinctions: the first parameter of distinction is the 'ground' which
      legitimatizes fortunetelling; and the second is the 'opportunity' which channels
      people into fortunetelling. The 'ground' rests on either 'inspiration
      (revelation)' or 'body of art and knowledge (hereafter knowledge)'. And the
      'opportunity' rests on either 'voluntary' or 'compulsion'. In analyzing the
      fortuneteller according to 'inspiration'/'knowledge' and
      'voluntary'/'compulsion', the type of fortuneteller who has the characteristics
      of both 'knowledge' and 'voluntary' is prominent. Why is such a type prominent? I
      answer this question by analyzing the relationship between the characteristics of
      the fortuneteller and the social structures.

PMID- 11570051
TI  - [Results of surgical treatment for primary lung cancer; time trends of survival
      and clinicopathologic features].
AB  - To assess whether the survival of patients who underwent surgical resections for
      non-small cell lung cancer (NSCLC) improved, we examined the time trends for
      survival after operation. A total of 851 consecutive patients with NSCLC who
      underwent surgical resections between 1979 and 2000 were retrospectively reviewed
      by 3 groups according to year of the operation: the early period (from 1979 to
      1986, n = 138), the middle period (from 1987 to 1993, n = 288), and the late
      period (from 1994 to 2000, n = 425). There were 606 men and 245 women with a mean
      age of 65.4 years. The histologic type included 453 adenocarcinoma, 282 squamous
      cell carcinoma, and 63 large cell carcinoma. The pathologic stage included 203
      stage I A, 171 stage I B, 21 stage II A, 117 stage II B, 180 stage III A, 123
      stage III B, and 36 stage IV diseases. The mean age at the middle and late
      periods showed a significant increase compared with the early period. There were
      no significant histologic differences among the three periods. The ratio of
      patients with stage I A disease increased significantly at the middle and late
      periods compared with the early period. The 5-year survival rate of the 851
      patients was 43.7%, and the median survival was 44.8 months. The 5-year survival
      rates at the early, the middle, and the late periods were 33.3%, 44.2%, and
      45.8%, respectively, with significant improvement at the middle and late periods
      compared with the early period. The overall 30-day operative mortality was 2.2%
      (19/851): 8.7% (12/138) at the early period, 1.4% (4/288) at the middle period,
      and 0.7% (3/425) at the late period, showing significant decrease during the
      middle and late periods compared with the early period. The postoperative
      prognosis of patients with resected NSCLC during the later periods had a better
      survival, which was caused by an increase in the ratio of patients with stage I A
      disease, and a decrease in the rates of operative mortality.

PMID- 11570052
TI  - [An analysis of medical expenses of outpatient service for the elderly at one
      health insurance society in Fukuoka prefecture--focused on medical service and
      concentration of medical expenses].
AB  - To determine the best way to reduce medical expenses of the elderly, we analyzed
      the aged outpatients' receipts covered by the Health and Medical Service Law for
      the Aged at one health insurance society in Fukuoka prefecture. We used 312
      medical receipts during July, 1997. The proportion of frequency of each medical
      service was 89.7% for medications, 45.8% for laboratory tests and 26.3% for
      procedures. The proportion of expenses of each medical service was 38.3% for
      medications, 20.0% for examinations and 12.1% for laboratory tests. Medication is
      considered as one of the main causes of increasing medical expenses. As a result
      of multiple regression analysis, the number of consulting days, urinary and
      genital disorder, the number of diseases, home care, laboratory tests and
      prescriptions for outside pharmacies were detected as statistically significant
      factors associated with medical expenses. There was a concentration of medical
      expenses, i.e. about 10% of higher rank receipts consumed around 40% of total
      outpatients' expenses and included 6 of 10 home medical care receipts. One of the
      causes of expensive outpatients' medical expenses was medication. The separation
      of dispensary and prescription of drugs does not contribute to the reduction of
      medical expenses. In the higher rank of the expenses group, compared with the
      lower rank of the expenses group, the consultation days were longer, the number
      of diseases was greater and the proportions of expenses for procedures and home
      care were larger. Medical expenditures for patients receiving home medical care
      were higher than those of others, but home care should be compared with
      admissions. Because the insurance societies are now facing financial difficulties
      in Japan, analyzing the data of medical receipts is very important. During our
      analysis, we had to make an enormous effort to combine two data sources, because
      the receipts were made separately by clinics and pharmacies. It is strongly
      suggested that a computerized information system with a standardized format for
      clinics and pharmacies be developed.

PMID- 11570053
TI  - [A family with multiple thrombosis including infancy occurrence].
AB  - Since the first patient with antithrombin deficiency was reported, various
      hereditary thrombophilia have been discovered. However, we experienced a family
      line of multiple thrombosis in which known hereditary thrombophilia were all
      refuted. Case 1 died of inferior vena cava thrombosis at the age of 56 days. Case
      2, the elder sister of Case 1, developed deep vein thrombosis of the left leg at
      age 2. She was started on warfarin but contracted deep vein thrombosis of the
      right leg at the age of 7. In the family of these cases there have been another
      five cases of thrombosis, spanning three generations, giving a total of seven
      cases. Six of the cases developed at an early age, below 50 years. Antithrombin,
      protein C, protein S, heparin cofactor II, soluble thrombomodulin, plasminogen,
      alpha 2 plasminogen inhibitor, and tissue factor pathway inhibitor were measured
      but there were no abnormalities, nor was there any resistance to activated
      protein C. The onset of thrombosis in this family is becoming younger with the
      passing of generations, and clinical symptoms have been showing a worsening
      tendency.

PMID- 11570054
TI  - [Making a low cost IPSec router on Linux and the assessment for practical use].
AB  - We installed Linux and FreeS/WAN on a PC/AT compatible machine to make an IPSec
      router. We measured the time of ping/ftp, only in the university, between the
      university and the external network. Between the university and the external
      network (the Internet), there were no differences. Therefore, we concluded that
      CPU load was not remarkable at low speed networks, because packets exchanged via
      the Internet are small, or compressions of VPN are more effective than encoding
      and decoding. On the other hand, in the university, the IPSec router performed
      down about 20-30% compared with normal IP communication, but this is not a
      serious problem for practical use. Recently, VPN machines are becoming cheaper,
      but they do not function sufficiently to create a fundamental VPN environment.
      Therefore, if one wants a fundamental VPN environment at a low cost, we believe
      you should select a VPN router on Linux.

PMID- 11570055
TI  - JCAHO's disease-specific care program.

PMID- 11570056
TI  - Latex allergies. Safety issue for patients and employees.

PMID- 11570057
TI  - Diabetes care. Collaboration produces evidence-based performance measurements.

PMID- 11570059
TI  - HIPAA protects patients' rights to privacy.

PMID- 11570058
TI  - JCAHO update. Information management (IM).

PMID- 11570060
TI  - Re-examining blood use to improve quality care.
AB  - With escalating costs and restrictions on who can donate blood, the issue of
      blood use among health care facilities has managed to attract recent headlines.
      The basic concerns over blood use, availability, safety, and quality are not
      necessarily new or unique in this day and age. However, finding better ways to
      meet these ongoing challenges--through better standardization and improved data-
      have been slower in coming than in other sectors of the health care arena. But,
      times are changing. Examples are emerging of what can be done by hospitals,
      health systems, health plans, and other providers to achieve quality care--even
      when faced with limited supplies of blood and blood products. And, with the
      tensions arising between supply and demand, hospitals also are beginning to pay
      closer attention to bloodless--or transfusion-free--medicine and surgery.

PMID- 11570061
TI  - Switching meds: from protease inhibitors to non-nukes.

PMID- 11570062
TI  - Some women may be at high risk for anal cancer.

PMID- 11570063
TI  - Triple nuke therapy--results after one year.

PMID- 11570064
TI  - Nukes linked to fat wasting.

PMID- 11570065
TI  - DHEA--background.

PMID- 11570066
TI  - Changes in DHEA levels in people taking anti-HIV therapy.

PMID- 11570067
TI  - DHEA for depression?

PMID- 11570068
TI  - DHEA--cautions and concerns.

PMID- 11570070
TI  - Canadian researchers study "immune healing".

PMID- 11570069
TI  - Kaletra approved in Canada.
AB  - On March 9, 2001, Health Canada granted permission to Abbott Laboratories for the
      sale of Kaletra (a combination of protease inhibitors lopinavir and ritonavir),
      formerly known as ABT-378/r, for the treatment of HIV infection in adults and
      children six months or older. Kaletra was approved for sale in the U.S. in
      September 2000.

PMID- 11570071
TI  - St. John's wort extract found not helpful for hepatitis C.

PMID- 11570072
TI  - Are deaths due to liver damage becoming more common?

PMID- 11570073
TI  - St. John's wort found to lower nevirapine levels.

PMID- 11570074
TI  - 8th Conference on Retroviruses and Opportunistic Infections.

PMID- 11570075
TI  - Amping amprenavir with ritonavir.

PMID- 11570076
TI  - Wanted: meds to attack macs.

PMID- 11570077
TI  - Immune boosters. Focus on the immune system.

PMID- 11570078
TI  - New treatment guidelines available.

PMID- 11570079
TI  - Stages in HIV infection: when to start treatment.

PMID- 11570080
TI  - Impact of HAART in early HIV infection.

PMID- 11570081
TI  - Impact of HAART late in HIV infection.

PMID- 11570082
TI  - Too much iron can cause problems.

PMID- 11570083
TI  - Causes of death shift over time.

PMID- 11570084
TI  - Transplanted livers and kidneys for HIV+ people.

PMID- 11570086
TI  - I think I CAM: use of complementary and alternative medicine by PHAs.

PMID- 11570085
TI  - Garlic supplements found to lower saquinavir levels.

PMID- 11570087
TI  - Put this in your pipe and smoke it: medicinal marijuana study.

PMID- 11570088
TI  - Fusion inhibitors: T-20 and T-1249.

PMID- 11570090
TI  - Choosing which nuke to use first.

PMID- 11570089
TI  - Switching from protease inhibitors to the non-nuke efavirenz.

PMID- 11570091
TI  - Once-daily therapy--results after one year.

PMID- 11570092
TI  - A new protease inhibitor from Bristol-Myers Squibb.

PMID- 11570093
TI  - From grapefruit juice to ritonavir.

PMID- 11570094
TI  - Ritonavir and indinavir one year later.

PMID- 11570095
TI  - Using ritonavir with indinavir in cases of virologic failure.

PMID- 11570096
TI  - Merck pushes the envelope with once-daily indinavir.

PMID- 11570097
TI  - Kaletra versus nelfinavir.

PMID- 11570098
TI  - Evolution of transport proteins.

PMID- 11570099
TI  - Mechanisms of apoptosis repression.

PMID- 11570100
TI  - Enzyme and pathway engineering for suicide gene therapy.

PMID- 11570101
TI  - Deconstructing a conserved protein family: the role of MCM proteins in eukaryotic
      DNA replication.

PMID- 11570102
TI  - Expression of foreign genes in the yeast Pichia pastoris.

PMID- 11570103
TI  - Protein splicing and its applications.

PMID- 11570104
TI  - Global transcript expression profiling by Serial Analysis of Gene Expression
      (SAGE).

PMID- 11570105
TI  - Cytokine activation of transcription.

PMID- 11570106
TI  - Enzymatic approaches to glycoprotein synthesis.

PMID- 11570107
TI  - Vector design and development of host systems for Pseudomonas.

PMID- 11570108
TI  - Genetic and biochemical studies on the assembly of an enveloped virus.

PMID- 11570109
TI  - Exercise in the reduction of cardiovascular events. Lessons from epidemiologic
      trials.
AB  - In conclusion, much has been learned about the effects of exercise in reducing
      events in those with CHD. Some data are confusing, however, and some gaping holes
      exist in our understanding. Hopefully, new data forthcoming in the next 5 to 10
      years will clear up this picture significantly. Meanwhile, cardiovascular
      exercise, coupled with other risk factor reduction, has been firmly established
      as a lifesaving and life-improving tool in those who have developed
      manifestations of CHD.

PMID- 11570110
TI  - Effects of exercise training on vascular function and myocardial perfusion.
AB  - It has long been unclear how exercise training improves myocardial perfusion in
      patients with stable CAD. Regression of coronary atherosclerosis and collateral
      formation have been favorite theories; however, angiographic techniques have so
      far failed to document any significant increase in coronary collaterals at rest.
      Although net regression of stenotic lesions may be achieved in high-intensity
      exercise training, it is unlikely that it causes the significant improvement in
      myocardial perfusion that is seen much earlier than plaque regression. The novel
      tools to examine coronary endothelial function in vivo and in vitro have now made
      it clear that exercise training enhances myocardial perfusion by increasing both
      eNOS and ecSOD expression, which attenuates the premature breakdown of NO by ROS.
      These increases in local NO production and half-life improve endothelium
      dependent vasodilation in response to flow or acetylcholine. These functional
      changes will occur rather rapidly after the initiation of an exercise training
      program, although no studies are available on their precise time course. Anatomic
      changes, such as augmentation of the capillary bed and slowing of the progression
      of coronary atherosclerosis, may require more extended periods of training (Fig.
      4). Recently, first reports about a possible association between endothelial
      dysfunction and the frequency of clinical events has been documented. Further
      prospective studies are needed to establish whether endothelial dysfunction is
      just an indicator of plaque instability or an independent prognostic marker. If
      it turns out to be the latter, exercise training may be promoted from a
      symptomatic intervention to a preventive strategy with long-term prognostic
      benefits.

PMID- 11570111
TI  - Exercise and autonomic function in health and cardiovascular disease.
AB  - Autonomic nervous system activity contributes to the regulation of cardiac output
      during rest, exercise, and cardiovascular disease. Measurement of HRV has been
      particularly useful in assessing parasympathetic activity, while its utility for
      assessing sympathetic function and overall sympathovagal balance remains
      controversial. Studies have revealed that parasympathetic tone dominates the
      resting state, while exercise is associated with prompt withdrawal of vagal tone
      and subsequent sympathetic activation. Conversely, recovery is characterized by
      parasympathetic activation followed by sympathetic withdrawal, although
      clarification of the normal trajectory and autonomic basis of heart rate decay
      following exercise is needed. Abnormalities in autonomic physiology--especially
      increased sympathetic activity, attenuated vagal tone, and delayed heart rate
      recovery--have been associated with increased mortality. Exercise training is
      associated with a relative enhancement of vagal tone, improved heart rate
      recovery after exercise, and reduced morbidity in patients with cardiovascular
      disease. However, whether exercise training leads to reduced mortality in this
      population because of its ability to specifically modulate autonomic function is
      unknown at the present time. Although the results of a recent randomized study in
      patients with CHF and a meta-analysis in the setting of a recent myocardial
      infarction determined that exercise training leads to improved outcomes in these
      populations, neither study measured autonomic function. Improved autonomic
      function due to exercise training is a promising rationale for explaining
      improvements in outcome, although more research is needed to confirm this
      hypothesis.

PMID- 11570112
TI  - Exercise and thrombosis.
AB  - Long-term moderate or strenuous physical activity is associated with a
      considerable reduction in cardiovascular morbidity and mortality in primary and
      secondary prevention. Various mechanisms, including changes in lipids, lifestyle
      habits, and other positive physiologic effects, have been suggested to mediate
      these beneficial effects. In addition, the hemostatic and fibrinolytic systems
      appear to play an important role. Fibrinogen has been convincingly shown to be an
      independent cardiovascular risk factor. Other hemostatic and fibrinolytic
      parameters that are predictive of coronary events include factor VII, platelet
      hyperreactivity, plasminogen-activator inhibitor 1 (PAI-1), and tissue
      plasminogen activator. The effects of exercise on fibrinogen have been
      intensively studied. Several randomized controlled trials, various other
      intervention studies and a large number of population-based cross-sectional
      studies all found an inverse relationship between measures of sport activity or
      leisure activity and plasma fibrinogen. The magnitude of the effect reported
      might be associated with a sizeable reduction in major coronary events.
      Relatively few data are available on the effects of endurance exercise on markers
      of the fibrinolytic system, with inconsistent results. Acute exercise leads to a
      transient activation of the coagulation system, which is accompanied by an
      increase in the fibrinolytic capacity in healthy subjects. Patients with ischemic
      heart disease, who cannot increase their fibrinolytic potential, however, may be
      at considerable risk for acute ischemic events if they are exposed to
      unaccustomed strenuous physical exertion.

PMID- 11570113
TI  - Exercise electrocardiogram testing and prognosis. Novel markers and predictive
      instruments.
AB  - Ample evidence now exists supporting the use of the exercise test primarily for
      prognostic, as opposed to diagnostic, purposes. Although limitations must be
      recognized, the Duke exercise treadmill score, the chronotropic response to
      exercise, and heart rate recovery appear to function as powerful and independent
      predictors of risk. With the possible exception of exercise-induced ischemia, as
      manifested by the ST-segment and angina components of the Duke exercise treadmill
      score, exercise predictors of risk are not clearly modifiable. Nonetheless, they
      are clinically quite useful since they may well identify patients who are or are
      not likely to gain benefit from further testing and aggressive therapies. How so?
      The "plain old" exercise treadmill test makes it possible to easily, safely, and
      inexpensively identify a large group of patients who are at low risk for death or
      major cardiac events. For this reason alone, the predictive instruments described
      in this article should be routinely incorporated into clinical practice. It makes
      no sense to perform expensive and potentially risky diagnostic tests, prescribe
      polypharmacy, or institute invasive therapeutic procedures in patients who are
      already at low risk. As an example, Weiner and colleagues found that coronary
      bypass grafting only benefited CASS registry patients who had a high-risk
      exercise test result. Future research will be needed to further refine risk
      stratification with the exercise test, and determine how best to use adjunctive
      imaging studies and to reduce risk among patients with prognostically important
      findings.

PMID- 11570114
TI  - Exercise testing in cardiac rehabilitation. Exercise prescription and beyond.
AB  - The prescription of exercise, either as a part of a formal exercise training
      program or as a means to increase physical activity in general, has been and will
      remain a primary component of cardiac rehabilitation and secondary prevention
      programming. Wherever possible, this prescription should be based on a recent
      exercise test that documents the cardiac patient's functional capacity, cardiac
      and hemodynamic responses to exercise, and signs and symptoms associated with
      exertion. Clearly the prescription of exercise and suggestions for increasing
      levels of physical activity must be based on accepted principles of exercise
      physiology and expected training responses. Nonetheless, the art of exercise
      prescription should guarantee flexible methodologies to meet the specific needs
      of each individual patient. Although the patient must accept ultimate
      responsibility for participation, the clinician bears the burden of continually
      attempting to reinforce the importance of increasing caloric expenditure and
      motivating patients to initiate and commit to long-term participation in a safe
      and appropriately designed program of exercise and increasing physical activity.

PMID- 11570115
TI  - Exercise testing with gas exchange analysis.
AB  - The value of ventilatory gas exchange techniques during exercise testing,
      including improved precision and a greater yield of clinically useful
      information, is underscored by a growing body of literature. With technological
      advances available in the current metabolic systems, the test can be performed
      with minimal inconvenience to the patient and a minimal time commitment on the
      part of the operator. Gas exchange techniques have many applications among
      patients with cardiovascular and pulmonary disease, including the assessment of
      therapeutic interventions, a better understanding of the pathophysiology of
      exercise intolerance, and evaluation of disability. Recent studies suggest that
      the added precision provided by this technology has important prognostic utility.
      A cardiopulmonary exercise test can supplement other clinical and exercise test
      information when precision is important, when the patient's symptoms are mixed,
      or when it is unclear why the patient was referred for testing.

PMID- 11570116
TI  - Physical activity and exercise training prescriptions for patients.
AB  - The dominant outcome from exercise prescription is an increase in various markers
      of exercise capacity. A very large group of studies have demonstrated that the
      VO2max is increased in response to exercise performed according to well-accepted
      principles of exercise prescription. Other markers of exercise capacity, such as
      the VT, also improve substantially following exercise training. Finally,
      improvement in exercise capacity is generally related to improved quality of
      life, particularly in patients with exercise capacity limited by various disease
      processes. Beyond the specific physiologic gains from training, exercise
      contributes to a better overall clinical outcome. Although there are few data
      conclusively demonstrating that exercise independently causes favorable changes
      in other risk factors, it should be recognized that exercise can contribute
      indirectly to modulation of other risk factors. Exercise represents positive
      health advice. Since most of our other recommendations to patients are in the
      nature of negative advice (e.g., don't smoke, don't eat high-fat foods), and
      since people are infamous for ignoring negative advice, the value of using a
      positive recommendation that may indirectly lead the patient to discontinue bad
      behaviors can hardly be overstated.

PMID- 11570117
TI  - Exercise in weight management of obesity.
AB  - Obesity is a chronic metabolic disorder associated with CVD and increased
      morbidity and mortality. When the BMI is > or = 30 kg/m2, mortality rates from
      all causes, and especially CVD, are increased by 50% to 100%. There is strong
      evidence that weight loss in overweight and obese individuals improves risk
      factors for diabetes and CVD. Additional evidence indicates that weight loss and
      the associated diuresis reduce blood pressure in both overweight hypertensive and
      nonhypertensive individuals, reduce serum TG levels, increase high-density
      lipoprotein cholesterol levels, and may produce some reduction in low-density
      lipoprotein cholesterol concentrations. Of interest, even if weight loss is
      minimal, obese individuals showing a good level of cardiorespiratory fitness are
      at reduced risk for cardiovascular mortality than lean but poorly fit subjects.
      Insulin and catecholamines have pronounced metabolic effects on human adipose
      tissue metabolism. Insulin stimulates LPL and inhibits HSL; the opposite is true
      for catecholamines. There is regional variation in adipocyte TG turnover favoring
      lipid mobilization in the visceral fat depots and lipid storage in the peripheral
      subcutaneous sites. The hormonal regulation of adipocyte TG turnover is altered
      in obesity and is most marked in central obesity. There is resistance to insulin
      stimulation of LPL; however, LPL activity in fasted obese subjects is increased
      and remains so following weight reduction. Catecholamine-induced lipolysis is
      enhanced in visceral fat but decreased in subcutaneous fat. Numerous adaptive
      responses take place with physical training. These adaptations result in a more
      efficient system for oxygen transfer to muscle, which is now able to better
      utilize the unlimited lipid stores instead of the limited carbohydrate reserves
      available. In addition, the reduced adipose tissue mass represents an important
      mechanical advantage, allowing better long-term work. Gender differences have
      been reported in the adaptation of adipose tissue metabolism to aerobic exercise
      training. Physical training helps counteract the permissive and affluent
      environment that predisposes reduced-obese subjects to regain weight. An exercise
      program using weight resistance modalities may also be included safely, and it
      improved program retention in a multidisciplinary weight management program that
      was designed for obese children. Thirty to 45 minutes of physical activity of
      moderate intensity, performed 3 to 5 days a week, should be encouraged. All
      adults should set a long-term goal to accumulate at least 30 minutes or more of
      moderate-intensity physical activity on most, and preferably all days. Public
      health interventions promoting walking are likely to be the most successful.
      Indeed, walking is unique because of its safety, accessibility, and popularity.
      It is noteworthy that there is a clear dissociation between the adaptation of
      cardiorespiratory fitness and the improvements in the metabolic risk profile that
      can be induced by endurance training programs. It appears that as long as the
      increase in energy expenditure is sufficient, low-intensity endurance exercise is
      likely to generate beneficial metabolic effects that would be essentially similar
      to those produced by high-intensity exercise. The clinician should therefore
      focus on the improvement of the metabolic profile rather than on weight loss
      alone. Realistic goals should be set between the clinician and the patient, with
      a weight loss of approximately of 0.5 to 1 pound per week. It should be kept in
      mind that since it generally takes years to become overweight or obese, a weight
      loss pattern of 0.5 or 1 pound per week will require time and perseverance to
      reach the proposed target. However, the use of physical activity as a method to
      lose weight seems inversely related to patients' age and BMI and directly related
      to the level of education. Thus, public health interventions helping these groups
      to become physically active remain a challenge and further emphasize the
      importance of the one-on-one interaction between the clinician/health care
      professional with the obese individual "at risk" of CVD. This notion is critical,
      as it has been shown that less than half of obese adults have reported being
      advised to lose weight under the guidance of health care professionals.

PMID- 11570118
TI  - Exercise in the treatment of lipid disorders.
AB  - As a result of scientific evaluation, we know that exercise has a positive impact
      on the lipid and lipoprotein profile, and we have a greater understanding for the
      necessary amount of exercise needed to cause these changes. In the case of
      hyperlipidemic disorders, we know the primary means for intervention is
      pharmacological, and that diet, weight loss, and exercise are viewed as
      adjunctive therapies. Because much is known about the exercise training-induced
      plasma lipid and lipoprotein modifications as well as the lipoprotein enzyme
      changes, future research should continue to focus on the molecular basis for
      these changes. For example by knowing a person's apo E genotype, we gain better
      comprehension as to why some individuals respond to exercise, while others do
      not. Another area for further investigation is the assessment of drug and
      exercise interaction. Presently, little is known regarding the use of lipid
      lowering drugs and the impact of exercise. Finally, these investigations could
      provide new insights for better understanding the exercise CAD protective
      effects. The future challenge is to better understand the impact that regular
      exercise participation has in optimizing the lipid and lipoprotein profile with
      individuals with special lipid disorders.

PMID- 11570119
TI  - Exercise and diabetes.
AB  - As rates of diabetes mellitus and obesity continue to increase, physical activity
      continues to be a fundamental form of therapy. Exercise influences several
      aspects of diabetes, including blood glucose concentrations, insulin action and
      cardiovascular risk factors. Blood glucose concentrations reflect the balance
      between skeletal muscle uptake and ambient concentrations of both insulin and
      counterinsulin hormones. Difficulties in predicting the relative impact of these
      factors can result in either hypoglycemia or hyperglycemia. Despite the variable
      impact of exercise on blood glucose, exercise consistently improves insulin
      action and several cardiovascular risk factors. Beyond the acute impact of
      physical activity, long-term exercise behaviors have been repeatedly associated
      with decreased rates of type 2 diabetes. While exercise produces many benefits,
      it is not without risks for patients with diabetes mellitus. In addition to
      hyperglycemia, from increased hepatic glucose production, insufficient insulin
      levels can foster ketogenesis from excess concentrations of fatty acids. At the
      opposite end of the glucose spectrum, hypoglycemia can result from excess glucose
      uptake due to either increased insulin concentrations, enhanced insulin action or
      impaired carbohydrate absorption. To decrease the risk for hypoglycemia, insulin
      doses should be reduced prior to exercise, although some insulin is typically
      still needed. Although precise risks of exercise on existing diabetic
      complications have not been well studied, it seems prudent to consider the
      potential to worsen nephropathy or retinopathy, or to precipitate musculoskeletal
      injuries. There is more substantive evidence that autonomic neuropathy may
      predispose patients to arrhythmias. Of clear concern, increased physical activity
      can precipitate a cardiac event in those with underlying CAD. Recognizing these
      risks can prompt actions to minimize their impact. Positive actions that are part
      of exercise programs for diabetic patients emphasize SMBG, foot care and
      cardiovascular functional assessment. SMBG provides critical information on the
      impact of exercise and is recommended for all patients before, during and after
      exercise. More frequent monitoring (and for longer periods following exercise) is
      recommended for those with hypoglycemia unawareness or those performing high
      intensity exercise. Preventing the sequelae of an exercise-induced severe
      hypoglycemic reaction can be as simple as carrying glucose tablets or gel, a
      diabetic identification bracelet or card, or exercising with an individual who is
      aware of the circumstances. In addition to blood glucose concentrations, proper
      foot care is critical to people with diabetes who exercise and includes
      considering type of shoe, type of exercise, inspection of skin surfaces and
      appropriate evaluation and treatment of lesions (calluses and others). Those with
      severe neuropathy can consider alternatives to weight-bearing exercises.
      Precipitation of clinical CAD is of great concern for all diabetic patients
      participating in exercise activities. Although a sufficiently sensitive and
      specific screening test for coronary disease has not been identified, those
      planning an exercise program of moderate intensity or greater should be
      evaluated. Initial cardiac assessment should include exercise testing as well as
      identifying risk for autonomic neuropathy. In addition to noting maximal heart
      rate and blood pressure as well as ischemic changes, exercise tolerance testing
      can identify anginal thresholds and patients with asymptomatic ischemia. Those
      without symptoms should be counseled regarding target pulse rates to avoid
      inducing ischemia. Ischemic changes need to be evaluated for either further
      diagnostic testing or pharmacological intervention. For patients with diabetes
      mellitus, the overall benefits of exercise are clearly significant. Clinicians
      and patients must work together to maximize these benefits while minimizing risks
      for negative consequences. Identifying and preventing potential problems
      beforehand can reduce adverse outcomes and promote this important approach to
      healthy living.

PMID- 11570120
TI  - Exercise as hypertension therapy.
AB  - In conclusion, the findings of most recent studies show that moderate-intensity
      aerobic exercise training can lower BP in patients with stage 1 and 2 essential
      hypertension. The average reduction in BP is 10.5 mm Hg for systolic and 7.6 mm
      Hg for diastolic BP. The reductions do not appear to be gender- or age-specific.
      Significant reductions in BP and LVH regression in patients with stage 3
      hypertension have also been reported following aerobic exercise training.
      Resistance training exercise has not consistently shown to significantly lower BP
      and is not recommended as the only form of exercise for hypertensive patients.
      The exercise training program for optimal benefits should consist of 3 to 5 times
      per week, 30 to 60 minutes per session, at 50% to 80% of PMHR. However, exercise
      programs should be individualized to meet the patient's needs and abilities.
      Exercise intensity and duration should be manipulated to promote a safe and
      effective antihypertensive program. Initially, the exercise intensity should be
      low and the duration short. Both intensity and duration should progressive
      increase over a period of weeks until the desired goal, is achieved. The rate of
      progression must be tailored to meet individual patient needs and abilities. The
      exercise program for overweight or obese hypertensive patients should aim to
      promote a caloric expenditure of 300 to 500 Kcal per day and 1000 to 2000 Kcal
      per week. Such an approach, combined with a prudent diet, is likely to reduce
      body weight. The mechanisms mediating exercise-induced BP reduction are poorly
      understood. BP reductions appear to be independent of changes in body weight or
      body composition. There are also no indications of age- or gender-related
      differences in BP response to exercise. The use of ambulatory blood pressure
      measuring devices in exercise studies is not extensive. The few studies available
      indicate a more moderate reduction in BP than that reported by casual
      observations.

PMID- 11570121
TI  - Exercise and heart failure.
AB  - Chronic heart failure (CHF) is a common condition with a poor prognosis, commonly
      associated with poor exercise tolerance and debilitation symptoms despite optimal
      modern therapy. Recent investigations have shown that the degree of exercise
      limitation may be related to pathophysiological changes that occur systemically
      in the patient with CHF. Exercise training in carefully selected stable patients
      with heart failure has been shown to be safe to correct many of these
      pathophysiological changes in the periphery and to lead to worthwhile
      improvements in exercise capacity. Recent studies have suggested a possible
      improvement in mortality and morbidity with exercise training in this patient
      group. This article discusses the factors limiting exercise capacity in CHF and
      reviews the controlled clinical trial of exercise testing in this condition.

PMID- 11570122
TI  - Exercise rehabilitation of older patients with cardiovascular disease.
AB  - As the population of elderly patients with cardiovascular disease continues to
      increase, much research needs to be done with the goal of maintaining physical
      functioning and personal independence in this population. It is of particular
      importance to determine whether training programs can improve physical
      functioning in the most severely disabled older coronary patients. Effects of
      cardiac rehabilitation programs on other outcome measures, including psychosocial
      outcomes, lipid levels, insulin levels, and body composition require better
      study. Finally, the economic benefits of cardiac rehabilitation in the older
      coronary patients has received little attention, although early reports are
      promising. In summary, the older population with coronary disease is
      characterized by high rates of disability. Exercise training has been
      demonstrated to be safe and to improve strength, aerobic fitness capacity,
      endurance and physical function. It remains to be seen whether exercise training
      can reverse or prevent disability in a broad population of older patients with
      cardiovascular disease. If successful, cardiac rehabilitation programs will pay
      great medical, social, and economic dividends in this population.

PMID- 11570123
TI  - Medical treatment of canine pituitary-dependent hyperadrenocorticism (Cushing's
      disease).
AB  - Pituitary-dependent hyperadrenocorticism (Cushing's disease) is a relatively
      common endocrine disorder of middle- to old-age dogs. Three treatments commonly
      used in the management of pituitary-dependent Cushing's disease in dogs include
      mitotane, ketoconazole, and L-deprenyl. These medications are associated with the
      potential of different side effects and expense, but all can produce satisfactory
      results in dogs with this disease. The choice of treatment for a given dog
      depends on the severity of the dog's disease, as well as clinician and client
      preferences. This article reviews the indications and adverse effects associated
      with each of these three drugs, as well as the treatment protocols commonly used
      in treating dogs with hyperadrenocorticism.

PMID- 11570124
TI  - Hypophysectomy as a treatment for canine and feline Cushing's disease.
AB  - The microsurgical technique of transsphenoidal hypophysectomy performed with the
      dogs and cats positioned in sternal recumbency enables the treatment of Cushing's
      disease, independent of skull type, in a safe and effective manner. In dogs, the
      short-term survival rate after hypophysectomy is comparable to that after
      treatment with o,p'-DDD, whereas the recurrence rate in this period is lower.
      When the surgeon has gone through a learning curve, the results of the 1- to 3
      year follow-up interval may be better than those after adrenocorticolysis with
      o,p'-DDD. CT enables assessment of localization and size of the pituitary before
      surgery. In general, dogs with Cushing's disease and normal-sized pituitaries or
      moderately enlarged pituitaries (up to 12 mm in diameter) are suitable candidates
      for transsphenoidal surgery. In dogs with larger pituitary tumors and tumor
      extension rostrally or caudally over the dorsum sellae, transsphenoidal debulking
      surgery may be only a palliative treatment. The main complications are
      postoperative hypernatremia, keratoconjunctivitis sicca, diabetes insipidus, and
      secondary hypothyroidism. In cats, special attention should be paid to closure of
      the soft palate. The neurosurgeon must be familiar with these complications so as
      to recognize them as early as possible and to treat them immediately and
      effectively. It is concluded that microsurgical transsphenoidal hypophysectomy in
      dogs and cats with Cushing's disease is an effective method of treatment.

PMID- 11570125
TI  - Update on the diagnosis and treatment of disorders of calcium regulation.
AB  - The availability of PTH, iCa, PTHrP, and 25OHD assays for evaluation of calcium
      abnormalities in companion animals has been well received [table: see text] by
      clinicians and diagnosticians. Use of these assays has heightened awareness that
      some of these disorders are more common than originally thought. Also, there is
      added insight of alterations of calcium homeostasis as a consequence of other
      illness or environmental factors such as diet. Animal counterparts of other
      disorders of calcium metabolism in people are likely to be identified, and use of
      these assays should play a significant role. As already emphasized, the
      foundation of using [table: see text] these assays is first assessing whether the
      calcium abnormality is of a parathyroid-dependent or parathyroid-independent
      classification.

PMID- 11570126
TI  - Feline endocrinology update.
AB  - This article highlights the advances in feline endocrinology, excluding diabetes
      mellitus and hyperadrenocorticism, which have recently been reviewed elsewhere.
      The goal will be to provide clinically relevant information regarding
      pathogenesis, diagnosis, and treatment options for these feline endocrine
      disorders.

PMID- 11570127
TI  - Endocrine tumors.
AB  - Because of the diverse nature of endocrine organs, and their vast range of
      physiologic functions, endocrine tumors encompass a wide range of origination
      sites and disease entities. The clinical picture of affected individuals is
      highly dependent on the tissue of origin, and the presence or absence of
      functional hormone secretions. Identification, localization, and therapeutic
      strategies, as well as prognosis can vary greatly. Many endocrine tumors have
      been described in human as well as veterinary patients. This article focuses on
      endocrine tumors of dogs and cats. Various tumors affecting the pancreas,
      thyroid, parathyroid, adrenal and pituitary glands are described, including
      insulinoma, gastrinoma, glucagonoma, and thyroid carcinoma, as well as
      parathyroid hormone- and growth hormone-secreting tumors. The syndrome of
      multiple endocrine neoplasia is also described.

PMID- 11570128
TI  - Polyuria and polydipsia. Diagnostic approach and problems associated with patient
      evaluation.
AB  - Primary disorders of water balance (central diabetes insipidus [DI], nephrogenic
      DI, and psychogenic polydipsia) should always be considered in the differential
      diagnosis of polyuria and polydipsia. In general, animals with these disorders
      have only one laboratory abnormality: a low urine specific gravity. In most
      instances, the more common causes of polyuria and polydipsia (e.g.,
      hyperadrenocorticism, chronic renal failure, pyelonephritis, pyometra) have
      specific and obvious abnormalities associated with the complete blood cell count,
      the serum chemistry profile, and urinalysis. In some cases, however, a low urine
      specific gravity may be the only abnormality associated with these more common
      findings. The workup for polyuria and polydipsia can be tedious, time-consuming,
      expensive, confusing, and not without significant patient morbidity, especially
      in those cases with normal or near-normal blood work. This article focuses on the
      diagnostic approach and problems associated with diagnostic testing in patients
      with disorders of water balance.

PMID- 11570129
TI  - Diagnosis of diabetes mellitus in cats and dogs.
AB  - This article describes the clinical presentation of diabetes mellitus in cats and
      dogs, including the types of diabetes, signalment, history, physical examination
      findings, and laboratory diagnosis. Newer diagnostic tests such as serum
      fructosamine concentrations and arginine response rate are also briefly
      discussed.

PMID- 11570130
TI  - Management of canine diabetes.
AB  - The majority of diabetic dogs appear to have a form of type 1 diabetes analogous
      to the latent autoimmune diabetes of adults (LADA) in humans. Evidence of acute
      or chronic pancreatitis occurs in about 40% of diabetic dogs. Blindness caused by
      cataract formation eventually occurs in the majority of diabetic dogs and is not
      dependent on glycemic control. Insulin is the mainstay of therapy for diabetic
      dogs, and a conservative approach to insulin therapy is crucial. Most diabetic
      dogs require twice-daily dosing with lente or NPH insulin to adequately control
      their clinical signs. The diet fed should primarily be palatable and
      nutritionally balanced. Improved glycemic control may be achieved in some dogs if
      the diet contains increased insoluble fiber.

PMID- 11570131
TI  - Management of feline diabetes mellitus.
AB  - Up to one quarter of diabetic cats can be well controlled with oral hypoglycemic
      drugs, although at least 75% require insulin therapy. Most available insulins
      provide good clinical control but only moderate glycemic control. Because mild to
      moderate hyperglycemia is well tolerated by cats receiving insulin but
      hypoglycemia can be life threatening, conservative insulin dosing is recommended.
      Clinical signs and water intake indicate whether a dose adjustment is required,
      but serial blood glucose measurements are usually needed to determine the
      direction of the adjustment. Starting doses of 0.3 to 0.5 IU/kg administered
      twice daily (rounded down to the nearest whole unit) are usually safe. Dose
      adjustments should not exceed 1 IU per cat every 2 to 4 weeks unless clinical
      hypoglycemia has occurred. Cats with clinical hypoglycemia need to be reassessed
      to see if they are in remission. If not, a 50% to 75% reduction in dose is
      advised. Approximately 30% of cats go into diabetic remission 1 to 4 months after
      an adequate treatment protocol is instituted.

PMID- 11570133
TI  - Conditions associated with canine hypothyroidism.
AB  - Careful review of the literature regarding clinical signs caused by
      hypothyroidism in dogs has shown that some assumptions regarding the relation of
      hypothyroidism to other conditions are based on anecdotal evidence. Cutaneous
      manifestations are present in most hypothyroid dogs, but the specific
      abnormalities and breed variations remain to be clearly defined. Decreased
      metabolic rate manifested by obesity and lethargy is also common. Neurologic
      manifestations, although uncommon, clearly occur in hypothyroid dogs. Cardiac
      abnormalities seem to be common, but their clinical significance is questionable.
      The only consistent hematologic abnormality that occurs in hypothyroid dogs is
      anemia; evidence for acquired von Willebrand's disease or other bleeding
      disorders is negligible. Reproductive dysfunction secondary to hypothyroidism is
      unlikely to occur in male dogs, and there is no evidence to support abnormalities
      in female dogs. The relation of megaesophagus, laryngeal paralysis, ocular
      abnormalities, and gastrointestinal disorders with hypothyroidism remains to be
      established. Future research into canine hypothyroidism may serve to convert
      dogma into a more clear understanding of the manifestations and pathophysiologic
      findings of this common endocrinopathy.

PMID- 11570132
TI  - Lymphocytic thyroiditis.
AB  - Lymphocytic thyroiditis is a common canine condition that can lead to functional
      hypothyroidism. It is associated with more than 50% of cases of canine
      hypothyroidism. Evidence in human beings and experimental situations suggests
      that it is a disease of defective immunoregulation, but specific investigation of
      the molecular pathogenesis of the naturally occurring disease in dogs has not yet
      been carried out. The condition is heritable in those breeds that have been
      studied, and progression to hypothyroidism, if it occurs, can be slow. Factors
      that influence the progression from subclinical thyroiditis to hypothyroidism in
      dogs are still to be identified, but excessive iodine intake is an important
      factor in other species.

PMID- 11570134
TI  - Diagnosis of canine hypothyroidism. Perspectives from a testing laboratory.
AB  - The most common sample received by our endocrine testing laboratory is submitted
      for the diagnosis of hypothyroidism in a dog. The current tests most frequently
      employed in our laboratory for thyroid evaluation in dogs are total T4, free T4
      by dialysis, and canine TSH measurement. Each test has strengths and weaknesses
      and suffers from the possibility of both false positive and false negative
      results. This article provides a working description of each test and an approach
      to interpretation of results. Other tests that are less commonly used are also
      discussed. Examples of interpretation of test results in individual hypothyroid
      suspect dogs are presented for illustration.

PMID- 11570135
TI  - Feline hyperthyroidism. Diagnostics and therapeutics.
AB  - Today, hyperthyroid cats are less symptomatic than those 10 or 15 years ago, and
      early diagnosis impacts the range and severity of the routine clinicopathological
      abnormalities traditionally associated with this disorder. In addition, a greater
      range of tests may be required to confirm a diagnosis as cats may be assessed
      before a serum total T4 concentration exceeds the reference range. Curative
      treatment options may be more desirable in early cases, but renal function may be
      adversely affected by the induction of euthyroidism and should be carefully
      evaluated before treatment.

PMID- 11570136
TI  - Diagnosis of canine hyperadrenocorticism.
AB  - Canine hyperadrenocorticism is one of the most common endocrinopathies in dogs.
      Diagnosis remains difficult in some cases due to factors such as the presence of
      non-adrenal illness and limitations in the tests. Differentiation between the
      pituitary and adrenal forms is important for providing accurate prognostic
      information and delineating treatment options and protocols. This article reviews
      the tests available for diagnosis (screening) and differentiation and evaluates
      their advantages and disadvantages. Recommendations for testing are made.

PMID- 11570137
TI  - Infections in patients with end-stage renal disease. An overview.
AB  - One of the best kept secrets in medicine is the problem of infections in patients
      with end-stage renal disease. The prescription of chronic hemodialysis has not
      reduced the problem of infection; it has only changed the paradigm. Dialysis
      superimposes myriad new problems onto patients with relentless deterioration from
      underlying multisystem disease and poor wound healing. All end-stage renal
      disease and transplant programs require the input from an individual with the
      specialized knowledge of laboratory diagnosis, pharmacokinetics of antibiotics,
      antibiotic choice, antimicrobial resistance, infection control, and infection
      prevention. This article gives an overview of some of the complexities of
      infectious problems experienced by this unique biological model.

PMID- 11570138
TI  - The end-stage renal disease program. Experience with a chronic disease capitated
      health plan.
AB  - The ESRD program has demonstrated the potential for a capitated, disease
      oriented, total care method of patient support. Given both the increasing age and
      complexity of the patient population, not only has the cost per patient decreased
      over the life of the program, but the standardized mortality rates have also
      declined. Technology has bridged the gap and made the relative cost per treatment
      more affordable and science has developed medications and techniques that have
      enhanced both patient comfort and longevity. As more complex patients enter the
      fold of the ESRD program, an increased awareness of enhanced coordination of care
      needs to be recognized.

PMID- 11570139
TI  - Vascular access infections in patients undergoing dialysis with special emphasis
      on the role and treatment of Staphylococcus aureus.
AB  - Access-related infections are the most important causes of the loss of vascular
      access for dialysis. These infections also may lead to devastating consequences,
      including sepsis with multiorgan failure; endocarditis; or metastatic infections
      such as vertebral osteomyelitis, epidural abscess, or endophthalmitis. A small
      percentage of these complications are fatal; overall, dialysis-related
      bloodstream infections are the second leading cause of death in patients
      undergoing hemodialysis, accounting for up to 10% of all deaths, and
      approximately three-fourths of all deaths caused by infection in patients
      undergoing dialysis. Moreover, vascular placement and complications account for
      approximately one fourth of all admissions and hospital days among patients on
      dialysis.

PMID- 11570140
TI  - Infections in patients undergoing peritoneal dialysis.
AB  - Considering experience acquired in the past years, it seems as though physicians
      have reached a plateau in the frequency of peritonitis. A peritonitis rate of 1
      every 2 patient years may be acceptable. Further reduction of this peritonitis
      rate will require inordinately large efforts on all fronts. One will have to
      consider what are the acceptable costs and risks of peritonitis in patients on
      peritoneal dialysis. New developments in catheter technology, improved
      connections, better understanding of patient selection and training programs,
      improved diagnostic and therapeutic methods in the management of peritonitis, and
      understanding of the infectious and immune processes are eagerly awaited
      developments.

PMID- 11570141
TI  - Surgical infections in patients with chronic renal failure.
AB  - Patients with chronic renal failure and uremia have impaired host defenses and
      wound healing that can lead to an increased risk of infection in addition to a
      frequent need for surgical procedures with synthetic grafts and catheters.
      Antibiotic therapy plus timely surgical intervention in removal of infected
      grafts and catheters is crucial for infection control and patient survival. Other
      surgical infections, such as wound problems, intraabdominal infections, fungal
      infections, diabetic foot ulcers, and necrotizing soft tissue infections must be
      attended to promptly.

PMID- 11570142
TI  - Infection control in hemodialysis units.
AB  - Infectious complications of hemodialysis include bacterial infections caused by
      contaminated water or equipment, other bacterial infections (including vascular
      access infections), and bloodborne viruses (primarily the hepatitis B and C
      viruses). Infections caused by contaminated water and equipment can be prevented
      by a well-designed water-treatment system, routine cleaning and disinfection of
      system components, and routine bacteriologic monitoring of dialysis water and
      dialysis fluid. Standard precautions with additional measures recommended
      specifically for dialysis centers will prevent transmission of bacteria and
      viruses from patient to patient. These precautions include routine use of gloves,
      handwashing, and cleaning and disinfection of the external surface of the
      dialysis machine and other environmental surfaces. In addition, preventing
      transmission of hepatitis B virus infection requires vaccination of susceptible
      patients and staff, avoiding dialyzer reuse, and use of a dedicated room,
      dialysis machine, and staff members when treating patients chronically infected
      with this virus.

PMID- 11570143
TI  - Immunologic defects and vaccination in patients with chronic renal failure.
AB  - Patients with chronic renal failure suffer from defective host defenses which are
      directly the result of the renal impairment, in addition to those dependent on
      the primary illness leading to the renal failure. The mechanisms underlying the
      defective responses in phagocytic cells, lymphocytes and antigen processing are
      likely due to either failure to adequately eliminate suppressive compounds by the
      defective kidneys or to improper metabolic processing of the factors by the
      damaged renal parynchema. That some of the defects are reversed by
      transplantation and not dialysis suggests that renal parenchymal metabolic
      activities may be involved, although it is also possible that functioning
      glomerular cells are capable of filtering substances that membranes are not
      currently capable of eliminating. The current strategy for dealing with the
      immunodeficiency appears to be totally based on developing means to circumvent
      the defective function. The other approach, correction of the impaired function,
      cannot be even considered until the mechanisms underlying the defective function
      of the cells involved in defenses are better delineated. It seems possible that
      one or a few compounds are pivotal in altering the function of all the affected
      cell lines, since, with only a small amount of effort, it is possible to relate
      the dysfunction to abnormal cell membrane functions in phagocytic cells,
      dendritic cells and lymphocytes. Until the biochemical basis of the dysfunction
      of all the cell types affected are better defined, such exercises cannot be
      translated into better management of patients with chronic renal failure. Proper
      function of host defenses requires that appropriate cells can properly respond to
      threats to host viability. For the cells of the immune system (phagocytes and
      lymphocytes) this means that their response to regulatory molecules be
      appropriate, that their mobility be normal, that their adherence to substrates be
      preserved, and that they can generate the appropriate response to the challenge.
      For neutrophils, for example, it is necessary that they recognize and mobilize
      appropriately to chemotactic stimuli, that they be able to adhere to and migrate
      through endothelial lining, that their phagocytic activity be sufficient, and
      that they can kill and degrade endocytosed particles and generate appropriate
      secretions. Similar lists of requirements for good function can be generated for
      any cell type in the immune defense system. Uremia, as well as currently
      available treatments for uremia, directly or indirectly alters the function of
      all phases of appropriate immune cell function. Defective host responses in
      uremia have been recognized for decades and there has been considerable effort in
      the past decade to better define the extent and mechanisms of impaired defenses.
      Despite the multitude of major defects in humoral, cellular, and inflammatory
      processes, uremic patients who are cared for today, although they remain at
      higher risk of serious infectious complications, can and do maintain a good
      quality of life, with most remaining free of major infections for years and
      decades.

PMID- 11570144
TI  - Human immunodeficiency virus infection and renal failure.
AB  - Renal manifestations are an important component of HIV disease. Renal disease
      significantly contributes to morbidity and mortality in patients with HIV. Great
      progress has been made in identifying specific glomerular lesions and its
      pathogenesis. Newer antiretroviral agents offer great promise in preventing renal
      disease and also in patients with established HIVAN. Survival of patients with
      HIV and ESRD (irrespective of cause) who are receiving RRT continues to improve
      over the years. Acute reversible renal failure, a preventable complication, is
      also declining in hospitalized HIV patients. More and more physicians, who in the
      past were reluctant to care for patients with HIV and renal failure because of
      grim prognosis, are now becoming familiar with the renal sequelae and are
      encouraged by recent favorable results. As knowledge about viruses is expanding,
      the proper use of newer highly effective antiretroviral and other agents in
      complicated patients should further improve both the survival and quality of life
      in patients with HIV infection and renal disease.

PMID- 11570145
TI  - Mycobacterial infections in patients with chronic renal disease.
AB  - In this article, the authors have provided a comprehensive review of TB and MOTT
      infections in patients on renal dialysis and receiving kidney transplants.
      Because most published series are small retrospective studies or case reports,
      there are several uncertainties still involved in the diagnosis and treatment of
      such patients. Unanswered questions include selection of optimal dosage and
      duration of therapeutic agents; the best tests for screening and diagnosis,
      especially in high prevalence areas; and the best management of MOTT infections
      because of unavailability of highly effective therapy.

PMID- 11570146
TI  - Hepatitis B and C and renal failure.
AB  - Hepatitis C is the most common cause of liver disease in the dialysis patient.
      The prevalence of chronic hepatitis C determined by anti-HCV testing in this
      population ranges from 6% to 38%. Using second generation EIA assays, the
      prevalence of anti-HCV among patients participating in the 1997 National
      Surveillance of Dialysis Associated Diseases in the United States was 9.3%.
      Polymerase chain reaction testing for HCV RNA has shown that the prevalence of
      HCV infection can be as high as 20% to 30% of dialysis patients. The causes and
      source of infection in patients with chronic renal failure on hemodialysis are
      multiple. Before the introduction of routine screening of blood donors for anti
      HCV, blood transfusions were an important risk factor for acquisition of
      hepatitis C. Other potential sources of infection include exposure to
      contaminated equipment and nosocomial routes such as patient-to-patient exposure.
      The risk of infection appears to correlate with the duration of hemodialysis and
      the number of transfusions. Interestingly, dialysate and buffers have been shown
      to be virus free even when used in hepatitis C infected patients. The natural
      history of chronic hepatitis C infection in patients with renal failure is not
      well characterized. Although persistent elevations in ALT levels occur in 12% to
      50% of dialysis patients, the frequency of persistently normal ALT levels in HCV
      infected dialysis patients appears to be higher than in HCV-infected patients
      without renal failure. Overt liver disease and liver failure rarely occur. The
      degree of inflammation in liver biopsies of renal failure patients is usually
      mild. Thus, progressive liver disease may be less common in patients with
      advanced renal disease but further studies are required to assess the true impact
      of hepatitis C infection in this high risk population. The impact of hepatitis C
      infection on morbidity and mortality of patients with end-stage renal disease
      remains poorly defined. Initial studies have failed to show a significant
      increase in mortality among HCV-infected hemodialysis or renal transplant
      patients within the first 5 years following transplantation. In contrast, recent
      studies with extended follow-up of renal transplant recipients suggest that
      hepatitis C infection may affect patient and graft survival during the second
      decade. Further studies are required to identify the mechanisms of infection of
      patients with end-stage renal disease and to define better treatment strategies
      for these patients before and after kidney transplantation.

PMID- 11570147
TI  - Infections in recipients of kidney transplants.
AB  - A review of infections in kidney transplant recipients is presented in this
      article, beginning with a discussion of the pretransplant infectious diseases
      evaluation and an overview of the timing of infectious posttransplant, and then
      focusing on individual types of infection.

PMID- 11570148
TI  - Saving the diabetic foot with special reference to the patient with chronic renal
      failure.
AB  - The chronic renal failure patient with diabetes has a lower limb amputation rate
      10 times greater than the diabetic population at large. In studies of causal
      pathways leading to non-traumatic related lower extremity amputation, foot ulcers
      preceded approximately 84% of the amputations. Even though foot ulcers are more
      likely to develop in patients with diabetic nephropathy, they are no less likely
      to heal than are those in diabetic patients with normal renal function.
      Consequently, attempts to save the diabetic foot even in this high-risk
      population are justified. The pathogenesis of foot ulceration in the chronic
      renal failure patient with diabetes is primarily due to peripheral neuropathy.
      Loss of protective sensation due to sensory neuropathy combined with motor and
      autonomic neuropathy and macrovascular compromise result in increased risk for
      foot complications. Evaluation of the foot includes a selective history and a
      focused examination of skin integrity, presence of sensory neuropathy or vascular
      insufficiency, and biomechanical and footwear inspection. Effective treatment of
      diabetic foot complications include appropriate antibiotics (when indicated),
      meticulous wound care, off-loading, vascular surgery (when indicated), and
      selective/elective or prophylactic nonvascular surgery. Failure to heal an ulcer
      can often be traced to common pitfalls, which include: A "cavalier" attitude.
      W.N.L. exam (We Never Looked). Inadequate off-loading. Failure to establish depth
      of ulcer and miss "probe to bone." Non-healing means unrelieved pressure and/or
      no blood. Failure to correct edema. The multidisciplinary diabetic foot clinic
      model provides an ideal setting for early intervention, treatment, and assistance
      with preventive strategies.

PMID- 11570149
TI  - Use of antibacterial agents in renal failure.
AB  - This article reviews the pharmacokinetics of antibacterial agents in patients
      with normal and decreased renal function. The concepts of volume and
      distribution, rate of elimination, loading and maintenance doses, and therapeutic
      drug monitoring are delineated. Special reference is made to the intermittent
      dosing of cefazolin with hemodialysis. Newer, as well as traditional methods of
      extracorporeal circulation and the resultant changes in antibacterial agent
      pharmacodynamics are discussed.

PMID- 11570150
TI  - Clinical use of pulmonary mechanics and waveform graphics.
AB  - Decades of research have led to the understanding of neonatal pulmonary
      physiology and have influenced the clinical care that neonatologists provide to
      the sick newborn. Advances in microprocessor technology have allowed for clinical
      access of the research-based measurements of neonatal pulmonary functions. These
      evaluations are not only the integrated evaluation of the three primary vectors
      of respiration (driving pressure, air flow, and volume measured over time) but
      also values calculated by known physiologic equations. Clinical use of these data
      may not only be relevant and helpful in the bedside management, but also provides
      a uniquely objective and research-oriented data collection for individual
      newborns.

PMID- 11570151
TI  - Volutrauma. What is it, and how do we avoid it?
AB  - Lung injury can be initiated at birth with the delivery room resuscitation.
      Adequate tidal volume must be achieved gradually and adjusted with each
      subsequent breath to achieve adequate, but not excessive, tidal volume delivery.
      Time constants vary greatly within the lung because some alveoli are collapsed,
      and some are inflated. Excessive pressure or volume may lead to high stretch
      injury when already open alveoli are overdistended. Sufficient alveoli must be
      recruited to establish the optimal functional residual capacity. This establishes
      an inflation history of the lung that tends to resist alveolar collapse at the
      end of expiration, provided that adequate mean airway pressure is provided
      throughout the ventilatory cycle. The best volume of inflation is achieved at the
      lowest pressure cost. Maintaining alveolar recruitment with the use of exogenous
      surfactant and positive end-expiratory pressure avoids alveolar collapse and
      injury with succeeding distending breaths. Although there have been significant
      advances in neonatal respiratory care, further improvement in outcomes may be
      expected by successfully avoiding ventilator-induced lung injury.

PMID- 11570152
TI  - Hypocapnia and hypercapnia in respiratory management of newborn infants.
AB  - Recent experimental and clinical data demonstrate that both hypocapnia and
      hypercapnia during the neonatal period may result in beneficial or adverse
      consequences. Multiple retrospective studies report a strong association between
      PaCO2 levels less than 25 to 30 mm Hg and an increased incidence of cystic PVL
      and CP in preterm infants. Prolonged exposure to PaCO2 values less than 25 to 30
      mm Hg is also associated with hearing loss in term and near-term infants. A low
      tidal volume strategy combined with permissive hypercapnia is potentially a
      strategy that could prevent lung injury. Clearly, more randomized, controlled
      trials are needed before this latter strategy or that of permissive hypercapnia
      can be recommended routinely for preterm, near-term, or term gestation infants
      with respiratory disorders.

PMID- 11570153
TI  - Update on patient-triggered ventilation.
AB  - Physiologic studies have demonstrated short-term benefits of triggered
      ventilation over conventional ventilation. The results of the randomized trials
      are disappointing. Meta-analysis has highlighted that the only significant
      difference in outcomes on PTV compared with conventional ventilation is a shorter
      duration of weaning. A few of the trials included infants with meconium
      aspiration syndrome and congenital pneumonia, but most infants randomized had
      RDS. In addition, a high proportion of the infants included in the meta-analysis
      were from two trials in which the SLE 2000 and airway pressure triggering system
      were mainly used. We cannot confidently conclude that in a population of infants
      with another respiratory disorder or even in those with RDS supported by an
      alternative triggering system, a different result might have been achieved. In
      addition, the benefits of PTV demonstrated in physiologic studies are largely
      related to achieving synchronized ventilation. In none of the randomized trials
      was any attempt made to determine if the infants were breathing synchronously
      with their ventilators. Before dismissing PTV for use in the management of
      infants with acute respiratory distress, an appropriately designed trial needs to
      take place. Essential, before any such trial, is identification of optimum method
      of PTV delivery, which may be disease specific.

PMID- 11570154
TI  - Volume-controlled ventilation. Variations on a theme.
AB  - Development of sophisticated transducers and microprocessor-based ventilators now
      enables the performance of volume-controlled ventilation of newborn infants.
      Volume-controlled modes include standard intermittent or synchronized
      intermittent mandatory ventilation; assist-control ventilation; and hybrid modes,
      such as pressure-support ventilation, pressure-regulated volume-control
      ventilation, volume-assured pressure support, and volume guarantee. This article
      describes the concepts and clinical applications of these ventilatory modes.

PMID- 11570155
TI  - Proportional assist ventilation in infants.
AB  - Proportional assist ventilation and respiratory mechanical unloading is a new
      mode of respiratory assistance that produces similar gas exchange with lower
      airway pressures than conventional ventilation in infants. This is achieved by
      tailoring the ventilator pressure contour to the specific derangements in lung
      mechanics and by a near perfect synchronization with the infant's own inspiratory
      effort. In contrast to conventional ventilation, PAV only amplifies the effect on
      ventilation of the spontaneous respiratory effort and relies on the subject's
      respiratory control. Whether PAV will reduce the incidence of acute complications
      and chronic pulmonary sequelae in infants needs to be evaluated in randomized
      controlled trials.

PMID- 11570156
TI  - Neonatal high-frequency ventilation. Past, present, and future.
AB  - High-frequency ventilation has become established as an effective treatment
      modality in a variety of clinical situations. The laboratory and clinical
      investigations of these techniques have contributed tremendously to our
      understanding of the pathophysiology of respiratory failure and the important
      concept of maintaining adequate lung volume. Clinicians have come to appreciate
      better the factors involved in lung injury and the potential for damage to
      distant organs. The place of HFV in the therapeutic armamentarium will
      undoubtedly continue to evolve in the years to come. Of particular interest is
      the advent of advanced modes of fully synchronized and volume-targeted
      conventional mechanical ventilatory modes, along with the trend to use smaller
      tidal volumes and higher levels of PEEP with conventional ventilation. With these
      developments there seems to be a certain convergence of HFV and tidal ventilation
      that is the logical result of our improved understanding of respiratory
      pathophysiology. The available controlled trials of HFV versus tidal ventilation
      do not clearly differentiate whether improved outcomes are the result of HFV per
      se, or a reflection of the effects of optimizing lung volume, a benefit that may
      not be unique to HFV.

PMID- 11570157
TI  - Persistent pulmonary hypertension of the newborn. Rational therapy based on
      pathophysiology.
AB  - Persistent pulmonary hypertension of the newborn is a common disorder among near
      term gestation newborns. Persistent pulmonary hypertension of the newborn is
      characterized by hypoxemia that is frequently refractory to conventional
      management. This article describes the pathophysiologic basis of the disorder and
      the current therapy that is based on this knowledge.

PMID- 11570158
TI  - Extracorporeal membrane oxygenation 2001. The odyssey continues.
AB  - Extracorporeal membrane oxygenation was established as a standard of care by
      demonstrating its ability to save lives in moribund infants. The designs of early
      studies provided no living cohorts of similarly ill patients by which to measure
      accurately other (and perhaps to many more important) outcomes of interest: long
      term neurodevelopmental outcomes or cost. Prospective cohort studies of
      neurodevelopmental outcomes post-ECMO demonstrate: (1) because ECMO, as used,
      saves lives, there will be an increase in the absolute number of handicapped
      children surviving; (2) there is little evidence that ECMO creates a relative
      increase in the percent of handicapped children surviving severe respiratory
      failure. The high direct costs of an ECMO program are measured and well
      publicized. When such costs are compared with similar therapies in other fields
      (in such terms as cost per survivor), the cost of ECMO does not seem to be an
      outlier. Trials of newer therapies, such as iNO, show the capacity to decrease
      the use of ECMO but have failed to demonstrate either cost-effectiveness or
      better long-term outcomes. It has not been shown that either society or
      individual patients have benefited from the decreased need for ECMO.

PMID- 11570159
TI  - Biology of surfactant.
AB  - Surfactant is a metabolically active assembly of phospholipids and surfactant
      specific proteins that is essential for normal lung mechanics. The surfactant
      proteins SP-A and SP-D also have important innate host defense functions.
      Surfactant metabolism in the developing lung differs from the adult lung by
      having slower kinetics of secretion with a longer half-life and more efficient
      recycling. Ventilation styles that injure the lung also result in altered
      surfactant function.

PMID- 11570160
TI  - Current surfactant use in premature infants.
AB  - Exogenous surfactant therapy has been a significant advance in the management of
      preterm infants with RDS. It has become established as a standard part of the
      management of such infants. Both natural and synthetic surfactants lead to
      clinical improvement and decreased mortality, with natural surfactants having
      additional advantages over currently available synthetic surfactants. The use of
      prophylactic surfactant administered after initial stabilization at birth to
      infants at risk for RDS has benefits compared with rescue surfactant given to
      treat infants with established RDS. In infants who do not receive prophylaxis,
      earlier treatment (before 2 hours) has benefits over later treatment. The use of
      multiple doses of surfactant is a superior strategy to the use of a single dose,
      whereas the use of a higher threshold for retreatment seems to be as effective as
      a low threshold. Adverse effects of surfactant therapy are infrequent and usually
      not serious. Long-term follow-up of infants treated with surfactant in the
      neonatal period is reassuring. In the future we are likely to see the development
      of new types of surfactants. Further research is required to determine the
      optimal use of surfactant in conjunction with other respiratory interventions.

PMID- 11570161
TI  - Expanded uses of surfactant therapy.
AB  - There are few therapies for which the cumulative evidence of benefit is as much
      as that for surfactant therapy for RDS in premature infants. Exogenous surfactant
      therapy does seem to be beneficial for a number of non-RDS disorders. Although
      there are some trials supporting its use in MAS and ALI-ARDS, there are only a
      few small prospective, randomized, controlled trials supporting surfactant use in
      non-RDS disorders. Use of surfactant therapy for any disorder other than RDS must
      be considered "off the shelf" and experimental. Much work remains to be done to
      address the role of surfactant therapy in the myriad disorders discussed. Of
      import for each of the disorders is addressing the optimum type of surfactant to
      use, and the appropriate dose, method of delivery, and duration of treatment
      regimens.

PMID- 11570162
TI  - Liver fibrosis in HIV/hepatitis C coinfection: HIV protease inhibitors may be
      protective.

PMID- 11570164
TI  - Homocysteine, HIV, and heart disease.
AB  - Too much homocysteine in the blood is associated with an increased risk of heart
      and circulatory diseases. Blood tests can detect the problem, and it can often be
      treated with nutrition and suplements. Here is some background on this potential
      approach to reducing cardiovascular risk.

PMID- 11570163
TI  - Tenofovir: FDA hearing October 3, public comment deadlines September 26.

PMID- 11570166
TI  - Action alert: global AIDS funding.

PMID- 11570165
TI  - AIDS treatment activists form new coalition.
AB  - A new treatment activist coalition, formed in mid August, will develop national
      strategies plan mentoring of new activists, and help persons with HIV and
      activists find consensus and work together on issues involving treatment research
      and access to care.

PMID- 11570167
TI  - Proceedings of the 4th International Symposium on the Epidemiology and Control of
      Salmonella and other Food Borne Pathogens in Pork. September 2001, Leipzig,
      Germany.

PMID- 11570168
TI  - A new Salmonella surveillance and control programme in Danish pig herds and
      slaughterhouses.
AB  - The Danish Salmonella Surveillance and Control Programme for pigs operates at all
      stages of the production chain and has been applied nationally since 1995. Due to
      the program the level of Salmonella in Danish pork has declined from 3.5% in 1993
      to 0.7% in the year 2000. Simultaneously, the number of human cases with
      salmonellosis due to pork has declined from approximately 1,144 in 1993 to 166 in
      2000. In year 2001, the programme has been improved at a number of stages. A new
      classification scheme for the serological surveillance of finisher herds has been
      developed. The individual test cut-off in the mix-ELISA has been reduced to 20
      OD%. Only herds producing more than 200 finishers/year are sampled. Based on the
      serological result from the last 3 months a new weighted salmonella index is
      calculated: The Danish Bacon and Meat Council has agreed on a new stricter
      penalty system. Level 2 and 3 herds get a penalty of 2% and 4% of the value per
      slaughter carcass, respectively. A new method of Salmonella testing on carcasses
      has been introduced; 5 carcasses per slaughter day are swabbed at 3 defined areas
      at 100 cm2 for each sample. This method is more sensitive than the one used
      previously. Herds infected with multiresistant Salmonella Typhimurium DT104 have
      to follow special restrictions. These include a requirement for a herd
      intervention plan, restriction on livestock trade, and a requirement for special
      slurry handling. Carcasses from DT 104 herds must be heat-treated or
      decontaminated with hot water.

PMID- 11570169
TI  - The Hazard Analysis and Critical Control Points (HACCP) generic model for the
      production of Thai fermented pork sausage (Nham).
AB  - Nham is a traditional Thai fermented pork sausage. The major ingredients of Nham
      are ground pork meat and shredded pork rind. Nham has been reported to be
      contaminated with Salmonella spp., Staphylococcus aureus, and Listeria
      monocytogenes. Therefore, it is a potential cause of foodborne diseases for
      consumers. A Hazard Analysis and Critical Control Points (HACCP) generic model
      has been developed for the Nham process. Nham processing plants were observed and
      a generic flow diagram of Nham processes was constructed. Hazard analysis was
      then conducted. Other than microbial hazards, the pathogens previously found in
      Nham, sodium nitrite and metal were identified as chemical and physical hazards
      in this product, respectively. Four steps in the Nham process have been
      identified as critical control points. These steps are the weighing of the
      nitrite compound, stuffing, fermentation, and labeling. The chemical hazard of
      nitrite must be controlled during the weighing step. The critical limit of
      nitrite levels in the Nham mixture has been set at 100-200 ppm. This level is
      high enough to control Clostridium botulinum but does not cause chemical hazards
      to the consumer. The physical hazard from metal clips could be prevented by
      visual inspection of every Nham product during stuffing. The microbiological
      hazard in Nham could be reduced in the fermentation process. The critical limit
      of the pH of Nham was set at lower than 4.6. Since this product is not cooked
      during processing, finally, educating the consumer, by providing information on
      the label such as "safe if cooked before consumption", could be an alternative
      way to prevent the microbiological hazards of this product.

PMID- 11570170
TI  - Eradication of Salmonella Yoruba in an integrated pig herd.
AB  - An integrated SPF herd with 320 sows was found infected with Salmonella Yoruba
      during an annual control among sows, aiming to verify freedom from Salmonella
      infections. It is believed that the infection was introduced to the herd by
      purchase of feed. The herd performed an age segregated rearing system. Sows and
      piglets were reared at a central farm, while growers (25-100 kg body weight) were
      reared at sub-estates. The growers were free from the infection, and as a
      consequence a specially designed eradication program was designed. Farrowing and
      weaning were defined as periods of risk for sows and piglets, respectively.
      Consequently sows were isolated and individually tested for presence of
      Salmonella one week before and one week after farrowing. The offspring were
      tested one week post weaning. To verify freedom from disease among piglets they
      were also tested another time before transfer to the uninfected sub-estates.
      Piglets with undefined status regarding Salmonella were denoted animals at risk
      and not transferred to the sub-estates. Instead they were transferred to a third
      estate, rented to house pigs at risk. The program was successful. It allowed full
      production during performance, and the herd was declared free from S. Yoruba
      seven and a half months after the initial diagnosis.

PMID- 11570171
TI  - Risk factors associated with Salmonella enterica prevalence in three-site swine
      production systems in North Carolina, USA.
AB  - The goal of this study was to identify risk factors associated with increased
      fecal shedding of Salmonella enterica (SE) in groups of market swine reared in
      large three-site production units. We conducted an intensive, long-term
      investigation of potential management and environmental risk factors operating
      during the growing phase of pig production. Data regarding finisher site
      characteristics, biosecurity protocols, group growth performance, medication
      usage, and environmental temperature were collected. Results indicate that SE
      infection is common. Risk factors were identified at both the finisher site and
      group level. Biosecurity and hygiene practices (absence of a toilet, more than 2
      people present at a finisher site daily, and other domestic species at the site),
      environmental temperature (winter and spring seasons, increased temperature
      variability, and below median high temperature the day of sampling), and
      production performance (above median feed conversion) were associated with
      elevated SE prevalence. In addition, an association between the floor space
      allowances per pig at the time of sampling (a measure of the number of pigs sold
      prior to sampling) was identified, with greater space allowance associated with
      decreased prevalence. The results of this study identify potential management
      practices for evaluation for SE control and suggest caution in interpretation of
      fecal culture results when sampling from different marketing groups in swine
      production systems.

PMID- 11570172
TI  - Evaluation of cross-protection afforded by a Salmonella Choleraesuis vaccine
      against Salmonella infections in pigs under field conditions.
AB  - This field study investigated the efficacy of a Salmonella Choleraesuis live
      vaccine (Argus SC) to reduce the number of infections with Salmonella. Twelve
      groups of about 380 pigs each were randomly allocated to either vaccination (V)
      or no vaccination (C). The vaccine was applied orally at 3 and 16 weeks. Forty
      pigs per group were blood sampled at 3, 10, 16, and 24 weeks to detect possible
      antibodies against Salmonella. The prevalence of Salmonella in the lymph nodes
      was the major variable. In the V groups, only 0.6% of the lymph nodes were
      positive, whereas 7.2% were positive in the C groups (p < 0.001). The percentage
      of seropositive pigs at 24 weeks (cut-off OD > 10) was 26% and 9% in the V and C
      groups, respectively (p < 0.001). The present study documented that vaccination
      with a live modified S. Choleraesuis vaccine is a useful tool to lower the
      prevalence of Salmonella in swine herds.

PMID- 11570173
TI  - Investigation of the efficacy of a genetically-stabile live Salmonella
      typhimurium vaccine for use in swine.
AB  - Hybrid swine (Landrace x Pietrain) aged 3-4 weeks were immunized twice at an
      interval of 3 weeks solely by the oral route and by the oral/parenteral route to
      evaluate the efficacy of a live S. Typhimurium vaccine. In each experiment a
      control group was run without vaccination. The animals were challenged at the age
      of 8-10 weeks by oral test infection with a labelled S. Typhimurium DT 104
      strain. An ELISA was used to establish the presence of antibodies to S.
      Typhimurium in serum samples, coupled with clinical investigation. The presence
      of the challenge strain in the ileal and caecal mucosa and in the ileocolic lymph
      nodes was investigated quantitatively using the Koch plating method to determine
      the degree of colonization of those organs at the time of slaughter. The clinical
      course of disease was used to assess the success of vaccination. However, it was
      not possible to trigger, in a reproducible manner, clinical signs of disease in
      unvaccinated animals through infection. The vaccinated animals had a
      significantly lower (p < 0.05) colonization of the ileal and caecal mucosa than
      the unvaccinated animals. This was also seen to a lesser degree for the ileocolic
      lymph nodes.

PMID- 11570174
TI  - Trends and seasonal variations in the occurrence of Salmonella in pigs, pork and
      humans in Denmark, 1995-2000.
AB  - A mandatory programme monitoring the occurrence of Salmonella in pork at
      slaughterhouses and a serological monitoring of slaughter-pig herds has been
      implemented in Denmark since 1993 and 1995, respectively. All results are stored
      in a central database. From this, aggregated weekly results of serological and
      bacteriological samples collected in the period between January 1995 and July
      2000 were extracted. In addition, the reported weekly incidence of human
      infections with S. Typhimurium covering the same time period was obtained. The
      times series were analysed for trends and cyclic variations by seasonal
      decomposition. The association between the incidence in humans and the prevalence
      of Salmonella in pigs and pork, and prevailing weather conditions, were analysed
      by using a general linear (glm) and a general additive model (gam). Explanatory
      variables were lagged to account for time elapsed between sampling, consumption,
      incubation period and case registration. The results of the seasonal
      decomposition showed an overall declining trend in all three time series. All
      time series exhibited a double peaked annual cycle. The seasonal variation of the
      prevalence in pork and the human incidence had a very similar course. The
      variables that were both biologically meaningful and statistically significant in
      both regression models were the prevalence in pork sampled 4 to 5 weeks before
      case registration, the seroprevalence, measured as the average prevalence of week
      15 to 35 before case registration, and the air temperature lagged at 2 and 3
      weeks. Limitations on inferences from overall surveillance data are discussed.

PMID- 11570175
TI  - Bacteriological and serological examination and risk factor analysis of
      Salmonella occurrence in sow herds, including risk factors for high Salmonella
      seroprevalence in receiver finishing herds.
AB  - A strong association between the seroprevalence in sows and the occurrence of
      Salmonella Typhimurium among weaners has been shown. As shown several times for
      finisher herds, the risk-factors, ready mixed pelleted feed and health status
      also apply to sow herds. Risk factors on the sow level, for high seroprevalence
      in finishers have been quantified. It has been shown, that isolating Salmonella
      in weaners is a risk factor for high seroprevalence in finishers. Feed factors;
      ready-mixed pelleted feed for both sows and finishers, dry feed for sows, have
      been shown to have a significant effect on high seroprevalence, monitored by meat
      juice samples at slaughter. The etiological fraction of ready-mixed pelleted feed
      for sows and for finishers is of the same magnitude, indicating that intervention
      on the sow level could prove to contribute considerably to the effect of
      intervention programs.

PMID- 11570176
TI  - Impact of commercial pre-harvest processes on the prevalence of Salmonella
      enterica in cull sows.
AB  - This study examined the impact of transport and lairage on Salmonella enterica
      prevalence in cull sows held under commercial conditions. Five sampling periods
      over 10 weeks yielded 181 selected culls. Fecal sample positives at the farm and
      collection point were 2% and 3%, respectively. After transport and lairage 41% of
      cull sows yielded S. enterica in one or more sampled tissues. A significant
      increase in cecal isolations was observed. The two S. enterica serotypes found at
      the production site and collection point were found at the abattoir, as were 13
      other serotypes. Transport and lairage practices may contribute to an increased
      S. enterica contamination immediately prior to slaughter.

PMID- 11570177
TI  - Epidemiological investigations into the sources of Salmonella contamination of
      pork.
AB  - This study was conducted to elucidate which phases of the pork production chain
      contribute to the Salmonella contamination on pork after slaughter. During 7
      sampling days, samples were collected of randomly selected slaughter pigs and of
      pigs from selected Salmonella-infected and Salmonella-free herds, trucks,
      lairages, and slaughterlines, in two slaughterhouses. Salmonella genotypes,
      present on pork after slaughter, were compared with Salmonella types, present on
      the farm, in the truck, in the lairage, on slaughter equipment, and in pigs from
      other herds. Results showed that the slaughterline was the most important source
      of Salmonella contamination of carcasses. The farm was the most important source
      of contamination of livers, tongues, rectal samples and mesenterial lymphnodes,
      for pigs originating from sero-positive herds. The lairage was the most important
      contamination source for pigs originating from sero-negative herds, for all
      samples, except carcasses. It is recommended to avoid each direct or indirect
      contact between different herds along the whole pork production chain, especially
      between Salmonella-infected and Salmonella-free herds.

PMID- 11570178
TI  - Prevalence of Salmonella serotypes on pig carcasses from high- and low-risk herds
      slaughtered in three abattoirs.
AB  - The aim of this study was to compare the prevalence of Salmonella serotypes at
      two different sites on pig carcasses from herds classified as high-risk or low
      risk and to elucidate the relationship between carcass contamination levels and
      serological status. Caecal samples and carcass surface swabs were cultured for
      Salmonella from a total of 210 pigs from low risk herds (< 19% of pigs in herd
      Salmonella seropositive) and 209 pigs from high risk herds (> 32% of pigs in herd
      Salmonella seropositive) in three abattoirs. Meat juice samples were collected
      for analysis by ELISA. The prevalence of Salmonella in the caecal contents of
      "low-risk" pigs was 10%, which was significantly lower than the 19% prevalence in
      "high-risk" pigs (p < 0.01). The corresponding figures for skin samples collected
      immediately post-evisceration were 2% and 12%. The predominant Salmonella
      serotype in the caecal contents of both the low-risk and high-risk pigs was
      Salmonella Typhimurium. Salmonella Kentucky and Salmonella Derby were the most
      frequent isolates from the carcass surface swabs of low- and high-risk pigs
      respectively. There was a positive association between seropositivity of pigs
      from high-risk herds and caecal carriage (p < 0.05). Results showed that herd
      categorisation based on serological results was useful in predicting Salmonella
      isolation rates from caecal samples and surface swabs of slaughtered pigs.

PMID- 11570179
TI  - Effect of separate transport, lairage, and slaughter on occurrence of Salmonella
      typhimurium on slaughter carcasses.
AB  - The study aimed to reduce cross-contamination between finishers from Salmonella
      positive and Salmonella-negative herds during transport, lairage, and slaughter,
      thereby reducing the prevalence of Salmonella Typhimurium on slaughter carcasses.
      In Phase 1 of the study, pigs from Salmonella-negative herds were kept in lairage
      for 2-4 hours either in clean pens (intervention group) or pens contaminated with
      Salmonella-infected faeces (control group). All pigs were slaughtered on the same
      slaughterline, and carcass swabs 24 hours after slaughter revealed a low degree
      of cross-contamination in the pens: there was no difference in Salmonella
      positive carcasses between intervention (1.7%) and control groups (0.8%). In
      Phase 2, control pigs from Salmonella-negative herds were mixed with pigs from
      Salmonella-positive herds during lairage for 2-4 hours, while the intervention
      group still consisted of pigs from Salmonella-negative herds. All pigs were
      slaughtered on the same line: first intervention, then control. Carcass swabs
      taken 24 hours after slaughter failed to show a reduction in Salmonella-positive
      carcasses in the intervention group (4.5%) compared with the originally
      Salmonella-negative pigs in the control group (3.6%). In pigs from Salmonella
      positive herds the occurrence of Salmonella was substantially higher at 10.4%.
      When the results were corrected for 6 carcass samples found positive with S.
      Heidelberg on the same day, which was attributed to a transient hygiene failure,
      only 2.2% of the carcasses in the intervention group were Salmonella-positive. We
      conclude that even though cross-contamination occurs in the abattoir pens, its
      importance on the slaughter line may be greater. However, the final results of
      this study should be awaited to conclude whether separate slaughter of pigs from
      Salmonella-positive and Salmonella-negative herds should be recommended.

PMID- 11570180
TI  - Assessment of the human risk associated with use of pork with possible presence
      of Salmonella typhimurium DT104 for dry-cured sausages.
AB  - We examined whether pork with suspected content of Salmonella Typhimurium DT104
      (DT104) could be used for production of dry-cured sausages without jeopardizing
      consumer safety. The results of the risk assessment showed, that if Salmonella is
      present in raw pork, it is usually in low numbers. Additionally, during
      processing, an eventual presence of Salmonella will be reduced with at least two
      log units. The simulations showed that only 1-2 DT104 would be present in dry
      cured sausages made by Danish pork, and this extremely seldom. Likewise, up to 4
      DT104 would be present in dry-cured sausages made by foreign pork. It is not
      clear whether these low numbers of DT104 are capable of producing disease at all.
      However, if higher numbers are present, disease might occur. Therefore, we set up
      a monitoring and managing program, including a list with demands to processing in
      order to achieve minimum two-log reduction of any DT104 bacteria. The suggested
      scheme implies a far better and more systematic monitoring than the current
      system, ensuring the consumer a higher degree of food safety.

PMID- 11570181
TI  - Long-term survival and infectivity of Salmonella choleraesuis.
AB  - It is believed that Salmonella Choleraesuis, the host-adapted serotype of swine,
      does not survive well outside the host. We examined the survival capability as
      well as the presence of latent DNA of S. Choleraesuis in swine feces. Pigs were
      infected with S. Choleraesuis and feces was collected and pooled on days 2, 4, 7,
      and 10 post inoculation (PI). Feces was stored in a wet and a dry form and
      survival was measured over 13 months. Salmonella Choleraesuis was recovered from
      wet feces through 3 months of storage. In a desiccated (dry) form, S.
      Choleraesuis was recovered from at least 13 months. Direct PCR analysis did not
      detect S. Choleraesuis subsequent to the final culture recovery for any stored
      sample. We also examined the infectivity of S. Choleraesuis resident in dry
      feces. Six or 13 week old pigs were inoculated with dry feces that had been
      stored either 2 months or 4 months, respectively. Pigs were inoculated either
      intranasally or by mixing dry feces with the swine ration. Although clinical
      signs were mild, S. Choleraesuis was widely disseminated among the tissues of all
      the pigs inoculated. This study demonstrates that S. Choleraesuis remains viable
      and infective in the environment. Therefore, contaminated fecal matter can serve
      as a reservoir for S. Choleraesuis as well as other Salmonella spp. Control
      measures must consider this environmental reservoir as a source of new
      infections.

PMID- 11570182
TI  - Transport stress--consequences for bacterial translocation, endogenous
      contamination and bactericidal activity of serum of slaughter pigs.
AB  - On transport and at the abattoir animals are confronted with a lot of stressors,
      such as sound/noise, crowding/mixing, pollutants and infectious agents that act
      on the organism. After transport stress an endogenous contamination is often seen
      in slaughter carcasses and presents a hazard for the consumer. These events are
      often correlated with a rise in endotoxin level (Misawa et al., 1995; Morales et
      al., 1992) and a modified immune response. Previous own investigations confirm
      this hypothesis (Zucker and Kruger, 1998, Seidler et al., 2000). The attempt was
      made to investigate the impact of selected stressors (short term transport (1 h),
      long term transport (7-8 hrs), high temperature, high humidity and intense
      handling/moving) on bacterial translocation, endogenous contamination, endotoxin
      levels and bactericidal activity of body fluids.

PMID- 11570183
TI  - A bioreactor system to study survival of Salmonella Typhimurium in pig gut
      content.
AB  - The batch culture system included six bioreactors. Three bioreactors containing
      stomach slurry were maintained at pH 4.5 and 6 respectively. Bioreactors
      containing small intestine slurry were maintained at pH 5.6 and 7 respectively.
      The bioreactors were inoculated with 10 ml of viable Salmonella. The bioreactors
      were maintained for 6 hours. Samples of 10 ml were taken at 0 time and at 1, 2, 4
      and 6 hours. The samples were analysed for the presence of Salmonella and SCFA.
      In the stomach samples Salmonella numbers increased at pH 6 but fell at pH 4. In
      the small intestine sample Salmonella numbers increased at pH 6 and 7. In terms
      of SCFA production, in the stomach, with samples at pH 6 there was little change
      in the amounts of lactate, succinate and formate to that detected at 0 time,
      however levels of acetate did increase slightly. In the small intestine samples
      levels of succinate and formate increased slightly up to 4 hours, levels of
      acetate increased significantly from 0 to 6 hours. In terms of the specific
      growth rates of the individual strains, both strains grew at pH 6 in the stomach
      content and to a greater extent in the small intestinal content. A bactericidal
      effect was observed at pH 4 in the stomach content while neither killing nor
      growth occurred at pH 5 either in the stomach or the small intestine content.
      Both strains grew well in the small intestine content at pH 7, showing generation
      times of up to 24 min.

PMID- 11570184
TI  - Experimental rapid infection in market swine following exposure to a Salmonella
      contaminated environment.
AB  - The objective of these experiments was to evaluate the possibility of swine
      becoming infected with Salmonella Typhimurium after a short time interval in a
      contaminated environment. Two experiments were conducted. Experiment 1 consisted
      of five trials with eight market weight swine. Pigs were necropsied at 2 (n =
      10), 3 (n = 10) and 6 (n = 5) hours after continuous exposure to an environment
      contaminated with feces shed by swine intranasally inoculated with nalidixic acid
      resistant Salmonella Typhimurium (chi 4232). In Experiment 2, pigs were
      necropsied after 30 minutes (n = 6), 60 minutes (n = 6), 2 hours (n = 6), and 6
      hours (n = 3). In addition, control animals with no exposure were also necropsied
      in both experiments. At necropsy, the superficial inguinal, ileocecal, and
      mandibular lymph nodes, as well as cecal contents, distal ileum portion, and
      feces were evaluated. All samples were cultured for the presence of the nalidixic
      acid-resistant Salmonella. Feces deposited on the floor by intranasally
      inoculated swine were mixed with water to form slurry with a resulting load of
      10(3)-10(5) Salmonella Typhimurium CFU per gram. In Experiment 1, 80% percent of
      animals with a 2-hour, 60% of animals with a 3-hour, and 100% of animals with a 6
      hour exposure to this slurry had at least one sample test positive for the marked
      Salmonella Typhimurium strain. In Experiment 2, 50% of the 30 minute, 50% of the
      60 minute, and 33% of the 2-hour exposed pigs had at least one sample test
      positive. These experiments show that market swine can become infected during
      routine resting or holding periods when exposed to relatively low levels (10(3)
      CFU) of Salmonella in the simulated pre-slaughter environment, and that exposure
      times as short as 30 minutes are sufficient to produce contaminated
      gastrointestinal tracts. They also demonstrate the high risk of holding pigs
      longer than six hours. Intervention at this step in the swine production process
      may have a significant impact on the safety of pork products.

PMID- 11570185
TI  - Influence of long-time transportation stress on re-activation of Salmonella
      typhimurium DT104 in experimentally infected pigs.
AB  - In this study a Salmonella Typhimurium infection model in swine was used in order
      to investigate the influence of pre-mortal stress induced by long time period
      transportation on the re-activation of Salmonella in experimentally infected
      pigs. Salmonella free pigs were exposed to a highly virulent strain of Salmonella
      Typhimurium DT104 by direct intragastrical administration. Clinical parameters
      were monitored and the shedding rate in faeces was qualitatively and
      quantitatively determined by standard bacteriological procedures for 21 days. The
      distribution of the challenge organism in 14 different internal organs of
      transported and nontransported animals was determined. All infected animals
      developed clinical signs of salmonellosis 12 to 24 hours post infection. About 88
      to 100% of the fecal samples were culture-positive up to post exposure day 6, and
      then varied from 71 to 92% until slaughter, respectively. At necropsy S.
      Typhimurium was recovered most frequently from caecum and ileocolic lymph nodes
      (83%), colon (79%), palatine tonsils (71%) and mandibular lymph nodes (62.5%). A
      negative impact of transportation stress on the shedding rate and the general
      condition of the animals was observed.

PMID- 11570186
TI  - First international ring trial of ELISAs for Salmonella-antibody detection in
      swine.
AB  - An international ring trial for Salmonella-ELISAs for swine serology was
      organized. Twelve laboratories participated and used "in-house" ELISAs or
      commercially available kits. In total 47 well-defined sera from various sources,
      including inoculation studies with Salmonella-strains from sero-groups B, C1, C2,
      D, and E1, were tested blindfold. The specificity of most ELISAs was
      satisfactory, but relatively large differences were found between the
      sensitivities of the tests. It is concluded that international reference samples
      should be made available to guarantee a minimum level of sensitivity.

PMID- 11570187
TI  - Feasibility of fluorescent detection of pathogens on pork carcasses.
AB  - The direct immunofluorescent detection of pathogens on pork skin is evaluated.
      Calibrate contamination of pork skin with Salmonella Typhimurium (ST) and
      Listeria monocytogenes (Lm) is developed in 2 h at 4 degrees C. Then a specific
      indirect immunofluorescent staining protocol is optimized in order to obtain
      specific and intensive signals able to be detected by electronic cameras
      (deported microscopy). Despite the individual staining of ST and Lm is possible
      on pork skin and is specific and bright, the deported microscopy failed to detect
      these particles. After respectively 3 and 6 h, we obtain micro-colonies of ST and
      Lm. Due to the limited power of the video camera used, only the microscope
      permits the detection on the skin. However, our work gives standard conditions to
      mime the pathogens contamination and staining directly on a biological matrix
      such as pork skin. This work is a first step in the development of direct and
      rapid detection of pathogens on biological matrix.

PMID- 11570188
TI  - Identification of patterns of transmission of Salmonella within swine production
      systems using pulsed field gel electrophoresis (PFGE) and repetitive sequence
      polymerase chain reaction (REP-PCR): a quantitative analysis.
AB  - Pulsed field gel electrophoresis (PFGE) using 3 enzymes (Spe I, Xba I, Avr II)
      and repetitive sequence polymerase chain reaction (REP-PCR) with 3 primers (BOX,
      ERIC, REP) were compared with respect to their validity as a method for
      identifying transmission of Salmonella on swine farms. Sixty-eight isolates of
      Salmonella were obtained from feces of swine, cats, mice, and birds, insect body
      parts, water and floor samples, and boot scrapings collected on 9 swine farms in
      Illinois USA. Genetic distances between isolates were calculated using the Dice
      matching coefficient. Cluster analysis of distance matrices was conducted using
      the UPG-MA algorithm. There was no significant difference between PFGE and REP
      PCR in the genetic diversity detected; however, REP-PCR differentiated between 14
      pairs of isolates which PFGE identified as identical. There were no significant
      differences between PFGE and REP-PCR in identifying all or most close genetic
      links as isolates from the same farm, the same building, and from the same
      sampling visit, suggesting ecological validity for both methods. Thus, REP-PCR
      should be considered as an acceptable and perhaps preferable alternative to PFGE
      as a genotyping method for studies of Salmonella transmission.

PMID- 11570189
TI  - Improvement of an invA-based PCR for the specific detection of Salmonella
      typhimurium in organs of pigs.
AB  - The aim of this study was to investigate the suitability of the invA-based
      polymerase chain reaction (PCR) assay for the specific detection of Salmonella in
      organs of experimentally infected pigs and to compare these results to classical
      bacterial culture. While the PCR conditions specified in the "Deutsche Industrie
      Norm", DIN 10135 (section 35 LMBG, 1999), cutle based on the publication of Rahn
      et al. 1992, revealed various unspecific amplification products, modifications of
      the PCR conditions allowed the specific amplification of the invA fragment from
      inner organs. The modified PCR assay correlates exactly with cultivation results
      (as required by DIN Norm 6579) and enables the detection of Salmonella within 48
      hours with equal sensitivity compared to routine cultivation.

PMID- 11570190
TI  - Sequence polymorphism of the Salmonella plasmid virulence factor D (SpvD) in
      Salmonella enterica isolates of animal origin.
AB  - The nucleotide sequence encoding the Salmonella plasmid virulence factor D (SpvD)
      was determined in 17 Salmonella strains that were different in O and H antigen
      patterns, animal host and geographical origin, and year of isolation. Nucleotide
      sequence comparison revealed the existence of at least nine spvD alleles
      resulting in 8 SpvD protein variants although the nucleotide sequences were
      highly similar (identity 98.8-100%). The spvD gene products differed from each
      other in up to 4 amino acid residues only with the exception of the carboxy
      terminally truncated SpvD variant of one S. Gallinarum field isolate. The highly
      conserved primary structure of SpvD in epidemiologically relevant salmonellae
      suggests that this virulence factor is a promising antigen candidate for
      diagnostic purposes (i.e. antibody detection in infected animals) but also for
      immunoprophylaxis in farm animal species.

PMID- 11570191
TI  - [Thromboembolism complications--most frequent cause of death after cesarean
      section].

PMID- 11570192
TI  - [Effect of thrombophilic factors on thromboembolism and other pregnancy
      complications].
AB  - Pulmonary embolism and/or deep vein thrombosis are a major cause of maternal
      mortality. In a number of adverse pregnancy outcome including preeclampsia,
      recurrent spontaneous abortion, restricted fetal growth and fetal death a role
      for thrombophilia (acquired and hereditable) has been postulated. Monitoring of
      acquired factors such as antiphospholipid-antibodies and hereditable factors
      (factor V Leiden, prothrombin mutation) may help predict the occurrence of
      pregnancy complications. Low molecular weight heparins (LMWH), since their
      introduction well established during pregnancy, and the rate of adverse fetal
      outcomes are related to co-morbidity maternal conditions rather than to the
      treatment itself. The use of LMWH is recommended for all moderate risk and high
      risk pregnant patients.

PMID- 11570193
TI  - [Preventive intravenous nitroglycerin administration in cesarean section to
      facilitate fetal extraction of infants between 500 and 1500 g--are there negative
      effects on the newborn infant?].
AB  - BACKGROUND: Preterm infants should be delivered with as little trauma as
      possible. Fetal extraction during cesarean delivery can be facilitated by
      modification of the incision or by use of short-term tocolytic agents. A possible
      alternative to intravenous administration of beta-mimetics is i.v. application of
      nitroglycerin to induce rapid uterine relaxation. This has been recommended by
      various clinical teams, but with relatively little experience being available
      regarding preterm births. PATIENTS AND METHODS: Retrospective analysis of the
      perinatal data for all single neonates weighing 500 to 1500 g delivered by
      cesarean section at the Berlin-Neukolln Hospital in the period from 6/1995 to
      9/1999 following prophylactic intraoperative i.v. application to the mother of
      0.2 mg nitroglycerin (n = 55). Control groups: 1. All infants weighing 500 to
      1500 g delivered by cesarean section at the Berlin-Neukolln Hospital with no
      intraoperative application of nitroglycerin (n = 38); 2. All infants weighing 500
      to 1500 g delivered by cesarean section included in Berlin perinatal statistics
      (BePE) 1993-1998 (n = 715). RESULTS: There were no differences between the groups
      in terms of Apgar scores or the incidence of arterial umbilical pH values < or =
      7.10 or of maternal blood loss > 1000 ml. Within the nitroglycerin group, in a
      shorter interval between nitroglycerin application and cutting of umbilical cord
      (< or = 3 min: n = 42; > 3 min: n = 13) 1-minute Apgar scores < 7 were observed
      more rarely, but no differences in arterial umbilical pH values < or = 7.10.
      CONCLUSIONS: 1. Intraoperative nitroglycerin application during cesarean section
      has no unfavorable effect on the condition of newborns < 32 SSW or between 500
      and 1500 g. 2. The incidence of intraoperative maternal blood loss > 1000 ml was
      not increased. 3. Differences in the interval between nitroglycerin application
      and cutting of the umbilical cord have no clinically relevant effects on Apgar
      scores or arterial umbilical pH.

PMID- 11570194
TI  - [Total cervix occlusion--an efficient measure in prolapsed amniotic membranes in
      extreme prematurity?].
AB  - BACKGROUND: We analysed retrospectively whether the total cervix occlusion
      implicates efficient the prolongation of pregnancy in patients with bulging fetal
      membranes during extreme prematurity. PATIENTS AND METHODS: Between 1993 and 1999
      nineteen pregnant women (17 singleton and 2 twin pregnancies) with cervical
      incompetence and bulging membranes at 20 to 27 weeks' gestation (mean 24 weeks)
      underwent total cervix occlusion (TCO) at the Department of Obstetrics at the
      Technische Universitat of Munich after taking cervical cultures, prophylactic
      antibiotic treatment, tocolysis and induction of fetal lung maturity (after 33
      weeks of gestational age). RESULTS: Eleven of nineteen pregnancies were carried
      beyond 32 weeks' gestation. 6 of 21 fetuses, included 2 twin pregnancies died.
      Considering the perinatal mortality the mean prolongation of pregnancy was 9.4
      weeks after total cervix occlusion. 9 of 19 pregnant women were delivered beyond
      37 weeks of gestational age. CONCLUSION: Taking the small number and the lack of
      a randomized trial into consideration, these results implicate the total cervix
      occlusion as an efficient method in cases of bulging membranes during extreme
      prematurity. Nevertheless a thorough postoperative control and screening of
      infectious complications are required.

PMID- 11570195
TI  - [Shorter delivery time after induction with misoprostol].
AB  - INTRODUCTION: Increasing evidence has demonstrated that intravaginal misoprostol
      (PGE1) is more effective in labor induction than dinoprostone (PGE2). Several
      studies have demonstrated that the administration of PGE1 instead of PGE2 reduces
      the induction-to-delivery interval. However, it has not been fully investigated
      on which phase of birth the activity of PGE1 is stronger than that of PGE2. We
      undertook this study to investigate whether the activity of the two
      prostaglandins are different over time during the induction-to-delivery interval.
      MATERIAL AND METHODS: 155 patients undergoing induction of labor with 50
      micrograms intravaginal PGE1 were compared with 174 patients treated with 3 mg
      PGE2. In both groups the procedure was repeated 6, and 24 hours after the first
      dose until labor was achieved. Induction-to-initiation of labor time, duration of
      labor stages, induction-to-delivery time, mode of delivery, maternal and neonatal
      morbidity and changes in Bishop score were compared. RESULTS: Demographic
      characteristics, indications for induction, mode of delivery, fetal weight,
      maternal and neonatal morbidity and duration of the labor stages were similar
      between the groups. A significant difference was found in terms of: induction-to
      initiation of labor interval (7.37 h [1-68] vs. 11.25 h [1-74], p < 0.01) and
      induction-to-delivery interval (11.5 h [2.5-89] vs. 14.4 h [2.7-94], p < 0.05).
      The Bishop score at the time of the second administration was significantly
      different from that at admission in the PGE1 group compared to the PGE2 group
      [PGE1: 4.8 +/- 2/5.6 +/- 1.9, p < 0.0005; PGE2: 3.9 +/- 2/4.2 +/- 1.4, p = 0.09].
      This effect of PGE1 remained significant after correction for various explanatory
      variables. CONCLUSIONS: The stronger effect of PGE1 is the consequence of a
      faster cervical ripening, which in turn leads to a quicker achievement of active
      labor. DISCUSSION: Intravaginal PGE1 compared to PGE2 reduces significantly the
      induction-to-delivery time.

PMID- 11570196
TI  - [Two-stage delivery after spontaneous rupture of fetal membranes and delayed
      abortion of the first twin in conservative management].
AB  - INTRODUCTION: 1-2% of all twin pregnancies are complicated by premature
      contractions, leading to premature rupture of membranes before 26 weeks of
      pregnancy. In this situation, a decision is required to either actively induce
      premature delivery or to initiate expectant management. Maternal and fetal risks
      regarding perinatal mortality and morbidity and the benefits of pregnancy
      prolongation have to be weighted against each other. CASE REPORT: We present
      delayed deliveries of two I-Parae with dichorionic twin pregnancies, achieved by
      in vitro fertilisation. In both cases, spontaneous membrane rupture and
      miscarriage of the leading fetus occurred prior to 20 gestational weeks. As signs
      of infection were missing initially, we adopted a conservative, expectant
      management. In both cases, the pregnancies could be prolonged to more than 30
      weeks' gestation. DISCUSSION: In the absence of additional risk factors,
      expectant, conservative management of multiple pregnancies after loss of one
      fetus can lead to pregnancy prolongation of 91 and 96 days, respectively. The
      gained gestational age of the remaining fetus and the healthy mother-child pairs
      are discussed under perinatal, economical and psychological aspects.

PMID- 11570197
TI  - [University medicine at the beginning of the 21st century. Attempt at a look into
      the future].

PMID- 11570198
TI  - [Standards in ultrasound examination in early pregnancy. Recommendation of DEGUM
      Stage III of the German Society of Ultrasound in Medicine (Gynecology and
      Obstetrics Section) and ARGUS (Working Group of Ultrasound Diagnosis of DGGG).
      December 2000 revision].

PMID- 11570199
TI  - Principles of stress fracture management. The whys and hows of an increasingly
      common injury.
AB  - As the patient population becomes more involved with athletics, informally or in
      an organized fashion, risk of stress fracture increases. Rapid and safe recovery
      is best ensured with early diagnosis and expedient conservative therapy. A
      history of progressive pain, initially with exertion and ultimately at rest,
      suggests the diagnosis. Plain radiographs often do not reveal fractures, and
      specialized studies, such as bone scanning, SPECT, or MRI, may be necessary to
      confirm the diagnosis. Simple rest with progressive reintroduction of activity is
      the treatment of choice for most stress fractures.

PMID- 11570200
TI  - Patient note: benign prostatic hyperplasia.

PMID- 11570201
TI  - Prioritizing pain management in patient care. Has the time come for a new
      approach.

PMID- 11570202
TI  - Do patients with somatization disorder want to be cured?

PMID- 11570203
TI  - The national epidemic of chronic kidney disease. What we know and what we can do.
AB  - The alarming increase in the incidence and mortality rate of end-stage renal
      disease (ESRD) over the past several years has prompted concerned physicians to
      ask why--and to ponder what can be done to ameliorate the situation. This
      article, the first in a seven-part series coordinated by the National Kidney
      Foundation, examines the factors surrounding the epidemic of chronic kidney
      disease and introduces readers to the organization's new clinical practice
      guidelines developed through its Kidney Disease Outcomes Quality Initiative.
      These recommendations emphasize early detection and treatment and offer a new
      avenue of communication between primary care physicians and nephrologists.

PMID- 11570204
TI  - Persistent localized rash after trauma. Infection or iatrogenic disease?

PMID- 11570205
TI  - Gastroesophageal reflux disease. Control of symptoms, prevention of
      complications.
AB  - GERD is a common disease that has a significant impact on patients' quality of
      life. Many surveys have shown that up to 60% of the population suffers from GERD
      at some time. Heartburn and acid regurgitation are the classic symptoms, but
      manifestations are variable. Of the several extraesophageal manifestations of
      GERD, reflux-induced asthma may be the most important. Complications of GERD
      include peptic strictures of the esophagus and Barrett's metaplasia. Clinical
      diagnosis of GERD can be confirmed by response to antisecretory therapy. A high
      dose trial of a PPI is becoming an accepted diagnostic technique for
      uncomplicated mild or moderate GERD. Endoscopic examination and ambulatory
      esophageal pH monitoring still have a role in the evaluation of severe GERD or
      when other diseases are suspected. Lifestyle changes rarely are beneficial, and
      antisecretory therapy remains the mainstay of GERD treatment. PPIs have been
      shown to be more effective than H2 blockers. Antireflux surgery is indicated in
      some patients. Healing of esophagitis can take up to 8 weeks; failure to control
      symptoms necessitates the use of higher drug doses. Failure to control symptoms
      with high-dose PPI treatment raises the likelihood of other causes.

PMID- 11570206
TI  - Another look at Barrett's esophagus. Current thinking on screening and
      surveillance strategies.
AB  - Barrett's esophagus remains a major health problem and a risk factor for the
      development of esophageal adenocarcinoma. Given the low incidence of this
      disorder, efforts should be made to identify risk factors that target patients
      with GERD or known Barrett's esophagus who would most benefit from screening and
      surveillance strategies. It is clear that identifying esophageal adenocarcinoma
      at an early and treatable stage reduces morbidity and mortality. However,
      currently available screening tools (endoscopy with surveillance biopsies every 2
      years) are expensive and not easily applied. Identification of tumor markers and
      other specific risk factors may be helpful in predicting who is at risk for
      dysplasia. Current therapeutic strategies are successful in the treatment of GERD
      symptoms, but further research and longer follow-up studies are needed to
      determine if these strategies bring about regression of Barrett's esophagus,
      reversal of dysplasia, or prevention of cancer.

PMID- 11570207
TI  - The role of H pylori in gastrointestinal disease. A guide to identification and
      eradication.
AB  - Helicobacter pylori, which is responsible for the most common infection
      worldwide, has been implicated in several gastrointestinal diseases, such as
      peptic ulcer disease, gastric adenocarcinoma, and mucosa-associated lymphoid
      tissue (MALT) lymphoma. In this article, Dr Knigge discusses the unique
      adaptation of H pylori to the acidic gastric environment and describes diagnostic
      tests to identify the organism, treatment recommendations, and tools to confirm
      eradication of infection.

PMID- 11570208
TI  - NSAID-related gastrointestinal injury. Evidence-based approach to a preventable
      complication.
AB  - NSAID-induced gastrointestinal mucosal injury and its subsequent complications
      are a tremendously important clinical problem. Effective prophylactic and
      treatment strategies involve proton pump inhibitors, misoprostol, or selective
      COX-2 inhibitors. These agents are capable of dramatically decreasing or
      eliminating the risk of mucosal injury as well as the morbidity and mortality for
      this disorder. Identification of the at-risk patient and initiation of
      appropriate preventive therapy are the keys to minimizing the societal burden of
      this disease process.

PMID- 11570209
TI  - Optimizing the latest neuroradiology tools. New techniques are particularly
      useful in stroke management.
AB  - In the past several years, advances in central nervous system imaging and
      interventional techniques have directly and dramatically improved healthcare. In
      this article, Drs Naul and Santiago discuss developments in magnetic resonance
      imaging (MRI) and interventional neuroradiology. In addition, the role of these
      techniques in the management of strokes is highlighted.

PMID- 11570210
TI  - [Economic assessment of iron deficiency. Replacement of ferritin and serum iron
      by other parameters].
AB  - Economic assessment of iron deficiency. Replacement of serum iron and ferritin by
      other parameters. Serum iron and ferritin are still widely used parameters for
      the assessment of iron deficiency, in spite of their poor diagnostic performance.
      Compared to the combined use of ferritin, zinc protoporphyrin and soluble
      transferrin receptors an increase of the percentage of hypochromic erythrocytes
      (PEH) was found to be highly sensitive and specific for iron deficiency. We
      suggest to use it in a two phase strategy. Normal PEH excludes iron deficiency.
      Increased PEH may be confirmed by zinc protoporphyrin and/or soluble transferrin
      receptors.

PMID- 11570211
TI  - [Lipiwatch: a study of the treatment of dyslipidemias in Luxembourg].
AB  - LIPIWATCH is an observational study which has been initiated for 6 months in
      Belgium and in Luxembourg in 1997 to evaluate if patients treated by lipid
      lowering drugs could reach the recommendations of the EAS and NCEP II for LDL-C.
      76 patients (31 men) with a mean age of 59.2 +/- 11.39 years were included. 96%
      of patients had at least one other associated cardiovascular risk factor. After 6
      months of treatment, 33% of all patients and only 30% of patients with coronary
      heart disease or peripheral vascular disease or at least 2 other risk factors
      reached the recommendations of the EAS. 25% of all patients and only 20% of
      patients with known coronary heart disease reached the NCEP II recommendations.
      55% of patients had a statin prescribed and 38% a fibrate. Mean total cholesterol
      and mean LDL-C was lowered by 20% and 19% after 6 months. These disappointing
      results confirmed an insufficient awareness by physicians and patients,
      inadequate dosages of drugs and a bad compliance by patients.

PMID- 11570212
TI  - A Merkel cell carcinoma of the skin.
AB  - A 79-year old female caucasian patient presented in January 91 with a nodular
      lesion of the right cheek that had appeared rapidly. The histologic specimen was
      in favour of a primary neuroendocrine skin tumor, Merkel cell carcinoma-. In
      March 91, a relapsing nodule had grown up and adenopathies were found on the
      right parotid and sub-mandibular spaces. An aggressive polychemotherapy was
      performed for 6 cycles and a complete remission was obtained. In November 91 the
      sub-mandibular lymph node had reappeared. A complete staging was again performed.
      After 3 cycles of chemotherapy, a regional radiotherapy completed the treatment.
      With a follow-up of more than 8 years the patient stays in complete remission in
      April 2000.

PMID- 11570213
TI  - [Salmonella infections in swine. Salmonella infections in swine in meat hygiene].
AB  - Salmonella is considered one of the most important food borne pathogens that has
      potential implications for human health. In Germany, Salmonella monitoring is
      being used in swine farms as a predictor for Salmonella infection and to
      implement control measures directed to minimise cross-contamination at the
      slaughter plant. An research project was established in order to gain experience
      with the eradication of Salmonella in German swine herds.

PMID- 11570214
TI  - [Quality evaluation of the orthodontic practice for certification by ISO 9001. A
      procedure beneficial for medical, medico-dental or hospital service].
AB  - The accreditation of the ISO 9001 certification (ISO = International Standard
      Organization) is an external evaluation procedure carried out by independent
      experts, whose object is the analysis of the operational methods and practices of
      a medical care facility (e.g. hospital, private clinic, general practitioner's or
      dentist's practice) which decided to assume the concept, implementation and
      control of its own quality policy. The whole accreditation procedure represents
      the basic structure of a continuous dynamic progressiveness within a cabinet
      eager to offer outstanding quality. Moreover, it guarantees active and voluntary
      participation of every single member of the medical administration or technical
      team involved in the realization of this primary objective. In other words, we
      are talking about a very strong dynamic innovation leading to a change of views
      and the improvement of communication means, while simultaneously enhancing the
      security and quality aspects of medical care. The continuous guarantee of high
      quality medical care calls for precise planning and systematization of actions.
      First of all, these actions are defined, analyzed and listed in precise work
      procedures. As they are defined with the agreement of the whole team, they
      implicate respect and self control. This requires of course transparency of the
      treatment methods, whose different steps and procedures are described in detail
      in a logogramm set up in common.

PMID- 11570215
TI  - Simple and convenient preparation of 1-(arylamino)methylbenzotriazoles and 
      (arylamino)methylbenzimidazoles.
AB  - The preparation of 1-(arylamino)methylbenzotriazoles 1a-17a and benzimidazoles 1b
      17b is described and their antibacterial activity evaluated. 1
      Hydroxymethylbenzazo-les react with the appropriate aniline to yield the target
      compounds. These were characterized using 1H NMR, IR, UV spectra. The compounds
      displayed no significant antibacterial activity.

PMID- 11570216
TI  - Synthesis of some new derivatives of thiazolo-[3,2-a]pyrimidine-3,5,7(2H)-trione
      of potential biological activity.
AB  - A number of 6-(m-tolylazo)-thiazolo[3,2-a]pyrimidine-3,5,7(2H)-trione (3), 2,6
      di(m-tolylazo)thiazolo[3,2-a]pyrimidine-3,5,7(2H)-trione (4), thiazolo[3,2
      a]pyrimidine-3,5,7-trione (5) and 2-(m-tolylazo)thiazolo[3,2-a]pyrimidine
      3,5,7(2H)-trione (6) here been prepared. The structure of the new ring system
      have been confirmed by IR and 1H-NMR spectral data.

PMID- 11570217
TI  - Preparation and antibacterial evaluation of some nitrone derivative and their
      zirconium (IV) chloride complexes.
AB  - Some new complexes of the general formula ZrCl3.L where L = [N-(p-anisole)-alpha
      (2-xanthatophenyl)nitrone], L1, and [N-(p-chlorophenyl)-alpha-(2
      xanthatophenyl)nitrone], L2, have been prepared and characterized by elemental
      analysis, i.r. and molar conductances. The antibacterial activities of these
      compounds have been studied against five species of bacteria in vitro at
      concentration ranging from 1-10 micrograms/ml. A remarkable activity was
      exhibited by the ligand L2 against Staph. aureus and Bacillus subtilis.

PMID- 11570218
TI  - Studies on the synthesis and biological activity of 3-arylaminomethyl-5-(3
      pyridyl)-1,3,4-oxadiazole-2-thione derivatives.
AB  - 3-arylaminomethyl-5-(3-pyridyl)-1,3,4-oxadiazole-2-thiones were prepared by
      reaction of 5-(3-pyridyl)-1,3,4-oxadiazole-2-thione with formaldehyde and
      appropriate alky and aryl amines in ethanol, as potential biological active
      agents. These new synthesized Mannich bases were screened for their
      antimicrobial, antifungal and antiinflammatory activities.

PMID- 11570219
TI  - Synthesis and biological activity of 2-thiono-[1H]-5-spirocyclohexylimidazo[4,3
      b]quinazolone and 8-azaquinazolone derivatives.
AB  - The reaction of 5-spirocyclohexylimidazole-2,4-dithion with one and two mole
      equivalent of b-aminocarboxylic acid derivatives (2a-b and 5) to give new
      heterocyclic systems of synthetic and potential biological interest viz.
      compounds (3a-b, 4a-b, 6 and 7). The structures of the products have established
      by chemical and spectroscopic evidence. The antimicrobial activity of the
      synthesized compounds was tested against 10 bacterial and yeast strains.

PMID- 11570220
TI  - Synthesis and antibacterial activity of pyridyl thioureas and
      arylthiosemicarbazones.
AB  - [N-(2-pyridyl)-N'-(4-(un) substituted] thioureas and
      (substitutedaryl)thiosemicarbazones were synthesised and evaluated for their
      antibacterial activity. All aryl thiosemicarbazones showed good activity against
      Aeromonas hydrophilia and Salmonella typhimurium. But none of the pyridyl
      thioureas showed any prominent activity against tested bacteria.

PMID- 11570221
TI  - Fused cinnolines: synthesis and biological activity.
AB  - Cinnolines, in general, have been reviewed in details over the last decades.
      Fused cinnolines have shown remarkable biological activities. Some fused
      cinnolines received approval as bioactive drug or still in advanced clinical
      trials. This is prompted the need to review fused cinnolines from the synthetic
      and biological points of view.

PMID- 11570222
TI  - Interactions of tryptophan and serotonin with biomembrane models: binding to
      reversed micellar systems of ionic and non ionic surfactants.
AB  - The interactions of Tryptophan (TRP) and Serotonin (5-HT), with water-containing
      sodium bis (2-ethylhexyl) sulfosuccinate (AOT), didodecyldimethylammonium bromide
      (DDAB) and tetraethylene glycol monododecyl ether (C12E4) reversed micelles have
      been investigated by UV absorption spectroscopy. Our results suggest that
      independently of the nature of the surfactant and the amount of the water
      encapsulated into the micellar core, TRP and 5-HT are solubilized in the micellar
      phase, preferring to be located in a shallow region constituted by the hydrated
      surfactant head groups. This is due to the amphiphilic nature of TRP and 5-HT and
      the biological implications are discussed.

PMID- 11570223
TI  - Determination of phenolphthalein and methylene blue by first derivative
      spectrophotometry and potassium nitrate by direct spectrophotometry in a
      pharmaceutical formulation.
AB  - A rapid first derivative visible spectrophotometric determination is described
      for the simultaneous determination of phenolphthalein (PHP) and methylene blue
      (MB) in the presence of potassium nitrate (KNO3). Potassium nitrate is also
      determined by direct visible spectrophotometric method in the presence of
      phenolphthalein and methylene blue without any interference. The methods have
      been applied to the determination of the three compounds in a commercial dosage
      form. The calibration graphs were linear in the range of 0.30-3.20 mg mL-1 for MB
      and 0.80-3.18 micrograms mL-1 for PHP and 0.80-8.10 micrograms mL1 for KNO3. The
      specificity, accuracy and precision of the methods have been assessed.

PMID- 11570224
TI  - Chemical constituents of Artemisia inculta.

PMID- 11570225
TI  - A new type of tyrosinase inhibitors from natural products as potential treatments
      for hyperpigmentation.
AB  - Selected flavonoids were evaluated for their effects on melanin biosynthesis by
      using mushroom-tyrosinase assay. Out of 27 tested flavonoids, only six showed a
      potential inhibitory activity on melanin biosynthesis. Flavonoids containing an
      alpha-keto group showed to be the active compounds in this assay. This may be
      explained in terms of similarity between the dihydroxyphenyl group in L-DOPA and
      the alpha-ketol group in flavonoids. The results of this study revealed a new
      type of tyrosinase inhibitor from natural origin. These compounds will be further
      examined for their application for treatment of hyperpigmentation problems e.g.
      melasma and ephelides.

PMID- 11570226
TI  - Analysis of the drugs, applied for the treatment of the patients, hospitalized in
      a urological department, by pharmacological groups.
AB  - The analysis of the drugs, applied for the treatment of the hospitalized patients
      in a urological department shows that the application of the drugs in a
      urological department gives the opportunity to stop the process of the
      development of the disease and to avoid the hospitalization of the patients. The
      research shows the different pharmacological groups of drugs that are applied and
      also the expenses that are made for the treatment of the patients.

PMID- 11570227
TI  - Reimbursed treatment, regulated in the national frame contract.
AB  - The investigation is an analysis of the main elements, included in the
      reimbursement system for the drug insurance. The aim is directly dependent on the
      valuation for the adequate service of the arise health needs of the citizens that
      are obligatory insured. The used methods are connected with an analysis of the
      regulations and of the statistical information. As result of the investigation
      are characterized the seize of the disease and of the drug nomenclature with a
      forecast reimburse therapy. The provide valuation of the objective state of the
      system shows that the criteria and rules are not clear and precise in respect of:
      the include of the drugs in the positive list, the determination of the level of
      reimbursement, the selection of the disease with the reimbursement treatment and
      especially of those with totally reimbursed therapy. The investigation shows that
      the accepted principles in this area are appropriate with the modern concepts and
      tendencies, but for their real realization are necessary additional attempts for
      overcoming of the negatives in the process of developments through adequate
      administrative decisions and approaches.

PMID- 11570228
TI  - The power of statistical tests in meta-analysis.
AB  - Calculations of the power of statistical tests are important in planning research
      studies (including meta-analyses) and in interpreting situations in which a
      result has not proven to be statistically significant. The authors describe
      procedures to compute statistical power of fixed- and random-effects tests of the
      mean effect size, tests for heterogeneity (or variation) of effect size
      parameters across studies, and tests for contrasts among effect sizes of
      different studies. Examples are given using 2 published meta-analyses. The
      examples illustrate that statistical power is not always high in meta-analysis.

PMID- 11570229
TI  - Moderated multiple regression for interactions involving categorical variables: a
      statistical control for heterogeneous variance across two groups.
AB  - Moderated multiple regression (MMR) arguably is the most popular statistical
      technique for investigating regression slope differences (interactions) across
      groups (e.g., aptitude-treatment interactions in training and differential test
      score-job performance prediction in selection testing). However, heterogeneous
      error variances can greatly bias the typical MMR analysis, and the conditions
      that cause heterogeneity are not uncommon. Statistical corrections that have been
      developed require special calculations and are not conducive to follow-up
      analyses that describe an interaction effect in depth. A weighted least squares
      (WLS) approach is recommended for 2-group studies. For 2-group studies, WLS is
      statistically accurate, is readily executed through popular software packages
      (e.g., SAS Institute, 1999; SPSS, 1999), and allows follow-up tests.

PMID- 11570230
TI  - Assessing program effects in the presence of treatment-baseline interactions: a
      latent curve approach.
AB  - Methods for assessing treatment effects of longitudinal randomized intervention
      are considered. The focus is on modeling the nonlinear relationship between
      treatment effects and baseline often observed in prevention programs designed for
      at-risk populations. Piecewise linear growth modeling was used to study treatment
      effects during the different periods of development. A multistep multiple-group
      analysis procedure is proposed for assessing treatment effects in the presence of
      nonlinear treatment-baseline interactions. Standard errors of the estimates from
      this multistep procedure were obtained using a bootstrap approach. The methods
      are illustrated using data from the Johns Hopkins Prevention Research Center
      involving an intervention aimed at improving classroom behavior.

PMID- 11570231
TI  - Testing parameters in structural equation modeling: every "one" matters.
AB  - A problem with standard errors estimated by many structural equation modeling
      programs is described. In such programs, a parameter's standard error is
      sensitive to how the model is identified (i.e., how scale is set). Alternative
      but equivalent ways to identify a model may yield different standard errors, and
      hence different Z tests for a parameter, even though the identifications produce
      the same overall model fit. This lack of invariance due to model identification
      creates the possibility that different analysts may reach different conclusions
      about a parameter's significance level even though they test equivalent models on
      the same data. The authors suggest that parameters be tested for statistical
      significance through the likelihood ratio test, which is invariant to the
      identification choice.

PMID- 11570232
TI  - Bidirectional experimental effects.
AB  - Bidirectional experimental effects cannot be demonstrated by comparing measures
      of central tendency. Three approaches to the problem were considered: a test of
      homogeneity of variance, a comparison of control and experimental quartile
      frequencies by means of the chi-square test of association, and the cumulative
      percentage-difference (CPD) curve--a graphic tool for demonstrating bidirectional
      effects. Two tests of significance were developed based on the CPD curve's
      maximum and minimum values. All 3 tests were first put to use analyzing simulated
      data, which incorporated 6 different patterns of experimental effect. The results
      of 100 repetitions of the simulations are summarized. Next, the results of a
      lexical-decision experiment with partial-word preview were analyzed using the
      procedures considered. The report ends with a presentation of guidelines for the
      use of the bidirectional tests.

PMID- 11570233
TI  - Mixed-model pairwise multiple comparisons of repeated measures means.
AB  - One approach to the analysis of repeated measures data allows researchers to
      model the covariance structure of the data rather than presume a certain
      structure, as is the case with conventional univariate and multivariate test
      statistics. This mixed-model approach was evaluated for testing all possible
      pairwise differences among repeated measures marginal means in a Between-Subjects
      x Within-Subjects design. Specifically, the authors investigated Type I error and
      power rates for a number of simultaneous and stepwise multiple comparison
      procedures using SAS (1999) PROC MIXED in unbalanced designs when normality and
      covariance homogeneity assumptions did not hold. J. P. Shaffer's (1986)
      sequentially rejective step-down and Y. Hochberg's (1988) sequentially acceptive
      step-up Bonferroni procedures, based on an unstructured covariance structure, had
      superior Type I error control and power to detect true pairwise differences
      across the investigated conditions.

PMID- 11570234
TI  - Statistical properties of the rWG(J) index of agreement.
AB  - L. R. James, R. G. Demaree, and G. Wolf (1984) introduced rWG(J) to estimate
      interrater agreement for a group. This index is calculated by comparing an
      observed group variance with an expected random variance. As researchers have
      gained experience using this index, several questions have arisen. What are the
      consequences of replacing values beyond the unit interval by 0? What is the
      dependence of rWG(J) on the group size? The authors' simulations show that a
      positive bias is caused by the truncation, but for large population values of
      rWG(J) it is negligible. Also, in this case, the group size has no effect on the
      expected value of rWG(J). For inference on rWG(J), researchers can exploit the
      availability of computers to simulate data from the hypothesized distribution and
      then compare the simulation results for rWG(J) with the actual values. In
      addition, it is shown how the bootstrap method can be used for comparing the
      indices of 2 groups.

PMID- 11570235
TI  - [MR angiography: technical principles and uses in the diagnosis of neurological
      diseases].
AB  - During the last decade, magnetic resonance angiography (MRA) has been
      incorporated into the routine evaluation of patients with suspected
      cerebrovascular disease. Although digital subtraction angiography (DSA) is still
      the gold standard in diagnostics of intracranial vascular disease, it has been
      replaced by MRA in numerous clinical applications. In this paper we first provide
      a review of the various MRA techniques. In the second part, the diagnostic value
      as well as advantages and disadvantages of the different techniques are assessed
      for various cerebrovascular diseases, such as vessel occlusion, stenosis,
      dissection, cerebral aneurysms, and spinal and cerebral arteriovenous
      malformations.

PMID- 11570236
TI  - MR-venography using high resolution True-FISP.
AB  - A new fast MR-venography approach using a high resolution True-FISP imaging
      sequence was investigated in 20 patients suffering from 23 deep vein thromboses.
      Diagnosis was proven by x-ray venography, CT or ultrasound examination. The
      presented technique allowed for clear thrombus visualization with a high contrast
      to the surrounding blood pool even in calf veins. Acquisition time was less than
      10 minutes for imaging the pelvis and the legs. No contrast media was needed. The
      presented high resolution True-FISP MR-venography is a promising non-invasive,
      fast MR-venography approach for detection of deep venous thrombosis.

PMID- 11570237
TI  - [Comparison of iodinated and barium-containing contrast media of different
      viscosity in the detection of pharyngeal perforation].
AB  - PURPOSE: In contrast to esophageal perforations, the more radiopaque barium
      suspensions are not as important as iodinated aqueous contrast agents for the
      detection of pharyngeal perforations. This study was performed to find out
      whether the highly different viscosities (of iodinated and barium-containing
      contrast agents with comparable radiopacities) are a reason for this. METHODS:
      Viscosity, subjective difference in contrast, and CT-density of an iodinated
      aqueous (Telebrix) and a 50 wt/vol% barium-containing contrast agent (Micropaque)
      were determined. Moreover, to exclude postoperative perforation, 104 patients
      were prospectively examined by pharyngography using both contrast media.
      Pharyngographies of patients with perforation were later compared by two
      independent readers. All patients with perforation were followed up clinically to
      exclude complications due to barium administration. RESULTS: In-vitro comparison
      showed comparable radiopacity but the 50 wt/vol% barium-suspension was much more
      viscous than the iodinated contrast agent. During pharyngography, totally, 14
      perforations were clearly delineated with the iodinated aqueous contrast agent.
      However, two of them were not detected with the barium-suspension. All the other
      perforations presented equally. CONCLUSIONS: Given a sufficient radiopacity, a
      low viscosity appears to be essential for a contrast agent to detect especially
      pharyngeal perforations. Thus, we recommend the sole use of an iodinated contrast
      agent (at suspicion of aspiration as isoosmolar variant) for this purpose.

PMID- 11570238
TI  - [Stereotactic vacuum core biopsy of clustered microcalcifications classified as
      B1-RADS 3].
AB  - PURPOSE: Evaluation of stereotactic vacuum core biopsy of clustered
      microcalcifications categorized as BI-RADS 3. MATERIAL AND METHODS: 86 patients
      with microcalcifications BI-RADS 3 (probably benign, < 3% malignant) underwent a
      stereotactic vacuum core biopsy (Mammotome, Fa. Ethicon Endo-Surgery Breast Care)
      using a digital stereotactic unit (Mammotest, Fa. Fischer Imaging). The removal
      of the calcifications was judged by two radiologists in consensus and classified
      as complete (100%), major (55-99%) or incomplete (< 50%). RESULTS: 4/86 patients
      could not be evaluated by vacuum core biopsy due to the localization of the
      microcalcifications close to the skin or lack of detection. In 40/82 cases a
      complete, in 38/82 a major, and in 4/82 a incomplete removal was achieved.
      Histology revealed 67 cases of fibrocystic changes, 4 papillomas, 4
      fibroadenomas, 4 cases of atypical ductal hyperplasia (ADH), and 3 ductal
      carcinomas in situ (DCIS), one of these with a minimal-invasive tumor component.
      Patient with ADH were advised to undergo surgical biopsy. Histology revealed
      complete removal. 7 patients had complications or side-effects. CONCLUSIONS:
      Percutaneous vacuum core biopsy is a reliable minimal-invasive diagnostic method
      to come to the final diagnosis in patients with clustered microcalcifications
      categorized BI-RADS 3. However, if malignancy is proven (about 4% of our cases)
      an open biopsy is necessary.

PMID- 11570239
TI  - [Magnetic resonance imaging and magnetic resonance arthrography of the acetabular
      labrum: comparison with surgical findings].
AB  - AIM OF THE STUDY: To evaluate the accuracy of magnetic resonance imaging (MRI)
      and magnetic resonance (MR) arthrography in detecting acetabular labral lesions
      in correlation to surgical findings. PATIENTS AND METHODS: Forty patients (40
      hips) with chronic hip pain and a strong clinical suspicion of labral lesions
      were examined with MRI in the coronal and axial plane by obtaining T1 weighted
      and proton density-weighted spin echo sequences. Additionally, MR arthrography of
      the hip joint in the coronal oblique and sagittal oblique plane was performed by
      obtaining T1-weighted three-dimensional gradientecho sequences after the
      intraarticular injection of gadopentate dimeglumine. The labra were prospectively
      evaluated on the basis of morphology, signal intensity, the presence or absence
      of a tear, and their attachment to the acetabulum. All patients underwent
      surgery, and the MRI findings and MR arthrography findings were compared with the
      surgical results. RESULTS: Surgically, 34 labral lesions, and 6 normal labra were
      detected. MRI correctly depicted labral lesions in 24 patients and two normal
      labra, and MR arthrography correctly depicted labral lesions in 30 patients and 5
      normal labra compared with the surgical results. The sensitivity of MRI was 80%,
      the accuracy of MRI was 65%, the sensitivity of MR arthrography was 95%, and the
      accuracy of MR arthrography was 88%. CONCLUSIONS: MR arthrography enables
      considerably more accurate detection of acetabular labral lesions than MRI. MR
      arthrography should be the method of choice for the diagnosis of the presence or
      absence of acetabular labral lesions in patients with chronic hip pain and a
      strong clinical suspicion of labral lesions.

PMID- 11570240
TI  - [CT-guided therapy of osteoid osteoma by drill trepanation of the nidus. Clinical
      follow-up results].
AB  - PURPOSE: Evaluation of technical success and follow-up of patients with osteoid
      osteoma. MATERIAL AND METHODS: 9 patients (3 w, 6 m) with a mean age of 22.3
      years suffering from an osteoid osteoma localized in the femur were treated with
      a combination therapy based on drill trepanation of the nidus and subsequent
      installation of 1-2 ml ethanol (96%). The treatment was done under CT-guidance in
      general anaesthesia. RESULTS: During the follow-up period of 20.6 months (10 to
      39 months) one relapse occurred within 3 months. This was treated with the same
      percutaneous method. CONCLUSIONS: Percutaneous removal of intracortical osteoid
      osteomas under CT-guidance had success in this study, was technical easy, and a
      had low relapse rate. In addition the duration of hospitalisation is shorten.
      Meanwhile other studies have used additive ablation with radiofrequency. A second
      study has been started in our department using a thermoablative procedure. In a
      comparison between surgical and radiological methods, the rates of relapse are
      similar (9% vs. 23% surgically). The CT-guided removal of intracortical osteoid
      osteomas should be the procedure of first choice.

PMID- 11570241
TI  - [Panorama ultrasonography of the abdominal wall for delineation of the anatomy
      and diagnosis of pathological findings].
AB  - PURPOSE: To assess extended field-of-view sonography for delineation of the
      anatomic structures of the abdominal wall and for the diagnosis of hernia.
      MATERIAL AND METHODS: In 34 cases (24 probands, 10 patients with abdominal wall
      defects) extended field-of-view sonography of the abdominal wall was performed
      with a 7.5 MHz transducer. Dynamic alignment of real-time images allows for
      depiction of regions of up to 60 cm in a single extended field-of-view image. A
      standardized axial image was obtained above and below the arcuate line and at the
      level of the defect, respectively. All images were evaluated by two blinded
      readers regarding the visibility of the anatomic structures and the delineation
      and extent of pathological changes. RESULTS: The abdominal wall was delineated
      with extended field-of-view sonography in all patients with a good image quality.
      The linea alba, the rectus muscle and the three lateral abdominal muscles, the
      rectus sheath, the peritoneum, and the subcutaneous fatty tissue were visible. In
      the patients with abdominal wall defects, the hernial sac with its contents, the
      extension of the defect, and the surrounding structures were clearly delineated.
      CONCLUSION: Extended field-of-view sonography allows for easily surveyed and
      reproducible documentation of the ultrasound examination of the abdominal wall.
      It is especially useful for the preoperative planning in patients with abdominal
      wall defects.

PMID- 11570242
TI  - [Abscesses after appendectomy due to intraoperative retaining of fecalith].
AB  - OBJECTIVE: Fecaliths appear to predispose a patient to acute appendicitis,
      abscess formation, and perforation. The number of preoperative radiological
      evaluations is increasing, although children with suspected perforation still
      undergo surgery immediately. We report and discuss imaging findings and
      implications in children with acute appendicitis and fecaliths. METHODS: Four
      children (3 girls, 1 boy; mean age 9 years) underwent surgery for acute
      appendicitis. Three children underwent sonography and plain radiography before
      surgery, 1 child was operated without radiological evaluation. After readmission,
      all 4 children underwent sonography and plain radiography before surgery.
      RESULTS: In 3 patients a fecalith was diagnosed initially. After uneventful
      recovery all 4 patients had acute abdominal pain and readmission was necessary.
      In all 4 patients the escaped fecalith was demonstrated with sonography and plain
      radiography confirmed surgically. CONCLUSION: Discussion about the role of
      imaging in acute appendicities has concentrated on the diagnostic yield of cross
      section techniques. The importance of demonstrating a fecalith, prompting a more
      thorough intraoperative search has found little attention. The radiologist should
      also detect and localize a fecalith and should be aware of retained fecaliths as
      a cause of abscess formation after appendectomy.

PMID- 11570243
TI  - [Prospective study to compare high-resolution computed tomography and magnetic
      resonance imaging in the detection of pancreatic neoplasms: use of intravenous
      and oral MR contrast media].
AB  - PURPOSE: To compare thin-section hydro-CT and MRI in the detection of pancreatic
      neoplasms. Evaluation of an oral, superparamagnetic contrast agent (OMP) for
      pancreatic MRI. MATERIAL AND METHODS: 45 patients with suspected pancreatic
      neoplasms were examined with consecutive thin-section helical CT (Hydro-CT,
      3/6/3, 130 ml Ultravist, Schering) and MRI (1.0 T, breath-holding, T1w-GRE, T1w
      GRE fat-sat, T2w-TSE). The MRI protocol included precontrast studies, studies
      after oral administration of OMP (Abdoscan, Nycomed Amersham) and studies after
      administration of OMP and Gadodiamide i.v. (Omniscan, Nycomed Amersham). All
      images were assessed by two independent radiologists in a blinded fashion.
      Radiologic diagnosis was correlated with histology or clinical follow-up (> or =
      3 month). RESULTS: 39 patients could be included in analysis. In 13 cases a
      pancreatic neoplasm was proven by histology. Thin-section hydro-CT and MRI showed
      no statistically significant differences for the detection of pancreatic
      neoplasia. The sensitivity of helical hydro-CT was superior compared to MRI
      (88.5% vs. 65.44/73.1%/76.9%). The specificity of MRI was superior compared to
      helical hydro-CT (86.5% vs. 94.2%/90.4%/88.5%). CONCLUSION: Thin-section hydro-CT
      and MRI show similar results for the detection of pancreatic neoplasms. Compared
      to thin-section helical CT, MRI still has the drawbacks of much more time
      consumption and, still, lower spatial resolution. The use of an oral,
      superparamagnetic contrast agent added no advantage for pancreatic MRI.

PMID- 11570245
TI  - [Radiologic diagnosis of fistulas and abscesses in Crohn's disease: cost
      effectiveness analysis of 2 different imaging strategies].
AB  - PURPOSE: To analyze cost-effectiveness of magnetic resonance imaging and
      conventional enteroclysis in the assessment of fistulas and abscesses in patients
      with Crohn's disease (CD). METHODS: A decision analytic model was used to compare
      enteroclysis with MRI, performing a cost-effectiveness analysis of both
      diagnostic strategies. Data from 84 patients undergoing a clinical trial were
      used. Primary outcome was defined as one correctly diagnosed patient regarding
      Crohn's disease, fistulas, and abscesses, including true-positive and true
      negative cases. Costs of the two procedures were estimated in German Marks (DM)
      using fee schedules. The influence of different definitions of effects was
      calculated. For all variables single and multiple sensitivity analyses were
      performed. RESULTS: Incremental cost effectiveness of MRI vs. enteroclysis was
      3,119.33 DM per one additional correctly diagnosed patient. The results of
      sensitivity analyses suggest that MRI use in certain patient subgroups (patients
      at higher prevalence of CD, fistulas, and abscesses) even becomes more cost
      effective. In this case one additional effect could be gained below 1,650 DM.
      CONCLUSIONS: From an economic perspective, decision makers should consider the
      use of MRI in the work-up of patients with Crohn's disease as an efficient
      procedure under certain conditions. To support treatment policies for physicians
      or insurance coverage of certain diagnostic strategies the costs possibly saved
      with MRI should also be considered.

PMID- 11570244
TI  - [Hydro-MRI in inflammatory bowel diseases: a comparison with colonoscopy and
      histology].
AB  - PURPOSE: To compare hydro-MRI with colonoscopy and biopsy specimen regarding the
      assessment of inflammatory activity and the differentiation of inflammatory bowel
      diseases. MATERIAL AND METHODS: After an oral bowel opacification using 1000 ml
      of a 2.5% mannitol solution and a rectal bowel opacification using 250-500 ml of
      a 0.9% saline solution, axial and coronal breath-hold sequences +/- Gd-DTPA
      (HASTE-["half-Fourier acquisition single-shot turbo spin echo"] and dynamic FLASH
      ["fast low angle shot"]) were acquired in 27 patients with inflammatory bowel
      disease. The enhancement of the bowel wall as well as morphological MRI findings
      were correlated with colonoscopy and biopsy specimens. By means of the MRI
      findings, Crohn's disease (CD) and ulcerative colitis (UC) should be
      differentiated. RESULTS: In CD, a significant correlation between the contrast
      enhancement of the inflamed bowel wall (delta SI) and the
      endoscopic/histopathologic indices could be established (r = 0.52; p = 0.02 and r
      = 0.72; p = 0.001). In UC, no correlations between delta SI and the
      endoscopic/histopathologic indices could be found. The correct diagnosis of CD
      and UC by MRI findings was possible in 22/27 patients (81%). CONCLUSION: Hydro
      MRI with dynamic studies is suitable for the assessment of disease activity in
      CD, but unreliable in UC. Hydro-MRI provides useful information for the
      differentiation of CD and UC.

PMID- 11570246
TI  - [Diagnostic value of different rectal contrast media in the detection of
      colorectal diseases by multi-slice CT].
AB  - PURPOSE: Assessment of 3 different rectal contrast agents (water,
      methylcellulose, ultrasound gel) for their suitability for colorectal imaging in
      multislice CT (MS-CT). METHODS: 115 patients with colorectal diseases underwent
      MS-CT with varying, rectal contrast agents in a prospective study. Images were
      assessed by 2 independent CT-experienced radiologists. 6 criterias were
      evaluated, using a 5-point scale. RESULTS: Methylcellulose (MC) proved to be
      significantly superior to ultrasound gel (US). Especially, differentiation of
      healthy and diseased bowel and bowel wall and lumen were aided, which was proven
      by quantitative analysis of attenuation values. Rectal distension is greater
      using MC or US than for water. More proximal parts of the colon could be better
      distended with water. The interobserver correlation was good (kappa 0.76).
      CONCLUSIONS: Rectal filling with MC significantly improves diagnostic confidence
      in colorectal examinations. Ease of administration and lack of problems suggest
      its use as a clinical routine tool.

PMID- 11570247
TI  - [Body structure and radiation exposure in dynamic X-ray studies. A contribution
      to determining national reference values].
AB  - PURPOSE: To contribute data on radiation exposure in dynamic X-ray procedures and
      to compare them with anthropometric parameters. METHODS: 50 venographies of the
      lower extremity, 51 abdominal arteriographies, and 121 double contrast
      examinations of the small bowel were carried out and the dose-area product (DAP)
      measured for each of the procedures. Additionally, fluoroscopy time, number of
      shots, body height, body weight, and the sagittal diameter of the examined region
      were recorded. Dose measurements were statistically evaluated and the following
      data determined: Frequency distribution, mean, median, 25%- and 75 percentiles as
      well as correlations with sex, body weight, and diameters. RESULTS: Median DAP
      was 587 (men: 540; women: 636) cGycm2 with venography of the lower extremities.
      DAP/min was better correlated with body weight (r = 0.663) than with diameters of
      the thigh (r = 0.611). Mean DAP was 14,869 (18,070; 10,980) cGycm2 with abdominal
      arteriography. DAP/min was badly correlated both with body weight (r = 0.285) and
      diameters of the abdomen (r = 0.249). Mean DAP was 4527 (5096; 4114) cGycm2 with
      enteroclysis. DAP/min was well correlated with both body weight (r = 0.621) and
      diameters of the abdomen (r = 0.628). CONCLUSION: DAP of venography of the lower
      extremity and enteroclysis is greatly influenced by the constitution of the
      patient. The differences between men and women are, however, not as striking as
      with static X-ray procedures. By contrast, in abdominal arteriography body weight
      and diameter play a limited role for radiation exposure.

PMID- 11570248
TI  - [Interventional-radiologic emergency therapy in bleeding hemangiosarcoma of the
      liver].

PMID- 11570249
TI  - [Intramural bile duct varicosis ("pseudo-cholangiocarcinoma sign") in computed
      tomography].

PMID- 11570250
TI  - [Early detection of portal vein gas collections in ischemic colitis].

PMID- 11570251
TI  - [Small intestine invagination in metastatic intestinal malignant melanoma].

PMID- 11570252
TI  - [Intrahepatic splenosis].

PMID- 11570253
TI  - [Solitary adult lymphangioma of the liver as a very rare variant of benign space
      occupying lesion of the liver].

PMID- 11570254
TI  - Spanish doctors try switching therapy from month to month.

PMID- 11570255
TI  - German study finds whey protein supplement boosts antioxidants.

PMID- 11570256
TI  - Of power plants and energy shortages.

PMID- 11570257
TI  - High levels of lactic acid in some users of HAART.

PMID- 11570258
TI  - Autralian study links nukes, lactic acid to bone loss.

PMID- 11570259
TI  - Bone damage--more than just nukes involved.

PMID- 11570260
TI  - Drug-resistant HIV.

PMID- 11570261
TI  - Recent advances in the management and treatment of GI and hepatic diseases
      associated with HIV: Part 2.

PMID- 11570262
TI  - Study results presented on interferon/ribavirin combination therapy.

PMID- 11570263
TI  - Drug abuse health services funding available.

PMID- 11570264
TI  - HIV drug resistance Web site launched.

PMID- 11570265
TI  - HIV-1 non-B subtypes in clinical practice.

PMID- 11570266
TI  - Postexposure prophylaxis for HIV infection.
AB  - Postexposure prophylaxis (PEP) is routinely recommended following occupational
      exposure to HIV. Most PEP regimens involve the use of 2 nucleoside reverse
      transcriptase inhibitors with or without the addition of a protease inhibitor.
      PEP is also increasingly being prescribed following nonoccupational exposure to
      HIV. It is important that careful risk assessment be performed before prescribing
      PEP in both the occupational and nonoccupational settings and that risk reduction
      measures be emphasized.

PMID- 11570267
TI  - Primary effusion lymphoma with herpesvirus 8 DNA in patients coinfected with HIV
      and hepatitis C virus: a report of 2 cases.
AB  - The primary effusion lymphoma (PEL), commonly described in patients with AIDS, is
      a unique subset of diffuse large cell lymphoma in which the malignant lymphocytes
      proliferate exclusively in serous cavities. The cytologic, immunophenotypic, and
      molecular features of PEL are presented from findings of 2 patients coinfected
      with HIV and hepatitis C virus who presented with abdominal pain. Abdominal
      radiography in both patients displayed marked peritoneal effusions.
      Cytomorphologic examination of peritoneal fluid revealed a malignant lymphoma in
      both. Their immunophenotypic expression was CD30 (Ki-1) and epithelial membrane
      antigen. Molecular analysis demonstrated human herpesvirus 8 DNA in both patients
      and bcl-2 oncogene rearrangement within the major breakpoint region of t(14;18)
      chromosome translocation in Case B only. Clinical correlation supports the
      current concept that PEL represents a primary HIV/AIDS-related lymphoma in
      effusion. Cytomorphologic examination of body cavity fluid serves as a tool for
      the initial diagnosis of PEL.

PMID- 11570268
TI  - HIV and alcohol use: consequences of comorbidity.

PMID- 11570269
TI  - Systemic lupus erythematosus.

PMID- 11570270
TI  - Determination of lactic acid, pyruvic acid, and ketone bodies in serum and
      cerebrospinal fluid by HPLC.

PMID- 11570271
TI  - Quantitative real-time RT-PCR to study hepatitis C virus binding onto mammalian
      cells.

PMID- 11570272
TI  - Heparin therapy and monitoring: a role for the chromogenic antifactor Xa assay.

PMID- 11570273
TI  - Pharmacogenomics in the clinical laboratory.

PMID- 11570274
TI  - Biofilms of Candida albicans and their associated resistance to antifungal
      agents.

PMID- 11570275
TI  - [Introduction to the community meeting devoted to plant pathogenic agents:
      discovery, pathogenicity, problems for society].

PMID- 11570276
TI  - [Plant fungi: the first pathogenic agents recognized in the history of science].
AB  - The eighteenth century is the beginning of the scientific emergence of plant
      pathology. Naturalists disproved spontaneous generation, meteorological and
      supernatural origins of plant diseases. It is necessary to explain plant
      alterations and to find possibilities of control to reduce significant losses of
      yield and to limit famine. In 1728, the words 'plant parasite', 'plant disease',
      and 'epidemics' were used for the first time. In 1755, the first seed treatment
      and, in 1805 the first description of a whole cycle of plant disease were
      proposed. In the nineteenth century much work on bunt and rusts of wheat, potato
      downy mildew, and grape vine powdery mildew established the scientific status of
      plant pathology. A retrospective analysis of these early developments shows a
      very good concordance with Koch's postulate published one century later.

PMID- 11570277
TI  - [Plants and pathogenic agents, a refined and dangerous relationship: the example
      of fungi].
AB  - Plant-fungus interactions are highly diverse, either being beneficial to the host
      plant such as those leading to mycorhizal symbiosis, or very detrimental when
      leading to severe diseases. Since the beginning of agriculture, improvement of
      plant resistance to pathogens has remained a major challenge. Breeding for
      resistance, first conducted empirically in the past centuries, was then performed
      on a more theoretical basis after the statement of heredity laws by Mendel at the
      end of the XIXth century. As a result, most cultivated species contain various
      cultivars whose resistance or susceptibility to a given pathogen species depend
      on their interaction with various races of that pathogen. Such highly specific
      race-cultivar systems are particularly suited for understanding the molecular
      dialogue which underlies compatible (host susceptible/pathogen virulent) or
      incompatible (host resistant/pathogen avirulent) interactions. During the
      twentieth century, one of the major events that paved the way for future research
      was the statement by Flor [1946, 1947] of the gene-for-gene concept. Studying
      inheritance of the disease phenotype in the interaction between flax and
      Melampsora lini he showed that resistance in the host and avirulence in the
      pathogen are dictated by single dominant genes which correspond one to one, i.e.
      one resistance gene for one avirulence gene. The fact that incompatibility may
      depend on the presence of only one resistance (R) gene in the host and one
      avirulence (Avr) gene in the pathogen was fully confirmed about 40 years later.
      Molecular genetics and complementation experiments have allowed to isolate
      numerous R and Avr genes from various plant-pathogen systems, and to verify the
      gene-for-gene concept. These studies have enlightened the elicitor/receptor
      concept, formerly introduced to account for the specificity of the compatible and
      incompatible interactions. The present knowledge of R and Avr genes also allows
      to predict how such genes have evolved and how they could be used to improve
      disease resistance. At the beginning of the twenty first century, this remains a
      major challenge in view of the severe losses caused by pests and pathogens to
      most crops on the earth.

PMID- 11570278
TI  - [Discovery of phytopathogenic bacteria 100 years ago: transatlantic controversies
      and polemics].
AB  - The demonstration of a bacterial cause of some plant diseases has been claimed
      few years after it was commonly recognized that bacteria were able to cause
      diseases of human and animal. Nevertheless, some sharp controversies took place,
      between German and American specialists (1897-1901), before the existence of
      bacterial diseases of plants was accepted by all phytopathologists. Nowadays,
      about 350 bacteria are described, which infect plants: they are pathovars, or
      subspecies, belonging to 21 genera. Bacterial diseases of plants can be
      classified into three major categories according to the type of symptoms shown by
      the infected plant: necrosis and wilt, soft-rot, tumour. The interaction between
      bacteria and plant cells is usually established from the apoplast, although some
      bacteria are xylem or phloem limited. This interaction involves an original
      protein secretion system (which is also described in bacteria pathogenic for
      animals), hydrolytic enzymes (pectinases, cellulases), toxins and/or
      phytohormones. Bacteria of one group (Agrobacterium) modify the plant metabolism
      after gene transfer from a plasmid. On the economic and social point of view,
      these diseases may be limiting factors of some key-productions (rice, cassava).
      In addition, they play a role in reducing the quality of agricultural products
      (reduced growth, spots on leaves and fruits). Control of bacterial diseases is
      limited. It relies usually on a combination of prophylaxy, chemical applications,
      and use of resistant genotypes.

PMID- 11570279
TI  - [Current concepts on the pathogenicity of phytopathogenic bacteria].
AB  - What are the molecular determinants that make a bacterium a plant pathogen? In
      the last 10-20 years, important progress has been made in answering this
      question. In the early 20th century soon after the discovery of infectious
      diseases, the first studies of pathogenicity were undertaken. These early studies
      relied mostly on biochemistry and led to the discovery of several major
      pathogenicity determinants, such as toxins and hydrolytic enzymes which govern
      the production of major disease symptoms. From these pioneering studies, a
      simplistic view of pathogenicity arose. It was thought that only a few functions
      were sufficient to transform a bacterium into a pathogen. This view rapidly
      changed when modern techniques of molecular genetics were applied to analyse
      pathogenicity. Modern analyses of pathogenicity determinants took advantage of
      the relatively simple organization of the haploid genome of pathogenic bacteria.
      By creating non-pathogenic mutants, a large number of genes governing bacterium
      host interactions were identified. These genes are required either for host
      colonization or for the production of symptoms. Even though the role of motility
      and chemotaxis in these processes is still unclear, it is clear that a strong
      attachment of Agrobacterium to plant cells is a prerequisite for efficient plant
      transformation and disease. Other important pathogenicity factors identified with
      a molecular genetic approach include hydrolytic enzymes such as pectinases and
      cellulases which not only provide nutrients to the bacteria but also facilitate
      pathogen invasion into host tissues. The precise role of exopolysaccharide in
      pathogenicity is still under discussion, however it is has been established that
      it is crucial for the induction of wilt symptoms caused by Ralstonia
      solanacearum. Trafficking of effector proteins from the invading bacterium into
      the host cell emerged recently as a new central concept. In plant pathogenic
      bacteria, protein translocation takes place through the so-called 'type II
      secretion machinery' encoded by hrp genes in the bacterium. These genes are
      present in representatives of all the major groups of Gram negative plant
      pathogenic bacteria except Agrobacterium. Most of these genes have counterparts
      in pathogens of mammals (including those of human) and they also play a central
      role in pathogenicity. Additionally, recent evidence suggests that a 'type IV
      secretion machinery' injects bacterial proteins into host cells. This machinery,
      originally found to be involved in the transfer of t-DNA from Agrobacterium into
      plant cells, was recently shown to translocate pathogenicity proteins in
      pathogens of mammals such as Helicobacter pylori and Brucella. Discovery of the
      trafficking of proteins from the pathogen into host cells revolutionized our
      conception of pathogenicity. First, it rather unexpectedly established the
      conservation of basic pathogenicity strategies in plant and animal pathogens.
      Second, this discovery changes our ideas about the overall strategy (or
      mechanism) of pathogenicity, although we still think the end result is
      exploitation of host cell nutritive components. Rather than killing the host cell
      from outside, we envision a more subtle approach in which pathogens inject
      effector proteins into the host cell to effect a change in host cell biology
      advantageous to the pathogen. Identification of the effector proteins, of their
      function and of the corresponding molecular targets in the host is a new
      challenge which will contribute to the conception of new strategies to control
      diseases.

PMID- 11570280
TI  - Mycoplasmas, plants, insect vectors: a matrimonial triangle.
AB  - Plant pathogenic mycoplasmas were discovered by electron microscopy, in 1967,
      long after the discovery and culture in 1898 of the first pathogenic mycoplasma
      of animal origin, Mycoplasma mycoides. Mycoplasmas are Eubacteria of the class
      Mollicutes, a group of organisms phylogenetically related to Gram-positive
      bacteria. Their more characteristic features reside in the small size of their
      genomes, the low guanine (G) plus cytosine (C) content of their genomic DNA and
      the lack of a cell wall. Plant pathogenic mycoplasmas are responsible for several
      hundred diseases and belong to two groups: the phytoplasmas and the spiroplasmas.
      The phytoplasmas (previously called MLOs, for mycoplasma like organisms) were
      discovered first; they are pleiomorphic, and have so far resisted in vitro
      cultivation. Phytoplasmas represent the largest group of plant pathogenic
      Mollicutes. Only three plant pathogenic spiroplasmas are known today. Spiroplasma
      citri, the agent of citrus stubborn was discovered and cultured in 1970 and shown
      to be helical and motile. S. kunkelii is the causal agent of corn stunt. S.
      phoeniceum, responsible for periwinkle yellows, was discovered in Syria. There
      are many other spiroplasmas associated with insects and ticks. Plant pathogenic
      mycoplasmas are restricted to the phloem sieve tubes in which circulates the
      photosynthetically-enriched sap, the food for many phloem-feeding insects
      (aphids, leafhoppers, psyllids, etc.). Interestingly, phytopathogenic mycoplasmas
      are very specifically transmitted by leafhoppers or psyllid species. In this
      paper, the most recent knowledge on phytopathogenic mycoplasmas in relation with
      their insect and plant habitats is presented as well as the experiments carried
      out to control plant mycoplasma diseases, by expression of mycoplasma-directed
      antibodies in plants (plantibodies).

PMID- 11570281
TI  - [Discovery of the first virus, the tobacco mosaic virus: 1892 or 1898?].
AB  - Two scientists contributed to the discovery of the first virus, Tobacco mosaic
      virus. Ivanoski reported in 1892 that extracts from infected leaves were still
      infectious after filtration through a Chamberland filter-candle. Bacteria are
      retained by such filters, a new world was discovered: filterable pathogens.
      However, Ivanovski probably did not grasp the full meaning of his discovery.
      Beijerinck, in 1898, was the first to call 'virus', the incitant of the tobacco
      mosaic. He showed that the incitant was able to migrate in an agar gel, therefore
      being an infectious soluble agent, or a 'contagium vivum fluidum' and
      definitively not a 'contagium fixum' as would be a bacteria. Ivanovski and
      Beijerinck brought unequal but decisive and complementary contributions to the
      discovery of viruses. Since then, discoveries made on Tobacco mosaic virus have
      stood out as milestones of virology history.

PMID- 11570282
TI  - Plant viruses and the recent discovery of unforeseen basic cellular processes.
AB  - Given their small genome size, the biological cycle of plant viruses is tightly
      integrated with the cellular processes of their host plants, so that studies of
      the viral biology will often provide insights into basic cellular processes. In
      the last decade, two such unforeseen mechanisms were discovered. One concerns
      intercellular communications: for their movement in infected plants, viruses use
      channels (plasmodesmata, phloem) also used by the plant to exchange information
      rich molecules (proteins, RNAs) between cells. The second phenomenon concerns the
      existence, in plants, of an anti-viral defence mechanism based on the specific
      degradation of RNA molecules in the cytoplasm. This same mechanism, also allowing
      the regulation of gene expression (post-transcriptional gene silencing, PTGS) now
      appears to be widespread in pluricellular organisms. Besides their general
      interest, these new results modify drastically our vision of interactions between
      plant and viruses and raise numerous new research questions.

PMID- 11570283
TI  - A naked plant-specific RNA ten-fold smaller than the smallest known viral RNA:
      the viroid.
AB  - Viroids are subviral plant pathogens at the frontier of life. They are solely
      composed by a single-stranded circular RNA of 246-401 nt with a compact secondary
      structure. Viroids replicate autonomously when inoculated into their host plants
      and incite, in most of them, economically important diseases. In contrast to
      viruses, viroids do not code for any protein and depend on host enzymes for their
      replication, which in some viroids occurs in the nucleus and in others in the
      chloroplast, through a rolling-circle mechanism with three catalytic steps. Quite
      remarkably, however, one of the steps, cleavage of the oligomeric head-to-tail
      replicative intermediates to unit-length strands, is mediated in certain viroids
      by hammerhead ribozymes that can be formed by their strands of both polarities.
      Viroids induce disease by direct interaction with host factors, the nature of
      which is presently unknown. Some properties of viroids, particularly the presence
      of ribozymes, suggest that they might have appeared very early in evolution and
      could represent 'living fossils' of the precellular RNA world that presumably
      preceded our current world based on DNA and proteins.

PMID- 11570284
TI  - [Stimulation of plant natural defenses].
AB  - Some defense mechanisms of plants are of the passive type while others are
      induced after perception of the pathogenic microorganism (very specific gene-for
      gene recognition) or of microbial components (non specific elicitors). These
      recognition events trigger an array of plant signals and a cascade of signalling
      pathways which activate a battery of metabolic alterations responsible for the
      observed induced resistance. These include the stimulated production of low
      molecular weight molecules with antibiotic activity, cell wall reinforcement by
      deposition and cross-linking of various macromolecules, and accumulation of a
      wide range of PR ('pathogenesis-related') proteins that exhibit direct and/or
      indirect antimicrobial activities. The present studies aim to characterize
      natural elicitors or design chemical messengers capable of triggering an array of
      plant defense responses. Treatments of plants with elicitors could be an
      alternative strategy of crop protection with a more satisfactory preservation of
      the environment.

PMID- 11570285
TI  - Zinc and the immune system.

PMID- 11570286
TI  - Study examines link between low levels of zinc and survival.

PMID- 11570287
TI  - Can vitamin E help people recover from hepatitis B?

PMID- 11570288
TI  - Extra co-enzyme Q10 for statin-users?
AB  - Co-enzyme Q10, or ubiquinone, is a nutrient that is produced in small amounts by
      the body and is also obtained from food. It plays a key role in helping the body
      convert food into energy. Co-enzyme Q10 is also an important antioxidant, the
      need for which appears to increase during HIV infection and in people who use
      certain lipid-lowering drugs called statins.

PMID- 11570289
TI  - Background on glucose--from food to blood sugar.

PMID- 11570290
TI  - Indinavir--effect on sugar and insulin.

PMID- 11570291
TI  - Protease inhibitors and blood sugar problems.

PMID- 11570292
TI  - Moving stroke care forward.

PMID- 11570293
TI  - Why are we doing so little clinical research? Part 1: Clinical descriptive
      research.

PMID- 11570294
TI  - Increasing poverty threatens the health of all Canadians.

PMID- 11570295
TI  - Can herbal products be used safely during pregnancy? Focus on echinacea.
AB  - QUESTION: Many of my patients are now using herbal medicines; some even use them
      during pregnancy. As we enter the "cold and flu" season, many are inquiring about
      use of the herb echinacea to prevent these ailments. Is there any evidence to
      suggest that use of echinacea during pregnancy is safe? ANSWER: Although herbal
      products have been used in the past during pregnancy and delivery, there is
      little evidence showing they are safe. Many authoritative reviews of echinacea
      report that its safety for use during pregnancy has not been established. A
      recent Motherisk study showed that use of echinacea during the first trimester of
      pregnancy was not associated with increased risk of major malformations.

PMID- 11570296
TI  - Ophthaproblem. Myelinated retinal nerve fibre layer.

PMID- 11570297
TI  - Is a chaperone always necessary?

PMID- 11570298
TI  - Legionella pneumonia.

PMID- 11570299
TI  - Is kava extract effective for treating anxiety?

PMID- 11570300
TI  - Direct-to-consumer advertising. Finasteride for male pattern hair loss.

PMID- 11570301
TI  - Preventive health information on the Internet. Qualitative study of consumers'
      perspectives.
AB  - OBJECTIVE: To explore how best to make high-quality preventive health information
      available to consumers on the Internet. DESIGN: Focus groups. SETTING: Three
      urban workplaces and one local hospital with patients from a rural family medical
      practice. PARTICIPANTS: Twenty-two men and 17 women patients. METHOD: Qualitative
      survey of four focus groups, analysis of transcripts and researchers' notes. MAIN
      FINDINGS: Five themes characterized participants' perceptions of a consumer
      website of evidence-based preventive guidelines: content expectations, website
      design, trustworthiness of content, marketing, and the implications of consumer
      health information on the Internet. CONCLUSION: Consumers want preventive health
      information both for taking care of themselves and for participating in a more
      informed way in their health care when they see a physician. Findings of this
      study reveal some ways in which consumers' use of Internet health information can
      affect physicians' and other health professionals' work.

PMID- 11570302
TI  - [Regionalization of rehabilitation services. Survey of users of a Quebec center].
AB  - OBJECTIVE: To understand the situation of and difficulties encountered by users
      of a supraregional rehabilitation institute when they are transferred from the
      institute to facilities in their own regions, and to discover how they address
      these difficulties. DESIGN: Qualitative descriptive study. SETTING: Regions in
      Quebec served by a physical rehabilitation institute (Institut de readaptation en
      deficience physique de Quebec). PARTICIPANTS: Thirty-nine people who used
      services at the institute and then sought rehabilitation in their own regions.
      METHOD: Telephone survey using a validated questionnaire with both open-ended and
      closed questions. MAIN FINDINGS: About 69% of users had difficulty obtaining
      adequate follow up in their regions; the regions lacked professionals with
      expertise; more efficient methods of communication are required; and physicians'
      role in providing continuity of care needs to be recognized. CONCLUSION:
      Providing continuity of care on a regional basis is a formidable challenge for
      the entire health and social services network, but ways of meeting this challenge
      are within reach.

PMID- 11570303
TI  - Health care system reform. Ontario family physicians' reactions.
AB  - OBJECTIVE: To determine the effect on a cohort of family physicians of health
      care system reforms in Ontario and the relationship of reforms to their career
      satisfaction. DESIGN: Follow-up survey in 1999 of a cohort initially studied in
      1993, posing many of the original questions along with some new ones. Four focus
      groups of other Ontario family physicians. SETTING: Family practices in Ontario.
      PARTICIPANTS: All family physicians who had received certification after
      completing a family medicine residency between 1989 and 1991 and were practising
      in Ontario in 1993. This report addresses only those members of the cohort who
      continued to practise family medicine in Ontario (N = 236). Four focus groups
      with a total of 27 family physicians. MAIN OUTCOME MEASURES: Reaction to health
      care system reforms. Perceived effect of reforms on practice. Current perception
      of quality of health care system and level of career satisfaction and changes in
      these variables since 1993. RESULTS: Response rate was 53% of original cohort.
      Only three of 13 selected health reforms were believed to have had a favourable
      effect. Physicians reported lower levels of satisfaction with their careers.
      Overall quality of the health care system was perceived by both respondents and
      focus group members to have declined. Several difficulties affected practice and
      personal life. CONCLUSION: Family physicians viewed the effect of health care
      reforms negatively and were significantly less satisfied with their careers than
      they were in 1993. Better consultation with stakeholders before implementation of
      reforms is needed to ensure that these stakeholders understand the likely effects
      of these reforms.

PMID- 11570304
TI  - Current management of acute ischemic stroke. Part 1: Thrombolytics and the 3-hour
      window.
AB  - OBJECTIVE: To help family physicians who care for patients with acute stroke or
      who are involved in planning service delivery or resource allocation to
      understand recent developments in acute stroke care. QUALITY OF EVIDENCE: A
      MEDLINE search indicated that most data were derived from well designed,
      randomized, double-blind, placebo-controlled trials, including all the largest
      international studies and large systematic reviews. MAIN MESSAGE: Treatment of
      acute stroke with tissue plasminogen activator seems beneficial for certain
      patients with certain kinds of stroke. Because thrombolytic therapy is not
      without risk and requires substantial resources, it should be administered only
      by physicians trained in its use and in centres with the necessary experience and
      resources. Because time is important, an organized and efficient system of stroke
      care with collaboration between hospital and prehospital care providers and help
      from ordinary citizens is essential. CONCLUSION: Management of acute stroke is an
      emerging discipline; many potential therapies are still experimental.

PMID- 11570305
TI  - Current management of acute ischemic stroke. Part 2: Antithrombotics,
      neuroprotectives, and stroke units.
AB  - OBJECTIVE: To help family physicians who care for patients with acute stroke or
      who are involved in planning service delivery or resource allocation to
      understand recent developments in acute stroke care. QUALITY OF EVIDENCE: A
      MEDLINE search indicated that most data were derived from well designed,
      randomized, double-blind, placebo-controlled trials, including all the largest
      international studies and large systematic reviews. MAIN MESSAGE: Routine
      anticoagulation is not recommended except for circumstances such as cardioembolic
      stroke or deep vein thrombosis prophylaxis. Antiplatelet therapy with low-dose
      acetylsalicylic acid (or another antiplatelet agent if ASA is contraindicated)
      should be initiated within 48 hours of stroke onset, although benefit is modest.
      Dedicated care for stroke patients reduces morbidity and mortality and can be
      cost effective. Recent research into defibrinogenating and neuroprotective agents
      suggests some benefit, although none are currently licensed for use. Combination
      therapy might be the answer. CONCLUSION: Management of acute stroke is an
      emerging discipline; many potential therapies are still experimental.

PMID- 11570306
TI  - Alzheimer's disease. To tell or not to tell.
AB  - OBJECTIVE: To evaluate reasons for telling or not telling patients about a
      diagnosis of Alzheimer's disease and to assess the effect of such a decision on
      patients, families, physicians, and the health care system. QUALITY OF EVIDENCE:
      MEDLINE was searched from January 1966 to December 1999 using the key words
      "Alzheimer's disease" or "dementia" and "truth disclosure" or "attitude to
      health." There were no randomized controlled trials (level I evidence) in the
      literature. Articles identified provided level II evidence (case-controlled and
      cross-sectional studies) or level III evidence (expert opinion). All articles
      identified were chosen for this study. MAIN MESSAGE: In attempting to determine
      whether or not to communicate a diagnosis of Alzheimer's disease, physicians face
      a predicament: the desire to communicate honestly and directly with a patient is
      sometimes at variance with the equally compelling desire to concur with the
      patient's family's reluctance to disclose the diagnosis. Most Alzheimer's
      patients should be told of their diagnosis, but the timing of the discussion and
      the way it occurs are crucial to a good outcome. Most patients accept the
      information without a catastrophic response. Physicians must gain support from
      patients' families because it could take time for them to accept disclosure of
      what is perceived as a "hopeless" diagnosis. CONCLUSION: We must continue to
      support Alzheimer's patients and promote hope.

PMID- 11570307
TI  - Colorectal cancer screening. Recommendation statement from the Canadian task
      force on preventive health care.

PMID- 11570308
TI  - Residents' page. Family Medicine North: this is the life!

PMID- 11570309
TI  - Hypothesis: the research page. Grovel and sweat. Recruiting family doctors for
      research studies.

PMID- 11570311
TI  - Taking control of your appointment schedule. Part 2: Establishing expectations
      and scheduling with computers.

PMID- 11570310
TI  - [Staging of colorectal cancer. Official recommendations of the Canadian Study
      Group on Preventive Medicine].

PMID- 11570312
TI  - Controlled trial with a monthly combination injectable contraceptive in Europe.
AB  - In a controlled, multicenter trial conducted in Europe, the safety and efficacy
      of a monthly injectable combination hormone contraceptive were found to be
      comparable to those of an oral contraceptive. There were no contraceptive
      failures in either arm of the trial. The incidence and types of side-effects were
      similar. The rates of patient satisfaction in the monthly injectable and oral
      contraceptive arms of the study were also comparable; both exceeded 90%. The
      results from the European study are consistent with clinical trials conducted
      elsewhere and support the conclusion that the monthly combination injectable
      contraceptive represents a desirable new birth control method. Data from the 24
      week interim analyses are presented.

PMID- 11570314
TI  - Criteria for appropriate birth control.
AB  - Women seeking protection from pregnancy require adequate information about the
      relative merits and risks of current contraceptive options in order to make an
      informed choice. A basic understanding of mechanisms of action, the projected
      rates of efficacy, the demands on compliance, and the risks of side-effects
      permits women to weigh options appropriately and attain confidence in their
      chosen method. An informed woman is also in a better position to switch to
      alternative methods in the event of dissatisfaction or changing needs. Within the
      category of highly effective methods of birth control, to which a monthly
      combination injectable contraceptive has recently been added in several
      countries, there are important distinctions in relative reversibility, effect on
      menstrual cycle and confidentiality.

PMID- 11570313
TI  - Controlled trial with a monthly combination injectable contraceptive in the USA.
AB  - A monthly injectable contraceptive combining estradiol cypionate and
      medroxyprogesterone acetate was found to be well tolerated and effective in a
      phase III prospective, multicenter trial conducted in the United States. In this
      open-label comparison with an oral contraceptive, there were no pregnancies in
      the group receiving the monthly combination injectable contraceptive versus one
      pregnancy in those receiving the oral contraceptive. The rates of discontinuation
      for adverse events in the two treatment groups over the 60-week trial did not
      differ significantly. The majority of patients in both groups reported
      satisfaction with the method of contraception which they were receiving.

PMID- 11570315
TI  - A monthly combination injectable: a new contraceptive option. Introduction.

PMID- 11570316
TI  - Monthly combination injectable contraceptives.

PMID- 11570317
TI  - Clarification of terms.

PMID- 11570318
TI  - The North Carolina Cancer Control Program. Caring for uninsured and low-income
      patients with cancer.

PMID- 11570319
TI  - Cancer control legislation and policy milestones in North Carolina.

PMID- 11570320
TI  - Results from the 1999 North Carolina Youth Tobacco Survey. A call to action.

PMID- 11570321
TI  - Teen empowerment movement to prevent tobacco use by North Carolina's youth.
AB  - Strong youth and adult leadership and exemplary policy and program interventions
      put a unique synergy to work in North Carolina. The state aspires to be a model
      for the nation in overcoming barriers related to tobacco use prevention by
      empowering its greatest resource--youth. New grant funding is building the
      foundation for youth empowerment programs, and increased and sustained funding is
      being sought to significantly expand these efforts. Youth speak with a fresh
      voice, bringing energy and conviction, as well as non-traditional ideas and
      strategies to the achievement of their goals. By changing public opinion and
      influencing the actions of leaders in the nation's leading tobacco state, the
      North Carolina Tobacco Prevention and Control Branch will develop leadership for
      tobacco use prevention that will serve the entire nation.

PMID- 11570322
TI  - Labored breathing. Policies to eliminate environmental tobacco smoke exposure in
      North Carolina.

PMID- 11570323
TI  - Prostate cancer.

PMID- 11570324
TI  - Breast cancer.

PMID- 11570326
TI  - Cancer clinical trials.

PMID- 11570325
TI  - Cervical cancer and the Pap test.

PMID- 11570328
TI  - Prostate cancer as a public health issue in North Carolina.

PMID- 11570327
TI  - 'What do they know about it?' How the North Carolina public views cancer clinical
      trials: implications for primary care doctors.

PMID- 11570329
TI  - Colorectal cancer screening in North Carolina. Community clinicians'
      perspectives.

PMID- 11570330
TI  - Colorectal cancer in North Carolina. Risk factors, screening behaviors,
      incidence, stage at diagnosis, and mortality.

PMID- 11570331
TI  - Better Pap tests using liquid-based technology.

PMID- 11570332
TI  - Cancer control and the Central Cancer Registry of North Carolina.

PMID- 11570333
TI  - Re-framing risk: the changing context of disaster mitigation and preparedness.
AB  - This issue of Disasters explores the roles of NGOs and other actors in disaster
      mitigation and preparedness and also reviews broad international trends in risk
      management and disaster prevention. The need to address risk, and with that the
      motivation to improve disaster mitigation and preparedness, has tended to fall
      between the cracks of grander frameworks of development co-operation and
      humanitarian assistance. Despite the seemingly glaring need to reduce the
      horrific impact of floods, droughts and wars, disaster mitigation and
      preparedness have neither the allure of directly 'saving lives', nor of providing
      an 'escape from poverty'. There are, however, signs that risk management is
      becoming a mainstream concern. Factors such as the need to address factors that
      do not fit into traditional slots on the relief-development continuum, the rising
      economic costs of disasters and a growing acknowledgement that aid will never
      cover more than a small fraction of the costs of disasters are all leading to new
      approaches, priorities and institutional configurations. A realisation that
      dealing with risk and insecurity is a central part of how poor people develop
      their livelihood strategies has begun to position disaster mitigation and
      preparedness within many poverty alleviation agendas. A number of long-standing
      challenges remain; most of all, the complexities of maintaining the political
      will that is needed to ensure that risk management becomes more than a passing
      fad.

PMID- 11570334
TI  - NGO initiatives in risk reduction: an overview.
AB  - NGOs appear to be well placed to play a significant role in natural disaster
      mitigation and preparedness (DMP), working, as they do, with poorer and
      marginalised groups in society. However, there is little information on the scale
      or nature of NGO DMP activities. This paper reports the findings of a study
      seeking to address that gap. It confirms that NGOs are involved in a diverse
      range of DMP activities but that a number of them are not labelled as such.
      Moreover, evidence of the demonstrable quality and benefits of DMP involvement is
      poor. The paper concludes that a number of problems need to be overcome before
      DMP can be satisfactorily mainstreamed into NGO development and post-disaster
      rehabilitation programmes. However, there are some early indications of momentum
      for change.

PMID- 11570335
TI  - Disaster mitigation and preparedness: the case of NGOs in the Philippines.
AB  - The Philippines is very vulnerable to natural disasters because of its natural
      setting, as well as its socio-economic, political and environmental context-
      especially its widespread poverty. The Philippines has a well-established
      institutional and legal framework for disaster management, including built-in
      mechanisms for participation of the people and NGOs in decision-making and
      programme implementation. The nature and extent of collaboration with government
      in disaster preparedness and mitigation issues varies greatly according to their
      roots, either in past confrontation and political struggles or traditional
      charity activities. The growing NGO involvement in disaster management has been
      influenced by this history. Some agencies work well with local government and
      there is an increasing trend for collaborative work in disaster mitigation and
      preparedness. Some NGOs, however, retain critical positions. These organisations
      tend to engage more in advocacy and legal support for communities facing
      increased risk because of development projects and environmental destruction.
      Entry points into disaster mitigation and preparedness vary as well. Development
      oriented agencies are drawn into these issues when the community members with
      whom they work face disaster. Relief organisations, too, realise the need for
      community mobilisation, and are thus drawn towards development roles.

PMID- 11570336
TI  - The changing emphasis of disasters in Bangladesh NGOs.
AB  - Bangladesh is one of the most disaster-prone countries in the world, affected by
      cyclones and floods, as well as chronic hazards such as arsenic poisoning. NGOs
      have played a major role in bringing concerns related to risk management on to
      the national agenda and promoting a shift of focus from mere relief response to
      disaster mitigation and preparedness. The government has, after earlier
      scepticism, now accepted NGOs as major partners in these tasks. Innovative
      approaches, such as the use of microfinance, have been applied; many of which are
      related to preserving the gains of development efforts as part of rehabilitation.
      NGOs have pressured for better coordination with government. Improved structures
      are now approved, but it is still too early to judge their impact. Despite
      progress, neither NGOs nor governmental agencies have clearly defined roles in
      the effort to link disaster management priorities. This will ensure that longer
      term development efforts build on local capacities and reduce vulnerabilities.

PMID- 11570337
TI  - Disaster mitigation and preparedness on the Nicaraguan post-Mitch agenda.
AB  - Nicaragua provides an example of how a major disaster, in this case Hurricane
      Mitch, can transform the national agenda for disaster mitigation and
      preparedness. Hurricane Mitch was a reminder of how extremely disaster prone
      Nicaragua is, and also how neoliberal reforms have weakened governmental response
      capacity. In the face of critiques of how governmental policies had affected
      preparedness and response, discussions of this transformation became a highly
      politicised process where the debate over alternative development models tended
      to overshadow the original calls to strengthen risk management. Progress can be
      seen in some areas, such as disaster mitigation through environmental management.
      This study of NGO roles, and their relations with other key actors, draws
      attention to the need to anchor improved risk management in local-level NGO
      government collaboration. Structures are being put into place to achieve this
      aim, but dependence on donor financing raises questions regarding the longer-term
      sustainability of these efforts.

PMID- 11570338
TI  - Risk and the neoliberal state: why post-Mitch lessons didn't reduce El Salvador's
      earthquake losses.
AB  - Although El Salvador suffered light losses from Hurricane Mitch in 1998, it
      benefited from the increased international aid and encouragement for advance
      planning, especially mitigation and prevention interventions. Thus, one would
      have supposed, El Salvador would have been in a very advantageous position, able
      more easily than its economically crippled neighbours, Honduras and Nicaragua, to
      implement the 'lessons of Mitch'. A review of the recovery plan tabled by the El
      Salvador government following the earthquakes of early 2001 shows that despite
      the rhetoric in favour of 'learning the lessons of Mitch', very little mitigation
      and prevention had actually been put in place between the hurricane (1998) and
      the earthquakes (2001). The recovery plan is analysed in terms of the degree to
      which it deals with root causes of disaster vulnerability, namely, the economic
      and political marginality of much of the population and environmental
      degradation. An explanation for the failure to implement mitigation and
      preventive actions is traced to the adherence by the government of El Salvador to
      an extreme form of neoliberal, free market ideology, and the deep fissures and
      mistrust in a country that follow a long and bloody civil war.

PMID- 11570339
TI  - Interview with Michael W. Azzara, FACHE, president and CEO, Valley Health System.
      Interview by Kyle L. Grazier.

PMID- 11570340
TI  - Reviving staff spirit: a key to impressive service.

PMID- 11570341
TI  - Competing in a "consumer choice" market.

PMID- 11570342
TI  - Suddenly out of the field, Part I: The story.

PMID- 11570343
TI  - The struggle for equality in healthcare continues.
AB  - All healthcare providers, both institutional and individual, must make every
      effort to ensure that every person who seeks their medical care is offered
      competent, sincere, and equal treatment options. Unfortunately, this ideal
      scenario does not take into account the lack of diversity among care providers
      and the lack of culturally competent policies within healthcare delivery
      settings. As a result, many care providers continue to follow racially biased
      treatment practices and many organizations continue to ignore their public trust
      of providing fair treatment to everyone, regardless of skin color, gender,
      economic capabilities, etc. Although developing and implementing a diversity plan
      and culturally competent policies is very complex practically, politically, and
      programmatically for traditional institutional care providers, it must be done.
      The key ingredient to this effort is the absolute commitment and support of the
      organization's governing bodies and executive management. Institutions can
      certainly volunteer and begin to develop such programs that foster recruitment,
      selection, and retention of culturally competent care providers to ensure that
      equal healthcare is received by their patient populations. However, many
      institutions are already besieged by too many healthcare challenges to volunteer
      for such an effort. The Joint Commission on Accreditation of Healthcare
      Organizations and the National Council of Quality Assurance can certainly help
      jumpstart this effort by establishing an accreditation standard that requires all
      healthcare providers to establish and practice culturally competent care within
      their organizations. Providers must also embrace the diversity that is a part of
      our society and must not let race or ethnicity be a determining factor in
      offering treatment options.

PMID- 11570344
TI  - Hospital marketing orientation and managed care processes: are they coordinated?
AB  - The hospital marketing function has been widely adopted as a way to learn about
      markets, attract sufficient resources, develop appropriate services, and
      communicate the availability of such goods to those who may be able to purchase
      such services. The structure, tasks, and effectiveness of the marketing function
      have been the subject of increased inquiry by researchers and practitioners
      alike. A specific understanding of hospital marketing in a growing managed care
      environment and the relationship between marketing and managed care processes in
      hospitals is a growing concern. Using Kotler and Clarke's framework for assessing
      marketing orientation, we examined the marketing orientation of hospitals in a
      single state at two points in time--1993 and 1999. Study findings show that the
      overall marketing orientation score decreased from 1993 to 1999 for the
      respondent hospitals. The five elements of the Kotler and Clarke definition of
      marketing orientation remained relatively stable, with slightly lower scores
      related to customer philosophy. In addition, we evaluated the degree to which
      selected managed care activities are carried out as part of its marketing
      function. A significant (p < .05) decrease in managed care processes coordinated
      with the formal marketing function was evident from 1993 to 1999. With increasing
      numbers of managed care plan enrollees, hospitals are likely focusing on
      organizational buyers as important customers. In order to appeal to
      organizational buyers, hospital executives may be focusing more on clinical
      quality and cost efficiency in the production of services, which will improve a
      hospital's position with organizational buyers.

PMID- 11570345
TI  - Planned improvement of the cardiology patient placement process.

PMID- 11570346
TI  - Facility profile. Modular construction brings facility up to speed.

PMID- 11570347
TI  - Clean and green. H2E program helps facilities improve their environmental
      performance.

PMID- 11570348
TI  - Shocking truth! Important advice on preventing electrical hazards in hospitals.

PMID- 11570349
TI  - Art for health's sake. A step-by-step approach to developing a facility arts
      program.

PMID- 11570350
TI  - Safety first. JCAHO's new patient safety standards to affect environment of care.

PMID- 11570351
TI  - Carpeting course. Tips for selecting and maintaining carpets in health
      facilities.

PMID- 11570352
TI  - Patients will be in driver's seat as plans seek next generation of savings.

PMID- 11570353
TI  - Personal freedom called key to coverage.

PMID- 11570354
TI  - The battle over full-body scans.

PMID- 11570355
TI  - Memoranda of understanding between Medicaid MCOs and public health departments.
AB  - PURPOSE: This evaluation research project was conducted to describe local
      perspectives on creating and implementing mandated memoranda of understanding
      (MOU) between Medicaid managed care organizations and local health departments
      (LHD), to provide insights into the strengths and limitations of MOU, and to
      share information on their use as tools for interorganizational service
      coordination. DESIGN AND METHODOLOGY: A cross-sectional, qualitative and
      quantitative, self-administered, mailback survey was conducted with employees of
      MCOs and LHDs in California having experience in creating and/or implementing
      state-mandated MOU in nine service areas. Descriptive and qualitative results are
      reported. PRINCIPAL FINDINGS: The creation of MOU was facilitated by supportive
      leadership, previous collaborative experience, and the state mandate. The
      majority of respondents believed the MOU worked well to achieve coordination of
      services. MOU strengths and limitations were identified. The MOU were reported to
      have contributed to an increase in participation in four of six types of
      collaborative activities. Perceived quality of health care services for Medicaid
      participants improved with the MOU, but no impact on quality of public health
      services was reported. A majority (78 percent) supported a continuation of the
      mandated policy. Some organizations reported expanding the use of MOU beyond
      mandated areas. CONCLUSIONS: Study respondents held generally positive
      perceptions of the strengths of MOU and supported continuation of the mandated
      MOU policy in California. Their experience demonstrates a capacity for MCOs and
      LHDs to work together on health care coordination issues despite the difficulties
      inherent in interorganizational collaboration.

PMID- 11570356
TI  - Minnesota buyers coalition back on feet, plans expansion.

PMID- 11570357
TI  - 'Prevention doesn't pay?' Logic explodes this myth.

PMID- 11570358
TI  - Proceedings of the 30th annual meeting of the Society for Computers in
      Psychology. New Orleans, Louisiana, USA. November 16, 2000.

PMID- 11570359
TI  - Supply of physicians' services in Ontario.

PMID- 11570360
TI  - Biopersistence, fiber length, and cancer risk assessment for inhaled fibers.
AB  - We briefly review the evidence that the carcinogenic risk posed by inhaled fibers
      depends principally on the lung burden of long fibers. We use a deposition
      clearance model to generate time-dependent lung burdens in rats of a dozen long
      fibers for various exposure concentrations. Together with a previously estimated
      potency factor for long fibers, we use the generated lung burdens to estimate
      risks of lung cancer associated with inhaled fibers in rats. Over a broad range
      of exposure concentrations, excess risk is a linear function of exposure
      concentration. Excess risk of lung cancer is also a linear function of weighted
      half-life for fibers for which the weighted half-life is short compared to the
      life span of the rat. We propose an approach to estimating human lung cancer risk
      associated with inhaled fibers from animal studies.

PMID- 11570361
TI  - Comment on: The effect of waiting for radiotherapy for grade III/IV gliomas.

PMID- 11570362
TI  - Has the outlook improved for amifostine as a clinical radioprotector.

PMID- 11570363
TI  - A population-based study of the incidence of Mullerian aplasia in Finland.

PMID- 11570364
TI  - "You'll know it when you see it" statistics.

PMID- 11570365
TI  - "You'll know it when you see it" statistics.

PMID- 11570366
TI  - Causation--or the great western cowboy "random chance" at work?

PMID- 11570367
TI  - "In silico experiments"--yes, but the great western cowboy "random chance" is
      still alive.

PMID- 11570369
TI  - "In silico experiments"--yes, but the great western cowboy "random chance" is
      still alive.

PMID- 11570368
TI  - "In silico experiments"--yes, but the great western cowboy "random chance" is
      still alive.

PMID- 11570370
TI  - Effect of conjugated estrogens on free IGF-I?

PMID- 11570371
TI  - Attachment of "menstrual" endometrium to peritoneum?

PMID- 11570372
TI  - Nunatak survival, tabula rasa and the influence of the Pleistocene ice-ages on
      plant evolution in mountain areas.

PMID- 11570373
TI  - Plant response to bruchins.

PMID- 11570374
TI  - Breaking glass?
AB  - "The Glass Ceiling for Women in the Life Sciences Meeting", organized by the
      European Molecular Biology Organization (EMBO), was held on 22-23 June 2001 in
      Heidelberg, Germany.

PMID- 11570375
TI  - Signaling at zero G: a comment.

PMID- 11570376
TI  - Clinical research:  the power of the nurse.

PMID- 11570377
TI  - Abstracts of the 3rd European Cytogenetics Conference. Paris, France, July 7-10,
      2001.

PMID- 11570379
TI  - British Association for Psychopharmacology summer meeting. 22-25 July 2001,
      Harrogate, United Kingdom. Abstracts.

PMID- 11570378
TI  - [The 31st Western/Eastern Regional Meeting of the Japanese Society of Nephrology.
      Abstracts].

PMID- 11570380
TI  - Improved right heart function with a compliant inflow artificial lung in series
      with the pulmonary circulation.
AB  - BACKGROUND: We previously reported a 50% incidence of immediate right heart
      failure using a rigidly housed, noncompliant inflow artificial lung in series
      with the pulmonary circulation in a healthy ovine survival model. Three device
      modifications resulted: (1) an inflow cannula compliance chamber, (2) an inlet
      blood flow separator, and (3) modification of the artificial lung outlet
      geometry, all to reduce resistance and mimic the compliance of the pulmonary
      vascular bed. METHODS: In 7 sheep, arterial grafts were anastomosed end-to-side
      to the proximal and distal main pulmonary artery, with the paracorporeal
      artificial lung interposed. A pulmonary artery snare between anastomoses diverted
      full pulmonary blood flow through the artificial lung for up to 72 hours.
      RESULTS: Six of 7 sheep exhibited good cardiac function throughout the test
      period: mean central venous pressure was 6.8 mm Hg (range, 4 to 11 mm Hg), mean
      cardiac output, 4.17 +/- 0.12 L/min (range, 2.4 to 6.3 L/min); before and after
      device mean pulmonary arterial pressure, 21.8 and 18.5 mm Hg, and left atrial
      pressure, 10.8 mm Hg. CONCLUSIONS: This modified artificial lung prototype with
      an inflow compliance chamber, blood flow separator, and modified outlet geometry
      has greatly improved cardiac function and initial survival in our healthy ovine
      model.

PMID- 11570382
TI  - The 5th annual scientific meeting of the Heart Failure Society of America.
      September 9-12, 2001. Abstracts.

PMID- 11570381
TI  - Saline-irrigated, cooled-tip radiofrequency ablation is an effective technique to
      perform the maze procedure.
AB  - BACKGROUND: We evaluated the effectiveness of the saline-irrigated-cooled-tip
      radiofrequency ablation (SICTRA) to produce linear intraatrial lesions. METHODS:
      Thirty patients with chronic atrial fibrillation and mitral valve disease were
      consecutively randomized to have mitral valve operation either with a Maze
      procedure (group A) or without (group B). Intraatrial linear lesions were made
      with an SICTRA catheter (20 to 32 W; 200 to 320 mL/h saline). An echocardiography
      and 24-hour electrocardiogram were obtained 12 months postoperatively. RESULTS:
      The cumulative frequencies of sinus rhythm in group A and B were 0.80 and 0.27 (p
      < 0.01). Restored biatrial contraction was present in 66.7% (6 of 9) of the group
      A patients in sinus rhythm. One patient from each group received a permanent
      pacemaker because of bradycardia. A fatal renal bleeding and mediastinitis
      occurred in 2 group A patients, 6 weeks postoperatively. One group A patient had
      sudden cardiac death at home, 4 months after operation. One patient from each
      group had lethal respiratory failure, 7 and 10 months after operation. Survival
      after 12 months for group A and B was 73% and 93% (p = 0.131). CONCLUSIONS: The
      SICTRA appeared to be an effective technique to perform the Maze procedure.

PMID- 11570383
TI  - What is your diagnosis? Atrioventricular septal defect.

PMID- 11570384
TI  - Bridging the divide: spinal cord repair by cellular transplantation--from
      research laboratory to therapeutic application.
AB  - Spinal cord injury remains a clinical problem for which new therapeutic options
      are required. Recent developments in spinal cord injury research have suggested
      that promotion of axonal regeneration by cellular transplantation may be a
      feasible future treatment modality and it is possible that small animal clinical
      patients may be the first to benefit from these new approaches. This article
      describes the experiments which have generated this optimism and considers the
      steps that will be required to make the transition from laboratory experiments to
      clinical application.

PMID- 11570385
TI  - Effects of feeding regimens on bodyweight, composition and condition score in
      cats following ovariohysterectomy.
AB  - The effects of ovariohysterectomy on bodyweight, composition and condition score
      were evaluated in 49 cats that were fed ad libitum and 11 cats that had their
      food allowances controlled with the aim of maintaining a stable bodyweight. In
      cats fed ad libitum, bodyweight increased by an average of 31 per cent in the 12
      months following ovariohysterectomy compared with 3.1 per cent over the 12 months
      before surgery, and this was largely due to increased body fat content. There was
      no difference in weight gain between cats fed dry or canned foods, but weight
      gain was inversely related to age and bodyweight at the time of neutering. Mean
      bodyweight increased by 7.5 per cent in the controlled feeding group, compared
      with 3.6 per cent over the 12 months before surgery, and individual bodyweights
      were maintained to within 10 per cent of pre-neutering values in nine cats. The
      other two cats experienced substantial weight gain (+20 per cent and +36 per
      cent), despite being fed only 40 kcal/kg/day. There were no significant changes
      in body composition of cats with controlled dietary allowances and their
      condition scores were significantly lower than those of cats fed ad libitum. The
      results confirm a link between ovariohysterectomy and the development of obesity
      in cats with free access to food, and indicate that substantial reductions in
      energy intake are required to prevent weight gain in such cats.

PMID- 11570386
TI  - Prevalence of odontoclastic resorptive lesions in a population of clinically
      healthy cats.
AB  - The prevalence of odontoclastic resorptive lesions (ORLs) was determined in a
      clinically healthy cat population (228 cats) using both clinical (oral
      examination) and radiographic (full-mouth series with intraorally positioned
      dental film) methods. The overall prevalence rate was 29 per cent (mean age of
      the cat population 4.9 years). The mandibular third premolars (307, 407) were the
      most commonly affected tooth and the pattern of ORL development was symmetrical
      in most cats. The risk of having ORLs was found to increase with increasing age
      and cats with clinically and radiographically missing teeth were more likely to
      have the condition. Neutering, gender, age at neutering or mean whole mouth
      gingivitis index did not affect the prevalence of ORLs.

PMID- 11570387
TI  - Effects of medetomidine and buprenorphine administered for sedation in dogs.
AB  - Medetomidine at doses of 10, 20 or 30 microg/kg was administered along with 10
      microg/kg buprenorphine intramuscularly to 48 dogs requiring sedation for various
      diagnostic or therapeutic procedures. The heart rate, respiratory rate and degree
      of sedation were recorded before and 30 minutes after administration of the
      drugs. Heart rate fell by a mean of 55 per cent and respiratory rate by a mean of
      62 per cent. Mean sedation scores were increased in all groups. Administration of
      atipamezole at the end of the period of sedation produced rapid recoveries, with
      a mean time to standing of 12 minutes. Animals that were anaesthetised required
      much less thiopentone than the 10 mg/kg recommended after premedication with
      acepromazine maleate.

PMID- 11570388
TI  - Gross pulmonary thrombosis in a greyhound.
AB  - A two-year-old greyhound was presented with progressive dyspnoea. Radiography
      showed a hypovascular lung pattern with hyperlucent lung fields and
      echocardiography revealed a large thrombus in the main pulmonary artery. Blood
      results showed azotaemia and marked hypoalbuminaemia. The dog's clinical
      condition continued to deteriorate and it was euthanased. Postmortem examination
      confirmed the presence of the pulmonary thrombus and revealed idiopathic
      membranous glomerulonephritis.

PMID- 11570389
TI  - Multilobular tumour of bone with no abnormalities on plain radiography in a dog.
AB  - A seven-year-old neutered female golden retriever was presented for an acute
      onset of cervical pain and ataxia. Intervertebral disc disease or neoplasia was
      suspected. There was no evidence of a soft tissue or bony mass on physical
      examination or survey radiographs. Cerebrospinal fluid analysis did not show any
      evidence of a neoplastic process. Myelographic evaluation identified an
      extradural mass lesion extending from inside the calvarium to the mid-body of the
      first cervical vertebra. No additional diagnostic tests were performed as the
      owners elected for euthanasia because of the high possibility of a neoplastic
      process with an accompanying poor prognosis. Multilobular tumour of bone was
      diagnosed on postmortem examination.

PMID- 11570390
TI  - Extraskeletal fibroblastic osteosarcoma in a rabbit (Oryctolagus cuniculus).
AB  - A seven-year-old rabbit was presented with a non-painful mass in the right upper
      lip. Tissue samples from the mass at three different stages of the disease
      process were diagnosed sequentially as an osteogenic sarcoma, a fibroblastic
      tumour with rudimentary osteoid formation and, lastly, a fibrosarcoma. No bone
      involvement or metastatic disease was found. The final diagnosis was of an
      extraskeletal fibroblastic osteosarcoma, which is, to the authors' knowledge, the
      first reported such case in a domestic rabbit. Without the first two tissue
      samples, an incorrect diagnosis would have been reached; therefore, this disease
      may be underrepresented in the literature.

PMID- 11570391
TI  - Radiography and ultrasonography in the diagnosis and treatment of abdominal
      enlargements in five guinea pigs.
AB  - Five guinea pigs with palpable abdominal masses were examined by radiography and
      ultrasonography, and laparotomy was performed. Splenic haematoma, splenic and
      uterine haemangioma, uterine fibroma and ovarian teratoma were found on
      histological examination after excision of the relevant organs. Both of the
      imaging methods allowed localisation of the affected organs, but the inner
      structure of the masses could only be imaged by ultrasonography. Ultrasonography
      served as an aid in decision-making with respect to the laparotomy. Surgery was
      successful in four out of the five cases. Both imaging methods were found to be
      useful in diagnosis and in determining the choice of treatment in cases of
      abdominal masses in guinea pigs.

PMID- 11570392
TI  - Looking at the heart of America.

PMID- 11570393
TI  - Animal cruelty and child abuse: investigating the link.

PMID- 11570394
TI  - Hepatitis C practice routines among Connecticut's naturopathic physicians.

PMID- 11570395
TI  - References to contemporary papers on acoustics.

PMID- 11570396
TI  - Update to reference 1 of Kessenich, CR. Osteoporosis and African-American women.
      Women's Health Issues 2000;10:300-4.

PMID- 11570397
TI  - Aedes aegypti lipophorin.
AB  - The purified lipophorin of Aedes aegypti (Diptera) is composed of two
      apolipoproteins: apolipophorin I (M(r)=224,000) and apolipophorin II
      (M(r)=73,000). The density of lipophorin is constant during the Aedes life-cycle
      and equal to 1.11 +/- 0.01 g/ml. The amount of lipophorin per animal, during the
      gonotrophic cycles, increases until 48 hr after blood-feeding and then decreases
      until there is a new blood intake. The density values and quantification of
      lipophorin during Aedes aegypti gonotrophic cycle suggest that the adaptation to
      a higher lipid transport demand during oogenesis in Aedes aegypti is accomplished
      by increasing the amount of lipophorin in the hemolymph. This response is
      different from that observed in Musca domestica (Diptera) that does not involve
      changes in hemolymph lipophorin levels.

PMID- 11570398
TI  - Deep-vein thrombosis in long-haul flights.

PMID- 11570399
TI  - Deep-vein thrombosis in long-haul flights.

PMID- 11570400
TI  - Deep-vein thrombosis in long-haul flights.

PMID- 11570401
TI  - Deep-vein thrombosis in long-haul flights.

PMID- 11570402
TI  - Deep-vein thrombosis in long-haul flights.

PMID- 11570403
TI  - Ethical study design.

PMID- 11570404
TI  - Frequency of protein Z deficiency in patients with ischaemic stroke.

PMID- 11570405
TI  - Trends in testicular cancer.

PMID- 11570406
TI  - Hyperkalaemia and apple juice.

PMID- 11570407
TI  - Hyperkalaemia and apple juice.

PMID- 11570408
TI  - Sex and gender matter.

PMID- 11570409
TI  - Behavioural problems in children with low birthweight.

PMID- 11570410
TI  - Tubal ligation and risk of ovarian cancer.

PMID- 11570411
TI  - Tubal ligation and risk of ovarian cancer.

PMID- 11570412
TI  - Refugees.

PMID- 11570413
TI  - Refugees.

PMID- 11570414
TI  - Tackling the diseases of poverty.

PMID- 11570415
TI  - Attempted nail-gun suicide: fluid management in penetrating cardiac injury.

PMID- 11570416
TI  - Adequate analgesia is a basic patient right.

PMID- 11570417
TI  - Polymer stereochemistry: an opportunity and a challenge on Titan.
AB  - It is suggested here that an alternative strategy for detecting signs of
      prebiotic chemistry on Titan would be to search for stereoregular polymers.
      Laboratory simulations of Titan's atmosphere suggest several interesting reactive
      vinyl monomers, including acrylonitrile. Polyacrylonitrile and derivatives made
      by side chain modification would be very interesting structures that could be
      envisioned as progenitors of complex chemical systems. The issues and challenges
      of considering polymer, rather than small molecule, stereochemistry as an
      indicator of prebiotic chemistry on Titan are briefly discussed.

PMID- 11570418
TI  - Miniaturization of enantioselective gas chromatography.
AB  - In the context of the Titan Chiral Organics Explorer (TCOE) mission, the
      theoretical and practical aspects of the miniaturization of enantioselective gas
      chromatography are discussed. The use of short columns (0.5-10 m) with a
      conventional inside diameter of 250 microm is proposed. The inside diameter
      should be increased for vacuum-assisted GC-MS using a restrictor at the inlet of
      the capillary. The feasibility of cryogenic enantioselective gas chromatography
      is demonstrated. The hitherto elusive use of chiral mobile phase additives in
      enantioselective gas chromatography is proposed.

PMID- 11570419
TI  - Search for extraterrestrial enantioenrichment by using chemical microsensors.
AB  - The use of enantioselective chemical microsensors is proposed for the search of
      extraterrestrial homochirality in space. The already established enantiomer
      discrimination-capability of chemical sensors and the feasibility of
      quantitatively determining the enantiomeric composition of a target analyte are
      demonstrated. The benefits of applying modern microsensor technology are
      presented followed by some concepts and scenarios including how chemical
      microsensors could be used in space.

PMID- 11570420
TI  - Electrochemical detectors: functional group analysis.
AB  - In addition to chromatographic resolution of enantiomeric compounds,
      electrochemical detection may be used to delineate structure. This information
      can be obtained via voltammetric measurement at various electrode materials. This
      paper focuses on isolated electrode arrays as used for the resolution of redox
      active compounds in liquid chromatography. For polar aliphatic compounds,
      electrocatalytic detection at noble metals using pulsed voltammetric detection
      can be used to identify certain functional groups (e.g., aldehydes, alcohols,
      amines, and thiols). Electrochemical systems are also versatile, rugged, and
      highly amenable to miniaturization, which are all important factors for
      consideration for inclusion in extraterrestrial exploration vehicles.

PMID- 11570421
TI  - Antibodies as chiral selectors for the determination of enantioenrichment.
AB  - Stereoselective antibodies are excellent chiral selectors for the routine
      analysis of enantiopurity in, e.g., enzyme-linked immunosorbent assays and
      immunosensors. Here, we describe the application of stereoselective, group
      specific antibodies to alpha-amino acids as tailor-made chiral selectors. The
      feasibility of chiral immunosensor techniques in space missions using these or
      other, newly designed antibodies is discussed.

PMID- 11570422
TI  - Low power, lightweight vapor sensing using arrays of conducting polymer composite
      chemically-sensitive resistors.
AB  - Arrays of broadly responsive vapor detectors can be used to detect, identify, and
      quantify vapors and vapor mixtures. One implementation of this strategy involves
      the use of arrays of chemically-sensitive resistors made from conducting polymer
      composites. Sorption of an analyte into the polymer composite detector leads to
      swelling of the film material. The swelling is in turn transduced into a change
      in electrical resistance because the detector films consist of polymers filled
      with conducting particles such as carbon black. The differential sorption, and
      thus differential swelling, of an analyte into each polymer composite in the
      array produces a unique pattern for each different analyte of interest, Pattern
      recognition algorithms are then used to analyze the multivariate data arising
      from the responses of such a detector array. Chiral detector films can provide
      differential detection of the presence of certain chiral organic vapor analytes.
      Aspects of the spaceflight qualification and deployment of such a detector array,
      along with its performance for certain analytes of interest in manned life
      support applications, are reviewed and summarized in this article.

PMID- 11570423
TI  - Doped nematic phases: a tool for amplifying and detecting chirality.
AB  - Doping nematic liquid crystals with non-racemic chiral compounds induces twisted
      nematics (cholesteric phases). This phenomenon allows the detection via
      spectroscopic or non-spectroscopic methods of chiral compounds through the
      detection (and eventually quantification) of the macroscopic induced cholesteric
      twist.

PMID- 11570424
TI  - Prospects for circular dichroism detection of nonracemic extraterrestrial organic
      molecules.
AB  - The use of circular dichroism is examined as a probe for the detection of
      nonracemic analytes on spacecraft explorations such as a planned mission to
      Titan. Advances in both instrument design and chemistry will be required to make
      such a method practicable. The focus of this paper is on chemical agents able to
      amplify the circular dichroism signal, which would simplify instrument problems
      and increase sensitivity. A classic phenomenon known as the Pfeiffer effect
      provides a conceptual strategy to achieve the necessary aims for chirality
      detection. Recent examples of Pfeiffer-related phenomena are discussed.

PMID- 11570425
TI  - Application of asymmetric autocatalysis to the determination of absolute
      configurations of amino acids with low enantiomeric excesses.
AB  - A method is proposed for the determination of the absolute configuration of amino
      acids with low enantiomeric excesses by using asymmetric autocatalysis of
      pyrimidyl alkanol with amplification of enantiomeric excess.

PMID- 11570426
TI  - Interconversion of chiral molecules in interstellar space.

PMID- 11570427
TI  - Challenges and approaches to the robotic detection of enantioenrichment on
      Saturn's moon, Titan.
AB  - Saturn's moon, Titan, is one of the most interesting locations for organic
      chemistry in the solar system. As a possible follow up to the Cassini-Huygens
      mission, which will conduct the first in situ analysis of the Titan atmosphere in
      2004, studies are underway for missions to explore in detail the chemical
      composition of Titan's atmosphere, surface, and oceans. In order to seek out and
      explore complex chemical systems that may represent steps on the pathway to life,
      instruments for detection of enantioenrichment should be included on such a
      mission. The formidable challenges of robotic measurement of enantioenrichment on
      Titan are summarized, and experimental approaches to this problem are reviewed.
      In addition, some speculations are offered concerning locations on Titan where
      complex fractionation of organic materials may have occurred.

PMID- 11570428
TI  - Geologic settings for aqueous organic synthesis on Titan revisited.
AB  - The photochemistry in Titan's cold reducing atmosphere is an evolutionary dead
      end. However, the hydrocarbons and nitriles deposited from the atmosphere can
      undergo aqueous synthesis into prebiotic molecules in ephemeral settings such as
      impact melt sheets. We re-examine the longevity of aqueous solutions on Titan,
      noting that recent measurements of the thermal conductivity of ammonia-rich ices
      suggest that the melt pockets may be longer-lived than previously thought. We
      propose an important role in surface organic reactions for ultraviolet sunlight
      transported to the surface as chemical energy stored in acetylene and released by
      polymerization at Titan's surface.

PMID- 11570429
TI  - Stereochemical investigation of cometary matter onboard the Rosetta Lander.
AB  - At present the European Space Agency is working on one of its Cornerstone
      Missions, named "Rosetta", to be launched in January 2003 for a visit to comet
      46P/Wirtanen2 in 2011. The Rosetta spacecraft will carry a small subsatellite,
      the Rosetta Lander3 (RoLand), to be detached from the orbiter and land on the
      surface of the comet's nucleus. One of our main scientific interests is to find
      out whether chiral organic compounds in cometary matter brought to the Earth by
      cometary impacts might have had, due to corresponding enantiomeric excesses, a
      seed function in determining the handedness which is characteristic of homochiral
      compounds employed by life on Earth. For this reason we have developed an
      Experiment for the ROSETTA mission, named Cometary Sampling and Composition
      Experiment (COSAC).

PMID- 11570430
TI  - Copper homeostasis: the role of cellular transporters.
AB  - Copper transport at the cellular level is achieved by a coordinate series of
      interactions between passive and active membrane transport proteins, vesicles,
      and soluble peptides. Knowing the function of each component of this complex
      network has made the task of delineating the mechanism of intracellular copper
      homeostasis achievable.

PMID- 11570431
TI  - Melatonin in plants.
AB  - Once thought to be exclusively a molecule of the animal kingdom, melatonin has
      now been found to exist in plants as well. Among a number of actions, melatonin
      is a direct free radical scavenger and an indirect antioxidant. Melatonin
      directly detoxifies the hydroxyl radical (OH), hydrogen peroxide, nitric oxide,
      peroxynitrite anion, peroxynitrous acid, and hypochlorous acid. The products from
      each of these reactions have been identified in pure chemical systems and in at
      least one case in vivo; the interaction product of melatonin with the OH, ie.,
      cyclic 3-hydroxymelatonin, is found in the urine of humans and rats. Some of the
      products that are produced when melatonin detoxifies reactive species are also
      highly efficient scavengers. As a result, a cascade of scavenging reactions may
      enhance the antioxidant capacity of melatonin. Additionally, melatonin increases
      the activity of several antioxidative enzymes, thereby improving its ability to
      protect macromolecules from oxidative stress. Melatonin is endogenously produced
      and is also consumed in edible plants. In animal experiments, feeding melatonin
      containing foods raised blood levels of the indole. Because physiologic
      concentrations of melatonin in the blood are known to correlate with the total
      antioxidant capacity of the serum, consuming food-stuffs containing melatonin may
      be helpful in lowering oxidative stress.

PMID- 11570432
TI  - DASH without the dash (of salt) can lower blood pressure.
AB  - While the debate regarding the effectiveness of dietary sodium restriction raged,
      the Dietary Approaches to Stop Hypertension (DASH) research group showed that a
      diet rich in fruits, vegetables, and low-fat dairy products can reduce blood
      pressure in the general population and people with Stage I hypertension. The
      original DASH diet did not require either sodium restriction or weight loss--the
      two traditional dietary tools to control blood pressure--to be effective. A
      recent study from the DASH research group now finds that coupling the original
      DASH diet with sodium restriction is more effective than either dietary
      manipulation alone.

PMID- 11570433
TI  - Alcohol and mortality: if you drink, do not forget fruits and vegetables.
AB  - Moderate amounts of alcohol may have cardioprotective effects. Several studies
      reported a higher protection by the consumption of wine. The favorable effects of
      wine have been attributed to different polyphenolic compounds, among others.
      However, these biochemical compounds are also found in other beverages. In view
      of the present evidence, there is no "right" or "wrong" drink, only a "right" and
      "wrong" drinking behavior regarding absolute amounts, drinking frequency, and
      accompanying lifestyle and eating pattern.

PMID- 11570434
TI  - The American Heart Association Dietary Guidelines for 2000: a summary report.
AB  - Recently, the American Heart Association published a revision of its dietary
      guidelines. The recommendations are based on new scientific findings, and address
      the contribution of growing rates of obesity, hypertension, and diabetes to heart
      disease in the United States. The guidelines for the general public are similar
      to dietary recommendations made by other health-related groups and government
      agencies and, therefore, place a greater emphasis on the adoption of healthy
      eating patterns and behaviors rather than a singular focus on dietary fat intake.

PMID- 11570435
TI  - Regarding dietary calcium to reduce lead toxicity.

PMID- 11570436
TI  - Regarding the conversion of beta-carotene to vitamin A.

PMID- 11570437
TI  - Regarding iron and colorectal cancer risk.

PMID- 11570439
TI  - Paediatric antibiotic prescribing by general dental practitioners in England.
AB  - OBJECTIVES: The inappropriate use of antibiotics is known to be a major
      contributory factor to the problem of antimicrobial resistance. No information is
      available on how practitioners prescribe antibiotics for children. This study
      investigated the prescribing of liquid-based antibiotics for children by general
      dental practitioners in England. DESIGN: Analysis of National Health Service
      liquid-based prescriptions issued by general dental practitioners in England.
      SAMPLE AND METHODS: All prescriptions issued by practitioners in 10 Health
      Authorities in England for February 1999 were collected. All the liquid-based
      antibiotic prescriptions for children were selected and we investigated the type
      of antibiotic prescribed, whether sugar free, the dose, frequency and duration.
      RESULTS: A total of 18,614 prescriptions were issued for antibiotics. Of the 1609
      liquid-based paediatric prescriptions 88.3% were for generic and 11.7% for
      proprietary antibiotics, of which 75.5% were for amoxicillin, 15.2% for
      phenoxymethylpenicillin, 6.6% for erythromycin, 1.7% for metronidazole.
      Cephalexin, ampicillin, cephadrine and combinations of two antibiotics were also
      prescribed. There was a wide variation in dosages for all the antibiotics
      prescribed. A significant proportion of practitioners prescribed at frequencies
      inconsistent with manufacturers' recommendations and for prolonged periods, with
      some practitioners prescribing for periods up to 10 days. Only 29.1% of all the
      prescriptions issued were sugar free. CONCLUSIONS: The results of this study show
      that some practitioners prescribe liquid-based antibiotics inappropriately for
      children. This may contribute to the problem of antimicrobial resistance. Clear
      guidelines on the choice of antibiotic, dose, frequency and duration along with
      educational initiatives for GDPs might reverse this trend.

PMID- 11570440
TI  - Therapeutic and economic implications of traumatic dental injuries in Denmark: an
      estimate based on 7549 patients treated at a major trauma centre.
AB  - AIM: To analyse the type and extent of injuries presented by patients seeking
      treatment for traumatic dental injuries at a major trauma centre. Furthermore, to
      analyse acute and subsequent treatment demands and treatment costs. METHODS: A
      therapeutic and economic analysis was performed of 7549 patients treated for
      traumatic dental injuries in a major trauma centre located at the University
      Hospital in Copenhagen, Denmark. Cases were divided into uncomplicated
      (concussion, subluxation, enamel and enamel-dentine fractures) and complicated
      cases (crown fractures with exposed pulps and crown-root fractures, luxation
      injuries with displacement of the tooth and bone fractures). RESULTS: Primary
      tooth injuries were found in 2874 patients, involving 5443 teeth, among which
      62.8% had complicated injuries. Permanent tooth injuries were found in 4525
      patients, involving 10,673 teeth, among which 40.4% had complicated injuries. The
      cost of treatment (including acute trauma service, follow-up and subsequent
      restoration) was estimated to be 0.6-1 mill USD a year for the patients treated
      in this trauma centre. If this figure is transferred to the estimated trauma
      population in Denmark, a yearly cost of traumatic dental injuries appears to
      range from 2 to 5 mill USD per 1 mill inhabitants per year according to the
      treatment scenario. CONCLUSION: Thus, treatment of traumatic dental injuries
      comprises an expensive part of the health services in Denmark.

PMID- 11570441
TI  - The management of supernumerary teeth in childhood--a retrospective study of
      practice in Bristol Dental Hospital, England and Westmead Dental Hospital,
      Sydney, Australia.
AB  - This study compared the treatment provided for patients with supernumerary teeth
      in Bristol Dental Hospital with those in Westmead Dental Hospital, Sydney,
      Australia. The records of 63 children referred for removal of a supernumerary
      tooth in Bristol and 96 children in Westmead were examined, involving a total of
      215 supernumerary teeth. Differences in the treatment provided for these patients
      were found not only between the two centres but also within one centre. There
      appeared to be no standardised route by which these patients were seen and
      therefore no standardised pattern of treatment. Contact with all UK Dental
      Schools indicated that no formal treatment protocol existed for the treatment of
      children with supernumerary teeth. In addition, a permanent incisor associated
      with a conical supernumerary tooth was twice as likely to erupt spontaneously as
      one associated with a supernumerary of tuberculate form. The location of the
      supernumerary tooth also influenced the likelihood of spontaneous eruption of the
      associated permanent incisor. There is a need for a prospective randomised
      controlled trial in the future in order to develop a formal treatment protocol
      for the management of patients with supernumerary teeth. A multicentre trial is
      under development.

PMID- 11570442
TI  - Critical pH in resting and stimulated whole saliva in groups of children and
      adults.
AB  - OBJECTIVE: The concentrations of calcium and phosphate in saliva have significant
      influence on the protective mechanisms of dental hard tissues within the oral
      environment. A lower calcium concentration means: 1) a lower thermodynamic
      driving force for hydroxyapatite precipitation at normal oral pH; 2) a higher
      driving force for hydroxyapatite dissolution at low pH; 3) a lower critical pH.
      The aims of this study were to: 1. determine the calcium and phosphate
      concentrations 2. calculate the critical pH for enamel and 3. determine the
      driving forces for demineralization and remineralization in a group of children
      and adults. METHODS: In this comparative study, calcium and phosphate
      concentrations were measured in the resting and stimulated saliva of child and
      adult volunteers using a spectrophotometric system used in routine blood
      analysis. Salivary flow rates were also measured in each group. RESULTS: The
      calcium concentrations were lower in children than adults, but the phosphate
      concentrations were not significantly different. The critical pH was
      significantly higher for children than adults in both resting and stimulated
      saliva. Therefore, the thermodynamic driving forces for; (1) demineralisation at
      low oral pH, is greater, and (2) for remineralisation at normal oral pH, is
      lower, in children compared to adults. CONCLUSION: The results of this study show
      that from thermodynamic considerations alone, there is increased risk of
      demineralization in children compared with adults.

PMID- 11570443
TI  - Dental care in acute lymphoblastic leukaemia: experiences of children and
      attitudes of parents.
AB  - OBJECTIVES: To profile the dental experiences of a group of children diagnosed as
      suffering from Acute Lymphoblastic Leukaemia (ALL) and to examine: 1) how parents
      of children diagnosed as suffering from ALL perceive the importance of dental
      care; 2) parental preferences with regard to the provision of dental care for
      children with ALL. SETTING: The study was conducted in one of the 22 United
      Kingdom Children's Cancer Study Group (UKCCSG) centres. SAMPLE AND METHODS: Data
      were collected by means of a structured interview, employing an administered
      questionnaire. RESULTS: The majority of children had attended a dentist both
      prior to, and following diagnosis, though the regularity of such attendance was
      variable and the receipt of dental preventive advice inconsistent. Parents
      appeared to place a high level of importance on their children's dental care,
      with more than two-thirds expressing a preference for this to be provided within
      the Paediatric Oncology Unit. CONCLUSIONS: There is a need to establish means by
      which regular dental attendance may be encouraged and facilitated in the
      difficult circumstances posed following diagnosis. All healthcare professionals
      need to be equipped to give clear, consistent oral health advice. This, together
      with appropriate preventive measures, should be incorporated in oral care
      protocols. In accordance with the wishes of parents in this study, it is
      recommended that a comprehensive paediatric dental service be provided at all
      UKCCSG centres.

PMID- 11570444
TI  - A study on the measurement of occlusal force and masticatory efficiency in school
      age Japanese children.
AB  - AIM: The purpose of this study was to investigate the relationship between
      occlusal force and masticatory efficiency in school age Japanese children.
      SAMPLE: The subjects were 208 volunteer Japanese children from 7 to 9 years old.
      Occlusal force was measured using an MPM-3000 occlusal instrument and masticatory
      efficiency by adenosine bisodium triphosphate (ATP) particles. RESULTS: It is
      obvious from the results that the occlusal force of Japanese school age children
      is decreasing. A t-test of both masticatory efficiency and occlusal force showed
      no significant sex differences for children at 7 and 8 years old. However, 9 year
      old boys showed significantly higher values compared with 9 year-old girls in
      both measurements. No significant difference was seen between 7 and 8 year-old
      children in both measurements. However, 9 year-old children showed significantly
      higher values when compared with 7 and 8 year-old children. Occlusal force and
      masticatory efficiency were shown to be correlated with chronological age, with a
      coefficient of more than 0.6.

PMID- 11570445
TI  - Experiences from a school-based oral health promotion programme in Wuhan City, PR
      China.
AB  - OBJECTIVES: To evaluate the effect of a six-year oral health promotion programme
      for school children of Wuhan City, PR China. METHODS: The programme group (P
      group) comprised 233 children who had just entered grade 1 (1989). The programme
      provided an oral health promotion programme, and 215 12-year-old children from
      three schools participated as a control group (C-group). After the 6-year period
      of the programme (1995), all of the children had a clinical examination according
      to the criteria of the WHO and responded to a structured questionnaire on dental
      health behaviour. RESULTS: The results showed that attitudes to dental care,
      regular tooth brushing habits, use of fluoridated toothpaste, gingival health and
      dental visits, frequencies of consuming sugary drinks/foods were improved in the
      p-group when compared with the C-group. CONCLUSION: The school-based oral health
      promotion programme should be expanded.

PMID- 11570446
TI  - Traditional tooth bud gouging in a Ugandan family: a report involving three
      sisters.
AB  - It has been reported in the literature that some rural populations of Sub-Saharan
      and Eastern Africa and other isolated areas around the world, practise gouging or
      enucleation of primary tooth buds to cure childhood illnesses. The unerupted
      primary canine tooth bud is believed to be the cause of febrile illness,
      diarrhoea, and vomiting; prevalent in infants in these areas of the world. Tooth
      bud gouging has implications for the developing dentition, and is a potential
      risk to the health and life of the child. Reported prevalence ranges from 22%
      90%. From the information in this case report, the practise of tooth bud gouging
      is no longer confined to rural areas and may well be performed by communities
      that have emigrated to the UK. The three sisters described, now resident in the
      UK, suffered tooth gouging in a city clinic in Uganda. The damage caused to the
      primary and permanent dentition is described and treatment planning and options
      are suggested for each case to restore structure and function. Appropriate
      provision of healthcare and education could avoid the potential long-term damage
      to the health of the child and their developing dentition by the practise of
      tooth bud gouging, whether it occurs in the developing or developed world.

PMID- 11570447
TI  - Idiopathic noncondylar hemimandibular hyperplasia.
AB  - A female patient with 'idiopathic non-condylar hemimandibular hyperplasia' was
      followed from the age of 7.5-11.5 years. This rare disorder was characterised by
      an increase in volume of the right inferior ramus and mandibular body. It also
      included accelerated development and eruption of the teeth on the affected side,
      but no indication of enlargement of the condyle or the condylar neck. To date,
      review of the literature revealed several cases of hemimandibular hyperplasia and
      unilateral condylar hyperplasia, both of which present with enlargement of the
      condyle. However, the patient differed significantly from any previously reported
      cases, since she had no enlargement of the condyle. The above mentioned patient
      also differed from patients with hemihypertrophy, since the teeth were
      accelerated in development, but not hyperplastic. In addition, from
      histopathologic and radiographic examinations, as well as an angiogram, benign
      fibro-osseous and vascular lesions of the mandible were excluded. Although this
      is a single case report and neither the aetiology nor the pathogenesis is yet
      understood, it may suggest a new disorder of the mandible. Therefore, future
      reporting of similar cases should be encouraged.

PMID- 11570449
TI  - UK National Clinical Guidelines in Paediatric Dentistry: Treatment of intrinsic
      discoloration in permanent anterior teeth in children and adolescents.

PMID- 11570448
TI  - Tuberculous osteomyelitis of the mandible: a case report.
AB  - Osteomyelitis of jaws caused by infection with Mycobacterium tuberculosis is
      uncommon, especially in children. We present a case of tuberculous osteomyelitis
      in a young child. Its clinical presentation, with features similar to a dento
      alveolar abscess, underline the importance of considering it in the differential
      diagnosis of jaw lesions. We discuss of the diagnostic techniques, management and
      preventive measures, and stress the importance of history taking during clinical
      examination.

PMID- 11570450
TI  - Current concepts in joint replacement.

PMID- 11570451
TI  - Fibrolipomatous hamartoma of the nerve.

PMID- 11570452
TI  - Minimization of metal debris while cutting and removing orthopedic implants.
AB  - High-speed cutting burrs often throw minute particles of metal, bone, and soft
      tissue in the air during removal or revision of fracture fixation. A simple
      technique using lap sponges, water-soluble lubricant, and a smoke evacuator and
      shield can nearly eliminate soft-tissue contamination.

PMID- 11570454
TI  - Total hip and knee arthroplasty: what not to do.

PMID- 11570453
TI  - Symptomatic spur formation of bilateral proximal tibiofibular joints.
AB  - Excessive, repetitive mechanical stress of the proximal tibiofibular articulation
      during sports activity can lead to degenerative changes and a syndesmotic joint.

PMID- 11570455
TI  - Minimizing operating time: does speed kill?

PMID- 11570456
TI  - The relationship between lysis and loosening in failed anatomic medullary locking
      components.
AB  - Lysis does not cause loosening of extensively porous-coated, apparently well
      fixed femoral components. We attribute this in large part to the fact that the
      area of strongest bone ingrowth is in the femoral diaphysis remote from the joint
      space. In contrast, for the acetabular component, osteolysis can be the sole or a
      contributing factor to loosening. We attribute this difference to the fact that
      the bone-implant interface of the acetabular component is much closer to the
      joint space and more readily accessible to osteolytic damage. In the future, with
      improved bearing surfaces, lysis may occur less frequently. Whether lysis is
      diminished as a result of these new designs, the authors contend that without
      adequate initial fixation, loosening will still occur. Because of our
      observations concerning osteolysis and loosening, we are more cautious in
      revising patients for osteolyis and do not revise when osteolysis first becomes
      apparent. Rather, we closely monitor osteolysis in these patients. For us, the
      question of when to operate for osteolysis remains unanswered.

PMID- 11570457
TI  - Hydroxyapatite: a noncemented fiction.

PMID- 11570458
TI  - The all-poly cemented cup: back to the future?

PMID- 11570459
TI  - Alternatives to total hip arthroplasty in osteonecrosis of the femoral head.
AB  - While THA can provide excellent relief and functional return for patients with
      osteonecrosis, it is important to establish an early and accurate diagnosis and
      develop a treatment paradigm to seek surgical alternatives to THA for treatment
      of this condition.

PMID- 11570460
TI  - Total hip arthroplasty for developmental dysplasia of the hip.

PMID- 11570461
TI  - Dealing with post-traumatic arthrosis of the hip.
AB  - The conversion of the arthritic post-traumatic hip may be more similar to
      revision surgery than routine primary hip replacement. Careful preoperative
      planning and templating is essential. Soft-tissue balance to produce stability is
      challenging, and patients may need bracing with a THR orthosis postoperatively to
      assure soft-tissue healing and stability. Acetabular bone stock may be
      significantly compromised, and the preoperative identification of bone stock
      deficiencies may not always be possible. The surgeon should be prepared with
      adequate allograft, acetabular reconstruction rings, and alternative procedures
      such as fusion or resection arthroplasty in these challenging cases.

PMID- 11570462
TI  - Periprosthetic fractures: an operative algorithm.

PMID- 11570463
TI  - Extensively porous-coated stems in femoral revision arthroplasty.

PMID- 11570464
TI  - Avoiding proximal stress shielding: modular magic!

PMID- 11570465
TI  - Bone grafts and their substitutes: facts, fiction, and futures.

PMID- 11570466
TI  - Porous hemispherical sockets: when round is right.

PMID- 11570467
TI  - Cavity-filling components: when round isn't right.

PMID- 11570468
TI  - Identification and management of pelvic discontinuity.

PMID- 11570469
TI  - The current role of osteotomy: a vestigial procedure?

PMID- 11570470
TI  - Reevaluating the unicondylar knee arthroplasty.

PMID- 11570471
TI  - The posterior stabilized: a knee for all seasons.

PMID- 11570472
TI  - Would that it were so: save the PCL!

PMID- 11570473
TI  - No post or tether required: a deep dish will do.

PMID- 11570474
TI  - My platform moveth and that's all that's needed!

PMID- 11570475
TI  - Staying out of trouble in TKR: rules of the road.

PMID- 11570476
TI  - Exposure options in the difficult knee.

PMID- 11570477
TI  - The allograft prosthetic composite: when and how.

PMID- 11570478
TI  - Patellar options in revision total knee arthroplasty.

PMID- 11570479
TI  - The stiff total knee arthroplasty: causes and cures.
AB  - Stiffness following TKA can be related to patient factors, intraoperative
      technical errors, or postoperative surgical complications. The best management is
      prevention by providing thorough preoperative patient education, aggressive
      postoperative physiotherapy, and avoidance of technical errors.

PMID- 11570480
TI  - Managing instability following total knee replacement.

PMID- 11570481
TI  - Wound complications following total knee arthroplasty.

PMID- 11570482
TI  - Hip challenges: what would you do?

PMID- 11570483
TI  - Knee challenges: what would you do?

PMID- 11570484
TI  - Echovirus type 13--United States, 2001.
AB  - Echoviruses constitute one of the major groups of the genus Enterovirus and are
      associated with illnesses including aseptic meningitis, nonspecific rashes,
      encephalitis, and myositis (1). Echovirus 13 is an enterovirus that rarely has
      been detected in the United States, accounting for only 65 of approximately
      45,000 enterovirus isolates reported to CDC during 1970-2000. No associated
      outbreaks have been reported in this country. As of June 2001, eight state public
      health laboratories and one private laboratory had reported an increased number
      of echovirus 13 isolates to CDC, most associated with aseptic meningitis. This
      report summarizes echovirus 13 activity in the United States and highlights the
      investigation of aseptic meningitis outbreaks in Louisiana, Mississippi, Montana,
      and Tennessee. Echovirus 13 should be considered in the diff erential diagnosis
      of persons with aseptic meningitis.

PMID- 11570485
TI  - Influence of homicide on racial disparity in life expectancy--United States,
      1998.
AB  - Life expectancy (LE) is an important indicator of the health of populations.
      Since the early 1900s, when estimates of LE began to be tabulated in the United
      States, the LE of blacks has been lower than that of whites (1). Homicide, which
      disproportionately affects blacks, particularly young males, contributes to this
      difference in LE. To examine the associations between homicide, LE, and race, CDC
      analyzed 1998 mortality files from the National Center for Health Statistics
      (NCHS). This report summarizes the results of that analysis, which indicate, that
      in 1998, the LE for blacks was approximately 6 years shorter than for whites and
      that, after heart disease and cancer, homicide was the next largest contributor
      to the 6-year discrepancy. Violence prevention strategies (e.g., programs for
      youth offenders) have been implemented for the general population. More research
      is needed to determine an approach to target the male black population and to
      reduce LE disparity.

PMID- 11570486
TI  - Blood donor leukocyte reduction filters as a source of human B lymphocytes.

PMID- 11570487
TI  - Improved efficiency and reliability of RT-PCR using tag-extended RT primers and
      temperature gradient PCR.

PMID- 11570488
TI  - Non-disruptive PNA-FISH protocol for formalin-fixed and paraffin-embedded tissue
      sections.

PMID- 11570490
TI  - Rapid assessment of budding pattern by cell morphology in the yeast Saccharomyces
      cerevisiae.

PMID- 11570489
TI  - Protein estimation directly from SDS-PAGE loading buffer for standardization of
      samples from cell lysates or tissue homogenates before Western blot analysis.

PMID- 11570491
TI  - New tools for oligonucleotide fingerprinting.
AB  - Oligonucleotide fingerprinting is an attractive, high-throughput complement to
      tag sequencing methods to determine the spectrum and abundance of genes in cDNA
      libraries. This method currently relies on the sequential hybridizations of
      short, radioactively labeled DNA oligonucleotides to clone arrays. Here, we
      describe a new environment that substantially improves this technology.
      Fluorescently labeled peptide nucleic acid (PNA) oligonucleotides are used as
      hybridization probes. Hybridization results are recorded with a large-field, high
      resolution laser scanner developed for this purpose. Automated image analysis
      allows easy handling of large numbers of hybridization images. Signal
      interference effects, which limit the gridding density in the radioactive
      approach, are strongly reduced. The sensitivity of the fluorescence detection
      demonstrated permits the convenient use of nylon membranes. Hybridization data
      quality is improved, and its generation is substantially accelerated, simplified,
      and less expensive.

PMID- 11570493
TI  - High-resolution semi-quantitative real-time PCR without the use of a standard
      curve.
AB  - The repeatability and sensitivity of a simple, adaptable, semi-quantitative, real
      time RT-PCR assay was investigated. The assay can be easily and rapidly applied
      to quantitate relative levels of any gene product without using standards,
      provided that amplification conditions are specific for the PCR product of
      interest. Using the LightCycler real-time PCR machine, a serial 10-fold dilution
      series (spanning four orders of magnitude) of a 379-bp cDNA template was
      amplified, and the PCR product was detected using SYBR Green I chemistry. The
      experiment was repeated on a subsequent day. The experimental design was such
      that the data lent itself to analysis using an appropriate method for testing
      repeatability. It was found that, within a single assay, for samples assayed in
      triplicate, a difference of 23% may be reliably detected. Furthermore, when all
      of the factors that contribute to variability in the assay are taken into
      account, such as day-to-day variation in pipetting and amplification efficiency,
      a 52% difference in target template can be detected using a sample size of 4. The
      assay was found to be linear over at least four orders of magnitude.

PMID- 11570492
TI  - Colorimetric assay to quantify macromolecule diffusion across endothelial
      monolayers.
AB  - Endothelial "capillary leak", the loss of vascular integrity in response to
      noxious stimuli, is characterized by extravasation of protein-richfluidfrom
      capillary lumen into surrounding tissue interstitium. This increase in vascular
      permeability, in response to inflammatory mediators, correlates with endothelial
      cell contraction and the formation of intercellular gaps within the monolayer.
      However, in vivo assessment of paracellular solute flow between endothelial cells
      may be complicated by multiple uncontrolled parameters. In vitro examinations of
      endothelial barrier leak have relied on electrical impedence or macromolecule
      diffusion techniques to determine the details pertinent to capillary barrier
      function. In this report, a simple, sensitive, nonradioactive, colorimetric assay
      to quantify the leak of a labeled protein marker across endothelial monolayers is
      described. This procedure avoids the hazards of radioisotope labels and the
      technical limitations of electrical resistance technology.

PMID- 11570494
TI  - Parallel assessment of tyrosine phosphorylation and nuclear targeting of
      proteins.
AB  - Phosphotyrosine signaling plays a vital role in cell regulation--from receptor
      activation, through stimulation of signal networks and nuclear targeting, to
      final cellular responses. Here, we propose a new approach to monitor the spatial
      and temporal aspects of tyrosine phosphorylation and dephosphorylation. The
      method can be used to determine whether protein tyrosine phosphorylations and
      dephosphorylations occur in the cytosol or the nucleus and to ascertain whether
      such modifications are associated with nuclear traffic. Promyelocytic leukemia
      (HL-60) cells are used as the experimental model. Biotinylated cytosolic proteins
      from donor cells are used to trace nuclear transport in permeabilized recipient
      cells. Thereafter, 2-D gel electrophoresis is applied to fractionate the
      cytosolic and nuclear proteins of the recipient cells, which are subsequently
      blotted onto polyvinylidene difluoride membranes. The membranes are developed
      with streptavidin and then reprobed with anti-phosphotyrosine antibodies. The
      major advantages of the protocol are that it is simple to perform, and
      reproducible results are obtained by overlaying the patterns of biotinylated
      and/or tyrosine-phosphorylated proteins. Moreover, several hundred cytosolic and
      nuclear proteins can be analyzed in parallel. Thus, by comparing the 2-D gel
      electrophoresis maps of biotinylated and tyrosine-phosphor lated proteins, it is
      possible to determine the involvement of trafficking of the latter proteins in
      cell signaling.

PMID- 11570495
TI  - Quantitative determination of lentiviral vector particle numbers by real-time
      PCR.
AB  - Here, we describe a quantitative, DNA-based, real-time PCR approach to determine
      the number of lentivirus particles that are present in vector preparations. In
      this approach, the minus strong-stop cDNA fragment that is present in viral
      capsids serves as template for PCR. Using this technology, we found that only
      0.1%-1% of the virus particles that are present in vector preparations are
      infectious. The approach described here is rapid, reliable, and simple in concept
      and can be used to estimate both vector particles in supernatants and the number
      of infectious particles. Also, this approach can easily be adapted to a high
      throughput system by using 96-well plates and a 2-h running time.

PMID- 11570496
TI  - Activation of pRL-TK by 12S E1A oncoprotein: drawbacks of using an internal
      reference reporter in transcription assays.
AB  - In transient expression assays for transcription, a vector carrying the
      experimental reporter is usually co-transfected with a second vector containing a
      distinct reporter gene as a control. The second reporter is linked to a
      constitutive promoter driving a low-level transcription that is unresponsive to
      the experimental trans-acting transcription factors used. The use of dual
      reporters enables the normalization of the experimental gene transcription with
      respect to the control reporter transcription. This method is expected to
      minimize the inherent variability in transfection data caused by changes in cell
      density and viability, cell lysis, and the recovery of samples at various stages
      of the experiment. Here, we report that one of the most widely used internal
      control reporters, the Renilla luciferase plasmid (pRL-TK), is unresponsive to
      human tumor suppressor protein p53, a potent transcriptional regulator; however,
      the reporter transcription is enhanced by another well-known transcriptional
      regulator, the adenoviral 125 EIA oncoprotein, thereby disqualifying pRL-TK as a
      universal internal control reporter for transcription assays. Our results reveal
      the necessity of stringent experiments to test the responsiveness of internal
      control plasmids to transcriptional regulators present in the assay to avoid the
      misinterpretation of transcriptional analysis data.

PMID- 11570497
TI  - Construction of recombinant vaccinia viruses using PUV-inactivated virus as a
      helper.
AB  - Recombinant vaccinia viruses (VVs) are widely used as expression vectors in
      molecular biology and immunology and are now under evaluation for gene therapy.
      The current techniques for inserting foreign DNA into the large VV genome are
      based on either homologous recombination between transfer plasmids and VVgenomes
      or direct DNA ligation and packaging using replication-deficient poxviruses.
      Here, we describe efficient new versions of both methods that produce 90%-100% of
      the recombinant viruses. In the new homologous recombination method, VV DNA
      "arms" obtained by NotI digestion and intact transfer plasmids were used for co
      transfection. In the direct DNA ligation method, foreign DNA was inserted into a
      unique NotI restriction site of the VVgenome. In both methods, the generation of
      recombinant viruses was carried out in cells infected with a non-replicating,
      psoralen-UV (PUV)-inactivated helper VV. The convenience of these new techniques
      is demonstrated by the construction of recombinant VVs that produce E. coli beta
      galactosidase. An important feature of these strategies is that any VV strain can
      be used as a helper virus after PUV inactivation.

PMID- 11570498
TI  - Development of a new epitope tag recognized by a monoclonal antibody to
      Rickettsia typhi.
AB  - The epitope recognized by a mouse monoclonal antibody (MAb) to the crystalline
      surface layer protein of Rickettsia typhi, SRT10, was mapped to 10 amino acid
      residues (SRTag TFIGAIATDT). The oligonucleotide sequence covering the epitope
      recognized by SRT10 was inserted into a mammalian expression vector together with
      multiple cloning sites. When the SRTag was fused in frame to the coding region of
      the NCC27/CLIC1 gene and expressed in mammalian cells, the MAb SRT10 could detect
      the tagged protein by immunoblotting, immunocytochemistry, and
      immunoprecipitation. In addition to the SRT-NCC27/CLIC1, SRT10 could detect N
      terminal-tagged MEF2D and C-terminal-tagged CD4 by immunocytochemistry. We
      suggest that this specific recognition of the SRTag by SRT10 is generally
      applicable to cellular and molecular biology research that requires the
      expression and detection of fusion proteins.

PMID- 11570499
TI  - Comparative evaluation of laser-based microarray scanners.
AB  - Laboratories use different laser-based scanners to scan microarray images. To
      assess whether results from different scanners are comparable, and thus whether
      data from different laboratories can be compared, we scanned the same microarray
      slide with three commercial scanners that use different imaging techniques. After
      the acquisition of the microarray images produced by the three scanners, the
      images were quantified using a single imaging software package and protocol. The
      results were compared, and we found that the data obtained from the three
      scanners were comparable and that the variations caused by the use of different
      instruments were negligible, in spite of the fact that the scanners were based on
      different optical imaging techniques.

PMID- 11570500
TI  - Universal SNP genotyping assay with fluorescence polarization detection.
AB  - The degree of fluorescence polarization (FP) of a fluorescent molecule is a
      reflection of its molecular weight (Mr). FP is therefore a useful detection
      methodfor homogeneous assays in which the starting reagents and products differ
      significantly in Mr. We have previously shown that FP is a good detection method
      for the single-base extension and the 5'-nuclease assays. In this report, we
      describe a universal, optimized single-base extension assay for genotyping single
      nucleotide polymorphisms (SNPs). This assay, which we named the template-directed
      dye-terminator incorporation assay with fluorescence polarization detection (FP
      TDI), uses four spectrally distinct dye terminators to achieve universal assay
      conditions. Even without optimization, approximately 70% of all SNP markers
      tested yielded robust assays. The addition of an E. coli ssDNA-binding protein
      just before the FP reading significantly increased FP values of the products and
      brought the success rate of FP-TDI assays up to 90%. Increasing the amount of dye
      terminators and reducing the number of thermal cycles in the single-base
      extension step of the assay increased the separation of the FP values benveen the
      products corresponding to different genotypes and improved the success rate of
      the assay to 100%. In this study the genomic DNA samples of 90 individuals were
      typed for a total of 38 FP-TDI assays (using both the sense and antisense TDI
      primers for 19 SNP markers). With the previously described modifications, the FP
      TDI assay gave unambiguous genotyping data for all the samples tested in the 38
      FP-TDI assays. When the genotypes determined by the FP-TDI and 5'-nuclease assays
      were compared, they were in 100% concordance for all experiments (a total of 3420
      genotypes). The four-dye-terminator master mixture described here can be used for
      assaying any SNP marker and greatly simplifies the SNP genotyping assay design.

PMID- 11570501
TI  - Vector design for optimal protein expression.
AB  - Many DNA constructs are generated for protein expression studies. Translational
      properties and mRNA stability are crucial aspects that have to be accounted for
      during DNA construction. An optimized vector for protein overexpression studies
      is described considering elements in the mature mRNA that influence
      translatability and stability. Recommendations regarding vector construction for
      Xenopus laevis embryo injection are provided, based on literature and
      experimental data. The 5'untranslated region (5'UTR) should be non-regulated,
      short, unstructured, and without AUG codons. The sequence around the start codon
      should match the initiation context of the species studied (ACCAUGG, for
      vertebrates), and the open reading frame should be cloned with its own stop
      codon, followed by a G or A residue. Furthermore, the 3'UTR should be non
      regulated, and a strong polyadenylation signal must be included in DNA vectors.
      In RNA template vectors, the presence of a poly(A) or AC tail is essential for
      stability, as well as for translation efficiency in mRNA injection experiments.
      These aspects result in high-level expression of exactly the desired protein.
      Easily obtainable examples of the sequences [5'UTR, 3'UTR, and poly(A) signal]
      are suggested.

PMID- 11570502
TI  - Determination of optimal non-denaturing elution conditions from affinity columns
      by a solid-phase screen.
AB  - The purification of biological macromolecules by affinity chromatography is a
      widespread technique used to separate a protein from other biological components.
      However, this method may destroy the protein's physiological activity because
      elution conditions aimed to dissociate the protein of interest from the high
      affinity matrix often irreversibly denature it. In the present work, we have
      developed a solid-phase assay to determine the optimal elution conditions for any
      buffer (in two steps) by determining (i) the lowest buffer concentration yielding
      maximum dissociation from the immobilized component and (ii) the highest buffer
      concentration that can be used without the loss of the protein's binding
      activity. Any buffer that can be reasonably used between these defined
      concentrations is suitable for elution within this interval. The screen is easily
      performed within a few hours and only requires nanograms to a few micrograms of
      protein. As an example, we demonstrate that more than 95% of the human
      transferrin receptor bound to a transferrin-sepharose ligand affinity column can
      be eluted with full binding activity at KSCN concentrations between 232 and 414
      nM, whereas elution with urea is not suitable to purify fully functional protein.

PMID- 11570503
TI  - Detection of bacteria in environmental samples by direct PCR without DNA
      extraction.
AB  - Cultured cells and environmental samples were used directly in PCRs without the
      isolation of DNA. Serial dilution was used to eliminate the inhibitory effect of
      materials in natural samples. Primers specific for pmoA, which encodes a subunit
      of the particulate methane monooxygenase, were used to detect and quantify
      methanotrophic bacteria by direct most probable number PCR. Phototrophic bacteria
      were detected in environmental samples by direct PCR with primers specific for
      pufM, and members of the bacterial domain were detected with primers for 16S
      rDNA. Direct PCR provides a rapid, simple, and sensitive methodfor detecting and
      quantifying bacteria in environmental samples. Detection of methanotrophic
      bacteria can be applied to monitoring bioremediation.

PMID- 11570504
TI  - Detection of caspase activation in situ by fluorochrome-labeled caspase
      inhibitors.
AB  - Apoptosis is dependent on the activation of a group of proteolytic enzymes called
      caspases. Caspase activation can be detected by immunoblotting using caspase
      specific antibodies or by caspase activity measurement employing pro-fluorescent
      substrates that become fluorescent upon cleavage by the caspase. Most of these
      methods require the preparation of cell extracts and, therefore, are not suitable
      for the detection of active caspases within the living cell. Using FAM-VAD-FMK,
      we have developed a simple and sensitive assay for the detection of caspase
      activity in living cells. FAM-VAD-FMK is a carboxyfluorescein (FAM) derivative of
      benzyloxycarbonyl-valine-alanine-aspartic acid-fluoromethyl ketone (zVAD-FMK),
      which is a potent broad-spectrum inhibitor of caspases. FAM-VAD-FMK enters the
      cell and irreversibly binds to activated caspases. Cells containing bound FAM-VAD
      FMK can be analyzed by flow cytometry, fluorescence microscopy, or a fluorescence
      plate reader. Using FAM-VAD-FMK, we have measured caspase activation in live non
      adherent and adherent cells. We show that FAM-VAD-FMK labeled Jurkat and HeLa
      cells that had undergone apoptosis following treatment with camptothecin or
      staurosporine. Non-stimulated negative control cells were not stained.
      Pretreatment with the general caspase inhibitor zVAD-FMK blocked caspase-specific
      staining in induced Jurkat and HeLa cells. Pretreatment of staurosporine-induced
      Jurkat cells with FAM-VAD-FMK inhibited affinity labeling of caspase-3, -6, and 
      7, blocked caspase-specific cell staining, and led to the inhibition of
      apoptosis. In contrast, the fluorescent control inhibitor FAM-FA-FMK had no
      effect. Measurement of caspase activation in 96-well plates showed a 3- to 5-fold
      increase in FAM-fluorescence in staurosporine-treated cells compared to control
      cells. In summary, we show that FAM-VAD-FMK is a versatile and specific tool for
      detecting activated caspases in living cells.

PMID- 11570505
TI  - Bicistronic expression of ecdysone-inducible receptors in mammalian cells.
AB  - The recent emergence of inducible expression systems for mammalian cells has
      greatly facilitated the in vivo analysis of gene function. The ecdysone-inducible
      expression system is particularly attractive because of (i) extremely low basal
      expression and high-level induced expression, (ii) the lack of pleiotropic
      effects caused by the inducer or activator, and (iii) the rapid penetrance and
      clearance of the inducer. Here, we describe an improved receptor expression
      vector. The required ecdysone receptor proteins (VgEcR and RXR) are co-expressed
      from a bicistronic cytomegalovirus (CMV) expression cassette in the vector pERV3.
      The CMV promoter in this vector can be readily replaced with a cell type-specific
      promoter of interest. Using the ecdysone analogs, muristerone A or ponasterone A,
      induction ratios of up to three orders of magnitude were attained in the
      transient transfection assays and in a cell line stably transformed with both
      pERV3 and an ecdysone-inducible reporter vector. Fine control of luciferase
      expression was achieved bv varying both the induction time and inducer
      concentration. Here, we describe a set of cell lines stably transformed with the
      vector pERV3, in which the ecdysone receptors are expressed at optimal levels for
      the high-level induction of gene expression.

PMID- 11570506
TI  - Impact of genomics in drug discovery.

PMID- 11570507
TI  - Bioinformatics: use in bacterial vaccine discovery.
AB  - Bioinformatics has now become a common laboratory name for groups studying
      genomic sequences. It is composed of many different, yet interrelated scientific
      fields such as genomics, proteomics, and transcriptional profiling. The
      availability of complete genomic sequences, especially prokaryotic organisms,
      allows one to rapidly identify, analyze, and clone genes of interest. For
      bacterial vaccine discovery, one can "mine" the genomic sequence for potential
      surface targets using various algorithms, characterize these gene targets, and
      produce primers for cloning, all before one enters the wet laboratory. This
      review will focus on various genomic mining tools/algorithms available for
      predicting open reading frames and their associated annotation (if known),
      physical and functional characterization, and cellular localization. Finally,
      examples are given of how all of this is being used for the identification of
      potential bacterial vaccine candidates.

PMID- 11570508
TI  - Flow cytometric assay for the simultaneous analysis of cell-mediated cytotoxicity
      and effector cell phenotype.

PMID- 11570509
TI  - Manufacture of pure monoclonal antibodies by heterogeneous culture without
      downstream purification.

PMID- 11570510
TI  - Eliciting antigen-specific egg-yolk IgY with naked DNA.
AB  - Immunization with naked DNA was used to elicit chicken egg yolk antibodies (IgY).
      Layer hens were inoculated with plasmid DNA encoding the enhanced green
      fluorescent protein, the fusion protein of Newcastle disease virus, and VP2 of
      African horse sickness virus. IgY was extracted from egg yolks by polyethylene
      glycol precipitation. Specific antibodies were present in the yolks of eggs from
      hens immunized with each of the three different plasmids. This approach to
      raising polyclonal antibodies obviates the need to produce and purify large
      quantities of proteins for immunization and can potentially yield large amounts
      of diagnostically or therapeutically useful reagents.

PMID- 11570511
TI  - Quantitation of retroviral-mediated transfer using luciferase in living and lysed
      cells.
AB  - We have developed a murine retroviral vector containing an improved luciferase
      gene for the study of retroviral gene transfer and expression in living or lysed
      cells. We used a cytosolic form of luciferase gene (luc+) with transcriptional
      enhancements that yielded greater expression levels. The luc+ gene was subcloned
      into the retroviral plasmids pDON-AI, in which almost the entire U3 region has
      been replaced with the heterologous human cytomegalovirus immediate-early
      promoter A stable ecotropic and amphotropic retrovirus-producing cell line was
      generated with a titer 1 x 10(6) cfu/mL. NIH/3T3(tk-) cells transduced with
      ecotropic luciferase retrovirus demonstrated a high level of luminescence on the
      third day. Lysed NIH/3T3(tk-) cells demonstrated a 10-fold increase in activity
      as compared to living cultures. The creation of a new retroviral system allowed a
      substantial decrease to 5 days from the 10-14 days previously needed to evaluate
      viral transfer using the standard neomycin method. Our assay also provides a
      quantitative assessment in contrast to the beta-galactosidase detection method,
      which also takes 5-6 days but lacks quantitative evaluation. Thus, the expression
      of an integrated luc+ gene in eukaryotic cells provides a powerful tool for the
      study of retroviral gene transfer and will greatly facilitate functional studies
      in both living and lysed cells.

PMID- 11570512
TI  - far4, far5, and far6 define three genes required for efficient activation of
      MAPKs Fus3 and Kss1 and accumulation of glycogen.
AB  - In Saccharomyces cerevisiae, mating pheromones induce G1 arrest through the
      activation of two MAP kinases, Fus3 and Kss1. Here we report the isolation of
      three mutants, far4, far5, and far6, that have the novel phenotype of regulating
      both the activity of Fus3 and Kss1 and the accumulation of glycogen. A far4
      mutation constitutively activates Fus3 and Kss1, reduces glycogen, and blocks G1
      arrest in the presence of alpha factor. In contrast, far5 and far6 mutations
      increase glycogen and reduce activation of Fus3 and Kss1 by pheromone. far4,
      far5, and far6 are recessive and not allelic to FAR1, FAR3, or 14 genes known to
      regulate the pheromone response. Non-allelic noncomplementation occurs between
      far6 and both far4 and far5, suggesting that FAR6 functionally interacts with
      FAR4 and FAR5. Additional observations suggest that FAR4 has functional overlap
      with FAR3, which we also find to regulate glycogen accumulation. Our results
      suggest that the activation of the mating MAPK cascade and subsequent G1 arrest
      is influenced by a signal transduction pathway that regulates glycogen. In
      support of this possibility, we find that Fus3 is activated to a greater extent
      in a "wimp" strain with defective protein kinase A. Finally, BIM1 and BIK1 have
      been identified as CEN suppressors of far5, suggesting that the microtubule
      apparatus may regulate the ability of the pheromone response pathway to promote
      G1 arrest.

PMID- 11570513
TI  - Mechanisms involved in metalloid transport and tolerance acquisition.
AB  - Toxic metalloids such as arsenic and antimony have always been an integral part
      of the natural environment. To survive in such a hostile habitat, it is crucial
      to develop strategies to exclude toxic substances from the cell and to acquire
      tolerance. Cells remove metalloids from the cytosol either by active efflux or by
      sequestration in an internal organelle. Controlling the influx appears to be
      another way of maintaining a low intracellular metalloid content. Inside the
      cell, the metalloid can be reduced to a form that is recognised by the expulsion
      system(s). In addition, metalloid complexation and compartmentalisation
      contributes to enhanced cellular tolerance. Finally, the presence of metalloids
      activates transcription of various cellular defence genes. Metalloid-containing
      drugs are currently used to treat protozoan infections and promyelocytic
      leukaemia. Since metalloid resistance hampers efficient treatment, interest in
      identifying the mechanisms involved in tolerance acquisition has arisen. The
      possibility of using genetic approaches has made the yeast Saccharomyces
      cerevisiae a compelling model system to investigate the basis of metalloid
      tolerance at a molecular level. This review describes the recent progress made in
      elucidating the mechanisms involved in metalloid transport and tolerance in yeast
      and other organisms.

PMID- 11570514
TI  - Transposon mutagenesis reveals novel loci affecting tolerance to salt stress and
      growth at low temperature.
AB  - Using transposon mutagenesis in the haploid Saccharomyces cerevisiae strain W303
      1A we have identified genes required for growth in high salt medium, survival of
      a hypo-osmotic shock and growth at 15 degrees C. Screening 25,000 transposon
      insertions revealed a total of 61 insertions that caused salt-sensitivity; and
      those insertions affected 31 genes. Only 12 of those genes were previously known
      to be required for salt-tolerance. Among the 61 insertions, three caused general
      osmo-sensitivity. We identified one single insertion mutant in the already-known
      gene, FPS1, required for survival of hypo-osmotic shock. A total of 31 insertions
      caused failure to grow at low temperature. Those identified ten different genes,
      three of which had previously been reported to affect cold-tolerance. Four genes
      were identified in both the salt and the cold-sensitivity screen. We found
      several unusual insertion mutations: (1) insertions in or close to essential
      genes, (2) insertion in an intergenic region and (3) insertions causing stress
      sensitivity in W303-1A, while the deletion mutant in BY4741 did not show such a
      phenotype. Surprisingly, our mutant set and that reported in the large-scale
      transposon insertion project (TRIPLES,
      http://ygacmed.yale.edu/triples/triples.htm) only marginally overlap. We discuss
      some of the features of transposon mutagenesis in light of the availability of
      the complete set of yeast deletion mutants and we discuss the possible roles of
      the genes we identified.

PMID- 11570515
TI  - Cloning and disruption of a phenylalanine ammonia-lyase gene from Ustilago
      maydis.
AB  - The enzyme L-phenylalanine ammonia-lyase (PAL) catalyzes the non-oxidative
      deamination of L-phenylalanine to form trans-cinnamic acid and ammonia. This
      enzyme is universally present in higher plants and it catalyzes the starting
      reaction for a central pathway that generates hundreds of different
      phenylpropanoid metabolites. Genes encoding PAL have been identified in fungi,
      but the role of the enzyme has not been determined. We cloned and characterized a
      gene that encodes PAL from the phytopathogenic fungus Ustilago maydis and we
      constructed fungal strains carrying a null mutation in the gene. These mutants
      behaved like wild-type strains in terms of growth, mating, and pathogenicity.
      These results indicate that PAL does not play a major role in the life cycle of
      U. maydis under laboratory conditions.

PMID- 11570516
TI  - Cloning and characterisation of a polyubiquitin gene from the ectomycorrhizal
      fungus Tuber borchii vittad.
AB  - Ubiquitin is a highly conserved 76-amino acid protein implicated in the function
      of quite different vital cellular processes. In the present study, we cloned and
      sequenced a polyubiquitin gene from Tuber borchii (Ubil) that is organised in
      four tandem repeats, with two C-terminal extension amino acids, serine and
      leucine. Two introns of 116 bp and 55 bp in length were detected in the first and
      second repeats, respectively. The Ubil gene is highly expressed in mycelium and
      is less expressed in the ripe fruiting body. Southern and Northern blot analyses
      revealed a second form of the ubiquitin gene.

PMID- 11570517
TI  - Molecular characterisation and polymorphism of MinLm1, a minisatellite from the
      phytopathogenic ascomycete Leptosphaeria maculans.
AB  - A sequence-characterised amplified region marker was identified in the
      phytopathogenic fungus Leptosphaeria maculans, which generated a single-banding
      pattern corresponding to six alleles showing size polymorphism between L.
      maculans field isolates. The size polymorphism was due to 2-7 tandem repeats of
      the 23-bp motif 5' TCTTACTTACATACACACCTCCC 3'. The repeated sequence, termed
      MinLm1, shares many features specific to minisatellites, e.g. a very strong G/C
      strand asymmetry, the presence of 6-bp direct repeats at both ends of the
      sequence and its occurrence in a region rich in microsatellites such as (CT)n,
      (ATG)n, (GTG)n and (CAT)n. MinLm1 shows a very high degree of conservation of the
      bases from one repeat to another and from one isolate to another (percent match
      range: 99.6-100%), whatever their geographical or temporal relatedness. MinLm1 is
      a single-locus minisatellite located on chromosomes sized 2.79 Mb and 2.48 Mb, of
      L. maculans isolates a.2 and H5, respectively. In agricultural populations of L.
      maculans, two alleles of MinLm1 were prevalent, corresponding to 2x and 5x
      repeats of the core motif. Differences in allele frequencies were observed in
      some cropping conditions, suggesting that MinLm1 is an informative marker for
      epidemiological studies of the pathogen.

PMID- 11570518
TI  - Spontaneous loss of a conditionally dispensable chromosome from the Alternaria
      alternata apple pathotype leads to loss of toxin production and pathogenicity.
AB  - The Alternaria alternata apple pathotype causes Alternaria blotch of susceptible
      apple cultivars through the production of a cyclic peptide, host-specific toxin,
      AM-toxin. We recently cloned a cyclic peptide synthetase gene, AMT, whose product
      catalyzes the production of AM-toxin and showed that it resides on chromosomes of
      1.8 Mb or less, depending on the A. alternata apple pathotype strain. Reverse
      transcriptase (RT)-PCR, using primers specific to AMT, on laboratory sub-cultured
      strains previously shown to produce AM-toxin, identified one isolate that did not
      express the gene. A leaf necrosis bioassay confirmed an AM-toxin-minus phenotype.
      However, an original isolate of this strain which had not undergone sub-culture
      gave a positive result by both RTPCR and bioassay. Contour-clamped homogeneous
      electric field electrophoresis and Southern hybridization demonstrated the loss
      of a 1.1-Mb chromosome in the non-toxin-producing isolate. Since this chromosome
      can be entirely lost without affecting growth, but is necessary for
      pathogenicity, we propose it is a conditionally dispensable chromosome.

PMID- 11570519
TI  - Isolation and characterization of four genes encoding pyruvate, phosphate
      dikinase in the oomycete plant pathogen Phytophthora cinnamomi.
AB  - The oomycete genus Phytophthora contains some of the world's most devastating
      plant pathogens. We report here the existence in P. cinnamomi of four genes
      encoding the pyrophosphate-utilizing glycolytic/gluconeogenic enzyme pyruvate,
      phosphate dikinase (PPDK). The coding regions of the four genes are >99%
      identical. At least three of the genes comprise a small gene cluster, which may
      have arisen through recent gene duplication and inversion events. Levels of Pdk
      mRNA are low in vegetative hyphae, but increase rapidly and transiently upon
      transfer of cultures to nutrient-free media, conditions that trigger asexual
      sporulation. PPDK protein and enzyme activity levels do not show a similar
      increase during sporulation. Assays of PPDK activity in P. cinnamomi hyphal
      extracts suggest that the majority of glycolytic flux in sporulating hyphae
      probably occurs via PPDK, rather than pyruvate kinase. This finding, combined
      with the existence of Phytophthora-expressed sequence tags encoding two other
      pyrophosphate-utilizing enzymes, indicates that pyrophosphate-based metabolism
      may be important in Phytophthora. The possibility that PPDK and other enzymes of
      pyrophosphate-based metabolism may provide targets for the development of novel
      control measures for Phytophthora and other oomycete pathogens is discussed.

PMID- 11570520
TI  - Group I intron lateral transfer between red and brown algal ribosomal RNA.
AB  - How group I introns originate in nuclear ribosomal (r)RNA genes is an important
      question in evolutionary biology. Central to this issue is the multitude of group
      I introns present in evolutionarily distantly related plant, fungal, and protist
      lineages, together with an understanding of their origin and lateral transfer
      from one exon to another, between cell organelles, and between cells. These
      introns vary considerably in primary and secondary structure; and their
      provenance from a few or perhaps many mobile elements that have spread in rRNAs
      is unknown. Here we show that a novel lineage of group IC1 introns inserted at
      position 516 (Escherichia coli gene numbering) in the small subunit rRNA in
      bangiophyte red algae and a brown alga (Aureoumbra lagunensis) are specifically
      related, although their host cells are not. These bangiophyte and Aureoumbra
      introns are the only known cases that have a helical insertion in the P5b helix.
      The highly conserved primary and secondary structure of the extra P5b helix
      suggests that it is important, although its specific function is unknown. Our
      study attempts to understand the origin and movement of these IC1 introns.

PMID- 11570521
TI  - Time trends in oral health behaviors among Norwegian adolescents: 1985-97.
AB  - The purpose of this study was to investigate 1) the temporal changes in oral
      health behaviors and 2) the development of the distribution of oral health
      behaviors on the basis of socioeconomic factors among Norwegian adolescents from
      1985 to 1997. Large-scale national surveys to assess smoking, intake of sweets,
      soft drink consumption, and toothbrushing among Norwegian adolescents were
      conducted in November 1985, 1989, 1993, and 1997. The surveys were part of the
      World Health Organisation (WHO) international study, Health Behaviour in School
      aged Children. A total of 3955 (1985), 5037 (1989), 4952 (1993), and 5026 (1997)
      11-, 13-, and 15-year-old students completed anonymous questionnaires at school.
      The response rates varied from 79% to 90%. The results showed a strong increase
      in the percentages reporting ever smoking and daily intake of soft drinks and
      sweets with age from 11 to 15 years in each survey year. In 1997, at the age of
      15 years, most students reported toothbrushing more than once a day (94% boys,
      97% girls) and ever smoking (39% boys, 36% girls), whereas moderate proportions
      confirmed daily intake of soft drinks (28% boys, 19% girls). Comparison of the
      results across the survey years, from 1985 to 1997, showed an overall decrease in
      ever smoking (boys, 59% versus 39%; girls, 52%, versus 36%) and toothbrushing
      more than once a day (boys, 95% versus 94%; girls, 99% versus 97%). Contemporary
      increases occurred with regard to daily soft drink consumption. Inequalities in
      ever smoking and daily soft drink consumption between socioeconomic status groups
      decreased and increased, respectively, from 1983 to 1997. The sex disparities
      observed in 1985, with boys being more likely than girls to report ever smoking
      and daily soft drink consumption, leveled off in 1997.

PMID- 11570522
TI  - Determinants of utilization of dental services among 20- to 34-year-old Danes.
AB  - Our aim was to identify determinants of utilization of dental services among 20-
      to 34-year-old Danes as outlined in a conceptual framework. Our sample consisted
      of a sample of 464 individuals who had been interviewed by 10 experienced
      interviewers from The Danish National Institute of Social Research. Our
      questionnaire comprised a battery of questions based on our conceptual model. The
      analysis was done in a hierarchical manner using a framework with three steps:
      Predisposing factors --> Enabling factors --> Need factors --> Utilization.
      Associations were evaluated with multivariate logistic regression analysis and
      expressed as odds ratios. The following factors were significantly associated
      with irregular use of dental services: age, sex, exercise habits, cost of dental
      treatment, dental anxiety, and perceived condition of teeth. Our findings suggest
      that a strategy aiming to increase young people's dental attendance should focus
      on the transition period that is, when the youngsters leave the public dental
      health care system and have to make use of the private system. The strategy
      should also take into account that young men are more likely to become non-users.
      A concerted effort could be dedicated to the non-negligible group of individuals
      with dental anxiety and dental phobia.

PMID- 11570523
TI  - Genetic background for immune-mediated diseases.
AB  - Gene variants (alleles) involved in the immune response are most likely selected
      during evolution. The allelic polymorphisms that may be advantageous in fighting
      harmful agents may be susceptibility genes in immune-mediated diseases.
      Identification of susceptibility genes is important because these genes encode
      proteins, which are most probably involved in the disease process. Hence, the
      identification of susceptibility genes may lead to an improved understanding of
      the pathogenesis and may therefore help the development of preventive and
      therapeutic measures. Susceptibility genes may be identified by analyzing genes
      known to be involved in immune responses (candidate gene search) or by analyzing
      gene markers evenly distributed over the genome (genome-wide scan). However,
      since several genes jointly contribute to disease susceptibility, the frequencies
      of single susceptibility genes may be quite high in the normal population.
      Moreover, different set of genes may predispose to the same clinical disease. It
      may therefore be very difficult to identify susceptibility genes, apart from the
      major histocompatibility complex (MHC) genes, which have now been shown to
      predispose to several immune-mediated diseases.

PMID- 11570524
TI  - T-cell-mediated mucosal immunity in the absence of antibody: lessons from
      Helicobacter pylori infection.
AB  - Approximately 50% of humanity is infected with Helicobacter pylori. This lifelong
      infection elicits a marked host response, including a robust gastric IgA
      response. However, natural infection fails to yield protective immunity. Rather
      than providing protection, the chronic inflammatory response associated with
      natural infection can contribute to tissue damage and the pathogenesis of
      gastroduodenal disease, including atrophic gastritis, peptic ulcer, and gastric
      cancer. These immune responses are attributed to a subset of helper T cells, so
      called Th1 cells, that enhance cell-mediated immunity and induce damage to the
      gastric epithelium. Thus, it is desirable to have effective vaccines that could
      prevent and cure infection and that may modify the host response in a manner that
      prevents immune-mediated disease. Using animal models as a tool to understand the
      immunobiology of Helicobacter infections, several investigators have shown that
      effective vaccines can be developed. Thus, prophylactic and even therapeutic
      vaccines have been described in various animal models. The basis for the
      effectiveness of these vaccines appears related to their ability to alter the
      gastric immune response, from a homogeneous Th1 response to a mixed Th1 and Th2
      response. Interestingly, immunity can occur in the absence of B cells, suggesting
      that novel IgA-independent mechanisms exist that confer protection against a
      luminal infection. Thus, H. pylori infection provides a model with which new
      mechanisms of immunological protection can be identified and applied to other
      mucosal infections.

PMID- 11570525
TI  - T-cell contributions to alveolar bone loss in response to oral infection with
      Porphyromonas gingivalis.
AB  - We have previously shown that mice lacking CD4+, but not CD8+, T cells lose less
      alveolar bone loss in response to oral infection with Porphyromonas gingivalis
      than do immunocompetent mice of the same genetic background, indicating that CD4+
      T cells contribute to bone resorption. The CD4+ and CD8+ T-cell knockouts were
      produced by targeted deletions of, respectively, major histocompatibility complex
      II (MHCII) or beta2-microglobulin (producing non-expression of MHCI). Because MHC
      deletions can have other effects in addition to those on T-cell selection, we
      wanted to confirm that the lessened bone loss was truly an effect of the lack of
      T cells. Consequently, we repeated our experiments with C57B1 /6J-Tcra mice that
      have a targeted deletion of the alpha chain of the T-cell receptor (Tcra). Six
      weeks after oral infection with P. gingivalis ATCC 53977 the total bone loss at
      buccal maxillary sites was 0.28 mm in infected immunocompetent mice (P=0.002
      compared with sham-infected mice), whereas in Tcra knockouts the bone loss was
      only 0.08 mm (P=0.04 compared with shams). The T-cell-deficient mice thus lost
      70% less bone after infection than did genetically matched immunocompetent mice
      (P =0.003). These experiments confirm that T cells, and their responses to oral
      infection with P. gingivalis, help to push bone remodeling in the direction of
      net loss of bone.

PMID- 11570526
TI  - Immunodiagnosis of pemphigus and mucous membrane pemphigoid.
AB  - Pemphigus and pemphigoid are two of a group of bullous diseases affecting oral
      mucosa and skin. Mucous membrane pemphigoid (MMP) comprises a heterogeneous group
      of disorders characterized by subepithelial separation and the deposition of
      immunoglobulins and complement along the basement membrane zone (BMZ). The target
      antigens in the epithelium and BMZ determine the nature of the condition, and
      recently there have been considerable improvements in our understanding of the
      BMZ antigenic composition. Pemphigus vulgaris (PV) is characterized by
      autoantibodies of the IgG isotype to the desmosomal glycoprotein desmoglein (Dsg)
      3, whereas pemphigus foliaccus targets Dsg1, although at least 50% of PV patients
      have additional autoantibodies to Dsg1. The clinical phenotype appears to be
      determined by the relative amounts of Dsg1 and Dsg3. Patients with oral or
      mucosal PV have predominantly Dsg3 autoantibodies. The most frequently targeted
      antigen in MMP is bullous pemphigoid antigen 180 (BP180), although bullous
      pemphigoid antigen 230 (BP230), laminin 5, and beta 4 integrin are also involved.
      Circulating IgG and IgA antibodies may bind to different epitopes of BP180 namely
      the NC 16A domain or COOH -terminal domain. Pure ocular disease has been
      associated with IgA antibodies to a 45-kDa antigen and IgG antibodies to the 205
      kDa antigen b4 integrin. The use of salt-split skin substrate enables
      differentiation between epidermal and dermal 'binders'. Since both the
      specificity and the antibody titer appear to have direct relationships with the
      disease severity, and a combination of clinical score and antibody titer provides
      valuable prognostic data, these investigations should be carried out on a more
      routine basis.

PMID- 11570527
TI  - Inflammatory bowel disease: clinics and pathology. Do inflammatory bowel disease
      and periodontal disease have similar immunopathogeneses?
AB  - Inflammatory bowel disease (IBD) comprises two chronic, tissue-destructive,
      clinical entities Crohn disease (CD) and ulcerative colitis (UC) both apparently
      caused by immunological overreaction (hypersensitivity) to commensal gut
      bacteria. Under normal conditions the intestinal immune system shows a down
      regulating tone ('oral tolerance') against dietary antigens and the indigenous
      microbiota. This local homeostasis is disturbed in IBD, leading to
      hyperactivation of T helper 1 (Th1) cells with abundant secretion of interferon
      gamma and tumor necrosis factor (TNF) and production of IgG antibodies against
      commensal bacteria. In addition, UC includes genetically determined autoimmunity,
      particularly IgG1-mediated cytotoxic epithelial attack. Breaching of the
      epithelium is the best-defined event underlying abrogation of oral tolerance, but
      immune deviation caused by cytokines fiom irritated epithelial cells or
      subepithelial elements (for example, mast cells, natural killer cells,
      macrophages) may also be involved. Endogenous infection with local
      hypersensitivity likewise causes periodontal disease, reflecting 'frustrated'
      immune elimination mechanisms entertained by antigens from dental plaque.
      Altogether, perturbation of a tightly controlled cytokine network, with abnormal
      crosstalk between several cell types, apparently explains the progressive
      immunopathology of chronic inflammatory mucosal diseases in general. This adverse
      development will be influenced by numerous immunity genes, the dosage and
      potential pathogeniciy of commensal bacteria, general health, nutritional status,
      and psychological factors. Several targets for new therapy have tentatively been
      identified to block immunopathological mechanisms in IBD, and inhibition of TNF
      has a striking beneficial effect in CD, supporting a central role of this
      cytokine.

PMID- 11570528
TI  - Regulation of experimental mucosal inflammation.
AB  - Studies conducted over the past 10 years have provided ample evidence that many
      types of inflammations arising from basic abnormalities of immune regulation are
      ultimately 'funneled' through a Th1 or Th2 T cell-mediated immune reaction. Thus,
      by understanding these types of reactions and, in particular, by identifying
      their natural checkpoints, one can control the inflammation regardless of its
      more basic causes. A case in point is the inflammatory disease of the intestine
      known as Crohn disease, a disease now thought to be due to one or more
      abnormalities leading to an excessive immune response to elements of the
      bacterial microflora of the gut. Both in murine models and by study of Crohn
      disease itself, we have shown that Crohn inflammation is due to a Th1 T-cell
      abnormality involving overproduction of interleukin (IL)-12, interferon (IFN
      gamma, and tumor necrosis factor (TNF)-alpha. In addition, we and others have
      shown that treatment of mice with anti-IL-12 or other agents that downregulate
      the level of IL- 12 secretion can have a dramatic effect on the inflammation.
      This is because anti-IL-12 administration leads to apoptosis of activated Th1 T
      cells. A second checkpoint of Th1 T-cell-mediated inflammation involves its
      downregulation by the suppressor cytokine, transforming growth factor (TGF)-beta.
      We have been delivering TGF-beta to mice with experimental intestinal
      inflammation, using several novel approaches. In particular, we have successfully
      treated such mice with intranasally administered DNA encoding active TGF-beta.
      Another approach currently under investigation is delivery of TGF-beta by gene
      therapy. These and other developments in the understanding of inflammation paint
      a bright future for cytokine-based therapeutic agents. It is now apparent that
      these therapies are not only effective and safe but also potentially long
      lasting.

PMID- 11570529
TI  - Contact sensitivity reactions in the oral mucosa.
AB  - Although the role of T cells in skin contact sensitivity (CS) immune reactions
      has been intensely studied, much less is known about the regulatory properties of
      T cells in the oral mucosa. Animal experiments have shown that hapten
      sensitization of the ectodermal oral mucosa leads to antigen-specific
      hypersensitivity reactions in the skin. Furthermore, oral mucosa or skin hapten
      sensitization resulted in CS inflammatory reactions in the oral mucosa on
      challenge. The oral mucosa CS responses were similar to those found skin with
      regard to cell phenotypes and cytokines. CS-like reactions were also found in the
      oral mucosa after exposure to an irritant detergent, sodium lauryl sulfate (SLS).
      The oral mucosa reacted at smaller SLS doses than did skin. Ions and molecules
      released fron dental restorative materials (together with saliva and food and/or
      beverages) expose the gastrointestinal mucosa continuously over long time
      periods. From animal experiments we have learned that mice given antigen by
      gastric feeding, subsequently antigen-sensitized on skin, and finally elicited in
      the oral mucosa and in ear skin, showed tolerance in skin but gave simultaneous
      CS inflammatory reactions in the oral mucosa. Moreover, exposure of colon mucosa
      to antigen produced CS reactions in oral mucosa after challenge. Are there CS
      reactions in the oral mucosa? Clinical and experimental studies indicate that the
      oral mucosa can function both as induction and expression site of CS. The GI
      tract may be an important modifier of the CS inflammatory reactions seen in the
      oral mucosa.

PMID- 11570530
TI  - Pseudomonas vaccination and immunotherapy: an overview.

PMID- 11570531
TI  - A patient with an electrical burn treated by modified bilateral hemipelvectomy
      and disarticulation of the right arm.
AB  - A 23-year-old Hispanic worker sustained an electrical injury to 45% of his body
      when a crane hit a power line. Amputations of both legs, with bilateral partial
      hemipelvectomies, were required. A disarticulation of the right arm at the
      shoulder was also preformed. Resection of necrotic bowel, debridement of 95% of
      the abdominal wall, and resection of the genitalia was eventually required, with
      later reconstruction of the abdominal wall. After wound healing was complete, the
      patient was fitted with Jobst garments. A customized bucket prosthesis with a
      temperature control, to allow sitting upright, was provided. An electric wheel
      chair and a myoelectronic prosthetic arm were supplied. Rehabilitation was begun
      early.

PMID- 11570532
TI  - Early clinical experience with high-frequency oscillatory ventilation for ARDS in
      adult burn patients.
AB  - Lung protective ventilation strategies are recommended in acute respiratory
      distress syndrome to avoid ventilator associated lung injury, a recently
      characterized complication of mechanical ventilation. High-frequency oscillatory
      ventilation (HFOV) is an unconventional ventilation strategy which may achieve
      this goal. We reviewed our experience with HFOV in six severely burned patients
      with acute respiratory distress syndrome. The mean age (+/- SD) of the patients
      was 34 +/- 13 years, and the mean TBSA burn was 52 +/- 10%, with a mean full
      thickness injury of 49 +/- 12%. HFOV was initiated as "rescue therapy" in three
      patients with oxygenation failure (mean PaO2/FIO2 ratio of 71 +/- 8 and mean
      oxygenation index [OI] of 42 +/- 3) that was unresponsive to conventional
      ventilation (mean FIO2, 1.0 +/- 0; mean positive end expiratory pressure, 14.8 +/
      2.8 cm H2O; and mean inhaled nitric oxide, 20 +/- 0 ppm). In the other three
      cases, HFOV was initiated "prophylactically" as a lung protective ventilation
      strategy in an attempt to prevent further respiratory deterioration. All six
      patients showed a rapid and substantial improvement in oxygenation after
      initiation of HFOV, with significant improvements in the PaO2/FIO2 and OI by 12
      hours (P = 0.02). In four patients HFOV was also used during anesthesia and
      surgery, where a total of 10 procedures involving a mean excision and closure of
      15 +/- 7% TBSA burns was performed. Five of the six patients died, but none died
      because of oxygenation failure. In three patients death resulted from sepsis and
      multiple organ dysfunction syndrome; their mean PaO2/FIO2 was 107 +/- 31 and
      their mean OI was 30 +/- 11 immediately before death. Two patients with multiple
      organ dysfunction syndrome died after withdrawal of life support; their mean
      PaO2/FIO2 and OI were 178 +/- 31 and 18 +/- 2 respectively, at the time of this
      decision. Although HFOV had no impact on mortality, it played a useful role in
      the supportive management of burn patients with severe oxygenation failure
      unresponsive to conventional ventilation. Importantly, HFOV allowed surgery to
      proceed in patients who may have otherwise been too unstable to go to the
      operating room. As far as we are aware, this is the first report of the use of
      intraoperative HFOV in burn patients.

PMID- 11570533
TI  - Assault by burning--a retrospective review with focus on legal outcomes.
AB  - A small but significant number of adults admitted to our burn center were
      assaulted by burning. Eighty-five such cases were identified at our burn center.
      Fifteen deaths were caused by these assaults. These cases are in one sense unique
      in that in addition to the burn victim, society is also obliged to expend
      resources dealing with the assailant.

PMID- 11570534
TI  - Care of minor burn injuries: an analysis of burn clinic and emergency room
      charges.
AB  - Most burn injuries are minor in nature and can be managed on an outpatient basis.
      Such patients are usually evaluated and treated in emergency departments (ED)
      rather than in specialized outpatient burn care facilities. Although many burn
      centers maintain such facilities for the initial care of these patients, this
      practice is not commonplace because of conflicting interests of the ED and burn
      team. We first analyzed the hospital charges for all thermally injured patients
      admitted for a period of < or = 24 hours between April 1996 and August 1998. This
      was followed by an independent analysis of the hospital charges for all
      outpatient visits to the burn clinic and ED during calendar year 1998. Physician
      charges were not included in the second study. Patients admitted for < or = 24
      hours had mean hospital charges of $1185 when initially evaluated in the ED
      compared with $691 if they were directly admitted to the burn unit (P < 0.001).
      This difference was largely because of higher charges for medication, laboratory,
      radiologic studies, and the ED visit charges. In the second study the mean charge
      for care administered in the ED was $192 compared with $139 for treatment in the
      outpatient burn clinic (P < 0.0001). Patients treated in the burn clinic had
      significantly lower radiology and treatment charges but significantly higher
      pharmacy charges than patients treated in the ED. These data have supported our
      efforts to develop a walk-in burn treatment center. Such a program should not
      only result in reduced charges for care, but also enhance patient access to the
      expertise of the multidisciplinary burn team and help ensure optimal outcomes.

PMID- 11570535
TI  - Myoglobinuria and hypocalcemia after a superficial hydriodic acid burn.

PMID- 11570536
TI  - Paraquat poisoning in a burn patient.
AB  - Paraquat is a bipyridyl compound widely used as a contact herbicide. Since its
      introduction in 1962, hundreds of deaths have occurred, usually after suicidal or
      accidental ingestion. Death after dermal absorption of paraquat is uncommon, but
      has occurred after either contact with undiluted paraquat, disruption of skin
      integrity, or prolonged exposure. It is the purpose of this case report to
      describe a patient who had fatal dermal paraquat absorption after a crop-dusting
      accident in which he sustained 37% TBSA burns. After 9.5 hours of cutaneous
      exposure, a paraquat level of 0.169 mg/ml was obtained at 20 hours, the standard
      lethal dose at 16 hours being 0.16 mg/ml. In light of the apparently irreversible
      pathophysiology of paraquat poisoning with plasma levels as low as 3 mg/L,
      prevention and early intervention are the best treatments. Our patient may have
      survived an otherwise routine thermal injury had his wounds been aggressively
      irrigated in the field.

PMID- 11570537
TI  - Neuropathy after burn injury.
AB  - The purpose of this study was to evaluate the incidence of neuropathy in a
      consecutive cohort of patients with major burn injuries and investigate the
      clinical correlates for both mononeuropathy and generalized peripheral
      polyneuropathy. Of 572 patients examined, 64 (11%) patients had clinical evidence
      of mononeuropathy or peripheral neuropathy or both. Associations of
      mononeuropathy and peripheral neuropathy with potential risk factors were
      identified using logistic regression analyses. Electrical cause (odds ratio [OR]
      = 4.1022, P < .01), history of alcohol abuse (OR = 2.2893, P <.05), and number of
      days in intensive care (OR = 1.0457, P < .001) were significantly associated with
      mononeuropathy. The number of days in intensive care (OR = 1.0740, P < .001) and
      patient age (OR = 1.0543, P < .01) were significantly associated with peripheral
      neuropathy. This study demonstrates that neuropathy is a common complication of
      severe burn injury in patients who are older, critically ill, have an electrical
      cause, or history of alcohol abuse.

PMID- 11570538
TI  - Adult patients looking at their burn injuries for the first time.
AB  - A total of 222 burn nurses from 30 burn centers completed a questionnaire about
      how and when a burn patient looks at their burn wound for the first time. The
      registered nurse is most frequently with the patient when the patient sees the
      wound for the first time (n = 187; 84%). Looking at the wound is not usually a
      planned event, and it is not documented in the patient record. Nurses use verbal
      and nonverbal patient cues to determine when it is appropriate for the patient to
      look initially at the wound and combine this initial look with an opportunity to
      teach wound healing. The patient asks the nurse for an opinion about the way the
      wound looks (n = 181; 81.5%). The nurse uses silence, presence-of-self, and
      gentle encouragement with the patient while remaining positive and honest.
      Respondents reported that the patient wants the truth but also needs reassurance
      and some degree of optimism when viewing the wound for the first time.

PMID- 11570539
TI  - Inverted television and video games to maintain neck extension.
AB  - It has been the standard of care in our pediatric facility to keep patients on
      strict bedrest with the neck in hyperextension for 5 days after a neck
      contracture release or grafting. Multiple methods have been used to help maintain
      neck immobility after grafting. It has been challenging to maintain strict
      bedrest protocols, because of decreased compliance and boredom. To address this
      issue, we examined common sedentary diversional activities engaged in by
      children. We decided to use video games to facilitate the intrinsic motivation of
      play. The monitor of a video game activity was inverted and placed behind the
      head of the bed so that the child could maintain proper neck positioning. We
      found the activity to be beneficial in many aspects. It helped maintain neck
      positioning, decreased the demand for individual interventions, and provided
      opportunities for improving self-confidence.

PMID- 11570540
TI  - Travel insurance claims made by travellers from Australia for dental conditions.
AB  - BACKGROUND: Little is known about dental problems suffered by travellers abroad.
      This study was designed to investigate travel insurance claims made by travellers
      from Australia for dental conditions, particularly examining demographic factors,
      type of travel insurance coverage, nature and duration of travel, when dental
      treatment was sought during travel, use of emergency assistance, type of
      treatment, and claim outcome, including cost. METHODS: 1,289 claims submitted
      during 1998-99 to a major Australian-based travel insurance company were examined
      for dental claims. RESULTS: 104 (8.1%) claims for dental conditions were
      submitted, of which 45 (43.3%) were made by male and 59 (56.7%) by female
      travellers. The majority of claimants were in the 60 years and over age group 54
      (52.4%). Dental conditions reported required conservative (mostly fillings) 31
      (29.8%), endodontic (mostly root canal treatment) 19 (18.3%), prosthodontic 27
      (26.0%), periodontal 8 (7.7%), oral and maxillofacial surgery 2 (1.9%) and other
      or multiple 17 (16.3%) treatments. Use of the travel insurance emergency
      telephone service for dental conditions was reported in only seven cases (6.7%).
      Almost two-thirds 64 (61.5%) of claims were accepted. Claims for prosthodontic
      treatment were significantly less likely to be accepted. The majority of dental
      conditions did not require further medical investigations, 74 (71.2%). The mean
      cost of payouts to claims was AU$238.06 for males and AU$182.58 for females.
      Claims for endodontic and prosthodontic treatment were significantly more
      expensive than other types of treatment. CONCLUSIONS: Claims for dental
      conditions represent a noteworthy proportion of travel insurance claims made by
      Australian travellers abroad. More than three-quarters of claims for dental
      conditions were for conservative, endodontic or prosthodontic treatment.
      Travellers should be advised to have a dental check-up before departure overseas
      and to take care with pre-existing dental conditions, which may not be able to be
      claimed on travel insurance.

PMID- 11570541
TI  - Post-extraction complications seen at a referral dental clinic in Dar Es Salaam,
      Tanzania.
AB  - AIM: To investigate the types and magnitude of post extraction complications.
      SETTING: A referral hospital in Dar es Salaam, Tanzania. SUBJECTS: All dental
      patients who had their teeth extracted at the Muhimbili Medical Centre dental
      outpatient clinic during the study period (May September 1999). A total of 3,818
      extractions were performed under local anaesthetic in 3,732 patients. METHOD:
      Oral examination of all patients who reported back with post-extraction problems.
      RESULTS: The frequency of post extraction complications was low (1.1 per cent),
      and was mainly due to; infected sockets (48.7 per cent), followed by bleeding
      sockets (41.0 per cent) and retained roots (10.3 per cent). There were eight
      'other' complications suffered by 11 patients: necrotising fasciitis (n=l),
      herpes zoster (n=l), Ludwig's angina (n=l), infections of the submandibular
      (n=l), parapharyngeal (n=2), masticator (n=2) and submasseteric spaces (n =2),
      and reaction to local anaesthesia (2ml of 2 per cent lignocaine hydrochloride)
      (n=1). CONCLUSION: The results of this study indicate that post-extraction
      complications are few, mostly minor, self-limiting and easily treatable. The
      study does not support routine antibiotic prophylaxis or special pre-extraction
      procedures, even in this patient population with poor oral hygiene and high HIV
      seroprevalence.

PMID- 11570542
TI  - Attitude of Chinese orthodontists towards the relationship between orthodontic
      treatment and temporomandibular disorders.
AB  - OBJECTIVE: To determine the attitude of some Chinese orthodontists towards the
      relationship between orthodontic treatment and temporomandibular disorders
      (TMDs). SUBJECTS AND METHODS: 25 orthodontists, in six public hospitals (Xi'an,
      the capital of Shaanxi Province, China), were asked to complete a 10-item
      questionnaire concerning orthodontics/TMD. RESULTS: 84% of orthodontists often
      asked their patients about the signs and symptoms of TMD before orthodontic
      treatment and 92% reported examining the TMJ region. 76% of orthodontists thought
      orthodontic treatment may possibly lead to a greater incidence of TMD, while 84
      per cent claimed that orthodontic treatment might prevent TMD. Methods of
      orthodontic treatment, patient's age, and occlusal interference were regarded as
      risk factors leading to increased incidence of TMD. CONCLUSIONS: Some Chinese
      orthodontists realise the importance of the relationship between orthodontic
      treatment and TMD. Most thought that unsuitable orthodontic treatment might
      increase the development of TMD and that orthodontic treatment could prevent TMD.

PMID- 11570543
TI  - The impact of dental appearance on perceptions of personal characteristics among
      Chinese people in the United Kingdom.
AB  - OBJECTIVE: To ascertain whether dental appearance affects perceptions of personal
      characteristics among Chinese people living in the UK. DESIGN: Cross-sectional
      analytic interview study. SETTING: Public places frequented by Chinese people.
      PARTICIPANTS: Quota sample of 165 Chinese adults living in the UK. METHODS: Each
      participant was asked to make judgements about the personal characteristics of
      the subject of a single colour photograph. Fifteen photographs were used of five
      different men each with three degrees of dental disease. MAIN OUTCOMES:
      Judgements of the adjustment and social and intellectual competence of the
      subjects of the photographs. RESULTS: Participants judged subjects with less
      dental disease to be better adjusted and more intellectually competent.
      CONCLUSION: Dental appearance affected the judgements about some personal
      characteristics made by the Chinese people studied. Dental appearance may
      influence social interactions and contribute to social selection and the
      associations between health and socio-economic status.

PMID- 11570544
TI  - Dental and oral manifestations of sclerosteosis.
AB  - AIMS AND OBJECTIVES: Documentation of the oral and dental manifestations of
      Sclerosteosis. SETTING AND PARTICIPANTS: Sclerosteosis is a member of the family
      of genetic craniotubular hyperostoses. This severe progressive sclerosing bone
      dysplasia has important orofacial manifestations and a wide geographical
      distribution. Comprehensive oral and dental evaluation of eight affected adults
      in the Afrikaner community of South Africa was undertaken. RESULTS: Gross
      asymmetrical hypertrophy of the mandible was present in all eight patients,
      bilateral or unilateral facial paralysis with weakness of facial muscles due to
      facial nerve entrapment was present in six. Drooling of saliva and difficulties
      with mastication were frequent problems in these persons. The teeth were
      structurally and mechanically normal although there was partial anodontia in two
      patients and delayed eruption in another. Maxillary (palatal) and mandibular tori
      were present in every affected person. Due to the hyperostosis of the maxilla and
      mandible, tooth extraction was often a very difficult matter. There were no
      instances of post-extraction osteomyelitis of the mandible. CONCLUSIONS: Accurate
      differentiation of sclerosteosis from the other sclerosing bone dysplasias is
      crucial for effective dental prognostication and management.

PMID- 11570545
TI  - Chemomechanical caries removal: a comprehensive review of the literature.
AB  - Compared to the past, caries removal has become more efficient, however inherent
      fundamental drawbacks of the drilling approach have remained: unpleasantness to
      patients, need for local anesthesia, and potential adverse effects to the pulp
      due to heat and pressure. Chemomechanical caries removal, introduced almost three
      decades ago, was claimed to be a non-invasive alternative for the removal of
      carious dentine. In essence, the technique involved applying a solution onto the
      decayed dentinal tissue, allowing it to soften it, and, finally, scraping it off
      with blunt hand instruments. The partially degraded collagen in carious dentine
      was chlorinated by chemomechanical caries removal solutions. This chlorination
      affected the secondary and/or quaternary structure of collagen, by disrupting
      hydrogen bonding. Carious material removal was thus facilitated. The purpose of
      this paper is to perform a comprehensive review of the literature regarding
      chemomechanical caries removal, including the most recently available product,
      the initial reports on which warrant renewed interest in the approach.

PMID- 11570546
TI  - An epidemiological study of tori among 667 dental outpatients in Trinidad &
      Tobago, West Indies.
AB  - AIM: To study the prevalence of tori amongst dental outpatients, the ethnic and
      sex variations in their distribution, and their clinical features. SETTING: The
      School of Dentistry, St. Augustine, Trinidad & Tobago. PARTICIPANTS: 667
      consecutive dental outpatients representing three different ethnic groups of the
      country. METHODS: Clinical examination for and recording of tori indicating their
      location, extent and clinical features and the age, sex and ethnic grouping of
      the patient. RESULTS: The overall prevalence of tori was 12.3 per cent.
      CONCLUSIONS: There were no significant differences in the prevalence among the
      African, Indian or mixed ethnic groups of patients examined. There seemed to be
      strong link between the coexistence of palatal and mandibular tori.

PMID- 11570547
TI  - An ethnographic study for understanding children's oral health in a multicultural
      community.
AB  - OBJECTIVE: To provide guidance for a public health intervention in a high caries
      rate multicultural population by understanding cultural issues surrounding
      children's oral health. METHOD: Seven community focus groups were conducted with
      five ethnic populations (Chamorro, Filipino, Carolinian, Pohnpean, and Chuukese)
      living on the island of Saipan, Commonwealth of the Northern Mariana Islands,
      USA. Participants were asked questions about their beliefs, attitudes, knowledge,
      and care practices regarding issues around children's oral health. RESULTS:
      Analysis consisted of a content review of participants' responses within two
      targeted areas: past and current attitudes and health beliefs, and behaviours
      impacting risk of developing disease. Both the lack of value of baby teeth and
      negative parental experiences are factors underlying health beliefs and
      behaviours. Although some differences in beliefs and practices existed across
      cultural groups, most women were interested in learning about new preventive
      strategies to reduce dental disease. Several new mothers reported that they
      actively sought out parenting information during their initial pregnancy.
      CONCLUSIONS: Aversive parental experience and disregard for primary dentition
      were identified as serious obstacles to be addressed in order for any new
      programme to be effective. Despite these obstacles, new mothers were open to
      information and strategies to reduce the prevalence of early childhood caries.

PMID- 11570548
TI  - International profiles of dental hygiene 1987 to 1998: a 19-nation comparative
      study.
AB  - AIM: Development of an international longitudinal database to examine patterns,
      trends and changes in dental hygiene. METHOD: Three surveys of national dental
      hygienists' associations, mainly members of the International Federation of
      Dental Hygienists. Data were collected by mail in 1987, 1992 and 1998, using a 40
      item questionnaire. Sample size increased over time; results presented are based
      on responses for 13, 15 and 19 countries respectively. Preliminary tabulations
      were circulated to respondents for validation. RESULTS: Overall, characteristics
      of the profession were remarkably similar; most noteworthy was the scope of
      dental hygiene clinical practice. Regarding historical development, education and
      professional organisation, the profession was more similar than dissimilar.
      Greater variation was evident in terms of numbers, distribution, workforce
      behaviour, predominant work setting and remuneration. While apparent change over
      the relatively short period 1987 to 1998 was viewed with caution, several
      observations were of particular interest: marked increases in the supply of
      dental hygienists, scope of practice and range of practice settings, accompanied
      by a decline in mandated level of work supervision. A slight but gradual increase
      in independent dental hygiene practice also was noted. CONCLUSION: By 1998 the
      profiles reflected the vast majority of the world's population of dental
      hygienists. While rate of change varied across the countries examined, the nature
      of the change tended to be consistent, resulting in a continuing homogeneity in
      the profession worldwide. Changes and emerging trends should continue to be
      monitored in terms of improved access to quality oral health services and
      technical efficiency in the provision of those services.

PMID- 11570549
TI  - Cloning and sequence characterisation of falcipain-2 from Plasmodium falciparum
      Gombak A strain (Malaysia).
AB  - In this study, the genome of the Plasmodium falciparum Gombak A strain was
      examined for the presence of a gene encoding falcipain-2, a cysteine protease,
      using homology-based polymerase chain reaction cloning. The nucleotide sequence
      obtained from the gene cloned (designated pFG1) is approximately 99% homologous
      to other falcipain-2 genes from different strains. Comparatively, it is 69%
      homologous to falcipain-3 genes. Direct cloning of the falcipain-2 gene and its
      resemblance to the reported corresponding mRNA transcript suggests the absence of
      introns in this gene. Sequence alignment and comparison revealed four amino acid
      differences at positions 15, 51, 59 and 414 in the falcipain-2 from P. falciparum
      Gombak A as compared to other falcipain-2 proteins from different strains.

PMID- 11570550
TI  - Are Teladorsagia circumcincta (Nematoda) morphs equally able to survive under
      anthelmintic treatment in sheep on pastures?
AB  - The nematode Teladorsagia circumcincta is a polymorphic species, morphs T. c.
      trifurcata and T. c. circumcincta being the most frequent. Among other traits, T.
      c. trifurcata has lower infectivity than T. c. circumcincta. Anthelmintic
      treatments that regularly remove populations should favour the more infective T.
      c. circumcincta. The present investigation was intended to test the respective
      capabilities of the two morphs to withstand anthelmintic pressure. The nematode
      strain was susceptible to imidazothiazole and partly resistant to benzimidazole
      at the onset of experiment. A 2-year grazing season study was undertaken under
      four levels of anthelmintic pressure [from untreated controls to frequently
      treated with a poorly efficient benzimidazole (fenbendazole) or an efficient
      imidazothiazole (levamisole)]. The strain previously maintained in laboratory
      conditions regained its natural, original proportion of T. c. trifurcata during
      the first grazing season. The two morphs were equally resistant to fenbendazole;
      and the proportion of resistant nematodes did not vary between the two morphs.
      During the second grazing season, the treatments indirectly depleted the
      proportions of T. c. trifurcata, probably due to the poor infectivity of this
      morph.

PMID- 11570551
TI  - Release of hyaluronidase during in vitro development of Ascaris suum from the
      third to fourth larval stage.
AB  - An enzyme that degraded glycosaminoglycan hyaluronic acid was released during in
      vitro development of Ascaris suum L3 to L4. The enzyme did not hydrolyze
      glycosaminoglycan chondroitin sulfate A. One molecular form of hyaluronidase was
      detected, with a molecular weight estimated at 47.8 +/- 8.6 kDa by sucrose
      density gradient centrifugation and at 55.0 +/- 1.3 kDa by substrate SDS-PAGE
      zymography. Activity of the enzyme was optimal between pH 5.0 and 6.0, and was
      present at neutral pH. Hyaluronidase activity was not affected by 5 mM
      concentrations of cupric sulfate, zinc chloride, calcium chloride, manganese
      chloride or EDTA. In addition, NaCl had no effect on enzyme activity at
      concentrations of 0.2-1.0 M. The highest level of hyaluronidase was present in
      culture fluid collected between days 4 and 6 of in vitro culture, and this period
      corresponded with that of the highest rate of increase in the percentage of L4.
      The presence or absence of hyaluronic acid plays a key role in basic
      developmental processes of vertebrates and is regulated, in part, by
      hyaluronidases. Developmental processes occurring during the transition of A.
      suum L3 to L4 may likewise depend on hyaluronidase. In addition, the infection
      process of a number of organisms, including some nematodes, depends on
      hyaluronidase. A. suum may likewise utilize hyaluronidase to facilitate larval
      migration within the host.

PMID- 11570552
TI  - Role of chicken serum in inhibiting Leucocytozoon caulleryi development in
      Culicoides arakawae infected by membrane-feeding of infective blood meals.
AB  - Leucocytozoon caulleryi, the most important pathogen of leucocytozoonsis in
      several Asian countries, is transmitted by Culicoides arakawae. Although the
      vector blood meal factors that influence the infectivity of L. caulleryi remain
      poorly understood, the factors in infected chicken serum remain vital. C.
      arakawae blood-fed through a membrane were used in this experiment to examine the
      influence of serum factors on L. caulleryi development. Experimental results
      indicate that C. arakawae were successfully blood-fed through a chicken-egg-shell
      membrane and the serum factors in infected chicks significantly affected L.
      caulleryi sporogony. The inhibition effect of serum factors calculated from
      sporozoite averages was 53.6% +/- 2.2%. The serum factors, including transmission
      blocking antibody, require further detailed study.

PMID- 11570553
TI  - In vitro metabolism of moxidectin in Haemonchus contortus adult stages.
AB  - We studied the implication of cytochrome P450 enzymes in the in vitro metabolism
      of moxidectin (MXD) in homogenates of Haemonchus contortus adult stages
      (susceptible isolate, Weybridge, UK). After homogenisation in a phosphate buffer,
      2 ml of homogenates (equivalent to 1 g of nematodes) were incubated with 5 microg
      [14C] MXD at 37 degrees C for 24 h. MXD and its metabolites were separated by
      HPLC with radiodetection on-line. Only one metabolite was detected and its
      production was inhibited by carbon monoxide. This result demonstrates that the
      cytochrome P450 system is implicated in the metabolisation of MXD in H. contortus
      susceptible to milbemycin. Furthermore, this metabolite did not match those
      previously described in vertebrates.

PMID- 11570554
TI  - Recognition of cattle skin by cercariae of Orientobilharzia turkestanica.
AB  - The cercariae of Orientobilharzia turkestanica attached to isolated cattle skin
      and penetrated it. The attachment was stimulated by warmth and by hydrophilic and
      lipophilic chemical cues of skin surface extracts. The enduring contact with the
      skin was also stimulated by the chemical cues, but not by warmth. Penetration of
      the cercariae into agar substrates was triggered by skin surface lipids, and free
      fatty acids were identified as the exclusively active compounds of the lipids.
      That the cercariae attach and remain on the skin by responding to at least two
      different chemical host cues is unique among the schistosomatids studied so far.
      It might reflect an adaptation to invade the hosts in clear water or near the
      water surface where chemical mud compounds will not interfere with host
      recognition.

PMID- 11570555
TI  - Inflammatory response during the muscle phase of Trichinella spiralis and T.
      pseudospiralis infections.
AB  - An attempt was undertaken to determine whether a concurrent infection of
      Trichinella spiralis and T. pseudospiralis can reduce cellular infiltrations
      against the former species during the muscle phase of worm development. BALB/c,
      nude and CBA/N mice were orally infected with either species or a mixture of
      both. New-born larvae (NBL) of either or both species were also injected
      subcutaneously into the right/left leg of BALB/c mice. In T. spiralis oral
      infection, myositis was strongest in BALB/c, intermediate in CBA/N and weakest in
      nude mice. In T. pseudospiralis oral infection, slight cellular infiltrations
      were observed around the worms in BALB/c but not in nude or CBA/N mice. However,
      in mixed oral infections of two species, infiltrations around the sites of T.
      spiralis were not reduced. In mice injected with T. pseudospiralis NBL,
      infiltrations around the infective-stage larvae were mostly absent. However, in
      mice injected with T. spiralis NBL, prominent granulomatous reactions were
      observed near the sites of worms. The tissue reaction was substantially stronger
      than that in oral infections. In mice injected with NBL of both species (into
      different legs), a heavy infiltration was also observed at the site of T.
      spiralis. A marked increase in levels of IL-4 and IL-6 was detected in the
      popliteal lymphocytes of BALB/c mice injected with either live or dead NBL of T.
      spiralis at days 15 and 20 post-injection. This indicated that the worms mainly
      elicited a TH2 response during the muscle phase of development. An indirect
      fluorescent antibody test and laser confocal microscopic studies demonstrated the
      presence of CD4 and CD8 cells in the cytoplasmic region of the nurse cell complex
      of T. spiralis.

PMID- 11570556
TI  - Immune-mediated parasite clearance in mice infected with Plasmodium berghei
      following treatment with manzamine A.
AB  - Manzamine A, a sponge-derived alkaloid, was recently shown to possess in vivo
      antimalarial activity against the blood stages of the rodent malaria parasite
      Plasmodium berghei. A single intraperitoneal dose of 100 micromol/kg of manzamine
      A suppressed parasite growth but was followed by parasite recrudescence. Forty
      percent of mice with recrudescing parasites were able to recover and clear the
      fulminating parasitaemia. Examination of sera from these mice revealed that
      infected mice treated with manzamine A had a suppressed IFN-gamma production but
      an increase in their IL-10 and IgG production. The prolonged survival of infected
      mice treated with manzamine A and the eventual clearance of recrudescing
      parasites in some of these mice involve a down-regulation of Thl responses and a
      switch to antibody dependent-Th2 responses.

PMID- 11570557
TI  - Parasite-specific antibody and cellular immune responses in human infected with
      Necator americanus and Oesophagostomum bifurcum.
AB  - In this study parasite-specific antibody, cellular reactivity and Thl-type or Th2
      type cytokine responses were investigated in humans concurrently infected with
      Necator americanus and Oesophagostomum bifurcum. The prospects for O. bifurcum
      specific serodiagnosis based on IgG4 and IgE were evaluated. IgG4 showed low
      specificity for O. bifurcum due to antigen cross-reactivity with N. americanus,
      while IgE specifically distinguished between hookworm and O. bifurcum, and, in
      doubly infected patients, levels of O. bifurcum-specific as well as N. americanus
      specific IgE were significantly elevated compared to those with N. americanus
      mono-infections. Cellular immunity was not strictly dominated by a Thl- or Th2-
      type reactivity. In co-infected patients cellular unresponsiveness to parasite
      antigens was observed, while cellular production of tumour necrosis factor alpha
      (TNF-alpha) and gamma-interferon (IFN-gamma) was greater in those doubly
      infected. Th2-type cytokines (interleukin-5 and interleukin-10) were produced in
      equal amounts by peripheral blood mononuclear cells from individuals with mono-
      and coinfections. Such mixed Thl-type and Th2-type immune responsiveness
      associated with persisting gastrointestinal parasitic nematodes may reflect a
      state of infection at which parasite-induced inflammatory and enteropathogenic
      responses co-exist, and furthermore, helminth coinfection will not only suppress
      parasite-specific cellular responsiveness but may also direct cytokine production
      towards a "permissive Th1-type cytokine profile" that favours parasite
      persistence.

PMID- 11570558
TI  - Burchellin: effects on Triatoma infestans and on Trypanosoma cruzi within this
      vector.
AB  - Supplementation of blood with the neolignan burchellin (50 microg/ml), a compound
      from the arboreous Lauraceae Aniba burchelli, affected the ingestion of blood and
      the course of excretion of fourth- and fifth-instar larvae of Triatoma infestans,
      the latter especially within the first 4 h after feeding. The total resultant
      weight loss of treated fourth instars within 24 and 48 h after feeding was only
      24% and 28% vs 41% and 48%, respectively, in untreated bugs. In fifth instars,
      the total weight losses of untreated bugs within 24 and 48 h after feeding were
      38% and 41% whereas the weight of treated bugs decreased by 28% and 34%,
      respectively. In a treatment of Trypanosoma cruzi-infected fourth instars,
      burchellin significantly reduced the population density of the established
      infection in the rectum at 5 and 10 days after feeding. This was especially due
      to a significant increase in the number of the main dividing stage, the
      epimastigote.

PMID- 11570559
TI  - Purification of Anisakis simplex antigen by affinity chromatography.
AB  - In order to improve the specificity and sensitivity of the techniques for the
      diagnosis of human anisakidosis, a method of affinity chromatography for the
      purification of species-specific antigens from Anisakis simplex third-stage
      larvae (L3) has been developed. New Zealand rabbits were immunized with A.
      simplex or Ascaris suum antigens or inoculated with Toxocara canis embryonated
      eggs. The IgG-specific antibodies were isolated by means of protein A-Sepharose
      CL-4B bead columns. IgG anti-Anisakis simplex, anti-Ascaris suum and anti-T.
      canis were coupled to CNBr-activated Sepharose 4B. For the purification of the
      larval Anisakis simplex antigens, it was loaded into the anti-A. simplex column
      and bound antigens were eluted. For the elimination of the epitopes responsible
      for the cross-reactions, the A. simplex-specific proteins were loaded into the
      anti-Ascaris suum and anti- T. canis columns. To prove the specificity of the
      isolated proteins, immunochemical analyses by polyacrylamide gel electrophoresis
      and immunoblotting were carried out. Likewise, immunoaffinity columns were
      prepared using specific IgG from patients with Anisakis simplex sensitization,
      previously diagnosed by fluoro-enzymo-immunoassay. The protein patterns of
      antigen after purification by the human columns were similar to those obtained
      using the rabbit columns.

PMID- 11570560
TI  - Characterisation of single domain ATP-binding cassette protien homologues of
      Theileria parva.
AB  - Two distinct genes encoding single domain, ATP-binding cassette transport protein
      homologues of Theileria parva were cloned and sequenced. Neither of the genes is
      tandemly duplicated. One gene, TpABC1, encodes a predicted protein of 593 amino
      acids with an N-terminal hydrophobic domain containing six potential membrane
      spanning segments. A single discontinuous ATP-binding element was located in the
      C-terminal region of TpABC1. The second gene, TpABC2, also contains a single C
      terminal ATP-binding motif. Copies of TpABC2 were present at four loci in the T.
      parva genome on three different chromosomes. TpABC1 exhibited allelic
      polymorphism between stocks of the parasite. Comparison of cDNA and genomic
      sequences revealed that TpABC1 contained seven short introns, between 29 and 84
      bp in length. The full-length TpABC1 protein was expressed in insect cells using
      the baculovirus system. Application of antibodies raised against the recombinant
      antigen to western blots of T. parva piroplasm lysates detected an 85 kDa protein
      in this life-cycle stage.

PMID- 11570561
TI  - Molecular cloning of a gene encoding matrix metalloproteinase-like protein from
      Gnathostoma spinigerum.
AB  - The advanced third-stage larvae (aL3) of Gnathostoma spinigerum contain a 24 kDa
      glycoprotein with diagnostic potential. Immunoscreening with the monoclonal
      antibody to the 24-kDa protein (mAb GN6/ 24) has identified a cDNA clone with an
      insert of 932 base pairs (bp). The insert contains a full-length gene of 732 bp
      encoding a protein that is 33-39% similar to matrix metalloproteinases (MMPs) of
      Caenorhabditis elegans and several lower and higher vertebrates. The MMP-like
      protein of G. spinigerum possesses the catalytic domain, but lacks the propeptide
      and hemopexin-like domains found in other MMPs. A signal peptide of 23 amino
      acids at its amino terminus indicates that it is a secretory protein, which is
      confirmed by Western blot analysis showing the presence of the 24 kDa protein in
      the excretory-secretory products of aL3.

PMID- 11570562
TI  - Nuclear factor-kappa B plays a major role in the regulation of chemokine
      expression of HeLa cells in response to Toxoplasma gondii infection.
AB  - Toxoplasma gondii infection results in an infiltration of immune cells. The
      mechanisms responsible for triggering inflammatory cell infiltration in T. gondii
      infection are not fully understood. We report that T. gondii-infected HeLa cells
      induced nuclear factor-kappa B (NF-kappaB) activation and increased the
      expression of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1)
      mRNA. An inhibitor of NF-kappaB activation, calpain-1 inhibitor, blocked the
      chemokine secretion induced by live T. gondii. Activation of the IL-8 and NF
      kappaB transcriptional reporters was suppressed in cells co-transfected with
      IkappaB kinase beta and the IkappaBalpha super-repressor plasmids. Moreover, the
      addition of IL-1alpha increased NF-kappaB activation and IL-8 mRNA expression in
      T. gondii-infected HeLa cells. These results suggest that NF-kappaB is a central
      regulator of the chemokine response in T. gondii-infected human epithelial cells
      and that chemokine IL-8 and MCP-1 secretion might be involved in the pathogenesis
      of T. gondii, via the recruitment of neutrophils, monocytes, and lymphocytes.

PMID- 11570563
TI  - Sequence variations in the introns of the triosephosphate isomerase genes of
      Oesophagostomum dentatum and O. quadrispinulatum.
AB  - Degenerated primers were used to amplify DNA fragments of the triosephosphate
      isomerase (TPI) gene from complementary DNA (cDNA) and from genomic DNA of two
      species of porcine gastrointestinal nematodes, Oesophagostomum dentatum and
      O.quadrispinulatum. Polymerase chain reaction (PCR) fragments amplified from cDNA
      were 520 bp in size for both species, while genomic fragments were 1,035 bp for
      O. dentatum (GC-content: 45%) and 1,331 bp for O. quadrispinulatum (44%).
      Sequence analyses revealed blocks of high homology in the exons interrupted by
      more variable parts in the intron regions. Five exons were predicted from the
      genomic sequences in the conserved regions which corresponded to the respective
      cDNA sequences with 6% interspecific differences. The predicted protein sequences
      (161 amino acids) were 98% similar between the species and showed 71% similarity
      to the putative protein of Caenorhabditis elegans. As a housekeeping gene, TPI
      could be amplified from cDNA of both infectious third-stage larvae and adults.
      Interspecific variations in the non-coding regions allow the PCR-based
      differentiation of the two Oesophagostomum spp.

PMID- 11570564
TI  - Comparative studies on surface phenotypes of Theileria lestoquardi and T.
      annulata schizont-infected cells.
AB  - Phenotypes of sheep cell lines infected with Theileria lestoquardi or T. annulata
      were studied by flow cytometric analysis, following immunolabelling with a panel
      of monoclonal antibodies reacting to leukocyte differentiation antigens. Cell
      surface phenotypes of Theileria-infected sheep cell lines derived ex vivo and in
      vitro were compared, both with each other and with cell lines from cattle
      undergoing acute T. annulata infection. Besides the non-lineage specific markers
      CD45, MHC class I and MHC class II, myeloid lineage-associated antigens and B
      cell-specific markers were expressed in all five different types of line,
      suggesting that both T. lestoquardi and T. annulata had infected the same cell
      types in sheep as T. annulata in cattle, notably monocytes/macrophages and B
      cells. Lineage-specific markers were generally expressed at low frequency and
      intensity; any differences between the five types of cell lines were
      quantitative, rather than qualitative. Thus, relative rather than absolute
      differences in cell preference of sporozoites of T. lestoquardi and T. annulata
      may contribute to the differences observed in previous studies in the course of
      the infection of sheep with each of these two parasites and in the infection of
      cattle with T. annulata.

PMID- 11570565
TI  - Chemotherapeutic approaches to protozoa: kinetoplastida--current level of
      knowledge and outlook.
AB  - The possibilities for treating haemoflagellate infections (African
      trypanosomiasis) are very limited (Table 1; Mehlhorn and Schrevel 1995; Croft
      1997; Hunter 1997; Wang 1997; Trouiller and Olliaro 1998). All the available
      drugs have severe side-effects in humans and animals. Vaccination is not really
      an option, in view of the wide antigen variability. At present, there are several
      drug combinations in clinical trials: suramin/eflornithine,
      suramin/metronidazole, suramin/pentamidine, melarsoprol/pentamidine,
      melarsoprol/nifurtimox and nifurtimox/eflornithine. Some of these combinations
      were successful in treating resistant Trypanosoma brucei rhodesiense and/or T. b.
      gambiense infections (Keiser et al. 2001). In leishmaniasis, the tendency is
      still to resort to the old antimony compounds, with their severe side effects. At
      present, miltefosine is in clinical phase and is the first oral drug against
      visceral leishmaniasis (Jha et al. 1999). Two drugs are currently used against
      Chagas' disease, although these do not cure chronic effects. There is no prospect
      of novel drugs in this indication either (Pecoul et al. 1999; Morel 2000).

PMID- 11570566
TI  - Chemotherapeutic approaches to protozoa: haemosporina--current level of knowledge
      and outlook.
AB  - Chloroquine and mefloquine are available for prophylactic treatment in malaria,
      against a background of the burgeoning problem of resistance developing to
      chloroquine and related drugs (Mehlhorn and Schrevel 1995). For this reason,
      highly specific national recommendations are given out regarding prophylaxis. The
      option of a viable vaccine is currently not available. More new compounds are
      therefore urgently required, since 2-5 million of the 200 300 million infected
      people die each year. At the moment, atovaquone and artemisinin derivatives are
      of great interest, as are drug combinations such as atovaquone/proguanil (since
      1997), artemether/ benflumetol (since 1998?; Ciba-Geigy, patent WO9202217) and
      chlorproguanil/dapsone (since 2000?), as these compounds are also effective
      against multi-resistant strains of Plasmodium falciparum (Tables 1, 2; Croft
      1997; Wang 1997). Pyronaridin (since 2000?) has been discovered in a Chinese
      academy and is in clinical trials (Trouiller and Olliaro 1998; Pecoul et al.
      1999).

PMID- 11570567
TI  - Chemotherapeutic approaches to protozoa: Giardia, Trichomonas and Entamoeba-
      current level of knowledge and outlook.
AB  - The situation regarding the treatment of human Giardia and Trichomonas infections
      and the intestinal and tissue stages of Entamoeba histolytica with metronidazole
      and other 5-nitroimidazoles is currently satisfactory (Table 1; Mehlhorn 2000).
      Following correct and rapid diagnosis, the parasites are eliminated reliably and
      completely. The situation in cases of infection with Acanthamoeba (often
      involving the eyes) or with Naegleria (often involving the brain) is serious,
      however. In both cases, there is no drug of choice available. Treatment consists
      of relieving the symptoms and/or preventing local degeneration.

PMID- 11570568
TI  - Combined praziquantel and albendazole chemoprophylaxis in experimental
      hydatidosis.
AB  - The results of the chemoprophylaxis of experimental hydatidosis with a
      combination of praziquantel and albendazole are presented. In vivo studies were
      performed on NMRI mice injected with protoscolices of Echinococcus granulosus.
      The treatment was the same as that previously used by us, but reducing the
      treatment period to only 1 month. Four months after injection , the mice were
      killed and autopsied. Developed hydatid cysts were counted, weighed and processed
      for observation by transmission electron microscopy. The efficacy of the present
      treatment was 97.7% and 97.15%, in number and weight of the cysts respectively,
      only slightly lower than that obtained by us after 4 months of treatment.
      Moreover, the few cysts that had developed in the treated mice showed severe
      damage to their ultrastructure.

PMID- 11570569
TI  - Helminth fauna of the European mole (Talpa europaea Linnaeus, 1758) in
      Belorussian Polesie.

PMID- 11570570
TI  - Helminth fauna of the common shrew (Sorex araneus Linnaeus, 1758) in ecosystems
      of Belorussian Polesie transformed by reclamation.

PMID- 11570571
TI  - Impact factor--online first publication.

PMID- 11570572
TI  - Association of tumor growth on nude mice and poor clinical outcome in soft tissue
      sarcoma patients.
AB  - PURPOSE: Permanent growth in nude mice (PGNM) may be associated with poor
      clinical outcome. We tested this hypothesis in a group of soft tissue sarcoma
      (STS) patients. METHODS: Small chunks from fresh tumor biopsies of 81 patients
      with STS were transplanted subcutaneously into NMRI-nu/nu nude mice. Tumor cell
      lines exhibiting growth in nude mice for more than three tumor passages were
      considered as permanently established. Clinical outcome of all patients was
      monitored with a median follow-up of 38 months. RESULTS: 39/81 (48%) STSs
      exhibited PGNM. High grade, high S-phase proportion, and aneuploidy were
      significant predictors of PGNM. Overall survival (OS) at 3 years was 21% (+7%
      standard error of median) for STS patients with PGNM and 53% (+/-8%) for patients
      without PGNM (P<0.01). Considering only patients without distant metastasis at
      the time of biopsy (n = 49), 3-year-OS was 25% (+/-10%) and 71% (+/-9%) for STS
      with PGNM and without PGNM, respectively (P<0.01). In the univariate analysis,
      PGNM, aneuploidy high S-phase proportion, tumor location at the trunk, high tumor
      grade, and non-liposarcoma histology were associated with reduced survival time.
      In the multivariate analysis, aneuploidy and tumor location at the trunk were the
      only independent predictors of overall survival. CONCLUSION: Permanent growth of
      STS on nude mice is associated with poor clinical outcome in the univariate
      analysis, but is not an independent predictor of survival in the multivariate
      analysis due to a strong co-correlation to other known adverse prognostic
      factors.

PMID- 11570573
TI  - Cyclin D1 expression and retinoblastoma gene protein (pRB) expression in
      esophageal squamous cell carcinoma.
AB  - PURPOSE: Alterations in the cell cycle regulatory cyclin/retinoblastoma protein
      (pRB) pathway play a important role in tumor progression in esophageal squamous
      cell carcinoma (ESCC). In the present study, we evaluated the prognostic
      significance of the combined analysis of cyclin D1 and pRB in ESCC
      retrospectively. METHODS: Immunoreactivities of cyclin D1 and pRB were evaluated
      in 148 surgically resected ESCC by use of monoclonal antibodies. Disease-free
      survival of patients was compared among the four subgroups according to the
      phenotypes of cyclin D1 and pRB expressions. RESULTS: High immunoreactivities of
      pRB and cyclin D1 were detected in 64.2% and 40.5% of tumors, respectively. The
      loss of pRB expression and overexpression of cyclin D1 correlated with short
      survival. However, these factors were not detected as independently prognostic in
      multivariate analysis. In 107 surviving patients who underwent curative
      operation, co-expressed pRB and cyclin D1 (pRB+/cyclin D1 +: 29 patients) were
      correlated with unfavorable prognosis (disease-free 5-year survival rate: 42.7%)
      and high cancer recurrence rate (44.8%) compared with that of 40 patients with
      pRB +/cyclin D1- tumors (70.5% and 27.5%). The disease-free 5-year survival rate
      of patients with pRB+/cyclin D1- tumors was significantly better than that of
      other groups (P=0.001). However, the disease-free 5-year survival rate of 29
      patients with pRB+/cyclin D1 + tumors was equivalent to that of 29 patients with
      pRB-/cyclin D1tumors (48.3%), and that of nine patients with pRB-/cyclin D1+
      tumors (22.2%, P=0.237). CONCLUSIONS: Our results suggest that overexpression of
      cyclin D1 may suppress pRB function, and that combined analysis of pRB and cyclin
      D1 may be a useful parameter of patient prognosis in ESCC.

PMID- 11570574
TI  - Expression of cell-cycle regulatory proteins in endometrial carcinomas:
      correlations with hormone receptor status and clinicopathologic parameters.
AB  - PURPOSE: The normal human endometrium is characterized by hormone-dependent
      variations in the levels of cell-cycle regulatory proteins during the menstrual
      cycle. As this tightly controlled system is disturbed in endometrial carcinomas,
      we analyzed which cell-cycle regulators are involved in endometrial
      carcinogenesis. METHODS: We performed Western blot analysis of five cell-cycle
      stimulating (cyclins D1, E, B1, cdk2, cdk4) and three cell-cycle inhibiting
      (p16(INK4a), p21(WAF1), Rb) proteins in 41 endometrial carcinoma specimens. In
      addition, expression of the estrogen and progesterone receptors (ER, PR), Ki67,
      and, in selected cases, p16, cyclin E, and cyclin B1 was studied by
      immunohistochemistry. RESULTS: We found upregulation of all analyzed cell-cycle
      regulators in most tumors compared to normal endometrial tissue samples.
      Overexpression of cyclin E, cyclin B1, and p21 was associated with a less
      differentiated phenotype. In addition, high levels of cyclin E, cdk2, and cdk4
      correlated with weak/absent ER expression, and p16 and p21 overexpression was
      significantly associated with low PR immunoreactivity. Cyclin B1 expression
      correlated with cyclin E, cdk2, cdk4, p21, Rb, and Ki67, and cyclin E expression
      with cyclin D1 and Rb. CONCLUSIONS: We conclude that cyclin E and cyclin B1 might
      be the major cell-cycle regulators involved in proliferation and reduced
      differentiation of endometrial carcinomas. In addition, p16, p21, and Rb appear
      to be uncoupled from their normal cell-cycle inhibiting function in many
      endometrial carcinomas.

PMID- 11570575
TI  - Expression pattern of the AP-1 family in endometrial cancer: correlations with
      cell cycle regulators.
AB  - PURPOSE: To study the expression pattern and the role of the AP-1 (activating
      protein-1) family of transcription factors in endometrial carcinogenesis.
      METHODS: We performed Western blot experiments with specific antibodies for each
      of the AP-1 proteins (c-jun, junB, junD, c-fos, fosB, fra-1, fra-2) with 41
      endometrial carcinomas. Expression levels of the AP-1 factors were correlated
      with clinico-pathologic tumor parameters, steroid receptor status, Ki-67
      expression and the expression levels of eight cell cycle regulatory proteins
      (cyclin D1, cyclin E, cyclin B1, cdk2, cdk4, p16, p21, and Rb). RESULTS: Of the
      seven AP-1 factors, three (c-fos, fra2, and junB) clearly showed higher
      expression levels in tumors when compared to matched normal endometrial samples.
      These factors also correlated significantly with cell cycle promoters (c-fos with
      cyclin E, cyclin B1, cdk2, and cdk4; fra-2 with cyclin B1; and junB with cyclin
      D1). Furthermore, high c-fos expression correlated with low ER and PR
      immunoreactivity and high grading (G3). On the other hand, correlations with
      classic cell cycle inhibitors (Rb, p16, p21) have also been observed for all AP-1
      factors except c-jun and junD. CONCLUSIONS: Our results indicate that the AP-1
      family of transcription factors is probably implicated in the regulation of cell
      cycle progression and control in endometrial carcinomas. In particular, c-fos
      might be an additional negative prognostic factor and/or implicated in tumor
      progression in endometrial cancer.

PMID- 11570577
TI  - The potential of plasma thrombomodulin as a biomarker of portal vein tumor
      thrombus in hepatocellular carcinoma.
AB  - PURPOSE: To study the relationship between thrombomodulin (TM) plasma levels and
      the formation of portal vein tumor thrombus (PVTT) in patients with
      hepatocellular carcinoma (HCC). METHODS: Pre- and-postoperative plasma TM levels
      of 45 patients with HCC and six patients with benign liver-occupying lesion were
      measured by enzyme-linked immunosorbent assay (ELISA), and the expression of TM
      in human HCC tissues was determined by immunohistochemistry assay. RESULTS: The
      preoperative plasma TM level of patients with HCC (10.2+/-5.7 ng/ml) was
      significantly higher than that of those patients with benign liver-occupying
      lesion (6.1+/-2.2 ng/ml) and that of normal controls (5.7+/-1.0 ng/ml),
      respectively (P<0.05). The postoperative TM level of 40 patients with HCC whose
      tumors had been removed decreased significantly than the preoperative TM level
      (10.8+/-5.3 ng/ml versus 7.6+/-4.2 ng/ ml, P < 0.05), whereas there was no
      significant difference between the preoperative and postoperative TM level of six
      patients with benign liver-occupying lesion (6.1+/-2.2 ng/ml versus 5.9+/-1.8
      ng/ml, P>0.05). The preoperative plasma TM level of patients with single HCC
      (11.5+/-5.9 ng/ml) or no PVTT (11.4+/-5.6 ng/ml) was significantly higher than
      that of those patients with multiple HCC (8.1+/-4.6 ng/ml) or PVTT (6.9+/-4.5 ng/
      ml), respectively (P<0.05). The preoperative plasma TM level of the patients with
      HCC tissue that stained positive for TM was significantly higher than those with
      tissue that stained negative for TM (12.2+/-6.5 ng/ ml versus 8.7+/-4.6 ng/ml,
      P<0.05). The postoperative plasma TM level showed no difference between the
      patients with HCC tissue stained positive and negative for TM (8.3+/-4.1 ng/ml
      versus 7.6+/-4.4 ng/ml, P>0.05). There was also no significant difference between
      the plasma TM level and other clinicopathological futures. CONCLUSIONS: Plasma TM
      increases in patients with HCC and can be a biomarker of the formation of PVTT.

PMID- 11570578
TI  - Comparison of Alu-PCR, microsatelite instability, and immunohistochemical
      analyses in finding features characteristic for hereditary nonpolyposis
      colorectal cancer.
AB  - PURPOSE: To evaluate and compare alterations detected by Alu-PCR, microsatellite
      instability (MI), and absence of hMLH1 and hMSH2 protein expression measured by
      immunohistochemical (IHC) analyses as features characteristic of hereditary
      nonpolyposis colorectal cancer (HNPCC). METHODS: Alu-PCR, MI, and IHC analyses
      were performed in two groups of patients: (A) HNPCC diagnosed definitively or
      with high probability (11 patients); (B) sporadic late-onset colorectal cancers
      (15 patients). RESULTS: Quantitative alterations recorded by Alu-PCR were not
      characteristic for Lynch syndrome, occurring more frequently in sporadic late
      onset CRC (73% in group B vs 45% in group A). Qualitative changes (occurrence of
      additional peaks or shifts) have been found to be associated with HNPCC with odds
      ratio (OR) 2.4, specificity approximately 70% and sensitivity approximately 55%.
      Findings in MI and IHC analyses have been recognized as features more
      characteristic of HNPCC suggesting Lynch syndrome with OR 4.8, specificity
      approximately 80%, sensitivity approximately 55% (MI) and OR 8.0, specificity
      approximately 93%, sensitivity approximately 36% (IHC). CONCLUSION: Molecular
      techniques allowing identification of patients with a high probability of having
      HNPCC include IHC and MI analyses. Our results suggest that their replacement by
      Alu-PCR analysis in diagnosis of HNPCC is not justified.

PMID- 11570576
TI  - A novel tumor-associated mucin of gastrointestinal carcinoma.
AB  - PURPOSE: To identify a new tumor-associated antigen, a monoclonal antibody,
      SC142, was produced by immunizing mice with a stomach cancer cell line. The tumor
      specificity of mAb SC142 was studied by immunohistochemical staining, and the
      biochemical characteristics of this new gastrointestinal tumor-associated antigen
      were also studied. METHODS: The expression of SC142-reactive antigen was
      investigated in various cancers by immunohistochemical staining. The SC142
      reactive antigen was characterized by immunoblotting, sodium metaperiodate
      treatment assay, O-glycanase digestion assay, and lectin binding assay. RESULTS:
      The SC142-reactive antigen was highly expressed in 78% of gastric cancers (29/37)
      and 87% of colon cancers (27/31). No normal colon or stomach tissues remote from
      the tumor were positive for the antigen. The antibody also reacted with other
      tumors of epithelial origin such as lung squamous cell cancer (2/4), breast
      ductal cancer (2/20), bladder transitional cell carcinoma (4/6), and uterine
      cancer (3/16). Western blot analysis of the antigen revealed glycoprotein(s)
      which migrated as a smear ranging from the origin of the gel to about the 80 kDa
      region. The reactivity of this antigen with SC142 was reduced by sodium
      metaperiodate treatment or O-glycanase digestion, but not by N-glycanase,
      suggesting that the epitope is an O-glycan. In lectin-binding assay, this antigen
      reacted only with wheat germ agglutinin but not with Ricinus communis agglutinin,
      Datura stramonium agglutinin, and Sambucus nigra agglutinin. CONCLUSIONS: Our
      findings indicate that the antigen defined by SC142 is a tumor-associated antigen
      that could differentiate the gastrointestinal cancer cells from the normal cells.
      Therefore, SC142 may become a valuable tool for the immunohistochemical diagnosis
      and tumor immunoscintigraphy of the gastrointestinal cancer patients.

PMID- 11570579
TI  - Thymidine-dependent attenuation of the mitochondrial apoptotic pathway in
      adenosine-induced apoptosis of HL-60 cells.
AB  - OBJECTIVE: We previously reported that adenosine-induced apoptosis in HL-60 cells
      was attenuated by cotreating the cells with pyrimidine nucleosides. The mechanism
      involved in this adenosine-induced apoptosis by the differential supply of
      nucleosides is studied here with a particular focus on the regulation of
      apoptosis-associated mitochondrial events. METHODS: Time-dependent changes in the
      mitochondrial membrane potential (MMP) after treatment with adenosine and/or
      thymidine were monitored. RESULTS: The cells did not show any decrease of MMP
      level up to 2.5 h after 1 mM adenosine exposure, whereas cytochrome c release,
      caspase-9 and caspase-3 activity, and DNA fragmentation were already activated,
      suggesting that mitochondrial depolarization is not a prerequisite of other
      apoptosis-related mitochondrial events. In contrast, the translocation of Bax to
      mitochondria and the release of cytochrome c began within the first hour of
      adenosine treatment. CONCLUSION: Thus, it is believed that adenosine-induced
      apoptosis is mediated by the activation of the caspase cascade by cytochrome c
      release with concomitant increase of Bax in the mitochondria, which implies that
      the translocation of Bax might be a leading event in the adenosine-induced
      apoptosis. Moreover, we found that most of the apoptotic parameters in adenosine
      induced cellular changes, such as translocation of Bax, the release of cytochrome
      c, and the consequent activation of caspase-9 and caspase-3, were attenuated by
      thymidine supplement, thus indicating that the sensing of a nucleoside or
      nucleotide balance might be an upstream event of cytochrome c release. Therefore,
      it can be concluded that thymidine can attenuate adenosine-induced apoptosis by
      modulating the earliest stage of the mitochondrial apoptotic pathway.

PMID- 11570580
TI  - Mutation and overexpression of the beta-catenin gene may play an important role
      in primary hepatocellular carcinoma among Chinese people.
AB  - AIM: To study the role of beta-catenin gene mutation and expression in
      hepatocellular carcinogenesis. METHOD: Thirty-four hepatocellular carcinoma (HCC)
      specimens and adjacent para-cancerous tissues, and four normal liver tissues were
      analyzed. Subcellular distribution of beta-catenin was examined by
      immunohistochemistry staining. Mutation and semiquantitative expression of beta
      catenin gene exon 3 mRNA were detected by RT-PCR-SSCP and in situ hybridization.
      RESULT: Immunohistochemistry showed that all normal liver tissues and para
      cancerous tissues examined showed membranous-type staining for beta-catenin
      protein, frequently with weak expression in the cytoplasm, but no beta-catenin
      accumulation in nuclei was found; while in liver cancer, 21 cases (61.8%) of HCC
      examined showed accumulated type in cytoplasms or nuclei. On SSCP, 15 cases
      (44.1%) of HCC altogether displayed three kinds of characteristic mutational
      mobility shifts. No abnormal shifting bands were found in tissues from normal
      liver or para-cancerous area. The beta-catenin gene exon 3 mRNA expression index
      of 34 HCCs was higher than that of para-cancerous tissue and normal liver tissue.
      Using in situ hybridization, the signal corresponding to beta-catenin gene exon 3
      mRNA was particularly strong in cytoplasm of HCC when compared with those of
      paracancerous tissues and normal liver tissues. CONCLUSION: beta-catenin gene
      mutation and overexpression may have a critical role in malignant progression of
      hepatic carcinogenesis among Chinese people.

PMID- 11570581
TI  - Cytotoxic T cells infiltrating a glioma express an aberrant phenotype that is
      associated with decreased function and apoptosis.
AB  - In this study, we report on novel alterations found in rat intracranial (i.c.)
      tumor-infiltrating T lymphocytes (TIL) that are indicative of T cell defects and
      death. FACS analysis showed that the cytotoxic T cells (CTL) infiltrating rat
      T9.F gliomas were CD3epsilon+, alphabetaTCR+, CD8alpha+, but CD8beta-. These
      lymphocytes also stained positive for the B cell-specific marker, CD45RA, as well
      as Annexin-V, signifying apoptotic changes. Functional and biochemical analyses
      were performed to assess whether the aberrant phenotype was linked to other
      defects. When CD8alpha+ TIL were purified and stimulated in vitro, their
      proliferative capacity was markedly diminished in comparison with
      CD3+CD8alpha+CD8beta+ T cells isolated from the spleens of naive, non tumor
      bearing rats. Furthermore, the mean fluorescence intensity of surface CD3epsilon
      was dramatically reduced in the CD3+CD8alpha+CD8beta- TIL population as compared
      with CD3-CD8alpha+CD8beta+ TIL from the same tumor-bearing animal. Biochemical
      studies revealed that the expression of TCRzeta and LAT were reduced in lysates
      generated from CD8alpha-purified TIL with respect to CD8alpha-purified T cells
      from naive spleen. We believe that these degenerative changes are reflective of
      chronic T cell receptor ligation, because in vitro culture of rat splenocytes or
      purified T cells with ConA or anti-CD3 mAb induced the same alterations. In
      vitro, the downregulation of CD8beta could be inhibited by the caspase inhibitor,
      z-VAD. These results suggest that the aberrant CTL phenotype found in the TIL of
      glioma-bearing rats may be novel signals for their impending death and
      degenerating anti-tumor immune function.

PMID- 11570582
TI  - Murine hypodense eosinophils induce tumour cell apoptosis by a granzyme B
      dependent mechanism.
AB  - PURPOSE: Eosinophils have been shown to potentiate anti-tumour cytotoxicity in
      both clinical and animal studies. The mechanism by which eosinophils induce
      tumour cell damage, however, has largely been speculative. The purpose of this
      study was to identify the mechanisms involved in eosinophil-induced tumour cell
      cytotoxicity. METHODS: To investigate eosinophil cytotoxicity, eosinophils were
      isolated from the peritoneal cavity of Mesocestoides corti-infected BALB/c mice,
      and were separated into normodense (ND) and hypodense (HD) populations using
      discontinuous Percoll density gradient centrifugation. The tumoricidal activity
      of ND and HD eosinophils was assessed using the [51Cr]-release cytotoxicity assay
      (a measure of cytolytic activity) and the JAM assay (a measure of apoptotic
      activity). Investigation of apoptosis-inducing molecules in HD eosinophils was
      undertaken by RT-PCR. The calcium chelator EGTA, serine protease inhibitor
      aprotinin and a competitive substrate for granzyme B were used to assess the role
      of perforin and granzyme B in HD eosinophil killing. RESULTS: Cytotoxic activity
      induced by HD eosinophils was significantly greater than that of ND eosinophils,
      and apoptosis was the principal killing mechanism. RT-PCR analysis revealed that
      HD eosinophils express mRNA for perforin, granzyme B and Fas ligand. Furthermore,
      HD eosinophil killing was markedly inhibited by EGTA, intracellular aprotinin and
      the granzyme B competitive substrate. CONCLUSIONS: These data are consistent with
      a hypothesis that murine HD eosinophils elicit tumoricidal activity via a
      granzyme B-dependent mechanism.

PMID- 11570583
TI  - Monocyte and monocyte-derived macrophage secretion of MCP-1 in co-culture with
      autologous malignant and benign control fragment spheroids.
AB  - This study was performed in order to determine how monocytes and macrophages in
      co-culture with autologous head and neck squamous cell carcinoma (HNSCC) tumor
      tissue regulate the secretion of monocyte chemotactic protein-1 (MCP-1). The
      levels of MCP-1 were measured when autologous monocytes or monocyte-derived
      macrophages (MDMs) were co-cultured in vitro with autologous fragment (F)
      spheroids established from HNSCC tumors or benign mucosa serving as control. MCP
      1 secretion from co-culture stimulated monocytes and MDMs was increased compared
      to spontaneous MCP-1 secretion. With prolonged co-culture, MDMs showed a steady
      state MCP-1 secretion above background levels for up to 96 h, even with change of
      co-culture media every 24 h. Addition of an anti-MCP-1 antibody to the medium
      decreased co-culture-induced monocyte IL-6 secretion. Addition of
      lipopolysaccharide (LPS) (1 [microg/ml) reduced MCP-1 secretion compared to
      spontaneous secretion in monocyte cultures. F-spheroids also secrete MCP-1, but
      at insignificant levels compared to the MCP-1 secretion from monocytes and MDMs.
      MCP-1 secretion from monocytes/MDMs is regulated differently when co-culture
      stimulation is compared to LPS-stimulation. Monocytes and MDMs expressed MCP-1
      mRNA at a high level in all tested conditions: stimulated in co-culture, not
      stimulated or stimulated with LPS, indicating post-transcriptional regulation of
      MCP-1 secretion. The secretion of MCP-1 from tumor-derived F-spheroids, and the
      maintenance of co-culture MCP-1 secretion from MDMs in vitro, suggests that tumor
      associated macrophages are a source of MCP-1 in HNSCC tumors.

PMID- 11570584
TI  - Ex vivo generation of human anti-melanoma autologous cytolytic T cells by
      dentritic cell/melanoma cell hybridomas.
AB  - Due to their central role in controlling immunity, dendritic cells are logical
      targets for priming naive cytotoxic T lymphocytes against tumour cells. In a
      strictly autologous system, we fused dendritic cells with melanoma cells, both of
      which were derived from patients with metastatic malignant melanoma. Hybridomas
      were positive for major histocompatibility complex (MHC) class II, CD40, CD54,
      CD83, CD86, and the pro-inflammatory cytokine interleukin-12. Autologous T
      lymphocytes were co-incubated with hybridomas. After 6 days, in-vitro-primed T
      lymphocytes revealed a strong proliferation activity and released Th-1
      associated, but not Th-2-associated, cytokines. Furthermore they showed effective
      anti-melanoma activity, resulting in death of 70 +/- 9% of autologous melanoma
      cells. After depletion of CD4+ cells from the mixed population of primed T
      lymphocytes, the remaining CD8+ cells were able to kill 63+/-8% of autologous
      melanoma cells. Following depletion of CD8+ cells, however, the cytotoxic
      capacity of the remaining T lymphocytes caused death in only 32+/-6% of
      autologous melanoma cells. Blocking of MHC class I, but not class II, molecules
      on hybridomas impaired T cell proliferation, secretion of Th-1-associated
      cytokines, as well as the cytotoxic activity of primed T cells. These findings
      strongly suggest that hybridomas deliver melanoma-associated antigens via MHC
      class I molecules to T lymphocytes, resulting in the generation of CD8+ cytotoxic
      T lymphocytes with effective anti-melanoma activity in vitro. The data may serve
      as a basis for the use of hybridomas in the immunotherapy of malignant melanoma
      in vivo.

PMID- 11570585
TI  - Impact of aging on immune modulation by tumor.
AB  - Tumor development and aging can each alter immune competence. The present study
      aimed to determine the impact of Lewis lung carcinoma (LLC) presence on immune
      parameters of middle-aged (averaging 6.5 months) versus aged (averaging 21.3
      months) mice. An age-associated decline in the CD4+ cell frequency was seen in
      freshly isolated spleen and lymph node cells, as well as in cultures stimulated
      with immobilized anti-CD3. This decline was not further exacerbated by tumor
      presence. What was prominently inhibited by tumor was the capacity of either
      splenic or lymph node CD4+ cells to become stimulated to express IFN-gamma.
      Spleen and lymph node cultures from aged tumor-bearing mice had the lowest
      frequency of CD4+IFN-gamma+ cells and the least amount of secreted IFN-gamma.
      CD8+ cells were not affected by aging, but tumor presence reduced the induction
      of CD8+IFN-gamma+ cells in lymph node cultures. We previously showed that LLC
      growth stimulates myelopoiesis, as seen by splenomegaly and the mobilization of
      immune inhibitory CD34+ progenitor cells. Tumor presence in middle-aged mice
      reduced spleen cell blastogenesis, which was mediated by CD34+ cells. Aged mice
      had reduced blastogenesis, and this was further reduced by presence of tumor.
      However, neither the age-associated immune dysfunction nor the tumor-induced
      immune suppression in aged mice was due to CD34+ progenitor cells. These studies
      show how tumor presence can further compromise the immune dysfunction that
      accompanies aging. In addition, they show that aging impacts on the mechanisms by
      which tumors inhibit T-cell capabilities, with myelopoiesis-associated CD34+
      cells mediating the immune depression of middle-aged tumor-bearers and an
      independent mechanism being responsible for the immune depression in aged tumor
      bearing mice.

PMID- 11570586
TI  - The generation of anti-tumoral cells using dentritic cells from the peripheral
      bloood of patients with malignant brain tumors.
AB  - Dendritic cells (DCs) can be the principal initiators of antigen-specific immune
      responses. We analyzed the in vitro-responses against brain tumor cells using DCs
      from the peripheral blood of patients with brain tumors. Peripheral blood
      mononuclear cells (PBMC) were obtained from 19 patients with malignant brain
      tumors: 12 metastatic brain tumors of lung adenocarcinoma, 7 high-grade
      astrocytomas. PBMC were cultured with 100 ng/ml of GM-CSF and 10 ng/ml of IL-4
      for 5 7 days in order to produce mature DCs. The autologous tumor lysate (5
      mg/ml, containing 1 x 10(6) cells) was then added to the cultured DCs. Using the
      DCs generated by these treatments, we assessed the changes that occurred in their
      immune responses against brain tumor via 51Cr-release and lymphocyte
      proliferation assays. We found that the matured DCs displayed the typical surface
      phenotype of CD3+, CD45+, CD80+ and CD86+. After the pulsation treatment with
      tumor lysate, DCs were found to have strong cytotoxic T lymphocyte activity,
      showing 42.5+12.7% killing of autologous tumor cells. We also found an
      enhancement of allogeneic T cell proliferation after pulsing the DC with tumor
      lysate. These data support the efficacy of DC-based immunotherapy for patients
      with malignant brain tumors.

PMID- 11570587
TI  - Interleukin-10 in serous ovarian carcinoma cell lines.
AB  - Interleukin-10, one of the most potent antiinflammatory cytokines, is expressed
      in ovarian carcinomas in vivo. In contrast to the high levels of IL-10 in ascites
      and tumour tissue, the expression of this cytokine appears to be a rare event in
      ovarian carcinoma cell lines in vitro. Virtually nothing is known about the
      regulation of IL-10 expression in ovarian carcinoma cell lines. We investigated
      the expression of IL-10 in four cell lines originally derived from ovarian serous
      adenocarcinoma: OVCAR-3, SKOV-3, CAOV-3 and OAW-42. IL-10- specific mRNA was
      detected in OVCAR-3 and only this cell line produced IL-10 constitutively under
      serum-free conditions as well as in serum-containing medium. Our studies on the
      regulation of IL-10 secretion in OVCAR-3 revealed that (1) proinflammatory
      stimuli IL-1beta and TNF-alpha, but not LPS, enhance IL-10 secretion, (2) IL-6
      has no influence on the release of IL-10, (3) prostaglandin E2 influences neither
      the spontaneous nor the TNF-alpha- or IL-1beta-stimulated IL-10 production and
      (4) interferon-gamma inhibits IL-10 secretion. We conclude that only a minority
      of serous ovarian carcinoma cells maintain the ability to produce IL-10 in vitro.
      Our data on the regulation of IL-10 production in OVCAR-3 indicate that ovarian
      carcinoma cells share some, but not all, of the regulatory features typical for
      the monocytic IL-10 secretion.

PMID- 11570588
TI  - Inverse bifurcation problem, singular Wiener-Hopf equations, and mathematical
      models in ecology.
AB  - A single-species population dynamics with dispersal in a spatially heterogeneous
      environment is modeled by a nonlinear reaction-diffusion equation with a
      potential term. To each nonlinear kinetics there corresponds a bifurcation curve
      that describes the relation between the growth rate and the central density of a
      steady-state population distribution. Our main concern is an inverse problem for
      this correspondence. The existence of nonlinear kinetics realizing a prescribed
      bifurcation curve is established. It is shown that the freedom of such kinetics
      is of degree finite and even, depending only on the heterogeneity of the
      environment, and conversely that any nonnegative even integer occurs as the
      degree of freedom in some environments. A discussion is also made on under what
      kind of environment the degree is equal to zero or is positive. The mathematical
      analysis involves the development of a general theory for singular multiplicative
      Wiener-Hopf integral equations.

PMID- 11570589
TI  - Allometric scaling in animals and plants.
AB  - In this paper we give a derivation for the allometric scaling relation between
      the metabolic rate and the mass of animals and plants. We show that the
      characteristic scaling exponent of 3/4 occurring in this relation is a result of
      the distribution of sources and sinks within the living organism. We further
      introduce a principle of least mass and discuss the kind of flows that arise from
      it.

PMID- 11570590
TI  - On the formulation and analysis of general deterministic structured population
      models. II. Nonlinear theory.
AB  - This paper is as much about a certain modelling methodology, as it is about the
      constructive definition of future population states from a description of
      individual behaviour and an initial population state. The key idea is to build a
      nonlinear model in two steps, by explicitly introducing the environmental
      condition via the requirement that individuals are independent from one another
      (and hence equations are linear) when this condition is prescribed as a function
      of time. A linear physiologically structured population model is defined by two
      rules, one for reproduction and one for development and survival, both depending
      on the initial individual state and the prevailing environmental condition. In
      Part I we showed how one can constructively define future population state
      operators from these two ingredients. A nonlinear model is a linear model
      together with a feedback law that describes how the environmental condition at
      any particular time depends on the population size and composition at that time.
      When applied to the solution of the linear problem, the feedback law yields a
      fixed point problem. This we solve constructively by means of the contraction
      mapping principle, for any given initial population state. Using subsequently
      this fixed point as input in the linear population model, we obtain a population
      semiflow. We then say that we solved the nonlinear problem.

PMID- 11570591
TI  - Transport functions of riboflavin carriers in the rat small intestine and colon:
      site difference and effects of tricyclic-type drugs.
AB  - The present study was aimed at kinetically characterizing the newly found carrier
      mediated riboflavin transport system in the rat colon, comparing it with that in
      the small intestine, and also probing the potential roles of these transport
      systems in intestinal drug absorption. Riboflavin transport, evaluated by
      measuring the initial uptake into everted intestinal tissue sacs, was saturable
      with a Michaelis constant (Km) of 0.13 microM and a maximum transport rate (Jmax)
      of 0.74 pmol/min/100 mg wet tissue weight (wtw) in the colon. Both the Km and the
      Jmax were smaller than those (0.57 microM and 4.26 pmol/min/100 mg wtw,
      respectively) in the small intestine, suggesting that the transport system in the
      colon has a higher affinity to substrates and a smaller transport capacity than
      its counterpart in the small intestine. The carrier-mediated riboflavin transport
      in the colon, similarly to that in the small intestine, was Na+-dependent and
      inhibited by lumiflavin, a riboflavin analogue with an isoalloxazine ring, but
      not by D-ribose, which forms the side-chain attached to the isoalloxazine ring in
      riboflavin. To further clarify the substrate specificities of the transport
      systems, we examined the effects of several drugs with a tricyclic structure
      similar to isoalloxazine ring on riboflavin transport. Chlorpromazine, a
      phenothiazine derivative, was found to inhibit riboflavin transport in both the
      small intestine and the colon. Methylene blue also was found to be a potent
      inhibitor in both sites. These results suggest that some tricyclic-type drugs
      could interfere with intestinal riboflavin absorption by specific carrier
      mediated transport systems. These transport systems may play roles in the
      absorption of tricyclic-type drugs.

PMID- 11570592
TI  - Altered pharmacokinetics and liver targetability of methotrexate by conjugation
      with lactosylated albumins.
AB  - To enhance the liver targetability, methotrexate (MTX) was conjugated with
      albumin previously substituted with varying content of lactose (L0, L5, and L24).
      The uptake of MTX by rat hepatocytes in vitro increased according to the increase
      in the lactose content on the albumin conjugates. The MTX level in the plasma and
      various organs was determined by counting the radioactivity of [3H]MTX and by
      HPLC assay, separately, to monitor the in vivo fate of MTX not only as total,
      regardless of forms of MTX, but also as free/intact MTX level. Conjugation of MTX
      with albumin alone provided the enhanced delivery of MTX to the liver,
      accompanied by decreased accumulation in the kidney, but by increased
      accumulation in other nontarget organs such lung, heart, and spleen.
      Lactosylation of albumin conjugates further enhanced the delivery of MTX to the
      liver in a lactose content-dependent manner, accompanied by decreased
      accumulation of MTX in the lung and heart as well as kidney. The total MTX level
      accumulated in the liver was 2.9-, 4.1-, and 11.0-fold higher at 1 h and 5.4-,
      7.0-, and 16.5-fold higher at 4 h after injection of MTX-L0, L5, L24 albumin
      conjugates compared with MTX alone. MTX conjugates with lactosylated albumin
      provided low but prolonged level of free/intact MTX in the liver. Taken together,
      the pharmacokinetics and liver targetability of MTX could be favorably modulated
      by controlling the lactose content on the albumin conjugates. Lactosylated
      albumin conjugation might also provide prolonged and targeted delivery of other
      drugs for the treatment of liver diseases.

PMID- 11570593
TI  - Preparation and in vitro evaluation of heparin-loaded polymeric nanoparticles.
AB  - Nanoparticles of a highly soluble macromolecular drug, heparin, were formulated
      with two biodegradable polymers (poly-E-caprolactone [PCL] and poly (D, L-lactic
      co-glycolic-acid) 50/50 [PLAGA]) and two nonbiodegradable positively charged
      polymers (Eudragit RS and RL) by the double emulsion and solvent evaporation
      method, using a high-pressure homogenization device. The encapsulation efficiency
      and heparin release profiles were studied as a function of the type of polymers
      employed (alone or in combination) and the concentration of heparin. Optimal
      encapsulation efficiency was observed when 5000 IU of heparin were incorporated
      in the first emulsion. High drug entrapment efficiency was observed in both
      Eudragit RS and RL nanoparticles (60% and 98%, respectively), compared with PLAGA
      and PCL nanoparticles (<14%). The use of the two types of Eudragit in combination
      with PCL and PLAGA increased the encapsulation efficiency compared with these two
      biodegradable polymers used alone; however, the in vitro drug release was not
      modified and remained low. On the other hand, the addition of esterase to the
      dissolution medium resulted in a significant increase in heparin release. The in
      vitro biological activity of released heparin, evaluated by measuring the anti-Xa
      activity by a colorimetric assay, was conserved after the encapsulation process.

PMID- 11570594
TI  - Preparation by spray drying of amphotericin B-phospholipid composite particles
      and their anticellular activity.
AB  - As a potent drug carrier for systemic fungal infections, amphotericin B(AmB)
      phospholipid composite particles (APCPs) were prepared by the spray drying
      method. AmB and egg phosphatidylcholine, co-dissolved in methanol (0.0425-0.45 mg
      AmB/ml, 0.17-1.8 mg lipid/ml), was nebulized at 2 ml/min. The aerosol produced
      was carried by air at 1000 ml/min to the inner tubes of a serially connected
      distilling column system, of which the outer tubes were supplied with circulating
      water of 95 degrees C. The particles, by scanning electron microphotography, are
      spherical and submicronsized. Upon hydration of the particles in phosphate
      buffered saline for 30 min at room temperature, liposome-like bilayer vesicles
      were formed along with AmB-phospholipid complexes, evidenced by the transmission
      electron microphotographs and the positive peak around 330 nm of the circular
      dichroism spectrum, respectively. The hemolytic abilities of the APCPs were lower
      than those of free drug, without loss of the antifungal activity. The suppressed
      hemolysis could be ascribed to the liposomes and to the complexes that are
      reconstituted by hydration of APCPs. The dry composite particles could circumvent
      the inherent instability of liposomal formulations.

PMID- 11570595
TI  - A comparative study of controlled release matrix tablets of diclofenac sodium,
      ciprofloxacin hydrochloride, and theophylline.
AB  - The need for controlled release formulations for diclofenac sodium,
      ciprofloxacin, and theophylline is well recognized. In our study, controlled
      release tablets of the three drugs were formulated by the matrix-embedding
      technique using ethyl cellulose as retardant. Tablets of all the drugs were of
      good physical quality with respect to appearance, drug content uniformity,
      hardness, weight variation, and friability. In vitro release rate studies showed
      that ethyl cellulose extended the release of the three drugs to 12 hr or more.
      Release patterns from formulations of the three drugs followed Higuchi's square
      root kinetics. At pH 6.8, the release rate was higher in all three drugs,
      probably due to increased solubility of the drugs and/or increased swelling of
      ethyl cellulose at the higher pH. The formulations were highly stable and
      possessed reproducible release kinetics across batches.

PMID- 11570596
TI  - A stability test of liposome preparations using steady-state fluorescent
      measurements.
AB  - The stability of liposome preparations under the action of the nonionic detergent
      Triton X-100 was measured using the fluorescent molecular probe
      octadecylrhodamine B (R18). The probe inserted in the lipid bilayer shows a self
      quenched fluorescence and the degree of quenching depends both on the probe
      concentration and the phase state of the lipid membrane. The addition of
      detergent to the liposomes produces a steep decrease in self-quenching caused by
      dilution of the probe in the bilayer. The curves of steady-state fluorescence
      intensity show an abrupt change in slope that corresponds to the point at which
      liposomes break down into lipid-detergent mixed entities that are different from
      the earlier liposome-monodisperse population. The lytic process was followed in
      parallel by dynamic light scattering (DLS), and the analysis of the DLS results
      agree with the interpretation of the fluorescence measurements. The probe R18
      therefore is a useful marker to test the stability of liposome preparations. The
      advantages of the present method are discussed by comparison with other
      techniques.

PMID- 11570597
TI  - Design and evaluation of buccal adhesive hydrocortisone acetate (HCA) tablets.
AB  - Many studies have shown that topical buccal therapy with steroid anti
      inflammatory drugs is useful in controlling ulcerative and inflammatory mucosal
      diseases. This local treatment is based on the concept that a high activity of
      steroids can be produced at the site of administration and, at the same time, the
      degree of systemic side effects can be minimized or avoided. In this study we
      developed a new formulation consisting of a mucoadhesive tablet formulation for
      buccal administration of hydrocortisone acetate (HCA). Three types of tablet were
      developed containing three mucoadhesive components: hydroxypropylmethyl cellulose
      (Methocel K4M), carboxyvinyl polymer (Carbopol 974P), and polycarbophyl (Noveon
      AA1); the first polymer is a cellulose derivative, the others are both
      polyacrylic acid derivatives. For each of those, three tablet batches were
      produced changing the quantity of the mucoadhesive component (10, 20, and 30%),
      resulting in 9 different formulations. The compatibility of HCA with all
      excipients using Differential Scanning Calorimetry (DSC) was assessed. Tablets
      were manufactured by wet granulation followed by compression. Technological
      controls on granulates (Hausner index, Carr index, granulometry and Karl-Fischer
      percentage humidity) and tablets (thickness, diameter, friability, hardness,
      uniformity of content, weigh uniformity and dissolution kinetic) were carried
      out. Mucoadhesion properties, ex vivo permeability through porcine buccal mucosa,
      in vivo behavior and compliance were evaluated. Technological controls have
      demonstrated that the increase in the (percentage) of mucoadhesive causes an
      increase in granulometry followed by a reduction in the granulate flowability,
      however all the tablets have given satisfactory technological results and
      conformed to the 3rd Ed. European Pharmacopoeia specifications. Mucoadhesion, ex
      vivo permeability and in vivo behavior results notably differed among tablets,
      depending on the quality and quantity of the mucoadhesive component. An overall
      comparison of results showed the tablets containing Carbopol 20% resulted to be
      the best formulation among those developed.

PMID- 11570598
TI  - Effect of pH on diclofenac release from Eudragit RS100 microparticles. A kinetic
      study by DSC.
AB  - The present work is aimed at investigating the release of Diclofenac (DCF) from
      Eudragit RS100 (RS) microparticles to a biological model membrane consisting of
      dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV). The
      microparticles were prepared by the Quasi-Emulsion Solvent Diffusion method
      (QESD). The drug release was monitored by Differential Scanning Calorimetry (DSC)
      technique, following the effects exerted by DCF on the thermotropic behaviour of
      DMPC multilamellar vesicles at different temperatures. DCF affects the transition
      temperature (Tm) of phospholipid vesicles, causing a shift towards lower values,
      which is modulated by the drug fraction entering into the lipid bilayer.
      Calorimetric measurements were performed at two different pH (4.0 and 7.4) on
      suspensions of blank liposomes added to weighed amounts of unloaded and DCF
      loaded microspheres, as well as to the powdered free drug, after incubation at 37
      degrees C. The Tm shifts, caused by the drug released from the polymeric system
      or by the free drug during incubation cycles, were compared to those caused by a
      chosen molar fractions of the free drug dispersed directly in the membrane. This
      in vitro study suggests as the kinetic process involved in drug release is
      influenced by the amount of drug loaded in the microspheres as well as by the pH
      value, acting on drug solubility and membrane disorder.

PMID- 11570599
TI  - Carotid sinus "irritability" rather than hypersensitivity: a new name for an old
      syndrome?
AB  - Carotid sinus hypersensitivity (CSH) is a well-described cause of syncope,
      resulting in bradycardia and/or hypotension in response to neck pressure. The
      authors hypothesized that (CSH) represents an inappropriate response of the
      baroreflex system to a nonphysiologic stimulus, rather than a truly
      hypersensitive carotid sinus (ie, excessive vagotonia and sympathoinhibition in
      response to arterial hypertension). To test their hypothesis, the authors used a
      neck chamber to deliver stepped, R-wave-triggered changes in transmural carotid
      sinus pressure, from +40 to -60 mm Hg, during a single held expiration. The
      authors studied 7 men (age 69 +/- 8y; mean age +/- SD) with carotid sinus
      syndrome and 10 age- and sex-matched controls. Seven repetitions of pressure
      changes were averaged, and the carotid sinus response described by changes in the
      R-R interval. There was no statistical difference in carotid-cardiac baroreflex
      gain (R-R interval/pressure change; mean gain +/- SD, 3.0 +/- 2.1 msec/mm Hg and
      2.2 +/- 3.0 msec/mm Hg, respectively) or other markers of carotid baroreflex
      responses between the subjects and controls. These preliminary results suggest
      that (CSH) may not be a "hypersensitive" reflex, but rather an inappropriate
      response, or "irritability," of the baroreflex system to nonphysiologic
      deformation of the carotid sinus and/or surrounding tissues.

PMID- 11570600
TI  - Phenotypic and neuropathologic heterogeneity of anti-Hu antibody-related
      paraneoplastic syndrome presenting with progressive dysautonomia: report of two
      cases.
AB  - The anti-Hu antibody (HuAb) is directed against RNA-associated neuronal proteins
      and is known to cause paraneoplastic encephalomyelitis/sensory neuronopathy
      syndrome mostly when associated with small cell lung cancer (SCLC).
      Paraneoplastic encephalomyelitis/sensory neuronopathy syndrome with concurrent
      autonomic neuropathy has been reported to occur in paraneoplastic syndromes,
      although its occurrence concomitant with acute pandysautonomia is less frequent.
      The authors describe the clinical, neuropathologic, and serologic features of two
      cases with an anti-Hu-related paraneoplastic syndrome presenting with progressive
      autonomic neuropathy. Both patients showed features of dysautonomia, including
      postural dizziness, abdominal pain, and diarrhea, and symptoms of sensory
      neuropathy. Investigations disclosed severe sensory and autonomic neuropathy and
      positive HuAb titers. The disease of patient 1 had a very rapid progression, and
      the patient died of cardiac arrest within 2 months of the onset of symptoms. The
      autopsy revealed SCLC. In contrast, the disease of patient 2 had a less
      aggressive course. An extensive tumor search disclosed SCLC only 28 months after
      onset of symptoms, and the patient died 1 month later of cardiorespiratory
      arrest. Autopsies in both cases showed inflammation involving the
      intermediolateral columns and the dorsal root ganglia. These two cases illustrate
      the association of early dysautonomia with HuAb-related paraneoplastic syndrome
      and the variations of clinical, neuropathologic, and serologic findings in these
      types of cases.

PMID- 11570601
TI  - Peripheral neuropathy as the presenting feature of multiple system atrophy.
AB  - The authors report a case of multiple system atrophy (MSA) with an onset as a
      peripheral nerve involvement. Their patient, a 55-year-old man, had a 3-year
      history of distal weakness and atrophy in upper limbs with dysesthesia in the
      feet. Other identifiable causes of peripheral neuropathy were ruled out. The
      authors postulate that peripheral nervous system impairment can anticipate the
      typical appearance of MSA, and they suggest that, in peripheral neuropathies with
      autonomic system dysfunction, after excluding main causes of autonomic
      neuropathy, MSA may need to be suspected.

PMID- 11570602
TI  - Polymorphisms 'r us.

PMID- 11570603
TI  - Obesity and autonomic function.

PMID- 11570604
TI  - Is peripheral neuropathy a feature of multiple system atrophy?

PMID- 11570605
TI  - The riddles of heart rate variability.

PMID- 11570606
TI  - Genetic polymorphisms of adrenergic receptors.
AB  - Recent advances in molecular biology have enhanced the understanding of
      adrenergic receptors. They have allowed the characterization of the several
      subtypes of adrenergic receptors expressed and have expanded the research about
      the potential physiologic functions they mediate. Furthermore, variant forms, or
      polymorphims, of the genes that code for these receptors are being identified.
      These genetic variants may or may not result in functional differences in the
      receptors they encode. There is obvious interest in determining the physiologic
      and clinical relevance of these polymorphisms. The purpose of this review is to
      describe these polymorphisms and the often contradictory literature pertaining to
      their clinical significance. Progress in this area is being made at a rapid pace.
      As the allele-disease relations become less equivocal, it might be possible to
      predict individual differences in susceptibility to a disease, disease prognosis,
      and response to treatment.

PMID- 11570607
TI  - Impaired autonomic control of heart rate and blood pressure in obesity: role of
      age and of insulin-resistance.
AB  - The objectives of this study were to investigate cardiac and peripheral autonomic
      nervous system changes in normotensive overweight or obese subjects and the
      possible relation between these changes and insulin resistance independent of
      age. The authors used spectral analysis to measure simultaneously the short-term
      variability of heart rate (HR) and blood pressure (BP) using a Finapres device,
      in 67 normotensive overweight or obese patients (age 37 +/- 12 y, body mass index
      [BMI] = 37 +/- 9 kg/m2) and 45 never-obese subjects (controls; age 41 +/- 13 y,
      BMI 22 +/- 2 kg/m2). The spectral density was determined in three situations:
      subjects in the supine position, spontaneously breathing; subjects in the supine
      with controlled breathing; and subjects standing. The insulin sensitivity of
      overweight and obese subjects was determined from homeostatic model assessment
      (HOMA). The variability of normalized low-frequency (LF) spectral analysis of
      both HR and BP was lower in overweight or obese subjects than in controls, in the
      supine and standing positions (p <0.01). Normalized LF spectral analysis was
      negatively correlated to BMI independent of age, whatever the position.
      Homeostatic model assessment values were negatively correlated to the normalized
      LF spectral of HR, systolic BP and diastolic BP, in the standing position
      independent of BMI and age (p <0.05). Normalized high frequency (HF) of HR during
      controlled breathing decreased with age but not with BMI. In normotensive
      overweight or obese subjects, changes in sympathetic nervous system modulation
      are strongly correlated to insulin resistance. Decreased HR and BP variability
      could partly account for the higher cardiovascular risk and incidence of sudden
      death in obese persons.

PMID- 11570608
TI  - Heart rate variability in childhood obesity.
AB  - Obesity is characterized by hemodynamic and metabolic alterations. Autonomic
      control on cardiac function involvement is controversial. The aim of the study
      was to assess early sign of cardiac autonomic dysfunction in obesity, using time-
      and frequency-domain heart rate variability (HRV) analysis in a pediatric
      population. METHODS: 32 obese children (OB) (17 M, 15 F; 13.9 +/- 1.7 y) were
      compared with 13 healthy lean subjects (7 M, 6 F; 12.9 +/- 1.6 y). For each
      participant, the authors performed a clinical examination, laboratory testing,
      blood pressure (BP) measurements, and 24-hour electrocardiograph/ambulatory BP
      monitoring. The spectral power was quantified in total power, low-frequency (LF)
      power, index of sympathetic tone, high-frequency (HF) power, index of vagal tone,
      and LF/HF ratio. Low frequency and HF were averaged to obtain 3 measures: 24
      hour, daytime, and nighttime levels. Total, long-term, and short-term time-domain
      HRV values were calculated. RESULTS: The obese children had higher casual and
      ambulatory BP, and higher fasting glucose, insulin, and triglyceride levels.
      Overall HRV values were not significantly lower in OB. The obese children had
      significantly lower 24-hour and nighttime high-frequency normalized units, and
      time-domain measures of vagal activity. Low-frequency power showed an inverse but
      not significant pattern. The OB group had significantly greater 24-hour and
      nighttime LF/HF ratios. CONCLUSIONS: The authors found an increase in heart rate
      and in BP associated with parasympathetic heart rate control decrease in
      stabilized obese normotensive children.

PMID- 11570609
TI  - Facilitating laser Doppler measurements of cutaneous adrenergic vasoconstriction:
      a comparison of methods.
AB  - Detecting vasoconstriction in the skin of the human forearm is often difficult
      because cutaneous perfusion is usually low, even in the absence of
      vasoconstrictive agents. However, flow through "vasoconstricted" skin can be
      detected by increasing the background skin blood flow. The aim of the current
      study was to evaluate local warming and postocdusive reactive hyperemia as
      techniques for increasing background flow to facilitate laser Doppler
      measurements of cutaneous vasoconstriction in the forearm. Noradrenaline
      introduced by iontophoresis into the forearm of healthy volunteers initially
      reduced the peak hyperemic response (mean decrease in hyperemia 21 +/- 7%, p
      <0.01), compared with a saline control. However, vasoconstriction was unrelated
      to the dose of noradrenaline and was not detectable when the test was repeated,
      possibly because the peak of the normal hyperemic response decreased with
      repeated occlusions. When the forearm was warmed to 42 degrees C, noradrenaline
      introduced by iontophoresis produced dose-dependent vasoconstriction relative to
      saline control sites and skin not having undergone iontophoresis (greatest mean
      decrease 64 +/- 7%, p <0.001). Therefore, local warming is recommended over
      reactive hyperemia for facilitating laser Doppler recordings of cutaneous
      vasoconstriction in the human forearm.

PMID- 11570611
TI  - Daycare centers: are indoor allergen levels important?

PMID- 11570610
TI  - Standardized tests of heart rate variability: normal ranges obtained from 309
      healthy humans, and effects of age, gender, and heart rate.
AB  - The authors undertook this study to determine the effects of age, gender, and
      heart rate (HR) on the results of cardiac autonomic function tests for measuring
      heart rate variability (HRV) in a large sample of healthy subjects (n = 309).
      Conventional tests (deep breathing, maximum/minimum 30:15 ratio), and a
      standardized 5-minute resting study, including spectral analysis of HR, were
      used. The main findings included (1) the indices of all tests, except for the
      ratio of the low- (LF) to high-frequency (HF) spectral power (LF/HF ratio) and HR
      itself, are inversely related to age in both sexes; (2) the 5-minute spectral
      bands (except for the LF/HF ratio), the variation coefficient, expiratory
      inspiratory ratio during deep breathing, and the maximum/minimum 30:15 ratio are
      independent of HR; (3) women up to the age of 55 years have a higher resting HR
      compared with men; (4) young and middle-aged women show a significantly lower LF
      power and LF/HF ratio compared with age-matched men, whereas no significant
      gender differences are observed in the absolute HF power. The authors computed
      age- and gender-dependent normal values for each of the HRV indices studied here
      and discuss the clinical consequences arising from gender differences in HRV.

PMID- 11570612
TI  - Classification of allergic and pseudoallergic reactions to drugs that inhibit
      cyclooxygenase enzymes.

PMID- 11570613
TI  - A superantigen hypothesis for the pathogenesis of chronic hypertrophic
      rhinosinusitis, allergic fungal sinusitis, and related disorders.
AB  - BACKGROUND: Chronic eosinophilic-lymphocytic respiratory mucosal inflammatory
      disorders include hypertrophic sinus disease, allergic fungal sinusitis, allergic
      bronchopulmonary aspergillosis, and chronic severe asthma. They have many
      analogous or shared aspects of pathology at molecular, cellular, and clinical
      levels of analysis. OBJECTIVE: To propose a theory, and supporting data through
      comprehensive literature review, that unifies these diseases' pathogenesis.
      METHODS AND DATA SOURCES: Current medical literature was used as supportive
      background information. Reinterpretation of existing studies and reasoned
      speculation were used when necessary and identified where used. English language
      MEDLINE articles that referenced sinusitis, rhinosinusitis, allergic fungal
      sinusitis, asthma, allergic bronchopulmonary aspergillosis, nasal polyp,
      superantigen, and T cell receptor from 1983 to present were potentially used as
      background or supportive information. Additional referenced articles, published
      abstracts, and National Center for Biotechnology Information Entrez protein
      database searches were used. Case reports, studies, review articles, and
      textbooks were included. RESULTS: Multiple lines of evidence support the proposed
      hypothesis that microbial T cell superantigen production, persistence, and host
      responsiveness are the fundamental components that unify the pathogenesis of all
      common chronic eosinophilic-lymphocytic respiratory mucosal inflammatory
      disorders. Superantigen amplification of preexisting immunopathology is the
      proposed mechanism for disease induction and maintenance. Preexisting
      immunopathology is created in the individual by a potential heterogeneity of
      immunopathologic signals that can include type I immediate hypersensitivity,
      other antigen-specific immune responses, cytokine dysregulation, eicosanoid
      dysregulation, various genetic mutations, and other molecular pathology. Although
      the ability to develop chronic severe inflammatory disease is dependent upon this
      immunopathology, host T cell receptor V beta genetics and persistent superantigen
      production/exposure at the respiratory mucosa by relevant superantigen-producing
      extra- or intracellular microbes are postulated to be required. This mechanism
      for disease pathogenesis may also apply to other disorders. Approaches to prove
      this theory and its predictions are presented. CONCLUSIONS: The pathogenesis of
      all the disorders discussed can be unified through the superantigen hypothesis
      proposed. Multiple lines of evidence support this hypothesis. How we view these
      common conditions will change, and new research into pathogenesis and treatment
      will occur if this proves true.

PMID- 11570614
TI  - House dust mite, cat, and cockroach allergen concentrations in daycare centers in
      Tampa, Florida.
AB  - BACKGROUND: Allergen exposure in early childhood is a risk factor for
      sensitization and the development of asthma. Studies performed in Europe, New
      Zealand, and Singapore indicated the presence of indoor allergens in childcare
      centers and schools. However, the importance of indoor allergens in daycare
      centers in humid and warm regions of the world is not known. OBJECTIVE: To
      measure total mite counts, Der p 1, Der f 1, Fel d 1, and Per a 1 allergens in
      dust samples and mite allergen airborne concentrations in daycare centers in
      Tampa, Florida, United States. METHODS: Twenty daycare centers were surveyed for
      mite, cat, and cockroach allergens in Tampa, FL. One dust and two air samples
      (one during the day and one during the night) were collected in each center. Dust
      samples were extracted and analyzed for mite (Der p 1 and Der f 1), cat (Fel d
      1), and cockroach (Per a 1) allergens. Mite airborne allergen concentrations were
      analyzed by RAST inhibition and expressed in standardized mite allergen units per
      m3 of air (AU/m3). RESULTS: Mites were identified in 15 samples, and
      concentrations ranged from 10 to 1,200 mites/g (298 +/- 355.2). The most
      prevalent mite species was Dermatophagoides pteronyssinus ( Der p 1). Der p 1
      and/or Der f 1 were detected in 10 daycare centers. Der p 1 was detected in eight
      centers and ranged from I to 21.8 microg/g of dust (5.4 +/- 6.9); Der f 1 was
      detected in 3 centers and ranged from 0.2 to 2.1 microg/g of dust (1.3 +/- 0.9).
      Per a 1 and Fel d 1 were detected in all centers in small quantities; Per a 1
      ranged from 8 to 1,806 ng/g (263.1 +/- 449.7) and Fel d 1 from 0.2 to 120 U/g of
      dust (16.6 +/- 31.7), respectively. Airborne mite allergen was detected in 18
      centers and ranged from 0.01 to 2.7 AU/m3 during the day (0.2 +/- 0.6) and from
      0.01 to 0.12 AU/m3 during the night (0.06 +/- 0.03), P = 0.001. CONCLUSIONS:
      Mite, cat, and cockroach allergens are present in daycare centers in Tampa, FL.
      Mite allergen concentrations exceeded levels that have been associated with
      sensitization and symptoms in allergic subjects in 40% of these centers.

PMID- 11570615
TI  - Tolerability to new COX-2 inhibitors in NSAID-sensitive patients with cutaneous
      reactions.
AB  - BACKGROUND: The safety of new anti-inflammatory drugs in patients intolerant to
      classic cyclooxygenase (COX) inhibitors with urticaria and angioedema has not
      been determined. OBJECTIVES: To investigate the clinical tolerance to COX-2
      inhibitors in patients with cutaneous symptoms attributable to classic
      nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: Patients with urticaria
      or angioedema triggered by NSAIDs were challenged with COX-2 inhibitors by the
      single-blinded, placebo-controlled oral method. RESULTS: One hundred ten NSAID
      sensitive patients were submitted to 184 oral challenges with COX-2 inhibitors.
      Eighty-two patients (74.5%) were cross-reactors and 28 patients (25.4%) were
      single reactors. Reaction rates for COX-2 inhibitors were 21.3% for nimesulide,
      17.3% for meloxicam, 33.3% for celecoxib, and 3.0% for rofecoxib. CONCLUSIONS:
      Some COX-2 inhibitors, such as rofecoxib, are relatively safe in NSAID-sensitive
      patients with urticaria or angioedema. However, the tolerance profile varies with
      the drug, which might be related to a differential selectivity of the drug for
      COX-1 and COX-2. COX-1 inhibition would represent a major mechanism for cutaneous
      adverse reactions to NSAIDs. Controlled oral provocation with new NSAIDs is
      useful for the proper management of patients sensitive to classic NSAIDs
      requiring analgesic and anti-inflammatory treatment.

PMID- 11570616
TI  - The impact of depressive symptoms on the functional status of inner-city patients
      with asthma.
AB  - BACKGROUND: Functional deficits are common in patients with asthma. If there is
      cooccurring depression, these deficits may be more severe and/or more persistent.
      OBJECTIVE: This study was undertaken to determine 1) the prevalence and severity
      of depressive symptoms in a sample of inner-city patients being treated for
      asthma and 2) the impact of these symptoms on functional status. METHODS: Three
      hundred seventeen enrollees in an inner-city asthma program were evaluated using
      the health status questionnaire and the Center for Epidemiologic Studies
      Depression Scale (CES-D) at baseline and at 3- and 6-month follow-ups. Two groups
      were created based on patients' CES-D baseline scores, using a commonly used
      cutpoint to define "caseness" for depression. The two groups were compared using
      ANOVA, chi2, and the general linear model for repeated measures. RESULTS: Of the
      sample, 55.01% had a CES-D score greater than the cutpoint for depression. The
      mean was 29.3 +/- 11.95, well above the scores commonly used to indicate the
      presence of depression. The depressed group had lower scores on many measures of
      functional capacity at baseline; whereas both depressed and nondepressed patients
      improved over time on the physical performance measure (the physical performance
      measure subscale of the health status questionnaire), the mean score for the
      depressed group was consistently lower. CONCLUSIONS: The prevalence of depressive
      symptoms was greater than expected. Depression was persistent and had a major
      impact on functional capacity. Routine depression screening may be especially
      important in inner-city patients and other groups thought to be at increased risk
      for poor outcome.

PMID- 11570617
TI  - Effects of zafirlukast upon clinical, physiologic, and inflammatory responses to
      natural cat allergen exposure.
AB  - BACKGROUND: Leukotriene receptor antagonists have been shown to attenuate
      physiologic changes in the upper and lower airways induced by allergen challenge.
      However, it is unknown whether these drugs modulate airway inflammation after
      exposure to allergen in a natural setting. OBJECTIVE: To determine the effects of
      the oral leukotriene receptor antagonist zafirlukast upon symptoms, changes in
      pulmonary function, and indices of inflammation in the upper and lower airways
      induced by natural exposure to cats. METHODS: Zafirlukast, 20 mg twice daily, or
      placebo was administered to 18 cat-allergic asthmatic patients in this
      randomized, double-blind, crossover study. Cat room challenges were performed
      after a 1-week period of each treatment. Upper and lower airway symptoms were
      measured and spirometry performed before and at regular intervals during each
      challenge. Nasal lavage and sputum induction were performed 24 hours before and
      after each challenge. RESULTS: Zafirlukast significantly improved the
      prechallenge baseline FEV1 (P = 0.001) and attenuated the decrease in FEV1
      induced by cat challenge (P = 0.019). Zafirlukast also significantly reduced
      lower airway symptoms associated with cat challenge (P = 0.005) but had no
      effects on nasal symptoms. Although zafirlukast did not significantly differ from
      placebo in its effects on sputum inflammatory cells or eosinophil cationic
      protein, it significantly reduced the absolute counts of total white cells,
      lymphocytes, neutrophils, and basophils in nasal lavage fluid. CONCLUSIONS:
      Zafirlukast, 20 mg twice daily for 1 week, demonstrated a significant protective
      effect on symptoms of asthma and alterations in pulmonary function induced by
      natural cat exposure, whereas nasal symptoms and markers of sputum inflammation
      were not affected by the medication.

PMID- 11570618
TI  - IgE levels are the same in chronic fatigue syndrome (CFS) and control subjects
      when stratified by allergy skin test results and rhinitis types.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) has an uncertain pathogenesis.
      Allergies have been suggested as one cause. OBJECTIVE: The aim of this study was
      to compare serum immunoglobulin (Ig)E in CFS and control subjects to determine
      whether IgE levels were elevated in CFS. This would be suggestive of increased
      atopy in CFS. METHODS: IgE was measured by quantitative ELISA (sandwich)
      immunoassay in 95 CFS and 109 non-CFS control subjects. Subjects were classified
      by positive or negative allergy skin tests (AST) and rhinitis questionnaires
      (rhinitis score, RhSc) into four rhinitis types: nonallergic rhinitis (NAR with
      positive RhSc and negative AST); allergic rhinitis (AR with positive AST and
      RhSc); atopic/no rhinitis (AST positive/RhSc negative); and nonatopic/no rhinitis
      (both AST and RhSc negative) subjects. RESULTS: IgE was not significantly
      different between control (128 +/- 18 IU/mL, mean +/- SEM) and CFS (133 +/- 43
      IU/mL) groups, or between control and CFS groups classified into the four
      rhinitis types. IgE was significantly higher in subjects with positive AST
      whether or not they had positive RhSc or CFS symptoms. CONCLUSIONS: Elevated IgE
      and positive AST indicate allergen sensitization, but are not necessarily
      indicators of symptomatic allergic diseases. There was no association between IgE
      levels and CFS, indicating that atopy was probably not more prevalent in CFS.
      Therefore, TH2-lymphocyte and IgE-mast cell mechanisms are unlikely causes of
      CFS.

PMID- 11570619
TI  - Long-term cetirizine treatment reduces allergic symptoms and drug prescriptions
      in children with mite allergy.
AB  - BACKGROUND: Experimental data demonstrate that mite allergy is characterized by
      persistent chronic inflammation, even during asymptomatic periods. This suggests
      that long-term continuous treatment be included in the global strategy of allergy
      treatment. OBJECTIVE: We conducted a study to evaluate whether regularly
      administered cetirizine reduces allergic symptoms and drug prescriptions in
      children with mite allergy. METHODS: In this double-blind, randomized, placebo
      controlled study, two parallel groups of 10 children with mite allergy (mean age:
      6.5 years) received either cetirizine or placebo daily for 6 months. Participants
      were allowed to take rescue medications for rhinitis and/or mild asthma. The
      symptoms (nasal itching, sneezing, obstruction, rhinorrhea, conjunctival itching,
      lacrimation, conjunctival hyperemia, cough, wheezing, and chest tightness) were
      recorded on a diary card. The intake of cetirizine (as additional symptomatic
      treatment), antibiotics, acetaminophen, beta2-agonists, inhaled and systemic
      corticosteroids was also recorded. RESULTS: Symptom scores and drug consumption
      were significantly lower (P < 0.05) in the cetrizine-treated group versus the
      placebo group. The greatest reductions were in cetirizine itself, inhaled
      corticosteroids, beta2-agonists, and antibiotics. No side effects were reported
      in either group. CONCLUSIONS: In mite-allergic children, cetirizine administered
      daily for prolonged periods decreases symptoms of and drug prescriptions for
      allergic rhinitis and asthma compared with symptomatic treatment.

PMID- 11570620
TI  - A report of a rare immediate reaction after ingestion of acetaminophen.
AB  - BACKGROUND: Acetaminophen hypersensitivity is rare and, when seen, is usually in
      association with sensitivity to nonsteroidal anti-inflammatory drugs. METHODS:
      This is a case report of an immediate reaction to acetaminophen, confirmed by a
      drug challenge, in a subject who tolerated ibuprofen. RESULTS: After an oral
      challenge with 50 mg of acetaminophen, the subject had generalized pruritus,
      urticaria, and dyspnea. CONCLUSIONS: This patient demonstrates a rare but
      potentially severe reaction to acetaminophen that may occur in patients who are
      not otherwise sensitive to other nonsteroidal anti-inflammatory drugs.

PMID- 11570621
TI  - Novel computer-based assessment of asthma strategies in inner-city children.
AB  - BACKGROUND: Childhood asthma continues to be a growing medical concern in the
      United States, affecting > 17 million children in 1998. The mortality rate from
      asthma in children aged 5 to 14 years has nearly doubled, from 1.7 deaths per
      million to 3.2 deaths per million between 1980 and 1993. OBJECTIVE: To evaluate
      the use of artificial neural networks (ANNs) to rate problem-based strategies for
      asthma management in a defined population of children. METHODS: The participants
      in our study were recruited from a local inner-city medical facility in Los
      Angeles. The majority of participants had received the diagnosis of mild-to
      moderate-persistent asthma. Each participant was given 10 asthma-based problems
      and asked to manage them. Each management decision and its order were entered
      into a database. This database was used to train an artificial neural network
      (ANN). The trained ANN was then used to cluster the various performances, and
      outputs were evaluated graphically. RESULTS: Three hundred five performances were
      analyzed through our trained neural network. Our ANN classified five major
      clusters representing different approaches to solving an acute asthma case.
      CONCLUSIONS: ANNs can build rich models of complex phenomena through a training
      and pattern-recognition process. Such networks can solve classification problems
      with ill-defined categories in which the patterns are deeply hidden within the
      data, and models of behavior are not well defined. In our pilot study, we have
      shown that ANNs can be useful in automating evaluation and improving our
      understanding of how children manage their asthma.

PMID- 11570622
TI  - Delayed hypersensitivity to cefazolin: report on a case involving lymphocyte
      transformation studies with different cephalosporins.
AB  - BACKGROUND: A cell-mediated immunopathogenic mechanism has been demonstrated in
      only a few cases of cutaneous reactions to systemically administered
      cephalosporins. OBJECTIVE: The aim was to investigate the pathogenic mechanism of
      a maculopapular rash experienced by a subject during cefazolin therapy. METHODS
      AND RESULTS: Prick, intradermal, and patch tests were carried out using
      penicillin determinants, ampicillin, amoxicillin, cefazolin, cephalothin,
      cefuroxime, ceftazidime, and ceftriaxone. Those tests for penicillin G and its
      determinants, as well as for ampicillin and amoxicillin, were negative. The
      patient displayed patch-test and delayed intradermal-test positivity to all the
      cephalosporins tested. No specific immunoglobulin E antibodies were found for
      penicillins or cefazolin. The lymphocyte-transformation-test results were
      negative for all the penicillins tested and showed a positive concentration
      effect curve for cefazolin, ceftazidime, and ceftriaxone at concentrations up to
      50 microg/mL. At 100 microg/mL the responses decreased with all the
      cephalosporins tested. Challenges with penicillin G and amoxicillin were well
      tolerated, but the challenge with cefazolin was positive. CONCLUSIONS: The data
      of this case demonstrate delayed hypersensitivity to cefazolin. Patch tests and
      delayed-reading intradermal tests can be a simple and effective means of
      diagnosing this type of reaction. Both in vivo and in vitro studies indicate that
      the responses were directed toward a determinant shared by all cephalosporins,
      but not by penicillins. The concentration of the cephalosporins used for the in
      vitro lymphocyte stimulation was critical, because at the concentrations normally
      used to test other beta-lactams the response decreased. This phenomenon may be
      attributable to an immunosuppressive, rather than toxic, effect.

PMID- 11570624
TI  - Giant ragweed.

PMID- 11570623
TI  - IgE-mediated anaphylaxis after first intravenous infusion of cyclosporine.
AB  - BACKGROUND: Intravenous administration of cyclosporine, which contains Cremophor
      EL (a polyethoxylated castor oil; BASF, Berlin, Germany), has occasionally
      resulted in an anaphylactic reaction. An apparent hypersensitivity reaction
      (bronchospasm and decrease in blood pressure) had occurred during heart
      transplantation in a 59-year-old woman after intravenous infusion of
      cyclosporine. Subsequent oral administration of cyclosporine precipitated no
      reaction. OBJECTIVE: The purpose of this study was to attempt to ascertain the
      mechanism responsible for the anaphylactic reaction. METHODS: Hypersensitivity
      investigations, including total serum IgE and allergen-specific IgE
      quantifications, skin testing, and basophil activation tests by flow cytometric
      determination of CD63 upregulation were undertaken in the study patient and in
      two healthy control subjects who were free of medication. RESULTS: The results of
      intradermal testing with Cremophor EL were positive after 15 minutes in the study
      patient only. Both cyclosporine and Cremophor EL induced considerable activation
      of the basophils from our study patient, with an upregulation of CD63 expression
      from 1% to 39% and 55%, respectively. In contrast, the expression of CD63 on
      basophils from the two control subjects remained essentially unchanged.
      CONCLUSIONS: The negative investigative findings in the control subjects, the
      patient's clinical manifestations in temporal relationship to the infusion, her
      positive results on intradermal testing with Cremophor, the basophil activation
      test results, and her uneventful course after oral administration of cyclosporine
      strongly support the presence of IgE antibodies to Cremophor EL in our patient.

PMID- 11570625
TI  - European Academy of Childhood Disability at Goteborg.

PMID- 11570626
TI  - Maternal antecedents for cerebral palsy in extremely preterm babies: a case
      control study.
AB  - The study aimed to identify significant antenatal risk factors for cerebral palsy
      (CP) among extremely preterm infants with a matched case-control design. Infants
      born between 1989 and 1996 at 24 to 27 weeks' gestation who survived to hospital
      discharge were evaluated: 30 with a proven diagnosis of CP at 2 years corrected
      for prematurity and 120 control children matched for gestational age without CP.
      Information on maternal obstetric risk factors and medication was obtained.
      Matched analyses were performed and odds ratios (OR) and 95% confidence intervals
      (CI) were calculated. An antenatal diagnosis of intrauterine growth restriction
      was associated with an increased risk of CP (OR 6.6; 95% CI 1.8 to 25.2), while
      maternal administration of corticosteroids was associated with a reduced risk of
      CP (OR 0.4; 95% CI 0.1 to 0.98). A high rate of placental histopathology was
      achieved but no relation between clinical or histological chorioamnionitis or
      funisitis and CP was demonstrated. Maternal preeclampsia was not associated with
      a statistically significant reduction in the risk of CP. It is concluded that a
      reduced risk of CP in extremely preterm infants is associated with the antenatal
      use of corticosteroids.

PMID- 11570627
TI  - Hip dysplasia in bilateral cerebral palsy: incidence and natural history in
      children aged 18 months to 5 years.
AB  - Children with bilateral cerebral palsy (CP) born during 1989 to 1992 (n=346) to a
      geographically defined population were ascertained and followed up to age 5
      years. The aims of the study were to monitor hip development by serial X-rays; to
      record gross locomotor development, aspects of physical management, and any hip
      related orthotics or surgery; to learn more of the natural history of hip
      development in this condition; and to provide guidelines for a surveillance
      protocol for those clinically managing children with bilateral CP. Children were
      X-rayed at 18, 24, 30, 48, and 60 months. X-rays were taken in a standardized
      position and measured to record migration percentage, acetabular index, Sharp's
      angle, and Smith's diaphyseal ratios. Relationships between the measures were
      investigated and a natural history of the children's hip development suggested.
      At as early as 18 months, migration percentages were significantly greater than
      in the normally developing population, although no measured CP factor could be
      identified to be the cause of this early change. Two possible factors affecting
      early hip development are described, neither of which is clinically apparent: the
      first separates the bilateral CP population as a whole from the normal
      population; but there is an additional presdisposing factor affecting some
      children only which in the presence of the motor disorder, has a significant
      influence on early hip development and subsequent dysplasia. The study confirms
      that, when measured correctly, migration percentage is the best guide to hip
      surveillance and the need for treatment. It is suggested that all children with
      bilateral CP should be X-rayed in a standardized position at 30 months (corrected
      for gestational age).

PMID- 11570628
TI  - Health-related quality of life and functional outcome measures for children with
      cerebral palsy.
AB  - The aim of this study was to examine measures of health-related quality of life
      (HRQL) in children with cerebral palsy (CP) by comparing scores of a generic HRQL
      measure, the Child Health Questionnaire (CHQ); a disease-specific HRQL measure
      for children with CP, the Caregiver Questionnaire (CQ); and a pediatric
      functional measure, the Wee-Functional Independence Measure (WeeFIM).
      Participants included 30 caregivers of children with CP. The caregivers' children
      were a mean age of 8 years 6 months (17 females, 13 males). The ethnic origin of
      the children was 18 African-American, 8 white, 3 Hispanic, and 1 Middle Eastern.
      Significant correlations were found between the CQ and WeeFIM total and subscale
      scores (r=0.388 to 0.641). There was no correlation between the CHQ and CQ total
      summary scores, but significant correlations were found between the CHQ subscales
      related to parent time and family cohesion and the CQ total and subscale scores
      (r=0.386 to 0.481). The lack of correlation between the CHQ and WeeFIM indicates
      HRQL and function are different constructs that cannot be inferred from each
      other. The fair relationship found between the CQ and WeeFIM suggests that the
      constructs measured in these two assessments overlap. The lack of correlation
      between the total summary scores of the CHQ and CQ suggests the CQ may be a more
      specific measure of HRQL for this population that reflects the impact of the
      child's condition on the caregiver.

PMID- 11570629
TI  - Therapeutic electrical stimulation in cerebral palsy: a randomized, controlled,
      crossover trial.
AB  - The aim of this study was to evaluate the effect of therapeutic electrical
      stimulation (TES) applied to antagonists of spastic leg muscles on gross motor
      function in children with spastic diplegic cerebral palsy. Twelve children
      between 5 and 12 years of age completed a 24-month crossover study in which six
      were randomly assigned to receive TES for the first 12 months and the remaining
      six for the last 12 months. Physiotherapy and a home training program were not
      altered. All were evaluated blindly in terms of tests of motor function and video
      recordings at the start and at 12 and 24 months. At the end of the study
      parents/carers gave a subjective assessment of the effect of TES. No significant
      effect of TES on motor or ambulatory function was found on the blinded
      evaluation, but parents of 11 of the 12 children stated that TES had a
      significant effect. We conclude that it is unlikely that TES has a significant
      effect on motor and ambulatory function in spastic diplegia.

PMID- 11570630
TI  - Low levels of insulin-like growth factor-I in cerebrospinal fluid in children
      with autism.
AB  - Autism is a behaviourally defined syndrome characterized by disturbances of
      social interaction and communication and restrictions of behaviour patterns and
      imagination. The pathogenesis of autism is unknown but it is suspected that a
      number of genetic factors may be involved. Neurotrophic factors such as insulin
      like growth factor-I (IGF-I) play a role in early brain development. The aim of
      this study was to determine whether IGF-I levels might be associated with the
      development of autism. IGF-I levels were measured in the CSF of 11 children with
      autism (4 females, 7 males; mean age 3.8 years, SD 1.1) using a sensitive
      radioimmunoassay method and compared with levels in 11 control participants (6
      females, 5 males; mean age 3.8 years). Levels of IGF-I in the CSF were
      statistically significantly lower in the children with autism than in the control
      children (p=0.03). IGF-I may play a role in pathogenetic mechanisms of autism and
      the role of neurotrophic factors in autism and other neurodevelopmental diseases
      should be studied further.

PMID- 11570631
TI  - Williams syndrome and deficiency in visuospatial recognition.
AB  - This study aimed to assess the visuospatial abilities of five children with
      Williams syndrome (four males aged 9 years 3 months, 7 years 11 months, 8 years 1
      month, and 10 years 8 months respectively, and one female aged 6 years 3 months).
      First, the children's visuospatial abilities were examined by asking them to copy
      a figure. Second, their cognitive processing abilities were assessed using the
      Japanese Kaufman Assessment Battery for Children. This test was used because it
      is an objective one, standardized in Japan, and is a measure of fluid ability
      including spatial localization. Participants scored significantly low on the
      spatial memory subtest indicating that there was a deficit in spatial
      localization. Children's performance in line copying tasks improved when the dots
      were in colour. Results suggest a deficit in the dorsal stream of visual
      cognition, with a relatively preserved ventral stream.

PMID- 11570633
TI  - Neuropsychological profile of a 9-year-old child with subcortical band
      heterotopia or 'double cortex'.
AB  - Subcortical band heterotopia (SBH) or 'double cortex', is a congenital brain
      abnormality that results from aberrant migration of neurons during development of
      the cortex. MRI shows a continuous band of heterotopic grey matter located
      between the cortex and ventricular walls, separated from them by a thin layer of
      white matter. The condition is quite rare, found predominantly in females, and is
      occasionally familial with an X-linked dominant inheritance. Current research has
      focused on genetic and neurological correlates, with cognitive assessment
      restricted to a global measure of general intellectual functioning. This paper
      describes in detail the results of a neuropsychological assessment of a 9-year
      old female recently diagnosed with SBH. Predominant features were a significantly
      reduced speed of processing for visuomotor and oral output and reduced immediate
      registration of information. This difficulty has functional implications
      affecting skill acquisition, learning in the classroom, and social interaction.

PMID- 11570632
TI  - Diagnosing children presenting with asymmetric pendular nystagmus.
AB  - Horizontal asymmetric nystagmus usually occurs in one of three situations:
      secondary to an intracranial lesion, with monocular visual loss, or as part of
      the triad that constitutes the diagnosis of spasmus nutans (asymmetric nystagmus,
      abnormal head posture, head shake). Clinical records of 277 children, presenting
      with congenital nystagmus over an 8-year period were reviewed. Nystagmus was
      asymmetric in 24 of 277 cases. Seven of these patients were diagnosed with
      spasmus nutans. This is a rare condition that is only diagnosed retrospectively
      based on the absence of any abnormal neuroimaging or electrophysiological
      findings. Twelve of 24 patients had intracranial pathology and all had abnormal
      visual evoked potentials (VEPs). Five patients were diagnosed with congenital
      sensory defect nystagmus including one with albinism, three with congenital cone
      dysfunction, and one with cone-rod dystrophy. This paper stresses that although
      neuroimaging is necessary in all patients presenting with asymmetric nystagmus,
      such nystagmus can also occur with retinal disease or albinism and indicates the
      importance of non-invasive VEP/ERG testing in all forms of nystagmus.

PMID- 11570634
TI  - Adult outcome of childhood learning disability.

PMID- 11570635
TI  - Advances in the treatment of lysosomal storage disease.

PMID- 11570636
TI  - 'What's in a name?'.

PMID- 11570637
TI  - 'Diffuse cerebrospinal gliomatosis'.

PMID- 11570638
TI  - Synergistic immunopotentiating effects induced by T-cell and B-cell superantigen
      in mice.
AB  - Staphylococcal Enterotoxin-A(SEA), a 27kDa monomeric protein, produced by some
      strains of Staphylococcus aureus, is a prototype T-cell superantigen which causes
      proliferation of cytotoxic T-lymphocytes and produces cytokines like TNF-alpha
      and IFN-gamma. Recently Protein A (PA), a 42 kDa membrane protein of the
      Staphylococcus aureus Cowan-I strain, has been termed a B-cell super antigen. It
      has been shown to cause multiple immunological responses. In the present study we
      examined the effect of these two superantigens used separately as well as
      combination in a normal mouse system. It has been shown that combination
      treatment of PA and SEA is more effective than that of each individual one. FACS
      analyses of cell cycles showed that a finely turned cellular collaboration
      occurred in various phases of cell growth and proliferative response compared
      with controls (P<0.01). It has also been shown that the percentage of various
      cell types bearing different clusters of differentiation markers, e.g., CD8+,
      CD34+ increases considerably due to the combined effect of PA and SEA. We also
      observed that co-administration of both the elicits different soluble mediators
      like cytokines (TNF-alpha, INF-gamma, IL-1beta). No apoptotic phenomenon was
      observed (from the cell cycle analysis) for the dose of PA and SEA, used for the
      experiments, suggesting that these doses of PA and SEA should be non-toxic.

PMID- 11570639
TI  - Natural killer cell activity, serum immunoglobulins, complement proteins, and
      zinc levels in patients with psoriasis vulgaris.
AB  - The role of the immune system in patients with psoriasis vulgaris (PV) was
      investigated. The genetic and immunological basis for psoriasis is still unknown.
      Because of the reports of immunological defects in this disease, we investigated
      serum levels of immunoglobulins IgG, IgM, IgA, complement proteins C3, C4, serum
      zinc (Zn) levels and natural killer (NK) cell activities. Skin lesions of the
      psoriatic patients involved in the study comprised less than 10 % of the total
      body and the disease was in a stationary period. Zn levels were measured by
      atomic absorption spectrophotometry. NK cell activity was measured by 51Cr (Na2
      51CrO4). IgG, IgA, IgM, C3 and C4 assays were done by liquid-phase
      immunoprecipitation assay with nephelometric endpoint detection. IgG, IgA, C3 and
      C4 levels were significanty higher in patients with PV than in healty controls (p
      < 0.05). However, NK cell activity, serum Zn and IgM levels did not show
      significant differences between these two groups. There are changed immunological
      responses, which may play an important role in the pathogenesis of the disease.
      Many controversial results have been related to immunological parameters in
      psoriatic patients. Therefore, more detailed studies in this field need to be
      done to determine the relationship between psoriasis and the immune system.

PMID- 11570640
TI  - A multi-laboratory evaluation of an enzyme-linked immunoassay quantitating human
      antibodies to Streptococcus pneumoniae polysaccharides.
AB  - An enzyme-linked immunoassay (EIA) is described and evaluated which quantitates
      human antibodies to serotype specific S. pneumoniae polysaccharide (PnPs) in
      human sera. Based on the observations previously described by Koskela (1), native
      PnPs are used as coating antigens and sera are absorbed with a soluble
      pneumococcal absorbant material containing C-polysaccharide (CPs) to ensure
      measurement of serotype specific anti-PnPs antibodies. The robustness of this
      method was evaluated by ten laboratories using the same reagents, protocol, and
      five human serum samples. Reproducible antibody values were obtained for IgM,
      IgG, and IgA antibodies to five different PnPs serotypes, 3, 6B, 14, 19F, and
      23F. The overall mean percent coefficients of variation in this interlaboratory
      study for all five selotype specific anti-PnPs determinations with the five coded
      sera were 30% for IgG, 3/% for IgM, and 36% for IgA. This assay can be
      standardized for quantitation of serotype specific anti-PnPs antibodies, allowing
      comparison of antibody values in vaccine trials evaluating pneumococcal vaccines.

PMID- 11570641
TI  - Effect of anti-IL-6 and anti-10 monoclonal antibodies on the suppression of the
      normal T lymphocyte mitogenic response by steady state sickle cell disease sera.
AB  - Previously published work has shown that sera from healthy sickle cell disease
      (SCD) patients inhibits normal lymphocyte mitogenic response to
      phytohemagglutinin (PHA) in vitro. The current study is to attempt to ascertain
      what effect antibody to type 2 cytokines, interleukin (IL)-6 and 10, have on the
      suppression of lymphocyte PHA response by SCD sera. Peripheral blood mononuclear
      cells (PBMC), separated by density gradient were obtained from 2 healthy normal
      donors. Sera from 50 healthy SCD patients, 50 normal healthy controls and pooled
      normal O, Rh+ (O+) sera were utilized in standard in vitro PHA stimulation of
      PBMC cultures. Mitogenic responses were expressed as mean counts per minute (cpm)
      of triplicate cultures. Fifty triplicate cultures of PHA stimulated normal PBMC
      were done with 10% normal pooled O+, normal control and SCD steady state sera
      only. In addition 50 cultures were done with SCD sera containing 1 microg/ml of
      anti-IL-6 monoclonal antibody, as well as 28 SCD serum cultures containing 1
      microg/ml of anti-IL-10 monoclonal antibody. The final 11 SCD serum culture
      experiments contained a combination of both anti-IL-6 and anti-IL-10 antibody,
      each at the concentration of 1 microg/ml. Results revealed > 15% suppression of
      mitogenic response in the SCD sera supplemented cultures as compared to control
      sera in 47/50 (94%) and in 40/50 (80%) of normal pooled O+, as calculated by mean
      cpm. The degree of suppression ranged from 17% to 98% in individual experiments.
      The addition of anti IL-6 antibody alone significantly improved mean cpm (> 20%)
      in 19/50 (38%) of SCD serum responses compared to O+ sera and 23/50 (46%) of
      control sera. Complete correction occurred in 9/50 (18%) of all SCD serum
      suppressions as compared to O+ sera and 6/50 (12%) when compared to control sera.
      Similarly, anti-IL-10 antibody decreased suppression of the mean cpm of SCD serum
      cultures in 18/28 (64%) and completely corrected 3/18 (11%). The combined
      antibody data revealed >20% increase in mean cpm in 10/11(91%) experiments.
      Inhibitors of mitogenic response were present in a significant percentage of the
      SCD sera utilized in the present study. The significant corrective effects of
      both monoclonal antibodies would seem to support the original hypothesis that
      high circulating levels of type 2 cytokines may represent the cell-mediated
      dependent inhibitory factors expressed in the sera of many healthy SCD patients.

PMID- 11570642
TI  - Role of IL-18 in the secretion of Il-1beta, sIL-1RII, and IL-1Ra by human
      neutrophils.
AB  - In the present study we investigated the effect of IL- 18 on the production of IL
      1beta, IL-1Ra and sIL-1RII by human neutrophils. Our observations indicate that
      rhIL-18 induces IL-1beta and, to a lesser extend, IL-1Ra and sIL-1RII production
      by human neutrophils isolated form peripheral blood. However, this effect was
      less important in comparison with LPS-stimulation. Moreover, the results obtained
      suggest that IL-18 can induce priming of neutrophils for IL-1beta and, to a
      lesser extend, IL- Ra and sIL-1RII production by LPS-stimulated cells. The
      capacity of IL-18 to serve as an effective modulator for IL-1beta and its
      regulatory proteins may have significance in the inflammatory and immune
      reactions mediated by IL-1beta.

PMID- 11570643
TI  - Effects of dexamethasone on the expression of Fas molecules and apoptosis of
      lymphocytes in patients with systemic lupus erythematosus.
AB  - Previous studies have shown that the autoimmune phenomenon could be caused by
      defective apoptosis of autoreactive lymphocytes. Corticosteroids used for
      treatment of systemic lupus erythematosus (SLE) are potent apoptosis inducers. We
      examined dexamethasone (DEX)-induced apoptosis and Fas expression in peripheral
      blood lymphocytes of SLE patients and normal subjects. Peripheral blood
      lymphocytes were obtained from 40 SLE patients and 18 sex- and age-matched
      control subjects. Percentages of apoptosis and expression of Fas molecule in
      lymphocytes were assessed by flow cytometry. Fas expression in lymphocytes
      treated with or without DEX was significantly higher in SLE patients than normal
      controls [median (interquartile range) of mean fluorescence intensity without
      DEX: 74.9 (50.7-98.0) vs 20.0 (17.7-25.0), p < 0.001; with DEX: 77.9 (56.0-130.5)
      vs 20.5 (18.6-24.7), p<0.001]. DEX (0.1-5 microM) could also induce apoptosis of
      lymphocytes from SLE and control subjects in a dose-dependent manner. Elevation
      of apoptotic susceptibility was more prominent in DEX-treated SLE lymphocytes
      [33.9% (24.7-37.5%) vs 19.6% (13.6-26.1 %), p = 0.003]. The higher apoptotic
      susceptibility of SLE lymphocytes upon DEX treatment in vitro may be related, at
      least partly, to the pharmacological action of corticosteroids.

PMID- 11570644
TI  - Modulation of the severity of experimental autoimmune encephalomyelitis by
      gammadelta T lymphocytes activated by mycobacterial antigens.
AB  - Immunity to mycobacterial antigens may contribute to the maintenance of self
      tolerance. Exposure of the immune system to mycobacterial antigen might well
      stimulate the immune system to exert control over unwanted self-reactive clones.
      We demonstrated that in vivo administration of Mycobacterium tuberculosis, PPD,
      and PPD peptide (180-196) prior to immunization with Myelin Basic Protein (MBP)
      led to a moderate increase of gammadelta T cells, suppression of the immune
      response, and reduction in the severity of Experimental Autoimmune
      Encephalomyelitis. The immunosuppression observed is due, at least in part, to
      the production of Transforming growth factor-beta (TGFbeta) by the gammadelta T
      lymphocytes.

PMID- 11570645
TI  - Discrimination and unfair treatment: relationship to cardiovascular reactivity
      among African American and European American women.
AB  - This study examined the relationship of cardiovascular reactivity to both
      interpersonal mistreatment and discrimination in a community-based sample of
      African American and European American women (N=363) in midlife. Subtle
      mistreatment related positively to diastolic blood pressure (DBP) reactivity for
      African American participants but not their European American counterparts.
      Moreover, among the African American participants, those who attributed
      mistreatment to racial discrimination exhibited greater average DBP reactivity.
      In particular, these women demonstrated greater DBP reactivity to the speech
      task, which bore similarities to an encounter with racial prejudice but not to a
      nonsocial mirror tracing task. These findings are consistent with the hypothesis
      that racial discrimination is a chronic stressor that can negatively impact the
      cardiovascular health of African Americans through pathogenic processes
      associated with physiologic reactivity.

PMID- 11570646
TI  - Expectancy-value constructs and expectancy violation as predictors of exercise
      adherence in previously sedentary women.
AB  - This prospective study examined effects of expectancy of exercise benefits, value
      of benefits, expectancy violation, and self-efficacy (SE) on exercise behavior
      and study dropout in sedentary women (n=86). SE predicted exercise for study
      completers but did not predict study dropout. After 6 and 12 weeks, participants
      evidenced expectancy violations, particularly for fitness and weight. Initial
      value, expectancy, and Expectancy X Value did not predict exercise for study
      completers, but dropouts had higher initial positive expectancies than did
      completers. Expectancy violations produced in Weeks 1-6 did not predict exercise
      in Weeks 7-12 in study completers, but dropouts in Weeks 7-12 had higher
      expectancy violations for weight in Weeks 1-6 than did completers. Follow-up
      revealed that study dropouts stopped exercising. Identifying individuals with
      high initial expectancies and expectancy violations may improve health behavior
      intervention and research.

PMID- 11570647
TI  - Reasons for quitting smoking among low-income African American smokers.
AB  - The psychometric characteristics of the Reasons For Quitting scale (RFQ) were
      assessed among a sample of African American smokers with low income (N=487). The
      intrinsic and extrinsic scales and their respective subscales were replicated. As
      hypothesized, higher levels of motivation were associated significantly, in
      patterns that supported the measure's construct validity, with advanced stage of
      readiness to quit smoking, greater perceived vulnerability to health effects of
      smoking, and greater social support for cessation. On the basis of the present
      study, the RFQ might best predict short-term cessation among older and female
      smokers. Refinement of the RFQ is needed to assess intrinsic motivators other
      than health concerns and to identify salient motivators for young and male
      smokers.

PMID- 11570648
TI  - The nature of the association between diet and serum lipids in the community: a
      twin study.
AB  - Diet is commonly thought to be an environmental influence on serum lipid
      concentrations. This study evaluated whether total caloric and fat intake predict
      total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density
      lipoprotein cholesterol (HDL), and triglyceride (TRIG) concentrations for
      environmental, as compared with genetic, reasons among 137 monozygotic and 67
      dizygotic young adult twins. When genetic influences were controlled by
      correlating differences between monozygotic co-twins, a significant association
      remained between diet and TC, LDL, and HDL, suggesting that these dietary and
      serum lipid measures correlate for environmental reasons. Twin structural
      equation modeling confirmed these results. Overall, these results provide
      additional support for the hypothesis that diet is an environmental influence on
      TC, LDL, and HDL.

PMID- 11570649
TI  - Changes in health-promoting behavior following diagnosis with HIV: prevalence and
      correlates in a national probability sample.
AB  - Diet, exercise, smoking, and substance use patterns affect the course of illness
      and quality of life for people with HIV. In interviews with a national
      probability sample of 2,864 persons receiving HIV care, it was found that most
      had made health-promoting changes in one or more of these behaviors since
      diagnosis. Many reported increased physical activity (43%) and improved diet
      (59%). Forty-nine percent of cigarette smokers quit or cut down; 80% of substance
      users did so. Desire for involvement in one's HIV care and information seeking
      positive coping were the most consistent correlates of change. Other correlates
      varied by health practice but included health status, emotional well-being,
      demographics, and attitudes toward other aspects of HIV care. Most people with
      HIV improve their health behavior following diagnosis, but more might be helped
      to do so by targeting these behaviors in future interventions.

PMID- 11570650
TI  - Cigarette smoking and chewing gum: response to a laboratory-induced stressor.
AB  - The current study examined the anxiolytic effects of cigarette smoking and
      chewing gum on urge to smoke, withdrawal, and anxiety in response to a public
      speaking task in 45 undergraduate smokers. Participants were asked to smoke, chew
      gum, or do nothing in response to the stressor. Participants completed measures
      of anxiety, withdrawal symptoms, and urge to smoke pre- and poststressor. The
      smoke group reported fewer urges to smoke pre- and poststressor than the other
      groups. The smoke and gum groups reported fewer withdrawal symptoms than did the
      control group poststressor. Chewing gum was helpful in managing levels of
      withdrawal symptoms compared with the control group. Groups did not differ on
      measures of anxiety. Results suggest that smoking in response to a stressor may
      not reduce levels of affective stress. Furthermore, chewing gum may be helpful in
      managing withdrawal symptoms in response to a stressor.

PMID- 11570651
TI  - Social-cognitive theory mediators of behavior change in the National Institute of
      Mental Health Multisite HIV Prevention Trial.
AB  - The National Institute of Mental Health Multisite HIV Prevention Trial was a
      trial of an intervention to reduce sexual HIV risk behaviors among 3,706 low
      income at-risk men and women at 7 U.S. research sites. The intervention, based on
      social-cognitive theory and designed to influence behavior change by improving
      expected outcomes of condom use and increasing knowledge, skills, and self
      efficacy to execute safer sex behaviors, was effective relative to a control
      condition in reducing sexual risk behavior. At 3 months after completion of the
      intervention, measures of these potential mediators were higher in the
      intervention than in the control condition. Although the effect of the
      intervention on sexual risk behavior was significantly reduced when the variables
      were controlled statistically, supporting the hypothesis of their mediation of
      the intervention effect, most of the effect remained unexplained, indicating the
      influence of unmeasured factors on outcome.

PMID- 11570652
TI  - From adolescence to adulthood: age-related changes in beliefs about cigarette
      smoking in a midwestern community sample.
AB  - The current study used a cohort-sequential design to examine age-related changes
      in health-relevant beliefs from the middle school years through age 37 in a
      large, midwestern, community sample (N=8,556). Results suggest systematic age
      related changes such that beliefs in the personalized risks of smoking declined
      in middle school and then increased, beliefs in generalized health risks
      increased beginning in the middle school years, and values placed on health as an
      outcome decreased in the high school years and then increased. These findings
      suggest that intervention programs must counter declining personalized risk
      perceptions among middle school students and declining values placed on health
      among high school age students.

PMID- 11570653
TI  - Long-term effects of educational and peer discussion group interventions on
      adjustment to breast cancer.
AB  - The authors report a 3-year follow-up of the effects of 8-week support group
      interventions on the quality of life of women with early stage breast cancer.
      Shortly after diagnosis, women were randomly assigned to 1 of 4 conditions:
      control, education, peer discussion, and education plus peer discussion. The
      education group intervention focused on providing information to enhance control
      over the illness experience, whereas the peer discussion group intervention
      focused on providing emotional support through the expression of feelings.
      Consistent with the results that emerged 6 months after the interventions (V. S.
      Helgeson, S. Cohen, R. Schulz, & J. Yasko, 1999), the authors found that the
      benefits of the education intervention were maintained over a 3-year period
      (N=252), although effects dissipated with time. The authors continued to find no
      benefits of the peer discussion intervention, either alone or in combination with
      education.

PMID- 11570654
TI  - The paradox of statistical power and publication bias.

PMID- 11570655
TI  - Are power analyses of published literature valuable?

PMID- 11570656
TI  - Smoking diminishes the beneficial effect of statins: observations from the
      landmark trials.
AB  - The landmark statin trials showed a significant reduction in morbidity and
      mortality associated with ischemic heart disease. However, it may not be widely
      appreciated that smoking had a marked adverse effect on outcome in these trials.
      In both the primary and secondary prevention setting, the effect of smoking was
      broadly similar. Smoking markedly increased the risk of events in the placebo and
      treatment groups. For example, in the primary prevention trials, this risk was 74
      86% higher when smokers were compared with nonsmokers in the placebo groups. The
      corresponding figures for the secondary prevention trials were 23-61%. The risk
      of events in untreated nonsmokers was of a similar order to that seen in smokers
      taking statins. Although statin treatment was associated with a significant
      reduction in events in smokers, the best outcome was observed in nonsmokers
      treated with statins (primary prevention: lovastatin or pravastatin; secondary
      prevention: pravastatin or simvastatin). The highest risk of events in any group
      was in the smokers on placebo. This information may increase clinician and
      patient awareness as to the marked harmful effect of smoking relative to
      effective, evidence-based treatment (ie, the use of statins).

PMID- 11570657
TI  - Extent of coronary atherosclerosis and homocysteine affect endothelial markers.
AB  - The aim of the study was to evaluate the effects of the presence, extent, and
      clinical stability of coronary artery disease on endothelial function parameters,
      C-reactive protein and homocysteine levels. Fifty-eight patients with
      angiographically documented coronary artery disease and 25 patients with normal
      coronary arteries were evaluated for risk factors, plasma homocysteine, C
      reactive protein, and soluble adhesion molecule levels. Vascular cell adhesion
      molecule-1 and sE-selectin were significantly higher in the group with coronary
      artery disease than in healthy subjects (p = 0.005 and p = 0.031, respectively).
      Patients with unstable angina had significantly higher C-reactive protein (p <
      0.001), troponin I (p < 0.01), and leukocyte counts (p < 0.05) than those with
      stable angina. sE-selectin levels were correlated with the extent of coronary
      atherosclerosis (r = 0.444, p < 0.05), and plasma homocysteine levels were
      associated with vascular cell adhesion molecule-1 (r = 0.479, p < 0.05) in
      unstable cases. These results suggest that vascular cell adhesion molecule-1 and
      sE-selectin are useful for determining the presence of coronary atherosclerosis,
      whereas C-reactive protein, troponin 1, and leukocyte count are predictors of
      clinical stability.

PMID- 11570658
TI  - The effects of right ventricular involvement on heart rate variability and
      ventricular late potentials in acute inferior myocardial infarction.
AB  - Depressed heart rate variability and presence of ventricular late potentials in
      acute myocardial infarction are associated with a poor prognosis. Although it is
      known that the abnormalities vary according to anterior or inferior location of
      acute myocardial infarction, the relationship with right ventricular acute
      myocardial infarction is not clear. The effects of right ventricular myocardial
      infarction on heart rate variability and ventricular late potentials are studied.
      The study was performed with a total of 46 patients (38 males; aged 56 +/-13 yr,
      range, 33 to 70 yr). Twenty-six patients had isolated inferior myocardial
      infarction while 20 patients had accompanying right ventricular involvement. For
      all patients, ambulatory Holter recordings between 24 and 48 hours following
      myocardial infarction, echocardiography in first 48 hours, and signal-averaged
      electrocardiography with submaximal exercise at average day 6 (range, 5 to 8
      days) were performed. Heart rate variability and signal-averaged
      electrocardiography recordings were repeated after discharge (average, 39 days).
      During the first 24 to 48 hr, time domain parameters (SDNN1 and SD1) were
      significantly lower (SDNN1: 62 +/- 17 vs 100 +/- 20 ms, p = 0.001; SD: 37 +/- 10
      vs 50 +/- 16 ms, p = 0.03) in patients with isolated inferior MI than in those
      with right ventricular involvement, whereas root-mean-square voltage (RMS-SD1)
      showed no significant difference in both groups (28 +/- 7 vs 35 +/- 8 ms). In
      post-discharge heart rate variability recordings, there were no significant
      differences (SDNN2: 86 +/- 13 vs 95 +/- 15 ms; SD2: 48 +/- 11 vs 57 +/- 13 ms;
      RMS-SD2: 32 +/- 14 vs 35 +/- 9 ms). In pre-discharge tests, the mean value of low
      amplitude signals (LAS1) was higher (26 +/- 9 vs 33 +/- 11 ms, p = 0.03) in
      patients with isolated inferior myocardial infarction than in those with right
      ventricular involvement, while other signal-averaged electrocardiography
      parameters were not significantly different (filtered QRS: 102 +/- 5 vs 105 +/-
      10 ms, RMS-40(1): 44 +/- 13 vs 26 +/- 10 microV; incidence of ventricular late
      potentials: 23% vs 30%, p = NS, respectively). In post-discharge tests, all of
      signal-averaged electrocardiography parameters were similar in both groups
      (filtered QRS2: 112 +/- 12 vs 114 +/- 8 ms, LAS2: 28 +/- 9 vs 32 +/- 13 ms, RMS
      40(2): 36 +/- 10 vs 34 +/- 11 microV, and frequency of ventricular late
      potentials2: 23% vs 30%, p = NS). These data suggest that right ventricular
      involvement in an acute inferior myocardial infarction is associated with
      improved heart rate variability parameters but not ventricular late potentials in
      pre-discharge period. However, the influence of right ventricular involvement on
      heart rate variability parameters fades away in the post-discharge period.

PMID- 11570659
TI  - Association between erythrocyte mean corpuscular volume and peripheral arterial
      disease in male subjects: a case control study.
AB  - Elevated serum total homocysteine, an established risk factor for peripheral
      arterial disease, is influenced by the vitamin B12 and folate status. Since these
      vitamins are inversely correlated with erythrocyte mean corpuscular volume, an
      investigation of whether mean corpuscular volume is higher in patients with
      symptomatic peripheral arterial disease than in healthy subjects was performed.
      Furthermore, a determination of predictors of increased mean corpuscular volume
      levels in this population free of symptomatic coronary artery disease,
      cerebrovascular disease, and diabetes mellitus was carried out. From 469
      consecutive patients with symptomatic peripheral arterial disease, 100 fulfilled
      study inclusion criteria. Peripheral arterial disease was confirmed by
      angiography. One hundred age-matched subjects without peripheral arterial disease
      as verified by ankle-brachial index measurements >0.9 served as control subjects.
      Patients with PAD displayed a significantly higher mean corpuscular volume level
      (94.5 fl) than control subjects (90.9 fl, p<0.001). Logistic regression analysis
      showed that current smoking status (p<0.001) and mean corpuscular volume
      (p=0.009), but not total homocysteine or lipid parameters discriminated case
      control status. In addition, logistic regression analysis revealed a relationship
      of mean corpuscular volume with smoking (p=0.001), gamma-glutamyltransferase
      (p<0.001), and total homocysteine (p=0.012). This model predicted mean
      corpuscular volume values with an accuracy of 83%. Elevated mean corpuscular
      volume is a predictor of symptomatic peripheral arterial disease in the sample
      studied. A deficiency of folate and/or vitamin B12 may be responsible for this
      observation, as indicated by the correlation of mean corpuscular volume with
      total homocysteine. Due to the additional association of mean corpuscular volume
      with smoking and gamma-glutamyltransferase, an unhealthy lifestyle with low
      vitamin intake may cause elevated mean corpuscular volume values in patients with
      PAD.

PMID- 11570660
TI  - The significance of Chlamydia pneumoniae in symptomatic carotid stenosis.
AB  - An association between symptomatic carotid stenosis and recent infection with
      Chlamydia pneumoniae is reported. Thirty-five patients (20 symptomatic and 15
      asymptomatic) with carotid stenosis of 70% to 90% underwent carotid
      endarterectomy. Endarterectomy was performed without patch and shunt; the average
      occlusion time of the internal carotid artery was 14 +/- 3 min. The atheromatic
      plaque and a portion of the thyroid artery were examined with polymerase chain
      reaction and peripheral vein blood was obtained for serologic detection of
      systematic infection, and IgG and IgM antibodies to C. pneumoniae by enzyme
      linked immunosorbent assay. Twenty of 35 patients (57.1%) had increased titers of
      IgG antibodies to C. pneumoniae. Eight patients revealed IgG plus IgM antibodies;
      two of the eight had IgG, IgM, and positive findings on polymerase chain
      reaction. No C. pneumoniae was detected on the thyroid arteries. Sixty-five
      percent (13/20) of the patients with increased IgG antibodies to C. pneumoniae,
      87.5% (7/8) with IgG + IgM, and 100% with IgG + IgM + positive polymerase chain
      reaction were symptomatic. Plaque morphology in association with symptoms did not
      reveal a significant correlation between soft plaques and symptoms, whereas the
      majority of the symptomatic patients had plaques of type III-V. Patients having
      recent contamination and positive polymerase chain reaction had a significant
      relationship between C. pneumoniae infection and symptomatic carotid disease.
      This supports the hypothesis that C. pneumoniae infection can produce a kind of
      instability of the carotid plaque. The results of this study demonstrate that
      patients with advanced atherosclerotic carotid disease have an increased
      incidence of C. pneumoniae infection. Recent infection could be responsible for
      instability of the carotid plaque, causing cerebral ischemic episodes.

PMID- 11570661
TI  - Effect of blood pressure reduction on abnormal left atrial appendage function in
      untreated systemic hypertensive patients with sinus rhythm.
AB  - To investigate whether reduction in blood pressure has a beneficial effect on
      left atrial appendage (LAA) function, the authors evaluated 24 untreated systemic
      hypertensive patients with normal left ventricular systolic function in sinus
      rhythm at baseline and at 3 months after initiation of antihypertensive therapy.
      They performed transthoracic and transesophageal echocardiographic examinations
      in hypertensive patients before and after treatment of hypertension. Three of the
      24 patients had blood pressure that failed to respond to the regimen of
      antihypertensive therapy and were removed from the analysis. Of the remaining 21
      patients, mean systolic and diastolic blood pressures at baseline were 170 +/- 18
      and 104 +/- 6 mm Hg, respectively, and fell significantly at 3 months to 141 +/-
      10 and 90 +/- 5 mm Hg, respectively, (p<0.001) after initiation of
      antihypertensive therapy. There was no significant change in heart rate with
      treatment (baseline 81 +/- 8 and at 3 months 84 +/- 9 beats/min). There was no
      significant change in left ventricular end-diastolic diameter, left ventricular
      ejection fraction, left ventricular wall thickness, or left atrial diameter from
      baseline (49 +/- 4 mm, 58 +/- 5%, 12 +/- 1 mm, and 41 +/- 4 mm, respectively) at
      3 months (48 +/- 5 mm, 59 +/- 4%, 12 +/- 1 mm, and 40 +/- 3 mm). The treatment
      caused a significant reduction in maximal LAA areas (6.3 +/- 1.3 cm2 at baseline,
      4.6 +/- 0.7 cm2 at 3 months, p<0.001), with a concomitant increase in LAA
      emptying velocity (44 +/- 7 cm/sec at baseline, 60 +/- 9 cm/sec at 3 months,
      p<0.001). In conclusion, these findings suggest that reduction in blood pressure
      with antihypertensive therapy could improve LAA function in hypertensive patients
      with normal left ventricular systolic function in sinus rhythm.

PMID- 11570662
TI  - Adenoviral-mediated transfer of tissue plasminogen activator gene into brain
      capillary endothelial cells in vitro.
AB  - Tissue plasminogen activator (tPA) has a critical role in fibrinolysis,
      converting plasminogen into active protease plasmin. Because intravenous tPA has
      only limited effectiveness as acute stroke therapy, enhancement of endogenous tPA
      represents a potential alternative to stroke treatment. Adenoviral-mediated gene
      transfer was used to enhance production of tPA in bovine brain capillary
      endothelial cells (BEC). Antigen and activity levels of tPA and plasminogen
      activator inhibitor-1 (PAI-1) in media from BEC infected with AdCMVtPA were
      analyzed. Conditioned media were analyzed for thrombomodulin, the integral
      membrane antithrombotic molecule that co-activates protein C. BEC infected with
      AdCMVtPA demonstrated enhanced expression of tPA antigen (40.2 +/- 0.4 ng/mL vs
      1.1 +/- 1.5 ng/mL [p<0.001] and 0.3 +/- 0.5 ng/mL [p<0.0001], respectively) and
      increased tPA enzymatic activity (27.4 +/- 5.7 IU/mL vs 8.3 +/- 1.7 IU/mL
      [p<0.05] and 13.3 +/- 3.2 IU/mL [p<0.05], respectively) compared to BEC infected
      with the control adenovirus (Adl327) or uninfected BEC. There was a moderate
      increase in PAI-1 protein 4 days after transfection with AdCMVtPA, and the
      integral membrane protein thrombomodulin was released into media by transfected
      BEC. These results demonstrate that adenoviral-mediated delivery in vitro of the
      human tPA gene resulted in high levels of expression of tPA in BEC. Transient
      overexpression of tPA by gene transfer might be a useful strategy to protect
      against thrombotic occlusion during the period of risk of acute stroke.

PMID- 11570663
TI  - Recombinant tissue plasminogen activator for the treatment of cutaneous
      infarctions in antiphospholipid antibody syndrome: a case report.
AB  - Antiphospholipid antibody syndrome (APAS) commonly presents with cutaneous
      infarctions mimicking thromboembolic vaso-occlusive disease. Systemic
      anticoagulation is the standard of care for this disorder, but treatment failures
      can occur. The authors report the first successful treatment of cutaneous
      infarctions due to APAS with low-dose, intravenous tissue plasminogen activator
      (rTPA) in a patient who failed to improve with high-dose anticoagulation. Wound
      healing was associated with a marked improvement in blood flow as assessed by
      scanning laser Doppler. The authors recommend that patients presenting with
      cutaneous infarctions in the absence of atherosclerosis be evaluated for APAS,
      and that fibrinolytic therapy be considered if cutaneous infarction persists
      despite anticoagulant therapy.

PMID- 11570664
TI  - Squamous cell carcinoma of the lung presenting with cutaneous leukocytoclastic
      vasculitis: a case report.
AB  - An elderly patient with paraneoplastic cutaneous leukocytoclastic vasculitis
      (CLV) leading to the discovery of an as-yet asymptomatic, potentially surgically
      curable squamous cell carcinoma of the lung is presented. This type of vasculitis
      has not been previously described in association with this type of lung cancer.
      Since vasculitic paraneoplastic syndromes, including CLV, may develop before the
      clinical presentation of malignant tumors, the present case and others previously
      reported strongly suggest that in apparently idiopathic CLV, patients should be
      evaluated for the presence of occult malignancy that could be curable by early
      detection.

PMID- 11570665
TI  - Angiotensin-converting-enzyme inhibitor administration must be monitored for
      serum amylase and lipase in order to prevent an acute pancreatitis: a case
      report.
AB  - Some clinical cases published in literature show that angiotensin-converting
      enzyme (ACE)-inhibitor administration may cause acute pancreatitis. In this work,
      the authors report a case of a patient affected by hypertension. Upon admission,
      the authors started antihypertensive therapy using captopril, which caused an
      important amylase and lipase rise within 13 days. When the ACE-inhibitor therapy
      was stopped, a rapid decrease of the serum enzyme was observed within 3 days. The
      high levels of serum amylase and lipase were linked to neutrophilia but were not
      associated with relevant symptomatic findings or features of pancreatopathy. The
      absence of the usual conditions that may cause pancreatitis, such as biliary
      stasis, hypercalcemia, or alcohol abuse, and the rapid decrease of serum enzyme
      levels after drug suspension suggested an ACE-inhibitor-induced pancreatitis.
      This is the first clinical report of an ACE-inhibitor-induced pancreatitis in
      which captopril administration was found after hospitalization. The drug
      suspension probably prevented other complications. This case report suggests
      that, when ACE-inhibitor administration is started, serum amylase and lipase
      should be monitored in order to prevent acute pancreatitis without waiting for
      clinical evidence of a pancreatopathy.

PMID- 11570666
TI  - Anomalous coronary artery origin associated with bicuspid aortic valve in a
      patient with rheumatic mitral stenosis: a case report.
AB  - A rare case of an anomalous left coronary artery arising from the right sinus of
      Valsalva associated with bicuspid aortic valve is presented. This case is unique
      because these congenital anomalies were associated with rheumatic mitral
      stenosis. This anomalous coronary origin was found at catheterization before
      balloon mitral valvuloplasty. The clinical significance of this finding is
      discussed.

PMID- 11570667
TI  - Time course of pulmonary response of rats to inhalation of crystalline silica:
      histological results and biochemical indices of damage, lipidosis, and fibrosis.
AB  - Previous studies have determined that alpha-quartz (crystalline silica) can cause
      pulmonary inflammation, damage, and fibrosis. However, the temporal relationship
      between silica inhalation and pulmonary inflammation, damage, and fibrosis has
      not been fully examined. To address this gap in our knowledge of silica-induced
      pulmonary fibrosis, a chronic inhalation study using rats was designed.
      Specifically, rats were exposed to a silica aerosol (15 mg/m3 silica, 6 h/d, 5
      d/wk, 116 d), and measurements of pulmonary inflammation, damage, and fibrosis
      were monitored throughout the study. We report (1) data demonstrating that the
      silica aerosol generation and exposure system produced a consistent silica
      aerosol of respirable size particles; (2) the time course of silica deposition in
      the lung; (3) calculations that demonstrate that the rats were not in pulmonary
      overload; (4) histopathological data demonstrating time-dependent enhancement of
      silica-induced alveolitis, epithelial hypertrophy and hyperplasia, alveolar
      lipoproteinosis, and pulmonary fibrosis in the absence of overload; and (5)
      biochemical data documenting the development of lipidosis, lung damage, and
      fibrosis.

PMID- 11570668
TI  - The quartz hazard: effects of surface and matrix on inflammogenic activity.
AB  - Modification of the quartz surface during the history of the particle is a
      powerful idea in understanding the variability of the quartz hazard. Interactions
      between quartz and other minerals are likely to occur in sediments, during
      industrial processing, or in matrix-bound quartz. We discuss new evidence
      regarding the basis of changes in the quartz surface that relate to changes in
      its ability to cause inflammation. Different samples of quartz were subjected to
      various biological assays. Endpoints included instillation of quartz into the
      tracheobronchial tree and measurement of PMN numbers in bronchoalveolar lavage
      (BAL) and in lung tissue, levels of the chemokine MIP-2 in BAL, and nuclear
      translocation of the transcription factor NF-kappaB in BAL cells. In vitro
      biological assays included cytotoxicity to epithelial cells, hemolytic activity,
      and radical activity of the particle surface as measured by electron spin
      resonance. Treatment of quartz with aluminium lactate impaired its ability to
      cause PMN recruitment, chemokine release, and NF-kappaB nuclear translocation in
      BAL. Workplace quartzes had no proinflammatory activity, which correlated with
      their ability to cause hemolysis but not their electron spin resonance (ESR)
      activity. Quartz in a matrix with coalmine dust or fly-ash showed different
      effects. In fly-ash, the toxicity was masked, but coalmine dusts were more toxic
      to epithelial cells than pure quartz in vitro; however, after instillation, the
      long-term inflammation was not related to the in vitro activity. Amelioration of
      quartz surface activity can occur in workplace samples of quartz and quartz
      samples whose surface is protected, to the extent that they have very little
      inflammogenic activity and display an inability to activate key subcellular
      pathways that lead to inflammation. Quartz from a workplace whose surface has
      been affected, or in a matrix such as coalmine dust or fly-ash, can have its
      toxicity modulated. These effects are due to minerals and organic compounds that
      can both decrease (e.g., aluminium salts) or enhance (e.g., coalmine dust matrix)
      biological activity and thus may contribute to toxicity in a complex way that is
      not easily predicted. Iron is a good example. There are reports that it can
      enhance quartz toxicity, or it may have little role to play in its toxicity, as
      shown here for almost pure quartz particles. A broad program of further research
      is needed before we have a sound understanding of the mechanisms of quartz
      toxicity.

PMID- 11570669
TI  - Reactivity of free radicals on hydroxylated quartz surface and its implications
      for pathogenicity experimental and quantum mechanical study.
AB  - We studied the adsorption of hydroxyl radicals and superoxide anion radicals on a
      hydroxylated alpha-quartz surface using cluster and periodic slab models by means
      of density functional calculations. Models of two hydroxylated alpha-quartz
      surfaces--(0001) and (0111)--have been used in the simulations. The hydroxyl
      radical adsorbs readily on both surfaces. The subsurface Si-O bonds are weakened
      during the adsorption resulting in surface layer destabilization. This
      destabilization leads directly to surface disintegration in the case of
      *OH/(0111) adsorption. The product of the surface disintegration and
      reconstruction is a surface terminated by silanol groups (Si-OH) and siloxyl
      radicals (Si-O*). The model calculations suggest that adsorption of *OH on a
      hydroxylated quartz surface transforms a chemically inert, aged, silanol
      terminated surface to a very reactive, silicon-based radical terminated surface.
      The activated surface may then cause oxidative damage to the adsorbed
      biomaterial. The superoxide anion radical adsorbs on both surfaces, but the
      adsorption products are only weakly bonded to the surface. The calculated energy
      barrier for the O2*- activated subsurface Si-O bond dissociation is 10 kcal/mol,
      which is higher than for the *OH activated process (4 kcal/mol). The calculated
      weaker bonding to the surface and higher activation energy barrier suggest that
      the superoxide anion radical will be less efficient in reactivation of an aged,
      hydroxylated quartz surface than the hydroxyl radical. The importance of the
      specific geometry of the surface silicon atoms on the surface reactivity and
      adsorption properties is also discussed. The theoretical predictions are
      supported experimentally using chemiluminescence to monitor reactivation of the
      aged silica surface by superoxide anion radicals.

PMID- 11570670
TI  - Inhaled amorphous silica particulates: what do we know about their toxicological
      profiles?
AB  - The International Agency for Research on Cancer (IARC) recently published a
      monograph on the evaluation of carcinogenic risks to humans of exposure to
      crystalline and amorphous silica particles. The IARC Working Group concluded that
      crystalline silica, in the form of quartz or cristobalite, from occupational
      sources posed a carcinogenic risk to humans (Category 1). IARC also determined
      that amorphous silica particles were not classifiable as to its carcinogenicity
      to humans (Category 3). With regard to amorphous silica, the evaluation was based
      primarily on the lack of toxicological and epidemiological data for these
      materials and this was noted in the IARC document. This manuscript is designed to
      provide a brief summary of the limited inhalation toxicity database related to
      amorphous silica particulates and to cite a few studies wherein the pulmonary
      toxicological effects of inhaled crystalline and amorphous silica particles were
      compared.

PMID- 11570671
TI  - Biological and statistical approaches to predicting human lung cancer risk from
      silica.
AB  - Chronic inflammation is a key step in the pathogenesis of particle-elicited
      fibrosis and lung cancer in rats, and possibly in humans. In this study, we
      compute the excess risk estimates for lung cancer in humans with occupational
      exposure to crystalline silica, using both rat and human data, and using both a
      threshold approach and linear models. From a toxicokinetic/dynamic model fit to
      lung burden and pulmonary response data from a subchronic inhalation study in
      rats, we estimated the minimum critical quartz lung burden (Mcrit) associated
      with reduced pulmonary clearance and increased neutrophilic inflammation. A
      chronic study in rats was also used to predict the human excess risk of lung
      cancer at various quartz burdens, including mean Mcrit (0.39 mg/g lung). We used
      a human kinetic lung model to link the equivalent lung burdens to external
      exposures in humans. We then computed the excess risk of lung cancer at these
      external exposures, using data of workers exposed to respirable crystalline
      silica and using Poisson regression and lifetable analyses. Finally, we compared
      the lung cancer excess risks estimated from male rat and human data. We found
      that the rat-based linear model estimates were approximately three times higher
      than those based on human data (e.g., 2.8% in rats vs. 0.9-1% in humans, at mean
      Mcrit lung burden or associated mean working lifetime exposure of 0.036 mg/m3).
      Accounting for variability and uncertainty resulted in 100-1000 times lower
      estimates of human critical lung burden and airborne exposure. This study
      illustrates that assumptions about the relevant biological mechanism, animal
      model, and statistical approach can all influence the magnitude of lung cancer
      risk estimates in humans exposed to crystalline silica.

PMID- 11570672
TI  - The role of inflammation, oxidative stress, and proliferation in silica-induced
      lung disease: a species comparison.
AB  - To gain a better understanding of the complex mechanisms at work in silica
      induced lung disease, we conducted studies comparing the rat and hamster response
      to silica (alpha-quartz). It has been hypothesized that the rat lung response to
      low-solubility particles, such as silica, may be due to the recruitment,
      activation, and subsequent release of damaging mediators by the inflammatory
      cells. Studies have suggested that hamsters and mice may be less sensitive to the
      inflammatory and tumorigenic effects of these low-solubility particles than rats.
      Differences in defense mechanisms, such as antioxidant levels or repair
      mechanisms, may play a key role in how different species respond to these
      particles. To investigate species differences in silica-induced lung response,
      this study compared the effects of alpha-quartz on rats and hamsters. Briefly,
      rats and hamsters were intratracheally instilled with saline or 0.2, 2, or 20 mg
      of alpha-quartz. Seven days after exposure, bronchoalveolar lavage (BAL) was
      performed, and the BAL fluid was evaluated for cell number, type, and LDH. In
      addition, lung tissue was evaluated for the expression of various pro- and anti
      inflammatory mediators. Both species showed dose-related increases in neutrophils
      and LDH after alpha-quartz exposure; however, the changes were significantly
      greater in the rat, and rats showed greater expression of several pro
      inflammatory mediators and lower levels of the anti-inflammatory mediators. These
      differences in pro- and anti-inflammatory mediators may contribute to the
      apparent species differences in tumor response. A basic understanding of the
      different responses of various species to these inhaled toxins will contribute to
      our understanding of the mechanisms involved in human disease.

PMID- 11570673
TI  - Cellular and molecular mechanisms regulating silica-induced adhesion molecule
      expression in mice.
AB  - Exposure of mice to silica particles generates an intense inflammatory response
      characterized by the influx of neutrophils and monocytes into the alveoli with
      resulting cell activation. These cell trafficking and effector functions are, in
      part, mediated by different families of adhesion molecules. One such adhesion
      protein, intercellular adhesion molecule-1 (ICAM-1), is expressed on a variety of
      cells including vascular endothelial cells, fibroblasts, types I and II alveolar
      epithelial cells, some lymphocytes, and monocytes/macrophages. Over the last
      several years, our laboratory has focused on silica-induced ICAM-1 expression in
      exposed mice (in vivo) and cells (in vitro) by examining the role and regulation
      of this adhesion protein on pulmonary cells. We have determined that
      intratracheal exposure of mice to silica (2 mg per mouse) elicits increased
      expression of ICAM-1 on pulmonary macrophages and type II epithelial cells within
      the lung parenchyma, on bronchoalveolar lavage macrophages, and as a soluble
      protein in lavage fluid. We hypothesize that increased ICAM-1 expression
      mayparticipate in silica-induced neutrophil influx into the alveoli, as well as
      in macrophage-derived phlogistic signals responsible for migration of
      neutrophils. ICAM-1 expression on silica-exposed mouse macrophages is enhanced by
      reactive oxygen species (ROS) and tumor necrosis factor-alpha (TNF-alpha) and
      appears to be regulated through specific sequence elements within the ICAM-1
      promoter.

PMID- 11570674
TI  - Lymphocytes, lymphokines, and silicosis.
AB  - Silicosis is characterized by mononuclear cell aggregation with mineral particles
      and fibrosis. Lymphocytes are abundant in these lesions. We exposed inbred
      strains of mice to a respirable aerosol of cristobalite silica (70 mg/m3, 5 h/d,
      12 d) or shamair. Silicosis evolved over months after exposure. The silica
      exposed mice showed the accumulation of lymphocytes in alveolar spaces (seen in
      bronchoalveolar lavage), in lung parenchymal lesions and nodules, and in enlarged
      bronchial-associated lymphoid tissues and thoracic lymph nodes. The lung
      lymphocytes were predominantly CD4+ T cells, but numerous CD8+ T cells, natural
      killer cells, and CD4- gammadelta-TCR+ T cells were present as well. Interferon
      gamma (IFN-gamma) production was upregulated, suggesting a THelper-1-like
      response in silicosis. In silicotic lung tissue, mRNA transcripts for the
      macrophage-derived cytokines IL-12 and -18 were increased. IFN-gamma gene-deleted
      mice (C57Bl/6-Ifngtm1 Ts) exposed to silica developed less extensive silicosis
      and less lung collagen accumulation than wild-type mice. We hypothesize that
      there is a reiterative amplification cycle in which macrophages with silica may
      produce cytokines, such as IL-12 and -18, that attract and activate lymphocytes.
      These activated lymphocytes may then produce additional mediators that in turn
      attract and activate an expanded secondary population of macrophages. IFN-gamma
      would be a likely cause of macrophage activation in this cycle. More work is
      needed to understand the biological events that lead from the inhaled dust to the
      scarred lung, and to clarify the role of lymphocytes in this process.

PMID- 11570675
TI  - IgG subclass responses in experimental silicosis.
AB  - Silicosis is a crippling fibrotic lung disease induced by inhaling crystalline
      silica. In addition to fibrosis, silica inhalation by humans is associated with a
      number of immunological effects including increased levels of serum
      immunoglobulins (in particular IgG), increased prevalence of autoantibodies, and
      autoimmune disease. Recent studies using rodent models have shown that
      experimental silicosis is associated with a T-helper (TH)1 pattern of T-cell
      activation in the lungs and lung-associated lymph nodes after silica inhalation,
      which are also the sites of increased IgG production. We therefore hypothesized
      that the subclass distribution of IgG production occurring in experimental
      silicosis would suggest TH1 activation as the primary stimulus for IgG
      production. Using an ELISPOT assay, we found increased IgG-secreting spot-forming
      cells of all IgG subclasses in lung-associated lymph nodes taken from silica
      exposed rats 3 to 4 months after aerosol exposure to silica. Neither TH1- nor TH2
      dependent IgG subclass-secreting cells were selectively enhanced. Our findings
      suggest that TH1 activation alone does not account for increased production of
      IgG in experimental silicosis.

PMID- 11570676
TI  - Silica and PM1648 modify human alveolar macrophage antigen-presenting cell
      activity in vitro.
AB  - Some inhaled particles are known to lead to inflammation and lung pathology,
      whereas others do not appear to have long-term effects. Potential mechanisms to
      account for these differences are only beginning to be understood. In this
      article we examine whether silica and PM1648 (a model urban particulate) caused
      selective deletion of the suppressor human alveolar macrophage (HAM) phenotype
      (RFD1+/7+), and whether this affected cytokine production in an antigen
      presenting cell (APC) assay with autologous T lymphocytes. HAM were exposed to
      the bioactive particulates, silica and PM1648, for 24 hours, then isolated free
      of extracellular particulates and nonviable cells; HAM were then cultured with
      autologous lymphocytes in an 11-day APC assay. Silica exposure up-regulated a TH1
      lymphocyte-derived cytokine, interferon gamma (IFN-gamma), and a TH2 lymphocyte
      derived cytokine, interleukin-4 (IL-4). PM1648 exposure primarily upregulated IL
      4. Neither particle exposure had a significant effect on interleukin-10 (IL-10)
      production. Control particulate exposures with titanium dioxide (TiO2) and
      wollastonite (Woll) caused no altered APC activity. Silica and PM1648
      demonstrated selective toxicity to suppressor macrophages (RFD1+/7+). We propose
      that, because of the suppressor macrophage phenotype disabling, the activator
      macrophage (RFD1+/7-) operates free of the suppressor macrophage's influence,
      enhancing APC activity with increased lymphocyte-derived proinflammatory cytokine
      production.

PMID- 11570677
TI  - Reactive oxygen species and molecular mechanism of silica-induced lung injury.
AB  - Silica particles are considered to be fibrogenic and carcinogenic agents, but the
      mechanisms of disease initiation and progression are not fully understood. This
      article summarizes the literature on the generation of reactive oxygen species
      (ROS) directly from interaction of silica with aqueous medium and from silica
      stimulated cells. This article also discusses the role of ROS in silica-induced
      lung injury, with particular focus on the silica-induced NF-kappaB activation,
      including the molecular mechanisms of its regulation, its possible attenuation,
      and its relationship to silica-induced generation of cyclooxygenase II and TNF
      alpha.

PMID- 11570678
TI  - Variability of biological responses to silicas: effect of origin, crystallinity,
      and state of surface on generation of reactive oxygen species and morphological
      transformation of mammalian cells.
AB  - Variously modified quartz dusts and one amorphous diatomaceous earth have been
      compared in their potential to release HO* radicals and in their activity in the
      Syrian hamster embryo (SHE) cell transformation assay. Both original dusts, made
      up by well-crystallized quartz particles, or by mostly amorphous, variously
      shaped, silica particles, were active in HO* release, were cytotoxic, and induced
      morphological transformation in SHE cells. The cristobalite dust, obtained by
      heating quartz above the phase transition temperature, lost any activity in free
      radical release, cytotoxicity, and transforming potency. Surface-modified quartz
      dusts were obtained by a mild etching with HF, by depriving the surface of trace
      iron with deferoxamine, or by enriching it with iron. The chemical and biological
      activity decreased in all cases. Both iron-deprived and iron-enriched quartz were
      nearly inactive. A linear correlation was found between the amount of HO*
      released by the particles and the transformation frequency. When the SHE cell
      assay was performed in the presence of mannitol or antioxidant enzymes
      (superoxide dismutase [SOD] or catalase), the number of transformed cells
      markedly decreased. This effect was more pronounced for catalase and mannitol
      than for SOD. HO* release was reduced, but not suppressed, by deferoxamine. All
      the above results are consistent with the presence of two kinds of surface sites
      active in HO* release and cell transformation: (1) silicon-based radicals,
      abundant on freshly ground dusts, which generate the HO* radicals without the
      superoxide ion as intermediate; and (2) isolated iron centers where the Haber
      Weiss cycle takes place, with the superoxide ion as intermediate. The activities
      of both sites are inhibited by mannitol or catalase, whereas only the last one is
      inhibited by SOD.

PMID- 11570679
TI  - A world without adhesion?

PMID- 11570680
TI  - The influence of relative humidity on the effect of dentin bonding systems.
AB  - PURPOSE: The aim of the study was to measure the influence of relative humidity
      of the ambient air on bond strength to enamel and dentin of six different bonding
      systems. In this manner, the role of the primer solvent was assessed. MATERIALS
      AND METHODS: The bonding systems selected were Prime & Bond 2.1, One Step,
      Scotchbond MP, Syntac Single Component, Optibond Solo, and Perma Quick. The
      primers of these systems are based on either acetone, water or ethanol. Plane
      enamel and dentin surfaces were placed at relative humidities of 18%, 45%, 80% or
      99% RH and then treated in accordance with the recommendations of the respective
      manufacturers. A resin composite was then bonded to the treated surfaces. After
      storage in water at 37 degrees C for 1 day, the bonded specimens were broken in
      shear. RESULTS: The bonds to enamel were either unaffected or in one case
      moderately increased by increasing ambient humidity. The bonds to dentin were
      either unaffected or in four cases strongly reduced by increasing humidity.
      CONCLUSIONS: The response of the bonding systems to differences in ambient
      humidity were not related to the solvent of the primer in a simple way. To
      exclude the damaging effect of high humidity on dentin bonding, the use of rubber
      dam is recommended.

PMID- 11570681
TI  - Microtensile bond strength of two single-step adhesive systems to bur-prepared
      dentin.
AB  - PURPOSE: To compare the microtensile bond strength (MTBS) of two single-step
      adhesive systems to two types of bur-prepared dentin. MATERIALS AND METHODS:
      Using either of two adhesives, the experimental MZ-2000 (MZ) and the commercial
      One-Up Bond F (OUB), resin composite was bonded to flat buccal and root dentin
      surfaces of eight extracted human premolars. These surfaces were produced by
      grinding with either regular-grit or superfine-grit diamond burs in a high-speed
      handpiece. After storage overnight in 37 degrees C water, the bonded specimens
      were sectioned into ten slices approximately 0.7 mm thick, perpendicular to the
      bonded surface. They were then subjected to microtensile testing. The surfaces of
      the fractured specimens were observed both visually and microscopically to
      determine the failure mode. In addition, to observe the effect of conditioning,
      the two types of bur-ground dentin surfaces were conditioned with the adhesives,
      rinsed with acetone, and observed under SEM. RESULTS: When MZ was bonded to
      dentin prepared with a regular-grit diamond bur, MTBS was the lowest and failures
      occurred adhesively at the interface, whereas other groups revealed primarily
      mixed failures. MZ-conditioned dentin surfaces ground with a regular-grit diamond
      bur were covered with a residual smear layer. However, the smear layers on the
      surface of MZ-conditioned dentin ground with a superfine-grit diamond bur and on
      OUB-conditioned dentin prepared either with a regular-grit or superfine-grit
      diamond bur were mostly or partially dissolved. CONCLUSION: Some of the single
      step adhesive systems may produce low bond strengths to smear layers created by
      regular-grit diamond burs.

PMID- 11570682
TI  - Effects of demineralization depth on microtensile bond strength to human dentin.
AB  - PURPOSE: To evaluate the effect of different phosphoric acid concentrations (10%
      and 37%) on the microtensile bond strengths (microTBS) of three dentin adhesive
      systems with different solvents (ethanol, acetone, or none). MATERIALS AND
      METHODS: Eighteen third molars divided into six groups were ground flat to expose
      superficial dentin, which was polished to 600-grit. The bonding procedure was
      initiated using either of two phosphoric acid gels (10% and 37%). Three adhesive
      systems - Single Bond (SB), Prime & Bond NT (NT), and One Coat Bond (OC) - with
      different solvents (ethanol, acetone, or none, respectively) were used. After
      adhesive application, a cylinder of composite resin was built up. After 24 h
      water storage, each tooth was serially sectioned into thin rectangular sections
      (or "sticks") parallel to the long axis and with a mean cross-sectional area of
      0.4 mm2. microTBS were determined using an Instron universal testing machine.
      Data were analyzed using two-way ANOVA and Duncan's test. RESULTS: Mean bond
      strengths ranged from 66.1 MPa for 10%/ H3PO4 and SB to 43.8 MPa for 37% H3PO4
      and OC. SB and OC tended to have slightly higher bond strengths when 10% H3PO4
      was used. NT with 37% H3PO4 had a significantly higher microTBS (54.6 MPa) than
      NT with 10% H3PO4 (44.4 MPa). CONCLUSION: Etching dentin with 37% H3PO4 resulted
      in a significantly higher mean microTBS for the acetone-based adhesive NT. For
      both the ethanol- and water-based adhesive (SB) and the solvent-free adhesive
      (OC), acid concentration did not significantly affect bond strength.

PMID- 11570683
TI  - Bonding strength to two different surfaces of dentin under simulated pulpal
      pressure.
AB  - PURPOSE: The purpose of this in vitro study was to measure and compare the in
      vitro shear bond strengths (SBS) of the following dentin bonding systems to
      different dentin surfaces under simulated pulpal pressure: Liner Bond 2 (self
      etching) (LB2), Liner Bond 2V (self-etching) (LB2V), Opti Bond Solo (single
      component) (OBS), Fuji Bond LC (filled) (FBLC), Prime & Bond 2-1 (single
      component) (P&B2-1), and Solid Bond (total etching) (SB). MATERIALS AND METHODS:
      Occlusal and buccal surfaces of 60 extracted human molars were prepared to expose
      the dentin bonding surface. After being wet ground with 600-grit abrasive papers,
      teeth were randomly assigned to 6 equal groups of 10 each. The dentin surfaces
      were treated with the bonding systems mentioned above, and resin composite
      cylinders (Clearfil AP-X) were built up under simulated pulpal pressure when
      diluted bovine serum was used as the pulpal fluid. After one day of storage in 37
      degrees C water, the specimens were shear tested to failure on an Instron
      machine. RESULTS: The data were statistically analyzed with the Student's t-test
      and a post hoc Tukey test. Comparing buccal surfaces, the post hoc Tukey test
      indicated no significant differences among all the test groups (p > 0.05). On
      occlusal surfaces, the post hoc Tukey test indicated significant differences
      among the tested groups (p < 0.05). The Student's t test revealed significant
      differences between the occlusal and buccal shear bond strength values in LB 2,
      LB2V, and SB groups (p < 0.05). CONCLUSION: The strength of adhesion to dentin
      depends upon both the adhesive system used - with self-etching systems tending to
      show higher bond strengths than the other materials tested - and the location of
      the dentin, with significantly higher SBS being found on buccal surfaces in 3 of
      the 7 tested bonding systems.

PMID- 11570684
TI  - Effect of different conditioning protocols on adhesion of a GIC to dentin.
AB  - PURPOSE: This study examined the ultrastructure and microtensile bond strength
      (microTBS) of a restorative glass-ionomer cement (GIC; Dentsply) to sound dentin
      that was conditioned with various techniques. MATERIALS AND METHODS: Dentin
      surfaces from extracted human third molars were abraded with 180-grit SiC paper.
      Five groups of three teeth each were prepared: C - no acid pretreatment
      (control); P - 10% polyacrylic acid (PAA) for 10 s, no rinsing; R - 10% PAA for
      20 s, rinsed; K - 25% PAA for 25 s, rinsed; and H -32% phosphoric acid for 15 s,
      rinsed. TEM was performed on a bonded specimen from each group, using unstained,
      undemineralized sections. GIC buildups were made on the remaining teeth, and
      after storage at 100% humidity for 24 h, the teeth were sectioned for microTBS
      and SEM evaluation. RESULTS: TEM revealed the presence of a structure known as
      the intermediate layer in all groups. This layer contains metallic salts
      contributed by both the GIC and dentin. In group C, this layer was restricted to
      the smear layer. In groups P and R, intermediate layers could be found above
      partially demineralized zones within the intertubular dentin. In groups
      conditioned with more aggressive protocols (K and H), the intermediate layers
      shifted downward to reside within the superficial portions of completely
      demineralized collagen. Group C had statistically lower microTBS (p < 0.05),
      while the other groups were not significantly different from each other. SEM
      revealed adhesive failures along the dentin surface in group C and mixed failures
      in the other groups. CONCLUSION: The lower microTBS observed in the control group
      reflects the weakness of the smear layer attachment to dentin. The higher
      microTBS in the other groups probably represent the cohesive strength of GIC
      under tension, rather than its true adhesive strength to dentin. Acid
      pretreatment dissolves the smear layer, creates a zone of partially demineralized
      dentin, and allows the PAA to interact with dentin via the intermediate layer.
      Overly aggressive conditioning renders the dentinal tubules patent, and leaves
      deeper demineralized dentin that does not form part of the intermediate layer.

PMID- 11570685
TI  - Influence of rubber-dam on the reconstruction of proximal contacts with adhesive
      tooth-colored restorations.
AB  - PURPOSE: To clinically measure the influence of rubber-dam on the proximal
      contact strength after its reconstruction with tooth-colored restorations.
      MATERIALS AND METHODS: The frictional forces during the removal of a metal strip
      from the proximal contact area were taken as measure for the proximal contact
      strengths of 46 restorations (35 ceramic inlays, 11 direct composite
      restorations). The teeth were separated with a rubber-dam and wedged thoroughly
      during the complete reconstruction procedure according to the multiple wedging
      technique. The proximal contact strengths were measured immediately before and
      immediately after removing the rubber-dam. RESULTS: The contact strengths were
      statistically significantly lower immediately after the removal of the rubber-dam
      (1.07+/-0.82N) compared to the situation with the rubber-dam (1.99+/-1.21N). The
      amount of the reduction after removing the rubber-dam was statistically
      significantly higher between the second premolar and the first molar (1.45+/
      1.06N) compared to the contacts between the canines and the first premolar
      (0.32+/-0.44N) and the first and second premolar (0.59+/-0.77N). No influence of
      the restorative material, the use and localization of retainers, localization of
      the restoration, or number of teeth under the rubber-dam was detectable.
      CONCLUSION: Rubber-dam is recommended for adhesive restorations as it is helpful
      for achieving good adhesion between the tooth and restorative materials.
      Nevertheless, the application of rubber-dam seems to be a factor which
      complicates the reconstruction of adequate proximal contacts.

PMID- 11570686
TI  - The effects of bonding system and light curing method on reducing stress of
      different C-factor cavities.
AB  - PURPOSE: The effect of the slow-start curing method on the marginal sealing and
      cavity wall adaptation on resin composite restorations with different C-factors
      was evaluated. METHODS: Cylindrical cavities, 1 mm deep and 3 mm in diameter (C
      factor=2.3) or 2 mm in diameter (C-factor=3) were prepared on flat superficial
      bovine dentin surfaces. The teeth were restored with Clearfil Photo Bond,
      Clearfil Liner Bond 2 or Super-Bond D Liner adhesive systems followed by Photo
      Clearfil Bright composite. The resins were cured with a conventional method using
      600 mW/cm2 (tip-to-resin distance 0 mm) for 60 s, or the slow-start curing method
      of 270 mW/cm2 (tip-to-resin distance 10 mm) for 10 s, followed by a 5-s interval,
      then 50 s at 600 mW/cm2. After thermocycling, a dye penetration test was carried
      out. The dye penetration length was calculated as a percentage of the total
      cavity wall length. RESULTS: Cavity-wall gap formation increased when the C
      factor increased from 2.3 to 3, except in one material, Super-Bond D Liner, which
      showed good marginal sealing and resin composite adaptation to the cavity wall
      regardless of light curing method and C-factor. CONCLUSION: It is necessary to
      take care when a cavity with a high C-factor is to be restored with resin
      composite. The combination of a flexible adhesive and the slow-start curing
      method would seem to be effective in reducing polymerization contraction stress
      for large C-factor cavities.

PMID- 11570687
TI  - Clinical evaluation of posterior composite restorations: the 10-year report.
AB  - PURPOSE: To summarize all clinically relevant data of a 10-year prospective
      evaluation of posterior glass-ionomer cement/composite restorations (Ketac
      Bond/Visio-Molar radiopaque). MATERIAL AND METHODS: For this study 194 hybrid
      composite fillings (115 Class I, 79 Class II) were applied in 73 adult patients.
      The exposed dentin was covered with glass-ionomer cement. The clinical evaluation
      was carried out at baseline, after 6 months and at 1-year intervals up to 10
      years. The USPHS-compatible CPM Index was used with the C and P criteria
      presented here for anatomic form, color match, surface quality, wear, marginal
      integrity, marginal ledge, marginal discoloration, secondary caries, and clinical
      acceptability. Thermal and electrical sensitivity testing were recorded annually.
      RESULTS: At baseline, 194 restorations were rated. The drop-out of patients
      comprised 108 fillings after 10 years. During this time, 24 restorations could
      not be followed up because of new carious lesions at different sites and/or
      prosthodontic treatment (drop-out of teeth). Forty-six composite restorations
      were longitudinally controlled over 10 years, and 16 more fillings failed before
      the end of the study (3 filling fractures, 7 partial filling losses, 1 total
      filling loss, 5 cases of secondary caries). Only Class II composite restorations
      exhibited secondary caries (4 fillings after 7 years and 1 filling after 9
      years). After 10 years, the correct anatomic form was preserved in 44 fillings,
      but all restorations showed rough surface and wear. The majority of restorations
      (26 fillings) was free of marginal discoloration, and the color match showed only
      3 fillings being too dark. The marginal integrity was optimal at baseline and
      during the first year. During the second year a continuing degradation started
      and lasted until the end of the study. Thirteen restorations showed optimal
      marginal integrity after 10 years. CONCLUSION: The USPHS-compatible CPM Index
      represents a sensitive rating system for long-term observation of posterior
      composite restorations. The early risk of failure is attributed to bulk fractures
      and partial loss of filling material. The longevity over 10 years is a maximum of
      74.2%, and the very low secondary caries rate and the high percentage of correct
      anatomical form confirm the clinical safety of posterior composite restorations.

PMID- 11570688
TI  - Cadmium-induced apoptosis in murine fibroblasts is suppressed by Bcl-2.
AB  - We investigated the induction of apoptosis by cadmium in NIH 3T3 murine
      fibroblasts. Apoptosis was triggered effectively by 10 microM CdCl2 within 24 h,
      under which conditions cell viability was reduced by 50%. Cadmium-induced
      apoptosis was demonstrated by both morphological and biochemical analysis. We
      have shown that cadmium concentrations of 5-20 microM caused nuclear
      fragmentation. Moreover, internucleosomal DNA fragmentation was evoked by 10-25
      microM CdCl2 within 24 h, as detected by the formation of ladder patterns in DNA
      electrophoresis. Since the induction of programmed cell death occurs together
      with modifications in the cell cycle, we examined the ability of cadmium to block
      cell divisions by using a 5-bromo2-deoxy-uridine incorporation assay. Our results
      indicate that about 40% of treated cells are blocked in G0-G1 phase when exposed
      to 10 microM cadmium for 27 h. Finally, we addressed the question of whether the
      effect of cadmium could be prevented by suppressing apoptosis. Over-expression of
      the anti-apoptotic protein Bcl-2 in NIH 3T3 cells protects against cadmium
      toxicity, thus suggesting a role for Bcl-2 in the regulation of cadmium-induced
      apoptosis.

PMID- 11570689
TI  - Effects of local blood flow on the percutaneous absorption of the
      organophosphorus compound malathion: a microdialysis study in man.
AB  - Malathion [O,O-dimethyl-S-(1,2-dicarbethoxyethyl)phosphorodithioate] is an
      organophosphorus insecticide widely used in veterinary medicine and in humans for
      the treatment of lice. In this study, the rate of the percutaneous absorption of
      malathion has been measured in human skin, in vivo, using microdialysis.
      Malathion was detected in tissue dialysate within 30 min of its topical
      application to the skin of the volar surface of the forearm of healthy
      volunteers. The concentration of malathion in dialysate increased with
      lengthening duration of exposure to reach a steady state concentration at 2 h.
      Prolonged exposure to malathion caused a marked and long-lasting erythema
      localized to the area of contact. There was no evidence of local tissue oedema or
      of a neurogenically mediated flare or itch response following topical
      application. Reducing skin blood flow by the addition of the vasoconstrictor
      noradrenaline to the dialysis probe perfusate caused an eight-fold increase in
      the recovery of malathion in the dialysate, which failed to reach a steady state
      within 5 h. Together, these data confirm that malathion can be absorbed
      percutaneously and that its distribution within the cutaneous tissue space is
      influenced by local skin blood flow. They suggest that the increase in skin blood
      flow caused by malathion may itself play a significant role in enhancing its
      systemic uptake.

PMID- 11570690
TI  - Mixture component effects on the in vitro dermal absorption of pentachlorophenol.
AB  - Interactions between chemicals in a mixture and interactions of mixture
      components with the skin can significantly alter the rate and extent of
      percutaneous absorption, as well as the cutaneous disposition of a topically
      applied chemical. The predictive ability of dermal absorption models, and
      consequently the dermal risk assessment process, would be greatly improved by the
      elucidation and characterization of these interactions. Pentachlorophenol (PCP),
      a compound known to penetrate the skin readily, was used as a marker compound to
      examine mixture component effects using in vitro porcine skin models. PCP was
      administered in ethanol or in a 40% ethanol/60% water mixture or a 40%
      ethanol/60% water mixture containing either the rubefacient methyl nicotinate
      (MNA) or the surfactant sodium lauryl sulfate (SLS), or both MNA and SLS.
      Experiments were also conducted with 14C-labelled 3,3',4,4'-tetrachlorobiphenyl
      (TCB) and 3,3',4,4',5-pentachlorobiphenyl (PCB). Maximal PCP absorption was
      14.12% of the applied dose from the mixture containing SLS, MNA, ethanol and
      water. However, when PCP was administered in ethanol only, absorption was only
      1.12% of the applied dose. There were also qualitative differences among the
      absorption profiles for the different PCP mixtures. In contrast with the PCP
      results, absorption of TCB or PCB was negligible in perfused porcine skin, with
      only 0.14% of the applied TCB dose and 0.05% of the applied PCB dose being
      maximally absorbed. The low absorption levels for the PCB congeners precluded the
      identification of mixture component effects. These results suggest that dermal
      absorption estimates from a single chemical exposure may not reflect absorption
      seen after exposure as a chemical mixture and that absorption of both TCB and PCB
      are minimal in this model system.

PMID- 11570691
TI  - Expression of cytochrome P450 2E1 in normal human bronchial epithelial cells and
      activation by ethanol in culture.
AB  - Serum-free primary cultures of human bronchial epithelial cells and freshly
      isolated samples of human bronchial epithelium were used to investigate basal
      expression of the cytochrome P450 enzyme CYP2E1 and its activation or induction
      by ethanol in bronchial epithelial cells. The cultures consisted of > or =95%
      cells of epithelial characteristics as determined by transmission electron
      microscopy and immunohistochemical staining. Monolayers were obtained from
      explants over a period of several months via transfer of tissue into new dishes
      ('generations'1-5). Using RT-PCR analysis, basal expression of mRNAs coding for
      CYP2B7, CYP2F1 and CYP2E1 were detected in cultures from several donors. The
      basal expression of CYP2E1 protein and mRNA showed differences between the
      donors. The mRNA was detected even in cultures from higher generations and
      increased in some cultures over time. The CYP2E1 protein content was low and in
      most cultures of generations 2-5 could not be detected by immunoblot analysis of
      native protein extracts. Nevertheless, in some cases immunoreactive CYP2E1
      protein was present in monolayers obtained from the fourth and fifth transfer (18
      week 'generation'). CYP2E1 activity was measured via 6-hydroxylation of
      chlorzoxazone either by a destructive assay using cell lysate or by a non
      invasive assay using the medium of cell cultures. In short-term cultured isolated
      bronchial epithelium, ethanol treatment increased CYP2E1 activity by up to 5-fold
      within 4 days but with inter-individual differences. In cells up to 4 weeks in
      culture, CYP2E1 activity remained inducible by a single dose of ethanol.
      Differentiated primary human cells in culture may be useful tools as model
      systems for the evaluation of CYP2E1-driven processes in man.

PMID- 11570692
TI  - Nitric oxide modulates high-energy phosphates in brain regions of rats
      intoxicated with diisopropylphosphorofluoridate or carbofuran: prevention by N
      tert-butyl-alpha-phenylnitrone or vitamin E.
AB  - Acute effects of seizure-inducing doses of the organophosphate compound
      diisopropylphosphorofluoridate (DFP, 1.25 mg/kg s.c.) or the carbamate
      insecticide carbofuran (CF, 1.25 mg/kg s.c.) on nitric oxide (NO) were studied in
      the brain of rats. Brain regions (pyriform cortex, amygdala, and hippocampus)
      were assayed for citrulline as the determinant of NO and for high-energy
      phosphates (ATP and phosphocreatine) as well as their major metabolites (ADP,
      AMP, and creatine). Rats, anesthetized with sodium pentobarbital (50 mg/kg i.p.),
      were killed using a head-focused microwave (power, 10 kW; duration, 1.7 s).
      Analyses of brain regions of controls revealed significantly higher levels of
      citrulline in the amygdala (289.8+/-7.0 nmol/g), followed by the hippocampus
      (253.8+/-5.5 nmol/g), and cortex (121.7+/-4.3 nmol/g). Levels of energy
      metabolites were significantly higher in cortex than in amygdala or hippocampus.
      Within 5 min of CF injection, the citrulline levels were markedly elevated in all
      three brain regions examined, while with DFP treatment, only the cortex levels
      were elevated at this time. With either acetylcholinesterase (AChE) inhibitor,
      the maximum increase in citrulline levels was noted 30 min post-injection (> 6-
      to 7-fold in the cortex, and > 3- to 4-fold in the amygdala or hippocampus).
      Within 1 h following DFP or CF injection, marked declines in ATP (36-60%) and
      phosphocreatine (28-53%) were seen. Total adenine nucleotides and total creatine
      compounds were reduced (36 58% and 28-48%, respectively). The inverse
      relationship between the increase in NO and the decease in high-energy
      phosphates, could partly be due to NO-induced impaired mitochondrial respiration
      leading to depletion of energy metabolites. Pretreatment of rats with an
      antioxidant, the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN, 200
      mg/kg i.p.), prevented DFP- or CF-induced seizures, while the antioxidant vitamin
      E (100 mg/kg i.p. per day for 3 days) had no anticonvulsant effect. Both
      antioxidants, however, significantly prevented the increase of citrulline and the
      depletion of high-energy phosphates. It is concluded that seizures induced by DFP
      and CF produce oxidative stress due to a marked increase in NO, causing
      mitochondrial dysfunction, and thereby depleting neuronal energy metabolites. PBN
      pretreatment provides protection against AChE inhibitor-induced oxidative stress
      mainly by preventing seizures. Additional antioxidant actions of PBN may
      contribute to its protective effects. Vitamin E has direct antioxidant effects by
      preventing excessive NO production.

PMID- 11570693
TI  - Mouse hepatocyte response to peroxisome proliferators: dependency on hepatic
      nonparenchymal cells and peroxisome proliferator activated receptor alpha
      (PPARalpha).
AB  - Peroxisome proliferators (PPs) are rodent nongenotoxic hepatocarcinogens that
      induce peroxisome proliferation and DNA synthesis, and suppress apoptosis in
      rodent hepatocytes. PPs act through the PP-activated receptor alpha (PPARalpha);
      tumour necrosis factor alpha (TNFalpha) and hepatic nonparenchymal cells (NPCs),
      the major source of TNF alpha in the liver, have also been implicated in
      mediating the rodent hepatic response to PPs. Here we investigate the interaction
      between PPARalpha and NPCs in regulating the response to PPs. Using normal
      hepatocyte cultures containing around 20% NPCs, the PP nafenopin (50 microM)
      induced DNA synthesis and suppressed transforming growth factor beta1-induced
      apoptosis. However, when the NPCs were removed by differential centrifugation,
      nafenopin did not induce DNA synthesis or suppress apoptosis in the pure
      hepatocytes. Reconstitution of the normal hepatocyte cultures by mixing together
      the pure hepatocytes and the previously separated NPCs in the same proportions as
      the original cell preparation (17.7+/-8.7% NPCs) restored the response to
      nafenopin. Interestingly, nafenopin was still able to induce beta-oxidation in
      the pure hepatocyte cultures, consistent with NPCs being required for PP-induced
      growth but not for peroxisome proliferation. Next, we evaluated the role of
      PPARalpha in the hepatocyte dependency upon NPCs. Interestingly, NPCs isolated
      from PPARalpha-null mice, like those isolated from the wild-type NPCs, restored
      the hepatocyte response to nafenopin. However, as expected, PPARalpha-null
      hepatocytes remained non-responsive to PPs, irrespective of the genotype of the
      added NPCs. These data support a role for NPCs in facilitating a response of
      hepatocytes to PPs that is ultimately dependent on the presence of PPARalpha in
      the hepatocyte.

PMID- 11570694
TI  - Disrupted carbonic anhydrase distribution in the avian shell gland following in
      ovo exposure to estrogen.
AB  - Eggshell thinning among wild birds has been an environmental concern for almost
      half a century and the underlying mechanisms are still not fully understood.
      Previously we showed that exposure of quail embryos to ethynylestradiol (EE2)
      caused disorganization of the tubular glands in the shell gland of adult birds.
      In this study, we have examined the effect of in ovo exposure to EE2 on carbonic
      anhydrase (CA) localization, especially in the shell gland, because CA is
      required for shell formation. In the control birds, CA was localized in the cell
      membranes of the tubular gland cells of the shell gland, whereas the surface
      epithelium was always devoid of CA. In ovo treatment with 20ng EE2/g egg resulted
      in a loss of CA activity in the tubular glands while the surface epithelium
      showed strong induction of both membrane bound and cytoplasmic CA activity in
      49+/-1% of the cells. The dose 2ng EE2/g egg resulted in partial loss of tubular
      gland CA and strong induction of CA activity in 2.5+/-0.5% of the surface
      epithelial cells and weaker induction in 22+/-2% of the epithelial cells. In
      conclusion, this study shows that embryonic exposure to a xenoestrogen disrupts
      CA distribution in the adult shell gland. We propose that eggshell thinning in
      avian wildlife could reflect a functional malformation in the shell gland,
      already induced by xenoestrogen during embryonic development rather than being
      caused solely by exposure of the adult bird.

PMID- 11570696
TI  - Cumulative exposure to tamoxifen: DNA adducts and liver cancer in the rat.
AB  - Tamoxifen is a potent rat liver carcinogen, currently being used as a long-term
      chemopreventative for breast cancer in healthy women. The mechanism by which
      tamoxifen causes liver cancer in rats is known to be associated with the
      accumulation of tamoxifen DNA adducts in this organ. We have examined the dose
      response relationship of tamoxifen-induced DNA adducts in the liver and the
      subsequent increase in the development of liver cancer, with and without
      phenobarbital promotion. Female Wistar (Han) rats were fed 420 ppm tamoxifen in
      the diet for 0, 1, 4, 8 or 12 weeks after which time rats were either examined
      immediately for hepatic tamoxifen-induced DNA damage using the 32P-Postlabelling
      assay, or left for lifetime for tumour assessment. A proportion of rats left for
      lifetime study were given phenobarbital in their drinking water. There was a
      clear dose-response relationship with respect to duration of tamoxifen exposure
      for both accumulation of DNA adducts and lifetime risk of liver cancer. In the
      absence of phenobarbital promotion there was a threshold value for tamoxifen
      induced DNA adducts (180 adducts/10(8) nucleotides) and the subsequent induction
      of liver cancer. This study demonstrates the relationship between the
      accumulation of hepatic tamoxifen-induced DNA adducts and the development of
      liver cancer and establishes the threshold for hepatocarcinogenesis in terms of
      DNA adduct formation. These data could provide useful information in interpreting
      the relevance of low levels of DNA adducts in humans.

PMID- 11570695
TI  - Biochemical changes in Achilles tendon from juvenile dogs after treatment with
      ciprofloxacin or feeding a magnesium-deficient diet.
AB  - Quinolones are antibacterial agents that have the potential to induce Achilles
      tendon disorders - such as tendinitis or even ruptures - in patients treated with
      these drugs. We studied the effects of ciprofloxacin on several proteins of
      Achilles tendons from immature dogs, 10- to 11-weeks-old. The dogs were treated
      orally for 5 days with 30 or 200 mg ciprofloxacin/kg body weight or with the
      vehicle alone. Since quinolone-like alterations in joint cartilage were observed
      in magnesium-deficient animals, another group was fed a magnesium-deficient diet
      for 6 weeks. At necropsy, tendons (n=3 from each group) were frozen and stored
      until analysis when they were homogenized in a lysis buffer to release a soluble
      fraction of the tendon proteins. Densitometric analysis of the immunoblots with
      anticollagen type I, anti-elastin, anti-fibronectin, and antiintegrin antibodies
      showed a significant reduction of all proteins. For example, collagen type I
      concentrations (mean +/-SD, arbitrary densitometric units) were 3190+/-217
      (controls), 1890+/-468 (30mg/kg), 1695+/-135 (200mg/kg) and 2053+/-491 in the
      magnesium-deficient dogs. The differences between concentrations in controls and
      all treated groups were statistically significant (P<0.01, t-test). Similarly,
      compared with control samples, relative concentrations of other proteins in
      tendons from ciprofloxacin-treated dogs (30 mg/kg) decreased by 73% (elastin),
      88% (fibronectin), and 96% (beta1 integrin) (data from low-dose group only). A
      very similar pattern of protein alterations was detected in samples from
      magnesium-deficient dogs. In conclusion, rather low doses of a fluoroquinolone or
      a diet-induced magnesium deficiency caused similar biochemical alterations in the
      soluble fraction of proteins from canine tendons. These findings support our
      hypothesis that quinolone-induced toxic effects on connective tissue structures
      are due to the magnesium-antagonistic effects of these antibacterial agents. They
      also indicate that patients with a latent magnesium deficiency could be at an
      increased risk of quinolone-induced tendon disorders.

PMID- 11570697
TI  - Identification of CNS neurons involved in the innervation of the epididymis: a
      viral transneuronal tracing study.
AB  - Cell groups of the spinal cord and the brain transsynaptically connected with the
      epididymis (caput, cauda) were identified by means of the viral transneuronal
      tracing technique. Pseudorabies virus was injected into the caput or the cauda
      epididymidis, and after survival times 4 and 5 days, the spinal cord and brain
      were processed immunocytochemically. Virus-labeled neurons could be detected in
      the preganglionic sympathetic neurons (lower thoracic and upper lumbar segments)
      and following virus injection into the cauda epididymidis, also in the sacral
      parasympathetic nucleus (L6-S1). Virus-infected perikarya were present in several
      brain stem nuclei (lateral reticular nucleus, gigantocellular and
      paragigantocellular nucleus, A5 noradrenergic cell group, caudal raphe nuclei,
      locus coeruleus, Barrington's nucleus, nucleus of the solitary tract,
      periaqueductal gray) and in the diencephalon (hypothalamic paraventricular
      nucleus, lateral hypothalamus). At the longer survival time, some telencephalic
      structures also exhibited virus-labeled neurons. The distribution of infected
      neurons in the brain was similar after virus injection into the caput or cauda
      epididymidis; however, earlier onset of infection was observed after inoculation
      into the cauda. The present findings provide the first morphological data on a
      multisynaptic circuit of neurons innervating the epididymis and presumably
      involved in the control of epididymal functions. reserved.

PMID- 11570698
TI  - The consilience of autonomic neuroscience: can we all work together?

PMID- 11570699
TI  - Responsiveness of intrinsic cardiac neurons to left atrial and hypothalamic
      cardioactive peptides.
AB  - This study was designed to investigate whether cardioactive peptides derived from
      left atrial tissue or the hypothalamus modulate neurons within the intrinsic
      cardiac nervous system. Peptides derived from left atrial or left auricular
      tissues with known coronary artery dilator properties were administered (0.1 ml;
      100 microM dose) individually over 10-s periods into the arterial blood supply of
      ventral ventricular neurons in 11 anesthetized pigs (19-28 kg). Similarly, three
      hypothalamic protein-hormonal complexes that express coronary artery vasodilator
      properties, protein-hormone complexes C, G and K, were studied. Each peptide
      modified the activity generated by some of the neurons identified in a locus of
      the ventral ventricular ganglionated plexus of each animal. The hypothalamic
      peptides elicited primarily excitatory responses, whereas the atrial ones induced
      more suppressor than excitatory responses. Cardiovascular indices remained
      unchanged overall, indicating that observed neuronal effects were not secondary
      to cardiodynamic alterations. These data indicate that intrinsic cardiac neurons
      are sensitive to left atrial and hypothalamic peptides that exhibit coronary
      artery dilator properties.

PMID- 11570700
TI  - Development of obesity and neurochemical backing in aurothioglucose-treated mice.
AB  - To clarify the neurochemical backing of aurothioglucose (ATG)-induced obesity in
      mice, we investigated lesion sites, hypothalamic neurotransmitters and c-Fos-like
      immunoreactivity (Fos-IR). At day 2 after ATG, tissue loss or cells death was
      observed in several parts of the ventral area of the ventromedial hypothalamic
      nucleus (VMH), and the dorsal area of arcuate nucleus and in the nucleus of the
      solitary tract (NTS). However, the greater part of the VMH was retained. Body
      weight began to increase in week 1. Hypothalamic serotonin (5-HT) and the
      metabolites were increased at day 2. The contents of acetylcholine,
      norepinephrine and dopamine in the hypothalamus showed no significant change. In
      week 1, the area shown tissue loss was compacted and plugged up. In the control
      group, most obvious c-Fos-like immunoreactive region was paraventricular nucleus
      (PVN). At day 2, Fos-IR was observed around destroyed regions in the hypothalamus
      and NTS, but few Fos-IR was found in the other regions including PVN. The Fos-IR
      around destroyed regions diminished after week 1. In week 3, Fos-IR in the PVN
      increased. These results suggest that the development of ATG-induced obesity
      cannot be attributed to solely VMH destruction. The restoration processes of the
      neuronal dysfunction involving PVN seem to play an important role in the
      development of obesity. NTS lesion and 5-HT system might contribute to decrease
      in food intake for several days after ATG.

PMID- 11570701
TI  - Effects of vagal and splanchnic section on food intake, weight, serum leptin and
      hypothalamic neuropeptide Y in rat.
AB  - Truncal vagotomy can cause reduced food intake and weight loss in humans and
      laboratory animals. In order to investigate some of the factors that might
      contribute to this effect, we studied changes in ingestive behaviour, whole body
      and organ weights, serum leptin and hypothalamic neuropeptide Y in rats with
      bilateral vagal section, bilateral splanchnic nerve section and combined vagotomy
      plus splanchnectomy. Pyloromyotomy was combined with vagotomy to lessen effects
      of vagotomy on gastric emptying. Animals with vagotomy or vagotomy plus
      splanchnectomy lost weight and decreased their daily food intake relative to
      animals with splanchnectomy alone, rats with bilateral sham exposure of one or
      both nerve, or rats with pyloromyotomy alone. Serum leptin and white fat mass, 4
      weeks after vagotomy, were about 20% of the values in the sham-operated animals
      at this time. No effect for splanchnic nerve section alone was observed.
      Pyloromyotomy caused no reduction in weight or fat mass, but reduced serum
      leptin. Following vagotomy with or without splanchnic nerve section, neuropeptide
      Y was elevated in the arcuate nucleus relative to values for the other four
      groups. Changes in neuropeptide Y were inversely correlated with levels of serum
      leptin. It is concluded that the effect of vagotomy could be due to the loss of a
      feeding signal carried by vagal afferent neurons, or to changed humoral signals,
      for example, increased production of a satiety hormone. However, it cannot be
      attributed to signals that reduce feeding (for example, gastric distension)
      reaching the central nervous system via the splanchnic nerves. The changes were
      sufficient to cause weight loss even though serum leptin was decreased, a change
      that would be expected to increase food intake.

PMID- 11570702
TI  - A reduction in interstitial cells of Cajal in horses with equine dysautonomia
      (grass sickness).
AB  - Equine dysautonomia (grass sickness) is a common, frequently fatal disease of
      horses characterised by dysfunction of the gastrointestinal tract. Interstitial
      cells of Cajal are the c-Kit-immunoreactive cells responsible for the generation
      of pacemaker activity in gastrointestinal smooth muscle. Impairment of this
      pacemaker action has been implicated in several motility disorders in humans and
      laboratory mammals. The aim of this study was to test the hypothesis that changes
      in interstitial cells of Cajal may be involved in the pathophysiology of the
      intestinal dysfunction observed in equine grass sickness. Interstitial cells of
      Cajal were identified using immunohistochemical labelling with an anti-c-Kit
      antibody and their density was assessed using a semi-quantitative grading system.
      Segments of ileum were examined from 24 horses free from gastrointestinal disease
      and compared to tissues from 28 horses with grass sickness. Segments of the
      pelvic flexure region of the large colon were examined from 13 horses free from
      gastrointestinal disease and compared to tissues from 10 horses with grass
      sickness. In horses with grass sickness, interstitial cells of Cajal were
      significantly decreased in both the myenteric plexus and circular muscle regions
      of both ileum and pelvic flexure compared to normal animals. Therefore, it is
      possible that the decline in interstitial cells of Cajal may be an important
      factor in the development of intestinal dysmotility observed in grass sickness.

PMID- 11570703
TI  - Stimulation of 5-HT2 receptors in the nucleus tractus solitarius enhances NMDA
      receptor-mediated reflex-evoked bradycardiac responses in the rat.
AB  - The modulation by 5-HT2 receptors in the nucleus tractus solitarius of the reflex
      bradycardia evoked by stimulation of peripheral baroreceptors and cardiopulmonary
      chemoreceptors, and their possible functional interactions with local NMDA
      receptors, were investigated in pentobarbital- and urethane-anaesthetized rats,
      respectively. Microinjection of the 5-HT2 receptor agonist, 2,5-dimethoxy-4
      iodoamphetamine (0.1-0.5 pmol), into the nucleus tractus solitarius elicited a
      dose-dependent hypotension and bradycardia. Bilateral microinjections at the same
      site of a subthreshold dose of 2,5-dimethoxy-4-iodoamphetamine (0.05 pmol)
      significantly enhanced the aforementioned reflex-evoked bradycardiac responses.
      In contrast, local bilateral microinjections of the NMDA receptor antagonist, 2
      amino-5-phosphonopentanoic acid (500 and 1000 pmol), reduced, in a dose-dependent
      manner, both reflex-evoked responses. The facilitatory effect of 2,5-dimethoxy-4
      iodoamphetamine upon these reflex-evoked bradycardiac responses was prevented by
      prior local microinjection of low doses of either the selective 5-HT2 receptor
      antagonist, ketanserin (10 pmol), or 2-amino-5-phosphonopentanoic acid (100
      pmol), which, on their own, did not affect the reflex-associated bradycardia.
      These data suggest that 5-HT2 receptors within the nucleus tractus solitarius
      participate in a facilitatory modulation of the reflex control of heart rate,
      probably through functional interactions with local NMDA receptors.

PMID- 11570704
TI  - Smooth muscle does not have a common P2x receptor phenotype: expression, ontogeny
      and function of P2x1 receptors in mouse ileum, bladder and reproductive systems.
AB  - The distribution, ontogeny and role of P2x1 receptors were examined in the smooth
      muscle of the mouse intestine, bladder, and male and female reproductive tracts
      using P2x1 receptor subtype selective antibodies and contraction studies. P2x1
      receptor immunoreactivity showed a heterogeneous distribution in smooth muscle
      with high levels expressed in adult vas deferens, bladder, arteries and male
      reproductive organs. In contrast, P2x1, receptors were below the level of
      detection in the smooth muscle of the ileum and female reproductive tract. P2x1
      receptor immunoreactivity was detected at adult levels from birth in the bladder.
      However, in the vas deferens, immunoreactivity was only detected from 10 days
      after birth and reached adult levels by approximately 1 month old. A similar
      pattern of expression was seen in the vesicular seminalis, epididymis, gland of
      the vas deferens and coagulating gland. Sensitivity to the P2x1 receptor agonist
      alpha,beta-methylene ATP (alpha,beta-meATP) and P2x1 receptor-deficient mice were
      used in functional studies to determine the role of P2x1 receptors in the control
      of smooth muscle. alpha,beta-meATP (100 microM) failed to evoke contractions of
      the epididymis, or seminal vesicle and P2x1 receptors did not contribute to the
      control of uterine smooth muscle. In the ileum, alpha,beta-meATP (100 microM)
      evoked a transient relaxation followed by a contraction. These responses were
      abolished by the P2 receptor antagonist iso-pyridoxalphosphate-6-azophenyl-2'-5'
      disulphonate (iso-PPADS) (30 microM). Relaxant responses were abolished by the
      adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (1
      microM). Contractile responses were reduced by > 80% in the ileum from P2x1
      receptor-deficient mice. alpha,beta-meATP-evoked contractions were reduced by
      approximately 35% by TTX (1 microM) and were unaffected by atropine (10 microM).
      These studies indicate that P2x1 receptors are not expressed throughout all
      smooth muscles and that their expression is developmentally regulated. In
      addition, they provide evidence to suggest that P2x1 receptors are present on pre
      synaptic nerve terminals in the enteric nervous system.

PMID- 11570705
TI  - Enhanced colonic peristalsis by impairment of nitrergic enteric neurons in
      spontaneously diabetic rats.
AB  - Changes in enteric neurons containing various neurotransmitters in the colon have
      been described in diabetic rats; however, how these changes are related to
      colonic motility disorders remains unclear. Nitric oxide (NO) is known to be an
      important inhibitory neurotransmitter in the enteric nervous system. In the
      present study, we investigated the peristaltic reflex using our modified
      Trendelenburg's method to evaluate the differences in enteric nitrergic neurons
      of the distal colon between spontaneously diabetic rats and their sibling control
      rats. We measured maximum intraluminal pressure, threshold pressure and
      propagation distance of the reflex contraction. These diabetic rats showed a
      greater maximum intraluminal pressure than that in the control rats. NG nitro-L
      arginine methyl ester (L-NAME) significantly increased the maximum pressure in
      the control rats. Although L-arginine did not change the maximum pressure, sodium
      nitroprusside (SNP) significantly decreased it in these diabetic rats.
      Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase reactivities in
      the myenteric plexus were much weaker in the diabetic rats than those in the
      control rats. These results indicate that the colonic peristaltic reflex is
      enhanced by impairment of enteric nitrergic inhibitory neurons in spontaneously
      diabetic rats.

PMID- 11570706
TI  - Comparison of SSR and QSART in early diabetic neuropathy--the value of length
      dependent pattern in QSART.
AB  - We evaluated postganglionic sympathetic function using the sympathetic skin
      response (SSR) and quantitative sudomotor axon reflex test (QSART) on the feet of
      31 patients with early diabetic neuropathy and 20 age-matched normal controls.
      The amplitude of SSR and the sweat volume of QSART were significantly decreased
      in the diabetic patients. We evaluated the sensitivity of the tests in detecting
      autonomic failure. Out of 31 patients, 14 (45%) had abnormal SSR (14 absent; 17
      present), while 16 of 31 patients (52%) had abnormal QSART (1 absent; 5
      absolutely reduced and 10 showed a length-dependent pattern of reduction). More
      important than differences in sensitivity is the specificity of QSART, which
      specifically evaluates the postganglionic axon (instead of polysynaptic pathways
      in SSR) and provides quantitative data on the severity and pattern of autonomic
      deficit. In normal controls under 65 years of age, there was a significant
      correlation between the amplitude of SSR and the sweat volume of QSART. However,
      there was no significant relationship between these in diabetic patients. These
      results suggest that QSART can evaluate early diabetic neuropathy more precisely
      than SSR.

PMID- 11570707
TI  - Questionnaire-based assessment of pelvic organ dysfunction in Parkinson's
      disease.
AB  - Although patients with Parkinson's disease (PD) experience pelvic organ
      dysfunction of the urinary bladder, bowel and genital organs, an accurate
      incidence of the dysfunction and its characteristics have yet to be ascertained.
      We devised a detailed questionnaire on these three pelvic organ functions in PD
      patients and control subjects, in our search for a hallmark that would
      distinguish between the two groups. The PD group comprised 115 patients; 52 men
      and 63 women, age range 35-69 (average 59) years old, average duration of illness
      6 years, median Hoehn and Yahr stage 3. All were taking levodopa with/without
      dopamine agonists. The control group comprised 391 local individuals who were
      undergoing an annual health survey; 271 men and 120 women, age range 30-69
      (average 48) years old. The questionnaire had three parts: bladder (nine
      questions), bowel (four questions), and sexual (three questions for women, five
      for men) function. Each question was scored from 0 (none) to 3 (severe) with an
      additional quality of life (QOL) index scored from 0 (satisfied) to 3 (extremely
      dissatisfied). The completion rate was 100% for bladder and bowel functions,
      whereas for sexual function, it was 95% (control) and 88% (PD) for men and 82%
      (control) and 60% (PD) for women. As compared with the control group, the
      frequency of dysfunction in the PD group was significantly higher for urinary
      urgency (women 42%, men 54%), daytime frequency (28%, 16%), nighttime frequency
      (53%, 63%), urgency incontinence (25%, 28%), retardation (44% of men),
      prolongation/poor stream (men 70%), straining (women 28%); constipation (63%,
      69%), difficulty in expulsion (men 57%), diarrhea (men 21%); decrease in libido
      (84%, 83%), decrease in sexual intercourse (55%, 88%), decrease in orgasm (men
      87%), and in men, decreases in erection (79%) and ejaculation (79%). The QOL
      index for the PD patients was significantly higher for bladder (27%, 28%) and
      bowel (46%, 59%) but not for sexual dysfunction, despite the group's high
      prevalence of sexual dysfunction. In the PD patients, fecal incontinence was
      associated with urinary incontinence. Stress urinary incontinence and a decrease
      in libido were more common in women than in men. Bladder and bowel dysfunction,
      but not sexual dysfunction increased with the Hoehn and Yahr stage. Sexual
      dysfunction, but neither bladder nor bowel dysfunction, increased with age.
      Patients taking levodopa and bromocriptine more frequently had bladder (voiding
      phase) dysfunction than those taking levodopa only. The findings show that
      bladder, bowel and sexual dysfunction are all prominent in patients with PD.
      Amelioration of pelvic organ dysfunction, particularly bowel dysfunction which
      most affects the quality of life, therefore should be a primary target in the
      treatment of patients with PD.

PMID- 11570708
TI  - Decrease of substance P in the parabrachial nucleus of multiple system atrophy.
AB  - In the parabrachial nucleus (PBN), which has been known to play an important
      regulating role for various autonomic functions, many projecting nerve fiber
      terminals containing substance P (SP) from the nucleus of the solitary tract
      (NTS) and other areas are found and effect a modulatory influence on the
      transmission in the PBN. Postmortem brains were obtained from four multiple
      system atrophy (MSA) patients with autonomic failure and four control patients
      without any nervous disease, and an immunohistochemical staining for SP was
      performed on serial 10-microm-thick sections from paraffin-embedded pons
      including the PBN after immersion fixation in 10% formalin. In the PBN of all MSA
      patients, a marked decrease in SP-like immunoreactive (SPLI) nerve fiber
      terminals was revealed compared with the controls. In addition, an obvious
      astrocytosis was found in the PBN by simultaneous histopathological evaluation,
      for the preservation of neurons themselves. Therefore, the projecting SP pathway
      to the PBN may also be primarily involved in the pathophysiological mechanism of
      the autonomic failure of MSA patients.

PMID- 11570709
TI  - Comparison of aortic arch and carotid sinus distensibility in humans--relation to
      baroreflex sensitivity.
AB  - We compared aortic arch (AA) and carotid sinus (CS) distensibility, and
      determined the relationship between baroreflex sensitivity (BRS) and
      distensibility coefficients of AA and CS (DCAA and DCCS, respectively). In 47
      healthy 19-71-year-old subjects, AA and CS end-diastolic diameter (D) and
      pulsatile distension (delta D) was measured with ultrasound and arterial pressure
      by sphygmomanometer and Finapres. DC was calculated as 2delta D/(D x delta P),
      where delta P is the pulse pressure. BRS was determined by the sequence method.
      Data are given as mean +/- S.D.; significance was set at p < 0.05. DCAA and DCCS
      were linearly related across subjects (r = 0.80, p < 0.001). No difference
      between DCAA and DCCS (3.8 +/- 1.4 x 10(-3) and 4.2 + 2.2 x 10(-3) mm Hg(-1),
      respectively) was found for all subjects (paired t-test). However, at ages < 35
      years, DCCS exceeded DCAA, whereas this relation was reversed at ages > 35 years.
      Age accounted for 53% of variability in DCAA and 73% of variability in DCCS. BRS
      was related to DC (linear regression), with the BRS-DCAA relation being steeper
      and closer (r = 0.73, p < 0.001) than the BRS-DCCS relation (r = 0.54, p < 0.05).
      It is suggested that aortic baroreceptors may have a dominant role in heart rate
      control.

PMID- 11570710
TI  - Founding friends: families and institution building in early 19th century
      Philadelphia.
AB  - BACKGROUND: Nurses have always had an interest in the relationships among
      families, clinicians, and healthcare institutions. This case study of the Friends
      Asylum for the Insane in early 19th century Philadelphia examines the historical
      roots of these relationships. METHODS: Data sources are archival documents about
      the male founders of the Friends Asylum, its constituent families, and the
      committees responsible for the creation and the maintenance of the institution.
      RESULTS: Families seeking a temporary respite from day-to-day turmoil created The
      Friends Asylum in Philadelphia. The Friends Asylum allowed them to continue to
      explore the processes that ultimately gained them an enduring identity as members
      of the newly emerging middle-class. DISCUSSION: These data suggest that the
      Asylum served individuals limited in their capacity for the self-control needed
      for a new kind of middle-class identity and those families vulnerable to the
      demands made by the roots of this new identity. For individuals, it provided a
      place that replicated the intimate domestic ideal. And for families, it allowed
      the sharing of care-taking responsibilities with kin who wanted the insane out of
      the home, but not out of the family. CONCLUSION: In the early 19th century,
      families presented clinicians not just with dilemmas, but with solutions that
      carried substantial cultural weight. This study suggests that theoretical
      innovations in healthcare might draw from the transformations in normative rules
      about domestic, work, and social roles. It suggests that nurses remain aware of
      the possibility that it may not be nurses who empower patients; it may be
      patients who empower nurses.

PMID- 11570711
TI  - Patient decision-making behavior: an emerging paradigm for nursing science.
AB  - BACKGROUND: As healthcare technology and medical therapies proliferate,
      healthcare providers have more options to offer and patients have more options
      from which to choose. Active patient participation in healthcare decision making
      is a relatively new phenomenon that has been born of sociocultural, ethical, and
      legal influences. Patients, however, often find healthcare decisions bewildering,
      stressful, and anxiety-provoking. OBJECTIVES: The purpose of this review is to
      provide a framework for those interested in pursuing patient decision-making
      investigations and suggest ways in which current knowledge can be extended to
      develop a scientific platform upon which to build decision support interventions.
      METHOD: Literature review. DISCUSSION: This review (a) provides a context for
      understanding patient decision making; (b) explicates the state of the science of
      patient decision making; (c) identifies significant theoretical, methodological,
      and measurement issues; and, (d) identifies gaps in patient decision-making
      knowledge and propose areas for further investigation.

PMID- 11570712
TI  - Predictors of postpartum depression: an update.
AB  - BACKGROUND: Approximately 13% of women experience postpartum depression. Early
      recognition is one of the most difficult challenges with this mood disorder
      because of how covertly it is suffered. OBJECTIVES: The purpose of this meta
      analysis was to update the findings of an earlier meta-analysis of postpartum
      depression predictors that had synthesized the results of studies conducted
      mostly in the 1980s. METHOD: A meta-analysis of 84 studies published in the
      decade of the 1990s was conducted to determine the magnitude of the relationships
      between postpartum depression and various risk factors. Using the software system
      Advanced Basic Meta-Analysis, effect sizes were calculated three ways:
      unweighted, weighted by sample size, and weighted by quality index score.
      RESULTS: Thirteen significant predictors of postpartum depression were revealed.
      Ten of the 13 risk factors had moderate effect sizes while three predictors had
      small effect sizes. The mean effect size indicator ranges for each risk factor
      were as follows: prenatal depression (.44 to .46), self esteem (.45 to. 47),
      childcare stress (.45 to .46), prenatal anxiety (.41 to .45), life stress (.38 to
      .40), social support (.36 to .41), marital relationship (.38 to .39), history of
      previous depression (.38 to .39), infant temperament (.33 to .34), maternity
      blues (.25 to .31), marital status (.21 to .35), socioeconomic status (.19 to
      .22), and unplanned/unwanted pregnancy (.14 to .17). CONCLUSIONS: Results
      confirmed findings of an earlier meta-analysis and in addition revealed four new
      predictors of postpartum depression: self-esteem, marital status, socioeconomic
      status, and unplanned/unwanted pregnancy.

PMID- 11570713
TI  - Changes in Meniere's disease responses as a function of the menstrual cycle.
AB  - BACKGROUND: Meniere's disease is a complex, progressive disorder of the inner ear
      evidenced by characteristic responses including vertigo, hearing loss, and
      tinnitus. Though considered equally common across sexes, several recent studies
      describe women's increasing reports of symptom exacerbation during the
      perimenstruum. Empirical evidence proving this relationship is limited with no
      study exploring women's symptom reports using appropriate methodological
      procedures for menstrual cycle research. OBJECTIVES: To establish the
      relationship between menstrual cycle phases and Meniere's disease responses.
      Specific aims included comparison of Meniere's disease responses between
      menstruant women and men (control group) and examination of women's Meniere's
      disease responses and their relationship to their diverse menstrual symptom
      patterns. METHODS: Using a longitudinal, descriptive design, 12 men and 13 women
      were recruited via Internet and participated in daily data collection procedures
      over three study phases. RESULTS: Results showed that Meniere's disease responses
      were similar for men and women participants. Women with premenstrual
      magnification patterns did not vary with cycle phases. However, vertigo (P < .05)
      did decrease significantly postmenses for women with premenstrual syndrome
      patterns. CONCLUSIONS: Results from this study provide evidence that a unique
      relationship does exist between the menstrual cycle and Meniere's disease
      responses for some women. Knowledge gained from this study is beneficial in
      identifying the importance of appropriate clinical assessment methods of
      menstruant women with Meniere's disease. Recommendations include further research
      with larger samples and testing of different symptom management strategies for
      women of different perimenstrual symptom patterns.

PMID- 11570714
TI  - Model testing for reliability and validity of the Outcome Expectations for
      Exercise Scale.
AB  - BACKGROUND: Development of a reliable and valid measure of outcome expectations
      for exercise appropriate for older adults will help establish the relationship
      between outcome expectations and exercise. Once established, this measure can be
      used to facilitate the development of interventions to strengthen outcome
      expectations and improve adherence to regular exercise in older adults.
      OBJECTIVES: Building on initial psychometrics of the Outcome Expectation for
      Exercise (OEE) Scale, the purpose of the current study was to use structural
      equation modeling to provide additional support for the reliability and validity
      of this measure. METHODS: The OEE scale is a 9-item measure specifically focusing
      on the perceived consequences of exercise for older adults. The OEE scale was
      given to 191 residents in a continuing care retirement community. The mean age of
      the participants was 85 +/- 6.1 and the majority were female (76%), White (99%),
      and unmarried (76%). Using structural equation modeling, reliability was based on
      R2 values, and validity was based on a confirmatory factor analysis and path
      coefficients. RESULTS: There was continued evidence for reliability of the OEE
      based on R2 values ranging from .42 to .77, and validity with path coefficients
      ranging from .69 to .87, and evidence of model fit (X2 of 69, df = 27, p < .05,
      NFI = .98, RMSEA = .07). CONCLUSION: The evidence of reliability and validity of
      this measure has important implications for clinical work and research. The OEE
      scale can be used to identify older adults who have low outcome expectations for
      exercise, and interventions can then be implemented to strengthen these
      expectations and thereby improve exercise behavior.

PMID- 11570715
TI  - An adaptation of Brislin's translation model for cross-cultural research.
AB  - BACKGROUND: The number of nurse scientists pursuing cross-cultural research using
      quantitative designs is increasing. Preparation of instruments that are
      conceptually and functionally appropriate in the language of the participants is
      a complex process that needs examination. OBJECTIVES: Brislin's classic model for
      translation and validation of instruments for cross-cultural research is
      critiqued. Adaptations and extensions of that model are recommended. METHODS:
      Brislin's model guided tool preparation in a cross-cultural investigation. The
      process is described and lessons learned are outlined and discussed. CONCLUSIONS:
      Steps toward a more efficient and valid approach to the preparation of
      instruments are suggested.

PMID- 11570716
TI  - Race and ethnicity as variables in Nursing Research, 1952-2000.
AB  - BACKGROUND: Although the use of race and ethnicity as variables in research has
      increased over the past five decades, there is confusion regarding the meaning of
      the terms, as well as how the words are defined and determined in scientific
      inquiry. OBJECTIVE: To review the use of race and ethnicity as variables in
      nursing research literature. METHODS: Original research articles published in
      Nursing Research in the years, 1952, 1955, and every 5 years thereafter through
      2000 were reviewed. Those articles describing human characteristics (N = 337)
      were analyzed for content concerning: (a) frequency of racial and ethnic terms,
      (b) words used for racial and ethnic categories, (c) detinitions of racial and
      ethnic terms, and (d) how a study participant's race or ethnicity was determined.
      RESULTS: Racial and ethnic variables were mentioned in 167 of the 337 reviewed
      articles. Eighty-one terms and word phrases were used for these variables. In
      only five articles were the variables defined. Race and ethnic labels were often
      intermixed and the majority of studies provided no information about how
      categorization of the participant's race or ethnicity was made. In addition,
      there was relatively little growth in the number of studies that had
      racial/ethnic groups, other than Whites, as the majority of the sample.
      CONCLUSION: Racial and ethnic variables provide nurse researchers with many
      challenges. Although race and ethnicity were widely used in Nursing Research
      articles, the categories were not defined in the majority of papers, and methods
      used to determine a participant's race or ethnicity were unclear. In order to
      construct a common and consistent understanding of racial and ethnic categories,
      nurse researchers should be explicit regarding the rationale related to their use
      of the categories and the assumptions underlying particular racial and ethnic
      categorizations.

PMID- 11570717
TI  - "Definite lines of influence": Catholic sisters and nurse training schools, 1890
      1920.
AB  - BACKGROUND: Standard histories of the nurse training school movement have focused
      on national leaders and organizations and have generally not included Catholic
      sisters, even though nuns had established approximately 220 nursing schools by
      1915. OBJECTIVES: This study asks how Catholic sisters used their distinct
      understanding of nursing to shape their nursing schools and the nurse training
      movement in the United States between 1890 and 1920. METHOD: Historical
      methodology draws upon primary sources in archives of three women's religious
      congregations, the Catholic Health Association, and the University of Notre Dame.
      These include nuns' constitutions and letters, hospital chronicles, journals,
      minutes of meetings, training school records, annual reports, yearbooks, census
      records, and educational reports. Secondary sources include nursing, hospital,
      religious, and labor histories. RESULTS: Catholic sisters adapted their nursing
      to bring it into line with modern society by establishing nurse training schools
      for both religious and secular women. This legitimized their nursing practice and
      enhanced their influence with students, physicians, and hospital groups. As nuns
      admitted laywomen into their schools and worked toward accepted standards of
      professionalization, they stamped their distinct understanding of nursing onto
      secular society. DISCUSSION: The development of professionalized nursing drew
      Catholic sisters' schools toward common goals with non-Catholic programs. On the
      other hand, the sisters' historical construction of nursing in the 19th century,
      their unique relationship with physicians, and the obstacles they faced later,
      such as the Roman Catholic clergy's attempt to control evaluation processes,
      indicate a distinct approach to Catholic nursing. Questions remain as to whether
      nuns could hold onto their authority later in the 20th century.

PMID- 11570718
TI  - Oral history of Florence Downs; the early years.
AB  - BACKGROUND: Florence Downs is a well-recognized nursing leader, educator, editor,
      and scholar who helped shape nursing as an intellectual discipline, and wrote
      extensively about the importance of links between research and practice.
      OBJECTIVES: Through the use of oral history data garnered over 15 hours of
      interviews, we constructed a narrative that describes some of Downs' formative
      experiences. METHODS: Oral history is used to place the "stories" of an
      individual into a social and cultural context, in this case, the development of
      the profession of nursing. RESULTS: From the interviews, several strands emerged
      that defined Downs' extended career, including the importance of developing a
      community of scholars both in and outside of nursing, the dangers of
      parochialism, and the necessity of a perspective on life that melded a keen sense
      of humor. Factors that affected Downs' style and choice, especially her mother,
      and her educational experiences, were revealed. DISCUSSION: From the interviews
      we gained a sense of how Downs constructed her conceptual universe of nursing, as
      well as the language and political effectiveness to overcome barriers confronting
      the intellectual growth of nursing mounted by other nursing leaders as well as
      traditional academic disciplines.

PMID- 11570719
TI  - Could capillary zone electrophoresis of tryptic peptides be used for the
      characterization of hemoglobin variants?
AB  - The present article describes a simple and rapid new peptide mapping procedure
      that could be used to assist identification of rare hemoglobin variants in
      clinical laboratories. Four hemoglobin variants were taken as example, namely Hb
      D-Ouled Rabah, Hb Marseille, Hb G-Philadelphia, and Hb Ube-2, and isolated by
      electrophoresis at alkaline pH. The globin chains were aminoethylated and, after
      tryptic digestion, the peptides were separated by a capillary zone
      electrophoresis method. Highly reproducible migration times of the peptides were
      obtained with intra-assay and inter-assay coefficients of variation of less than
      1 and 2%, respectively.

PMID- 11570720
TI  - The thalassemia syndromes: molecular characterization in the Spanish population.
AB  - This work compiles the results of our research on alpha- and beta-thalassemias,
      and includes a literature review of the molecular genetics of alpha- and beta
      thalassemias in Spain. We studied 1,564 subjects with thalassemia (294 with beta
      thalassemia and 1,264 with alpha-thalassemia) by molecular biology techniques. In
      relation to beta-thalassemia, a total of 15 different mutations were
      characterized in a study of 308 chromosomes belonging to 294 unrelated subjects.
      Eleven were homozygotes (22 alleles), three compound heterozygotes (6 alleles),
      and the remaining 280 were heterozygotes (280 alleles). A total of 86.6% of the
      alleles identified can be grouped into five different mutations [IVS-I-1 (G-->A),
      IVS-I-6 (T-->C), IVS-I-110 (G-->A), codon 39 (C-->T), codons 8/9 (+G)]. In 14
      subjects (4.5%), all heterozygotes, it was not possible to identify the
      alteration responsible for the beta-thalassemia. For alpha-thalassemia, 911
      subjects showed heterozygous alpha(+)-thalassemia (872 with -3.7 kb; 14 with -4.2
      kb; two with the deletion of 3.5 kb of DNA, and 23 with nondeletional alpha
      thalassemia). Two hundred and thirty-three subjects had homozygous alpha(+)
      thalassemia (223 for -alpha(-3.7)/-alpha(-3.7)); one for -alpha(-4.2)/-alpha(
      4.2); six for -alpha(-3.7)/-alpha(-4.2); one for -alpha(-3.5)/-alpha(-3.7); one
      for alphaalpha(Nco)/alphaalpha(Nco); one for alpha(HPh)/alpha(Hph)). One hundred
      patients presented with heterozygous alpha(0)-thalassemia (18 of whom were
      progenitors of patients with Hb H disease). The alpha(0) determinant was found in
      20 patients with Hb H disease associated with -alpha(-3.7). From the DNA analysis
      were identified the - -(MED), - -(SEA), - -(SPAN) deletions and the - -(MA)
      mutations; in three cases, a break that affects the distal portion of the short
      arm of chromosome 16; one of these was associated with the ATR-16 (alpha-thal
      with mental retardation) syndrome. Triplication of the alpha genes
      (alphaalphaalpha(-3.7)/alphaalpha) was found in 25 subjects, 16 of whom were
      associated with a heterozygous beta-thalassemia. Only one patient was homozygous
      for the triplication of alpha genes (alphaalphaalpha(-3.7)/alphaalphaalpha(-3.7))
      that was associated with a heterozygous beta-thalassemia. In the Mediterranean
      region preventive programs for thalassemia, based on the detection of
      heterozygote carriers and genetic advice, are not sufficient to reduce the
      incidence of newborns with major thalassemia. Prenatal diagnosis of thalassemias
      has given a new dimension to the prevention of these, but in order to implement
      this, a knowledge of the mutations and the incidence of these, is essential. This
      study, therefore, aims to give a general picture of the molecular genetics of
      thalassemia and its geographical distribution in our area.

PMID- 11570721
TI  - The beta-thalassemia mutation spectrum in the Iranian population.
AB  - Beta-thalassemia is the most common hereditary disease in Iran. More than two
      million carriers of beta-thalassemia live in Iran. Since the Iranian population
      is a mixture of different ethnic groups, it is necessary to determine the
      frequency and distribution of mutations in the different parts of the country.
      For this purpose, we divided Iran in to eight different regions according to the
      geographic and ethnic distribution of the population. Over a 10-year period 1,217
      beta-thalassemia chromosomes of 164 affected patients and 889 unrelated carriers
      were studied using the amplification refractory mutation system-polymerase chain
      reaction technique. We detected 81% beta-thalassemia mutations in the studied
      chromosomes. IVS-II-I (G --> A) was the predominant mutation found in our study
      (34%). Its relative frequency in the north was much higher than other regions,
      and it lessened toward the south, where the IVS-I-5 (G --> C) mutation was more
      common. IVS-I-5 (G --> C) (7.55%), codons 8/9 (+ G) (4.76%), and IVS-I-110 (G -->
      A) (4.76%) were the other most common mutations. The results presented here can
      be used as a basis of prenatal diagnosis of beta-thalassemia in different regions
      of Iran.

PMID- 11570722
TI  - Reliability of isoelectrofocusing for the detection of Hb S, Hb C, and HB D in a
      pioneering population-based program of newborn screening in Brazil.
AB  - Out of 128,326 newborns in the first 6-month period of a population-based
      screening program in Minas Gerais, Brazil, a second sample was obtained at the
      age of 6 months from 4,635 carriers of Hbs AS, AC, and AD which were detected by
      isoelectrofocusing. Discordance in results occurred in only 27 cases (0.6%): in
      seven there was a history of hemotransfusion; errors during pipetting or
      transcription of results occurred in seven cases; it was difficult to
      differenciate between Hbs S and D in eight patients; and the causes were not
      elucidated in five patients. The incidence of Hbs FS and FSC for the total
      population was 1:2,800 and 1:3,450, respectively. Isoelectrofocusing is a very
      reliable method for distinguishing AS, AC, or AD carriers from patients
      presenting with [corrected] variant hemoglobin and beta(+)-thalassemia
      combinations, and may be widely used in massive newborn screening programs.

PMID- 11570723
TI  - Molecular analysis of beta-thalassemia in South Vietnam.
AB  - The high prevalence of beta-thalassemia in Southeast Asia is a major public
      health problem. Development of genetic counseling and prenatal diagnosis programs
      is a priority. To provide the groundwork for such programs in South Vietnam, we
      determined the spectrum of beta-thalassemia mutations in 35 severely affected
      patients and their relatives. We identified six different beta-thalassemia
      alleles (five beta(0) and one beta(+) mutations), in addition to the common
      mutation at codon 26 (GAG --> AAG) responsible for Hb E. These data provide
      insights into the distribution of beta-thalassemia alleles in the Vietnamese
      population.

PMID- 11570724
TI  - A novel splice acceptor site mutation of the alpha2-globin gene causing alpha
      thalassemia.
AB  - A novel nondeletional alpha-thalassemia mutation that affects RNA processing,
      changing the alpha2 IVS-II-142 splice acceptor consensus sequence from AG to AA,
      has been detected in an Argentinian patient with Hb H disease and her daughter.

PMID- 11570725
TI  - Hb D-Agri [beta9(A6)Ser --> Tyr;beta121(GH4)Glu --> Gln]: a new Indian hemoglobin
      variant with two amino acid substitutions in the same beta chain.

PMID- 11570726
TI  - Hb Douala [alpha3(A1)Ser --> Phe]: a new alpha1 gene mutation in a Cameroonian
      woman heterozygous for Hb S and a 3.7 kb deletional alpha-thalassemia.

PMID- 11570727
TI  - Hb 't Lange Land [beta136(H14)Gly --> Arg]: a new hemoglobin variant described in
      a Dutch patient of Chinese origin.

PMID- 11570728
TI  - A second case of Hb Renert [beta133(H11)Val --> Ala].

PMID- 11570729
TI  - Hb Tigraye [beta79(EF3)Asp --> His] in a Caucasian family from Sardinia.

PMID- 11570730
TI  - Compound heterozygosity for Hb S and HB C coexisting with AIDS: a cautionary
      tale.

PMID- 11570731
TI  - Assessment of short-term physical loading of the back: is serum keratin sulfate
      an appropriate biomarker?
AB  - STUDY DESIGN: A prospective experimental study. OBJECTIVES: To investigate the
      potential of serum keratan sulfate (KS) as an indicator of biochemical changes in
      intervertebral discs induced by physical loading of the back. BACKGROUND: By
      providing objective information on exposure and effects at the tissue level,
      biomarkers may enable us to improve our understanding of the intermediate steps
      between exposure to physical loading and the occurrence of back disorders. Serum
      KS has been proposed as a potential biomarker of the molecular changes in
      intervertebral discs that occur because of physical loading and are a potential
      cause of back disorders. METHODS AND MEASURES: Thirty-two nonimpaired men
      volunteers with a mean age of 22.5+/-2.3 years participated in the experimental
      condition, a manual lifting task, as well as in the control condition, lying on
      the back. Serum KS levels were measured immediately before and after both
      conditions, as well as 24 hours and 1 week later. RESULTS: No significant changes
      in serum KS levels were found after exposure to physical loading (mean SD serum
      KS before, 287.4+/-83.9 ng/mL; immediately after, 279.5+/-65.5 ng/mL; 24 hours
      after, 266.6+/-71.9 ng/mL; and 1 week after, 268.9+/-79.3 ng/mL), and no
      significant changes were found after lying on the back for 8 hours (mean+/-SD
      serum KS before, 273.0+/-94.3 ng/mL; immediately after, 261.6+/-68.9 ng/mL; 24
      hours after, 277.3+/-68.9 ng/mL; and 1 week after, 274.5+/-68.5 ng/mL).
      CONCLUSIONS: These results indicate that the serum KS level is not suitable as a
      biomarker of the effects of short-term physical loading of the back induced by a
      manual lifting task.

PMID- 11570732
TI  - Giving way event during a combined stepping and crossover cutting task in an
      individual with anterior cruciate ligament deficiency.
AB  - STUDY DESIGN: Case study. OBJECTIVE: To compare knee kinematics and moments of
      nongiving way trials to a giving way trial during a combined stepping and
      crossover cutting activity. BACKGROUND: The knee kinematics and moments
      associated with giving way episodes suggest motor control strategies that lead to
      instability and recovery of stability during movement. METHODS AND MEASURES: A 27
      year-old woman with anterior cruciate ligament deficiency reported giving way
      while performing a combined stepping and crossover cutting activity. A motion
      analysis system recorded motion of the pelvis, femur, tibia, and foot using 3
      infrared emitting diodes placed on each segment at 60 Hz. Force plate recordings
      at 300 Hz were combined with limb inertial properties and position data to
      estimate net knee joint moments. The stance time, foot progression angle, and
      cutting angle were also included to evaluate performance between trials. RESULTS:
      Knee internal rotation during the giving way trial increased 3.2 degrees at 54%
      of stance relative to the nongiving way trials. Knee flexion during the giving
      way trial increased to 33.1 degrees at 66% of stance, and the knee moment
      switched from a nominal flexor moment to a knee extensor moment at 64% of stance.
      The knee abductor moment and external rotation moment during the giving way trial
      deviated in early stance. CONCLUSIONS: The observed response to the giving way
      event suggests that increasing knee flexion may enhance knee stability for this
      subject. The transverse and frontal plane moments appear important in
      contributing to the giving way event. Further research that assists clinicians in
      understanding how interventions can impact control of movements in these planes
      is necessary.

PMID- 11570733
TI  - Application and interpretation of simple odds ratios in physical therapy-related
      research.
AB  - Over the past several decades, physical therapists have demonstrated an
      increasing responsiveness to the profession's obligation to generate objective
      evidence for examination and intervention strategies employed in physical therapy
      practice. This trend is evident, not only in the increasing number of journals
      that are publishing physical therapy research, but in the growing sophistication
      of research design and analytic options used by investigators. At the same time,
      physical therapists are held increasingly accountable for adopting an evidence
      based approach to practice. The result for many of us is a growing concern about
      our ability to interpret study findings. The ability to independently weigh the
      importance to our own practice of evidence reported in a study requires that we
      understand the strengths and potential weaknesses of the sample, design, and
      analyses being used. The odds ratio (OR) is one of the analytic measures that has
      only recently appeared in the physical therapy literature. Because the OR may be
      unfamiliar to physical therapists, the goal of this paper is to provide a
      description of the simple OR and a discussion of its uses, interpretation, and
      potential limitations.

PMID- 11570734
TI  - Factors contributing to the development of medial tibial stress syndrome in high
      school runners.
AB  - STUDY DESIGN: Predictive correlational study. OBJECTIVES: To identify the
      incidence of medial tibial stress syndrome (MTSS) in a group of high school cross
      country runners and to determine if a relationship exists between lower extremity
      structural measures and the incidence of MTSS. BACKGROUND: Medial tibial stress
      syndrome is an overuse injury that occurs in long-distance runners. Literature
      exists that implicates structural deformity as a contributor to MTSS, but no
      studies have developed a predictive model. METHODS AND MEASURES: We measured 125
      high school cross-country runners for tibiofibular varum, resting calcaneal
      position during stance, and gastrocnemius length. Runners developing MTSS over an
      8-week period were placed in the injured group (2 men, 13 women; age 15.3 years
      1.0), and 21 randomly selected uninjured runners were placed in the uninjured
      group (13 men, 8 women; age 15.7 years +/-1.5). Navicular drop was measured for
      runners in both groups. Reliability of measures was determined using an
      intraclass correlation coefficient (ICC 3,1). Paired t tests were used to compare
      the injury and noninjury groups. A logistic regression analysis was used to
      establish if the descriptive data could accurately predict the development of
      MTSS. RESULTS: Paired t tests showed a significant difference in navicular drop
      test measures between the injured (6.8 mm 3.7) and noninjured (3.6 mm 3.3)
      groups. Logistic regression analysis revealed navicular drop test measurements
      and sex correctly identified athletes who developed MTSS with 76% accuracy.
      CONCLUSION: Our study supported the hypothesis that a pronatory foot type is
      related to MTSS. The combination of sex and navicular drop test measures provides
      an accurate prediction for the development of MTSS. Clinical measures that
      identify biomechanical risk factors for MTSS may allow prevention or early
      intervention.

PMID- 11570735
TI  - Augmented feedback reduces jump landing forces.
AB  - STUDY DESIGN: Randomized, experimental design using a 1-way ANCOVA to determine
      the influence of various forms of feedback on jump landing forces. OBJECTIVE: To
      investigate the effects of augmented feedback versus sensory feedback on the
      reduction of jump landing forces. BACKGROUND: Several investigators have reported
      an increased risk of lower extremity injury associated with landing from a jump.
      METHODS AND MEASURES: Nonimpaired college students (N=63) were randomly assigned
      to 1 of 4 feedback groups. Subjects were instructed to perform maximal vertical
      jumps onto a force plate for 3 testing sessions (baseline, 2-minute post-test,
      and 1-week post-test). Three feedback groups (augmented, sensory, and control I)
      were tested during all 3 testing sessions, while a fourth feedback group (control
      II) was evaluated at only 2 sessions (baseline and 1-week post-test). Subjects in
      the augmented feedback condition were provided information via video and verbal
      analysis of how to land softer. Subjects in the sensory feedback condition were
      asked to use the experience of their baseline jumps to document how they could
      land softer. Subjects in each of the control groups were not provided any
      extraneous feedback. Peak vertical ground reaction force data were collected for
      analysis. RESULTS: The subjects in the augmented feedback group significantly
      reduced their peak vertical ground reaction force in both post-test conditions (2
      minute post-test reduction, 0.85+/-0.62; 1-week post-test reduction, 0.74+/-0.58)
      as compared to the sensory, control I, and control II feedback groups.
      CONCLUSIONS: High impact landing forces may be reduced by the implementation of
      augmented feedback information instructing individuals about how to land
      properly. The reduction of jump landing forces with the use of augmented feedback
      may prove beneficial in the creation of instructional landing programs.

PMID- 11570736
TI  - Neural mobilization: the need for more answers.

PMID- 11570737
TI  - Support for neural tissue mobilization.

PMID- 11570738
TI  - More to neurodynamic testing.

PMID- 11570739
TI  - In defense of neural mobilization.

PMID- 11570740
TI  - Negative overgeneralizations about collegiate athletics.

PMID- 11570741
TI  - Collegiate athletics: benefits worth the cost.

PMID- 11570742
TI  - "Rape" poor choice of words.

PMID- 11570743
TI  - Athletics and academics can coexist.

PMID- 11570744
TI  - Positive stories on collegiate athletics.

PMID- 11570745
TI  - Questions about traction.

PMID- 11570746
TI  - Doubly rotated contoured quartz resonators.
AB  - Doubly rotated contoured quartz resonators are used in the design of temperature
      compensated stable clocks and dual-mode sensors for simultaneous measurements of
      pressure and temperature. The design of these devices is facilitated by models
      that can predict frequency spectra associated with the three thickness modes and
      temperature and stress-induced frequency changes as a function of crystalline
      orientation. The Stevens-Tiersten technique for the analysis of the C-mode of a
      doubly rotated contoured quartz resonator is extended to include the other two
      thickness modes. Computational results for harmonic and anharmonic overtones of
      all three thickness modes of such resonators help in optimizing the radius of
      curvature of the contour and electrode shape for suppression of unwanted modes
      and prevention of activity dips. The temperature and stress-induced changes in
      thickness-mode resonator frequencies are calculated from a perturbation technique
      for small dynamic fields superposed on a static bias. The static bias refers to
      either a temperature or stress-induced static deformation of the resonator plate.
      Phenomenological models are also used for calculating the temperature and stress
      induced changes in resonant frequencies as a function of crystalline orientation.
      Results for the SBTC-cut quartz plate with a spherical convex contour of 260 mm
      indicate that normal trapping occurs for the third (n = 3) and fifth (n = 5)
      harmonic of the A-mode, the fundamental (n = 1) and third (n = 3) harmonic of the
      B-mode, and the fundamental (n = 1) and fifth (n = 5) harmonic of the C-mode.

PMID- 11570747
TI  - Excitation and propagation of shear-horizontal-type surface and bulk acoustic
      waves.
AB  - This paper reviews the basic properties of shear-horizontal (SH)-type surface
      acoustic waves (SAWs) and bulk acoustic waves (BAWs). As one of the simplest
      cases, the structure supporting Bleustein-Gulyaev-Shimizu waves is considered,
      and their excitation and propagation are discussed from various view points.
      First, the formalism based on the complex integral theory is presented, where the
      surface is assumed to be covered with an infinitesimally thin metallic film, and
      it is shown how the excitation and propagation of SH-type waves are affected by
      the surface perturbation. Then, the analysis is extended to a periodic grating
      structure, and the behavior of SH-type SAWs under the grating structure is
      discussed. Finally, the origin of the leaky nature is explained.

PMID- 11570748
TI  - Modeling piezoelectric and piezomagnetic devices and structures via equivalent
      networks.
AB  - A history of equivalent circuit modeling of acoustic structures is presented.
      This is followed by a tutorial development of their use to represent
      piezoelectric (PE) and piezomagnetic (PM) plate transducers and bimorph
      cantilever beams for the purpose of facilitating transition of modern
      micro/nanotechnology creations to practical sensor, actuator, and transducer
      applications. Circuit approximations of various types are derived from the more
      general networks.

PMID- 11570749
TI  - Finite element simulations of thin-film composite BAW resonators.
AB  - A finite element method (FEM) formulation is presented for the numerical solution
      of the electroelastic equations that govern the linear forced vibrations of
      piezoelectric media. A harmonic time dependence is assumed. Both of the
      approaches, that of solving the field problem (harmonic analysis) and that of
      solving the corresponding eigenvalue problem (modal analysis), are described. A
      FEM software package has been created from scratch. Important aspects central to
      the efficient implementation of FEM are explained, such as memory management and
      solving the generalized piezoelectric eigenvalue problem. Algorithms for reducing
      the required computer memory through optimization of the matrix profile, as well
      as Lanczos algorithm for the solution of the eigenvalue problem are linked into
      the software from external numerical libraries. Our FEM software is applied to
      detailed numerical modeling of thin-film bulk acoustic wave (BAW) composite
      resonators. Comparison of results from 2D and full 39 simulations of a resonator
      are presented. In particular, 3D simulations are used to investigate the effect
      of the top electrode shape on the resonator electrical response. The validity of
      the modeling technique is demonstrated by comparing the simulated and measured
      displacement profiles at several frequencies. The results show that useful
      information on the performance of the thin-film resonators can be obtained even
      with relatively coarse meshes and, consequently, moderate computational
      resources.

PMID- 11570750
TI  - Combined FEM and Green's function analysis of periodic SAW structure, application
      to the calculation of reflection and scattering parameters.
AB  - Because of more and more stringent requirements on SAW filter performances, it is
      important to compute, with very good accuracy, the SAW propagation
      characteristics, which include the calculation of reflection and scattering
      parameters. For that reason, the analysis of periodic structures on a semi
      infinite piezoelectric substrate is one of the most important problems being
      investigated by SAW researchers. For infinite periodic grating modeling, we
      developed numerical mixed FEM/BEM (finite element method-boundary element method)
      models using an efficient interpolation basis function that takes into account
      the singularity at both edges of each electrode. In this paper, a review of the
      numerical program that has been developed during the past few years will be
      presented. For an infinite periodic grating, it is convenient to solve the
      propagation problem in the Fourier domain (wave number space and harmonic
      excitation), and important efforts have been spent to properly integrate the so
      called periodic harmonic Green function. Using this numerical model together with
      the general P- matrix formalism, it is possible to compute all of the basic
      parameters with a very good accuracy. These consist of the single strip
      reflectivity, acoustic wave-phase velocity, and position offset between
      reflection and transduction centers. Simulations and comparisons with experiments
      are shown for each model.

PMID- 11570751
TI  - One-dimensional equations for a piezoelectric ring and applications in a
      gyroscope.
AB  - One-dimensional equations for coupled in-plane extensional and flexural
      vibrations of a piezoelectric ring are derived. The equations are used to analyze
      a ring piezoelectric gyroscope. Free and forced vibration solutions are obtained.
      Resonant frequencies and voltage sensitivity as well as their dependence on
      rotation rate and other parameters are examined.

PMID- 11570752
TI  - Sidelobe cancellation technique for achieving high rejection in SAW filters.
AB  - A new technique called sidelobe cancellation technique (SCT) to achieve high
      stopband rejection in SAW filters is described, for varying requirements of shape
      factor and sidelobe levels, by using an eigen function approach. Cosine series
      functions with improved sidelobe levels are employed. Each design is
      characterized by the order of the cosine series and the number of functions used
      to obtain a particular shape factor and rejection. Limited trimming of shape
      factor also can be achieved in each design. The filters described here are
      compared with the Kaiser window filter and are found to be efficient. Measured
      response of a prototype SAW filter using the approach given in this paper is
      plotted, and it is in good agreement with the simulated response.

PMID- 11570753
TI  - Quasi-static analysis of floating-electrode unidirectional SAW transducers.
AB  - The quasi-static theory of SAW transducers is a simplified Green's function
      analysis that has previously been shown to be effective for transducers in which
      short-circuit reflections are negligible. Here, the theory is extended to allow
      for floating electrodes, which occur in floating-electrode unidirectional
      transducers (FEUDTs). An analysis for the coupled-mode (COM) parameters of FEUDTs
      is developed, giving the capacitance, transduction, and reflection parameters and
      the locations of the transduction and reflection centers. For a FEUDT with six
      electrodes per period, algebraic results are obtained in terms of Legendre
      function expressions, giving the COM parameters as functions of metalization
      ratio. These results agree with earlier derivations by other authors, but they
      are obtained much more simply. Numerical results are straightforward to obtain. A
      FEUDT with five electrodes per period is also analyzed, showing that it performs
      similarly to the six-electrode type.

PMID- 11570754
TI  - Modeling a longitudinally coupled dual-mode leaky-SAW resonator filter with
      enhanced upper-sideband suppression.
AB  - Recently, it has been experimentally reported that enhanced upper-sideband
      suppression of a longitudinally coupled (first/third) dual-mode leaky SAW (LSAW)
      resonator filter may be obtained by incorporation of a selectively valued
      capacitor between input and output terminals. In this paper, coupling-of-modes
      (COM) and bandstop-filter modeling is applied to realize this enhanced
      suppression. Tradeoffs are examined between upper and lower side-band suppression
      levels caused by the ensuing capacitive coupling between input and output
      terminals. Good agreement is obtained between this theory and reported
      experimental results for an 800-MHz band cellular filter.

PMID- 11570755
TI  - Analysis of 3-D vibrations of rectangular AT-cut quartz plates with a bi-mesa
      structure.
AB  - A method to analyze 3-D vibrations of rectangular AT-cut quartz bi-mesa-shaped
      plates is developed. The method is based on a classical approach. As in 2-D
      analysis, the half structure of a plate is separated into a thick bi-mesa and a
      thin-side portion, and the displacement field of each region is represented by a
      linear combination of guided waves. In the 3-D analysis, we apply the 2-D finite
      element method (FEM) to obtain the waves guided by two pairs of parallel
      surfaces. The orthogonal property of guided modes is incorporated to
      approximately fulfill the continuity conditions at the interface between the
      thick and thin portions. The stress-free conditions on the plate edges are
      satisfied by employing the method of weighted residuals (MWR). The computational
      advantage of this method is that it can greatly reduce the matrix size compared
      with the 3-D FEM. As a numerical example, the frequency spectra are calculated
      for X-elongated plates of bi-mesa shape, and the strong energy-trapping effect on
      the fundamental thickness-shear (TS) resonance is verified.

PMID- 11570756
TI  - On the existence of surface acoustic waves on piezoelectric substrates.
AB  - The existence of surface waves on anisotropic materials was proven under fairly
      general conditions by Lothe and Barnett in 1976 [1]. But, until now, the status
      of surface waves on piezoelectric materials has remained unresolved. This paper
      presents general existence theorems for surface waves on piezoelectric
      substrates. It is demonstrated that for short circuit boundary conditions a
      surface wave solution must exist under virtually any circumstances. However, for
      a free surface, comparatively stringent existence conditions are required.
      Numerical examples are given for both free and shorted surfaces, and it is
      demonstrated that, in some situations, a surface wave solution may not exist for
      free surface propagation. The existence proofs were developed as a result of
      theoretical work on Green function modeling, which is now the preferred technique
      for rigorous SAW and pseudo-SAW device analysis. The mechanisms of the existence
      proofs and the associated mathematical results give great insight into the
      structure and properties of the Green functions and include many results that are
      directly relevant to device analysis.

PMID- 11570757
TI  - A model-updating procedure to stimulate piezoelectric transducers accurately.
AB  - The use of numerical calculations based on finite element methods (FEM) has
      yielded significant improvements in the simulation and design of piezoelectric
      transducers piezoelectric transducer utilized in acoustic imaging. However, the
      ultimate precision of such models is directly controlled by the accuracy of
      material characterization. The present work is dedicated to the development of a
      model-updating technique adapted to the problem of piezoelectric transducer. The
      updating process is applied using the experimental admittance of a given
      structure for which a finite element analysis is performed. The mathematical
      developments are reported and then applied to update the entries of a FEM of a
      two-layer structure (a PbZrTi-PZT-ridge glued on a backing) for which
      measurements were available. The efficiency of the proposed approach is
      demonstrated, yielding the definition of a new set of constants well adapted to
      predict the structure response accurately. Improvement of the proposed approach,
      consisting of the updating of material coefficients not only on the admittance
      but also on the impedance data, is finally discussed.

PMID- 11570758
TI  - Acoustic wave propagation in continuous functionally graded plates: an extension
      of the Legendre polynomial approach.
AB  - The propagation of guided waves in continuous functionally graded plates is
      studied by using Legendre polynomials. Dispersion curves, and power and field
      profiles are easily obtained. Our computer program is validated by comparing our
      results against other calculations from the literature. Numerical results are
      also given for a graded semiconductor plate. It is felt that the present method
      could be of quite practical interest in waveguiding engineering, non-destructive
      testing of functionally graded materials (FGMs) to identify the best inspection
      strategies, or by means of a numerical inversion algorithm to determine through
      thickness gradients in material parameters.

PMID- 11570759
TI  - Extraction of all coefficients of coupled-mode equations for natural, single
      phase, unidirectional SAW transducers from dispersion characteristics computed by
      hybrid finite element method.
AB  - A numerical method is presented for determining all of the coefficients of
      coupled-mode equations for natural, single-phase, unidirectional SAW transducers
      (NSP-UDTs). Substituting numerical results computed by the hybrid finite element
      method for infinite NSPUDTs with shorted and open electric ports into several
      relations derived from the coupled-mode theory, we can determine all of the
      coefficients. Specifically, the edge frequencies of a stop-band and the static
      capacitances yield the self-coupling coefficients and the amplitudes of mutual
      coupling and transduction coefficients, and the electric potential standing wave
      on the substrate surface, which can be derived from the projection of the
      standing wave distributions of particle displacements and electric potential in
      the whole substrate onto the set of those predicted by the coupled-mode theory,
      yields the phases of mutual-coupling and transduction coefficients. NSPUDTs on ST
      25 degrees X quartz, Y-51.25 degrees Z LiTaO3, and 50 degrees Y-25 degrees X
      La3Ga5SiO14 substrates are investigated. Our results agree well with the earlier
      experimental ones.

PMID- 11570760
TI  - Analysis of thickness modes of contoured doubly rotated, quartz resonators.
AB  - It is the intent of this work to provide a working resource for calculating all
      three mode families of a doubly rotated, contoured quartz resonator. It is shown
      that the theoretical development of Stevens and Tiersten [1] can be used for this
      purpose. Their approach uses a transformation of the mechanical displacement
      vector to the eigenvector triad of the pure thickness solution. The solution
      methodology here reorganizes the transformation matrix Q in their formulation to
      calculate the other two mode families. Calculations compare well with
      experimental results for the three mode families of an SC-cut crystal and an FC
      cut crystal and with published calculations for the SBTC-cut mode family with
      major displacement along the x3 blank axis. The key constants for the SC-cut are
      presented for workers to use in the future. In addition, the equations of motion
      and boundary conditions are derived for the two additional mode families using
      assumptions parallel to those used by Stevens and Tiersten [1]. Calculations with
      these equations are presented for completeness to support the present conclusions
      by showing the equivalence of either simply reorganizing the Q matrix or using
      separate equations for each of the three mode families.

PMID- 11570761
TI  - Impact of SAW device passivation on RF performance.
AB  - Passivation layers consisting of sputtered A12O3 have been deposited onto SAW
      devices for the purpose of reducing the incidence of shorts. A coupling-of-modes
      model was used with one-port resonators, coupled resonator filters (CRF), and
      test structures. The passivation layer stiffens the surface with a velocity
      increase proportional to tau/lambda, where tau is the passivation layer
      thickness. Attenuation is increased slightly, producing a 0.25-dB increase in the
      loss of a one-port resonator at 314 MHz. The effect on reflectivity is minimal
      and of much lesser importance to the designer.

PMID- 11570762
TI  - An extended Butterworth-Van Dyke model for quartz crystal microbalance
      applications in viscoelastic fluid media.
AB  - An extended Butterworth-Van Dyke (EBVD) model with frequency-independent
      parameters for the characterization of a resonant compound formed by a quartz
      crystal in contact with a finite viscoelastic layer contacting a semi-infinite
      viscoelastic medium is extracted by analysis of the lumped element model. The
      formulation of the EBVD model is compared with the complete expression of the
      electrical admittance of the loaded quartz derived from the transmission line
      model (TLM). Relative deviations between them do not exceed 3% around 1%
      bandwidth near resonance. An extended Martin & Granstaff's model and an explicit
      expression for the frequency shift that supposes an extension of Kanazawa's model
      for viscoelastic media are obtained. An analysis of the errors associated with
      the extraction of shear parameters of the coating for different materials prove
      that, to obtain an error less than 5% in the shear parameters determination, the
      viscoelastic contribution, defined as the relative error in the thickness
      computed from the frequency shift by Sauerbrey equation, must be greater than a
      limit that depends on Q, which is defined as the ratio of the shear storage
      modulus (G') to shear loss modulus (G"). In the materials studied, polymers in
      the transition range or in the rubbery state with Q = 1 and 10, the viscoelastic
      contribution must be higher than 15% and 50%, respectively, for a 5% limit error
      in the shear parameters extraction. A criterion for a practical determination of
      the appropriate viscoelastic regimes is indicated.

PMID- 11570763
TI  - A multi-IDT input tunable surface acoustic wave filter.
AB  - Tunable surface acoustic wave (SAW) filters (TSF) have been widely used in the
      wireless telecommunication systems. A prototype of a multi-IDT (interdigital
      transducer) input TSF has been developed. The device consists of 11 IDT
      paralleled in the SAW propagation path. Different SAW filter configurations are
      realized by selecting or combining various IDTs, resulting in the tunability of
      both center frequency and 3 dB bandwidth. The center frequencies of the SAW
      filter range from 126.8 to 199.1 MHz; the 3 dB bandwidths range from 15.2 to 58.9
      MHz. Impedance weighting methods have been applied. The passband ripple has been
      reduced from 6.44 to 1.37 dB after resistance weighting.

PMID- 11570764
TI  - Analysis of SAW properties of epitaxial ZnO films grown on R-Al2O3 substrates.
AB  - ZnO thin films with a high piezoelectric coupling coefficient are widely used for
      high frequency and low loss surface acoustic wave (SAW) devices when the film is
      deposited on top of a high acoustic velocity substrate, such as diamond or
      sapphire. The performance of these devices is critically dependent on the quality
      of the ZnO films as well as of the interface between ZnO and the substrate. In
      this paper, we report the studies on piezoelectric properties of epitaxial (1120)
      ZnO thin films grown on R-plane sapphire substrates using metal organic chemical
      vapor deposition (MOCVD) technique. The c-axis of the ZnO film is in-plane. The
      ZnO/R-Al2O3 interface is atomically sharp. SAW delay lines, aligned parallel to
      the c-axis, were used to characterize the surface wave velocity, coupling
      coefficient, and temperature coefficient of frequency as functions of film
      thickness to wavelength ratio (h/lambda). The acoustic wave properties of the
      material system were calculated using Adler's matrix method, and the devices were
      simulated using the quasi-static approximation based on Green's function
      analysis.

PMID- 11570765
TI  - Finite element simulation and modeling of 2-D arrays for 3-D ultrasonic imaging.
AB  - Issues of modeling and design of 2-D arrays in three dimensions with finite
      element code are discussed. These ultrasonic arrays are used for real time
      dynamic imaging of the heart. Topics include optimization, sensitivity, and
      performance and methods to speed up the run times required for computer
      simulations of large three-dimensional models. Empirical results from 45 x 45 2-D
      arrays are also presented.

PMID- 11570766
TI  - Passband widening of transversely coupled resonator filters using the fundamental
      symmetric and antisymmetric modes.
AB  - This paper describes a method for widening the passband of transversely coupled
      resonator filters (TCF) using only the fundamental symmetric and antisymmetric
      modes. The coupling of modes analysis in the transverse direction is applied to
      the TCF design to investigate the passband width. As a result, it is found that
      the passband width can be increased by making the surface acoustic wave (SAW)
      velocity difference between the interdigital transducer (IDT) region and the
      resonator gap region smaller. It is proposed that a grating structure be applied
      to the common ground bar, instead of the uniform metal, to reduce the SAW
      velocity difference. Using the grating-type common ground bar, filters are
      fabricated on ST-quartz substrate. The passband of a single filter with a center
      frequency of 248 MHz is widened up to 410 kHz without any increase of the
      insertion loss. The effect of the impedance mismatch at the junction of two
      cascaded devices is investigated. It is shown that the filter performance is
      improved by reduction of the small parasitic capacitance existing at the cascade
      point. Experimentally, the capacitance formed between the bus bar of the IDT and
      the bottom surface of the ceramic package is reduced. The insertion loss is
      reduced by 0.6 dB, and 3-dB passband is widened by 8 kHz for a filter with a
      center frequency of 248 MHz. On the basis of these two improvements, cascaded
      TCFs are fabricated. For a filter with a center frequency of 248 MHz, an
      insertion loss of 5.5 dB and a 3-dB passband width of 270 kHz are obtained.

PMID- 11570767
TI  - New capabilities for optimizing SAW gas sensors.
AB  - It is shown how the performances of SAW gas sensors can be optimized based on
      pure acoustic peculiarities of SAW propagation in anisotropic single crystals.
      For a given gas and sensitive membrane, the calibration curve (dependence of the
      response R versus gas concentration n), the sensitivity S (slope of the
      calibration curve: S = dR/dn), the detection limit nth, (cut-off of the curve at
      the threshold Pthr), and the resolution deltan of the sensor (recognition of two
      close concentrations) can be controlled by a proper choice of the substrate
      material and its crystallographic orientation (cut and direction of the SAW
      propagation). An experimental test of this property is performed on SAW devices
      implemented on different substrate materials and crystallographic orientations,
      both uncoated or coated, with a sorbent membrane of polycrystalline Pd or Pd:Ni
      film, upon exposure to humid air as a test analyte.

PMID- 11570768
TI  - Effects of bulk wave radiation on IDT admittance on 42 degrees YX-LiTaO3.
AB  - This paper investigates the effects of bulk acoustic wave (BAW) radiation on the
      admittance of interdigital transducers (IDTs) with significant internal
      reflections of shear horizontal (SH) type leaky surface acoustic waves (SAWs) on
      42 degrees YX-LiTaO3 (42-LT). Theoretical analysis is made by using the discrete
      Green function theory, and synchronous one-port resonators are analyzed. It is
      shown that the BAW radiation significantly affects the IDT characteristics even
      for resonators; under certain circumstances, BAWs launched from an IDT are
      converted into SH-type SAWs by the strong internal reflections, and they interact
      with the BAWs radiated by the IDT. Then, the net amount of the radiated BAW power
      is highly dependent upon the number of IDT finger pairs. For the precise
      simulation of devices based on the SH-type SAWs with strong internal reflections,
      the BAW radiation should carefully be taken into consideration. If the BAW
      radiation is ignored, the radiated power of the SH-type SAWs may seem to be
      negative above the BAW cut-off frequency.

PMID- 11570769
TI  - Theory and design of piezoelectric resonators immune to acceleration: present
      state of the art.
AB  - A typical low noise oscillator uses a crystal resonator as the frequency
      determining element. An understanding of the fundamental nature of acceleration
      sensitivity in crystal oscillators resides primarily in understanding the
      behavior of the crystal resonator. The driving factor behind the acceleration
      induced frequency shift is shown to be deformation of the resonator. The
      deformation drives two effects: an essentially linear change in the frequency
      determining dimensions of the resonator and an essentially nonlinear effect of
      changing the velocity of the propagating wave. In this paper, the fundamental
      nature of acceleration sensitivity is reviewed and clarified, and attendant
      design guidance is developed for piezoelectric resonators. The basic properties
      of acceleration sensitivity and general design guidance are developed through the
      simple examples of "bulk acoustic wave (BAW) in a box" and "surface transverse
      wave (STW) in a box." These examples serve to clarify a number of concepts,
      including the role of mode shape and the basic difference between the BAW and STW
      cases. The design equations clarify the functional dependencies of the
      acceleration sensitivities on the full range of crystal resonator design and
      fabrication parameters.

PMID- 11570770
TI  - A multi-resolution wireless force sensing system based upon a passive SAW device.
AB  - Referring to the technology of SAW wireless identification systems, a multi
      resolution wireless force sensing system, including a passive time-delay SAW
      device and a specific interrogation unit, is introduced in this paper. Using an
      IDT, which connects with an antenna, as the force sensing element is a design to
      transduce the electromagnetic wave into surface acoustic wave and vice versa.
      Several reflectors are designed to get multi-resolution. Sample/hold devices are
      used instead of high-speed A/D converter to construct a low-cost interrogation
      system. Properties of the sensing system are theoretically predicted and
      experimentally verified.

PMID- 11570771
TI  - Optimal cut for leaky SAW on LiTaO3 for high performance resonators and filters.
AB  - The paper describes how the characteristics of leaky surface acoustic wave (LSAW)
      propagation depend on the thickness of Al grating electrodes on rotated Y-X
      LiTaO3. It is shown that the propagation loss arising from leaky nature changes
      parabolically with both the grating electrode thickness and rotation angle and
      becomes zero when electrode thickness and rotation angle are properly determined.
      This means that even when thick grating electrodes are needed in device design,
      zero propagation loss is always realized by properly determining the rotation
      angle. When the grating electrode thickness is 0.07 to 0.1 in wavelength for
      example, LSAWs on 40-42 degrees Y-X LiTaO3 give zero propagation loss without
      deteriorating other characteristics. Ladder-type filters for the 800-MHz range
      were fabricated, which essentially need thick Al grating electrodes of about 0.1
      wavelength thickness. As predicted by theoretical calculation, experimental
      results showed that if the rotation angle is increased to circa 420 from a
      conventional value of 36 degrees, the insertion loss and shape factor are
      markedly improved compared with devices based on 36 degrees Y-X LiTaO3. This is
      essentially a result of the minimized propagation loss.

PMID- 11570772
TI  - A unified formalism using effective surface permittivity to study acoustic waves
      in various anisotropic and piezoelectric multilayers.
AB  - A unified formalism is presented that uses the effective surface permittivity
      (ESP) to study surface acoustic waves (SAW) in layered substrates and guided
      waves in layered plates. Based on known mathematical tools, such as ordinary
      differential equation and transfer matrix, a generalized surface impedance (GSI)
      concept is developed and exploited to investigate the acoustic propagation in
      various anisotropic and piezoelectric layered structures. The ESP function,
      originally defined for the surface of a homogeneous and semi-infinite
      piezoelectric substrate, is extended to both the top surface of and an interface
      in a layered half space, as well as to either surface of a finite-thickness
      plate. General ESP expressions for all mentioned configurations are derived in
      terms of an equivalent GSI matrix. It is shown that, when using the appropriate
      GSI matrices, the same form of the ESP expressions applies no matter whether the
      structure is a homogeneous half space alone or coated with a layered plate or a
      layered plate alone. GSI matrices are explicitly given in terms of the bulk
      partial mode solutions for a substrate and via the transfer matrix for a plate.
      Modified GSI matrices for structures consisting of both a plate and a substrate
      are also specified. Analytical development is fully detailed to suit program
      implementation. To illustrate its versatility, the formalism is also applied to
      two-substrate configurations, allowing one to analyze guided waves in a plate
      sandwiched between and interfacial waves existing along the boundary of two
      different media. Numerical examples are given to illustrate the spectrum features
      that the ESP shows for various structures. Deduced ESP expressions allow one to
      locate directly all piezoelectrically active waves in any structure including at
      least one piezoelectric layer. Acoustic modes that are not piezoelectrically
      active and those in non-piezoelectric materials can be also obtained by using the
      intermediate results, such as derived GSI matrices.

PMID- 11570773
TI  - A finite element analysis of the time-delay periodic ring arrays for guided wave
      generation and reception in hollow cylinders.
AB  - A new guided wave transducer model, time-delay periodic ring arrays (TDPRAs), is
      proposed and investigated in this paper for guided cylindrical wave generation
      and reception in hollow cylinders with application interests focusing on non
      destructive testing (NDT) of piping/tubing. A finite element simulation has been
      performed for axisymmetric guided-mode excitation and reception with TDPRAs. By
      arranging a proper configuration of the time-delay profile and the electric
      connection pattern of a ring array, unidirectional excitation and reception of
      guided waves can be achieved. The numerical results are obtained for the first
      three axisymmetrical modes and are compared with respect to generation efficiency
      and mode selectivity. Parametric influences on the performance of TDPRAs are
      discussed, combining a 2-D phase velocity-frequency spectrum approach with the
      mode dispersion and displacement structure analyses. The identification of
      converted modes in guided cylindrical wave reflections with a flexible TDPRA
      receiver has also been studied through sample notch reflection.

PMID- 11570774
TI  - Force-frequency coefficient of symmetrical incomplete circular quartz crystal
      resonator.
AB  - The changes in the resonance frequencies of the thickness-shear vibration of
      symmetrical incomplete circular AT-cut quartz crystal resonators (QXRs), which
      are used as sensing elements in digital force sensors or pressure transducers, by
      the application of diametrical forces are discussed by considering the
      piezoelectric effect and the anistropic characteristics of crystal plates. Two
      dimensional motion equations for predicting the frequency changes are derived
      from three-dimensional piezoelectricity equations, and equations deduced by
      Janiaud for solving the stress distribution in crystal plates are used to
      calculate the force-frequency coefficients of incomplete circular resonators. The
      results show that the piezoelectric effect of crystal plates decreases the force
      frequency coefficient of the azimuth angle 0 degrees by 7% as compared with no
      piezoelectricity assumption. The incomplete circular shape can be applied to a
      larger load than the circular disc because the flat regions of the incomplete
      shape provide a distributed load application without the problems of stress
      concentration of a point force inherent to a circular disc. The incomplete shape
      gives an increased force sensitivity when compared with the complete disc near
      azimuth angle 0 degrees. The theoretical curves agree well with Ratajski's
      experimental results.

PMID- 11570775
TI  - Occupational inhalant exposure and respiratory disorders among never-smokers
      referred to a hospital pulmonary function laboratory.
AB  - BACKGROUND: Multiple reports have described associations between occupational
      inhalant exposure and lung disease. Previous occupational lung disease
      investigations have studied populations consisting of both smokers and
      nonsmokers. Smoking complicates interpretation of toxicant exposure-response
      relationships. The objective of this study was to determine whether, among never
      smokers, occupational exposure to gases, dusts, or fumes is associated with a
      history of respiratory disorders and pulmonary function test defined obstructive
      lung disease. METHODS: We performed a retrospective analysis of 517 never-smoker
      patients who underwent pulmonary function testing in our clinical laboratory
      between 1986 and 1999. We calculated the relative risks of developing adverse
      respiratory health outcomes given a history of exposure to occupational
      inhalants. RESULTS: Compared with persons with a negative occupational exposure
      history, exposed persons had an increased risk of reporting a history of
      bronchitis [relative risk (RR), 1.59; 95% confidence interval (CI), 1.20-2.12],
      recurrent lung infections (RR, 2.09; 95% CI, 1.14-3.82), and bronchodilator use
      (RR, 1.61; 95% CI, 1.26-2.06). There was also a statistically significant
      association between a history of inhalant exposure and the finding of an
      obstructive ventilatory defect on pulmonary function testing (RR, 1.79; 95% CI,
      1.12-2.85). A history of inhalant exposure was not associated with self-reported
      asthma (RR, 1.08; 95% CI, 0.83-1.41). The population attributable risk estimates
      for respiratory disorders due to inhalant exposure were: bronchitis, 23.6%;
      recurrent lung infection, 36.3%; bronchodilator use, 24.3%; and obstructive lung
      disease, 29.6%. CONCLUSIONS: Occupational inhalant exposure is a strong risk
      factor for lung disease in this population of never smokers. A significant burden
      of respiratory disease in this population may be attributable to occupational
      inhalant exposure.

PMID- 11570776
TI  - Pulmonary function in patients with diabetes mellitus.
AB  - BACKGROUND: Pulmonary complications of diabetes mellitus have been poorly
      characterized. Although some authors have reported normal pulmonary function,
      others found abnormalities in lung volumes, pulmonary mechanics, and diffusing
      capacity. SUBJECTS AND METHODS: We studied pulmonary function in a group of
      patients with diabetes using a combined cardiopulmonary exercise test. Twenty
      seven patients with diabetes aged 48 +/- 13 years participated in the study.
      RESULTS: Overall, forced vital capacity, forced expiratory volume in 1 second,
      and forced expiratory flow, midexpiratory phase, were within the predicted
      values, but the residual volume/total lung capacity ratio was slightly elevated.
      Comparison by diabetes type showed nonsignificant differences in forced
      expiratory volume in 1 second and forced expiratory flow, midexpiratory phase.
      Residual volume/total lung capacity ratio was significantly elevated in type 1
      patients compared with type 2. Carbon monoxide diffusion capacity (DLCO) was
      normal in both groups. There was no correlation between the results on pulmonary
      function test and duration of disease, presence of microangiopathy, or glycemic
      control. The DLCO was significantly lower in patients with microangiopathic
      changes, but not when DLCO was corrected for alveolar volume. On the
      cardiopulmonary exercise test, maximal workload, maximum oxygen uptake, and
      maximal heart rate were less than predicted, whereas anaerobic threshold and
      ventilatory reserve were normal. No significant differences were noted in
      diabetes type, and there was no correlation between parameters of cardiopulmonary
      exercise test and the other variables. CONCLUSION: Spirometric values are
      preserved in patients with diabetes mellitus, and there are no defects in
      diffusing capacity. Cardiovascular factors may account for impaired physical
      performance. There is no need for routine screening of pulmonary function among
      diabetic patients.

PMID- 11570777
TI  - Calculation of the estimated creatinine clearance in avoiding drug dosing errors
      in the older patient.
AB  - BACKGROUND: The population of hospitalized older patients is increasing. We
      investigated whether clinicians accurately detected renal insufficiency in older
      patients and chose correct doses of commonly prescribed antibiotics. METHODS: We
      conducted a retrospective chart review of 1044 patients > 80 years admitted to
      the University of California Davis Medical Center between January and December
      1997 with a diagnosis of infection. Inclusion criteria included data necessary to
      calculate creatinine clearance using the Cockroft-Gault equation and
      administration of any of the study antibiotics. Patients with unstable renal
      function, defined as an increase in creatinine of > or = 1.0 mg/dL/day were
      excluded. Administered dosages of each study drug were compared with the
      appropriate adjusted doses. We examined the variables of age, weight, serum
      creatinine, and sex to determine whether any were individually predictive of
      dosing errors. RESULTS: Dosing errors were identified in all of the antibiotics
      studied, and the overall dosing error rate was 34%. The factors that were
      predictive of dosage errors were advanced age and low body weight. Serum
      creatinine and sex were not statistically significant factors. CONCLUSIONS:
      Widespread errors in medication dosing are made in elderly hospitalized patients.
      The Cockroft-Gault equation reveals significant renal insufficiency requiring
      dose adjustments in most elderly patients studied, especially those > 85 years of
      age and with low body weight. Estimation of glomerular filtration rate should be
      performed routinely on all admitted patients older than 80 and in any patient
      with low lean body mass.

PMID- 11570778
TI  - Blepharoclonus, pseudoasterixis, and restless feet.
AB  - OBJECTIVE: To report a syndrome in 30 patients characterized by headache,
      myoclonic tremors of the eyelids (blepharoclonus), action tremors of the hands on
      flexion-extension movements at the wrists simulating asterixis (pseudoasterixis)
      and habitual diurnal movements of the feet. Ten patients are described in detail.
      METHODS: Clinical history, neurologic examination, computed tomography of the
      head, magnetic resonance imaging of the brain, electroencephalogram,
      electromyogram, and nerve conduction velocities. Headaches were diagnosed
      according to the International Headache Society classification. A retrospective
      uncontrolled review of the cases collected by the author was completed. RESULTS:
      Seven patients had migraine with aura and 8 without aura; 3 had both migraine and
      tension headache, 11 had tension headache, 2 had cluster headache, and 1 had
      idiopathic stabbing headache. None of the patients had tumoral lesions or
      vascular malformations of the brain. Eight of the subjects had history of
      somnambulism and 9 had family history of somnambulism. Restless legs syndrome was
      present in 8 patients in addition to restless feet. Some evidence of axonal
      peripheral neuropathy was present in 13 patients. CONCLUSION: This report
      supports the notion that in certain cases, an association exists between
      headache, involuntary movement disorders, and peripheral neuropathy. Additional
      studies are needed to elucidate the pathogenesis of this syndrome.

PMID- 11570779
TI  - Nonspecific human IgG reduces survival in neonatal rats infected with Escherichia
      coli.
AB  - BACKGROUND: Human intravenous IgG (IVIG) containing specific antibodies protects
      neonatal rats from septic death. However, IVIG has immunosuppressive properties
      and clinical trials of IVIG in neonates at risk for sepsis have yielded
      conflicting results. HYPOTHESIS: This study was designed to test the hypothesis
      that nonspecific antibodies in IVIG reduce survival in neonatal rats infected
      with Escherichia coli. METHODS: Specific antibodies were adsorbed from IVIG with
      E. coli to produce IVIG/anti-E. coli-. After transthoracic administration of E.
      coli, survival was determined in neonatal rats injected intraperitoneally with
      phosphate-buffered saline, IVIG/anti-E. coli- (500 mg/kg) or IVIG containing anti
      E. coli antibodies (IVIG/anti-E. coli+). Complement-mediated hemolytic activity
      of neonatal rat serum was quantified using sensitized sheep erythrocytes.
      RESULTS: Compared with placebo, intraperitoneal IVIG/anti-E. coli- reduced
      neonatal survival after E. coli infection. In contrast, IVIG/anti-E. coli+
      protected infected animals. Both IVIG/anti-E. coli- and IVIG/anti-E. coli+
      impaired the complement-mediated hemolytic activity of neonatal rat serum.
      CONCLUSIONS: IVIG contained (1) nonspecific antibodies that reduced survival in
      neonatal rats infected with E. coli and (2) protective anti-E. coli antibodies
      that enhanced survival in neonatal rats infected with E. coli. We speculate that
      in clinical trials of IVIG to treat or prevent neonatal sepsis, inconsistent
      results may be caused, in part, by lot-to-lot variations in the ratio of
      immunosuppressive, nonspecific antibodies to protective, specific antibodies.

PMID- 11570781
TI  - A 78-year-old man with pancytopenia and abnormal lymphocytes.

PMID- 11570780
TI  - "There is power in the blood": a case discussing ethical issues of utility of
      resources.
AB  - The allocation of medical resources is often a great concern in the United
      States. This article discusses a case concerning utility of resources in a
      patient with a terminal disease. We assert that the goals of treatment tailored
      to an individual patient should be made at the bedside by a fiduciary (physician)
      in conjunction with the patient's preferences and values. There is great
      responsibility in making these decisions and it is critical that they be made at
      the bedside with the patient and family clearly aware of the goals of treatments
      and informed of treatment limitations.

PMID- 11570782
TI  - Implantable cardioverter-defibrillator endocarditis secondary to Candida
      albicans.
AB  - The implantable cardioverter-defibrillator (ICD) represents an important advance
      in the treatment of ventricular arrhythmias, but infection has remained a serious
      complication of device implantation. Fungal infections associated with these
      devices are uncommon, with only 4 cases previously reported. We describe a case
      of ICD-associated endocarditis caused by Candida albicans that was successfully
      treated with complete device explantation and prolonged antifungal therapy, and
      we review the features of ICD-related fungal infections.

PMID- 11570783
TI  - Unusual coronary artery aneurysm and acute myocardial infarction in a middle-aged
      man with systemic lupus erythematosus.
AB  - A 55-year-old man developed acute myocardial infarction (AMI) related to a large
      coronary artery aneurysm and a distal coronary stenotic lesion after steroid
      therapy for systemic lupus erythematosus (SLE). Only 13 SLE patients with AMI
      caused by coronary artery aneurysms have been reported, 11 of whom were young or
      middle-aged women and the 2 remaining were young men. This is the first report of
      a middle-aged man with multiple coronary lesions.

PMID- 11570784
TI  - Late recurrence of lupus nephritis in a renal transplant recipient: response to
      mycophenolate mofetil.
AB  - Clinically significant recurrence of lupus nephritis in the renal allograft is
      low, with an incidence of 1 to 3%, and usually occurs within the first 6 years
      after transplantation. We report an unusual case of a patient with end-stage
      renal disease caused by lupus nephritis who received a kidney transplant from a
      living relative; 13 years later, the patient had a severe recurrence of diffuse
      proliferative lupus nephritis. The patient relapsed after receiving intravenous
      cyclophosphamide therapy and had a partial response to oral mycophenolate
      mofetil. In this report we review the risk factors for the recurrence of the
      systemic lupus erythematosus in the kidney graft and the anti-lupus activity of
      mycophenolate mofetil.

PMID- 11570785
TI  - Thrombotic thrombocytopenic purpura associated with clopidogrel administration:
      case report and brief review.
AB  - Clopidogrel has replaced ticlopidine (in the United States but not worldwide).
      Clopidogrel can either be used independently or in combination with other
      antiplatelet agents. Clopidogrel has a lower frequency of associated thrombotic
      thrombocytopenic purpura than ticlopidine, a lower rate of neutropenia, and
      better gastrointestinal tolerance. We describe a case of thrombotic
      thrombocytopenic purpura associated with the use of clopidogrel after
      percutaneous transluminal angioplasty and stent placement. Discontinuation of the
      drug and transfusion of 17 units of cryodepleted plasma resulted in resolution of
      the hematological abnormalities. Clinicians should be alert to this adverse
      effect of clopidogrel and monitor platelet counts in patients receiving it.

PMID- 11570786
TI  - Neurologic problems associated with chronic nitrous oxide abuse in a non
      healthcare worker.
AB  - Chronic exposure to nitrous oxide (N2O) is known to be associated with
      hematologic and neurologic abnormalities. When this syndrome occurs, it is
      generally seen in health care workers, especially dentists and anesthesiologists,
      who have access to nitrous oxide. Here, however, we report a case of a 55-year
      old non-healthcare worker who presented with multiple neurological abnormalities.
      His serum vitamin B12 level was low but his Shilling test was normal. His
      neurologic symptoms improved after cessation of inhaling nitrous oxide and
      starting vitamin B12 therapy. Physicians should consider nitrous oxide abuse in
      non-healthcare workers presenting with neurologic symptom of unclear cause.

PMID- 11570787
TI  - FAWC calls for greater clarity on farm assurance schemes.

PMID- 11570788
TI  - Prevalence, incidence, signs and treatment of clinical listeriosis in dairy
      cattle in England.
AB  - The prevalence, incidence and clinical signs of listeriosis in dairy cattle in
      England were investigated by means of a postal questionnaire survey of 1500 dairy
      farmers. The response rate was 64.1 per cent. Overall the farm prevalence of
      listeriosis was 11.7 per cent, 9.3 per cent for milking cows, 5.0 per cent for
      replacement heifers and 1.4 per cent for dairy calves. The within-herd incidence
      rate per thousand animal-years was 51.4 for all cases, 39.7 for milking cows,
      86.6 for replacement heifers and 73.7 for dairy calves. Most cases of clinical
      listeriosis were reported between December and May, and the most common signs
      were silage eye, followed by nervous signs. The results of the questionnaire were
      validated internally by re-estimating the farm prevalence by including only those
      cases diagnosed by a veterinarian or veterinary investigation centre; the
      prevalence did not change significantly. The proportion of cases which were
      culled or died of encephalitic listeriosis was compared with the proportion
      diagnosed during statutory BSE reporting. The fact that the two proportions were
      similar provided external validation for the results of the questionnaire.

PMID- 11570789
TI  - Epidemiology of equine grass sickness: a literature review (1909-1999).
AB  - The geographical spread of grass sickness between 1909 and 1999, particularly in
      England and Wales, is described, and the experimental investigations to identify
      a causal agent are summarised. The epidemiological techniques used to investigate
      grass sickness vary from clinical observations, to more advanced methods such as
      case-control studies using logistic regression analyses. Several risk factors for
      grass sickness have been reported consistently (age, time of year and recent
      movement to new pasture or premises) and several others have been reported for
      which the findings remain inconsistent (weather, pasture type, breed,
      supplementary feeding and use of anthelmintics).

PMID- 11570790
TI  - Pen-side test for the diagnosis of rinderpest in Pakistan.

PMID- 11570791
TI  - Comparison of valnemulin and lincomycin in the treatment of digital dermatitis by
      individually applied topical spray.

PMID- 11570792
TI  - Simultaneous detection of porcine circovirus type 2 and porcine parvovirus in
      pigs with PMWS by multiplex PCR.

PMID- 11570793
TI  - Primary cutaneous haemangiosarcoma in a cow.

PMID- 11570794
TI  - Hypertrophic pulmonary osteopathy associated with granular cell tumour in a mare.

PMID- 11570795
TI  - Pulmonary function measurements in dolphins using capnography.

PMID- 11570796
TI  - Ethical decision-making in veterinary practice.

PMID- 11570797
TI  - Toxicosis in dogs exposed to Clostridium perfringens type A.

PMID- 11570798
TI  - Welfare movement licensing.

PMID- 11570799
TI  - Modelling control strategies for foot-and-mouth disease.

PMID- 11570800
TI  - Cryptorchidism and alopecia in cats.

PMID- 11570801
TI  - Isolation and identification of avian pneumovirus from pheasants.

PMID- 11570802
TI  - Phytoremediation of small-scale oil spills in fresh marsh environments: a
      mesocosm simulation.
AB  - Research was conducted to assess the impact of oiling on fresh-marsh plant
      communities and to test the efficacy of techniques that may be used to enhance
      the bioremediation of crude oil spills in these environments while minimizing
      secondary anthropogenic impacts. To emulate field conditions, a mesocosm facility
      was used that houses 120 mesocosm vessels, each of 200-1 capacity. A five-way
      factorial treatment arrangement was used that included two substrates (inorganic,
      organic), two nutrient regimes (fertilized, not fertilized), two aeration levels
      (substrate aeration, no aeration), three oiling concentrations (0-, 5-, 10-1 m(
      2) of South Louisiana Sweet Crude oil), and four vascular plant species
      (Alternanthera philoxeroides, Panicum hemitomon, Phragmites australis, Sagittaria
      lancifolia, and an unplanted control). Under the 5- and 10-1 m(-2) oiling
      concentrations, S. lancifolia displayed a short-term response of increased
      productivity, whereas P. hemitomon had the highest biomass production and
      photosynthetic rates at the end of the 18-month experiment. Overall plant growth
      and productivity, as well as oil degradation, were significantly higher in the
      inorganic substrate, indicating that biodegradation of oil spills in organic
      substrates may require a longer time period. Time-released fertilizer also
      stimulated plant productivity and resulted in higher soil respiratory quotients,
      suggestive of greater microbial activity, particularly in aerated mesocosms. The
      amount of oil remaining after 18 months was lowest in aerated and fertilized
      mesocosms containing either P. hemitomon or S. lancifolia and a substrate of low
      organic matter content.

PMID- 11570803
TI  - Evidence of uptake, biotransformation and DNA binding of polyaromatic
      hydrocarbons in Atlantic cod and corkwing wrasse caught in the vicinity of an
      aluminium works.
AB  - Feral Atlantic cod (Gadus morhua) and corkwing wrasse (Symphodus melops) were
      investigated for polyaromatic hydrocarbon (PAH) contamination in the Karmsund
      strait, western Norway. This strait is highly contaminated with PAHs, and a main
      source is the chronic release of gas-scrubbing effluents from a local aluminium
      works. In both species, the level of biliary PAH metabolites and hepatic DNA
      adducts were higher in fish collected near the aluminium works. Interestingly, a
      significantly higher level of both biliary PAH metabolites and hepatic DNA
      adducts was found in corkwing wrasse as compared to cod, indicating a higher
      potential for genotoxic effects in this species. Hepatic cytochrome P4501A
      (CYP1A) in cod estimated by ethoxyresorufin-O-deethylase and an immunoassay
      technique (ELISA), seemed to be weakly induced at the contaminated sites. At the
      most contaminated site, skin ulcers and fin erosion were detected in about 70 and
      45% of the cods, respectively. The data demonstrated that both cod and corkwing
      wrasse may be suitable target species for PAH pollution monitoring.

PMID- 11570804
TI  - Inhibition of marine bacteria by extracts of macroalgae: potential use for
      environmentally friendly antifouling paints.
AB  - Although a total ban on the use of TBT coatings is not expected in the short
      term, there is a growing need for environmentally safe antifouling systems. A
      search for new non-toxic antifoulants has been carried out among marine
      macroalgae. Antifouling activity of aqueous, ethanolic and dichloromethane
      extracts from 30 marine algae from Brittany coast (France) was examined in vitro
      against 35 isolates of marine bacteria. About 20% of the extracts were found to
      be active. The high levels of inhibitory activities against bacteria recorded in
      some extracts and the absence of toxicity on the development of oyster and sea
      urchin larvae and to mouse fibroblast growth suggests a potential for novel
      active ingredients in antifouling preparations.

PMID- 11570805
TI  - Intersex and sterility in the periwinkle Littorina littorea (Mollusca:
      Gastropoda) along the Western Scheldt estuary, The Netherlands.
AB  - In this study we present the results of an intersex survey of Littorina littorea
      along the heavily polluted Western Scheldt estuary (the Netherlands), and record
      for the first time the intersex phenomenon in L. littorea from Dutch waters.
      Intersex differed significantly between localities and was the highest in the
      vicinity of the harbours of Antwerp and Vlissingen, as reflected by the I

PMID- 11570806
TI  - Effects of molting and environmental factors on trace metal body-burdens and
      hemocyanin concentrations in the American lobster, Homarus americanus.
AB  - Hemocyanin concentrations in the hemolymph of marine crustacea are dependent on
      the molt cycle and on environmental conditions. Studies in our laboratories have
      found that hemocyanin levels in blue crabs are reduced after ecdysis and under
      conditions of environmental stress (Engel, Brouwer, & McKenna, 1993. Hemocyanin
      concentrations in marine crustaceans as a function of environmental conditions.
      Marine Ecology Progress Series, 93, 233-244). We have extended those studies to
      include the American lobster, Homarus americanus. Hemolymph and digestive gland
      tissues from Long Island Sound lobsters were analyzed for hemocyanin, copper, and
      zinc during different stages of the molt cycle. Hemocyanin, copper and zinc in
      the hemolymph were highest in premolt stages (D1-D4), and lowest in the
      postecdysal papershell stages (B1-B2). Concomitantly, copper in digestive glands
      decreased significantly following ecdysis, but no significant changes in the
      metals bound to metallothionein (MT) were observed. Copper-MT was the predominant
      form throughout the molt cycle, presumably because lobsters were obtained from
      copper-contaminated areas. To examine the effects of environmental factors,
      intermolt lobsters were collected from locations of different environmental
      quality along the Atlantic coast, and were analyzed for hemocyanin and trace
      metals. In general, animals from areas with a history of contamination showed the
      highest hemocyanin concentrations.

PMID- 11570807
TI  - Concentration and toxic potential of polychlorinated biphenyl congeners in
      migratory oceanic birds from the North Pacific and the Southern Ocean.
AB  - Concentrations of PCBs and their toxic potential were examined in subcutaneous
      fat of eight albatross and one petrel species collected from the North Pacific
      and the Southern Oceans. Among all the species analyzed, high PCB levels were
      found in adult male blackfooted albatross from the North Pacific with the mean
      value of 92 microg/g wet weight. No significant gender difference in PCB
      accumulation was observed (P>0.1). The mean PCB levels in Southern Oceanic birds
      were 1 or 2 orders of magnitude lower than those from the North Pacific
      albatrosses. A regional-specific accumulation of non-ortho coplanar congeners
      were observed, most birds from the Southern Ocean had higher IUPAC 169 levels
      while IUPAC 126 concentrations were higher in those from the North Pacific. The
      estimated toxic equivalents for black-footed and Laysan albatrosses from the
      North Pacific were in the same range of some fish-eating birds, which were highly
      contaminated by PCBs. The correlation between ratio of IUPAC 169/126
      concentration and total PCBs concentration indicated the possibility of induction
      in cytochrome P450 activities in North Pacific albatrosses (P<0.01). The
      calculated hazard indices indicated that black-footed and Laysan albatrosses
      inhabiting in the North Pacific had similar threshold levels which were known to
      cause toxic effects in some populations of fish-eating birds.

PMID- 11570808
TI  - Effects of the multiple stressors copper and reduced salinity on the metabolism
      of the hermatypic coral Porites lutea.
AB  - This study investigates the physiological responses in the hermatypic coral
      Porites lutea when exposed to a combination of reduced salinity (from ambient 30
      psu to 20 psu) and two concentrations of copper (CuS04), 10 microg 1(-1) and 30
      microg 1(-1). Corals were exposed for 14 h and changes in metabolism in terms of
      primary production rate per chlorophyll a and respiration per surface area (cm2)
      were used as measures of stress. The results showed no significant changes in
      respiration rate in any of the treatments compared with controls, or between
      treatments. The primary production rate, however, displayed a more complex
      pattern. Corals exposed to reduced salinity, 30 microg 1(-1) copper, and the
      combination of the two stressors significantly reduced the production rate,
      whereas corals exposed to 10 microg 1(-1) only, remained unaffected. However,
      adding 10 microg 1(-1) copper to reduced salinity did not affect the production
      rate thus indicating an antagonistic effect.

PMID- 11570809
TI  - T-kininogen inhibits fibroblast proliferation in the G(1) phase of the cell
      cycle.
AB  - By using synthetic protease inhibitors, several investigators have demonstrated
      that cysteine proteinases are required for cell proliferation. Kininogens are
      potent and specific physiological inhibitors of cysteine proteinases. We have
      used several mouse fibroblast-derived cell lines that express biologically active
      T-kininogen under the control of the mouse metallothionein promoter to test its
      effect on cell proliferation. Our results indicate that expression of T-kininogen
      results in diminished proliferative capacity, as measured by reduced cell
      numbers, both in logarithmically growing cultures and in G(0) cells induced to
      proliferate in response to serum. Furthermore, both fluorescence-activated cell
      sorting (FACS) analysis and incorporation of radioactive precursors into DNA
      suggest that the cells are unable to progress from G(0) through the S phase of
      the cell cycle in response to serum stimulation. However, we find that T
      kininogen-expressing cell lines are still capable of responding to growth factors
      present in the serum, both by activating the ERK pathway and by expressing early
      genes, such as c-Fos and c-Jun. Thus, our results suggest that inhibition of
      cysteine proteinases by T-kininogen leads to inhibition of cell proliferation
      between the G(1) and S phases of the cell cycle.

PMID- 11570810
TI  - Signaling and subcellular localization of the TNF receptor Edar.
AB  - Tabby and downless mutant mice have identical phenotypes characterized by
      deficient development of several ectodermally derived organs such as teeth, hair,
      and sweat glands. Edar, encoded by the mouse downless gene and defective in human
      dominant and recessive forms of autosomal hypohidrotic ectodermal dysplasia (EDA)
      syndrome, is a new member of the tumor necrosis factor (TNF) receptor
      superfamily. The ligand of Edar is ectodysplasin, a TNF-like molecule mutated in
      the X-linked form of EDA and in the spontaneous mouse mutant Tabby. We have
      analyzed the response of Edar signaling in transfected cells and show that it
      activates nuclear factor-kappaB (NF-kappaB) in a dose-dependent manner. When Edar
      was expressed at low levels, the NF-kappaB response was enhanced by coexpression
      of ectodysplasin. The activation of NF-kappaB was greatly reduced in cells
      expressing mutant forms of Edar associated with the downless phenotype.
      Overexpression of Edar did not activate SAPK/JNK nor p38 kinase. Even though Edar
      harbors a death domain its overexpression did not induce apoptosis in any of the
      four cell lines analyzed, nor was there any difference in apoptosis in developing
      teeth of wild-type and Tabby mice. Additionally, we show that the subcellular
      localization of dominant negative alleles of downless is dramatically different
      from that of recessive or wild-type alleles. This together with differences in NF
      kappaB responses suggests an explanation for the different mode of inheritance of
      the different downless alleles.

PMID- 11570811
TI  - Poly(ADP-ribose) polymerase cleavage during apoptosis: when and where?
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) plays the active role of "nick sensor"
      during DNA repair and apoptosis, when it synthesizes ADP-ribose from NAD(+) in
      the presence of DNA strand breaks. Moreover, PARP-1 becomes a target of apoptotic
      caspases, which originate two proteolytic fragments of 89 and 24 kDa. The precise
      relationship between PARP-1 activation and degradation during apoptosis is still
      a matter of debate. In human Hep-2 cells driven to apoptosis by actinomycin D, we
      have monitored PARP-1 activity by the mAb 10H, which is specific for the ADP
      ribose polymers, and we have observed that poly(ADP-ribose) synthesis is a very
      early response to the apoptotic stimulus. The analysis of the presence and fate
      of the p89 proteolytic fragment revealed that PARP-1 proteolysis by caspases is
      concomitant with poly(ADP-ribose) synthesis and that p89 migrates from the
      nucleus into the cytoplasm in late apoptotic cells with advanced nuclear
      fragmentation.

PMID- 11570812
TI  - Ethanol-induced apoptosis in hepatoma cells proceeds via intracellular Ca(2+)
      elevation, activation of TLCK-sensitive proteases, and cytochrome c release.
AB  - Ethanol is known to induce apoptosis in hepatocytes. However, intracellular
      signaling events of ethanol-induced death are still only partially understood. We
      studied such processes in ethanol-induced apoptosis in HepG2 cells as a model
      system for human liver cells. We determined the incidence of apoptosis by DNA
      fragmentation and tested the effects of various known inhibitors. Ethanol induces
      apoptosis in HepG2 cells in a dose- and time-dependent manner as well as in rat
      primary hepatocytes. This effect was not mediated through the death receptor CD95
      and the tumor necrosis factor receptors. It was efficiently inhibited by the
      caspase inhibitor N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone (zVAD
      fmk), the Ca(2+) chelator EGTA, and the serine protease inhibitor N-p-tosyl-l
      lysine chloromethyl ketone (TLCK). Upon ethanol treatment, the intracellular
      calcium ion concentration was increased and cytochrome c was released from the
      mitochondria, and caspases were activated. EGTA and TLCK could inhibit cytochrome
      c release from the mitochondria. Furthermore, overexpression of Bcl-x(L) saved
      cells from ethanol-induced apoptosis. These data suggest that ethanol-induced
      apoptosis in liver cells is initiated by the intracellular Ca(2+) elevation in
      the cytoplasm and activation of TLCK-sensitive serine proteases. Our data provide
      new insight into ethanol-induced apoptosis in liver cells and may lead to
      therapeutic strategies to prevent liver damage.

PMID- 11570813
TI  - Cell-type-specific expression of the TFIID component TAF(II)135 in the nervous
      system.
AB  - A number of nervous system-specific enhancers and silencers have been isolated
      and characterized. However, the detailed mechanism of cell- and tissue-specific
      regulation of transcription is to a large extent unknown and the role of the
      basal transcriptional complex components in these processes is mostly unclear.
      Here we demonstrate that mRNA levels of TATA binding protein-associated factor
      TAF(II)135 are upregulated in neuronal cells during development. In addition,
      induction of neuronal differentiation of teratocarcinoma PCC7 cells results in
      dramatic induction of TAF(II)135 mRNA levels and activation of a variety of
      promoters. The stimulation of promoter activity in differentiating cells is
      mimicked by the overexpression of TAF(II)135. As neuronal differentiation
      requires changes in the general pattern of transcriptional activity, we suggest
      that increased levels of TAF(II)135 facilitate the induction of a large number of
      neuronal genes.

PMID- 11570814
TI  - Sodium nitroprusside-induced mitochondrial apoptotic events in insulin-secreting
      RINm5F cells are associated with MAP kinases activation.
AB  - Exposure of insulin-secreting RINm5F cells to the chemical nitric oxide donor
      sodium nitroprusside (SNP) resulted in apoptotic cell death, as detected by
      cytochrome c release from mitochondria and caspase 3 activation. SNP exposure
      also leads to phosphorylation and activation of enzymes involved in cellular
      response to stress such as signal-regulated kinase 2 (ERK2) and c-Jun NH(2)
      terminal kinase 46 (JNK46). Both cytochrome c release and caspase 3 activation
      were abrogated in cells exposed to MEK and p38 inhibitors. Treatment of cells
      with the NO donors SNP, DETA-NO, GEA 5024, and SNAP resulted in phosphorylation
      of the antiapoptotic protein Bcl-2, which was resistant to blockade of MEK, p38,
      and JNK pathways and sensitive to phosphoinositide 3-kinase (PI3K) inhibition. In
      addition, transient transfection of cells with the wild-type PI3K gamma gene
      mimics the increased rate of Bcl-2 phosphorylation detected in NO-treated cells.
      The generation of phosphoinositides seems to participate in the process since Bcl
      2 phosphorylation was not observed in cells overexpressing lipid-kinase-deficient
      PI3Kgamma. The potential of SNP toxicity directly from NO was supported by our
      finding that the NO scavenger carboxy-PTIO prevented cell death. We found no
      evidence to support the contention that oxygen radicals generated during cellular
      SNP metabolism mediate cell toxicity in RINm5F cells, since neither addition of
      catalase/superoxide dismutase nor transfection with superoxide dismutase
      prevented SNP-induced cell death. Thus, we propose that exposure to apoptotic
      concentrations of NO triggers ERK- and p38-dependent cytochrome c release,
      caspase 3 activation, and PI3K-dependent Bcl-2 phosphorylation.

PMID- 11570815
TI  - The A3 adenosine receptor as a new target for cancer therapy and chemoprotection.
AB  - Adenosine, a purine nucleoside, acts as a regulatory molecule, by binding to
      specific G-protein-coupled A(1), A(2A), A(2B), and A(3) cell surface receptors.
      We have recently demonstrated that adenosine induces a differential effect on
      tumor and normal cells. While inhibiting in vitro tumor cell growth, it
      stimulates bone marrow cell proliferation. This dual activity was mediated
      through the A3 adenosine receptor. This study showed that a synthetic agonist to
      the A3 adenosine receptor, 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyl
      uronamide (Cl-IB-MECA), at nanomolar concentrations, inhibited tumor cell growth
      through a cytostatic pathway, i.e., induced an increase number of cells in the
      G0/G1 phase of the cell cycle and decreased the telomeric signal. Interestingly,
      Cl-IB-MECA stimulates murine bone marrow cell proliferation through the induction
      of granulocyte-colony-stimulating factor. Oral administration of Cl-IB-MECA to
      melanoma-bearing mice suppressed the development of melanoma lung metastases
      (60.8 +/- 6.5% inhibition). In combination with cyclophosphamide, a synergistic
      anti-tumor effect was achieved (78.5 +/- 9.1% inhibition). Furthermore, Cl-IB
      MECA prevented the cyclophosphamide-induced myelotoxic effects by increasing the
      number of white blood cells and the percentage of neutrophils, demonstrating its
      efficacy as a chemoprotective agent. We conclude that A3 adenosine receptor
      agonist, Cl-IB-MECA, exhibits systemic anticancer and chemoprotective effects.

PMID- 11570816
TI  - VE-cadherin-derived cell-penetrating peptide, pVEC, with carrier functions.
AB  - Cell-penetrating peptides, CPPs, have been shown to translocate into living cells
      by a receptor-independent mechanism and to carry macromolecules over the plasma
      membrane. This article reports studies of the internalization of pVEC, an 18
      amino acid-long peptide derived from the murine sequence of the cell adhesion
      molecule vascular endothelial cadherin, amino acids 615-632. Fluorophore-labeled
      pVEC entered four different cell lines tested: human aortic endothelial cells,
      brain capillary endothelial cells, Bowes melanoma cells, and murine brain
      endothelial cells. In order to evaluate the translocation efficiency of pVEC, we
      performed a side-by-side comparison with penetratin, a well-characterized CPP.
      The cellular uptake of pVEC was highest for murine brain endothelial cells. All
      cell lines tested contained equal or slightly higher concentrations of pVEC than
      penetratin. pVEC mainly accumulated in nuclear structures but was also found
      throughout the cells. Furthermore, pVEC functioned as a transporter of both a
      hexameric peptide nucleic acid molecule of 1.7 kDa and a 67-kDa protein,
      streptavidin-FITC, and cellular uptake of fluorophore-labeled pVEC took place at
      4 degrees C, suggesting a nonendocytotic mechanism of translocation. In
      conclusion, our results indicate that pVEC is efficiently and rapidly taken up
      into cells and functions as a potent carrier peptide.

PMID- 11570817
TI  - Block of a mitochondrial-mediated apoptotic pathway in Tax-expressing murine
      fibroblasts.
AB  - Although the viral transactivator Tax has been established as an essential
      effector of HTLV-I-mediated oncogenesis, its exact role(s) in the pathogenesis of
      HTLV-I-associated diseases, which include both a neurodegenerative pathology and
      leukemia/lymphoma, remains to be clarified. It was recently advanced that
      dysregulation of the apoptotic process can lead to pathophysiological changes
      which result in either degenerative diseases or cancer. As the apoptotic
      potential of Tax is still debated, we addressed this question by testing the
      susceptibility of Tax(+) and Tax(-) murine fibroblasts to apoptosis under
      conditions of growth factor withdrawal or treatment with TNFalpha, which trigger
      apoptosis through different pathways, i.e., mitochondrial and receptor-mediated
      pathways, respectively. Results showed that Tax-expressing cells are protected
      from apoptotic death induced by serum deprivation but are sensitive to TNFalpha
      mediated apoptosis, suggesting that Tax expression has different effects on cell
      death, depending on the apoptotic stimulus used. Analysis of the mechanism(s)
      involved in the resistance to serum depletion-induced apoptosis indicated that
      Tax(+) cells do not undergo release of cytochrome c from the mitochondrial
      intermembrane space or redistribution of Bax from the cytosol to mitochondria,
      two phenomena critical to the mitochondrial apoptotic pathway.

PMID- 11570818
TI  - Detection of the presenilin 1 COOH-terminal fragment in the extracellular
      compartment: a release enhanced by apoptosis.
AB  - Mutations in gene encoding presenilin 1 (PS1) are responsible for the majority of
      familial Alzheimer's disease (FAD) cases. We studied PS1 localization in HEK293
      cells and in primary neurons obtained from rat cortex and hippocampus. We first
      demonstrated that PS1-CTF, but neither PS1-FL nor PS1-NTF, is released into the
      medium as a soluble and membrane-associated form. After induction of apoptosis
      with staurosporine (Sts), we observed a dramatic increase in the level of PS1-CTF
      in the medium, both in HEK293 and in primary neurons. Immunocytochemical analysis
      suggested that the release of PS1-CTF might occur via membrane shedding. Abeta(1
      42) treatment reduced PS1-CTF extracellular levels. This decrease was strongly
      associated to an impaired secretion of sAPP fragments, thus suggesting a role of
      PS1-CTF in the control of trafficking and generation of APP fragments.

PMID- 11570819
TI  - Species-specific and conserved epitopes on mouse and human E-selectin important
      for leukocyte adhesion.
AB  - Selectins are C-type, cell surface lectins that are key players in leukocyte
      adhesion to the blood vessel wall endothelium. We describe here epitopes for a
      series of novel monoclonal antibodies (moAbs), UZ4-UZ7, directed against mouse E
      selectin. All four antibodies specifically bind to mouse E-selectin, but not to P
      or L-selectin, and all inhibit the adhesion of granulocytes, peripheral blood
      lymphocytes, and promyelocytic HL-60 cells to cytokine-activated mouse
      endothelium. Three moAbs, UZ5, UZ7, and UZ6, specifically inhibit mouse E
      selectin-mediated adhesion by binding to epitopes in domains CR1 or CR2. moAb UZ4
      inhibits leukocyte adhesion to both human and murine endothelium activated with
      IL-1 or other proinflammatory stimuli. UZ4 is the first described moAb that
      detects an epitope in the lectin domain which is conserved in both murine and
      human E-selectin (CXKKKL), but is not present in the other members of the
      selectin family, P- and L-selectin. Interestingly, UZ5, UZ6, and UZ7 more
      efficiently interfere with lymphocyte than with granulocyte adhesion to cytokine
      activated endothelium, while UZ4 completely blocks adhesion of PMN, lymphocytes,
      and HL-60 and U937 cell lines. The data suggest that E-selectin-ligand engagement
      differs between lymphocytes and PMN, and that these differences may be
      accentuated by the CR1 and CR2 domains in the E-selectin cell adhesion molecule.

PMID- 11570820
TI  - Four casein kinase I isoforms are differentially partitioned between nucleus and
      cytoplasm.
AB  - The casein kinase I (CKI) family consists of at least seven vertebrate genes,
      some of which can be alternatively spliced. Previously, we have studied the four
      splice variants of the chicken CKIalpha gene. The four proteins differ only by
      the presence or absence of two peptides, a 28-amino-acid "L" insert in the
      catalytic domain and a 12-amino-acid "S" insert near the extreme C-terminus. Here
      cells were transfected with DNA encoding all four isoforms fused to the green
      fluorescent protein (GFP) and the localization of each protein was examined. We
      noted that the L insert includes the sequence PVGKRKR, which has the
      characteristics of a nuclear localization signal (NLS), and we show that the
      CKIalphaL and CKIalphaLS isoforms which contain this sequence are targeted to the
      nucleus, where a fraction becomes associated with nuclear speckles. In contrast
      the two isoforms lacking the L insert remain predominantly cytoplasmic. Mutation
      of the first lysine in the putative NLS to asparagine prevented the nuclear entry
      of GFP-CKIalphaL. Therefore different CKIalpha isoforms are targeted to different
      cellular compartments in a fashion modulated by alternate transcription and in
      these locations presumably phosphorylate and regulate different cellular
      substrates.

PMID- 11570822
TI  - MyoD activity upregulates E2F1 and enhances transcription from the cyclin E
      promoter in differentiating myoblasts lacking a functional retinoblastoma
      protein.
AB  - We investigated the mechanism leading to cyclin E accumulation when cultured
      mouse myoblasts, lacking functional Rb because of sequestration or deletion, are
      exposed to differentiating conditions (mitogen subtraction and cell-cell
      contact), which activate MyoD and normally downregulate factors involved in cell
      division. After excluding that stabilization might account for the observed
      cyclin-E mRNA accumulation, we found an induction of the cyclin-E promoter that
      correlated with E2F activity upregulation and depended on both MyoD activation
      and Rb inactivation. Analyses of the E2F1-promoter activity, in normal and Rb
      deficient fibroblasts converted by MyoD, identified a MyoD function stimulating
      E2F1 expression. The E2F1 induction was very manifest in the Rb-/- cells, but
      also detectable, at the early stage of differentiation, in normal cells. Its
      effects, although not indispensable for myogenesis, presumably contribute to
      raise the concentration of Rb-E2F1 transcription-repressing complexes, since MyoD
      strongly induces also Rb in differentiating myocytes. The activity of an E2F1
      promoter lacking the E2F sites indicated that E2F1 itself underwent self
      repression by such mechanism at late stages of differentiation. In the absence of
      Rb, however, the induced E2F1 is left with only its activating role, reversing
      the normal effect of this MyoD function.

PMID- 11570821
TI  - Lack of Elk-1 phosphorylation and dysregulation of the extracellular regulated
      kinase signaling pathway in senescent human fibroblast.
AB  - Replicative senescence is characterized by numerous phenotypic alterations
      including the loss of proliferative capacity in response to mitogens and numerous
      changes in gene expression including impaired serum inducibility of the immediate
      early genes c-fos and erg-1. Transcription of c-fos in response to mitogens
      depends on the activation of a multiprotein complex formed on the c-fos serum
      response element (SRE), which includes the transcription factors SRF (serum
      response factor) and TCF (ternary complex factor). Our data indicate that at
      least two defects are responsible for the decreased c-fos transcription in
      senescent cells, one caused by diminished DNA binding activity of the SRF and
      another resulting from impaired activation of the TCF, Elk-1. In nuclei isolated
      from serum stimulated senescent cells the activating phosphorylation of
      p62(TCF)/Elk-1, which is catalyzed by the members of the extracellular-regulated
      kinase (ERK) family was strikingly diminished and correlated with a decrease in
      the abundance of activated ERK proteins. In contrast, in total cell lysates ERK
      phosphorylation and ERK activity (normalized to total protein) reached similar
      levels following stimulation of early- and late-passage cells. Interestingly,
      senescent cells consistently exhibited higher ERK protein abundance. Thus, the
      proportion of phosphorylated (active) ERK molecules in stimulated senescent cells
      was lower than in early passage cells. The accumulation of unphosphorylated ERK
      molecules in senescent cells correlated with the diminished abundance of
      phosphorylated (active) MEK. These data indicate that in senescent cells there is
      a general dysregulation in the ERK signaling pathway, which results in the
      accumulation of inactive ERK molecules, decreased abundance of active ERK in the
      nucleus of senescent cells, and subsequent lack of activation of the
      transcription factor TCF(Elk-1). These impairments, together with the impaired
      DNA binding activity of SRF, could potentially account for the lack of c-fos
      expression in senescent cells and for multiple other molecular changes dependent
      upon this pathway.

PMID- 11570823
TI  - Transcription activating property of autoantigen SG2NA and modulating effect of
      WD-40 repeats.
AB  - Autoantibodies to intracellular proteins have been detected in sera of patients
      with various forms of cancer. Nuclear autoantigen SG2NA (S, G2 phase nuclear
      antigen) was isolated using autoantibodies from a patient with bladder and lung
      cancers and its expression is enhanced in the S and G2 phases of the cell cycle.
      Molecular cloning revealed that the C-terminal region of SG2NA contains six WD-40
      repeats, motifs that are present in a large family of proteins with diverse
      functions. We show that the N-terminal region of SG2NA (aa 1-391) acted as a
      strong transcriptional activator in both yeast and mammalian cells. In contrast,
      the C-terminal WD-40 repeats had an inhibitory effect on transcription
      activation. We performed molecular swapping experiments by substituting the WD-40
      repeats of SG2NA with those of yeast Met30 and Cdc4 and showed that the WD-40
      regions from either Met30 or Cdc4 were capable of reproducing transcription
      repression function. The SG2NA WD-40 repeats were also able to repress basal
      level transcription and transactivation function of a GAL4-VP16 chimera. These
      observations suggest that some WD-40 repeats may have, as one of their functions,
      a negative regulatory role in the biological activities of their own and perhaps
      other proteins.

PMID- 11570824
TI  - Apical to basolateral transcytosis and apical recycling of immunoglobulin G in
      trophoblast-derived BeWo cells: effects of low temperature, nocodazole, and
      cytochalasin D.
AB  - The murine neonatal Fc receptor, FcRn, carries out two functions: materno-fetal
      IgG delivery and maintenance of serum IgG homeostasis. During human pregnancy
      maternal IgG is transferred across placental syncytiotrophoblasts presumably by
      the human homolog of FcRn, hFcRn. Trophoblast-derived BeWo cells express hFcRn
      endogenously and can be considered as a model system to investigate IgG transport
      in syncytiotrophoblasts. Using a pulse-chase protocol, we here demonstrate that
      polarized BeWo cells exhibit not only apical to basolateral transcytosis but also
      apical IgG recycling. Thus, for the first time we demonstrate that epithelial
      cells can be involved in both materno-fetal IgG transmission and regulation of
      serum IgG levels. Lowering the temperature from 37 to 16 degrees C reduced, but
      did not block, IgG recycling and transcytosis. Microtubule-disruption by
      nocodazole did not influence transcytosis or apical recycling. Disassembly of
      filamentous actin by cytochalasin D stimulated apical endocytosis and recycling,
      while transcytosis remained unaffected. In summary, in BeWo cells apically
      internalized IgG enters both a transcytotic and recycling pathway. While the
      transcytotic route is temperature-sensitive but independent from microtubules and
      actin filaments, the apical recycling pathway is temperature-influenced and
      stimulated by actin disassembly, suggestive for the involvement of distinct
      endosome subcompartments in transcytosis and recycling.

PMID- 11570826
TI  - Page for patients. Otitis media.

PMID- 11570825
TI  - A community-wide smoking cessation program: Quit and Win 1998 in Olmsted county.
AB  - BACKGROUND: Quit and Win is a community-wide stop smoking contest to help
      cigarette smokers stop smoking and educate the general public concerning smoking
      hazards. METHODS: All community residents, 15 years of age or older, were
      eligible to participate in either the stop smoking contest or the supporter
      contest. A random telephone survey to local households was conducted before and
      after the Quit and Win contest to assess the level of knowledge and attitude
      changes about smoking. RESULTS: Of the 304 smokers enrolled in the contest, 42%
      self-reported continuous tobacco abstinence for the 4-week contest period and 11%
      were abstinent at 1 year postcontest. Significant predictors for tobacco
      abstinence during the contest were formal education beyond high school, absence
      of other smokers in the household, having a support person enrolled in the
      support person contest, and the type of relationship that the support person had
      with their smoker. Survey results showed that this contest changed some local
      attitudes and increased general knowledge of smoking hazards. CONCLUSIONS:
      Community-wide stop smoking contests can be used to engage smokers and their
      support in the community and can be successful in reducing tobacco use.

PMID- 11570827
TI  - Trends in cigarette smoking in Spain by social class.
AB  - OBJECTIVE: . The aim of this study was to evaluate smoking trends among Spanish
      men and women by social class between 1987 and 1997. METHODS: We used secondary
      analysis of the National Health Interview Surveys of 1987, 1993, 1995, and 1997.
      The main outcome measures were prevalence of smoking, smoking cessation activity
      (quit ratio), and smoking initiation in the manual and nonmanual social class in
      each year and smoking prevalence ratio, smoking cessation ratio, and smoking
      initiation ratio in 1997 versus 1987 in each social class. RESULTS: Among men
      ages 25 years and older the prevalence of smoking in both the manual and the
      nonmanual social class decreased between 1987 and 1997 in all age groups, and the
      relative magnitude of the decrease was always greater in the nonmanual social
      class. In contrast, among women the prevalence of smoking increased in both
      social classes: in the 25- to 44-year age group the smoking prevalence ratios in
      1997 versus 1987 were 1.20 in the nonmanual social class and 1.61 in the manual
      social class, while in the 45- to 64-year age group the prevalence ratios were
      2.52 and 2.15, respectively. The quit rate among men increased in both social
      classes in all age groups between 1987 and 1997; in contrast, among women the
      quit rate increased only among those ages 25 to 44 years in the nonmanual social
      class. Smoking prevalence for people ages 16 to 24 years--smoking initiation-
      decreased among men and women between 1987 and 1997 in both social classes.
      CONCLUSIONS: Smoking trends in Spain by social class have differed among men and
      women. The findings are considered in the context of policies and programs aimed
      at reducing smoking.

PMID- 11570828
TI  - Complete diagnostic evaluation in colorectal cancer screening: research design
      and baseline findings.
AB  - BACKGROUND: While indicated by guidelines, complete diagnostic evaluation, or CDE
      (i.e., colonoscopy or combined flexible sigmoidoscopy plus barium enema X ray),
      is often not recommended and performed for persons with an abnormal screening
      fecal occult blood test (FOBT) result. We initiated a randomized trial to assess
      the impact of a physician-oriented intervention on CDE rates in primary care
      practices. METHODS: In 1998, we identified 1,184 primary care physicians (PCPs)
      in 584 practices whose patients received FOBTs that are mailed annually by a
      managed care organization screening program. A total of 470 PCPs in 318 practices
      completed a baseline survey. Practices were randomly assigned either to a Control
      Group (N = 198) or to an Intervention Group (N = 120). Control Group practices
      received the screening program. Intervention Group practices received the
      screening program and the intervention (i.e., CDE reminder-feedback plus
      educational outreach). Practice CDE recommendation and performance rates are the
      primary outcomes to be measured in the study. RESULTS: Baseline CDE
      recommendation and performance rates were low and were comparable in Control and
      Intervention Group practices (54 to 57% and 39 to 40%, respectively). PCPs in the
      practices tended to view FOBT screening and CDE favorably, but had concerns about
      screening efficacy, time involved in CDE, and patient discomfort and adherence.
      Control Group physicians were more likely than Intervention Group physicians to
      believe that a mail-out FOBT screening program helps in the practice of medicine.
      CONCLUSIONS: We were able to enroll a high proportion of targeted primary care
      practices, measure practice characteristics and CDE rates at baseline, and
      develop and implement the intervention. Study outcome analyses will take into
      account baseline differences in practice characteristics.

PMID- 11570829
TI  - The development of a decisional balance measure of physician smoking cessation
      interventions.
AB  - BACKGROUND: Decreasing the prevalence of smoking is an important health care
      goal, and there is evidence that physicians' advice to quit is an important
      motivator for patients. However, fewer than half of smokers report that they have
      ever been advised to quit. This study was conducted to develop a decisional
      balance measure for physician delivery of smoking cessation interventions.
      METHODS: This study included a convenience sample of 155 primary care physicians.
      A decisional balance measure was developed using item generation and development,
      pilot testing, and principal components analyses. Validity was established by
      relating the decisional balance measure to a previously validated item of
      counseling behavior and to physician stage of readiness to deliver smoking
      cessation counseling. RESULTS: Based on principal components analyses and item
      analyses, the final measure consisted of 10 Pro and 10 Con items with coefficient
      alpha of 0.83 and 0.86. The Pros and Cons scales were significantly associated
      with self-reported counseling to patients who smoke and to stage of readiness to
      deliver smoking cessation counseling. CONCLUSIONS: A decisional balance measure
      of physician smoking cessation interventions can be used to assist investigators
      in developing effective interventions to enhance the delivery of smoking
      cessation interventions in primary care settings.

PMID- 11570830
TI  - Prevalence and associated factors of cancer screening: why are so many older
      Mexican American women never screened?
AB  - OBJECTIVES: The aim of this study was to identify patterns of mammogram and
      Papanicolaou (Pap) screenings among Mexican American women ages 67 and over.
      METHODS: Data on 1,403 Mexican American women from the Hispanic Established
      Population for the Epidemiological Study of the Elderly, a cohort study of
      community-dwelling Mexican Americans ages 65 years or over from the southwestern
      United States, were analyzed. RESULTS: Mexican American women age 75 or older
      were less likely to ever have had breast or cervical screening than women ages 67
      to 74, even controlling for sociodemographic, cultural, and selected health
      factors. Overall, fewer medical conditions and never having had a hysterectomy
      were found to be associated with a decreased chance of ever having had a
      mammogram or a Pap test. Women who lacked insurance coverage and had fewer doctor
      visits were less likely to ever have had a mammogram, whereas women with low
      education, low acculturation, and lower cognitive status scores were less likely
      to ever have had a Pap test. CONCLUSIONS: If these results withstand more
      detailed studies (e.g., with the addition of important variables such as
      awareness), better communication with health professional doctors and improvement
      of access to heath care services should increase rates of both mammogram and Pap
      screenings.

PMID- 11570831
TI  - Correlates and predictors of adiposity among Mohawk children.
AB  - BACKGROUND: High rates of Type 2 diabetes in Native populations underlie the need
      for research on risk factors, including physical activity (PA) and obesity.
      METHODS: In 1994 and in 1996, 103 girls and 95 boys [mean age (standard
      deviation): 7.5 (1.3) years] attending elementary schools in two Mohawk
      communities completed a questionnaire assessing demographic and lifestyle
      variables. In addition, height, weight, and subscapular skinfold thickness (SSF)
      were measured and children performed a run/walk fitness (R/W) test. Gender
      specific multiple linear regression assessed the impact of baseline variables on
      the log of SSF at baseline and follow-up. RESULTS: In cross-sectional analyses
      among boys and girls, the common correlates of baseline SSF included failing to
      achieve the minimal fitness standard for the R/W test and being involved in
      summer sports. Additional correlates identified only among girls included
      excessive television watching, lower PA, and involvement in community sports.
      Longitudinal predictors among girls were younger age, being from the comparison
      community, excessive TV, and PA. Among boys, only baseline SSF predicted follow
      up SSF. Girls who watched excessive TV had SSFs 30 and 14% greater than those who
      watched less TV at baseline and follow-up, respectively. CONCLUSION: TV viewing
      was the only consistent determinant of adiposity among girls.

PMID- 11570832
TI  - Household educational level as a determinant of consumption of raw vegetables
      among male and female adolescents.
AB  - BACKGROUND: This study aimed to examine the association between household
      educational level and consumption of raw vegetables among adolescents and to
      assess the influence of other determinants on the association, such as family
      factors, school achievement, health behavior, meal pattern, and weight-related
      factors. A further aim was to investigate whether the associations were the same
      for male and female adolescents. METHODS: The study is based on data from the
      School Health Promotion Survey 1997-1998. Data were collected by a classroom
      administered questionnaire, which was completed by 76,201 secondary school
      pupils. The study recorded the consumption of raw vegetables, but not the
      consumption of cooked vegetables. Multivariate logistic regressions were used in
      the analyses. RESULTS: A clear positive association between educational level of
      the household and daily consumption of raw vegetables was found among
      adolescents. The adolescent's own school achievement explained part of the
      association between household educational level and consumption of raw
      vegetables. Other factors explained the association to a small degree, with meal
      pattern and weight factors having no effect. The associations were similar for
      both genders. CONCLUSIONS: Educational level in the household is an important
      determinant of consumption of raw vegetables. A household with a high educational
      level will also presumably contain adolescents who have good school achievement,
      another strong predictor of frequent consumption of raw vegetables.

PMID- 11570833
TI  - How do residents prioritize smoking cessation for young "high-risk" women?
      Factors associated with addressing smoking cessation.
AB  - BACKGROUND: Sixty-seven percent of physicians report advising their smoking
      patients to quit. Primary care residents' priorities for preventive health for a
      young "high-risk" female are unknown. Factors related to residents addressing
      smoking also need examining. METHODS: One hundred residents completed a survey
      about preventive health issues for a woman in her 20s "who leads a high-risk
      lifestyle." Residents indicated which topics they would address, and the
      likelihood that they would address each of 12 relevant preventive health topics,
      their outcome expectancies that the patient would follow their advice on each
      topic, their confidence that they could address the topic, and perceived barriers
      for addressing the topic. RESULTS: Residents listed STD prevention most
      frequently. Drug use and smoking cessation were second and third most frequently
      listed. Residents who believed that the patient would follow their advice were
      more likely to list smoking cessation than residents who had lower outcome
      expectancies for that patient. Higher barriers were negatively related to
      addressing smoking cessation. CONCLUSIONS: When time is not a barrier, residents
      are likely to address smoking cessation. Teaching residents how to incorporate
      this subject into their clinical practice is needed. Raising residents' outcome
      expectancies may increase their likelihood of addressing smoking cessation.

PMID- 11570834
TI  - Assessment of coronary risk in general practice in relation to the use of
      guidelines: a survey in Denmark.
AB  - BACKGROUND: There is a considerable gap between recommended and actually
      conducted preventive cardiology in general practice. The effect of guidelines is
      not fully evaluated. METHODS: A questionnaire containing 10 questions on
      preventive cardiology, including the use of clinical guidelines, together with
      four case stories for cardiovascular risk estimation was mailed to 205 general
      practitioners (GPs). RESULTS: Response rate was 81%. Twenty-five percent of the
      GPs had consultations in preventive cardiology at least once a day and 60% of the
      GPs thought lifestyle intervention had significant effect on cardiovascular risk.
      Approximately two-thirds of the GPs were regular users of national guidelines on
      prevention of cardiovascular disease. While the majority of GPs correctly
      assigned a patient with multiple risk factors to the high-risk category there was
      a much larger variation in risk estimations if fewer risk factors were present.
      GPs who reported use of guidelines overestimated coronary risk twice as
      frequently as nonusers of guidelines. CONCLUSION: Preventive cardiology in
      general practice is common and the effect of lifestyle intervention is well
      accepted. Poor discrimination between high- and low-risk patients may, however,
      lead to suboptimal preventive care. The use of guidelines does not seem to
      improve risk estimation and further dissemination of better tools for risk
      estimation is needed.

PMID- 11570835
TI  - Predictors of sunburn among Canadian adults.
AB  - BACKGROUND: Data from the 1996 National Survey on Sun Exposure & Protective
      Behaviors (4,023 respondents) were analyzed to identify independent predictors of
      sunburn among adult Canadians. METHODS: Multivariate models predicting sunburn
      odds were developed using unconditional logistic regression. Backward elimination
      model selection was used to identify independent predictors of sunburn. RESULTS:
      Nonbehavioral characteristics found to predict sunburn were younger age, male
      sex, light skin color, nonblack hair color, and birthplace in North America or
      Europe. Behavioral predictors of sunburn included high awareness of the UV Index,
      working outdoors in the summer, longer leisure time in the sun, forgetfulness
      about protecting oneself from the sun, and seeking a tan. Sun avoidance between
      11 AM and 4 PM was associated with lower odds of sunburn, while seeking shade
      when outside and use of protective clothing showed nonsignificant associations
      with lower sunburn odds. Sunscreen use was found to have a nonsignificant
      positive association with sunburn. CONCLUSIONS: These findings highlight risk
      factors to be considered in the targeting of sunburn reduction strategies to high
      risk groups and suggest that sun avoidance, seeking shade, and use of protective
      clothing may be effective in preventing sunburn.

PMID- 11570836
TI  - The change-in-stage and updated smoking status results from a cluster-randomized
      trial of smoking prevention and cessation using the transtheoretical model among
      British adolescents.
AB  - BACKGROUND: The transtheoretical model (TTM) and computer technology are
      promising technologies for changing health behavior, but there is little evidence
      of their effectiveness among adolescents. METHOD: Four thousand two hundred
      twenty-seven Year 9 (ages 13-14) pupils in 26 schools were randomly allocated to
      control and 4,125 in 26 schools were allocated to TTM intervention. TTM pupils
      received three whole class lessons and three sessions with an interactive
      computer program. Control pupils received no special intervention. Positive
      change in stage and smoking status was assessed from a questionnaire completed at
      baseline, 1 year, and 2 years. Random effects logistic regression was used to
      compare the change in stage and smoking status between the arms. RESULTS: Eighty
      nine percent of the TTM group and 89.3% of the control group were present at 1
      year and 86.0 and 83.1%, respectively, were present at 2-year follow-up. The
      adjusted odds ratio (95% confidence interval) for positive stage movement in the
      TTM relative to control was 1.13 (0.91-1.41) at 1 year and 1.25 (0.95-1.64) at 2
      years and for regular smoking was 1.14 (0.93-1.39) at 1 year and 1.06 (0.86-1.31)
      at 2 years. Subgroup analysis by initial smoking status revealed no benefit for
      prevention or cessation. CONCLUSIONS: The intervention was ineffective.

PMID- 11570837
TI  - A randomized controlled trial comparing three invitation strategies in a breast
      cancer screening program.
AB  - BACKGROUND: The objective of this study was to compare the response received by a
      population-based breast cancer screening program, according to three different
      invitation strategies: letters sent by mail from the program (program group),
      letters sent by mail from the Primary Health Care Team (PHT group), and direct
      contact through a trained professional (direct contact group). METHODS: We used a
      cluster-randomized controlled trial with assignment to invitation group using
      home address. Nine hundred eighty-six women of Barcelona (Spain), ages 50 to 64
      years, were invited to participate in the program. The main outcome used was the
      response rate after the first invitation. RESULTS: Five hundred sixty-four women
      accepted the invitation (57.2%). The highest response rate was achieved in the
      direct contact group (63.5%), followed by the PHT group (55.6%), the program
      group being the one that attained the lowest response rate (52.1%). The direct
      contact group had a higher probability of participating than the PHT group (RR =
      1.14, P = 0.037) or the program group (RR = 1.22, P = 0.003). The response rate
      in the direct contact group was 72.1% when the letter was received by the subject
      herself. The increase in response occurred particularly among women of lower
      educational level. CONCLUSIONS: Inviting women to participate in a breast cancer
      screening program through direct contact by trained personnel increased
      participation rate compared with mailed-letter methods. The positive effect
      appeared restricted to women with lower educational levels.

PMID- 11570838
TI  - Mediation in a family-directed program for prevention of adolescent tobacco and
      alcohol use.
AB  - BACKGROUND: Family Matters is a universal intervention designed to prevent
      adolescent tobacco and alcohol use through involvement of family members and by
      targeting family risk factors for tobacco and alcohol use. Previously reported
      findings suggest that the program reduced the prevalence of both adolescent
      smoking and drinking in the 12 months after program completion. This paper
      reports analyses conducted to identify the mediators through which the program
      influenced adolescent smoking and drinking. METHODS: One thousand fourteen
      adolescents ages 12 to 14 years and their families, identified by random-digit
      dialing, were entered into a randomized trial. Adolescents and their parents
      provided data by telephone for measuring mediator and behavioral variables at
      baseline, 3 months, and 12 months after program completion. Repeated-measures
      logistic regression with generalized estimating equations was used to assess
      mediation processes. RESULTS: The program resulted in statistically significant
      changes in several substance-specific aspects of the family, such as rule setting
      about tobacco and alcohol use. However, the intermediate family effects did not
      account for the program effects on adolescent behavior. CONCLUSIONS: The
      variables hypothesized to explain program effects were not identified by direct
      empirical examination.

PMID- 11570839
TI  - Functionally active VEGF fusion proteins.
AB  - Angiogenesis is stimulated by vascular endothelial growth factor (VEGF) acting
      via endothelial cell-specific receptors, such as VEGFR-2, that are overexpressed
      at the sites of angiogenesis. If VEGF retains activity as a fusion protein with a
      large N-terminal extension, it would facilitate development of VEGF-based
      vehicles for receptor-mediated delivery of therapeutic and diagnostic agents to
      the sites of angiogenesis. We have constructed, expressed in Escherichia coli,
      and purified VEGF fusion proteins containing a 158-amino acid N-terminal
      extension fused to human VEGF(121), VEGF(165), and VEGF(189). We report here that
      VEGF fusion proteins induce tyrosine autophosphorylation of VEGFR-2 and its
      downstream targets, as well as cell contraction in cells overexpressing VEGFR-2.
      Although N-terminal extensions decrease the affinity of VEGF fusion proteins to
      VEGFR-2, at saturating concentrations these proteins are as efficient as correct
      size VEGF(165). We hypothesize that VEGF fusion proteins may be employed for
      targeting endothelial cells at the sites of angiogenesis.

PMID- 11570840
TI  - A method for expression and purification of soluble, active Hsp47, a collagen
      specific molecular chaperone.
AB  - Hsp47 is regarded as a collagen-specific chaperone with several suggested roles
      in collagen biosynthesis under normal and disease conditions. We describe here a
      procedure for the expression and purification of Hsp47 in Escherichia coli using
      the IMPACT expression system (New England Biolabs) where the guest gene is fused
      to the adduct, intein, with a chitin-binding domain. Use of this system resulted
      in relatively high levels of soluble Hsp47 compared to other available protocols,
      especially when the bacterial cells were induced at 14 degrees C instead of 37
      degrees C. The cell lysate was passed through a chitin-Sepharose affinity column
      and Hsp47 was cleaved from intein using beta-mercaptoethanol. Minor degradation
      products were subsequently removed using a hydroxylapatite column to yield
      milligram amounts of pure and active protein suitable for structural studies. Gel
      electrophoretic analysis of the purified protein indicated the presence of a
      small proportion of trimeric species when non-reducing conditions were used. The
      ability to form a trimer may be important for its role as a chaperone. The IMPACT
      system allows for radiolabelling of purified Hsp47 with (35)S for use in binding
      experiments. Illustrative data on collagen binding by (35)S-Hsp47 are shown.

PMID- 11570841
TI  - Expression and complement d activity of porcine adipsin.
AB  - To learn how signals from adipocytes might be involved in regulation of energy
      intake and storage, we have begun to characterize the porcine complement protein,
      adipsin. Adipsin was originally identified as a protein that is produced rather
      specifically by adipocytes, is secreted, and is nearly absent in several obese
      rodent models. We now report that porcine adipsin mRNA sequence is 74% identical
      to rat and predicts a protein that has 82 and 68% identity to human and rat
      forms, respectively. Porcine adipsin has none of the asparagine glycosylation
      consensus sites which make recombinant expression of mouse adipsin in Escherichia
      coli impractical. We present a method for engineering the porcine cDNA to
      facilitate expression by E. coli and provide a protocol for refolding and
      purifying porcine adipsin protein and for immunoassay. We have found that in
      addition to adipose tissue, adipsin mRNA is present in gut tissues. Coupled with
      the fact that adipsin is required for processing of complement C3a-desArg, and
      that C3a-desArg is a potent stimulant of fatty acid acylation in adipocytes, the
      production of adipsin in the gut may be related to a mechanism for adipocyte
      removal of lipid from chylomicrons.

PMID- 11570842
TI  - Formation of soluble inclusion bodies by hpv e6 oncoprotein fused to maltose
      binding protein.
AB  - Many polypeptides overexpressed in bacteria are produced misfolded and accumulate
      as solid structures called inclusion bodies. Inclusion-body-prone proteins have
      often been reported to escape precipitation when fused to maltose-binding protein
      (MBP). Here, we have examined the case of HPV 16 oncoprotein E6. The unfused
      sequence of E6 is overexpressed as inclusion bodies in bacteria. By contrast,
      fusions of E6 to the C-terminus of MBP are produced soluble. We have analyzed
      preparations of soluble MBP-E6 fusions by using three independent approaches:
      dynamic light scattering, lateral turbidimetry, and sandwich ELISA. All three
      methods showed that MBP-E6 preparations contain highly aggregated material. The
      behavior of these soluble aggregates under denaturating conditions suggests that
      they are formed by agglomeration of misfolded E6 moieties. However, precipitation
      is prevented by the presence of the folded and highly soluble MBP moieties, which
      maintain the aggregates in solution. Therefore, the fact that a protein or
      protein domain is produced soluble when fused to the C-terminus of a carrier
      protein does not guarantee that the protein of interest is properly folded and
      active. We suggest that aggregation of fusion proteins should be systematically
      assayed, especially when these fusions are to be used for binding measurements or
      activity tests.

PMID- 11570843
TI  - High-level expression and purification of immunogenic recombinant SAG1 (P30) of
      Toxoplasma gondii in Escherichia coli.
AB  - Surface antigen 1 (SAG1) of Toxoplasma gondii is a good candidate for diagnosis
      and vaccine development, but recombinant SAG1 produced in Escheichia coli often
      loses its specific immunogenicity due to the incorrect folding. In the present
      study, a truncated SAG1 was highly expressed in E. coli as a fusion protein,
      about 30% of the total protein of the cell lysate. After a simple purification
      and refolding procedure, purified rSAG1 can be recognized by human Toxoplasma
      infective serum, and ELISA kits constructed by rSAG1 can sensitively and
      specifically detect toxoplasma infection.

PMID- 11570844
TI  - A large-scale purification of recombinant histone H1.5 from Escherichia coli.
AB  - An Escherichia coli expression system has been constructed for production of
      biologically active recombinant histone H1.5. A process of fermentation and
      purification method at a large scale has been developed. Recombinant histone H1.5
      was released from the high density cultured cells by high-pressure
      homogenization. For an efficient removal of cell debris and partial purification
      of basic histone H1.5 in a single step, the whole cell lysates were directly
      loaded onto an expanded bed column packed with the strong cation exchanger
      (Streamline SP). Complete removal of various impurities was achieved by a
      combination of hydroxyapatite chromatography and the following cation exchange
      chromatography with high grade strong cation exchanger (POROS 20 HS), and finally
      endotoxins were removed by ultrafiltration using a 100-kDa cut-off membrane,
      which gave the level of endotoxin below 0.5 EU/mg. The molecular mass of the
      recombinant histone H1.5 analyzed by MALDI-TOF-MS, and the N-terminal amino acid
      sequences were in good agreement with the authentic histone H1.5. The whole
      process gave highly purified recombinant histone H1.5 at a high yield, compared
      to the conventional process.

PMID- 11570845
TI  - Baculoviral expression and characterization of rodent cathepsin S.
AB  - The cysteinyl proteinase cathepsin S is implicated as a key enzyme in the
      processing of major histocompatability complex (MHC) class II molecules expressed
      on antigen presenting cells and thus is a potential therapeutic target for
      modulation in immune system-based disease. We have identified a form of rat
      cathepsin S, similar to a published mouse form with an eight-amino acid extended
      presequence relative to the human enzyme and the previously published rat enzyme.
      In addition, we have expressed these mouse and rat proteins in baculovirally
      infected Sf9 insect cells along with "humanized" forms truncated by eight
      residues at the amino-terminus. All forms of the rodent proteinases were
      overexpressed and milligram per litre amounts of functional enzyme could be
      isolated from the cells and/or the cell culture supernatant. Furthermore,
      addition of a carboxy-terminal hexahistidine purification tag had no effect on
      the kinetic characteristics of any of the enzyme forms against the Boc-Val-Leu
      Lys-AMC peptide substrate (rat k(cat) s(-1) approximately 30; mouse k(cat) s(-1)
      approximately 65). Differences were seen in the potency of the generic cysteine
      proteinase inhibitor, E64, against the human, mouse, or rat form of the enzyme
      (13.3 x 10(4), 43.2 x 10(4), and 25 x 10(4) K(obe)/[I] M(-1) s(-1),
      respectively). Such data highlights the need for greater awareness of species
      variation in inhibitor potency. These reagents are vital for confirming inhibitor
      potency against the endogenous form of the enzyme prior to evaluation of drug
      candidates in rodent model systems.

PMID- 11570846
TI  - Expression and characterization of recombinant human antithrombin III in Pichia
      pastoris.
AB  - Antithrombin III (ATIII) is a member of the serpin superfamily and a major
      regulator of the blood coagulation cascade. To express recombinant human ATIII
      (rATIII) in the methylotrophic yeast Pichia pastoris, we constructed an rATIII
      expression plasmid which contained the ATIII cDNA encoding mature protein region
      connected with the truncated mAOX2 promoter and the SUC2 secretion signal,
      introduced it into the P. pastoris genome, and screened for a single copy
      transformant. The secretion of rATIII from the transformant reached a level of
      320 IU/L in the culture broth at 169 h. From the culture-supernatant, rATIII was
      purified to over 99% by heparin-affinity chromatography and other column
      chromatography methods. We characterized rATIII and compared it with human plasma
      derived ATIII (pATIII). The purified rATIII possessed correct N-terminal amino
      acid sequence, and its molecular weight by SDS-PAGE of 56,000 Da was slightly
      different from the 58,000 Da of pATIII. Sequence and mass spectrometry analysis
      of BrCN fragments revealed that posttranslational modifications had occurred in
      rATIII. O-linked mannosylation was found at Ser 3 and Thr 9, and in some rATIII
      molecules, modification with O-linked mannosyl-mannose had probably occurred at
      Thr 386, close to the reactive center. Although the heparin-binding affinity of
      rATIII was 10-fold higher than that of pATIII, its inhibitory activity against
      thrombin was only half. As the conformation of rATIII and pATIII by circular
      dichroism spectroscopy was similar, O-glycosylation in the reactive center loop
      was assumed to be mainly responsible for the decreased inhibitory activity.
      pATIII can inactivate thrombin through formation of a stable thrombin-ATIII
      complex, but rATIII modified with O-glycosylation in the reactive center loop may
      act as a substrate rather than an inhibitor of thrombin.

PMID- 11570847
TI  - Increased production of active human beta(2)-adrenergic/G(alphas) fusion receptor
      in Sf-9 cells using nutrient limiting conditions.
AB  - Using the baculovirus/insect-cell expression vector system, we succeeded in
      obtaining a high yield of active human beta(2)-adrenergic receptor/G(alphas)
      fusion protein. This was achieved following high cell density production under
      nutrient-limiting conditions using a very low multiplicity of infection (MOI).
      This approach was found to significantly reduce inactive protein accumulation
      that occurred when production was done using conventional high MOI procedures.
      The maximum specific and volumetric yields of active receptor using this strategy
      increased by factors of two- and sixfold, respectively. Our results suggest that
      the increase in the ratio of active/total protein produced results from
      production under nutrient limitation. Since low multiplicity of infection offers
      many advantages for large-scale applications, we suggest that this simple
      production method should be considered when optimizing expression of G-protein
      coupled receptors and other complex proteins.

PMID- 11570848
TI  - Comparison of classical and affinity purification techniques of Mason-Pfizer
      monkey virus capsid protein: the alteration of the product by an affinity tag.
AB  - The efficiencies of different procedures for purification of the capsid protein
      (CA) of Mason-Pfizer monkey virus are compared. Plasmids encoding both wild-type
      CA and two C-terminally modified sequences of CA suitable for affinity
      chromatography purification were prepared. CA was expressed in Escherichia coli
      (i) as a wild-type protein, (ii) C-terminally extended with a six-histidine tag
      (CA 6His), and (iii) as a protein containing a C-terminal fusion to a viral
      protease cleavage site followed by a six-histidine tag (CA 6aa6His). Electron
      microscopy was used for comparison of the resulting proteins, as CA is a
      structural protein with no enzymatic activity. We have found that these C
      terminal fusions dramatically influenced the properties and morphology of
      structures formed by CA protein in E. coli. The formation of amorphous aggregates
      of CA was abolished and CA 6His and CA 6aa6His proteins formed organized
      structures. CA and CA 6aa6His accumulated in bacteria in inclusion bodies as
      insoluble proteins, CA 6His was found in a soluble form. Both six-histidine
      tagged proteins were purified using affinity chromatography under either native
      (CA 6His) or denaturing (CA 6aa6His) conditions. CA protein was purified under
      denaturing conditions using gel-filtration chromatography followed by refolding.
      All proteins were obtained at a purity >98%. Both aforementioned C-terminal
      extensions led to dramatic changes in behavior of the products and they also
      affected the tendency to form organized structures within E. coli. We show here
      that the widely used histidine anchor may significantly alter the properties of
      the protein of interest.

PMID- 11570849
TI  - Expression and purification of Dengue virus type 2 envelope protein as a fusion
      with hepatitis B surface antigen in Pichia pastoris.
AB  - The methylotrophic yeast, Pichia pastoris, has been used as a host to express the
      envelope protein (Den2E) of dengue type 2 virus (NGC strain) as a chimera with
      hepatitis B surface antigen (HBsAg): a protein known to self assemble into virus
      like particles (VLPs) and to be efficiently expressed in P. pastoris. The Den2E
      gene used in this study is a truncated version encoding the first 395 amino acid
      (aa) residues of the mature Den2E protein; the HBsAg gene encodes the full length
      226 aa HBsAg protein. Two in-frame gene fusions were constructed for
      intracellular expression in P. pastoris. The first one contains the HBsAg gene as
      the 5' partner and the Den2E gene as the 3'partner (HBsAg-Den2E). In the second
      one, the relative positions of the two partners of the gene fusion were reversed
      to create the hybrid Den2E-HBsAg gene. These fusion genes were integrated into
      the genome of P. pastoris under the control of the methanol-inducible alcohol
      oxidase (AOX1) promoter. Of the two fusions, the Den2E-HBsAg gene was expressed
      at higher levels in P. pastoris based on Northern analysis. The hybrid protein (
      approximately 68 kDa) expressed by this clone was purified to near homogeneity
      using a combination of acid precipitation, hydrophobic interaction, and
      immunoaffinity chromatographic steps. Final purification achieved was
      approximately 1400-fold with a yield of approximately 26%. The chimeric protein
      was found to possess the ability to assemble into high molecular weight
      aggregates (akin to HBsAg particles). The recombinant fusion protein eluted close
      to the void volume of a Sepharose CL-4B column indicating its macromolecular
      nature. On a CsCl density gradient the recombinant fusion protein sedimented to a
      position very similar to that of HBsAg VLPs. The hybrid protein is recognized by
      the two neutralizing monoclonals against the two components of the chimeric
      protein.

PMID- 11570850
TI  - Overexpression, purification, and characterization of a thermostable chitinase
      (Chi40) from Streptomyces thermoviolaceus OPC-520.
AB  - A new procedure for the large-scale purification of the recombinant thermostable
      chitinase (Chi40) cloned from Streptomyces thermoviolaceus in various expression
      vectors in Escherichia coli is described. Chi40 was overproduced in the cytosolic
      and secreted forms. The cytosolic form (Chi40c) was highly overproduced and
      purified by metal-affinity and ion-exchange chromatography in large amounts. The
      protein was highly active and thermostable but not homogeneous, since a
      considerable proportion of the Chi40c protein was not correctly folded as
      determined by native polyacrylamide gel electrophoresis. The Chi40 protein
      secreted into the culture medium (Chi40s) was purified by hydrophobic interaction
      and ion-exchange chromatography and high amounts of correctly folded and active
      Chi40 protein could be recovered in a short time. The enzymatic activity of
      Chi40s on a synthetic and on its natural substrate, chitin, was studied.
      Thermostability measurements showed that Chi40 has a T(m) of 60.7 degrees C at
      neutral pH. (13)C-(15)N double-labeled recombinant Chi40s was also produced and
      purified from the pECHChi40-9 construct introduced into BL21trxB(DE3) cells grown
      in minimal medium in the presence of the paramagnetic elements [(13)C]glucose and
      (15)NH(4)Cl. The presented data open the possibility of an extensive structural
      study on Chi40s by X-ray crystallography and on enzyme-substrate interaction by
      NMR spectroscopy.

PMID- 11570851
TI  - Expression and characterization of rat soluble catechol-O-methyltransferase
      fusion protein.
AB  - Rat soluble catechol-O-methyltransferase cDNA was cloned into the pCAL-n-FLAG
      vector and expressed in Escherichia coli as a fusion protein with a calmodulin
      binding peptide tag. The recombinant protein, comprising up to 30% of the total
      protein in the soluble fraction of E. coli, was purified by calmodulin affinity
      chromatography and gel filtration. Up to 16 mg of pure recombinant enzyme was
      recovered per liter of culture. Recombinant catechol-O-methyltransferase, in the
      bacterial soluble fraction, exhibited the same affinity for adrenaline as rat
      liver soluble catechol-O-methyltransferase (K(m) 428 [246, 609] microM and 531
      [330, 732] microM, respectively), as well as the same affinity for the methyl
      donor, S-adenosyl-l-methionine (K(m) 27 [9, 45] microM and 38 [21, 55] microM,
      respectively). In addition, both the recombinant and the liver enzymes displayed
      the same sensitivity to the inhibitor 3,5-dinitrocatechol (IC(50) 132 [44, 397]
      nM and 74 [38, 143] nM, respectively), and both had the same catalytic number,
      respectively, 10.1 +/- 1.5 min(-1) and 8.3 +/- 0.3 min(-1). The purified
      recombinant enzyme also displayed the same affinity for the substrate as the
      purified rat liver catechol-O-methyltransferase (K(m) 336 [75, 597] microM and
      439 [168, 711] microM, respectively) as well as the same inhibitor sensitivity
      (IC(50) 44 [19, 101] nM and 61 [33, 111] nM, respectively). This recombinant form
      of catechol-O-methyltransferase is kinetically identical to the rat liver enzyme.
      This system provides an easy and quick way of obtaining large amounts of soluble
      catechol-O-methyltransferase for both pharmacological and structural studies.

PMID- 11570852
TI  - High-level production of recombinant chicken interferon-gamma by Brevibacillus
      choshinensis.
AB  - Cytokines, such as interferon-gamma have been shown to have adjuvant and growth
      promoting activity in poultry and livestock and have the potential to be used as
      alternatives to antibiotics. We have developed an efficient system for commercial
      scale synthesis of recombinant chicken interferon-gamma (ChIFN-gamma) using
      Brevibacillus choshinensis as the host for protein production. The ChIFN-gamma
      expression vector, pNCIFN, was constructed using the novel Escherichia coli-B.
      choshinensis shuttle vector, pNCMO2. ChIFN-gamma expression was optimized by
      investigating different culture conditions and different host B. choshinensis
      mutants. The highest level of production was observed using the B. choshinensis
      HPD31-MB2 strain grown at 30 degrees C, where ChIFN-gamma was produced at
      approximately 300-500 mg/L. ChIFN-gamma was also produced as a His-tagged fusion
      protein by using the pNCHis-IFN expression vector, a derivative of pNCMO2. The
      protein was constitutively secreted into the culture supernatant and could be
      partially purified in a single step using a Ni-nitrilotriacetic acid column. This
      recombinant His-ChIFN-gamma was shown to have the same biological activity as
      native ChIFN-gamma.

PMID- 11570853
TI  - Overexpression, refolding, and purification of the histidine-tagged outer
      membrane efflux protein OprM of Pseudomonas aeruginosa.
AB  - This paper describes the overproduction and purification of the C-terminus
      polyhistidine-tagged outer membrane protein OprM, which is a part of the MexA
      MexB-OprM active efflux system of Pseudomonas aeruginosa. Renaturation of the
      protein from inclusion bodies of Escherichia coli was achieved using guanidine
      HCl as denaturing agent and n-octylpolyoxyethylene (C8POE) and n
      octyltetraoxyethylene (C8E4) as nonionic detergents. The refolded protein was
      purified by ion-exchange and nickel-affinity chromatography. The final yield was
      6 mg of pure histidine-tagged OprM per liter of E. coli culture. Renaturation was
      monitored by the effects of heating prior to SDS-PAGE, using a typical and
      exclusive property of outer membrane proteins. Immunoblotting revealed that the
      recombinant protein is addressed to the outer membrane of E. coli, after
      maturation by excision of its N-terminal signal sequence. Complementation of an
      oprM deletion mutant with the plasmid encoded histidine-tagged OprM protein
      restored antibiotic susceptibilities to wild-type levels, demonstrating
      functionality of recombinant OprM.

PMID- 11570854
TI  - High-level expression and one-step purification of cyclic amidohydrolase family
      enzymes.
AB  - The cyclic amidohydrolase family enzymes, including hydantoinase,
      dihydropyrimidinase, allantoinase and dihydroorotase, are metal-dependent
      hydrolases and play a crucial role in the metabolism of purine and pyrimidine in
      prokaryotic and eukaryotic cells. With the increasing demand for the elucidation
      of enzyme structures and functions, along with industrial applications, the
      research on the family enzymes has recently been proliferating, but the related
      enzymes had been purified conventionally by multistep purification procedures.
      Here, we reported the expression in Escherichia coli cells of maltose-binding
      protein-fused family enzymes and their one-step purification. The expression
      levels of the fusion proteins account for 20-35% of the total protein in E. coli,
      allowing approximately 2-3 mg of the purified proteins by affinity chromatography
      to be obtained per 0.3 L of bacterial culture. As more promising results, their
      nascent biochemical properties, after the cleavage of the fusion proteins with
      Factor Xa, in terms of oligomeric structure, optimal pH, specific activity, and
      kinetic property, were also conserved as those from the native enzymes. The
      availability of the family enzymes to fusion strategy shows potential as a
      convenient procedure to recombinant protein purification and accelerates the
      structure-function study of the related family enzymes.

PMID- 11570855
TI  - Purification and characterization of the Sin Nombre virus nucleocapsid protein
      expressed in Escherichia coli.
AB  - Sin Nombre virus is a member of the Hantavirus genus, family Bunyaviridae, and is
      an etiologic agent of hantavirus pulmonary syndrome. The hantavirus nucleocapsid
      (N) protein plays an important role in the encapsidation and assembly of the
      viral negative-sense genomic RNA. The Sin Nombre N protein was expressed as a C
      terminal hexahistidine fusion in Escherichia coli and initially purified by
      nickel-affinity chromatography. We developed methods to extract the soluble
      fraction and to solubilize the remainder of the N protein using denaturants.
      Maximal expression of protein from native purification was observed after a 1.5-h
      induction with IPTG (2.4 mg/L). The zwitterionic detergent Chaps did not enhance
      the yield of native purifications, but increased the yield of protein obtained
      from insoluble purifications. Both soluble and insoluble materials, purified by
      nickel-affinity chromatography, were also subjected to Hi Trap SP Sepharose fast
      flow (FF) chromatography. Both soluble and insoluble proteins had a similar
      A(280) profile on the Sepharose FF column, and both suggested the presence of a
      nucleic acid contaminant. The apparent dissociation constant of the N protein,
      purified by nickel-affinity and SP Sepharose FF chromatography, and the 5' end of
      the viral S-segment genome were measured using a filter binding assay. The N
      protein-vRNA complex had an apparent dissociation constant of 140 nM.

PMID- 11570856
TI  - Expression, purification, and characterization of recombinant nonglycosylated
      human serum transferrin containing a C-terminal hexahistidine tag.
AB  - Attachment of a hexa-His tag is a common strategy in recombinant protein
      production. The use of such a tag greatly simplifies the purification of the
      protein from the complex mixture of other proteins in the media or cell extract.
      We describe the production of two recombinant nonglycosylated human serum
      transferrins (hTF-NG), containing a factor Xa cleavage site and a hexa-His tag at
      their carboxyl-terminal ends. One of the constructs comprises the entire coding
      region for hTF (residues 1-679), while the other lacks the final three carboxyl
      terminal amino acids. After insertion of the His-tagged hTFs into the pNUT
      vector, transfection into baby hamster kidney (BHK) cells, and selection with
      methotrexate, the secreted recombinant proteins were isolated from the tissue
      culture medium. Average maximum expression levels of the His-tagged hTFs were
      about 40 mg/L compared to an average maximum of 50 mg/L for hTF-NG. The first
      step of purification involved an anion exchange column. The second step utilized
      a Poros metal chelate column preloaded with copper from which the His-tagged
      sample was eluted with a linear imidazole gradient. The His-tagged hTFs were
      characterized and compared to both recombinant hTF-NG and glycosylated hTF from
      human serum. The identity of each of the His-tagged hTFs constructs was verified
      by electrospray mass spectroscopy. In summary, the His-tagged hTF constructs
      simplify the purification of these metal-binding proteins with minimal effects on
      many of their physical properties. The His-tagged hTFs share many features common
      to hTF, including reversible iron binding, reactivity with a monoclonal antibody,
      and presence as a monomer in solution.

PMID- 11570857
TI  - Purification and characterization of a beta-lactamase from Haemophilus ducreyi in
      Escherichia coli.
AB  - A pCb plasmid encoding a beta-lactamase from Haemophilus ducreyi was transferred
      to Escherichia coli, purified, and characterized. The beta-lactamase could be
      isolated from a culture filtrate and further purified by ammonium sulfate and
      chelating Sepharose fast flow loaded with Zn(2+). The purified enzyme resulted in
      a major band at approximately 30-kDa on SDS-PAGE and its pI was determined to be
      5.4. The beta-lactamase could hydrolyze both penicillin antibiotics including
      ampicillin, benzylpenicillin, and carbenicillin as well as cephalosporin
      antibiotics including nitrocefin, cephalothin, cephaloridine, and cefoperazone.
      However, benzylpenicillin was the best substrate. The enzyme activity was
      inhibited by clavulanic acid but not by boric acid, cefotaxime,
      ethylenediaminetetraacetic acid, or phenylmethylsulfonyl fluoride. The sequence
      of the beta-lactamase gene was also determined. It confirmed that the enzyme
      belonged to a class A beta-lactamase which had 99% identity to the ampicillin
      resistance transposon Tn3 of pBR322. Two nucleotides were different between the
      E. coli (Tn3) and H. ducreyi (pCb) genes that affected the amino-acid sequence.
      The valine at position 82 (ABL 84) was changed to isoleucine and the alanine at
      position 182 (ABL 184) was changed to valine. Genetic homogeneity among beta
      lactamases is remarkable. Amino acid sequencing of some beta-lactamases has shown
      that substitution of only a few amino acids in the bla gene leads to high-level
      resistance against specific cephalosporins.

PMID- 11570858
TI  - Purification and characterization of a major secretory cellobiase, Cba2, from
      Cellulomonas biazotea.
AB  - A novel cellobiase (Cba2) was purified from the culture supernatant of
      Cellulomonas biazotea and characterized. Cba2 appeared to be a major secretory
      cellobiase in C. biazotea as its enzymatic activity was estimated to represent
      over 40% of the total extracellular beta-glucosidase activity. The enzyme was
      purified over 260-fold subsequent to ammonium sulfate precipitation, gel
      filtration chromatography, anion-exchange chromatography, and reversed-phase high
      performance liquid chromatography. Cba2 was shown by SDS-PAGE to have a large
      molecular mass of 109 kDa, which makes it one of the largest secretory
      cellobiases characterized. Its homogeneity was confirmed by N-terminal amino acid
      sequencing. The K(m) and V(max) values were 0.025 mM and 0.0048 mM min(-1),
      respectively, for the Cba2 hydrolysis of p-nitrophenyl-beta-d-glucopyranoside,
      and 0.73 mM and 0.00033 mM min(-1), respectively, for the hydrolysis of
      cellobiose (at 37 degrees C and pH 7.0). The purified enzyme has a pH optimum of
      4.8 and the optimum temperature for activity is 70 degrees C. In view of the
      secretory nature of Cba2 and the fact that it is a major component of secretory
      cellobiases of C. biazotea, it is potentially important in the enzymatic
      degradation of cellulose, and its availability as a recombinant protein may
      facilitate the studies of its biotechnological applications.

PMID- 11570859
TI  - Isotopic double-labeling of two honeybee odorant-binding proteins secreted by the
      methylotrophic yeast Pichia pastoris.
AB  - Odorant-binding proteins (OBPs) are soluble, low-molecular-weight proteins
      secreted in the sensillum lymph surrounding the dendrites of olfactory sensilla
      from a wide range of insect species. These proteins play a role in the
      solubilization, transport and/or deactivation of pheromones and odorants. In
      order to study the relationships between the molecular structure in solution and
      their ligand-binding properties, we have (13)C/(15)N-double-labeled two divergent
      honeybee OBPs, called ASP1 and ASP2, in sufficient quantities to permit a full
      determination of the structure and dynamics using heteronuclear NMR spectroscopy.
      The recombinant labeled proteins produced by the methylotrophic yeast Pichia
      pastoris have been secreted into a buffered minimal medium using native insect
      signal peptide. Mass spectrometry and Edman sequencing showed a native-like
      processing with a labeling efficiency of secreted proteins greater than 98%.
      After dialysis, the recombinant proteins were purified to homogeneity by one-step
      reversed-phase liquid chromatography. The final yield after 4-day shake-flask
      liquid culture was approximately 60 and 100 mg/L for ASP1 and ASP2, respectively.
      The inexpensive overproduction of labeled recombinant ASP1 and ASP2 should allow
      NMR studies of the structures and ligand-binding analysis in order to understand
      the relationships between structure and biological function of these proteins.

PMID- 11570860
TI  - Large-scale fractionation of molluscan shell matrix.
AB  - The numerous proteins occluded within the molluscan shell play a key role in the
      control of the mineralization process. Although extensively studied, these
      proteins are still poorly known, mainly because they are difficult to
      fractionate. In the present paper, we present, for the first time, a simple
      combined strategy for separating successfully large amounts of molluscan shell
      proteins. Since shell proteins do not absorb at 280 nm, our approach is based on
      the "blind" separation of these proteins by a preparative denaturing
      electrophoresis. They are subsequently detected on dot-blot with polyclonal
      antibodies raised against the unfractionated soluble matrix. In the present case,
      this approach allows one to collect enough purified proteins to obtain amino-acid
      composition as well as N-terminal sequences, and to perform in vitro tests and
      glycosylation studies. Furthermore, this method permits one to raise polyclonal
      antibodies against the isolated proteins.

PMID- 11570861
TI  - High-yield purification of lung surfactant proteins sp-b and sp-c and the effects
      on surface activity.
AB  - Several protocols for purification of milligram quantities of lung surfactant
      proteins (SP)-B and SP-C were studied for separation efficiency and surface
      activity of the isolated proteins recombined with synthetic phospholipids (SPL).
      SP-B and SP-C were obtained from calf lung surfactant extract by C8
      chromatography with isocratic elution by either of three solvent systems: 7:1:0.4
      MeOH/CHCl(3)/5% 0.1 M HCl (solvent A), 7:1 MeOH/CHCl(3)+ 0.1% TFA (solvent B),
      and 7:1:0.4 MeOH/CHCl(3)/H(2)O + 0.1% TFA (solvent C). Solvents A and C yielded
      pure apoprotein in a single pass, with estimated total protein recoveries of >85
      and >90%, respectively. Solvent B was less effective in purifying SP-B and SP-C,
      had a lower recovery efficiency, and gave isolates with less surface activity.
      Mixtures of SPL plus SP-B eluted with solvents A and C adsorbed to equilibrium
      surface tensions of 21-22 mN/m and reached minimum surface tensions <1 mN/m
      during dynamic cycling. Mixtures of SPL with SP-C obtained with solvents A and C
      had equilibrium surface tensions of 26-27 mN/m and minimum dynamic values of 2-7
      mN/m. The ability to obtain milligrams of virtually lipid-free SP-B and SP-C in a
      single column pass will facilitate research on their biological, structural, and
      biophysical properties.

PMID- 11570862
TI  - Purification of a model substrate for transcription factor phosphorylation by
      ERK2.
AB  - ERK2 belongs to the mitogen-activated protein kinase subfamily, which plays a
      pivotal role in cell signal transduction, in which it mediates effects on
      proliferation and differentiation by growth factors and hormones. While its
      cellular function has been under intense scrutiny since its initial discovery
      nearly 15 years ago, little progress has been made in understanding its kinetic
      mechanism. Such an understanding is important for the development of potent and
      specific inhibitors. A contributory factor has been the lack of a protein
      substrate suitable for rigorous mechanistic studies. Here we report the
      expression, purification, and characterization of the N-terminus (residues 1
      through 138) of the transcription factor Ets-1, an excellent model substrate for
      ERK2 mechanistic studies. (His(6)-tagged)Ets-1(1-138) was expressed in
      Escherichia coli and rapidly purified in two steps by nickel-agarose-affinity
      chromatography, followed by high-resolution Mono-Q anion-exchange chromatography.
      A yield of 60 mg of the purified protein per liter of culture was obtained and
      could be stored conveniently at -80 degrees C in water. Rigorous characterization
      demonstrated that under the assay conditions, (His(6)-tagged)Ets-1(1-138) is
      exclusively phosphorylated on residue Thr-38 by ERK2 with the following Michaelis
      parameters: k(cat) = 17 s(-1), K(ATP)(m) = 140 microM, K(ATP)(i) = 68 microM,
      K(Ets-1)(m) = 19 microM, and K(Ets-1)(i) = 9.3 microM.

PMID- 11570863
TI  - A new method for the isolation of histatins 1, 3, and 5 from parotid secretion
      using zinc precipitation.
AB  - Histatins, a family of small-molecular-weight, histidine-rich cationic salivary
      proteins, have been difficult to isolate in an efficient way by conventional
      procedures due to their anomalous interactions with chromatographic resins. In
      the present study we explored the possibility of developing a new isolation
      procedure based on recent observations that histatins associate with various
      metal ions, including zinc. Since solubility studies showed that histatin 5 forms
      precipitates with zinc under alkaline conditions, we investigated whether this
      characteristic could be exploited for the preparative isolation of histatins from
      salivary secretions. A fast and efficient two-step procedure was developed using
      zinc precipitation of histatins from human parotid secretion followed by final
      purification using reversed-phase high-performance liquid chromatography (HPLC).
      Analysis of zinc precipitates by Tricine-SDS-PAGE, cationic PAGE, HPLC, and mass
      spectrometry revealed the presence of the three major histatins, 1, 3, and 5, as
      well as statherin. The histatin yield obtained by the precipitation step was
      approximately 90%. Therefore, zinc precipitation of histatins from glandular
      salivary secretions is a novel, rapid, and effective means for the isolation of
      these proteins.

PMID- 11570864
TI  - Cost-effective and uniform (13)C- and (15)N-labeling of the 24-kDa N-terminal
      domain of the Escherichia coli gyrase B by overexpression in the photoautotrophic
      cyanobacterium Anabaena sp. PCC 7120.
AB  - Structural studies of biomolecules using nuclear magnetic resonance (NMR) rely on
      the availability of samples enriched in (13)C and (15)N isotopes. While
      (13)C/(15)N-labeled proteins are generally obtained by overexpression in
      transformed Escherichia coli cells cultured in the presence of an expensive
      mixture of labeled precursors, those of the photoautotrophic cyanobacterium
      Anabaena sp. PCC 7120 can be uniformly labeled by growing them in medium
      containing Na(15)NO(3) and NaH(13)CO(3) as the sole nitrogen and carbon sources.
      We report here a novel vector-host system suitable for the efficient preparation
      of uniformly (13)C/(15)N-labeled proteins in Anabaena sp. PCC 7120. The 24-kDa N
      terminal domain of the E. coli gyrase B subunit, used as a test protein, was
      cloned into the pRL25C shuttle vector under the control of the tac promoter. The
      transformed Anabaena cells were grown in the presence of the labeled mineral
      salts and culture conditions were optimized to obtain over 90% of (13)C and (15)N
      enrichment in the constitutively expressed 24-kDa polypeptide. The yield of
      purified 24-kDa protein after dual isotope labeling under anaerobic conditions
      was similar to that obtained with E. coli cells bearing a comparable expression
      vector and cultured in parallel in a commercially available labeling medium.
      Furthermore, as probed by NMR spectroscopy and mass spectrometry, the 24-kDa N
      terminal domain expressed in Anabaena was identical to the E. coli sample,
      demonstrating that it was of sufficient quality for 3D-structure determination.
      Because the Anabaena system was far more advantageous taking into consideration
      the expense for the labels that were necessary, these results indicate that
      Anabaena sp. PCC 7120 is an economic alternative for the (13)C/(15)N-labeling of
      soluble recombinant proteins destined for structural studies.

PMID- 11570865
TI  - Aminoacyl-S-enzyme intermediates in beta-hydroxylations and alpha,beta
      desaturations of amino acids in peptide antibiotics.
AB  - Many of the alpha-amino acids found in proteins are shunted into microbial
      secondary metabolism to form peptide antibiotics by specific oxidation, including
      hydroxylation, at the beta carbon. Examples for the enzymatic hydroxylation of
      tyrosine and histidine and for desaturation of proline during covalent attachment
      as aminoacyl-S-pantetheinyl enzyme intermediates suggest a general strategy in
      peptide antibiotic biosynthesis.

PMID- 11570866
TI  - Disorder-to-order transition of the active site of human class Pi glutathione
      transferase, GST P1-1.
AB  - Glutathione transferases comprise a large family of cellular detoxification
      enzymes that function by catalyzing the conjugation of glutathione (GSH) to
      electron-deficient centers on carcinogens and other toxins. NMR methods have been
      used to characterize the structure and dynamics of a human class pi enzyme, GST
      P1-1, in solution. Resonance assignments have been obtained for the unliganded
      enzyme and the GSH and S-hexylglutathione (GS-hexyl) complexes. Differences in
      chemical shifts between the GSH and GS-hexyl complexes suggest more extensive
      structural differences between these two enzyme-ligand complexes than detected by
      previous crystallographic methods. The NMR studies reported here clearly show
      that an alpha-helix (alpha2) within the GSH binding site exists in multiple
      conformations at physiological temperatures in the absence of ligand. A single
      conformation of alpha2 is induced by the presence of either GSH or GS-hexyl or a
      reduction in temperature to below 290 K. The large enthalpy of the transition (
      approximately 150 kJ/mol) suggests a considerable structural rearrangement of the
      protein. The Gibbs free energy for the transition to the unfolded form is on the
      order of -4 to -6 kJ/mol at physiological temperatures (37 degrees C). This order
      to-disorder transition contributes substantially to the overall thermodynamics of
      ligand binding and should be considered in the design of selective inhibitors of
      class pi glutathione transferases.

PMID- 11570867
TI  - Ligand variation in the transferrin family: the crystal structure of the H249Q
      mutant of the human transferrin N-lobe as a model for iron binding in insect
      transferrins.
AB  - Proteins of the transferrin (Tf) family play a central role in iron homeostasis
      in vertebrates. In vertebrate Tfs, the four iron-binding ligands, 1 Asp, 2 Tyr,
      and 1 His, are invariant in both lobes of these bilobal proteins. In contrast,
      there are striking variations in the Tfs that have been characterized from insect
      species; in three of them, sequence changes in the C-lobe binding site render it
      nonfunctional, and in all of them the His ligand in the N-lobe site is changed to
      Gln. Surprisingly, mutagenesis of the histidine ligand, His249, to glutamine in
      the N-lobe half-molecule of human Tf (hTf/2N) shows that iron binding is
      destabilized and suggests that Gln249 does not bind to iron. We have determined
      the crystal structure of the H249Q mutant of hTf/2N and refined it at 1.85 A
      resolution (R = 0.221, R(free) = 0.246). The structure reveals that Gln249 does
      coordinate to iron, albeit with a lengthened Fe-Oepsilon1 bond of 2.34 A. In
      every other respect, the protein structure is unchanged from wild-type.
      Examination of insect Tf sequences shows that the K206.K296 dilysine pair, which
      aids iron release from the N-lobes of vertebrate Tfs, is not present in the
      insect proteins. We conclude that substitution of Gln for His does destabilize
      iron binding, but in the insect Tfs this is compensated by the loss of the
      dilysine interaction. The combination of a His ligand with the dilysine pair in
      vertebrate Tfs may have been a later evolutionary development that gives more
      sophisticated pH-mediated control of iron release from the N-lobe of
      transferrins.

PMID- 11570868
TI  - Structures of gramicidins A, B, and C incorporated into sodium dodecyl sulfate
      micelles.
AB  - Gramicidins A, B, and C are the three most abundant, naturally occurring
      analogues of this family of channel-forming antibiotic. GB and GC differ from the
      parent pentadecapeptide, GA, by single residue mutations, W11F and W11Y,
      respectively. Although these mutations occur in the cation binding region of the
      channel, they do not affect monovalent cation specificity, but are known to alter
      cation-binding affinities, thermodynamic parameters of cation binding,
      conductance and the activation energy for ion transport. The structures of all
      three analogues incorporated into deuterated sodium dodecyl sulfate micelles have
      been obtained using solution state 2D-NMR spectroscopy and molecular modeling.
      For the first time, a rigorous comparison of the 3D structures of these analogues
      reveals that the amino acid substitutions do not have a significant effect on
      backbone conformation, thus eliminating channel differences as the cause of
      variations in transport properties. Variable positions of methyl groups in valine
      and leucine residues have been linked to molecular motions and are not likely to
      affect ion flow through the channel. Thus, it is concluded that changes in the
      magnitude and orientation of the dipole moment at residue 11 are responsible for
      altering monovalent cation transport.

PMID- 11570869
TI  - Binding of correolide to the K(v)1.3 potassium channel: characterization of the
      binding domain by site-directed mutagenesis.
AB  - Correolide is a novel immunosuppressant that inhibits the voltage-gated potassium
      channel K(v)1.3 [Felix et al. (1999) Biochemistry 38, 4922-4930].
      [(3)H]Dihydrocorreolide (diTC) binds with high affinity to membranes expressing
      homotetrameric K(v)1.3 channels, and high affinity diTC binding can be conferred
      to the diTC-insensitive channel, K(v)3.2, after substitution of three
      nonconserved residues in S(5) and S(6) with the corresponding amino acids present
      in K(v)1.3 [Hanner et al. (1999) J. Biol. Chem. 274, 25237-25244]. Site-directed
      mutagenesis along S(5) and S(6) of K(v)1.3 was employed to identify those
      residues that contribute to high affinity binding of diTC. Binding of
      monoiodotyrosine-HgTX(1)A19Y/Y37F ([(125)I]HgTX(1)A19Y/Y37F) in the external
      vestibule of the channel was used to characterize each mutant for both tetrameric
      channel formation and levels of channel expression. Substitutions at Leu(346) and
      Leu(353) in S(5), and Ala(413), Val(417), Ala(421), Pro(423), and Val(424) in
      S(6), cause the most dramatic effect on diTC binding to K(v)1.3. Some of the
      critical residues in S(6) appear to be present in a region of the protein that
      alters its conformation during channel gating. Molecular modeling of the S(5)
      S(6) region of K(v)1.3 using the X-ray coordinates of the KcsA channel, and other
      experimental constraints, yield a template that can be used to dock diTC in the
      channel. DiTC appears to bind in the water-filled cavity below the selectivity
      filter to a hydrophobic pocket contributed by the side chains of specific
      residues. High affinity binding is predicted to be determined by the
      complementary shape between the bowl-shape of the cavity and the shape of the
      ligand. The conformational change that occurs in this region of the protein
      during channel gating may explain the state-dependent interaction of diTC with
      K(v)1.3.

PMID- 11570870
TI  - An unusually low pK(a) for Cys282 in the active site of human muscle creatine
      kinase.
AB  - All phosphagen kinases contain a conserved cysteine residue which has been shown
      by crystallographic studies, on both creatine kinase and arginine kinase, to be
      located in the active site. There are conflicting reports as to whether this
      cysteine is essential for catalysis. In this study we have used site-directed
      mutagenesis to replace Cys282 of human muscle creatine kinase with serine and
      methionine. In addition, we have replaced Cys282, conserved across all creatine
      kinases, with alanine. No activity was found with the C282M mutant. The C282S
      mutant showed significant, albeit greatly reduced, activity in both the forward
      (creatine phosphorylation) and reverse (MgADP phosphorylation) reactions. The
      K(m) for creatine was increased approximately 10-fold, but the K(m) for
      phosphocreatine was relatively unaffected. The V and V/K pH-profiles for the wild
      type enzyme were similar to those reported for rabbit muscle creatine kinase, the
      most widely studied creatine kinase isozyme. However, the V/K(creatine) profile
      for the C282S mutant was missing a pK of 5.4. This suggests that Cys282 exists as
      the thiolate anion, and is necessary for the optimal binding of creatine. The low
      pK of Cys282 was also determined spectrophotometrically and found to be 5.6 +/-
      0.1. The S284A mutant was found to have reduced catalytic activity, as well as a
      15-fold increase in K(m) for creatine. The pK(a) of Cys282 in this mutant was
      found to be 6.7 +/- 0.1, indicating that H-bonding to Ser284 is an important, but
      not the sole, factor contributing to the unusually low pK(a) of Cys282.

PMID- 11570871
TI  - Photoaffinity cross-linking of Alzheimer's disease amyloid fibrils reveals
      interstrand contact regions between assembled beta-amyloid peptide subunits.
AB  - The assembly of the beta-amyloid peptide (Abeta) into amyloid fibrils is
      essential to the pathogenesis of Alzheimer's disease. Detailed structural
      information about fibrillogenesis has remained elusive due to the highly
      insoluble, noncrystalline nature of the assembled peptide. X-ray fiber
      diffraction, infrared spectroscopy, and solid-state NMR studies performed on
      fibrils composed of Abeta peptides have led to conflicting models of the
      intermolecular alignment of beta-strands. We demonstrate here the use of
      photoaffinity cross-linking to determine high-resolution structural constraints
      on Abeta monomers within amyloid fibrils. A photoreactive Abeta(1-40) ligand was
      synthesized by substituting L-p-benzoylphenylalanine (Bpa) for phenylalanine at
      position 4 (Abeta(1-40) F4Bpa). This peptide was incorporated into synthetic
      amyloid fibrils and irradiated with near-UV light. SDS-PAGE of dissolved fibrils
      revealed the light-dependent formation of a covalent Abeta dimer. Enzymatic
      cleavage followed by mass spectrometric analysis demonstrated the presence of a
      dimer-specific ion at MH(+) = 1825.9, the predicted mass of a fragment composed
      of the N-terminal Abeta(1-5) F4Bpa tryptic peptide covalently attached to the C
      terminal Abeta(29-40) tryptic peptide. MS/MS experiments and further chemical
      modifications of the cross-linked dimer led to the localization of the photo
      cross-link between the ketone of the Bpa4 side chain and the delta-methyl group
      of the Met35 side chain. The Bpa4-Met35 intermolecular cross-link is consistent
      with an antiparallel alignment of Abeta peptides within amyloid fibrils.

PMID- 11570872
TI  - Gene cloning of a new plasma CC chemokine, activating and attracting myeloid
      cells in synergy with other chemoattractants.
AB  - Chemokines are important mediators of cell migration during inflammation and
      normal leukocyte trafficking. Inflammatory chemokines are induced in multiple
      cell types at sites of infection. Here, we describe a novel bovine CC chemokine,
      designated regakine-1, that is constitutively present at high concentrations in
      plasma. Cloning of its gene revealed an expected two intron/three exon
      organization, with a rather long first intron. In addition to a 21-residue signal
      peptide, the coding sequence corresponded to a 71-residue secreted protein.
      However, the natural regakine-1 protein missed the COOH-terminal lysine residue.
      Regakine-1 has only weak sequence similarity (<50% identical residues) with other
      animal or human chemokines. Northern blot analysis demonstrated regakine-1 RNA
      expression in spleen and lung. At physiological concentrations (30-100 ng/mL),
      natural 7.5 kDa regakine-1 stimulated gelatinase B release from neutrophils and
      chemoattracted immature myeloid HL-60 cells, as well as mature granulocytes.
      Regakine-1 was more potent on human myeloid cells than the human plasma CC
      chemokine hemofiltrate CC chemokine-1 (HCC-1). Moreover, regakine-1 synergized
      with the bacterial peptide N-formylmethionylleucylphenylalanine (fMLP), yielding
      a 10-fold increase in neutrophil chemotactic response above their additive
      effect. Regakine-1 did not compete with interleukin-8 (IL-8) for binding to
      neutrophils, nor did it affect fMLP-induced calcium signaling, suggesting that
      regakine-1 recognizes a different receptor. In view of its high constitutive
      plasma concentration, regakine-1 is believed to recruit myeloid cells into the
      circulation, whereas its synergy with other neutrophil chemoattractants suggests
      that it also enhances the inflammatory response to infection.

PMID- 11570873
TI  - A novel fluorescence assay to study propeptide interaction with gamma-glutamyl
      carboxylase.
AB  - The vitamin K-dependent gamma-glutamyl carboxylase catalyzes the
      posttranslational modification of select glutamate residues of its vitamin K
      dependent substrates to gamma-carboxyglutamate. In this report, we describe a new
      fluorescence assay that is sensitive and specific for the propeptide binding site
      of active carboxylase. We employed the assay to make three important
      observations: (1) A tight binding fluorescein-labeled consensus propeptide can be
      used to quantify the active fraction of the enzyme. (2) The off-rate for a
      fluorescein-labeled factor IX propeptide was 3000-fold slower than the rate of
      carboxylation, a difference that may explain how carboxylase can carry out
      multiple carboxylations of a substrate during the same binding event. (3) We show
      evidence that substrate binding to the active site modifies the propeptide
      binding site of carboxylase. The significant (9-fold) differences in off-rates
      for the propeptide in the presence and absence of its co-substrates may represent
      a release mechanism for macromolecular substrates from the enzyme. Additionally,
      sedimentation velocity and equilibrium experiments indicate a monomeric
      association of enzyme with propeptide. Furthermore, the carboxylase preparation
      is monodisperse in the buffer used for our studies.

PMID- 11570874
TI  - Modulation of recombinant human prostate-specific antigen: activation by
      Hofmeister salts and inhibition by azapeptides. Appendix: thermodynamic
      interpretation of the activation by concentrated salts.
AB  - Prostate specific antigen (PSA, also known as human kallikrein 3) is an important
      diagnostic indicator of prostatic disease. PSA exhibits low protease activity
      (>10(4)-fold less than chymotrypsin) under the usual in vitro assay conditions.
      In addition, PSA does not react readily with prototypical serine protease
      inactivators. We expressed human PSA (rh-PSA) in Escherichia coli and have
      demonstrated that rh-PSA has properties similar to those of native PSA isolated
      from human seminal fluid. Both PSA and rh-PSA are >10(3)-fold more active in the
      presence of 1.3 M Na(2)SO(4). This activation is anion-dependent, following the
      Hofmeister series when normality is considered: SO(4)(2)(-) approximately citrate
      > Ac(-) > Cl(-) > Br(-) > I(-). The nature of the cation has little effect on
      salt activation. The rate of inactivation of rh-PSA by DFP is 30-fold faster in
      the presence of 0.9 M Na(2)SO(4), and the rate of inactivation by Suc-Ala-Ala-Pro
      Phe-CK is >20-fold faster under these conditions. Azapeptides containing Phe or
      Tyr at position P(1) also inactivate rh-PSA in the presence of high salt
      concentrations. These compounds represent the first described inhibitors designed
      to utilize the substrate binding subsites of PSA. CD spectroscopy demonstrates
      that the conformation of rh-PSA changes in the presence of high salt
      concentrations. Analytical ultracentifugation and dynamic light scattering
      indicate that PSA remains monomeric under high-salt conditions. Interestingly,
      human prostatic fluid contains as much as 150 micro mol citrate/g wet weight,
      which suggests that salt concentrations may regulate PSA activity in vivo.

PMID- 11570875
TI  - Resolution of Michaelis complex, acylation, and conformational change steps in
      the reactions of the serpin, plasminogen activator inhibitor-1, with tissue
      plasminogen activator and trypsin.
AB  - Michaelis complex, acylation, and conformational change steps were resolved in
      the reactions of the serpin, plasminogen activator inhibitor-1 (PAI-1), with
      tissue plasminogen activator (tPA) and trypsin by comparing the reactions of
      active and Ser 195-inactivated enzymes with site-specific fluorescent-labeled PAI
      1 derivatives that report these events. Anhydrotrypsin or S195A tPA-induced
      fluorescence changes in P1'-Cys and P9-Cys PAI-1 variants labeled with the
      fluorophore, NBD, indicative of a substrate-like interaction of the serpin
      reactive loop with the proteinase active-site, with the P1' label but not the P9
      label perturbing the interactions by 10-60-fold. Rapid kinetic analyses of the
      labeled PAI-1-inactive enzyme interactions were consistent with a single-step
      reversible binding process involving no conformational change. Blocking of PAI-1
      reactive loop-beta-sheet A interactions through mutation of the P14 Thr --> Arg
      or annealing a reactive center loop peptide into sheet A did not weaken the
      binding of the inactive enzymes, suggesting that loop-sheet interactions were
      unlikely to be induced by the binding. Only active trypsin and tPA induced the
      characteristic fluorescence changes in the labeled PAI-1 variants previously
      shown to report acylation and reactive loop-sheet A interactions during the PAI-1
      proteinase reaction. Rapid kinetic analyses showed saturation of the reaction
      rate constant and, in the case of the P1'-labeled PAI-1 reaction, biphasic
      changes in fluorescence indicative of an intermediate resembling the noncovalent
      complex on the path to the covalent complex. Indistinguishable K(M) and k(lim)
      values of approximately 20 microM and 80-90 s(-1) for reaction of the two labeled
      PAI-1s with trypsin suggested that a diffusion-limited association of PAI-1 and
      trypsin and rate-limiting acylation step, insensitive to the effects of labeling,
      controlled covalent complex formation. By contrast, differing values of K(M) of
      1.7 and 0.1 microM and of k(lim) of 17 and 2.6 s(-1) for tPA reactions with P1'
      and P9-labeled PAI-1s, respectively, suggested that tPA-PAI-1 exosite
      interactions, sensitive to the effects of labeling, promoted a rapid association
      of PAI-1 and tPA and reversible formation of an acyl-enzyme complex but impeded a
      rate-limiting burial of the reactive loop leading to trapping of the acyl-enzyme
      complex. Together, the results suggest a kinetic pathway for formation of the
      covalent complex between PAI-1 and proteinases involving the initial formation of
      a Michaelis-type noncovalent complex without significant conformational change,
      followed by reversible acylation and irreversible reactive loop conformational
      change steps that trap the proteinase in a covalent complex.

PMID- 11570876
TI  - Structural features of the Abeta amyloid fibril elucidated by limited
      proteolysis.
AB  - Although the gross morphology of amyloid fibrils is fairly well understood, very
      little is known about how the constituent polypeptides fold within the amyloid
      folding motif. In the experiments reported here, we used trypsin and chymotrypsin
      to conduct limited proteolysis studies on synthetic amyloid fibrils composed of
      the Alzheimer's disease peptide Abeta(1-40). In both reactions, the extreme N
      terminal proteolytic fragment is released from fibrils as rapidly as it is from
      the Abeta monomer, while other proteolytic fragments are generated much more
      slowly. Furthermore, aggregated material isolated by centrifugation of
      intermediate digestion time points from both proteases contains, in addition to
      full-length material, peptides that possess mature C-termini but truncated N
      termini. These data strongly suggest that the N-terminal region of Abeta is not
      involved in the beta-sheet network of the amyloid fibril, while the C-terminus is
      essentially completely engaged in protective-presumably beta-sheet-structure. In
      both digests, release of the extreme N-terminal fragments of Abeta(1-40) reaches
      plateau values corresponding to about 80% of the total available Abeta. This
      suggests that there are two classes of peptides in the fibril: while the majority
      of Abeta molecules have an exposed N-terminus, about 20% of the peptides have an
      N-terminus that is protected from proteolysis within the fibril structure. The
      most likely cause of this heterogeneity is the lateral association of
      protofilaments into the fibril structure, which would be expected to generate a
      unique environment for those Abeta N-termini located at protofilament packing
      interfaces and/or in the interior core region between the packed protofilaments.
      This suggests that the N-terminal region of Abeta, while not directly involved in
      the beta-sheet network of the fibril, may contribute to fibril stability by
      participating in protofilament packing.

PMID- 11570877
TI  - Insulin regulation of gene expression through the forkhead transcription factor
      Foxo1 (Fkhr) requires kinases distinct from Akt.
AB  - Insulin inhibits expression of certain liver genes through the phosphoinositol
      (PI) 3-kinase/Akt pathway. However, whether Akt activity is both necessary and
      sufficient to mediate these effects remains controversial. The forkhead proteins
      (Foxo1, Foxo3, and Foxo4, previously known as Fkhr or Afx) are transcriptional
      enhancers, the activity of which is inhibited by insulin through phosphorylation
      dependent translocation and nuclear exclusion. Others and we have previously
      shown that the forkhead protein Foxo1 is phosphorylated at three different sites:
      S(253), T(24), and S(316). We have also shown that T(24) fails to be
      phosphorylated in hepatocytes lacking insulin receptors, and we have suggested
      that this residue is targeted by a kinase distinct from Akt. In this study, we
      have further analyzed the ability of Akt to phosphorylate different Foxo1 sites
      in control and insulin receptor-deficient hepatocytes. Expression of a dominant
      negative Akt (Akt-AA) in control hepatocytes led to complete inhibition of
      endogenous Akt, but failed to inhibit Foxo1 T(24) phosphorylation and,
      consequently, insulin suppression of IGFBP-1 promoter activity. Conversely,
      expression of a constitutively active Akt (Akt-Myr) in insulin receptor-deficient
      hepatocytes led to an overall increase in the level of Foxo1 phosphorylation, but
      failed to induce T(24) and S(316) phosphorylation. These data indicate that the
      Foxo1 T(24) and S(316) kinases are distinct from Akt, and suggest that the
      pathways required for insulin regulation of hepatic gene expression diverge
      downstream of PI 3-kinase.

PMID- 11570878
TI  - Translational properties of mHNA, a messenger RNA containing anhydrohexitol
      nucleotides.
AB  - Short messenger RNAs (mRNAs) with hexitol residues in two codons were constructed
      and their properties were studied in an Escherichia coli in vitro translation
      system. The replacement of the natural ribonucleotides of mRNA in the AUG start
      codon and the UUC second codon by hexitol nucleotides did not influence the main
      steps of translation, as indicated by the same level of binding of mRNA with or
      without hexitol residues under P-site conditions, and the same yield of tRNA
      binding to the P- and A-sites. Moreover, both peptide formation and translocation
      took place on mRNAs with hexitol residues. The presence of an A-type messenger
      hexitol nucleic acid (mHNA)-transfer RNA (tRNA) duplex is important for efficient
      translation and the 2'-OH function in mRNA is not necessary for binding and
      movement through the ribosome. Groove shape recognition of the codon-anticodon
      complex, more than hydrogen-bond interactions of ribose residues in mRNA, is an
      important factor for correct translation.

PMID- 11570879
TI  - Use of a combined enzymatic digestion/ESI mass spectrometry assay to study the
      effect of TATA-binding protein on photoproduct formation in a TATA box.
AB  - Recently, it was reported that TATA-binding protein (TBP) enhances (6-4)
      photoproduct formation in a TATA box under UVC irradiation [Aboussekhra and Thoma
      (1999) EMBO J. 18, 433-443]. The conclusions of that study were based on an
      indirect enzymatic assay that was not specific for (6-4) photoproducts. Herein we
      report the use of a recently developed coupled enzymatic digestion/mass
      spectrometry assay [Wang et al. (1999) Chem. Res. Toxicol. 12, 1077-1082] to
      identify unambiguously and quantify the photoproducts formed in a TATA box
      containing dodecamer duplex sequence in the presence or absence of TBP binding.
      Exposure of the adenovirus major late promoter TATA box to a high dose of UVC
      irradiation in the absence of the C-terminal domain of yeast TBP leads to
      predominant formation of the cis-syn dimer within the T(4) tract, whereas
      exposure in the presence of TBP leads to almost exclusive formation of the (6-4)
      photoproduct. In contrast, the (6-4) product is not detected at high doses of UVB
      irradiation in the absence of TBP but is detected in the presence of TBP,
      although the cis-syn product predominates. When the products of UVB irradiation
      were subsequently exposed to a high dose of UVC irradiation in the presence of
      TBP, the (6-4) photoproduct again becomes nearly the exclusive photoproduct,
      indicating that the cis-syn dimer is being reversed to TT by UVC light. Both cis
      syn and (6-4) photoproducts are formed in approximately equal amounts upon
      irradiation with small doses of UVC in the presence of TBP, but the fraction of
      (6-4) photoproduct increases with dose. Through the use of a TATA box containing
      a site-specifically deuterated thymine, it was found that (6-4) photoproducts
      formed most selectively at the second and third positions of the T(4) tract upon
      either UVB or UVC irradiation in the presence of TBP. By using the same
      substrate, it was found that UVC-induced TA formation was inhibited by TBP
      binding and that TA formation was greatest at the 5' end of the TATA sequence.

PMID- 11570880
TI  - Multiple-step kinetic mechanisms of the ssDNA recognition process by human
      polymerase beta in its different ssDNA binding modes.
AB  - The kinetics of human polymerase beta (pol beta) binding to the single-stranded
      DNA, in the (pol beta)(16) and (pol beta)(5) binding modes, that differ in the
      number of occluded nucleotide residues in the protein-DNA complexes, have been
      examined, using the fluorescence stopped-flow technique. This is the first
      determination of the mechanism of ssDNA recognition by human pol beta. Binding of
      the enzyme to the ssDNA containing fluorescein in the place of one of the
      nucleotides is characterized by a strong DNA fluorescence increase, providing the
      required signal to quantitatively examine the complex mechanism of ssDNA
      recognition. The experiments were performed with the ssDNA 20-mer, which engages
      the polymerase in the (pol beta)(16) binding mode and encompasses the total DNA
      binding site of the enzyme, and with the 10-mer, which exclusively forms the (pol
      beta)(5) binding mode engaging only the 8-kDa domain of the enzyme. The obtained
      data and analyses indicate that the (pol beta)(16) formation occurs by a minimum
      four-step, sequential mechanism: (reaction: see text). Formation of the (pol
      beta)(5) binding mode proceeds with the same mechanism; however, both binding
      modes differ in the energetics of the partial reactions and the structure of the
      intermediates. Quantitative amplitude analysis, using the matrix projection
      operator approach, allowed us to determine molar fluorescence intensities of all
      intermediates relative to the fluorescence of the free DNA. The results indicate
      that (pol beta)(16) binding mode formation, which is initiated by the association
      of the 8-kDa domain with the DNA, is followed by subsequent intermediates
      stabilized by DNA binding to the 31-kDa domain. Comparison with the (pol beta)(5)
      binding mode formation indicates that transitions of the enzyme-DNA complex in
      both modes are induced at the interface of the 8-kDa domain and the DNA. The
      sequential nature of the mechanism indicates the lack of a conformational
      preequilibrium of the enzyme prior to ssDNA binding.

PMID- 11570881
TI  - Efficiency of excision of 8-oxo-guanine within DNA clustered damage by XRS5
      nuclear extracts and purified human OGG1 protein.
AB  - A major DNA lesion is the strongly mutagenic 8-oxo-7,8-dihydroguanine (8-oxoG)
      base, formed by oxidative attack at guanine and which leads to a high level of
      G.C-->T.A transversions. Clustered DNA damages are formed in DNA following
      exposure to ionizing radiation or radiomimetic anticancer agents and are thought
      to be biologically severe. The presence of 8-oxoG within clustered DNA damage may
      present a challenge to the repair machinery of the cell, if the OGG1 DNA
      glycosylase/AP lyase protein, present in eukaryotic cells, does not efficiently
      excise its substrate, 8-oxoG. In this study, specific oligonucleotide constructs
      containing an 8-oxoG located in several positions opposite to another damage (5,6
      dihydrothymine (DHT), uracil, 8-oxoG, AP site, or various types of single strand
      breaks) were used to determine the relative efficiency of purified human OGG1 and
      mammalian XRS5 nuclear extracts to excise 8-oxoG from clustered damages. A base
      damage (DHT, uracil, and 8-oxoG) on the opposite strand has little or no
      influence on the rate of excision of 8-oxoG whereas the presence of either an AP
      site or various types of single strand breaks has a strong inhibitory effect on
      the formation of a SSB due to the excision of 8-oxoG by both hOGG1 and the
      nuclear extract. The binding of hOGG1 to 8-oxoG is not significantly affected by
      the presence of a neighboring lesion.

PMID- 11570882
TI  - Effect of temperature, pH, and metal ion binding on the secondary structure of
      bacteriorhodopsin: FT-IR study of the melting and premelting transition
      temperatures.
AB  - We have measured the temperature dependence of the FT-IR spectra of
      bacteriorhodopsin (bR) as a function of the pH and of the divalent cation
      regeneration with Ca(2+) and Mg(2+). It has been found that although the
      irreversible melting transition shows a strong dependence on the pH of the native
      bR, the premelting reversible transition at 78-80 degrees C shows very little
      variation over the pH range studied. It is further shown that the acid blue bR
      shows a red-shifted amide I spectrum at physiological temperature, which shows a
      more typical alpha-helical frequency component at 1652 cm(-)(1) and could be the
      reason for the observed reduction of its melting temperature and lack of an
      observed premelting transition. Furthermore, the thermal transitions for Ca(2+)-
      and Mg(2+)-regenerated bR (Ca-bR and Mg-bR, respectively) each show a premelting
      transition at the same 78-80 degrees C temperature as the native purple membrane,
      but the irreversible melting transition has a slight dependence on the cation
      identity. The pH dependence of the Ca(2+)-regenerated bR is studied, and neither
      transition varies over the pH range studied. These results are discussed in terms
      of the cation contribution to the secondary structural stability in bR.

PMID- 11570883
TI  - Clusterin, a binding protein with a molten globule-like region.
AB  - Clusterin is a heterodimeric glycoprotein found in many tissues of the body and
      is the most abundant protein secreted by cultured rat Sertoli cells. The function
      of clusterin is unknown, but it has been associated with cellular injury, lipid
      transport, apoptosis, and it may be involved in the clearance of cellular debris
      caused by cell injury or death. Consistent with this last idea, clusterin has
      been shown to bind to a variety of molecules with high affinity including lipids,
      peptides, and proteins and the hydrophobic probe 1-anilino-8-naphthalenesulfonate
      (ANS). Given this variety of ligands, clusterin must have specific structural
      features that provide the protein with its promiscuous binding activity. Using
      sequence analyses, we show that clusterin likely contains three long regions of
      natively disordered or molten globule-like structures containing putative
      amphipathic alpha-helices. These disordered regions were highly sensitive to
      trypsin digestion, indicating a flexible nature. The effects of denaturation on
      the fluorescence of the clusterin-ANS complex were compared between proteins with
      structured binding pockets and molten globular forms of proteins. Clusterin bound
      ANS in a manner that was very similar to that of molten globular proteins.
      Furthermore, we found that, when bound to ANS, at least one cleavage site within
      the protease-sensitive disordered regions of clusterin was protected from trypsin
      digestion. In addition, we show that clusterin can function as a biological
      detergent that can solubilize bacteriorhodopsin. We propose that natively
      disordered regions with amphipathic helices form a dynamic, molten globule-like
      binding site and provide clusterin the ability to bind to a variety of molecules.

PMID- 11570884
TI  - Heme pocket disorder in myoglobin: reversal by acid-induced soft refolding.
AB  - The protein folding process of heme proteins entails generation of not only a
      correct global polypeptide structure, but also a correct, functionally competent
      heme environment. We employed a variety of spectroscopic approaches to probe the
      structure and dynamics of the heme pocket of a recombinant sperm whale myoglobin.
      The conformational characteristics were examined by circular dichroism, time
      resolved fluorescence spectroscopy, FTIR spectroscopy, and optical absorption
      spectroscopy in the temperature range 300-20 K. Each of these spectroscopic
      probes detected modifications confined exclusively to the heme pocket of the
      expressed myoglobin relative to the native protein. The functional properties
      were examined by measuring the kinetics of CO binding after flash-photolysis. The
      kinetics of the expressed myoglobin were more heterogeneous than those of the
      native protein. Mild acid exposure of the ferric derivative of the recombinant
      protein resulted in a protein with "nativelike" spectroscopic properties and
      homogeneous CO binding kinetics. The heme pocket modifications observed in this
      recombinant myoglobin do not derive from inverted heme. In contrast, when native
      apomyoglobin is reconstituted with the heme in vitro, the heme pocket disorder
      could be attributed exclusively to 180 degrees rotation of the bound heme [La
      Mar, G. N., Toi, H., and Krishnamoorthi, R. (1984) J. Am. Chem. Soc. 106, 6395
      6401; Light, W. R., Rohlfs, R. J., Palmer, G., and Olson, J. S. (1987) J. Biol.
      Chem. 262, 46-52]. We conclude that exposure to low pH decreases the affinity of
      globin for the heme and allows an extended conformational sampling or "soft
      refolding" to a nativelike conformation.

PMID- 11570885
TI  - Insulin stimulates increased catalytic activity of phosphoinositide-dependent
      kinase-1 by a phosphorylation-dependent mechanism.
AB  - Phosphoinositide-dependent kinase-1 (PDK-1) is a serine-threonine kinase
      downstream from PI 3-kinase that phosphorylates and activates other important
      kinases such as Akt that are essential for cell survival and metabolism. Previous
      reports have suggested that PDK-1 has constitutive catalytic activity that is not
      regulated by stimulation of cells with growth factors. We now show that insulin
      stimulation of NIH-3T3(IR) cells or rat adipose cells may significantly increase
      the intrinsic catalytic activity of PDK-1. Insulin treatment of NIH-3T3(IR)
      fibroblasts overexpressing PDK-1 increased both phosphorylation of recombinant
      PDK-1 in intact cells and PDK-1 kinase activity in an immune-complex kinase
      assay. Insulin stimulation of rat adipose cells also increased catalytic activity
      of endogenous PDK-1 immunoprecipitated from the cells. Both insulin-stimulated
      phosphorylation and activity of PDK-1 were inhibited by wortmannin and reversed
      by treatment with the phosphatase PP-2A. A mutant PDK-1 with a disrupted PH
      domain (W538L) did not undergo phosphorylation or demonstrate increased kinase
      activity in response to insulin stimulation. Similarly, a PDK-1 phosphorylation
      site point mutant (S244A) had no increase in kinase activity in response to
      insulin stimulation. Thus, the insulin-stimulated increase in PDK-1 catalytic
      activity may involve PI 3-kinase- and phosphorylation-dependent mechanisms. We
      conclude that the basal constitutive catalytic activity of PDK-1 in NIH-3T3(IR)
      cells and rat adipose cells can be significantly increased upon insulin
      stimulation.

PMID- 11570886
TI  - Characterization of the metal-substituted dipeptidyl peptidase III (rat liver).
AB  - Dipeptidyl peptidase III (DPP III) (EC 3.4.14.4), which has a HELLGH-E (residues
      450-455, 508) motif as the zinc binding site, is classified as a zinc
      metallopeptidase. The zinc dissociation constants of the wild type, Leu(453)
      deleted, and E508D mutant of DPP III at pH 7.4 were 4.5 (+/-0.7) x 10(-13), 5.8
      (+/-0.7) x 10(-12), and 3.2 (+/-0.9) x 10(-10) M, respectively. The recoveries of
      the enzyme activities by the addition of various metal ions to apo-DPP III were
      also measured, and Co(2+), Ni(2+), and Cu(2+) ions completely recovered the
      enzyme activities as did Zn(2+). The dissociation constants of Co(2+), Ni(2+),
      and Cu(2+) ions for apo-DPP III at pH 7.4 were 8.2 (+/-0.9) x 10(-13), 2.7 (+/
      0.3) x 10(-12), and 1.1 (+/-0.1) x 10(-14) M, respectively. The shape of the
      absorption spectrum of Co(2+)-DPP III was very similar to that of Co(2+)
      carboxypeptidase A or Co(2+)-thermolysin, in which the Co(2+) is bound to two
      histidyl nitrogens, a water molecule, and a glutamate residue. The absorption
      spectrum of Cu(2+)-DPP III is also very similar to that of Cu(2+)-thermolysin.
      The EPR spectrum and the EPR parameters of Cu(2+)-DPP III were very similar to
      those of Cu(2+)-thermolysin but slightly different from those of Cu(2+)
      carboxypeptidase A. The five lines of the superfine structure in the
      perpendicular region of the EPR spectrum in Cu(2+)-DPP III suggest that nitrogen
      atoms should coordinate to the cupric ion in Cu(2+)-DPP III. All of these data
      suggest that the donor set and the coordination geometry of the metal ions in DPP
      III, which has the HExxxH motif as the metal binding site, are very similar to
      those of the metal ions in thermolysin, which has the HExxH motif.

PMID- 11570887
TI  - Peroxidases inhibit nitric oxide (NO) dependent bronchodilation: development of a
      model describing NO-peroxidase interactions.
AB  - Recent studies demonstrate that nitric oxide (NO) serves as a physiological
      substrate for mammalian peroxidases [(2000) J. Biol. Chem. 275, 37524]. We now
      show that eosinophil peroxidase (EPO) and lactoperoxidase (LPO), peroxidases
      known to be enriched in airways of asthmatic subjects, function as a catalytic
      sink for NO, modulating its bioavailability and function. Using NO-selective
      electrodes and direct spectroscopic and rapid kinetic methods, we examined the
      interactions of NO with EPO and LPO compounds I and II and ferric forms and
      compared the results to those reported for myeloperoxidase. A unified kinetic
      model for NO interactions with intermediates of mammalian peroxidases during
      steady-state catalysis is presented that accommodates unique features observed
      with each member of the mammalian peroxidase superfamily. Potential functional
      consequences of peroxidase-NO interactions in asthma are investigated by
      utilizing organ chamber studies with tracheal rings. In the presence of
      pathophysiologically relevant levels of peroxidases and H(2)O(2), NO-dependent
      bronchodilation of preconstricted tracheal rings was reversibly inhibited. Thus,
      NO interaction with mammalian peroxidases may serve as a potential mechanism for
      modulating their catalytic activities, influencing the regulation of local
      inflammatory and infectious events in vivo.

PMID- 11570888
TI  - Structure and dynamics of the membrane-embedded domain of LmrAinvestigated by
      coupling polarized ATR-FTIR spectroscopy and (1)H/(2)H exchange.
AB  - Bacterial LmrA, an integral membrane protein of Lactococcus lactis, confers
      multidrug resistance by mediating active extrusion of a wide variety of
      structurally unrelated compounds. Similar to its eucaryotic homologue P-gp, this
      protein is a member of the ATP-binding cassette (ABC) superfamily. Different
      predictive models, based on hydropathy profiles, have been proposed to describe
      the structure of the ABC transporters in general and of LmrA in particular. We
      used polarized attenuated total reflection infrared spectroscopy, combined with
      limited proteolysis, to investigate the secondary structure and the orientation
      of the transmembrane segments of LmrA. We bring the first experimental evidence
      that the membrane-embedded domain of LmrA is composed of transmembrane-oriented
      alpha-helices. Furthermore, a new approach was developed in order to provide
      information about membrane domain dynamics. Monitoring the infrared linear
      dichroism spectra in the course of (1)H/(2)H exchange allowed to focus the
      recording of exchange rates on the membrane-embedded region of the protein only.
      This approach revealed an unusual structural dynamics, indicating high
      flexibility in this antibiotic binding and transport region.

PMID- 11570889
TI  - Two distinctive cell binding patterns by vacuolating toxin fused with glutathione
      S-transferase: one high-affinity m1-specific binding and the other lower-affinity
      binding for variant m forms.
AB  - The Helicobacter pylori VacA causes large intracellular vacuoles in epithelial
      cells such as HeLa or RK13 cells. Two major VacA forms, m1 and m2, divergent in
      an approximately 300 amino acid segment within the cell binding domain P58,
      display distinct cell-type specificity. Sequence analysis of four vacA alleles
      showed that a m1-like allele (61) and two m2 alleles (62 and v226) mainly
      differed in the midregion and that v225, a m1m2 chimera, was a natural double
      crossover from v226 and another allele. Each of these alleles was expressed as a
      soluble GST-VacA fusion that did not form a large oligomer. The recombinant VacA
      portion nevertheless assembled into higher ordered structures and possessed
      biological binding activity similar to that of the native VacA. A direct
      comparison of fusion-cell binding activity showed that m1 > m1m2 > m2 in HeLa
      cells, whereas there were more similar activities in RK13 cells. Vacuolating
      analyses of three forms revealed a positive correlation between cell binding
      activity and vacuolating activity. Moreover, the m1-type N-terminal half portion
      of the midregion was crucial for HeLa cell cytotoxicity. Kinetic, Scatchard, and
      inhibition analyses suggested the presence of at least two receptors: a m1-type
      specific high-affinity receptor (K(d) = approximately 5 nM) and a common VacA
      receptor interacting similarly with m1, m1m2, and m2 via a lower affinity (K(d) =
      45-67 nM). Expression of mainly the m1-type receptor on HeLa cells whereas both
      receptors on RK13 cells may account for distinct cell binding activity and
      therefore for cell-type specificity.

PMID- 11570890
TI  - Evidence for the involvement of Ala 166 in coupling Na(+) to sugar transport
      through the human Na(+)/glucose cotransporter.
AB  - We mutated residue 166, located in the putative Na(+) transport pathway between
      transmembrane segments 4 and 5 of human Na(+)/glucose cotransporter (hSGLT1),
      from alanine to cysteine (A166C). A166C was expressed in Xenopus laevis oocytes,
      and electrophysiological methods were used to assay function. The affinity for
      Na(+) was unchanged compared to that of hSGLT1, whereas the sugar affinity was
      reduced and sugar specificity was altered. There was a reduction in the turnover
      rate of the transporter, and in contrast to that of hSGLT1, the turnover rate
      depended on the sugar molecule. Exposure of A166C to MTSEA and MTSET, but not
      MTSES, abolished sugar transport. Accessibility of A166C to alkylating reagents
      was independent of protein conformation, indicating that the residue is always
      accessible from the extracellular surface. Sugar and phlorizin did not protect
      the residue from being alkylated, suggesting that residue 166 is not located in
      the sugar pathway. MTSEA, MTSET, and MTSES all changed the pre-steady-state
      kinetics of A166C, independent of pH, and sugars altered these kinetics. The
      inability of MTSEA-labeled A166C to transport sugar was reversed (with no major
      change in Na(+) and sugar affinity) if the positive charge on MTSEA was
      neutralized by increasing the external pH to 9.0. These studies suggest that the
      residue at position 166 is involved in the interaction between the Na(+) and
      sugar transport pathways.

PMID- 11570891
TI  - Mechanism of ascorbic acid oxidation by cytochrome b(561).
AB  - The 1 equiv reaction between ascorbic acid and cytochrome b(561) is a good model
      for redox reactions between metalloproteins (electron carriers) and specific
      organic substrates (hydrogen-atom carriers). Diethyl pyrocarbonate inhibits the
      reaction of cytochrome b(561) with ascorbate by modifying a histidine residue in
      the ascorbate-binding site. Ferri/ferrocyanide can mediate reduction of DEPC
      treated cytochrome b(561) by ascorbic acid, indicating that DEPC-inhibited
      cytochrome b(561) cannot accept electrons from a hydrogen-atom donor like
      ascorbate but can still accept electrons from an electron donor like
      ferrocyanide. Ascorbic acid reduces cytochrome b(561) with a K(m) of 1.0 +/- 0.2
      mM and a V(max) of 4.1 +/- 0.8 s(-1) at pH 7.0. V(max)/K(m) decreases at low pH
      but is approximately constant at pH >7. The rate constant for oxidation of
      cytochrome b(561) by semidehydroascorbate decreases at high pH but is
      approximately constant at pH <7. This suggests that the active site must be
      unprotonated to react with ascorbate and protonated to react with
      semidehydroascorbate. Molecular modeling calculations show that hydrogen bonding
      between the 2-hydroxyl of ascorbate and imidazole stabilizes the ascorbate
      radical relative to the monoanion. These results are consistent with the
      following mechanism for ascorbate oxidation. (1) The ascorbate monoanion binds to
      an unprotonated site (histidine) on cytochrome b(561). (2) This complex donates
      an electron to reduce the heme. (3) The semidehydroascorbate anion dissociates
      from the cytochrome, leaving a proton associated with the binding site. (4) The
      binding site is deprotonated to complete the cycle. In this mechanism, an
      essential role of the cytochrome is to bind the ascorbate monoanion, which does
      not react by outer-sphere electron transfer in solution, and complex it in such a
      way that the complex acts as an electron donor. Thermodynamic considerations show
      that no steps in this process involve large changes in free energy, so the
      mechanism is reversible and capable of fulfilling the cytochrome's function of
      equilibrating ascorbate and semidehydroascorbate.

PMID- 11570892
TI  - Kinetics of electron transfer from Q(a) to Q(b) in photosystem II.
AB  - The oxidation kinetics of the reduced photosystem II electron acceptor Q(A)(-)
      was investigated by measurement of the chlorophyll fluorescence yield transients
      on illumination of dark-adapted spinach chloroplasts by a series of saturating
      flashes. Q(A)(-) oxidation depends on the occupancy of the "Q(B) binding site",
      where this reaction reduces plastoquinone to plastoquinol in two successive
      photoreactions. The intermediate, one-electron-reduced plastosemiquinone anion
      Q(B)(-) remains tightly bound, and its reduction by Q(A)(-) may proceed with
      simple first-order kinetics. The next photoreaction, in contrast, may find the
      Q(B) binding site occupied by a plastoquinone, a plastoquinol, or neither of the
      two, resulting in heterogeneous Q(A)(-) oxidation kinetics. The assumption of
      monophasic Q(B)(-) reduction kinetics is shown to allow unambiguous decomposition
      of the observed multiphasic Q(A)(-) oxidation. At pH 6.5 the time constant for
      Q(A)(-) oxidation was found to be 0.2-0.4 ms with Q(B) in the site, 0.6-0.8 ms
      with Q(B)(-) in the site, 2-3 ms when the site is empty and Q(B) has to bind
      first, and of the order of 0.1 s if the site is temporarily blocked by the
      presence of Q(B)H(2) or other low-affinity inhibitors such as carbonyl cyanide m
      chlorophenylhydrazone (CCCP). Effects of pH and H(2)O/D(2)O exchange were found
      to be remarkably nonspecific. No influence of the S-states could be demonstrated.

PMID- 11570893
TI  - Thermodynamic stability of the bacteriorhodopsin lattice as measured by lipid
      dilution.
AB  - To determine the strength of noncovalent interactions that stabilize a membrane
      protein complex, we have developed an in vitro method for quantifying the
      dissociation of the bacteriorhodopsin (BR) lattice, a naturally occurring two
      dimensional crystal. A lattice suspension was titrated with a short- and long
      chain phosphatidylcholine mixture to dilute BR within the lipid bilayer. The
      fraction of BR in the lattice form as a function of added lipid was determined by
      visible circular dichroism spectroscopy and fit with a cooperative self-assembly
      model to obtain a critical concentration for lattice assembly. Critical
      concentration values of wild-type and mutant proteins were used to calculate the
      change in lattice stability upon mutation (DeltaDeltaG). By using this method, a
      series of mutant proteins was examined in which residues at the BR-BR interface
      were replaced with smaller amino acids, either Ala or Gly. Most of the mutant
      lattices were destabilized, with DeltaDeltaG values of 0.2-1.1 kcal/mol at 30
      degrees C, consistent with favorable packing of apolar residues in the membrane.
      One mutant, I45A, was stabilized by approximately 1.0 kcal/mol, possibly due to
      increased lipid entropy. The DeltaDeltaG values agreed well with previous in vivo
      measurements, except in the case of I45A. The ability to measure the change in
      stability of mutant protein complexes in a lipid bilayer may provide a means of
      determining the contributions of specific protein-protein and protein-lipid
      interactions to membrane protein structure.

PMID- 11570894
TI  - Studies on the structure of the G-protein-coupled receptor rhodopsin including
      the putative G-protein binding site in unactivated and activated forms.
AB  - Activation of G-protein coupled receptors (GPCR) is not yet understood. A recent
      structure showed most of rhodopsin in the ground (not activated) state of the
      GPCR, but the cytoplasmic face, which couples to the G protein in signal
      transduction, was not well-defined. We have determined an experimental three
      dimensional structure for rhodopsin in the unactivated state, which shows good
      agreement with the crystal structure in the transmembrane domain. This new
      structure defines the cytoplasmic face of rhodopsin. The G-protein binding site
      can be mapped. The same experimental approach yields a preliminary structure of
      the cytoplasmic face in the activated (metarhodopsin II) receptor. Differences
      between the two structures suggest how the receptor is activated to couple with
      transducin.

PMID- 11570895
TI  - Bacterial swarming: a biochemical time-resolved FTIR-ATR study of Proteus
      mirabilis swarm-cell differentiation.
AB  - Fourier transform infrared spectroscopy was applied to the study of the
      differentiation process undergone by Proteus mirabilis. This bacterium exhibits a
      remarkable dimorphism, allowing the cells to migrate on a solid substratum in a
      concerted manner yielding characteristic ring patterns. We performed an in situ
      noninvasive analysis of biochemical events occurring as vegetative cells
      differentiate into elongated, multinucleate, nonseptate, and hyperflagellated
      swarm cells. The major findings arising from this study are (i) the real-time
      monitoring of flagellar filament assembly, (ii) the evidence for de novo
      synthesis of qualitatively different lipopolysaccharides (LPS) and/or
      exopolysaccharides (EPS) constituting the slime into which bacteria swarm, and
      (iii) the alteration in the membrane fatty acid composition with a concomitant 10
      degrees C decrease in the gel/liquid crystal phase transition resulting in an
      elevated membrane fluidity in swarm cells at the growth temperature. The time
      course of events shows that the EPS-LPS syntheses are synchronous with membrane
      fatty acid alterations and occur about 1 h before massive flagellar filament
      assembly is detected. This study not only provided a time sketch of biochemical
      events involved in the differentiation process but also led to the identification
      of the major spectral markers of both vegetative and swarm cells. This
      identification will allow to resolve the time-space structure of P. mirabilis
      colonies by using infrared microscopy.

PMID- 11570896
TI  - Binding and activation of thiamin diphosphate in acetohydroxyacid synthase.
AB  - Acetohydroxyacid synthases (AHASs) are biosynthetic thiamin diphosphate- (ThDP)
      and FAD-dependent enzymes. They are homologous to pyruvate oxidase and other
      members of a family of ThDP-dependent enzymes which catalyze reactions in which
      the first step is decarboxylation of a 2-ketoacid. AHAS catalyzes the
      condensation of the 2-carbon moiety, derived from the decarboxylation of
      pyruvate, with a second 2-ketoacid, to form acetolactate or acetohydroxybutyrate.
      A structural model for AHAS isozyme II (AHAS II) from Escherichia coli has been
      constructed on the basis of its homology with pyruvate oxidase from Lactobacillus
      plantarum (LpPOX). We describe here experiments which further test the model, and
      test whether the binding and activation of ThDP in AHAS involve the same
      structural elements and mechanism identified for homologous enzymes. Interaction
      of a conserved glutamate with the N1' of the ThDP aminopyrimidine moiety is
      involved in activation of the cofactor for proton exchange in several ThDP
      dependent enzymes. In accord with this, the analogue N3'-pyridyl thiamin
      diphosphate does not support AHAS activity. Mutagenesis of Glu47, the putative
      conserved glutamate, decreases the rate of proton exchange at C-2 of bound ThDP
      by nearly 2 orders of magnitude and decreases the turnover rate for the mutants
      by about 10-fold. Mutant E47A also has altered substrate specificity, pH
      dependence, and other changes in properties. Mutagenesis of Asp428, presumed on
      the basis of the model to be the crucial carboxylate ligand to Mg(2+) in the
      "ThDP motif", leads to a decrease in the affinity of AHAS II for Mg(2+). While
      mutant D428N shows ThDP affinity close to that of the wild-type on saturation
      with Mg(2+), D428E has a decreased affinity for ThDP. These mutations also lead
      to dependence of the enzyme on K(+). These experiments demonstrate that AHAS
      binds and activates ThDP in the same way as do pyruvate decarboxylase,
      transketolase, and other ThDP-dependent enzymes. The biosynthetic activity of
      AHAS also involves many other factors beyond the binding and deprotonation of
      ThDP; changes in the ligands to ThDP can have interesting and unexpected effects
      on the reaction.

PMID- 11570897
TI  - A Streptomyces collinus thiolase with novel acetyl-CoA:acyl carrier protein
      transacylase activity.
AB  - Acetyl-CoA:acyl carrier protein (ACP) transacylase (ACT) activity has been
      demonstrated for the 3-ketoacyl-ACP synthase III (KASIII) which initiates fatty
      acid biosynthesis in the type II dissociable fatty acid synthases of plants and
      bacteria. Several lines of evidence have indicated the possibility of ACT
      activity being associated with proteins other than KASIII. Using a crude extract
      of Streptomyces collinus, we have resolved from KASIII an additional protein with
      ACT activity and subsequently purified it 85-fold in five chromatographic steps.
      The 45 kDa protein was shown by gel filtration to have a molecular mass of 185 +/
      35 kDa, consistent with a homotetrameric structure for the native enzyme. The
      corresponding gene (fadA) was cloned and sequenced and shown to encode a protein
      with amino acid sequence homology to type II thiolases. The fadA was expressed in
      Escherichia coli, and the resulting recombinant FadA enzyme purified by metal
      chelate chromatography was shown to have both ACT and thiolase activities.
      Kinetic studies revealed that in an ACT assay FadA had a substrate specificity
      for a two-carbon acetyl-CoA substrate (K(m) 8.7 +/- 1.4 microM) but was able to
      use ACPs from both type II fatty acid and polyketide synthases (Streptomyces
      glaucescens FabC ACP, K(m) 10.7 +/- 1.4 microM; E. coli FabC ACP, K(m) 8.8 +/- 2
      microM; FrenN ACP, K(m) 44 +/- 12 microM). In the thiolase assay kinetic analyses
      revealed similar K(m) values for binding of substrates acetoacetyl-CoA (K(m) 9.8
      +/- 0.8 microM) and CoA (K(m) 10.9 +/- 1.8 microM). A Cys92Ser mutant of FadA
      possessed virtually unchanged K(m) values for acetoacetyl-CoA and CoA but had a
      greater than 99% decrease in k(cat) for the thiolase activity. No detectable ACT
      activity was observed for the Cys92Ser mutant, demonstrating that both activities
      are associated with FadA and likely involve formation of the same covalent acetyl
      S-Cys enzyme intermediate. An ACT activity with ACP has not previously been
      observed for thiolases and in the case of the S. collinus FadA is significantly
      lower (k(cat) 3 min(-1)) than the thiolase activity of FadA (k(cat) 2170 min(
      1)). The ACT activity of FadA is comparable to the KAS activity and significantly
      higher than the ACT activity, reported for a streptomycete KASIII.

PMID- 11570898
TI  - The Institute of Medicine's report on medical error: implications for pathology.

PMID- 11570899
TI  - Low triglyceride levels affect calculation of low-density lipoprotein cholesterol
      values.

PMID- 11570901
TI  - Nongynecologic cytology turnaround time: a College of American Pathologists Q
      Probes study of 180 laboratories.
AB  - OBJECTIVES: To determine the turnaround time for nongynecologic cytology and to
      identify laboratory and specimen characteristics associated with variations in
      turnaround time. DESIGN AND SETTING: Prospective evaluation of nongynecologic
      cytology turnaround times in 180 laboratories. MAIN OUTCOME MEASURE:
      Nongynecologic cytology case turnaround time. RESULTS: Participants from 180
      laboratories submitted turnaround times for 16 950 nongynecologic cytology cases
      and submitted information describing their laboratories' practice characteristics
      relating to the processing of nongynecologic cytology specimens. Half of the
      participating laboratories had mean receipt to report turnaround times of 1.6
      calendar days or less and were able to complete 90% of their cases within 3.0
      calendar days. Ten percent of participants had mean turnaround times greater than
      3.2 days and required 6.0 or more days to report 90% of their cases. Longer
      turnaround times were associated with processing fluid and fine-needle aspiration
      specimens, issuing atypical/suspicious for malignancy and nondiagnostic
      diagnoses, having cytotechnologist students screen slides, having to contact the
      physician offices for additional information, having to retrieve prior case
      material for review, and having to perform cell blocks and/or special stains.
      CONCLUSION: There is an opportunity for laboratories to shorten nongynecologic
      turnaround time by altering certain laboratory practices.

PMID- 11570902
TI  - Method preferences and test accuracy of antimicrobial susceptibility testing:
      updates from the College of Amercian Pathologists Microbiology Surveys Program.
AB  - OBJECTIVE: To summarize the antimicrobial susceptibility testing results from the
      College of American Pathologists (CAP) Microbiology Surveys Program for 2000.
      Specifically, the frequency of tests used and the quantitative and qualitative
      (susceptibility category) accuracy were assessed. DESIGN: The CAP Microbiology
      Surveys challenged subscribers in 2000 with 3 well-characterized organisms for
      antimicrobial susceptibility testing in pure culture. Each laboratory was to use
      the test method and reporting procedures routinely applied to patient samples.
      The strains were National Committee for Clinical Laboratory Standards (NCCLS)
      quality control organisms with precisely defined antimicrobial susceptibility
      patterns and reproducibility. Results reported by participants (2685-2979/sample)
      were graded for categorical accuracy and quantitative performance by comparing
      reported minimal inhibitory concentrations (microg/mL) or zone diameters (mm)
      against quality control ranges published by the NCCLS. The appropriateness of
      reported drugs was determined in the context of the type and anatomic location of
      the infection. RESULTS: The tests most often used varied by the species of the
      organism and growth characteristics of the isolated strains. Nonfastidious, rapid
      growing Surveys unknowns (Escherichia coli ATCC 25922, Pseudomonas aeruginosa
      ATCC 27853) were most often tested with commercial systems (MicroScan, 42.0%
      42.4%; Vitek, 41.5%-43.0%) or with the standardized disk diffusion method (12.8%
      13.9%). In contrast, fastidious species, such as Streptococcus pneumoniae (ATCC
      49619), were predominantly tested by Etest (40.3%), followed by disk diffusion
      (27.6%) and MicroScan (23.2%). Categorical accuracy was essentially equal between
      dilution (98.9%) and diffusion (99.0%) methods. Among the minimal inhibitory
      concentration methods used to test penicillin against S pneumoniae, Etest method
      quantitative accuracy (96.3%) was greater than that of MicroScan (92.4%).
      Quantitative accuracy was greatest for dilution minimal inhibitory concentration
      methods, with more than 90% of results within NCCLS quality control ranges for
      nearly all reported antimicrobials. Reevaluations of quality control ranges may
      be needed for 4 to 7 agents, depending on method. Reporting errors were also
      detected in 2 areas: (1) reporting results for drugs not active at the site of
      infection and (2) reporting results for drugs tested with suboptimal methods
      without published NCCLS interpretive criteria. CONCLUSIONS: Antimicrobial
      susceptibility testing methods used in US laboratories were dominated by
      commercial products with relatively high accuracy (qualitative and quantitative).
      As available methods have become better suited to both fastidious and rapid
      growing species, reporting errors have assumed a higher level of concern to the
      CAP Surveys in an effort to minimize prescription errors.

PMID- 11570903
TI  - Solitary blood cultures: a College of American Pathologists Q-probes study of
      132,778 blood culture sets in 333 small hospitals.
AB  - OBJECTIVE: To determine the frequency with which solitary blood culture samples
      were submitted to laboratories serving small hospitals and to ascertain whether
      certain hospital practices relating to the performance of blood cultures were
      associated with lower solitary blood culture rates (SBCRs). DESIGN: Participants
      in the College of American Pathologists Q-Probes laboratory quality improvement
      program collected data prospectively on the numbers of solitary blood culture
      sets from adult patients submitted to their laboratories and answered questions
      about their institutions' practice characteristics relating to the collection of
      blood culture specimens. SETTING AND PARTICIPANTS: Three hundred thirty-three
      public and private institutions with a median occupied bed size of 57.
      Participants were located in the United States (n = 329), Canada (n = 3), and
      Australia (n = 1). MAIN OUTCOME MEASURE: The solitary blood culture rate was
      defined as the number of instances in which only 1 blood culture venipuncture was
      performed on an individual patient during a 24-hour period divided by the total
      number of blood culture venipunctures that were performed during the study
      period. RESULTS: Participants submitted data on 132 778 adult patient blood
      culture sets. The SBCRs were 3.4% or less in the top-performing 10% of
      participating institutions (90th percentile and above), 12.7% in the midrange of
      participating institutions (50th percentile), and 42.5% or more in the bottom
      performing 10% of participating institutions (10th percentile and below). In half
      the participating institutions, the SBCRs for inpatients were 8.3% or less and
      for outpatients, 22% or less. Solitary blood culture rates were lower for
      institutions in which phlebotomists rather than nonphlebotomists routinely
      collected blood culture specimens, in which internal policies required drawing at
      least 2 blood culture sets, in which hospital personnel contacted clinicians when
      their laboratories received requests for solitary blood culture sets, and in
      which quality control programs monitored SBCRs routinely. CONCLUSIONS: Hospitals
      can achieve SBCRs under 5%. Those hospitals with particularly high SBCRs may
      lower their rates by altering certain institutional practices.

PMID- 11570904
TI  - Malignant melanoma.
AB  - CONTEXT: The rapidly developing fields of melanoma research are revolutionizing
      the current concepts on melanoma etiology and pathogenesis and are introducing
      newer diagnostic techniques and potential therapeutic approaches. OBJECTIVES: To
      present the most current concepts on the etiology and pathogenesis of melanoma
      and to introduce the recent diagnostic techniques and the potential therapeutic
      approaches. METHODS: Data sources were reports on melanoma published in the
      English language literature and observations made using specimens available at
      Harvard University, Johns Hopkins Medical Center, Albany Medical College, Loyola
      University Medical Center, and University of Tennessee Health Science Center.
      RESULTS: Studies on melanoma containing chromosomal or genetic evaluation were
      selected for further analysis. Current clinical and pathologic categories with
      the reported genetic abnormalities were related to the latest information on
      pigment biology. The data extracted were used to develop a conceptual framework
      on the pathogenesis of melanoma; the generated model was then evaluated and used
      to suggest potential therapeutic approaches. CONCLUSIONS: (1) Melanoma is not
      genetically homogeneous, and the existing differences between the pathologic
      categories, particularly in areas such as type of growth phase (radial vs
      vertical growth), total vertical dimension, ulceration of primary tumor, and
      metastatic process, have profound prognostic and therapeutic implications. (2)
      Chromosomal aberrations and gene mutations are found in sporadic and familial
      melanomas; among the most important are those affecting the 9p21, which contains
      the p16 locus, a site known to be critical for normal progression of the cell
      cycle. Aberrant p16 expression is associated with more aggressive behavior. (3)
      Melanoma cells possess a remarkable repertoire of biosynthetic capacities
      represented by the production of hormones, growth factors, and their receptors
      that may sustain and accelerate tumor development and progression. For example,
      expression of the tumoral products alpha-melanocyte-stimulating hormone and
      adrenocorticotropic hormone is regulated in vitro by ultraviolet light, a known
      carcinogen. (4) Melanomas differ from other tumors in their intrinsic capability
      to express melanogenic enzymes with the corresponding structural proteins to
      actually synthesize melanin. Melanogenesis-related proteins are rapidly entering
      the clinical arena, being used not only as diagnostic markers, but also as
      potential targets for melanoma therapy.

PMID- 11570905
TI  - Preventing medical errors in point-of-care testing: security, validation,
      safeguards, and connectivity..
AB  - OBJECTIVES: o prevent medical errors, improve user performance, and enhance the
      quality, safety, and connectivity (bidirectional communication) of point-of-care
      testing. PARTICIPANTS: Group A included 37 multidisciplinary experts in point-of
      care testing programs in critical care and other hospital disciplines. Group B
      included 175 professional point-of-care managers, specialists, clinicians, and
      researchers. The total number of participants equaled 212. EVIDENCE: This study
      followed a systems approach. Expert specifications for prevention of medical
      errors were incorporated into the designs of security, validation, performance,
      and emergency systems. Additional safeguards need to be implemented through
      instrument software options and point-of-care coordinators. Connectivity will be
      facilitated by standards that eliminate deficiencies in instrument communication
      and device compatibility. Assessment of control features on handheld, portable,
      and transportable point-of-care instruments shows that current error reduction
      features lag behind needs. CONCENSUS PROCESS: Step 1: United States national
      survey and collation of group A expert requirements for security, validation, and
      performance. Step 2: Design of parallel systems for these functions. Step 3:
      Written critique and improvement of the error-prevention systems during 4
      successive presentations to group B participants over 9 months until system
      designs stabilized into final consensus form. CONCLUSIONS: The consensus process
      produced 6 conclusions for preventing medical errors in point-of-care testing:
      (1) adopt operator certification and validation in point-of-care testing
      programs; (2) implement security, validation, performance, and emergency systems
      on existing and new devices; (3) require flexible, user-defined error-prevention
      system options on instruments as a prerequisite to federal licensing of new
      diagnostic tests and devices; (4) integrate connectivity standards for
      bidirectional information exchange; (5) preserve fast therapeutic turnaround time
      of point-of-care test results; and (6) monitor invalid use, operator competence,
      quality compliance, and other performance improvement indices to reduce errors,
      thereby focusing on patient outcomes.(Arch Pathol Lab Med. 2001;1307-1315)

PMID- 11570906
TI  - Immunohistochemical analysis of nuclear versus cytoplasmic staining of WT1 in
      malignant mesotheliomas and primary pulmonary adenocarcinomas.
AB  - CONTEXT: Previous studies have indicated certain immunohistochemical markers,
      including WT1, may be helpful in distinguishing adenocarcinomas from
      mesotheliomas, but to date there are no reliable, widely accepted, commercially
      available antibodies positive in mesotheliomas and negative in adenocarcinomas.
      We compared the nuclear and cytoplasmic staining patterns of WT1 in these 2
      malignancies using a commercially available antibody and examined the expression
      of 2 other previously reported positive markers, calretinin and thrombomodulin.
      METHODS: Sixty-seven mesotheliomas and 51 adenocarcinomas, all paraffin embedded,
      were retrieved from recent case files. The diagnosis of mesothelioma was based on
      typical clinical and morphologic features, as well as immunohistochemistry;
      electron microscopy had been performed on 16 cases. The diagnosis of
      adenocarcinoma was based on typical light microscopic findings and a positive
      stain for mucin. Commercially available antibodies to WT1, thrombomodulin, and
      calretinin were applied. Because of the conflict surrounding calretinin, 2
      anticalretinin antibodies (from Chemicon Inc and Zymed Laboratories) were
      utilized. RESULTS: Fifty of 67 mesotheliomas showed strong nuclear staining with
      WT1. No adenocarcinomas (0/51) showed nuclear staining. Twenty-three of 67
      mesotheliomas were positive for thrombomodulin, and 35 of 67 mesotheliomas were
      positive for calretinin with the Chemicon antibody. Nine of 15 mesotheliomas were
      positive for calretinin with the Zymed antibody. CONCLUSIONS: Thrombomodulin and
      calretinin did not prove useful in discriminating between mesotheliomas and
      adenocarcinomas. The degree of positivity with calretinin may be dependent on the
      specific antibody utilized. Nuclear staining for WT1 is highly specific for
      mesothelioma and, in the appropriate clinical setting, can be a helpful adjunct
      in the distinction between adenocarcinomas and mesotheliomas.

PMID- 11570907
TI  - Expression of protein gene product 9.5 in epithelioid and conventional malignant
      peripheral nerve sheath tumors.
AB  - CONTEXT: Due to the frequent lack of S100 protein expression in malignant
      peripheral nerve sheath tumors (MPNSTs), especially the epithelioid variant,
      these tumors are difficult to diagnose without the aid of electron microscopy or
      a clinical history of neurofibromatosis. METHODS: Protein gene product 9.5
      (PGP9.5), a broad neural marker, is expressed in nerve fibers and neurons of both
      the peripheral and central nervous systems. We compared its expression to that of
      S100 protein in 16 cases of MPNST. As controls, 6 monophasic synovial sarcomas, 9
      leiomyosarcomas, and 5 dermatofibrosarcoma protuberans were included. RESULTS:
      Expression of PGP9.5 was seen in 15 MPNSTs, with 3 to 4+ positivity in the
      majority of the cases. Ten cases, 2 epithelioid and 8 conventional MPNSTs, were
      reactive with PGP9.5, but were negative for S100 protein. Five cases were
      immunoreactive for both S100 protein and PGP9.5. One case was negative for PGP9.5
      but demonstrated focal S100 protein positivity. Expression of PGP9.5 was seen in
      4 of 6 synovial sarcomas, 3 of 9 leiomyosarcomas, and none of 5
      dermatofibrosarcoma protuberans. CONCLUSION: Although PGP9.5 is not a specific
      marker for MPNST, it is a more sensitive marker than S100 protein (94% vs 38%).
      When there is a lack of S100 protein expression and a broad panel of
      immunostains, such as cytokeratin, epithelial membrane antigen, and smooth muscle
      actin, yields only focal or equivocal staining, PGP9.5 is a useful diagnostic
      adjunct in confirming the neural origin of a spindle cell sarcoma.

PMID- 11570908
TI  - Bcl-2, Bcl-x, and Bax expression by immunohistochemistry in inclusion body
      myositis: a study of 27 cases.
AB  - CONTEXT: Bcl-2, Bcl-x, and Bax are among the variety of proteins that have been
      described as being involved in the regulation of apoptotic cell death. Bcl-2 and
      Bcl-x(L) inhibit apoptosis, and Bax is proapoptotic. OBJECTIVE: To evaluate the
      expression of Bcl-2, Bcl-x, and Bax in inclusion body myositis (IBM).Design.-We
      examined muscle specimens from 27 patients (17 men, 10 women) with IBM to
      evaluate Bcl-2, Bcl-x, and Bax expression by immunohistochemistry. RESULTS:
      Patient ages ranged from 29 to 80 years (mean 62.2 years). All biopsies were
      marked by endomysial chronic inflammation, muscle fiber necrosis, and
      regeneration. Rimmed (autophagic) vacuoles were present in all cases. Ragged red
      fibers were noted in 4 biopsies (15%), and cytochrome oxidase-deficient fibers
      were found in 10 biopsies (37%). Ultrastructural evidence of intranuclear or
      cytoplasmic tubulofilamentous inclusions, confirming the diagnosis of IBM, were
      noted in all cases. Paracrystalline mitochondrial inclusions were seen in 5
      biopsies (18.5%). Inflammatory cells stained positively with Bcl-2 in all
      biopsies, Bax in 26 biopsies (96%), and Bcl-x in 8 biopsies (30%). Degenerating
      muscle fibers were highlighted with Bax in 24 biopsies (89%), Bcl-2 in 2 biopsies
      (7%), and Bcl-x in 3 biopsies (11%). Regenerative muscle fibers were noted to
      stain with Bax in 24 muscles (89%), Bcl-2 in 21 muscles (78%), and Bcl-x in 4
      muscles (15%). Rimmed vacuoles were highlighted by Bax in 24 biopsies (89%) and
      only rarely by Bcl-2 (n = 2, 7%) and Bcl-x (n = 3, 11%). A subsarcolemmal
      staining pattern was observed in 21 biopsies (78%) with Bax, 6 biopsies (22%)
      with Bcl-2, and only 1 biopsy (4%) with Bcl-x. CONCLUSIONS: (1) Bax
      (proapoptotic) immunostaining highlighted most autophagic vacuoles; (2)
      subsarcolemmal Bax and Bcl-2 immunoreactivity may be associated with
      mitochondrial defects that are commonly noted in IBM; (3) Bcl-2 and Bax
      immunoreactivity were not confined to degenerating muscle fibers and in fact
      appeared to be expressed more commonly in regenerating fibers, suggesting that
      their expression may be independent of apoptosis in the setting of IBM.

PMID- 11570909
TI  - Obliterative muscularization of the small bowel submucosa in Crohn disease: a
      possible mechanism of small bowel obstruction.
AB  - CONTEXT: The pathology of small bowel obstruction in Crohn disease has not been
      studied extensively. Stricture formation has been attributed mainly to fibrosis,
      although muscularization of the submucosa has been discussed previously.
      OBJECTIVE: To identify additional pathologic changes in Crohn disease that could
      be involved in the formation of strictures. DESIGN: We reviewed 50 ileal
      resections from patients with Crohn disease. The histopathologic slides were
      reviewed initially without knowledge of the macroscopic or clinical findings. We
      identified an unusual muscular proliferation that we refer to as obliterative
      muscularization of the submucosa, defined as a thick and continuous muscle layer
      from the mucosal base to the muscularis propria that is at least 1 cm in length.
      Subsequently, histopathologic findings were correlated with macroscopic and
      clinical findings. RESULTS: Obliterative muscularization of the submucosa was
      present in 14 specimens, and in 11 of these 14 it was topographically restricted
      to strictures. Submucosal fibrosis was observed in sections from adjacent
      regions. Obliterative muscularization of the submucosa, including thick-walled
      vessels and hyperplastic nerves but not prominent scarring, was more common in
      specimens with strictures; the difference was statistically significant (P
      <.001). CONCLUSIONS: Obliterative muscularization of the submucosa may be
      pathogenetically involved in the formation of strictures either directly by
      causing a sustained spasm, or indirectly by minimizing the vasoprotective role of
      the submucosa, impairing repair and enhancing scarring.

PMID- 11570911
TI  - The role of fine-needle aspiration biopsy in the diagnosis and management of
      juvenile hemangioma of the parotid gland and cheek.
AB  - BACKGROUND: The current recommendation for the management of juvenile hemangiomas
      (JH) is to delay treatment in the hope of spontaneous regression. However,
      accurate diagnosis is necessary before considering conservative management.
      Traditionally, the diagnosis of JH has required excisional biopsy. The cytology
      literature on this relatively rare neoplasm is sparse. OBJECTIVE: To present our
      experience with fine-needle aspiration in the diagnosis and management of JH.
      DESIGN: Three cases with a cytologic diagnosis consistent with JH of the parotid
      gland and cheek were identified from our cytopathology files. Aspirate smears,
      immunohistochemical studies, computed tomographic scan findings, and clinical
      follow-up were reviewed. RESULTS: Patients were female infants ranging in age
      from 3 to 9 months and presented with an oval firm mass (size range, 2.0-5.0 cm)
      involving the parotid gland (2 cases) and cheek (1 case). Computed tomographic
      scan with contrast demonstrated homogeneous enhancement. Aspirate smears revealed
      spindle-shaped cells in sheets and clusters in a background of blood. The parotid
      gland aspirates and cell block preparations revealed ductal structures entrapped
      in sheets of spindle-shaped cells. Immunohistochemical studies revealed prominent
      vascular spaces lined by CD34 and factor VIII-positive flattened endothelial
      cells. The diagnosis of JH was rendered on the basis of the cytologic findings in
      conjunction with the radiologic and clinical findings. On clinical follow-up (8
      24 months), none of the patients has shown any progression of the lesion.
      CONCLUSIONS: Fine-needle aspiration, in conjunction with imaging studies, is a
      useful tool in the diagnosis and management of JH. It eliminates the need for
      surgical excision for diagnostic purposes and allows for clinical follow-up of
      patients with JH.

PMID- 11570910
TI  - Expression of thyroid transcription factor-1 and other markers in sclerosing
      hemangioma of the lung.
AB  - CONTEXT: Sclerosing hemangioma of the lung is well characterized histologically,
      but the line of differentiation expressed by the tumor cells has been unclear.
      Despite the implication by its name of a vascular neoplasm, sclerosing hemangioma
      is considered by most authorities to be an epithelial tumor, possibly related to
      the pulmonary epithelium. OBJECTIVES: To determine the line of differentiation of
      the tumor cells with immunohistochemistry and to review the related literature.
      DESIGN: Nine cases of histologically typical pulmonary sclerosing hemangioma were
      studied with pan-epithelial (epithelial membrane antigen [EMA] and CAM 5.2),
      endothelial (CD31), neuroendocrine (chromogranin A), and pulmonary epithelial
      markers (thyroid transcription factor-1 and PE10). Staining intensity was
      separately evaluated in the pale cells of the solid areas and the cells lining
      the papillary structures. RESULTS: Both cell types were positive for thyroid
      transcription factor-1 and EMA in all cases (100%). Thyroid transcription factor
      1 showed diffuse strong staining, and EMA staining varied from focal weak to
      diffuse strong. The pale cells showed focal staining for keratin (CAM 5.2) in 2
      (28%) of 7 cases, and for PE10 in 5 (62%) of 8 cases. The papillary lining cells
      were at least focally positive with CAM 5.2 and PE10 in all cases (100%).
      Reactions for chromogranin and CD31 were negative in both cell types in every
      case. The number of PE10- or CAM 5.2-positive papillary lining cells was less
      than the number of EMA-positive papillary lining cells. CONCLUSION: The uniform
      positivity for EMA is consistent with the notion that the tumor cells of
      sclerosing hemangioma are epithelial, and the strong thyroid transcription factor
      1 positivity suggests differentiation toward pulmonary epithelium. The papillary
      lining cells expressing EMA as well as PE10 or CAM 5.2 likely represent entrapped
      metaplastic alveolar epithelium, whereas the papillary lining cells expressing
      only EMA more likely constitute true neoplastic cells similar to those in the
      solid areas.

PMID- 11570912
TI  - Nesidioblastosis coexisting with islet cell tumor and intraductal papillary
      mucinous hyperplasia.
AB  - A coexisting of intraductal papillary mucinous hyperplasia (IPMH) and islet cell
      tumor with nesidioblastosis of the pancreas in a 51-year-old man is reported. All
      of the clinical data indicated an insulinoma. A distal pancreatectomy was
      performed. A discrete mass measuring 1.9 x 2.0 cm was grossly identified in the
      tail of the pancreas. There were no other gross lesions. An islet cell tumor with
      nesidioblastosis was confirmed by immunostains and ultrastructural study. In
      addition, an IPMH was found that involved mainly branches of the pancreatic duct.
      The islet cell tumor and IPMH were topographically separated; however, there was
      a histologically intimate relationship between the nesidioblastosis and the IPMH.
      These findings indicate that the IPMH may have derived from autocrine and
      paracrine influences on the existing duct epithelial cells. To the best of our
      knowledge, this is the first report of nesidioblastosis coexisting with islet
      cell tumor and IPMH.

PMID- 11570913
TI  - Rosai-Dorfman disease of the parotid gland: cytologic and histopathologic
      findings with immunohistochemical correlation.
AB  - Rosai-Dorfman disease is a rare histiocytic proliferative disorder of unknown
      origin and a distinct clinicopathologic entity also known as sinus histiocytosis
      with massive lymphadenopathy. The disease can involve extranodal tissues and
      rarely can present as salivary gland enlargement without significant
      lymphadenopathy. Involvement of the extranodal head and neck sites appears to be
      more common in patients with immunologic abnormalities. The disease was first
      described in 4 patients in 1969, and with later descriptions of more patients,
      the disease was established as a well-defined clinicopathologic entity. The
      characteristic pathologic feature of this disease is proliferation of distinctive
      histiocytic cells that demonstrate emperipolesis in the background of a mixed
      inflammatory infiltrate, consisting of moderately abundant plasma cells and
      lymphocytes. Fine-needle aspiration biopsy can be helpful in establishing the
      correct diagnosis, since surgical treatment is not necessary other than obtaining
      tissue for definitive diagnosis. We describe cytologic, histopathologic, and
      immunohistochemical features of a case of Rosai-Dorfman disease that involved a
      major salivary gland without significant lymphadenopathy in a 48-year-old patient
      with systemic lupus erythematosus. We also briefly discuss possible causes and
      pathogenesis and review the literature.

PMID- 11570914
TI  - An unusual presentation of calciphylaxis due to primary hyperparathyroidism.
AB  - We present the case of a 69-year-old woman with calciphylaxis due to primary
      hyperparathyroidism. A 0.5-g parathyroid adenoma was surgically removed, which
      resulted in complete recovery of the patient. Review of the literature revealed 7
      other cases of calciphylaxis due to primary hyperparathyroidism and showed that
      prompt surgical removal of the autonomous parathyroid gland lesion results in
      clinical recovery of calciphylactic skin lesions.

PMID- 11570915
TI  - Urothelial and prostate carcinoma metastasizing to the same lymph node: a case
      report and review of the literature.
AB  - We report herein a case of a collision tumor composed of high-grade urothelial
      carcinoma and a Gleason grade 3+4 prostate adenocarcinoma metastasizing to the
      same lymph node. After the patient underwent cystoprostatectomy for known
      urothelial carcinoma, he was incidentally discovered to have a second primary
      prostate tumor. Lymph node examination revealed that one node appeared to have
      metastatic foci from both primary tumors. The presence of 2 tumor types colliding
      in the same lymph node was confirmed using immunohistochemical stains, including
      monoclonal carcinoembryonic antigen, prostate-specific antigen, prostatic acid
      phosphatase, cytokeratins 7 and 20, and CD57. We also stained both primary tumors
      with the same panel as an internal control. Although 2 similar collision tumors
      have been reported in the literature in the past, neither used a battery of
      immunohistochemical stains to definitively distinguish one tumor from the other.
      Herein, we review the literature on urothelial and prostate collision tumors and
      some of the special stains used to distinguish them.

PMID- 11570916
TI  - Extraskeletal Ewing sarcoma in a 77-year-old woman.
AB  - Extraskeletal Ewing sarcoma (EES) is a rare soft tissue tumor that is
      morphologically indistinguishable from Ewing sarcoma of bone. It is usually found
      in young people, but several cases have occurred in patients older than 50 years.
      The differential diagnoses include other small, blue round cell tumors (SBRCTs)
      and other members of the Ewing family of tumors such as the primitive
      neuroectodermal tumor. We present a case of EES in the left inguinal region of a
      77-year-old woman. The tumor was distinguished from other SBRCTs by lack of
      immunoreactivity for epithelial, lymphoid, vascular, neuroendocrine, neural,
      histiocytic, and muscle markers. Primitive neuroectodermal tumor was excluded
      because of the lack of neural differentiation by histologic analysis,
      immunohistochemistry, and electron microscopy. Extraskeletal Ewing sarcoma was
      confirmed by characteristic features on histologic analysis, histochemistry,
      immunohistochemistry, and electron microscopy and by the presence of the
      t(11;22)(q24;q12) fusion transcript detected by reverse transcriptase-polymerase
      chain reaction. This case serves to remind the reader that EES is not a tumor
      that occurs exclusively in young patients.

PMID- 11570917
TI  - p53 Mutation in adenocarcinoma arising in retrorectal cyst hamartoma (tailgut
      cyst): report of 2 cases--an immunohistochemistry/immunoperoxidase study.
AB  - Retrorectal cyst hamartoma (RCH) is a rare benign cystic lesion located in the
      retrorectal space. Malignancy arising in such lesions is very uncommon. In this
      study, 2 cases of mucinous adenocarcinoma arising in RCH are presented. In one
      case, dysplastic epithelium lined the cyst wall, surrounding the area of
      carcinoma and suggesting a dysplasia-carcinoma progression in RCH. Adenocarcinoma
      and the dysplastic epithelium were strongly positive for p53 and Ki-67 and showed
      negative staining for p21 by immunohistochemistry. These findings are suggestive
      of a mutation in the p53 gene in the adenocarcinoma and in dysplastic epithelium
      lining the cysts, similar to the dysplasia-carcinoma sequence described for the
      development of colonic adenocarcinoma.

PMID- 11570918
TI  - Malignancies arising in oncocytic schneiderian papillomas: a report of 2 cases
      and review of the literature.
AB  - Oncocytic schneiderian papillomas (OSPs) are uncommon benign neoplasms that arise
      from the sinonasal schneiderian epithelium. Malignancies arising in OSPs are
      rare, and, to our knowledge, only 14 such instances have been reported in the
      medical literature. We report 2 additional cases--a small cell carcinoma and a
      sinonasal undifferentiated carcinoma arising in OSPs and presenting synchronously
      with the benign neoplasm. The potential for malignant transformation in OSPs is
      small, but warrants that these papillomas be completely excised to exclude a
      coexisting carcinoma.

PMID- 11570919
TI  - Pseudopapillary solid cystic tumor arising from an extrapancreatic site.
AB  - A case of pseudopapillary solid cystic tumor arising in the omentum of a 46-year
      old woman is presented. A well-defined, encapsulated tumor measuring 5.2 x 4.0 x
      4.0 cm was histologically characterized by a combination of solid and
      pseudopapillary growth patterns of tumor cells with abundant pale-to-eosinophilic
      cytoplasm. No pancreatic tissue was observed within or adjacent to the tumor.
      Immunohistochemically, the tumor was positive for vimentin, epithelial membrane
      antigen, and alpha1-antichymotrypsin. Ultrastructurally, the tumor cells
      contained electron dense granules of variable sizes, most likely representing
      lysosomes. Flow cytometry showed a diploid DNA content with a high S-phase
      fraction. The patient was well without recurrence 3 months after diagnosis. It is
      important to include pseudopapillary solid cystic tumor in the differential
      diagnosis of omental tumors.

PMID- 11570920
TI  - Invasive secretory (juvenile) carcinoma arising in ectopic breast tissue of the
      axilla.
AB  - Mammary carcinoma arising in ectopic breast tissue is an uncommon occurrence.
      Most reported cases have involved ductal carcinoma, but other types, such as
      medullary, papillary, and lobular carcinomas, have been described. For
      pathologists, the diagnosis of mammary carcinoma arising in ectopic breast tissue
      can be difficult, especially in the axilla, where carcinoma of adnexal origin
      must be excluded. We describe a 46-year-old woman who developed invasive
      (juvenile) secretory carcinoma in ectopic right axillary breast tissue and
      micrometastatic carcinoma in an ipsilateral axillary lymph node. The carcinoma
      arose in a right axillary mass that had been present for 8 years, from which she
      had secreted fluid during prior breast-feeding. To our knowledge, this is the
      first report of secretory carcinoma arising in axillary breast tissue to be
      documented in the current literature.

PMID- 11570921
TI  - Achondrogenesis type IB: agenesis of cartilage interterritorial matrix as the
      link between gene defect and pathological skeletal phenotype.
AB  - Achondrogenesis type IB is a lethal osteochondrodysplasia caused by mutations in
      the diastrophic dysplasia sulfate transporter gene. How these mutations lead to
      the skeletal phenotype is not known. Histology of plastic-embedded skeletal fetal
      achondrogenesis type IB samples suggested that interterritorial epiphyseal
      cartilage matrix was selectively missing. Cartilage was organized in "chondrons"
      separated by cleft spaces; chondrocyte seriation, longitudinal septa, and, in
      turn, mineralized cartilaginous septa were absent. Agenesis of interterritorial
      matrix as the key histologic change was confirmed by immunohistology using
      specific markers of territorial and interterritorial matrix. Biglycan-enriched
      territorial matrix was preserved; decorin-enriched interterritorial areas were
      absent, although immunostaining was observed within chondrocytes. Thus, in
      achondrogenesis type IB: (1) a complex derangement in cartilage matrix assembly
      lies downstream of the deficient sulfate transporter activity; (2) the severely
      impaired decorin deposition participates in the changes in matrix organization
      with lack of development of normal interterritorial matrix; and (3) this change
      determines the lack of the necessary structural substrate for proper endochondral
      bone formation and explains the severe skeletal phenotype.

PMID- 11570922
TI  - Firm erythematous papules of scalp in a woman with a history of breast cancer.

PMID- 11570923
TI  - A large subcutaneous cyst in a Haitian man.

PMID- 11570924
TI  - An unusual tumor of the urinary bladder.

PMID- 11570925
TI  - Cauda equina syndrome in a 65-year-old man, status post-bone marrow transplant
      for chronic myeloid leukemia.

PMID- 11570926
TI  - A retroperitoneal mass in a 44-year-old woman with recurrent myocardial
      infarctions.

PMID- 11570927
TI  - Abnormal uterine bleeding.

PMID- 11570928
TI  - Soft tissue cyst secondary to bullet retention.

PMID- 11570929
TI  - Rhinosporidiosis: an unusual affliction.

PMID- 11570930
TI  - Flaming plasma cells.

PMID- 11570931
TI  - The effects of live, taped, and no music on people experiencing posttraumatic
      amnesia.
AB  - This study compared the effects of live, taped, and no music, on agitation and
      orientation levels of people experiencing posttraumatic amnesia (PTA).
      Participants (N = 22) were exposed to all 3 conditions, twice over 6 consecutive
      days. Songs used in the live and taped music conditions were identical and were
      selected based on participants' own preferred music. Pre and posttesting was
      conducted for each condition using the Agitated Behavior Scale (Corrigan, 1989)
      and the Westmead PTA Scale (Shores, Marosszeky, Sandanam, Batchelor, 1986).
      Participants' memory for the music used was also tested and compared with their
      memory for pictorial material presented in the Westmead PTA Scale. Results
      indicate that music significantly reduced agitation (p <.0001) and enhanced
      orientation (p <.001) however, the difference between live and taped music was
      not significant (p =.7). The mean number of pictures in the Westmead PTA scale
      recalled was 0.84 and the mean number of music selections recalled was 1.22 but
      this difference was not significant (p =.7). However, the trend suggests that
      music selections are more easily encoded in memory and then retrieved on request,
      than that of pictures. Analysis of responses in a follow-up assessment
      questionnaire showed that 77% of participants recalled the music program while in
      PTA, indicating that it reached the memory threshold. Sixty-four percent recalled
      the live music and 55% recalled the taped music condition however this difference
      was not significant (p =.7). Results suggest that music therapy programs have an
      important role to play in the management of people in PTA.

PMID- 11570932
TI  - Emotional change processes in music-assisted reframing.
AB  - Affective processes are critical to understanding and promoting lasting
      therapeutic change. Using a sample of 40 anxious adults, the researchers examined
      the use of music to increase affective modification and emotional restructuring
      in a cognitive reframing intervention. Subjects were assigned to either a typical
      reframing intervention or a music-assisted reframing intervention. Using the
      State-Trait Anxiety Inventory, Subjective Units of Distress Scale, Depression
      Adjective Checklist, and a Think-Aloud measure, the groups were compared on basis
      of anxiety-reduction, affective modification, and imagery vividness. Results
      indicate that the music-assisted reframing intervention was more efficacious than
      the typical reframing intervention in reducing anxiety, modifying affect, and
      promoting imagery-vividness.

PMID- 11570933
TI  - The effects of group music therapy on mood states and cohesiveness in adult
      oncology patients.
AB  - The purpose of the current investigation was to examine the efficacy of a music
      therapy protocol on mood states and levels of group cohesiveness in adult
      oncology patients. Eleven oncology patients in 2 groups (ages 30 to 84 years)
      took part in the study over a 10-week period of time (10 participants completed
      the study). During that period, participants took part in 8 music therapy
      sessions consisting of 2 types of interventions: (a) 4 "music making" sessions
      (where the mechanism for change included the process of making music) and (b) 4
      "music responding" sessions (where the mechanism included the process of
      responding to music). The two types of music therapy sessions and their
      effectiveness on improving mood states and group cohesiveness were examined. The
      Profile of Mood States-Short Form (POMS-SF) was used to assess changes in
      participants' mood states. A content analysis, attendance records, and a
      questionnaire were used to assess levels of group cohesiveness. Results showed
      significant improvement in mood state scores (from presession levels to
      postsessions levels) after involvement in all music therapy sessions. Similar
      significant findings were found within each of the "music making" and "music
      responding" conditions but no differences were found when comparisons were made
      between those conditions. No statistically significant effects were found with
      respect to group cohesiveness measures. Study implications and future research
      directions are discussed.

PMID- 11570934
TI  - The effects of an early intervention music curriculum on prereading/writing.
AB  - This study evaluated the effects of music sessions using a curriculum designed to
      enhance the prereading and writing skills of 25 children aged 4 to 5 years who
      were enrolled in Early Intervention and Exceptional Student Education programs.
      This study was a replication of the work of Standley and Hughes (1997) and
      utilized a larger sample size (n = 50) in order to evaluate the efficacy of a
      music curriculum designed specifically to teach prereading and writing skills
      versus one that focuses on all developmental areas. Both the experimental (n =
      25) and control (n = 25) groups received two 30-minute sessions each week for an
      entire school year for a minimum of 60 sessions per group. The differentiating
      factors between the two groups were the structure and components of the musical
      activities. The fall sessions for the experimental group were focused primarily
      on writing skills while the spring sessions taught reading/book concepts. Music
      sessions for the control group were based purely on the thematic material, as
      determined by the classroom teacher with purposeful exclusion of all preliteracy
      concepts. All participants were pretested at the beginning of the school year and
      posttested before the school year ended. Overall, results demonstrated that music
      sessions significantly enhanced both groups' abilities to learn prewriting and
      print concepts. However, the experimental group showed significantly higher
      results on the logo identification posttest and the word recognition test.
      Implications for curriculum design and academic and social applications of music
      in Early Intervention programs are discussed.

PMID- 11570935
TI  - William Osler and The Fixed Period: conflicting medical and popular ideas about
      old age.
AB  - William Osler (1849-1919) has long been hailed as one of the most illustrious
      physicians in our history. Yet, Osler's claim to fame outside the medical
      profession in the early 20th century was through what became known as The Fixed
      Period controversy about the usefulness of old men. In 1905, as the 55-year-old
      Osler said farewell to Johns Hopkins University School of Medicine before leaving
      for Oxford University in England he remarked that men older than 60 years should
      be retired. He further mentioned a suggestion, which he attributed to Anthony
      Trollope's novel The Fixed Period, that men older than that age be chloroformed.
      This article explores the public reaction to Osler in the context of early 20th
      century American ideas about old age and manhood. As our society has changed over
      the past century, so have our ideas about old age. The Fixed Period incident
      offers us an opportunity to explore the relationship between medical and popular
      ideas about old age. This historical perspective allows us to see that physicians
      have not always had authority over old age and that public understanding and
      medical pronouncements on old age do not necessarily match.

PMID- 11570936
TI  - Evidence- and consensus-based practice guidelines for the diagnosis of irritable
      bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) presents a significant diagnostic and
      management challenge for primary care practitioners. Improving the accuracy and
      timeliness of diagnosis may result in improved quality and efficiency of care.
      OBJECTIVE: To systematically appraise the existing diagnostic criteria and
      combine the evidence with expert opinion to derive evidence- and consensus-based
      guidelines for a diagnostic approach to patients with suspected IBS. METHODS: We
      performed a systematic literature review (January 1966-April 2000) of
      computerized bibliographic databases. Articles meeting explicit inclusion
      criteria for diagnostic studies in IBS were subjected to critical appraisal,
      which formed the basis of guideline statements presented to an expert panel. To
      develop a diagnostic algorithm, an expert panel of specialists and primary care
      physicians was used to fill in gaps in the literature. Consensus was developed
      using a modified Delphi technique. RESULTS: The systematic literature review
      identified only 13 published studies regarding the effectiveness of competing
      diagnostic approaches for IBS, the accuracy of diagnostic tests, and the internal
      validity of current diagnostic symptom criteria. Few studies met accepted
      methodological criteria. While symptom criteria have been validated, the utility
      of endoscopic and other diagnostic interventions remains unknown. An analysis of
      the literature, combined with consensus from experienced clinicians, resulted in
      the development of a diagnostic algorithm relevant to primary care that
      emphasizes a symptom-based diagnostic approach, refers patients with alarm
      symptoms to subspecialists, and reserves radiographic, endoscopic, and other
      tests for referral cases. The resulting algorithm highlights the reliance on
      symptom criteria and comprises a primary module, 3 submodules based on the
      predominant symptom pattern (constipation, diarrhea, and pain) and severity
      level, and a subspecialist referral module. CONCLUSIONS: The dearth of available
      evidence highlights the need for more rigorous scientific validation to identify
      the most accurate methods of diagnosing IBS. Until such time, the diagnostic
      algorithm presented herein could inform decision making for a range of providers
      caring for primary care patients with abdominal discomfort or pain and altered
      bowel function suggestive of IBS.

PMID- 11570937
TI  - Cognitive and other adverse effects of diphenhydramine use in hospitalized older
      patients.
AB  - BACKGROUND: Diphenhydramine hydrochloride is a commonly prescribed medicine in
      hospitalized patients, but its adverse effects on older patients remain unclear.
      METHODS: We enrolled 426 hospitalized medical patients aged 70 years or older in
      a prospective cohort study in a university hospital. Measurements included
      baseline and daily assessments including Mini-Mental State Examination scores,
      Confusion Assessment Method ratings, direct observations for medical devices
      (urinary catheter or physical restraints), and blinded medical record extractions
      for diphenhydramine use. RESULTS: Of the 426 patients, 114 (27%) received
      diphenhydramine during hospitalization and shared similar baseline
      characteristics including age, sex, delirium risk, and Mini-Mental State
      Examination scores compared with nonexposed patients. The diphenhydramine-exposed
      group was at an increased risk for any delirium symptoms (relative risk [RR],
      1.7; 95% confidence interval [CI], 1.3-2.3) and for individual delirium symptoms,
      including inattention (RR, 3.0; 95% CI, 1.5-5.9), disorganized speech (RR, 5.5;
      95% CI, 1.0-29.8), and altered consciousness (RR, 3.1; 95% CI, 1.6-6.1). Exposed
      patients also had increased risk for urinary catheter placement (RR, 2.5; 95% CI,
      1.0-6.0) and longer median length of stay (7 vs 6 days; P =.009). A dose-response
      relationship was demonstrated for most adverse outcomes. Overall, 24% of
      diphenhydramine doses were administered inappropriately. CONCLUSIONS:
      Diphenhydramine administration in older hospitalized patients is associated with
      an increased risk of cognitive decline and other adverse effects with a dose
      response relationship. Careful review of its use is necessary in this vulnerable
      population.

PMID- 11570938
TI  - Processes of care, illness severity, and outcomes in the management of community
      acquired pneumonia at academic hospitals.
AB  - BACKGROUND: Prompt antibiotic administration, oxygenation measurement, and blood
      cultures are generally considered markers of high-quality care in the inpatient
      management of community-acquired pneumonia (CAP). However, few studies have
      examined the relationship between prompt achievement of process-of-care markers
      and outcomes for patients with CAP. We examined whether antibiotic administration
      within 8 hours of hospital arrival, a blood culture within 24 hours, an
      oxygenation measurement within 24 hours, or performing blood cultures before
      giving antibiotics was associated with the following: (1) reaching clinical
      stability within 48 hours of hospital admission, (2) a decreased length of
      hospital stay, or (3) fewer inpatient deaths. METHODS: A retrospective medical
      record review identified 1062 eligible patients discharged from the hospital with
      a diagnosis of CAP between December 1, 1997, and February 28, 1998, among 38 US
      academic hospitals. We assessed the independent relationship between each process
      marker and the 3 clinical outcomes, controlling for the Pneumonia Severity Index
      on admission. We also examined the relationship of pneumonia severity on
      admission to process marker achievement and clinical outcomes. RESULTS: Overall,
      there was no consistent or statistically significant relationship between
      achieving process markers and better clinical outcomes (P>.40 for all). We did
      observe that performing blood cultures within 24 hours was related to not
      achieving clinical stability within 48 hours (odds ratio, 1.62; 95% confidence
      interval, 1.13-2.33). However, this finding likely reflects residual confounding
      by severity of illness, since increasing pneumonia severity on admission was
      associated with blood culture performance (P =.009) and with shorter times to
      antibiotic administration (P =.04). CONCLUSIONS: Achieving process-of-care
      markers was not associated with improved outcomes, but was related to the
      severity of pneumonia as assessed on admission. Our results highlight the
      difficulty in demonstrating a link between process-of-care markers and outcomes
      in observational studies of CAP. Randomized studies are needed to objectively
      evaluate the impact of process-of-care markers on CAP outcomes.

PMID- 11570939
TI  - Prevention and treatment of postphlebitic syndrome: results of a 3-part study.
AB  - BACKGROUND: The true incidence of postphlebitic syndrome (PPS) following proximal
      deep venous thrombosis (DVT) and the efficacy of graduated compression stockings
      in preventing and treating PPS are unknown. METHODS: A 3-part study of 202
      patients evaluated 1 year after proximal DVT: 2 randomized placebo-controlled
      trials of stockings and 1 prospective cohort of untreated patients. Patients were
      evaluated for PPS, using a standardized questionnaire, and for venous valvular
      incompetence, using photoplethysmography and venous Doppler. They were enrolled
      in study 1 or study 2 if they did not have symptomatic PPS and did not have or
      had venous valvular incompetence, respectively, and into study 3 if they had
      symptomatic PPS. Study 1 patients were left untreated and followed up for
      development of PPS every 6 months for a mean of 55 months. Study 2 patients were
      randomized to a below-knee stocking (20-30 mm Hg) or a matched placebo stocking,
      and followed up for development of PPS every 6 months for a mean of 57 months.
      Study 3 patients were randomized to an active stocking (30-40 mm Hg) or a matched
      placebo stocking and followed up every 3 months for treatment failure, defined a
      priori. RESULTS: In study 1, 6 (5.0%) of 120 patients were categorized as
      treatment failures, a rate similar to placebo-treated study 2 patients (P =.10).
      In study 2, 0 (0%) of 24 active and 1 (4.3%) of 23 placebo-treated patients were
      categorized as treatment failures (P =.49). In study 3, 11 (61.1%) of 18 active
      and 10 (58.8%) of 17 placebo-treated patients were categorized as treatment
      failures (P>.99). CONCLUSIONS: Most patients do not have PPS 1 year after
      proximal DVT, and do not require stockings. We failed to show a benefit of
      stockings in patients with PPS, but the small numbers preclude definitive
      conclusions.

PMID- 11570940
TI  - Bloodstream infections after invasive nonsurgical cardiologic procedures.
AB  - OBJECTIVE: To define the incidence, risk factors, and characteristics of
      bloodstream infections (BSIs) after invasive nonsurgical cardiologic procedures
      (ICPs). METHODS: Retrospective case-control study; multivariate analysis.
      RESULTS: Between January 1991 and December 1998, 22 006 ICPs were performed in
      our hospital and 25 BSIs were documented within 72 hours after ICP. Overall
      incidence of bacteremia was 0.11% (25 cases) (0.24% after percutaneous
      transluminal coronary angioplasty [14 cases of 5625 patients], 0.06% [corrected]
      after diagnostic cardiac catheterization [9 cases of 14 034 patients], and 0.08%
      [corrected] after electrophysiologic studies [2 cases of 2347 patients]). These
      25 patients with bacteremia were compared with 50 controls randomly selected
      among patients who underwent an ICP but did not have BSIs. Patient-related risk
      factors for BSI were age older than 60 years (20 cases [80%] vs 28 controls
      [56%]), valvular disease (4 [16%] vs 1 [2%]), congestive heart failure (7 [28%]
      vs 1 [2%]), indwelling bladder catheter before the ICP (5 [20%] vs 1 [2%]), more
      than 1 puncture for the ICP (5 [20%] vs 3 [6%]), a prolonged procedure (83.7 vs
      65.1 minutes); and/or more than 1 ICP performed (2 [8%] vs 0). Multivariate
      analysis identified the presence of congestive heart failure (odds ratio, 21; 95%
      confidence interval, 6.8-66.0) and age older than 60 years (odds ratio, 1.9; 95%
      confidence interval, 1.9-6.3) as independent risk factors for BSI after ICP.
      Bloodstream infection was detected a median of 1.7 days after the procedure. Gram
      negative bacteremia accounted for 17 cases (68%) of the BSIs. Among the patients
      with BSI, the duration of hospital stay was significantly increased (21 vs 6
      days). The overall mortality rate was 0.009% for patients who underwent an ICP
      (8.0% for the 25 patients with bacteremia documented within 72 hours after ICP).
      CONCLUSIONS: Bloodstream infection should be included among the potential
      complications of ICP. Elderly patients with recent congestive heart failure
      episodes constitute a subgroup with a higher risk of postprocedure bacteremia.
      Therapy with antimicrobial agents against gram-positive and gram-negative
      bacteremia should be initiated after performing blood cultures in patients with
      signs suggestive of infection.

PMID- 11570942
TI  - Oral anticoagulation and hemorrhagic complications in an elderly population with
      atrial fibrillation.
AB  - BACKGROUND: Warfarin sodium therapy in patients with atrial fibrillation markedly
      reduces the incidence of embolic stroke. However, in elderly patients warfarin
      therapy is often underused owing to the perceived higher risk of hemorrhagic
      complications. OBJECTIVES: To assess the quality of anticoagulant control and the
      incidence of hemorrhagic complications and stroke in an elderly population (>75
      years old) compared with a younger control group (between 60 and 69 years) and to
      assess the quality of anticoagulant control and incidence of hemorrhagic
      complications in those patients who recently commenced receiving warfarin therapy
      (first year of therapy). PATIENTS AND METHODS: In this retrospective follow-up
      study, anticoagulant control and the incidence of hemorrhagic complications and
      stroke were assessed in an elderly population (>75 years old) compared with a
      younger control group (between 60 and 69 years), all with atrial
      fibrillation(target international normalized ratio [INR] 2.5) and attending a
      hospital outpatient anticoagulant clinic. RESULTS: A total of 328 patients were
      studied over a 21-month period. There were 204 patients in the control group
      providing 288 patient-years of follow-up and 124 patients in the elderly group
      providing 170 patient-years of follow-up. The percentage of INR results in the
      target range was not statistically significantly different between the elderly
      and control groups (71.5% vs 66.1%) and the occurrences of incidences of INR
      greater than 7 were 4.2% in the control group and 4.7% in the elderly group (P
      =.96). The incidences of major hemorrhage were 2.8% per year in the elderly group
      and 2.9% per year in the control group (P =.96); overall incidence was 2.8% (95%
      confidence interval, 1.3%-4.4%). One hundred one of the 328 patients studied
      commenced warfarin therapy during or within 3 months of the start of the study.
      In this induction group, 62.1% of INRs were within the target range compared with
      70.9% of INRs in patients who had been receiving warfarin therapy for more than 3
      months at the start of the study (P =.002). The incidences of INR greater than 7
      and major hemorrhage were 7.9% per year and 6.9% per year, respectively, in the
      cohort who recently began warfarin therapy compared with 3.4% per year and 1.7%
      per year in the group who were receiving warfarin therapy for more than 3 months.
      CONCLUSION: While it was impossible to consider any selection bias at the level
      of referral to the clinic, these findings suggest that the elderly population
      attending our anticoagulant clinic did not have poorer anticoagulant control or
      an increased incidence of hemorrhage while receiving warfarin therapy.

PMID- 11570941
TI  - Diagnosis of influenza in the community: relationship of clinical diagnosis to
      confirmed virological, serologic, or molecular detection of influenza.
AB  - BACKGROUND: Successful treatment of influenza depends on an accurate diagnosis of
      the illness and prompt intervention. However, there is a lack of data comparing
      clinical diagnosis vs laboratory diagnostic techniques. OBJECTIVE: To compare the
      clinical diagnosis of community cases of influenza with various laboratory
      diagnostic techniques including multiplex, reverse transcription polymerase chain
      reaction. METHODS: Clinical diagnosis, viral isolation, hemagglutinin inhibition
      serology, and multiplex, reverse transcription polymerase chain reaction were
      used to diagnose influenza in patients enrolled in international phase 3 studies
      designed to investigate the efficacy and safety of an anti-influenza drug
      (inhaled zanamivir). Patients clinically diagnosed with influenza were enrolled
      at centers across North America and Europe. RESULTS: A total of 791 (77%) of 1033
      patients with laboratory results from all 3 methods were confirmed positive for
      influenza by 1 or more test results. For 692 patients (67%), the results of all 3
      tests agreed. Total symptom scores at baseline showed a significant association
      toward greater severity of symptoms with an increasing number of positive test
      results (P<.001). An increasing number of positive test results also showed a
      significant correlation with a longer time to alleviation of symptoms of
      influenza in the placebo group (P =.001). CONCLUSIONS: During a time when
      influenza was known to be circulating and clinical diagnostic criteria were
      applied, diagnosis of influenza in these trials was accurate in approximately 77%
      of adults on clinical grounds alone. This highlights the need for primary care
      physicians to be alerted to circulating influenza and to be aware that
      presentation with cough and fever provide the most predictive symptoms.

PMID- 11570943
TI  - Noninvasive Helicobacter pylori testing for the "test-and-treat" strategy: a
      decision analysis to assess the effect of past infection on test choice.
AB  - BACKGROUND: Clinical guidelines support a noninvasive Helicobacter pylori "test
      and-treat" strategy for individuals with uncomplicated dyspepsia. However,
      consensus is lacking regarding the preferred noninvasive testing method.
      OBJECTIVE: To use decision analytic modeling to estimate the clinical and
      economic outcomes associated with noninvasive tests designed to detect either H
      pylori antibody or active H pylori infection. DESIGN: Decision analytic model.
      PATIENTS: A simulated patient cohort with uncomplicated dyspepsia. INTERVENTIONS:
      The simulated dyspepsia cohort underwent antibody testing or testing to detect
      active H pylori infection (active testing). Individuals testing positive received
      eradication therapy. MAIN OUTCOME MEASURES: Appropriate and inappropriate
      treatment prescribed, cost per patient treated, incremental cost per unnecessary
      treatment avoided. RESULTS: Active testing led to a substantial reduction in
      unnecessary treatment for patients without active infection (antibody, 23.7;
      active, 1.4 per 100 patients) at an incremental cost of $37 per patient. The
      clinical advantage and cost-effectiveness of active testing was enhanced as the
      percentage of individuals with a positive antibody test result from past, but not
      current, infection increased. CONCLUSIONS: Active testing for H pylori infection
      significantly decreases the inappropriate use of antimicrobial therapy when
      compared with antibody testing. The advantages of active testing should be
      enhanced as the widespread use of antimicrobial agents increases the proportion
      of patients with antibody to H pylori, but without active infection.

PMID- 11570944
TI  - Obese patients' perceptions of treatment outcomes and the factors that influence
      them.
AB  - BACKGROUND: Despite considerable professional consensus that modest weight losses
      of 5% to 10% are successful for reducing the comorbid conditions associated with
      obesity, obese patients often desire weight losses 2 to 3 times greater than
      this. Examining ways to reduce the disparities between treatment expectations and
      subsequent outcomes, this study evaluated the role of physical characteristics,
      treatment setting, and mood in patients' evaluations of treatment outcomes.
      METHODS: This study was conducted in a university outpatient weight loss clinic
      with a sample of 397 obese individuals seeking weight loss by a variety of
      modalities. Before treatment, participants' heights and weights were measured,
      and the Beck Depression Inventory and the Goals and Relative Weight Questionnaire
      were administered. RESULTS: Outcome evaluations ranged from 64.4 +/- 11.1 kg
      (mean +/- SD) for dream weight to 90.1 +/- 19.1 kg for disappointed weight.
      Initial body weight was the strongest predictor of disappointed, acceptable, and
      happy weights (beta =.90,.76, and.57, respectively). Sex (beta = -.37) and height
      (beta =.37) were the strongest determinants of dream weight. Heavier participants
      chose higher absolute weights, but the weight loss required to reach each of the
      outcomes was greater for heavier than for lighter patients. CONCLUSIONS: These
      data signal a therapeutic dilemma in which the amount of weight loss produced by
      the best behavioral and/or pharmacologic treatments is viewed as even less than
      disappointing. Patients with the highest pretreatment weights are likely to have
      the most unrealistic expectations for success.

PMID- 11570945
TI  - Recurrent pneumococcal bacteremia: risk factors and outcomes.
AB  - BACKGROUND: Recurrent pneumococcal bacteremia receives infrequent mention in the
      literature, usually in association with patients who are immunocompromised.
      OBJECTIVE: To examine recurrent cases of pneumococcal bacteremia to determine
      risk factors and outcomes (mortality rates and emergence of resistance)
      associated with recurrences. METHODS: We retrospectively reviewed all cases of
      pneumococcal bacteremia identified by our microbiology laboratory from January 1,
      1992, through December 31, 1996. Demographic, clinical, and laboratory data were
      abstracted. RESULTS: There were 462 bacteremic episodes in 432 patients; 23 of
      these patients had 30 recurrent episodes. The 5.3% recurrence rate (23/432) is
      greater than that previously described. The median time to recurrence was 200
      days. The mean age of patients with recurrences was 34 years, 70% were women, all
      were black or Hispanic (in near equal numbers), and 87% were infected with the
      human immunodeficiency virus (HIV). Human immunodeficiency virus infection,
      coexistent cancer, and female sex were independent predictors of recurrence. Only
      patients who were HIV-infected had multiple recurrences. Isolates from recurrent
      bacteremias were more likely to be penicillin-resistant than were initial
      bacteremic isolates (relative risk, 2.0; P =.16). Patients with recurrences had a
      higher (although not statistically significant) mortality rate than those without
      recurrences (22% vs 16%; P =.33). There was an inverse relationship between
      severity of illness and likelihood of recurrence. CONCLUSIONS: Rates of recurrent
      pneumococcal bacteremia may be higher than previously reported. In patients with
      recurrent pneumococcal bacteremia, the presence of an underlying immunodeficiency
      should be investigated.

PMID- 11570946
TI  - Severe orthostatic hypotension following weight reduction surgery.
AB  - Surgical interventions for morbid obesity are common practice in many countries,
      especially when other treatment options have failed or when rapid weight loss is
      desired. The association between weight and blood pressure is well established,
      especially the paradigm of obesity-related hypertension. We describe a 45-year
      old obese woman with a medical history of hypertension and type 2 diabetes
      mellitus who lost 57 kg within a few months after a weight reduction surgery. She
      suffered from severe orthostatic hypotension, which probably resulted from
      sympathetic nervous system dysfunction. Our patient's clinical status improved
      with pharmacological interventions, but her symptoms resolved completely after
      she gained weight following a surgical reversal of the gastric partitioning owing
      to a local complication. Autonomic nervous system activity does change with the
      changes in body weight, but after evaluation of this patient, we believe that
      rapid weight loss may impair sympathetic function and blood pressure control.
      Although losing weight is a known treatment option for hypertension, exaggerated
      reversal of obesity-related hypertension might result in orthostatic hypotension.

PMID- 11570947
TI  - Does anticoagulant treatment reduce the mortality of acute pulmonary embolism?

PMID- 11570948
TI  - Sarcoidosis-associated bronchiolitis obliterans organizing pneumonia.

PMID- 11570949
TI  - Blood coagulation disorders during primary cytomegalovirus infection.

PMID- 11570950
TI  - Clinical research requires IRB review.

PMID- 11570951
TI  - The role of thiazide diuretics in preventing ischemic stroke.

PMID- 11570952
TI  - Differences between primary vs secondary prevention trials regarding the stroke
      protective effect of antihypertensive drugs.

PMID- 11570954
TI  - Clinical and ethical concerns about switching patient treatment to
      "therapeutically interchangeable" medications.

PMID- 11570956
TI  - Oxidative stress, DNA damage and the Y chromosome.
AB  - Recent advances in understanding of male infertility have implicated two major
      causative factors, oxidative stress and Y chromosome deletions. A major cause of
      oxidative stress appears to be the high rate of reactive oxygen species
      generation associated with the retention of excess residual cytoplasm in the
      sperm midpiece. Other possible causes include the redox cycling of xenobiotics,
      and antioxidant depletion or apoptosis. Oxidative stress induces peroxidative
      damage in the sperm plasma membrane and DNA damage in both the mitochondrial and
      nuclear genomes. Nuclear DNA damage in the germ line of the father may be
      associated with pathology in the offspring, including childhood cancer and
      infertility. Gene deletions on the non-recombining region of the Y chromosome
      account for the infertility observed in about 15% of patients with azoospermia
      and 5-10% of subjects with severe oligozoospermia. The Y chromosome is
      particularly susceptible to gene deletions because of the inability of the
      haploid genome to deploy recombination repair in retrieving lost genetic
      information. Aberrant recombination, defective chromatin packaging, abortive
      apoptosis and oxidative stress may all be involved in the aetiology of DNA damage
      in the germ line. The factors responsible for Y chromosome deletions in
      spermatozoa remain unresolved but may be one facet of a central reproductive
      problem: controlling the amount of oxidative stress experienced by germ cells
      during their differentiation and maturation in the male reproductive tract.

PMID- 11570957
TI  - Developmental consequences of embryo and cell manipulation in mice and farm
      animals.
AB  - Advances in biotechnology in recent decades have revolutionized our understanding
      of early mammalian development and promise to provide ever more finely tuned and
      precisely targeted techniques for genetic enhancement of domestic animal species.
      In demonstrating what is both technically and biologically possible, not only in
      mice but also in larger animal species, research has provided hope that
      previously intractable diseases and genetic defects can be successfully combated.
      Crucial to this research is the ability to culture oocytes, embryos and somatic
      cells in vitro and to sustain their development without inducing adverse short-
      or long-term consequences. There is a need to refine current culture strategies
      in farm animal species to avoid jeopardizing their dependent technologies. A key
      to resolving current limitations of culture strategies is to identify,
      acknowledge and then address those features of in vitro culture that compromise
      early regulation of mammalian development. The aim of this review is to appraise
      critically in vitro embryo and somatic cell production strategies in the context
      of their impact on developmental competence and normality at embryonic, fetal and
      later stages. In addition, effects of physically manipulating embryos and cells,
      most notably via nuclear and gene transfer technologies, are considered with a
      view to identifying how detrimental consequences can be avoided.

PMID- 11570958
TI  - Hyperactivation of mammalian spermatozoa: function and regulation.
AB  - Hyperactivation is a movement pattern observed in spermatozoa at the site and
      time of fertilization in mammals. It may be critical to the success of
      fertilization, because it enhances the ability of spermatozoa to detach from the
      wall of the oviduct, to move around in the labyrinthine lumen of the oviduct, to
      penetrate mucous substances and, finally, to penetrate the zona pellucida of the
      oocyte. The movement of hyperactivated spermatozoa appears different under
      different physical conditions and in different species, but basically it involves
      an increase in flagellar bend amplitude and beat asymmetry. Presumably, there is
      a signal or signals in the oviduct to initiate hyperactivation at the appropriate
      time; however, none has yet been identified. There is evidence that the source of
      the signal is follicular fluid, yet spermatozoa are known to hyperactivate before
      ovulation would release the fluid into the oviduct. Although the signal
      transduction cascade regulating hyperactivation remains to be described
      completely, it is clear that calcium ions interact with the axoneme of the
      flagellum to switch on hyperactivation. The process may also involve increases in
      intracellular cAMP, which at least is required to support motility in general.
      Although hyperactivation usually occurs during capacitation, the two events are
      regulated by different pathways.

PMID- 11570959
TI  - Micronutrient programming of development throughout gestation.
AB  - Vitamins and minerals serve essential roles in cellular metabolism, maintenance
      and growth throughout life. They are also central components of many enzymes and
      transcription factors. However, the need for optimum amounts of key
      micronutrients at critical stages during the periovulatory period and subsequent
      embryonic and fetal life has become the focus of sustained research activity only
      recently. In addition to folic acid, the minerals zinc, iron and copper and the
      antioxidant vitamins A and E are of particular importance during pregnancy. Both
      excesses and deficiencies of these micronutrients can have profound and sometimes
      persistent effects on many fetal tissues and organs in the absence of clinical
      signs of deficiency in the mother. The consequences of micronutrient imbalance on
      the developing conceptus may not be apparent at the time of the nutritional
      insult, but may be manifest later in development. However, supplementary
      micronutrients provided later in gestation or during postnatal life cannot
      completely reverse the detrimental effects of earlier micronutrient imbalance.
      Importantly, deficiency of a specific micronutrient, such as zinc, during
      pregnancy can result in a greater incidence of fetal malformation and resorptions
      than general undernutrition. Given the range of micronutrients that affect
      development, the number of developmental stages susceptible to inappropriate
      micronutrient status and the diverse biochemical systems and types of tissue
      affected, it is challenging to propose a unifying hypothesis that could explain
      the effects of micronutrient imbalance on programming throughout gestation.
      Micronutrient imbalance can affect pregnancy outcome through alterations in
      maternal and conceptus metabolism, as a consequence of their essential role in
      enzymes and transcription factors and through their involvement in signal
      transduction pathways that regulate development. Micronutrient-induced
      disturbances in the balance between the generation of free oxygen radicals and
      the production of antioxidants that scavenge free radicals may provide an
      additional mechanistic explanation. The detrimental effects of many micronutrient
      deficiencies, particularly zinc and copper, can be alleviated by supplementary
      antioxidants, whereas deficiencies of antioxidant vitamins A and E are likely to
      reduce defence against free radical damage.

PMID- 11570960
TI  - Growth hormone and fertility in oMt1a-oGH transgenic mice.
AB  - Female mice carrying a regulatable growth hormone transgene (oMt1a-oGH) are
      subfertile when the transgene is actively expressed. This study was designed to
      characterize subfertility caused by increased concentrations of growth hormone.
      In particular, this study aimed to: (i) determine the effects of transgene
      activation and inactivation on mating, conception, maintenance of pregnancy,
      ovulation rate, litter characteristics and embryonic survival at day 17 of
      pregnancy, (ii) characterize oestrous cyclicity in transgenic versus wild-type
      female mice, and (iii) correlate corticosterone concentrations with transgene
      expression and reproductive performance. Transgenic and wild-type female mice
      were allocated randomly to one of four treatment groups at weaning: (i)
      transgenic female mice that always express the transgene, (ii) transgenic female
      mice that never express the transgene, (iii) transgenic female mice that express
      the transgene for up to 8 weeks of age and (iv) non-transgenic wild-type female
      mice receiving the transgene stimulus until 8 weeks of age. Activation followed
      by inactivation of the transgene resulted in an increased incidence of remating,
      resulting in an extended interval to establish pregnancy in comparison with all
      other treatment groups. Transgenic mice that always expressed the transgene and
      those that expressed the transgene for up to 8 weeks of age had lower pregnancy
      rates and higher ovulation rates compared with mice from other treatment groups.
      Both embryonic survival and the duration of the oestrous cycle did not differ
      among treatment groups. Active expression of the transgene resulted in an
      increase in the plasma concentration of corticosterone, which was associated with
      reduced fertility. These data indicate that the presence of a high growth hormone
      concentration impedes the establishment and maintenance of pregnancy. Increased
      plasma corticosterone concentrations may interfere with implantation as well as
      potentiate leptin resistance, which has been reported previously in studies with
      these mice.

PMID- 11570961
TI  - Temperature dependence of intracellular Ca2+ homeostasis in rat meiotic and
      postmeiotic spermatogenic cells.
AB  - The hypothesis that intracellular [Ca2+] is a cell parameter responsive to
      extreme temperatures in rat meiotic and postmeiotic spermatogenic cells was
      tested using intracellular fluorescent probes for Ca2+ and pH. In agreement with
      this hypothesis, extreme temperatures induced a rapid increase of cytosolic
      [Ca2+] in rat pachytene spermatocytes and round spermatids. Oscillatory changes
      in temperature can induce oscillations in cytosolic [Ca2+] in these cells.
      Intracellular [Ca2+] homeostasis in round spermatids was more sensitive to high
      temperatures compared with pachytene spermatocytes. The calculated activation
      energies for SERCA ATPase-mediated fluxes in pachytene spermatocytes and round
      spermatids were 62 and 75 kJ mol(-1), respectively. The activation energies for
      leak fluxes from intracellular Ca2+ stores were 55 and 68 kJ mol(-1) for
      pachytene spermatocytes and round spermatids, respectively. Together with changes
      in cytosolic [Ca2+], round spermatids undergo a decrease in pH(i) at high
      temperatures. This temperature-induced decrease in pH(i) appears to be partially
      responsible for the increase in cytosolic [Ca2+] of round spermatids induced by
      high temperatures. This characteristic of rat meiotic and postmeiotic
      spermatogenic cells to undergo an increment in cytosolic Ca2+ at temperatures >
      33 degrees C can be related to the induction of programmed cell death by high
      temperatures in these cells.

PMID- 11570962
TI  - Expression of prostaglandin D synthetase during development in the mouse testis.
AB  - Prostaglandin D synthetase is expressed relatively highly in the testis and
      reproductive tract of a number of species, including the mouse. In adult mouse
      testis, expression is confined largely to the Leydig cells and in this study
      changes in the expression and localization of prostaglandin D synthetase mRNA
      during testis development were examined. Initial studies using RT-PCR and
      isolated testicular compartments indicated that prostaglandin D synthetase
      expression in the neonatal testis was predominantly within the seminiferous
      tubules. In situ hybridization studies confirmed that prostaglandin D synthetase
      mRNA appears to be expressed only in the tubules of neonatal mouse testes and
      only in the interstitial tissue of the adult testis. TaqMan real-time PCR was
      used to quantify prostaglandin D synthetase mRNA content during development using
      an exogenous mRNA as a control standard. Expression per testis decreased after
      birth to < 10% at day 15 before recovering again by days 25-30. After day 30,
      expression per testis increased 40-fold during final development to adulthood.
      Studies using RT-PCR showed that early expression before day 15 was restricted to
      the tubular compartment, whereas the subsequent increase in expression after day
      30 was restricted to the interstitial compartment. Database analysis showed that
      the 3' end of the prostaglandin D synthetase transcript was subject to alternate
      splicing. Both splice isoforms were shown by RT-PCR to be present throughout
      development and without a major change in expression pattern. These results
      indicate that expression of prostaglandin D synthetase mRNA shifts during
      development from the tubular compartment of the fetal or neonatal testis to the
      developing adult Leydig cells, with expression in the Leydig cells increasing
      markedly after puberty. These changes are similar to those observed for 17beta
      hydroxysteroid dehydrogenase type III and may indicate that this developmental
      process is not uncommon in the testis.

PMID- 11570963
TI  - Gonadotrophin responsiveness, aromatase activity and insulin-like growth factor
      binding protein content of bovine ovarian follicles during the first follicular
      wave.
AB  - The aim of this study was to examine the function of granulosa cells and hormone
      concentrations in follicular fluid in bovine ovarian follicles during selection
      of the first dominant follicle. Ovaries were obtained from beef heifers on days 1
      5 after ovulation: follicles > 4 mm in diameter were dissected and follicular
      fluid and granulosa cells were collected from individual follicles. Oestradiol
      production by granulosa cells after culture with testosterone was used to
      determine aromatase activity and responsiveness to gonadotrophins was determined
      by cAMP production after culture with FSH or LH. Concentrations of oestradiol,
      progesterone and insulin-like growth factor binding proteins (IGFBPs)-4 and -5
      were measured in follicular fluid. Follicles were classified as largest or
      smaller (days 1 and 2), or dominant or subordinate (days 3-5). Aromatase activity
      was greater in granulosa cells from the largest follicle than in granulosa cells
      from smaller follicles on days 1, 3, 4 and 5 (P < 0.05). Responsiveness to LH was
      not detected in granulosa cells on day 1, but from day 2 to day 5 cells from the
      largest follicle were significantly more responsive than cells from smaller
      follicles (P < 0.05). Responsiveness to FSH was detected in granulosa cells from
      all follicles from day 1 onwards and did not differ between cells from the
      largest follicle or smaller follicles on any day. Follicular fluid concentrations
      of oestradiol and the ratio of oestradiol:progesterone were greater and
      concentrations of IGFBP-4 and -5 were lower in the largest follicle than in
      smaller follicles from day 2 to day 5 (P < 0.05). In conclusion, selection of the
      dominant follicle is associated with increased granulosa cell aromatase activity
      followed by increased cAMP response to LH and follicular fluid oestradiol
      concentrations, and decreased follicular fluid concentrations of IGFBP-4 and -5
      within 2 days after ovulation.

PMID- 11570964
TI  - Hormonal characterization of the reproductive cycle and pregnancy in the female
      Mohor gazelle (Gazella dama mhorr).
AB  - The oestrous cycles of seven captive Mohor Gazelles (Gazella dama mhorr) were
      investigated. Hormone profiles obtained from faecal samples collected each day
      from cyclic females indicated that the mean duration of the oestrous cycle was
      18.62 +/- 0.26 days (range 16-22 days; n = 37 oestrous cycles). No inter
      individual differences in the concentration of faecal progestagen metabolites
      excreted were observed, but mean faecal oestrogen excretion during both the
      luteal and inter-luteal phases of the oestrous cycle varied among females (P <
      0.001 and P = 0.070, respectively). Oestrous cycles were synchronized using
      controlled internal drug release (CIDR) devices, before natural mating with an
      intact male. Concentrations of faecal progestagen metabolites remained
      approximately constant for the first 10 weeks of gestation (mean +/- SEM = 4048
      +/- 407 ng g(-1) faeces), before increasing to a mean of 23 556 +/- 1176 ng g(-1)
      faeces. Two of seven female gazelles conceived immediately after removal of the
      CIDR device, a similar proportion to that conceived at the postpartum oestrus
      under natural conditions. Life history data for these individuals indicated that
      the mean time to conception in female gazelles is positively correlated with peak
      values in the ratio of excreted oestrogen : progestagen during the inter-luteal
      period of their oestrous cycles (R(2) = 0.58; P < 0.05). This finding indicates
      that interactions between steroid production and metabolism may influence the
      likelihood of conception occurring in this species.

PMID- 11570965
TI  - An in situ hybridization study of the effects of artificial insemination on the
      localization of cells expressing MHC class II mRNA in the chicken oviduct.
AB  - The aim of this study was to determine the effects of artificial insemination on
      the localization of antigen-presenting cells expressing MHC class II mRNA in
      chicken oviducts. Laying hens (35 weeks old) were inseminated with fresh semen or
      sham-inseminated with saline daily for 3 days. In situ hybridization was
      performed to detect chicken MHC class II (B-LB21 major gene) mRNA on frozen
      sections of oviductal infundibulum, uterovaginal junction and vagina by using
      digoxigenin-labelled PCR probes. Cells expressing MHC class II were observed
      mainly in the oviductal mucosal stroma and occasionally in the mucosal
      epithelium. After 24 h, the population of cells expressing MHC class II in the
      infundibulum was significantly higher in laying hens inseminated with fresh semen
      than in the control hens sham-inseminated with saline (P < 0.05). However, there
      was no significant difference in the population of cells expressing MHC class II
      in the uterovaginal junction and vagina between the artificially inseminated and
      control hens. These results indicate that anti-sperm immune responses, including
      the influx of cells expressing MHC class II and enhanced MHC class II mRNA
      expression, probably occur in the infundibulum after artificial insemination.

PMID- 11570966
TI  - Benefit of FSH priming of women with PCOS to the in vitro maturation procedure
      and the outcome: a randomized prospective study.
AB  - The aim of this study was to determine whether the rates of in vitro oocyte
      maturation, fertilization and cleavage, as well as implantation rate and
      pregnancy rate, could be improved by low-dose priming with FSH in vivo before
      retrieval of immature oocytes in patients with polycystic ovary syndrome (PCOS).
      From March 1998 to June 2000, a total of 28 women underwent 36 completed
      treatment cycles, randomized sequentially in one of two groups. Women in group 1
      (n = 12 cycles) received no stimulation and women in group 2 (n = 24 cycles)
      received 150 iu recombinant FSH day(-1) for 3 days, initiated on day 3 after
      menstruation. Aspiration was performed transvaginally between day 9 and day 17 in
      the unstimulated group and on day 8 or day 9 in the FSH-primed group after FSH
      deprivation for 2 or 3 days. All cumulus-enclosed oocytes of healthy appearance
      were matured in culture medium (TCM-199) in vitro for 28-36 h before
      intracytoplasmic sperm injection (ICSI). After oocyte retrieval the women were
      given oestradiol (6 mg day(-1)) and progesterone administration (300 mg day(-1))
      was initiated 2 days later. Suitable embryos (maximum two embryos) were
      transferred on day 3 after ICSI. The percentage of oocytes reaching metaphase II
      was significantly higher (P < 0.05) in the FSH-primed group (59%, 92/156)
      compared with the non-primed group (44%, 36/81). There were no significant
      differences in the rates of oocyte fertilization and cleavage between these
      groups. No pregnancies were obtained in group 1 (0%, 0/12), whereas seven
      clinical pregnancies were obtained in group 2 (29%, 7/24) (P < 0.05). In group 2,
      37 embryo transfers resulted in eight implantations (21.6%). Three healthy
      singleton children have been born at term; the remaining pregnancies ended with
      spontaneous abortions in the first trimester. These results indicate that priming
      with recombinant FSH before harvesting of immature oocytes from patients with
      PCOS may improve the maturational potential of the oocytes and the implantation
      rate of the cleaved embryos.

PMID- 11570967
TI  - Cloning of rat interleukin 11 and interleukin 11 receptor alpha chain and
      analysis of their expression in rat uterus in the peri-implantation period.
AB  - Studies in mice have shown that interleukin 11 (IL-11) signalling is required for
      female fertility. In the absence of IL-11, decidualization is markedly retarded
      and implantation fails. IL-11 acts via a heterodimeric receptor composed of a
      ligand-specific receptor alpha chain (IL-11R alpha) and the signalling moiety
      gp130. This study reports the cloning of genes encoding rat IL-11 and IL-11R
      alpha. RNase protection was used to demonstrate that expression of IL-11 is
      upregulated in the rat uterus at the initiation of implantation at 5.5 days after
      mating. Expression of the genes encoding the two receptor components, IL11Ra and
      gp130, did not change throughout the peri-implantation period. In situ
      hybridization studies revealed that, as in mice, expression of IL-11 was high in
      the primary decidual zone at the time of the attachment reaction, whereas IL11Ra
      was expressed throughout primary and secondary decidua. Conservation of the
      temporal and spatial expression of IL-11 and IL-11R alpha in the uterus of the
      mouse and rat during the peri-implantation period will facilitate future studies
      investigating the role of IL-11 in fertility.

PMID- 11570968
TI  - Changes in the relative abundance of mRNA transcripts for insulin-like growth
      factor (IGF-I and IGF-II) ligands and their receptors (IGF-IR/IGF-IIR) in
      preimplantation bovine embryos derived from different in vitro systems.
AB  - The aim of this study was to determine the relative abundance of mRNAs for the
      insulin-like growth factor I (IGF-I) and IGF-II ligands, and for the IGF
      receptors (IGF-IR and IGF-IIR) in in vitro preimplantation bovine embryos from
      the oocyte to the hatched blastocyst stage using two different culture systems:
      TCM-199 supplemented with oestrous cow serum, or synthetic oviduct fluid
      supplemented with polyvinyl alcohol. Development to the two- to four-cell stage
      and blastocyst stage was significantly higher (P < or = 0.05) in embryos cultured
      in TCM supplemented with oestrous cow serum than in those cultured in synthetic
      oviduct fluid supplemented with polyvinyl alcohol (61 and 25% versus 55 and 17%,
      respectively). A semi-quantitative RT-PCR assay did not detect IGF-I transcripts
      at any stage of preimplantation bovine development, including the hatched
      blastocyst stage. In both culture systems, IGF-IR, IGF-II and IGF-IIR were
      expressed throughout preimplantation development up to the hatched blastocyst
      stage in a varying pattern. The expression patterns of IGF-IR, IGF-II and IGF-IIR
      in embryos generated in the two culture systems were not significantly different,
      except at the expanded blastocyst stage, at which significantly higher amounts of
      IGF-IIR were observed in the TCM system than in the synthetic oviduct fluid
      system. These results indicate that transcripts of IGF-IR and IGF-IIR follow the
      standard pattern in which maternal stores of mRNA in the oocyte are slowly
      depleted up to the 16-cell stage and then re-established at the onset of
      embryonic expression of these genes. The lack of detectable IGF-I transcripts in
      the bovine embryo indicates a predominantly paracrine mode of action. The bovine
      embryo is capable of producing IGF-II, IGF-IIR and IGF-IR in large amounts,
      particularly after hatching, which may be important for the formation of the
      filamentous conceptus. Results indicate an autocrine mechanism for IGF-II and
      modulation of IGF family expression by culture conditions.

PMID- 11570970
TI  - Pale vacuolated epithelial cells in epididymis of aflatoxin-treated mice.
AB  - The responses of the mouse epididymal epithelium to subchronic doses of aflatoxin
      B1 were investigated in a histological study. Either few and large or small and
      profuse vacuoles containing an amorphous to dense periodic acid-Schiff-positive
      material were observed in the epithelium of all the segments of the epididymis.
      Resin-embedded semi-thin sections and transmission electron microscopy indicated
      that these vacuoles were intracellular. The cells that contained these vacuoles
      were quite different in organization and electron density from the cell types
      already established in the epididymal epithelium and are designated as pale
      vacuolated epithelial cells. Owing to aflatoxin B1 toxicity, the apical membrane
      of some of the principal cells, either individually or in groups, disintegrated
      so that the principal cells released their contents into the lumen of the duct
      through development of a 'fistula'. Spermatozoa from the ductal lumen entered the
      principal cell fistula and reached the basal lamina. If extravasation of the
      spermatozoa via this route occurred, it would bring about an autoimmune response,
      leading to the formation of spermatic granulomas and the generation of anti-sperm
      antibodies. Extravasation of spermatozoa seems to be offset by the underlying
      basal cell, which is presumed to develop into a pale vacuolated epithelial cell
      to enclose the disintegrating principal cells and the spermatozoa arriving at the
      principal cell. Thus, the development of pale vacuolated epithelial cells may be
      a protective device preventing an autoimmune response to sperm antigens in the
      context of toxicant-induced degeneration of the principal cells of the epididymal
      epithelium.

PMID- 11570971
TI  - Delayed effect of low progesterone concentrations on bovine uterine PGF(2alpha)
      secretion in the subsequent oestrous cycle.
AB  - Low progesterone concentrations during the bovine oestrous cycle induce enhanced
      responsiveness to oxytocin challenge late in the luteal phase of the same cycle.
      The delayed effect of low progesterone concentrations during one oestrous cycle
      on uterine PGF(2alpha) secretion after oxytocin challenge on day 15 or 16 of the
      subsequent cycle was studied by measuring the concentrations of the major
      PGF(2alpha) metabolite (13,14-dihydro-15-keto PGF(2alpha); PGFM) in plasma. Two
      experiments were conducted, differing in the type of progesterone treatment and
      in the shape of the low progesterone concentration curves. In Expt 1,
      progesterone supplementation with intravaginal progesterone inserts, with or
      without an active corpus luteum, was used to obtain high, or low and constant
      plasma progesterone concentrations, respectively. In Expt 2, untreated cows,
      representing high progesterone treatment, were compared with cows that had low
      but increasing plasma progesterone concentrations that were achieved by
      manipulating endogenous progesterone secretion of the corpus luteum. Neither
      experiment revealed any differences in plasma progesterone concentrations between
      the high and low progesterone groups in the subsequent oestrous cycle. In both
      experiments, both groups had similar basal concentrations of PGFM on day 15 (Expt
      1) or 16 (Expt 2) of the subsequent oestrous cycle, 18 days after progesterone
      treatments had ended. In both experiments, the increases in PGFM concentrations
      in the low progesterone groups after an oxytocin challenge were markedly higher
      than in the high progesterone groups. These results indicate that low
      progesterone concentrations during an oestrous cycle have a delayed stimulatory
      effect on uterine responsiveness to oxytocin during the late luteal phase of the
      subsequent cycle. This resulting increase in PGF(2alpha) secretion may interfere
      with luteal maintenance during the early stages of pregnancy.

PMID- 11570969
TI  - Involvement of connexin 43 in meiotic maturation of bovine oocytes.
AB  - In ovarian follicles, cumulus cells provide the oocyte with small molecules that
      permit growth and control maturation. These nutrients reach the germinal cell
      through gap junction channels, which are present between the cumulus cells and
      the oocyte, and between the cumulus cells. In this study the involvement of
      intercellular communication mediated by gap junction channels on oocyte
      maturation of in vitro cultured bovine cumulus-oocyte complexes (COCs) was
      investigated. The stages of oocyte maturation were determined by Hoechst 33342
      staining, which showed that 90% of COCs placed in the maturation medium for 24 h
      progress to the metaphase II stage. Bovine COC gap junction communication was
      disrupted initially using n-alkanols, which inhibit any passage through gap
      junctions. In the presence of 1-heptanol (3 mmol l(-1)) or octanol (3.0 mmol l(
      1) and 0.3 mmol l(-1)), only 29% of the COCs reached metaphase II. Removal of the
      uncoupling agent was associated with restoration of oocyte maturation, indicating
      that treatment with n-alkanols was neither cytotoxic nor irreversible.
      Concentrations of connexin 43 (Cx43), the major gap junction protein expressed in
      the COCs, were decreased specifically using a recombinant adenovirus expressing
      the antisense Cx43 cDNA (Ad-asCx43). The efficacy of adenoviral infection was >
      95% in cumulus cells evaluated after infection with recombinant adenoviruses
      expressing the green fluorescence protein. RT-PCR performed on total RNA isolated
      from Ad-asCx43-infected COCs showed that the rat Cx43 cDNA was transcribed.
      Western blot analysis revealed a three-fold decrease in Cx43 expression in COCs
      expressing the antisense RNA for Cx43. Injection of cumulus cells with Lucifer
      yellow demonstrated further that the resulting lower amount of Cx43 in infected
      COCs is associated with a two-fold decrease in the extent of coupling between
      cumulus cells. In addition, oocyte maturation was decreased by 50% in the
      infected COC cultures. These results indicate that Cx43-mediated communication
      between cumulus cells plays a crucial role in maturation of bovine oocytes.

PMID- 11570972
TI  - Inhibition of mouse fertilization in vivo by intra-oviductal injection of an anti
      equatorin monoclonal antibody.
AB  - The monoclonal antibody mMN9 recognizes an antigenic molecule, equatorin, which
      is localized at the equatorial segment of the mammalian sperm acrosome. Our
      previous results using an IVF system indicated that mMN9 blocked sperm-oocyte
      fusion. Antibody-containing and control solutions were injected directly into the
      right and left oviductal ampullae, respectively, of anaesthetized female mice to
      assess the effect of mMN9 on fertilization in vivo. After hCG treatment, the
      females were mated, and their oviductal eggs and implanted embryos were examined.
      mMN9 was retained in the oviductal lumen at 20 h after injection. The rates of
      fertilization and concomitant pregnancy were significantly lower than in the
      control side (P < 0.05). In addition, histological studies showed no evidence of
      pathological changes in the female reproductive tract after the injections. These
      results indicate that mMN9 inhibits mouse fertilization significantly under in
      vivo conditions and that this injection method should be useful for studying the
      effects of antibodies and agents on fertilization in vivo.

PMID- 11570973
TI  - Measurement of apoptosis in long-term cultures of human ovarian tissue.
AB  - At present, the long-term culture of ovarian tissue is problematic. The aim of
      this study was to measure apoptosis in long-term cultures of human ovarian
      tissue. Biopsies of human ovaries were cultured for 6 weeks. Samples were taken
      weekly for histological investigation. The apoptotic cells were marked with anti
      caspase 3. Simultaneous to this experiment, other tissue samples were
      preincubated for 3 h with 1 micromol staurosporine l(-1), an inducer of
      apoptosis, and apoptosis was compared among samples. Furthermore, the proportion
      of lethal cells was determined weekly. After 6 weeks, 99% of the tissue samples
      showed an intact structure. They expanded in all directions on the floor of the
      multi-wells to form a monolayer. Apoptotic cells could be marked only
      sporadically (16.3 +/- 5.9 fluorescence (counts per 3600 microm(2))) after 6
      weeks. After preincubation with staurosporine after the same period of culture,
      the proportion of apoptotic cells was significantly increased compared with that
      in untreated control samples (66.8 +/- 14.5 versus 16.3 +/- 5.9%, respectively; P
      < 0.05). Under the same experimental conditions, the proportion of lethal cells
      was 3.6 +/- 0.9, 3.9 +/- 2.1 and 5.2 +/- 1.5% for weeks 1, 3 and 6, respectively.
      After preincubation with 1 micromol staurosporine l(-1), the proportion of
      pyknotic cells after 6 weeks of culture was significantly higher (37.2 +/- 4.4%)
      than that in control samples (3.95 +/- 2.05%; P < 0.05). No significant increase
      in apoptosis in cultured human ovarian tissue after 6 weeks was observed compared
      with control tissues on day 1. These results indicate that under optimal culture
      conditions it is possible to cultivate human ovarian tissue long term. The
      influence of long-term culture on hormone synthesis and follicle maturity will be
      investigated further.

PMID- 11570974
TI  - amiA is a negative regulator of acetamidase expression in Mycobacterium
      smegmatis.
AB  - BACKGROUND: The acetamidase of Mycobacterium smegmatis is a highly inducible
      enzyme. Expression of this enzyme is increased 100-fold when the substrate
      acetamide is present. The acetamidase gene is found immediately downstream of
      three open reading frames. Two of these are proposed to be involved in
      regulation. RESULTS: We constructed a deletion mutant in one of the upstream ORFs
      (amiA). This mutant (Mad1) showed a constitutively high level of acetamidase
      expression. We identified four promoters in the upstream region using a beta
      galactosidase reporter gene. One of these (P2) was inducible in the wild-type,
      but was constitutively active in Mad1. CONCLUSIONS: These results demonstrate
      that amiA encodes a negative regulatory protein which interacts with P2. Since
      amiA has homology to DNA-binding proteins, it is likely that it exerts the
      regulatory effect by binding to the promoter to prevent transcription.

PMID- 11570975
TI  - Itt1p, a novel protein inhibiting translation termination in Saccharomyces
      cerevisiae.
AB  - BACKGROUND: Termination of translation in eukaryotes is controlled by two
      interacting polypeptide chain release factors, eRFl and eRF3. eRFl recognizes
      nonsense codons UAA, UAG and UGA, while eRF3 stimulates polypeptide release from
      the ribosome in a GTP- and eRFl - dependent manner. Recent studies has shown that
      proteins interacting with these release factors can modulate the efficiency of
      nonsense codon readthrough. RESULTS: We have isolated a nonessential yeast gene,
      which causes suppression of nonsense mutations, being in a multicopy state. This
      gene encodes a protein designated Itt1p, possessing a zinc finger domain
      characteristic of the TRIAD proteins of higher eukaryotes. Overexpression of
      Itt1p decreases the efficiency of translation termination, resulting in the
      readthrough of all three types of nonsense codons. Itt1p interacts in vitro with
      both eRFl and eRF3. Overexpression of eRFl, but not of eRF3, abolishes the
      nonsense suppressor effect of overexpressed Itt1p. CONCLUSIONS: The data obtained
      demonstrate that Itt1p can modulate the efficiency of translation termination in
      yeast. This protein possesses a zinc finger domain characteristic of the TRIAD
      proteins of higher eukaryotes, and this is a first observation of such protein
      being involved in translation.

PMID- 11570976
TI  - Is it Crohn's disease? A severe systemic granulomatous reaction to sulfasalazine
      in patient with rheumatoid arthritis.
AB  - BACKGROUND: Sulfasalazine is a widely used anti-inflammatory agent in the
      treatment of inflammatory bowel disease and several rheumatological disorders.
      Although as many as 20% of treated patients may experience reversible, dose
      dependent side effects, less frequent but potentially severe, systemic reactions
      have also been reported. CASE PRESENTATION: A severe systemic reaction to
      sulfasalazine developed in a 21-year old female with rheumatoid arthritis
      characterized by eosinophilia, granulomatous enteritis and myelotoxicity,
      cholestatic hepatitis, and seizures. The clinical course and management of this
      patient are presented as well as a review of the incidence and outcome of severe
      systemic reactions to sulfasalazine. CONCLUSIONS: Granulomatous myelotoxicity and
      enteritis developed in a 21 year old female within 3 weeks of initiating
      sulfasalazine for rheumatoid arthritis. Following a short course of
      corticosteroids, the patient had resolution of her cholestatic hepatitis, rash,
      eosinophilia, and gastrointestinal symptoms with no residual manifestations at 7
      months follow-up. Although severe reactions to sulfasalazine are rare and
      unpredictable, practicing physicians should be aware of unusual clinical
      presentations of toxicity when prescribing sulfasalazine.

PMID- 11570977
TI  - Electrolytic ablation of the rat pancreas: a feasibility trial.
AB  - BACKGROUND: Pancreatic cancer is a biologically aggressive disease with less than
      20% of patients suitable for a "curative" surgical resection. This, combined with
      the poor 5-year survival indicates that effective palliative methods for symptom
      relief are required. Currently there are no ablative techniques to treat
      pancreatic cancer in clinical use. Tissue electrolysis is the delivery of a
      direct current between an anode and cathode to induce localised necrosis.
      Electrolysis has been shown to be safe and reliable in producing hepatic tissue
      and tumour ablation in animal models and in a limited number of patients. This
      study investigates the feasibility of using electrolysis to produce localised
      pancreatic necrosis in a healthy rat model. METHOD: Ten rats were studied in
      total. Eight rats were treated with variable "doses" of coulombs, and the
      systemic and local effects were assessed; 2 rats were used as controls. RESULTS:
      Seven rats tolerated the procedure well without morbidity or mortality, and one
      died immediately post procedure. One control rat died on induction of
      anaesthesia. Serum amylase and glucose were not significantly affected.
      CONCLUSION: Electrolysis in the rat pancreas produced localised necrosis and
      appears both safe, and reproducible. This novel technique could offer significant
      advantages for patients with unresectable pancreatic tumours. The next stage of
      the study is to assess pancreatic electrolysis in a pig model, prior to human
      pilot studies.

PMID- 11570978
TI  - The G-308A variant of the Tumor Necrosis Factor-alpha (TNF-alpha) gene is not
      associated with obesity, insulin resistance and body fat distribution.
AB  - BACKGROUND: Tumor Necrosis Factor-alpha (TNF-alpha) has been implicated in the
      pathogenesis of insulin resistance and obesity. The increased expression of TNF
      alpha in adipose tissue has been shown to induce insulin resistance, and a
      polymorphism at position -308 in the promoter region ofTNF-alpha has been shown
      to increase transcription of the gene in adipocytes. Aim of this study is to
      investigate the role of the G-308A TNFalpha variant in obesity and to study the
      possible influence of this mutation on body fat distribution and on measures of
      obesity (including Fat Free Mass, Fat Mass, basal metabolic rate), insulin
      resistance (measured as HOMAIR), and lipid abnormalities. The G-308A TNFalpha
      polymorphism has been studied in 115 patients with obesity (mean BMI 33.9 +/-
      0.5) and in 79 normal lean subjects (mean BMI 24.3 +/- 0.3). METHODS: The G-308A
      variant, detected by PCR amplification and Nco-1 digestion, determines the loss
      of a restriction site resulting in a single band of 107 bp [the (A) allele].
      RESULTS: The (A) allele frequencies of the G-308A TNFalpha polymorphism were
      13.1% in the obese group and 14.6% in the lean subjects, with no significant
      difference between the two groups. Furthermore, no association was found with BMI
      classes, body fat distribution, HOMAIR, and metabolic abnormalities. CONCLUSIONS:
      Our study did not detect any significant association of the G-308A TNFalpha
      polymorphism with obesity or with its clinical and metabolic abnormalities in
      this population. Our data suggests that, in our population, the G-308A TNFalpha
      polymorphism is unlikely to play a major role in the pathogenesis of these
      conditions.

PMID- 11570979
TI  - Abduction paresis with rostral pontine and/or mesencephalic lesions:
      Pseudoabducens palsy and its relation to the so-called posterior internuclear
      ophthalmoplegia of Lutz.
AB  - BACKGROUND: The existence of a prenuclear abduction paresis is still debated.
      METHODS: In a retrospective design, we identified 22 patients with isolated
      unilateral (n = 20) or bilateral (n = 2) abduction paresis and electrophysiologic
      abnormalities indicating rostral pontine and/or mesencephalic lesions. Another 11
      patients had unilateral abduction paresis with additional ocular motor
      abnormalities indicating midbrain dysfunction. Eight of these 11 patients also
      had electrophysiological abnormalities supporting this location.
      Electrophysiological examinations in all patients included masseter and blink
      reflexes (MassR, BlinkR), brainstem auditory evoked potentials (BAEP), and direct
      current elctro-oculography (EOG). RESULTS: Unilateral MassR abnormalities in
      patients with unilateral abduction paresis were seen in 17 patients and were
      almost always (in 16 of 17 patients) on the side of the abduction paresis.
      Another 11 patients had bilateral MassR abnormalities. BlinkR was always normal.
      EOG disclosed slowed abduction saccades in the non-paretic eye in 6 patients and
      slowed saccades to the side opposite to the abduction paresis in another 5
      patients. Re-examinations were done in 27 patients showing normalization or
      improvement of masseter reflex abnormalities in 18 of 20 patients and in all
      patients with EOG abnormalities. This was always associated with clinical
      improvement. CONCLUSIONS: Electrophysiologically documented or clinically evident
      rostral pontine and/or mesencephalic lesions in our patients exclude an
      infranuclear intrapontine 6th nerve lesion and indicate the existence of an
      abduction paresis of prenuclear origin. An increased tone of the antagonistic
      medial rectus muscle during lateral gaze either by abnormal convergence or
      impaired medial rectus inhibition seems most likely.

PMID- 11570980
TI  - A mathematical model of optimized radioiodine-131 therapy of Graves'
      hyperthyroidism.
AB  - BACKGROUND: The current status of radioiodine-131 (RaI) dosimetry for Graves'
      hyperthyroidism is not clear. Recurrent hyperthyroidism and iatrogenic
      hypothyroidism are two problems which interact such that trying to solve one
      leads to exacerbation of the other. Optimized RaI therapy has therefore begun to
      be defined just in terms of early hypothyroidism (ablative therapy) as physicians
      have given up on reducing hypothyroidism. METHODS: Optimized therapy is evaluated
      both in terms of the greatest separation of cure rate from hypothyroidism rate
      (non-ablative therapy) or in terms of early hypothyroidism (ablative therapy) by
      mathematical modeling of outcome after radioiodine and critically discussing the
      three common methods of RaI dosing for Graves' disease. RESULTS: Cure follows a
      logarithmic relationship to activity administered or absorbed dose, while
      hypothyroidism follows a linear relationship. The effect of including or omitting
      factors in the calculation of the administered I-131 activity such as the
      measured thyroid uptake and effective half-life of RaI or giving extra
      compensation for gland size is discussed. CONCLUSIONS: Very little benefit can be
      gained by employing complicated methods of RaI dose selection for non-ablative
      therapy since the standard activity model shows the best potential for cure and
      prolonged euthyroidism. For ablative therapy, a standard MBq/g dosing provides
      the best outcome in terms of cure and early hypothyroidism.

PMID- 11570981
TI  - Lack of correlation between Ki-67 labelling index and tumor size of anterior
      pituitary adenomas.
AB  - AIMS AND BACKGROUND: The Ki-67 is a nuclear antigen detected by the monoclonal
      antibody MIB-1 and its Labeling Index (LI) is considered a marker of normal and
      abnormal cell proliferation. Pituitary adenomas are generally well differentiated
      neoplasms, even if in about one third of cases they are invasive of surrounding
      tissues. The aim of this study is to evaluate the correlation between Ki-67
      labelling index and tumor size of pituitary adenomas extimated by means CT and
      MRI and confirmed at operation. METHODS: Using the monoclonal antibody MIB-1, we
      evaluated the expression of Ki-67 in 121 anterior pituitary adenomas
      consecutively operated on in a 48-month period. RESULTS: In relation to
      neuroradiological (CT and MRI) and surgically verified tumor size, we identified
      24 microadenomas, 27 intrasellar macroadenomas, 34 intra-suprasellar
      macroadenomas, and 36 intra-supra-parasellar macroadenomas. The adenomas were non
      infiltrating (76 cases) and infiltrating (45 cases) adenomas. The wall of the
      cavernous sinus (CS) was infiltrated in 18 cases. Forty-eight adenomas were non
      functioning and 73 functioning. The overall mean +/- SD Ki-67 LI was 2.72 +/-
      2.49% (median 1.6). It was 2.59 +/- 1.81 in microadenomas, 2.63 +/- 3.45 in
      intrasellar macroadenomas, 1.91 +/- 2.11 in intra-suprasellar macroadenomas, and
      3.29 +/- 5.45 in intra-supra-parasellar macroadenomas (p = 0.27). It was 3.73 +/-
      5.13% in infiltrating and 2.03 +/- 2.41% in non-infiltrating adenomas (p = 0.02),
      and 5.61 +/- 7.19% in CS-infiltrating versus 2.09 +/- 2.37% in CS-non
      infiltrating adenomas (p = 0.0005). CONCLUSIONS: Our preliminary results seem to
      exclude significative correlations between Ki-67 LI and tumor size of anterior
      pituitary adenomas, even if this index can be considered a useful marker in the
      determination of the infiltrative behaviour of these tumors.

PMID- 11570982
TI  - The effect of EGTA and Ca++ in regulation of the brain Na/K-ATPase by
      noradrenaline.
AB  - BACKGROUND: The Na/K-ATPase activity of the brain synaptic plasma membranes (SPM)
      is regulated by noradrenaline (NA) and the synaptosomal factor SF (soluble
      protein obtained from the synaptosome cytosol). In the absence of SF, NA inhibits
      Na/K-ATPase, while, on addition of SF to the reaction medium, there is a NA
      dependent activation of Na/K-ATPase. On the other hand, EGTA augments the Na/K
      ATPase activity and attenuates the ability of NA to inhibit Na/K-ATPase. RESULTS:
      Considering that Ca2+ ion is a Na/K-ATPase modifier, it can be assumed that the
      effect of NA and SF is a Ca2+-dependent process. However, in the presence of 0.3
      mM EGTA and 0.1 mM NA, the apparent inhibition constant for Ca2+ (at [Ca2+] > 0.3
      mM) is not SF dependent, while the apparent activation constant for SF does not
      change at increasing Ca2+ concentration ([Ca2+] < 0.3 mM). At various Ca2+
      concentrations (0.06, 0.35 and 0.6 mM), no significant changes occur in the mode
      of action of NA on the Na/K-ATPase activity in the presence of 5 microg/ml SF.
      EGTA also has no effect on the NA-independent activation of Na/K-ATPase evoked by
      high SF concentrations. CONCLUSIONS: Taking into account that in the absence of
      EGTA similar results have been obtained, it can be concluded that the effect of
      NA and SF on brain Na/K-ATPase is a Ca2+-independent process.

PMID- 11570983
TI  - Nutrition and cognitive impairment in the elderly.
AB  - As the number of older people is growing rapidly worldwide and the fact that
      elderly people are also apparently living longer, dementia, the most common cause
      of cognitive impairment is getting to be a greater public health problem.
      Nutrition plays a role in the ageing process, but there is still a lack of
      knowledge about nutrition-related risk factors in cognitive impairment. Research
      in this area has been intensive during the last decade, and results indicate that
      subclinical deficiency in essential nutrients (antioxidants such as vitamins C, E
      and beta-carotene, vitamin B(12), vitamin B(6), folate) and nutrition-related
      disorders, as hypercholesterolaemia, hypertriacylglycerolaemia, hypertension, and
      diabetes could be some of the nutrition-related risk factors, which can be
      present for a long time before cognitive impairment becomes evident. Large-scale
      clinical trials in high-risk populations are needed to determine whether lowering
      blood homocysteine levels reduces the risk of cognitive impairment and may delay
      the clinical onset of dementia and perhaps of Alzheimer's disease. A curative
      treatment of cognitive impairment, especially Alzheimer's disease, is currently
      impossible. Actual drug therapy, if started early enough, may slow down the
      progression of the disease. Longitudinal studies are required in order to
      establish the possible link of nutrient intake--nutritional status with cognitive
      impairment, and if it is possible, in fact, to inhibit or delay the onset of
      dementia.

PMID- 11570984
TI  - The erythrocyte incorporation of absorbed non-haem iron in pregnant women.
AB  - Studies of Fe absorption in pregnancy often make unfounded assumptions of
      erythrocyte incorporation. Therefore, we measured the absorption and utilisation
      of Fe during early and late pregnancy by the erythrocyte incorporation of two
      stable isotopes. 8.5 mg 57Fe (oral) and 0.5 mg (58)Fe (intravenous) were given to
      five non-pregnant women, to five women in early gestation (12 weeks) and five
      women in late gestation (36 weeks). The stable isotope ratios in whole blood 14 d
      later were measured by MS. Together with estimation of body Fe mass, this enabled
      the calculation of Fe absorption and erythrocyte incorporation. In non-pregnant
      women, Fe absorption averaged 20.3 (range 10.2-34.3) %. It was not significantly
      different in early pregnancy (11.8 (range, 4.4-24.8) %), but during late
      pregnancy Fe absorption increased to 59.0 (range 38.2-77.2) %. All non-pregnant
      and early-pregnancy subjects had normal Fe status, but two women in late
      pregnancy had evidence of Fe insufficiency. During early and late pregnancy, mean
      erythrocyte incorporation was 63.4 (SD 12.1) % and 71.0 (SD 10.4) % respectively,
      significantly reduced compared with non-pregnant subjects (90.1 (SD 6.0) %).
      Decreased erythrocyte incorporation of absorbed Fe in early pregnancy is
      compatible with reduced Fe demand and low oral absorption. However, during late
      pregnancy decreased erythrocyte incorporation associated with high absorption and
      Fe insufficiency is different from the high erythrocyte incorporation which
      occurs in non-pregnant Fe-deficient women. This suggests that part of the
      aetiology of Fe deficiency during pregnancy may be the reduction of Fe
      utilisation.

PMID- 11570985
TI  - Comparison of non-tracer and tracer methods for determination of volatile fatty
      acid production rate in the rumen of sheep fed on two levels of intake.
AB  - The aim of the present work was to estimate volatile fatty acid (VFA) production
      rate in the rumen of sheep fed two levels of intake using both a tracer (TM; by
      isotope dilution) and a non-tracer method (NTM; by supplementary infusion) in
      steady-state conditions. Six wethers received a diet containing 700 g lucerne hay
      and 300 g ground maize/kg in eight equal meals at 3 h intervals per d. The diet
      (9.8 MJ metabolizable energy (ME)/kg DM) was offered at 90 % ad libitum
      consumption (high intake, HI) or 45 % ad libitum consumption (low intake, LI) in
      a crossover design. Each sheep received five intrarumen VFA solutions infused
      continuously for 24 h at rates of 250 ml and 165 ml/h for the HI and LI
      respectively. The first infusion, considered as a control treatment (Con),
      consisted of a solution of [1-(13)C]propionate (7 mmol/d). The four other
      solutions were isoenergetic (1.9 MJ ME/kg DM intake) mixtures of unlabelled
      propionate (C(3)) and butyrate (C(4)) at different levels: 0.90 mol C(4)/kg DM
      intake; 0.60 mol C(3)/kg DM intake; 0.30 mol C(3)/kg DM intake; 1.35 mol C(3)/kg
      DM intake. The VFA infusions did not affect rumen fermentation of the basal diet
      (pH, osmotic pressure, protozoa numbers), and comparable DM digestibility of the
      diet among the different treatments was observed. Both estimation methods
      demonstrated a similar increase (1.7-fold) in the rumen VFA production rate of
      sheep fed at intakes varying between 0.9 to 1.7 times maintenance. Irrespective
      of the intake level, the rumen production rate of individual VFA was on average
      1.5-fold higher when estimated by the TM compared with the NTM. Rumen VFA
      production rates estimated by the NTM and TM represented 80 % and 120 % ME intake
      respectively. The difference between NTM and TM estimates seems likely to be
      caused mainly by overestimation of the VFA production rates by the TM.

PMID- 11570986
TI  - The prebiotic effects of biscuits containing partially hydrolysed guar gum and
      fructo-oligosaccharides--a human volunteer study.
AB  - Prebiotics are non-digestible food ingredients that target selected groups of the
      human colonic microflora, thus having the ability to alter the composition
      towards a more 'beneficial' community, i.e. selectively increasing populations of
      bifidobacteria and/or lactobacilli. In the present study the prebiotic potential
      of partially hydrolysed guar gum (PHGG) and fructo-oligosaccharides (FOS) in a
      biscuit was assessed in human volunteers. Fluorescent in situ hybridization using
      oligonucleotide probes targeting Bacteroides spp., Bifidobacterium spp.,
      Clostridium spp. and Lactobacillus-Enterococcus spp. were used for the
      bacteriology and total bacteria were enumerated using the fluorescent stain 4',6
      diamidino-2-phenylindole. Thirty-one volunteers consumed daily either three
      experimental biscuits (providing a total (g/d) of 6.6 FOS and 3.4 PHGG) or three
      placebo biscuits for two 21-d crossover periods. Bifidobacteria significantly
      increased in number on ingestion of the experimental biscuits compared with pre
      treatment and placebo population levels. Bifidobacterial numbers returned to
      pretreatment levels within 7 d of the cessation of intake of experimental
      biscuits. A correlation was observed between the initial faecal bifidobacterial
      numbers and the magnitude of bifidogenesis, with volunteers who possessed low
      initial population levels of bifidobacteria experiencing the greatest increase in
      bifidogenesis. No changes were observed in the other bacterial groups monitored
      during the trial. Thus, the prebiotic nature of FOS and PHGG was maintained in a
      final food product as evidenced from the selective increase in bifidobacterial
      numbers.

PMID- 11570987
TI  - Effects of dietary oleic-rich oils (virgin olive and high-oleic-acid sunflower)
      on vascular reactivity in Wistar-Kyoto and spontaneously hypertensive rats.
AB  - The effects of two monounsaturated fatty acid (MUFA)-rich diets, containing
      virgin olive oil (OO) and high-oleic-acid sunflower oil (HOSO), on development of
      vascular response from isolated thoracic rat aorta and lipid composition and
      fatty acid composition were studied and compared with samples from rats fed on a
      control diet. Dietary MUFA oils were fed for 6 weeks to spontaneously
      hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 weeks of age. The maximum
      contraction of aortic ring preparations in response to phenylephrine (10(-6) m)
      was significantly decreased in SHR rats fed with OO (0.81 (sem 0.05) v. 1.18 (sem
      0.09) g, and treatment with HOSO did not alter the phenylephrine-induced
      contractions. The relaxant responses to acetylcholine (10(-5) m) were
      significantly enhanced (30.03 (sem 0.70) v. 18.47 (sem 0.28) %, in the rings from
      SHR rats treated with OO, and were more pronounced than in WKY rats In the same
      way, OO attenuated the dose-response curves induced by phenylephrine (10(-8)-10(
      5) m) from SHR rats, accompanied with a slower contraction. These results suggest
      that only the chronic feeding of OO diet was able to attenuate the vascular
      response of rat aorta. In addition, an increase in phospholipid content (186.7
      (sd 3.2) v. 159.1 (sd 11.3) g/kg, and changes in the fatty acid composition of
      aorta (mainly a decrease in arachidonic acid) could contribute to improving
      endothelial function. Therefore, the effects can not be attributed exclusively to
      the content of MUFA (mainly oleic acid). Other components of OO, such as
      polyphenols, not present in HOSO, may help to explain the vascular protective
      effect of OO consumption.

PMID- 11570988
TI  - A dynamic model to analyse intravenous glucose and insulin tolerance tests
      performed on dairy cows.
AB  - A dynamic model was developed to assess insulin sensitivity and pancreatic
      response in lactating dairy cows. The model is based on a simultaneous analysis
      of insulin and glucose intravenous tolerance tests. It comprises five
      compartments corresponding to insulin in portal-hepatic plasma, and insulin or
      glucose in both systemic plasma and in interstitial fluid. Insulin secretion rate
      is a sigmoidal function of glucose in plasma. Insulin is cleared from hepatic
      plasma and from the interstitial fluid. The glucose entry rate is constant and
      glucose utilization rate is a sigmoidal function of insulin in the interstitial
      fluid. Six parameters were estimated: two for insulin secretion rate, two for
      insulin clearance, one for glucose entry rate and one for glucose utilization
      rate. After integration of the functions, the model yielded a relative estimate
      of the quantities of insulin secreted and cleared, as well as the glucose
      entering and utilized during each test. Using an experimental dataset composed of
      ten pairs of tolerance tests, the explained variations for plasma insulin and
      glucose concentrations were 96.0 and 98.3 % and standard errors of estimates were
      0.032 nmol/l and 0.14 mmol/l respectively. Except in the early stages after
      injection, residual errors were low. A Jackknife analysis showed that the
      estimated parameters exhibited low statistical bias. This model simplifies the
      interpretation of both tests through a simulation based on six common parameters.
      Compared to a classical analysis of tolerance tests, it may improve the analysis
      of modifications in the key functions regulating glucose homeostasis in
      ruminants.

PMID- 11570989
TI  - Polyunsaturated fatty acid-rich diets: effect on adipose tissue metabolism in
      rats.
AB  - The aim of the present study was to evaluate the effect of diets rich in n-6 and
      n-3 fatty acids on adipose tissue metabolism. Starting at weaning, male Wistar
      rats were fed ad libitum, for 8 weeks with one of the following diets: C, rat
      chow; S, rat chow containing 15 % (w/w) soyabean oil; F, rat chow containing 15 %
      (w/w) fish oil; SF, rat chow containing 15 % (w/w) soyabean and fish oil (5:1,
      w/w). Casein was added to the fat diets to achieve the same 20 % (w/w) protein
      content as in the control chow. Food intake and body weight were measured weekly.
      The rats were killed by decapitation and the retroperitoneal (RET) and epididymal
      (EPI) white adipose tissues were removed and weighed. Tissue lipid and protein
      content, in vivo lipogenesis rate, uptake of diet-derived lipids, in vitro
      lipolytic rate, adipocyte area, lipoprotein lipase, ATP citrate lyase, and malic
      enzyme activities were evaluated. Carcass lipid and protein contents were also
      measured. Energy intake was reduced while carcass lipid content was increased in
      the three fat-fed groups. However, carcass protein and body weight gains were
      elevated only with diets F and SF. Lipolysis rate was diminished by diets F and
      SF, while the uptake of diet-derived lipids was elevated by the diet S in both
      RET and EPI tissues. These metabolic alterations may have contributed to the
      increase in in vivo lipogenesis rate in the presence of decreased ATP citrate
      lyase and malic enzyme activities induced by the three lipid diets. These results
      indicate that enrichment of the diet with polyunsaturated fatty acids causes
      changes in adipose tissue metabolism that favour fat deposition. Different
      metabolic pathways were preferentially affected by each type of fatty acid used.

PMID- 11570990
TI  - Content of short-chain fatty acids in the hindgut of rats fed processed bean
      (Phaseolus vulgaris) flours varying in distribution and content of indigestible
      carbohydrates.
AB  - Red kidney beans (Phaseolus vulgaris) processed to differ in distribution and
      content of indigestible carbohydrates were used to study hindgut fermentability
      and production of short-chain fatty acids (SCFA). Bean flours with low or high
      content of resistant starch (RS), mainly raw and physically-inaccessible starch,
      were obtained by milling the beans before or after boiling. Flours containing
      retrograded starch and with a high or low content of oligosaccharides were
      prepared by autoclaving followed by freeze-drying with or without the boiling
      water. Six diets were prepared from these flours yielding a total concentration
      of indigestible carbohydrates of 90 or 120 g/kg (dry weight basis). The total
      fermentability of the indigestible carbohydrates was high with all diets (80-87
      %). Raw and physically-inaccessible starch was more readily fermented than
      retrograded starch (97-99 % v. 86-95 %; ). Non-starch glucans were fermented to a
      lesser extent than RS, but the fermentability was higher in the case of
      autoclaved (50-54 %) than boiled beans (37-41 %). The distribution between
      acetic, propionic and butyric acid in the caecum was similar for all diets, with
      a comparatively high percentage of butyric acid (approximately 18). However, with
      diets containing the high amounts of RS, the butyric acid concentration was
      significantly higher in the distal colon than in the proximal colon ( and for the
      high- and low-level diets respectively), whereas it remained constant, or
      decreased along the colon in the case of the other diets. Furthermore, the two
      diets richest in RS also promoted the highest percentages of butyric acid in the
      distal colon (24 and 17 v. 12 and 12-16 for the high- and low-level diets
      respectively).

PMID- 11570991
TI  - Daily dietary intake of chromium in southern Spain measured with duplicate diet
      sampling.
AB  - We measured daily dietary Cr intake in southern Spain by sampling duplicate diets
      for seven consecutive days in different population groups. Cr was determined by
      electrothermal atomization-atomic absorption spectrometry. The samples were
      mineralized in a digestion block with HNO(3), HClO(4) and V(2)O(5). A total of
      161 duplicate diets from twenty-three subjects were analysed, and mean levels of
      Cr intake ranged from 9.39 to 205.16 microg/d. Mean Cr intake (100 microg/d) was
      similar to levels found for most other countries, and was within the range
      recommended by the National Research Council for a safe and adequate daily intake
      (50-200 microg/d). Chromium intake correlated significantly with energy, protein
      and carbohydrate intake, and with the daily intake of Zn, Fe, Mg, K, Na, Ca and
      nicotinic acid in the diets analysed.

PMID- 11570992
TI  - Markers of high fish intake are associated with decreased risk of a first
      myocardial infarction.
AB  - High intake of fish has been associated with reduced risk of CHD. The high
      content of n-3 polyunsaturated fatty acids (PUFA) in fish has been suggested to
      be a protective factor. In addition, fish is the entirely dominating source of
      methylmercury for the general population, and the concentration of Hg in
      erythrocytes (Ery-Hg) is often used as an index of fish consumption. Our aim was
      to study the relationships between a first-ever myocardial infarction, Ery-Hg,
      activity of gluthathione peroxidase in erythrocytes (Ery-GSH-Px) and plasma
      concentration of the n-3 PUFA eicosapentaenoic and docosahexaenoic acids (P
      PUFA). In a population-based prospective nested case-control study within
      Northern Sweden seventy-eight cases of a first-ever myocardial infarction were
      compared with 156 controls with respect to Ery-Hg, P-PUFA and Ery-GSH-Px. Both
      Ery-Hg and P-PUFA, but not Ery-GSH-Px, were significantly higher in subjects
      reporting high fish intake (at least one meal per week) than in those with lower
      intake. This finding suggests that Ery-Hg and P-PUFA reflect previous long-term
      fish intake. Low risk of myocardial infarction was associated with high Ery-Hg or
      high P-PUFA. In a multivariate model the risk of myocardial infarction was
      further reduced in subjects with both high Ery-Hg and high P-PUFA (odds ratio
      0.16, 95 % CI 0.04, 0.65). In conclusion, there is a strong inverse association
      between the risk of a first myocardial infarction and the biomarkers of fish
      intake, Ery-Hg and P-PUFA, and this association is independent of traditional
      risk factors.

PMID- 11570993
TI  - Dietary assessment in Whitehall II: comparison of 7 d diet diary and food
      frequency questionnaire and validity against biomarkers.
AB  - The aim of the present cross-sectional study was to examine the agreement and
      disagreement between a 7 d diet diary (7DD) and a self-administered machine
      readable food-frequency questionnaire (FFQ) asking about diet in the previous
      year, and to validate both methods with biomarkers of nutrient intake. The
      subjects were an age- and employment-grade-stratified random subsample of London
      based civil servants (457 men and 403 women), aged 39-61 years, who completed
      both a 7DD and a FFQ at phase 3 follow-up (1991-1993) of the Whitehall II study.
      Mean daily intakes of dietary energy, total fat, saturated, monounsaturated and
      polyunsaturated fatty acids, linoleic acid, total carbohydrate excluding fibre,
      sugars, starch, dietary fibre, protein, vitamin C, vitamin E (as alpha-tocopherol
      equivalents), folate, carotenes (as total beta-carotene activity), Fe, Ca, Mg, K
      and alcohol were measured. Serum cholesteryl ester fatty acids (CEFA), plasma
      alpha-tocopherol and beta-carotene were also measured as biomarkers. Estimates of
      mean energy intake from the two methods were similar in men, and some 10 % higher
      according to the FFQ in women. Compared with the 7DD, the FFQ tended to
      overestimate plant-derived micronutrient intakes (carotenes from FFQ v. 7DD men
      2713 (SD 1455) v. 2180 (SD 1188) microg/d, women 3100 (SD 1656) v. 2221 (SD 1180)
      microg/d, both differences P<0.0001) and to underestimate fat intake. Against
      plasma beta-carotene/cholesterol, carotene intake was as well estimated by the
      FFQ as the 7DD (Spearman rank correlations, men 0.32 v. 0.30, women 0.27 v. 0.22,
      all P< or =0.0001, energy-adjusted data). Ranking of participants by other
      nutrient intakes tended to be of the same order according to the two dietary
      methods, e.g. rank correlations for CEFA linoleic acid against FFQ and 7DD
      estimates respectively, men 0.38 v. 0.41, women 0.53 v. 0.62, all P< or =0.0001,
      energy-adjusted % fat). For alpha-tocopherol there were no correlations between
      plasma level and estimated intakes by either dietary method. Quartile agreement
      for energy-adjusted nutrient intakes between the two self-report methods was in
      the range 37-50 % for men and 32-44 % for women, and for alcohol, 57 % in both
      sexes. Disagreement (misclassification into extreme quartiles of intake) was in
      the range 0-6 % for both sexes. The dietary methods yielded similar prevalences
      (about 34 %) of low energy reporters. The two methods show satisfactory
      agreement, together with an expected level of systematic differences, in their
      estimates of nutrient intake. Against the available biomarkers, the machine
      readable FFQ performed well in comparison with the manually coded 7DD in this
      study population. For both methods, regression-based adjustment of nutrient
      intake to mean dietary energy intake by gender appears on balance to be the
      optimal approach to data presentation and analysis, in view of the complex
      problem of low energy reporting.

PMID- 11570994
TI  - Soya intake and plasma concentrations of daidzein and genistein: validity of
      dietary assessment among eighty British women (Oxford arm of the European
      Prospective Investigation into Cancer and Nutrition).
AB  - Soya products contain high levels of the isoflavones genistein and daidzein, and
      their glucosides, and may lower the risk of cardiovascular disease, osteoporosis
      and cancer. The present cross-sectional study investigated plasma concentrations
      of daidzein and genistein and their correlations with dietary soya consumption in
      four groups of twenty premenopausal British women. The women were selected from
      the Oxford arm of the European Prospective Investigation into Cancer and
      Nutrition using data from food-frequency questionnaires (FFQ) to guarantee a wide
      variation in soya consumption, and to investigate the utility of the question
      related to soya milk consumption compared with the utility of the question
      related to other soya foods. Dietary intakes of isoflavones were additionally
      assessed by 7 d food diaries. Plasma concentrations of daidzein and genistein
      were measured by time-resolved fluoroimmunoassay. Geometric mean plasma
      concentrations (nmol/l) were for the four groups, which were based on increasing
      soya intake, 4.9, 8.4, 39.2 and 132 for daidzein and 14.3, 16.5, 119 and 378 for
      genistein. The Spearman correlation coefficients for plasma isoflavone
      concentrations with estimated dietary intakes were between 0.66 and 0.80 for the
      diary-based estimates and between 0.24 and 0.74 for the FFQ-based estimates. The
      correlations for soya milk intakes were clearly higher than the correlations for
      intakes of other soya foods. We conclude that both the food diary and the FFQ
      estimate dietary soya isoflavone intakes sufficiently well to use them in
      epidemiological studies, and that plasma concentrations of daidzein and genistein
      in Western women who consumed soya products as a part of their regular diet were
      close to those in Asian populations.

PMID- 11570995
TI  - Correctness of belief propagation in Gaussian graphical models of arbitrary
      topology.
AB  - Graphical models, such as Bayesian networks and Markov random fields, represent
      statistical dependencies of variables by a graph. Local "belief propagation"
      rules of the sort proposed by Pearl (1988) are guaranteed to converge to the
      correct posterior probabilities in singly connected graphs. Recently, good
      performance has been obtained by using these same rules on graphs with loops, a
      method we refer to as loopy belief propagation. Perhaps the most dramatic
      instance is the near Shannon-limit performance of "Turbo codes," whose decoding
      algorithm is equivalent to loopy propagation. Except for the case of graphs with
      a single loop, there has been little theoretical understanding of loopy
      propagation. Here we analyze belief propagation in networks with arbitrary
      topologies when the nodes in the graph describe jointly gaussian random
      variables. We give an analytical formula relating the true posterior
      probabilities with those calculated using loopy propagation. We give sufficient
      conditions for convergence and show that when belief propagation converges, it
      gives the correct posterior means for all graph topologies, not just networks
      with a single loop. These results motivate using the powerful belief propagation
      algorithm in a broader class of networks and help clarify the empirical
      performance results.

PMID- 11570996
TI  - Mosaic model for sensorimotor learning and control.
AB  - Humans demonstrate a remarkable ability to generate accurate and appropriate
      motor behavior under many different and often uncertain environmental conditions.
      We previously proposed a new modular architecture, the modular selection and
      identification for control (MOSAIC) model, for motor learning and control based
      on multiple pairs of forward (predictor) and inverse (controller) models. The
      architecture simultaneously learns the multiple inverse models necessary for
      control as well as how to select the set of inverse models appropriate for a
      given environment. It combines both feedforward and feedback sensorimotor
      information so that the controllers can be selected both prior to movement and
      subsequently during movement. This article extends and evaluates the MOSAIC
      architecture in the following respects. The learning in the architecture was
      implemented by both the original gradient-descent method and the expectation
      maximization (EM) algorithm. Unlike gradient descent, the newly derived EM
      algorithm is robust to the initial starting conditions and learning parameters.
      Second, simulations of an object manipulation task prove that the architecture
      can learn to manipulate multiple objects and switch between them appropriately.
      Moreover, after learning, the model shows generalization to novel objects whose
      dynamics lie within the polyhedra of already learned dynamics. Finally, when each
      of the dynamics is associated with a particular object shape, the model is able
      to select the appropriate controller before movement execution. When presented
      with a novel shape-dynamic pairing, inappropriate activation of modules is
      observed followed by on-line correction.

PMID- 11570997
TI  - Spike-timing-dependent Hebbian plasticity as temporal difference learning.
AB  - A spike-timing-dependent Hebbian mechanism governs the plasticity of recurrent
      excitatory synapses in the neocortex: synapses that are activated a few
      milliseconds before a postsynaptic spike are potentiated, while those that are
      activated a few milliseconds after are depressed. We show that such a mechanism
      can implement a form of temporal difference learning for prediction of input
      sequences. Using a biophysical model of a cortical neuron, we show that a
      temporal difference rule used in conjunction with dendritic backpropagating
      action potentials reproduces the temporally asymmetric window of Hebbian
      plasticity observed physio-logically. Furthermore, the size and shape of the
      window vary with the distance of the synapse from the soma. Using a simple
      example, we show how a spike-timing-based temporal difference learning rule can
      allow a network of neocortical neurons to predict an input a few milliseconds
      before the input's expected arrival.

PMID- 11570998
TI  - Analysis and neuronal modeling of the nonlinear characteristics of a local
      cardiac reflex in the rat.
AB  - Previous experimental results have suggested the existence of a local cardiac
      reflex in the rat. In this study, the putative role of such a local reflex in
      cardiovascular regulation is quantitatively analyzed. A model for the local
      reflex is developed from anatomical experimental results and physiological data
      in the literature. Using this model, a systems-level analysis is conducted.
      Simulation results indicate that the neuromodulatory mechanism of the local
      reflex attenuates the nonlinearity of the relationship between cardiac vagal
      drive and arterial pressure. This behavior is characterized through coherence
      analysis. Furthermore, the modulation of phase-related characteristics of the
      cardiovascular system is suggested as a plausible mechanism for the nonlinear
      attenuation. Based on these results, it is plausible that the functional role of
      the local reflex is highly robust nonlinear compensation at the heart, which
      results in less complex dynamics in other parts of the reflex.

PMID- 11570999
TI  - Evaluating auditory performance limits: i. one-parameter discrimination using a
      computational model for the auditory nerve.
AB  - A method for calculating psychophysical performance limits based on stochastic
      neural responses is introduced and compared to previous analytical methods for
      evaluating auditory discrimination of tone frequency and level. The method uses
      signal detection theory and a computational model for a population of auditory
      nerve (AN) fiber responses. The use of computational models allows predictions to
      be made over a wider parameter range and with more complete descriptions of AN
      responses than in analytical models. Performance based on AN discharge times (all
      information) is compared to performance based only on discharge counts (rate
      place). After the method is verified over the range of parameters for which
      previous analytical models are applicable, the parameter space is then extended.
      For example, a computational model of AN activity that extends to high
      frequencies is used to explore the common belief that rate-place information is
      responsible for frequency encoding at high frequencies due to the rolloff in AN
      phase locking above 2 kHz. This rolloff is thought to eliminate temporal
      information at high frequencies. Contrary to this belief, results of this
      analysis show that rate-place predictions for frequency discrimination are
      inconsistent with human performance in the dependence on frequency for high
      frequencies and that there is significant temporal information in the AN up to at
      least 10 kHz. In fact, the all-information predictions match the functional
      dependence of human performance on frequency, although optimal performance is
      much better than human performance. The use of computational AN models in this
      study provides new constraints on hypotheses of neural encoding of frequency in
      the auditory system; however, the method is limited to simple tasks with
      deterministic stimuli. A companion article in this issue ("Evaluating Auditory
      Performance Limits: II") describes an extension of this approach to more complex
      tasks that include random variation of one parameter, for example, random-level
      variation, which is often used in psychophysics to test neural encoding
      hypotheses.

PMID- 11571000
TI  - Evaluating auditory performance limits: II. One-parameter discrimination with
      random-level variation.
AB  - Previous studies have combined analytical models of stochastic neural responses
      with signal detection theory (SDT) to predict psychophysical performance limits;
      however, these studies have typically been limited to simple models and simple
      psychophysical tasks. A companion article in this issue ("Evaluating Auditory
      Performance Limits: I") describes an extension of the SDT approach to allow the
      use of computational models that provide more accurate descriptions of neural
      responses. This article describes an extension to more complex psychophysical
      tasks. A general method is presented for evaluating psychophysical performance
      limits for discrimination tasks in which one stimulus parameter is randomly
      varied. Psychophysical experiments often randomly vary a single parameter in
      order to restrict the cues that are available to the subject. The method is
      demonstrated for the auditory task of random-level frequency discrimination using
      a computational auditory nerve (AN) model. Performance limits based on AN
      discharge times (all-information) are compared to performance limits based only
      on discharge counts (rate place). Both decision models are successful in
      predicting that random-level variation has no effect on performance in quiet,
      which is the typical result in psychophysical tasks with random-level variation.
      The distribution of information across the AN population provides insight into
      how different types of AN information can be used to avoid the influence of
      random-level variation. The rate-place model relies on comparisons between fibers
      above and below the tone frequency (i.e., the population response), while the all
      information model does not require such across-fiber comparisons. Frequency
      discrimination with random-level variation in the presence of high-frequency
      noise is also simulated. No effect is predicted for all-information, consistent
      with the small effect in human performance; however, a large effect is predicted
      for rate-place in noise with random-level variation.

PMID- 11571001
TI  - Adaptive algorithm for blind separation from noisy time-varying mixtures.
AB  - This article addresses the problem of blind source separation from time-varying
      noisy mixtures using a state variable model and recursive estimation. An estimate
      of each source signal is produced real time at the arrival of new observed
      mixture vector. The goal is to perform the separation and attenuate noise
      simultaneously, as well as to adapt to changes that occur in the mixing system.
      The observed data are projected along the eigenvectors in signal subspace. The
      subspace is tracked real time. Source signals are modeled using low-order AR
      (autoregressive) models, and noise is attenuated by trading off between the model
      and the information provided by measurements. The type of zero-memory
      nonlinearity needed in separation is determined on-line. Predictor-corrector
      filter structures are proposed, and their performance is investigated in
      simulation using biomedical and communications signals at different noise levels
      and a time-varying mixing system. In quantitative comparison to other widely used
      methods, significant improvement in output signal-to-noise ratio is achieved.

PMID- 11571002
TI  - Robust full Bayesian learning for radial basis networks.
AB  - We propose a hierarchical full Bayesian model for radial basis networks. This
      model treats the model dimension (number of neurons), model parameters,
      regularization parameters, and noise parameters as unknown random variables. We
      develop a reversible-jump Markov chain Monte Carlo (MCMC) method to perform the
      Bayesian computation. We find that the results obtained using this method are not
      only better than the ones reported previously, but also appear to be robust with
      respect to the prior specification. In addition, we propose a novel and
      computationally efficient reversible-jump MCMC simulated annealing algorithm to
      optimize neural networks. This algorithm enables us to maximize the joint
      posterior distribution of the network parameters and the number of basis
      function. It performs a global search in the joint space of the parameters and
      number of parameters, thereby surmounting the problem of local minima to a large
      extent. We show that by calibrating the full hierarchical Bayesian prior, we can
      obtain the classical Akaike information criterion, Bayesian information
      criterion, and minimum description length model selection criteria within a
      penalized likelihood framework. Finally, we present a geometric convergence
      theorem for the algorithm with homogeneous transition kernel and a convergence
      theorem for the reversible-jump MCMC simulated annealing method.

PMID- 11571003
TI  - Longitudinal predictors of depressive symptoms among low income injection drug
      users.
AB  - Effects of changes in physical health status and drug use, and prior social
      support on depressive symptoms were assessed in low income injection drug users.
      Data are from participants (n = 503) enrolled at baseline (1994-1995) who
      remained at one-year follow-up (79%), of whom 37% were HIV-positive and 36%
      female. Physical health was measured by HIV symptoms, AIDS, CD4 count and
      functional limitation (IADLs). One-third scored high on depressive symptoms (CES
      D > or = 16) at one-year follow-up, representing no statistically significant
      change from baseline (38%). In multiple logistic regression, after controlling
      for baseline depression scores (OR = 6.11, p < 0.001) and drug use (OR = 1.20, p
      = 0.192), baseline functional limitation (OR = 3.28, p < 0.001) and declining
      functioning (OR = 3.60, p < 0.001) were positively, and quitting drug use was
      negatively, associated with depressive symptoms at follow-up. Low social support
      at baseline (OR = 0.58, p < 0.10) was marginally predictive of depressive
      symptoms. Depressive symptoms did not differ by gender. For HIV-positive
      respondents, functional limitation was predictive of depressive symptoms, but HIV
      illness and drug use were not. Facilitating drug treatment and preventive medical
      care may aid in reducing depression in this population. For HIV-positive drug
      users, drug treatment prior to AIDS may help reduce depressive symptoms, with
      potential implications for HIV service utilization and medical adherence.

PMID- 11571004
TI  - Drug users talk about HIV testing: motivating and deterring factors.
AB  - Injection drug use plays a critical role in the spread of HIV/AIDS, with an
      estimated 19,000 drug users infected each year. Counselling and testing services
      can be an important gateway for engaging HIV-infected individuals into medical
      care and can positively influence the preventive behaviours of IDUs. This study
      seeks to document and understand the complexity and range of motivations and
      deterrents to HIV testing among IDUs. Participants were recruited using a
      convenience sampling method. Interviews consisted of a qualitative guide and a
      quantitative survey to collect HIV testing histories, sex and drug risk
      behaviours, and demographic information. Interview data was coded and content
      analyzed to identify emerging themes and clarify the processes that drug users
      employ in deciding whether or not to test. Sixty-six drug users were interviewed.
      The sample reported a median of four lifetime HIV tests. Participants described a
      range of motivating and deterring factors to HIV testing across personal,
      interpersonal and structural categories. Drug users' decision to test is
      influenced by a complex network of factors. Better understanding of these
      motivators and deterrents can help providers develop a more holistic approach to
      targeting this high-risk population for HIV prevention efforts.

PMID- 11571005
TI  - Crack smokers' intention to use condoms with loved partners: intervention
      development using the theory of reasoned action, condom beliefs, and processes of
      change.
AB  - Prevalence rates of HIV infection acquired through heterosexual contacts have
      risen steadily since 1982. Crack cocaine smokers are at particular risk of HIV
      infection due to heterosexual exposure. HIV risk reduction interventions seeking
      to increase condom use among drug users have met with minimal success, and there
      is a need for interventions to be strongly grounded in psychosocial models of
      behaviour change. This study presents the results of an investigation of
      predictors of intention to use condoms and related therapy processes among
      heterosexual drug users. Data were analyzed from 586 crack smokers recruited in
      Washington, DC, Miami, Florida, and Collier County, Florida who reported having
      both primary and casual sex partners. Participants responded to items derived
      from the theory of reasoned action, the theory of planned behaviour and the
      transtheoretical model of change. Condom use beliefs and therapy processes used
      to initiate and maintain condom use were assessed. Outcome expectancies and
      normative beliefs were the strongest predictors of intention to use condoms with
      a primary sexual partner. In turn, beliefs that condoms inhibit sexual romance
      and decrease sexual pleasure strongly predicted outcome expectancies. Therapy
      processes found to be associated with these constructs included: self-liberation,
      counter conditioning and stimulus control/reinforcement. Results suggest that HIV
      risk reduction interventions using a group format and targeting condom beliefs
      related to sexual romance and pleasure will decrease negative outcome
      expectancies about condom use. Also, reinforcing attempts to use condoms with
      intimate partners should increase positive outcome expectancies and intention to
      initiate or maintain condoms with a primary sexual partner.

PMID- 11571006
TI  - Women's barriers to HIV-1 testing and disclosure: challenges for HIV-1 voluntary
      counselling and testing.
AB  - In view of the ever-increasing HIV/AIDS epidemic in sub-Saharan Africa, the
      expansion of HIV-1 voluntary counselling and testing (VCT) as an integral part of
      prevention strategies and medical research is both a reality and an urgent need.
      As the availability of HIV-1 VCT grows two limitations need to be addressed,
      namely: low rates of HIV-1 serostatus disclosure to sexual partners and negative
      outcomes of serostatus disclosure. Results from a study among men, women and
      couples at an HIV-1 VCT clinic in Dar es Salaam, Tanzania are presented. The
      individual, relational and environmental factors that influence the decision to
      test for HIV-1 and to share test results with partners are described. The most
      salient barriers to HIV-1 testing and serostatus disclosure described by women
      include fear of partners' reaction, decision-making and communication patterns
      between partners, and partners' attitudes towards HIV-1 testing. Perception of
      personal risk for HIV-1 is the major factor driving women to overcome barriers to
      HIV-1 testing. The implications of findings for the promotion of HIV-1 VCT
      programmes, the implementation of partner notification policies and the
      development of post-test support services are discussed.

PMID- 11571007
TI  - Attitudes to voluntary counselling and testing for HIV among pregnant women in
      rural south-west Uganda.
AB  - This paper describes the results of a study exploring the attitudes of women
      attending maternity clinics to voluntary counselling and testing during pregnancy
      in rural areas in south-west Uganda. It was a qualitative study using focus group
      discussions (FGDs). Twenty-four FGDs were carried out with 208 women attending
      maternity clinics in three sites in rural south-west Uganda. The FGDs were all
      recorded and transcribed, and analysed using standard computer-based qualitative
      techniques. Almost all women were willing in principle to take an HIV test in the
      event of pregnancy, and to reveal their HIV status to maternity staff. They were
      anxious, however, about confidentiality, and there was a widespread fear that
      maternity staff might refuse to assist them when the time came to deliver if
      their status were known. This applied more to traditional birth attendants than
      to biomedical health staff. There were also rumours about medical staff
      intentionally killing HIV-positive patients in order to stem the spread of the
      epidemic. Women were concerned that if their husbands found out they were HIV
      positive they would be blamed and separation or domestic violence might result.
      IN CONCLUSION: although VCT during pregnancy is acceptable in principle, much
      will need to be done to ensure confidentiality and allay women's fears of
      stigmatisation and discrimination during delivery. Community sensitisation will
      be necessary and male partners will have to be involved if interventions are to
      be acceptable.

PMID- 11571008
TI  - Adherence to antiretroviral therapy among HIV-positive children: examination of
      the role of caregiver health beliefs.
AB  - This study examined the association between two components of the Health Belief
      Model (perceived vulnerability and barriers) and adherence to antiretroviral
      therapy (ART) among children who are HIV-infected. The parents/caregivers of 30
      children (mean age = 5.21, SD = 3.18) who were HIV-infected and who were on
      active ART were surveyed to assess current methods of adherence assessment and
      educational efforts within the institution. All participants (except one) were
      African American and reported low monthly family incomes (M = $869.45, SD =
      $832.63). Assessment instruments included measures of perceived vulnerability,
      caregiver-reported adherence and perceived barriers, and objective measures of
      adherence (clinical pill count; electronic measurement). The results failed to
      demonstrate a significant relationship between parental perceived vulnerability,
      perceived barriers and adherence to antiretroviral medications. Methods of
      assessing adherence provided significantly discrepant estimates of adherence.
      Results are discussed in terms of implications for patient care and for future
      research in this area. The addition of behavioural and motivational components to
      traditional educational approaches may positively impact treatment results.

PMID- 11571009
TI  - Anticipated psychological impact of receiving medical feedback about HIV
      treatment outcomes.
AB  - Two hundred and seven persons taking antiretroviral HIV medications rated
      anticipated affective responses to two vignettes depicting different medical
      feedback situations. Participants were randomly assigned to a medical feedback
      vignette which varied between participants by (a) the direction of HIV viral load
      change (increase, decrease, no change) and (b) whether or not a medication change
      was recommended by the physician. The first experimental vignette was always
      followed by a second vignette depicting a viral load decrease (indicating
      treatment success in suppressing the virus). A mixed 3 (viral load change) x 2
      (medication change) x 2 (within-subjects factor) factorial design was used.
      Significant differences in anticipated affective responses to treatment outcome
      situations were found, suggesting feedback about success or failure of treatment
      regimens impacts psychosocial adjustment of persons living with HIV.

PMID- 11571010
TI  - Cost-effectiveness of prevention referrals for high-risk HIV-negatives in San
      Francisco.
AB  - We retrospectively assessed the cost-effectiveness of providing prevention
      referrals to high-risk seronegatives at HIV test sites in San Francisco. We
      examined the costs and effects from the perspectives of society and the San
      Francisco Department of Public Health (SFDPH). Cost categories assessed included
      referral materials, counsellor training and time required to make referrals,
      prevention services and the value of client time. Effect data are drawn from a
      study of 289 high-risk seronegatives and the published literature, and are
      applied to a city-wide caseload of 6,626 high-risk seronegatives. We estimate
      that a city-wide programme in San Francisco averts two HIV infections per year
      and yields net savings to society of $43,765, with a cost to the SFDPH of $20,738
      per HIV infection averted. We conclude that providing HIV prevention referrals to
      high-risk seronegatives receiving antibody testing imposes significant costs, but
      has attractive cost-effectiveness when applied to a large high-risk population.

PMID- 11571011
TI  - The acceptability of HIV immunization: examining vaccine characteristics as
      determining factors.
AB  - The acceptance of a future HIV vaccine may be influenced, in part, by the
      characteristics of the vaccine itself. This study evaluated the relationship of
      vaccine characteristics to acceptability of hypothetical HIV immunization.
      Subjects were 549 undergraduates (18-56 years of age); 70.3% were female, and
      80.4% were non-Hispanic white. Subjects completed a self-administered
      questionnaire assessing a series of 12 hypothetical vaccines that varied along
      the dimensions of efficacy (80 or 50%), cost (free or $300) and social saturation
      or percentage of the population already vaccinated (10, 50 or 90%). The vaccines
      were each rated on an 11-point scale ranging from zero ('I will never get this
      vaccine') to 100 ('I will definitely get this vaccine'), in increments of ten.
      All three dimensions were significantly associated with probability of vaccine
      acceptance, particularly vaccine efficacy and cost. The highest rated vaccine
      (free, 80% efficacious, 90% saturation level) received a mean acceptability score
      of 83.4, whereas the lowest rated vaccine ($300, 50% efficacious, 10% saturation
      level) received a mean score of 32.8. The mean acceptability rating across all 12
      vaccines was 55.14. These findings indicate the potential importance of
      considering the influence of vaccine characteristics in future HIV immunization
      programmes.

PMID- 11571012
TI  - Effects of mental health centre staff turnover on HIV/AIDS service delivery
      integration.
AB  - This study examined the effects of mental health service provider turnover rates
      on system integration. System integration was defined as appropriate referrals
      and the freeflow exchange of information among three components: mental health
      care, primary health care, and dedicated HIV care coordination services. From a
      sample of 17 mental health centres across a midwestern state, higher staff
      turnover rates did not negatively impact integration, with the exception of
      within-centre services. Mental health service providers are aware of who other
      network providers are, but integration breaks down at a level of implementation
      in terms of contacts, exchange of information and referrals. Integrative efforts
      focused on care coordination with little to no evidence of bidirectionality.

PMID- 11571013
TI  - Reducing social vulnerability to HIV/AIDS: models of care and their impact in
      resource-poor settings.
AB  - There has been an increasing understanding of the social, economic, cultural and
      political factors that have shaped the HIV/AIDS epidemic. It has been widely
      recognized that in order to have effective prevention programmes for HIV/AIDS,
      the broader determinants of health must be addressed. Concurrently, a deeper
      understanding of personal and societal vulnerability to HIV/AIDS has emerged.
      Some prevention efforts have expanded their focus, addressing not only individual
      risk factors and behaviour, but also social justice and including community
      mobilization activities to address the wider context of the disease. However, the
      transition to an expanded approach to mitigating the effects of the HIV/AIDS
      epidemic has not been complete. There is little evidence that care and support
      strategies have systematically tried to address these concepts. While the role
      care plays in prevention is considered vital, viewing models of care in terms of
      their impact on the social vulnerability of certain groups to HIV/AIDS has been
      largely neglected. Yet appropriate care programmes that help reduce vulnerability
      will arguably also make the greatest contribution for prevention. Drawing on
      examples of the role social vulnerability has played in prevention efforts, this
      paper evaluates the impact of HIV/AIDS care models on socially vulnerable groups,
      such as women and children.

PMID- 11571014
TI  - Sociodemographic characteristics and HIV risk behaviour patterns of male sex
      workers in Madrid, Spain.
AB  - This paper describes the sociodemographic and work characteristics, prevalence of
      HIV infection and associated risk behaviours among male sex workers (MSWs) in
      Madrid (Spain). Using an anonymous semi-structured questionnaire, educators
      attached to a mobile unit under a street-based prostitution programme surveyed 84
      MSWs from several Madrid areas. Of the total surveyed: 35% were immigrants, mean
      age was 23 years, mean period in prostitution was four years; 21% had no primary
      education; 16% had injected drugs at some time; 11% reported private sexual
      relationships exclusively with women; 89% always used condoms in anal practices
      with clients; and 41% were in sexual relationships with their partners. Only 11%
      had ever used fortified condoms. In the preceding month, 37% had experienced
      condom failure, 82% without having used any lubricant. In all, 67% reported
      having undergone HIV testing, with a higher percentage of positive results among
      injecting (60%) versus non-injecting drug users (17%). Immigrants had a lower
      level of education, made less use of condoms, had more condom failures and, in
      their private lives, a greater proportion reported sexual relationships
      exclusively with women. In Spain, MSWs should be included in HIV prevention
      programmes, which ought to be specifically adapted to immigrants. Priority should
      be given to reducing the condom failure rate in anal intercourse, by improving
      access to fortified condoms.

PMID- 11571016
TI  - World Health Organization Global AIDS statistics.

PMID- 11571017
TI  - Time-dose relationships in radiation-enhanced integration.
AB  - PURPOSE: We have shown that ionizing radiation increases recombination, as
      manifested by increased stable transduction of both plasmid and adenoviral
      vectors. This paper reports the duration of increased recombination after
      irradiation. MATERIALS AND METHODS: A549 or NIH/3T3 cells were transfected at
      various times after irradiation. Cells were also irradiated with several
      fractionation schemes and then transfected. RESULTS: Enhanced integration (EI) is
      a very long-lived process, lasting at least 2-3 days after single radiation
      fractions. The duration of EI activation is radiation dose-dependent. The
      efficiency of EI is dependent on radiation dose and independent of fractionation,
      such that low dose-rate, fractionated and single radiation doses result in
      similar levels of EI when corrected for differences in cytotoxicity. CONCLUSIONS:
      Radiation, given with fraction sizes and dose-rates used in clinical radiation
      therapy, induces a long-lived hyper-recombination state. Since radiotherapy is
      already a component of treatment for many malignancies and is integrated into
      radiation-gene therapy trials, an understanding of recombination events that
      improve gene delivery is important and timely.

PMID- 11571018
TI  - Impact of radiation quality on the spectrum of induced chromosome exchange
      aberrations.
AB  - PURPOSE: To study the impact of radiation quality on the spectrum of chromosome
      exchange aberrations in human lymphocytes using chromosome arm-specific and
      telomeric probes. The analysis is focused on: (1) incomplete exchanges, (2)
      interstitial fragments, (3) interarm intrachanges and (4) the complexity of the
      aberration patterns. The present data after neutron exposure are compared with
      previously obtained data after X-irradiation. MATERIALS AND METHODS: Isolated
      human lymphocytes from three donors were irradiated with 1 MeV fast neutrons
      (0.25, 0.5, 1.0, 1.5, 2.0 Gy). Analysis was performed on first post-irradiation
      metaphases with arm-specific probes for chromosome 1 in combination with a pan
      centromeric probe, or with telomeric and centromeric PNA probes. RESULTS: In
      comparison with X-rays, exposure to neutrons leads to: (1) similar frequencies of
      incomplete exchanges or terminal deletions, (2) a significantly higher induction
      of both inter- and intraarm intrachanges, (3) a higher proportion of complex
      aberrations, and (4) aberrations with a higher degree of complexity, i.e. derived
      from more chromosome breaks which interact more frequently in a non-reciprocal
      fashion. Essentially no dose dependence was found for the yield ratios between
      the various types of chromosomal aberrations. CONCLUSIONS: Despite the reduced
      rejoining deficiency of DNA double-strand breaks induced by high-LET radiation,
      exposure to neutrons does not lead to enhanced levels of unrejoined chromosome
      breaks that can be observed as incomplete exchanges in cells that have reached
      mitosis. Proximity effects are more pronounced after densely ionizing radiation
      than after sparsely ionizing radiation. Clustered damage produced by neutron
      tracks results in a high proportion of complex aberrations and in non-reciprocal
      interactions of chromosome breaks. Most of the exchanges occur within one neutron
      track and little interaction seems to take place between the breaks formed in
      different tracks.

PMID- 11571019
TI  - The XRCC2 human repair gene influences recombinational rearrangements leading to
      chromatid breaks.
AB  - PURPOSE: To test the possible involvement of the XRCC2 gene in the control of
      intra- versus interchromatid rearrangements leading to chromatid breaks in G2
      cells by studying the colour-switch ratio (CSR) in harlequin-stained Chinese
      hamster irs1 cells. MATERIALS AND METHODS: The V79-4 mutant cell lines irs1
      (XRCC2 mutation) and irs2 (XRCC8 mutation), two WT V79 lines and GT621-1 (irs1
      transfected with the XRCC2 gene) were labelled with BrdU through two cell cycles,
      irradiated and sampled 1.5h after exposure. Metaphase spreads were analysed for
      chromatid break frequency and frequencies of colour-switch (colour-switch between
      chromatids at the break point) and non-colour-switch breaks, from which the CSR
      was calculated. RESULTS: Chromatid breaks were induced linearly with dose in all
      lines, and frequencies were elevated in irs1 and irs2 mutant cell lines when
      compared with WT lines. An XRCC2 transfected line (GT621-1) showed full
      radiosensitivity complementation with respect to frequencies of chromatid breaks.
      The CSR was significantly higher in irs1 (13.9%) than in the parental V79-4
      (7.5%) or irs2 (4.9%) cells. GT621-1 cells showed partial, but significant
      complementation with respect to CSR (9.2%). CONCLUSIONS: It is concluded that the
      significantly higher CSR for the irs1 mutant than for the wild-type parental V79
      4 line indicates the involvement of the XRCC2 gene product in the control of the
      rearrangement process leading to chromatid breaks.

PMID- 11571020
TI  - Involvement of c-Jun NH2-terminal kinase-1 in heat-induced apoptotic cell death
      of human monoblastic leukaemia U937 cells.
AB  - PURPOSE: To determine the involvement of c-Jun NH(2)-terminal kinase-1 (JNK1) and
      possibly of HSP27 in heat-induced apoptosis of human monoblastic leukaemia U937
      cells. MATERIALS AND METHODS: Dominant negative JNK1 (APF), in which the
      phosphorylation sites Thr-Pro-Tyr were changed to Ala-Pro-Phe, was overexpressed
      in U937 cells. Cell viability and DNA fragmentation were analysed by the
      erythrosin-B dye exclusion test and by agarose gel electrophoresis, respectively.
      Expression of activated caspase-9, phosphorylated JNK1, JNK2, p38 and HSP27 was
      examined by Western blotting. JNK1 kinase assay was also performed using c-Jun as
      a substrate. RESULTS: Loss of viability, activated cleavage form of caspase-9 and
      DNA fragmentation were rapid in U937 cells after 44 degrees C hyperthermia, while
      overexpression of dominant negative JNK1 interfered with phosphorylation or
      activation of JNK1 without affecting that of JNK2 or p38/SAPK, and apparently
      delayed or reduced cleavage and activation of caspase-9, DNA fragmentation and
      cell death. Heat-induced phosphorylation of HSP27, observed in parental U937
      cells, was suppressed and only slightly detectable in jnk1 mutant cells.
      CONCLUSIONS: Prolonged phosphorylation or activation of JNK1 was considered
      important for heat-induced apoptosis and JNK1 may control the process possibly
      through phosphorylation of HSP27 and caspase-9 activation in U937 cells.

PMID- 11571021
TI  - Increased body weight in C57BL/6 female mice after exposure to ionizing radiation
      or 60Hz magnetic fields.
AB  - PURPOSE: The purpose of this investigation was to determine whether early
      treatment with ionizing radiation and/or chronic magnetic field (MF) exposure
      affected body weight in female mice. MATERIALS AND METHODS: Weanling C57BL/6
      female mice were irradiated with four equal weekly cobalt-60 exposures (total
      cumulative doses: 3.0, 4.0, 5.1Gy) and/or received chronic lifetime exposure to
      1.4 mT 60 Hz circularly polarized MF or ambient MF. The body weights of 2280 mice
      were recorded at 35 age intervals, and analysis of variance was used to compare
      the mean differences from baseline weights between treatment groups and sham
      exposed controls. RESULTS: A highly statistically significant effect of ionizing
      radiation on body weight was observed at 28 age intervals (p < or = 0.001), and
      for MF exposure at 10 age intervals (p < or = 0.001). During the young adult
      growth phase, mice exposed only to MF exhibited < or =0.5 g greater weight gain
      relative to sham-exposed controls (p = 0.0001). The effect of ionizing radiation
      alone was inversely related to dose, with the largest weight increases observed
      in all of the irradiated groups after 9-12 months (p = 0.0001). CONCLUSIONS:
      Treatment with split-dose ionizing radiation at an early age and chronic exposure
      to a residential power frequency MF were found to produce small but significant
      increases in body weight.

PMID- 11571022
TI  - Effect of increased intracellular melanin concentration on survival of human
      melanoma cells exposed to different wavelengths of UV radiation.
AB  - PURPOSE: To investigate the effect of intracellular melanin content on cell
      survival of G361 human melanoma cells following exposure to UV radiation.
      MATERIALS AND METHODS: Cells were cultured in medium containing elevated
      concentrations of L tyrosine phosphate and L glutamine to increase their melanin
      content. Cell survival was assessed by colony-forming ability in treated and
      untreated cells following exposure to 254 nm germicidal UVC radiation (0-60 J m(
      2)), 311 nm UVB radiation (0-5 kJ m(-2)), or broadband UVA radiation (Sellamed
      4000, maximum output between 350 and 450 nm) (0-1.2 MJ m(-2)). RESULTS: Treated
      cells, with a 2-fold increase in total melanin concentration and an increased
      ratio of eumelanin to pheomelanin, were marginally more resistant than untreated
      control cells to cell killing by 311 nm UVB radiation, but treatment had no
      effect on killing by germicidal UVC or broadband UVA radiation. CONCLUSIONS:
      There was no evidence of any photosensitizing effect of increased melanin on
      human melanoma cell survival following exposure to UVC, UVB or broadband UVA
      radiation. The slight protective effect seen following exposure to UVB radiation
      may have been due to increased scavenging of reactive-oxygen species,
      particularly by eumelanin, at this wavelength.

PMID- 11571023
TI  - Instability of microsatellites in radiation-associated thyroid tumours with short
      latency periods.
AB  - PURPOSE: To determine the instability of microsatellite sequences in post
      Chernobyl thyroid tumours from children and young adults, and to ascertain
      whether they correlated with the age of the patient at the time of the accident
      and the tumour latency period. MATERIALS AND METHODS: The stability of 26
      microsatellite markers was investigated in 122 radiation-associated thyroid
      tumours (96 children, 26 adults) from Belarus and 39 spontaneous thyroid tumours
      (adults) from Munich without radiation history. RESULTS: A significant
      correlation between patient age at the time of the accident and the instability
      of microsatellite sequences was established. Also, a high instability of
      microsatellite sequences was found in 28 early thyroid tumours from Belarus with
      latency periods of 6-8 years, in contrast to a low instability of microsatellites
      in 94 tumours emerging 9-11 years after the accident. Microsatellite instability
      in the reference group from Munich proved similar to the early thyroid tumours
      from Belarus. CONCLUSION: Early, fast-growing and aggressive post-Chernobyl
      thyroid tumours are characterized by an increase in microsatellite instability.

PMID- 11571026
TI  - The concept of episodic memory.

PMID- 11571024
TI  - FISH examination of lymphocytes from Mayak workers for assessment of
      translocation induction rate under chronic radiation exposures.
AB  - PURPOSE: To estimate the translocation-induction rate under chronic exposure
      conditions by measuring chromosome aberration frequencies in lymphocytes from
      Mayak nuclear workers using fluorescence in situ hybridization (FISH). MATERIALS
      AND METHODS: Lymphocytes were examined from 27 nuclear workers at the Mayak
      Production Association and two control individuals using FISH with probes for
      chromosomes 1, 2 and 4. Official doses derived from worker film-badge records
      varied from 0 to 8.50 Gy. RESULTS: The mean (+/-SD) genome-equivalent
      translocation frequency (F(G)) was 2.30 (+/-0.75)% in the zero-dose group (n =
      7), and Poisson regression analysis provided the best-fit equation of F(G)(%) =
      2.96(+/-0.39) + 0.69(+/-0.14)D + 0.12(+/-0.05)A, where D is the film-badge
      derived dose (Gy), and A is age centred at 67 years. The induction rate would
      increase to nearly 1% Gy(-1) if the radiation dose to bone marrow, one of the
      major organs for lymphocytes and where their precursor cells reside, is
      considered. CONCLUSION: The estimated induction rate in vivo appeared
      substantially smaller than linear coefficients estimated from various in vitro
      studies.

PMID- 11571027
TI  - Episodic memory and autonoetic consciousness: a first-person approach.
AB  - Episodic memory is identified with autonoetic consciousness, which gives rise to
      remembering in the sense of self-recollection in the mental re-enactment of
      previous events at which one was present. Autonoetic consciousness is
      distinguished from noetic consciousness, which gives rise to awareness of the
      past that is limited to feelings of familiarity or knowing. Noetic consciousness
      is identified not with episodic but with semantic memory, which involves general
      knowledge. A recently developed approach to episodic memory makes use of 'first
      person' reports of remembering and knowing. Studies using this approach have
      revealed many independent variables that selectively affect remembering and
      others that selectively affect knowing. These studies can also be interpreted in
      terms of distinctiveness and fluency of processing. Remembering and knowing do
      not correspond with degrees of confidence in memory. Nor does remembering always
      control the memory response. There is evidence that remembering is selectively
      impaired in various populations, including not only amnesic patients and older
      adults but also adults with Asperger's syndrome. This first-person approach to
      episodic memory represents one way in which that most elusive aspect of
      consciousness, its subjectivity, can be investigated scientifically. The two
      kinds of conscious experiences can be manipulated experimentally in ways that are
      systematic, replicable and intelligible theoretically.

PMID- 11571028
TI  - Components of episodic memory: the contribution of recollection and familiarity.
AB  - The examination of recognition memory confidence judgements indicates that there
      are two separate components or processes underlying episodic memory. A model that
      accounts for these results is described in which a recollection process and a
      familiarity process are assumed to contribute to recognition memory performance.
      Recollection is assumed to reflect a threshold process whereby qualitative
      information about the study event is retrieved, whereas familiarity reflects a
      classical signal-detection process whereby items exceeding a familiarity response
      criterion are accepted as having been studied. Evidence from cognitive,
      neuropsychological and neuroimaging studies indicate that the model is in
      agreement with the existing recognition results, and indicate that recollection
      and familiarity are behaviourally, neurally and phenomenologically distinct
      memory retrieval processes.

PMID- 11571029
TI  - Sensory-perceptual episodic memory and its context: autobiographical memory.
AB  - Episodic memory is reconceived as a memory system that retains highly detailed
      sensory perceptual knowledge of recent experience over retention intervals
      measured in minutes and hours. Episodic knowledge has yet to be integrated with
      the autobiographical memory knowledge base and so takes as its context or
      referent the immediate past of the experiencing self (or the 'I'). When recalled
      it can be accessed independently of content and is recollectively experienced.
      Autobiographical memory, in contrast, retains knowledge over retention intervals
      measured in weeks, months, years, decades and across the life span.
      Autobiographical knowledge represents the experienced self (or the 'me'), is
      always accessed by its content and, when accessed, does not necessarily give rise
      to recollective experience. Instead, recollective experience occurs when
      autobiographical knowledge retains access to associated episodic memories. In
      this reworking of the 'episodic memory' concept autobiographical memory provides
      the instantiating context for sensory-perceptual episodic memory.

PMID- 11571030
TI  - Misattribution, false recognition and the sins of memory.
AB  - Memory is sometimes a troublemaker. Schacter has classified memory's
      transgressions into seven fundamental 'sins': transience, absent-mindedness,
      blocking, misattribution, suggestibility, bias and persistence. This paper
      focuses on one memory sin, misattribution, that is implicated in false or
      illusory recognition of episodes that never occurred. We present data from
      cognitive, neuropsychological and neuroimaging studies that illuminate aspects of
      misattribution and false recognition. We first discuss cognitive research
      examining possible mechanisms of misattribution associated with false
      recognition. We also consider ways in which false recognition can be reduced or
      avoided, focusing in particular on the role of distinctive information. We next
      turn to neuropsychological research concerning patients with amnesia and
      Alzheimer's disease that reveals conditions under which such patients are less
      susceptible to false recognition than are healthy controls, thus providing clues
      about the brain mechanisms that drive false recognition. We then consider
      neuroimaging studies concerned with the neural correlates of true and false
      recognition, examining when the two forms of recognition can and cannot be
      distinguished on the basis of brain activity. Finally, we argue that even though
      misattribution and other memory sins are annoying and even dangerous, they can
      also be viewed as by-products of adaptive features of memory.

PMID- 11571031
TI  - Theories of episodic memory.
AB  - Theories of episodic memory need to specify the encoding (representing), storage,
      and retrieval processes that underlie this form of memory and indicate the brain
      regions that mediate these processes and how they do so. Representation and re
      representation (retrieval) of the spatiotemporally linked series of scenes, which
      constitute an episode, are probably mediated primarily by those parts of the
      posterior neocortex that process perceptual and semantic information. However,
      some role of the frontal neocortex and medial temporal lobes in representing
      aspects of context and high-level visual object information at encoding and
      retrieval cannot currently be excluded. Nevertheless, it is widely believed that
      the frontal neocortex is mainly involved in coordinating episodic encoding and
      retrieval and that the medial temporal lobes store aspects of episodic
      information. Establishing where storage is located is very difficult and
      disagreement remains about the role of the posterior neocortex in episodic memory
      storage. One view is that this region stores all aspects of episodic memory ab
      initio for as long as memory lasts. This is compatible with evidence that the
      amygdala, basal forebrain, and midbrain modulate neocortical storage. Another
      view is that the posterior neocortex only gradually develops the ability to store
      some aspects of episodic information as a function of rehearsal over time and
      that this information is initially stored by the medial temporal lobes. A third
      view is that the posterior neocortex never stores these aspects of episodic
      information because the medial temporal lobes store them for as long as memory
      lasts in an increasingly redundant fashion. The last two views both postulate
      that the medial temporal lobes initially store contextual markers that serve to
      cohere featural information stored in the neocortex. Lesion and functional
      neuroimaging evidence still does not clearly distinguish between these views.
      Whether the feeling that an episodic memory is familiar depends on retrieving an
      association between a retrieved episode and this feeling, or by an attribution
      triggered by a priming process, is unclear. Evidence about whether the
      hippocampus and medial temporal lobe cortices play different roles in episodic
      memory is conflicting. Identifying similarities and differences between episodic
      memory and both semantic memory and priming will require careful componential
      analysis of episodic memory.

PMID- 11571032
TI  - The loss of episodic memories in retrograde amnesia: single-case and group
      studies.
AB  - Retrograde amnesia in neurological disorders is a perplexing and fascinating
      research topic. The severity of retrograde amnesia is not well correlated with
      that of anterograde amnesia, and there can be disproportionate impairments of
      either. Within retrograde amnesia, there are various dissociations which have
      been claimed-for example, between the more autobiographical (episodic) and more
      semantic components of memory. However, the associations of different types of
      retrograde amnesia are also important, and clarification of these issues is
      confounded by the fact that retrograde amnesia seems to be particularly
      vulnerable to psychogenic factors. Large frontal and temporal lobe lesions have
      been postulated as critical in producing retrograde amnesia. Theories of
      retrograde amnesia have encompassed storage versus access disruption,
      physiological processes of 'consolidation', the progressive transformation of
      episodic memories into a more 'semantic' form, and multiple-trace theory. Single
      case investigations, group studies and various forms of neuroimaging can all
      contribute to the resolution of these controversies.

PMID- 11571033
TI  - Episodic memory: insights from semantic dementia.
AB  - Semantic dementia, also known as the temporal lobe variant of fronto-temporal
      dementia, results in a progressive yet relatively pure loss of semantic knowledge
      about words, objects and people, and is associated with asymmetric, focal atrophy
      of the antero-lateral temporal lobes. Semantic dementia provides a unique
      opportunity to study the organization of long-term memory particularly since
      initial observations suggested sparing of episodic memory. Recent studies reveal,
      however, a more complex but theoretically revealing pattern. On tests of
      autobiographical memory, patients with semantic dementia show a 'reverse step
      function' with sparing of recall of events from the most recent 2 to 5 years but
      impairment on more distant life periods. Anterograde recognition memory for
      visual materials is extremely well preserved, except in the most deteriorated
      cases, although performance is heavily reliant upon perceptual information about
      the studied stimuli, particularly for items that are no longer known by the
      subjects. On tests of verbal anterograde memory such as word learning,
      performance is typically poor even for words which are 'known' to the patients. A
      source discrimination experiment, designed to evaluate familiarity and
      recollection-based anterograde memory processes, found that patients with
      semantic dementia showed good item detection, although recollection of source was
      sometimes impaired. Semantic knowledge about studied items and measures of item
      detection and source discrimination were largely independent. The implications of
      these findings for models of long-term memory are discussed. The results support
      the concept that episodic memory, or at least the recall of temporally specific
      autobiographical experiences, draws upon a number of separable memory processes,
      some of which can function independently of semantic knowledge.

PMID- 11571034
TI  - Dissociations in cognitive memory: the syndrome of developmental amnesia.
AB  - The dearth of studies on amnesia in children has led to the assumption that when
      damage to the medial temporal lobe system occurs early in life, the compensatory
      capacity of the immature brain rescues memory functions. An alternative view is
      that such damage so interferes with the development of learning and memory that
      it results not in selective cognitive impairments but in general mental
      retardation. Data will be presented to counter both of these arguments. Results
      obtained from a series of 11 amnesic patients with a history of hypoxic ischaemic
      damage sustained perinatally or during childhood indicate that regardless of age
      at onset of hippocampal pathology, there is a pronounced dissociation between
      episodic memory, which is severely impaired, and semantic memory, which is
      relatively preserved. A second dissociation is characterized by markedly impaired
      recall and relatively spared recognition leading to a distinction between
      recollection-based versus familiarity-based judgements. These findings are
      discussed in terms of the locus and extent of neuropathology associated with
      hypoxic ischaemic damage, the neural basis of 'remembering' versus 'knowing', and
      a hierarchical model of cognitive memory.

PMID- 11571035
TI  - Neuroimaging studies of autobiographical event memory.
AB  - Commonalities and differences in findings across neuroimaging studies of
      autobiographical event memory are reviewed. In general terms, the overall pattern
      across studies is of medial and left-lateralized activations associated with
      retrieval of autobiographical event memories. It seems that the medial frontal
      cortex and left hippocampus in particular are responsive to such memories.
      However, there are also inconsistencies across studies, for example in the
      activation of the hippocampus and dorsolateral prefrontal cortex. It is likely
      that methodological differences between studies contribute to the disparate
      findings. Quantifying and assessing autobiographical event memories presents a
      challenge in many domains, including neuroimaging. Methodological factors that
      may be pertinent to the interpretation of the neuroimaging data and the design of
      future experiments are discussed. Consideration is also given to aspects of
      memory that functional neuroimaging might be uniquely disposed to examine. These
      include assessing the functionality of damaged tissue in patients and the
      estimation of inter-regional communication (effective connectivity) between
      relevant brain regions.

PMID- 11571036
TI  - Episodic-like memory in animals: psychological criteria, neural mechanisms and
      the value of episodic-like tasks to investigate animal models of
      neurodegenerative disease.
AB  - The question of whether any non-human species displays episodic memory is
      controversial. Associative accounts of animal learning recognize that behaviour
      can change in response to single events but this does not imply that animals need
      or are later able to recall representations of unique events at a different time
      and place. The lack of language is also relevant, being the usual medium for
      communicating about the world, but whether it is critical for the capacity to
      represent and recall events is a separate matter. One reason for suspecting that
      certain animals possess an episodic-like memory system is that a variety of
      learning and memory tasks have been developed that, even though they do not meet
      the strict criteria required for episodic memory, have an 'episodic-like'
      character. These include certain one-trial learning tasks, scene-specific
      discrimination learning, multiple reversal learning, delayed matching and non
      matching tasks and, most recently, tasks demanding recollection of 'what, where
      and when' an event happened. Another reason is that the neuronal architecture of
      brain areas thought to be involved in episodic memory (including the hippocampal
      formation) are substantially similar in mammals and, arguably, all vertebrates.
      Third, our developing understanding of activity-dependent synaptic plasticity
      (which is a candidate neuronal mechanism for encoding memory traces) suggests
      that its expression reflects certain physiological characteristics that are ideal
      components of a neuronal episodic memory system. These include the apparently
      digital character of synaptic change at individual terminals and the variable
      persistence of potentiation accounted for by the synaptic tag hypothesis. A
      further value of studying episodic-like memory in animals is the opportunity it
      affords to model certain kinds of neurodegenerative disease that, in humans,
      affect episodic memory. An example is recent work on a transgenic mouse that over
      expresses a mutation of human amyloid precursor protein (APP) that occurs in
      familial Alzheimer's disease, under the control of platelet derived (PD) growth
      factor promoter (the PDAPP mouse). A striking age- and amyloid plaque-related
      deficit is seen using a task in which the mice have to keep changing their memory
      representation of the world rather than learn a single fact.

PMID- 11571037
TI  - Neural systems underlying episodic memory: insights from animal research.
AB  - Two strategies used to uncover neural systems for episodic-like memory in animals
      are discussed: (i) an attribute of episodic memory (what? when? where?) is
      examined in order to reveal the neuronal interactions supporting that component
      of memory; and (ii) the connections of a structure thought to be central to
      episodic memory in humans are studied at a level of detail not feasible in
      humans. By focusing on spatial memory (where?) and the hippocampus, it has proved
      possible to bring the strategies together. A review of lesion, disconnection and
      immediate early-gene studies in animals reveals the importance of interactions
      between the hippocampus and specific nuclei in the diencephalon (most notably the
      anterior thalamic nuclei) for spatial memory. Other parts of this extended
      hippocampal system include the mammillary bodies and the posterior cingulate
      (retrosplenial) cortex. Furthermore, by combining lesion and immediate early-gene
      studies it is possible to show how the loss of one component structure or tract
      can influence the remaining regions in this group of structures. The validity of
      this convergent approach is supported by new findings showing that the same set
      of regions is implicated in anterograde amnesia in humans.

PMID- 11571038
TI  - Elements of episodic-like memory in animals.
AB  - A number of psychologists have suggested that episodic memory is a uniquely human
      phenomenon and, until recently, there was little evidence that animals could
      recall a unique past experience and respond appropriately. Experiments on food
      caching memory in scrub jays question this assumption. On the basis of a single
      caching episode, scrub jays can remember when and where they cached a variety of
      foods that differ in the rate at which they degrade, in a way that is
      inexplicable by relative familiarity. They can update their memory of the
      contents of a cache depending on whether or not they have emptied the cache site,
      and can also remember where another bird has hidden caches, suggesting that they
      encode rich representations of the caching event. They make temporal
      generalizations about when perishable items should degrade and also remember the
      relative time since caching when the same food is cached in distinct sites at
      different times. These results show that jays form integrated memories for the
      location, content and time of caching. This memory capability fulfils Tulving's
      behavioural criteria for episodic memory and is thus termed 'episodic-like'. We
      suggest that several features of episodic memory may not be unique to humans.

PMID- 11571039
TI  - Memory for events and their spatial context: models and experiments.
AB  - The computational role of the hippocampus in memory has been characterized as:
      (i) an index to disparate neocortical storage sites; (ii) a time-limited store
      supporting neocortical long-term memory; and (iii) a content-addressable
      associative memory. These ideas are reviewed and related to several general
      aspects of episodic memory, including the differences between episodic,
      recognition and semantic memory, and whether hippocampal lesions differentially
      affect recent or remote memories. Some outstanding questions remain, such as:
      what characterizes episodic retrieval as opposed to other forms of read-out from
      memory; what triggers the storage of an event memory; and what are the neural
      mechanisms involved? To address these questions a neural-level model of the
      medial temporal and parietal roles in retrieval of the spatial context of an
      event is presented. This model combines the idea that retrieval of the rich
      context of real-life events is a central characteristic of episodic memory, and
      the idea that medial temporal allocentric representations are used in long-term
      storage while parietal egocentric representations are used to imagine, manipulate
      and re-experience the products of retrieval. The model is consistent with the
      known neural representation of spatial information in the brain, and provides an
      explanation for the involvement of Papez's circuit in both the representation of
      heading direction and in the recollection of episodic information. Two
      experiments relating to the model are briefly described. A functional
      neuroimaging study of memory for the spatial context of life-like events in
      virtual reality provides support for the model's functional localization. A
      neuropsychological experiment suggests that the hippocampus does store an
      allocentric representation of spatial locations.

PMID- 11571040
TI  - Episodic memory and common sense: how far apart?
AB  - Research has revealed facts about human memory in general and episodic memory in
      particular that deviate from both common sense and previously accepted ideas.
      This paper discusses some of these deviations in light of the proceedings of The
      Royal Society's Discussion Meeting on episodic memory. Retrieval processes play a
      more critical role in memory than commonly assumed; people can remember events
      that never happened; and conscious thoughts about one's personal past can take
      two distinct forms-'autonoetic' remembering and 'noetic' knowing. The serial
      dependent-independent (SPI) model of the relations among episodic, semantic and
      perceptual memory systems accounts for a number of puzzling phenomena, such as
      some amnesic patients' preserved recognition memory and their ability to learn
      new semantic facts, and holds that episodic remembering of perceptual information
      can occur only by virtue of its mediation through semantic memory. Although
      common sense endows many animals with the ability to remember their past
      experiences, as yet there is no evidence that humanlike episodic memory-defined
      in terms of subjective time, self, and autonoetic awareness-is present in any
      other species.

PMID- 11571042
TI  - Phylogenetic evidence for colour pattern convergence in toxic pitohuis: Mullerian
      mimicry in birds?
AB  - Bird species in the genus Pitohui are chemically defended by a potent neurotoxic
      alkaloid in their skin and feathers. The two most toxic pitohui species, the
      hooded pitohui (Pitohui dichrous) and the variable pitohui (Pitohui
      kirhocephalus), are sometimes strikingly patterned and, in certain portions of
      their geographical ranges, both species share a nearly identical colour pattern,
      whereas in other areas they do not. Mullerian mimicry (the mutual resemblance of
      two chemically defended prey species) is common in some other animal groups and
      Pitohui birds have been suggested as one of the most likely cases in birds. Here,
      we examine pitohui plumage evolution in the context of a well-supported molecular
      phylogeny and use a maximum likelihood approach to test for convergent evolution
      in coloration. We show that the 'mimetic' phenotype is ancestral to both species
      and that the resemblance in most races is better explained by a shared ancestry.
      One large clade of P. kirhocephalus lost this mimetic phenotype early in their
      evolution and one race nested deep within this clade appears to have re-evolved
      this phenotype. These latter findings are consistent with the hypothesis that
      Mullerian mimicry is driving the evolution for a similar colour pattern between
      P. dichrous, but only in this one clade of P. kirhocephalus

PMID- 11571041
TI  - Mutually exclusive muscle designs: the power output of the locomotory and sonic
      muscles of the oyster toadfish (Opsanus tau).
AB  - Animals perform a vast array of motor activities. Although it has generally been
      accepted that muscles are well suited to the function that they must perform,
      specialization for performing one function may compromise their ability for
      carrying out another. We examined this principle in the toadfish muscular system:
      slow-twitch red and fast-twitch white myotomal muscles are used for powering
      swimming at relatively low frequencies, while the superfast swimbladder muscle
      powers mating calls by contracting at 100 Hz. We measured muscle power output
      over a wide range of frequencies. The red and white locomotory muscles could not
      generate power over ca. 2.2 and 12 Hz, respectively and, hence, could not power
      sound production. In contrast, the swimbladder muscle has many specializations
      that permit it to generate power at frequencies in excess of 100 Hz. However,
      these specializations drastically reduce its power output at low frequencies: the
      swimbladder muscle generated only one-twentieth of the power of the red muscle
      and one-seventh of the power of the white muscle at the frequencies used during
      swimming. To generate the same total power needed for swimming would require
      unfeasibly large amounts of swimbladder muscle that could not fit into the fish.
      Hence, the designs of the swimbladder and locomotory muscles are mutually
      exclusive.

PMID- 11571043
TI  - Reproductive investment in pre-industrial humans: the consequences of offspring
      number, gender and survival.
AB  - The number and gender of offspring produced in a current reproductive event can
      affect a mother's future reproductive investment and success. I studied the
      subsequent reproductive outcome of pre-industrial (1752-1850) Finnish mothers
      producing twins versus singletons of differing gender. I predicted that giving
      birth to and raising twins instead of singletons, and males instead of females,
      would incur a greater reproductive effort and, hence, lead to larger future
      reproductive costs for mothers. I compared the mothers' likelihood of reproducing
      again in the future, their time to next reproduction and the gender and survival
      of their next offspring. I found that mothers who produced twins were more likely
      to stop breeding or breed unsuccessfully in the future as compared with women of
      a similar age and reproductive history who produced a same-gender singleton
      child. As predicted, the survival and gender of the offspring produced modified
      the costs of reproduction for the mothers. Giving birth to and raising males
      generally appeared to be the most expensive strategy, but this effect was only
      detected in mothers who produced twins and, thus, suffering from higher overall
      costs of reproduction.

PMID- 11571044
TI  - Mechanical and metabolic determinants of the preferred step width in human
      walking.
AB  - We studied the selection of preferred step width in human walking by measuring
      mechanical and metabolic costs as a function of experimentally manipulated step
      width (0.00-0.45L, as a fraction of leg length L). We estimated mechanical costs
      from individual limb external mechanical work and metabolic costs using open
      circuit respirometry. The mechanical and metabolic costs both increased
      substantially (54 and 45%, respectively) for widths greater than the preferred
      value (0.15-0.45L) and with step width squared (R(2) = 0.91 and 0.83,
      respectively). As predicted by a three-dimensional model of walking mechanics,
      the increases in these costs appear to be a result of the mechanical work
      required for redirecting the centre of mass velocity during the transition
      between single stance phases (step-to-step transition costs). The metabolic cost
      for steps narrower than preferred (0.10-0.00L) increased by 8%, which was
      probably as a result of the added cost of moving the swing leg laterally in order
      to avoid the stance leg (lateral limb swing cost). Trade-offs between the step-to
      step transition and lateral limb swing costs resulted in a minimum metabolic cost
      at a step width of 0.12L, which is not significantly different from foot width
      (0.11L) or the preferred step width (0.13L). Humans appear to prefer a step width
      that minimizes metabolic cost.

PMID- 11571045
TI  - RNA replication kinetics, genetic polymorphism and selection in the case of the
      hepatitis C virus.
AB  - We show in a simple theoretical quasispecies model that the replication dynamics
      of hepatitis C virus and a related model-system, the bovine viral diarrhoea
      virus, result in an effective reduction of RNA templates in infected cells. Viral
      fitness does not translate directly into RNA sequence replication efficiency, and
      hence the abundance of the viral master sequences diminishes over time. Our
      results suggest that genes not involved in RNA replication accumulate mutations
      over time because they do not undergo selection during this phase. The selection
      of viral RNA occurs not only during replication but also during the ensuing
      stages of the viral life cycle: (i) envelopment of viral RNA and (ii) successful
      infection of other cells, which also requires functionality of non-replicative
      genes. In particular, viral fitness requires the ability of the genome to encode
      structural proteins which do not encounter selective pressure during RNA
      replication. We conclude by discussing the potential value of antiviral drugs
      which inhibit selection on parts of the viral genome.

PMID- 11571046
TI  - Adjustment of offspring sex ratios in relation to the availability of resources
      for philopatric offspring in the common brushtail possum.
AB  - The local-resource-competition hypothesis predicts that where philopatric
      offspring compete for resources with their mothers, offspring sex ratios will be
      biased in favour of the dispersing sex. This should produce variation in sex
      ratios between populations in relation to differences in the availability of
      resources for philopatric offspring. However, previous tests of local resource
      competition in mammals have used indirect measures of resource availability and
      have focused on sex-ratio variation between species or individuals rather than
      between local populations. Here, we show that the availability of den sites
      predicts the offspring sex ratio in populations of the common brushtail possum.
      Female possums defend access to dens, and daughters, but not sons, occupy dens
      within their mother's range. However, the abundances of possums in our study
      areas were determined principally by food availability. Consequently, in food
      rich areas with a high population density, the per-capita availability of dens
      was low, and the cost of having a daughter should have been high. This cost was
      positively correlated with male bias in the sex ratio at birth. Low per capita
      availability of dens was correlated with male bias in the sex ratio at birth.

PMID- 11571047
TI  - Evidence that helping at the nest does not result in territory inheritance in the
      Seychelles warbler.
AB  - In an environment that has a shortage of territories, helping to rear younger
      siblings ('alloparenting') is proposed to facilitate territory acquisition in two
      ways: (i) through group augmentation that leads to an increase of the territory
      with subsequent partial inheritance (budding); and (ii) through site dominance
      that leads to greater success when competing for the natal or a nearby territory
      after the death of the territory owner (complete territory inheritance). Most
      young Seychelles warbler (Acrocephalus sechellensis) males either show
      alloparenting or budding behaviour. Future budders had significantly more
      aggressive interactions with neighbours and assisted their parents more with
      territory defence than similarly aged future alloparents or non-helpers. This led
      to an increase of the natal territory of future budders before actual budding
      took place, whereas the natal territories of future alloparents remained constant
      in size. Alloparents never became budders and vice versa, refuting partial
      inheritance as an advantage of alloparenting. Natural male breeding vacancies
      were never inherited by alloparents born on vacant or other territories, but were
      inherited by budders born on the vacant territory or, if these were absent,
      predominantly by budders from neighbouring territories. We offer explicit
      experimental evidence against the 'helping at the nest to inherit' hypothesis.
      Experimentally created male breeding vacancies, with both a male alloparent and a
      similarly aged sibling budder present simultaneously in the vacant territory,
      were filled by budders only. Site dominance over territory inheritance is linked
      to budding and not to alloparenting.

PMID- 11571048
TI  - Songbird cheaters pay a retaliation cost: evidence for auditory conventional
      signals.
AB  - Conventional signals impose costs on senders through receiver retaliation rather
      than through investment in signal production. While several visual conventional
      signals have been described (mainly 'badges of status'), acoustic examples are
      rare; however, several aspects of repertoire use in songbirds are potential
      candidates. We performed interactive playback experiments to determine whether
      song-type matches (responding to a song with the same song type), repertoire
      matches (responding to a song with a different song type, but one in the
      repertoires of both singers) and unshared song types serve as conventional
      signals during male-male territorial interactions in banded wrens, Thryothorus
      pleurostictus. Our results demonstrate that these three signals incite varying
      levels of receiver aggression: song-type matches induce faster approach than do
      repertoire matches, and repertoire matches induce faster approach than do
      unshared song types. Production costs do not differ, while the receiver response
      does. Because territorial banded wrens approach opponents who signal
      aggressively, such opponents risk attack. This system will punish and prevent
      cheaters, as weak males signalling aggression will be subject to escalation by
      stronger or more-motivated opponents.

PMID- 11571049
TI  - The influence of parental relatedness on reproductive success.
AB  - The relationship between fitness and parental similarity has been dominated by
      studies of how inbreeding depression lowers fecundity in incestuous matings. A
      widespread implicit assumption is that adult fitness (reproduction) of
      individuals born to parents who are not unusually closely related is more or less
      equal. Examination of three long-lived vertebrates, the long-finned pilot whale,
      the grey seal and the wandering albatross reveals significant negative
      relationships between parental similarity and genetic estimates of reproductive
      success. This effect could, in principle, be driven by a small number of low
      quality, inbred individuals. However, when the data are partitioned into
      individuals with above average and below average parental similarity, we find no
      evidence that the slopes differ, suggesting that the effect is more or less
      similar across the full range of parental similarity values. Our results thus
      uncover a selective pressure that favours not only inbreeding avoidance, but also
      the selection of maximally dissimilar mates.

PMID- 11571050
TI  - Mortality plateaus and directionality theory.
AB  - Recent large scale studies of senescence in animals and humans have revealed
      mortality rates that levelled off at advanced ages. These empirical findings are
      now known to be inconsistent with evolutionary theories of senescence based on
      the Malthusian parameter as a measure of fitness. This article analyses the
      incidence of mortality plateaus in terms of directionality theory, a new class of
      models based on evolutionary entropy as a measure of fitness. We show that the
      intensity of selection, in the context of directionality theory, is a convex
      function of age, and we invoke this property to predict that in populations
      evolving under bounded growth constraints, evolutionarily stable mortality
      patterns will be described by rates which abate with age at extreme ages. The
      explanatory power of directionality theory, in contrast with the limitations of
      the Malthusian model, accords with the claim that evolutionary entropy, rather
      than the Malthusian parameter, constitutes the operationally valid measure of
      Darwinian fitness.

PMID- 11571051
TI  - Complexity and fragility in ecological networks.
AB  - A detailed analysis of three species-rich ecosystem food webs has shown that they
      display skewed distributions of connections. Such graphs of interaction are, in
      fact, shared by a number of biological and technological networks, which have
      been shown to display a very high homeostasis against random removals of nodes.
      Here, we analyse the responses of these ecological graphs to both random and
      selective perturbations (directed against the most-connected species). Our
      results suggest that ecological networks are very robust against random removals
      but can be extremely fragile when selective attacks are used. These observations
      have important consequences for biodiversity dynamics and conservation issues,
      current estimations of extinction rates and the relevance and definition of
      keystone species.

PMID- 11571052
TI  - A new Triassic procolophonoid reptile and its implications for procolophonoid
      survivorship during the Permo-Triassic extinction event.
AB  - A reptile specimen from the Lystrosaurus Assemblage Zone of the Beaufort Group,
      lowermost Triassic of South Africa, represents a new procolophonoid parareptile.
      Sauropareion anoplus gen. et sp. nov. is identified as the sister taxon of
      Procolophonidae in a phylogenetic analysis of procolophonoids. Stratigraphic
      calibration of the most parsimonious tree reveals that four of the six
      procolophonoid lineages originating in the Permian Period extended into the
      succeeding Triassic Period. This relatively high taxic survivorship (67%) across
      the Permo-Triassic boundary strongly suggests that procolophonoids were little if
      at all affected by the mass extinction event that punctuated the end of the
      Palaeozoic Era (ca. 251 million years ago).

PMID- 11571053
TI  - Demography and population dynamics of the mouse opossum (Thylamys elegans) in
      semi-arid Chile: seasonality, feedback structure and climate.
AB  - Here we present, to the authors' knowledge for the very first time for a small
      marsupial, a thorough analysis of the demography and population dynamics of the
      mouse opossum (Thylamys elegans) in western South America. We test the relative
      importance of feedback structure and climatic factors (rainfall and the Southern
      Oscillation Index) in explaining the temporal variation in the demography of the
      mouse opossum. The demographic information was incorporated into a stage
      structured population dynamics model and the model's predictions were compared
      with observed patterns. The mouse opossum's capture rates showed seasonal (within
      year) and between-year variability, with individuals having higher capture rates
      during late summer and autumn and lower capture rates during winter and spring.
      There was also a strong between-year effect on capture probabilities. The
      reproductive (the fraction of reproductively active individuals) and recruitment
      rates showed a clear seasonal and a between-year pattern of variation with the
      peak of reproductive activity occuring during winter and early spring. In
      addition, the fraction of reproductive individuals was positively related to
      annual rainfall, while population density and annual rainfall positively
      influenced the recruitment rate. The survival rates were negatively related to
      annual rainfall. The average finite population growth rate during the study
      period was estimated to be 1.011 +/- 0.0019 from capture-recapture estimates.
      While the annual growth rate estimated from the seasonal linear matrix models was
      1.026, the subadult and adult survival and maturation rates represent between 54%
      (winter) and 81% (summer) of the impact on the annual growth rate.

PMID- 11571054
TI  - Relevance of visual cues for orientation at familiar sites by homing pigeons: an
      experiment in a circular arena.
AB  - Whether pigeons use visual landmarks for orientation from familiar locations has
      been a subject of debate. By recording the directional choices of both anosmic
      and control pigeons while exiting from a circular arena we were able to assess
      the relevance of olfactory and visual cues for orientation from familiar sites.
      When the birds could see the surroundings, both anosmic and control pigeons were
      homeward oriented. When the view of the landscape was prevented by screens that
      surrounded the arena, the control pigeons exited from the arena approximately in
      the home direction, while the anosmic pigeons' distribution was not different
      from random. Our data suggest that olfactory and visual cues play a critical, but
      interchangeable, role for orientation at familiar sites.

PMID- 11571055
TI  - The energetic grooming costs imposed by a parasitic mite (Spinturnix myoti) upon
      its bat host (Myotis myotis).
AB  - Parasites often exert severe negative effects upon their host's fitness. Natural
      selection has therefore prompted the evolution of anti-parasite mechanisms such
      as grooming. Grooming is efficient at reducing parasitic loads in both birds and
      mammals, but the energetic costs it entails have not been properly quantified. We
      measured both the energetic metabolism and behaviour of greater mouse-eared bats
      submitted to three different parasite loads (no, 20 and 40 mites) during whole
      daily cycles. Mites greatly affected their time and energy budgets. They caused
      increased grooming activity, reduced the overall time devoted to resting and
      provoked a dramatic shortening of resting bout duration. Correspondingly, the
      bats' overall metabolism (oxygen consumption) increased drastically with parasite
      intensity and, during the course of experiments, the bats lost more weight when
      infested with 40 rather than 20 or no parasites. The short-term energetic
      constraints induced by anti-parasite grooming are probably associated with long
      term detrimental effects such as a decrease in survival and overall reproductive
      value.

PMID- 11571056
TI  - Tobacco--the once and future addiction.

PMID- 11571057
TI  - No switching off the camera: how Addiction will respond to infringements of
      ethical publishing expectation.

PMID- 11571058
TI  - Conversation with Klaus Makela.

PMID- 11571059
TI  - In defence of the British system of injectable diamorphine prescription.

PMID- 11571060
TI  - Acute subjective and physiological responses to smoking in adolescents.
AB  - AIMS: To determine the topography of cigarette smoking and the subjective and
      physiological effects of abstinence and nicotine in adolescents who smoke on a
      daily versus a non-daily basis. DESIGN: Repeated measures experiment, non
      blinded, involving a single test session. SETTING: Human psychopharmacology
      laboratory. PARTICIPANTS: Twenty-one daily and 21 non-daily adolescent cigarette
      smokers (21 females; 21 males; age 13-18 years) with life-time use greater than
      10 cigarettes, responding to radio and print advertisements. INTERVENTION:
      Overnight abstinence from cigarettes followed by smoking of a single cigarette
      furnished by the participant at test. MEASUREMENTS: The Fagerstrom Test for
      Nicotine Dependence, saliva nicotine and cotinine, expired air carbon monoxide
      (CO), heart rate (HR), self-report scales and smoking topography. Most
      measurements were performed before and after smoking. FINDINGS: Saliva nicotine,
      CO and HR increased, and self-reported intention and desire to smoke decreased,
      after smoking (p < 0.001). Fagerstrom scores indicated greater dependence and
      desire to smoke in daily than in non-daily smokers. HR increased substantially
      over pre-smoking levels in both groups. Puff topography did not differ between
      the groups, although collectively these participants appeared to take smaller and
      more puffs than adult smokers tested under similar conditions. CONCLUSION: This
      study provides initial evidence that adolescent cigarette smokers self-administer
      physiologically active doses of nicotine very early in their smoking careers.
      Nicotine dependence in adolescents appears to be a function of the current
      frequency of cigarette use, and subjective-behavioral consequences of abstinence
      and smoking are evident even in non-daily smokers.

PMID- 11571061
TI  - A multi-dimensional analysis of cue-elicited craving in heavy smokers and tobacco
      chippers.
AB  - AIMS: This research examined the performance of a broad range of measures posited
      to relate to smoking craving. DESIGN: Heavy smokers and tobacco chippers, who
      were either deprived of smoking or not for 7 hours, were exposed to both smoking
      (a lit cigarette) and control cues. PARTICIPANTS: Smokers not currently
      interested in trying to quit smoking (n = 127) were recruited. Heavy smokers (n =
      67) averaged smoking at least 21 cigarettes/day and tobacco chippers (n = 60)
      averaged 1-5 cigarettes on at least 2 days/week. MEASUREMENTS: Measures included
      urge rating scales and magnitude estimations, a rating of affective valence, a
      behavioral choice task that assessed perceived reinforcement value of smoking,
      several smoking-related judgement tasks and a measure of cognitive resource
      allocation. FINDINGS: Results indicated that both deprivation state and smoker
      type tended to affect responses across these measurement domains. CONCLUSIONS:
      Findings support the use of several novel measures of craving-related processes
      in smokers.

PMID- 11571062
TI  - Comparison of methadone and high dosage buprenorphine users in French care
      centres.
AB  - AIMS: In France, maintenance programmes for opiate users were adopted later than
      in other countries. Two maintenance treatments are available: methadone is only
      delivered in specialized centres while high dosage (HD) buprenorphine can be
      prescribed by all general practitioners and in specialized centres. The aim of
      this study was to compare the socio-demographic profiles, the practices and drug
      consumption patterns of the two groups attending specialized centres.
      METHODOLOGY: The Oppidum Programme (observation of illegal drugs and misuse of
      psychotropic medications), a multi-centric survey, surveys drug-dependent
      subjects attending specialized care centres throughout France annually. Data were
      collected by questionnaire on socio-demographic variables and drug use during the
      preceding week. RESULTS: During October 1998, 46 centres took part in the survey.
      The methadone group (n = 424) was older, with a better economic situation; 16%
      used cocaine regularly. The HD buprenorphine group (n = 616) consumed more heroin
      (12% vs. 8%) and engaged in more misuse, such as intravenous use, illicit
      acquisitions or irregular consumption. These practices were more frequent for
      patients consuming the drug "outwith protocol" or for patients obtaining the drug
      from a general practitioner. CONCLUSION: Our results suggest that patterns of
      consumption of methadone and buprenorphine are different in several respects:
      concomitant use of licit or illicit psychoactive substances, route of
      administration, and illegal acquisition. They also suggest that the behaviours of
      maintenance treatment users depend less on the nature of the maintenance drug
      (methadone or high dosage buprenorphine), than the nature of the delivery and
      monitoring practices.

PMID- 11571063
TI  - The relationship between suicide and heroin overdose among methadone maintenance
      patients in Sydney, Australia.
AB  - AIMS: To examine the relationship between attempted suicide and non-fatal heroin
      overdose among methadone maintenance patients. DESIGN: Cross-sectional survey.
      SETTING: Sydney, Australia. PARTICIPANTS: Two hundred and twenty-three methadone
      maintenance patients. FINDINGS: Forty per cent of participants reported a history
      of at least one suicide attempt. Females were significantly more likely than
      males to have attempted suicide (50% vs. 31%), and to have done so on more than
      one occasion (28% vs. 15%). There was a large difference between males and
      females in the onset of attempted suicide. Females reported an initial attempt,
      on average, 6 years earlier than males (18.3 vs. 24.7 years), and were
      significantly more likely than males to have attempted suicide prior to the onset
      of heroin use (69% vs. 11%). While heroin overdose was common among the sample
      (66%), the most common methods employed for suicide attempts were overdose of a
      non-opioid drug (21%) and slitting of wrists (20%). A deliberate heroin overdose
      as a means of attempted suicide was reported by 10% of participants. Heroin
      overdoses appeared overwhelmingly to be accidental. Ninety-two per cent of those
      who had overdosed reported that their most recent overdose was accidental.
      CONCLUSIONS: Attempted suicide presents a major clinical problem to staff at drug
      treatment programmes, but one distinct from heroin overdose. While both overdose
      and suicide present increasing clinical problems, they are separate problems, and
      require different responses.

PMID- 11571064
TI  - Mortality among problem drug users in Rome: an 18-year follow-up study, 1980-97.
AB  - AIM: To analyse overall and cause-specific mortality among problem drug users
      (PDUs) attending treatment centres in Rome and to evaluate differences in
      mortality between genders. METHODS: A cohort of 11 432 PDUs entering treatment in
      Rome between 1980 and 1995 was enrolled and followed-up as of May 31, 1997.
      Directly standardized mortality rates and standardized mortality ratios (SMRs)
      and their 95% confidence intervals (95% CI) were calculated. RESULTS: The study
      population included mainly males (82%), heroin users (92%) and had a mean age of
      26.6 (SD 5.9) at enrollment. At the end of the study period 1734 deaths were
      observed. Overall mortality rates began to increase in 1985-86 and decreased
      slightly afterwards. AIDS mortality peaked in 1991-92 (13.2/1000) and fell in the
      following years. A slight decrease in overdose mortality also occurred after 1989
      90. Mortality for causes other than AIDS and overdose remained high and
      relatively steady for the whole study period. Women showed higher mortality rates
      for AIDS but lower mortality rates for overdose than males. Overall mortality
      risk among drug addicts was about 15 times higher compared to the general
      population of the same age among men, and 38 times higher among women.
      CONCLUSIONS: AIDS mortality among drug addicts began to decrease earlier than
      expected; the decrease was particularly significant in the period 1993-94 for
      both sexes. Afterwards a continuous but slight decrease was observed among males
      only. Even though overdose mortality has also decreased slightly in recent years,
      we still observe high mortality levels for both overdose and all other causes.
      These findings suggest that interventions directed specifically towards the
      reduction of baseline mortality are still needed.

PMID- 11571065
TI  - A comparison of different methods for estimating the prevalence of problematic
      drug misuse in Great Britain.
AB  - AIMS: The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) has
      produced methodological guidelines for national drug prevalence estimation. This
      paper pilots the methods to estimate prevalence for Great Britain and provides a
      commentary on the methods and resulting estimates. DESIGN: Three types of
      methodology were used to estimate prevalence: (a) the multiple indicator (MI)
      method, (b) multipliers applied to (i) drug-treatment records (ii) HIV estimates
      and (iii) mortality statistics and (c) the British/Scottish Crime Surveys.
      SETTING: England, Scotland and Wales. PARTICIPANTS: Aggregated data on people
      recorded on databases and respondents in household surveys. MEASUREMENTS:
      Prevalence estimates of different forms of problematic drug use. FINDINGS: The
      estimates are 161,133 (range: 120,850-241,700) for people at risk of mortality
      due to drug overdose; 161,000-169,000 for people who have ever injected drugs;
      202,000 (range: 162,000-244,000) problem opiate users and 268,000 problem drug
      users (all types). CONCLUSIONS: The multiple indicator method offers a
      comprehensive approach to estimating the prevalence of problematic drug use in
      the United Kingdom. Simple multiplier methods and household surveys also provide
      a range of estimates corresponding to different types of drug use in the United
      Kingdom. The current study suggests that previous national estimates of 100,000
      200,000 were conservative. The new estimate of 161,000-266,000 should enable a
      more focused response. For further development of this method, reliable and
      timely estimates of anchor points are required for specific geographical areas
      such as cities or Drug Action Teams (DAT), as well as routine aggregation of drug
      indicators for these areas.

PMID- 11571066
TI  - Evaluation of the Adolescent Drug Abuse Diagnosis instrument in a Swiss sample of
      drug abusers.
AB  - OBJECTIVE: The aim of this study was to evaluate a French language version of the
      Adolescent Drug Abuse Diagnosis (ADAD) instrument in a Swiss sample of adolescent
      illicit drug and/or alcohol users. PARTICIPANTS AND SETTING: The participants in
      the study were 102 French-speaking adolescents aged 13-19 years who fitted the
      criteria of illicit drug or alcohol use (at least one substance--except tobacco-
      once a week during the last 3 months). They were recruited in hospitals,
      institutions and leisure places. Procedure. The ADAD was administered
      individually by trained psychologists. It was integrated into a broader protocol
      including alcohol and drug abuse DSM-IV diagnoses, the BDI-13 (Beck Depression
      Inventory), life events and treatment trajectories. RESULTS: The ADAD appears to
      show good inter-rater reliability; the subscales showed good internal coherence
      and the correlations between the composite scores and the severity ratings were
      moderate to high. Finally, the results confirmed good concurrent validity for
      three out of eight ADAD dimensions. CONCLUSIONS: The French language version of
      the ADAD appears to be an adequate instrument for assessing drug use and
      associated problems in adolescents. Despite its complexity, the instrument has
      acceptable validity, reliability and usefulness criteria, enabling international
      and transcultural comparisons.

PMID- 11571067
TI  - Adverse outcomes of alcohol use in adolescents.
AB  - AIMS: To compare the occurrence of behaviours occurring under the influence of
      alcohol in 16-17-year-olds and determine associated risk factors for the
      different behaviours. DESIGN/SETTING: Cross-sectional survey administered by
      laptop computers in secondary schools across the state of Victoria, Australia.
      MEASUREMENT/FINDINGS: The participation rate was 79%. Seventy per cent of
      participants drank alcohol; 17% of drinkers reported alcohol-related violence
      (accidents or injuries) and 15% reported problems relating to sex under the
      influence of alcohol (having sex and later regretting it or having had unsafe
      sex) in the previous 12 months. Males were more likely to report alcohol-related
      violence (20% compared to 14% females). Almost one in 10 young people reported
      having sex while under the influence of alcohol and later regretting it and 10%
      reported having had unsafe sex. There were no significant gender differences in
      the reporting rates of alcohol-related sexual risk taking (prop. cum. OR 1.1, 95%
      CI 0.68-1.9). For alcohol-related injuries, strong independent associations were
      found with dose of alcohol consumed (prop. cum. OR 2.3, 95% CI 1.3-4.0),
      frequency of alcohol consumption (prop. cum. OR 2.7, 95% CI 0.94-7.5), antisocial
      behaviour (prop. cum. OR 2.4, 95% CI 1.4-4.1) and peer drinking (prop. cum. OR
      3.3, 95% CI 1.4-8.1). For alcohol-related sexual risk-taking, psychiatric
      morbidity (prop. cum. OR 4.1, 95% CI 1.9-9.0) and high frequency of alcohol
      consumption (prop. cum. OR 2.0, 95% CI 0.87-4.6) had strong independent
      associations. CONCLUSIONS: Physical injury and high-risk sexual behaviour under
      the influence of alcohol are common in teenagers. Alcohol-related physical injury
      appears closely related to patterns of alcohol consumption whereas alcohol
      related sexual risk-taking is most closely associated with symptoms of depression
      and anxiety.

PMID- 11571068
TI  - Helping the female partners of men abusing alcohol: a comparison of three
      treatments.
AB  - AIM: To evaluate the effectiveness of three approaches to assisting the female
      partners of male problem drinkers with the stress imposed by the male's drinking.
      DESIGN: Participants were assigned randomly via random number tables to one of
      three treatment conditions: supportive counselling, stress management or alcohol
      focused couples therapy. SETTING: The intervention took place at the Behaviour
      Research and Therapy Centre (BRTC), The University of Queensland. This research
      and training centre offers outpatient psychology services to the community.
      PARTICIPANTS: Sixty-one married women whose husbands drank heavily. Participants
      reported protracted alcohol problems, severe impact of alcohol on social
      functioning and severe marital distress. MEASUREMENT: The women's stress, alcohol
      consumption by the male, and relationship functioning were assessed at pre- and
      post-treatment and at 6-month follow-up. INTERVENTIONS: All three treatments
      involved 15 1-hour sessions with the woman. In the alcohol-focused couple
      therapy, attempts were made to engage the man in these sessions. RESULTS:
      Contrary to our predictions, there were few differences between the treatments.
      All three treatments were associated with reductions in the women's reported
      stress, with trends for somewhat greater reduction in the women's stress in the
      stress management and alcohol-focused couples therapy conditions than for
      supportive counselling. None of the treatments produced clinically significant
      reductions in men's drinking or relationship distress. CONCLUSION: The treatments
      ease stresses and burden but do not improve drinking or relationships. Limited
      power in the design restricted the capacity to detect differential treatment
      effects.

PMID- 11571069
TI  - ILSI and the tobacco industry connection.

PMID- 11571071
TI  - Numerical comparison of several approximations of the word count distribution in
      random sequences.
AB  - The exact distribution of word counts in random sequences and several
      approximations have been proposed in the past few years. The exact distribution
      has no theoretical limit but may require prohibitive computation time. On the
      other hand, approximate distributions can be rapidly calculated but, in practice,
      are only accurate under specific conditions. After making a survey of these
      distributions, we compare them according to both their accuracy and computational
      cost. Rules are suggested for choosing between Gaussian approximations, compound
      Poisson approximation, and exact distribution. This work is illustrated with the
      detection of exceptional words in the phage Lambda genome.

PMID- 11571072
TI  - On the complexity of positional sequencing by hybridization.
AB  - In sequencing by hybridization (SBH), one has to reconstruct a sequence from its
      l-long substrings. SBH was proposed as an alternative to gel-based DNA sequencing
      approaches, but in its original form the method is not competitive. Positional
      SBH (PSBH) is a recently proposed enhancement of SBH in which one has additional
      information about the possible positions of each substring along the target
      sequence. We give a linear time algorithm for solving PSBH when each substring
      has at most two possible positions. On the other hand, we prove that the problem
      is NP-complete if each substring has at most three possible positions. We also
      show that PSBH is NP-complete if the set of allowed positions for each substring
      is an interval of length k and provide a fast algorithm for the latter problem
      when k is bounded.

PMID- 11571073
TI  - Exact distribution for the local score of one i.i.d. random sequence.
AB  - Let X(1)...X(n) be a sequence of i.i.d. positive or negative integer-valued
      random variables and H(n) = max(0 < or = i < or = j < or = n)(X(i) +...+ X(j)) be
      the local score of the sequence. The exact distribution of H(n) is obtained using
      a simple Markov chain. This result is applied to the scoring of DNA and protein
      sequences in molecular biology.

PMID- 11571074
TI  - Rate matrices for analyzing large families of protein sequences.
AB  - We propose and study a new approach for the analysis of families of protein
      sequences. This method is related to the LogDet distances used in phylogenetic
      reconstructions; it can be viewed as an attempt to embed these distances into a
      multidimensional framework. The proposed method starts by associating a Markov
      matrix to each pairwise alignment deduced from a given multiple alignment. The
      central objects under consideration here are matrix-valued logarithms L of these
      Markov matrices, which exist under conditions that are compatible with fairly
      large divergence between the sequences. These logarithms allow us to compare data
      from a family of aligned proteins with simple models (in particular, continuous
      reversible Markov models) and to test the adequacy of such models. If one
      neglects fluctuations arising from the finite length of sequences, any continuous
      reversible Markov model with a single rate matrix Q over an arbitrary tree
      predicts that all the observed matrices L are multiples of Q. Our method exploits
      this fact, without relying on any tree estimation. We test this prediction on a
      family of proteins encoded by the mitochondrial genome of 26 multicellular
      animals, which include vertebrates, arthropods, echinoderms, molluscs, and
      nematodes. A principal component analysis of the observed matrices L shows that a
      single rate model can be used as a rough approximation to the data, but that
      systematic deviations from any such model are unmistakable and related to the
      evolutionary history of the species under consideration.

PMID- 11571075
TI  - Detection of recombination in DNA multiple alignments with hidden Markov models.
AB  - Conventional phylogenetic tree estimation methods assume that all sites in a DNA
      multiple alignment have the same evolutionary history. This assumption is
      violated in data sets from certain bacteria and viruses due to recombination, a
      process that leads to the creation of mosaic sequences from different strains
      and, if undetected, causes systematic errors in phylogenetic tree estimation. In
      the current work, a hidden Markov model (HMM) is employed to detect recombination
      events in multiple alignments of DNA sequences. The emission probabilities in a
      given state are determined by the branching order (topology) and the branch
      lengths of the respective phylogenetic tree, while the transition probabilities
      depend on the global recombination probability. The present study improves on an
      earlier heuristic parameter optimization scheme and shows how the branch lengths
      and the recombination probability can be optimized in a maximum likelihood sense
      by applying the expectation maximization (EM) algorithm. The novel algorithm is
      tested on a synthetic benchmark problem and is found to clearly outperform the
      earlier heuristic approach. The paper concludes with an application of this
      scheme to a DNA sequence alignment of the argF gene from four Neisseria strains,
      where a likely recombination event is clearly detected.

PMID- 11571076
TI  - Modeling genetic regulatory dynamics in neural development.
AB  - We model genetic regulatory networks in the framework of continuous-time
      recurrent networks. The network parameters are determined from gene expression
      level time series data using genetic algorithms. We have applied the method to
      expression data from the development of rat central nervous system, where the
      active genes cluster into four groups, within which the temporal expression
      patterns are similar. The data permit us to identify approximately the
      interactions between these groups of genes. We find that generally a single time
      series is of limited value in determining the interactions in the network, but
      multiple time series collected in related tissues or under treatment with
      different drugs can fix their values much more precisely.

PMID- 11571077
TI  - Unfolding of microarray data.
AB  - The use of DNA microarrays for the analysis of complex biological samples is
      becoming a mainstream part of biomedical research. One of the most commonly used
      methods compares the relative abundance of mRNA in two different samples by
      probing a single DNA microarray simultaneously. The simplicity of this concept
      sometimes masks the complexity of capturing and processing microarray data. On
      the basis of the analysis of many of our microarray experiments, we identified
      the major causes of distortion of the microarray data and the sources of noise.
      In this study, we provide a systematic statistical approach for extraction of
      true expression ratios from raw microarray data, which we describe as an
      unfolding process. The results of this analysis are presented in the form of a
      model describing the relationship between the measured fluorescent intensities
      and the concentrations of mRNA transcripts. We developed and tested several
      algorithms for inference of the model parameters for the microarray data. Special
      emphasis is given to the statistical robustness of these algorithms, in
      particular resistance to outliers. We also provide methods for measurement of
      noise and reproducibility of the microarray experiments.

PMID- 11571079
TI  - A comparative study of teleconsultations versus face-to-face consultations.
AB  - We compared the diagnoses made by one dermatologist via telemedicine with those
      of another dermatologist made in a face-to-face consultation. The patients first
      underwent a teledermatology consultation and then a face-to-face consultation. A
      general practitioner was present with the patient in the videoconference studio.
      Videoconferencing equipment connected at 384 kbit/s was used. The doctor-patient
      relationship and the satisfaction of the patients and dermatologists in the two
      settings were assessed, as well as technical conditions during the
      videoconferences. There were 121 patients, with a mean age of 40 years (range 17
      82 years). There was a high degree of concordance between the two sets of
      diagnoses, with 72% complete agreement and 14% partial agreement between the two
      dermatologists. A total of 116 patients (96% of those included) completed a
      questionnaire. Both the patients and the dermatologists were in general satisfied
      with the videoconferences. Videoconferencing with a participating general
      practitioner may be useful in dermatology, but the technique should be used only
      for selected patients.

PMID- 11571078
TI  - Telehealth and the diagnosis and management of cardiac disease.
AB  - The financial and personal burden of chronic cardiac disease is high. Costs are
      likely to increase over the next few decades. Promising applications of
      telehealth have appeared in the diagnosis and management of cardiac disease and
      there are indications that telehealth services can improve the management of
      chronic cardiac disease as well as extend services to remote and rural
      populations. Telehealth has been applied to the capture of symptoms of cardiac
      disease with electrocardiography and echocardiography, to the management and
      rehabilitation of recently discharged patients, and in peer-to-peer consultation
      where remote expertise can facilitate diagnosis. Telehealth promises cost
      reductions in service delivery, although there is a need for properly controlled
      cost-effectiveness trials to underpin telehealth with a firm evidence base.

PMID- 11571080
TI  - Videoconferencing in the Queensland health service.
AB  - Videoconferencing was introduced in the Queensland health service in 1995. By the
      end of 1999, there were more than 150 videoconferencing units in health
      facilities around the state. Six audits of videoconferencing usage were conducted
      using similar methodology at six-month intervals from November 1997 to May 2000.
      Between November 1997 and November 1999, the number of calls more than doubled,
      from 566 to 1378. Hours of usage almost trebled, from 671 to 1724. The average
      duration of calls remained similar, at about 1 h 12 min. The proportion of calls
      involving more than two sites (multipoint videoconferences) increased from 44% to
      65%. The majority of the activity was for education (including training).
      Videoconferencing was also used for administration and clinical care. Mental
      health staff were the heaviest users, but use by health professionals from other
      specialty areas increased during the study period. The Queensland health service
      has realized a number of important benefits from telehealth.

PMID- 11571081
TI  - Telephone advice nursing--callers' experiences.
AB  - We studied telephone callers' experiences of contacting a medical call centre. A
      questionnaire was administered to 203 persons. It was completed by 144 (71%), of
      whom 81 (56%) chose to comment on their experience in the space provided. The
      comments were analysed using a qualitative method and were categorized as
      relating to either the practical or the emotional aspects of the call. Sixty-nine
      per cent of comments described a satisfactory experience. The unsatisfactory
      comments mostly concerned access problems. The callers emphasized the importance
      of receiving appropriate advice and being treated in a kindly manner. In
      addition, there were dimensions of security and insecurity in nearly all the
      categories. The findings highlight the telephone nurses' communication skills and
      their ability to deal with callers as individuals, to make them feel more secure.
      The selection, education and training of telephone nurses should place more
      emphasis on their supportive and communicative roles.

PMID- 11571082
TI  - Changes in the workplace with telemedicine.
AB  - The opinions of 110 emergency nurse practitioners (ENPs) practising telemedicine
      in 11 British minor injury units were sought using a questionnaire. There were 90
      respondents (82%). The respondents thought that, since telemedicine had been
      introduced, they had become more open to change (96%) and more ready to grasp
      opportunities (93%). They considered that they were more keen to learn new things
      (99%) and were better disposed to teaching others (90%). They adopted a more
      advisory and supportive role (80%), found the work environment more varied (83%)
      and were well disposed to teamwork (64%). The power balance with doctors had
      changed (86%) and doctors indulged in dialogue rather than direction (69%). The
      results suggest that although changes have started in the workplace, they have
      not been as dramatic as a previous study of patients had predicted.

PMID- 11571083
TI  - The effect of education on patients' willingness to participate in a telemedicine
      study.
AB  - We assessed the effect of previous education on patients' willingness to
      participate in a clinical study of telemedicine for hypertensive patients. The
      design was a cross-sectional study of adult patients arriving for appointments in
      a hypertension clinic. Of the 259 patients approached, 86% completed a baseline
      survey and were subsequently asked if they would be willing to participate in a
      one-year telemedicine study. One hundred and fifty patients (58%) agreed to
      participate. A stepwise logistic regression analysis was performed to assess the
      effect of level of education on willingness to participate, while controlling for
      potentially confounding variables. In the final model, only education remained
      significant. The odds ratio for non-participation of patients with high-school
      education or less was 3.6 (95% confidence interval 1.9-7.0). Educational status
      should be carefully considered when designing, implementing and interpreting
      telemedicine studies.

PMID- 11571084
TI  - Telemedicine in the Michigan Upper Peninsula region: an evaluation of the first
      five years.
AB  - A telemedicine network has operated in the Upper Peninsula (UP) region of
      Michigan since 1995. The Marquette General Health System (MGHS) is the tertiary
      hospital that provides telemedicine services to 14 surrounding rural health
      facilities and another seven clinics. In order to assess the state of
      telemedicine in the UP region and its potential for development, three main
      factors were assessed: organizational development, telemedicine activity and
      perceptions of the key players. Data were collected through interviews with five
      MGHS telemedicine staff, 10 physicians (five from the MGHS and five from
      surrounding rural areas), 13 of the 14 chief executive officers (CEOs) of the
      remote telemedicine sites and a survey of 21 telemedicine site coordinators. This
      information was analysed in order to outline job roles and responsibilities; to
      document the process of doing telemedicine; and to understand current policies
      and procedures. Telemedicine activity from 1995 to 1999 was analysed in terms of
      the purpose of the session. In 1999, a total of 515 telemedicine sessions were
      conducted, 323 being non-educational and 192 being educational. Most CEOs of the
      rural hospitals were interested in furthering their use of clinical telemedicine
      applications. The data also indicated a great need for education, particularly of
      the rural physicians. The overall view of those surveyed about MGHS's
      telemedicine programme was positive. Respondents were quick to compliment the
      staff whenever possible. New telemedicine staff have been employed, which will
      allow responsibilities to be reassigned in such a way as to create a more
      efficient system.

PMID- 11571085
TI  - Training in cognitive-behavioural therapy for mental health professionals: a
      pilot study of videoconferencing.
AB  - A foundation course in cognitive-behavioural therapy (CBT) was developed
      specifically for delivery via videoconferencing at 256 kbit/s. A two-part, 20
      week programme was evaluated at seven sites, with a total of 12 participants, in
      rural and remote Western Australia. Eleven of the participants completed a pre-
      and post-training knowledge test. There was a significant improvement in their
      knowledge of CBT after training. Ten participants also completed a satisfaction
      questionnaire. The majority were satisfied with the training they received and
      stated that the training had given them greater confidence in their ability to
      use CBT with their patients. This study lends support to the use of
      videoconferencing in the training of rural and remote mental health
      practitioners.

PMID- 11571086
TI  - The interdisciplinary management of cerebral haemorrhage using telemedicine--a
      case report from Nepal.

PMID- 11571087
TI  - Internet telephony offers new opportunities for telemedicine.

PMID- 11571089
TI  - Increasing funding for interdisciplinary research.

PMID- 11571090
TI  - Preventing congenital rubella syndrome (CRS) through vaccination of susceptible
      women of childbearing age.

PMID- 11571091
TI  - Toward optimal health: the experts discuss epilepsy. Interview by Jodi Godfrey
      Miller.

PMID- 11571092
TI  - Academic models of clinical care for women: the National Centers of Excellence in
      Women's Health.
AB  - Between 1996 and 1999, 18 academic health centers were awarded the designation of
      National Center of Excellence (CoE) in Women's Health by the Office on Women's
      Health within the Department of Health and Human Services and were provided with
      seed monies to develop model clinical services for women. Although the model has
      evolved in various forms, core characteristics that each nationally designated
      CoE has adopted include comprehensive, women-friendly, women-focused, women
      relevant, integrated, multidisciplinary care. The permanent success of these
      comprehensive clinical programs resides in the ability to garner support of
      leaders of the academic health centers who understand both the importance of
      multidisciplinary programs to the clinical care they provide women and the
      education they offer to the future providers of women's healthcare.

PMID- 11571093
TI  - A qualitative analysis of women's satisfaction with primary care from a panel of
      focus groups in the National Centers of Excellence in Women's Health.
AB  - Health issues unique to women and differences in healthcare experiences have
      recently gained attention as health plans and systems seek to extend and improve
      health promotion and disease prevention in the population. Successful efforts
      focused on enhancing quality of care will require information from the patient's
      perspective on how to improve such services to best support women's attempts to
      lead healthy and productive lives. The National Centers of Excellence in Women's
      Health program (CoE), sponsored by the Office on Women's Health within the
      Department of Health and Human Services, is based on an integrated model uniting
      research, training, healthcare, and community education and outreach. To examine
      women's concept and definitions of healthcare quality, 18 focus groups comprising
      137 women were conducted nationwide on experiences and attributes of healthcare
      that women value in primary care. Following the focus groups, a woman-focused
      healthcare satisfaction instrument was developed for the purpose of assessing and
      improving healthcare delivery. We describe the qualitative results of the focus
      group study.

PMID- 11571094
TI  - Cost-effectiveness of prenatal screening for postpartum thyroiditis.
AB  - Five percent of all pregnant women and 25% of pregnant women with insulin
      dependent diabetes mellitus (IDDM) develop postpartum thyroiditis (PPT) during
      the first year after delivery. PPT has significant morbidity and can be predicted
      prenatally by the presence of thyroid peroxidase (TPO) antibody. Our objective
      was to estimate the cost-effectiveness of screening pregnant women for the TPO
      antibody versus the current strategy of no screening test or an alternative
      strategy of a thyroid-stimulating hormone (TSH) test 6 weeks postpartum. We
      performed cost-effectiveness analysis using a decision tree model that accounted
      for cases of PPT detected, medical outcomes of screening, and costs of screening
      and care. Hypothetical cohorts of 1000 pregnant women with uncomplicated
      pregnancies and 1000 pregnant women with IDDM were used to determine direct
      medical costs, quality-adjusted life years, and cases of PPT detected. The cost
      of testing 1000 pregnant women for TSH at the 6 week postpartum visit was
      $75,000, with an effectiveness of 995.2 quality-adjusted life years resulting in
      a cost-effectiveness ratio of $48,000 per quality-adjusted life year. Checking a
      TPO antibody was more effective (995.5 quality-adjusted life years) but also more
      expensive ($93,000). The incremental cost-effectiveness ratio of the TPO antibody
      strategy was $60,000 per quality-adjusted life year. Results were most sensitive
      to changes in the test characteristics, incidence of disease, and percentage of
      women with PPT who were symptomatic. A separate analysis for women with IDDM
      resulted in an incremental cost-effectiveness ratio of $13,000 per quality
      adjusted life year for the TSH strategy and $32,000 per quality-adjusted life
      year for the TPO strategy. Screening for PPT is likely to be reasonably cost
      effective and should be considered for inclusion as part of routine pregnancy
      care.

PMID- 11571095
TI  - Correlates of surgical treatment type for women with noninvasive and invasive
      breast cancer.
AB  - There is concern that breast-conserving surgery is underused in some breast
      cancer patient subpopulations, including women with ductal carcinoma in situ
      (DCIS), an early-stage form of the disease. We conducted a population-based study
      to identify correlates of surgical treatment type and patient satisfaction,
      comparing women with DCIS and those with invasive disease. We used telephone
      interview and mailed survey of 183 women recently diagnosed with breast cancer
      (oversampling for women with DCIS), identified from the Metropolitan Detroit
      Cancer Surveillance System (response rate 71.2%). Overall, 52.5% of study
      subjects received a mastectomy (48.9%, 45.8%, and 73.5% of women with DCIS, local
      disease, and regional disease, respectively, p < 0.05). One third of women did
      not perceive that they were given a choice between surgical types, and an
      additional one third of women received a surgeon recommendation, most of whom
      received the treatment recommended. Patient attitudes, such as concerns about the
      clinical benefits and risks of specific surgery options, were important
      correlates of treatment choice but did not vary by stage of disease. Knowledge
      about differences in clinical benefits and risks between surgery options was low.
      Finally, satisfaction with the decision-making process was significantly lower in
      women who did not perceive a choice between surgery options. Correlates of breast
      cancer surgery type appeared to be similar for women with DCIS and invasive
      breast cancer, with surgeons playing a dominant role in the process. Results also
      suggested that the decision-making process may be as important for patient
      satisfaction as the treatment chosen.

PMID- 11571096
TI  - Neuropsychological effects of methyltestosterone in women using menopausal
      hormone replacement.
AB  - To observe the effects of androgen replacement on neuropsychological measures in
      menopausal women, healthy menopausal women already using replacement estrogen
      were studied in a randomized, double-blind, active placebo-controlled, crossover
      comparison between two 8-week periods of treatment with (1) 0.625 mg oral
      esterified estrogen (E) alone and (2) in combination with 1.25 mg oral
      methyltestosterone (meT). After an initial baseline session, data were gathered
      at the end of two treatment periods. Scores on standardized psychological tests
      and computerized reaction times were compared between treatments, as was an
      overall outcome score that combined all measures. Added meT significantly
      improved scores on a test of complex information processing, the Switching
      Attention Test, but not on other tests. Mean outcome score showed no net change
      and wide variation. Fourteen subjects had outcome scores >1 SD from the mean, and
      21 had no change. In the estrogen alone condition, three measures predicted
      favorable outcome with added meT: surgically compromised ovarian function, fewer
      physical symptoms, and higher score on a self-image measure of creativity. Added
      meT treatment may improve complex information processing. Despite wide
      disparities in outcome, an increased chance of overall improvement may be
      predicted by specific pretreatment measures.

PMID- 11571097
TI  - The Prevalence of von Willebrand disease in women with abnormal uterine bleeding.
AB  - Although a common symptom of von Willebrand disease is menorrhagia or
      metrorrhagia, the prevalence of this inherited bleeding disorder in women with
      heavy bleeding is not known. This pilot study compared the prevalence rate of von
      Willebrand disease in women with dysfunctional uterine bleeding with the
      prevalence rate in the general population. On average, these women bled for 11.5
      days per month and experienced heavy bleeding for >16 years. Over 60% had been
      treated previously for heavy bleeding. One woman was diagnosed with type 1 von
      Willebrand disease (5% prevalence rate). Larger studies are needed to confirm
      this increased rate of von Willebrand disease in women with abnormal uterine
      bleeding.

PMID- 11571098
TI  - Cumulative duration of breast-feeding influences cortisol levels in
      postmenopausal women.
AB  - Cortisol levels dramatically increase during pregnancy, peak at birth, and
      subsequently decline. However, all previous studies examined women during
      pregnancy and early postpartum. None examined the long-term association of parity
      and lactation with cortisol levels. We examined the relation of reproductive
      history to cortisol levels in postmenopausal women. Subjects were 749 women, aged
      50-89, who were not using estrogen in 1984-1987 when morning cortisol was
      measured. Parity was not significantly associated with cortisol. However, women
      who breast-fed for >12 months had significantly higher cortisol levels than women
      who breast-fed for shorter durations or not at all (p = 0.003). This association
      was stronger among women with three or more births. Duration of breast-feeding is
      a determinant of cortisol levels in postmenopausal women. Because both increased
      cortisol and increased duration of breast-feeding may play protective roles in
      certain autoimmune diseases, such as rheumatoid arthritis, we suggest that the
      beneficial effect of lactation on the course of these diseases may be mediated by
      cortisol.

PMID- 11571099
TI  - Patient gender differences in the diagnosis of depression in primary care.
AB  - Our purpose was to explore why women are more likely than men to be diagnosed as
      depressed by their primary care physician. Women were found to have more
      depressive symptoms as self-reported on the Beck Depression Inventory (BDI).
      Women having high BDI scores (reflecting significant depression) were more likely
      than men with high BDI scores to be diagnosed by their primary care physician (p
      = 0.0295). Female patients made significantly more visits to the clinic than men.
      For both sexes, patients with greater numbers of primary care clinic visits were
      more likely to be diagnosed as depressed. Logistic regression revealed that
      gender has both a direct and indirect (through increased use) effect on the
      likelihood of being diagnosed as depressed. Patient BDI score, clinic use,
      educational level, and marital status were all significantly related to the
      diagnosis of depression. Controlling all other independent variables, women were
      72% more likely than men to be identified as depressed, but this effect did not
      achieve statistical significance (p = 0.0981). In gender-specific analyses, BDI
      and clinic use were again significantly related to the diagnosis of depression
      for both sexes. However, educational and marital status predicted depression
      diagnosis only for women. Separated, divorced, or widowed women were almost five
      times as likely to be diagnosed as depressed as those who were never married, all
      other factors being equal. Clinic use and BDI scores were found to be important
      correlates of the diagnosis of depression. There was some evidence of possible
      gender bias in the diagnosis of depression.

PMID- 11571100
TI  - Sacral insufficiency fractures: a report of two cases and a review of the
      literature.
AB  - Sacral insufficiency fractures (SIF) are a type of stress fracture that occur
      primarily in postmenopausal women. They were first described in 1982 by Lourie
      and have since been frequently overlooked as a cause of low back, buttock, or
      groin pain. We present two cases of SIF to demonstrate the clinical presentation,
      diagnosis, and treatment of patients with SIF. Both patients were elderly women
      with complaints of pelvic and low back pain in the absence of significant trauma.
      Physical examination was significant for marked sacral tenderness. Diagnostic
      imaging supported the diagnosis of SIF. Both patients underwent early
      rehabilitation, including early ambulation, and had good functional outcomes.
      These patients serve to illustrate how conservative treatment yields excellent
      clinical results in the majority of patients, with most reporting improvement
      within 1-2 weeks after fracture and complete resolution of symptoms after 6-12
      months of treatment.

PMID- 11571101
TI  - Influence of pregnancy-related diagnoses on sick-leave data in women aged 16-44.
AB  - Data on sickness absence frequently are used as a measure of morbidity and its
      social consequences in the employed population. The effects of sickness absence,
      as well as any possible differences in diagnoses among pregnant women as compared
      the sick leave data among the total population of women in fertile age have so
      far not been studied. The aim of this study was to investigate the relative
      contribution of pregnant women to the level of sickness absence, in general and
      in different diagnostic groups, as well as the extent to which sick-listed
      pregnant women can be identified through diagnoses on sickness certificates. In a
      cross-sectional study of all sick leave insured women aged 16-44 years (n =
      24,481) in Linkoping, Sweden (117,000 inhabitants), data from two population
      based research registers were used, one of sickness absence for the whole
      population, one of sickness absence among pregnant women in the same population
      and year. Pregnant women (5%) had a significantly higher cumulative incidence of
      sickness absence (0.64) compared with all women (0.18) and accounted for 20% of
      the women listed as absent because of sickness. The duration of the sickness
      absence was also significantly longer among pregnant women, 44.8 days compared
      with 9.7 days among all women. Practically all diagnoses among pregnant women
      were related to pregnancy or back pain (93%). When using diagnoses on the
      sickness certificates, only 46% of all sick-listed pregnant women could be
      identified, suggesting methodological difficulties in studies on sickness
      absence. Studies on sickness absence among women of fertile age should also
      contain information on the proportion of sick-listed pregnant women, as a small
      proportion of pregnant women may have a deep impact on the results and
      conclusions among all women.

PMID- 11571102
TI  - [Functional services of family and community medicine].

PMID- 11571103
TI  - [Being a male or female doctor is different in medical practice].
AB  - OBJECTIVES: To identify the differences between the clinical practice (conduct)
      of male and female doctors and its determining factors; and to find the
      variability in the various conducts studied which is explained by a set of
      variables, gender among them. DESIGN: Cross-sectional, multi-centre descriptive
      study. SETTING: Andalusian health centres with populations of over 100000
      inhabitants. PARTICIPANTS: Selection of 159 primary care doctors with
      postgraduate training by means of simple randomised sampling. 56% were men, 44%
      women, with power of comparisons at 68%. MEASUREMENTS AND MAIN RESULTS: Self
      administered questionnaire to measure the dependent variable, overall conduct
      (clinical practice) and 11 dimensions of this conduct. Independent variables
      were: determinants of conduct identified by the theory of reasoned action
      (attitudes and subjective norm) and by the theory of social learning (self
      efficacy and control locus), gender and other social and demographic variables
      and work conditions variables. Multiple linear regression models were constructed
      to explain each conduct analysed. Being a female doctor affects positively
      overall conduct and conduct in information, psycho-social guidance, prevention of
      obesity, active recruitment for family planning and collaboration with nurses.
      CONCLUSIONS: In Andalusia women general practitioners have a more marked
      orientation towards the psycho-social sides of care than their male colleagues.
      They give more information to their patients and more frequently perform
      preventive activities linked to their gender. They also rely on the work of their
      nurses more than male doctors.

PMID- 11571104
TI  - [Ambulatory mouth surgery. Experience at a buccal-dental health unit in primary
      care].
AB  - OBJECTIVES: To describe the results obtained from conducting non-hospital mouth
      surgery in a buccal-dental health unit, to evaluate the quality of care and to
      monitor its evolution over two years. DESIGN: Descriptive, retrospective study
      with quality assessment methodology. PARTICIPANTS: Oral surgery interventions
      conducted during 1998 and 1999. SETTING: Primary care. Buccal-Dental Health Unit
      at Villanueva de la Serena. MEASUREMENTS AND MAIN RESULTS: 140 interventions took
      place in 1998 and 1999. 12 descriptive variables were analysed. 10 explicit
      standard quality criteria were worked out. Scientific and technical quality was
      measured through compliance rates. The radicular remains (28.6%) and the cordal
      remains included or retained (24.3%) were the most common diagnoses. The most
      frequently employed surgical procedures were: residual root extraction (28.6%)
      and the surgical extraction of included tooth (24.3%). 100% of users had signed
      an informed consent. In 9.9% of procedures a biopsy was performed: it gave 92.8%
      concordance with the diagnosis. In 1998, 6 of the 10 criteria scored above 90%.
      The mean of criteria satisfied per intervention was 7.4. There were clear
      deficiencies in anamnesis data collection (9.24%) and recording of post-operative
      complications (0% compliance). 60% of criteria did not achieve the standard. In
      1999, 40% of criteria had a figure between 99 and 100%. 70% of criteria achieved
      the standard. The quantification of the improvement was significant in anamnesis
      (p < 0.001), analysis (p < 0.001) and post-operative complications (p < 0.001).
      CONCLUSIONS: Performing mouth surgery is a feasible non-hospital service. The
      quality cycle installed was highly effective.

PMID- 11571105
TI  - [Variations in the prevalence and patient profile of white-coat syndrome,
      according to its definition using self-measurement of blood pressure at home].
AB  - OBJECTIVE: To calculate the prevalence of white-coat syndrome (WCS) in patients
      with hypertension, comparing the two most common definitions and their effect on
      the profile of the patient with WCS. DESIGN: Cross-sectional, descriptive
      study.Setting. Urban health centre.Patients. Hypertense patients selected by
      simple randomised sampling from among those included in the hypertension
      programme. MEASUREMENTS: Clinical blood pressure (CBP) from the previous year was
      collected. Home blood pressure (HBP) was measured by the patient with an
      electronic sphygmomanometer. Age, sex, further tests (analysis and
      electrocardiogram) and other clinical features were also recorded. WCS was
      defined as when CBP was above/equal to 140/90 mmHg and HBP was under 135/85 mmHg
      or when the difference between CBP and HBP was more than/equal to 20 mmHg
      systolic and/or 10 mmHg diastolic pressure. RESULTS: In 154 hypertense patients
      (60.4% women) between 38 and 92 years old, mean CBP (141.1/85.3) was higher than
      mean HBP (136.8/79.8). WCS prevalence varied (p = 0.001), depending on the
      definition used (20.1% and 36.4%). The systolic and diastolic mean CBP of the
      last year were higher in those patients with WCS (p < 0.001 for diastolic
      pressure). The profile of hypertense patients with WCS varied according to the
      definition used. CONCLUSIONS: WCS is common in hypertense patients treated in
      Primary Care and may condition an inadequate assessment of the degree of blood
      pressure monitoring. As the way of defining WCS conditions its prevalence, its
      profile and clinical decision-taking, it is essential to agree a uniform
      definition for practical use.

PMID- 11571106
TI  - [Improving care for victims of domestic violence. Impact of a priority
      intervention].
AB  - OBJECTIVE: To evaluate the impact of a priority intervention in the care given to
      women who are victims of domestic violence and their children. DESIGN: Non
      randomised intervention study. SETTING: Urban health centre. PATIENTS: Women and
      children living at a reception centre for families suffering domestic violence
      and who had clinical records opened at the health centre. Pre-intervention group
      (December 1997-July 1999): 36 women, 70 children. Post-intervention group (August
      1999-June 2000): 35 women and 41 children.Interventions. Allocation to a single
      family doctor and paediatrician. Elimination of bureaucratic obstacles and
      prioritised care. Social/family assessment by the social worker. Preferential
      inclusion in programmes: Women: family planning, hepatitis B vaccination,
      pregnancy control, early diagnosis of breast cancer (women > 50), same for
      cervical cancer. Children: child health (< 5) (priority activities: psychomotor
      development and somatometry) and vaccinations. This intervention started in
      August 1999. MEASUREMENTS AND MAIN RESULTS: Measurement of the impact of the
      intervention: bivariant analysis through Chi2 test for qualitative variables and
      Student's t test and U Mann-Whitney test for quantitative variables (alpha 0.05)
      in the pre- and post-intervention groups. Statistically significant differences
      in participation were detected between the pre- and post-intervention groups in
      the following activities: number of visits to programmes (0.49, SD 0.95; 1.01, SD
      1.24, respectively), social and family assessment (83%/100%), family planning
      (14%/51.4%), hepatitis B vaccination (19%/48.7%), early cervical cancer diagnosis
      (0/25.7%), child health (33.4%/70%), vaccinations (26.34%/64%), somametric
      assessment (25%/100%) and psychomotor development assessment (41.6%/94%).
      CONCLUSIONS: Prioritised intervention in families that are victims of domestic
      violence improves their participation in preventive activities.

PMID- 11571107
TI  - [Comparation of reactogenicity of vaccine combinations with an injection volume
      of 0,5 and 1 ml in infants].
AB  - OBJECTIVE: To compare the local and systemic reactogenicity of two vaccine
      associations in infants, in order to ascertain if a greater volume of injection
      is associated with a greater adverse effects rate. DESIGN: Intervention study,
      without random distribution. Site. A unit of vaccinations with free access and
      public dependency. PARTICIPANTS: 228 infants (138 male, 90 female) aged 2, 4 and
      6 months that were attending to compliment their vaccine schedule. INTERVENTIONS:
      To those aged 2 and 6 months (group 1: 108 children) it was administered the
      association DTPw + Hepatitis B + Hib (Tritanrix-HB + Hiberix) with a volume of
      injection of 0,5 ml, and to those aged 4 months (group 2: 120 children) the
      association DTPw + Hib (Anatoxal Diteper + Hibtiter) with a volume of 1 ml. The
      injection was applied in the thigh and paracetamol was indicated in the following
      24 hours. Adverse reactions were registered through telephonic interview, and
      nursing visit of those which might have presented some one. RESULTS: There were
      not meaningful differences between both associations in signs or symptoms
      analyzed (pain, inflammation, aseptic cyst, fever, behavior alterations,
      diarrhea, encephalopathy, hypotonic-hyporesponsive episode or inconsolable
      weeping). With both associations the local reactions rate (0% of inflammation or
      aseptic cyst) and fever (10%) were very inferior to the previous published data.
      CONCLUSION: The vaccine association with a volume of injection of 1 ml did not
      produce more adverse effects than the association of 0,5 ml. Both produced a
      number of local reactions and fever much less than previously published, what is
      attributed to the prophylactic use of paracetamol and other preventive measures.
      Therefore, the association elected for the vaccination at 4 months (DTPw + Hib
      with a volume of 1 ml) is useful and practical to improve vaccine coverage and
      for the welfare of vaccinated infants, upon avoiding them an injection and
      without provoking more adverse reactions.

PMID- 11571108
TI  - [Accidents with biological material in health care workers in 2 primary health
      care areas (1990-1999)].
AB  - OBJECTIVE: To find out the exposures with biological material in health care
      workers in primary health care, registered in the biological accidents database
      from Preventive Medicine Service in Miguel Servet Universitary Hospital of
      Zaragoza. DESIGN: Descriptive study of a retrospective cohort. SITE: Primary
      health care, Areas II and V of Zaragoza.Participants. Workers in this areas,
      distributed by: physician, nursing staff, auxiliary, orderly, housekeeping staff,
      others. MEASUREMENTS AND MAIN RESULTS: Data of: workers, accident, serologic
      source, worker protection and vaccinal status of hepatitis B. The incidence of
      accidents was 26 (period 1997-1999). Most proportion of accidents were declared
      by nursing (78%). The highest occupational incidence was in auxiliary (63 ). In
      90,1% of the cases, the accident was needlestick injury. The source was known in
      67,7% of cases. The accidents occurred in hands in 96,8% of cases, and only one
      third of workers carried gloves. CONCLUSIONS: Results obtained are similar with
      previous studies about this event. We must insist on the need to declare these
      accidents, providing more information and accessibility for the declaration to
      worker. Moreover, we must insist on the correct application in the health care
      field of the standard precautions, because almost 50% of accidents are evitable,
      and to increase hepatitis B vaccination covertures.

PMID- 11571109
TI  - [Alcohol consumption among primary care doctors].
AB  - OBJECTIVE: To find the personal alcohol consumption of primary care (PC) doctors.
      DESIGN: Observational, descriptive and cross-sectional study. SETTING: All the PC
      doctors in our region. PARTICIPANTS: 486 doctors, excluding paediatricians.
      MATERIAL: Closed, anonymous and self-administered survey, divided into two
      sections: a) social and demographic and work variables (7 items); b)
      Questionnaire on personal alcohol consumption (4 questions). MEASUREMENTS AND
      INTERVENTIONS: Descriptive analysis and simple correlations. RESULTS: 227 valid
      surveys were obtained (47.7% participation rate). A) Social and demographic and
      work variables: 67.6% were male, with 63.9% between 36 and 45 years old. 55.3%
      worked in a mixed health centre, 54.4% with tenure. > 40 patients/day (46.6%)
      demanded care. 82.1% were married. Two-child family units predominated (44.4%).
      B) Questionnaire on personal consumption of alcohol: 75.7% of the professionals
      who answered the questionnaire said they were consumers, with "occasionally" the
      most common pattern of consumption (32.33%). In 63.3% the starting age was
      between 16 and 20. Beer was the most common kind of drink. In general,
      consumption predominated in male professionals (78%). However, excess/risk
      consumption was proportionally higher in women (27.7%). CONCLUSIONS: a) Alcohol
      consumption among the doctors surveyed is similar to that found in the general
      population. b) Risk consumption is higher among women doctors.

PMID- 11571111
TI  - [Assessment of a new system of teaching accreditation and reaccreditation of
      health centers].

PMID- 11571110
TI  - [The main health problems according to patients' opinion].
AB  - OBJECTIVE: To know the health problems or diseases that patients of 2 basic
      health areas (BHA) assess as the most important for Spanish population and for
      themselves; to know if any relation exists between these problems and their
      existence in the family or social patients' environment. DESIGN: An observational
      cross-sectional and descriptive study. SETTING: Four clinics of the BHA Sant
      Josep (L'Hospitalet de Llobregat) and 2 clinics of the BHA Sant Marti
      (Barcelones).Patients. The sample consists of 360 patients aged above 26 years
      who attended clinics for some health problem. Participants were chosen by a
      randomised systematic sampling, from May to October 2000. MEASUREMENTS AND MAIN
      RESULTS: Data were gathered from a questionnaire of ten items. According with the
      participants, the main problems for Spanish population and for themselves were:
      cancer, cardiovascular diseases and AIDS. Cancer (58,61%; 95% CI, 53,53-63,69)
      and AIDS (15,27%; 95% CI, 11,56-18,98) are the problems pointed out as research
      priorities. The aparato locomotor (22,10%; 95% CI, 17,82-26,38), hypertension
      (14,74%; 95% CI, 11,08-18,40) and diabetes (13,14%, 95% CI, 9,66-16,62) are the
      main problems suffered by the surveyed. Cancer is the disease that more
      participants' relatives suffered. CONCLUSIONS: Cancer and cardiovascular diseases
      are the pathologies that cause more concern among the surveyed and these are the
      diseases which mostly affect their relatives and relationships. Nevertheless
      their worry for the AIDS don't show their immediate reality. Frequently, patients
      don't recognize the health problem that motivated their visit as a real disease.

PMID- 11571112
TI  - [The legal death certificate].

PMID- 11571113
TI  - [Information in Spanish for patients on the internet].

PMID- 11571114
TI  - [The epidemiology of alarmism: the example of mobile telephone antennas].

PMID- 11571115
TI  - [The revised Texas Grief Inventory adapted to Spanish].

PMID- 11571117
TI  - [Auto-haemotherapy: is it an effective alternative in autoimmune diseases?].

PMID- 11571119
TI  - [Survival outcome in chronic alcoholism: a 10 year follow-up study].
AB  - Alcoholism is a major cause of death. To date, there have been reported few
      studies examining the factors associated with mortality in alcoholics who are
      hospitalized for medical reasons. The aim of this study was to analyze the
      survival rate of those alcoholic subjects and to identify outcome variables.
      PATIENTS AND METHOD: Among all alcoholic patients admitted from January 1986 to
      December 1988 in the Department of Internal Medicine 1 of the Reina Sofia
      University Hospital in Cordoba (Spain), 162 met the inclusion criteria.
      Information was compiled from protocols, medical records,death certificates and
      interviews to patients and family members.A prospective cohort design was also
      used. Average age was 50.7 (10.7) years; 91.4% were males, 69.9% smokers,65.7%
      were married, 19.8% had ascites, and the average follow-up was 8.7 years. 59
      patients survived, 56 died, and 47 did not complete the study period. In the
      covariate analysis, age, marital status,alcoholism duration, bilirubin levels,
      ascites and albumin concentrations had statistical signification. Four variables
      were included in the regression model: age (OR, 1.07; 1.03-1.12); ascites
      (OR,2.09; 1.05-4.15); bilirubin (OR, 1.42; 1.20-1.67) and marital status (OR,
      2.39; 1.17-4.85). CONCLUSIONS: In our study, age, an increase in bilirubin level,
      presence of ascites, and marital status (single, widowed or separated) were
      associated with a significantly lower survival rate in chronic alcoholics.

PMID- 11571120
TI  - [Role of Lactobacillus as protector against vaginal candidiasis].
AB  - BACKGROUND: To evaluate the possible protector role of Lactobacillus against
      vaginal candidiasis. PATIENTS AND METHOD: In vitro studies performed to assess
      the capacity of 15 Lactobacillus strains to block the adhesion of two Candida
      albicans and one C. glabrata strain to vaginal epithelial cells and to inhibit
      the growth of these yeasts. Moreover, the presence of Lactobacillus was analyzed
      in 115 vaginal exudates from women with vaginal candidiasis. RESULTS: Only 8 of
      the 15 lactobacilli studied significantly blocked the adhesion of C. albicans Y18
      to vaginal cells. Lactobacilli from group III showed the greatest blocking
      capacity (62.9%), followed by group II (50.6%) and group I (26.1%). In solid
      assays, none of the 15 Lactobacillus strains studied was able to inhibit growth
      of the 3 yeasts. However, in liquid assays some lactobacilli evidenced a certain
      degree of inhibitory power against C. albicans Y17 (35.7%, 41.7% and 38.1% of
      light transmittance for Lactobacillus groups I, II and III, respectively).
      Lactobacillus was detected in 89.6% of women with vaginal candidiasis (by
      microscopy in 87.8% and by culture in 72.2%). CONCLUSIONS: These results lead us
      to suggest that probably Lactobacillus provides protection against vaginal
      candidiasis.

PMID- 11571121
TI  - [Malnutrition prevalence in institutionalized elderly people in Valencia
      Community, Spain].
AB  - BACKGROUND: The goal of this study was to know the prevalence of malnutrition in
      an institutionalized elderly population according to age and sex. PATIENTS AND
      METHOD: We studied 615 institutionalized patients, with a mean age (SD) of 79.33
      (9.07) years. Anthropometric parameters included weight, height, knee-heel
      length, tricipital and subescapular skin folds, arm perimeter and fat mass.
      Biochemical parameters included: total cholesterol, triglycerides, albumin,
      prealbumin, transferrin,retinol-binding protein, C3 and lymphocyte count.
      Malnutrition prevalence was 26.87% (CI 95%, 23.15-30.86), 29.08% (CI 95%, 22.82
      35.97) in men and 25.59% (CI 95%, 25.01-30.61) in women. Anthropometric
      parameters were found to be decreased in all malnourished patients. Significant
      decreases in albumin and retinol-binding protein concentrations were observed in
      some age groups of malnourished patients. We also found a decrease in the total
      cholesterol level in parallel to an age increase in both sexes, regardless of the
      nutritional status. Triglyceride levels were significantly decreased in both
      males and females with malnutrition. CONCLUSIONS: We detected a high prevalence
      of malnutrition, yet lower than reported in other studies with similar age
      groups.

PMID- 11571122
TI  - [Medical emergencies: more than just a television series].

PMID- 11571123
TI  - [What is an effect modifier?].

PMID- 11571124
TI  - [C-reactive protein as a coronary risk factor].

PMID- 11571125
TI  - [A 20-year-old male with low back pain and osteolytic lesions].

PMID- 11571126
TI  - [Acute orgonophosphate poisoning after fresh fruit intake: an intermediate
      syndrome?].

PMID- 11571127
TI  - [Acute pericarditis as a complication following electric cardioversion].

PMID- 11571128
TI  - [Diarrhea by Clostridium difficile].

PMID- 11571129
TI  - [Acute hepatitis induced by acarbose].

PMID- 11571130
TI  - [Fatal latrodectism in an elderly man].

PMID- 11571131
TI  - [Multiple spontaneous fractures: an exceptional presentation of Cushing's
      syndrome].

PMID- 11571133
TI  - [Renal expression of intercellular adhesion molecule-1 (ICAM-1) in IgA deposit
      mesangial nephropathy. A tubulointerstitial lesion marker].
AB  - BACKGROUND: The aim of this study was to determine the significance of the renal
      expression of ICAM-1 in IgA nephropathy (IgAN). PATIENTS AND METHOD: First, we
      identified ICAM-1 (CD54) expression in tubular epithelial cells and interstitial
      leucocytes in renal biopsies from 45 patients with IgAN and 29 patients with non
      glomerulonephritis nephropathy (non-GN). We then analysed the relationship
      between this expression and both histological and clinical data at the time of
      renal biopsy and after 2.4 (2) (X [SD]) years in IgAN, and 1.8 (1.5) years in non
      GN. RESULTS: In IgAN, tubular ICAM-1 positive staining was seen in 25 (55%)
      biopsies; it was associated with extracapillary proliferation, glomerulosclerosis
      involving less than 50% of glomerular area, interstitial cell infiltration and
      tubular atrophy. ICAM-1 positive interstitial leucocytes were 234 (307)/mm2; this
      expression correlated with glomerulosclerosis, tubular atrophy, interstitial
      fibrosis and serum creatinine (Cr) level. In patients with 50% increase in Cr
      level, ICAM-1 positive interstitial leucocytes were 516 (360)/mm2 as compared
      with 66 (87.8)/mm2 (U = 16; p < 0.005) in patients with stable Cr. In non-GN,
      tubular ICAM-1 expression was observed in 7 (24%) biopsies. CONCLUSIONS: Tubular
      and Interstitial expression of ICAM-1 can be a marker of tubulointerstitial
      damage in IgAN. Interstitial ICAM-1, rather than tubular ICAM-1, may predict the
      progression of this disease.

PMID- 11571134
TI  - ?

PMID- 11571135
TI  - Counting the uncountable: statistical approaches to estimating microbial
      diversity.

PMID- 11571136
TI  - Growth of the bacteriocin-producing Lactobacillus sakei strain CTC 494 in MRS
      broth is strongly reduced due to nutrient exhaustion: a nutrient depletion model
      for the growth of lactic acid bacteria.
AB  - Although commercial MRS broth has been designed to allow excellent growth of
      lactobacilli, most of these bacteria are still subjected to a self-inhibiting
      process. The most likely explanation is the accumulation of lactic acid or other
      toxic end products and the depletion of nutrients. In this study, the self
      inhibition of Lactobacillus sakei CTC 494 was analyzed in a kinetic way, and a
      nutrient depletion model was set up to describe the growth inhibition process.
      This simple model has considerable advantages compared to commonly used
      descriptive models such as the logistic growth equation. It offers a better fit
      and a more realistic description of the growth data by taking into account both
      growth inhibition due to lactic acid production and changes in growth rates due
      to nutrient depletion. Depending on the fermentation conditions, in MRS broth
      there appears to be a strong decrease of the specific growth rate over time. Some
      undefined compounds present in the complex nitrogen source of MRS broth appear to
      be of crucial importance because of their limited availability. Moreover,
      nutrient availability affects bacteriocin production through its effect on cell
      growth as well as on the bacteriocin production per cell. A plateau value for the
      bacteriocin production by L. sakei CTC 494 was observed.

PMID- 11571137
TI  - Changes in populations of rhizosphere bacteria associated with take-all disease
      of wheat.
AB  - Take-all, caused by Gaeumannomyces graminis var. tritici, is one of the most
      important fungal diseases of wheat worldwide. Knowing that microbe-based
      suppression of the disease occurs in monoculture wheat fields following severe
      outbreaks of take-all, we analyzed the changes in rhizosphere bacterial
      communities following infection by the take-all pathogen. Several bacterial
      populations were more abundant on diseased plants than on healthy plants, as
      indicated by higher counts on a Pseudomonas-selective medium and a higher
      fluorescence signal in terminal restriction fragment length polymorphism analyses
      of amplified 16S ribosomal DNA (rDNA). Amplified rDNA restriction analysis
      (ARDRA) of the most abundant cultured populations showed a shift in dominance
      from Pseudomonas to Chryseobacterium species in the rhizosphere of diseased
      plants. Fluorescence-tagged ARDRA of uncultured rhizosphere washes revealed an
      increase in ribotypes corresponding to several bacterial genera, including those
      subsequently identified by partial 16S sequencing as belonging to species of
      alpha-, beta-, and gamma-proteobacteria, sphingobacteria, and flavobacteria. The
      functional significance of some of these populations was investigated in vitro.
      Of those isolated, only a small subset of the most abundant Pseudomonas spp. and
      a phlD(+) Pseudomonas sp. showed any significant ability to inhibit G. graminis
      var. tritici directly. When cultured strains were mixed with the inhibitory
      phlD(+) Pseudomonas strain, the Chryseobacterium isolates showed the least
      capacity to inhibit this antagonist of the pathogen, indicating that increases in
      Chryseobacterium populations may facilitate the suppression of take-all by 2,4
      diacetylphloroglucinol-producing phlD(+) pseudomonads.

PMID- 11571138
TI  - EndB, a multidomain family 44 cellulase from Ruminococcus flavefaciens 17, binds
      to cellulose via a novel cellulose-binding module and to another R. flavefaciens
      protein via a dockerin domain.
AB  - The mechanisms by which cellulolytic enzymes and enzyme complexes in Ruminococcus
      spp. bind to cellulose are not fully understood. The product of the newly
      isolated cellulase gene endB from Ruminococcus flavefaciens 17 was purified as a
      His-tagged product after expression in Escherichia coli and found to be able to
      bind directly to crystalline cellulose. The ability to bind cellulose is shown to
      be associated with a novel cellulose-binding module (CBM) located within a region
      of 200 amino acids that is unrelated to known protein sequences. EndB (808 amino
      acids) also contains a catalytic domain belonging to glycoside hydrolase family
      44 and a C-terminal dockerin-like domain. Purified EndB is also shown to bind
      specifically via its dockerin domain to a polypeptide of ca. 130 kDa present
      among supernatant proteins from Avicel-grown R. flavefaciens that attach to
      cellulose. The protein to which EndB attaches is a strong candidate for the
      scaffolding component of a cellulosome-like multienzyme complex recently
      identified in this species (S.-Y. Ding et al., J. Bacteriol. 183:1945-1953,
      2001). It is concluded that binding of EndB to cellulose may occur both through
      its own CBM and potentially also through its involvement in a cellulosome
      complex.

PMID- 11571139
TI  - Fluorescent acid-fast microscopy for measuring phagocytosis of Mycobacterium
      avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum by
      Tetrahymena pyriformis and their intracellular growth.
AB  - Fluorescent acid-fast microscopy (FAM) was used to enumerate intracellular
      Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium scrofulaceum
      in the ciliated phagocytic protozoan Tetrahymena pyriformis. There was a linear
      relationship between FAM and colony counts of M. avium cells both from cultures
      and within protozoa. The Ziehl-Neelsen acid-fast stain could not be used to
      enumerate intracellular mycobacteria because uninfected protozoa contained acid
      fast, bacterium-like particles. Starved, 7-day-old cultures of T. pyriformis
      transferred into fresh medium readily phagocytized M. avium, M. intracellulare,
      and M. scrofulaceum. Phagocytosis was rapid and reached a maximum in 30 min. M.
      avium, M. intracellulare, and M. scrofulaceum grew within T. pyriformis,
      increasing by factors of 4- to 40-fold after 5 days at 30 degrees C.
      Intracellular M. avium numbers remained constant over a 25-day period of growth
      (by transfer) of T. pyriformis. Intracellular M. avium cells also survived
      protozoan encystment and germination. The growth and viability of T. pyriformis
      were not affected by mycobacterial infection. The results suggest that free
      living phagocytic protozoa may be natural hosts and reservoirs for M. avium, M.
      intracellulare, and M. scrofulaceum.

PMID- 11571140
TI  - Effect of selenite on growth and protein synthesis in the phototrophic bacterium
      Rhodobacter sphaeroides.
AB  - The effect of selenite on the growth rate and protein synthesis has been
      investigated in Rhodobacter sphaeroides. This photosynthetic bacterium
      efficiently reduces selenite with intracellular accumulation under both dark
      aerobic and anaerobic photosynthetic conditions. Addition of 1 mM selenite under
      these two growth conditions does not affect the final cell density, although a
      marked slowdown in growth rate is observed under aerobic growth. The proteome
      analysis of selenite response by two-dimensional gel electrophoresis shows an
      enhanced synthesis of some chaperones, an elongation factor, and enzymes
      associated to oxidative stress. The induction of these antioxidant proteins
      confirms that the major toxic effect of selenite is the formation of reactive
      oxygen species during its metabolism. In addition, we show that one mutant unable
      to precipitate selenite, selected from a transposon library, is affected in the
      smoK gene. This encodes a constituent of a putative ABC transporter implicated in
      the uptake of polyols. This mutant is less sensitive to selenite and does not
      express stress proteins identified in the wild type in response to selenite. This
      suggests that the entry of selenite into the cytoplasm is mediated by a polyol
      transporter in R. sphaeroides.

PMID- 11571141
TI  - Growth of Pseudomonas mendocina on Fe(III) (hydr)oxides.
AB  - Although iron (Fe) is an essential element for almost all living organisms,
      little is known regarding its acquisition from the insoluble Fe(III) (hydr)oxides
      in aerobic environments. In this study a strict aerobe, Pseudomonas mendocina,
      was grown in batch culture with hematite, goethite, or ferrihydrite as a source
      of Fe. P. mendocina obtained Fe from these minerals in the following order:
      goethite > hematite > ferrihydrite. Furthermore, Fe release from each of the
      minerals appears to have occurred in excess, as evidenced by the growth of P.
      mendocina in the medium above that of the insoluble Fe(III) (hydr)oxide
      aggregates, and this release was independent of the mineral's surface area. These
      results demonstrate that an aerobic microorganism was able to obtain Fe for
      growth from several insoluble Fe minerals and did so with various growth rates.

PMID- 11571142
TI  - Role of sigma(B) in heat, ethanol, acid, and oxidative stress resistance and
      during carbon starvation in Listeria monocytogenes.
AB  - To determine the contribution of sigma B (sigma(B)) to survival of stationary
      phase Listeria monocytogenes cells following exposure to environmental stresses,
      we compared the viability of strain 10403S with that of an isogenic nonpolar sigB
      null mutant strain after exposure to heat (50 degrees C), ethanol (16.5%), or
      acid (pH 2.5). Strain viabilities were also determined under the same conditions
      in cultures that had been previously exposed to sublethal levels of the same
      stresses (45 degrees C, 5% ethanol, or pH 4.5). The DeltasigB and wild-type
      strains had similar viabilities following exposure to ethanol and heat, but the
      DeltasigB strain was almost 10,000-fold more susceptible to lethal acid stress
      than its parent strain. However, a 1-h preexposure to pH 4.5 yielded a 1,000-fold
      improvement in viability for the DeltasigB strain. These results suggest the
      existence in L. monocytogenes of both a sigma(B)-dependent mechanism and a pH
      dependent mechanism for acid resistance in the stationary phase. sigma(B)
      contributed to resistance to both oxidative stress and carbon starvation in L.
      monocytogenes. The DeltasigB strain was 100-fold more sensitive to 13.8 mM cumene
      hydroperoxide than the wild-type strain. Following glucose depletion, the
      DeltasigB strain lost viability more rapidly than the parent strain. sigma(B)
      contributions to viability during carbon starvation and to acid resistance and
      oxidative stress resistance support the hypothesis that sigma(B) plays a role in
      protecting L. monocytogenes against environmental adversities.

PMID- 11571143
TI  - beta-Glutamate as a substrate for glutamine synthetase.
AB  - The conversion of beta-glutamate to beta-glutamine by archaeal and bacterial
      glutamine synthetase (GS) enzymes has been examined. The GS from
      Methanohalophilus portucalensis (which was partially purified) is capable of
      catalyzing the amidation of this substrate with a rate sevenfold less than the
      rate obtained with alpha-glutamate. Recombinant GS from the archaea Methanococcus
      jannaschii and Archaeoglobus fulgidus were considerably more selective for alpha
      glutamate than beta-glutamate as a substrate. All the archaeal enzymes were much
      less selective than the two bacterial GS (from Escherichia coli and Bacillus
      subtilis), whose specific activities towards beta-glutamate were much smaller
      than rates with the alpha-isomer. These results are discussed in light of the
      observation that beta-glutamate is accumulated as an osmolyte in many archaea
      while beta-glutamine (produced by glutamine synthetase) is used as an osmolyte
      only in M. portucalensis.

PMID- 11571144
TI  - Insertion or deletion of the Cheo box modifies radiation inducibility of
      Clostridium promoters.
AB  - Radiation-inducible promoters are being used in many viral vector systems to
      obtain spatial and temporal control of gene expression. It was previously proven
      that radiation-induced gene expression can also be obtained in a bacterial vector
      system using anaerobic apathogenic clostridia. The effect of radiation
      inducibility was detected using mouse tumor necrosis factor alpha (mTNF-alpha) as
      a model protein under regulation of the radiation-inducible recA promoter. In
      this report, experiments are described in which this recA promoter was modified
      in order to increase radiation responsiveness. Incorporation of an extra Cheo box
      in the recA promoter region resulted in an increase in mTNF-alpha secretion from
      44% for the wild-type promoter to 412% for the promoter with an extra Cheo box
      after a single irradiation dose of 2 Gy. Deletion of the Cheo box in the promoter
      region eliminated radiation inducibility. These results prove that the Cheo box
      in the recA promoter is indeed the radiation-responsive element. We also tested
      whether we could induce the constitutive endo-beta-1,4-glucanase promoter (eglA)
      via ionizing irradiation by introducing a Cheo box in the promoter region. While
      the use of the constitutive promoter did not lead to an increase in mTNF-alpha
      secretion after irradiation, the introduction of a Cheo box resulted in a 242%
      increase in mTNF-alpha secretion. Reverse transcriptase PCR of RNA samples
      isolated from irradiated and nonirradiated bacterial cultures demonstrated that
      the increase in secretion was the result of enhanced transcription of the mTNF
      alpha gene.

PMID- 11571145
TI  - Anaerobic mineralization of toluene by enriched sediments with quinones and humus
      as terminal electron acceptors.
AB  - The anaerobic microbial oxidation of toluene to CO(2) coupled to humus
      respiration was demonstrated by use of enriched anaerobic sediments from the
      Amsterdam petroleum harbor (APH) and the Rhine River. Both highly purified soil
      humic acids (HPSHA) and the humic quinone moiety model compound anthraquinone-2,6
      disulfonate (AQDS) were utilized as terminal electron acceptors. After 2 weeks of
      incubation, 50 and 85% of added uniformly labeled [(13)C]toluene were recovered
      as (13)CO(2) in HPSHA- and AQDS-supplemented APH sediment enrichment cultures,
      respectively; negligible recovery occurred in unsupplemented cultures. The
      conversion of [(13)C]toluene agreed with the high level of recovery of electrons
      as reduced humus or as anthrahydroquinone-2,6-disulfonate. APH sediment was also
      able to use nitrate and amorphous manganese dioxide as terminal electron
      acceptors to support the anaerobic biodegradation of toluene. The addition of
      substoichiometric amounts of humic acids to bioassay reaction mixtures containing
      amorphous ferric oxyhydroxide as a terminal electron acceptor led to more than
      65% conversion of toluene (1 mM) after 11 weeks of incubation, a result which
      paralleled the partial recovery of electron equivalents as acid-extractable
      Fe(II). Negligible conversion of toluene and reduction of Fe(III) occurred in
      these bioassay reaction mixtures when humic acids were omitted. The present study
      provides clear quantitative evidence for the mineralization of an aromatic
      hydrocarbon by humus-respiring microorganisms. The results indicate that humic
      substances may significantly contribute to the intrinsic bioremediation of
      anaerobic sites contaminated with priority pollutants by serving as terminal
      electron acceptors.

PMID- 11571146
TI  - Characterization of bacterial and fungal soil communities by automated ribosomal
      intergenic spacer analysis fingerprints: biological and methodological
      variability.
AB  - Automated rRNA intergenic spacer analysis (ARISA) was used to characterise
      bacterial (B-ARISA) and fungal (F-ARISA) communities from different soil types.
      The 16S-23S intergenic spacer region from the bacterial rRNA operon was amplified
      from total soil community DNA for B-ARISA. Similarly, the two internal
      transcribed spacers and the 5.8S rRNA gene (ITS1-5.8S-ITS2) from the fungal rRNA
      operon were amplified from total soil community DNA for F-ARISA. Universal
      fluorescence-labeled primers were used for the PCRs, and fragments of between 200
      and 1,200 bp were resolved on denaturing polyacrylamide gels by use of an
      automated sequencer with laser detection. Methodological (DNA extraction and PCR
      amplification) and biological (inter- and intrasite) variations were evaluated by
      comparing the number and intensity of peaks (bands) between electrophoregrams
      (profiles) and by multivariate analysis. Our results showed that ARISA is a high
      resolution, highly reproducible technique and is a robust method for
      discriminating between microbial communities. To evaluate the potential biases in
      community description provided by ARISA, we also examined databases on length
      distribution of ribosomal intergenic spacers among bacteria (L. Ranjard, E.
      Brothier, and S. Nazaret, Appl. Environ. Microbiol. 66:5334-5339, 2000) and
      fungi.

PMID- 11571147
TI  - Differential effects of pH on the pore-forming properties of Bacillus
      thuringiensis insecticidal crystal toxins.
AB  - The effect of pH on the pore-forming ability of two Bacillus thuringiensis
      toxins, Cry1Ac and Cry1C, was examined with midgut brush border membrane vesicles
      isolated from the tobacco hornworm, Manduca sexta, and a light-scattering assay.
      In the presence of Cry1Ac, membrane permeability remained high over the entire pH
      range tested (6.5 to 10.5) for KCl and tetramethylammonium chloride, but was much
      lower at pH 6.5 than at higher pHs for potassium gluconate, sucrose, and
      raffinose. On the other hand, the Cry1C-induced permeability to all substrates
      tested was much higher at pH 6.5, 7.5, and 8.5 than at pH 9.5 and 10.5. These
      results indicate that the pores formed by Cry1Ac are significantly smaller at pH
      6.5 than under alkaline conditions, whereas the pore-forming ability of Cry1C
      decreases sharply above pH 8.5. The reduced activity of Cry1C at high pH
      correlates well with the fact that its toxicity for M. sexta is considerably
      weaker than that of Cry1Aa, Cry1Ab, and Cry1Ac. However, Cry1E, despite having a
      toxicity comparable to that of Cry1C, formed channels as efficiently as the Cry1A
      toxins at pH 10.5. These results strongly suggest that although pH can influence
      toxin activity, additional factors also modulate toxin potency in the insect
      midgut.

PMID- 11571148
TI  - Simultaneous recovery of RNA and DNA from soils and sediments.
AB  - Recovery of mRNA from environmental samples for measurement of in situ metabolic
      activities is a significant challenge. A robust, simple, rapid, and effective
      method was developed for simultaneous recovery of both RNA and DNA from soils of
      diverse composition by adapting our previous grinding-based cell lysis method
      (Zhou et al., Appl. Environ. Microbiol. 62:316-322, 1996) for DNA extraction. One
      of the key differences is that the samples are ground in a denaturing solution at
      a temperature below 0 degrees C to inactivate nuclease activity. Two different
      methods were evaluated for separating RNA from DNA. Among the methods examined
      for RNA purification, anion exchange resin gave the best results in terms of RNA
      integrity, yield, and purity. With the optimized protocol, intact RNA and high
      molecular-weight DNA were simultaneously recovered from 19 soil and stream
      sediment samples of diverse composition. The RNA yield from these samples ranged
      from 1.4 to 56 microg g of soil(-1) dry weight), whereas the DNA yield ranged
      from 23 to 435 microg g(-1). In addition, studies with the same soil sample
      showed that the DNA yield was, on average, 40% higher than that in our previous
      procedure and 68% higher than that in a commercial bead milling method. For the
      majority of the samples, the DNA and RNA recovered were of sufficient purity for
      nuclease digestion, microarray hybridization, and PCR or reverse transcription
      PCR amplification.

PMID- 11571149
TI  - Characterization of a highly thermostable alkaline phosphatase from the
      euryarchaeon Pyrococcus abyssi.
AB  - This work reports the first isolation and characterization of an alkaline
      phosphatase (AP) from a hyperthermophilic archaeon. An AP gene from Pyrococcus
      abyssi, a euryarchaeon isolated from a deep-sea hydrothermal vent, was cloned and
      the enzyme expressed in Escherichia coli. Analysis of the sequence showed
      conservation of the active site and structural elements of the E. coli AP. The
      recombinant AP was purified and characterized. Monomeric and homodimeric active
      forms were detected, with a monomer molecular mass of 54 kDa. Apparent optimum pH
      and temperature were estimated at 11.0 and 70 degrees C, respectively. Thus far,
      P. abyssi AP has been demonstrated to be the most thermostable AP, with half
      lives at 100 and 105 degrees C of 18 and 5 h, respectively. Enzyme activity was
      found to be dependent on divalent cations: metal ion chelators inhibited
      activity, whereas the addition of exogenous Mg(II), Zn(II), and Co(II) increased
      activity. The enzyme was inhibited by inorganic phosphate, but not by molybdate
      and vanadate. Strong inhibitory effects were observed in the presence of thiol
      reducing agents, although cysteine residues of the P. abyssi AP were not found to
      be incorporated within intra- or interchain disulfide bonds. In addition, P.
      abyssi AP was demonstrated to dephosphorylate linear DNA fragments with
      dephosphorylation efficiencies of 93.8 and 84.1% with regard to cohesive and
      blunt ends, respectively.

PMID- 11571150
TI  - Extracellular heme peroxidases in actinomycetes: a case of mistaken identity.
AB  - Actinomycetes secrete into their surroundings a suite of enzymes involved in the
      biodegradation of plant lignocellulose; these have been reported to include both
      hydrolytic and oxidative enzymes, including peroxidases. Reports of secreted
      peroxidases have been based upon observations of peroxidase-like activity
      associated with fractions that exhibit optical spectra reminiscent of heme
      peroxidases, such as the lignin peroxidases of wood-rotting fungi. Here we show
      that the appearance of the secreted pseudoperoxidase of the thermophilic
      actinomycete Thermomonospora fusca BD25 is also associated with the appearance of
      a heme-like spectrum. The species responsible for this spectrum is a
      metalloporphyrin; however, we show that this metalloporphyrin is not heme but
      zinc coproporphyrin. The same porphyrin was found in the growth medium of the
      actinomycete Streptomyces viridosporus T7A. We therefore propose that earlier
      reports of heme peroxidases secreted by actinomycetes were due to the incorrect
      assignment of optical spectra to heme groups rather than to non-iron-containing
      porphyrins and that lignin-degrading heme peroxidases are not secreted by
      actinomycetes. The porphyrin, an excretory product, is degraded during peroxidase
      assays. The low levels of secreted peroxidase activity are associated with a
      nonheme protein fraction previously shown to contain copper. We suggest that the
      role of the secreted copper-containing protein may be to bind and detoxify metals
      that can cause inhibition of heme biosynthesis and thus stimulate porphyrin
      excretion.

PMID- 11571151
TI  - Identification of bacteria in pasteurized zucchini purees stored at different
      temperatures and comparison with those found in other pasteurized vegetable
      purees.
AB  - One hundred nineteen isolates from a commercial zucchini puree stored at 4, 10,
      and 20 to 25 degrees C were fingerprinted using repetitive sequence-based PCR
      (REP-PCR) and classified into 35 REP types. One representative isolate of each
      REP type was subsequently identified by API50CHB/20E profile and partial rrs gene
      sequence analysis. Nine REP types were misidentified by the API system. Strains
      were misidentified as being in the Bacillus circulans (group 2) API taxon or in
      taxa with a low number of positive API characters such as Brevibacillus brevis. A
      phylogenetic analysis pointed to one new species of Bacillus and three new
      species of Paenibacillus among the misidentified REP types. Bacterial components
      in zucchini puree were compared phenotypically with those obtained in previous
      work on broccoli, carrot, leek, potato, and split pea purees, based on simple
      matching coefficient and unweighted pair group method with averages cluster
      analysis. Out of 254 strains, 69 strains previously identified as B. circulans
      (group 2) or B. circulans/B. macerans/B. polymyxa were assigned to a new
      Paenibacillus taxon phylogenetically related to P. azotofixans. Storage
      conditions at 4 degrees C favored the development of "B. macroides/B. maroccanus"
      and Paenibacillus spp. in zucchini purees and Paenibacillus spp. in other purees.
      Storage conditions at 20 to 25 degrees C favored the development of B. subtilis
      group (B. licheniformis and B. subtilis) and B. cereus group strains. At 10
      degrees C, Paenibacillus spp. were always present at high frequencies, whereas
      the occurrence of B. macroides/B. maroccanus (in zucchini purees), B. cereus, and
      B. pumilus varied with the experiment.

PMID- 11571152
TI  - Evidence for the biosynthesis of bryostatins by the bacterial symbiont
      "Candidatus Endobugula sertula" of the bryozoan Bugula neritina.
AB  - The marine bryozoan, Bugula neritina, is the source of the bryostatins, a family
      of macrocyclic lactones with anticancer activity. Bryostatins have long been
      suspected to be bacterial products. B. neritina harbors the uncultivated gamma
      proteobacterial symbiont "Candidatus Endobugula sertula." In this work several
      lines of evidence are presented that show that the symbiont is the most likely
      source of bryostatins. Bryostatins are complex polyketides similar to bacterial
      secondary metabolites synthesized by modular type I polyketide synthases (PKS-I).
      PKS-I gene fragments were cloned from DNA extracted from the B. neritina-"E.
      sertula" association, and then primers specific to one of these clones, KSa, were
      shown to amplify the KSa gene specifically and universally from total B. neritina
      DNA. In addition, a KSa RNA probe was shown to bind specifically to the symbiotic
      bacteria located in the pallial sinus of the larvae of B. neritina and not to B.
      neritina cells or to other bacteria. Finally, B. neritina colonies grown in the
      laboratory were treated with antibiotics to reduce the numbers of bacterial
      symbionts. Decreased symbiont levels resulted in the reduction of the KSa signal
      as well as the bryostatin content. These data provide evidence that the symbiont
      E. sertula has the genetic potential to make bryostatins and is necessary in full
      complement for the host bryozoan to produce normal levels of bryostatins. This
      study demonstrates that it may be possible to clone bryostatin genes from B.
      neritina directly and use these to produce bryostatins in heterologous host
      bacteria.

PMID- 11571153
TI  - The enterococcal surface protein, Esp, is involved in Enterococcus faecalis
      biofilm formation.
AB  - The enterococcal surface protein, Esp, is a high-molecular-weight surface protein
      of unknown function whose frequency is significantly increased among infection
      derived Enterococcus faecalis isolates. In this work, a global structural
      similarity was found between Bap, a biofilm-associated protein of Staphylococcus
      aureus, and Esp. Analysis of the relationship between the presence of the Esp
      encoding gene (esp) and the biofilm formation capacity in E. faecalis
      demonstrated that the presence of the esp gene is highly associated (P < 0.0001)
      with the capacity of E. faecalis to form a biofilm on a polystyrene surface,
      since 93.5% of the E. faecalis esp-positive isolates were capable of forming a
      biofilm. Moreover, none of the E. faecalis esp-deficient isolates were biofilm
      producers. Depending on the E. faecalis isolate, insertional mutagenesis of esp
      caused either a complete loss of the biofilm formation phenotype or no apparent
      phenotypic defect. Complementation studies revealed that Esp expression in an E.
      faecalis esp-deficient strain promoted primary attachment and biofilm formation
      on polystyrene and polyvinyl chloride plastic from urine collection bags.
      Together, these results demonstrate that (i) biofilm formation capacity is
      widespread among clinical E. faecalis isolates, (ii) the biofilm formation
      capacity is restricted to the E. faecalis strains harboring esp, and (iii) Esp
      promotes primary attachment and biofilm formation of E. faecalis on abiotic
      surfaces.

PMID- 11571154
TI  - Physiological role of beta-phosphoglucomutase in Lactococcus lactis.
AB  - A beta-phosphoglucomutase (beta-PGM) mutant of Lactococcus lactis subsp. lactis
      ATCC 19435 was constructed using a minimal integration vector and double
      crossover recombination. The mutant and the wild-type strain were grown under
      controlled conditions with different sugars to elucidate the role of beta-PGM in
      carbohydrate catabolism and anabolism. The mutation did not significantly affect
      growth, product formation, or cell composition when glucose or lactose was used
      as the carbon source. With maltose or trehalose as the carbon source the wild
      type strain had a maximum specific growth rate of 0.5 h(-1), while the deletion
      of beta-PGM resulted in a maximum specific growth rate of 0.05 h(-1) on maltose
      and no growth at all on trehalose. Growth of the mutant strain on maltose
      resulted in smaller amounts of lactate but more formate, acetate, and ethanol,
      and approximately 1/10 of the maltose was found as beta-glucose 1-phosphate in
      the medium. Furthermore, the beta-PGM mutant cells grown on maltose were
      considerably larger and accumulated polysaccharides which consisted of alpha-1,4
      bound glucose units. When the cells were grown at a low dilution rate in a
      glucose and maltose mixture, the wild-type strain exhibited a higher carbohydrate
      content than when grown at higher growth rates, but still this content was lower
      than that in the beta-PGM mutant. In addition, significant differences in the
      initial metabolism of maltose and trehalose were found, and cell extracts did not
      digest free trehalose but only trehalose 6-phosphate, which yielded beta-glucose
      1-phosphate and glucose 6-phosphate. This demonstrates the presence of a novel
      enzymatic pathway for trehalose different from that of maltose metabolism in L.
      lactis.

PMID- 11571155
TI  - Numerical analysis of grassland bacterial community structure under different
      land management regimens by using 16S ribosomal DNA sequence data and denaturing
      gradient gel electrophoresis banding patterns.
AB  - Bacterial diversity in unimproved and improved grassland soils was assessed by
      PCR amplification of bacterial 16S ribosomal DNA (rDNA) from directly extracted
      soil DNA, followed by sequencing of ~45 16S rDNA clones from each of three
      unimproved and three improved grassland samples (A. E. McCaig, L. A. Glover, and
      J. I. Prosser, Appl. Environ. Microbiol. 65:1721-1730, 1999) or by denaturing
      gradient gel electrophoresis (DGGE) of total amplification products. Semi
      improved grassland soils were analyzed only by DGGE. No differences between
      communities were detected by calculation of diversity indices and similarity
      coefficients for clone data (possibly due to poor coverage). Differences were not
      observed between the diversities of individual unimproved and improved grassland
      DGGE profiles, although considerable spatial variation was observed among
      triplicate samples. Semi-improved grassland samples, however, were less diverse
      than the other grassland samples and had much lower within-group variation. DGGE
      banding profiles obtained from triplicate samples pooled prior to analysis
      indicated that there was less evenness in improved soils, suggesting that
      selection for specific bacterial groups occurred. Analysis of DGGE profiles by
      canonical variate analysis but not by principal-coordinate analysis, using
      unweighted data (considering only the presence and absence of bands) and weighted
      data (considering the relative intensity of each band), demonstrated that there
      were clear differences between grasslands, and the results were not affected by
      weighting of data. This study demonstrated that quantitative analysis of data
      obtained by community profiling methods, such as DGGE, can reveal differences
      between complex microbial communities.

PMID- 11571156
TI  - Mutations in the listerial proB gene leading to proline overproduction: effects
      on salt tolerance and murine infection.
AB  - The observed sensitivity of Listeria monocytogenes to the toxic proline analogue
      L-azetidine-2-carboxylic acid (AZ) suggested that proline synthesis in Listeria
      may be regulated by feedback inhibition of gamma-glutamyl kinase (GK), the first
      enzyme of the proline biosynthesis pathway, encoded by the proB gene. Taking
      advantage of the Epicurian coli mutator strain XL1-Red, we performed random
      mutagenesis of the recently described proBA operon and generated three
      independent mutations in the listerial proB homologue, leading to proline
      overproduction and salt tolerance when expressed in an E. coli (DeltaproBA)
      background. While each of the mutations (located within a conserved 26-amino-acid
      region of GK) was shown to confer AZ resistance (AZ(r)) on an L. monocytogenes
      proBA mutant, listerial transformants failed to exhibit the salt-tolerant
      phenotype observed in E. coli. Since proline accumulation has previously been
      linked to the virulence potential of a number of pathogenic bacteria, we analyzed
      the effect of proline overproduction on Listeria pathogenesis. However, our
      results suggest that as previously described for proline auxotrophy, proline
      hyperproduction has no apparent impact on the virulence potential of Listeria.

PMID- 11571157
TI  - Growth and phylogenetic properties of novel bacteria belonging to the epsilon
      subdivision of the Proteobacteria enriched from Alvinella pompejana and deep-sea
      hydrothermal vents.
AB  - Recent molecular characterizations of microbial communities from deep-sea
      hydrothermal sites indicate the predominance of bacteria belonging to the epsilon
      subdivision of Proteobacteria (epsilon Proteobacteria). Here, we report the first
      enrichments and characterizations of four epsilon Proteobacteria that are
      directly associated with Alvinella pompejana, a deep sea hydrothermal vent
      polychete, or with hydrothermal vent chimney samples. These novel bacteria were
      moderately thermophilic sulfur-reducing heterotrophs growing on formate as the
      energy and carbon source. In addition, two of them (Am-H and Ex-18.2) could grow
      on sulfur lithoautrotrophically using hydrogen as the electron donor. Optimal
      growth temperatures of the bacteria ranged from 41 to 45 degrees C. Phylogenetic
      analysis of the small-subunit ribosomal gene of the two heterotrophic bacteria
      demonstrated 95% similarity to Sulfurospirillum arcachonense, an epsilon
      Proteobacteria isolated from an oxidized marine surface sediment. The autotrophic
      bacteria grouped within a deeply branching clade of the epsilon Proteobacteria,
      to date composed only of uncultured bacteria detected in a sample from a
      hydrothermal vent along the mid-Atlantic ridge. A molecular survey of various
      hydrothermal vent environments demonstrated the presence of two of these bacteria
      (Am-N and Am-H) in more than one geographic location and habitat. These results
      suggest that certain epsilon Proteobacteria likely fill important niches in the
      environmental habitats of deep-sea hydrothermal vents, where they contribute to
      overall carbon and sulfur cycling at moderate thermophilic temperatures.

PMID- 11571158
TI  - A large gene cluster encoding several magnetosome proteins is conserved in
      different species of magnetotactic bacteria.
AB  - In magnetotactic bacteria, a number of specific proteins are associated with the
      magnetosome membrane (MM) and may have a crucial role in magnetite
      biomineralization. We have cloned and sequenced the genes of several of these
      polypeptides in the magnetotactic bacterium Magnetospirillum gryphiswaldense that
      could be assigned to two different genomic regions. Except for mamA, none of
      these genes have been previously reported to be related to magnetosome formation.
      Homologous genes were found in the genome sequences of M. magnetotacticum and
      magnetic coccus strain MC-1. The MM proteins identified display homology to
      tetratricopeptide repeat proteins (MamA), cation diffusion facilitators (MamB),
      and HtrA-like serine proteases (MamE) or bear no similarity to known proteins
      (MamC and MamD). A major gene cluster containing several magnetosome genes
      (including mamA and mamB) was found to be conserved in all three of the strains
      investigated. The mamAB cluster also contains additional genes that have no known
      homologs in any nonmagnetic organism, suggesting a specific role in magnetosome
      formation.

PMID- 11571159
TI  - Reduction of technetium(VII) by Desulfovibrio fructosovorans is mediated by the
      nickel-iron hydrogenase.
AB  - Resting cells of the sulfate-reducing bacterium Desulfovibrio fructosovorans
      grown in the absence of sulfate had a very high Tc(VII)-reducing activity, which
      led to the formation of an insoluble black precipitate. The involvement of a
      periplasmic hydrogenase in Tc(VII) reduction was indicated (i) by the requirement
      for hydrogen as an electron donor, (ii) by the tolerance of this activity to
      oxygen, and (iii) by the inhibition of this activity by Cu(II). Moreover, a
      mutant carrying a deletion in the nickel-iron hydrogenase operon showed a
      dramatic decrease in the rate of Tc(VII) reduction. The restoration of Tc(VII)
      reduction by complementation of this mutation with nickel-iron hydrogenase genes
      demonstrated the specific involvement of the periplasmic nickel-iron hydrogenase
      in the mechanism in vivo. The Tc(VII)-reducing activity was also observed with
      cell extracts in the presence of hydrogen. Under these conditions, Tc(VII) was
      reduced enzymatically to soluble Tc(V) or precipitated to an insoluble black
      precipitate, depending on the chemical nature of the buffer used. The purified
      nickel-iron hydrogenase performed Tc(VII) reduction and precipitation at high
      rates. These series of genetic and biochemical approaches demonstrated that the
      periplasmic nickel-iron hydrogenase of sulfate-reducing bacteria functions as a
      Tc(VII) reductase. The role of cytochrome c(3) in the mechanism is also
      discussed.

PMID- 11571160
TI  - Conversion of milled pine wood by manganese peroxidase from Phlebia radiata.
AB  - Purified manganese peroxidase (MnP) from the white-rot basidiomycete Phlebia
      radiata was found to convert in vitro milled pine wood (MPW) suspended in an
      aqueous reaction solution containing Tween 20, Mn(2+), Mn-chelating organic acid
      (malonate), and a hydrogen peroxide-generating system (glucose-glucose oxidase).
      The enzymatic attack resulted in the polymerization of lower-molecular-mass,
      soluble wood components and in the partial depolymerization of the insoluble bulk
      of pine wood, as demonstrated by high-performance size exclusion chromatography
      (HPSEC). The surfactant Tween 80 containing unsaturated fatty acid residues
      promoted the disintegration of bulk MPW. HPSEC showed that the depolymerization
      yielded preferentially lignocellulose fragments with a predominant molecular mass
      of ca. 0.5 kDa. MnP from P. radiata (MnP3) turned out to be a stable enzyme
      remaining active for 2 days even at 37 degrees C with vigorous stirring, and 65
      and 35% of the activity applied was retained in Tween 20 and Tween 80 reaction
      mixtures, respectively. In the course of reactions, major part of the Mn-chelator
      malonate was decomposed (85 to 87%), resulting in an increase of pH from 4.4 to
      >6.5. An aromatic nonphenolic lignin structure (beta-O-4 dimer), which is
      normally not attacked by MnP, was oxidizible in the presence of pine wood meal.
      This finding indicates that certain wood components may promote the degradative
      activities of MnP in a way similar to that promoted by Tween 80, unsaturated
      fatty acids, or thiols.

PMID- 11571161
TI  - Survival response and rearrangement of plasmid DNA of Lactococcus lactis during
      long-term starvation.
AB  - The survival response of Lactococcus lactis during long-term starvation was
      investigated. The cells were cultured with different levels of glucose (the sole
      energy source) and either were kept in the resultant spent medium or transferred
      to fresh medium (without glucose) for up to 2 years. The survival of the cells
      during starvation was not dependent on the nature of transition phase, as
      expected, but on the nature of medium in which the cells were kept. The
      proliferation of cells, despite the apparent lack of glucose, could have been due
      to some cells being able to utilize the small amounts of peptides still present
      in the spent medium or to use energy sources provided by the breakup of dead
      cells. The 1- and 2-year-old cultures contained cells with vastly changed
      morphotypes. When these isolates were examined, it was revealed that the original
      plasmids present in the parent were rearranged in a certain way, and an entirely
      new plasmid was generated. Changes were also evident in the chromosomal DNA and
      in gene expression. Furthermore, all of the isolates exhibited a growth advantage
      relative to the parent cells when grown in energy-limiting media. When they were
      tested against different types of stresses, they exhibited a higher resistance
      against the bile salt and hydrogen peroxide stresses compared to the parent.
      Because of the similar changes observed in the 2-year-old isolates, a similar
      survival strategy may be operational in those cells that survive for that length
      of time.

PMID- 11571162
TI  - Cloning, nucleotide sequencing, and functional analysis of a novel, mobile
      cluster of biodegradation genes from Pseudomonas aeruginosa strain JB2.
AB  - We have identified in Pseudomonas aeruginosa strain JB2 a novel cluster of mobile
      genes encoding degradation of hydroxy- and halo-aromatic compounds. Nineteen open
      reading frames were located and, based on sequence similarities, were putatively
      identified as encoding a ring hydroxylating oxygenase (hybABCD), an ATP-binding
      cassette-type transporter, an extradiol ring-cleavage dioxygenase,
      transcriptional regulatory proteins, enzymes mediating chlorocatechol
      degradation, and transposition functions. Expression of hybABCD in Escherichia
      coli cells effected stoichiometric transformation of 2-hydroxybenzoate
      (salicylate) to 2,5-dihydroxybenzoate (gentisate). This activity was predicted
      from sequence similarity to functionally characterized genes, nagAaGHAb from
      Ralstonia sp. strain U2 (S. L. Fuenmayor, M. Wild, A. L. Boyes, and P. A.
      Williams, J. Bacteriol. 180:2522-2530, 1998), and is the second confirmed example
      of salicylate 5-hydroxylase activity effected by an oxygenase outside the
      flavoprotein group. Growth of strain JB2 or Pseudomonas huttiensis strain D1 (an
      organism that had acquired the 2-chlorobenzoate degradation phenotype from strain
      JB2) on benzoate yielded mutants that were unable to grow on salicylate or 2
      chlorobenzoate and that had a deletion encompassing hybABCD and the region cloned
      downstream. The mutants' inability to grow on 2-chlorobenzoate suggested the loss
      of additional genes outside of, but contiguous with, the characterized region.
      Pulsed-field gel electrophoresis revealed a plasmid of >300 kb in strain D1, but
      no plasmids were detected in strain JB2. Hybridization analyses confirmed that
      the entire 26-kb region characterized here was acquired by strain D1 from strain
      JB2 and was located in the chromosome of both organisms. Further studies to
      delineate the element's boundaries and functional characteristics could provide
      new insights into the mechanisms underlying evolution of bacterial genomes in
      general and of catabolic pathways for anthropogenic pollutants in particular.

PMID- 11571163
TI  - Variation in susceptibility to Bacillus thuringiensis toxins among unselected
      strains of Plutella xylostella.
AB  - So far, the only insect that has evolved resistance in the field to Bacillus
      thuringiensis toxins is the diamondback moth (Plutella xylostella). Documentation
      and analysis of resistant strains rely on comparisons with laboratory strains
      that have not been exposed to B. thuringiensis toxins. Previously published
      reports show considerable variation among laboratories in responses of unselected
      laboratory strains to B. thuringiensis toxins. Because different laboratories
      have used different unselected strains, such variation could be caused by
      differences in bioassay methods among laboratories, genetic differences among
      unselected strains, or both. Here we tested three unselected strains against five
      B. thuringiensis toxins (Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ca, and Cry1Da) using two
      bioassay methods. Tests of the LAB-V strain from The Netherlands in different
      laboratories using different bioassay methods yielded only minor differences in
      results. In contrast, side-by-side comparisons revealed major genetic differences
      in susceptibility between strains. Compared with the LAB-V strain, the ROTH
      strain from England was 17- to 170-fold more susceptible to Cry1Aa and Cry1Ac,
      respectively, whereas the LAB-PS strain from Hawaii was 8-fold more susceptible
      to Cry1Ab and 13-fold more susceptible to Cry1Da and did not differ significantly
      from the LAB-V strain in response to Cry1Aa, Cry1Ac, or Cry1Ca. The relative
      potencies of toxins were similar among LAB-V, ROTH, and LAB-PS, with Cry1Ab and
      Cry1Ac being most toxic and Cry1Da being least toxic. Therefore, before choosing
      a standard reference strain upon which to base comparisons, it is highly
      advisable to perform an analysis of variation in susceptibility among field and
      laboratory populations.

PMID- 11571164
TI  - Electropositive filter membrane as an alternative for the elimination of PCR
      inhibitors from sewage and water samples.
AB  - PCR is the best method for the detection of enteric viruses present at low
      concentrations in environmental samples. However, some organic and inorganic
      compounds present in these samples can interfere in the reaction. Many of these
      substances are cytotoxic, too. The ZP60S filter membranes used in addition to
      fluorpentane treatment are quite efficient for virus concentration and
      simultaneous elimination of cytotoxicity from environmental samples. In this
      study, both procedures were used to promote the elimination of reverse
      transcriptase PCR (RT-PCR) inhibitors from sewage and sewage-polluted creek
      water. Samples were subjected separately to each of the following procedures:
      filtration through electropositive filter membranes (ZP60S), organic extraction
      with Vertrel XF, and filtration through ZP60S followed by organic extraction.
      Afterwards, aliquots were experimentally inoculated with rotavirus SA-11 RNA and
      subjected to RT-seminested PCR for amplification of the VP7 gene. Results showed
      that the ZP60S membranes efficiently eliminated the RT-PCR inhibitors from water
      samples. The sample processing method was also applied to 31 in natural sewage
      and creek water samples for detection of naturally occurring rotavirus. A duplex
      seminested PCR was used for the quick detection of couples of the four rotavirus
      genotypes (G1 to G4). Eight samples (25.8%) were positive, and rotavirus
      sequences were not detected in 23 (74.2%). Results were confirmed by direct
      immunoperoxidase method. In summary, the use of electropositive filter membrane
      is appropriate for the elimination of substances that can interfere with RT-PCR,
      obviating additional sample purification methods.

PMID- 11571166
TI  - Determination of pyrimidine dimers in Escherichia coli and Cryptosporidium parvum
      during UV light inactivation, photoreactivation, and dark repair.
AB  - UV inactivation, photoreactivation, and dark repair of Escherichia coli and
      Cryptosporidium parvum were investigated with the endonuclease sensitive site
      (ESS) assay, which can determine UV-induced pyrimidine dimers in the genomic DNA
      of microorganisms. In a 99.9% inactivation of E. coli, high correlation was
      observed between the dose of UV irradiation and the number of pyrimidine dimers
      induced in the DNA of E. coli. The colony-forming ability of E. coli also
      correlated highly with the number of pyrimidine dimers in the DNA, indicating
      that the ESS assay is comparable to the method conventionally used to measure
      colony-forming ability. When E. coli were exposed to fluorescent light after a
      99.9% inactivation by UV irradiation, UV-induced pyrimidine dimers in the DNA
      were continuously repaired and the colony-forming ability recovered gradually.
      When kept in darkness after the UV inactivation, however, E. coli showed neither
      repair of pyrimidine dimers nor recovery of colony-forming ability. When C.
      parvum were exposed to fluorescent light after UV inactivation, UV-induced
      pyrimidine dimers in the DNA were continuously repaired, while no recovery of
      animal infectivity was observed. When kept in darkness after UV inactivation, C.
      parvum also showed no recovery of infectivity in spite of the repair of
      pyrimidine dimers. It was suggested, therefore, that the infectivity of C. parvum
      would not recover either by photoreactivation or by dark repair even after the
      repair of pyrimidine dimers in the genomic DNA.

PMID- 11571165
TI  - Relationships between microbial community structure and hydrochemistry in a
      landfill leachate-polluted aquifer.
AB  - Knowledge about the relationship between microbial community structure and
      hydrogeochemistry (e.g., pollution, redox and degradation processes) in landfill
      leachate-polluted aquifers is required to develop tools for predicting and
      monitoring natural attenuation. In this study analyses of pollutant and redox
      chemistry were conducted in parallel with culture-independent profiling of
      microbial communities present in a well-defined aquifer (Banisveld, The
      Netherlands). Degradation of organic contaminants occurred under iron-reducing
      conditions in the plume of pollution, while upstream of the landfill and above
      the plume denitrification was the dominant redox process. Beneath the plume iron
      reduction occurred. Numerical comparison of 16S ribosomal DNA (rDNA)-based
      denaturing gradient gel electrophoresis (DGGE) profiles of Bacteria and Archaea
      in 29 groundwater samples revealed a clear difference between the microbial
      community structures inside and outside the contaminant plume. A similar
      relationship was not evident in sediment samples. DGGE data were supported by
      sequencing cloned 16S rDNA. Upstream of the landfill members of the beta subclass
      of the class Proteobacteria (beta-proteobacteria) dominated. This group was not
      encountered beneath the landfill, where gram-positive bacteria dominated. Further
      downstream the contribution of gram-positive bacteria to the clone library
      decreased, while the contribution of delta-proteobacteria strongly increased and
      beta-proteobacteria reappeared. The beta-proteobacteria (Acidovorax, Rhodoferax)
      differed considerably from those found upstream (Gallionella, Azoarcus). Direct
      comparisons of cloned 16S rDNA with bands in DGGE profiles revealed that the data
      from each analysis were comparable. A relationship was observed between the
      dominant redox processes and the bacteria identified. In the iron-reducing plume
      members of the family Geobacteraceae made a strong contribution to the microbial
      communities. Because the only known aromatic hydrocarbon-degrading, iron-reducing
      bacteria are Geobacter spp., their occurrence in landfill leachate-contaminated
      aquifers deserves more detailed consideration.

PMID- 11571167
TI  - Diversity of toxic and nontoxic nodularia isolates (cyanobacteria) and filaments
      from the Baltic Sea.
AB  - Cyanobacteria of the genus Nodularia form toxic blooms in brackish waters
      worldwide. In addition, Nodularia spp. are found in benthic, periphytic, and soil
      habitats. The majority of the planktic isolates produce a pentapeptide
      hepatotoxin nodularin. We examined the morphologic, toxicologic, and molecular
      characters of 18 nodularin-producing and nontoxic Nodularia strains to find
      appropriate markers for distinguishing the toxic strains from the nontoxic ones
      in field samples. After classical taxonomy, the examined strains were identified
      as Nodularia sp., Nodularia spumigena, N. baltica, N. harveyana, and N.
      sphaerocarpa. Morphologic characters were ambiguous in terms of distinguishing
      between the toxic and the nontoxic strains. DNA sequences from the short 16S-23S
      rRNA internally transcribed spacer (ITS1-S) and from the phycocyanin operon
      intergenic spacer and its flanking regions (PC-IGS) were different for the toxic
      and the nontoxic strains. Phylogenetic analysis of the ITS1-S and PC-IGS
      sequences from strains identified as N. spumigena, and N. baltica, and N. litorea
      indicated that the division of the planktic Nodularia into the three species is
      not supported by the ITS1-S and PC-IGS sequences. However, the ITS1-S and PC-IGS
      sequences supported the separation of strains designated N. harveyana and N.
      sphaerocarpa from one another and the planktic strains. HaeIII digestion of PCR
      amplified PC-IGS regions of all examined 186 Nodularia filaments collected from
      the Baltic Sea produced a digestion pattern similar to that found in toxic
      isolates. Our results suggest that only one planktic Nodularia species is present
      in the Baltic Sea plankton and that it is nodularin producing.

PMID- 11571168
TI  - Relationship of exo-beta-D-galactofuranosidase kinetic parameters to the number
      of phosphodiesters in Penicillium fellutanum peptidophosphogalactomannan: enzyme
      purification and kinetics of glycopeptide and galactofuran chain hydrolysis.
AB  - Extracellular Penicillium fellutanum exo-beta-D-galactofuranosidase, with a mass
      of 70 kDa, was purified to apparent homogeneity. The enzyme was used to
      investigate the influence of phosphodiesters of the peptidophosphogalactomannans
      pP(2)GM(ii) and pP(25)GM(ii) (containing 2 and 25 phosphodiester residues,
      respectively, per mol of polymer) on the kinetic parameters of galactofuranosyl
      hydrolysis of these two polymers, of 1-O-methyl-beta-D-galactofuranoside, and of
      two galactofuranooligosaccharides. The enzyme did not hydrolyze phosphorylated
      galactose residues of pP(2)GM(ii) or pP(25)GM(ii). The k(cat)/K(m) value for
      pP(25)GM(ii) is 1.7 x 10(3) M(-1) s(-1), that for 1-O-methyl-beta-D
      galactofuranoside is 1.1 x 10(4) M(-1) s(-1), that for pP(2)GM(ii) is 1.7 x 10
      (4) M(-1) s(-1), and those for 5-O-beta-D-galactofuranooligosaccharides with
      degrees of polymerization of 3.4 and 5.5 are 1.7 x 10(5) and 4.1 x 10(5) M(-1) s(
      1), respectively. Variability in the k(cat)/K(m) values is due primarily to
      differences in K(m) values; the k(-1)/k(1) ratio likely provides the most
      influence on K(m). k(cat) increases as the degree of polymerization of
      galactofuranosyl residues increases. Most of the galactofuranosyl and
      phosphocholine residues were removed by day 8 in vivo from pP(x)GM(ii) added to
      day 3 cultures initiated in medium containing 2 mM phosphate but not from those
      initially containing 20 mM phosphate. The filtrates from day 9 cultures initiated
      in 2 mM inorganic phosphate in modified Raulin-Thom medium contained 0.2 mM
      inorganic phosphate and 2.2 U of galactofuranosidase ml(-1)h(-1). No
      galactofuranosidase activity but 15 mM inorganic phosphate was found in filtrates
      from day 9 cultures initiated in 20 mM phosphate. In vivo the rate of
      galactofuranosyl hydrolysis of pP(x)GM(ii) and of related polymers is
      proportional to the k(cat)/K(m) value of each polymer. The kinetic data show that
      the k(cat)/K(m) value increases as the number of phosphodiesters of pP(x)GM(ii)
      decreases, also resulting in an increase in the activity of exo-beta-D
      galactofuranosidase.

PMID- 11571169
TI  - Cross-epithelial hydrogen transfer from the midgut compartment drives
      methanogenesis in the hindgut of cockroaches.
AB  - In the intestinal tracts of animals, methanogenesis from CO(2) and other C(1)
      compounds strictly depends on the supply of electron donors by fermenting
      bacteria, but sources and sinks of reducing equivalents may be spatially
      separated. Microsensor measurements in the intestinal tract of the omnivorous
      cockroach Blaberus sp. showed that molecular hydrogen strongly accumulated in the
      midgut (H(2) partial pressures of 3 to 26 kPa), whereas it was not detectable
      (<0.1 kPa) in the posterior hindgut. Moreover, living cockroaches emitted large
      quantities of CH(4) [105 +/- 49 nmol (g of cockroach)(-1) h(-1)] but only traces
      of H(2). In vitro incubation of isolated gut compartments, however, revealed that
      the midguts produced considerable amounts of H(2), whereas hindguts emitted only
      CH(4) [106 +/- 58 and 71 +/- 50 nmol (g of cockroach)(-1) h(-1), respectively].
      When ligated midgut and hindgut segments were incubated in the same vials,
      methane emission increased by 28% over that of isolated hindguts, whereas only
      traces of H(2) accumulated in the headspace. Radial hydrogen profiles obtained
      under air enriched with H(2) (20 kPa) identified the hindgut as an efficient sink
      for externally supplied H(2). A cross-epithelial transfer of hydrogen from the
      midgut to the hindgut compartment was clearly evidenced by the steep H(2)
      concentration gradients which developed when ligated fragments of midgut and
      hindgut were placed on top of each other-a configuration that simulates the
      situation in vivo. These findings emphasize that it is essential to analyze the
      compartmentalization of the gut and the spatial organization of its microbiota in
      order to understand the functional interactions among different microbial
      populations during digestion.

PMID- 11571170
TI  - Resolution of viable and membrane-compromised bacteria in freshwater and marine
      waters based on analytical flow cytometry and nucleic acid double staining.
AB  - The membrane integrity of a cell is a well-accepted criterion for characterizing
      viable (active or inactive) cells and distinguishing them from damaged and
      membrane-compromised cells. This information is of major importance in studies of
      the function of microbial assemblages in natural environments, in order to assign
      bulk activities measured by various methods to the very active cells that are
      effectively responsible for the observations. To achieve this task for bacteria
      in freshwater and marine waters, we propose a nucleic acid double-staining assay
      based on analytical flow cytometry, which allows us to distinguish viable from
      damaged and membrane-compromised bacteria and to sort out noise and detritus.
      This method is derived from the work of S. Barbesti et al. (Cytometry 40:214-218,
      2000) which was conducted on cultured bacteria. The principle of this approach is
      to use simultaneously a permeant (SYBR Green; Molecular Probes) and an impermeant
      (propidium iodide) probe and to take advantage of the energy transfer which
      occurs between them when both probes are staining nucleic acids. A full quenching
      of the permeant probe fluorescence by the impermeant probe will point to cells
      with a compromised membrane, a partial quenching will indicate cells with a
      slightly damaged membrane, and a lack of quenching will characterize intact
      membrane cells identified as viable. In the present study, this approach has been
      adapted to bacteria in freshwater and marine waters of the Mediterranean region.
      It is fast and easy to use and shows that a large fraction of bacteria with low
      DNA content can be composed of viable cells. Admittedly, limitations stem from
      the unknown behavior of unidentified species present in natural environments
      which may depart from the established permeability properties with respect to the
      fluorescing dyes.

PMID- 11571171
TI  - Group-specific monitoring of phenol hydroxylase genes for a functional assessment
      of phenol-stimulated trichloroethylene bioremediation.
AB  - The sequences of the largest subunit of bacterial multicomponent phenol
      hydroxylases (LmPHs) were compared. It was found that LmPHs formed three
      phylogenetic groups, I, II, and III, corresponding to three previously reported
      kinetic groups, low-K(s) (the half-saturation constant in Haldane's equation for
      trichloroethylene [TCE]), moderate-K(s), and high-K(s) groups. Consensus
      sequences and specific amino acid residues for each group of LmPH were found,
      which facilitated the design of universal and group-specific PCR primers. PCR
      mediated approaches using these primers were applied to analyze phenol/TCE
      degrading populations in TCE-contaminated aquifer soil. It was found that the
      aquifer soil harbored diverse genotypes of LmPH, and the group-specific primers
      successfully amplified LmPH fragments affiliated with each of the three groups.
      Analyses of phenol-degrading bacteria isolated from the aquifer soil confirmed
      the correlation between genotype and phenotype. Competitive PCR assays were used
      to quantify LmPHs belonging to each group during the enrichment of phenol/TCE
      degrading bacteria from the aquifer soil. We found that an enrichment culture
      established by batch phenol feeding expressed low TCE-degrading activity at a TCE
      concentration relevant to the contaminated aquifer (e.g., 0.5 mg liter(-1));
      group II and III LmPHs were predominant in this batch enrichment. In contrast,
      group I LmPHs overgrew an enrichment culture when phenol was fed continuously.
      This enrichment expressed unexpectedly high TCE-degrading activity that was
      comparable to the activity expressed by a pure culture of Methylosinus
      trichosporium OB3b. These results demonstrate the utility of the group-specific
      monitoring of LmPH genes in phenol-stimulated TCE bioremediation. It is also
      suggested that phenol biostimulation could become a powerful TCE bioremediation
      strategy when bacteria possessing group I LmPHs are selectively stimulated.

PMID- 11571173
TI  - TaqMan PCR for detection of Vibrio cholerae O1, O139, non-O1, and non-O139 in
      pure cultures, raw oysters, and synthetic seawater.
AB  - Vibrio cholerae is recognized as a leading human waterborne pathogen. Traditional
      diagnostic testing for Vibrio is not always reliable, because this bacterium can
      enter a viable but nonculturable state. Therefore, nucleic acid-based tests have
      emerged as a useful alternative to traditional enrichment testing. In this
      article, a TaqMan PCR assay is presented for quantitative detection of V.
      cholerae in pure cultures, oysters, and synthetic seawater. Primers and probe
      were designed from the nonclassical hemolysin (hlyA) sequence of V. cholerae
      strains. This probe was applied to DNA from 60 bacterial strains comprising 21
      genera. The TaqMan PCR assay was positive for all of the strains of V. cholerae
      tested and negative for all other species of Vibrio tested. In addition, none of
      the other genera tested was amplified with the TaqMan primers and probe used in
      this study. The results of the TaqMan PCR with raw oysters and spiked with V.
      cholerae serotypes O1 and O139 were comparable to those of pure cultures. The
      sensitivity of the assay was in the range of 6 to 8 CFU g(-1) and 10 CFU ml(-1)
      in spiked raw oyster and synthetic seawater samples, respectively. The total
      assay could be completed in 3 h. Quantification of the Vibrio cells was linear
      over at least 6 log units. The TaqMan probe and primer set developed in this
      study can be used as a rapid screening tool for the presence of V. cholerae in
      oysters and seawater without prior isolation and characterization of the bacteria
      by traditional microbiological methods.

PMID- 11571172
TI  - Generation of metal-binding staphylococci through surface display of
      combinatorially engineered cellulose-binding domains.
AB  - Ni(2+)-binding staphylococci were generated through surface display of
      combinatorially engineered variants of a fungal cellulose-binding domain (CBD)
      from Trichoderma reesei cellulase Cel7A. Novel CBD variants were generated by
      combinatorial protein engineering through the randomization of 11 amino acid
      positions, and eight potentially Ni(2+)-binding CBDs were selected by phage
      display technology. These new variants were subsequently genetically introduced
      into chimeric surface proteins for surface display on Staphylococcus carnosus
      cells. The expressed chimeric proteins were shown to be properly targeted to the
      cell wall of S. carnosus cells, since full-length proteins could be extracted and
      affinity purified. Surface accessibility for the chimeric proteins was
      demonstrated, and furthermore, the engineered CBDs, now devoid of cellulose
      binding capacity, were shown to be functional with regard to metal binding, since
      the recombinant staphylococci had gained Ni(2+)-binding capacity. Potential
      environmental applications for such tailor-made metal-binding bacteria as
      bioadsorbents in biofilters or biosensors are discussed.

PMID- 11571174
TI  - Response of the endophytic diazotroph Gluconacetobacter diazotrophicus on solid
      media to changes in atmospheric partial O(2) pressure.
AB  - Gluconacetobacter diazotrophicus is an N(2)-fixing endophyte isolated from
      sugarcane. G. diazotrophicus was grown on solid medium at atmospheric partial
      O(2) pressures (pO(2)) of 10, 20, and 30 kPa for 5 to 6 days. Using a flowthrough
      gas exchange system, nitrogenase activity and respiration rate were then measured
      at a range of atmospheric pO(2) (5 to 60 kPa). Nitrogenase activity was measured
      by H(2) evolution in N(2)-O(2) and in Ar-O(2), and respiration rate was measured
      by CO(2) evolution in N(2)-O(2). To validate the use of H(2) production as an
      assay for nitrogenase activity, a non-N(2)-fixing (Nif(-)) mutant of G.
      diazotrophicus was tested and found to have a low rate of uptake hydrogenase
      (Hup(+)) activity (0.016 +/- 0.009 micromol of H(2) 10(10) cells(-1) h(-1)) when
      incubated in an atmosphere enriched in H(2). However, Hup(+) activity was not
      detectable under the normal assay conditions used in our experiments. G.
      diazotrophicus fixed nitrogen at all atmospheric pO(2) tested. However, when the
      assay atmospheric pO(2) was below the level at which the colonies had been grown,
      nitrogenase activity was decreased. Optimal atmospheric pO(2) for nitrogenase
      activity was 0 to 20 kPa above the pO(2) at which the bacteria had been grown. As
      atmospheric pO(2) was increased in 10-kPa steps to the highest levels (40 to 60
      kPa), nitrogenase activity decreased in a stepwise manner. Despite the decrease
      in nitrogenase activity as atmospheric pO(2) was increased, respiration rate
      increased marginally. A large single-step increase in atmospheric pO(2) from 20
      to 60 kPa caused a rapid 84% decrease in nitrogenase activity. However, upon
      returning to 20 kPa of O(2), 80% of nitrogenase activity was recovered within 10
      min, indicating a "switch-off/switch-on" O(2) protection mechanism of nitrogenase
      activity. Our study demonstrates that colonies of G. diazotrophicus can fix N(2)
      at a wide range of atmospheric pO(2) and can adapt to maintain nitrogenase
      activity in response to both long-term and short-term changes in atmospheric
      pO(2).

PMID- 11571175
TI  - Expression, gene cloning, and characterization of five novel phytases from four
      basidiomycete fungi: Peniophora lycii, Agrocybe pediades, a Ceriporia sp., and
      Trametes pubescens.
AB  - Phytases catalyze the hydrolysis of phosphomonoester bonds of phytate (myo
      inositol hexakisphosphate), thereby creating lower forms of myo-inositol
      phosphates and inorganic phosphate. In this study, cDNA expression libraries were
      constructed from four basidiomycete fungi (Peniophora lycii, Agrocybe pediades, a
      Ceriporia sp., and Trametes pubescens) and screened for phytase activity in
      yeast. One full-length phytase-encoding cDNA was isolated from each library,
      except for the Ceriporia sp. library where two different phytase-encoding cDNAs
      were found. All five phytases were expressed in Aspergillus oryzae, purified, and
      characterized. The phytases revealed temperature optima between 40 and 60 degrees
      C and pH optima at 5.0 to 6.0, except for the P. lycii phytase, which has a pH
      optimum at 4.0 to 5.0. They exhibited specific activities in the range of 400 to
      1,200 U. mg, of protein(-1) and were capable of hydrolyzing phytate down to myo
      inositol monophosphate. Surprisingly, (1)H nuclear magnetic resonance analysis of
      the hydrolysis of phytate by all five basidiomycete phytases showed a preference
      for initial attack at the 6-phosphate group of phytic acid, a characteristic that
      was believed so far not to be seen with fungal phytases. Accordingly, the
      basidiomycete phytases described here should be grouped as 6-phytases (EC
      3.1.3.26).

PMID- 11571176
TI  - Direct detection of 16S rRNA in soil extracts by using oligonucleotide
      microarrays.
AB  - We report on the development and validation of a simple microarray method for the
      direct detection of intact 16S rRNA from unpurified soil extracts. Total RNAs
      from Geobacter chapellei and Desulfovibrio desulfuricans were hybridized to an
      oligonucleotide array consisting of universal and species-specific 16S rRNA
      probes. PCR-amplified products from Geobacter and Desulfovibrio were easily and
      specifically detected under a range of hybridization times, temperatures, and
      buffers. However, reproducible, specific hybridization and detection of intact
      rRNA could be accomplished only by using a chaperone-detector probe strategy.
      With this knowledge, assay conditions were developed for rRNA detection using a 2
      h hybridization time at room temperature. Hybridization specificity and signal
      intensity were enhanced using fragmented RNA. Formamide was required in the
      hybridization buffer in order to achieve species-specific detection of intact
      rRNA. With the chaperone detection strategy, we were able to specifically
      hybridize and detect G. chapellei 16S rRNA directly from a total-RNA soil
      extract, without further purification or removal of soluble soil constituents.
      The detection sensitivity for G. chapellei 16S rRNA in soil extracts was at least
      0.5 microg of total RNA, representing approximately 7.5 x 10(6) Geobacter cell
      equivalents of RNA. These results suggest that it is now possible to apply
      microarray technology to the direct detection of microorganisms in environmental
      samples, without using PCR.

PMID- 11571177
TI  - Transmission to eels, portals of entry, and putative reservoirs of Vibrio
      vulnificus serovar E (biotype 2).
AB  - Vibrio vulnificus serovar E (formerly biotype 2) is the etiologic agent that is
      responsible for the main infectious disease affecting farmed eels. Although the
      pathogen can theoretically use water as a vehicle for disease transmission, it
      has not been isolated from tank water during epizootics to date. In this work,
      the mode of transmission of the disease to healthy eels, the portals of entry of
      the pathogen into fish, and their putative reservoirs have been investigated by
      means of laboratory and field experiments. Results of the experiments of direct
      and indirect host-to-host transmission, patch contact challenges, and oral-anal
      intubations suggest that water is the prime vehicle for disease transmission and
      that gills are the main portals of entry into the eel body. The pathogen mixed
      with food can also come into the fish through the gastrointestinal tract and
      develop the disease. These conclusions were supported by field data obtained
      during a natural outbreak in which we were able to isolate this microorganism
      from tank water for the first time. The examination of some survivors from
      experimental infections by indirect immunofluorescence and scanning electron
      microscopy showed that V. vulnificus serovar E formed a biofilm-like structure on
      the eel skin surface. In vitro assays demonstrated that the ability of the
      pathogen to colonize both hydrophilic and hydrophobic surfaces was inhibited by
      glucose. The capacity to form biofilms on eel surface could constitute a strategy
      for surviving between epizootics or outbreaks, and coated survivors could act as
      reservoirs for the disease.

PMID- 11571178
TI  - Family- and genus-level 16S rRNA-targeted oligonucleotide probes for ecological
      studies of methanotrophic bacteria.
AB  - Methanotrophic bacteria play a major role in the global carbon cycle, degrade
      xenobiotic pollutants, and have the potential for a variety of biotechnological
      applications. To facilitate ecological studies of these important organisms, we
      developed a suite of oligonucleotide probes for quantitative analysis of
      methanotroph-specific 16S rRNA from environmental samples. Two probes target
      methanotrophs in the family Methylocystaceae (type II methanotrophs) as a group.
      No oligonucleotide signatures that distinguish between the two genera in this
      family, Methylocystis and Methylosinus, were identified. Two other probes target,
      as a single group, a majority of the known methanotrophs belonging to the family
      Methylococcaceae (type I/X methanotrophs). The remaining probes target members of
      individual genera of the Methylococcaceae, including Methylobacter, Methylomonas,
      Methylomicrobium, Methylococcus, and Methylocaldum. One of the family-level
      probes also covers all methanotrophic endosymbionts of marine mollusks for which
      16S rRNA sequences have been published. The two known species of the newly
      described genus Methylosarcina gen. nov. are covered by a probe that otherwise
      targets only members of the closely related genus Methylomicrobium. None of the
      probes covers strains of the newly proposed genera Methylocella and
      "Methylothermus," which are polyphyletic with respect to the recognized
      methanotrophic families. Empirically determined midpoint dissociation
      temperatures were 49 to 57 degrees C for all probes. In dot blot screening
      against RNA from positive- and negative-control strains, the probes were specific
      to their intended targets. The broad coverage and high degree of specificity of
      this new suite of probes will provide more detailed, quantitative information
      about the community structure of methanotrophs in environmental samples than was
      previously available.

PMID- 11571179
TI  - Physiological ecology of Clostridium glycolicum RD-1, an aerotolerant acetogen
      isolated from sea grass roots.
AB  - An anaerobic, H(2)-utilizing bacterium, strain RD-1, was isolated from the
      highest growth-positive dilution series of a root homogenate prepared from the
      sea grass Halodule wrightii. Cells of RD-1 were gram-positive, spore-forming,
      motile rods that were linked by connecting filaments. Acetate was produced in
      stoichiometries indicative of an acetyl coenzyme A (acetyl-CoA) pathway-dependent
      metabolism when RD-1 utilized H(2)-CO(2), formate, lactate, or pyruvate. Growth
      on sugars or ethylene glycol yielded acetate and ethanol as end products. RD-1
      grew at the expense of glucose in the presence of low initial concentrations (up
      to 6% [vol/vol]) of O(2) in the headspace of static, horizontally incubated
      culture tubes; the concentration of O(2) decreased during growth in such
      cultures. Peroxidase, NADH oxidase, and superoxide dismutase activities were
      detected in the cytoplasmic fraction of cells grown in the presence of O(2). In
      comparison to cultures incubated under strictly anoxic conditions, acetate
      production decreased, higher amounts of ethanol were produced, and lactate and
      H(2) became significant end products when RD-1 was grown on glucose in the
      presence of O(2). Similarly, when RD-1 was grown on fructose in the presence of
      elevated salt concentrations, lower amounts of acetate and higher amounts of
      ethanol and H(2) were produced. When the concentration of O(2) in the headspace
      exceeded 1% (vol/vol), supplemental H(2) was not utilized. The 16S rRNA gene of
      RD-1 had a 99.7% sequence similarity to that of Clostridium glycolicum DSM
      1288(T), an organism characterized as a fermentative anaerobe. Comparative
      experiments with C. glycolicum DSM 1288(T) demonstrated that it had negligible
      H(2)- and formate-utilizing capacities. However, carbon monoxide dehydrogenase
      was detected in both RD-1 and C. glycolicum DSM 1288(T). A 91.4% DNA-DNA
      hybridization between the genomic DNA of RD-1 and that of C. glycolicum DSM
      1288(T) confirmed that RD-1 was a strain of C. glycolicum. These results indicate
      that (i) RD-1 metabolizes certain substrates via the acetyl-CoA pathway, (ii) RD
      1 can tolerate and consume limited amounts of O(2), (iii) oxic conditions favor
      the production of ethanol, lactate, and H(2) by RD-1, and (iv) the ability of RD
      1 to cope with limited amounts of O(2) might contribute to its survival in a
      habitat subject to daily gradients of photosynthesis-derived O(2).

PMID- 11571180
TI  - Bulk and rhizosphere soil bacterial communities studied by denaturing gradient
      gel electrophoresis: plant-dependent enrichment and seasonal shifts revealed.
AB  - The bacterial rhizosphere communities of three host plants of the pathogenic
      fungus Verticillium dahliae, field-grown strawberry (Fragaria ananassa Duch.),
      oilseed rape (Brassica napus L.), and potato (Solanum tuberosum L.), were
      analyzed. We aimed to determine the degree to which the rhizosphere effect is
      plant dependent and whether this effect would be increased by growing the same
      crops in two consecutive years. Rhizosphere or soil samples were taken five times
      over the vegetation periods. To allow a cultivation-independent analysis, total
      community DNA was extracted from the microbial pellet recovered from root or soil
      samples. 16S rDNA fragments amplified by PCR from soil or rhizosphere bacterium
      DNA were analyzed by denaturing gradient gel electrophoresis (DGGE). The DGGE
      fingerprints showed plant-dependent shifts in the relative abundance of bacterial
      populations in the rhizosphere which became more pronounced in the second year.
      DGGE patterns of oilseed rape and potato rhizosphere communities were more
      similar to each other than to the strawberry patterns. In both years seasonal
      shifts in the abundance and composition of the bacterial rhizosphere populations
      were observed. Independent of the plant species, the patterns of the first
      sampling times for both years were characterized by the absence of some of the
      bands which became dominant at the following sampling times. Bacillus megaterium
      and Arthrobacter sp. were found as predominant populations in bulk soils.
      Sequencing of dominant bands excised from the rhizosphere patterns revealed that
      6 out of 10 bands resembled gram-positive bacteria. Nocardia populations were
      identified as strawberry-specific bands.

PMID- 11571181
TI  - Diversity of Geotrichum candidum strains isolated from traditional cheesemaking
      fabrications in France.
AB  - The diversity of French fungus-ripened cheeses is due partly to the succession of
      fungi that colonize the cheese during ripening. Geotrichum candidum appears in
      the early stages of ripening on soft cheeses such as Camembert and semihard
      cheeses such as St. Nectaire and Reblochon. Its lipases and proteases promote
      flavor development, and its aminopeptidases reduce bitterness imparted by low
      molecular-weight peptides in cheese. We assessed the genetic diversity of G.
      candidum strains by using random amplification of polymorphic DNA (RAPD)-PCR
      correlated with phenotypic tests for carbon assimilation and salt tolerance.
      Strains were isolated from milk, curd, and cheese collected in seven major
      cheesemaking regions of France. Sixty-four isolates were characterized. We found
      high genetic diversity of G. candidum even within the same cheesemaking regions.
      Strains did not group according to region. All of the strains from the Haute
      Savoie were able to assimilate lactate as the sole source of carbon, while
      lactate assimilation varied among strains from the Auvergne. Strains varied in D
      mannitol assimilation, and none used citrate as the sole source of carbon. Yeast
      like colony morphology predominated in Reblochon, while all of the strains
      isolated from St. Nectaire were filamentous. The RAPD-PCR technique readily
      differentiated Geotrichum fragrans isolated from milk and curd in a St. Nectaire
      cheesemaking facility. This study reveals an enormous diversity of G. candidum
      that has been empirically selected through the centuries by the cheesemakers of
      France.

PMID- 11571182
TI  - Survival of salmonellae on and in tomato plants from the time of inoculation at
      flowering and early stages of fruit development through fruit ripening.
AB  - The fate of salmonellae applied to tomato plants was investigated. Five
      Salmonella serotypes were used to inoculate tomato plants before and after fruits
      set, either by injecting stems with inoculum or brushing flowers with it. Ripe
      tomato fruits were subjected to microbiological analysis. Peptone wash water,
      homogenates of stem scar tissues, and homogenates of fruit pulp were serially
      diluted and plated on bismuth sulfite agar before and after enrichment.
      Presumptive Salmonella colonies were confirmed by serological tests, PCR assay
      using HILA2 primers, and enterobacterial repetitive intergenic consensus PCR. Of
      30 tomatoes harvested from inoculated plants, 11 (37%) were positive for
      Salmonella. Of the Salmonella-positive tomatoes, 43 and 40%, respectively, were
      from plants receiving stem inoculation before and after flower set. Two of eight
      tomatoes produced from inoculated flowers contained Salmonella. Higher
      percentages of surface (82%) and stem scar tissue (73%) samples, compared to pulp
      of Salmonella-positive tomatoes (55%), harbored the pathogen. Of the five
      serotypes in the inoculum, Montevideo was the most persistent, being isolated
      from tomatoes 49 days after inoculation, and Poona was the most dominant, being
      present in 5 of 11 Salmonella-positive tomatoes. Results suggest that Salmonella
      cells survive in or on tomato fruits from the time of inoculation at flowering
      through fruit ripening. Tomato stems and flowers are possible sites at which
      Salmonella may attach and remain viable during fruit development, thus serving as
      routes or reservoirs for contaminating ripened fruit.

PMID- 11571183
TI  - Copper-induced inhibition of growth of Desulfovibrio desulfuricans G20:
      assessment of its toxicity and correlation with those of zinc and lead.
AB  - The toxicity of copper [Cu(II)] to sulfate-reducing bacteria (SRB) was studied by
      using Desulfovibrio desulfuricans G20 in a medium (MTM) developed specifically to
      test metal toxicity to SRB (R. K. Sani, G. Geesey, and B. M. Peyton, Adv.
      Environ. Res. 5:269-276, 2001). The effects of Cu(II) toxicity were observed in
      terms of inhibition in total cell protein, longer lag times, lower specific
      growth rates, and in some cases no measurable growth. At only 6 microM, Cu(II)
      reduced the maximum specific growth rate by 25% and the final cell protein
      concentration by 18% compared to the copper-free control. Inhibition by Cu(II) of
      cell yield and maximum specific growth rate increased with increasing
      concentrations. The Cu(II) concentration causing 50% inhibition in final cell
      protein was evaluated to be 16 microM. A Cu(II) concentration of 13.3 microM
      showed 50% inhibition in maximum specific growth rate. These results clearly show
      significant Cu(II) toxicity to SRB at concentrations that are 100 times lower
      than previously reported. No measurable growth was observed at 30 microM Cu(II)
      even after a prolonged incubation of 384 h. In contrast, Zn(II) and Pb(II), at 16
      and 5 microM, increased lag times by 48 and 72 h, respectively, but yielded final
      cell protein concentrations equivalent to those of the zinc- and lead-free
      controls. Live/dead staining, based on membrane integrity, indicated that while
      Cu(II), Zn(II), and Pb(II) inhibited growth, these metals did not cause a loss of
      D. desulfuricans membrane integrity. The results show that D. desulfuricans in
      the presence of Cu(II) follows a growth pattern clearly different from the
      pattern followed in the presence of Zn(II) or Pb(II). It is therefore likely that
      Cu(II) toxicity proceeds by a mechanism different from that of Zn(II) or Pb(II)
      toxicity.

PMID- 11571184
TI  - The glycogen-bound polyphosphate kinase from Sulfolobus acidocaldarius is
      actually a glycogen synthase.
AB  - Inorganic polyphosphate (polyP) is obtained by the polymerization of the terminal
      phosphate of ATP through the action of the enzyme polyphosphate kinase (PPK).
      Despite the presence of polyP in every living cell, a gene homologous to that of
      known PPKs is missing from the currently sequenced genomes of Eukarya, Archaea,
      and several bacteria. To further study the metabolism of polyP in Archaea, we
      followed the previously published purification procedure for a glycogen-bound
      protein of 57 kDa with PPK as well as glycosyl transferase (GT) activities from
      Sulfolobus acidocaldarius (R. Skorko, J. Osipiuk, and K. O. Stetter, J.
      Bacteriol. 171:5162-5164, 1989). In spite of using recently developed specific
      enzymatic methods to analyze polyP, we could not reproduce the reported PPK
      activity for the 57-kDa protein and the polyP presumed to be the product of the
      reaction most likely corresponded to glycogen-bound ATP under our experimental
      conditions. Furthermore, no PPK activity was found associated to any of the
      proteins bound to the glycogen-protein complex. We cloned the gene corresponding
      to the 57-kDa protein by using reverse genetics and functionally characterized
      it. The predicted product of the gene did not show similarity to any described
      PPK but to archaeal and bacterial glycogen synthases instead. In agreement with
      these results, the recombinant protein showed only GT activity. Interestingly,
      the GT from S. acidocaldarius was phosphorylated in vivo. In conclusion, our
      results convincingly demonstrate that the glycogen-protein complex of S.
      acidocaldarius does not contain a PPK activity and that what was previously
      reported as being glycogen-bound PPK is a bacterial enzyme-like thermostable
      glycogen synthase.

PMID- 11571185
TI  - Development of a combined selection and enrichment PCR procedure for Clostridium
      botulinum Types B, E, and F and its use to determine prevalence in fecal samples
      from slaughtered pigs.
AB  - A specific and sensitive combined selection and enrichment PCR procedure was
      developed for the detection of Clostridium botulinum types B, E, and F in fecal
      samples from slaughtered pigs. Two enrichment PCR assays, using the DNA
      polymerase rTth, were constructed. One assay was specific for the type B
      neurotoxin gene, and the other assay was specific for the type E and F neurotoxin
      genes. Based on examination of 29 strains of C. botulinum, 16 strains of other
      Clostridium spp., and 48 non-Clostridium strains, it was concluded that the two
      PCR assays detect C. botulinum types B, E, and F specifically. Sample preparation
      prior to the PCR was based on heat treatment of feces homogenate at 70 degrees C
      for 10 min, enrichment in tryptone-peptone-glucose-yeast extract broth at 30
      degrees C for 18 h, and DNA extraction. The detection limits after sample
      preparation were established as being 10 spores per g of fecal sample for
      nonproteolytic type B, and 3.0 x 10(3) spores per g of fecal sample for type E
      and nonproteolytic type F with a detection probability of 95%. Seventy-eight pig
      fecal samples collected from slaughter houses were analyzed according to the
      combined selection and enrichment PCR procedure, and 62% were found to be PCR
      positive with respect to the type B neurotoxin gene. No samples were positive
      regarding the type E and F neurotoxin genes, indicating a prevalence of less than
      1.3%. Thirty-four (71%) of the positive fecal samples had a spore load of less
      than 4 spores per g. Statistical analysis showed that both rearing conditions
      (outdoors and indoors) and seasonal variation (summer and winter) had significant
      effects on the prevalence of C. botulinum type B, whereas the effects of
      geographical location (southern and central Sweden) were less significant.

PMID- 11571186
TI  - Infection of Acanthamoeba polyphaga with Simkania negevensis and S. negevensis
      survival within amoebal cysts.
AB  - Simkania negevensis, a novel microorganism belonging to the family Simkaniaceae
      in the order Chlamydiales, has an intracellular developmental cycle during which
      two morphological entities, elementary bodies (EB) and reticulate bodies (RB),
      are seen by electron microscopy. Rates of seropositivity to the organism are high
      in certain population groups, and S. negevensis has been associated with
      respiratory illness in humans. This study reports for the first time the ability
      of S. negevensis to survive and grow inside Acanthamoeba polyphaga in addition to
      its known ability to grow in cell cultures of human or simian origin. Infectivity
      of S. negevensis and growth in amoebae were monitored by immunoperoxidase assays.
      Long-term persistence and exponential growth of S. negevensis in amoebal
      trophozoites were demonstrated by infectivity assays and by electron microscopy.
      EB and dividing RB of S. negevensis were observed within inclusion bodies inside
      A. polyphaga. When S. negevensis-infected A. polyphaga amoebae were exposed to
      adverse conditions resulting in encystation of the amoebae, several possible
      outcomes were observed: cysts containing both normal amoebic cytoplasm and S.
      negevensis; cysts in which S. negevensis cells were relegated to the space
      between cyst walls; and cysts containing S. negevensis, but apparently lacking
      amoebal cytoplasm. S. negevensis within dried amoebal cysts was capable of long
      term survival. The possibility that amoebae may have a role in natural
      transmission of S. negevensis needs to be investigated.

PMID- 11571187
TI  - Stable-isotope-based labeling of styrene-degrading microorganisms in biofilters.
AB  - Deuterated styrene ([(2)H(8)]styrene) was used as a tracer in combination with
      phospholipid fatty acid (PLFA) analysis for characterization of styrene-degrading
      microbial populations of biofilters used for treatment of waste gases. Deuterated
      fatty acids were detected and quantified by gas chromatography-mass spectrometry.
      The method was evaluated with pure cultures of styrene-degrading bacteria and
      defined mixed cultures of styrene degraders and non-styrene-degrading organisms.
      Incubation of styrene degraders for 3 days with [(2)H(8)]styrene led to fatty
      acids consisting of up to 90% deuterated molecules. Mixed-culture experiments
      showed that specific labeling of styrene-degrading strains and only weak labeling
      of fatty acids of non-styrene-degrading organisms occurred after incubation with
      [(2)H(8)]styrene for up to 7 days. Analysis of actively degrading filter material
      from an experimental biofilter and a full-scale biofilter by this method showed
      that there were differences in the patterns of labeled fatty acids. For the
      experimental biofilter the fatty acids with largest amounts of labeled molecules
      were palmitic acid (16:0), 9,10-methylenehexadecanoic acid (17:0 cyclo9-10), and
      vaccenic acid (18:1 cis11). These lipid markers indicated that styrene was
      degraded by organisms with a Pseudomonas-like fatty acid profile. In contrast,
      the most intensively labeled fatty acids of the full-scale biofilter sample were
      palmitic acid and cis-11-hexadecenoic acid (16:1 cis11), indicating that an
      unknown styrene-degrading taxon was present. Iso-, anteiso-, and 10-methyl
      branched fatty acids showed no or weak labeling. Therefore, we found no
      indication that styrene was degraded by organisms with methyl-branched fatty
      fatty acids, such as Xanthomonas, Bacillus, Streptomyces, or Gordonia spp.

PMID- 11571188
TI  - Genetic and functional analysis of the tbc operons for catabolism of alkyl- and
      chloroaromatic compounds in Burkholderia sp. strain JS150.
AB  - Burkholderia sp. strain JS150 is able to metabolize a wide range of alkyl-and
      chloroaromatic hydrocarbons through multiple, apparently redundant catabolic
      pathways. Previous research has shown that strain JS150 is able to synthesize
      enzymes for multiple upper pathways as well as multiple lower pathways to
      accommodate variously substituted catechols that result from degradation of
      complex mixtures of monoaromatic compounds. We report here the genetic
      organization and functional characterization of a gene cluster, designated tbc
      (for toluene, benzene, and chlorobenzene utilization), which has been cloned as a
      14.3-kb DNA fragment from strain JS150 into vector pRO1727. The cloned DNA
      fragment expressed in Pseudomonas aeruginosa PAO1c allowed the recombinant to
      grow on toluene or benzene and to transform chlorobenzene, trichloroethylene,
      phenol, and cresols. The tbc genes are organized into two divergently transcribed
      operons, tbc1 and tbc2, each comprised of six open reading frames. Similarity
      searches of databases revealed that the tbc1 and tbc2 genes showed significant
      homology to multicomponent cresol and phenol hydroxylases and to toluene and
      benzene monooxygenases, respectively. Deletion mutagenesis and product analysis
      were used to demonstrate that tbc2 plays a role in the initial catabolism of the
      unactivated alkyl- or chloroaromatic substrate and that the tbc1 gene products
      play a role in the catabolism of the first metabolite that results from
      transformation of the initial substrate. Phylogenetic analysis was used to
      compare individual components of these tbc monooxygenases with similar sequences
      in the databases. These results provide further evidence for the existence of
      multiple, functionally redundant alkyl- and chloroaromatic monooxygenases in
      strain JS150.

PMID- 11571189
TI  - Cloning and genetic characterization of dca genes required for beta-oxidation of
      straight-chain dicarboxylic acids in Acinetobacter sp. strain ADP1.
AB  - A previous study of deletions in the protocatechuate (pca) region of the
      Acinetobacter sp. strain ADP1 chromosome revealed that genes required for
      utilization of the six-carbon dicarboxylic acid, adipic acid, are linked to the
      pca structural genes. To investigate the genes involved in adipate catabolism, a
      33.8-kb SacI fragment, which corrects a deletion spanning this region, was
      cloned. In addition to containing known pca, qui, and pob genes (for
      protocatechuate, quinate, and 4-hydroxybenzoate dissimilation), clone pZR8000
      contained 10 kb of DNA which was the subject of this investigation. A mutant
      strain of Escherichia coli DH5alpha, strain EDP1, was isolated that was able to
      utilize protocatechuate and 4-hydroxybenzoate as growth substrates when EDP1
      cells contained pZR8000. Sequence analysis of the new region of DNA on pZR8000
      revealed open reading frames predicted to be involved in beta-oxidation.
      Knockouts of three genes implicated in beta-oxidation steps were introduced into
      the chromosome of Acinetobacter sp. strain ADP1. Each of the mutants was unable
      to grow with adipate. Because the mutants were affected in their ability to
      utilize additional saturated, straight-chain dicarboxylic acids, the newly
      discovered 10 kb of DNA was termed the dca (dicarboxylic acid) region. Mutant
      strains included one with a deletion in dcaA (encoding an acyl coenzyme A [acyl
      CoA] dehydrogenase homolog), one with a deletion in dcaE (encoding an enoyl-CoA
      hydratase homolog), and one with a deletion in dcaH (encoding a hydroxyacyl-CoA
      dehydrogenase homolog). Data on the dca region should help us probe the
      functional significance and interrelationships of clustered genetic elements in
      this section of the Acinetobacter chromosome.

PMID- 11571190
TI  - Streptococcus suis serotypes characterized by analysis of chaperonin 60 gene
      sequences.
AB  - Streptococcus suis is an important pathogen of swine which occasionally infects
      humans as well. There are 35 serotypes known for this organism, and it would be
      desirable to develop rapid methods methods to identify and differentiate the
      strains of this species. To that effect, partial chaperonin 60 gene sequences
      were determined for the 35 serotype reference strains of S. suis. Analysis of a
      pairwise distance matrix showed that the distances ranged from 0 to 0.275 when
      values were calculated by the maximum-likelihood method. For five of the strains
      the distances from serotype 1 were greater than 0.1, and for two of these strains
      the distances were were more than 0.25, suggesting that they belong to a
      different species. Most of the nucleotide differences were silent; alignment of
      protein sequences showed that there were only 11 distinct sequences for the 35
      strains under study. The chaperonin 60 gene phylogenetic tree was similar to the
      previously published tree based on 16S rRNA sequences, and it was also observed
      that strains with identical chaperonin 60 gene sequences tended to have identical
      16S rRNA sequences. The chaperonin 60 gene sequences provided a higher level of
      discrimination between serotypes than the 16S RNA sequences provided and could
      form the basis for a diagnostic protocol.

PMID- 11571191
TI  - Isolation and characterization of intracellular protein inclusions produced by
      the entomopathogenic bacterium Photorhabdus luminescens.
AB  - Cells of the entomopathogenic bacterium Photorhabdus luminescens contain two
      types of morphologically distinct crystalline inclusion proteins. The larger
      rectangular inclusion (type 1) and a smaller bipyramid-shaped inclusion (type 2)
      were purified from cell lysates by differential centrifugation and isopycnic
      density gradient centrifugation. Both structures are composed of protein and are
      readily soluble at pH 11 and 4 in 1% sodium dodecyl sulfate (SDS) and in 8 M
      urea. Electrophoretic analysis reveals that each inclusion is composed of a
      single protein subunit with a molecular mass of 11,000 Da. The proteins differ in
      amino acid composition, protease digestion pattern, and immunological cross
      reactivity. The protein inclusions are first visible in the cells at the time of
      late exponential growth. Western blot analyses showed that the proteins appeared
      in cells during mid- to late exponential growth. When at maximum size in
      stationary-phase cells, the proteins constitute 40% of the total cellular
      protein. The protein inclusions are not used during long-term starvation of the
      cells and were not toxic when injected into or fed to Galleria mellonella larvae.

PMID- 11571192
TI  - Stable hydrogen and carbon isotope fractionation during microbial toluene
      degradation: mechanistic and environmental aspects.
AB  - Primary features of hydrogen and carbon isotope fractionation during toluene
      degradation were studied to evaluate if analysis of isotope signatures can be
      used as a tool to monitor biodegradation in contaminated aquifers. D/H hydrogen
      isotope fractionation during microbial degradation of toluene was measured by gas
      chromatography. Per-deuterated toluene-d(8) and nonlabeled toluene were supplied
      in equal amounts as growth substrates, and kinetic isotope fractionation was
      calculated from the shift of the molar ratios of toluene-d(8) and nondeuterated
      toluene. The D/H isotope fractionation varied slightly for sulfate-reducing
      strain TRM1 (slope of curve [b] = -1.219), Desulfobacterium cetonicum (b = 
      1.196), Thauera aromatica (b = -0.816), and Geobacter metallireducens (b = 
      1.004) and was greater for the aerobic bacterium Pseudomonas putida mt-2 (b = 
      2.667). The D/H isotope fractionation was 3 orders of magnitude greater than the
      (13)C/(12)C carbon isotope fractionation reported previously. Hydrogen isotope
      fractionation with nonlabeled toluene was 1.7 and 6 times less than isotope
      fractionation with per-deuterated toluene-d(8) and nonlabeled toluene for sulfate
      reducing strain TRM1 (b = -0.728) and D. cetonicum (b = -0.198), respectively.
      Carbon and hydrogen isotope fractionation during toluene degradation by D.
      cetonicum remained constant over a growth temperature range of 15 to 37 degrees C
      but varied slightly during degradation by P. putida mt-2, which showed maximum
      hydrogen isotope fractionation at 20 degrees C (b = -4.086) and minimum
      fractionation at 35 degrees C (b = -2.138). D/H isotope fractionation was
      observed only if the deuterium label was located at the methyl group of the
      toluene molecule which is the site of the initial enzymatic attack on the
      substrate by the bacterial strains investigated in this study. Use of ring
      labeled toluene-d(5) in combination with nondeuterated toluene did not lead to
      significant D/H isotope fractionation. The activity of the first enzyme in the
      anaerobic toluene degradation pathway, benzylsuccinate synthase, was measured in
      cell extracts of D. cetonicum with an initial activity of 3.63 mU (mg of
      protein)(-1). The D/H isotope fractionation (b = -1.580) was 30% greater than
      that in growth experiments with D. cetonicum. Mass spectroscopic analysis of the
      product benzylsuccinate showed that H atoms abstracted from the toluene molecules
      by the enzyme were retained in the same molecules after the product was released.
      Our findings revealed that the use of deuterium-labeled toluene was appropriate
      for studying basic features of D/H isotope fractionation. Similar D/H
      fractionation factors for toluene degradation by anaerobic bacteria, the lack of
      significant temperature dependence, and the strong fractionation suggest that
      analysis of D/H fractionation can be used as a sensitive tool to assess
      degradation activities. Identification of the first enzyme reaction in the
      pathway as the major fractionating step provides a basis for linking observed
      isotope fractionation to biochemical reactions.

PMID- 11571193
TI  - Detection and enumeration of methanotrophs in acidic Sphagnum peat by 16S rRNA
      fluorescence in situ hybridization, including the use of newly developed
      oligonucleotide probes for Methylocella palustris.
AB  - Two 16S rRNA-targeted oligonucleotide probes, Mcell-1026 and Mcell-181, were
      developed for specific detection of the acidophilic methanotroph Methylocella
      palustris using fluorescence in situ hybridization (FISH). The fluorescence
      signal of probe Mcell-181 was enhanced by its combined application with the
      oligonucleotide helper probe H158. Mcell-1026 and Mcell-181, as well as 16S rRNA
      oligonucleotide probes with reported group specificity for either type I
      methanotrophs (probes M-84 and M-705) or the Methylosinus/Methylocystis group of
      type II methanotrophs (probes MA-221 and M-450), were used in FISH to determine
      the abundance of distinct methanotroph groups in a Sphagnum peat sample of pH
      4.2. M. palustris was enumerated at greater than 10(6) cells per g of peat (wet
      weight), while the detectable population size of type I methanotrophs was three
      orders of magnitude below the population level of M. palustris. The cell counts
      with probe MA-221 suggested that only 10(4) type II methanotrophs per g of peat
      (wet weight) were present, while the use of probe M-450 revealed more than 10(6)
      type II methanotroph cells per g of the same samples. This discrepancy was due to
      the fact that probe M-450 targets almost all currently known strains of
      Methylosinus and Methylocystis, whereas probe MA-221, originally described as
      group specific, does not detect a large proportion of Methylocystis strains. The
      total number of methanotrophic bacteria detected by FISH was 3.0 (+/-0.2) x 10(6)
      cells per g (wet weight) of peat. This was about 0.8% of the total bacterial cell
      number. Thus, our study clearly suggests that M. palustris and a defined
      population of Methylocystis spp. were the predominant methanotrophs detectable by
      FISH in an acidic Sphagnum peat bog.

PMID- 11571194
TI  - New additive for culture media for rapid identification of aflatoxin-producing
      Aspergillus strains.
AB  - A new reliable, fast, and simple method for the detection of aflatoxigenic
      Aspergillus strains, consisting of the addition of a cyclodextrin (a methylated
      beta-cyclodextrin derivative) to common media used for testing mycotoxin
      production ability, was developed. We propose the use of this compound as an
      additive for fungal culture media to enhance the natural fluorescence of
      aflatoxins. The production of aflatoxins coincided with the presence of a bright
      blue or blue-green fluorescent area surrounding colonies when observed under long
      wavelength (365-nm) UV light after 3 days of incubation at 28 degrees C. The
      presence of aflatoxins was confirmed by extracting the medium with chloroform and
      examining the extracts by high-pressure liquid chromatography with fluorescence
      detection.

PMID- 11571195
TI  - Fluorescent Amplified Fragment Length Polymorphism Analysis of Norwegian Bacillus
      cereus and Bacillus thuringiensis Soil Isolates.
AB  - We examined 154 Norwegian B. cereus and B. thuringiensis soil isolates (collected
      from five different locations), 8 B. cereus and 2 B. thuringiensis reference
      strains, and 2 Bacillus anthracis strains by using fluorescent amplified fragment
      length polymorphism (AFLP). We employed a novel fragment identification approach
      based on a hierarchical agglomerative clustering routine that identifies
      fragments in an automated fashion. No method is free of error, and we identified
      the major sources so that experiments can be designed to minimize its effect.
      Phylogenetic analysis of the fluorescent AFLP results reveals five genetic groups
      in these group 1 bacilli. The ATCC reference strains were restricted to two of
      the genetic groups, clearly not representative of the diversity in these
      bacteria. Both B. anthracis strains analyzed were closely related and affiliated
      with a B. cereus milk isolate (ATCC 4342) and a B. cereus human pathogenic strain
      (periodontitis). Across the entire study, pathogenic strains, including B.
      anthracis, were more closely related to one another than to the environmental
      isolates. Eight strains representing the five distinct phylogenetic clusters were
      further analyzed by comparison of their 16S rRNA gene sequences to confirm the
      phylogenetic status of these groups. This analysis was consistent with the AFLP
      analysis, although of much lower resolution. The innovation of automated genotype
      analysis by using a replicated and statistical approach to fragment
      identification will allow very large sample analyses in the future.

PMID- 11571196
TI  - Physical and metabolic interactions of Pseudomonas sp. strain JA5-B45 and
      Rhodococcus sp. strain F9-D79 during growth on crude oil and effect of a chemical
      surfactant on them.
AB  - Methods to enhance crude oil biodegradation by mixed bacterial cultures, for
      example, (bio)surfactant addition, are complicated by the diversity of microbial
      populations within a given culture. The physical and metabolic interactions
      between Rhodococcus sp. strain F9-D79 and Pseudomonas sp. strain JA5-B45 were
      examined during growth on Bow River crude oil. The effects of a nonionic chemical
      surfactant, Igepal CO-630 (nonylphenol ethoxylate), also were evaluated. Strain
      F9-D79 grew attached to the oil-water interface and produced a mycolic acid
      containing capsule. Crude oil emulsification and surface activity were associated
      with the cellular fraction. Strain JA5-B45 grew in the aqueous phase and was
      unable to emulsify oil, but cell-free supernatants mediated kerosene-water
      emulsion formation. In coculture, stable emulsions were formed and strain JA5-B45
      had an affinity for the capsule produced by strain F9-D79. Igepal CO-630
      inhibited F9-D79 cells from adhering to the interface, and cells grew dispersed
      in the aqueous phase as 0.5-microm cocci rather than 2.5-microm rods. The
      surfactant increased total petroleum hydrocarbon removal by strain JA5-B45 from 4
      to 22% and included both saturated compounds and aromatics. In coculture, TPH
      removal increased from 13 to 40% following surfactant addition. The culture pH
      normally increased from 7.0 to between 7.5 and 8.5, although addition of Igepal
      CO-630 to F9-D79 cultures resulted in a drop to pH 5.5. We suggest a dual role
      for the nonylphenol ethoxylate surfactant in the coculture: (i) to improve
      hydrocarbon uptake by strain JA5-B45 through emulsification and (ii) to prevent
      strain F9-D79 from adhering to the oil-water interface, indirectly increasing
      hydrocarbon availability. These varied effects on hydrocarbon biodegradation
      could explain some of the known diversity of surfactant effects.

PMID- 11571197
TI  - Axial differences in community structure of Crenarchaeota and Euryarchaeota in
      the highly compartmentalized gut of the soil-feeding termite Cubitermes
      orthognathus.
AB  - Methanogenesis represents an important electron sink reaction in the hindgut of
      soil-feeding termites. This is the first comprehensive analysis of the archaeal
      community structure within the highly compartmentalized intestinal tract of a
      humivorous insect, combining clonal analysis and terminal restriction fragment (T
      RF) length polymorphism (T-RFLP) fingerprinting of the archaeal communities in
      the different gut compartments of Cubitermes orthognathus. We found that the
      morphological and physicochemical heterogeneity of the gut is reflected in a
      large phylogenetic diversity and pronounced axial differences in the composition
      of the archaeal gut microbiota, notably among those clones or ribotypes that
      could be assigned to methanogenic taxa. Comparative analysis of the relative
      frequencies of different archaeal lineages among the small-subunit rRNA gene (SSU
      rDNA) clones and their corresponding T-RF indicated that the archaeal community
      in the anterior, extremely alkaline hindgut compartment (P1) consists mainly of
      members of the Methanosarcinaceae, whereas Methanobacteriaceae and
      Methanomicrobiales predominate in the subsequent, more posterior compartments
      (P3/4a and P4b). The relative abundance of Thermoplasmales increased towards the
      rectum (P5). SSU rDNA sequences representing Crenarchaeota, which have not yet
      been reported to occur in the intestinal tracts of arthropods, were detected in
      all gut sections. We discuss how the spatial distribution of methanogenic
      populations may be linked to axial heterogeneity in the physicochemical gut
      conditions and to functional adaptations to their respective ecological niches.

PMID- 11571198
TI  - Detection of indigenous Halobacillus populations in damaged ancient wall
      paintings and building materials: molecular monitoring and cultivation.
AB  - Several moderately halophilic gram-positive, spore-forming bacteria have been
      isolated by conventional enrichment cultures from damaged medieval wall paintings
      and building materials. Enrichment and isolation were monitored by denaturing
      gradient gel electrophoresis and fluorescent in situ hybridization. 16S ribosomal
      DNA analysis showed that the bacteria are most closely related to Halobacillus
      litoralis. DNA-DNA reassociation experiments identified the isolates as a
      population of hitherto unknown Halobacillus species.

PMID- 11571199
TI  - Assessing the diversity of marine bacterial beta-glucosidases by capillary
      electrophoresis zymography.
AB  - We propose a new method for the fast separation and detection of beta
      glucosidases in environmental samples. With this approach, beta-glucosidases
      extracted from bacteria are evidenced by substrate-incorporated capillary
      electrophoresis (CE zymography) and their kinetic parameters can be determined by
      repeated injections using different substrate concentrations. Preliminary results
      obtained with natural bacterial communities from the coastal North Sea suggest
      that the diversity of beta-glucosidases in the marine environment might be much
      higher than previously observed.

PMID- 11571200
TI  - Variation in resistance to high hydrostatic pressure and rpoS heterogeneity in
      natural isolates of Escherichia coli O157:H7.
AB  - Several natural isolates of Escherichia coli O157:H7 have previously been shown
      to exhibit stationary-phase-dependent variation in their resistance to
      inactivation by high hydrostatic pressure. In this report we demonstrate that
      loss of the stationary-phase-inducible sigma factor RpoS resulted in decreased
      resistance to pressure in E. coli O157:H7 and in a commensal strain. Furthermore,
      variation in the RpoS activity of the natural isolates of O157:H7 correlated with
      the pressure resistance of those strains. Heterogeneity was noted in the rpoS
      alleles of the natural isolates that may explain the differences in RpoS
      activity. These results are consistent with a role for rpoS in mediating
      resistance to high hydrostatic pressure in E. coli O157:H7.

PMID- 11571201
TI  - Evidence for detachment of indigenous bacteria from aquifer sediment in response
      to arrival of injected bacteria.
AB  - Two bacterial strains isolated from the aquifer underlying Oyster, Va., were
      recently injected into the aquifer and monitored using ferrographic capture, a
      high-resolution immunomagnetic technique. Injected cells were enumerated on the
      basis of a vital fluorescence stain, whereas total cell numbers (stained target
      cells plus unstained target and antigenically similar indigenous bacteria) were
      identified by cell outlines emanating from fluorophore-conjugated antibodies to
      the two target strains. The arrival of injected bacteria at the majority of
      monitored sampling ports was accompanied by simultaneous temporary increases in
      unstained cell counts that outnumbered the injected bacteria by 2- to 100-fold.
      The origin and mechanism of appearance of the unstained cells are considered.

PMID- 11571202
TI  - Availability of glutamate and arginine during acid challenge determines cell
      density-dependent survival phenotype of Escherichia coli strains.
AB  - The cell density-dependent acid sensitivity phenotypes of Escherichia coli
      strains K-12 and O157:H7 were examined with reference to three possible
      mechanisms of acid resistance. There was no evidence of any diffusible substance
      released from dead cells which could influence the cell density-dependent acid
      survival phenotype. Instead, cell density-dependent acid survival phenotype was
      associated with induction of glutamate- and arginine-decarboxylase acid survival
      pathways and concomitant availability of glutamate and arginine during acid
      challenge.

PMID- 11571203
TI  - Isolation of an aldehyde dehydrogenase involved in the oxidation of
      fluoroacetaldehyde to fluoroacetate in Streptomyces cattleya.
AB  - Streptomyces cattleya is unusual in that it produces fluoroacetate and 4
      fluorothreonine as secondary metabolites. We now report the isolation of an
      NAD(+)-dependent fluoroacetaldehyde dehydrogenase from S. cattleya that mediates
      the oxidation of fluoroacetaldehyde to fluoroacetate. This is the first enzyme to
      be identified that is directly involved in fluorometabolite biosynthesis.
      Production of the enzyme begins in late exponential growth and continues into the
      stationary phase. Measurement of kinetic parameters shows that the enzyme has a
      high affinity for fluoroacetaldehyde and glycoaldehyde, but not acetaldehyde.

PMID- 11571204
TI  - Isolation of methyl parathion-degrading strain M6 and cloning of the methyl
      parathion hydrolase gene.
AB  - A degradative bacterium, M6, was isolated and presumptively identified as
      Plesiomonas sp. strain M6 was able to hydrolyze methyl parathion to p
      nitrophenol. A novel organophosphate hydrolase gene designated mpd was selected
      from its genomic library prepared by shotgun cloning. The nucleotide sequence of
      the mpd gene was determined. The gene could be effectively expressed in
      Escherichia coli.

PMID- 11571205
TI  - Distinct combinations of Borrelia burgdorferi sensu lato genospecies found in
      individual questing ticks from Europe.
AB  - The genetic diversity of Borrelia burgdorferi sensu lato was assessed in
      individual adult Ixodes ricinus ticks from Europe by direct PCR amplification of
      spirochetal DNA followed by genospecies-specific hybridization. Analysis of mixed
      infections in the ticks showed that B. garinii and B. valaisiana segregate from
      B. afzelii. This and previous findings suggest that host complement interacts
      with spirochetes in the tick, thereby playing an important role in the ecology of
      Lyme borreliosis.

PMID- 11571206
TI  - Vancomycin-resistant Enterococcus spp. isolated from wastewater and chicken feces
      in the United States.
AB  - Vancomycin-resistant Enterococcus spp. (VRE) were isolated from sewage and
      chicken feces but not from other animal fecal sources (dog, cow, and pig) or from
      surface waters tested. VRE from hospital wastewater were resistant to > or =20
      microg of vancomycin/ml and possessed the vanA gene. VRE from residential
      wastewater and chicken feces were resistant to 3 to 5 microg of vancomycin/ml and
      possessed the vanC gene.

PMID- 11571207
TI  - Clonal populations of thermotolerant Enterobacteriaceae in recreational water and
      their potential interference with fecal Escherichia coli counts.
AB  - Bacterial strains were isolated from beach water samples using the original
      Environmental Protection Agency method for Escherichia coli enumeration and
      analyzed by pulsed-field gel electrophoresis (PFGE). Identical PFGE patterns were
      found for numerous isolates from 4 of the 9 days sampled, suggesting
      environmental replication. 16S rRNA gene sequencing, API 20E biochemical testing,
      and the absence of beta-glucuronidase activity revealed that these clonal
      isolates were Klebsiella, Citrobacter, and Enterobacter spp. In contrast, 82% of
      the nonclonal isolates from water samples were confirmed to be E. coli, and 16%
      were identified as other fecal coliforms. These nonclonal isolates produced a
      diverse range of PFGE patterns similar to those of isolates obtained directly
      from untreated sewage and gull droppings. beta-Glucuronidase activity was
      critical in distinguishing E. coli from other fecal coliforms, particularly for
      the clonal isolates. These findings demonstrate that E. coli is a better
      indicator of fecal pollution than fecal coliforms, which may replicate in the
      environment and falsely elevate indicator organism levels.

PMID- 11571209
TI  - Gene microarrays and experimental demyelinating disease: a tool to enhance
      serendipity.

PMID- 11571208
TI  - Comparative study of bacterial groups within the human cecal and fecal
      microbiota.
AB  - The composition of the human cecal microbiota is poorly known because of sampling
      difficulties. Samples of cecal fluid from eight subjects were collected via an
      intestinal tube. Feces were also collected. Total anaerobes, facultative
      anaerobes, bifidobacteria, and Bacteroides were enumerated by culture methods,
      and the predominant phylogenetic groups were quantified by molecular
      hybridization using a set of six rRNA-targeted probes. The numbers of strict
      anaerobes, bifidobacteria, Bacteroides, and members of the Clostridium coccoides
      group and Clostridium leptum subgroup were lower in the cecum. Facultative
      anaerobes represented 25% of total bacteria in the cecum versus 1% in the feces.

PMID- 11571210
TI  - A systematic review of the frequency and prognosis of arteriovenous malformations
      of the brain in adults.
AB  - By systematically reviewing the literature, we have found that there is very
      little information about the frequency and clinical course of arteriovenous
      malformations (AVMs) of the brain in adults because the methods of most studies
      have been flawed, and AVMs tend to be treated once they are discovered. The
      incidence of AVMs is approximately 1 per 100 000 per year in unselected
      populations, and the point prevalence in adults is approximately 18 per 100 000.
      AVMs account for between 1 and 2% of all strokes, 3% of strokes in young adults,
      9% of subarachnoid haemorrhages and, of all primary intracerebral haemorrhages,
      they are responsible for 4% overall, but for as much as one-third in young
      adults. AVMs are far less common causes of first presentations with unprovoked
      seizures (1%), and of people presenting with headaches in the absence of
      neurological signs (0.3%). At the time of detection, at least 15% of people
      affected by AVMs are asymptomatic, about one-fifth present with seizures and for
      approximately two-thirds of them the dominant mode of presentation is with
      intracranial haemorrhage. The limited high quality data available on prognosis
      suggest that long-term crude annual case fatality is 1-1.5%, the crude annual
      risk of first occurrence of haemorrhage from an unruptured AVM is approximately
      2%, but the risk of recurrent haemorrhage may be as high as 18% in the first
      year, with uncertainty about the risk thereafter. For untreated AVMs, the annual
      risk of developing de novo seizures is 1%. There is a pressing need for large,
      prospective studies of the frequency and clinical course of AVMs in well-defined,
      stable populations, taking account of their prognostic heterogeneity.

PMID- 11571211
TI  - Gene expression profiling of the nervous system in murine experimental autoimmune
      encephalomyelitis.
AB  - Multiple sclerosis is thought to be a polygenic disease driven by dysregulation
      of the immune system leading to an autoimmune response against one or several
      antigens of cerebral white matter tissue. Experimental autoimmune
      encephalomyelitis (EAE) is a mouse model that is used to study the aetiology and
      pathogenesis of multiple sclerosis and new therapeutic approaches. We used
      oligonucleotide microarrays to determine gene expression profiles of the inflamed
      spinal cords of EAE mice at the onset and at the peak of the disease. Of the
      approximately 11 000 genes studied, 213 were regulated differentially and 100
      showed consistent differential regulation throughout the disease. Inflammation
      resulted in a profile of increased gene expression of immune-related molecules,
      extracellular matrix and cell adhesion molecules and molecules involved in cell
      division and transcription, and differential regulation of molecules involved in
      signal transduction, protein synthesis and metabolism. Of the 104 genes with
      defined chromosomal locations, 51 mapped to known EAE-linked quantitative trait
      loci and as such are putative candidate genes for susceptibility to EAE.

PMID- 11571212
TI  - CAG repeat expansion in the TATA box-binding protein gene causes autosomal
      dominant cerebellar ataxia.
AB  - At least 13 loci responsible for autosomal dominant cerebellar ataxia (ADCA) have
      been identified. Spinocerebellar ataxia 1, 2, 3, 6 and 7 are caused by translated
      CAG repeat expansions. However, in France, >30% of ADCAs are not explained by the
      known genes. Recently, analysis of the TATA box-binding protein (TBP) gene, one
      of the transcription factors known to contain a CAG/CAA repeat, in patients with
      progressive cerebellar ataxia revealed one sporadic case with 63 repeats. We
      examined this gene in 162 index cases with ADCA. An expanded repeat with 46
      repeat units was detected in a single index case from Belgium. In this family,
      two affected members and six unaffected, but at-risk, individuals carried
      expanded alleles. Interestingly, the expanded repeat was stable during
      transmission. The main clinical features in six patients were cerebellar ataxia,
      dementia and behavioural disturbances with onset in their fourth to sixth decade.
      The main neuropathological finding was severe neuronal loss and gliosis in the
      Purkinje cell layer. Immunohistochemical analysis showed neuronal intranuclear
      inclusions containing expanded polyglutamine, indicating that this disease shares
      several features with other polyglutamine diseases. This study demonstrates that
      CAG/CAA repeat expansion in the TBP gene causes ADCA with dementia and/or
      psychiatric manifestations.

PMID- 11571213
TI  - Familial frontotemporal dementia with ubiquitin-positive inclusions is linked to
      chromosome 17q21-22.
AB  - Hereditary frontotemporal dementia (FTD) is an autosomal dominant
      neurodegenerative disorder that is associated with mutations in the tau gene and
      with the pathological accumulation of hyperphosphorylated tau protein in affected
      brain cells in about a quarter of cases. However, most FTD families have no
      demonstrable tau mutations. Here we describe the clinical and neuropathological
      features of a large family with hereditary FTD. Genetic analysis showed strong
      evidence for linkage to chromosome 17q21-22 (maximum lod score 3.46, theta = 0
      for marker D17S950), but mutations in the tau gene were not found. Clinical
      symptoms, neuropsychological deficits and neuroimaging findings of affected
      family members were similar to sporadic and tau-related FTD. The mean age at
      onset was 61.2 years, with loss of initiative and decreased spontaneous speech as
      the most prominent presenting symptoms. Pathological examination of the brains of
      two affected family members showed non-specific neuronal degeneration with dense
      cytoplasmic ubiquitin-positive inclusions in neurones of the second layer of the
      frontotemporal cortex and dentate gyrus of the hippocampus. In a number of
      neurones these inclusions appeared to be located inside the nucleus, although due
      to the small number of these inclusions this localization could not be confirmed
      by electron microscopy. The inclusions were not stained by tau, alpha-synuclein
      or polyglutamine antibodies. Biochemical analysis of soluble tau did not reveal
      abnormalities in tau isoform distribution and analysis of mRNA showed the
      presence of both three- and four-repeat transcripts. This is the first report of
      ubiquitin-positive, tau-negative inclusions in an FTD family with significant
      linkage to chromosome 17q21-22. Further characterization of the ubiquitin
      positive inclusions may clarify the neurodegenerative pathways involved in this
      subtype of FTD.

PMID- 11571214
TI  - Clinical, electrophysiological and molecular genetic characteristics of 93
      patients with X-linked Charcot-Marie-Tooth disease.
AB  - X-linked dominant Charcot-Marie-Tooth (CMTX) disease is a motor and sensory
      neuropathy caused by mutations in the connexin 32 (CX32) gene. In this study we
      report the clinical, electrophysiological and genetic features of 93 patients (41
      males, 52 females) from 37 unrelated families with CMTX. Age at onset was 15.4 +/
      9.6 years in males (range 1-40 years) and 18.7 +/- 13.1 years in females (range
      1-56 years) (P = 0.22) and the duration of disease at the time of examination was
      18.3 +/- 14.6 years in males and 23.9 +/- 13.7 years in females (P = 0.11). Males
      were more severely affected than females, with significantly more frequent muscle
      weakness, amyotrophy, proprioception loss, upper limb areflexia and pes cavus.
      Females were more frequently asymptomatic, whereas high functional disability
      scores were more frequently encountered in males. The electrophysiological
      studies showed that motor nerve conduction velocities in CMTX females, but not
      males, were heterogeneous between nerves compared with Charcot-Marie-Tooth type
      1A (CMT1A) patients and controls. The terminal latency index (TLI) for the median
      nerve was 0.37 +/- 0.08; it was similar in men and in women and a little higher
      than those observed in CMT1A and controls. The range of values for median TLI was
      wider in both male and female CMTX patients than in controls, but was similar to
      that of CMT1A patients, suggesting that motor conduction was relatively
      homogeneous within a given nerve. Twenty-seven different CX32 mutations,
      including missense (n = 23), nonsense (n = 2) and frameshift mutations (n = 1)
      and one entire deletion of the CX32 coding sequence, were observed in the 37
      families. Four of these mutations are described for the first time. The phenotype
      of the patients, especially age at onset, is discussed in relation to the
      functional consequences of CX32 mutations, analysed in vitro in Xenopus oocytes
      and mammalian cells. CMTX patients with age at onset in the first decade mostly
      presented non-functional mutations, suggesting that the physiological
      consequences of the mutations affect age at onset in CMTX.

PMID- 11571215
TI  - The clinical and laboratory features of chronic sensory ataxic neuropathy with
      anti-disialosyl IgM antibodies.
AB  - The clinical and laboratory phenotype of a paraproteinaemic neuropathy syndrome
      termed chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies is
      described in a series of 18 cases. Previous single case reports have outlined
      some features of this syndrome. All 18 cases were defined by the presence of
      serum IgM antibodies which react principally with NeuAc (alpha2-8)NeuAc(alpha2
      3)Gal-configured disialosyl epitopes common to many gangliosides including GDlb,
      GD3, GTlb and GQlb. In 17 out of 18 cases, the serum contained benign IgM
      paraproteins, and in four of these cases at least two IgM paraproteins were
      present. The IgM antibodies were also cold agglutinins in 50% of cases. The
      clinical picture comprised a chronic neuropathy with marked sensory ataxia and
      areflexia, and with relatively preserved motor function in the limbs. In
      addition, 16 out of 18 cases had motor weakness affecting oculomotor and bulbar
      muscles as fixed or as relapsing-remitting features. When present in their
      entirety, these clinical features have been described previously under the
      acronym CANOMAD: chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein,
      cold agglutinins and disialosyl antibodies. This distribution of clinical
      features is reminiscent of Miller Fisher syndrome, in which acute-phase anti
      disialylated ganglioside IgG antibodies are found. Clinical electrophysiology and
      nerve biopsy show both demyelinating and axonal features. A partial response to
      intravenous immunoglobulin and other treatments is reported in some cases.

PMID- 11571216
TI  - Plasminogen activators in multiple sclerosis lesions: implications for the
      inflammatory response and axonal damage.
AB  - Components of the plasminogen activator (PA) and matrix metalloprotease (MMP)
      cascade have been characterized in multiple sclerosis lesions by
      immunohistochemistry, enzyme-linked immunosorbent assay and enzyme activity
      assays in order to establish a functional role for the enzyme sequence in lesion
      development. Highly significant quantitative increases in urokinase PA (uPA),
      urokinase receptor (uPAR) and plasminogen activator inhibitor-1 were detected in
      acute multiple sclerosis lesions (P < 0.0001) and in uPAR in normal-appearing
      white matter (P < 0.0001) compared with control tissue. All three proteins were
      immunolocalized to mononuclear cells in perivascular cuffs and to macrophages in
      the lesion parenchyma. MMP-9 and the tissue inhibitor of metalloprotease-1 also
      increased during lesion development but the enzyme was present largely in the
      inactive pro-form. In contrast to uPA, the concentration and activity of tissue
      PA (tPA), the most abundant plasminogen activator in normal control brain, were
      reduced in multiple sclerosis specimens. In acute lesions tPA co-localized with
      fibrin(ogen) on large diameter axons also stained with SMI-32, an
      immunohistochemical marker of axonal damage. The uPA-uPAR complex, concentrated
      on inflammatory cells in the perivascular zone of the evolving lesion, may
      facilitate cellular infiltration into the CNS which is amplified by MMP- mediated
      degradation of blood vessel matrix. tPA localization on injured axons may be a
      marker of axonal damage or represent a protective mechanism aimed at removal of
      fibrin deposits and restoration of axonal function.

PMID- 11571217
TI  - Does primary lateral sclerosis exist? A study of 20 patients and a review of the
      literature.
AB  - The question of whether primary lateral sclerosis (PLS) is a nosological entity
      distinct from amyotrophic lateral sclerosis (ALS) has been the subject of
      controversy since it was first described in the nineteenth century. PLS has been
      defined as a rare, non-hereditary disease characterized by progressive
      spinobulbar spasticity, related to the selective loss of precentral pyramidal
      neurones, with secondary pyramidal tract degeneration and preservation of
      anterior horn motor neurones. In the recent clinical literature, the frontier
      between ALS and neurodegenerative disease remains poorly defined. We studied 20
      patients with a diagnosis of PLS. We carried out a variety of tests in order to
      determine the presence of a more diffuse neurodegenerative process. We also
      performed a longitudinal electrophysiological evaluation. Our clinical,
      electrophysiological and pathological investigations provide evidence that the
      disease has a heterogeneous clinical presentation and that degeneration is not
      restricted to the central motor system.

PMID- 11571218
TI  - Respiratory muscle strength and ventilatory failure in amyotrophic lateral
      sclerosis.
AB  - Although ventilatory failure is the most common cause of death in amyotrophic
      lateral sclerosis (ALS) and measurement of respiratory muscle strength (RMS) has
      been shown to have prognostic value, no single test of strength can predict the
      presence of hypercapnia reliably. RMS was measured in 81 ALS patients to evaluate
      the relationship between tests of RMS and the presence of ventilatory failure,
      defined as a carbon dioxide tension > or = 6 kPa. We studied the predictive value
      of vital capacity (VC), static inspiratory and expiratory mouth pressures (MIP,
      MEP), maximal sniff oesophageal (sniff P(oes)), transdiaphragmatic (sniff P(di))
      and nasal (SNP) pressure, cough gastric (cough P(gas)) pressure and
      transdiaphragmatic pressure after bilateral cervical magnetic phrenic nerve
      stimulation (CMS P(di)) to identify the risk of ventilatory failure in the whole
      group and in subgroups of patients with and without significant bulbar
      involvement. For patients without significant bulbar involvement, sniff P(di) had
      greatest predictive power [odds ratio (OR) 57] with specificity, sensitivity and
      positive and negative predictive values (PPV, NPV) of 87, 90, 74 and 95%,
      respectively Of the less invasive tests, per cent predicted SNP had greater
      overall predictive power (OR 25, specificity 85%, sensitivity 81%) than per cent
      predicted VC (9, 89%, 53%) and per cent predicted MIP (6, 83%, 55%). No test had
      significant predictive power for the presence of hypercapnia when used to measure
      RMS in a subgroup of patients with significant bulbar weakness. Thirty-five
      patients underwent polysomnography. CMS P(di), sniff P(di) and per cent predicted
      SNP were significantly correlated with the apnoea/hypopnoea index (AHI) (P =
      0.035, 0.042 and 0.026, respectively). The correlations between AHI and per cent
      predicted MIP and VC were less strong (both non-significant). In ALS patients
      without significant bulbar involvement, novel tests of RMS have greater
      predictive power than conventional tests to predict hypercapnia. In particular,
      the non-invasive SNP is more sensitive than VC and MIP, suggesting that it could
      usefully be included in tests of respiratory muscle strength in ALS and will be
      helpful in assessing the risk of ventilatory failure. In patients with
      significant bulbar involvement, tests of respiratory muscle strength do not
      predict hypercapnia. Sleep-disordered breathing is correlated with RMS and the
      novel tests of RMS having the strongest relationship with the degree of sleep
      disturbance.

PMID- 11571220
TI  - The neural organization of discourse: an H2 15O-PET study of narrative production
      in English and American sign language.
AB  - In order to identify brain regions that play an essential role in the production
      of discourse, H2 15O-PET scans were acquired during spontaneous generation of
      autobiographical narratives in English and in American Sign Language in hearing
      subjects who were native users of both. We compared languages that differ
      maximally in their mode of expression yet share the same core linguistic
      properties in order to differentiate the stages of discourse production:
      differences between the languages should reflect later, modality-dependent stages
      of phonological encoding and articulation; congruencies are more likely to reveal
      the anatomy of earlier modality-independent stages of conceptualization and
      lexical access. Common activations were detected in a widespread array of
      regions; left hemisphere language areas classically related to speech were also
      robustly activated during sign production, but the common neural architecture
      extended beyond the classical language areas and included extrasylvian regions in
      both right and left hemispheres. Furthermore, posterior perisylvian and basal
      temporal regions appear to play an integral role in spontaneous self-generated
      formulation and production of language, even in the absence of exteroceptive
      stimuli. Results additionally indicate that anterior and posterior areas may play
      distinct roles in early and late stages of language production, and suggest a
      novel model for lateralization of cerebral activity during the generation of
      discourse: progression from the early stages of lexical access to later stages of
      articulatory-motor encoding may constitute a progression from bilateral to left
      lateralized activation. This pattern is not predicted by the standard Wernicke
      Geschwind model, and may become apparent when language is produced in an
      ecologically valid context.

PMID- 11571219
TI  - In vivo visualization of activated glia by [11C] (R)-PK11195-PET following herpes
      encephalitis reveals projected neuronal damage beyond the primary focal lesion.
AB  - A major challenge in the assessment of brain injury and its relationship to the
      ensuing functional deficits is the accurate delineation of the areas of damage.
      Here, we test the hypothesis that the anatomical distribution pattern of
      activated microglia, a normally dormant population of resident brain macrophages,
      can be used as a surrogate marker of neuronal injury not only at the primary
      lesion site but also in the antero- and retrograde projection areas of the
      lesioned neurones. Two patients with asymmetrical herpes simplex encephalitis
      were serially scanned 6 and 12 months after the acute illness using PET with
      [11C] (R)-PK11195, a marker of activated microglia/brain macrophages. The
      evolving structural changes in the brain were measured by volumetric MRI and
      compared with the pattern of [11C](R)-PK11195 binding. Corresponding to the
      clinically observed cognitive deficits, quantitative [11C](R)-PK11195-PET
      revealed highly significant signal increases within the affected limbic system
      and additionally in areas connected to the limbic system by neural pathways,
      including the lingual gyrus in the occipital lobe and the inferior parietal lobe,
      which had normal morphology on structural MRI. The increased [11C](R)-PK11195
      binding, signifying the presence of activated microglia, persisted many months
      (>12) after antiviral treatment. Cortical areas that showed early high [11C](R)
      PK11195 binding subsequently underwent atrophy. These observations demonstrate
      that in vivo imaging of activated microglia/brain macrophages provides a dynamic
      measure of active tissue changes following an acute focal lesion. Importantly,
      the glial tissue response in the wake of neuronal damage is protracted and
      widespread within the confines of the affected distributed neural system and can
      be related to the long-term functional deficits.

PMID- 11571221
TI  - Control of volitional and reflexive saccades in Tourette's syndrome.
AB  - Tourette's syndrome is characterized by involuntary tics and, although the
      underlying pathogenesis and pathophysiology of Tourette's syndrome remains
      unclear, it is suspected that basal ganglia structures are involved. The basal
      ganglia also play an important role in the control of saccadic eye movements and
      we therefore hypothesize that Tourette's syndrome patients have abnormal control
      of saccadic eye movements. In this study, 10 subjects with Tourette's syndrome
      and 10 age- and sex-matched controls performed four different oculomotor
      paradigms requiring the execution and/or suppression of reflexive and/or
      voluntary saccades. In the immediate saccade tasks, subjects were required to
      look either toward (pro-saccade task) or away from (anti-saccade task) a
      peripheral target as soon as it appeared. In the delayed saccade tasks, subjects
      were instructed to wait for a central fixation point to disappear before
      initiating eye movements. Among Tourette's syndrome subjects, saccadic reaction
      times were longer in all tasks. Saccadic amplitudes were smaller in Tourette's
      syndrome subjects, and they made more saccades to reach the eccentric target. The
      occurrence of direction errors (i.e. reflexive pro-saccades on anti-saccade
      trials) was normal in the immediate anti-saccade task, suggesting that the
      ability to inhibit reflexive saccades towards novel stimuli was not impaired in
      Tourette's syndrome. Timing errors (i.e. eye movements made prior to
      disappearance of the central fixation point in delayed saccade tasks) were
      significantly greater among Tourette's syndrome subjects. Moreover, these errors
      were predominantly made towards the first target of the remembered sequence in a
      delayed memory-guided sequential saccade task. These results indicate that the
      ability to inhibit or delay planned motor programmes is significantly impaired in
      Tourette's syndrome. We hypothesize that altered cortical-basal ganglia circuitry
      leads to reduced cortical inhibition making it harder for Tourette's syndrome
      subjects to withhold the execution of planned motor programmes.

PMID- 11571222
TI  - Face processing occurs outside the fusiform 'face area' in autism: evidence from
      functional MRI.
AB  - Processing the human face is at the focal point of most social interactions, yet
      this simple perceptual task is difficult for individuals with autism, a
      population that spends limited amounts of time engaged in face-to-face eye
      contact or social interactions in general. Thus, the study of face processing in
      autism is not only important because it may be integral to understanding the
      social deficits of this disorder, but also, because it provides a unique
      opportunity to study experiential factors related to the functional
      specialization of normal face processing. In short, autism may be one of the only
      disorders where affected individuals spend reduced amounts of time engaged in
      face processing from birth. Using functional MRI, haemodynamic responses during a
      face perception task were compared between adults with autism and normal control
      subjects. Four regions of interest (ROIs), the fusiform gyrus (FG), inferior
      temporal gyrus, middle temporal gyrus and amygdala were manually traced on non
      spatially normalized images and the percentage ROI active was calculated for each
      subject. Analyses in Talairach space were also performed. Overall results
      revealed either abnormally weak or no activation in FG in autistic patients, as
      well as significantly reduced activation in the inferior occipital gyrus,
      superior temporal sulcus and amygdala. Anatomical abnormalities, in contrast,
      were present only in the amygdala in autistic patients, whose mean volume was
      significantly reduced as compared with normals. Reaction time and accuracy
      measures were not different between groups. Thus, while autistic subjects could
      perform the face perception task, none of the regions supporting face processing
      in normals were found to be significantly active in the autistic subjects.
      Instead, in every autistic patient, faces maximally activated aberrant and
      individual-specific neural sites (e.g. frontal cortex, primary visual cortex,
      etc.), which was in contrast to the 100% consistency of maximal activation within
      the traditional fusiform face area (FFA) for every normal subject. It appears
      that, as compared with normal individuals, autistic individuals 'see' faces
      utilizing different neural systems, with each patient doing so via a unique
      neural circuitry. Such a pattern of individual-specific, scattered activation
      seen in autistic patients in contrast to the highly consistent FG activation seen
      in normals, suggests that experiential factors do indeed play a role in the
      normal development of the FFA.

PMID- 11571223
TI  - Prefrontal regions involved in keeping information in and out of mind.
AB  - Goal-directed behaviour depends on keeping relevant information in mind (working
      memory) and irrelevant information out of mind (behavioural inhibition or
      interference resolution). Prefrontal cortex is essential for working memory and
      for interference resolution, but it is unknown whether these two mental abilities
      are mediated by common or distinct prefrontal regions. To address this question,
      functional MRI was used to identify brain regions activated by separate
      manipulations of working memory load and interference within a single task (the
      Sternberg item recognition paradigm). Both load and interference manipulations
      were associated with performance decrements. Subjects were unaware of the
      interference manipulation. There was a high degree of overlap between the regions
      activated by load and interference, which included bilateral ventrolateral and
      dorsolateral prefrontal cortex, anterior insula, anterior cingulate and parietal
      cortex. Critically, no region was activated exclusively by interference. Several
      regions within this common network exhibited a brain-behaviour correlation across
      subjects for the load or interference manipulation. Activation within the right
      middle frontal gyrus and left inferior frontal gyrus was correlated with the
      ability to resolve interference efficiently, but not the ability to manage an
      increased working memory load efficiently. Conversely, activation of the anterior
      cingulate was correlated with load susceptibility, but was not correlated with
      interference susceptibility. These findings suggest that, within the circuitry
      engaged by this task, some regions are more critically involved in the resolution
      of interference whereas others are more involved in the resolution of an increase
      in load. The anterior cingulate was engaged to a greater extent by the load than
      interference manipulation, suggesting that this region, which is thought to be
      involved in detecting the need for greater allocation of attentional resources,
      may be particularly implicated during awareness of the need for cognitive
      control. In the present study, interference resolution did not involve
      recruitment of additional inhibitory circuitry, but was instead mediated by a
      subset of the neural system supporting working memory.

PMID- 11571224
TI  - Identification of famous faces and buildings: a functional neuroimaging study of
      semantically unique items.
AB  - Several functional imaging experiments have clearly established that the fusiform
      gyri are preferentially responsive to faces, whereas the parahippocampal/lingual
      gyri are more responsive to buildings. Other studies have demonstrated that
      famous faces additionally activate the anterior temporal cortex relative to
      unfamiliar faces, animals, tools, body parts and maps. One explanation for this
      apparent specialization for known people could be that famous faces are
      'semantically unique items'. In other words, they carry unique semantic
      associations that are not shared by other perceptually similar category members.
      If this hypothesis is correct, the anterior temporal cortex should also respond
      to other semantically unique items, such as famous buildings. In this PET study,
      we investigated the effect of fame (famous relative to non-famous) on activation
      elicited by famous and non-famous faces and buildings during a same-different
      matching task. We found that, when the task was held constant, category-specific
      activations in the fusiform and parahippocampal/lingual areas were not modulated
      by fame. In contrast, in the left anterior middle temporal gyrus there was an
      effect of fame that was common to faces and buildings. These results suggest that
      the identification of famous faces and buildings involves category-specific
      perceptual processing in the fusiform and parahippocampal/lingual regions,
      respectively, and shared analysis of unique semantic attributes in the left
      anterior temporal cortex.

PMID- 11571225
TI  - Pain and the body schema: evidence for peripheral effects on mental
      representations of movement.
AB  - Some accounts of body representations postulate a real-time representation of the
      body in space generated by proprioceptive, somatosensory, vestibular and other
      sensory inputs; this representation has often been termed the 'body schema'. To
      examine whether the body schema is influenced by peripheral factors such as pain,
      we asked patients with chronic unilateral arm pain to determine the laterality of
      pictured hands presented at different orientations. Previous chronometric
      findings suggest that performance on this task depends on the body schema, in
      that it appears to involve mentally rotating one's hand from its current position
      until it is aligned with the stimulus hand. We found that, as in previous
      investigations, participants' response times (RTs) reflected the degree of
      simulated movement as well as biomechanical constraints of the arm. Importantly,
      a significant interaction between the magnitude of mental rotation and limb was
      observed: RTs were longer for the painful arm than for the unaffected arm for
      large-amplitude imagined movements; controls exhibited symmetrical RTs. These
      findings suggest that the body schema is influenced by pain and that this task
      may provide an objective measure of pain.

PMID- 11571226
TI  - Lidocaine and muscimol microinjections in subthalamic nucleus reverse
      Parkinsonian symptoms.
AB  - Inactivation of neurones in the subthalamic nucleus (STN) of the 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine treated monkey model of Parkinson's disease has
      been shown to relieve parkinsonian motor symptoms. In patients with Parkinson's
      disease, neurones in the STN display hyperactive firing rates and rhythmic
      discharge activity such as tremor-related oscillations (3-8 Hz) and synchronous
      high-frequency oscillations (15-30 Hz). In this study, microinjections of
      lidocaine (n = 4) and muscimol, a GABA(A) receptor agonist (n = 2), were
      performed in the STN of six patients with Parkinson's disease to determine
      whether the focal suppression of STN neuronal activity can lead to an improvement
      in tremor, bradykinesia and rigidity. We also report the first use of
      microelectrode recording of the effects of microinjections on neuronal activity
      in the human brain (n = 2). Microinjections of 10-23 microl of lidocaine produced
      striking improvements in bradykinesia, limb tremor and rigidity in three out of
      three patients. These improvements were correlated with good therapeutic effects
      of subsequent STN deep brain stimulation performed in the same microelectrode
      trajectories as these injections. The most dramatic observation following
      lidocaine injections was the appearance of dyskinetic limb movements. In one
      patient, simultaneous microelectrode recording during an injection of 3.5 microl
      of lidocaine demonstrated a suppression of neuronal activity at distances of <
      0.9 mm from the injection site, but no suppression was observed at > or = 1.2 mm
      from the injection site. Microinjections of 5-10 microl of muscimol in a region
      with tremor-related activity resulted in suppression of limb tremor in two out of
      two patients. Interestingly, in one of these patients, 4 Hz oscillatory activity
      was diminished in a neurone recorded 1.3 mm from the injection site, but there
      was no reduction in the mean firing rate or 20 Hz oscillatory activity. These
      results demonstrate that inactivation of neuronal activity in the STN of patients
      with Parkinson's disease improves motor symptoms. These findings also suggest
      that a focal block of the STN might alter the oscillatory activity of neurones
      located beyond the inhibited region.

PMID- 11571227
TI  - Molecular pathogenesis of the von Hippel-Lindau hereditary cancer syndrome:
      implications for oxygen sensing.

PMID- 11571228
TI  - The Smad transcriptional corepressor TGIF recruits mSin3.
AB  - The homeodomain protein TG-interacting factor (TGIF) represses transcription by
      histone deacetylase-dependent and -independent means. Heterozygous mutations in
      human TGIF result in holoprosencephaly, a severe genetic disorder affecting
      craniofacial development, suggesting that TGIF is critical for normal
      development. After transforming growth factorbeta (TGFbeta) stimulation, Smad
      proteins enter the nucleus and form transcriptional activation complexes or
      interact with TGIF, which functions as a corepressor. The relative levels of Smad
      corepressors and coactivators present within the cell may determine the outcome
      of a TGFbeta response. We show that TGIF interacts directly with the paired
      amphipathic alpha-helix 2 domain of the mSin3 corepressor, and TGIF recruits
      mSin3 to a TGFbeta-activated Smad complex. The mSin3 interaction domain of TGIF
      has been shown to be essential for repression of a TGFbeta transcriptional
      response. Thus, TGIF represents a targeting component of the mSin3 corepressor
      complex.

PMID- 11571229
TI  - Targeting of protein kinase C delta to mitochondria in the oxidative stress
      response.
AB  - The cellular response to oxidative stress includes the release of mitochondrial
      cytochrome c and the induction of apoptosis. Here we show that treatment of
      diverse cells with hydrogen peroxide (H2O2) induces the targeting of protein
      kinase C delta (PKCdelta) to mitochondria. The results demonstrate that H2O2
      induced activation of PKCdelta is necessary for translocation of PKCdelta from
      the cytoplasm to the mitochondria. The results also show that mitochondrial
      targeting of PKCdelta is associated with the loss of mitochondrial transmembrane
      potential and release of cytochrome c. The functional importance of this event is
      also supported by the demonstration that H2O2-induced apoptosis is blocked by the
      inhibition of PKCdelta activation and translocation to mitochondria. These
      findings indicate that mitochondrial targeting of PKCdelta is required, at least
      in part, for the apoptotic response of cells to oxidative stress.

PMID- 11571230
TI  - RRR-alpha-tocopheryl succinate induces MDA-MB-435 and MCF-7 human breast cancer
      cells to undergo differentiation.
AB  - RRR-alpha-Tocopheryl succinate (vitamin E succinate, VES) is a potent antitumor
      agent, inducing DNA synthesis arrest, differentiation, and apoptosis. Because
      little is known about VES-induced differentiation, studies reported here
      characterize VES effects on the differentiation status of human breast cancer
      cell lines and investigate possible molecular mechanisms involved. VES-induced
      differentiation of human MCF-7 and MDA-MB-435 breast cancer cells was
      characterized by morphological changes, induction of lipid droplets, induction of
      beta-casein mRNA expression, and down-regulation of Her2/neu protein. In
      contrast, VES treatment of normal human mammary epithelial cells, MCF-10A cells,
      and T-47D cells did not induce differentiation. Studies addressing mechanisms
      showed that neither antibody neutralization of the transforming growth factor
      beta signaling pathway nor expression of a dominant-negative mutant of c-Jun N
      terminal kinase blocked the ability of VES to induce differentiation; however,
      treatment of cells with PD 98059, a chemical inhibitor of mitogen-activated
      protein kinase kinase (MEK1/2), blocked the ability of VES to induce
      differentiation.

PMID- 11571231
TI  - Involvement of p38 kinase in hydroxyurea-induced differentiation of K562 cells.
AB  - Hydroxyurea is a differentiation-inducing agent of human erythroleukemia K562
      cells. However, the cellular mechanisms by which hydroxyurea exerts its effects
      on tumor cells, leading to the inhibition of cell growth and the induction of
      differentiation markers, are largely unknown. This study examined the role of
      different mitogen-activated protein kinase signal transduction pathways in
      hydroxyurea-induced erythroid differentiation of K562 cells. Using a panel of
      anti-extracellular signal-related kinase (ERK), c-Jun NH2-terminal kinase (JNK),
      and p38 phosphospecific antibodies, we demonstrated that phosphorylation of ERK
      and JNK is decreased after the treatment of cells with hydroxyurea, whereas
      phosphorylation of p38 is increased. Moreover, inhibition of ERK activity by
      PD98059 induced erythroid differentiation, and it acted synergistically with
      hydroxyurea on hemoglobin synthesis, whereas inhibition of p38 activity by
      SB203580 inhibited induction of hemoglobin production by hydroxyurea. These
      findings suggest that the activation of p38 kinase may play important roles in
      the signal transduction mechanisms of hydroxyurea leading to erythroid
      differentiation.

PMID- 11571232
TI  - Circulation impact factor is highest ever.

PMID- 11571233
TI  - Platelet collagen receptors and risk prediction in stroke and coronary artery
      disease.

PMID- 11571234
TI  - Cardiac biomarkers for rapid evaluation of chest pain.

PMID- 11571235
TI  - Revascularization versus implantable cardioverter-defibrillators to prevent
      sudden death in patients with severe left ventricular dysfunction.

PMID- 11571236
TI  - Novel platelet membrane glycoprotein VI dimorphism is a risk factor for
      myocardial infarction.
AB  - BACKGROUND: Glycoprotein (GP) VI plays a crucial role in platelet activation and
      aggregation. We investigated whether polymorphic variation at the GP VI locus
      confers an increased risk of myocardial infarction (MI). METHODS AND RESULTS:
      Coding and 5' and 3' non-coding regions of the GP VI gene were analyzed by
      polymerase chain reaction and conformation sensitive gel electrophoresis in 21
      healthy subjects. Ten dimorphisms, 5 of which predicted amino acid substitutions
      (T13254C, A19871G, A21908G, A22630T, C22644A), were identified. Two core
      haplotypes involving 7 dimorphisms (C10781A and G10873A and all those predicting
      amino acid substitutions) were apparent. The contribution of the T13254C
      dimorphism, which predicted the substitution of serine 219 by proline, to risk of
      MI was assessed in 525 patients with acute MI and 474 controls, all aged <75
      years. The allelic odds ratio (OR) for MI associated with the 13254C allele was
      1.16 (95% CI, 0.91 to 1.46; P=0.23). Compared with corresponding control
      subgroups, the 13254CC genotype was more common among cases who were female (OR,
      4.52; 95% CI, 1.23 to 16.64; P=0.029), nonsmokers (OR, 2.50; 95% CI, 0.98 to
      6.38; P=0.048), aged >/=60 years (OR, 6.48; 95% CI, 1.47 to 28.45; P=0.009) or
      carried the beta-fibrinogen -148T allele associated with increased fibrinogen
      levels (OR, 10.49; 95% CI, 1.32 to 83.42; P=0.02). In logistic regression
      analysis that took other cardiovascular risk factors into account, the
      interactions of GP VI genotype with age (P=0.005) and beta-fibrinogen genotype
      (P=0.035) remained significant. CONCLUSIONS: The GP VI 13254CC genotype increases
      the risk of MI, particularly in older individuals, and the interaction of the GP
      VI 13254C allele with other candidate risk alleles may accentuate this risk.

PMID- 11571237
TI  - Improved arterial compliance by a novel advanced glycation end-product crosslink
      breaker.
AB  - BACKGROUND: Arterial stiffening with increased pulse pressure is a leading risk
      factor for cardiovascular disease in the elderly. We tested whether ALT-711, a
      novel nonenzymatic breaker of advanced glycation end-product crosslinks,
      selectively improves arterial compliance and lowers pulse pressure in older
      individuals with vascular stiffening. METHODS AND RESULTS: Nine US centers
      recruited and randomly assigned subjects with resting arterial pulse pressures
      >60 mm Hg and systolic pressures >140 mm Hg to once-daily ALT-711 (210 mg; n=62)
      or placebo (n=31) for 56 days. Preexisting antihypertensive treatment (90% of
      subjects) was continued during the study. Morning upright blood pressure, stroke
      volume, cardiac output, systemic vascular resistance, total arterial compliance,
      carotid-femoral pulse wave velocity, and drug tolerability were assessed. ALT-711
      netted a greater decline in pulse pressures than placebo (-5.3 versus -0.6 mm Hg
      at day 56; P=0.034 for treatment effect by repeated-measures ANOVA). Systolic
      pressure declined in both groups, but diastolic pressure fell less with ALT-711
      (P=0.056). Mean pressure declined similarly in both groups (-4 mm Hg; P<0.01 for
      each group, P=0.34 for treatment effect). Total arterial compliance rose 15% in
      ALT-711-treated subjects versus no change with placebo (P=0.015 versus ALT-711),
      an effect that did not depend on reduced mean pressure. Pulse wave velocity
      declined 8% with ALT-711 (P<0.05 at day 56, P=0.08 for treatment effect).
      Systemic arterial resistance, cardiac output, and heart rate did not
      significantly change in either group. CONCLUSIONS: ALT-711 improves total
      arterial compliance in aged humans with vascular stiffening, and it may provide a
      novel therapeutic approach for this abnormality, which occurs with aging,
      diabetes, and isolated systolic hypertension.

PMID- 11571238
TI  - Unstable angina and elevated c-reactive protein levels predict enhanced
      vasoreactivity of the culprit lesion.
AB  - BACKGROUND: Because plaque inflammation may modulate coronary vasomotion, the
      association between systemic levels of C-reactive protein (CRP) and coronary
      vasoreactivity was assessed in patients with stable or unstable angina. METHODS
      AND RESULTS: In 31 patients with stable angina and 23 patients with unstable
      angina undergoing coronary angiography, minimal luminal diameter (MLD) of the
      culprit lesion was measured by quantitative coronary angiography at baseline,
      during the cold pressor test (CPT), and after intracoronary administration of
      nitroglycerin (NTG) and expressed as percent change from baseline. MLD of
      patients with unstable angina exhibited a greater reduction during CPT and a
      greater increase after NTG than did patients with stable angina (-17+/-14% versus
      -5+/-12%, P=0.0013, and 34+/-25% versus 8+/-20%, P<0.001, respectively).
      According to preprocedural serum levels of CRP, 36 patients had normal (</=0.5
      mg/dL) and 18 patients had elevated CRP levels. MLD of patients with elevated CRP
      levels exhibited a greater reduction during CPT and a greater increase after NTG
      than of patients with normal CRP levels (-15+/-12% versus -7+/-14%, P=0.037, and
      31+/-23% versus 13+/-25%, P=0.011, respectively). Both unstable angina and
      elevated CRP levels resulted in independent predictors of enhanced vasoreactivity
      at the multivariate analysis. CONCLUSIONS: This study confirms enhanced
      vasoreactivity of the culprit lesion in patients with unstable angina compared
      with those with stable angina. More importantly, it demonstrates that
      inflammatory mechanisms play a key role in modulating the reactivity of coronary
      atherosclerotic plaques and may partially account for the enhanced vasoreactivity
      of the unstable plaques.

PMID- 11571239
TI  - Left ventricular muscle mass and elevated heart rate are associated with coronary
      plaque disruption.
AB  - BACKGROUND: Plaque disruption is the central pathophysiological mechanism
      underlying acute coronary syndromes and the progression of coronary
      atherosclerosis. There exists only scant information about the factors that are
      associated with its development. The aim of the current study was to analyze the
      contribution of hemodynamic forces in the pathogenesis of plaque disruption.
      Plaque disruption was diagnosed by coronary angiography of stenosed but not
      completely occluded coronary arteries. METHODS AND RESULTS: This study
      retrospectively analyzed 106 patients who underwent 2 coronary angiography
      procedures within 6 months. We investigated 53 patients with initially smooth
      stenoses who developed plaque disruption by the time of the second coronary
      angiogram and compared these patients with 53 age- and sex-matched individuals
      with smooth stenoses without angiographic signs of plaque disruption. The 2
      groups were compared by analyzing central hemodynamics, echocardiographic
      measurements, and cardiovascular medication use. Logistic regression analysis
      identified positive associations between plaque disruption, left ventricular
      muscle mass >270 g, and a mean heart rate >80 bpm and a negative association with
      the use of beta-blockers. CONCLUSIONS: The associations documented by our
      investigation indicate that hemodynamic forces may play a crucial role in the
      pathogenesis of plaque disruption. These findings may help to identify patients
      who are at an increased risk of plaque disruption and who might gain benefit from
      pharmacological interventions aimed at reducing heart rate, for example, by the
      use of beta-blockers, or a reduction of left ventricular hypertrophy.

PMID- 11571240
TI  - Ninety-minute exclusion of acute myocardial infarction by use of quantitative
      point-of-care testing of myoglobin and troponin I.
AB  - BACKGROUND: Diagnostic strategies with ECG and serum cardiac markers have been
      used to rule out acute myocardial infarction in 6 to 12 hours. The present study
      evaluated whether a multimarker strategy that used point-of-care measurement of
      myoglobin, creatine kinase (CK)-MB, and troponin I could exclude acute myocardial
      infarction in </=3 hours. METHODS AND RESULTS: We prospectively enrolled
      consecutive patients (n=817) in the emergency department who were evaluated for
      possible acute myocardial infarction. In patients with nondiagnostic ECGs, we
      measured CK-MB, troponin I, and myoglobin with a point-of-care device at
      presentation and at 90 minutes, 3 hours, and 9 hours. Standard central laboratory
      testing of CK-MB was done at the same time intervals, and triage decisions were
      made by emergency physicians who were unaware of point-of-care results.
      Sensitivity and negative predictive value were compared for both the multimarker,
      point-of-care approach and the central laboratory strategy. Sensitivity and
      negative predictive value for point-of-care combination of myoglobin and troponin
      I by 90 minutes was 96.9% and 99.6%, respectively. CK-MB measurements and blood
      sampling at 3 hours did not improve sensitivity or negative predictive value.
      Median time from sampling to reporting of results was 71.0 minutes for the
      central laboratory versus 24.0 minutes for the point-of-care device (P<0.001).
      CONCLUSIONS: Acute myocardial infarction can be excluded rapidly in the emergency
      department by use of point-of-care measurements of myoglobin and troponin I
      during the first 90 minutes after presentation.

PMID- 11571241
TI  - Prior coronary artery bypass surgery and risk of death among patients with
      ischemic left ventricular dysfunction.
AB  - BACKGROUND: Patients with ischemic LV dysfunction are at high risk of sudden
      death. However, no benefit from prophylactic defibrillator therapy was observed
      in a group of patients with LV dysfunction undergoing CABG (CABG Patch trial).
      Thus, the effect of CABG on future risk of sudden death in patients with LV
      dysfunction is of considerable interest. METHODS AND RESULTS: Mortality and modes
      of death in 5410 patients with ischemic LV dysfunction who were enrolled in the
      Studies of Left Ventricular Dysfunction (SOLVD) trials were evaluated. Outcomes
      of patients with (n=1870, 35%) versus without (n=3540) history of prior CABG were
      compared, and stratification by baseline ejection fraction (EF) values (<0.25,
      0.25 to 0.30, and >0.30) was performed. Prior CABG was associated with a 25% (95%
      CI, 15% to 36%) reduction in risk of death and a 46% (95% CI, 30% to 58%)
      reduction in risk of sudden death independent of EF and severity of heart failure
      symptoms. As baseline EF declined, absolute reduction in risk of sudden death
      with prior CABG increased (P<0.01). No alteration in risk of death from
      progressive heart failure was observed with prior CABG. When these results were
      applied to a group of patients with LV dysfunction who had not undergone prior
      surgery (Coronary Artery Surgery Study Registry) predicted annual rates of death
      (8.2%) and sudden death (2.4%) were similar to those observed in the CABG Patch
      trial (7.9% and 2.3%, respectively). CONCLUSIONS: In patients with ischemic LV
      dysfunction, prior CABG is associated with a significant independent reduction in
      mortality. These results appear to account for the lack of benefit from
      defibrillator therapy in the CABG Patch trial.

PMID- 11571242
TI  - Complement activation in patients with congestive heart failure: effect of high
      dose intravenous immunoglobulin treatment.
AB  - BACKGROUND: Increasing evidence implicates innate immunity in the pathogenesis of
      congestive heart failure (CHF). In the present study, we examined the possible
      role of complement, an important part of innate immunity, in CHF. METHODS AND
      RESULTS: Complement activation was analyzed in systemic and coronary circulation
      in 39 patients with CHF and 20 healthy control subjects. In a double-blind,
      placebo-controlled study, we have recently reported that high-dose intravenous
      immunoglobulin (IVIG) improves left ventricular ejection fraction (LVEF) in these
      patients. To examine if this improvement was related to IVIG-induced effects on
      complement, we also examined complement activation during induction (first week)
      and maintenance therapy (6 months) with IVIG or placebo. Our main findings were:
      (1) We found enhanced systemic complement activation involving classic,
      alternative, as well as terminal pathway in patients with CHF compared with
      healthy control subjects. (2) Particularly enhanced complement activation was
      found in coronary sinus, representing venous drainage from the heart. (3) The
      systemic complement activation was further enhanced during IVIG but not during
      placebo therapy, particularly during induction therapy. (4) Although IVIG
      improved LVEF in patients with CHF, the degree of IVIG-mediated complement
      activation was negatively correlated with this improvement of LVEF. CONCLUSIONS:
      This study further supports the involvement of innate immunity in the
      pathogenesis of CHF. Our findings suggest that complement may be added to the
      list of possible therapeutic targets in CHF and that future studies with specific
      complement inhibitors may be of interest in this disorder.

PMID- 11571243
TI  - Effects of cavotricuspid isthmus ablation on atrioventricular node
      electrophysiology in patients with typical atrial flutter.
AB  - BACKGROUND: The atrial musculature in the cavotricuspid isthmus is a part of
      posterior inputs to the AV node. In patients with typical atrial flutter, effects
      of radiofrequency ablation of this isthmus on AV node conduction are still
      unknown. METHODS AND RESULTS: This study included 16 patients with clinically
      documented typical atrial flutter. Group 1 had 8 patients without and group 2 had
      8 patients with dual AV nodal pathway physiology. Electrical pacing from the
      interatrial septum and low right atrium was performed to evaluate antegrade AV
      node function before and after ablation of the cavotricuspid isthmus. In group 1,
      the AV node conduction properties were similar before and after ablation. In
      group 2, the AV node Wenckebach cycle length and maximal AH interval during low
      right atrium (356+/-58 versus 399+/-49 ms, P=0.008; 303+/-57 versus 376+/-50 ms,
      P=0.008) and interatrial septum (365+/-62 versus 393+/-59 ms, P=0.008; 324+/-52
      versus 390+/-60 ms, P=0.008) pacing were significantly longer after ablation.
      Elimination of the slow pathway after ablation was noted in 2 patients, including
      1 with AV nodal reentrant echo beats. CONCLUSIONS: Radiofrequency ablation of the
      cavotricuspid isthmus was effective in eliminating typical atrial flutter without
      injury of antegrade fast AV node conduction. The atrial musculature in the
      cavotricuspid isthmus significantly contributed to the slow AV node conduction.

PMID- 11571244
TI  - Regional cerebral hyperperfusion and nitric oxide pathway dysregulation in Fabry
      disease: reversal by enzyme replacement therapy.
AB  - BACKGROUND: Fabry disease is an X-linked lysosomal deficiency of alpha
      galactosidase A that results in cellular accumulation of galacto-conjugates such
      as globotriosylceramide, particularly in blood vessels. It is associated with
      early-onset stroke and kidney and heart failure. METHODS AND RESULTS: Using
      [(15)O] H(2)O and PET, we found increased resting regional cerebral blood flow in
      Fabry disease without evidence of occlusive vasculopathy or cerebral
      hypoperfusion. Because nitric oxide is known to play an important role in
      vascular tone and reactivity, we studied plasma nitrate, nitrite, and low
      molecular-weight S-nitrosothiol levels by chemiluminescence. Skin biopsy
      specimens and archived brain tissue were also examined immunohistochemically for
      nitrotyrosine. Plasma nitrate, nitrite, and low-molecular-weight S-nitrosothiol
      were in the normal range; however, enhanced nitrotyrosine staining was observed
      in dermal and cerebral blood vessels. After a double-blind, placebo-controlled
      trial of alpha-galactosidase A therapy, the resting regional cerebral blood flow
      in the treated group was significantly reduced, with a notable decrease of
      nitrotyrosine staining in dermal blood vessels. CONCLUSIONS: These findings
      suggest a chronic alteration of the nitric oxide pathway in Fabry disease, with
      critical protein nitration that is reversible with enzyme replacement therapy.

PMID- 11571245
TI  - Severely impaired cardiac autonomic nervous activity after the Fontan operation.
AB  - BACKGROUND: Elevated neurohumoral activity and an abnormal cardiopulmonary
      response to exercise are well-established characteristics in patients after the
      Fontan operation. However, there have been few studies addressing cardiac
      autonomic nervous activity (CANA) in these patients. METHODS AND RESULTS: We
      evaluated CANA in 63 post-Fontan patients and 44 controls. Cardiac
      parasympathetic nervous activity (PSNA) was estimated by heart rate (HR) changes
      after cholinergic blockade, HR variability, and arterial baroreflex sensitivity.
      Cardiac sympathetic nervous activity was estimated by the heart to mediastinum
      [(123)I]metaiodobenzylguanidine activity ratio (H/M) and the HR increase
      (DeltaHR) after isoproterenol infusion (beta). DeltaHR and peak oxygen uptake
      (VO(2)) were measured by exercise test. There was no difference in beta between
      the Fontan group and controls. PSNA and H/M were markedly lower than in controls
      (P<0.001). PSNA and beta were related to DeltaHR (P<0.05); however, peak VO(2)
      was not correlated with DeltaHR. Neither PSNA nor H/M was associated with
      clinical features, including hemodynamics, type of repair, number of surgical
      procedures, age at Fontan operation, or follow-up period, and administration of
      an angiotensin-converting enzyme inhibitor did not improve the impaired CANA in
      these patients. CONCLUSIONS: After the Fontan procedure, postsynaptic beta
      sensitivity is maintained and is important in DeltaHR during exercise as is PSNA,
      although DeltaHR does not determine exercise capacity. The lack of a relationship
      between CANA and clinical features implies that, in addition to surgical damage,
      the Fontan circulation per se may impair CANA. Angiotensin-converting enzyme
      inhibitor administration does not change this abnormality.

PMID- 11571246
TI  - Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of
      atherosclerosis in apolipoprotein E-deficient mice.
AB  - BACKGROUND: Increasing evidence supports the role of heme oxygenase-1 (HO-1) in
      cytoprotective response and iron homeostasis. The object of this study was to
      investigate whether adenovirus-mediated gene transfer of HO-1 in arteries reduces
      iron overload and inhibits lesion formation in apolipoprotein E (apoE)-deficient
      mice. METHODS AND RESULTS: Infection of rat aortic smooth muscle cells with
      adenovirus carrying the human HO-1 gene (Adv-HO-1) resulted in a high-level
      expression of HO-1 protein, which effectively reduced the hemin-induced iron
      overload in these cells. Adenovirus-mediated gene transfer in arteries in vivo
      was achieved by direct injection of Adv-HO-1 into the left ventricles of
      anesthetized animals. Transgene was expressed in the endothelium and aortic
      lesion of apoE-deficient mice after they had received recombinant adenovirus for
      1 week and gradually decayed during the next 5 weeks. When young apoE-deficient
      mice (14 weeks old) received Adv-HO-1 (2.5 x 10(9) pfu) for 6 weeks, lesions that
      developed in the aortic root or aortic arch were significantly smaller than those
      in control littermates receiving empty viral vector. Furthermore, the iron
      deposition as well as tissue iron content was much less in aortic tissue of Adv
      HO-1-treated mice. The inhibitory effect of HO-1 gene transfer on the progression
      of advanced lesions was also observed in older apoE-deficient mice (20 weeks old)
      receiving Adv-HO-1 intraventricularly. CONCLUSIONS: Overexpression of HO-1 in
      vascular cells facilitates iron metabolism and attenuates development of
      atherosclerosis in apoE-deficient mice.

PMID- 11571247
TI  - Nitric oxide synthase (nNOS) gene transfer modifies venous bypass graft
      remodeling: effects on vascular smooth muscle cell differentiation and superoxide
      production.
AB  - BACKGROUND: Pathological vascular remodeling in venous bypass grafts (VGs)
      results in smooth muscle cell (SMC) intimal hyperplasia and provides the
      substrate for progressive atherosclerosis, the principal cause of late VG
      failure. Nitric oxide (NO) bioactivity is reduced in VGs, in association with
      increased vascular superoxide production, but how these features relate to
      pathological VG remodeling remains unclear. We used gene transfer of the neuronal
      isoform of nitric oxide synthase (nNOS) to investigate how increased NO
      production modulates vascular remodeling in VGs and determined the effects on
      late VG phenotype. METHODS AND RESULTS: New Zealand White rabbits (n=60)
      underwent jugular-carotid interposition bypass graft surgery with intraoperative
      adenoviral gene transfer of nNOS or beta-galactosidase. Vessels were analyzed
      after 3 days (early, to investigate acute injury/inflammation) or 28 days (late,
      to investigate SMC intimal hyperplasia). In early VGs, nNOS gene transfer
      significantly increased NOS activity and substantially reduced adhesion molecule
      expression and inflammatory cell infiltration. In late VGs, recombinant nNOS
      protein was no longer evident, but there were sustained effects on VG remodeling,
      resulting in a striking reduction in SMC intimal hyperplasia, a more
      differentiated intimal SMC phenotype, and reduced vascular superoxide production.
      CONCLUSIONS: Intraoperative nNOS gene transfer has sustained favorable effects on
      VG remodeling and on the vascular phenotype of mature VGs. These findings suggest
      that early, transient modification of the response to vascular injury is a
      powerful approach to modulate VG biology and highlight the potential utility of
      NOS gene transfer as a therapeutic strategy in VGs.

PMID- 11571248
TI  - Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo
      platelet activation than platelet surface P-selectin: studies in baboons, human
      coronary intervention, and human acute myocardial infarction.
AB  - BACKGROUND: Platelet surface P-selectin is considered the "gold standard" marker
      of platelet activation. Degranulated, P-selectin-positive platelets, however,
      aggregate with leukocytes in vitro and rapidly lose surface P-selectin in vivo.
      METHODS AND RESULTS: Flow cytometric tracking of autologous, biotinylated
      platelets in baboons enabled us to directly demonstrate for the first time in
      vivo that (1) infused degranulated platelets very rapidly form circulating
      aggregates with monocytes and neutrophils, and (2) 30 minutes after infusion of
      the degranulated platelets, the percentage of circulating monocytes aggregated
      with infused platelets persist at high levels, whereas the percentage of
      circulating neutrophils aggregated with infused platelets and the platelet
      surface P-selectin of nonaggregated infused platelets return to baseline. We
      therefore performed 2 clinical studies in patients with acute coronary syndromes.
      First, after percutaneous coronary intervention (n=10), there was an increased
      number of circulating monocyte-platelet (and to a lesser extent, neutrophil
      platelet) aggregates but not P-selectin-positive platelets. Second, of 93
      patients presenting to an Emergency Department with chest pain, patients with
      acute myocardial infarction (AMI) (n=9) had more circulating monocyte-platelet
      aggregates (34.2+/-10.3% [mean+/-SEM]) than patients with no AMI (n=84, 19.3+/
      1.4%, P<0.05) and normal control subjects (n=10, 11.5+/-0.8%, P<0.001).
      Circulating P-selectin-positive platelets, however, were not increased in chest
      pain patients with or without AMI. CONCLUSIONS: As demonstrated by 3 independent
      means (in vivo tracking of activated platelets in baboons, human coronary
      intervention, and human AMI), circulating monocyte-platelet aggregates are a more
      sensitive marker of in vivo platelet activation than platelet surface P-selectin.

PMID- 11571249
TI  - Short-term local delivery of an inhibitor of Ras farnesyltransferase prevents
      neointima formation in vivo after porcine coronary balloon angioplasty.
AB  - BACKGROUND: Mitogenic stimuli present at the site of coronary arterial balloon
      injury contribute to the progression and development of a restenotic lesion, many
      signaling through a common pathway involving the small G protein p21(ras). Our
      aim was to demonstrate in biochemical studies that farnesyl protein transferase
      inhibitor III (FPTIII) is an inhibitor of p21(ras) processing and that when it is
      given locally in vivo at the site of coronary balloon injury in a porcine model,
      it can inhibit neointima formation. METHODS AND RESULTS: FPTIII (1 to 25
      micromol/L) concentration-dependently reduced p21(ras) levels in porcine coronary
      artery smooth muscle cell membranes. FPTIII also prevented p42/p44 MAPK
      activation and DNA synthesis in response to platelet-derived growth factor in
      these cells at a concentration of 25 micromol/L. Application of 25 micromol/L
      FPTIII locally for 15 minutes to balloon-injured porcine coronary arteries in
      vivo prevented neointima formation assessed at 4 weeks, reduced proteoglycan
      deposition, and inhibited adventitial hypertrophy. Coronary arteries from FPTIII
      treated pigs had no deterioration in contraction or in endothelium-dependent
      relaxation. CONCLUSIONS: The study demonstrates in the pig that short-term local
      delivery of inhibitors of p21(ras)-dependent mitogenic signal transduction
      prevents restenosis after balloon angioplasty.

PMID- 11571250
TI  - Gap junction blockers decrease defibrillation thresholds without changes in
      ventricular refractoriness in isolated rabbit hearts.
AB  - BACKGROUND: The maintenance and termination of reentry arrhythmias are determined
      by tissue properties such as refractoriness and conduction velocity. Although the
      effects of Na(+) and K(+) channel block on electrophysiological properties and
      defibrillation threshold (DFT) have been studied, little is known about the
      effect of gap junction blockers on defibrillation and tissue electrophysiological
      properties. METHODS AND RESULTS: Triplicate DFTs (volts) were obtained before and
      15 minutes after 4 micromol/L 16-doxyl-stearic acid (16-DSA, n=8), 1 mmol/L 1
      heptanol (n=12) (both gap junction blockers), 3 microg/mL lidocaine (a sodium
      channel blocker) (n=8), and respective controls (n=27) in isolated perfused
      rabbit hearts. DFT decreased after 16-DSA (23+/-14%, P<0.01) and 1-heptanol (21+/
      16%, P<0.01) but increased after lidocaine (26+/-28%, P<0.05). Ventricular
      fibrillation cycle length (VFCL) and QRS duration increased after all 3 agents,
      by 36+/-19% and 44+/-16% (16-DSA), 87+/-42% and 49+/-15% (heptanol), and 57+/-20%
      and 43+/-26% (lidocaine), respectively (all P<0.01). Spatially averaged temporal
      VFCL dispersion decreased significantly after all 3 agents, by 47+/-42% (16-DSA,
      P<0.05), 74+/-19% (1-heptanol, P<0.01), and 82+/-13% (lidocaine, P<0.01),
      respectively. Ventricular effective refractory period and monophasic action
      potential duration at 90% repolarization were unchanged after 16-DSA and 1
      heptanol (P=NS) but increased after lidocaine (16+/-13%, P<0.01, and 6+/-5%,
      P=NS, respectively). There were no significant changes in DFT or any other
      electrophysiological variable in control hearts. CONCLUSIONS: Electrical
      uncoupling by 16-DSA and 1-heptanol significantly lowers DFT and dispersion of
      VFCL without altering refractoriness; lidocaine, at doses resulting in similar
      slowing of conduction, increases DFT.

PMID- 11571251
TI  - Comparison of real-time and intermittent triggered myocardial contrast
      echocardiography for quantification of coronary stenosis severity and transmural
      perfusion gradient.
AB  - BACKGROUND: Both intermittent triggered and real-time myocardial contrast
      echocardiography (MCE) have been proposed to detect impaired myocardial
      perfusion. We compared the ability of these 2 methods to quantify altered
      myocardial blood flow (MBF) and transmural distribution of MBF produced by graded
      coronary stenoses. METHODS AND RESULTS: In 8 open-chest dogs, we created 4 graded
      left anterior descending coronary artery (LAD) stenoses: 3 levels of reduced
      adenosine hyperemia (non-flow-limiting at rest) and 1 grade of flow-limiting at
      rest. Real-time MCE was performed with SonoVue infusion using low-energy power
      pulse inversion (ATL) imaging, whereas ECG-gated intermittent triggered imaging
      used high energy at pulsing intervals from 1:1 to 1:10. LAD signal intensity (SI)
      was plotted versus time by real-time MCE and versus pulsing intervals by
      triggered MCE and was fitted to a 1-exponential function to obtain plateau SI (A)
      and the rate of SI rise (b). Visual detection of decreased opacification was
      equivalent by triggered and real-time MCE. Fluorescent microsphere-derived MBF
      ratio in LAD/left circumflex artery beds demonstrated close correlation with both
      real-time imaging (b, r=0.79; Axb, r=0.81) and triggered imaging (b, r=0.78; Axb,
      r=0.80). The endocardial/epicardial ratio of MBF in the LAD bed demonstrated
      closer correlation with the endocardial/epicardial ratios of b (r=0.71) and Axb
      (r=0.67) obtained by real-time than triggered imaging (b, r=0.42; Axb, r=0.52).
      CONCLUSIONS: Real-time and triggered MCE are equivalent in their ability to
      identify coronary stenosis and quantify altered MBF.

PMID- 11571252
TI  - c-Jun decreases voltage-gated K(+) channel activity in pulmonary artery smooth
      muscle cells.
AB  - BACKGROUND: Activity of voltage-gated K(+) (K(v)) channels controls membrane
      potential (E(m)) that regulates cytosolic free Ca(2+) concentration
      ([Ca(2+)](cyt)) by regulating voltage-dependent Ca(2+) channel function. A rise
      in [Ca(2+)](cyt) in pulmonary artery smooth muscle cells (PASMCs) triggers
      vasoconstriction and stimulates PASMC proliferation. Whether c-Jun, a
      transcription factor that stimulates cell proliferation, affects K(v) channel
      activity in PASMCs was investigated. METHODS AND RESULTS: Infection of primary
      cultured PASMCs with an adenoviral vector expressing c-jun increased the protein
      level of c-Jun and reduced K(v) currents (I(K(V))) compared with control cells
      (infected with an empty adenovirus). Using single-cell reverse transcription
      polymerase chain reaction, we observed that the mRNA level of Kv1.5 and the
      current density of I(K(V)) were both attenuated in c-jun-infected PASMCs compared
      with control cells and cells infected with antisense c-jun. Overexpression of c
      Jun also upregulated protein expression of Kvbeta(2) and accelerated I(K(V))
      inactivation. Furthermore, E(m) was more depolarized and [(3)H]thymidine
      incorporation was greater in PASMCs infected with c-jun than in control cells and
      cells infected with antisense c-jun. CONCLUSIONS: These results suggest that c
      Jun-mediated PASMC proliferation is associated with a decrease in I(K(V)). The
      resultant membrane depolarization increases [Ca(2+)](cyt) and enhances PASMC
      growth.

PMID- 11571253
TI  - Primary prevention of sudden death with implantable defibrillator therapy in
      patients with cardiac disease: Can we afford to do it? (Can we afford not to?).

PMID- 11571254
TI  - Are ACE inhibitors a "magic bullet" against oxidative stress?

PMID- 11571255
TI  - Anomalous origin of the left main coronary artery from the main pulmonary artery
      in a young adult.

PMID- 11571256
TI  - AHA/ACC Scientific Statement: AHA/ACC guidelines for preventing heart attack and
      death in patients with atherosclerotic cardiovascular disease: 2001 update: A
      statement for healthcare professionals from the American Heart Association and
      the American College of Cardiology.

PMID- 11571257
TI  - Myocardial ischemia on thallium scintigraphy in hypertrophic cardiomyopathy:
      predictor of sudden cardiac death.

PMID- 11571259
TI  - American Heart Association Advisory, "Wine and Your heart," is not science-based.

PMID- 11571260
TI  - Collateral flow index to assess myocardial viability: Chugh's hypothesis
      revisited.

PMID- 11571261
TI  - Mechanism of Arterial Infection by Chlamydia pneumoniae.

PMID- 11571262
TI  - Clopidogrel versus aspirin after cardiac surgery.

PMID- 11571263
TI  - September 11, 2001.

PMID- 11571264
TI  - Physicians, nurses, paramedics, medics, and hospitals respond to tragedies in New
      York and DC.

PMID- 11571265
TI  - Stable gene expression from a mammalian artificial chromosome.
AB  - We have investigated the potential of PAC-based vectors as a route to the
      incorporation of a gene in a mammalian artificial chromosome (MAC). Previously we
      demonstrated that a PAC (PAC7c5) containing alpha-satellite DNA generated
      mitotically stable MACs in human cells. To determine whether a functional HPRT
      gene could be assembled in a MAC, PAC7c5 was co-transfected with a second PAC
      containing a 140 kb human HPRT gene into HPRT-deficient HT1080 cells. Lines were
      isolated containing a MAC hybridizing with both alpha-satellite and HPRT probes.
      The MACs segregated efficiently, associated with kinetochore proteins and stably
      expressed HPRT message after 60 days without selection. Complementation of the
      parental HPRT deficiency was confirmed phenotypically by growth on HAT selection.
      These results suggest that MACs could be further developed for delivering a range
      of genomic copies of genes into cells and that stable transgene expression can be
      achieved.

PMID- 11571266
TI  - Biologically active APRIL is secreted following intracellular processing in the
      Golgi apparatus by furin convertase.
AB  - Tumor necrosis factor (TNF) ligand family members are synthesized as
      transmembrane proteins, and cleavage of the membrane-anchored proteins from the
      cell surface is frequently observed. The TNF-related ligands APRIL and BLyS and
      their cognate receptors BCMA/TACI form a two ligand/two receptor system that has
      been shown to participate in B- and T-cell stimulation. In contrast to BLyS,
      which is known to be cleaved from the cell surface, we found that APRIL is
      processed intracellularly by furin convertase. Blockage of protein transport from
      the endoplasmic reticulum to the Golgi apparatus by Brefeldin A treatment
      abrogated APRIL processing, whereas monensin, an inhibitor of post-Golgi
      transport, did not interfere with cleavage of APRIL, but blocked secretion of
      processed APRIL. Thus, APRIL shows a unique maturation pathway among the TNF
      ligand family members, as it not detectable as a membrane-anchored protein at the
      cell surface, but is processed in the Golgi apparatus prior to its secretion.

PMID- 11571267
TI  - Histones H3/H4 form a tight complex with the inner nuclear membrane protein LBR
      and heterochromatin protein 1.
AB  - We have recently shown that heterochromatin protein 1 (HP1) interacts with the
      nuclear envelope in an acetylation-dependent manner. Using purified components
      and in vitro assays, we now demonstrate that HP1 forms a quaternary complex with
      the inner nuclear membrane protein LBR and a sub-set of core histones. This
      complex involves histone H3/H4 oligomers, which mediate binding of LBR to HP1 and
      cross-link these two proteins that do not interact directly with each other.
      Consistent with previous observations, HP1 and LBR binding to core histones is
      strongly inhibited when H3/H4 are modified by recombinant CREB-binding protein,
      revealing a new mechanism for anchoring domains of under-acetylated chromatin to
      the inner nuclear membrane.

PMID- 11571268
TI  - RanBP3 influences interactions between CRM1 and its nuclear protein export
      substrates.
AB  - We investigated the role of RanBP3, a nuclear member of the Ran-binding protein 1
      family, in CRM1-mediated protein export in higher eukaryotes. RanBP3 interacts
      directly with CRM1 and also forms a trimeric complex with CRM1 and RanGTP.
      However, RanBP3 does not bind to CRM1 like an export substrate. Instead, it can
      stabilize CRM1-export substrate interaction. Nuclear RanBP3 stimulates CRM1
      dependent protein export in permeabilized cells. These data indicate that RanBP3
      functions by a novel mechanism as a cofactor in recognition and export of certain
      CRM1 substrates. In vitro, RanBP3 binding to CRM1 affects the relative affinity
      of CRM1 for different substrates.

PMID- 11571269
TI  - Visualization of recombination intermediates produced by RAD52-mediated single
      strand annealing.
AB  - Double-strand breaks (DSBs) occur frequently during DNA replication. They are
      also caused by ionizing radiation, chemical damage or as part of the series of
      programmed events that occur during meiosis. In yeast, DSB repair requires RAD52,
      a protein that plays a critical role in homologous recombination. Here we
      describe the actions of human RAD52 protein in a model system for single-strand
      annealing (SSA) using tailed (i.e. exonuclease resected) duplex DNA molecules.
      Purified human RAD52 protein binds resected DSBs and promotes associations
      between complementary DNA termini. Heteroduplex intermediates of these
      recombination reactions have been visualized by electron microscopy, revealing
      the specific binding of multiple rings of RAD52 to the resected termini and the
      formation of large protein complexes at heteroduplex joints formed by RAD52
      mediated annealing.

PMID- 11571270
TI  - Dynactin-membrane interaction is regulated by the C-terminal domains of
      p150(Glued).
AB  - Dynactin has been proposed to link the microtubule-associated motor cytoplasmic
      dynein with membranous cargo; however, the mechanism by which dynactin-membrane
      interaction is regulated is unknown. Here we show that dynein and dynactin exist
      in discrete cytosolic and membrane-bound states in the filamentous fungus
      Neurospora crassa. Results from in vitro membrane-binding studies show that
      dynein and dynactin-membrane interaction is co-dependent. p150(Glued) of dynactin
      has been shown to interact with dynein intermediate chain and dynactin Arp1
      filament; however, it is not known to play a direct role in membrane binding. In
      this report we describe our analysis of 43 p150(Glued) mutants, and we show that
      C-terminal deletions which remove the terminal coiled-coil (CC2) and basic domain
      (BD) result in constitutive dynactin-membrane binding. In vitro addition of
      recombinant p150(Glued) CC2+BD protein blocks dynactin-membrane binding. We
      propose that the C-terminal domains of p150(Glued) regulate dynactin-membrane
      binding through a steric mechanism that controls accessibility of the Arp1
      filament of dynactin to membranous cargo.

PMID- 11571271
TI  - Ubiquitin-associated (UBA) domains in Rad23 bind ubiquitin and promote inhibition
      of multi-ubiquitin chain assembly.
AB  - Rad23 is a DNA repair protein that promotes the assembly of the nucleotide
      excision repair complex. Rad23 can interact with the 26S proteasome through an N
      terminal ubiquitin-like domain, and inhibits the assembly of substrate-linked
      multi-ubiquitin (multi-Ub) chains in vitro and in vivo. Significantly, Rad23 can
      bind a proteolytic substrate that is conjugated to a few ubiquitin (Ub) moieties.
      We report here that two ubiquitin-associated (UBA) domains in Rad23 form non
      covalent interactions with Ub. A mutant that lacked either UBA sequence was
      capable of blocking the assembly of substrate-linked multi-Ub chains, although a
      mutant that lacked both UBA domains was significantly impaired. These studies
      suggest that the interaction with Ub is required for Rad23 activity, and that
      other UBA-containing proteins may have a similar function.

PMID- 11571272
TI  - Florid plaques in ovine PrP transgenic mice infected with an experimental ovine
      BSE.
AB  - The occurrence of the variant Creutzfeldt-Jakob disease (vCJD), related to bovine
      spongiform encephalopathy (BSE), raises the important question of the sources of
      human contamination. The possibility that sheep may have been fed with BSE
      contaminated foodstuff raises the serious concern that BSE may now be present in
      sheep without being distinguishable from scrapie. Sensitive models are urgently
      needed given the dramatic consequences of such a possible contamination on animal
      and human health. We inoculated transgenic mice expressing the ovine PrP gene
      with a brain homogenate from sheep experimentally infected with BSE. We found
      numerous typical florid plaques in their brains. Such florid plaques are a
      feature of vCJD in humans and experimental BSE infection in macaques. Our
      observation represents the first description, after a primary infection, of this
      hallmark in a transgenic mouse model. Moreover, these mice appear to be a
      promising tool in the search for BSE in sheep.

PMID- 11571273
TI  - Physical and functional association of SU(VAR)3-9 and HDAC1 in Drosophila.
AB  - Modification of histones can have a dramatic impact on chromatin structure and
      function. Acetylation of lysines within the N-terminal tail of the histone
      octamer marks transcriptionally active regions of the genome whereas
      deacetylation seems to play a role in transcriptional silencing. Recently, the
      methylation of the histone tails has also been shown to be important for
      transcriptional regulation and chromosome structure. Here we show by
      immunoaffinity purification that two activities important for chromatin-mediated
      gene silencing, the histone methyltransferase SU(VAR)3-9 and the histone
      deacetylase HDAC1, associate in vivo. The two activities cooperate to methylate
      pre-acetylated histones. Both enzymes are modifiers of position effect
      variegation and interact genetically in flies. We suggest a model in which the
      concerted histone deacetylation and methylation by a SU(VAR)3-9/HDAC1-containing
      complex leads to a permanent silencing of transcription in particular areas of
      the genome.

PMID- 11571274
TI  - ATM phosphorylates histone H2AX in response to DNA double-strand breaks.
AB  - A very early step in the response of mammalian cells to DNA double-strand breaks
      is the phosphorylation of histone H2AX at serine 139 at the sites of DNA damage.
      Although the phosphatidylinositol 3-kinases, DNA-PK (DNA-dependent protein
      kinase), ATM (ataxia telangiectasia mutated), and ATR (ATM and Rad3-related),
      have all been implicated in H2AX phosphorylation, the specific kinase involved
      has not yet been identified. To definitively identify the specific kinase(s) that
      phosphorylates H2AX in vivo, we have utilized DNA-PKcs-/- and Atm-/- cell lines
      and mouse embryonic fibroblasts. We find that H2AX phosphorylation and nuclear
      focus formation are normal in DNA-PKcs-/- cells and severely compromised in Atm-/
      cells. We also find that ATM can phosphorylate H2AX in vitro and that ectopic
      expression of ATM in Atm-/- fibroblasts restores H2AX phosphorylation in vivo.
      The minimal H2AX phosphorylation in Atm-/- fibroblasts can be abolished by low
      concentrations of wortmannin suggesting that DNA-PK, rather than ATR, is
      responsible for low levels of H2AX phosphorylation in the absence of ATM. Our
      results clearly establish ATM as the major kinase involved in the phosphorylation
      of H2AX and suggest that ATM is one of the earliest kinases to be activated in
      the cellular response to double-strand breaks.

PMID- 11571275
TI  - p38 MAPK regulates group IIa phospholipase A2 expression in interleukin-1beta 
      stimulated rat neonatal cardiomyocytes.
AB  - Group IIa phospholipase A(2) (GIIa PLA(2)) is released by some cells in response
      to interleukin-1beta. The purpose of this study was to determine whether
      interleukin-1beta would stimulate the synthesis and release of GIIa PLA(2) from
      cardiomyocytes, and to define the role of p38 MAPK and cytosolic PLA(2) in the
      regulation of this process. Whereas GIIa PLA(2) mRNA was not identified in
      untreated cells, exposure to interleukin-1beta resulted in the sustained
      expression of GIIa PLA(2) mRNA. Interleukin-1beta also stimulated a progressive
      increase in cellular and extracellular GIIa PLA(2) protein levels and increased
      extracellular PLA(2) activity 70-fold. In addition, interleukin-1beta stimulated
      the p38 MAPK-dependent activation of the downstream MAPK-activated protein
      kinase, MAPKAP-K2. Treatment with the p38 MAPK inhibitor, SB202190, decreased
      interleukin-1beta stimulated MAPKAP-K2 activity, GIIa PLA(2) mRNA expression,
      GIIa PLA(2) protein synthesis, and the release of extracellular PLA(2) activity.
      Infection with an adenovirus encoding a constitutively active form of MKK6,
      MKK6(Glu), which selectively phosphorylates p38 MAPK, induced cellular GIIa
      PLA(2) protein synthesis and the release of GIIa PLA(2) and increased
      extracellular PLA(2) activity 3-fold. In contrast, infection with an adenovirus
      encoding a phosphorylation-resistant MKK6, MKK6(A), did not result in GIIa PLA(2)
      protein synthesis or release by unstimulated cardiomyocytes. In addition,
      infection with an adenovirus encoding MKK6(A) abrogated GIIa PLA(2) protein
      synthesis and release by interleukin-1beta-stimulated cells. These results
      provide direct evidence that p38 MAPK activation was necessary for interleukin
      1beta-induced synthesis and release of GIIa PLA(2) by cardiomyocytes.

PMID- 11571276
TI  - Determination of the RNA binding specificity of the heterogeneous nuclear
      ribonucleoprotein (hnRNP) H/H'/F/2H9 family.
AB  - Members of the heterogeneous nuclear ribonucleoprotein (hnRNP) H protein family,
      H, H', F, and 2H9, are involved in pre-mRNA processing. We analyzed the assembly
      of these proteins from splicing extracts onto four RNA regulatory elements as
      follows: a high affinity hnRNP A1-binding site (WA1), a sequence involved in Rev
      dependent export (p17gag INS), an exonic splicing silencer from the beta
      tropomyosin gene, and an intronic splicing regulator (downstream control sequence
      (DCS) from the c-src gene. The entire family binds the WA1, instability (INS),
      and beta-tropomyosin substrates, and the core-binding site for each is a run of
      three G residues followed by an A. Transfer of small regions containing this
      sequence to a substrate lacking hnRNP H binding activity is sufficient to promote
      binding of all family members. The c-src DCS has been shown to assemble hnRNP H,
      not hnRNP F, from HeLa cell extracts, and we show that hnRNP 2H9 does not bind
      this element. The DCS contains five G residues followed by a C. Mutation of the C
      to an A changes the specificity of the DCS from a substrate that binds only hnRNP
      H/H' to a binding site for all hnRNP H family members. We conclude that the
      sequence GGGA is recognized by all hnRNP H family proteins.

PMID- 11571277
TI  - PrPC directly interacts with proteins involved in signaling pathways.
AB  - The cellular prion protein (PrP(C)) is a conserved glycoprotein predominantly
      expressed in neuronal cells. Its purpose in living cells is still enigmatic. To
      elucidate on its cellular function, we performed a yeast two-hybrid screen for
      interactors. We used murine PrP(C) (amino acids 23-231) as bait to search a mouse
      brain cDNA expression library. Several interaction partners were identified.
      Three of them with a high homology to known sequences were further characterized.
      These candidates were the neuronal phosphoprotein synapsin Ib, the adaptor
      protein Grb2, and the still uncharacterized prion interactor Pint1. The in vivo
      interaction of the three proteins with PrP(C) was confirmed by co
      immunoprecipitation assays with recombinant and authentic proteins in mammalian
      cells. The binding regions were mapped using truncated PrP constructs. As both
      synapsin Ib and Grb2 are implicated in neuronal signaling processes, our findings
      further strengthen the putative role of the prion protein in signal transduction.

PMID- 11571278
TI  - Ligation of integrin alpha 3beta 1 by laminin 5 at the wound edge activates Rho
      dependent adhesion of leading keratinocytes on collagen.
AB  - Wounding of the epidermis signals the transition of keratinocytes from quiescent
      anchorage on endogenous basement membrane laminin 5 to migration on exposed
      dermal collagen. In this study, we attempt to characterize activation signals
      that transform quiescent keratinocytes into migratory leading cells at the wound
      edge. Previously, we reported that adhesion and spreading on collagen via
      integrin alpha(2)beta(1) by cultured human foreskin keratinocytes (HFKs) requires
      RhoGTP, a regulator of actin stress fibers. In contrast, adhesion and spreading
      on laminin 5 requires integrins alpha(3)beta(1) and alpha(6)beta(4) and is
      dependent on phosphoinositide 3-hydroxykinase (Nguyen, B. P., Gil, S. G., and
      Carter, W. G. (2000) J. Biol. Chem. 275, 31896-31907). Here, we report that
      quiescent HFKs do not adhere to collagen but adhere and spread on laminin 5. By
      using collagen adhesion as one criterion for conversion to a "leading wound
      cell," we found that activation of collagen adhesion requires elevation of
      RhoGTP. Adhesion of quiescent HFKs to laminin 5 via integrin alpha(3)beta(1) and
      alpha(6)beta(4) is sufficient to increase levels of RhoGTP required for adhesion
      and spreading on collagen. Consistently, adhesion of quiescent HFKs to laminin 5,
      but not collagen, also promotes expression of the precursor form of laminin 5, a
      characteristic of leading keratinocytes in the epidermal outgrowth. We suggest
      that wounding of quiescent epidermis initiates adhesion and spreading of
      keratinocytes at the wound edge on endogenous basement membrane laminin 5 via
      alpha(3)beta(1) and alpha(6)beta(4) in a Rho-independent mechanism. Spreading on
      endogenous laminin 5 via alpha(3)beta(1) is necessary but not sufficient to
      elevate expression of precursor laminin 5 and RhoGTP, allowing for subsequent
      collagen adhesion via alpha(2)beta(1), all characteristics of leading
      keratinocytes in the epidermal outgrowth.

PMID- 11571279
TI  - Fc gamma RIIB1/SHIP-mediated inhibitory signaling in B cells involves lipid
      rafts.
AB  - One type of membrane microdomain, enriched in glycosphingolipids and cholesterol
      and referred to as lipid rafts, has been implicated in the generation of
      activating signals triggered by a variety of stimuli. Several laboratories,
      including ours, have recently demonstrated that the B cell receptor (BCR)
      inducibly localizes to the rafts upon activation and that functional lipid rafts
      are important for BCR-mediated "positive" signaling. In the later phases of the
      immune response, coligation of the BCR and the inhibitory receptor Fc gamma RIIB1
      leads to potent inhibition of BCR-induced positive signaling through the
      recruitment of the inositol phosphatase SHIP to Fc gamma RIIB1. One potential
      model is that the Fc gamma RIIB1 itself might be excluded from the rafts basally
      and that destabilization of raft-dependent BCR signaling might be part of the
      mechanism for the Fc gamma RIIB1-mediated negative regulation. We tested this
      hypothesis and observed that preventing BCR raft localization is not the
      mechanism for this inhibition. Surprisingly, a fraction of Fc gamma RIIB1 is
      constitutively localized in the rafts and increases further after BCR + FcR
      coligation. SHIP is actively recruited to lipid rafts under negative stimulation
      conditions, and the majority of Fc gamma RIIB1-SHIP complexes localize to lipid
      rafts compared with non-raft regions of the plasma membrane. This suggested that
      this negative feedback loop is also initiated in the lipid rafts. Despite its
      basal localization to the rafts, Fc gamma RIIB1 did not become phosphorylated
      after BCR alone cross-linking and did not colocalize with the BCR that moves to
      rafts upon BCR engagement alone (positive signaling conditions), perhaps
      suggesting the existence of different subsets of rafts. Taken together, these
      data suggest that lipid rafts play a role in both the positive signaling via the
      BCR as well as the inhibitory signaling through Fc gamma RIIB1/SHIP.

PMID- 11571280
TI  - Polycomblike PHD fingers mediate conserved interaction with enhancer of zeste
      protein.
AB  - The products of Polycomb group (PcG) genes are required for the epigenetic
      repression of a number of important developmental regulatory genes, including
      homeotic genes. Enhancer of zeste (E(Z)) is a Drosophila PcG protein that
      previously has been shown to bind directly to another PcG protein, Extra Sex
      Combs (ESC), and is present along with ESC in a 600-kDa complex in Drosophila
      embryos. Using yeast two-hybrid and in vitro binding assays, we show that E(Z)
      binds directly to another PcG protein, Polycomblike (PCL). PCL.E(Z) interaction
      is shown to be mediated by the plant homeodomain (PHD) fingers domain of PCL,
      providing evidence that this motif can act as an independent protein interaction
      domain. An association was also observed between PHF1 and EZH2, human homologs of
      PCL and E(Z), respectively, demonstrating the evolutionary conservation of this
      interaction. E(Z) was found to not interact with the PHD domains of three
      Drosophila trithorax group (trxG) proteins, which function to maintain the
      transcriptional activity of homeotic genes, providing evidence for the
      specificity of the interaction of E(Z) with the PCL PHD domain.
      Coimmunoprecipitation and gel filtration experiments demonstrate in vivo
      association of PCL with E(Z) and ESC in Drosophila embryos. We discuss the
      implications of PCL association with ESC.E(Z) complexes and the possibility that
      PCL may either be a subunit of a subset of ESC.E(Z) complexes or a subunit of a
      separate complex that interacts with ESC.E(Z) complexes.

PMID- 11571281
TI  - Ligand-regulated binding of FAP68 to the hepatocyte growth factor receptor.
AB  - We have used the yeast two-hybrid system to identify proteins that interact with
      the intracellular portion of the hepatocyte growth factor (HGF) receptor (Met).
      We isolated a human cDNA encoding a novel protein of 68 kDa, which we termed
      FAP68. This protein is homologous to a previously described FK506-binding protein
      associated protein, FAP48, which derives from an alternative spliced form of the
      same cDNA, lacking an 85-nucleotide exon and leading to an early stop codon. Here
      we show that epithelial cells, in which the HGF receptor is naturally expressed,
      contain FAP68 and not FAP48 proteins. FAP68 binding to Met requires the last 30
      amino acids of the C-terminal tail, which are unique to the HGF receptor. Indeed,
      FAP68 does not interact with related tyrosine kinases of the Met and insulin
      receptor families. FAP68 interacts specifically with the inactive form of HGF
      receptor, such as a kinase-defective receptor or a dephosphorylated wild type
      receptor. In vivo, endogenous FAP68 can be coimmunoprecipitated with the HGF
      receptor in the absence of stimuli and not upon HGF stimulation. Thus, FAP68
      represents a novel type of effector that interacts with the inactive HGF receptor
      and is released upon receptor phosphorylation. Free FAP68 exerts a specific
      stimulatory activity toward the downstream target p70 S6 protein kinase (p70S6K).
      Significantly, nonphosphorylated HGF receptor prevents FAP68 from stimulating
      p70S6K. These data suggest a role for FAP68 in coupling HGF receptor signaling to
      the p70S6K pathway.

PMID- 11571282
TI  - Intracellular distribution of lysosomal sialidase is controlled by the
      internalization signal in its cytoplasmic tail.
AB  - Sialidase (neuraminidase), encoded by the neu-1 gene in the major
      histocompatibility complex locus catalyzes the intralysosomal degradation of
      sialylated glycoconjugates. Inherited deficiency of sialidase results in
      sialidosis or galactosialidosis, both severe metabolic disorders associated with
      lysosomal storage of oligosaccharides and glycopeptides. Sialidase also plays an
      important role in cellular signaling and is specifically required for the
      production of cytokine interleukin-4 by activated T lymphocytes. In these cells,
      neu-1-encoded sialidase activity is increased on the cell surface, suggesting
      that a specific mechanism regulates sorting of this enzyme to the plasma
      membrane. We investigated that mechanism by first showing that sialidase contains
      the internalization signal found in lysosomal membrane proteins targeted to
      endosomes via clathrin-coated pits. The signal consists of a C-terminal
      tetrapeptide (412)YGTL(415), with Tyr(412) and Leu(415) essential for endocytosis
      of the enzyme. We further demonstrated that redistribution of sialidase from
      lysosomes to the cell surface of activated lymphocytes is accompanied by
      increased reactivity of the enzyme with anti-phosphotyrosine antibodies. We
      speculate that phosphorylation of Tyr(412) results in inhibition of sialidase
      internalization in activated lymphocytes.

PMID- 11571283
TI  - Homeostasis in mRNA initiation: wheat germ poly(A)-binding protein lowers the
      activation energy barrier to initiation complex formation.
AB  - Previous kinetic binding studies of wheat germ protein synthesis eukaryotic
      initiation factor iso4F (eIFiso4F) and its subunit, eIF4E, with m(7)GTP and mRNA
      analogues indicated that binding occurred by a two-step process with the first
      step being too fast to measure by stopped-flow techniques (). Further equilibrium
      studies showed that poly(A)-binding protein (PABP) enhanced the cap binding of
      eIFiso4F about 40-fold. The kinetic effects of PABP on cap binding and the
      temperature dependence of this reaction were measured and compared. Fluorescence
      stopped-flow studies of the PABP.eIFiso4F protein complex with cap show a
      concentration-independent conformational change. PABP did not significantly
      increase the rate of the conformational change, and because the initial second
      order binding is essentially diffusion-controlled, the enhancement of cap
      affinity must reside in the dissociation rate. The dissociation rate was more
      than 5-fold slower in the presence of PABP. The temperature dependence of the cap
      binding reaction was markedly reduced in the presence of PABP. The reduced energy
      barrier for formation of a cap.eIFiso4F complex suggests a more stable platform
      for further initiation complex formation and a possible means of adapting to
      varying temperature conditions.

PMID- 11571284
TI  - p11 expression in human bronchial epithelial cells is increased by nitric oxide
      in a cGMP-dependent pathway involving protein kinase G activation.
AB  - The effect of nitric oxide on p11 expression was studied in an immortalized human
      bronchial epithelial cell line (BEAS-2B cells). Three nitric oxide donors were
      used: spermine NONOate (SP), (+/-)-S-nitroso-N-acetylpenicillamine (SNAP), and S
      nitrosoglutathione (SNOG). All three nitric oxide donors had similar effects
      resulting in dose-dependent and time-dependent accumulation of p11 protein and an
      increase of steady-state p11 mRNA. Studies using a reporter gene containing the
      region from -1499 to +89 of the p11 promoter demonstrated an increase in
      transcriptional activity after stimulation with NO donors for 4 h. These effects
      were abolished at the promoter and protein level using protein kinase G
      inhibitors (KT5823 and R(p)-8-pCPT-cGMPS). Incubation of transfected cells with a
      cell permeable cGMP analogue (8-Br-cGMP) resulted in a dose-related increase of
      promoter activity. An electrophoretic mobility shift assay of nuclear proteins
      extracted from BEAS-2B cells identified an AP-1 site located at -82 to -77 of the
      p11 promoter region as an NO- and cGMP- dependent response element. These data
      were confirmed using a c-jun dominant negative mutant vector and a c-jun
      expression plasmid. Therefore, we conclude that nitric oxide-induced p11
      expression in human bronchial epithelial cells is mediated at least in part
      through increased binding of activator protein one to the p11 promoter.

PMID- 11571285
TI  - Internalin B activates nuclear factor-kappa B via Ras, phosphoinositide 3-kinase,
      and Akt.
AB  - Internalin B (InlB), a 630-amino acid protein loosely attached to the surface of
      Listeria monocytogenes, participates in the entry of the bacterium into mammalian
      cells. This process requires the activation of phosphoinositide (PI) 3-kinase by
      InlB. Previously, we demonstrated that InlB activates the transcription factor
      Nuclear Factor-kappaB in murine J774 macrophage-like cells, an event that also
      requires PI 3-kinase. Here we have further investigated this phenomenon. InlB
      activated the small G-protein Ras in J774 cells. Inhibition of Ras with the
      farnesyltransferase inhibitor manumycin A inhibited NF-kappaB activation and the
      recruitment of the p85 subunit of PI 3-kinase, implying that Ras is required for
      PI 3-kinase activation. InlB also activated the PI 3-kinase downstream effector,
      Akt, as assessed by increased phosphorylation of Akt on serine 473. Transfection
      of Hep2 cells with dominant negative Ras N17 or dominant negative Akt inhibited
      the induction of a reporter gene linked to the interleukin-8 promoter by InlB.
      Furthermore, the Ras inhibitor manumycin A, the PI 3-kinase inhibitor LY294002,
      and an Akt inhibitor all blocked the induction of interleukin-8 by InlB. Our
      study is the first report of a bacterial product activating a pathway involving
      Ras, PI 3-kinase, and Akt, which leads to NF-kappaB activation. This process
      could be involved in host defense or the inhibition of apoptosis during
      infection.

PMID- 11571286
TI  - Alternate FGF2-ERK1/2 signaling pathways in retinal photoreceptor and glial cells
      in vitro.
AB  - Basic fibroblast growth factor (FGF2) stimulates photoreceptor survival in vivo
      and in vitro, but the molecular signaling mechanism(s) involved are unknown.
      Immunohistochemical and immunoblotting analyses of pure photoreceptors, inner
      retinal neurons, and Muller glial cells (MGC) in vitro revealed differential
      expression of the high affinity FGF receptors (FGFR1-4), as well as many
      cytoplasmic signaling intermediates known to mediate the extracellular signal
      regulated kinase (ERK1/2) pathway. FGF2-induced tyrosine phosphorylation in vitro
      exhibited distinct profiles for each culture type, and FGF2-induced ERK1/2
      activation was observed for all three preparations. Whereas U0126, a specific
      inhibitor of ERK kinase (MEK), completely abolished FGF2-induced ERK1/2 tyrosine
      phosphorylation and survival in cultured photoreceptors, persistent ERK1/2
      phosphorylation was observed in cultured inner retinal cells and MGC. Furthermore
      U0126 treatment entirely blocked nerve growth factor-induced ERK1/2 activation in
      MGC, as well as FGF2-induced ERK1/2 activation in cerebral glial cells. Taken
      together, these data indicate that FGF2-induced ERK1/2 activation is entirely
      mediated by MEK within photoreceptors, which is responsible for FGF2-stimulated
      photoreceptor survival. In contrast, inner retina/glia possess alternative, cell
      type, and growth factor-specific MEK-independent ERK1/2 activation pathways.
      Hence signaling and biological effects elicited by FGF2 within retina are
      mediated by cell type-specific pathways.

PMID- 11571287
TI  - Effect of thymine glycol on transcription elongation by T7 RNA polymerase and
      mammalian RNA polymerase II.
AB  - Thymine glycols are formed in DNA by exposure to ionizing radiation or oxidative
      stress. Although these lesions are repaired by the base excision repair pathway,
      they have been shown also to be subject to transcription-coupled repair. A
      current model for transcription-coupled repair proposes that RNA polymerase II
      arrested at a DNA lesion provides a signal for recruitment of the repair enzymes
      to the lesion site. Here we report the effect of thymine glycol on transcription
      elongation by T7 RNA polymerase and RNA polymerase II from rat liver. DNA
      substrates containing a single thymine glycol located either in the transcribed
      or nontranscribed strand were used to carry out in vitro transcription. We found
      that thymine glycol in the transcribed strand blocked transcription elongation by
      T7 RNA polymerase approximately 50% of the time but did not block RNA polymerase
      II. Thymine glycol in the nontranscribed strand did not affect transcription by
      either polymerase. These results suggest that arrest of RNA polymerase elongation
      by thymine glycol is not necessary for transcription-coupled repair of this
      lesion. Additional factors that recognize and bind thymine glycol in DNA may be
      required to ensure RNA polymerase arrest and the initiation of transcription
      coupled repair in vivo.

PMID- 11571288
TI  - Nerve growth factor uses Ras/ERK and phosphatidylinositol 3-kinase cascades to up
      regulate the N-methyl-D-aspartate receptor 1 promoter.
AB  - We reported previously that nerve growth factor (NGF) up-regulates activity of
      the N-methyl-D-aspartate receptor 1 (NR1) promoter. We have explored the pathways
      and nuclear targets of NGF signaling in regulating the NR1 promoter. PD98059 and
      wortmannin, but not rapamycin, significantly attenuated NGF-induced
      transcriptional activity from an NR1 promoter-luciferase construct. Coexpressing
      constitutively active forms of Ras, Raf, or MAPK/ERK kinase 1 (MEK1) increased
      promoter activity dramatically. The MEK1-induced increase was largely prevented
      by mutations of the tandem GC boxes in the promoter. Promoter activity was also
      increased significantly by coexpressed GC box-binding proteins (Sp1, 3, or 4) in
      nonstimulated PC12 cells. Either an extracellular signal-regulated kinase-1
      (ERK1)- or Sp1-specific antibody coprecipitated Sp1 with ERKs, and the
      coprecipitation was enhanced significantly by NGF treatment of PC12 cells. ERK2
      also incorporated radioactivity of [gamma(32)P]ATP into recombinant Sp1. However,
      ERK2-treated Sp1 and PC12 nuclear extracts or nuclear extracts from NGF-treated
      cells exhibited reduced binding to the promoter or a consensus GC box. Our
      results suggest that NGF utilizes both the Ras/ERK and phosphatidylinositol 3
      kinase pathways to up-regulate NR1 promoter activity and that Sp1 is a novel
      substrate of NGF-activated ERKs. NGF-increased NR1 promoter activity may involve
      a complicated mechanism of Sp1 phosphorylation and possible transcription factor
      exchange.

PMID- 11571289
TI  - Nocodazole inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes via
      a microtubule-independent mechanism.
AB  - Insulin stimulates glucose transport in adipocytes and muscle cells by triggering
      redistribution of the GLUT4 glucose transporter from an intracellular perinuclear
      location to the cell surface. Recent reports have shown that the microtubule
      depolymerizing agent nocodazole inhibits insulin-stimulated glucose transport,
      implicating an important role for microtubules in this process. In the present
      study we show that 2 microm nocodazole completely depolymerized microtubules in
      3T3-L1 adipocytes, as determined morphologically and biochemically, resulting in
      dispersal of the perinuclear GLUT4 compartment and the Golgi apparatus. However,
      2 microm nocodazole did not significantly effect either the kinetics or magnitude
      of insulin-stimulated glucose transport. Consistent with previous studies, higher
      concentrations of nocodazole (10-33 microm) significantly inhibited basal and
      insulin-stimulated glucose uptake in adipocytes. This effect was not likely the
      result of microtubule depolymerization because in the presence of taxol, which
      blocked nocodazole-induced depolymerization of microtubules as well as the
      dispersal of the perinuclear GLUT4 compartment, the inhibitory effect of 10-33
      microm nocodazole on insulin-stimulated glucose uptake prevailed. Despite the
      decrease in insulin-stimulated glucose transport with 33 microm nocodazole we did
      not observe inhibition of insulin-stimulated GLUT4 translocation to the cell
      surface under these conditions. Consistent with a direct effect of nocodazole on
      glucose transporter function we observed a rapid inhibitory effect of nocodazole
      on glucose transport activity when added to either 3T3-L1 adipocytes or to
      Chinese hamster ovary cells at 4 degrees C. These studies reveal a new and
      unexpected effect of nocodazole in mammalian cells which appears to occur
      independently of its microtubule-depolymerizing effects.

PMID- 11571290
TI  - Proteasomal degradation of Smad1 induced by bone morphogenetic proteins.
AB  - The bone morphogenetic proteins (BMPs) regulate early embryogenesis and
      morphogenesis of multiple organs, such as bone, kidney, limbs, and muscle. Smad1
      is one of the key signal transducers of BMPs and is responsible for transducing
      receptor activation signals from the cytoplasm to the nucleus, where Smad1 serves
      as a transcriptional regulator of various BMP-responsive genes. Based upon the
      ability of Smad1 to bind multiple proteins involved in proteasome-mediated
      degradation pathway, we investigated whether Smad1 could be a substrate for
      proteasome. We found that Smad1 is targeted to proteasome for degradation in
      response to BMP type I receptor activation. The targeting of Smad1 to proteasome
      involves not only the receptor activation-induced Smad1 ubiquitination but also
      the targeting functions of the ornithine decarboxylase antizyme and the
      proteasome beta subunit HsN3. Our studies provide the first evidence for BMP
      induced proteasomal targeting and degradation of Smad1 and also reveal new
      players and novel mechanisms involved in this important aspect of Smad1
      regulation and function.

PMID- 11571291
TI  - IkappaBbeta, but not IkappaBalpha, functions as a classical cytoplasmic inhibitor
      of NF-kappaB dimers by masking both NF-kappaB nuclear localization sequences in
      resting cells.
AB  - NF-kappaB dimers, inhibitor IkappaB proteins, and NF-kappaB.IkappaB complexes
      exhibit distinct patterns in partitioning between nuclear and cytoplasmic
      cellular compartments. IkappaB-dependent modulation of NF-kappaB subcellular
      localization represents one of the more poorly understood processes in the NF
      kappaB signaling pathway. In this study, we have combined in vitro biochemical
      and cell-based methods to elucidate differences in NF-kappaB regulation exhibited
      by the inhibitors IkappaBbeta and IkappaBalpha. We show that although both
      IkappaBalpha and IkappaBbeta bind to NF-kappaB with similar global architecture
      and stability, significant differences exist that contribute to their unique
      functional roles. IkappaBbeta derives its high affinity toward NF-kappaB dimers
      by binding to both NF-kappaB subunit nuclear localization signals. In contrast,
      IkappaBalpha contacts only one NF-kappaB NLS and employs its carboxyl-terminal
      proline, glutamic acid, serine, and threonine-rich region for high affinity NF
      kappaB binding. We show that the presence of one free NLS in the NF
      kappaB.IkappaBalpha complex renders it a dynamic nucleocytoplasmic complex,
      whereas NF-kappaB.IkappaBbeta complexes are localized to the cytoplasm of resting
      cells.

PMID- 11571292
TI  - Identification of an N-cadherin motif that can interact with the fibroblast
      growth factor receptor and is required for axonal growth.
AB  - In this study, we show that the neurite outgrowth response stimulated by N
      cadherin is inhibited by a recently developed and highly specific fibroblast
      growth factor receptor (FGFR) antagonist. To test whether the N-cadherin response
      also requires FGF function, we developed peptide mimetics of the receptor binding
      sites on FGFs. Most mimetics inhibit the neurite outgrowth response stimulated by
      FGF in the absence of any effect on the N-cadherin response. The exceptions to
      this result were two mimetics of a short FGF1 sequence, which has been shown to
      interact with the region of the FGFR containing the histidine-alanine-valine
      motif. These peptides inhibited FGF and N-cadherin responses with similar
      efficacy. The histidine-alanine-valine region of the FGFR has previously been
      implicated in the N-cadherin response, and a candidate interaction site has been
      identified in extracellular domain 4 of N-cadherin. We now show that antibodies
      directed to this site on N-cadherin inhibit the neurite outgrowth response
      stimulated by N-cadherin, and peptide mimetics of the site inhibit N-cadherin and
      FGF responses. Thus, we can conclude that N-cadherin contains a novel motility
      motif in extracellular domain 4, and that peptide mimetics of this motif can
      interact with the FGFR.

PMID- 11571293
TI  - The platelet-activating factor receptor protects epidermal cells from tumor
      necrosis factor (TNF) alpha and TNF-related apoptosis-inducing ligand-induced
      apoptosis through an NF-kappa B-dependent process.
AB  - A number of chemical mediators can induce human keratinocytes and epidermal
      derived carcinomas to undergo apoptosis, or programmed cell death. Recent
      evidence suggests pro-inflammatory cytokines, such as interleukin-1 beta or
      transforming growth factor alpha, protects carcinomas from numerous pro-apoptotic
      stimuli. Platelet-activating factor (1-alkyl-2-acetyl-3-glycerophosphocholine;
      PAF) is a lipid mediator with pro-inflammatory effects on numerous cell types.
      Although PAF can be metabolized to other bioactive lipids, the majority of PAF
      effects occur through activation of a G protein-coupled receptor. Using a model
      system created by retroviral transduction of the PAF receptor (PAF-R) into the
      PAF-R-negative human epidermal cell line KB and the PAF-R-expressing keratinocyte
      cell line HaCaT, we now demonstrate that activation of the epidermal PAF-R
      results in protection from apoptosis induced by tumor necrosis factor (TNF) alpha
      or TNF-related apoptosis-inducing ligand. The PAF-mediated protection was
      inhibited by PAF-R antagonists, and protection did not occur in PAF-R-negative KB
      cells. Additionally, we show protection from TNFalpha- or TRAIL-induced apoptosis
      by PAF-R activation is dependent on the transcription factor nuclear factor (NF)
      kappa B, because PAF-R activation-induced NF-kappa B and epidermal cells
      transduced with a super-repressor form of inhibitor kappa B were not protected by
      the PAF-R. These studies provide a mechanism whereby the epidermal PAF-R, and
      possibly other G protein-coupled receptors, can exert anti-apoptotic effects
      through an NF-kappa B-dependent process.

PMID- 11571296
TI  - Analyses of p53 target genes in the human genome by bioinformatic and microarray
      approaches.
AB  - The completion of the human genome sequence (International Human Genome Sequence
      Consortium (2001) Nature 409, 860-921; Venter, J. C., et al. (2001) Science 291,
      1304-1351) allows for new ways to analyze global cellular regulatory mechanisms.
      Here we present a strategy to identify genes regulated by specific transcription
      factors in the human genome, and apply it to p53. We first collected promoters or
      introns of all genes available using two methods: GenBank(TM) annotation and a
      computationally derived transcript map. 4,852 genes analyzed in this way
      contained at least one p53 consensus binding sequence. Of 13 genes randomly
      selected for mRNA analysis, 11 were shown to respond to p53 expression. Five
      promoters were analyzed by chromatin immunoprecipitation, which revealed that all
      were bound by p53 in vivo. We then analyzed 33,615 unique human genes on cDNA
      microarrays, identifying 1,501 genes that respond to p53 expression. A parameter
      was derived that demonstrates that in silico prediction greatly enriches for
      genes that are activated and repressed by p53 and assists us to suggest other
      signaling pathways that may be connected to p53. The methods shown here
      illustrate a novel approach to analysis of global gene regulatory network through
      the integration of human genomic sequence information and genome-wide gene
      expression analysis.

PMID- 11571294
TI  - Tumor necrosis factor-alpha induces Bax-Bak interaction and apoptosis, which is
      inhibited by adenovirus E1B 19K.
AB  - Tumor necrosis factor (TNF)-alpha-mediated death signaling induces
      oligomerization of proapoptotic Bcl-2 family member Bax into a high molecular
      mass protein complex in mitochondrial membranes. Bax complex formation is
      associated with the release of cytochrome c, which propagates death signaling by
      acting as a cofactor for caspase-9 activation. The adenovirus Bcl-2 homologue E1B
      19K blocks TNF-alpha-mediated apoptosis by preventing cytochrome c release,
      caspase-9 activation, and apoptosis of virus-infected cells. TNF-alpha induces
      E1B 19K-Bax interaction and inhibits Bax oligomerization. Oligomerized Bax may
      form a pore to release mitochondrial proteins, analogous to the homologous pore
      forming domains of bacterial toxins. E1B 19K can also bind to proapoptotic Bak,
      but the functional significance is not known. TNF-alpha signaling induced Bak-Bax
      interaction and both Bak and Bax oligomerization. E1B 19K was constitutively in a
      complex with Bak, and blocked the Bak-Bax interaction and oligomerization of
      both. The TNF-alpha-mediated cytochrome c and Smac/DIABLO release from
      mitochondria was inhibited by E1B 19K expression in adenovirus-infected cells.
      Since either Bax or Bak is essential for death signaling by TNF-alpha, the
      interaction between E1B 19K and both Bak and Bax may be required to inhibit their
      cooperative or independent oligomerization to release proteins from mitochondria
      which promote caspase activation and cell death.

PMID- 11571295
TI  - Regulation of vascular endothelial growth factor expression by advanced glycation
      end products.
AB  - Advanced glycation end products (AGEs) are generated during long term diabetes
      and are correlated with the development of diabetic complications, such as
      retinopathy. Diabetic retinopathy is characterized by an increased retinal
      neovascularization due to the action of the angiogenic factor, vascular
      endothelial growth factor (VEGF). In this report, we show that injection of
      insulin and glycated albumin (Alb-AGE) to mice increases VEGF mRNA expression in
      eyes. Insulin and Alb-AGE stimulate VEGF mRNA and protein expression in retinal
      epithelial cells (ARPE-19). Alb-AGE-induced VEGF expression is not modulated by
      the use of antioxidants, N-acetyl-l-cysteine or pyrrolidinedithiocarbamate, or by
      an inhibitor of phosphatidylinositol 3-kinase (PI3K), wortmannin. However, using
      an inhibitor of ERK activation, U0126, we show that Alb-AGE stimulates VEGF
      expression through an ERK-dependent pathway. Accordingly, we found that Alb-AGE
      activated mitogen-activate protein kinase, ERK1/2, JNK1/2, but not p38, and that
      Alb-AGE did not activate PI3K and PKB. Moreover, Alb-AGE activated the
      transcription factor, hypoxia inducible factor-1 (HIF-1) DNA binding activity.
      This activation is mediated by an increase in accumulation of the HIF-1alpha
      protein through an ERK-dependent pathway. Thus, stimulation of VEGF expression by
      Alb-AGE, through the activation of HIF-1, could play an important role in the
      development of diabetic retinopathy.

PMID- 11571298
TI  - Expression of functional chemokine receptors CXCR3 and CXCR4 on human melanoma
      cells.
AB  - Chemokines are secreted into the tumor microenvironment by tumor-infiltrating
      inflammatory cells as well as by tumor cells. Chemokine receptors mediate agonist
      dependent cell responses, including migration and activation of several signaling
      pathways. In the present study we show that several human melanoma cell lines and
      melanoma cells on macroscopically infiltrated lymph nodes express the chemokine
      receptors CXCR3 and CXCR4. Using the highly invasive melanoma cell line BLM, we
      demonstrate that the chemokine Mig, a ligand for CXCR3, activates the small
      GTPases RhoA and Rac1, induces a reorganization of the actin cytoskeleton, and
      triggers cell chemotaxis and modulation of integrin VLA-5- and VLA-4-dependent
      cell adhesion to fibronectin. Furthermore, the chemokine SDF-1alpha, the ligand
      of CXCR4, triggered modulation of beta(1) integrin-dependent melanoma cell
      adhesion to fibronectin. Additionally, Mig and SDF-1alpha activated MAPKs p44/42
      and p38 on melanoma cells. Expression of functional CXCR3 and CXCR4 receptors on
      melanoma cells indicates that they might contribute to cell motility during
      invasion as well as to regulation of cell proliferation and survival.

PMID- 11571297
TI  - Hepatocyte growth factor/scatter factor blocks the mitochondrial pathway of
      apoptosis signaling in breast cancer cells.
AB  - The cytokine hepatocyte growth factor/scatter factor (HGF/SF) has been found to
      protect a variety of epithelial and cancer cell types against cytotoxicity and
      apoptosis induced by DNA damage, but the specific apoptotic signaling events and
      the levels at which they are blocked by HGF/SF have not been identified. We found
      that treatment of MDA-MB-453 human breast cancer cells with adriamycin (also
      known as doxorubicin, a DNA topoisomerase IIalpha inhibitor) induced a series of
      time-dependent events, including the mitochondrial release of cytochrome c and
      apoptosis-inducing factor, mitochondrial membrane depolarization, activation of a
      set of caspases (caspase-9, -3, -7, -2, and -8), cleavage of poly(ADP-ribose)
      polymerase (PARP), and up-regulation of expression of the Fas ligand. All of
      these events were blocked by preincubation of the cells with HGF/SF. In contrast,
      the pan-caspase inhibitor benzyloxycarbonyl-VAD-fluoromethylketone blocked some
      of these events (e.g. caspase-3 activation and PARP cleavage) but did not block
      cytochrome c release or mitochondrial depolarization. These findings suggest that
      HGF/SF functions, in part, upstream of the mitochondria to block mitochondrial
      apoptosis signaling, prevent activation of multiple caspases, and protect breast
      cancer cells against apoptosis.

PMID- 11571299
TI  - Pus1p-dependent tRNA pseudouridinylation becomes essential when tRNA biogenesis
      is compromised in yeast.
AB  - Yeast Pus1p catalyzes the formation of pseudouridine (psi) at specific sites of
      several tRNAs, but its function is not essential for cell viability. We show here
      that Pus1p becomes essential when another tRNA:pseudouridine synthase, Pus4p, or
      the essential minor tRNA for glutamine are mutated. Strikingly, this mutant tRNA,
      which carries a mismatch in the T psi C arm, displays a nuclear export defect.
      Furthermore, nuclear export of at least one wild-type tRNA species becomes
      defective in the absence of Pus1p. Our data, thus, show that the modifications
      formed by Pus1p are essential when other aspects of tRNA biogenesis or function
      are compromised and suggest that impairment of nuclear tRNA export in the absence
      of Pus1p might contribute to this phenotype.

PMID- 11571300
TI  - Tumor necrosis factor-alpha-converting enzyme mediates the inducible cleavage of
      fractalkine.
AB  - Fractalkine (FK, CX3CL1) is a novel multidomain protein expressed on the surface
      of endothelial cells. As a full-length transmembrane protein, FK binds cells
      expressing CX3CR1, its cognate receptor, with high affinity. Proteolytic cleavage
      of FK releases a soluble form that is a potent chemoattractant for monocytes, T
      cells, and natural killer cells. Activation of protein kinase C dramatically
      increases the rate of this cleavage. Regulation of FK cleavage is critical for
      maintaining the balance between the immobilized and soluble forms, but the
      protease responsible has not been identified. Here we report that tumor necrosis
      factor-alpha-converting enzyme (TACE) is primarily responsible for the inducible
      cleavage of FK. After transfection into host cells, the proteolytic cleavage of
      FK was blocked by TACE-specific inhibitors and was not detected in cells
      genetically altered to remove TACE activity. In contrast, the constitutive
      cleavage of FK was not mediated by TACE and proceeded normally in TACE-null
      fibroblasts. We conclude that TACE is primarily responsible for the inducible
      cleavage of FK. These studies identify a potentially important link between local
      generation of potent cytokines and control of the balance between the cell
      adhesion and chemotactic properties of FK.

PMID- 11571301
TI  - A three-dimensional model of the human facilitative glucose transporter Glut1.
AB  - The human facilitative transporter Glut1 is the major glucose transporter present
      in all human cells, has a central role in metabolism, and is an archetype of the
      superfamily of major protein facilitators. Here we describe a three-dimensional
      structure of Glut1 based on helical packing schemes proposed for lactose permease
      and Glut1 and predictions of secondary structure, and refined using energy
      minimization, molecular dynamics simulations, and quality and environmental
      scores. The Ramachandran scores and the stereochemical quality of the structure
      obtained were as good as those for the known structures of the KcsA K(+) channel
      and aquaporin 1. We found two channels in Glut1. One of them traverses the
      structure completely, and is lined by many residues known to be solvent
      accessible. Since it is delimited by the QLS motif and by several well conserved
      residues, it may serve as the substrate transport pathway. To validate our
      structure, we determined the distance between these channels and all the residues
      for which mutations are known. From the locations of sugar transporter
      signatures, motifs, and residues important to the transport function, we find
      that this Glut1 structure is consistent with mutagenesis and biochemical studies.
      It also accounts for functional deficits in seven pathogenic mutants.

PMID- 11571302
TI  - Similar turnover and shedding of the cellular prion protein in primary lymphoid
      and neuronal cells.
AB  - The cellular prion protein (PrP(C)) is essential for pathogenesis and
      transmission of prion diseases. Although prion replication in the brain is
      accompanied by neurodegeneration, prions multiply efficiently in the
      lymphoreticular system without any detectable pathology. We have used pulse-chase
      metabolic radiolabeling experiments to investigate the turnover and processing of
      PrP(C) in primary cell cultures derived from lymphoid and nervous tissues.
      Similar kinetics of PrP(C) degradation were observed in these tissues. This
      indicates that the differences between these two organs with respect to their
      capacity to replicate prions is not due to differences in the turnover of PrP(C).
      Substantial amounts of a soluble form of PrP that lacks the glycolipid anchor
      appeared in the medium of splenocytes and cerebellar granule cells. Soluble PrP
      was detected in murine and human serum, suggesting that it might be of
      physiological relevance.

PMID- 11571303
TI  - Mutagenesis of apobec-1 complementation factor reveals distinct domains that
      modulate RNA binding, protein-protein interaction with apobec-1, and
      complementation of C to U RNA-editing activity.
AB  - C to U editing of apolipoprotein B (apoB) RNA requires a multicomponent
      holoenzyme complex in which minimal constituents include apobec-1 and apobec-1
      complementation factor (ACF). We have examined the predicted functional domains
      in ACF in binding apoB RNA, interaction with apobec-1, and complementation of RNA
      editing. We demonstrate that apoB RNA binding and apobec-1-interacting domains
      are defined by two partially overlapping regions containing the NH(2)-terminal
      RNA recognition motifs of ACF. Both apoB RNA binding and apobec-1 interaction are
      required for editing complementation activity. ACF is a nuclear protein that upon
      cotransfection with apobec-1 results in nuclear colocalization and redistribution
      of apobec-1 from the cytoplasm. ACF constructs with deletions or mutations in the
      putative nuclear localization signal (NLS) still localize in the nucleus of
      transfected cells but do not colocalize with apobec-1, the latter remaining
      predominantly cytoplasmic. These observations suggest that the putative NLS motif
      in ACF is not responsible for its nucleo-cytoplasmic trafficking. By contrast,
      protein-protein interaction is important for the nuclear import of apobec-1.
      Taken together, these data suggest that functional complementation of C to U RNA
      editing by apobec-1 involves the NH(2)-terminal 380 residues of ACF.

PMID- 11571304
TI  - Matrix metalloproteinase activity inactivates the CXC chemokine stromal cell
      derived factor-1.
AB  - Chemokines provide directional cues for leukocyte migration and activation that
      are essential for normal leukocytic trafficking and for host responses during
      processes such as inflammation, infection, and cancer. Recently we reported that
      matrix metalloproteinases (MMPs) modulate the activity of the CC chemokine
      monocyte chemoattractant protein-3 by selective proteolysis to release the N
      terminal tetrapeptide. Here we report the N-terminal processing, also at position
      4-5, of the CXC chemokines stromal cell-derived factor (SDF)-1alpha and beta by
      MMP-2 (gelatinase A). Robustness of the MMP family for chemokine cleavage was
      revealed from identical cleavage site specificity of MMPs 1, 3, 9, 13, and 14
      (MT1-MMP) toward SDF-1; selectivity was indicated by absence of cleavage by MMPs
      7 and 8. Efficient cleavage of SDF-1alpha by MMP-2 is the result of a strong
      interaction with the MMP hemopexin C domain at an exosite that overlaps the
      monocyte chemoattractant protein-3 binding site. The association of SDF-1alpha
      with different glycosaminoglycans did not inhibit cleavage. MMP cleavage of SDF
      1alpha resulted in loss of binding to its cognate receptor CXCR-4. This was
      reflected in a loss of chemoattractant activity for CD34(+) hematopoietic
      progenitor stem cells and pre-B cells, and unlike full-length SDF-1alpha, the MMP
      cleaved chemokine was unable to block CXCR-4-dependent human immunodeficiency
      virus-1 infection of CD4(+) cells. These data suggest that MMPs may be important
      regulatory proteases in attenuating SDF-1 function and point to a deep
      convergence of two important networks, chemokines and MMPs, to regulate
      leukocytic activity in vivo.

PMID- 11571305
TI  - Interaction of the alpha-subunit of Escherichia coli RNA polymerase with DNA:
      rigid body nature of the protein-DNA contact.
AB  - The alpha-subunit of Escherichia coli RNA polymerase plays an important role in
      the activity of many promoters by providing a direct protein-DNA contact with a
      specific sequence (UP element) located upstream of the core promoter sequence. To
      obtain insight into the nature of thermodynamic forces involved in the formation
      of this protein-DNA contact, the binding of the alpha-subunit of E. coli RNA
      polymerase to a fluorochrome-labeled DNA fragment containing the rrnB P1 promoter
      UP element sequence was quantitatively studied using fluorescence polarization.
      The alpha dimer and DNA formed a 1:1 complex in solution. Complex formation at 25
      degrees C was enthalpy-driven, the binding was accompanied by a net release of 1
      2 ions, and no significant specific ion effects were observed. The van't Hoff
      plot of temperature dependence of binding was linear suggesting that the heat
      capacity change (Deltac(p)) was close to zero. Protein footprinting with
      hydroxyradicals showed that the protein did not change its conformation upon
      protein-DNA contact formation. No conformational changes in the DNA molecule were
      detected by CD spectroscopy upon protein-DNA complex formation. The thermodynamic
      characteristics of the binding together with the lack of significant
      conformational changes in the protein and in the DNA suggested that the alpha
      subunit formed a rigid body-like contact with the DNA in which a tight
      complementary recognition interface between alpha-subunit and DNA was not formed.

PMID- 11571306
TI  - Cholesterol overload promotes morphogenesis of a Niemann-Pick C (NPC)-like
      compartment independent of inhibition of NPC1 or HE1/NPC2 function.
AB  - Cholesterol accumulation in an aberrant endosomal/lysosomal compartment is the
      hallmark of Niemann-Pick type C (NPC) disease. To gain insight into the etiology
      of the NPC compartment, we studied a novel Chinese hamster ovary cell mutant that
      was identified through a genetic screen and phenocopies the NPC1 mutation. We
      show that the M87 mutant harbors a mutation in a gene distinct from the NPC1 and
      HE1/NPC2 disease genes. M87 cells have increased total cellular cholesterol with
      accumulation in an aberrant compartment that contains LAMP-1, LAMP-2, and NPC1,
      but not CI-MPR, similar to the cholesterol-rich compartment in NPC mutant cells.
      We demonstrate that low-density lipoprotein receptor activity is increased 3-fold
      in the M87 mutant, and likely contributes to accumulation of excess cholesterol.
      In contrast to NPC1-null cells, the M87 mutant exhibits normal rates of delivery
      of endosomal cholesterol to the endoplasmic reticulum and to the plasma membrane.
      The preserved late endosomal function in the M87 mutant is associated with the
      presence of NPC1-containing multivesicular late endosomes and supports a role for
      these multivesicular late endosomes in the sorting and distribution of
      cholesterol. Our findings implicate cholesterol overload in the formation of an
      NPC-like compartment that is independent of inhibition of NPC1 or HE1/NPC2
      function.

PMID- 11571307
TI  - Transcription factor FoxA (HNF3) on a nucleosome at an enhancer complex in liver
      chromatin.
AB  - Nucleosome-like particles and acetylated histones occur near active promoters and
      enhancers, and certain transcription factors can recognize their target sites on
      the surface of a nucleosome in vitro; yet it has been unclear whether
      transcription factors can occupy target sites on nucleosomes in native chromatin.
      We developed a method for sequential chromatin immunoprecipitation of distinct
      nuclear proteins that are simultaneously cross-linked to nucleosome-sized genomic
      DNA segments. We find that core histone H2A co-occupies, along with the FoxA
      (hepatocyte nuclear factor-3) transcription factor, DNA for the albumin
      transcriptional enhancer in native liver chromatin, where the enhancer is active.
      Because histone H2A on nuclear DNA is only known to exist in nucleosomes, we
      conclude that transcription factors can form a stable complex on nucleosomes at
      an active enhancer element in vivo.

PMID- 11571308
TI  - Tumor necrosis factor-alpha regulates the expression of inducible costimulator
      receptor ligand on CD34(+) progenitor cells during differentiation into antigen
      presenting cells.
AB  - The inducible costimulator receptor (ICOS) is a third member of the CD28 receptor
      family that regulates T cell activation and function. ICOS binds to a newly
      identified ligand on antigen presenting cells different from the CD152 ligands
      CD80 and CD86. We used soluble ICOSIg and a newly developed murine anti-human
      ICOS ligand (ICOSL) monoclonal antibody to further characterize the ICOSL during
      ontogeny of antigen presenting cells. In a previous study, we found that ICOSL is
      expressed on monocytes, dendritic cells, and B cells. To define when ICOSL is
      first expressed on myeloid antigen presenting cells, we examined ICOSL expression
      on CD34(+) cells in bone marrow. We found that CD34(bright) cells regardless of
      their myeloid commitment were ICOSL(-), whereas ICOSL was first expressed when
      CD34 expression diminished and the myeloid marker CD33 appeared. However, acute
      myeloid leukemia cells were ICOSL-negative, whereas among B-cell malignancies
      only some cases of the most mature tumors such as prolymphocytic leukemia and
      hairy cell leukemia were positive. Next, we investigated purified CD34(+)
      hematopoietic progenitor cells that did not constitutively express ICOSL but were
      induced to express ICOSL within 12 h after granulocyte/macrophage colony
      stimulating factor/tumor necrosis factor alpha (TNF-alpha) stimulation.
      Interestingly, ICOSL was induced prior to CD80/CD86 induction on CD34(+) cells so
      that ICOSL was expressed in the absence of CD80/CD86. This suggests that ICOSL is
      an early differentiation marker along the monocytic/dendritic maturation pathway.
      Induction of ICOSL was dependent on TNF-alpha and was regulated via NF-kappa B as
      revealed by use of inhibitors specific for I kappa B alpha phosphorylation such
      as BAY 11-7082 and BAY 11-7085. The antigen presenting capacity of TNF-alpha
      stimulated CD34(+) cells was strongly inhibited by ICOSIg fusion proteins or by
      NF-kappa B inhibition. Thus, TNF-alpha-induced ICOSL expression seemed to be
      functionally important for the costimulatory capacity of CD34(+) hematopoietic
      progenitor cells.

PMID- 11571309
TI  - Regulation of epithelial sodium channel activity through a region of the carboxyl
      terminus of the alpha -subunit. Evidence for intracellular kinase-mediated
      reactions.
AB  - The epithelial sodium channel (ENaC) is a heteromultimer composed of three
      subunits, each having two membrane-spanning domains with intracellular amino and
      carboxyl termini. Several hormones and proteins regulate channel activity, but
      the molecular nature of this regulation is unknown. We conducted experiments to
      determine a possible new site within the carboxyl terminus of the alpha-subunit
      involved in enhanced channel activity through endogenous kinases. When an alpha
      subunit that was truncated to remove a PY motif was expressed in Xenopus oocytes
      with wild type human beta- and gamma-ENaC subunits, channel activity was greatly
      enhanced. The removal of the entire intracellular carboxyl terminus of the alpha
      subunit eliminated this enhanced basal activity. Using several point mutations,
      we localized this site to two amino acid residues (Pro(595)-Gly(596)) near the
      second membrane-spanning domain. The nonspecific kinase inhibitor staurosporine
      inhibits basal channel activity of wild type ENaC but was ineffective in
      inhibiting channels mutated at this site. The major effect of these mutations was
      not on channel kinetics but was largely, if not entirely, on the number of active
      channels on the cell surface. This region is potentially important in effecting
      kinase-mediated increases in ENaC activity.

PMID- 11571311
TI  - A role for cofilin and LIM kinase in Listeria-induced phagocytosis.
AB  - The pathogenic bacterium Listeria monocytogenes is able to invade nonphagocytic
      cells, an essential feature for its pathogenicity. This induced phagocytosis
      process requires tightly regulated steps of actin polymerization and
      depolymerization. Here, we investigated how interactions of the invasion protein
      InlB with mammalian cells control the cytoskeleton during Listeria
      internalization. By fluorescence microscopy and transfection experiments, we show
      that the actin-nucleating Arp2/3 complex, the GTPase Rac, LIM kinase (LIMK), and
      cofilin are key proteins in InlB-induced phagocytosis. Overexpression of LIMK1,
      which has been shown to phosphorylate and inactivate cofilin, induces
      accumulation of F-actin beneath entering particles and inhibits internalization.
      Conversely, inhibition of LIMK's activity by expressing a dominant negative
      construct, LIMK1(-), or expression of the constitutively active S3A cofilin
      mutant induces loss of actin filaments at the phagocytic cup and also inhibits
      phagocytosis. Interestingly, those constructs similarly affect other actin-based
      phenomenons, such as InlB-induced membrane ruffling or Listeria comet tail
      formations. Thus, our data provide evidence for a control of phagocytosis by both
      activation and deactivation of cofilin. We propose a model in which cofilin is
      involved in the formation and disruption of the phagocytic cup as a result of its
      local progressive enrichment.

PMID- 11571310
TI  - Dense core secretory vesicles revealed as a dynamic Ca(2+) store in
      neuroendocrine cells with a vesicle-associated membrane protein aequorin
      chimaera.
AB  - The role of dense core secretory vesicles in the control of cytosolic-free Ca(2+)
      concentrations ([Ca(2+)](c)) in neuronal and neuroendocrine cells is enigmatic.
      By constructing a vesicle-associated membrane protein 2-synaptobrevin.aequorin
      chimera, we show that in clonal pancreatic islet beta-cells: (a) increases in
      [Ca(2+)](c) cause a prompt increase in intravesicular-free Ca(2+) concentration
      ([Ca(2+)]SV), which is mediated by a P-type Ca(2+)-ATPase distinct from the
      sarco(endo) plasmic reticulum Ca(2+)-ATPase, but which may be related to the
      PMR1/ATP2C1 family of Ca(2+) pumps; (b) steady state Ca(2+) concentrations are 3
      5-fold lower in secretory vesicles than in the endoplasmic reticulum (ER) or
      Golgi apparatus, suggesting the existence of tightly bound and more rapidly
      exchanging pools of Ca(2+); (c) inositol (1,4,5) trisphosphate has no impact on
      [Ca(2+)](SV) in intact or permeabilized cells; and (d) ryanodine receptor (RyR)
      activation with caffeine or 4-chloro-3-ethylphenol in intact cells, or cyclic
      ADPribose in permeabilized cells, causes a dramatic fall in [Ca(2+)](SV). Thus,
      secretory vesicles represent a dynamic Ca(2+) store in neuroendocrine cells,
      whose characteristics are in part distinct from the ER/Golgi apparatus. The
      presence of RyRs on secretory vesicles suggests that local Ca(2+)-induced Ca(2+)
      release from vesicles docked at the plasma membrane could participate in
      triggering exocytosis.

PMID- 11571313
TI  - Models of progression in AD: predicting disability and costs.

PMID- 11571314
TI  - Does viral disease underlie ALS? Lessons from the AIDS pandemic.

PMID- 11571312
TI  - In vivo requirement of the alpha-syntrophin PDZ domain for the sarcolemmal
      localization of nNOS and aquaporin-4.
AB  - alpha-Syntrophin is a scaffolding adapter protein expressed primarily on the
      sarcolemma of skeletal muscle. The COOH-terminal half of alpha-syntrophin binds
      to dystrophin and related proteins, leaving the PSD-95, discs-large, ZO-1 (PDZ)
      domain free to recruit other proteins to the dystrophin complex. We investigated
      the function of the PDZ domain of alpha-syntrophin in vivo by generating
      transgenic mouse lines expressing full-length alpha-syntrophin or a mutated alpha
      syntrophin lacking the PDZ domain (Delta PDZ). The Delta PDZ alpha-syntrophin
      displaced endogenous alpha- and beta 1-syntrophin from the sarcolemma and
      resulted in sarcolemma containing little or no syntrophin PDZ domain. As a
      consequence, neuronal nitric oxide synthase (nNOS) and aquaporin-4 were absent
      from the sarcolemma. However, the sarcolemmal expression and distribution of
      muscle sodium channels, which bind the alpha-syntrophin PDZ domain in vitro, were
      not altered. Both transgenic mouse lines were bred with an alpha-syntrophin-null
      mouse which lacks sarcolemmal nNOS and aquaporin-4. The full-length alpha
      syntrophin, not the Delta PDZ form, reestablished nNOS and aquaporin-4 at the
      sarcolemma of these mice. Genetic crosses with the mdx mouse showed that neither
      transgenic syntrophin could associate with the sarcolemma in the absence of
      dystrophin. Together, these data show that the sarcolemmal localization of nNOS
      and aquaporin-4 in vivo depends on the presence of a dystrophin-bound alpha
      syntrophin PDZ domain.

PMID- 11571316
TI  - Marked increase in cyclooxygenase-2 in ALS spinal cord: implications for therapy.
AB  - OBJECTIVE: To evaluate the hypothesis that cyclooxygenase-2 (COX-2) is linked to
      the pathology of ALS by determining whether COX-2 mRNA levels are upregulated in
      ALS spinal cord. METHODS: Spinal cord from 11 ALS cases and 27 controls
      consisting of 15 cases of Alzheimer disease (AD), six cases of Parkinson disease
      (PD), three cases of cerebrovascular disease, and three control cases were
      analyzed. Total RNA was extracted and reverse transcriptase-PCR analysis
      performed for the mRNA of COX-2, COX-1, the microglial marker CD11b, and the
      housekeeping gene cyclophilin. RESULTS: In ALS compared with non-ALS spinal cord,
      COX-2 mRNA was upregulated 7.09-fold (p < 0.0001), COX-1 1.14-fold (p = 0.05),
      and CD11b 1.85-fold (p = 0.0012). COX-2 mRNA levels in AD, PD, cerebrovascular
      disease, and control cases were each significantly lower than in ALS and were not
      significantly different from each other. Western blots of the protein products
      were in general accord with the mRNA data, with COX-2 protein levels being
      upregulated 3.79-fold compared with non-ALS cases (p = 0.015). CONCLUSIONS: The
      strong upregulation of COX-2 mRNA in ALS is in accord with studies in the
      superoxide dismutase transgenic mouse model in which COX-2 upregulation occurs.
      Taken in conjunction with evidence of a neuroprotective effect of COX-2
      inhibitors in certain animal models and in organotypic cultures, the data are
      supportive of a possible future role for COX-2 inhibitors in the treatment of
      ALS.

PMID- 11571317
TI  - Measuring Alzheimer's disease progression with transition probabilities:
      estimates from CERAD.
AB  - OBJECTIVES: To estimate annual transition probabilities (i.e., the likelihood
      that a patient will move from one disease stage to another in a given time
      period) for AD progression. Transition probabilities are estimated by disease
      stages (mild, moderate, severe) and settings of care (community, nursing home),
      accounting for differences in age, gender, and behavioral symptoms as well as the
      length of time a patient has been in a disease stage. METHODS: Using data from
      the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the
      authors employed a modified survival analysis to estimate stage-to-stage and
      stage-to-nursing home transition probabilities. To account for individual
      variability, a Cox proportional hazards model was fit to the CERAD data to
      estimate hazard ratios for gender, age (50 to 64, 65 to 74, and more than 75
      years), and level of behavioral symptoms (low/high, according to responses to the
      Behavioral Rating Scale for Dementia) for each of the key stage-to-stage and
      stage-to-nursing home transitions. RESULTS: The transition probabilities
      underscore the rapid progression of patients into more severe disease stages and
      into nursing homes and the differences among population subgroups. In general,
      male gender, age under 65, and high level of behavioral symptoms were associated
      with higher transition probabilities to more severe disease stages. Disease
      progression is roughly constant as a function of the time a patient has spent in
      a particular stage. CONCLUSIONS: Transition probabilities provide a useful means
      of characterizing AD progression. Economic models of interventions for AD should
      consider the varied course of progression for different population subgroups,
      particularly those defined by high levels of behavioral symptoms.

PMID- 11571318
TI  - Assessment of health economics in Alzheimer's disease (AHEAD) based on need for
      full-time care.
AB  - OBJECTIVE: To develop a framework for estimating the long-term health and
      economic consequences of AD based on patient characteristics at a given point in
      time. METHODS: A pharmacoeconomic model (Assessment of Health Economics in
      Alzheimer's Disease, AHEAD) was developed based on equations that relate the
      probability of needing full-time care (FTC) over time to patient characteristics
      summarized in index scores. These equations were developed from published data on
      interquartile times until FTC is needed and until death, using nonlinear
      regressions of the resulting index-specific hazards. These equations were then
      incorporated into a hidden Markov framework that allows for calculation of
      expected time to FTC and to death, as well as of the economic consequences of
      disease progression. There are three major states in the model: not requiring FTC
      ("pre-FTC"), requiring FTC, and death. RESULTS: Outcomes for five sample patients
      are derived to illustrate application of the AHEAD model. The impact of altering
      disease markers in these patients is also considered. CONCLUSION: The need for a
      generally applicable tool to forecast long-term outcomes based on relatively
      short-term data is becoming increasingly acute with the advent of new therapies
      for AD. The AHEAD model provides a relatively simple framework for the prediction
      of time to FTC requirement based on short-term observed data such as those from
      clinical trials. Although subject to the uncertainties inherent in modeling, the
      model nevertheless provides a standard estimation technique that may facilitate
      comparisons between existing and emerging therapies.

PMID- 11571319
TI  - Assessment of health economics in Alzheimer's disease (AHEAD): galantamine
      treatment in Canada.
AB  - BACKGROUND: Given the high costs of caring for patients with AD in Canada, it is
      important to evaluate the costs of new therapies that halt or delay the
      advancement of AD, relative to the savings associated with delaying disease
      progression. METHODS: The Assessment of Health Economics in Alzheimer's Disease
      (AHEAD) model, which uses algorithms to predict the time until patients with AD
      require full-time care (FTC), was adapted to Canada to compare treatment with
      galantamine versus no pharmacologic treatment. Data from two clinical trials
      provided inputs into the algorithms, and forecasts were made for up to 10 years.
      Drug and health care costs were evaluated according to the stage of disease based
      on Quebec unit costs along with follow-up data from the Canadian Study of Health
      and Aging. RESULTS: Galantamine is predicted to reduce the duration of FTC by
      almost 10%. Approximately 5.6 patients with mild to moderate disease must be
      placed on treatment to avoid one year of FTC, resulting in savings averaging $788
      CAD ($528 USD) per patient. For patients with moderate disease, 3.9 patients must
      be placed on treatment to avoid one year of FTC, with savings predicted at $3718
      CAD ($2533 USD) per patient. CONCLUSION: Galantamine cannot only potentially
      increase the time before patients require FTC, but may also lead to overall
      savings because treatment costs are offset by reductions in other health care
      expenditures.

PMID- 11571320
TI  - Specificity of the fivefold increase in AD in mothers of adults with Down
      syndrome.
AB  - BACKGROUND: In a previous study, the authors found that the risk of AD among
      mothers who were 35 years or younger when their children with Down syndrome (DS)
      were born was five times that of mothers of children with other forms of mental
      retardation. The current study investigated the specificity of the familial
      aggregation of DS and AD by examining whether mothers who gave birth to children
      with DS before age 35 are also at increased risk of other age-related neurologic
      or medical disorders. METHODS: The authors used survival methods to compare
      cumulative incidence and relative risk of AD, other dementias, and common age
      related disorders in parents of 200 adults with DS and parents of 252 adults with
      other forms of mental retardation. RESULTS: Mothers who were < or =35 years of
      age when their children with DS were born were four to five times as likely to
      develop AD as control mothers (rate ratio = 4.8, 95% CI 2.1, 11.2), whereas risk
      of AD among mothers who were >35 years when their children with DS were born was
      not significantly increased (rate ratio = 1.8, 95% CI 0.6, 5.1). Risk of AD among
      fathers of probands with DS was similar to that of control fathers, and did not
      vary by age at proband birth. Risk of other dementias and of other age-related
      medical condition was similar among mothers and fathers of probands with DS and
      control parents, regardless of age at proband birth. CONCLUSION: These findings
      suggest that the increased risk of AD among mothers who gave birth to children
      with DS before age 35 appears to represent a specific vulnerability to AD, as
      opposed to other age-related degenerative disorders.

PMID- 11571321
TI  - Incidence of Alzheimer's disease in a rural community in India: the Indo-US
      study.
AB  - OBJECTIVE: To determine overall and age-specific incidence rates of AD in a
      rural, population-based cohort in Ballabgarh, India, and to compare them with
      those of a reference US population in the Monongahela Valley of Pennsylvania.
      METHODS: A 2-year, prospective, epidemiologic study of subjects aged > or =55
      years utilizing repeated cognitive and functional ability screening, followed by
      standardized clinical evaluation using the Diagnostic and Statistical Manual of
      Mental Disorders, 4th edition, and the National Institute of Neurological and
      Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders
      Association criteria for the diagnosis, and the Clinical Dementia Rating scale
      for the staging, of dementia and AD. RESULTS: Incidence rates per 1000 person
      years for AD with CDR > or =0.5 were 3.24 (95% CI: 1.48-6.14) for those aged > or
      =65 years and 1.74 (95% CI: 0.84-3.20) for those aged > or =55 years.
      Standardized against the age distribution of the 1990 US Census, the overall
      incidence rate in those aged > or =65 years was 4.7 per 1000 person-years,
      substantially lower than the corresponding rate of 17.5 per 1000 person-years in
      the Monongahela Valley. CONCLUSION: These are the first AD incidence rates to be
      reported from the Indian subcontinent, and they appear to be among the lowest
      ever reported. However, the relatively short duration of follow-up, cultural
      factors, and other potential confounders suggest caution in interpreting this
      finding.

PMID- 11571322
TI  - A prospective study of cerebral white matter abnormalities in older people with
      gait dysfunction.
AB  - OBJECTIVES: The authors previously reported cross-sectional data suggesting a
      relationship between cerebral white matter hyperintensities (WMH) and gait and
      balance dysfunction in older people. There have been no longitudinal MRI studies
      to address this issue. The current study compared progression of WMH in subjects
      with gait and balance dysfunction with that in healthy subjects. METHODS: Two
      brain MRI were performed on 70 healthy, ambulatory subjects (mean baseline age
      79, range 74 to 88) with no identifiable neurologic disease. The mean time
      between MRI was 4 years. Gait and balance were quantified using the Tinetti
      Balance and Mobility Scale, and falls were documented each year. On T2-weighted
      MRI, total hyperintense volume (HV) within three periventricular levels was
      estimated using the Cavalieri principle, and WMH were graded (0 to 4) using an
      established semiquantitative scale. RESULTS: Compared with those with normal gait
      and balance, subjects whose Tinetti scores dropped markedly (> 4 points) between
      first and second MRI showed a significantly greater mean increase in HV during
      follow-up. The larger group of subjects with an abnormal Tinetti score (< 24) at
      the time of second MRI showed a significantly greater mean increase in HV,
      compared with those with normal gait and balance at follow-up. Subjects with
      marked WMH at baseline showed significantly greater increase in HV over time.
      Subjects with abnormal Tinetti scores had significantly more falls than subjects
      with normal Tinetti scores. CONCLUSIONS: Some older people develop gait and
      balance dysfunction that is associated with gradual onset of cerebral white
      matter disease.

PMID- 11571323
TI  - Reversible ALS-like disorder in HIV infection.
AB  - OBJECTIVE: To describe the clinical features, treatment, and outcome of six cases
      of HIV-1-associated ALS-like disorder. METHODS: The authors reviewed patients
      with HIV infection with neurologic symptoms seen over a 13-year period. Patients
      were identified by using the El Escorial research diagnostic criteria defining
      three categories of certainty for definite, probable, or possible ALS. Clinical
      features, EMG, CSF, serum analyses, and imaging and virological studies were
      assessed. RESULTS: Six patients with immunodepression (mean CD4(+) cells =
      86.2/mm(3); mean age = 34 years) developed distal motor weakness mimicking a
      monomelic amyotrophy that subacutely progressed regionally or assumed a symmetric
      distribution on more than one region. EMG was characteristic of motor neuron
      disease with no multifocal conduction block. Causes other than HIV-1 were ruled
      out. The unusual rapid extension of the disease and the positive response to
      antiretroviral therapy suggest that ALS syndrome and HIV infection are
      etiologically related. HIV-1 might cause an ALS-like disorder by several
      mechanisms-via neuronal infection, by secretion of toxic viral substance, by
      inducing the immune system to secrete cytokines, or by inducing an autoimmune
      disease. CONCLUSION: These cases suggest that the association between some motor
      neuron diseases and HIV infection is not coincidental but pathogenetically
      related and that ALS-like disorder should be considered an HIV-related neurologic
      complication.

PMID- 11571324
TI  - Neural correlates of attention and working memory deficits in HIV patients.
AB  - OBJECTIVES: To evaluate the neural correlates of attention and working memory
      deficits in patients with HIV-1. METHOD: fMRI was used to evaluate brain activity
      in 11 patients with HIV and 11 age-, sex-, education-, and handedness-matched
      seronegative subjects, while performing a battery of tasks that required
      different levels of attention for working memory. RESULTS: Patients with HIV
      showed greater brain activation (blood oxygenation level dependent signal
      changes) in some regions compared with control subjects while performing the same
      tasks. For the simpler tasks, patients with HIV showed greater activation in the
      parietal regions. However, with more difficult tasks, patients with HIV showed
      greater activation additionally in the frontal lobes. Reaction times during these
      tasks were slower but accuracy was similar in the patients with HIV compared with
      control subjects. CONCLUSION: Injury to the neural substrate caused by HIV
      infection may necessitate greater attentional modulation of the neural circuits,
      hence a greater use of the brain reserve; additional activation of the frontal
      lobes is required to perform the more complex tasks. The task-dependent increased
      frontal activation in patients with HIV suggests that the neural correlate of
      attentional deficits may be excessive attentional modulation as a result of
      frontostriatal brain injury.

PMID- 11571325
TI  - Chronic ischemic monomelic neuropathy from critical limb ischemia.
AB  - OBJECTIVE: To describe the peripheral neuropathy resulting from chronic and
      critical arterial leg ischemia. METHODS: The authors evaluated 19 patients on
      entry to a gene therapy treatment trial for chronic and critical leg ischemia.
      Measurements included medical history, examination, neurologic symptom (NSS) and
      neurologic examination (NES) scores, motor and sensory nerve conduction studies,
      and quantitative sensory testing. The critically ischemic leg was compared with
      the less affected contralateral limb. RESULTS: All patients experienced pain from
      skin ulceration or vascular claudication, but many also had rest pain (58%),
      numbness (58%), burning (42%), and paresthesias (37%) in the ischemic foot that
      were consistent with peripheral nerve ischemia. Only three patients (16%) were
      free of neuropathic symptoms. The most common asymmetric neurologic signs
      included hypalgesia (74%), toe weakness (64%), hyperesthesia (63%), and
      pallanesthesia (53%) in the distal leg. NSS and NES were more abnormal in the
      critically ischemic leg, as were distal motor, total motor, and sensory
      examination subscores (p < 0.01 for each). Sural sensory potentials were reduced
      or absent, frequently on both sides. The symptomatic limb had reduced tibial
      motor amplitudes and increased thermal (cold) sensory thresholds (p < 0.01 for
      both) whereas the distal latencies, conduction velocities, and vibration
      thresholds were similar in the two legs. CONCLUSIONS: There is a predominantly
      sensory neuropathy associated with chronic and critical limb ischemia.
      Neuropathic symptoms are often obscured by the effects of ischemia on other
      tissues. The neurophysiologic changes suggest that the underlying pathophysiology
      is a distal axonopathy affecting nerve fibers of all sizes. Measures of blood
      flow in the leg correlate with neurologic symptom scores, examination scores, and
      electrophysiologic testing.

PMID- 11571326
TI  - Prolonged orbicularis oculi activity: a major factor in apraxia of lid opening.
AB  - BACKGROUND: Apraxia of lid opening (ALO) is a nonparalytic inability to open the
      eyes at will in the absence of visible contraction of the orbicularis oculi (OOc)
      muscle. OBJECTIVE: To test the hypothesis that sustained activity of the OOc is a
      major factor in the difficulty in opening the eyes in this condition. METHODS:
      Lid movement detected in an electromagnetic field and electromyogram activity of
      the septal and pretarsal portions of the OOc were recorded in 12 healthy control
      subjects and 12 patients with a clinical diagnosis of ALO. The latencies to onset
      and to complete eye opening and the time during which eye opening was sustained
      were measured and analyzed in relation to OOc activity. RESULTS: The lid opening
      latencies and the lid movement duration were significantly increased in patients
      compared with control values. An abnormal persistence of OOc activity was present
      in 10 of the 11 patients with a delay in complete lid opening. The complete lid
      opening delay showed a strong positive correlation with the time it took to
      inhibit the OOc activity. This relationship fit the same linear regression in
      both groups. CONCLUSIONS: Patients with ALO show significant delays in eye
      opening. An abnormal persistence of OOc activity, detectable
      electromyographically but not clinically, could be the main factor contributing
      to the delay in lid opening in these patients.

PMID- 11571327
TI  - Language and spatial attention can lateralize to the same hemisphere in healthy
      humans.
AB  - BACKGROUND: Disorders of language classically occur after left brain lesions, and
      disorders of spatial attention after right brain lesions. It is unclear whether
      the hemispheric dissociation of functions is a fixed pattern of brain
      organization. OBJECTIVE: The authors determined whether lateralization of
      language and lateralization of spatial attention also dissociate in people with
      atypical (i.e., right hemispheric) language dominance. METHODS: The authors
      selected 10 subjects with typical, i.e., left hemispheric, and 10 with atypical,
      i.e., right hemispheric, language representation on a random basis from a sample
      of 326 healthy volunteers examined with functional transcranial Doppler
      sonography (fTCD) for language dominance. In these subjects, hemispheric
      lateralization of cerebral perfusion during a line bisection task was determined
      with fTCD. RESULTS: The authors found a dissociation between dominance for
      language and spatial attention in all but four subjects. In the latter subjects,
      there was a significant lateralization to the right hemisphere for both tasks.
      The four subjects showed normal intellectual, linguistic, and spatial
      performance, with normal EEG and MRI scans of the brain. CONCLUSION: Even in the
      absence of brain pathology, the same hemisphere can be dominant in control of
      both language and spatial attention.

PMID- 11571328
TI  - Striatal volume loss in HD as measured by MRI and the influence of CAG repeat.
AB  - BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative
      disease that results from the expansion of a trinucleotide (CAG) repeat on
      chromosome 4. Progressive degeneration of the striatum is the pathologic hallmark
      of the disease. Little is known about the regional selectivity of the
      neurodegeneration and its relationship to the genetic expansion. METHODS: The
      authors used high-resolution MRI to determine the relationship between the
      genetic expansion and the degree of striatal degeneration. Morphometric analyses
      of the striatum from high-resolution MR images from 27 subjects with HD were
      compared with those of 24 healthy control subjects. RESULTS AND CONCLUSIONS:
      Striatal volumes were reduced in subjects with HD as compared with control
      subjects, in agreement with previously published reports. Left-sided volumes were
      smaller than right-sided volumes in subjects with HD; in healthy subjects, right
      sided volumes were smaller. Finally, volume loss was significantly correlated
      with CAG repeat number. These results have potential implications for the design
      and assessment of therapeutic agents in the future.

PMID- 11571329
TI  - Fluid-attenuated inversion recovery: correlations of hippocampal cell densities
      with signal abnormalities.
AB  - BACKGROUND: Hippocampal sclerosis (HS) is characterized by hippocampal atrophy
      and increased signal on T2-weighted images and on fluid-attenuated inversion
      recovery (FLAIR) images. OBJECTIVE: To quantitate cell loss and compare it with
      signal abnormalities on FLAIR images. METHODS: Thirty-one patients with temporal
      lobe resection, pathologically proven HS, and Engel class I and II outcome were
      included: 20 with HS only and 11 with HS associated with pathologically proven
      cortical dysplasia (dual pathology). The signal intensity on FLAIR was rated as
      present or absent in the hippocampus and correlated with the neuronal losses in
      the hippocampus. RESULTS: FLAIR signal increases were present in 77% (24/31) of
      all patients studied. In patients with isolated HS, 90% (18/20) had ipsilateral
      signal increases, but in patients with dual pathology, only 55% (6/11; p < 0.02)
      showed FLAIR signal increase. Hippocampal cell losses were significantly higher
      in the isolated HS group. The average cell loss in patients with FLAIR signal
      abnormalities was 64.8 +/- 8.0% as compared with only 32.7 +/- 5.1% in patients
      with no FLAIR signal abnormalities. There was a significant positive correlation
      between the presence of signal abnormality and average hippocampal cell loss in
      both pathologic groups. CONCLUSIONS: Ipsilateral FLAIR signal abnormalities occur
      in the majority of patients with isolated HS but are less frequent in those with
      dual pathology. The presence of increased FLAIR signal is correlated with higher
      hippocampal cell loss.

PMID- 11571330
TI  - Transdermal nicotine in PD: a randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: An inverse association between cigarette smoking and the risk of
      idiopathic PD has been found in many epidemiologic studies. The therapeutic and
      possible neuroprotective effects of nicotine formulations on parkinsonian
      symptoms are controversial. METHODS: In a 12-week, randomized, double-blind,
      placebo-controlled trial, the efficacy and tolerability of transdermal nicotine
      patches as an add-on treatment for cardinal symptoms were evaluated in 32
      nonsmoking patients with PD. After a 1-week run-in phase, patients were
      randomized to receive nicotine patches (containing 17.5 mg nicotine in the first
      and 35.0 mg nicotine in the second and third weeks) or identically appearing
      placebo patches. After this treatment, 3 weeks without patch application
      followed. The same blinded examiner assessed the patients with the Columbia
      University Rating Scale, the Webster scale, the Schwab-England scale, a timed
      walking test, with an instrumental test for fine motor skills and hand tremor,
      and with the Hamilton Depression Scale. RESULTS: No significant drug effects
      between both groups were observed in any of the scores and quantitative tests.
      Side effects were mild and comparable in frequency between both groups.
      CONCLUSIONS: With the dosage and the period of treatment chosen, transdermal
      nicotine patches are not effective as an add-on treatment for symptoms of PD.

PMID- 11571331
TI  - Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive
      status epilepticus.
AB  - BACKGROUND: Although cIV-MDZ has emerged as a popular alternative to barbiturate
      therapy for refractory status epilepticus (RSE), experience with its use for this
      indication is limited. OBJECTIVE: - To evaluate the efficacy of continuous
      intravenous midazolam (cIV-MDZ) for attaining sustained seizure control in
      patients with RSE. METHODS: The authors reviewed 33 episodes of RSE treated with
      cIV-MDZ in their neurologic intensive care unit over 6 years. All patients were
      monitored with continuous EEG (cEEG). MDZ infusion rates were titrated to
      eliminate clinical and EEG seizure activity; cIV-MDZ was discontinued once
      patients were seizure-free for 24 hours. Acute treatment failures (seizures 1 to
      6 hours after starting cIV-MDZ), breakthrough seizures (after 6 hours of
      therapy), post-treatment seizures (within 48 hours of discontinuing therapy), and
      ultimate treatment failure (frequent seizures that led to treatment with
      pentobarbital or propofol) were identified. RESULTS: All patients were in
      nonconvulsive SE at the time cIV-MDZ was started; the mean duration of SE before
      treatment was 3.9 days (range 0 to 17 days). In addition to benzodiazepines, 94%
      of patients had received at least two antiepileptic drugs (AED) before starting
      cIV-MDZ. The mean loading dose was 0.19 mg/kg, the mean maximal infusion rate was
      0.22 mg/kg/h, and the mean duration of cIV-MDZ therapy was 4.2 days (range 1 to
      14 days). Acute treatment failure occurred in 18% (6/33) of episodes,
      breakthrough seizures in 56% (18/32), post-treatment seizures in 68% (19/28), and
      ultimate treatment failure in 18% (6/33). Breakthrough seizures were clinically
      subtle or purely electrographic in 89% (16/18) of cases and were associated with
      an increased risk of developing post-treatment seizures (p = 0.01). CONCLUSIONS:
      Although most patients with RSE initially responded to cIV-MDZ, over half
      developed subsequent breakthrough seizures, which were predictive of post
      treatment seizures and were often detectable only with cEEG. Titrating cIV-MDZ to
      burst suppression, more aggressive treatment with concurrent AED, or a longer
      period of initial treatment may reduce the high proportion of patients with RSE
      who relapse after cIV-MDZ is discontinued.

PMID- 11571332
TI  - Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family.
AB  - OBJECTIVE: To describe an unusual kindred with adult-onset ataxia and thalamic
      lesions detected by brain MRI. METHODS: The authors characterized clinical,
      laboratory, and pathologic features of the disease and sought linkage to
      previously recognized ataxia loci. RESULTS: Two sisters and a brother developed
      progressive ataxia, dysarthria, mild cognitive impairment, and sensorimotor
      neuropathy at age 30, combined with epilepsy in one sibling. MRI showed symmetric
      thalamic lesions, changes in brainstem gray matter, and white matter changes in
      the cerebellum. Autopsy in one of the patients revealed neuronal degeneration
      with a peculiar vacuolar change in thalamus, probably representing transsynaptic
      degeneration in response to deafferentation. Neuronal and secondary tract
      degeneration was observed in the spinal cord, cerebellum, and brainstem
      suggesting a spinocerebellar degeneration. The disorder appears to be transmitted
      as an autosomal recessive trait. Genetic and sequence analysis of the FRDA gene
      and comprehensive laboratory examinations excluded Friedreich's ataxia and other
      similar recessive diseases. CONCLUSION: Adult-onset recessive ataxia with
      bilateral thalamic lesions in this family may represent a distinct hereditary
      spinocerebellar ataxia.

PMID- 11571333
TI  - Unverricht-Lundborg disease in a five-generation Arab family: instability of
      dodecamer repeats.
AB  - BACKGROUND: Unverricht-Lundborg disease (ULD) is the prototypical form of
      progressive myoclonus epilepsy, and subjects are usually very photosensitive. ULD
      is caused by mutations in the cystatin B (CSTB) gene; the most common mutation is
      expansion of a dodecamer repeat near the promoter. The authors studied a five
      generation Arab family with ULD lacking photosensitivity. METHODS: An Arab family
      from the Galilee region of Israel with progressive myoclonus epilepsy was
      clinically evaluated. Blood samples were obtained from three living affected and
      16 unaffected individuals. Expansion of dodecamer repeat in the CSTB gene was
      examined. RESULTS: The three living affected individuals showed spontaneous and
      action myoclonus, ataxia, and mild dementia. EEG in two individuals showed
      generalized polyspike-wave without photosensitivity. The family structure with
      large sibships and multiple consanguineous loops allowed the authors to examine
      the gene over four generations of adults. The three living affected individuals
      were homozygous for repeat expansions and 11 of the 16 unaffected family members
      were heterozygous. Instability was demonstrated by the presence of expansions of
      different sizes occurring on the same haplotype background in this inbred family.
      Fragment size variations could be unequivocally detected in two sibships. The
      expansions were in the 49 to 54 dodecamer repeat range. Changes in one generation
      were small, 1 to 4 repeat units, consisting of either enlargements or
      contractions. CONCLUSIONS: Instability of the expanded dodecamer repeats in the
      cystatin B gene is frequent. Almost invariably, a small change is observed in
      parent-child transmission. The lack of photosensitivity in this family is
      unexplained.

PMID- 11571334
TI  - Clinical characteristics and topography of lesions in movement disorders due to
      thalamic lesions.
AB  - OBJECTIVE: To determine which thalamic subnuclei are involved in symptomatic
      unilateral movement disorders due to localized thalamic infarction, and the
      clinical characteristics of these abnormal movements. METHODS: The authors
      studied 22 patients with thalamic infarcts for their clinical presentation and
      the topography of the lesions, using three-dimensional T1-weighted MRI sequencing
      and stereotaxic analysis of the lesions. RESULTS: Patients were divided into four
      groups: 1) absence of abnormal involuntary movements (AIM) (nine patients); 2)
      isolated dystonic posture (two patients); 3) myoclonic dystonia (five patients);
      and 4) tremor or myoclonus (six patients). In patients with AIM, thalamic lesions
      were contralateral to the abnormal movements, involving the thalamogeniculate
      territory, centered on the ventral intermediate (Vim) and ventral caudal (Vc)
      nuclei. No significant difference in the volumes or center of mass of the lesions
      was found between patients with tremor and myoclonus and patients with dystonia,
      although the central nucleus and the internal part of the Vim nucleus were more
      consistently damaged in dystonic patients. CONCLUSION: Movement disorders related
      to thalamic lesions included: 1) myoclonic dystonia with predominating myoclonus
      and "thalamic" hand associating dystonic posture and slow, pseudo-athetoid
      movements, both related to lesions in the Vim and Vc nuclei of the thalamus; and
      2) postural and action tremor, also related to lesions in the Vim, similar to
      tremor associated with midbrain lesions, as a result of abnormal functioning of
      the cerebello-thalamic pathways.

PMID- 11571335
TI  - Cerebral microbleeds in CADASIL.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is a hereditary arteriopathy leading to
      recurrent cerebral infarcts and dementia. Intracerebral hemorrhage (ICH) has been
      described sporadically in patients with CADASIL, suggesting that the affected
      arteries in CADASIL are not bleed-prone. However, the presence of cerebral
      microbleeds, which often remain undetected on conventional MRI, has not been
      determined in CADASIL. OBJECTIVE: To determine whether cerebral vessels in
      patients with CADASIL are prone to microbleeding. METHODS: T2*-weighted gradient
      echo MRI, which is highly sensitive for visualizing microbleeds, was performed in
      patients with CADASIL and their family members (n = 63). Known risk factors for
      ICH were determined for all individuals. On an exploratory basis, the presence of
      cerebral microbleeds was correlated with demographic variables, vascular risk
      factors, disease progression, ischemic MR lesions, and genotype. RESULTS:
      Cerebral microbleeds were present in 31% of symptomatic CADASIL mutation
      carriers, predominantly in the thalamus. Vascular risk factors such as
      hypertension did not account for the microbleeds in these patients. Factors
      associated with microbleeds were age (p = 0.008), Rankin disability score (p =
      0.017), antiplatelet use (p = 0.025), number of lacunae on MRI (p = 0.009), and
      the Arg153Cys Notch3 mutation (p = 0.017). After correction for age, only the
      Arg153Cys mutation remained significantly associated with the presence of
      microbleeds. CONCLUSION: Patients with CADASIL have an age-related increased risk
      of intracerebral microbleeds. This implies that they may have an increased risk
      for ICH, which should be taken into account in CADASIL diagnosis and patient
      management.

PMID- 11571336
TI  - EEG criteria predictive of complicated evolution in idiopathic rolandic epilepsy.
AB  - BACKGROUND: Although so-called "benign" epilepsy with centrotemporal spikes
      (BECTS) always has an excellent prognosis with regard to seizure remission,
      behavioral problems and cognitive dysfunctions may sometimes develop in its
      course. To search for clinical or EEG markers allowing early detection of
      patients prone to such complications, the authors conducted a prospective study
      in a cohort of unselected patients with BECTS. METHODS: In 35 children with
      BECTS, academic, familial, neurologic, neuropsychological, and wake and sleep EEG
      evaluations were repeated every 6 to 12 months from the beginning of the seizure
      disorder up to complete recovery. RESULTS: In 25 of 35 patients (72%), behavioral
      and intellectual functioning remained unimpaired. In 10 of 35 patients (28%),
      educational performance and familial maladjustment occurred. These sociofamilial
      problems were correlated with impulsivity, learning difficulties, attention
      disorders, and minor (7/35 cases, 20%) or serious (3/35 cases, 8%) auditory
      verbal or visual-spatial deficits. Worsening phases started 2 to 36 months after
      onset and persisted for 9 to 39 months. Occurrence of atypical evolutions was
      significantly correlated with five qualitative and one quantitative interictal
      EEG pattern: intermittent slow-wave focus, multiple asynchronous spike-wave foci,
      long spike-wave clusters, generalized 3-c/s "absence-like" spike-wave discharges,
      conjunction of interictal paroxysms with negative or positive myoclonia, and
      abundance of interictal abnormalities during wakefulness and sleep. Clinical
      deterioration was not linked with seizure characteristics or treatment.
      CONCLUSION: Different combinations of at least three of six distinctive
      interictal EEG patterns and their long-lasting (> or =6-month) persistence seem
      to be the hallmarks of patients with BECTS at risk for neuropsychological
      impairments.

PMID- 11571337
TI  - Serum IFN neutralizing antibodies and neopterin levels in a cross-section of MS
      patients.
AB  - OBJECTIVE: To determine levels of serum interferon beta (IFNbeta) neutralizing
      antibody (NAb) and neopterin-an IFN biologic response marker-in patients with MS
      treated with Betaseron or Avonex. BACKGROUND: Controversy exists over the
      relative immunogenicity of IFNbeta-1a and IFNbeta-1b and the reasons for any such
      difference. To determine the role of patient profile and test methodology in
      IFNbeta, NAb levels need to be measured blindly and simultaneously in a
      predefined closely matched MS patient cohort. METHODS: Serum NAb and neopterin
      levels were measured in closely matched patients on Avonex (n = 98) or Betaseron
      (n = 64). NAb were determined by Athena Diagnostics and serum neopterin levels by
      Covance Laboratories using a competitive binding radioimmunoassay. RESULTS: More
      patients taking Betaseron (22%) than Avonex (7%) had elevated titers of NAb (p =
      0.008). Mean serum neopterin levels were lower in patients with high as compared
      to low NAb titers (p = 0.0002). No difference in mean neopterin levels was found
      comparing the total Betaseron group to the Avonex group; however, in the subset
      of patients with low NAb titers, mean neopterin levels were higher in the
      Betaseron than in the Avonex group (p = 0.027). A random cross-sectional sampling
      of patients on Avonex showed a decrease in neopterin levels over time between
      weekly doses. CONCLUSION: NAb are more commonly found with Betaseron than Avonex.
      More studies are needed to determine the correlation among serum neopterin
      levels, other biologic response markers, NAb, and disease activity in patients
      with MS being treated with IFNbeta.

PMID- 11571338
TI  - Localizing signs in positional vertigo due to lateral canal cupulolithiasis.
AB  - BACKGROUND: Different types of benign positional vertigo (BPV) have been
      recognized. The variant with permanent apogeotropic direction-changing lateral
      nystagmus in the supine position is particularly difficult to distinguish from
      central etiologies. OBJECTIVE: To identify clinical features of this variant of
      BPV, helping to establish its peripheral etiology. METHODS: In five patients
      without any evidence of neurologic disease and with this variant of positional
      vertigo, the behavior of nystagmus as a function of head position in space was
      studied. RESULTS: In the supine position, a null point for lateral nystagmus was
      identified, beyond which the nystagmus changed direction. This null point was
      evident when the head was turned 10 to 20 degrees to the side. In this position,
      the ipsilateral cupula of the lateral semicircular canal is aligned with the
      gravity vector. In two of the five patients, a null point was identified in
      pitch, beyond which the nystagmus reversed direction. This null point corresponds
      to the head position where the lateral canals are in an earth horizontal plane.
      CONCLUSION: From the behavior of lateral nystagmus in different head positions,
      the lateral canal system of the inner ear is shown to be gravity-sensitive and
      the side on which the cupula is affected can be determined.

PMID- 11571339
TI  - Cholesterol and Alzheimer's disease: is there a link?
AB  - The Abeta-amyloid peptide (Abeta), the main component of amyloid plaques, is
      derived by proteolytic cleavage from the amyloid precursor protein (APP).
      Epidemiologic and biochemical data suggest a link between cholesterol, APP
      processing, Abeta, and Alzheimer's disease. Two recent epidemiologic studies
      indicate that there is a decreased prevalence of AD associated with the use of
      cholesterol-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A
      reductase (HMG-CoA reductase inhibitors or statins). Experiments in cell culture
      and in vivo demonstrate that treatment with statins reduces production of Abeta.
      The authors discuss how cholesterol might modulate Abeta deposit formation. As
      neurons receive only small amounts of exogenous cholesterol, statins that
      efficiently cross the blood-brain barrier may reduce the amount of neuronal
      cholesterol below a critical level. Decreased neuronal cholesterol levels inhibit
      the Abeta-forming amyloidogenic pathway possibly by removing APP from cholesterol
      and sphingolipid-enriched membrane microdomains. In addition, depletion of
      cellular cholesterol levels reduces the ability of Abeta to act as a seed for
      further fibril formation. These intriguing relationships raise the hopes that
      cholesterol-lowering strategies may influence the progression of AD.

PMID- 11571340
TI  - Microvascular decompression for trigeminal neuralgia.

PMID- 11571341
TI  - An ALS-like syndrome with new HIV infection and complete response to
      antiretroviral therapy.
AB  - A 32-year-old woman presenting with a rapidly progressive ALS-like syndrome was
      found to be HIV positive with a CD4 count of 44/mm(3). The patient recovered
      completely during 1 year after treatment with nelfinavir, zidovudine, and
      lamivudine, and recovery is sustained nearly 4 years later. Recovery was
      accompanied by HIV RNA becoming undetectable in plasma and CSF.

PMID- 11571342
TI  - Apolipoprotein E genotype, coagulation, and survival following acute stroke.
AB  - The authors hypothesized that divergent influences of the APOE epsilon4 allele on
      ischemic and hemorrhagic stroke survival might result from differences in
      coagulation profiles. In 49 hemorrhagic stroke patients, epsilon4 carriers had
      higher partial thromboplastin time ratios (p < 0.01) than non-epsilon4 carriers.
      Among 529 ischemic stroke patients, increasing epsilon4 allele dose was
      associated with improved survival (p = 0.03) after adjusting for baseline NIH
      stroke scale (p = 0.00001) and partial thromboplastin time ratio (p = 0.01).
      Relative anticoagulation does not fully explain the survival advantage in
      epsilon4-carrying ischemic stroke patients.

PMID- 11571343
TI  - Intra-arterial urokinase for acute ischemic stroke: factors associated with
      complications.
AB  - The authors abstracted the records of 43 patients treated with intra-arterial
      urokinase for acute ischemic stroke to identify predictors of serious
      complications. Sixteen (37%) had such a complication. Higher urokinase dose (>1.5
      x 10(6) U), higher mean arterial blood pressure before treatment (>130 mm Hg),
      basilar occlusive strokes, and severe strokes were most predictive of these
      complications. Although urokinase is no longer manufactured, these findings
      identify patients at risk for complications from other intra-arterial
      thrombolytics.

PMID- 11571344
TI  - Drop attacks in older patients secondary to an otologic cause.
AB  - The clinical features and treatment of seven patients with drop attacks
      attributable to inner ear disease presenting after age 65 are described. A
      neurologic or cardiovascular cause of drop attacks was initially suspected.
      Audiovestibular testing documented a unilateral inner ear disorder. The salient
      clinical features of these cases are discussed. The patients underwent ablative
      vestibular surgery, and all compensated well and were free of vertigo and falls
      up to 10 years postoperatively.

PMID- 11571345
TI  - Oculomotor synkinesis following a midbrain stroke.
AB  - A 33-year-old man developed a complete third nerve palsy in the setting of acute
      bacterial endocarditis. MRI revealed an ischemic stroke in the cerebral peduncle
      involving the third nerve fascicle. Subsequently, he was observed to have
      paradoxic elevation of the eyelid on adduction and downgaze. To the authors'
      knowledge, this is the first demonstration of oculomotor synkinesis after an
      acquired, ischemic CNS lesion.

PMID- 11571346
TI  - Ring chromosome 20 epilepsy syndrome in children: electroclinical features.
AB  - Ring chromosome 20 mosaicism is associated with dysmorphic features, mental
      retardation, and intractable seizures, including recurrent episodes of
      nonconvulsive status epilepticus. The authors' findings in four children, all
      without dysmorphic features, indicate that mental deterioration and frequent
      subtle nocturnal frontal lobe seizures, associated with a characteristic EEG
      pattern, represent prominent additional clinical features not previously
      described in this syndrome. This emphasizes the importance of full-night video
      EEG in children with frontal lobe seizures and cognitive deterioration.

PMID- 11571347
TI  - A pilot tolerability and efficacy study of levetiracetam in patients with chronic
      myoclonus.
AB  - Levetiracetam was recently approved as adjunctive therapy for partial onset
      seizures. The authors conducted an open-label trial of levetiracetam in eight
      patients with chronic myoclonus. Patients were assessed by using the Unified
      Myoclonus Rating Scale. Levetiracetam was well tolerated. Three of five patients
      with cortical myoclonus experienced reductions in their myoclonus scores,
      providing support for a larger, placebo-controlled trial in cortical myoclonus.

PMID- 11571348
TI  - (1)H-MR spectroscopy is sensitive to subtle effects of perinatal asphyxia.
AB  - The authors performed neuropsychological and (1)H-MRS studies in 18 subclinical
      patients with antecedents of perinatal asphyxia (PA) and in 18 matched control
      subjects. Patients with PA showed reduced values of N-acetylaspartate (NAA) in
      both the basal ganglia and the midtemporal region (MTR) and reduced NAA/choline
      values in the MTR. Neuropsychological testing showed group differences in tasks
      related to attention and memory. These results indicate persistent dysfunctions
      in cerebral structures vulnerable to hypoxia and demonstrate the utility of MRS
      for the long-term evaluation of cerebral sequelae of neonatal asphyxia.

PMID- 11571349
TI  - Diagnostic accuracy and certainty from sequential evaluations in peripheral
      neuropathy.
AB  - Three masked neuromuscular experts analyzed the contribution of the data from
      sequential evaluations in predicting specific varieties of peripheral neuropathy
      in 72 patients. The largest improvement (16%) in diagnostic accuracy resulted
      from presentation of neurologic history. By contrast, diagnostic confidence
      increased gradually with presentation of additional medical information.
      Therefore, the authors conclude that for diagnostic accuracy and certainty,
      expert neuromuscular judgment and extensive characterizing or discriminative
      testing are needed.

PMID- 11571350
TI  - Atypical presentation of dopa-responsive dystonia: generalized hypotonia and
      proximal weakness.
AB  - Dopa-responsive dystonia (DRD) is an autosomal dominant disorder typically
      presenting as dystonia with diurnal variability. Described is an 8-year-old boy
      who had had waddling gait, generalized hypotonia, and proximal weakness since
      early childhood. He responded well to low-dose L-dopa. He had a point mutation of
      the GTP cyclohydrolase I gene. The patient's father and sister had the same
      mutation but did not have proximal weakness. GTP cyclohydrolase I deficiency can
      present with hypotonia and weakness.

PMID- 11571351
TI  - Genome-wide scan for Parkinson's disease: the GenePD Study.
AB  - A genome-wide scan for idiopathic PD in a sample of 113 PD-affected sibling pairs
      is reported. Suggestive evidence for linkage was found for chromosomes 1 (214 cM,
      lod = 1.20), 9 (136 cM, lod = 1.30), 10 (88 cM, lod = 1.07), and 16 (114 cM, lod
      = 0.93). The chromosome 9 region overlaps the genes for dopamine beta-hydroxylase
      and torsion dystonia. Although no strong evidence for linkage was found for any
      locus, these results may be of value in comparison with similar studies by
      others.

PMID- 11571352
TI  - Satellite potentials on EMG: neurophysiologic evidence of axonal transection in
      MS?
AB  - To detect signs of axonal damage in MS, the authors investigated the occurrence
      in EMG of motor unit action potentials with satellite potentials (SP-MUAP) in the
      upper limb muscles in 10 consecutive patients with MS with cervical spinal cord
      demyelinating lesions and 10 control subjects. Subjects' SP-MUAP rate was 0 to
      2.5% (median 0%) in the control group, and 0 to 17.5% (median 7.5%) in the MS
      group (p < 0.01). Motor unit remodeling secondary to axonal transection of spinal
      motor neurons traversing cervical demyelinating lesions may be hypothesized.

PMID- 11571353
TI  - TNFalpha production by CD4(+) T cells predicts long-term increase in lesion load
      on MRI in MS.
AB  - Reliable laboratory prognostic factors for MS are still lacking. The predictive
      value of markers of T-cell activation for long-term disease progression was
      investigated. Flow cytometry measurements were correlated to changes in Expanded
      Disability Status Scale and MR T2 lesion load over 36 months in 14 patients with
      secondary progressive MS. A correlation was found between the percentage of tumor
      necrosis factor-alpha-producing CD4(+) T cells at baseline and the change in T2
      lesion load during 3-year follow-up (r = 0.79, adjusted r(2) = 0.59, p = 0.001).

PMID- 11571354
TI  - Downregulation of transforming growth factor-beta1 in interferon-beta1a-treated
      MS patients.
AB  - The authors report an intense downregulation of transforming growth factor-beta1
      (TGF-beta1) serum levels 4 weeks from start of interferon-beta1a (IFN-beta1a)
      treatment at 44 microg/week in 271 patients with relapsing-remitting MS, which
      was still present after 1 year (p < 0.001). In line with previous data,
      interleukin-10 serum levels did not vary significantly. These results indicate
      that the immunomodulatory effects of IFN-beta might not be restricted to the
      postulated anti-inflammatory mechanisms and address the role of TGF-beta in the
      pathogenesis of MS.

PMID- 11571355
TI  - Quantification of tissue damage in AD using diffusion tensor and magnetization
      transfer MRI.
AB  - The authors measured mean diffusivity (D) and magnetization transfer ratio (MTR)
      of the brain from 18 patients with AD and 16 healthy control subjects. The peak
      heights of cortical gray matter (cGM) D (p < 0.001) and MTR (p < 0.001)
      histograms were lower and average cGM D (p < 0.01) higher in patients with AD
      than in control subjects. A composite MR score based on brain volume and cGM MTR
      peak height was correlated with patient cognitive impairment (r = 0.65, p =
      0.003). This preliminary study presents a novel approach to quantify AD-related
      tissue damage in-vivo.

PMID- 11571356
TI  - Safety of anticoagulation for cerebral venous thrombosis associated with
      intracerebral hematoma.

PMID- 11571357
TI  - Dexfenfluramine effective in drug-resistant temporal lobe epilepsy.

PMID- 11571358
TI  - Different histopathology accounting for a decrease in myocardial MIBG uptake in
      PD and MSA.

PMID- 11571359
TI  - Intoxication with riluzole in Huntington's disease.

PMID- 11571360
TI  - Infarction of the "hand knob" area.

PMID- 11571361
TI  - Historical aspects of botulinum toxin.

PMID- 11571362
TI  - Suppression of post-hypoxic and post-encephalitic myoclonus with levetiracetam.

PMID- 11571363
TI  - Areas of consensus in withdrawing life-sustaining treatment in the neurointensive
      care unit.

PMID- 11571364
TI  - Myocardial injury after hemorrhage into the lateral medulla oblongata.

PMID- 11571368
TI  - Some high pitched thoughts on chest examination.

PMID- 11571370
TI  - Hyperaldosteronism: recent concepts, diagnosis, and management.

PMID- 11571371
TI  - Management of shoulder pain in patients with stroke.
AB  - Shoulder pain affects from 16% to 72% of patients after a cerebrovascular
      accident. Hemiplegic shoulder pain causes considerable distress and reduced
      activity and can markedly hinder rehabilitation. The aetiology of hemiplegic
      shoulder pain is probably multifactorial. The ideal management of hemiplegic
      stroke pain is prevention. For prophylaxis to be effective, it must begin
      immediately after the stroke. Awareness of potential injuries to the shoulder
      joint reduces the frequency of shoulder pain after stroke. The multidisciplinary
      team, patients, and carers should be provided with instructions on how to avoid
      injuries to the affected limb. Foam supports or shoulder strapping may be used to
      prevent shoulder pain. Overarm slings should be avoided. Treatment of shoulder
      pain after stroke should start with simple analgesics. If shoulder pain persists,
      treatment should include high intensity transcutaneous electrical nerve
      stimulation or functional electrical stimulation. Intra-articular steroid
      injections may be used in resistant cases.

PMID- 11571372
TI  - Formal education programmes for senior house officers: comparison of experience
      in three hospital specialties.
AB  - This study was designed to compare the attendance rate of senior house officers
      (SHOs) in three specialties at formal educational events, examine experiences of
      protected time, use of educational objectives, and perceived barriers to
      attendance and evaluate differences found in the context of variations in
      training practice within each specialty. A quantitative questionnaire survey was
      completed by Trent region SHOs in obstetrics and gynaecology, general medicine,
      and accident and emergency posts. An independent researcher visited a selection
      of educational programme events over a two month span, recorded attendances, and
      administered the questionnaire. Attendance rates ranged from 40.8% of those in
      obstetrics and gynaecology jobs to 55.4% of those in accident and emergency jobs.
      The questionnaire findings found that service commitments were a major obstacle
      to attendance for the majority of those in obstetrics and gynaecology and general
      medicine jobs, while relatively few of the accident and emergency SHOs specified
      any barriers. SHOs in accident and emergency jobs had significantly more
      protected time for education and found educational objectives to be more widely
      used by senior staff. The findings suggest that the planned integration of formal
      education programmes with appropriate working pattern systems--in this case full
      shifts within accident and emergency departments--will result in SHOs receiving a
      better deal in terms of provision and structure of education.

PMID- 11571373
TI  - Prescription of eye drops.
AB  - The aim of this study was to assess whether patients have their ocular drops
      correctly prescribed during non-ophthalmic admissions to hospital. A
      retrospective review of notes of patients who were admitted to hospital for
      general medical or surgical care, while on regular eye drops at the time of
      admission was performed. Twenty two patients were on regular ocular medication
      when admitted. Only seven out of 22 patients had their eye drops correctly
      prescribed. Furthermore, six patients had been prescribed topical beta-blockers,
      yet suffered from medical conditions that may have been aggravated by these
      drops. These findings demonstrate that the majority of patients on drops do not
      have their medication correctly prescribed during non-ophthalmic admissions to
      hospital. Also topical beta-blockers continue to be inappropriately prescribed.

PMID- 11571374
TI  - Review of the complications and medicolegal implications of vasectomy.

PMID- 11571375
TI  - Pseudoarthrosis in neurofibromatosis type-1.

PMID- 11571376
TI  - Obstetric difficulties due to Graves' disease.

PMID- 11571369
TI  - Imaging of the pulmonary manifestations of systemic disease.

PMID- 11571377
TI  - A rare presentation of a common disease.

PMID- 11571378
TI  - Adrenal mass in a diabetic with hypergastrinaemia.

PMID- 11571379
TI  - Adult intussusception--an elusive diagnosis.

PMID- 11571380
TI  - Acute respiratory failure in a middle aged woman.

PMID- 11571381
TI  - Cor pulmonale: variation on a theme.

PMID- 11571382
TI  - Rectal bleeding in a patient with portal hypertension.

PMID- 11571383
TI  - A state of confusion.

PMID- 11571384
TI  - Dysphagia in a patient with palmoplantar keratoderma.

PMID- 11571385
TI  - Decreased sexual function in a young man.

PMID- 11571397
TI  - Unexplained hypokalaemia and metabolic alkalosis.

PMID- 11571398
TI  - Fever with pain in bilateral shoulder joints.

PMID- 11571399
TI  - A 25 year old woman presenting with bleeding disorder and nystagmus.

PMID- 11571400
TI  - Painful chest wall swelling.

PMID- 11571402
TI  - The case against the gun industry.

PMID- 11571403
TI  - Precautions against biological and chemical terrorism directed at food and water
      supplies.
AB  - Deliberate food and water contamination remains the easiest way to distribute
      biological or chemical agents for the purpose of terrorism, despite the national
      focus on dissemination of these agents as small-particle aerosols or volatile
      liquids. Moreover, biological terrorism as a result of sabotage of our food
      supply has already occurred in the United States. A review of naturally occurring
      food- and waterborne outbreaks exposes this vulnerability and reaffirms that,
      depending on the site of contamination, a significant number of people could be
      infected or injured over a wide geographic area. Major knowledge gaps exist with
      regard to the feasibility of current disinfection and inspection methods to
      protect our food and water against contamination by a number of biological and
      chemical agents. However, a global increase in food and water safety initiatives
      combined with enhanced disease surveillance and response activities are our best
      hope to prevent and respond quickly to food- and waterborne bioterrorism.

PMID- 11571404
TI  - Comparative accuracy of clinical estimate versus menstrual gestational age in
      computerized birth certificates.
AB  - OBJECTIVE: This study compares gestational age data obtained by clinical estimate
      with data calculated from the date of the last menstrual period (LMP) as recorded
      on birth certificates. METHODS: The authors analyzed 476,034 computerized birth
      records from three overlap years, that is, those that contained both menstrual
      and clinical estimates of gestational age, concentrating on cases within the
      biologically plausible range of 20-44 weeks. RESULTS: The overall exact
      concordance between the two measurements was 46%. For +1 week it was 78%, and for
      +2 weeks it was 87%. Incidence of prematurity was 16% with menstrual gestational
      age, while it was 12% with clinical estimate. About 47% of the LMP-based preterm
      births were classified as term by clinical estimate. Eighty-three percent of
      clinical estimate-based preterms were also preterms by LMP-based gestation.
      Birthweight frequency distribution curves for LMP-based gestational age are
      bimodal, indicating probable miscoding of term births. An apparent over
      representation of births coded as exactly 40 weeks by clinical estimate suggests
      rounding off near term for this method. CONCLUSION: Agreement between menstrual
      and clinical estimates of gestational age occurs most often close to term, with
      significant disagreement in preterm and postterm births. Use of different methods
      of determining gestation in different years or geographic populations will result
      in artifactual differences in important indicators such as prematurity rate.

PMID- 11571405
TI  - The role of state public health agencies in genetics and disease prevention:
      results of a national survey.
AB  - OBJECTIVES: The onset and severity of the clinical expression of most diseases
      that are of public health importance are influenced by genetic predisposition.
      The ability to assess human genetic predisposition for many diseases is
      increasing rapidly. Therefore, state public health agencies should be
      incorporating new developments in genetics and disease prevention into their core
      functions of assessment, policy development, and assurance. The authors assessed
      the status of this process. METHODS: The Council of State and Territorial
      Epidemiologists (CSTE) surveyed states about projects and concerns related to
      genetics and public health activities. Respondents were the Health Officer, the
      Maternal and Child Health/Genetics Program Director, the Chronic Disease Program
      Director, and the Laboratory Director. Where applicable, responses were
      categorized into assessment, policy development, and assurance functions.
      RESULTS: Thirty-eight (76%) state health departments responded. Ongoing genetics
      activities were assurance (82%), assessment (17%), and policy development (2%).
      In contrast, Health Officers responded that future genetics activities would be
      distributed differently: assurance, 41%; assessment, 36%; and policy development,
      23%. Future assurance activities would be largely educational. Topics of interest
      and recently initiated activities in genetics were primarily assessment
      functions. Funding was the greatest concern, followed by lack of proven disease
      prevention measures and outcomes data. CONCLUSIONS: State health departments
      recognize a need to realign their activities to meet future developments in
      genetics. Lack of adequate resources, proven disease prevention measures, and
      outcomes data are potential barriers. Public health agencies need to develop a
      strategic plan to meet the opportunities associated with the development and
      implementation of genetic tests and procedures.

PMID- 11571406
TI  - Evaluating the health significance of hazardous air pollutants using monitoring
      data.
AB  - OBJECTIVE: Though many contaminants are released into the atmosphere, in the US
      only six air pollutants-ozone, particulate matter, sulfur dioxide, carbon
      monoxide, nitrogen dioxide, and lead-are closely monitored and carefully assessed
      for health significance. Other pollutants, even if highly toxic, are neither
      widely monitored nor routinely assessed at the national level. The goal of this
      study was to analyze the availability of information needed to characterize the
      health significance of hazardous air pollutants, focusing on urban areas in
      California. METHODS: The authors compared different approaches to identifying
      which contaminants should be considered hazardous air pollutants of potential
      health concern; reviewed the availability of toxicity values for these
      pollutants; and analyzed the usefulness of air monitoring data from California
      agencies for determining populations risks, by comparing method detection limits
      with health benchmarks. RESULTS: Approaches to identifying air contaminants of
      possible health concern differ. Toxicity values are not available for many
      hazardous air pollutants, including those identified in the Clean Air Act. In
      California, monitoring data are available for many, though not all, pollutants of
      concern. Monitoring methods for several pollutants do not have adequate
      sensitivity to detect all relevant concentrations. CONCLUSION: The information
      necessary to fully assess the health significance of hazardous air pollutants is
      not currently available.

PMID- 11571407
TI  - Patients with diagnosed diabetes mellitus can be accurately identified in an
      Indian Health Service patient registration database.
AB  - OBJECTIVE: The computerized patient registration databases maintained by the
      Indian Health Service (IHS) represent a potentially important source of data
      about the epidemic of diabetes among American Indian and Alaskan Native people.
      The purpose of this study is to determine the accuracy of this data source, and
      to identify the optimal search criteria to identify patients with a diagnosis of
      diabetes in an IHS patient registration database. METHODS: The authors compared
      the results of a series of computerized searches to a "gold standard" sample of
      465 manually reviewed charts from a large IHS facility. RESULTS: Among patients
      ages 15 years and older, the best criterion for identifying patients diagnosed
      with diabetes was the presence of at least one purpose of visit narrative
      identified by a 250.00 to 250.93 ICD-9 code. The presence of a single
      computerized code for diabetes identified patients with diagnosed diabetes with a
      sensitivity of 92% (95% confidence interval [CI] 81, 97), a specificity of 99%
      (95% CI 98, 99), and a calculated positive predictive value of 94% (95% CI 85,
      99). In a separate chart review of 462 charts of patients who had at least one
      250.00 to 250.93 ICD-9 code recorded in the database, 435 had a diagnosis of
      diabetes for an observed positive predictive value of 94%. Because the prevalence
      of diabetes varies by age of the patient, the positive predictive value of the
      ability to identify patients with diabetes also varies by age. CONCLUSION: A
      computerized search of an IHS patient database can identify patients with a
      diagnosis of diabetes with an accuracy that is similar to the reported accuracy
      from other health care system databases.

PMID- 11571408
TI  - Differences in asthma prevalence between samples of American Indian and Alaska
      Native children.
AB  - OBJECTIVES: To better understand the prevalence of asthma among American Indian
      and Alaska Native (AI/AN) children and to explore the contribution of locale to
      asthma symptoms and diagnostic assignment, the authors surveyed AI/AN middle
      school students, comparing responses from metropolitan Tacoma, Washington (metro
      WA) and a non-metropolitan area of Alaska (non-metro AK). METHODS: Students in
      grades 6-9 completed an asthma screening survey. The authors compared self
      reported rates of asthma symptoms, asthma diagnoses, and health care utilization
      for 147 children ages 11-16 self-reporting as AI/AN in metro WA and 365 in non
      metro AK. RESULTS: The prevalences of self-reported asthma symptoms were similar
      for the metro WA and non-metro AK populations, but a significantly higher
      percentage of metro WA than of non-metro AK respondents reported having received
      a physician diagnosis of asthma (OR 2.33; 95% CI 1.23, 4.39). The percentages of
      respondents who reported having visited a medical provider for asthma-like
      symptoms in the previous year did not differ. CONCLUSIONS: The difference in
      rates of asthma diagnosis despite similar rates of asthma symptoms and
      respiratory-related medical visits may reflect differences in respiratory disease
      patterns, diagnostic labeling practices, or environmental factors. Future
      attempts to describe asthma prevalence should consider the potential contribution
      of non-biologic factors such as diagnostic practices.

PMID- 11571409
TI  - Hazardous air pollutants: inside and out.

PMID- 11571410
TI  - Air quality measures and public health policy.

PMID- 11571412
TI  - DHHS blueprint for action on breastfeeding.

PMID- 11571413
TI  - Enhancing public health research and learning through community-academic
      partnerships: the Michigan experience.

PMID- 11571416
TI  - New drugs for old.

PMID- 11571417
TI  - Dexmedetomidine.
AB  - Effective use of sedative-hypnotic and analgesic agents is an integral part of
      providing patient comfort and safety. Of the numerous drugs administered,
      benzodiazepines, propofol, and narcotics are the most popular. Even these proven,
      time-tested sedative-hypnotics and analgesics are not perfect, however, and
      modern intensive care demands a more ideal product. The development of
      dexmedetomidine, an alpha2-agonist, is an attempt to improve sedative/analgesic
      use and provide a drug that possesses the characteristics outlined in Table 1. It
      stimulates alpha2-adrenergic receptors in the locus ceruleus to provide sedation
      and in the spinal cord to enhance analgesia. It also causes sympatholysis via
      central and peripheral mechanisms. Dexmedetomidine binds alpha2-receptors eight
      times more avidly than clonidine and is shorter acting. It was initially
      evaluated as an anesthetic, but was associated with excessive bradycardia and
      hypertension, followed by hypotension. In late 1999, dexmedetomidine was approved
      for adult ICU use for less than 24 hours as a sedative infusion. It currently
      lacks approval in Europe. Most of the clinical experience with dexmedetomidine
      has been with surgical patients undergoing cardiac and vascular procedures.
      Careful patient selection and proper drug infusion are needed to avoid excessive
      deleterious hemodynamic results. Slower bolus loading over 20 minutes results in
      minimally decreased heart rate and blood pressure. Continuous infusion maintains
      unique sedation (patients appear to be asleep, but are readily roused), analgesic
      sparing effect, and minimal depression of respiratory drive. More experience with
      dexmedetomidine infusion in medical ICU patients and patients with complex end
      organ dysfunction such as respiratory failure or systemic inflammatory response
      syndrome is needed before conclusions can be drawn about the drug's potential for
      wider application and its long-term (> 24 h) safety and effectiveness.

PMID- 11571418
TI  - Remifentanil.
AB  - Remifentanil is an opioid with a unique pharmacokinetic profile. Its metabolism
      by nonspecific esterases results in rapid and uniform clearance leading to highly
      predictable onset and offset of action. This review will describe the features
      that set remifentanil apart from other opioids and outline its potential
      usefulness in a critical care setting. Most studies on remifentanil have been in
      postoperative neurosurgical and cardiothoracic ICU settings. In the former, the
      agent has proved especially useful because rapid predictable emergence from
      sedation allows regular clinical evaluation. Remifentanil also prevents procedure
      associated rise in intracranial pressure. In the cardiac setting, the drug
      provides excellent intraoperative hemodynamic control while allowing return of
      spontaneous ventilation within minutes of discontinuation of the infusion. One
      study suggests that the use of remifentanil will reduce the need for
      postoperative intensive care, especially after hepatic transplantation.

PMID- 11571419
TI  - New anti-Gram-positive agents.
AB  - As the prevalence of resistant Gram-positive organisms in the critical care unit
      has increased, so have the associated morbidity and mortality and the cost of
      their treatment. As a result, more toxic and less active second-line agents and
      combinations of agents are used, often with limited evidence of clinical benefit.
      Although widely used, the role of glycopeptides is limited by increasing
      resistance and poor pharmacokinetics. New agents now in use, such as
      quinupristin/dalfopristin and Linezolid (Zyvox; Pharmacia & Upjohn, Kalamazoo,
      MI), show promise, as do diverse agents in development. The future is likely to
      bring greater therapeutic choice but, inevitably, further resistance.

PMID- 11571420
TI  - Optimal use of existing and new antifungal drugs.
AB  - Clinicians are increasingly aware that fungal pathogens are a significant cause
      of morbidity and mortality in hospitalized patients. Historically, these
      infections occurred in severely immunocompromised patients who were undergoing
      treatment for hematological malignancy or solid organ transplantation. Currently,
      however, systemic fungal infections are commonly seen in debilitated patients who
      are being nursed in intensive care or high-dependency units. These infections are
      mostly caused by Candida albicans but there is a growing proportion of strains of
      non- albicans Candida spp, some with reduced susceptibility to commonly used
      antifungals. The limited armamentarium of antifungal agents to date has meant
      that amphotericin B continues to be considered the most effective therapeutic
      agent albeit with a poor record of treatment-limiting side effects. The past
      decade has seen some encouraging developments in antifungal therapy. Three lipid
      formulations of amphotericin B showing reduced toxicity compared with the
      desoxycholate formulation are now licensed. There are three investigational
      triazoles currently undergoing evaluation that should prove important additions
      to existing members of this class. The echinocandin caspofungin is the first of a
      new class of antifungal agents with a novel mode of action, which has recently
      been approved for use in the United States.

PMID- 11571421
TI  - Current immunosuppressant regimens: considerations for critical care.
AB  - While current immunosuppressive drug regimens have significantly increased the
      rate of successful transplantation outcomes, they convey potentially serious and
      overlapping adverse effects. Cyclosporine and tacrolimus are the cornerstones of
      current immunosuppression, achieving excellent one-year renal graft survival
      rates. Other promising new drugs include sirolimus, which has been demonstrated
      to reduce efficacy failure rates among renal transplant recipients, and
      everolimus, which is currently undergoing clinical trials. Agents targeting novel
      sites in the immune response or disrupting the ischemia-reperfusion cascades are
      currently under development. Among them, only FTY720 is undergoing large-scale
      human clinical trials. With its unique mechanism of action and synergistic
      interactions with cyclosporine and sirolimus, it may provide the foundation for a
      new era in immunosuppression.

PMID- 11571422
TI  - Nutrition in patients with acute pancreatitis.
AB  - Acute pancreatitis is a disease with varying severity. Patients with the mild
      form do not require nutritional support because oral intake is resumed rapidly.
      Studies on nutritional support in acute pancreatitis have included patients with
      both mild and severe disease. In this heterogeneous group, total parenteral
      nutrition did not improve outcome compared with no nutrition at all. This is
      caused in part by an increase in septic complications during total parenteral
      nutrition. Likewise, no benefit from enteral nutrition was observed compared with
      no nutrition, probably because the group was heterogeneous or because nutritional
      goals were not achieved. Patients with severe acute pancreatitis become
      profoundly catabolic. This group undoubtedly requires nutritional support to
      treat undernutrition. The limited available data indicate that enteral nutrition,
      if well tolerated, is superior to parenteral nutrition for patients with severe
      acute pancreatitis. Based on current knowledge, a combination of early total
      parenteral nutrition and enteral nutrition is advisable as soon as enteral
      nutrition is tolerated. Monitoring of gut function is crucial in this situation.

PMID- 11571423
TI  - Hypothermia for the management of intracranial hypertension in acute liver
      failure.
AB  - Increased intracranial pressure in patients with acute liver failure remains a
      major cause of mortality. Treatment options are limited, and without urgent liver
      transplantation, mortality rates of up to 90% are common in those who fulfill
      criteria for poor prognosis. Several studies in animal models of acute liver
      failure set the stage for the clinical application of moderate hypothermia in
      humans. Few patients are treated with hypothermia for increased intracranial
      pressure. However, data indicate that moderate hypothermia is a safe and
      effective method of treatment for increased intracranial pressure that is
      unresponsive to other medical therapies, and that this treatment can be used as a
      successful bridge to liver transplantation. Recent data also suggest that
      increases in intracranial pressure can be prevented during the dissection and
      reperfusion phases of liver transplantation for acute liver failure if patients
      are kept hypothermic during the surgical procedure. This article focuses on the
      use of moderate hypothermia for the treatment of increased intracranial pressure
      in patients with acute liver failure.

PMID- 11571424
TI  - Serious intra-abdominal infections.
AB  - Serious intra-abdominal infections continue to plague patients and vex surgeons
      and other caregivers. The mortality rate can exceed 20%, and the morbidity
      associated with severe cases (eg, enterocutaneous fistula, ventral hernia
      resulting from open-abdomen management) requires reoperation and months of
      convalescence. There is no consensus as to the definition of severity and a
      paucity of studies that focus on treatment at the severe end of the spectrum.
      Attempts are being made to address the adequacy of operative management (adequacy
      of "source control") in the context of randomized antibiotic trials. The surgical
      procedure is the primary treatment modality for most types of intra-abdominal
      infection, whereas antibiotic therapy is usually adjunctive. It remains to be
      determined whether the adequacy of source control can be quantified meaningfully.

PMID- 11571425
TI  - Abdominal compartment syndrome in the intensive care unit.
AB  - The abdominal compartment syndrome is an increasingly recognized complication of
      both medical and surgical patients in the ICU setting. This syndrome has been
      described in a wide variety of clinical scenarios and results from a persistent
      elevation in intra-abdominal pressure characterized by graded organ system
      dysfunction. Manifestations of abdominal compartment syndrome include
      cardiovascular, pulmonary, renal, splanchnic, and neurologic impairment. The
      diagnosis of abdominal compartment syndrome requires a high level of clinical
      suspicion combined with an increased intra-abdominal pressure, usually obtained
      via urinary bladder pressure measurement. Patients at risk for abdominal
      compartment syndrome warrant close monitoring and we recommend prompt abdominal
      decompression following documentation of increased intra-abdominal pressure in
      the setting of physiologic compromise. Abdominal compartment syndrome can
      significantly contribute to the morbidity and mortality of both medical and
      surgical patients alike in the ICU. The signs and symptoms of abdominal
      compartment syndrome should become familiar to all critical care practitioners.

PMID- 11571426
TI  - Perioperative management of liver transplantation patients.
AB  - Perioperative care involves many disciplines, each of which contributes in
      important ways. Changes in liver-transplantation care during the last 40 years
      can be attributed to the accumulation of improvements, discoveries, and
      technologic improvements across different disciplines. Here we review some of the
      articles that were published during the last year that relate to these advances.

PMID- 11571427
TI  - Reducing variation and standardizing practice in the intensive care unit.

PMID- 11571428
TI  - Variation in intensive care unit outcomes: a search for the evidence on
      organizational factors.
AB  - This study was undertaken to determine the extent of empirical evidence on the
      role of organizational factors in the critical care literature and to categorize
      these factors. Studies evaluating organizational factors were identified through
      electronic and hand searching of the critical care literature. Sixty-three
      publications relating to 54 different studies were identified. The studies were
      grouped into eight main categories: staffing, teamwork, volume and pressure of
      work, protocols, admission to intensive care, technology, structure, and error.
      Studies evaluating organizational factors exist in the critical care literature,
      and there is evidence that the number is increasing each year. Results indicate
      that organizational factors may have an impact on mortality after case mix
      adjustment. Some areas have been investigated more thoroughly than others and are
      ripe for systematic review. Variation in case mix adjusted hospital mortality
      after intensive care is an old theme. This study has shown that emerging data
      will help us understand mortality differences and deliver better outcomes for
      patients.

PMID- 11571429
TI  - Developing and implementing measures of quality of care in the intensive care
      unit.
AB  - As consumers, payers, and regulatory agencies require evidence regarding quality
      of care, the demand for intensive care unit (ICU) quality measures will likely
      grow. ICU providers and professional societies may need to partner with experts
      in quality measurement to develop and implement quality measures. This essay
      outlines the steps for developing and implementing quality measures and provides
      examples of potential ICU quality indicators. Outcome measures, in particular
      mortality rates, require risk adjustment, making data collection burdensome and
      broad implementation unlikely. On the other hand, structure and process measures
      may be feasible to implement broadly. Given the steps for developing quality
      measures outlined in this essay and the growing evidence in the literature
      regarding the impact of ICU care, the future should realize the development and
      implementation of ICU quality indicators that are rigorously developed and
      provide insights into opportunities to improve the quality of ICU care.

PMID- 11571430
TI  - New ways to reduce unnecessary variation and improve outcomes in the intensive
      care unit.
AB  - The care of critically ill patients and the advent of the modern day intensive
      care unit (ICU) present a large person power and cost burden to society. The high
      cost of critical care is attributed to high overhead expenses (eg, experienced
      staff and equipment), high resource utilization (eg, pharmaceutical resources,
      lab testing, imaging procedures), and high demand for services. Pathways to
      standardize numerous facets of patient care have been shown to improve the
      efficiency of delivery of care and to reduce resource utilization, and are
      becoming the most sought-after means of improving patient outcomes and reducing
      overall ICU expenditures. A number of large, randomized, prospective trials have
      demonstrated that protocol-based strategies can not only reduce variation and
      cost of ICU medicine but also improve morbidity and mortality of critically ill
      patients requiring ICU support. In this article, we discuss examples of these
      trials investigating four major areas of modern ICU medicine: ventilator
      management, ventilator weaning, sedation and analgesia, and blood transfusions.

PMID- 11571431
TI  - A general approach to broader sharing in organ allocation.

PMID- 11571432
TI  - FTY720: altered lymphocyte traffic results in allograft protection.

PMID- 11571433
TI  - IL-15--friend or foe in transplantation rejection?

PMID- 11571434
TI  - Predictive value of in vitro assessment of direct alloresponses in transplant
      recipients?

PMID- 11571435
TI  - Sirolimus: another cause of drug-induced interstitial pneumonitis.

PMID- 11571436
TI  - Sirolimus: searching for its niche or a therapy that has come of age?

PMID- 11571437
TI  - Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting
      in improved renal function and lower blood pressure.
AB  - INTRODUCTION: This study evaluated whether cyclosporine (CsA) could be eliminated
      from a sirolimus (Rapamune, rapamycin, SRL)-CsA-steroid (ST) regimen at 3 months.
      METHODS: This was an open-label study conducted in Europe, Australia, and Canada.
      Upon enrollment, 525 primary (90%) or secondary (10%) renal allograft recipients
      with cadaveric (89%) or living (11%) donors received 2 mg of sirolimus (troughs>5
      ng/ml), CsA, and steroids. At 3 months+/-2 weeks, eligible patients were
      randomized (1:1) to remain on SRL-CsA-ST or to have CsA withdrawn and therapy
      continued with SRL (troughs 20-30 ng/ml)-ST. RESULTS: At 12 months, overall graft
      and patient survival were 89.1% and 94.9%, respectively. In the 430 (82%)
      randomized patients, there was no difference in graft survival (95.8% vs. 97.2%,
      SRL-CsA-ST vs. SRL-ST) or patient survival (97.2% vs. 98.1%, respectively). The
      incidence of biopsy-confirmed primary acute rejection was 13.1% during the
      prerandomization period. After randomization, the acute rejection rates were 4.2%
      and 9.8% for SRL-CsA-ST and SRL-ST, respectively (P=0.035). Renal function
      (calculated glomerular filtration rate, 57 vs. 63 ml/min, P<0.001) and blood
      pressure significantly improved when CsA was withdrawn. Hypertension, CsA
      nephrotoxicity, hyperuricemia, and Herpes zoster occurred statistically more
      frequently in patients remaining on CsA, whereas thrombocytopenia, abnormal liver
      function tests, and hypokalemia were reported more often for SRL-ST therapy.
      CONCLUSION: Sirolimus, CsA, and steroids for 3 months posttransplant, followed by
      elimination of CsA, is a safe and effective alternative to continuous therapy
      with sirolimus, CsA, and steroids that can result in better renal function and
      lower blood pressure.

PMID- 11571438
TI  - Characteristics of sirolimus-associated interstitial pneumonitis in renal
      transplant patients.
AB  - BACKGROUND: Sirolimus, a promising new immunosuppressive drug for organ
      transplantation, is currently associated with side effects, such as
      thrombocytopenia and hyperlipidemia. METHODS: Eight renal transplant recipients,
      who developed unexplained interstitial pneumonitis during sirolimus therapy, were
      extensively re-screened for all causes of pneumonitis. RESULTS: Interstitial
      pneumonitis was constantly characterized by bilateral interstitial infiltrates on
      chest x-rays and lung computed tomography scans, with marked general symptoms in
      all patients but one. Bronchoalveolar lavage (BAL) disclosed lymphocytic
      alveolitis (mainly of the CD4 type) in seven patients and alveolar hemorrhage in
      one. Transbronchial lung biopsies, performed in two patients, showed
      bronchiolitis obliterans with organizing pneumonia combined with lymphocytic
      interstitial pneumonitis. Pulmonary infections were ruled out by specific
      stainings and cultures of BAL, bronchial aspirates, and blood cultures. After the
      elimination of all possible causes, sirolimus-induced pneumonitis was considered
      probable. Discontinuation of sirolimus in seven cases and dose reduction in the
      remaining case dramatically improved clinical and radiological status within a
      few weeks and led to complete resolution within 3 months. CONCLUSIONS: Sirolimus
      is very probably responsible for interstitial pneumonitis on the following
      grounds: (a) occurrence of pneumonitis during sirolimus therapy; (b) absence of
      any other causes; and (c) resolution within 3 months of sirolimus discontinuation
      or dose reduction. Sirolimus should now be added to the list of possible causes
      of pulmonary complications after renal transplantation. Discontinuation or dose
      reduction of sirolimus led to complete and lasting resolution of symptoms.

PMID- 11571439
TI  - Mixed allogeneic chimerism as a reliable model for composite tissue allograft
      tolerance induction across major and minor histocompatibility barriers.
AB  - BACKGROUND: Although prolonged composite tissue allograft (CTA) survival is
      achievable in animals using immunosuppressive drugs, long-term immunosuppression
      of CTAs in the clinical setting may be unacceptable for most patients. The
      purpose of this study was to develop a model for reliable CTA tolerance induction
      in the adult rat across a major MHC mismatch without the need for long-term
      immunosuppression. METHODS: Mixed allogeneic chimeras were prepared by using rat
      strains with strong MHC incompatibility [WF (RT1Au), ACI (RT1Aa)] WF + ACI-->WF,
      n=23. The bone marrow (BM) of recipient animals was pretreated with low-dose
      irradiation (500-700 cGy), followed by reconstitution with a mixture of T cell
      depleted syngeneic (WF) and allogeneic (ACI) cells. Additionally, the recipient
      animals received a single dose of anti-lymphocyte serum (10 mg) 5 days before
      bone marrow transplantation (BMT) and tacrolimus (1 mg/kg/day) from the day
      before BMT to 10 days post-BMT. Hindlimb transplants were performed 12 months
      after BMT. Five animals received a limb allograft irradiated (1000 cGy) just
      before transplantation. Rat chimeras were characterized (percentage of donor
      cells present within the bloodstream) by flow cytometry at 3 and 12 months after
      BM reconstitution and after hindlimb transplantation. RESULTS: Peripheral blood
      lymphocyte chimerism (WF/ACI) remained stable >12 months after BM reconstitution
      in 18/23 animals. Multi-lineage chimerism of both lymphoid and myeloid lineages
      was present, suggesting that engraftment of the pluripotent rat stem cell had
      occurred. In animals with donor chimerism >60% (n=18) no sign of limb rejection
      was present for the duration of the study. All animals with chimerism <20% (n=5)
      developed moderate signs of rejection clinically and histologically. Gross motor
      and sensory reinnervation (weight bearing, toe spread) developed at >60 days in
      14/21 rats. Postoperative flow cytometry studies demonstrated stable chimerism in
      all animals studied (n=10). Five out of five animals with irradiated limb
      transplants showed no sign of GVHD at >100 days. CONCLUSIONS: Stable mixed
      allogeneic chimerism can be achieved in a rat hindlimb model of composite tissue
      allotransplantation. Hindlimb allografts to mixed allogeneic chimeras exhibit
      prolonged, rejection-free survival. Partial functional return should be expected.
      The BM transplanted as part of the hindlimb allograft plays a role in the
      etiology of GVHD. Manipulating that BM before transplantation may influence the
      incidence of GVHD. This represents the first reliable rat hindlimb model
      demonstrating rejection-free CTA survival in an adult animal across a major MHC
      mismatch without the long-term need for immunosuppressive agents.

PMID- 11571440
TI  - Apoptosis versus necrosis during cold storage and rewarming of human renal
      proximal tubular cells.
AB  - BACKGROUND: A recent clinical study demonstrated that in renal allografts
      preserved in the cold apoptosis occurred soon after reperfusion. The mode of cell
      death during cold storage is generally considered necrotic. Whether apoptosis
      occurs as a part of cold storage is uncertain. The objective was to determine in
      human renal tubular cells whether apoptosis is specific for rewarming or it also
      occurs during cold storage and whether it could be modified. METHODS AND RESULTS:
      Cold storage (4 degrees C) of primary human renal proximal tubular epithelial
      (RPTE) in University of Wisconsin (UW) solution up to 48 hr caused a time
      dependent increase in cell death measured by lactic dehydrogenase (LDH) release
      and vital dye exclusion methods. Transmission electron microscopy (TEM)
      demonstrated that cell death in the cold was necrotic, involving considerable
      mitochondrial disruption, and was not apoptotic. The TUNEL assay that provides a
      specific, quantitative measure for apoptosis showed no increase in TUNEL
      positivity during flow cytometry of cells stored in cold: 37 degrees C, 0.23+/
      0.14%; 24 hr cold, 0.23+/-0.1%; 48 hr cold, 1.79+/-0.58%. Annexin-V staining, a
      sensitive method for detecting early apoptosis, similarly showed no increase in
      positively stained cells during cold storage. Addition of antioxidants 2-methyl
      aminochroman and deferoxamine to UW solution inhibited necrotic cell death and
      preserved mitochondrial structure. In contrast to cold storage alone, rewarming
      (37 degrees C for 24 hr) of cold stored cells, however, resulted in significant
      apoptosis (TUNEL positive: 48 hr cold: 2+/-0.6%, 48 hr cold and 24 hr rewarming:
      54+/-17%), which was confirmed by the TEM based on typical apoptotic features.
      Addition of 2-MAC and DFO significantly inhibited rewarming-induced apoptotic
      cell death (plus 2-MAC: 3+/-1%, plus DFO: 3+/-2%). CONCLUSION: Our study in human
      tubular cells provides evidence that cold storage per se does not result in
      apoptosis, but is primarily necrotic. However, rewarming is associated with
      significant apoptosis in the presence of ongoing necrosis, speculatively due to
      the activation of the apoptotic enzymic process of sublethally injured cells.
      Inclusion of antioxidants in the storage solution confers protection against both
      cold storage and rewarming-induced necrosis and apoptosis.

PMID- 11571441
TI  - Intrahepatic expression and release of vascular endothelial growth factor
      following orthotopic liver transplantation in the rat.
AB  - BACKGROUND: Morphological and functional changes to sinusoidal endothelial cells
      mediated by soluble factors released from activated Kupffer cells, including
      cytokines, are considered pivotal events in ischemia/reperfusion injury (IRI) to
      liver grafts. Vascular endothelial growth factor (VEGF) is an endothelial cell
      specific cytokine with potent pro-inflammatory and mitogenic effects. We
      investigated the possible role of VEGF in IRI to liver grafts using a syngeneic
      rat orthotopic liver transplantation model. METHODS: Transplantation was
      performed in Lewis rats using livers preserved for various periods of time (24-48
      hr) in University of Wisconsin solution at 4 degrees C. Systemic VEGF levels were
      measured by enzyme-linked immunosorbent assay (ELISA). Intrahepatic VEGF
      expression was analyzed by Northern blotting and in situ hybridization. The
      effects of anti-VEGF neutralizing antibody treatment on the extent of IRI were
      assessed by measuring liver function tests, lipid peroxidation, and
      metalloproteinase activity. RESULTS/CONCLUSION: VEGF is expressed and released in
      a biphasic pattern during the early postoperative period after liver
      transplantation. Anti-VEGF antibody treatment, administered during reperfusion,
      decreased the degree of damage, suggesting that VEGF may have a role in IRI to
      liver grafts.

PMID- 11571442
TI  - Transplantation of hepatocytes in nonhuman primates: a preclinical model for the
      treatment of hepatic metabolic diseases.
AB  - BACKGROUND: The transplantation of isolated hepatocytes in large animals,
      including nonhuman primates, must be evaluated before clinical trials are
      performed. However, in the absence of large transgenic animals and large-animal
      (as opposed to small-animal) models of genetic deficiencies, it is difficult to
      evaluate the fate of transplanted hepatocytes, their localization, survival, and
      function within the parenchyma of the host liver. In this work, we aimed to
      develop a technique for delivering hepatocytes to the liver of a nonhuman primate
      and to evaluate their localization and functionality in the short term. METHODS:
      A 20% hepatectomy was performed in 34 cynomolgus monkeys (Macaca fascicularis)
      and hepatocytes were isolated. Hepatocytes were labeled in vitro with a
      recombinant retrovirus expressing the beta-galactosidase gene and returned to the
      liver by infusion through a portal catheter left in place. Liver biopsies were
      performed 4 and 7 d after transplantation. RESULTS: Twenty-four monkeys underwent
      surgery to define the necessary technical adjustments and to optimize conditions.
      Six monkeys died. The whole protocol, including the transplantation of
      genetically marked hepatocytes and procurement of liver biopsies, was performed
      in the remaining 10 monkeys. In eight monkeys, transplanted hepatocytes
      expressing the beta-galactosidase gene were widely distributed in the portal
      tracts, sinusoids, and hepatocyte plates of the host liver 4 and 7 d after
      transplantation. CONCLUSIONS: We have developed an experimental nonhuman primate
      model for the evaluation of hepatocyte transplantation. We demonstrated the
      engraftment and functioning of transplanted hepatocytes in the host liver 4 and 7
      d after transplantation.

PMID- 11571443
TI  - Neuropathy in miniature swine after administration of the mutant diphtheria toxin
      based immunotoxin, pCD3-CRM9.
AB  - BACKGROUND: Effective in vivo T-cell depletion is a critical component of many
      transplantation tolerance protocols. We have previously demonstrated T-cell
      depletion in miniature swine using a CRM9-based CD3-immunotoxin, pCD3-CRM9. CRM9
      is a mutant form of diphtheria toxin (DT) that binds less efficiently than wild
      type DT to the DT receptor (proHB-EGF) of primates. In this report, we describe
      and characterize the dose-dependent neurotoxicity associated with CRM9-based
      immunotoxin administration in swine. METHODS: Miniature swine were treated with
      varying doses of pCD3-CRM9 followed by daily monitoring for symptoms of
      neuropathy, including limb weakness, paresis, sluggishness, and/or respiratory
      distress. Animals demonstrating severe respiratory distress were euthanized and
      peripheral nerve, spinal cord, and skeletal muscle tissue samples were obtained
      at autopsy for microscopic examination. Unconjugated CRM9 was administered to one
      animal to define its toxicity independent of the effects of T-cell depletion.
      RESULTS: Excellent T-cell depletion was obtained using doses of pCD3-CRM9 greater
      than 0.1 mg/kg. However, neurotoxicity was observed at these doses, as manifested
      by transient muscle weakness or paresis, which in some cases progressed to
      respiratory failure and death. Dorsal root ganglia samples revealed pathological
      changes typical of diphtheritic polyneuropathy. The animal receiving unconjugated
      CRM9 exhibited the same neurotoxic side effects as those receiving the pCD3-CRM9
      conjugate. CONCLUSIONS: Administration of pCD3-CRM9 immunotoxin provides
      excellent T-cell depletion in miniature swine but is associated with significant
      dose-dependent neurotoxicity. A possible reason for CRM9-associated neurotoxicity
      in swine, but not primates, is suggested on the basis of a known amino acid
      difference in the exodomain of the DT receptor (proHB-EGF) of swine compared with
      that of primates.

PMID- 11571444
TI  - Hemodynamic response to continuous infusion of dobutamine in Alagille's syndrome.
AB  - BACKGROUND: Alagille's syndrome is a rare condition that is characterized by
      paucity of interlobular bile ducts and peripheral pulmonary artery stenosis.
      Liver transplantation in the setting of peripheral pulmonary stenosis and right
      ventricular hypertension seems to be associated with a higher mortality, which
      raises the concern that these patients are unable to increase their cardiac
      output in the immediate posttransplantation period to meet the demands of
      reperfusion and early graft dysfunction and cope with further increases in
      pulmonary vascular resistance. METHOD: Cardiac catheterization was performed in
      15 children with Alagille's syndrome and peripheral pulmonary artery stenosis to
      measure the cardiac output response to dobutamine infusion. The cardiac output
      was measured before and during each increment of infusion of dobutamine at 10
      microg/kg/min and 20 microg/kg/min by using a thermodilution catheter placed in
      the pulmonary artery. RESULTS: There was a significant change in the baseline
      cardiac index (P<0.001) with an infusion of 20 microg/kg/min of dobutamine with
      an increase from 4.4(1.0) L/min/m2 to 6.4(1.5) L/min/m2. There was, however, a
      wide variation between individuals in the increase in cardiac index, ranging from
      7.3-95%. There was no correlation between the baseline systolic right
      ventricular/aortic pressure ratios and the increase in cardiac index (r=0.1086).
      CONCLUSION: The increase in cardiac index, in response to dobutamine in patients
      with Alagille's syndrome, is independent of the more conventional measurement of
      the right ventricular pressure. This method of producing a hemodynamic response
      is closer to the response that results after liver transplantation, and thus, it
      may be a better way of predicting the outcome of liver transplantation in these
      patients.

PMID- 11571445
TI  - Orthotopic liver transplantation for autoimmune hepatitis and cryptogenic chronic
      hepatitis in children.
AB  - BACKGROUND: Autoimmune hepatitis (AIH) and cryptogenic chronic hepatitis (CCH)
      are important causes of liver failure in children, frequently necessitating
      orthotopic liver transplantation (OLT). The aim of this study is to review
      disease progression and potential differences between subgroups of children with
      AIH and CCH. METHODS: The medical records of 65 children diagnosed with AIH or
      CCH between 1980 and 1998 were evaluated. RESULTS: The median age at presentation
      was 9 years, 8 months (range 4 months-19 years), and the median follow-up period
      was 8 years (range 3 months-18 years, 10 months). Forty-one patients (63%) were
      female. Twenty-eight patients were Hispanic, 28 were Caucasian, 8 were African
      American, and 1 was Asian. Forty-three patients (66%) were diagnosed with type 1
      AIH, 8 (12%) with type 2 AIH, and 14 (22%) with CCH. Forty patients (62%)
      underwent OLT (51% of those with type 1 AIH, 75% of those with type 2 AIH, and
      86% of those with CCH). Thirteen (33%) of the transplanted patients experienced
      disease recurrence. African-American patients experienced a significantly higher
      rate of disease recurrence post-OLT than did Hispanic patients. Seven patients
      (11%) died, two without OLT, and five posttransplantation. CONCLUSIONS: AIH and
      CCH frequently necessitate OLT in children. CCH is a more aggressive disease than
      Type 1 AIH among children with these disorders. Ethnicity influences the rate of
      disease recurrence after liver transplantation.

PMID- 11571446
TI  - Changes in hepatitis C virus population in serum and peripheral blood mononuclear
      cells in chronically infected patients receiving liver graft from infected
      donors.
AB  - BACKGROUND: We have previously studied hepatitis C (HCV)-infected recipients of
      livers from HCV-infected donors and found that either the donor's strain or the
      recipient's strain predominate in serum. The current study was undertaken to
      determine whether these changes are complete and whether they are reflected in
      the population of virus associated with peripheral blood mononuclear cells
      (PBMCs). METHODS: We analyzed HCV ribonucleic acid from sequential serum and PBMC
      samples from 11 and 8 patients, respectively. The relatively stable NS5 region
      was chosen for analysis because it allowed for dependable identification of donor
      and recipient strains. Viral sequences were analyzed by direct sequencing and by
      sensitive strain-specific polymerase chain reaction assays. These assays were
      capable of detecting the minor sequence present at a concentration 1:104-10-7
      below that of the major sequence. RESULTS: Five patients retained their original
      infecting strain; the donor strain was detected only transiently. In the
      remaining six patients, recipient strain was detected for the first few weeks,
      after which only the donor strain was consistently present. However, in one
      patient the second nondominant strain was detected from the background of the
      major strain on a single occasion 8 months after transplantation. All changes in
      serum were closely paralleled by those occurring in PBMCs. CONCLUSIONS: Viral
      population changes in the setting of liver transplantation from HCV-infected
      donors to HCV-infected recipients occur simultaneously in PBMCs and serum. The
      takeover of one strain by another in PBMC- and serum-derived viral populations
      seemed to be complete and long lasting.

PMID- 11571447
TI  - Results of 3-year phase III clinical trials with daclizumab prophylaxis for
      prevention of acute rejection after renal transplantation.
AB  - BACKGROUND: Daclizumab (Zenapax, Roche Pharmaceuticals), a humanized monoclonal
      antibody directed against the alpha chain of the interleukin 2 receptor, has been
      shown to reduce the incidence of acute rejection at 6 months after renal
      transplantation in two phase III clinical trials. This report presents the
      combined 1- and 3-year outcomes of kidney transplant recipients who participated
      in these two phase III clinical trials. METHODS: Data from two multicenter,
      randomized, placebo-controlled trials were evaluated with regard to graft
      survival, patient survival, incidence of malignancies (including lymphoma), renal
      function (serum creatinine and glomerular filtration rate [GFR]), and current
      maintenance immunosuppressive regimen. In addition, the impact of acute rejection
      and acute rejection requiring treatment with antilymphocyte therapy upon 3-year
      graft survival was evaluated. Daclizumab was compared to placebo on a background
      of cyclosporine (CsA), azathioprine, and corticosteroids (triple therapy, TT) or
      CsA and corticosteroids (double therapy, DT). RESULTS: Treatment with daclizumab
      in the pooled analysis demonstrated a significant reduction in the incidence of
      biopsy-proven acute rejection episodes at 12 months posttransplant (43% vs. 28%,
      P<0.001). The 3-year graft survival was not significantly different between
      placebo and daclizumab-treated patients in the TT trial (83% vs. 84%) or in the
      DT trial (78% vs. 82%). Pooled patient survival was excellent in both placebo-
      (91%) and daclizumab- (93%) treated patients. The incidence of malignancies or
      posttransplant lymphoproliferative disorder (PTLD) in placebo- versus daclizumab
      treated groups was comparable in both clinical trials. Renal function was similar
      between placebo- and daclizumab-treated groups in both the TT and DT trials. The
      occurrence of delayed graft function, acute rejection requiring antilymphocyte
      therapy at 6 months, and acute rejection at 12 months posttransplant were
      associated with decreased graft survival rates at 3 years posttransplant.
      CONCLUSIONS: The beneficial effect of daclizumab prophylaxis upon the incidence
      of acute rejection after renal transplant with TT or with DT was not associated
      with adverse clinical sequelae, including the development of PTLD, at 3 years
      posttransplant. There was no beneficial effect of daclizumab on graft survival at
      3 years, but the trial was inadequately powered to detect this. Both studies
      showed excellent graft and patient survival at 3 years.

PMID- 11571448
TI  - A pilot study of steroid-free immunosuppression in the prevention of acute
      rejection in renal allograft recipients.
AB  - BACKGROUND: Corticosteroids have been a mainstay of rejection prophylaxis for
      several decades, despite the multiple adverse effects of long-term use, including
      weight gain, hyperlipidemia, diabetes, hypertension, and bone disease. The
      detrimental effect of steroids on the metabolic profile begins in the early
      posttransplantation period, and the complete avoidance of steroids in
      transplantation would therefore be optimal. We hypothesized that the addition of
      mycophenolate mofetil (MMF) and a humanized monoclonal anti-CD25 antibody
      (daclizumab) to a cyclosporine (CsA microemulsion)-based immunosuppression
      protocol would permit transplantation without steroids. METHODS: Steroid-free
      renal transplantation was attempted in 57 patients treated with daclizumab, MMF,
      and CsA. Twenty-eight patients received kidneys from living donors; the remaining
      29 received cadaveric grafts. RESULTS: At 1 year, patient and graft survival were
      95% and 89%, respectively. Fourteen patients (25%) experienced rejections, of
      which 13 were readily reversed with steroids; 1 patient required OKT3. Mean serum
      creatinine at 12 months for patients not experiencing rejection was 149+/-58
      micromol/L, compared with 158+/-102 micromol/L for those experiencing rejection.
      Five patients required hospitalization for infection; no patients developed
      lymphoproliferative disease. At baseline, 17 patients required 3 or more
      antihypertensive medications, compared with 2 patients at 1 year. Three of 43
      nondiabetic patients developed diabetes during the study. There was no
      significant reduction in lumbar or femoral bone density. CONCLUSIONS: On the
      basis of these positive results, we believe steroid avoidance with this
      immunosuppressive regimen merits further study.

PMID- 11571450
TI  - Proton nuclear magnetic resonance analysis of hepatic bile from donors and
      recipients in human liver transplantation.
AB  - The current shortage of donor organs in liver transplantation has led experienced
      transplant centers to use more "marginal" grafts. The development of a reliable
      technique of bile collection gives access to hepatic bile from donors and
      recipients for bile analysis to characterize the grafts. Proton nuclear magnetic
      resonance analysis has been applied to the study of bile for more than 30 years,
      showing encouraging results. This is the first study where proton nuclear
      magnetic resonance analysis has been applied to hepatic bile from selected liver
      grafts to evaluate its potential role in graft assessment. Hepatic bile was
      collected from eight liver donors (four with normal and four with steatotic
      grafts) during organ retrieval and four transplant recipients (two with good
      early graft function and two with primary dysfunction) immediately after graft
      reperfusion. A Varian Unity+ NMR spectrometer, operating at 11.7 Tesla (500 MHz
      for 1H), was used to obtain the proton nuclear magnetic resonance spectra. The
      results showed that the hepatic bile from steatotic grafts collected before
      transplantation had more intense phosphatidylcholine head group resonance than
      bile from normal grafts. It also showed slower clearance of University of
      Wisconsin solution in grafts with subsequent primary graft dysfunction,
      suggesting a slower recovery of bile secretion. These preliminary findings
      suggest that proton nuclear magnetic resonance analysis might help to
      differentiate the characteristics of bile acids and biliary lipids from normal
      and steatotic grafts. The monitoring of the resonance signal of University of
      Wisconsin solution washout, bile acid, and biliary lipid secretion may help to
      predict the development of primary graft dysfunction and avoid the need for
      retransplantation.

PMID- 11571449
TI  - Sirolimus for rescue and primary immunosuppression in transplanted children
      receiving tacrolimus.
AB  - AIMS: The role of sirolimus (SRL) as a rescue agent (n=42) and as a component of
      primary immunosuppression (n=8) was evaluated in a mixed population of 50
      transplanted children receiving tacrolimus (liver: 26, heart: 5, intestinal: 5,
      liver-intestine: 9, lung: 1, bone marrow: 1, liver-kidney: 1, multivisceral: 1).
      Rescue indications for tacrolimus (TAC) failure were recurrent acute rejection
      and acute rejection complicating withdrawal of immunosuppression in
      posttransplant lymphoproliferative disorder (PTLD). Rescue indications for TAC
      toxicity were nephrotoxicity, pancreatitis, seizures, hypertrophic
      cardiomyopathy, and graft-versus-host disease. RESULTS: Mean age at rescue was
      11.5 years and mean follow-up was 204 (range 18-800) days. As primary
      immunosuppression, SRL+TAC prevented early acute rejection in 7/8 children. The
      indication for rescue resolved in 33/42 children. In children with TAC toxicity,
      this was associated with decrease in TAC doses by 50%, significant improvements
      in renal function, and continuing decline in Epstein-Barr virus (EBV) viral load
      in PTLD patients. Serious adverse events led to discontinuation of SRL in 9/42
      rescue patients, 3 of them also experienced acute rejection. Three additional
      children also experienced acute rejection on SRL therapy (overall incidence 6/50,
      12%). Pharmacokinetic analysis in the first week of SRL administration suggested
      a short half-life (11.8+/-5.5 hr, n=21). CONCLUSIONS: SRL and reduced-dose TAC
      may achieve adequate immunosuppression without compromising renal function or
      enhancing EBV viremia significantly.

PMID- 11571451
TI  - Living-donor versus cadaveric liver transplantation for non-resectable small
      hepatocellular carcinoma and compensated cirrhosis: a decision analysis.
AB  - BACKGROUND: Cadaveric liver transplantation is effective for nonresectable early
      hepatocellular carcinoma. However, the scarcity of cadaveric organs has prompted
      some centers to use living donors, which guarantees transplantation, but entails
      a risk to the donor. In the absence of controlled trials, decision analysis can
      be used to help explicate the tradeoffs involved when considering living donor
      versus cadaveric liver transplantation for nonresectable early hepatocellular
      carcinoma. METHODS: Using a Markov model, a hypothetical cohort of patients with
      Child's A cirrhosis and a single 3.5-cm tumor received one of three strategies:
      1) no transplant; 2) intent to perform cadaveric liver transplantation; or 3)
      living donor liver transplantation. Data were obtained from natural history and
      retrospective studies. All probabilities in the model were varied simultaneously
      using a Monte Carlo simulation. RESULTS: Living-donor liver transplantation was
      the best strategy, improving life expectancy by 4.5 years compared with cadaveric
      liver transplantation. This strategy remained dominant even when varying severity
      of cirrhosis, age, tumor doubling time, tumor growth pattern, blood type,
      regional transplant volume, initial tumor size, and rate of progression of
      cirrhosis. CONCLUSIONS: Living-donor liver transplantation should confer a
      substantial survival advantage for patients with compensated cirrhosis and non
      resectable early stage hepatocellular carcinoma.

PMID- 11571452
TI  - Donor horseshoe kidneys for transplantation.
AB  - BACKGROUND: Experience with donor horseshoe kidneys for transplantation is very
      limited. Currently, horseshoe kidneys may be underutilized for transplantation
      because of the greater incidence of vascular anomalies, associated renal
      anomalies, and predisposition to renal disease. METHODS: In this report, we
      review five transplantations using horseshoe kidneys: the largest reported
      institutional experience. In addition, a review of all published cases in the
      English literature is performed. RESULTS: All five patients underwent successful
      renal transplantations with a median follow-up of 35 months. One patient lost his
      kidney from recurrent disease soon after transplantation. CONCLUSION: With
      appropriate reconstruction of the vessels, careful division of the isthmus, and
      avoidance of ureteral obstruction, long-term data revealed good graft survival of
      donor horseshoe kidneys in renal transplantation.

PMID- 11571453
TI  - Pretransplant donor-specific helper T cell reactivity as a tool for tailoring the
      individual need for immunosuppression.
AB  - BACKGROUND: A reliable immunological assay for quantification of donor-specific
      alloreactivity to identify patients at risk for future allograft rejection would
      be a helpful tool in organ transplantation. Therefore, we questioned whether the
      T cell reactivity in patients measured before transplantation was predictive for
      the occurrence of acute rejection during the first year after kidney
      transplantation. METHODS: The pretransplant T cell reactivity of peripheral blood
      mononuclear cells to donor and third-party antigens was tested in mixed
      lymphocyte cultures, and to tetanus toxoid. In addition, we measured the
      frequency of donor and third-party reactive helper T lymphocyte precursor and
      cytotoxic T lymphocyte precursors using limiting dilution analysis. RESULTS:
      Patients who experienced acute rejection had significantly higher donor-specific
      mixed lymphocyte cultures responses (n=38; median stimulation index): 113 vs. 15,
      P=0.005) and helper T lymphocyte precursor frequency (n=37; median 194/106 vs.
      62/106, P=0.009) measured before transplantation compared to patients without
      acute rejection. All patients with a low mixed lymphocyte culture response
      (stimulation index</=20; 13/13 vs. 12/25, P=0.001) and an undetectable helper T
      lymphocyte precursor frequency (<10/106 peripheral blood mononuclear cells; 7/7
      vs. 17/30, P=0.04) before transplantation did not experience acute rejection. The
      donor-specific cytotoxic T lymphocyte precursor frequency (n=34; median 53/106
      vs. 28/106, P=0.58) and tetanus toxoid-reactivity (n=38; median stimulation
      index: 53 vs.16, P=0.56) measured before transplantation did not correlate with
      acute rejection. No correlation between third-party reactivity and acute
      rejection was observed. CONCLUSIONS: From these results we conclude that despite
      the current HLA matching criteria, undetectable helper T lymphocyte precursor
      frequency and low mixed lymphocyte culture responses against donor antigens
      measured before transplantation are predictive for a rejection-free first
      posttransplant year. These in vitro assays can be used to identify patients who
      require less immunosuppression after transplantation.

PMID- 11571454
TI  - Prospective randomized trial to assess the value of preemptive oral therapy for
      CMV infection following liver transplantation.
AB  - BACKGROUND: With the development of sensitive tests to detect cytomegalovirus
      (CMV) viremia, preemptive approaches become a reasonable alternative to general
      CMV prophylaxis. We performed a randomized trial comparing pp65-antigenemia
      guided preemptive therapy using oral ganciclovir with symptom-triggered
      intravenous ganciclovir treatment. METHODS: Eighty-eight of 372 liver transplant
      recipients developed antigenemia early after orthotopic liver transplantation.
      Twenty-eight symptomatic patients with antigenemia were excluded from
      randomization and treated with intravenous ganciclovir. Sixty pp65-antigen
      positive asymptomatic patients were randomized to receive either oral ganciclovir
      3x1 g/day for 14 days (group 1) or no preemptive treatment (group 2). Patients
      that developed CMV disease were treated with intravenous ganciclovir 2x5 mg/kg
      body weight for 14 days. The high-risk (Donor+/Recipient-) patients were equally
      distributed in the two study groups. RESULTS: Three of 30 (10%) patients on oral
      ganciclovir developed mild to moderate CMV disease compared with 6/30 (20%)
      patients in the control group. In the Donor+/Recipient- patients, the incidence
      of CMV disease was 1/6 and 3/7. All disease episodes resolved after intravenous
      treatment. The 1- and 3-year patient and organ survival was the same in the study
      groups and in the patients with or without CMV infection. No deaths related to
      CMV occurred. CONCLUSIONS: The positive predictive value of pp65-antigenemia for
      the development of CMV disease was very low, and, in 28/88 patients (32%),
      antigenemia did not precede symptoms. Therefore, pp65-antigenemia is of limited
      value in deciding on the timing and need for ganciclovir therapy after liver
      transplantation.

PMID- 11571455
TI  - Interleukin-15 is the main mediator of lymphocyte proliferation in cultures mixed
      with human kidney tubular epithelial cells.
AB  - BACKGROUND: Interleukin- (IL) 15 is a potent non-T cell-derived cytokine with IL
      2-like activities. Elevated levels of IL-15 expression were observed in biopsies
      of acutely rejected human kidney grafts. We tested the role of IL-15 in mixed
      lymphocyte kidney reaction (MLKR) and the effects of immunosuppressive drugs on
      this reaction. METHODS: Primary cultures of human tubular epithelial cells (TEC)
      were stimulated by interferon-gamma and treated with cyclosporin A (CsA, 10-1000
      ng/ml), rapamycin (Rapa, 2.5-10 ng/ml), and dexamethasone (Dex, 10-10-10-7 M). IL
      15 levels were measured by ELISA. To induce MLKR, we seeded OKT3-prestimulated
      allogenic human peripheral blood mononuclear cells (PBMC) on a monolayer of TEC
      in the presence of CsA (25-250 ng/ml), Rapa (0.25-1 ng/ml), and Dex (10-10-10-7
      M). PBMC proliferation was quantified by 3H-thymidine incorporation. RESULTS:
      CsA, Dex, and Rapa had no effect on IL-15 production by TEC. The presence of TEC
      induced marked proliferation of PBMC. Pretreatment of TEC with IFN-gamma enhanced
      MLKR in direct correlation with the increased IL-15 levels. MLKR was blocked by
      anti-IL-15, but not significantly by anti-IL-2 monoclonal antibody. Contrary to
      Rapa and Dex, CsA failed to inhibit MLKR CONCLUSIONS: IL-15 is a major mediator
      of lymphocyte proliferation in MLKR. Its production by TEC was unaffected by CsA,
      Rapa, and Dex. However, IL-15 activity is effectively inhibited by Rapa and Dex
      but not by CsA. The diversity in the effects of the various drugs is probably
      related to the different mechanisms. Our results support the possible involvement
      of renal IL-15 in graft rejection and suggest that resistance to CsA treatment is
      related to its failure to decrease IL-15 activity.

PMID- 11571456
TI  - Dendritic cells support hematopoiesis of bone marrow cells.
AB  - BACKGROUND: We previously observed that vaccination of normal mice with bone
      marrow (BM) -derived dendritic cells (DCs) could increase the number of
      peripheral white blood cells (WBCs) and platelets. In the present study, we
      investigated the potential of DCs to support the hematopoiesis of BM cells in
      vitro and in vivo. METHODS: In the absence of exogenous cytokines, the expansion
      of CD34+ stem cells was observed when cultured with DC-derived supernatant or
      contact cocultured with DC. After culture in supernatant of DCs or contact
      coculture with DCs for 3 days, CD34+ progenitor cells were cultured in the
      semisolid media to test their ability to generate the clonogeneic cells. Then, BM
      cells combined with DCs or not were transferred into lethally irradiated
      syngeneic recipients to determine the effects of DCs on hematopoietic recovery.
      RESULTS: After culture in the supernatant of DCs, especially in the supernatant
      of OVA-DCs (OVA-stimulated DC), the proliferation of CD34+ stem cells and
      generation of clonogeneic cells were augmented in correspondence with the
      concentration of DCs. After contact coculture with DCs, the proliferation of
      CD34+ stem cells and generation of clonogeneic cells were more significant than
      that in noncontact cultures. Moreover, when cultured with DCs or supernatant of
      DCs, CD34+ progenitor cells were preferentially differentiated to megakaryocytes.
      After coculture with OVA-DCs, markedly greater generation of colony forming units
      granulocyte/macrophages (CFU-GM): colony forming units-megakaryocytes (CFU-MK)
      was found than that in coculture with unstimulated DCs. Pretreatment of DC with
      antibodies to thrombopoietin (TPO), interleukin (IL) -6, IL-12, or anti-mouse
      intercellular adhesion molecule-1 (ICAM-1) could inhibit the ability of DCs to
      support the generation of CFU-GM, CFU-MK. After transplant with BM cells and DCs,
      the number of peripheral platelets of the recipients increased significantly and,
      to a lesser extent, peripheral WBC counts increased. The survival periods were
      significantly prolonged when the lethally irradiated mice were transplanted with
      BM cells combined with DCs or OVA-DCs. High levels of TPO, IL-6, and IL-12 could
      be detectable in the supernatant of DCs, and TPO expression by DCs was further
      confirmed by reverse transcription-polymerase chain reaction analysis and
      intracellular staining with anti-TPO antibody. CONCLUSIONS: We first demonstrated
      that DCs, especially antigen-stimulated DCs, can promote the expansion of
      hematopoietic progenitors and support hematopoiesis, preferentially support
      megakaryopoiesis of BM cells, by expressing soluble factors, including TPO, IL-6,
      IL-12, and by direct cell-to-cell interaction with stem cells in vitro and in
      vivo.

PMID- 11571457
TI  - Accelerated graft arteriosclerosis in cardiac transplants: complement activation
      promotes progression of lesions from medium to large arteries.
AB  - BACKGROUND: A critical role for the terminal components of complement (C5b-C9)
      has been demonstrated previously in acute allograft rejection with the use of C6
      deficient PVG congenic rat strains. The C6 deficiency prevents the formation of
      membrane attack complex (MAC) by C5b-C9. Hearts transplanted from PVG.1A (RT1a)
      rats are rejected acutely (7-9 days) by fully MHC-incompatible C6-sufficient
      PVG.1L (RT11) recipients, but they survive significantly longer in untreated C6
      deficient PVG.1L recipients (19 to >60 days). METHODS: To investigate the
      contribution of MAC to chronic rejection and accelerated graft arteriosclerosis
      (AGA) in long-term cardiac allografts, hearts were transplanted heterotopically
      from PVG.1A donors to C6-sufficient and C6-deficient PVG.1L hosts that were
      treated with cyclosporine 15 mg/kg/day for 14 days after cardiac grafting.
      Alloantibody responses in hosts were measured by flow cytometry at 4, 8, 12, and
      16 weeks after transplantation. Vigorously contracting grafts were removed at 60
      days (n=5) and at 90-128 days (n=12) after surgery for morphological evaluation.
      Computerized planimetry measurements were made in complete cross-sections of
      grafts on all assessable arteries larger than 16 microns in diameter. RESULTS:
      The survival of most (six of seven) cardiac allografts in C6-deficient recipients
      was prolonged by cyclosporine treatment to greater than 90 days. In contrast, 14
      of 25 hearts that were transplanted to C6-sufficient recipients were rejected
      between 21 and 84 days with severe vascular injury. AGA, defined as smooth muscle
      cells forming a neointima inside the internal elastic lamina and luminal
      compromise, affected a greater percentage of arteries in C6-sufficient than in C6
      deficient recipients. AGA developed earlier and more frequently in arteries of
      medium (<100 micron) diameter than those of large diameter in both C6-sufficient
      and C6-deficient recipients. Serial sections demonstrated the lesions in medium
      arteries to be located adjacent to the smooth muscle sphincters at the junction
      of arteriolar branches. CONCLUSIONS: These results demonstrate that MAC promotes
      the pathogenesis of AGA in long-term cardiac allografts.

PMID- 11571458
TI  - Real-time polymerase chain reaction analysis reveals an evolution of cytokine
      mRNA production in allograft acceptor mice.
AB  - BACKGROUND: The relative contribution of pro-inflammatory and anti-inflammatory
      cytokines in promoting the rejection or acceptance of experimental cardiac
      allografts remains controversial. We hypothesized that the posttransplantation
      induction of a new immune response to graft alloantigens at a distant delayed
      type hypersensitivity (DTH) site would force the immune system to reveal its
      current disposition toward graft alloantigen as it initiates the new immune
      response. Thus, we should be able to monitor the evolution of the immunologic
      relationship between allograft recipients and their grafts at any time
      posttransplantation by challenging the recipient for DTH responses to donor
      alloantigen and evaluating the cytokine profiles displayed at the DTH site.
      METHODS: We have used the sensitive and quantitative technique of real-time
      polymerase chain reaction to evaluate the patterns of donor alloantigen-induced
      cytokine mRNA production for interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL
      10, and transforming growth factor (TGF)-beta. We evaluated cytokine mRNA
      expression in cardiac allografts and in donor alloantigen-challenged DTH sites in
      mice that have either accepted or rejected cardiac allografts. RESULTS: We
      observed the following. (1) Normal hearts and pinnae exhibited detectable
      baseline production of cytokine mRNAs: TGF-beta>IFN-gamma=IL-10>IL2->IL-4. (2)
      Both the accepted and rejecting cardiac allografts produced increased amounts of
      all cytokine mRNAs tested and displayed few quantitative differences in cytokine
      mRNA production. Notably, accepted allografts displayed enhanced IL-10 mRNA
      production on day 7 posttransplantation, but not on day 60 posttransplantation
      and reduced IFN-gamma mRNA production on day 60, but not day 7. (3) There was a
      high degree of variability in production levels among the various cytokine mRNAs,
      both for background levels and for allograft-stimulated levels. (4) Donor
      reactive DTH sites of allograft rejector mice displayed a broad array of cytokine
      mRNAs, whereas the DTH sites of allograft acceptor mice displayed only IL-4 mRNA
      production. (5) Provision of exogenous TGF-beta or IL-10 at a DTH challenge site
      of allograft rejector mice caused a shift in the cytokine mRNA profile that
      minimized IFN-gamma and IL-2 mRNA production but spared IL-4, IL-10, and TGF-beta
      mRNA production. CONCLUSIONS: A broad array of cytokine mRNAs may be stockpiled
      for future use in cardiac allografts, regardless of whether the grafts will be
      accepted or rejected. This stockpile is continuously replenished for as long as
      the graft survives, thereby obscuring any changes in immune disposition of the
      graft recipient toward graft alloantigens. However, such changes can be revealed
      by challenge with donor alloantigens at a distant site (DTH challenge). In
      allograft acceptor mice, this disposition evolves from pro-inflammatory to anti
      inflammatory.

PMID- 11571459
TI  - Selective inhibition of IL-2 gene expression by IL-2 antisense oligonucleotides
      blocks heart allograft rejection.
AB  - PURPOSE: We tested the effects of selective inhibition of interleukin (IL)-2 gene
      expression by IL-2 antisense oligonucleotide (oligo) with phosphorothioate
      (PS)/phosphodiester (PD)/2'-methoxyethyl (ME) modifications (17359) on T-cell
      function and the survival of heart allografts in mice. METHODS: The PS- (17328)
      or PS/PD/ME- (17359) IL-2 oligo was electroporated to mouse T cell lymphoma cells
      (TIB 155) stimulated with concanavalin A (Con A). Expression of IL-2 was analyzed
      by an ELISA spot assay and a reverse transcript polymerase chain reaction method.
      C3H (H-2k) mice transplanted with BALB/c (H-2d) heart grafts were treated i.v.
      with a 7-day osmotic pump with 20 mg/kg 17359 alone or in combination with
      sirolimus (SRL). RESULTS: In comparison with untreated controls, 500 to 2000 nM
      17328 inhibited IL-2 protein production by 21.8% to 47.2%, whereas 500 to 2000 nM
      17359 did so by 35.5% to 83.5% (both P<0.001). In vivo, 20 mg/kg 17359 prolonged
      survivals to a mean survival time (MST) of 18.3+/-2.6 days (P<0.001) in
      comparison with only 8.2+/-0.8 days in untreated controls. Although 0.2 mg/kg SRL
      alone produced a MST of 18.8+/-6.0 days (P<0.01), addition of 20 mg/kg 17539
      synergistically extended survivals to 54.3+/-12.1 days (P<0.001). As expected, IL
      2 mRNA, but not IL-7, IL-9, or IL-15 mRNA, was reduced in allografts from
      recipients treated with 17359 compared with untreated controls. Lymph node cells
      from the same recipients displayed reduction in proliferative response to donor
      alloantigen and in generation of alloantigen-specific cytotoxic T cells.
      CONCLUSION: Selective inhibition of IL-2 mRNA in vivo inhibits T-cell function
      and extends allograft survival.

PMID- 11571460
TI  - HLA-C mismatches induce strong cytotoxic T-cell reactivity in the presence of an
      additional DRB/DQB mismatch and affect NK cell-mediated alloreactivity.
AB  - BACKGROUND: The functional relevance of HLA-C mismatches in an alloresponse is
      still much debated, putting into doubt the relevance of matching for this antigen
      in selection of an allogeneic bone marrow donor. In addition to presenting
      peptides to T cells, HLA-C also functions as a ligand for killing inhibitory
      receptors (KIRs) on natural killer (NK) cells. In the current study we provide an
      in vitro basis to address the question of whether mismatches for this antigen are
      a risk factor for acute graft-versus-host disease (GVHD). METHODS AND RESULTS: By
      analysis of cytotoxic and helper T-lymphocyte precursor frequency (CTLp-f and
      HTLp-f) in 153 pairs, we are able to show that isolated HLA-C mismatches appear
      less immunogenic than do isolated HLA-A mismatches. Strikingly, the presence of
      an HLA-C mismatch next to a HLA-DRB or HLA-DQB mismatch leads to a synergistic
      increase in CTLp-f outcome. Moreover, we are the first to show that absence of a
      single inhibitory epitope as a result of an HLA-C mismatch can be sufficient to
      induce NK mediated alloreactivity, that is, kill and proliferate. CONCLUSIONS: We
      conclude that, in most cases, isolated HLA-C mismatches may be acceptable with
      respect to T-cell-mediated alloreactivity; however, the presence of a strong
      helper epitope (DR/DQ mismatch) appears sufficient to overcome the low
      immunogenicity of HLA-C. HLA-C mismatches that affect KIR epitopes, can induce NK
      mediated alloreactivity. This suggests that, in HLA-A-, -B-, -DR-, and -DQ
      matched patients, NK cells may play a role in the induction and development of
      acute GVHD.

PMID- 11571461
TI  - Th2 cytokine profile in infants predisposes to improved graft acceptance after
      liver transplantation.
AB  - BACKGROUND: The T helper cell type 1 (Th1) cytokines interleukin (IL)-2 and
      interferon (IFN)-gamma are mediators of acute graft rejection after liver
      transplantation and Th2 cytokines, such as IL-4 and IL-10, may have a protective
      role and correlate with graft acceptance. To test the hypothesis that infants
      aged <1 year have an immunological advantage with regard to graft acceptance
      because of a partially immature immune system with a physiological balance toward
      a Th2 cytokine profile, we conducted the present study. METHODS: We compared the
      T helper serum cytokine profiles in 105 infants and children after liver
      transplantation with or without acute graft rejection and analyzed the normal age
      distributed concentrations of T helper cytokines in 51 healthy controls. RESULTS:
      The incidence of acute graft rejection was as follows: 0 to 12 months, 26.8%; 1
      to 3 years, 40.0%; and >3 years, 71.8%. There was a significantly lower incidence
      of acute rejection in infants 0 to 12 months of age compared with children >1
      year (11/41 vs. 38/64; P=0.001). In healthy infants, significant increasing Th1
      cytokine concentrations and decreasing Th2 cytokine concentrations were found
      with increasing age. Patients with acute rejection had significantly higher
      values of Th1 cytokines compared with nonrejecting subjects, who had
      significantly higher concentrations of Th2 cytokines. A longitudinal analysis of
      serum cytokines from patients showed that changes of the cytokine patterns in the
      follow-up did not differ significantly from preoperative values, except in the 4
      weeks posttransplant. CONCLUSIONS: We conclude from the data that the
      physiological balance toward a Th2 cytokine profile of infants in the first
      months of life predisposes to improved graft acceptance. Transplantation of
      children with biliary atresia as early as possible, avoiding Th1 stimulation by
      recurrent infections and vaccinations, may have a positive impact on overall
      tolerance.

PMID- 11571462
TI  - Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to acute
      allograft rejection.
AB  - BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA4) has been shown to play a
      critical role in the down-regulation of the immune response. We retrospectively
      examined the association between acute rejection and two polymorphisms in the
      CTLA4 gene, the dinucleotide (AT)n repeat polymorphism in exon 3 and the single
      nucleotide polymorphism A/G at position 49 in exon 1, in a cohort of liver and
      kidney transplant recipients. METHODS AND RESULTS: A total of 207 liver and 167
      renal transplant recipients were analyzed. In the case of the (AT)n repeat
      polymorphism we found an increased incidence of acute rejection in association
      with allele 3 and 4 in both liver and kidney (P=0.002 and 0.05, respectively). In
      addition, in liver transplant recipients, allele 7 was associated with acute
      rejection independent of ethnicity (P<0.05). Allele 1 was less frequently
      observed in African American as compared with Caucasian liver and kidney
      transplant recipients, with a frequency of 33.8% and 69%, respectively
      (P<0.0001). Those patients with allele 1 had a tendency toward a lower rate of
      rejection at 42% versus 57.8% (P=0.058), suggesting a potential protective effect
      of allele 1. Analysis of the A/G single nucleotide polymorphism demonstrated no
      association between either allele and the incidence of acute rejection in the
      patients studied. CONCLUSION: These initial observations provide the necessary
      basis to further investigate the risk stratification of transplant recipients
      based on specific CTLA4 gene polymorphisms.

PMID- 11571463
TI  - Time-dependent risk factors influencing the long-term outcome in living renal
      allografts: donor age is a crucial risk factor for long-term graft survival more
      than 5 years after transplantation.
AB  - BACKGROUND: Most investigations have revealed that the improvement in early graft
      survival has not resulted in a corresponding improvement in long-term graft
      survival. The risk factors for long-term graft survival should be clarified.
      METHODS: A single-center experience of 1100 consecutive renal transplant
      recipients who received kidneys from living donors from 1983 to 1998 was reviewed
      to clarify the time dependency of risk factors for long-term graft survival. We
      examined various possible risk factors, including HLA-AB and -DR mismatches, ABO
      blood group incompatibility, graft weight, donor age and sex, recipient age and
      sex, and the presence or absence of acute rejection by using the time-dependent,
      nonproportional Cox's hazards model. RESULTS: Acute rejection episode, donor age,
      HLA-AB 4-antigen mismatches, ABO-incompatible transplantation, smaller kidney
      weight compared with the patient's body weight (Kw/Bw ratio less than 2.67), and
      transplantation from an unrelated living donor were risk factors for long-term
      graft outcome. Multivariate analysis for time-dependent risk factors showed that
      donor age of more than 60 years was the most important risk factor for long-term
      graft failure after 5 years posttransplantation (hazard ratio: 2.57). In
      contrast, acute rejection, ABO incompatibility, and nonrelated donors were
      significant risk factors for short-term graft failure within 5 years after kidney
      transplantation (hazard ratios: 2.68, 1.57, and 1.69, respectively). CONCLUSIONS:
      Donor age of more than 60 years was a crucial risk factor affecting long-term
      graft survival. In contrast, acute rejection, ABO incompatibility, and nonrelated
      donors were significant risk factors for short-term graft failure.

PMID- 11571464
TI  - Gene expression analysis in human renal allograft biopsy samples using high
      density oligoarray technology.
AB  - BACKGROUND: High-density oligoarray technology is a novel method for screening
      the expression of thousands of genes in a small tissue sample. Oligoarray
      analysis of genes expressed during human renal allograft rejection has not been
      reported previously. METHODS: Seven human renal allograft biopsies with
      histologic evidence of acute cellular rejection and three renal allograft
      biopsies without evidence of rejection (control) were analyzed for the expression
      of 6800 human genes using high-density oligoarrays (GeneChip, Affymetrix, Santa
      Clara, CA). Quantitative expression of gene transcripts was determined and a
      comparison analysis between acute rejection and control biopsy samples was
      performed. Up-regulation of a specific gene transcript during acute rejection was
      considered to be significant if transcript abundance increased fourfold or more
      relative to control biopsy samples. RESULTS: Comparison analysis revealed that
      between 32 and 219 gene transcripts are up-regulated (>fourfold) during acute
      rejection. Of these transcripts, only four (human monokine induced by interferon
      gamma, T-cell receptor active beta-chain protein, interleukin-2 stimulated
      phosphoprotein, and RING4 (a transporter involved in antigen presentation)) were
      consistently up-regulated in each acute rejection sample relative to at least two
      of three control biopsy samples. Six other genes were up-regulated in six of
      seven acute rejection samples. These were interferon-stimulated growth factor-3,
      complement factor 3, nicotinamide N-methyltransferase, macrophage inflammatory
      protein-3beta, myeloid differentiation protein, and CD18. Only two gene
      transcripts were down-regulated in five of seven acute rejection samples.
      Significant up-regulation of cytotoxic T-cell effector molecules, previously
      reported as markers of acute renal rejection in humans, was not detected.
      CONCLUSIONS: High-density oligoarray technology is useful for screening gene
      expression in transplanted tissues undergoing acute rejection. Because this
      method does not rely on a priori knowledge of which genes are involved in acute
      rejection, it is likely to yield novel insights into the mechanisms and diagnosis
      of rejection.

PMID- 11571466
TI  - Treatment of multiple aneurysms of the splenic artery after liver transplantation
      by percutaneous embolization and laparoscopic splenectomy.
AB  - A high incidence of aneurysms of the splenic artery is found in liver transplant
      patients. Their significance is related to the risk of rupture, particularly in
      the postoperative period. Classically, their management is surgical, with
      ligation or resection of the aneurysmal arterial segment with or without
      splenectomy, depending on the location of the aneurysm. Recently, laparoscopy and
      percutaneous embolization have appeared as alternative treatment options. We
      describe here the treatment of multiple aneurysms of the splenic artery in a
      patient who had undergone liver transplantation 10 years earlier. She was treated
      with percutaneous embolization of the aneurysms followed by laparoscopic
      splenectomy. To our knowledge, this is the first report of laparoscopic
      splenectomy following liver transplantation. It demonstrates that prior liver
      transplantation does not represent an absolute contraindication to minimally
      invasive surgery.

PMID- 11571465
TI  - An essential role for natural killer cells in augmentation of allograft survival
      mediated by donor spleen cells.
AB  - BACKGROUND: Previous studies have shown that skin allograft survival can be
      augmented by the administration of donor spleen or donor bone marrow in
      antithymocyte serum (ATS) treated recipients. Because natural killer cells (NK)
      have been reported to possess immunoregulatory properties, we investigated
      whether the ability of donor spleen or bone marrow cells to enhance allograft
      survival was dependent on the presence of donor NK cells. METHODS: Recipient
      (C57BL/6 x A/J)F1 strain mice (H2 haplotypes Kb/k, Ab/k, E-/k, Db/d) were treated
      with ATS on days -1 and +2 relative transplantation of a C3H (H-2k) skin
      allograft. On day +7, each recipient was randomly assigned to one of the
      following groups that received i.v. donor C3H cell infusions via the tail vein:
      1) 5.0x10(7) wild-type donor spleen cells (SPC); 2) 5.0x10(7) spleen cells from
      C3H/HeJ-Lystbg-2J/+ mice (commonly called beige mice and have selectively
      impaired NK cell function); 3) 2.5x10(7) wild-type donor bone marrow cells (BMC);
      4) 2.5x10(7)beige C3H bone marrow cells; and 5) no donor cell infusion (ATS
      controls). In another experiment, each recipient was randomly assigned to one of
      the following groups that received injections of: 1) 4.75x10(7) spleen cells
      depleted of NK cells; 2) 2.5x10(6) purified splenic NK cells; 3) a coinfusion of
      5.0x10(7) beige spleen cells and 2.5x10(6) purified wild-type splenic NK cells.
      RESULTS: Recipients infused with wild-type SPC exhibited significant augmentation
      of allograft survival compared with ATS controls. However, graft survival was
      reduced in recipients that were infused with spleen cells from beige mice
      compared with recipients infused with wild-type SPC (median survival time (MST):
      38 vs. 92 days, P=0.02). In contrast, infusions of beige BMC augmented allograft
      survival as well as wild-type BMC (MST: 47 vs. 49 days, P=0.76). Furthermore, the
      ability of wild-type SPC to augment allograft survival was abrogated by the
      depletion of NK cells (MST=92 vs. 34 days, respectively, P=0.005). The co
      infusion of beige SPC and purified splenic NK cells enhanced allograft survival
      as well as wild-type SPC (MST=56 days, P=0.65). Finally, recipients infused with
      purified NK cells did not experience increased graft survival compared to
      recipients that received no infusion (MST=29 vs. 33 days, respectively, P=0.6).
      CONCLUSIONS: Donor splenic NK cells are necessary, but not sufficient, for the
      extension of graft survival by infusion of donor splenocytes, suggesting that
      they may work in concert with another cell-type. In contrast, the extension of
      graft survival by donor bone marrow does not depend on the presence of donor NK
      cells.

PMID- 11571467
TI  - Kidney transplantation unraveling Wolfram syndrome: a case report.
AB  - BACKGROUND: In Wolfram syndrome insulin-dependent diabetes is associated with a
      multisystem neurodegenerative disorder. There are no prior reports of kidney
      transplantation in patients with Wolfram syndrome. METHODS: Kidney
      transplantation was undertaken in a child with dysplastic kidneys, sensorineural
      hearing impairment and bilateral optic atrophy-a combination of features
      insufficient to define Wolfram syndrome. RESULTS: After the procedure diabetes
      mellitus, diabetes insipidus and urinary bladder dysfunction emerged, thereby
      revealing Wolfram syndrome. CONCLUSIONS: We discuss the etiology of our patient's
      postoperative events, and conclude that kidney transplantation may expose dormant
      manifestations-or aggravate existing manifestations-of Wolfram syndrome.

PMID- 11571468
TI  - Cavoportal hemitransposition in liver transplantation.
AB  - Over the last decade a large number of patients with portal vein thrombosis have
      undergone successful liver transplantation. In most of these patients, simple
      modifications in vascular reconstruction techniques are adequate. However,
      anastomosis of the donor portal vein may not be possible in the presence of
      extensive portal and superior mesenteric venous thrombosis and in the absence of
      any other large tributary of the portal venous system. Cavoportal
      hemitransposition has been described as a salvage technique under these
      circumstances. We report a 43-year-old patient who underwent such a procedure and
      remains well 1 year later. We review the literature and discuss the implications
      of cavoportal hemitransposition.

PMID- 11571470
TI  - T-cell lymphoma with eosinophilia of donor origin occurring 12 years after
      allogeneic bone marrow transplantation for myeloma.

PMID- 11571471
TI  - Must kidney donation by living strangers be nondirected?

PMID- 11571472
TI  - Arterioenteric fistula due to cytomegalovirus infection after pancreas
      transplantation.

PMID- 11571473
TI  - Oral ulcerations in a renal transplant recipient: a mycophenolate mofetil-induced
      complication?

PMID- 11571474
TI  - Quality of life after transplantation for patients with diabetes and renal
      dysfunction.

PMID- 11571476
TI  - Re: impact of transplantation on quality of life in patients with diabetes and
      renal dysfunction by Gross et al. Transplantation 2000: 70(12): 1736.

PMID- 11571477
TI  - Outcome after transplantation of young patients with systemic lupus
      erythematosus: a report of the North American pediatric renal transplant
      cooperative study.
AB  - BACKGROUND: The risk of progressing to end-stage renal disease in children with
      lupus glomerulonephritis is 18% to 50%. Published reports of transplantation
      secondary to end-stage renal failure in adult patients with systemic lupus
      erythematosus (SLE) demonstrate equivalent patient and graft survival. The
      purpose of this analysis is to compare patient and graft outcomes of pediatric
      SLE renal transplant recipients with an age-, race-, and gender-matched control
      group. METHODS: A retrospective analysis of the North American Pediatric Renal
      Transplant Cooperative Study (NAPRTCS) database identified 100 renal transplants
      performed in 94 young SLE patients. A control group of 470 children having
      received 501 renal transplants was identified. RESULTS: The SLE cohort was
      primarily female (82%), non-Caucasian (61%), adolescents and differed from the
      control group in being less likely to be preemptively transplanted, in receiving
      longer pretransplant dialysis, and in being likely to have received more than
      five pretransplant transfusions. After transplantation, there were no differences
      seen in patient survival at 3 years (89% vs. 95%, SLE vs. control) or in overall
      graft failure rates (31% vs. 29%, SLE vs. control). There was a trend toward
      poorer graft survival in non-white SLE patients receiving living donor grafts
      compared with white SLE patients. An increased graft failure rate was seen among
      those SLE cadaveric transplant recipients receiving peritoneal dialysis before
      transplant compared with controls and compared with SLE patients receiving
      hemodialysis. No differences were seen in rates of acute tubular necrosis or
      overall acute rejection incidence, although there was a significant increase in
      the percentage of living donor SLE patients who experienced greater than four
      rejection episodes. There were nonsignificant trends toward increased graft loss
      due to patient death with a functioning graft as well as increased mortality
      secondary to infection in the SLE patients. CONCLUSIONS: The results of renal
      transplantation in young SLE patients are comparable to those seen in an age-,
      race- and gender-matched control group. The similar patient and graft survival is
      seen despite the SLE patients having an underlying disease with multiorgan
      involvement and despite receiving immunosuppression for potentially prolonged
      periods before transplantation. No outcome differences were seen except for an
      unexplained increase in the incidence of recurrent rejections (> or =4) in the
      living donor SLE patients as well as increased graft failure rate in those
      patients receiving cadaveric renal transplants after a period of peritoneal
      dialysis. The nonsignificant trends toward increased graft failures in non-white
      SLE patients receiving living donor grafts, increased graft loss secondary to
      death with a functioning graft, as well as the increased mortality due to
      infection deserve recognition and further study.

PMID- 11571478
TI  - High-density lipoprotein: epidemiology, metabolism, and antiatherogenic effects.

PMID- 11571479
TI  - Inhibition of neuronal nitric oxide reduces heart rate variability in the
      anaesthetised dog.
AB  - In the vagally intact anaesthetised dog, we have investigated the role of nitric
      oxide (NO) on a normal sinus arrhythmia using an inhibitor of neuronally released
      NO, 1-(2-trifluoromethylphenyl) imidazole (TRIM). The mean and S.D. of the R-R
      interval was used to describe mean heart rate and heart rate variability,
      respectively. TRIM (0.8 mg I.C.) injected into the sinus node artery increased
      the mean heart rate slightly but reduced heart rate variability 3-fold from a
      control of 790 +/- 124 ms (mean +/- S.D.; n = 5) to 666 +/- 36 ms (P < 0.01
      Student's paired t test, n = 5). These results suggest that neuronally released
      NO may have a vagal facilitatory role in the maintenance of sinus arrhythmia in
      the normal heart.

PMID- 11571480
TI  - Adrenomedullin and proadrenomudullin N-terminal 20 peptide (PAMP) are present in
      human colonic epithelia and exert an antimicrobial effect.
AB  - The hypotensive and vasorelaxing peptides adrenomedullin (AM) and its gene
      related peptide, proadrenomedullin N-terminal 20 peptide (PAMP), were found to be
      distributed on the surface of the colonic mucosa. AM and PAMP showed dose
      dependent antimicrobial activity against E. coli. The results suggest that the
      novel vasoactive peptides AM and PAMP play an important role in mucosal defence.

PMID- 11571481
TI  - Corticospinal inhibition appears normal in patients with chronic fatigue
      syndrome.
AB  - The pathogenesis of chronic fatigue syndrome (CFS) remains unknown. Thresholds
      and latencies of motor evoked potentials (MEPs) in response to transcranial
      magnetic stimulation (TMS) are normal but intracortical inhibition has not been
      investigated. Eleven patients with CFS were compared with 11 control subjects.
      Each patient completed a questionnaire using visual analogue indices of pain,
      fatigue, anxiety and depression. Subjects released a button to initiate simple
      (SRTs) and choice reaction time (CRTs) tasks; for each task, movement times were
      measured between release of the initiation button and depression of a second
      button 15 cm away. Subjects held a 10 % maximum voluntary contraction in the
      thenar muscles of their dominant hand while TMS was applied to the motor cortex;
      the duration and extent of inhibition of surface electromyographic (EMG) activity
      were assessed at stimulus strengths above and below the threshold for MEPs.
      Patients had significantly (P < 0.05) higher mean indices of fatigue than of
      pain, anxiety or depression. Mean (+/- S.E.M.) SRTs (but not CRTs) were longer in
      patients (309 +/- 45 ms) than in controls (218 +/- 9 ms). Movement times were
      longer in patients for both SRTs and CRTs. TMS thresholds, expressed as a
      percentage of the maximum stimulator output, were not significantly (P > 0.05)
      different in both groups for both MEPs (patients, 34 +/- 3%; controls, 36 +/- 3%)
      and inhibition of voluntary contraction (patients, 29 +/- 2%; controls, 34 +/-
      4%). The duration and extent of inhibition did not differ significantly between
      groups at any stimulus strength. The pattern of change in duration and extent of
      inhibition with increasing stimulus intensity was no different in the two groups.
      The duration and extent of corticospinal inhibition in patients with CFS did not
      differ from controls, adding further evidence to the notion that the feeling of
      fatigue and the slowness of movement seen in CFS is not manifest in corticospinal
      output pathways.

PMID- 11571482
TI  - A model for an Ascaris muscle cell.
AB  - Muscle cells in the nematode Ascaris suum undergo bouts of oscillation in the
      behaving worm, these being correlated with progressing waves of contraction along
      the body of the worm. The bouts have three time scales: a rough period of 7-20 s,
      10-20 short bursts of spikes within a bout, and three to eight spikes per burst.
      This paper has two aims: showing that there is consistency between measurements
      of individual currents and measurements on whole muscle cells, and creating a
      building block to eventually explain the locomotion in this 'simple' system. A
      realistic model for a single Ascaris suum muscle cell is developed using existing
      data from experiments which have established the types of ionic currents in the
      muscle cell and many of their kinetic properties. Numerical simulations are
      carried out. The model cell reproduces the two shorter time scales present. It
      has some robustness with regard to parameter changes, but also allows for the
      different numbers of spikes per burst seen in recordings from muscle cells. The
      third time scale, the length of a bout, may originate from some system effect, a
      combination of neural and stretch effects and possibly a secondary effect of the
      calcium-activated chloride channel.

PMID- 11571483
TI  - Inotropic actions of protein kinase C activation by phorbol dibutyrate in guinea
      pig isolated ventricular myocytes.
AB  - The mechanisms which underlie the inotropic actions of phorbol dibutyrate (PDBu),
      a synthetic compound which can directly activate protein kinase C (PKC), were
      investigated in guinea-pig isolated ventricular myocytes. Exposure of cells to
      PDBu (10(-7) M) reduced myocyte contraction amplitude to 46 +/- 3% of control (n
      = 8; P < 0.05) with an associated shortening in action potential duration (action
      potential duration at 90% repolarisation (APD90) was reduced to 83 +/- 1% of
      control; P < 0.05). The negative inotropic actions of PDBu and the shortening in
      action potential duration were abolished in the presence of a selective PKC
      inhibitor, Ro31-8220. Calcium transients (constructed from calcium-activated tail
      currents following interruption of action potentials by voltage clamp to -70 mV)
      were reduced following exposure to 10(-7) M PDBu by 38 +/- 2% (n = 9, P < 0.05).
      L-type calcium currents were not significantly altered following exposure to 10(
      7) M PDBu (98 +/- 2% of control; P > 0.05). In contrast, delayed rectifier
      potassium currents (I(K)) were enhanced to 154 +/- 8% of control (n = 7; P <
      0.05) by 10(-7) M PDBu. This enhancement of I(K) may contribute to the observed
      shortening in action potential duration observed following exposure to PDBu under
      the conditions of our experiments. When the action potential configuration was
      maintained throughout the experiment by applying a voltage-clamp waveform, 10(-7)
      M PDBu still reduced contraction amplitude to 57 +/- 3% of control (P < 0.05).
      Exposure to 10(-7) M PDBu also suppressed spontaneous activity (both spontaneous
      potential fluctuations induced by the beta-adrenergic agonist isoprenaline (40
      nM), and transient inward currents induced by the cardiac glycoside ouabain (1
      microM) under voltage clamp). It therefore appears that the reduction in myocyte
      contraction amplitude induced by exposure to PDBu may result in part through
      mechanisms independent of action potential shortening, which may include direct
      actions of protein kinase C on the function of the sarcoplasmic reticulum (SR)
      calcium store and/or on contractile proteins (though action potential shortening
      would be expected to cause a further decrease as a consequence of reduced calcium
      loading of the SR). The reduction of spontaneous activity caused by PDBu may also
      result from changes in the function of the SR store mediated by protein kinase C.

PMID- 11571484
TI  - The presence of NHE1 and NHE3 Na+-H+ exchangers and an apical cAMP-independent Cl
      channel indicate that both absorptive and secretory functions are present in
      calf gall bladder epithelium.
AB  - We investigated the transport systems that can sustain Na+ and Cl- movements
      across bovine gall bladder epithelium, focusing on the Na+-H+ exchanger (NHE)
      family and chloride conductive pathways. Experiments conducted using the
      fluorescent probe acridine orange (AO) with brush-border membrane vesicles (BBMV)
      or vesicles obtained from the total epithelium (EMV) demonstrated the presence of
      a Na+-H+ exchange in both preparations. The use of specific inhibitors indicated
      the presence of an apical NHE3 exchanger and a NHE1 isoform which should reside
      in the basolateral membrane. Using reverse transcriptase (RT) PCR, we identified
      cDNA fragments corresponding to the NHE1, NHE3, Cl--HCO3- (AE2a) transporters and
      to the CFTR channel. Using the patch-clamp technique, we investigated Cl-
      conductances on cultured epithelial cells. We found a 5 pS Cl- channel with a
      voltage-independent open probability, insensitive to stilbenes (SITS), Zn2+ and
      cAMP. The results suggest that absorption and secretion coexist in calf gall
      bladder epithelium. A Na+-H+-Cl--HCO3- double exchange may, at least partially,
      sustain the absorptive function, and a Cl- apical conductive pathway may be
      involved in secretion. The conductance we observed does not seem to be cAMP
      regulated, unlike other mammalian gall bladders.

PMID- 11571486
TI  - Interstitial adenosine concentration in rat red or white skeletal muscle during
      systemic hypoxia or contractions.
AB  - Interstitial adenosine concentrations in red soleus (SL) or white extensor
      digitorum longus (EDL) muscles of anaesthetised rats were determined using
      microdialysis and HPLC. Systemic hypoxia was induced by ventilating the animals
      with 10% oxygen in nitrogen for 15 min: arterial PO2 decreased from 111.8 +/-
      10.9 to 42.2 +/- 4.3 mmHg (n = 4; P < 0.01) and mean systemic arterial blood
      pressure from 97.6 +/- 4.9 to 59.0 +/- 3.6 mmHg (n = 22; P < 0.001). The
      interstitial adenosine concentration was not significantly changed from its
      control values of 294 +/- 44 nM (n = 20) in EDL and 302 +/- 36 nM (n = 20) in SL
      during hypoxia or the recovery period. The interstitial lactate concentration did
      not change in the early part of the hypoxia but increased from 1.0 +/- 0.2 to 1.4
      +/- 0.3 mM (n = 6; P < 0.05) in SL and from 2.0 +/- 0.4 to 2.4 +/- 0.4 mM (n = 6;
      P < 0.05) in EDL during the later part of the hypoxia, and remained elevated in
      the recovery period. Muscle contractions (2 Hz for 15 min) produced a transient
      increase in the interstitial adenosine concentration of SL from 150 +/- 35 to 244
      +/- 75 nM (n = 10; P < 0.05) during the first 5 min of stimulation. In EDL the
      interstitial adenosine concentration increased from 145 +/- 50 to 435 +/- 144 nM
      (n = 10; P < 0.05) in the later part of the contraction and remained elevated in
      the early part of the recovery period. These data suggest that: (i) in systemic
      hypoxia adenosine does not appear in the interstitial space, which rules out its
      release from skeletal muscle, although it may be formed by the vascular tissues
      in this condition; (ii) adenosine is formed in the interstitial space of skeletal
      muscle during muscle contractions; (iii) there is slow clearance of adenosine
      from the interstitial space of white muscle, perhaps due to the low vascularity
      of the tissue.

PMID- 11571485
TI  - Role of Rho-associated protein kinase in tone and calcium sensitivity of
      cannulated rat mesenteric small arteries.
AB  - The regulation of vascular tone includes modulation of contractile element
      calcium sensitivity. We tested the involvement of the Rho-associated protein
      kinase p160ROCK in tone and calcium sensitivity of cannulated rat mesenteric
      small arteries. These vessels developed basal tone and showed myogenic responses
      upon pressure steps, resulting from an increase in calcium in combination with a
      high contractile element calcium sensitivity. Y-27632, believed to be a specific
      p160ROCK inhibitor, caused concentration-dependent inhibition of basal tone, with
      near full inhibition at 3 microM. At this concentration, myogenic responses were
      absent and stepwise pressure elevation resulted in severe vascular distension. Y
      27632 did not affect pressure-induced changes in intracellular calcium but rather
      reduced pressure-induced as well as phenylephrine-induced calcium sensitisation.
      Thus in the presence of the blocker, for a given calcium concentration, tone was
      greatly reduced, and the divergence in sensitivity between pressure and
      phenylephrine as stimuli on the one hand and potassium on the other disappeared.
      K+ (125 mM) and ionomycin still caused contraction in the presence of the
      p160ROCK blocker. These data show that in pressurised small arteries the Rho
      p160ROCK pathway is active in the absence of vasoconstrictors, keeping the
      vessels in a state of high calcium sensitivity and basal tone.

PMID- 11571487
TI  - Eccentric contractions affect muscle membrane phospholipid fatty acid composition
      in rats.
AB  - This study investigated if prior eccentric contractions, and thus mechanical
      strain and muscle damage, exert an effect on the muscle membrane phospholipid
      fatty acid composition in rats, and whether a possible effect could be attenuated
      by dietary supplements. Twenty-three rats were randomised to three groups who
      received chow with added fish oil (n = 8), vitamin C (n = 8) or no supplement (n
      = 7). After 3 weeks of feeding, calf muscles on one side were stimulated
      electrically during anaesthesia causing eccentric contractions. Two days later
      the white gastrocnemius, a part of the stimulated calf muscle, was excised from
      both legs. In the muscles stimulated to contract eccentrically, compared to the
      control muscles, the proportion of arachidonic acid, C20:4,n-6 (17.7 +/- 0.6;
      16.4 +/- 0.4% of total fatty acids, respectively) and docosapentanoeic acid,
      C22:5,n-3 (2.9 +/- 0.1 and 2.7 +/- 0.1% of total fatty acids, respectively) was
      uniformly higher across groups (P < 0.02) with no differences between diet
      groups. The proportion of long chain polyunsaturates was also significantly
      higher in the eccentrically contracted (39.9 +/- 0.6% of total fatty acids)
      compared to the control leg (38.2 +/- 0.6% of total fatty acids; P < 0.01). In
      contrast no differences were observed in the fatty acid composition of the
      triacylglycerols stored within the muscle. Thus one severe bout of eccentric
      contractions modulates the fatty acid composition of the muscle membrane
      phospholipids when compared to a control leg, and supplemental intake of fish oil
      or vitamin C did not attenuate this effect.

PMID- 11571488
TI  - Reflex-elicited increases in female rat parotid protein synthesis involving
      parasympathetic non-adrenergic, non-cholinergic mechanisms.
AB  - Normal rats or rats parasympathetically denervated on one side by cutting the
      auriculo-temporal nerve were maintained on a liquid diet for 1 week. After
      fasting overnight, experimental rats were then offered hard, pelleted food over a
      period of 2 h, while unfed animals served as controls. The reflex-induced
      increase in the [3H]leucine incorporation into trichloroacetic acid-insoluble
      material of the parotid glands following intake of the food in the presence of
      the muscarinic blocker atropine and alpha- and beta-adrenoceptor antagonists was
      greater (104%) than in the absence of the blockers (75%) in normal rats. The
      picture was the same when the innervated glands of rats subjected to unilateral
      parasympathetic denervation were examined. In this case, the protein synthesis
      increased by 108% in the presence of the blockers and by 63% in their absence.
      Analysis of the parasympathetically denervated and contralateral innervated
      glands revealed no support for a cholinergic or adrenergic contribution to this
      response. The increase in protein synthesis in the innervated glands was 86% in
      the rats treated with atropine, whilst it was 76% in those treated with alpha-
      and beta-adrenoceptor antagonists. The protein synthesis in the denervated glands
      increased by 57% in the absence of receptor blockade. Neither atropine (51%), nor
      a- and b-adrenoceptor antagonists (52%), nor a combination of the three blockers
      (55%) affected the response of the denervated glands. A large part of the
      response in the presence of the traditional autonomic receptor blockers was thus
      dependent on the parasympathetic auriculo-temporal nerve. Under natural feeding
      conditions, the parasympathetic non-adrenergic, non-cholinergic (NANC) mechanisms
      are likely to contribute to the synthesis of secretory proteins.

PMID- 11571489
TI  - Renal vascular effects of frusemide in the rat: influence of salt loading and the
      role of angiotensin II.
AB  - We showed recently that post-frusemide (furosemide) natriuresis was associated
      with a major depression of medullary circulation. In the present study, prior to
      administration of frusemide the tubular transport of NaCl was modified by loading
      the animals with 5% saline to elucidate a possible interrelation between the
      tubular and vascular effects of the drug. Moreover, a possible involvement of the
      renin-angiotensin system was examined by pharmacological blockade using
      captopril, an inhibitor of angiotensin converting enzyme (1 mg x kg(-1), I.V.),
      or losartan, a selective inhibitor of angiotensin AT1 receptor (10 mg x kg(-1),
      I.V.). The effects of frusemide (0.25 mg x kg(-1) I.V., then the same dose given
      over 1 h) on renal medullary and cortical circulation (using laser-Doppler
      flowmetry) and renal excretion of sodium (U(Na)V), water and total solutes were
      measured in anaesthetised rats. With no pre-treatment, frusemide decreased the
      medullary flow (36.6 +/- 6.0%) significantly more than the cortical flow (10.1 +/
      1.0%; P < 0.001). The difference between the medulla and cortex was not
      significant in rats which showed high U(Na)V after hypertonic saline loading (2.0
      +/- 0.4 vs. 0.4 +/- 0.1 micromol x min(-1) in non-loaded rats): 21.1 +/- 3.9% and
      15.8 +/- 1.5%, respectively. At very high U(Na)V (9.5 +/- 1.1 micromol x min(-1))
      the post-frusemide decrease in blood flow tended to be smaller in the medulla
      (7.6 +/- 7.7%) than in the cortex (16.2 +/- 2.6%). The fall in medullary blood
      flow was attenuated by pre-treatment with captopril (22.0 +/- 3.3%) and abolished
      by pre-treatment with losartan (2.8 +/- 11.8%). The decrease in cortical blood
      flow was not changed by hypertonic saline or angiotensin II blockers. The
      abolition of the post-frusemide depression of medullary blood flow by previous
      salt loading confirms the proposed link between tubular transport status and
      vasoconstriction. A similar modification of the response by blockade of the renin
      angiotensin system suggests that the system is involved in the mechanism of
      medullary vasoconstriction.

PMID- 11571490
TI  - Effects of pinealectomy on glucagon responsiveness to hypoglycaemia induced by
      insulin injections in fed rats.
AB  - The glucagon response to insulin-induced hypoglycaemia was tested in rats that
      had been pinealectomised (Px), pinealectomised and fitted with melatonin implants
      (Px + MLT), or sham-operated (SO). The glucagon response to hypoglycaemia
      observed in SO rats (216 +/- 27 pg x ml(-1) at baseline versus 397 +/- 35 pg x
      ml(-1) at the hypoglycaemic peak, mean +/- S.D.) was stronger than that in Px
      rats (180 +/- 37 pg x ml(-1) and 229 +/- 21 pg x ml(-1), respectively) and weaker
      than that in Px + MLT rats (256 +/- 19 pg x ml(-1) and 516 +/- 11 pg x ml(-1),
      respectively). Our data indicate that the capacity to release glucagon during
      insulin-induced hypoglycaemia is altered in pinealectomised rats.

PMID- 11571492
TI  - Differential effects of cold exposure on muscle fibre composition and capillary
      supply in hibernator and non-hibernator rodents.
AB  - Changes in the composition of fibre types and the capillary supply of skeletal
      muscle (tibialis anterior) were quantified in rats and hamsters subjected to 8-10
      weeks of cold exposure and reduced photoperiod (10 degrees C, 1 h light-23 h
      dark). Muscle mass decreased in both species (by 12% and 17%, respectively).
      Following acclimation to cold there were no specific changes in fibre cross
      sectional area (FCSA) in rats, whereas in hamsters there was a substantial
      atrophy of Type II, but not Type I fibres. In rat muscle there was little
      difference between the two groups in average capillary to fibre ratio (C:F) (1.76
      +/- 0.15, normothermia, N; 1.69 +/- 0.05, hypothermia, H) and average capillary
      density (CD) (188 +/- 14 mm(-2), N; 201 +/- 12 mm(-2,) H). Similarly, the average
      C:F was unaltered in hamsters (2.75 +/- 0.11, N; 2.72 +/- 0.15, H), although the
      30 % smaller fibre size observed with hypothermia resulted in a corresponding
      increase in average CD, to 1539 +/- 80 mm(-2) (P < 0.01). However, there was a
      coordinated regional adaptation to cold exposure in hamsters resulting in
      capillary rarefaction in the glycolytic cortex and angiogenesis in the oxidative
      core. Following acclimation of rats to cold there was a reduction in the supply
      area of individual vessels (capillary domain), particularly in the cortex (9310,
      N; 8938 microm2, H; P < 0.05). In contrast, hypothermic hamsters showed only a
      small decrease in mean domain area in the cortex (948 microm2, N; 846 microm2, H;
      n.s.) but a marked reduction in the core (871 microm2, N; 604 microm2, H; P <
      0.01). Rats showed little or no change in local capillary supply (LCFR) to fast
      fibres on acclimation to cold, while in hamsters the LCFR of Type IIb fibres
      showed a decrease in the cortex (2.7, N; 2.3, H) and an increase in the core
      (3.0, N; 3.3, H) during acclimation to cold. These data suggest that during a
      simulated onset of winter rats maintain FCSA and capillary supply as part of an
      avoidance strategy, whereas hamsters increase muscle capillarity in part as a
      consequence of disuse atrophy.

PMID- 11571491
TI  - Effect of losartan on sodium appetite of hypothyroid rats subjected to water and
      sodium depletion and water, sodium and food deprivation.
AB  - The involvement of angiotensin AT1 receptors in sodium appetite was studied in
      hypothyroid rats treated with the angiotensin II antagonist losartan. Losartan
      was administered chronically by the oral route or acutely by the subcutaneous
      route after water and sodium depletion or water, sodium and food deprivation.
      Three days after addition of losartan to the food at the dose of 1.0 mg x g(-1),
      the rats significantly reduced (P < 0.02) their spontaneous intake of 1.8% NaCl.
      Increasing the dose of losartan to 2.0 and 4.0 mg x g(-1) did not reduce NaCl
      intake; in contrast, the intensity of the sodium appetite gradually returned to
      previous levels. The simultaneous administration of captopril, an angiotensin
      converting enzyme inhibitor, and losartan significantly increased (P < 0.05) NaCl
      intake and after captopril removal NaCl intake returned to the levels observed
      with losartan treatment alone. The administration of losartan 4 days after the
      beginning of captopril treatment significantly reduced (P < 0.0001) NaCl intake.
      Following acute administration of losartan, water- and sodium-depleted rats
      significantly reduced their NaCl and water intake (P < 0.001). The administration
      of losartan also induced a significant reduction in NaCl and water intake in
      water, NaCl and food-deprived rats (P < 0.0001 and P < 0.001, respectively). The
      present results show that chronic treatment with oral losartan inhibited
      spontaneous sodium appetite in hypothyroid rats. Continuation of treatment
      rendered rats resistant to the blockade of AT1 receptors. Water and sodium
      depletion and water, NaCl and food deprivation induced sodium appetite, which in
      the short term depends on cerebral angiotensinergic activity mediated by the
      activation of AT1 receptors.

PMID- 11571493
TI  - Effects of carbonic anhydrase inhibition on the responsiveness of laryngeal
      receptors in cats to CO2.
AB  - The effects of carbonic anhydrase inhibition on the responsiveness to CO2 of
      pressure-sensitive laryngeal receptors were examined in anaesthetised, paralysed
      cats. Laryngeal CO2-sensitive receptors from the superior laryngeal nerve were
      selected by their responsiveness to intralaryngeal pressure and to perfusion of
      solution equilibrated with 9% CO2. The carbonic anhydrase inhibitor,
      methazolamide, when given intralaryngeally at 10(-4) M, diminished or abolished
      the responses to the CO2-equilibrated solution in four of six pressure-sensitive
      receptors. Histochemical staining for carbonic anhydrase activity showed that the
      larynges perfused with methazolamide had diminished carbonic anhydrase activity,
      especially on the superficial layers of surface epithelium. Compared to untreated
      controls, when given intravenously (50 mg x kg(-1)) methazolamide diminished or
      abolished the responses to CO2 of five of the six fibres studied. Histochemical
      staining of these larynges showed no carbonic anhydrase reactivity at the sites
      of laryngeal receptors. These results suggest that the responses to CO2 of
      laryngeal pressure-sensitive receptors are dependent on the presence of carbonic
      anhydrase. Inhibition of laryngeal receptor carbonic anhydrase activity by
      methazolamide is more reliably achieved by systemic rather than by luminal
      administration.

PMID- 11571494
TI  - Right ventricular distension alters monophasic action potential duration during
      pulmonary arterial occlusion in anaesthetised lambs: evidence for arrhythmogenic
      right ventricular mechanoelectrical feedback.
AB  - Abnormal loading and distension of the right ventricle may induce arrhythmia
      through the process of mechanoelectrical feedback. Nonetheless, the
      electrophysiological effects of right ventricular distension are ill-defined and
      the mechanisms which underpin mechanoelectrical feedback in the right ventricle
      are unknown. We examined the effects of changes in right ventricular load
      (complete occlusion of both caval veins or the main pulmonary artery) in 14
      anaesthetised lambs, instrumented with right ventricular surface electrodes and
      strain gauges for recording monophasic action potential and segment length, and
      an integrated conductance and micromanometer-tipped catheter for measurement of
      right ventricular pressure and volume. Caval occlusion did not alter right
      ventricular segment length and monophasic action potential duration. By contrast,
      pulmonary arterial occlusion increased the segment length and decreased the
      monophasic action potential duration at 25, 50 and 70% repolarisation by 29 +/-
      6, 22 +/- 4 and 17 +/- 3 ms, respectively (all P < 0.01). Of the 42 pulmonary
      arterial occlusions, 38 were associated with early afterdepolarisations (EADs)
      which increased progressively in magnitude as the occlusion was maintained until,
      in 32, overt arrhythmia was observed. By contrast, none of the four occlusions in
      which EADs were not observed resulted in arrhythmia. As a result, the proportion
      of occlusions which resulted in arrhythmia were greater in those associated with
      EADs than in those which were not (P = 0.002). Right ventricular distension
      alters the pattern of repolarisation, precipitates early afterdepolarisations and
      results in a variety of ventricular arrhythmia, including ventricular
      tachycardia.

PMID- 11571495
TI  - Determinants of oxygen uptake kinetics in older humans following single-limb
      endurance exercise training.
AB  - We hypothesised that the observed acceleration in the kinetics of exercise on
      transient oxygen uptake (VO2) of five older humans (77 +/- 7 years (mean +/-
      S.D.) following 9 weeks of single-leg endurance exercise training was due to
      adaptations at the level of the muscle cell. Prior to, and following training,
      subjects performed constant-load single-limb knee extension exercise. Following
      training VO2 kinetics (phase 2, tau) were accelerated in the trained leg (week 0,
      92 +/- 44 s; week 9, 48 +/- 22 s) and unchanged in the untrained leg (week 0, 104
      +/- 43 s; week 9, 126 +/- 35 s). The kinetics of mean blood velocity in the
      femoral artery were faster than the kinetics of VO2, but were unchanged in both
      the trained (week 0, 19 +/- 10 s; week 9, 26 +/- 11 s) and untrained leg (week 0,
      20 +/- 18 s; week 9, 18 +/- 10 s). Maximal citrate synthase activity, measured
      from biopsies of the vastus lateralis muscle, increased (P < 0.05) in the trained
      leg (week 0, 6.7 +/- 2.0 micromol x (g wet wt)(-1) x min(-1); week 9, 11.4 +/-
      3.6 micromol x (g wet wt)(-1) x min(-1)) but was unchanged in the untrained leg
      (week 0, 5.9 +/- 0.5 micromol x (g wet wt)(-1) x min(-1); week 9, 7.9 +/- 1.9
      micromol x (g wet wt)(-1) x min(-1)). These data suggest that the acceleration of
      VO2 kinetics was due to an improved rate of O2 utilisation by the muscle, but was
      not a result of increased O2 delivery.

PMID- 11571496
TI  - A comparison of modelling techniques used to characterise oxygen uptake kinetics
      during the on-transient of exercise.
AB  - We compared estimates for the phase 2 time constant (tau) of oxygen uptake (VO2)
      during moderate- and heavy-intensity exercise, and the slow component of VO2
      during heavy-intensity exercise using previously published exponential models.
      Estimates for tau and the slow component were different (P < 0.05) among models.
      For moderate-intensity exercise, a two-component exponential model, or a mono
      exponential model fitted from 20 s to 3 min were best. For heavy-intensity
      exercise, a three-component model fitted throughout the entire 6 min bout of
      exercise, or a two-component model fitted from 20 s were best. When the time
      delays for the two- and three-component models were equal the best statistical
      fit was obtained; however, this model produced an inappropriately low
      DeltaVO2/DeltaWR (WR, work rate) for the projected phase 2 steady state, and the
      estimate of phase 2 tau was shortened compared with other models. The slow
      component was quantified as the difference between VO2 at end-exercise (6 min)
      and at 3 min (DeltaVO2 (6-3 min)); 259 ml x min(-1)), and also using the phase 3
      amplitude terms (truncated to end-exercise) from exponential fits (409-833 ml x
      min(-1)). Onset of the slow component was identified by the phase 3 time delay
      parameter as being of delayed onset approximately 2 min (vs. arbitrary 3 min).
      Using this delay DeltaVO2 (6-2 min) was approximately 400 ml x min(-1). Use of
      valid consistent methods to estimate tau and the slow component in exercise are
      needed to advance physiological understanding.

PMID- 11571497
TI  - Carotid baroreceptor reflexes in humans during orthostatic stress.
AB  - Orthostatic stress, including standing, head-up tilting and lower body suction,
      results in increases in peripheral vascular resistance but little or no change in
      mean arterial pressure. This study was undertaken to determine whether the
      sensitivity of the carotid baroreceptor reflex was enhanced during conditions of
      decreased venous return. We studied eight healthy subjects and determined
      responses of pulse interval (ECG) and forearm vascular resistance (mean finger
      blood pressure divided by Doppler estimate of brachial artery blood velocity) to
      graded increases and decreases in carotid transmural pressure, effected by a neck
      suction/pressure device. Responses were determined with and without the
      application of lower body negative pressure (LBNP) at -40 mmHg. Stimulus-response
      curves were determined as the responses to graded neck pressure changes and the
      differential of this provided estimates of reflex sensitivity. Changes in carotid
      transmural pressure caused graded changes in R-R interval and vascular
      resistance. The cardiac responses were unaffected by LBNP. Vascular resistance
      responses, however, were significantly enhanced during LBNP and the peak gain of
      the reflex was increased from 1.2 +/- 0.3 (mean +/- S.E.M.) to 2.2 +/- 0.3 units
      (P < 0.05). The increased baroreflex gain may contribute to maintenance of blood
      pressure during orthostatic stress and limit the pressure decreases during
      prolonged periods of such stress.

PMID- 11571498
TI  - Impaired phospholipid-related signal transduction in advanced Huntington's
      disease.
AB  - The aim of this study was to test the hypothesis that Huntington's disease is
      associated with impaired phospholipid-related signal transduction using the
      niacin skin flush test. This is the first reported use of this test in this
      patient group. The response to topical aqueous methyl nicotinate solution was
      recorded at 5 min intervals over 20 min in six in-patients with advanced (stage
      III) Huntington's disease and in 14 age- and sex-matched normal individuals with
      no history of this or any other major neurological disorder. The volumetric
      niacin response (VNR) (mean +/- S.E.M.) in the patients with Huntington's
      disease, 16.3 +/- 2.6 mol x s x l(-1), was significantly lower than the mean VNR
      of 28.3 +/- 2.1 mol x s x l(-1) in the control group (P = 0.004). These results
      are consistent with the conclusion that Huntington's disease may be associated
      with an abnormality of neuronal membrane fatty acid metabolism, possibly as a
      consequence of an as yet unidentified action of huntingtin.

PMID- 11571501
TI  - Hematopoietic stem cell transplantation between red cell incompatible donor
      recipient pairs.
AB  - Transplantation between red cell-disparate donor and recipient is feasible with
      minimal increase in the risk of transplantation if consideration is given to the
      immunohematological consequences of the transplant. The risks of immediate and
      delayed hemolysis must be managed. Some recipients will experience a delay in the
      recovery of red blood cells.

PMID- 11571502
TI  - Prevention of accelerated presbycusis by bone marrow transplantation in
      senescence-accelerated mice.
AB  - A substrain of the senescence-accelerated mouse (SAM), the SAMP1 mouse, is an
      animal model for accelerated senescence including the age-related acceleration of
      both immunological dysfunction and hearing loss caused by the impairment of
      spiral ganglion cells. In the present study, we examine whether the accelerated
      presbycusis can be prevented by allogeneic BMT. Young SAMP1 (H-2(k)) mice were
      irradiated with 9 Gy and then reconstituted with bone marrow cells from normal
      BALB/c (H-2(d)) mice. Allogeneic BMT was found to prevent the development of
      immunological dysfunction, hearing loss, and apoptosis of spinal ganglion cells
      in SAMP1 mice. These findings indicate that some types of accelerated presbycusis
      do not result from defects in the cochlea, but do from defects in the
      hematopoietic stem cells (HSC) and immunocompetent cells derived from the HSC. If
      this is the case, either allogeneic BMT, which replaces abnormal HSC with normal
      HSC and reconstructs a normal immune system in the recipients, or autologous BMT
      using genetically modified bone marrow cells, could become a new strategy for the
      treatment of presbycusis.

PMID- 11571503
TI  - Synergistic effects of pegylated recombinant human megakaryocyte growth and
      development factor and granulocyte colony-stimulating factor on mobilization of
      hematopoietic progenitor and stem cells with long-term repopulating ability into
      peripheral blood in mice.
AB  - We investigated the effects of pegylated recombinant human megakaryocyte growth
      and development factor (PEG-rHuMGDF) on peripheral blood progenitor cell (PBPC)
      mobilization and the combined effect of PEG-rHuMGDF plus recombinant human
      granulocyte colony-stimulating factor (rhG-CSF) in C57BL/6 mice. Treatment of
      mice with PEG-rHuMGDF increased the numbers of day 8 and day 12 spleen colony
      forming units (CFU-S), and pre-CFU-S in the PB. Ten days administration of PEG
      rHuMGDF could mobilize higher numbers of days 8 and day 12 CFU-S than 5 days
      administration. An optimal dose of PEG-rHuMGDF mobilized a higher number of
      committed progenitor cells (day 8 CFU-S) and a lower number of immature
      progenitor cells (pre-CFU-S) into PB than rhG-CSF. The combined administration of
      optimal or suboptimal doses of PEG-rHuMGDF and rhG-CSF induced synergistic
      effects on mobilization of CFU-S and pre-CFU-S into PB compared to either factor
      alone. Four months after sex-mismatched PBPC transplantation, long-term donor
      derived engraftment was observed in all recipients that had been transplanted
      with PBPCs mobilized by rhG-CSF and/or PEG-rHuMGDF, as determined by Y-chromosome
      polymerase chain reaction (PCR) analysis. Our data suggest that cytokine-induced
      pathways for PBPC mobilization may be different between PEG-rHuMGDF and rhG-CSF
      and indicate that PEG-rHuMGDF alone or the combination with rhG-CSF may be useful
      in effective PBPC mobilization.

PMID- 11571504
TI  - Reduced intensity conditioning: enhanced graft-versus-tumor effect following dose
      reduced conditioning and allogeneic transplantation for refractory lymphoid
      malignancies after high-dose therapy.
AB  - Non-myeloablative regimens have been proven to allow engraftment following
      allogeneic stem cells transplantation (allo-SCT) with minimal procedure-related
      toxicity. Conventional allo-SCT may produce remissions in patients with relapsed
      and refractory lymphoid malignancies (LM) but these good results may be achieved
      at the cost of high treatment-related morbidity and mortality. Application of
      allo-SCT using less intensive regimens may temper the frequency of these
      complications, allowing a potent graft-versus-tumor effect (GVT). We present our
      data on 11 patients with LM receiving allo-SCT with a reduced regimen. Ten
      patients had received previous high-dose therapy, and were at high risk for
      toxicity, thus precluding the use of allo-SCT. A fludarabine and low-dose
      busulfan combination facilitated engraftment while exerting GVT. Hematological
      recovery was quick, and full donor T cell chimerism preceded acute GVHD. GVHD and
      infections were the major problems. Spontaneous acute GVHD occurred in eight
      patients (72%). Five patients (45%) achieved complete remission, and the GVT
      effect was closely associated with GVHD. These results support the concept that
      GVT is effective against LM in patients who have been heavily pretreated. Further
      studies are needed to investigate strategies to generate more specific
      alloreactive effects providing optimal GVT and an acceptable risk of GVHD and
      infections.

PMID- 11571505
TI  - Reduced-intensity conditioning reduces the risk of severe infections after
      allogeneic peripheral blood stem cell transplantation.
AB  - We compared the occurrence of severe infections following 71 reduced-intensity
      conditioning (RIC) allogeneic peripheral blood stem cell transplants (PBSCT) and
      123 standard myeloablative PBSCT (MINI and STAND groups, respectively) from HLA
      identical siblings. The probability of 1-year infection-related mortality (IRM)
      was 19% in the STAND group and 10% in the MINI group (log-rank, P = 0.3). On
      multivariate analysis the only significant variable associated with a higher risk
      of IRM was the development of moderate-to-severe GVHD (P = 0.005). The
      probability of developing CMV infection was 39% in the STAND group and 21% in the
      MINI group (P = 0.03) (43% and 21%, respectively, in seropositive donor/recipient
      pairs, P = 0.01), and the probability of developing CMV disease was 9.5% and 1%,
      respectively (P = 0.05) (11% and 1%, respectively, in seropositive
      donor/recipient pairs, P = 0.03). Multivariate analysis of CMV infection
      identified four variables associated with a higher risk: CMV positive serostatus
      (P = 0.05), STAND transplant group (P = 0.02), the development of moderate-to
      severe GVHD (P < 0.001) and a dose of CD34(+) cells infused below 6 x 10(6)/kg (P
      = 0.01). Invasive fungal infections and pneumonias of unknown origin did not
      differ between groups, and neither did other severe non-CMV viral infections and
      bacterial infections. Our results suggest that RIC allogeneic PBSCT may decrease
      the risk of dying from an opportunistic infection and reduces the occurrence of
      CMV infection and disease. Overall, the development of GVHD (acute or chronic) is
      an important risk factor for these complications. Other infections continue to
      pose a significant threat to recipients of RIC allografts, stressing that
      prophylactic and supportive measures are an important aspect in their care.

PMID- 11571506
TI  - Allogeneic transplantation of CD34+-selected cells from peripheral blood in
      patients with myeloid malignancies in early phase: a case control comparison with
      unmodified peripheral blood transplantation.
AB  - An allogeneic transplantation of CD34(+)-selected cells from peripheral blood
      (allo-PBT/CD34(+)) from HLA-identical sibling donors was performed in 50 adult
      patients with acute myeloid leukemia in first complete remission (AML CR1) (n =
      29), myelodysplastic syndrome (MDS) (n = 4), or chronic myeloid leukemia in first
      chronic phase (CML CP1) (n = 17). Clinical results were compared to a concurrent
      group of 50 patients transplanted with unmodified peripheral blood progenitor
      cells (allo-PBT), matched for age, diagnosis, and disease stage. The median
      follow-up period was 29 months (range 1-69). The actuarial probability of
      developing acute GVHD clinical grade II to IV was 16% (95%CI: 6-26) for the allo
      PBT/CD34(+) group and 41% (95%CI: 29-57) for the allo-PBT group (P = 0.002). The
      actuarial probability of developing extensive chronic GVHD was 22% (95%CI: 8-36)
      for the allo-PBT/CD34(+) group and 47% (95%CI: 31-63) for the allo-PBT group (P =
      0.02). Recipients of allo-PBT/CD34(+) had less toxicity associated with the
      transplant and better Karnofsky index at the last follow-up. For AML/MDS
      patients, the actuarial probability of disease-free survival (DFS) for recipients
      of allo-PBT/CD34(+) and allo-PBT was 65% (95%CI: 45-85) vs43% (95%CI: 28-58) (P =
      0.05), respectively. These data provide a rationale for a randomised trial of
      allo-PBT/CD34(+) vs allo-PBT in AML/MDS patients in early stage of the disease.

PMID- 11571508
TI  - Obesity and autologous stem cell transplantation in acute myeloid leukemia.
AB  - In the bone marrow transplant setting, several authors hypothesized that severely
      overweight patients are at increased risk of transplant-related toxicity, but
      different definitions of obesity, different body weight groupings and
      heterogeneous samples of patients were analyzed. To overcome these limitations,
      we retrospectively considered a homogeneous group of 54 patients (median age 36.5
      years), with a diagnosis of de novo acute myeloid leukemia (AML), autografted in
      first complete remission (CR) with the Bu-Cy2 conditioning regimen, dosed on
      actual body weight. Patients were classified into three groups (obese, non-obese,
      underweight) using body mass index (BMI = kg/m(2)); for each group we analyzed
      transplant-related toxicity and mortality, overall survival and disease-free
      survival (OS/DFS). In spite of the relatively small number of patients, in our
      results high BMI appears a predictive factor for an increase of treatment-related
      toxicity and mortality. Moreover, 30 (55%) patients are currently alive in
      continuous CR, and after a median follow-up of 76.5 months (range 14-137)
      statistically significant differences in OS and DFS were detected between obese
      and non-obese groups (P = 0.012 and 0.021, respectively). Our study suggests that
      obesity may represent an independent risk factor for autograft in AML and further
      investigations are warranted.

PMID- 11571507
TI  - Cord blood transplants: early recovery of neutrophils from co-transplanted
      sibling haploidentical progenitor cells and lack of engraftment of cultured cord
      blood cells, as ascertained by analysis of DNA polymorphisms.
AB  - The number of infused cells is a very important factor in cord blood transplant
      (CBT) engraftment. Prior ex vivo expansion of aliquots of transplanted cord blood
      (CB) units is being investigated as a procedure to increase engraftment
      potential, but results are difficult to evaluate due to a lack of markers for
      assessing the contribution of expanded cells. We transplanted five patients,
      infusing the best available CB unit and cells from a second donor simultaneously.
      In two patients, these cells were obtained from another frozen CB unit by
      CD34(+)positive selection and culture expansion; the other three patients
      received uncultured highly purified haploidentical CD34(+) cells. The first two
      patients had DNA from the culture expanded CB cells detected only for a few days
      around day +11 when the absolute neutrophil count (ANC) was >200/microl;
      thereafter and when the ANC was <500/microl, only donor DNA from the uncultured
      CB was detected. For the other three patients, DNA analysis showed early and
      transient granulocyte engraftment of haploidentical cells, progressively replaced
      by the CB-derived granulocytes. We concluded that: (1) simultaneous infusion of
      lymphocyte-depleted HLA highly mismatched haematopoietic progenitor cells has not
      produced unfavourable effects for CBT; (2) the double transplant model is
      suitable for evaluating the engraftment potential of ex vivocultured CB cells in
      the clinical setting; (3) the culture conditions used did not result in early
      recovery of ANC; and (4) co-transplantation of purified uncultured HLA
      haploidentical CD34(+) cells may reduce the time of neutropenia following CBT.

PMID- 11571509
TI  - Unrelated allogeneic bone marrow donation: short- and long-term follow-up of 103
      consecutive volunteer donors.
AB  - Between 1992 and 1999, 105 unrelated allogeneic bone marrow collections from 103
      volunteer donors (65 males and 38 females; median age 33 years) were carried out
      in three northern Italian centers (Verona, Bolzano and Padova) affiliated with
      the Italian Bone Marrow Donor Registry (IBMDR). The average volume of BM
      collected was equivalent in both genders (1143.1 ml for males and 1054.2 ml for
      females; P = 0.1), although the average volume collected for unit of body weight
      and the average post-collection blood volume depletion was higher in females
      (respectively 17.1 ml/kg and 14.2% in females, 14.8 ml/kg and 12% in males; P=
      0.01 and 0.03). There was no statistically significant difference between males
      and females in the total number of nucleated cells collected. We did not record
      any acute life-threatening event during or after the bone marrow collections. The
      most frequent complaint was pain at the collection site (77%) followed by the
      onset of fatigue (38%) and nausea and vomiting (25%); all of these were short
      term problems. Hospitalization was short (average 20.2 h) and donors started
      their normal daily activities after an average of 5.4 days. We also monitored Hb,
      serum ferritin levels, WBC and platelet counts in the post-collection period
      (average follow-up 40.1 months). All donors signed a written informed consent for
      a further bone marrow collection, if needed. Our findings confirm the short- and
      long-term safety of allogeneic bone marrow collection in volunteer donors.

PMID- 11571510
TI  - Superior survival of blood and marrow stem cell recipients given maternal grafts
      over recipients given paternal grafts.
AB  - During the reproductive period, mothers and offspring exchange hematopoietic
      cells and develop a form of immunological tolerance bidirectionally. To examine
      whether previous experience of such communication has any remote effect when
      maternal hematopoietic cells are later transplanted to the children, we
      retrospectively compared the outcomes of blood and marrow stem cell
      transplantation from maternal donors (n = 46) to those from paternal donors (n =
      50) by using the database of the Japanese nationwide surveys for adult
      hematopoietic cell transplants between 1990 and 1998. At 5 years, recipients of
      maternal hematopoietic cells had a significantly higher overall survival than
      patients receiving paternal grafts (60% vs 32%, P = 0.006). Although no
      significant difference was observed in the occurrence of severe acute GVHD (grade
      > or =III) and the relapse of malignant diseases between two groups, the
      probability of non-relapse treatment-related mortality was significantly lower
      after maternal donor transplants. Furthermore, multivariate analysis revealed
      that parental donor type was the only factor significantly associated with
      overall survival. In conclusion, our analysis indicates superior survival of
      maternally donated recipients in hematopoietic stem-cell transplantations from
      biological parents. This finding has important implications in the selection of
      alternative familial donors, and warrants further prospective analysis of
      parental donor transplantations.

PMID- 11571511
TI  - High incidence of gastrointestinal tract bleeding after autologous stem cell
      transplant for primary systemic amyloidosis.
AB  - Peripheral blood stem cell transplants have been associated with better response
      rates than conventional chemotherapy in patients with primary systemic
      amyloidosis. A higher incidence of gastrointestinal (GI) tract bleeding has been
      observed among amyloidosis patients undergoing peripheral stem cell
      transplantation. We retrospectively reviewed the medical records of such patients
      to identify those who had GI tract bleeding in the post-transplant period. Forty
      five patients were studied. Nine patients had GI tract bleeding in the post
      transplant period. The median post-transplant duration to onset of bleeding was
      9.5 days (range 1 to 48 days). Three patients had lower GI tract bleeding, two
      had upper GI tract bleeding, and four had both. Diffuse esophagitis and gastritis
      were the most common findings on endoscopy. There were no correlations among the
      age, platelet nadir, or CD34 count of the graft and the risk of bleeding. Women
      were more likely to have GI tract bleeding (P = 0.015), as were patients with
      slow platelet engraftment (P = 0.02). Patients with multiorgan involvement and
      those on hemodialysis appeared to be at a higher risk of GI tract bleeding. The
      mean post-transplant hospital stay for those with GI tract bleeding was 37 days
      compared with 14.5 days for those who did not have GI tract bleeding (P =
      0.0047).

PMID- 11571512
TI  - Decreased bone mineral density is common after autologous blood or marrow
      transplantation.
AB  - Survivors of autologous blood or marrow transplantation (ABMT) are predisposed to
      decreased bone mineral density (BMD), but data are lacking on the incidence and
      risk factors for this condition. Therefore, we measured BMD in 64 of 68
      consecutive ABMT survivors (35 men and 29 women) attending the University of
      Toronto ABMT long-term follow-up clinic. Patients were evaluated a median of 4.2
      years (range: 4.9 months-11.4 years) after ABMT. Median age at evaluation was
      49.6 years (range: 23.5-68.2 years). At the L1-L4 vertebrae, 17 (26%) patients
      (eight men and nine women) had osteopenia and one male (2%) had osteoporosis.
      Mean BMD at L1-L4 did not differ from healthy young adults or age and sex matched
      controls. At the femoral neck, 30 patients (46%) (18 men and 12 women) had
      osteopenia and five (8%) (two men and three women) had osteoporosis. Mean BMD at
      the femoral neck was significantly lower than in healthy young adults and age-
      and sex-matched controls. By regression analysis, patients with decreased BMD
      were older than those with normal BMD (P = 0.02). Gender, body mass index, time
      from BMT to evaluation and presence of hypogonadism were not associated with
      decreased BMD. Treatment of decreased bone density was instituted and follow-up
      data were obtained 1 year after treatment in 22 of 39 patients with reduced BMD.
      Nineteen (86%) patients had stabilization or improvement of their bone density at
      follow-up. We conclude that, after ABMT, over half of the patients have evidence
      of osteopenia or osteoporosis. Men and women were equally affected. In our study,
      only older age at evaluation was predictive for loss of BMD. We recommend the
      measurement of BMD as an integral component to the follow-up of ABMT patients.

PMID- 11571513
TI  - Abnormal cervical cytology in bone marrow transplant recipients.
AB  - Particular human papillomavirus (HPV) subtypes are implicated in the genesis of
      abnormal cervical cytology and cervical cancer. While most immunocompetent hosts
      clear HPV infection with no sequelae, some develop premalignant cytological
      changes of whom a minority subsequently progress to overt carcinoma.
      Immunocompromised patients, such as renal allograft recipients and HIV-infected
      individuals, have a higher rate of cytological abnormalities. This is thought to
      be due to prolonged persistence of virus due to impaired clearance by the immune
      system. We undertook a retrospective review of the cervical cytology of all women
      who underwent BMT at two transplant centres and who had cervical smears performed
      between 1990 and 1998. The rate of cytological abnormalities was significantly
      higher than in the general population before BMT (age-adjusted odds ratio (OR)
      2.2, P = 0.02) and after BMT (OR 7.0, P < 0.0001). After BMT, allogeneic
      recipients had a higher rate of abnormalities than did autologous patients (OR
      2.6, P = 0.02) although only allogeneic recipients had a higher rate of
      abnormalities post-BMT compared to pre-BMT (allogeneic OR 6.8, P = 0.004). These
      observations suggest that pre-transplant disease and treatment factors increase
      the risk of cytologic abnormalities and that transplant-related factors such as
      conditioning therapy and immunosuppression further increase this risk. These data
      suggest that more frequent screening may be required in these at-risk groups,
      especially allogeneic recipients. Prospective studies are required to further
      evaluate cytological abnormalities and HPV shedding in these populations.

PMID- 11571514
TI  - Pulmonary toxicity syndrome following CDEP (cyclophosphamide, dexamethasone,
      etoposide, cisplatin) chemotherapy.
AB  - We report on three patients with multiple myeloma who developed drug-induced
      pneumonitis 1-2(1/2) months following maintenance (post autologous
      transplantation) chemotherapy with CDEP (cyclophosphamide, dexamethasone,
      etoposide, cisplatin) and 6-20 months after exposure to carmustine (BCNU) 300
      mg/m(2), used in combination with melphalan 140 mg/m(2), as pre-transplant
      conditioning regimen. All patients had either a proven (two) or suspected (one)
      fungal pneumonia and were treated with liposomal amphotericin B. Dyspnea, fever
      and cough were the prominent clinical symptoms, while air-space disease with
      ground glass appearance was seen radiographically. Histologic features typical
      for drug-induced lung injury were detected. All patients had a dramatic, clinical
      and radiographic response to a brief course of corticosteroids. Although CDEP
      induced pneumonitis appears to be a rare complication, its early recognition and
      prompt treatment, as well as its possible association with preceding fungal
      infection may have important clinical implications.

PMID- 11571515
TI  - Off-label use of recombinant factor VIIa in patients following bone marrow
      transplantation.
AB  - Recombinant factor VIIa (rFVIIa, NovoSeven) is FDA-approved for the treatment of
      bleeding in patients with hemophilia A/B with inhibitors. A growing literature
      suggests that there may be expanded indications for the use of NovoSeven in
      patients with significant bleeding who do not have a known factor deficiency.
      Severe bleeding refractory to standard hematologic or hemostatic support is
      common in patients undergoing bone marrow transplantation (BMT). We review our
      experience with rFVIIa in three patients (8 years 8 months to 19 years, median 13
      years) treated for pulmonary hemorrhage (n = 1), hemorrhagic cystitis (n = 3),
      and gastrointestinal bleeding (n = 2). Boluses of 90-270 microg/kg rVIIa with
      subsequent doses of 90 microg/kg every 4-24 h for 3-14 days were given,
      concurrent with maintaining platelet counts >50,000/mm(3). Transient clinical
      responses in gross hematuria (two patients) and in pulmonary hemorrhage were
      noted within several days of starting rFVIIa, but bleeding in a new site in two
      patients and renewed bleeding of the initial site in the third resulted in
      discontinuation of the drug. No toxicity or adverse events were observed while
      the patients were on rFVIIa treatment. Because of the substantial cost of this
      product, the lack of adequate monitoring methodology, and the variability of
      current dose and dosing intervals, large randomized studies are needed before
      definitive off-label use in the setting of BMT can be recommended.

PMID- 11571516
TI  - Griscelli syndrome: report of the first peripheral blood stem cell transplant and
      the role of mutations in the RAB27A gene as an indication for BMT.
AB  - Griscelli syndrome is characterized by partial albinism with variable
      immunodeficiency. Two different gene loci are responsible for this rare,
      autosomal recessive disease: the myosin Va gene and the RAB27A gene. As recently
      reported, only patients with mutations of the RAB27A gene suffer from
      immunodeficiency and hemophagocytic lymphohistiocytosis. Thus, only patients who
      suffer from the Griscelli syndrome with mutations of the RAB27A gene should
      receive BMT/PBSCT, which is the only curative therapy. Due to the risk of early
      relapse or severe infections, BMT/PBSCT should be carried out as soon as
      possible; if patients do not have HLA-identical family members, valuable time may
      be lost by searching for an HLA-identical unrelated donor. We report the first
      peripheral blood stem cell transplant (PBSCT) with T cell depletion in a 6-month
      old girl with Griscelli syndrome, and a deletion of the RAB27A gene. The donor
      was her phenotypically HLA-identical mother. Conditioning included busulfan, VP16
      and cyclophosphamide. The patient was transfused with 15.4 x 10(6)CD34-positive
      cells/kg and 17.6 x 10(3) CD3-positive cells/kg recipient weight. Three months
      after the transplant, a curable lymphoproliferative syndrome occurred. 26 months
      after the transplant, the patient is doing well with stable mixed chimerism (52%
      donor cells).

PMID- 11571517
TI  - Successful unrelated BMT in a patient with Kostmann syndrome complicated by pre
      transplant pulmonary 'bacterial' abscesses.
AB  - Kostmann syndrome, severe congenital neutropenia, is often associated with life
      threatening bacterial infections. A 5-year-old girl with Kostmann syndrome
      developed pulmonary abscesses. She was refractory to granulocyte colony
      stimulating factor and antibiotics. She underwent unrelated HLA-matched BMT.
      Myeloablative conditioning consisted of 12-Gy TBI with lung shielding,
      antithymocyte globulin, etoposide, and cyclophosphamide. After successful
      engraftment, the pulmonary abscesses resolved by day 75 post-transplant. Although
      the option of transplantation is not established in the setting of unrelated HLA
      matched BMT in Kostmann syndrome, this case may provide useful information.
      Furthermore, pre-transplant pulmonary bacterial abscesses may not be a
      contraindication for BMT in some patients with Kostmann syndrome.

PMID- 11571518
TI  - Late onset post-transplantation lymphoproliferative disease of recipient origin
      following cytogenetic relapse and occult autologous haematopoietic regeneration
      after allogeneic bone marrow transplantation for acute myeloid leukaemia.
AB  - A post-transplantation lymphoproliferative disease (PTLD) of recipient origin was
      identified in one of 376 consecutive cases of allogeneic bone marrow
      transplantation (BMT). This occurred in a 36-year-old woman who received an
      allogeneic BMT for acute myeloid leukaemia in relapse. At 15 months after BMT,
      recipient haematopietic and leukaemic cells were found in the bone marrow, which
      disappeared on withdrawal of immunosuppression. However, severe graft-versus-host
      disease (GVHD) necessitated the continuation of immunosuppression, leading to the
      occurrence of PTLD in the liver and lung 12 months afterwards. Fluorescence in
      situ hybridisation showed that the neoplastic cells were of recipient origin.
      Although the PTLD also responded completely to withdrawal of immunosuppression,
      the patient finally died from the complications of GVHD. This case of late onset
      PTLD post-BMT showed features similar to those in solid organ transplantation, in
      that the tumour was of recipient origin and responded well to the withdrawal of
      immunosuppression. Of further interest is that recipient lymphoid regeneration
      had accompanied autologous haematopoietic regeneration and become a target for
      subsequent neoplastic transformation.

PMID- 11571519
TI  - Intravenous cyclosporine and tacrolimus caused anaphylaxis but oral cyclosporine
      capsules were tolerated in an allogeneic bone marrow transplant recipient.
AB  - A Japanese female patient with angioimmunoblastic T cell lymphoma underwent
      allogeneic bone marrow transplantation (BMT) from her brother. Cyclosporine at a
      dose of 3 mg/kg was started by continuous infusion over 24 h on day -1 of BMT.
      Within a couple of minutes after the infusion was begun, she developed diffuse
      pruritic erythema on her whole body and tachycardia. The infusion was immediately
      stopped and corticosteroid was given, resulting in disappearance of the erythema
      gradually. She was then switched to intravenous tacrolimus. However, she suffered
      urticalial erythema again. Since polyoxyethylated castor oil, a solubilizer used
      in the injective formulation of both cyclosporine and tacrolimus, is considered
      to be responsible for the reaction, she was given oral capsules of cyclosporine
      (Sandimmun) in which polyoxyethylated castor oil was not contained. No further
      anaphylactic reaction was observed. The BM cells were successfully engrafted
      without causing severe GVHD. She was discharged on cyclosporine capsules without
      any further adverse effects. Anaphylaxis to intravenous cyclosporine and
      tacrolimus is a very rare but a serious complication. Our present case indicates
      that oral capsule of Sandimmun is a safe alternative to prevent GVHD in such a
      case of anaphylactic reaction against intravenous formulation.

PMID- 11571522
TI  - Standards of stem cell transplantation: Part I: the accreditation of paediatric
      stem cell transplantation centres within the EBMT; Part II: intensive care units
      in paediatric stem cell transplantation; Part III: informed consent and sibling
      donor issues.

PMID- 11571523
TI  - Follow up and late effects.

PMID- 11571524
TI  - The management of relapsed acute lymphoblastic leukaemia.

PMID- 11571525
TI  - Bone marrow transplantation in thalassemia.

PMID- 11571526
TI  - The cure of the thalassemia with bone marrow transplantation.

PMID- 11571527
TI  - Immune recovery and immunotherapy after stem cell transplantation in children.
AB  - Careful longitudinal studies of the lymphoid cell recovery after stem cell
      transplantation with other than HLA-identical sibling donors illustrated the
      prolonged T- and B-cellular immunodeficiency post-SCT, whereas NK-cell recovery
      was fast. Only low numbers of CD45RO memory T-cells, with a restricted TCR
      repertoire, are present in the first 6 months post-SCT. The consequence is an
      increased risk of viral infections and possibly of leukemia relapse. The latter
      complication can be prevented by enhancing the anti-leukemic immune reactivity
      shortly after SCT. Different technical approaches were presented, the majority of
      them still being in the pre-clinical phase. NK-cell reactivity based on KIR
      epitope mismatches between donor and recipient are promising for AML- and CML-,
      not for ALL-patients. The ALL-blasts may be killed by an antibody-dependent
      cellular cytotoxicity, using anti-CD19 antibodies, as was shown to be effective
      in vitro. Also the generation of leukemia-specific CTL's, making use of
      differences in minor histocompatibility antigens between donor and recipient, is
      now operational and may be a highly effective approach in a number of leukemic
      graft recipients.

PMID- 11571528
TI  - New forms of transplantation: haploidentical transplants.

PMID- 11571529
TI  - Infections after stem cell transplantation in children: state of the art and
      recommendations.
AB  - At the workshop on infections after stem cell transplantation (SCT) in children,
      the following topics were introduced by invited speakers and discussed with the
      audience: empirical antimicrobial therapy in the pre-engraftment period, early
      diagnosis of fungal and viral infections and possibilities to treat them and the
      possible role of G-CSF early post-SCT. Episodes of fever in the pre-engraftment
      period mostly are unexplained, and in about one quarter due to bacteremia, mostly
      by Gram-positive cocci. No single drug or combination of drugs used for
      antimicrobial therapy is superior, neither does it cover 100% of the pathogens.
      Close microbiological surveillance of the patients and knowledge of the local
      microbial epidemiology are requested for optimal therapy. Early fungal infections
      are reactivations of pre-SCT infections, late fungal infections mostly are
      associated with failure of engraftment or GvHD and its treatment. Except for
      suggestive ultrasound or CT-scan abnormalities, the possibilities for early
      diagnosis are limited c.q. not reliable. Fluconazol prophylaxis is recommended to
      prevent Candida albicans invasion. A number of new antifungal drugs are being
      tested in phase I and II studies. CMV, EBV and adenoviruses may reactivate after
      SCT, causing severe disease with a high mortality, especially in non-HLA
      identical donor-recipient combinations. Frequent surveillance cultures for CMV
      and adenoviruses, pp65-CMV antigen detection in WBC and PCR techniques for CMV,
      EBV and adenoviruses all have their own contribution to the early diagnosis of
      dissemination of the viral infection. Therapeutical possibilities, except with
      respect to ganciclovir and foscarnet for CMV infection, are still limited. The
      effectiveness of cidofovir is under study. Adoptive therapy with virus-specific
      CTL's probably represents the new frontier. G-CSF administration early after SCT
      has a beneficial effect on PMN recovery, hospitalization time, use of antibiotics
      and total parenteral nutrition requirement in children undergoing allogeneic and
      autologous BMT. No benefit is observed in children undergoing peripheral blood
      SCT. The routine use of G-CSF in the latter group of patients is not justified.

PMID- 11571530
TI  - Prospective study on allogeneic bone marrow transplantation (allo BMT) versus
      chemotherapy (chemo) for very high-risk (VHR) childhood acute lymphoblastic
      leukaemia in first complete remission.

PMID- 11571531
TI  - Psychosocial care in children with stem cell transplantation.
AB  - The paper describes adaptation processes of children undergoing stem cell
      transplantation. Results from a prospective longitudinal study indicate two
      different levels of emotional adaptation. The children's good adaptation to the
      facts of treatment are a result of heavy inner work. The child's neuroticism and
      anxiety scores and the parents' coping style and experienced social support seem
      to have an influence on the occurrence of severe adjustment disorders during SCT.
      It is important to recognise the child's inner processes and the family's
      influences before and during SCT.

PMID- 11571532
TI  - Significant augmentation of pro-apoptotic gene therapy by pharmacologic bcl-xl
      down-regulation in mesothelioma.
AB  - The ratio of pro-apoptotic (PAP) and anti-apoptotic (AAP) bcl-2 proteins is
      important in apoptosis regulation. We sought to determine if inhibition of the
      AAP bcl-xl by sodium butyrate (SB) would augment apoptotic cellular death in
      mesothelioma when combined with adenoviral pro-apoptotic gene therapy (PAGT) by
      simultaneously increasing PAP and decreasing AAP in these cells. Human
      mesothelioma cell lines were exposed to AdBax, AdBak, Adp53, and SB alone as well
      as all vectors combined with SB at varying doses and time points. Cell death was
      assessed, and apoptosis evaluated by morphology and FACS. Isobologram analysis
      evaluated additive or synergistic effect. Cellular death and apoptosis were
      augmented by PAGT/SB combinations compared to monotherapy. Following AdBax/SB and
      AdBak/SB, a decrease of the AAP bcl-xl was noted in combination with increases in
      PAP bax and bak. By isobologram analysis, additive or synergistic cell killing
      was noted with both combinations. SB treatment did not significantly augment cell
      killing or apoptosis in combination with Adp53. PAGT/SB was more effective than
      monotherapy in induction of apoptotic cell death. Synergy may be due to the
      ability of SB to decrease bcl-xl with marked increases in PAP engendered by PAGT.
      Combination therapy with agents that down-regulate AAP in addition to PAGT may
      prove useful clinically.

PMID- 11571533
TI  - Single-chain antibody-mediated gene delivery into ErbB2-positive human breast
      cancer cells.
AB  - Targeted gene transfer by nonviral vectors can be achieved through incorporation
      of specific ligand(s) into the vectors. In this study, the effects of
      incorporation of an anti-ErbB2 single-chain antibody fragment (ScFv) into
      nonviral vectors for targeted gene delivery were investigated. The ML39 ScFv,
      selected from a human ScFv phage display library and affinity matured in vitro
      (K(d)=1 x 10(-9) M), was used as ligand specific for the extracellular domain of
      the tumor surface protein, ErbB2. Two approaches were taken: (a) development of a
      vector that is composed of a bifunctional fusion protein capable of binding DNA
      with the ErbB2-specific ML39 ScFv at its N-terminus and a truncated form of human
      protamine at its C-terminus, and (b) formulation and evaluation of delivery
      vectors consisting of three independent components including ML39 ScFv,
      protamine, and cationic lipids. We demonstrate that fusion proteins comprised of
      the ML39 ScFv and a truncated form of protamine, denoted as ScFv-P-S, can
      selectively deliver exogenous DNA into ErbB2(+) cells, with an 8- to 10-fold
      increase in expression levels of the luciferase reporter gene in ErbB2(+) cells
      as compared to ErbB2(-) cells. In addition, vectors formulated by appropriately
      mixing DNA, ScFv, protamine, and lipids in vitro could even more efficiently
      deliver the reporter gene into ErbB2(+) cells with approximately 5-fold increase
      in gene expression in ErbB2(+) cell as compared to ErbB2(-) cells. Expression and
      refolding of the ScFv fusion proteins, in addition to determination of optimal
      conditions for vector development using these approaches, are discussed.

PMID- 11571534
TI  - Generation of adenoviruses encoding the herpes simplex virus vhs gene: a novel
      strategy to generate adenoviruses expressing genes toxic to producer cells.
AB  - Adenovirus vectors expressing suicide genes represent a promising approach for
      cancer gene therapy. We wanted to determine whether the virion host shutoff (vhs)
      gene of herpes simplex virus could be used as a suicide gene for gene therapy of
      glioblastomas. The vhs gene was cloned downstream of the glial fibrillary acidic
      protein promoter to direct tissue-specific expression, and recombinant
      adenoviruses were generated in 293 cells. Viruses, which contained the vhs gene
      but did not express it, could readily be isolated; however, we were unable to
      plaque purify viruses that expressed vhs protein. We constructed a derivative of
      293 cells expressing an antisense RNA to the vhs gene and used them to generate
      adenovirus vectors that express vhs protein. These cells were used to complement
      vhs-expressing adenoviruses through three rounds of plaque purification. This
      approach could be generalized to produce adenovirus vectors expressing other
      toxic transgenes.

PMID- 11571535
TI  - Adenovirus-mediated gene transfer to orthotopic hepatocellular carcinomas in
      athymic nude mice.
AB  - Gene therapy may become an option for the treatment of malignant tumors such as
      hepatocellular carcinoma (HCC), once safe and efficient vector systems have been
      established. Due to their stability in vivo, recombinant adenoviral vectors are
      promising vectors for gene delivery to HCC. To study the characteristics of gene
      delivery into HCCs by recombinant adenoviral vectors in vivo, we established an
      in situ HCC model in the livers of athymic nude mice by intrahepatic injection of
      human HCC cells. Recombinant adenovirus vectors expressing beta-galactosidase
      (Ad2CMV beta gal) were injected via the tail vein of mice bearing HCC or directly
      into intrahepatic tumors. Levels of beta-galactosidase expression in tumor tissue
      and surrounding normal liver were analyzed by histochemistry or for
      quantification by a chemiluminescence assay in tissue homogenates. Following tail
      vein injection, high levels of beta-galactosidase expression were found in the
      liver, but virtually no gene expression could be detected in the tumor tissue. In
      contrast, after direct injection of Ad2CMV beta gal into intrahepatic HCCs, high
      levels of beta-galactosidase expression were detected in the tumor tissue.
      However, single transduced hepatocytes scattered throughout the normal liver
      could also be identified. These results indicate that barriers such as the
      endothelial lining of the tumor vasculature impair the efficiency of adenoviral
      vectors for gene delivery into HCCs by intravenous administration, which can be
      overcome by direct injection into the tumor tissue. However, due to the observed
      transduction of disseminated hepatocytes following intratumoral administration,
      additional HCC-specific targeting to further enhance the safety of adenoviral
      vectors may be required.

PMID- 11571536
TI  - The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced
      by surgical debulking of tumor.
AB  - Malignant mesothelioma (MM) is a solid tumor largely unresponsive to conventional
      therapies. Immunological gene therapy shows promise in murine models and human
      clinical trials; however, the role of surgery in combination with gene therapy
      has not been widely studied. The aim of this study was to determine if debulking
      surgery improved the effectiveness of gene therapy in a murine MM model. Mice
      were subcutaneously inoculated with the MM cell line, AC29, at two different
      sites, 4 days apart, to allow a surgical and distal site tumor to develop. Once
      tumors were established, the surgical site tumor was debulked and vaccination of
      syngeneic tumor transfectants encoding genes for IL-4, IL-2, GM-CSF, B7-1 or
      allogeneic MHC molecules commenced at a site away from both tumors, and tumor
      growth was measured. Neither debulking surgery nor gene therapy alone delayed
      tumor growth. However, there was a clear delay of tumor growth when debulking
      surgery was combined with vaccination of tumor transfectants expressing B7-1 or
      high levels of GM-CSF. Combinations of these two transfectants did not lead to a
      synergistic effect. This study demonstrates that debulking surgery can augment
      the immunostimulatory effects of immunological gene therapy and can delay tumor
      growth. This has implications for the future design of human gene therapy trials
      for solid tumors such as MM.

PMID- 11571537
TI  - Adenovirus-mediated expression of HSV1-TK or Fas ligand induces cell death in
      primary human glioma-derived cell cultures that are resistant to the
      chemotherapeutic agent CCNU.
AB  - Due to minimal treatment success with surgery, radiotherapy, and chemotherapy,
      the aim of this study was to test the therapeutic potential of gene therapy for
      the treatment of glioblastoma multiforme (GBM). We have quantitatively analyzed
      two gene therapy approaches using short-term human glioma cell cultures derived
      from surgical biopsies (designated IN859, IN1612, IN2045, IN1760, and IN1265) and
      compared the results of gene therapy with the chemosensitivity of the same cells.
      All of the glioma cell cultures tested were susceptible to recombinant adenovirus
      (RAd)-mediated infection. Expression of herpes simplex virus type 1-thymidine
      kinase (RAd128), followed by ganciclovir treatment, induced apoptosis in all of
      the glioma cell cultures studied, including three that are resistant to the
      chemotherapeutic drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).
      Expression of murine Fas ligand (RAdhCMV-mFasL) also induced cell death in four
      of the five cell cultures studied. One cell culture that was resistant to CCNU
      was also resistant to apoptosis induced by mFasL expression. These results
      suggest that sensitivity to chemotherapeutic agents does not necessarily
      correlate with the sensitivity to gene therapy treatments. RAds expressing
      therapeutic gene products in human glioma cell cultures are able to induce
      apoptosis even in some cells that are resistant to a commonly used
      chemotherapeutic agent. Therefore, RAd-mediated gene transfer could be a good
      candidate to further develop gene therapy for the treatment of GBM.

PMID- 11571538
TI  - Gene delivery by attenuated Salmonella typhimurium: comparing the efficacy of
      helper versus cytotoxic T cell priming in tumor vaccination.
AB  - Using the murine B16F1 melanoma, we compared a CTL- versus helper T cell (TH)
      directed vaccination approach. Mice were either orally vaccinated with attenuated
      Salmonella typhimurium (SL) or subcutaneously with dendritic cells (DCs) loaded
      with gp100 peptides predicted to bind to H2-Kb/H2-Db molecules. SL were
      transformed with the murine gp100 cDNA (SL-gp100) or with a fusion construct of
      gp100 and a fragment of invariant chain cDNA (SL-gp100/Ii). Transcription of
      these genes in vivo has been readily observed in monocytes and DC. Retardation of
      B16F1 growth was more efficiently achieved by vaccination with SL-gp100 than with
      DC. Vaccination with SL-gp100/Ii aiming at preferential presentation by MHC II
      molecules provided some further improvement due to a stronger expansion of TH and
      CTL. The importance of help was further sustained by a prolongation of the
      survival time when mice concomitantly received IL2. Notably, prophylactic,
      compared to therapeutic, vaccination had no additional impact on survival
      time/rate. This was due to a striking decrease in frequencies of gp100-specific
      TH, CTL, and cytokine-expressing cells during tumor growth. Thus, the efficacy of
      vaccination was limited by tumor-induced immunosuppression. Our data demonstrate
      the oral route of vaccination via Salmonella as a most convenient transfer
      regimen and confirm the superiority of protocols aiming at preferential
      activation of TH.

PMID- 11571539
TI  - Ectopic expression of the thyroperoxidase gene augments radioiodide uptake and
      retention mediated by the sodium iodide symporter in non-small cell lung cancer.
AB  - Radioiodide is an effective therapy for thyroid cancer. This treatment modality
      exploits the thyroid-specific expression of the sodium iodide symporter (NIS)
      gene, which allows rapid internalization of iodide into thyroid cells. To test
      whether a similar treatment strategy could be exploited in nonthyroid
      malignancies, we transfected non-small cell lung cancer (NSCLC) cell lines with
      the NIS gene. Although the expression of NIS allowed significant radioiodide
      uptake in the transfected NSCLC cell lines, rapid radioiodide efflux limited
      tumor cell killing. Because thyroperoxidase (TPO) catalyzes iodination of
      proteins and subsequently causes iodide retention within thyroid cells, we
      hypothesized that coexpression of both NIS and TPO genes would overcome this
      deficiency. Our results show that transfection of NSCLC cells with both human NIS
      and TPO genes resulted in an increase in radioiodide uptake and retention and
      enhanced tumor cell apoptosis. These findings suggest that single gene therapy
      with only the NIS gene may have limited efficacy because of rapid efflux of
      radioiodide. In contrast, the combination of NIS and TPO gene transfer, with
      resulting TPO-mediated organification and intracellular retention of radioiodide,
      may lead to more effective tumor cell death. Thus, TPO could be used as a
      therapeutic strategy to enhance the NIS-based radioiodide concentrator gene
      therapy for locally advanced lung cancer.

PMID- 11571542
TI  - Diagnostic accuracy of computed tomography for cervical metastases at different
      anatomical levels in carcinoma of the tongue.
AB  - OBJECTIVES: To evaluate the variation in diagnostic accuracy of CT in the
      assessment of cervical lymph node metastases from tongue carcinoma at different
      anatomical levels. METHODS: Sixty-one patients with squamous cell carcinoma of
      the tongue who underwent radical neck dissection were included in this study. The
      CT and histopathological findings at nodal levels I-V were compared for the
      presence or absence of lymph node metastases. Sensitivity, specificity, negative
      predictive value (NPV) and positive predictive value (PPV) of CT were evaluated
      for each nodal level. RESULTS: The sensitivity of CT was: level I, 85%; level II,
      77.8%; level III, 53.3%; level IV, 66.7% and level V, 25%. There was a
      significant difference in the sensitivity between the level I-II group (80.9%)
      and level III-V group (53.6%) (P=0.012). There was no significant difference in
      the specificity, NPV, and PPV between the two groups. CONCLUSIONS: The
      sensitivity of CT in detecting cervical lymph node metastases was significantly
      smaller at levels III-V than at levels I-II.

PMID- 11571541
TI  - The relationship of primary tumor thickness in carcinoma of the tongue to
      subsequent lymph node metastasis.
AB  - OBJECTIVES: To study whether primary tumor thickness of stage I/II tongue
      carcinoma provides information about subsequent lymph node metastasis. METHODS:
      Twenty consecutive patients with T1N0M0 or T2N0M0 tongue carcinoma were studied.
      Primary tumor thickness was measured with post-contrast helical computed
      tomography or intra-oral sonography. Cervical lymph nodes were evaluated
      periodically with sonography at intervals of 2-4 weeks. Sensitivity, specificity
      and accuracy for subsequent metastasis was calculated. RESULTS: Positive
      sonographic findings appeared in nine nodes of nine patients during this follow
      up period. Eleven patients underwent neck dissections, and nine had
      histopathologically positive nodes. Nine patients had no sonographic findings of
      metastasis during a minimum follow-up period of 20 months. Primary tumor
      thickness varied from 3-16 mm. Using 5 mm as a cut-off thickness, the
      sensitivity, specificity and accuracy for subsequent lymph node metastasis were
      64, 100 and 75% respectively. CONCLUSIONS: Patients with stage I/II tongue
      carcinoma which is more than 5 mm thick are more likely to develop lymph node
      metastasis.

PMID- 11571543
TI  - Detection of simulated internal tooth resorption using conventional radiography
      and subtraction imaging.
AB  - OBJECTIVES: To compare the diagnostic accuracy of conventional radiography with
      digital subtraction imaging in the detection of simulated internal resorption.
      METHODS: Simulated resorption cavities were created by the sequential use of
      progressively larger round burs (ISO size range 006-016) in the labial wall of
      the coronal or apical thirds of the pulp chamber of the maxillary incisors of two
      cadavers. Five viewers examined 120 pairs of radiographs, one of each pair being
      baseline (no lesion) and the other with or without a lesion. The process was then
      repeated with subtraction images of the pairs of radiographs. Receiver Operating
      Characteristic (ROC) analysis was used to compare the diagnostic accuracy of the
      two imaging modalities. RESULTS: Using conventional radiography, the minimum
      lesion size detectable coronally was in the 'medium' range (ISO size 010 and 012
      round burs), but only 'large' lesions (ISO size 014 and 016) could be detected in
      the apical region. The overall diagnostic accuracy of subtraction imaging was
      superior to conventional radiography but only significant (P<0.05) for coronal
      lesions. CONCLUSION: Subtraction radiography may be a useful tool for detecting
      and monitoring the progress of internal root resorption.

PMID- 11571544
TI  - Comparison of patient dose from imaging protocols for dental implant planning
      using conventional radiography and computed tomography.
AB  - OBJECTIVES: To compare the radiation doses from imaging protocols for dental
      implant planning either using conventional radiography only (dental panoramic
      radiography (DPR), cephalometry and linear cross-sectional tomography) or
      involving computed tomography (CT). METHODS: Organ absorbed doses were measured
      using a female Rando anthropomorphic phantom loaded with lithium fluoride
      thermoluminescent dosemeters (TLD). Standard mandibular protocols for dental
      implant planning were followed using either a conventional dental radiographic
      unit (PM 2002 CC Planmeca, Helsinki, Finland) or CT scanner (Excel Twin Elscint,
      Haifa, Israel). Organ absorbed and effective doses were calculated. Effective
      dose was calculated using two approaches, one based on the ICRP method which
      excludes the salivary tissue from the remainder organs (designated E(exc)), and
      the other with its inclusion (E(inc)). RESULTS: The greatest individual organ
      doses for any examination were measured in the salivary tissue. E(exc) for
      panoramic, cephalometric and cross-sectional tomography using DPR was 0.004 mSv,
      0.002 mSv and 0.002 mSv, respectively, whereas with CT it was 0.314 mSv. The
      value of E(inc) calculated using these data was between two and five times
      E(exc). CONCLUSIONS: E(inc) greatly increases the apparent radiation burden,
      especially with high dose procedures. CT techniques can provide excellent images,
      but at the cost of increased radiation detriment. DPR with a cross-sectional
      tomography facility may give adequate clinical information at a greatly reduced
      dose.

PMID- 11571545
TI  - The use of panoramic radiography in a dental accident and emergency department.
AB  - OBJECTIVES: To determine the rate of appropriate requests for panoramic
      radiography (PR) in a Dental Accident and Emergency Department and the
      implications for patient dose. METHODS: Two hundred and seventy-one requests for
      PR during July 1998 were assessed by two dental radiologists and categorised as
      appropriate or inappropriate based on established selection criteria. Incidental
      findings that might alter patient management were also noted. RESULTS: One
      hundred and fifty-seven requests (58%) were considered appropriate and 114 (42%)
      inappropriate. The most common inappropriate request was to assess disease
      localised to one or two teeth. Dental students were involved in 186 requests and
      76 of these (41%) were inappropriate. The estimated saving in collective
      radiation dose over the month of the study if appropriate radiographs had been
      taken, would have been approximately 540 microSv, a reduction of 70%. Three out
      of 114 (3%) inappropriate, PRS showed minor incidental findings. CONCLUSIONS: A
      considerable proportion of requests for PR were inappropriate. In most of these
      cases, periapical radiographs would have provided more detail with less radiation
      dose. The large number of inappropriate requests involving dental students has
      implications for educators. The use of local selection criteria based on
      currently accepted guidelines would have reduced the dose substantially.

PMID- 11571546
TI  - Comparison of five methods for the derivation of spectra for a constant potential
      dental X-ray unit.
AB  - OBJECTIVES: To compare the diagnostic X-ray spectra derived by different methods
      for a constant potential dental X-ray unit. MATERIALS AND METHODS: Five methods
      of deriving X-ray spectra for a constant potential dental X-ray unit were
      compared: measurement by spectrometer using cadmium-zinc-telluride (CZT)
      detector, calculation by Monte Carlo simulation, calculation by two different,
      semi-empirical methods and estimation from transmission data. The dental X-ray
      set was a Heliodent MD unit (Sirona, Charlotte, NC, USA) operable at 60 or 70 kV.
      A semiconductor detector was used in the spectrometer measurements and an
      ionization chamber dosimeter in the transmission measurements. From the five
      methods, photon-fluence spectra were derived. Based on the photon-fluence
      spectra, average energies and transmission curves in aluminum were calculated.
      RESULTS: For all five methods, the average energies were within 2.4% of one
      another. Comparison of the transmission curves showed an average difference in
      the range of 1 to 6%. CONCLUSION: All of the five methods of deriving spectra are
      in extremely good agreement with each other.

PMID- 11571547
TI  - Fractal dimension on dental radiographs.
AB  - OBJECTIVES: (1) To compare fractal dimension (FD) from periapical radiographs
      with FD from panoramic radiographs; (2) to correlate FD with cortical thickness
      and morphology; and (3) to correlate FD with a reported history of osteoporotic
      fractures. METHODS: Information on fracture and smoking history was obtained by a
      telephone interview with 281 elderly (>60 years of age) patients who had
      periapical and panoramic radiographs exposed on the same date. FD was measured in
      several locations on both types of radiograph. Mandibular cortical thickness and
      morphology were obtained from the panoramic radiograph. RESULTS: FD measured in
      the mandible was lower than FD in the maxilla. Same-jaw measurements had a higher
      correlation than same-side measurements. FD measured on panoramic radiographs was
      lower than FD from periapical radiographs. There was a negative correlation
      between cortical thickness and FD. FD was higher in subjects with more mandibular
      cortical porosities and resorption. The mean panoramic FD from subjects with a
      history of osteoporotic fractures was significantly higher, after adjusting for
      smoking, gender, age, height and weight. CONCLUSIONS: FD measured on panoramic
      radiographs is lower than FD measured on periapical radiographs. FD is higher in
      both types of radiograph in subjects with a thinner, severely eroded mandibular
      cortex and a history of osteoporotic fractures. This study confirms other reports
      that FD increases when bone mass decreases. In addition, it suggests that
      panoramic radiographs can be used as a possible alternative for the measurement
      of FD to periapical radiographs.

PMID- 11571548
TI  - Evaluation of pulse sequences used for magnetic resonance sialography.
AB  - OBJECTIVES: To determine the most appropriate sequences for the visualization of
      small parotid ducts in MR sialography. METHODS: MR images of a phantom consisting
      of distilled water in polyethylene tubes were obtained with turbo-spin echo
      (TSE), single-shot turbo-spin echo (SSTSE), half-fourier acquisition, single-shot
      turbo-spin echo (HASTE) and turbo gradient-spin echo (TGSE) pulse sequences and
      compared visually and quantitatively. MR sialograms obtained from healthy
      volunteers and patients with Sjogren's syndrome (SS) were obtained using the same
      four sequences. RESULTS: In the phantom, TSE images were best and the contrast
      noise ratio (CNR) highest. In the volunteers, the main ducts were especially
      clearly visualized with TSE and in SSTSE; however, the majority of secondary
      and/or tertiary parotid ducts were not depicted by any of the sequences used. In
      SS patients, images of small main ducts and small pseudocysts were clearer using
      TSE. However, TSE could not depict the narrow main ducts or peripheral ducts or
      very small pseudocysts. CONCLUSIONS: TSE is considered the most suitable MR
      sequence for assessing small parotid gland ducts. However, further improvement is
      needed since it does not always visualize them sufficiently.

PMID- 11571549
TI  - Paediatric absorbed doses from rotational panoramic radiography.
AB  - OBJECTIVES: To determine the paediatric doses in rotational panoramic radiography
      with film/screen and photostimulable phosphor receptors. STUDY DESIGN: A
      paediatric anthropomorphic head and neck phantom was used. Absorbed doses were
      measured for two panoramic systems, the Orthophos (Sirona Dental Systems,
      Bensheim, Germany) and the PM 2002 CC (Planmeca Oy, Helsinki, Finland), with and
      without programmable child settings, using both screen/film and photostimulable
      phosphor receptors. RESULTS: Absorbed doses to the eye ranged from 5 to 24 micro
      Gy. Doses to the dental arches with the Orthophos unit ranged from 50 to 555
      micro Gy with the adult and from 27 to 436 micro Gy with the child program; using
      the PM 2002 CC unit, doses ranged from 56 to 1040 micro Gy using the adult
      settings, and from 60 to 890 micro Gy with the paediatric settings. The
      paediatric exposure settings reduced doses at most locations for both panoramic
      systems. The highest doses were measured near the rotational axes of the X-ray
      beam. Paediatric settings with the Orthophos P10 resulted in the dose reduction
      more than 50% to the thyroid but not with the PM 2002 CC. When lower kVcp or mA
      settings were used, absorbed doses were effectively reduced for all combinations
      of machines, programs and detectors. CONCLUSIONS: Specific program settings for
      children reduced the absorbed doses from panoramic radiography irrespective of
      the machine or receptor used.

PMID- 11571550
TI  - Scintigraphic evaluation of chronic osteomyelitis of the mandible in SAPHO
      syndrome.
AB  - A patient with SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and
      osteitis) was evaluated by combined scintigraphy. (99m)Tc HMDP scintigraphy
      showed accumulation in the sternum and lumbar vertebrae as well as the right
      mandible, whereas (67)Ga citrate showed an accumulation in the right mandible,
      but not in the sternum or lumbar vertebrae. These results are consistent with
      chronic osteomyelitis in the mandible.

PMID- 11571551
TI  - Spontaneous regression of a paradental cyst.

PMID- 11571552
TI  - X-linked recessive inheritance of radial ray deficiencies in a family with four
      affected males.
AB  - Radial ray deficiencies are frequently associated with additional clinical
      anomalies and have a heterogeneous aetiology. X-linked forms are extremely rare.
      We report a family in which four male relatives show bilateral absence of the
      radius with presence of the thumbs and associated anomalies. The segregation of
      the phenotype is suggestive for X-linked recessive inheritance. This is confirmed
      by performing linkage analysis using 24 markers spanning the X chromosome in
      which a maximum lod score of 1.93 for DXS8067 and DXS1001 is obtained. We defined
      a critical region of maximal 16.2 cM on the X chromosome with haplotype analysis.

PMID- 11571553
TI  - Refinement of the PARK3 locus on chromosome 2p13 and the analysis of 14 candidate
      genes.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder with clinical
      features of bradykinesia, rigidity, resting tremor and postural instability
      resulting from the deficiency of dopamine in the nigrostriatal system. Previously
      we mapped a susceptibility gene for an autosomal dominant form of PD to a 10.6 cM
      region of chromosome 2p (PARK3; OMIM 602404). A common haplotype shared by two
      North American kindreds (Families B and C) genealogically traced to Southern
      Denmark and Northern Germany suggested a founder effect. Here we report progress
      in the refinement of the PARK3 locus and sequence analysis of candidate genes
      within the region. Members of families B and C were genotyped using polymorphic
      markers, reducing the minimum common haplotype to eight markers spanning a
      physical distance of 2.5 Mb. Analysis of 14 genes within the region did not
      reveal any potentially pathogenic mutations segregating with the disease,
      implying that none of these genes are likely candidates for PARK3.

PMID- 11571554
TI  - Mapping of a new autosomal dominant nonsyndromic hearing loss locus (DFNA30) to
      chromosome 15q25-26.
AB  - Hearing impairment is the most common inherited human sensory defect.
      Nonsyndromic Hearing Impairment (NSHI) is the most genetically heterogeneous
      trait known. Over 70 loci have been mapped and a total of 19 genes have been
      identified. We report here a novel locus (DFNA 30) for autosomal dominant NSHI
      that we mapped to chromosome 15q25-26 in an Italian four-generation family. The
      haplotype analysis has identified a critical interval of 18 cM between markers
      D15S151 and D15S130. This region does not overlap with DFNB16 locus but partially
      coincides with the otosclerosis (OTS) locus. Localisation of the locus DFNA30 is
      a first step towards the identification of the gene.

PMID- 11571555
TI  - Acid-sensing ion channel (ASIC) 4 gene: physical mapping, genomic organisation,
      and evaluation as a candidate for paroxysmal dystonia.
AB  - Acid-sensing ion channels (ASICs) are protongated Na(+) channels. They have been
      implicated with synaptic transmission, pain perception as well as
      mechanoperception. ASIC4 is the most recent member of this gene family. It shows
      expression throughout the central nervous system with strongest expression in
      pituitary gland. ASIC4 is inactive by itself and its function is unknown.
      Mutations in ion channel subunits, which are homologues of ASICs lead to
      neurodegeneration in Caenorhabditis elegans. It has, therefore, been speculated
      that similar mutations in ASICs may be responsible for neurodegeneration in
      humans. Here, we show that ASIC4 maps to the long arm of chromosome 2 in close
      proximity to the locus for paroxysmal dystonic choreoathetosis (PDC), a movement
      disorder with unknown cause. Ion channel genes have been shown to cause several
      other paroxysmal neurologic disorders and are important candidate genes for PDC.
      We established the genomic organisation of the ASIC4 gene and screened a PDC
      pedigree for mutations in the coding region. Although we identified three
      polymorphisms in the Cterminal part of the ASIC4 protein, these were not present
      in each affected subject in the PDC kindred we analysed. Therefore, although the
      ASIC4 gene is physically mapped to the PDC locus, our data indicates that ASIC4
      gene mutation is not the cause of PDC. It remains to be established if mutations
      in ASIC4 or other ASIC subunits may cause neurological disorders.

PMID- 11571556
TI  - Novel PKD1 deletions and missense variants in a cohort of Hellenic polycystic
      kidney disease families.
AB  - The autosomal dominant form of polycystic kidney disease is a very frequent
      genetically heterogeneous inherited condition affecting approximately 1 : 1000
      individuals of the Caucasian population. The main symptom is the formation of
      fluid-filled cysts in the kidneys, which grow progressively in size and number
      with age, and leading to end-stage renal failure in approximately 50% of patients
      by age 60. About 85% of cases are caused by mutations in the PKD1 gene on
      chromosome 16p13.3, which encodes for polycystin-1, a membranous glycoprotein
      with 4302 amino acids and multiple domains. Mutation detection is still a
      challenge owing to various sequence characteristics that prevent easy PCR
      amplification and sequencing. Here we attempted a systematic screening of part of
      the duplicated region of the gene in a large cohort of 53 Hellenic families with
      the use of single-strand conformation polymorphism analysis of exons 16-34. Our
      analysis revealed eight most probably disease causing mutations, five deletions
      and three single amino acid substitutions, in the REJ domain of the protein. In
      one family, a 3-bp and an 8-bp deletion in exons 20 and 21 respectively, were co
      inherited on the same PKD1 chromosome, causing disease in the mother and three
      sons. Interestingly we did not find any termination codon defects, so common in
      the unique part of the PKD1 gene. In the same cohort we identified 11 polymorphic
      sequence variants, four of which resulted in amino acid variations. This supports
      the notion that the PKD1 gene may be prone to mutagenesis, justifying the
      relatively high prevalence of polycystic kidney disease.

PMID- 11571557
TI  - A nonsense mutation is responsible for the RNA-negative phenotype in human
      citrullinaemia.
AB  - Citrullinaemia is an inborn error of metabolism resulting from a deficiency of
      argininosuccinate synthetase. Previous studies of RNA of argininosuccinate
      synthetase of citrullinaemia patients using S1 nuclease analysis have identified
      a class of so-called RNA-negative alleles in which no stable mRNA can be
      detected. To investigate the nature of mutation responsible for such a phenotype,
      a compound heterozygous citrullinaemia carrying an RNA-negative allele and an
      allele with a 3' splice site mutation in intron 6 (IVS6-2A>G) was analysed. Using
      sequences of a DNA polymorphism and the IVS6-2A>G mutation as markers,
      approximately equal amounts of pre-mRNAs from allelic genes were detected
      suggesting that RNA-negative phenotype could not be the result of defect in
      transcription initiation. A C-to-T transition converting the CGA arginine codon
      at residue 279 to a TGA termination codon (R279X) was identified by cDNA
      sequencing. No accumulation of partially spliced pre-mRNAs containing introns
      immediately upstream and downstream of the nonsense mutation was observed. In
      addition, no mRNA species of abnormal size was detected when cDNA from the RNA
      negative allele was analysed. Hence, there is no indication of nonsense
      associated altered splicing (NAS). The most likely event responsible for the RNA
      negative phenotype appears to be nonsense-mediated mRNA decay (NMD).

PMID- 11571558
TI  - Multiple lipomas linked to an RB1 gene mutation in a large pedigree with low
      penetrance retinoblastoma.
AB  - Hereditary predisposition to lipomas is observed in familial multiple lipomatosis
      (OMIM 151900) and benign cervical lipomatosis (OMIM 151800) and can also be
      associated with mutations in the MEN1 and PTEN genes (OMIM 131100 and 153480,
      respectively). In addition, a recent report indicates that a few patients with
      hereditary retinoblastoma also have lipomas. Here we report on an extended family
      segregating a splice site mutation in the RB1 gene. Almost all adult carriers of
      this mutation had multiple lipomas while penetrance for retinoblastoma was
      incomplete. In an unrelated pedigree, which was reported previously, the
      identical mutation was only associated with low-penetrance retinoblastoma but not
      lipomas. Our data indicate that lipoma predisposition in hereditary
      retinoblastoma is not associated with specific RB1 gene mutations but is
      influenced by modifying factors linked to this gene.

PMID- 11571559
TI  - Y-chromosome SNP haplotypes suggest evidence of gene flow among caste, tribe, and
      the migrant Siddi populations of Andhra Pradesh, South India.
AB  - From observations of lack of haplotype sharing based on Y-chromosome specific
      short tandem repeat (STR) loci, previous reports suggested negligible gene flow
      among different geographic populations of India. Using Single Nucleotide
      Polymorphism (SNP) sites in combination with STRs, we observed evidence of
      haplotype sharing across caste-tribe boundaries in South India. We examined 27
      SNPs in the non-recombining region of the Y chromosome to investigate gene flow
      in 204 individuals belonging to three caste groups (Vizag Brahmins, Peruru
      Brahmins, Kammas), three tribes (Bagata, Poroja, Valmiki) and an additional group
      (the Siddis) of African ancestry. Principal component and AMOVA analyses show
      that the between group component of variation is non-significant (P>0.05), while
      that among populations within the caste and tribal groups is significant
      (P<0.001). In particular, the Valmikis and Siddis are close to the caste groups.
      Of a total of 11 distinct SNP-haplotypes observed, the two tribal groups (Bagata
      and Poroja) lack the haplotypes H4, H4A, H5A and H16, which are seen in the caste
      groups. In contrast, all three tribal groups exhibit the Southeast Asian
      haplotype H11 that is absent in the caste populations. The presence of haplotypes
      H4, H5, H14, and H16 in the Siddis indicate that they have assimilated
      considerable non-African admixture. The evidence of haplotype sharing between
      castes and tribes is also found when the H14 lineage was further subdivided by
      five STR loci. We conclude that even though these SNP-based Y-haplotypes are able
      to distinguish the populations, gene flow in these South Indian populations is
      not as negligible as that inferred from other studies based on Y-specific short
      tandem repeat markers.

PMID- 11571560
TI  - Paradoxes in longevity: sequence analysis of mtDNA haplogroup J in centenarians.
AB  - Previous studies have shown that mitochondrial DNA (mtDNA) haplogroup J is
      significantly over-represented in healthy centenarians with respect to younger
      controls, thus suggesting that this haplogroup predisposes to successful aging
      and longevity. On the other hand, the same haplogroup is reported to have
      elevated frequency in some complex diseases. To verify if centenarians clustered
      in a particular lineage within J we have sequenced the D-loop region from 18
      centenarians and 18 younger controls, previously characterized to be J. Then the
      entire mtDNA molecule was sequenced in a sub-sample of nine centenarians to find
      possible functional mutations associated with haplogroup J in successful aging.
      No clustering of the J haplogroup mtDNA from centenarians was observed. In
      addition, most of the mutations found are known as disease-associated mutations.
      The general picture that emerges from the study is that the J haplogroup of
      centenarians is surprisingly similar to that found in complex diseases, as well
      as in Leber Hereditary Optic Neuropathy. This finding implies that the same
      mutations could predispose to disease or longevity, probably according to
      individual-specific genetic backgrounds and stochastic events. This data reveals
      another paradox of centenarians and confirms the complexity of the longevity
      trait.

PMID- 11571561
TI  - Mitochondrial DNA characterisation of European isolates: the Maragatos from
      Spain.
AB  - Mitochondrial DNA analysis confirms that Maragatos from Spain are a genetically
      isolated human group. Genetic distances between Maragatos and the comparison
      samples are significantly different even with the Leon sample (P<0.001) which
      shares the same geographic area as the Maragatos. Although the north-African
      haplogroup U6 is present in them, their attributed Berber origin is weakened, as
      this haplogroup is also detected in surrounding populations with which, in
      addition, Maragatos have the smaller genetic distances. These U6 haplotypes are
      ascribed to a pre-historic African colonisation that influenced all the Iberian
      Peninsula. The presence of Neolithic haplogroups in this sample suggests that
      their isolation culture was not absolute until recent times.

PMID- 11571562
TI  - The evidence of mtDNA haplogroup F in a European population and its ethnohistoric
      implications.
AB  - Mitochondrial DNA polymorphism was analysed in a sample of 108 Croatians from the
      Adriatic Island isolate of Hvar. Besides typically European varieties of human
      maternal lineages, haplogroup F was found in a considerable frequency (8.3%).
      This haplogroup is most frequent in southeast Asia but has not been reported
      before in Europe. The genealogical analysis of haplogroup F cases from Hvar
      suggested founder effect. Subsequent field work was undertaken to sample and
      analyse 336 persons from three neighbouring islands (Brac, Korcula and Krk) and
      379 more persons from all Croatian mainland counties and to determine if
      haplogroup F is present in the general population. Only one more case was found
      in one of the mainland cities, with no known ancestors from Hvar Island. The
      first published phylogenetic analysis of haplogroup F worldwide is presented,
      applying the median network method, suggesting several scenarios how this
      maternal lineage may have been added to the Croatian mtDNA pool.

PMID- 11571563
TI  - Analysis of FMR1 (CGG)(n) alleles and DXS548-FRAXAC1 haplotypes in three European
      circumpolar populations: traces of genetic relationship with Asia.
AB  - Fragile X syndrome, the most common form of inherited mental retardation, is
      caused by expansion of a (CGG)(n) repeat located in the FMR1 gene. The molecular
      factors involved in the mutation process from stable (CGG)(n) alleles towards
      unstable alleles are largely unknown, although family transmission studies and
      population studies have suggested that loss of AGG interruptions in the (CGG)(n)
      repeat is essential. We have analysed the AGG interspersion pattern of the FMR1
      (CGG)(n) repeat and the haplotype distribution of closely located microsatellite
      markers DXS548 and FRAXAC1, in three circumarctic populations: Norwegians, Nenets
      and Saami. The data confirm the conservation, reported in all human populations
      studied so far, of an AGG interruption for each 9-10 CGG and support the
      stabilising effect of AGG interruptions. The data also indicate the existence of
      chromosomes of Asian origin in the Saami and Nenets population, thereby
      confirming a genetic relationship between Northern Europe and Asia. DXS548
      FRAXAC1 haplotype frequencies were compared between 24 Norwegian fragile X males
      and 119 normal males. Significant linkage disequilibrium were found between the
      fragile X mutation and haplotype 6-4 and between normal (CGG)(n) alleles and
      haplotype 7-3.

PMID- 11571564
TI  - Development of formulations that enhance physical stability of viral vectors for
      gene therapy.
AB  - This study summarizes our initial efforts to address an issue that is critical to
      the success of any multicenter gene therapy clinical trial - maintenance of
      vector viability during shipping and storage at remote test sites. We have
      identified formulation and processing factors that influence stability of viral
      preparations such as selection of appropriate buffer systems, cryoprotectants,
      and storage conditions. Adenovirus and adeno-associated virus expressing E. coli
      beta-galactosidase (lacZ) were suspended in blends of complex carbohydrates,
      cyclodextrins and various surfactants. X-gal stains of 293 and 84-31 cells were
      used to determine infectious titer of all preparations. Potassium phosphate
      buffered preparations consistently maintained high viral titers after storage at 
      20 and 4 degrees C. Blends of sucrose, mannitol, and surfactant showed negligible
      loss of titer for 35 days at 4 degrees C. Formulations of sucrose and
      cyclodextrin were stable for 2 years at -20 degrees C. Negligible loss in titer
      was observed in unit-dose viral preparations lyophilized in sucrose and stored at
      4 degrees C for 1 year after an initial loss of 0.5 log due to processing.
      Studies with lyophilized sucrose/mannitol blends have shown that viral recovery
      after processing is directly related to the final moisture content of the dried
      product. Virus concentration also plays a significant role in recovery after
      processing with highly concentrated preparations showing minimal loss in titer
      after lyophilization. In summary, lyophilized preparations that can be shipped
      and stored at 25 degrees C offer a solution to the current problem of
      distribution of viral vectors for clinical trials.

PMID- 11571565
TI  - Prevention of systemic clinical disease in MPS VII mice following AAV-mediated
      neonatal gene transfer.
AB  - For many inborn errors of metabolism, early treatment is critical to prevent long
      term developmental sequelae. We have previously shown that systemic treatment of
      neonatal mucopolysaccharidosis type VII (MPS VII) mice with recombinant adeno
      associated virus (AAV) vectors results in relatively long-term expression of beta
      glucuronidase (GUSB) in multiple tissues, and a reduction in lysosomal storage.
      Here, we demonstrate that therapeutic levels of enzyme persist for at least 1
      year following a single intravenous injection of virus in neonatal MPS VII mice.
      The level and distribution of GUSB expression achieved is sufficient to prevent
      the development of many aspects of clinical disease over the life of the animal.
      Following treatment, bone lengths, weights and retinal function were maintained
      at nearly normal levels throughout the life of the animal. In addition,
      significant improvements in survival and auditory function were seen in AAV
      treated MPS VII mice when compared with untreated mutant siblings. These data
      suggest that AAV-mediated gene transfer in the neonatal period can lead to
      prevention of many of the clinical symptoms associated with MPS VII in the murine
      model of this disease.

PMID- 11571566
TI  - Stable therapeutic serum levels of human alpha-1 antitrypsin (AAT) after portal
      vein injection of recombinant adeno-associated virus (rAAV) vectors.
AB  - Previous work from our group showed that recombinant adeno-associated virus
      (rAAV) vectors mediated long-term secretion of therapeutic serum levels of human
      alpha-1 antitrypsin (hAAT) after a single injection in murine muscle. We
      hypothesized that hepatocyte transduction could be even more efficient, since
      these cells represent the natural site of AAT production and secretion. To test
      this hypothesis, rAAV vectors containing the hAAT cDNA driven by either the human
      elongation factor 1 alpha promoter, the human cytomegalovirus immediate-early
      promoter (CMV), or the CMV-chicken beta actin hybrid (CB) promoter were injected
      into the portal or tail veins of adult C57Bl/6 mice. Potentially therapeutic
      serum levels of hAAT (600 microg/ml) were achieved after portal vein injection of
      doses of 4 x 10(9) infectious units (IU), a 10-fold lower dose than that required
      for similar levels of expression via the i.m. route. Serum levels greater than 1
      mg/ml were achieved at doses of 3 x 10(10) IU. Southern blotting of liver DNA
      revealed the presence of circular episomal vector genomes. Immunostaining showed
      that transgene expression was scattered throughout the liver parenchyma. Similar
      results were obtained with a rAAV-CB-green fluorescent protein (GFP) vector.
      There was no evidence of hepatic toxicity. These data indicate that liver
      directed rAAV-based gene therapy is effective in the murine model, and hence
      might be feasible for treatment of human AAT deficiency.

PMID- 11571567
TI  - Recombinant Semliki Forest virus vaccine vectors: the route of injection
      determines the localization of vector RNA and subsequent T cell response.
AB  - Vectors based on Semliki Forest virus (SFV) have been widely used in vitro and in
      vivo to express heterologous genes in animal cells. In particular, the ability of
      recombinant SFV (rSFV) to elicit specific, protective immune responses in animal
      models suggests that rSFV may be used as a vaccine vehicle. In this study, we
      examined the distribution of rSFV in vivo by immunohistochemistry and RT-PCR
      after intravenous, intramuscular and subcutaneous injection of rSFV particles and
      related this to the degree of cytotoxic T lymphocyte (CTL) responses and
      frequency of specific T cells detected by MHC-I tetramers. We found that after
      i.v. injection, rSFV-RNA was distributed to a variety of different tissues,
      whereas it was confined locally after i.m. and s.c. injections. The persistence
      of the rSFV vector was transient, and no viral RNA could be detected 10 days
      after inoculation. All tested routes of immunization generated significant levels
      of antigen-specific CTL responses and increased numbers of specific CD8+ T cells,
      as detected by tetramer binding. The distribution of antigen-specific CTLs
      correlated with the in vivo distribution pattern of rSFV, with a highest
      frequency in the spleen or local lymph node, depending on the injection route.

PMID- 11571568
TI  - AV.TK-mediated killing of subcutaneous tumors in situ results in effective
      immunization against established secondary intracranial tumor deposits.
AB  - Gene transfer vectors expressing herpes simplex thymidine kinase (HSVtk), in
      addition to direct killing of tumor cells, often have an associated local
      "bystander effect" mediated by metabolic coupling of tumor cells. A systemic
      antitumor effect mediated by the immune system, termed the distant bystander
      effect, has also been reported. We have observed the development of cytotoxic T
      lymphocyte (CTL) populations and long-lasting antitumor immunity following
      treatment of subcutaneous tumors with an adenoviral vector expressing HSVtk
      (AV.TK) and ganciclovir (GCV) in rat glioma model. This vaccination effect seen
      with AV.TK/GCV treatment of subcutaneous tumor could even abrogate or retard
      growth of previously established secondary intracranial tumors.

PMID- 11571569
TI  - Quantitative comparison of expression with adeno-associated virus (AAV-2) brain
      specific gene cassettes.
AB  - This study compared a range of mammalian CNS expression cassettes in recombinant
      adeno-associated virus (AAV-2) vectors using strong endogenous promoter
      sequences, with or without a strong post-regulatory element and polyadenylation
      signal. Changes in these elements led to transgene expression varying by over
      three orders of magnitude. In experiments conducted in primary cell culture and
      in >100 stereotactically injected rats, we observed highly efficient and stable
      (>15 months) gene expression in neurons and limited expression in glia; the
      highest expression occurred with endogenous, nonviral promoters such as neuron
      specific enolase and beta-actin. The packaging size of AAV-2 was maximized at 5.7
      kb without impairing gene expression, as judged by direct comparison with a
      number of smaller AAV-2 constructs. The genomic insert size and titer were
      confirmed by Southern blot and quantitative PCR, and infectivity was tested by
      particle titer using ELISA with a conformation-dependent epitope that requires
      the full intact capsid. A packaging and purification protocol we describe allows
      for high-titer, high-capacity AAV-2 vectors that can transduce over 2 x 10(5)
      neurons in vivo per microliter of vector, using the strongest expression
      cassette.

PMID- 11571570
TI  - Intrasplenic transplantation of IL-18 gene-modified hepatocytes: an effective
      approach to reverse hepatic fibrosis in schistosomiasis through induction of
      dominant Th1 response.
AB  - Hepatic fibrosis is a common outcome of chronic liver diseases. In
      schistosomiasis, chronic parasite egg-induced granuloma formation can lead to
      fibrosis, which is immunologically characterized by the dominant Th2 response.
      Recently, it has been shown that gene therapy is an attractive approach for the
      treatment of hepatic fibrosis. To investigate the antifibrotic effects of IL-18
      gene transfer, a normal murine liver cell line BNL.CL2 was transfected with
      recombinant adenovirus encoding mouse IL-18, and then intrasplenically
      transplanted into mice infected with Schistosoma japonicum (S. japonicum). Our
      data show that IL-18 gene-modified hepatocytes intrasplenically transplanted into
      mice can effectively express IL-18 in the liver and in peripheral blood.
      Intrasplenic transplantation of IL-18 gene-modified hepatocytes into S. japonicum
      infected mice could result in a significantly increased IFN-gamma and IL-2 but
      decreased IL-4 and IL-10 concentration both in the liver and in the serum,
      suggesting that the dominant Th2 response in mice with schistosomiasis could be
      reversed by this intervention. Consistent with the changes in Th1 and Th2
      cytokine production, mice intrasplenically transplanted with IL-18 gene-modified
      hepatocytes developed much less hepatic fibrosis at 20 weeks after infection,
      which was evaluated by liver content of hydroxyproline, collagens, and hepatic
      mRNA expression of procollagens. These data indicate that intrasplenic
      transplantation of IL-18 gene-modified hepatocytes can be a candidate for
      therapeutic intervention in hepatic fibrosis through induction of a dominant Th1
      response.

PMID- 11571571
TI  - Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors.
AB  - Gene therapy using recombinant adeno-associated virus vectors (rAAV) is generally
      considered safe. During the course of a study designed to determine the long-term
      efficacy of rAAV-mediated gene therapy initiated in newborn mice with the
      lysosomal storage disease, mucopolysaccharidosis type VII (MPSVII), a significant
      incidence of hepatocellular carcinomas and angiosarcomas was discovered. A
      hepatocellular carcinoma was first detected in a 35-week-old mouse and by 72
      weeks of age, three out of five rAAV-treated MPSVII mice had similar lesions.
      These types of tumors had not been seen previously in long-term studies of MPSVII
      mice using recombinant enzyme or bone marrow transplantation. In an attempt to
      ascertain whether mouse strain or GUSB expression confers susceptibility to tumor
      formation, we histopathologically examined untreated normal mice of the same
      strain, untreated MPSVII mice, and normal mice overexpressing human GUSB for the
      presence of tumors and increased hepatocyte replication. The results of these
      studies do not indicate that MPSVII mice or mice overexpressing human GUSB are
      susceptible to tumor formation; however, the number of animals examined is too
      small to draw definitive conclusions. Results from quantitative PCR performed on
      the tumor samples suggest that the tumors are probably not caused by an
      insertional mutagenesis event followed by the clonal expansion of a transformed
      cell. In a separate study, a relatively large group of mice injected with varying
      doses and types of rAAV vectors had no evidence of hepatic or vascular tumors.
      Although the mechanism of tumor formation is currently unknown, the tumorigenic
      potential of rAAV vectors must be rigorously determined in long-term in vivo
      studies.

PMID- 11571572
TI  - CAR-binding ablation does not change biodistribution and toxicity of adenoviral
      vectors.
AB  - Intravenous administration of adenoviral vectors results mostly in hepatocyte
      transduction and subsequent hepatotoxicity. Because hepatocytes express high
      levels of the primary adenovirus receptor CAR, untargeting hepatocytes requires
      CAR-binding ablation. The amino acid residues of the viral fiber responsible for
      CAR-binding are known. We have constructed a mutant adenoviral vector unable to
      bind CAR and studied vector biodistribution and hepatotoxicity after intravenous
      administration. In contrast to a vector with wild-type fiber, the infectivity of
      the CAR-ablated vector is greatly reduced and not susceptible to inhibition with
      wild-type knob. Biodistribution and hepatotoxicity are, however, not affected by
      CAR-binding ablation. A possible explanation could be related to an increased
      blood persistence detected for the CAR-ablated vectors combined with their
      residual infectivity through other receptors.

PMID- 11571573
TI  - Intramuscular plasmid DNA injection can accelerate autoimmune responses.
AB  - We have investigated if the administration of plasmid vectors engineered for gene
      delivery into mammalian muscle induced the production of anti-double stranded
      (ds) DNA and anti-nuclear autoantibodies in normal and autoimmunity-prone mouse
      models. In normal mice, repeated injection of plasmid DNA did not trigger an anti
      DNA response. The presence of eukaryotic transcription factor binding sites in
      plasmid vectors did not increase autoantibody formation in these animals. In
      contrast, repeated injection of such plasmids in autoimmunity-prone MRL/MpJ mice
      caused a significant increase in both anti-dsDNA and anti-nuclear antibody
      levels. Thus the repeated administration of bacterial plasmids containing
      eukaryotic promoter elements may induce immune responses with generation of
      antibodies cross-reacting not only with the mammalian DNA, but also with nuclear
      antigens. The potential for iatrogenic autoimmunity in susceptible individuals
      should be considered.

PMID- 11571574
TI  - Hypoxia-inducible transgene expression in differentiated human NT2N neurons--a
      cell culture model for gene therapy of postischemic neuronal loss.
AB  - Expression of anti-apoptotic or neurotrophic transgene proteins in hypoxic
      neurons may provide a novel therapeutic strategy for neuroprotection and
      alleviation of damage to ischemic brain areas. NT2, a human neoplastic cell line
      which terminally differentiates into postmitotic neurons (NT2N) by treatment with
      retinoic acid was used in this study as a cell culture model for human neuronal
      cells. The hypoxia-inducible VEGF promoter in plasmid vectors was employed to
      drive the expression of marker genes (luciferase) and therapeutic genes (bcl2) in
      hypoxic NT2 cells and NT2N neurons in culture. Cationic liposomes complexed with
      plasmid DNA were used for transfection of vectors with the constitutive
      cytomegalovirus promoter (pCMV) or the hypoxia-inducible VEGF promoter (pHRE).
      Hypoxic or normoxic control NT2 cells transfected with pCMV-luciferase showed
      high transgene expression (2.4 x 10(8) relative light units (RLU)/mg protein).
      Control NT2 cells transfected with pHRE-luciferase had a rather low activity (4.9
      x 10(6) RLU/mg protein), which was induced 34-fold under hypoxic conditions. Four
      fold induction of luciferase expression was obtained in hypoxic NT2N neurons
      transfected with pHRE compared with normoxic controls. The hypoxia-induced
      luciferase expression in NT2N cells was 34% of the activity of pCMV-luciferase
      under the same conditions. Transfection of NT2N neurons with pCMV-bcl2 or pHRE
      bcl2 was demonstrated to reduce significantly the numbers of apoptotic cells
      after hypoxia. These results demonstrate efficient VEGF promoter-mediated
      induction of transgene expression in hypoxic human neurons. This cell culture
      model may be employed for the further investigation of therapeutic proteins
      against ischemic brain damage due to neuronal loss.

PMID- 11571575
TI  - Prostate-specific expression of Bax delivered by an adenoviral vector induces
      apoptosis in LNCaP prostate cancer cells.
AB  - In prostate carcinoma, overexpression of the anti-apoptotic gene Bcl-2 has been
      found to be associated with resistance to therapies including radiation and
      androgen ablation. Restoring the balance of Bcl-2 family members may result in
      the induction of apoptosis in prostate cancer cells previously resistant to
      treatment. To accomplish this, a strategy involving overexpression of the pro
      apoptotic gene Bax was executed. The use of cytotoxic genes such as Bax require
      selective expression of the gene. In this study, we examined the ability of
      selective expression of Bax protein directed by a prostate-specific promoter to
      induce apoptosis in human prostate carcinoma. A second-generation adenoviral
      vector was constructed with the modified prostate-specific probasin promoter,
      ARR2PB, directing expression of an HA-tagged Bax gene and a green fluorescent
      protein reporter translated from an internal ribosome entry site
      (ARR2PB.Bax.GFP). ARR2PB promoter activity is tightly regulated and highly
      prostate specific and is responsive to androgens and glucocorticoids. The
      prostate-specific promoter-Bax-GFP transgene cassette was inserted into a cloning
      site near the right inverted terminal repeat of the adenoviral vector to retain
      specificity of the promoter. LNCaP cells infected with Ad/ARR(2)PB.Bax.GFP showed
      high levels of Bax expression 48 h after infection resulting in an 85% reduction
      in cell viability. Importantly, LNCaP cells stably transfected to overexpress Bcl
      2 showed similar patterns of cell death when infected with Ad/ARR(2)PB.Bax.GFP,
      an 82% reduction in cell viability seen 48 h after infection. Apoptosis was
      confirmed by measuring caspase activation and using the TUNEL assay. Tissue
      specificity was evaluated using A549 cells (lung adenocarcinoma), SK-Hep-1 (liver
      cancer) cells, and Hela (cervical cancer) cells which did not show detectable
      expression of virally delivered Bax protein or any increase in cell death.
      Systemic administration of Ad/ARR2PB. Bax.GFP in nude mice revealed no toxicity
      in liver, lung, kidney, or spleen. This study shows that infection with the
      second-generation adenovirus, ARR2PB.Bax.GFP, results in highly specific
      cytotoxicity in LNCaP cells, and that consequent overexpression of Bax in
      prostate carcinoma, even in the context of high levels of Bcl-2 protein, resulted
      in apoptosis. These results suggest that a second-generation adenovirus-mediated,
      prostate-specific Bax gene therapy is a promising approach for the treatment of
      prostate cancer.

PMID- 11571576
TI  - Viral vector-mediated expression of K+ channels regulates electrical excitability
      in skeletal muscle.
AB  - Modification of K+ currents by exogenous gene expression may lead to therapeutic
      interventions in skeletal muscle diseases characterized by alterations in
      electrical excitability. In order to study the specific effects of increasing
      outward K+ currents, we expressed a modified voltage-dependent K+ channel in
      primary cultured rat skeletal muscle cells. The rat Kv1.4 channel was expressed
      as an N-terminal fusion protein containing a bioluminescent marker (green
      fluorescent protein). Transgene expression was carried out using the helper
      dependent herpes simplex 1 amplicon system. Transduced myoballs, identified using
      fluorescein optics and studied electrophysiologically with single-cell patch
      clamp, exhibited a greater than two-fold increase in K+ conductance by 20-30 h
      after infection. This increase in K+ current led to a decrease in membrane
      resistance and a 10-fold increase in the current threshold for action potential
      generation. Electrical hyperexcitability induced by the Na+ channel toxin anemone
      toxin II (1 microM) was effectively counteracted by overexpression of Kv1.4 at 30
      32 h after transduction. Thus, virally induced overexpression of a voltage-gated
      K+ channel in skeletal muscle has a powerful effect in reducing electrical
      excitability.

PMID- 11571577
TI  - Mucus altering agents as adjuncts for nonviral gene transfer to airway
      epithelium.
AB  - Nonviral vectors have been shown to be a safe and valid alternative to
      recombinant viruses for gene therapy of cystic fibrosis (CF). Nevertheless, gene
      transfer efficiency needs to be increased before clinical efficacy is likely in
      man. One barrier to increased efficacy is normal airway mucus. Using an ex vivo
      model of sheep tracheal epithelium, we show that this barrier can, in part, be
      overcome by treatment with the mucolytic agents, Nacystelyn or N-acetylcysteine
      using either a cationic lipid or a cationic polymer as the gene transfer agent.
      Further, in vivo application of either Nacystelyn or the anticholinergic
      glycopyrrolate, both clinically used agents, resulted in increased reporter gene
      expression in the mouse lung, but no significant correction of the bioelectric
      defect in CF null mice. These results, whilst unlikely to be sufficient in
      themselves to achieve clinically relevant gene therapy, may be a further useful
      step in the attainment of this goal.

PMID- 11571578
TI  - Transfection of large plasmids in primary human myoblasts.
AB  - The ex vivo gene therapy approach for Duchenne muscular dystrophy is promising
      since myoblast transplantation in primates is now very efficient. One obstacle to
      this treatment is the low transfection efficiency of large DNA constructs in
      human primary myoblasts. Small plasmids can be easily transfected with the new
      phosphonolipid described in this study. However, a dramatic drop in transfection
      efficiency is observed with plasmids of 12 kb or more containing EGFP
      minidystrophin and EGFP dystrophin fusion genes. The transfection of human
      primary myoblasts with such large plasmids could only be achieved when the DNA
      was linked to an adenovirus with the use of polyethylenimine (PEI), with
      efficiencies ranging between 3 and 5% of transitory transfection. Branched 2 kDa
      PEI was less toxic in PEI adenofection than branched 25 kDa PEI or linear 22 kDa
      PEI. The adenovirus was an absolute necessity for an efficient transfection. An
      integrin-binding peptide, a nuclear localization signal peptide, chloroquine,
      glycerol or cell cycle synchronization using aphidicolin did not enhance PEI
      adenofection. Following PEI adenofection, the adenoviral proteins were detected
      using a polyclonal antibody. The detected antigens fell below the detectable
      level after 12 days in culture. We thus provide in this study an efficient and
      reproducible method to permit efficient delivery of large plasmids to human
      primary myoblasts for the ex vivo gene therapy of Duchenne muscular dystrophy.

PMID- 11571579
TI  - Immune-mediated destruction of transfected myocytes following DNA vaccination
      occurs via multiple mechanisms.
AB  - The delivery of antigenic proteins in the context of a DNA vaccine leads to the
      intracellular synthesis of antigen and the induction of both humoral and cellular
      immune responses. Subsequent to immune activation, any transfected cell
      expressing the immunogenic protein should, by the rules of immunology, become a
      legitimate target for removal by immune-mediated mechanisms. Herein, we have used
      an indirect assay of myocyte integrity following intra-muscular (i.m.) delivery
      of a DNA vaccine, in mice with various immune deficiencies, to determine which
      immunological mechanisms may be involved in destruction of antigen-expressing
      cells. We demonstrate that destruction of antigen- expressing myocytes following
      i.m. injection of a DNA vaccine is dependent on major histocompatibility complex
      (MHC) class II restricted CD4+ T cell activation, but is not mediated solely by
      MHC I-restricted or perforin-mediated lysis and appears to have a component that
      is antibody-mediated. Although we studied myocytes, the results likely represent
      what happens to any transfected cell expressing a foreign antigen. This study
      underscores the ability of DNA vaccines at inducing antigen-specific immune
      responses that include a number of effector mechanisms. From the perspective of
      gene therapy, this study highlights the significance of immune activation when
      considering strategies where maintenance of therapeutic gene expression is
      desired.

PMID- 11571581
TI  - Liposomal IGF-1 gene transfer modulates pro- and anti-inflammatory cytokine mRNA
      expression in the burn wound.
AB  - The use of systemic IGF-1 has been shown to attenuate the postburn hypermetabolic
      response and improve burn wound healing. Local IGF-1 gene therapy, however,
      promotes re-epithelialization in the burn wound without the side-effects
      associated with systemic delivery. We tested the hypothesis that these beneficial
      effects are due to changes in local cytokine production. Adult male Sprague
      Dawley rats received a 40% total body surface area full-thickness scald burn and
      randomly received a subcutaneous injection at the burn wound margin of saline or
      cationic liposomes containing a IGF-1 cDNA construct. Animals were killed at 1,
      4, 7 and 10 days after burn trauma. Skin biopsies at the wound border were
      harvested for total RNA extraction. Cytokine mRNA expression was determined using
      a multi-probe RNase protection assay. Data are presented as means +/- s.e.m.
      Statistical analysis used the unpaired t-test or Mann-Whitney test where
      appropriate. Significance was accepted at P < 0.05. Treatment of the burn wound
      with liposomal IGF-1-cDNA transfer decreased IL-1beta mRNA levels on day 10 after
      burn trauma from five-fold burn-induced increases compared with sham-treated
      rats, to near the control values present in unburned skin samples. Similarly,
      there was an eight-fold increase in TNF-alpha mRNA expression on postburn day 10
      that was abrogated by IGF-1 gene therapy. Local IGF-1 gene transfer attenuates
      the mRNA expression of the inflammatory cytokines IL-1beta and TNF-alpha in the
      burn wound. This change may improve burn wound healing by decreasing prolonged
      local inflammation.

PMID- 11571580
TI  - Adenovirus-mediated transfer of the p53 family genes, p73 and p51/p63 induces
      cell cycle arrest and apoptosis in colorectal cancer cell lines: potential
      application to gene therapy of colorectal cancer.
AB  - p53 gene therapy is being tested clinically for the treatment of human cancer,
      however, some cancer models (in vivo and in vitro) are resistant to p53. To
      explore the potential use of two p53 homologues, p73 and p51/p63, in cancer gene
      therapy, we introduced p53, p73 and p51/p63 into colorectal cancer cell lines via
      adenoviral vectors, and compared their effects on cell growth. Among 10 cell
      lines tested, six cell lines displayed a similar response following transduction
      of p53, p73beta or p51A/p63gamma; two lines underwent cell-cycle arrest, three
      lines exhibited apoptosis and one line showed no-effect following transduction.
      The effect on cell-cycle progression was variable in the other four cell lines.
      Interestingly, three cell lines were resistant to p53-mediated apoptosis,
      including two lines having endogenous wild-type p53 alleles, but underwent
      apoptosis after transduction of p73beta or p51A/p63gamma. Similar to p53,
      transduction of p51A/p63gamma induced extensive apoptosis when combined with
      adriamycin or X-radiation in SW480 cells, which are normally resistant to
      apoptosis. Transduction of p73beta and p51A/p63gamma also reduced the
      tumorigenicity of two colorectal cancer cells in vivo. These results suggest that
      adenovirus-mediated p73beta and p51A/p63gamma transfer are potential novel
      approaches for the treatment of human cancers, particularly for tumors that are
      resistant to p53 gene therapy.

PMID- 11571582
TI  - Chimeric PSA enhancers exhibit augmented activity in prostate cancer gene therapy
      vectors.
AB  - The native PSA enhancer and promoter confer prostate-specific expression when
      inserted into adenovirus vectors capable of efficient in vivo gene delivery,
      although the transcriptional activity is low. By exploiting properties of the
      natural PSA control regions, we have improved the activity and specificity of the
      prostate-specific PSA enhancer for gene therapy and imaging applications.
      Previous studies have established that androgen receptor (AR) molecules bind
      cooperatively to AREs in the PSA enhancer core (-4326 to -3935) and act
      synergistically with AR bound to the proximal promoter to regulate
      transcriptional output. To exploit the synergistic nature of AR action we
      generated chimeric enhancer constructs by (1) insertion of four tandem copies of
      the proximal AREI element; (2) duplication of enhancer core; or (3) removal of
      intervening sequences (-3744 to -2855) between the enhancer and promoter. By
      comparing to the baseline construct, PSE, containing the PSA enhancer (-5322 to 
      2855) fused to the proximal promoter (-541 to +12), the three most efficacious
      chimeric constructs, PSE-BA (insertion of ARE4), PSE-BC (duplication of core) and
      PSE-BAC (insertion of core and ARE4), are 7.3-, 18.9-, and 9.4-fold higher,
      respectively. These chimeric PSA enhancer constructs are highly androgen
      inducible and retain a high degree of tissue discriminatory capability. Initial
      biochemical studies reveal that the augmented activity of the chimeric constructs
      in vivo correlates with their ability to recruit AR and critical co-activators in
      vitro. The enhanced activity, inducibility and specificity of the chimeric
      constructs are retained in an adenoviral vector (Ad-PSE-BC-luc). Systemic
      administration of Ad-PSE-BC-luc into SCID mice harboring the LAPC-9 human
      prostate cancer xenografts shows that this prostate specific vector retained
      tissue discriminatory capability compared with a comparable cytomegalovirus (CMV)
      promoter driven vector.

PMID- 11571583
TI  - Pre-clinical evaluation of an in vitro selection protocol for the enrichment of
      transduced CD34+ cell-derived human dendritic cells.
AB  - The efficient genetic modification of CD34+ cell-derived dendritic cells (DC)
      will provide a significant advancement towards the development of immunotherapy
      protocols for cancer, autoimmune disorders and infectious diseases. Recent
      reports have described the transduction of CD34+ cells via retrovirus- and
      lentivirus-based gene transfer vectors and subsequent differentiation into
      functional DC. Since there is significant apprehension regarding the clinical
      uses of HIV-based vectors, in this report, we compare a murine leukemia virus
      (MLV)- and a human immunodeficiency virus (HIV)-based bicistronic vector for gene
      transfer into human CD34+ cells and subsequent differentiation into mature DC.
      Each vector expressed both EGFP and the dominant selectable marker DHFR(L22Y)
      allowing for the enrichment of marked cells in the presence of the antifolate
      drug trimetrexate (TMTX). Both MLV-based and HIV-based vectors efficiently
      transduced cytokine mobilized human peripheral blood CD34+ cells. However, in
      vitro expansion and differentiation in the presence of GM-CSF, TNF-alpha, Flt-3L,
      SCF and IL-4 resulted in a reduction in the percentage of DC expressing the
      transgene. Selection with TMTX during differentiation increased the percentage of
      marked DC, resulting in up to 79% (MLV vector) and up to 94% (lentivirus-vector)
      transduced cells expressing EGFP without loss of DC phenotype. Thus, MLV-based
      vectors and in vitro selection of transduced human DC show great promise for
      immunotherapy protocols.

PMID- 11571584
TI  - Activation of NF-kB mediates ICAM-1 induction in respiratory cells exposed to an
      adenovirus-derived vector.
AB  - Gene transfer to the respiratory tract by replication-deficient adenoviruses is
      limited by the induction of inflammatory and immune responses. We previously
      demonstrated that a E1-E3-deleted recombinant adenovirus carrying the expression
      cassette for the cystic fibrosis gene (Ad.CFTR) upregulates the expression of the
      pro-inflammatory intercellular adhesion molecule-1 (ICAM-1) both in vitro and in
      vivo. In the present work we suggest a role for the nuclear factor-kB (NF-kB) in
      Ad.CFTR-dependent up-regulation of ICAM-1 in respiratory epithelial A549 cells.
      Specifically, Ad.CFTR induced translocation of NF-kB into the nucleus and binding
      to the proximal -228/-218 NF-kB consensus sequence on the ICAM-1 promoter.
      Ad.CFTR also stimulated a 13-fold increase in NF-kB-dependent expression of the
      CAT reporter gene under the control of a region of the ICAM-1 promoter, including
      the proximal NF-kB consensus sequence. The Ad.CFTR-dependent increase of ICAM-1
      mRNA was abolished by inhibitors of NF-kB, such as N-acetyl-L-cysteine,
      pyrrolidine dithiocarbamate, parthenolide and the synthetic peptide SN50. All
      these inhibitors abolished both Ad.CFTR-induced NF-kB DNA binding and
      transactivating activities. These results indicate a critical role of NF-kB in
      the pro-inflammatory response elicited by replication-deficient adenoviral
      vectors in respiratory cells.

PMID- 11571585
TI  - Michael J Stock (1942-2001): an appreciation.

PMID- 11571586
TI  - Thermogenesis: where are we and where are we going? Report of a workshop held in
      London 21st April 2001, convened by Professor Mike Stock.

PMID- 11571587
TI  - Adipose tissues display differential phagocytic and microbicidal activities
      depending on their localization.
AB  - OBJECTIVE AND DESIGN: We recently reported that white preadipocytes phagocyte and
      kill micro-organisms, suggesting an active involvement of fat cells in host
      defence. Since characteristics of adipose tissues vary according to their
      localization, we measured the phagocytic capacity of stromal-vascular fraction
      (SVF) cells from different pads of white and brown adipose tissue in primary
      culture. RESULTS: The microbicidal activities of SVF cells in inguinal and
      epididymal white depots were similar, but much higher than in brown fat pad.
      Considering the whole pad, the highest cytotoxic potential was found in inguinal
      white adipose tissue (WAT) depot, whereas interscapular brown adipose tissue
      (BAT) showed an extremely low ability to kill micro-organisms. These differences
      might be mainly attributed to preadipocyte activities, with regard to the low
      content in resident macrophages identified by their expression of F4/80 antigen.
      CONCLUSIONS: Taken together these results suggest that the role as macrophage
      like cells for cells of the fat stroma-vascular fraction, among which
      preadipocytes, is not negligible. This emphasizes the relationship existing
      between inflammatory and adipose cells. A differential responsiveness of adipose
      pads to infections and inflammatory situations due to the specific phagocytic
      ability of their SVF cells was thus proposed.

PMID- 11571588
TI  - Effects of beacon administration on energy expenditure and substrate utilisation
      in Psammomys obesus (Israeli sand rats).
AB  - OBJECTIVE: To investigate whether beacon administration affects substrate
      utilisation, physical activity levels or energy expenditure in Psammomys obesus.
      DESIGN: Pairs of age- and sex-matched Psammomys obesus were randomly assigned to
      either beacon-treated (15 microg/day for 7 days (i.c.v.)) or control (i.c.v.
      saline) groups. MEASUREMENTS: Indirect calorimetry on day 0 and day 7 to measure
      oxygen consumption and carbon dioxide production, which were used to calculate
      fat oxidation, carbohydrate oxidation and total energy expenditure. Physical
      activity in the calorimeter was measured using an infrared beam system. Food
      intake and body weight were measured daily. RESULTS: The administration of beacon
      significantly increased body weight compared to saline-treated control animals.
      This body weight gain was primarily due to increased body fat content. Average
      daily food intake tended to be higher in beacon-treated Psammomys obesus, but no
      effect of beacon administration on substrate oxidation, activity or energy
      expenditure was detected. CONCLUSION: The effects of beacon on body weight are
      due to increased food intake, with no detectable effect on nutrient partitioning,
      physical activity or energy expenditure.

PMID- 11571589
TI  - Acute effects of brain-derived neurotrophic factor on energy expenditure in obese
      diabetic mice.
AB  - OBJECTIVE: We recently demonstrated that chronic treatment with brain-derived
      neurotrophic factor (BDNF) regulates energy expenditure in obese diabetic
      C57BL/KsJ-db/db mice. In this study, we investigated the acute effects of BDNF on
      energy expenditure. DESIGN: After BDNF was singly administered to male db/db mice
      (aged 10-12 weeks), their body temperature and whole body glucose oxidation were
      measured. Their norepinephrine (NE) turnover and uncoupling protein (UCP) 1
      expression in interscapular brown adipose tissue (BAT) were also analyzed.
      RESULTS: Even though the body temperatures of hyperphagic db/db mice dropped
      remarkably in a 24 h period after food deprivation, only a single subcutaneous
      administration of BDNF significantly prevented the reduction of body temperature.
      BDNF was also observed to have similar efficacy in cold exposure experiments at
      15 degrees C. Respiratory excretion of (14)CO(2) after intravenous injection of D
      [(14)C(U)]-glucose was significantly increased by BDNF administration, indicating
      that BDNF increases whole-body glucose oxidation. BDNF administered
      intracerebroventricularly was also able to prevent the reduction of body
      temperature of db/db mice. To clarify the BDNF action mechanism we examined NE
      turnover in BAT. Four hours after a single administration, BDNF reduced NE
      content in the presence of the tyrosine hydroxylase inhibitor, alpha-methyl-P
      tyrosine methyl ester, indicating enhanced NE turnover in BAT. BDNF also
      increased the expression of the UCP1 mRNA and protein in BAT. CONCLUSION: These
      data indicate that BDNF rapidly regulates energy metabolism in obese diabetic
      animals, partly through activating the sympathetic nervous system and inducing
      UCP1 gene expression in BAT.

PMID- 11571590
TI  - The effect on adipose tissue blood flow of isoenergetic meals containing
      different amounts and types of fat.
AB  - OBJECTIVE: To investigate the factors regulating the increase in adipose tissue
      blood flow following meals. DESIGN: Eight subjects were fed three isoenergetic
      meals; two high-fat meals rich in either saturated or polyunsaturated fatty acids
      and one low-fat, high-carbohydrate meal. MEASUREMENTS: Blood samples were taken
      and adipose tissue blood flow was measured before and for 6 h after the meal.
      Plasma glucose, insulin, non-esterified fatty acid, total and chylomicron
      triacylglycerol and catecholamine concentrations were measured. RESULTS: Adipose
      tissue blood flow rose to a peak after all three meals (P<0.05 for each). The
      three meals stimulated adipose tissue blood flow at similar times. There was a
      marked and statistically significant similarity in the time course of changes in
      blood flow and insulin concentrations. In contrast, noradrenaline concentrations
      peaked later than adipose tissue blood flow (P=0.014). CONCLUSION: Adipose tissue
      blood flow may be 'carbohydrate-stimulated' rather than 'fat-stimulated', with
      insulin having a vasodilatory role in adipose tissue as in skeletal muscle.

PMID- 11571591
TI  - Skeletal muscle energetics assessed by (31)P-NMR in prepubertal girls with a
      familial predisposition to obesity.
AB  - OBJECTIVE: To determine whether skeletal muscle energetics, measured by in vivo
      (31)P-nuclear magnetic resonance spectroscopy during plantar flexion exercise,
      differ between multiethnic, prepubertal girls with or without a predisposition to
      obesity. DESIGN: Cross-sectional study. SUBJECTS: Girls (mean age and body fat+/
      s.d.=8.6+/-0.3 y and 22.6+/-4.2%) were recruited according to parental leanness
      or obesity defined as follows: LN (n=22), two lean parents, LNOB (n=18), one lean
      and one obese parent; and OB (n=15), two obese parents. MEASUREMENTS: A 3 min,
      rest-exercise-recovery plantar flexion protocol was completed. Work was
      calculated from the force data. Spectra were analyzed for inorganic intracellular
      phosphate (P(i)), phosphocreatine (PCr), P(i)/PCr (ratio of the low and high
      energy phosphates indicating the bioenergetic state of the cell), intracellular
      pH, and adenosine triphosphate (ATP). Magnetic resonance imaging was used to
      determine calf muscle volume. RESULTS: BMI was lower in the girls in the LN group
      (15.9+/-1.5 kg/m(2)) compared to the OB group (16.7+/-1.3 kg/m(2)) of girls
      (P<0.05), with no difference with the LNOB group (16.7+/-1.9 kg/m(2)). Adjusted
      for muscle volume and cumulative work, no differences in P(i), PCr, P(i)/PCr, pH,
      or ATP were observed among the LN, LNOB and OB groups at rest, the end of
      exercise, and after 60 and 300 s of recovery. From rest to the end of exercise,
      P(i) and P(i)/PCr (mean+/-s.d.: 0.2+/-0.1 vs 1.5+/-1.0) increased, whereas PCr
      and pH (7.04+/-0.06 vs 6.95+/-0.10) decreased (all P<0.001). By 60 s of recovery,
      P(i) and P(i)/PCr decreased, whereas PCr and pH increased (all P<0.001).
      CONCLUSIONS: Skeletal muscle energetics, specifically P(i)/PCr and pH measured
      during plantar flexion exercise, do not differ between prepubertal girls with or
      without a familial predisposition to obesity.

PMID- 11571592
TI  - Skeletal muscle metabolism in overweight and post-overweight women: an isometric
      exercise study using (31)P magnetic resonance spectroscopy.
AB  - OBJECTIVE: To investigate whether skeletal muscle anaerobic metabolism, oxidative
      metabolism or metabolic economy during controlled sub-maximal and near-maximal
      exercises is altered in overweight women after diet-induced weight reduction, and
      whether these parameters are different between normal-weight, obesity-prone and
      normal-weight obesity-resistant women with similar physical fitness levels.
      DESIGN: A prospective weight loss study of overweight women and their comparison
      with never overweight controls. SUBJECTS: Thirty overweight, nondiabetic,
      premenopausal women and 28 never overweight controls were included in this
      analysis. All were participating in a longitudinal investigation of the role of
      energy metabolism in the etiology of obesity. The overweight women were recruited
      specifically to have a positive family history of obesity and have a body mass
      index (BMI) between 27 and 30 kg/m(2) and were studied in the overweight state
      and after reduction to a normal weight. The never-overweight controls were
      recruited specifically to have no personal and family history of obesity and were
      group matched with the weight-reduced post-overweight subjects in terms of
      premenopausal status, age, BMI, race and sedentary lifestyle. MEASUREMENTS: All
      testing was performed following one month of weight maintenance and during the
      follicular phase of the menstrual cycle. Hydrostatic weighing was performed to
      measure body composition and a whole-body maximal oxygen uptake (VO(2max)) test
      was done to measure aerobic fitness. (31)P MRS was used to determine ATP
      production from oxidative phosphorylation (OxPhos), 'anaerobic' glycolysis
      (AnGly), and creatine kinase (CK), as well as muscle metabolic economy. The time
      constant of ADP (TC(ADP)), V(PCr) (ie the initial rate of PCr resynthesis
      following exercise), and Q(max) (ie the apparent maximal oxidative ATP production
      rate) were also calculated as additional markers of mitochondrial function.
      RESULTS: Diet-induced weight loss did not have any effects on the anaerobic
      metabolism markers (AnGly and CK). The aerobic metabolism markers calculated from
      the initial recovery data (OxPhos and V(PCr)) were unaffected by diet-induced
      weight loss. However, diet-induced weight loss resulted in improvements in the
      TC(ADP) and Q(max) in the post-overweight state as compared to their overweight
      state. There were no differences in any of the anaerobic (AnGly and CK) or
      oxidative metabolism markers (OxPhos, V(PCr), Q(max) and TC(ADP)) between the
      post-overweight and control groups. CONCLUSIONS: Once the overweight women were
      reduced to a normal-weight state, their skeletal muscle energy metabolism and
      economy was similar to the never overweight control women. In overweight women,
      oxidative metabolism or mitochondrial function may be limited by blood flow to
      the muscle following the cessation of exercise.

PMID- 11571593
TI  - Fat content in individual muscle fibers of lean and obese subjects.
AB  - OBJECTIVE: To examine skeletal muscle intracellular triglyceride concentration in
      different fiber types in relation to obesity. DESIGN: Skeletal muscle fiber type
      distribution and intracellular lipid content were measured in vastus lateralis
      samples obtained by needle biopsy from lean and obese individuals. SUBJECTS:
      Seven lean controls (body mass index (BMI) 23.0+/-3.3 kg/m(2); mean+/-s.d.) and
      14 obese (BMI 33.7+/-2.7 kg/m(2)) individuals; both groups included comparable
      proportions of men and women. MEASUREMENTS: Samples were histochemically stained
      for the identification of muscle fiber types (myosin ATPase) and intracellular
      lipid aggregates (oil red O dye). The number and size of fat aggregates as well
      as their concentration within type I, IIA and IIB muscle fiber types were
      measured. The cellular distribution of the lipid aggregates was also examined.
      RESULTS: The size of fat aggregates was not affected by obesity but the number of
      lipid droplets within muscle fibers was twice as abundant in obese compared to
      lean individuals. This was seen in type I (298+/-135 vs 129+/-75; obese vs lean,
      P<0.05), IIA (132+/-67 vs 79+/-29; P<0.05), and IIB (103+/-63 vs 51+/-13; P<0.05)
      muscle fibers. A more central distribution of lipid droplets was observed in
      muscle fibers of obese compared to lean subjects (27.2+/-5.7 vs 19.7+/-6.4%;
      P<0.05). CONCLUSION: The higher number of lipid aggregates and the disposition to
      a greater central distribution in all fiber types in obesity indicate important
      changes in lipid metabolism and/or storage that are fiber type-independent.

PMID- 11571594
TI  - Weight gain and adipose tissue metabolism after smoking cessation in women.
AB  - BACKGROUND: Cigarette smoking increases the risk of cardiovascular disease, and
      is an important preventable cause of death and illness. One major deterrent to
      smoking cessation is a gain in body weight. Understanding the mechanisms that
      contribute to this weight gain may maximize the success of long-term smoking
      cessation. We hypothesized that smoking cessation is associated with an increase
      in adipose tissue lipoprotein lipase (AT-LPL) activity and/or a decrease in
      lipolysis, two metabolic factors that determine the balance between fat storage
      and fat utilization, and thus affect the propensity for weight gain. MATERIALS
      AND METHODS: Ten premenopausal women (37.1+/-6.2 y, 31.7+/-6.4 kg/m(2) body mass
      index (BMI), mean+/-s.d.) participated in a 4 week smoking cessation program.
      Measurements of body weight, waist and hip circumferences, adipose cell
      metabolism and resting metabolic rate were obtained at baseline and after 4 weeks
      of smoking cessation. RESULTS: Of the 10 women who began the intervention, five
      successfully completed the smoking cessation intervention. After 4 weeks of
      smoking cessation, there were significant increases in body weight (95.1+/-13.9
      97.7+/-14.4 kg, P<0.05), with no change in waist and hip circumferences or
      resting energy expenditure. Gluteal AT-LPL activity significantly increased in
      all women by 2.8-fold (1.65+/-1.30-4.72+/-3.34 nmol/g/min, P<0.05). Abdominal AT
      LPL activity increased in four out of the five women, but did not reach
      statistical significance (1.14+/-0.88-3.50+/-3.76 nmol/g/min, P=0.14). The
      increase in body weight correlated with the increase in gluteal AT-LPL activity
      (r=0.89, P<0.05), as well as the baseline activity of gluteal AT-LPL (r=0.86,
      P=0.06). There were no changes in basal or stimulated lipolysis in the gluteal or
      abdominal fat depots. CONCLUSIONS: These results suggest that smoking cessation
      is associated with significant increases in body weight, as well as changes in
      adipose cell metabolism, in particular increases in AT-LPL activity. This
      increase in LPL activity may contribute to the increase in body weight associated
      with smoking cessation.

PMID- 11571595
TI  - Relation of C-reactive protein to body fat distribution and features of the
      metabolic syndrome in Europeans and South Asians.
AB  - OBJECTIVE: To investigate the association between circulating C-reactive protein
      (CRP) concentrations and indices of body fat distribution and the insulin
      resistance syndrome in South Asians and Europeans. DESIGN: : Cross-sectional
      study. SUBJECTS: A total of 113 healthy South Asian and European men and women in
      West London (age 40-55 y, body mass index (BMI) 17-34 kg/m(2)). MEASUREMENTS:
      Fatness and fat distribution parameters (by anthropometry, dual-energy X-ray
      absorptiometry and abdominal CT scan); oral glucose tolerance test with insulin
      response; modified fat tolerance test; and CRP concentration by sensitive ELISA.
      RESULTS: Median CRP level in South Asian women was nearly double that in European
      women (1.35 vs 0.70 mg/1, P=0.05). Measures of obesity and CRP concentration were
      significantly associated in both ethnic groups. The correlation to CRP was
      especially strong among South Asians (P<0.01) for measures of central obesity
      (waist girth and visceral fat area), whereas BMI and percentage fat were more
      significantly associated with CRP in Europeans (P<0.05). In South Asians the
      associations of CRP with visceral fat area and waist girth persisted after
      adjustment for either BMI or percent fat (all, P<0.05). In age-, sex- and smoking
      adjusted regression analyses CRP concentrations were significantly associated
      with fasting and 2 h insulin and lipid levels in both ethnic groups (P<0.05).
      When further statistical adjustment was made for visceral fat area these
      associations were abolished (P>0.15). CONCLUSION: We suggest that adiposity and
      in particular visceral adipose tissue is a key promoter of low-grade chronic
      inflammation. This observation may in part account for the association of CRP
      with markers of the metabolic syndrome. Future studies should confirm whether CRP
      concentrations are elevated in South Asians and whether losing weight by exercise
      or diet, or reduction in visceral fat mass, is associated with reduction in
      plasma CRP concentrations.

PMID- 11571596
TI  - Interactions among the glucocorticoid receptor, lipoprotein lipase and adrenergic
      receptor genes and abdominal fat in the Quebec Family Study.
AB  - OBJECTIVE: To investigate whether interactions between glucocorticoid receptor
      (GRL), lipoprotein lipase (LPL) and adrenergic receptor (ADR) gene markers
      contribute to individual differences in indicators of adiposity and abdominal
      obesity, including visceral fat level. DESIGN AND SUBJECTS: Cross-sectional
      study; 742 individuals from the phase 2 of the Quebec Family Study cohort.
      MEASUREMENTS: Total body fat assessed by hydrodensitometry and the sum of six
      skinfolds. Abdominal fat areas measured by computed tomography and adjusted for
      age, sex and total fat mass in all analyses. GRL Bcl I, alpha 2A-ADR Dra I and
      beta 2-ADR Ban I markers were typed by Southern blot, and other markers by
      polymerase chain reaction technique. RESULTS: It is confirmed that the 4.5 kb
      allele of the GRL BclI polymorphism is associated with a higher amount of
      abdominal visceral fat (AVF) depot (P for trend<0.001) independent of the level
      of total body fat. Furthermore, the alpha 2-ADR Dra I variant is associated with
      lower cross-sectional areas of abdominal total (P=0.003) and subcutaneous
      (P=0.012) adipose tissue. Gene-gene interactions between GRL and alpha 2-ADR
      genes affecting overall adiposity (P=0.016) as well as between GRL and beta 2-ADR
      genes (P=0.049) having influence on total abdominal fat levels were observed.
      When the three genes were considered together in the same analysis, significant
      interactions having influence on overall adiposity (P=0.017), abdominal total
      (P=0.032) and visceral fat (P=0.002) were observed. About 1-2% of the total
      variation in total fatness and abdominal fat was explained by these gene-gene
      interactions. CONCLUSION: There is an association between the GRL BclI
      polymorphism and increased AVF levels independent of the level of total body fat.
      The alpha 2-ADR DraI variant is associated with a lower cross-sectional area of
      abdominal total fat. Numerous interactions between GRL and ADR markers on overall
      adiposity and total abdominal fat as well as between GRL, LPL and ADR genes on
      overall adiposity, abdominal total and visceral fat suggest that the genetic
      architecture of body fat content and adipose tissue distribution is complex
      although some genes, like GRL, may have ubiquitous effects.

PMID- 11571597
TI  - Skinfold caliper and ultrasound assessments of change in the distribution of
      subcutaneous fat during adolescent pregnancy.
AB  - OBJECTIVE: This study compares skinfold caliper and sonographic measurements of
      the amount and distribution of subcutaneous adipose tissue teenagers gain during
      pregnancy to test three hypotheses: (1) skinfold caliper and sonographic
      measurements of subcutaneous adiposity are highly correlated in pregnancy; (2)
      the extent to which the skinfold caliper heads compact the tissues increases
      during gestation; and (3) skinfold caliper measurements yield a smaller estimate
      of the amount of subcutaneous adipose tissue gained during gestation than do
      sonographic measurements. METHODS: We studied 28 primiparous teenagers at 10.7+/
      2.8 and 29.6+/-1.8 weeks gestation. At both study visits subcutaneous adipose
      tissue thickness was measured at six body sites, first by skinfold caliper and
      then by ultrasound. Taking the nearly compression-free sonographic measurements
      as the standard, we quantified the extent to which the skinfold caliper heads
      compacted the tissues at each measurement site by computing the percentage
      compression: (mean adipose tissue thickness by ultrasound-(0.5xmean adipose
      tissue thickness by caliper)/mean adipose tissue thickness by ultrasound)x100.
      Pearson correlations and paired t-tests were used to compare the skinfold caliper
      and sonographic measurements. RESULTS: Hypothesis 1 was supported; the skinfold
      caliper and sonographic measurements were highly correlated at both study visits.
      Hypothesis 2 was not supported; between study visits caliper-related tissue
      compression decreased at measurement sites on the trunk and remained the same at
      measurement sites on the extremities. Hypothesis 3 was also refuted; the skinfold
      caliper-derived estimate of the amount of subcutaneous adipose tissue gained on
      the trunk exceeded the corresponding sonographic determination. As anticipated,
      the skinfold caliper measurements indicated that adipose tissue was stored more
      rapidly on the trunk than the extremities, but the opposite pattern emerged when
      the sonographic measurement technique was used. CONCLUSIONS: The results of this
      study challenge the notion that pregnant women store adipose tissue
      preferentially on the trunk and suggest that pregnancy-related changes in the
      regional distribution of maternal body fat based on skinfold caliper measurements
      should be interpreted cautiously.

PMID- 11571598
TI  - Validity and reproducibility of ultrasonography for the measurement of intra
      abdominal adipose tissue.
AB  - OBJECTIVE: We studied the validity and reproducibility of a new abdominal
      ultrasound protocol for the assessment of intra-abdominal adipose tissue.
      MEASUREMENTS: Intra-abdominal adipose tissue was assessed by CT, MRI,
      anthropometry and ultrasonography on a single day. By ultrasonography the
      distance between peritoneum and lumbar spine was measured using a strict
      protocol, including the location of the measurements, pressure on the transducer
      and respiration. All measurements were repeated after 3 months. RESULTS: The
      study population consisted of 19 overweight patients with a body mass index (BMI)
      of 32.9 kg/m(2) (s.d. 3.7), intra-abdominal adipose tissue on CT 140.1 cm(2)
      (s.d. 55.9), and a mean ultrasound distance of 9.8 cm (s.d. 2.5). There was a
      strong association between the CT and ultrasonographic measures: Pearson
      correlation coefficient was 0.81 (P<0.001). The correlation between ultrasound
      and waist circumference was 0.74 (P<0.001), the correlation between CT and waist
      circumference was 0.57 (P=0.01). Ultrasound appeared a good method to diagnose
      intra-abdominal obesity: the area under the ROC curve was 0.98. During the follow
      up period of 3 months, the patients lost on average almost 3 kg of body weight.
      The correlation coefficient between changes in intra-abdominal adipose tissue
      assessed by CT and ultrasound was 0.74 (P<0.001). The correlation coefficient of
      the mean ultrasound distance assessed by two different sonographers at baseline
      was 0.94 (P<0.001), the mean difference 0.4 cm (s.d. 0.9), and the coefficient of
      variation 5.4%, indicating good reproducibility of the ultrasound measurements.
      CONCLUSIONS: The results of this validation study show that abdominal ultrasound,
      using a strict protocol, is a reliable and reproducible method to assess the
      amount of intra-abdominal adipose tissue and to diagnose intra-abdominal obesity.

PMID- 11571599
TI  - Body composition in prepubertal girls: comparison of six methods.
AB  - OBJECTIVE: To compare estimates of fat mass (FM), fat-free mass (FFM) and
      percentage body fat (%fat) by six different methods in prepubertal girls. DESIGN:
      Cross-sectional study. SUBJECTS: Normal-weight, multi-ethnic, prepubertal girls
      (age=8.5+/-0.4 y, n=101). MEASUREMENTS: Body composition was measured in each
      child by anthropometry (skinfold thickness using Slaughter equation), dual-energy
      X-ray absorptiometry (DXA), total body potassium (TBK), isotope dilution for
      total body water measurement (TBW), multifrequency bioelectrical impedance
      spectroscopy (BIS), and total body electrical conductivity (TOBEC). RESULTS:
      TOBEC and skinfold thickness yielded the lowest values of FM followed by DXA,
      TBK, TBW and BIS, with BIS giving the highest value of FM. All methods were
      significantly different for FFM, FM and %fat (P<0.001), except FFM by DXA and
      TBK. The Bland-Altman limits of agreement among the methods reveal that they are
      not directly interchangeable for FM, FFM, or %fat. The largest mean difference
      for FM was between TOBEC and BIS (-2.90 kg), whereas the smallest mean difference
      was between TOBEC and skinfold thickness (-0.14 kg). For FFM, the largest mean
      difference was also between TOBEC and BIS (2.83 kg), but the smallest mean
      difference for FFM was between DXA and TBK (-0.03 kg). For %fat, the mean
      differences were larger, -10.5% for TOBEC and BIS and+9.7% for skinfold thickness
      and BIS. The closest two techniques for %fat were TOBEC and skinfold thickness
      (mean difference of -0.62%) and DXA and TBK (-1.81%). CONCLUSIONS: We found that
      estimates of body composition in prepubertal 8-y-old girls are highly method
      dependent and that the six methods studied (DXA, TBK, TBW, TOBEC, BIS and
      anthropometry) are not directly interchangeable.

PMID- 11571600
TI  - Large waist circumference and risk of hypertension.
AB  - OBJECTIVE: To examine the relationship between 24 h ambulatory blood pressure
      monitoring and three commonest anthropometric measurements for obesity--body mass
      index (BMI), waist-to-hip ratio (WHR) and waist circumference (W). DESIGN: Cross
      sectional survey among outpatients at the Obesity Research Center. SUBJECTS AND
      METHODS: Four-hundred and sixty-one overweight or obese subjects, non-diabetic,
      otherwise healthy, aged 20-70 y, of either sex, were consecutively recruited. All
      subjects underwent 24 h ambulatory blood pressure monitoring. The population
      study was separated in normotensive and hypertensive males and females and the
      possible risk factors for hypertension (W, WHR, BMI and age) were subdivided into
      different classes of values. RESULTS: Logistic regression shows that W is the
      most important anthropometric factor associated with the hypertensive risk. Among
      males with W> or =102 cm the odds ratio (OR) for hypertension is three times that
      of males with W<94 cm using casual BP measure (OR 3.04), nearly four times higher
      using 24 h BP mean (OR 3.97), and even five times higher using day-time BP mean
      (OR 5.19). Females with W> or =88 cm have a risk for hypertension twice that of
      females with W<80 cm, whatever BP measurement was take (casual, 24 h or day
      time). Males with WHR> or =0.96 and females with WHR> or =0.86 show significant
      OR for hypertension only by 24 h BP measurement and by day-time BP measurement.
      BMI seems to have no significant relationship to hypertensive risk. Age shows a
      significant relationship to hypertensive risk only considering males aged > or
      =55 y and females aged > or =50 y. CONCLUSION: The waist circumference seems to
      have a strong association with the risk of hypertension, principally by the
      ambulatory BP monitoring, when compared with casual BP measurement.

PMID- 11571601
TI  - Sexual dimorphism in circulating leptin concentrations is not accounted for by
      differences in adipose tissue distribution.
AB  - BACKGROUND: Circulating concentrations of leptin normalized to total adipose
      tissue mass are significantly greater in females than in males. Rates of leptin
      expression (per gram of adipose tissue) are significantly greater in subcutaneous
      (SAT) than visceral (VAT) adipose tissue and the relative amount of fat stored as
      SAT vs VAT is significantly greater in pre-menopausal females than in males.
      Gender-related differences in the relative amounts of SAT and VAT may account for
      the greater circulating leptin concentration relative to fat-mass in females than
      males. METHODS: We examined body composition and anatomic fat distribution by
      dual energy X-ray-absorptiometry (DEXA) and magnetic resonance imaging (MRI), and
      post-absorptive circulating concentrations of leptin and insulin in 58 subjects
      (26 females, 32 males). Stepwise multiple linear regression analyses, treating
      gender as a dichotomous variable, were performed to determine inter-relationships
      among leptin concentrations and insulin concentrations, VAT and SAT. RESULTS:
      Body composition by DEXA and MRI were highly correlated (r(2)=0.97, P<0.0001).
      There were significant gender effects on leptin/total fat mass (males, 0.17+/
      0.01 ng/ml/kg; females, 0.49+/-0.05 ng/ml/kg; P<0.0001) and relative amounts of
      fat in SAT and VAT depots (ratio of SAT/VAT; males, 12.3+/-1.5; females, 32.9+/
      3.2; P<0.0001). Circulating leptin concentration was significantly correlated
      with insulin concentration (P=0.001), SAT (P<0.0001) and gender (P=0.033).
      Circulating concentrations of insulin were significantly correlated with VAT, but
      not SAT, in males and with SAT, but not VAT, in females. CONCLUSIONS: The sexual
      dimorphism in the relationship between leptin and adipose tissue mass cannot be
      explained by differences in the relative amounts of VAT and SAT. Thus, the sexual
      dimorphism in plasma leptin concentration appears to reflect, at least in part,
      effects of circulating concentrations of gonadal steroids (especially androgens)
      and/or primary genetic differences that are independent of amounts of VAT or SAT.

PMID- 11571602
TI  - Extremely high prevalence of overweight and obesity in Murcia, a Mediterranean
      region in south-east Spain.
AB  - OBJECTIVE: To estimate the prevalence of obesity in the Murcia Region according
      to age and sex, and to analyse how obesity is related to demographic and socio
      economic determinants and to other cardiovascular risk factors of interest to the
      community. DESIGN: Survey on a representative population sample using multi-stage
      random sampling with definition of the sample quotas. SUBJECTS: A total of 3091
      persons aged 18-65 y residing in the Murcia Region. MEASUREMENTS: : The following
      data were collected: socio-economic data; tobacco smoking; recent physical
      activity; blood pressure; weight; height; and blood analysis to determine plasma
      lipids. Obesity was defined by body mass index (BMI)> or =30. Intense or vigorous
      physical activity (VPA> or =6 equivalents to baseline metabolic rate or METs) was
      measured in kilocalories per day and reduced to hours per week. RESULTS: In all,
      20.5% of the adult population of the Murcia Region is obese, and 40.9% is
      overweight. In the logistic regression analysis, obesity in men is associated
      with age and level of education. In women it is associated with age, level of
      education, living in a non-urban area and being a housewife. When adjusted for
      socio-economic variables and for other cardiovascular risk factors the effect of
      age and level of education disappears in men and it is directly associated with
      hypertension and hypertriglyceridaemia and inversely related to more than 2 h VPA
      per week. Obesity in women is associated positively with age, hypertension,
      hypertriglyceridaemia and little VPA, and inversely with level of education.
      CONCLUSIONS: In the Murcia Region 61.4% of the adult population presents with
      some form of excess weight. The prevalence of obesity (BMI> or =30) is greater in
      women (23.7%; CI 95% 19.7-27.7) than in men (17.3%; CI 95% 15.3-19.3). The
      widespread nature of this factor makes it a mass problem that requires
      generalised interventions to prevent it.

PMID- 11571603
TI  - Smoking and weight loss attempts in overweight and normal-weight adolescents.
AB  - AIM: To explore the relationship between smoking and dieting in a cross-sectional
      nationally representative sample of young adolescents. METHODS: Smoking was
      assessed by serum cotinine concentrations in 1132 adolescents aged 12-18 y
      enrolled in the NHANES III study. Information on adolescents' weight loss
      attempts were obtained by questionnaire. Normal weight was defined as a body mass
      index (BMI) less than the 85th percentile for age and gender. Overweight was
      defined as a BMI equal to or greater than the 85th percentile for age and gender.
      Nutritional intake was assessed with a 24 h recall and food frequency
      questionnaire. RESULTS: There was a two-fold increase in smoking among normal
      weight adolescent girls who reported trying to lose weight (23.7% vs 12.6%,
      P<0.01). In contrast, prevalence of smoking was similar among overweight
      adolescent girls who tried to lose weight compared to those who did not (15.8% vs
      14.1%, P=0.76). Similar trends were observed in boys. However, overweight boys
      who were trying to lose weight were less likely to smoke than overweight boys who
      were not trying to lose weight (9.8% vs 24.5%, P<0.05). There were no differences
      in body weight, BMI, caloric intake or fat intake among smokers and non-smokers.
      However, smokers reported eating less fruit and vegetables compared to non
      smokers, and were over five times more likely to drink alcohol compared to non
      smokers (odds ratio: > or =1x/month, 5.28 (3.82-7.28), > or =4x/month, 5.29 (3.58
      7.82). CONCLUSION: Tobacco use is common among normal weight adolescents trying
      to lose weight. Tobacco use is also associated with a cluster of other unhealthy
      dietary practices in adolescents.

PMID- 11571604
TI  - The relationship between quality of life and perceived body weight and dieting
      history in Dutch men and women.
AB  - OBJECTIVES: (1) To study the relationship between quality of life (QoL) and
      measured and perceived weight and dieting history in Dutch men and women; (2) to
      assess the effect of weight loss over a 5 y period on QoL. DESIGN: A cross
      sectional study, in a sub-sample longitudinal over 5 y. SUBJECTS: A total of 2155
      men and 2446 women, aged 20-59 and recruited from the general population from
      three towns in The Netherlands. MEASUREMENTS: Body weight, height, self
      administered questionnaire including questions concerning demographic variables
      and weight loss practices as part of the Dutch Monitoring project on Risk Factors
      for Chronic Disease (MORGEN). The Rand-36 questionnaire was used as the QoL
      measure. RESULTS: In men, measured overweight (body mass index, BMI>25 kg/m(2))
      was not associated with any dimension of QoL after adjustment for age,
      educational level and perceived overweight. Perceived overweight was related to
      reduced scores for general health and vitality. This relationship was independent
      of measured obesity. A history of repeated weight loss was associated with
      reduced scores for role functioning due to both physical and emotional problems.
      In women, measured overweight was significantly associated with lower scores for
      five out of eight QoL dimensions and perceived overweight with three: general
      health, vitality and physical functioning. A history of frequent weight loss was
      related to significantly reduced scores in six dimensions. However, only with
      history of frequent weight loss, and uniquely in women, was there a significant
      reduction in scores on mental health and limited emotional role functioning.
      Measured and perceived overweight and frequent weight loss were all related to
      reduced scores for physical functioning. Longitudinal data indicate that in older
      women weight gain of 10% body weight or more was associated with a significant
      deterioration in QoL. CONCLUSIONS: When looking at measures of QoL in relation to
      overweight it is important to separate the effects of perception of weight status
      and history of weight loss. We observed that the latter two factors were
      associated with reduced scores on several dimensions of QoL, particularly in
      women. These associations were observed to be independent of body weight.

PMID- 11571605
TI  - Value of VLCD supplementation with medium chain triglycerides.
AB  - BACKGROUND: Medium chain triglycerides (MCT) are energetically less dense, highly
      ketogenic, and more easily oxidised than long chain triglycerides (LCT). MCT also
      differ from LCT in their digestive and metabolic pathways. OBJECTIVE: To test the
      effects of MCT supplementation during a very low calorie diet (VLCD). SUBJECTS
      AND METHODS: Three groups of tightly matched obese women with body mass index
      (BMI)>30 kg/m(2) received an isoenergetic (578.5 kcal) VLCD (Adinax, Novo Vital,
      Sweden) enriched with MCT or LCT (8.0 and 9.9 g/100 g Adinax respectively) or a
      low-fat (3 g/100 g) and high-carbohydrate regimen. The diets were administered
      over 4 weeks. Body composition was measured with DEXA and appetite/satiety
      according to Blundell. Beta hydroxybutyric acid concentration in plasma and
      nitrogen excretion in urine was measured during consecutive days of VLCD. The
      study was performed in a randomised double-blind manner. RESULTS: The MCT group
      showed a significantly greater decrease in body weight during the first 2 weeks.
      The contribution of body fat to the total weight loss was higher while the
      contribution of fat-free mass (FFM) was lower. The MCT group had a higher
      concentration of ketone bodies in plasma and a lower nitrogen excretion in urine.
      Hunger feelings were less intense while satiety was higher. These differences
      were observed during the first 2 weeks of treatment and gradually declined during
      the third and fourth weeks. CONCLUSIONS: Replacement of LCT by MCT in the VLCD
      increased the rate of decrease of body fat and body weight and has a sparing
      effect on FFM. The intensity of hunger feelings was lower and paralleled the
      higher increase of ketone bodies. These effects gradually declined, indicating
      subsequent metabolic adaptation. Further studies are required to confirm the
      protein-sparing and appetite-suppressing effects of MCT supplementation during
      the first 2 weeks of VLCD treatment.

PMID- 11571606
TI  - Analyzing exposure of school children to accidental releases of hazardous
      substances.
AB  - Concerns regarding consequences of hazardous chemical accidents and children's
      environmental health have increased substantially in recent years. The objectives
      of this paper are to: (a) demonstrate a methodology for identifying areas
      potentially exposed to accidental releases of hazardous substances in a large
      metropolitan region (Hillsborough County, Florida); (b) examine the number and
      type of schools and school children at risk; and (c) explore the relationship
      between potential exposure levels and school enrollment patterns in the region.
      Methods based on the integration of environmental modeling and geographic
      information systems (GIS) technology are used to achieve these goals. The results
      indicate that almost 80% of schools and enrolled students in the study area is
      potentially exposed to worst-case accidents. Compared to elementary school
      children, a higher proportion of middle school children and a lower proportion of
      high school students are exposed to multiple releases of hazardous chemicals. A
      significant and negative association is observed between exposure levels and
      school enrollment size, which suggests fewer children in regions of highest
      exposure.

PMID- 11571608
TI  - Epidemiological studies of acute ozone exposures and mortality.
AB  - Many, but not all, observational epidemiological studies of ozone (O(3)) air
      pollution have yielded significant associations between variations in daily
      ambient concentrations of this pollutant and a wide range of adverse health
      outcomes. We evaluate some past epidemiological studies that have assessed the
      short-term association of O(3) with mortality, and investigate one possible
      reason for variations in their O(3) effect estimate, i.e., differences in their
      approaches to the modeling of weather influences on mortality. For all of the
      total mortality-air pollution time-series studies considered, the combined
      analysis yielded a relative risk, RR=1.036 per 100-ppb increase in daily 1-h
      maximum O(3) (95% CI: 1.023-1.050). However, the subset of studies that specified
      the nonlinear nature of the temperature-mortality association yielded a combined
      estimate of RR=1.056 per 100 ppb (95% CI: 1.032-1.081). This indicates that past
      time-series studies using linear temperature-mortality specifications have
      underpredicted the premature mortality effects of O(3) air pollution. For
      Detroit, MI, an illustrative analysis of daily total mortality during 1985-1990
      also indicated that the model weather specification choice can influence the O(3)
      health effects estimate. Results were intercompared for alternative weather
      specifications. Nonlinear specifications of temperature and relative humidity
      (RH) yielded lower intercorrelations with the O(3) coefficient, and larger O(3)
      RR estimates, than a base model employing a simple linear spline of hot and cold
      temperature. We conclude that, unlike for particulate matter (PM) mass, the
      mortality effect estimates derived by time-series analyses for O(3) can be
      sensitive to the way that weather is addressed in the model. The same may well
      also be true for other pollutants with largely temperature-dependent formation
      mechanisms, such as secondary aerosols. Generally, we find that the O(3)
      mortality effect estimate increases in size and statistical significance when the
      nonlinearity and the humidity interaction of the temperature-health effect
      association are incorporated into the model weather specification. We recommend
      that a minimization of the intercorrelations of model coefficients be considered
      (along with other critical factors such as goodness of fit, autocorrelation, and
      overdispersion) when specifying such a model, especially when individual
      coefficients are to be interpreted for risk estimation.

PMID- 11571607
TI  - Dietary exposure to chlorpyrifos and levels of 3,5,6-trichloro-2-pyridinol in
      urine.
AB  - Information on associations between chlorpyrifos residues in food and personal
      exposure to chlorpyrifos would be valuable for evaluating the relationship
      between personal exposure and possible health effects. We used food consumption
      records, chlorpyrifos levels in duplicate plates, and measures of 3,5,6-trichloro
      2-pyridinol (TCPy) in urine obtained from human volunteers in the National Human
      Exposure Assessment Survey in Maryland (NHEXAS-MD) to evaluate a food consumption
      chemical residue model for estimating dietary intake of chlorpyrifos. Model
      inputs were the NHEXAS-MD food consumption records and chlorpyrifos residues in
      specific foods measured in the U.S. Food and Drug Administration Total Diet Study
      (TDS) market baskets from 1993 to 1997. The estimated mean and standard deviation
      of chlorpyrifos concentration (microg/kg) in duplicate plates (n=203) were within
      20% and 50%, respectively, of the corresponding parameters of measured
      chlorpyrifos levels. However, predicted and measured concentrations in the 78
      duplicate plates with detectable levels of chlorpyrifos were not significantly
      associated according to Spearman correlation analysis (r=0.04, p=0.7667) and
      linear regression (p=0.2726). Measured and estimated chlorpyrifos intakes for
      observations with non-zero values for each intake measure (n=71) were moderately
      associated on a rank (Spearman's r=0.24, p=0.0462) and linear basis (regression
      r(2)=0.07, p=0.0242). Measured intakes of chlorpyrifos from food and urinary TCPy
      were significantly correlated in rank order (n=87, Spearman's r=0.30, p=0.0041)
      and linear (n=87, Pearson's r=0.22, p=0.0409) analyses. Correlation coefficients
      between estimated intake of chlorpyrifos from food and TCPy were significantly
      different from zero (n=87; Spearman's r=0.22, p=0.0393; Pearson's r=0.21,
      p=0.0479). Comparing mean measured chlorpyrifos intake from food (0.46
      microg/day) to mean estimated TCPy excretion via urine (6.3 microg/day), dietary
      intake of chlorpyrifos accounted for approximately 7% of TCPy in this population.
      These findings suggest the food consumption-chemical residue model can yield
      reasonably accurate estimates of the population distribution of dietary
      chlorpyrifos intake, but has little ability to predict dietary exposure for
      individuals; and that intake of chlorpyrifos from food is a minor contributor to
      TCPy in urine.

PMID- 11571609
TI  - Source apportionment of exposure to toxic volatile organic compounds using
      positive matrix factorization.
AB  - Data from the Total Exposure Assessment Methodology studies, conducted from 1980
      to 1987 in New Jersey (NJ) and California (CA), and the 1990 California Indoor
      Exposure study were analyzed using positive matrix factorization, a receptor
      oriented source apportionment model. Personal exposure and outdoor concentrations
      of 14 and 17 toxic volatile organic compounds (VOCs) were studied from the NJ and
      CA data, respectively. Analyzing both the personal exposure and outdoor
      concentrations made it possible to compare toxic VOCs in outdoor air and exposure
      resulting from personal activities. Regression analyses of the measured
      concentrations versus the factor scores were performed to determine the relative
      contribution of each factor to total exposure concentrations. Activity patterns
      of the NJ and CA participants were examined to determine whether reported
      exposures to specific sources correspond to higher estimated contributions from
      the factor identified with that source. For a subset of VOCs, a preliminary
      analysis to determine irritancy-based contributions of factors to exposures was
      carried out. Major source types of toxic VOCs in both NJ and CA appear to be
      aromatic sources resembling automobile exhaust, gasoline vapor, or environmental
      tobacco smoke for personal exposures, and automobile exhaust or gasoline vapors
      for outdoor concentrations.

PMID- 11571610
TI  - Use of expert judgment in exposure assessment. Part I. Characterization of
      personal exposure to benzene.
AB  - This paper presents the results of the first phase of a study, conducted as an
      element of the National Human Exposure Assessment Survey (NHEXAS), to demonstrate
      the use of expert subjective judgment elicitation techniques to characterize the
      magnitude of and uncertainty in environmental exposure to benzene. In decisions
      about the value of exposure research or of regulatory controls, the
      characterization of uncertainty can play an influential role. Classical methods
      for characterizing uncertainty may be sufficient when adequate amounts of
      relevant data are available. Frequently, however, data are neither abundant nor
      directly relevant, making it necessary to rely to varying degrees on subjective
      judgment. Since the 1950s, methods to elicit and quantify subjective judgments
      have been explored but have rarely been applied to the field of environmental
      exposure assessment. In this phase of the project, seven experts in benzene
      exposure assessment were selected through a peer nomination process, participated
      in a 2-day workshop, and were interviewed individually to elicit their judgments
      about the distributions of residential ambient, residential indoor, and personal
      air benzene concentrations (6-day integrated average) experienced by both the non
      smoking, non-occupationally exposed target and study populations of the US EPA
      Region V pilot study. Specifically, each expert was asked to characterize, in
      probabilistic form, the arithmetic means and the 90th percentiles of these
      distributions. This paper presents the experts' judgments about the
      concentrations of benzene encountered by the target population. The experts'
      judgments about levels of benzene in personal air were demonstrative of patterns
      observed in the judgments about the other distributions. They were in closest
      agreement about their predictions of the mean; with one exception, their best
      estimates of the mean fell within 7-11 microg/m(3) although they exhibited
      striking differences in the degree of uncertainty expressed. Their estimates of
      the 90th percentile were more varied with the best estimates ranging from 12 to
      26 microg/m(3) for all but one expert. However, their predictions of the 90th
      percentile were far more uncertain. The paper demonstrates that coherent
      subjective judgments can be elicited from exposure assessment scientists and
      critically examines the challenges and potential benefits of a subjective
      judgment approach. The results of the second phase of the project, in which
      measurements from the NHEXAS field study in Region V are used to calibrate the
      experts' judgments about the benzene exposures in the study population, will be
      presented in a second paper.

PMID- 11571611
TI  - Measurement of bisphenol A levels in human urine.
AB  - We report a new approach for assessing human exposure to bisphenol A (BPA) by
      measuring BPA in urine after enzymatic deglucuronidation. This method involves
      addition of (13)C(12)-labeled BPA, enzymatic deconjugation, solid-phase
      extraction, and derivatization with pentafluorobenzyl bromide. The product of the
      derivatization is separated by gas chromatography followed by mass spectrometric
      detection using negative chemical ionization and selected ion monitoring. Using
      this analysis method, urine samples fortified with both a constant level of
      labeled BPA and a range of unlabeled BPA levels (0.27-10.6 ng/ml) demonstrated
      constant percentage recovery. In addition, a range of urine sample volumes (0.25
      10.0 ml) with constant amounts of added internal standard produced a linear
      response (r(2)=0.99). The method limit of detection was 0.12 ng/ml. This method
      was validated by duplicate analyses using gas chromatography coupled to a high
      resolution mass spectrometer.

PMID- 11571612
TI  - Locational uncertainty in georeferencing public health datasets.
AB  - The assignment of locational attributes to a study subject in epidemiologic
      analyses is commonly referred to as georeferencing. When georeferencing study
      subjects to a point location using their residential street address, most
      researchers rely on the street centerline data model. This study assessed the
      potential locational bias introduced using street centerline data. It also
      evaluated georeferencing effects on a location-dependent, exposure assessment
      process. For comparison purposes, subjects were georeferenced to the center of
      their residential parcel of land using digitized parcel maps. A total of 10,026
      study subjects residing in Jefferson County, Alabama were georeferenced using
      both street centerline and residential parcel methods. The mean nondirectional,
      linear distance between points georeferenced using both methods was 246 ft with a
      range of 11 to 13,260 ft. Correlation coefficients comparing differences in
      exposure estimates were generated for all 10,026 subjects. Coefficients increased
      as the geographic areas of analysis around study subjects increased, indicating
      the influence of nondifferential exposure misclassification.

PMID- 11571613
TI  - Acute health effects of organophosphorus pesticides on Tanzanian small-scale
      coffee growers.
AB  - Acute health effects of organophosphorus (OP) pesticides on coffee farmworkers in
      1991-1992 in Tanzania are reported to provide a basis for concern over
      farmworkers being overexposed during application. Workers exposed to OP
      pesticides (N=133) were drawn from a population of about 240,000 coffee farmers.
      They were interviewed on symptoms and personal protection, and their erythrocyte
      acetylcholinesterase (AChE) activity was determined during both spraying and
      nonspraying period. AChE activities during spraying and nonspraying period were
      comparable (mean 32.0, SD 7.8 vs. 33.0, SD 8.7 U/g HgB, P=0.26). The prevalence
      of cough, headache, abdominal pain, excessive sweating, nausea, excessive
      salivation, diarrhea, and vomiting did not differ significantly between spraying
      and nonspraying periods. There was no suggestion of decreased AChE in exposed
      subjects who complained of OP-related symptoms compared to symptomless exposed
      subjects. Use of gloves, long boots, head cover, face cover, and coverall was not
      significantly associated with AChE activity. No marked AChE depression was found
      during spraying season, which may explain the lack of association between
      symptoms and AChE. The fact that only moderately toxic OP pesticides were used
      may indicate that toxicity was not sufficiently high to cause depression.
      Experience, however, suggests that occupational poisoning remains a potential
      serious danger in coffee cultivation in Tanzania.

PMID- 11571614
TI  - beta-Carotene production in sugarcane molasses by a Rhodotorula glutinis mutant.
AB  - Several wild strains and mutants of Rhodotorula spp. were screened for growth,
      carotenoid production and the proportion of -carotene produced in sugarcane
      molasses. A better producer, Rhodotorula glutinis mutant 32, was optimized for
      carotenoid production with respect to total reducing sugar (TRS) concentration
      and pH. In shake flasks, when molasses was used as the sole nutrient medium with
      40 g l(-1) TRS, at pH 6, the carotenoid yield was 14 mg l(-1) and -carotene
      accounted for 70% of the total carotenoids. In a 14-l stirred tank fermenter, a
      20% increase in torulene content was observed in plain molasses medium. However,
      by addition of yeast extract, this effect was reversed and a 31% increase in 
      carotene content was observed. Dissolved oxygen (DO) stat fed-batch cultivation
      of mutant 32 in plain molasses medium yielded 71 and 185 mg l(-1) total
      carotenoids in double- and triple-strength medium, respectively. When
      supplemented with yeast extract, the yields were 97 and 183 mg l(-1) total
      carotenoid with a 30% increase in -carotene and a simultaneous 40% decrease in
      torulene proportion. Higher cell mass was also achieved by double- and triple
      strength fed-batch fermentation.

PMID- 11571615
TI  - Phosphate uptake and release by Acinetobacter johnsonii in continuous culture and
      coupling of phosphate release to heavy metal accumulation.
AB  - A strain of polyphosphate-synthesizing, phosphate-releasing Acinetobacter
      johnsonii was isolated from a wastewater treatment plant operating enhanced
      biological phosphate removal (EBPR) and was used to remove La(3+) from solution
      via precipitation of cell-bound LaPO(4). The effect of repeated aerobic-anaerobic
      cycles on the carbon and phosphate metabolism of the organism was studied in
      attempts to promote increased phosphate flux using a three-stage, continuous
      bioreactor comprising aerobic, anaerobic and settling vessels. The bioreactor was
      operated in two modes: In flow-through mode, cells were grown aerobically with
      acetate as the sole carbon source, promoting excess phosphate uptake (up to 5.0
      mmol/l=3.0 mmol/g protein). Cells were diluted into the anaerobic vessel where
      phosphate was released (up to 1.0 mmol/l=0.3 mmol/g protein), and thence to
      waste. The system was initially operated to steady state in flow-through mode,
      then switched to recycle mode. Here the anaerobic vessel output passed to a
      settling vessel from which settled cells were returned to the aerobic vessel.
      Carbon source (acetate) was supplied only to the anaerobic vessel; increased
      anaerobic acetate uptake was observed during recycle, which was sustained when
      the system was returned to flow-through mode and was related to increased
      cellular lipid inclusions by flow cytometry and electron microscopy. These
      phenomena may represent adaptation of cells to aerobic-anaerobic cycling with
      aerobic carbon/energy limitation. Addition of La(3+) to the anaerobic vessel
      during recycle mode promoted removal of 95% of the La(3+) from a 0.1 to 0.3 mM
      (14-42 ppm) solution at the expense of biogenic phosphate.

PMID- 11571616
TI  - Induction of microcin B17 formation in Escherichia coli ZK650 by limitation of
      oxygen and glucose is independent of glucose consumption rate.
AB  - We examined the consumption of glucose from the media in which Escherichia coli
      ZK650 was grown. This organism, which produces the polypeptide antibiotic
      microcin B17 best under conditions of limiting supplies of glucose and air, was
      grown with a low level of glucose (0.5 mg/ml) as well as a high level (5.0 mg/ml)
      under both high and low aeration. Glucose consumption rates were virtually
      identical under both high and low aeration. Thus, glucose consumption rate is not
      a regulating factor in microcin B17 formation.

PMID- 11571617
TI  - Detection of immunomagnetically captured Escherichia coli O157:H7 by antibody
      conjugated alkaline phosphatase.
AB  - A rapid and sensitive detection process for Escherichia coli O157:H7 was
      developed using alkaline phosphatase (APase)-labeled anti-E. coli O157 antibodies
      to tag the targeted bacteria. Immunomagnetic beads or antibody-labeled
      streptavidin-coated magnetic beads were then used to capture the APase-tagged E.
      coli. Immunomagnetically captured bacteria were washed and distributed into
      microplates or optical cuvettes. The enzyme-catalyzed hydrolysis of p-nitro
      phenol phosphate in alkaline solutions was then followed. Less than 1000 cfu/ml
      of E. coli O157:H7 could be detected. This approach was applied to detect the
      bacteria artificially spiked in beef hamburgers. Less than 1 cfu/g of E. coli
      O157:H7 produced a significant response after cultural enrichment for 4-6 h at 37
      degrees C.

PMID- 11571618
TI  - Control of biogenic H(2)S production with nitrite and molybdate.
AB  - The effects of the metabolic inhibitors, sodium nitrite and ammonium molybdate,
      on production of H(2)S by a pure culture of the sulfate-reducing bacterium (SRB)
      Desulfovibrio sp. strain Lac6 and a consortium of SRB, enriched from produced
      water of a Canadian oil field, were investigated. Addition of 0.1 mM nitrite or
      0.024 mM molybdate at the start of growth prevented the production of H(2)S by
      strain Lac6. With exponentially growing cultures, higher levels of inhibitors,
      0.25 mM nitrite or 0.095 mM molybdate, were required to suppress the production
      of H(2)S. Simultaneous addition of nitrite and molybdate had a synergistic
      effect: at time 0, 0.05 mM nitrite and 0.01 mM molybdate, whereas during the
      exponential phase, 0.1 mM nitrite and 0.047 mM molybdate were sufficient to stop
      H(2)S production. With an exponentially growing consortium of SRB, enriched from
      produced water of the Coleville oil field, much higher levels of inhibitors, 4 mM
      nitrite or 0.47 mM molybdate, were needed to stop the production of H(2)S. The
      addition of these inhibitors had no effect on the composition of the microbial
      community, as shown by reverse sample genome probing. The results indicate that
      the efficiency of inhibitors in containment of SRB depends on the composition and
      metabolic state of the microbial community.

PMID- 11571619
TI  - Volatile hydrocarbon biodegradation by a mixed-bacterial culture during growth on
      crude oil.
AB  - Volatile hydrocarbon biodegradation by a mixed-bacterial culture during growth on
      Bow River crude oil was investigated using solid phase microextraction (SPME).
      Inoculum treatments were examined in relation to C(5)-C(11) hydrocarbon
      degradation. Up to 1600 mg/l biomass (dry weight) was tested without achieving
      significant volatile hydrocarbon partitioning and affecting analysis. Inoculum
      age rather than concentration had the most profound impact on biodegradation.
      When late log phase crude oil-grown inocula were used, C(5)-C(11) biodegradation
      reached 55-60%; methylcyclohexane and other branched compounds eluting before n
      C(8) were recalcitrant. Increasing the late log inoculum concentration from 0.63
      to 63 mg/l resulted in a twofold increase in degradation rate without improving
      the substrate range. Methylcyclohexane recalcitrance was correlated with reduced
      levels of hydrocarbon-degrading bacteria and volatile hydrocarbon evaporation
      from the inoculum flasks. A decreased lag phase prior to degradation was observed
      when using early stationary phase cultures as inocula and most compounds up to
      C(11), including methylcyclohexane, were biodegraded.

PMID- 11571620
TI  - An improved method for determination of ethyl carbamate in Korean traditional
      rice wine.
AB  - An improved extraction method for ethyl carbamate, a genotoxic and carcinogenic
      compound found in various fermented foods and beverages, was investigated for its
      determination in the two most typical Korean traditional rice wines, takju and
      yakju. When the rice wines were extracted twice with chloroform at 30 degrees C
      for 60 min, the recovery of ethyl carbamate was less than 16%. When they were
      saturated with NaCl before extraction, the recovery of ethyl carbamate increased
      to 24.4% in takju and 67.2% in yakju. Adjustment of pH to 9.0 after NaCl
      saturation in takju resulted in a dramatic increase of recovery to 81.2%, but not
      in yakju. When the contents of ethyl carbamate and its precursor, urea, in
      various Korean traditional rice wines were determined, there was no correlation
      between the two contents. This is due to the fact that storage time is more
      important than urea content in the formation of ethyl carbamate in rice wine. In
      addition, its storage at high temperature resulted in a dramatic increase in
      ethyl carbamate content according to the prolonged storage time, suggesting that
      storage time and temperature play a key role in the formation of ethyl carbamate
      in Korean traditional rice wine.

PMID- 11571621
TI  - Convergent and divergent points in catabolic pathways involved in utilization of
      fluoranthene, naphthalene, anthracene, and phenanthrene by Sphingomonas
      paucimobilis var. EPA505.
AB  - Catabolic pathways for utilization of naphthalene (NAP), anthracene (ANT),
      phenanthrene (PHE), and fluoranthene (FLA) by Sphingomonas paucimobilis EPA505
      were identified. Accumulation of catabolic intermediates was investigated with
      three classes of Tn5 mutants with the following polycyclic aromatic hydrocarbon
      (PAH)-negative phenotypes; (class I NAP(-) PHE(-) FLA(-), class II NAP(-) PHE(-),
      and class III FLA(-)). Class I mutant 200pbhA had a Tn5 insertion within a meta
      ring fission dioxygenase (pbhA), and a ferredoxin subunit gene (pbhB) resided
      directly downstream. Mutant 200pbhA and other class I mutants lost the ability to
      catalyze the initial dihydroxylation step and did not transform NAP, ANT, PHE, or
      FLA. Class I mutant 401 accumulated salicylic acid, 2-hydroxy-3-naphthoic acid, 1
      hydroxy-2-naphthoic acid, and hydroxyacenaphthoic acid during incubation with
      NAP, ANT, PHE, or FLA, respectively. Class II mutant 132pbhC contained the Tn5
      insertion in an aldolase hydratase (pbhC) and accumulated what appeared to be
      meta ring fission products: trans-o-hydroxybenzylidene pyruvate, trans-o
      hydroxynaphylidene pyruvate, and trans-o-hydroxynaphthyl-oxobutenoic acid when
      incubated with NAP, ANT, and PHE, respectively. When mutant 132pbhC was incubated
      with 1-hydroxy-2-naphthoic acid, it accumulated trans-o-hydroxybenzylidene
      pyruvate. Class III mutant 104ppdk had a Tn5 insertion in a pyruvate phosphate
      dikinase gene that affected expression of a FLA-specific gene and accumulated a
      proposed meta ring fission product; trans-o-hydroxyacenaphyl-oxobutenoic acid
      during incubation with FLA. Trans-o-hydroxyacenaphyl-oxobutenoic acid was
      degraded to acenaphthenone that accumulated with class III mutant 611.
      Acenaphthenone was oxidized via incorporation of one molecule of dioxygen by
      another oxygenase. 2,3-Dihydroxybenzoic acid was the final FLA-derived catabolic
      intermediate detected. Analysis of PAH utilization mutants revealed that there
      are convergent and divergent points involved in NAP, ANT, PHE, and FLA
      utilization by S. paucimobilis EPA505.

PMID- 11571622
TI  - Enzyme treatment to reduce solids and improve settling of sewage sludge.
AB  - The effect of microbial enzymes in reducing the disposable solid content of
      sludge was investigated. A mixture of industrial cellulase, protease, and lipase,
      in equal proportion by weight, reduced total suspended solids (TSS) by 30-50% and
      improved settling of solids. An increase in solid reduction was observed with
      increasing enzyme concentration. The effect of combinations of enzyme treatments
      indicated that two-enzyme combinations of protease and cellulase produced better
      solid reduction than individual enzymes and that lipase further augmented this
      effect. Among the individual enzymes, protease produced a more settleable sludge
      as compared to cellulase and lipase. Adjustment of the pH of the enzymatically
      treated sludge to the acidic range (pH 2-4) further improved solid reduction, and
      adjustment to the alkaline range (pH 10-12) improved settleability.

PMID- 11571623
TI  - Purification and characterization of two extracellular alkaline proteases from a
      newly isolated obligate alkalophilic Bacillus sphaericus.
AB  - Two novel extracellular serine proteases were purified to homogeneity from the
      cell-free culture filtrate of an obligate alkalophilic Bacillus sphaericus by a
      combination of ultrafiltration, ammonium sulfate precipitation and
      chromatographic methods. The enzymes showed similar substrate specificities, but
      differed in hydrophobicity and molecular mass. Protease A was a monomeric
      protease with a relative molecular mass (M(r)) of 28.7 kDa, whereas protease B,
      with a M(r) of 68.0 kDa, apparently consisted of smaller subunits. The purified
      protease A had a specific activity on hemoglobin of 5.1 U/mg protein compared to
      40.9 U/mg protein in the case of protease B. Both proteases were most active on
      SAAPF-pNa, a substrate for chymotrypsin-like serine proteases. However, the K(m)
      values of these two proteases on SAAPF-pNa were higher than that for alpha
      chymotrypsin, indicating a lower affinity of proteases A and B for this substrate
      compared to chymotrypsin. Unlike other Bacillus serine proteases, neither
      protease A nor B stained with Coomasie blue R-250, even with loading of a large
      amount of protein, and they stained poorly with the silver staining method.
      However, NH(2)-terminal amino acid sequencing of protease B revealed a high
      similarity with subtilisin Carlsberg (67% homology). Almost total inhibition of
      both proteases by PMSF, but very little/no inhibition by trypsin and chymotrypsin
      inhibitors (TPCK and TLCK) or thiol reagents (PCMB and iodoacetic acid), further
      supported the view that the enzyme belonged to the serine protease family.

PMID- 11571627
TI  - Squamous cell carcinoma of the tongue among young Indian adults.
AB  - Oral cancer is one of the commonest cancers among males in India. This study was
      carried out to evaluate the demographics, risk profile, clinicopathologic
      features, and treatment outcome in young patients with squamous cell carcinoma
      (SCC) of the tongue. Patients under the age of 35 years with SCC of the tongue
      presenting between 1982 and 1996 were identified using institutions centralized
      electronic database. Demographic, clinical, and pathologic characteristics were
      abstracted from the case records. Survival was calculated by Kaplan-Meier method.
      One hundred and fifteen patients with histologically confirmed SCC of the tongue
      were analyzed. The mean age at presentation was 30.5 years with a 1.7:1 male to
      female ratio. Prior exposure to tobacco and alcohol was noted in 58 (50.5%)
      patients. At presentation, 70 (60.9%) were in stages III and IV, and 59 (51.3%)
      patients had regional lymph node involvement. The overall disease-free survival
      (DFS) at 3 and 5 years were 63% and 54.9%, respectively. A statistically
      significant difference in DFS was seen between patients with N(0) and N(1)
      disease compared to N(2) or N(3) disease. Various other factors like age, sex,
      habits, and stage of the disease were found to have no significant effect on DFS.
      Results of the present study suggest that contrary to the belief, the survival
      among young patients is almost similar to that in older patients.

PMID- 11571626
TI  - Codon 201(Gly) polymorphic type of the DCC gene is related to disseminated
      neuroblastoma.
AB  - The deleted in colorectal carcinoma (DCC) gene is a potential tumor-suppressor
      gene on chromosome 18q21.3. The relatively high frequency of loss of
      heterozygosity (LOH) and loss of expression of this gene in neuroblastoma,
      especially in the advanced stages, imply the possibility of involvement of the
      DCC gene in progression of neuroblastoma. However, only few typical mutations
      have been identified in this gene, indicating that other possible mechanisms for
      the inactivation of this gene may exist. A polymorphic change (Arg to Gly) at DCC
      codon 201 is related to advanced colorectal carcinoma and increases in the tumors
      with absent DCC protein expression. In order to understand whether this change is
      associated with the development or progression of neuroblastoma, we investigated
      codon 201 polymorphism of the DCC gene in 102 primary neuroblastomas by
      polymerase chain reaction single-strand conformation polymorphism. We found no
      missense or nonsense mutations, but a polymorphic change from CGA (Arg) to GGA
      (Gly) at codon 201 resulting in three types of polymorphism: codon 201(Gly) type,
      codon 201(Arg/Gly) type, and codon 201(Arg) type. The codon 201(Gly) type
      occurred more frequently in disseminated (stages IV and IVs) neuroblastomas (72%)
      than in localized (stages I, II, and III) tumors (48%) (P=.035), and normal
      controls (38%) (P=.024). In addition, the codon 201(Gly) type was significantly
      more common in tumors found clinically (65%) than in those found by mass
      screening (35%) (P=.002). The results suggested that the codon 201(Gly) type of
      the DCC gene might be associated with a higher risk of disseminating
      neuroblastoma.

PMID- 11571628
TI  - Downregulation of Akt1 inhibits anchorage-independent cell growth and induces
      apoptosis in cancer cells.
AB  - The serine/threonine kinases, Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma,
      play a critical role in preventing cancer cells from undergoing apoptosis.
      However, the function of individual Akt isoforms in the tumorigenicity of cancer
      cells is still not well defined. In the current study, we used an Akt1 antisense
      oligonucleotide (AS) to specifically downregulate Akt1 protein in both cancer and
      normal cells. Our data indicate that Akt1 AS treatment inhibits the ability of
      MiaPaCa-2, H460, HCT-15, and HT1080 cells to grow in soft agar. The treatment
      also induces apoptosis in these cancer cells as demonstrated by FACS analysis and
      a caspase activity assay. Conversely, Akt1 AS treatment has little effect on the
      cell growth and survival of normal human cells including normal human fibroblast
      (NHF), fibroblast from muscle (FBM), and mammary gland epithelial 184B5 cells. In
      addition, Akt1 AS specifically sensitizes cancer cells to typical
      chemotherapeutic agents. Thus, Akt1 is indispensable for maintaining the
      tumorigenicity of cancer cells. Inhibition of Akt1 may provide a powerful
      sensitization agent for chemotherapy specifically in cancer cells.

PMID- 11571629
TI  - Alterations in lipoxygenase and cyclooxygenase-2 catalytic activity and mRNA
      expression in prostate carcinoma.
AB  - Recent studies in prostate tissues and especially cell lines have suggested roles
      for arachidonic acid (AA) metabolizing enzymes in prostate adenocarcinoma (Pca)
      development or progression. The goal of this study was to more fully characterize
      lipoxygenase (LOX) and cyclooxygenase-2 (COX-2) gene expression and AA metabolism
      in benign and malignant prostate using snap-frozen tissues obtained
      intraoperatively and mRNA analyses and enzyme assays. Formation of 15
      hydroxyeicosatetraenoic acid (15-HETE) was detected in 23/29 benign samples and
      15-LOX-2 mRNA was detected in 21/25 benign samples. In pairs of pure benign and
      Pca from the same patients, 15-HETE production and 15-LOX-2 mRNA were reduced in
      Pca versus benign in 9/14 (P=.04) and 14/17 (P=.002), respectively. Under the
      same conditions, neither 5-HETE nor 12-HETE formation was detectable in 29 benign
      and 24 tumor samples; with a more sensitive assay, traces were detected in some
      samples, but there was no clear association with tumor tissue. COX-2 mRNA was
      detected by nuclease protection assay in 7/16 benign samples and 5/16 tumors. In
      benign and tumor pairs from 10 patients, COX-2 was higher in tumor versus benign
      in only 2, with similar results by in situ hybridization. Paraffin
      immunoperoxidase for COX-2 was performed in whole mount sections from 87
      additional radical prostatectomy specimens, with strong expression in ejaculatory
      duct as a positive control and corroboration with in situ hybridization. No
      immunostaining was detected in benign prostate or tumor in 45% of cases. Greater
      immunostaining in tumor versus benign was present in only 17% of cases, and
      correlated with high tumor grade (Gleason score 8 and 9 vs. 5 to 7). In
      conclusion, reduced 15-LOX-2 expression and 15-HETE formation is the most
      characteristic alteration of AA metabolism in Pca. Increased 12-HETE and 5-HETE
      formation in Pca were not discernible. Increased COX-2 expression is not a
      typical abnormality in Pca in general, but occurs in high-grade tumors.

PMID- 11571630
TI  - Bcl-2 and M-Myc coexpression increases IGF-IR and features of malignant growth in
      neuroblastoma cell lines.
AB  - The bcl-2 and c-myc oncogenes cooperate to transform multiple cell types. In the
      pediatric malignancy NB(2), Bcl-2 is highly expressed. In tumors with a poor
      prognosis, N-Myc, a protein homologous to c-Myc, is overexpressed as a result of
      gene amplification. The present study was designed to determine whether Bcl-2
      cooperates with N-Myc to bestow a tumorigenic phenotype to neuroblastoma (NB)
      cells. NB cell lines that at baseline express neither Bcl-2 nor N-Myc were stably
      transfected to express these gene products. In this model, we found Bcl-2 rescues
      N-Myc-expressing cells from apoptosis induced by serum withdrawal. Coexpression
      of Bcl-2 and N-Myc supports growth in low serum conditions and anchorage
      independent growth in soft agar. Similarly, in vivo tumorigenic and angiogenic
      activity was dependent on coexpression. Our data further suggests that the
      mechanism underlying these changes involves the receptor for insulin growth
      factor type I (IGF-IR).

PMID- 11571631
TI  - Global methylation profiling of lung cancer identifies novel methylated genes.
AB  - Epigenetic changes, including DNA methylation, are a common finding in cancer. In
      lung cancers methylation of cytosine residues may affect tumor initiation and
      progression in several ways, including the silencing of tumor suppressor genes
      through promoter methylation and by providing the targets for adduct formation of
      polycyclic aromatic hydrocarbons present in combustion products of cigarette
      smoke. Although the importance of aberrant DNA methylation is well established,
      the extent of DNA methylation in lung cancers has never been determined.
      Restriction landmark genomic scanning (RLGS) is a highly reproducible two
      dimensional gel electrophoresis that allows the determination of the methylation
      status of up to 2000 promoter sequences in a single gel. We selected 1184 CpG
      islands for RLGS analysis and determined their methylation status in 16 primary
      non-small cell lung cancers. Some tumors did not show methylation whereas others
      showed up to 5.3% methylation in all CpG islands of the profile. Cloning of 21
      methylated loci identified 11 genes and 6 ESTs. We demonstrate that methylation
      is part of the silencing process of BMP3B in primary tumors and lung cancer cell
      lines.

PMID- 11571632
TI  - Quantitative estimates of vascularity in solid tumors by non-invasive near
      infrared spectroscopy.
AB  - We examined the relationship between non-invasive estimates of the tumor
      hemoglobin concentration by near-infrared spectroscopy (NIRS) and histological
      scores of tumor vascularity by Chalkley counts in seven tumor lines in nude mice
      [malignant gliomas: U87, U118, U373; small cell lung cancers (SCLC): 54A, 54B,
      DMS79; prostate cancer: MatLyLu (MLL)]. We also evaluated the effect of
      continuous anti-angiogenic treatment with TNP-470 on tumor hemoglobin
      concentration and tumor vascularity in U87 and MLL tumors. Non-invasive NIRS
      recordings were performed with a custom-built flash near-infrared spectrometer
      using light guide-coupled reflectance measurements at 800+/-10 nm. Chalkley
      counts were obtained from CD31-immunostained cryosections. The NIRS recordings in
      arbitrary absorbance units increased with tumor size in the individual tumors
      until a plateau was reached at approximately 150 mm(3). This plateau was
      relatively tumor line-specific. NIRS recordings at the plateau phase were
      strongly correlated (P<.001, n=71) to the histological vessel score (Chalkley
      count) of the same individual tumors excised immediately after the NIRS was
      performed. Non-invasive NIRS recordings of the highly vascularized gliomas (U87,
      U118, and U373) plus the MatLyLu tumor line were significantly higher than the
      three less vascularized SCLC tumor lines (P<.001). Continuous treatment with the
      anti-angiogenic compound TNP-470, an endothelial cell inhibitor, significantly
      retarded tumor growth in both U87 and MLL tumors, but all tumors eventually grew.
      When comparing treated and untreated tumors of similar size, both NIRS recordings
      and Chalkley counts were significantly lower in TNP-470-treated tumors (P<.05).
      In conclusion, the NIRS technique provides a non-invasive measure of the degree
      of vascularization in untreated tumors and the NIRS technique can measure
      modifications in tumor vascularization by anti-angiogenic therapy.

PMID- 11571633
TI  - Phenylbutyrate attenuates the expression of Bcl-X(L), DNA-PK, caveolin-1, and
      VEGF in prostate cancer cells.
AB  - Phenylbutyrate (PB) is a histone deacetylase inhibitor that has been shown to
      induce differentiation and apoptosis in various cancer cell lines. Although these
      effects are most likely due to modulation of gene expression, the specific genes
      and gene products responsible for the effects of PB are not well characterized.
      In this study, we used cDNA expression arrays and Western blot to assess the
      effect that PB has on the expression of various cancer and apoptosis-regulatory
      gene products. We show that PB attenuates the expression of the apoptosis
      antagonist Bcl-X(L), the double-strand break repair protein DNA-dependent protein
      kinase, the prostate progression marker caveolin-1, and the pro-angiogenic
      vascular endothelial growth factor. Furthermore, PB was found to act in synergy
      with ionizing radiation to induce apoptosis in prostate cancer cells. Taken
      together, our results point to the possibility that PB may be an effective anti
      prostate cancer agent when used in combination with radiation or chemotherapy and
      for the inhibition of cancer progression.

PMID- 11571634
TI  - Differential utilization and localization of ErbB receptor tyrosine kinases in
      skin compared to normal and malignant keratinocytes.
AB  - Induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF)
      mRNA in mouse skin organ culture was blocked by two pan-ErbB receptor tyrosine
      kinase (RTK) inhibitors but not by genetic ablation of ErbB1, suggesting
      involvement of multiple ErbB species in skin physiology. Human skin, cultured
      normal keratinocytes, and A431 skin carcinoma cells expressed ErbB1, ErbB2, and
      ErbB3, but not ErbB4. Skin and A431 cells expressed more ErbB3 than did
      keratinocytes. Despite strong expression of ErbB2 and ErbB3, heregulin was
      inactive in stimulating tyrosine phosphorylation in A431 cells. In contrast, it
      was highly active in MDA-MB-453 breast carcinoma cells. ErbB2 displayed punctate
      cytoplasmic staining in A431 and keratinocytes, compared to strong cell surface
      staining in MDA-MB-453. In skin, ErbB2 was cytoplasmic in basal keratinocytes,
      assuming a cell surface pattern in the upper suprabasal layers. In contrast,
      ErbB1 retained a cell surface distribution in all epidermal layers. Keratinocyte
      proliferation in culture was found to be ErbB1-RTK-dependent, using a selective
      inhibitor. These results suggest that in skin keratinocytes, ErbB2 transduces
      ligand-dependent differentiation signals, whereas ErbB1 transduces ligand
      dependent proliferation/survival signals. Intracellular sequestration of ErbB2
      may contribute to the malignant phenotype of A431 cells, by allowing them to
      respond to ErbB1-dependent growth/survival signals, while evading ErbB2-dependent
      differentiation signals.

PMID- 11571635
TI  - Telomere lengths and telomerase activity in dog tissues: a potential model system
      to study human telomere and telomerase biology.
AB  - Studies on telomere and telomerase biology are fundamental to the understanding
      of aging and age-related diseases such as cancer. However, human studies have
      been hindered by differences in telomere biology between humans and the classical
      murine animal model system. In this paper, we describe basic studies of telomere
      length and telomerase activity in canine normal and neoplastic tissues and
      propose the dog as an alternative model system. Briefly, telomere lengths were
      measured in normal canine peripheral blood mononuclear cells (PBMCs), a range of
      normal canine tissues, and in a panel of naturally occurring soft tissue tumours
      by terminal restriction fragment (TRF) analysis. Further, telomerase activity was
      measured in canine cell lines and multiple canine tissues using a combined
      polymerase chain reaction/enzyme-linked immunosorbent assay method. TRF analysis
      in canine PBMCs and tissues demonstrated mean TRF lengths to range between 12 and
      23 kbp with heterogeneity in telomere lengths being observed in a range of normal
      somatic tissues. In soft tissue sarcomas, two subgroups were identified with mean
      TRFs of 22.2 and 18.2 kbp. Telomerase activity in canine tissue was present in
      tumour tissue and testis with little or no activity in normal somatic tissues.
      These results suggest that the dog telomere biology is similar to that in humans
      and may represent an alternative model system for studying telomere biology and
      telomerase-targeted anticancer therapies.

PMID- 11571638
TI  - FLRG, an activin-binding protein, is a new target of TGFbeta transcription
      activation through Smad proteins.
AB  - The FLRG gene encodes a secreted glycoprotein that binds to activin and is highly
      homologous to follistatin, an activin ligand. We cloned the promoter region of
      the human FLRG gene, and defined the minimal region necessary for transcription
      activation in a reporter-system assay. We showed that the fragment between
      positions -130 and +6, which consists of multiple consensus Sp1-binding sites, is
      required for the constitutive expression of the FLRG gene. We demonstrate here
      that FLRG mRNA expression is rapidly induced by TGFbeta or by transfection with
      Smad protein expression vectors in human HepG2 cells. We investigated the
      transcription-regulation mechanism of FLRG expression in HepG2 cells following
      treatment with TGFbeta. By deletion and point-mutation analysis of the FLRG
      promoter, we identified a Smad-binding element involved in the TGFbeta-inducible
      expression of the FLRG gene. Moreover, transactivation of the FLRG promoter by
      TGFbeta was compromised by dominant-negative mutants of Smad3 and Smad4 proteins.
      In addition, gel electrophoresis mobility-shift assays demonstrated the specific
      interaction of Smad3 and Smad4 proteins with the Smad-binding element consensus
      motif found in the FLRG promoter. Taken together, our data imply that Smad
      proteins participate in the regulation of expression of FLRG, a new target of
      TGFbeta transcription activation.

PMID- 11571636
TI  - Chemosensitization of human renal cell cancer using antisense oligonucleotides
      targeting the antiapoptotic gene clusterin.
AB  - BACKGROUND: Renal cell cancer (RCC) is a chemoresistant disease with no active
      chemotherapeutic agent achieving objective response rates higher than 15%.
      Clusterin is a cell survival gene that increases in human renal tubular
      epithelial cells after various states of injury and disease. Downregulation of
      clusterin, using antisense oligonucleotides (ASO), has recently been shown to
      increase chemosensitivity in several prostate cancer models. The objectives in
      this study were to evaluate clusterin expression levels in human RCC and normal
      kidney tissue, and to test whether clusterin ASO could also enhance
      chemosensitivity in human RCC Caki-2 cells both in vitro and in vivo. METHODS:
      Immunohistochemical staining was used to characterize clusterin expression in 67
      RCC and normal kidney tissues obtained from radical nephrectomy specimens.
      Northern blot analysis was used to assess changes in clusterin mRNA expression
      after ASO and paclitaxel treatment. The effects of combined clusterin ASO and
      paclitaxel treatment on Caki-2 cell growth was examined using an MTT assay.
      Athymic mice bearing Caki-2 tumors were treated with clusterin ASO alone,
      clusterin ASO plus paclitaxel, and mismatch control oligonucleotides plus
      paclitaxel, over a period of 28 days with measurement of tumor volumes once
      weekly over 8 weeks. RESULTS: Immunohistochemistry of normal and malignant kidney
      tissue sections of 67 patients demonstrated positive clusterin staining for
      almost all RCC (98%) and an overexpression, compared to normal tissue, in a
      majority of RCC (69%). Clusterin ASO, but not mismatch control oligonucleotides,
      decreased clusterin mRNA expression in Caki-2 cells in a dose-dependent and
      sequence-specific manner. Pretreatment of Caki-2 cells with clusterin ASO
      significantly enhanced chemosensitivity to paclitaxel in vitro. Characteristic
      apoptotic DNA laddering was observed after combined treatment with ASO plus
      paclitaxel, but not with either agent alone. In vivo administration of clusterin
      ASO plus paclitaxel acted synergistically to increase apoptosis and significantly
      delay Caki-2 tumor growth, compared to mismatch control oligonucleotide plus
      paclitaxel. In addition, TUNEL staining revealed increased apoptotic cells in
      tumors treated with clusterin ASO plus paclitaxel compared to treatment with
      either clusterin ASO or paclitaxel alone. CONCLUSION: These findings confirm that
      the use of clusterin ASO may be a feasible strategy to enhance chemosensitivity
      for patients with advanced RCC.

PMID- 11571639
TI  - Membrane-associated binding sites for estrogen contribute to growth regulation of
      human breast cancer cells.
AB  - Membrane-associated binding sites for estrogen may mediate rapid effects of
      estradiol-17beta that contribute to proliferation of human breast cancers. After
      controlled homogenization and fractionation of MCF-7 breast cancer cells, the
      bulk of specific estradiol binding is found in nuclear fractions. However, a
      significant portion of specific, high-affinity estradiol-17beta binding-sites are
      also enriched in plasma membranes. These estradiol binding-sites co-purify with
      5'-nucleotidase, a plasma membrane-marker enzyme, and are free from major
      contamination by cytosol or nuclei. Electrophoresis of membrane fractions allowed
      detection of a primary 67-kDa protein and a secondary 46-kDa protein recognized
      by estradiol-17beta and by a monoclonal antibody directed to the ligand-binding
      domain of the nuclear form of estrogen receptor. Estrogen-induced growth of MCF-7
      breast cancer cells in vitro was blocked by treatment with the antibody to
      estrogen receptor and correlated closely with acute hormonal activation of
      mitogen-activated protein kinase and Akt kinase signaling. Estrogen-promoted
      growth of human breast cancer xenografts in nude mice was also significantly
      reduced by treatment in vivo with the estrogen receptor antibody. Thus, membrane
      associated forms of estrogen receptor may play a role in promoting intracellular
      signaling for hormone-mediated proliferation and survival of breast cancers and
      offer a new target for antitumor therapy.

PMID- 11571640
TI  - HPV E6 and MAGUK protein interactions: determination of the molecular basis for
      specific protein recognition and degradation.
AB  - It has recently been shown that the high-risk human papillomavirus (HPV) E6
      proteins can target the PDZ-domain containing proteins, Dlg, MUPP-1, MAGI-1 and
      hScrib for proteasome-mediated degradation. However, the E6 proteins from HPV-16
      and HPV-18 (the two most common high-risk virus types) differ in their ability to
      target these proteins in a manner that correlates with their malignant potential.
      To investigate the underlying mechanisms for this, we have mutated HPV-16 and HPV
      18 E6s to give each protein the other's PDZ-binding motif. Analysis of these
      mutants shows that the greater ability of HPV-18 E6 to bind to these proteins and
      to target them for degradation is indeed due to a single amino acid difference.
      Using a number of assays, we show that the E6 proteins interact specifically with
      only one of the five PDZ domains of MAGI-1, and this is the first interaction
      described for this particular PDZ domain. We also show that the guanylate kinase
      homology domain and the regions of MAGI-1 downstream of amino acid 733 are not
      required for the degradation of MAGI-1. Finally, in a series of comparative
      analyses, we show that the degradation of MAGI-1 occurs through a different
      mechanism from that used by the E6 protein to induce the degradation of Dlg and
      p53.

PMID- 11571641
TI  - HoxB8 requires its Pbx-interaction motif to block differentiation of primary
      myeloid progenitors and of most cell line models of myeloid differentiation.
AB  - HoxB8 was the first homeobox gene identified as a cause of leukemia. In murine
      WEHI3B acute myeloid leukemia (AML) cells, proviral integration leads to the
      expression of both HoxB8 and Interleukin (IL-3). Enforced expression of HoxB8
      blocks differentiation of factor-dependent myeloid progenitors, while IL-3 co
      expression induces autocrine proliferation and overt leukemogenicity. Previously,
      we demonstrated that HoxB8 binds DNA cooperatively with members of the Pbx family
      of transcription factors, and that HoxB8 makes contact with the Pbx homeodomain
      through a hexameric sequence designated the Pbx-interaction motif (PIM). E2a
      Pbx1, an oncogenic derivative of Pbx1, both retains its ability to heterodimerize
      with Hox proteins and arrest myeloid differentiation. This observation prompts
      the question of whether E2a-Pbx1 and Hox oncoproteins use endogenous Hox and Pbx
      proteins, respectively, to target a common set of cellular genes. Here, we use
      four different models of neutrophil and macrophage differentiation to determine
      whether HoxB8 needs to bind DNA or Pbx cofactors in order to arrest myeloid
      differentiation. The ability of HoxB8 to bind DNA or to bind Pbx was essential
      (1) to block differentiation of factor-dependent myeloid progenitors from primary
      marrow; (2) to block IL-6-induced monocytic differentiation of M1-AML cells; and
      (3) to block granulocytic differentiation of GM-CSF-dependent ECoM-G cells.
      However, while DNA-binding was required, the HoxB8 Pbx-interaction motif was
      unnecessary for preventing macrophage differentiation of ECoM-M cells. We
      conclude that HoxB8 prevents differentiation by directly influencing cellular
      gene expression, and that the genetic context within a cell dictates whether the
      effect of HoxB8 is dependent on a physical interaction with Pbx proteins.

PMID- 11571642
TI  - p53 binds the nuclear matrix in normal cells: binding involves the proline-rich
      domain of p53 and increases following genotoxic stress.
AB  - The tumour suppressor p53 is a multifunctional protein important for the
      maintenance of genomic integrity. It is able to form molecular complexes with
      different DNA targets and also with cellular proteins involved in DNA
      transcription and DNA repair. In mammalian cells the biochemical processing of
      DNA occurs on a nuclear sub-structure termed the nuclear matrix. Previously
      Deppert and co-workers have identified p53 in association with the nuclear matrix
      in viral- and non-viral transformed cell lines. In the present study we
      demonstrate, for the first time, that p53 is bound to the nuclear matrix in
      primary cultures of normal mammalian cells and that this binding increases
      following DNA damage. Analysis of cell lines expressing structural mutants of p53
      revealed that association with the nuclear matrix is independent of the tertiary
      and quaternary structure of p53. However, the proline-rich domain towards the N
      terminus of p53 (residues 67 to 98) appeared important for binding to the nuclear
      matrix. This was demonstrated by TET-ON regulated expression of p53-derived
      constructs in p53(-/-) murine embryonic fibroblasts (MEF p53(-/-)). The proline
      rich domain of p53 has potential for SH3 protein-protein interaction, and has a
      role in p53-mediated apoptosis and possibly base excision repair of DNA damage.
      We discuss our observations in relation to the ability of p53 to facilitate DNA
      repair and also review evidence indicating that matrix-bound p53 in SV40
      transformed cells may facilitate the transforming potential of SV40 large T
      antigen.

PMID- 11571643
TI  - Mammary glands reconstituted with Neu/ErbB2 transformed HC11 cells provide a
      novel orthotopic tumor model for testing anti-cancer agents.
AB  - The ErbB2 receptor tyrosine kinase (RTK) has been intensely pursued as a cancer
      therapy target due to its association with breast cancer. In this study we used
      the HC11 mammary epithelial cell line to develop an orthotopic, ErbB2-driven
      tumor model for testing efficacy of anti-cancer compounds. HC11 cells were
      infected with a retrovirus encoding oncogenic NeuT, the rat homolog of ErbB2.
      Drug-selected populations were introduced into mammary fat pads of Balb/c
      syngeneic mice cleared of host tissue. The majority of glands injected with HC11
      NeuT cells developed mammary tumors which appeared after a 3-4 week latency
      period and grew rapidly. HC11 cells infected with the control retrovirus showed
      no tumor growth after injection. Tumor-bearing mice were used to compare the in
      vivo efficacy of two anti-cancer agents: PKI166, a kinase inhibitor selective for
      EGF receptor and ErbB2, and Taxol, a microtubule assembly blocker. PKI166
      inhibited NeuT-induced mammary tumor growth in a dose-dependent manner and at a
      dose below the maximum tolerated dose (MTD) was significantly more inhibitory
      than Taxol at its MTD (57% vs. 25% tumor regression). Importantly, there was a
      dose-dependent decrease in the phosphotyrosine content of NeuT isolated from
      PKI166-treated, tumor-bearing mice, providing a mechanistic link between kinase
      inhibition and its anti-tumor activity. Thus, implantation of genetically
      manipulated HC11 cells into mammary glands appears to be an excellent model for
      studying effects of anti-cancer agents in an orthotopic site.

PMID- 11571644
TI  - Human wig-1, a p53 target gene that encodes a growth inhibitory zinc finger
      protein.
AB  - We previously identified a novel p53-induced mouse gene, wig-1, that encodes a
      290 amino acid zinc finger protein (Varmeh-Ziaie et al., 1997). Here we have
      identified and characterized the human homolog of mouse wig-1. The human wig-1
      protein is 87% identical to the mouse protein and contains three zinc finger
      domains and a putative nuclear localization signal. Human wig-1 mRNA and protein
      is induced following activation of wild type p53 expression in our BL41-ts p53
      Burkitt lymphoma cells. Wig-1 is also induced in MCF7 cells following treatment
      with the DNA-damaging agent mitomycin C. Northern blotting detected low levels of
      wig-1 mRNA in normal human tissues. Fluorescence in situ hybridization mapped wig
      1 to human chromosome 3q26.3-27. FLAG-tagged human wig-1 localizes to the
      nucleus. Ectopic overexpression of human wig-1 inhibits tumor cell growth in a
      colony formation assay. These results suggest that human wig-1 has a role in the
      p53-dependent growth regulatory pathway.

PMID- 11571645
TI  - Cloning and characterization of a novel transcription factor involved in cellular
      proliferation arrest: PATF.
AB  - Cell cycle withdrawal involves several transcription factors such as E2Fs members
      that play a key role in cell growth control. Here we describe a novel putative
      bZIP transcription factor isolated from the retina and involved in neuronal
      proliferation arrest at the terminal differentiation: PATF (Proliferation Arrest
      Transcription Factor). We show that PATF associates with E2F4 protein and
      interacts with the E2F consensus site. PATF expression increases with
      establishment of quiescent state. Furthermore, the nuclear PATF localization like
      E2F4, depends on cell growth arrest. The decrease of PATF amount, using a
      retroviral antisense strategy, results in pursued neuroretina cell mitosis. Our
      results indicate that PATF could be a new molecular signal implicated in the
      final neuronal cell cycle withdrawal.

PMID- 11571646
TI  - Germ-line deletion of p53 reveals a multistage tumor progression in spi-1/PU.1
      transgenic proerythroblasts.
AB  - Activation of the spi-1/PU.1 proto-oncogene and loss of p53 function are genetic
      alterations associated with the emergence of Friend malignant erythroleukemic
      cells. To address the role of p53 during erythroleukemogenesis, spi-1 transgenic
      mice (spi-1-Tg) which develop erythroleukemia were bred with p53-deficient mice.
      Three classes of spi-1 transgenic mice differing in their p53 functional status
      (p53(+/+), p53(+/-) and p53(-/-)) were generated. These mice developed a unique
      pattern of erythroleukemia. In wild-type p53 spi-1-Tg mice, none of the primary
      erythroleukemic spleen cells displayed autonomous growth in vitro and in vivo. In
      contrast, in p53(+/-) spi-1-Tg mice, erythroleukemic cells gave rise to growth
      factor-independent cell lines and generated tumors in vivo. Malignancy was
      associated with loss of the wild-type p53 allele. The p53(-/-) spi-1-Tg mice
      developed erythroleukemia with a total incidence and a reduced latency compared
      to the two other genotypes. Unexpectedly, 50% of p53(-/-) spi-1-Tg
      erythroleukemic spleens generated cell lines that were strictly dependent upon
      erythropoietin (Epo) for proliferation, whereas the remainder proliferated
      independently of cytokines. Moreover, only 70% of these spleen cells were
      tumorigenic. These findings indicate that p53 germ-line deletion did not confer
      malignancy to spi-1-transgenic proerythroblasts. Moreover Epo independence and
      tumorigenicity appear as separable phenotypic characteristics revealing that the
      spi-1-Tg proerythroblasts progress towards malignancy through multiple oncogenic
      events.

PMID- 11571647
TI  - Differential requirement of the last C-terminal tail of Met receptor for cell
      transformation and invasiveness.
AB  - Biological responses to Hepatocyte Growth Factor are mediated by the tyrosine
      kinase receptor encoded by the Met oncogene. Under physiological conditions, Met
      triggers a multi-step genetic program called 'invasive growth' including cell
      dissociation, invasion of extracellular matrices and growth. When constitutively
      activated, Met can induce cell transformation and metastasis. Phosphorylation of
      two docking tyrosines in the receptor tail is essential for all biological
      responses. To investigate the role of the C-terminal part of Met, we have
      generated mutants lacking either the last 26 or 47 amino acids. As expected,
      mutants lacking the docking sites fail to mediate cell transformation and
      invasion. Interestingly, while Met Delta26 can mediate invasion, its transforming
      ability is severely impaired. Moreover, the lack of the last 26 amino acids
      strongly reduces Met ability to phosphorylate substrates in vitro and in vivo.
      These data indicate that the last 26 amino acids are required to confer the
      kinase its full enzymatic activity, which is critical for cell transformation but
      dispensable for invasive properties. Finally, we also show that up-regulation of
      Met enzymatic activity by insertion of a point mutation in the kinase domain
      (M1250T) overcomes the regulatory role played by the last 26 amino acids of the
      tail. It is concluded that the C-terminal domain of Met is crucial not only for
      recruitment of transducers but also for regulation of receptor enzymatic
      activity.

PMID- 11571648
TI  - Functional impact of concomitant versus alternative defects in the Chk2-p53
      tumour suppressor pathway.
AB  - Recent evidence identified a genetic and functional link between Chk2 kinase and
      p53 as a candidate genome integrity checkpoint and a tumour suppressor pathway.
      Here we report that in human cells, Chk2 and p53 form protein-protein complexes
      whose abundance increased upon DNA damage, and whose formation was abrogated
      through cancer associated mutations in the FHA domain of Chk2, or mutations in
      the tetramerization domain of p53. Whereas among Li-Fraumeni syndrome families
      mutations of Chk2 or p53 occur in a mutually exclusive manner, we document that
      the colon cancer cell line HCT-15 concomitantly lacks functions of both Chk2 and
      p53, the latter demonstrated by a non-invasive reporter assay monitoring p53
      dependent transactivation in live cells. Despite the preserved ability of common
      cancer-derived mutant p53 proteins to bind and potentially 'titrate' activated
      Chk2, the integrity of the S phase checkpoint response to ionizing radiation
      remained largely intact and dependent on Chk2 in cells with wild-type, mutant, or
      no p53. These results provide new mechanistic insights into the Chk2-p53
      interplay, suggest how mutations in Chk2 may abrogate its tumour suppressor
      function, and indicate that compared with individual defects in either Chk2 or
      p53, concomitant mutations in both of these cell cycle checkpoint regulators may
      provide some additional selective advantage to tumour cells.

PMID- 11571649
TI  - VEGF(165) requires extracellular matrix components to induce mitogenic effects
      and migratory response in breast cancer cells.
AB  - The expression of VEGF and the relapse-free survival rate of breast cancer
      patients are inversely related. While VEGF induces the proliferation and
      migration of vascular endothelial cells, its function in breast cancer cells is
      not well studied. We reported previously that fibronectin increased VEGF
      dependent migration in breast cancer cells. Since VEGF has an extracellular
      matrix (ECM)-binding domain and possesses binding affinity for heparin, we sought
      to determine the effects of VEGF in breast cancer cells and the role of heparin
      and/or fibronectin in VEGF-induced signaling. Cells grown on plastic were
      compared to those grown on fibronectin or to those grown on plastic in the
      presence of heparin, and analysed for intracellular signaling, proliferation and
      migration in response to VEGF(165). Both heparin and fibronectin enhanced the
      binding of VEGF to T47D cells. After treatment with VEGF, [(3)H]thymidine
      incorporation, c-fos induction, and the number of migrating cells were
      significantly higher ( approximately twofold) in cells grown on fibronectin or in
      cells grown on plastic in the presence of heparin when compared to those grown on
      plastic only. Likewise, tyrosine phosphorylation of VEGF receptors, MAPK activity
      and PI3-kinase activity were all several-fold higher in cells seeded on
      fibronectin or in the presence of heparin as compared to cells exposed to VEGF
      alone. VEGF-dependent c-fos induction was found to be regulated through a MAPK
      dependent, but PI3-kinase-independent pathway. In contrast, the migration of T47D
      cells in response to VEGF, in the presence of ECM, was regulated through PI3
      kinase. Therefore, VEGF requires ECM components to induce a mitogenic response
      and cell migration in T47D breast cancer cells.

PMID- 11571650
TI  - A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in
      scirrhous gastric carcinoma.
AB  - Scirrhous carcinoma of the stomach is characterized by rapid growth with a vast
      fibrous stroma, high invasiveness, and substantially a poor prognosis. Little is
      known of the molecular pathogenesis of this disease. Members of the emerging
      family of the CCN gene (for connective tissue growth factor, cysteine-rich 61,
      nephroblastoma overexpressed) encode cysteine-rich secreted proteins with roles
      in human fibrotic disorders and cancer progression. Using targeted differential
      displays, we identified a novel variant of the CCN family member WISP1 (Wnt
      induced secreted protein 1), named WISP1v, as overexpressed in scirrhous gastric
      carcinomas. Predicted protein of the WISP1v completely lacks a module of Von
      Willebrand type C that is thought to participate in protein complex formation.
      Ectopic expression revealed WISP1v to be a secreted oncoprotein inducing a
      striking cellular transformation and rapid piling-up growth. It is noteworthy
      that WISP1v transfectants enhanced the invasive phenotype of co-cultured gastric
      carcinoma cells, while wild-type WISP1 had no such potential. These findings
      suggest that CCN protein WISP1v is involved in the aggressive progression of
      scirrhous gastric carcinoma.

PMID- 11571651
TI  - Association of UNP, a ubiquitin-specific protease, with the pocket proteins pRb,
      p107 and p130.
AB  - The murine Unp gene encodes a widely expressed ubiquitin-specific protease. The
      predicted sequence of the UNP protein features motifs common to viral
      oncoproteins through which these proteins interact with the retinoblastoma gene
      product pRb, as well as the related 'pocket proteins' p107 and p130. We have
      explored the possibility that UNP interacts with pocket proteins, and report here
      that such associations can be detected in vitro and in cells. Associations of UNP
      and pocket proteins are sensitive to site-directed mutations in a manner directly
      analogous to those documented in viral oncoproteins. We conclude that within
      cells UNP does physically associate with pRb, and can also associate with p107
      and p130.

PMID- 11571652
TI  - The de-ubiquitinating enzyme Unp interacts with the retinoblastoma protein.
AB  - The ubiquitin pathway is involved in the proteolytic turnover of many short-lived
      cellular regulatory proteins. Since selective degradation of substrates of this
      system requires the covalent attachment of a polyubiquitin chain to the
      substrates, degradation could be counteracted by de-ubiquitinating enzymes (or
      isopeptidases) which selectively remove the polyubiquitin chain. Unp is a human
      isopeptidase with still poorly understood biological functions. Here, we show
      that cellular Unp specifically interacts with the retinoblastoma gene product
      (pRb).

PMID- 11571654
TI  - Sporadic testicular germ cell cancers do not exhibit specific alteration in
      CAG/CTG repeats containing genes expressed in human testis.
AB  - CAG/CTG repeat expansions in genomic DNA of testicular tumour cell lines, and
      germline DNA from members of families predisposed to this malignancy, have been
      previously described. In order to identify genes possibly concerned by this
      alteration, we attempted to clone all possible human testis cDNA containing at
      least five CAG/CTG repeats. Thirty-four different transcripts were identified. By
      using PCR and non denaturing gel electrophoresis, we determined the size of their
      repeats, as well as their polymorphisms in a collection of human testicular germ
      cell tumours and the normal surrounding tissues. For all tested genes, we
      detected the presence of several species of the same mRNA for each person. Nine
      genes exhibited specific patterns of expression among different groups of
      individuals, indicative of polymorphism. None of these polymorphisms was related
      to human testicular tumours.

PMID- 11571653
TI  - A melanoma-associated germline mutation in exon 1beta inactivates p14ARF.
AB  - The INK4a/ARF locus encodes the cyclin dependent kinase inhibitor, p16(INK4a) and
      the p53 activator, p14ARF. These two proteins have an independent first exon
      (exon 1alpha and exon 1beta, respectively) but share exons 2 and 3 and are
      translated in different reading frames. Germline mutations in this locus are
      associated with melanoma susceptibility in 20-40% of multiple case melanoma
      families. Although most of these mutations specifically inactivate p16(INK4a),
      more than 40% of the INK4a/ARF alterations located in exon 2, affect both
      p16(INK4a) and p14ARF. We now report a 16 base pair exon 1beta germline insertion
      specifically altering p14ARF, but not p16(INK4a), in an individual with multiple
      primary melanomas. This mutant p14ARF, 60ins16, was restricted to the cytoplasm,
      did not stabilize p53 and was unable to arrest the growth of a p53 expressing
      melanoma cell line. This is the first example of an exon 1beta mutation that
      inactivates p14ARF, and thus implicates a role for this tumour suppressor in
      melanoma predisposition.

PMID- 11571655
TI  - Conserved synteny between the Fugu and human PTEN locus and the evolutionary
      conservation of vertebrate PTEN function.
AB  - Mutations of PTEN, which encodes a protein-tyrosine and lipid phosphatase, are
      prevalent in a variety of human cancers. The human genome 'draft' sequence still
      lacks organization and much of the PTEN and adjacent loci remain undefined. The
      pufferfish, Fugu rubripes, by virtue of having a compact genome represents an
      excellent template for rapid vertebrate gene discovery. Sequencing of 56 kb from
      the Fugu pten (fpten) locus identified four complete genes and one partial gene
      homologous to human genes. Genes neighboring fpten include a PAPS synthase
      (fpapss2) differentially expressed between non-metastatic/metastatic human
      carcinoma cell lines, an inositol phosphatase (fminpp1) and an omega class
      glutathione-S-transferase (fgsto). We have determined the order of human BAC
      clones at the hPTEN locus and that the locus contains hPAPSS2 and hMINPP1 genes
      oriented as are their Fugu orthologs. Although the human genes span 500 kb, the
      Fugu genes lie within only 22 kb due to the compressed intronic and intergenic
      regions that typify this genome. Interestingly, and providing striking evidence
      of regulatory element conservation between widely divergent vertebrate species,
      the compact 2.1 kb fpten promoter is active in human cells. Also, like hPTEN,
      fpten has a growth and tumor suppressor activity in human glioblastoma cells,
      demonstrating conservation of protein function.

PMID- 11571656
TI  - WNK kinases, a novel protein kinase subfamily in multi-cellular organisms.
AB  - We have cloned and characterized a novel human serine/threonine protein kinase
      gene from chromosome 12p13.3 encoding 2382 amino acids. Remarkably, the catalytic
      domain sequence contains a cysteine in place of a lysine residue conserved in
      subdomain II of most kinases. The same amino acid alteration was recently
      described for rat WNK1 (with no K=lysine) in which another nearby lysine residue
      was shown to confer kinase activity to the protein. Rat WNK1 is 85% identical to
      a splice variant lacking exons 11 and 12 of the described human kinase which we
      have called human WNK1. The WNK1 catalytic domain has closest homology with human
      PAK2, MEKK3, and Raf-1. Three additional, partial human protein kinase sequences,
      WNK2, WNK3 and WNK4, are also reported here with catalytic domains that are 95%
      homologous to WNK1. These genes differ both in chromosomal location and tissue
      specific expression. Moreover, we have identified in the database a total of 18
      WNK-related genes, all exclusively from multi-cellular organisms, which share a
      WNK kinase sequence signature within subdomains I and II of the catalytic domain.
      We suggest that they constitute a novel subfamily of protein kinases that evolved
      together with cell adhesion and tissue-formation.

PMID- 11571657
TI  - Sexual function in spinal cord lesioned men.
AB  - STUDY DESIGN: Review of literature. OBJECTIVE: To review the physical aspects
      related to penile erection, ejaculatory dysfunction, semen characteristics, and
      techniques for enhancement of fertility in spinal cord lesioned (SCL) men.
      SETTING: Worldwide: individuals with traumatic as well as non-traumatic SCL.
      RESULTS: Recommendations for management of erectile dysfunction in SCL men: If it
      is possible to obtain a satisfactory erection but of insufficient duration, then
      try to use a venous constrictor band to find out if this is sufficient to
      maintain the erection. Otherwise we recommend Sildenafil. If Sildenafil is not
      satisfactory then use intracavernous injection with prostaglandin E(1) (some SCL
      men may prefer cutaneous or intraurethral application). We discourage the
      implantation of penile prosthesis for the sole purpose of erection.
      Recommendations for management of ejaculatory dysfunction in SCL men: Penile
      vibratory stimulation (PVS) to induce ejaculation is recommended as first
      treatment choice. If PVS fails, SCL men should be referred for electroejaculation
      (EEJ). Semen characteristics: Impaired semen profiles with low motility rates are
      seen in the majority of SCL men. Recently reported data gives evidence of a
      decline in spermatogenesis and motility of ejaculated spermatozoa shortly after
      (few weeks) an acute SCL. It is suggested that some factors in the seminal plasma
      and/or disordered storage of spermatozoa in the seminal vesicles are mainly
      responsible for the impaired semen profiles in men with chronic SCL. Fertility:
      Home insemination with semen obtained by PVS and introduced intravaginally in
      order to achieve successful pregnancies may be an option for some SCL men and
      their partners. The majority of SCL men will further enhance their fertility
      potential when using either PVS or EEJ combined with assisted reproduction
      techniques such as intrauterine insemination or in vitro fertilization with or
      without intracytoplasmic sperm injection.

PMID- 11571659
TI  - Perinephric abscesses in the neurologically impaired.
AB  - STUDY DESIGN: Retrospective chart review. OBJECTIVES: To document the occurrence
      and management of large perinephric abscesses in neurologically impaired patients
      at high risk for this infectious complication. SETTING: US Veterans Affairs
      hospital. METHODS: The records, radiographs, operative findings and outcomes of
      all patients who presented with perinephric abscesses evident on physical exam
      within the last 5 years were reviewed. RESULTS: Four patients presented with
      large perinephric abscesses evident on physical examination. All had severe
      neurologic impairment with high sensory levels; three had spinal cord injuries,
      one had advanced multiple sclerosis. All had neurogenic bladders and recurrent
      urinary tract infections. The diagnosis was made through a combination of
      history, physical examination and computed tomography (CT) examination. All were
      found to have upper tract obstruction. All were managed with immediate abscess
      drainage and three had elective nephrectomy once the infection had resolved. No
      patients died of their perinephric abscess. CONCLUSIONS: These four cases
      illustrate that although advances in antibiotics, imaging and percutaneous
      management have improved the speed of diagnosis and reduced the mortality in
      patients with perinephric abscesses, the neurologically impaired population
      continues to remain at significant risk for the development and the delayed
      diagnosis of these morbid renal infections.

PMID- 11571658
TI  - Is methyl prednisolone useful in acute transverse myelitis?
AB  - STUDY DESIGN: Hospital based observational study. OBJECTIVES: To evaluate the
      role of methyl prednisolone (MPS) in the management of acute transverse myelitis
      (ATM). METHODS: Twenty-one patients with ATM were included in a prospective
      hospital based study during 1992-1997. All the patients underwent neurological
      examination, spinal MRI, somatosensory and motor evoked potentials of both upper
      and lower limbs and concentric needle EMG study. Twelve consecutive patients did
      not receive MPS therapy who were managed during 1992-1994 and nine consecutive
      patients during 1995-1997 received MPS therapy in a dose of 500 mg i.v. for 5
      days. The clinical and neurophysiological studies were repeated 3 months later.
      The outcome was defined on the basis of Barthel index (BI) score at the end of 3
      months into good (BI> or =12) and poor (BI<12). RESULTS: The age of MPS group was
      25.5 years (range 12-42) and three were females. The age of non MPS group was
      33.5 years (range 16-70) and two were females. In the MPS group 33% had poor
      outcome compared to 67% in the non MPS group. In the MPS group mean admission BI
      score was 7.3 which improved to 14.6 after MPS therapy. In the non MPS group, the
      admission BI score was 3.2 which improved to 9.6 at 3 month follow-up. In
      patients with complete paraplegia, evidence of denervation on EMG and
      unrecordable central motor conduction time to lower limb and tibial SEP were
      associated with poor outcome irrespective of MPS treatment. Global test
      statistics did not suggest a beneficial role of MPS therapy in the outcome of
      ATM. CONCLUSION: Our results do not suggest a beneficial role of methyl
      prednisolone on the 3 month outcome of ATM.

PMID- 11571660
TI  - Spinal cord decompression: an endoscopically assisted approach for metastatic
      tumors.
AB  - STUDY DESIGN: The paper describes a technique for complete vertebrectomy and
      spinal cord decompression, followed by a formal anterior column reconstruction,
      using endoscopic instruments. This procedure is indicated for patients with
      radioresistant metastasis of the thoracic spine, particularly those involving the
      upper thoracic segments where a thoracotomy is difficult and carries a high
      morbidity, and for patients with pulmonary disease who cannot tolerate a standard
      thoracotomy. Results in nine consecutive cases are reported. OBJECTIVES: To
      demonstrate the feasibility and benefits of endoscopically assisted decompression
      and stabilization through a single, extrapleural, posterolateral approach.
      SETTING: The Cleveland Clinic, Cleveland, Ohio, USA. METHODS: Posterolateral
      decompression of the thoracic spinal cord offers potential advantages over
      traditional combined procedures (anterior thoracotomy and posterior
      instrumentation), including reduced operative time, decreased morbidity, and
      reduced hospital stay. Previous studies have not demonstrated the same
      neurological benefit for posterolateral decompression as for anterior
      vertebrectomy and decompression, however, Surgical indications, rationale and
      technique for an improved posterolateral approach, augmented by endoscopic
      methods, are provided, and initial clinical results are described. RESULTS:
      Drawbacks to the traditional posterolateral decompressions have included poor
      visualization of the spinal cord and anterior tumor, poor access to tumor on the
      side contralateral to the approach, and the need to manipulate the spinal cord to
      completely remove both adjacent tumor and tumor adherent to the dura.
      Transpedicular decompression using endoscopy is described in nine patients. The
      mean operative time for the combined procedure was 6.0 h, with a mean blood loss
      of 1677 cc. Neurological recovery and maintenance were excellent. Inpatient days
      averaged 6.5, and ICU days averaged 1.4. Two patients died of disease eight and
      14 months post-op, and seven were living, with disease, 3-36 months after
      surgery. CONCLUSIONS: Endoscopically assisted decompression can reduce morbidity,
      hospitalization, and treatment costs while matching the efficacy of traditional
      combined procedures. Endoscopy provides a readily available and easily applied
      tool that dramatically improves the surgeon's vision, providing light,
      magnification, and a direct view of remote structures.

PMID- 11571661
TI  - Myxomatous degeneration of the ligamentum flavum of the lumbar spine.
AB  - STUDY DESIGN: Report of two cases of acute lumbar nerve root compression caused
      by myxomatous degeneration of the ligamentum flavum. OBJECTIVE: To report a rare
      cause of acute lumbar nerve root compression. SETTING: Orthopaedic department,
      Osaka, Japan. SUMMARY OF BACKGROUND DATA: Two patients, both 50-year-old men
      presenting with signs and symptoms suggestive of acute lumbar nerve root
      compression were found to have a ligamentum flavum mass. The masses were removed
      and the patients regained normal function postoperatively. METHODS: To reveal the
      nature of the mass, histopathological studies were made. Continuous sections were
      prepared from the removed mass lesions. The sections were stained with
      hematoxylin and eosin, van Gieson's stain, azan stain, periodic acid Schiff
      reaction, Alcian blue stain and von Kossa's stain. RESULTS: Histological
      examination revealed myxomatous degeneration of the ligamentum flavum. No elastic
      fibers were found at the degeneration site. Diffuse mucopolysaccharide deposition
      was found at the degeneration site, however, no cyst was found. Collagen fibers
      were not increased. Hypertrophy or ossification of the ligamentum flavum was not
      recognized in the sections. At a follow-up examination over 2 years later, the
      patients were free of symptoms and the findings of a neurological examination
      were normal. CONCLUSION: Two cases of myxomatous degeneration of the ligamentum
      flavum of the lumbar spine were reported, which have seldom been described as the
      cause of acute lumbar nerve root compression.

PMID- 11571662
TI  - Treatment of severe double spinal cord injuries.
AB  - This is a case report describing an injury--sustained by a 25-year-old man during
      a car accident, and characterized by fracture dislocation of the spine at the
      level of C7 and T4 accompanied by pulmonary contusion. He had an incomplete
      spinal cord lesion at the level of C7 and a complete lesion at the level of T4
      (T4 ASIA A). Imaging of the spine showed three column fractures with ventral
      spinal cord compression at both levels. Discussants of this case comment on the
      concept of acute treatment of severe double spinal cord injuries, and present
      their chosen way of management in this particular case.

PMID- 11571663
TI  - Intramedullary tuberculoma of the conus medullaris: case report and review of the
      literature.
AB  - OBJECTIVE: To illustrate the dilemmas in the diagnosis and management of
      intramedullary tuberculomas of the spinal cord. METHODS: Case report of a 32 year
      old man with tuberculous meningitis. The presence of unexplained urinary
      retention and progressive weakness in the legs led to the discovery of an
      additional tuberculoma of the conus medullaris. SETTING: Dicle University
      Diyarbakir, Turkey. RESULTS: The patient was on a 1-year course of isoniazid,
      pyrazinamide and rifampicin, and responded well to conservative treatment. Our
      patient's unique features were represented by the worsening of neurological
      symptoms while being treated with adequate anti-tuberculous medication.
      CONCLUSION: We present a case of intramedullary tuberculoma of the conus
      medullaris to illustrate the dilemmas in the diagnosis and management of this
      curable disease, and review of the literature to date.

PMID- 11571664
TI  - Prevention of fall from the bed of spinal cord injury patients.

PMID- 11571668
TI  - Rodent obesity models: an overview.
AB  - Animal obesity models differ widely in type and extent of obesity. They are
      either based on environmental factors (eg. high fat diet induced obesity),
      spontaneous mutants (i.e. ob/ob mice), genetically engineered animals (eg. mice
      with melanocortin receptor subtype-4 gene disruption (knock-out)) or mechanical
      intervention (eg. chemical lesion of the ventromedial hypothalamus). This article
      reviews available rodent models to study obesity and attempts to highlight the
      greatest utility for each model.

PMID- 11571669
TI  - Gly15Gly polymorphism within the human adipocyte-specific apM-1gene but not
      Tyr111His polymorphism is associated with higher levels of cholesterol and LDL
      cholesterol in caucasian patients with type 2 diabetes.
AB  - The recently described mutations within the human adipocyte-specific apM-1 gene
      might play a role in the pathogenesis of obesity, type 2 diabetes and related
      metabolic disorders. DESIGN: Frequency of apM-1 gene polymorphisms and their
      association with metabolic parameters was evaluated in a population-based sample
      of 556 type 2 (316 males / 240 females) diabetic patients. PCR-based RFLP
      analysis was performed in blood samples. The T --> G transition at nucleotide +45
      within exon-2 [Gly15Gly] was detected with an allelic frequency of 0.91 for the
      wildtype allele and 0.09 for the mutated allele. The missense point mutation (TAC
      --> CAC) at nucleotide +331 within exon 3 [Tyr111His] was detected with an
      allelic frequency of 0.97 and 0.03, respectively. These frequencies did not
      differ from a non-diabetic cohort examined earlier. Concerning the Gly15Gly
      polymorphism, the TT-genotype was found in 457 (82.2%) and the TG-genotype in 99
      (17.8%), concerning the Tyr111His polymorphism, TT-genotype was found in 525
      (94.4) and TC-genotype in 31 (5.6%) of type 2 diabetic patients. In TG-genotype
      as compared to TT-genotype significantly more patients had LDL-serum levels in
      high LDL-classes (<150 mg/dl: 24.4% (TG) vs. 41.4% (TT), 150mg/dl to 190mg/dl:
      40.0% (TG) vs. 33.9% (TT), >190 mg/l: 35.6% (TG) vs. 25.0% (TT); p = 0.010). No
      differences in serum levels of lipids were found in genotype-subgroups of the
      Tyr111His polymorphism. Thus, Gly15Gly polymorphism of apM-1 gene might play a
      role in dyslipidaemia in type 2 diabetic patients.

PMID- 11571670
TI  - Undiagnosed diabetes mellitus and metabolic control assessed by HbA(1c) among
      residents of nursing homes.
AB  - AIMS/HYPOTHESIS: Diabetes prevalence and diabetes care in residents of nursing
      homes is a neglected area of research although the growing number of elderly
      people with diabetes represents a growing challenge for health care in most
      countries. In this study, we used HbA(1c) measurement to estimate the percentage
      of residents with undiagnosed diabetes and the quality of metabolic control of
      subjects with known diabetes in nursing homes. METHODS: All 41 nursing homes in
      the county of Heinsberg in Northrhine-Westfalia were asked to complete a
      structured questionnaire on the prevalence of known diabetes among all residents.
      In addition, all residents were offered measurement of glycated haemoglobin A1c
      (HbA(1c)) from a capillary blood sample. Undiagnosed diabetes was defined by a
      HbA(1c) level greater than 6.0%. RESULTS: 39 nursing homes participated in the
      study comprising 99.6% of all residents. Among the 1936 residents 507 (26.2%)
      were known to suffer from diabetes. Among the latter 37.0% were under insulin
      treatment. Blood samples for the determination of HbA(1c) were obtained from 979
      subjects from 20 nursing homes. Among those 60 years old or above (n = 843) the
      mean level of HbA(1c) in those with known diabetes was 7.3 +/- 1.5% and in those
      without 6.1 +/- 0.9%. Only 16.7% of the subjects with known diabetes had a
      HbA(1c) greater than 8.5% indicating poor metabolic control. Among the residents
      previously not known to have diabetes 47.2% had a HbA(1c) equal to or greater
      than 6.1%, but among those only 8.5% had a HbA(1c) greater than 7.0%.
      CONCLUSIONS/INTERPRETATION: Although the prevalence of undiagnosed diabetes
      mellitus defined by HbA(1c) above the normal range in elderly nursing home
      residents is high, only few may require treatment. The quality of metabolic
      control among those with known diabetes mellitus is better than expected.

PMID- 11571671
TI  - Efficacy of benfotiamine versus thiamine on function and glycation products of
      peripheral nerves in diabetic rats.
AB  - In rats with streptozotocin (STZ) induced diabetes the effect of (watersoluble)
      thiamine nitrate and of (lipidsoluble) benfotiamine on peripheral nerve function
      (motor nerve conduction velocity) as well as on the formation of advanced
      glycation end-products in peripheral nerve tissue was studied. In one group of
      animals drug administration was started immediately after diabetes induction
      (prevention study) and in another group two months after diabetes induction
      (treatment study). Motor nerve conduction velocity (NCV) dropped by 10.5% in
      diabetic animals, carboxymethyl-lysine (CML) rose to a 3.5fold concentration,
      deoxyglucosone (3DG)-type AGE formation was increased 5.1fold compared with
      controls. After three months preventive administration of both vitamin B(1)
      preparations NCV had increased substantially compared with results in diabetic
      controls. It was nearly normal after six months with benfotiamine, while the
      administration of thiamine nitrate resulted in no further amelioration. NCV was
      nearly normalized after six months of benfotiamine application but not with
      thiamine. Furthermore, benfotiamine induced a major inhibition of neural
      imidazole-type AGE formation and completely prevented diabetes induced
      glycoxidation products (CML). Treatment with thiamine did not significantly
      affect AGE or cmL levels. Unlike treatment with water-soluble thiamine nitrate
      timely administration of liposoluble prodrug benfotiamine was effective in the
      prevention of functional damage and of AGE and cmL formation in nerves of
      diabetic rats.

PMID- 11571672
TI  - Obesity in Austria: body mass index of 15 000 euthyroid men and women referred to
      a thyroid outpatient service between 1992 and 2000.
AB  - A mean body mass index (BMI) of 25.4 +/- 5.0 kg/m(2) was calculated in 15439
      euthyroid patients newly referred to our thyroid outpatient department from
      January 1, 1992 until December 31, 1999. This patient population included 2916
      men aged 50 +/- 16 years (BMI: 26.2 +/- 4.3 kg/m(2)) and 12563 women aged 47 +/-
      17 years (BMI 25.3 +/- 5.1 kg/m(2) ). Mean BMI appeared to rise (p < 0.01) from
      25.0 +/- 4.7 kg/m(2) (1992) to 25.6 +/- 5.0 kg/m(2) (1999) and the share of obese
      patients (BMI > 30 kg/m(2)) increased from 13.8% in 1992 to 17.2% in 1999.
      However these changes were parallelled by a rise (p < 0.01) in the mean age of
      newly referred patients from 45 +/- 16 years (1992) to 49 +/- 17 years (1999).
      When the whole population was subdivided into groups of different age no time
      related trend was apparent in mean BMI or in the prevalence of obesity in any of
      these subgroups. Only in men and women beyond 60 years of age BMI of those
      referred in 1998 and 1999 was higher (p < 0.05) than in those individuals
      referred in 1992-1994. These data indicate that close to half of all euthyroid
      patients referred to a thyroid outpatient service in eastern Austria is
      overweight. From 1992 to the end of 1999 there was, however, no marked increase
      in the prevalence of obesity in this population.

PMID- 11571673
TI  - Estrogenic status influences nitric oxide-regulated TNF-alpha release from human
      peripheral blood monocytes.
AB  - Cytokines and nitric oxide (NO) have been implicated in bone loss caused by
      estrogen deficiency. Here we evaluated the effect of nitric oxide synthase (NOS)
      inhibitors on the bone particle resorbing activity and TNF-alpha release of
      cultured peripheral blood monocytes (PBM) obtained from 10 premenopausal (PreM)
      and 10 postmenopausal (PostM) women. Gonadal status (menopause < 3 yr) was
      assessed by FSH and estradiol. Bone alkaline phosphatase and N-Telopeptide were
      significantly increased in PostM. Significant differences between PreM and PostM
      women were observed in bone mineral density of lumbar spine. The bone particle
      resorbing activity of PBM cultured in the presence of L-arginine-methyl ester
      (NAME) or aminoguanidine, NOS inhibitors, was determined by (45)Ca release from
      rat bone labeled particles. TNF-alpha release was assayed in supernatants by
      ELISA. (45)Ca release was higher in PostM (p < 0.01) and was enhanced by NAME (p
      < 0.02). Furthermore, TNF-alpha release from PBM was significantly higher in
      PostM (p < 0.01). Aminoguanidine significantly increased TNF-alpha release in
      PreM. Based on these findings and on the evidence that estrogen stimulates NOS,
      we suggest that estrogen withdrawal may reduce the inhibitory effect of NO on TNF
      alpha release. Thus, this increased production of TNF-alpha could contribute to
      the increased postmenopausal bone turnover.

PMID- 11571674
TI  - Peripheral levels of vascular endothelial growth factor (VEGF) are higher in
      gonadotropin stimulated as compared to natural ovarian cycles.
AB  - The purpose of the present study was to investigate the stability of vascular
      endothelial growth factor (VEGF) in plasma samples and the influence of ovarian
      hyperstimulation on systemic levels of VEGF. Stability assays for VEGF in plasma
      samples revealed significant increases following even short incubations of
      samples at room temperature (< or = 2 h, p < 0.001). To investigate a possible
      impact of controlled ovarian hyperstimulation (COH) on peripheral VEGF levels,
      serial blood collection over one menstrual cycle was performed in unstimulated as
      well as in gonadotropin-stimulated cycles for in vitro fertilisation/embryo
      transfer (IVF/ET) (10 women each). Peripheral levels for VEGF were significantly
      higher in gonadotropin stimulated cycles as compared to non-stimulated cycles (p
      < 0.001). There was no significant difference between follicular phase and luteal
      phase levels in either group. VEGF levels tended to correlate with the number of
      follicles detected by vaginal sonography prior to oocyte aspiration (p = 0.051).
      In conclusion, VEGF levels are elevated in gonadotropin-stimulated IVF/ET cycles
      as compared to natural cycles.

PMID- 11571675
TI  - Rapid increase in bone mineral density in a child with osteoporosis and
      autoimmune hypoparathyroidism treated with PTH 1-34.
AB  - We describe a 16-year-old girl with autoimmune polyglandular syndrome type 1
      including hypoparathyroidism, who had osteoporosis that improved rapidly with
      parathyroid hormone replacement therapy. Patients with hypoparathyroidism usually
      have high bone mass. Our patient developed vertebral compression fractures at age
      10, shortly after hypoparathyroidism was diagnosed. She continued to have low
      lumbar bone mass until age 16, when a dual energy x-ray absorptiometry (DEXA)
      revealed a Z score of - 2.2 SD. Several factors including decreased physical
      activity, total body magnesium depletion, and intermittent ketoconazole and short
      term prednisone treatment, may have contributed to the development and
      progression of osteoporosis. Therapy with synthetic human parathyroid hormone
      (PTH) 1-34 rapidly normalized lumbar bone mass, as assessed by DEXA.

PMID- 11571676
TI  - Endoscopic ultrasonography (EUS) and fine-needle aspiration (FNA) cytology for
      diagnosis of chronic pancreatitis.
AB  - BACKGROUND AND STUDY AIMS: Previous studies have shown that endoscopic
      ultrasonography (EUS) sensitively detects morphologic abnormalities due to
      chronic pancreatitis. However, morphologic EUS findings have limited specificity,
      particularly at the early stages of chronic pancreatitis. Our aims were to study
      pancreatic morphology and inflammation in patients with chronic pancreatitis,
      using EUS and fine-needle aspiration cytology (EUS-FNA), and to compare the
      results with those of endoscopic retrograde cholangiopancreatography (ERCP) and
      pancreatic function tests. PATIENTS AND METHODS: 37 patients (48 +/- 13 years)
      with clinical symptoms and laboratory test findings suggestive of chronic
      pancreatitis were prospectively studied. Patients with malignancy or major
      concomitant disorders were excluded. Clinical evaluation included indirect
      pancreatic function tests. Morphologic criteria for chronic pancreatitis included
      echo-intense septae/echo-reduced foci (i. e. pseudolobularity), ductal
      irregularities, and calcifications. EUS-FNA was performed in 27/37 patients, by
      means of the Hitachi FG34-UX echo endoscope and a 22-gauge needle, and tissue
      specimens were submitted for standard cytological evaluation. ERCP served as
      reference in all patients, using the Cambridge classification. RESULTS: 31
      patients had chronic pancreatitis while six had normal findings at ERCP. EUS
      showed morphologic abnormalities of the pancreas in 33 patients. Morphologic
      abnormalities alone reached a sensitivity of 97 % for chronic pancreatitis with a
      specificity of only 60 %, while the positive predictive value (PPV) was 94 %, and
      the negative predictive value (NPV) was 75 %. EUS-FNA increased the negative
      predictive value to 100 % and the specificity to 67 %. On average, 2.3 needle
      passes were necessary to obtain sufficient amounts of tissue. The correlation of
      EUS findings with pancreatic function tests was poor. EUS results were in
      agreement with regard to the severity of chronic pancreatitis in 5/8 patients
      with grade I disease, in 11/13 patients with grade II, and in 10/10 patients with
      grade III disease. Minor complications occurred in two patients (7 %).
      CONCLUSIONS: EUS is as sensitive and effective as ERCP in the detection of
      chronic pancreatitis, particularly when only mild disease is present. However,
      EUS findings have limited specificity, particularly in patients with mild
      disease. EUS-FNA with cytology is safe and improves the negative predictive
      value. Negative EUS-FNA findings rule out chronic pancreatitis, but cytological
      investigation alone does not improve the specificity of EUS findings, suggesting
      that further improvements in tissue sampling and analysis are necessary to
      support routine use of FNA in patients with chronic pancreatitis.

PMID- 11571677
TI  - Impact of miniprobes compared to conventional endosonography in the staging of
      low-grade gastric malt lymphoma.
AB  - BACKGROUND AND STUDY AIMS: In patients with low-grade gastric MALT lymphoma,
      conventional endoscopic ultrasonography (EUS) is considered to be the most
      accurate modality for locoregional staging. The aim of this study was to evaluate
      the diagnostic role of ultrasonic miniprobes as part of routine clinical staging.
      PATIENTS AND METHODS: A total of 39 patients who were histologically diagnosed
      with low-grade MALT lymphoma were reviewed retrospectively before treatment (n =
      15) and during follow-up (n = 24). Assessment of tumor penetration into the
      gastric wall was based on the TNM system. Pathological lymph-node involvement was
      suggested by the presence of inhomogeneous hypoechoic echo patterns, with clearly
      demarcated borders. All examinations were carried out using a mechanical
      miniprobe (Olympus; diameter 2.4 mm, 12 MHz) introduced through the working
      channel of the endoscope. Ultrasonic miniprobe findings were compared with
      conventional EUS data and histology. RESULTS: Using pretreatment endoscopic
      ultrasonography, gastric lymphomas presented endoscopically with an ulcer (in
      five of 15 patients) or a diffuse infiltrative pattern (ten of 15 patients). The
      ultrasonic miniprobe identified a T1 lesion in 53 % (T2, 33 %) and EUS in 60 %
      (T2, 20 %) of cases. Pathological lymph-node involvement in T1-T2 lesions was
      diagnosed with the ultrasonic miniprobe in 53 % of cases and with EUS in 60 %.
      Using endoscopic ultrasonography during the follow-up period, in patients with
      normal miniprobe ultrasonography (n = 15), the histological examination confirmed
      a complete remission in all patients. Hypoechoic thickening of the mucosa or
      submucosa, or both, was seen in nine patients. Endoscopic biopsies in four of
      these nine patients revealed recurrent lymphoma. CONCLUSIONS: The ultrasonic
      miniprobe can be recommended as part of routine care in patients with gastric
      MALT lymphoma, both initially and during the follow-up period. The clinical
      significance of ultrasonic miniprobe examinations is that they can be performed
      as a single-step procedure during diagnostic endoscopy.

PMID- 11571679
TI  - Fixation of a modified covered esophageal stent: its clinical usefulness for
      preventing stent migration.
AB  - BACKGROUND AND STUDY AIMS: Membrane-covered self-expandable metal stents are
      effective in preventing tumor ingrowth and stent obstruction in patients with
      inoperable esophageal cancer, but migration of stents continues to be a major
      problem. We therefore constructed a modified covered self-expandable esophageal
      metal stent capable of being fixed using a silk thread. The stent was studied
      prospectively to define its palliative characteristics and whether it is
      effective in preventing migration. PATIENTS AND METHODS: Modified covered self
      expandable metal stents were placed in 17 patients with malignant gastric cardiac
      cancer involving the esophagogastric junction, 41 patients with esophageal
      cancer, and three patients with tracheoesophageal fistulas. Clinical and
      radiographic follow-up examinations were carried out at regular intervals.
      RESULTS: Placement of the stent was successful in all patients, with good
      symptomatic relief and no serious stent-related complications such as esophageal
      perforation or hemorrhage. Acute stent placement problems, such as incomplete
      expansion or acute angulation of the stent, were noted in four patients. However,
      during a mean follow-up period of 7.5 months (range 1 to 17 months), there was no
      stent migration. CONCLUSIONS: Modified covered self-expandable esophageal metal
      stents of this type would be very effective in preventing stent migration,
      especially in patients with malignant gastric cardiac cancer extending to the
      lower esophagus, those with short-segment esophageal cancer, and those with
      tracheoesophageal fistulas.

PMID- 11571678
TI  - Self-expanding coil stent with a long delivery system for palliation of
      unresectable malignant gastric outlet obstruction: a prospective study.
AB  - BACKGROUND AND STUDY AIMS: Peroral intubation of a self-expanding metal stent is
      usually difficult in patients with unresectable malignant gastric outlet
      obstruction, because the delivery systems currently available are not long enough
      and cannot easily pass the angulated gastroduodenal structure. We carried out a
      prospective study to assess the efficacy of a coil stent with a newly developed
      long delivery system, for palliation of unresectable malignant gastric outlet
      obstruction. PATIENTS AND METHODS: In 29 patients with unresectable malignant
      gastric outlet obstruction, caused by gastric cancer (26 patients), pancreatic
      head cancer (two patients), or duodenal cancer (one patient), peroral intubation
      of a self-expanding nickel-titanium coil stent was attempted, using a lengthened
      delivery system of 150 cm, under endoscopic and fluoroscopic guidance. RESULTS:
      Management was successful in 26 of 29 patients (89.7 %) without immediate major
      complications. In one patient in whom peroral intubation failed, percutaneous
      intubation of the coil stent via percutaneous endoscopic gastrostomy was done.
      After insertion of the coil stent, food ingestion with symptomatic improvement
      with regard to vomiting was achieved in 26 of 27 patients (96.3 %), including the
      patient with percutaneous stent insertion. During the follow-up period, dysphagia
      and Karnofsky scores improved significantly. Stent migration occurred in two
      patients, and tumor ingrowth in another two; re-intervention was done
      successfully performed in two instances. The mean survival time was 124 days
      (range 34 - 310 days) in the 22 patients who had no need for re-intervention
      during follow-up; among these was a patient who experienced stent occlusion by
      food material, which was easily corrected with endoscopic flushing. CONCLUSIONS:
      Peroral intubation of a self-expanding coil stent using a long delivery system is
      a safe and effective palliative technique for unresectable malignant gastric
      outlet obstruction, and significantly improves the quality of life of patients.

PMID- 11571680
TI  - Detection of human gastric cancer in resected specimens using a novel infrared
      fluorescent anti-human carcinoembryonic antigen antibody with an infrared
      fluorescence endoscope in vitro.
AB  - BACKGROUND AND STUDY AIMS: An indocyanine green derivative (ICG-sulfo-OSu) that
      can be used as an infrared fluorescent labeling substance suitable for detecting
      microlesions with an infrared fluorescence endoscope has been developed. The aims
      of the present study were to develop an infrared fluorescence endoscope and to
      demonstrate its usefulness in detecting cancerous tissue using an antibody
      coupled with ICG-sulfo-OSu. MATERIALS AND METHODS: ICG-sulfo-OSu-labeled mouse
      anti-human carcinoembryonic antigen (CEA) antibody and an infrared fluorescence
      endoscope were used in this study. Biopsy specimens of gastric cancer were
      stained with anti-CEA antibody using the avidin-biotinylated peroxidase complex
      method. The positive specimens used for the infrared imaging analysis were
      freshly resected stomachs from three patients. RESULTS: Treatment of freshly
      resected stomach specimens with ICG-sulfo-OSu-labeled-anti-CEA antibody complex
      resulted in positive staining of the tumor sites on infrared fluorescence
      endoscopy, and the infrared fluorescent images correlated well with the tumor
      sites. CONCLUSIONS: An anti-CEA antibody with affinity for cancerous lesions and
      labeled with ICG-sulfo-OSu can therefore be imaged using this infrared
      fluorescence endoscope. Specific antibodies tagged with ICG-sulfo-OSu can label
      cancer cells and can generate a strong enough fluorescent signal to detect small
      cancers when examined with an infrared fluorescence endoscope.

PMID- 11571681
TI  - Endoscopic snare excision of large pedunculated colorectal polyps: a new, safe,
      and effective technique.
AB  - BACKGROUND AND STUDY AIMS: The endoscopic polypectomy of large pedunculated
      polyps can have serious complications, such as hemorrhage, which has an incidence
      of about 2 %. We describe here a new, safe, and effective technique of endoscopic
      polypectomy for the treatment of large pedunculated colorectal polyps using a
      standard detachable diathermic snare. PATIENTS AND METHODS: 35 patients (18 men,
      12 women; mean age 67.3, range 35 - 82), with 43 pedunculated colorectal polyps,
      of benign appearance and of size 3 cm or larger (range 3 - 5 cm) on colonoscopy,
      were included in our study. The polypectomy was performed in two steps: a) we
      first placed a polypectomy snare round the middle of the stalk, as a prophylactic
      measure to prevent postpolypectomy bleeding, and we then took out the colonoscope
      without removing the snare after dismantling it and blocking with a clip; b)
      endoscopic polypectomy was done using a second polypectomy snare, and transecting
      the stalk of the polyps at 2 mm above the first snare. The first polypectomy
      snare was left in place, and the patients were discharged within 3 hours of
      endoscopic polypectomy. The first polypectomy snare sloughed off spontaneously
      and slipped down the anus, being evacuated within 4 days following the endoscopic
      polypectomy. RESULTS: The ensnared polyps were located in the rectosigmoid region
      (n = 27), and the descending (n = 13) and transverse colon (n = 3). Complete
      ensnarement of the head of the polyp with a single endoscopic treatment was
      obtained in all cases. In addition, no procedural or delayed bleeding was noted
      during a 6-month follow-up. CONCLUSIONS: Our technique allows us to overcome the
      risk of bleeding, since the use of a standard diathermic snare makes it easier to
      obtain optimal tightness. Moreover, this technique is cheaper than the use of the
      standard detachable snare currently available (the cost of the snares being
      $50.52 compared with $189.47).

PMID- 11571682
TI  - Effectiveness of endoscopic treatment modalities in complicated hepatic hydatid
      disease after surgical intervention.
AB  - BACKGROUND AND STUDY AIMS: Hepatic hydatid cyst is a common disease in Turkey and
      the rupture of the cyst into the biliary tract is the most common complication
      which is difficult to detect and to manage. The aim of this study was to
      investigate the effectiveness of endoscopic treatment modalities in hydatid cyst
      patients with biliary complications who had previously undergone surgery.
      PATIENTS AND METHODS: Over the last 8 years, by means of endoscopic retrograde
      cholangiopancreatography (ERCP), we have examined 87 patients with postoperative
      biliary symptoms who had previously undergone surgery for hepatic hydatid disease
      of the liver. Endoscopic treatment modalities were as follows: endoscopic
      sphincterotomy (ES) and nasobiliary drainage in patients with biliary fistula;
      balloon and or bougie dilation and stenting in patients with biliary stricture;
      and ES and balloon extraction in patients with residual hydatid material within
      the bile duct. RESULTS: Findings from ERCP included biliary fistula in 55
      patients (63.2 %), biliary stricture in 16 (18.4 %), and residual hydatid
      material within the bile duct in 14 (16.1 %). Two patients had normal findings on
      ERCP. In total, 85 patients were treated by means of endoscopic modalities. The
      time to closure of fistula was 17.8 +/- 5 days and the rate of fistula closure
      was 81 %. Biliary stenting was performed in 13 patients with biliary stricture.
      Endoscopic removal of hydatid material was achieved in 14 patients. The overall
      success rate of endoscopic treatment was 86 %, and a second surgical intervention
      was required only in six patients. No serious complication was encountered after
      endoscopic procedures. CONCLUSIONS: Endoscopic treatment modalities are safe and
      helpful methods for the treatment of biliary complications of hepatic hydatid
      cyst in the postoperative period.

PMID- 11571683
TI  - Cleaning and disinfection practices in digestive endoscopy in spain: results of a
      national survey.
AB  - BACKGROUND AND STUDY AIMS: Disinfection and surveillance of it are important for
      ensuring safety in gastrointestinal endoscopy. The aim of this survey was to
      assess the current status of disinfection in gastrointestinal endoscopy units in
      Spain. MATERIALS AND METHODS: An anonymous questionnaire on cleaning and
      disinfection methods was sent to gastrointestinal endoscopy units at 244 public
      hospitals in Spain. A minimum standard of disinfection (MSD) was defined to
      evaluate the appropriateness of disinfection practices. RESULTS: A total of 144
      centers responded (58 %). All units perform manual washing of endoscopes before
      disinfection. Automatic washers are available in only 23 % of the centers.
      Selective cleaning of internal channels is systematically performed in 85 % of
      the centers. Glutaraldehyde-based disinfectants are the most commonly employed
      (84 % of units). The time of exposure to the disinfectant is at least 10 min in
      97 % of units, but 20 min or more in only 36 % of them. Endoscopic accessories
      are sterilized in 57 % of centers. The MSD was complied with by 79 % of the units
      evaluated. Compliance with the MSD was significantly lower in small units (P =
      0.0005) performing small numbers of examinations per month. Quality control tests
      on the efficacy of disinfection methods are conducted at 66 % of the centers.
      Specialized personnel record disinfection procedures in 85 % of the centers and
      supervise them in 55 % of the centers. Half of the units have inadequate
      equipment and facilities. CONCLUSIONS: This survey suggests that cleaning and
      disinfection practices in gastrointestinal endoscopy units in Spain have improved
      in recent years, and that there is a good compliance with standard guidelines.
      Most units should improve their equipment and facilities in order to provide
      better comfort and safety for patients and staff.

PMID- 11571684
TI  - Hemodynamic analysis of esophageal varices using color Doppler endoscopic
      ultrasonography to predict recurrence after endoscopic treatment.
AB  - BACKGROUND AND STUDY AIMS: The time to recurrence of esophageal varices may vary
      greatly between patients even after the same endoscopic therapy. To clarify the
      factors which contribute to recurrence after endoscopic treatment, the
      hemodynamics and morphology of the left gastric vein (LGV) were investigated
      using color Doppler endoscopic ultrasonography (EUS). PATIENTS AND METHODS: A
      total of 31 patients with high-risk esophageal varices underwent color Doppler
      EUS before receiving endoscopic variceal ligation and endoscopic injection
      sclerotherapy combined therapy. Endoscopic examination was performed every 3
      months after the treatment to evaluate recurrence of varices. RESULTS: A total of
      18 patients responded to the therapy, while 13 patients did not respond, and had
      recurrence within 12 months. The hepatofugal flow velocity in the LGV trunk was
      significantly lower in the responders (9.9 vs. 13.9 cm/sec; P = 0.02). The branch
      pattern of the LGV was categorized into three groups: anterior branch dominant,
      posterior branch dominant, and no-dominant type. The incidence of the anterior
      branch dominant type was significantly less in responders (17 vs. 70 %; P =
      0.01). There was no significant difference in the LGV trunk diameter and the size
      of the paraesophageal vein between the two groups. CONCLUSION: Risk factors for
      recurrence can be analyzed in detail using color Doppler-EUS. Further
      investigation using color Doppler-EUS may enable us to select the optimal way to
      treat esophageal varices to prevent recurrence.

PMID- 11571685
TI  - Low power diode laser treatment using indocyanine green for eradication of
      esophageal varices.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic variceal ligation (EVL) is an alternative
      to sclerotherapy for the treatment of esophageal varices, but is associated with
      higher rates of recurrence and subsequent bleeding than sclerotherapy. To prevent
      recurrence of varices after EVL, we have developed a low-dose diode laser therapy
      combined with the injection of indocyanine green, which allows enhanced tissue
      absorption of the laser beam selectively around varices. In this study we
      investigated the efficacy and safety of this technique. PATIENTS AND METHODS:
      Eight patients with F2 or F3 esophageal varices were enrolled. At 1 week after
      EVL, indocyanine green solution (1 mg/ml) was injected submucosally around the
      remaining varices. A diode laser (power 10 watts) was applied to the surface from
      the esophagogastric junction to 5 cm above it. The spot size was kept to 5 mm in
      diameter. RESULTS: Laser irradiation was performed safely, without bleeding from
      the varices, or perforation. There were no major complications. Endoscopy 1 month
      later showed F0 forms in seven patients, F1 in one patient, and no red color sign
      in any patient. No recurrence of varices has been observed in any of the patients
      during the follow-up period of at least 12 months. CONCLUSION: This technique may
      provide a simple, safe and effective procedure, as an additional treatment to
      EVL, for the prevention of recurrence of esophageal varices.

PMID- 11571686
TI  - Malignant gastric outlet obstruction: is stenting the standard?

PMID- 11571687
TI  - Part 1. The Erlanger endo-trainer.

PMID- 11571688
TI  - A 0.8-mm depressed adenoma of the colon with high-grade dysplasia.
AB  - Flat and depressed cancers of the colon have now been recognized in several
      centers throughout the world. We report here a case of a 0.8-mm depressed adenoma
      with high-grade dysplasia in a 70-year-old man. We believe this to be the
      smallest adenoma ever reported, and unusually (for a small lesion) it was
      positive for the K-ras mutation.

PMID- 11571689
TI  - Successful treatment of Boerhaave's syndrome with endoscopic insertion of a self
      expandable metallic stent: report of three cases and a review of the literature.
AB  - Boerhaave's syndrome is a rare but life-threatening condition which presents a
      diagnostic as well as therapeutic challenge. Early diagnosis and prompt surgical
      repair are critical for survival; however late recognition of esophageal rupture
      is not unusual. A variety of nonsurgical approaches have been proposed,
      particularly in the case of delayed diagnosis. In recent years, the insertion of
      a metallic stent has been described as a promising modality in the treatment of
      spontaneous esophageal rupture. We report three cases of Boerhaave's syndrome
      treated with self-expandable metallic stents and review previously published
      cases.

PMID- 11571690
TI  - Endoscopic ultrasound-guided bilioduodenal anastomosis: a new technique for
      biliary drainage.
AB  - Endoscopic biliary stenting is the most common method of treating obstructive
      jaundice. We present a new technique of biliary drainage using endoscopic
      ultrasound (EUS) and EUS-guided puncture of the common bile duct (CBD). A 56-year
      old man with obstructive jaundice was referred for EUS and endoscopic retrograde
      cholangiopancreatography (ERCP) because a computed tomography (CT) scan had shown
      a pancreatic mass in the head of the pancreas and a dilated CBD. The patient was
      enrolled in a preoperative chemoradiotherapy protocol and biliary stenting was
      required. Deep cannulation was not obtained even after a precut and the procedure
      was stopped. Using a therapeutic EUS scope (FG 38X Pentax), the CBD was punctured
      with a 5-F needle-knife under EUS guidance and a cholangiogram was obtained. A
      0.35-inch guide wire was introduced into the CBD. The EUS scope was removed and a
      duodenoscope was introduced, allowing the placement through the duodenum of a 10
      F plastic stent. The CBD was drained properly. No complication occurred.

PMID- 11571691
TI  - Black esophagus: an unusual finding during routine endoscopy.

PMID- 11571692
TI  - Esophageal impaction: a rare complication of tissue glue injection for gastric
      variceal bleeding.

PMID- 11571693
TI  - Diagnosis of a pleural mesothelioma by endosonography-guided transgastric fine
      needle aspiration.

PMID- 11571694
TI  - Giant stone in the common bile duct.

PMID- 11571697
TI  - Cerebrospinal fluid markers in children with cerebral white matter abnormalities.
AB  - Disorders of the cerebral white matter in children constitute a heterogeneous
      group and the diagnostic work is often complicated. Clinical and radiological
      characteristics can provide diagnostic clues but there is a need for further
      diagnostic methods. This study focused on assessing neurochemical "markers" in
      the cerebrospinal fluid considered to reflect damage to white matter components
      such as myelin and glial cells as well as neurones with their axons and synapses.
      The aim was to evaluate whether they contributed to the elucidation of pathogenic
      processes and the direction of further diagnostic efforts. Seventeen of the 26
      cases had increased levels of the glial cell marker ganglioside GD3, indicating
      gliosis, or of the CNS myelin marker sulfatide, indicating myelin disturbance. As
      signs of disturbed maturation or sustenance, the nerve cell markers GD1 b, GT1 b
      and total gangliosides were reduced, as was the synapse marker GD1a. Increased 5
      HIAA indicated increased serotonergic turnover. Children with an increased level
      of the axonal marker Tau protein had a progressive disease whereas GD1a was
      reduced in the progressive group (n = 11). In contrast, GD3 and HVA were
      increased in the non-progressive group (n = 15). The chemical profiles were found
      to be useful, in combination with clinical and radiological findings, when
      investigating children with white matter abnormalities.

PMID- 11571696
TI  - Reduction of carotid artery blood flow in pediatric patients with syncope:
      evaluation with head-up tilt test.
AB  - We investigated the effect of postural changes on cerebral circulation by
      measuring carotid artery blood flow (CABF) in the supine position and during head
      up tilt (HUT) test using a Doppler flow meter. Subjects included 10 patients with
      neurally mediated syncope, 10 patients with orthostatic intolerance, 8 with
      epilepsy, aged between 8 to 24 years (mean +/- SD, 13.9 +/- 4.1 years). The test
      caused pallor and dizziness in 16 patients (symptomatic), while no symptoms were
      recognized in the other 12 patients (asymptomatic). Significant reductions in the
      mean CABF (Fm), maximum CABF (Fs) and minimum CABF (Fd), components of the CABF
      waveform, were noticed during HUT compared to before HUT (supine), and these
      reductions in symptomatic patients were more severe than those in asymptomatic
      patients (Fm: - 2.8 +/- 2.0 SD vs - 0.7 +/- 1.4 SD; Fs: - 2.7 +/- 1.5 SD vs - 0.9
      +/- 1.3 SD; Fd: - 4.5 +/- 2.8 SD vs - 2.2 +/- 2.1 SD). Reductions in Fm, Fs and
      Fd in the symptomatic patients during HUT lasted longer than those of the
      asymptomatic patients, being statistically significant for Fm and Fs (Fm: p <
      0.01; Fs: p < 0.05). The criteria during HUT for distinguishing neurally mediated
      syncope (NMS) from others was Fs: < - 4 SD and Fd: < - 5 SD. Our data suggest
      that reduction of CABF should be carefully evaluated for the diagnosis of
      neurally mediated syncope in pediatric patients. Such a reduction might be an
      essential mechanism of syncopal attacks.

PMID- 11571698
TI  - Infantile presentation of the mtDNA A3243G tRNA(Leu (UUR)) mutation.
AB  - Mitochondrial DNA (mtDNA) disorders are clinically very heterogeneous, ranging
      from single organ involvement to severe multisystem disease. One of the most
      frequently observed mtDNA mutations is the A-to-G transition at position 3243 of
      the tRNA(Leu (UUR)) gene. This mutation is often related to MELAS syndrome.
      However, not all patients with the A3243G mutation share the same clinical
      disease expression and, on the contrary, patients clinically exhibiting MELAS
      syndrome may have other mtDNA mutations. Here we describe two patients with a
      very early infantile presentation of disease associated with the A3243G mutation.
      Patient 1 presented with hypotonia, feeding difficulties and failure to thrive
      (FTT) at the age of 3 months. Laboratory investigations showed persistent
      hyperlactic acidemia, elevated lactate/pyruvate ratios and elevated alanine
      concentrations in blood. Developmental delay was progressive and he developed
      cardiomyopathy and seizures. Death occurred at the age of 3.5 years. Patient 2
      was born prematurely and had persistent, severe lactic acidosis from birth on.
      Moderate biventricular hypertrophy was seen on ultrasound studies of the heart
      and, suffering from progressive lactic acidosis, he died at the age of 13 days.
      Because of the rarity of this very early presentation, we searched the literature
      for other infantile cases associated with the A3243G mutation and found 8
      additional ones. In infants presenting with lactic acidosis/hyperlactic acidemia,
      failure to thrive, hypotonia, seizures and/or cardiomyopathy, mtDNA mutational
      analysis, also for the disease entities, usually only observed in juveniles or
      adults is warranted.

PMID- 11571699
TI  - Phenotypic heterogeneity and adverse effects of serine treatment in 3
      phosphoglycerate dehydrogenase deficiency: report on two siblings.
AB  - Clinical experience with the treatment of 3-phosphoglycerate dehydrogenase
      deficiency, a rare inherited disorder of serine synthesis, is scarce. We report
      on two sisters with phenotypic heterogeneity and a favourable response to
      combined serine and glycine supplementation. The elder sibling was found to be
      normocephalic at birth and showed moderate delay of white matter myelinisation,
      while her seizures arrested spontaneously even without treatment. In the younger
      sister with the classical phenotype, feeding difficulties with recurrent gastro
      oesophageal reflux prompted us to treat her temporarily with high-dose serine
      (1400 mg/kg/day). An arrest of head growth then occurred but could be reversed by
      reducing the serine supply. In both children serine therapy was associated with
      decreased concentrations of methionine, isoleucine, and ornithine in the
      cerebrospinal fluid, attributed to competitive inhibition of neutral amino acid
      transport across the blood-brain barrier. In contrast to reports in the
      literature, these findings demonstrate that congenital microcephaly, intractable
      seizures, and dysmyelinisation are not invariably present in patients with 3
      phosphoglycerate dehydrogenase deficiency. An adverse effect of high-dose serine
      therapy on head growth and on the transport of neutral amino acids across the
      blood-brain barrier should be considered and requires adjustment of treatment.

PMID- 11571700
TI  - Reducing body myopathy with cytoplasmic bodies and rigid spine syndrome: a mixed
      congenital myopathy.
AB  - At the age of five years a male child started to develop a progressive rigid
      spine, torsion scoliosis, and flexion contractures of his elbows, knees, hips,
      and ankles owing to severe proximal and distal muscle weakness. He had three
      muscle biopsies from three different muscles at ages 7, 11, and 14 years,
      respectively. Myopathologically, these muscle tissues contained numerous
      inclusions which, at the ultrastructural level, turned out to be reducing bodies
      and cytoplasmic bodies, often in close spatial proximity. Similar histological
      inclusions, although not further identified by histochemistry and electron
      microscopy, were seen in his maternal grandmother's biopsied muscle tissue who
      had developed weakness of the legs and hands after the age of 50 years. The
      patient's parents were healthy, but the mother's quadriceps muscle showed an
      increased spectrum of muscle fibre diameters. Our patient, thus, had a
      neuromuscular disorder, perhaps familial, presenting as a mixed congenital
      myopathy, i.e., reducing body myopathy with cytoplasmic bodies, of which the
      morphological lesions could be consistently documented over several years in his
      different limb muscles. While other mixed congenital myopathies had shown cores
      and rods, both related to sarcomeres and thus possibly morphogenetically related,
      cytoplasmic bodies thought to be related to Z-bands and reducing bodies
      dissimilar to any muscle fibre constituent do not share any common denominator.
      Therefore, we suggest that this neuromuscular disorder may be a unique mixed
      congenital myopathy, either sporadic or genetic. In the latter case, the
      transmission pattern suggested X-linked recessive inheritance, but an autosomal
      dominant transmission with variable penetrance could not be ruled out.

PMID- 11571701
TI  - Potential role of human brain microvascular endothelial cells in the pathogenesis
      of brain abscess: inhibition of Staphylococcus aureus by activation of
      indoleamine 2,3-dioxygenase.
AB  - Cerebral abscess is a rare complication of staphylococcal septicemia in infants
      associated with high mortality and morbidity. In the pathogenesis of abscess
      formation, S. aureus, one major causative agent, interacts with endothelial cells
      of the brain vessels before reaching the central nervous system. This study
      examined the growth of S. aureus in human brain microvascular endothelial cells
      (HBMEC) cultures stimulated with cytokines. IFN-gamma inhibited S. aureus
      replication by the induction of indoleamine 2,3-dioxygenase (IDO) in HBMEC. This
      activation of IDO in HBMEC could be shown by RT-PCR and by detection of
      kynurenine in culture supernatants of activated cells. Resupplementation of L
      tryptophan abrogated the inhibitory effect of IFN-gamma on the growth of
      staphylococci, hence confirming the activation of indoleamine 2,3-dioxygenase as
      being responsible for the induced bacteriostasis. Addition of TNF-alpha enhanced
      the IFN-gamma mediated antibacterial effects, whereas TNF-alpha alone had no
      influence on staphylococcal growth. Stimulation of HBMEC with IFN-gamma failed to
      activate inducible nitric oxide synthase (iNOS) and subsequent production of
      nitric oxide (NO). Thus, intra- and extracellular depletion of L-tryptophan seems
      to be an important process in the defense against staphylococcal brain abscesses
      by means of creating an unfavorable microenvironment.

PMID- 11571702
TI  - Interferon beta-1a in children with multiple sclerosis is well tolerated.
AB  - BACKGROUND: Multiple sclerosis is a chronic demyelinating disease rare in
      children. Currently marketed disease modifying therapies are limited to adults.
      OBJECTIVE: To determine the tolerability of interferon beta-1a (IFNB-1 a) 30 mcg
      injected intramuscularly once a week in children with clinically definite
      relapsing-remitting multiple sclerosis (RRMS). DESIGN/METHODS: A standardized
      questionnaire was sent to neurologists in the United States to determine the
      tolerability of IFNB-1 a in patients younger than 16 years. RESULTS: Tolerability
      data were available for 9 of 33 children who were reported to initiate IFNB-1 a.
      Mean age on initiating treatment was 12.7 years (range 8 - 15) and mean duration
      of therapy was 17 months (range 5 - 36). No patient discontinued therapy due to
      an adverse event. CONCLUSIONS: Preliminary data indicate that weekly
      intramuscular injections of IFNB-1 a are well tolerated.

PMID- 11571703
TI  - Tumor necrosis factor-alpha gene polymorphisms in children with multiple
      sclerosis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine implicated in the
      pathogenesis of infectious and autoimmune disorders including multiple sclerosis
      (MS). Childhood-onset MS presents some clinical and laboratory features differing
      from adult disease. We studied TNF-alpha - 238 G-->A and - 308 G-->A
      polymorphisms in 24 patients with childhood-onset MS using PCR-RFLP and compared
      them with healthy control subjects from the same population (n = 93). The
      genotypes and allele frequencies were not different between patient and control
      groups (p = 0.348, 95 %CI, 0.28 - 1.92, chi(2) = 0.10 and p = 0.797, 95 %CI,
      0.312 - 2.285, chi(2) = 0.20 for - 238 and - 308 alleles, respectively). Although
      the size of the study group is small, these results do not support a role for TNF
      alpha gene polymorphisms in susceptibility to MS in children.

PMID- 11571704
TI  - Closely related Swedish Rett Syndrome females - none with MECP2 mutation
      revealed.
AB  - Mutations in the MECP2 gene are known to be associated with Rett Syndrome (RTT)
      in the large majority of sporadic cases. Four Swedish families with a total of
      eight RTT patients (two in each family), were screened and found negative for
      MECP2 mutations. The series included females with both classical and forme fruste
      phenotypes. Rett syndrome thus might still be complex and genetically
      multifactorial.

PMID- 11571705
TI  - Retrobulbar abscess in a neonate.

PMID- 11571706
TI  - Neonatal subdural and extradural haemorrhage in Prader-Willi syndrome.

PMID- 11571707
TI  - The FDA is coming! The FDA is coming!

PMID- 11571708
TI  - Commentary: minimal residual disease: how low do we go?

PMID- 11571709
TI  - Detection of bcl-2/IgH rearrangements by quantitative-competitive PCR and
      capillary electrophoresis.
AB  - BACKGROUND: PCR is the primary method for detecting minimal residual disease in
      hematologic cancers. One such gene target is the bcl-2/immunoglobulin heavy chain
      (IgH) translocation found in a majority of cases of follicular lymphoma. METHODS
      AND RESULTS: We report an accurate method for quantitative detection of the bcl
      2/IgH translocation marker of follicular lymphoma in a series of patients in
      various stages of remission and relapse who had been treated with a combination
      of ifosfamide, mitoxantrone, and etoposide (MINE) chemotherapy and monoclonal
      anti-CD20 antibody (Rituximab). The approach uses seminested PCR followed by
      analysis of the products on a fluorescent capillary electrophoresis system. The
      quantitation of bcl-2/IgH translocation-positive cells was sensitive and
      reproducible, capable of detecting as few as five malignant cells out of 300,000
      normal cells. CONCLUSION: Quantitative PCR enables one to monitor the kinetics of
      tumor reduction in patients treated with MINE chemotherapy in combination with
      Rituximab.

PMID- 11571710
TI  - Detection of clonal T-cell receptor gamma gene rearrangements using fluorescent
      based PCR and automated high-resolution capillary electrophoresis.
AB  - BACKGROUND: Analysis of T-cell receptor gamma (TCR gamma) gene rearrangements by
      PCR is a powerful tool for detecting clonal T-cell populations for the diagnosis
      of lymphoid neoplasms. We report a method for TCR gamma PCR analysis using
      capillary electrophoresis (CE). METHODS AND RESULTS: To define the threshold for
      identification of a predominant monoclonal population within a polyclonal
      background, we developed a novel objective parameter of the peak height ratio
      (Rn) of the peak of interest and the average of the two immediate flanking peaks.
      After evaluation of monoclonal, reactive, and normal T-cell populations, an Rn of
      3.0 or greater was determined to be consistent with a monoclonal population,
      whereas an Rn between 1.9 and 3.0 was considered an intermediate range. This CE
      method was compared with the standard denaturing gradient gel electrophoresis
      (DGGE) method using previously evaluated clinical specimens. Eleven of 12
      clinical specimens (92%) with a definitive diagnosis of T-cell lymphoma were
      monoclonal by CE, with 100% concordance with the DGGE method. Of nine specimens
      morphologically suspicious for T-cell lymphoma, five specimens were positive by
      CE analysis compared with four specimens by DGGE. In addition, 14 specimens for
      staging from patients with known T-cell lymphoma were studied using both the CE
      and DGGE methods, with a concordance of 86%. CONCLUSION: CE is a powerful and
      efficient method for analysis of clonality by TCR gamma PCR.

PMID- 11571711
TI  - Allelic deletion fingerprinting of urine cell sediments in bladder cancer.
AB  - BACKGROUND: Bladder cancer shows frequent nonrandom allelic deletion at various
      chromosomal regions. Genotypic detection methods could potentially identify
      patients at risk for recurrent progressive disease. In this study, we examined
      allelic deletion at specific chromosomal loci in tumor tissue and urine cell
      sediment samples using a microsatellite-based protocol. Although both allelic
      deletion and microsatellite instability have been reported in primary bladder
      cancer, microsatellite instability was not specifically examined in this study.
      We report a pilot study of 40 patients with bladder cancer in which allelic
      deletion in tumor tissue and urine cell sediment was compared with conventional
      urine cytology results. METHODS AND RESULTS: Forty tumors were analyzed using a
      set of microsatellite primers from chromosomes 3, 4, 8, 11, 14, and 17 to
      construct allelic deletion fingerprints. Cy5.5-labeled PCR products were analyzed
      using the OpenGene System and GeneObjects software. Eighty-eight percent of
      tumors showed allelic deletion. In urine cell sediments, the tumor detection rate
      was 80% compared with 50% for routine urine cytology. The allelic deletion
      fingerprinting (ADF) procedure identified 69% of incipient tumors, cases
      initially classified as normal by routine urine cytology. CONCLUSION: ADF
      analysis provides a reliable noninvasive method for the detection and monitoring
      of recurrent cancer in urine cell sediment samples from patients with bladder
      cancer.

PMID- 11571712
TI  - Commentary: molecular analysis of congenital adrenal hyperplasia in a newborn
      screening program.

PMID- 11571713
TI  - Reverse dot-blot hybridization as an improved tool for the molecular diagnosis of
      point mutations in congenital adrenal hyperplasia caused by 21-hydroxylase
      deficiency.
AB  - BACKGROUND: More than 90% of cases of congenital adrenal hyperplasia (CAH) are
      caused by mutations of the CYP21 gene that result in deficiencies of the enzyme
      21-hydroxylase. Allele-specific PCR, allele-specific oligonucleotide
      hybridization, and Southern blot analysis are the most common methods to detect
      point mutations and deletions in the CYP21 gene. METHODS AND RESULTS: This report
      is the first application of the reverse dot-blot (RDB) assay for diagnosis of the
      nine most common point mutations in the CYP21 gene associated with CAH (P30L,
      g.659A>G or g.659C>G, I172N, I236N-V237E-M239K, V281L, g.1767-1768insT, Q318X,
      R356W, P453S). Normal and mutant oligonucleotides spanning these nine mutation
      sites were spotted onto a nylon membrane. DNA was extracted from dried blood
      spots, and exons encompassing mutations from samples to be tested were amplified
      and labeled with biotin-dUTP by PCR. These exons then were hybridized to membrane
      strips. Signal detection was achieved by chemiluminescence. Thirty clinically
      confirmed cases that were identified by the Texas Newborn Screening Program were
      tested. All mutations were subsequently confirmed by automated DNA sequencing.
      CONCLUSION: The RDB method has the advantages of being accurate and cost
      effective for the molecular diagnosis of CYP21 point mutations in CAH. It permits
      simultaneous detection of a panel of point mutations with only one hybridization
      per sample and could be automated to study many samples.

PMID- 11571714
TI  - Simultaneous allele-specific amplification: a strategy using modified primer
      template mismatches for SNP detection--application to prothrombin 20210A (factor
      II) and factor V Leiden (1691A) gene mutations.
AB  - BACKGROUND: Inherited thrombophilia is caused by mutations in genes central to
      the clotting cascade. Analysis of the factor V Leiden (FVL) and prothrombin
      G20210A mutations are the most prevalent in thrombophilia. METHODS AND RESULTS:
      We have optimized an allele-specific PCR assay for the simultaneous detection of
      both wild-type and mutant alleles. This method is adapted for clinical use with
      the FVL and prothrombin G20210A assays and is significant in its intentional use
      of nucleotide mismatches at the 3' end of allele-specific primers. Two internal
      allele-specific primers are designed to amplify in opposite directions on
      opposite strands that reduce differential amplification. Our results show
      concordance with methods involving PCR with restriction endonuclease digestion,
      yet are simpler to perform. CONCLUSION: The simultaneous allele-specific
      amplification method allows simultaneous detection of wild-type and mutant
      alleles by PCR using four distinct primers. Nucleotide mismatches in the primers
      reduce competitive amplification.

PMID- 11571715
TI  - Pharmacologic inhibition of the Bcr-Abl kinase with STI571: a novel, safe, and
      effective therapy for chronic myeloid leukemia.

PMID- 11571716
TI  - Therapeutic options for acute myelogenous leukemia.
AB  - BACKGROUND: General therapeutic options for patients with acute myelogenous
      leukemia (AML) are reviewed and specific new therapies are described. METHODS:
      Data in this review came from the published literature and the M. D. Anderson
      Cancer Center's acute leukemia database. RESULTS: Outcome following standard
      therapy of AML is so variable that is best to speak of a range of outcomes
      determined by various prognostic factors. Therapy can (and usually does) fail
      because of treatment-induced mortality or (more usually) resistance to therapy.
      Performance status and age are the principal predictors of early death, whereas
      cytogenetics, a history of abnormal blood counts, and MDR1 expression are
      predictors of resistance. Using this information, physicians can categorize
      patients into those in whom 1) standard therapy is indicated, 2) either standard
      or investigational therapy is appropriate, and 3) investigational therapy is
      indicated. The majority of even newly diagnosed patients belong to Group 3. The
      availability of allogeneic or autologous transplantation does not alter this
      conclusion. Investigational therapies have been developed that are directed
      against the CD33 surface antigen, the multidrug-resistant MDR1 protein, and other
      targets. Because of the number of new therapies clinical research in AML should
      emphasize pilot trials rather than traditionally large Phase III studies.
      CONCLUSIONS: Most patients with newly diagnosed AML should be offered
      investigational regimens.

PMID- 11571717
TI  - Hematologic recovery after central lymphatic irradiation for patients with stage
      I-III follicular lymphoma.
AB  - BACKGROUND: The authors previously reported that central lymphatic irradiation
      (CLI) can induce molecular remission in patients with Stage I-III follicular
      lymphoma, as measured by polymerase chain reaction analysis for t(14;18)
      (q32;q21). Hematologic toxicity has been considered a major consequence of CLI.
      This study was undertaken to analyze the patterns of hematologic recovery after
      CLI. METHODS: Thirty-three patients with Stage I-III follicular lymphoma were
      treated with CLI between January 1993 and February 1998. CLI consisted of
      irradiation to mantle, upper two-thirds of abdomen, and pelvic fields. Each field
      was treated to 30.0-30.6 grays (Gy) at 1.5-1.8 Gy per fraction, with a boost to
      36.0-39.6 Gy at the same rate to the sites of macroscopic disease. A break of
      approximately 4 weeks was given after treatment of each field. Twenty-four
      patients who were followed for a minimum of 1 year from the end of CLI form the
      basis of this analysis. Fourteen patients were male. Three patients had Stage I
      disease, 6 patients had Stage II disease, and 15 patients had Stage III disease.
      The International Prognostic Index (IPI) for malignant lymphoma was 0 for 5
      patients, 1 for 13 patients, and 2 for 6 patients. The Eastern Cooperative
      Oncology Group performance status was 0 for 21 patients and 1 for 3 patients. The
      median values for their pretreatment characteristics were as follows: age, 60
      years (range, 34-73 years); height, 173 cm (range, 155-193 cm); weight, 79 kg
      (range, 57-107 kg); body surface area (BSA), 1.95 m(2) (range, 1.61-2.31 m(2));
      bone marrow cellularity, 27%(range, 2-75%), platelet count, 233,000/mm(3) (range,
      139,000-339,000/mm(3)), white blood cell (WBC) counts, 6400/mm(3) (range, 4200
      10,900/mm(3)); and hemoglobin, 14.5 mg/dL (range, 11.8 -16.6 mg/dL). The median
      duration of CLI was 159 days (range, 137-345 days). Ten patients had
      cardiovascular disease. The number of sites receiving a boost dose of > or = 36.0
      Gy was 0 sites in 1 patient, 1 site in 6 patients, 2 sites in 11 patients, 3
      sites in 5 patients, and 4 sites in 1 patient. The platelet, hemoglobin, and WBC
      counts were followed every 3 months after completion of CLI. These counts were
      normalized to the pretreatment counts for statistical analyses. Univariate and
      multivariate analyses were performed to investigate the correlations between
      patient factors and hematologic status at 1 year posttreatment. Pearson
      correlation analysis was used for the continuous factors (patient age, height,
      weight, BSA, bone marrow cellularity, and duration of CLI), and the Mann-Whitney
      test was used for categoric factors (IPI, gender, performance status, stage,
      number of sites receiving > or = 36.0 Gy, and presence or absence of
      cardiovascular disease). RESULTS: There was continued recovery, essentially
      approaching the pretreatment levels, over 3 years for platelet, WBC, and
      hemoglobin counts. Factors that were associated significantly with normalized
      platelet counts at 1 year by univariate analyses were age (P = 0.015) and
      cardiovascular disease (P = 0.041). Age was the only significant factor by
      multivariate analyses, with older patients having lower platelet counts at 1 year
      posttreatment. No factors were found that were associated significantly with 1
      year normalized WBC or hemoglobin levels by either univariate or multivariate
      analyses. CONCLUSIONS: All three of the hematologic components (platelets, WBC,
      and hemoglobin) essentially recover after patients undergo CLI over a 3-year
      period. Older age was the only significant adverse factor that affected the
      platelet recovery, as detected by multivariate analysis. (c) 2001 American Cancer
      Society.

PMID- 11571718
TI  - Is sentinel lymph node biopsy reliable and indicated after preoperative
      chemotherapy in patients with breast carcinoma?
AB  - BACKGROUND: Many studies support the concept and accuracy of sentinel lymph node
      biopsy (SNB) for staging patients with breast carcinoma, which can be performed
      with low morbidity in lymph node negative patients. Preoperative chemotherapy
      (PC) plays an important role in the treatment of patients with operable breast
      carcinoma and is another approach with which to reduce radical surgery in
      patients with more advanced disease. It is of interest whether the sentinel lymph
      node accurately represents the axillary status after PC and, thus, whether the
      sentinel node concept can be applied to both groups. METHODS: Thirty-three
      patients underwent SNB after chemotherapy and prior to axillary lymph node
      dissection. RESULTS: The average greatest tumor dimension before chemotherapy (33
      mm +/- 2 mm) was significantly larger (P = 0.000) than after therapy (20 mm +/- 3
      mm). Histopathologic complete remission was seen in only three patients. One or
      two sentinel lymph nodes (average, 1.7 lymph nodes) were identified with
      certainty in 29 of 33 procedures and accurately predicted axillary lymph node
      status in all of these patients. Breast-conserving surgery was possible in 21
      patients (64%), and axillary lymph nodes were involved in 22 patients (67%).
      CONCLUSIONS: Even after patients undergo PC, SNB seems to be a reliable method
      for accurate staging of the axilla in those more advanced breast carcinoma. Thus,
      axillary dissection may be avoided in certain patients. Lymph node involvement
      seems to be likely in women with suspicious axillary findings before chemotherapy
      who have no visible sentinel lymph nodes on preoperative lymphosintigraphy and in
      patients without recurrent tumors. Further investigation of the SNB concept in
      this patient group should be evaluated in larger studies.

PMID- 11571719
TI  - Significant correlation of monocyte chemoattractant protein-1 expression with
      neovascularization and progression of breast carcinoma.
AB  - BACKGROUND: Macrophages often infiltrate into solid tumor tissues. Tumor
      associated macrophages (TAMs) are known to play a crucial role in tumor
      progression. Monocyte chemoattractant protein-1 (MCP-1) is one of the major
      chemokines capable of inducing chemotactic migration of monocytes. METHODS: With
      the objective of investigating the clinical significance of MCP-1, the authors
      analyzed the expression of MCP-1 and of some other molecules by
      immunohistochemistry in 230 samples of primary breast carcinoma tissue. MCP-1
      staining was performed using an anti-MCP-1 monoclonal antibody, and it was
      assessed by grading the percentage of stained cells. RESULTS: It was found that
      117 breast tumor specimens (51%) had intensive staining in tumor cells. The
      expression of MCP-1 in tumor cells had a significant correlation with the
      expression of thymidine phosphorylase and membrane type 1-matrix
      metalloproteinase. In addition, MCP-1 expression tended to be associated with the
      accumulation of TAMs, which were counted by CD68 staining, and with microvessel
      density. MCP-1 expression in TAMs was correlated significantly with the
      histologic vessel invasion of tumor cells. CONCLUSIONS: The results of this study
      suggest that MCP-1 may play key roles in macrophage recruitment, in the
      expression of angiogenic factors, and in the activation of matrix
      metalloproteinases in patients with breast carcinoma.

PMID- 11571720
TI  - Breast conservation therapy as a treatment option for the elderly. The M. D.
      Anderson experience.
AB  - BACKGROUND: Although almost half of all incidents of breast carcinoma occur in
      women age > or = 65 years, not enough is known about appropriate care for
      patients in this age group. The objective of the current study was to evaluate
      the role of breast conservation therapy in the management of breast carcinoma in
      women age > or = 65 years. METHODS: From 1970 to 1994, 1325 patients with
      carcinoma of the breast were treated with breast conservation therapy (segmental
      mastectomy and radiation therapy with or without axillary lymph node dissection)
      at The University of Texas M. D. Anderson Cancer Center. From this patient group,
      the authors identified 184 elderly women (> or = 65 years) with Stage 0-III
      disease at the time of diagnosis. RESULTS: The median patient age was 70 years
      (range, 65-88 years). The distribution of disease by stage among the women was
      Stage 0 disease in 12 patients (7%), Stage I disease in 107 patients (58%), Stage
      II disease in 63 patients (34%), and Stage III disease in 2 patients (1%).
      Comorbid conditions that may have influenced treatment planning were reported in
      91 patients (50%). An axillary lymph node dissection was performed in 135
      patients (73%), with positive axillary lymph nodes found in 30 patients (22%).
      Adjuvant chemotherapy was given to 10 patients (5%), and tamoxifen therapy was
      given to 63 patients (34%). Complications from treatment were reported in 24
      patients (13%). With a median follow-up of 7.3 years (range, 0.25-23.5 years), 9
      patients developed locoregional disease recurrence (5%), 10 patients developed
      contralateral breast carcinoma (5%), and 21 patients developed distant metastasis
      (11%). At last follow-up, 113 patients (61%) were alive, 15 patients (8%) were
      dead of disease, and 56 patients (30%) were dead of other causes. The 5-year and
      10-year disease specific survival rates were 96% and 91%, respectively.
      CONCLUSIONS: Breast conservation therapy with segmental mastectomy and
      postoperative radiation therapy with or without axillary lymph node dissection
      provides excellent local control and disease free survival in elderly women with
      breast carcinoma. This treatment should be considered as the standard of care for
      elderly patients without severe comorbid disease.

PMID- 11571721
TI  - Treatment with cisplatin and etoposide in patients with neuroendocrine tumors.
AB  - BACKGROUND: Patients with malignant endocrine pancreatic tumors (EPTs) are
      responsive to combinations of chemotherapy with streptozotocin and 5
      fluorouracil/doxorubicin, whereas patients with malignant carcinoids are not. For
      both categories of patients, alpha-interferon and/or somatostatin analogs can
      produce long-lasting responses. Cisplatin in combination with etoposide has been
      suggested to be effective in patients with malignant neuroendocrine carcinomas.
      The authors used this therapy as second-line or third-line treatment in patients
      with poorly differentiated and/or rapidly progressing disease. METHODS: Thirty
      six patients with histopathologically verified malignant neuroendocrine tumors
      were included: Eighteen tumors were of foregut origin, of which 5 were atypical,
      and 15 tumors were EPTs, of which 4 were poorly differentiated endocrine
      carcinomas. Three tumors were of midgut origin. The median patient age was 47.5
      years. The median duration of disease from the time of diagnosis was 12 months.
      All patients had metastatic disease. Thirty of 36 patients had received previous
      treatment. Etoposide was given at a dose of 100 mg/m(2) per day for 3 days, and
      cisplatin was given at a dose of 45 mg/m(2) on Days 2 and 3 as a continuous
      intravenous infusion that was repeated every 4 weeks. RESULTS: Ten of 18 patients
      with foregut carcinoids (56%) responded radiologically and/or biochemically, with
      a median duration of 9 months; and 7 of 14 patients with EPTs (50%) responded
      radiologically and/or biochemically, with a median duration of 9 months. No
      difference in response was seen between patients with atypical or typical foregut
      carcinoids or between patients with well differentiated or poorly differentiated
      endocrine pancreatic carcinoma. Nineteen of 36 patients (53%) experienced World
      Health Organization (WHO) Grade 1-2 nephrotoxicity, and 23 patients (64%)
      suffered from WHO Grade 3-4 neutropenia. CONCLUSIONS: The combination of
      cisplatin and etoposide can produce significant responses in patients with
      heavily pretreated and poorly differentiated/rapidly progressing neuroendocrine
      tumors. The toxicity is considerable, and nephrotoxicity is the dose limiting
      factor.

PMID- 11571722
TI  - Adjuvant chemotherapy for large cell carcinoma with neuroendocrine features.
AB  - BACKGROUND: In 1999, the World Health Organization categorized large cell
      neuroendocrine carcinoma, large cell carcinoma with neuroendocrine
      differentiation, and large cell carcinoma with neuroendocrine morphology as a
      variant of large cell carcinoma. Patients with large cell carcinoma with
      neuroendocrine features have poor prognoses, comparable to those for small cell
      lung carcinoma. Small cell lung carcinoma is sensitive to chemotherapy; however,
      it is still unclear whether large cell carcinoma with neuroendocrine features is
      responsive to adjuvant chemotherapy. METHODS: The authors analyzed 73 patients
      with large cell carcinoma with neuroendocrine features who underwent resection of
      the tumor and studied the effect of adjuvant chemotherapy for large cell
      carcinoma with neuroendocrine features. RESULTS: In patients with Stage I
      disease, the overall survival for patients with adjuvant chemotherapy based on
      cisplatin, carboplatin, or cyclophosphamide, which were used as standard
      chemotherapy for small cell lung carcinoma, were significantly higher than the
      overall survival for patients without adjuvant chemotherapy. In patients with
      Stage II, III, and IV disease, there was no significant difference between
      patients with adjuvant chemotherapy and without adjuvant chemotherapy.
      CONCLUSIONS: Adjuvant chemotherapy based on cisplatin, carboplatin, or
      cyclophosphamide prolongs survival of patients with large cell carcinoma with
      neuroendocrine features in early stage.

PMID- 11571723
TI  - Adrenocortical carcinoma. Clinical outcome at the end of the 20th century.
AB  - BACKGROUND: Adrenocortical carcinoma remains a rare and lethal neoplasm.
      Effective therapies have not emerged in recent decades. However, medical advances
      have improved diagnostic techniques and supportive measures; these changes may
      have a beneficial impact on the natural history of the disease. METHODS: The
      authors retrospectively analyzed the clinical outcomes of patients with
      adrenocortical carcinoma registered at the University of Texas M.D. Anderson
      Cancer Center focusing on patients who received their diagnosis since 1980 and
      comparing data from those patients with earlier reports. RESULTS: Since 1980, 139
      patients have registered at M.D. Anderson Cancer Center with the diagnosis of
      adrenocortical carcinoma. One-third had evidence of hormone hypersecretion, and
      one-third had localized disease at diagnosis. Men were affected as frequently as
      women but tended to be older and have larger tumors at diagnosis. The 5-year
      survival rate was 60% (Kaplan-Meier analysis). The 30 patients with the longest
      survival (> 5 years) and the 30 patients with the shortest survival (< 11 months)
      had no significant differences in age, gender, tumor size, or functionality.
      However, long-term survivors had significantly less extensive disease. A
      comparison with patients reviewed in earlier reports from the same institution
      showed no significant differences in gender predilection, tumor function, or
      extent of disease. Despite these similarities, patients whose disease was
      diagnosed since 1980 lived much longer than patients observed in earlier decades.
      CONCLUSIONS: Despite the lack of significant improvements in early diagnosis and
      effective therapies, patients with adrenocortical carcinoma are living longer (5
      year survival rate, 60%). It is important to revise assumptions regarding the
      clinical outcomes of patients with this disease.

PMID- 11571724
TI  - BCL2 expression correlates with metastatic potential in pancreatic cancer cell
      lines.
AB  - BACKGROUND: Programmed cell death (termed apoptosis) regulates normal tissue
      homeostasis. Loss of local paracrine signals and intercellular adhesion molecules
      are potent inducers of apoptosis and thereby eliminate normal cells that may have
      escaped beyond the confines of the local organ environment. Dysregulation in the
      expression of the BCL2 gene family, the prototypic regulators of apoptosis, is a
      common occurrence in cancer and imparts resistance to standard triggers of
      apoptosis. Therefore, the authors sought to examine whether abnormal BCL2 gene
      family expression correlated with resistance to apoptosis and increased
      metastatic potential in pancreatic carcinoma. METHODS: The authors examined BCL2
      expression and apoptotic sensitivity in three panels of human pancreatic cancer
      cell lines that possess varying metastatic potential. Stable transfectants were
      generated that overexpress BCL2. These transfectants were then analyzed for
      differences in metastasis formation in athymic mice. RESULTS: Among the isogenic
      panels of pancreatic cancer cell lines, BCL2 expression levels correlated with
      metastatic potential. Highly metastatic variants of each family of cell lines
      were more resistant to induction of apoptosis. Finally, using the BCL2
      transfectant in a xenograft model, elevated BCL2 expression led to a higher
      incidence of metastases. CONCLUSIONS: The authors conclude that increased BCL2
      expression correlates with apoptotic resistance and metastatic potential;
      dysregulation of BCL2 expression may be involved in the metastatic progression of
      pancreatic carcinoma.

PMID- 11571725
TI  - Prostate carcinoma risk and allelic variants of genes involved in androgen
      biosynthesis and metabolism pathways.
AB  - BACKGROUND: Ethnicity, when it is used to mean shared genetic inheritance within
      a group, has become one of the most important factors in determining prostate
      carcinoma risk. Genetic polymorphisms were hypothesized to be the probable
      explanation for differences in risk among ethnic groups. The authors evaluated
      the association between polymorphisms in genes involved in the androgen
      biosynthesis and metabolism pathway and the risk of prostate carcinoma. METHODS:
      Two hundred twenty-six patients with the pathologic diagnosis of sporadic
      prostate tumor and 156 healthy matched (age, ethnic group) male controls from a
      large epidemiologic cohort were genotyped for previously described polymorphisms
      in the androgen receptor (AR), 5alpha-reductase type II (SRD5A2), p450c17
      (CYP17), and aromatase (CYP19) genes. The different polymorphisms in prostate
      carcinoma patients also were analyzed according to age of onset, preoperative
      prostate-specific antigen level, tumor stage, and tumor grade. RESULTS: The
      distribution of the tetranucleotide simple tandem repeat polymorphism (STRP) in
      intron 4 of CYP19 was significantly different in control and cancer patients (P =
      0.012). The 171 allele and the 187 allele were associated with prostate carcinoma
      risk (P = 0.05 and P = 0.045, respectively). Conversely, no association was
      observed between prostate carcinoma risk and the other polymorphisms studied as
      follow: the CAG repeat in exon 1 of AR, the (TA)n dinucleotide repeat
      polymorphism in the 3' untranslated region, and the A49T or V89L substitutions in
      SDR5A2, the single base pair (bp) (a T to C transition) polymorphism that creates
      an additional Sp1-type (CCACC box) promoter site in CYP17. In prostate carcinoma
      patients, CAG repeats of AR, and TA repeats of SDR5A2 are associated with age of
      onset (P = 0.05 and P < 0.001, respectively). CONCLUSIONS: The association
      between the 171-bp allele of CYP19 and prostate carcinoma risk suggests that
      aromatase could be used as a new indicator for prostate carcinoma prevention in
      men of White French ethnogeographic origin. Conversely, it is possible that an
      individual carries both a high- and a low-risk marker (e.g., CYP17 A2 allele and
      V89L in SRD5A2) resulting in no overall difference in risk observed across the
      population. For these reasons, the development of a polygenic model,
      incorporating multiple loci from the individual genes may maximize the chance of
      identifying individuals with high-risk genotypes.

PMID- 11571726
TI  - Differential expression of angiopoietin-1 and angiopoietin-2 in colon carcinoma.
      A possible mechanism for the initiation of angiogenesis.
AB  - BACKGROUND: Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) are important
      regulators of endothelial cell (EC) survival. Current models suggest that an
      increase in Ang-2 expression in ECs leads to the initiation of angiogenesis. The
      authors hypothesized that the imbalance of Ang-1 and Ang-2 activities in colon
      carcinoma leads to a net gain in Ang-2 function. METHODS: Reverse transcriptase
      polymerase chain reaction (RT-PCR) analyses and immunofluorescent double-staining
      were performed to examine human colon carcinoma cell lines, surgical specimens,
      normal mucosa, and liver metastases for the expression of Ang-1 and Ang-2.
      RESULTS: RT-PCR analyses revealed that 7 of 18 colon carcinoma cell lines
      expressed Ang-1, and 14 of 18 colon carcinoma cell lines expressed Ang-2 (P <
      0.05). Of the surgical specimens from patients with colon carcinoma, 6 of 11
      specimens expressed Ang-1, and 11 of 11 specimens expressed Ang-2 (P < 0.05).
      However, Ang-1 and Ang-2 were expressed with relative equal frequency in normal
      mucosa (P = 0.62). Immunofluorescent staining (n = 20 specimens) revealed the
      presence of Ang-2 protein in normal mucosa and tumor epithelium, but Ang-1 was
      expressed only in normal mucosa. A similar pattern was found for hepatic
      colorectal metastases. Double staining for Ang-1 or Ang-2 and cytokeratin-22 (an
      epithelial marker) demonstrated that Ang-1 was produced by uninvolved, normal
      colonic epithelium, whereas Ang-2 was produced by normal and malignant colonic
      epithelium. CONCLUSIONS: In patients with colon carcinoma, Ang-2 is expressed
      ubiquitously in tumor epithelium, whereas expression of Ang-1 in tumor epithelium
      is rare. The net gain of Ang-2 activity is possibly an initiating factor for
      tumor angiogenesis.

PMID- 11571727
TI  - GLUT-1 expression in ovarian carcinoma: association with survival and response to
      chemotherapy.
AB  - BACKGROUND: Cancer cell growth is an energy-related process supported by an
      increased glucose metabolism. The objective of this study was to investigate the
      association of GLUT-1 with response to chemotherapy and outcome in patients with
      ovarian carcinoma. METHODS: Histologic sections of formalin fixed, paraffin
      embedded specimens from 113 primary ovarian carcinomas were stained for GLUT-1 by
      using polyclonal GLUT-1 antibody (Dako Co., Carpinteria, CA) and the labeled
      streptavidin biotin procedure. Intensity of GLUT-1 staining was compared with
      disease free survival (DFS), chemotherapy response, and other clinicopathologic
      characteristics. RESULTS: GLUT-1 cytoplasmic membrane staining was observed in 89
      of 104 (85.6%) malignant tumors. Poorly differentiated tumors showed a trend to
      overexpress the GLUT-1 protein compared with the more differentiated counterparts
      (27.6% vs. 8.7%; P = 0.08). Patients who experienced a complete clinical response
      to chemotherapy were more frequently GLUT-1 positive than GLUT-1 negative (80%
      vs. 51.5%; P = 0.036). In multivariate analysis of advanced stage disease,
      residual tumor (P = 0.0001) and high GLUT-1 expression levels (P = 0.028) were
      the only independent variables that maintained a significant association with
      response to chemotherapy (P = 0.0001; chi-square = 38.13). In the subgroup of
      Stage III-IV (International Federation of Gynecology and Obstetrics patients
      showing a complete clinical response, GLUT-1 overexpression was associated with a
      shorter DFS. The median time to progression was 30 months in GLUT-1 strongly
      positive cases (> 50% of cancer cells positive) versus 60 months in GLUT-1 weakly
      positive cases (< or = 50% of cancer cells positive; P = 0.024). CONCLUSIONS:
      GLUT-1 status is an independent prognostic factor of response to chemotherapy in
      advanced stage ovarian carcinoma. Moreover, patients overexpressing GLUT-1 show a
      significantly shorter DFS. These results suggest that the assessment of GLUT-1
      status may provide clinically useful prognostic information in patients with
      ovarian carcinoma.

PMID- 11571728
TI  - Risk factors of endometrial polyps resected from postmenopausal patients with
      breast carcinoma treated with tamoxifen.
AB  - BACKGROUND: Endometrial polyps are the most common endometrial pathology
      described in association with postmenopausal tamoxifen exposure. Up to 3% of
      these polyps may show malignant changes. However, to the authors' knowledge no
      one has described any risk factor for the development of this pathology in
      postmenopausal patients with breast carcinoma treated with tamoxifen. OBJECTIVE.
      The objective of this study was to evaluate whether risk factors can be
      identified for the development of endometrial polyps in postmenopausal patients
      with breast carcinoma treated with tamoxifen. METHODS: The authors reviewed the
      medical records of 54 postmenopausal patients with breast carcinoma in whom
      endometrial polyps were resected by hysteroscopy after at least 6 months of
      tamoxifen treatment (Group I). Demographic characteristics, health habits, risk
      factors for endometrial carcinoma, and clinical factors related to the primary
      breast disease were examined. The results were compared with those obtained from
      210 similar patients in whom hysteroscopy did not reveal any endometrial
      pathology (Group II). RESULTS: Age at menopause was significantly older, duration
      of breast disease was significantly longer, and body weight was significantly
      heavier among Group I patients compared with Group II patients (P = 0.0162, P =
      0.0026, and P = 0.0364, respectively). Endometrial thickness, measured by
      transvaginal ultrasonography, was significantly thicker in Group I patients (16.3
      +/- 7.2 mm) compared with that detected in Group II patients (11.8 +/- 6.3; P =
      0.0001). CONCLUSIONS: Various factors, such as older age at menopause, longer
      duration of breast disease, heavier weight, and thicker endometrium may
      contribute to the prediction of increased risk of development of endometrial
      polyps in postmenopausal patients with breast carcinoma treated with tamoxifen.

PMID- 11571729
TI  - A Phase I-II study of 96-hour infusional topotecan and paclitaxel for patients
      with recurrent Mullerian tumors.
AB  - BACKGROUND: Topotecan and paclitaxel are schedule dependent chemotherapeutic
      agents with activity against ovarian carcinoma. A Phase I-II study in which both
      drugs were administered concurrently by 96-hour, continuous, intravenous infusion
      was performed to determine the maximum tolerated dose (MTD), toxicities,
      pharmacokinetics, and efficacy of the combination. METHODS: Women with ovarian or
      primary peritoneal carcinoma and documented recurrent disease were eligible for
      the study. The dose of topotecan was escalated from 1.6 mg/m(2) while maintaining
      the paclitaxel dose constant at 100 mg/m(2). Plasma concentrations of both drugs
      were monitored daily during the first cycle of therapy. RESULTS: Forty-five
      patients with a median age of 54 years (range, 42-70 years) received 181 cycles
      of therapy. Five patients were recruited to each of four dose levels (topotecan
      1.6 mg/m(2), 2.0 mg/m(2), 2.8 mg/m(2), and 3.6 mg/m(2)), and an additional 25
      patients were treated at the MTD (Phase II). Neutropenia and thrombocytopenia
      became dose limiting toxicities (DLT) at the fourth dose level. Emesis,
      mucositis, peripheral neuropathy, diarrhea, and alopecia were mild. Twenty
      patients (44%) had line-related occlusion, thrombosis, or infection. The mean
      values (+/- standard deviation) of the apparent steady-state plasma
      concentrations at the Phase II doses were 2.3 nM +/- 0.5 nM for topotecan
      lactone, 5.6 nM +/- 2.1 nM for total topotecan, and 40.1 nM +/- 16.8 nM for
      paclitaxel. There were seven partial responses (Phase II) contributing to an
      objective response rate of 28% and a median survival time of 11.7 months (range,
      0.6-20.1 months). CONCLUSIONS: Topotecan at a dose of 2.8 mg/m(2) and paclitaxel
      at a dose of 100 mg/m(2) administered by concurrent, 96-hour, continuous
      intravenous infusions shows activity against tumors of Mullerian origin.

PMID- 11571730
TI  - Inhibition of the UCI-107 human ovarian carcinoma cell line by a targeted
      cytotoxic analog of somatostatin, AN-238.
AB  - BACKGROUND: Cytotoxic analogs of somatostatin (SST), such as AN-238, which
      consists of 2-pyrrolinodoxorubicin (AN-201) linked to the SST carrier RC-121, can
      be targeted to tumors that express SST receptors. Because SST receptors are
      present in ovarian carcinoma cells, the authors evaluated the effect of AN-238 on
      the UCI-107 ovarian carcinoma cell line. METHODS: An analysis of microsatellite
      alleles in cocultured SST receptor positive and receptor negative cells was used
      for the demonstration of in vitro targeting. The toxicity and antitumor effects
      of AN-238 in nude mice bearing UCI-107 human ovarian tumors were investigated
      with or without pharmacologic inhibition of serum carboxylesterases (CE). The
      expression of SST receptor subtypes was determined by reverse transcriptase
      polymerase chain reaction analysis, and the binding affinity of AN-238 to SST
      receptors was determined by radioligand assays. RESULTS: The proliferation of SST
      receptor positive UCI-107 cells in vitro was inhibited preferentially by AN-238.
      AN-238 showed high-affinity binding to UCI-107 tumor membranes at a 50%
      inhibition concentration of 3.39 nM +/- 0.74 nM. In vivo, the volume and weights
      of UCI-107 tumors treated with AN-238 were decreased by more than 60% (P < 0.05)
      compared with controls. Cytotoxic radical AN-201 or the unconjugated mixture of
      AN-201 with carrier RC-121 had no significant effects on tumors and were toxic.
      In mice with inhibited serum CE activity, AN-201 at 400 nmol/kg was lethal,
      whereas AN-238 at a total dose of 800 nmol/kg caused only 22% mortality and
      reduced tumor weight by 69% and volume by 70% (P < 0.05 vs. control).
      CONCLUSIONS: Targeted chemotherapy with the SST conjugate AN-238 inhibits SST
      receptor positive experimental ovarian tumors. AN-238 may provide a new treatment
      modality for patients with advanced ovarian carcinoma.

PMID- 11571731
TI  - Possible associations among expression of p14(ARF), p16(INK4a), p21(WAF1/CIP1),
      p27(KIP1), and p53 accumulation and the balance of apoptosis and cell
      proliferation in ovarian carcinomas.
AB  - BACKGROUND: Although there are several reports of changes in expression of cyclin
      dependent kinase inhibitors in ovarian carcinomas, little is known about their
      associations with tissue kinetics in the various histologic subtypes. METHODS: In
      total, 131 carcinomas were immunohistochemically investigated for expression of
      p14(ARF) (p14), p16(INK4a) (p16), p21(WAF1/Cip1) (p21), and p27(Kip1) (p27). The
      results also were compared with data for apoptosis, cell proliferation, p53
      status, and survival. Western blot and mRNA analyses were conducted on 35
      malignant ovarian tumor samples. RESULTS: Significant differences in tissue
      kinetics determined by ratios of apoptotic relative to mitotic indices were
      observed among histologic subtypes of ovarian carcinomas, showing a shift toward
      predominance of cell proliferation in serous and cell deletion in clear cell
      types. The expression of p16, p21, p27, and p53 was associated closely with
      changes in cell proliferation rather than apoptosis and survival, dependent on
      the subtype. Positivity for p16 and p21 in the Western blot assay was
      significantly related to the results for immunohistochemical but not mRNA
      analyses, indicating possible posttranscriptional regulation of these genes.
      CONCLUSIONS: The findings indicate that the several cyclin-dependent kinase
      inhibitors investigated are expressed differently among histologic subtypes of
      ovarian carcinomas, associated with differences in tissue kinetics and the
      balance of apoptosis and cell proliferation.

PMID- 11571732
TI  - The polymorphic CAG repeat in the androgen receptor gene in Jewish Israeli women
      with endometrial carcinoma.
AB  - BACKGROUND: Endometrial carcinoma is considered a hormonal-dependent tumor;
      estrogen induces endometrial cellular proliferation, whereas progestins display
      an antiproliferative effect on endometrial tissue. The role that androgen and its
      receptor (androgen receptor [AR]) play in the pathogenesis of endometrial
      carcinoma is less clear. Although androgen has an in vitro inhibitory effect on
      endometrial cell proliferation, up to 75% of endometrial carcinoma express AR
      somatically. A polymorphic CAG repeat within exon 1 of the AR encodes for a
      polyglutamine tract, with length range of 8 to 33 repeats, which is inversely
      correlated with the transcriptional activity of the AR. METHODS: To gain insight
      into the role of AR in endometrial carcinoma, the authors analyzed the
      polymorphic CAG repeat in 79 Jewish Israeli patients with endometrial carcinoma
      as compared with 44 healthy Jewish women serving as controls. Analysis was
      conducted using germline DNA as template and using polymerase chain reaction
      primers flanking the CAG repeat with subsequent fluorescent determination of
      allele sizes. RESULTS: Allele size range of the longer of the two alleles in the
      patients was 11-33 (mean, 19.8 +/- 2.7) and in the controls 10-22 (mean, 17.9 +/-
      1.9), a statistically significant difference (P < 0.01). Allele size variation
      within the patient group did not correlate with disease stage, grade,
      reproductive history, or age at diagnosis. CONCLUSIONS: The authors conclude that
      AR-CAG repeat length differs in Jewish patients with endometrial carcinoma as
      compared with healthy individuals in Israel, and this finding increases the
      possibility that the AR is involved in the predisposition to this neoplasm.

PMID- 11571733
TI  - Upper respiratory tract carcinoma with chromosomal translocation 15;19: evidence
      for a distinct disease entity of young patients with a rapidly fatal course.
AB  - BACKGROUND: Carcinoma of the upper respiratory tract is rare in childhood, and
      cytogenetic aberrations have not been characterized in this population. The
      chromosomal translocation 15;19 has been reported four times previously. All
      patients were young and had tumors arising in the thorax. The three reports that
      provide clinical follow-up all describe superior vena cava syndrome and death
      soon after presentation. All tumors were diagnosed as carcinoma (three
      undifferentiated, one mucoepidermoid), and the authors suggested thymus, lung, or
      germ cell origin. METHODS: The authors investigated the clinical and pathologic
      findings in two patients with poorly differentiated carcinoma showing evidence of
      t(15;19). This included a 13-year-old girl with a rapidly growing epiglottic
      mass, leading to superior vena cava syndrome and death and a 12-year-old girl
      with an aggressive nasopharyngeal mass showing intracranial extension. RESULTS:
      The laryngeal tumor was poorly differentiated, with vesicular nuclei, prominent
      nucleoli, extensive necrosis, and a lymphoplasmacytic infiltrate; cells were
      positive for cytokeratin and negative for lymphoma, melanoma, germ cell, and
      endocrine markers. Electron microscopy showed rare intermediate junctions and
      basal lamina. The nasopharyngeal tumor was poorly differentiated with areas of
      obvious squamous differentiation observed histologically, immunophenotypically,
      and ultrastructurally. Cytogenetic and fluorescent in situ hybridization studies
      were consistent with t(15;19)(q13;p13.1) in both cases. Both children received
      chemo- and radiotherapy. The first child died of disease after 36 weeks; autopsy
      revealed tumor in the larynx with spread to the skin/subcutis (neck and thorax)
      and lymph nodes (cervical, subcarinal, and pulmonary hilar). The second child
      developed widespread bony metastases and died of disease after 13 weeks.
      CONCLUSIONS: In conjunction with previous reports, the authors' findings show
      that t(15;19) is part of a distinct clinicopathologic entity characterized by
      young age, midline carcinoma of the neck or upper thorax, and a rapidly fatal
      course. Female gender and superior vena cava syndrome are common. The
      histogenesis of these distinctive tumors is unknown. The authors' findings
      suggest origin in the upper airway, perhaps from submucosal glands.

PMID- 11571734
TI  - A randomized, prospective trial of central venous ports connected to standard
      open-ended or Groshong catheters in adult oncology patients.
AB  - BACKGROUND: Implanted central venous access is practiced extensively in oncology;
      however, information on the relevance of using the device with a valved catheter
      (Groshong), compared with an open-ended catheter, is scarce. The authors
      investigated the two types of catheters in a randomized trial using the same type
      of subcutaneous port and evaluated efficacy as well as early and late
      complications. METHODS: Three hundred four patients with malignant disease (solid
      tumors) who were eligible to receive intravenous chemotherapy were accrued during
      a 15-month period. After providing informed consent, the patients were assigned
      randomly to implantation of a titanium and silicone, rubber port (Dome Port; Bard
      Inc., Salt Lake City, UT) attached either to an 8.0-F silastic Groshongtrade mark
      catheter tube (experimental group) or to a 9.6-F silastic open-ended catheter
      tube (control group). Both catheters were manufactured by Bard Inc. Implantation,
      care, and follow-up followed the same protocol guidelines until removal of the
      device, death, or ending of the study. Power and color Doppler ultrasound
      examinations of internal jugular and subclavian veins were performed at 1 month
      and at 4 months or at anytime when a venous thrombosis was suspected. RESULTS:
      Three hundred two patients (99.3%) were evaluable, 150 patients in the control
      group and 152 in the experimental group. The median follow-up was 237 days. There
      was a trend toward more early complications in the experimental group (5.9%; 95%
      confidence interval [95% CI], 2.7-10.9%) than in the control group (2.7%; 95% CI,
      0.7-6.7%), although the difference was not statistically significant (P = 0.26).
      There was also a trend toward more late complications in the experimental group
      (17.1%; 95% CI, 11.5-24.1%) compared with the control group (10.7%; 95% CI, 6.2
      16.7%; P = 0.13), although the difference, again, was not statistically
      significant. The most frequent late complication was the inability to draw blood
      samples (12.5% in the experimental group and 2% in the control group; P < 0.001).
      Sepsis was observed in 1 patient and in 3 patients and venous thrombosis was
      observed in 6 patients and in 11 patients in the experimental and control
      treatment groups, respectively (P value not significant). CONCLUSIONS: In the
      tested clinical setting, the use of a Groshong catheter was not superior to a
      traditional, open-ended device in terms of early and late complications of the
      implant and its use. The theoretical justification for its superiority for more
      efficient use of the implantable device could not be substantiated.

PMID- 11571735
TI  - Dose-escalating conformal thoracic radiation therapy with induction and
      concurrent carboplatin/paclitaxel in unresectable stage IIIA/B nonsmall cell lung
      carcinoma: a modified phase I/II trial.
AB  - BACKGROUND: A modified Phase I/II trial was conducted evaluating the
      incorporation of three-dimensional conformal radiation therapy into a strategy of
      sequential and concurrent carboplatin/paclitaxel in Stage III unresectable
      nonsmall cell lung carcinoma (NSCLC). The dose of thoracic conformal radiation
      therapy (TCRT) from 60 to 74 gray (Gy) was increased. Endpoints included response
      rate, toxicity, and survival. METHODS: Sixty-two patients with unresectable Stage
      III NSCLC were included. Patients received 2 cycles of induction carboplatin
      (area under the concentration curve [AUC], 6) and paclitaxel (225 mg/m(2) over 3
      hours) every 21 days. On Day 43, concurrent TCRT and weekly (x 6) carboplatin
      (AUC, 2) and paclitaxel (45 mg/m(2)/3 hours) were initiated. The TCRT dose was
      escalated from 60 to 74 Gy in 4 cohorts (60, 66, 70, and 74 Gy). RESULTS: The
      response rate to induction carboplatin/paclitaxel was 40%. Eight patients (13%)
      progressed on the induction phase. No dose-limiting toxicity was observed during
      the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was
      esophagitis, however, only 8% developed Grade 3/4 esophagitis using Radiation
      Therapy Oncology Group criteria. The overall response rate was 52%. Survival
      rates at 1, 2, 3, and 4 years were 71%, 52%, 40%, and 36%, respectively, with a
      median survival of 26 months. The 1-, 2-, and 3-year progression free survival
      probabilities were 47%, 35%, and 29%, respectively. CONCLUSIONS: Incorporation of
      TCRT with sequential and concurrent carboplatin/paclitaxel is feasible, and dose
      escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall
      response and survival rates are encouraging. Both locoregional and distant
      failure remain problematic in this population of patients.

PMID- 11571736
TI  - Hyaluronan content in pleural fluid as a prognostic factor in patients with
      malignant pleural mesothelioma.
AB  - BACKGROUND: Regardless of the modality of therapy used, malignant pleural
      mesothelioma is a highly treatment-resistant and invariably fatal disease.
      Identification of prognostic variables are important for future investigational
      therapeutic studies. METHODS: The prognostic significance of various clinical
      variables, including hyaluronan levels in pleural fluid, was evaluated in a
      retrospective analysis in 100 patients with histologically confirmed malignant
      pleural mesothelioma. RESULTS: The overall median survival was 11.5 months.
      Univariate analyses identified histologic subtype, i.e., epithelial or mixed, and
      elevated content of hyaluronan in the pleural effusion as significant prognostic
      variables. A multivariate analysis confirmed the independent predictive power of
      histologic subtype, and an elevated concentration of hyaluronan in the pleural
      fluid also indicated longer survival in older patients and in patients receiving
      therapy other than supportive. CONCLUSIONS: The prognostic value of histologic
      subtype and the concentration of hyaluronan in pleural effusions should be
      considered when designing and evaluating treatment trials for patients with
      malignant pleural mesothelioma.

PMID- 11571737
TI  - Variant expression of CD44 in preneoplastic lesions of the lung.
AB  - BACKGROUND: Specific CD44 isoforms are cell surface adhesion molecules and have
      been shown to be associated with tumor progression and metastasis. In lung
      carcinoma, CD44 expression has been reported to be a feature of nonsmall cell
      lung carcinoma (NSCLC) but not small cell lung carcinoma. A specific variant,
      CD44v6, was shown to be expressed only in a subset of NSCLC, namely the squamous
      cell and bronchoalveolar carcinomas, suggesting that CD44 may play a role in lung
      carcinoma differentiation. METHODS: To determine whether differential CD44
      expression is an early event in the pathogenesis of lung carcinoma, the authors
      investigated the pattern of expression of the standard (CD44s) and variant
      (CD44v6) isoforms by immunohistochemistry in normal lung, nonneoplastic
      specimens, and bronchial biopsies of preneoplastic lesions. RESULTS: In normal
      bronchial epithelium and all nonneoplastic cases, CD44s expression was limited to
      the basement membrane and adjacent lower strata of the epithelium, whereas CD44v6
      was expressed within the basement membrane only. However, aberrant expression of
      both CD44s and CD44v6 was observed in all preneoplastic lesions examined. In
      cases of dysplasia, squamous metaplasia, goblet cell hyperplasia, and basal cell
      hyperplasia, all epithelial strata showed immunoreactivity for both isoforms, in
      contrast to normal epithelium, in which immunoreactivity was noted to be
      restricted to the basal layer cells. In contrast, CD44s and CD44v6 expression was
      completely absent in nearly all cases of adenomatosis. CONCLUSIONS: Altered CD44s
      and/or CD44v6 expression appears to be a feature of all preneoplastic lesions in
      the lung, the precise nature of which varies according to histologic tumor type.
      Therefore, the authors conclude that CD44s and CD44v6 may lend themselves to be
      markers of preneoplastic changes in the lung.

PMID- 11571738
TI  - Expression of apoptosis-related proteins, p53, and DNA fragmentation in sarcomas
      of the pulmonary artery.
AB  - BACKGROUND: Apoptosis is a common feature in a variety of pathologic conditions.
      Induction of apoptosis through apoptotic stimuli such as, chemotherapy or
      radiation, presents new insights into tumor biology and therapy. In particular,
      members of the Bcl-2 family as well as the Fas system are known to be involved in
      the regulation of apoptosis in different tumor entities. METHODS: In the current
      study, the expression of the apoptosis-related molecules p53, Bax, Bcl-2, Fas
      (CD95), Fas-Ligand and perforin was examined in 7 patients with a sarcoma of the
      pulmonary artery. Furthermore, the TUNEL-method for the detection of apoptotic
      cells was applied as well as sequencing of the p53 gene. RESULTS: In the TUNEL
      assay, approximately 10% of the sarcoma cells displayed DNA fragmentation. In
      addition, Bax was expressed in tumor cells. Accumulation of p53 was evident in 4
      of 7 patients (pAB 240 antibody), and 2 of them were positive for the pAB 1801
      antibody. Only 1 case had a point mutation in Exon 5 of the p53 sequence. A few
      tumor cells showed a double labeling of Bax and p53. Bcl-2 could be detected only
      in tumor-associated lymphocytes. Finally, several lymphocytes could be stained
      with perforin, but none of the specimens showed a reactivity for Fas or Fas
      Ligand. CONCLUSION: The expression of Bax indicated a possible role of this
      molecule in programmed cell death in pulmonary sarcomas. The limited coexpression
      of Bax and p53 suggested that induction of Bax can occur independently of p53.
      The detection of perforin in lymphocytes suggested a possible role for this
      molecule in apoptosis of the sarcoma cells. In contrast, the Fas system did not
      seem to play an essential role in sarcomas of the great vessels.

PMID- 11571739
TI  - p27(kip1) immunoreactivity correlates with long-term survival in pleural
      malignant mesothelioma.
AB  - BACKGROUND: Pleural malignant mesothelioma (PMM) is a rare and highly aggressive
      tumor, whose development is strictly related to occupational exposure to
      asbestos. The prognosis of PMM is generally poor (median survival, 4-12 months),
      but a few have a relatively long survival. The objective of this study was to
      evaluate the use of the cell cycle-related proteins p27(kip1) and MIB-1 as
      prognostic indicators of survival in PMMs. METHODS: Of 621 PMMs, the authors
      selected 27 cases with a relatively long-term survival (> 24 months) and a
      control group of 36 PMMs having a shorter (usual) survival (< 24 months).
      RESULTS: The expression of the p27(kip1) was significantly higher in the long
      term survival group compared with the control (short survival) group (81.41% vs.
      31.94%; P < 0.0001). The PMMs of epithelioid histotype had a significantly higher
      p27(kip1) immunoreactivity compared with those of biphasic type (59.24% vs.
      38.94%; P = 0.02). In agreement with the data in the literature, the
      proliferative activity (as detected by MIB-1 immunoreactivity) was significantly
      higher in short than long survival PMMs (43.53% vs. 14.11%; P < 0.0001) and in
      the biphasic histotype than in the epithelioid type (43.19% vs. 26.02%; P =
      0.006). CONCLUSIONS: The combined expression of high/low p27(kip1) and low/high
      Ki-67 values identified with 100% specificity and sensitivity long versus short
      survivors. p27(kip1) represents a reliable additional predictive factor for PMMs
      and a useful marker to identify patients having a more favorable prognosis.

PMID- 11571740
TI  - Detection of tumor cells in the portal and peripheral blood of patients with
      colorectal carcinoma using competitive reverse transcriptase-polymerase chain
      reaction.
AB  - BACKGROUND: In spite of many reports, it remains unclear whether the presence of
      tumor cells in circulating blood flow predicts a poor prognosis. METHODS:
      Competitive seminested reverse transcriptase-polymerase chain reaction (RT-PCR),
      a technique for the quantitative detection of tumor cells, was applied to detect
      the presence of tumor cells in portal and peripheral blood samples from 121
      patients with colorectal carcinoma and to clarify their clinical significance.
      This technique can detect one carcinoembryonic antigen (CEA) mRNA-expressing
      tumor cell in 1 x 10(5) normal lymphocytes. RESULTS: Six of 33 healthy volunteers
      (18%) demonstrated a positive reaction to this technique. CEA mRNA expression was
      detected in the portal blood in 51% of patients and in the peripheral blood in
      42% of patients. The results from the two blood samples were consistent in 91% of
      patients. The positive expression rates for portal blood in patients with T1
      tumors and those with TNM Stage I disease were 38% and 45%, respectively. The
      positive rate was significantly higher in patients with colon carcinoma and those
      with Stage III or IV disease. CEA mRNA expression, quantitatively measured (x 10(
      8)/beta-actin), was 22.9 +/- 35.1 in the portal blood and 19.9 +/- 40.0 in the
      peripheral blood, with no statistically significant difference. A significant
      positive correlation was noted between portal and peripheral CEA mRNA expression
      levels according to Spearman correlation analysis (correlation coefficient =
      0.78; P < 0.01). Multivariate analysis revealed that the positive rate and level
      of CEA mRNA expression in the portal and peripheral blood did not appear to be
      influenced by the established prognostic factors. CONCLUSIONS: The presence of
      circulating tumor cells might be of less value as a prognostic factor because
      they also can be detected in patients with early-stage colorectal carcinoma and
      appeared to be independent of the conventional prognostic factors.

PMID- 11571741
TI  - Low-dose chemotherapy with methotrexate and vinblastine for patients with
      advanced aggressive fibromatosis.
AB  - BACKGROUND: This Phase II study was undertaken to assess the activity of
      methotrexate plus vinblastine in the treatment of patients with inoperable
      aggressive fibromatosis (AF) and to observe the evolution of the disease after
      such low-dose chemotherapy. METHODS: Thirty patients with a median age of 27
      years who were affected by primary (20%) or recurrent (80%), advanced, inoperable
      AF were treated with weekly methotrexate at a dose of 30 mg/m(2) plus vinblastine
      at a dose of 6 mg/m(2) for a median interval of 1 year. Patients with recurrent
      disease had received surgery, radiotherapy, tamoxifen, and antracycline-based
      chemotherapy. Tumor response was assessed in all patients as well as time to
      disease progression. RESULTS: Eighteen patients (60%) showed stable disease or
      minor tumor shrinkage along with symptom relief. A partial response was detected
      in 12 patients (40%). No complete responses were observed, and no patients had
      tumor progression during treatment. Four patients received fewer than 15 cycles
      of chemotherapy, mainly because of severe myelotoxicity. One of these patients
      died of local disease progression 33 months later, and the other three patients
      were stable. After a median follow-up of 75 months, the 10-year actuarial
      progression free interval is 67%. CONCLUSIONS: Methotrexate plus vinblastine
      given every 7-10 days for several months is associated with prolonged stable
      disease in a substantial subset of patients with advanced (inoperable) aggressive
      fibromatosis.

PMID- 11571742
TI  - A Phase I trial of H-ras antisense oligonucleotide ISIS 2503 administered as a
      continuous intravenous infusion in patients with advanced carcinoma.
AB  - BACKGROUND: Abnormal expression of Ras proteins frequently is found with
      oncogenic transformation making ras a promising therapeutic target. ISIS 2503 is
      a 20-base antisense phosphorothioate oligodeoxyribonucleotide that specifically
      downregulates H-ras expression and inhibits tumor cell growth in preclinical
      studies. Here, the authors report an initial clinical study of the safety and
      tolerability of an intravenous infusion of ISIS 2503 in patients with advanced
      cancer. METHODS: A continuous intravenous infusion of ISIS 2503 was administered
      for 14 days every 3 weeks to 23 patients with a variety of solid tumors
      refractory to standard therapy. The dose of ISIS 2503 was increased in sequential
      cohorts of patients, as toxicity allowed, until a final dose of 10.0 mg/kg/day of
      body weight was reached. Toxicity was scored by the National Cancer Institute's
      Common Toxicity Criteria, and tumor response was monitored after every two
      treatment cycles. Pharmacokinetic studies were performed in some of the patients
      up to, and including, the final dose of 10 mg/kg/day/day of body weight. Levels
      of H-ras mRNA expression also were determined in the circulating lymphocytes of
      some patients by quantitative reverse transcriptase-polymerase chain reaction.
      RESULTS: A total of 23 patients received 63 cycles of ISIS 2503 at escalating
      doses to 10.0 mg/kg/day without dose-limiting toxicity and only minimal side
      effects. Four patients had stabilization of their disease for 6-10 cycles. No
      consistent decreases in H-ras mRNA levels were observed in peripheral blood
      lymphocytes. CONCLUSIONS: ISIS 2503, an antisense oligonucleotide against H-ras,
      was well tolerated as a single agent at doses up to 10.0 mg/kg/day by 14-day
      continuous intravenous infusion. Several patients had stabilization of disease,
      suggesting that ISIS 2503 had some tumor growth inhibitory effects and future
      trials of ISIS 2503 in combination with chemotherapy should be considered.

PMID- 11571743
TI  - The use of trimodality therapy for the treatment of operable esophageal carcinoma
      in the veteran population: patient survival and outcome analysis.
AB  - BACKGROUND: In an effort to improve the cure rates associated with surgical
      therapy, neoadjuvant chemoradiotherapy is being used with increasing frequency
      before resection (trimodality therapy). A variety of clinical trials have
      reviewed this approach, but only one study to the authors' knowledge has shown a
      survival benefit for trimodality therapy. The extent to which trimodality therapy
      has gained acceptance in general practice is not clear. The objective of the
      current study was to determine the extent to which both surgery and trimodality
      therapy are used for the management of esophageal carcinoma within a large,
      national health care system and to determine the outcome of patients treated with
      these treatment approaches. METHODS: The current study was a retrospective cohort
      study. The study population was comprised of all veterans who underwent either
      surgery alone or trimodality therapy for operable esophageal carcinoma between
      the fiscal years of 1993 and 1997. Data were obtained from the Veterans
      Administration Patient Treatment File, Outpatient Clinic File, and the
      Beneficiary Identification Record Locator System. The main outcome measures were
      perioperative mortality and patient survival. RESULTS: During the study period,
      695 patients underwent either surgery alone or trimodality therapy for esophageal
      carcinoma. Five hundred thirty-four (77%) patients were treated with surgery
      only. One hundred sixty-one (23%) patients underwent surgery after induction
      chemoradiotherapy (trimodality therapy). Patients selected for trimodality
      therapy were younger (mean age, 60.8 years vs. 65.6 years), had fewer
      comorbidities, and were more likely to have a midesophageal tumor. The median
      survival for all patients was 15.2 months. The type of treatment had no apparent
      effect on survival. Favorable prognostic factors included younger age, a distal
      esophageal tumor, and the absence of metastases. The overall perioperative
      mortality was 13.7 %. The use of trimodality therapy did not increase
      perioperative mortality. CONCLUSIONS: Trimodality therapy is commonly used within
      the VA system. The nonrandomized nature of this study does not allow comparison
      of trimodality therapy to surgery alone, but the overall survival was limited for
      all patients. The predictors of survival are related to the biology of the
      disease, and they include patient age, tumor location, and stage at diagnosis.

PMID- 11571744
TI  - Defining the optimal radiation dose with three-dimensional conformal radiation
      therapy for patients with nonmetastatic prostate carcinoma by using recursive
      partitioning techniques.
AB  - BACKGROUND: The objective of this study was to determine the effect of dose and
      its interaction with known prognostic variables, including pretreatment prostate
      specific antigen (PSA), Gleason score (GS), and T classification, on patients
      with nonmetastatic prostate carcinoma treated with three-dimensional conformal
      radiation therapy (3DCRT) alone using recursive partitioning analysis. METHODS:
      Between November 1987 and November 1997, 939 patients with nonmetastatic prostate
      carcinoma were treated with 3DCRT alone at Fox Chase Cancer Center. Biochemical
      no evidence of disease (bNED) control was defined using the American Society of
      Therapeutic Radiology and Oncology Consensus definition. Recursive partitioning
      analysis was used to identify subgroups with similar risks of bNED failure.
      Prognostic factors used in the model included pretreatment PSA, GS, T
      classification, and radiation dose. The median follow-up was 47 months (range, 2
      133 months). RESULTS: Twelve terminal nodes of the decision tree were merged to
      form four prognostic groups with similar bNED control rates. The 5-year actuarial
      rates of bNED control rates for Groups I, II, III, and IV were 84%, 41%, 16%, and
      67%, respectively (P < 0.0001). Increasing the dose to greater than 7235
      centigray (cGy) improved bNED control rates for patients with PSA levels of 10
      19.9 ng/mL and T1/2a classification disease. Increasing the dose to greater than
      7629 cGy improved bNED control rates for patients with T2b/3 classification
      disease with PSA levels less than 20 ng/mL. Patients with PSA levels greater than
      or equal to 20 ng/mL need high-dose 3DCRT. For those patients with GS 2-6 and
      T1/2a classification disease, treatment with greater than 7400 cGy resulted in
      67% bNED control rate versus 16% at 5 years for treatment with less than 7400
      cGy. High radiation dose (> 7700 cGy) improved bNED control rate from 16% to 41%
      for patients with high-risk disease (PSA > or = 20 ng/mL and GS 7-10) at 5 years.
      CONCLUSIONS: The authors showed that with recursive partitioning techniques
      radiation dose continues to be an important predictor of bNED control rate and
      that a radiation dose response for patients with clinically localized prostate
      carcinoma exists. Patients with one or more prognostic feature (PSA > 10 ng/mL,
      classification T2b/T3, GS 7-10, or the presence of perineural invasion) achieve
      similar rates of bNED control compared with those patients with lower volume
      disease when radiation dose is increased.

PMID- 11571745
TI  - Impact of surgery and chemotherapy on the quality of life of younger women with
      breast carcinoma: a prospective study.
AB  - BACKGROUND: Studies that prospectively and simultaneously evaluate, within the
      first year of diagnosis, the impact of surgery and chemotherapy on quality of
      life (QOL) of younger women (60 years or younger) with early stage breast
      carcinoma are limited. METHODS: Quality of life of 103 women who had surgery
      (lumpectomy, 49; mastectomy, 54) approximately 1 month before the start of the
      study was evaluated at baseline and again after 5 months. Thirty-two women
      received chemotherapy during the study. RESULTS: Over time, subjects reported
      improvement in body image and physical, emotional, and functional well-being (P <
      0.001). They were less bothered by swollen/tender arms and worried less about
      risk of cancer to family members (P < 0.001). However, satisfaction with sex
      life, social support, and social/family well-being declined (P < 0.001). In the
      period closer to surgery, women with mastectomy reported poorer body image (P =
      0.001) and worse functional (P = 0.08) and physical well-being (P = 0.10). Women
      with lumpectomy worried more about the effects of stress on their illness (P <
      0.01) and had lower emotional well-being (P = 0.06). By 6 months after surgery,
      the two groups reported similar QOL scores. Chemotherapy had a negative impact on
      women's sexual functioning (P = 0.01) and their physical well-being (P = 0.09).
      Women who received chemotherapy also reported more shortness of breath (P =
      0.07). Post hoc analysis showed that women with breast reconstruction had higher
      emotional well-being at baseline than those with lumpectomy (P = 0.001) and
      mastectomy alone (P < 0.01). CONCLUSIONS: Younger women with breast carcinoma
      could experience a range of adjustment problems at various points in the
      treatment cycle. Interventions that would help reduce the negative impact of
      treatment on QOL need to be designed and integrated into routine clinical
      practice.

PMID- 11571746
TI  - The influence of urbanization, age, ethnicity, and income on the early diagnosis
      of breast carcinoma: opportunity for screening improvement.
AB  - BACKGROUND: Because most risk factors for breast carcinoma are not readily
      amenable to primary prevention, and early diagnosis is a powerful prognostic
      determinant, screening for the disease is crucial. Consequently, assessment of
      the progress and comprehensiveness of screening and other breast carcinoma early
      detection activities is important. The relative frequency of early diagnosis may
      provide a useful indicator of such activities. Nationwide, time trends in the
      early diagnosis of breast carcinoma have been improving for decades, but not all
      population subgroups may have benefited equally. METHODS: Using 1994-1997 data
      from the California Cancer Registry (CCR), a review of diagnostic patterns of in
      situ and local stage breast carcinoma was undertaken. For analytic purposes, the
      CCR includes 10 regional registries and 36 county reporting groups. Three early
      diagnostic measures were designated, including in situ breast carcinoma with
      tumor size < 10 mm in greatest dimension, in situ breast carcinoma, and localized
      breast carcinoma with tumor size < 21 mm in greatest dimension. These are
      referred to hereinafter as early diagnosis breast carcinomas. RESULTS: The
      percentage of early diagnosis breast carcinomas differed markedly by age,
      ethnicity, diagnosis year, and county of residence. Lower percentages of early
      diagnosis breast carcinomas were diagnosed in older women age >/= 85 years.
      Hispanic women were diagnosed with lower levels of in situ breast carcinoma.
      Hispanic and black women were diagnosed with less localized breast tumors of
      small size. There was an increase in the percentage of early diagnosis breast
      carcinomas over the 4-year observation period. Lower percentages of early
      diagnosis breast carcinomas were reported for the nonurban county/county groups,
      which were characterized by greater distances, lower population density, and
      lower household incomes. CONCLUSIONS: The authors conclude that elderly women,
      Hispanic and black women, and women who reside in nonurban areas should be
      targeted as high-priority subpopulations for mammographic screening.

PMID- 11571747
TI  - Making effective use of tumor registries for cancer survivorship research.
AB  - BACKGROUND: The growing number of cancer survivors has created an increased need
      for survivorship research; however, the identification and recruitment of cancer
      survivors present some challenges. This report describes how two hospital cancer
      registries were used to recruit a large sample of breast cancer survivors (BCS)
      for a study examining the late reproductive effects of breast cancer treatments.
      Limitations and opportunities associated with this type of recruitment strategy
      are described, and the overall success of recruitment using this approach is
      presented. METHODS: Tumor registries from a comprehensive cancer center and a
      community hospital were used to identify BCS who met the study screening
      criteria. Invitations and response forms were mailed to all potentially eligible
      women, and those who did not respond by mail also were contacted by telephone.
      Women who indicated interest and met the study requirements were asked to give
      written consent, were enrolled in the study, and were sent a self-report
      questionnaire. RESULTS: Seventy percent of the eligible women (n = 733 women)
      responded to the mailing. Seventy-seven percent of the 512 respondents indicated
      a willingness to participate and were sent a questionnaire. Of these, 78% (n =
      368 women) completed questionnaires. BCS recruited from the cancer center
      registry were more likely than those from the community hospital registry to
      respond to the invitation form (P = 0.033) and were more likely to return a
      completed questionnaire (P = 0.001). However, the community hospital provided
      access to a more ethnically diverse sample of survivors. CONCLUSIONS: The two
      participating cancer registries were an excellent source for identifying a large
      sample of long-term BCS, and the different types of registries provided greater
      sample size and diversity. Although there are some limitations to this approach,
      including nonresponse of a significant number of BCS, tumor registries represent
      an important resource for the rapid identification of cancer survivors for
      research studies. Findings from this study suggest several enhancements for
      future studies that may increase the yield from registry recruitment.

PMID- 11571748
TI  - Lifestyle high-risk behaviors and demographics may predict the level of
      participation in sun-protection behaviors and skin cancer primary prevention in
      the United States: results of the 1998 National Health Interview Survey.
AB  - BACKGROUND: Sun and ultraviolet radiation exposure are major risk factors for
      skin cancer, and sun-protective behaviors and skin cancer examinations are means
      of primary prevention of skin cancer. The objective of this study was to evaluate
      the extent to which demographics and other high-risk behaviors may predict the
      reported level of participation in sun-protection behaviors and skin cancer
      primary prevention in the United States adult population. METHODS: Data on
      reported sun-protection behaviors and skin cancer examinations were obtained from
      surveys completed by adults in the 1998 National Health Interview Survey.
      Univariate and multivariate data analyses were performed using specialized
      statistics software. RESULTS: For the United States adult population surveyed (n
      = 32,440), only 21% of those surveyed indicated that they had ever had a skin
      cancer examination, and, of those, only 45% indicated that the skin cancer
      examination was within the past year. For sun-protective behaviors, only 23%,
      27%, and 30% of those surveyed reported that they were very likely to wear
      protective clothing, stay in the shade, and use sunscreen, respectively.
      CONCLUSIONS: The likelihood of participation in sun-protective behaviors and skin
      cancer prevention was related to a number of demographic characteristics and high
      risk behaviors, including currently smoking cigarettes and wearing seatbelts.

PMID- 11571749
TI  - Chronic lymphocytic leukemia incidence is substantially higher than estimated
      from tumor registry data.
AB  - BACKGROUND: Although chronic lymphocytic leukemia (CLL) often is described as the
      most common leukemia in the U.S. and Western Europe, to the authors' knowledge
      the true incidence of CLL in the U.S. is unknown. CLL incidence is estimated from
      tumor registry reports based on tissue pathology and cancer treatment data. Tumor
      registry data may underestimate the incidence of CLL substantially because CLL
      can be diagnosed by flow cytometric analysis of peripheral blood cells, and the
      majority of patients do not require treatment at the time of diagnosis. METHODS:
      To test the hypothesis that CLL has a higher incidence than estimated from tumor
      registry data, the authors compared the actual and reported incidence of CLL for
      a 10-year interval at the Central Arkansas Veterans Healthcare System (CAVHS).
      The accuracy of surveillance methods for new diagnoses of CLL was confirmed by
      reviewing the lymphocyte counts in 45,009 CAVHS patients over a 4-year period.
      RESULTS: The tumor registry correctly reported 58 of 93 patients with CLL (62.4%)
      who were diagnosed between January 1, 1990 and December 31, 1999. The tumor
      registry correctly reported 100% of patients with CLL diagnosed between 1990-1991
      but reported only 34.5% of patients with CLL diagnosed between 1998-1999.
      CONCLUSIONS: The incidence of CLL in the CAVHS was 37.6% higher than estimated
      from tumor registry data due to an increase in the use of peripheral blood
      immunophenotype as the only diagnostic test for CLL over the time period of the
      study. These data suggest that the true incidence of CLL may be substantially
      higher than estimated from tumor registry data.

PMID- 11571750
TI  - Epidermal growth factor receptor immunohistochemical reactivity in patients with
      American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications
      for a standardized scoring system.
AB  - BACKGROUND: An epidermal growth factor receptor (EGFR) immunohistochemical
      detection system currently is being developed. The current study attempts to
      address background EGFR reactivity issues before determining the optimum EGFR
      scoring system. METHODS: Tissue sections from 102 patients with T3N1-2M1 colon
      adenocarcinoma were stained with a prototype EGFR detection system. The number of
      cases, location, percentage, and intensity of reactive cells (0+ [none] to 3+
      [strong]) were scored and compared with the length of survival. RESULTS:
      Approximately 75.5% of the adenocarcinoma cases had EGFR reactivity; 31.4% of the
      tumors had 3+ reactivity in 10-50% of the neoplastic cells and 3.9% had 3+
      reactivity in > 50% of cells. Increased numbers of reactive cells per case
      predominantly resulted from increased 3+ reactivity. The mean percentage of 2+
      (moderate) and 3+ reactive cells per case increased in the regions of deepest
      invasion. The mean percentage of 3+ reactivity per case was significantly greater
      in the deepest tumor region compared with the superficial region (16.9% vs. 7.9%;
      P = 0.004). EGFR reactivity in metastases appeared to have the strongest
      correlation with reactivity in the deep regions of colon adenocarcinoma. An
      increasing percentage of 2+ and 3+ or 3+ only reactivity in the deep region was
      found to have the strongest correlation with decreased survival (P = 0.0252).
      CONCLUSIONS: EGFR reactivity of 2+ and 3+ may provide a framework for a scoring
      system. It may be important to evaluate EGFR reactivity in the deepest region of
      tumor invasion because this region appears to contain the largest percentage of
      3+ reactive cells and appears to have the strongest correlation with survival
      length and EGFR reactivity in lymph node and liver metastases.

PMID- 11571751
TI  - Pilot study of vitaxin--an angiogenesis inhibitor-in patients with advanced
      leiomyosarcomas.

PMID- 11571752
TI  - Isolation of a Candida glabrata homologue of RAP1, a regulator of transcription
      and telomere function in Saccharomyces cerevisiae.
AB  - To study the function of RAP1, an essential gene involved in the regulation of
      transcriptional activation, silencing and the telomere function in Saccharomyces
      cerevisiae, we isolated a Candida glabrata gene that complements the growth
      defect of a S. cerevisiae rap1 conditional mutant. The DNA sequence of the cloned
      gene, which we designated CgRAP1, predicted a 2064 bp open reading frame encoding
      a 687 amino acid protein with an overall identity of 65% and a similarity of 78%
      to Rap1p from S. cerevisiae.

PMID- 11571753
TI  - Saccharomyces cerevisiae cell wall chitin, the Kluyveromyces lactis zymocin
      receptor.
AB  - The exozymocin secreted by Kluyveromyces lactis causes sensitive yeast cells,
      including Saccharomyces cerevisiae, to arrest growth in the G(1) phase of the
      cell cycle. Despite its heterotrimeric (alpha beta gamma) structure,
      intracellular expression of its smallest subunit, the gamma-toxin, is alone
      responsible for the G(1) arrest. The alpha subunit, however, has a chitinase
      activity that is essential for holozymocin action from the cell exterior. Here we
      show that sensitive yeast cells can be rescued from zymocin treatment by
      exogenously applying crude chitin preparations, supporting the idea that chitin
      polymers can compete for binding to zymocin with chitin present on the surface of
      sensitive yeast cells. Consistent with this, holozymocin can be purified by way
      of affinity chromatography using an immobilized chitin matrix. PCR-mediated
      deletions of chitin synthesis (CHS) genes show that most, if not all, genetic
      scenarios that lead to complete loss (chs3 Delta), blocked export (chs7 Delta) or
      reduced activation (chs4 Delta), combined with mislocalization (chs4 Delta chs5
      Delta; chs4 Delta chs6 Delta; chs4 Delta chs5 Delta chs6 Delta) of chitin
      synthase III activity (CSIII), render cells refractory to the inhibitory effects
      of exozymocin. In contrast, deletions in CHS1 and CHS2, which code for CSI and
      CSII, respectively, have no effect on zymocin sensitivity. Thus, CSIII
      polymerized chitin, which amounts to almost 90% of the cell's chitin resources,
      appears to be the carbohydrate receptor required for the initial interaction of
      zymocin with sensitive cells.

PMID- 11571754
TI  - A minisatellite sequence in the upstream region of the DURA3 gene from the
      halotolerant yeast Debaryomyces hansenii.
AB  - The URA3 gene of Debaryomyces hansenii, encoding orotidine 5'-phosphate
      decarboxylase enzyme, was isolated by complementation in the yeast Saccharomyces
      cerevisiae. The deduced amino acid sequence is highly similar to Ura3 proteins
      from other yeast and fungal species. Analysis of the region upstream of the
      coding sequence revealed the presence of AG-rich minisatellite DNA sequences. In
      addition, upstream of the DURA3 sequence, we have found the 3'-terminal of a gene
      encoding a GEA2-like protein.

PMID- 11571755
TI  - Human pancreatic glucokinase (GlkB) complements the glucose signalling defect of
      Saccharomyces cerevisiae hxk2 mutants.
AB  - Human pancreatic glucokinase (GlkB, hexokinase IV) has been expressed in
      Saccharomyces cerevisiae. The recombinant protein showed similar enzyme kinetics
      to those described for the original enzyme. When expressed in hxk2 yeast mutants,
      GlkB complemented both the glucose induction and the glucose repression defects
      present in the mutant. It was also functional in regulating the activity of the
      Snf1 kinase complex in response to glucose, participating in the regulation of
      the Reg1/Glc7 phosphatase complex, as its yeast counterpart.

PMID- 11571756
TI  - The HTL1 gene (YCR020W-b) of Saccharomyces cerevisiae is necessary for growth at
      37 degrees C, and for the conservation of chromosome stability and fertility.
AB  - A small 78 codon ORF, named HTL1 (Chen et al., unpublished results), situated
      between loci MAK31 and HSP30 on chromosome III of Saccharomyces cerevisiae, is
      required for growth at 37 degrees C. In this communication, we characterize the
      ORF and show that disruption of HTL1, besides preventing growth at 37 degrees C,
      causes genetic and/or epigenetic instability at 26 degrees C: ploidy increases in
      about 10% of cells grown from individual disruptants and a fraction of disruptant
      clones are predestined to a rapid and progressive loss of fertility during growth
      at 26 degrees C.

PMID- 11571757
TI  - Graded mode of transcriptional induction in yeast pheromone signalling revealed
      by single-cell analysis.
AB  - Signalling pathways typically convert a graded, analogue signal into a binary
      cellular output. In the several eukaryotic systems that have been investigated to
      date, including MAP kinase cascade activation in Xenopus oocytes, analogue-to
      digital conversion occurs at points in the pathway between receptor activation
      and the effector mechanism. We used flow cytometry combined with an intracellular
      fluorescent reporter to examine the characteristics of the yeast pheromone
      response pathway. Surprisingly, pheromone response in yeast, which relies on the
      MAP kinase cascade, behaved in a fundamentally graded manner. Expression of
      certain exogenous dominant inhibitors of the pathway converted the response to
      graded-or-none behaviour. These results have implications for the dissection of
      biological response mechanisms in cells and illustrate how signalling pathways,
      even homologous ones, may have strikingly different signal
      propagation/amplification characteristics.

PMID- 11571758
TI  - Cloning of a fatty acid synthase component FAS1 gene from Saccharomyces kluyveri
      and its functional complementation of S. cerevisiae fas1 mutant.
AB  - A gene encoding a fatty acid synthase component, FAS1, has been cloned from a
      genomic library of the polyunsaturated fatty acid (PUFA)-producing yeast
      Saccharomyces kluyveri. This gene (named Sk-FAS1) was found to contain an open
      reading frame of 6150 bp, coding for 2049 amino acids. The deduced Sk-FAS1
      protein showed significant (75-59%) homology with FAS proteins from the other
      yeasts, including S. cerevisiae, Candida albicans and Yarrowia lipolytica. The
      substrate-binding sites of the acetyl transferase and malonyl/palmitoyl
      transferase domains, and the FMN- and NADPH-binding sites of the enoyl reductase
      domain, were all highly conserved. Expression of the Sk-FAS1 gene in S.
      cerevisiae complemented genetic disruption of the S. cerevisiae FAS1 gene (Sc
      FAS1), suggesting the formation of a heterogeneous complex of Sk-FAS1 (beta) and
      Sc-FAS2 (alpha), which is able to function to synthesize fatty acids. Compared
      with the isogenic wild-type of S. cerevisiae, as well as S. kluyveri, the S.
      cerevisiae fas1 mutant carrying the Sk-FAS1 gene showed an increase in the
      relative amount of 16-carbon fatty acids and a decrease in 18-carbon fatty acids.

PMID- 11571760
TI  - Current awareness on yeast.

PMID- 11571759
TI  - The KlCYC1 gene, a downstream region for two differentially regulated
      transcripts.
AB  - KlCYC1 encodes for cytochrome c in the yeast Kluyveromyces lactis and is
      transcribed in two mRNAs with different 3'-processing points. This is an uncommon
      transcription mechanism in yeast mRNAs. The 3' sequence encompassing the whole
      region that is needed to produce both mRNAs is analysed. We have determined
      identical processing points in K.lactis and in Saccharomyces cerevisiae cells
      transformed with KlCYC1; positions 698 and 1092 (with respect to the TAA) are the
      major polyadenylation points. This shows that the cis-elements present in the
      KlCYC1 3'-untranslated region (3'-UTR) direct a processing mechanism that has
      been conserved in yeast. In K. lactis there is a high predominance of the shorter
      transcript (1.14 kb) only at the initial logarithmic growth phase. Interestingly,
      this growth phase-dependent regulation of 3'-UTR processing is lost when the gene
      is expressed in S. cerevisiae.

PMID- 11571761
TI  - How do memory clinics compare with traditional old age psychiatry services?
AB  - METHODS: 100 consecutive referrals to the Northern Memory Clinic (NMC) were
      compared with 100 referrals to a traditional Old Age Psychiatry (OAPsych) service
      in the same city in terms of demographic variables, cognitive function (assessed
      by the Mini-Mental State Examination), and diagnosis. The study also examined the
      ability of psychometric assessments (CAMCOG, MMSE, Trail-Making Tests A & B, Word
      Fluency) and CT scans included in the NMC assessment to differentiate between
      those with and without DSM-IV dementia. RESULTS: NMC patients were significantly
      younger than OAPsych patients, had lower levels of cognitive impairment, and had
      a wider range of diagnoses. The NMC patients who were diagnosed as having
      dementia were found to be at least 2 years earlier in the course of the disease
      than those seen by the OAPsych team. The CAMCOG and MMSE were proved to be
      effective at distinguishing between patients diagnosed as dementing versus non
      dementing with cut-offs of 82/83 and 23/24 respectively, confirming previous
      findings. The Memory subscale of the CAMCOG, though much shorter, was equally as
      effective using a cut-off of 20/21. Trail-Making Tests, Word Fluency (FAS), and
      measurement of the minimum width of the medial temporal lobe (MTL) on angled CT
      scans were poor indicators of dementia in this sample. CONCLUSIONS: This study
      confirms that the memory clinic is targeting a distinct patient group compared to
      traditional old age psychiatry services, is identifying cases of dementia much
      earlier, and as such has potential to make valuable contributions to patient
      care.

PMID- 11571762
TI  - Measuring the opinions of memory clinic users: patients, relatives and general
      practitioners.
AB  - BACKGROUND: The opinions of memory clinic users are important to assess the value
      of memory clinics. OBJECTIVE: To measure the quality of care of an outpatient
      memory clinic for the elderly as perceived by patients, their relatives and
      general practitioners (GPs). METHODS: An observational study was conducted to
      measure the opinions of the users of a typical outpatient memory clinic. Opinions
      on five aspects were measured: (1) communication of the results, (2) provision of
      diagnostic information, (3) attitude of the clinicians, (4) usefulness of the
      medical assessment, and (5) information and advice to relatives. Patients and
      relatives were both interviewed with a dementia care satisfaction questionnaire.
      The GPs' opinions were derived with a self-constructed questionnaire. RESULTS: On
      105 consecutive assessments, 101 opinions of GPs, 81 of caregivers and 31 of
      patients were recorded. Positive opinions were recorded on the way the results
      were communicated, the usefulness of the assessment and attitude of the
      clinicians. In contrast to GPs and relatives, patients were less positive about
      the clarity of the diagnostic information received. Both relatives and GPs were
      negative on information and advice to relatives. CONCLUSIONS: Patients,
      caregivers and GPs had positive opinions about the diagnostic value of the memory
      clinic. Quality improvement could focus on the clarity of the diagnostic
      information for patients and on better advice to relatives.

PMID- 11571763
TI  - Galantamine: a randomized, double-blind, dose comparison in patients with
      Alzheimer's disease.
AB  - OBJECTIVES: To investigate whether Galantamine significantly improves the core
      symptoms of Alzheimer's disease (AD). BACKGROUND: Galantamine is a reversible,
      competitive, selective inhibitor of acetylcholinesterase (AChE) that also
      allosterically modulates nicotinic acetylcholine receptors. This dual mechanism
      of action provided the rationale for a phase II trial of galantamine in AD.
      METHOD: A multicentre, randomized, parallel, double-blind, placebo-controlled
      trial was carried out to evaluate the efficacy and tolerability of galantamine
      18, 24 and 36 mg/day administered for 3 months in 285 patients with mild-to
      moderate probable AD. The primary outcome measure was the Alzheimer's Disease
      Assessment Scale cognitive subscale (ADAS-cog); secondary outcome measures were
      the Clinical Global Impression of Change (CGIC) and the Progressive Deterioration
      Scale (PDS). RESULTS: Patients treated with galantamine 24 mg/day had a
      significantly better outcome than placebo on ADAS-cog; the treatment difference
      was 3 points on the intention-to-treat (ITT) analysis ( p = 0.01) and 4.2 points
      on per protocol analysis ( p = 0.001). Per protocol analysis showed that
      galantamine had a significantly better outcome than placebo on PDS ( 24-mg/day
      dose, p < 0.05) and CGIC (36-mg/day dose, p < 0.05). Galantamine was well
      tolerated at the lower doses of 18 and 24 mg/day where it produced mild,
      transient effects typical of cholinomimetic agents. CONCLUSION: This study shows
      that, relative to placebo, galantamine significantly improves the core symptoms
      of Alzheimer's disease.

PMID- 11571764
TI  - Verbal aggression in Alzheimer's disease. Clinical, functional and
      neuropsychological correlates.
AB  - OBJECTIVES: To determine the clinical, functional and neuropsychological
      correlates of verbal aggression in Alzheimer's disease in a group of consecutive
      first attendees to a memory clinic. METHODS: 150 people were evaluated and
      diagnosed as suffering with probable Alzheimer's disease. These people were
      tested using the Behave-AD for the presence of verbal aggression, delusions,
      depression and agitation. They were also assessed with cognitive, functional and
      neuropsychological scales. RESULTS: Twenty-eight per cent of this group of
      Alzheimer patients had exhibited some verbal aggression in the preceding month.
      Male gender (p = 0.022), the presence of paranoid and delusional ideation (p =
      0.003) and agitation (p = 0.042) were significantly associated with verbal
      aggression in a stepwise backward logistic regression analysis. CONCLUSION: The
      presence of verbal aggression should prompt the clinician to search for
      delusional ideation, which may respond to pharmacotherapy.

PMID- 11571765
TI  - Bupropion SR in the naturalistic treatment of elderly patients with major
      depression.
AB  - INTRODUCTION: Bupropion immediate release (IR) and bupropion sustained release
      (SR) are frequently used to treat geriatric depression, as they have few
      cardiovascular, gastrointestinal and sexual adverse effects. We sought to examine
      the efficacy and dosing patterns of bupropion in a naturalistic cohort of elderly
      subjects with major depression (MD). METHODS: 31 elderly ( > 60 years) patients
      with unipolar MD (DSM-IV) who were enrolled in Duke's Mental Health Clinical
      Research Center for the Study of Depression in Later Life were prescribed
      bupropion SR or IR, alone or in combination with other antidepressant agents, for
      12 weeks. Montgomery-Asberg depression rating scale (MADRS) scores and clinical
      global impression (CGI) severity scores were used to define response. RESULTS:
      74% (23/31) of the sample were responders (MADRS < 15) and 53% (16/30) achieved a
      partial (CGI = 2) or complete (CGI = 1) remission of MD at week 12. Among
      patients treated with bupropion SR monotherapy, the mean (range) maximal daily
      dose achieved was 240 mg (150-400 mg). Among those treated with bupropion IR, the
      mean (range) maximum daily dose achieved was 258 mg (150-450 mg). In subjects on
      monotherapy, 67% (10/15) of MD subjects were responders (MADRS < 15) and 50%
      (7/14) achieved full or partial remission. Response rates did not differ
      statistically among those with high and low medical comorbidity. CONCLUSIONS: In
      this naturalistic 12-week study, geriatric MD patients with high and low medical
      comorbidity responded well to bupropion and bupropion SR. In elderly patients,
      four to eight week acute treatment periods may be insufficient. Our findings
      suggest that nearly 50% of elderly depressed subjects at a tertiary center may
      need combination therapy over the course of their illness. Controlled randomized
      studies to establish the long-term efficacy and optimal dose of the newer
      antidepressants in geriatric depression are urgently needed.

PMID- 11571766
TI  - A short-term inpatient program for agitated demented nursing home residents.
AB  - OBJECTIVE: This case series describes the various contributors of disruptive
      behavior in demented nursing home residents and outlines the necessary steps to
      identify and treat them. DESIGN: Evaluation of overall clinical improvement and
      agitation at discharge from the hospital and at follow-up. SETTING: Nursing home
      residents consecutively admitted to the geriatric psychiatry service of a
      psychiatric university hospital in the New York metropolitan area. PATIENTS: 15
      elderly demented nursing home residents with agitation. MEASURES: Overall
      clinical improvement was assessed with the 'global assessment of functioning
      scale'. Agitation was evaluated with the 'brief agitation rating scale' and the
      'nursing home scale for agitation'. Medication side-effects were measured with
      the 'Simpson-Angus scale' and the 'abnormal involuntary movement scale'. RESULTS:
      The patients showed significantly more overall clinical improvement at discharge
      compared with admission. Additionally, agitation scores were significantly lower
      at discharge and at follow-up compared with admission. CONCLUSION: A
      comprehensive medical and neurological assessment, an accurate identification of
      comorbid psychopathology, evaluation of drug toxicity, and a thorough history of
      psychotropic medication trials are essential steps for a successful treatment.

PMID- 11571767
TI  - Markers for the functional availability of cobalamin/folate and their association
      with neuropsychiatric symptoms in the elderly.
AB  - Cobalamin/folate deficiency is common in elderly subjects and may lead to
      psychiatric symptoms, but even more often it increases the severity of other
      organic and non-organic mental diseases. This paper reviews the literature
      relevant for markers of cobalamin/folate status and their relation to
      neuropsychiatric symptoms in the elderly. Plasma homocysteine, a marker of
      cobalamin/folate status, is frequently increased in psychogeriatric patients.
      Among markers of cobalamin/folate status, plasma homocysteine shows the best
      association with neuropsychiatric dysfunction.

PMID- 11571768
TI  - To tell or not to tell-comparison of older patients' reaction to their diagnosis
      of dementia and depression.
AB  - OBJECTIVE: Investigation of the reaction of elderly patients to the disclosure of
      their diagnosis of dementia compared with depression. DESIGN: Elderly patients
      suffering from dementia and depression were asked to complete a questionnaire
      about the diagnosis and other aspects of their clinical summary sent to them by
      post. Demographic data included age, gender, marital status and occupation;
      degree of dementia or depression was established by administering the mini-mental
      state examination and the geriatric depression scale, respectively. SETTING:
      Patients were consecutive attendees of outpatient clinics (old age psychiatry)
      located in two suburban areas near London. MEASURES: Demographic data included
      age, gender, marital status and occupation; degree of dementia or depression was
      established by administering the mini-mental state examination and the geriatric
      depression scale, respectively. RESULTS: One hundred cases were recruited, 53
      with dementia and 47 with depression. Most depressed and dementia patients ( >
      75%) liked the idea of reading their diagnosis but 25% of dementia cases felt
      upset. Within the dementia group, the majority of patients with mild or severe
      dementia welcomed the idea of knowing their diagnosis; and 13 (100%) of the
      patients with vascular dementia wished to know (compared with 68% cases with
      Alzheimer's disease). None felt upset, and only 39% of them felt pessimistic
      after reading their own clinical summary. However, among dementia patients who
      also happened to be depressed, a higher proportion (60%) expressed an
      unfavourable view towards knowing their diagnosis, but only a minority (40%) of
      them were actually upset. Most older married females, especially those with
      depression and Alzheimer's disease, felt pessimistic afterwards. CONCLUSIONS:
      There was no significant difference between patients with dementia or depression
      in their wish to know their diagnosis. Patients with severe dementia, even if
      they felt upset, preferred to be told their diagnosis. Patients with vascular
      dementia tended to express a more favourable view.

PMID- 11571769
TI  - Frequency of behavioral symptoms characterizes agitation in Alzheimer's disease.
AB  - This study describes two well-characterized groups of Alzheimer's disease (AD)
      patients with similar levels of cognitive functioning, but with different overall
      behavioral disturbance levels. We sought to determine the nature of this
      difference-whether AD patients with higher levels of behavioral disturbance (n =
      148) differ from less disturbed AD patients (n = 235) in terms of (a) the range
      of symptoms exhibited, (b) the frequency of occurrence of these symptoms, or (c)
      both of these. We defined and operationalized 'diversity of behaviors' and
      'frequency' with respect to the item-level responses on the Cohen-Mansfield
      agitation inventory (CMAI). We found that, in these two samples of AD patients,
      differences occurred in the frequency of 10 out of 21 behaviors, rather than in a
      variety of endorsed behaviors. These 10 behaviors, observed at different
      frequencies in both groups, may be useful for monitoring change in studies of
      drugs or behavioral interventions for behavioral disturbance in persons with AD.

PMID- 11571770
TI  - The Psychogeriatric Assessment Scales (PAS): psychometric properties in French
      and German speaking populations.
AB  - OBJECTIVES: To investigate the structure and measurement properties of the
      Psychogeriatric Assessment Scales (PAS) in a community sample, to study the
      performance of French and German translations of the PAS, and to determine the
      power of PAS scales to discriminate dementia and depression diagnosed to DSM-IV
      criteria. Design and measures The measures were gathered as part of a large
      community survey. Responses to PAS items were obtained in the course of the
      administration of the 'Canberra Interview for the Elderly'. Demographic
      variables, the mini-mental state examination and measures of premorbid
      intelligence robust to current intellectual impairment were also gathered in the
      course of the survey. SETTING: A community survey in the cities of Zurich and
      Geneva, Switzerland. PARTICIPANTS: Subjects were residents of the two cities aged
      65 years or older. There were 465 participants from Zurich and 456 from Geneva.
      Interviews with an informant who knew the subject well were also obtained.
      Subjects from Zurich were interviewed in German, subjects from Geneva in French.
      RESULTS: Confirmatory factor analyses of PAS scales showed close agreement
      between sites and with results obtained in the sample used to construct the
      instrument. Correlations with demographic and validating variables also showed
      this pattern. The PAS cognitive impairment and cognitive decline scales were
      shown to be good discriminators of DSM-IV dementia while the depression scale
      discriminated DSM-IV major depressive episode. CONCLUSIONS: This study supports
      the PAS as a valid and reliable summary of the status of older persons with
      respect to the impairments, changes and symptomatology that lie at the core of
      dementing and depressive disorders. This study not only supports the results
      found in the original development sample, but demonstrates that it performs well
      against DSM-IV diagnostic criteria and amongst speakers of French and German.

PMID- 11571771
TI  - Psychotropic drug use in elderly people with and without dementia.
AB  - OBJECTIVE: To determine the prevalence of psychotropic drug use in very old
      persons with and without dementia in two time periods, and describe the patterns
      of psychotropic drug use between institutions and non-institutions. METHODS:
      Descriptive analysis on a sample of subjects aged 81+ from a population-based
      study in Stockholm, Sweden. Psychotropic drug use data were collected from the
      1987-1989 and 1994-1996 periods of the study. The diagnosis of dementia was based
      on the DSM III-R. RESULTS: About 41% of the subjects used at least one
      psychotropic drug in both periods. Women and subjects in institutions more
      commonly used psychotropic drugs. The most commonly reported were, in rank order,
      hypnotics-sedatives, anxiolytics, antipsychotics and antidepressants. Hypnotics
      sedatives and anxiolytics were the most commonly used in both institutions and
      non-institutions. More persons with dementia used psychotropic drugs in both
      periods. The use of newer drugs, for example, SSRI, was evident. Multivariate
      analyses showed increased risk for psychotropic drug use among subjects in
      institutions. CONCLUSIONS: This study confirms the high rate of psychotropic drug
      use in the very old, particularly in persons with dementia. Psychotropic drug use
      was high among subjects living in institutions.

PMID- 11571772
TI  - Extrapyramidal signs and cognitive abilities in Alzheimer's disease.
AB  - OBJECTIVE: To evaluate whether the relationship between extrapyramidal signs
      (EPS) and cognitive disturbances in Alzheimer's disease (AD) is influenced by
      illness duration. METHODS: A multivariate regression analysis was used to study
      the relationships between EPS, illness duration and five cognitive ability areas
      based on the Mattis Dementia Rating Scale (DRS) in 89 clinically diagnosed AD
      patients with extrapyramidal motor involvement. RESULTS: Severity of EPS was
      statistically associated with performance on four cognitive ability areas from
      the DRS including: attention, initiation and perseveration, construction and
      memory. Age was a significant factor related to severity of EPS. However illness
      duration did not contribute to the strength of the association between EPS and
      cognitive disturbances in patients with AD. CONCLUSIONS: The findings of the
      present study support the notion that while neuropsychological and motor
      functions often coexist in patients with AD, their relationship seems to be
      unrelated to degenerative processes that accumulate throughout the illness.

PMID- 11571773
TI  - Diagnosis of dementia from the history and aetiology schedule.
AB  - OBJECTIVE: To provide a computerised method of diagnosing organic brain syndrome
      from history data without the use of mental state data. METHODS: Interview
      dataset from participants in a community study of the incidence of dementia was
      used to form a training sample and validation sample. The algorithm was developed
      on the training sample and tested on the validation sample. RESULTS: Performance
      in the training and validation samples was very similar. The algorithm shows
      monotonically increasing probability of being diagnosed with dementia as a
      function of the proposed level of diagnostic confidence. At the proposed cut
      point it has sensitivity 94% and specificity 84% for detecting concurrent
      psychiatrist's diagnosis of dementia. CONCLUSIONS: The method provides a good
      agreement with psychiatrist's diagnosis, and the results in the validation sample
      show little shrinkage. The method will prove useful in studies where it has
      proved impossible to collect mental state information on all the study
      participants.

PMID- 11571774
TI  - Anthropometric risk factors in Alzheimer's disease.

PMID- 11571775
TI  - Response to ECT in depressed, demented patients; possible role of apolipoprotein
      E(4) as response marker.

PMID- 11571776
TI  - Suicide rates among the elderly in different religious cultures.

PMID- 11571778
TI  - Current awareness in geriatric psychiatry. Bibliography.
AB  - In order to keep subscribers up-to-date with the latest developments in their
      field, John Wiley &amp: Sons are providing a current awareness service in each
      issue of the journal. The bibliography contains newly published material in the
      field of geriatric psychiatry. Each bibliography is divided into 9 sections: 1
      Books, Reviews &amp: Symposia; 2 General; 3 Assessment; 4 Epidemiology; 5
      Therapy; 6 Care; 7 Dementia; 8 Depression; 9 Psychology. Within each section,
      articles are listed in alphabetical order with respect to author. If, in the
      preceding period, no publications are located relevant to any one of these
      headings, that section will be omitted

PMID- 11571779
TI  - KUB3 amplification and overexpression in human gliomas.
AB  - Gene amplification is known to occur frequently in human glioma. Recently we
      reported cloning of a novel gene termed glioma-amplified sequence 16 (GAS16) by
      microdissection-mediated cDNA capture. In this article, we demonstrate that GAS16
      results from an alternative splicing process of the Ku70 binding protein 3 (KUB3)
      that is essential for DNA double-strand break repair. The alternative splice
      product was found in glioblastoma and in normal fetal brain. We determined the
      amplification frequency of KUB3 in glioma with different grading. We analyzed a
      total of 102 glioma primary tumors and found KUB3 to be amplified in 12/82 (14%)
      glioblastomas, 4/13 anaplastic astrocytomas (30%), and 2/4 astrocytomas, but in
      none of three pilocytic astrocytomas. Northern blot analysis of glioblastoma
      shows a strong correlation between KUB3 amplification and overexpression.
      Amplification of KUB3 appears to be independent of other genetic changes
      frequently associated with the development of gliomas, including EGFR
      amplification, LOH of TP53, and LOH of chromosome 10. The KUB3 amplification and
      overexpression may interfere with the function of KUB3 in the DNA-PK complex
      involved in the maintenance of genome stability and reduction of mutation
      frequency.

PMID- 11571781
TI  - Inhibition of store-operated Ca(2+) influx by acidic extracellular pH in cultured
      human microglia.
AB  - The effects of extracellular acidification on Ca(2+)-dependent signaling pathways
      in human microglia were investigated using Ca(2+)-sensitive fluorescence
      microscopy. Adenosine triphosphate (ATP) was used to elicit Ca(2+) responses
      primarily dependent on the depletion of intracellular endoplasmic reticulum (ER)
      stores, while platelet-activating factor (PAF) was used to elicit responses
      primarily dependent on store-operated channel (SOC) influx of Ca(2+). The
      duration of transient responses induced by ATP was not significantly different in
      standard physiological pH 7.4 (mean duration 30.2 +/- 2.5 s) or acidified pH 6.2
      (mean duration 31.7 +/- 2.8 s) extracellular solutions. However, the time course
      of the PAF response at pH 7.4 was significantly reduced by 87% with external pH
      at 6.2. These results suggest that acidification of extracellular solutions
      inhibits SOC entry of Ca(2+) with little or no effect on depletion of ER stores.
      Changes of extracellular pH over the range from 8.6 to 6.2 during the development
      of a sustained SOC influx induced by PAF resulted in instantaneous modulation of
      SOC amplitude indicating a rapidly reversible effect of pH on this Ca(2+)
      pathway. Whole-cell patch clamp recordings showed external acidification blocked
      depolarization-activated outward K(+) current indicating cellular depolarization
      may be involved in the acid pH inhibition. Since SOC mediated influx of Ca(2+) is
      strongly modulated by membrane potential, the electrophysiological data suggest
      that acidification may act to inhibit SOC by cellular depolarization. These
      results suggest that acidification observed during cerebral ischemia may alter
      microglial responses and functions.

PMID- 11571780
TI  - Distribution of P2X receptors on astrocytes in juvenile rat hippocampus.
AB  - Recent evidence suggested that ATP acting via ionotropic (P2X) and metabotropic
      (P2Y) purinergic receptors might be involved in signaling between glial cells and
      within glial-neuronal networks. In contrast to their neuronal counterpart, the
      identity of P2X receptors in CNS glial cells is largely unknown. In the present
      study, antibodies recognizing the subunits P2X1-P2X7 were applied together with
      the astroglial marker S100beta and nuclear labeling with Hoechst 33342 to
      investigate semiquantitatively the distribution of the whole set of P2X receptors
      in astrocytes of the juvenile rat hippocampus. Expression of P2X1-P2X4, P2X6, and
      P2X7 subunits was observed in astrocytes of various hippocampal subregions, but
      the cells were completely devoid of P2X5 protein. S100beta-positive cells
      expressing subunits P2X3-P2X7 occurred evenly in the different subfields, while
      P2X1- and P2X2-positive astrocytes were distributed more heterogeneously. The
      staining pattern of P2X subunits also differed at the subcellular level.
      Antibodies against P2X2 and P2X4 labeled both astroglial cell bodies and
      processes. Immunoreactivity for P2X1 and P2X6 was mainly confined to somatic
      areas of S100beta-positive cells, whereas the subunit P2X3 was primarily
      localized along astroglial processes. Knowledge of the distribution of P2X
      receptors might provide a basis for a better understanding of their specific role
      in cell-cell signaling.

PMID- 11571782
TI  - SpL201: a conditionally immortalized Schwann cell precursor line that generates
      myelin.
AB  - Dramatic progress has been made over recent years toward the elucidation of the
      mechanisms regulating lineage determination and cell survival in the developing
      peripheral nervous system. However, our understanding of Schwann cell development
      is limited. This is partly due to the difficulties in culturing primary Schwann
      cell precursor cells, the earliest developmental stage of the Schwann cell
      lineage defined to date. Both the inability to maintain cultured Schwann cell
      precursor cells in an undifferentiated state and the technical difficulties
      involved in their isolation have hampered progress. We have conditionally
      immortalized rat Schwann cell precursor cells using a retrovirally encoded
      EGFR/neu fusion protein to circumvent these problems and to generate a source of
      homogeneous cells. The resulting SpL201 cell line expresses p75 and nestin, two
      proteins expressed by neural crest-derived cells, as well as peripheral myelin
      protein 22, protein zero, and Oct-6 as markers of the Schwann cell lineage. When
      cultured in EGF-containing medium, the SpL201 cells proliferate and maintain an
      undifferentiated, Schwann cell precursor cell-like state. The cell line is
      dependent on EGF for survival but can differentiate into early Schwann cell-like
      cells in response to exogenous factors. Like primary rat Schwann cells, SpL201
      cells upregulate Oct-6 and myelin gene expression in response to forskolin
      treatment. Furthermore, the SpL201 cell line can form myelin in the presence of
      axons in vitro and is capable of extensively remyelinating a CNS white matter
      lesion in vivo. Thus, this cell line provides a valuable and unique tool to study
      the Schwann cell lineage, including differentiation from the Schwann cell
      precursor cell stage through to myelination.

PMID- 11571783
TI  - A role for oligodendrocyte-derived IGF-1 in trophic support of cortical neurons.
AB  - Neurons and glia interact in the development of mammalian central nervous systems
      and in the maintenance of stable myelinated axons. Recent evidence suggests a
      role for oligodendrocytes in providing trophic support for neurons during
      development and in the mature nervous system. This work prompted us to study
      oligodendrocyte influences on neuronal survival and death in vitro. Rat embryonic
      cortical neurons were co-cultured with purified oligodendrocytes at different
      developmental stages and separately with oligodendrocyte-conditioned medium.
      Neuronal survival was measured by immunocytochemistry and 3H-GABA uptake. Neurons
      show a marked increase in survival when co-cultured directly with oligodendrocyte
      precursors (OPCs) and differentiated oligodendrocytes. Neurons cultured in the
      presence of OPCs separated by a permeable membrane and those cultured in medium
      conditioned by oligodendrocytes also show a significant increase in survival.
      Medium conditioned by differentiated oligodendrocytes provides a greater survival
      effect than medium conditioned by OPCs. Neutralising antibodies to IGF-1, but not
      to other candidate trophic factors, block the soluble survival effect of
      oligodendrocytes. Cells of the oligodendrocyte lineage produce IGF-1 and
      recombinant IGF-1 promotes neuronal survival under identical conditions. This
      study provides evidence that OPCs and differentiated oligodendrocytes support
      neuronal survival by both contact-mediated and soluble mechanisms and that IGF-1
      significantly contributes to this effect.

PMID- 11571784
TI  - Sublytic C5b-9-stimulated Schwann cell survival through PI 3-kinase-mediated
      phosphorylation of BAD.
AB  - Sublytic C5b-9 induces cell cycle activation, proliferation, and rescue from
      apoptosis in Schwann cells. The signaling pathways for C5b-9-mediated rescue were
      investigated. Following serum withdrawal, DNA fragmentation, detected by TUNEL
      and FACS analysis, was 56.7% +/- 7.3 and 91.9% +/- 2.4 in cultured sciatic nerve
      Schwann cells from 6-day-old rats after 18 h and 24 h, respectively. Apoptosis
      was confirmed by inhibition of DNA fragmentation in a dose-dependent manner by
      DMQD-CHO, a caspase-3 inhibitor. Treatment with sublytic C5b-9 generated with
      purified components (C5*9) or Ab+C7-depleted serum (C7dHS)+C7 rescued 89% and 86%
      of Schwann cells, respectively, as compared with cells treated with C5*6, C8, C9,
      or Ab+C7dHS. Sublytic C5b-9 increased Schwann cell PI-3 kinase and Akt activity
      maximally at 5 min 3.14 +/- 0.5-fold and 3.56 +/- 0.4-fold, respectively, over
      controls. ERK-1 activity was maximally stimulated 2.98-fold at 15 min. Inhibition
      of PI-3 kinase by LY294002 abrogated the C5b-9-mediated Schwann cell rescue from
      apoptosis, while inhibition of ERK-1 with PD098,059 did not. PI-3 kinase-Akt
      pathway activation by C5b-9 induced, within 15 min, a 6.34 +/- 1.2-fold increase
      in BAD phosphorylation at Ser 136, but not at Ser 112. Downstream Bcl-x(L)
      protein was increased 2.61-fold +/- 0.34-fold by 18 h and 3.9-fold +/- 0.84-fold
      by 24 h over controls. LY294002 prevented both BAD phosphorylation at Ser 136 and
      Bcl-x(L) protein induction, while PD098,059 did not. Our data indicated that
      sublytic C5b-9 rescued Schwann cell from apoptosis via activation of PI-3 kinase
      Akt, BAD phosphorylation on Ser 136 and increased expression of Bcl-x(L).
      Sublytic C5b-9 detected on Schwann cell in vivo during inflammatory neuropathy
      may facilitate survival of Schwann cell capable of remyelination.

PMID- 11571785
TI  - Upregulation of transcription factors controlling MHC expression in multiple
      sclerosis lesions.
AB  - The expression of major histocompatibility complex (MHC) class I and class II in
      the CNS has received considerable interest because of its importance in
      neurodegenerative or inflammatory diseases, such as multiple sclerosis (MS).
      However, at the moment nothing is known about the expression patterns of
      transcription factors controlling MHC expression in MS lesions. Here, we
      performed an extensive immunohistochemical analysis on MS affected postmortem
      brain tissue to determine the cellular localization and distribution of different
      MHC-controlling transcription factors. We show that phagocytic macrophages in
      active demyelinating MS lesions displayed a moderate to strong immunostaining of
      the MHC-specific transcription factors RFX and CIITA, as well as the general
      transcription factors NF-kappaB, IRF1, STAT1, USF, and CREB, which was congruent
      with a strongly enhanced expression of HLA-DR, HLA-DQ, HLA-DP, and HLA class I.
      In the normal-appearing white matter (NAWM), clusters of activated microglial
      cells forming preactive lesions displayed an overall stronger expression level of
      these transcription factors, combined with a strong to intense level of MHC class
      I and class II immunostaining. In general, astrocytes and oligodendrocytes either
      did not express, or weakly expressed, these transcription factors, correlating
      with a lack of MHC class II and weak MHC class I expression. Together, the
      elevated expression level of transcription factors governing expression of MHC
      class I and class II molecules in activated microglial cells and phagocytic
      macrophages strongly suggests a general state of microglial cell activation in MS
      lesions.

PMID- 11571787
TI  - Developmental changes of tau protein and mRNA in cultured rat brain
      oligodendrocytes.
AB  - Oligodendrocytes elaborate an extensive network of multibranched processes and
      flat membranous sheets. Microtubules (MT) participate in the elaboration and
      stabilization of myelin-forming processes and are essential for cellular sorting
      processes. Microtubule-associated proteins (MAPs) are involved in the regulation
      and stabilization of the dynamic MT network. It has been shown previously that
      oligodendrocytes express the MAP tau, a phosphoprotein most abundant in neurons
      of the CNS. In this article, we demonstrate for the first time that
      oligodendrocytes contain all six tau isoforms, and that tau mRNA and protein
      expression is developmentally regulated. Immunoblot analysis reveals that tau
      protein is more abundant, and mature isoforms are more prominent at later stages
      of development. During the first week of culture maturation, a marked decrease in
      phosphorylation is observable. Using an RT-PCR approach, we can show that
      oligodendrocytes express small amounts of exon 3 containing isoforms and that
      during culture maturation, tau mRNA splice products with 3 MT-binding domains
      (3R) decrease and mRNA with 4 MT-binding domains (4R) increase. In situ
      hybridization study demonstrates that tau mRNA is present in precursor cells and
      in mature oligodendrocytes. Tau mRNA is actively transported into the cellular
      processes, is specifically present in the primary and some of the secondary
      processes, enriched at the turning and branching points and the growing tips, and
      often appears as small patches. Hence, localized tau translation at specific
      sites in the cellular extensions might contribute to the regulation of MT
      stability during process formation, early axonal contact establishment, and
      myelination.

PMID- 11571789
TI  - [Mapping of the human genome is only the beginning. The next big step is the
      development of pharmacogenetics].

PMID- 11571786
TI  - Opioid system diversity in developing neurons, astroglia, and oligodendroglia in
      the subventricular zone and striatum: impact on gliogenesis in vivo.
AB  - Accumulating evidence, obtained largely in vitro, indicates that opioids regulate
      the genesis of neurons and glia and their precursors in the nervous system.
      Despite this evidence, few studies have assessed opioid receptor expression in
      identified cells within germinal zones or examined opioid effects on gliogenesis
      in vivo. To address this question, the role of opioids was explored in the
      subventricular zone (SVZ) and/or striatum of 2-5-day-old and/or adult ICR mice.
      The results showed that subpopulations of neurons, astrocytes, and
      oligodendrocytes in the SVZ and striatum differentially express mu-, delta-,
      and/or kappa-receptor immunoreactivity in a cell type-specific and
      developmentally regulated manner. In addition, DNA synthesis was assessed by
      examining 5-bromo-2'-deoxyuridine (BrdU) incorporation into glial and nonglial
      precursors. Morphine (a preferential mu-agonist) significantly decreased the
      number of BrdU-labeled GFAP(+) cells compared with controls or mice co-treated
      with naltrexone plus morphine. Alternatively, in S100beta(+) cells, morphine did
      not significantly decrease BrdU incorporation; however, significant differences
      were noted between mice treated with morphine and those treated with morphine
      plus naltrexone. Most cells were GFAP(-)/S100beta(-). When BrdU incorporation was
      assessed within the total population (glia and nonglia), morphine had no net
      effect, but naltrexone alone markedly increased BrdU incorporation. This finding
      suggests that DNA synthesis in GFAP(-)/S100beta(-) cells is tonically suppressed
      by endogenous opioids. Assuming that S100beta and GFAP, respectively, distinguish
      among younger and older astroglia, this implies that astroglial replication
      becomes increasingly sensitive to morphine during maturation, and suggests that
      opioids differentially regulate the development of distinct subpopulations of
      glia and glial precursors.

PMID- 11571790
TI  - [Better catheters wanted! Great possibility for product development].

PMID- 11571791
TI  - [Infection a dreaded central venous catheter-related complication. A reminder of
      the significance of good aseptics is justified].
AB  - The use of central venous catheters has increased markedly. Large numbers of
      patients are therefore at risk for catheter-related infections. This paper
      reviews the literature on prevention of intravascular catheter-related
      complications. Microbes colonising the catheter hubs and the skin around the
      insertion site are the source of most of these infections. By simple routines it
      is possible to reduce the risk for microbial spread from these sites to the
      bloodstream.

PMID- 11571788
TI  - Rapid morphological changes in astrocytes are accompanied by redistribution but
      not by quantitative changes of cytoskeletal proteins.
AB  - Astrocytes have the potential to acquire very different morphologies, depending
      on their regional location in the CNS and on their functional interactions with
      other cell types. Morphological changes between a flat or a fibroblast-like and a
      stellate or process-bearing appearance, and vice versa, can occur rapidly, but
      very little is known as to whether morphological transformations are based on
      quantitative changes of cytoskeletal proteins in microfilaments, intermediate
      filaments, and/or microtubules. Using a cell culture of selective type 1
      astrocytes, we compared the distribution and protein amounts of a number of
      cytoskeletal proteins both during primary process growth induced by specific
      media conditions and after secondary transformations induced by dBcAMP. Our data
      presented in this report support the idea that astrocytes can undergo dramatic
      changes in their morphology requiring subcellular redistribution of most
      cytoskeletal proteins but no quantitative modifications of the amount of the
      respective proteins. After pharmacological treatment with lysophosphatic acid and
      genistein we show that astrocytes can acquire intermediate morphologies
      reminiscent of both fibroblast and stellate-like cells. These experiments
      demonstrate that the recently described RhoA-mediated signaling cascade between
      the cell surface and cytoskeletal proteins is only one of several signaling
      pathways acting on the astrocytic cytoskeleton.

PMID- 11571792
TI  - [Ethical aspects of stem cell research. Legislation and guidelines in Europe].
AB  - Research on different types of stem cells is of major interest because of its
      apparent very promising therapeutic prospects, such as for Parkinson's and
      Alzheimer's disease, spinal cord injuries, stroke, diabetes, cardiac failure,
      liver failure, cartilage injuries, severe blood diseases, cancer etc. Stem cells
      can be derived from different sources: adult tissue, foetal tissues, and from in
      vitro fertilised embryos. Depending on their origin they have varying capacity to
      multiply and differentiate to other cell types. It is at present not possible to
      predict which types of cells will be best suitable for various therapeutic
      situations. Embryonic stem cells have been shown capable of differentiating into
      all the different tissues and cell types of the body, but they cannot form a new
      individual. Because of the ethics question involved, The European Group on Ethics
      on Science and New Technologies for the European Commission and Parliament (EGE),
      and the Ethics Committee of the Nordic Council of Ministers have prepared reports
      and given guidelines for research on stem cells. According to the guidelines,
      every country should regulate the research. Only embryos, which cannot be used in
      infertility treatment, and have been donated for research, can be used. Creation
      of embryos solely for research purposes, including somatic cell nuclear transfer,
      is not regarded as acceptable for the time being. Both partners of the donating
      couple have to sign an informed consent document. Ongoing research in Sweden is
      well in line with these European and Nordic recommendations.

PMID- 11571793
TI  - [Check your waist circumference! Overweight, obesity and abdominal obesity risk
      factors of type 2 diabetes].
AB  - The object with the present study was to present prevalence data in a rural area
      in Sweden regarding overweight, obesity and abdominal obesity presented by waist
      circumference. The study was population-based in primary health care. The target
      group was aged 20 years or more. A total of 91% (n = 6,686) participated. 45% of
      men and 32% of women were overweight (BMI 25-29.9 kg/m2), 12% of men and 17% of
      women were obese (BMI > or = 30 kg/m2). The programme found among men 25.8% with
      a waist circumference 94-101.9 cm and 18.0% > or = 102 cm and among women 22.7%
      with 80.0-87.9 cm and 27.2% > or = 88 cm. The relative risk for type 2 diabetes
      increased with waist circumference. Making health care personnel and patients
      aware of overweight, obesity and abdominal obesity and the risk of associated
      diseases and encourage a healthy life style is urgent in time of an obesity
      epidemic.

PMID- 11571794
TI  - [Serotonin uptake inhibitors provide rapid relief from premenstrual dysphoria.
      New findings shed light on how serotonin modulates sex hormone-related behavior].
AB  - Premenstrual dysphoria (PMD) is a severe form of premenstrual syndrome,
      afflicting 5-10% of all women. The cardinal symptom--surfacing between ovulation
      and menstruation, and disappearing within a few days after the onset of the
      bleeding--is irritability. Serotonin reuptake inhibitors (SRIs), but not non
      serotonergic antidepressants, reduce the symptoms of PMD very effectively. Since
      the, onset of action of SRIs is rapid when used for PMD, medication may be
      restricted to the luteal phase. The finding that SRIs are effective for PMD lends
      support for the hypothesis that a major role for brain serotonin is to modulate
      sex steroid-driven behavior.

PMID- 11571795
TI  - [Harmonization of dementia diagnoses--a necessary quality assurance].
AB  - Classification and registration of diseases is necessary in order to monitor the
      proliferation of diseases in a population. Despite the presence of an
      international framework for classification of diseases (ICD 10) which has been
      approved by the Swedish authorities, the guidelines provided are not observed in
      the area of dementia diseases. Different diagnoses can be used to describe the
      same condition, and "dementia unspecified" is sometimes employed when a specified
      diagnosis could have been used. In order to refine consensus regarding the use of
      different diagnoses in the dementia field, representatives for the Swedish
      University hospitals and medical faculties propose a unified description of a
      limited number of dementia diagnoses.

PMID- 11571796
TI  - [Celiac disease can be associated with severe neurological symptoms. Analysis of
      gliadin antibodies should be considered in suspected cases].
AB  - Celiac disease can be associated with a wide spectrum of neurological and
      psychiatric symptoms (cerebellar ataxia, neuromuscular manifestations, epilepsy,
      dementia), even in the absence of malabsorption or gastrointestinal symptoms. The
      case of a 72-year-old man with a rapidly progressive, lethal encephalopathy
      secondary to celiac disease is reported, together with a review of documented
      neurological symptoms in celiac disease. The aetiology of these neurological
      symptoms is unknown, although immunological mechanisms are suspected.

PMID- 11571797
TI  - [Extensive outbreak of tuberculosis among pupils in an English school. Can it hit
      Sweden, too?].

PMID- 11571798
TI  - [Rheumatic fever behind acute chorea in a young girl. A case report].
AB  - This article presents the case of a 13-year old girl who was admitted to the
      emergency department because of rapidly evolving, seriously disabling impairments
      in movement and speech. Investigation led to the conclusion that her problems
      were caused by Sydenham's chorea as a manifestation of rheumatic fever. A
      neuropsychiatric examination performed one year after the onset of disease
      revealed a hitherto unknown mild mental retardation. The case description is
      followed by a clinical update on rheumatic fever focusing on cerebral
      manifestations. The theories concerning the existence of PANDAS--an autoimmune
      neuropsychiatric disorder following streptococcal infections, distinct from
      rheumatic fever--are presented.

PMID- 11571799
TI  - [Intercession and healing. Religious content of the intercession gives strength
      to change].

PMID- 11571800
TI  - [The majority of medical students are positive to emergency medicine as a
      specialty].

PMID- 11571801
TI  - [The American emergency room--myths and facts].

PMID- 11571802
TI  - [There are obese men in art, too].

PMID- 11571803
TI  - [Unbalanced medical research].

PMID- 11571804
TI  - [Boycott or publish].

PMID- 11571805
TI  - [Immunologic errors].

PMID- 11571806
TI  - [Negative sweating].

PMID- 11571807
TI  - Cerivastatin withdrawn from market.

PMID- 11571809
TI  - Florida's lethal-injection process involves pharmacist.

PMID- 11571808
TI  - Immunization campaign targets influenza, meningitis, tetanus.

PMID- 11571810
TI  - Telemedicine offers new way to manage asthma.

PMID- 11571811
TI  - Secondary wholesalers oppose FDA pedigree regulation.

PMID- 11571812
TI  - Consumer group says drug manufacturers exaggerate R&D expenses.

PMID- 11571813
TI  - Recognition, pathophysiology, and management of acute myocardial infarction.
AB  - New insights into the pathophysiology of atherosclerotic plaques leading to acute
      myocardial infarction (MI) are discussed, along with new diagnostic and treatment
      strategies. Ischemic heart disease represents a continuum from stable angina to
      unstable angina to non-Q-wave MI to Q-wave MI. Patients whose angina becomes
      unstable are classified as having acute coronary syndrome (ACS). It was formerly
      believed that thrombosis leading to critical occlusion of coronary arteries at
      the site of atherosclerotic plaque rupture was the common cause of ischemic heart
      disease. It is now thought that even lesions that do not critically occlude
      coronary arteries can cause MI. ACS can be caused by the rupture of an unstable
      atherosclerotic plaque. Vulnerable plaques are usually those causing only mild to
      moderate stenosis and having a lipid-rich core and a thin, macrophage-dense,
      collagen-poor fibrous cap. Factors affecting plaque rupture include mechanical
      injury, circadian rhythm, inflammation, and infection. Progressive thrombosis and
      vasospasm may follow plaque rupture. The diagnosis of MI starts with the
      recognition of symptoms of myocardial ischemia that are new or different from the
      usual pattern. Agents used to prevent or treat plaque rupture and its
      complications include thrombolytics, antiplatelet agents, antithrombotics, beta
      blockers, angiotensin-converting-enzyme (ACE) inhibitors, and nitrates. Once
      patients survive the acute phase of MI, long-term therapy for prevention of
      future events begins. Post-MI patients should receive aspirin, beta-blockers, and
      an ACE inhibitor indefinitely; modification of cardiovascular risk factors is
      also important. Greater understanding of the pathophysiology of ACS has led to
      strategies to limit the progression of atherosclerosis and to improve survival
      and function after an acute event.

PMID- 11571814
TI  - Program to remove incorrect allergy documentation in pediatrics medical records.
AB  - The incidence of incorrectly reported drug allergies in a pediatrics hospital and
      the effectiveness of pharmacist interventions to clarify these reports were
      studied. A four-month prospective study included children (< or = 18 years of
      age) with at least one drug allergy reported in their medical chart. Drug
      allergies were assessed by a pharmacist who labeled the reactions as true,
      incorrectly reported, or undetermined allergies, in accordance with defined
      criteria. When an incorrectly reported allergy was removed from a patient's chart
      with the consent of the attending physician, the intervention was reported to the
      community pharmacist. A total of 186 of 248 drug allergies identified in 1591
      patient charts were challenged. Of these, 26 (14%), 103 (55%), and 57 (31%) were
      considered true, undetermined, and incorrectly reported drug allergies,
      respectively, by the pharmacist. A total of 53 (93%) incorrectly reported
      allergies were removed from patients' charts with the consent of the attending
      physicians. Community pharmacists were contacted in 25 of these cases. At follow
      up, the incorrect allergy documentation was found to have been removed from 23
      community pharmacy charts. A pharmacist found numerous incorrectly reported
      allergies in a pediatrics hospital and assisted in removing them from patients'
      medical charts.

PMID- 11571815
TI  - Opportunities for improving the quality of hypertension care in a managed care
      setting.
AB  - Hypertension management practices and patient health outcomes in a managed care
      setting were evaluated. Health-system pharmacists analyzed plan medical and
      pharmacy claims data for September 1, 1998, to August 31, 1999, to identify
      hypertensive enrollees (n = 23,316). Reviews of pharmacy claims and medical
      charts of a sample of hypertensive patients (n = 374) determined blood pressure
      control status, prevalence of cardiovascular risk factors, and comorbidities. The
      majority of patients treated for hypertension (66%) did not achieve blood
      pressure control. Analysis revealed a high prevalence of cardiovascular risk
      factors among hypertensive patients, with 92.2% of study patients having two or
      more risk factors. Reviews of 132,512 pharmacy claims revealed that one half of
      all prescribed therapies were for monotherapy, and 21% of hypertensive patients
      were prescribed combination therapy with two different agents. Data from a large
      managed care organization revealed that more than half of all hypertensive
      patients had inadequate blood pressure control. A quality improvement program for
      hypertension care that can improve patient health outcomes must educate patients
      and health care providers about the implications of the disease, identify
      patients with compelling comorbidities, evaluate pharmacologic regimens, and
      recommend therapeutic changes when necessary.

PMID- 11571816
TI  - Effect of pravastatin-to-simvastatin conversion on low-density-lipoprotein
      cholesterol.
AB  - The effects of a pravastatin-to-simvastatin conversion program on low-density
      lipoprotein (LDL) cholesterol levels were studied. Patients receiving pravastatin
      at a Veterans Affairs medical center were switched to simvastatin beginning in
      1997. The dosage of simvastatin was based on the additional percent reduction in
      LDL cholesterol needed to achieve the goal specified by the National Cholesterol
      Education Program. The primary endpoint was the change in the percentage of
      patients meeting their LDL cholesterol goal at baseline and follow-up. Changes in
      lipid indices, the relative risk (RR) of coronary heart disease (CHD), and
      program costs were also evaluated. A total of 1032 patients completed the
      program. The mean +/- S.D. daily doses of pravastatin and simvastatin were 25.2
      +/- 11.3 and 22.7 +/- 13.3 mg, respectively. Median baseline and follow-up LDL
      cholesterol concentrations were 116 and 99 mg/dL, respectively (p < 0.001).
      Overall, 44% of the patients met their LDL cholesterol goal while taking
      pravastatin, compared with 69% after conversion to simvastatin (p < 0.001). The
      predicted mean RR of a future CHD event (based on changes in serum lipids) was
      0.87 (95% confidence interval, 0.83-0.91) four years after conversion. The total
      cost of the program was $40,644 in the first year, and there was a net saving
      thereafter. Therapeutic interchange between pravastatin and simvastatin increased
      the number of patients meeting their LDL cholesterol goal.

PMID- 11571818
TI  - Pharmacy costs associated with nonformulary drug requests.
AB  - Pharmacy costs associated with handling nonformulary drug requests were studied.
      Data for all nonformulary drug orders received at a university hospital between
      August 1 and October 31, 1999, were evaluated to determine their outcome and the
      cost differential between the nonformulary drug and formulary alternative. Two
      sets of data were used to analyze medication costs: data from nonformulary
      medication request forms, which allowed the cost of nonformulary drugs and their
      formulary alternatives to be calculated, and data from the pharmacy computer
      system, which enabled actual nonformulary drug use to be captured. Labor costs
      associated with processing these requests were determined through time analysis,
      which included the potential for orders to be received at different times of the
      day and with different levels of technician and pharmacist support. Economic
      analysis revealed that the greatest cost saving occurred when converting
      nonformulary injectable products to formulary alternatives. Interventions were
      least costly during normal business hours, when all the satellite pharmacies were
      open and fully staffed. Pharmacists' interventions in oral product orders
      resulted in a net increase in expenditures. Incremental pharmacy costs associated
      with processing nonformulary medication requests in an inpatient setting are
      greater than the drug acquisition cost saving for most agents, particularly oral
      medications.

PMID- 11571817
TI  - Comparison of therapeutic interchange with standard educational tools for
      influencing fluoroquinolone prescribing.
AB  - The abilities of therapeutic interchange (TI) and standard educational tools
      (SET) to change prescribing habits were compared. We evaluated the replacement of
      ciprofloxacin with levofloxacin in a four-hospital health system during a 14
      month study period. Two hospitals used TI and two SET. The demographics, sites of
      infection, and severity of illness were analyzed for 554 patients treated at SET
      hospitals and 1323 patients treated at TI hospitals during a total of 2040
      hospitalizations over a 14-month period. In TI hospitals, 97% of patients
      received levofloxacin, whereas 43% received levofloxacin in SET hospitals (p <
      0.001). Clinical outcomes were not significantly different for the two groups,
      although more patients in the SET hospitals received combination antimicrobial
      therapy. Differences in savings per patient were significant between TI hospitals
      ($60) and SET hospitals ($37) (p < 0.001). The total annualized savings for all
      four hospitals was $156,444. TI was more effective than SET in facilitating
      changes in prescribing patterns in a health care system and resulted in
      significant cost savings to hospitals and payers.

PMID- 11571819
TI  - Stability and compatibility of methylprednisolone acetate and ropivacaine
      hydrochloride in polypropylene syringes for epidural administration.

PMID- 11571820
TI  - Factors influencing physicians' decision to discharge hospitalized patients
      infected with methicillin-resistant Staphylococcus aureus.

PMID- 11571821
TI  - Dose-banding of cytotoxic drugs: a new concept in cancer chemotherapy.

PMID- 11571822
TI  - Impulse magnetic-field therapy for migraine and other headaches: a double-blind,
      placebo-controlled study.
AB  - This double-blind, placebo-controlled study assessed the efficacy of 4 weeks of
      impulse magnetic-field therapy (16 Hz, 5 microTs), delivered through a small
      device, for different types of headache and migraine. Eighty-two patients were
      randomly assigned to receive either active treatment or placebo (n = 41 each) and
      were characterized according to one of seven diagnoses (migraine, migraine
      combined with tension, tension, cluster, weather-related, posttraumatic, or
      other). Efficacy was assessed in terms of duration, severity, and frequency of
      migraine and headache attacks, as well as ability to concentrate. Data for 77
      patients were analyzed. In the active-treatment group, all assessed criteria were
      significantly improved at the end of the study (P < .0001 vs baseline and
      placebo). Seventy-six percent of active-treatment patients experienced clear or
      very clear relief of their complaints. Only 1 placebo-patient (2.5%) felt some
      relief; 8% noted slight and 2% reported significant worsening of symptoms. No
      side effects were noted.

PMID- 11571823
TI  - Three-month comparison of bimatoprost and latanoprost in patients with glaucoma
      and ocular hypertension.
AB  - A multicenter, randomized, investigator-masked, parallel-group trial compared
      bimatoprost and latanoprost for efficacy and safety in patients with glaucoma or
      ocular hypertension. Patients received bimatoprost 0.03% (n = 119) or latanoprost
      0.005% (n = 113) once daily in the evening for 3 months. Visits were at prestudy,
      baseline (day 0), week 1, and months 1, 2, and 3. Primary outcome measures were
      mean IOP and the percentage of patients achieving IOP of 17 mm Hg or lower at
      8:00 AM. Secondary outcome measures were diurnal IOP measurements (8:00 AM, 12
      noon, 4:00 PM, 8:00 PM) at month 3 and safety measures including adverse events.
      Mean IOP was lower with bimatoprost than with latanoprost at all time points
      during the 3-month follow-up, although the between-group difference was not
      always statistically significant. At month 3 at 12 noon, mean IOP was as much as
      1.0 mm Hg lower with bimatoprost (P = .021). Target pressures of < or = 17 mm Hg
      were reached more often with bimatoprost than with latanoprost at 8:00 AM (53% vs
      43%; P = .029). Over all diurnal measurements at month 3, low target pressures of
      < or = 13, < or = 14, and < or = 15 mm Hg were achieved significantly more often
      with bimatoprost (P < or = .006). Both drugs were safe and well tolerated.
      Conjunctival hyperemia was more common with bimatoprost, while headache was more
      frequent with latanoprost. Bimatoprost provided lower mean pressures than
      latanoprost at every time point throughout the study and was statistically
      superior in achieving low target pressures. More patients reached low target
      pressures with bimatoprost.

PMID- 11571824
TI  - Management of hypertension by general practitioners: an Italian observational
      study.
AB  - Data on patients receiving antihypertensive therapy were collected from 20
      general practitioners (GPs) in Campania, Italy, to determine the prescription of
      different antihypertensive classes and their use with other drugs for concomitant
      diseases, to investigate the main factors influencing antihypertensive choice, to
      document treatment outcome, and to assess adverse drug reactions (ADRs). Each GP
      completed a data card for each consultation that produced an antihypertensive
      prescription; 1900 cards were collected. The most frequently used
      antihypertensives were angiotensin-converting enzyme inhibitors (49.6%), calcium
      antagonists (24.8%), beta blockers (11.7%), angiotensin II-receptor blockers
      (5.5%), and alpha blockers (0.9%). In 82% of patients, blood pressure was reduced
      but did not reach normotensive levels. The choice of antihypertensive treatment
      was influenced by international guidelines (56%), clinical diagnosis (25%),
      concomitant diseases (8%), cost (4%), compliance (3%), and other factors (5%).
      ADRs--most often cough (35.7%), edema (22.7%), headache (13.3%), and tachycardia
      (7.8%)--occurred in 11.8% of patients.

PMID- 11571825
TI  - A new tool for predicting erectile dysfunction.
AB  - The Sexual Health Inventory for Men (SHIM) is an effective way to assess erectile
      difficulty (ED). Despite documented efficacy, however, many physicians may be
      reluctant to incorporate it into clinical practice because of the intimate nature
      of the questionnaire. In an attempt to devise and test an easy-to-use computer
      based SHIM score indicator for office use, more than 30,000 SHIM questionnaires
      were administered to men visiting physicians' offices in 2000. Information about
      age, current smoking status, diabetes, depression, hypertension, prostate
      disease, and cholesterol levels was also collected. A logistic regression model
      with a sensitivity of 81.8% and a specificity of 57.7% was created to predict the
      likelihood of ED in a patient scoring below 21 (SHIM definition). This model was
      built into a highly graphic Windows-based program. The SHIM score indicator is a
      convenient way to rapidly identify patients at high risk for ED who should be
      further assessed.

PMID- 11571826
TI  - Role of Helicobacter pylori in cirrhotic patients with dyspepsia: a 13C-urea
      breath test study.
AB  - The role of Helicobacter pylori in dyspeptic, cirrhotic patients remains unclear.
      This prospective outpatient study, conducted to assess the relationship of
      gastroduodenal disease and H. pylori as determined by the (13C) urea breath test,
      enrolled 109 consecutive cirrhotic patients with dyspepsia. All patients
      underwent upper-gastrointestinal endoscopy, which revealed respective prevalences
      of peptic ulcer, gastric ulcer, and duodenal ulcer of 41.3%, 23.9%, and 22.9%; H.
      pylori infection was found in 52.3%. The rate of peptic ulcer disease in the H.
      pylori-positive (45.6%) and -negative (36.5%) groups was not significantly
      different; neither was the prevalence of H. pylori in patients with or without
      portal hypertensive gastropathy and with or without esophageal varices. The
      relationship between peptic ulcer disease and H. pylori in dyspeptic patients
      with cirrhosis appears to be weak. Likewise, no significant relationship was
      evident between H. pylori and portal hypertensive gastropathy or esophageal
      varices. This organism may not be a major pathogenetic factor in gastroduodenal
      diseases in dyspeptic patients with cirrhosis.

PMID- 11571827
TI  - Clinical and professional reference guides. Table of critical limits.

PMID- 11571828
TI  - Clinical and professional reference guides. Table of reference intervals.

PMID- 11571829
TI  - Clinical and professional reference guides. Critical values for therapeutic drug
      levels.

PMID- 11571830
TI  - Clinical and professional reference guides. Cut-off and toxicity levels for drugs
      of-abuse testing.

PMID- 11571831
TI  - Evolution of cardio-vascular risk factors--light at the end of the tunnel?

PMID- 11571832
TI  - [Coxibs: cyclooxygenase-2 inhibitors].
AB  - The oxygenating enzyme cyclooxygenase (COX) catalysis the conversion of
      arachidonic acid to proinflammatory prostaglandins. For many years it was thought
      that COX is a single enzyme that is present constitutively in most tissues. But
      in the late 80ies COX activity was found to be increased in inflammatory states
      with cytokines and bacterial lipopolysaccharides as inducing agents. The
      expression of the induced COX is inhibited by glucocorticoids which is not the
      case with the COX known up to then. According to these findings COX exists in two
      forms, the aminoacid sequences of which are known. The expression of COX-1 is not
      or only poorly regulated, the prostaglandins produced by it are responsible for
      the protection of the gastric mucosa, maintenance of normal kidney function and
      platelet aggregation. COX-2, in contrast, is highly regulated, the prostaglandins
      produced by this isoenzyme are involved in inflammation, fever and pain but also
      in the regulation of kidney function. Conventional non-steroidal antiinflammatory
      drugs (NSAIDs) inhibit both COX-1 and COX-2. The analgesic, antipyretic and
      antiinflammatory effects of these agents are accounted for by COX-2 inhibition,
      whereas the toxic effects on the stomach as well as the inhibition of platelet
      aggregation are attributed to COX-1 inhibition. In search for selective blockers
      of COX-2, celecoxib and rofecoxib were developed which have an analgetic and
      antirheumatic potency similar to that of conventional NSAIDs but are associated
      with significantly fewer adverse gastroduodenal events. The renal toxicity of the
      selective COX-2 inhibitors is not better than that of the non-selective NSAIDs.

PMID- 11571833
TI  - Current concepts in pharmacokinetics and their implications for clinical
      medicine.
AB  - The history of medicine provides ample evidence of the physicians' struggle with
      the subject of appropriate drug dosing. Recent studies indicate that drug-related
      mortality due to inadequate dosing principles still is a leading cause of death,
      only surpassed by cardiovascular diseases, cancer and stroke. In an effort to
      rationalize drug therapy, pharmacokinetic (PK) principles were introduced in
      medical practice in the early 1970s, mainly in the field of therapeutic drug
      monitoring (TDM). This measure was shown to reduce mortality. Several limitations
      in traditional PK, however, have led to the belief among many physicians that
      clinical PK is an unnecessary assignment of limited clinical relevance. Despite
      the perceived limitations of traditional PK research, remarkable developments
      have taken place in recent years and have made clinical PK a "physiological
      mechanism based endeavor" with important implications for clinical medicine.
      Notably, the introduction of (1) PK-PD (pharmacokinetic-pharmacodynamic) modeling
      (2) target site PK (3) population PK and (4) pharmacogenomics has permitted
      better integration of PK principles into clinical drug therapy. The aim of the
      present article is to provide an overview of these developments and to discuss
      their impact on our understanding of clinical drug therapy.

PMID- 11571834
TI  - Recent trends and sociodemographic distribution of cardiovascular risk factors:
      results from two population surveys in the Austrian WHO CINDI demonstration area.
AB  - OBJECTIVE: The major risk factors for cardiovascular diseases are well
      established; however, only a few studies report on recent trends in risk factor
      profiles. This study analyses the sociodemographic distribution of risk factors
      and gives an account of their changes from 1991 to 1999. METHODS: Two cross
      sectional population surveys as part of the CINDI (Countrywide Integrated
      Noncommunicable Diseases Intervention) program of the World Health Organization
      were performed in 1991 and 1999 in the province of Vorarlberg (Austria). The
      surveys included a standardized interview and a medical examination. 1863 persons
      aged 25 to 64 years in 1991 and 1550 persons in 1999 participated in the
      interview section of the surveys. From these, 1446 in 1991 and 841 persons in
      1999 underwent medical examination. Prevalence of overweight and obesity, mild
      and severe hypertension, hypercholesterolemia, hypertriglyceridemia,
      hyperglycemia, regular smoking and lack of physical activity were estimated.
      Framingham risk functions were calculated to compare overall risk for coronary
      heart disease. RESULTS: In women, prevalence of overweight including obesity
      increased from 34% in 1991 to 41% in 1999. Almost 50% of the male population were
      estimated to be overweight or obese in 1991 and 1999. Hypertension showed a
      favorable trend and decreased substantially in both genders. Hypercholesterolemia
      decreased only in men, from 27% to 21%. In 1999, women aged 55-64 showed a
      prevalence of over 50% in highly elevated cholesterol. Hypertriglyceridemia
      decreased in men from 21% to 18%, in women it remained almost unchanged. Total
      prevalence of smoking did not change from 1991 to 1999. 34% of the men and 24% of
      the women reported to smoke more than one cigarette daily. In women under 45
      years of age, regular smoking increased slightly and reached a prevalence of over
      30%. Less educated people and people of non-national origin had significantly
      higher risk factor levels. The risk functions did not reveal a significant
      difference in 10 year risk for coronary heart disease between the two surveys.
      CONCLUSIONS: Decreasing levels in hypertension and in male hypercholesterolemia
      showed favorable developments in risk factor prevalence. Preventive measures
      should concentrate on reducing overweight in older people and smoking in young
      women as well as on intensifying the care for less educated people and people of
      non-national origin.

PMID- 11571835
TI  - Evaluation of the allergenic potential of Ginkgo biloba extracts.
AB  - Ginkgo biloba extracts are used for the treatment of central and peripheral
      malperfusion, cerebral insufficiency and dementia. Between 1996 and 1998, several
      patients in Austria who had received parenteral Ginkgo extracts were reported to
      have developed allergy-like symptoms. The aim of the present study was to
      determine whether Ginkgo biloba extracts contain type I allergens. The protein
      content of Ginkgo biloba extracts was determined by BCA protein determination and
      SDS-PAGE. We used sera from 95 polysensitized plant-allergic patients (the sera
      contained IgE antibodies against most plant allergens), and rabbit antisera
      raised against defined recombinant plant allergens. The presence of allergens in
      Ginkgo extracts was determined by dot-blotting and Wester blot. Neither rabbit
      antisera nor IgE antibodies of patients reacted to the Ginkgo extracts. In
      addition, it was shown that prick testing of the skin could be conveniently used
      to study Gingko extracts for allergenic activity. In conclusion, no evidence for
      the presence of type I allergens in Ginkgo extracts was found. We recommend
      serological and/or skin testing to exclude sensitisation to components of Ginkgo
      biloba extracts.

PMID- 11571836
TI  - Serum levels of adhesion molecules in women with pregnancy-induced hypertension.
AB  - In a matched pair study, we investigated the serum levels of intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1),
      platelet endothelial cell adhesion moleculae-1 (PECAM-1) and P-selectin in 40
      nulliparous patients with pregnancy-induced hypertension (PIH) and in 40
      normotensive pregnant controls by using an enzyme-linked immunosorbent assay
      (ELISA). Multivariate logistic regression models were used to analyze the
      influence of elevated serum levels of adhesion molecules on the occurrence of PIH
      and on the association with the severe form of the disease. The median serum
      levels of ICAM-1, VCAM-1 and PECAM-1 were significantly elevated in women with
      PIH compared to controls (296 and 222 ng/ml, p = 0.003, 633 and 505 ng/ml, p =
      0.02 and 7.7 and 6.6 ng/ml, p < 0.0001, respectively), whereas the differences of
      the median serum levels of P-selectin were not significantly between groups. In a
      multivariate logistic regression model, the serum levels of ICAM-1 and PECAM-1
      revealed a significant influence on the occurrence of PIH versus healthy pregnant
      women (p = 0.04 and p = 0.006, respectively), whereas VCAM-1 and P-selectin serum
      levels were not associated with the occurrence of pregnancy-induced hypertension
      (p = 0.3 and p = 0.2, respectively). In a multivariate logistic regression model,
      the serum levels of PECAM-1 were associated with severe disease (p = 0.002). Our
      data indicate that the expression of ICAM-1 and PECAM-1 is upregulated in
      patients with pregnancy-induced hypertension. Elevated serum levels of PECAM-1
      were associated with the development of severe disease.

PMID- 11571837
TI  - Efficacy of macrolides vs. metronidazole against Entamoeba histolytica clinical
      isolates.
AB  - Current treatment of Entamoeba histolytica infection requires the use of several
      agents that are effective at different sites of the body. Commonly administered
      agents such as nitroimidazoles have a high rate of gastrointestinal side effects
      and their use is restricted during pregnancy. In order to offer new choices, four
      macrolide antibiotics (erythromycin, clarithromycin, azithromycin, josamycin) and
      metronidazole were tested for their in vitro activity against E. histolytica. Ten
      clinically isolated strains from an endemic area (Santo Domingo, Dominican
      Republic) were tested after polyxenical culture. Protozoan viability was
      significantly reduced by josamycin after 24 and 48 hours of incubation at a
      concentration of > or = 50 mg/l, which was slightly higher than that of
      metronidazole (25 mg/l). No resistance to metronidazole was found. The antiamebic
      activity of azithromycin, clarithromycin and erythromycin was significant at drug
      concentrations > or = 100 mg/l. High doses of josamycin, which is a very well
      tolerated drug, may serve as a useful therapeutic agent in the presence of E.
      histolytica infection.

PMID- 11571838
TI  - [Intramedullary fixation of humerus shaft fractures. An analysis of complications
      of 2 implants with special reference to outcome after management with the
      unreamed humerus interlocking nail].
AB  - INTRODUCTION: Operative treatment of humeral shaft fractures has gained a new
      impetus with the development of intramedullary interlocking systems for the
      humerus. Because of the anatomical structure of the humeral marrow cavity, a
      regular jamming of nail into bone is not to be expected, so that the stability of
      these systems needs to be achieved through an interlocking mechanism. Among the
      commercially available interlocking nailing systems the unreamed humeral nail
      (UHN) and the Seidel-nail (SHN) can be regarded as the standard implants. DESIGN:
      In a retrospective study comparing two groups of patients, each treated with one
      of the two systems, problems and advantages, as well as disadvantages were
      analyzed, and the complications inherent in the systems examined. PATIENTS:
      Between 1988-1992, 47 patients with humeral shaft fractures were treated with a
      Seidel interlocking nail: 25 acute and 18 pathological fractures as well as 4 non
      unions (Group 1). Between 1997-1999, 34 patients with humeral shaft fractures
      were treated with the unreamed humeral nail (UHN). A total of thirty-five (n =
      35) nailings (30 acute and 4 pathological fractures, as well as one re
      osteosynthesis after emergence of a non-union) were carried out. Three primary
      palsies of the radial nerve ensued: two with loss of sensitivity, and one
      complete paralysis (Group 2). METHODS: Based on pre- and postoperative X-rays and
      follow-up examinations, the healing process and complications inherent in each of
      the systems were evaluated. RESULTS: Intra-operative complications of Seidel
      nailing (Group 1) were seen in 5 cases: failure of the proximal target device in
      2 (4.2%) cases; the breaking of the long screwdriver during the distal locking in
      1 (2.1%) case; blockade of nail-insertion due to the spreading distal lamellas in
      1 (2.1%) case; in 1 (2.1%) case it was impossible to find the imbus of the distal
      locking screw with the screwdriver. Incorrect surgical technique resulting in
      further fragmentation of the shaft required revisions in 2 (4.2%) cases. In 3
      cases (6.4%), the insertion of the nail was insufficient, so that an impingement
      resulted. In 12 cases, postoperative complications after Seidel-nailing resulted:
      3 (6.4%) radial nerve palsies, of which 2 (4.2%) were transitory; 3 (6.4%)
      infections; in 3 (6.4%) cases, loosening of the locking bolt inserted in the
      frontal plane; in 1 (2.1%) case, loosening of the distal spreading screw. The
      system failed in treating 2 (of 4) non-unions, whereas successful ossification
      and repair occurred in all acute fractures. In Group 2 (UHN) the acute fractures
      of 33 cases healed without complications. Intra-operative complications of the
      unreamed nail: in 2 cases (5.6%), failure of the target devices resulted in
      malpositoning of interlocking screws. The following intra-operative complications
      of the retrograde technique were observed: burst of a fragment at the insertion
      site in 1 case (2.8%); intra-articular positioning of the most proximal
      interlocking screw in another case (2.8%). Postoperative complications of the
      unreamed nail: breaking of a proximal and a distal interlocking screw in 1 case
      (2.8%), which had no influence on the healing progress. In 1 case (2.8%) both
      proximal interlocking screws came loose and a non-union ensued. After re
      osteosynthesis with the same technique, bony repair was achieved. CONCLUSION: The
      possibilities of operative methods in treatment of humeral shaft fractures are
      enhanced by intramedullary interlocking systems. Comparing with the Seidel nail,
      the unreamed humeral nail (UHN) has two advantages: it can be inserted
      anterogradely as well as retrogradely, and it provides the possibility of
      compressing the fracture, resulting in a high rotational stability. Due to these
      results, the application of the UHN is recommended.

PMID- 11571839
TI  - [Therapy of neurotrophic keratopathy in trigeminal schwannoma with radiosurgery].
AB  - BACKGROUND: We present a patient with neurotrophic keratopathy due to a
      trigeminal nerve neurinoma, who was successfully treated by radiosurgery.
      PATIENT: A patient was referred to us with recurrent corneal erosions of unknown
      origin in his left eye. In addition, he suffered from mild hypoesthesia in the
      distribution of the first branch of the trigeminal nerve. He was started on
      topical lubricants (hyaluronic acid 0.5%) and antibiotic ointments (gentamycin),
      but since no corneal healing occurred, a soft contact lens was applied. The
      patient developed severe corneal neovascularization within four weeks and the
      contact lens had to be removed. Three months later an MRI scan was performed,
      which showed an intracranial tumor originating from the first branch of the
      trigeminal nerve. Neurinoma of the trigeminal nerve was suspected, and this
      presumed diagnosis was confirmed by fine needle biopsy. The patient underwent
      radiosurgery seven weeks later. The epithelium closed, the cornea recovered and
      stayed stable until the last examination 18 months after radiosurgery.
      CONCLUSION: Radiosurgery is a promising alternative to conventional microsurgery
      in cases of neurinomas of the trigeminal nerve including neurotrophic
      keratopathy, to keep or restore vision.

PMID- 11571840
TI  - "Wiener klinische Wochenschrift": publication patterns 1990-2000.
AB  - The impact factor (Institute for Scientific Information, ISI, Philadelphia, PA,
      USA) is a widespread used and acknowledged source for judging the quality of a
      researcher. In addition the "Science Citation Index (SCI)" [Institute for
      Scientific Information (ISI)] provides the scientific community with a citations
      database indicating the number of cited references in indexed articles. For
      several reasons, the SCI seems to be more relevant. To evaluate the quality of
      the journal "Wiener klinische Wochenschrift", we assessed how often contributors
      to this journal have been cited during the last decade and which contributions
      have ranked as top papers. Moreover, with the aim of a more objective type of
      scientific evaluation, we have employed a new score, the "Citation Per Time Score
      (CPT-Score--the SCI divided by the number of years of observation, starting one
      year after publication). We have evaluated the total SCI for the years 1990 to
      1994 and for the years 1995 to 1999. The number of total citations between the
      appearance of an article and the year 2000 was analyzed. The highest ranked
      publication of the whole decade (1990-2000) was a paper by G. Stanek with 40
      citations. Furthermore, we have evaluated the "Top Ten Papers" of the journal.
      Interestingly, a steady increase of the total citation index of the journal
      "Wiener klinische Wochenschrift" over the last decade could be demonstrated. This
      study clearly shows that the citation rate of an article is not determined by the
      impact factor of the journal but rather the quality of the contribution.
      Moreover, the citation analysis of papers published in the last ten years in the
      "Wiener klinische Wochenschrift" shows a satisfactory citation rate for articles
      published in this journal. It is therefore definitely attractive to submit an
      article to a journal such as the "Wiener klinische Wochenschrift".

PMID- 11571841
TI  - [Communication barriers in the management of immigrants and their children. An
      analysis and possible solutions based on case reports].
AB  - Up to 41% of patients treated in health care institutions and hospitals in Vienna
      are non-German-speaking. As one half of the foreign population of Vienna speaks
      little or no German, their treatment in health care institutions is a difficult
      issue. Based on exemplary case reports, linguistic and socio-cultural
      communication barriers in health care are presented and the problematic area of
      foreign-language communication is analysed. Misunderstandings due to
      communication barriers not only have a negative financial impact on health care
      economy, they also complicate the individual care of these patients. Based on the
      experience gained thus far and in concurrence with the developments in other
      European countries, the use of professional interpreters who combine their role
      as linguistic intermediaries with the cultural features of foreign-language
      patients (community interpreters) should be encouraged. The use of specifically
      trained internal hospital staff is recommended as well. A concept to coordinate
      central organisations that provide interpreters in the public field may
      substantially enhance the quality and efficiency of health care in this special
      situation.

PMID- 11571842
TI  - [Ethical aspects of euthanasia].

PMID- 11571843
TI  - Why are infants prone to wheeze? Physiological aspects of wheezing disorders in
      infants.
AB  - Wheezing in infants is common and increasing in prevalence. Infants are
      particularly prone to wheezing due to developmental differences in airway
      mechanics compared to adults. These effects are enhanced in the presence of
      airway inflammation. Wheezing in infants is related to flow limitation which is a
      function of airway calibre and airway wall compliance. This review discusses the
      factors contributing to flow limitation and hence, wheezing. It tries to make the
      link between risk factors influencing airway structure, and thus function, with
      particular emphasis on the special physiological peculiarities of infants and
      lung growth. While in adults inflammation and remodelling alone may explain
      structural and functional changes in wheezing disorders, this reviews proposes a
      model emphasising that in infants inflammation, remodelling and airway
      development have to be considered as a continuously interacting system.

PMID- 11571844
TI  - Pulmonary rehabilitation in outpatients with asthma or chronic obstructive lung
      disease. A pilot study of a "modular" rehabilitation programme.
AB  - STUDY/PRINCIPLES: Pulmonary rehabilitation programmes are often costly and
      dependent on the infrastructure of specialised centres. We developed a modular,
      outpatient-based rehabilitation programme, which is inexpensive and can be
      implemented in a variety of settings. The aim of this study was to determine the
      effects and feasibility of this programme. METHODS: Thirteen patients with COPD
      and 7 patients with asthma were enrolled by their primary care physician because
      of dyspnoea. Initial assessment included cardiopulmonary exercise testing, six
      minute walking distance, lung function testing and multiple questionnaires
      addressing dyspnoea, depression and quality of life issues. The training
      consisted of 36 sessions of high intensity training of 2 hours duration to
      improve exercise tolerance, including 30 minutes of stationary cycling at the
      anaerobic threshold. Another complete assessment was done on completion of the
      study at 3 months. RESULTS: The six-minute walking distance improved
      significantly from 401 to 551 m (p < 0.0001). The maximal exercise capacity
      increased significantly from 85 W to 99 W (p < 0.001). The anaerobic threshold
      remained unchanged despite the high intensity training. There was a reduction of
      dyspnoea and an improvement of quality of life. CONCLUSION: This study shows that
      our outpatient rehabilitation programme leads to a benefit in exercise tolerance
      and health related quality of life comparable to other programmes published in
      the literature. The rehabilitation programme was very well accepted among
      patients, primary care physicians and health insurers.

PMID- 11571845
TI  - Renal pathology and premortem clinical presentation of Caucasian patients with
      AIDS: an autopsy study from the era prior to antiretroviral therapy.
AB  - PRINCIPLES: Renal disease in patients with HIV infection is becoming increasingly
      frequent. A particular form of HIV-associated nephropathy (HIVAN) has been found
      in patients of predominantly African-American and Hispanic origin. However, only
      limited data are available on renal pathology and premortem clinical presentation
      of kidney disease in Caucasian patients with AIDS. METHODS: To determine the
      prevalence, clinical presentation and aetiology of renal disease in Caucasian
      patients with AIDS at the time of death we have performed a prospective autopsy
      study with 239 patients who died of AIDS between 1981 and 1989. None of these
      patients had received HIV-specific antiretroviral therapy. Autopsies and
      histological analyses were performed on the basis of a standardised protocol.
      Clinical and laboratory data were gathered according to a uniform questionnaire.
      RESULTS: 95% of patients were of Caucasian race. 75% of all patients had extended
      AIDS (stage IV). Clinical signs of nephropathy prior to death were found in 36%
      of patients, including proteinuria (18%), abnormal urinary sediment (19.5%), and
      renal insufficiency (11%). Histopathological lesions were present in 43% of the
      autopsies, with two or more distinct structural lesions in 12.5% of patients. Of
      the pathological findings 28% were glomerular or vascular, 33% were non
      glomerular, and 29% were combined lesions. The remaining 10% were renal
      infiltrations of infectious agents or neoplastic tissue. The most common findings
      were ischaemic changes and vascular scars (18% of patients), as well as pyelo-
      and interstitial nephritides (12.2%). Importantly, FSGS was present in only 1.7%
      of patients, and only a single African patient had classical HIVAN. CONCLUSIONS:
      Renal involvement in HIV disease is very common at the time of death among
      patients of Caucasian origin. However, classical HIV-associated nephropathy is
      absent in this population. These findings suggest that kidney disease affects all
      races and supports the hypothesis that HIVAN is specifically related to non
      Caucasian ethnicity. The results reflect renal disease unaffected by HIV-specific
      antiretroviral therapy.

PMID- 11571846
TI  - Epidemiological and economical impact of tuberculosis in an adolescent girl in
      Lausanne (Switzerland).
AB  - Patients with pulmonary tuberculosis (TB) can infect people in their environment
      but children and adolescents are rarely contagious. A recent case of an
      adolescent girl in Lausanne, however, proved to be infectious and required
      extensive contact tracing. SUBJECTS AND METHODOLOGY: The source case was a 15
      years-old adolescent girl of African origin. Upon her arrival in Switzerland in
      1994 the tuberculin skin test was 14 mm. The patient did not receive preventive
      treatment. She developed smear-positive pulmonary tuberculosis in May 1999.
      Contact tracing identified contacts in the surrounding population. The contact
      persons were divided into 3 groups according to their proximity. The first group
      consisted of close family and friends, the second of classmates and teachers and
      the third of more distant contacts. Costs were also evaluated. RESULTS: Of the 53
      people examined, 24 (45%) were infected and required treatment. Eight out of 9
      cases (88%) were infected in the first group (including another case of culture
      positive pulmonary tuberculosis). Fourteen out of 33 cases (42%) in the second
      group and 2 of 11 (18%) to the third group. Passing from one proximity group to
      the next decreased the relative risk of infection 4 fold. The costs of contact
      tracing and treatment are estimated at over CHF 24,000. CONCLUSIONS: (1)
      Pulmonary TB can be contagious even in adolescents. (2) Subdividing contacts into
      proximity groups allows for better targeting of the people to be screened. (3)
      Contact tracing and the high costs involved could have been avoided if the
      patient had received preventive chemotherapy upon her arrival in Switzerland.

PMID- 11571847
TI  - A reduction in HIV positive and an increase in hepatitis C positive subjects in
      methadone maintenance treatments.

PMID- 11571848
TI  - [Arteriosclerosis--an ultrachronic Chlamydia infection].

PMID- 11571849
TI  - [Paths to infarction; new findings through in-vivo-rheoscopy].

PMID- 11571850
TI  - [ACE inhibition and atherogenesis].

PMID- 11571851
TI  - [Cholesterin synthase inhibition and atherosclerosis].

PMID- 11571852
TI  - [Diagnostic value of cardiologic stress tests].

PMID- 11571853
TI  - [Intracranial progressive epitheloid-cell granulomas during anti-tubercular drug
      therapy].

PMID- 11571854
TI  - [52-year old patient with skin discoloration].

PMID- 11571855
TI  - [Therapy of functional dyspepsia (irritable stomach syndrome].

PMID- 11571856
TI  - [Danish biomedical research in the post-genomic era].

PMID- 11571857
TI  - [Genetic screening of bipolar affective disorder].

PMID- 11571858
TI  - [Gene expression analysis of myelomatosis].

PMID- 11571859
TI  - [The Human Genome Project--status and perspectives].

PMID- 11571860
TI  - [Coronary atherosclerosis assessed by coronary angiography or intravascular
      ultrasound].
AB  - Intensive lowering of serum cholesterol in patients with ischaemic heart disease
      may retard atherosclerotic progression, and may even cause a limited regression
      in some patients and partly restore endothelial function. Coronary angiography
      has been the standard method to evaluate coronary anatomy. However, coronary
      angiography delineates only the vessel lumen as a silhouette, a perspective that
      is incapable of reflecting the irregular nature of the atherosclerotic vessel
      wall changes. Three-dimensional intravascular ultrasound provides cross-sectional
      and longitudinal images of both the vessel lumen and wall and the plaque volume
      can be measured in entire arterial segments. Three-dimensional intravascular
      ultrasound is a reliable technique to measure progression and regression of
      atherosclerosis in coronary arteries.

PMID- 11571861
TI  - [The molecular genetic background of hereditary craniosynostoses and
      chondrodysplasias].
AB  - Fibroblast growth factors are structurally related proteins associated with cell
      growth, differentiation, migration, wound healing, angiogenesis, and oncogenesis.
      At the cellular level, their function is mediated by transmembrane tyrosinekinase
      receptors, fibroblast growth factor receptors. Four genes encoding fibroblast
      growth factor receptors have been identified, and mutations in three of these,
      FGFR1, FGFR2, and FGFR3, can cause different congenital, autosomal dominant
      disorders affecting the craniofacial and skeletal development: craniosynostosis
      and chondrodysplasias. The craniosynostosis syndromes: Apert syndrome, Beare
      Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Muenke syndrome,
      Pfeiffer syndrome and Saethre-Chotzen syndrome can be caused by mutation in
      either FGFR1, FGFR2, or FGFR3. Saethre-Chotzen syndrome can also be caused by
      mutation in a functionally related gene, ACS. The same mutation can cause
      different syndromes, and the same syndrome can be caused by mutations in
      different genes. The chondrodysplasias: achondroplasia, hypochondroplasia, and
      thanatophoric dysplasia are all caused by mutations in FGFR3.

PMID- 11571862
TI  - [Antibiotic resistance of E coli isolated from healthy persons].
AB  - INTRODUCTION: The aim of the study was to determine the antibiotic susceptibility
      of E. coli isolates in stools from healthy Danes. METHODS: Sixty-nine persons
      from Copenhagen participated in the study. Three faecal samples from each
      participant were examined by culture for each of three periods. E. coli was
      isolated selectively and tested for sensitivity against sulfamethizole,
      trimethoprim, the combination of sulfamethizole and trimethoprim, ampicillin,
      mecillinam, cefuroxime, nitrofurantoin, and ciprofloxacin. RESULTS: Altogether,
      184 strains of E. coli were isolated from 66 of the 69 persons. Fifty-eight
      (31.5%) of the strains isolated from 30 persons (43.5%) were resistant to
      sulfamethizole, 32 (17.4%) strains isolated from 18 persons (26.1%) were
      resistant to trimethoprim, 31 (16.8%) strains isolated from 17 persons (24.6%)
      were resistant to trimethoprim + sulfamethizole, 57 (31%) strains from 31 persons
      (44.9%) were resistant to ampicillin, 29 (15.8%) of the strains from 24 persons
      (34.8%) were resistant to nitrofurantoin, two (1.1%) strains from two persons
      (2.9%) were resistant to cefuroxime, whereas none of the strains was resistant to
      mecillinam and ciprofloxacin. DISCUSSION: The high prevalence of resistance to
      sulfamethizole, ampicillin, trimethoprim, and nitrofurantoin is surprising, as
      none of the persons had been treated with antibiotics, but it may reflect the
      widespread use of antibiotics in animals for food production. The consequences of
      the results for empiric antibiotic treatment of, for instance, urinary tract
      infection are discussed.

PMID- 11571863
TI  - [Documentation problems in anesthesiology and gynecology?].
AB  - INTRODUCTION: The number of beds in surgical wards is declining. Whether the
      reason is more outpatient surgery or quicker recovery, owing to better
      perioperative care is unknown. MATERIALS AND METHODS: A questionnaire was sent to
      all gynaecological and anaesthetic departments in Denmark concerning the
      treatment of women who had had a hysterectomy for non-malignant disease. The
      following questions were asked: What were the numbers of patients operated on in
      1998, the methods of operation, duration of admission, the surgeon in charge,
      information about admission and postoperative management of patients, choice of
      anaesthesia and treatment of postoperative pain. RESULTS: The chief surgical
      method was abdominal hysterectomy. There were relatively few vaginal or
      laparoscopically assisted hysterectomies. The duration of admission varied
      considerably. Patients mostly were given written information about admission and
      the postoperative course. Postoperative follow-up was relatively uncommon. The
      duration of admission was not influenced by the anaesthetic method. Seventeen of
      31 anaesthetic departments knew the number of patients anaesthetised for
      hysterectomy in 1998 and the anaesthetic methods. DISCUSSION: This study cannot
      answer the question: How does the method of operation, choice of anaesthesia,
      postoperative analgesia, and information to the patient affect the duration of
      admission? Data allowing a discussion of the quality of the treatment were not
      available. There is a serious lack of registration.

PMID- 11571864
TI  - [Cohort study of fracture risk before and after surgery of primary
      hyperparathyroidism].
AB  - We studied the risk of fracture in 674 patients operated on for primary
      hyperparathyroidism compared to 2,021 age- and gender-matched controls, matched
      for age and gender, randomly drawn from the background population. Before
      surgery, there was an increased risk of fracture (relative risk 1.8, 9%
      confidence interval 1.3-2.3), but after surgery the relative risk was normalised
      (RR = 1.0, 0.8-1.3). The increased risk began ten years before surgery and peaked
      five to six years before surgery. After surgery, there was a temporary increase
      in the first year, but in the following years the fracture risk was normalised,
      with a small rise in distal forearm fractures more than ten years after surgery.
      Primary hyperparathyroidism may have started up to ten years before surgery, and
      the fracture risk is normalised after surgery.

PMID- 11571865
TI  - [Ruptured popliteal aneurysm].
AB  - A 56-year-old man with Down's syndrome and a known popliteal aneurysm 6 cm in
      diameter was seen with a huge distal femoral mass which had been present for
      about two months. At operation, the original thrombus from a ruptured aneurysm
      was enucleated, the aneurysm excluded, and a femoropopliteal in situ bypass
      performed. At twelve months follow-up, the patient presented with a foot pulse
      and an unchanged peroneal nerve deficit.

PMID- 11571866
TI  - [Low-dose hydrocortisone treatment of catecholamine refractory septic shock].
AB  - Treatment with corticosteroids in patients with septic shock is controversial.
      Dosage and timing of treatment differ in clinical trials. The effect of LDHT (low
      dose hydrocortisone therapy) is based on the hypothesis of a relative
      adrenocortical insufficiency. Two cases in which septic shock was reversed with
      LDHB are described.

PMID- 11571867
TI  - [A survey of medical end-of-life decisions in six different European countries].

PMID- 11571868
TI  - [Crying for hours--but what is the cause?].

PMID- 11571869
TI  - [Can sclerosis be inhibited by vitamin D?].

PMID- 11571870
TI  - [Research in general practice--necessary and possible].

PMID- 11571871
TI  - [Water and health in an international perspective].

PMID- 11571872
TI  - [Cognitive problems after coronary surgery].

PMID- 11571873
TI  - [Treatment of multiple sclerosis].

PMID- 11571874
TI  - [Waiting lists, loss of health and hospital capacity].

PMID- 11571875
TI  - [Health status of patients on waiting lists].
AB  - BACKGROUND: The waiting lists for hospital admission are used as arguments for
      more resources to hospitals. Concern is expressed that the attention given to
      waiting list patients has the effect that less resources are devoted to other
      groups of patients. This article reports on a study of whether waiting list
      patients are in poorer health that persons who are not on a waiting list.
      MATERIAL AND METHODS: A random sample of 5,000 Norwegian citizens were drawn to
      be included in Statistics Norway's 1998 quality and standard of life survey.
      Interviews were obtained with 3,449 persons. Binomial and multinomial logistic
      analyses were used. RESULTS: Individuals in poor health have a higher probability
      of being on a hospital waiting list than have persons in good health. We did not
      find any relationship between state of health and a patient's experienced waiting
      time. INTERPRETATION: Our findings reject the assertion of arbitrariness
      regarding the selection of patients to hospital waiting lists. The lack of effect
      of state of health on experienced waiting time could be interpreted in several
      ways.

PMID- 11571876
TI  - [Drug treatment of school children with attention deficit and hyperactivity
      disorder].
AB  - BACKGROUND: The use of stimulants in the treatment of AD/HD has increased
      dramatically over the last twenty years. We wanted to assess the prevalence of
      students treated with stimulants in the elementary schools in the city of
      Trondheim, Norway. MATERIAL AND METHODS: Fifty of 53 schools (94%), representing
      16,141 students, answered two questionnaires. Mentally retarded, autistic and
      otherwise severely handicapped students attending special groups or schools, were
      excluded. RESULTS: In all, 57 students (3.5 per 1,000) were treated with either
      methylphenidate or racemic amphetamine. Multivariate analysis suggested that the
      structure of the classroom was an essential risk factor for being treated with
      stimulants. The risk was higher in so-called "open schools" (no fixed walls
      between groups of students) than in schools with traditional classrooms (< 30
      students in rooms separated by fixed walls). (Odds ratio: 5.5; 95% confidence
      interval: 1.1-26.4.) More detailed information was obtained from 47 of the 57
      students; only one of whom was female. Teaching resources required for optimal
      pedagogical treatment were available for about one out of two of these 47
      students. INTERPRETATION: Our results do not suggest that an inappropriately high
      proportion of students in the region are taking stimulants for AD/HD. On the
      contrary, AD/HD may be underdiagnosed and inadequately treated in girls. It seems
      likely that students with AD/HD are less likely to be treated with stimulants in
      schools with traditional classrooms, and our results also suggest a lack of
      teaching resources for these students.

PMID- 11571877
TI  - [Risperidone as a tool to control hard aggression].
AB  - BACKGROUND: It is a challenge to give adequate help to patients who have problems
      controlling their aggression. Stimulation of 5-HT1A receptors and blockage of 5
      HT2A receptors is known to have antiaggressive effects. Risperidone is an
      antipsychotic drug with a combined effect as a dopamine antagonist and a 5-HT2A
      receptor antagonist. MATERIAL AND METHODS: Risperidone in dosages from 0.25 to 1
      mg daily was administered to 11 patients with restlessness, concentration
      problems, tics and aggression that was hard to control. The patients were 11 to
      47 years of age, most of them were also taking other medications, and all
      received other kinds of treatment, e.g. psychotherapy. There was no control
      group. RESULTS: More than half of the patients gained far better control of their
      temper. Two of the patients were taken off risperidone treatment after a short
      period of time because of side effects and no effect on temper. INTERPRETATION:
      The observed effect of risperidone on aggression is in concordance with other
      reports, but in lower dosages than reported elsewhere. Risperidone therefore
      seems promising as an adjuvant in treating patients with hard controllable
      aggression, even in very low dosages, though their is a need for systematic
      studies to assess the effect.

PMID- 11571878
TI  - [Polymyalgia rheumatica in general practice].
AB  - BACKGROUND: Polymyalgia rheumatica is often diagnosed and treated in general
      practice. Rheumatologists have expressed concern about overdiagnosing and steroid
      treatment that conceals other diseases and deteriorating osteoporosis. MATERIAL
      AND METHODS: A ten-year material (1985-94) of polymyalgia rheumatica from a
      Norwegian general practice. RESULTS: Six out of 54 patients with the diagnosis
      polymyalgia rheumatica had their diagnose changed after one year. Average
      prednisolone starting dose was 31 mg, median treatment time for women was 20
      months and for men 29 months. 10% were treated more than ten years, and 20%
      relapsed. Patients with fractures in the follow-up period had longer treatment
      periods; this indicates that a shorter treatment time may be important in
      preventing osteoporosis. INTERPRETATION: Diagnosing polymyalgia rheumatica can be
      done in general practice if there is good communication with second-line medical
      services in cases with indistinct or serious symptoms. It is important to have in
      mind temporal arteritis, rheumatoid arthritis and malignancies. Treatment and
      follow-up of these patients is a task that needs stable and continuous relations
      between patient and doctor with special focus on the osteoporosis problem.

PMID- 11571879
TI  - [Preoperative parathyroid scintigraphy in primary hyperparathyroidism].
AB  - BACKGROUND: The primary benefit of preoperative scintigraphy in patients with
      primary hyperparathyroidism not previously surgically explored seems to be the
      possibility of unilateral or limited access surgery in selected patients.
      MATERIAL AND METHODS: We studied the accuracy of scintigraphy using 99mTc
      sestamibi and dual phase imaging protocol combined with thyroid scintigraphy
      using 99mTc pertechnetate before conventional neck exploration and histologic
      verification in 78 consecutive patients. RESULTS: In 65 patients with solitary,
      focal uptake on scintigraphy, we found a solitary adenoma in 61 patients (94%), a
      solitary adenoma on the contralateral side in one patient, two adenomas on the
      indicated side in one patient, bilateral adenomas in one and hyperplasia in one
      patient. In 13 patients with a negative or equivocal scintigraphic result, eight
      had a solitary adenoma and five hyperplasia. INTERPRETATION: These result may
      support a limited unilateral surgical approach when scintigraphy shows a
      localized focal uptake and this is confirmed perioperatively. In experienced
      hands the risk of overlooking an adenoma will be small. However, it is mandatory
      to have an experienced parathyroid surgeon prepared to proceed with full neck
      exploration when this is necessary.

PMID- 11571880
TI  - [Acute respiratory failure caused by myotonic dystrophy].
AB  - BACKGROUND: Respiratory insufficiency is not always caused by pulmonary diseases
      or diseases involving the pulmonary vasculature. MATERIAL AND METHOD: We present
      a case history of a 29-year-old patient with acute respiratory insufficiency
      following a gynaecological operation. RESULTS: Ventilation/perfusion scintigraphy
      and spiral-CT of thorax excluded pulmonary embolism. Chest X-ray demonstrated
      elevated diaphragm and slight right-sided atelectatic changes. Spirometry
      revealed a restrictive ventilatory capacity, which explained the patient's
      hypoxaemia. Phrenic nerve conduction studies were normal on both sides.
      Electromyography showed severe myotonic discharges in all examined muscles
      including intercostal musculature and the diaphragm. INTERPRETATION: Myotonic
      dystrophy was the cause of respiratory failure in this patient. The case
      demonstrates that respiratory failure may be caused by neuromuscular diseases,
      hence the importance of adequate neurophysiological investigation in such
      patients.

PMID- 11571881
TI  - [Skin neoplasms in general practice].
AB  - BACKGROUND AND OBJECTIVE: General practitioners diagnose and treat benign and
      malignant skin tumours. We have performed a retrospective study of all skin
      neoplasms diagnosed in a general practice. MATERIAL AND METHODS: Information on
      all skin neoplasms presented in one general practice in 1990-1999 were obtained
      by retrospective search of notes from 41,601 consultations (electronic files) and
      a handsearch of the paper-based archives. RESULTS: A total of 568 skin tumours
      had been diagnosed, i.e. 1.37 tumours per 100 consultations. 60% of the patients
      were women, median age was 49 years. Nevi, seborrheic keratoses and
      dermatofibromas were the most frequent diagnoses. 26 malignant skin lesions had
      been diagnosed, among them 19 basal cell carcinomas and three malignant
      melanomas. All skin cancers were taken care of at the first consultation, by
      excision, referral, or an early new appointment for further evaluation.
      INTERPRETATION: Skin tumours are frequently diagnosed and treated in general
      practice.

PMID- 11571882
TI  - [Placebo effect in research related to surgery and technical procedures].
AB  - BACKGROUND: Development of new technology has led to the introduction of many new
      high-tech surgical treatment modalities. It has been claimed that the use of high
      tech medicine is a potent inductor of placebo effect; in fact, many new treatment
      modalities have been established before they have been evaluated in placebo
      controlled trials. However, there are several ways to minimize the confounding
      effects of placebo in surgical trials. MATERIAL AND METHODS: This is a review
      based on a thoroughly performed search on Medline of Norwegian and English
      language publications published up until August 2000. RESULTS: Several studies
      have demonstrated that surgical treatment induces significant placebo effect. To
      minimize the confounding effects of placebo in trials evaluating new surgical
      modalities, it is important to use adequate blinding, neutral patient
      information, objective end-points, and correction for estimated placebo effects.
      The use of placebo surgery has been a source of lively controversy; many consider
      it ethically unacceptable.

PMID- 11571883
TI  - [Why are patients referred to outpatient clinic of rheumatology?].
AB  - BACKGROUND: Increasing numbers of patients are referred from general
      practitioners to out-patient clinics of rheumatology. Better selection of
      patients referred may shorten the long waiting lists. The study aimed at
      analysing causes of referrals with particular emphasis on determining which
      diagnostic problems that most often occur among such referrals. MATERIALS AND
      METHODS: All referrals from general practitioners to an out-patient clinic of
      rheumatology during one year were analysed. RESULTS: Diagnosis was the main cause
      of referral in 78% of the cases. The diagnosis of the specialist was identical to
      that of the general practitioner in 44% of the cases. The lowest degree of
      correlation was found for patients referred with rheumatoid arthritis and primary
      Sjogren's syndrome. INTERPRETATION: The diagnoses of rheumatoid arthritis and
      Sjogren's syndrome appear to be difficult in general practice.

PMID- 11571884
TI  - [Dosing of drugs to the elderly].

PMID- 11571885
TI  - [A national model for drug-supported rehabilitation of opiate addicts].

PMID- 11571886
TI  - [Public misunderstanding within health services concerning research].

PMID- 11571887
TI  - [Should treatment of extremely premature infants be centralized?].

PMID- 11571888
TI  - ["Now we have washed the floor..."].

PMID- 11571889
TI  - [Public sector's responsibility to provide physicians with drug information].

PMID- 11571890
TI  - [The psychiatric reform, distribution of physicians and equal accessibility].

PMID- 11571891
TI  - Glucksberg, the putative right to adequate pain relief, and death with dignity.
AB  - This Article focuses on the legality of the aggressive use of analgesics and deep
      sedation for terminally ill patients. The author analyzes the 1997 Supreme Court
      decisions on physician-assisted suicide, examines the tension between
      controversial palliative care practices and the traditional legal framework, and
      explores the contours of an emerging constitutional right to avoid suffering at
      the end of life. In addition, the author argues that deep sedation together with
      withholding of artificial nutrition and hydration should be an option for dying
      patients suffering from severe physical or emotional pain.

PMID- 11571892
TI  - The collision of healthcare and corporate law in a hospital closure case.
AB  - This Article analyzes potential conflicts that arise from both the judicial and
      administrative approval processes that govern the closure of charitable hospitals
      through a sale of all or substantially all of their assets. Examining the recent
      closure attempt by the Manhattan Eye, Ear & Throat Hospital as an example, the
      Article highlights the various public health and corporate law issues that are
      raised when a not-for-profit hospital seeks closure. The Article thoroughly
      discusses both the statutorily and judicially required approval schemes
      applicable to the closure of charitable hospitals. The Article also suggests ways
      in which these conflicts might be avoided or remedied, as well as gives advice
      regarding hospital board decisionmaking.

PMID- 11571893
TI  - Legal considerations of sleep deprivation among resident physicians.
AB  - Medical training in the United States often takes the form of a grueling
      endurance test in which patients are often those most at risk. This Article
      discusses sleep deprivation among resident physicians in the United States with
      an eye towards resolving the problem through legal channels. It analyzes the
      effects of sleep deprivation on resident physicians, with subsequent discussion
      of the implications for patient care and medical training. Next, it makes
      comparisons to medical training in other developed nations, as well as
      regulations that exist in the airline and trucking industries, where public
      safety is a principal concern. Furthermore, this Article discusses proposals to
      mend the dilemmas created by sleep-deprived resident physicians through statutory
      and regulatory reform, deterrence by way of tort law, and unionization or
      collective bargaining.

PMID- 11571894
TI  - Rethinking blood shield statutes in view of the hepatitis C pandemic and other
      emerging threats to the blood supply.
AB  - Researchers have identified at least twenty-five pathogens that can be
      transmitted through blood transfusions. Four percent of patients who receive the
      average amount of blood during a transfusion are at risk of being infected with a
      contaminated unit, and exposed to the danger of serious adverse reactions,
      including future debilitating conditions. Victims of transfusion-related
      diseases, however, generally have been unsuccessful when making claims against
      the purveyors of blood products because of blood shield statutes that were
      initially enacted in response to unknown pathogens that made the blood an
      "unavoidably unsafe" product. Today, blood purveyors are aware of the possibility
      of epidemics from unsafe blood and have continued to research and supervise the
      blood supply to create mechanisms that detect and inactivate various blood-borne
      pathogens. In response to the current and advancing methods of blood
      purification, this Article suggests that a hybrid strict liability/negligence
      standard be implemented to ensure advancements in safety of blood transfusions. A
      strict liability standard should attach for infections that can be detected and
      eliminated through current testing and inactivation methods. A negligence
      standard should govern infections for which no current test or inactivating
      method is available. Under this approach, blood purveyors would be compelled to
      take account of the risks of any manufacturing decisions that they make, and they
      would not enjoy the freedom from liability that the blood shield statutes now
      provide. The costs necessary to ensure compliance with this hybrid structure are
      small in comparison to the social and economic costs exacted by thousands of
      transfusion-related diseases.

PMID- 11571895
TI  - Pain and disability under Social Security: time for a new standard.
AB  - Some degree of pain is a part of every individual's life. Many people, however,
      live in chronic debilitating pain. This Article examines concepts of pain and its
      treatment and implications for victims of pain under the Social Security system.
      The Article discusses inconsistencies within the Social Security Administration
      and in the courts when attempting to set standards for evaluating pain and
      determining disability.

PMID- 11571896
TI  - Section 525(a) of the bankruptcy code plainly does not apply to Medicare provider
      agreements.
AB  - Section 525(a) of the Bankruptcy Code prevents government entities from
      discriminating against debtors based on the debtor's bankruptcy filing. This
      Article analyzes how this provision is applied to healthcare providers who file
      for bankruptcy. Some commentators have expressed concerns that because of Section
      525, the federal government is unable to deny a bankrupt provider a new Medicare
      provider agreement due to the debtor's failure to pay debts discharged during
      bankruptcy. This Article, however, argues that Section 525 does not apply to a
      provider agreements because it is not a "license, permit, charter, franchise, or
      other similar grant" as defined by the statute. Therefore, the author concludes
      that debtor healthcare providers should not be allowed back into the Medicare
      program without first paying their statutorily required debts.

PMID- 11571898
TI  - Creating knowledge management skills in primary care residents: a description of
      a new pathway to evidence-based practice.

PMID- 11571897
TI  - Sample patient medical information use and disclosure notice.
AB  - In accordance with the federal health privacy standards promulgated pursuant to
      the Health Insurance Portability and Accountability Act of 1996 ("HIPAA"),
      covered entities must provide adequate notice to individuals of their policies
      and procedures regarding protected health information. The form below may be used
      as a starting point by covered entities for the development of such notice.

PMID- 11571899
TI  - Review: anticoagulants may be better than antiplatelet agents for nonfatal stroke
      but not other vascular or fatal events in nonrheumatic AF.

PMID- 11571900
TI  - Preoperative assessment for pulmonary resection.
AB  - Because of recent advances in anesthesia and surgery, almost any patient with a
      resectable lung malignancy is now an operative candidate, given a full
      understanding of the risks and provided he or she is investigated appropriately.
      This progress necessitates a change in the paradigm that one uses for
      preoperative assessment. Understanding and stratifying the perioperative risks
      allows the anesthesiologist to develop a systematic focused approach to these
      patients at the time of the initial contact and immediately before induction,
      which then can be used to guide anesthetic management (Fig. 7).

PMID- 11571901
TI  - Pathophysiology of one-lung ventilation.
AB  - The management of some problematic patients having thoracic surgery is among the
      most difficult challenges for the anesthesiologist. Increasingly complex
      operations are performed on seriously compromised patients because of the
      development of new surgical techniques and the anesthesiologists' awareness of
      surgical needs and requirements to provide a satisfactory and safe surgical
      field. In order to facilitate thoracic surgery, the single most important and
      valuable anesthetic technique used actually is one-lung ventilation. This article
      reviews the complex pathopysiology of one-lung ventilation.

PMID- 11571902
TI  - Lung isolation techniques.
AB  - Left-sided double-lumen endotracheal tubes should be the tube of choice for most
      cases in which lung isolation is required. A right-sided double-lumen
      endotracheal tube can be used effectively when a contraindication to placing a
      left-sided double-lumen endotracheal tube exists. The method of choice to select
      left-sided double-lumen endotracheal tubes is based on chest radiograph or CT
      scan measurements of the trachea or bronchus. Based on clinical reports, Univents
      or WEB blockers may be a better choice for patients with difficult airways who
      require one-lung ventilation or for when a selective lobar blockade is needed.
      For all selective intubation, the method of choice for proper tube placement and
      bronchial blockade is fiberoptic bronchoscopy with the patient in a supine
      position at first or in a lateral decubitus position later, or if a malposition
      occurs.

PMID- 11571903
TI  - Management of one-lung ventilation.
AB  - The practice of thoracic anesthesia requires a clear understanding of the
      techniques of lung separation and the technical skills necessary to apply such
      techniques. Customarily they are classified as absolute or relative.

PMID- 11571904
TI  - Anesthesia for airway surgery.
AB  - Surgery of the upper airway requires diagnostic or therapeutic manipulation of
      the respiratory tree despite ongoing ventilation. Whether internal or external
      access to the conducting airway is required, anesthesiologist and surgeon, who
      must work together closely, share the airway. The anesthetic technique is
      influenced by the chosen mode of ventilation.

PMID- 11571905
TI  - Whole lung lavage.
AB  - After more than 35 years of evolution, whole lung lavage is an efficient and safe
      technique. Furthermore, it can be a pleasant experience because it consists of
      performing general anesthesia without a surgeon being in the operating room.
      Whole lung lavage can be adapted to many patients and diseases; however, more
      research must be done to confirm the new indications.

PMID- 11571906
TI  - Anesthesia for patients with a mediastinal mass.
AB  - Anesthesia for patients with mediastinal masses carries a significant risk for
      fatal or near-fatal cardiorespiratory events. Careful history taking and thorough
      preoperative investigation, including CT, identify most susceptible patients.
      Preoperative fiberoptic bronchoscopy performed by or involving the
      anesthesiologist is invaluable for determining the plan for intubation and
      ventilation. A coordinated approach involving anesthesiologists and surgeons is
      essential.

PMID- 11571907
TI  - Lessons from lung transplantation for everyday thoracic anesthesia.
AB  - Patients with end-stage lung disease are at significant risk of hypoxia and
      dynamic hyperinflation during mechanical ventilation, particularly during one
      lung ventilation. This article describes aspects of care such as patients,
      including acceptance of permissive hypercapnia, adjustment of ventilator
      settings, and methods to optimize recovery from anesthesia.

PMID- 11571908
TI  - Anesthesia considerations for lung volume reduction surgery.
AB  - Patient selection is of crucial importance for outcome after lung volume
      reduction surgery. The anesthesiologist should be involved actively in patient
      selection, because he or she is in charge of the treatment during the critical
      perioperative period. Patient history and status and results from chest
      radiographs, high-resolution CT scans, and catheterization of the right heart
      should be taken carefully into account in the patient selection process.
      Promising new results involving functional parameters may predict outcome
      objectively after lung volume reduction surgery in the future. Careful selection
      and preoperative preparation of patients also are important to avoid
      complications and keep the success rate high. The anesthesiologist's
      understanding of the principles involved is important for the successful conduct
      of lung volume reduction surgery. It is unclear if lung volume reduction surgery
      is superior to conventional therapy in the long run because the decline in lung
      function is progressive after the procedure. A multicenter trial comparing
      patients undergoing lung volume reduction surgery with patients with emphysema
      who are treated conventionally hopefully will clarify this important question in
      the future.

PMID- 11571909
TI  - Post-thoracotomy analgesia.
AB  - Pain relief has come a long way in 20 years. Many aspects of the relief of pain
      of thoracic surgery must be rationalized and modernized to meet the demands
      placed on services and subject to new dynamics. To place the present state of
      practice and knowledge in the context of an anticipation that such attitudes will
      impact on and, ultimately, drive services for relief of pain, the key issues of
      safety, defining and measuring quality, and giving value for money must be
      addressed. Rationing is the impetus; the exercise to be conducted by those
      interested in the field of thoracic pain relief is to recognize that not all
      patients can have or require five-star services and gold standard techniques but
      are entitled to an equally high quality and measure of pain relief. Newer drugs,
      such as clonidine, ropivacaine, and modified local anesthetics, are on the
      horizon; old drugs, such as ketamine, are being revisited. Their place in the
      field will become apparent only if the ways that outcome measures are presented
      are more uniform and standard. Disaggregation analysis, pain profiling, a
      revisitiation of respiratory restoration factor, and optimization modeling are
      suggested ways forward to meet the clinical and organizationally holistic
      population forces being generated on the cusp of the third millennium.
      Increasingly, we live in a world defined by guidelines and protocols. The
      challenge is ensuring that these measure up to the watchwords--effective, safe,
      affordable.

PMID- 11571910
TI  - Interactions between perception and action in a reaction task with overlapping S
      R assignments.
AB  - We have used a novel task to study relationships between perception and action.
      Four experiments studied stimulus-response (S-R) relationships under conditions
      in which stimuli and responses were functionally unrelated (i.e., not assigned to
      each other by instruction) and merely overlapped in time. On each trial,
      participants carried out movements on a graphic tablet while observing motions
      displayed on a computer screen. The movement on trial n was specified by the
      motion observed on the previous trial n-1, whereas the motion observed on trial n
      specified the movement to be performed on trial n + 1. Results showed that
      stimulus motion had a contrast-like impact on response movement. Watching a small
      motion while performing a medium-sized movement increased movement size, whereas
      watching a large motion led to a decrease (Experiment 1). Further experiments
      showed that the contrast pattern was not affected by the mode of motion
      presentation (Experiment 2), or by the interval between motion and movement
      execution (Experiment 3). Contrast was also observed in the reverse direction,
      i.e., from action to perception (Experiment 4). We propose that the contrast
      effect is due to a mechanism for selective code modification. This mechanism acts
      to increase the distinctiveness of simultaneously activated perception and action
      codes in a common representational domain.

PMID- 11571911
TI  - Inferences about predictable events: eye movements during reading.
AB  - Eye fixations were recorded to assess whether, how, and when readers draw
      inferences about predictable events. Predicting context sentences, or non
      predicting control sentences, were presented, followed by continuation sentences
      in which a target word referred to a predictable event (inferential word) or an
      unlikely event (non-predictable word). There were no effects on initial target
      word processing measures, such as launch and landing sites, fixation probability,
      first-fixation duration, or first-pass reading time. However, relative to the
      control condition, the predicting context (1) speeded up reanalysis of the
      inferential word, as revealed by a reduction in second-pass reading time and
      regressions, and (2) interfered with processing of the non-predictable word, as
      shown by an increase in regressions. These results indicate that predictive
      inferences are active at late text integration processes, rather than at early
      lexical-access processes. The pattern of findings suggests that these inferences
      involve initial activation of rather general concepts following the inducing
      context, and that they are completed or refined with delay, after the inferential
      target word is read.

PMID- 11571912
TI  - Sequential analysis of a Simon task--evidence for an attention-shift account.
AB  - We investigated the attention-shift hypothesis of the Simon effect by analysing
      the effect of repeating relevant colour or irrelevant location of the stimulus in
      four serial reaction time tasks. In Experiment 1 with short response-stimulus
      intervals (RSI), we assume that there is no time to engage attention at the
      fixation cross before the onset of a new stimulus. In agreement with the
      hypothesis, Experiment 1 reveals no Simon effect when the stimulus location is
      repeated. In Experiment 2 with long RSI, we observe a Simon effect for location
      repetitions and alternations. In Experiment 3 with long RSI, we hinder the
      disengagement of attention by displaying the stimulus after response execution.
      As expected, the Simon effect is reduced for location repetitions. In Experiment
      4 with stimuli additionally presented at the fixation cross, responses are faster
      if the attention shift towards the centrally presented stimulus corresponds with
      the location of the required response. Additionally, we argue that binding of the
      stimulus features into an object or event file better explains the so-called
      blocking of the automatic response-priming route after a noncorresponding trial.

PMID- 11571913
TI  - The effects of onsets and offsets on visual attention.
AB  - Two experiments are presented which examine the effect of onset and offset cues
      on early occurring attentional cueing effects and later occurring inhibition of
      return (IOR). The first experiment compared the effects of single onset cues,
      single offset cues, and simultaneous onset and offset cues (at opposite
      locations) at a 100-ms stimulus-onset-asynchrony (SOA) and IOR at a 900-ms SOA.
      Whereas the first experiment examined these conditions with choice localization
      keypress responses, the second experiment used simple detection keypress
      responses. Both experiments found that onset and offset cues presented in
      isolation produce early facilitation and late IOR. When onset and offset cues
      were simultaneously presented, facilitation but not IOR was found with
      localization responses, while neither facilitation or IOR was found with
      detection responses. Overall, these findings suggest that offset cues can be
      treated in the same manner as onset cues by the attentional system, although the
      onset cues may have priority in orienting attention when targets must be
      localized in space.

PMID- 11571914
TI  - Task-set reconfiguration with binary and three-valued task dimensions.
AB  - Recently, we [Kleinsorge & Heuer (1999) Psychological Research, 62, 300-312]
      introduced the notion of generalizing switching operations to account for a
      characteristic pattern of shift costs that can be observed when participants have
      to shift between four tasks that result from an orthogonal combination of the two
      binary task dimensions kind of judgment (numerical vs spatial) and judgment-to
      response mapping (compatible vs incompatible). Specifically, while a change of
      the kind of judgment always results in costs, a change of mapping results in
      costs only when the kind of judgment is repeated, but results in benefits when
      the kind of judgment changes as well. In Experiment 1, we replicated and extended
      this finding with a combination of two spatial kinds of judgment that were more
      similar to each other and were more unlikely to result in build-in dependencies
      of the two task dimensions. In Experiment 2, we extended this design to a
      combination of nine tasks that resulted from a factorial combination of two three
      valued task dimensions. In this experiment, shift costs grew monotonically with
      the number of task dimensions on which a change took place. This outcome is
      consistent with the assumption that a generalizing switching operation is a
      forward-acting process that requires a specific target value to switch to.

PMID- 11571915
TI  - What happens when we relearn part of what we previously knew? Predictions and
      constraints for models of long-term memory.
AB  - Part-set relearning studies examine whether relearning a subset of previously
      learned items impairs or improves memory for other items in memory that are not
      relearned. Atkins and Murre have examined part-set relearning using multi-layer
      networks that learn by optimizing performance on a complete set of items. For
      this paper, four computer models that learn each item additively and separately
      were tested using the part-set relearning procedure (Hebbian network, CHARM,
      MINERVA 2, and SAM). Optimization models predict that part-set relearning should
      improve memory for items not relearned, while additive models make the opposite
      prediction. This distinction parallels the relative ability of these models to
      account for interference phenomena. Part-set relearning provides another source
      of evidence for choosing between optimization and additive models of long-term
      memory. A new study suggests that the predictions of the additive models are
      broadly supported.

PMID- 11571916
TI  - The time course of effort mobilization and strategic adjustments of response
      criteria.
AB  - In two-choice reaction time experiments, participants were instructed within a
      variable precueing interval to speed up responding in 20% of trials and to
      maintain their basic level of performance in the remaining trials. The
      achievement of this goal was rewarded by a monetary bonus. The requirement to
      speed up was signaled at varying intervals before the onset of the imperative
      stimulus. The main questions to be answered were whether participants would be
      able to dynamically adjust their response speed, and if so, whether a speed up
      would be due to enhanced effort with a genuine improvement of performance or due
      to an adjusted response criterion, accompanied by a speed-accuracy trade-off. The
      data of both experiments suggest that participants were able to invest some extra
      effort, the amount of which varied as a function of the length of the precueing
      interval. This speed-up was evident already in the fastest bins of the reaction
      time distribution, indicating a continuous modulation of processing efficiency.
      Only in the first experiment was there clear evidence for a speed-accuracy trade
      off in addition to effort mobilization.

PMID- 11571917
TI  - [Effect of acid-base imbalance on the equilibrium of elastase and its inhibitors
      in rat serum and aorta tissues].
AB  - In experiments on the acid-base imbalance modelling (acidosis induced with either
      lactate or ammonium chloride alcalosis induced with sodium hydrocarbonate) in
      rats, there were studied elastase activity, alpha-2-macroglobulin and alpha-1
      proteinase inhibitor contents in blood serum and tissues of the aorta. The
      results obtained indicated that, in the models of both acidosis and alcalosis an
      disbalance between elastase and its inhibitors was observed. However, in NH4CL
      acidosis in homogenates of aorta the inhibitors/elastase coefficient decreased at
      the expense of a reduction in contents of alpha-2-macroglobulin, while in lactate
      acidosis it only decreased at the expense of an increase in elastase activity. In
      alcalosis, contents of proteinase inhibitors were even increased, however a
      substantial increase in elastase activity indicated a reduction in integrative
      coefficient. Similar changes were observed in blood serum, except elastase
      activity was considerably elevated in NH4CL-acidosis and did not change in
      lactate-acidosis. Thus, an disbalance in the elastolytic system associated with
      different types of acid-base imbalance can promote the destruction of elastic
      fibers of aorta, which is considered as one of initial mechanisms in pathogenesis
      of arteriosclerosis.

PMID- 11571918
TI  - [Modulating effects of exogenous histamine, serotonin, and heparin on leukocytic
      reaction during inflammation].
AB  - On the model of E. coli-induced acute infectious peritonitis in rats previously
      depleted on mast cells of peritoneal cavity the replacing effects of various
      doses of exogenous histamine, serotonin and heparin and their complex on
      leukocytic reaction of inflammatory focus and blood were studied. In was shown
      that all of the used substances had a meaning in the mechanisms of modulating
      effect of mast cells on leukocytes. The analogous on direction to mast cells ones
      effects on leukocytes were produced mostly by histamine and especially by the
      complex of substances.

PMID- 11571919
TI  - [Changes in the local nonspecific immune response to post-traumatic inflammation
      during treatment].
AB  - Clinical investigation have been done in adult patients with broken mandible
      during 3 weeks of conservative treatment with aluminum splints (1st group, n =
      17) or steel splints (2nd group, n = 16) in comparison with health adults
      (control group, n = 18). The neutrophil emigration into alterative locus and
      their degranulation as well as phagocytic activity of peripheral blood
      neutrophils were tested. It was found that aluminum splint application caused the
      intensive inflammation and then the depression of local host defense reactions.
      Treatment with steel splints did not lead to neutrophil function depletion or to
      hyper-intensification of inflammatory reaction in patients. The increased values
      of neutrophil reactions were normalized in this group at the final period of the
      treatment. The examined trial ensures our accurate method in treatment of
      patients with broken mandible. The determination of local host defense state may
      be proposed as preferable simple express-method of evaluation of immune status,
      treatment efficiency and prognosis in these patients.

PMID- 11571920
TI  - [Brain research at the O. O. Bohomolets' Physiology Institute (1991-2001)].

PMID- 11571921
TI  - [Functional state of monocytes and some of their regulatory mechanisms during
      development of stress reactions].
AB  - In model researches on laboratory animals, reproducing experimental selective
      mielodepresion, is established, that at a realization in an organism of a
      unspecific stress-syndrome, in an outcome immobilization, in circulating
      neutrofiles the jet changes lysosomal of the vehicle determining increase in whey
      of activity some them lysosomal enzymes happen, that immediately can render
      influence to a series of parameters of functional activity monocytes of blood.

PMID- 11571922
TI  - [Structural-functional characteristics of the air-blood barrier of lungs upon
      inhalation of low concentrations of lead salt].
AB  - Under realization of electronmicroscopic investigation of respiratory department
      of lungs is shown, that in conditions of influence of low concentration of lead
      salts on the initial stages both intracellular, and ancellular processes caused
      stress influence on lungs and underlie the unspecific mechanism of lead action of
      lead had activated. The further influence of heavy metal results in adaptation of
      all systems to new conditions of functioning and is qualitatively new condition
      of a higher structurally functional level. On late stages accumulation of lead in
      lungs and its injuring action the picture of toxical alveolitis with the
      subsequent activation of collagen formation and development of interstitial
      fibrosis followed develops.

PMID- 11571923
TI  - [Effect of plant glycosides on snail neurons].
AB  - The effect of the plant triterpene saponins on Helix pomatia neurons is
      investigated. It was found that monodesmosidic saponins being perfused to the
      extracellular solution at concentrations 2[symbol: see text] 10(-3)-10(-4) M
      induced persistent hyperpolarization of the neurons. By using the patch-clamp
      technique it was obtained that these substances increased the amplitude of the
      outward potassium current. At lower concentrations (10(-5)-10(-7) M) saponins
      either led to the transient reversible oppression of the impulse activity, or
      didn't change the background activity. The influence of saponins is unspecific
      and develops during 1-2 min. It was supposed that the effect of triterpene
      saponins at high concentrations was related with the appearance of nonselective
      holes in neuron membrane.

PMID- 11571924
TI  - [Effect of monoamines and testosterone on hypothalamo-gonadal complex of Japanese
      quail (an electrophysiological and morphometric study)].
AB  - Effects of biogenic amines, testosterone and melatonin both on the developing
      electrical activity of hypothalamic arcuate nucleus (NA) and morphology of testis
      and NA neurocytes during maturation in birds (Coturnix coturnix japonica) were
      tested. Slow [symbol: see text]-frequency was shown to prevail at quail NA
      electrical activity. NA spectral power gradually enlarges during maturation. The
      data confirm the evidence that catecholamines induce acceleration of sexual
      maturation in birds mainly via brain alpha-adrenoreceptors, while dopamine- and
      serotoninergic brain systems cause deceleration of maturation. Morning or evening
      treatments with melatonin (5 mkg/100 g bw) and evening ones (50 mkg/100 g bw)
      were revealed to result in activation of hypothalamic-testicular axis, and high
      dose morning melatonin injections don't have any influence. Significant
      correlation was registered between the spectral power of NA neurocytes and
      profile area of their cellular nuclei. Total EA was demonstrated to vary at
      [symbol: see text]1- and, lesser, [symbol: see text]2-, [symbol: see text]-, and
      6-ranges of spectrum, and was insignificant at B-range.

PMID- 11571925
TI  - [Homeostasis indexes of staphylococcal anatoxin immunized blood donors,
      previously immunized with tetanus toxoid].
AB  - On the 50 volunteers from 20 to 40 years old gomeostasis indexes of inoculating
      by staphylococci cleaning adsorbing anatoxini donors, before have been
      revactinated against tetanus, were studied. It was established, that attract of
      plasmaferes donors to consistent immunization by tetani and staphylococci
      anatoxini don't call negative alterations in their gomeostasis indexes. Results
      of study demonstrate, that it's possibly to attract for immunization by
      staphylococci anatoxini donors, before have been revactinated against tetanus.

PMID- 11571926
TI  - [Absorption kinetics of C14-GABA and its vitamin B conjugates in isolated bovine
      retina].
AB  - Absorption by the bovine retina of physiological concentration of PLP-GABA
      increase clearing 2-32 minutes of incubation in difference of GABA and its non
      metabolic preparations, which store up as much as possible in first minutes:
      picamilon > PLP-GABA > GABA > panthogam > biotinil-GABA. Kinetics of transport of
      GABA and its preparations into retina has a complex character. By the growth of
      concentration from 33 mM to 528 mM, it is linear for picamilion, showing
      diffusion, and not linear for GABA, PLP-GABA and panthogam, showing differently
      systems of its transport. And only GABA transport is activated by Na-ions.

PMID- 11571927
TI  - [Regulation of innate immunity during xenogenic changes in blood circulation].
AB  - Calcium-dependent innate immune response with participation of the superfamily of
      immunoglobulins to several intra- and extracorporal xenobiotics were studied at
      216 recipients during synthetic cardiac valves implantation or veins
      transplantation in coronary arteries. It was shown that immediate immune response
      to xenobiotics was manifested by generation of the antitissue anodical
      autoprecipitin with specificity to the surface cell membrane component. This
      reaction initiated and regulated the subsequent dynamics of the two different
      fibrinogen autoimmune complexes formation, resulting in development of the
      immunogenic damages of blood circulation. Correction of these rapid innate immune
      responses is important for prevention and normalisation of the xenogenic damages
      of blood circulation during trans- and implantation on the heart impaired with
      endocarditis or aterosclerosis.

PMID- 11571928
TI  - [Oleh Oleksandrovych Bohomolets' would have been 90 years old].

PMID- 11571929
TI  - Growth hormone and sex steroids. Interactions in puberty.
AB  - Dynamic interactions among growth hormone, IGF-1, and sex steroidal hormones have
      a major role in the achievement of full height potential and the body composition
      changes in adolescence. Testosterone and estrogen affect the growth hormone
      neuroendocrine rhythms, and growth hormone, in turn, potentiates many of the
      metabolic actions of the sex steroids. Leptin is also thought to have a key
      regulatory role in the process of sexual development in the child, but the
      precise nature of these interactions is unclear. The targeted replacement of
      hormonal deficiencies in puberty and manipulation of the timing of pubertal
      maturation have resulted in better strategies to treat profoundly short children
      during this period; however, more research is needed to determine the
      consequences of such approaches in aspects of metabolism other than linear
      growth.

PMID- 11571930
TI  - Diagnosis and management of growth hormone deficiency in adults.
AB  - In adults, GHD is a clinical syndrome that occurs in patients with pituitary or
      hypothalamic disease. It may be asymptomatic or present with relatively
      nonspecific constitutional symptoms. Most patients have abnormal body
      composition, consisting of increased fat mass and decreased lean mass. Life
      expectancy is significantly decreased in hypopituitary patients with GHD, with
      cardiovascular disease a common cause of death. Treatment with growth hormone
      reverses abnormalities in body composition and may reduce cardiovascular risk
      factors; however, the long-term treatment outcomes regarding mortality, the
      incidence of cardiovascular disease, bone fractures, tumor development, and
      recurrence are not known. Longer prospective clinical studies are needed. The
      major manufacturers of growth hormone have initiated postmarketing surveillance
      databases to monitor the safety of growth hormone treatment.

PMID- 11571931
TI  - Acromegaly.
AB  - Acromegaly is a slow developing disease caused by hypersecretion of growth
      hormone and insulin-like growth factor 1. Increased morbidity and mortality
      associated with the disease make early diagnosis and treatment crucial. This
      article reviews the etiology, clinical manifestations, and diagnosis of
      acromegaly, with an emphasis on newly available therapeutic options.

PMID- 11571932
TI  - Disorders of prolactin secretion.
AB  - Prolactinomas are a common cause of reproductive/sexual dysfunction. Once other
      causes of hyperprolactinemia have been excluded with a careful history and
      physical examination, routine chemistries, and an assay for TSH, MR imaging, or
      CT will delineate the size and extent of the tumor. Medical therapy is the
      initial treatment of choice. When infertility is the primary indication for
      treatment, bromocriptine use has an extensive safety record and is preferred. For
      other indications, cabergoline seems to be more efficacious and better tolerated.
      Transsphenoidal surgery remains an option, especially for patients with
      microadenomas, when medical therapy is ineffective.

PMID- 11571933
TI  - Hypothalamic amenorrhea. The effects of environmental stresses on the
      reproductive system: a central effect of the central nervous system.
AB  - Although the treatment of anovulation has become significantly more specialized
      and complex in the centuries since Hippocrates, a complete understanding of the
      causes and mechanisms of hypothalamic amenorrhea has not been achieved. Even the
      best research on hypothalamic amenorrhea is plagued by the lack of longitudinal
      studies, the use of different exercise models, the difficulty of controlling for
      caloric intake, and the fact that genetics may have a role in the disorder.
      Continuing research on metabolic rate, leptin, and other factors will ultimately
      answer many of the outstanding questions and will help to create better tools for
      treating this disorder.

PMID- 11571934
TI  - Neuroendocrine aspects of aging in women.
AB  - In women, the loss of ovarian function at menopause is associated with marked
      changes in hypothalamic and pituitary function. In addition, the steady decline
      in serum levels of LH, FSH, and FAS with age following menopause provides clear
      evidence for age-related neuroendocrine changes independent of the changes
      occurring owing to loss of ovarian feedback on the hypothalamic and pituitary
      components of the reproductive axis. An increase in the overall amount of GnRH
      secreted occurs despite a 30% decrease in GnRH pulse frequency with aging. This
      observation implies that the amount of GnRH secreted with each secretory bolus is
      greater in older postmenopausal women when compared with younger postmenopausal
      women. Thus, there may be a prominent pituitary component to the age-related
      decline in gonadotropin secretion. Recent studies indicate that the response to
      estrogen negative feedback at the hypothalamic level is preserved with aging,
      whereas the response to estrogen positive feedback may decrease with reproductive
      aging; however, the response to estrogen positive feedback in women has not been
      investigated with respect to aging, per se. It will be important to determine
      whether these age-related changes in hypothalamic-pituitary function contribute
      to reproductive senescence in normal women, as has been suggested for similar
      changes in animal models.

PMID- 11571935
TI  - Neuroendocrine aging in men. Andropause and somatopause.
AB  - Aging is accompanied by gradual but progressive reductions in the secretion of
      testosterone and growth hormone in men, and by alterations in body composition
      and functional capacity that, to some degree, undo the effects of puberty.
      Preventing or reversing these changes with the use of trophic factors, including
      androgens, growth hormone, and growth hormone secretagogues, is an appealing
      prospect, but documenting the effectiveness of these interventions and their
      benefits and risks has proven to be a difficult undertaking that is far from
      complete. Small-scale clinical studies have shown that it is practicable to boost
      growth hormone and IGF-1 levels for periods of up to 12 months, and testosterone
      for up to 36 months, to reverse at least some age-related changes in body
      composition. Information regarding the effects of these interventions on
      strength, exercise capacity, and the ability to perform activities of daily
      living is still sparse, and additional reports from recently completed or
      currently ongoing clinical trials will not provide sufficient data to make firm
      conclusions. From the limited information currently available, androgen
      supplementation may be of benefit in some men aged more than 65 years,
      particularly in men with low serum testosterone levels (< 2 ng/mL). In this
      group, supplemental androgen therapy would be expected to increase lean body
      mass, bone mass, and possibly strength. In older men with testosterone levels
      between 2 and 3.5 ng/mL, some benefit might result from androgen supplementation,
      but it is not yet clear whether the benefits outweigh the risks. For men in this
      category, one might consider a 6- to 12-month trial of therapy after a full
      discussion and explicit consent, followed by a reassessment of the value of
      ongoing treatment. The even more limited data on growth hormone or growth hormone
      secretagogue interventions in aging do not support their general clinical use in
      healthy older men. Growth hormone is much more expensive than testosterone and is
      not covered by insurance for off-label uses. Patients who persistently seek a
      trial of therapy should be encouraged to enroll in a study if one is locally
      available. All of the growth hormone studies reported to date have focused,
      generally for reasons of safety, on healthy and robust groups of older subjects,
      men in whom the need for intervention is least compelling and in whom the
      functional effects of treatment may be the most difficult to observe. Phase II
      studies of intermediate size and duration examining prefrail groups of elderly
      who are at greater risk for functional loss and who stand to benefit the most
      from either preventive or restorative interventions are underway but are limited
      to the intermediate outcomes of body composition, strength, and function. Trials
      designed to assess clinically relevant final outcomes, such as falls, fractures,
      and institutionalization, are of necessity large-scale, long-term, and expensive.
      Support for larger phase III studies of growth hormone is unlikely to be
      forthcoming until the phase II studies are completed and show further promise. A
      multicenter clinical trial of testosterone is currently being planned under the
      joint sponsorship of the National Institute on Aging, the Veterans Health
      Administration, and industry, aimed at assessing the effects of testosterone on
      the risk for falls and fractures. The results of this trial and other large
      clinical trials should help to better define the balance of benefits and risks of
      trophic factor intervention in normal older men.

PMID- 11571936
TI  - Antidiuretic hormone. Normal and disordered function.
AB  - In humans and most other mammals, the antidiuretic hormone (ADH) is a nonapeptide
      often referred to as arginine vasopressin (AVP). It is produced by large neurons
      that originate in the supraoptic and paraventricular nucleus of the hypothalamus
      and project through the pituitary stalk to terminate on capillary plexuses
      scattered throughout the posterior pituitary. These plexuses drain into the
      systemic circulation by way of the cavernous sinus and superior vena cava.

PMID- 11571937
TI  - Neuroendocrinology of stress.
AB  - Stimuli that are interpreted by the brain as extreme or threatening, regardless
      of their modality, elicit an immediate stereotypic response characterized by
      enhanced cognition, affective immobility, vigilance, autonomic arousal and a
      global catabolic state. The brain's ability to mobilize this so-called stress
      response is paralleled by activation of corticotropin-releasing hormone (CRH) in
      several nuclei, including the hypothalamus, amygdala and locus ceruleus, and
      stimulation of the locus ceruleus norepinephrine (LC/NE) system in the brain
      stem. These systems perpetuate one another, interact with several other
      transmitter systems in the brain and directly activate the hypothalamic-pituitary
      adrenal (HPA) axis and the three components of the autonomic nervous system,
      namely the sympatho-adrenal, the cranio-sacral parasympathetic and the enteric
      nervous systems. The widespread body system responses to stress are discussed,
      and the implications of aberrant stress system activity on physical and mental
      health are outlined. Moreover, the promise of nonpeptide CRH type-1 receptor
      antagonists to directly target the stress system in the brain is highlighted.

PMID- 11571938
TI  - Diagnosis and differential diagnosis of Cushing's syndrome.
AB  - The clinical recognition of Cushing's syndrome and its biochemical confirmation
      is a challenging problem. The best diagnostic approach to patients with suspected
      Cushing's syndrome is still evolving. The traditional diagnostic approach of
      urine free cortisol and low-dose dexamethasone suppression testing may be
      inadequate when the degree of hypercortisolism is mild. Late-night salivary
      cortisol determinations may evolve as the simplest means of screening patients
      for suspected hypercortisolism. Repeated measurements of cortisol secretion
      (urine free cortisol or late-night salivary cortisol) over an extended period of
      time may be necessary to provide diagnostic certainty. The dexamethasone-CRH test
      is a reasonable approach in patients with equivocal data. The introduction of
      reliable, sensitive, and specific plasma ACTH measurements, the use of IPSS for
      ACTH with CRH stimulation, and the improved techniques of pituitary and adrenal
      imaging have made the differential diagnosis of Cushing's syndrome relatively
      straightforward (see Fig. 2). Clinicians who have never missed the diagnosis of
      Cushing's syndrome or have never been fooled by attempting to establish its cause
      should refer their patients with suspected hypercortisolism to someone who has.

PMID- 11571940
TI  - The neuroendocrinology of obesity.
AB  - The regulation of energy balance is enormously complex, with numerous genetic,
      hormonal, neural/behavioral, and societal influences. Although the current
      epidemic of obesity has its underpinnings in the changes in culture during the
      last half century, the role of the neuroendocrine system in the genesis of
      obesity is physiologically and therapeutically unavoidable. Increased
      understanding of this system has suggested organic etiologies (and therapies) for
      some rare and not-so-rare forms of obesity. With so many inputs, it is not
      implausible that dysfunction of other parts of this feedback system will be found
      to explain other forms of obesity in the future. Fortunately or unfortunately,
      diet and exercise remain the mainstays of obesity therapy. Most diet-exercise
      programs result in an acute 11-kg weight loss in adults; the question is whether
      it can be sustained without significant long-term behavior modification. In the
      European Sibutramine Trial of Obesity Reduction and Maintenance (STORM), 42% of
      treated patients dropped out; of those remaining, 77% of subjects lost more than
      5% of initial body weight, but only 43% of these individuals maintained greater
      than 80% of this loss over 2 years. Could there be an organic component in
      persons who do not respond? Obesity pharmacotherapies sometimes have beneficial
      acute effects, but these effects are impermanent; discontinuation tends to result
      in a rebound weight gain, suggesting that the etiology of the obesity is still
      present. A useful guiding principle is that patients who do not respond to diet
      and exercise should undergo an initial medical evaluation, including assessments
      of birth weight, past medical history, weight history, family history, diet,
      exercise, and fasting insulin and thyroid levels. As the nosology of obesity
      improves, diagnostic efficiency and therapeutic success should increase, leading
      to a decrease in associated morbidity, mortality, and socioeconomic
      ramifications.

PMID- 11571939
TI  - Neuroendocrine abnormalities associated with HIV infection.
AB  - Functional derangement of every endocrine organ system has been reported in
      association with HIV infection. The changes in endocrine function may be related
      to the viral infection of the gland, to systemic effects of HIV or an
      opportunistic infection, to infiltration by a neoplasm such as Kaposi's sarcoma,
      to a complication of treatment, or generation of cytokines. A wide spectrum of
      endocrine abnormalities is observed in HIV-infected patients. Some of these
      abnormalities are similar to those seen in other systemic illness, whereas others
      are unique to HIV infection. The clinical significance of many of these endocrine
      abnormalities is not well understood.

PMID- 11571941
TI  - Births, marriages, divorces, and deaths: provisional data for January 1999.

PMID- 11571942
TI  - Surgeon-patient barrier efficiency monitored with an electronic device in three
      surgical settings.
AB  - Blood-borne viral pathogens are an occupational threat to health care workers
      (HCWs), particularly those in the operating room. A major risk is posed by
      accidental penetrating injury, but skin contamination with body fluids from an
      infected patient, with prolonged intimate cutaneous contact, is a frequent
      occurrence during surgery, carrying further risk of transdermal infection. We
      have monitored barrier failure in three surgical settings (microsurgery,
      orthopedic surgery, general surgery) by means of an electronic surveillance
      device. A total of 111 surgical procedures were monitored: 67 microsurgeries, 22
      orthopedic surgeries, and 22 general surgeries. Of the 278 electronic alarms
      signaling barrier failure, 44 (15.8%) were associated with glove perforation, 39
      of which (88.6%) were not perceived by the operator. In 16 of those, the skin was
      visibly stained with the patient's blood. Altogether, 76 of the alarms (27.3%)
      were consequent to contacts caused by soaked gowns/sleeves, and 121 (43.5%) were
      attributed to hydration of latex porosities; 37 alarms (13.4%) were unexplained
      false positives. On only one occasion did a surgeon observe blood stains on his
      hands without a previous alarm; this event was classified as a device failure due
      to incorrect wiring. Double-gloving offered satisfactory protection against skin
      contamination during microsurgery but not during orthopedic surgery. The data
      presented here indicate that electronic monitoring of the surgical barrier
      enables prompt detection of barrier failure, especially at the level of the
      gloves, thereby limiting skin contamination with patients' body fluids during
      surgery.

PMID- 11571943
TI  - Surgeon's occupational exposure to nitrous oxide and sevoflurane during pediatric
      surgery.
AB  - Health hazards from occupational exposure to trace concentrations of anaesthetic
      gases cannot be definitively excluded. The aim of the study was to determine the
      surgeon's occupational exposure to nitrous oxide and sevoflurane during pediatric
      surgical procedures. Twenty young children (age < 10 years) and five teenagers
      (age > 10 years) underwent elective abdominal surgery under general inhalational
      anesthesia. The operating room was equipped with modern air conditioning and
      waste anesthetic gas scavenger. Levels of both nitrous oxide and sevoflurane were
      determined in the breathing zone of the surgeon and the anesthesiologist during
      the operative procedures by means of a direct-reading photoacoustic infrared
      spectrometer. Both the surgeon and the anesthesiologist were exposed to low
      concentrations of the inhalational agents used. Exposure to sevoflurane and
      nitrous oxide was clearly higher during surgery in young children than during
      operative procedures in teenagers. Nonetheless, the concentrations of these
      agents were well below the threshold limits of 25 ppm for nitrous oxide and 2 ppm
      for sevoflurane recommended by the National Institute of Occupational Safety and
      Health. General anesthesia results in operating room air pollution with
      inhalational anesthetics. Under modern air conditioning, personnel's occupational
      exposure is low, and inhalational anesthesia is safe from the standpoint of
      modern workplace laws and health care regulations. Nonetheless, all efforts must
      be taken to maintain occupational exposure at this low level.

PMID- 11571944
TI  - Mycotic aneurysm of common carotid artery induced by Staphylococcus aureus
      infection after cervical reoperation.
AB  - The objective of this study was to define a novel type of mycotic aneurysm of the
      carotid artery arising after cervical reoperation. We retrospectively analyzed
      all staphylococcal mycotic aneurysms of the common carotid artery. These
      aneurysms had developed after reoperative thyroid or parathyroid surgery,
      including resection of the central lymph node compartment and cervical
      reexploration. Mycotic aneurysms were found in three patients, with an incidence
      of 0.77% (2/261) and 0.62% (1/161) for thyroid and parathyroid reoperations,
      respectively. Postoperatively, a lymphatic fistula and cervical hematoma emerged
      in all patients, as did cervical wound infections on days 3, 4, and 6. Deep wound
      infections were noted on surgical revision. Cultures grew exclusively
      Staphylococcus aureus, which was resistant to methicillin (MRSA) in one patient.
      Mycotic aneurysms were identified 1 week after cervical reoperation. One aneurysm
      was discovered incidentally on planned lavage. The other two aneurysms presented
      as severe arterial hemorrhages, resulting in exsanguination in one patient. The
      other two patients had their aneurysms replaced by saphenous venous autografts.
      There seems to be accelerated arterial media destruction with formation of
      mycotic aneurysms in staphylococcal wound infections after cervical reoperation.
      It is important to recognize this novel type of mycotic aneurysm, as it must be
      repaired immediately to anticipate imminent rupture.

PMID- 11571945
TI  - Prognostic significance of synchronous and metachronous bilateral breast cancer.
AB  - Women previously treated for primary operable breast cancer are at increased risk
      of developing cancer in the contralateral breast, but the clinical significance
      of this development is unclear. The purpose of this study was to assess the
      impact of synchronous bilateral breast cancer or the development of a
      metachronous contralateral breast primary on the prognosis. In a series of 3210
      women age < or = 70 years treated between 1975 and 1995 for primary operable
      breast cancer, 106 were identified to have bilateral breast cancer. Of these
      women, 26 were noted to have synchronous bilateral breast primaries (0.8%), and
      80 developed a contralateral breast cancer after treatment for an initial primary
      breast cancer. Using life-tables analysis, there was a significant difference in
      survival between women with unilateral breast cancer, those with synchronous
      bilateral breast cancers, and those with metachronous contralateral breast with
      survivals at 16 years of 53.8%, 42.4%, and 60.1%, respectively (p < 0.0001), from
      the date of the diagnosis of the first primary tumor. There was no difference in
      survival seen between the three groups when survival was calculated from the date
      of diagnosis of the second primary in cases of metachronous contralateral breast
      cancer (p = 0.31). When contralateral breast cancer was incorporated as a time
      dependent covariate in a Cox multivariate model together with the three factors
      used to determine the Nottingham Prognostic Index (invasive tumor size, grade,
      and lymph node stage), contralateral breast cancer continued to be a significant
      prognostic determinant (p = 0.02). The survival of women with synchronous
      bilateral breast cancer or metachronous breast cancers diagnosed within 2 years
      of the original primary was worse than those with unilateral disease. However,
      the time duration to metachronous contralateral breast cancer did not have
      prognostic significance in a multivariate model compared with the prognostic
      features of the original primary.

PMID- 11571946
TI  - Lesser curvature lymph node metastases with esophageal squamous cell carcinoma:
      implications for gastroplasty.
AB  - The creation of a gastric tube after subtotal esophagectomy includes resection of
      the lesser curvature and abdominal lymph nodes. The fundus rotation gastroplasty
      has been recently proposed as an alternative technique of reconstruction that
      preserves the vascular arcade of the lesser curvature. This study investigates
      the number of resected and metastatic lymph nodes associated with abdominal
      lymphadenectomy to assess the oncologic radicality of fundus rotation
      gastroplasty. In this prospective clinical trial a two-field lymphadenectomy was
      performed in 39 patients with squamous cell carcinoma of the esophagus. The
      abdominal lymphadenectomy included partial resection of compartment I (lymph node
      groups 1, 2, and 3) and compartment II (lymph node groups 7, 8, 9, and 11). A
      meticulous workup of the specimen allowed an exact classification of specific
      lymph node groups and their metastatic status. After two-field lymphadenectomy a
      total of 1170 lymph nodes (average 30.0) including 690 abdominal lymph nodes with
      an average of 17.7 per patient were resected. Metastatic disease was found in 27
      of 39 patients (pN1 69.2%), with metastatic growth in 116 of 867 resected lymph
      nodes (13.4%). Of the 27 pN1 patients, 21 had abdominal lymph node metastases.
      Metastatic lymph nodes at the lesser curvature (groups 1, 3, and 7) were detected
      in 11.7%, 16.7%, and 29.7% of the resected lymph nodes, respectively. Of the 21
      patients (85.7%) with abdominal lymph node metastases, 18 had positive lymph
      nodes at the lesser curvature. Squamous cell carcinoma of the esophagus is
      associated with a high rate of lymph node metastases at the lesser curvature and
      the left gastric artery. Therefore preservation of the lesser curvature and the
      left gastric artery for gastroplasty reduces the radicality regarding lymph node
      metastases.

PMID- 11571947
TI  - Analysis of predictive factors for recurrence after hepatectomy for colorectal
      liver metastases.
AB  - Hepatectomy for liver metastases from colorectal cancer has recently received
      general acceptance as a safe, potentially curative treatment. Most patients,
      however, die of recurrent disease after hepatectomy. The predictive factors for
      recurrence after first resection of liver metastases have not yet been clarified.
      The authors aimed to determine the factors that can predict recurrence,
      especially hepatic-only recurrence after hepatectomy for colorectal liver
      metastases. Seventy-six patients who underwent liver resection of colorectal
      metastases were studied retrospectively. Forty-seven (61.8%) of the patients had
      a recurrence. The patients' disease-free survival after first hepatectomy and the
      second recurrence sites were univariately and multivariately analyzed using 16
      clinicopathologic variables. Wall invasion, lymph node metastases, lymphatic
      invasion, venous invasion of the primary tumor, 24 months or longer disease-free
      interval after resection of the primary colorectal cancer, and bilateral liver
      metastases significantly influenced the disease-free survival (log-rank test: p <
      0.05). The multivariate analysis revealed that venous invasion of the primary
      tumor and bilateral hepatic metastases were independent risk factors for
      recurrence after hepatectomy. The liver was the only site of second recurrence in
      23 patients. Patients with lymph node metastases and venous invasion of the
      primary tumor had a significant difference between hepatic-only and extrahepatic
      recurrence after first hepatectomy (chi-square test or Fishers' exact test: p <
      0.05). Recurrence after hepatectomy was influenced more by factors associated
      with the primary colorectal cancer than factors surrounding the first liver
      metastases. Venous invasion of the primary colorectal cancer was the most
      important predictable factor for hepatic-only second recurrence.

PMID- 11571948
TI  - Limited value of positron emission tomography in treatment of pancreatic cancer:
      surgeon's view.
AB  - We aimed to assess, from a surgical point of view, the value of positron emission
      tomography (PET) in the routine preoperative diagnostic evaluation of a
      pancreatic mass. In particular, we were interested in PET's ability to
      distinguish a malignancy from a nonmalignant process and its impact on surgical
      decision making. We documented prospectively the results of preoperative
      ultrasonography, computed tomography (CT), endoscopic retrograde
      cholangiopancreatography (ERCP), and PET in terms of a correct diagnosis of
      malignancy in 103 patients. All patients underwent surgery at our department and
      had a complete histologic workup. We then related the preoperative findings to
      the intraoperative and histologic findings and analyzed the advantages and
      limitations of PET in comparison with conventional diagnostic techniques. Both CT
      and PET showed high sensitivities (82% and 84%, respectively) but rather low
      specificities (61%). ERCP showed good specificity at 83% but weak sensitivity at
      46%. The positive predictive value was higher than 80% for all methods, whereas
      the negative predictive value was around 60% at best. Both the CT and the PET
      diagnoses were wrong in 15% of the cases. In all cases with a false CT diagnosis,
      the results of the other conventional examinations provided sufficient evidence
      to indicate the need for surgical intervention. In all cases where PET gave
      misleading results, CT findings indicated the need for surgery. PET overlooked
      pT1 cancers in three of the patients. PET does not reliably prove or exclude
      malignancy in situations where conventional diagnostic procedures leave doubt as
      to the nature of a pancreatic mass. PET does introduce a new procedure-related
      spectrum of misinterpretations to the diagnostic process.

PMID- 11571949
TI  - Incidence of gastrointestinal complications in cardiopulmonary bypass patients.
AB  - Gastrointestinal complications after cardiac surgery are associated with a high
      mortality rate. Because of the absence of early specific clinical signs,
      diagnosis is often delayed. The present study seeks to determine predictive risk
      factors for subsequent gastrointestinal complications after cardiosurgical
      procedures. Within a 1-year period, a total of 1116 patients who had undergone
      open heart surgery with cardiopulmonary bypass were prospectively studied for
      gastrointestinal complications. To determine predictive factors, all case
      histories of the patients were analyzed. Of the 1116 patients, 23 (2.1%) had
      gastrointestinal complications during the postoperative period, 10 of whom had to
      undergo subsequent abdominal surgery. Of these 23 patients, 20 died. Early
      gastrointestinal complications, which occurred mostly on postoperative days 6 or
      7, consisted of bowel ischemia or hepatic failure. Late complications were
      gastrointestinal bleeding, pseudomembranous colitis, cholecystitis, and septic
      rupture of a spleen. The relative risk for abdominal complications after
      cardiopulmonary bypass was highly increased in association with (1) a cardiac
      index less than 2.0 l/min-1/(m2)-1, (2) postoperative onset of atrial
      fibrillation, (3) emergency surgery, (4) need for vasopressors, (5) need for
      intraaortic balloon counterpulsation, and (6) need for early redo thoracotomy due
      to surgical complications. All patients with necrotic bowel disease had elevated
      serum lactate levels. Furthermore, cardiopulmonary bypass and aortic clamping
      times were significantly prolonged in patients who developed gastrointestinal
      complications. A number of predictive factors contribute to the development of
      gastrointestinal complications after cardiopulmonary bypass surgery. Knowledge of
      these factors may lead to earlier identification of patients at increased risk
      and may allow more efficient and earlier interventions to reduce mortality.

PMID- 11571950
TI  - Penetrating chest wounds: 24 years experience.
AB  - Thoracic and thoracoabdominal penetrating wounds are frequently encountered in
      urban medical centers in the United States. This study was undertaken to
      determine the clinical characteristics and in hospital outcome of these injuries.
      This was a longitudinal, nonblinded study using the established standard of care
      of patients with penetrating chest trauma. It consists of an analysis of a
      consecutive series of 3049 patients treated at one trauma center between April
      1972 and March 1996. There were 1347 stab wounds and 1702 gunshot wounds.
      Antibiotic prophylaxis was administered to patients who underwent laparotomy or
      thoracotomy or who had lung contusion with hemoptysis (41.6%, 1296/3049). Of 3049
      patients, 196 had cardiac injuries. All of them underwent thoracotomy, and the
      mortality was 21.9%. In contrast, among 2853 patients without cardiac injuries,
      only 257 (9%) required thoracotomy; the mortality in this group was 1.5%.
      Patients with thoracoabdominal injuries (899/3049) had a mortality of 4.3%
      compared to 2.1% among those who had isolated chest injuries. The overall
      mortality was 2.8%. Of 1702 patients with gunshot wounds, 85 (5%) sustained
      transaxial injuries, with an overall mortality of 36.5%. The complication rate
      among the survivors was 6% with only 2.5% being infectious. We conclude that the
      mortality for noncardiac penetrating injuries of the chest is low. The presence
      of associated abdominal injuries increases the mortality twofold. More than one
      third of the patients with transaxial wounds die. Gunshot wounds of the heart
      result in higher mortality than stab wounds to the heart. The infection rate is
      low.

PMID- 11571951
TI  - Lateral approach to laparoscopic repair of left diaphragmatic ruptures.
AB  - Video-assisted repairs of traumatic diaphragmatic ruptures have been described
      where thoracoscopy or laparoscopy in the supine position were used. This study
      aims to validate a new lateral laparoscopic approach for left diaphragmatic
      repairs. Six consecutive patients were operated on for left diaphragmatic rupture
      using a lateral approach (Gagner's position). A series of 362 consecutive
      patients presenting with abdominal or thoracic trauma with or without
      diaphragmatic rupture over a 2-year period were reviewed retrospectively.
      Contraindications for immediate or delayed lateral laparoscopic approach were
      studied. The lateral approach provided complete visibility of the
      subdiaphragmatic space, easy reduction of herniated organs, easy thoracic
      inspection and cleaning, the use of low peritoneal pressure, full range of
      instrumental motion, and rapid diaphragmatic repair. No operative mortality or
      morbidity was noted. Altogether, 14% to 50% of the patients with diaphragmatic
      ruptures were candidates for immediate lateral laparoscopic repair. Associated
      spleen injury in 50% of the cases was the main contraindication. The lateral
      laparoscopic approach provides better exposure of the diaphragm on the left side
      and facilitates the diaphragmatic repair especially with a large herniation.
      Immediate repair is possible in selected cases (14-50%). There is no
      contraindication in case of delayed diagnosis.

PMID- 11571952
TI  - Hemithyroidectomy: long-term effects on parathyroid function--preliminary report.
AB  - Early hypocalcemia after thyroid surgery has frequently been reported, whereas
      data regarding long-term effects on calcium homeostasis are scarce. We have
      previously studied patients after hemithyroidectomy with an oral calcium load
      test and found normal parathyroid hormone (PTH) suppression. However, the 1,25
      dihydroxyvitamin D concentration was decreased and the phosphate concentration
      increased, implying parathyroid insufficiency. We therefore proceeded to
      investigate PTH secretion and suppression in 10 euthyroid patients subjected to
      hemithyroidectomy due to benign thyroid disease before and at 1 year after
      surgery. In addition, biochemical variables known to influence calcium
      homeostasis were analyzed. Basal, maximal, and total PTH secretion were unaltered
      1 year postoperatively. However, maximal PTH secretion was reached at a lower
      serum level of ionized calcium, and there was a tendency toward increased
      parathyroid sensitivity to ionized calcium. Furthermore, compared to
      preoperative, total serum calcium, 1,25-dihydroxyvitamin D, and free thyroxine
      (T4) concentrations were decreased at follow-up. Total serum calcium and 1,25
      dihydoxyvitamin D concentrations were decreased 1 year after hemithyroidectomy.
      These changes were not due to parathyroid insufficiency. Instead, our results
      imply increased parathyroid sensitivity to calcium and possibly reduced
      peripheral sensitivity to PTH.

PMID- 11571953
TI  - Hurthle cell tumor of the thyroid: analysis of 188 cases.
AB  - We reviewed 188 cases of Hurthle cell tumor of the thyroid (HCT) between 1982 and
      1996. There were 160 women and 28 men with a mean age of 51.8 years. Thirty-one
      of the patients had cancer, and the others had adenoma. Age, size of the primary
      tumor, and preoperative thyroglobulin level were not significantly different in
      the cancer and adenoma patients. The gender ratio, however, was significantly
      different (p < 0.05). Recurrent HCT was observed in three patients with adenoma.
      Two patients had subcutaneous recurrence (suspected implantation), and the other
      patient had recurrence in the residual thyroid gland. All patients with
      recurrence of adenoma underwent partial lobectomy at the initial operation. Three
      cancer patients had recurrent disease. Locoregional recurrence was observed in
      one patient and distant metastases in two patients (lung in one, lung and bone in
      one). One of the patients with distant metastasis died from the disease, and the
      other is alive with the disease. Tumor implantation was observed in patients with
      adenoma, so intraoperative handling of the tumor requires care. It also means
      that this tumor, even though benign, is aggressive in terms of proliferative
      activity. All patients with Hurthle cell tumor should be treated by total
      lobectomy at least. The outcome of the cancer patients was not as poor as in
      previous reports.

PMID- 11571954
TI  - Prospective, randomized, comparative study of Misgav Ladach versus traditional
      cesarean section at Nazareth Hospital, Kenya.
AB  - Cesarean section (CS) is the commonest major operation carried out in many low
      income countries. A new technique for CS, called the Misgav Ladach procedure, was
      evaluated in a randomized trial in Nazareth Hospital (Kiambu District, Kenya). A
      total of 160 patients were assigned to the Misgav Ladach procedure (n = 80) or to
      the traditional CS as performed in most rural hospitals in low income countries
      (n = 80). The two groups were analyzed by operating time, presence of infection
      and febrile morbidity, grade of postoperative pain, starting of fluid and solid
      alimentation, and development of incisional hernia and hypertrophic scar. The
      operating time of the Misgav Ladach procedure was significantly shorter. 20.4 (SD
      6.1) minutes versus 30.4 (SD 6.1) minutes (p < 0.001). A total of 5 wound
      infections (6.2%) were seen with the Misgav Ladach procedure versus 16 (20.0%) in
      the control group (p = 0.01). The number of analgesic doses required during the
      postoperative period were significantly less in the Misgav Ladach group: 1.3 (SD
      0.6) versus 1.9 (SD 0.7) ampuls of pethidine (p < 0.001) and 15.1 (SD 2.0) versus
      16.4 (SD 1.8) tablets of ibuprofen (p < 0.001). Incisional pain was significantly
      less in the Misgav Ladach group: Visual Analogue Scale score 3.0 (SD 1.5) versus
      4.9 (SD 2.0), p < 0.01. The patients in the Misgav Ladach group began drinking
      fluids voluntarily [19.1 (SD 4.5) hours versus 20.6 (SD 4.0) hours; p = 0.01] and
      eating solid food [41.2 (SD 9.3) hours versus 46.1 (SD 9.0) hours; p < 0.01]
      significantly before than those in the control group. At the 6-week follow-up,
      the presence of hypertrophic scar was significantly associated with the
      traditional procedure (2.1% vs. 48.8%; p < 0.001). We conclude that the Misgav
      Ladach operation should become the standard method for performing CS in low
      income countries, particularly in rural hospitals.

PMID- 11571955
TI  - Advances in management of neurosurgical trauma in different continents.
AB  - Neurotrauma is a major public health problem. The incidence varies from 67 to 317
      per 100,000 and mortality rates are in the range of near 1% for minor injury, 18%
      for mild injury, and 48% for severe head injury. It is the main cause of death
      and disability in people under 40 years old. Several problems appear when outcome
      measurements, rehabilitation programs and treatment options are considered. In
      order to solve these problems a worldwide campaign is outlined. It focuses on
      epidemiology, prevention, education, treatment, rehabilitation, social re
      insertion, and outcome measurements. The goals of such a program are to take into
      account realities in both developed and developing countries, to develop
      worldwide acceptable programs and guidelines, and to test those guidelines and
      programs and diminish mortality and morbidity, improving quality of life. We
      describe the concept of Centers of Excellence and an educational program,
      Advanced Brain Life Support. Such a program is a moral obligation because
      mortality and morbidity tend to decrease in Centers of Excellence.

PMID- 11571956
TI  - Advances in management of neurosurgical trauma: USA and Canada.
AB  - Traumatic brain and spinal cord injuries continue to pose serious challenges for
      physicians around the world. In North America, the annual number of serious head
      and spinal injuries has decreased over the last two decades, and of those
      patients who reach a hospital, the mortality and long-term morbidity have also
      declined. The two major reasons for this reduction in death and disability after
      craniospinal trauma in the United States and Canada appear to be (1) widespread
      implementation of prevention measures, safety legislation, and public education
      initiatives; and (2) further improvements in and wider availability of emergency
      medical systems and regional trauma centers. Improvements in neurocritical care
      and the implementation of evidence-based treatment guidelines for severe head
      injury victims may also, in part, be responsible for improved survival rates and
      reduced disability rates. Unfortunately, numerous clinical trials of putative
      neuroprotective agents conducted in North America and elsewhere during the 1990s
      have failed to demonstrate efficacy in head-injured patients. However,
      methylprednisolone does appear to confer some benefit to a select population of
      spinal cord injury patients. These advances in the areas of prevention, regional
      trauma systems, treatment guidelines, and neurocritical care that have influenced
      survival rates and recovery of function are discussed.

PMID- 11571957
TI  - Guidelines for neurosurgical trauma in Brazil.
AB  - This chapter emphasizes some aspects of the Brazilian Guidelines for the
      Assessment of Head Injury Patients, written based on the experience of the
      Emergency Service, Neurosurgical Division of the University of Sao Paulo Medical
      School Hospital, and sponsored by the Brazilian Society of Neurosurgery. These
      guidelines approach the management of head-injury patients from their initial
      assessment in the Emergency Room until the final suggested clinical or surgical
      management. The Brazilian Guidelines represents our efforts to provide the basis
      for a common unified data collection system, which may allow cooperative studies
      in the future.

PMID- 11571958
TI  - Neurosurgical trauma in People's Republic of China.
AB  - An epidemiological investigation for neurological disorders was conducted in the
      People's Republic of China in 1983 and 1985. The incidence of traumatic
      neurological injury was 55.4 patients per 100,000 population in the six big
      cities and 64.1 patients in the 21 rural areas. The mortality rates were 6.3 per
      100,000 population (male:female = 1.7:1.0) in the six cities and 9.7 (m:f =
      2.5:1) in the rural areas. In the cities, the causes of brain injury were vehicle
      accidents (31.7%), followed by assaults (23.8%), falls (21.8%), stumbles (15.4%),
      and others. Brain concussion was 68.4%, contusion was 26.0%, and intracranial
      hematoma was 5.6%. The incidence of spinal cord injury was 0.67 per 100,000
      population in Beijing and 1.37 in Shanghai. Male versus female ratio was 7 to 1
      and the peak incidence was found in ages from 20 to 30 years old. In the past
      decade, vehicle accidents increased along with the increasing number of cars and
      motor bicycles. As a result of a series of administrative measures, such as
      improvement of traffic control and safe-driving education, mean mortality
      decreased from 33.4 per 10,000 motor vehicles in 1990 to 22.0 in 1995. It has
      been estimated that approximately 50,000 to 60,000 people die from vehicle
      accidents per year. Among these cases, brain injury accounts for 39% to 57% and
      spinal cord injury about 10%. Since vehicle accidents are the most common cause
      for neurotraumatic death, an effort is needed to prevent and to decrease the
      incidence of these accidental traumatic injuries.

PMID- 11571959
TI  - Neurosurgical trauma in Japan.
AB  - According to the statistics compiled by the Institute for Traffic Accident
      Research and Data Analysis, the total number of head trauma patients has stayed
      virtually the same for the last 10 years in Japan, although a fraction of people
      suffering minor head trauma has shown a trend to increase. The Japan Society of
      Neurotraumatology is in the process of establishing a guideline for head trauma
      management. No major difference is noted in surgical procedures selected by
      neurosurgeons in Japan as compared to those in other countries. It appears,
      however, that the ventriculostomy may be less frequently employed to control
      elevated intracranial pressure, and the jugular bulb venous oximetry is far more
      frequently employed to detect cerebral deoxygenation in Japan. There appear to be
      two obvious differences in selection of pharmacological therapies among
      neurosurgeons in Japan and those in other countries; neurosurgeons in Japan
      prefer glycerol to mannitol for osmotic control of intracranial pressure, and
      barbiturate to morphine as sedatives. Two drugs are currently available in Japan
      for promoting the recovery from disturbance of consciousness after head trauma:
      cytidine diphosphate choline (CDP)-choline (Nicholin, Takeda Chemical Industries,
      Ltd., Osaka) and protirelin tartrate (Hirtonin; thyrotropinreleasing hormone
      (TRH) analogue, Takeda). Another TRH analogue, NS-3 (montirelin hydrate), is
      currently submitted to the Ministry of Health and Welfare for approval. A multi
      institutional controlled study to examine the efficacy of therapeutic hypothermia
      for head trauma management is now in progress in Japan. The Japan Neurotrauma
      Data Bank System was inaugurated 2 years ago, enabling joint statistical
      processing at 10 major neurotrauma centers. Utilizing such a system, more
      detailed analysis of head trauma management will be possible, and clinical trials
      will be conducted systematically and more promptly in future.

PMID- 11571960
TI  - Head injury in the United Kingdom.
AB  - This paper reviews aspects of head injury management and research in the United
      Kingdom (UK). We discuss evidence about the scale and etiology of head injury in
      Britain and how this information has supported a triage-based approach,
      incorporating risk analysis. A Cohesive organization based upon nationally
      accepted, yet regionally flexible head injury management guidelines is important.
      Research in the United Kingdom has clarified the effect of head injury on the
      brain and how this can be reduced. This clarification follows from improved
      understanding of the neurobiology of injury, of secondary damage and recovery,
      and information gained from new techniques aimed at investigating events in
      patients. Outcome is an important perspective and we highlight the increasing
      focus upon recovery and the extent of disability after so called mild head
      injury. Although we retain a UK perspective, comparisons with aspects of European
      head injury emphasize the increasing importance of an international approach in
      the future.

PMID- 11571961
TI  - Present status of neurosurgical trauma in Germany.
AB  - Exact epidemiological data on head injury in Germany are limited and based on
      data from death certificates, the Federal Board of Statistics (Bundesamt fur
      Statistik), small regional cohort studies, and health insurance. With a
      population of 82 million people there had been 279,029 head injuries admitted to
      hospital in Germany in 1996. The majority had the diagnosis. "concussion," which
      refers to completely reversible lesions. Head injury caused the deaths of 9415
      patients in 1996, which amounts to a mortality of 11.5 per 100,000 inhabitants.
      At the same time there were 135 independent neurosurgical units, all of which had
      a computerized tomography scanner available. Of all fatal cases, however, 68.4%
      died before they reached a hospital. The exact cost is difficult to assess,
      because head injury causes more costs than only the hospital stay and
      rehabilitation.

PMID- 11571962
TI  - Advances in neurotrauma in Australia 1970-2000.
AB  - The management of neurotrauma in Australia has been one of the significant public
      health triumphs during the last 30 years of the 20th century. State and national
      government agencies act in a coordinated fashion to collect data and to promote
      research or how to manage neurotrauma patients. Between 1970 and 1995, fatalities
      from road accidents decreased by 47%. Hospital admissions have decreased by 40%
      despite a 40% increase in the population and a 120% increase in registered
      vehicles. Fatalities per 10,000 registered vehicles were 8.05% in 1970 and they
      fell to 1.84% per vehicles in 1995, while fatalities per 10,000 population were 3
      in 1970 falling to 1.11 in 1995. Hospitalization from road crashes decreased 23%
      between March 1988 and March 1997. Public education has steadily improved, backed
      by the state public health sources. A uniform code of road safety laws has been
      adopted, backed by legislation and legal penalties and increasing police
      enforcement. Clinical care of patients has improved as a result of faster
      communications, tele-medicine, trauma systems, the CT scanner, intensive care
      units, and improved monitoring. Patient rehabilitation and counseling are now
      carried out at units accredited by the Australian Council on Health Care
      Standards.

PMID- 11571963
TI  - Neurotrauma in Pakistan.
AB  - The incidence of head and spinal injury is on the rise in developing countries.
      The number of deaths and burden of disability may be reduced, if not completely
      stopped, through preventive measures after an epidemiological survey on trauma.
      The goal can be achieved to a significant extent through the use of guidelines
      from the countries that have achieved a reduction in the incidence of
      neurotrauma. To determine the incidence and outcome of neurotrauma in developing
      countries, a study was necessary using standardized assessment parameters for
      global interpretation. Such a study was conducted to determine the
      sociodemographic characteristics, morbidity, and mortality of patients with head
      and spinal injury admitted to various neurosurgical centers in Pakistan from July
      1, 1995 to June 30, 1999. A total of 260,000 patients were admitted with head
      injury over a 4-year period. The majority of patients presented during second
      decade (i.e., 33.2%) followed by first and third decade. There were 195,000 (75%)
      males, and 65,000 (25%) females with a ratio of 3:1. Road traffic accident was
      the commonest cause of head trauma. Mild, moderate, and severe head injury was
      observed in 135,200 (52%), 78,000 (30%), and 46,800 (18%) patients, respectively.
      Conservative management was carried out in 176,800 (68%) patients. Surgery was
      required in 83,200 (32%), 50% of which had depressed skull fracture, simple or
      compound. Follow-up period varied from 2 months to 2 years with a mean of 11
      months. Patient's outcome was assessed according to Glasgow Outcome Scale (GOS).
      Good outcome was observed in 174,200 (67%). The total mortality was 46,800 (18%).
      In this study, 2654 patients ranging in age from 5 to 70 years had spinal
      injuries. There were 1922 males (72%) and 732 (28%) females. British Medical
      Research Council Scale was used for assessment of motor power of patients with
      spinal trauma. Of these, 780 patients (29%) had complete spinal cord injury.
      Surgical intervention was performed in 1800 patients (68%) and the rest were
      managed conservatively.

PMID- 11571964
TI  - Pancreatectomy combined with superior mesenteric-portal vein resection for
      adenocarcinoma in pancreas.
AB  - The aims of this study were to investigate morbidity, mortality, and survival of
      patients with ductal adenocarcinoma of the pancreas who underwent pancreatectomy
      without (group 1) or with (group 2) en bloc portal vein resection and to study
      the degree of carcinoma invasion of the portal vein in group 2. The medical
      records of 46 and 28 patients in groups 1 and 2, respectively, were reviewed. In
      addition, the degree of invasion of the wall of the portal vein was categorized
      histologically into three types: type I, transmural invasion involving the
      intima; type II, invasion of the wall of the vein without intimal involvement;
      and type III, compression of the wall of the vein by surrounding carcinoma
      without true invasion. The morbidity and mortality in group 1 (26% and 4%) were
      not different from those in group 2 (32% and 4%). Similarly, there was no
      difference in survival between the two groups. Survival tended to vary directly
      with the depth of invasion of the wall of the portal vein: type I 6.8 +/- 1.9
      months; type II 15.3 +/- 6.4 months; type III 20.6 +/- 13.0 months. These
      findings suggest that en bloc resection of the pancreas and the portal vein does
      not increase mortality and morbidity after pancreatectomy; survival after en bloc
      resection was similar to that of patients not requiring portal vein resection.
      Combined resection of the pancreas with the portal vein could be an option in the
      treatment of pancreatic cancer with direct invasion of the portal vein.

PMID- 11571965
TI  - Preoperative chemoradiation therapy and anal sphincter preservation with locally
      advanced rectal adenocarcinoma.
AB  - Preoperative irradiation has been used to produce tumor regression and allow
      complete resection of rectal cancer with a sphincter-saving procedure. To
      evaluate the associated toxicity, the response in the primary tumor, and the
      postsurgical morbidity in a group of patients with locally advanced rectal cancer
      treated with preoperative chemoradiation therapy and low anterior resection, 120
      patients were treated with 45 Gy of preoperative radiotherapy and a bolus
      infusion of 5-fluorouracil 450 mg/m2 on days 1 to 5 and 28 to 32 of radiotherapy.
      Four to six weeks later, 16 lesions were found unresectable; 36 patients
      underwent abdominoperineal resection or pelvic exenteration, and in the remaining
      68 a low anterior resection was performed. For the purpose of this study only the
      latter group was included. There were 38 men and 30 women, with a mean age of
      54.7 +/- 13.1 years. Gastrointestinal and hematologic acute toxicity grade 3 to 4
      occurred in 12 and 7 patients, respectively. The mean distance of the tumor above
      the anal verge was 8.2 +/- 2.6 cm. In 10 patients the surgical resection included
      neighboring pelvic organs; 16 patients (23.5%) required a temporary diverting
      colostomy. The main causes of surgical morbidity were clinical anastomotic
      leakage in seven (10%), abdominal wall infection in five (7.4%), anastomotic
      stenosis in three (4.5%), and intraabdominal abscess in one (1.5%). No operative
      deaths occurred. The postsurgical stages were as follows: no tumor in the
      specimen, 17 (25%); T1, 4 (6%); T2, 12 (17%); T3, 17 (25%); T4, 5 (7%); any T
      with N+, 9 (13%); and any T, N with M+, 4 (6%). The median and mean follow-ups
      were 30.0 months and 37.4 +/- 25.0 months, respectively. The local recurrence
      rate was 2.9%, and the distant recurrence rate was 17%. The administration of
      preoperative chemoradiation therapy for locally advanced rectal cancer is
      associated with tolerable toxicity, a high rate of response in the primary tumor
      that allowed anal sphincter preservation, and a low rate of local recurrence.

PMID- 11571966
TI  - Ernst Ferdinand Sauerbruch: rise and fall of the pioneer of thoracic surgery.
AB  - Ferdinand Sauerbruch (1875-1951) was a pioneer of thoracic and cardiac surgery
      and is undoubtedly one of the twentieth century's most outstanding surgeons.
      Before 1904 operations on the thorax met with fatal complications due to
      pneumothorax. Sauerbruch developed a pressure-differential chamber that
      maintained normal respiration and enabled safe operations to be undertaken on the
      thorax. Together with von Mikulicz, he initiated intrathoracic operations and
      later developed various surgical procedures on the mediastinum, lungs,
      pericardium, heart, and esophagus. The simple yet effective techniques of
      positive-pressure ventilation replaced the expensive, cumbersome negative
      pressure chamber. Sauerbruch's latter years were marred by dementia that
      adversely affected his personality, intellect, and capacity as a surgeon. The
      unjustifiable toll of increasing patient morbidity and mortality forced
      authorities to dismiss him in 1949. He died at the age of 76 in Berlin. After
      almost a century since the advent of the first safe thoracic surgery, the
      advances in technique and technology have been enormous. A great deal is owed to
      the inspiration and contributions of Ferdinand Sauerbruch.

PMID- 11571967
TI  - Soft tissue injuries to face and neck: early assessment and repair.
AB  - The principles of assessment and repair of soft tissue trauma of the face are
      outlined. The importance of an adequate preoperative evaluation is emphasized.
      Recognizing lesions in the deep vital structures is extremely important in the
      initial approach to these patients. The postoperative care and the best
      management of the sequelae are described.

PMID- 11571968
TI  - Management of penetrating injuries to carotid artery.
AB  - The diagnosis and management of penetrating injuries to the cervical carotid
      arteries continue to be controversial. Most patients with stab or gunshot wounds
      to the common or internal carotid artery in cervical zone II (sternal notch to
      angle of mandible) are symptomatic with external or intraoral hemorrhage, a
      rapidly expanding hematoma, evidence of a carotid-jugular arteriovenous fistula
      at an obvious site, or loss of the carotid pulse with a neurologic deficit.
      Immediate airway control and arterial repair are indicated in such patients.
      Other patients present with stab or gunshot wounds with proximity only to the
      carotid sheath, a stable hematoma, unknown level of a carotid-jugular
      arteriovenous fistula, or loss of the carotid pulse without a neurologic deficit.
      Diagnostic options in this latter group include duplex ultrasound, color duplex
      imaging, and standard arteriography, while the role of CT or MRI angiography in
      evaluating patients with penetrating cervical wounds is unclear at this time.
      Certain arterial injuries discovered on diagnostic tests are currently managed
      with observation, endovascular stenting (for intimal or wall irregularities), and
      arteriographic embolization (for small pseudoaneurysms or high carotid-jugular
      fistulas). Operative repairs for injuries in zone II are performed through an
      oblique cervical incision and include all the options used with peripheral
      vascular injuries. Patients with penetrating cervical wounds, preoperative
      neurologic deficits, and immediate transport to the trauma center should have
      repair rather than ligation of the injured carotid artery. When the patient is
      truly comatose with a Glasgow Coma Scale score < 8, an unsatisfactory neurologic
      outcome is likely with either arterial repair or ligation. Injuries to the
      extracranial internal carotid artery in cervical zone III (above the angle of the
      mandible) may require innovative approaches to control hemorrhage and then
      maintain flow to the ipsilateral cerebral cortex.

PMID- 11571969
TI  - Blunt carotid and vertebral arterial injuries.
AB  - Blunt carotid and vertebral arterial injuries are uncommon but have the potential
      for devastating consequences. The classic presentation is a neurologic deficit
      unexplained by computed tomographic scan findings. Screening patients based on
      injury mechanisms and patterns allows the diagnosis and treatment of injuries
      while they are still asymptomatic, potentially improving neurologic outcomes. The
      development of a grading scale may help refine treatment guidelines. Accessible
      grade II, III, and V carotid injuries should be repaired surgically.
      Anticoagulation should be considered first-line therapy for grade I and IV, and
      inaccessible grade II and III carotid lesions, and grade I-IV vertebral injuries.
      Grade V and persistent grade III lesions may be best treated employing
      endovascular techniques.

PMID- 11571970
TI  - Cervical pharyngoesophageal and laryngotracheal injuries.
AB  - Aerodigestive tract injuries in the neck are found in about 7% of penetrating
      neck injuries and are very rare in blunt trauma. A combination of a good physical
      examination with endoscopy and esophagography can reliably diagnose all
      significant injuries. Airway control in laryngotracheal trauma is the most urgent
      priority and is often a difficult procedure. Although selected small pharyngeal
      and laryngotracheal injuries may be managed nonoperatively, all other
      aerodigestive tract injuries should be managed with early operation.

PMID- 11571971
TI  - Brachial plexus root avulsions.
AB  - The majority of adult brachial plexus palsies are posttraumatic injuries caused
      by high-energy forces, usually involving motor vehicles. In infants, brachial
      plexus palsies commonly represent obstetrical injuries following excessive
      traction on the plexus during complex or difficult delivery. Most adult injuries,
      and occasionally those in infants, represent brachial plexus root avulsion
      injuries that carry serious ramifications from the standpoint of permanent
      disability of a paralyzed extremity, prolonged recuperation, and significant
      socioeconomic impact. Modern-day management of root avulsions should focus on
      early, aggressive microsurgical reconstruction of the brachial plexus, combining
      various neurotizations with intraplexus and extraplexus ipsilateral and
      contralateral nerve donors, utilization of vascularized nerve grafts, and finally
      the use of free vascularized and neurotized muscles. When these multistage
      microsurgical management techniques are applied early (with complete avulsions)
      they may often result in significant return of neurologic function, especially in
      young patients. Amputation should be looked upon as an option only when these
      newer microsurgery techniques have failed.

PMID- 11571972
TI  - Post-traumatic cerebrospinal fluid leakage.
AB  - Posttraumatic cerebrospinal fluid (CSF) leakage frequently complicates skull base
      fractures. While most CSF leaks will cease without treatment, patients with
      persistent CSF leaks may be at increased risk for meningitis, and many will
      require surgical intervention. We reviewed the medical records of 51 patients
      treated between 1984 and 1998, with CSF leaks that persisted for 24 hours or
      longer after head trauma. Twenty-eight patients (53%) had spontaneous resolution
      of the leakage at an average of 5 days. Twenty-three patients (47%) required
      surgery. Eight patients (16%) had occult leaks presenting with recurrent
      meningitis at an average of 6.5 years posttrauma. Forty-three (84%) patients with
      CSF leaks had an associated skull fracture, most commonly involving the frontal
      sinus, while only 18 patients (35%) had parenchymal brain injury or extra-axial
      hematoma. Eight patients (16%) had delayed leaks at an average of 13 days
      posttrauma. Among patients with clinically evident CSF leakage the frequency of
      meningitis was 10% with antibiotic prophylaxis, and 21% without antibiotic
      prophylaxis. Thus, prophylactic antibiotic administration halved risk of
      meningitis. A variety of surgical approaches was used, with minimal morbidity.
      Three of 23 surgically treated patients (13%) required additional surgery for
      continued leakage. Patients with CSF leaks that persist greater than 24 hours are
      at risk for meningitis, and many will require surgical intervention. Prophylactic
      antibiotics may be effective and should be considered in this group of patients.
      Patients with skull fractures involving the skull base or frontal sinus should be
      followed for delayed leakage. Surgical outcome is excellent.

PMID- 11571973
TI  - Free vascularized bone grafts for reconstruction of traumatic bony defects of
      mandible and maxilla.
AB  - Small bone defects of the mandible and maxilla can be surgically treated with
      conventional bone grafts provided local conditions are optimal for bone healing.
      However, when the bone defect is large, is associated with soft tissue loss, or
      when conventional bone grafting fails, a free vascularized bone graft often
      becomes an important alternative to ensure adequate healing. As free vascularized
      bone grafting is today considered a more reliable procedure for bone
      reconstruction, with success rates over 96%, we prefer to treat even smaller
      segmental bone defects with this technique when local conditions are less than
      ideal. The technique also allows for simultaneous insertion of osteointegrated
      dental implants at the time of vascularized bone grafting, thereby facilitating
      earlier total oral rehabilitation.

PMID- 11571974
TI  - Endoscope-assisted facial fracture repair.
AB  - We describe the use of an endoscope-assisted technique for nasal osteotomy and
      mandibular fracture repair. The endoscopic visual enhancement has been especially
      helpful in making osteotomy safe and accurate as compared to the drawbacks
      associated with conventional blind osteotomy. The technique of endoscopically
      assisted fracture repair of the mandible facilitates anatomic restoration and
      fixation of the displaced condyle with limited-access incision. Under optical
      endoscopic magnification, the disadvantages associated with open surgical repair
      including the risk of facial nerve injury and external facial scarring are
      minimized. No postoperative complications have been attributable to the
      endoscopic approach.

PMID- 11571975
TI  - Orbital and optic nerve trauma.
AB  - The ability to measure orbital volume expansion and correlate this with later
      enophthalmos has advanced radiological assessment of patients with orbital floor
      fractures. Attempts have also been made to classify orbital floor fractures on
      the basis of their configuration on CT scan and to correlate this with outcome in
      terms of ocular motility. A small subset of relatively undisplaced floor
      fractures with tight entrapment of tissues occurring most commonly in young
      patients has been identified, and early surgical intervention has been
      recommended for these. The range of alloplastic materials available for orbital
      rim and wall fractures has increased, and complications related to various
      alloplastic implants continue to be reported. Optic nerve trauma has received
      considerable attention but remains a difficult management area. Recent literature
      on this subject shows no definite benefit for optic nerve decompression or high
      dose corticosteroids, although no prospective randomized study has been possible.

PMID- 11571976
TI  - Evaluation of cervical spine in intensive care patients following blunt trauma.
AB  - The aim of this study was to review a Level 1 trauma center's use of early (< 72
      hours from injury) limited MRI to "clear" cervical spine extradural soft tissue
      injuries in ICU patients sustaining blunt trauma. A retrospective review of the
      records of patients meeting entry criteria during 1997 was performed. Demographic
      data, cervical spine radiographic and imaging evaluation, results, and follow-up
      information were gathered. One hundred and fifty patients met criteria. Forty-one
      patients had initial static radiographs that revealed cervical spine trauma.
      Twenty-seven of the 108 patients with normal initial static radiographs had
      evidence of extradural soft tissue injury on MRI indicating potential spinal
      column instability. Twenty-one of the 108 patients had negative MRI and were
      liberated from cervical spine precautions at a mean of 2.9 +/- 0.9 days from
      injury. The remaining patients were cleared of cervical spine precautions by
      plain radiographs and reliable clinical examinations, or by dynamic radiographs,
      or they died before complete evaluation. The diagnosis of acute injury to the
      cervical spine from blunt trauma in ICU patients must include evaluation of the
      osseous spine and extradural soft tissues. Dynamic studies such as flexion and
      extension views place the obtunded ICU patient at risk of potential neurologic
      injury. MRI is a noninvasive imaging technique that allows evaluation of
      extradural soft tissue injury with potentially less patient risk and with fewer
      personnel. MRI allows early liberation of cervical spine precautions in those
      patients with negative studies. Further studies are needed to compare specific
      ligamentous injury patterns by MRI with dynamic studies of the C-spine to further
      define MRI injury patterns indicating risk of acute spinal instability.

PMID- 11571977
TI  - Silent cerebral infarction: risk factor for stroke complicating carotid
      endarterectomy.
AB  - "Silent" cerebral infarction is found in 20% to 30% of patients with significant
      internal carotid artery (ICA) disease. Our purpose was to determine whether such
      "silent" cerebral infarction in the operated carotid territory represents a risk
      factor for stroke during and immediately after carotid endarterectomy. Over 5
      years we followed a cohort of 663 patients with symptomatic and asymptomatic ICA
      stenosis who were consecutively scheduled for surgery. The stenosis was more than
      70% in patients with transient ischemic attacks and more than 95% in asymptomatic
      stenosis patients. All patients underwent preoperative computed tomography to
      determine the frequency, extent, and location of any "silent" cerebral
      infarction. Patients were grouped by the absence or presence of infarction in the
      operated carotid territory. Among the entire cohort, 20 patients had a major
      perioperative stroke (3.0%). All deaths were stroke-related. No intracranial
      bleeding occurred. Major stroke occurred in four (0.8%) patients without
      appropriate "silent" cerebral infarction, compared with 16 (8.8%) with an
      appropriate "silent" cerebral infarct (p < 0.001). After adjustment for
      confounding co-variables (e.g., gender, presence of preoperative symptoms, and
      age), "silent" cerebral infarction was found to be the only independent predictor
      of perioperative major stroke for symptomatic and asymptomatic stenosis (overall
      adjusted relative risk 11.5, 95% confidence interval 3.8-34.9, p < 0.0001).
      Patients with "silent" cerebral infarction seem to be at increased risk of
      perioperative stroke. Consequently, preoperative cerebral imaging is important
      for risk classification.

PMID- 11571978
TI  - Hypertonic saline in hydatid disease.
AB  - The objective of this study was to determine the scolicidal effects of saline in
      different concentrations using different exposure times and to examine whether
      hypertonic saline can be used to irrigate the abdomen when there is a free
      intraperitoneal perforation of hydatid disease. Various concentrations of saline
      solutions (0.09%, 3.0%, 6.5%, 10%, 15%, 20%, 25%, 30%) were added to concentrated
      echinococcus granulosus sediments for the following times: 1, 2, 3, 4, 5, 10, 15,
      30, 45, and 60 minutes. Normal (0.09%), 3.0%, and 6.5% saline resulted in high
      viability ratios after 60 minutes' exposure. Complete lethality for 10%, 15%,
      20%, 25%, and 30% saline occurred at the end of 75, 10, 6, 3, and 3 minutes,
      respectively. During the second part of the study, 20 Sprague-Dawley rats were
      used for abdominal saline irrigation in four groups: 30% NaCl for 3 minutes; 20%
      NaCl for 6 minutes; intravenous isotonic dextrose water and furosemide plus 30%
      NaCl irrigation for 3 minutes; the same prophylactic therapy plus 20% NaCl
      irrigation for 6 minutes. Sodium and chloride values rose significantly (20-30%)
      shortly after hypertonic saline irrigation in each group (p < 0.01). Support with
      isotonic dextrose and furosemide before irrigation did not have any beneficial
      effect on biochemical values or mortality. The 24- and 48-hour mortality rates
      were 70% and 90%, respectively. These studies illustrate that the scolicidal
      effect of hypertonic saline is limited in low concentrations, but an increase in
      the concentration can augment its adverse effects. Peritoneal irrigation with
      hypertonic saline should be avoided for intraabdominal perforated hydatid
      disease. Therefore, we concluded that hypertonic saline is not a good scolicidal
      agent to prevent recurrence of hydatid disease.

PMID- 11571979
TI  - Lactate metabolism during laparoscopic cholecystectomy: comparison between CO2
      pneumoperitoneum and abdominal wall retraction.
AB  - Recent reports have implicated CO2 pneumoperitoneum for laparoscopic surgery in
      the occurrence of postoperative mesenteric ischemia. With this kind of surgery,
      the increase in blood lactate levels has been attributed to anaerobic metabolism,
      probably due to tissue ischemia induced by high intraabdominal pressure (IAP).
      The aim of this study was to evaluate the metabolic repercussion of CO2
      pneumoperitoneum during laparoscopic cholecystectomy (LC). This was a prospective
      randomized study of CO2 pneumoperitoneum (PP group, n = 19) versus abdominal wall
      retraction (AWR group, n = 15). Demographic data were collected preoperatively.
      Four-trocar LC was performed with either a CO2 pneumoperitoneum (IAP of 12 mmHg)
      or abdominal wall retraction (abdominal wall pressure 6-10 kp). Intraoperative
      and postoperative blood samples were collected and lactate levels determined by
      enzymatic analysis. Repeated measures analysis of variance (MANOVA) was used for
      statistical analysis. Significance was evaluated at p < 0.05. The groups were
      shown to be homogeneous. Lactate concentration, expressed as mean (SD), went from
      25.4 (14.4) mg/dl at baseline to 18.9 (13.6) mg/dl 4 hours after surgery in the
      PP group and from 19.4 (6.1) mg/dl at baseline to 17.8 (14.7) mg/dl in the AWR
      group. No significant differences were found between groups intraoperatively (p =
      0.116) or postoperatively (p = 0.99). Our study did not show significant
      differences in blood lactate levels during LC with CO2 pneumoperitoneum compared
      to the same procedure with abdominal wall retraction.

PMID- 11571980
TI  - Indications for early postoperative intraperitoneal chemotherapy of advanced
      gastric cancer: results of a prospective randomized trial.
AB  - Previous analysis of this prospective randomized trial and meta-analysis of
      published randomized trials of adjuvant intraperitoneal chemotherapy demonstrated
      improved survival in patients with advanced gastric cancer. Simple criteria
      applicable at the time of surgery for patient selection were sought in this
      analysis. From 1990 to 1995 a series of 248 patients with biopsy-proven gastric
      cancer were randomized intraoperatively to receive early postoperative
      intraperitoneal mitomycin C and 5-fluorouracil (125 patients) versus surgery only
      (123 patients). Gastric resection plus early postoperative intraperitoneal
      chemotherapy showed improved overall survival compared to surgery only (54% and
      38%, respectively; p = 0.0278). There were statistically significant differences
      in patients with stage III (57% and 23%, respectively; p = 0.0024) and in those
      with stage IV (28% and 5%, respectively; p = 0.0098) gastric cancer. The
      improvement in survival rate was statistically significant for the subgroup of
      patients with gross serosal invasion (52% and 25%, respectively; p = 0.0004) and
      patients with lymph node metastasis (46% and 22%, respectively; p = 0.0027). The
      surgeons' impression about lymph node status was unreliable, but assessment of
      serosal invasion was accurate in 80% of cases. Gross serosal invasion with or
      without frozen section evaluation of lymph nodes can be used as the major
      selection criteria for early postoperative intraperitoneal chemotherapy of
      advanced gastric cancer.

PMID- 11571981
TI  - Characteristics of multicentric hepatocellular carcinomas: comparison with
      intrahepatic metastasis.
AB  - Characteristics of multicentric hepatocellular carcinomas (HCCs) remain obscure.
      We therefore aimed to clarify them and compare them with HCC with intrahepatic
      metastases. A series of 118 patients who had definite hepatitis C viral status
      and multinodular HCC were divided into two groups: a multicentric occurrence (MO)
      group (n = 38), with multicentric HCCs; and an intrahepatic metastasis (IM) group
      (n = 80), with HCC having intrahepatic metastases. Clinicopathologic variables,
      including the patient's survival and disease-free survival rates, were compared
      between the MO and IM groups. Univariate analysis revealed the presence of
      esophageal varices, the presence of hepatitis C virus infection, a platelet count
      of less than 10 x 10(4)/microliter, hepaplastin test, gamma-globulin, the
      histologically active hepatitis, tumor size, des-gamma-carboxy prothrombin > 0.1
      AU/ml, positive portal vein invasion, and histologic grade as discriminating
      factors. The MO score to differentiate multicentric HCCs from intrahepatic
      metastatic HCCs was determined using the following four independent factors
      selected by a stepwise regression analysis: the presence of hepatitis C virus
      infection, a platelet count of less than 10 x 10(4)/microliter, tumor size, and
      histologic grade. The sensitivity and specificity of the MO scores using those
      factors were 84% and 70%, respectively, when the cutoff value was 0.4. The
      disease-free survival rate in the MO group was similar to that in the IM group,
      whereas the survival rate in the MO group was significantly better than that in
      the IM group. The multivariate analysis revealed the multicentric occurrence of
      HCC as one of the independent prognostic factors. Clinicopathologic factors
      differentiating multicentric HCCs from intrahepatic metastatic HCCs were the
      presence of hepatitis C virus infection, a platelet count of less than 10 x
      10(4)/microliter, small tumor size, and low histologic grade.

PMID- 11571982
TI  - Genetic markers of survival and liver recurrence after resection of liver
      metastases from colorectal cancer.
AB  - A significant number of patients with liver metastases from colorectal cancer
      (CRC) achieve 5-year survival after liver resection. Increased expression of
      genetic markers in the primary tumor are known to predict outcome after colonic
      resection, but the predictive value of such markers after resection of hepatic
      metastases is unknown. The objective of this study was to evaluate whether DNA
      content and multiple genetic markers, separately or expressed together, can
      predict patient outcome (liver recurrence and survival) after resection of
      hepatic metastases. We studied the paraffin-embedded liver tissue of 71
      consecutive patients who had undergone a potentially curative resection of
      hepatic metastases from CRC. Using DNA flow cytometry and immunohistochemical
      staining techniques we determined the DNA content and the level of co-expression
      of seven tumor-associated proteins: proliferating cellular nuclear antigen
      (PCNA), epidermal growth factor receptor (EGFr), p53, c-erbB-2, H-ras, c-myc, and
      nm23. Three endpoints (liver recurrence, cancer specific, overall survival) were
      correlated with these tumor markers. The 5-year overall survival of the group was
      31.2%. There was no correlation detected between the DNA aneuploidy and overall
      or cancer-specific survival. Similarly, expression of the individual tumor
      associated proteins did not predict survival. Patients whose tumors co-expressed
      multiple markers had survivals similar to those whose tumors expressed fewer
      markers. However, a significant difference in hepatic recurrence was found
      between the p53-positive and p53-negative patients (p = 0.007), with marker
      negative tumors having decreased recurrence. In conclusion, this study
      demonstrates that the DNA content and genetic markers c-myc, c-erbB-2, EGFr, H
      ras, p53, PCNA, and nm23 do not predict survival after potentially curative
      resection of hepatic metastases from CRC. However, the immunoreactivity of p53
      may be an important marker of local recurrence in the liver, which may be useful
      if re-resection of metastatic liver tumors is considered a viable management
      option in this disease.

PMID- 11571983
TI  - [Movement of power].

PMID- 11571984
TI  - [Psychological help to cancer patients].

PMID- 11571985
TI  - [Increased worry about campylobacter infections].

PMID- 11571986
TI  - [Embolism as the cause of stroke].

PMID- 11571987
TI  - [Thrombotic or embolic stroke?].
AB  - BACKGROUND: Transoesophageal echocardiography reveals a possible source of
      embolism in many patients who present with acute brain ischaemia. The aim of this
      study was to observe the prevalence of possible sources of embolism in a
      representative Norwegian stroke population in a county hospital with a defined
      reference population. METHODS: All 103 patients with ischaemic stroke or
      transient ischaemic attack admitted to our hospital during a five-month period
      were enrolled. We performed transthoracic echocardiography in 98 patients,
      transoesophageal echocardiography in 83, and Doppler examination of the
      precerebral arteries in 92. RESULTS: Mean patient age was 72 years; 19 patients
      had atrial fibrillation. Examinations revealed 70 potential sources of embolism
      in 55 patients. Twenty-eight findings were in the heart. Five patients had
      thrombi in left-sided heart chambers. Ten patients had patent foramen ovale; 11
      had atrial septal aneurysm; four had both. Thirty-three had atheromas of the
      aorta with a protrusion of more than 4 mm, ten of them with mobile elements. Nine
      patients had carotid stenosis of high grade or carotid occlusion ipsilateral to a
      hemispheric stroke. INTERPRETATION: Potential precerebral sources of embolism are
      common in a representative population of patients with ischaemic stroke.
      Atheromas of the aorta may be an important contributor to brain ischaemia.

PMID- 11571988
TI  - [Early CT changes in acute cerebral infarction].
AB  - BACKGROUND: The aim of this study was to evaluate neurological clinical findings
      and cerebral computed tomography (CT) findings in patients with acute stroke
      within six hours after stroke onset. MATERIAL AND METHODS: 42 patients with
      presumed stroke in the middle cerebral artery territory were clinically assessed
      with the Scandinavian Stroke Scale Score. CT scans were assessed in a
      standardized manner by one neuroradiologist. RESULTS: The clinical deficit did
      not forecast the CT findings. Patients with several early CT signs of ischaemia,
      and especially those with hypodensity in less than one third of the middle
      cerebral artery area had lower clinical scores than patients with fewer signs.
      Hypodensity in the insular region was the overall most frequent finding.
      INTERPRETATION: Clinical findings do not give definite information about the
      ischaemic damage in the acute phase of cerebral infarction. CT scans may give
      valuable information primarily when there are positive findings.

PMID- 11571989
TI  - [Erythromycin and ciprofloxacin resistant Campylobacter jejuni].
AB  - BACKGROUND: Diarrhoea caused by Campylobacter is normally a self-limiting
      disease, but treatment with antibiotics may be indicated in very severe or
      complicated cases or in immunocompromised patients. This makes knowledge of the
      susceptibility of the Campylobacter to antibiotics important. MATERIAL AND
      METHODS: We examined retrospectively the in vitro susceptibility to erythromycin
      and ciprofloxacin of 296 C. jejuni strains isolated during the 1998-99 period.
      Particular attention was paid to the area in which the infection was acquired.
      RESULTS: Ciprofloxacin-resistant isolates were found in 69 (23%) of the patients.
      Among 121 patients probably infected abroad, the rate of resistance was 46%,
      highest among patients infected in Southern Europe (59%), followed by Asian and
      African countries. Such resistance was not recorded among strains acquired in
      Norway. Only one isolate showed resistance to erythromycin. A few strains showed
      intermediate susceptibility to both antibiotics. INTERPRETATION: During the 1998
      99 period, nearly one in four of all C. jejuni isolates in Sor-Trondelag County,
      Norway, were resistant to ciprofloxacin. Resistant isolates were acquired outside
      Norway. Resistance of C. jejuni to erythromycin occurred very rarely. In Norway
      erythromycin should still be the drug of choice in campylobacteriosis in cases
      where antibiotic treatment is indicated.

PMID- 11571990
TI  - [Immediate drug therapy of obstructive lung disease in hospital].
AB  - BACKGROUND: We have studied how patients with obstructive lung disease are
      treated in Norwegian hospitals and whether the treatment is in accordance with
      international guidelines. MATERIAL AND METHODS: During 76 days from 1 April 1997
      we registered all 176 patients (110 women) admitted for obstructive lung disease
      in two hospital catchment areas in western Norway. The medical treatment given
      the first three hours after admission was recorded by the doctors on call.
      RESULTS: 106 patients (60%) were above 65 years of age; 21 (12%) below 35.31% of
      the patients had a mild form of the disease, 42% a moderate, 21% a severe, and 6%
      a life-threatening condition. Almost all patients with moderate and severe
      disease were treated with beta 2 agonists on admission. Among the patients with
      moderate disease, 25% did not receive glucocorticoids during the first three
      hours in hospital. The proportion of patients treated with theophylline was lower
      among those with mild disease than among those with moderate disease (15% and 65%
      respectively). INTERPRETATION: Guidelines are followed to a high degree in
      patients with severe or life threatening obstructive lung disease, but only party
      in those with mild or moderate disease.

PMID- 11571991
TI  - [Skin biopsy for quantification of intraepidermal nerve fibers].
AB  - BACKGROUND: Skin biopsy for quantification of intraepidermal nerve fibre density
      has recently been introduced as a method for diagnosis of peripheral
      neuropathies. Immunostaining by antibody to protein gene product 9.5 has proved
      particularly useful because it selectively visualizes the epidermal nerve fibres.
      MATERIAL AND METHODS: We describe the procedure on the basis of relevant
      literature and our own experience. Results from investigations of 56 healthy
      individuals and three patients with small fibre involvement as part of their
      neuropathy are presented. RESULTS: In the healthy individuals, the mean density
      of epidermal fibres was 12.4 (SD 4.6), median 11.3 and range 6.0-26.1. Three
      patients with small fibre neuropathy had low intraepidermal nerve fibre density.
      INTERPRETATION: Skin biopsy for determination of intraepidermal nerve fibre
      density is a simple and non-painful procedure. Skin biopsies can be done
      repeatedly and may be used for the purpose of monitoring potential therapeutic
      agents.

PMID- 11571992
TI  - [Acute dystonia caused by metoclopramide (Afipran) therapy].
AB  - BACKGROUND: Metoclopramide is an antiemetic drug used frequently both in general
      practice and hospitals. The drug has few side effects, mainly drowsiness, and can
      be used both in pregnancy and breastfeeding. Acute dystonia is a rare side effect
      mostly affecting children and young adults within 1-3 days after start of the
      medication. Women are more frequently affected than men. MATERIAL AND METHODS: We
      present a clinical description of two patients admitted to our department with
      acute dystonia precipitated by metoclopramide. RESULTS: Both patients received
      treatment with biperiden; one received additional benzodiazepine. Both recovered
      rapidly and were discharged symptom free the next day. INTERPRETATION:
      Metoclopramide-induced dystonia is frightening both for the patient and the
      family. Because of concomitant anxiety and psychiatric symptoms, individuals are
      often regarded as hysterical. The attack can be abbreviated by parenteral
      administration of anticholinergic drugs. It is important that all doctors
      prescribing metoclopramide know of this side effect, especially when their
      patients are young females.

PMID- 11571993
TI  - [Can psychological treatment help patients with cancer?].
AB  - BACKGROUND: A number of studies have shown that psychological interventions may
      supplement the medical treatment of cancer patients by reducing psychological
      morbidity and increasing their quality of life. However, previous literature
      reviews point to methodological flaws limiting the specific and definite
      conclusions that can be drawn with respect to intervention effects. MATERIAL AND
      METHODS: Through searches in Medline, Embase and PsycINFO, the present study aims
      to review recent controlled studies from 1992-2000. RESULTS: Of the ten studies
      identified, seven reported effects of cognitive, psycho-educational and
      supportive treatment of various forms of cancer. INTERPRETATION: As found in the
      previous literature reviews, methodological shortcomings limit what firm
      conclusions may be drawn in order to guide clinicians as to what kind of
      interventions will be cost-effective for specific cancer patient groups.
      Nevertheless, the present as well as the previous reviews indicate that
      psychological treatment of cancer patients should be continued and that more well
      controlled studies should be conducted.

PMID- 11571994
TI  - [Periodic limb movements in sleep--can and should this condition be treated?].
AB  - BACKGROUND: Periodic limb movements in sleep (PLMS) may occur in up to 6% of the
      general population and is more common in the elderly. MATERIAL AND METHODS: Based
      on relevant literature and recent guidelines from the American Academy of Sleep
      Medicine, we present an overview of symptoms, diagnostic examinations and
      treatment of periodic limb movements in sleep, including its relation to restless
      legs. A short case history is also presented. RESULTS: Patients with periodic
      limb movements in sleep may or may not have other symptoms, such as insomnia and
      excessive daytime sleepiness. Polysomnography is necessary for the diagnosis.
      Only patients who meet specific diagnostic criteria should be treated
      pharmacologically. Our patient was examined by polysomnography and actigraphy
      before and during pharmacological treatment. INTERPRETATION: The concept and
      treatment of periodic limb movements in sleep is controversial.

PMID- 11571995
TI  - [Reduction of the use of habit-forming drugs in Vest-Agder].
AB  - BACKGROUND: For several years, the county of Vest-Agder has been over the
      Norwegian average for sales of habit-forming prescription medication. MATERIAL
      AND METHODS: A quasi-experimental project was implemented in an attempt to reduce
      prescription of habit-forming medication by general practitioners. 59% of
      eligible physicians participated in the ten-month project; 192 physicians were
      invited to participate, 114 accepted; 13 of these were excluded, primarily due to
      low weekly patient contact hours. All participating physicians received profiles
      of their own prescribing habits as well as the habits of other participating
      doctors in the region (anonymous). Physicians with a documented (via pharmacy
      registry) prescription rate of over 4,000 defined daily doses (DDD) per month
      were defined as heavy prescribers and offered a colleague-based counseling
      session regarding their prescribing habits. RESULTS: A comparison of heavy
      prescribers (n = 9) with other participating physicians (n = 92) revealed that
      after ten months, prescription of habit forming medication was reduced 8.5% in
      heavy subscribers, while the other participating physicians increased their
      prescription rates by 2.1%. The reduction in DDD observed among heavy subscribers
      was accounted for by reductions in both the number of prescriptions and the
      number of DDD per prescription. INTERPRETATION: Identification and feedback,
      rather than the colleague-based interview, seemed to be responsible for the
      reductions observed among heavy prescribers.

PMID- 11571996
TI  - [The radiotherapy satellite in Kristiansand--a model for Norwegian regional
      hospitals?].
AB  - BACKGROUND: During the first decade of 2000, significant increase of radiotherapy
      capacity in Norway will take place, as the number of linear accelerators will
      increase from 24 to 36. In Norway, radiotherapy departments are traditionally
      located only in university hospitals. However, six of the new accelerators will
      not be installed in existing radiotherapy centres, but in small, new radiotherapy
      units, set up in selected county hospitals and organized as satellites of the
      university hospitals, in order to secure the treatment quality. The university
      hospital is responsible for both medical and technical standards in the
      satellite, while the county hospitals have the financial responsibility. RESULTS:
      The satellite model combines two important aspects of hospital management;
      treatment is geographically decentralized, while treatment quality is
      centralized. The first radiotherapy satellite was established in the town of
      Kristiansand in January 2001. We report our experience with this new concept in
      radiotherapy. INTERPRETATION: The satellite model should be evaluated also for
      other medical specialties within the university hospitals.

PMID- 11571997
TI  - [Drug-induced rhinitis--significant adverse effect].

PMID- 11571998
TI  - [From planning to market--some perspectives on the hospital reform].

PMID- 11571999
TI  - [State hospitals--why?].

PMID- 11572000
TI  - [Efficient treatment of depressions is possible!].

PMID- 11572001
TI  - [Lamotrigine in neuropsychiatric diseases].

PMID- 11572002
TI  - [Encephalitis after acute Epstein-Barr virus infection].

PMID- 11572003
TI  - [Diagnosis of rotator cuff injury].

PMID- 11572004
TI  - [Quality of life].

PMID- 11572005
TI  - [Uncritical views on photodynamic therapy].

PMID- 11572006
TI  - [Extension of locum-tenency for women physicians after maternal leave].

PMID- 11572007
TI  - [Specialist education in obstetrics and gynecology].

PMID- 11572008
TI  - [Better teaching methods in Vestfold?].

PMID- 11572009
TI  - [The serial story about salary and career choice].

PMID- 11572010
TI  - [Cost-effective drug utilization--what can the national drug agency do?].

PMID- 11572011
TI  - Sunshine by cooling.
AB  - An overview of the development of cooler rings for fast ions with emphasis on
      electron cooling of heavy ion and radioactive beams is presented. Some of the
      most important discoveries made with the use of this new experimental tool
      include the first observation of string-like ordered ion beams, the development
      of Schottky mass spectrometry for precision mass measurements of radioactive
      nuclei, the discovery of bound-state beta-decay of highly ionized nuclei and the
      calibration of the Re/Os cosmochronometer including a determination of the age of
      our Galaxy. First results of 1 s-state hyperfine interaction, and Lambshift
      measurements in hydrogen-like heavy ions are presented, together with an outlook
      on ongoing developments.

PMID- 11572012
TI  - Forest ecosystem development in post-mining landscapes: a case study of the
      Lusatian lignite district.
AB  - The restoration of surface mining landscapes requries the (re)creation of
      ecosystems. In Lusatia (eastern Germany), large-scale open-cast lignite mining
      operations generated spoil dumps widely consisting of acidified, phytotoxic
      substrates. Amelioration and rehabilitation measures have been developed and
      applied to these substrates since the 1950s. However, it is still not clear
      whether these approaches are sustainable. This paper reports on collaborative
      research work into the ecological potential of forest ecosystem development on
      typical minesites in the Lusatian lignite district. At first sight, pine stands
      on minesites along a chronosequence comprising about 35 years did not show
      differences when compared with stands on non-mined sites of the general region.
      Furthermore, with some modification, conceptual models for flora and fauna
      succession in forest stands on non-mined sites seem to be applicable, at least
      for the early stages of forest ecosystem development. For example, soil organism
      abundance and activity at minesites had already reached levels typical of non
      mined sites after about 20-30 years. In contrast, mine soils are very different
      from non-mined soils of the test region. Chemically, mine soil development is
      dominated by processes originating from pyrite oxidation. Geogenic, i.e.
      lignitic, soil organic carbon was shown to substitute for some functions of
      pedogenic soil organic matter. Rooting was hampered but not completely impeded in
      strongly acidified soil compartments. Roots and mycorrhizae are apparently able
      to make use of the characteristic heterogeneity of young mine soils. Considering
      these recent results and the knowledge accumulated during more than 30 years of
      research on minesite rehabilitation internationally, it can be stated that
      minesite restoration might be used as an ideal case study for forest ecosystem
      development starting at "point zero" on "terra nova".

PMID- 11572013
TI  - Heteropteran chemical repellents identified in the citrus odor of a seabird
      (crested auklet: Aethia cristatella): evolutionary convergence in chemical
      ecology.
AB  - The exogenous application of chemical repellents is widespread in birds, but
      endogenous production is exceedingly rare. We herein report a new class of avian
      defensive compounds isolated from the feathers and volatile odor of the crested
      auklet (Aethia cristatella). Mass spectra indicate that n-hexanal, n-octanal, n
      decanal, Z-4-decenal and a 12-carbon unsaturated aldehyde comprise the auklet
      odorant. Octanal and hexanal are also secreted in the repugnant metasternal gland
      emissions of heteropteran insects and are known to be potent invertebrate
      repellents. We suggest that the auklet odorant functions as an ectoparasite
      repellent and a signal of mate quality. This would represent a rare and direct
      link between vigor, quality and parasite resistance, one of several putative
      bases for mate selection. This is the first report of defensive compounds
      produced by a seabird or colonial bird and one of the few examples of chemical
      defense in a polar or subpolar marine vertebrate.

PMID- 11572014
TI  - A pear-derived kairomone with pheromonal potency that attracts male and female
      codling moth, Cydia pomonella (L.).
AB  - Ethyl (2E, 4Z)-2,4-decadienoate, a pear-derived volatile, is a species-specific,
      durable, and highly potent attractant to the codling moth (CM), Cydia pomonella
      (L.), a serious pest of walnuts, apples, and pears worldwide. This kairomone
      attracts both CM males and virgin and mated females. It is highly attractive to
      CM in both walnut and apple orchard contexts, but has shown limited effectiveness
      in a pear orchard context. Rubber septa lures loaded with ethyl (2E, 4Z)-2,4
      decadienoate remained attractive for several months under field conditions. At
      the same low microgram load rates on septa, the combined gender capture of CM in
      kairomone-baited traps was similar to the capture rate of males in traps baited
      with codlemone, the major sex pheromone component. The particular attribute of
      attracting CM females renders this kairomone a novel tool for monitoring
      population flight and mating-ovipositional status, and potentially a major new
      weapon for directly controlling CM populations.

PMID- 11572015
TI  - Attractants from Bartlett pear for codling moth, Cydia pomonella (L.), larvae.
AB  - The alkyl ethyl and methyl esters of (2E,4Z)-2,4-decadienoic acid found in head
      space samples of ripe Bartlett pear (Pyrus communis L.) stimulated a response
      from neonate larvae of the codling moth (CM), Cydia pomonella (L.), in both
      static-air Petri-plate and in upwind Y-tube and straight-tube olfactometer
      bioassays. In comparison with the known CM neonate attractant, (E,E)-alpha
      farnesene, ethyl (2E,4Z)-2,4-decadienoate was attractive at 10-fold and 1,000
      fold lower threshold dosages in the Petri-plate and in the Y-tube bioassays,
      respectively. Methyl (2E,4Z)-2,4-decadienoate was attractive to CM neonates in
      these bioassays at much higher doses than ethyl (2E,4Z)-2,4-decadienoate. Other
      principal head-space volatiles from ripe pear fruit and pear leaves, including
      butyl acetate, hexyl acetate, (Z)-3-hexenyl acetate, and (E)-beta-ocimene, were
      not attractive to CM neonates. The potential uses of these pear kairomones for
      monitoring and control of CM in walnuts and apple are discussed.

PMID- 11572016
TI  - Seasonal patterns in the orientation system of the migratory ant Pachycondyla
      marginata.
AB  - Route directions of migrations by the neotropical termite-hunting ant
      Pachycondyla marginata at a forest reserve in Southeast Brazil were analysed by
      circular statistic. Colony movement patterns were compared between the rainy/hot
      and dry/cold seasons. Migrations during the dry/cold season are significantly
      oriented 13 degrees with the magnetic North-South axis, while rainy/hot
      migrations do not exhibit a preferred direction. This result is discussed
      considering the hypothesis that P. marginata ants may use the geomagnetic field
      as an orientation cue for migrations in the dry/cold season. The presence of
      magnetic iron oxides in the head and abdomen of P. marginata is consistent with
      this suggestion.

PMID- 11572017
TI  - Facultative and obligate slave making in Formica ants.
AB  - Here we show for the first time that the presumed facultative slave-making ant
      Formica subintegra does not activate outside its nest until July and August, when
      it raids slaves. A comparative behavioral study of seasonal and daily activities,
      retrieval of prey, and nest maintenance of F. subintegra, the obligate slavemaker
      Polyergus breviceps, and the facultative Formica subnuda, shows that the
      behavioral repertory of F. subintegra closely resembles that of P. breviceps and
      clearly differs from the repertory of F. subnuda. Unlike P. breviceps, F.
      subintegra has retained some nest-building activity which, owing to lack of
      competence, does not contribute to nest maintenance. We suggested earlier that F.
      subintegra is probably an obligate slavemaker, because it always has in its
      colonies a large proportion of slaves of the total workforce, whereas F. subnuda
      fares well even without slaves. This, coupled with no foraging in early summer
      and a raiding period later on, strongly suggests that F. subintegra is an
      obligate slave-making ant.

PMID- 11572018
TI  - Fungal bioturbation paths in a compact disk.
AB  - We report here on bioturbation traces, with micro-dendrite textures, composed of
      a mixture of altered aluminum and polycarbonate, which have been developed in a
      common compact disk (CD), destroying information pits. Fungal hyphae proliferated
      in these deteriorated zones, and Geotrichum-type fungus was isolated from surface
      sterilized CD fragments. The severe biodeterioration described is attributed to
      the slow growth of this arthroconidial fungus on the CD material in the tropical
      indoor environment of Belize, Central America (approximately 30 degrees C,
      approximately 90% humidity).

PMID- 11572019
TI  - Fluorodeoxyglucose positron emission tomography for detection of recurrent or
      metastatic breast cancer.
AB  - Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a noninvasive
      imaging technique capable of identifying primary tumors and metastases with high
      sensitivity and accuracy. The aim of this study was to evaluate the diagnostic
      accuracy of whole-body FDG-PET imaging for the detection of recurrent or
      metastatic breast cancer after surgery. Whole-body FDG-PET imaging was performed
      on 27 patients with suspected recurrent breast carcinoma. PET images were
      evaluated qualitatively for each patient and lesion. FDG-PET scans showed that
      there were 61 reference sites of malignant or benign lesions in 27 patients. In a
      patient-based analysis, FDG-PET scans correctly identified 16 of 17 patients with
      recurrent or metastatic disease and 8 of 10 without recurrence, resulting in a
      sensitivity, specificity, and accuracy of 94%, 80%, and 89%, respectively. In a
      lesion-based analysis, FDG-PET scans correctly identified 46 of 48 lesion sites
      with recurrent or metastatic disease and 11 of 13 without recurrence. The overall
      sensitivity, specificity, and accuracy for all lesion sites were 96%, 85%, and
      93%, respectively. FDG-PET scans revealed unsuspected recurrent or metastatic
      diseases in 8 of 27 (30%) of patients and 11 of 20 (55%) distant metastatic
      lesions. In 13 patients treatment was altered by the outcome of the PET scan. We
      concluded that whole-body FDG-PET scan is a useful diagnostic imaging modality
      for detecting recurrent or metastatic breast carcinoma in patients suspected of
      having recurrent disease after primary surgery.

PMID- 11572020
TI  - Secretin and pancreatic islet blood flow in anesthetized rats: increased insulin
      secretion with no augmentation of blood perfusion.
AB  - Secretin is a stimulator of both endocrine and exocrine secretions of the
      pancreas, and we aimed to evaluate its effects on splanchnic blood flow in rats
      with a microsphere technique. Anesthetized rats were infused with secretin (0.5
      or 2.0 micrograms/kg body weight/hr) for 10 minutes. Some animals were
      normoglycemic, whereas other received a glucose injection 3 minutes before blood
      flow measurements. Secretin did not affect serum insulin concentrations in
      normoglycemic animals but consistently led to higher insulin concentrations in
      the hyperglycemic rats. Total pancreatic blood flow was increased by the highest
      secretin dose in normoglycemic animals, whereas no effects were seen in the
      hyperglycemic rats. Administration of glucose caused a pronounced increase in
      islet and fractional islet blood flow in saline-infused animals. Secretin
      affected neither islet nor fractional blood flow in normoglycemic or
      hyperglycemic rats. Glucose administration increased duodenal blood flow in
      animals infused with saline and both duodenal and colonic blood flow in rats
      given the lowest dose of secretin. No effects on either colonic or duodenal blood
      perfusion were seen in animals infused with the highest dose of secretin.
      Secretin mainly affects blood flow to the whole pancreas and not that of the
      islets. Furthermore, glucose-induced insulin release can be achieved without a
      simultaneous increase in islet blood flow; that is these two events may be
      dissociated from one another.

PMID- 11572021
TI  - Early imaging of integration response to polypropylene mesh in abdominal wall by
      environmental scanning electron microscopy: comparison of two placement
      techniques and correlation with tensiometric studies.
AB  - The repair of incisional hernias has taken advantage of the strength provided by
      prosthetic mesh grafts, but the best position for inserting the materials has not
      been conclusively established. Environmental scanning electron microscopy (ESEM)
      provides imaging of biologic samples with minimal manipulation. We used ESEM for
      early imaging of the integration response to polypropylene meshes placed in two
      anatomic positions in the abdominal wall and correlated results with tensiometric
      studies. Two macroporous polypropylene prostheses were implanted in a rat model-
      one on the abdominal aponeurotic layer and one on the peritoneal surface--without
      creating a wall defect. Studies were performed over implantation intervals of 7,
      15, and 30 days in strips obtained from the polypropylene fiber-receptor repair
      tissue interface. Microscopic appearance, tensile strength, percent elongation,
      and stiffness were evaluated. Meshes implanted on the abdominal aponeurotic layer
      showed better early tissue incorporation (higher collagen deposition, capillary
      density, cell accumulation) and increased tensile strength, reflecting tighter
      anchorage to the abdominal wall. The percent elongation increased from day 7 to
      day 30 after implantation, mainly in the deep stratum. The ESEM images correlated
      well with biomechanical results, indicating the potential of this technique as a
      powerful, effective tool for use in wound-healing studies.

PMID- 11572022
TI  - Clinical analysis and literature review of massive duodenal diverticular
      bleeding.
AB  - A duodenal diverticulum (DD) appears in 2.5% of upper gastrointestinal (UGI)
      examinations and up to 22% of endoscopic retrograde cholangiopancreaticographies
      (ERCP) and autopsies. Most of these patients are asymptomatic, but the lesion is
      occasionally associated with bleeding, inflammation, perforation, obstruction of
      the duodenum or biliary-pancreatic duct (or both), fistula formation in the bile
      duct, and bezoar formation inside the diverticulum. A total of 816 patients have
      undergone ERCP examination at our institution since January 1987, and 100
      (12.25%) of them have DD. Seven (7%) patients presented with bloody or tarry
      stools from massive UGI bleeding followed by shock. Only two could be diagnosed
      by UGI endoscopy preoperatively. The lesions were demonstrated in angiographic
      studies in another four cases. However, only one was correctly interpreted and
      one required reoperation after a correct repeat endoscopic finding. The lesions
      in the other two patients were identified by thorough exploration during
      laparotomy. The remaining case was diagnosed by intraoperative endoscopy via
      pyloroduodenotomy. Six underwent surgical intervention, and one was successfully
      treated by expectant treatment. Three (50%) had leakage from the duodenotomy but
      recovered uneventfully with conservative treatment. In conclusion, we believe
      that DD bleeding is more frequent than usually thought. A high index of suspicion
      should be raised in cases of UGI bleeding when more obvious and common causes
      have been excluded by routine endoscopy. Aggressive but careful endoscopic
      examination combined with accurate angiography can help us diagnose most of the
      cases preoperatively. Diverticulectomy is an effective surgical procedure, though
      it is associated with a considerable leakage rate. The morbidity is minimal if we
      can identify the lesion earlier and evacuate the lesion without delay.

PMID- 11572023
TI  - Laparoscopic management of bile duct and bowel injury during laparoscopic
      cholecystectomy.
AB  - Accidental injuries to the bile duct and bowel are significant risks of
      laparoscopic surgery and sometimes require conversion to open surgery. Although
      some of the injuries related to laparoscopic cholecystectomy can be managed by
      endoscopic techniques, laparoscopic surgery is not yet sufficiently perfected. We
      investigated the efficacy of laparoscopic management combined with endoscopic
      tube or stent insertion in cases of bile duct and bowel injuries during
      laparoscopic cholecystectomy. Laparoscopic cholecystectomy was attempted on 1,190
      consecutive patients between April 1992 and June 1999. The first 70 patients
      underwent only preoperative intravenous infusion cholangiography (IVC), and the
      remaining 1,120 patients were subjected to both preoperative IVC and
      intraoperative cholangiography. We experienced 16 cases of bile duct injury
      (1.4%). Five patients with circumferential injuries of the bile duct were
      converted to open surgery for biliary reconstruction. The other 11 patients with
      partial laceration injuries of the bile duct and biliary leakage from the cystic
      duct underwent a laparoscopic simple closure technique. In 10 of these patients,
      an endoscopic tube or stent was inserted on the day after surgery to facilitate
      biliary decompression and drainage. Bowel injuries occurred in seven patients
      (0.6%). Three intestinal injuries were due to careless technique, and two
      duodenal injuries and two intestinal injuries were related to dense adhesions.
      All of these injuries were successfully repaired using laparoscopic techniques,
      autosuturing devices, or extracorporeal suturing via the umbilical incision. No
      postoperative complications were identified. We concluded that the biliary injury
      site could be closed with a laparoscopic technique so long as the biliary injury
      was not circumferential. Bowel injuries also could be repaired laparoscopically.

PMID- 11572024
TI  - Hyperamylasemia and subclinical pancreatitis after cardiac surgery.
AB  - Hyperamylasemia after cardiac surgery is common but typically causes no clinical
      concern because it consists mainly of the salivary isoenzyme. In this study we
      evaluated the incidence, source, and time course of postoperative hyperamylasemia
      with special attention to the possibility of subclinical pancreatitis. In 88
      patients prospectively tested for serum amylase and lipase concentrations,
      elastase 1 activity, and amylase isoenzyme characteristics, 57 (64%) showed
      hyperamylasemia during the early postoperative period. In most cases early
      hyperamylasemia was not of pancreatic origin, but two patients were diagnosed
      with subclinical pancreatitis. Among the last 23 patients, 5 of 10 patients with
      early hyperamylasemia exceeding 1000 IU/L showed late hyperamylasemia on the
      seventh postoperative day, when it represented mainly the pancreatic isoenzyme.
      Lipase concentrations and elastase 1 activities were elevated in these cases.
      Late hyperamylasemia following cardiac surgery may be of pancreatic origin and
      indicative of subclinical pancreatitis, even if early hyperamylasemia was of
      salivary origin.

PMID- 11572025
TI  - Histologic factors affecting prognosis following hepatectomy for intrahepatic
      cholangiocarcinoma.
AB  - Long-term survival following hepatectomy for intrahepatic cholangiocarcinoma has
      been poor, and specific factors influencing survival are unclear. In a
      retrospective study we sought to determine prognostic factors related to survival
      in these patients. In 28 patients who underwent hepatic resection for
      intrahepatic cholangiocarcinoma, we investigated the relations of several
      histologic factors to patient survival by univariate and multivariate analyses.
      No deaths occurred during the first 30 days. Median and mean survival times
      following hepatectomy were 409 and 935 days, respectively. The respective
      survival rates at 1, 3, and 5 years were 57%, 27%, and 27%. Resection margin
      status, intrahepatic metastasis, lymph node involvement, and lymphatic invasion
      were significant predictors of outcome. In a multivariate analysis using the Cox
      proportional hazards model, only lymphatic invasion independently predicted
      survival. Curative resection with clear margins was found to prolong survival
      after surgery. Hepatectomy for intrahepatic cholangiocarcinoma without lymphatic
      invasion offers hope for long-term survival.

PMID- 11572026
TI  - Transanal endoscopic microsurgical excision of rectal tumors: indications and
      results.
AB  - Transanal endoscopic microsurgery (TEM) allows local excision of rectal tumors
      located 4 to 18 cm above the anal verge. The technique is not yet generally
      established because of the necessary special instrumentation and tools, the
      unusual technical aspects of the approach, and the stringent patient selection
      criteria. The aim of this prospective, descriptive study was to analyze the
      currently accepted indications for TEM and to evaluate the use of this procedure
      for treating rectal cancer. Over a 4-year period 50 patients aged 31 to 86 years
      (mean 64 years) underwent TEM for treatment of rectal tumors located 12 cm above
      the anal verge (range 4-18 cm). The local complication rate was 4%. Altogether,
      76% of lesions were benign, and 24% were T1 and T2 tumors. Of 12 cancer cases, 4
      required reoperation by total mesorectal resection; the other 8 are currently
      under follow-up management. Over the follow-up period of 30.6 months (range 11-54
      months) the recurrence rate of T1 tumors was 8.3%. TEM is a minimally invasive
      surgical technique that may benefit a small, specific population of patients with
      rectal tumors. Compared with conventional transanal resection, TEM provides
      superior exposure of tumors higher up in the rectum (i.e., up to 18 cm from the
      anal verge). The greater precision of resection combined with low morbidity (10%,
      relative to that of anterior resection) and short duration of hospitalization
      (5.5 days) make this technique a reliable and in some cases more effective
      surgical approach than laparotomy and low anterior resection.

PMID- 11572027
TI  - Colonic J-pouch function at six months versus straight coloanal anastomosis at
      two years: randomized controlled trial.
AB  - The colonic J-pouch (pouch group) functions better than the straight coloanal
      anastomosis (straight group) immediately after ultra-low anterior resection, but
      there are few studies with long-term follow-up. This randomized controlled study
      compared functional outcome, anal manometry, and rectal barostat assessment of
      these two groups over a 2-year period. Forty-two consecutive patients were
      recruited, of which 19 of the straight group [17 men with a mean age of 62.1 +/-
      2.3 (SEM) year] and 16 of the pouch group (11 men with a mean age of 61.3 +/- 3.2
      year) completed the study. Four died from metastases and two emigrated; there was
      no surgical morbidity or local recurrence. At 6 months the Pouch patients had
      significantly less frequent stools (32.9 +/- 2.8 vs. 49 +/- 1.4/week; p < 0.05)
      and less soiling at passing flatus (38% vs. 73.7%; p < 0.05). At 2 years both
      groups had improved with no longer any differences in stool frequency (7.3 +/-
      0.4 vs. 8 +/- 0.2/week) and soiling at passing flatus (38% vs. 53%). Defecation
      problems remained minimal in both groups. Anal squeeze pressures were
      significantly impaired in both groups up to 2 years (p < 0.05). The rectal
      maximum tolerable volume and compliance were not different between groups. Rectal
      sensory testing on the barostat phasic program showed impairment at 6 months and
      recovery at 2 years, suggesting that postoperative recovery of residual afferent
      sympathetic nerves may play a role in functional recovery. In conclusion, stool
      frequency and incontinence were less in the Pouch patients at 6 months; but after
      adaptation at 2 years the straight group patients yielded similar results.
      Nonetheless, this functional advantage can be given to patients with minimal
      added effort or complications by using the colonic J-pouch.

PMID- 11572028
TI  - Evaluation of risk of splenosis during laparoscopic splenectomy in rat model.
AB  - Laparoscopic splenectomy (LS) is an alternative to open surgery. However, there
      is a theoretic risk of splenosis and abdominal cavity dissemination of splenic
      cells if the splenic capsule is broken, as seen by experimental evidence of
      tumoral cell mobilization by the pneumoperitoneum. We evaluated the features of
      splenosis after splenectomy operated via an open approach or under laparoscopic
      control in an experimental model in the rat. A total of 65 Sprague-Dawley rats
      were distributed in seven groups that included the open approach, CO2
      pneumoperitoneum LS, or wall lift LS with or without a splenic graft. Splenic
      function was evaluated 90 day later through (1) scintigraphy with Tc-labeled heat
      damaged erythrocytes; (2) determination of circulating "pitted" cells; and (3)
      analysis of the distribution of splenic pulp in the peritoneal cavity.
      Scintigraphy did not show viable residual tissue in any group after splenectomy;
      splenic activity in the splenic fossa was observed in 40% of the animals with
      grafts. Splenectomy increased the "pit" cell count, but it was reduced to normal
      values with a splenic graft. Necropsy showed normal splenic tissue in the splenic
      fossa in 100% of animals with a graft. Abdominal implants were observed
      significantly more frequent after CO2 LS than after the open surgery or a wall
      lift LS (80% vs. 20% vs. 30%; p < 0.05). In addition, trocar site implants were
      observed with CO2 LS (n = 3) or wall lift LS (n = 2), whereas there were no
      implants in the wound in the open group. We conclude that in an experimental rat
      model the pneumoperitoneum may facilitate abdominal splenosis after LS if the
      splenic capsule is ruptured or if splenic tissue spills compared with surgery
      without gas (open or laparoscopic).

PMID- 11572029
TI  - Hyperparathyroidism in multiple endocrine neoplasia type I: surgical trends and
      results of a 256-patient series from Groupe D'etude des Neoplasies Endocriniennes
      Multiples Study Group.
AB  - The French and Belgian GENEM study group's multiple endocrine neoplasia type I
      (MEN-I) database was used to evaluate trends in clinical presentation, surgical
      treatment of primary hyperparathyroidism (pHPT) (n = 245), and prognostic factors
      for hypercalcemia correction among 256 MEN-I cases. The patients were retrieved
      through the GENEM network from various Belgian and French institutions with the
      help of genetics laboratories. Among the 245 pHPT patients (96%), 42% were men.
      The mean age at the time of diagnosis was 39.5 +/- 13.3 years. Trends were
      studied for three periods: before 1986, from 1986 to 1990, and thereafter. After
      1990 MEN-I patients were more often diagnosed with isolated pHPT (8%, 11%, 28%,
      for the three periods, respectively; p = 0.002); it was seen more often in
      screened patients (31%, 28%, 53%; p = 0.001), more often among those in already
      known MEN-I families (64%, 45%, 72%; p = 0.005), and among those with lower
      preoperative calcemia (2.93, 2.87, 2.79 mmol/L; p = 0.001). The age at pHPT
      diagnosis remained constant throughout the study. The percentage of cervical
      explorations dropped during the entire study (87%, 87%, 53%; p < 0.0001). After
      1985 the percentage of subtotal parathyroidectomies increased (25%, 59%, 51%; p =
      0.0004). Pathology disclosed more hyperplasias (59%, 85%, 74%; p = 0.008).
      Postoperative hypercalcemia decreased (47%, 15%, 19%; p < 0.0001); and
      postoperative hypocalcemia increased nonsignificantly (5%, 15%, 15%; p = 0.1).
      Subtotal parathyroidectomy [odds ratio (OR) 13], no MEN-I family background (OR
      3), and the most recent study period (> 1985) (OR 3) were significant predictive
      factors of hypercalcemia correction according to the multivariate analysis. This
      is the first multicentric study on the management of MEN-I-related pHPT.
      Immediate postoperative hHPT cure increased, but only 80% of the operated
      patients were cured after 1990. Fifteen percent were hypocalcemic. Because MEN-I
      related hHPT cure remains difficult to achieve, we advocate that subtotal
      parathyroidectomies be performed in specialized centers.

PMID- 11572031
TI  - Surgical management of pectus carinatum: 30 years' experience.
AB  - Pectus carinatum is an uncommon malformation that is often more symptomatic than
      the appearance suggests, and one that physicians often do not refer for surgical
      correction. Hospital records of 90 patients who underwent repair of pectus
      carinatum deformities between 1970 and 2000 were reviewed. During the same period
      another 445 patients underwent repair of excavatum deformities. Minimal deformity
      was observed before the age of 10 years for 81 of 90 patients; only 7 of the 90
      underwent repair before age 11 years. All patients were symptomatic; 84 had
      exertional dyspnea and exercise limitation, 52 had frequent respiratory
      infections, 24 had asthma, and 38 had chest discomfort. The mean pectus severity
      score (width of chest divided by the distance between the sternum and spine) was
      1.73 (the normal chest is 2.56). The type of repair varied with the type of
      deformity, consisting of subperiosteal resection of the deformed cartilages,
      transverse osteotomy of the anterior sternum with insertion of a cartilage wedge,
      and support with a steel strut for 4 to 6 months in 76 of 90. There were no
      deaths within 1 year after the repair. Complications included hypertrophic scar
      (n = 13), wound seroma (n = 5), pleural effusion (n = 3), and pneumothorax (n =
      2). The mean blood loss was 78 ml, and the mean hospital stay was 2.6 days. With
      a mean follow-up of 12.8 years, all patients experienced alleviation of
      respiratory symptoms and chest discomfort and diminished exercise limitation; 88
      of 90 patients experienced a very good to excellent long-term result. One patient
      required reoperation. Pectus carinatum often causes more severe respiratory
      symptoms and exercise limitation than is generally recognized. Repair in 90
      patients with carinatum deformities has resulted in marked clinical improvement
      in all patients, with low morbidity and short hospitalization.

PMID- 11572030
TI  - Adrenocortical carcinomas: surgical trends and results of a 253-patient series
      from the French Association of Endocrine Surgeons study group.
AB  - Because of the rarity of adrenocortical carcinoma, survival rates and the
      prognosis for patients who have undergone operation are not well known. The
      purpose of the French Association of Endocrine Surgery was to evaluate these
      factors over an 18-year period. A trend study was associated to assess changes in
      the clinical and biochemical presentations as well as the surgical evolution. A
      total of 253 patients (158 women, 95 men) with a mean age of 47 years were
      included. Cushing syndrome was the main clinical presentation (30%), and hormonal
      studies revealed secreting tumors in 66% of the cases. Altogether, 72% (n = 182)
      of patients underwent resection for cure, and 41.5% (n = 105) of them had an
      extensive resection because of metastatic cancer. A lymphadenectomy was performed
      in 32.5% (n = 89) of the cases. The operative mortality was 5.5% (n = 14).
      Patients were given mitotane as adjuvant therapy in 53.8% of the cases (n = 135).
      The results of staging were stage I in 16 patients (6.3%), stage II (local
      disease) in 126 patients (49.8%), stage III (locoregional disease) in 57 patients
      (22.5%), and stage IV (metastases) in 54 patients (21.3%). Neither tumor staging
      nor the rate of curative surgery changed during the study period. More subcostal
      incisions were performed, and the use of mitotane increased significantly. The 5
      year actuarial survival rates were 38% overall, 50% in the curative group, 66%
      for stage I, 58% for stage II, 24% for stage III, and 0% for stage IV.
      Multivariate analysis showed that mitotane benefited only the group of patients
      not operated on for cure. A better prognosis was found in patients operated on
      after 1988 (p = 0.04), in those with precursor-secreting tumors (p = 0.005), and
      in those at local stages of the disease (p = 0.0003). Thus mitotane benefited
      only patients not operated on for cure. Curative resection, precursor secretion,
      recent diagnosis, and local stage were favorably associated with survival.

PMID- 11572032
TI  - Adrenal incidentaloma.
AB  - Because of the frequent use of computed tomography and other abdominal imaging
      modalities, clinicians more frequently see the incidentally discovered,
      clinically silent adrenal mass. Most adrenal incidentalomas should be evaluated
      for hormonal activity and assessed for their risk of malignancy. Adrenalectomy is
      indicated for hyperfunctioning tumors and for any potential primary malignant
      adrenal lesion. Nonfunctioning cortical adenomas < 4 to 5 cm in size should be
      followed clinically and radiographically. Laparoscopic adrenalectomy has been
      used increasingly as the preferred approach in patients who require surgical
      resection whereas open adrenalectomy is reserved for patients with large,
      malignant tumors. The indications for adrenalectomy in patients with
      nonfunctioning adrenal tumors should not be liberalized because of the
      laparoscopic approach.

PMID- 11572033
TI  - Adrenal cortical carcinoma.
AB  - Adrenal cortical carcinoma is a rare endocrine tumor for which complete surgical
      resection is the only potentially curative treatment. Accurate preoperative
      evaluation (biochemical and radiographic) of the patient who presents with an
      adrenal mass maximizes the opportunity for the patient to undergo a complete,
      margin-negative resection of the primary tumor, which is the most powerful
      prognostic variable for long-term survival. The response to chemotherapy or
      mitotane is modest in patients with advanced disease. Hopefully, an improved
      understanding of the molecular pathogenesis of this challenging tumor will lead
      to the development of more effective therapies in the future.

PMID- 11572035
TI  - Cushing syndrome due to ectopic adrenocorticotropic hormone secretion.
AB  - Cushing syndrome (CS) caused by ectopic adrenocorticotropic hormone (ACTH)
      production (EA) poses major challenges diagnostically by mimicking the pituitary
      dependent form of CS and therapeutically by producing severe, life-threatening
      hypercortisolemia. This retrospective follow-up study describes the clinical
      characteristics and course of EA in a large referral center. Computer-based cross
      index codes for EA, CS, and bilateral adrenalectomy were used to identify
      patients treated at the Mayo Clinic between 1956 and 1998. EA was confirmed in
      106 patients. Gender distribution showed a slight female predominance (61:45).
      Bronchial carcinoid was the most frequent cause of EA (25%), followed by islet
      cell cancer (16%), small-cell lung carcinoma (11%), medullary thyroid cancer
      (8%), disseminated neuroendocrine tumor of unknown primary source (7%), thymic
      carcinoid (5%), pheochromocytoma (3%), disseminated gastrointestinal carcinoid
      (1%), and other tumors (8%). No tumor was found in 16% of patients. Altogether,
      28 patients were managed medically, and the others underwent curative tumor
      resection (13 patients) or bilateral adrenalectomy (65 patients). Surgically
      treated patients had longer survival, but this was most likely affected by
      treatment bias. The diagnoses of CS and ACTH-secreting neoplasm were usually
      concurrent, although, there were remarkable cases in which the two conditions
      were diagnosed several years apart. Curative resection of the tumor producing EA
      was possible in a small proportion of patients (12%). When curative resection is
      not possible, patients who are reasonable surgical candidates are likely to
      benefit from adrenalectomy. Additional experience with bilateral laparoscopic
      adrenalectomy should increase the number of patients who benefit from adrenal
      directed surgery.

PMID- 11572034
TI  - Cytotoxic treatment of adrenocortical carcinoma.
AB  - Adrenocortical carcinoma (ACC) is a rare, aggressive tumor that is often detected
      in an advanced stage. Medical treatment with the adrenotoxic drug mitotane has
      been used for decades, but critical prospective trials on its role in residual
      disease or as an adjuvant agent after surgical resection are still lacking. The
      concept of a critical threshold plasma level of the drug must be confirmed in
      controlled studies. Because individual responsiveness cannot be predicted, the
      use mitotane is still advised for nonresectable disease. In case of cortisol or
      other steroid overproduction, several drugs (e.g., ketoconazole or
      aminoglutethimide) may be used. Chemotherapy with single agents (e.g.,
      doxorubicin or cisplatin) have been disappointing, with low response rates (<
      30%) and a short response duration. Part of this refractoriness may be explained
      by the fact that ACC tumors express the multidrug-resistance gene MDR-1.
      Chemotherapy with multiple agents has been tested in smaller series and has
      resulted in significant side effects. The best results were achieved by the
      combination of etoposide, doxorubicin, and cisplatin associated with mitotane,
      achieving a response rate of 54%, including individual complete responses. To be
      able to make progress in treating advanced ACC disease, adjuvant multicenter
      trials must be encouraged. When mitotane-based therapies are used, monitored drug
      levels are mandatory.

PMID- 11572036
TI  - Primary aldosteronism: are we diagnosing and operating on too few patients?
AB  - Many cases of potentially curable primary aldosteronism are currently likely to
      be diagnosed as essential hypertension unless screening tests based on
      suppression of renin are carried out in all hypertensive patients. More than half
      of the patients with primary aldosteronism detected in this way have normal
      circulating potassium levels, so measurement of potassium is not enough to
      exclude primary aldosteronism. When primary aldosteronism is diagnosed, fewer
      than one-third of patients are suitable for surgery as initial treatment, but
      this still represents a significant percentage of hypertensive patients. After
      excluding glucocorticoid-suppressible primary aldosteronism, adrenal venous
      sampling is essential to detect unilateral production of aldosterone and diagnose
      angiotensin-responsive aldosterone-producing adenoma. One cannot rely on the
      computed tomography scan. If all hypertensive patients are screened for primary
      aldosteronism and the workup is continued methodically in those with a positive
      screening test, patients with unilateral overproduction of aldosterone who
      potentially can be cured surgically are not denied the possibility of cure.

PMID- 11572037
TI  - Genetic background of adrenocortical tumor development.
AB  - The increasing occurrence of incidentally discovered benign adrenocortical tumors
      has become a clinical dilemma because of the difficulties in differentiating them
      from their malignant counterpart. Adrenocortical tumors are associated with
      familial cancer syndromes such as the Beckwith-Wiedemann syndrome, the Li
      Fraumeni syndrome, the Carney complex, multiple endocrine neoplasia type 1,
      congenital adrenal hyperplasia, and the McCune-Albright syndrome. Genetic events
      are known to take place on the chromosomal and gene level in sporadic
      adrenocortical tumors.

PMID- 11572038
TI  - In vitro release of aldosterone and cortisol in human adrenal adenomas correlates
      to mRNA expression of steroidogenic enzymes for genes CYP11B2 and CYP17.
AB  - Adenomas of the adrenal cortex cause different disorders depending on the main
      steroid synthesized and released. The aim of this research is to increase our
      understanding of the pathophysiology of steroidogenesis in adrenocortical
      disorders by comparing the release of steroids from adrenocortical adenomas in
      vitro with the messenger RNA (mRNA) expression of steroid synthesizing enzymes.
      Fourteen patients with adrenal tumors were included in the present study; nine
      were diagnosed with primary aldosteronism and three with Cushing's syndrome. Two
      patients had an adrenal tumor discovered on computed tomography (CT) during
      workup for an unrelated disease. Serum cortisol, plasma aldosterone, and urinary
      catecholamines were normal. Tissue was taken for in vitro steroid release, and
      aldosterone and cortisol in the medium after a 1-hour incubation were determined.
      Oligonucleotide probes with sequences complementary to mRNAs encoding for the
      steroid synthesizing enzymes 11 beta-hydroxylase (CYP11B1), 18-hydroxylase
      (CYP11B2), 17 alpha-hydroxylase (CYP17), and 21-hydroxylase (CYP21) were
      synthesized (Genset, Paris, France) and in situ hybridization was performed.
      Moderate expression of CYP11B2 and low expression of CYP11B1 were seen in the
      zona glomerulosa. The zona fasciculata of the control adrenals expressed a high
      signal of CYP11B1, whereas the expression of CYP11B2 was very low. There was
      considerable variation in aldosterone release from the aldosteronomas, whereas
      the tumors from the Cushing patients showed no detectable release of aldosterone.
      In contrast, tumors from patients with primary aldosteronism, Cushing's syndrome,
      and no hyperfunction all had the ability to synthesize and release cortisol in
      vitro. The highest cortisol release was found in tumors from patients with
      Cushing's syndrome, but also the nonhyperfunctioning tumors and some of the
      aldosteronomas released significant amounts of cortisol. The two patients with
      highest release of aldosterone in vitro showed the highest expression of CYP11B2
      and the lowest expression of CYP11B1 and CYP17. The remaining aldosteronomas had
      low expression of CYP11B2, similar to the two other groups. Expression of CYP11B1
      was high as expected in the Cushing adenomas, but also the two
      nonhyperfunctioning tumors and some of the aldosteronomas showed a moderate
      expression. Adenomas from Cushing's syndrome, nonhyperfunctioning adenomas, and
      some of the aldosterone-producing adenomas had moderate to high expression of
      CYP17. This paper presents new means for functional characterization of
      adrenocortical tumors. Diagnosis of an aldosteronoma is often difficult, and with
      the advent of these methods it is possible to determine the functional capacity
      of a tumor, once it is removed. This is of special interest if the patient
      remains hypertensive postoperatively, and it is not clear whether the patient
      indeed had a functioning tumor.

PMID- 11572039
TI  - History of endoscopic and laparoscopic surgery.

PMID- 11572040
TI  - "Surgeon's approach to the thyroid gland: surgical anatomy and the importance of
      technique.".

PMID- 11572041
TI  - "Surgeon's approach to the thyroid gland: surgical anatomy and the importance of
      technique.".

PMID- 11572042
TI  - [Etiological epidemiological schizophrenia research].

PMID- 11572043
TI  - [Why is the risk of schizophrenia greater in cities than in the country?].
AB  - Schizophrenia is a serious and relatively common mental illness. Its causes are
      not known in detail, but both genetic and environmental factors are assumed to
      contribute to the risk of schizophrenia. A number of studies find that the
      prevalence and incidence are higher in individuals born or raised in city areas
      than in individuals from rural areas. The causes of this difference are unknown.
      This paper reviews possible methodological problems as an explanation of these
      differences and discusses possible candidate risk factors that could underlie
      urban-rural differences. It is concluded that the causes of urban-rural
      differences in the risk of schizophrenia are unknown, but that cumulative or
      repeated exposure during upbringing to factors more common in cities, for
      instance exposure to pollutants like lead, are hypothetically possible
      explanations of the urban-rural difference.

PMID- 11572044
TI  - [Molecular biology in acute lymphoblastic leukemia].

PMID- 11572045
TI  - [Fever after travel. Status and perspective].

PMID- 11572046
TI  - [Fractures of the sternum].
AB  - Sternal fractures almost solely occurs as a result of traffic accidents and are
      considered a marker of more serious injury, especially damage to the myocardium.
      Patients with an isolated sternal fracture are therefore often admitted to
      hospital for cardiac monitoring. In drivers and passengers restrained by safety
      belts sternal fracture is a benign injury: the complication rate is low and
      healing is usually uneventful. Routine admission and monitoring of patients with
      isolated sternal fracture is not indicated when the electrocardiogram and chest X
      ray, apart from the fracture, are normal. A subgroup of patients at increased
      risk of cardiac arrhythmias is defined. These patients should be admitted for
      observation.

PMID- 11572047
TI  - [Malaria. An evaluation of 127 patients treated in Rigshospitalet in 1999 and
      2000].
AB  - INTRODUCTION: The incidence of malaria has increased globally to 500 million
      cases a year. Imported malaria in travellers comprises only a small fraction, but
      the disease has become a serious problem in Europe and the United States. The aim
      of the present study was to elucidate the epidemiological and clinical aspects of
      patients with imported malaria in Denmark. MATERIAL AND METHODS: All patients
      treated for malaria at the Department of Infectious Diseases, Rigshospitalet, in
      1999-2000 were evaluated retrospectively. Age, sex, nationality, destination,
      chemoprophylaxis, symptoms, duration of symptoms, parasitaemia, treatment, and
      complications were registered. RESULTS: Seventy per cent of the patients had
      falciparum malaria. Of these, 95% had been infected in Africa and 46% of these
      patients were Africans living in Denmark. Only 50% of all patients had been
      taking chemoprophylaxis and of these only half had been compliant. Chloroquine
      and proguanile were most commonly used. Seven patients had parasitaemia above 5%,
      but only one of these developed complicated malaria. DISCUSSION: The risk of
      complicated malaria in this series was low and seems to be related to lack of
      chemoprophylaxis, advanced age, and duration of symptoms.

PMID- 11572048
TI  - [The effect of dietary oils on blood lipids and the risk of ischemic heart
      disease with special emphasis on olive oil. A literature review].
AB  - INTRODUCTION: The European Union is financing a large-scale campaign, in which
      olive oil is represented as the optimal fat for dietetic prevention of coronary
      heart disease. METHOD: We reviewed all controlled dietary studies comparing the
      effect on blood lipids of olive oil and alternative vegetable oils. Fifteen
      studies were identified. RESULTS: Consumption of olive oil was associated with
      significantly raised plasma concentrations of low density lipoprotein cholesterol
      (+6.5%), high density lipoprotein cholesterol (), and triglycerides (+7%) as
      compared with an average of the alternative oils. In the light of these
      differences in blood lipids and the risk coefficients published earlier, we
      calculated that the consumption of olive oil was associated with a 7% increase in
      the risk of coronary heart disease. CONCLUSION: We conclude that olive oil cannot
      be considered more cardioprotective than other unsaturated vegetable oils as
      judged from its effects on blood lipids.

PMID- 11572049
TI  - [Thrombolytic treatment of acute cerebral infarction].
AB  - INTRODUCTION: Thrombolytic therapy of acute ischaemic stroke within three hours
      of the onset of symptoms is approved by health authorities in the USA and Canada,
      but not in Europe. METHODS: We report seven patients treated with recombinant
      tissue plasminogen activator (rtPA) within three hours of the onset of stroke
      according to an open protocol following internationally accepted guidelines.
      RESULTS: Three patients with initial severe neurological deficits made an almost
      complete recovery within the first 24 hours after treatment. Two patients had a
      partial remission, and two patients had no benefit. There were no bleeding
      complications. DISCUSSION: The present results are in accordance with the
      Cochrane Library's analysis of published data regarding thrombolytic therapy.

PMID- 11572050
TI  - [Sibships characteristics, influenza and risk of schizophrenia. A population
      based cohort study].
AB  - INTRODUCTION: To address the hypothesis that infections, perhaps prenatal
      exposure to influenza virus, might increase the risk of schizophrenia we studied
      the possible association between schizophrenia risk and birth order, sibship
      size, interval between siblings, and influenza prevalence. MATERIAL AND METHODS:
      We established a population-based cohort of 1,746,366 persons born to Danish
      woman who themselves were born since 1935 using data from the Civil Registration
      System. Schizophrenia in cohort members (n = 2669) and their parents was
      identified by linkage with the Danish Psychiatric Case Register. Influenza
      notifications per month in Denmark were obtained from the National Board of
      Health and Statens Serum Institut. RESULTS: We found no association between birth
      order and schizophrenia risk or between schizophrenia risk and influenza
      prevalence during any month of prenatal life. Coming from a large sibship and
      having a short interval to the nearest older or younger sibling was associated
      with an increased risk of schizophrenia. DISCUSSION: Our findings do not add
      support to the hypothesis that schizophrenia is associated with prenatal exposure
      to influenza virus or other common infections, but are compatible with the
      hypothesis that environmental exposure, perhaps to common infections in
      childhood, may be a risk factor.

PMID- 11572051
TI  - [Amniocentesis and chorionic villi biopsy. A 10-year material].
AB  - PURPOSE: The aim of the study was to evaluate the prenatal diagnosis at a
      secondary referral hospital. METHOD: A retrospective study was carried out on
      1752 women examined by amniocentesis (AC) (n = 1037) or chorion villus sampling
      (CVS) (n = 715) at Randers Centralsygehus from 1 April 1987 to 31 December 1996.
      RESULTS: A cytogenetic diagnosis was made in 99.8% of the AC group and 99.4% of
      the CVS group. Complications, recorded as either spontaneous abortion,
      bleeding/threatening abortion, pain/contractions or amniotic fluid leakage, were
      seen in 1.9%, 3.3%, 2.9%, and 2.3% after AC and 1.8%, 7.3%, 3.4%, and 0% after
      CVS. There were significantly more re-examinations after CVS when the procedure
      was carried out by less experienced operators (p < 0.003), whereas experience did
      not influence the number of re-examinations after AC (p = 0.8). CONCLUSION: The
      frequency of complications during prenatal procedures performed over a period of
      ten years was comparable with that reported in other studies. It is expedient and
      safe to perform prenatal examinations at a secondary referral hospital where
      currently 200 procedures are performed each year.

PMID- 11572052
TI  - [Biloma].
AB  - Most cases of biloma are caused by liver trauma or surgical intervention.
      However, spontaneous cases have been reported. We present a patient with
      spontaneous biloma which may have developed secondary to stenosis of the common
      bile duct or infarction of the liver. The initial treatment was percutaneous
      drainage, followed by ERCP with papillotomy and stenting of the common bile duct.
      Despite this therapy symptoms recurred and the patient had to undergo resection
      of a liver segment. The treatment of biloma in general is discussed.

PMID- 11572053
TI  - [Enteritis cystica profunda in a patient with Crohn disease].
AB  - We describe a case report of a 58-year-old woman presenting with acute intestinal
      obstruction in association with Crohn's disease. The terminal ileum was resected
      and was found to be heavily thickened and stenotic, with multiple, mucinous cysts
      in the bowel wall. Pathological findings were otherwise consistent with Crohn's
      disease. Enteritis cystica profunda was diagnosed. Diagnosis and differential
      diagnoses (mucin producing adenocarcinoma and pneumatosis cystoides intestinalis)
      are discussed.

PMID- 11572054
TI  - [Picture of the month: Ulcerations in the esophagus].

PMID- 11572055
TI  - [Home blood pressure measurement. Is it reliable enough?].

PMID- 11572056
TI  - [New target-aimed molecular cancer treatment of chronic myeloid leukemia and
      gastrointestinal stromal tumor].

PMID- 11572057
TI  - [The enclosed notes with too much information].

PMID- 11572058
TI  - ["Common trunk"].

PMID- 11572059
TI  - [Why is there no total control of the treatment of lung cancer in Denmark?].

PMID- 11572060
TI  - [Ogilvie syndrome].

PMID- 11572061
TI  - [Acute colonic pseudo-obstruction].

PMID- 11572062
TI  - GHC's goal: hanging on to gains in evidence-based care.

PMID- 11572063
TI  - Colonoscopy benchmarks suggest less invasive tack not always most productive.
AB  - A new study of colonoscopy calls into question the conventional wisdom about its
      use versus that of sigmoidoscopy, and provides a host of crucial benchmarks for
      the nation's second most commonly performed outpatient procedure.

PMID- 11572064
TI  - Survey results hint at trend toward incentives based on quality, safety.

PMID- 11572065
TI  - Minnesota plans and providers try collaboration to boost quality.
AB  - What could possibly entice health plans and providers to agree on a common set of
      evidence-based protocols? Plans and providers in this groundbreaking Minnesota
      initiative explain how they work together to provide consistent care to more than
      95% of the state's covered lives.

PMID- 11572066
TI  - Use these simple formats to develop financial profiles.
AB  - For both independent and hospital-owned physician practices, determining the cost
      of care is crucial when negotiating managed care contracts. A practice in North
      Carolina offers a detailed but straightforward way to do just that with
      information and software you probably already have.

PMID- 11572067
TI  - Use of epoetin for anemia in chronic renal failure.

PMID- 11572068
TI  - [Reciprocity regulation in photobiology. An overview].
AB  - According to the rule of Bunsen and Roscoe, a photochemical reaction is directly
      proportional to the total energy dose, irrespective of the time over which this
      dose is delivered. To date few studies have addressed the validity of this rule
      in experimental and applied photobiology. Most of these data point to the fact
      that the rule of reciprocity is invalid or of limited validity for many
      photobiological reactions. For UV-induced cell death, photocarcinogenesis,
      psoralen photochemistry, and the effects of low level laser radiation it has been
      shown that at a constant total dose, the intensity of the source is a major
      factor that determines quality and quantity of the response. In clinical
      photomedicine systematic investigations on the reciprocity of exposure time and
      radiation intensity are lacking. Such studies are urgently needed since it can be
      concluded from experimental evidence, that their results might lead to
      therapeutic regimens with an improved therapeutic index, i.e. maximized
      therapeutic efficacy with minimized adverse reactions.

PMID- 11572069
TI  - [Consensus recommendations for quality assurance in inpatient dermatological
      rehabilitation].

PMID- 11572070
TI  - [Cyclic neutropenia. Detection of a mutation in the gene for neutrophil elastase
      (ELA2)].
AB  - BACKGROUND AND OBJECTIVE: Cyclic neutropenia is a rare congenital hematopoietic
      disease which occurs sporadically or as an autosomal dominantly inherited
      disorder. Recently, the locus for cyclic neutropenia was mapped to chromosome
      19p13.3. Autosomal dominant and sporadic cyclic neutropenia are now attributable
      to mutations of the ELA2 gene encoding neutrophil elastase. PATIENTS/METHODS:
      Based on a case report we review the clinical picture and diagnostic criteria of
      cyclic neutropenia and report about the recent molecular biological findings and
      current treatment options. RESULTS: Serial blood cell counts revealed the
      characteristic oscillations of the circulating neutrophils with 21-day
      periodicity from near normal to extremely low levels. The neutrophil nadir lasted
      3-5 days. The neutropenia was associated with fever, malaise, painful oral
      aphthous ulcers and lymphadenopathy. Mutational analysis of the patient's genomic
      DNA revealed a single base-pair transition (nt 4716, G-->A) in intron 4 of ELA2.
      Since the initiation of therapy with subcutaneous recombinant human granulocyte
      stimulating colony factor (rHuG-CSF) 24 months ago, the patient has been free of
      symptoms. CONCLUSIONS: Despite the typical medical history with onset of the
      symptoms in early infancy the diagnosis of cyclic neutropenia was not established
      until the age of 9 years. A common reason for the delayed diagnosis of cyclic
      neutropenia may be unawareness of the rare but distinctive disorder and the
      practice of obtaining screening blood counts without leukocyte differentials.
      Patients with cyclic neutropenia should be enrolled to the Severe Chronic
      Neutropenia International Registry (SCNIR).

PMID- 11572071
TI  - [Stripping operations of the parva and magna saphenous veins. Long-term study in
      relation to pre- and postoperative dysfunction].
AB  - BACKGROUND AND OBJECTIVE: Little data is available on the log-term effects of
      stripping the greater and lesser saphenous veins in combination with pre- and
      post-operative function tests. The goal of this study was to record the long-term
      course after surgery based on the function data. PATIENTS/METHODS: Drain-off
      capability was measured preoperatively and postoperatively by light reflection
      rheography in 203 patients (58 men, 145 women) between 17 and 79 years.
      Questionnaires were used about 9 years after surgery to determine the nature of
      the post-operative complaints. RESULTS: Nine years after surgery 58% of the
      patients still had no discomfort, and 78% had fewer problems with venous ulcers.
      About 60% reported improvement of swelling and skin changes. The results tended
      to be better in men. Freedom of complaints was longer-lasting where venous
      drainage had been good before surgery. CONCLUSIONS: Stripping operations can
      produce long-lasting improvement of venous ulceration and the above-mentioned
      complaints in a high percentage of patients.

PMID- 11572072
TI  - [Nevus of Ota and choroid melanoma].
AB  - A 59-year-old patient presented with metastatic uveal melanoma that developed in
      a nevus of Ota. The nevus of Ota or oculodermal melanocytosis contains an
      increased number of dermal melanocytes in the distribution of the ophthalmic and
      maxillary divisions of the trigeminal nerve. Malignant transformation arising in
      a nevus of Ota may occur in all anatomical sites influenced by the nevus. Most
      often the choroid is involved. Although the nevus of Ota is rare in Caucasians,
      associated melanoma is more common than in Asians or black people. The
      dermatologist should be aware of this problem and aim at an interdisciplinary
      management of these patients.

PMID- 11572073
TI  - [Atypical herpes simplex virus type 2 manifestations on the hand].
AB  - Cutaneous and mucocutaneous herpes simplex virus (HSV) type 1 and type 2
      infections are some of the most common virus infections of man. Despite optimal
      laboratory diagnosis and widely improved antiviral therapy, only 20 percent of
      patients suffering from genital herpes are correctly diagnosed, and even less
      often is appropriate therapy prescribed. Atypical herpes includes vegetating
      forms in atypical locations, mild cases and even asymptomatic herpes. Such
      atypical cases often remain undetected and do not receive specific and sufficient
      treatment. Two case reports illustrate the importance of clinically diagnosing
      herpes with atypical manifestations in immunodeficient patients.

PMID- 11572074
TI  - [Large melanocytic nevi in generalized atrophic benign epidermolysis bullosa
      (epidermolysis bullosa nevi)].
AB  - Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal form of
      junctional epidermolysis bullosa. The expression of type XVII collagen (180 kDa
      bullous pemphigoid antigen) or of laminin 5 is markedly reduced in the skin. A 13
      year-old patient with GABEB, developed several large, asymmetric, irregularly
      pigmented melanocytic nevi with poorly defined borders. They had appeared
      following blister formation since 8 years of age. Histological examination
      revealed an irregular proliferation of monomorphous melanocytes at the
      dermoepidermal junction. Small nests of melanocytes were focally present. This
      case further emphasizes the difficulty in differentiating nevi appearing in GABEB
      from malignant melanoma.

PMID- 11572075
TI  - [Bilateral, asymmetric herpes zoster (herpes zoster duplex asymmetricus)].
AB  - A 73-year-old female patient presented with asymmetric herpes zoster. She was
      treated successfully with systemic immunostimulants, vitamin B1 tablets and
      topical etheric acetyl-salicylic acid solution. No underlying malignancy,
      immunodeficiency or other systemic diseases could be detected.

PMID- 11572076
TI  - [Recurrent chancriform mucous membrane ulcer in plasmacytoma with secondary IgA
      deficiency. Pyoderma chancriforme of the tongue].
AB  - A 66 year old patient presented with a nine month history of recurrent oral
      ulcerations involving the tongue. We diagnosed chancriform pyoderma and a
      previously not identified multiple myeloma with secondary immunoglobulin
      deficiency. Clinically and histologically we excluded a necrotizing ulcerative
      stomatitis as found in individuals with cellular immunodeficiency as in late
      stage HIV-infection. On culture only Neisseria catarrhalis was found. Chancriform
      pyoderma is often associated with local bacterial infections, especially
      Staphylococcus aureus. The most common sites are the genitalia and periorbital
      region; involvement of the oral mucosa is uncommon. To the best of our knowledge,
      this is the fourth reported case with tongue lesions. The multiple myeloma
      associated immunoglobulin deficiency might have facilitated the oral
      manifestations of chancriform pyoderma.

PMID- 11572077
TI  - [Multiple fibrofolliculomas].
AB  - Fibrofolliculoma is a rare tumor of the perifollicular mesenchyma. A 44-year old
      man noticed a growing number of small whitish firm papules on his neck and the
      upper thorax over the past two years. Histological examination demonstrated on
      multiple biopsies typical features of fibrofolliculoma. Further evaluation of the
      patient has not revealed any sign of neoplasia. The variable clinical
      manifestations of fibrofolliculomas are discussed.

PMID- 11572078
TI  - [Transverse nasal groove. A rare embryological error in nature].
AB  - Two patients presented with a transverse groove located between the lower third
      and upper two-thirds of the nose since birth. The alar and triangular cartilage
      attach themselves in a linear transverse fashion, the so called nasal line. It is
      important to recognize the nasal line as a localizing factor for milia, cysts and
      comedones. The nasal line is rather easily overlooked but awareness of its
      existence allows one to quickly confirm that it is not a rarity. We propose an
      embryological origin.

PMID- 11572079
TI  - [Large surface yellowish plaque in the area of burn scars].

PMID- 11572080
TI  - [Human papillomaviruses and their role in carcinogenesis].

PMID- 11572081
TI  - [Comment on the contribution by P. Gottlober et al.: "Allergic contact dermatitis
      in beauty shop customers"].

PMID- 11572082
TI  - Function and interactions of integrins.
AB  - Integrins are heterodimeric cell adhesion molecules that link the extracellular
      matrix to the cytoskeleton. The integrin family in man comprises 24 members,
      which are the result of different combinations of 1 of 18 alpha- and 1 of 8 beta
      subunits. Alternative splicing of mRNA of some alpha- and beta-subunits and
      postranslational modifications of integrin subunits further increase the
      diversity of the integrin family. In their capacity as adhesion receptors that
      organize the cytoskeleton, integrins play an important role in controlling
      various steps in the signaling pathways that regulate processes as diverse as
      proliferation, differentiation, apoptosis, and cell migration. The intracellular
      signals that lead to these effects may be transduced via cytoplasmic components,
      which have been identified as integrin-binding proteins in yeast two-hybrid
      screens and which could mediate the coupling of integrins to intracellular
      signaling pathways. In this review an overview is given of the function and
      ligand-binding properties of integrins as well as of proteins that associate with
      integrins and may play a role in their signaling function.

PMID- 11572083
TI  - Zonal distribution of Purkinje cells in the zebrafish cerebellum: analysis by
      means of a specific monoclonal antibody.
AB  - We have isolated a monoclonal antibody that recognizes a 42-kDa protein from
      adult zebrafish brain. The antibody stains the typical drop-shaped perikaryon of
      Purkinje cells and their dendrites. The cerebellum of teleosts has complex
      features. It is composed of three parts; the valvula cerebelli (Va), the corpus
      cerebelli (CCe), and the crista cerebellaris (CC). In higher vertebrates, the
      molecular layer is always found as the most outer layer of the cerebellum, but in
      teleosts, some of the granular cells are located on the surface of the Va. In
      higher vertebrates, the boundary between the granular and molecular layers always
      contains Purkinje cells, but this does not occur in teleosts. The Purkinje cells
      are found only in a part of the boundary in Va. We have found that the layer
      containing Purkinje cells forms a continuous zone in the cerebellum in the
      zebrafish. The complex structure of the cerebellum is more easily understood with
      the aid of the concept of a "Purkinje zone". The Purkinje zone starts at the
      caudal end of Val (lateral division of Va), turns at the edge of Va toward Vam
      (medial division of Va), connects to CCe, and ends at the bottom of CCe. The
      dendrites are found only on one side of the zone. The dendrites of the Purkinje
      cells in Vam are planar and are packed regularly, similar to those of higher
      vertebrates. However, the dendrites in Val and the posterior part of CCe are not
      planar and are irregularly packed.

PMID- 11572084
TI  - Localization of endothelin-A and -B receptors during the postnatal development of
      rat cerebellum.
AB  - Intense expression of mRNA of endothelin-B receptor (ETBR) has been detected in
      the Bergmann glia of cerebellum by in situ hybridization, but the intracellular
      localization has not been reported because of the absence of a useful antibody
      for immunohistochemical investigations. We made polyclonal antibodies against the
      carboxyl terminus of human ETBR (420-442) and ETAR (403-427), and performed light
      and electron-microscopic immunohistochemistry of the wild-type and ETBR
      deficient (sl/sl) rat cerebella. Localization of ETBR during postnatal
      development was examined by double-staining immunofluorescence using antibodies
      against ETBR and S-100 beta. In the wild-type rats, ETBR immunoreactivity
      appeared from postnatal day 5 (P5) and was distributed diffusely in the processes
      and cell bodies of S-100 beta-positive glial cells. By P14, ETBR immunoreactivity
      was concentrated in the Golgi apparatus of Bergmann glial cell soma and the
      plasma membrane of its processes. The ETBR-positive astrocytes in the granular
      layer decreased in number during P7-14 and had disappeared by week 3. At 3 weeks,
      ETBR immunoreactivity was restricted to the Golgi apparatus of Bergmann glia. In
      the sl/sl rats, ETBR immunoreactivity was not observed at all. In contrast to
      ETBR, ETAR immunoreactivity appeared transiently in the cytoplasm of all
      astrocytes (Bergmann glia and astrocytes in the granular layer) in the 9- to 14
      day-old wild rats and 7- to 14-day-old sl/sl rats, and disappeared within 3 weeks
      in both. Granule cells did not express immunoreactivity for ETBR and ETAR from
      the neonatal stage to adulthood. Changes in the intracellular localization of
      ETBR and transient expression of ETAR may be correlated with the changes of glial
      functions and proliferation during postnatal development of rat cerebellum.

PMID- 11572085
TI  - Projections of excitatory and inhibitory motor neurones to the circular and
      longitudinal muscle of the guinea pig colon.
AB  - The aim of this study was to identify myenteric pathways to the circular and
      longitudinal muscle of the guinea pig proximal colon. To identify excitatory and
      inhibitory muscle motoneurones, we applied the neuronal retrograde tracer DiI
      onto the circular or longitudinal muscle layer and performed additional
      immunohistochemistry for nitric oxide synthase (NOS) and choline
      acetyltransferase (ChAT). On average 166 +/- 81 circular muscle motoneurones
      (CMMN) and 100 +/- 74 longitudinal muscle motoneurones (LMMN) were labelled by
      DiI tracing. Myenteric pathways innervating the muscle were either ascending (DiI
      labelled neurones with oral projections) or descending (DiI-labelled neurones
      with anal projections). The circular muscle was preferentially innervated by
      ascending pathways (66.0 +/- 9.1%). Most ascending CMMN were ChAT-positive (87.2
      +/- 8.5%), whereas descending CMMN were mainly NOS-positive (82.3 +/- 14.6%).
      Most ascending (62.2 +/- 11.1%) and descending (82.0 +/- 12.5%) CMMN had
      circumferential projection preferences (circumferential projections were longer
      than projections along the longitudinal gut axis). In contrast to the polarised
      projections to the circular muscle, the longitudinal muscle was equally
      innervated by ascending (46.2 +/- 15.1%) and descending (53.9 +/- 15.1%)
      neurones. Ascending and descending pathways to the longitudinal muscle consisted
      predominantly of ChAT-positive neurones (98.1 +/- 1.9% and 68.0 +/- 8.5%,
      respectively), and both pathways had prominent longitudinal projection
      preferences. Only 25.5% of the descending LMMN were NOS-positive. In conclusion,
      the circular muscle in the proximal colon is innervated by descending inhibitory
      (NOS-positive neurones) and ascending excitatory (ChAT-positive neurones)
      pathways. In contrast, the longitudinal muscle is primarily innervated by
      ascending and descending excitatory motoneurones, and only a small proportion of
      the descending pathway consisted of inhibitory motoneurones.

PMID- 11572086
TI  - Pivotal role of the interstitial cells of Cajal in the nitric oxide signaling
      pathway of rat small intestine. Morphological evidence.
AB  - The nitric oxide (NO) signaling pathway is a major nonadrenergic-noncholinergic
      transmitter mechanism in the enteric nervous system. Our aim was to localize the
      enzymes in question, i.e., neuronal nitric oxide synthase (nNOS), soluble
      guanylate cyclase (sGC), and cGMP-dependent kinase type I (cGK-I) in rat small
      intestine by indirect immunofluorescence. nNOS staining was found in neurons of
      the myenteric plexus and in varicose nerve fibers mainly in the circular muscle
      layer. The cells positive for neurokinin-1 (NK-1) receptor and c-kit
      (interstitial cells of Cajal, ICC) in the deep muscular plexus (DMP) did not show
      nNOS reactivity, but nNOS-positive nerve fibers were directly adjacent to them.
      sGC was found in flattened cells surrounding myenteric ganglia (periganglionic
      cells, PGC), in ICC of the DMP, faintly in smooth muscle cells (SMC), and in
      cells perivascularly scattered throughout the circular muscle layer. cGK-I
      immunoreactivity was found abundantly in PGC (which presumably are ICC), in ICC
      of DMP, in SMC of the innermost circular and longitudinal muscle layers, but less
      intensively in the outer circular layer. Weak cGK-I staining occurred in nerve
      cells within the myenteric and submucosal plexus. Conclusively the key enzymes of
      the NO signaling pathway are differentially distributed: Occurrence of nNOS
      exclusively in neurons and the presence of sGC and cGK-I predominantly in ICC
      suggest a sequence of neuronal NO release, activation of ICC, and consecutive
      smooth muscle relaxation. ICC of the DMP seem to be the primary targets for
      neurally released NO.

PMID- 11572087
TI  - Pituitary adenylate cyclase activating peptide (PACAP) immunoreactivity in the
      ureter of the duck.
AB  - The presence, distribution and colocalisation of pituitary adenylate cyclase
      activating peptide (PACAP) immunoreactivity have been studied in the duck ureter
      by using Western blot analysis, radioimmunoassays (RIA) and immunohistochemistry.
      The presence of both PACAP-38 and PACAP-27 was demonstrated, PACAP-38 being the
      predominant form. PACAP-immunoreactive fibres and neurons were found in all the
      ureteral layers. Double immunostaining showed that PACAP was almost completely
      colocalised with vasoactive intestinal peptide (VIP). Moreover, PACAP was found
      in substance P (SP)-containing ureteral nerve fibres and in SP-containing dorsal
      root ganglion neurons. RIA performed on denervated ureters demonstrated that
      almost half of the ureteral PACAP was extrinsic in origin. These findings suggest
      that, in birds, PACAP has a role in diverse nerve-mediated ureteral functions.

PMID- 11572089
TI  - Identification of estrogen-responsive genes in chick liver.
AB  - Identification of targets of estrogen is an important step in understanding the
      mechanisms of estrogen action. A two-step strategy was developed to identify
      estrogen-responsive genes (ERGs) in chick liver. Initially, differential-display,
      reverse transcription polymerase chain reaction (DDRT-PCR) was introduced to
      isolate ERGs. Isolated ERGs were then analyzed using Northern blot hybridization.
      A number of differentially expressed cDNA fragments were isolated following
      estrogen exposure. Four cDNA fragments that displayed dramatic change after
      estrogen administration were identified as liver adenylosuccinate lyase (ADL),
      phenobarbital-inducible cytochrome P-450 (CYP450), ovoinhibitor, and glutathione
      dependent prostaglandin D2 synthase (PGDS). Time sequence analysis showed that
      estrogen-induced alteration occurred as early as 0.5 h and peaked between 1 and 4
      h after estrogen exposure. Nuclear runoff assay indicated that estrogen
      significantly increased the transcription rate of these genes. To determine
      whether the observed alteration was due to the direct effect of estrogen, protein
      synthesis was inhibited by cycloheximide (CHX) during stimulation by estradiol,
      Estrogen-mediated upregulation of PGDS was completely abolished by a concurrent
      treatment with CHX, suggesting that its activation requires the participation of
      some newly synthesized factor(s). In contrast, CHX did not affect the expression
      of other genes, indicating the alteration is a direct response to estrogen. In
      conclusion, ADL, CYP450, ovoinhibitor, and PGDS represent the novel targets of
      estrogen, which regulates the transcriptional activity of these genes.

PMID- 11572088
TI  - Expression and localization of leptin receptor in the normal rat pituitary gland.
AB  - Leptin receptor (leptin-R) is a polypeptide consisting of a single transmembrane
      spanning component. Recent studies performed by reverse transcriptase polymerase
      chain reaction (RT-PCR) have shown the production of leptin-R in various tissues
      including the pituitary, hypothalamus and reproductive organs. The localization
      of leptin-R protein in the pituitary gland, however, has not been extensively
      studied. This study deals with the expression of leptin-R in the normal rat
      pituitary gland, which was disclosed primarily in the plasma membrane fraction by
      immunoblotting and immunohistochemical staining methods. Double
      immunohistochemical staining revealed that the colocalization of leptin-R and
      anterior pituitary hormone expression was seen mainly in growth hormone (GH)
      secreting cells (97.4 +/- 1.3%; GH-positive cells/leptin-R-positive cells), but
      in less than 1% of prolactin (PRL)-, adrenocorticotropic hormone (ACTH)-, thyroid
      stimulating hormone-beta (TSH beta)- and follicle-stimulating hormone-beta (FSH
      beta)/luteinizing hormone-beta (LH beta)-positive cells. In contrast, leptin was
      localized most frequently in FSH beta/LH beta- and less frequently in TSH beta
      positive cells. The above findings suggest that, in the rat anterior pituitary
      gland, there are paracrine relationships between leptin-producing cells and cells
      with leptin-R, which may regulate the function of GH cells.

PMID- 11572090
TI  - Ultrastructural changes in pancreatic beta cells treated with NGF and dbcAMP.
AB  - Nerve growth factor (NGF) induces morphological and physiological changes in
      cultured pancreatic beta-cells, including the extension of neurite-like
      processes. This latter effect is potentiated by dibutyryl cAMP (dbcAMP). beta
      cells cultured under these conditions maintain their immunoreactivity to insulin
      and gamma-amino-butyric acid (GABA). NGF, dbcAMP, and high glucose concentrations
      also increase the expression of the GABA-synthesizing enzyme glutamic acid
      decarboxylase-65 in cultured beta-cells. The aim of this work was to study the
      effect of NGF alone or in combination with dbcAMP on pancreatic beta-cell
      ultrastructural morphology, after 10 days in culture. We used light microscopy,
      scanning electron microscopy, and transmission electron microscopy to analyze the
      modifications in cell surface and neurite-like projections. Morphometric analysis
      showed that NGF and/or dbcAMP treatment substantially increased the insulin and
      GABA content in granules and rough endoplasmic reticulum. Given that pancreatic
      beta-cells express NGF receptors and that NGF is synthesized and secreted by beta
      cells, these results further suggest that NGF could have trophic actions on
      pancreatic hormone synthesis and/or storage.

PMID- 11572091
TI  - Urethral seam formation and hypospadias.
AB  - Knowledge of the formation of the normal male urethra may elucidate the etiology
      of hypospadias. We describe urethral formation in the mouse, show the
      similarities and relevance to human urethral development, and introduce the
      concept of the epithelial seam formation and remodeling during urethral
      formation. Three mechanisms may account for epithelial seam formation: (1)
      epithelial-mesenchymal transformation similar to that described in the fusion of
      the palatal shelves, (2) apoptosis, and/or (3) tissue remodeling via cellular
      migration. Urethral development in the embryonic mouse (14-21 days of gestation)
      was compared with urethral formation in embryonic human specimens (8-16 weeks of
      gestation) by using histology, immunohistochemistry, and three-dimensional
      reconstruction. The urethra forms by fusion of the epithelial edges of the
      urethral folds, giving a midline epithelial seam. The epithelial seam is
      remodeled via cellular migration into a centrally located urethra and ventrally
      displaced remnant of epithelial cells. The epithelial seam is remodeled by
      narrowing approximately at its midpoint, with subsequent epithelial migration
      into the urethra or penile skin. The epithelial cells are replaced by mesenchymal
      cells. This remodeling seam displays a narrow band (approximately 30 microns
      wide) of apoptotic activity corresponding to the mesenchymal cells and not to
      epithelial cells. No evidence was seen of the co-expression of cytokeratin and
      mesenchymal markers (actin or vimentin). Urethral seam formation occurs in both
      the mouse and the human. Our data in the mouse support the hypothesis that seam
      transformation occurs via cellular migration and not by epithelial mesenchymal
      transformation or epithelial apoptosis. We postulate that disruption of
      epithelial fusion remodeling, and cellular migration leads to hypospadias.

PMID- 11572092
TI  - Characterization of cultured human prostatic epithelial cells by cluster
      designation antigen expression.
AB  - Cultured prostatic epithelial cells have been extensively studied as a model of
      prostate biology. What is the lineage relationship of the cultured cells to the
      epithelial cell types in tissue? How different are cultured cells derived from
      tumor tissue to those derived from benign tissue? Expression of cluster
      designation (CD) cell surface molecules has been shown to be useful in
      characterizing cells according to lineage. A CD profile was therefore generated
      for cultured human prostatic epithelial cells and compared with those previously
      established for basal and luminal epithelial cells in the prostate. Presence of
      CD44, CD49b, CD49f, and CD104 and absence of CD57 suggests that cultured cells
      were derived from basal cells of prostatic tissues. However, expression of
      certain CD antigens characteristic of luminal epithelial cells was also observed
      in subpopulations of cultured cells. The pattern of CD antigens in cultured cells
      reflects a phenotype similar to that of transit-amplifying cells that have been
      described in the prostate. Several CD antigens were found expressed by both
      cultured prostatic epithelial and stromal cells, and are probably associated with
      cell proliferation. The CD profiles of cultured epithelial cell strains derived
      from normal compared with malignant tissues were notably similar to each other
      and to that of the prostate cancer cell line PC-3. We conclude that cells in
      culture retain expression of certain lineage-characteristic CD antigens.
      Furthermore, CD antigens can define subpopulations of cells with differential
      gene expression.

PMID- 11572094
TI  - Ultrastructural co-localization of TFF3-peptide and oxytocin in the neural lobe
      of the porcine pituitary.
AB  - TFF-peptides (formerly P-domain peptides, trefoil factors) are typical secretory
      products of many mucous epithelial cells. TFF3 is also synthesized in
      oxytocinergic neurons in the paraventricular and supraoptic nuclei of the human
      hypothalamus. Here, TFF3 and oxytocin are shown to be co-localized within the
      same secretory vesicles in the neural (posterior) lobe of the procine pituitary
      by means of immunoelectron microscopy. Relatively large amounts of TFF3, but not
      TFF1 and TFF2, are present in the neural lobe of the porcine pituitary, where it
      is probably released into the bloodstream.

PMID- 11572093
TI  - Dynamic changes in protein components of the tight junction during liver
      regeneration.
AB  - The construction of the hepatocyte tight junction is one of the most important
      events during liver regeneration leading to the reorganization of the bile
      canaliculi and the repolarization of hepatocytes after cell division. To
      understand this event at the molecular level, we examined the expression of tight
      junction proteins by Western blot analysis and their cellular localization by
      immunofluorescence microscopy in regenerating rat liver after two-thirds
      hepatectomy. The levels of tight junction components such as claudin-3, ZO-1 and
      atypical protein kinase C (PKC)-specific interacting protein (ASIP) increased two
      to three-fold over control levels in coordination with a peak 2-3 days after
      partial hepatectomy, whereas occludin levels remained unchanged. The bile
      canaliculi outlined by tight junction components and actin filaments reveal
      significant morphological changes from 2-3 days after partial hepatectomy. During
      this period, claudin-3/ZO-1 and ASIP/ZO-1 were nearly co-localized, whereas
      occludin was locally reduced or almost absent on the bile canaliculi outlined by
      ZO-1 staining. The uncoupled localization of F-actin and tight junction
      components was often observed. The function of hepatocytes, as revealed by the
      serum bile acids level, was distorted temporally at an early stage of
      regeneration but mostly restored 3 days after partial hepatectomy. These
      observations suggest that the de novo construction of tight junctions proceeds
      mainly 2-3 days after partial hepatectomy in parallel with the cell polarization
      required for hepatocyte function. However, the complete normalization of the
      composition of the tight junction components, such as occludin and the
      association with F-actin, requires additional time, which may support the
      regeneration of fully polarized normal hepatocytes.

PMID- 11572095
TI  - Histochemical survey of transmitters in the central ganglia of the gastropod
      mollusc Phestilla sibogae.
AB  - The aeolid nudibranch Phestilla sibogae is well studied in terms of its larval
      nervous system and neuronal involvement in metamorphosis. Central neurones in the
      adult have also been identified anatomically and electrophysiologically. We
      describe the neurotransmitter contents of these neurones and provide details of
      neuritic projections and developmental changes during growth (3 to 18 mm body
      length). Central ganglia from specimens of all sizes contained 100-115 serotonin
      immunoreactive neurones, some of which appeared to be homologues of cells
      identified in other gastropods. Tyrosine hydroxylase immunoreactivity and
      aldehyde-induced fluorescence marked a common set of 28-30 catecholaminergic
      neurones located anteriorly in the cerebropleural ganglia and laterally in the
      pedal ganglia. Ganglionic neuropile and nerve trunks also contained many
      catecholaminergic fibres. About 65-100 intensely labelled FMRFamide
      immunoreactive neurones were located symmetrically throughout the central
      ganglia, although one population was located only in the right pedal ganglion.
      Another 40-45 FMRFamide-immunoreactive neurones were weakly or variably stained.
      Central ganglia also contained 27-29 intensely labelled pedalpeptide
      immunoreactive neurones, including those that were apparently homologues of cells
      previously described in Tritonia diomedea, and 16-19 weakly labelled pedal
      peptide-immunoreactive neurones, including giant cerebropleural neurones
      coexhibiting FMRFamide immunoreactivity. Little cell addition involving any
      transmitter phenotype occurred as animals grew in body length, body growth being
      accommodated by growth in the size of individual cells, consistent with an
      approximate doubling in the size of the ganglia themselves.

PMID- 11572096
TI  - Yolk granules are differentially acidified during embryo development in the stick
      insect Carausius morosus.
AB  - Newly laid eggs of stick insects comprise a unique fluid ooplasm that is
      gradually partitioned into a number of yolk granules by invasion of secondary
      vitellophages. This study aimed at establishing how yolk granules become
      acidified in the course of embryonic development. Data show that acidified yolk
      granules are rather scarce and randomly distributed in vitellophages of early
      embryos, while they tend to increase gradually in number as development proceeds
      to completion. Yolk granule acidification is progressively more inhibited in the
      presence of increasing concentrations of chloroquine, monensin and bafilomycin. A
      pro-protease was identified cytochemically and by immunoblotting in yolk extracts
      of progressively more advanced embryos. A specific monoclonal antibody raised
      against this pro-protease helped to demonstrate that it is gradually processed to
      yield a lower molecular weight polypeptide as development proceeds to completion.
      This latter polypeptide was identified as a protease using electrophoresis in
      polyacrylamide gels containing yolk extracts. Simultaneous administration of a
      fluorescent substrate for cysteine protease and an acidotropic probe produced
      superimposable labelling patterns, suggesting that only acidified yolk granules
      possess a proteolytic activity. On the other hand, yolk granules probed
      simultaneously for acidification and latent pro-protease yielded labelling
      patterns partially superimposed. Pro-protease labelling is gradually lost as yolk
      granules are progressively more acidified during development. Distinct labelling
      patterns were also obtained in vitellophages processed for the simultaneous
      detection of pro-protease and protease, suggesting that the two activities are
      expressed by different yolk granule populations, and that one is gradually
      converted into the other as time goes by.

PMID- 11572097
TI  - Identification of respiratory and ion-transporting epithelia in the phyllosoma
      larvae of the slipper lobster Scyllarus arctus.
AB  - Phyllosoma larvae of the Palinura lack a branchial cavity and gills. In the
      phyllosoma, gas and ion exchanges that occur at the level of the gill in the
      adult must occur in other parts of the body or through the entire body. The
      objective of this study was to localize epithelia bordering the body of the
      phyllosoma larvae that had features comparable to those of the gill epithelia of
      adult decapods. The first phyllosoma instar of the small Mediterranean slipper
      lobster Scyllarus arctus was studied. First, we used a silver nitrate staining
      method to identify parts of the body with high ionic permeability. Confocal laser
      scanning microscopy with a fluorescent vital stain for mitochondria,
      dimethylaminostyrylmethylpyridiniumiodine (DASPMI), was then used to localize
      cells with a high density of mitochondria. Next, an ultrastructural study of
      selected epithelia was carried out. A thick (5 microns) mitochondria-rich
      epithelium covers the ventral side of the cephalic shield; its cells are
      characterized by the presence of well-developed apical infoldings adjacent to the
      cuticle. This part of the body has a high ionic permeability as indicated by a
      positive silver nitrate staining. The ventral mitochondria-rich epithelium might
      be involved in active ion transport. The rest of the body, particularly the
      dorsal side of the shield and the appendages, shows a lower ionic permeability
      (no positive silver nitrate staining) and is limited by a thin (1 micron)
      epithelium with low numbers of mitochondria. This epithelium exhibits features of
      a typical respiratory epithelium.

PMID- 11572098
TI  - Nitric oxide synthase in the spinal cord of the frog, Xenopus laevis.
AB  - The expression of nitric oxide synthase was investigated in the spinal cord of
      the South African clawed frog by NADPH diaphorase histochemistry and
      immunohistochemistry. The dorsal field contained many strongly positive neurons
      and a dense plexus of processes. Only few nitric oxide synthase-positive cells
      occurred in the lateral and central field. Motoneurons were negative. A dense
      accumulation of stained neurons was located dorsal and dorsomedial to the
      motoneurons. The white matter harbored many positive fibers. These were most
      abundant in the dorsal funiculus, and obviously consist of nonprimary projections
      to the brainstem. These results suggest that nitric oxide represents a widely
      used messenger molecule in the frog spinal cord, in particular with respect to
      the processing of sensory information.

PMID- 11572099
TI  - [Use of electroconvulsive therapy in psychiatry].
AB  - Electroconvulsive therapy (ECT) has antidepressive and antipsychotic effects.
      Since being introduced in Italy in 1938, its mode of action has still not been
      clarified. Treatment modalities have changed in many ways. ECT, in which a
      generalized epileptic seizure is provoked by electrical stimulation of the brain,
      is performed under short intravenous anesthesia and muscle relaxation.
      Considering careful previous clinical examination and anesthesiological and
      internal counterindications, ECT is a very safe form of treatment. Single cases
      of persisting memory impairment were described after the formerly common
      bilateral sinus wave stimulation. However, recent developments such as brief
      pulse stimulation, unilateral electrode placement, and individual stimulus
      titration (on the basis of EEG monitoring) make memory impairment as a
      consequence of ECT a rare event which mostly remits completely in 4-8 weeks.
      Today, ECT is performed mainly in patients suffering from severe, therapy
      resistant affective or schizophrenic disorders. Pernicious catatonia and the
      neuroleptic malignant syndrome are emergency indications. Adequate ECT treatment
      requires a series of 6-12 individual sessions (every second or third day). In
      therapy-resistant depression, for which the greatest number of data are
      available, the response rate lies between 50 and 60%. This has been confirmed by
      a descriptive analysis of all ECT treatments at the Department of Psychiatry,
      University of Vienna, between 1994 and 2000. There is a need for controlled
      studies on continuation therapy subsequent to successful ECT.

PMID- 11572100
TI  - [Evaluation of suicide prevention measures. Current state of research and
      resulting implications].
AB  - Even though the WHO recommended the implementation of regional and nationwide
      suicide-preventive activities, there is little evidence of their efficacy. The
      goal of this review is to discuss the different approaches concerning suicide
      prevention. On the one hand, strategies which try to improve the diagnosis and
      medical care of special high-risk groups are presented. On the other hand,
      population-based strategies are discussed. The main targets here are promoting
      public awareness, optimising primary care, restricting the presentation of
      suicides in mass media, and restricting the access to means for suicide. The
      combination of high-risk and population-based strategies might hold promise for
      the best effects.

PMID- 11572101
TI  - [Psychiatric emergencies in preclinical emergency service; incidence, treatment
      and evaluation by emergency physicians and staff].
AB  - Preclinical psychiatric emergency situations (PES) rank third in frequency of
      calls in the German emergency medical system (EMS). However, few data exist
      concerning relevance and treatment of PES. The aim of this study was to
      investigate this relevance in preclinical EMS and its appraisal by emergency
      physicians and paramedics. The protocols filled in by EMS physicians on emergency
      duty in a German district were evaluated concerning PES. In addition, the
      emergency physicians and paramedics of the district were asked to complete a
      validated questionnaire concerning the importance, their own understanding of
      PES, and interest in training programs. With 9.2%, preclinical PES ranked third
      in frequency of all EMS calls. The most frequent case was substance abuse
      disorder (70%), followed by suicide attempts or ideation (33%). Specific therapy
      for psychiatric disorders is hardly ever performed. Emergency physicians and
      paramedics estimated the importance of knowledge about PES as high but rated
      their own knowledge as poor. Assessing five typical PES, emergency physicians
      gave the correct diagnoses in 71% of cases (paramedics 39%) and the correct
      therapy in 32% (paramedics 14%). The interest in training programs was
      significantly higher in experienced EMS physicians. Preclinical PES is a relevant
      diagnosis within EMS and correct treatment is hampered by limited knowledge.
      Sufficient training is not yet available, although programs are necessary and the
      willingness to participate in them is high.

PMID- 11572102
TI  - [Patient assaults of staff; a prospective study of the incidence, circumstances
      and sequelae].
AB  - Patient assaults in psychiatric hospitals result in a considerable number of job
      related accidents and personnel absenteeism. The aim of this study was to assess
      the incidence of assaults, analyze trigger situations, and describe physical and
      psychological consequences among staff members. Within a study period of 6
      months, all apparently aggressive physical contacts between patients and staff in
      six northwest German psychiatric hospitals were assessed. Patient and staff
      variables, situational characteristics, and physical as well as psychological
      consequences were evaluated. During this time, 155 assaults on 170 staff members
      were reported. Before the assaults, most of the patients showed early signs of
      aggression as an indication of situational worsening. Work absenteeism following
      the assaults was observed in 5% of the affected staff. In 14%, symptoms of post
      traumatic stress could be diagnosed using the questionnaire version of the PTSD
      interview. In conclusion, the study results suggest that additional training of
      younger personnel and implementation of conflict management schemes could help to
      prevent these assaults.

PMID- 11572103
TI  - [Ethical conflicts in involuntary treatment of schizophrenic patients; decision
      making and in influential factors in three prototype cases].
AB  - Three case reports of patients with schizophrenia were presented to a sample of
      520 persons (25.1% psychiatrists, 3.7% psychologists, 8.1% social workers, 14.6%
      nurses, and 48.6% others). The decisions for involuntary admission to a
      psychiatric hospital and involuntary treatment were questioned. In case 1 (young
      man, first episode, delusions, extreme social withdrawal), 71.7% supported
      admission to hospital and 62.7% were in favor of neuroleptic treatment. In case 2
      (woman with disorganized syndrome beating her 74-year-old mother), 84.6%
      supported hospitalization and 78.8% neuroleptics. In case 3 (relapsed multi
      episode patient, increasingly neglected, delusional, and socially withdrawn),
      56.3% supported hospitalization and 52.7% neuroleptics. Generally, psychiatrists'
      decisions were very similar to those of other professionals and laypersons, while
      social workers more often rejected involuntary treatment. After professional
      status, multivariate analyses revealed older age as the most significant variable
      for support of involuntary treatment. Frequency of experience with mentally ill
      persons were only weak predictors or not significant.

PMID- 11572104
TI  - [Effects of new cognitive-behavioral therapy programs for improvement of specific
      social skills of schizophrenics--a controlled study].
AB  - Based on the Integrated Psychological Therapy (IPT) for schizophrenia patients,
      the Berne group developed three specific cognitive behaviour therapy programmes
      for treating residential, vocational, and recreational functioning. We added new
      cognitive-emotional methods to these programmes that were devised especially for
      schizophrenia patients, taking into consideration the criticism of traditional
      social skill training methods. In the present multicentre study, these new
      programmes (experimental group) were compared with a traditional social skills
      training programme (control group, IPT "Social Skills" subprogramme). Both the
      therapy and aftercare phase each lasted 12 weeks and the follow-up phase 1 year.
      Assessment instruments covered psychopathology, cognitive functioning, and social
      adjustment. Higher ratings of global treatment effects and significant reductions
      in symptoms were obtained in the experimental group. In view of the favourable
      results, these newly designed social skill training programmes may replace more
      conventional therapy approaches in the future.

PMID- 11572105
TI  - [Medical ethics of heroin prescription by physicians].
AB  - Due to increasing public health and social issues as secondary problems of opiate
      dependence (e.g. mortality, risk of HIV- and hepatitis infection, high rate of
      criminal activities) heroin prescription to opiate addicts has been suggested.
      Scientific data do not yet allow a solid evaluation of this treatment. As
      generally accepted, the main criteria for an ethical evaluation of new treatments
      are a) beneficence (duty to help patients further their important and legitimate
      interests), b) respect for the patient's autonomy and c) social justice in the
      allocation of the limited resources of the health care system. Ethical problems
      of heroin prescription relate to the differentiation between medical concern for
      the individual patient's health and the public interests in reducing social
      problems, the problematic capability of addicts of a balanced evaluation of
      heroin prescription and economic considerations of the costs of heroin
      prescription in comparison with other forms of treatment of opiate addiction,
      especially methadone maintenance treatment.

PMID- 11572106
TI  - [Polygraphy of a panic attack].
AB  - We studied a 24-year old female patient with Type 1 diabetes mellitus suffering
      for 4 weeks from a major depressive episode combined with panic disorder without
      agoraphobia. A spontaneous panic attack was serendipitously recorded by polygraph
      while the subject was at rest. Electrocardiogram, finger blood-flow, respiratory
      rhythm and muscle tone (forearm, forehead) were recorded. A triphasic course
      consisting of a "dynamic phase" (appr. 80 s) preceded by a discrete "initial
      phase" (appr. 140 s) and a "declining phase" (appr. 180 s) was observed. The
      dynamic phase is characterized by an acute increase of fingertip vasoconstriction
      and heart rate. The patient was not aware of the panic attack before the dynamic
      phase. The recognisable central regulation confirms previously published findings
      indicating a sympathetic-norepinephrine activation at the beginning of the panic
      attack without activating the musculoskeletal system. Furthermore, a paradoxical
      phenomenon involving heart and respiratory rate was observed before the onset of
      anxiety, i.e. an increase of the heart rate and a simultaneous decline of the
      respiratory rate, suggesting a non-antagonistic regulation of the ergotropic
      trophotropic system. The autonomic state of the patient points to a lability in
      homeostasis from which panic attacks as a form of CNS response could develop.

PMID- 11572107
TI  - [Incompatibility of olanzapine and amisulpride in multisystemic myotonic
      myopathy].
AB  - There is evidence for the occurrence of psychopathological symptoms in the adult
      form of myotonic dystrophy such as disturbance of concentration and memory,
      chronic depression, disturbed social behaviour, mental retardation, and
      hypersomnia. In this report we present a patient suffering from multisystemic
      myotonic myopathy without a cytosine-thymine-guanine [corrected] repeat expansion
      on chromosome 19q13.3 and schizophrenia. In this patient, a severe increase of
      creatine kinase (CK) occurred during treatment with olanzapine and amisulpride.
      The following risperidone medication was well tolerated without side effects.
      Susceptibility for malignant hyperthermia was detected by a positive in vitro
      contracture test. The occurrence of elevated muscle enzymes during treatment with
      atypical neuroleptics is suspicious as a possible side effect of neuroleptic
      medication and muscle disease.

PMID- 11572108
TI  - [Repetitive transcranial magnetic stimulation (rTMS) in the acute and long-term
      therapy of refractory depression--a case report].
AB  - We report on a patient with therapy-resistant major depression according to DSM
      IV criteria who has been hospitalized for 60 months during the last 7 years. Not
      even five electroconvulsive therapy (ECT) series (61 single applications) brought
      lasting remission of symptoms. As cognitive deficits developed and prolonged
      postnarcotic recovery times were observed, further ECT was contraindicated. The
      left frontal cortex was chosen as the target site for repetitive transcranial
      magnetic stimulation (rTMS) treatment. For identification, a neuronavigational
      system was used that allows online monitoring of the position of the magnetic
      coil in relation to the individual cortex. The therapeutic progress was monitored
      by standardized psychiatric ratings (HAMD, BDI). In addition, cognitive
      performance was tested during the course of treatment. Only a few rTMS
      applications already caused an obvious brightening in mood, remission of
      depressive delusional symptoms, and an increase in personal interests and
      activities. After 4 weeks of daily treatment, the patient was discharged from the
      ward. The rTMS treatments and psychotherapeutic counseling have been continued on
      an outpatient basis. Thus, pharmaco- and psychotherapeutic interventions combined
      with rTMS led to persistent symptom remission and social reintegration.

PMID- 11572109
TI  - [Rudolf Virchows' view of malignant growth].

PMID- 11572110
TI  - [Pathology of important diseases of endocrine organs (excluding the thyroid)].
AB  - Basic principles of classification of tumors of the pituitary, parathyroid
      glands, adrenals, paraganglionic system and endocrine pancreas and the
      differential diagnosis from non-endocrine tumors are presented. There are no
      uniform criteria of malignancy and common neuroendocrine immunohistological
      markers for unequivocal identification, as each organ has its own criteria. For
      pituitary tumors invasive growth is not a sign of malignancy, but only
      metastases. For tumors of the adrenal cortex a histopathological score has to be
      used for proving dignity. For pheochromocytomas, structural criteria (mitoses,
      angioinvasion) and immunostaining (S-100 protein, p53, Ki-67) are important.
      Endocrine tumors of the pancreas behave differently if they are angioinvasive or
      if they show more than two mitoses per 10 HPF, more than 2% Ki-67 positive nuclei
      or a size of more than 2 cm in diameter. They are malignant if gross local
      invasion or metastases are demonstrable. Clinical data have to be included in
      pathohistological reports. In many cases immunostaining in addition to structural
      analysis will be necessary.

PMID- 11572111
TI  - [The increasing importance of tumor and tissue banks in the light of genomic and
      proteomic research].
AB  - Recent technological advances in genome and proteome research offer new
      perspectives for diagnosis and therapy. The DNA chip technology as well as high
      resolution two-dimensional gel electrophoresis in combination with mass
      spectrometry is able to provide comprehensive information on gene and protein
      expression patterns, which allow insights into the dynamic and functional aspects
      of diseases. The application of these techniques depends on the availability of
      unfixed fresh or cryopreserved tissue with short ischaemia time. For this reason
      tissue banks are of increasing importance. The pathologist with his expertise and
      responsibility for histopathological diagnosis, plays a central role in the
      collection of the human tissues, in accordance with medical, legal and ethical
      standards, not only for diagnostic purposes, but also for research. The
      scientific value of a tissue bank is markedly increased if tissue samples are
      accompanied by detailed patient data as well as blood samples. Informed consent
      given by the patient is an essential requirement for the use of human tissue
      banks in biomedical research. The informed consent should not be restricted to
      scientific investigations but also include the potential commercial use of the
      data generated.

PMID- 11572112
TI  - [Pathology and pathomorphologic diagnosis of germ cell tumors of the testis].
AB  - Testicular germ cell tumors are rare and comprise about 90% of all testis tumors.
      Genetic factors may play a role in the pathogenesis as can be deduced by a higher
      family-linked incidence and the p53 gene seems to be important in the development
      of these tumors which derive from a malignant transformed germ cell. Testicular
      intraepithelial neoplasia (TIN) may differentiate in two directions, namely into
      seminomas which comprise nearly 50% of all testicular germ cell tumors and non
      seminomas. Since the term "differentiated teratoma" may be misleading, we propose
      the use of the term "teratoma" only. A preoperative diagnosis by biopsy is not
      indicated. An exact postoperative diagnosis including all necessary
      classifications, particularly the WHO and the TNM classifications, requires a
      very careful preparation of the resected specimen. The histological diagnosis
      should list all the different types of the WHO classification and the percentage
      of the tumor should be indicated, at least for embryonal carcinomas. For T
      categorisation in the TNM classification, the presence of invasion of veins or
      lymph vessels is important. Documentation, preferably in the form of a standard
      checklist, is strongly recommended.

PMID- 11572113
TI  - [Proliferation rate of small cell lung carcinoma. A cytomorphometric parameter
      with prognostic significance].
AB  - AIM: Evaluation of prognosis-associated parameters in patients with small cell
      lung carcinoma. MATERIAL AND METHODS: Biopsies of 46 patients suffering from a
      non-treated small cell lung carcinoma were stained with Feulgen and
      immunohistochemically with Ki-67 antibody. The integrated optical density (IOD)
      and proliferation rate was measured by syntactic structure analysis and
      correlated with survival. RESULTS: About 85% of patients had a smoking history
      (46 pack years on average). The median survival time was 13.5 months, the
      proliferation rate (Ki-67 positive tumor cell nuclei) 68.2% and S-phase
      percentage 9.2%. Ot average, 25 proliferating tumor cell nuclei formed clusters
      (mean diameter 95 microns). The prognosis was associated with the proliferation
      rate (p < 0.04), tumor stage (stage I versus lib, p < 0.05), at threshold limits
      with S-phase rate (p < 0.07) and serum levels of LDH and NSE (p < 0.06 and p <
      0.07 respectively). CONCLUSIONS: Immune histochemical determination of the Ki-67
      protein is a useful method to estimate the prognosis of patients with small cell
      lung carcinoma.

PMID- 11572114
TI  - [Inflammatory fibroid polyps of the gastrointestinal tract].
AB  - Inflammatory fibroid polyps of the gastrointestinal tract represent a relatively
      rare entity. Although the histopathological classification, the etiology and the
      pathogenesis of this lesion remains unclear, the biological dignity is commonly
      understood as benign. Nevertheless, these polyps are able to cause
      gastrointestinal bleeding, intestinal obstruction or intussusception which often
      provides the indication for surgical treatment. In endoscopical biopsies
      unexpected difficulties for the pathologist may arise from the fact that these
      uncommon lesions often show a submucosal growth pattern. With reference to two
      case reports, the clinical, diagnostic and histopathological aspects of
      inflammatory fibroid polyps will be discussed. An additional literature review of
      the etiology, immunohistochemistry and differential diagnosis is presented.

PMID- 11572115
TI  - [Acute segmental hemorrhagic antibiotic-associated colitis].
AB  - Three cases of acute segmental hemorrhagic antibiotic-associated colitis are
      described occurring in three male adults between 30 and 33 years of age after
      treatment with oral ampicillin or amoxicillin because of upper respiratory tract
      infection, tonsillitis, or HLO eradication therapy, respectively. All presented
      with cramping abdominal pain and bloody diarrhoea of acute onset, however,
      microbial analysis of fecal samples was negative. Endoscopy showed right-sided
      segmental hemorrhagic colitis. Histopathological examination demonstrated edema,
      patchy superficial hemorrhage and a scattered predominantly mononuclear
      infiltrate of the lamina propria. The surface epithelium was partly desquamated
      and displayed foci of grouped intraepithelial red blood cells. All patients
      spontaneously recovered after discontinuation of antimicrobial therapy. The value
      and limitations of diagnostic features are discussed with respect of the
      literature.

PMID- 11572116
TI  - [Primary renal hemangiosarcoma. Case report and review of the literature].
AB  - Primary hemangiosarcoma of the kidney is a very rare tumor for which only 23 case
      reports appear in the literature worldwide. An additional case of renal
      angiosarcoma in an adult is reported. The patient developed local tumor
      recurrence with multiple metastases within 4 weeks and died although there was no
      evidence of metastases at the time of nephrectomy.

PMID- 11572117
TI  - [Complex pulmonary vessel alterations in an aorto-pulmonary window in adulthood].
AB  - An aorto-pulmonary window (aorto-pulmonary septal defect) is considered to be a
      rare congenital cardiac malformation. We report the case of a patient with an
      unrepaired congenital aorto-pulmonary window 1.4 cm in size which is the largest
      aorto-pulmonary septal defect yet reported. This patient died at the age of 58
      not from the congenital cardiac malformation but from the after-effects of a
      pulmonary adenocarcinoma diagnosed 2 years previously. Interestingly, the long
      standing, persistent pulmonary hypertension correlated well with the varying
      pathomorphological changes seen in the pulmonary vessels. In addition to the
      complex morphological signs due to the pulmonary hypertension such as the
      extensive aneurysms found in the left and right main pulmonary arteries (first
      report of this size), pulmonary vessels with relatively few pathomorphological
      changes were also found. Hence this first report of such a long survival of a
      patient with a comparatively large aorto-pulmonary septal defect demonstrates a
      surprising variety of pathomorphological alterations seen in the pulmonary
      arteries in the face of excessive pulmonary hypertension. These alterations could
      be the result of peripheral aneurysmatic formations and thrombembolic stenoses of
      the lobular or segmental arteries and might provide an explanation for the long
      survival of this particular congenital cardiac malformation. All these varying
      findings in the pulmonary arteries emphasise the fact that the pathomorphological
      findings in lung biopsies might not be representative of the whole lung.

PMID- 11572118
TI  - [Highlights of the 8th Baltic-German Symposium for Pathology in Tallinn/Reval
      (Estonia)].

PMID- 11572119
TI  - [Therapy of cartilage damage--more current than ever].

PMID- 11572120
TI  - [Surgical therapeutic possibilities of cartilage damage].
AB  - Therapy of cartilage damage is a frequent problem, especially in the young and
      active patient. For the treatment of a cartilage damage we have to consider the
      size of the defect, age and weight of the patient, meniscal tears, ligament
      instabilities and varus-/valgus-malalignment. Lavage, shaving and debridement are
      only sufficient for a short time and have no long term effect. Abrasio and
      drilling could be useful in eldery people. Microfracturing seems to be an
      effective alternative for small defects. The restoration of the cartilage surface
      with the use of autologous chondrocyte transplantation, osteochondral autograft
      transplantation and posterior condyle transfer seems to be an adequate treatment
      for younger patients.

PMID- 11572121
TI  - [Minimizing allogeneic blood transfusion in knee prosthesis implantation].
AB  - The goal of blood management in orthopedic and trauma surgery is to minimize
      exposure to allogenic blood transfusion in elective surgical procedures. Pre-,
      intra- and postoperative techniques are available. In a retrospective study at
      our department we could show, that postoperative reinfusion in primary knee
      arthroplasty is an effective way to avoid allogenic blood transfusion. We
      evaluated two groups of totally 40 patients. Group I (20 patients) underwent
      collection of postoperative drainage blood and reinfusion (blood conservation
      system, CBC II ConstaVac, Stryker instruments), group II (20 patients) was
      treated without postoperative reinfusion. Group II required per patient 1.3 units
      of allogenic blood (totally 26 units), group I needed only 0.25 units of
      allogenic blood per patient (totally 5 units) by using the same guidelines for
      transfusion in both groups. There were similar preoperative and postoperativ
      hemoglobin and hematocrit levels in both groups. We recommend the use of
      postoperative reinfusion in addition with other blood saving techniques to reduce
      allogenic blood transfusion in primary knee arthroplasty.

PMID- 11572122
TI  - [Management of proximal scaphoid bone pseudarthroses and fractures with the mini
      Herbert screw via a dorsal approach].
AB  - 32 patients, aged 16 to 49 years, were treated by osteosynthesis using the
      Herbert mini screw. The indications were five fractures (type B3, Herbert
      classification), two delayed unions (type C) and 25 nonunions (type D1 to D3,
      Filan and Herbert classification). Six patients received no bone grafts, 19
      received cancellous bone graft from the radius. An interpositional iliac crest
      bone graft was used in four, and a vascularized bone graft from the distal radius
      in three cases respectively. The average postoperative immobilisation in a
      forearm splint was nine weeks. 26 patients could be recruited for clinical follow
      up at an average of 14.5 months. The radiological results were assessed in 30
      cases (94%). Bony consolidation was achieved in 26 cases (100% of the fractures,
      84% of the nonunions). In three cases a loosening of the screw, and in three
      further cases a dislocation into the radiocarpal joint were observed. A humpback
      deformity was present in four cases. Three patients showed a persisting nonunion,
      one patient a fibrous union. Early degenerative changes of the radiocarpal joint
      were observed in six cases. The clinical follow up examination showed an average
      grip strength of 91% (JAMAR II), 94% for the three finger, and 95% for the pinch
      grip compared to the contralateral side. The mean postoperative pain score on the
      visual analog scale was one for resting conditions, eleven for motion and 33
      under stress. The range of motion was 79% of the opposite side for
      extension/flexion and 83% for radial/ulnar deviation. The average DASH-score
      reached 15 points. The Herbert mini screw has proven to be a reliable implant for
      reconstruction of proximal pole fractures and nonunions of the scaphoid.

PMID- 11572123
TI  - [Femoral neck fracture in the younger patient. Contrast between guideline and
      management reality--results of external quality assurance in 1,747 follow-up
      cases].
AB  - Between January 1993 and December 1998 26.005 patients with hip fractures
      underwent treatment in departments of general surgery and traumatology in
      Westfalia-Lippe, Germany. Data of these patients were reported to the chamber of
      physicians where a report card system for external quality assurance has been
      established since 1991. 1.747 patients were between 10 and 60 years of age.
      Treatment according to the guideline of hip fractures of the German College of
      Traumatology is compared to treatment in reality. RESULTS: Conservative treatment
      declined to 2% in 1998; only 43% of these comparetively young patients were
      labeled as emergencies. Only 45.4% of all osteosyntheses were performed on the
      day of hospital admission. Almost 30% of the patients undergo hip replacement as
      first line therapy. Timing of operation is related to the frequency of operations
      per department and specialisation: the more operations per year the shorter the
      length of stay before operation. Early treatment is more likely in departments of
      traumatology than in departments of general surgery. Lethality and morbidity do
      not increase with early treatment. CONCLUSIONS: The reality of treatment of hip
      fractures does not meet the criteria of the guideline. Further efforts have to be
      undertaken for the benefit of relatively young patients with hip fractures.

PMID- 11572124
TI  - [Introduction of a new mobile C-arm/CT combination equipment (ISO-C-3D). Initial
      results of 3-D sectional imaging].
AB  - Preclinical evaluation of a new mobile C-arm image amplifier with an option for
      three-dimensional computed tomography (CT) imaging (prototype Iso-C3D) with
      respect to high-contrast resolution and possible clinical applications. Cadaveric
      specimens (n = 30) of different joints of the lower and upper extremities and
      specimens of the spinal column were examined with the Iso-C3D and evaluated for
      image quality. In addition, using a high-contrast phantom (Catphan, Phantom
      Laboratory, Salem, N.Y., USA) and a fracture model of the femoral bone,
      measurements of high-contrast resolution were performed in comparison to spiral
      CT. With the exception of the shoulder, all joint regions including the entire
      spinal column could be examined. Adequate image quality could be achieved in
      smaller joints such as the wrist, elbow, ankle, and knee, whereas a remarkably
      decreased image quality was found when imaging the hip as well as the lumbar and
      thoracic spine. Images of the phantom study and high-contrast fracture model
      showed a high-contrast resolution comparable to helical CT (9 Lp/cm in xy-axis).
      In smaller joints, the image quality of the mobile C-arm CT imaging system (Iso
      C3D) is comparable to that of helical CT. Image quality in examinations of the
      hip and lumbar and thoracic spine seems to be sufficient for intraoperative
      control studies of osteosynthesis. Problems still occur in shoulder examinations.

PMID- 11572125
TI  - [3-D imaging with a mobile surgical image enhancement equipment (ISO-C-3D).
      Initial examples of fracture diagnosis of peripheral joints in comparison with
      spiral CT and conventional radiography].
AB  - To analyze a prototype mobile C-arm image amplifier (Iso-C3D) in the evaluation
      of different joint fractures of the upper and lower limbs using multiplanar
      reconstruction (MPR). Different cadaver joint specimens (n = 14) were examined
      with a prototype (Iso-C3D, Siemens AG, Erlangen, Germany), plain radiographs
      (CR), and spiral computed tomography (CT). The motorized C-arm provides
      fluoroscopic images during a 190 degrees orbital rotation computing a 119-mm data
      cube. These three-dimensional data sets yielded MPR images, which were evaluated
      by two readers for the detection and extent of fracture lines. Initial data show
      that fractures were easily depicted and correctly classified on MPR images with
      the Iso-C3D and that there was no difference between the Iso-C and CT in the
      detection of fractures. The preliminary results suggest a remarkably good
      detection of joint fractures with the Iso-C3D. Studies in an adequate number of
      patients are required to elucidate whether these promising results can also be
      obtained in a clinical setting.

PMID- 11572126
TI  - [Comparative study of the quality of C-arm based 3D imaging of the talus].
AB  - Malposition of extraosseous or intra-articular screws, e.g., in osteosyntheses of
      joint fractures or in the vicinity of joints, frequently remains undiscovered in
      intraoperative fluoroscopy and is only recognized on postoperative computed
      tomography (CT) scans. The aim of the study, therefore, was to assess the value
      of a new mobile C-arm three-dimensional imaging device in comparison with
      fluoroscopy, conventional radiographs, and CT scans using an extremity model.
      Screws were inserted ventrally in four anatomic lower leg specimens without talus
      fractures parallel to the longitudinal axis to simulate surgical management of
      fractures of the talus. The specimens supplied were examined with fluorscopy,
      conventional radiography, spiral CT, and the new three-dimensional imaging with
      the SIREMOBIL Iso-C3D. These four modalities were evaluated by ten radiologists
      and ten trauma surgeons and were compared regarding subjective image quality and
      position of the screws. The quality of information acquired with the SIREMOBIL
      Iso-C3D was equal to that of the CT examinations, although image quality was
      considered inferior to fluoroscopy, conventional radiography, and CT (p < 0.001).
      In contrast to the previous procedure with intraoperative fluoroscopy and
      subsequent postoperative X-ray control, the results obtained with the SIREMOBIL
      IsoC3D were superior. The SIREMOBIL Iso-C3D is useful for the intraoperative
      diagnosis of small joints with few artifacts producing osteosynthesis material,
      i.e., for recognizing the position of screws in the region of glenoid surfaces.

PMID- 11572127
TI  - [Long-term results after excision of a popliteal cyst].
AB  - The objective was to evaluate long term results after removal of a popliteal cyst
      with special focus on recurrence rate and associated intraarticular pathology.
      Between 1982 and 1995 71 patients (23 women and 48 men between 21 and 75 years of
      age) underwent removal of a popliteal cyst. An additional arthroscopy of the knee
      joint was carried out in 51 consecutive patients starting in 1988. The mean
      follow up was 6.5 years (2 to 15 years), 66 patients (93%) were available. The
      subjective satisfaction with the outcome was assessed using a visual analogue
      scale (VAS) graded from 1 (highly satisfied) to 10 (highly dissatisfied). The
      popliteal region was evaluated by ultrasonography for recurrence of a cyst.
      During arthroscopy the predominant associated intraarticular pathologic finding
      was the lesion of the posterior horn of the medial meniscus (75%) and the lesion
      of the hyaline cartilage (90%). The cyst recurrence rate was 71%. In this
      subgroup grade III and grade IV chondral lesions were significantly more frequent
      (p < 0.001). Patients with a recurrence of the popliteal cyst rated the result
      significantly worse (7.6 +/- 2.3 vs. 3.4 +/- 2.3; p < 0.001). The recurrence rate
      was relatively high in the long term follow up. It depends strongly on the type
      of associated intraarticular pathology. Especially grade III and grade IV
      chondral lesions correlated significantly with recurrence of a popliteal cyst
      after removal. Therefore, the main goal of surgery should be the successful
      treatment of associated intraarticular pathologies.

PMID- 11572128
TI  - [Crossed screw osteosynthesis of proximal humerus fractures].
AB  - Between March 1997 and October 1999 thirty-one patients with displaced proximal
      humeral fractures were treated with crossed screw osteosynthesis. Insertion of
      the screws was realized by using a deltoideo-pectoral approach placing the screws
      anteriorly and posteriorly in a crossed manner from the distal fragment into the
      humeral head. Additionally, in all two-part-fractures a tension band was applied.
      In all three-part-fractures, the greater tuberosity was reattached by additional
      screws. In 21 patients (14 female, 7 male, median age 62 years, 18-86) a clinical
      and radiological follow-up (median 18 months, 10-29) was obtained. Fractures were
      classified as two-part-fractures in 10 patients and as three-part-fractures in 11
      patients. According to the Constant-Score, "excellent" and "good" results were
      achieved in 15 patients, "moderate" results were found in 3 patients. However, in
      3 patients results were only "poor" (1 two-part-, 2 three-part-fractures). The
      complication rate was 29% (premature hardware removal due to head perforation in
      3 cases; humeral head necrosis necessitating prosthetic replacement in 2
      patients; secondary displacement in 1 case). Crossed screw osteosynthesis
      represents an justified alternative in the surgical treatment of displaced
      proximal humeral fractures permitting early functional therapy.

PMID- 11572129
TI  - [Abdominal trauma].

PMID- 11572130
TI  - [Fracture of the acromion. Diagnosis--treatment strategy--outcome].
AB  - The case of an 22-year-old man is presented, who sustained a dislocated fracture
      of the left acromion process and a not dislocated fracture of the left scapular
      body with a large subcutaneous decollement as well as a dammage of nervus
      axillaris occurring during a traffic accident. After resuming diagnostics by
      means of CT, a tension banding of the ventral part of the acromion and a plate
      osteosynthesis of the dorsal part was performed. 7 weeks after injury neurolysis
      of nervus axillaris has been done. 4 months after accident the patient shows a
      satisfying functional result in the Constant score. Diagnostic, treatment and
      functional results after operative treatment of dislocated fractures of the
      acromion are shown and discussed.

PMID- 11572131
TI  - [Spinal epidural hematoma as a sequelae of knife stab injury. A diagnostic
      problem?].
AB  - Spinal epidural hematoma are a rare but serious complication of thoracic stab
      wounds. Their incidence should always be taken into consideration when first
      examining the patient, and it is also necessary to be able to find proof in
      either MRI or CT-scan. In our case the patients diffuse neurologic symptoms
      connected with a rather unreliable appearing personality made the diagnosis even
      more difficult. Initially it was possible to show the defect only in MRI.

PMID- 11572132
TI  - [Peri-articular calcinosis. Tumor simulating calcinosis and differential
      diagnosis].
AB  - The disease of tumorous calcinosis is presented in order to one case and a survey
      of literature. The epidemiology and etiology are discussed, because of a rare
      manifestation of metabolic disorders. The differential diagnosis includes genetic
      disorders, recurrent soft-tissue trauma and renal failure. The clinical symptoms
      like swelling or deficit of function as well as radiologic appearances may lead
      to the diagnosis. The way of treatment is given by radical excision and metabolic
      supervision. The multiloculated presentation of periarticular, dental,
      subcutaneous and other lesions is pointed out.

PMID- 11572133
TI  - [Surgical therapy of traumatic shoulder dislocation. Are there evidence-based
      indications for arthroscopic Bankart operation?].
AB  - INTRODUCTION: For young athletic patients with a primary traumatic shoulder
      dislocation a surgical treatment is recommended. The operation of choice is the
      Bankart-Repair. QUESTION: Are there evidence-based indications for an
      arthroscopic Bankart repair. METHODS: Based on the criteria of the "Cochrane
      Collaboration" a systematic literature search was performed using medline (1966
      to 9/2000). 172 publications were found with the key words "shoulder dislocation"
      and "Bankart". All relevant articles were ranked and analysed by the criteria of
      "evidence-based medicine". RESULTS: There are 12 prospective studies (evidence
      grade Ib/IIa) and another 28 retrospective studies (evidence grade III). For open
      Bankart-Repair a recurrence rate of 0 to 8% is reported
      (prospective/retrospective studies). For arthroscopic Bankart-Repair, 19 of 40
      studies and 8 of 12 prospective studies, show a recurrence rate of < 10%; however
      in other studies (prospective/retrospective) an atraumatic recurrence rate of up
      to 38% is reported. The reasons for these differences in the recurrence rate are
      not obvious from the given data. In particular, there seems to be no correlation
      between the type of arthroscopic fixation technique and the recurrence rate.
      Concerning the postoperative range of shoulder motion, the reported data suggest
      that external rotation is less limited after arthroscopic than after open Bankart
      Repair (arthroscopic: 5-12 degrees, open: 5-25 degrees). However, there is no
      evidence that patients are more likely to return to their previous level of
      sporting activities when operated on in an arthroscopic technique than in an open
      technique (arthroscopic: 42-100%, open: 72-94%). CONCLUSION: In the surgical
      treatment of a traumatic shoulder dislocation, the open Bankart-Repair remains
      the "gold standard". In reviewing the literature, arthroscopic Bankart-Repair has
      not been shown to be equal or superior to the open technique.

PMID- 11572134
TI  - [Research sabbatical of German physicians in foreign countries].

PMID- 11572135
TI  - Recent challenges in infectious diseases. Biological pathogens as weapons and
      emerging endemic threats.
AB  - This article reviews emerging and re-emerging infectious diseases and provides
      insights regarding the evolution of our understanding of natural diseases and how
      that knowledge impacts the development of plans and methods for defending against
      the deliberate use of biological agents. Also discussed are forensic and legal
      issues for the pathologist concerning agents of biological terrorism and
      biological warfare, the concept of chain of custody, transport, storage, and
      biosafety levels. It defines the importance of the pathologist in managing the
      threat posed by biological weapons.

PMID- 11572136
TI  - History of the development and use of biological weapons.
AB  - The United States began its BW program based on intelligence information and a
      very thorough evaluation of that information by a panel of scientists, engineers,
      medical personnel from a variety of areas including the military, other
      government agencies, industry, and the academic community. Initial efforts were
      directed toward defense against BW, but it soon became clear defense required a
      knowledge of offensive capabilities. The initial offensive studies started with a
      definition of what infectious organisms were available, how they could grow in
      quantities to support a munitions program, what kind of facilities were required,
      and where they could be positioned. Further studies were then initiated to design
      and evaluate testing sites and methodologies to evaluate the weapons. During all
      of these phases, concurrent medical and safety programs were studied, emphasized,
      and implemented. These studies resulted in the development of a number of
      vaccines, toxoids, treatments, therapies, and facility personnel management. The
      US program had one of the lowest, if not the lowest, personnel lost time because
      of personnel infections. The overall conclusion was that BW, offensive and
      defensive, was possible, and efficiencies could be obtained. The work
      accomplished by this group of very dedicated military and civilian personnel at
      military installations, universities, research institutes, and industrial
      organizations presented truly a combined operation with numerous achievements.
      Many of the detailed achievements were published in the open scientific, peer
      reviewed journals, and many patents were obtained. The current defensive program
      is breaking new scientific ground and there is evidence indicating that very
      rapid detection and identification of BW agents is possible and will be
      instrumented.

PMID- 11572137
TI  - Clinical recognition and management of patients exposed to biological warfare
      agents.
AB  - Concern regarding the use of biological agents (bacteria, viruses, or toxins) as
      tools of warfare or terrorism has led to measures to deter their use or, failing
      that, to deal with the consequences. Unlike chemical agents, which typically lead
      to severe disease syndromes within minutes at the site of exposure, diseases
      resulting from biological agents have incubation periods of days. Rather than a
      paramedic, it will likely be a physician who is first faced with evidence of the
      results of a biological attack. Provided here is an updated primer on 11 classic
      BW and potential terrorist agents to increase the likelihood of their being
      considered in a differential diagnosis. Although the resultant diseases are
      rarely seen in many countries today, accepted diagnostic and epidemiologic
      principles apply; if the cause is identified quickly, appropriate therapy can be
      initiated and the impact of a terrorist attack greatly reduced.

PMID- 11572138
TI  - Clinicopathologic features of viral agents of potential use by bioterrorists.
AB  - Concerns regarding the possible use of viral agents as weapons of mass
      destruction have heightened our need to recognize disease syndromes caused by
      these pathogens and to increase our understanding of potential countermeasures.
      This article reviews the clinical and pathologic features of various viruses that
      are generally thought to be potential biowarfare threats, and other related
      agents of topical interest. The epidemiologic and clinical aspects of recent
      natural outbreaks of disease caused by exotic viral agents are briefly described.
      Viral tissue targets, immune responses to these agents, relevant animal models,
      and diagnostic and potential therapeutic modalities also are discussed.

PMID- 11572139
TI  - The laboratory role in diagnosis of infections transmitted by arthropods.
AB  - This article provides an overview of arbovirus diseases from the perspective of
      laboratory diagnosis and related responsibilities of health personnel. Although
      the disease manifestations are very diverse, general lessons relevant to optimal
      use of laboratory resources can be drawn from medically important examples. This
      approach is warranted, because under conditions of bioterrorism or emergence of a
      novel pathogen, ecologic clues that ordinarily facilitate identification of an
      arbovirus infection most likely will be absent.

PMID- 11572140
TI  - Clinicopathologic aspects of bacterial agents.
AB  - Bacteria were the first organisms recognized for their potential as agents of
      bioaggression and the possibility of their use by a terrorist or rogue nation is
      considered a significant threat. Five of the more likely agents (anthrax, plague,
      tularemia, Q fever, and brucellosis) are reviewed with emphasis on their
      epidemiology, clinical presentation, diagnosis, and pathology. Particular
      emphasis is given to the presentation of the diseases as they may appear after
      use in a biowarfare scenario.

PMID- 11572141
TI  - Agroterrorism, biological crimes, and biowarfare targeting animal agriculture.
      The clinical, pathologic, diagnostic, and epidemiologic features of some
      important animal diseases.
AB  - In the past 100 years, to our knowledge there have been approximately 12 events
      involving the intentional introduction of microbiologic agents into livestock and
      animal populations worldwide, of which three were World War I events in the
      United States. To the best of the authors' knowledge, there has been no recent
      intentional introduction of microbiologic agents (viruses or bacteria) into
      livestock and animal populations in the United States. The criminal or terrorist
      use of chemicals against animals and agriculture products have been more common.
      With the political, economic, and military new world order, however, the United
      States must maintain a vigilant posture. The framework for this vigilance must be
      an intelligence system sensitive to the needs of agriculture and a first-class
      animal disease diagnostic surveillance and response system.

PMID- 11572142
TI  - Bioregulators as instruments of terror.
AB  - Bioregulators are naturally occurring organic compounds that regulate diverse
      cellular processes. Unlike traditional disease-causing biowarfare agents that
      take hours or days to act, many bioregulators act within minutes of
      administration. If exploited for the purpose of bioterrorism, they could
      potentially cause profound physiologic effects. Other effects may be more subtle.
      The main groups of bioregulators discussed are cytokines; eicosanoids,
      neurotransmitters, hormones, and proteolytic enzymes. Because advances
      continually are being made in their development, bioregulators should be
      considered as weapons with increasing bioterrorism potential.

PMID- 11572143
TI  - The emerging impact of genomics on the development of biological weapons. Threats
      and benefits posed by engineered extremophiles.
AB  - During the past decades, representatives of Archaea, Bacteria, and Protista have
      been found thriving in many newly discovered extremely hostile habitats, which
      hitherto were regarded as too harsh to harbor life. To illustrate how an
      extremophile could be targeted for development as a biowarfare agent, an example
      is presented describing current advances in engineering Deinococcus radiodurans.
      Using a generally applicable combination of conventional genetic engineering and
      genomic informatics, this extremely radiation-resistant and environmentally
      robust bacterium is being developed for biotechnology.

PMID- 11572144
TI  - Applying molecular biological techniques to detecting biological agents.
AB  - Recent efforts in the civilian and military health care and public health
      communities are directed at strengthening surveillance systems and our national
      laboratory capabilities for early detection of infectious disease outbreaks.
      These new systems will address proper specimen collection, transport, nucleic
      acid processing, molecular assay diagnostic reagent and equipment development,
      and standardization for sensitive and rapid detection of bioagents in blood and
      other clinical samples. A greater understanding of the genetic diversity and
      virulence factors for each organism that could be used for bioterrorism would aid
      design of rapid molecular detection strategies. Combinations of appropriate
      diagnostic technologies (culture, immunoassay, and molecular assay) can provide
      rapid diagnostic response capabilities to microbial threats with antimicrobial
      resistant organisms, new emerging infectious disease agents, and possible agents
      of bioterrorism.

PMID- 11572145
TI  - Current laboratory methods for biological threat agent identification.
AB  - The authors present an integrated approach for the identification of biological
      threat agents. The methods used have been used extensively in field exercises and
      during response to incidents of biological terrorism. A diagnostic system, which
      integrates the clinical diagnosis or medical intelligence with immunodiagnostic
      tests, rapid gene amplification assays, and standard culture, provides results of
      the highest quality and confidence. In the future, selected reagents and
      technologies will be distributed through a network of civilian and military
      laboratories.

PMID- 11572146
TI  - Advances in medical biological defense technology.
AB  - No single medical countermeasure will meet the needs for defense against all
      biological threats in all possible scenarios (civilian, military, clinical, and
      environmental). As the threat of genetically engineered organisms rises and the
      risk increases that these organisms might escape detection and successful
      treatment, it will be necessary to use advances in bioengineering to combat these
      new threats. This article presents several novel approaches taken by the DoD in
      collaboration with industry partners and other federal laboratories to produce
      improved biowarfare vaccines, diagnostics, and treatments. In the future, the
      United States must remain on the cutting edge of biotechnology and continue to
      predict the next areas of research necessary to maintain protection for the state
      of-the-art warfighter on the battlefield.

PMID- 11572147
TI  - Residual HIV-1 persistence during suppressive HAART.

PMID- 11572148
TI  - Is anything safe to eat?

PMID- 11572149
TI  - Management of severe candidal infections: integration and review of current
      guidelines for treatment and prevention.

PMID- 11572150
TI  - New insights into the pathogenesis and therapy of sepsis and septic shock.

PMID- 11572151
TI  - Laboratory response to the challenge of today's medical care environment--using
      the laboratory cost-effectively to enhance patient care.

PMID- 11572152
TI  - Magnetic resonance imaging of bone and soft tissue infections.

PMID- 11572153
TI  - Quinupristin/dalfopristin and linezolid: spectrum of activity and potential roles
      in therapy--a status report.

PMID- 11572154
TI  - Pathogenesis, prevention, and therapy of staphylococcal prosthetic infections.

PMID- 11572155
TI  - Antiviral agents effective against herpesviruses.

PMID- 11572156
TI  - Clinical use of granulocyte colony-stimulating factor in infectious diseases.

PMID- 11572157
TI  - Acute sinusitis: current status of etiologies, diagnosis, and treatment.

PMID- 11572158
TI  - Diagnostic molecular microbiology.

PMID- 11572159
TI  - Vaccines for Lyme disease.

PMID- 11572160
TI  - Genomics technologies and strategies for identification of novel anti-infective
      agents.

PMID- 11572161
TI  - Cost-benefit and effectiveness of nosocomial surveillance methods.

PMID- 11572162
TI  - Current status of opportunistic infections in patients with HIV infection in the
      era of highly active antiretroviral therapy.

PMID- 11572163
TI  - Malaria: epidemiology, pathogenesis, diagnosis, prevention, and treatment--an
      update.

PMID- 11572164
TI  - [The endless dry weight quest].

PMID- 11572165
TI  - [Ionic dialysance and quality control in hemodialysis].
AB  - Quantification of dialysis is based on the measurement of effective urea
      clearance (K), dialysis dose (Kt) or normalized dialysis dose (Kt/V). During the
      last 20 years, Kt/V was the single parameter actually useful for quantifying
      dialysis efficiency, because it can be calculated from just blood or dialysate
      urea concentrations at the beginning and at the end of the dialysis session.
      However the calculation of the normalized dialysis dose (Kt/V) actually delivered
      to the patient cannot be performed during each dialysis session, because of the
      need of urea concentration measurements. Ionic dialysance is a new parameter
      easily measured on-line, non-invasively, automatically and without any cost
      during each dialysis session by a conductivity method. Because ionic dialysance
      has been proved equal to the effective urea clearance taking into account
      cardiopulmonary and access recirculation, it is becoming an actual quality
      assurance parameter of the dialysis efficiency.

PMID- 11572166
TI  - [Contribution of clinical epidemiology to evidence-based nephrology].
AB  - Improvement of modern medicine does not make day-to-day practice of nephrology
      easier. Decision-making remains difficult, often requiring numerical,
      probabilistic approach. Contribution of clinical epidemiology to evidence-based
      nephrology is not limited to randomised-controlled trial. The concept of natural
      history: spontaneous evolution without treatment, has been developed in
      epidemiology to describe diagnosis and prognosis of diseases. For example, in IgA
      nephropathy, it allowed to measure the prognostic significance of gross hematuria
      or to design classification of end-stage renal failure. Epidemiologic studies
      needs appropriate designs, representative samples and correct methods of
      analysis. Like other medical research, epidemiology has some important
      methodological limits that must be taking into account. Practising evidence-based
      nephrology improves confidence in management decisions.

PMID- 11572167
TI  - [Sinusitis as a major cause of fever in intubated patients].
AB  - Because sinusitis is usually clinically silent in intubated patients, it is not
      widely appreciated as an important source of infection and fever in critically
      ill patients. Three such patients, two men aged 22 and 36 years, and a woman aged
      50 years, suffered from respiratory insufficiency due to pneumonia. The course of
      the disease was determined by the sinusitis, which did not resolve during
      antibiotic therapy of the pneumonia, notwithstanding the fact that the causative
      micro-organism was susceptible to the antibiotics administered, and that both the
      tracheal and gastric tubes were led through the mouth instead of the nose.
      Flushing of the sinuses caused the fever to disappear and led to recovery of the
      patients. An aggressive approach to diagnose sinusitis in the intubated patient
      with fever in the intensive care unit is needed. A maxillary sinus lavage and
      culture, followed by treatment with specific antibiotics should be an integral
      part of the diagnosis and treatment in these patients. Surgery is indicated in
      the event of persistent sepsis.

PMID- 11572168
TI  - [Meningococcal disease in the Netherlands: media hype, but not an epidemic].
AB  - An outbreak of meningococcal disease caused by Neisseria meningitidis C, type 2a
      recently occurred in the Dutch province of West-Brabant. Five children were
      affected and two of these died. The Outbreak Management Team decided to start a
      local vaccination campaign with a meningococcal group C conjugate vaccine. The
      publicity surrounding these cases of meningococcal disease led to much anxiety
      throughout the Netherlands. Despite parent's concerns, there is nothing to
      indicate the presence of an epidemic.

PMID- 11572170
TI  - [State of the Dutch health care: need for more refined and specific indicators].
AB  - The 'World health report 2000' follows a trend towards the use of performance
      indicators in public services. The indicators used by WHO are in need of
      conceptual refinement and valid measurement, especially the more subjective ones.
      The use of indicators for final goals of health (care) systems makes it difficult
      to translate lack of performance into policy. Instrumental goals are also needed
      for the latter. It is concluded that the overall performance of the Dutch health
      care system is built up of the performance of its individual sections. The
      concrete areas for improvement within these sections need to be identified, while
      at the same time a performance paradox should be avoided.

PMID- 11572169
TI  - [Adjuvant therapies for sepsis and shock: which are more effective?].
AB  - Adjuvant therapy for severe sepsis and shock can be divided into 4 groups. The
      first group comprises those compounds with proven efficacy in human studies
      (activated protein C and recombinant bacterial permeability-increasing protein).
      The second group includes compounds with potential efficacy (heparin), while the
      third group represents those with no demonstrated efficacy in randomised clinical
      trials (tumour necrosis factor and interleukin-1 antibodies and receptor
      antagonists). The fourth group includes those drugs which have been found to be
      potentially effective in animal studies, but which have not yet been evaluated in
      humans (i.e., tyrosine kinase inhibitors, selective inducible nitric oxide
      synthase inhibitors, polyadenosine-diphosphate-ribose-polymerase and caspase III
      (apoptosis) inhibitors). Formal clinical comparisons between the various
      treatment options are necessary to assist the clinician in selecting the
      appropriate form of therapy.

PMID- 11572171
TI  - [Corticosteroid administration for critically ill patients].
AB  - In critically ill patients, the hypothalamic-pituitary-adrenal axis is usually
      activated, resulting in elevated plasma cortisol levels. This enables the human
      organism to cope with sepsis, trauma and other forms of stress. During critical
      illness, total adrenal insufficiency rarely occurs. On the other hand, septic
      shock can be accompanied by a relative deficit of cortisol. Causes of this
      relative adrenal insufficiency are a dysfunction of the hypothalamic-pituitary
      adrenal axis and/or cortisol resistance. There are no strict biochemical criteria
      available to diagnose relative adrenal insufficiency; clinical observation is the
      decisive factor. In randomised trials with patients in septic shock, a more rapid
      haemodynamic recovery was obtained with physiological doses of hydrocortisone
      than with a placebo. The observed haemodynamic response following hydrocortisone
      administration supports the concept of relative adrenal insufficiency.

PMID- 11572173
TI  - [Diagnostic image (54). Sinus thrombosis and hemorrhagic infarction in puerperium
      ].
AB  - A 28-year-old woman developed puerperal sinus sagittalis superior thrombosis that
      caused hemorrhagic cerebral infarction and death by cerebral herniation.

PMID- 11572172
TI  - [Neuromodulation and neurostimulation in urology].
AB  - Functional voiding disorders, such as urge incontinence and urine retention, have
      a high prevalence and often lead to stigmatisation and a diminished quality of
      life. Patients with idiopathic voiding dysfunctions, for whom conservative
      treatments are insufficient, can currently be treated with sacral
      neuromodulation. In sacral neuromodulation a pulse generator is implanted; it is
      a reversible treatment that can be tested beforehand to evaluate if the patient
      is eligible for it. After implantation a good result is obtained, on average, in
      73% of patients. Patients with spinal cord injury may currently be treated with
      electrical neurostimulation of the anterior sacral roots, which results in the
      ability to void without a residue, evacuate stools and obtain an erection or
      vaginal lubrication. Over 80% of the implanted patients with a spinal cord injury
      void without residual urine. Furthermore, continence is restored and the bladder
      capacity increases. In patients with therapy-resistant functional micturition
      disorders and in patients with spinal cord injury, neuromodulation and
      neurostimulation must be considered before invasive surgery is carried out.

PMID- 11572174
TI  - [From gene to disease; neurofibromatosis type 1].
AB  - Neurofibromatosis type 1 (NF1) is an autosomal dominant disease characterised by
      cafe-au-lait spots, freckling in the axillary or inguinal region, dermal and
      plexiform neurofibromas and Lisch nodules. Complications are severe in one third
      of patients, and the clinical variability is pronounced, even within families.
      The NF1 gene has been localised to chromosome 17q11.2 and encodes the protein
      neurofibromin. The gene is proposed to be a tumour suppressor gene. Inactivation
      of neurofibromin leads to a disruption in cell growth regulation. Mutation
      analysis is possible but laborious, and therefore NF1 is generally a clinical
      diagnosis based on diagnostic criteria.

PMID- 11572176
TI  - [Frequency of duodenal adenomas in patients with familial adenomatous polyposis].
AB  - OBJECTIVE: To estimate the prevalence of polyps in the stomach and duodenum in
      patients with familial adenomatous polyposis (FAP), and to examine the
      relationship between age and severity of duodenal adenomatosis. DESIGN:
      Retrospective. METHOD: Using the FAP-registry of the Netherlands Foundation for
      the Detection of Hereditary Tumours, data were obtained from patients who had
      undergone a gastroduodenoscopy before 1 July 1999. The endoscopic and
      histological findings were used to classify the duodenal adenomas according to
      the Spigelman classification. RESULTS: 224 patients had undergone at least one
      gastroduodenoscopy: 117 men and 107 women with a mean age at the time of the
      first endoscopy of 37 years (range: 13-78). Fundic gland polyposis was detected
      in 79 patients (35%), stomach adenomas in 6 patients (3%) and duodenal adenomas
      in 92 patients (41%). A total of 21 patients (9%) had severe duodenal
      adenomatosis (Spigelman III or IV). Duodenal adenomatosis was often more severe
      if the patient was older. Ten patients were known to have duodenal cancer; the
      mean age at diagnosis was 50.3 years (range: 39-67). CONCLUSION: Nearly 10% of
      the patients with FAP had developed severe duodenal adenomatosis. The severity of
      duodenal adenomatosis was related to the patient's age.

PMID- 11572178
TI  - [Misleading advertisement of Adalat Oros].
AB  - Referring to the INSIGHT trial published in The Lancet, Bayer Netherlands states
      in an advertisement in Dutch medical journals that nifedipine reduces
      cardiovascular events by 50% in patients with hypertension and at least one
      additional risk factor. However, the agent studied in the INSIGHT trial did not
      reduce cardiovascular events in comparison to treatment with a diuretic. On the
      contrary, the incidence of myocardial infarction increased (fatal infarction even
      increased significantly), and the risk of stroke was not significantly reduced.
      Therefore the advertisement is misleading.

PMID- 11572177
TI  - [Relative adrenocortical insufficiency with sepsis, diagnosed and treated with
      hydrocortisone supplementation].
AB  - An 82-year-old woman was admitted to the ICU with septic shock and multiple organ
      failure. Despite the lack of a persistent septic focus she continued to be
      dependent on large doses of norepinephrine whilst receiving adequate
      antimicrobial therapy. After a trial treatment with hydrocortisone the
      norepinephrine infusion could be withdrawn within a few days and she made a full
      recovery. In the case of seriously ill patients the diagnosis 'relative
      adrenocortical insufficiency' is predominantly made on the basis of the clinical
      picture. The remarkable clinical response to the administration of hydrocortisone
      (400 mg in the first 24 h) confirmed the diagnosis. The dosage of vasopressors
      can be reduced remarkably quickly. The stimulatory test for adrenocorticotropin
      hormone (ACTH) has no added value as reference values for critically ill patients
      are not available and because the results do not predict the response to the
      treatment.

PMID- 11572179
TI  - [Performance of the Dutch health care from an international perspective:
      background and implications for policy].
AB  - The 'World Health Report 2000' has stimulated discussions on the Netherlands'
      performance in health and healthcare from an international perspective. The only
      concrete result it provided was a world ranking in which the Netherlands stood in
      17th place. The comparative data which have appeared in several other recent
      reports, are more useful to policy makers, a notable example being those from the
      Organization for Economic Cooperation and Development (OECD). One issue arising
      from these reports is that the increase in life expectancy in the Netherlands is
      lagging behind the European Union average. This is particularly the case for
      women and a major cause of this is smoking. Developments in Dutch perinatal
      mortality are also unfavourable and are associated with a strong increase in the
      age at which women bear children. International comparisons of public health data
      are valuable inputs for health policy development and it is therefore important
      to invest in the international harmonisation of such data collection.

PMID- 11572180
TI  - [Report of the Dutch Health Council on the cost-effectiveness of long-term
      psychotherapy].

PMID- 11572181
TI  - [Doctors are increasingly held liable for missed diagnosis of cancer in mass
      screening].

PMID- 11572182
TI  - [Diarrhea due to a toxin of Clostridium difficile in hemato-oncological
      patients].

PMID- 11572183
TI  - [Prevention of occlusions after infra-inguinal bypass surgery with oral
      anticoagulants or acetylsalicylic acid; a randomized comparison].

PMID- 11572184
TI  - [Tamoxifen; wider indications, more frequent controls?].

PMID- 11572185
TI  - The central loop of H-reflex in the S1 spinal nerve: normal values and
      constitutional influencing factors.
AB  - OBJECTIVE: To investigate the central loop of H reflex in the S1 nerve and the
      constitutional influencing factors in normal healthy individuals. MATERIALS AND
      METHODS: The study was performed on 39 apparently healthy volunteers. To obtain
      central H-reflex, the cathode electrode was inserted at a point 1 cm medial to
      the posterior superior iliac spine, perpendicular to the frontal plane. After the
      needle touched the sacrum, it was slightly retracted to avoid direct contract to
      the sacrum. The anode electrode was placed over the anterior iliac spine. The
      active pick-up electrode was placed at the middle of the line connecting the
      popliteal crease to the medial malleolus. The reference electrode was placed 2 cm
      distal to it. The ground eletrode was placed near the active pick-up electrode
      over the calf muscles. RESULTS: Mean +/- SD for minimum necessary stimulation to
      obtain central H-reflex was 23 +/- 13 mA. This was significantly higher than the
      minimum necessary stimulation to obtain peripheral H reflex (p < 0.0001 using
      paired t test). Mean central loop of H reflex was 6.9 msec with SD of 0.4 msec.
      There were no significant differences between the two sides. Mean amplitude of M
      wave was 2.2 mV with SD of 1.5 in central loop study. Mean amplitude of H-wave
      was 2.4 mV with SD of 1.5 in central loop study. The Mean time interval between
      the onset of M-wave and the end of H-wave (M-H duration) was 18.5 msec with SD of
      2.3. After stepwise reduction of variables, considering the correlation between
      leg length and other variables, the leg length was the only variable strongly
      correlating with central loop of H-reflex. CONCLUSION: Lack of major influencing
      factors after correction for leg length, elimination of a major fraction of the
      afferent segment of the loop, and its ability to differentiate peripheral from
      central lesions make central H-reflex studies an invaluable diagnostic tool.

PMID- 11572186
TI  - Electromyographic validation of the trapezius and serratus anterior muscles in
      military press exercises with middle grip.
AB  - Electromyographic activity of the trapezius muscle and serratus anterior muscle
      was analysed in 24 male volunteers using a 2-channel TECA TE 4 electromyograp,
      during the execution of four different modalities of military press exercises
      with middle grip. The trapezius acted preferentially in the modalities standing
      press behind neck; and sitting forward and press behind neck, while SI did not
      show any significative difference among the modalities. The high levels of action
      potentials with which TS and SI acted justify the inclusion of these exercises in
      physical programmes.

PMID- 11572187
TI  - The changes in the transmission functioning of the ulnar nerve in a high power
      magnetic field.
AB  - INTRODUCTION: The present study aims at exploring the changes in the functioning
      of the ulnar nerve in a high power magnetic field. METHODS: 12 volunteers with a
      healthy peripheral nervous system participated in the study. The ulnar nerve was
      selected from the upper organs as the site for study. The functioning of both the
      sensory and motor parts of the ulnar nerve in normal conditions was
      electromyographically tested. Then, using the same setting, the functioning of
      the nerve was electromyographically tested within a high power magnetic field
      (0.2 Tesla). With regard to the sensory function, the distal latency and the
      amplitude were examined. With regard to the motor section, the duration,
      amplitude of the evoked potentials, and latency from two sites--distal and
      proximal--were examined. These results of the two readings, taken in normal
      condition and in a high power magnetic field, as well as the motor neural
      conduction velocity, were compared. RESULTS: The statistical analyses indicated
      that the changes in both the distal latency and amplitude of the sensory part of
      the ulnar nerve were significant. However, the changes in the motor function of
      the nerve were not significant.

PMID- 11572188
TI  - F wave parameters and F tacheodispersion in mild diabetic neuropathy.
AB  - F tacheodispersion and some F wave parameters have previously been suggested to
      be useful in the detection of peripheral nerve involvement in diabetic patients
      with normal nerve conduction studies. In this study, ulnar and tibial F wave
      parameters of diabetic cases with normal motor and sensory nerve conduction
      studies (Group 1) were calculated, F tacheodispersion histograms were constructed
      and compared with the same parameters obtained from the normal controls (Control
      group) and diabetic cases with abnormal motor and sensory nerve conduction
      examinations (Group 2). There was a tendency towards lower conduction velocities
      in ulnar and tibial tacheodispersion histograms of Group 1 and Group 2, as
      compared to Control group. Most of the F wave values were significantly abnormal
      in Group 2 in comparison to other two groups, whereas statistically significant
      differences between Group 1 cases and Control group were found in minimum ulnar F
      wave conduction velocity (FCVmin), mean ulnar FCV (FCVmean), tibial FCVmin and
      tibial FCVmean values. Unlike other methods, F waves give information about the
      entire length of the motor nerve fiber. In mild neuropathies, in which nerve
      fibers are damaged uniformly, testing the whole length of a nerve with this
      method may be beneficial in detection of a mild conduction abnormality.

PMID- 11572189
TI  - Carpal tunnel syndrome: a system for categorizing and grading electrophysiologic
      abnormalities.
AB  - A system for classifying and grading electrophysiologic abnormalities in carpal
      tunnel syndrome is described. It is based on criteria for assessing severity of:
      1) focal nerve conduction slowing; 2) conduction block or dispersion in the
      responses; and 3) axonal loss. These criteria are applied separately to each
      component (sensory or motor) of the median nerve. The focal sensory conduction
      velocity (CV) slowing across the carpal tunnel is measured from ratios of the
      wrist-to-palm CVs to palm-to-finger sensory CVs; and motor conduction slowing,
      from ratios of the wrist-to-palm CVs to elbow-to-wrist motor CVs. The amount of
      amplitude loss due to dispersion or conduction block at the carpal tunnel is
      calculated from the amplitude ratios of the responses (sensory or motor) evoked
      at the wrist to those evoked at the palm. Axonal loss is estimated from reduction
      in the absolute amplitudes of sensory or motor responses evoked at the palm. This
      classification scheme is relatively simple, and it not only quantifies the
      abnormality, but it also suggests the pathophysiology.

PMID- 11572190
TI  - Electromyographic study of newborn stepping in neonates and young infants.
AB  - The purpose of this study was to examine the developmental changes in the
      functional mechanisms of leg muscles in newborn stepping over the first four
      months in ten normal neonates. Neonatal stepping in the first month showed
      excessive coactivation, that is, co-contraction patterns of mutual antagonists
      appeared especially during stance phase. The discharge patterns of co-contraction
      in neonatal stepping began to change to reciprocal patterns in young infant
      stepping (after the first month), but excessive muscular activities associated
      with a slightly squatted posture and forward lean still remained. Strong muscle
      activities of leg extensors due to a parachute reaction of the legs before floor
      contact, not seen in the neonatal period, began to appear in the young infant
      period from one month of age to three months. We suggest that these gradual
      changes of leg muscular activity in newborn stepping are evoked by development of
      balance, postural control, and strength, thereby modulating the neonatal stepping
      reflex.

PMID- 11572191
TI  - Paradoxical phenomenon of physiological tremor in prolonged tapping load.
AB  - Cumulative fatigue caused by a tapping load is investigated by power spectrum
      analysis of both physiological tremor of the finger and surface electromyogram
      (EMG) of the forearm muscle controlling the finger. A load for two hours at a
      rate of 200 taps/minute is performed on ten male subjects. The physiological
      tremor and the EMG are measured before and during the load. The measurement is
      performed under the isometric contraction at 10% maximum voluntary contraction in
      the m. flexor digitorum superficialis. The total power and the slow wave ratio of
      the power spectrum are evaluated. During the load, both spectra of the
      physiological tremor and the EMG show the maximum total power at 30 minutes after
      the load. The total powers of both spectra, however, decrease in the period after
      60 minutes. Namely, the results of the physiological tremor and the EMG for
      prolonged load show the "paradox of fatigue." In order to elucidate the cause of
      the paradox of fatigue, the slow wave ratio of the EMG spectrum is studied. The
      ratio increases during the load. The muscle loaded indicates the state close to
      exhaustion, and the change of the function of the muscle contraction affects the
      amplitude of the physiological tremor. Therefore, the criterion judging muscular
      fatigue is denoted due to the change of the amplitude of the physiological
      tremor.

PMID- 11572192
TI  - Neurophysiological investigation of cervical spondylosis.
AB  - The difficulties in diagnosing spinal cord lesions due to the cervical
      spondylosis is well-known in clinical neurology. In order to investigate the
      contribution of various neurophysiological examinations in the diagnosis in
      cervical spondylosis, we examined 70 patients suffering from cervical
      spondylosis, with peripheral nerve conduction studies, F-wave from the upper limb
      and electromyography from the corresponding muscles, as well as somatosensory
      evoked potentials (SEPs) from upper and lower limbs. Patients were separated into
      four groups: 20 patients had cervical spondylosis symptoms only; 15 patients had
      symptoms and signs of spinal root involvement; 15 patients had symptoms and signs
      of myelopathy; and 20 patients had symptoms and signs of both myelopathy and
      spinal root involvement. A group of 20 normal controls was also studied. In all
      groups of patients SEPs were the most sensitive electrophysiological study. Low
      amplitude N13 and increased conduction time of N9-N13 and central conduction N13
      N19 and LP-P27 were the most common finding in SSEP testing. SEPs were affected
      in many cases without CT-MRI findings of spinal cord pressure. From the above
      findings, SEPs proved to be the most sensitive diagnostic investigation in
      cervical spondylosis.

PMID- 11572193
TI  - Lumbosacral radiculopathic pain presenting as groin and scrotal pain: pain
      management with twitch-obtaining intramuscular stimulation. A case report and
      review of literature.
AB  - BACKGROUND: Chronic groin and scrotal pain is a common entity plaguing a
      significant population of young athletic individuals. Aside from urologic and
      visceral etiologies, there is a vast array of underlying musculoskeletal and
      spinal abnormalities that may be found in these individuals. FINDINGS: Presented
      is a patient found to have chronic, spine-related groin and scrotal pain
      diagnosed with lower lumbar discogenic disease by physical examination findings,
      imaging studies and multi-level chronic radiculopathy by electrodiagnostic
      studies who was treated with twitch-obtaining intramuscular stimulation (TOIMS).
      Symptoms of groin and scrotal pain abated with therapy. CONCLUSION: Twitch
      obtaining intramuscular stimulation has a promising role in the treatment of
      groin and scrotal pain of radiculopathic origin.

PMID- 11572194
TI  - 4th European Congress on Personality Disorders: New Trends in Personality
      Disorders. Paris, France, 21-24 June 2000. Proceedings and abstracts.

PMID- 11572196
TI  - Abstracts of the 1st United Kingdom Radiation Oncology Conference. York, 23-25
      April 2001.

PMID- 11572195
TI  - Slowly Aging Organisms. 22-23 September 2000, Los Angeles, California, USA.
      Proceedings.

PMID- 11572197
TI  - Proceedings of the 25th annual meeting of the Japanese Society of Sleep Research.
      8-9 June 2000, Yokohama, Japan.

PMID- 11572198
TI  - [Cancer research and treatment. Special issue in honor of Gerd A. Nagel].

PMID- 11572199
TI  - Proceedings of the 2nd International Symposium on Biological Chirality. Szeged,
      Hungary, August 27-31, 2000.

PMID- 11572200
TI  - Did the President go far enough?

PMID- 11572201
TI  - More on allopathic medical credentialing.

PMID- 11572203
TI  - Abstracts of the 1st scientific meeting of the Working Group on Cardiovascular
      Magnetic Resonance of the Society of Cardiology (EURO CMR 2000).

PMID- 11572204
TI  - Special issue: Anthropology and genetic markers. Papers presented at the HLA and
      Anthropology Workshop. 28 March 2001, Kansas City, Missouri, USA.

PMID- 11572202
TI  - The role of beta-blockade in modern cardiovascular therapy. Proceedings of the
      3rd International Symposium on Bisoprolol. Barcelona, Spain, September 29-October
      1, 1989.

PMID- 11572205
TI  - [The 74th congress of the Japanese Biochemical Society. Kyoto, Japan.  October 25
      28, 2001. Abstracts].

PMID- 11572206
TI  - An early Arabidopsis demonstration resolving a few issues concerning
      photorespiration.

PMID- 11572208
TI  - Yet another statistic to index baroreflex function.

PMID- 11572207
TI  - Immediate mobilization following fixation of mandible fractures: a prospective,
      randomized study.
AB  - OBJECTIVES: To compare outcomes of open reduction and internal fixation of
      displaced mandible fractures followed by either immediate mobilization or 2 weeks
      of mandibular-maxillary fixation. STUDY DESIGN: A prospective, randomized, single
      blinded study was performed. METHODS: The study was performed between January 1,
      1997, and March 30, 2000. Inclusion criteria were displaced fractures between the
      mandibular angles, age greater than 16 years, and no involvement of the alveolus,
      ramus, condyles, or maxilla. All fractures were repaired by means of open
      reduction and internal fixation using 2.0-mm titanium plates secured either in
      transoral fashion or percutaneously. Data were collected at 6-week and 3- and 6
      month postoperative examinations. Variables were assessed by a surgeon blinded to
      the history of immobilization and included pain, malunion or nonunion, occlusion,
      trismus, wound status, infection rates, dental hygiene, and weight loss. Twenty
      nine consecutive patients were enrolled, 16 patients to immediate function and 13
      patients to 2 weeks of mandibular-maxillary fixation. RESULTS: No statistically
      significant differences were found between groups for any of the variables.
      Immediate release and temporary immobilization showed mean weight loss of 10 and
      8 pounds and trismus of 4.2 and 4.6 cm, respectively. One wound separation and
      one infection were seen in the immobilization population, and no wound separation
      or infection was seen in the immediate-release group. Dental hygiene was similar
      between the groups. No malunion or nonunion was noted in either group.
      CONCLUSIONS: In this prospective and randomized study, no significant differences
      were noted between the groups receiving either immediate release or 2 weeks of
      mandibular-maxillary fixation. The findings support the treatment of selective
      mandible fractures with 2.0-mm miniplates and immediate mobilization.

PMID- 11572209
TI  - A note on the interval between infecting and secondary cases of yellow fever from
      the records of the yellow fever at Orwood and Taylor, Mississippi in 1898.

PMID- 11572210
TI  - Public Law No. 858 (70th Congress), February 28, 1929 .

PMID- 11572211
TI  - Treatment of hookworm disease in 1911.

PMID- 11572213
TI  - Getting a good night's sleep.

PMID- 11572212
TI  - American Association of Blood Banks 54th annual meeting. October 13-17, 2001. San
      Antonio, Texas, USA. Abstracts.

PMID- 11572215
TI  - XIII International Biophysics Congress. 19-24 September 1999. New Delhi, India.
      Abstracts.

PMID- 11572216
TI  - European Society of Head and Neck Radiology 14th annual meeting and European
      Society of Neuroradiology XXVII Congress. Ancona, Italy, 13-16 September 2001.
      Abstracts.

PMID- 11572214
TI  - An unusual etiology of persistent cough in an 8-year-old girl with cystic
      fibrosis.

PMID- 11572217
TI  - American Society for Reproductive Medicine 57th annual meeting. October 20-25,
      2001. Orlando, Florida, USA. Abstracts.

PMID- 11572218
TI  - Pacing and hypertrophic cardiomyopathy.

PMID- 11572219
TI  - Industry-sponsored research: science without a net?

PMID- 11572220
TI  - Hair removal using the long-pulsed ruby laser in children.
AB  - OBJECTIVE: The purpose of this study was to assess the efficacy of laser assisted
      hair removal in children aged 16 and under using the long pulsed ruby laser.
      BACKGROUND DATA: Unwanted hair in the pediatric population can be due to
      congenital hairy nevi and hypertrichosis. Methods of effecting hair removal
      include shaving, electrolysis, and laser depilation. The long-pulsed ruby laser
      is an established treatment modality in adults, but its use specifically in
      children has not been investigated. METHODS: Patients aged 16 or under undergoing
      treatment with the ruby laser for unwanted hair were assessed. Hair counts were
      determined before and after treatment and an assessment of overall satisfaction
      was made using a parental questionnaire. RESULTS: Treatment was regarded as
      successful in 25 out of 28 cases where there was a clear reduction in hair growth
      at the site treated with an average fall in hair count of 63% at 6 months follow
      up. There was no scarring or hyperpigmentation in this group and no serious
      complications. Total suppression of hair growth was not permanent but usually
      lasted between 3 and 6 months. Few problems were encountered from using the
      technique specifically in children, and pain was well controlled in most cases.
      CONCLUSIONS: We would recommend the long-pulsed ruby laser as a useful form of
      hair removal in children that is quick, simple and well tolerated. At present,
      the technique leads to hair loss that is temporary but most patients and their
      parents feel the treatment gives worthwhile benefits.

PMID- 11572221
TI  - Clinical application of laser-induced breakdown spectroscopy to the analysis of
      teeth and dental materials.
AB  - OBJECTIVES: The luminous plasma generated during laser ablation of dental tissue
      and dental materials has been analyzed to determine qualitative and quantitative
      elemental composition. BACKGROUND DATA: The use of pulsed lasers for controlled
      material ablation now is frequently suggested as an alternative to mechanical
      drilling for the removal of caries and in tooth modification. Spectral analysis
      of the ablated plasma can be exploited to monitor precisely the laser drilling
      process in vivo and in real time. METHODS: Teeth samples and dental materials
      were ablated using pulses from a Nd:YAG laser. The line positions and intensities
      in the spectra, recorded in real time, were used to identify elements and to
      determine their relative concentrations. RESULTS: From the spectra of
      horizontally and vertically cut tooth slices, profiles of elemental distribution
      were determined; these were used in a range of monitoring applications. We showed
      that the transition from caries to healthy tooth material could be identified
      through the decrease in calcium (Ca) and phosphorus (P) concentrations, whereas
      nonmineralizing elements and organic materials increased in concentration. We
      also could relate the spatial distribution of elements to their migration or
      accumulation over time, for example, the migration of aluminium (Al) from dental
      restorative materials to the tooth matrix. CONCLUSIONS: The plasma existing
      during laser ablation (in vitro/in vivo) can be analyzed spectrally in real time.
      From the spectra, one can pinpoint high/low levels of element concentrations
      within the tooth matrix. Thus, this analysis could be used to monitor the
      ablation of material during laser dental treatment.

PMID- 11572222
TI  - Low-power laser irradiation increases cyclic GMP synthesis in penile smooth
      muscle cells in vitro.
AB  - OBJECTIVE: The objective of the present study was to determine the effect of low
      power laser irradiation (LPLI) on cyclic guanosine monophosphate (cGMP) produced
      by human corpus cavernosum smooth muscle cells (HCC SMC) in vitro. BACKGROUND
      DATA: Numerous reports suggest that LPLI is capable of affecting cellular
      processes in the absence of significant thermal effect METHODS: HCC SMC cultures
      were irradiated with single-dose LPLI using a He-Ne continuous wave laser (632
      nm) with different energy densities (0.52-2.1 J/cm2). Assessment of effect on
      cell viability was performed utilizing Alamar Blue assay. Effect of LPLI on cGMP
      production was studied by radioimmunoassay. RESULTS: We observed that: (1) LPLI
      of HCC SMC results in a statistically significant increase of cGMP synthesis in
      culture and is dose dependent (maximal effect was observed with LPLI irradiance
      of 1.57 J/cm2. (2) There were no changes in Normalized Viability Index (NVI)
      immediately after and 24 h following laser irradiation. CONCLUSION: Our studies
      demonstrate that LPLI irradiation stimulates elevation of cGMP in vitro.

PMID- 11572223
TI  - Safety of the ArF193 excimer laser for the removal of dental plaque and calculi:
      an in vitro histological study.
AB  - OBJECTIVE: To assay the safety of the ArF excimer laser in the integrity of human
      pulp elements. BACKGROUND DATA: The use of lasers in dentistry remains
      controversial, in spite of their increasing application in medical practice. The
      main reason for this discrepancy is the frequent report of damage to surrounding
      tissues and the dental pulp, due to the energy transfer, from the site of laser
      impact. The progress made on laser technology during the last 10 years, could
      overcome this obstacle and allow the use of lasers in dentistry. METHODS AND
      RESULTS: The present study reports the use of the ArF 193 excimer laser, under
      conditions of strict control of frequency and fluency, for the ablation of dental
      carries, plaque, and calculi, by the use of a new, articulated arm. We have
      tested 10 teeth, extracted for prosthetic reasons, immediately after extraction.
      Our in vitro results show that the ArF193 excimer laser does not produce any harm
      to the dental pulp (at least at the photo- or electronic microscopy level),
      whereas in a matter of seconds, it can be effective in removing all dental
      deposits. In addition, the use of the flexible articulated arm, makes this
      treatment comfortable and easier for both the dentist and patient. CONCLUSION:
      Under a strict control of laser technology, and the use of the new articulated
      arm presented, the use of the ArF excimer laser in dentistry is safe and
      comfortable.

PMID- 11572224
TI  - A review of technical and clinical aspects of biliary laser lithotripsy.
AB  - OBJECTIVE: This paper reviews the current use of laser techniques for the
      treatment of biliary stones. BACKGROUND DATA: Biliary stones may pose a special
      problem when access to them is limited, when previous attempts of removal have
      failed, or when a less invasive option than surgery is needed. The availability
      of various laser sources and the adaptation of the technology for safe use in the
      biliary system make the use of laser energy for stone fragmentation possible.
      METHODS: Current literature is reviewed concerning the use of laser for biliary
      lithotripsy, including experimental data and experience with human series.
      Technology, indications, alternatives, and cumulative world experience are
      discussed. CONCLUSIONS: Recent technical advances have made the use of laser
      energy for fragmentation of biliary calculi possible. It is a valid option for
      treatment of "difficult" stones, when other methods have failed or as a primary
      treatment in certain situations. The technical complexity and the high cost limit
      its use for specialized centers.

PMID- 11572226
TI  - Laser literature watch.

PMID- 11572225
TI  - Low-level laser therapy after molar extraction.
AB  - OBJECTIVE: The aim of the study was to evaluate effect of the different
      frequencies of low-level laser radiation (diode 670 nm and Helium-Neon 632.8 nm)
      on the healing process after human molar extractions. Frequencies of 5 Hz, 292
      Hz, and 9,000 Hz were used in experiments. Monitoring of secretory IgA and
      albumin level in saliva and changes in bone density were used as objective
      markers of biostimulatory effect. SUMMARY BACKGROUND DATA: From the literature,
      it is known that if the alveolus is irradiated after extraction along with the
      lingual and buccal bony wall, faster coagulation, less postoperative discomfort,
      and quicker healing can be expected. METHODS: Subjective evaluation of therapy
      was observed using a scale (from -, negative therapeutic effect, to ++++,
      excellent treatment effect). Changes of secretory immunoglobulin A (sIgA),
      albumin levels, and bone density were compared in a group of 150 patients
      (nonlaser therapy, 30 patients). RESULTS: Differences in levels of the saliva
      markers (sIgA and albumin) were found to be significant when comparing irradiated
      and nonirradiated groups, and in comparison with those groups irradiated by
      various modulatory frequencies. Significant differences were observed between the
      increase of sIgA res. albumin and subjective feelings during treatment. Bone
      density after extraction and 6 months after surgical treatment was examined using
      dental digital radiovisiography. No significant differences were detected between
      bone density in irradiated and nonirradiated groups, perhaps due to our therapy
      protocol. CONCLUSIONS: The low-level laser has no influence on the process of
      osseointegration. This effect was observed on fracture healing in rats using He
      Ne laser radiation. We found no differences in the bone density when compared to
      the control group.

PMID- 11572227
TI  - No DNA sequence copy number changes in essential thrombocythemia.

PMID- 11572229
TI  - The American Society for Histocompatibility and Immunogenetics 27th annual
      meeting. October 13-17, 2001. San Francisco, California, USA. Abstracts.

PMID- 11572228
TI  - 26th Sir Peter Freyer Memorial Lecture 2001 in association with the Irish Society
      of Surgical Oncology. Galway, 7-8th September 2001. Abstracts.

PMID- 11572230
TI  - American Dietetic Association 2001 Food and Nutrition Conference. St Louis,
      Missouri, USA. October 20-23, 2001. Abstracts.

PMID- 11572231
TI  - [II National Congress of the Italian Society of Pathological Anatomy and
      Diagnostic Cytopathology. Torino, 23-27 September 2001. Abstracts].

PMID- 11572232
TI  - DMSAs after UTI--scan more children, not less.

PMID- 11572233
TI  - Age specific aetiology of anaphylaxis.

PMID- 11572234
TI  - Differential human immunodeficiency virus-suppressive activity of reverse
      transcription inhibitors in resting and activated peripheral blood lymphocytes:
      implications for therapy.
AB  - OBJECTIVES: Because recent evidence indicates that human immunodeficiency virus
      type 1 (HIV-1) propagates in resting T lymphocytes in vivo, we wanted to evaluate
      the antiviral effects exerted by currently used nucleoside (NRTI) and non
      nucleoside analog reverse transcription inhibitors in resting lymphocytes, and
      compare those effects to the ones obtained in activated lymphocytes. METHODS:
      Tissue culture antiviral assays in which target cells are lymphocytes present in
      a resting or activated state. Virus replication was measured by a reverse
      transcription (RT) assay. Cell viability was evaluated using a commercial 3-(4k5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS: In vitro
      results obtained with concentrations of zidovudine and stavudine equivalent to
      drug levels found in plasma, showed more than 99% HIV-1 inhibition in activated
      lymphocytes but less than 50% virus inhibition in resting lymphocytes.
      Conversely, plasma levels of didanosine-inhibited HIV-1 by approximately 50% and
      98% in activated and resting lymphocytes, respectively. Plasma level
      concentration of zalcitabine, lamivudine, and abacavir inhibited viral
      replication by more than 90% in both resting and activated cells. CONCLUSIONS:
      These data demonstrate that specific NRTI antiretroviral agents have different
      activity against HIV RT, depending on the state of cell cycle of the infected
      cell. We suggest that the replication of HIV-1 in resting lymphocytes should be
      taken into account in the design of future clinical trials, as well as treatment
      antiretroviral regimens. Selection of combination RTIs so that they provide
      antiretroviral activity in both resting and activated lymphocytes may be a way to
      minimize treatment failure and the emergence of drug-resistant variants.

PMID- 11572235
TI  - 2001 International Meeting of the Institute of Human Virology. September 9-13,
      2001. Baltimore, Maryland, USA. Abstracts.

PMID- 11572236
TI  - Of periscopes, telescopes and microscopes: medicine through the looking-glass.

PMID- 11572237
TI  - Low-level laser therapy for wound healing: feasibility of wound dressing
      transillumination.
AB  - OBJECTIVE: The purpose of this study was to assess the feasibility of exposing
      wounds during low-level laser therapy (LLLT) by transillumination of the wound
      dressings. BACKGROUND DATA: LLLT has been associated with accelerated wound
      healing in chronic ulcers. The usual approach is to remove wound dressings prior
      to exposure and to treat three to five times weekly. Frequent change of wound
      dressings is time consuming and costly; it disrupts the healing process,
      increases the risk of wound infection, and may be traumatic for the patient.
      METHODS: A double integrating sphere setup was employed to quantify the diffuse
      transmittance and reflectance of various wound dressings. Differences in
      transmittance for large area sources and point sources were demonstrated through
      the use of a diode laser and an incoherent light source. RESULTS: There were a
      number of gels and membrane style wound dressings with diffuse transmittance of
      more than 50%. Hence, for these dressings the prescribed radiant exposure to the
      wound surface could be achieved by increasing the exposure duration, while
      maintaining reasonable overall treatment times. CONCLUSIONS: Although LLLT by
      transillumination of wound dressings is feasible for a variety of wound dressings
      without significant commitments in additional treatment time, the specific
      transmission of products not included in this study needs to be determined at the
      intended treatment wavelength. A transillumination approach may facilitate a
      faster rate of wound healing than LLLT applied to exposed wounds by reducing
      trauma and the risk of infection.

PMID- 11572238
TI  - Removal effects of the Nd:YAG laser and Carisolv on carious dentin.
AB  - OBJECTIVE: The purpose of this study was to investigate the removal effect of the
      Nd:YAG laser irradiation and Carisolv on carious dentin. BACKGROUND DATA: Many
      previous studies have reported several simple and alternative techniques, such as
      lasers and chemicals, for caries removal. METHODS: Carisolv was applied on the
      surface of 20 extracted human anterior and molar teeth for 1 min and then the
      Nd:YAG laser was irradiated with a continuous water spray for another 1 min. The
      energy densities were varied from 2 to 6W with a repetition rate of 20 pps. As
      caries removal progressed, the cavity was carefully assessed by DIAGNOdent. Each
      lesion was photographed before and after treatment, and the treated cavity was
      observed microscopically using a stereoscope and with scanning electron
      microscope (SEM). Thermal change at the time of laser irradiation was measured by
      thermovision. RESULTS: Our results revealed that application of Carisolv followed
      by Nd:YAG laser irradiation at 4-6W pulse energy effectively removed dentin
      caries. The total procedure was usually repeated once or twice for complete
      caries removal. From the SEM study, it was found that the cavity surface treated
      with the laser revealed various patterns of microirregularity, often accompanied
      by microfissure propagation. There was also no smear layer. CONCLUSIONS: It was
      revealed that Nd:YAG laser and Carisolv could provide an alternative technique
      for caries removal instead of the conventional mechanical drilling and cutting.

PMID- 11572239
TI  - Results of clinical trials of transmyocardial laser revascularization versus
      medical management for end-stage coronary disease.
AB  - BACKGROUND DATA: Over 5,000 patients worldwide have undergone transmyocardial
      laser revascularization (TMR) since 1990 for the treatment of myocardial ischemia
      due to end-stage coronary artery disease. Recently, four prospective randomized
      controlled clinical trials have reported their results in comparing TMR to
      maximal medical therapy. The purpose of this review is to provide an update and
      comparison of the results of these trials. METHODS: Patients with severe angina
      were randomized to treatment by laser TMR (carbon dioxide or holmium YAG) or
      continuing on maximum medical therapy. All patients were followed for a year and
      had reassessment of angina class and quality of life at that time. RESULTS: All
      of the trials demonstrated that TMR provided significant relief of angina when
      compared to medical management. Additional objective data in the form of exercise
      tolerance and myocardial perfusion scanning was used to support the symptomatic
      improvement. CONCLUSION: Symptomatic improvement is seen for patients with severe
      diffuse coronary artery disease treated by TMR.

PMID- 11572240
TI  - Nd:YAG laser influence on tensile bond strength of self-etching adhesive systems.
AB  - OBJECTIVE: We evaluated the tensile bond strength of composite resin on enamel
      and dentine, treated with Nd:YAG laser before and after bonding procedures.
      BACKGROUND DATA: The use of laser radiation in dentistry is being developed day
      by day. One of the possible applications of dental lasers includes increasing the
      quality of self-etching bonding systems. METHODS: Forty-eight human teeth were
      used and separated into six groups: Group 1 (enamel control), Clearfil Liner Bond
      2V (CLB 2V); group 2 (enamel), Nd:YAG + CLB 2V; group 3 (enamel), CLB 2V +
      Nd:YAG; group 4 (dentine control), CLB 2V; group 5 (dentine), Nd:YAG + CLB 2V;
      group 6 (dentine), CLB 2V + Nd:YAG. Tensile bond strength was performed. RESULTS:
      Enamel means (15,54) were lower than dentine means (20,38). Bond strength of
      laser before (15,73) was lower than laser after (20,65). Interaction results G1 x
      G3; G2 x G3; G4 x G1; G2 x G5 were statistically significant. CONCLUSIONS:
      Tensile bond strength of composites reached with self-etching adhesive systems
      were greater in dentine than in enamel. The best moment for application of Nd:YAG
      laser is after the use of adhesive system. Self-etching adhesive systems tested
      in this study can be used together with Nd:YAG laser without compromising to
      adhesion to dentine.

PMID- 11572241
TI  - 350 ambulatory hemorrhoidectomies using a scanner coupled to a CO2 laser.
AB  - OBJECTIVE: The purpose of this study was to investigate how a scanner device
      would improve the outcome of laser hemorrhoidectomy regarding pain, healing,
      secretion, and hemostasis. BACKGROUND DATA: The technology of the laser has been
      applied since the 1960s in several clinical and surgical specialties. The
      inherent advantages, due to the biological characteristics of this instrument
      are: (1) it does not affect the neighborning tissues, (2) it is hemostatic, (3)
      it favors healing, (4) it is bactericidal, and (5) it presents less postoperative
      pain. Several authors have questioned these supposed advantages. After scanners
      were introduced, better results were accomplished, including in proctological
      surgery. METHODS: A total of 350 patients, consecutively, went through a laser
      hemorrhoidectomy using a CO2 laser coupled to a scanner device in a 3-year
      period. Patients were monitored for pain, healing, bleeding, and local secretion
      for up to 36 months. RESULTS: Almost 13% of the patients required bondage of
      arteries during the operation; 96% used analgesics for up to 3 days; and 5
      patients (1.42%) complained of strong pain for several days. Only 2 patients
      (0.6%) reported intense pain for more than 7 days. All patients presented
      complete healing between the 30th and the 40th POD. In the 90th POD tissue
      regeneration appeared healthy. The immediate complications included 2 cases of
      nipple hemorrhage that demanded a review. Stenosis occurred in 4 patients.
      Residual "plicoma" was often present with the laser technique (20%). Return to
      work, regardless of its nature, was an average, on the 3rd postoperative day.
      CONCLUSIONS: Our evaluation of the results led to the conclusion that the scanner
      coupled to the CO2 laser was fundamental for better postoperative outcome in our
      patients, at least compared to other laser techniques.

PMID- 11572243
TI  - Laser literature watch.

PMID- 11572242
TI  - Removal of gingival melanin pigmentation with the semiconductor diode laser: a
      case report.
AB  - OBJECTIVE: This investigation was performed to evaluate the possibility of the
      removal of canine gingival melanin pigmentation with the semiconductor diode
      (SCD) laser in vivo. SUMMARY BACKGROUND DATA: Recently, a semiconductor laser,
      which can ablate soft tissue, has been developed. It is already used in dentistry
      as well as in medicine. METHODS: The SCD laser was irradiated on the pigmented
      area of canine gingival surface with the irradiation output of 3W. The effect of
      the SCD laser irradiation was evaluated at the two intervals: immediately after
      irradiation and at 3 weeks following irradiation. In addition, histological
      examination was performed before irradiation and at the same intervals from the
      biopsies (4 microm) of unlased and lased areas. RESULTS: The SCD laser was
      effective in removing melanin pigmentation. In histological examination, neither
      inflammatory cell nor any tissue damage was observed with hematoxylin-eosin
      staining. At 3 weeks, there was a continuous healing process with the
      proliferation of squamous epithelial cells. CONCLUSIONS: SCD laser irradiation
      can be considered an alternative procedure for removal of melanin pigmentation.

PMID- 11572244
TI  - Polymers and copolymers science in the operating room.

PMID- 11572245
TI  - Surgical buccinator muscle myotomy in dentoskeletal Class II alterations.
AB  - Recent studies on autoptic findings have underlined the complexity of perioral
      muscles; the discovery of a fourth band of buccinator muscle and the effects it
      can have on teeth, alveolar bone, and oral mucosa during growth has stressed the
      importance of muscular influence on the genesis of and therapy for basal class II
      dentofacial alterations. Frederick proposed a surgical marginal myotomy to
      elongate the buccinator bundle together with inferior vestibuloplasty to unload
      the jaw from the overcontraction of the muscle and to reduce the inferior lip
      hypotone. In our investigation, we have applied this technique on a group of 50
      patients with basal class II defect selected according to our protocol before
      functional or fixed orthodontics, and we have recorded and compared cephalometric
      measurements and clinical facial profile changes 12 (T1) and 24 (T2) months after
      the end of therapy to a control group with the same defect treated only with
      orthodontic functional devices. We obtained improvement of cephalometric
      parameters in 80% of patients who underwent surgery and orthodontics, and in only
      50% of patients who underwent only orthodontics. Results suggest that
      neutralizing buccinator and mental muscles pressure on the jaw during growth can
      help the clinician dealing with II basal malocclusion therapy and relapse.

PMID- 11572246
TI  - Establishment of normative data for orbital and nasal soft-tissue measurements
      among Filipino children.
AB  - This article establishes the soft-tissue norms among Filipino children from ages
      birth to 17 years of age. Specific measurements were made at the inner canthal
      region, the outer canthal region, and the nasal length. This was to help
      establish normative graphs among this population of children.

PMID- 11572247
TI  - Parotid gland carcinoma: surgical strategy based on local risk factors.
AB  - To evaluate the best surgical strategy in cases of parotid gland carcinoma, local
      risk factors (T, N, histology, and treatment) were analyzed in a series of 134
      patients. The efficacy of the facial nerve sacrifice in case of macroscopic tumor
      infiltration was tested by means of survival analyses (Kaplan-Meier and Cox
      algorithms). This study demonstrated that nerve preservation resulted in a better
      prognostic value when compared with resection only in the group of patients
      having a T1 or T2. In patients affected by T3 and T4, the different treatment did
      not show any difference in survival rate. In conclusion, the sacrifice of the
      facial nerve is not always able to improve the survival rate.

PMID- 11572248
TI  - Unresectable primary tumor of head and neck: does neck dissection combined with
      chemoradiotherapy improve survival?
AB  - A study regarding patients with primary and previously untreated advanced
      histologically proven squamous cell carcinoma of the head and neck was performed
      to compare two treatment modalities: neck dissection followed by
      chemoradiotherapy (Group I) versus chemoradiotherapy alone (Group II). Fifty-four
      patients were randomly chosen to receive Group I or II treatment. Our results
      demonstrate that Group I treatment has a higher and statistically significant
      disease-specific survival rate. We suggest that an association of neck dissection
      plus chemoradiotherapy can be useful in the event of unresectable advanced
      carcinomas.

PMID- 11572249
TI  - A mouse model of mandibular osteotomy healing.
AB  - The purpose of this study was to establish a novel mouse model of membranous
      osteotomy healing. By applying this model to transgenic mice or using in situ
      hybridization techniques, we can subsequently investigate candidate genes that
      are believed to be important in membranous osteotomy healing. In the current
      study, 20 adult male CD-1 mice underwent a full-thickness osteotomy between the
      second and third molars of the right hemimandible using a 3-mm diamond disc and
      copious irrigation. Compo-Post pins were secured into the mandible, 2 mm anterior
      and posterior to the osteotomy. After the soft tissues were reapproximated and
      the skin was closed, an acrylic external fixator was attached to the exposed
      posts for stabilization. The animals were killed on postoperative day number 7,
      10, 14, and 28 (n=5 animals per time point). The right hemimandibles were
      decalcified and embedded in paraffin for histologic evaluation or
      immunohistochemistry localizing osteocalcin. At 7 days after the osteotomy, early
      intramembranous bone formation could be seen extending from either edge of the
      osteotomized bone. By 10 days, an increasing number of small blood vessels could
      be seen within and around the osteotomy. At 14 days, the bone edges were in close
      approximation, and by 28 days the callus had been replaced by actively remodeling
      woven bone in all specimens examined. Immunohistochemistry demonstrated that
      osteocalcin expression correlated temporally with the transition from a soft to a
      hard callus. Furthermore, osteocalcin was spatially confined to osteoblasts
      actively laying down new osteoid or remodeling bone. This study describes a novel
      mouse model of membranous osteotomy healing that can be used as a paradigm for
      future osteotomy healing studies investigating candidate genes critical for
      osteogenesis and successful bone repair.

PMID- 11572250
TI  - Outcome analysis for correction of single suture craniosynostosis using
      resorbable fixation.
AB  - A retrospective review was performed on 63 patients at Childrens Healthcare of
      Atlanta at Scottish Rite who underwent correction of single-suture
      craniosynostosis using a resorbable fixation system. Included in the series were
      24 patients with metopic synostosis, 15 with sagittal synostosis, and 24 with
      unicoronal synostosis. The average age at operation was 22.7 months (range: 2.8
      months-18 years), and mean follow-up time was 30.7 months (range: 7.1-10 years).
      Reoperation equal to or exceeding the magnitude of the original procedure
      occurred in 4.76% of the patients. This was comparable to the reoperation rate
      observed at our institution using traditional fixation systems. Minor
      complications related to the use of resorbable plates were also identified, and
      the final outcome for single-suture synostosis was favorable. Results suggest
      that resorbable plates and screws are as effective as titanium-based systems in
      the treatment of single-suture synostosis.

PMID- 11572251
TI  - External distraction of the maxilla in patients with craniofacial dysplasia.
AB  - Patients with severe maxillary hypoplasia secondary to craniofacial dysplasia
      present a challenge to the craniofacial surgeon. Maxillary distraction presents a
      promising tool to treat these patients more successfully. Fifteen patients aged
      12 to 20 years with craniofacial dysplasia and maxillary retrusion were treated
      with two different techniques after complete Le Fort I osteotomy: one group
      underwent face mask protraction (2 patients), and the other group underwent rigid
      external distraction (13 patients). Cephalometric evaluation was performed before
      and after distraction. Rigid external distraction appeared to be superior to face
      mask protraction. Maxillary retrusion was fully corrected in this group. The path
      of maxillary positioning was well controlled by changing the traction force
      vector. Distraction osteogenesis has certainly improved treatment of these
      patients.

PMID- 11572252
TI  - Rare incidence of three consecutive primary tumors in the maxillofacial region:
      retinoblastoma, leiomyosarcoma, and choriocarcinoma: case report.
AB  - Multiple primary tumors occur more commonly in the region of the head and neck
      than elsewhere in the body. The chance of this is particularly high in patients
      treated for retinoblastoma, in part because of a genetic predisposition, and in
      part because of the possibility of irradiation treatment. However, triple tumors
      occur in only 0.5% of multiple tumors. A rare case of a triple (metachronous)
      tumor is reported: 12 years after the treatment of bilateral retinoblastoma
      (enucleation and irradiation), secondary leiomyosarcoma developed in the
      maxillofacial region, followed 5 years later by choriocarcinoma. Surgery was
      performed on all three types of tumor. As a result, the female patient (currently
      21 years old) is now free of complaints and has married. It is extremely rare for
      either leiomyosarcoma or choriocarcinoma (CHC) to appear in the maxillofacial
      region. The long-term, systematic control of such patients is absolutely
      necessary, for the multiple tumors tend to develop only after a long latency
      period of 10 to 20 years.

PMID- 11572253
TI  - Fibrous ankylosis after distraction osteogenesis of a costochondral neomandible
      in a patient with grade III hemifacial microsomia.
AB  - Distraction osteogenesis has recently become a mainstay for treatment of
      craniofacial syndromes with mandibular hypoplasia. This article presents the
      difficult case of a patient with a previous costochondral rib graft who underwent
      mandibular distraction and developed a fibrous pseudoarthrosis at the distraction
      site. This was attributed in part to an associated temporomandibular joint
      ankylosis. Resorption of the pseudoarthrosis occurred once the distractor was
      removed. It appears that distraction osteogenesis of a mandible with an ankylosed
      temporomandibular joint can result in healing with a fibrous union, presumably
      because of movement at the distraction site when masticating. This can result in
      a pseudo "temporomandibular joint" at the distraction site. A temporomandibular
      joint arthroplasty was performed, followed by repeat distraction. We conclude
      that if there is an ankylosed temporomandibular joint or a stiff
      temporomandibular joint that may ankylose during the course of the distraction
      process, then a temporomandibular joint arthroplasty should be performed before
      or at the time the distractor is placed.

PMID- 11572254
TI  - Miniplate osteosynthesis and cellular phone create disturbance of infraorbital
      nerve.
AB  - A 37-year-old man with a zygomatic fracture underwent surgical treatment with
      reduction of the fracture and osteosynthesis with a miniplate on the infraorbital
      rim. Postoperatively, he had numbness in the distribution area of the
      infraorbital nerve, but he also suffered from dysesthesia in the same area during
      periods when he was using his hand-held mobile phone. After surgical removal of
      the osteosynthesis plate, the dysesthesia associated with his mobile phone was no
      longer present. The plate was examined in a setup where we measured the electric
      current that developed on the surface of the plate under the influence of the
      magnetic field between the phone antenna and the metal plate. The highest
      currents measured on the actual plate were 141 mV in air, and 21 mV in saline.
      These findings indicate that there might have been a correlation between the
      presence of the miniplate close to the infraorbital nerve, and the dysesthesia
      experienced by the patient, under the influence of the energy emitted from the
      cellular phone.

PMID- 11572255
TI  - Surgical program for craniosynostosis using three-dimensional solid model,
      combined with autologous blood transfusion in a Japanese craniofacial unit.
AB  - Since April 1997 at St. Mary's Craniofacial Unit, simulated surgery using a three
      dimensional solid model made preoperatively was carried out, which enable
      sufficient autologous blood banking before the surgery. This study was conducted
      in eight patients presenting with plagiocephaly, brachycephaly, and oxycephaly
      consisting of simple craniosynostosis and syndromic craniosynostosis. Four cases
      (numbers 1-4) conducted with simulated surgery using three-dimensional solid
      models and fronto-orbital advancement with reshaping, as well as autologous blood
      transfusion were selected for the later-term group. For the first-term group,
      four cases (numbers 5-8) that were performed before the introduction of the
      abovementioned treatment were selected. The later-term group compared with the
      first-term group showed a decrease in operating time by an average of 1 hour,
      blood loss during surgery by 90 ml, and one fifth the amount of homologous blood
      transfusion. Also, 2 cases in the later-term group (cases 3 and 4) were able to
      avoid homologous blood transfusion, and they had autologous blood transfusion of
      30 to 33 ml/kg. The surgical techniques will be improved with repeated cases of
      simulated surgery, aiming for the minimum invasive surgery. Also, the use of
      autologous blood transfusion is expected to increase as a less invasive surgery.

PMID- 11572256
TI  - Angiodysplasia with osteohypertrophy affecting the oromaxillofacial area:
      clinical findings.
AB  - The authors report a case of oro-facial port-wine stain angiomatosis with
      cutaneous and mucosal lesions localized in the first and the second branch
      surface distribution areas of the right trigeminal nerve in association with
      right upper and lower lip, cheek, and hemimaxillary true hypertrophy leading to a
      severe dento-skeletal malocclusion with openbite and facial asymmetry. The
      authors through a revision of the Bibliography locate nosologically this case
      among the rare congenital angiodysplastic syndromes affecting the maxillo-facial
      district as the Sturge-Weber and the Klippel-Trenaunay syndromes. They debate
      also about etiopathogenetic, clinical, differential diagnosis, and therapeutic
      aspects concerning the treatment of patients affected by this kind of
      malformation.

PMID- 11572257
TI  - Reconstruction of shallow upper buccal sulcus deformity secondary to cleft lip
      and palate repair.
AB  - Shallow upper buccal sulcus deformity, one of the secondary deformities after
      cleft lip-palate repair, causes both aesthetic and functional problems. This
      deformity also prevents or makes difficult orthodontic and prosthodontic
      procedures. An upper buccal sulcus deepening procedure was performed in 14
      patients during the last 5 years. In 12 cases, premaxillary-based mucosal flaps
      were combined with one of the following: lip re-repair, Abbe flap, or bilateral
      buccal mucosal advancement flaps; in two cases, premaxilla was grafted with
      buccal mucosal graft together with bilateral buccal mucosal advancement flaps.
      The follow-up period was 2 to 5 years. Results were satisfactory for the surgeon,
      orthodontist, prosthodontist, and the patient. Upper buccal sulcus reconstruction
      with premaxillary thin mucosal flap or full-thickness mucosal graft combined with
      tissue-sparing techniques provides successful and durable results.

PMID- 11572258
TI  - Closure of an oronasal fistula in an irradiated palate by tissue and bone
      distraction osteogenesis.
AB  - Uses for distraction osteogenesis in the craniofacial skeleton have expanded
      during the last decade. It has become an important rung in the reconstructive
      ladder for correction of difficult defects. Distraction of irradiated bone has
      been successfully performed in an animal model but has not been reported in human
      subjects. We present a case of distraction osteogenesis in a patient with
      multiple failed reconstructive attempts to close an irradiated palatal defect. An
      additional benefit included improvement in support of the upper lip from bone
      transported and the potential for placing dental implants.

PMID- 11572259
TI  - Axial aponeurofasciocutaneous groin flap: an extended concept.
AB  - The concept of including external oblique aponeurosis along with the time-tested
      groin flap as a single vascularized unit heralds a versatile and unique
      application in the armamentarium presently available. This concept, though
      simple, has not been previously reported in the world literature. In view of its
      potential benefits and simplicity, we felt the need to bring this concept to the
      attention of our colleagues.

PMID- 11572260
TI  - Shortening of mandibular linear distance with multivector distraction.
AB  - It was noted that when a multivector distractor is used, there is shortening of
      the linear distraction distance when the gonial angle is reduced and the
      transverse distance is increased. The purpose of this study was to measure the
      distance change at the mandibular corticotomy site when the gonial angle is
      reduced or the transverse distance is increased. The Synthes multivector
      distractor was used in this experiment. After initial linear distraction, the
      distractor was activated by angular and transverse adjustments to achieve an
      angular, a transverse, and a combined angular and transverse reorientation. The
      length of the pin from the distractor to the tip of pin was evaluated at 15, 20,
      and 25 mm. With the pins place at 180 degrees , the distractor arm length was
      evaluated at 30, 35, 40, 45 and 50 mm apart, respectively. The distance change
      between the ends of the pins was measured by means of a caliper. For angular
      activation, one turn shortened the linear distraction distance at the pin end by
      1.5 to 2.2 mm. For transverse activation, one turn shortened the linear
      distraction distance by 1.1 to 2 mm. For combined angular and transverse
      activation, one turn of angular activation plus one turn of transverse activation
      shortened the linear distraction distance by 2.2 to 3.2 mm. For angular
      activation, increasing the pin length did not alter the distance between the pin
      ends for any of the specific activations. Increase in the distractor arm length
      in angular reduction resulted in significant increase in the shortening. For
      transverse increase, alteration in the distractor arm length resulted in the same
      shortening. Increase in the pin length resulted in increased shortening at the
      pin ends. When the transverse and angular activation were combined, the
      shortening was 80% of the combined measurements. The distance between the pin
      ends will reflect the distance between the bone segment at that site. It will be
      different at the outer cortex of the bone. These measurements will be valuable in
      planning the extent of additional linear distraction needed, when the angle is
      reduced or transverse distance is increased with the use of a multivector
      distractor. Alteration in the distractor arm length and pin length has a
      significant effect on the extent of shortening.

PMID- 11572261
TI  - Dental management of children with latex allergy.
AB  - This paper reviews the aetiology, epidemiology and dental management of children
      with latex allergy. The issue of latex allergy has serious consequences for the
      dental management of children with one or more of the following risk factors:
      spina bifida, atopy, first surgery before one year of age, history of multiple
      surgical procedures, congenital urologic abnormalities, gastrointestinal
      malformations, hydrocephalus internus, ventriculo-peritoneal shunts, spinal cord
      injuries, and family history of atopy. Management of latex allergy is based upon
      the diligent avoidance of latex exposure. Universal use of powder-free low
      allergen latex gloves is recommended.

PMID- 11572262
TI  - Avulsed permanent incisors: knowledge and attitudes of primary school teachers
      with regard to emergency management.
AB  - OBJECTIVES: This study was designed to examine the knowledge and attitudes of
      primary school teachers with regard to the emergency management of avulsed
      permanent incisors. DESIGN: Data were collected by self-administered
      questionnaire. SETTING: The study was conducted in primary schools lying within a
      2-mile radius of the University Dental Hospital, Cardiff. Sample and methods. A
      total of 388 teachers in 31 participating schools were asked to complete a
      questionnaire, which was subsequently collected by two of the authors (CS and
      AT). RESULTS: Two hundred and seventy-four teachers returned completed
      questionnaires, a response rate of 70.6%. One hundred and eighty-one respondents
      (60.1%) had received no advice about the emergency management of dental avulsion.
      Of the 133 teachers (48.5%) who possessed a first aid certificate, 39 (29.3%) had
      been given relevant advice as part of this training. Less than one-third of
      respondents (85 (31%)) cited an optimum extra-oral time of 30 min or less, with
      only 43 (15.7%) considering that this should be 10 min or less. However, 125
      (45.6%) knew milk to be the best transport medium. Two hundred and four teachers
      (74.5%) stated that they would not be prepared to replant an avulsed tooth
      themselves, 133 (80%) basing this decision on lack of expertise and training. Two
      hundred and sixty-two teachers (95.6%) expressed a desire for further
      information. CONCLUSIONS: The majority of respondents possessed, at best,
      rudimentary knowledge of the emergency management of dental avulsion. Teachers,
      and other individuals who supervise children in schools, should receive simple
      instruction in dental first aid.

PMID- 11572263
TI  - Tooth size and morphology in twins.
AB  - OBJECTIVE: To assess concordance of tooth size and occlusal morphology in
      monozygotic (identical) and dizygotic (non-identical) twins compared to unrelated
      controls in order to determine how much these dental traits are related to
      inheritance. METHODS: Mesiodistal and bucco-lingual dimensions of tooth size in
      34 pairs of twins were measured with dial calipers. In addition, the occlusal
      morphology of nine pairs of teeth was assessed using a co-ordinate measuring
      machine with a non-contact laser probe. RESULTS: The results showed greater
      concordance in tooth size for both mesiodistal and bucco-lingual dimensions
      within twin pairs compared to twin and unrelated controls. Furthermore,
      monozygotic (MZ) twins showed greater concordance than dizygotic (DZ) twins for
      all permanent teeth with statistically significant variance for the mesiodistal
      dimension (P = 0.01) but not bucco-lingual dimension. Superimposed computer
      models of the digitized occlusal surfaces showed a high degree of similarity for
      MZ twins compared to DZ twins. The mean intrapair deviation was 147 microm for
      MZ, 209 microm for DZ and 258 microm for unrelated controls. CONCLUSIONS: The
      remarkable similarity in the tooth size and morphology of monozygotic twins
      suggests a strong inheritability factor to tooth size and shape and that these
      may be useful as additional tools for zygosity determination along with other
      dental traits.

PMID- 11572264
TI  - A treatment decision-making model for infraoccluded primary molars.
AB  - The objective of this paper is to clarify the literature's findings and provide
      guidelines for decision-making during the long-term treatment planning of
      infraoccluded primary molars. This paper presents a synopsis of findings
      concerning prevalence, aetiology, diagnostic methods, diagnostic criteria and
      treatment options. Treatment decisions are mainly guided by the clinical
      assessment of the presence or absence of succedaneous tooth, evaluation of onset,
      time of diagnosis, resorption rate, rate of progression of infraocclusion, risk
      of adverse effects over time, and predictive clinical patterns of infraoccluded
      primary molars. These models are a result of a comprehensive review of the
      literature and presents a compilation of findings in a format that is of
      practical use to the clinician.

PMID- 11572265
TI  - Oral and dental care in acute lymphoblastic leukaemia: a survey of united kingdom
      children's cancer study group centres.
AB  - OBJECTIVES: To examine the provision of oral and dental care for children
      receiving treatment for acute lymphoblastic leukaemia (ALL) in United Kingdom
      Children's Cancer Study Group (UKCCSG) centres. SAMPLE AND METHODS: A postal
      questionnaire was sent to a named consultant at each centre. All 22 centres
      responded. RESULTS: The majority of centres carry out an oral assessment at the
      time of diagnosis, although various health care professionals are responsible for
      this. A dentist routinely attends out-patient clinics in only a minority of
      centres, although the majority have facilities for the provision of dental
      treatment 'on site'. In the main, children requiring dental treatment are
      referred to the Hospital Dental Service. Almost a quarter of centres do not have
      an oral care protocol. CONCLUSIONS: The development of appropriate dental
      services at tertiary referral centres should be vigorously pursued.

PMID- 11572266
TI  - Oral findings in Carpenter syndrome.
AB  - Acrocephalopolysyndactyly Type II (Carpenter Syndrome) is determined by autosomal
      recessive inheritance. Only some 40 cases have been described. Variable clinical
      signs have been described including prolonged retention of primary teeth and
      hypodontia. This paper describes the oral and dental findings in a family
      containing two affected brothers. The family pedigree is informative, as the
      mother has had children by three partners. The two affected individuals are full
      brothers. The first affected brother has delayed dental development, severe
      hypodontia and small tooth crown size. Mesio-distal and bucco-lingual dimensions
      were measured on the study models and compared with population data. The younger
      brother also has delayed dental development but only mild hypodontia. Their half
      sister has severe hypodontia but no signs of Carpenter Syndrome. This family
      study demonstrates two affected individuals with typical clinical features and a
      pedigree compatible with autosomal recessive inheritance. Small tooth crown size
      has been shown by standardized measurement and evidence advanced that hypodontia
      is not part of the syndrome but a coincidental finding which segregates
      independently. We have also shown that the marked delay in emergence of teeth is
      associated more with problems of tooth eruption, possibly related to the bony
      abnormalities, than to a generalized delay in dental development.

PMID- 11572267
TI  - The prevalence and pattern of nursing caries in Saudi preschool children.
AB  - OBJECTIVES: To determine the prevalence and pattern of nursing caries in Saudi
      preschool children of Riyadh area. DESIGN: Cross-sectional. SUBJECTS AND METHODS:
      A list of kindergartens was derived through random selection of one kindergarten
      from every area of Riyadh. A sample of 1,016 children with primary dentition only
      was examined for dental caries. The criterion used for nursing caries was
      presence of caries on the labial or lingual surfaces of at least two maxillary
      incisors with absence of caries in mandibular incisors. RESULTS: Two hundred and
      seventy-seven (27.3%) children were diagnosed as having nursing caries. The mean
      dmft of nursing caries children was 8.6 (+/- 3.4), with dt component of 7.6 (+/-
      3.5), mt of 0 4 (+/- 0.9) and ft of 0.6 (+/- 1.7). The older children had
      significantly higher mean dmft as compared with younger children. The teeth most
      affected by caries were maxillary central incisors (93.9%), whereas the least
      affected were mandibular canines (9.6%). A great majority of children (95.7%) had
      caries in both anterior and posterior teeth. The probability of bilateral molar
      caries was very high in nursing caries children; highest (94.7%) in mandibular
      first molars. CONCLUSIONS: The caries prevalence was high in the study
      population. The maxillary central incisors were most affected by caries. The
      probability of bilateral molar caries was very high.

PMID- 11572268
TI  - Evaluation of the palate dimensions of patients with perennial allergic rhinitis.
AB  - OBJECTIVE: The purpose of this study was to compare the transverse and vertical
      palate dimensions of two groups of children, one diagnosed as having perennial
      allergic rhinitis (PAR) and the other without any respiratory pathology. DESIGN:
      Case-control study. SETTING: Institute of Paediatrics and Child Care of the
      Federal University of Rio de Janeiro. SAMPLE AND METHODS: The sample consisted of
      101 children with the diagnoses of PAR (mean age 6.5) and 91 without any
      respiratory pathology (mean age 7.3). From 192 patients, 65% was in mixed
      dentition phase and 35% in primary dentition. Each subject underwent an intra
      oral clinical examination using three-dimensional Korkhaus compass to measure the
      intermolar distance, intercanine distance and palate depth. RESULTS: The allergic
      group showed greater averages of palate depth (P = 0.00), both in the primary
      dentition phase (11.53 mm x 10 mm) and in the mixed dentition (11.96 mm x 10.21
      mm). There was no statistically significant difference for intermolar and
      intercanine distances, either in primary or mixed dentition (P > 0.05).
      CONCLUSION: The transverse dimension of the palate did not vary significantly
      between the groups, which seems to confirm that the main influence of alteration
      of the breathing pattern from nasal to mouth occurs on the vertical plane.

PMID- 11572269
TI  - Dental fluorosis and caries experience in relation to three different drinking
      water fluoride levels in South Africa.
AB  - OBJECTIVES: The purpose of this study was to determine the relationship between
      caries experience, degree of fluorosis and different concentrations of fluoride
      in the drinking water of children. SAMPLE AND METHODS: The study included 282
      children aged 10-15 years, who lived continuously since birth in three different
      naturally fluoridated areas (Leeu Gamka, 3.0; Kuboe 0.48 and Sanddrif 0.19 p.p.m.
      F), with virtually no dental care or any fluoride therapy The teeth of the
      children were examined for caries using the DMFT index according to th WHO
      criteria and for fluorosis, using Dean's criteria according to the WHO
      guidelines. RESULTS: The prevalence of fluorosis (scores 2, 3, 4 and 5) among the
      school children was 47% in Sanddrif, 50% in Kuboes and 95% in Leeu Gamka. Almost
      half the children in the two low fluoride areas had no fluorosis (scores 0 and
      1), whereas only 5% in Leeu Gamka had no fluorosis. Of the children in Sanddrif,
      42.5% had very mild/mild (scores 2 and 3) fluorosis, 44.3% in Kuboes and 34.1% in
      Leeu Gamka. Except for one individual in Kuboes, severe fluorosis (score 5) was
      only observed in the high fluoride area in 30% of the children. According to the
      Bonferroni adaptation for multiple comparisons, the degree of fluorosis in Leeu
      Gamka differed significantly from both those of Sanddrif and Kuboes. The mean
      DMFT for the children in Sanddrif and Kuboe was similar (164 +/- 0.30 and 1.54 +/
      0.24, respectively) but the caries experience of Leeu Gamka (198 +/- 0.22) was
      significantly higher (P < 0.05) than that of both the other two areas. A strong
      positive correlation (P < 0.05) was found between the caries experience and the
      fluorosis scores of children in the high fluoride area (Leeu Gamka) but no
      correlation could be found in the other two areas. Significantly (P < 0.01) more
      children had decayed teeth in the high F area (Leeu Gamka) than in the other two
      areas. CONCLUSION: The results suggest a positive association between high F
      levels in the drinking water and dental caries. Furthermore, a low caries
      experience and no difference in DMFT and fluorosis between the two low fluoride
      areas were found.

PMID- 11572270
TI  - Bifurcation, birooted primary canines: a case report.
AB  - A rare case of birooted primary canines is reported. A male patient aged 6 years
      4 months of age presented with pain and swelling related to the upper right first
      primary molar. Radiographic examination revealed an incidental finding of
      bifurcation of the roots of all four primary canines. This represents a rare
      finding. The prevalence of birooted permanent canines in the Japanese population
      has been reported, but the prevalence of this abnormality of primary canines in
      other populations is unknown. This report discusses the findings in the context
      of the available literature. The possible aetiology, possible inferences for the
      developing dentition, and the need for careful assessment prior to root canal
      therapy or extraction are highlighted.

PMID- 11572271
TI  - Speed, air pollution, and health: a neglected issue.

PMID- 11572273
TI  - Lead levels in blood bank blood.
AB  - Although blood bank blood is usually screened for dangerous pathogens, the
      presence of toxic metals in blood has received little attention. Population blood
      lead levels have been declining in the United States, but occasional high
      outliers in blood lead concentration can be found--even when mean levels of blood
      lead are low. We sampled 999 consecutive blood bank bags from the King/Drew
      Medical Center, used between December 1999 and February 2000. The geometric mean
      blood lead level was 1.0 microg/dl (0.048 micromol/l), but 0.5% of the samples
      had lead levels that exceeded 10 microg/dl, and 2 samples had lead levels that
      exceeded 30 microg/dl. The 2 samples with the highest lead levels could have
      presented an additional risk to infants if they were used for blood replacement.
      Therefore, even in countries with generally low population blood lead levels,
      blood bank blood should be screened for lead concentration prior to use with
      infants.

PMID- 11572272
TI  - Embryo toxicity and teratogenicity of formaldehyde.
AB  - C-14 formaldehyde crosses the placenta and enters fetal tissues. The incorporated
      radioactivity is higher in fetal organs (i.e., brain and liver) than in maternal
      tissues. The incorporation mechanism has not been studied fully, but formaldehyde
      enters the single-carbon cycle and is incorporated as a methyl group into nucleic
      acids and proteins. Also, formaldehyde reacts chemically with organic compounds
      (e.g., deoxyribonucleic acid, nucleosides, nucleotides, proteins, amino acids) by
      addition and condensation reactions, thus forming adducts and deoxyribonucleic
      acid-protein crosslinks. The following questions must be addressed: What adducts
      (e.g., N-methyl amino acids) are formed in the blood following formaldehyde
      inhalation? What role do N-methyl-amino adducts play in alkylation of nuclear and
      mitochondrial deoxyribonucleic acid, as well as mitochondrial peroxidation? The
      fact that the free formaldehyde pool in blood is not affected following exposure
      to the chemical does not mean that formaldehyde is not involved in altering cell
      and deoxyribonucleic acid characteristics beyond the nasal cavity. The
      teratogenic effect of formaldehyde in the English literature has been sought,
      beginning on the 6th day of pregnancy (i.e., rodents) (Saillenfait AM, et al.
      Food Chem Toxicol 1989, pp 545-48; Martin WJ. Reprod Toxicol 1990, pp 237-39;
      Ulsamer AG, et al. Hazard Assessment of Chemicals; Academic Press, 1984, pp 337
      400; and U.S. Department of Health and Human Services. Toxicological Profile of
      Formaldehyde; ATSDR, 1999 [references 1-4, respectively, herein]). The exposure
      regimen is critical and may account for the differences in outcomes. Pregnant
      rats were exposed (a) prior to mating, (b) during mating, (c) or during the
      entire gestation period. These regimens (a) increased embryo mortality; (b)
      increased fetal anomalies (i.e., cryptochordism and aberrant ossification
      centers); (c) decreased concentrations of ascorbic acid; and (d) caused
      abnormalities in enzymes of mitochondria, lysosomes, and the endoplasmic
      reticulum. The alterations in enzymatic activity persisted 4 mo following birth.
      In addition, formaldehyde caused metabolic acidosis, which was augmented by iron
      deficiency. Furthermore, newborns exposed to formaldehyde in utero had abnormal
      performances in open-field tests. Disparities in teratogenic effects of toxic
      chemicals are not unusual. For example, chlorpyrifos has not produced teratogenic
      effects in rats when mothers are exposed on days 6-15 (Katakura Y, et al. Br J
      Ind Med 1993, pp 176-82 [reference 5 herein]) of gestation (Breslin WJ, et al.
      Fund Appl Toxicol 1996, pp 119-30; and Hanley TR, et al. Toxicol Sci 2000, pp 100
      08 [references 6 and 7, respectively, herein]). However, either changing the
      endpoints for measurement or exposing neonates during periods of neurogenesis
      (days 1-14 following birth) and during subsequent developmental periods produced
      adverse effects. These effects included neuroapoptosis, decreased
      deoxyribonucleic acid and ribonucleic acid synthesis, abnormalities in adenylyl
      cyclase cascade, and neurobehavioral effects (Johnson DE, et al. Brain Res Bull
      1998, pp 143-47; Lassiter TL, et al. Toxicol Sci 1999, pp 92-100; Chakraborti TK,
      et al. Pharmacol Biochem Behav 1993, pp 219-24; Whitney KD, et al. Toxicol Appl
      Pharm 1995, pp 53-62; Chanda SM, et al. Pharmacol Biochem Behav 1996, pp 771-76;
      Dam K, et al. Devel Brain Res 1998, pp 39-45; Campbell CG, et al. Brain Res Bull
      1997, pp 179-89; and Xong X, et al. Toxicol Appl Pharm 1997, pp 158-74
      [references 8-15, respectively, herein]). Furthermore, the terata caused by
      thalidomide is a graphic human example in which the animal model and timing of
      exposure were key factors (Parman T, et al. Natl Med 1999, pp 582-85; and Brenner
      CA, et al. Mol Human Repro 1998, pp 887-92 [references 16 and 17, respectively,
      herein]). Thus, it appears that more sensitive endpoints (e.g., enzyme activity,
      generation of reactive oxygen species, timing of exposure) for the measurement of
      toxic effects of environmental agents on embryos, fetuses, and neonates are more
      coherent than are gross terata observations. The perinatal period from the end of
      organogenesis to the end of the neonatal period in humans approximates the 28th
      day of gestation to 4 wk postpartum. Therefore, researchers must investigate
      similar stages of development (e.g., neurogenesis occurs in the 3rd trimester in
      humans and neonatal days occur during days 1-14 in rats and mice, whereas guinea
      pigs behave more like humans). Finally, screening for teratogenic events should
      also include exposure of females before mating or shortly following mating. Such
      a regimen is fruitful inasmuch as environmental agents cause adverse effec

PMID- 11572274
TI  - Brain cancer risk and electromagnetic fields (EMFs): assessing the geomagnetic
      component.
AB  - Cancer cluster studies in North Carolina identified several communities in which
      there existed an elevated risk of brain cancer. These findings prompted a series
      of case-control studies. The current article, which originated from the results
      of the 3rd of such studies, is focused on inclusion of the earth's own
      geomagnetic fields that interact with electromagnetic fields generated from
      distribution power lines. This article also contains an assessment of the
      contribution of confounding by residential (e.g., urban, rural) and case
      characteristics (e.g., age, race, gender). Newly diagnosed brain cancer cases
      were identified for a 4-county region of central North Carolina, which the
      authors chose on the basis of the results of earlier observations. A 3:1 matched
      series of cancer cases from the same hospitals in which the cases were diagnosed
      served as the comparison group. Extensive geographic information was collected
      and was based on an exact place of residence at the time of cancer diagnosis,
      thus providing several strategic geophysical elements for assessment. The model
      for this assessment was based on the effects of these two sources of
      electromagnetic fields for an ion cyclotron resonance mechanism of disease risk.
      The authors used logistic regression models that contained the predicted value
      for the parallel component of the earth's magnetic field; these models were
      somewhat erratic, and the elements were not merged productively into a single
      statistical model. Interpretation of these values was difficult; therefore, the
      modeled values for the model elements, at progressive distances from the nearest
      power-line segments, are provided. The results of this study demonstrate the
      merits of using large, population-based databases, as well as using rigorous
      Geographic Information System techniques, for the assessment of ecologic
      environmental risks. The results also suggest promise for exposure classification
      that is compatible with the theoretical biological mechanisms posited for
      electromagnetic fields.

PMID- 11572275
TI  - Dietary and clastogenic factors in children who immigrated to Israel from regions
      contaminated by the Chernobyl accident.
AB  - The authors evaluated the possible association between dietary history and plasma
      clastogenic factors in children who immigrated to Israel between 1989 and 1993
      from regions contaminated by the Chernobyl accident. The authors compared
      questionnaire data about demographic variables, dietary histories before and
      after immigration occurred, and health status with clastogenic factor scores for
      162 immigrants. Logistic regression analysis revealed a negative association
      between clastogenic factor scores and frequency of consumption of fresh
      vegetables and fruit among children < or = 7 yr of age during the postimmigration
      period. Intake of eggs and fish by boys who were < or = 7 yr of age prior to
      immigration was associated positively with clastogenic factor scores. Consumption
      of fresh vegetables and fruits afforded protection to the immune systems of
      children who were < or = 7 yr of age.

PMID- 11572276
TI  - Short-term effects of air pollution on mortality in the cities of Rouen and Le
      Havre, France, 1990-1995.
AB  - In this study, the authors examined the short-term effects of ambient air
      pollution on mortality across 2 French cities: Rouen and Le Havre. In Poisson
      regression models, which controlled for day-of-week effects, the authors used
      nonparametric smoothing to control for temporal trend, weather, and influenza
      epidemics. In Rouen, an interquartile range increase of 60.5-94.1 microg/m3 of
      ozone was associated with an increase of 4.1% (95% confidence interval = 0.6,
      7.8) of total mortality. Daily variations in sulfur dioxide (interquartile range
      increase = 17.6-36.4 microg/m3) were also associated with an 8.2% increase (95%
      confidence interval = 0.4, 16.6) in respiratory mortality. An increase of 6.1%
      (95% confidence interval = 1.5, 10.9) of cardiovascular mortality was also
      observed with an interquartile range increase of nitrogen dioxide (i.e., 25.3
      42.2 microg/m3). With respect to Le Havre, an interquartile range increase in
      daily levels of sulfur dioxide (11.3-35.6 microg/m3) was associated with an
      increase of approximately 3% (95% confidence interval = 0.8, 5) of cardiovascular
      mortality. For particulate matter less than or equal to 13 microm in diameter
      (interquartile increase = 21.5, 45.4 microg/m3), an increase of 6.2% (95%
      confidence interval = 0.1, 12.8) was observed. The estimates of pollutant effects
      and their standard deviations were slightly affected by the degree of smoothing
      temporal variations in this study. When low collinearity was present, the 2
      pollutant models provided acceptable estimates of pollutant effects. They
      suggested that the ozone effect was independent of the Black Smoke effect, and
      that the effects of sulfur dioxide and nitrogen dioxide were unlikely to be
      confounded by ozone concentrations. However, high collinearity leads to large
      estimates of the pollutant coefficient variances and, therefore, leads to
      inaccurate estimates of pollutant effects. The analysis of the contributory
      effects of different pollutant mixtures requires further investigation in those
      instances in which high collinearity between pollutants is present.

PMID- 11572277
TI  - Relationships between nitrogen dioxide personal exposure and ambient air
      monitoring measurements among children in three French metropolitan areas: VESTA
      study.
AB  - In epidemiological studies, investigators have routinely used ambient air
      concentrations, measured by air-quality monitoring networks, to assess exposure
      of subjects. When there is great spatial variability of ambient air
      concentrations or when there are specific indoor exposures, this approach may
      yield substantial exposure misclassification and distort the associations between
      exposure and the health endpoints of interest. In 3 French metropolitan areas,
      the cross-sectional relationships between 48 hr of nitrogen dioxide personal
      exposure of 73 children and the corresponding 48-hr background ambient air
      concentrations were analyzed. The crude correlation between ambient air
      concentrations and personal exposures was poor in all cities (r2 = .009 for
      Grenoble, r2 = .04 for Toulouse, and r2 = .02 for Paris). These correlations were
      improved when the authors took into account other ambient air or indoor air
      sources of nitrogen dioxide emissions (the corresponding multiple linear
      regression, r2, increased to .43 in Grenoble, .50 in Toulouse, and .37 in Paris).
      The main variables that explained personal exposures were an index of traffic
      intensity and proximity and use of a gas cooker at home. The results of this
      study confirm that ambient air-monitoring site measurements are poor predictors
      of personal exposure. Investigators should carefully characterize the proximity
      of roads occupied by dense traffic to the home/school as well as indoor sources
      of nitric oxide emissions; both of these careful characterizations will assist
      researchers in the prediction of personal exposure in epidemiological studies.

PMID- 11572278
TI  - Cancer risk associated with residential proximity to industrial sites: a review.
AB  - In this study, the authors sought to review available epidemiologic studies of
      cancer risk and its association with residence in a neighborhood characterized by
      industrial sites and to discuss options for future study design. The authors
      attempted to identify all case-control studies published from January 1980
      through July 1997 in which investigators examined exposure resulting from
      residential proximity to an industrial site neighborhood relative to an increased
      risk of lung, urinary tract, and lymphohematopoietic malignancies. During these
      years, some authors reported significant associations between lung cancer risk
      and residential proximity to (a) smelters, (b) complex industrial areas, and (c)
      other localized emission sources. There was some evidence that leukemia and
      lymphomas occurred in the neighborhoods that contained industrial sites.

PMID- 11572280
TI  - Declining trends of male proportion at birth in Europe.
AB  - Declining trends in male proportion at birth observed in several Western
      countries might reflect widespread exposure to pollutants capable of interfering
      with human reproduction. In this study, the authors describe male live birth
      proportion trends in 23 European countries from 1950 to 1996 (total of 305
      million live births). Overall, there was a significant linearly decreasing trend
      of 10 fewer males per 100,000 births each year, resulting in a loss of 73,462
      boys during a 47-yr period. The proportion of male births during the first 3 yr
      of the study period was higher than in the last 3 yr in 18 countries (i.e., 78%).
      Decreasing trends, which varied in slope and shape, were observed in 11
      countries; no significant trend was found in 8 countries, and male birth
      proportion increased in 4 countries. The results of this study confirmed that the
      proportion of male births is declining in Europe, and differences exist by region
      and country. Social and cultural aggregations of countries with decreasing trends
      suggest that sociodemographic characteristics might be more likely to explain
      trends than environmental exposures to chemicals. Investigators should evaluate
      this hypothesis to assess the usefulness of male birth proportion as a sentinel
      event.

PMID- 11572279
TI  - Exposure of the Inuit population of Nunavik (Arctic Quebec) to lead and mercury.
AB  - The authors conducted a survey during 1992 to evaluate blood levels of lead and
      mercury in Inuit adults of Nunavik (Arctic Quebec, Canada). Blood samples
      obtained from 492 participants (209 males and 283 females; mean age = 35 yr) were
      analyzed for lead and total mercury; mean (geometric) concentrations were 0.42
      micromol/l (range = 0.04-2.28 micromol/l) and 79.6 nmol/l (range = 4-560 nmol/l),
      respectively. Concentrations of omega-3 fatty acid in plasma phospholipids--a
      biomarker of marine food consumption--were correlated with mercury (r = .56, p <
      .001) and, to a lesser extent, with blood lead levels (r = .31, p < .001).
      Analyses of variance further revealed that smoking, age, and consumption of
      waterfowl were associated with lead concentrations (r2 = .30, p < .001), whereas
      age and consumption of seal and beluga whale were related to total mercury levels
      (r2 = .30, p < .001). A significant proportion of reproductive-age women had lead
      and mercury concentrations that exceeded those that have been reportedly
      associated with subtle neurodevelopmental deficits in other populations.

PMID- 11572281
TI  - Effects of temperature and humidification in the office environment.
AB  - In this investigation, the authors evaluated the relationship between temperature
      and (a) Sick Building Syndrome symptoms and (b) workers' perceptions of air
      dryness in environments with and without humidification. The authors studied the
      average intensity of symptoms and perceptions of dry air relative to room
      temperature in humidified and nonhumidified conditions. During the 6 wk of the
      experiment, 2 wings of the building were humidified one-by-one for 1 wk, followed
      by a week without humidification. A total of 230 daily questionnaires were
      completed during the nonhumidified period, and 233 were completed during the
      humidified period. The results were analyzed with linear regression analysis, and
      the average intensity of dryness symptoms and sensations of dryness increased
      with each unit increase in temperature above 22 degrees C, both in the humidified
      and nonhumidified conditions. Sick Building Syndrome symptoms increased relative
      only to temperature during the period of no humidification. In conclusion,
      temperatures above 22 degrees C caused increased dryness symptoms and a sensation
      of dryness, independent of humidification. The overall intensity of Sick Building
      Syndrome symptoms increased only when indoor air was not humidified.

PMID- 11572282
TI  - Recurrent diarrhea in children living in areas with high levels of nitrate in
      drinking water.
AB  - Given that there was documented evidence of an association between diarrhea and
      high nitrate ingestion, the authors examined drinking water nitrate concentration
      and its possible correlation(s) with methemoglobin levels, cytochrome b5
      reductase activity, and recurrent diarrhea. In addition, the authors studied
      histopathological changes in the intestines of rabbits in an animal model. Five
      village areas were studied, and nitrate concentrations (expressed in mg of
      nitrate per liter of water) of 26, 45, 95, 220, and 459 existed in the respective
      villages. The study included 88 randomly selected children who were 8 yr of age
      or younger; they represented 10% of the total population of each of the areas.
      Detailed histories of recurrent diarrhea were noted, and medical examinations
      were conducted. Cytochrome b5 reductase activity and methemoglobin levels were
      estimated biochemically. Collected data were analyzed statistically with
      Microsoft Excel software. In addition, the authors exposed rabbits to various
      levels of nitrate, and histopathological changes of the stomach and intestine
      (small and large) were evaluated. There was a strong relationship between nitrate
      concentration and recurrent diarrhea; 80% of the recurrent diarrhea cases were
      explained by nitrate concentration alone. In the rabbit intestines, lymphocytic
      infiltration and hyperplasia characterized the submucosa as nitrate
      concentrations increased.

PMID- 11572283
TI  - The German Environmental Survey 1990/92 (GerES II): primary predictors of blood
      cadmium levels in adults.
AB  - As part of the representative Environmental Survey in Germany in 1990-1992,
      investigators determined cadmium levels in blood provided by 3,965 subjects aged
      25-69 yr. The investigators considered approximately 150 variables (i.e.,
      demographics, household and occupational characteristics, environmental
      exposures, smoking habits, frequency of food consumption, and additional life
      style features) as potential predictors in multivariate regression analysis. On
      the basis of the results of multivariate regression analysis, the authors derived
      2 slightly different models for the prediction of blood cadmium levels in
      populations from West and East Germany. Both models included 3 primary predictors
      of blood cadmium levels. The 2 models explained 51.3% and 61.2% of the observed
      variance in blood cadmium levels in West and East Germany, respectively. The most
      important predictor was a specific indicator for smoking habits, which was
      determined from a separate mathematical model. In this model, the effect of
      smoking was considered, and the model accounted for the biological half-life of
      cadmium in blood.

PMID- 11572284
TI  - Distribution of volatile organic compounds in ambient air of Tehran.
AB  - Transportation sources have created a major hydrocarbon pollution problem in the
      ambient air of Tehran. The authors used a Carbotrap tube to determine volatile
      organic compounds in air. Such compounds can be desorbed thermally and analyzed
      with gas chromatography-mass spectrometry. Samples were obtained from 8 sites in
      Tehran at which traffic flow varied between 500 and 2,500 vehicles/hr. A total of
      54 hydrocarbons were identified in the ambient air of Tehran, and the average
      measured concentrations of benzene, toluene, m- and p-xylene, ethyl benzene, and
      o-xylene were 127.6 microg/m3, 201.1 microg/m3, 110.7 microg/m3, 58.1 microg/m3,
      and 57.6 microg/m3, respectively (standard deviation = 3.8-51.7 microg/m3).
      Emissions of individual pollutants in south Tehran exceeded those in north
      Tehran, and these emissions were higher during the afternoon than during the
      morning. The geographical parameters and the photochemical reaction also played
      important roles in the pollution conditions.

PMID- 11572285
TI  - A model for clinical evaluation of the effect of antimicrobial agents on carious
      dentin.
AB  - PURPOSE: To evaluate, longitudinally, the effect of a chlorhexidine varnish on
      the proteolytic activity of dentin caries in vivo. MATERIALS AND METHODS: 20
      permanent molars and 8 primary molars with carious lesions in dentin were studied
      in subjects 18-35 yrs old (n=20), and 5-6 yrs old (n=8) respectively. These
      lesions were clinically evaluated according to texture and color. Carious dentin
      specimens were obtained by means of biopsies performed with a #4 carbide bur at
      the initial visit (TO) before application of a 10% chlorhexidine varnish and 2,
      4, 8, and 12 wks thereafter. The dentin biopsies were immersed in Sorensen's
      buffer, vortexed for 30 s, and mixed with a 1.67 mM solution of n-benzoyl-DL
      arginine-naphthylamide (BANA), a substrate for proteolytic enzymes. Samples were
      incubated overnight at 37 degrees C and color was developed with 0.1% fast
      garnet. The optical density (OD) of reaction mixtures was recorded
      photometrically. All teeth were grouped for analysis, as Mann-Whitney tests
      revealed no statistically significant differences between median values for OD
      for both age groups. ANOVA was used to compare progressive inhibition of
      proteolytic activity in dentin caries samples over time. RESULTS: The average
      proteolytic activity at the dentin substrates (OD) at TO and 2, 4, 8 and 12 wks
      thereafter were 0.794+/-0.089, 0.741+/-0.071, 0.676+/-0.087, 0.600+/-0.094, and
      0.508+/-0.108 respectively. The chlorhexidine varnish mediated a significant
      inhibition of the proteolytic activity present in dentin caries after 12 wks
      (P<0.0001). At T0, 100% of the carious lesions examined were characterized as
      soft upon exploration. After 12 wks, 54% (15/28) of the lesions were partially
      hardened and 46% (13/28) hardened/nonprogressing. The dentin color was
      yellow/light brown in 100% of the lesions at baseline, and dark brown/black in
      86% (24/28) after 12 wks. CLINICAL SIGNIFICANCE: This study demonstrated that
      chlorhexidine varnishes arrested active caries in vivo and inhibited the
      proteolytic activity present in these lesions. These findings strengthen the
      rationale for including chlorhexidine in the overall treatment strategy for
      patients with high caries activity.

PMID- 11572286
TI  - Safety of three toothbrushes.
AB  - PURPOSE: To assess the oral soft tissue safety and tolerability of two electric
      toothbrushes, the Crest Spin Brush and Colgate ActiBrush, and one manual
      toothbrush, the Oral B 40. MATERIALS AND METHODS: A total of 104 subjects were
      enrolled in this single center, randomized, examiner-blind parallel study over a
      4-wk test period. Subjects were randomized to treatment and were instructed to
      brush in their normal manner, twice per day for 60 s. A detailed oral soft tissue
      examination and interview were conducted by a trained clinician at baseline, 3
      days and 4 wks to assess clinical signs and symptoms associated with use of the
      toothbrushes. RESULTS: Over the 4-wk period, a total of 19 subjects (18% of the
      study population) were observed for signs/symptoms. The adverse events were
      distributed across test groups with 12 subjects in the Oral B 40 group, 4
      subjects in the Crest Spin Brush group, and 3 subjects in the Colgate ActiBrush
      group experiencing at least one adverse event. All adverse events were mild in
      severity indicating the general safety of all three toothbrushes. The most
      frequently encountered event was localized gingivitis. The Oral B 40 test group
      was observed with more adverse events when compared to the Crest Spin Brush and
      Colgate ActiBrush at 4 wks but not at 3 days. The proportion of subjects
      experiencing an adverse event in the Crest Spin Brush test group was similar to
      that of Colgate ActiBrush group. All three toothbrushes were generally well
      tolerated by subjects enrolled in the study with the Crest Spin Brush and Colgate
      ActiBrush being the best tolerated. CLINICAL SIGNIFICANCE: The results of this
      study indicated that abnormal oral soft tissue findings were distributed among
      the treatment groups, indicating that daily use of an electric toothbrush is at
      least as safe as a manual toothbrush.

PMID- 11572287
TI  - Fissure sealing: optimization of sealant penetration and sealing properties.
AB  - PURPOSE: This in vitro study determined the penetration depth of a fissure
      sealant into an empty fissure system and into a conditioned enamel surface, using
      different sealing procedures. MATERIALS AND METHODS: 48 extracted, non-carious
      human molars were sealed with the unfilled sealant (Heliobond) using the enamel
      adhesive technique (35% phosphoric acid gel, 120 s etching time, bond
      application, light-curing for 60 s). The following factors were tested in
      comparison to the control group (1): influence of a precuring time lapse of 20 s
      after sealant application (2); ultrasound application with a plastic tip during
      the etching procedure (3); a wetting agent in an acid vehicle (4); enamel drying
      with acetone after the etching procedure (5); and finally, the combination of
      ultrasound during etching; a drying procedure with acetone; and a 20 s precuring
      time lapse (all applied to the same sample). The sealed teeth were sectioned and
      evaluated by conventional light microscopy to determine the penetration depth
      into the fissure, and by confocal laser microscopy to investigate the quality of
      the adhesion zone. RESULTS: Strict adherence to a specified penetration time, an
      intensified etching procedure with ultrasound, and the use of a drying procedure
      with acetone each showed a positive effect on the fissure penetration depth of
      the sealant and on the adhesion zone. The combination of these measures improved
      significantly the quality of the fissure sealing. Penetration depth increased to
      92% of the fissure depth. From 95-100% of the total length of the analyzed
      adhesion zone shows excellent tags of sealant in the conditioned enamel surface.
      CLINICAL SIGNIFICANCE: Simple changes in the application technique of fissure
      sealants, such as ultrasonic treatment during etching procedure and drying the
      etched fissure system by acetone, improved the quality of the fissure sealing,
      which is a noninvasive preventive measure.

PMID- 11572288
TI  - Effect of composite resin placement techniques on the microleakage of two self
      etching dentin-bonding agents.
AB  - PURPOSE: To evaluate microleakage of Class V resin-based composites (RBC) bonded
      with two self-etching dentin adhesive systems. Class V cavities were restored
      with either one or three increments of RBC to determine whether the restorative
      method affected microleakage. MATERIALS AND METHODS: 60 extracted human premolars
      and molars were randomly assigned to 6 groups for bonding with Clearfil Liner
      Bond 2V or Etch & Prime 3.0 or Prime & Bond NT. The latter, using a total-etch
      technique, was used as a control. Cavities were cut in both the buccal and
      lingual surfaces. Half of each preparation was in enamel and half was in
      cementum/dentin. The teeth were thermocycled and the restorations examined
      microscopically for leakage using Procion Brilliant Red as a marker. SEM
      microphotographs were prepared from dye-labeled and non dye-labeled areas to
      illustrate the micromorphology of the systems. RESULTS: None of the groups showed
      microleakage at the enamel margins. All groups showed microleakage at the
      gingival margins. At the gingival margin, there was no significant difference
      between the groups irrespective of the bonding material (Kruskal-Wallis: ANOVA
      P=0.2113). No significant difference was observed with each material when the
      bulk filling (one increment) technique was compared with the three-increment
      technique. SEM showed that the self-etching materials produced a shallower depth
      of etch, and a less abundant resin tag complex than the material using a separate
      phosphoric acid gel. In dye-labeled areas, debonding was predominantly cohesive
      in resin. CLINICAL SIGNIFICANCE: Gingival margin microleakage is not prevented 
      by either restoring cavities with self-etching materials of the control using a
      total-etch technique.

PMID- 11572289
TI  - Effects of restorative and adhesive curing methods on dentin bond strengths.
AB  - PURPOSE: To evaluate the shear bond strengths of "one-bottle" adhesives to dentin
      when used with self-cured composite. MATERIALS AND METHODS: 100 bovine teeth were
      ground to expose superficial dentin, which was polished to 600-grit. The dentin
      was etched for 15 s with 35% phosphoric acid, rinsed, and blotted with tissue
      paper. The surface remained visibly moist for all specimens. The following
      adhesives were applied to the etched dentin according to manufacturers'
      directions: Scotchbond Multi-Purpose (in its visible light-cured [VLC] and self
      cure modes) as a control, One-Step (VLC only), OptiBond Solo Plus (VLC only),
      Prime & Bond NT (VLC) and Prime & Bond NT Dual-Cure. For each adhesive, specimens
      were bonded with a self-cure composite, while 10 were bonded with a VLC composite
      as a control. After 24 hrs water storage, shear bond strengths were determined
      using an Instron universal testing machine. Data were analyzed using two-way
      ANOVA, Tukey's test, and Student's t-tests. RESULTS: Using the light-cured
      composite, mean bond strengths ranged from 11.0 MPa for light-cured Prime & Bond
      NT to 26.3 MPa for OptiBond Solo Plus. Using the self-cure composite, mean bond
      strengths ranged from 0.0 for light-cured Prime & Bond NT to 21.4 MPa for One
      Step. Two adhesives, light-cured Prime & Bond NT and OptiBond Solo Plus, had
      significantly lower bond strengths when used with the self-cure composite.
      CLINICAL SIGNIFICANCE: Some "one-bottle" dentin adhesives may not provide
      acceptable bonding to tooth structure when they are used with self-cure
      composites.

PMID- 11572290
TI  - Two-year composite/dentin bond stability.
AB  - PURPOSE: To examine the composite-to-dentin shear bond strengths over 2 yrs of
      three chemically different single bottle dentin adhesives: water-based Syntac
      Single Component (SSC); acetone-based Prime & Bond 2.1 (PB), and; ethanol-based
      and filled OptiBond Solo (OS). MATERIALS AND METHODS: Extracted human molars
      stored in 0.2% sodium azide were randomly assigned to each of three dentin bond
      groups for testing at 5 time periods (n=15). The crowns of the teeth were
      sectioned to expose occlusal dentin and the roots embedded in acrylic. The dentin
      was etched with 37% H3PO4 for 20 s, rinsed and dentin adhesives applied per
      manufacturers' instructions. A column of Z-100 composite was bonded to the
      treated dentin surface and light cured. Teeth were stored in distilled water at
      37 degrees C and thermocycled for 1,000 cycles between 5 degrees C and 55 degrees
      C and tested in shear at 24 hrs (baseline), 6, 12, 18 and 24 months. Mean +/- SD
      shear bond strengths (SBS) were determined. RESULTS: ANOVA at a significance
      level of P< 0.05 revealed OS had significantly higher SBS at 6 and 12 months
      compared to baseline. PB had significantly higher SBS at 12 months compared to
      baseline. SSC had significantly higher SBV at 18 months compared to baseline.
      However, at 24 months the SBV for OS and SSC were significantly lower than at
      baseline. During all time periods, OS and PB had significantly higher SBS than
      SSC. CLINICAL SIGNIFICANCE: The long-term stability of resin-based composite to
      dentin bond strengths from single bond adhesives is questionable because after 2
      yrs, bond strengths for two of the three tested dentin adhesives, OptiBond Solo
      and Syntac Single Component, were significantly lower than initial strengths.

PMID- 11572291
TI  - Soft-start polymerization and marginal gap formation in vitro.
AB  - PURPOSE: To determine the effect of soft-start polymerization of resin-based
      composites on the marginal gap formation in dentin cavities. MATERIALS AND
      METHODS: Cylindrical cavities were prepared in dentin in extracted human molars.
      The cavities were distributed into 8 groups. The teeth in groups 1-4 were treated
      with Scotchbond Multi-Purpose and restored with Z100, and the teeth in groups 5-8
      were treated with OptiBond FL and restored with Herculite XRV. The restorations
      were light-cured for 40 s by four different curing modes. The marginal gap
      formation was measured in a light microscope after a 20 min water-storage, and
      the wall-to-wall contraction was calculated as the widest gap in percent of the
      cavity diameter. RESULTS: Soft-start light curing did not influence wall-to-wall
      contraction in dentin cavities. OptiBond FL and Herculite XRV showed less wall-to
      wall contraction than did Scotchbond Multi-Purpose and Z100. CLINICAL
      SIGNIFICANCE: The soft-start polymerization procedures studied did not improve
      the marginal adaptation of two resin composites bonded to dentin cavities
      compared with conventional polymerization.

PMID- 11572292
TI  - Three-year follow up assessment of Class II restorations in primary molars with a
      polyacid-modified composite resin and a hybrid composite.
AB  - PURPOSE: To evaluate the 3-year success rate of Class II restorations in primary
      molars performed with Compoglass, a polyacid-modified resin-based composite
      (compomer) and TPH-Spectrum, a hybrid resin-based composite. MATERIAL AND
      METHODS: In a dental practice, in each of 52 children at least two primary molars
      were restored. 96 primary molars were restored with TPH-Spectrum using the total
      etching-technique and 94 with Compoglass without acid etching prior to
      application of the bonding adhesive. The restorations were assessed at baseline
      (1996) and after 1 and 2 yrs according to the Ryge criteria. After 3 yrs the
      restorations (46 Compoglass, 46 TPH-Spectrum) of 35 children were re-evaluated.
      RESULTS: After 3 yrs the cumulative success rate according to the Kaplan-Meier
      estimation was 79.5% for the Compoglass and 85.8% for the TPH-Spectrum
      restorations. No significant differences were observed between the two materials
      with respect to color matching, cavosurface discoloration, anatomic form, margin
      integrity and caries assessment. The present investigation revealed that TPH
      Spectrum and Compoglass are suitable materials for restoring primary molars.
      CLINICAL SIGNIFICANCE: After an observation period of 3 years, both TPH-Spectrum
      and Compoglass demonstrated acceptable clinical results.

PMID- 11572293
TI  - Clinical performance of a resin-modified glass-ionomer and a compomer in
      restoring non-carious cervical lesions. 5-year results.
AB  - PURPOSE: To evaluate the 5-yr clinical performance of a resin-modified glass
      ionomer cement and a polyacid-modified resin composite in restoring non-carious
      cervical lesions. MATERIALS AND METHODS: Non-carious cervical lesions in 46
      incisors, canines, and premolars were restored either with Fuji II LC (n=18) or
      with Dyract (n=28) in 16 healthy patients. The lesions were restored without
      cavity preparation strictly according to the manufacturer's instructions. The
      restorations were clinically evaluated single blind after 5 yrs using modified
      USPHS criteria. RESULTS: The percentage of Alfa ratings were as follows
      (Dyract/Fuji II LC): color match 81.3%/28.6%, surface texture 93.8%/21.4%,
      anatomic form 75.0%/28.6%, marginal integrity (enamel) 62.5%/42.9%, marginal
      integrity (dentin) 68.8%/28.6%, marginal discoloration (enamel) 56.3%/42.9%,
      marginal discoloration (dentin) 68.8%/21.5%. Five-yr data revealed a significant
      difference between the clinical ratings of Dyract and Fuji II LC for all criteria
      except marginal integrity and marginal discoloration in enamel. A total of five
      Dyract restorations and four Fuji II LC restorations failed within the study
      period. CLINICAL SIGNIFICANCE: A considerably high and almost similar overall
      failure rate was found for both restorative materials in restoring non-carious
      cervical lesions. However, retained Dyract restorations presented superior
      clinical performance compared to Fuji II LC restorations.

PMID- 11572294
TI  - Cavity preparation devices: effect on microleakage of Class V resin-based
      composite restorations.
AB  - PURPOSE: To evaluate the effect of cavity preparation device (i.e. carbide bur,
      diamond bur, air abrasive, Sonicsys, and Er:YAG laser) on microleakage of Class V
      resin-based composite (RBC) restorations, the tooth restoration interface and
      dentin ultrastructure. MATERIALS AND METHODS: Eight groups (n=18) of 9 human
      molars each were prepared on the buccal and lingual surfaces for Class V RBC
      restorations using five preparation devices: Group 1: carbide bur #8 round; Group
      2: diamond bur #801; Group 3: KCP 1000 air abrasion unit; Group 4: Sonicsys
      Approx.; Group 5: Er:YAG laser; Group 6: carbide bur plus air abrasive; Group 7:
      carbide bur plus laser, and Group 8: laser without etching. Circular cavity
      preparations, 3 mm diameter and 1.5 mm deep, were cut at the CEJ on the buccal
      and lingual surfaces of each tooth. A bevel was placed on the enamel margin. All
      cavities were restored using Single Bond adhesive system and Silux Plus according
      to manufacturer's directions, with the exception that no etchant was used with
      Group 8. After thermocycling, specimens were tested for microleakage using silver
      nitrate methodology. Dye penetration data was collected and subjected to non
      parametric statistical analysis. SEM analysis of the dentin-RBC interface, as
      well as the effect of each cavity preparation device on the surface of dentin was
      performed. RESULTS: Microleakage did not occur in enamel for any method of cavity
      preparation when the enamel was etched prior to adhesive application. Kruskal
      Wallis One-way ANOVA revealed differences in dentin microleakage among the tested
      groups at alpha=0.05. Mann-Whitney Test for Paired Comparisons at alpha=0.01
      demonstrated significantly greater dentin microleakage in Groups 5 and 7 compared
      to all groups except Group 3 (air abrasive). Although Group 8 had the least
      microleakage in dentin, this was not significantly different from Groups 1, 2, 4
      and 6. SEM observation revealed hybridization at the dentin-resin interface for
      all groups except for Group 8 (laser prepared, non-etched). Surface analysis
      showed differences related to the operating mode of each preparation device.
      CLINICAL SIGNIFICANCE: The method of cavity preparation did not affect
      microleakage in etched enamel. When using a laser for cavity preparation, enamel
      should be etched although not etching dentin may help to improve marginal seal.

PMID- 11572295
TI  - Microleakage of self-etching primers after thermal and flexural load cycling.
AB  - PURPOSE: To evaluate the adhesive properties of a one-bottle self-etching primer
      system. MATERIALS AND METHODS: 150 wedge-shaped cervical cavities on bovine teeth
      were restored with Clearfil Liner Bond 2 (LB), Clearfil Liner Bond 2V (LV) or
      Clearfil SE Bond (SE), according to the manufacturer's instructions. Twenty
      specimens of each adhesive system were finished 15 mins after light curing and 30
      specimens were finished after a 24-hr storage period in water. From each group,
      10 restorations were immediately immersed in 0.5% basic fuchsin solution and kept
      there for 24 hrs to examine microleakage. The other 10 restorations were
      thermocycled (5-60 degrees C, 15 s dwell time, 5,000 cycles), and then immersed
      in the dye solution. The remaining 10 specimens of the 24-hr storage group were
      subjected to flexural load cycling (0.5 mm labio-lingual displacement at the
      incisal edge, 10,000 cycles, 1 cps) prior to immersion in the dye solution. The
      data was analyzed using the Mann-Whitney U-test and the Kruskal-Wallis test. The
      tensile bond strengths of the adhesive systems to bovine enamel and dentin were
      also determined. The data was analyzed using the Student's t-test and ANOVA. In
      addition, SEM examinations were made to evaluate the effects of self-etching
      primers on enamel and dentin surfaces. RESULTS: LV and SE showed significantly
      better marginal sealing than LB (P<0.05). The marginal integrity of SE did not
      deteriorate even after immediate finishing, thermal stresses or flexural loads.
      There were no significant differences in bond strengths among the adhesive
      systems tested. All adhesive systems showed similar bond strengths to enamel and
      dentin. The enamel etching patterns using LV and SE systems were obscure and
      difficult to assess. Although the smear plugs were not fully removed, no smear
      layer was observed on the treated dentin surfaces, regardless of the self-etching
      primer system used. CLINICAL SIGNIFICANCE: Clearfil SE bond could possibly
      improve the clinical performance of cervical cavities.

PMID- 11572296
TI  - Microleakage of adhesive restorative materials.
AB  - PURPOSE: To compare the marginal sealing ability of two conventional and one
      polyacid-modified resin-based composite, and two conventional and three resin
      modified glass-ionomers in conventional cylindrical box cavities following a
      silver-staining microleakage evaluation method. MATERIALS AND METHODS: In 80
      freshly extracted and caries-free human third molars, three standardized
      cylindrical butt-joint cavities were prepared: the first cavity in coronal
      enamel, the second at the cemento-enamel junction (CEJ) and the third completely
      in root cementum. A control group of 10 additional teeth was chosen. After the
      cavities were restored randomly using the eight restorative materials tested, the
      specimens were first stored in distilled water at 37 degrees C for 7 days and
      then thermocycled (500 cycles). Thereafter, the specimens were centrifuged for 10
      min in plastic bottles containing 50 wt% silver nitrate aqueous solution. The
      degree of microleakage was recorded at four different depths along the
      restoration margins using an optical stereomicroscope equipped with a measuring
      gauge. RESULTS: None of the tested systems prevented microleakage completely, but
      the extent of leakage decreased towards the bottom of the restorations. The resin
      modified glass-ionomers performed better than the conventional resin-based
      composites and conventional glass-ionomers. CLINICAL SIGNIFICANCE: Distinct
      leakage patterns were recorded among all materials investigated.  Complete
      marginal sealing could still not be reached with the new adhesive restorative
      materials.

PMID- 11572297
TI  - Microleakage of Class II composite restorations.
AB  - PURPOSES: (1) To evaluate the in vitro sealing ability of several Class II resin
      restorations whose gingival extension of the proximal margin was apical to the
      cemento-enamel junction and in dentin and (2) to determine the effect of
      thermocycling on leakage into the resin-tooth interface. MATERIALS AND METHODS:
      Mesio-occlusal and distoocclusal preparations were made in extracted human
      molars. The gingival floor of the proximal box, was placed 1.0mm apical to the
      CEJ, and was prepared to a width of 1.5mm from the cavosurface margin to the
      axial wall. The teeth were restored with one of seven restorations (Z100 control,
      Z100, Wave, F2000, Surefil, Z100 and Vitrebond Sandwich A, Z100 and Vitrebond
      Sandwich B) using multiple incremental placement and materials. Following
      storage, half the samples were thermocycled. All 70 samples were stained using
      silver nitrate. The entire resin restoration was then removed from the proximal
      box ,and starting at the cavosurface margin the gingival floor was divided into
      three zones of 0.5 mm each and analyzed for dye penetration, using a novel
      technique which utilized the aid of computer imaging software and assessed both
      quantitatively and qualitatively. RESULTS: There was no statistical difference in
      leakage for all groups in Zone 1. For Zones 2 and 3, the groups utilizing glass
      ionomer liner on the cavosurface margin had significantly less microleakage
      (P>0.05). Although the compomer/hybrid combination had low leakage values on
      average, the wide range of values led to unpredictable results. The
      flowable/hybrid combination and the packable composite performed less favorably.
      CLINICAL SIGNIFICANCE: This study demonstrated the difficulty in sealing a
      proximal dentin margin.  However, the glass-ionomer/hybrid restorative techniques
      is the most likely to give successful clinical results.

PMID- 11572298
TI  - Additions to the OSHA bloodborne pathogens standard.

PMID- 11572299
TI  - Superficial mucoceles of the lower lip.

PMID- 11572300
TI  - Female adolescent friendship and delinquent behavior.
AB  - Young female offenders (n = 29) and female high school students (n = 47) were
      compared in terms of delinquent behavior and relationships with their best female
      friend and peer group. Young offenders exhibited significantly more delinquent
      behavior than did high school students in the past year. Delinquents and
      nondelinquents did not significantly differ in amount of companionship, conflict,
      help, security, and closeness with their best female friend, and amount of trust,
      alienation, and perceived intimacy in their peer group. Less communication and
      more perceived peer pressure in the peer group distinguished delinquent females
      from nondelinquent females. Perceived peer pressure significantly predicted
      delinquent behavior in female adolescents. In short, friendships of delinquent
      and nondelinquent female adolescents are essentially similar despite higher
      levels of peer pressure among delinquents.

PMID- 11572301
TI  - Predictors of depression in female adolescents.
AB  - Depression during adolescence has been associated with a number of factors,
      including failure to individuate (Blos, 1968), insecure attachments (Armsden,
      McCauley, Greenberg, Burke, & Mitchell, 1990), negative parental representations,
      and object relations that lack self-other differentiation (Blatt, Wein, Chevron,
      & Quinlan, 1979). The present study examined factors associated with symptoms of
      depression in 59 nonclinical female adolescents. Specifically, the relationship
      between a number of theoretically related measures-separation-individuation,
      interpersonal concerns, self-critical concerns, attachment style, parental
      representations-and symptoms of depression was investigated. The model developed
      was able to explain the interrelationships of the variables involved in the
      psychological process of adolescence, and their demonstrated ability to predict
      symptoms of depression in normal female adolescents.

PMID- 11572302
TI  - Parent, peer, and media influences on body image and strategies to both increase
      and decrease body size among adolescent boys and girls.
AB  - This study investigated the nature of body image and body change strategies, as
      well as the sociocultural influences on these variables, among a group of 1,266
      adolescents (622 males, 644 females). In particular, it investigated weight gain
      and increased muscle, as well as weight loss. It was found that females were less
      satisfied with their bodies and were more likely to adopt strategies to lose
      weight, whereas males were more likely to adopt strategies to increase weight and
      muscle tone. Respondents with higher body mass index (BMI) evidenced greater body
      dissatisfaction and more weight loss strategies, but there were no differences
      between BMI groups in weight gain or strategies to increase muscles. Weight gain
      and strategies to increase muscles were more likely to be undertaken by older
      adolescents, but there were no grade level differences in weight loss. Media
      influences to alter weight, as well as feedback from mother, father, and both
      male and female peers, were greater for females. There were few grade level or
      BMI differences in regard to any of the sociocultural influences. The importance
      of these findings in terms of providing a better understanding of factors which
      may lead to a disturbed body image and body change disorders, particularly among
      adolescent boys, is discussed.

PMID- 11572303
TI  - Adolescent suicidal ideation.
AB  - Adolescent suicidal ideation and its relationship to other variables was tapped
      by a self-report questionnaire administered to 88 high school seniors. Eighteen
      percent responded positively to the statement "sometimes I feel suicidal." Those
      who reported suicidal ideation were found to differ from those who did not on a
      number of variables, including family relationships (quality of relationship with
      mother, intimacy with parents, and closeness to siblings), family history of
      depression (maternal depression), peer relations (quality of peer relationships,
      popularity, and number of friends), emotional well-being (happiness, anger, and
      depression), drug use (cigarettes, marijuana, and cocaine), and grade point
      average. Stepwise regression indicated that happiness explained 46% of the
      variance in suicidal ideation, and number of friends, anger, and marijuana use
      explained an additional 20%, for a total of 66% of the variance. While 34% of the
      variance remained unexplained, it is suggested that the questions used to measure
      these four variables be included in global screenings to identify adolescents at
      risk for suicidal ideation.

PMID- 11572304
TI  - Help-seeking atititudes among Israeli adolescents.
AB  - This study investigated the willingness of Israeli adolescents to seek help for
      emotional and health problems, and their preference for various helping agents.
      Nearly fifteen hundred students in grades 7-12 participated in a comprehensive
      survey of attitudes, health status, and concerns, and the data were analyzed.
      Gender and age were identified as factors associated with help-seeking attitudes.
      Females reported a higher level of distress and greater willingness to seek help
      than did males. Younger adolescents tended to state that they would turn to
      parents for help, whereas older adolescents increasingly preferred peers. In
      general, the adolescents preferred to seek help from family and peers for
      emotional and social problems, rather than turning to professionals. Adolescents
      in grades 9-10 reported the highest level of distress and were least willing to
      seek help for interpersonal problems and depressed mood. Overall, level of
      distress was not directly related to willingness to seek help. In subgroups of
      depressed and suicidal adolescents, an inverse relationship was found between
      willingness to seek help and levels of depression and suicidal ideation.
      Recommendations for health care services and counseling programs are discussed.

PMID- 11572305
TI  - Examination of a model of multiple sociocultural influences on adolescent girls'
      body dissatisfaction and dietary restraint.
AB  - This study examined the perceived role of three types of sociocultural agents
      (peers, parents, and media) in influencing body dissatisfaction and dietary
      restraint in adolescent girls. Participants were 577 grade 10 girls from six
      schools who completed questionnaires in class and had height and weight measured.
      Two path analyses resulted in a similar pattern. While current body size strongly
      predicted ideal body size and body dissatisfaction, perceived influence of
      multiple sociocultural agents regarding thinness also had a direct relationship
      with body ideal and dissatisfaction. Dietary restraint was predicted directly
      from body dissatisfaction and sociocultural influences. Peers, parents, and media
      varied in their perceived influence. The findings support the idea that those
      girls who show the most body dissatisfaction and dietary restraint live in a
      subculture supporting a thin ideal and encouraging dieting.

PMID- 11572306
TI  - Adolescents' perceptions of discipline within intact families and stepfamilies.
AB  - This study examined adolescents' perceptions of discipline in intact families and
      stepfamilies. Forty-five adolescents, ranging in age from 15 to 19 years,
      completed the Adolescent Discipline Perception Survey (ADPS). They responded to
      questions related to their own discipline experiences as well as their views on
      how they would discipline an adolescent. Results indicated that adolescents from
      intact families and stepfamilies identified loss of privileges and grounding as
      the primary discipline methods used by their families. In addition, adolescents
      from intact families and stepfamilies reported house rules and peers as the most
      common discipline issues. Twenty-six percent of adolescents from intact families
      and 44% of those from stepfamilies reported that grounding was the most severe
      form of punishment they had received.

PMID- 11572307
TI  - Internal poverty and teen pregnancy.
AB  - The subjects for the present study were drawn from the female students who
      participated in the National Education Longitudinal Study (NELS) initial eighth
      grade data collection. Adolescent females who later became pregnant were matched
      on race, birth month, and birth year with adolescent females who did not report a
      pregnancy. The study examined selected predictor variables from the baseline 1988
      wave of data in relation to the outcome variable of pregnancy status. Results
      indicated a statistically significant difference in locus of control between
      those females who later became pregnant and those who later did not experience a
      pregnancy during adolescence. Those who later became pregnant were much more
      likely to have an external locus of control (p = .0001). Females who later became
      pregnant were also more likely to have a poorer sense of personal efficacy (p =
      .0001). Finally, females who later experienced a teen pregnancy had more
      traditional occupational expectations (p = .006) and lower educational
      expectations (p = .001) than did those who did not later report a teen pregnancy.

PMID- 11572308
TI  - Parents' attitudes and expectations regarding science education: comparisons
      among American, Chinese-American, and Chinese families.
AB  - This study examined the differences in attitudes toward science education among
      American, Chinese-American, and Chinese parents and students. Parents'
      expectations for their high school children's science performance were also
      compared among the three cultural groups. It was found that both Chinese parents
      and students had more positive attitudes toward science education than did their
      American counterparts. Chinese parents placed greater emphasis on self
      improvement, set higher standards, and more often helped their children to learn
      science than did American parents. The attitudes of the Chinese-Americans
      appeared to show the influences of both their Chinese heritage and American
      culture. Overall, a high positive correlation was found between parents' and
      students' attitudes toward science education.

PMID- 11572309
TI  - Body weight, self-esteem, and depression in Korean female.
AB  - The purpose of this study was to examine whether body mass index (BMI) and
      perception of a body weight problem predict level of self-esteem and depression
      in Korean female adolescents. The sample consisted of 303 females, ranging in age
      from 15 to 19 years, who were attending four high schools located in Seoul,
      Korea. BMI and desired BMI were calculated based on self-reported weight and
      height. Self-perception of having a weight problem was evaluated by one question:
      "Do you see yourself as having a weight problem?" Self-esteem was measured using
      the Rosenberg Self-Esteem Scale, and depression was measured using the Center for
      Epidemiologic Studies Depression Scale. Based on BMI, 18.2% of the females were
      underweight, 79.2% were of normal weight, and 2.6% were overweight. Based on
      desired BMI, 78.5% of the females desired to be underweight. Results showed that
      perception of a weight problem, but not BMI, contributed significantly to the
      prediction of level of self-esteem and depression. In addition, there was a
      significant positive correlation between BMI and perception of a weight problem.

PMID- 11572310
TI  - Mental health problems and symptoms among male adolescents attending a teen
      health clinic.
AB  - The purpose of this study was to examine the frequency and nature of mental
      health problems and symptoms among a group of 51 inner-city male adolescents
      attending a teen health clinic at a large county hospital in the southwestern
      part of the United States. They were administered a problem area checklist and a
      problem symptom checklist. The problem area checklist covered a range of mental
      health issues, including peer/friendship, relationship, and family problems;
      problems with money, time, and the law; substance use; and eating disorders. The
      problem symptom checklist queried participants about anger, nervousness,
      depression, fear, loneliness, suicide, aggression, and self-esteem. The results
      indicated that these young males experienced significant mental health problems
      and symptoms, such as relationship problems, problems with time and money, and
      symptoms of anger, depression, and aggression. Further, scared/afraid feelings
      correlated with five of the eight problem areas. The authors recommend
      investigating ways to target young males who present at such clinics in order to
      address their mental health problems and symptoms, as well as studying how their
      environment affects their overall health.

PMID- 11572311
TI  - The relationship between adolescent attitudes towards authority, self-concept,
      and delinquency.
AB  - Attitudes towards authority of youth and adults have been investigated in recent
      years in a number of Western countries. The present research focused on attitudes
      towards institutional authority among three groups of adolescents:
      nondelinquents, noninstitutionalized delinquents, and institutionalized
      delinquents. Relationships with self-concept were also investigated. It was found
      that attitudes towards parents, teachers, police, and the law were, in general,
      positive. Nondelinquents' attitudes were more positive than those of delinquents.

PMID- 11572312
TI  - Adolescents' reactions to hypothetical peer group conversations: evidence for an
      imaginary audience?
AB  - The theory of adolescent egocentrism holds that early adolescents have a
      distorted understanding of self-other relations; because of flaws in the
      traditional methods used to assess adolescent egocentrism, this notion has never
      received adequate empirical scrutiny. In the present research, the nature of
      early adolescent social cognition as characterized by that theory was
      investigated by examining age differences in judgments of hypothetical peer group
      conversations. In Study 1, children and early adolescents (N = 264) rated the
      attentiveness, criticalness, and admiration expressed in three conversations, in
      which the subject or a peer was mentioned in either an admiring, critical, or
      nonevaluative manner. In Study 2, a similar procedure was used with middle and
      late adolescents, as well as children and early adolescents (N = 187); two memory
      tasks were also administered to visit the issue of distortion in social
      cognition. In Study 3, a new sample (N = 1,019) representing the four age groups
      from Study 2 was presented with an ambiguous conversation and then asked to
      interpret who was the target (object of focus) and how that target was regarded.
      The findings from the three studies do not support the notion that adolescents
      believe others are attentive to and critical of their every move, or that their
      social cognition and perception is egocentric and distorted. Conceptual and
      methodological contributions are discussed, along with directions for additional
      research.

PMID- 11572313
TI  - A review of teen-tot programs: comprehensive clinical care for young parents and
      their children.
AB  - Comprehensive clinical programs for teenage mothers and their children, also
      known as teen-tot programs, have been a promising intervention to improve
      outcomes of teenage childbearing and parenting. However, much remains unknown
      regarding the efficacy of such programs. We reviewed four published evaluations
      of programs that provided medical care, counseling, contraception, guidance for
      parenting, and assistance with staying in school. The evaluations reported
      moderate success in preventing repeat pregnancies, helping teen mothers continue
      their education, and improving teen and infant health over 6 to 18 months.
      However, the evaluations had limitations that may have reduced or accentuated
      observed effectiveness. Teen-tot programs will continue to face the challenges of
      sustaining adequate long-term interventions and evaluations, and reducing the
      high attrition rate among program participants. It is concluded that increased
      support and funding for teen-tot programs and more complete evaluations are
      warranted.

PMID- 11572314
TI  - Employment during adolescence is associated with depression, inferior
      relationships, lower grades, and smoking.
AB  - A self-report questionnaire was administered to high school seniors to collect
      data on the psychological, behavioral, and social aspects of their lives. It was
      found that employment was associated with (1) greater depression; (2) inferior
      relationships with parents and best friend, including less time and physical
      contact with parents; (3) lower grade point average; and (4) smoking.

PMID- 11572315
TI  - Growth hormone: new ideas, recurring themes.

PMID- 11572316
TI  - Site-specific control of rat preadipocyte adipose conversion by ovarian status:
      Possible involvement of CCAAT/enhancer-binding protein transcription factors.
AB  - The preadipocyte-adipocyte conversion process from two intraabdominal
      (parametrial and perirenal fat depots) is differently affected by ovarian status
      in the rat. We have tested the hypothesis that these site-specific alterations of
      adipogenesis might be related to changes in the expression of the transcription
      factors c-mycand CCAAT/enhancer binding proteins (C/EBPalpha, -beta, and -zeta)
      that regulate proliferation and differentiation. The increased proliferation
      rates observed in parametrial and perirenal preadipocytes after ovariectomy were
      not linked to variations in c-myc mRNA levels. Expression of the early marker of
      adipogenesis, lipoprotein lipase (LPL), remained insensitive to the ovarian
      status in early differentiated parametrial and perirenal preadipocytes. By
      contrast, LPL expression increased in early differentiated sc preadipocytes from
      ovariectomized rats, an effect that was completely reversed by in vivo estradiol
      and progesterone treatment. Expression of C/EBPbeta protein was unaffected by
      ovarian status whatever the anatomic origin of the preadipocytes. By contrast,
      the levels of p42 and p30 isoforms of C/EBPalpha were specifically decreased in
      parametrial preadipocytes, an alteration that was completely corrected by in vivo
      administration of estradiol and progesterone. C/EBPzeta, a dominant inhibitor of
      C/EBPalpha and -beta, exhibited a strong site-specific expression since C/
      EBPzeta content was fivefold higher in sc preadipocytes than in deep
      intraabdominal cells whatever the ovarian status. Furthermore, ovariectomy
      selectively decreased C/EBPzeta levels in sc cells. In conclusion, our study
      suggests that some of the site-specific effects of ovariectomy on adipogenesis
      could involve, at least in part, altered expressions of C/EBPalpha and -zeta,
      both of which are important transcriptional regulators of fat cell
      differentiation and metabolism.

PMID- 11572317
TI  - Analysis of glucocorticoid and androgen receptor gene fusions delineates domains
      required for transcriptional specificity.
AB  - Androgen receptor (AR) and glucocorticoid receptor (GR) influence distinct
      physiologic responses in steroid-responsive cells despite their shared ability to
      selectively bind in vitro to the same canonical DNA sequence (TGTTCT). While the
      DNA-binding domains (DBDs) of these receptors are highly conserved, the amino N
      terminal domain (NTD) and hormone-binding domain (HBD) are evolutionarily
      divergent. To determine the relative contribution of these functional domains to
      steroid-specific effects in vivo, we constructed a panel of AR/GR gene fusions by
      interchanging the NTD, DBD, and HBD regions of each receptor and measured
      transcriptional regulatory activities in transfected kidney and prostate cell
      lines. We found that GR was approximately 10-fold more active than AR when tested
      with the mouse mammary tumor virus promoter, and that this difference in activity
      was primarily owing to sequence divergence in the NTDs. We also tested
      transcriptional activation of the androgen-dependent rat probasin promoter, and
      in this case, AR was at least twofold more active than GR. Analysis of the
      chimeric receptors revealed that this difference mapped to the DBD region of the
      two receptors. Transcriptional repression functions of the wild-type and chimeric
      receptors were measured using an activator protein 1 (AP-1) transrepression assay
      and identified the GR HBD as a more potent transrepressor of AP-1 transcriptional
      activation than the AR HBD. Taken together, our analyses reveal that evolutionary
      sequence divergence between AR and GR functional domains results in unique
      promoter-specific activities within biologic systems in which both AR and GR are
      normally expressed.

PMID- 11572318
TI  - Peptides derived from pro-growth hormone-releasing hormone activate p38 mitogen
      activated protein kinase in GH3 pituitary cells.
AB  - Posttranslational processing of the pro-growth hormone-releasing hormone
      (proGHRH) peptide can result in the formation of at least two peptide products:
      GHRH and the C-terminal peptide, GHRH-related peptide (GHRH-RP). While cyclic
      adenosine monophosphate transduces many of the actions of GHRH, other pathways
      also have been implicated in its actions. The aims of this study were to examine
      and characterize the activation of mitogen-activated protein kinase (MAPK)
      pathways by GHRH, and GHRH-RP in pituitary-derived GH3 cells, as well as the
      activation of the transcription factors that serve as substrates for these
      kinases. GHRH rapidly increased p44/p42 MAPK activity in GH3 cells in a protein
      kinase A-dependent and a protein kinase C-independent manner and stimulated the
      activation of the transcription factor Elk-1. By contrast, GHRH-RP and p75-92NH2
      had no effect on p44/p42 MAPK phosphorylation in these cells. Additionally, we
      determined that all three peptides, GHRH, GHRH-RP, and p75-92NH2, rapidly and
      specifically increase phosphorylation of p38 MAPK and stimulate the activation of
      the nuclear factor CHOP. These are the first studies to demonstrate the
      activation of Elk-1 by GHRH and the activation of p38 MAPK and CHOP by GHRH, GHRH
      RP, and p75-92NH2. We conclude that members of the GHRH family of peptides
      differentially activate multiple intracellular signaling pathways and suggest
      that the biologic actions of GHRH may be far more diverse than previously
      thought.

PMID- 11572319
TI  - Progesterone together with estrogen attenuates homologous upregulation of
      gonadotropin-releasing hormone receptor mRNA in primary cultured rat pituitary
      cells.
AB  - In a previous study, we clearly demonstrated that an application of gonadotropin
      releasing hormone (GnRH) to cultured rat pituitary cells increased the expression
      of GnRH receptor (GnRH-R) mRNA through transcriptional activation of GnRH-R gene
      rather than suppression of the turnover rate of GnRH-R mRNA. Along with GnRH,
      gonadal steroids seem to be an important regulator for GnRH-R expression in the
      pituitary gland. Recent in vivo studies reported that an application of gonadal
      steroids to gonadectomized animals modulated GnRH-R mRNA expression in the
      pituitary gland. However, it has not been clearly understood whether steroids may
      act directly at the pituitary or indirectly via modulation of hypothalamic GnRH
      release. Therefore, we assessed the effects of estrogen and progesterone on GnRH
      R mRNA expression in primary cultured female rat pituitary cells. Neither
      estradiol nor progesterone modulates the basal expression of GnRH-R mRNA in
      primary cultured pituitary cells. When cultured pituitary cells were exposed to
      different doses of estradiol in combination with GnRH (0.2 nM), the GnRH
      stimulated increment of GnRH-R mRNA expression was not significantly changed by
      estradiol at any given doses. However, when different doses of progesterone were
      added to primary cultured pituitary cells in combination with GnRH (0.2 nM), GnRH
      induced increases in GnRH-R mRNA levels were reduced in a dose-related manner,
      showing a significant reduction at 100 nM progesterone. Furthermore, the addition
      of estradiol reinforced the suppressive effect of progesterone on the homologous
      upregulation of GnRH-R mRNA expression. Collectively, our results clearly
      demonstrated that progesterone directly attenuates the homologous upregulation of
      GnRH-R mRNA expression at the pituitary level, and that estradiol potentiates the
      effect of progesterone.

PMID- 11572320
TI  - Clinical testing results and high patient satisfaction with a new needle-free
      device for growth hormone in young children.
AB  - Fifty children ages 4-10 yr with type 1 diabetes mellitus volunteered to
      participate in a study to evaluate and compare a new needle-free device developed
      for growth hormone delivery. Children answered descriptive questions related to
      nervousness and worry, hurt or pain, redness or bleeding, and stinging and
      wetness. Choices for answers for each of these five questions were none, a
      little, or a lot. None or a little was also combined to give a minimal category.
      Children also answered four questions that compared the needle-free device to
      their morning insulin needle injection in reference to ease of use, pain,
      nervousness, and overall preference. Half the children had single comfort rings
      inserted to increase the injection pressure. Results indicated no difference in
      question responses with or without pressure rings. Pain (92%), erythema (96%),
      worry (90%), stinging (86%) and wetness (96%) were minimal and significant (0.001
      > p < 0.03) following all questions. Results of the comparative questionnaire
      indicated that the device was easier (p < 0.03) to use than needles and
      significantly preferred (p < 0.001) in 74% of children under age 10.

PMID- 11572323
TI  - Treatment with growth hormone in short children born with intrauterine growth
      retardation.
AB  - In the past 10 yr, the potential benefits of treatment with growth hormone (GH)
      in children born with intrauterine growth retardation (IUGR) have been well
      documented. In this study, 46 children with IUGR received 3 yr of GH treatment
      (0.2 IU/kg of body wt) followed by a further 3 yr of observation without
      treatment. Height velocity (HV) increased dramatically during the first year of
      treatment, and over the 3-yr treatment period there was a 2 standard deviation
      score (SDS) gain in height (from -3.3+/-0.7 SDS to -1.3+/-0.3 SDS). Bone age (BA)
      was increased by 4 yr during treatment. A dramatic decrease in HV was observed in
      the second phase of the study when patients were no longer receiving GH.
      Similarly, the gain in BA during the observation period was only half that
      observed during the treatment period. No clinically significant changes were
      observed in laboratory test results, and no clinical adverse events could be
      related to treatment. In conclusion, the data provide evidence of a beneficial
      effect of GH treatment in IUGR children. However, adequate treatment duration is
      critical, because growth velocity decreases dramatically on discontinuation of GH
      treatment.

PMID- 11572324
TI  - Long-term therapy with recombinant human growth hormone (Saizen) in children with
      idiopathic and organic growth hormone deficiency.
AB  - In an open-label study, 69 children with organic or idiopathic growth hormone
      deficiency (GHD) were treated with recombinant human growth hormone (Saizen) for
      an average of 64.4 mo, with treatment periods as long as 140.9 mo. Auxologic
      measurements, including height velocity, height standard deviation score, and
      bone age, were made on a regular basis. The data suggest that long-term treatment
      with Saizen in children with GHD results in a positive catch-up growth response
      and proportionate changes in bone age vs height age during treatment. In
      addition, long-term Saizen therapy was well tolerated, with the majority of
      adverse events related to common childhood disorders or existing baseline medical
      conditions and not to study treatment. There were no significant changes in
      laboratory safety data or vital signs, and no positive antibody tests for Saizen.

PMID- 11572321
TI  - Pulling strings below the surface: hormone receptor signaling through inhibition
      of protein tyrosine phosphatases.
AB  - Hormones, cytokines, and related proteins (such as soluble hormone receptors)
      play an important role as therapeutic agents. Most hormone receptors signal
      through a mechanism that involves phosphorylation of the receptor's tyrosine
      residues. At any given moment, the receptor's phosphorylation state depends on
      the balance of kinase and phosphatase activities. Recent findings point to the
      exciting possibility that receptor signaling can be regulated by inhibition of
      protein tyrosine phosphatases (PTPs) that specifically hydrolyze receptor
      tyrosine-phosphates, or their immediate downstream effectors. This strategy has
      now been firmly validated for the insulin receptor and PTP1B; inhibiting PTP1B
      activity results in stimulation of the insulin receptor and signaling, even in
      the absence of insulin. This and similar findings suggest that PTP inhibitors
      have potential as hormone mimetics. In the present review, we outline this new
      paradigm for therapeutic regulation of the insulin receptor and discuss evidence
      that hints at other specific receptor-PTP pairs.

PMID- 11572322
TI  - Growth hormone-releasing hormone combined with arginine or growth hormone
      secretagogues for the diagnosis of growth hormone deficiency in adults.
AB  - Insulin-induced hypoglycemia (ITT) is currently the "gold-standard" test for the
      diagnosis of adult growth hormone deficiency (GHD). ITT is often contraindicated,
      however, particularly in conditions that are also common in patients with
      suspected GHD. Used alone, GH-releasing hormone (GHRH) has no diagnostic value
      owing to within-subject variability and the inability to distinguish GHD from
      normal subjects. When combined with arginine, however, GHRH becomes a potent and
      reproducible test, which is unaffected by gender and aging, showing excellent
      specificity. The GHRH+ arginine (ARG) test distinguishes GHD patients from normal
      subjects and is at least as sensitive as ITT, provided that appropriate cutoff
      limits are considered. Its reliability for retesting GHD has also been
      demonstrated. The GHRH+ARG test can also be performed in a shorter procedure,
      resulting in potential for cost reduction. Synthetic GH secretagogues (GHSs)
      possess a strong and reproducible GH-releasing effect and synergize with GHRH.
      The combination of GHRH and a peptidyl GHS, such as hexarelin or GH-releasing
      peptide-6, has recently been shown as another reliable test for the diagnosis of
      adult GHD, again provided that the cutoff limit is appropriate to the potency of
      the test. Thus, GHRH combined with either arginine or GHS is a potential tool for
      the diagnosis of adult GHD.

PMID- 11572325
TI  - Long-term results of growth hormone therapy in Turner syndrome.
AB  - Short stature is one of the main features of Turner syndrome. Today, most
      patients are treated with growth hormone (GH) to improve adult height. We have
      reviewed the literature reporting adult height in patients with Turner syndrome
      treated with GH alone or in combination with oxandrolone. The reported adult
      heights as well as the height gain over projected or predicted height are still
      preliminary and vary considerably among studies. There is some evidence that the
      age of onset of therapy, dose of GH, duration of GH therapy, target height, time
      of estrogen substitution, or concurrent treatment with oxandrolone affect adult
      height. The reported height gains over projected height range from -0.20 to +16.0
      cm (median: 5.1 cm) in patients treated with GH and from +0.68 cm to +10.3
      (median: 6.40 cm) in patients treated with GH and oxandrolone. Thus, the
      presently available data are extremely varied and need further detailed analysis
      after all ongoing clinical trials have published the final results of all
      patients included in the study.

PMID- 11572326
TI  - Outcome of growth hormone therapy in children with growth hormone deficiency
      showing an inadequate response to growth hormone-releasing hormone.
AB  - Saizen (recombinant growth hormone [GH]), 0.2 mg/(kg x wk), was given in an open
      label fashion for an average of 51 mo to 27 children with presumed idiopathic GH
      deficiency who had withdrawn from a trial of Geref (recombinant GH-releasing
      hormone [GHRH] 1-29) because of inadequate height velocity (HV) (25 children),
      the onset of puberty (1 child), or injection site reactions (1 child).
      Measurements were made every 3-12 mo of a number of auxologic variables,
      including HV, height standard deviation score, and bone age. The children in the
      study showed excellent responses to Saizen. Moreover, first-year growth during
      Saizen therapy was inversely correlated with the GH response to provocative GHRH
      testing carried out 6 and 12 mo after the initiation of Geref treatment. These
      findings indicate that GH is effective in accelerating growth in GH-deficient
      children who do not show or maintain a satisfactory response to treatment with
      GHRH. In addition, they suggest that the initial response to GH therapy used in
      this way can be predicted by means of provoc-ative testing.

PMID- 11572327
TI  - Case of adrenocorticotropic hormone-independent macronodular adrenal hyperplasia
      with possible adrenal hypersensitivity to angiotensin II.
AB  - With increasing case reports, it has been indicated that some cases with
      adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia
      (AIMAH) show abnormal responses in cortisol to various stimulation tests. Here we
      report a case of AIMAH that showed an aberrant response to angiotensin II via AT1
      receptor in cortisol hypersecretion. A 53-yr-old man was admitted to our division
      seeking further examinations for the possible diagnosis of Cushing's syndrome. He
      had hypertension, diabetes mellitus, and physical stigmata, such as moon face and
      central obesity. His plasma ACTH level was undetectable, and plasma cortisol
      level was high. Plasma cortisol showed no normal diurnal rhythm and was not
      suppressed after the administration of 8 mg of dexamethasone. Abdominal computed
      tomography demonstrated nodular enlargement of bilateral adrenal glands. He was
      diagnosed with Cushing's syndrome owing to AIMAH. An injection of arginine
      vasopressin (AVP) increased plasma cortisol and aldosterone levels, whereas ACTH
      remained undetectable. After 4 h in an upright position, plasma cortisol and
      aldosterone levels were increased. Pretreatment with candesartan, angiotensin II
      receptor AT1 antagonist, blocked the increase in plasma cortisol level. These
      results suggested a possibility of adrenal hypersensitivity to angiotensin II and
      AVP in cortisol secretion. Bilateral laparoscopic adrenalectomy was performed.
      The histological findings of the specimen were compatible with AIMAH. In summary,
      we have made the first report on a case of AIMAH with possible hypersensitivity
      to angiotensin II.

PMID- 11572329
TI  - Pancreatic beta-cells from obese-hyperglycemic mice are characterized by
      excessive firing of cytoplasmic Ca2+ transients.
AB  - Pancreatic beta-cells from obese-hyperglycemic (ob/ob) mice are widely used for
      studying the mechanisms of insulin release, including its regulation by the
      cytoplasmic Ca2+ concentration ([Ca2+]i). In this study, we compared changes of
      [Ca2+]i in single beta-cells isolated from ob/ob mice with those from lean mice
      using dual-wavelength microfluorometry and the indicator fura-2. There were no
      differences in the frequency, amplitude, and half-width of the slow oscillations
      induced by glucose. Most beta-cells from the obese mice responded to 10 mM
      caffeine with transformation of the oscillations into sustained elevation of
      [Ca2+]i, a process counteracted by ryanodine. The beta-cells from the obese mice
      were characterized by ample generation of [Ca2+]i transients, which increased in
      number in the presence of glucagon. The transients became less frequent when
      leptin was added at a concentration as low as 1 nM. It is suggested that the
      excessive firing of [Ca2+]i transients in the ob/ob mice is owing to the absence
      of leptin and is mediated by activation of the phospholipase C signaling pathway.

PMID- 11572328
TI  - Nongenomic action of steroids in myometrial contractility.
AB  - Steroid hormones are involved in several fundamental aspects of all living
      beings, with a few slight chemical differences among steroids being enough to
      give them the extraordinarily diverse biologic specificities that are important
      in animal physiology and medical therapeutics. Indeed, in the uterus, they have a
      remarkable action on uterine contractility with physiologic significance in the
      important reproductive processes of mammalian pregnancy and parturition. The
      regulation of progesterone on the myometrial contractile activity and related
      wider subjects of the endocrinology of pregnancy and parturition have been
      reviewed many times during the twentieth century. However, new data indicate that
      several progesterone metabolites and some synthetic steroids induce a
      progesterone-like uterine-relaxing effect. Experimental evidence from our
      laboratory has shown that 5-reduced progestins and androgens are more potent than
      progesterone itself in decreasing uterine contractility. The purpose of this
      review is to update current knowledge of endogenous and exogenous steroids on the
      phenomenon of uterine contractility, by summarizing their structural differences
      to induce changes on this process and discussing the possible mechanism of
      steroids to regulate uterine muscle activity.

PMID- 11572330
TI  - Cold-induced increment in rat adrenal gland type II deiodinase is corticosterone
      dependent.
AB  - In this study we analyzed whether corticosterone synthesis is involved in the
      regulation of adrenal gland type II deiodinase (AG-D2) activity during acute cold
      exposure. Two well-known inhibitors of steroidogenesis, aminoglutethimide (AGT)
      and metyrapone (MTP), were administered to male Wistar rats maintained either at
      room temperature or acutely exposed to cold (1 h at 4 degrees C). AG-D2 activity
      was measured by the radioiodide release method, and corticosterone circulating
      levels were measured by competitive protein binding assay. Results show that
      resting corticosterone levels and AG-D2 activity were lower in both AGT- and MTP
      treated rats. Furthermore, the phasic increase normally exhibited by AG-D2
      activity in response to acute cold stress was blunted in AGT- and MTP-treated
      animals. Therefore, we conclude that corticosterone synthesis is necessary in
      preserving the physiologic response of AG-D2 activity to cold exposure.

PMID- 11572331
TI  - Stathmin levels in growth plate chondrocytes are modulated by vitamin D3
      metabolites and transforming growth factor-beta1 and are associated with
      proliferation.
AB  - Stathmin is a highly conserved, phosphorylated cytosolic protein that is found at
      decreased levels in all cells as they become more terminally differentiated, or
      when they decrease in their rate of proliferation. This study examined the
      hypothesis that stathmin levels in growth plate chondrocytes decreases as
      endochondral maturation increases. To test this hypothesis, we used a
      costochondral growth plate chondrocyte cell culture model. Cells derived from the
      resting zone (RC) express twice as much stathmin mRNA in culture and have twice
      as much stathmin protein as cells derived from the post proliferative growth zone
      ([GC]; prehypertrophic and upper hypertrophic cell zones). Stathmin levels in
      vivo were assessed by immunohistochemistry. To assess the effects of agents that
      modulate proliferation and differentiation, RC and GC chondrocytes were cultured
      in the presence of 10(-10) to 10(-8) M 1alpha,25-(OH)2D3, which regulates
      proliferation in both cell types but affects differentiation of only GC cells, or
      10(-9) to 10(-7) M 24R,25-(OH)2D3, which regulates differentiation and maturation
      of RC cells but decreases proliferation of GC cells. In addition, RC cells were
      treated with 0.44 or 0.88 ng/mL of recombinant human transforming growth factor
      beta1 (rhTGF-beta1), which stimulates proliferation of RC cells and regulates
      proteoglycan production, but not alkaline phosphatase activity. Stathmin protein
      levels were determined using quantitative immunoblots, with recombinant human
      stathmin as a standard. The results show that stathmin levels are associated with
      proliferation. Proliferating chondrocytes in vivo exhibited higher levels of
      immunoreactive stathmin than either RC or GC cells in the growth plate. In
      culture, 1alpha,25-(OH)2D3 caused a dose-dependent decrease in stathmin in RC and
      GC cells within 24 h. 24R, 25-(OH)2D3 also reduced stathmin levels in GC cells
      within 24 h but only affected RC cells after prolonged exposures (96 h), at which
      time RC cells express a GC-like phenotype. rhTGF-beta1 caused an increase in
      stathmin levels in RC cells. Stathmin levels are sensitive to protein kinase C
      (PKC) in other cells. Inhibition of PKC with chelerythrine had no effect on the
      response of RC cells to 1alpha,25-(OH)2D3 but it blocked the effect of rhTGF
      beta1, indicating that decreases in stathmin by vitamin D3 metabolites may not be
      modulated by PKC, whereas increases in stathmin via rhTGF-beta1 may be regulated
      via a PKC-dependent mechanism. These results support the hypothesis that
      constitutively expressed levels of stathmin are related to cell maturation state
      and that they are modulated by factors that regulate proliferation.

PMID- 11572333
TI  - The effects of pressure loading on the dynamics of a curved piezostructure.

PMID- 11572332
TI  - On the effect of boundaries on radiation resistance of plates.

PMID- 11572334
TI  - Comment on "Reducing seat dip attenuation" [J. Acoust. Soc. Am. 108, 2211-2218
      (2000)].

PMID- 11572335
TI  - Improving object classification with biomimetic sonar.

PMID- 11572336
TI  - Masked threshold difference due to masker harmonicity: uniform modulation rates
      of auditory filter outputs versus periodicity in waveform fine structure.

PMID- 11572337
TI  - On scattering from a bubble located near a flat air-water interface: laboratory
      measurements and modeling.
AB  - Scattering by a single bubble near a flat air-water interface is investigated
      theoretically and experimentally. A ray-acoustic interpretation is used to
      describe the four scattering paths, from source to bubble to receiver, that
      determine the response of the bubble. Multiple scattering effects are accounted
      for using a closed-form solution derived from the multiple scattering series.
      Experiments are performed by placing a bubble with radius a approximately 425
      microm on a fine nylon thread, which is approximately 100 microm in diameter and
      practically transparent to sound, at a distance d from the interface. The primary
      variable is d and it ranges from 1 a to 100 a. The bubble is excited by tone
      bursts with a center frequency of 120 kHz, with the transducers arranged in both
      bistatic and monostatic configurations. Theory and experiment are in good
      agreement, verifying the dominant effect of the four paths in the response of the
      bubble, with multiple scattering playing a role for kd < 1, where k is the wave
      number of the medium. In the long-range limit our simulations agree with those of
      Ye and Feuillade [J. Acoust. Soc. Am. 102, 798-805 (1997)] including the shifting
      of the bubble's resonant frequency. The dependence of scattering on transducer
      arrangement, range to bubble, grazing angle, and phase relation among the four
      paths, vis-a-vis monostatic and bistatic scattering, is discussed.

PMID- 11572338
TI  - Crack characterization using guided circumferential waves.
AB  - This paper examines the propagation of guided circumferential waves in a hollow
      isotropic cylinder that contains a crack, with the goal of using these guided
      waves to both locate and size the crack. The crack is sized using a modified
      Auld's formula, which relates the crack's length to a reflected energy
      coefficient. The crack is then located by operating on the backscattered signal
      with a time-frequency digital signal processing (DSP) technique, and then
      comparing these results to those obtained if the cylinder is perfect. The guided
      circumferential waves are generated with a commercial finite element method (FEM)
      code. One objective of this work is to demonstrate the effectiveness of using
      sophisticated DSP techniques to describe the effect of scattering on dispersive
      waves, showing it is possible to characterize cracks systematically and
      accurately by quantifying this scattering effect. The results show that the need
      for high frequency signals to detect small cracks is significantly decreased by
      using these techniques.

PMID- 11572339
TI  - Coherent backscattering of elastic waves: specific role of source, polarization,
      and near field.
AB  - Calculation of coherent backscattering of elastic waves in an infinite isotropic
      random medium is presented. Despite the simplicity of this geometry, this
      calculation highlights several specific aspects for seismic detection: near field
      detection, polarization, and the symmetry of the source. Line profiles and
      enhancement factors are seen to be time independent and are calculated for
      kinetic, shear, and compressional energy.

PMID- 11572340
TI  - On the character of acoustic waves at the interface between hard and soft solids
      and liquids.
AB  - Laser ultrasonics is used to optically excite and detect acoustic waves at the
      interface between a liquid and a solid or coated solid. Several case studies show
      that this technique is feasible to investigate experimentally the theoretically
      predicted fundamental properties of different aspects of interface waves at
      liquid-solid interfaces and to characterize the elastic properties of soft
      solids. The theoretical prediction that the leaky Rayleigh (LR)-type root of the
      characteristic determinant becomes forbidden when the shear velocity of the solid
      lies below the bulk velocity of the liquid was experimentally confirmed. The
      depth profiling and nondestructive testing potential of Scholte waves was
      experimentally illustrated and explained by the properties of the wave
      displacement profile.

PMID- 11572341
TI  - Determination of Lamb mode eigenvalues.
AB  - An original method is presented to determine the complex Lamb wave spectrum by
      using a numerical spectral method applied to the elasticity equations. This
      method presents the advantage to directly determine complex wave numbers for a
      given frequency via a classical matricial eigenvalue problem, and allows the wave
      numbers to be determined at relatively high frequencies (i.e., corresponding to
      many propagating modes). It does not need initial guess values for the wave
      numbers, contrary to the usual method of root finding of the Rayleigh-Lamb
      frequency equations (dispersion relation) in the complex plane. Results are
      presented and the method is discussed.

PMID- 11572342
TI  - Theory and experiments on the coupling of two Helmholtz resonators.
AB  - The acoustic coupling between closely located acoustic resonators can have a
      significant effect on the resonance properties. Examples of the influence of
      coupling include pipe musical instruments such as flue organs or flutes, where
      the coupling may affect the sound. Here, a physical model of a system of two
      coupled Helmholtz resonators is developed. The coupling is described by the
      mutual impedance between the neck openings, and an additive reflection impedance
      modification to the radiation impedance, which models the effect of reflections
      from the outer "shell" of the other resonator. The theoretical predictions show a
      good agreement with measurements also reported here. Finally, the effects of
      coupling on the present system are analyzed.

PMID- 11572343
TI  - Sound propagation in rigid bends: a multimodal approach.
AB  - The sound propagation in a waveguide with bend of finite constant curvature is
      analyzed using multimodal decomposition. Two infinite first-order differential
      equations are constructed for the pressure and velocity in the bend, projected on
      the local transverse modes. A Riccati equation for the impedance matrix is then
      derived, which can be numerically integrated after truncation at a sufficient
      number of modes. An example of validation is considered and results show the
      accuracy of the method and its suitability for the formulation of radiation
      conditions. Reflection and transmission coefficients are also computed, showing
      the importance of higher order mode generation at the junction between the bend
      and the straight ducts. The case of varying cross-section curved ducts is also
      considered using multimodal decomposition.

PMID- 11572344
TI  - Tomographic inversion of geoacoustic properties in a range-dependent shallow
      water environment.
AB  - This paper presents a matched-field tomographic method to estimate the
      geoacoustic properties of the ocean bottom for a range-dependent medium in
      shallow water. The inversion method has been developed in order to interpret
      experimental data from the Haro Strait PRIMER sea trial. This experiment was
      carried out in June '96 and used low-frequency broadband signals that were
      received on three vertical line arrays. Inversion of the data is particularly
      difficult because of the complex bathymetry of the Haro Strait experimental site.
      For this inversion, a range-dependent ray code was developed to solve the forward
      problem, allowing an arbitrarily layered bottom environment. The inversion scheme
      is based on modeling the propagation time and the amplitude of the recorded data,
      and a simple new cost function is proposed. The signal ray paths are identified
      automatically using a simple process that compares calculated and measured travel
      times. Data from multiple source positions are used to invert the range
      dependence of the geoacoustic model. The environment is separated into segments,
      and within each segment the inversion is carried out layer by layer for a
      multilayer geoacoustic model. Starting with the topmost layer, the range
      dependent thickness and sound speed are estimated via a Monte Carlo method.
      Inversion results are presented for synthetic and experimental data from the Haro
      Strait sea trial.

PMID- 11572345
TI  - Thin coating characterization by Rayleigh waves: an analytical model based on
      normal-mode theory.
AB  - The acousto-optic technique to evaluate coated substrates, presented by Devolder
      et al. [Appl. Phys. Lett. 68, 1732 (1996)], uses the phase dependence of the
      reflected beam on the coating parameters. In this theoretical paper, a fully
      analytical model, based on normal-mode theory, is applied to this problem. It
      gives a transparent expression for the phase shift between the reflected and the
      incident field due to the presence of thin coatings (coating thickness much
      smaller than wavelength sound). The known numerical results from Fourier
      simulations, i.e. the phase dependency on the coating parameters and the
      advantages of using higher frequencies and wider beams, are reproduced. However,
      thanks to the analytical nature of the new theory, additional results are
      obtained. The calculation time is reduced by two orders of magnitude, which is
      important for the inverse problem. A technique for absolute thickness
      measurements is proposed. Measuring more to the right of the second reflected
      maximum increases the phase sensitivity. The versatility of the normal-mode
      approach is illustrated by applying it to other nondestructive testing (NDT)
      applications, such as hardness determination and adhesion testing, which are
      briefly discussed.

PMID- 11572346
TI  - Vibratory characteristics of multistep nonuniform orthotropic shear plates with
      line spring supports and line masses.
AB  - A new exact approach for free-vibration analysis of multistep nonuniform
      orthotropic shear plates with line spring supports and line masses is presented.
      The governing differential equation for free vibrations of an orthotropic shear
      plate with variably distributed mass and stiffness is established. It is proved
      that it is possible to separate a shear plate as two independent shear beams for
      free-vibration analysis. The jkth natural frequency of a shear plate is equal to
      the square root of the square sum of the jth natural frequency of a shear beam
      and the kth natural frequency of another shear beam. The jkth mode shape of the
      shear plate is the product of the jth mode shape of a shear beam and the kth mode
      shape of another shear beam. In this paper, the function for describing the
      distribution of mass of each step plate can be selected as an arbitrary one, and
      the distribution of shear stiffness is expressed as a functional relation with
      the mass distribution, and vice versa. The exact solutions of one-step shear
      plates with varying cross section are obtained first for eight cases. Then, the
      derived exact solutions are used to establish the frequency equation of a
      multistep nonuniform orthotropic shear plate with spring supports and line masses
      using the transfer matrix method and the recurrence method developed in this
      paper. The numerical example shows that the calculated results are in good
      agreement with the experimental data, and the proposed procedure is an exact and
      efficient method.

PMID- 11572347
TI  - Mode isolation: a new algorithm for modal parameter identification.
AB  - Multiple degree of freedom (MDOF) algorithms are the dominant methods for
      extracting modal parameters from measured data. These methods are founded on the
      notion that because the response of a linear dynamic system is the sum of many
      modal contributions, the extraction technique must deal with all of the modal
      parameters in a simultaneous fashion. The Mode Isolation Algorithm (MIA)
      described here is a frequency domain formulation that takes an alternative
      viewpoint. It extracts the modal parameters of each mode in an iterative search,
      and then refines the estimation of each mode by isolating its effect from the
      other modal contributions. The first iteration estimates modes in a hierarchy of
      their dominance. As each mode is estimated, its contribution is subtracted from
      the data set, until all that remains is noise. The second and subsequent
      iterations subtract the current estimates for all other modes to identify the
      properties of the mode under consideration. The various operations are described
      in detail, and then illustrated using data from a four-degree-of-freedom system
      that was previously used to assess the Eigensystem Realization Algorithm (ERA)
      and Enhanced ERA. Eigenvalues and mode shapes are compared for each algorithm.
      Another example analyzes simulated data for a cantilever beam with three
      suspended one-degree-of-freedom subsystems, in which the parameters are adjusted
      to bring two natural frequencies into close proximity. The results suggest that
      MIA is more accurate, and more robust in the treatment of noisy data, than either
      ERA version, and that it is able to identify modes whose bandwidth is comparable
      to the difference of adjacent natural frequencies.

PMID- 11572348
TI  - An efficient formulation of Krylov's prediction model for train induced
      vibrations based on the dynamic reciprocity theorem.
AB  - In Krylov's analytical prediction model, the free field vibration response during
      the passage of a train is written as the superposition of the effect of all
      sleeper forces, using Lamb's approximate solution for the Green's function of a
      halfspace. When this formulation is extended with the Green's functions of a
      layered soil, considerable computational effort is required if these Green's
      functions are needed in a wide range of source-receiver distances and
      frequencies. It is demonstrated in this paper how the free field response can
      alternatively be computed, using the dynamic reciprocity theorem, applied to
      moving loads. The formulation is based on the response of the soil due to the
      moving load distribution for a single axle load. The equations are written in the
      wave-number-frequency domain, accounting for the invariance of the geometry in
      the direction of the track. The approach allows for a very efficient calculation
      of the free field vibration response, distinguishing the quasistatic contribution
      from the effect of the sleeper passage frequency and its higher harmonics. The
      methodology is validated by means of in situ vibration measurements during the
      passage of a Thalys high-speed train on the track between Brussels and Paris. It
      is shown that the model has good predictive capabilities in the near field at low
      and high frequencies, but underestimates the response in the midfrequency band.

PMID- 11572349
TI  - Experimental study of structure-borne sound transmission loss of mechanical
      joints.
AB  - A mechanical joint is one of the most effective ways to reduce the transmission
      of structure-borne sound. In order to increase the transmission loss, heavily
      damped joints are often used, which, in many cases, will reduce the structure
      integrity and hence can only be used in limited cases. In this study attention is
      focused on a type of resonant joint, i.e., a joint which will increase the
      transmission loss but will not reduce the structure integrity. The study is based
      on experiments in a one-dimensional structure. It is found that by adjusting the
      overlap of the joint, the transmission loss of 30 dB can be obtained at a certain
      frequency range without adding any dissipative materials. The mechanism of this
      high transmission loss is the cantilever-type resonance. The resonant frequency
      can be predicted precisely. The influence of extra dissipative material is
      investigated. The performance of the same joint in a finite structure is also
      examined by using the concept of vibrational insertion loss. When there is a
      certain damping in a finite system, a rather high insertion loss can still be
      achieved by using the above-mentioned joint, but the resonant frequency is
      shifted to higher end. It seems that the effective length of the cantilever is
      shortened by the finiteness.

PMID- 11572350
TI  - Acoustic waves generated by pulsed microwaves in viscoelastic rods: modeling and
      experimental verification.
AB  - The acoustic wave generation in a specimen irradiated by a pulsed microwave is
      predicted theoretically. The specimen is a viscoelastic rod inserted into a wave
      guide. The model is based on Maxwell's equations, heat equation and
      thermoviscoelasticity theory. Computations show the presence of temperature
      oscillations due to the electromagnetic interferences in the irradiated rod if
      its electromagnetic absorption is low. An experimental method to infer indirectly
      the detailed behavior of microwave-generated acoustic waves in polymer rods,
      including the influence of electromagnetic wave reflection at the rod ends, is
      presented. The method consists of measuring the oscillations in the particle
      acceleration detected at the end of the rod that are induced by variations in the
      polymer rod length. The oscillations are caused by changing electromagnetic
      standing-wave conditions within the rod. It is found that these oscillations are
      in agreement in period, amplitude, and phase, with independent values of the
      complex dielectric constant and complex acoustic slowness of the polyvinyl
      chloride samples used in the study.

PMID- 11572351
TI  - Modifying modal characteristics of sound fields by state feedback control.
AB  - State feedback control of a sound field is investigated for improving the
      irregular distribution of the natural frequencies at low frequencies. A state
      space description of a sound field is derived from an inhomogeneous wave equation
      using the finite element method. The feedback control system is realized as a
      feedback filter between sensor microphones and control sources using a state
      estimator for a linear dynamic system. Pole allocation is employed for
      calculating the state feedback gain vector, such that the roots of the closed
      loop system have the desired modal distribution. Computer simulations are
      performed to demonstrate the control achieved by distributing the lowest undamped
      natural frequencies in a uniform manner. As a result, the transfer functions with
      the state feedback control are modified so as to have peaks at identical
      intervals for the frequency range of interest. A control experiment in an
      enclosure is carried out with the same objective of control as modeled in the
      simulations. The experiment verifies that the desired modal distribution can be
      achieved by introducing the proposed state feedback control into a sound field.

PMID- 11572352
TI  - Evaluation of decay times in coupled spaces: Bayesian parameter estimation.
AB  - Determination of sound decay times in coupled spaces often demands considerable
      effort. Based on Schroeder's backward integration of room impulse responses, it
      is often difficult to distinguish different portions of multirate sound energy
      decay functions. A model-based parameter estimation method, using Bayesian
      probabilistic inference, proves to be a powerful tool for evaluating decay times.
      A decay model due to one of the authors [N. Xiang, J. Acoust. Soc. Am. 98, 2112
      2121 (1995)] is extended to multirate decay functions. Following a summary of
      Bayesian model-based parameter estimation, the present paper discusses estimates
      in terms of both synthesized and measured decay functions. No careful estimation
      of initial values is required, in contrast to gradient-based approaches. The
      resulting robust algorithmic estimation of more than one decay time, from
      experimentally measured decay functions, is clearly superior to the existing
      nonlinear regression approach.

PMID- 11572353
TI  - Linear prediction coding analysis and self-organizing feature map as tools to
      classify stress calls of domestic pigs (Sus scrofa).
AB  - It is assumed that calls may give information about the inner (emotional) state
      of an animal. Hence, in the last years sound analysis has become an increasingly
      important tool for the interpretation of the behavior, the health condition, and
      the well-being of animals. A procedure was developed that allows the
      characterization, classification, and visualization of the cluster structures of
      stress calls of domestic pigs (Sus scrofa). Based on the acoustic model of the
      sound production the extraction of features from calls was performed with linear
      prediction coding (LPC). A vector-based self-organizing neuronal network was
      trained with the determined LPC coefficients, resulting in a feature map. The
      cluster structure of the calls was then visualized with a unified matrix and the
      neurons were labeled for their input origin. The basic applicability of the
      procedure was tested by using two examples which were of special interest for a
      possible evaluation of the normal farming practice. The procedure worked well
      both in discriminating individual piglets by their scream characteristics and in
      classifying pig stress calls vs other calls and noise occurring under normal
      farming conditions.

PMID- 11572354
TI  - Middle-ear function with tympanic-membrane perforations. I. Measurements and
      mechanisms.
AB  - Sound transmission through ears with tympanic-membrane (TM) perforations is not
      well understood. Here, measurements on human-cadaver ears are reported that
      describe sound transmission through the middle ear with experimentally produced
      perforations, which range from 0.5 to 5.0 mm in diameter. Three response
      variables were measured with acoustic stimulation at the TM: stapes velocity,
      middle-ear cavity sound pressure, and acoustic impedance at the TM. The stapes
      velocity measurements show that perforations cause frequency-dependent losses; at
      low frequencies losses are largest and increase as perforation size increases.
      Measurements of middle-ear cavity pressure coupled with the stapes-velocity
      measurements indicate that the dominant mechanism for loss with TM perforations
      is reduction in pressure difference across the TM; changes in TM-to-ossicular
      coupling generally contribute less than 5 dB to the loss. Measurements of middle
      ear input impedance indicate that for low frequencies, the input impedance with a
      perforation approximates the impedance of the middle-ear cavity; as the
      perforation size increases, the similarity to the cavity's impedance extends to
      higher frequencies. The collection of results suggests that the effects of
      perforations can be represented by the path for air-volume flow from the ear
      canal to the middle-ear cavity. The quantitative description of perforation
      induced losses may help clinicians determine, in an ear with a perforation,
      whether poor hearing results only from the perforation or whether other pathology
      should be expected.

PMID- 11572355
TI  - Middle-ear function with tympanic-membrane perforations. II. A simple model.
AB  - A quantitative model of the human middle ear with a tympanic-membrane (TM)
      perforation is developed. The model is constrained by several types of acoustic
      measurements made on human cadaver ears, which indicate that perforation-induced
      changes in transmission result primarily from changes in driving pressure across
      the TM and that perforation-induced change in the structure of the TM and its
      coupling to the ossicles contributes a substantially smaller component. The model
      represents the effect of a perforation on the pressure difference across the TM
      by inclusion of a path for sound coupling through the perforation from the ear
      canal to the middle-ear cavity. The model implies that hearing loss with
      perforations depends primarily on three quantities: the perforation diameter,
      sound frequency, and the volume of air in the middle-ear cavity. For the
      conditions that produce the largest hearing loss (low frequency and large
      perforation), the model yields a simple dependence of loss on frequency,
      perforation diameter, and middle-ear cavity volume. Predictions from this model
      may be useful to clinicians in determining whether, in particular cases, hearing
      losses are explainable by the observed perforations or if additional pathology
      must be involved.

PMID- 11572356
TI  - Wideband reflectance tympanometry in chinchillas and human.
AB  - Wideband reflectance tympanometry was performed on twelve chinchillas ears. The
      complex input impedance of the middle ear, multifrequency admittance
      tympanograms, reflectance patterns (reflectance versus frequency), and
      reflectance tympanograms (reflectance versus ear-canal air pressure) were
      analyzed and compared to human data. The complex impedance of the chinchilla ear
      has a lower stiffness reactance at low frequencies, a higher mass reactance at
      high frequencies, and a lower resistance compared to the human. Multifrequency
      admittance tympanograms from chinchillas follow the same sequence of patterns as
      humans for low frequencies (<2 kHz). At higher frequencies tympanograms from both
      species are poorly organized and do not follow a consistent sequence of patterns.
      Reflectance patterns of chinchillas and humans are different. However, both
      species show high reflectance at low frequencies, regions of lower reflectance in
      mid-frequencies (2-6 kHz), and high reflectance at high frequencies (>8 kHz).
      Reflectance tympanograms for the two species show a single, centrally located
      minimum at low frequencies (<2 kHz) and are substantially different at higher
      frequencies. Results are shown for two animals that underwent eustachian tube
      obstruction. Reflectance patterns obtained with different ear-canal air pressures
      are substantially different. Reflectance results at any single ear-canal pressure
      (including ambient pressure) do not completely characterize the effects of middle
      ear pathology.

PMID- 11572357
TI  - Maturation of the human cochlear amplifier: distortion product otoacoustic
      emission suppression tuning curves recorded at low and high primary tone levels.
AB  - The cochlear amplifier shows level-dependent function and works optimally at low
      levels. For this reason, manipulation of stimulus level is a route through which
      the human cochlear amplifier can be investigated in a noninvasive manner.
      Distortion product otoacoustic emissions (DPOAEs) evoked as a function of
      stimulus level provide a tool for exploration of human cochlear amplifier
      function and, when applied to neonates, for investigation of cochlear maturation.
      The current experiment generated 2f1-f2 DPOAE ipsilateral suppression tuning
      curves (STCs) at three primary tone levels and five f2 frequencies in a large
      group of premature and term neonates and adults. The differences between tuning
      generated with low- and high-level primary tones was measured to provide a gross
      estimate of the "tuning enhancement effect" attributed to the cochlear amplifier.
      Other features of the DPOAE suppression tuning curves were measured as well.
      Consistent with previous reports, at 1500 and 6000 Hz, STCs were narrower, with a
      steeper slope on the low-frequency flank of the tuning curve in premature
      neonates versus adults. Additionally, only DPOAE STCs from adults and term
      neonates became markedly broader and more shallow when recorded with high-level
      primary tones. It has been hypothesized that the excessive narrowness of
      suppression tuning and the absence of a level effect on DPOAE STCs recorded in
      premature neonates reflects a subtle immaturity in cochlear amplifier function
      just prior to term birth.

PMID- 11572358
TI  - Origin of cubic difference tones generated by high-intensity stimuli: effect of
      ischemia and auditory fatigue on the gerbil cochlea.
AB  - Cubic difference tone (CDT) otoacoustic emissions are thought to arise from the
      feedback loop allowing outer hair cells to enhance the sensitivity and tuning of
      the organ of Corti. The existence of residual CDTs during complete cochlear
      ischemia is therefore disturbing. That stimulus intensities must exceed 50-60 dB
      SPL for residual CDTs to be recorded and for level notches to be present in CDT
      growth functions is often cited as evidence for a two-component, "active/passive"
      model: one component, the residual one, would originate from a passive, hardly
      vulnerable mechanism and thus be unsuitable for hearing screening purposes. This
      model was probed in gerbil ears after complete interruption of the cochlear blood
      flow. Cochlear potentials and CDTs were controlled simultaneously through
      continuous monitoring of CDT level and phase for 50 and 60 dB SPL stimuli and
      group-delay measurements. After a clear initial decay, CDT levels elicited at 60
      dB SPL plateaued for several minutes at about 20 dB below initial level, and when
      early level notches were observed, CDT phase changes remained minor. The CDT
      group delays decreased by less than 30%. Later CDT level notches were associated
      with sharp phase reversals but the similarity between CDT characteristics before
      and after a notch was hardly consistent with a two-component interpretation. When
      mild sound overexposure (pure tone, 90-95 dB SPL, 15-30 min) had been performed
      prior to ischemia, little or no ischemic CDT came from the frequency bands where
      auditory fatigue had been detected (within 1 kHz), irrespective of the stimulus
      intensity. It suggests that instead of being passive, residual ischemic CDTs were
      vulnerable and produced according to a near-normal tonotopy by the same
      mechanisms that were sensitive to auditory fatigue. All the results lined up with
      a simple feedback model of cochlear function assuming a single CDT source related
      to mechano-electrical transduction in outer hair cells. More parsimonious than a
      two-component model, it posits that although early stages of ischemia
      dramatically impair the overall performance of the cochlea, the nonlinear
      mechanical stages responsible for the existence of CDTs keep working albeit at
      higher intensities.

PMID- 11572359
TI  - A level of stimulus representation model for auditory detection and attention.
AB  - A model is offered here to address an asymmetry of cueing in signal detection
      [Hafter et al. (1992)] where the effect of frequency uncertainty on the detection
      of a randomly chosen tone was ameliorated by cueing with a sequence of its
      harmonics, but detection of a randomly chosen sequence of harmonics was not
      improved by cueing with their fundamental. The model proposes that signal
      detection can be based on various levels of neural representation that, for the
      case at hand, refer to levels organized either by frequency or by complex pitch.
      Experiments offered to test the model used three-tone complexes for both cues and
      signals. These stimuli consisted of either three randomly chosen frequencies or
      three randomly chosen harmonics (from the set 2 f1 to 7 f1) of a randomly chosen
      fundamental. Support for the idea of cueing and detection at different levels of
      representation was found in higher performance with uncued detection of harmonic
      complexes relative to that found with complexes of unrelated tones and by
      successful cueing of each type of information with cues created to remove
      uncertainty about the relevant information. A final comparison suggests
      independence of performance (presumably of the limiting noise) at each of the
      putative levels of representation.

PMID- 11572360
TI  - Melody recognition using three types of dichotic-pitch stimulus.
AB  - The recognition of 10 different 16-note melodies, constructed using either
      dichotic-pitch stimuli or diotic pure-tone stimuli, was measured. The dichotic
      pitches were created by placing a frequency-dependent transition in the
      interaural phase of a noise burst. Three different configurations for the
      transition were used in order to give Huggins pitch, binaural-edge pitch, and
      binaural-coherence-edge pitch. Forty-nine inexperienced listeners participated.
      The melodies evoked by the dichotic stimuli were consistently identified well in
      the first block of trials, indicating that the sensation of dichotic pitch was
      relatively immediate and did not require prolonged listening experience. There
      were only small improvements across blocks of trials. The mean scores were 97%
      (pure tones), 93% (Huggins pitch), 89% (binaural-edge pitch), and 77% (binaural
      coherence-edge pitch). All pairwise differences were statistically significant,
      indicating that Huggins pitch was the most salient of the dichotic pitches and
      binaural-coherence-edge pitch was weakest. To account for these differences in
      salience, a simulation of lateral inhibition was applied to the recovered
      spectrum generated by the modified equalization cancellation model [J. F.
      Culling, A. Q. Summerfield, and D. H. Marshall, J. Acoust. Soc. Am. 103, 3509
      3526 (1998)]. The height of the peak in the resulting "edge-enhanced" recovered
      spectrum reflected the relative strength of the different dichotic pitches.

PMID- 11572361
TI  - Peripheral auditory processing and investigations of the "precedence effect"
      which utilize successive transient stimuli.
AB  - This article addresses how a consideration of peripheral auditory processing can
      help to understand experiments concerning binaural precedence that employ
      successive binaural transients. It appears that much of the patterning of the
      behavioral data is amenable to an explanation based on peripheral interactions
      that result from auditory filtering and the functioning of auditory hair cells in
      combination with a binaural model based on cross correlation. A noteworthy aspect
      of this approach is that it does not include inhibitory mechanisms like those
      commonly invoked to explain binaural precedence.

PMID- 11572362
TI  - Loudness summation for pulsatile electrical stimulation of the cochlea: effects
      of rate, electrode separation, level, and mode of stimulation.
AB  - The aim of these two experiments was to gain systematic data on the amount of
      loudness summation measured for dual-electrode stimuli with varying temporal and
      spatial separation of current pulses. Loudness summation is important in the
      implementation of speech processing strategies for implantees. However, the
      loudness mapping functions used in current speech processors utilize
      psychophysical data (thresholds and comfortable loudness levels) derived using
      single-electrode stimuli, and do not take into account the temporal and spatial
      patterns of the speech processor output. In the first experiment, the current
      reduction required to equalize the loudness of a dual-electrode stimulus to that
      of its component (and equally loud) single-electrode stimuli was measured for
      three electrode separations (0.75, 2.25, and 7.5 mm), three repetition rates
      (250, 500, and 1000 Hz), and two loudness levels (comfortably loud, and mid
      dynamic range). It was found that electrode separation had little effect on
      loudness summation, except for interactions with level and rate effects at the
      smallest separation. More current adjustment (in dB) was required for higher
      rates and lower levels of stimulation. The second experiment investigated the
      effects of mode (monopolar versus bipolar) and pulse duration on loudness
      summation. More current adjustment was required in bipolar mode than in monopolar
      mode at the lower level only. The main effects in both experiments, and their
      interactions, are consistent with a loudness model in which the neural excitation
      density is first obtained by temporal integration of excitation at each cochlear
      place, then converted to specific loudness via a nonlinear relationship, and
      finally integrated over cochlear place to obtain the loudness. The two important
      features which affect the loudness relationships in dual-electrode stimulation in
      this model are the shape of the excitation density function and the amount by
      which the neural spike probability per pulse is reduced in areas of overlapping
      excitation due to refractory effects.

PMID- 11572363
TI  - Reconciling frequency selectivity and phase effects in masking.
AB  - The effects of auditory frequency selectivity and phase response on masking were
      studied using harmonic tone complex maskers with a 100-Hz fundamental frequency.
      Positive and negative Schroeder-phase complexes (m+ and m-), were used as maskers
      and the signal was a long-duration sinusoid. In the first experiment, thresholds
      for signal frequencies of 1 and 4 kHz were measured as a function of masker
      bandwidth and number of components. A large difference in thresholds between the
      m+ and m- complexes was found only when masker components were presented
      ipsilateral to the signal over a frequency range wider than the traditional
      critical band, regardless of the absolute number of components. In the second
      experiment, frequency selectivity was measured in harmonic tone complexes with
      fixed or random phases as well as in noise, using a variant of the notched-noise
      method with a fixed masker level. The data showed that frequency selectivity is
      not affected by masker type, indicating that the wide listening bandwidth
      suggested by the first experiment cannot be ascribed to broader effective filters
      in complex-tone maskers than in noise maskers. The third experiment employed a
      novel method of measuring frequency selectivity, which has the advantage that the
      overall level at the input and the output of the auditory filter remains roughly
      constant across all conditions. The auditory filter bandwidth measured using this
      method was wider than that measured in the second experiment, but may still be an
      underestimate, due to the effects of off-frequency listening. The data were
      modeled using a single-channel model with various initial filters. The main
      findings from the simulations were: (1) the magnitude response of the Gammatone
      filter is too narrow to account for the phase effects observed in the data; (2)
      none of the other filters currently used in auditory models can account for both
      frequency selectivity and phase effects in masking; (3) the Gammachirp filter can
      be made to provide a good account of the data by altering its phase response. The
      final conclusion suggests that masker phase effects can be accounted for with a
      single-channel model, while still remaining consistent with measures of frequency
      selectivity: effects that appear to involve broadband processing do not
      necessarily require across-channel mechanisms.

PMID- 11572364
TI  - Spatial and temporal factors in auditory saltation.
AB  - This report describes three experiments on auditory saltation, studied with click
      stimuli presented at interclick intervals (ICIs) from 30 to 240 ms. In experiment
      1, subjects rated the strength of the saltation illusion evoked by trains of six
      monaural clicks (i.e., three presented to one ear followed by three to the other
      ear), and six dichotic clicks on which were imposed either a 500-micros
      interaural time difference or a 9-dB interaural level difference (ILD). The
      interaural disparity of theclicks was reversed at the midpoint of the train.
      Subjects reported equivalent strengths of saltation for the dichotic clicks, but
      weaker saltation for the monaural ones. These data indicated that saltation is
      supported by dichotic clicks, regardless of the stimulus manipulation used to
      generate the lateralized images. In experiment 2, subjects rated the strength of
      the saltation evoked by six click trains lateralized, in separate trials, by ILDs
      ranging from 9 to 30 dB, and by a train of monaural clicks. In all ILD
      conditions, the level of the clicks at the "quiet" ear was above click-detection
      threshold when presented monaurally. Saltation weakened with increasing ILD, and
      approximated that seen with monaural clicks when the ILD was 30 dB. These data
      indicated that for the range of ICIs used here, saltation weakened as the stimuli
      became more strongly lateralized. In experiment 3, the number of dichotic clicks
      preceding the disparity reversal was, in separate trials, varied from 3 to 10,
      and subjects were asked to detect the presence of spatial stationarity in the
      click train. By plotting the subjective ratings as a function of the length of
      the leading click train, it was shown that the temporal window within which the
      saltation effect operates varies between listeners, but is usually less than
      about 350-400 ms.

PMID- 11572365
TI  - Estimation of viscoelastic shear properties of vocal-fold tissues based on time
      temperature superposition.
AB  - Empirical data on the viscoelastic shear properties of human vocal-fold mucosa
      (cover) were recently reported at relatively low frequency (0.01-15 Hz). For the
      data to become relevant to voice production, attempts have been made to
      parametrize and extrapolate the data to higher frequencies using constitutive
      modeling [Chan and Titze, J. Acoust. Soc. Am. 107, 565-580 (2000)]. This study
      investigated the feasibility of an alternative approach for data extrapolation,
      namely the principle of time-temperature superposition (TTS). TTS is a hybrid
      theoretical-empirical approach widely used by rheologists to estimate the
      viscoelastic properties of polymeric systems at time or frequency scales not
      readily accessible experimentally. It is based on the observation that for many
      polymers, the molecular configurational changes that occur in a given time scale
      at a low temperature correspond to those that occur in a shorter time scale at a
      higher temperature. Using a rotational rheometer, the elastic shear modulus (G')
      and viscous shear modulus (G'') of vocal-fold cover (superficial layer of lamina
      propria) tissue samples were measured at 0.01-15 Hz at relatively low
      temperatures (5 degrees-37 degrees C). Data were empirically shifted according to
      TTS, yielding composite "master curves" for predicting the magnitude of the shear
      moduli at higher frequencies at 37 degrees C. Results showed that TTS may be a
      feasible approach for estimating the viscoelastic shear properties of vocal-fold
      tissues at frequencies of phonation (on the order of 100-1000 Hz).

PMID- 11572366
TI  - Effects of oscillation of a mechanical hemilarynx model on mean transglottal
      pressures and flows.
AB  - This study introduces a mechanical model of the larynx for investigating dynamic
      aerodynamic effects of phonation. The model mimics the hemilarynx. The tracheal
      inlet section was rectangular (25-mm width, 20-mm height). The vocal fold was
      fabricated with precision machinery from hard plastic with an attached
      oscillating plunger. A speaker assembly and audio amplifier drove the plunger,
      mimicking one-dimensional vocal-fold motion toward a flat wall. The glottal shape
      was rectangular. The glottal diameter was well specified or dynamically followed
      with a laser system. The air was sucked through the channel using a vacuum with
      controlled speed. Frequency and amplitude of the glottis were varied. The mean
      pressure and mean flow data were recorded. For steady-flow conditions, the
      glottal gap ranged from 0.39 to 2.58 mm. The pressure coefficient for steady flow
      had a range of 3.1 to 1.3 for Reynolds numbers between 300 and 9000. For
      oscillation conditions (a) the frequency was varied from 75 to 150 Hz while the
      amplitude was held relatively constant, and (b) the amplitude was varied to 0.3
      mm for a fixed frequency of 100 Hz. The results indicate that the hemilarynx
      model provides mean pressure-flow data similar in form to other models with two
      vocal folds. Furthermore, the dimensional and non-dimensional pressure
      coefficient is sensitive to variations in glottal gap and glottal amplitude, but
      relatively insensitive to the frequency of oscillation.

PMID- 11572367
TI  - An inverse dynamics approach to face animation.
AB  - Muscle-based models of the human face produce high quality animation but rely on
      recorded muscle activity signals or synthetic muscle signals that are often
      derived by trial and error. This paper presents a dynamic inversion of a muscle
      based model (Lucero and Munhall, 1999) that permits the animation to be created
      from kinematic recordings of facial movements. Using a nonlinear optimizer
      (Powell's algorithm), the inversion produces a muscle activity set for seven
      muscles in the lower face that minimize the root mean square error between
      kinematic data recorded with OPTOTRAK and the corresponding nodes of the modeled
      facial mesh. This inverted muscle activity is then used to animate the facial
      model. In three tests of the inversion, strong correlations were observed for
      kinematics produced from synthetic muscle activity, for OPTOTRAK kinematics
      recorded from a talker for whom the facial model is morphologically adapted and
      finally for another talker with the model morphology adapted to a different
      individual. The correspondence between the animation kinematics and the three
      dimensional OPTOTRAK data are very good and the animation is of high quality.
      Because the kinematic to electromyography (EMG) inversion is ill posed, there is
      no relation between the actual EMG and the inverted EMG. The overall redundancy
      of the motor system means that many different EMG patterns can produce the same
      kinematic output.

PMID- 11572368
TI  - The acoustic features of human laughter.
AB  - Remarkably little is known about the acoustic features of laughter. Here,
      acoustic outcomes are reported for 1024 naturally produced laugh bouts recorded
      from 97 young adults as they watched funny video clips. Analyses focused on
      temporal features, production modes, source- and filter-related effects, and
      indexical cues to laugher sex and individual identity. Although a number of
      researchers have previously emphasized stereotypy in laughter, its acoustics were
      found now to be variable and complex. Among the variety of findings reported,
      evident diversity in production modes, remarkable variability in fundamental
      frequency characteristics, and consistent lack of articulation effects in
      supralaryngeal filtering are of particular interest. In addition, formant-related
      filtering effects were found to be disproportionately important as acoustic
      correlates of laugher sex and individual identity. These outcomes are examined in
      light of existing data concerning laugh acoustics, as well as a number of
      hypotheses and conjectures previously advanced about this species-typical vocal
      signal.

PMID- 11572369
TI  - Challenging the notion of innate phonetic boundaries.
AB  - Numerous studies of infants' speech perception abilities have demonstrated that
      these young listeners have access to acoustic detail in the speech signal.
      Because these studies have used stimuli that could be described in terms of adult
      defined phonetic categories, authors have concluded that infants innately
      recognize stimuli as members of these categories, as adults do. In fact, the
      predominant, current view of speech perception holds that infants are born with
      sensitivities for the universal set of phonetic boundaries, and that those
      boundaries supported by the ambient language are maintained, while those not
      supported by the ambient language dissolve. In this study, discrimination
      abilities of 46 infants and 75 3-year-olds were measured for several phonetic
      contrasts occurring in their native language, using natural and synthetic speech.
      The proportion of children who were able to discriminate any given contrast
      varied across contrasts, and no one contrast was discriminated by anything close
      to all of the children. While these results did not differ from those reported by
      others, the interpretation here is that we should reconsider the notion of innate
      phonetic categories and/or boundaries. Moreover, success rates did not differ for
      natural and synthetic speech, and so a minor conclusion was that children are not
      adversely affected by the use of synthetic stimuli in speech experiments.

PMID- 11572370
TI  - A robust method to study stress "deafness".
AB  - Previous research by Dupoux et al. [J. Memory Lang. 36, 406-421 (1997)] has shown
      that French participants, as opposed to Spanish participants, have difficulties
      in distinguishing nonwords that differ only in the location of stress. Contrary
      to Spanish, French does not have contrastive stress, and French participants are
      "deaf" to stress contrasts. The experimental paradigm used by Dupoux et al.
      (speeded ABX) yielded significant group differences, but did not allow for a
      sorting of individuals according to their stress "deafness." Individual
      assessment is crucial to study special populations, such as bilinguals or trained
      monolinguals. In this paper, a more robust paradigm based on a short-term memory
      sequence repetition task is proposed. In five French-Spanish cross-linguistic
      experiments, stress "deafness" is shown to crucially depend upon a combination of
      memory load and phonetic variability in F0. In experiments 3 and 4,
      nonoverlapping distribution of individual results for French and Spanish
      participants is observed. The paradigm is thus appropriate for assessing stress
      deafness in individual participants.

PMID- 11572371
TI  - Minimum spectral contrast needed for vowel identification by normal hearing and
      cochlear implant listeners.
AB  - The minimum spectral contrast needed for vowel identification by normal-hearing
      and cochlear implant listeners was determined in this study. In experiment 1, a
      spectral modification algorithm was used that manipulated the channel amplitudes
      extracted from a 6-channel continuous interleaved sampling (CIS) processor to
      have a 1-10 dB spectral contrast. The spectrally modified amplitudes of eight
      natural vowels were presented to six Med-EI/CIS-link users for identification.
      Results showed that subjects required a 4-6 dB contrast to identify vowels with
      relatively high accuracy. A 4-6 dB contrast was needed independent of the
      individual subject's dynamic range (range 9-28 dB). Some cochlear implant (CI)
      users obtained significantly higher scores with vowels enhanced to 6 dB contrast
      compared to the original, unenhanced vowels, suggesting that spectral contrast
      enhancement can improve the vowel identification scores for some CI users. To
      determine whether the minimum spectral contrast needed for vowel identification
      was dependent on spectral resolution (number of channels available), vowels were
      processed in experiment 2 through n (n =4, 6, 8, 12) channels, and synthesized as
      a linear combination of n sine waves with amplitudes manipulated to have a 1-20
      dB spectral contrast. For vowels processed through 4 channels, normal-hearing
      listeners needed a 6 dB contrast, for 6 and 8 channels a 4 dB contrast was
      needed, consistent with our findings with CI listeners, and for 12 channels a 1
      dB contrast was sufficient to achieve high accuracy (>80%). The above-mentioned
      findings with normal-hearing listeners suggest that when the spectral resolution
      is poor, a larger spectral contrast is needed for vowel identification.
      Conversely, when the spectral resolution is fine, a small spectral contrast (1
      dB) is sufficient. The high identification score (82%) achieved with 1 dB
      contrast was significantly higher than any of the scores reported in the
      literature using synthetic vowels, and this can be attributed to the fact that we
      used natural vowels which contained duration and spectral cues (e.g., formant
      movements) present in fluent speech. The outcomes of experiments 1 and 2, taken
      together, suggest that CI listeners need a larger spectral contrast (4-6 dB) than
      normal-hearing listeners to achieve high recognition accuracy, not because of the
      limited dynamic range, but because of the limited spectral resolution.

PMID- 11572372
TI  - On the upper cutoff frequency of the auditory critical-band envelope detectors in
      the context of speech perception.
AB  - Studies in neurophysiology and in psychophysics provide evidence for the
      existence of temporal integration mechanisms in the auditory system. These
      auditory mechanisms may be viewed as "detectors," parametrized by their cutoff
      frequencies. There is an interest in quantifying those cutoff frequencies by
      direct psychophysical measurement, in particular for tasks that are related to
      speech perception. In this study, the inherent difficulties in synthesizing
      speech signals with prescribed temporal envelope bandwidth at the output of the
      listener's cochlea have been identified. In order to circumvent these
      difficulties, a dichotic synthesis technique is suggested with interleaving
      critical-band envelopes. This technique is capable of producing signals which
      generate cochlear temporal envelopes with prescribed bandwidth. Moreover, for
      unsmoothed envelopes, the synthetic signal is perceptually indistinguishable from
      the original. With this technique established, psychophysical experiments have
      been conducted to quantify the upper cutoff frequency of the auditory critical
      band envelope detectors at threshold, using high-quality, wideband speech signals
      (bandwidth of 7 kHz) as test stimuli. These experiments show that in order to
      preserve speech quality (i.e., for inaudible distortions), the minimum bandwidth
      of the envelope information for a given auditory channel is considerably smaller
      than a critical-band bandwidth (roughly one-half of one critical band).
      Difficulties encountered in using the dichotic synthesis technique to measure the
      cutoff frequencies relevant to intelligibility of speech signals with fair
      quality levels (e.g., above MOS level 3) are also discussed.

PMID- 11572373
TI  - A probabilistic union model with automatic order selection for noisy speech
      recognition.
AB  - A critical issue in exploiting the potential of the sub-band-based approach to
      robust speech recognition is the method of combining the sub-band observations,
      for selecting the bands unaffected by noise. A new method for this purpose, i.e.,
      the probabilistic union model, was recently introduced. This model has been shown
      to be capable of dealing with band-limited corruption, requiring no knowledge
      about the band position and statistical distribution of the noise. A parameter
      within the model, which we call its order, gives the best results when it equals
      the number of noisy bands. Since this information may not be available in
      practice, in this paper we introduce an automatic algorithm for selecting the
      order, based on the state duration pattern generated by the hidden Markov model
      (HMM). The algorithm has been tested on the TIDIGITS database corrupted by
      various types of additive band-limited noise with unknown noisy bands. The
      results have shown that the union model equipped with the new algorithm can
      achieve a recognition performance similar to that achieved when the number of
      noisy bands is known. The results show a very significant improvement over the
      traditional full-band model, without requiring prior information on either the
      position or the number of noisy bands. The principle of the algorithm for
      selecting the order based on state duration may also be applied to other sub-band
      combination methods.

PMID- 11572374
TI  - Effects of relative phases on pitch and timbre in the piano bass range.
AB  - Piano bass tones raise questions related to the perception of multicomponent,
      inharmonic tones. In this study, the influence of the relative phases among
      partials on pitch and timbre was investigated for synthesized bass tones with
      piano-like inharmonicity. Three sets of bass tones (A0 = 27.5 Hz, 100 partials,
      flat spectral envelope) were generated; harmonic, low inharmonic, and high
      inharmonic. For each set, five starting phase relations among partials were
      applied; sine phases, alternate (sine/cosine) phases, random phases, Schroeder
      phases, and negative Schroeder phases. The pitch and timbre of the tones were
      influenced markedly by the starting phases. Listening tests showed that listeners
      are able to discriminate between tones having different starting phase relations,
      and also that the pitch could be changed by manipulating the relative phases
      (octave, fifth, major third). A piano-like inharmonicity gives a characteristic
      randomizing effect of the phase relations over time in tones starting with
      nonrandom phase relations. A measure of the regularity of the phase differences
      between adjacent partials is suggested for quantifying this randomization
      process. The observed phase effects might be of importance in synthesizing,
      recording, and reproducing piano music.

PMID- 11572375
TI  - Vocal intensity in falsetto phonation of a countertenor: an analysis by synthesis
      approach.
AB  - An analysis by synthesis paradigm was implemented to model glottal airflow and
      vocal tract acoustics for the falsetto phonation of a trained countertenor.
      Changes in vocal intensity were measured as a function of subglottal pressure,
      open quotient of the time-varying glottal airflow pulse, and formant tuning. The
      contributions of laryngeal adduction (open quotient of the glottal flow pulse)
      and of formant tuning to intensity change were derived from modeled data. The
      findings were: (1) Subglottal pressure accounted for almost 90% of the variation
      in SPL in falsetto phonation. (2) The open quotient of the glottal flow pulse was
      remarkably constant in these falsetto phonations, and thus did not affect vocal
      intensity significantly. (3) Formant tuning occurred in two out of nine
      possibilities for the vowel /a/. These instances did not support the concept of
      systematic exploitation of formant tuning.

PMID- 11572376
TI  - Temperature dependence of ultrasonic enhancement with a site-targeted contrast
      agent.
AB  - Molecular imaging contrast agents specifically detect the biochemical
      "signatures" of disease before anatomical manifestations are apparent. Sensitive
      and specific localization of fibrin both in vivo and in vitro has been
      demonstrated with the use of a ligand-directed liquid perfluorocarbon
      nanoparticle. Since the acoustic properties of perfluorocarbons are known to vary
      with temperature, it was hypothesized that temperature could be used to augment
      the magnitude of enhancement imparted by targeted nanoparticles. Accordingly, the
      acoustic backscatter of two different substrates, nitrocellulose membrane and
      human plasma clot, targeted by the nanoparticles was measured at temperatures
      ranging from 27 degrees to 47 degrees C in 5 degrees C increments. Classic avidin
      biotin interactions were utilized to couple biotinylated nanoparticles to avidin
      conjugated nitrocellulose membranes. Ultrasonic contrast enhancement of the
      nitrocellulose membrane at 25 MHz, measured by acoustic microscopy, increased
      from 2.0+/-0.3 dB at 27 degrees C to 3.7+/-0.4 at 47 degrees C. In a similar
      experiment, antifibrin nanoparticles bound to human plasma clots also exhibited
      temperature-dependent ultrasonic signal enhancement ranging from 13.9+/-1.5 dB at
      27 degrees C to 18.1+/-1.5 dB at 47 degrees C. The increase in ultrasonic
      contrast enhancement measured was well described by a simple, acoustic
      transmission line model with temperature-dependent impedance. These results
      suggest that temperature-dependent changes in acoustic backscatter may be used to
      further differentiate tissues targeted with site-specific nanoparticles from
      surrounding normal soft tissues.

PMID- 11572377
TI  - Use of a dual-pulse lithotripter to generate a localized and intensified
      cavitation field.
AB  - Localizing cavitation to the kidney stone in extracorporeal shock wave
      lithotripsy may be desirable since cavitation appears to play a major role in
      both stone comminution and renal tissue damage. A method has been developed to
      localize and intensify cavitation damage in vitro. Cavitation fields in water
      were filmed with a high-speed digital video camera. In a conventional
      lithotripter (CL), the shock wave produced by a single source creates a 2 x 10 cm
      cylindrical cloud of bubbles in water. Bubbles in the CL field collapse
      simultaneously along the focal axis to produce a nearly uniform 1-mm x 8-cm line
      of pits in 25-microm-thick aluminum foil. Our dual-pulse lithotripter (DPL) uses
      two shock wave sources, facing each other, confocal, and triggered simultaneously
      to create a 4 x 5 cm cylindrical cloud of bubbles that collapse over a range of
      times and strengths such that the greatest pit damage on foils is contained
      within a few square millimeters of the focus. The time for bubbles to grow and
      collapse was measured with a focused hydrophone and compared with calculations
      based on the Gilmore equation. Pressure doubling due to synchronous arrival of
      the two pulses at the focus created increased bubble growth and increased foil
      pit depth. Asynchronous timing between the two pulses elsewhere in the DPL field
      resulted in disruption of radial dynamics and negligible pitting to foils.
      Translation of bubbles was also investigated, both numerically and
      experimentally. While net translation was calculated to be <0.3 mm in all cases,
      the rapid acceleration of bubbles in a small region may contribute to their
      premature destruction in that region. Overall, radial dynamics were found to be
      largely responsible for the observed pattern of cavitation in the dual-pulse
      lithotripsy field.

PMID- 11572378
TI  - Influence of the pH on the behavior of an imprinted polymeric stationary phase-
      supporting evidence for a binding site model.
AB  - The equilibrium isotherms of the two enantiomers of phenylalanine anilide (PA)
      were measured by conventional frontal analysis at three different pH on a
      thermally-treated imprinted stationary phase selective for the L enantiomer. The
      first of these pH (buffer pH=3.0, pH(app)=4.0) is well below the apparent pKa
      (6.4) of the two solutes, the second (buffer pH=5.8, pH(app)=7.0) slightly below
      this pKa, and the third (buffer pH=7.0, pH(app)=8.3) well above it. The
      experimental data were fitted to several isotherm models. The best estimates of
      the parameters of these models are reported and discussed. The corresponding
      isotherms are compared with the experimental ones. The contributions of the
      enantioselective and nonselective interactions could be separated. The results
      obtained show that the saturation capacity is always smaller for D-PA than for L
      PA, the template. The analytical separation is best at pH=3.0 because of a good
      separation factor (2.82) and short retention times. A good compromise between the
      resolution and the saturation capacity is obtained at pH=5.8, for which the best
      preparative separation is found. Both analytical and preparative results are poor
      at pH=7.0 because the separation factor is low (1.32). At this pH, the isotherm
      remains nearly linear in the whole concentration range accessible to
      measurements. The number of nonselective sites increases with increasing mobile
      phase pH slightly faster than the number of selective sites, suggesting different
      pKa ranges for the two type of sites. Moreover, the binding energy and the
      homogeneity of the selective sites decreases with increasing pH. These results
      agree with a binding site model involving more than one carboxylic acid group,
      providing charge complementarity and hydrogen bond donors for binding of L-PA.

PMID- 11572379
TI  - Routine analysis of alcohol and nonylphenol polyethoxylates in wastewater and
      sludge using liquid chromatography-electrospray mass spectrometry.
AB  - A wide range of alcohol and nonylphenol polyethoxylates was determined by
      separation on a reversed-phase liquid chromatographic column, followed by
      electrospray ionisation-mass spectral analysis. The compounds were separated
      chromatographically according to their aliphatic chain length. The mass spectral
      analysis functioned as a second separation step during which homologues of the
      ethoxylates were separated according to their polyethoxylate chain length. In
      this manner a truly orthogonal separation was obtained. The compounds were
      detected as ammonium complexes. The analysis presented is capable of qualitative
      and quantitative determination of a large number of ethoxylates as well as their
      metabolites in a single run. The method was applied to many different sample
      types, ranging from primary and treated wastewater to sludge. Batches of 50 real
      samples were routinely analysed without the need for cleaning the mass
      spectrometer or regeneration of the column. By utilising the extracted mass
      chromatograms, detection limits of 1 to 10 microg/l could be obtained for
      individual compounds in water samples, while the detection limits were around 100
      microg/kg in sludge, depending on the degree of pollution.

PMID- 11572380
TI  - Behavior of n-alkanes on poly(oxyethylene) capillary columns. Evaluation of
      interfacial effects.
AB  - The solvation behavior of n-alkanes on poly(oxyethylene) was studied employing
      capillary gas chromatography. Interfacial effects were discriminated and
      evaluated through the analysis of retention data from six commercial fused-silica
      capillary columns, having film thicknesses of 0.15-5 microm. Expressions for the
      mixed retention mechanism in capillary columns were deduced from assumptions of a
      general character. Partition coefficients were determined for the n-alkanes up to
      28 carbon atoms, at temperatures ranging from 40 to 240 degrees C. In agreement
      with other authors, it was observed that interfacial phenomena contribute poorly
      to the chromatographic retention, being negligible over 140 degrees C for
      homologues with less than 16 carbons.

PMID- 11572381
TI  - Application of the polysilicone fullerene coating for solid-phase microextraction
      in the determination of semi-volatile compounds.
AB  - Solid-phase microextraction using polysilicone fullerene (PF) coating has been
      applied for the determination of semi-volatile compounds. Detection limits at the
      10 ng l(-1) to approximately microg l(-1) level were achieved using flame
      ionization detection. A wide linear range was obtained with precision below 7%
      relative standard deviation. Parameters that affect the extraction process were
      investigated, which included sampling time, desorption time, sampling
      temperature, and salting out effect. Compared to the non-polar commercial
      polydimethylsiloxane (PDMS) coating, the PF coating has higher extraction
      efficiency, better selectivity and greater sensitivity for aromatic compounds.
      The experimental results revealed the thermal stability and life span are
      superior to commercially available PDMS. The PF coating has been demonstrated to
      possess planarity molecular recognition. The theoretical study confirmed that
      quantification is feasible under non-equilibrium conditions by use of the PF
      coating.

PMID- 11572382
TI  - Effect of moisture on the extraction efficiency of polycyclic aromatic
      hydrocarbons from soils under atmospheric pressure by focused microwave-assisted
      extraction.
AB  - The effects of the moisture content in the original, air-dried and re-moistened
      matrices as well as solvent have been studied on the recovery of polycyclic
      aromatic hydrocarbons (PAHs) from soil by a focused microwave-assisted extraction
      (FMAE) method. Solvents selected for the extractions were cyclohexane-acetone
      (1:1), hexane-acetone (1:1) and dichloromethane. On the extraction of 20-day aged
      spiked soil, the highest recovery was found by applying hexane-acetone mixture.
      Spiked soil sample, quality control sample and real soil sample were used for the
      evaluation of moisture effect. It indicated that the presence of water in the
      soil is important for the recovery enhancement of PAHs and with this presence it
      is possible to avoid drying step with the FMAE technique. A comparison between
      microwave and 16-h Soxhlet methods has been made. It evidenced that the microwave
      assisted extraction under ambient atmospheric pressure is a suitable alternative
      to Soxhlet extraction for the analysis of PAHs in soils.

PMID- 11572383
TI  - Construction and validation of automated purge-and-trap-gas chromatography for
      the determination of volatile organic compounds.
AB  - An automated purge-and-trap chromatographic system for the determination of
      dissolved volatile organic compounds in aqueous samples was built in the
      laboratory with minimum cost both in the construction and routine operation. This
      system was built upon a commercial gas chromatograph with full automation
      capability using self-developed hardware and software. The use of a multi-sorbent
      bed quantitatively trapped a wide range of volatile organic compounds at ambient
      temperature, including the extremely volatile ones such as dichlorofluoromethane
      (CFC-12). Flash heating for rapid desorption and adequate plumbing for minimizing
      dead volume resulted in excellent chromatographic separation at above-ambient
      temperatures, which eliminated the need for cryogen for cooling at the head of
      the column, a second refocusing stage, or entire GC oven for refocusing. This
      cryogen-free system was tested with standard solutions and environmental samples
      for determining hydrocarbons with flame ionization detection, and halogenated
      compounds with electron-capture detection. An innovative method was also
      developed for validating the system's linearity for extremely volatile compounds.
      By introducing ambient air, which usually contains constant levels of
      anthropogenic halocarbons, e.g., CFC-12 and CFC-11 (CCl3F), the need to prepare
      aqueous standards containing extremely volatile compounds is avoided, hence
      providing a convenient method for evaluating a purge-and-trap system.

PMID- 11572384
TI  - Bile acids and sterols in urban sewage treatment plants.
AB  - The composition of bile acids, sterols and sterones in water and sludge from an
      urban sewage treatment plant has been examined for assessment of the possible use
      of these compounds as pollution biomarkers. Samples were solvent-extracted,
      hydrolysed, and fractionated by column chromatography to separate acids,
      hydrocarbons, sterones and sterols. These fractions, except hydrocarbons, were
      methylated (acids only) and silylated for instrumental analysis. Gas
      chromatographic-mass spectrometric analysis was performed in the electron-impact
      mode, using a non-polar capillary column. Lithocholic acids (3alpha- and 3beta
      epimers), coprostanone, coprostanol, cholesterol, cholestenone, and cholestanone
      were found in sludge and all waters. However, the waters after secondary plant
      treatment contained mainly lithocholic acids epimers and coprostanone, pointing
      to these compounds as potential markers for urban treatment plant effluents in
      natural waters courses.

PMID- 11572385
TI  - Simultaneous quantitation of nucleoside HIV-1 reverse transcriptase inhibitors by
      short-end injection capillary electrochromatography on a beta-cyclodextrin-bonded
      silica stationary phase.
AB  - As part of our on-going study of the analysis and quantitation of anti-HIV
      nucleosides, a capillary electrochromatography (CEC) method has been developed
      for the simultaneous quantitation of nucleoside HIV reverse transcriptase
      inhibitors (NRTIs), i.e. zidovudine (AZT), lamivudine (3TC), didanosine (ddA) and
      its administrated form (ddI), stavudine (d4T) and hivid (ddC). CEC on chiral
      stationary phase has mainly been dedicated to the separation of enantiomers.
      However, this paper explores an original application of a beta-cyclodextrin
      bonded silica packed column, taking advantage of the internal hydrophobicity of
      the polysaccharide to separate the NRTIs. The influence of several parameters (pH
      buffer, ionic strength, acetonitrile content, temperature and voltage) has been
      investigated using the short-end injection technique to achieve baseline
      separation in a short-time analysis before quantitation.

PMID- 11572386
TI  - Influence of the unpacked section on the chromatographic performance of duplex
      strong anion-exchange columns in capillary electrochromatography.
AB  - This work describes initial investigations of strong anion-exchange (SAX) packing
      materials for capillary electrochromatography (CEC). The use of SAX phases in CEC
      is theoretically appealing for the analysis of negatively charged species. The
      reversed direction of the electroosmotic flow (EOF) generated by SAX phases (in
      comparison to reversed phases and strong cation-exchange phases) means that
      negative species can migrate with the EOF, not against it, hence the analysis
      times, of such species should be decreased and efficiencies improved. Duplex CEC
      columns (the standard for instruments using UV detection) consist of a packed and
      an unpacked section. Using common reversed-phase packing materials the direction
      of the EOF in both sections is co-linear, however when normal fused-silica
      capillaries are packed with SAX material the direction of the EOF in the two
      sections oppose one another. It has been shown, using conventional duplex CEC
      columns and fully packed CEC-MS columns that the opposing direction of EOF causes
      a massive degradation in column performance. Consequentially, it is demonstrated
      that if the EOF in the open section of the duplex SAX column can be controlled
      via pH or capillary derivatisation then good, reproducible CEC can be performed
      on anionic species using SAX packed CEC columns.

PMID- 11572388
TI  - Prediction of internal standards in reversed-phase liquid chromatography. 1.
      Initial study on predicting internal standards for use with neutral samples based
      on linear solvation energy relationships.
AB  - This paper describes the results of an initial study on the application of linear
      solvation energy relationships (LSERs) to the prediction of internal standard
      compounds in reversed-phase liquid chromatographic (RPLC) method development. Six
      neutral samples are separated on an Inertsil ODS(3) column by either acetonitrile
      water or methanol-water mobile phases under either isocratic or linear gradient
      conditions. After the separation conditions are optimized, the desired positions
      for internal standard candidates are selected based on the "open windows" of the
      chromatograms. The compounds with the desired retention range are then predicted
      based on LSERs from a database consisting of more than 700 compounds with defined
      physicochemical properties. The prediction requires the use of LSER coefficients
      under the separation conditions for each sample. They are determined a priori by
      performing multivariable linear regression on the retention of 20 reference
      solutes against their physicochemical properties. It can be concluded from the
      study that LSER is an excellent approach to the selection of internal standard
      compounds for RPLC under either isocratic or gradient elution. The average
      prediction error is usually within 10%, but no more than 20%. Finally, LSER
      approach is fast and systematic, and will save a significant amount of time and
      resources during RPLC method development.

PMID- 11572387
TI  - Analysis of large-volume DNA markers and polymerase chain reaction products by
      capillary electrophoresis in the presence of electroosmotic flow.
AB  - We have demonstrated on-line concentration and separation of DNA in the presence
      of electroosmotic flow (EOF) using poly(ethylene oxide) (PEO) solutions. After
      injecting large-volumes DNA samples, PEO solutions entered a capillary filled
      with 400 mM Tris-borate (TB) buffers by EOF and acted as sieving matrices. DNA
      fragments stacked between the sample zone and PEO solutions. Because sample
      matrixes affected PEO adsorption on the capillary wall, leading to changes in
      EOF, migration time, concentration, and resolving power varied with the injection
      length. When injecting phiX174 RF DNA-HaeIII digest prepared in 5 mM Tris-HCl
      buffer, pH 7.0, at 250 V/cm, peak height increased linearly as a function of
      injection volume up to 0.9 microl (injection time 150 s). The sensitivity
      improvement was 100-fold compare to that injected at 25 V/cm for 10 s (0.006
      microl). When injecting 1.54 microl of GeneScan 1000 ROX, the sensitivity
      improvement was 265-fold. The sensitivity improvement was 40-fold when injecting
      0.17 microl DNA sample containing pBR 322/HaeIII, pBR 328/BglI, and pBR 328/HinfI
      digests prepared in phosphate-buffered saline. This method allows the analysis of
      polymerase chain reaction (PCR) products amplified after 17 cycles when injecting
      0.32 microl (at 30 cm height for 300 s). The total analysis time was shorter
      (91.6 min) than that (119.6 min) obtained from injecting PCR products after 32
      cycles for 10 s.

PMID- 11572389
TI  - Use of a partial filling technique and reverse migrating micelles in the study of
      N-methylcarbamate pesticides by micellar electrokinetic chromatography
      electrospray ionization mass spectrometry.
AB  - This study describes three ways to couple micellar electrokinetic chromatography
      (MEKC) on-line with electrospray ionization mass spectrometry (ESI-MS) for the
      analysis of N-methylcarbamate pesticides. The methods involved the use of a
      partial filling (PF) technique under basic conditions and the use of reverse
      migrating micelles (RMMs) under acidic and basic conditions. The use of RMMs in
      basic electrolyte solutions required coated capillaries with low electroosmotic
      flows, and capillaries coated with anionic poly(sodium 2-acrylamide-2
      methylpropanesulfonate) were selected for the purpose. Before the on-line MEKC
      ESI-MS coupling, the MEKC and MS conditions were separately optimized under off
      line conditions. The methods were compared in terms of detection limits and the
      stability of the electrospray process. The PF method offered good separation but
      poorer stability of the electrospray relative to the other methods. A more stable
      electrospray performance was obtained with use of RMMs in acidic electrolyte
      solutions, but some of the analytes were protonated and could not be detected due
      to the increase in their retention factors. However, with the use of anionic
      polymer-coated capillaries and RMMs at pH 8.5, all analytes were successfully
      separated. The high-salt stacking method was applied to improve the sensitivity
      of MEKC-ESI-MS and the detection limits were in the range of 0.04-2.0 microg/ml.

PMID- 11572390
TI  - Dynamically coated capillaries improve the identification power of capillary zone
      electrophoresis for basic drugs in toxicological analysis.
AB  - In systematic toxicological analysis (STA), analytical methods should have a high
      identification power. This can be suitably expressed by parameters such as mean
      list length (MLL) or discriminating power (DP). The reproducibility of a method
      has a great impact on its identification power, and should be as high as
      possible. In this study, two separation methods based on capillary zone
      electrophoresis (CZE) were evaluated towards STA applications. Besides a normal
      phosphate buffer, the commercially available buffer CElixir was used, which is a
      double-layer dynamic coating system. The coating stabilizes the endoosmotic flow,
      is independent of the pH, and is claimed to be more reproducible and faster at
      low pH than with normal buffers. A test set of 73 basic pharmaceutical compounds
      was analyzed by the two CZE methods. The total analysis time, including rinsing
      steps, was 8 min when the coating was used and 18 min without the coating.
      Effective mobilities were calculated and the reproducibilities were a factor of 2
      better when the coating was used (between-days SD 0.020 and 0.040 m2/V s with and
      without the coating, respectively). MLL and DP were calculated for the two CZE
      methods and for combinations with standardized liquid and gas chromatography
      systems. CZE with CElixir coating clearly has a high potential for STA
      applications, as it was shown to have a higher identification power and shorter
      analysis times than normal CZE.

PMID- 11572391
TI  - Prediction of electrophoretic mobilities of sulfonamides in capillary zone
      electrophoresis using artificial neural networks.
AB  - Artificial neural networks (ANNs) were successfully developed for the modeling
      and prediction of electrophoretic mobility of a series of sulfonamides in
      capillary zone electrophoresis. The cross-validation method was used to evaluate
      the prediction ability of the generated networks. The mobility of sulfonamides as
      positively charged species at low pH and negatively charged species at high pH
      was investigated. The results obtained using neural networks were compared with
      the experimental values as well as with those obtained using the multiple linear
      regression (MLR) technique. Comparison of the results shows the superiority of
      the neural network models over the regression models.

PMID- 11572392
TI  - Separation of chromium (III) and chromium (VI) by capillary electrophoresis using
      2,6-pyridinedicarboxylic acid as a pre-column complexation agent.
AB  - A simple method was developed for the simultaneous determination of Cr(III) and
      Cr(VI) by capillary zone electrophoresis (CZE), where Cr(III) was chelated with
      ligands to form anionic complexes. Nitrilotriacetic acid, N-2
      hydroxyethylenediaminetriacetic acid, ethylenediaminetetraacetic acid,
      diethylenetriaminepentaacetic acid, and 2,6-pyridinedicarboxylic acid (PDCA) were
      investigated as Cr(III) complexing ligands. Of all the ligands studied, 2,6-PDCA
      with Cr(III) gave the largest UV response and high selectivity for Cr(III). In
      addition, the condition for pre-column derivatization, including pH,
      concentration ratio [Cr(III)/2,6-PDCA] and the stability of Cr(III) complexes
      were also examined. The separation of anionic forms of Cr(III) and Cr(VI) was
      achieved using co-CZE with UV detection at 185 nm. The electrolyte contained 30
      mM phosphate, 0.5 mM tetradecyltrimethylammonium bromide, 0.1 mM 2,6-PDCA and 15%
      (v/v) acetonitrile at pH 6.4. The detection limits were 2 microM for Cr(III) and
      3 microM for Cr(VI) and linear plots were obtained in a concentration range of 5
      200 microM. The utility of the method was demonstrated for the determination of
      Cr(III) and Cr(VI) in contaminated soils.

PMID- 11572393
TI  - On-line monitoring of trihalomethanes in drinking water using continuous-flow
      purge and cryofocusing gas chromatography-mass spectrometry.
AB  - A continuous-flow purge-and-trap-GC-MS system was developed for on-line
      monitoring of THMs (trihalomethanes) in drinking water. Three systems with
      different traps and purging flow-rates are discussed. In order to minimize
      interference from water vapor, total purge gas volume and injection temperature
      were controlled during analysis. Shorter sample concentration time and GC
      separation time reduced total cycle time to less than 5 min. The detection limits
      of the system could be lowered to 10 ppt, 25 ppt, 40 ppt, and 50 ppt (w/w) for
      CHCl3, CHCl2Br, CHClBr2, and CHBr3, respectively. This system could detect
      changes in sample concentration when applied to the on-line monitoring of THMs in
      drinking water.

PMID- 11572394
TI  - Practical method for evaluation of linearity and effective pathlength of on
      capillary photometric detectors in capillary electrophoresis.
AB  - The optical characteristics of on-capillary photometric detectors for capillary
      electrophoresis were evaluated and five commercial detectors were compared. Plots
      of sensitivity (absorbance/concentration) versus absorbance obtained with a
      suitable testing solution yield both the linear range and the effective path
      length of the detector. The detector linearity is a crucial parameter when using
      absorbing electrolytes, such as for indirect photometric detection, and
      especially for highly absorbing electrolyte probe ions. The upper limits of the
      linear ranges (determined as 5% decline in sensitivity) for five commercial
      detectors ranged from 0.175 to 1.2 AU. The effective pathlength reflects the
      quality of the optical design of the detector and is equal to the capillary
      internal diameter only for a light beam passing exactly through the capillary
      centre, but becomes progressively shorter for imperfect optical designs. The
      determined effective pathlength for the five investigated detectors ranged from
      49.7 to 64.6 microm for a 75 microm I.D. capillary.

PMID- 11572395
TI  - Study of the stability of cellulose-holocellulose solutions in N,N
      dimethylacetamide-lithium chloride by size exclusion chromatography.
AB  - Solutions in N,N-dimethylacetamide (DMAC)-LiCl were prepared from two different
      pulps (sulphite pulp from softwood and cotton linters) in different ageing
      states. Degradation of the stirred solutions at 35-40 degrees C was observed by
      determining the molecular masses by size exclusion chromatography (SEC). We
      showed that under these conditions cellulose and holocelluloses are degraded in
      DMAC-LiCl and that the rate of degradation is dependent on the temperature and
      the initial state of degradation of the sample. Temperature and dissolution time
      are recommended to be reduced, especially for aged samples.

PMID- 11572396
TI  - Assay of 2,3-dihydroxybenzoic acid and related compounds in plant materials by
      high-performance liquid chromatography.
AB  - Salicylic acid and its putative biosynthetic precursors were assayed
      isocratically by RP-HPLC with UV detection at 280 nm. Optimum resolution was
      provided by an HPLC mobile phase consisting of MeOH-1% aqueous HOAc (40:60, v/v),
      at pH 4. Furthermore, for the analysis of 2,3-dihydroxybenzoic acid (2,3-DHBA) in
      Catharanthus roseus cell cultures after elicitation, a mobile phase consisting of
      acetonitrile-1% aqueous HCOOH containing 0.25% trichloroacetic acid (1:5, v/v),
      at pH 2, was used. The recovery for the free form of 2,3-DHBA was about 80% after
      a one-step extraction of the cells. The detection limit of 2,3-DHBA was 3 microg
      by using saligenin as an internal standard.

PMID- 11572397
TI  - Effect of mobile phase acidic additives on enantioselectivity for phenylalanine
      analogs.
AB  - The use of acidic mobile phase additives allows the chiral separation of
      underivatized phenylalanine analogs on a common amylosic column. In addition to
      decreasing retention and band-broadening arising from non-ideal interactions,
      acidic additives may also increase selectivity. This appears to be due to the
      minimization of non-selective binding in the recognition site. Effects of the
      additives are related to additive pKa and size. Ethanesulfonic acid was typically
      the most effective additive with trifluoroacetic acid being one of the least
      effective.

PMID- 11572398
TI  - Effect of mobile phase amine additives on enantioselectivity for phenylalanine
      analogs.
AB  - The use of basic mobile phase additives enhances the chiral separation of
      underivatized phenylalanine analogs on a common amylosic column. These additives
      appear to exert their effect through differential disruption of hydrogen binding
      involved in the recognition process. Several examples of amine increasing
      retention of the second eluting enantiomer while decreasing retention of the
      other enantiomer were observed. This gave dramatically increased selectivity and
      was most commonly observed with cyclopropylamine and cyclobutylamine. The effect
      was attributed to steric factors involved in the elution process.

PMID- 11572399
TI  - Affinity-reversed-phase liquid chromatography assay to quantitate recombinant
      antibodies and antibody fragments in fermentation broth.
AB  - An automated dual-column liquid chromatography assay comprised of affinity and
      reversed-phase separations that quantifies the majority of antibody-related
      protein species found in crude cell extracts of recombinant origin is described.
      Although potentially applicable to any antibody preparation, we here use samples
      of anti-CD18 (Fab'2LZ) and a full-length antibody, anti-tissue factor (anti-TF),
      from various stages throughout a biopharmaceutical production process to describe
      the assay details. The targeted proteins were captured on an affinity column
      containing an anti-light-chain (kappa) Fab antibody (AME5) immobilized on
      controlled pore glass. The affinity column was placed in-line with a reversed
      phase column and the captured components were transferred by elution with dilute
      acid and subsequently resolved by eluting the reversed-phase column with a
      shallow acetonitrile gradient. Characterization of the resolved components showed
      that most antibody fragment preparations contained a light-chain fragment, free
      light chain, light-chain dimer and multiple forms of Fab'. Analysis of full
      length antibody preparations also resolved these fragments as well as a
      completely assembled form. Co-eluting with the full-length antibody were high
      molecular-mass variants that were missing one or both light chains. Resolved
      components were quantified by comparison with peak areas of similarly treated
      standards. By comparing the two-dimensional polyacrylamide gel electrophoresis
      patterns of an Escherichia coli blank run, a production run and the material
      affinity captured (AME5) from a production run, it was determined that the AME5
      antibody captured isoforms of light chain, light chain covalently attached to
      heavy chain, and truncated light chain isoforms. These forms comprise the bulk of
      the soluble product-related fragments found in E. coli cell extracts of
      recombinantly produced antibody fragments.

PMID- 11572400
TI  - Homogeneous fluorescent derivatization of large proteins.
AB  - A method of homogeneously derivatizing large proteins for highly sensitive
      analysis is described. Homogeneity of the derivative was realized by tagging all
      the free amino groups of proteins. With this method, alpha-chymotrypsinogen A,
      ovalbumin and bovine serum albumin were derivatized with 6-aminoquinolyl-N
      hydroxysuccinimidyl carbamate (AQC). Prior to the derivatization, all the
      proteins were reduced and alkylated. After reacting the resulting unfolded
      proteins with excessive amounts of AQC, the samples were analyzed with matrix
      assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF
      MS) to determine the derivatization degree. The results indicated that all three
      proteins had been, or had almost been, fully derivatized. HPLC and CE were used
      for characterizing these protein derivatives. Under the optimized fluorescence
      detection conditions, the detectability of the tagged proteins was 2400-6200
      times better than that detected at UV 280 nm, 170-300 times better than detected
      at UV 214 nm, and 150-420 times better than measured with their native
      fluorescence.

PMID- 11572401
TI  - Versatile two-phase solvent system for alkaloid separation by high-speed counter
      current chromatography.
AB  - In order to find a versatile high speed counter-current chromatography solvent
      system that can be used as a general prefractionation system for most alkaloids,
      the crude extracts of five Chinese traditional medicinal herbs, Cortex
      phellodendri, Semen strychni, green tea, Sophora flavescens ait, and Datura mete
      L. were resolved. All separations were performed only with a two-phase system
      composed of CHCl3-CH3OH-water (4:3:2). The water had different acidities
      controlled by adding NaH2PO4 or HCl to each sample. The fractionated components
      were identified by thin-layer chromatography, which confirmed this solvent system
      was versatile and very useful for the separation of alkaloids.

PMID- 11572402
TI  - Characterization of an unknown component in Noscapine using liquid chromatography
      mass spectrometry and proton nuclear magnetic resonance spectroscopy.
AB  - Analytical and semipreparative LC methods were used to quantitate and isolate an
      unknown component (Impurity A) found in samples of bulk Noscapine. This component
      was also examined by LC-ESI-MS and 1H-NMR. It was concluded that the structure of
      Impurity A only differed from Noscapine in that it possessed a hydroxyl group at
      position 21 of the isobenzofuranone moiety.

PMID- 11572403
TI  - Ethnic health, "ecological balance," the environment, and genes.

PMID- 11572404
TI  - An investigation of health behavior change in Vietnamese-born individuals living
      in Sydney, Australia.
AB  - OBJECTIVE: The purpose of this study was to look at rates of acculturation among
      Vietnamese immigrants, with particular emphasis on health behaviors. DESIGN: A
      volunteer sample was surveyed. SETTING/PARTICIPANTS: The participants were drawn
      from inner and western Sydney, Australia. Participants were asked for their
      perception of their English fluency as a measure of likely exposure to health
      promotion advertising and their food, social, exercise, drinking, and smoking
      habits. RESULTS: It was found that the longer the Vietnamese immigrants
      participants had lived in Australia, the less likely they were to smoke; in fact,
      the smoking rate of this population is as low as that of the Australian
      population as a whole. However the immigrants did not change their low rate of
      alcohol consumption. In addition, the Vietnamese who had lived longer in
      Australia significantly increased their daily exercise and started to eat more
      take-away foods. CONCLUSIONS: With respect to health promotion, these changes are
      mixed: smoking has decreased, but half the group had begun eating take-away
      foods; this factor, if combined with a lack of exercise, is likely to lead to
      obesity.

PMID- 11572405
TI  - Psychosocial risk factors for coronary disease in White, South Asian and Afro
      Caribbean civil servants: the Whitehall II study.
AB  - BACKGROUND: Psychosocial factors are associated with the etiology and prognosis
      of coronary heart disease (CHD) in White populations; however, previous studies
      have not examined the distribution of psychosocial factors in ethnic groups with
      coronary rates higher (South Asian) and lower (Afro-Caribbean) than those of
      Whites. STUDY OBJECTIVE: To determine whether ethnic differences in psychosocial
      risk factors parallel those in CHD mortality. DESIGN: Cross-sectional survey.
      SETTING: 20 civil service departments in London. PARTICIPANTS: 8973 White, 577
      South Asian, and 360 Afro-Caribbean office-based civil servants, aged 35-55
      years. OUTCOME MEASURES: Minor psychiatric morbidity (General Health
      Questionnaire), social supports (marital status, social networks, negative
      aspects of support, confiding/emotional support, social support at work),
      psychosocial work characteristics (job control, effort-reward imbalance),
      hostility levels and presence of Type A personality. RESULTS: South Asians,
      compared to Whites, had more depression, higher negative supports, less social
      support at work, less job control, more effort-reward imbalance and higher levels
      of hostility, when adjusting for age and sex. Afro-Caribbeans, compared to
      Whites, had lower minor psychiatric morbidity and lower Type A scores. The
      remaining psychosocial factors showed either no ethnic differences in
      distribution, or differences contrary to those predicted from coronary event
      rates. Adjustment for employment grade made little difference to these
      associations. CONCLUSION: Among South Asians, the majority of whom were Indian,
      the distribution of psychosocial factors was consistent with ethnic differences
      in coronary rates; the pattern for Afro-Caribbeans was less consistent. Further
      research is required to test the extent to which psychosocial factors predict
      coronary events within ethnic groups and to characterize better psychosocial
      measures.

PMID- 11572406
TI  - South Asian people and heart disease: an assessment of the importance of
      socioeconomic position.
AB  - OBJECTIVES: Higher rates of mortality from ischemic heart disease among South
      Asian people are well established and appear to be unrelated to socioeconomic
      position. However, traditional indicators of socioeconomic position may be
      inadequate when making comparisons across ethnic groups. This study investigates
      these issues in a British morbidity survey. METHODS: The Fourth National Survey
      was a British cross-sectional study conducted from 1993 to 1994. The study used a
      national representative community sample, consisting of 2867 white respondents,
      2001 Indian respondents, and 1776 Pakistani and Bangladeshi respondents. Data on
      occupational class and standard of living were used to examine the contribution
      of socioeconomic factors to differences in rates of reported severe chest pain
      and diagnosed heart disease. RESULTS: White and Indian respondents had similar
      rates of reported indicators of heart disease, while Pakistani and Bangladeshi
      respondents had rates that were considerably higher. There was a clear
      socioeconomic gradient in reported heart disease for each ethnic group, with
      those who were poorer having higher rates. Controlling for occupational class
      made little difference to the greater risk of heart disease found in the
      Pakistani and Bangladeshi group; however, controlling for a more sensitive
      indicator of socioeconomic position-standard of living-greatly reduced their
      disproportionate risk. DISCUSSION: The findings suggest that South Asian people
      do not share a uniformly greater risk of heart disease. The more economically
      advantaged South Asian group, Indians, had rates that are similar to those found
      among white people, while the poorest groups, Pakistanis and Bangladeshis, had
      rates that are considerably higher. Socioeconomic position predicted risk in each
      ethnic group and made a key contribution to the higher risk found for Pakistani
      and Bangladeshi individuals. Other studies may have failed to identify the
      important contribution of socioeconomic position because the indicators used were
      too crude.

PMID- 11572407
TI  - High prevalence of hypertension among Black and Mulatto women in a Brazilian
      survey.
AB  - STUDY OBJECTIVES: Brazil has a high admixture of Blacks and Whites, making it
      possible to compare the prevalence of hypertension among Blacks, Whites, and
      Mulattos. DESIGN: A population-based health and nutrition survey was carried out
      in 1996 in the city of Rio de Janeiro, Brazil. Blood pressure, weight, height,
      food frequency information, and skin color were obtained from a sample of 2,802
      private household residents aged 20 years or older. MAIN OUTCOME MEASURE:
      Hypertension was defined as systolic blood pressure >140 mm Hg and/or diastolic
      pressure >90 mm Hg or the use of antihypertensive medication. RESULTS: The
      prevalence of hypertension among men was 12.0% among Whites, 13.8% among
      Mulattos, and 14.4% for Blacks. For women, these prevalences were 12.0%, 16.4%,
      and 20.2%, respectively. After adjustment for age, calcium and salt intake,
      physical activity level, body mass index, and waist-hip ratio, we observed (among
      women only) a trend toward increasing prevalence of hypertension with increasing
      skin darkness. The adjusted odds ratio of hypertension was 1.52 for Mulatto women
      compared to Whites and 2.27 for Blacks compared to Whites (P<.05). With further
      adjustment for income, the odds ratios were reduced to 1.30 (95% CI 0.86-1.95)
      and 1.75 (95% CI 1.04-2.94). CONCLUSIONS: Black women showed increased risk of
      hypertension independent of socioeconomic factors or overweight status.

PMID- 11572408
TI  - Awareness status and prevalence of hypertension in a group of urban Haitians:
      findings of a population-based survey.
AB  - PURPOSE: The primary purpose of this project was to evaluate knowledge and
      awareness status about hypertension among a group of Haitian adults in Port-au
      Prince, Haiti, and also to assess treatment status among hypertensive persons
      within this group. METHODS: Adults (> or =18 yrs) accompanying a sick person to a
      private clinic or a health center were asked to participate in a cross-sectional
      survey. Face-to-face questionnaires were administered to volunteers. Blood
      pressure measurements, weight, and height were obtained on site. RESULTS: A total
      of 382 subjects enrolled. Two hundred and eighty-nine subjects (approximately
      76%) were normotensives. Among hypertensives: thirty-nine (10%) had borderline
      hypertension with systolic pressure > or =140<160 mm Hg and diastolic pressure >
      or =90<95 mm Hg, while fifty-four (14%) had blood pressure levels > or =160/95 mm
      Hg. Among subjects classified as hypertensive, fifty-seven (61%) were unaware of
      their high blood pressure and its risk. Only 3 of those aware (8%) reported
      receiving regular therapy. Thirty percent (30%) of participants believed
      hypertension was not a serious problem. CONCLUSION: These results highlight the
      need for information about awareness, prevalence, and control of hypertension in
      Haiti's population. This information could be used as the baseline in the
      planning of a cost-effective national primary prevention strategy.

PMID- 11572410
TI  - Conducting focus groups for health research among Asian communities: insights and
      experiences.
AB  - An exploratory qualitative study was undertaken in Luton to examine the issues
      that may underlie the severe shortage of organ donors from the United Kingdom's
      (UK) Asian population. To date, this subject area had not been researched within
      this sub-population of the UK. Thus, focus groups were employed as the initial
      stage of research to pre-test the applicability and validity of questions used in
      empirical studies undertaken within other cultural groups, and to allow the
      opportunity for new and unexpected issues to emerge. These focus groups also
      allowed us to gauge the response of conducting research on a sensitive topic
      among the Asian communities in Luton. The processes involved in conducting focus
      group discussions among Asian communities, and in using the subsequent findings
      to inform a semi-structured questionnaire, are discussed.

PMID- 11572409
TI  - The epidemic of obesity in South Africa: a study in a disadvantaged community.
AB  - OBJECTIVE: The objective of this study was: 1) to determine the anthropometric
      profile of adults in Mamre, a small town in South Africa, which has a population
      of mixed ancestry ("colored" people of Afro-Euro-Malay-Khoisan ancestry); and 2)
      to determine the change in this profile between 1989 and 1996. DESIGN: Cross
      sectional surveys conducted in random samples of adults in 1989 and 1996.
      PARTICIPANTS: The subjects were 684 women and 529 men in 1989, and 546 women and
      430 men in 1996, aged 15 and older. MAIN OUTCOME MEASURES: The following
      measurements were recorded: height, weight, and circumference of waist, hips, and
      mid-upper arm. RESULTS: Based on data from the 1996 survey, 32% of women are
      obese (body mass index [BMI] > or = 30) at ages 25-44 years, rising to 49% at
      ages 45-64 years. A much lower prevalence of obesity is seen in men: 14% at ages
      35-64 years. Obesity levels significantly increased in women between the two
      surveys (P=.015): up from 44% in 1989 to 49% in 1996 at ages 45-64 years. There
      was an increase in the prevalence of overweight (BMI 25-29.9) in men, though not
      in obesity. Mean BMI increased by about 3% in women and 2% in men between 1989
      and 1996. CONCLUSIONS: This study conducted among people of mixed ancestry living
      in a disadvantaged community in South Africa shows that half of middle-aged women
      are obese. A rising trend in BMI was seen in adults of both sexes between 1989
      and 1996. This trend may be explained by factors associated with rural-urban
      transition, including electrification, reduced physical activity, and increasing
      availability of energy-dense food.

PMID- 11572411
TI  - Resting ECG abnormalities among asymptomatic Arab men and comparison with other
      ethnic populations.
AB  - The aim of this study was to detect the frequency of the resting
      electrocardiogram (ECG) abnormalities among asymptomatic Arab men in Saudi
      Arabia, since no similar studies had been conducted in this ethnic population.
      The ECG tracings of 314 men (mean age 44.2 years) who attended a health clinic in
      Abha, Southern Saudi Arabia, were analyzed according to the definitions of the
      major ECG textbooks and the Minnesota code. Abnormal ECG findings were
      encountered in 99 men (31.5%); 39 (12.4%) had non-specific changes, while 60
      (19.1%) had potentiallysignificantabnormalities. Serious abnormalities, such as
      ischemic changes, left ventricular hypertrophy, and atrial fibrillation were seen
      in only 22 subjects (7%) and were associated with hypertension and an age greater
      than 40 years. On the other hand, early repolarization, the most frequent
      abnormality encountered, and Wolf-Parkinson-White syndrome (WPW) were mostly
      prevalent among young subjects. The significance of these ECG abnormalities with
      regard to long-term morbidity and mortality in asymptomatic subjects should be
      considered in relation to the age of the person and the presence of any
      underlying cardiovascular disease.

PMID- 11572412
TI  - Lack of adequate attention to elevated blood pressure in an urban hypertensive
      population.
AB  - BACKGROUND: Efforts directed at improving blood pressure (BP) control and
      outcomes of hypertension require insight into how physicians diagnose and manage
      hypertension in various practice settings, especially in the non-continuity
      setting. METHODS: Retrospective, cross-sectional study. Chart review of records
      of hypertensive patients, and patients with elevated BP, who visited the Urgent
      Care Center (UCC) of an urban teaching hospital. We examined patients'
      characteristics associated with the diagnosis and treatment of hypertension.
      RESULTS: Complaint of hypertension, request for medication refill, history of
      hypertension and high stages of hypertension, were associated with attention to
      BP. Complaint of hypertension and request for medication refill were associated
      with prescription for antihypertensive medications. Eighty percent of stage I,
      50% of stage II, and 30% of stage III levels of BP did not have their BP
      addressed. Attention to the blood pressure reading was significantly associated
      with referral for follow-up care. CONCLUSIONS: Providers do not adequately
      acknowledge elevated BP in the UCC. Progress in the fight against hypertension
      will require a change in the practice of hypertension care in the non-continuity
      setting to recognize elevated blood pressures during patient encounters.

PMID- 11572413
TI  - Association of atypical chest pain presentations by African Americans and the
      lack of utilization of reperfusion therapy.
AB  - OBJECTIVE: One possible factor resulting in delays in using reperfusion therapy
      in patients with acute myocardial infarction (AMI) is the failure to recognize
      cardiac symptomatology early in certain subgroups of patients. These patients may
      undergo extensive evaluation for gastrointestinal or musculoskeletal complaints
      before it is recognized that they are suffering from an AMI. METHODS: The records
      of patients (52% Black and 48% White; 49% male and 51% female) presenting to an
      urban teaching hospital with enzyme documented myocardial infarctions were
      retrospectively examined for traditional elements of atypia in their initial
      chest pain descriptions to the emergency department (ED). The rate of reperfusion
      therapy utilization was also determined for this group. RESULTS: Of the patients
      meeting the study criteria (166 total), 43% were found to have atypical elements
      in the character of their pain description. This high prevalence of atypia also
      coincided with a low reperfusion intervention rate of 38%. In examining the
      subgroups, it appears that African Americans and women had the highest rates of
      atypical pain (56% and 46%, respectively) while also having the lowest
      utilization rates for reperfusion therapies (31% and 33%, respectively). This
      compares to rates of 48% for Whites and 60% for White males who had more typical
      chest pain. CONCLUSIONS: While no direct correlation can be drawn from the data,
      it has been suggested that atypical presentations may result in early failure to
      recognize myocardial infarction and cause delay in or prevent appropriate
      therapy. It is thought that chest pain should be de-emphasized as a part of the
      indication criteria for thrombolytics and emergent angioplasty.

PMID- 11572414
TI  - Widening Black/White mortality differentials among US children during the 1980s.
AB  - OBJECTIVES: With the exception of infants, mortality rate differentials among
      Black and White children have received very little attention. We address four
      empirical questions: 1) Did the Black/White childhood mortality disparity grow
      between 1980 and 1990? 2) What causes of death account for Black/White
      disparities in childhood mortality and temporal changes in the size of this
      disparity? 3) Do economic disparities between Black and White families account
      for Black/White childhood mortality differentials in 1980 or 1990? 4) Do growing
      economic disparities between Black and White families explain any growth in
      childhood mortality differentials? METHODS: Childhood mortality patterns and
      causes of excess deaths in Black children are examined in the nation overall and
      in three major metropolitan areas-Chicago, Detroit, and New York-using a dataset
      combining death certificate and Census data. Logistic regression analyses utilize
      Census socioeconomic information to identify the relationship between mortality
      risk and local area income in the metro areas. RESULTS: Black children's relative
      mortality disadvantage grew more severe during the 1980s, with startling growth
      in Black/White disparities seen in many age- and sex-specific metro populations.
      While White children generally experienced marked mortality declines, Black
      children's rates fell more slowly or actually increased, most dramatically among
      adolescent boys in Detroit and Chicago. Excess deaths among younger Black
      children were most often fire-related, while homicide was the predominant cause
      at older ages. Regression analyses confirmed that areal income was significantly
      and strongly related to child mortality at both time points in all study areas.
      However, the deterioration in areal income for Black children relative to Whites
      from 1980 to 1990 did not explain their worsening mortality rates over the time
      period. CONCLUSIONS: Black children are increasingly suffering excess deaths
      relative to White children. We find that Black children's mortality disadvantage
      is largely accounted for by areal economic disadvantage; however, expanding death
      rate disparities over time represented more than simply growth in income
      differentials. Our results suggest that other adverse exposures also have
      increasingly served to compromise Black children's life chances during the 1980s.

PMID- 11572415
TI  - Psychosocial stress and prostate cancer: a theoretical model.
AB  - African-American men are more likely to develop and die from prostate cancer than
      are European-American men; yet, factors responsible for the racial disparity in
      incidence and mortality have not been elucidated. Socioeconomic disadvantage is
      more prevalent among African-American than among European-American men.
      Socioeconomic disadvantage can lead to psychosocial stress and may be linked to
      negative lifestyle behaviors. Regardless of socioeconomic position, African
      American men routinely experience racism-induced stress. We propose a theoretical
      framework for an association between psychosocial stress and prostate cancer.
      Within the context of history and culture, we further propose that psychosocial
      stress may partially explain the variable incidence of prostate cancer between
      these diverse groups. Psychosocial stress may negatively impact the immune system
      leaving the individual susceptible to malignancies. Behavioral responses to
      psychosocial stress are amenable to change. If psychosocial stress is found to
      negatively impact prostate cancer risk, interventions may be designed to modify
      reactions to environmental demands.

PMID- 11572416
TI  - Understanding the Hispanic paradox.
AB  - PURPOSE: This paper reviews the literature on the nature of the Hispanic paradox
      and the major explanations provided for it. We conclude by suggesting directions
      for future research. DATA IDENTIFICATION AND STUDY SELECTION: Articles were
      selected by a systematic review procedure using Medline (1966 through 1999) and
      Sociological Abstracts (1963 through 1999), as well as focused searches on
      specific diseases or factors believed to influence Hispanic health. FINDINGS: For
      the past twenty years there has been widespread evidence of an Hispanic paradox
      in the United States, in which most Hispanic groups are characterized by low
      socioeconomic status, but better than expected health and mortality outcomes. A
      closer look reveals variations by age, gender, Hispanic subgroup, acculturation,
      country of birth, and cause of death. Possible under-reporting of Hispanic
      deaths, "salmon bias" and healthy migrant effects, and risk profile may
      contribute to, but do not explain, the paradox. The reasons for this paradox are
      likely to be multifactorial and social in origin. CONCLUSIONS: Empirical studies
      should be conducted on the protective effects of immigrant status, identification
      with a subculture, interaction between acculturation and socioeconomic status,
      and supportive aspects of Hispanic culture.

PMID- 11572417
TI  - The impact of population admixture on traditional linkage analysis.
AB  - INTRODUCTION: Families of admixed ancestry are routinely excluded from
      traditional (Log of the Odds [LOD] score) linkage analysis or are analyzed as
      being derived from a homogeneous population using the proband's ethnicity. Using
      traditional linkage analysis with these families can cause complications due to
      the mixing of different disease rates and allele frequencies that occurs. The
      presence of admixture violates the key assumptions of Hardy-Weinberg Equilibrium
      (HWE) and Linkage Equilibrium (LE) invoked in the current methods of linkage
      analysis. If one or more of these assumptions are violated, incorrect inference
      for linkage could result. DESIGN AND METHODS: Through simulation, we investigated
      the effect of admixture of two populations on the LOD score under various
      conditions, using prostate cancer as our underlying disease model. Four
      generation homogeneous and admixed families were simulated with 27 markers and
      two linked, bi-allelic disease loci. Two different types of admixture were
      tested: admixture within a family unit and a mixture of homogeneous families
      within a data set. All mixing was done at the founder level in three different
      proportions: 30/70, 50/50 and 70/30. RESULTS AND CONCLUSIONS: We observed that
      the LOD scores under both models of admixture were closest to the homogeneous
      family scores of the population having the highest mixing proportion. Random
      sampling of families or ascertainment of families with disease affection status
      did not affect this observation, nor did the mode of inheritance
      (dominant/recessive) or sample size. Thus, the presence of families of mixed
      population ancestry impacts linkage analysis in terms of the LOD score and the
      estimate of the recombination fraction.

PMID- 11572418
TI  - Smoking in urban African Americans: behaviors, gender differences, and motivation
      to quit.
AB  - OBJECTIVE: This study describes smoking behaviors and gender differences, and
      correlates these factors with motivation to quit smoking among African-American
      smokers at a community-based health center. DESIGN: A 62-item survey assessed
      depression, hassles, readiness to change, and demographics. METHODS: Participants
      (N = 81) were interviewed in an adult clinic waiting room. RESULTS: On average,
      participants smoked 13 cigarettes per day. Many reported attempts to reduce
      smoking-related health risks: 46% switched brands, 57% reduced their smoking, and
      19% smoked only on some days. Fifty-nine percent indicated depressive symptoms.
      For women vs men, noteworthy differences were: reduction in number of cigarettes
      smoked (66.7% vs 40.0%; P = .023), switching brands (58.8% vs 23.3%; P = .003),
      number of attempts to quit in the past year (2.7 vs 1.2; P = .034), and high
      concern about weight gain (52.9% vs 26.7%; P = .047). Cigarettes smoked per day
      was negatively correlated with motivation to quit (P = .022). Variables
      positively correlated with motivation to quit included: harm reduction strategies
      (P = .002), intention to quit in 30 days (P<.0001), and intention to quit in 6
      months (P<.0001). CONCLUSIONS: Women showed more potential indications of
      readiness to quit, including more attempts to quit, reductions in number of
      cigarette smoked, and brand switching. Knowledge of cessation barriers, gender
      differences, and correlates to motivation may prove useful for investigators
      conducting research in this population.

PMID- 11572419
TI  - Smoking in Maywood: the unhealthy southern migrant hypothesis among African
      Americans.
AB  - OBJECTIVES: This paper examines the "unhealthy Southern migrant" hypothesis with
      regard to cigarette smoking among African Americans. METHODS: Using data
      collected in 1992 from a sample of 1,518 African Americans in Maywood, Illinois,
      as part of the International Collaborative Study of Hypertension in Blacks,
      logistic regression analysis was conducted to examine and compare smoking
      behavior and sociodemographic characteristics of Southern and Midwestern-born
      respondents. RESULTS: African Americans born in the South were less likely (OR =
      .69, CI = 95%, 0.53, 0.90) to be smokers than those born in the Midwest, after
      controlling for other sociodemographic variables, prior smoking status, and age
      of arrival to Maywood. CONCLUSIONS: The results do not support the "unhealthy
      Southern migrant" hypothesis, with regard to cigarette smoking, and indicate the
      need to identify factors that protect Southern-born African-American migrants
      from smoking.

PMID- 11572420
TI  - Compliance with hepatitis B virus vaccination in a high-risk population.
AB  - OBJECTIVE: To quantify cultural barriers to hepatitis B virus (HBV) vaccination
      and parental compliance with a specific vaccination protocol among a primarily
      among population of infants born at a community hospital. METHODS: This study was
      concurrent with an immunogenicity study of two vaccination schedules and occurred
      prior to the inception of universal infant vaccination with hepatitis B vaccine
      (HepB). In this study, parental pairs were interviewed, consent obtained,
      subjects were randomly assigned to each group, and first immunization was
      administered in the hospital. Follow-up contacts required for completion were
      documented. RESULTS: Of 260 eligible parental pairs interviewed, 175 (67%)
      declined participation, mainly because of fears of vaccine side effects (55%) or
      ignorance of the hepatitis B virus (HBV) (30%). Of 85 infants enrolled in the
      study, 28 (33%) were later withdrawn from the study; 13 (46%) of these 28 infants
      were withdrawn at the request of parents. Each infant who completed the study
      received 5 postcards, 10 phone calls, and 3 home visits. CONCLUSIONS: Families
      were unaware of the risk of HBV infection and feared vaccination. Aversion to
      subjecting an infant to pain was a principal reason for failure to complete the
      study, and frequent contacts were required to ensure adherence. Existence of a
      safe and effective hepatitis B vaccine and universal vaccination is unlikely to
      change deeply felt attitudes against vaccination. Current vaccination strategies
      must take these prejudices into account.

PMID- 11572421
TI  - Perceived race-based and socioeconomic status(SES)-based discrimination in
      interactions with health care providers.
AB  - OBJECTIVE: The purpose of this study was to: 1) examine whether African Americans
      perceive race-based and socioeconomic status(SES)-based discrimination in their
      interactions with health care providers; 2) explore the relationship between
      perceived discrimination and health care utilization; and 3) examine the
      interrelationships among education, stigma consciousness, and perceived
      discrimination. DESIGN: Cross-sectional. METHODS: Seventy-six African-American
      adults (59 women and 17 men) completed self-report questionnaires regarding their
      experiences with and attitudes toward health care providers. RESULTS: Almost two
      thirds (63%) of participants perceived discrimination in their interactions with
      health care providers based on their race or color, and 58.9% perceived
      discrimination based on their socioeconomic status or social class. Some
      experiences of perceived discrimination were correlated with measures of health
      care utilization. Education and stigma consciousness were positively correlated
      with perceptions of both race-based and SES-based discrimination. Stigma
      consciousness was not significantly correlated with education, suggesting that
      expectations that one will be stereotyped by doctors do not account for the
      relationship between education and reports of perceived discrimination in
      interactions with health care providers. CONCLUSION: Further research is needed
      to assess the prevalence, frequency, and consequences of perceived discrimination
      in health care interactions.

PMID- 11572422
TI  - The changing character of regulation: a comparison of Europe and the United
      States.
AB  - European and U.S. regulatory policies have changed considerably over the past 30
      years. In Europe, since the mid-1980s, consumer and environmental regulation has
      become more politically salient and regulations have by and large become
      stricter. On the other hand, in the United States consumer and environmental
      issues have become less salient and contentious, and regulations have not become
      (comparatively) stricter. This apparent "flip-flop" of regulatory systems has not
      been analyzed in much detail to date. This perspective is an attempt to analyze
      some examples in which it has occurred and identifies one possible cause--namely,
      credibility.

PMID- 11572423
TI  - Advancing environmental risk education.
AB  - This article summarizes views on environmental risk education for youth and
      identifies some challenges to advancing environmental risk education. It is
      argued that education--in particular, formal (in-school, structured) education-
      can play an important role in helping to create an environmental risk-literate
      society. Recommendations focus on developing a framework of environmental risk
      education goals and objectives, evaluating environmental risk education efforts,
      and learning more about how to help youth make informed environmental risk
      decisions and to prepare them to participate in environmental risk management. It
      is hoped that this article will encourage greater involvement of risk
      professionals in environmental risk education efforts and related research.

PMID- 11572424
TI  - Information technology risks as seen by the public.
AB  - Risks related to information technology (IT) are becoming a focus of concern in
      current risk debates. The use of IT is rapidly spreading in the population, as is
      access to computers in general. The present article reviews the literature on IT
      use (especially electronic mail and various Internet applications) and the
      related risks. In addition, the results from a survey about IT use and risk
      perception, given to a random sample of the Swedish population, are reported. In
      general, participants were quite positive to IT and were, to some extent, aware
      of the related risks. However, risks of IT were mostly seen as pertinent to other
      people, a finding in contrast with other results on perceived technology hazards.
      The attitude toward the use of IT was strongly related to general attitude toward
      computers, and less clearly to risk perception. Only a small percentage of the
      respondents reported having had negative experiences with IT hazards such as
      Internet addiction, depression, and social isolation. When extrapolated to the
      general population, however, these small percentages amount to large groups in
      the population that have been negatively affected by IT use.

PMID- 11572425
TI  - Analytical paradigms: the epistemological distances between scientists, policy
      makers, and the public.
AB  - The effective use of evidence and its resultant knowledge is increasingly
      recognized as critical in risk analysis. This, in turn, has led to a growing
      concern over issues of epistemology in risk communication, and, in particular,
      interest in how knowledge is constructed and employed by the key players in risk-
      scientists, policy makers, and the public. This article uses a critical
      theoretical approach to explore how evidence is recognized and validated, and how
      limits are placed on knowledge by scientists, policy makers, and the public. It
      brings together developments in the sociology of science, policy and policy
      development, public understandings of science, and risk communication and
      analysis to explicate the differing forms of rationality employed by each group.
      The work concludes that each group employs different, although equally
      legitimate, forms of rationality when evaluating evidence and generating
      knowledge around risky environment and health issues. Scientists, policy makers,
      and the public employ scientific, political, and social rationality,
      respectively. These differing forms of rationality reflect underlying
      epistemological distances from which can develop considerable misunderstandings
      and misinterpretations.

PMID- 11572426
TI  - Personality correlates of risk perception.
AB  - The aim of the present study was to systematically examine the variations of the
      effects of (1) transitional anxiety states and enduring anxiety dispositions, and
      (2) worldviews (hierarchic, egalitarian, individualist, and fatalist), as a
      function of the type of hazard considered. Ten risk factors were identified.
      Transitional anxiety contributed significantly to the prediction of four of these
      risk factors. The more anxious the respondents, the higher were their scores for
      the Common Individual Hazards, Pollutants, and Outdoor Activities factors, and
      the lower were their scores for the Public Transportation and Energy Production
      factor. Enduring anxiety contributed significantly to the prediction of the
      Psychotropic Drugs factor. The more anxious the respondents, the lower were their
      scores. The four worldview factors contributed significantly to the prediction of
      three of these risk factors. The more fatalistic the respondents, the lower were
      their scores for the Pollutants factor, and the higher were their scores for the
      Public Transportation and Energy Production factor; the more egalitarian the
      respondents, the higher were their scores for the Pollutants factor; the more
      hierarchic the respondents, the lower were their scores for the Public
      Transportation and Energy Production factor; and the more individualistic the
      respondents, the higher were their scores for the Pollutants and Deviance, Sex,
      and Addiction factors.

PMID- 11572427
TI  - Source credibility in environmental health-risk controversies: application of
      Meyer's credibility index.
AB  - This article applies an existing five-item index for measuring source credibility
      in the context of environmental health-risk controversy. Survey data were
      gathered in five upstate New York communities facing environmental health-risk
      issues. Analysis of the five case studies and a combined dataset (N = 870) show
      that the credibility index was consistently reliable across all applications. Use
      of the resulting index is demonstrated through a comparison of the credibility of
      the New York State Department of Health (active in each case), the industries
      associated with each case, and the newspaper providing coverage of each case. The
      credibility index was used to predict risk judgments in a structural equation
      model. Overall, the analysis demonstrated that the credibility index performed
      consistently well across the five cases and illuminated important differences in
      each. As such, the index should be a useful addition to many environmental health
      and risk communication studies.

PMID- 11572428
TI  - Scenario-based risk assessment of multi-use chemicals: application to solvents.
AB  - The risk through chemical exposure is commonly characterized by ratios of
      exposure concentrations and effect levels (risk quotients). For chemicals with
      many different applications such as solvents, however, in addition to the risk
      quotients of different exposure situations it is useful to determine the
      corresponding numbers of exposed individuals, that is, not only the magnitude but
      also the extent of the risk. To this end, the Scenario-Based Risk Assessment
      (SceBRA) method has been developed that makes use of a large set of scenarios,
      each of which describes a typical situation regarding handling a solvent or
      solvent-containing product. The scenarios cover the life-cycle steps of
      production, distribution, and use of solvents. For each scenario, SceBRA provides
      the risk quotient, r, and the number of exposed individuals, N. This study
      investigated seven solvents that are used in large amounts in Switzerland. For
      each solvent, characteristic distributions of r and N values were calculated,
      making it possible to compare different solvents with respect to their risk
      profile. Graphical representations of the r, N data provide an informative way
      for analyzing and communicating the results of SceBRA.

PMID- 11572429
TI  - Variation of consumer contact with household products: a preliminary
      investigation.
AB  - Little information is available on product use by consumers, which severely
      hampers exposure estimation for consumer products. This article describes actual
      contact with several consumer products, specifically dishwashing detergents,
      cleaning products, and hair styling products. How and where products are handled,
      as well as the duration, frequency, and amount of use were studied by means of
      diaries, in-home observations, and measurements. This study addressed the
      question, "To what extent are frequency, duration, and amount of use associated?"
      Findings showed that there was a large intra- as well as interindividual
      variation in frequency, duration, and amount of use, with the interindividual
      variation being considerably larger. At the same time, results showed that, for a
      given activity, users tended to follow their own routine. Few relations were
      found among frequency, duration, and amount of use. It was concluded that among
      persons, frequency, duration, and amount of product act in practice as
      independent parameters. Diaries appear to be quite suitable for gaining insight
      into frequently used products. Observations of usage, recorded on video, were
      indispensable for obtaining particular information on product use. In addition,
      home visits enabled the collection of specific measurements. Although diaries and
      home visits are time-consuming, the combination provided insight into variation
      as well as relations among frequency, duration, and amount of use.

PMID- 11572430
TI  - The chemical accident risk assessment thesaurus: a tool for analyzing and
      comparing diverse risk assessment processes and definitions.
AB  - The Chemical Accident Risk Assessment Thesaurus (CARAT) is a database of the
      laws, regulations, guidance documents, and definitions of terms related to the
      risk assessment of accidental releases of chemicals from fixed installations. The
      database also contains information on the application of risk assessment
      methodologies to specific examples of potential chemical releases. The
      Organization for Economic Cooperation and Development urged the development of
      the Thesaurus to improve the communication among the member countries about the
      risk assessment of hazardous installations. The difficulty of communication is
      based in large part on the fact that certain "terms of art" have different
      meanings in different countries and cultures, or that different terms of art are
      used to address the same concept. The CARAT is designed to circumvent these
      difficulties, and is especially useful as a tool to analyze the definitions of
      terms related to risk assessment. Entries into the CARAT contain information from
      various international, national, and regional agencies that relate to risk
      assessment processes and definitions focused on accidental chemical releases. The
      entire system is accessible via the Internet. Retrieval of information from the
      CARAT is facilitated by five different searching tools: two of them are designed
      to search the CARAT for its entries. One facility is designed to search for laws
      and regulations, specific risk assessment cases (SRA), and risk assessment
      guidance documents (RAG) related to chemical accidents. The second search
      facility deals with entries of definitions. The design of the CARAT is ideally
      suited to capture the sense of definitions that are expressed as either a
      procedural definition (an "operation on a concept") or a conceptual definitions
      (just the "concept"). A powerful third query tool is the "Comparison" facility.
      This query tool allows the user to compare the details CARAT entries of laws and
      regulations, SRA, RAG, or definitions, in any combination. The remaining two
      tools can perform searches by identifying entries that contain either certain
      combinations of hierarchical or descriptor details. Both types can be conducted
      in Boolean "and/or" mode.

PMID- 11572431
TI  - Ethnic differences in risk from mercury among Savannah River fishermen.
AB  - Fishing plays an important role in people's lives and contaminant levels in fish
      are a public health concern. Many states have issued consumption advisories;
      South Carolina and Georgia have issued them for the Savannah River based on
      mercury and radionuclide levels. This study examined ethnic differences in risk
      from mercury exposure among people consuming fish from the Savannah River, based
      on site-specific consumption patterns and analysis of mercury in fish. Among
      fish, there were significant interspecies differences in mercury levels, and
      there were ethnic differences in consumption patterns. Two methods of examining
      risk are presented: (1) Hazard Index (HI), and (2) estimates of how much and how
      often people of different body mass can consume different species of fish. Blacks
      consumed more fish and had higher HIs than Whites. Even at the median
      consumption, the HI for Blacks exceeded 1.0 for bass and bowfin, and, at the 75th
      percentile of consumption, the HI exceeded 1.0 for almost all species. At the
      White male median consumption, noHI exceeded 1, but for the 95th percentile
      consumer, the HI exceeded 1.0 almost regardless of which species were eaten.
      Although females consumed about two thirds the quantity of males, HIs exceeded 1
      for most Black females and for White females at or above the 75th percentile of
      consumption. Thus, close to half of the Black fishermen were eating enough
      Savannah River fish to exceed HI = 1. Caution must be used in evaluating an HI
      because the RfDs were developed to protect the most vulnerable individuals. The
      percentage of each fish species tested that exceeded the maximum permitted limits
      of mercury in fish was also examined. Over 80% of bowfin, 38% of bass, and 21% of
      pickerel sampled exceeded 0.5 ppm. The risk methodology is applicable anywhere
      that comparable data can be obtained. The risk estimates are representative for
      fishermen along the Savannah River, and are not necessarily for the general
      populations.

PMID- 11572432
TI  - Radiocesium in fish from the Savannah River and Steel Creek: potential food chain
      exposure to the public.
AB  - This study examined radiocesium (137Cs) levels in fish from the vicinity of the
      Department of Energy's Savannah River Site (SRS), a former nuclear weapons
      production facility in South Carolina. Fish from the Savannah River were sampled
      above (upstream), along, and below (downstream) the SRS, and from Steel Creek, a
      tributary that runs through the SRS. There was some off-site contamination of
      137Cs in the Savannah River watershed due to low-level releases from past nuclear
      production on the SRS. The null hypotheses tested were that there would be no
      differences in 137Cs levels as a function of location along the river, and
      between species collected from the river and from Steel Creek on the SRS. For six
      of eight species of fish collected from the Savannah River, there were no
      differences in 137Cs levels in muscle from fish collected above, along, or below
      the SRS; exceptions were bowfin and shellcracker. Fish collected from Steel Creek
      had significantly higher levels (by about an order of magnitude) of 137Cs in
      muscle tissue than fish collected in the Savannah River. However, no fish from
      either Steel Creek or the Savannah River had 137Cs levels above the European
      Economic Community limit for fresh meat of 0.6 Bq/g. Lifetime cancer risk was
      calculated using the cancer slope factor of 3.2 x 10(-11)/pCi, and various fish
      consumption scenarios reflecting actual data from Savannah River fishermen. Using
      mean 137Cs concentrations and median fish consumption for 70 years for Black
      males-the group with the highest consumption-the excess lifetime risk associated
      with the eight species of fish in the Savannah River ranged from 9.0 x 10(-7) to
      1.0 x 10(-5). The same calculation for fish from Steel Creek gave risk estimates
      from 1.4 to 8.0 x 10(-5). The 95% level for consumption by Blacks, however, was
      about 70 kg/year. Black fishermen consuming that amount of bass from Steel Creek
      would sustain a lifetime risk of 3.1 x 10(-4), whereas the same consumption of
      Savannah River bass would yield a risk estimate of 1.5 x 10(-5).

PMID- 11572433
TI  - An exploratory study of variations in exposure to environmental tobacco smoke in
      the United States.
AB  - There is considerable interest in assessing exposure to environmental tobacco
      smoke (ETS) and in understanding the factors that affect exposure at various
      venues. The impact of these complex factors can be researched only if monitoring
      studies are carefully designed. Prior work by Jenkins et al. gathered personal
      monitor and diary data from 1,564 nonsmokers in 16 metropolitan areas of the
      United States and compared workplace exposures to ETS with exposures away from
      work. In this study, these data were probed further to examine (1) the
      correspondence between work and away-from-work exposure concentrations of ETS;
      (2) the variability in exposure concentration levels across cities; and (3) the
      association of ETS exposure concentrations with select socioeconomic, occupation,
      and lifestyle variables. The results indicate (1) at the population level, there
      was a positive association between ETS concentrations at the work and away-from
      work environments; (2) exposure concentration levels across the 16 cities under
      consideration were highly variable; and (3) exposure concentration levels were
      significantly associated with occupation, education, household income, age, and
      dietary factors. Workplace smoking restrictions were associated with low ETS
      concentration levels at work as well as away from work. Generally, the same
      cities that exhibited either lower or higher away-from-work exposure
      concentration levels also showed lower or higher work exposure concentration
      levels. The observations suggest that similar avoidance characteristics as well
      as socioeconomic and other lifestyle factors that affect exposure to ETS may have
      been in operation in both away-from-work and work settings.

PMID- 11572434
TI  - Improvement on in vitro maturation, fertilization and development of minke whale
      (Balaenoptera acutorostrata) oocytes.
AB  - The aims of the present study were to improve in vitro maturation, fertilization
      and subsequent development of minke whale oocytes. We investigated the effects of
      different concentrations (0, 10 and 20%) of fetal whale serum (FWS) in maturation
      medium on nuclear maturation, morphological grade (A or B) of cumulus-oocyte
      complexes (COC) obtained from prepubertal and adult minke whales. Grade A (> or =
      5 layers of cumulus cells) COC collected from the adult whales and cultured in
      the medium with 20% FWS had a higher (P < 0.05) maturation rate (31.8%) than
      those in the medium without FWS (0%). Adding FWS to the maturation medium
      significantly (P < 0.01) improved the proportion of oocytes at Metaphase II (M
      II): without FWS (7.9%), with 10% (19.4%) and 20% (21.4%) FWS. However, sexual
      maturity of whales and COC grades were not significantly affected by M-II
      oocytes. When in vitro fertilization of matured oocytes was performed in the
      presence of 20% FWS or 0.6% BSA in the fertilization medium, the proportions of
      sperm penetration and two-pronuclei formation in matured oocytes were not
      significantly different. Grade A COC cultured in a culture medium supplemented
      with 10% FWS cleaved at a higher rate (15.4%, P < 0.05) than did Grade A and B
      COCs cultured in the medium without FWS (0%). Neither Grade A nor B COCs cleaved
      when the medium was without FWS. The proportions of cleaved oocytes increased (P
      < 0.05) with FWS supplementation (6.9% and 8.1% for 1.0% FWS and 20% FWS,
      respectively). Grade A COC was significantly (P < 0.05) superior in its ability
      to cleave (14.5%) and develop to morula (4.2%) compared with that of the oocytes
      from Grade B COC (2.5% and 0%). Coculture with granulosa cells during in vitro
      culture did not significantly affect cleavage and development to the morula
      stage. These results indicate that FWS addition in the maturation medium improved
      the rate of in vitro maturation and cleavage after insemination of minke whale
      oocytes. The BSA supplementation in fertilization medium was as effective as FWS
      supplementation for in vitro fertilization of matured oocytes. In vitro embryo
      production beyond the morula stage of minke whale oocytes could be possible, if
      Grade A COC was selected and cultured in the maturation medium supplemented with
      10% or 20% FWS.

PMID- 11572435
TI  - Do sire-dam interactions contribute significantly to fertility comparisons in
      heterospermic insemination trials.
AB  - The percentage of offspring sired after heterospermic insemination of equal
      numbers of spermatozoa is believed to be a very sensitive measure of relative in
      vivo fertility of the inseminated samples. The objective of these trials was to
      evaluate whether there was a detectable male-female interaction in the
      fertilizing ability of spermatozoa. If there was such an interaction, we reasoned
      that the paternity of offspring from individual females in a heterospermic trial
      the second year would be similar to the paternity of offspring in the same
      individual females the first year if the same ejaculates were used. Five groups
      of ewes were inseminated with different combinations of semen (a single Merino
      ejaculate from one of five rams randomly paired with five different pools of
      Suffolk semen) in a heterospermic trial. Those ewes conceiving the first year
      were inseminated in a second breeding season with the same combination of semen
      used previously. The percentage of lambs sired by each ejaculate/pool of
      ejaculates was calculated for all lambs born from all ewes inseminated with each
      semen combination. These percentages would be the expected ratios of Merino
      sired:Suffolk-sired lambs if there is no male-female interaction. Ewes in each
      group were divided into two subgroups: those conceiving only Merino-sired lambs
      the first year and those conceiving at least one Suffolk-sired lamb the first
      year. The ratio of Merino-sired lambs:Suffolk-sired lambs did not differ in
      either subgroup from those expected if there was no male-female interaction.
      These results are consistent with the absence of a male-female interaction in
      relative fertilizing ability of spermatozoa.

PMID- 11572436
TI  - Selection of in vitro produced, transgenic embryos by nested PCR for efficient
      production of transgenic goats.
AB  - The production of valuable pharmaceutical proteins using transgenic animals as
      bioreactors has become one of the goals of biotechnology. However, the efficiency
      of producing transgenic animals by means of pronuclear microinjection is low.
      This may be attributed in part to the low integration rate of foreign DNA.
      Therefore, a large number of recipients are required to produce transgenic
      animals. We recently developed a transgenic procedure that combined the
      techniques of goat oocyte in vitro maturation (IVM), in vitro fertilization
      (IVF), microinjection, preimplantation selection of the transgenic embryos with
      nested PCR and transferring the transgenic embryos into the recipient goat uterus
      to produce transgenic goats. Thirty-seven transgenic embryos determined by nested
      PCR were transferred to thirty-two recipient goats. In the end, four live-born
      kids were produced. As predicted, all the live kids were transgenic as identified
      by PCR as well as Southern blot hybridization, The integration rate was 100%
      (4/4) which was completely in accordance with the results of embryo
      preimplantation detection. The results showed a significant decrease in the
      number of recipients required as only 8 recipients (32/4) were needed to obtain
      one live transgenic goat. We suggest that the transgenic system described herein
      may provide an improved way to efficiently produce transgenic goats on a large
      scale.

PMID- 11572437
TI  - Sperm chromatin structure assay of bulls qualified for artificial insemination.
AB  - The goal of our study was to find the relationship between fertility of bulls
      qualified for AI and the percentage of spermatozoa with abnormal chromatin
      structure as an independent parameter. We used the frozen semen of 8 mature bulls
      from one AI center. Each bull was represented by 3 ejaculates collected with at
      least 2-week intervals. Bull fertility was calculated on the basis of non-return
      ratio and was expressed as a scale where 100 points represented the average
      fertility of all the AI center's bulls. Bulls with lower or higher fertility
      received a lower or higher score respectively. Fertility scores of bulls used in
      the study ranged from 83 to 104 . Semen was processed according to the SCSA
      (sperm chromatin structure assay) method and was analyzed by flow cytometry.
      "Artificial" alpha(t) (alpha(t)=red/green+red fluorescence) and red fluorescence
      histograms were used for calculation of COMPalpha(t), SDalpha(t), %Red, %PeakR
      and MeanR parameters. The percentage of spermatozoa with abnormal chromatin
      ranged from 1.2% to 23.8%. A large variation among ejaculates was found for bulls
      with lower fertility. Fertility correlated significantly with COMPalpha(t) (
      0.50, P < 0.05), SDalpha(t) (-0.55, P < 0.01), %Red (-0.53, P < 0.01), %PeakR (
      0.58, P < 0.01) and MeanR (-0.45, P < 0.05). The SCSA method has a practical
      application in analyzing spermatogenesis disorders in bulls. If regularly
      applied, it allows us to identify and eliminate ejaculates with a high level of
      sperm chromatin abnormalities.

PMID- 11572438
TI  - Morphological and functional characteristics of the dominant follicle and corpus
      luteum in cattle and their influence on ovarian function.
AB  - Predicting the functional activity of a dominant follicle (DF) and corpus luteum
      (CL) might be important before starting a superovulation regime or a
      synchronization program. The DF and CL were characterized morphologically by
      using ultrasonography and were characterized functionally by estimating the
      estradiol-17beta/progesterone (E2/P4) ratio. Their influence on ovarian function
      was estimated through their ability to ovulate at different stages of development
      in response to PGF2alpha-application. A total of 47 Holstein Friesian (35 cows
      and 12 heifers) were used in two experiments. In Experiment 1, 25 animals were
      examined by daily transrectal palpation and ultrasonography to follow the
      morphological development of the DF. The status of the DF was categorized into 3
      groups (A1, B1, C1). The A1 group (n=7) contained animals with DF in the growing
      phase or in early static growth phase for less than 3 days. Group B1 (n=13)
      included animals with DF in static growth phase for 3 to 4 days, while Group C1
      (n=5) comprised animals with DF keeping a plateau for more than 4 days or animals
      with DF in the regression phase. The DF were aspirated transvaginally and the
      follicular fluid (FF) was analyzed for E2 and P4. In Experiment 2, 22 animals
      were included. As in Experiment 1, the animals were classified into three groups
      (A2, n=10; B2, n=5; C2, n=7). They were treated by a single dose of PGF2alpha (25
      mg, i.m.) between Days 8 and 12 of the cycle. Results showed that luteolyses
      occurred in all animals. The DF, which were in growing or in early static growth
      phase < 3 days were always E2-dominant (E2 > P4) and ovulated after PGF2alpha
      application in 6/8 of cases and persisted in 2 (Group A2). The DF persisting > 4
      days or that had been in regression were always P4-dominant. This type of DF
      regressed after PGF2alpha-application (Group C2). The DF in early static growth
      phase for 3 to 4 days in 5/13 cases were E2-dominant and in 8/13 cases were P4
      dominant. This type of DF ovulated in 3/5 cases and regressed in 2/5 cases after
      PGF2alpha-application (Group B2). These results suggest that the DF is
      morphologically and functionally defined as long as the DF is in the growing or
      early static growth phase (A1, A2) for at least 2 days or if the DF is in
      regression (C1, C2). However, when the DF is in the static growth phase for 3 or
      4 days (B1, B2), their morphological and functional characteristics are
      different. The CL controlls ovulation in the A and C groups and plays an
      abettor's roll in the B-group.

PMID- 11572439
TI  - Effect of antioxidants on preservation of motility,viability and acrosomal
      integrity of equine spermatozoa during storage at 5 degrees C.
AB  - Preservation of liquid semen at 5 degrees C is an important technique in the
      breeding management of horses. Oxidative damage to spermatozoa during storage is
      a potential cause of the decline in motility and fertility during hypothermic
      storage of liquid semen. The objective of this study was to evaluate the use of
      water-soluble and lipid-soluble antioxidants to improve the maintenance of
      motility of equine spermatozoa at 5 degrees C during storage for 72 to 96 h. In
      Experiment 1, the effect of addition of catalase on the maintenance of motility,
      viability and acrosomal integrity was determined. Semen was collected, and these
      treatments were applied: catalase (0, 100 or 200 U/mL) in nonfat, dried skim milk
      extender (NFDSM; with or without seminal plasma) or 10% seminal plasma + NFDSM.
      Motility was determined by computerized semen analysis (CASA) at 0, 24, 48 and 72
      h. Viability and acrosomal integrity were determined at 72 h of storage. There
      was no significant treatment effect on the maintenance of sperm motility during
      72 h storage. In Experiment 2, the effect of adding lipid-soluble antioxidants on
      maintenance of motility was evaluated. Semen was diluted to a final concentration
      of 25 x 10(6) sperm/mL in NFDSM containing butylated hydroxytoluene (BHT; 2.0,
      1.0, or 0.5 mM), Vitamin E (4.0, 2.0, 1.0 mM), or Tempo (2.0, 1.0, or 0.5 mM).
      Although the addition of BHT significantly reduced (P < 0.05) progressive
      motility during storage compared to the control, there were no positive treatment
      effects of either Vitamin E or Tempo on maintenance of motility. In Experiment 3,
      the effect of adding water-soluble antioxidants on maintenance of motility was
      evaluated. Semen was diluted in NFDSM containing these treatments: Trolox (2.0
      mM), Tempo (1.0 mM), Vitamin C (0.45 mg/mL), BSA (3% w/v), combinations of these
      antioxidants, or control. Adding these water-soluble antioxidants did not
      significantly improve the maintenance of motility during cooled storage at 5
      degrees C. In conclusion, adding the enzyme scavenger, catalase, or a variety of
      lipid- and water-soluble antioxidants did not significantly improve the
      maintenance of motility during liquid semen storage at 5 degrees C.

PMID- 11572440
TI  - Effect of activin-a on goat granulosa cell steroidogenesis.
AB  - Growth factors are said to play a significant role in the development of ovarian
      follicles. We wished to measure the content of one growth factor, activin-A in
      goat ovarian follicles, and study its effect on goat granulosa cells
      steroidogenesis. The follicular fluid content of activin-A from small, medium and
      large antral follicles was determined by two-site enzyme immunoassay. The results
      showed that activin-A concentration in the follicular fluid increased as the size
      of the follicle increased and, thus, may act as a local regulator of follicle
      development. To examine this possibility, the effect of increasing concentration
      of activin-A (0, 1, 10, 100 ng/mL) on differentiated goat granulosa cells
      steroidogenesis was evaluated in vitro for 48 hours in a chemically defined
      medium. Activin-A treatment resulted in a significant inhibition of progesterone
      production concomitant with a significant stimulation of estradiol production.
      These results were confirmed by time-effect of 50 ng/mL activin-A on goat
      granulosa cells steroidogenesis for 24, 48 and 72 hours. Granulosa cells
      displayed differential steroidogenic responses to activin-A, estradiol production
      becoming enhanced and progesterone production suppressed. Based on these
      findings, it appears that activin-A is a local regulator of goat granulosa cell
      steroidogenesis, and may act to promote granulosa cell differentiation and
      inhibit its luteinization.

PMID- 11572441
TI  - Administration of antiprogestin J956 for contraception in bears: a
      pharmacological study.
AB  - Effective and reversible control of reproduction in bears is highly desirable for
      conservation and management programs in zoos to establish genetically variable ex
      situ populations of bears within the constraints of limited space in captivity.
      The reproductive physiology of bears is characterized by two main traits-
      seasonality and delayed implantation, which is progesterone dependent. This
      offers the opportunity to interrupt early pregnancy by short-term administration
      of antiprogestins. The aim of the present study was to investigate the
      pharmacological characteristics of antiprogestin J956 to establish an efficient
      contraceptive protocol for administration of J956 in captive bears. The J956
      binds to the uterine progesterone receptor of bears (n = 2) with almost the same
      relative binding affinity (1.25) as progesterone. The blood serum level of J956
      after oral (on four consecutive days) and single parenteral administration was
      determined by a modified progestin receptor assay. The relative bioavailability
      of J956 after oral administration was approximately 10% of the parenteral
      administration. The estimated half-life was 12 to 16 hours after oral
      administration. Parenteral treatment of J956 (10 mg/kg body mass) led to sustain
      plasma concentrations (6.4 +/- 1.3 ng/mL) in one black bear and in five brown
      bears. The plasma level lasted for almost 2 months. Oral and low dosage
      parenteral (1 mg/kg body mass) administration of J956 had no effect on ongoing
      pregnancies in bears. Whereas single parenteral administration with higher
      dosages of J956 (7.5 to 10 mg/kg body mass) efficiently prevented implantation of
      early embryos in eight female captive bears.

PMID- 11572442
TI  - The effects of ph, osmolarity and urine contamination on equine spermatozoal
      motility.
AB  - Urospermia has been reported as a cause of infertility in numerous species. The
      detrimental effects of urine on spermatozoa are due, at least in part, to changes
      in pH and osmolarity. Semen was collected and subjected to conditions of varying
      pH (Experiment 1), of varying osmolarity (Experiment 2), and various quantities
      and concentrations of urine (Experiment 3) and effects on motility were recorded.
      Finally, semen was contaminated with urine and then either of 2 semen extenders
      was added, with or without centrifugation, in an attempt to alleviate the
      detrimental effect of urine on motility (Experiment 4). The results of these
      experiments showed that alterations in pH and osmolarity negatively affected
      stallion sperm motility. Optimal pH and osmolarity appeared to be approximately
      7.7 and 315, respectively. Contamination of the ejaculate with urine
      significantly decreased sperm motility. Smaller quantities of dilute urine were
      less detrimental than larger quantities of dilute urine, and dilute urine was
      less detrimental than more concentrated urine. The addition of semen extender
      restored the motility of urine contaminated semen to that of the uncontaminated
      control, however centrifugation to remove urine provided no significant
      advantage.

PMID- 11572443
TI  - Effect of external cryoprotectants as membrane stabilizers on cryopreserved
      rainbow trout sperm.
AB  - The process of freezing and thawing induces certain cellular damage in rainbow
      trout (Oncorhynchus mykiss) spermatozoa. We have previously demonstrated that
      after freezing and thawing decreased fertility in rainbow trout (Oncorhynchus
      mykiss) spermatozoa, is related to sublethal damage to the plasma membrane.
      External cryoprotectants are known to stabilize the sperm cell membrane against
      such damage. In the current study, we used a basic freezing extender containing
      #6 Erdahl and Graham and 7% DMSO and added egg yolk, BSA, and a soybean-protein
      complex (DanPro S760) singly and in various combinations. To assess the effect of
      these cryoprotectants we evaluated the percentage of cells with progressive
      motility, permeability of cells to propidium iodide (viability) after exposure
      for 30 sec, 2, 5, 10 and 15 min. to hypo- and isoosmotic solutions of 10 and 300
      mOsm, and the in vitro fertility rate. Fertility trials were performed using 1.87
      x 10(7) spermatozoa/egg. Some of the tested stabilizers increased motility,
      increased viability, or reduced cell fragility after freezing and thawing.
      Nevertheless these quality improvements demonstrated by the "in vitro" tests do
      not always correlate with high fertility. The best membrane protection in terms
      of resistance to hypoosmotic shock was achieved when BSA and egg yolk were added
      to the extender. The highest fertility rates were obtained with DanPro S760 alone
      or in combination with BSA; the use of BSA with egg yolk did not improve this
      parameter. Our results demonstrated that some external cryoprotectants
      effectively increased membrane resistance during freezing and thawing, but some
      of the tested mixtures interfered with fertilization. Soybean protein concentrate
      provided good protection and increased fertility rates in cryopreserved trout
      spermatozoa.

PMID- 11572444
TI  - Evaluation of the early conception factor (ECF) test for the detection of
      nonpregnancy in dairy cattle.
AB  - The ability to detect conception and/or conception failure in cattle would be
      beneficial to producers in formulating reproductive management plans. A new
      diagnostic test, the early conception factor (ECF) test, has been developed
      forthis application yetthe accuracy of this test has not been adequately
      determined. The objectives of this study were to evaluate the effectiveness of
      the ECF test for detecting the nonpregnant cow, and to compare the reliability of
      serum versus milk ECF tests relative to actual pregnancy rates. In Trial 1,
      Holstein heifers were synchronized, the animals were bred (timed-AI), and serum
      ECF tests were performed 72 h later. Heifers exhibiting a negative ECF test after
      AI were re-synchronized, bred again, and re-tested for ECF for up to three
      services. Relative to actual pregnancy rates, a negative ECF test was correct
      (i.e., true negative) 38.5% of the time over the three services. In Trial II,
      Holstein heifers were bred (AI) after observed estrus and serum ECF tests
      conducted between Days 1 and 3 and Days 7 and 9 after AI. In this trial, only
      44.4% and 55.6% of the confirmed nonpregnant heifers were identified correctly by
      serum ECF analysis at Days 1 to 3 and Days 7 to 9 post-AI respectively. In Trial
      III, 40 lactating cows were synchronized, the animals were bred (AI), and serum
      and milk ECF tests were performed on Days 3, 9, 15, 21 and 30 after AI. Pregnancy
      diagnosis (ultrasound on Day 30 and palpation on Day 51) confirmed that 50% of
      the cows were pregnant to AI, while serum and milk ECF analysis indicated a 100%
      and 37.5% predicted pregnancy rate, respectively, at 30 d post-AI. Moreover,
      results of the serum and milk ECF tests disagreed with one another 36.9% of the
      time overall, while agreement between ECF and actual pregnancy rates were 50.6%
      and 45.6% for milk and serum respectively. Additionally in Trial III, a negative
      ECF result only identified 5% and 28.8% of nonpregnant cows overall for serum and
      milk tests respectively (i.e., true negatives), with a high incidence of false
      positive ECF results noted (47.5% and 31.3% for serum and milk, respectively).
      Collectively, these data indicate that the current ECF test cannot accurately
      identify the nonpregnant cow with the precision needed by the dairy producer.

PMID- 11572445
TI  - Persistent ovarian follicles in dairy cows: a therapeutic approach.
AB  - Anestrus is common during the postpartum period in high-producing dairy cows. In
      a previous investigation, we were able to diagnose persistent follicles of 8 to
      12 mm in anestrous cows. This report describes 2 consecutive studies. The
      objectives of the first were to 1) assess the association of persistent follicles
      with anestrus; and 2) evaluate 2 therapeutic treatments. In the second study, we
      compared the effectiveness of the best treatment established in Study 1 with the
      Ovsynch protocol. For Study 1, anestrous cows were considered to have a
      persistent follicle if it was possible to observe a single follicular structure >
      8 mm in the absence of a corpus luteum or a cyst in 2 ultrasonographic
      examinations performed at an interval of 7 d. At diagnosis (Day 0), cows were
      assigned to 1 of 3 treatment groups. Cows in Group GnRH/PGF (n=17) were treated
      with 100 microg GnRH i.m., and 25 mg PGF2alpha i.m. on Day 14. Cows in Group PRID
      (n=18) were fitted with a progesterone releasing intravaginal device (PRID,
      containing 1.55 g of progesterone) for 9 d and were given 100 microg GnRH i.m. at
      the time of PRID insertion, and 25 mg PGF2alpha i.m. on Day 7. Cows in Group
      Control (n=18) received no treatment. The animals were inseminated at observed
      estrus and were monitored weekly by ultrasonography until AI or 5 weeks from
      diagnosis. Blood samples were also collected on a weekly basis for progesterone
      determination. The mean size of persistent follicles on Day 0 was 9.4 +/- 0.04
      mm. Progesterone levels were < 0.2 ng/mL during the first 35 d in 16 of 18
      Control cows. Cows in the PRID group showed a lower persistent follicle rate
      (16.7% < 70.6% < 88.9%; P < 0.0001; PRID vs GnRH/PGF vs Control, respectively); a
      higher estrus detection rate (83.3% > 29.4% > 11.1%; P < 0.0001) and a higher
      pregnancy rate (27.8% > 5.9% > 0%; P = 0.02). For the second study, 145 cows with
      persistent follicles were randomly assigned to 1 of 2 treatment groups: cows in
      Group Ovsynch (n=73) were treated with 100 microg GnRH i.m. on Day 0, 25 mg
      PGF2alpha i.m. on Day 7, and 100 microm GnRH i.m. 32 h later. Cows in this group
      were inseminated 16 to 20 h after the second GnRH dose (Ovsynch protocol). Cows
      in Group PRID (n=72) were treated as those in the PRID group of Study 1, and were
      inseminated 56 h after PRID removal. Cows in the PRID group showed a higher
      ovulation rate (84.8% > 8.2%: P < 0.0001); a higher pregnancy rate (34.2% > 4.1%;
      P < 0.0001) and lower follicular persistence rate (22.2% < 63%; P < 0.0001) than
      those in Ovsynch. Our results indicate that persistent follicles affect cyclic
      ovarian function in lactating dairy cows. Cows with persistent follicles can be
      successfully synchronized and time inseminated using progesterone, GnRH and
      PGF2alpha but show a limited response to treatment with GnRH plus PGF2alpha.

PMID- 11572446
TI  - Effects of gonadotropins on bovine oocytes matured in TCM-199.
AB  - The effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
      during in vitro maturation of bovine oocytes in TCM-199 without serum were
      evaluated. Bovine oocytes with compact cumulus cells were collected from
      slaughterhouse-derived ovaries and cultured in Hepes-buffered TCM-199
      supplemented with 5 mg/mL BSA, 1 microg/mL estradiol-17beta, FSH (0, 0.015, 0.05,
      0.15, 1.5 or 15 ng/mL; Experiment 1), LH (0, 0.14, 1, 7 or 49 microg/mL;
      Experiment 2) and combinations of 1 or 10 ng/mL FSH and 1 or 10 microg/mL LH
      (Experiment 3) at 39 degrees C in 5% CO2 in air. After 22 h of maturation,
      cumulus expansion was estimated by scoring from 0 (no expansion) to 4 (full
      expansion of cumulus mass). In vitro fertilization was done with Percoll (45/90%)
      separated bull sperm at 1 x 10(6) sperm/mL in fert-TALP with 5 U/mL heparin. At
      18 to 20 h post-insemination, presumptive zygotes were transferred to a
      chemically defined medium (CDM-1) supplemented with 0.5% BSA and nonessential
      amino acids for 72 h and then moved to CDM-2, additionally supplemented with
      essential amino acids. Zygotes were cultured at 39 degrees C in 5% CO2, 5% O2 and
      90% N2 for 8 days. During Experiments 1 and 2, cumulus expansion increased in
      proportion to concentrations of FSH and LH. Cleavage rates and development to
      blastocysts were not significantly different among FSH and LH treatments. In
      Experiment 3, cumulus expansion of bovine oocytes was maximal when 1 ng/mL FSH
      and 1 microg/mL LH were added to IVM medium, but cumulus expansion again was not
      related to developmental ability, although cleavage rates were improved slightly
      (P<0.05) by the combination of LH and FSH. Blastocyst quality, estimated by the
      size of inner cell mass, was not different between combinations of FSH and LH,
      and the numbers of nuclei were not different. Although expansion of cumulus cells
      surrounding bovine oocytes was altered in response to FSH and/or LH in semi
      defined medium, cumulus expansion was not related to rates of cleavage or
      subsequent embryonic development in vitro. The effects of LH on cumulus expansion
      can be explained by as little as 1 part per 10, 000 contamination with FSH.

PMID- 11572447
TI  - Pregnancy-associated glycoproteins (PAG) detection in milk samples for pregnancy
      diagnosis in dairy goats.
AB  - In ruminants, glycoproteins synthesized in the outer layers of the trophoblast
      enter the maternal bloodstream. The assay of their concentration in plasma or in
      serum can be used for pregnancy diagnosis and to indicate feto-placental health
      status. In this study, concentrations of the pregnancy-associated glycoprotein
      (PAG) were investigated in the milk of dairy goats. The mean concentrations of
      PAG in milk were significantly higher in pregnant than in non-pregnant goats
      throughout the sampling period. Positive milk PAG levels were found in all
      pregnant animals from Day 32 after breeding, but remained at negative values in
      nonpregnant ones. This study reports for the first time a pregnancy diagnosis
      based on milk concentrations of PAG, that could be of great use on the farm.

PMID- 11572449
TI  - Increase in milk and body temperature of cows as a sign of embryo entry into the
      uterus.
AB  - The objective of the first stage of these studies was to investigate whether
      temperature increases in the milk and body of cows during the early period of
      pregnancy. We studied 94 pregnant and 116 nonpregnant cows, and the temperatures
      were measured daily beginning 24 days after insemination. In addition,
      progesterone levels in milk were measured twice (on Days 21 and 24 after
      insemination), and examinations per rectum were conducted to determine pregnancy.
      Data analysis showed that in almost 90% of the pregnant cows milk temperature
      increased by 0.64 degrees C some time between Days 5 and 12 after insemination.
      This increase in milk temperature was highly significant and corresponded with a
      0.46 degrees C increase in body temperature. There was no increase in the milk or
      body temperature in nonpregnant cows. After discovering in the first stage that a
      high percentage of pregnant cows experienced both milk and body temperature
      increases, we focused our attention in the second stage of the study on the
      question of whether this increase in temperatures might be due to an immune
      response of the mother to the entry of the embryo into the uterus. In this stage
      we conducted three different experiments on another group of animals consisting
      of 309 cows and heifers. The experiments included analysis of progesterone,
      estradiol, cortisol and PGE2 levels in the blood serum of the cows and heifers;
      an estimation of the pyrogenic activity of PGE1, PGE2 and progesterone; and
      measurements of body temperature in the heifers before and after embryo transfer.
      The results of these experiments suggested that an increase in milk and body
      temperature could be an indicator of an immune response of the mother to the
      entry of the embryo into the uterus.

PMID- 11572448
TI  - A novel automated fluorometric assay to evaluate sperm viability and fertility in
      dairy bulls.
AB  - The artificial insemination (AI) industry is in need of an objective and rapid,
      but inexpensive method to evaluate frozen thawed bull semen ejaculates. This
      study presents a new fluorescence method that uses an automatized fluorometer and
      fluorophore stain propidium iodide that stains only those cells with damaged
      membranes. The fluorescence of the semen sample and the totally killed subsample
      were measured simultaneously, and viability was calculated. Every semen batch was
      analyzed before use in AI. For fertility evaluation, the nonreturn rates (NR%)
      obtained from 92,120 inseminations with the analyzed batches were recorded from
      166 bulls (436 batches). This study confirms a 3.9% better NR% for the Finnish
      Holstein-Friesian breed than for Finnish Ayrshire. There was a clear seasonality
      in NR%: it differed (5.3%) significantly, being best in summer to autumn (June to
      October) and lowest in winter (January to March). The fluorometer method was fast
      and easy. The correlation between the total number of viable spermatozoa in an
      insemination dose and field fertility was low but significant (r = 0.051, P =
      0.016), suggesting that the plasma membrane integrity evaluation can serve as a
      cost-beneficial quality control method of frozen-thawed semen at bull stations.

PMID- 11572450
TI  - Trichoderma koningii as a biomineralizing fungous agent of calcium oxalate
      crystals in typical Argiudolls of the Los Padres Lake natural reserve (Buenos
      Aires, Argentina).
AB  - The aim of the present study, performed on typical Argiudolls in a natural
      reserve with little or no anthropic impact, was to characterize the fungous
      biomineralizing process of calcium oxalate crystals in organic horizons of the
      soil. The chosen sites possessed different plant cover, identified as acacia
      woods and grassy meadows with particular micro environmental conditions that have
      differing effects in the process of biomineralization. The contribution of the
      plant material in the soil is a key factor since 1) it generates the particular
      composition of the organic horizons, 2) it determines the nature of decomposing
      organisms, and 3) it affects the presence, composition and development of
      biominerals. According to the results obtained, the acacia woods prove to be a
      site comparatively more favorable to the fungous biomineralizing process. This
      makes itself manifest in the greater abundance and development of crystals in the
      organic horizons of the soil, resulting in whewellite (CaC2O4.H2O) and weddellite
      (CaC2O4.(2+x) H2O) regarding biomineral species developed, the latter being the
      major component. The observation of both species of biominerals is noteworthy
      since it represents the first cited in the country. The isolated fungous
      organisms were Trichoderma koningii, and Absidia corymbifera. T. koningii was
      identified as the most active biomineralizing organism thus constituting the
      first reference to indicate this species as a biomineral producing agent.

PMID- 11572451
TI  - Physiological and genetic characteristics of two bacterial strains utilizing
      phenoxypropionate and phenoxyacetate herbicides.
AB  - Two strains, Rhodoferax sp. P230 and Delftia (Comamonas) acidovorans MCI, have
      previously been shown to carry activities for the degradation of the two
      enantiomers of (RS)-2-(2,4-dichlorophenoxy-)propionate (dichlorprop) and (RS)-2
      (4-chloro-2-methylphenoxy-)propionate (mecoprop) and, in addition, are capable of
      degrading phenoxyacetate derivatives 2.4-dichlorophenoxyacetate (2,4-D) and 4
      chloro-2-methylphenoxyacetate (MCPA). Metabolism of the herbicides is initiated
      by alpha-ketoglutarate-dependent dioxygenases for both enantiomers of the
      phenoxypropionate herbicides and for 2,4-D. These activities were constitutively
      expressed for both enantiomers of dichlorprop in strain MC1 and for the
      Renantiomer in strain P230. Enzyme activities for the complete degradation of
      phenoxyacetate and phenoxypropionate herbicides were induced during incubation on
      either of these herbicides. Strain MC1 has about threefold higher activities for
      the degradation of dichlorprop and for growth on this substrate (mumax = 0.15 h(
      1)) than strain P230; the maximum growth rate on 2,4-D amounts to 0.045 h(-1)
      with strain MC1. Dichlorprop is utilized faster than mecoprop and the R
      enantiomers are cleaved with higher rates than the S-enantiomers. The degradation
      of the chlorophenolic intermediates seems to proceed via the modified ortho
      cleavage pathway as indicated by activities of the respective enzymes. The
      enzymatic results were supported by genetic investigations by which the presence
      of the genes tfdB (encoding a dichlorophenol hydroxylase), tfdC (encoding a
      chlorocatechol 1,2-dioxygenase) and tfdD (encoding a chloromuconate
      cycloisomerase) could be demonstrated in both strains by PCR after application of
      respective primers. The presence of the tfdA gene (encoding a 2,4-D/alpha
      ketoglutarate dioxygenase) was only shown for strain P230 but was lacking in
      strain MC1. Sequence analysis of the tfd gene fragments revealed high homology to
      the degradative genes of other proteobacterial strains degrading chloroaromatic
      compounds. Strain MC1 carries a plasmid of about 120 kb which apparently harbors
      herbicide degradative genes as concluded from deletion mutants which have lost
      2,4-D[phenoxalkanoate]/alpha-ketoglutarate dioxygenase activities for cleavage of
      the R- and S-enantiomer, and of 2,4-D. For strain P230, no plasmid could be
      demonstrated; the activity was stably conserved in this strain during growth
      under nonselective conditions.

PMID- 11572452
TI  - Isolation and characterization of enterocin BC25 and occurrence of the entA gene
      among ruminal gram-positive cocci.
AB  - Enterocin BC25, a bacteriocin produced by Enterococcus faecium BC25 isolated from
      the rumen of cow was purified to homogeneity and sequenced. Twenty amino acids
      were identified in the peptide chain (TTHSGKYYGNGVYCT-KNKCT), identical to the N
      terminal sequence of enterocin A. The DNA sequence of the enterocin BC25
      structural gene and putative immunity protein exhibited high similarity to the
      entA gene. The occurrence of a 726 bp amplicon containing the enterocin A
      structural gene was studied among gram-positive ruminal cocci by PCR. Our results
      showed wide occurrence of the entA structural gene among ruminal enterococcal and
      streptococcal bacterial strains tested, and indicate variable ability to express
      bacteriocin production and resistance.

PMID- 11572453
TI  - Two pathogenesis-related peroxidases in greengram (Vigna radiata (L.) wilczek)
      leaves and cultured cells induced by Macrophomina phaseolina (Tassi) Goid. and
      its elicitor.
AB  - An elicitor has been isolated from Macrophomina phaseolina, the root rot and leaf
      blight pathogen of greengram. Suspension-cultured cells of greengram were
      established which responded to the fungal elicitor. When greengram leaves were
      inoculated with M. phaseolina two new peroxidases appeared. Similarly, two new
      peroxidases could be detected in suspension-cultured greengram cells when treated
      with the fungal elicitor. These peroxidases were purified by column
      chromatography and their molecular masses were 27 and 38 kDa. The new peroxidases
      detected in both leaves and cultured cells appear to be similar with the same
      molecular weights.

PMID- 11572454
TI  - Improvement in bioavailability of tricalcium phosphate to Cymbopogon martinii
      var. motia by rhizobacteria, AMF and Azospirillum inoculation.
AB  - The interactive effects of phosphate solubilizing bacteria, N2 fixing bacteria
      and arbuscular mycorrhizal fungi (AMF) were studied in a low phosphate alkaline
      soil amended with tricalcium insoluble source of inorganic phosphate on the
      growth of an aromatic grass palmarosa (Cymbopogon martinii). The microbial
      inocula consisted of the AM fungus Glomus aggregatum, phosphate solubilizing
      rhizobacteria Bacillus polymyxa and N2 fixing bacteria Azospirillum brasilense.
      These rhizobacteria behaved as "mycorrhiza helper" and enhanced root colonization
      by G. aggregatum in presence of tricalcium phosphate at the rate of 200 mg kg(-1)
      soil (P1 level). Dual inoculation of G. aggregatum and B. polymyxa yielded 21.5 g
      plant dry weight (biomass), while it was 21.7 g in B. polymyxa and A. brasilense
      inoculated plants as compared to 14.9 g of control at the same level. Phosphate
      content was maximum (0.167%) in the combined treatment of G. aggregatum, B.
      polymyxa and A. brasilense at P1 level, however acid phosphatase activity was
      recorded to be 4.75 pmol mg(-1) min(-1) in G. aggregatum, B. polymyxa and A.
      brasilense treatment at P0 level. This study indicates that all microbes
      inoculated together help in the uptake of tricalcium phosphate which is otherwise
      not used by the plants and their addition at 200 mg kg(-1) of soil gave higher
      productivity to palmarosa plants.

PMID- 11572455
TI  - Isolation of a benzoate-utilizing Pseudomonas strain from soil and production of
      catechol from benzoate by transpositional mutants.
AB  - Pseudomonas sp. Ba-0511 was isolated from soil by enrichment cultivation on a
      medium containing 6 mg/ml of sodium benzoate. The bacterium could grow on a
      medium containing 20 mg/ml of sodium benzoate by a successive enrichment culture.
      One hundred and twelve transpositional mutants of the bacterium produced catechol
      from benzoate and accumulated it outside of the cells. Among the mutants, strain
      BA+63 produced a maximal amount of catechol (2.3 mg/ml) from 6 mg/ml of sodium
      benzoate after growing for 10.5 h. The conversion rate of benzoate to catechol
      was 50% on a molar basis. The catechol production by the resting cells increased
      in the presence of glycerol, and the maximal amount of catechol produced from 6
      mg/ml of sodium benzoate reached 3.3 mg/ml at the conversion rate of 72% after 5
      h of incubation. The resting cells converted m-methylbenzoic acid to 3- and 4
      methylcatechol and m-chlorobenzoic acid to 3- and 4-chlorocatechol.

PMID- 11572456
TI  - Screening for trbB- and traG-like sequences by PCR for the detection of
      conjugative plasmids in bacterial soil isolates.
AB  - The transfer regions of different conjugative plasmids show significant
      similarities in the genetic organization and in the amino acid sequence of some
      gene products, especially of proteins from the traG or trbB family. These
      similarities are also evident on the level of the nucleotide sequences. On the
      basis of conserved DNA regions we designed degenerate PCR primer pairs to detect
      specifically tra regions within a collection of bacterial clones isolated from an
      agricultural soil. Most of the potential transfer-proficient indigenous bacterial
      isolates were able to mobilize a derivative of the nonconjugative IncQ plasmid
      RSF1010 into recipient strains. With the help of the primers it should be
      possible to evaluate the genetic potential for horizontal gene transfer carried
      out by conjugative plasmids.

PMID- 11572457
TI  - Strain typing of polish Leptosphaeria maculans isolates supports at the genomic
      level the multi-species concept of aggressive and non-aggressive strains.
AB  - 47 Polish isolates of the blackleg fungus Leptosphaeria maculans (Phoma lingam)
      were compared with eight well-defined reference strains from Germany, France,
      Denmark, Australia and one Polish isolate of Phoma nigrificans. The isolates were
      tested (i) for growth characteristics, (ii) for their ability to form
      sirodesmins, (iii) for cellulolytic enzymes, and (iv) for pathotype
      differentiating molecular markers generated by RAPD-PCR, PCR analysis with
      pathotype-specific primer pairs and PFGE. With two exceptions all Polish isolates
      do not form sirodesmins. grow rapidly without penetrating into the substrate and
      form in most cases yellow or brown pigments in Czapek-Dox liquid cultures. With
      respect to cellulase secretion and molecular fingerprinting Polish A strains
      (aggressive) fit into the general picture of the aggressive pathotype group,
      whereas the NA isolates (non-aggressive) display a higher degree of
      heterogeneity. This matches with inoculation tests on rape seedlings, which
      revealed a considerable number of isolates ranging in aggressivity between the
      conventional A and NA pathotype group. Molecular fingerprinting techniques
      unequivocally sorted intermediately aggressive isolates into the NA pathotype
      group. Isolate Ph Bial, which produces sirodesmin but groups within NA isolates
      according to molecular and physiological markers, may represent a novel third
      group besides A and NA strains with intermediate aggressivity (IA). We hybridized
      Southern blots of electrophoretically separated chromosomes with radioactively
      labelled PCR fragments used for differentiation between A and NA isolates. The
      specificity of diagnostic PCR amplicons is reflected at the genomic level. The A
      probe reveals a single hybridizing chromosome exclusively in A strains. The NA
      probe reveals several chromosomes and is specific for the NA pathotype group.
      Chromosomes from intermediately aggressive strains are equally well recognized by
      the NA probe as are Polish isolates with low aggressivity and give no signal with
      the A probe. Both diagnostic DNA sequences are highly specific for the pathotype
      group they were derived from. The lack of correspondence of both genetic elements
      between A and NA strains strongly supports the idea of ascribing the pathotype
      groups to different species. Whereas the A pathotype group is genetically
      homogeneous and congruent with the species Leptosphaeria maculans, the NA group
      needs to be revised taxonomically. NA isolates will presumably have to be split
      into several independent species.

PMID- 11572458
TI  - Detection of aster yellows phytoplasma in false flax based on PCR and RFLP.
AB  - False flax (Camelina sativa L.) plants were found to be infected with a yellows
      type disease caused by a phytoplasma in experimental plots at the Edmonton
      Research station. Alberta, Canada. Typical phytoplasmas were detected in the
      phloem cells in ultrathin sections from leaf midrib tissues examined by electron
      microscopy. These observations were supported by polymerase chain reaction (PCR)
      using two primer pairs, R16 F2n/R2 and R16(1)F1/R1, derived from phytoplasma rDNA
      sequences. Aster yellows (AY) and potato witches'-broom (PWB) phytoplasma DNA
      samples served as controls and were used to study group relatedness. In a direct
      PCR assay, DNA amplification with universal primer pair R16F2n/R2 gave the
      expected PCR products of 1.2 kb. Based on a nested-PCR assay using the latter PCR
      products as templates, and a specific primer pair, R16(1)F1/R1, designed on the
      basis of AY phytoplasma rDNA sequences, a PCR product of 1.1 kb was obtained from
      each phytoplasma-infected false flax and AY sample, but not from PWB phytoplasma
      and healthy controls. DNA amplification with specific primer pair R16(1)F1/R1 and
      restriction fragment length polymorphism indicated the presence of AY phytoplasma
      in the infected false flax sample. This is the first reported characterization of
      AY phytoplasma in false flax.

PMID- 11572459
TI  - Pythium perplexum isolated from soil in France: morphology, molecular
      characterisation and biological control.
AB  - Pythium perplexum (F-926) was isolated from a soil sample taken in the Burgundy
      region in France. In 1907, it was mistakenly described by Bulter as P. vexans.
      Despite morphological resemblance, the comparison between the internal
      transcribed spacer 1 regions of the ribosomal DNA of the two fungi leaves no
      doubt of their different identities. P. perplexum was found to be highly
      pathogenic to cucumber seedlings. Damping-off disease of cucumber caused by P.
      perplexum can effectively be controlled by using the soil bacterium Serratia
      plymuthica (B-781). The details of the morphology and the molecular
      characterisation of P. perplexum and its biological control with S. plymuthica
      are described here.

PMID- 11572460
TI  - Suppression of damping-off in maize seedlings by Pseudomonas corrugata.
AB  - Two strains of Pseudomonas corrugata, (1 and 7), isolated from subtropical and
      temperate soils in Sikkim Himalaya, respectively, were subjected to Petri-dish as
      well as plant-based bioassay to examine their potential for disease suppression
      against three major pathogens of maize. A mixture of Pythium ultimum, P.
      arrhenomanes and Fusarium graminearum was introduced in the soil; maize seed
      inoculated with one of the two strains of Pseudomonas corrugata (1 or 7) were
      sown in pots containing such soil. The bacterial inoculation resulted in
      significant disease suppression as well as growth promotion of seedlings. The
      bacterial strains were also evaluated for their intrinsic antibiotic resistance
      against a range of concentrations of ten antibiotics. While the bacteria were
      found to be sensitive to gentamycin and rifampicin, they exhibited resistance
      against ampicillin, carbenicillin and penicillin, even at high concentrations.

PMID- 11572461
TI  - Isolation of Bacillus thuringiensis from intertidal brackish sediments in
      mangroves.
AB  - Intertidal brackish sediments in mangroves were examined for isolation of
      Bacillus thuringiensis strains with novel toxicity spectra. A total of 18 B.
      thuringiensis isolates were recovered from eight sediment samples (36.4%) out of
      22 samples tested. The frequency of B. thuringiensis was 1.3% among the colonies
      of Bacillus cereus/B. thuringiensis group. While five isolates were allocated to
      the four H serogroups, the majority of the isolates were serologically untypable
      or untestable. Two isolates belonging to the serovar israelensis/tochigiensis
      (H14/19) exhibited strong toxicities against larvae of the mosquito, Culex
      pipiens molestus, and mammalian cells (sheep erythrocyte and two human cancer
      cell lines) in vitro. The other 16 isolates showed no toxicity against the
      mosquito and mammalian cells. None of the isolates showed larvicidal activity
      against the diamondback moth, Plutella xylostella. Strong lectin activities
      against sheep erythrocytes were associated with two serologically untestable
      isolates and an H3 isolate.

PMID- 11572463
TI  - Effects of inhibition of nitric oxide synthase on basal anterior segment ocular
      blood flows and on potential autoregulatory mechanisms.
AB  - Experiments were undertaken to determine the role played by nitric oxide (NO) in
      basal ocular blood flow in the anterior aspect of the eye. Subsequent studies
      focused on existence of autoregulatory mechanisms and on the potential
      involvement of NO. Cats were anesthetized with pentobarbital (36 mg/kg, i.p.). A
      femoral artery and vein were cannulated for measuring blood pressure and for drug
      administration, respectively. Anterior segment blood flow was measured in a
      continuous fashion from the long posterior ciliary artery (LPCA) using ultrasonic
      flowmetry and from the anterior choroid using laser-Doppler flowmetry. A needle
      was placed into the anterior chamber, and autoregulatory mechanisms were studied
      by decreasing ocular perfusion pressure via stepwise elevations of IOP. Non
      selective inhibition of NO synthase with L-NAME (20 mg/kg, i.v.) significantly
      decreased basal blood flow from both sites. L-NAME (5 mg/kg, i.v.) was without
      effect as was D-NAME (25 mg/kg, i.v.). Increasing IOP produced a linear decrease
      on LPCA blood flow indicating absence of autoregulation. In contrast, stepwise
      elevation of IOP produced a delayed, non-linear response in the anterior choroid
      suggestive of a strong autoregulatory response. Neither response to elevated
      ocular perfusion pressure was further altered by inhibition of NO synthase with L
      NAME (20 mg/kg, i.v.). The results confirm previous reports that nitric oxide
      plays a pivotal role in maintenance of basal ocular blood flow. Autoregulation
      was not seen in the LPCA. In contrast, there was a clear autoregulatory response
      in the anterior choroid, although neither response was altered by inhibition of
      NO synthase.

PMID- 11572462
TI  - Levobetaxolol (Betaxon) and other beta-adrenergic antagonists: preclinical
      pharmacology, IOP-lowering activity and sites of action in human eyes.
AB  - The pharmacological characteristics of levobetaxolol, a single active isomer of
      betaxolol, were determined and compared with activities of other beta
      adrenoceptor antagonists. Levobetaxolol (43-fold beta1-selective) exhibited a
      higher affinity at cloned human beta1 (Ki = 0.76 nM) than at beta2 (Ki = 32.6 nM)
      receptors, while dextrobetaxolol was much weaker at both receptors. Levobetaxolol
      potently antagonized functional activities at cloned human beta1 and beta2
      receptors, and also at guinea pig atrial beta1, tracheal beta2 and rat colonic
      beta3 receptors (IC50s = 33.2 nM, 2970 nM and 709 nM, respectively). Thus,
      levobetaxolol was 89-times beta1-selective (vs beta2). Levobetaxolol (Ki = 16.4
      nM) was more potent than dextrobetaxolol (Ki = 2.97 microM) at inhibiting
      isoproterenol-induced cAMP production in human non-pigmented ciliary epithelial
      cells. Levobunolol and (l)-timolol had high affinities at beta1 and beta2
      receptors but were considerably less beta1-selective than levobetaxolol. Levo-,
      dextro- and racemic-betaxolol exhibited little or no affinity, except at sigma
      sites and Ca2+-channels (IC50s > 1 microM), at 89 other receptor/ligand binding
      sites. Levobetaxolol exhibited a micromolar affinity for L-type Ca2+-channels. In
      conscious ocular hypertensive cynomolgus monkeys, levobetaxolol was more potent
      than dextrobetaxolol, reducing intraocular pressure by 25.9+/-3.2% at a dose of
      150 microg/eye (n = 15-30). Quantitative [3H]-levobetaxolol autoradiography
      revealed high levels of binding to human ciliary processes, iris, choroid/retina,
      and ciliary muscles. In conclusion, levobetaxolol is a potent, high affinity and
      beta1-selective IOP-lowering beta-adrenoceptor antagonist.

PMID- 11572464
TI  - Toxic effects of mitomycin-C on cultured ciliary process cells and trabecular
      meshwork cells.
AB  - Mitomycin-C has recently become an adjunct medication for inhibition of
      fibroblast proliferation in glaucoma filtering procedures. Prolonged
      postoperative ocular hypotony has been a frequent complication of trabeculectomy
      with mitomycin-C. In order to characterize the hypotony mechanism, we compared
      the toxic effects of mitomycin-C on cultured rabbit ciliary process cells and
      trabecular meshwork cells. The results indicate that mitomycin-C has a more
      marked effect on ciliary process cells on 3H-thymidine uptake than on trabecular
      meshwork cells at concentrations ranging from 10(-1) to 10(-5) mg/ml after 3-, 5-
      and 60-min treatment, respectively. The living cells after mitomycin-C treatment
      were estimated with MTT assay that was converted tetrazolium dye of living cells
      only into insoluble purple formazan crystals within mitochondria. In the presence
      of mitomycin-C for 3, 5, and 60 min, the cellular MTT values in ciliary process
      cells were more decreased than in trabecular meshwork cells. Depolarization of
      the trabecular meshwork cells with 50 mM KCl led to an increase in intracellular
      calcium concentration, whereas application of mitomycin-C at 10(-3) mg/ml
      resulted in decrease of KCl-induced intracellular calcium increase. Mitomycin-C
      (10(-3) mg/ml) decreased cAMP concentration in ciliary process cells following 3-
      and 5-min treatment; however, it did not significantly affect the cellular cAMP
      concentration after only a 1-min exposure. Mitomycin-induced marked ladder
      pattern of DNA fragmentation was observed in ciliary process tissues after
      treatment with 10(-1) mg/ml of mitomycin-C for 3 and 5 min. However, the DNA
      pattern in trabecular meshwork tissues was not obviously affected by mitomycin-C.
      These findings from our results indicate that mitomycin-induced ocular hypotony
      may result from damage to both ciliary process and trabecular meshwork tissues.

PMID- 11572465
TI  - The changes of vitreous pH values in an acute glaucoma rabbit model.
AB  - The changes of vitreous pH values under acute glaucoma status have never been
      reported. In this study, we measured the changes of vitreous pH values in an
      acute glaucoma rabbit model. Under ketamine and xylazine anesthesia, the anterior
      chamber of the right eye of New Zealand white rabbits was cannulated and
      connected to a polygraph for continuous intraocular pressure (IOP) monitoring and
      a mini-pump for persistent injection of viscoelastic substance, Healon GV. The
      measurement of vitreous pH was done by inserting a pH probe via a third opening
      through the sclera into the vitreous. Different IOP levels were maintained by
      varied amounts of Healon GV injections into the anterior chamber. The changes of
      vitreous pH values following the intracameral injections were recorded and
      evaluated. The changes of vitreous pH values were minimal when IOPs were
      maintained at lower than 35 mmHg. Vitreous pH values decreased significantly from
      7.32 to less than 7.03, when the IOPs were kept at 70 mmHg or higher. However,
      the decrease of pH values was reversible if IOP was held at 70 mmHg for less than
      10 minutes and then reduced to normal level at once. In addition, with MTT
      viability assay, it was noted that the decrease in vitreous pH was associated
      with a higher percentage of retinal cell death.

PMID- 11572466
TI  - Endothelin-induced changes of secondary messengers in cultured corneal
      endothelial cells.
AB  - The effect of endothelins on corneal endothelial cells is not well understood. We
      have investigated the effects of endothelin-1 (ET-1), endothelin-2 (ET-2) and
      endothelin-3 (ET-3) on bovine corneal endothelial cellular proliferation and the
      secondary messenger changes in cells in the presence of ET-1. It was found that
      the 3H-thymidine uptake was enhanced by ET-1 significantly, whereas ET-2 and ET-3
      had no effect. ET-1 remarkably affects the increase of corneal endothelial cells
      on 3H-thymidine, 3H-leucine, and 3H-uridine uptakes in a dose-dependent manner.
      The 50% effective concentrations (EC50) for ET-1, as measured by 3H-thymidine
      uptake, 3H-uridine uptake, and 3H-leucine uptake were 10(-8.78) M, 10(-8.53) M
      and 10(-8.04) M, respectively. It was found that endothelin-1 increased
      intracellular calcium concentration by using the method of preloading with Fura-2
      AM and assaying with spectrophotometry. The cellular IP1, IP2, and IP3 were also
      stimulated in the presence of ET-1. Moreover, ET-1 enhanced the basal cellular
      cAMP and cGMP concentrations in corneal endothelial cells in a dose-dependent
      manner. Immunofluorescent staining revealed that ET-1 increased the fibronectin
      protein concentration and changed protein distribution in corneal endothelial
      cells. These findings indicate that endothelin-1 increases in cell proliferation
      and biological changes may be involved in changing intracellular calcium
      mobility, increasing intracellular phosphoinositides, enhancing intracellular
      cGMP and cAMP accumulation, and fibronectin protein synthesis.

PMID- 11572467
TI  - Management of postvitrectomy diabetic vitreous hemorrhage with tissue plasminogen
      activator (t-PA) and volume homeostatic fluid-fluid exchanger.
AB  - The incidence of recurrent vitreous hemorrhage of proliferative diabetic
      retinopathy following posterior vitrectomy ranges from 29% to 75% in reported
      series. Fluid-gas exchange and vitreous cavity lavage are the popular methods of
      treating this kind of recurrent hemorrhage. The fluid-gas exchange cannot offer
      clear vision immediately after the procedure. To improve the function of the
      classic vitreous cavity lavage, we designed a volume homeostatic fluid-fluid
      exchanger - Chen's I/A device. Tissue plasminogen activator (t-PA) is a protease
      that preferentially converts fibrin-bound plasminogen to the active proteolytic
      enzyme, plasmin. It has been clinically and experimentally proven effective in
      lysis of postvitrectomy blood clot and fibrin formation. When the blood clot is
      formed in the vitreous cavity, intravitreal injection of t-PA can convert
      plasminogen to plasmin and remove the clot. From July 1999 to January 2000, ten
      eyes of postvitrectomy diabetic vitreous hemorrhage (PDVH) were collected. In
      each case, 4 days after intravitreal injection (IVI) of t-PA (30 microg),
      vitreous cavity lavage was performed with Chen's I/A device. Of these cases, 8
      eyes (80%) experienced an immediate clearing of the vitreous cavity. Early
      complications included anterior hyaloid fibrovascular proliferation (2 eyes) and
      postoperative intraocular pressure elevation (3 eyes). On the basis of the
      results of this study, our conclusion is that volume homeostatic vitreous cavity
      lavage, combined with intravitreal injection of t-PA, is an excellent method for
      treatment of postvitrectomy diabetic vitreous hemorrhage but, in cases of PDVH
      with iris rubeosis, the advantage of this procedure is uncertain.

PMID- 11572468
TI  - Intrinsic inhibition of aldose reductase.
AB  - The development of aldose reductase inhibitors for the treatment of diabetic
      complications, such as cataract and retinopathy, has been of intense interest in
      the pharmaceutical community for the last 20 years. To date, aldose reductase
      inhibitors have been synthetically developed from leads obtained from in vitro
      screening studies. Recently, we have observed that mammalian tissues contain
      intrinsic inhibitors of aldose reductase, which may be used as potential drugs
      for treating diabetic complications with potentially less side effects than
      synthetic aldose reductase inhibitors. Intrinsic inhibitor(s) of aldose reductase
      have been observed in the methanolic extracts from rat and human kidneys and
      bovine lenses that were subjected to a number of chromatographic techniques,
      including counter current chromatography, flash chromatography, gel filtration
      and high pressure liquid chromatography. This inhibition results from a direct
      interaction between the inhibitor and enzyme. The intrinsic inhibitor, present in
      the lipophilic fraction of human kidney and bovine lens extracts, can easily
      penetrate into the lens to inhibit sugar alcohol formation. Intraperitoneal
      injection of partially purified bovine lens extract inhibited lens polyol
      formation in young rats fed 50% galactose diet.

PMID- 11572469
TI  - Naphthoquinone-Induced cataract in mice: possible involvement of Ca2+ release and
      calpain activation.
AB  - N-acetyl-p-benzoquinone imine (NAPQI), a semiquinone metabolite of acetaminophen,
      produces cataract in mice. Naphthalene is biotransformed to the cataractogenic
      metabolite 1,2-naphthoquinone (NQ). Intracameral injection of NAPQI elicits a
      rapid increase in free intracellular Ca2+ in the lens epithelium and calpain
      activation before lens opacification begins. In order to test whether the
      cellular response is a common feature of quinone-induced cataracts, we injected
      in this work 1,2-naphthoquinone (NA) in the anterior chamber of mouse eye and
      followed cellular responses in the lens prior to opacity development. A marked
      rise in free intracellular Ca2+ in the lens epithelium and concurrent activation
      of calpain were observed within 1 hr after NQ injection preceding lens opacity
      development. These results support the suggestion that Ca2+ release and calpain
      activation are involved in the mechanism of quinone-induced cataractogenesis.

PMID- 11572470
TI  - Review: practical issues in intravitreal drug delivery.
AB  - The delivery of drugs to the retina from solution or from prolonged release forms
      is considered in terms of pharmacokinetics, interference with vision, and
      toxicity and safety. It is concluded that visual loss will be the limiting factor
      in determining the useful life of a drug administered as a microdispersion.
      Because microparticles can be lost from the vitreous by diffusion, a condensed
      depot of drug can give a greater lifetime. However, it needs to be anchored
      outside the visual pathway which requires an intraocular operative procedure.
      Attaching a reservoir to the external sclera with a diffusion-controlled entry
      through a tube to the vitreous is suggested as having more flexibility than other
      systems.

PMID- 11572471
TI  - Electrical injury and lightning injury: a review of their mechanisms and
      neuropsychological, psychiatric, and neurological sequelae.
AB  - Exposure to electrical current via industrial or residential accidents or
      lightning strikes is a serious and growing concern in today's medical community.
      The sequelae that result are referred to as electrical injury (EI) or lightning
      injury (LI). The relevant principles in electricity are reviewed with particular
      attention given to their damaging capabilities on the body. Specific
      neuropsychological, psychiatric, and neurological signs and symptoms as well as
      objective measures of psychological and neuropsychological functioning and brain
      imaging in victims of EI and LI, are reviewed from past research. Important
      issues relevant to researchers in the field are discussed. Finally, the role that
      neuropsychology might play in this area is outlined.

PMID- 11572472
TI  - Mild traumatic brain injury in sports: neuropsychology's contribution to a
      developing field.
AB  - Mild traumatic brain injuries are common at all levels of athletic competition.
      Although once considered a "routine part of the game," a significant amount of
      attention has recently been placed on these injuries at the professional,
      college, and high school levels. This paper reviews the epidemiology of sports
      related brain injuries, the pathophysiology of the injuries, and the role of
      neuropsychology in this newly emerging area. Issues related to the adequacy of
      neuropsychological test instruments and approaches are discussed in light of
      future directions for research.

PMID- 11572473
TI  - MicroCog: assessment of cognitive functioning.
AB  - MicroCog: Assessment of Cognitive Functioning version 2.1 (Powell, D. H., Kaplan,
      E. F., Whitla, D., Catlin, R., and Funkenstein, H. H. (1993). The Psychological
      corporation, San Antonio, TX.) is one of the first computerized assessment
      batteries commercially developed to detect early signs of cognitive impairment.
      This paper reviews its psychometric characteristics and relates them to its
      clinical utility. It concludes that MicroCog provides an accurate, cost-effective
      screen for early dementia among elderly subjects living in the community and that
      it can distinguish dementia from depression. Its ability to detect cognitive
      decline at other ages or to discriminate dementia from other mental disorders has
      not been established. MicroCog measures different constructs than do traditional
      neuropsychological tests, making it difficult to relate test performance to
      current models of cognitive functioning. The review recommends further
      development of MicroCog and discusses its implications for the future of computer
      based neuropsychological assessment.

PMID- 11572474
TI  - The role of p38 MAP kinase in hydrogen peroxide mediated endothelial solute
      permeability.
AB  - OBJECTIVE: The purpose of this study was to determine the contribution of p38 MAP
      kinase activity during hydrogen peroxide mediated increased endothelial solute
      permeability. We also sought to identify the role of p38 MAP kinase-mediated
      changes in endothelial cell architecture due to hydrogen peroxide challenge.
      METHODS: Hydrogen peroxide mediated permeability of HUVEC was determined with and
      without inhibition of p38 MAP kinase by SB202190. Hydrogen peroxide mediated
      rearrangement of the endothelial actin cytoskeleton and junctional proteins
      occludin and ZO-1 were observed by immunofluorescence microscopy. RESULTS:
      Hydrogen peroxide treatment of endothelial monolayers caused a significant
      increase in solute permeability over a ninety-minute time period. Oxidant
      mediated permeability and phosphorylation of p38 MAP kinase was significantly
      attenuated by SB 202190. Immunofluorescent staining for the tight junctional
      proteins occludin and ZO-1 demonstrated that oxidant challenge caused a loss of
      endothelial tight junction organization. Rhodamine phalloidin staining of the
      actin cytoskeleton showed that hydrogen peroxide stimulated increased stress
      fiber formation with concomitant gap formation between adjacent endothelial
      cells. Inhibition of p38 MAP kinase during oxidant challenge significantly
      attenuated actin stress fiber formation and prevented gap formation. CONCLUSIONS:
      These data demonstrate that p38 MAP kinase activity is involved in hydrogen
      peroxide mediated permeability, stress fiber formation, and intracellular gap
      formation.

PMID- 11572475
TI  - Gender-related differences in proliferative responses of vascular smooth muscle
      cells to endothelin-1.
AB  - Endothelin-1 is an endothelium-derived factor which alters tone and proliferation
      of vascular smooth muscle and has been implicated in the development of
      atherosclerosis. Estrogen modulates production of and contractile responses to
      endothelin-1. Since atherosclerosis is less in estrogen-replete women compared to
      men, experiments were designed to determine whether or not there were gender
      associated differences in proliferative responses to endothelin-1 and effect of
      estrogen status on those responses. Proliferation of smooth muscle cells derived
      from coronary arteries of sexually mature, gondally intact male and female and
      oophorectomized female pigs was determined by thymidine incorporation in the
      absence and presence of endothelin-1 with and without 17beta-estradiol.
      Endothelin-1 (10(-9) M to 10(-7) M) significantly inhibited proliferation only in
      coronary smooth muscle cells from intact female pigs. Addition of beta-estradiol
      inhibited proliferation of cells from intact females but there was not a
      synergistic effect with endothelin-1. Gender associated inhibition of smooth
      muscle proliferation by endothelin-1 may contribute, in part, to cardioprotection
      noted in estrogen-replete states.

PMID- 11572476
TI  - Exercise in sickle cell anemia: effect on inflammatory and vasoactive mediators.
AB  - The aim of this study was to determine the response of inflammatory and
      vasoactive mediators to 3 consecutive days of exercise in African-American women
      with and without sickle cell anemia (SCA). Circulating inflammatory mediators [C
      reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha
      (TNFalpha)] were measured before, and vasoactive mediators [endothelin-1 (ET-1),
      nitric oxide metabolites (NOx)] before and after each exercise bout in ten
      subjects with SCA and ten controls. Exercise did not affect ET-1, IL-6 or CRP
      concentrations (p >.05). TNFalpha was higher in SCA than controls (p < or =
      .0005) at all times; however, the response pattern was similar for the groups: no
      change from day 1 to day 2, but a decrease from day 2 to day 3 (p < or = .05).
      NOx increased significantly after exercise (p < or = .0001) but returned to
      baseline by 24 h afterward. On the 3rd day, NOx increased after exercise in SCA
      but not in the controls (p < or = .05). In conclusion, exercise did not cause a
      harmful inflammatory response in these individuals with SCA. However, NOx
      increased after exercise on all 3 days in SCA but appeared attenuated after 2
      days in controls.

PMID- 11572477
TI  - Colombian study to assess the use of noninvasive determination of endothelium
      mediated vasodilatation (CANDEV). Normal values and factors associated.
AB  - The endothelium plays a critical role in vascular homeostasis. Recently, a
      noninvasive method has been developed to assess flow mediated vasodilatation of
      the brachial artery (FMD). This test is remarkably stable overtime but no clear
      set of normal values has been developed. The purposes of our study were to
      evaluate the accuracy and reproducibility and to identify a set of normal values
      of FMD. We included 253 normotensive healthy volunteers from three Colombian
      cities (mean age: 38.2 years; 33% were women). All subjects underwent ultrasound
      evaluation of endothelial and smooth muscle function. Flow mediated vessel
      diameter change was measured by two independent observers. The interobserver
      Lin's concordance correlation coefficient was 0.88% (95% CI: 0.82, 0.94) and
      there was no evidence of systematic difference between the two measurements (mean
      difference of -0.30% with limits of agreement of -4.48 to 3.87). Mean %FMD was
      11.98% (95% CI: 11.36, 12.61), 13.32% (95% CI: 12.39, 14.25) in women and 11.32%
      (95% CI: 10.52, 12.13) in men. Subjects with no cardiovascular risk factors had a
      mean %FMD of 13.74% (95% CI: 13.14, 14.35), in contrast to a mean of only 7.40%
      (95% CI: 4.33, 9.91) in those with at least one risk factor. A %FMD cut point of
      10.4 had a sensitivity of 71.2% and an specificity of 77.2% to identify subjects
      with at least one cardiovascular risk factor. Using this cut point, endothelial
      dysfunction was 3.13 times more frequent in subjects with than in subjects
      without cardiovascular risk factors (95% CI: 2.30, 4.25). In addition, obesity,
      smoking and hypercholesterolemia were the modifiable risk factors with largest
      independent significant reduction effects on %FMD. FMD measurements can be made
      with high accuracy and precision, and a cut point of 10.4% is useful to
      discriminate between subjects with and without cardiovascular risk factors, and
      can be recommended as a screening test for the detection of patients at risk of
      CVD.

PMID- 11572478
TI  - Update on pulmonary edema: the role and regulation of endothelial barrier
      function.
AB  - Discovery of the pathophysiologic mechanisms leading to pulmonary edema and
      identification of effective strategies for prevention remain significant clinical
      concerns. Endothelial barrier function is a key component for maintenance of the
      integrity of the vascular boundary in the lung, particularly since the gas
      exchange surface area of the alveolar-capillary membrane is large. This review is
      focused on new insights in the pulmonary endothelial response to injury and
      recovery, reversible activation by edemagenic agents, and the
      biochemical/structural basis for regulation of endothelial barrier function. This
      information is discussed in the context of fundamental concepts of lung fluid
      balance and pulmonary function.

PMID- 11572479
TI  - Complete genome sequence of an aerobic thermoacidophilic crenarchaeon, Sulfolobus
      tokodaii strain7.
AB  - The complete genomic sequence of an aerobic thermoacidophilic crenarchaeon,
      Sulfolobus tokodaii strain7 which optimally grows at 80 degrees C, at low pH, and
      under aerobic conditions, has been determined by the whole genome shotgun method
      with slight modifications. The genomic size was 2,694,756 bp long and the G + C
      content was 32.8%. The following RNA-coding genes were identified: a single 16S
      23S rRNA cluster, one 5S rRNA gene and 46 tRNA genes (including 24 intron
      containing tRNA genes). The repetitive sequences identified were SR-type
      repetitive sequences, long dispersed-type repetitive sequences and Tn-like
      repetitive elements. The genome contained 2826 potential protein-coding regions
      (open reading frames, ORFs). By similarity search against public databases, 911
      (32.2%) ORFs were related to functional assigned genes, 921 (32.6%) were related
      to conserved ORFs of unknown function, 145 (5.1%) contained some motifs, and
      remaining 849 (30.0%) did not show any significant similarity to the registered
      sequences. The ORFs with functional assignments included the candidate genes
      involved in sulfide metabolism, the TCA cycle and the respiratory chain. Sequence
      comparison provided evidence suggesting the integration of plasmid, rearrangement
      of genomic structure, and duplication of genomic regions that may be responsible
      for the larger genomic size of the S. tokodaii strain7 genome. The genome
      contained eukaryote-type genes which were not identified in other archaea and
      lacked the CCA sequence in the tRNA genes. The result suggests that this strain
      is closer to eukaryotes among the archaea strains so far sequenced. The data
      presented in this paper are also available on the internet homepage
      (http://www.bio.nite.go.jp/E-home/genome_list-e.html/).

PMID- 11572480
TI  - Genome analysis of Agrobacterium tumefaciens: construction of physical maps for
      linear and circular chromosomal DNAs, determination of copy number ratio and
      mapping of chromosomal virulence genes.
AB  - The phytopathogenic bacterium Agrobacterium tumefaciens is unique in that it
      possesses both linear and circular DNA chromosomes in addition to a plant-tumor
      inducing (Ti) plasmid. We analyzed the two chromosomal DNA molecules in strain
      MAFF301001, whose Ti plasmid has already been sequenced completely. Physical maps
      of the chromosomal DNAs were constructed by Southern hybridization experiments
      using Pme I and Swa I fragments and short fragments bridging the Swa I fragments
      with special care to avoid any missing fragment. Hybridization with 16S rDNA
      probe showed one rDNA locus on the linear chromosome and two loci on the circular
      chromosome. For this bacterium to be pathogenic, not only Ti plasmid but also
      chromosomal genes are required. The chromosomal virulence (chv) genes (chvA,
      chvB, chvD, chvE, chvG, chvH, and chvI) and the chromosomal genes affecting the
      virulence [acvB, pgm(exoC), glgP, miaA, and ros] were successfully mapped onto 5
      different regions in the chromosomal physical maps. These chv genes and the
      chromosomal genes affecting the virulence other than pgm and glgP were found on
      the circular chromosome, whereas the pgm and glgP genes were located on the
      linear chromosome. In contrast to the large terminal inverted repeats of
      Streptomyces linear chromosomal DNA, no hybridization signal was detected between
      left and right terminal fragments of the linear A. tumefaciens chromosome.
      Quantitative analysis of DNA fragments indicated that the copy numbers of the two
      chromosomal DNAs and the Ti plasmid are identical.

PMID- 11572481
TI  - Monitoring of methyl jasmonate-responsive genes in Arabidopsis by cDNA
      macroarray: self-activation of jasmonic acid biosynthesis and crosstalk with
      other phytohormone signaling pathways.
AB  - Jasmonates mediate various physiological events in plant cells such as defense
      responses, flowering, and senescence through intracellular and intercellular
      signaling pathways, and the expression of a large number of genes appears to be
      regulated by jasmonates. In order to obtain information on the regulatory network
      of jasmonate-responsive genes (JRGs) in Arabidopsis thaliana (Arabidopsis), we
      screened 2880 cDNA clones for jasmonate responsiveness by a cDNA macroarray
      procedure. Since many of the JRGs reported so far have been identified in leaf
      tissues, the cDNA clones used were chosen from a non-redundant EST library that
      was prepared from above-ground organs. Hybridization to the filters was achieved
      using alpha-33P-labeled single-strand DNAs synthesized from mRNAs obtained from
      methyl jasmonate (MeJA)-treated and untreated Arabidopsis seedlings. Data
      analysis identified 41 JRGs whose mRNA levels were changed by more than three
      fold in response to MeJA. This was confirmed by Northern blot analysis by using
      eight representatives. Among the 41 JRGs identified, 5 genes were JA biosynthesis
      genes and 3 genes were involved in other signaling pathways (ethylene, auxin, and
      salicylic acid). These results suggest the existence of a positive feedback
      regulatory system for JA biosynthesis and the possibility of crosstalk between JA
      signaling and other signaling pathways.

PMID- 11572482
TI  - Mapping of quantitative trait locus related to submergence tolerance in rice with
      aid of chromosome walking.
AB  - The major QTL for submergence tolerance was locate in the 5.9 cM interval between
      flanking RFLP markers. To narrow down this region, a physical map was constructed
      using YAC and BAC clones. A 400-kb YAC was identified in this region and later
      its end fragments were used to screen a rice BAC library. Through chromosome
      walking, 24 positive BAC clones formed two contigs around linked-RFLP markers,
      R1164 and RZ698. Using one YAC end, six BAC ends and three RFLP markers, a fine
      scale map was constructed of the 6.8-cM interval of S10709-RZ698 on rice
      chromosome 9. The submergence tolerance and related trait were located in a
      small, well-defined region around BAC-end marker 180D1R and RFLP marker R1164.
      The physical-to-map distance ratio in this region is as small as 172.5 kb/cM,
      showing that this region is a hot spot for recombination in the rice genome.

PMID- 11572483
TI  - Allele-specific X-linked gene activity in normal human cells assayed by expressed
      single nucleotide polymorphisms (cSNPs).
AB  - In mammals, dosage compensation at X-linked loci is achieved by the process of X
      chromosome inactivation in the homogametic sex. While most genes on the inactive
      X chromosome (Xi) are subjected to transcriptional inactivation, some escape
      inactivation and present biallelic expression. The expression status of X-linked
      genes has been extensively studied in somatic cell hybrids containing only the
      human Xi. Although this approach has recently been used to generate a profile of
      X-linked gene activity, it may not reflect what happens in a normal human cell.
      The recent development of a database of single nucleotide polymorphisms (SNPs)
      throughout the human genome enables investigation of allele-specific gene
      expression in normal human cells. In this study, we established a panel of X
      linked expressed SNPs (cSNPs). These markers were used for monitoring gene
      expression in primary human fibroblast cell lines with completely skewed XCI,
      demonstrating the potential of this system for studying X-linked gene expression
      in normal human cells.

PMID- 11572484
TI  - Prediction of the coding sequences of unidentified human genes. XXI. The complete
      sequences of 60 new cDNA clones from brain which code for large proteins.
AB  - As an extension of a sequencing project of human cDNA clones which encode large
      proteins of unidentified genes, we herein present the entire sequences of 60 cDNA
      clones for the genes named KIAA1879-KIAA1938. The cDNA clones were isolated from
      size-fractionated cDNA libraries derived from human fetal brain, adult whole
      brain and amygdala, and their protein-coding sequences were predicted. Thirty
      seven cDNA clones entirely sequenced in this study were selected as cDNAs which
      have coding potentiality by in vitro transcription/translation experiments, and
      the remaining 23 cDNA clones were chosen by computer-assisted analysis of
      terminal sequences of cDNAs. The average sizes of the inserts and corresponding
      open reading frames of cDNA clones analyzed here were 4.5 kb and 2.2 kb (733
      amino acid residues), respectively. Sequence analyses against the public
      databases enabled us to annotate the functions of the predicted products of the
      25 genes; 84% of these predicted gene products (21 gene products) were classified
      into proteins related to cell signaling/communication, nucleic acid management,
      and cell structure/motility. In addition to the sequence information about these
      60 genes, their expression profiles were also studied in some human tissues
      including brain regions by reverse transcription-coupled polymerase chain
      reaction, products of which were quantified by enzyme-linked immunosorbent assay.

PMID- 11572485
TI  - Arabidopsis cDNA clones isolated by transcomplementation of the fission yeast
      cAMP phosphodiesterase mutant.

PMID- 11572486
TI  - Challenges to pediatric dentists.

PMID- 11572487
TI  - A 20-year perspective on the changing use of hand over mouth (HOM) and restraint
      in postdoctoral pediatric dental education.
AB  - PURPOSE: This study assessed the current teaching and utilization of the hand
      over mouth technique in advanced educational programs in pediatric dentistry and
      compared these results to previous surveys. METHODS: A survey, identical to those
      used in 1979 and 1989, was sent to pediatric dentistry program directors.
      Descriptive and comparative statistics evaluated the use of HOM, HOMAR, and
      restraint. Additionally, changing patterns of responses for programs and
      directors that responded to both the 1989 and 1999 surveys were assessed.
      RESULTS: Eighty-seven percent of directors returned surveys. There was a
      significant decrease in the number of programs utilizing the HOM technique in the
      past 10 years (P< 0.0001). Among respondents that returned surveys in 1989 and
      1999, 50% of the previous HOM users discontinued its use (P<0.03). Technique non
      users were significantly less likely to describe the technique consistent with
      AAPD guidelines (P<O.0001). Although the 1989 respondents expressed significantly
      decreased certainty that restraint techniques were free of psychological
      sequealae compared to 1979 respondents, the continuing decreasing trend observed
      between the 1989 and 1999 groups was not significant. CONCLUSIONS: With
      continuing uncertainty regarding psychological sequealae associated with HOM,
      there was a significant decrease in the number of programs advocating its use.

PMID- 11572488
TI  - Conscious sedation experiences in graduate pediatric dentistry programs.
AB  - PURPOSE: Conscious sedation is a behavior modification adjunct taught in all
      postgraduate pediatric dental residency programs. It has been a decade since the
      last survey was done specifically related to didactic and clinical aspects of
      conscious sedation in postgraduate pediatric dental programs. The aim of the
      study was to determine the clinical and didactic experiences associated with
      conscious sedation in these programs and to compare some of the findings to those
      collected a decade ago. METHODS: A 31-item survey similar to that of a decade ago
      was constructed and sent to all pediatric dentistry program directors of
      accredited postgraduate and residency programs in the United States. The items
      covered several didactics including didactic topics, sedative agents, monitoring,
      and emergency policy among others. A follow-up mailing was done involving those
      who had not responded 6 weeks following the initial mailing. RESULTS: Fifty-four
      of 58 (93%) program directors returned the 31-item survey. The following are
      highlighted findings. Conscious sedation among residency programs was achieved
      most commonly with a combination of sedative agents used with N2O. Midazolam was
      more popular than chloral hydrate. The oral route was the predominant route of
      administration. More lecture hours were spent on conscious sedation than 10 years
      ago. The pre-cordial stethoscope, pulse oximeter, and blood pressure cuff were
      the most commonly used monitors. Sedative agent and anticipated depth of sedation
      were the factors most often considered in choosing monitors used during the
      sedation of a patient. The capnograph was being used more frequently than it was
      10 years ago. Programs did not report an increase in sedation emergencies but
      practiced emergency drills more often and had increased numbers of individuals
      certified in Advanced Cardiac Life Support (ACLS) or Pediatric Advanced Life
      Support (PALS). The percent of the total patient population which required
      sedation is about 1-20%, with most directors reporting an increase in the numbers
      of sedations done in the past few years. CONCLUSIONS: While many factors remained
      unchanged or slightly modified when compared to the survey done a decade ago, the
      results of this study suggest that there has been significant changes in several
      key factors including the most frequently used sedative (i.e., midazolam) and
      increased preparation in the area of emergency preparedness.

PMID- 11572489
TI  - SEM study of a self-etching primer adhesive system used for dentin bonding in
      primary and permanent teeth.
AB  - PURPOSE: The purpose of this study was to evaluate the interfacial
      micromorphology of direct esthetic restorations bonded to primary or permanent
      tooth dentin with a self-etching primer adhesive system. METHODS: Superficial
      dentin at the occlusal surface of 15 primary and 15 permanent molars was exposed
      with a carbide bur. Prompt-L-Pop was applied in one half of each surface. A
      control bonding system, Single Bond or Vitremer Primer, was used in the other
      half Teeth were restored either with a composite resin (Filtek Z250), a compomer
      (Hytac), or a resin-modified glass ionomer (Vitremer). Twenty-five scanning
      electron microscope fields from 5 teeth were evaluated blindly by two
      investigators for each condition. RESULTS: In this study, a significant
      difference in quality of the interfacial seal was not observed when restorations
      performed in primary teeth were compared to restorations in permanent teeth.
      Interfacial gaps were observed in most restorations bonded with Prompt-L-Pop and
      restored with Filtek Z250 (9/10), Hytac (9/10), or Vitremer (5/10). No
      interfacial gaps were observed in teeth bonded with Single Bond and restored with
      Filtek Z250 (0/10) or Hytac (0/10), while all teeth bonded with Vitremer Primer
      and restored with Vitremer presented gaps (10/10). To understand the reason for
      the interfacial gaps observed with Prompt-L-Pop, we examined if this system
      generated a hybrid layer at the dentin/restorative material interface. All
      surfaces bonded with Single Bond and restored with Filtek Z250 or Hytac presented
      a visible hybrid layer. In contrast, 0/10 (Z250) and only 3/10 (Hytac)
      restorations bonded with Prompt-L-Pop showed signs of a hybrid layer. CONCLUSION:
      The self-etching primer adhesive system Prompt-L-Pop failed to generate sealed
      interfaces consistently between the dentin of primary and permanent teeth and the
      composite resin or the compomer evaluated in this study.

PMID- 11572491
TI  - Multifaceted use of ProRoot MTA root canal repair material.
AB  - Mineral Trioxide Aggregate (MTA) is a new material recently approved by the FDA
      for use in pulpal therapy. MTA has been reported to have superior
      biocompatibility and sealing ability and is less cytotoxic than other materials
      currently used in pulpal therapy. This report is a review of MTA's physical and
      biological properties and the clinical techniques of direct pulp capping,
      apexification, and repair of failed calcium hydroxide therapy.

PMID- 11572490
TI  - Parental perceptions of unmet dental need and cost barriers to care for
      developmentally disabled children.
AB  - PURPOSE: The purpose of this investigation was to describe and assess the
      disparities, if any, in parental perceived cost barriers to oral health care
      among developmentally disabled children using a national data set. METHODS: Data
      from the 1997 National Health Interview Survey (NHIS) were analyzed using a
      SUDAAN statistical package. RESULTS: After adjusting for age and sex, parental
      perception of unmet need was significantly associated with developmentally
      disabled children 2-17 years in lower socioeconomic groups. CONCLUSIONS: Though
      most children from lower socioeconomic groups are eligible for Medicaid coverage,
      parents of these children perceive cost barriers to dental care. Children with
      developmental disabilities face even more perceived barriers to care based on
      family income.

PMID- 11572492
TI  - Outcome of formocresol/ZOE sub-base pulpotomies utilizing alternative
      radiographic success criteria.
AB  - PURPOSE: The purposes of this investigation were to 1) measure success of a
      primary tooth pulpotomy technique that applies formocresol in the sub-base
      without the common five-minute application of a formocresol impregnated cotton
      pellet; and 2) compare success rates of the pulpotomy procedure using traditional
      criteria found throughout the literature with new criteria recently established,
      excluding internal resorption as a radiographic failure. METHODS: Clinical and
      radiographic data were collected from a retrospective chart review of patients
      receiving formocresol pulpotomies with the application of formocresol in the zinc
      oxide-eugenol sub-base. RESULTS: Clinical and radiographic data were available
      for 196 primary molars in 122 children (followup=six to 103 months; mean=49
      months). Traditional assessment of radiographic success and failure yielded a
      success rate of 79%. Alternative assessment excluding internal resorption as a
      failure yielded a 99% success rate. Most frequently observed pulpal responses
      were calcific metamorphosis and internal resorption. Overall clinical success was
      99%. Two of the 196 teeth were extracted due to failure. A survival analysis
      demonstrated that the overall probability of survival remained high over time
      with a cumulative survival of over 95% after six years. CONCLUSIONS: The overall
      success rates in this study indicate that the formocresol pulpotomy technique
      incorporating formocresol in the zinc oxide-eugenol sub-base is a very successful
      treatment modality for primary molars requiring pulp therapy.

PMID- 11572494
TI  - More on the year one dental visit.

PMID- 11572493
TI  - Communication strategies used during pediatric dental treatment: a pilot study.
AB  - PURPOSE: Effective verbal communication is essential for successful dental
      treatment. The purpose of this study was to qualitatively and quantitatively
      examine communication techniques used by pediatric postdoctoral students during
      treatment. The operation of a communication model comprised of three linguistic
      approaches-permissive, empathic and personal-together with other strategies
      common to all three, was examined. METHODS: The study group consisted of 24
      children (14 boys and 10 girls), 3 to 12 years of age. All four dentists were 2nd
      year residents in pediatric dentistry. Conversations were taped and analyzed
      linguistically and statistically. The frequency of use of each approach was
      tabulated and correlated to the children's reported anxiety, cooperation during
      treatment, success of treatment, and mood at the end of treatment. RESULTS: All
      dentists used the three approaches; the permissive approach, which supplied
      procedural information, was the most frequently used approach. The empathic
      approach was the least frequently used. Correlation tests showed that the
      empathic approach was most significantly related to the success of the treatment.
      Components of the permissive approach that contributed to the success of
      treatment were sensory information and supplying reasons. CONCLUSIONS: Although
      generalization is limited because of the small sample, improving verbal
      conversational skills, emphasizing certain strategies, and improving linguistic
      abilities will contribute to better communication between child and pediatric
      dentist and to better cooperation and success in treatment.

PMID- 11572496
TI  - Retrospective survey of dental anomalies and pathology detected on maxillary
      occlusal radiographs in children between 3 and 5 years of age.
AB  - PURPOSE: Radiographs play an important role in the diagnosis of anomalies and
      pathology of the oral structures of young children as well as in the interception
      and management of developmental problems in the dentition. The occlusal film,
      commonly indicated in the young child, is a helpful tool in establishing a
      baseline and in revealing certain region-specific dental concerns in a timely
      fashion. The purpose of this retrospective study was to perform a comprehensive
      examination of maxillary occlusal radiographs in a clinical pediatric population
      and to determine the prevalence of dental anomalies and pathology in the
      premaxilla in children between 3 and 5 years of age. METHODS: Radiographs of
      healthy preschool children (236 males and 264 females), who received their
      initial examination at the University of Texas-Houston Pediatric Dentistry
      Graduate Clinic during 1997 and 1998, were reviewed independently by two
      pediatric dentists, using a 2X magnifying lens and a standard dental light box.
      Interexaminer discrepancies were resolved by consultation and mutual agreement.
      RESULTS: Ninety-two (18%) showed no evidence of dental caries, restorations,
      current pathological conditions, or other anomalies. Frequencies of anomalies
      such as congenitally missing and supernumerary teeth were consistent with other
      reports. CONCLUSIONS: These observations emphasize the importance of obtaining
      intraoral radiographs on preschool children who are in apparent good dental
      health.

PMID- 11572495
TI  - Reactions of children to maxillary infiltration and mandibular block injections.
AB  - PURPOSE: The purpose of this study was to assess children's reactions to the
      administration of local anesthetic injection in the mandible and in the maxilla,
      and to study their sensation of pain after each type of injection. METHODS:
      Twenty-six children between the ages of 4 to 6 (mean age 5.3+/-0.7 years), and 34
      children aged between 7 to 10 (mean age 8.1+/-1.1 years,) who were undergoing
      dental treatment in a pediatric dental clinic, were selected for this study. A
      random crossover design was used. Each patient was randomly assigned to receive
      either maxillary infiltration or mandibular block on the first visit, and the
      remaining local anesthesia on the second visit. During the injection, the
      modified Behavioral Pain Scale, was used. It comprised the following parameters:
      a) facial display, b) arm/leg movements, c) torso movements, and d) crying.
      Immediately after administering the local anesthesia, children were asked to rate
      their feeling according to the Facial Affective Scale. RESULTS: The children in
      each group responded positively to both techniques revealing that there was no
      difference in either one. Subjective and objective evaluation disclosed no
      difference when mandibular block was administered during the first or second
      visit. Regarding the objective evaluation, in all parameters, more children
      reacted positively during administration of mandibular block than during
      maxillary infiltration. CONCLUSION: a) mandibular block and maxillary
      infiltration are similarly accepted by children when first administered, and b)
      children may feel inconvenience or pain and react by crying, yet may report a
      positive feeling in general.

PMID- 11572497
TI  - Cementoblastoma associated with a primary tooth: a rare pediatric lesion.
AB  - An intraosseous, slightly painful swelling was noted upon clinical examination of
      an eight-year-old girl. The swelling was of an unspecified duration and slow
      growing in nature. A radiopaque mass with a radiolucent periphery attached to the
      roots of the mandibular right second primary molar was noted on a periapical
      radiograph. The diagnosis of cementoblastoma was verified by the histologic
      assessment.

PMID- 11572498
TI  - Palatal blue nevus in a child.
AB  - The intraoral blue nevus occurs infrequently in children. This case report
      describes the clinical features of an acquired blue nevus in a 7 year-old girl
      that involved the palatal mucosa. A differential diagnosis and justification for
      surgical excision of this oral lesion are discussed.

PMID- 11572499
TI  - "All in a day's work"--the challenges of pediatric dentistry.

PMID- 11572501
TI  - Introduction to a novel extraction forcep.

PMID- 11572500
TI  - Management of avulsed permanent incisors: a decision analysis based on changing
      concepts.

PMID- 11572502
TI  - Treatment of cariously involved fused maxillary primary lateral and central
      incisors.
AB  - A 3-and-a-half-year-old male child presented with fused cariously involved right
      maxillary primary central and lateral incisors as well as a previously
      traumatized non-vital left primary central incisor with a draining fistula. The
      child also had other restorative needs and the decision taken was to address all
      needs under a G.A. With respect to the fused incisors, these were split and root
      canals treatment was performed for all three incisors which were then restored
      with stainless steel crowns with esthetic facings.

PMID- 11572503
TI  - Oral midazolam-grapefruit juice drug interaction.
AB  - Oral midazolam is a frequently used sedative in pediatric dentistry. Although an
      oral form of midazolam is now commercially available, some practitioners continue
      to use the IV midazolam as an oral medication. If the injectible form of
      midazolam is administered orally, its bitter taste requires the use of a
      flavoring agent. Grapefruit juice is contraindicated for this purpose as it
      inhibits cytochrome P450 (CYP) 3A4. CYP 3A4 is located in the intestine and
      liver. Inhibition of this cytochrome results in delayed absorption and reduced
      first pass effect on midazolam. This results in increased blood plasma levels of
      midazolam of 56% and increased midazolam bioavailability of 35%. This can result
      in excessive levels of sedation for the pediatric patient. Grapefruit juice is
      therefore contraindicated for use with oral midazolam.

PMID- 11572504
TI  - The amazing 15-minute crown procedure (!).

PMID- 11572505
TI  - Dentin bonding.

PMID- 11572506
TI  - Maximizing esthetic results in posterior restorations using composite opaquers.
AB  - After removal of caries or a faulty existing restoration in a posterior tooth,
      frequently the pulpal floor is a dark substrate. Composites are translucent by
      nature, and even the more opaque shades transmit nearly 60% of visible light,
      meaning that composites require a certain thickness to maintain their intended
      shade, especially if the underlying substrate is particularly dark. Depending on
      the intensity of the dark substrate, even relatively thick composite restorations
      may not be capable of disguising the discolored dentin underneath. The substrate
      absorbs a significant part of the light that would otherwise reflect toward the
      occlusal surface, and the restoration has a nonvital monochromatic grayish color.
      Opaquers and tints (color modifiers) may be extremely useful to overcome this
      situation. In this study, composite restorations were placed in extracted teeth
      to demonstrate that the final esthetic results rely upon the optical properties
      of the background as well as those of the composite material itself. Preparations
      with simulated dark pulpal floors were restored without the use of opaquers and
      tint modifiers. After tooth hydration, the final shade was recorded with
      photographs. The restoration was removed and a new restoration was placed, but
      this time with a technique involving opaquer and tints. This article compares and
      discusses the outcomes of these two procedures. CLINICAL SIGNIFICANCE: This
      demonstration shows a simple technique that can help dentists obtain predictable
      esthetic results in their daily practice with posterior composite restorations.

PMID- 11572507
TI  - Fabrication of direct fiber-reinforced posts: a structural design concept.
AB  - As the clinician continues the quest for optimal functional and esthetic success
      of a tooth-restorative complex, the current selection of restorative materials
      and techniques may prove overwhelming. Although no single system provides the
      ideal restorative solution for every clinical circumstance, understanding of
      general design criteria and the components for the various post and core systems
      available allow the clinician to appropriately select the method and materials
      compatible with the existing tooth structure and desired result. This article
      provides a discussion of the various post and core systems, the methods and
      materials inherent in these systems, and general design principles. Using that
      basic information and clinical experience, the authors offer an alternative
      procedure for the rehabilitation of the intraradicular anatomy of the post
      endodontic channel with a direct composite resin--the fiber-reinforced post and
      core system. CLINICAL SIGNIFICANCE: Using improved restorative materials that
      stimulate the physical properties and other characteristics of natural teeth in
      combination with the proper design principles, the clinician can develop a tooth
      restorative complex with optimal functional and esthetic results.

PMID- 11572508
TI  - Esthetic considerations in removable prosthodontics.
AB  - Patients requiring extensive replacement of teeth with removable prostheses are
      indeed esthetic orphans in many contemporary dental practices. Although the
      advent of successful osseointegration has dramatically reduced the need for
      removable prostheses, there are still many patients who for health, anatomic,
      psychological, or financial reasons are not candidates for implants. These
      patients deserve the same level of esthetic restorative dentistry as those who
      are restored with fixed prostheses. Clearly, the restorative dentist has the
      greatest flexibility from an esthetic standpoint with complete dentures. Soft and
      hard tissues can be replaced with contemporary characterized denture-base
      materials, and a truly infinite variety of tooth forms, shades, and arrangements
      can be used to meet the expectations of the most demanding patient. For partially
      edentulous patients, the major problem is designing a removable partial denture
      that avoids the unsightly display associated with conventional clasp assemblies.
      There are strategies available to accomplish this effectively while establishing
      an environment for optimal periodontal health, and to minimize destructive
      stresses on the abutment teeth. CLINICAL SIGNIFICANCE: This article discusses the
      procedures essential for providing an upscale, quality esthetic service with
      removable prostheses. Effective strategies to eliminate unsightly clasp
      assemblies with removable partial dentures are described.

PMID- 11572509
TI  - Dental color standards: shade tab arrangement.
AB  - PURPOSE: The aim of this study was to analyze the shade tab arrangement of two
      popular dental shade guides, suggest possible improvements, and propose clinical
      guidelines. MATERIALS AND METHODS: Data were recorded using a colorimeter set to
      standard illuminant source C and CIE L*a*b* system. The manufacturers' shade tab
      arrangement as well as the possible improvements in the arrangement of shade tabs
      of Vitapan Classical and Vitapan 3-D Master (Vita Zahnfabrik, Bad Sackingen,
      Germany) shade guides were examined by regression analysis. RESULTS: Certain
      shortcomings in the manufacturers' arrangement of both color standards were
      observed. The Vitapan 3-D Master arrangement was more consistent, but with a
      decrease in lightness, tab saturation decreased as well in four of its five
      groups. When Vitapan Classical and Vitapan 3-D Master tabs were arranged
      according to deltaE* in relation to the lightest tab, r2 was 0.98 and 0.96,
      respectively. After dividing the total deltaE* range into four equal segments for
      the newly established Vitapan Classical guide, r2 was 0.91, 0.95, 0.68, and 0.94,
      respectively. Corresponding r2 values for Vitapan 3-D Master were 0.96, 0.94,
      0.90, 0.94, and 1.0. CLINICAL SIGNIFICANCE: Total color difference in relation to
      the lightest tab, followed by the tab division into an adequate number of groups,
      is recommended as a possible and universally applicable mode of tab arrangement
      in dental color standards.

PMID- 11572510
TI  - Class II composites: Part I.

PMID- 11572514
TI  - Dental implants.

PMID- 11572515
TI  - Apolipoprotein AI and CIII gene polymorphisms and their association with lipid
      levels in Italian, Greek and Anglo-Irish populations of Australia.
AB  - PRIMARY OBJECTIVE: The apolipoprotein (apo) AI-CIII-AIV gene cluster on
      chromosome 11 has been identified as a candidate region for hyperlipidaemia and
      in particular for hypertriglyceridaemia. Our aim was to detect associations
      between the apo AI and CIII polymorphisms and the plasma lipids, total
      cholesterol, triglycerides, high density lipoprotein (HDL) and low density
      lipoprotein (LDL) cholesterol in normal, healthy, adults from three ethnic groups
      of Australia--Italian, Greek and Anglo-Irish, separately by gender. METHODS AND
      PROCEDURES: The SstI restriction fragment length polymorphisms (RFLP) in the 3'
      untranslated region of the apo CIII gene and the MspI RFLP in the third intron of
      the apo AI gene were scored and the lipid concentrations were ascertained using
      standard methodologies. t-tests were used to compare lipid levels between sexes
      and between populations, and multivariate ANOVA was used to detect if the two
      RFLPs had an effect on any of the lipid concentrations. MAIN OUTCOMES AND
      RESULTS: The two RFLPs exhibit strong linkage disequilibrium in all three
      populations (p < 0.001). There were some significant differences in allele
      frequencies among the populations: the minor S2 allele was more frequent in
      Italians (0.12) than Greeks (0.03) (p = 0.003), and the minor M2 allele was more
      common in Greeks (0.14) than Anglo-Irish (0.05) (p = 0.026). We found no
      significant association between either of the RFLPs and any of the lipid
      concentrations in either sex of all three populations. However, Kruskal-Wallis
      tests detected associations of borderline significance between apo AI MspI
      genotypes and triglycerides (p = 0.04) and between apo AI MspI genotypes and
      cholesterol levels (p = 0.03) in Anglo-Irish females. CONCLUSIONS: Because only
      two statistically significant associations were detected among a number of
      comparisons, our data suggest that the apo AI and CIII polymorphisms play only a
      very limited role in mediating variation in lipid concentrations in these three
      ethnic groups.

PMID- 11572516
TI  - The use of regularity as estimated by approximate entropy to distinguish
      saltatory growth.
AB  - A nonlinear dynamics metric, approximate entropy (ApEn), is investigated as a
      diagnostic method for distinguishing between mathematical models, and the
      underlying mechanistic hypotheses that purport to describe the same time series
      experimental observations. ApEn measures the occurrence of pattern regularity
      within a time series, and is used here to investigate growth patterns in daily
      length growth. The notion investigated is that ApEn distributions for competing
      time series patterns expressed as mathematical formulations can be modelled by
      Monte Carlo and bootstrap methods and compared to the ApEn values for an original
      experimental data series. If the ApEn values for the different models do not
      overlap, then it is expected that ApEn can be utilized to distinguish these
      models and hypotheses, and to provide statistical assessment for the underlying
      biological patterns in experimental data. The conclusion is that the ApEn metric
      is successful as a time series diagnostic tool. It is a model-independent
      statistic that clearly differentiates saltatory growth from slowly varying
      continuous models of growth and serves to further document the saltatory nature
      of growth. This is a unique application of approximate entropy, illustrating the
      broad applicability of ApEn to biological time series, with the specific example
      of discriminating a saltatory growth process in longitudinal growth data. Future
      investigations of regularity in longitudinal time series in human biology with
      ApEn statistics are suggested.

PMID- 11572517
TI  - An insight into recent consanguinity within the Basque area in Spain. Effects of
      autochthony, industrialization and demographic changes.
AB  - BACKGROUND: The importance of studying the genetic kinship of those human groups
      characterized by a deeply rooted ethnicity has traditionally been and still is an
      interesting goal of anthropological and population genetic studies. However, only
      a few surveys have aimed to learn about the impact of industrial development on
      the consanguinity of these populations and even those have concentrated on
      industrialized regions. This approach is worth analysing in Spain, where
      industrialization was late in relation to other western European countries. AIM:
      In this work we analyse the characteristics of inbreeding in Guipuzcoa from 1951
      to 1995. This Basque province underwent industrial and tourist development
      earlier than other Spanish regions. It has the highest density of Basque speakers
      and has always occupied a central position within the map of distribution of the
      Basque language. Guipuzcoa is geographically placed in the core of the Basque
      area. SUDJECTS AND METHODS: Data on consanguineous marriages recorded in the
      province of Guipuzcoa between 1951 and 1995 were taken from Roman Catholic
      dispensations stored in the Diocesan Archives of San Sebastian, the province's
      capital city. Over the whole time period, a total of 1152 consanguineous
      marriages were registered. RESULTS: The high frequencies of first cousin (M22) (F
      = 1/16) and uncle-niece, aunt-nephew (M12) (F = 1/8) consanguineous marriages
      distinguish Guipuzcoa from the rest of Iberian populations. The M22/M33 ratio
      (with M33 being second cousins) has never dropped below 0.67, which represents a
      significant deviation from the expectation value of 0.25. When consanguineous
      marriages are classified according to marriage partner birthplaces interesting
      results emerge. Provincial endogamy shows the highest consanguinity rates (57%)
      and the proportion of M22/M33 is also rather high (0.63). However, a major
      contribution to the consanguinity levels and mean inbreeding coefficient recorded
      in Guipuzcoa over recent decades has been made by immigrant relative groups
      coming from other geographical areas of Spain. In this segment of population the
      observed M22/M33 rates are 1.44. CONCLUSIONS: This study shows again how
      important preferentiality (or avoidance) is in human consanguinity, and also how
      human groups, in spite of being spatially settled in the same territory, present
      differential attitudes for given consanguinity patterns.

PMID- 11572518
TI  - Lung function in older humans: the contribution of body composition, physical
      activity and smoking.
AB  - An allometric model was used to determine the important factors related to the
      decline in forced expiratory volume (FEV1.0) across ages 55-86 years in
      independently living men and women. Measurements were available from a randomized
      sample of 181 men and 203 women residing in London, Ontario, Canada. The effects
      of height, age, sex, adiposity, fat free mass (FFM), grip strength and physical
      activity (PA) on FEV1.0 were assessed using an allometric model to test the
      hypothesis that sex differences in lung function would be due in part to sex
      related differences in the aforementioned variables and would therefore be
      eliminated by our analysis. The following model was linearized and parameters
      were identified using standard multiple regression: FEV1.0 = height(beta1) x
      FFM(beta2) x grip strength(beta3) x PA(beta4) x exp(beta0 + beta5age + beta6sex +
      beta7smoking + beta8%body fat) x epsilon. Results indicate that the amount of FFM
      and heavy intensity physical activity participated in by the elderly may be more
      important in influencing forced expiratory function than previously recognized.
      In addition, results from this study have confirmed the importance of age and
      height in the prediction of FEV1.0 and demonstrated a negative effect of smoking
      on lung function. Individuals with a greater FFM and physical activity level
      tended to be associated with an above average lung function performance. The
      cross-sectional rate of decline in FEV1.0 determined from our model was
      approximately 12% per decade.

PMID- 11572519
TI  - A Bayesian approach to infer geographical origins of migrants through surnames.
AB  - BACKGROUND: Surnames are an easy tool to analyse human genetic structure,
      mobility and evolution. Few studies use surnames to estimate human migration at
      different geographical level. PRIMARY OBJECTIVE: Here we propose the application
      of a Bayesian method to estimate the probability of geographical origin (pgo) of
      migrants in a given area using surnames. METHOD: This method can be applied with
      data recordings when they are available for at least two successive periods and
      in the areas which are the potential sources of emigration. The principle is that
      the new surnames which are arriving during the second period in the area under
      investigation can provide information on their geographical origins. The
      probability of the origin of migrants can easily be estimated iteratively from
      the frequency of surnames by using the Bayes' theorem. RESULTS: This method is
      exemplified using civil birth registers at different geographical scales. The pgo
      of migrants, estimated between two periods (1891-1915 and 1916-1940), (i) from
      French departments to Paris (ii), from these departments to Tarbes, and (iii)
      from counties surrounding Tarbes to Tarbes, are mapped and discussed.

PMID- 11572520
TI  - The genetic structure of English villages: surname diversity changes between 1976
      and 1997.
AB  - OBJECTIVE: To examine the change in the coefficient of relationship by isonymy
      (Ri) over a 21-year period. RESEARCH DESIGN: Ri was calculated from the surnames
      of males in the registers of electors for 15 villages near Oxford in 1976 and
      again in 1997. The within-residence component reflected the number of adult men
      of the same surname resident at the same address while the between-resident
      component of Ri was calculated by counting only one name of any surname at each
      address listed in the registers. RESULTS: Ri tended to decrease during the 21
      year-period in 14 of the 15 villages and the between-resident component of Ri
      also tended to decrease in 14 of the villages. The within-residence component
      decreased in a statistically non-significant proportion (11 of the 15 villages).
      CONCLUSIONS: This study, in keeping with some but not all other surveys, showed
      that there was a tendency for random isonymy to decline in the 20th century. The
      reduction in the between-residence component can be accounted for by migration
      into the villages.

PMID- 11572521
TI  - Socioeconomic status, body size and physical activity of adults on Rarotonga, the
      Cook Islands.
AB  - Much of the secular trend toward increased body size among populations in the
      Pacific Region has been attributed to the processes of economic modernization and
      socioeconomic change. The primary objective of the present analysis was to
      examine the relationships between socioeconomic factors and stature, weight, body
      mass index and physical activity level of adult Cook Islanders living a largely
      modernized lifestyle in the Pacific Region. In a cross-sectional study of
      physical activity, body size and socioeconomic status, a volunteer sample of 345
      Cook Islanders aged 20-65 years was obtained from the total adult population of
      Rarotonga, and measured at six out-patient clinics. Stature, weight, body mass
      index (BMI), physical activity level and age were calculated by sex and
      occupational category, years of education, island of birth and number of years
      lived on Rarotonga, respectively, using SPSSPC for Windows. Stepwise multiple
      regression was used to examine the relationships between stature, weight, BMI,
      PALweekday (a measure of physical activity level), age and non-linear functions
      of age, and the socioeconomic variables. These analyses indicate that the secular
      trend in stature is a function of the relative level of modernization on
      Rarotonga relative to other Cook Islands, and with level of education. These
      factors associate differently among males and females, the secular trend among
      males appearing to be a general phenomenon in response to lifestyle change
      associated with life on Rarotonga, while among females the trend is a function of
      lifestyle change associated with education and independent of island of origin.
      The trend toward increasing body fatness is also different for males and females.
      Weight declines with age for both men and women, in a linear way for the males,
      but in a non-linear fashion for the females. Body weight is also greater among
      those males in more skilled and professional occupations than among those with
      less-skilled professions. For the women, weight is independent of occupation
      category. Physical activity patterns of modernizing adult Cook Islanders show no
      relationships with socioeconomic variables for the males, but while older women
      are less active, those born on Rarotonga are less active than those born
      elsewhere in the Cook Islands. The number of years spent on Rarotonga shows no
      significant relationships with any of the physical measures, or with physical
      activity level. This is likely to be as much a function of small sample size as a
      lack of effect. Although declines in energy expenditure with increasing age have
      been demonstrated for both males and females in various populations around the
      world, on Rarotonga this holds true for females and not males, indicating that
      physical activity declines with increasing age in modernizing societies do not
      occur in uniform fashion.

PMID- 11572522
TI  - Secular trends in growth among urban Brazilian children of European descent.
AB  - PRIMARY OBJECTIVE: The purpose of this paper is to describe and discuss a
      significant secular trend in stature and weight in an urban Brazilian population.
      METHODOLOGY: Anthropometric measurements of 7878 children and adolescents from
      Sao Paulo, Brazil, obtained in 1997/98 were compared with data from a previous
      study carried out in 1978. Both samples include children of middle-class urban
      families of European ancestry. MAIN OUTCOMES AND RESULTS: Comparisons between the
      two samples reveal strong positive secular trends in both height and weight.
      Furthermore, the 1997/98 sample shows no growth deficits in relation to the
      WHO/NCHS international reference. CONCLUSIONS: The positive trend can be
      explained as the result of economic development and improvement of social
      indicators, while the absence of growth deficits, contrary to what is reported in
      other studies carried out in developing countries, follows from the common
      genetic background of the Brazilian sample surveyed here and the US sample which
      is the basis of the NCHS/WHO reference.

PMID- 11572523
TI  - Evolution of consanguinity in the Bishopric of Lugo (Spain) from 1900 to 1979.
AB  - BACKGROUND: The levels of consanguinity in human populations are known to be
      influenced by demographic and geographical factors, and by socio-cultural customs
      that govern spouse choice. Within the general model applicable to the populations
      of Western Europe, Galicia (north-west Spain) is a region that is especially
      interesting, due to its geographical and historical peculiarities that could have
      conditioned its behaviour pattern with respect to consanguinity. PRIMARY
      OBJECTIVE: The object of this paper is to analyse the evolution of the
      consanguinity structure levels in the rural population of the Bishopric of Lugo
      (Galicia) during the period 1900-1979. SUBJECTS AND METHODS: The study covers a
      total of 752 parishes included in 52 municipalities of the rural area of the
      Bishopric of Lugo. Of a total of 117,583 marriages in the period studied, 6701
      were between biologically related individuals up to the level of second cousins.
      The percentage of the different types of consanguineous marriages, the
      consanguinity rates, and the average coefficient of inbreeding of the population
      was calculated. Also, for the analysis of the temporal variation of
      consanguinity, version 3.01 of Jandel Scientific's Table Curve program was used.
      MAIN OUTCOMES AND RESULTS: The consanguinity rate for the whole of the period is
      5.70% and the average coefficient of inbreeding is 2.2477 x 10(-3), values which
      fall within the observed range for Spanish populations. As for the consanguinity
      structure, the most frequent types of consanguineous marriages are between second
      cousins (2.65% of all marriages), but the high proportion of marriages between
      uncles/nieces or aunts/nephews (0.16%) and first cousins (2.12%) with regard to
      the total number of marriages should be emphasized. The average value of the
      M22/M33 ratio is 0.80, and throughout the study period it was above the 0.25
      expected in conditions of panmixia. Regarding the evolution of the average
      coefficient of inbreeding, its annual values fit a polynomial regression curve
      with one ascending and one descending branch and an inflection point in the year
      1919. CONCLUSIONS: As in other rural areas of Galicia, the structure of
      consanguinity in the Bishopric of Lugo is characterized by the high proportion of
      marriages between uncles/nieces or aunts/nephews and first cousins, a phenomenon
      which appears to be generalized in the rural populations of northern Spain. It is
      suggested that the high proportion of uncle/niece marriages that have been found
      in the population studied are very probably due to the important migratory
      phenomenon which took place in this region at the end of the 19th century and in
      the first third of the 20th century.

PMID- 11572525
TI  - Team up and write it up.

PMID- 11572524
TI  - Metacarpophalangeal pattern profile analysis of a sample drawn from a North Wales
      population.
AB  - Sexual dimorphism and population differences were investigated using
      metacarpophalangeal pattern profile (MCPP) analysis. Although it is an
      anthropometric technique, MCPP analysis is more frequently used in genetic
      syndrome analysis and has been under-used in the study of human groups. The
      present analysis used a series of hand radiographs from Gwynedd, North Wales, to
      make comparisons, first, between the sexes within the sample and then with
      previously reported data from Japan. The Welsh sexes showed MCPP analyses that
      indicated size and shape differences but certain similarities in shape were also
      evident. Differences with the Japanese data were more marked. MCPP analysis is a
      potentially useful anthropometric technique but requires further statistical
      development.

PMID- 11572526
TI  - Why girls smoke: a proposed community-based prevention program.
AB  - OBJECTIVES: To review the literature on reasons teenage girls start smoking and
      to identify the role and opportunities for nurses to have an impact on this
      public health problem. In addition, a proposed smoking prevention program
      targeted to teenage girls is presented. DATA SOURCES: Information was gathered
      from professional journals and texts and from MEDLINE and PROQUEST. Keywords used
      in the searches were smoking prevention, tobacco use, smoking and adolescents,
      teenage girls and smoking, health education and smoking, and smoking prevention
      programs. DATA SYNTHESIS AND CONCLUSIONS: Smoking initiation in teenage girls is
      a problem with ramifications for individual health as well as for public health.
      Although the literature demonstrates the rising incidence of smoking in teenage
      girls and evidence suggests the reasons girls start smoking differ from those of
      their male counterparts, a dearth of information on smoking prevention programs
      exists for this population. It is reasonable to assume that the best practices
      for adolescent smoking prevention can be applied to programs specifically for
      girls, along with efforts to address social influences, self-image, and self
      esteem, which may be particularly important to teenage girls. The theory of
      reasoned action provides a framework for prevention strategies that target the
      behavioral beliefs and attitudes that influence teenage girls to smoke. Nurses
      can educate themselves about contributing factors that lead teenage girls to
      start smoking. Implementing this knowledge into nursing practice in a variety of
      settings could help meet the Healthy People 2010 goals of reducing teenage
      smoking to 16%.

PMID- 11572527
TI  - Symptom experience in women after hysterectomy.
AB  - OBJECTIVE: To review the literature addressing the symptom experience of women
      after hysterectomy. DATA SOURCES: Computerized searches in MEDLINE and CINAHL, as
      well as texts and references cited in articles. Key concepts in the searches
      included hysterectomy, sleep disturbance and pain, hysterectomy and fatigue,
      hysterectomy, depression, and depressed mood. STUDY SELECTION: Articles and
      comprehensive works relevant to key concepts and published after 1970, with an
      emphasis on new findings from 1990 to 2000. Sixty-four citations were identified
      as useful to this review. DATA EXTRACTION: Data were organized under the
      following headings: women and hysterectomy, biopsychosocial perspectives, common
      symptoms after hysterectomy (pain, disturbed sleep, fatigue, depressed mood,
      anxiety), and significance of review (implications). DATA SYNTHESIS: Literature
      suggests that after a hysterectomy, women experience complications during the
      postoperative recovery period that may vary with the type of surgical procedure.
      During this period, the quantity and quality of sleep as well as other symptoms
      (pain, fatigue, anxiety, and depression) are influenced by various physiologic,
      psychologic, and social factors. Despite limited evidence that sleep problems may
      occur frequently during the recovery period, only a few researchers have
      systematically examined sleep patterns in women after hysterectomy. None of these
      studies, however, used objective sleep measures or examined multiple dimensions
      of these women's lives. CONCLUSIONS: This review conceptualized the women's
      symptom experience as the experience of specific symptoms (pain, sleep
      disturbance, fatigue, depressed mood, and anxiety) that were influenced by
      biopsychosocial factors.

PMID- 11572528
TI  - Social influences on the sexual behaviors of adolescent girls in at-risk
      circumstances.
AB  - OBJECTIVE: To describe social influences on girls' sexual behaviors. DESIGN:
      Descriptive, exploratory study using interviews with five focus groups.
      SETTING/PARTICIPANTS: 48 adolescent girls, ages 12 to 16 years, who were confined
      in a juvenile detention center for a variety of charges. INTERVENTIONS: None.
      MAIN OUTCOME MEASURES: Girls' perceptions of influences on their sexual
      behaviors. RESULTS: The analysis revealed three themes: the influence of
      traditional gender roles, a lack of power in heterosexual relationships, and an
      ongoing search for romance. CONCLUSIONS: The social context of adolescent girls'
      lives can promote sexual activity and unprotected sex. Effective prevention
      efforts must acknowledge the context within which sexual risk occurs and address
      motivations and barriers in the target population.

PMID- 11572529
TI  - Anxiety in Japanese women after elective abortion.
AB  - OBJECTIVE: To examine women's anxiety levels after elective abortion. DESIGN AND
      SETTING: Women seeking elective abortion at six clinics in Japan were solicited
      to participate in a questionnaire survey. PARTICIPANTS: Sixty-six Japanese women
      requesting abortion participated in this survey. MAIN OUTCOME MEASURES: State
      anxiety was measured using Spielberger's State Trait Anxiety Inventory before and
      after abortion. RESULTS: Multiple regression analyses using predictor variables
      with a significant link to postabortion anxiety level showed that among potential
      predictors, a conservative attitude toward abortion was the most significant
      predictor of postabortion anxiety after controlling for the level of preabortion
      anxiety. CONCLUSION: These findings suggest that a woman's attitude toward
      abortion and reproductive rights is an important but neglected factor influencing
      postelective abortion anxiety. Medical and nursing professionals should,
      therefore, take note of a woman's attitude toward abortion as a part of her
      mental health care.

PMID- 11572530
TI  - Heading toward the new normal: a contemporary postpartum experience.
AB  - OBJECTIVE: To describe contemporary women's postpartum experience. Previous
      descriptions, especially Rubin's taking-in and taking-hold, may no longer apply
      in this era of 24- to 48-hour hospital stays. DESIGN: Qualitative descriptive,
      using grounded theory methodology. Participants were interviewed about their
      postpartum experiences. Constant comparative analysis of the interview
      transcripts was concurrent with data collection. SETTING: Interviews were
      conducted in participants' homes during the 1st week after childbirth and again 1
      to 2 weeks later. PARTICIPANTS: Thirty-two first-time mothers, who vaginally
      delivered a full-term infant, were recruited through childbirth education
      classes. RESULTS: The major theme that emerged was Heading toward the new normal,
      a process through which the participants began to reorient their lives as
      mothers. The supporting categories were Appreciating the body, Settling in, and
      Establishing a new family. CONCLUSIONS: The participants' postpartum psychosocial
      development was a continuous process without discrete stages and phases. This
      finding differs from Rubin's puerperal change theory. With this new theoretical
      description, nurses can develop more effective care for contemporary child
      bearing women.

PMID- 11572532
TI  - Parenting self-efficacy and perception of insufficient breast milk.
AB  - OBJECTIVE: Insufficient breast milk is a major reason why mothers give up
      breastfeeding and may be related to low levels of maternal confidence. This study
      explored the relationship between parenting self-efficacy (PES) and perception of
      insufficient breast milk. DESIGN: Cross-sectional descriptive correlational
      study. SETTING: Four private primary care pediatric practices in the northern
      United States. PARTICIPANTS: Sixty breastfeeding mothers of infants ages 1 to 11
      weeks. PROCEDURES: Mothers were recruited during well-baby pediatric visits. They
      returned completed questionnaires by mail. Data were analyzed using descriptive
      statistics, t tests, and multiple regression analysis. MAIN OUTCOME MEASURE: The
      Perception of Insufficient Milk (PIM) questionnaire, an investigator-developed
      instrument. RESULTS: There was a significant correlation (r = .487, p < .01)
      between the self-efficacy and perceived insufficient milk scores. Regression
      analysis revealed that 23% of the variance in PIM was explained by PES, after
      maternal age, education, and parity had been taken into account. CONCLUSIONS:
      Although further research is needed to refine the measurement of perceived
      insufficient milk and differentiate breastfeeding self-efficacy from general
      parenting self-efficacy, nursing interventions to enhance self-efficacy may
      improve mothers' confidence in the adequacy of their milk supply.

PMID- 11572531
TI  - Analgesia for circumcision: effects on newborn behavior and mother/infant
      interaction.
AB  - OBJECTIVE: To test the effectiveness of acetaminophen for pain management during
      and after circumcision. DESIGN: A randomized, double-blind, placebo controlled,
      pretest-posttest design. SETTING: Level III nursery at a Midwestern hospital.
      PARTICIPANTS: Sixty full-term newborns, whose mothers had uncomplicated
      pregnancies and vaginal deliveries. INTERVENTIONS: Administration of 10 mg/kg
      acetaminophen or placebo 1 hour before circumcision. MAIN OUTCOME MEASURES:
      Behaviors (clarity of cues and responsiveness) were observed in newborns during a
      feeding interaction, and pain distress (percentage of time crying and heart rate)
      was assessed during and after the circumcision. RESULTS: ANCOVA revealed
      significant group differences in subscales of the NCAFS (Nursing Child Assessment
      Feeding Scale) for newborns, whereas statistically significant differences for
      mothers were found in the sensitivity to cues and social-emotional growth
      fostering scales. A significant increase in heart rate and crying time during the
      circumcision was noted; however, no significant difference was observed between
      groups. At the diaper change after the circumcision, the percentage of cry did
      suggest an effect from the analgesia. CONCLUSIONS: These findings reinforce the
      reciprocal, synchronous nature of mother-infant interactions during the early
      postpartum period and the need for pain control after circumcision to promote
      neonatal comfort and improve mother-infant interaction.

PMID- 11572533
TI  - Eliminating health inequities: national goals and developing programs.
AB  - In the 20th century, infant and maternal mortality declined dramatically and the
      life span and quality of life for women and infants increased. At the end of the
      century, the rate of decline slowed and policy makers began to look for new ways
      to address the problem. A significant challenge now is to eliminate the
      persistent disparities in maternal and infant health among various racial and
      ethnic groups, particularly between black and white women and infants. To improve
      perinatal outcomes, programs are needed that focus on community-based
      interventions that reduce infant mortality across all racial and ethnic groups.
      Two promising programs that are expected to receive additional federal funding
      through the Children's Health Act are the Fetal and Infant Mortality Review
      Program and home visiting programs. Expansion of these programs may provide the
      vehicle to reduce disparities in maternal and infant mortality and morbidity. New
      programs are needed to meet the ambitious goals of Healthy People 2010.

PMID- 11572534
TI  - Leader or left behind: national and international policies related to
      breastfeeding.
AB  - The U.S. and international breastfeeding policies over the past 80 years present
      a pattern of increased protection for women and children that influences
      breastfeeding acceptance. These begin with the Maternity Protection Convention of
      the International Labor Organization in 1919 and continue through the relatively
      recent establishment of the U.S. Breastfeeding Committee. State and U.S. federal
      laws lag well behind international action, and the U.S. record on adopting
      international initiatives is poor. Nurses can play an influential role in
      consciousness raising, policy development, and advocacy for breastfeeding
      support.

PMID- 11572535
TI  - The human genome and public policy: a nursing perspective.
AB  - The Human Genome Project has completed a rough draft of the sequence that
      comprises human DNA. For the first time, the scientific discoveries have been
      conducted in tandem with research exploring the social, legal, and ethical
      implications of the research. Several committees have studied the policy
      implications of the genetics information explosion. The Secretary's Advisory
      Committee on Genetic Testing's report was received by the Secretary of the U.S.
      Department of Health and Human Services in November 2000 and contains
      recommendations for the oversight of genetic testing. Public policy issues that
      affect nursing practice in the area of genetics must be explored by individual
      nurses and professional nursing organizations.

PMID- 11572536
TI  - An activist looks at nursing's role in health policy development.
AB  - Health care delivery systems are evolving and transforming rapidly. Nurses will
      need new leadership and policy skills to meet the challenge of ensuring patient
      care safety and quality health care delivery. Nurses bring a unique perspective
      to health care policy development because of their educational training,
      professional values and ethics, advocacy skills, and experiential background.
      Significant progress has occurred over the years toward advancing nursing's
      presence, role, and influence in the development of health care policy. However,
      more nurses need to learn how to identify issues strategically; work with
      decision makers; understand who holds the power in the workplace, communities,
      state and federal level organizations; and understand who controls the resources
      for health care services. In health care policy development, nurses are essential
      in ensuring quality health care that is accessible and affordable for all women
      and their infants. More nurses need to actively work as leaders in the health
      policy arena.

PMID- 11572537
TI  - Maternal smoking and the risk of congenital birth defects: a cohort study.
AB  - BACKGROUND: The literature linking gestational smoking to congenital defects has
      been very inconsistent. The purpose of this study was to reinvestigate the
      relation between gestational smoking and congenital malformations. METHODS: This
      study was a retrospective cohort (N = 18,016) of live births in the TriHealth
      Hospital system from 1 January 1998 to 31 December 1999. The cohort included
      1,943 mothers who were smokers. Congenital defects were grouped into 22 different
      categories. Multifactorial logistic regression was used to find any association
      between exposure and the possible outcomes. RESULTS: Mothers who smoked were
      significantly younger and had babies of lower birth weight and shorter
      gestational age (P < .05). Of the 22 categories of congenital defects, only
      cardiovascular system abnormalities showed a significant difference (P < .01)
      between the two groups. The remaining 21 categories of congenital defects showed
      no statistical difference. CONCLUSION: Women who smoke during pregnancy have
      infants that are significantly smaller and of shorter gestational age compared
      with mothers who do not smoke. Based on these data and findings from most of the
      available literature, however, gestational smoking is unlikely to cause a large
      increase in congenital birth defects.

PMID- 11572538
TI  - Therapeutic touch in the treatment of carpal tunnel syndrome.
AB  - BACKGROUND: Alternative medical therapies are widely utilized, but there are few
      objective data to evaluate the effectiveness of these techniques. The purpose of
      this study was to determine whether one alternative therapy, Therapeutic Touch
      (TT), can improve objective indices of median nerve function in patients with
      carpal tunnel syndrome. METHODS: Participants with electrodiagnostically
      confirmed carpal tunnel syndrome were randomly assigned in single-blind fashion
      to receive either TT or sham therapeutic touch once weekly for 6 consecutive
      weeks. The distal latency of the median motor nerve along with visual analog
      assessments of pain and relaxation were measured before and after each treatment
      session. RESULTS: Twenty-one participants completed the study. Changes in median
      motor nerve distal latencies, pain scores, and relaxation scores did not differ
      between participants in the TT group and participants in the sham treatment
      group, either immediately after each treatment session or cumulatively.
      Immediately after each treatment session, however, there were improvements from
      baseline among all the outcome variables in both groups. CONCLUSIONS: In this
      small study, TT was no better than placebo in influencing median motor nerve
      distal latencies, pain scores, and relaxation scores. The changes in the outcome
      variables from baseline in both groups suggest a possible physiologic basis for
      the placebo effect.

PMID- 11572539
TI  - Individual and contextual factors related to family practice residents'
      assessment and counseling for tobacco cessation.
AB  - BACKGROUND: Tobacco use is the chief avoidable cause of death in the United
      States. Physicians, however, are not routinely assessing this risk and providing
      counseling for risk reduction. This study examines tobacco cessation counseling
      practices among family practice residents and explores the determinants of
      residents' smoking-counseling behaviors and counseling duration. METHODS: One
      hundred ten family practice residents (response rate = 93.2%) from four Texas
      residency training programs completed a survey designed to assess tobacco
      cessation counseling practices. RESULTS: A high proportion of residents reported
      that they usually or always assessed tobacco use (59.3%) and advised their
      patients to quit smoking (80.9%), with a lower proportion reporting specific
      counseling behaviors (7.3% - 21.9%), referrals (1.8%), or follow-up visits
      (1.8%). Year of residency, perceived effectiveness, and the interaction between
      perceived effectiveness and residency year were significantly associated with
      number of counseling behaviors, and year of residency and perceived effectiveness
      were significantly associated with counseling duration. CONCLUSIONS: Faculty
      physicians should assist residents to implement the Public Health Service
      sponsored clinical practice guideline for tobacco control. There is a need to
      increase behavioral skills and perceived effectiveness for assessing and
      counseling smokers among first-year residents.

PMID- 11572540
TI  - Competing demands in the office visit: what influences mammography
      recommendations?
AB  - BACKGROUND: The multiple competing demands of the busy office visit have been
      shown to interfere with delivery of preventive services. In this study we used
      physician recommendations for screening mammography to examine the relative
      importance of physician, patient, and visit characteristics in determining on
      which patient visits this preventive service will be provided. METHODS:
      Physicians in the Ambulatory Sentinel Practice Network (ASPN) completed a
      questionnaire describing their knowledge, attitudes, and beliefs about screening
      mammography. They also described the content of a series of nonacute care visits
      with women aged 40 to 75 years with regard to making a recommendation when the
      patient was due for screening mammography. The data were linked, and univariate
      and multivariate logistic regression methods were used to examine the relative
      importance of physician, patient, and visit characteristics on making a
      recommendation for mammography. RESULTS: Ninety-three physicians reported making
      a recommendation for screening mammography on 53.1% of nonacute visits. When
      modeling physician, patient, and visit characteristics separately, 70% of the
      variability in the model is explained by physician characteristics only, 63% by
      patient characteristics only, and 73% by visit characteristics only. A combined
      model using all characteristics explained 85% of the variability. CONCLUSIONS:
      Although characteristics of physicians and patients can predict frequency of
      recommendations for mammography, the specific characteristics of the visit are
      equally important. Efforts to improve delivery of preventive services in primary
      care that emphasize physician education and performance feedback are unlikely to
      increase rates of mammography recommendation. Effective strategies must consider
      the multiple competing demands faced by patients and physicians during each
      office visit and seek ways for assisting them in setting rational priorities for
      services.

PMID- 11572541
TI  - From idea to market: the drug approval process.
AB  - BACKGROUND: Each year many new prescription drugs are approved by the Food and
      Drug Administration (FDA). The process of developing and bringing new drugs to
      market is important for primary care physicians to understand. METHODS: We
      describe the drug development process based on a review of the literature and Web
      sites addressing FDA processes and policies. RESULTS: The process starts with
      preclinical testing. For drugs that appear safe, an investigational new drug
      application is filed with the FDA. If approved, clinical trials begin with phase
      1 studies that focus on safety and pharmacology. Phase 2 studies examine the
      effectiveness of the compound. Phase 3 is the final step before submitting a new
      drug application (NDA) to the FDA. An NDA contains all the information obtained
      during all phases of testing. Phase 4 studies, or postmarketing studies, are
      conducted after a product is approved. Recent changes in legislation have
      streamlined the approval process. Critics contend that these changes have
      compromised public safety, resulting in the need to recall several products from
      the market. Proponents claim that changes in the approval process help patients
      with debilitating diseases, such as acquired immunodeficiency syndrome, that were
      previously denied critical medication because of bureaucratic regulations.

PMID- 11572542
TI  - Restless legs syndrome.
AB  - BACKGROUND: Restless legs syndrome is a common but not well-recognized central
      nervous system disorder that leads to insomnia and daytime distress. METHODS: A
      MEDLINE search of the recent English language literature was undertaken with
      review of appropriate articles and references. RESULTS: A growing body of work
      has added to an understanding of the epidemiology, diagnostic criteria,
      appropriate evaluation, and effective management of restless legs syndrome.
      CONCLUSIONS: Restless legs syndrome occurs in about 6% of the adult population,
      more so in the elderly. Affected patients experience uncomfortable sensations in
      the legs with inactivity, more pronounced late in the day and at bedtime, which
      are temporarily relieved by moving the limbs. Affected patients can suffer from
      insomnia, disrupted sleep, daytime fatigue, and difficulty with sedentary
      activities. Most cases are idiopathic, although secondary causes, such as iron
      deficiency, should be excluded. Dopaminergic agents are highly effective in
      treating restless legs syndrome, but side effects can be problematic. Alternative
      medications include benzodiazepines, opioids, gabapentin, and clonidine.

PMID- 11572544
TI  - Tarsal navicular stress fracture in a young athlete: case report with clinical,
      radiologic, and pathophysiologic correlations.
AB  - BACKGROUND: Tarsal navicular fractures are uncommon but important causes of foot
      pain. Being alert to this condition can help prevent a delay in the diagnosis.
      METHODS: A literature search of MEDLINE was undertaken, and a case report of an
      adolescent with tarsal navicular stress fracture is described. RESULTS AND
      CONCLUSIONS: Tarsal navicular fractures are often misdiagnosed for months.
      Because plain radiographs are unreliable, the diagnosis of tarsal navicular
      fractures requires the use of bone scan, fine-cut computed tomographic scans, or
      magnetic resonance imaging. Treatment requires strict non-weight-bearing
      activities to avoid complications. When the alert primary care physician can
      diagnose this condition, treatment of tarsal navicular fractures can be effective
      and rewarding.

PMID- 11572543
TI  - Group A streptococcal sepsis and ovarian vein thrombosis after an uncomplicated
      vaginal delivery.
AB  - BACKGROUND: Group A streptococcal puerperal sepsis is an uncommon peripartum
      infection that can quickly progress to a fulminant, multisystemic infection and
      life-threatening toxin-mediated shock. This infection can be asymptomatic during
      a short hospital stay after a routine delivery. Early treatment with antibiotics
      might not alter the course of tissue destruction caused by the exotoxin A.
      METHODS: Literature searches were performed using the key words "puerperal
      infections," "streptococcal infections," "septic sacroiliitis," "postpartum
      septic arthritis," and "postpartum ovarian vein thrombosis." After patient
      consent was obtained, a report was prepared documenting the disease course,
      diagnosis, and treatment of a case of puerperal sepsis with multiple serious
      complications. RESULTS AND CONCLUSION: Puerperal sepsis occurs when streptococci
      colonizing the genital tract or acquired nosocomially invade the endometrium,
      adjacent structures, lymphatics, and bloodstream. A lack of symptoms early in the
      course of infection is common; later, minor somatic complaints can quickly
      progress to septic shock as effects of the exotoxin A are manifest. Women who
      complain of fever, pelvic pain, or unexplained systemic symptoms in the early
      postpartum period should have a detailed history and physical examination. All
      sites of suspected infection should be cultured. If sepsis is suspected,
      diagnostic imaging includes chest radiographs, contrast-enhanced computed
      tomographic scans, or magnetic resonance imaging to rule out ovarian vein
      thrombosis, pelvic abscess, or sacroiliac septic arthritis. Broad-spectrum
      antibiotic coverage must be initiated immediately after collection of cultures.
      Clindamycin plus a beta-lactam antibiotic is preferred for streptococcal toxic
      shock syndrome.

PMID- 11572545
TI  - Horner syndrome from the dentist's chair.

PMID- 11572546
TI  - Sheehan syndrome: a rare complication of postpartum hemorrhage.

PMID- 11572547
TI  - Ramsay Hunt syndrome in a patient with human immunodeficiency virus infection.

PMID- 11572548
TI  - Using two alcohol screening tests with elderly patients.

PMID- 11572549
TI  - Evidence-based advertising?

PMID- 11572550
TI  - 24-hour ambulatory blood pressure monitoring.

PMID- 11572551
TI  - CPT coding by family physicians.

PMID- 11572552
TI  - Fragrances and allergic reactions.

PMID- 11572553
TI  - Sexually transmitted disease.

PMID- 11572554
TI  - Children of divorce.

PMID- 11572555
TI  - Refinement of an orthotopic lung cancer model in the nude rat.
AB  - Over 85% of people with lung cancer eventually succumb to this disease, largely
      because current chemotherapies are ineffective. The testing and validation of
      promising new approaches generally rely on achieving responses with cell lines in
      vitro or in tumor xenografts in nude mice. However, quite often the results seen
      with these models are not recapitulated in the clinic, thus necessitating the
      need for better animal models of lung cancer for preclinical testing of new
      therapies. One promising model is that of orthotopic lung cancer, where
      xenografts of human lung cancer are established in lungs of immunodeficient
      rodents. The problems associated with this model include poor rates of
      engraftment, limited tumor multiplicity, and a heightened risk for surgical
      trauma. The purpose of our study was to develop an efficient approach to
      engraftment of orthotopic tumors throughout the lungs of the Rowett nude rat.
      Initially, we augmented immunosuppression in the rats with whole-body X
      irradiation and then used orotracheal cannulas to intratracheally instill human
      cancer cells from the Calu-6 cell line. This protocol produced a low rate of
      engraftment and low tumor multiplicity. The hypothesis that slight disruption of
      the pulmonary epithelium or the surfactant layer would allow better tumor
      engraftment was tested by coadministration of either pancreatic elastase or
      ethylenediaminetetraacetic acid (EDTA) along with the cell instillations. Lung
      tumor engraftment was evaluated 8 weeks after instillation. The inclusion of
      elastase or EDTA with the Calu-6 cells resulted in an 80-100% engraftment rate,
      respectively. Coadministration of EDTA resulted in significantly larger and
      greater numbers of tumors/lung than those in elastase-treated animals. Temporal
      studies demonstrated that small nodules were scattered throughout the lung
      parenchyma 5 weeks after instilling Calu-6 cells and EDTA. These nodules grew to
      coalesce and form large masses that effaced >75% of the parenchyma at 9 weeks
      postinstillation. The refinements made through our studies have led to the
      development of an orthotopic lung cancer model that should facilitate the
      evaluation of novel therapies designed to treat or impede lung cancer
      development.

PMID- 11572556
TI  - Marek's disease virus infection in the brain: virus replication, cellular
      infiltration, and major histocompatibility complex antigen expression.
AB  - Marek's disease virus (MDV) infection in the brain was studied chronologically
      after inoculating 3-week-old chickens of two genetic lines with two strains of
      serotype I MDV representing two pathotypes (v and vv+). Viral replication in the
      brain was strongly associated with the development of lesions. Three viral
      antigens (pp38, gB, and meq) were detected in the brain of infected chickens.
      Marked differences between v and vv+ pathotypes of MDV were identified for level
      of virus replication, time course of brain lesions, and expression of major
      histocompatibility complex (MHC) antigens. Two pathologic phenomena (inflammatory
      and proliferative) were detected in the brain of chickens inoculated with vv+MDV,
      but only inflammatory lesions were observed in those inoculated with vMDV.
      Inflammatory lesions, mainly composed of macrophages, CD4+ T cells, and CD8+ T
      cells, started at 6-10 days postinoculation (dpi) and were transient.
      Proliferative lesions, characterized by severe infiltrates of CD4+CD8- T cells
      (blasts), started at 19-26 dpi and persisted. Expression of MHC antigens in
      endothelial cells and infiltrating cells within the brain was influenced by MDV
      infection. Upregulation of MHC class II antigen occurred in all treatment groups,
      although it was more severe in those inoculated with vv+MDV. MHC class I antigen
      was downregulated only in those groups inoculated with vv+MDV. These results
      enhance our understanding of the nature and pattern of MDV infection in the brain
      and help to explain the neurovirulence associated with highly virulent MDV.

PMID- 11572557
TI  - Feline Hodgkin's-like lymphoma: 20 cases (1992-1999).
AB  - We identified 20 cases of feline lymphadenopathy that conform to many clinical
      and histologic manifestations of human Hodgkin's disease. Histologic subtypes
      encountered included lymphocyte predominance (nine cases), mixed cellularity
      (nine cases), and nodular sclerosis (two cases). Two cases were not easily
      classified; fibrous bands were present, but the absence of nodules supported a
      subclassification of mixed cellularity Hodgkin's disease. Immunohistochemical
      staining of the tissues using antibodies against the pan T-cell antigen CD3, the
      human B-lymphocyte antigen 36 (BLA.36), the pan B-lymphocyte and plasma cell
      marker CD79a, and a myeloid antigen (MAC387) confirmed the phenotypic
      heterogeneity of the tumor. Classic Reed-Sternberg (RS) cells and mononuclear,
      multinucleate, and lacunar cell variants did not stain with any of the antibodies
      used. In contrast, lymphohistiocytic RS variants (L+H cells) reacted positively
      to BLA.36 and CD79a B-cell markers. Eighteen of 20 affected cats were > or = 6
      years of age (range, 1-14 years). A sex predilection could not be identified.
      These findings support the existence of Hodgkin's-like lymphoma in the cat.
      Proper identification of this disease in the cat will enable further
      characterization of clinical features and biologic behavior to determine whether
      there are significant differences in the treatment and prognosis of feline
      Hodgkin's-like lymphoma compared with non-Hodgkin's lymphoma.

PMID- 11572558
TI  - Evaluation of proliferative disorders in canine bone marrow by use of flow
      cytometric scatter plots and monoclonal antibodies.
AB  - The combination of flow cytometric scatterplot analysis and specific monoclonal
      antibodies was used to evaluate the lineage of cells from six dogs with
      proliferative disorders of bone marrow. Scatterplot analysis was used to identify
      mature and immature myeloid and erythroid cells. The immunophenotype of cells in
      the immature myeloid gate was determined by labeling cells with four monoclonal
      antibodies. These results were compared to results of cytologic and cytochemical
      evaluation. The immunophenotype of a dog with a diagnosis of myelogenous leukemia
      was a cluster of differentiation-18 (CD-18) positive, CD-14 negative, Thy-1
      negative, and a major histocompatibility complex (MHC) class II negative. The
      immunophenotype of a dog with a diagnosis of myelomonocytic leukemia was CD-18
      positive, CD-14 positive, Thy-1 positive, and MHC class II positive. Although
      this phenotype clearly differentiated myelomonocytic leukemia from myelogenous
      leukemia, it was similar to the immunophenotype of dogs with a diagnosis of
      malignant histiocytosis or hemophagocytic syndrome. The immunophenotype of two
      dogs with myelodysplastic syndrome was CD-18 positive and CD-14 negative. Results
      for Thy-1 and MHC class II were variable. As additional lineage-specific
      monoclonal antibodies become available, immunophenotyping should become a
      valuable tool for determination of the lineage of cells in canine
      myeloproliferative disorders.

PMID- 11572559
TI  - Heterophil function and resistance to staphylococcal challenge in broiler
      chickens naturally infected with avian leukosis virus subgroup J.
AB  - Avian leukosis virus subgroup J has a high tropism for myeloid lineage cells and
      frequently induces neoplastic transformation of myelocytes. The impact of
      congenital avian leukosis virus subgroup J infection on the function of
      circulating heterophils and susceptibility to staphylococcal infection was
      investigated. Six-week-old broiler chickens negative for exogenous avian leukosis
      viruses or congenitally infected with avian leukosis virus subgroup J were
      inoculated intravenously with 10(6) colony-forming units of Staphylococcus
      aureus, and pre- and postinoculation heterophil function was assessed. All
      chickens developed a leukocytosis with heterophilia after inoculation, but total
      leukocyte and heterophil counts were significantly higher in leukosis-negative
      chickens than in virus-infected chickens. Tenosynovitis was more severe in
      leukosis-negative chickens, and 2/10 (20%) of the virus-infected chickens had no
      histologic evidence of tenosynovitis. Osteomyelitis in the tibiotarsus or
      tarsometatarsus developed in 5/10 (50%) of the chickens in each group. S. aureus
      was recovered from the hock joint of 6/10 (60%) of the chickens in each group.
      Heterophils from all chickens exhibited similar phagocytic ability pre- and
      postinoculation. Heterophils from virus-infected chickens exhibited less
      bactericidal ability preinoculation than did heterophils from leukosis-negative
      chickens. However, postinoculation bactericidal ability was similar in both
      groups. Avian leukosis virus subgroup J provirus was present in heterophils
      isolated from congenitally infected chickens. Heterophils isolated from broiler
      chickens congenitally infected with avian leukosis virus subgroup J exhibit no
      significant functional deficits, and infected and uninfected chickens exhibit
      similar susceptibility to staphylococcal infection.

PMID- 11572560
TI  - Experimental reproduction of severe disease in CD/CD pigs concurrently infected
      with type 2 porcine circovirus and porcine reproductive and respiratory syndrome
      virus.
AB  - Three-week-old cesarean-derived colostrum-deprived (CD/CD) pigs were inoculated
      with porcine circovirus type 2 (PCV2, n = 19), porcine reproductive and
      respiratory syndrome virus (PRRSV, n = 13), concurrent PCV2 and PRRSV
      (PCV2/PRRSV, n = 17), or a sham inoculum (n = 12) to compare the independent and
      combined effects of these agents. Necropsies were performed at 7, 10, 14, 21, 35,
      and 49 days postinoculation (dpi) or when pigs became moribund. By 10 dpi,
      PCV2/PRRSV-inoculated pigs had severe dyspnea, lethargy, and occasional icterus;
      after 10 dpi, mortality in this group was 10/11 (91%), and all PCV2/ PRRSV
      inoculated pigs were dead by 20 dpi. PCV2-inoculated pigs developed lethargy and
      sporadic icterus, and 8/19 (42%) developed exudative epidermitis; mortality was
      5/19 (26%). PRRSV-inoculated pigs developed dyspnea and mild lethargy that
      resolved by 28 dpi. Microscopic lesions consistent with postweaning multisystemic
      wasting syndrome (PMWS) were present in both PCV2- and PCV2/PRRSV-inoculated pigs
      and included lymphoid depletion, necrotizing hepatitis, mild necrotizing
      bronchiolitis, and infiltrates of macrophages that occasionally contained
      basophilic intracytoplasmic inclusion bodies in lymphoid and other tissues. PCV2/
      PRRSV-inoculated pigs also had severe proliferative interstitial pneumonia and
      more consistent hepatic lesions. The most severe lesions contained the greatest
      number of PCV2 antigen-containing cells. PRRSV-inoculated pigs had moderate
      proliferative interstitial pneumonia but did not develop bronchiolar or hepatic
      lesions or lymphoid depletion. All groups remained seronegative to porcine
      parvovirus. The results indicate that 1) PCV2 coinfection increases the severity
      of PRRSV-induced interstitial pneumonia in CD/CD pigs and 2) PCV2 but not PRRSV
      induces the lymphoid depletion, granulomatous inflammation, and necrotizing
      hepatitis characteristic of PMWS.

PMID- 11572561
TI  - Localization of the initial developmental stages of Loma salmonae in rainbow
      trout (Oncorhynchus mykiss).
AB  - The intracellular microsporidian parasite Loma salmonae affects salmonids of the
      genus Oncorhynchus and is a significant cause of economic losses in pen-reared
      Chinook salmon (O. tshawytscha) in British Columbia. Loma salmonae infection is
      easily recognized by the xenomas that form in the gills, but early stages of
      infection are difficult to detect in histologic sections. In situ hybridization
      (ISH), using an L. salmonae-specific digoxigenin-labeled single-stranded DNA
      probe, was used to detect the parasite during the early stages of infection. Loma
      salmonae was detected in the gut mucosal epithelium as early as 24 hours
      postexposure (PE), and it localized in the lamina propria of the intestine within
      24 hours of infection. After the parasite was detected in the lamina propria,
      dividing merogonic stages in infected cells in the heart were detected by ISH as
      early as 2 days PE, providing the first evidence of parasitaemia and hematogenous
      distribution of this parasite in infected blood cells. The parasites inside the
      infected cells appeared to be undergoing merogony as they passed through the
      heart, indicating that proliferation may start at the site of infection, before
      the parasite arrives to the gills for their final developmental phase. This is
      the first time that L. salmonae passage through the intestinal wall and migration
      to the heart has been visualized; however, the identity of the cells harboring
      the parasite has yet to be determined.

PMID- 11572562
TI  - Haemophilus somnus isolated from a urachal abscess in a calf.
AB  - A urachal abscess was diagnosed in a 2-month-old, crossbred heifer that was
      presented for a distended abdomen and clinical signs of choking. Cultures of the
      mucopurulent exudate, obtained from within the mass on necropsy, yielded
      Haemophilus somnus. This is the first known documented report of H. somnus
      isolated from a urachal abscess.

PMID- 11572563
TI  - Fusobacteriosis in captive wild-caught pronghorns (Antilocapra americana).
AB  - An outbreak of Fusobacterium necrophorum-induced septicemia occurred in a group
      of 40 captive wild-caught pronghorns (Antilocapra americana). Primary
      pododermatitis or necrotic stomatitis progressed to produce fatal septicemia with
      metastatic lesions in the forestomachs, lung, liver, and cecum in 38 of the
      animals. Two remaining animals were euthanatized because of chronic
      pododermatitis. Housing the animals in a pasture previously used by bovids and
      heavy rains with persistence of ground water pools in the pasture were
      contributing factors in the pathogenesis of this outbreak.

PMID- 11572564
TI  - Clinicopathologic and electron microscopic study of cutaneous neuroendocrine
      (Merkel cell) carcinoma in a cat with comparisons to human and canine tumors.
AB  - Malignant neuroendocrine carcinoma of the skin (Merkel cell tumor) was diagnosed
      in an 18-year-old spayed female Maine Coon Cat. The diagnosis was made on the
      basis of morphologic and electron microscopic findings. The cat was euthanatized
      321 days after surgical excision of the tumor. The tumor's malignancy contrasted
      with the benign nature of Merkel cell tumors reported in dogs and was consistent
      with the malignancy of Merkel cell tumors reported in humans.

PMID- 11572565
TI  - Spontaneous neoplasms in captive African cane rats (Thryonomys swinderianus
      Temminck, 1827).
AB  - Despite the increasing importance of cane rat (Thryonomys swinderianus) farming
      in Africa, diseases of these animals in captivity are not well known. A survey of
      a colony in Gabon averaging 235 cane rats over a period of 36 months allowed the
      observation of several suspected tumors and the confirmation of three cases of
      neoplasms. Within a period of 8 months, a chondroma in an adult female, a
      hemangiosarcoma in a subadult male, and a chondrosarcoma in an elderly female
      were diagnosed. This incidence (1.3%) of neoplasms in the cane rat colony in such
      a short period is uncommon. Neoplasms in rodents might be induced by such factors
      as a high inbreeding coefficient, an oncogenic virus, or chemical agent
      intoxication. Although the etiology remains undetermined, these cases are
      described to provide baseline data on the pathology of this species in captivity.

PMID- 11572566
TI  - Radiculomeningomyelitis due to Halicephalobus gingivalis in a horse.
AB  - An adult horse was euthanatized following a clinical diagnosis of cauda equina
      neuritis. Significant gross postmortem and histopathologic findings were limited
      to the sacral spinal cord and cauda equina. The sacral spinal cord, meninges, and
      spinal nerve roots were expanded and partially effaced by sclerosing
      granulomatous inflammation with necrosis. The lesion contained numerous nematode
      larvae and fewer adults with a rhabditiform esophagus having a corpus, isthmus,
      and valved bulb. Female nematodes were amphidelphic and didelphic with reflexed
      ovaries. These morphologic features confirm Halicephalobus gingivalis as a novel
      cause of clinical signs in this case of cauda equina neuritis.

PMID- 11572567
TI  - Retroviral particles in neoplasms of Burmese pythons (Python molurus bivittatus).
AB  - Neoplastic diseases associated with retroviruses were diagnosed in four Burmese
      pythons (Python molurus bivattatus) from a single collection. Snake No. 1 was a 7
      year-old female with recurrent undifferentiated mesenchymal round cell tumor
      (lymphosarcoma) of the oral cavity. At necropsy, similar neoplastic masses were
      evident in the uterus and ovary, and there was diffuse involvement of the spleen.
      Snake No. 2 was a 4.5-year-old female that was euthanatized because of
      complications following resection of a segmental colonic adenocarcinoma. Snake
      No. 3 was a 5-year-old female that was euthanatized because of a large
      transitional cell carcinoma of the right kidney. Snake No. 4 was a 19-year-old
      female that was euthanatized following recurrence of an intermandibular
      fibrosarcoma. Ultrastructural examination revealed few to numerous extracellular
      and intracellular (intravacuolar) type C-like retroviral particles in all tumors.
      Tumors were about 90-95 nm in diameter, with an electron-dense core and bilaminar
      external membrane. The relationship of the intraneoplastic viral particles to the
      etiology of the tumors is uncertain.

PMID- 11572568
TI  - Reducing colorectal cancer through faecal occult blood screening: review of the
      evidence.

PMID- 11572569
TI  - Regulation of human hepatitis C virus replication by default RNA synthesis
      through transcription attenuation--a hypothesis.

PMID- 11572570
TI  - Characterization of the inflammatory infiltrate in peptic oesophagitis.
AB  - BACKGROUND: The diagnosis of oesophagitis is mainly based on histology, but
      interpretation of endoscopic biopsies is often difficult. We performed
      immunohistochemical studies on oesophageal biopsies to see if better
      characterization of the inflammatory cell infiltrate would improve the accuracy
      of the histologic diagnosis of gastro-oesophageal reflux disease. METHODS: The
      study groups consisted of 40 consecutive children (mean age +/- SD: 79.6 +/- 5l.9
      months; 20 boys) with gastro-oesophageal reflux disease and 7 symptomatic
      children (mean age +/- SD: 52.6 +/- 37.0 months; 3 boys) without gastro
      oesophageal reflux disease. All patients underwent upper gastrointestinal
      endoscopy with oesophageal biopsies. The diagnosis of gastro-oesophageal reflux
      disease was established by conventional endoscopic and histologic criteria. In
      each mucosal biopsy specimen, the number of intraepithelial CD3+, CD25+ (IL2
      receptor+), ICAM+, HLA-DR+ and mucosal mast cells were determined. RESULTS:
      Conventional histology was in close agreement with endoscopic findings (p<0.001)
      and reflected the clinical score even more than endoscopic findings. Conventional
      histology significantly correlated with each inflammatory immunohistochemical
      marker (<0.05 for each), but the markers were not predictive of symptom severity.
      Immunohistochemical markers were always abnormal in the gastro-oesophageal reflux
      disease patients, even in the mildest cases of oesophagitis. CONCLUSIONS:
      Although there is a good correlation between symptoms and histology, in a subset
      of patients, immunohistochemical studies appear useful in supporting the
      histological diagnosis of gastro-oesophageal reflux disease.

PMID- 11572571
TI  - Prevalence of gastric metaplasia in the duodenal bulb is low in Helicobacter
      pylori positive non-ulcer dyspepsia patients.
AB  - BACKGROUND: Gastric metaplasia in duodenum is a common phenomena in duodenal
      ulcer patients. However, the role of gastric metaplasia in patients with non
      ulcer dyspepsia is not clear. It is not known either whether Helicobacter pylori
      infected non-ulcer patients who are CagA-seropositive have gastric metaplasia in
      duodenum more often than CagA-negative patients. AIMS: To compare prevalence of
      gastric metaplasia in duodenum in non-ulcer dyspepsia patients according to
      Helicobacter pylori status. PATIENTS AND METHODS: A series of 400 unselected
      dyspeptic patients in primary care were investigated. Patients with no endoscopic
      evidence of organic disease (n=236) were enrolled in the study. Duodenal bulb and
      gastric biopsies were collected, as well as blood samples for Helicobacter pylori
      determination. RESULTS: There were no differences between CagA-seropositive and 
      seronegative Helicobacter pylori infected patients as far as concerns gastric
      metaplasia in duodenal bulb (20% vs 25%). Helicobacter pylori negative non-ulcer
      patients more often had gastric metaplastic changes (46%, p<0.0001) in duodenum.
      CONCLUSION: Helicobacter pylori infection has no major role in development of
      gastric metaplasia in duodenal bulb in non-ulcer dyspeptic patients. Furthermore,
      it does not result in positive CagA-serology, an increased risk for gastric
      metaplasia compared with CagA-seronegative cases.

PMID- 11572572
TI  - Role of autonomic dysfunction in patients with functional dyspepsia.
AB  - BACKGROUND: The role of autonomic dysfunction in patients with functional
      dyspepsia is not completely understood. AIMS: 1. to prospectively assess
      abnormalities of autonomic function in patients with functional dyspepsia, 2. to
      assess whether autonomic dysfunction in these patients is associated with a.
      visceral hypersensitivity or b. delayed gastric emptying or c. severity of
      dyspeptic symptoms. PATIENTS: A series of 28 patients with functional dyspepsia
      and 14 healthy volunteers without gastrointestinal symptoms were studied.
      METHODS: All patients and controls were submitted to a battery of five standard
      cardiovascular autonomic reflex tests, dyspeptic questionnaire, gastric barostat
      tests and gastric emptying tests. RESULTS: 1. Autonomic function tests showed
      that both sympathetic and parasympathetic scores of dyspeptic patients were
      significantly higher than in controls; 2. visceral hypersensitivity was confirmed
      in dyspeptics in response to proximal gastric distension, demonstrating lower
      pain threshold; 3. delayed gastric emptying occurred more frequently in patients
      with functional dyspepsia than in controls; 4. epigastric pain and epigastric
      burning were significantly more prevalent in patients with definite evidence of
      autonomic dysfunction; 5. No significant association was found between presence
      of autonomic dysfunction and presence of visceral hypersensitivity or presence of
      delayed gastric emptying in patients with functional dyspepsia. CONCLUSIONS: We
      concluded that a possible role of autonomic dysfunction in eliciting dyspeptic
      symptoms could not be determined from alterations in visceral hypersensitivity or
      delayed gastric emptying. Autonomic dysfunction might not be the major
      explanation for symptoms associated with functional dyspepsia.

PMID- 11572573
TI  - Measles is more prevalent in Crohn's disease patients. A multicentre Israeli
      study.
AB  - The question whether there is a transmissible pathogenetic agent as a cause for
      Crohn's disease, remains unanswered. Measles virus has been the subject of many
      intensive studies, in the attempt to find a role for it in the pathogenesis of
      inflammatory bowel disease. Whether an early infection with measles virus may
      predispose to Crohn's disease in later life is still not clear. We conducted a
      large scale multicentre study, in order to obtain sufficient data to answer this
      question. To do so, we compared inflammatory bowel disease patients, with Crohn's
      disease or ulcerative colitis, with two matched control groups: clinical
      controls, and community controls. A total of 531 patients, 271 with ulcerative
      colitis and 260 with Crohn's disease were interviewed, as well as 903 matched
      controls. Blood from 104 inflammatory bowel disease patients and 50 controls was
      tested for antibodies to measles virus. We did not find any differences related
      to measles vaccination, either in Crohn's disease or in ulcerative colitis.
      Exposure to measles in childhood was more frequent in Crohn's disease patients
      than in their controls, the difference being statistically significant (p < 0.05)
      in relation to community controls. The presence of IgG antibodies to measles
      virus was higher in patients with Crohn's disease than in patients with
      ulcerative colitis or controls (p = 0.084). Another observation of interest was
      the finding that Crohn's disease patients who had measles in childhood, more
      frequently had large bowel disease than those who had not had measles. These data
      lead us to postulate that there may be a role for measles infection in Crohn's
      disease, even if, at present, this role remains unclear.

PMID- 11572574
TI  - High prevalence, low pathogenicity of hepatitis G virus in kidney transplant
      recipients.
AB  - BACKGROUND: Prevalence and pathogenicity of hepatitis G virus infection in long
      term renal transplant recipients, are not fully known. AIM: To evaluate long-term
      impact of HGV infection on liver disease of renal transplanted patients. PATIENTS
      AND METHODS: A total of 155 hepatitis B surface antigen negative kidney
      transplant recipients, followed for a mean of 11 years after renal
      transplantation, were studied. Of these 48 (31%) patients had persistently
      elevated serum aminotransferase values. Frozen serum samples were tested for HGV
      RNA and HCV-RNA by nested reverse transcribed polymerase chain reaction, and for
      anti-hepatitis G virus and anti-hepatitis C virus by enzyme-linked immunosorbent
      assay Hepatitis C virus-RNA was typed by a line probe assay and quantified by a
      branched DNA signal amplification assay RESULTS: Hepatitis G virus-RNA was
      detected in 37 (24%) patients and anti-hepatitis G virus in another 26 (17%).
      Seventy (45%) patients had serum anti-hepatitis C virus and 63 of these (90%) had
      serum hepatitis C virus-RNA. Hepatitis G virus-RNA positive and negative patients
      were similar in terms of age, sex, duration of dialysis, rate of transfusion,
      chronic liver disease, rate of hepatitis C virus infection and immunosuppressive
      therapy. Fifteen (41%) hepatitis G virus-RNA seropositive patients were hepatitis
      C virus co-infected. Hepatitis C virus-RNA levels were significantly lower in the
      15 hepatitis C virus/hepatitis G virus co-infected patients than in the 48
      patients with hepatitis C virus infection only (2.2 vs 10.8 MEq/ml, p = 0.02).
      Only 3 hepatitis G virus carriers had persistently elevated alanine
      aminotransferase compared to 29 hepatitis C virus carriers (14% vs 60%, p <
      0.001), 10 patients co-infected with both hepatitis G virus and hepatitis C
      virus, and in 6 patients with neither infection (67% vs 8%, p < 0.001).
      CONCLUSIONS: Hepatitis G virus infection is common among kidney transplant
      patients, it carries a low risk of chronic liver disease even in long-term follow
      up. Low levels of hepatitis C virus-RNA found in hepatitis G virus carriers
      suggest an interaction between these two viruses in immunosuppressed patients.

PMID- 11572575
TI  - Are there any subgenomic forms of hepatitis C virus RNA in the liver?
AB  - BACKGROUND: Hepatitis C virus has a single stranded positive RNA genoma. Although
      believed to replicate via semi-conservative transcription of a negative-stranded,
      genomic-length RNA intermediate, detailed steps of its replicative cycle are
      unknown. AIMS: To quantify some of intrahepatic hepatitis C virus RNA forms, as
      inferred from comparison with replication of other members of the Flaviviridae
      family. PATIENTS AND METHODS: Genomic and negative-stranded hepatitis C virus RNA
      were semi-quantitated by strand-specific reverse transcriptase-polymerase chain
      reaction at both their 5' and 3' ends in liver of 10 patients with recurrent
      hepatitis C after liver transplantation. RESULTS: Our data are consistent with
      the existence of hitherto unrecognized, very large amounts (up to approximately
      10,000 fold the amount of the replication intermediate proper) of subgenomic
      hepatitis C virus RNAs of genomic polarity, starting in the 5' untranslated
      region, of unknown length. Similarly, subgenomic RNAs of negative polarity,
      starting in the 3' untranslated region, may also be produced, albeit to a less
      extent. We found no correlation between the amount of these forms and any
      clinical, histological or virological feature. However, the number of subgenomic
      RNA molecules of negative polarity tended to be inversely correlated with
      viraemia (r = 0.7, p = 0.058), suggesting their possible role in controlling rate
      of virion production. CONCLUSIONS: Hepatitis C virus replication results in
      transcription of huge amounts of subgenomic RNAs both of genomic and negative
      polarity, which may either regulate translation of excess structural antigens of
      hepatitis C virus, or play the role of defective RNAs interfering with viral
      replication. A revised model of hepatitis C virus RNA replication is proposed.

PMID- 11572576
TI  - Takayasu's arteritis and Crohn's disease: an unusual association. Report on two
      cases.
AB  - Two cases of Takayasu's arteritis associated with Crohn's disease of the colon
      are described, both of which occurring in young female patients. In the first
      case, the vasculitic process was widespread, involving the aortic arch, the
      abdominal aorta, the renal arteries and the left iliac artery, similar to the
      angiographic "Indian" pattern. The second case presented a typical "Japanese"
      aortic arch involvement. In the first patient, Crohn's disease appeared to have
      been present prior to Takayasu's arteritis, vice versa in the second case;
      steroid treatment, assigned for both diseases might, however, have modified their
      natural evolution. The association is rare. Moreover, the coexistence of two
      immune-mediated diseases in the same subject is unusual as they are generally
      considered to be independent. Hypotheses concerning their possible inter
      relationship are advanced.

PMID- 11572577
TI  - Vegetarian diets in hepatic encephalopathy: facts or fantasies?
AB  - Diet treatment characterized by a reduction in or a selection of food proteins is
      currently suggested in hepatic encephalopathy. This article is a review of the
      present knowledge about the characteristics and the rationale of vegetarian diets
      in cirrhotic patients with overt or latent encephalopathy. In addition, evidence
      relating diet and encephalopathy and the nutritional features and needs of
      cirrhotic patients is reported. Finally, the rationale of a diet based on
      vegetable and milk-derived proteins that may overcome the limits and the possible
      adverse effects of a strict vegetarian diet is presented.

PMID- 11572578
TI  - Metolazone-induced cholestatic liver disease.

PMID- 11572579
TI  - Gabexate mesilate in acute pancreatitis: neither a miracle nor a mirage, merely
      the search of optimal dosage.

PMID- 11572580
TI  - Personal experience in advanced pancreatic cancer: retrospective analysis on the
      use of 5-fluorouracil or gemcitabine.

PMID- 11572581
TI  - Elevated risk for colorectal neoplasms among first-degree relatives of patients
      with colorectal adenomatous polyps.

PMID- 11572582
TI  - Correlation of aerobic biodegradability of sulfonated azo dyes with the chemical
      structure.
AB  - The reported data of biodegradability of variously substituted 25 sulfonated azo
      dyes were divided into two classes: 8 dyes designated "rapidly biodegradable" and
      17 dyes "not rapidly biodegradable", by applying principal components analysis
      (PCA). The biodegradability of the dyes was modeled with the discriminant
      technique of two-value regression analysis based on structural descriptors. A
      statistically significant and biologically meaningful regression model that gives
      perfect classification was obtained, and the results were compared with the
      previous qualitative interpretation of the substituent effects on biodegradation.
      The coefficients of the regression model revealed a significant interaction
      between ring substituents for biodegradability. The results facilitate
      understanding of the mechanism of degradation.

PMID- 11572583
TI  - Degradation of ethylene glycol using Fenton's reagent and UV.
AB  - Oxidation of ethylene glycol in aqueous solutions was found to occur with the
      addition of Fenton's reagent with further conversion observed upon UV
      irradiation. The pH range studied was 2.5-9.0 with initial H2O2 concentrations
      ranging from 100 to 1000 mg/l. Application of this method to airport storm-water
      could potentially result in reduction of chemical oxygen demand by conversion of
      ethylene glycol to oxalic and formic acids. Although the amount of H2O2 added
      follows the amount of ethylene glycol degraded, smaller H2O2 doses were
      associated with increases in the ratio of ethylene glycol removed per unit H2O2
      added indicating the potential of pulsed doses or constant H2O2 feed systems.
      Ethylene glycol removal was enhanced by exposure to UV light after treatment with
      Fenton's reagent, with rates dependent on initial H2O2 concentration. In addition
      to ethylene glycol, the principle products of this reaction, oxalic and formic
      acids, have been shown to be mineralized in other HO generating systems
      presenting the potential for ethylene glycol mineralization in this system with
      increased HO* production.

PMID- 11572584
TI  - The fate of linear alcohol ethoxylates during activated sludge sewage treatment.
AB  - Model continuous activated sludge (CAS) plants (Husmann units) were used to study
      the fate of two commercial, alcohol ethoxylate (AE) surfactants during aerobic
      sewage treatment. The surfactants were produced by the ethoxylation of an
      essentially linear C(12-15) alcohol (NEODOL 25) with an average of 7 (C(12
      15)EO7) or 3 (C(12-15)EO3) moles of ethylene oxide (EO). Recent analytical
      developments made it possible to measure levels of AE that included the free
      alcohol and EO1 oligomers across the CAS system, from the influent feed, on the
      activated sludge, through to the effluent. Measured concentrations of AE (as C(12
      15)EO(0-20)) in the synthetic sewage feeds to the test CAS plants lay in the
      range 11-13 mg/l. During stable operation at 20 degrees C, an average of 5
      microg/l AE were present in the C(12-15)EO7 CAS plant effluent, giving a removal
      (bioelimination) of >99.9%. When levels of AE on the sludge, and polyethylene
      glycols (PEGs--an expected biodegradation intermediate) in the effluent and on
      the sludge were also taken into account, biodegradation was considered to be
      responsible for >98.7% of the observed removal. During operation at a winter
      temperature (10 degrees C), an average of 26 microg/l AE were present in the C(12
      15)EO7 CAS plant effluent, giving a removal of 99.8%. Biodegradation was
      estimated to be responsible for >97.2% of the observed removal. During operation
      at 20 degrees C, an average of 7 microg/l AE were present in the C(12-15)EO3 CAS
      plant effluent, giving a removal of >99.9%. No analysis for PEG was performed in
      this case but the low level of AE on the sludge (0.2 mg/g dry solids) suggested
      that biodegradation was responsible for most of the observed removal. Neither
      surfactant had any adverse effect on the sewage treatment efficiencies of the CAS
      plants in terms of dissolved organic carbon (DOC) removal, nitrification or
      biomass levels.

PMID- 11572585
TI  - Enhanced degradation of polycyclic aromatic hydrocarbons by biodegradation
      combined with a modified Fenton reaction.
AB  - A study has been conducted to enhance degradation of a mixture of polycyclic
      aromatic hydrocarbons (PAHs) by combining biodegradation with hydrogen peroxide
      oxidation in a former manufactured gas plant (MGP) soil. An active bacterial
      consortium enriched from the MGP surface soil (0-2 m) biodegraded more than 90%
      of PAHs including 2-, 3-, and 4-ring hydrocarbons in a model soil. The consortium
      was also able to transform about 50% of 4- and 5-ring hydrocarbons in the MGP
      soil. As a chemical oxidant, Fenton's reagent (H2O2 + Fe2+) was very efficient in
      the destruction of a mixture of PAHs (i.e., naphthalene (NAP), fluorene (FLU),
      phenanthrene (PHE), anthracene (ANT), pyrene (PYR), chrysene (CHR), and
      benzo(a)pyrene (BaP)) in the model soil; noticeably, 84.5% and 96.7% of initial
      PYR and BaP were degraded, respectively. In the MGP soil, the same treatment
      destroyed more than 80% of 2- and 3-ring hydrocarbons and 20-40% of 4- and 5-ring
      compounds. However, the low pH requirement (pH 2-3) for optimum Fenton reaction
      made the process incompatible with biological treatment and posed potential
      hazards to the soil ecosystem where the reagent was used. In order to overcome
      such limitation, a modified Fenton-type reaction was performed at near neutral pH
      by using ferric ions and chelating agents such as catechol and gallic acid. By
      the combined treatment of the modified Fenton reaction and biodegradation, more
      than 98% of 2- or 3-ring hydrocarbons and between 70% and 85% of 4- or 5-ring
      compounds were degraded in the MGP soil, while maintaining its pH about 6-6.5.

PMID- 11572586
TI  - Speciation and mobility of cadmium in straw and wood combustion fly ash.
AB  - Two fly ashes from biomass combustion have been analysed regarding cadmium
      speciation and mobility. A fly ash from straw combustion contained 10 mg Cd/kg
      dry matter, and around 50% of the cadmium was leachable in water. The possible
      main speciation of cadmium in this fly ash was CdCl2. When adding this fly ash to
      agricultural soil a threat for groundwater contamination and plant uptake is
      existing. A fly ash from wood chip combustion had 28.6 mg Cd/kg dry matter. In
      this fly ash, the cadmium was bound more heavily, with only small amounts of
      cadmium leached in mild extractants. A possible speciation of cadmium in this fly
      ash was as oxide or as CdSiO3. Long-term effects and accumulation of cadmium
      could be a problem when adding this fly ash to agricultural or forest soils.

PMID- 11572587
TI  - EDTA and HEDTA effects on Cd, Cr, and Ni uptake by Helianthus annuus.
AB  - Phytoremediation has shown great potential as an alternative treatment for the
      remediation of heavy-metal-contaminated soils and groundwater. However, the lack
      of a clear understanding pertaining to metal uptake/translocation mechanisms,
      enhancement amendments, and external effects on phytoremediation has hindered its
      full-scale application. The objective of this research was to investigate the
      ability of synthetic chelators for enhancing the phytoremediation of cadmium-,
      chromium- and nickel-contaminated soil. Ethylenediaminetriacetic acid (EDTA) and
      N-(2-hydroxyethyl)-ethylenediaminetriacetic acid (HEDTA) were applied to the soil
      at various dosages to elevate metal mobility. Uptake into and translocation
      within Helianthus annuus was determined. It was found that EDTA at a rate of 0.5
      g/kg significantly increased the shoot concentrations of Cd and Ni from 34 and 15
      to 115 and 117 mg/kg, respectively. The total removal efficiency for EDTA was 59
      microg/plant. HEDTA at the same application rate resulted in a total metal uptake
      of 42 microg/plant. These research demonstrated that chelator enhancement is
      plant- and metal-specific and is subjective to inhibition when multiple heavy
      metals are present. Results also showed that chelator toxicity reduced the
      plant's biomass, thereby decreasing the amount of metal accumulation.

PMID- 11572588
TI  - Intermediate inhibition in the heterogeneous UV-catalysis using a TiO2 suspension
      system.
AB  - Langmuir-Hinshelwood (L-H) kinetic expression was used to develop a basic
      mathematical model, which could describe the inhibition of intermediates in the
      photocatalysis of 2-chlorophenol (2-CP) in a suspended TiO2 system. Results
      showed that the photocatalytic oxidation of 2-chlorophenol followed the L-H type
      behavior and the reaction by-products displayed an inhibiting effect on the
      degradation rate. The inhibition was estimated by comparing to observed and
      estimated half-lives. The higher the initial concentration of 2-chlorophenol, the
      higher the inhibition of photocatalytic reaction. The L-H kinetic has been
      modified slightly in this study to rationalize the contrast of inhibited behavior
      and to improve in favor of a surface reaction. The concentrations of 2
      chlorophenol were investigated ranging from 7.78 x 10(-5) to 7.78 x 10(-4) mol l(
      1). The degradation of 2-chlorophenol in this reaction condition approximates a
      first-order kinetics to near-complete degradation. Calculated kinetic profiles
      are in an excellent agreement with the experimental observation. The results of
      the theoretical analysis can be used to estimate reaction rates in different
      initial concentrations of target compound.

PMID- 11572589
TI  - Electrochemical oxidation of bisphenol A. Application to the removal of bisphenol
      A using a carbon fiber electrode.
AB  - The electrochemical behavior of bisphenol A was investigated by voltammetric
      techniques. The electrochemical oxidation of bisphenol A led to the inactivation
      of the glassy carbon electrode as the result of the deposition of the
      electropolymerized films. Although phenolate is oxidized more easily than the
      neutral phenol, an electropolymerized film of bisphenol A was formed in neutral
      media rather than in alkaline media. The fouling of the electrode surface by the
      electropolymerized film was evaluated by monitoring the electrode response of
      ferrocyanide ion as the redox marker. The electrochemical removal of bisphenol A
      based on the formation of the electropolymerized film on an anode surface was
      also attempted using a carbon fiber electrode with a very large surface area. The
      high removal efficiency for bisphenol A was obtained in a dilute solution of
      bisphenol A. The maximum surface coverage (gamma) of electropolymerized bisphenol
      A on the carbon fiber was about 2 x 10(-9) mol/cm2.

PMID- 11572590
TI  - Aerobic dehalogenation potentials of four bacterial species isolated from soil
      and sewage sludge.
AB  - Four bacterial species each were isolated from soil and a sewage oxidation pond
      using enrichment culture technique, and the bacterial isolates were identified to
      belong to the two genera Bacillus and Corynebacterium. The axenic cultures of the
      isolates utilized monochloroacetic acid (MCA), trichloroacetic acid (TCA), CHCl3
      and CCl4 for growth up to 1 g substrate l(-1) (w/v) and growths were enhanced in
      the mixed cultures of the isolates. The specific growth rate constants in the
      media ranged from 0.144 to 0.475. This is lower than the comparatively high
      values observed for the glucose medium, which varied significantly (P < 0.05)
      between 0.699 and 0.792 h(-1). Serial adaptation of the individual isolates in
      the organochloride media significantly (P < 0.05) affected the bacteria growth
      yields. The dehalogenase specific activity observed in the cell-free extracts of
      the mixed cultures of the isolates was significantly higher (P < 0.05) than those
      of their respective monocultures. Optimal pH of the dehalogenase activity was
      between 7.6 and 8.0, while temperature optima were between 30 degrees C and 35
      degrees C.

PMID- 11572591
TI  - Adsorption of acid dye onto activated carbons prepared from agricultural waste
      bagasse by ZnCl2 activation.
AB  - A series of activated carbons were prepared from agricultural waste sugarcane
      bagasse by chemical activation with zinc chloride (ZnCl2) as an activating agent
      at 500 degrees C and 0.5 h soaking time. The Langmuir surface area and total pore
      volume were used to estimate the average pore diameter of the carbon products.
      The values of the surface area and pore volume increased linearly with increase
      in the impregnation ratio (IR) up to 100 wt%. The adsorption capacities of the
      derived adsorbents for Acid Orange 10 were measured at 20 degrees C and 40
      degrees C to gain further insights into the acidic surface oxides of the
      adsorbent from the results of Fourier transform infrared (FTIR) spectroscopy
      analysis and pH measurement. Adsorption isotherms of the acid dye on adsorbents
      prepared were determined and correlated with common isotherm equations. It was
      found that the Langmuir model appears to fit the isotherm data better than the
      Freundlich model. The physical properties of these adsorbents were consistent
      with the parameters obtained from the isotherm equations.

PMID- 11572592
TI  - Substituent effects on azo dye oxidation by the FeIII-EDTA-H2O2 system.
AB  - The effect of substituents on the oxidation of azo dyes in the FeIII-EDTA-H2O2
      system was examined at pH 7. 4-(4'-sulfophenylazo)phenol and 2-(4'
      sulfophenylazo)phenol, with methyl, methoxy, and halo substituents on the
      phenolic ring, were used as model systems. Oxidation of the naphthol dyes Orange
      I and Orange II were also examined. All of the dyes tested were decolorized in
      the FeIII-EDTA-H2O2 system, but the degree of decolorization varied over a factor
      of 10. Dyes substituted with one or two halogens were oxidized to a greater
      extent than the corresponding methyl- or methoxy-substituted dyes. One
      explanation for the effect of halogen substituents is that they make the phenolic
      moieties more acidic, which favors the phenolate anion, which is more readily
      attacked by *OH. This explanation is supported by the observed correlation
      between charge density of the phenolate anion and the degree of decolorization.
      Based on an analysis of products formed from Orange II, a probable mechanism for
      decolorization of phenolic azo dyes by *OH is proposed. In addition, the optimal
      levels of H2O2 needed for the process have been examined. It appears that high
      levels of H2O2 could reduce decolorization by scavenging the *OH.

PMID- 11572593
TI  - Effects of a non-ionic surfactant (Tween-80) on the mineralization, metabolism
      and uptake of phenanthrene in wheat-solution-lava microcosm.
AB  - Effects of a non-ionic surfactant (Tween-80) on the mineralization, metabolism
      and uptake of phenanthrene in wheat-solution-lava microcosm were studied using
      14C-labeled phenanthrene. The mineralization and metabolism of phenanthrene were
      fast in such a system. At least 90% of the applied phenanthrene were transformed
      within 24 days. Only 0.3% of the applied 14C-activity were identified to be the
      parent phenanthrene. Most of the applied 14C-activity (70%) was recovered from
      wheat, in which ca. 70% were associated with wheat shoots (stems and leaves) and
      ca. 30% wheat roots. 33% and 20% of the applied 14C-activity had been constructed
      into wheat tissues of shoots and roots, respectively. The 14C-activity recovered
      in forms of CO2 and volatile organic chemicals (VOCs) was 12-16% and 4-5%,
      respectively. The major metabolites of phenanthrene were polar compounds (18% of
      the applied 14C) and only 2.1% were identified as non-polar metabolites. No
      phenanthrene was found in wheat shoots indicating that it could not be
      transported from roots to upper parts of the plant but in form of metabolites
      (mostly polar metabolites). Foliar uptake of 14C-activity via air in form of
      14CO2 occurred. The presence of Tween-80 significantly enhanced the degradation
      of phenanthrene, which could be attributed to its increase of microbial
      activities in the system. Tween-80 also significantly (P < 0.05) reduced the
      phenanthrene level in wheat roots, which probably resulted from desorption of
      phenanthrene from root surface caused by the surfactant.

PMID- 11572594
TI  - Solar photocatalytic decolorization of methylene blue in water.
AB  - In this study, a photocatalytic decolorization system equipped with immobilized
      TiO2 and illuminated by solar light was used to remove the color of wastewater.
      To examine the decoloring efficiency of this system, photocatalytic
      decolorization of an organic dye such as methylene blue was studied as an
      example. The effects of light source, pH, as well as the initial concentration of
      dye were also investigated. It was observed that the solution of methylene blue
      could be almost completely decolorized by the solar light/TiO2 film process while
      there was about 50% color remaining with solar irradiation only. In addition, it
      was found that the decoloring efficiency of solution was higher with solar light
      irradiation than with artificial UV light irradiation, even though the artificial
      UV light source supplied higher UV intensity at 254 nm. The color removal rate of
      methylene blue with solar light irradiation was almost twice that of artificial
      UV light irradiation. This phenomena was mainly attributed to that some visible
      light range of solar light was useful for exciting the methylene blue molecules
      adsorbed on TiO2 film, leading to a photosensitization process undergoing and
      decoloring efficiency promoted. This solar-assisted photocatalytic device showed
      potential application for decoloring organic dyes in wastewater.

PMID- 11572595
TI  - Kinetic model for phenolic compound oxidation by Fenton's reagent.
AB  - A kinetic model is developed for the oxidation of phenolic compounds by Fenton's
      reagent. In the first stage a rigorous kinetic model is applied to calculate the
      different kinetic rate constants for the oxidation process of p-hydroxybenzoic
      acid. In a second phase a competitive method is applied to calculate these
      kinetic constants for another 10 phenolic compounds present in agroindustrial and
      pulp paper wastewaters. These 10 phenolic compounds were: beta-resorcylic acid, 3
      (4-hydroxyphenyl)-propionic acid, ferulic acid, protocatechuic acid, caffeic
      acid, p-coumaric acid, vanillic acid, syringic acid, veratric acid and 3,4,5
      trimethoxybenzoic acid.

PMID- 11572596
TI  - Comparisons of metal leachability for various wastes by extraction and leaching
      methods.
AB  - The objective of this research was to evaluate three extraction tests, i.e.,
      toxicity characteristic leaching procedures (TCLP), extraction procedure (EP),
      and American Society for Testing and Materials (ASTM) methods, for their ability
      to extract metals in chemical sludge and incineration bottom ash, in terms of the
      precision of analytical results. Typical chemical sludges, including the
      electroplating and dye-stuff sludges, the municipal solid waste incineration
      bottom ash, the leather debris, and the steel-mill bottom residue containing Cd,
      Cr, Cu, Pb, and Zn were prepared for the lysimetry test (dynamic testing) to
      compare with the extraction results. Results show that for bottom residue and dye
      stuff sludge, the concentration of metal leached was almost the same between the
      lysimetry leaching and the TCLP tests. The metal concentration followed the
      order: TCLP approximately = EP > ASTM. TCLP and EP exhibited almost the same
      relative standard deviation (RSD) value. Therefore, the results of the TCLP tests
      for bottom residue and dye-stuff sludge, which have a low metal content and
      alkalinity, can be used to estimate the metal concentration leached by typical
      acid rain in Taiwan; whereas the ASTM extraction test may be a better indicator
      of the lysimetry test.

PMID- 11572597
TI  - In vivo inhibition of cyclooxygenase-2 by a selective phosphorothioated
      oligonucleotide.
AB  - Inhibition of cyclooxygenase-2 (cox-2) is considered to be anti-inflammatory,
      whereas inhibition of the constitutive isozyme cox-1 causes renal and
      gastrointestinal toxicity. Therefore, to achieve an optimal anti-inflammatory
      effect, an inhibitor should be cox-2 selective without inhibiting cox-1. For this
      purpose, 10 different cox-2-selective phosphorothioated oligonucleotides (S
      oligos) were tested to inhibit the cox-2 enzyme selectively in vivo. An aqueous
      solution of these S-oligos (3 mg/kg body weight) was injected intraperitoneally
      (i.p.) into male Sprague-Dawley rats with colitis induced by trinitrobenzene
      sulfonic acid (TNBS). The colonic levels of cox-2 protein, mRNA, myeloperoxidase
      (MPO), and prostaglandin E2 (PGE2) were increased significantly on day 1 and
      remained significantly elevated until day 7 post-TNBS administration, whereas cox
      1 remained unaltered. Two S-oligos were found to be effective in reducing the
      level of cox-2 protein selectively without any effect on the cox-1. The effective
      S-oligo, but not the mismatched control oligo, reduced the tissue levels of PGE2
      and MPO activity significantly. The effective S-oligo reduced the level of cox-2
      but not the cox-1 mRNA significantly, whereas a mismatched or a sense control
      oligo did not affect the levels of these isoforms. M-fold analysis demonstrated
      extensive secondary structure formation in the cox-2 mRNA. These findings
      demonstrate that only a few selected sites in the cox-2 target mRNA are
      accessible in vivo, probably because of the presence of secondary structures.
      Suppression of cox-2 protein, PGE2, and MPO activity by the S-oligo might prove
      to be an anti-inflammatory property.

PMID- 11572598
TI  - Aromatic polyamidines inhibiting the Tat-induced HIV-1 transcription recognize
      structured TAR-RNA.
AB  - We have investigated the effects of aromatic polyamidines on HIV-1 transcription.
      We found a block to Tat-induced HIV-1 transcription assessed by inhibition of CAT
      activity in HL3T1 cells at a concentration lower than the IC50 value, suggesting
      that molecules with three (TAPB) and four (TAPP) benzamidine rings could be
      useful against HIV-1. In contrast, aromatic polyamidines with only two
      benzamidine rings (DAPP) did not block Tat-induced transcription. We reasoned
      that this effect could be due to binding of TAPB and TAPP to HIV-1 TAR RNA. By
      EMSA and filter binding assays, we studied possible interactions of aromatic
      polyamidines with HIV-1 TAR RNA. Wild-type TAR RNA or TAR RNA with mutations in
      the stem or bulge sequences, but retaining the stem-loop structure, was used to
      define the RNA-binding activities of these compounds. Our data suggest that
      aromatic polyamidines with two (DAPP) and four (TAPP) benzamidine rings,
      respectively, do not bind to TAR RNA or bind without sequence selectivity.
      Interestingly, an aromatic polyamidine with three benzamidine rings (TAPB)
      recognizes the wild-type TAR RNA in a specific manner. Furthermore, we found that
      introduction of one halogen atom into the benzamidine rings strongly increases
      the RNA-binding activity of these compounds.

PMID- 11572599
TI  - Specific inhibition of estrogen receptor alpha function by antisense
      oligodeoxyribonucleotides.
AB  - We have tested the effect of a range of antisense oligodeoxyribonucleotides (ODN)
      directed against the human estrogen receptor alpha (ERalpha) on ERalpha protein
      expression and function. Antisense ERalpha ODN transfected into the ERalpha
      positive human breast carcinoma cell line MCF7-K2 showed variable responses
      dependent on the oligo used. The most active antisense ODN (oligo 7) decreased
      the levels of ERa protein by 61% as measured by Western blot analysis. Exogenous
      17beta-estradiol (17beta-E2), but not 17alpha-E2, augmented this effect, with a
      threshold effect at 10(-8) M 17beta-E2. The inhibitory effect of antisense ERa
      oligo 7 was confirmed by measurement of functional ERalpha protein. 3H-17beta-E2
      binding to MCF7 cell extracts was inhibited to approximately 40% of control
      values in the presence of oligo 7. Antisense-transfected MCF7-K2 cell cultures
      produced a further 30% binding reduction in the presence of exogenous 17beta-E2.
      An inhibitory effect on 17beta-E2-dependent cell function was confirmed by the
      demonstration that ERalpha oligo 7-transfected MCF7-K2 cells failed to exhibit
      17beta-E2-stimulated cell proliferation. Exogenous 17beta-E2 enhanced the
      inhibitory effect of the antisense ODN by increasing ODN transfection efficiency
      but without ERalpha catabolism via the proteosomal pathway, suggesting an effect
      of 17beta-E2 on the plasma membrane and the existence of different ERalpha
      degradation pathways in the MCF7-K2 cell subclone. As 17beta-E2 had no effect on
      ERalpha protein degradation, we conclude that the observed reduction of ERalpha
      protein levels is due solely to the presence of the antisense ERalpha ODN.
      Antisense ERalpha ODN molecules, therefore, may form the basis of effective
      therapies against ERalpha-dependent malignancies.

PMID- 11572600
TI  - Competitive binding of triplex-forming oligonucleotides in the two alternate
      promoters of the PMP22 gene.
AB  - Overexpression of the 22-kDa peripheral myelin protein (PMP22) causes the
      inherited peripheral neuropathy, Charcot-Marie-Tooth disease type 1A (CMT1A). In
      an attempt to alter PMP22 gene expression as a possible therapeutic strategy for
      CMT1A, antiparallel triplex-forming oligonucleotides (TFO) were designed to bind
      to purine-rich target sequences in the two PMP22 gene promoters, P1 and P2.
      Target region I in P1 and region V in P2 were also shown to specifically bind
      proteins in mammalian nuclear extracts. Competition for binding of these targets
      by TFO vs. protein(s) was compared by exposing proteins to their target sequences
      after triplex formation (passive competition) or by allowing TFO and proteins to
      simultaneously compete for the same targets (active competition). In both
      formats, TFO were shown to competitively interfere with the binding of protein to
      region I. Oligonucleotides directed to region V competed for protein binding by a
      nontriplex-mediated mechanism, most likely via the formation of higher-order,
      manganese-destabilizable structures. Given that the activity of the P1 promoter
      is closely linked to peripheral nerve myelination, TFO identified here could
      serve as useful reagents in the investigation of promoter function, the role of
      PMP22 in myelination, and possibly as rationally designed drugs for the therapy
      of CMT1A. The nontriplex-mediated action of TFO directed at the P2 promoter may
      have wider implications for the use of such oligonucleotides in vivo.

PMID- 11572601
TI  - CpG stimulation of primary mouse B cells is blocked by inhibitory
      oligodeoxyribonucleotides at a site proximal to NF-kappaB activation.
AB  - Bacterial DNA and CpG-oligodeoxyribonucleotides (ODN) are powerful B cell
      activators, inducing apoptosis protection, cell cycle entry, proliferation,
      costimulatory molecule expression, immunoglobulin (Ig) and interleukin-6 (IL-6)
      secretion. However, proximal events in B cell activation by ODN are only
      partially characterized, including the translocation of NF-kappaB to the nucleus.
      In this paper, we provide evidence that CpG-ODN-induced cell cycle entry and
      apoptosis protection are blocked by SN50 or gliotoxin and thus require NF-kappaB
      activation. NF-kappaB activation occurred within 30 minutes of stimulation of
      murine B cells with a phosphorothioate (S) CpG-ODN and persisted for up to 40
      hours, with p50, p65, and c-Rel as the major components. Similar to other NF
      kappaB inducers, CpG-ODN caused an early IkappaBalpha and IkappaBbeta degradation
      plus cleavage of the p50 precursor and subsequent NF-kappaB nuclear
      translocation. A group of closely related S-ODN, which specifically blocked CpG
      induced B cell activation at submicromolar concentrations, also prevented NF
      kappaB DNA binding and transcriptional activation. These inhibitory S-ODN
      differed from stimulatory S-ODN by having 2-3 G substitutions in the central
      motif. As inhibitory S-ODN did not directly interfere with the NF-kappaB DNA
      binding but prevented CpG-induced NF-kappaB nuclear translocation of p50, p65,
      and c-Rel and blocked p105, IkappaBalpha, and IkappaBbeta degradation, we
      concluded that their putative target must lie upstream of inhibitory kinase (IKK)
      activation.

PMID- 11572602
TI  - Uptake dynamics and retinal tolerance of phosphorothioate oligonucleotide and its
      direct delivery into the site of choroidal neovascularization through subretinal
      administration in the rat.
AB  - This study aimed to investigate uptake dynamics and retinal tolerance of
      phosphorothioate oligonucleotides (PS-oligos) following subretinal injection. A
      fluorescent-labeled PS-oligo (FL-oligo) with random sequence was administered
      into the subretinal space of rat by transsclera-choroid-retinal pigment
      epithelium (RPE) injection at doses of 0.129, 1.29, and 12.9 microg in 2.0 microl
      solution. The uptake dynamics were evaluated by fundus fluorescent photography in
      real time and by fluorescence microscopy using flat mounts and cryosections.
      Immunophenotyping for CD4+, CD8+ cytotoxic lymphocytes, and CD68+ macrophages was
      performed to assess cellular infiltration in the retina. In addition, the FL
      oligo was injected subretinally in a rat model of choroidal neovascularization
      (CNV) for direct delivery into the site of CNV. Subretinal administration of FL
      oligo resulted in both dose-dependent and time-dependent distribution in the
      retina, where it accessed the RPE and all layers of the neuroretina. CD4+, CD8+
      cytotoxic lymphocytes, and CD68+ macrophages were observed at the site of needle
      penetration. However, in areas far from the injection site where the FL-oligo
      appeared strongly, cellular infiltration was absent, and the retinal morphology
      was preserved very well. The FL-oligo was successfully delivered into the site of
      intense laser photocoagulation. It was predominantly localized to the RPE,
      macrophages, and some choroid cells and remained detectable for at least 56 days
      after injection. Our results demonstrate for the first time that subretinal
      injection efficiently introduced PS-oligo into the RPE and neuroretina with an
      acceptable level of safety. Subretinal administration of antiangiogenic
      oligonucleotides may hold great potential for the treatment of CNV.

PMID- 11572603
TI  - PNA beacons for duplex DNA.
AB  - We report here on the hybridization of peptide nucleic acid (PNA)-based molecular
      beacons (MB) directly to duplex DNA sites locally exposed by PNA openers. Two
      stemless PNA beacons were tested, both featuring the same recognition sequence
      and fluorophore-quencher pair (Fluorescein and DABCYL, respectively) but
      differing in arrangement of these groups and net electrostatic charge. It was
      found that one PNA beacon rapidly hybridized, with the aid of openers, to its
      complementary target within duplex DNA at ambient conditions via formation of a
      PD-like loop. In contrast, the other PNA beacon bound more slowly to preopened
      duplex DNA target and only at elevated temperatures, although it readily
      hybridized to single-stranded (ss) DNA target. Besides a higher selectivity of
      hybridization provided by site-specific PNA openers, we expect this approach to
      be very useful in those MB applications when denaturation of the duplex DNA
      analytes is unfavorable or undesirable. Furthermore, we show that PNA beacons are
      advantageous over DNA beacons for analyzing unpurified/nondeproteinized DNA
      samples. This feature of PNA beacons and our innovative hybridization strategy
      may find applications in emerging fluorescent DNA diagnostics.

PMID- 11572604
TI  - PCDD/DF formations by the heterogeneous thermal reactions of phenols and their
      TiO2 photocatalytic degradation by batch-recycle system.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/DFs) formation by the
      thermal reactions of phenols with CuCl2 under oxygen flux were carried out in
      relation to their formation mechanisms. To evaluate the effect of photocatalytic
      degradation of titanium dioxide (TiO2) thin film prepared by the sol-gel method,
      the photocatalysis of PCDD/DFs in acetonitrile/water solution by batch-recycle
      system was conducted. For the thermal reaction system of powder mixtures of 2,4,5
      trichlorophenol (2,4,5-TCP) and CuCl2, the formation rates were 8.1 microg/g
      2,4,5-TCP/min for total PCDD/DFs and 6.9 microg/g-2,4,5-TCP/min for PCDDs, and
      total PCDD/DF rate was higher by approximately 40 fold compared to phenol
      vapor/oxygen/CuCl2 powder system. For the system of 2,4,5-TCP, PCDDs were mainly
      formed via ortho-phenoxyphenols (POP) intermediate by the condensation of 2,4,5
      trichlorophenate. For PCDD/DF photocatalytic degradations, most PCDD congeners
      photodecomposed rapidly and the rates presented more than 70% (as dechlorination
      rates of 76% for PCDDs) at 24 h after irradiation, using PCDD/DFs formed with
      2,4,5-TCP. The rate constants were in the order of 4.8-6.1 x 10(-3) min(-1),
      assuming the pseudo-first-order reactions for their low levels.

PMID- 11572605
TI  - Synthesis of polychlorinated biphenyls (PCBs) using the Suzuki-coupling.
AB  - An improved synthesis of polychlorinated biphenyls (PCBs) utilizing a palladium
      catalyzed cross-coupling reaction (Suzuki-coupling) is described. The coupling of
      (chlorinated) aryl boronic acids 1-3 with bromochlorobenzenes 4 using the
      standard conditions of the Suzuki-coupling gave the desired PCB congeners 5-7 in
      good to excellent yields. The self-coupling product of the aryl boronic acids is
      the major impurity of this reaction. 3,4,5-trichlorophenyl derivatives such as 10
      can be synthesized by coupling of an aryl boronic acid with the corresponding
      bromochloroaniline 8. The approach offers the advantage of high selectivity and
      good yields compared to conventional methods such as the Cadogan reaction and
      allows the use of less toxic starting materials.

PMID- 11572606
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans in plywood combustion gas.
AB  - Polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/DF) levels in plywood
      combustion gas were investigated for the effects of ammonium chloride (NH4Cl) and
      paint. For combustion systems in which neither NH4Cl nor paint were present in
      the plywood samples, total amounts of PCDD/DFs in the combustion gas were in the
      order of 35-529 ng/Nm3, and were higher in the systems with softwood trees than
      broadleaf ones, depending on the Cl concentrations. For the systems with added
      NH4Cl and no paint, and those without NH4Cl but were painted, higher PCDD/ DF
      rates were observed at combustion temperatures of 270 degrees C and 500 degrees
      C, respectively. However, for the systems with both NH4Cl and paint, their
      amounts in the range of 0.6-13 ng/Nm3 were the lowest in all systems. The PCDD/DF
      abundance profiles were similar to their patterns in pentachlorophenol (PCP).
      Furthermore, it was found that the 2,3,7,8-chlorine substituted penta- and hexa
      CDDs contributed more than other 2,3,7,8-chlorine substitutes to toxicity
      equivalency (TEQ).

PMID- 11572607
TI  - Quantitative structure-property relationships (QSPRs) on direct photolysis of
      PCDDs.
AB  - By the use of partial least squares (PLS) method and 27 quantum chemical
      descriptors computed by PM3 Hamiltonian, a statistically significant QSPR were
      obtained for direct photolysis quantum yields (Y) of selected Polychlorinated
      dibenzo-p-dioxins (PCDDs). The QSPR can be used for prediction. The direct
      photolysis quantum yields of the PCDDs are dependent on the number of chlorine
      atoms bonded with the parent structures, the character of the carbonoxygen bonds,
      and molecular polarity. Increasing bulkness and polarity of PCDDs lead to
      decrease of log Y values. Increasing the frontier molecular orbital energies
      (Elumo and Ehomo) and heat of formation (HOF) values leads to increase of log Y
      values.

PMID- 11572608
TI  - Atmospheric fate and transport of dioxins: local impacts.
AB  - We conducted model simulations of the atmospheric fate and transport of PCDD/F to
      assess the fraction of emitted PCDD/F that would deposit within 100 km from the
      source. We considered eight major categories of PCDD/F emission sources and six
      different locations, to cover a wide range of source characteristics, PCDD/F
      congener profiles and particle size distributions, meteorological conditions and
      terrain configurations. These results suggest that for sources that have tall
      stacks and/or high plume rise (e.g., copper smelters, cement kilns, sinter
      plants), only a small fraction of PCDD/F emissions is deposited locally
      (typically, less than 10% within 100 km). Other source categories such as
      municipal solid waste incinerators, medical waste incinerators and diesel trucks
      lead to a greater fraction of PCDD/F being deposited locally; nevertheless, the
      majority of their PCDD/F emissions tends to be transported beyond 100 km.
      Although local impacts may need to be addressed for these latter source
      categories, it appears that the long-range potential impacts of PCDD/F need to be
      addressed for all source categories. Sensitivity studies were conducted to
      investigate the effect of various key model inputs on simulation results. These
      studies suggest that an advanced atmospheric dispersion model should be used for
      cases where PCDD/F emissions may present some local concerns because the results
      are very sensitive to the treatment of dispersion. Also, it is essential to
      obtain accurate characterizations of the particle size distribution of
      particulate PCDD/F because the dry deposition flux is very sensitive to the
      particle size distribution.

PMID- 11572609
TI  - Congener-specific characterization of PCDDs/PCDFs in atmospheric deposition:
      comparison of profiles among deposition, source, and environmental sink.
AB  - In order to examine the input of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDDs/PCDFs) from various airborne sources to environmental sinks,
      the atmospheric deposition of congener-specific PCDDs/PCDFs was investigated.
      Homologue and congener profiles of atmospheric depositions were compared with
      those of sources and environmental sinks to identify the relationship among
      atmospheric depositions, sources, and environmental sinks. Moreover, factor
      analysis was used to detect similarities, differences, and relationships of the
      variations in deposition fluxes among congeners within the same and different
      homologues. The results showed that the congener profiles of the atmospheric
      depositions were primarily determined by those of combustion emissions. Several
      congeners in some specific samples showed higher proportions within each
      homologue compared with representative depositions. This result can be partly
      explained by the influence of impurities in herbicides, 1,3,5-trichloro-2-(4
      nitrophenoxy) benzene (CNP) and pentachlorophenol (PCP). The congener profiles of
      combustion emissions, representative depositions, and urban soils were very
      similar although their homologue profiles varied. This implied that PCDDs/PCDFs
      in the urban soils originate from the deposition of combustion emissions and that
      all congeners within each homologue behave identically in air and soil. Although
      the congener profiles of the representative depositions were different from those
      of the sediments in Tokyo Bay and the soil of a paddy field, the combination of
      congener profiles of the representative depositions and of the impurities in
      herbicides. CNP and PCP, can explain the congener profiles of the sediments and
      the paddy field. This study showed that congener-specific data are useful for
      source identification.

PMID- 11572610
TI  - Vitamin and thyroid status in arctic grayling (Thymallus arcticus) exposed to
      doses of 3,3',4,4'-tetrachlorobiphenyl that induce the phase I enzyme system.
AB  - Induction of phase I biotransformation enzymes is recognized as a hallmark
      response in fish exposed to coplanar PCBs. Depletions of vitamins A and E and
      disrupted thyroid hormone and glandular structure secondary to this induction
      have not yet been examined in an arctic fish species. Arctic grayling were
      exposed to a single oral dose of 0 (control), 10, 100 or 1000 ng 3,3',4,4'
      tetrachlorobiphenyl (TCB) g(-1) bodyweight, a contaminant found in most arctic
      fish. After 30 and 90 days of exposure, TCB concentrations in tissues, hepatic
      phase I activity (as ethoxyresorufin-O-deethylase (EROD)), plasma and tissue
      vitamin A and E concentrations, plasma thyroid hormone levels and thyroid
      glandular structure were examined. Total plasma osmolality, as an indicator of
      overall fish health was also monitored. TCB recovery in tissues was low and
      extremely variable, making comparisons between intended dose groups
      inappropriate. Therefore, correlation analysis between actual recovered TCB
      concentrations and biochemical responses was employed. Hepatic EROD activity
      correlated strongly with liver TCB concentrations. Liver concentrations of
      vitamin A were altered as a function of TCB concentrations and EROD activity, but
      plasma vitamin A status was not affected. Vitamin E was depleted by TCB
      accumulation in blood and EROD induction in liver of males only at 90 days
      postexposure. Thyroid hormones status and glandular structure were not affected
      by the short duration TCB exposures used in this experiment. TCB concentrations
      were correlated with an elevation in plasma osmolality. Results from this
      experiment indicate that the vitamin status and osmoregulation of arctic grayling
      exposed to TCB can be compromised. Further studies of field populations exposed
      to this type of contaminant are warranted.

PMID- 11572611
TI  - Enhancement in fecal excretion of dioxin isomer in mice by several dietary
      fibers.
AB  - The effect of increased nutrients (protein, lipid, vitamins and minerals) on
      dioxin-induced toxic manifestations such as immune suppression, hepatic
      hypertrophy, splenic atrophy and enzyme induction was investigated in mice after
      oral administration of 1,2,3,4,7,8-HxCDD (HxCDD) as one of a representative
      compound of dioxin isomers. Consequently, it appeared that increased minerals and
      vitamins in the diet prevented immune suppression by HxCDD. In addition, to
      clarify the additive effect of nutrients and the ability to hasten the excretion
      of dioxins by dietary fiber, the adsorbing of dioxins by 16 dietary fibers was
      investigated by in vitro experiment. Among 16 dietary fibers, locust bean gum,
      pectin, alginic acid, guar gum, chitin and cellulose were effective in binding
      dioxin isomers. These dietary fibers also enhanced the fecal excretion of HxCDD
      in mice.

PMID- 11572612
TI  - The influence of dietary concentration on the absorption and excretion of
      persistent lipophilic organic pollutants in the human intestinal tract.
AB  - The gastrointestinal exchange of polychlorinated biphenyls (PCBs), dibenzo-p
      dioxins, and dibenzofurans (PCDD/Fs) as well as hexachlorobenzene was measured in
      five volunteers. The dietary intake and the fecal excretion of the chemicals were
      quantified and the net absorption/net excretion was calculated as the difference
      between these two fluxes. Experiments were conducted using an elevated dietary
      intake and a reduced dietary intake of chemical, and the results were compared
      with the absorption during normal dietary intake. The net absorption varied
      widely with the dietary intake for those compounds which bioaccumulate in humans;
      high dietary intake of chemical resulted in absorption approaching 100% of
      intake, while low dietary intake resulted in a net excretion several times
      greater than the dietary intake. In contrast to net absorption, the chemical flux
      in the feces was largely independent of the dietary intake of chemical for a
      given individual. Good agreement was found between the feces/blood distribution
      coefficients measured in this study and in a study with contaminated workers
      whose blood concentrations were several orders of magnitude higher, indicating
      that fecal excretion of chemical is linearly proportional to the blood
      concentration. The results suggest that gastrointestinal exchange can be viewed
      as two processes operating simultaneously: absorption of contaminant from the
      diet, and excretion of contaminant from the body's reservoirs via the feces. By
      subtracting that component of the fecal flux originating from the body, the
      maximum dietary absorption could be calculated. This was >95% for most of the
      compounds, decreasing to a minimum of 50-60% for the octachlorinated dioxins and
      furans. The maximum dietary absorption showed a Kow dependency consistent with
      the two film model of gastrointestinal absorption of persistent organic
      chemicals.

PMID- 11572613
TI  - Reliable QSAR for estimating Koc for persistent organic pollutants: correlation
      with molecular connectivity indices.
AB  - Several recent studies have shown that n-octanol/water partition coefficients may
      not be a good predictor for estimating soil sorption coefficients of persistent
      organic pollutants (POPs), defined here as chemicals with log Kow greater than 5.
      Thus, an alternative QSAR model was developed that seems to provide reliable
      estimates for the soil sorption coefficients of persistent organic pollutants.
      This model is based on a set of calculated molecular connectivity indices and
      evaluated soil sorption data for 18 POPs. The chemical's size and shape,
      quantified by 1chi, 3chiC and 4chiC(v) indices, have a dominant effect on the
      soil sorption process of POPs. The developed QSAR model was rationalized in terms
      of potential hydrophobic interactions between persistent organic pollutants and
      soil organic matrix. Its high predictive power has been verified by an extensive
      internal and external validation procedure.

PMID- 11572614
TI  - Correlation of gas chromatographic properties of chlorobenzenes and
      polychlorinated biphenyls with the occurrence of reductive dechlorination by
      untamed microorganisms.
AB  - To understand the dechlorination ability of chlorobenzenes (CBs) and
      polychlorinated biphenyls (PCBs) by untamed microorganisms under anaerobic
      condition and to correlate gas chromatographic properties with the occurrence of
      reductive dechlorination, introduction of CBs and PCBs in the culture medium
      inoculated with microorganisms from sludge and sediment, respectively, were
      performed. Three kinds of culture media preparing from sludge, river water and a
      synthetic medium were used in the experiments. HCB was degraded to 1,3,5
      trichlorobenzene (1,3,5-TCB) and 1,3-dichlorobenzene (1,3-DCB) in both sludge
      medium and synthetic medium with inoculated microorganisms. Three PCB congeners
      including 2,3,4-, 3,4,5- and 2,3,4,5-CBp (chlorinated biphenyl) were not found to
      be dechlorinated in the river water medium with inoculation culture but to be
      dechlorinated in the synthetic medium. MNDO methodology was used to compute
      theoretical dechlorination reaction heats and GC-ECD techniques were used to
      estimate chromatographic data of CB and PCB congeners. Both CB and PCB congeners
      showed that dechlorination by untamed microorganisms under anaerobic mixed
      cultures were more likely to occur when larger amounts of energy were released
      and greater deltaln RRT value between the parent congener and the daughter
      product was observed. Deltaln RRT provided a more precise information on the
      singularity of PCBs ortho-dechlorination in an aspect of thermodynamic favorable
      rule.

PMID- 11572615
TI  - Age-related changes in fear, sociality and pecking behaviours in two strains of
      laying hen.
AB  - 1. Two lines of commercial hybrid layers (Tetra and ISA Brown) were reared from
      hatch to 30 weeks of age in groups of 8. The objectives of the experiment were to
      evaluate the significance of the different selection practices involved in the
      development of the lines and to assess the potential association between selected
      behavioural states and the potential for feather damage and cannibalism. 2.
      Behavioural tests related to fear (tonic immobility, novel object, open field),
      sociality (runway, proximity in the home pen) and pecking (feather bunch and
      focal observations of inter-bird and environmental pecking) were conducted at 0
      to 2, 5 to 7, 12 to 14, 19 to 21 and 29 to 31 weeks of age. Scan sampling of
      general behaviour was also conducted at these ages. 3. Underlying sociality was
      greater in Tetras than in ISA Brown hens. 4. There were no apparent overall
      strain differences in fearfulness although ISA Brown hens showed significantly
      longer tonic immobility fear reactions than Tetras at 31 weeks of age. 5. ISA
      Brown hens gave and received more gentle pecks than Tetra hens whereas preening
      was commoner among Tetras. There were no strain differences in the number of
      pecks at litter or food. 6. As birds aged they showed less avoidance of novel
      objects and Tetras, though not ISA Browns, showed progressively shorter tonic
      immobility responses. Birds of both strains spent less time resting, more
      foraging (pecking and scratching) and pecked more at the feather bunch at older
      ages. 7. Measures taken in the TI, open field, runway (social affiliation) and
      feather bunch tests were stable over time whereas focal observations of pecking
      at hens and the environment were not. 8. Factor Analysis showed that 3 factors
      defined by the novel object test, environmental pecking and pecking ata feather
      bunch explained most of the variation in the correlation matrix between summary
      measures for the 8 behavioural traits.

PMID- 11572616
TI  - Welfare assessment of modified rearing programmes for broiler breeders.
AB  - 1. Female broiler breeders were fed ad libitum or a restricted quantity of food
      to achieve either a recommended body weight curve or a modified (linear) growth
      curve that allowed more generous feeding between 6 and 15 weeks of age. The birds
      were fed a ration containing either a normal or low concentration of crude
      protein. The welfare of the birds was assessed using a profile of indices of
      welfare at 6, 12, 18 and 24 weeks of age. 2. The low-protein ration decreased the
      body weight of birds fed ad libitum and restricted birds were fed substantially
      more of the low-protein ration to meet target body weights from 3 to 14 weeks of
      age. 3. The modified restricted rearing programme did not have an effect on
      indices of welfare. 4. Water intakes and plasma corticosterone concentrations
      were lower in restricted birds fed the low-protein ration and they spent more
      time resting, and less time spot-pecking, than birds fed the high-protein ration.
      5. Birds fed ad libitum on both rations spent more time resting and less time
      foraging, drinking and spot-pecking than food restricted birds and were more
      fearful than restricted birds at 6, 12 and 18 weeks of age. 6. The
      heterophil:lymphocyte ratio in restricted birds was higher at 6 weeks and lower
      at 24 weeks compared with birds fed ad libitum. Humoral immunity was lower at 6
      weeks of age in birds fed ad libitum and was similar at other ages. Cell-mediated
      immunity was similar among all treatments. 7. Plasma corticosterone
      concentrations were higher in restricted birds compared with birds fed ad
      libitum. Plasma creatine kinase activity was higher in birds fed ad libitum at 6,
      12 and 18 weeks of age. Alkaline phosphatase and lactate dehydrogenase activity
      were higher whereas AST was lower in restricted birds compared with those fed ad
      libitum. 8. There was no evidence to support the use of low protein rations or
      linear growth curves to improve welfare in restricted broiler breeder females.

PMID- 11572617
TI  - Behaviour of domestic ducks exposed to mobile predator stimuli. 1. Flock
      responses.
AB  - 1. Small flocks of ducks (Anasplatyrhynchos domesticus) were exposed to two
      stimuli, a small mobile vehicle and a walking human, to investigate their flight
      responses. 2. Experiment 1. Flocks were herded around an annular arena by each
      stimulus at 0.5 ms(-1) and the flight distance between the stimulus and the
      centre of the flock, and individual positions within the flock were recorded
      every 10 s. Flocks maintained a significantly longer distance from the human (6.0
      m) than the vehicle (5.1 m) and usually did not maintain visual contact with
      either stimulus. Significant consistency in individual positions within the flock
      was found within and between trials. 3. Experiment 2. Flocks were exposed to each
      stimulus which approached them as they were feeding in a circular arena. The
      latencies for cessation and resumption of feeding were recorded and the paths
      followed by the flocks described. Ducks showed a significantly shorter latency to
      cease feeding in response to the human (4.9 s) compared with the vehicle (6.9 s).
      4. Domestic ducks apparently perceive an approaching human as a greater threat
      than a small vehicle. The findings are discussed in relation to the development
      of herding robots.

PMID- 11572618
TI  - Behaviour of domestic ducks exposed to mobile predator stimuli. 2. The
      association of individual duckling attributes with relative position in a flock.
AB  - 1. We investigated whether an individual duckling's (Anas platyrhynchos
      domesticus) attributes were associated with its response to an approaching human
      when it was a member of one of three flocks of 12. 2. Each individual was scored
      according to its response to (i) an approaching human when alone and feeding,
      (ii) a taxidermist's model fox when alone and feeding, and (iii) an approaching
      human when alone in a 9 m annulus, and its nearest neighbour distance in the home
      pen, competitiveness for food in a series of paired encounters, running ability
      and physical characteristics. 3. Each flock was herded around a 7 m diameter
      annulus in separate trials by a human walking at 0.5ms(-1). The distance
      maintained by each duckling from the human, and hence its relative flock
      position, was calculated. 4. Individual flight distance maintained from an
      approaching human when alone in an annulus was the attribute that predicted
      distance maintained from an approaching human when part of a flock. 5. Some
      ducklings had reduced average distances from an approaching human when they were
      in a flock compared to when they were tested alone, and inter-individual
      variation in distance from the human was greatly reduced when birds were part of
      a flock.

PMID- 11572619
TI  - Effects of ambient temperature and restricted feeding on the growth of feathers
      in growing turkeys.
AB  - 1. Male turkeys were reared to 6 weeks of age at 15 degrees C and 26 degrees C
      and fed ad libitum or restricted to 0.5 of the body weight of birds fed ad
      libitum. Basal metabolic rate was determined by indirect calorimetry at an
      ambient temperature of 20 degrees C. 2. Turkeys at 15 degrees C were lighter than
      those kept at 26 degrees C. Feather lengths and weight were similar in both
      groups. Fasting heat production corrected for both metabolic body size and
      activity was greater in turkeys reared at 15 degrees C than those at 26 degrees
      C. 3. Cranial breast feathers were significantly longer in restricted birds than
      in those fed ad libitum in contrast to a proportional decrease in the lengths of
      other feathers of 0.1 to 0.3. Feather weight as a proportion of body weight was
      0.072 in restricted turkeys compared with 0.046 in birds fed ad libitum. There
      was no difference in basal metabolic rate between ad libitum and restricted
      turkeys. 4. It was concluded that feather growth was maintained in preference to
      body and muscle growth and that rearing birds at 15 degrees C did not improve
      breast feather cover. It is suggested that the growth of breast feathers in
      turkeys fed ad libitum is impaired.

PMID- 11572620
TI  - Effect of dietary probiotic on performance and humoral immune response in layer
      hens.
AB  - 1. The effects of dietary supplementation of a commercial probiotic (Protexin) on
      daily feed consumption, egg yield, egg weight, food conversion ratio and humoral
      immune response in layer hens were investigated. In 7 replicates, a total of 280
      40-week-old layers were given diets containing either 0, 250, 500 or 750 parts
      per million (ppm) for 90 d. 2. When compared with the controls, the food
      consumption, food conversion ratio and the proportions of damaged eggs were lower
      in the group consuming 500 ppm probiotic (P<0.05). 3. There was no significant
      difference between the controls and the groups receiving 250 and 750 ppm
      probiotic in food consumption, food conversion ratio and proportion of damaged
      eggs. Similarly, the egg yield, egg weight, specific gravity, and peripheral
      immune response showed no statistically significant differences between the
      groups.

PMID- 11572621
TI  - Post mortem muscle metabolism and meat quality in three genetic types of turkey.
AB  - 1. A standard (FG, fast-growing), a black local or 'label', type (SG, slow
      growing) turkey line, and the crossbreed between these two lines were compared
      for muscle post-mortem metabolism and related meat quality traits. 2. Ninety male
      turkeys (30 of each genetic type) were raised under the same experimental
      conditions until slaughter at 16 weeks of age. 3. Live weights at 16 weeks of age
      differed significantly (7.8, 6.0 and 4.2 kg, for the FG, crossbred and SG lines,
      respectively). Collagen content of Pectoralis superficialis (PS) muscle was
      higher in SG birds than in the other two types. 4. The rate of post-mortem
      glycogen depletion and lactate accumulation in PS and Ilio tibialis (IT) muscles
      were similar in the 3 lines, as were the rate and extent of post-mortem pH fall
      in PS muscle. In IT muscle, however, SG birds showed a slight but significantly
      faster pH decline. 5. Colour measurements indicated a paler breast muscle and a
      higher degree of myoglobin oxidation in SG birds at 24 h post mortem, than in
      both other lines. But these differences had disappeared after 4 and 7 d post
      mortem 6. SG birds showed higher drip loss and instrumentally-assessed toughness
      in breast muscle, compared with crossbred and FG birds. FG birds, however, had
      the lowest yield of breast meat after curing-cooking. 7. No marked differences in
      post-mortem metabolism were found between the three lines. However, differences
      in water-holding capacity of fresh and cured-cooked meat suggest that factors
      other than the rate and extent of post-mortem pH fall may contribute to the
      respective characteristics of these lines.

PMID- 11572622
TI  - Effect of genotype, sex and rearing temperature on carcase and meat quality of
      guinea fowl.
AB  - 1. The aim of our study was to analyse the effect of genotype (label and
      standard), sex and rearing temperature (simulating daily outdoor in the summer or
      winter) on the carcase and meat quality of guinea fowl. Using 20 animals per
      treatment, slaughtered at 96 d of age we measured the breast angle and the
      thickness of the skin on the wing membrane. Carcases were weighed and cut into
      parts according to a standardised procedure to determine the percentages of
      abdominal fat, breasts, wings and thighs with shanks. 2. At slaughter, standard
      guinea fowl were heavier than label guinea fowl and for both genotypes, the
      females were heavier than the males (+5.6%). The mean value of breast angle was
      85 degrees. This value was significantly higher for the standard guinea fowls and
      for the females of both genotypes compared with males. Thus, female carcases,
      particularly standard females, were more compact. The skin was thicker for the
      standard guinea fowls (0.84 mm vs 0.77 mm) which could be due to more
      subcutaneous fat. 3. Carcase yield was higher for the males (68.7% vs 68.2%). The
      percentage of abdominal fat was higher for the standard guinea fowls (2.8% vs
      2.4%) and for the females of both genotypes compared with males. The label guinea
      fowls had higher yields of breasts and thighs with shanks. For both lines, the
      breast and thigh meat of females was judged more tender and less stringy. 4. Low
      rearing temperature decreased growth performance but had no significant effect on
      carcase quality.

PMID- 11572623
TI  - The incorporation of whole grain into pelleted broiler chicken diets: production
      and physiological responses.
AB  - 1. Pelleted diets, incorporating whole or ground triticale or wheat in the
      pellets, were fed to broiler chickens and the performance, gastro-intestinal
      development and health of those chickens recorded. 2. The use of whole triticale
      in the pelleted food produced similar bodyweight responses to when ground
      triticale was incorporated in the food. Food conversion efficiency was enhanced
      when whole triticale was used compared to ground triticale and was similar to
      when an exogenous enzyme was added to the ground triticale diet. The
      incorporation of whole wheat into the pelleted food produced similar production
      responses to the use of ground wheat. 3. The gastro-intestinal development of the
      birds was greater when they were fed the whole grain diet as gizzard weights were
      increased by the incorporation of whole grain into the diet. Gastro-intestinal
      development was thought to be related to the presence of large fibre particles in
      the food. 4. Proventricular dilatation and mortality due to ascites were reduced
      by feeding pelleted diets containing whole grain, which was possibly related to
      the early development of the gastro-intestinal tract relative to total body
      development. 5. It is suggested that the current use of exogenous enzyme
      additions to broiler diets may be reduced by incorporating whole grain into
      pelleted diets for broiler chickens.

PMID- 11572624
TI  - The response of broilers to the feeding of mash or pelleted diets containing
      maize of varying particle sizes.
AB  - 1. The effects of maize particle size and steam pelleting on growth and nutrient
      utilisation were studied with broiler chicks. 2. The presence or absence of 10
      microg/kg of 1,25 dihydroxycholecalciferol in diets adequate or deficient in
      phosphorus was also investigated. Food efficiency was superior with the fine
      maize diets but calcium retention and phytate phosphorus retention were greatest
      with the coarse maize diets. Pelleting improved food efficiency and growth in
      both experiments while phytate phosphorus utilisation was decreased. 3. Addition
      of 1,25-dihydroxycholecalciferol to the diet increased 16-d body weight, bone
      ash, plasma dialysable phosphorus and retentions of total phosphorus and phytate
      phosphorus while decreasing phosphorus deficiency rickets and tibial
      dyschondroplasia. 4. There were significant interactions between maize particle
      size and food form. The improvement in calcium retention observed with the coarse
      maize diets was reduced when the diets were pelleted. When fed as a mash, coarse
      maize diets resulted in increased plasma dialysable phosphorus levels but when
      the diet was pelleted this response was eliminated. 5. There was also a
      significant interaction between particle size and phosphorus concentration in
      that chicks given diets deficient in phosphorus had improved bone ash when fed
      coarse maize as compared to fine maize. However, this response was eliminated
      when the diets were adequate in phosphorus. 6. In one experiment, fine maize
      diets had higher metabolisable energy values and there was a significant
      interaction between maize particle size and food form as pelleting improved the
      metabolisable energy value of coarse maize diets but not fine maize diets. In
      another experiment only pelleting of the factors studied improved the
      metabolisable energy value of the diets.

PMID- 11572625
TI  - The effects of adding xylanase, vitamin C and copper sulphate to wheat-based
      diets on broiler performance.
AB  - 1. The study used a 3 x 3 factorial design to evaluate the effects of 3 additives
      (none; vitamin C [250 mg/kg]; copper sulphate [250 mg/kg]) and 3 enzyme additions
      (none; Avizyme 1300 [Finnfeeds Ltd, 1 g/kg in food]; Avizyme 1310 [liquid spray,
      post-pelleting, 0.5 g/kg]). All experimental diets were mixed, heat-conditioned
      (80 degrees C for 2 min) and pelleted. Copper sulphate (diets NCu; DCu; LCu) and
      Avizyme 1300 (diets DN; DC; DCu) were added during mixing. Vitamin C was sprayed
      at 10 ml per kg (diets NC; DC; LC) and the liquid enzyme was diluted 20-fold and
      sprayed at the same rate (diets LN; LC; LCu), post-pelleting. 2. Additive or
      enzyme addition did not significantly affect DM intake or liveweight gain (LWG).
      Enzyme addition improved gain:food (P=0.014), AME:GE (P<0.001), ileal apparent
      digestibility of DM (P=0.008) and starch (P<0.001), faecal apparent digestibility
      of starch, crude fat and NDF (P=0.008; <0.001; <0.001 respectively) and reduced
      in vivo viscosity (P<0.001). 3. Copper sulphate addition depressed gain:food
      (P=0.047), AME:GE (P=0.002), ileal apparent digestibility of starch (P<0.001) and
      faecal apparent digestibility of starch (P=0.003) and crude fat (P<0.001) due to
      a negative additive x enzyme interaction when copper sulphate and dry enzyme were
      included together. 4. Vitamin C decreased in vivo viscosity by 20% but failed to
      have any effect on performance. Both enzyme forms gave similar improvements in
      performance in the absence of copper sulphate.

PMID- 11572626
TI  - Insulin administration suppresses an increase in insulin-like growth factor
      binding protein-2 gene expression stimulated by fasting in the chicken.
AB  - 1. We examined the changes in plasma IGF-I concentration and tissue IGFBP-2 gene
      expression of young fasted chickens refed a commercial diet or administered
      bovine insulin intravenously. 2. Plasma IGF-I concentration was decreased by
      fasting for 2 d. Although plasma IGF-I concentration was increased by refeeding,
      it didn't recover to the level of chickens fed a commercial diet ad libitum. 3.
      Insulin administration lowered plasma IGF-I concentration compared to other
      groups. 4. Hepatic IGFBP-2 mRNA was increased by fasting for 2 d and decreased by
      refeeding for 6 h. Insulin administration also decreased hepatic IGFBP-2 gene
      expression stimulated by fasting to the level of refed chickens. 5. IGFBP-2 mRNA
      in the gizzard was increased by fasting for 2 d and tended to decrease after
      refeeding for 6 h. Insulin administration decreased gizzard IGFBP-2 gene
      expression to less than that in refed chickens. 6. There was no between-treatment
      difference in IGFBP-2 mRNA in the brain and kidney. 7. These results suggest that
      the changes in IGFBP-2 gene expression in the liver and gizzard by fasting and
      refeeding might be partly regulated by the alteration in plasma insulin
      concentration.

PMID- 11572627
TI  - Body and intestinal growth of broiler chicks on a commercial starter diet. 1.
      Intestinal weight and mucosal development.
AB  - 1. A study was conducted on the pattern of development of the intestinal mucosa
      of the Steggles x Ross (F1) strain of broiler chickens reared on a commercial
      starter diet. The mechanisms underlying the structural changes were also
      assessed. 2. In relation to body weight, small intestinal weight peaked at 7 d of
      age and declined subsequently. There was also a reduction in the relative weights
      of the gizzard and yolk sac with age. The length of the small intestine and its
      regions increased with age. 3. Crypt depth increased with age in the duodenum and
      jejunum while villus height increased significantly with age in all three regions
      of the small intestine. There were also significant changes in apparent villus
      surface area in the three regions, while interactions between age and intestinal
      region were significant in the case of crypt depth and villus height. 4. There
      were significant differences between the age groups in the mucosal protein
      content of jejunal and ileal homogenates, both tending to peak at 7 d of age. The
      DNA content of the intestinal mucosa declined with age in the three regions of
      the small intestine. While there was an increase in RNA content in the duodenum
      and ileum, there was a reduction in the jejunum. 5. Protein: DNA ratio increased
      between hatch and 21 d of age in all intestinal regions. Protein: RNA ratio
      decreased with age in the duodenum and ileum but increased in the jejunum. There
      were significant increases in RNA: DNA ratio in the duodenum and ileum but no
      changes were observed in the jejunum. The interactions between age and intestinal
      region were significant for all biochemical indices assessed. 6. At all ages,
      enterocyte proliferation at the jejunum was completed and quantifiable within 1 h
      of administration of 5-bromo-2'-deoxyuridine (BrDU). Subsequent assessment
      revealed an increase in crypt column count and number of BrDU-labelled cells. The
      rate of cell migration increased with age while there was a decline in the
      distance migrated in proportion to mucosal depth. The estimated life-span of
      enterocytes and time spent by enterocytes in the crypt varied with age. In d-old
      and 7-d-old chicks, migration was complete or nearly complete within 96 h of cell
      birth. 7. Although the intestinal mucosa of the strain was structurally developed
      at hatch, there was much change in structure with age, especially over the first
      7 d post hatch. The rate of development was most rapid in the jejunum but the
      other regions are also important, on account of villus height or relative length
      of the region.

PMID- 11572628
TI  - Body and intestinal growth of broiler chicks on a commercial starter diet. 2.
      Development and characteristics of intestinal enzymes.
AB  - 1. Investigations were conducted into the development of intestinal enzyme
      function in broiler chickens on a commercial starter diet. The differences
      between intestinal regions and localisation of enzymes on the villus were
      assessed. 2. The specific activity of maltase, sucrase, aminopeptidase N (APN)
      and alkaline phosphatase (AP) at all intestinal sites decreased with age. There
      were also variations between intestinal sites although this variation depended on
      age. The specific activity of maltase was higher than that of the other enzymes
      examined, regardless of age and intestinal site. The total activities of the
      enzymes also increased with age at all intestinal sites. 3. Results of the
      localisation of enzymes on the crypt: villus axis showed that activity was
      expressed over a large proportion of the villus. There was an increase in the
      total villus activity of alpha-glucosidase (AG), APN and AP with age. Activity
      per unit villus surface area was similar between ages, except for jejunal AP. At
      hatch enzyme activity was expressed over 44.1, 55.8 and 63.3% of villus height in
      the duodenum, jejunum and ileum, respectively. At 21 d of age, corresponding
      values were 68.7, 65.6 and 77.2%. The point of peak activity from the crypt:
      villus junction increased with age. In the jejunum, most enterocytes were capable
      of secreting active enzymes within 1 h of formation. Cells maintained their
      secretory capabilities until they were more than 60 h old in the case of AG. 4.
      Although the specific activities of the enzymes were maximal at hatch, the
      digestive capacity of older birds may be sustained by an increase in total enzyme
      activity brought about by increased surface area. The pattern of enzyme activity
      along the gastrointestional tract (GIT) and crypt: villus axis is similar to that
      reported for some mammalian species.

PMID- 11572629
TI  - Body and intestinal growth of broiler chicks on a commercial starter diet. 3.
      Development and characteristics of tryptophan transport.
AB  - 1. A study was conducted to characterise the development of amino acid transport
      in broiler chicks, using L-tryptophan as a model. The chicks were maintained on a
      broiler starter diet between hatch and 21 d of age. 2. There was a significant
      reduction in the rate of uptake of 0.04 mM L-tryptophan with age in both the
      jejunum and ileum. Uptake was enhanced in the presence of 50 mM sodium chloride
      to different degrees depending on age and intestinal site. At both intestinal
      sites, uptake capacity increased with age while there was a reduction in uptake
      efficiency with age. 3. At a concentration of 25 mM, both sodium chloride and
      potasium chloride increased uptake by ileal brush-border membrane vesicles (BBMV)
      of 7-d-old chicks but uptake was reduced when potassium chloride was included at
      a concentration of 50 mM. In the presence of valinomycin, uptake by jejunal BBMV
      was stimulated by 25 mM sodium chloride. In the presence of both sodium chloride
      and potassium chloride and in the absence of valinomycin, uptake was increased by
      42.6% but this was reduced to 23.4% when the ionophore was included in the
      buffer. 4. The Na+-independent uptake of L-tryptophan into jejunal vesicles of 21
      d-old chicks was lower in the presence of D-tryptophan than in the presence of 2
      aminobicyclo-[2,2,1]-heptane-2-carboxylic acid (BCH). The inclusion of BCH in the
      incubation medium at low concentrations significantly enhanced the uptake of 0.04
      mM L-tryptophan by jejunal BBMV. 5. At similar concentration (0.04 mM) to L
      tryptophan, lysine, methionine and alanine in the presence of Na+ also stimulated
      L-tryptophan uptake. The uptake of L-tryptophan was reduced at a higher
      concentration, 25 mM, of these amino acids. 6. The study revealed a decline in
      rate of amino acid uptake and an increase in total uptake capacity with age.
      Tryptophan uptake was both Na+-independent and dependent, and occurred more in
      the ileum than in the jejunum. The uptake of L-tryptophan depended on the
      concentration of other amino acids and other factors in the diet and digesta.

PMID- 11572630
TI  - Effect of exogenous oestradiol and lighting regime on age at first egg in
      domestic pullets.
AB  - 1. Groups of ISA Brown pullets were transferred from 8- to 16-h photoperiods at
      34, 44 or 54 d. In each group, 12 birds were injected on alternate days over a 12
      d period starting 6 d before the change in photoperiod with beta-oestradiol-3
      benzoate (1 mg/kg body weight) or with arachis oil vehicle (controls). Short-day
      controls were similarly injected from 28 to 40 d. Long-day (16 h) controls were
      also included in the trial but were not injected. Age at first egg (AFE) was
      recorded and plasma luteinising hormone (LH) concentrations were measured around
      the time of oestradiol treatment. 2. Mean AFE for birds photostimulated at 34 d
      was not significantly different from short-day controls. Birds photostimulated at
      44 and 54 d matured at similar ages but 3 weeks earlier than short-day controls
      (P<0.05). 3. There was a tendency for oestradiol to advance AFE for birds
      photostimulated at 34 d (P=0.15) but to delay AFE following photostimulation at
      44 d (P=0.23). Oestradiol significantly delayed AFE for the birds photostimulated
      at 54 d (P=0.01). 4. Plasma LH levels during 6 d of oestradiol injection but
      before transfer from 8- to 16-h photoperiods tended to fall between 28 and 34 d,
      were relatively constant between 38 and 44 d, but declined significantly between
      48 and 54 d. Following photostimulation at 34 d, increases in plasma LH levels
      for oestradiol-injected birds were significantly greater than for controls.
      Oestradiol treatment had no significant effect on changes in plasma LH
      concentrations after photostimulation at 44 or 54 d. 5. This trial confirms
      previous work showing that pullets are unresponsive to photostimulation before 6
      weeks of age. It also demonstrates that raising circulating oestrogen levels by
      injecting 0.5 mg/kg oestradiol benzoate on alternate days enhances the LH
      response to photostimulation at 34-d, but only very slightly sensitises a 34-d
      old bird to an increase in photoperiod which, 10 d later, is capable of advancing
      AFE in control birds by 24 d. Increased circulating oestrogen might be a factor
      which allows pullets to advance AFE in response to an increase in daylength.

PMID- 11572631
TI  - Individual variation in corticosterone secretion in laying hens.
AB  - 1. Plasma corticosterone responses to a handling and isolation stressor were
      measured in laying hens once, before two groups were mixed into a single larger
      group, and again after the groups were mixed. Hens were bled before the stressor
      was applied and within 3 min of removal from groups (0 min sample), and again 15
      and 45 min later 2. Social interactions were recorded throughout the experiment
      using continuous, all-occurrences sampling during group observations and the
      social rank index of each hen was calculated. 3. Plasma corticosterone was low
      immediately after birds were first picked up and sampled on each occasion, and
      rose to a peak after repeated handling, 15 min later. It then declined and was
      almost back to basal levels 40 min after first handling. 4. Corticosterone
      responses were greater 6 d before mixing (first day of sampling) than they were
      1, 7 or 21 d after mixing. Corticosterone concentrations and responses were not
      elevated 1 d after the two groups of hens were mixed. 5. Variation in
      corticosterone concentrations and responses within and between hens was
      quantified by calculating coefficients of variation of corticosterone
      concentrations and areas under corticosterone response curves. Variation tended
      to be less within than between hens. 6. There was a transient increase in
      aggressive interactions immediately after mixing. One bird was clearly dominant
      in each observed dyadic interaction and hierarchies tended to strong linearity in
      all groups. Social rank was not related to corticosterone concentrations or
      responses. 7. Area under the corticosterone response curve can be used to compare
      differences between and within laying hens in their responsiveness to a handling
      and isolation stressor.

PMID- 11572632
TI  - Immunity to polyoma virus infection and tumorigenesis.
AB  - Because oncogenic DNA viruses establish persistent infections in humans,
      continuous immunosurveillance for neoplastic cells is required to prevent virus
      induced tumors. Antigen-specific CD8+ T lymphocytes are critical in vivo
      effectors for eliminating virus-infected and virus-transformed cells.
      Investigation into the induction, regulation, and maintenance of CD8+ T cells
      specific for these viruses is hindered by the lack of tractable animal models
      that mimic natural infection. Resistance to tumors induced by polyoma virus, a
      persistent natural mouse DNA virus, is mediated by polyoma-specific CD8+ T cells.
      Mice susceptible to polyoma virus tumorigenesis mount a smaller, albeit still
      considerable, expansion of anti-polyoma CD8+ T cells; importantly, these
      antiviral CD8+ T cells lack cytotoxic activity while retaining the phenotype of
      cytotoxic T lymphocyte (CTL) effectors. In this review, we will discuss potential
      in vivo mechanisms that regulate the functional competence of anti-polyoma CD8+ T
      cells, particularly in the context of chronic antigenic stimulation provided by
      persistent viral infections and tumors.

PMID- 11572633
TI  - Vaccination against murine gamma-herpesvirus infection.
AB  - The gamma-herpesviruses establish life-long latency in the host and are important
      human pathogens. T cells play a major role in controlling the initial acute
      infection and subsequently maintaining the virus in a quiescent state. However,
      the nature of the T-cell response to gamma-herpesvirus infection and the
      requirements for effective vaccination are poorly understood. The recent
      development of a murine gamma-herpesvirus (murine herpesvirus-68 [MHV-68]) has
      made it possible to analyze T-cell responses and test vaccination strategies in a
      small animal model. Intranasal infection with MHV-68 induces an acute infection
      in the lung and the subsequent establishment of long-term latency, which is
      associated with splenomegaly and an infectious mononucleosis-like syndrome. Here
      we review the T-cell response to different phases of the infection and the impact
      of vaccination against either lytic-cycle, or latency-associated T-cell epitopes.

PMID- 11572634
TI  - Virus-induced autoimmunity: potential role of viruses in initiation,
      perpetuation, and progression of T-cell-mediated autoimmune disease.
AB  - Virus infections have been implicated in the initiation of multiple human
      autoimmune diseases. This article focuses on reviewing the role of viruses in
      initiation, progression, and perpetuation of autoimmune diseases. Various
      mechanisms by which virus infections can induce autoimmune responses including
      molecular mimicry, epitope spreading, direct bystander activation, and release of
      cryptic epitopes are discussed. Evidence implicating virus infections in the
      pathogenesis of various human autoimmune diseases is reviewed. Last, the
      characteristics of animal models that have been developed for the study of the
      potential role of viruses in the initiation and progression of autoimmune disease
      are reviewed.

PMID- 11572635
TI  - West nile virus surveillance in Romania: 1997-2000.
AB  - In response to the 1996 West Nile (WN) fever epidemic that occurred in Bucharest
      and southeastern Romania, a surveillance program was established. The
      surveillance system detected 39 clinical human WN fever cases during the period
      1997-2000: 14 cases in 1997, 5 cases in 1998, 7 cases in 1999, and 13 cases in
      2000. Thirty-eight of the 39 case-patients lived in the greater Danube Valley of
      southern Romania, and 1 case-patient resided in the district of Vaslui, located
      on the Moldavian plateau. The estimated annual case incidence rate for the
      surveillance area during the period 1997-2000 was 0.95 cases per million
      residents. Thirty-four cases were serologically confirmed, and 5 cases were
      classified as probable. Twenty-four case-patients presented with clinical
      symptoms of meningitis (62%), 12 with meningoencephalitis (31%), 1 with
      encephalitis (3%), and 2 with febrile exanthema (5%). Five of the 39 cases were
      fatal (13%). Fourteen case-patients resided in rural areas, and 25 in urban and
      suburban areas, including 7 case-patients who resided in Bucharest. The ages of
      case-patients ranged from 8 to 76 years with a median age of 45 years. Twenty
      four case-patients were males and 15 were females. Dates of onset of illness
      occurred from May 24 through September 25, with 82% of onset dates occurring in
      August and September. Limited entomological surveillance failed to detect WN
      virus. Retrospective sampling of domestic fowl in the vicinity of case-patient
      residences during the years 1997-2000 demonstrated seroprevalence rates of 7.8%
      29%. Limited wild bird surveillance demonstrated seroprevalence rates of 5%-8%.
      The surveillance data suggest that WN virus persists focally for several years in
      poorly understood transmission cycles after sporadic introductions or that WN
      virus is introduced into Romania at relatively high rates, and persists
      seasonally in small foci.

PMID- 11572636
TI  - Isolation of single-chain antibody fragments against Venezuelan equine
      encephalomyelitis virus from two different immune sources.
AB  - Venezuelan equine encephalomyelitis (VEE) virus is an important human and
      veterinary pathogen of Central and South America. The virus can cause widespread
      epidemics, affecting hundreds of thousands of horses, and thousands of humans.
      Detection of the virus early in infection and in mosquito populations may allow
      epidemics to be predicted such that suitable prophylaxis, such as vaccination,
      can be used to reduce disease severity and transmission. The sensitivity and
      specificity of current immunoassays, based on conventional monoclonal and
      polyclonal antibodies, needs to be improved for the diagnosis of infection. We
      have examined phage display libraries expressing single-chain antibodies (scFv)
      produced from two different immune sources, a hybridoma cell line and an
      immunized mouse spleen. The libraries were panned against VEE virus to select for
      specific scFvs. scFvs isolated from both libraries were specific for the same
      epitope on the VEE virus and sequence analysis showed that the scFvs were almost
      identical apart from the CDR3 region of the heavy chain. The data presented in
      this article suggest that although scFvs may be useful tools for the detection of
      viruses, there are serious limitations with the use of phage display as a tool
      for the isolation of specific antibodies.

PMID- 11572637
TI  - Relations between tooth enamel dose and organ doses for electron spin resonance
      dosimetry against external photon exposure.
AB  - An analysis of doses to tooth enamel and to organs was carried out to develop a
      method that can predict the organ doses and the effective dose by electron spin
      resonance (ESR) dosimetry using tooth samples for external photon exposure.
      Absorbed dose to tooth enamel and organ doses were obtained by Monte Carlo
      calculations using the EGS4 code in combination with a mathematical human model
      with a newly defined teeth part. The calculations gave quantitative relations
      between tooth enamel dose and organ doses for some cases of external photon
      exposure. It was also found that tooth enamel dose depends more significantly on
      energy of incident photons than the other organ dose or the effective dose. The
      obtained data are to be useful for the assessment of individual dose in past
      exposure events by the ESR dosimetry using tooth enamel.

PMID- 11572638
TI  - Bladder wall dosimetry for 131I administered activities.
AB  - Detailed dosimetric calculations of bladder dose from 131I accumulations are
      presented, using Monte Carlo simulations and the dynamic bladder model proposed
      in the recent revision of MIRD Pamphlet No 14. Penetrating radiation and electron
      dose to the bladder wall inner surface, as well as within the bladder wall, per
      unit of 131I activity accumulated in the bladder, are calculated for various
      bladder filling volumes. The effect of backscatter was taken into account for
      photon dose calculations while electron dose was determined for all the beta
      spectral components of 131I. Dosimetric results were used to derive simple
      parameterisation functions of photon and electron dose with respect to bladder
      filling volume in combination with any bladder physiology model. Calculations of
      bladder dose per unit of 131I-OIH and 131I-NaI administered activity, using the
      derived parametrisations, differ by less than 12% from corresponding results
      given in the recent revision of MIRD Pamphlet No 14.

PMID- 11572639
TI  - Study of the correlation between administered activity and radiation committed
      dose to the thyroid in 131I therapy of Graves' disease.
AB  - Substantial reduction in the thyroid volume (up to 70-80%) after 131I therapy of
      Graves' disease has been demonstrated and reported in the literature. Recently a
      mathematical model of thyroid mass reduction during the first month after therapy
      has been developed and a new algorithm for the radiation committed dose
      calculation has been proposed. Reduction of the thyroid mass and the radiation
      committed dose to the gland depend on a parameter k, defined for each subject.
      The calculation of k allows the prediction of the activity to administer,
      depending on the radiation committed dose chosen by the physician. In this paper
      a method for calculating k is proposed. The calculated values of k are compared
      to values derived from measurements of the changes in thyroid mass in twenty-six
      patients treated by 131I for Graves' disease. The radiation committed dose to the
      thyroid can be predicted within 21%, and the radioiodine activity to administer
      to the patient can be predicted within 22% using the calculated values of k. The
      thyroid volume reduction during the first month after therapy administration can
      be also predicted with good accuracy using the calculated values of k. The
      radiation committed dose and the radioiodine activity to administer were
      calculated using a new, very simple algorithm. A comparison between the values
      calculated by this new algorithm and the old, classical Marinelli-Quimby
      algorithm shows that the new method is more accurate.

PMID- 11572640
TI  - Experimental simulation of A-bomb gamma ray spectra for radiobiology studies.
AB  - Improved radiation protection of humans requires a better understanding of the
      mechanisms of radiation action and accurate estimates of radiation risk for both
      internal and external radiations. The Japanese atomic bomb survivors represent
      one of the most important sources of human data on the late carcinogenic effects
      of ionising radiations. The present study was undertaken to investigate whether
      it would be possible to use hospital radiotherapy/radiobiology equipment to mimic
      the spectra encountered in Hiroshima and Nagasaki. The estimated total gamma ray
      fluence spectra (including both prompt and delayed photons) at both Hiroshima and
      Nagasaki, for distances of 500, 1000, 1500 and 2000 m have been evaluated using
      DS86 data and previously unpublished information for delayed gamma radiations
      which constitute the major contribution to survivor doses. Monte Carlo (EGS4)
      simulations were performed to transport these photons through the body in order
      to investigate the variation in electron spectra for various body organs. The
      electron spectra obtained for these fluences at, for example, the colon, have
      been matched with combinations of electron spectra produced by linear
      accelerators to within 5% SD. These will, for the first time, enable a direct
      link to be made between radiobiological studies (for example, on mammography
      spectra) and the epidemiological data from Japan, which currently underpin
      radiation risk estimates.

PMID- 11572641
TI  - The application of non-parametric statistical techniques to an ALARA programme.
AB  - For the cost-effective reduction of occupational radiation dose (ORD) at nuclear
      power plants, it is necessary to identify what are the processes of repetitive
      high ORD during maintenance and repair operations. To identify the processes, the
      point values such as mean and median are generally used, but they sometimes lead
      to misjudgment since they cannot show other important characteristics such as
      dose distributions and frequencies of radiation jobs. As an alternative, the non
      parametric analysis method is proposed, which effectively identifies the
      processes of repetitive high ORD. As a case study, the method is applied to ORD
      data of maintenance and repair processes at Kori Units 3 and 4 that are
      pressurised water reactors with 950 MWe capacity and have been operating since
      1986 and 1987 respectively, in Korea and the method is demonstrated to be an
      efficient way of analysing the data.

PMID- 11572642
TI  - Analysis of radiation workers' dose records in the Korean National Dose Registry.
AB  - Data are presented on the externally received personal dose equivalent for
      radiation workers who used the Korea Radioisotope Association's personal
      monitoring and dose record keeping service since 1984, and provide initial
      statistics on Korean workers who have been exposed to ionising radiation in
      different occupations. The total number of workers registered during the period
      of 1984 to 1999 was 64,518. The number increased steadily and the accumulated
      dose also increased. The proportion of radiation workers by occupation was 38.4%
      for nuclear power plants, 20.3% for industrial organisations and 12.4% for non
      destructive industry. The annual collective dose of radiation workers was 31.72
      man.Sv in 1999. The mean annual dose by sex was 1.49 mSv for males and 0.56 mSv
      for females and the mean annual dose for a worker was 1.41 mSv with the highest
      mean dose being received by non-destructive industry (3.53 mSv). Very few workers
      (0.8%) received more than 20 mSv (2 rem) and only one more than 50 mSv, the legal
      limit for an annual dose increase. There has been a steady decline in the mean
      dose since 1984, showing a significant decrease in dose with time (p<0.001). The
      data showed that radiation protection in Korea was improving, though annual doses
      were still higher than other countries.

PMID- 11572643
TI  - Effective doses and organ doses in the MIRD-5 phantom exposed to monoenergetic
      0.1 MeV to 200 MeV electrons in the LAT direction.
AB  - Organ doses and effective doses were calculated using the EGS-4 Monte Carlo
      simulation code and a MIRD-5 mathematical human phantom placed in a vacuum. For
      broad right and left lateral beams of monoenergetic (0.1-200 MeV) electrons,
      conversion coefficients from the incident fluence to organ dose, to effective
      dose, and to effective dose equivalent were obtained. There were no clear
      differences between the conversion coefficients in the case of left-lateral
      (LLAT) and right-lateral (RLAT) irradiation. Therefore, when investigating
      lateral geometries for electron exposure, it is not necessary to evaluate both
      directions independently. In general, conversion coefficients for lateral
      irradiation (LAT) were smaller than those for AP and PA. The difference between
      the AP and PA conversion coefficients and LAT became smaller with increasing
      incident energy; at 200 MeV the conversion coefficients were almost independent
      of the irradiation geometry. The agreement between the results of the present
      study and those of other studies was acceptable within the statistical
      uncertainties.

PMID- 11572644
TI  - Indoor radon concentrations in Poland as determined in short-term (two-day)
      measurements.
AB  - The aim of the present work was to obtain a pattern of 222Rn concentration
      distributions in typical buildings in Poland. In the investigations, the
      environmental passive detectors of the PICO-RAD type were used. The study
      encompassed buildings that were typical for Poland. The distribution of airborne
      222Rn concentrations indoors is of a log-normal type. A total 1171 detectors were
      measured. Measurements were made in 319 basements, the remaining 852 measurements
      were carried out in the inhabited part of the houses. The radon concentrations in
      the basements in Bq x m(-3) ranged from 6 to 1300 with the arithmetic mean AM =
      60, geometric mean GM = 30 and median M = 28, whereas those in the inhabited
      parts of the house (above the ground level) were: AM = 25, GM = 17 and M = 16
      with the highest record value of 420.

PMID- 11572645
TI  - Remains of 137Cs contamination in the city of Goiania, Brazil.
AB  - The results of measurements, performed in 1999, of the remaining 137Cs
      contamination in some of the sites where fragments of a radioactive source of a
      teletherapy unit had been manipulated in 1987 are presented. This episode
      occurred in the city of Goiania, during Brazil's worst radiological accident ever
      reported. Using the technique of gamma ray spectrometry, analyses of both surface
      and profile soil and vegetable samples were made. High values of 137Cs activity
      per unit mass were found in soil layers at depths between 10 and 40cm from the
      surface. Some values exceeded by up to eight times the action level of 22.5 kBq x
      kg(-1) proposed by the Brazilian National Nuclear Energy Commission (CNEN) during
      the decontamination process at the time of the accident, for the first year after
      the accident. Absorbed dose rates at 1 m above the ground were calculated from
      the data of 137Cs concentration in the soil and compared with those obtained from
      in situ gamma ray spectrometry and from thermoluminescence dosimetry.

PMID- 11572646
TI  - Personal dose monitoring of employees at the institute of modern physics, China.
AB  - The radiation field at the accelerator facility consists of radiation produced
      immediately and of secondary radiation induced by activation etc. As the
      accelerator building and the experimental hall are closed and inaccessible during
      accelerator operation, the exposure received by the employees at the IMP
      (Institute of Modern Physics) comes almost totally from the induced radiation.
      The methods and the results of personal dose monitoring from 1986 to 1999 at the
      IMP are presented. During the period, the total number of monitored individuals
      was 1960, and the average annual effective dose was 0.10 mSv. The number
      recording less than 0.1 mSv of effective dose was 1471 individuals. amounting to
      77% of the total. Only six individuals had received effective doses between 5.0
      mSv and 10 mSv. The maximum effective dose of 10 mSv was received by workers
      repairing the accelerator.

PMID- 11572647
TI  - The relationship between localised SAR in the arm and wrist current.
AB  - Calculations are presented of the specific energy absorption rate, SAR, in the
      lower arm of the NRPB anatomically realistic voxel model. NORMAN, for induced
      currents from 100 kHz to 80 MHz. The wrist region has a narrow cross section and
      contains little high conductivity muscle, comprising mainly low conductivity
      bone, tendon and fat. Consequently there is a channelling of the current through
      the high conductivity muscle, which produces high, localised values of the SAR.
      Values averaged over 10 g and 100 g of tissue are calculated as a function of the
      current flowing through the wrist.

PMID- 11572648
TI  - A note on the charging of aerosols by overhead line corona.
AB  - Elevated concentrations of corona ions have been measured in the vicinity of high
      voltage overhead lines. It is shown that the integrated ion exposure of aerosols
      in the corona plume is of the order of (x/u)n(x) where n(x) is the ion
      concentration at distance x downwind from the line and u is the wind speed.
      Estimated ion exposures are of order 10(11) m(-3) x s, less then 1% of the 10(13)
      m(-3) x s needed to cause saturation charging of 20 nm aerosols. It is suggested
      that it is not valid to postulate that AC corona is a health hazard as a
      consequence of its charging aerosols in the size range 20-125 nm.

PMID- 11572649
TI  - The power of the spoken word.

PMID- 11572650
TI  - Perspectives on genomics and antibiotic discovery.

PMID- 11572651
TI  - Antibacterial agents (oxazolidinones, quinolones, macrolides and new agents):
      patent highlights June to December 2000.
AB  - Several patent disclosures were made on oxazolidinone, quinolone, macrolide and
      new antimicrobial agents between June and December 2000; 26 of these patents are
      discussed in this review. The exciting report on new oxazolidinone derivatives
      with potent activity against fastidious Gram-negative organisms is highlighted.
      Most of the new quinolones are structurally dissimilar to the traditional
      fluoroquinolones and demonstrate activity against Helicobacter pylori (MIC=0.013
      microg/ml). New 14-membered macrolides with broad-spectrum activity including
      against Mycobacterium avium are also presented. A novel peptidic antibiotic with
      potent antimicrobial activity against Streptococcus pneumoniae (MIC<0.0005
      microg/ml) is also highlighted.

PMID- 11572652
TI  - RU-79115 (Aventis Pharma).
AB  - Aventis Pharma AG is investigating a series of novel coumarin DNA gyrase B
      inhibitors, including RU-79115, as potential treatments for bacterial infections.
      These inhibitors have displayed potent inhibitory activity in vitro against DNA
      supercoiling by DNA gyrase B and have antibacterial activity. Good antibacterial
      activity against vancomycin- and teicoplanin-resistant enterococci was observed
      with most analogs (where the 3-acylamino residue was replaced with reversed
      isosteres). Amide derivatives were also active against novobiocin-resistant
      strains [335149]. RU-79115 has shown activity against Gram-positive bacteria,
      particularly staphylococci and enterococci, and its activity compares favorably
      to vancomycin. Against oxacillin- and ofloxacin-resistant staphylococci, RU-79115
      had MIC50 values 7.5-fold lower than eperezolid and significantly lower than
      vancomycin. In vivo data suggest that the compound is safe and carries a
      satisfactory pharmacokinetic profile [216256], [340969], [376199]. The compound
      is the most potent in the series which also includes RU-78535 and RU-64135
      [340969], [341039].

PMID- 11572653
TI  - Tobramycin (Cystic Fibrosis Foundation/PathoGenesis).
AB  - TOBI, the inhalant formulation of the antibiotic tobramycin, is a clear, sterile,
      preservative-free, aqueous solution with the pH and salinity adjusted
      specifically for administration by a compressed-air driven nebulizer. It was
      launched in the US in January 1998 for use in cystic fibrosis (CF) patients with
      chronic pulmonary Pseudomonas aeruginosa infections [315294]. In March 1998,
      PathoGenesis filed for approval in Canada for this indication, and the Health
      Protection Branch granted TOBI a Priority Review [281940]. The compound was
      approved in both Canada and Argentina in February 1999 1312484], and launched in
      these countries in May 1999 [324276], [326053]. It was approved in Israel in
      January 2000 [351769] and in Australia in February 2000 [356941] and launched in
      the two countries in August 2000 [396142]. In March 2000, PathoGenesis and
      AeroGen Inc agreed to collaborate on developing the use of AeroGen's AeroDose
      inhaler for the delivery of tobramycin. The aim is to reduce the delivery time
      from 15 to 20 min to 5 to 10 min. Phase I trials with the inhaler were planned
      for the second quarter of 2000 [358125] and the product is expected to be in
      phase III trials by 2002 [396509]. TOBI is also under investigation for the
      treatment of non-CF patients with lung infection. In June 2000, PathoGenesis
      initiated a phase II trial of TOBI in bronchiectasis patients with Pseudomonas
      lung infections to assess whether TOBI improves symptoms associated with severe
      bronchiectasis [372767].

PMID- 11572654
TI  - ABT-773 (Abbott Laboratories).
AB  - ABT-773 is a macrolide antibacterial agent under development by Abbott
      Laboratories and Taisho Pharmaceutical Co Ltd for the potential treatment of
      bacterial infection [266579]. As of February 2001, ABT-773 had entered phase III
      trials in the US [398274]. Japanese phase II trials were expected to commence in
      June 2000 and a phase II trial is being designed for respiratory infections, with
      Abbott expecting filing in March 2002 [360455]. The bioavailability of ABT-773 in
      humans is unaffected by food [383228] and in a phase I, randomized, double-blind
      trial in healthy males only mild adverse effects, usually affecting the
      gastrointestinal system, were observed [383208]. Under an agreement, Abbott and
      Taisho are conducting joint research to discover new compounds; Abbott will have
      worldwide marketing, manufacturing and supply rights (except in Japan), and
      Taisho will receive royalties on Abbott's sales in consideration of granted
      rights. In Japan, the companies will co-market any resulting compounds [266579].
      ABT-773 demonstrated good activity in vitro and in vivo against Streptococcus
      pneumoniae and Staphylococcus aureus [383229], [383231], and was highly potent
      even against macrolide-resistant [382149], [382150] and invasive [383782] S
      pneumoniae.

PMID- 11572655
TI  - The CD40-CD40 ligand system: a potential therapeutic target in atherosclerosis.
AB  - Atherosclerosis is a leading cause of cardiovascular disease in the westernized
      world. This review highlights emerging evidence linking atherosclerosis to the
      CD40-CD40 ligand (CD154) pathway. Recently, atherosclerosis has been associated
      with chronic inflammation, linking it to the immune system. This novel viewpoint
      may serve as an additional target for therapeutic intervention. CD40 and CD154
      are highly expressed in atherosclerotic human plaques. Recent data from
      preclinical animal models of atherosclerosis show that disruption of the CD40
      CD154 pathway can prevent atherosclerotic progression and may reverse established
      lesions. Blockade of the CD40-CD154 pathway by biologicals or small molecules may
      prove valuable in the treatment of atherosclerosis.

PMID- 11572656
TI  - Macrophage migration inhibitory factor as a target molecule in multiple
      sclerosis.
AB  - Various therapeutic approaches to multiple sclerosis (MS) have been presented,
      but no specific and effective method has so far been established. In recent
      years, macrophage migration inhibitory factor (MIF) has been re-evaluated as a
      pluripotent cytokine involved in a broad spectrum of inflammation and immune
      responses. During the course of MIF study, increased levels of MIF were observed
      in the cerebrospinal fluids of patients with MS in parallel with exacerbation of
      clinical symptoms, and a number of lymphocytes strongly expressing MIF infiltrate
      into the pathogenic lesions. It is expected that regulation of the action of MIF
      by an anti-MIF antibody or small molecule inhibitors would be an effective
      therapeutic method for this demyelinating disease.

PMID- 11572657
TI  - New developments in the treatment of ischemia/reperfusion injury.
AB  - Currently, the treatment of reperfusion following ischemia is primarily
      supportive. Preventative measures may help in combating the occurrence of
      ischemia, but minimizing the secondary damage that occurs with the onset of
      reperfusion would improve outcomes. In this review, using a Medline search, we
      have outlined the current knowledge with respect to the pathophysiology of this
      disease process and focused primarily on the basic science investigations of
      drugs, including natural therapies, which have shown potential. It is becoming
      increasingly clear that no one method or drug is the magic elixir that solely
      treats reperfusion injury due to the complex and interconnected processes
      involved.

PMID- 11572658
TI  - AdGVVEGF121.10 (GenVec).
AB  - GenVec, in collaboration with Pfizer (formerly Parke-Davis), is developing
      AdGVVEGF121.10 (BioBypass), a gene therapy involving the 121-residue isoform of
      vascular endothelial growth factor (VEGF), licensed from Scios, for the potential
      treatment of coronary artery disease (CAD) and peripheral vascular disease (PVD)
      [262000]. By March 2000, phase II trials in CAD had commenced [359531], [359532],
      [359538]. By August 2000, phase II trials were also underway for PVD [386293].
      The initial phase II trial will include approximately 70 patients with severe CAD
      who are not candidates for bypass surgery and will assess exercise capacity and
      patient well-being, before and after treatment, as well as safety and drug
      tolerance [364137]. Scios licensed the gene transfer applications of VEGF121 to
      GenVec in June 1996 [263381]. In September 1997, GenVec entered into an agreement
      with Parke-Davis, a subsidiary of Warner-Lambert (now Pfizer), to develop the
      therapy [262000]. In May 1999, Warner-Lambert signed an agreement with Bioscience
      for a device for the administration of AdGVVEGF121.10 1325443]. In May 2000,
      Merrill Lynch predicted a US filing in the first half of 2003 [375962]. In
      January 2001, AG Edwards predicted the product would generate $70 million in
      revenues to Pfizer and $12 million in royalties to GenVec in 2005. In February
      1999, GenVec was awarded US-05846782, covering vectors for targeting the transfer
      of therapeutic genes to specific tissues in the human body [316038].

PMID- 11572659
TI  - VEGF-2 (St Elizabeth's Medical Center).
AB  - St Elizabeth's Medical Center of Boston is developing VEGF gene therapy for the
      potential treatment of angina and diabetic neuropathy. The center is studying
      three isoforms of VEGF, although the expression of phVEGF165 has yielded the most
      positive results [312563]. VEGF-2 gene therapy augments perfusion of ischemic
      myocardium that contributes to improved clinical outcomes in patients with
      chronic myocardial ischemia as assessed by NOGA electromechanical mapping
      [390786]. Phase I trials demonstrated that gene transfer directly into the heart
      of the patient facilitates blood flow to the primary muscles of the heart,
      providing relief of angina [348564]. Reduced angina was reported by 28 out of 30
      patients and tolerance of exercise increased from 240 to 410 s up to 180 days
      post-therapy [348632].

PMID- 11572660
TI  - Acute spinal cord injury: pharmacotherapy and drug development perspectives.
AB  - There are no drugs specifically approved for spinal cord injury that directly
      address the underlying damage to neural tissue. Immediate treatment with
      methylprednisolone sodium succinate has been shown to improve outcome from injury
      in a series of preclinical and clinical studies, and it is now widely used,
      though the benefits appear to be modest. A variety of other approaches to
      protecting the injured spinal cord from secondary pathological processes have
      been examined experimentally, including antioxidants, membrane stabilizers,
      glutamate antagonists, anti-inflammatories, caspase inhibitors, calpain
      inhibitors and other compounds of uncertain mechanism. All of these approaches
      have been supported by positive animal studies but their efficacy relative to the
      widely used methylprednisolone has not been established.

PMID- 11572661
TI  - Safinamide (Newron Pharmaceuticals).
AB  - Safinamide (formerly PNU-151774E), a sodium and calcium channel modulator that
      also inhibits monoamine oxidase B (MAOB), is under development by Newron
      Pharmaceuticals for the potential treatment of epilepsy, Parkinson's disease
      (PD), pain and stroke [345222], [348351]. Phase I trials for epilepsy and PD have
      been completed, and dose-finding studies for both indications had commenced in
      March 2001 [401685]. The compound was previously developed by Pharmacia & Upjohn
      (P&U) for the potential treatment of epilepsy, an indication for which it
      initially reached phase I trials [294891], [345007]. Newron acquired the rights
      to safinamide from P&U at the end of 1998. Results from two phase I trials of the
      compound (single ascending dose and steady state at three doses), completed in
      March 2000, demonstrated that the drug is well tolerated with good
      bioavailability and linear pharmacokinetics [359652].

PMID- 11572662
TI  - Gacyclidine (Beaufour-Ipsen).
AB  - Beaufour-Ipsen is developing gacyclidine (GK-11) for the potential treatment of
      traumatic brain injury. Phase II clinical trials of the compound for this
      indication had been completed as of October 1999 and the company is looking for a
      partnership before undertaking further clinical development for this and,
      possibly, other indications [344879], [346265], [386763]. Phase II trials for
      acute spinal cord injury gave disappointing results and development for this
      indication has been discontinued [344879].

PMID- 11572663
TI  - BMS-204352 (Bristol Myers Squibb).
AB  - BMS-204352 is a fluoro-oxindole potassium channel opener being developed by
      Bristol-Myers Squibb as a potential neuroprotectant for the treatment of acute
      ischemic stroke. Phase I trials were underway in Japan in 1998 [288541]. By July
      1999, it was in phase II trials in the US [331682] and by October 2000, phase II
      trials had also begun in Japan [384751]. At the 219th American Chemical Society
      meeting in March 2000, it was reported that BMS-204352 had entered worldwide
      phase III trials involving patients with suspected acute stroke [362077],
      [361291]. In February 2001, Credit Suisse First Boston predicted sales of $111
      million in 2005 [399484]. In February 1999, Lehman Brothers predicted the drug
      had a 30% probability of reaching market, with an estimated first launch date in
      2004. The analysts predicted peak sales would occur in 2008, with sales of $500
      million in the US at that time [319225].

PMID- 11572664
TI  - Soretolide (Laboratoires Biocodex).
AB  - Laboratoires Biocodex is developing soretolide (D-2916) as a potential treatment
      for epilepsy. It is currently in phase II trials [299344]. In animal models,
      soretolide shows an anticonvulsant profile similar to carbamazepine, being active
      in the maximal electroshock test and poorly active against pentylenetetrazole
      induced seizures [299344]. The company is currently discussing future development
      plans for this drug [410625].

PMID- 11572665
TI  - Pregabalin (Pfizer).
AB  - Pfizer is developing pregabalin, a follow-up compound to its GABA agonist
      gabapentin, for the potential treatment of several central nervous system (CNS)
      disorders including epilepsy, neuropathic pain, anxiety and social phobia
      [286425]. By December 2000, Pfizer anticipated filing an NDA for pregabalin for
      seven major indications (beginning with neuropathic pain and add-on epilepsy),
      with the FDA by the end of 2001. Filings for generalized anxiety disorder (GAD),
      social anxiety disorder and fibromyalgia are expected to take place in 2002, and
      filings for epilepsy monotherapy and panic disorders are expected to take place
      in early- and late-2003, respectively [336918], [393182], [399956]. By January
      2001, pregabalin was in phase II development in Japan for the potential treatment
      of neuropathic pain, with an anticipated approval date of 2005 [394827]. However,
      following analysis by the FDA of a mouse study that showed incidence of a
      specific tumor type, Pfizer announced in February 2001, that it is restricting
      the use of pregablin in some clinical patients [398726] and it has frozen trials
      for neuropathic pain [398785]. In April 2001, Morgan Stanley Dean Witter
      predicted potential sales of $350 million in 2002, rising to $1750 million in
      2006, with peak sales in excess of $2000 million [406923].

PMID- 11572666
TI  - Gene-directed enzyme prodrug therapy (GDEPT)--recognizing the present limitations
      of gene therapy for the treatment of cancer.

PMID- 11572667
TI  - Use of hypoxia-regulated gene expression in tumor-specific gene therapy.
AB  - The presence of hypoxic cells in human solid tumors is an important factor
      leading to resistance to radiation therapy and chemotherapy. However, differences
      in the oxygen tension between normal tissues and tumors also provide the
      potential for designing tumor-specific gene therapy. The strategy is to
      selectively induce the expression of suicide genes under hypoxia and thereby
      preferentially kill hypoxic cells. The hypoxia-responsive vector regulates gene
      expression via the hypoxia-responsive element, which can be activated through the
      transcriptional complex hypoxia-inducible factor 1. A gene therapy that is based
      on hypoxia-regulated gene expression needs to consider the suicide gene, the
      genetic vector, the delivery method and the bystander effect. These factors pose
      considerable challenges for the development of a successful hypoxia-directed gene
      therapy, but once this has been achieved, this type of therapy in combination
      with traditional radiation and chemotherapy should provide an improved clinical
      outcome for patients with these diseases.

PMID- 11572668
TI  - GVAX (Cell Genesys).
AB  - Cell Genesys (formerly Somatix Therapy Corp) is developing GVAX as a potential
      cancer vaccine for various tumor types. Clinical trials have commenced for
      melanoma, renal tumor, lung tumor, pancreatic tumor, prostate tumor and multiple
      myeloma [191143], [287470], [298308], [367408], [401114]; trials are planned for
      2001 in leukemia (phase I) and pancreatic cancer (phase II) [366918], [388814]. A
      worldwide collaboration was signed with Japan Tobacco in December 1998, covering
      the application of GVAX in prostate cancer trials [312213]. This collaboration
      may be extended to lung cancer and melanoma, depending on the clinical trial
      results for prostate cancer [309873], [311835]. The Japanese clinical trials were
      put on hold on 21 September 2000 due to problems with the mass production of
      cells by Cell Genesys [384885]. Somatix was developing GVAX until its merger with
      Cell Genesys in June 1997 [248422]. In April 2001, Cell Genesys initiated the
      first in a series of trials of a high-potency version of GVAX prostate cancer
      vaccine following encouraging phase II data reported for its first-generation
      product. The high-potency form of GVAX is similar to the first-generation product
      except that it releases an increased quantity of immune system stimulant
      [405932].

PMID- 11572669
TI  - Highly stereoselective synthesis of homoallylic amines based on addition of
      allyltrichlorosilanes to benzoylhydrazones.
AB  - Allyltrichlorosilanes reacted with benzoylhydrazones in DMF without the use of
      any catalyst to afford the corresponding homoallylic benzoylhydrazines in good to
      high yields. The reactions proceeded at 0 degrees C to room temperature under
      mild conditions. In addition, it was found that the reactions tolerated well the
      steric hindrance of hydrazones and allyltrichlorosilanes. Indeed, ketone-derived
      benzoylhydrazones reacted with allyltrichlorosilane smoothly to afford the
      corresponding N'-tert-alkyl-N-benzoylhydrazines in high yields. In crotylation
      with (E)- and (Z)-crotyltrichlorosilanes, syn- and anti-adducts were
      stereospecifically obtained, respectively. These reactions are most likely to
      proceed via a cyclic chairlike transition state where the R group takes an axial
      position. When alpha-heteroatom-substituted chiral benzoylhydrazones were used,
      high anti-diastereoselectivities were observed. These adducts can be readily
      converted to homoallylic amines in high yields without epimerization.

PMID- 11572670
TI  - Reference scales for the characterization of cationic electrophiles and neutral
      nucleophiles.
AB  - Twenty-three diarylcarbenium ions and 38 pi-systems (arenes, alkenes, allyl
      silanes and stannanes, silyl enol ethers, silyl ketene acetals, and enamines)
      have been defined as basis sets for establishing general reactivity scales for
      electrophiles and nucleophiles. The rate constants of 209 combinations of these
      benzhydrylium ions and pi-nucleophiles, 85 of which are first presented in this
      article, have been subjected to a correlation analysis to determine the
      electrophilicity parameters E and the nucleophilicity parameters N and s as
      defined by the equation log k(20 degrees C) = s(N + E) (Mayr, H.; Patz, M. Angew.
      Chem., Int. Ed. Engl. 1994, 33, 938-957). Though the reactivity scales thus
      obtained cover more than 16 orders of magnitude, the individual rate constants
      are reproduced with a standard deviation of a factor of 1.19 (Table 1). It is
      shown that the reactivity parameters thus derived from the reactions of
      diarylcarbenium ions with pi-nucleophiles (Figure 3) are also suitable for
      characterizing the nucleophilic reactivities of alkynes, metal-pi-complexes, and
      hydride donors (Table 2) and for characterizing the electrophilic reactivities of
      heterosubstituted and metal-coordinated carbenium ions (Table 3). The reactivity
      parameters in Figure 3 are, therefore, recommended for the characterization of
      any new electrophiles and nucleophiles in the reactivity range covered. The
      linear correlation between the electrophilicity parameters E of benzhydryl
      cations and the corresponding substituent constants sigma(+) provides Hammett
      sigma(+) constants for 10 substituents from -1.19 to -2.11, i.e., in a range with
      only very few previous entries.

PMID- 11572671
TI  - Radical polymerization of styrene controlled by half-sandwich Mo(III)/Mo(IV)
      couples: all basic mechanisms are possible.
AB  - Density functional calculations of bond dissociation energies (BDEs) have been
      used as a guide to the choice of metal system suitable for controlling styrene
      polymerization by either the stable free radical polymerization (SFRP) or the
      atom transfer radical polymerization (ATRP) mechanism. In accord with the
      theoretical prediction, CpMo(eta(4)-C(4)H(6))(CH(2)SiMe(3))(2), 2, is not capable
      of yielding SFRP of styrene. Still in accord with theoretical prediction,
      CpMo(eta(4)-C(4)H(6))Cl(2), 1, CpMo(PMe(3))(2)Cl(2), 3, and CpMo(dppe)Cl(2) (dppe
      = 1,2-bis(diphenylphosphino)ethane), 4, yield controlled styrene polymerization
      by the SFRP mechanism in the presence of 2,2'-azobisisobutyronitrile (AIBN). This
      arises from the generation of a putative Mo(IV) alkyl species from the AIBN
      generated radical addition to the Mo(III) compound. The controlled nature of the
      polymerizations is indicated by linear M(n) progression with the conversion in
      all cases and moderate polydispersity indices (PDIs). Controlled polymerization
      of styrene is also given by compounds 3 and 4 in combination with alkyl bromides.
      These complexes then operate by the ATRP mechanism, again in accord with the
      theoretical predictions. Controlled character is revealed by linear increase of
      M(n) versus conversion, low PDIs, a stop-and-go experiment, and (1)H NMR and
      MALDI-TOF analyses of the polymer end groups. The same controlled polymerization
      is given by a "reverse" ATRP experiment, starting from AIBN and
      CpMo(PMe(3))(2)Cl(2)Br, 5. On the other hand, when compound 1 or 2 is used in
      combination with an alkyl bromide (as for an ATRP experiment), the isolated
      polystyrene shows by M(n), (1)H NMR, and MALDI-TOF analyses that catalytic chain
      transfer (CCT) radical polymerization takes place in this case. Kinetics
      simulations underscore the conditions regulating the radical polymerization
      mechanism and the living character of the polymerization. The complexes herein
      described are ineffective at controlling the polymerization of methyl
      methacrylate.

PMID- 11572672
TI  - Iridium complex-catalyzed allylic amination of allylic esters.
AB  - Iridium complex-catalyzed allylic amination of allylic carbonates was studied.
      The solvent strongly affected the catalytic activity. The use of a polar solvent
      such as EtOH is essential for obtaining the products in high yield. The reaction
      of (E)-3-substituted-2-propenyl carbonate and 1-substituted-2-propenyl carbonate
      with pyrrolidine in the presence of a catalytic amount of [Ir(COD)Cl](2) and
      P(OPh)(3) (P/Ir = 2) gave a branch amine with up to 99% selectivity. Both
      secondary and primary amines could be used for this reaction. When a primary
      amine was used, selective monoallylation occurred. No diallylation product was
      obtained. The reaction of 1,1-disubstituted-2-propenyl acetate with amines
      exclusively gave an alpha,alpha-disubstituted allylic amine. This reaction
      provides an alternative route to the addition of an organometallic reagent to
      ketimines for the preparation of such amines. The reaction of (Z)-3-substituted-2
      propenyl carbonate with amines gave (Z)-linear amines with up to 100%
      selectivity. In all cases, no (E)-linear amine was obtained. The selectivities
      described here have not been achieved in similar palladium complex-catalyzed
      reactions.

PMID- 11572673
TI  - A practical synthesis of (+)-discodermolide and analogues: fragment union by
      complex aldol reactions.
AB  - A practical stereocontrolled synthesis of (+)-discodermolide (1) has been
      completed in 10.3% overall yield (23 steps longest linear sequence). The absolute
      stereochemistry of the C(1)-C(6) (7), C(9)-C(16) (8), and C(17)-C(24) (9)
      subunits was established via substrate-controlled, boron-mediated, aldol
      reactions of the chiral ethyl ketones 10, 11, and 12. Key fragment coupling
      reactions were a lithium-mediated, anti-selective, aldol reaction of aryl ester 8
      (under Felkin-Anh induction from the aldehyde component 9), followed by in situ
      reduction to produce the 1,3-diol 40, and a (+)-diisopinocampheylboron chloride
      mediated aldol reaction of methyl ketone 7 (overturning the inherent substrate
      induction from the aldehyde component 52) to give the (7S)-adduct 58. The
      flexibility of our overall strategy is illustrated by the synthesis of a number
      of diastereomers and structural analogues of discodermolide, which should serve
      as valuable probes for structure-activity studies.

PMID- 11572674
TI  - Oligosaccharide synthesis with glycosyl phosphate and dithiophosphate triesters
      as glycosylating agents.
AB  - Described is an efficient one-pot synthesis of alpha- and beta-glycosyl phosphate
      and dithiophosphate triesters from glycals via 1,2-anhydrosugars. Glycosyl
      phosphates function as versatile glycosylating agents for the synthesis of beta
      glucosidic, beta-galactosidic, alpha-fucosidic, alpha-mannosidic, beta-glucuronic
      acid, and beta-glucosamine linkages upon activation with trimethylsilyl
      trifluoromethanesulfonate (TMSOTf). In addition to serving as efficient donors
      for O-glycosylations, glycosyl phosphates are effective in the preparation of S
      glycosides and C-glycosides. Furthermore, the acid-catalyzed coupling of glycosyl
      phosphates with silylated acceptors is also discussed. Glycosyl dithiophosphates
      are synthesized and are also used as glycosyl donors. This alternate method
      offers compatibility with acceptors containing glycals to form beta-glycosides.
      To minimize protecting group manipulations, orthogonal and regioselective
      glycosylation strategies with glycosyl phosphates are reported. An orthogonal
      glycosylation method involving the activation of a glycosyl phosphate donor in
      the presence of a thioglycoside acceptor is described, as is an acceptor-mediated
      regioselective glycosylation strategy. Additionally, a unique glycosylation
      strategy exploiting the difference in reactivity of alpha- and beta-glycosyl
      phosphates is disclosed. The procedures outlined here provide the basis for the
      assembly of complex oligosaccharides in solution and by automated solid-phase
      synthesis with glycosyl phosphate building blocks exclusively or in concert with
      other donors.

PMID- 11572675
TI  - Alternating stereospecific copolymerization of ethylene and propylene with
      metallocene catalysts.
AB  - The copolymerization of ethylene and propylene with bridged metallocenes Me(2)E(3
      RCp)(Flu)X(2)/MAO (E = C, X = Me; E = Si, X = Cl; R = H or alkyl) was
      investigated. Ethylene/propylene copolymerization with metallocenes having
      heterotopic active sites (R =Me, i-Pr) yield alternating, isotactic
      ethylene/propylene copolymers with percentages of alternating EPE+PEP triads in
      the range of 61-76% at 50% ethylene incorporation. Both the nature of the
      substituent R and the bridge E influence the copolymerization behavior including
      the copolymerization activity, copolymer sequence distribution, molecular weight,
      and stereochemistry. Silicon-bridged metallocenes produce copolymers with higher
      activity and molecular weight but lower propylene incorporation at similar feeds
      than the carbon-bridged analogues. Isotactic PEPEP sequences were observed for
      all metallocenes, while the tacticities of the EPPE sequences varied with the
      bridge and the substituent on the metallocene ligand. Isotactic PEPEP sequences
      and atactic EPPE sequence errors in the alternating copolymers are consistent
      with a mechanism where the comonomers are enchained alternately at the
      heterotopic coordination sites of the metallocenes. Isotactic EPPE sequences are
      indicative of occasional multiple insertions at the stereospecific site, caused
      by an isomerization of the chain prior to monomer insertion (backskip).

PMID- 11572676
TI  - Acidity of carboxylic acids: a rebuttal and redefinition.
AB  - A recent theory of ionization of carboxylic acids divided the process of
      ionization into two steps and attributed the main importance to the electrostatic
      potential of the acid molecule. The origin of the acidity was thus seen in the
      high energy of the acid molecule and not in the stabilization of the anion by
      resonance. In this paper, the theory was revised on the basis of further
      calculations at an MP2/6-31++G(2d,p) level which followed in two steps the
      reverse process, protonation of the formate anion. The results were compared to
      those of the methanolate anion as reference. A contradictory conclusion was
      obtained: the reason for the acidity is in the electrostatic potential of the
      anion. As a model compound without resonance, 2,2,2-trifluoroethanol was
      investigated in the same way. The results were qualitatively similar, although
      any resonance in the anion is not possible. One can conclude that the acidity of
      carboxylic acids is due to the low energy of their anions; this follows
      unambiguously from the isodesmic reactions on the basis of either the
      experimental enthalpies of formation or the calculated energies. It is more
      difficult to decide whether this low energy is caused by resonance, because any
      model of the carboxylate anion without resonance is necessarily imperfect and the
      whole concept is not exactly defined. Several such models were reexamined and
      improved by separating the effect operative in the anion from those in the
      neutral acid molecule. While the electrostatic model did not allow any
      significant conclusion, two models based on VB calculation and on correlation
      analysis, respectively, furnished qualitatively concordant results: resonance in
      the anion is diminished by the resonance in the acid molecule, and both together
      are responsible for less than one-half of the acidity enhancement as compared to
      the acidity of alcohols. The ratio is reversed in water solution: resonance is
      then the more important factor responsible for some two-thirds of the enhanced
      acidity.

PMID- 11572677
TI  - Electronic properties of polyoxometalates: a DFT study of alpha/beta
      [XM(12)O(40)](n-) relative stability (M=W, Mo and X a main group element).
AB  - Keggin heteropolyanions [XM(12)O(40)](n-) have various isomeric structures, alpha
      and beta being the most common. Conventionally, the alpha structure appears to be
      the most stable, but calculations carried out at the DFT level for X = P(V),
      Si(IV), Al(III), As(V), Ge(IV), and Ga(III) and M = W(VI) and Mo(VI) show that
      this stability depends on several factors, particularly on the nature of the
      heteroatom (X) and the total charge of the cluster. In this paper, we apply the
      clathrate model to the Keggin molecule to carry out a fragment-interaction study
      to elucidate when and why the traditional relative stability of various isomers
      can be inverted. The fully oxidized anions that have inverted the traditional
      stability trend in this series are [AlW(12)O(40)](5-) and [GaW(12)O(40)](5-),
      both of which contain a third-group heteroatom and an overall charge of -5. beta
      isomers are always more easily reduced than alpha-isomers. This experimental
      observation suggests that reduction favors the stability of beta-isomers and one
      of the most important results of this study is that the alpha/beta inversion is
      achieved in most cases after the second reduction. The alpha- and beta-isomers
      may have different properties because the energy of the LUMO, a symmetry-adapted
      d(xy)-metal orbital, is different.

PMID- 11572678
TI  - Intramolecular, intermolecular, and heterogeneous nonadiabatic dissociative
      electron transfer to peresters.
AB  - The electron transfer to peresters was studied by electrochemical means in N,N
      dimethylformamide. The reduction was carried out by three independent methods:
      (i) heterogeneously, by using glassy carbon electrodes, (ii) homogeneously, by
      using electrogenerated radical anions as the donors, and (iii) intramolecularly,
      by using purposely synthesized donor-spacer-acceptor (D-Sp-A) systems.
      Convolution analysis of the heterogeneous data led to results in excellent
      agreement with the dissociative electron transfer theory. The homogeneous redox
      catalysis data also confirmed the reduction mechanism. The cyclic voltammetries
      of the D-Sp-A molecules could be simulated, leading to determination of the
      corresponding intramolecular dissociative rate constants. Analysis of the results
      showed that, regardless of the way by which the acceptor is reduced, the
      investigated dissociative electron transfers are strongly nonadiabatic and,
      particularly, that the experimental rates are several orders of magnitude smaller
      than the adiabatic limit. A possible mechanism responsible for the observed
      behavior is discussed.

PMID- 11572679
TI  - Negative-ion photoelectron spectroscopy, gas-phase acidity, and thermochemistry
      of the peroxyl radicals CH(3)OO and CH(3)CH(2)OO.
AB  - Methyl, methyl-d(3), and ethyl hydroperoxide anions (CH(3)OO(-), CD(3)OO(-), and
      CH(3)CH(2)OO(-)) have been prepared by deprotonation of their respective
      hydroperoxides in a stream of helium buffer gas. Photodetachment with 364 nm
      (3.408 eV) radiation was used to measure the adiabatic electron affinities:
      EA[CH(3)OO, X(2)A' '] = 1.161 +/- 0.005 eV, EA[CD(3)OO, X(2)A' '] = 1.154 +/-
      0.004 eV, and EA[CH(3)CH(2)OO, X(2)A' '] = 1.186 +/- 0.004 eV. The photoelectron
      spectra yield values for the term energies: Delta E(X(2)A' '-A (2)A')[CH(3)OO] =
      0.914 +/- 0.005 eV, Delta E(X(2)A' '-A (2)A')[CD(3)OO] = 0.913 +/- 0.004 eV, and
      Delta E(X(2)A' '-A (2)A')[CH(3)CH(2)OO] = 0.938 +/- 0.004 eV. A localized RO-O
      stretching mode was observed near 1100 cm(-1) for the ground state of all three
      radicals, and low-frequency R-O-O bending modes are also reported. Proton
      transfer kinetics of the hydroperoxides have been measured in a tandem flowing
      afterglow-selected ion flow tube (FA-SIFT) to determine the gas-phase acidity of
      the parent hydroperoxides: Delta(acid)G(298)(CH(3)OOH) = 367.6 +/- 0.7 kcal mol(
      1), Delta(acid)G(298)(CD(3)OOH) = 367.9 +/- 0.9 kcal mol(-1), and
      Delta(acid)G(298)(CH(3)CH(2)OOH) = 363.9 +/- 2.0 kcal mol(-1). From these
      acidities we have derived the enthalpies of deprotonation:
      Delta(acid)H(298)(CH(3)OOH) = 374.6 +/- 1.0 kcal mol(-1),
      Delta(acid)H(298)(CD(3)OOH) = 374.9 +/- 1.1 kcal mol(-1), and
      Delta(acid)H(298)(CH(3)CH(2)OOH) = 371.0 +/- 2.2 kcal mol(-1). Use of the
      negative-ion acidity/EA cycle provides the ROO-H bond enthalpies: DH(298)(CH(3)OO
      H) = 87.8 +/- 1.0 kcal mol(-1), DH(298)(CD(3)OO-H) = 87.9 +/- 1.1 kcal mol(-1),
      and DH(298)(CH(3)CH(2)OO-H) = 84.8 +/- 2.2 kcal mol(-1). We review the
      thermochemistry of the peroxyl radicals, CH(3)OO and CH(3)CH(2)OO. Using
      experimental bond enthalpies, DH(298)(ROO-H), and CBS/APNO ab initio electronic
      structure calculations for the energies of the corresponding hydroperoxides, we
      derive the heats of formation of the peroxyl radicals. The "electron
      affinity/acidity/CBS" cycle yields Delta(f)H(298)[CH(3)OO] = 4.8 +/- 1.2 kcal
      mol(-1) and Delta(f)H(298)[CH(3)CH(2)OO] = -6.8 +/- 2.3 kcal mol(-1).

PMID- 11572680
TI  - Chemistry of NO2 on oxide surfaces: formation of NO3 on TiO2(110) and NO2<-->O
      vacancy interactions.
AB  - Synchrotron-based high-resolution photoemission, X-ray absorption near-edge
      spectroscopy, and first-principles density functional (DF) slab calculations were
      used to study the interaction of NO(2) with a TiO(2)(110) single crystal and
      powders of titania. The main product of the adsorption of NO(2) on TiO(2)(110) is
      surface nitrate with a small amount of chemisorbed NO(2). A similar result is
      obtained after the reaction of NO(2) with polycrystalline powders of TiO(2) or
      other oxide powders. This trend, however, does not imply that the metal centers
      of the oxides are unreactive toward NO(2). An unexpected mechanism is seen for
      the formation of NO(3). Photoemission data and DF calculations indicate that the
      surface nitrate forms through the disproportionation of NO(2) on Ti sites
      (2NO(2,ads) --> NO(3,ads) + NO(gas)) rather than direct adsorption of NO(2) on O
      centers of titania. Complex interactions take place between NO(2) and O vacancies
      of TiO(2)(110). Electronic states associated with O vacancies play a predominant
      role in the bonding and surface chemistry of NO(2). The adsorbed NO(2), on its
      part, affects the thermochemical stability of O vacancies, facilitating their
      migration from the bulk to the surface of titania. The behavior of the
      NO(2)/titania system illustrates the importance of surface and subsurface defects
      when using an oxide for trapping or destroying NO(x)() species in the prevention
      of environmental pollution (DeNOx operations).

PMID- 11572681
TI  - Catalytic turnover of benzylamine by a model for the lysine tyrosylquinone (LTQ)
      cofactor of lysyl oxidase.
AB  - Lysyl oxidase differs from other copper amine oxidases in that its active quinone
      cofactor reflects cross-linking of a lysyl residue into the tyrosine-derived
      quinone nucleus found in the plasma and other copper amine oxidases. A model for
      the lysyl oxidase cofactor (LTQ), 3,3-dimethyl-2,3-dihydroindole-5,6-quinone (4),
      was synthesized and found to be stable to both hydrolysis and oxidation events
      that prevent simpler models from functioning as turnover catalysts. We show that
      4 catalyzes the aerobic oxidative deamination of benzylamine, though turnover
      eventually ceases on account of oxidation of the dihydrobenzoxazole tautomer of
      the "product Schiff base" to form a benzoxazole, a reaction that may be
      physiologically relevant. The mechanism of the overall reaction profile was
      elucidated by a combination of optical and NMR spectroscopy and O(2) uptake
      studies.

PMID- 11572682
TI  - Hybridization of PNA to structured DNA targets: quadruplex invasion and the
      overhang effect.
AB  - Peptide nucleic acid (PNA) probes have been synthesized and targeted to
      quadruplex DNA. UV-vis and CD spectroscopy reveal that the quadruplex structure
      of the thrombin binding aptamer (TBA) is disrupted at 37 degrees C by a short PNA
      probe. The corresponding DNA probe fails to bind to the stable secondary
      structure at this temperature. Thermal denaturation experiments indicate
      surprisingly high thermal and thermodynamic stabilities for the PNA-TBA hybrid.
      Our results point to the nonbonded nucleobase overhangs on the DNA as being
      responsible for this stability. This "overhang effect" is found for two different
      PNA-DNA sequences and a variety of different overhang lengths and sequences. The
      stabilization offered by the overhangs assists the PNA in overcoming the stable
      secondary structure of the DNA target, an effect which may be significant in the
      targeting of biological nucleic acids, which will always be much longer than the
      PNA probe. The ability of PNA to invade a structured DNA target expands its
      potential utility as an antigene agent or hybridization probe.

PMID- 11572683
TI  - Fluoroaromatic-fluoroaromatic interactions between inhibitors bound in the
      crystal lattice of human carbonic anhydrase II.
AB  - Intermolecular interactions of eleven different fluoroaromatic inhibitors are
      probed within the scaffolding of the crystal lattice of Phe-131-->Val carbonic
      anhydrase II. The degree and pattern of fluorine substitution on the inhibitor
      benzyl ring modulate its size, shape, and electronic character. In turn, these
      properties affect the geometry of intermolecular interactions between the
      fluoroaromatic rings of two different inhibitor molecules bound in the crystal
      lattice, as determined by X-ray crystallography. Depending on the degree and
      pattern of fluorine substitution, we observe a face-to-face (aromatic-aromatic)
      interaction, an atom-to-face (carbonyl-aromatic) interaction, or no interaction
      at all. These interaction geometries are analyzed with regard to van der Waals,
      electrostatic, and possible charge-transfer effects. For the aromatic-aromatic
      interactions investigated in this study, with aromatic ring quadrupoles
      specifically "tuned" by the degree and pattern of fluorination, the structural
      results suggest that London forces and charge-transfer complexation dominate over
      weakly polar electrostatic interactions in the association of aromatic ring
      pairs.

PMID- 11572684
TI  - Dihedral angles of trialanine in D2O determined by combining FTIR and polarized
      visible Raman spectroscopy.
AB  - We have measured the polarized visible Raman and FTIR spectra of trialanine and
      triglycine in D(2)O at acid, neutral, and alkaline pD. From the Raman spectra we
      obtained the isotropic and the anisotropic scattering. A self-consistent spectral
      analysis of the region between 1550 and 1800 cm(-1) was carried out to obtain the
      intensities, frequencies, and halfwidths of the respective amide I bands. A model
      was developed by means of which the intensity ratios of the amide I bands in all
      spectra and the respective frequency differences were utilized to determine the
      orientational angle theta between the peptide groups and the strength of
      excitonic coupling between the corresponding amide I modes. By exploiting results
      from a recent ab initio study on triglycine (Torii, H; Tasumi, M. J. Raman
      Spectrosc. 1998, 29, 81), we used these parameters to determine the dihedral
      angles phi and psi between the peptide groups. Our results show that trialanine
      adopts a 3(1)-helical structure in D(2)O for all of its three protonation states.
      The structure is insensitive to the carboxylate protonation and changes only
      slightly with N-terminal protonation. Triglycine is structurally more
      heterogeneous in the zwitterionic and the cationic state. Our spectral analysis
      suggests that 3(1)-helices coexist with right-handed alpha-helical and/or with
      beta-turn conformations. The N-terminal protonation stabilizes the 3(1)
      structure. Our study provides compelling evidence that tripeptides adopt stable
      conformations in aqueous solution and that they are suitable model systems to
      investigate the initiation of secondary structure formation.

PMID- 11572686
TI  - Chemistry-structure-simulation or chemistry-simulation-structure sequences? The
      case of MIL-34, a new porous aluminophosphate.
AB  - A new aluminophosphate, MIL-34, is investigated from its as-synthesized structure
      to its calcined microporous form. Single-crystal X-ray diffraction measurements
      on the as-synthesized MIL-34 (Al(4)(PO(4))(4)OH x C(4)H(10)N, space group P-1, a
      = 8.701(3) A, b = 9.210(3) A, c = 12.385(3) A, alpha = 111.11(2) degrees, beta =
      101.42(2) degrees, gamma = 102.08(2) degrees, V = 863.8(4) A(3), Z = 2, R = 3.8%)
      reveal a 3-D open framework where Al atoms are in both tetrahedral and trigonal
      bipyramidal coordinations. It contains a 2-D pore system defined by eight rings
      where channels along [100] cross channels running along [010] and [110]. CBuA
      molecules are trapped at their intersection. (27)Al, (31)P, and (1)H MAS NMR
      spectroscopies corroborate these structural features. Calcination treatments of a
      powder sample of the as-synthesized MIL-34 indicate its transformation into the
      related template-free structure that is stable up to 1000 degrees C. Lattice
      energy minimizations are then used in order to anticipate the crystal structure
      of the calcined MIL-34, starting with the knowledge of the as-synthesized
      structure exclusively. Energy minimizations predict a new regular zeotype
      structure (AlPO(4), space group P-1, a = 8.706 A, b = 8.749 A, c = 12.768 A,
      alpha = 111.17 degrees, beta = 97.70 degrees, gamma = 105.14 degrees, V = 846.75
      A(3), Z = 2) together with a thermodynamic stability similar to that of existing
      zeotype AlPOs. Excellent agreement is observed between the diffraction pattern
      calculated from the predicted calcined MIL-34 and the experimental X-ray powder
      diffraction pattern of the calcined sample. Finally, the atomic coordinates and
      cell parameters of the calcined MIL-34 predicted from the simulations are used to
      perform the Rietveld refinement of the calcined sample powder pattern, further
      corroborated by (27)Al and (31)P NMR measurements. This unique combination of
      experiment and simulation approaches is an interesting and innovative strategy in
      materials sciences, where simulations articulate the prediction of a possible
      template-free framework from its as-synthesized templated form. This is
      especially valuable when straightforward characterizations of the solid of
      interest with conventional techniques are not easy to carry out.

PMID- 11572685
TI  - Self-assembly with postmodification: kinetically stabilized metalla
      supramolecular rectangles.
AB  - Interaction of a predesigned molecular "clip" (4) with rigid dipyridyl bridging
      ligands, in acetone/water mixtures, leads to the formation of molecular
      rectangles (5-8) in 92-97% isolated yields via spontaneous self-assembly.
      Characterization was accomplished with multinuclear NMR and UV-vis spectroscopy,
      FAB mass spectrometry, and X-ray crystallography. The length of these
      metallamacrocycles ranges from 2 to 3 nm. Postmodification via non-nucleophilic
      counterion exchange results in enhanced structural integrity for the assemblies.

PMID- 11572687
TI  - A comparison of the influences of alkoxide and thiolate ligands on the electronic
      structure and reactivity of molybdenum(3+) and tungsten(3+) complexes.
      preparation and structures of M(2)(O(T)Bu)(2)(S(t)Bu)(4), [Mo(S(t)Bu)(3)(NO)](2),
      and W(S(t)Bu)(3)(NO)(py).
AB  - M(2)(O(t)Bu)(6) compounds (M = Mo, W) react in hydrocarbon solvents with an
      excess of (t)BuSH to give M(2)(O(t)Bu)(2)(S(t)Bu)(4), red, air- and temperature
      sensitive compounds. (1)H NMR studies reveal the equilibrium M(2)(O(t)Bu)(6) +
      4(t)BuSH <==> M(2)(O(t)Bu)(2)(S(t)Bu)(4) + 4(t)BuOH proceeds to the right slowly
      at 22 degrees C. The intermediates M(2)(O(t)Bu)(4)(S(t)Bu)(2),
      M(2)(O(t)Bu)(3)(S(t)Bu)(3), and M(2)(O(t)Bu)(5)(S(t)Bu) have been detected. The
      equilibrium constants show the M-O(t)Bu bonds to be enthalpically favored over
      the M-S(t)Bu bonds. In contrast to the M(2)(O(t)Bu)(6) compounds,
      M(2)(O(t)Bu)(2)(S(t)Bu)(4) compounds are inert with respect to the addition of
      CO, CO(2), ethyne, (t)BuC triple bond CH, MeC triple bond N, and PhC triple bond
      N. Addition of an excess of (t)BuSH to a hydrocarbon solution of
      W(2)(O(t)Bu)(6)(mu-CO) leads to the rapid expulsion of CO and subsequent
      formation of W(2)(O(t)Bu)(2)(S(t)Bu)(4). Addition of an excess of (t)BuSH to
      hydrocarbon solutions of [Mo(O(t)Bu)(3)(NO)](2) and W(O(t)Bu)(3)(NO)(py) gives
      the structurally related compounds [Mo(S(t)Bu)(3)(NO)](2) and
      W(S(t)Bu)(3)(NO)(py), with linear M-N-O moieties and five-coordinate metal atoms.
      The values of nu(NO) are higher in the related thiolate compounds than in their
      alkoxide counterparts. The bonding in the model compounds M(2)(EH)(6),
      M(2)(OH)(2)(EH)(4), (HE)(3)M triple bond CMe, and W(EH)(3)(NO)(NH(3)) and the
      fragments M(EH)(3), where M = Mo or W and E = O or S, has been examined by DFT
      B3LYP calculations employing various basis sets including polarization functions
      for O and S and two different core potentials, LANL2 and relativistic CEP. BLYP
      calculations were done with ZORA relativistic terms using ADF 2000. The
      calculations, irrespective of the method used, indicate that the M-O bonds are
      more ionic than the M-S bonds and that E ppi to M dpi bonding is more important
      for E = O. The latter raises the M-M pi orbital energies by ca. 1 eV for
      M(2)(OH)(6) relative to M(2)(SH)(6). For M(EH)(3) fragments, the metal
      d(xz)(),d(yz)() orbitals are destabilized by OH ppi bonding, and in
      W(EH)(3)(NO)(NH(3)) the O ppi to M dpi donation enhances W dpi to NO pi* back
      bonding. Estimates of the bond strengths for the M triple bond M in M(2)(EH)(6)
      compounds and M triple bond C in (EH)(3)M triple bond CMe have been obtained. The
      stronger pi donation of the alkoxide ligands is proposed to enhance back-bonding
      to the pi* orbitals of alkynes and nitriles and facilitate their reductive
      cleavage, a reaction that is not observed for their thiolate counterpart.

PMID- 11572688
TI  - Theoretical study of the mechanisms of substrate recognition by catalase.
AB  - A variety of theoretical methods including classical molecular interaction
      potentials, classical molecular dynamics, and activated molecular dynamics have
      been used to analyze the substrate recognition mechanisms of peroxisomal catalase
      from Saccharomyces cerevisiae. Special attention is paid to the existence of
      channels connecting the heme group with the exterior of the protein. On the basis
      of these calculations a rationale is given for the unique catalytic properties of
      this enzyme, as well as for the change in enzyme efficiency related to key
      mutations. According to our calculations the water is expected to be a
      competitive inhibitor of the enzyme, blocking the access of hydrogen peroxide to
      the active site. The main channel is the preferred route for substrate access to
      the enzyme and shows a cooperative binding to hydrogen peroxide. However, the
      overall affinity of the main channel for H(2)O(2) is only slightly larger than
      that for H(2)O. Alternative channels connecting the heme group with the monomer
      interface and the NADP(H) binding site are detected. These secondary channels
      might be important for product release.

PMID- 11572689
TI  - Real time reaction dynamics in carbon nanotubes.

PMID- 11572690
TI  - Mg2+-induced thermal enediyne cyclization at ambient temperature.

PMID- 11572691
TI  - Chain length-dependent three-dimensional organization of molecular rods with
      flexible coils.

PMID- 11572692
TI  - EELS and 13C NMR characterization of pure Ti2@C80 metallofullerene.

PMID- 11572693
TI  - Design of a hole-trapping nucleobase: termination of DNA-mediated hole transport
      at N2-cyclopropyldeoxyguanosine.

PMID- 11572694
TI  - Stopped-flow infrared spectroscopy reveals a six-coordinate intermediate in the
      formation of the proximally bound five-coordinate NO adduct of cytochrome c'.

PMID- 11572695
TI  - Magnetic behavior of a 3:2 mixture of bis(hexafluoroacetylacetonato)copper(II)
      and 1,3,5-benzenetriyltris(4-pyridyldiazomethane) in a frozen solution after
      irradiation: photochemical formation of a solid solution magnet.

PMID- 11572696
TI  - A simple, mild, catalytic, enantioselective addition of terminal acetylenes to
      aldehydes.

PMID- 11572697
TI  - Chemistry and optoelectronic properties of stacked supramolecular entities of
      trinuclear gold(I) complexes sandwiching small organic acids.

PMID- 11572699
TI  - Hydrozirconation of stannylacetylenes: a novel and highly efficient synthesis of
      1,1-diiodo-, 1,1-dibromo-, and mixed (Z)- or (E)-1-iodo-1-bromo-1-alkenes using
      1,1-hetero-bimetallic reagents.

PMID- 11572698
TI  - Annulation of aromatic imines via directed C-H activation with Wilkinson's
      catalyst.

PMID- 11572700
TI  - Synthesis of alpha-amido ketones via organic catalysis: thiazolium-catalyzed
      cross-coupling of aldehydes with acylimines.

PMID- 11572701
TI  - Nucleophilic substitutions on silane cation radicals: stepwise or concerted?

PMID- 11572702
TI  - Scandium cycloheptanitride, ScN(7): a predicted high-energy molecule containing
      an [eta(7)-N(7)](3-) ligand.

PMID- 11572703
TI  - High oxidation-state (formally d(0)) tungsten silylene complexes via double Si-H
      bond activation.

PMID- 11572704
TI  - Gas-phase catalytic oxidation of CO by Au(2-).

PMID- 11572705
TI  - Total synthesis of kaitocephalin, the first naturally occurring AMPA/KA receptor
      antagonist.

PMID- 11572706
TI  - Enantioselective conjugate addition of organomagnesium amides to
      enamidomalonates: synthesis of either enantiomer of beta-amino acid derivatives.

PMID- 11572707
TI  - H/D exchange reactions in dinuclear iron thiolates as activity assay models of Fe
      H2ase.

PMID- 11572708
TI  - Sol-gel derived nitric-oxide releasing materials that reduce bacterial adhesion.

PMID- 11572709
TI  - MMo(3)Se(3) (M = Li(+), Na(+), Rb(+), Cs(+), NMe(4)(+)) nanowire formation via
      cation exchange in organic solution.

PMID- 11572710
TI  - First cryptand-like calixpyrrole: synthesis, x-ray structure, and anion binding
      properties of a bicyclic[,3,3,3]nonapyrrole.

PMID- 11572711
TI  - Carbon-carbon bond activation in Pt(0)-diphenylacetylene complexes bearing
      chelating P,N- and P,P-ligands.

PMID- 11572712
TI  - Synthesis and characterization of the "missing" oxide of C(60): [5,6]-open
      C(60)O.

PMID- 11572715
TI  - A piece of my mind: futility.

PMID- 11572713
TI  - Determination of electron-transfer reorganization energy in nanometer-separated
      radical ion pair by time-resolved EPR spectroscopy.

PMID- 11572718
TI  - Type 2 diabetes mellitus in children: primary care and public health
      considerations.

PMID- 11572719
TI  - At the cloning circus sideshows abound, while scientists seek a wider audience.

PMID- 11572720
TI  - Epigenetics is seen as possible key to cloning.

PMID- 11572721
TI  - Gene mutation link with HIV resistance.

PMID- 11572726
TI  - From the World Health Organization: Health professionals must confront HIV/AIDS.

PMID- 11572727
TI  - Relationship between apolipoprotein E epsilon4 and sleep-disordered breathing at
      different ages.

PMID- 11572729
TI  - Breastfeeding and risk of overweight.

PMID- 11572730
TI  - Breastfeeding and risk of overweight.

PMID- 11572733
TI  - Safety of phthalates.

PMID- 11572736
TI  - Internet use among physicians, nurses, and their patients.

PMID- 11572737
TI  - Racial disparity in influenza vaccination: does managed care narrow the gap
      between African Americans and whites?
AB  - CONTEXT: Substantial racial disparities exist in use of some health services.
      Whether managed care could reduce racial disparities in the use of preventive
      services is not known. OBJECTIVE: To determine whether the magnitude of racial
      disparity in influenza vaccination is smaller among managed care enrollees than
      among those with fee-for-service insurance. DESIGN, SETTING, AND PARTICIPANTS:
      The 1996 Medicare Current Beneficiary Survey of a US cohort of 13 674 African
      American and white Medicare beneficiaries with managed care and fee-for-service
      insurance. MAIN OUTCOME MEASURES: Percentage of respondents (adjusted for
      sociodemographic characteristics, clinical comorbid conditions, and care-seeking
      attitudes) who received influenza vaccination and magnitude of racial disparity
      in influenza vaccination, compared among those with managed care and fee-for
      service insurance. RESULTS: Eight percent of the beneficiaries were African
      American and 11% were enrolled in managed care. Overall, 65.8% received influenza
      vaccination. Whites were substantially more likely to be vaccinated than African
      Americans (67.7% vs 46.1%; absolute disparity, 21.6%; 95% confidence interval
      [CI], 18.2%-25.0%). Managed care enrollees were more likely than those with fee
      for-service insurance to receive influenza vaccination (71.2% vs 65.4%;
      difference, 5.8%; 95% CI, 3.6%-8.3%). The adjusted racial disparity in fee-for
      service was 24.9% (95% CI, 19.6%-30.1%) and in managed care was 18.6% (95% CI,
      9.8%-27.4%). These adjusted racial disparities were both statistically
      significant, but the absolute percentage point difference in racial disparity
      between the 2 insurance groups (6.3%; 95% CI, -4.6% to 17.2%) was not.
      CONCLUSION: Managed care is associated with higher rates of influenza vaccination
      for both whites and African Americans, but racial disparity in vaccination is not
      reduced in managed care. Our results suggest that additional efforts are needed
      to adequately address this disparity.

PMID- 11572738
TI  - Validity of the Agency for Healthcare Research and Quality clinical practice
      guidelines: how quickly do guidelines become outdated?
AB  - CONTEXT: Practice guidelines need to be up-to-date to be useful to clinicians. No
      published methods are available for assessing whether existing practice
      guidelines are still valid, nor does any empirical information exist regarding
      how often such assessments need to be made. OBJECTIVES: To assess the current
      validity of 17 clinical practice guidelines published by the US Agency for
      Healthcare Research and Quality (AHRQ) that are still in circulation, and to use
      this information to estimate how quickly guidelines become obsolete. DESIGN,
      SETTING, AND PARTICIPANTS: We developed criteria for defining when a guideline
      needs updating, mailed surveys to members of the original AHRQ guideline panels
      (n = 170; response rate, 71%), and searched the literature for evidence through
      March 2000 (n = 6994 titles yielding 173 articles plus 159 new guidelines on the
      same topics). MAIN OUTCOME MEASURES: Identification of new evidence calling for a
      major, minor, or no update of the 17 guidelines; survival analysis of the rate at
      which guidelines became outdated. RESULTS: For 7 guidelines, new evidence and
      expert judgment indicated that a major update is required; 6 were found to be in
      need of a minor update; 3 were judged as still valid; and for 1 guideline, we
      could reach no conclusion. Survival analysis indicated that about half the
      guidelines were outdated in 5.8 years (95% confidence interval [CI], 5.0-6.6
      years). The point at which no more than 90% of the guidelines were still valid
      was 3.6 years (95% CI, 2.6-4.6 years). CONCLUSIONS: More than three quarters of
      the AHRQ guidelines need updating. As a general rule, guidelines should be
      reassessed for validity every 3 years.

PMID- 11572739
TI  - Low-density lipoprotein size, pravastatin treatment, and coronary events.
AB  - CONTEXT: Small low-density lipoprotein (LDL) particle size has been hypothesized
      to be a risk factor for coronary heart disease (CHD). Animal models link large
      LDL to atherosclerosis. However, the strong association between small LDL and
      other risk factors, particularly triglyceride levels, impedes determining whether
      LDL size independently predicts CHD in humans. OBJECTIVE: To examine whether LDL
      size is an independent predictor of recurrent coronary events in patients with
      known CHD, as opposed to a marker for other lipid abnormalities. DESIGN AND
      SETTING: Prospective, nested case-control study in the Cholesterol and Recurrent
      Events (CARE) trial, a randomized placebo-controlled trial of pravastatin
      conducted in 1989-1996. PARTICIPANTS: Survivors of myocardial infarction with
      typical LDL concentrations (416 cases and 421 controls). MAIN OUTCOME MEASURE:
      Subsequent myocardial infarction or coronary death during the 5-year follow-up,
      analyzed by quintile of LDL particle size and by treatment group. RESULTS:
      Overall, the mean LDL size was identical in cases and controls (25.6 nm). In
      patients in the placebo group, large LDL predicted coronary events in models
      adjusted only for age (relative risk [RR], 1.79; 95% confidence interval [CI],
      1.01-3.17) and for age and lipid and nonlipid risk factors (RR, 4.00; 95% CI,
      1.81-8.82), comparing those in the highest (mean, 26.6 nm) and lowest (mean, 24.5
      nm) quintiles of LDL size. This increased risk was not present in those taking
      pravastatin (age-adjusted analysis: RR, 0.98; 95% CI, 0.47-2.04; P =.046 for
      interaction for a difference in the effect of LDL size on coronary events between
      the placebo and treatment groups; multivariable analysis: RR, 1.33; 95% CI, 0.52
      3.38; P =.11 for interaction). CONCLUSIONS: Large LDL size was an independent
      predictor of coronary events in a typical population with myocardial infarction,
      but the adverse effect was not present among patients who were treated with
      pravastatin. Identifying patients on the basis of LDL size may not be useful
      clinically, since effective treatment for elevated LDL cholesterol concentrations
      also effectively treats risk associated with large LDL.

PMID- 11572740
TI  - Prevalence, donation practices, and risk assessment of blood donors with
      hemochromatosis.
AB  - CONTEXT: Despite changes in eligibility policies, practical barriers limit blood
      donations from individuals with hemochromatosis. Increased knowledge of
      hemochromatosis donor characteristics may help foster further changes that will
      promote more donations. OBJECTIVES: To estimate the prevalence of donors
      diagnosed as having hemochromatosis and to compare rates of unreported deferrable
      risks for transfusion-transmissible viral infections (TTVIs), positive screening
      test results for TTVIs, and donation patterns between hemochromatosis patient
      donors and donors reporting no medical conditions necessitating phlebotomy (non
      health-related donors). DESIGN: An anonymous mail survey conducted in 1998 as
      part of the ongoing Retrovirus Epidemiology Donor Study. SETTING AND
      PARTICIPANTS: Among a stratified probability sample of 92 581 blood donors from 8
      geographically diverse US blood centers, 52 650 (57%) responded. MAIN OUTCOME
      MEASURES: Prevalence of hemochromatosis among blood donors; prevalence of
      unreported deferrable risks and positive screening test results for TTVIs among
      hemochromatosis patient donors vs non-health-related donors. RESULTS: One hundred
      ninety-seven respondents (0.4%) identified themselves as hemochromatosis patients
      and 50 079 (95.1%) as non-health-related donors. An estimated 0.8% of all
      donations were from hemochromatosis patients, 45.8% of whom reported that they
      had donated blood to treat their illness. The proportion of repeat donors was
      higher in hemochromatosis patients than in non-health-related donors (83.5% vs
      76.5%; P =.03). Among repeat donors, 68.7% of hemochromatosis patients reported
      donating at least 3 times in the past year compared with 49.1% of non-health
      related donors (P<.001). The prevalence of unreported deferrable risks for TTVIs
      was similar in hemochromatosis patients (2.0%) and non-health-related
      donors(3.1%) as was the overall prevalence of positive screening test results
      (1.3% of hemochromatosis patients vs 1.6% of non-health-related donors).
      CONCLUSIONS: Although significant numbers of hemochromatosis patients reported
      donating blood for therapeutic reasons, our findings suggest that this population
      does not present a greater risk to blood safety than other donors.

PMID- 11572741
TI  - Cost-effectiveness of automated external defibrillators on airlines.
AB  - CONTEXT: Installation of automated external defibrillators (AEDs) on passenger
      aircraft has been shown to improve survival of cardiac arrest in that setting,
      but the cost-effectiveness of such measures has not been proven. OBJECTIVE: To
      examine the costs and effectiveness of several different options for AED
      deployment in the US commercial air transportation system. DESIGN, SETTING, AND
      SUBJECTS: Decision and cost-effectiveness analysis of a strategy of full
      deployment on all aircraft as well as several strategies of partial deployment
      only on larger aircraft, compared with a baseline strategy of no AEDs on aircraft
      (but training flight attendants in basic life support) for a hypothetical cohort
      of persons experiencing cardiac arrest aboard US commercial aircraft. Estimates
      for costs and outcomes were obtained from the medical literature, the Federal
      Aviation Administration, the Air Transport Association of America, a population
      based cohort of Medicare patients, AED manufacturers, and the Bureau of Labor
      Statistics. MAIN OUTCOME MEASURES: Quality-adjusted survival after cardiac
      arrest; costs of AED deployment on aircraft and of medical care for cardiac
      arrest survivors. RESULTS: Adding AEDs on passenger aircraft with more than 200
      passengers would cost $35 300 per quality-adjusted life-year (QALY) gained.
      Additional AEDs on aircraft with capacities between 100 and 200 persons would
      cost an additional $40 800 per added QALY compared with deployment on large
      capacity aircraft only, and full deployment on all passenger aircraft would cost
      an additional $94 700 per QALY gained compared with limited deployment on
      aircraft with capacity greater than 100. Sensitivity analyses indicated that the
      quality of life, annual mortality rate, and the effectiveness of AEDs in
      improving survival were the most influential factors in the model. In 85% of
      Monte Carlo simulations, AED placement on large-capacity aircraft produced cost
      effectiveness ratios of less than $50 000 per QALY. CONCLUSION: The cost
      effectiveness of placing AEDs on commercial aircraft compares favorably with the
      cost-effectiveness of widely accepted medical interventions and health policy
      regulations, but is critically dependent on the passenger capacity of the
      aircraft. Placing AEDs on most US commercial aircraft would meet conventional
      standards of cost-effectiveness.

PMID- 11572742
TI  - Endocrine function and oocyte retrieval after autologous transplantation of
      ovarian cortical strips to the forearm.
AB  - CONTEXT: In reproductive-age women, one of the common adverse effects of
      chemotherapy and radiotherapy is premature ovarian failure. In addition, a
      significant number of women experience early menopause due to oophorectomy
      performed for benign indications. OBJECTIVE: To develop an ovarian
      transplantation technique to preserve endocrine function in women undergoing
      sterilizing radiotherapy and/or chemotherapy, or oophorectomy. DESIGN AND
      SETTING: Case study of 2 patients in New York who received autologous ovarian
      transplantation (patient A, November 1999; patient B, April 2000) to the forearm
      prior to pelvic radiotherapy or after oophorectomy. PARTICIPANTS: Patient A is a
      35-year-old woman with stage IIIB squamous cell cervical carcinoma and patient B
      is a 37-year-old woman with recurrent benign ovarian serous cysts. MAIN OUTCOME
      MEASURES: Follicular development evident by ultrasound examination; cyclical
      production of estradiol and progesterone; restoration of serum follicle
      stimulating hormone, luteinizing hormone, and testosterone levels to
      nonmenopausal range; and disappearance of menopausal symptoms. RESULTS: Menopause
      was confirmed immediately after the transplantation in both patients by serum
      follicle-stimulating hormone measurements (patient A, 47 mIU/mL; patient B, 50.7
      mIU/mL). In patient A, follicle development was noted by physical and ultrasound
      examinations approximately 10 weeks after the transplantation. The mean (SE)
      follicle-stimulating hormone and luteinizing hormone levels decreased to 8.6
      (0.4) mIU/mL and 12.8 (0.8) mIU/mL, respectively. The peripheral estradiol levels
      showed cyclical variation (mean [SE], 115 [9.2] pg/mL [422 (33.8) pmol/L), and
      during the 18-month follow-up, a dominant follicle developed each month. The
      estradiol levels from the right cubital vein were consistent with ovarian vein
      measurements (mean [SE], 1069 [269] pg/mL [3924 (987.5) pmol/L]). Percutaneous
      oocyte aspirations yielded a mature oocyte. In patient B, ovarian function was
      demonstrated by ultrasound visualization of a 9-mm follicle by 6 months after
      transplantation. Thereafter, the patient had spontaneous menstruation every 25 to
      28 days. Ovulation was further confirmed by midluteal progesterone measurements
      (range, 7-10.1 ng/mL; mean [SE], 8.5 [0.9] ng/mL). Patient B's ovarian graft was
      still functional 10 months after the transplantation. CONCLUSIONS: Subcutaneous
      ovarian transplantation appears to be a relatively simple, novel technique to
      preserve endocrine function in women undergoing sterilizing cancer therapy or
      surgery.

PMID- 11572743
TI  - Comparison of 2 methods for calculating adjusted survival curves from
      proportional hazards models.
AB  - CONTEXT: Adjusted survival curves are often presented in medical research
      articles. The most commonly used method for calculating such curves is the mean
      of covariates method, in which average values of covariates are entered into a
      proportional hazards regression equation. Use of this method is widespread
      despite published concerns regarding the validity of resulting curves. OBJECTIVE:
      To compare the mean of covariates method to the less widely used corrected group
      prognosis method in an analysis evaluating survival in patients with and without
      diabetes. In the latter method, a survival curve is calculated for each level of
      covariates, after which an average survival curve is calculated as a weighted
      average of the survival curves for each level of covariates. DESIGN, SETTING, AND
      PATIENTS: Analysis of cohort study data from 11 468 Alberta residents undergoing
      cardiac catheterization between January 1, 1995, and December 31, 1996. MAIN
      OUTCOME MEASURES: Crude and risk-adjusted survival for up to 3 years after
      cardiac catheterization in patients with vs without diabetes, analyzed by the
      mean of covariates method vs the corrected group prognosis method. RESULTS:
      According to the mean of covariates method, adjusted survival at 1044 days was
      94.1% and 94.9% for patients with and without diabetes, respectively, with
      misleading adjusted survival curves that fell above the unadjusted curves. With
      the corrected group prognosis method, the corresponding survival values were
      91.3% and 92.4%, with curves that fell more appropriately between the unadjusted
      curves. CONCLUSIONS: Misleading adjusted survival curves resulted from using the
      mean of covariates method of analysis for our data. We recommend using the
      corrected group prognosis method for calculating risk-adjusted curves.

PMID- 11572744
TI  - A woman with an extremely premature newborn.

PMID- 11572745
TI  - Patient preferences and health disparities.

PMID- 11572746
TI  - Development and aftercare of clinical guidelines: the balance between rigor and
      pragmatism.

PMID- 11572752
TI  - Unintended consequences of artificial airways: replacement parts are never as
      good as the factory-installed.

PMID- 11572753
TI  - Tracheal-innominate artery fistula caused by the endotracheal tube tip: case
      report and investigation of a fatal complication of prolonged intubation.
AB  - CASE REPORT: A patient with extensive burns was intubated with an 8.0 mm internal
      diameter endotracheal tube (ETT) equipped with a subglottic suction port
      (Mallinckrodt HiLo Evac). The ETT was secured to a left upper molar with wire
      sutures throughout the hospitalization course to ensure airway stability. On the
      40th day of intubation, the patient exsanguinated and died from a tracheo
      innominate artery fistula. Postmortem examination revealed a 1 cm lesion of the
      left anterior tracheal wall at the position of the ETT tip. The prolonged
      stationary position of the ETT was considered the primary factor responsible for
      the fistula. Yet tracheo-innominate artery fistula normally is associated with
      high cuff pressures rather than with the tube tip. The special ETT construction
      required for the subglottic suction feature was suspected to have increased tube
      rigidity and may have played a contributory role. METHODS: The rigidity of the
      Mallinckrodt HiLo Evac was measured with a mechanical model and compared to 5
      other commercially-available ETTs. Rigidity was expressed as the force generated
      by the ETT tip when the tube curvature was altered by 5 cm and 10 cm of flexion
      from its resting position. RESULTS: The mean force exerted by the Mallinckrodt
      HiLo Evac was 10.1 +/- 2.8 g at 5 cm of flexion and 17.7 +/- 5.1 g at 10 cm of
      flexion. This was significantly greater than all other ETT brands tested (by one
      way analysis of variance and Student-Newman-Kuels test, p < 0.05). CONCLUSION:
      This case of fatal tracheo-innominate artery fistula formation associated with an
      ETT tip was unusual because of the extended duration of endotracheal intubation
      and the complexity of the patient's airway management problems. Our data suggest
      that the higher rigidity of the HiLo Evac ETT may have contributed to fistula
      development at the tube tip. However, we do not believe that the higher rigidity
      of the HiLo Evac ETT necessarily poses any greater risk than other ETTs under
      normal circumstances, in which the tube tip is not fixed in a stationary position
      for an extended period.

PMID- 11572754
TI  - Airway pressure release ventilation with a short release time in a child with
      acute respiratory distress syndrome.
AB  - Airway pressure release ventilation (APRV) allows ventilation and oxygenation to
      occur at lower peak and mean airway pressures than conventional positive pressure
      ventilation. The use of APRV in adults is an effective method of ventilation for
      patients with acute lung injury and acute respiratory distress syndrome. However,
      the use of APRV in children is less established. We report the use of APRV with a
      short release time of 0.2 s in a child with acute respiratory distress syndrome
      secondary to respiratory syncytial virus pneumonia.

PMID- 11572755
TI  - Implementation of a low tidal volume ventilation protocol for patients with acute
      lung injury or acute respiratory distress syndrome.
AB  - The ARDS (acute respiratory distress syndrome) Network study found 22% lower
      mortality in acute lung injury and ARDS patients ventilated with low tidal
      volumes (V(T)) than in those ventilated with traditional V(T) ventilation.
      Several points should be considered when using the low V(T) protocol for clinical
      practice. Prior to implementation, hemodynamic and acid-base status, minute
      ventilation, and adequacy of sedation should be assessed to minimize the
      potential for intolerance. The volume-preset, assist-control mode is recommended
      for better control of V(T), and the respiratory rate should be increased as V(T)
      is reduced, so as to maintain minute ventilation and prevent acute hypercapnia.
      When unavoidable, hypercapnia should be induced slowly. Ventilator inspiratory
      flow (V(I)) and trigger sensitivity settings should be optimized to limit the
      increase in work of breathing and dyspnea. When dyspnea results in double
      triggered breaths, V(T) can be titrated to 7-8 mL/kg, provided end-inspiratory
      plateau pressure is < or = 30 cm H(2)O. In severe acidosis (pH < 7.15) V(T) also
      can be increased. However, every effort should be made to maintain plateau
      pressure and V(T) goals by buffering severe acidosis and treating patient
      ventilator asynchrony with sedation. Evaluation for weaning should occur when
      adequate oxygenation can be maintained on 40% oxygen and a positive end
      expiratory pressure of 8 cm H(2)O. Pressure support levels between 5 and 20 cm
      H(2)O (above 5 cm H(2)O positive end-expiratory pressure) are used for weaning
      and titrated to keep the respiratory rate < 35 breaths/min. Pressure support
      levels should be weaned aggressively, as long as the protocol's weaning tolerance
      criteria can be maintained.

PMID- 11572756
TI  - Decision analysis for large capital purchases: how to buy a ventilator.
AB  - We describe a formal decision-making procedure for purchasing intensive care
      ventilators. We adapted a general decision-making tool known as an additive,
      compensatory, multiattribute utility model. The model incorporates input from the
      various stakeholders in the decision. It identifies the factors that are
      important in the decision and the alternative decision options, weights the
      factors, ranks the alternative decisions on how well they serve the factors, and
      finally provides an overall score that identifies the best option. This model
      provides a more objective and analytical approach than is often used in
      purchasing decisions. The benefits include simplifying discussion among
      stakeholders and assisting administrators in justifying major purchase proposals.

PMID- 11572757
TI  - Epstein-Barr virus-associated gastric carcinoma in Japanese Brazilians and non
      Japanese Brazilians in Sao Paulo.
AB  - The proportion of Epstein-Barr virus-associated gastric carcinoma (EBV-GC) was
      examined in 149 Japanese-Brazilian and 151 non-Japanese-Brazilian gastric
      carcinoma cases using in situ hybridization (ISH) assay to detect EBV-encoded
      small RNA (EBER), and the results were compared with our referent Japanese data.
      We found that 4.7% of cases in Japanese Brazilians were EBER-positive. This
      frequency was slightly lower than that of the referent Japanese, among whom 6.2%
      of 2038 gastric-carcinoma cases were EBER-positive. On the other hand, the non
      Japanese-Brazilian series showed a significantly higher proportion of EBV-GC
      (11.2%) than the referent group did (P = 0.01). Although EBV-GC was predominant
      in males among non-Japanese Brazilians (M / F = 3.6, P = 0.047), as was the case
      in Japanese (M / F = 2.7), Japanese Brazilians did not show such a male
      predominance. The sex-ratio difference between the Japanese Brazilians and
      Japanese was statistically significant (P = 0.005). In conclusion, the present
      study in Japanese Brazilians and Japanese yielded no evidence suggesting any
      change in the frequency of EBV-GC caused by migration, except the absence of male
      predominance, which was observed both in Japanese and non-Japanese Brazilians.

PMID- 11572758
TI  - Geranylgeraniol, an intermediate product in mevalonate pathway, induces apoptotic
      cell death in human hepatoma cells: death receptor-independent activation of
      caspase-8 with down-regulation of Bcl-xL expression.
AB  - Geranylgeraniol (GGOH), an intermediate of mevalonate metabolism, is known to
      induce apoptosis in various lines of cancer cells. The present study was
      undertaken to clarify the signaling pathways of apoptosis induced by GGOH in
      human hepatoma cells. HuH-7 human hepatoma cells were incubated in the absence or
      presence of GGOH. Activation of caspase-8 /-9 /-3 in HuH-7 cells was found after
      8 h treatment with GGOH, at which time DNA fragmentation and loss of
      mitochondrial transmembrane potential (Deltaphim) occurred. HuH-7 cells do not
      express Bcl-2; however, down-regulation of Bcl-xL expression preceded activation
      of the caspase cascade in GGOH-treated HuH-7 cells, while Bax expression was not
      changed by GGOH treatment. Addition of caspase inhibitors restored the decreased
      cell viability of HuH-7 cells by GGOH, including Deltaphim, to the baseline
      level, which indicated that caspase triggers mitochondria-dependent apoptotic
      pathways in GGOH-treated HuH-7 cells. Similarly, GGOH-mediated apoptosis of HuH-7
      cells was clearly prevented by coadministration of ursodeoxycholic acid (UDCA),
      which led to restoration of the level of Bcl-xL expression. Activation of caspase
      8 /-9 /-3, as well as Deltaphim, by GGOH treatment was suppressed by addition of
      UDCA. Our results indicate that activation of the caspase cascade initiating from
      caspase-8, which could be accelerated by down-regulation of Bcl-xL expression,
      plays a key role in an apoptotic process induced by GGOH in human hepatoma cells.

PMID- 11572759
TI  - Expression of 5alpha-reductases in human epithelial ovarian cancer: its
      correlation with androgen receptor status.
AB  - Androgen metabolism and possible actions are considered to play some roles in
      human epithelial ovarian neoplasms, but the details have not been well studied.
      We have examined the expression of 5alpha-reductase type 1 and type 2, which
      catalyze the conversion of testosterone to more active androgen, 5alpha
      dehydrotestosterone, and androgen receptor (AR), using immunohistochemistry (104
      cases) and reverse transcription-polymerase chain reaction (RT-PCR) (16 cases) as
      a first step toward understanding the metabolism and possible actions of
      androgens in human common epithelial ovarian carcinoma. 5alpha-Reductase type 1
      was immunopositive in 75 / 104 cases (72.0%), and 5alpha-reductase type 2 in 52 /
      104 cases (50.0%) (P < 0.001). There was no significant correlation between
      patterns of immunolocalization and clinicopathological parameters examined.
      Median labeling index (LI) for AR was 17.8% (range 0 - 84.4%) which was
      significantly higher in serous carcinoma than other histological types (P <
      0.001). There was a significant positive correlation between 5alpha-reductase
      type 1 immunoreactivity and AR LI (P = 0.0027), but no significant correlation
      was detected in 5alpha-reductase type 2. Results of RT-PCR analysis were also
      consistent with those of immunohistochemistry. The relatively wide distribution
      of 5alpha-reductase type 1, and its correlation to AR status in human epithelial
      ovarian malignancies suggest that this isozyme plays important roles in androgen
      metabolism and actions in these tumors.

PMID- 11572761
TI  - Involvement of c-Src in carcinoma cell motility and metastasis.
AB  - Carcinoma cells exhibit dysfunction / dysregulation of cell adhesion systems that
      correlates with their abilities to migrate, invade, and metastasize. Here we show
      that the tyrosine kinase c-Src is required for motility and metastasis of two
      carcinoma cell lines. Adherent KYN-2 cells having a high level of c-Src kinase
      activity become scattered, extend lamellipodia, and exhibit high motility.
      Expression of a dominant-negative mutant form of c-Src caused formation of stress
      fibers and focal adhesions, and markedly reduced motility. HCT15 cells extended
      lamellipodia and became scattered in response to lysophosphatidic acid
      stimulation in parallel with transient activation of c-Src, which was inhibited
      by expression of a dominant-negative mutant form of c-Src or treatment with a
      specific Src kinase inhibitor. Furthermore, implantation of dominant-negative c
      Src transfectants into the peritoneal cavity of SCID mice resulted in reduced
      peritoneal dissemination compared with control transfectants. These findings
      indicate that c-Src activation is critically involved in carcinoma cell migration
      and metastasis.

PMID- 11572760
TI  - Heterogeneous breakpoints on the immunoglobulin genes are involved in fusion with
      the 5' region of BCL2 in B-cell tumors.
AB  - The 5' flanking region of the BCL2 gene (5'-BCL2) is a breakpoint cluster of
      rearrangements with immunoglobulin genes (IGs). In contrast to t(14;18)(q32;q21)
      affecting the 3' region of BCL2, 5'-BCL2 can fuse to not only the heavy chain
      gene (IGH), but also two light chain gene (IGL) loci. We report here cloning and
      sequencing of a total of eleven 5'-BCL2 / IGs junctional areas of B-cell tumors,
      which were amplified by long-distance polymerase chain reaction-based assays. The
      breakpoints on 5'-BCL2 were distributed from 378 to 2312 bp upstream of the
      translational initiation site and, reflecting the alteration of regulatory
      sequences of BCL2, 5'-BCL2 / IGs-positive cells showed markedly higher levels of
      BCL2 expression than those of t(14;18)-positive cells. In contrast, the
      breakpoints on the IGs were variable. Two 5'-BCL2 / IGH and two 5'-BCL2 /
      IGLkappa junctions occurred 5' of the joining (J) segments, suggesting operation
      of an erroneous variable (V) / diversity (D) / J and V / J rearrangement
      mechanism. However, two other 5'-BCL2 / IGH junctions affected switch regions,
      and the kappa-deleting element, which is located 24 kb downstream of the constant
      region of IGLkappa, followed the 5'-BCL2 in another case. One 5'-BCL2 / IGLkappa
      and two 5'-BCL2 / IGLlambda junctions involved intronic regions where the normal
      recombination process does not occur. In the remaining one case, the 5'-BCL2
      fused 3' of a Vlambda gene that was upstream of another Vlambda / Jlambda complex
      carrying a non-producing configuration, indicating that the receptor editing
      mechanism was likely involved in this rearrangement. Our study revealed
      heterogeneous anatomy of the 5'-BCL2 / IGs fusion gene leading to transcriptional
      activation of BCL2, and suggested that the mechanisms underlying the formation of
      this particular oncogene / IGs recombination are not identical to those of
      t(14;18).

PMID- 11572762
TI  - Epigenetic regulation of the KAI1 metastasis suppressor gene in human prostate
      cancer cell lines.
AB  - Expression of the KAI1 gene, a metastasis-suppressor for prostate cancer, is
      reduced in all foci of prostatic metastasis. The altered regulatory mechanism is
      not strongly related to mutations or allelic losses of the KAI1 gene in prostate
      tumors. Since transcriptional silencing of genes has been found to be caused by
      epigenetic mechanisms, we have investigated the involvement of this epigenetic
      regulation of KAI1 expression in prostate cancers. The methylation status of the
      KAI1 promoter region was examined by restriction-enzyme digestion and sequencing,
      after amplifying a 331-bp fragment in the GC-rich promoter region from 4 human
      prostate cancer cell lines treated with bisulfite. The same 4 cell lines were
      also exposed to various concentrations of the demethylating agent, 5-aza-2'
      deoxycytidine (5-AzaC) and / or the histone deacetylase inhibitor, trichostatin A
      (TSA). To clarify the influence of epigenetic modification on reduced KAI1 mRNA
      expression in the tumor cells, RT-PCR and northern-blot analyses were performed.
      Bisulfite-sequencing data showed a few methylated CpG islands in the promoter. RT
      PCR analysis of 5-AzaC and / or TSA-treated cells indicated reversal of
      suppression of KAI1 transcription in two cell lines (PC-3 and DU-145), although
      the expression could not be detected by northern blots. From these results, it is
      suggested that epigenetic change is not the main mechanism of KAI1 down
      regulation, though there remains a possibility that methylation in a more
      upstream region might be associated with this regulation.

PMID- 11572763
TI  - Mitotic checkpoint protein hsMAD2 as a marker predicting liver metastasis of
      human gastric cancers.
AB  - hsMAD2, the human homologue of mitotic arrest deficient 2 (MAD2), is a key
      component of the mitotic checkpoint system. Recently, mutations and decreased
      expression of mitotic checkpoint genes including hsMAD2 have been reported in
      cancer cell lines with defective mitotic checkpoint. However, the genetic
      alterations in the genomic hsMAD2 gene have not been determined in gastric
      cancers. Moreover, the biological implications of the overexpressed hsMAD2 in
      primary cancers are unknown. In this study, we analyzed 32 primary gastric
      cancers with polymerase chain reaction (PCR) amplification of all exons,
      including flanking intronic sequences, of the genomic hsMAD2 gene followed by
      direct DNA sequencing. We also measured the hsMAD2 protein levels in cancer and
      normal tissues by semi-quantitative immunoblotting. No mutations were found in
      the coding sequences, although three single nucleotide polymorphisms (SNPs) were
      identified in the noncoding sequences in 13 of 32 patients. These SNPs were not
      associated with either hsMAD2 expression or disease progression. The semi
      quantitative western blot analysis showed hsMAD2 was significantly overexpressed
      in gastric cancer tissues compared with corresponding normal tissues (P < 0.001).
      The calculated ratio of the hsMAD2 protein in cancer tissue (C) to that in
      corresponding normal tissue (N) (C / N ratio) was significantly higher in
      patients with well differentiated adenocarcinoma (P = 0.0274) or with synchronous
      liver metastasis (P = 0.0025). A C / N ratio greater than 3 was observed more
      frequently in patients with synchronous liver metastasis. Therefore, C / N ratio
      > 3 may be clinically important as a predictive indicator for metachronous liver
      metastasis of gastric cancers.

PMID- 11572765
TI  - Altered topoisomerase IIalpha and multidrug resistance-associated protein levels
      during drug selection: adaptations to increasing drug pressure.
AB  - To understand resistance to topoisomerase II inhibitors, we used four cancer cell
      lines (ZR-75B, MDA-MB-231, T47D, and MCF-7) and performed a single-step selection
      process to isolate 50 clones resistant to topoisomerase II inhibitors. Of these,
      26 were isolated with VP-16 and 24 with mAMSA. Sixteen of these isolates (four
      from each cell line; two selected with VP-16 and two with mAMSA) were further
      exposed to higher drug concentrations. Characterization of the resistant sublines
      revealed the adaptation that occurs with increasing drug concentration during in
      vitro selections. Reduced topoisomerase IIalpha mRNA level was observed in the
      majority of the initial isolates. This reduction was accompanied by a decrease in
      topoisomerase II activity. Other isolates showed increased levels of multidrug
      resistance-associated protein (MRP). With advancing resistance, MRP expression
      was increased further, concomitantly with some recovery in topoisomerase IIalpha
      expression and topoisomerase II activity. In these sublines, high levels of
      resistance were attained as a result of synergism between the reduced
      topoisomerase IIalpha levels and MRP overexpression. These results extend
      previous studies demonstrating how cellular adaptation to increasing drug
      pressure utilizes more than one mechanism. Reduced expression of topoisomerase
      IIalpha occurs early in the selection process. MRP overexpression can occur early
      or can help to confer high levels of resistance. In the latter case, MRP
      overexpression allows some recovery of topoisomerase II activity without loss of
      high drug resistance.

PMID- 11572764
TI  - PI3-kinase p85alpha is a target molecule of proline-rich antimicrobial peptide to
      suppress proliferation of ras-transformed cells.
AB  - PR-39, which is an endogenous antimicrobial peptide, can bind to Src homology 3
      domains of the NADPH complex protein p47(phox) and the signaling adapter protein
      p130(Cas). Recently, we have reported that PR-39 gene transduction altered
      invasive activity and actin structure of human hepatocellular carcinoma cells,
      suggesting that this peptide affects cellular signaling due to its proline-rich
      motif. In order to clarify the mechanism of the PR-39 functions, we transfected
      the PR-39 gene into mouse NIH3T3 cells which had already been transformed with
      human activated k-ras gene. The PR-39 gene transfectant showed a reorganization
      of actin structure and suppression of cell proliferation both in vitro and in
      vivo. Decreases of MAP (mitogen-activated protein) kinase activity, cyclin D1
      expression and JNK activity were observed in the PR-39 gene transfectant. Co
      immunoprecipitation analysis revealed that PR-39 binds to PI3-kinase p85alpha,
      which is a regulatory subunit of PI3-kinase and one of the effectors by which ras
      induces cytoskeletal changes and stimulates mitogenesis. The PI3-kinase activity
      of the PR-39 gene transfectant was decreased compared with that of the ras
      transformant. These results suggest that PR-39 alters actin structure and cell
      proliferation rate by binding to PI3-kinase p85alpha and suppressing the PI3
      kinase activity.

PMID- 11572766
TI  - Close correlation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate, an
      intracellular active metabolite, to the therapeutic efficacy of N(4)-behenoyl-1
      beta-D-arabinofuranosylcytosine therapy for acute myelogenous leukemia.
AB  - N(4)-Behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC), a prodrug of 1-beta-D
      arabinofuranosylcytosine, is used effectively for the treatment of leukemia in
      Japan. BHAC therapy may be more effective if it is delivered in conjunction with
      monitoring of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP), the
      intracellular active metabolite of ara-C derived from BHAC. However, previous
      monitoring methods for ara-CTP were insufficiently sensitive. Here, using our new
      sensitive method, we evaluated the ara-CTP pharmacokinetics in relation to the
      therapeutic response in 11 acute myelogenous leukemia patients who received a 2-h
      infusion of BHAC (70 mg / m(2)) in combination remission induction therapy. ara
      CTP could be monitored at levels under 1 mM. BHAC maintained effective levels of
      plasma ara-C and intracellular ara-CTP for a longer time, even compared with
      historical values of high-dose ara-C. The area under the concentration-time curve
      of ara-CTP was significantly greater in the patients with complete remission than
      in the patients without response. This greater amount of ara-CTP was attributed
      to the higher ara-CTP concentrations achieved in the responding patients. There
      was no apparent difference of plasma ara-C pharmacokinetics between the two
      groups. Thus, for the first time, the ara-CTP pharmacokinetics was evaluated in
      relation to the therapeutic effect of BHAC, and the importance of ara-CTP was
      proven. Administration of optimal BHAC therapy may require monitoring of the ara
      CTP pharmacokinetics in each individual patient.

PMID- 11572767
TI  - Augmented adriamycin sensitivity in cells transduced with an antisense tumor
      necrosis factor gene is mediated by caspase-3 downstream from reactive oxygen
      species.
AB  - While transduction of an antisense tumor necrosis factor (TNF) gene sequence can
      augment the cytotoxicity of adriamycin (ADM) in human cancer cells, the specific
      effect of introducing this sequence on the signal transduction pathway leading to
      cell death remains unclear. In ADM-resistant pancreatic carcinoma (PANC-1) cells,
      both the antioxidant N-acetyl-L-cysteine (NAC) and the caspase-3 inhibitor acetyl
      L-aspartyl-L-methionyl-L-glutaminyl-L-aspartyl-aldehyde (Ac-DMQD-CHO) prevented
      ADM-induced cytotoxicity. NAC additionally inhibited caspase-3 activity induced
      by ADM treatment, while Ac-DMQD-CHO showed no suppressive effect on reactive
      oxygen species (ROS). Stable antisense-TNF transfectants showed higher ADM
      sensitivity and greater ADM-induced ROS production and caspase-3 activity than
      mock transfectant or parent cells. These results indicate that increased caspase
      3 activity downstream from ROS production is among the mechanisms by which
      transduction of the antisense TNF sequence of augments ADM sensitivity of
      pancreatic carcinoma cells.

PMID- 11572768
TI  - Pharmacokinetic study of a gallium-porphyrin photo- and sono-sensitizer, ATX-70,
      in tumor-bearing mice.
AB  - The tissue distribution of a gallium-porphyrin photo- and sono-sensitizer, 7,12
      bis(1-decyloxyethyl)-Ga(III)-3,8,13,17-tetramethylporphyrin-2,18
      dipropionyldiaspartic acid, ATX-70, was pharmacokinetically examined in tumor
      bearing mice. The drug was administered intravenously to CDF(1) mice implanted
      with Colon 26 carcinoma. Blood and tissue samples were collected for up to 72 h
      after administration. The drug concentration was determined by high-performance
      liquid chromatography (HPLC) with fluorescence detection. ATX-70 was found to
      accumulate in tumors at a relatively high concentration that peaked between 2 h
      and 6 h after administration. However, modest concentrations of ATX-70 also
      remained in healthy tissues for up to 6 h. We examined the distribution of ATX-70
      in the tumor in comparison with other tissues from the viewpoint of minimizing
      possible side effects of laser or ultrasound exposure while maintaining the
      treatment effect. About 24 h after administration, the tumor / plasma
      concentration ratio peaked, and relatively high tumor / skin and tumor / muscle
      concentration ratios were seen.

PMID- 11572769
TI  - Evaluation of the potential of p-boronophenylalaninol as a boron carrier in boron
      neutron capture therapy, referring to the effect on intratumor quiescent cells.
AB  - C57BL mice bearing EL4 tumors and C3H / He mice bearing SCC VII tumors received 5
      bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic
      pumps to label all proliferating (P) cells. Three hours after oral administration
      of l-p-boronophenylalanine-(10)B (BPA), or 30 min after intraperitoneal injection
      of sodium borocaptate-(10)B (BSH) or l-p-boronophenylalaninol (BPA-ol), a newly
      developed (10)B-containing alpha-amino alcohol, the tumors were irradiated with
      thermal neutron beams. For the combination with mild temperature hyperthermia
      (MTH) and / or tirapazamine (TPZ), the tumors were heated at 40 degrees C for 30
      min immediately before neutron exposure, and TPZ was intraperitoneally injected
      30 min before irradiation. The tumors were then excised, minced and trypsinized.
      The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a
      cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU
      labeling ( = quiescent (Q) cells) was determined using immunofluorescence
      staining for BrdU. Meanwhile, 6 h after irradiation, tumor cell suspensions
      obtained in the same manner were used for determining the apoptosis frequency in
      Q cells. The MN and apoptosis frequency in total (P + Q) tumor cells were
      determined from tumors that were not pretreated with BrdU. Without TPZ or MTH,
      BPA-ol increased both frequencies most markedly, especially for total cells.
      However, as with BPA, the sensitivity difference between total and Q cells was
      much larger than with BSH. On combined treatment with both MTH and TPZ, this
      sensitivity difference was markedly reduced, similarly to when BPA was used. MTH
      increased the (10)B uptake of all (10)B-compounds into both tumor cells. BPA-ol
      has good potential as a (10)B-carrier in neutron capture therapy, especially when
      combined with both MTH and TPZ.

PMID- 11572770
TI  - Whence meiosis?
AB  - Sexual reproduction predominates among eukaryotic organisms on our planet. While
      debate continues over why this should be so, burgeoning genomic and functional
      information now allows us to begin to think reasonably about some of the events
      that may have occurred to make sex possible in the first place.

PMID- 11572771
TI  - Cracking the transcriptional code for cell specification in the neural tube.
AB  - The bHLH repressor Olig2 participates in the transcriptional code governing cell
      fate specification in the ventral spinal cord. By temporally selective
      interactions with other transcription factors, Olig2 first directs motor neuron
      fate and later switches to promoting oligodendrocyte production.

PMID- 11572772
TI  - Opening of the clamp: an intimate view of an ATP-driven biological machine.
AB  - DNA polymerases require tethering to an accessory factor, typically a ring-shaped
      clamp, to remain bound to DNA during replication. Three recent structural studies
      provide unique insight into how these clamps are loaded onto DNA by the clamp
      loader machinery.

PMID- 11572773
TI  - Switching and signaling at the telomere.
AB  - This review describes the structure of telomeres, the protective DNA-protein
      complexes at eukaryotic chromosomal ends, and several molecular mechanisms
      involved in telomere functions. Also discussed are cellular responses to
      compromising the functions of telomeres and of telomerase, which synthesizes
      telomeric DNA.

PMID- 11572774
TI  - Nitrosylation. the prototypic redox-based signaling mechanism.

PMID- 11572775
TI  - Nucleosome sliding via TBP DNA binding in vivo.
AB  - Here, we show that a nucleosome obstructing transcription from the IFN-beta
      promoter slides in vivo in response to virus infection, thus exposing the
      previously masked TATA box and the initiation site, a requirement for
      transcriptional activation. Our experiments also revealed that this mode of
      chromatin remodeling is a two-step reaction. First, the enhanceosome recruits the
      SWI/SNF chromatin-remodeling complex that modifies the nucleosome to allow
      binding of TBP. Second, DNA bending is induced by TBP binding, and the nucleosome
      slides to a new position. Experiments with other DNA binding proteins
      demonstrated a strong correlation between the ability to bend DNA and nucleosome
      sliding, suggesting that the sliding is induced by the bend.

PMID- 11572776
TI  - Serial regulation of transcriptional regulators in the yeast cell cycle.
AB  - Genome-wide location analysis was used to determine how the yeast cell cycle gene
      expression program is regulated by each of the nine known cell cycle
      transcriptional activators. We found that cell cycle transcriptional activators
      that function during one stage of the cell cycle regulate transcriptional
      activators that function during the next stage. This serial regulation of
      transcriptional activators forms a connected regulatory network that is itself a
      cycle. Our results also reveal how the nine transcriptional regulators
      coordinately regulate global gene expression and diverse stage-specific functions
      to produce a continuous cycle of cellular events. This information forms the
      foundation for a complete map of the transcriptional regulatory network that
      controls the cell cycle.

PMID- 11572777
TI  - A murine model of Holt-Oram syndrome defines roles of the T-box transcription
      factor Tbx5 in cardiogenesis and disease.
AB  - Heterozygous Tbx5(del/+) mice were generated to study the mechanisms by which
      TBX5 haploinsufficiency causes cardiac and forelimb abnormalities seen in Holt
      Oram syndrome. Tbx5 deficiency in homozygous mice (Tbx5(del/del)) decreased
      expression of multiple genes and caused severe hypoplasia of posterior domains in
      the developing heart. Surprisingly, Tbx5 haploinsufficiency also markedly
      decreased atrial natriuretic factor (ANF) and connexin 40 (cx40) transcription,
      implicating these as Tbx5 target genes and providing a mechanism by which 50%
      reduction of T-box transcription factors cause disease. Direct and cooperative
      transactivation of the ANF and cx40 promoters by Tbx5 and the homeodomain
      transcription factor Nkx2-5 was also demonstrated. These studies provide one
      potential explanation for Holt-Oram syndrome conduction system defects, suggest
      mechanisms for intrafamilial phenotypic variability, and account for related
      cardiac malformations caused by other transcription factor mutations.

PMID- 11572778
TI  - A plant viral "reinitiation" factor interacts with the host translational
      machinery.
AB  - The cauliflower mosaic virus transactivator, TAV, controls translation
      reinitiation of major open reading frames on polycistronic RNA. We show here that
      TAV function depends on its association with polysomes and eukaryotic initiation
      factor eIF3 in vitro and in vivo. TAV physically interacts with eIF3 and the 60S
      ribosomal subunit. Two proteins mediating these interactions were identified:
      eIF3g and 60S ribosomal protein L24. Transient expression of eIF3g and L24 in
      plant protoplasts strongly affects TAV-mediated reinitiation activity. We
      demonstrate that TAV/eIF3/40S and eIF3/TAV/60S ternary complexes form in vitro,
      and propose that TAV mediates efficient recruitment of eIF3 to polysomes,
      allowing translation of polycistronic mRNAs by reinitiation, overcoming the
      normal cell barriers to this process.

PMID- 11572779
TI  - An E3-like factor that promotes SUMO conjugation to the yeast septins.
AB  - Covalent attachment of the ubiquitin-related protein SUMO to other proteins
      participates in many processes including signal transduction, transcriptional
      regulation, and growth control. We report the characterization of Siz1 as an E3
      like factor in the SUMO pathway. Siz1 is required for SUMO attachment to the S.
      cerevisiae septins in vivo and strongly stimulates septin sumoylation in vitro.
      Siz1 and the related protein Siz2 promote SUMO conjugation to different
      substrates at different stages of the cell cycle and, together, are required for
      most SUMO conjugation in yeast. Siz1, Siz2, and the PIAS (protein inhibitor of
      activated STAT) proteins form a conserved family defined by an unusual RING
      related motif. Our results suggest that this family functions by promoting SUMO
      conjugation to specific substrates.

PMID- 11572780
TI  - Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the
      unphosphorylated juxtamembrane region.
AB  - The Eph receptor tyrosine kinase family is regulated by autophosphorylation
      within the juxtamembrane region and the kinase activation segment. We have solved
      the X-ray crystal structure to 1.9 A resolution of an autoinhibited,
      unphosphorylated form of EphB2 comprised of the juxtamembrane region and the
      kinase domain. The structure, supported by mutagenesis data, reveals that the
      juxtamembrane segment adopts a helical conformation that distorts the small lobe
      of the kinase domain, and blocks the activation segment from attaining an
      activated conformation. Phosphorylation of conserved juxtamembrane tyrosines
      would relieve this autoinhibition by disturbing the association of the
      juxtamembrane segment with the kinase domain, while liberating phosphotyrosine
      sites for binding SH2 domains of target proteins. We propose that the
      autoinhibitory mechanism employed by EphB2 is a more general device through which
      receptor tyrosine kinases are controlled.

PMID- 11572781
TI  - Hedgehog signaling in germ cell migration.
AB  - The primitive gonad of the Drosophila embryo is formed from two cell types, the
      somatic gonad precursor cells (SGPs) and the germ cells, which originate at
      distant sites. To reach the SGPs the germ cells must undergo a complex series of
      cell movements. While there is evidence that attractive and repulsive signals
      guide germ cell migration through the embryo, the molecular identity of these
      instructive molecules has remained elusive. Here, we present evidence suggesting
      that hedgehog (hh) may serve as such an attractive guidance cue. Misexpression of
      hh in the soma induces germ cells to migrate to inappropriate locations.
      Conversely, cell-autonomous components of the hh pathway appear to be required in
      the germline for proper germ cell migration.

PMID- 11572782
TI  - An important role of neural activity-dependent CaMKIV signaling in the
      consolidation of long-term memory.
AB  - Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has been implicated in
      the regulation of CRE-dependent transcription. To investigate the role of this
      kinase in neuronal plasticity and memory, we generated transgenic mice in which
      the expression of a dominant-negative form of CaMKIV (dnCaMKIV) is restricted to
      the postnatal forebrain. In these transgenic mice, activity-induced CREB
      phosphorylation and c-Fos expression were significantly attenuated. Hippocampal
      late LTP (L-LTP) was also impaired, whereas basic synaptic function and early LTP
      (E-LTP) were unaffected. These deficits correlated with impairments in long-term
      memory, specifically in its consolidation/retention phase but not in the
      acquisition phase. These results indicate that neural activity-dependent CaMKIV
      signaling in the neuronal nucleus plays an important role in the
      consolidation/retention of hippocampus-dependent long-term memory.

PMID- 11572783
TI  - The LRR proteins capricious and Tartan mediate cell interactions during DV
      boundary formation in the Drosophila wing.
AB  - Mechanisms to segregate cell populations play important roles in tissue
      patterning during animal development. Rhombomeres and compartments in the
      ectoderm and imaginal discs of Drosophila are examples in which initially
      homogenous populations of cells come to be separated by boundaries of lineage
      restriction. Boundary formation depends in part on signaling between the
      distinctly specified cell populations that comprise compartments and in part on
      formation of affinity boundaries that prevent intermingling of these cell
      populations. Here, we present evidence that two transmembrane proteins with
      leucine-rich repeats, known as Capricious and Tartan, contribute to formation of
      the affinity boundary between dorsal and ventral compartments during Drosophila
      wing development.

PMID- 11572785
TI  - Conditional transgenic technologies.
AB  - Transgenic technology has been revolutionised by the development of techniques
      that allow temporo-spatial control of gene deletion or expression in transgenic
      animals. The ability to switch gene expression 'on' or 'off' in restricted
      tissues at specific times allows unprecedented flexibility for exploring gene
      function in both health and disease. As use of these techniques grows in all
      areas of biomedical research, an understanding of this topic is essential. In
      this review we examine the theory, application and limitations of these
      strategies, with particular reference to endocrine research.

PMID- 11572786
TI  - GH substitution reverses the growth phenotype but not the defective ossification
      in thyroid hormone receptor alpha 1-/-beta-/- mice.
AB  - Thyroid hormone receptor alpha 1, beta 1 and beta 2-deficient mice (TR alpha 1-/
      beta-/- mice) demonstrate growth retardation and defective ossification in the
      epiphyses associated with an inhibition of the GH/IGF-I axis. There are
      differences between TR alpha 1-/-beta-/- mice (receptor deficient) and the
      hypothyroid animal model (ligand deficient). Such differences include possible
      repressive actions exerted by unliganded receptors in the ligand-deficient
      (hypothyroid) model but not in the receptor-deficient model. In the present study
      we have investigated whether or not GH substitution rescues the skeletal
      phenotype of TR alpha 1-/-beta-/- mice. TR alpha 1-/-beta-/- and wild-type (WT)
      mice were treated with GH from day 18 until 10 weeks of age. GH substitution of
      mutant mice resulted in a significant and sustained stimulatory effect on the
      body weight that was not seen in WT mice. GH-treated mutant mice but not GH
      treated WT mice demonstrated increased length and periosteal circumference of the
      femur. However, GH substitution did not reverse the defective ossification seen
      in TR alpha 1-/-beta-/- mice. TR alpha 1-/-beta-/- mice displayed increased width
      of the proximal tibial growth plate, which was caused by increased width of the
      proliferative but not the hypertrophic layer. GH substitution did not restore the
      disturbed morphology of the growth plate in TR alpha 1-/-beta-/- mice. In
      summary, GH substitution reverses the growth phenotype but not the defective
      ossification in TR alpha 1-/-beta-/- mice. Our data suggest that TRs are of
      importance both for the regulation of the GH/IGF-I axis and for direct effects on
      cartilage.

PMID- 11572787
TI  - Decreased leptin uptake in hypothalamic nuclei with ageing in Wistar rats.
AB  - Leptin interacts with specific receptors in hypothalamic nuclei and modulates
      energy balance. Growing evidence has shown the association of obesity and
      hyperleptinaemia with non-insulin-dependent diabetes mellitus and insulin
      resistance. The aged Wistar rat shows peripheral insulin resistance in the
      absence of obesity and alterations of glucose homeostasis. However, it is not
      known whether, in these animals, the leptin action is altered. Here we studied
      the effect of ageing on plasma leptin concentration and the ability of
      hypothalamic nuclei to capture i.c.v.-injected digoxigenin-labelled leptin. Our
      data indicate that 24-month-old animals are hyperleptinaemic. However, daily food
      intake was greater in old animals, suggesting that they are leptin resistant.
      Leptin uptake in the hypothalamus was reduced in old rats. This uptake was a
      receptor-mediated process as demonstrated by displacement. Leptin accumulation in
      hypothalamic nuclei was partially colocalized with neuropeptide Y fibres.
      Immunohistochemical and western blot analyses showed a lower amount of the long
      form of leptin receptors in the hypothalamus of aged rats. Analysis by RT-PCR
      also demonstrated a decreased expression of leptin receptor mRNA in old animals.
      We conclude that the lower leptin uptake may be explained, at least in part, by a
      decreased amount of receptors in hypothalamic neurones of the aged rats.

PMID- 11572788
TI  - Novel expression of the stanniocalcin gene in fish.
AB  - It is currently accepted that the fish stanniocalcin (STC) gene is expressed
      exclusively in the corpuscles of Stannius (CS), unique endocrine glands on the
      kidneys of bony fishes. In this study, we have re-examined the pattern of fish
      STC gene expression in the light of the recent evidence for widespread expression
      of the gene in mammals. Surprisingly, we found by Northern blotting that the fish
      gene was also expressed in the kidneys and gonads, in addition to the CS glands.
      Moreover, Southern blotting of RT-PCR products revealed STC mRNA transcripts in
      all tissues assayed, including brain, heart, gill, muscle and intestine. In situ
      hybridization studies using digoxigenin-labeled riboprobes localized STC mRNA to
      chondrocytes, and both mature and developing nephritic tubules.
      Immunocytochemical staining indicated that the STC protein was widespread in
      cells of the gill, kidney, brain, eye, pseudobranch and skin. We also
      characterized the salmon STC gene, establishing that it was comprised of five
      exons as opposed to four in mammals. A single transcription start site was
      identified by primer extension 99 bp upstream of the start codon. This is the
      first evidence of STC gene expression in fish tissues other than the CS glands
      and suggests that, as in mammals, fish STC operates via both local and endocrine
      pathways.

PMID- 11572789
TI  - Immortalization of equine trophoblast cell lines of chorionic girdle cell lineage
      by simian virus-40 large T antigen.
AB  - Immortalized cell lines have many potential experimental applications including
      the analysis of molecular mechanisms underlying cell-specific gene expression. We
      have utilized a recombinant retrovirus encoding the simian virus-40 (SV-40) large
      T antigen to construct several immortalized cell lines of equine chorionic girdle
      cell lineage - the progenitor cells that differentiate into the equine chorionic
      gonadotropin (eCG) producing endometrial cups. Morphologically, the immortalized
      cell lines appear similar to normal chorionic girdle cells. Derivation of the
      immortalized cell lines from a chorionic girdle cell lineage was verified by
      immunological detection of cell-surface antigens specific to equine invasive
      trophoblasts. The cell lines differed, however, from mature chorionic girdle
      cells or endometrial cup cells in that they did not produce eCG and did express
      MHC class I molecules. Thus, these cell lines appear to have been arrested at a
      stage of development prior to final differentiation into endometrial cup cells.
      It was also determined that some of these cell lines as well as endometrial cups
      express the estrogen receptor-related receptor beta gene, but not the glial cell
      missing gene (GCMa) both of which are expressed in the murine and human placenta.
      Among these cell lines, three (eCG 50.5, 100.6 and 500.1) express eCG alpha mRNA.
      Since regulation of eCG alpha subunit gene is largely unknown, we investigated
      the signal transduction pathways regulating the eCG alpha subunit gene. Both
      activators of protein kinase A (PKA) and protein kinase C (PKC) induced the
      expression of eCG alpha subunit expression 3.2 (P<0.05)- and 1.9 (P<0.05)-fold
      respectively, in the eCG 500.1 cell line. However, activation of these pathways
      failed to induce eCG beta subunit expression. In conclusion, lines of equine
      trophoblast cells have been immortalized that display markers characteristic of
      those with the equine chorionic girdle and endometrial cup cell lineage. A subset
      of these cells expresses the eCG alpha subunit gene which is responsive to
      activators of the PKA and PKC signal transduction pathways.

PMID- 11572790
TI  - Activin A and activin receptors in gestational tissue from preeclamptic
      pregnancies.
AB  - Maternal serum activin A levels are elevated in women with preeclampsia. To
      explore whether this could be due, at least in part, to increased production by
      the gestational tissues, we have measured activin A in the serum of women with
      (n=23) or without preeclampsia (n=62) at 29-40 weeks of gestation and in placenta
      and fetal membranes from preterm preeclamptic (PT-PE, n=8), term preeclamptic (T
      PE, n=10) and healthy term controls (T-C, n=10). We have also explored if there
      are associated changes in activin receptor Alk2, ActRII and ActRIIB in these
      tissues. The relative amounts of receptor proteins were measured by densitometry
      on Western blots and receptors and activin beta(A) subunit localised by
      immunohistochemistry in PT-PE, T-PE and T-C gestational tissues (n=8-10/group).
      Maternal serum activin A levels were significantly elevated in women with
      preeclampsia (multiples of the normal median (MoM)=3.5, P<0.0001, Mann-Whitney U
      test) compared with healthy women (median MoM=1.0). Compared with control
      tissues, the activin A content was significantly higher in preeclamptic placentae
      (P=0.001 and P=0.0005 for PT-PE and T-PE respectively, Mann-Whitney U test), but
      significantly lower in the amnion (P=0.005 and P=0.014 for PT-PE and T-PE
      respectively) and choriodecidua (P=0.009 for T-PE). The maternal serum activin A
      level in women with preeclampsia was significantly correlated with elevated
      placental production (P=0.01, Pearson's correlation). Receptor Alk2 protein
      levels were significantly elevated in T-PE placentae (P=0.0006, Mann-Whitney U
      test), ActRIIB levels were significantly lower in PT-PE placentae (P=0.01) and
      ActRII levels were significantly lower in PT-PE choriodecidua (P=0.0002) compared
      with controls. There were no apparent differences in the distribution of the
      beta(A) subunit and receptors Alk2, ActRII and ActRIIB between control and
      preeclamptic tissues. These findings suggest that elevated levels of activin A in
      the maternal circulation in association with preeclampsia are due, at least in
      part, to increased placental production, and that the regulation of activin
      synthesis in placenta and fetal membranes is differentially regulated. Further,
      the differences in activin receptor protein levels between preeclamptic and
      control placenta and choriodecidua suggest that activin A-induced regulation may
      be altered in preeclampsia.

PMID- 11572791
TI  - Immunolocalization of estrogen receptor alpha and beta in gastric epithelium and
      enteric neurons.
AB  - A sexual dimorphism in gastric acid secretion has been known for many years, with
      women secreting less acid ( approximately 40%) than men. The mechanisms mediating
      this sex difference are unknown, but a role for estrogens is suggested from
      animal models. Two estrogen receptor (ER) subtypes, ER alpha and ER beta, mediate
      genomic effects of estrogens, and mRNA for both subtypes has been detected in the
      rat stomach. The objective of this study was to determine the cellular
      distribution of ER alpha and ER beta proteins in the rat stomach. ER alpha and ER
      beta proteins were detected in nuclei of fundic parietal cells and epithelial
      cells in the progenitor zone. In the antrum, several cells were immunoreactive
      for ER beta in regions containing stem and neuroendocrine cell types but ER alpha
      protein was not detected in antral glands. Both ER alpha and ER beta proteins
      were expressed in enteric neurons within the nucleus and cytoplasm, with specific
      punctate staining for ER alpha in cell bodies and fibers. These studies are the
      first to show differences between ER alpha and ER beta proteins in the epithelial
      cellular distribution in the fundus and antrum and to detect co-expression in
      enteric neurons. These results suggest that estrogens may inhibit gastric acid
      secretion via genomic effects in fundic parietal cells through either ER subtype
      and in antral neuroendocrine cells via ER beta. Moreover, co-expression of ER
      alpha and ER beta in enteric neurons indicates that estrogenic effects could also
      be mediated through neurogenic reflexes. Our findings imply that direct
      regulation of multiple cell types by estrogens may contribute to the modulation
      of gastric functions that have been recognized during the estrous cycle and
      between the sexes.

PMID- 11572792
TI  - Early exposure of the rat mammary gland to estrogen and progesterone blocks co
      localization of estrogen receptor expression and proliferation.
AB  - An early single full-term pregnancy induces a long-lasting protective effect
      against mammary tumor development in humans and rodents. This protective effect
      can be mimicked in rats by short-term administration of estrogen and progesterone
      hormones prior to carcinogen administration. The hormones of pregnancy are able
      to induce a proliferative block upon carcinogen challenge that is not observed in
      the age-matched virgin. We wished to determine whether carcinogen is needed to
      induce a paracrine-to-autocrine shift of proliferation in steroid receptor
      positive cells or if such a cell population already exists in the age-matched
      virgin mammary gland. Here we show that estrogen receptor positive (ER+)
      proliferating cells are rare in the developing mammary gland of the virgin rat
      but represent the majority of the proliferating cells in the mature (96-day-old)
      mammary gland of the virgin rat. As the majority of the proliferating cells
      before carcinogen challenge were ER positive, the ER+ proliferating cells in the
      mature mammary gland may represent the target cells for carcinogen-induced
      transformation. Importantly, prior exposure of the mammary gland to pregnancy
      levels of estrogen/progesterone blocked this positive association. This ability
      to block the proliferation of the ER+ cells may be one factor by which pregnancy
      induces protection against breast cancer.

PMID- 11572793
TI  - Prolactin receptor expression in the epithelia and stroma of the rat mammary
      gland.
AB  - The importance of prolactin (PRL) in regulating growth and differentiation of the
      mammary gland is well known. However, it is not well established whether PRL acts
      solely on the mammary epithelia or if it can also directly affect the mammary
      stroma. To determine where PRL could exert its effects within the mammary gland,
      we investigated the levels of expression and the localization of the PRL receptor
      (PRLR) in the epithelia and stroma of the rat mammary gland at different
      physiological stages. For these studies, we isolated parenchymal-free 'cleared'
      fat pads and intact mammary glands from virgin, 18-day-pregnant and 6-day
      lactating rats. In addition, intact mammary tissues were enzymatically digested
      to obtain epithelial cells, free of stroma. The mammary tissues, intact gland,
      stroma and isolated epithelia, were then used for immunocytochemistry, protein
      extraction and isolation of total RNA. PRLR protein was detected in tissues using
      specific polyclonal antisera (PRLR-l) by immunocytochemistry and Western blot
      analysis. Messenger RNA for PRLR was measured by ribonuclease protection assay.
      Immunocytochemistry and Western blots with the PRLR-1 antisera detected PRLR in
      wild-type rat and mouse tissues, whereas the receptor protein was absent in
      tissues from PRLR gene-deficient mice. PRLR was found to be present both in the
      epithelia and stroma of mammary glands from virgin, pregnant and lactating rats,
      as determined by immunocytochemistry and Western blotting. Western blots revealed
      the predominance of three bands migrating at 88, 90 and 92 kDa in each of the rat
      mammary samples. These represent the long form of the PRLR. During pregnancy and
      lactation, PRLR protein increased in the epithelial compartment of the mammary
      gland but did not change within the stromal compartment at any physiological
      stage examined. We also found PRLR mRNA in both the epithelia and stroma of the
      mammary gland. Again, the stroma contained lower levels of PRLR mRNA compared
      with the epithelia at all physiological stages examined. Also, the PRLR mRNA
      levels within the stroma did not change significantly during pregnancy or
      lactation, whereas PRLR mRNA within the epithelia increased twofold during
      pregnancy and fourfold during lactation when compared with virgin rats. We
      conclude from this study that PRLR is expressed both in the stromal and
      epithelial compartment of the mammary gland. This finding suggests PRL may have a
      direct affect on the mammary stroma and by that route affect mammary gland
      development.

PMID- 11572794
TI  - Angiotensin II enhances noradrenaline release from sympathetic nerves of the rat
      prostate via a novel angiotensin receptor: implications for the pathophysiology
      of benign prostatic hyperplasia.
AB  - The renin-angiotensin system (RAS) is present in the human prostate and may be
      activated in benign prostatic hyperplasia (BPH), possibly contributing to the
      pathophysiology of this disorder by enhancing local sympathetic tone and cell
      growth. The functional role of the RAS in the prostate, however, is unknown. The
      present study was undertaken to determine whether angiotensin (Ang) II enhances
      sympathetic transmission in the prostate. The neuronal stores of the rat prostate
      were labelled with [(3)H]noradrenaline (NA). Ang II and Ang I enhanced [(3)H]NA
      release in a concentration-dependent manner. The Ang II receptor subtype 1 (AT(1)
      receptor) antagonist losartan and the AT(2) receptor antagonist PD123319
      inhibited this facilitatory effect of Ang II and Ang I, whereas the other AT(2)
      receptor antagonist, CGP42112, was without effect. Bradykinin also increased
      [(3)H]NA release, which was inhibited by the B(2) receptor antagonist Hoe140. The
      angiotensin-converting enzyme inhibitor captopril inhibited the effect of Ang I,
      but potentiated that of bradykinin. Interestingly, captopril alone produced an
      increase in [(3)H]NA release which was inhibited by Hoe140. Losartan, but not
      PD123319 or CGP42112, inhibited [(125)I]-Ang II binding in Chinese hamster ovary
      cells transfected with the AT(1a) or AT(1b) receptor. In contrast, in cells
      expressing the AT(2) receptor, PD123319 and CGP42112, but not losartan, inhibited
      [(125)I]-Ang II binding. In conclusion, Ang II enhances the release of NA from
      sympathetic nerves of the rat prostate via a novel functional receptor distinct
      from the cloned AT(1a), AT(1b) or AT(2). These data provide direct evidence in
      support of a functional role for the local RAS in modulating sympathetic
      transmission in the prostate, which may have important implications for the
      pathophysiology of BPH.

PMID- 11572795
TI  - Co-administration of finasteride and the pure anti-oestrogen ICI 182,780 act
      synergistically in modulating the IGF system in rat prostate.
AB  - Prostate cancer is the most diagnosed invasive malignancy in males. Androgens and
      oestrogens have been implicated in the pathogenesis of prostate cancer. We report
      herein that the pure anti-oestrogen ICI 182,780 (ICI) reduces Ki-67 labelling
      index and IGF-I receptor levels in rat prostate. Increase of IGF-I mRNA and IGF
      binding protein 3 (IGFBP-3) accumulation occur without any effect on prostate
      weight. Finasteride significantly decreases prostate weight and inhibits IGF-I
      gene expression. IGFBP-3 mRNA, Akt and phospho-Akt are not affected by
      finasteride. Co-administration of ICI plus finasteride reduces prostate weight by
      approximately 50% and causes acinar dilation with decreased luminal epithelial
      cell thickness. The acinar epithelial cells became atrophic and inactive with
      minimal cytoplasm. We also demonstrate a synergistic effect of ICI and
      finasteride on induction of IGFBP-3 accumulation and inhibition of Akt
      phosphorylation. Because the IGF and IGFBP-3 system plays an important role in
      prostate epithelial cell proliferation, apoptosis and tumour progression, the
      inhibitory effects of finasteride and ICI on IGF system may contribute to their
      anti-proliferative activity. These observations support a potential use of ICI in
      conjunction with finasteride in the prevention and/or treatment of prostate
      cancer.

PMID- 11572796
TI  - The fourth International Standard for Human Urinary FSH and LH: specificities of
      LH seminal vesicle weight gain assays in the collaborative study differ between
      laboratories.
AB  - The fourth International Standard for Human Urinary FSH and LH (IS; in ampoules
      coded 98/704) was compared with the third International Standard for Urinary FSH
      and LH (IS 71/264) by 10 laboratories in nine countries, using FSH and LH in vivo
      bioassays. Estimates of the FSH content of the IS by augmented ovarian weight
      gain assays were homogeneous within each laboratory and over all laboratories.
      The combined weighted geometric mean estimate of FSH content of the IS (with 95%
      fiducial limits) in terms of IS 71/264 was 71.9 (69.0-74.9) IU/ampoule. Although
      estimates by seminal vesicle weight gain (SVW) assays of the relative LH
      activities of the IS and IS 71/264 were homogeneous within laboratories,
      estimates were heterogeneous between laboratories. This indicated differences
      between the spectrum of LH isoforms in the IS and IS 71/264, which were obtained
      from different manufacturers, and differences between the specificities of SVW
      assays performed in different laboratories. The differences between the
      specificities of SVW assays appeared to be related to interactions among mean
      laboratory seminal vesicle weights, age and genetic strain of rat. The finding of
      inter-laboratory differences in the specificities of SVW assays is of some
      significance, as this assay method has been generally adopted by Pharmacopoeias
      for the control of the LH content of therapeutic products. The combined
      unweighted geometric mean estimate of LH content of the IS (with 95% fiducial
      limits) in terms of IS 71/264 by SVW and ovarian ascorbate depletion assays was
      70.2 (61.7-80.0) IU/ampoule. Estimates of the FSH and LH content of ampoules of
      the IS kept at increased temperatures suggested that the IS would be adequately
      stable under normal storage conditions. On the basis of these results, the World
      Health Organization Expert Committee on Biological Standardization established
      the preparation in ampoules coded 98/704 as the fourth International Standard for
      Human Urinary FSH and LH, and assigned to the contents of each ampoule an
      activity of 72 International Units of urinary FSH and an activity of 70
      International Units of urinary LH.

PMID- 11572797
TI  - Metabolism of gonadotropins: comparisons of the primary structures of the human
      pituitary and urinary LH beta cores and the chimpanzee CG beta core demonstrate
      universality of core production.
AB  - The gonadotropins are a family of closely related heterodimeric glycoprotein
      hormones homologous in structure to disulfide-knot growth factors. Metabolic
      proteolytic processing in vivo of this disulfide cross-linked region results in
      urinary excretion of a residual highly stable core structure. The primary
      structure of the pituitary form of the hLH beta core was reported earlier, but it
      has proved difficult to isolate the urinary core, although antibodies to the
      pituitary core demonstrated its presence. By conventional and immunoaffinity
      methods, the urinary core has been isolated and its structure determined by both
      chemical and mass spectrometric methods. The urinary hLH beta core is the same as
      the pituitary-extracted hLH beta core, beta 6-40 disulfide bridged to beta 55-93,
      except that the pituitary core is more heterogeneous containing also beta 49-93.
      These findings imply a dual origin of urinary cores, both directly from a
      secreting tissue and by kidney processing of circulating hormone. We also found
      that pregnant chimpanzees excrete a CG beta core with a primary structure
      identical to that of the human CG beta core of pregnancy. In conclusion,
      gonadotropin core generation and urinary excretion of nearly identical
      gonadotropin metabolites is common among primates. Although possible biological
      functions of these core fragments remain unproven, they have diagnostic utility
      because of their stability and abundance.

PMID- 11572798
TI  - Effects of intravenous insulin-like growth factor-I and insulin administration on
      insulin-like growth factor-binding proteins in the ovine fetus.
AB  - The insulin-like growth factors (IGF) are important anabolic hormones in the
      mammalian fetus; their anabolic actions are potentially modulated by alterations
      in the IGF-binding proteins (IGFBP). We have previously shown that the
      nutritional state of the fetus affects both IGF-I and the IGFBP concentrations.
      The present study was designed to determine the effect of alterations in insulin
      and IGF-I circulating concentrations on the IGFBPs. Because both insulin and IGF
      I elicit decreases in glucose and amino acid concentrations, the concentrations
      of these substrates were clamped during the hormone infusions. Sixteen ovine
      fetuses were chronically catheterized at approximately 115 days of gestation, and
      experimental procedures performed at approximately 130 days of gestation.
      Insulin, IGF-I or both were infused for an 8-h period. Baseline concentrations of
      hormones and binding proteins were obtained, and concentrations were also
      obtained at the end of the infusion. Hepatic IGFBP-1 mRNA expression was also
      determined. Intravenous infusion of IGF-I significantly increased IGF-I
      concentrations in plasma in the ovine fetus. Intravenous infusion of insulin
      inhibited hepatic IGFBP-1 gene expression when amino acids and glucose were
      clamped. In contrast, intravenous infusion of recombinant human IGF-I (rhIGF-I)
      enhanced hepatic IGFBP-1 gene expression. Neither insulin nor rhIGF-I treatment
      had an effect on hepatic IGFBP-3 gene expression. Insulin did not alter plasma
      IGFBP-1 significantly, but it increased IGFBP-3 in plasma. rhIGF-I increased both
      IGFBP-1 and IGFBP-3 protein levels in plasma. The responses of IGFBP-1 and IGFBP
      3 to increased plasma IGF-I and insulin may serve to protect the fetus from
      exaggerated anabolic effects and to blunt the hypoglycemic potential of
      circulating IGFs and insulin.

PMID- 11572799
TI  - Differential phosphorylation of IRS-1 by insulin and insulin-like growth factor I
      receptors in Chinese hamster ovary cells.
AB  - Insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) are
      closely related receptor tyrosine kinases. Despite their high degree of homology,
      recent evidence suggests that the two receptors have distinct biological roles.
      In several recent studies, the cytoplasmic tyrosine kinase domains of the two
      receptors have been shown to possess different signalling specificities. In this
      study, we examine the hypothesis that differential phosphorylation of insulin
      receptor substrate 1 (IRS-1) may contribute to these differences in signalling
      between the two receptors. Using Chinese hamster ovary (CHO) cells stably
      expressing human IR or IGF-IR and activated by their respective ligands, we show
      that there are differences between the two receptors with regard to the
      complement of SH2-containing proteins recruited to IRS-1. In particular, IGF-IR
      appears to couple IRS-1 preferentially to Grb2 whereas, in contrast, IR appears
      to couple IRS-1 preferentially to the p85 subunit of phosphatidyl inositol 3
      kinase (PI3-kinase) and to Nck. The two receptors couple IRS-1 equally to the
      tyrosine phosphatase SHP2. We have also generated phosphospecific antibodies to
      three important tyrosine phosphorylation sites on IRS-1 (pY608, pY895 and
      pY1172). We used these antibodies to probe the phosphorylation status of these
      sites in intact CHO/IR and CHO/IGF-IR cells. In the case of pY608, these results
      also show evidence for differential phosphorylation of IRS-1 by the two
      receptors. Taken together, the results presented here support the notion that the
      cytoplasmic domains of IR and IGF-IR have differences in their intrinsic
      signalling potentials.

PMID- 11572800
TI  - Administration of bovine, porcine and equine growth hormone to the horse: effect
      on insulin-like growth factor-I and selected IGF binding proteins.
AB  - This study investigated the biochemical effects of administration of three types
      of recombinant growth hormone (GH; somatotropin) to the Thoroughbred horse.
      Equine or bovine or porcine GH was administered at a recommended dosage to 3-5
      year old Thoroughbred geldings, for up to 21 days. It was shown that, in addition
      to equine GH, bovine and porcine GH were active in the horse; however, porcine GH
      caused injection-site reactions that were so serious that administration had to
      be terminated. The concentrations of a range of GH-related serum protein markers
      were determined before, during and after the administration period. Because of
      the short half-life of GH itself, the objective was to identify GH-related
      markers that showed changes in concentration and which could be used as
      indicators of the abuse of these hormones. Among the possible markers identified,
      serum total insulin-like growth factor (IGF)-I was shown to be the most
      promising, increasing to 270% of the basal concentration for equine GH
      administration. After GH administration, IGF-I took longer to attain baseline
      concentrations than the time required for GH concentrations to recover to normal.
      The concentration obtained from the administration significantly exceeded natural
      concentrations for IGF-I, as was determined from a population of more than 2000
      Thoroughbred horses in three continents. The concentrations of serum free IGF-I
      and IGF binding protein 3 (IGFBP-3) were also shown to be significantly affected
      by equine and bovine GH.

PMID- 11572801
TI  - The metabolic effects of endotoxin are differentially affected by the pattern of
      GH administration in the rat.
AB  - GH treatment can increase the mortality and morbidity of critically ill patients.
      The mechanisms of these harmful effects of GH are unknown but have been, in part,
      ascribed to interactions between GH and the immune system. Because GH has pattern
      dependent actions we have now compared the dose-related effects of continuous and
      intermittent GH treatment given with or without an endotoxin (lipopolysaccharide;
      LPS) challenge. Male Wistar rats (n=6 per group) were treated for 5 days with
      recombinant human GH (0, 10, 100 or 1000 microg/kg per day) using either
      continuous s.c. infusion by osmotic minipump or intermittent twice daily s.c.
      injections. On day 4, endotoxin (5 mg/kg, i.p.) was injected and the animals
      monitored for a further 16 h. LPS administration alone led to neutrophilia and
      lymphopoenia, with increased plasma concentrations of urea, cholesterol,
      triglyceride, insulin and leptin, and decreased levels of IGF-I. High dose GH
      infusion (1000 microg/kg per day) followed by LPS caused greater increases in
      plasma urea, cholesterol, triglyceride, sodium and magnesium, but lower plasma
      glucose and insulin levels, than treatment with LPS alone. In contrast, twice
      daily injections of GH did not enhance these effects of endotoxin. In conclusion,
      the effects of endotoxin on plasma electrolytes, lipids, urea, glucose and
      insulin are differentially affected by the pattern of GH administration in the
      rat.

PMID- 11572802
TI  - Characterization of uptake and compartmentalization of 3,5,3'-tri-iodothyronine
      in cultured neonatal rat cardiomyocytes.
AB  - The uptake of tri-iodothyronine (T(3)) in cultured neonatal rat cardiomyocytes
      was investigated and compared with the uptake of reverse T(3 )(rT(3)) and
      thyroxine (T(4)). Cellular compartmentalization of T(3) was studied by
      distinguishing T(3) activity associated with the plasma membrane from that in the
      cytosol or incorporated in the cell nucleus. T(3) and T(4) uptake displayed
      similar temperature dependencies which, in magnitude, differed from that of rT(3)
      uptake. T(3) uptake was Na(+ )independent, and sensitive to oligomycin and
      monodansylcadaverine (42-49% and 25% inhibition of 15-min cellular uptake
      respectively). Furthermore, T(3) uptake could be inhibited by tryptophan (20%)
      and tyrosine (12%), while 2-aminobicyclo[2,2,1]heptane-carboxylic acid had no
      effect. Co-incubation with tryptophan and oligomycin resulted in an additive
      inhibition of T(3) uptake (77%). We therefore conclude that (i) T(3) uptake is
      energy dependent, (ii) receptor-mediated endocytosis may be involved and (iii)
      the aromatic amino acid transport system T may play a role, while system L is not
      involved in T(3) transport in cardiomyocytes. Co-incubation with unlabeled
      iodothyronines showed that 3,3'-di-iodothyronine and T(3) itself were the most
      effective inhibitors of T(3) uptake (30% and 36% inhibition of 15-min cellular
      uptake respectively). At 15-min incubation time, 38% of the total cell-associated
      T(3) was present in the cytosol and nucleus, and 62% remained associated to the
      plasma membrane. Unidirectional uptake rates did not saturate over a free T(3)
      concentration range up to 3.9 microM. We have concluded that T(3) uptake in
      neonatal rat cardiomyocytes occurs by an energy- and temperature-dependent
      mechanism that may include endocytosis and amino acid transport system T, and is
      not sensitive to the Na(+) gradient. Elucidation of the molecular basis for the
      T(3) transporter is the subject of current investigation.

PMID- 11572803
TI  - Thyroid function and aging: gender-related differences.
AB  - The effects of aging on human or animal thyroid function are still not well
      defined. We evaluated some aspects of thyroid function during aging using an
      animal model (young and old Dutch-Miranda rats). In old rats of both genders,
      serum thyroxine (T4) decreased but serum thyrotrophin (TSH) remained unaltered,
      suggesting a disturbance in the pituitary-thyroid feedback mechanism during
      aging. Serum tri-iodothyronine (T3) only decreased in old males, possibly because
      female rats are almost twice as efficient in hepatic T4 to T3 deiodination.
      Thyroidal T4-5'-deiodinase activity did not change much during aging, although it
      decreased slightly in males. Thyroidal iodothyronine-deiodinase type I mRNA
      expression but not total thyroidal enzymatic activity were higher in female than
      in male rats. Thus, ovarian/testicular hormones may modulate the expression
      and/or the activity of hepatic and thyroidal type I iodothyronine-deiodinase.
      Thyroperoxidase (TPO) and thyroglobulin (Tg) expression were higher in young male
      rats than in females. In males, TPO and Tg gene expression decreased with aging,
      suggesting that androgens might increase their expression. Our results showed
      that aging induces real changes in rat thyroid gland function and regulation,
      affecting at least pituitary, thyroid and liver functions. Furthermore, some of
      these changes were gender related, indicating that gonadal hormones may modulate
      thyroid gland function and regulation.

PMID- 11572804
TI  - Bimodal inhibition of connexin 43 gap junctions decreases ACTH-induced
      steroidogenesis and increases bovine adrenal cell population growth.
AB  - In order to elucidate the role of gap junctions in adrenal cell responses, we
      measured the effect of inhibiting gap junctions with 18-alpha glycerrhetinic acid
      (GA; a potent inhibitor of cell-cell communication) and connexin antisense
      transfection on cell proliferation and adrenocorticotropin (ACTH)-stimulated
      steroidogenesis. In these experiments we utilized a bovine adrenocortical cell
      (SBAC) population, which responds to ACTH treatment with a dose-dependent
      increase in steroid production, an increase in connexin 43 (alpha(1)-Cx43) gap
      junction protein concentrations, and a decrease in cell population growth. SBAC
      cell populations treated with GA had increased growth rates, decreased ACTH
      stimulated steroidogenesis, but no reduction in alpha(1)-Cx43 gap junction
      protein contents. In contrast, when SBAC cells were transfected with alpha(1)
      Cx43 antisense cDNA, gap junction protein concentration was dramatically reduced
      as expected, unlike the GA-treated cell populations. Cell populations transfected
      with alpha(1)-Cx43-antisense also exhibited increased growth rates and a
      decreased steroidogenic response to ACTH treatment as compared with control or
      vector-only transfected cell populations. The decreased responsiveness and
      increased number of cells in the population after gap junction function was
      decreased by either GA treatment or antisense transfection, suggests that gap
      junctions may be necessary factors in ACTH-stimulated responsiveness and growth
      control in the adrenal gland.

PMID- 11572806
TI  - Mastering the blood pressure numbers game.

PMID- 11572805
TI  - Quantification of prolactin receptor mRNA in multiple human tissues and cancer
      cell lines by real time RT-PCR.
AB  - Human prolactin (hPRL) has been reported to be involved in breast and prostate
      cancer development. The hPRL receptor (hPRLR) is expressed in a wide variety of
      tissues in at least three isoforms. In this study, a one-step real time reverse
      transcription PCR technique was used to determine relative expression levels of
      hPRLR mRNA in eleven human breast cancer cell lines, HeLa cells, three prostate
      cancer cell lines and nine normal human tissues. The housekeeping gene beta-actin
      was used for internal normalization. We demonstrate that hPRLR mRNA is up
      regulated in six of the eleven breast cancer cell lines tested when compared with
      normal breast tissue. Of the cancer cell lines tested, we found that T-47D cells
      have the highest level of hPRLR mRNA, followed by MDA-MB-134, BT-483, BT-474, MCF
      7 and MDA-MB-453 cells. In two breast cancer cell lines (MDA-MB-468 and BT-549),
      the hPRLR levels were found to be comparable to that of normal breast tissue.
      Three breast cancer cell lines (MDA-MB-436, MDA-MB-157 and MDA-MB-231) expressed
      hPRLR mRNA at levels lower than that of normal tissue. In contrast, in all three
      commonly used prostate cancer cell lines (LNCaP, PC-3 and DU 145), the levels of
      hPRLR mRNA were found to be down-regulated relative to that of normal prostate
      tissue. Of nine normal human tissues tested, we found that the uterus and the
      breast have the highest levels of hPRLR mRNA, followed by the kidney, the liver,
      the prostate and the ovary. The levels of hPRLR mRNA were the lowest among the
      trachea, the brain and the lung.

PMID- 11572807
TI  - Growing new heart cells.

PMID- 11572809
TI  - More data on alcohol and the heart.

PMID- 11572808
TI  - Weight-loss programs better than self-help.

PMID- 11572811
TI  - Heart lines. Revised cardiopulmonary resuscitation guidelines.

PMID- 11572810
TI  - Heart lines. Cardura update.

PMID- 11572812
TI  - Statins associated with lower dementia risk control.

PMID- 11572813
TI  - Diabetic women, regular walking, and lower cardiovascular risk.

PMID- 11572816
TI  - Ask the Doctor: I am a woman, age 48, in generally good health, although I've
      gained about 10 pounds over the past two years. My LDL cholesterol us 142 mg/dL
      and my HDL cholesterol is 58 mg/dL. I looked at the news reports on the new
      cholesterol guidelines and was extremely unhappy to see that my LDL is
      "borderline high". My doctor says I don't need drug therapy. What do you think?

PMID- 11572819
TI  - Reader mail. Raw versus cooked vegetables.

PMID- 11572820
TI  - Nutrition. Should you take a vitamin E supplement?

PMID- 11572821
TI  - Reader mail. More on sunscreen ingredients. Blood pressure readings.
      Acetaminophen clarification.

PMID- 11572822
TI  - Loss of smell: how it happens and what it means.

PMID- 11572823
TI  - Diet. Is it time to stop eating meat?

PMID- 11572824
TI  - By the way, doctor...I've heard that statins can cause cancer, at least in animal
      experiments. Is there any chance that my statin might prevent another heart
      attack in the short run, but give me cancer in the long run?

PMID- 11572825
TI  - By the way, doctor... My father-in-law has leukemia, and we all know that he's
      dying. The family is trying to solve some pretty complicated financial and legal
      problems that require his involvement, but he can't seem to focus on them.
      Leukemia's a blood disease, so I don't understand why it seems to be affecting
      his mental functions.

PMID- 11572826
TI  - The crack baby myth.

PMID- 11572827
TI  - The psychosocial treatment of schizophrenia -- Part II.

PMID- 11572828
TI  - Does violence in the media cause violent behavior?

PMID- 11572829
TI  - How schizophrenic patients die.

PMID- 11572830
TI  - Carbohydrates and health. Part I: Introducing the carbs.

PMID- 11572832
TI  - Treating exercise-induced injuries: a user's guide.

PMID- 11572831
TI  - DHEA: hope or hype?

PMID- 11572833
TI  - On call. My wife's problem with urinary leakage has improved with Kegel
      exercises. I've had dribbling since my TURP operation last month. Can these
      exercises help me, too?

PMID- 11572834
TI  - HRT vs. heart disease: down but not out.

PMID- 11572835
TI  - C-reactive protein, coronary risk, and statins.

PMID- 11572836
TI  - Shedding light on melanoma.

PMID- 11572837
TI  - Women, work, and upper extremity problems.

PMID- 11572838
TI  - By the way, doctor. I'm one year into menopause and really bothered by hot
      flashes and vaginal dryness. I'd like to take hormone replacement therapy, but
      I'm worried about increasing my risk of getting breast cancer. My doctor said I
      can take HRT at a dose longer than what's usually prescribed. What do you think?

PMID- 11572839
TI  - By the way, doctor. I recently read about a new way of screening for breast
      cancer called ductal lavage. Can you tell me anything about it?

PMID- 11572840
TI  - Self-care and health.

PMID- 11572841
TI  - Dealing with a traumatic experience immediately after it occurs.

PMID- 11572842
TI  - Cognitive and emotional reactions to traumatic events: implications for short
      term intervention.

PMID- 11572843
TI  - Early intervention--a family perspective.

PMID- 11572844
TI  - Sufficiency analysis of an integrated multicomponent approach to crisis
      intervention: Critical Incident Stress Management.

PMID- 11572845
TI  - Posttraumatic stress prevention: how do we move forward?

PMID- 11572846
TI  - Acute psychosocial preventive interventions for posttraumatic stress disorder.

PMID- 11572847
TI  - When disaster strikes--the need to be "wise before the event": crisis
      intervention with children and adolescents.

PMID- 11572849
TI  - The scientific study of unusual rapid wound healing: a case report.
AB  - This paper examines in a Western medical setting the claim made by a Middle
      Eastern school of Sufism that its members can attain unusually rapid wound
      healing from deliberately caused bodily damage. The demonstration involved a Sufi
      practitioner inserting an unsterilized metal skewer through one side of the cheek
      area of the face (lateral buccal) and out through the other side. The insertion
      was observed by Western scientists. The left facial puncture healed within 2
      minutes; the right facial puncture was three-quarters healed after 8 hours.
      According to the practitioner, the piercing was not associated with subjective
      pain. Radiological, immunological, and electroencephalograph (EEG) recordings
      were taken before and after the insertion. A random event generator (REG) was
      also run during the demonstration. Radiological and axial CT images documented
      the presence of the metal skewer through the cheeks. EEG findings were
      inconclusive. Immunological recordings showed no alterations. There was a trend
      toward REG non-randomness and, therefore, negentropy or increased complexity and
      order, which may be associated with the re-establishment of tissue integrity.
      Such rapid wound healing has therapeutic implications for new treatments of
      serious medical and pain-related problems as well as implications for the study
      of "paranormal" healing phenomena.

PMID- 11572850
TI  - Healing through the mind: extending our theories, research, and clinical
      practice.
AB  - This paper was prompted by experience with 2 kinds of experimental designs used
      to investigate the impact of psychological therapies on longevity in patients
      with metastatic cancers. The more conventional design, a randomized controlled
      trial, gave a null result, and the associated psychometric tests yielded
      essentially no useful information on qualities of patients that might favor
      healing. By contrast, the second study, using a mixed qualitative/quantitative
      analysis of data, and a basically correlative design, produced a wealth of
      information on the modes of psychological adaptation of different patients to
      their cancer, and on the relationship of many of these qualities to longer
      survival. This would seem to constitute an argument for more studies of this kind
      in research on healing. Drawing on this experience, I discuss some general
      principles for research, clinical practice, and theory building in this area,
      among them: the value of detailed, qualitative examination of subjects case by
      case; ways of applying quantitative measurements to rather ill-defined
      psychological variables; the need for intensive psychoeducational therapy
      designed to foster personal growth and change; importance of the spiritual
      component in therapy; the validity of psychological prognoses for medical
      conditions; the value of higher order constructs (for example, "involvement in
      self-help"); and conceptualization of healing as a progressive, developmental
      process, in which stages may be recognized. Some definitions and distinctions
      between different kinds of healing are also offered, in particular,
      distinguishing between spontaneous, externally-assisted, and internally-assisted
      healing, the last being what is meant by "healing through the mind."

PMID- 11572852
TI  - p53 targets chromatin structure alteration to repress alpha-fetoprotein gene
      expression.
AB  - Many of the functions ascribed to p53 tumor suppressor protein are mediated
      through transcription regulation. We have shown that p53 represses hepatic
      specific alpha-fetoprotein (AFP) gene expression by direct interaction with a
      composite HNF-3/p53 DNA binding element. Using solid-phase, chromatin-assembled
      AFP DNA templates and analysis of chromatin structure and transcription in vitro,
      we find that p53 binds DNA and alters chromatin structure at the AFP core
      promoter to regulate transcription. Chromatin assembled in the presence of
      hepatoma extracts is activated for AFP transcription with an open, accessible
      core promoter structure. Distal (-850) binding of p53 during chromatin assembly,
      but not post-assembly, reverses transcription activation concomitant with
      promoter inaccessibility to restriction enzyme digestion. Inhibition of histone
      deacetylase activity by trichostatin-A (TSA) addition, prior to and during
      chromatin assembly, activated chromatin transcription in parallel with increased
      core promoter accessibility. Chromatin immunoprecipitation analyses showed
      increased H3 and H4 acetylated histones at the core promoter in the presence of
      TSA, while histone acetylation remained unchanged at the site of distal p53
      binding. Our data reveal that p53 targets chromatin structure alteration at the
      core promoter, independently of effects on histone acetylation, to establish
      repressed AFP gene expression.

PMID- 11572854
TI  - G2 DNA damage checkpoint inhibition and antimitotic activity of 13-hydroxy-15
      oxozoapatlin.
AB  - Checkpoints activated in response to DNA damage cause arrest in the G(1) and G(2)
      phases of the cell cycle. Inhibitors of the G(2) checkpoint may be used as tools
      to study this response and also to increase the effectiveness of DNA-damaging
      therapies against cancers lacking p53 function. Using a cell-based assay for G(2)
      checkpoint inhibitors, we have screened extracts from the NCI National Institutes
      of Health Natural Products Repository and have identified 13-hydroxy-15
      oxozoapatlin (OZ) from the African tree Parinari curatellifolia. Flow cytometry
      with a mitosis-specific antibody showed that checkpoint inhibition by OZ was
      maximal at 10 microm, which released 20% of irradiated MCF-7 cells expressing
      defective p53 and 30% of irradiated HCT116p53(-/-) cells from G(2) arrest. OZ
      additively increased the response to the checkpoint inhibitors isogranulatimide
      and debromohymenialdisine, but it did not augment the effects of UCN-01 or
      caffeine. Unlike other checkpoint inhibitors, OZ did not inhibit ataxia
      telangiectasia mutated (ATM), ATM and Rad3-related (ATR), Chk1, Chk2, Plk1, or
      Ser/Thr protein phosphatases in vitro. Treatment with OZ also caused G(2)
      arrested and cycling cells to arrest in mitosis in a state resembling
      prometaphase. In these cells, the chromosomes were condensed and scattered over
      disordered mitotic spindles. The results demonstrate that OZ is both a G(2)
      checkpoint inhibitor and an antimitotic agent.

PMID- 11572853
TI  - Ethanol inhibition of N-methyl-D-aspartate receptors is reduced by site-directed
      mutagenesis of a transmembrane domain phenylalanine residue.
AB  - N-Methyl-D-aspartate (NMDA) receptors (NRs) are ionotropic receptors activated by
      glutamate and the co-agonist glycine. Ethanol inhibits NMDA receptor function,
      although its site of action is undefined. We hypothesized that ethanol acts at
      specific amino acids contained within the transmembrane (TM) domains of the
      receptor. In this study, NR1 and NR2A subunits were altered by mutagenesis and
      tested for sensitivity to ethanol. Three NR1 mutants (W636A, F817A, and L819A)
      and one NR2A mutant (F637A) failed to generate functional receptors. Pre-TM1
      (I546A, L551A, F554A, and F558A), TM1 (W563A), and TM2 (W611A) NR1 mutations did
      not affect ethanol sensitivity of heteromeric receptors. In contrast, altering a
      TM3 phenylalanine to alanine (F639A) reduced the ethanol inhibition of NMDA
      receptors expressed in oocytes and human embryonic kidney 293 cells. Mutation of
      the nearby methionine (M641) to alanine did not affect ethanol sensitivity,
      whereas changing Phe(639) to tryptophan slightly enhanced ethanol inhibition.
      NR1(F639A) did not alter the agonist potency of glutamate but did produce a
      leftward shift in the glycine concentration response for receptors containing
      NR2A and NR2B subunits. NR1(F639A) also reduced the potency of the competitive
      glycine antagonist 5,7-dichlorokynurenic acid and increased the efficacy of the
      glycine partial agonist 3-amino-1-hydroxy-2-pyrrolidinone ((+)-HA-966). These
      results suggest that ethanol may interact with amino acids contained in the TM3
      domain of NMDA subunits that are involved in transducing agonist binding to
      channel opening.

PMID- 11572855
TI  - Selective binding of collagen subtypes by integrin alpha 1I, alpha 2I, and alpha
      10I domains.
AB  - Four integrins, namely alpha(1)beta(1), alpha(2)beta(1), alpha(10)beta(1), and
      alpha(11)beta(1), form a special subclass of cell adhesion receptors. They are
      all collagen receptors, and they recognize their ligands with an inserted domain
      (I domain) in their alpha subunit. We have produced the human integrin alpha(10)I
      domain as a recombinant protein to reveal its ligand binding specificity. In
      general, alpha(10)I did recognize collagen types I-VI and laminin-1 in a Mg(2+)
      dependent manner, whereas its binding to tenascin was only slightly better than
      to albumin. When alpha(10)I was tested together with the alpha(1)I and alpha(2)I
      domains, all three I domains seemed to have their own collagen binding
      preferences. The integrin alpha(2)I domain bound much better to fibrillar
      collagens (I-III) than to basement membrane type IV collagen or to beaded
      filament-forming type VI collagen. Integrin alpha(1)I had the opposite binding
      pattern. The integrin alpha(10)I domain was similar to the alpha(1)I domain in
      that it bound very well to collagen types IV and VI. Based on the previously
      published atomic structures of the alpha(1)I and alpha(2)I domains, we modeled
      the structure of the alpha(10)I domain. The comparison of the three I domains
      revealed similarities and differences that could potentially explain their
      functional differences. Mutations were introduced into the alphaI domains, and
      their binding to types I, IV, and VI collagen was tested. In the alpha(2)I
      domain, Asp-219 is one of the amino acids previously suggested to interact
      directly with type I collagen. The corresponding amino acid in both the alpha(1)I
      and alpha(10)I domains is oppositely charged (Arg-218). The mutation D219R in the
      alpha(2)I domain changed the ligand binding pattern to resemble that of the
      alpha(1)I and alpha(10)I domains and, vice versa, the R218D mutation in the
      alpha(1)I and alpha(10)I domains created an alpha(2)I domain-like ligand binding
      pattern. Thus, all three collagen receptors appear to differ in their ability to
      recognize distinct collagen subtypes. The relatively small structural differences
      on their collagen binding surfaces may explain the functional specifics.

PMID- 11572856
TI  - Down-regulation of integrin alpha(v)beta(3) expression and integrin-mediated
      signaling in glioma cells by adenovirus-mediated transfer of antisense urokinase
      type plasminogen activator receptor (uPAR) and sense p16 genes.
AB  - Interaction between the extracellular matrix and integrin receptors on cell
      surfaces leads not only to cell adhesion but also to intracellular signaling
      events that affect cell migration, proliferation, and survival. The vitronectin
      receptor alpha(v)beta(3) integrin is of key importance in glioma cell biology.
      The expression of urokinase-type plasminogen activator receptor (uPAR) was
      recently shown to co-regulate with the expression of alpha(v)beta(3) integrin.
      Moreover, restoration of the p16 protein in glioma cells inhibits the
      alpha(v)beta(3) integrin-mediated spreading of those cells on vitronectin. Thus
      we hypothesized that adenovirus-mediated down-regulation of uPAR and
      overexpression of p16 might down-regulate the expression of alpha(v)beta(3)
      integrin and the integrin-mediated signaling in glioma cells, thereby defeating
      the malignant phenotype. In this study, we used replication-deficient adenovirus
      vectors that contain either a uPAR antisense expression cassette (Ad-uPAR) or
      wild-type p16 cDNA (Ad-p16) and a bicistronic adenovirus construct in which both
      the uPAR antisense and p16 sense expression cassettes (Ad-uPAR/p16) are inserted
      in the E1-deleted region of the vector. Infecting the malignant glioma cell line
      SNB19 with Ad-uPAR, Ad-p16, or Ad-uPAR/p16 in the presence of vitronectin
      resulted in decreased alpha(v)beta(3) integrin expression and integrin-mediated
      biological effects, including adhesion, migration, proliferation, and survival
      Our results support the therapeutic potential of simultaneously targeting uPAR
      and p16 in the treatment of gliomas.

PMID- 11572857
TI  - Human N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase cDNA is related to
      human B cell recombination activating gene-associated gene.
AB  - N-Acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) transfers
      sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 6 of N
      acetylgalactosamine 4-sulfate (GalNAc(4SO(4))) in chondroitin sulfate and
      dermatan sulfate. We have previously purified the enzyme to apparent homogeneity
      from the squid cartilage. We report here cloning and characterization of human
      GalNAc4S-6ST. The strategy for identification of human GalNAc4S-6ST consisted of:
      1) determination of the amino acid sequences of peptides derived from the
      purified squid GalNAc4S-6ST, 2) amplification of squid DNA by polymerase chain
      reaction, and 3) homology search using the amino acid sequence deduced from the
      squid DNA. The human GalNAc4S-6ST cDNA contains a single open reading frame that
      predicts a type II transmembrane protein composed of 561 amino acid residues. The
      recombinant protein expressed from the human GalNAc4S-6ST cDNA transferred
      sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 6 of the
      nonreducing terminal and internal GalNAc(4SO(4)) residues contained in
      chondroitin sulfate A and dermatan sulfate. When a trisaccharide and a
      pentasaccharide having sulfate groups at position 4 of N-acetylgalactosamine
      residues were used as acceptors, only nonreducing terminal GalNAc(4SO(4))
      residues were sulfated. The nucleotide sequence of the human GalNAc4S-6ST cDNA
      was nearly identical to the sequence of human B cell recombination activating
      gene-associated gene.

PMID- 11572858
TI  - Characterization of functional domains of the SMN protein in vivo.
AB  - The Survival of Motor Neurons (SMN) is the disease gene of spinal muscular
      atrophy. We have previously established a genetic system based on the chicken pre
      B cell line DT40, in which expression of SMN protein is regulated by
      tetracycline, to study the function of SMN in vivo. Depletion of SMN protein is
      lethal to these cells. Here we tested the functionality of mutant SMN proteins by
      determining their capacity to rescue the cells after depletion of wild-type SMN.
      Surprisingly, all of the spinal muscular atrophy-associated missense mutations
      tested were able to support cell viability and proliferation. Deletion of the
      amino acids encoded by exon 7 of the SMN gene resulted in a partial loss of
      function. A mutant SMN protein lacking both the tyrosine/glycine repeat (in exon
      6) and exon 7 failed to sustain viability, indicating that the C terminus of the
      protein is critical for SMN activity. Interestingly, the Tudor domain of SMN,
      encoded by exon 3, does not appear to be essential for SMN function since a
      mutant deleted of this domain restored cell viability. Unexpectedly, a chicken
      SMN mutant (DeltaN39) lacking the N-terminal 39 amino acids that encompass the
      Gemin2-binding domain also rescued the lethal phenotype. Moreover, the level of
      Gemin2 in DeltaN39-rescued cells was significantly reduced, indicating that
      Gemin2 is not required for DeltaN39 to perform the essential function of SMN in
      DT40 cells. These findings suggest that SMN may perform a novel function in DT40
      cells.

PMID- 11572859
TI  - Butyrate suppression of colonocyte NF-kappa B activation and cellular proteasome
      activity.
AB  - Butyrate is derived from the microbial metabolism of dietary fiber in the colon
      where it plays an important role in linking colonocyte turnover and
      differentiation to luminal content. In addition, butyrate appears to have both
      anti-inflammatory and cancer chemopreventive activities. Using confocal
      microscopy and cell fractionation studies, butyrate pretreatment of a human colon
      cell line (HT-29 cells) inhibited the tumor necrosis factor-alpha (TNF-alpha)
      induced nuclear translocation of the proinflammatory transcription factor NF
      kappaB. Butyrate inhibited NF-kappaB DNA binding within 30 min of TNF-alpha
      stimulation, consistent with an inhibition of nuclear translocation. IkappaB.NF
      kappaB complexes extracted from butyrate-treated cells were relatively resistant
      to in vitro dissociation by deoxycholate, suggesting a change in cellular IkappaB
      composition. Butyrate treatment increased p100 expression, an IkappaB that was
      not degraded upon TNF-alpha treatment. Butyrate also reduced the extent of TNF
      alpha-induced IkappaB-alpha degradation and enhanced the presence of ubiquitin
      conjugated IkappaB-alpha. The suppression of IkappaB-alpha degradation
      corresponded with a reduction in cellular proteasome activity as determined by in
      vitro proteasome assays and the increased presence of ubiquitin-conjugated
      proteins. The butyrate suppression of IkappaB-alpha degradation and proteasome
      activity may derive from its ability to inhibit histone deacetylases since the
      specific deacetylase inhibitor trichostatin A had similar effects. These results
      suggest a potential mechanism for the anti-inflammatory activity of butyrate and
      demonstrate the interplay between short chain fatty acids and cellular proteasome
      activity.

PMID- 11572861
TI  - Guanylyl cyclase/PSD-95 interaction: targeting of the nitric oxide-sensitive
      alpha2beta1 guanylyl cyclase to synaptic membranes.
AB  - The signaling molecule nitric oxide (NO) exerts most of its effects by the
      stimulation of the NO-sensitive guanylyl cyclase. Two isoforms of the NO receptor
      molecule exist: the ubiquitously occurring alpha(1)beta(1) and the
      alpha(2)beta(1) with a more limited distribution. As the isoforms are
      functionally indistinguishable, the physiological relevance of these isoforms
      remained unclear. The neuronal NO synthase has been reported to be associated
      with PSD-95. Here, we demonstrate the interaction of the so far unnoticed
      alpha(2)beta(1) isoform with PSD-95 in rat brain as shown by coprecipitation. The
      interaction is mediated by the alpha(2) C-terminal peptide and the third PDZ
      domain of PSD-95. As a consequence of the PSD-95 interaction, the so far
      considered "soluble" alpha(2)beta(1) isoform is recruited to the membrane
      fraction of synaptosomes, whereas the alpha(1)beta(1) isoform is found in the
      cytosol. Our results establish the alpha(1)beta(1) as the cytosolic and the
      alpha(2)beta(1) as the membrane-associated NO-sensitive guanylyl cyclase and
      suggest the alpha(2)beta(1) isoform as the sensor for the NO formed by the PSD-95
      associated neuronal NO synthase.

PMID- 11572860
TI  - Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell
      receptor signaling by recruitment of inhibitory molecules.
AB  - To maintain various T cell responses and immune equilibrium, activation signals
      triggered by T cell antigen receptor (TCR) must be regulated by inhibitory
      signals. Gab2, an adaptor protein of the insulin receptor substrate-1 family, has
      been shown to be involved in the downstream signaling from cytokine receptors. We
      investigated the functional role of Gab2 in TCR-mediated signal transduction.
      Gab2 was phosphorylated by ZAP-70 and co-precipitated with phosphoproteins, such
      as ZAP-70, LAT, and CD3zeta, upon TCR stimulation. Overexpression of Gab2 in
      Jurkat cells or antigen-specific T cell hybridomas resulted in the inhibition of
      NF-AT activation, interleukin-2 production, and tyrosine phosphorylation. The
      structure-function relationship of Gab2 was analyzed by mutants of Gab2. The Gab2
      mutants lacking SHP-2-binding sites mostly abrogated the inhibitory activity of
      Gab2, but its inhibitory function was restored by fusing to active SHP-2 as a
      chimeric protein. A mutant with defective phosphatidylinositol 3-kinase binding
      capacity also impaired the inhibitory activity, and the pleckstrin homology
      domain-deletion mutant revealed a crucial function of the pleckstrin homology
      domain for localization to the plasma membrane. These results suggest that Gab2
      is a substrate of ZAP-70 and functions as a switch molecule toward inhibition of
      TCR signal transduction by mediating the recruitment of inhibitory molecules to
      the TCR signaling complex.

PMID- 11572862
TI  - Brown fat UCP1 is specifically expressed in uterine longitudinal smooth muscle
      cells.
AB  - Until now, uncoupling protein 1 (UCP1) was considered as unique to brown
      adipocytes. It supports a highly regulated uncoupling of oxidative
      phosphorylation that is associated with diet as well as with non-shivering
      thermogenesis. Here we report that UCP1 is not specific to brown adipocytes and
      can be expressed in longitudinal smooth muscle layers. In the uterus, this
      conclusion was drawn from different convergent data. A specific antibody against
      mouse UCP1 revealed, in mitochondrial fractions, a protein with the same
      molecular weight as brown fat UCP1. Sensitive and specific reverse transcriptase
      polymerase chain reaction detected a mRNA whose sequence was totally homologous
      to that of brown fat UCP1 mRNA. Antibody against UCP1 as well as a UCP1 antisense
      probe specifically stained uterine longitudinal smooth muscles. UCP1 was also
      expressed in longitudinal smooth muscle of digestive and male reproductive tracts
      but was never expressed in other types of smooth muscle, including those of
      arterial vessels. In uterine tract, UCP1 content was increased after cold
      exposure or beta-adrenergic agonist treatment. It was also up-regulated during
      the postovulatory period after sexual cycle synchronization. Its content
      transiently increased during gestation and decreased markedly after birth. These
      regulations strongly argue about a role for UCP1 in thermogenesis as well as in
      relaxation of longitudinal smooth muscle layers.

PMID- 11572863
TI  - The role of protein composition in specifying nuclear inclusion formation in
      polyglutamine disease.
AB  - Intracellular inclusions are a unifying feature of polyglutamine (polyQ)
      neurodegenerative diseases, yet each polyQ disease displays a unique pattern of
      neuronal degeneration. This implies that the protein context of expanded polyQ
      plays an important role in establishing selective neurotoxicity. Here, in studies
      of the spinocerebellar ataxia type 3 disease protein ataxin-3, we demonstrate
      that the protein sequence surrounding polyQ specifies the constituents of nuclear
      inclusions (NI) formed by the disease protein. The nuclear proteins cAMP response
      element-binding protein-binding protein (CBP) and Mastermind-like-1 strongly
      colocalize only to NI formed by full-length ataxin-3, whereas the splicing factor
      SC35 colocalizes only to NI formed by a polyQ-containing, carboxyl-terminal
      fragment of ataxin-3. These differences in NI formation reflect specific protein
      interactions normally undertaken by ataxin-3, as both normal and mutant full
      length ataxin-3 co-immunoprecipitate with CBP and sediment on density gradients
      as macromolecular complexes. Moreover, normal ataxin-3 represses cAMP response
      element-binding protein-mediated transcription, indicating a functional
      consequence of ataxin-3 interactions with CBP. Finally, we show that mutant
      ataxin-3 forms insoluble intranuclear complexes, or microaggregates, before NI
      can be detected, implying a precursor-product relationship. These results suggest
      that protein context-dependent recruitment of nuclear proteins to intranuclear
      microaggregates, and subsequently to NI, may contribute to selective
      neurotoxicity in polyQ diseases.

PMID- 11572864
TI  - The stereoselective targeting of a specific enzyme-substrate complex is the
      molecular mechanism for the synergic inhibition of HIV-1 reverse transcriptase by
      (R)-(-)-PPO464: a novel generation of nonnucleoside inhibitors.
AB  - The human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse
      transcriptase (RT) inhibitor pyrrolopyridooxazepinone (PPO) derivative, (+/-)
      PPO294, was shown to be active toward wild type and mutated HIV-1 RT and to act
      synergistically in combination with 3'-azido-3'-deoxythymidine (Campiani, G.,
      Morelli, E., Fabbrini, M., Nacci, V., Greco, G., Novellino, E., Ramunno, A.,
      Maga, G., Spadari, S., Caliendo, G., Bergamini, A., Faggioli, E., Uccella, I.,
      Bolacchi, F., Marini, S., (1999) J. Med. Chem. 42, 4462-4470). The (+/-)-PPO294
      racemate was resolved into its pure enantiomers, and the absolute configuration
      was determined by x-ray analysis. Only one enantiomer, (R)-(-)-PPO464, displayed
      antiviral activity against both the wild type and the K103N mutant HIV-1 RT and
      was found to interact exclusively with the reaction intermediate formed by RT
      complexed with both the DNA and the nucleotide substrates. Being the first
      compound of its class to display this behavior, (R)-(-)-PPO464 is the
      representative of a novel generation of nonnucleoside inhibitors. (R)-(-)-PPO464
      showed significant synergism when tested in combination with other RT inhibitors
      and efficiently inhibited viral replication when tested against the laboratory
      strain HIV-1 IIIB or against either wild type or multidrug-resistant clinical
      isolates. Pharmacokinetic studies in mice and rats showed a more favorable
      profile for (R)-(-)-PPO464 than for the corresponding racemate. (R)-(-)-PPO464
      was also found to easily cross the blood-brain barrier. The coadministration of
      the HIV-1 protease inhibitor ritonavir increased the bioavailability of (R)-(-)
      PPO464, having little effect on its plasma and brain elimination rates.

PMID- 11572865
TI  - RNA editing of the human serotonin 5-HT2C receptor alters receptor-mediated
      activation of G13 protein.
AB  - The recent completion of the human genome predicted the presence of only 30,000
      genes, stressing the importance of mechanisms that increase molecular diversity
      at the post-transcriptional level. One such post-transcriptional event is RNA
      editing, which generates multiple protein isoforms from a single gene, often with
      profound functional consequences. The human serotonin 5-HT(2C) receptor undergoes
      RNA editing that creates multiple receptor isoforms. One consequence of RNA
      editing of cell surface receptors may be to alter the pattern of activation of
      heterotrimeric G-proteins and thereby shift preferred intracellular signaling
      pathways. We examined the ability of the nonedited 5-HT(2C) receptor isoform
      (INI) and two extensively edited isoforms, VSV and VGV, to interact with various
      G-protein alpha subunits. Two functional assays were utilized: the cell-based
      functional assay, Receptor Selection/Amplification Technology(TM), in which the
      pharmacological consequences of co-expression of 5HT(2C) receptor isoforms with G
      protein alpha subunits in fibroblasts were studied, and 5HT(2C) receptor-mediated
      rearrangements of the actin cytoskeleton in stable cell lines. These studies
      revealed that the nonedited 5-HT(2C) receptor functionally couples to G(q) and
      G(13). In contrast, coupling to G(13) was not detected for the extensively edited
      5-HT(2C) receptors. Thus, RNA editing represents a novel mechanism for regulating
      the pattern of activation of heterotrimeric G-proteins, molecular switches that
      control an enormous variety of biological processes.

PMID- 11572866
TI  - Interplay of clamp loader subunits in opening the beta sliding clamp of
      Escherichia coli DNA polymerase III holoenzyme.
AB  - The Escherichia coli beta dimer is a ring-shaped protein that encircles DNA and
      acts as a sliding clamp to tether the replicase, DNA polymerase III holoenzyme,
      to DNA. The gamma complex (gammadeltadelta'chipsi) clamp loader couples ATP to
      the opening and closing of beta in assembly of the ring onto DNA. These proteins
      are functionally and structurally conserved in all cells. The eukaryotic
      equivalents are the replication factor C (RFC) clamp loader and the proliferating
      cell nuclear antigen (PCNA) clamp. The delta subunit of the E. coli gamma complex
      clamp loader is known to bind beta and open it by parting one of the dimer
      interfaces. This study demonstrates that other subunits of gamma complex also
      bind beta, although weaker than delta. The gamma subunit like delta, affects the
      opening of beta, but with a lower efficiency than delta. The delta' subunit
      regulates both gamma and delta ring opening activities in a fashion that is
      modulated by ATP interaction with gamma. The implications of these actions for
      the workings of the E. coli clamp loading machinery and for eukaryotic RFC and
      PCNA are discussed.

PMID- 11572867
TI  - Identification and characterization of the DNA binding domain of CpG-binding
      protein.
AB  - CpG-binding protein is a transcriptional activator that exhibits a unique DNA
      binding specificity for unmethylated CpG motifs. CpG-binding protein contains a
      cysteine-rich CXXC domain that is conserved in DNA methyltransferase 1, methyl
      binding domain protein 1, and human trithorax. In vitro DNA binding assays reveal
      that CpG-binding protein contains a single DNA binding domain comprised of the
      CXXC domain and a short carboxyl extension. Specific mutation to alanine of
      individual conserved cysteine residues within the CXXC domain abolishes DNA
      binding activity. Denaturation/renaturation experiments in the presence of
      various metal cations demonstrate that the CXXC domain requires zinc for
      efficient DNA binding activity. Ligand selection of high affinity binding sites
      from a pool of degenerate oligonucleotides reveals that CpG-binding protein
      interacts with a variety of sequences that contains the CpG dinucleotide with a
      consensus binding site of (A/C)CpG(A/C). Mutation of the CpG motif(s) present
      within ligand-selected oligonucleotides ablates the interaction with CpG-binding
      protein, and mutation to thymine of the nucleotides flanking the CpG motifs
      reduces the affinity of CpG-binding protein. Hence, a CpG motif is necessary and
      sufficient to comprise a binding site for CpG-binding protein, although the
      immediate flanking sequence affects binding affinity.

PMID- 11572868
TI  - TFIIH inhibits CDK9 phosphorylation during human immunodeficiency virus type 1
      transcription.
AB  - Tat stimulates human immunodeficiency virus, type 1 (HIV-1), transcription
      elongation by recruitment of the human transcription elongation factor P-TEFb,
      consisting of CDK9 and cyclin T1, to the TAR RNA structure. It has been
      demonstrated further that CDK9 phosphorylation is required for high affinity
      binding of Tat/P-TEFb to the TAR RNA structure and that the state of P-TEFb
      phosphorylation may regulate Tat transactivation. We now demonstrate that CDK9
      phosphorylation is uniquely regulated in the HIV-1 preinitiation and elongation
      complexes. The presence of TFIIH in the HIV-1 preinitiation complex inhibits CDK9
      phosphorylation. As TFIIH is released from the elongation complex between +14 and
      +36, CDK9 phosphorylation is observed. In contrast to the activity in the
      "soluble" complex, phosphorylation of CDK9 is increased by the presence of Tat in
      the transcription complexes. Consistent with these observations, we have
      demonstrated that purified TFIIH directly inhibits CDK9 autophosphorylation. By
      using recombinant TFIIH subcomplexes, our results suggest that the XPB subunit of
      TFIIH is responsible for this inhibition of CDK9 phosphorylation. Interestingly,
      our results further suggest that the phosphorylated form of CDK9 is the active
      kinase for RNA polymerase II carboxyl-terminal domain phosphorylation.

PMID- 11572869
TI  - MDM2 can promote the ubiquitination, nuclear export, and degradation of p53 in
      the absence of direct binding.
AB  - MDM2 can bind the N terminus of p53 and promote its ubiquitination and export
      from the nucleus to the cytoplasm, where p53 can then be degraded by cytoplasmic
      proteasomes. Several studies have reported that an intact MDM2 binding domain is
      necessary for p53 to be targeted for ubiquitination, nuclear export, and
      degradation by MDM2. In the current study, we examined whether the MDM2 binding
      domain of p53 could be provided in trans through oligomerization between two p53
      molecules. p53 proteins mutated in their MDM2 binding domains were unable to bind
      MDM2 directly and were resistant to MDM2-mediated ubiquitination, nuclear export,
      and degradation when expressed with MDM2 alone. However, these same p53 mutants
      formed a complex with MDM2 and were efficiently ubiquitinated, exported from the
      nucleus, and degraded when co-expressed with MDM2 and wild-type p53. Moreover,
      this effect required MDM2 binding by wild-type p53 as well as oligomerization
      between wild-type p53 and the MDM2 binding-deficient p53 mutants. Taken together,
      these results support a model whereby MDM2 binding-deficient forms of p53 can
      bind MDM2 indirectly through oligomerization with wild-type p53 and are
      subsequently targeted for ubiquitination, nuclear export, and degradation. These
      findings may have important implications regarding the DNA damage response of
      p53.

PMID- 11572870
TI  - Hornerin, a novel profilaggrin-like protein and differentiation-specific marker
      isolated from mouse skin.
AB  - A novel mouse cDNA named hornerin was isolated by RNA differential display
      applied to developing mouse skin. Hornerin, which has 2,496 amino acids,
      comprises EF-hand domains at the N terminus followed by a spacer sequence and a
      large repetitive domain, indicating that hornerin is a novel member of the "fused
      gene"-type cornified envelope precursor protein family. The repetitive domain of
      hornerin was found to be rich in glycine, serine, and glutamine. Hornerin was
      expressed in the tongue, esophagus, forestomach, and skin among the adult mouse
      tissues examined, all of them cornifying stratified epithelium. In the embryonic
      mouse skin, hornerin mRNA was first detected on gestational day 15.5 in the
      epidermis coincidentally with the formation of a granular layer. In accordance
      with this, hornerin was detected in the granular and cornified layers of the
      mature epidermis. In the granular cells of the epidermis, the hornerin protein
      was detected in keratohyalin granules together with profilaggrin. Furthermore,
      Western blot analysis of the mouse skin showed that the hornerin protein was
      cleaved during the process of epidermal differentiation, indicating possible
      posttranslational proteolytic processing as is observed in profilaggrin.
      Differentiation of primary mouse epidermal keratinocytes with 0.12 mm Ca(2+)
      resulted in the induction of hornerin. These results indicate that hornerin is
      structurally as well as functionally most similar to profilaggrin among the
      family members and possibly plays pleiotropic roles, including a role in
      cornification.

PMID- 11572871
TI  - Regulation of mu-opioid receptor gene transcription by interleukin-4 and
      influence of an allelic variation within a STAT6 transcription factor binding
      site.
AB  - Morphine and the endogenous opioid peptide beta-endorphin exert neuromodulatory
      as well as immunomodulatory effects, which are transduced by mu-opioid receptors.
      In this report we show that stimulation with interleukin-4 induces mu-opioid
      receptor transcripts in human primary blood cells (T cells and polymorphonuclear
      leukocytes), immune cell lines (Raji, U-937, and HMEC-1), and dendritic cells. In
      nonstimulated immune cells this gene is silent. In addition, mu receptor
      transcription is up-regulated by interleukin-4 in cultures of primary rat
      neurons. Transient transfection experiments in Raji and SH SY5Y neuronal cells
      with human and rat reporter gene constructs linked the interleukin-4 effect
      directly to cis-active mu receptor promoter elements located at nucleotide -997
      on the human gene and nucleotide -727 on the rat gene. The interleukin-4 response
      elements function orientation independently. They bind STAT6 transcription
      factors as shown by electrophoretic mobility shift assays. In the human gene, a
      single nucleotide polymorphism within the interleukin-4 response element reduces
      the trans-activating potential of this element by 50%, which may affect the
      phenotype of persons carrying this variation. These findings provide a molecular
      basis for understanding bidirectional interactions between the opioid system and
      the immune system.

PMID- 11572872
TI  - Coordinate action of the helicase and 3' to 5' exonuclease of Werner syndrome
      protein.
AB  - Werner syndrome is a human disorder characterized by premature aging, genomic
      instability, and abnormal telomere metabolism. The Werner syndrome protein (WRN)
      is the only known member of the RecQ DNA helicase family that contains a 3' -->
      5'-exonuclease. However, it is not known whether both activities coordinate in a
      biological pathway. Here, we describe DNA structures, forked duplexes containing
      telomeric repeats, that are substrates for the simultaneous action of both WRN
      activities. We used these substrates to study the interactions between the WRN
      helicase and exonuclease on a single DNA molecule. WRN helicase unwinds at the
      forked end of the substrate, whereas the WRN exonuclease acts at the blunt end.
      Progression of the WRN exonuclease is inhibited by the action of WRN helicase
      converting duplex DNA to single strand DNA on forks of various duplex lengths.
      The WRN helicase and exonuclease act in concert to remove a DNA strand from a
      long forked duplex that is not completely unwound by the helicase. We analyzed
      the simultaneous action of WRN activities on the long forked duplex in the
      presence of the WRN protein partners, replication protein A (RPA), and the
      Ku70/80 heterodimer. RPA stimulated the WRN helicase, whereas Ku stimulated the
      WRN exonuclease. In the presence of both RPA and Ku, the WRN helicase activity
      dominated the exonuclease activity.

PMID- 11572873
TI  - Cyclobutane pyrimidine dimers are responsible for the vast majority of mutations
      induced by UVB irradiation in mammalian cells.
AB  - The most prevalent DNA lesions induced by UVB are the cyclobutane pyrimidine
      dimers (CPDs) and the pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs). It
      has been a long standing controversy as to which of these photoproduct is
      responsible for mutations in mammalian cells. Here we have introduced
      photoproduct-specific DNA photolyases into a mouse cell line carrying the
      transgenic mutation reporter genes lacI and cII. Exposure of the photolyase
      expressing cell lines to photoreactivating light resulted in almost complete
      repair of either CPDs or (6-4)PPs within less than 3 h. The mutations produced by
      the remaining, nonrepaired photoproducts were scored. The mutant frequency in the
      cII gene after photoreactivation by CPD photolyase was reduced from 127 x 10(-5)
      to 34 x 10(-5) (background, 8-10 x 10(-5)). Photoreactivation with (6-4)
      photolyase did not lower the mutant frequency appreciably. In the lacI gene the
      mutant frequency after photoreactivation repair of CPDs was reduced from 148 x
      10(-5) to 28 x 10(-5) (background, 6-10 x 10(-5)). Mutation spectra obtained with
      and without photoreactivation by CPD photolyase indicated that the remaining
      mutations were derived from background mutations, unrepaired CPDs, and other DNA
      photopoducts including perhaps a small contribution from (6-4)PPs. We conclude
      that CPDs are responsible for at least 80% of the UVB-induced mutations in this
      mammalian cell model.

PMID- 11572874
TI  - Id2 is a target of the beta-catenin/T cell factor pathway in colon carcinoma.
AB  - Activation of beta-catenin/T cell factor (TCF) transcription as a result of
      mutations in the adenomatous polyposis coli (APC) and/or beta-catenin genes
      occurs in the majority of colon tumors. An increasing number of genes, including
      c-myc and cyclin D1, have been implicated as targets of this pathway. We now
      report that the dominant negative helix-loop-helix regulator Id2 is also a target
      of the beta-catenin/TCF transcription pathway in colon adenocarcinoma.
      Investigation of the mechanism for the overexpression of Id2 in colon carcinoma
      cells demonstrated that the Id2 promoter is activated, and the Id2 protein is up
      regulated by beta-catenin. Conversely, reducing free beta-catenin blocked this
      induction of promoter activity. We have also used an electrophoretic mobility
      shift assay and supershift to identify a motif in the Id2 promoter that binds to
      TCF4 protein. Site-directed mutagenesis of this motif abolished promoter reporter
      activity. Both transfection of Id2 into SW480 cells and induction of Id2 in HT29
      colon cells was found to increase anchorage-independent survival of these cells.
      Growing evidence associates disruption to Id2 expression with tumorigenesis, and
      our findings suggest that this dysregulation of Id2 expression is due to the
      activation of the beta-catenin/TCF pathway.

PMID- 11572875
TI  - alpha-Latrotoxin, acting via two Ca2+-dependent pathways, triggers exocytosis of
      two pools of synaptic vesicles.
AB  - alpha-Latrotoxin stimulates three types of [(3)H]gamma-aminobutyric acid and
      [(14)C]glutamate release from synaptosomes. The Ca(2+)-independent component (i)
      is insensitive to SNAP-25 cleavage or depletion of vesicle contents by
      bafilomycin A1 and represents transmitter efflux mediated by alpha-latrotoxin
      pores. Two other components of release are Ca(2+)-dependent and vesicular but
      rely on distinct mechanisms. The fast receptor-mediated pathway (ii) involves
      intracellular Ca(2+) stores and acts upon sucrose-sensitive readily releasable
      vesicles; this mechanism is insensitive to inhibition of phosphatidylinositol 4
      kinase (PI 4-kinase). The delayed pore-dependent exocytotic component (iii) is
      stimulated by Ca(2+) entering through alpha-latrotoxin pores; it requires PI 4
      kinase and occurs mainly from depot vesicles. Lanthanum perturbs alpha-latrotoxin
      pores and blocks the two pore-mediated components (i, iii) but not the receptor
      mediated release (ii). alpha-Latrotoxin mutant (LTX(N4C)) cannot form pores and
      stimulates only the Ca(2+)-dependent receptor-mediated amino acid exocytosis (ii)
      (detectable biochemically and electrophysiologically). These findings explain
      experimental data obtained by different laboratories and implicate the toxin
      receptors in the regulation of the readily releasable pool of synaptic vesicles.
      Our results also suggest that, similar to noradrenergic vesicles, amino acid
      containing vesicles at some point in their cycle require PI 4-kinase.

PMID- 11572876
TI  - Lefty contributes to the remodeling of extracellular matrix by inhibition of
      connective tissue growth factor and collagen mRNA expression and increased
      proteolytic activity in a fibrosarcoma model.
AB  - Homeostasis of the extracellular matrix (ECM) of tissues is regulated by
      controlling deposition and degradation of ECM proteins. The breakdown of ECM is
      essential in blastocyst implantation and embryonic development, tissue
      morphogenesis, menstrual shedding, bone formation, tissue resorption after
      delivery, and tumor growth and invasion. TGF-beta family members are one of the
      classes of proteins that actively participate in the homeostasis of ECM. Here, we
      report on the effect of lefty, a novel member of the TGF-beta family, on the
      homeostasis of extracellular matrix in a fibrosarcoma model. Fibroblastic cells
      forced to express lefty by retroviral transduction lost their ability to deposit
      collagen in vivo. This event was associated with down-regulation of the steady
      state level of connective tissue growth factor that induces collagen type I mRNA.
      In addition, lefty transduction significantly decreased collagen type I mRNA
      expression and simultaneously increased collagenolytic, gelatinolytic,
      elastolytic, and caseinolytic activities in vivo by the transduced fibroblasts.
      These findings provide a new insight on the actions of lefty and suggest that
      this cytokine plays an active role in remodeling of the extracellular matrix in
      vivo.

PMID- 11572878
TI  - Vitamin D analogues: how do they differ and what is their clinical role?

PMID- 11572877
TI  - In vitro monomer swapping in EmrE, a multidrug transporter from Escherichia coli,
      reveals that the oligomer is the functional unit.
AB  - EmrE is a small multidrug transporter, 110 amino acids long that extrudes various
      drugs in exchange with protons, thereby rendering Escherichia coli cells
      resistant to these compounds. Negative dominance studies and radiolabeled
      substrate-binding studies suggested that EmrE functions as an oligomer.
      Projection structure of two-dimensional crystals of the protein revealed an
      asymmetric dimer. To identify the functional unit of EmrE, a novel approach was
      developed. In this method, quantitative monomer swapping is induced in detergent
      solubilized EmrE by exposure to 80 degrees C, a treatment that does not impair
      transport activity. Oligomer formation is highly specific as judged by several
      criteria, among them the fact that (35)S-EmrE can be "pulled out" from a mixture
      prepared from generally labeled cells. Using this technique, we show that
      inactive mutant subunits are functionally complemented when mixed with wild type
      subunits. The hetero-oligomers thus formed display a decreased affinity to
      substrates. In addition, sulfhydryl reagents inhibit the above hetero-oligomer
      even though Cys residues are present only in the inactive monomer. It is
      concluded that, in EmrE, the oligomer is the functional unit.

PMID- 11572879
TI  - Endothelial dysfunction and inflammation-is there a link?

PMID- 11572880
TI  - The modality of dialysis treatment: does it influence the response to
      erythropoietin treatment?

PMID- 11572881
TI  - Treatment and prevention of catheter-related infections in haemodialysis
      patients.

PMID- 11572882
TI  - Glycaemic control and graft loss following renal transplantation.

PMID- 11572883
TI  - To what extent can limiting cold ischaemia/reperfusion injury prevent delayed
      graft function?

PMID- 11572884
TI  - Impact of contaminated dialysate on long-term haemodialysis-related
      complications: is it really that important?

PMID- 11572885
TI  - Sterile filtration of dialysate: is it really of no use?

PMID- 11572886
TI  - International one-day Nephrology Update.

PMID- 11572887
TI  - Should CAPD be the first choice for dialysis in Romania? Audit of the Iasi 'C. I.
      Parhon' Dialysis Center: 1995-2000.

PMID- 11572888
TI  - Effects of the somatostatin analogue octreotide on renal function in conscious
      diabetic rats.
AB  - BACKGROUND: Studies performed during the last decade have indicated that growth
      hormone (GH) and insulin-like growth factors (IGFs) may mediate the early renal
      changes in diabetes mellitus, i.e. hypertrophy and hyperfiltration. This and
      other observations have led to the suggestion that GH/IGF inhibitors, such as
      long-acting somatostatin analogue (e.g. octreotide and lanreotide), may be useful
      in order to inhibit or prevent development of long-term diabetic complications.
      METHODS: The present study examined the acute and chronic effects of octreotide
      on renal function following induction of streptozotocin (STZ)-diabetes in rats.
      The studies were carried out in conscious, non-fasted diabetic animals. RESULTS:
      Chronic administration of octreotide for 7 days, from onset of diabetes,
      prevented the decrease of effective renal vascular resistance (ERVR), and the
      increases in filtration fraction (FF), glomerular filtration rate (GFR), and
      absolute proximal tubular fluid reabsorption (APR) induced by diabetes. The renal
      hypertrophy was only partially prevented. In the acute study, similar changes
      were observed in effective renal plasma flow (ERPF) and ERVR but FF increased and
      GFR remained unaltered. CONCLUSIONS: Chronic but not acute treatment with
      octreotide prevented the renal hyperfiltration caused by diabetes. This effect is
      most likely due to an increase in afferent arteriolar resistance.

PMID- 11572889
TI  - Identification of a new mutation in the alpha4(IV) collagen gene in a family with
      autosomal dominant Alport syndrome and hypercholesterolaemia.
AB  - BACKGROUND: Alport syndrome (AS) is a hereditary disease of the glomerular
      basement membrane in the kidney characterized by progressive renal failure,
      sensorineural deafness, and/or ocular abnormalities. In contrast to the well
      known X-linked phenotype, very little is known about the autosomal dominant form.
      Rare autosomal forms of AS have been described with mutations in COL4A3 and
      COL4A4 at chromosome region 2q35-q37, but there have been no descriptions of
      dominant forms due to a mutation in COL4A4. METHODS: We describe a Sardinian
      family with a classical AS-phenotype plus hypercholesterolaemia, a clinical
      feature also present in Fechtner syndrome (FS), a disease that segregates as an
      autosomal dominant trait. RESULTS: A suggestive linkage (LOD=2.7) between AS and
      the COL4A3/A4 locus at 2q35-q37 was identified. Other candidate collagen genes
      encoding basement membrane collagen (COL4A1/A2 and COL4A5/A6) were excluded by
      linkage analysis (13q33-q34 and Xq22), or by sequence (COL4A3). DNA sequence
      analysis of the COL4A4 gene revealed that the Lys325Asn mutation was present in
      all affected family members, but was absent in all unaffected members and in a
      random sample of the Sardinian population. A clear indication of a gene-dosage
      effect was seen in the most severely affected family member, since she carried
      the mutation in the homozygous form. CONCLUSIONS: These data confirm the
      importance of collagen 4A4 as a component in the structural integrity of the
      glomerular basement membrane and confirm the phenotypic and genetic heterogeneity
      of collagen disorders.

PMID- 11572890
TI  - Pulse cyclophosphamide therapy in frequently relapsing nephrotic syndrome.
AB  - BACKGROUND: The treatment of frequently relapsing (FR) and steroid-dependent (SD)
      idiopathic nephrotic syndrome (INS) with oral cyclophosphamide (OCP) poses
      problems of compliance, side-effects and infections. METHODS: We prospectively
      evaluated the usefulness of intravenous cyclophosphamide (IVCP) in children with
      steroid sensitive INS who were frequent relapsers or steroid dependent. Fifty-one
      children were included in the study of whom 22 were FR and 29 were SD. IVCP was
      administered in a dose of 500 mg/m(2)/month for 6 months after achieving a
      steroid-induced remission. The response to IVCP was evaluated in terms of
      remission, change in the steroid response status of the patient, duration of
      remission (i.e. proteinuria-free days), side effects and compliance with therapy.
      RESULTS: The proteinuria-free days (mean 19.9+/-3.5 before IVCP therapy vs 1256+/
      167 days after IVCP therapy) (P<0.00001), and serum albumin levels (23+/-1.6 g/l
      before IVCP therapy vs 34+/-2 g/l after IVCP therapy) (P<0.001) were
      significantly higher following IVCP therapy. The cumulative remission rate in the
      study group was 49% at 5 years and was comparable to that achieved with oral
      cyclophosphamide at a 40% lower cumulative dose. CONCLUSIONS: We conclude that
      IVCP is a safe and effective therapeutic modality in children with INS who are FR
      and SD. Its efficacy is comparable to the results obtained with oral
      cyclophosphamide based on historical comparisons with previous studies.

PMID- 11572891
TI  - The value of pulse cyclophosphamide in ANCA-associated vasculitis: meta-analysis
      and critical review.
AB  - BACKGROUND: The study aimed at studying efficacy and adverse effects of pulse
      cyclophosphamide (pCyc) treatment and to compare it to continuous
      cyclophosphamide (cCyc) for induction of remission in ANCA-associated
      vasculitides from data in the published literature. METHODS: A Medline search
      identified 14 studies, containing more than five patients. From the 11 non
      randomized studies, data on outcome following pCyc treatment were extracted.
      Results were given as fraction of the number of evaluable patients. A meta
      analysis was performed on the three prospective, randomized controlled trials to
      compare outcomes concerning remission, relapses, infection, leucopenia, death and
      renal failure in patients treated with pCyc as opposed to cCyc. RESULTS: The 11
      non-randomized studies comprised 202 patients receiving pCyc. Cyc pulses of 375
      1000 mg/sqm/pulse were applied at weekly to monthly intervals with different
      concomitant prednisolone regimens and variable adjunctive therapy. Complete
      remission was achieved in 112/191, partial remission in 23/191 evaluable
      patients. Relapses occurred in 68/135 patients, 40/115 patients were non
      responders. Leucopenia, infections, haemorrhagic cystitis, and deaths were rare.
      The meta-analysis, comprising 143 patients, showed that pCyc compared with cCyc
      treatment was significantly less likely to fail to induce remission (OR 0.29; 95%
      CI 0.12-0.73) and had a significantly lower risk of infection (OR 0.45; 95% CI
      0.23-0.89) and leucopenia (OR 0.36; 95% CI 0.17-0.78). Relapses occurred
      slightly, although not statistically significantly, more often under pCyc
      treatment (OR 1.79; 95% CI 0.85-3.75). There were no differences in end-stage
      renal failure or deaths between the two regimens. CONCLUSIONS: The currently
      available, rather sparse data show that pCyc is less toxic than cCyc therapy and
      is an at least equally potent inductor of remission, but possibly at the expense
      of a higher relapse rate. The existing data do not give sufficient information on
      outcomes as time to remission and relapse, irreversible damage or quality of life
      without which a treatment regimen cannot satisfactorily be evaluated today. A
      large prospective randomized controlled trial is needed to address these issues
      and their relative importance.

PMID- 11572892
TI  - Elevated levels of plasma von Willebrand factor and the risk of macro- and
      microvascular disease in type 2 diabetic patients with microalbuminuria.
AB  - BACKGROUND: The purpose of this study was to examine the concept suggesting that
      microalbuminuria in combination with high levels of plasma von Willebrand factor
      is a stronger predictor for cardiovascular disease and microvascular
      complications than microalbuminuria alone in type 2 diabetic patients. METHODS:
      One hundred and sixty patients with type 2 diabetes mellitus and persistent
      microalbuminuria were followed for an average of 3.8 (SD 0.3) years. 70% of the
      patients were treated with angiotensin converting enzyme (ACE)-inhibitors.
      Patients in this subanalysis were divided into two groups according to baseline
      plasma von Willebrand factor levels below or above the median. The main outcome
      was cardiovascular disease (cardiovascular mortality, non-fatal stroke, non-fatal
      myocardial infarction, coronary artery bypass graft and revascularization or
      amputation of legs), progression to diabetic nephropathy or progression in
      diabetic retinopathy. RESULTS: At baseline the two groups were comparable for
      HbA(1c), fasting levels of s-total-cholesterol, s-HDL-cholesterol and s
      triglycerides, systolic and diastolic blood pressure, gender, known diabetes
      duration, smoking habits, previous cardiovascular disease and antihypertensive
      therapy as well as retinopathy. Odds ratio for cardiovascular disease was 1.11
      (95% CI 0.45-2.73, P=0.82) (multiple logistic regression), odds ratio for
      progression to nephropathy was 1.08 (0.41-2.85, P=0.87) and odds ratio for
      progression in retinopathy was 0.96 (0.46-2.00, P=0.92), all with plasma von
      Willebrand factor levels above the median. CONCLUSIONS: Our results do not
      support the suggestion that the combination of high plasma levels of von
      Willebrand factor and microalbuminuria is a stronger predictor for cardiovascular
      disease, progression to diabetic nephropathy or progression in diabetic
      retinopathy than microalbuminuria alone in patients with type 2 diabetes and
      persistent microalbuminuria.

PMID- 11572893
TI  - Chronic peritoneal dialysis in octogenarians.
AB  - BACKGROUND: During the past few decades the pattern of end-stage renal failure
      disease has changed with increasing number of elderly patients admitted for
      dialysis. In spite of their increasing number, little is known about the optimal
      mode of therapy of the 'old old' (those >or=80 years) patients. METHODS: In this
      retrospective study, we analysed the results of treatment of 31 non
      institutionalized 'old old' patients at Toronto Western Hospital (17) and
      Scarborough General Hospital (14) and seven institutionalized patients in chronic
      care, Riverdale Hospital. The patients were on CAPD with Twin-bag Baxter (28) or
      Home Choice, Baxter or Fresenius CCPD system (10). Patients were screened at the
      CAPD clinic when routine blood investigations were done. Patient and technique
      survival, initial and final laboratory data (last visit or before death) and
      complications related/unrelated to dialysis method are presented. RESULTS:
      Multiple comorbid conditions were present at the start of the treatment and new
      added during treatment; very few were dialysis-related. The majority of non
      institutionalized patients required assistance of home-care nurse to perform
      dialysis. Peritonitis (1/28.6 patient months) and exit-site infection rate
      (1/75.1 patient months) were low and responded to treatment. Incidence of
      peritonitis was higher among institutionalized debilitated patients (1/5.3
      patient months). Incidence of hospitalization was 1/14.7 patient months and
      patients spent in hospital 7.5 days/patient year. Forty-seven per cent of
      patients survived 24 months; 39% survived 30 months. Technique survival was 91.5%
      at 12 months and 81.4% at 30 months. Poor appetite and malnutrition were frequent
      among very old patients. Patients and their families were motivated for treatment
      and discontinuation of dialysis was not higher than described elsewhere in
      literature. CONCLUSIONS: This study has demonstrated that chronic peritoneal
      dialysis could be recommended as a safe and suitable modality of treatment of end
      stage renal failure in old old patients.

PMID- 11572894
TI  - Arterial changes in paediatric haemodialysis patients undergoing renal
      transplantation.
AB  - BACKGROUND: The relationship between primary renal disease and arterial wall
      changes in paediatric haemodialysis patients has been little studied. The aim of
      the present work was to determine the influence of primary renal disease on
      arterial wall pathology in uraemic paediatric patients. METHODS: Twelve
      paediatric haemodialysis patients (seven girls, five boys) aged 11-17 years were
      included in the study. The primary renal diseases were urinary malformations in
      six patients (uropathy group) and acquired glomerular diseases (glomerulopathy
      group) in six patients. Age, sex distribution, duration of chronic renal failure,
      duration of haemodialysis, blood pressure, serum glucose, triglycerides,
      cholesterol, fibrinogen, calcium, phosphorus and parathyroid hormone levels were
      compared. Internal iliac artery samples were obtained at the time of related
      donor renal transplantation. Artery samples were fixed in formaldehyde and
      sections were stained separately with haematoxylin and eosin, Orcein, Verhoef-van
      Gieson, and Masson trichrome. RESULTS: Five arteries had fibrous or fibroelastic
      intimal thickening, medial mucoid ground substance and disruption of the internal
      elastic lamella. Two of these had microcalcification in the intimal layer;
      another two demonstrated atheromatous plaques; the remaining five were normal.
      These pathological changes were found in the arteries of all six patients with
      uropathy, whereas of the six patients with glomerulopathy only one had arterial
      changes (P<0.001). The duration of chronic renal failure was 4.8+/-1.9 years in
      the uropathy group and 2.2+/-1.2 in the glomerulopathy group (P<0.05). The two
      groups were comparable in terms of serum glucose, triglycerides, cholesterol,
      fibrinogen, calcium, and parathyroid hormone levels, presence of hypertension,
      sex distribution, and duration of haemodialysis. Plasma phosphorus and the
      calcium x phosphate product were higher in the uropathy group than in the
      glomerulopathy group (P<0.05). CONCLUSIONS: This study demonstrated that
      pathological changes are common in the arteries of uraemic paediatric patients,
      and that calcification and atherosclerosis are integral to this disease process.
      In our study, these alterations were more common in the patients with uropathy.
      We speculate that the patients with uropathy are more prone to these alterations
      due to slower progression and a longer duration of renal insufficiency.

PMID- 11572895
TI  - Evaluation, selection, and follow-up of live kidney donors: a review of current
      practice in French renal transplant centres.
AB  - BACKGROUND: A resurgence of interest in the concept of live-donor renal
      transplantation has prompted a closer look at methods of live donor evaluation,
      selection, and follow-up. The aim of this study was to describe these methods in
      all 46 French renal transplant centres. METHODS: Questionnaires were sent to all
      chief renal physicians. RESULTS: The survey was completed by 78% of centres,
      which accounted for 95% of all live-donor renal transplants carried out in France
      in 1995 and 1996. There was a substantial variation in all three steps of live
      donor management. For example, we observed variations in the screening for
      specific short- or long-term risk factors (especially cardiovascular or
      thrombotic risk factors and diabetes). In addition the exclusion criteria
      differed, especially the cut-off age for donation, which ranged from 45 to 75
      years. The composition of teams evaluating and selecting potential donors and the
      role of the potential donors in the decision-making process varied greatly among
      centres. Finally, we observed less variation in the methods of donor follow-up.
      CONCLUSIONS: The current survey revealed a marked disparity in the management of
      live donors in France. It raises the question of whether these practices should
      be codified into a set of guidelines for live-donor transplantation.

PMID- 11572896
TI  - Should Helicobacter pylori infection be treated before kidney transplantation?
AB  - BACKGROUND: Before the introduction of modern medication for ulcer disease,
      gastroduodenal complications were often fatal in recipients of kidney
      transplants. Helicobacter pylori causes gastritis and is an important risk factor
      for peptic ulcer disease and gastric malignancies. The aim of this study was to
      evaluate whether H. pylori infection influences the outcomes of kidney
      transplantation. METHODS: Between 1991 and 1994, serum H. pylori antibodies were
      determined in samples taken just before transplantation from 500 consecutive
      recipients of kidney transplants. Clinical data were collected retrospectively by
      means of questionnaires sent to the patients and from the national kidney
      transplantation registry. RESULTS: The prevalence of seropositivity of H. pylori
      was 31% in the 500 renal transplant subjects, and the seropositivity increased
      with age. There were no differences in patient or graft survival between the
      seronegative and seropositive patients. During the first 3 months after
      transplantation, five seronegative and one seropositive patient had
      gastroduodenal ulcers, with bleeding complications in three of the seronegative
      ones. After 3 months, there were more ulcers in the seropositive group (6 vs 3%)
      and more oesophagitis in the seronegative group (9 vs 7%). During the 6-year
      follow-up, two cases of gastroduodenal malignancies were found in the
      helicobacter-positive group and none in the seronegative group. CONCLUSIONS:
      Helicobacter pylori infections did not result in significant postoperative
      gastric complications. Two of the 155 seropositive patients developed
      gastroduodenal malignancies.

PMID- 11572897
TI  - Endothelial C4d deposition is associated with inferior kidney allograft outcome
      independently of cellular rejection.
AB  - BACKGROUND: Capillary deposition of complement split product C4d has been
      suggested to be a valuable marker for humoral rejection. In this retrospective
      study we evaluated the clinical impact of C4d deposition in renal allografts with
      special emphasis on associations between C4d staining patterns and histological
      features of acute rejection. METHODS: One hundred and two allograft biopsies
      obtained from 61 kidney transplants (1-532 days after transplantation; median 14
      days) were examined by immunohistochemistry on routine paraffin sections using a
      novel anti-C4d polyclonal antibody (C4dpAb). RESULTS: Fourty-two of 102 biopsies
      showed endothelial C4d deposits in peritubular capillaries (PTC).
      Histopathological analysis revealed a significantly lower frequency of positive
      C4d staining in biopsies with rather than in those without acute cellular
      rejection defined by the Banff grading schema (P<0.01). For clinical evaluation,
      patients were classified according to C4d staining in allografts (C4d(PTC)
      positive in at least one biopsy, n=31 vs C4d(PTC) negative in all biopsies,
      n=30). C4d(PTC) positive patients had significantly higher serum creatinine
      levels than C4d negative patients. Even in the absence of morphological evidence
      for rejection, differences in serum creatinine levels between C4d(PTC) positive
      and negative recipients were significant (6 months: 2.01+/-0.75 vs 1.41+/-0.27
      mg/dl; 12 months: 1.95+/-0.60 vs 1.36+/- 0.34 mg/dl; 18 months: 1.98+/-0.50 vs
      1.47+/-0.31 mg/dl; P<0.05). All patients with rejection resistant to conventional
      therapy (n=4) were in the C4d(PTC) positive subgroup. All recipients with panel
      reactive antibodies (PRA) >50% (n=8) were C4d(PTC) positive. CONCLUSIONS: Our
      data indicate that endothelial C4d deposition is associated with inferior graft
      outcome. We provide evidence that this immunohistochemical finding and its
      clinical impact are not associated with morphological signs of cellular
      rejection.

PMID- 11572898
TI  - OK432-induced killer cell activity: potential method for monitoring immunological
      complications after renal transplantation.
AB  - BACKGROUND: Various clinical and biochemical parameters are currently in use for
      monitoring allograft rejection. However, the mechanism of allograft rejection is
      complex and it is frequently difficult to obtain a prompt and accurate diagnosis.
      We examined the usefulness of OK432-induced killer cell activity as an
      immunological monitoring system for acute renal rejection after renal
      transplantation. METHODS: Twenty-four renal transplant recipients, seven patients
      on haemodialysis, and 10 normal volunteers were enrolled in our study. The killer
      cell activity of peripheral blood mononuclear cells was induced by culturing
      these cells with the immunopotentiator, OK432, a heat and penicillin-treated
      lyophilized powder of the Su-strain of Streptococcus pyogenes. RESULTS: The OK432
      induced killer cell activity of renal transplant recipients without acute
      rejection (stable recipients) was significantly lower than in normal volunteers.
      In four renal transplant recipients with acute rejection, the killer cell
      activity was significantly higher than in stable recipients. In three recipients
      suffering from opportunistic infections, killer cell activity was significantly
      suppressed compared with stable recipients. CONCLUSIONS: Our new test utilizing
      OK432-induced killer cell activity is potentially useful for monitoring the
      immunological state and complications after renal transplantation.

PMID- 11572899
TI  - Risk of heparin lock-related bleeding when using indwelling venous catheter in
      haemodialysis.
AB  - BACKGROUND: The indwelling venous catheter such as Dual-Cath or Twin-Cath is
      widely used in haemodialysis. Although the manufacturer recommends filling the
      catheter lumen with heparin after the dialysis session to prevent clotting,
      little is known about the systemic effects of such a procedure. METHODS: Twenty
      haemodialysis patients with Dual-Cath were studied. Dialysis anticoagulation was
      achieved by injecting a bolus of dalteparin. The patient/control ratio of
      activated partial thromboplastin time (aPTT) was determined at the end of the
      session immediately before and 10 min after locking with 2 ml of undiluted
      heparin (10,000 U/catheter). We also determined the catheter volume for each
      patient and measured aPTT immediately before and 10 min after heparin locking
      with this patient-specific volume. Catheter patency was followed over a 2-week
      period. RESULTS: The aPTT values determined at the end of two consecutive
      dialysis sessions were nearly normal, respectively 1.29 (+/-0.17) and 1.33 (+/
      0.22), whereas all patients had uncoagulable blood (aPTT >3.75) 10 min after
      locking with 2 ml of heparin. When catheter volumes were individually calculated,
      they were found to be substantially lower than 2.0 ml (1.21+/-0.12 for the
      arterial branch and 1.27+/-0.13 for the venous branch). aPTT was only 2.42+/-0.73
      10 min after locking with the estimated volumes except in one patient (aPTT
      >3.75). No catheter clotting was observed despite these smaller locking volumes.
      CONCLUSIONS: A risk of inducing serious bleeding does indeed exist with Dual-Cath
      heparin locking, especially in postoperative patients. This risk can be reduced
      by measuring catheter length at the time of placement in order to ensure an
      appropriate lock volume. Sodium citrate, polygeline, or urokinase are possible
      alternatives to heparin.

PMID- 11572900
TI  - A protocol of urokinase infusion and warfarin for the management of the
      thrombosed haemodialysis catheter.
AB  - BACKGROUND: Catheter dysfunction remains a significant cause of catheter loss and
      interrupted haemodialysis sessions. A number of regimens utilizing urokinase have
      been used but the optimum management of this common problem remains undetermined.
      METHODS: The study took place over 2 years and evaluated a protocol of urokinase
      infusion (25,000 U in 48 ml saline run at 4 ml/h via each limb of the catheter)
      followed by warfarin for restoration of catheter patency. RESULTS: Forty-eight
      urokinase infusions were used for 41 episodes of catheter dysfunction. Catheter
      patency was restored in 95% and only one catheter was lost. Recurrent thrombosis
      occurred in eight of 10 catheters not anticoagulated. Once anticoagulated,
      catheters worked well. Further episodes of non-function were related to a sub
      therapeutic INR. CONCLUSIONS: Our results show a high success rate for our
      protocol. We suggest an aggressive approach to the management of catheter
      thrombosis with urokinase used by infusion and carefully controlled
      anticoagulation to maintain the INR in the range 2-2.5.

PMID- 11572901
TI  - Tenckhoff catheters post-renal transplantation: the 'pull' technique?
AB  - BACKGROUND: Tenckhoff catheters are used widely for the provision of continuous
      ambulatory peritoneal dialysis. Traditionally these catheters are removed
      surgically under anaesthesia. We set out to introduce and monitor prospectively a
      technique for removal of the Tenckhoff catheter by a 'pull' technique. The
      intention was to avoid the discomfort, risk and cost of traditional surgery.
      METHODS: Over a 1-year period all renal transplant patients having their
      Tenckhoff catheter removed by this technique were monitored prospectively. All
      patients were followed for a minimum 2-year period after removal. In the pull
      technique steady non-jerky traction is applied to the catheter. Complications
      such as catheter breakage and cuff related sepsis were recorded. RESULTS: Sepsis
      related to a retained cuff occurred in only one patient early in the series.
      There were no other complications. The procedure was well tolerated. Use of local
      anaesthesia used initially, was largely phased out over the course of study and
      the procedure moved from the theatre to the ward. CONCLUSIONS: The pull technique
      is safe and well tolerated. The technique has significant advantages in selected
      patients without a history of recent peritonitis or exit site infection, in
      reducing risk to the patients, the pain of abdominal wall surgery and reduced
      usage of costly theatre time and in-patient beds.

PMID- 11572902
TI  - Conversion of Goodpasture's syndrome into membranous glomerulonephritis.

PMID- 11572903
TI  - Intraperitoneal route of magnesium sulphate supplementation in a patient with
      severe renal magnesium wasting.

PMID- 11572904
TI  - Genito-femoral nerve entrapment: a complication of stapling the ureter during
      laparoscopic live donor nephrectomy.

PMID- 11572905
TI  - Phaeochromocytoma associated with reversible renal artery stenosis.

PMID- 11572906
TI  - Ulcerating subcutaneous nodules and advanced renal failure: is it time for a new
      liver?

PMID- 11572907
TI  - Boy with 'rainbow' urine.

PMID- 11572908
TI  - Hypertension due to phaeochromocytoma--an unusual cause of multiorgan failure.

PMID- 11572909
TI  - Glomeruloid haemangioma and POEMS syndrome.

PMID- 11572911
TI  - The altruistic living donor: a commentary and two questions.

PMID- 11572912
TI  - Low dose L-arginine reduces blood pressure and endothelin-1 production in
      hypertensive uraemic rats.

PMID- 11572913
TI  - Renal thrombotic microangiopathy induced by interferon-alpha.

PMID- 11572914
TI  - Vitamin A in the treatment of renal disease.

PMID- 11572915
TI  - Gabapentin neurotoxicity in a chronic haemodialysis patient.

PMID- 11572916
TI  - Combined liver-kidney transplantation for primary hyperoxaluria type 1.

PMID- 11572917
TI  - Treatment of post-transplant lymphoproliferative disorder with rituximab and
      radiation in a patient with second renal allograft.

PMID- 11572920
TI  - Stimulus-secretion coupling and mitochondrial metabolism in steroid-secreting
      cells.
AB  - Ca(2+) signal in high-Ca(2+) perimitochondrial microdomains is amplified within
      the mitochondrial matrix and activates Ca(2+)-dependent dehydrogenases. In
      steroid-secreting cells, small cytoplasmic Ca(2+) signals may also augment
      mitochondrial Ca(2+) concentration. The ensuing formation of NADH and NADPH may
      have an essential role in supporting the increased steroid secretion.

PMID- 11572921
TI  - Unlocking mysteries of gut sensory transmission: is adenosine the key?
AB  - Endogenous adenosine acts at pre- or postsynaptic A1, A2, or A3 receptors to
      inhibit synaptic transmission in intrinsic primary afferent/AH neurons, S
      neurons, and mucosal and motility reflexes. Adenosine provides dual modulation of
      adenylyl cyclases. Its modulation of sensory transmission may be of therapeutic
      potential in gut inflammation, ischemia, and constipation.

PMID- 11572922
TI  - Born again bone: tissue engineering for bone repair.
AB  - Destruction of bone tissue due to disease and inefficient bone healing after
      traumatic injury may be addressed by tissue engineering techniques. Growth
      factor, cytokine protein, and gene therapies will be developed, which, in
      conjunction with suitable carriers, will regenerate missing bone or help in cases
      of defective healing.

PMID- 11572925
TI  - Surviving anoxia with the brain turned on.
AB  - Crucian carp is one of few vertebrates that tolerate anoxia. It maintains brain
      ATP during anoxia partially by reducing ATP consumption. However, unlike turtles,
      which become comatose during anoxia, this fish remains physically active. This
      striking difference in anoxic survival strategy is reflected all the way down to
      the cellular level.

PMID- 11572924
TI  - ATP-sensitive potassium channels in dopaminergic neurons: transducers of
      mitochondrial dysfunction.
AB  - ATP-sensitive potassium (K(ATP)) channels directly couple the metabolic state of
      a cell to its electrical activity. Dopaminergic midbrain neurons express
      alternative types of K(ATP) channels mediating their differential response to
      mitochondrial complex I inhibition. Because reduced complex I activity is present
      in Parkinson's Disease, differential K(ATP) channel expression suggests a novel
      candidate mechanism for selective dopaminergic degeneration.

PMID- 11572926
TI  - Diving beyond the limits.
AB  - Some free-ranging birds and mammals dive for periods that substantially exceed
      those for which their usable O(2) stores are estimated to last. The mechanisms
      that extend the duration of aerobic diving include marked reductions in blood
      flow (and hence O(2) delivery) to certain organs and tissues, passive gliding
      and, most probably, regional hypothermia.

PMID- 11572927
TI  - Toward a physiological understanding of human dexterity.
AB  - Dexterity, defined as the skillful manipulation of the hands, is now amenable to
      physiological investigation. Two topics are discussed here: grasping (i.e., hand
      object coupling) and bimanual coordination. Dexterity depends on powerful,
      distributed neural networks and is particularly vulnerable to brain lesions. A
      knowledge of physiological mechanisms is needed to deal with these neurological
      problems.

PMID- 11572928
TI  - Vestibular signals in self-orientation and eye movement control.
AB  - The central vestibular system receives afferent information about head position
      as well as rotation and translation. This information is used to prevent blurring
      of the retinal image but also to control self-orientation and motion in space.
      Vestibular signal processing in the brain stem appears to be linked to an
      internal model of head motion in space.

PMID- 11572929
TI  - Mechanisms of surfactant exocytosis in alveolar type II cells in vitro and in
      vivo.
AB  - Surfactant secretion must be regulated to maintain a low surface tension in the
      lung during various conditions such as exercise. In vitro studies reveal a slow,
      unique exocytotic process at the interface of stimulated and constitutive
      exocytosis. The exocytotic mechanisms and sites of regulation in vivo, however,
      are still poorly understood.

PMID- 11572930
TI  - Brain images of pain.
AB  - Combined magneto- and encephalography proves the sequential involvement of
      multiple cortical structures in pain processing. Bilateral activity in secondary
      somatosensory cortices reflects the sensory-discriminative component and is
      reduced in states of unconsciousness. Later activity in the posterior cingulum
      reflects the emotional-aversive component, which is blocked by narcoanalgesics.

PMID- 11572931
TI  - Dynamic changes in the localization of thermally unfolded nuclear proteins
      associated with chaperone-dependent protection.
AB  - Molecular chaperones are involved in the protection of cells against protein
      damage through their ability to hold, disaggregate, and refold damaged proteins
      or their ability to facilitate degradation of damaged proteins. Little is known
      about how these processes are spatially coordinated in cells. Using a heat
      sensitive nuclear model protein luciferase fused to the traceable, heat-stable
      enhanced green fluorescent protein (N-luc-EGFP), we now show that heat
      inactivation and insolubilization of luciferase were associated with accumulation
      of N-luc-EGFP at multiple foci throughout the nucleus. Coexpression of Hsp70, one
      of the major mammalian chaperones, reduced the formation of these small foci
      during heat shock. Instead, the heat-unfolded N-luc-EGFP accumulated in large,
      insoluble foci. Immunofluorescence analysis revealed that these foci colocalized
      with the nucleoli. Time-lapse analysis demonstrated that protein translocation to
      the nucleolus, in contrast to the accumulation at small foci, was fully
      reversible upon return to the normal growth temperature. This reversibility was
      associated with an increase in the level of active and soluble luciferase.
      Expression of a carboxyl-terminal deletion mutant of Hsp70(1-543), which lacked
      chaperone activity, had no effect on the localization of N-luc-EGFP, which
      suggests that the Hsp70 chaperone activity is required for the translocation
      events. Our data show that Hsp70 not only is involved in holding and refolding of
      heat-unfolded nuclear proteins but also drives them to the nucleolus during
      stress. This might prevent random aggregation of thermolabile proteins within the
      nucleus, thereby allowing their refolding at the permissive conditions and
      preventing indirect damage to other nuclear components.

PMID- 11572932
TI  - Pb(II) distributions at biofilm-metal oxide interfaces.
AB  - The distribution of aqueous Pb(II) sorbed at the interface between Burkholderia
      cepacia biofilms and hematite (alpha-Fe(2)O(3)) or corundum (alpha-Al(2)O(3))
      surfaces has been probed by using an application of the long-period x-ray
      standing wave technique. Attached bacteria and adsorbed organic matter may
      interfere with sorption processes on metal oxide surfaces by changing the
      characteristics of the electrical double layer at the solid-solution interface,
      blocking surface sites, or providing a variety of new sites for metal binding. In
      this work, Pb L(alpha) fluorescence yield profiles for samples equilibrated with
      10(-7) to 10(-3.8) M Pb(II) were measured and modeled to determine quantitatively
      the partitioning of Pb(II) at the biofilm-metal oxide interface. Our data show
      that the reactive sites on the metal oxide surfaces were not passivated by the
      formation of a monolayer biofilm. Instead, high-energy surface sites on the metal
      oxides form the dominant sink for Pb(II) at submicromolar concentrations,
      following the trend alpha-Fe(2)O(3) (0001) > alpha-Al(2)O(3) (1102) > alpha
      Al(2)O(3) (0001), despite the greater site density within the overlying biofilms.
      At [Pb] > 10(-6) M, significant Pb uptake by the biofilms was observed.

PMID- 11572933
TI  - Prudent Protomognathus and despotic Leptothorax duloticus: differential costs of
      ant slavery.
AB  - The concept of ant slavery rests on the untested assumption that slave-making
      ants impose fitness costs on colonies of the species they raid. We tested that
      assumption by comparing the summertime seasonal productivity of Leptothorax spp.
      colonies in field exclosures without slavemakers, with a colony of the obligatory
      slave-making ant Protomognathus americanus, or with a colony of the obligatory
      slavemaker Leptothorax duloticus. Leptothorax longispinosus colonies placed in
      exclosures with P. americanus colonies did not differ significantly in any
      demographic attribute from colonies in exclosures without slavemakers. By
      contrast, Leptothorax curvispinosus colonies exposed to L. duloticus experienced
      significant reductions in dealate queens, workers, and larvae relative to control
      colonies exclosed without slavemakers. The pronounced difference in the impact of
      these slavemakers on their host-species populations correlates with differences
      in the behavior of the slavemakers observed in the laboratory and likely explains
      why P. americanus is more abundant than L. duloticus in nature. It seems that
      more advanced social parasites, like anatomical parasites, evolve to minimize
      their impact on their hosts, and thus can be regarded as "prudent social
      parasites."

PMID- 11572934
TI  - Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo
      proliferative response: a CD4+ T cell regulatory mechanism.
AB  - We recently reported that the nonclassical HLA class I molecule HLA-G was
      expressed in the endomyocardial biopsies and sera of 16% of heart transplant
      patients studied. The aim of the present report is to identify cells that may be
      responsible for HLA-G protein expression during the allogeneic reaction. Carrying
      out mixed lymphocyte cultures in which the responder cell population was depleted
      either in CD4(+) or CD8(+) T cells, we found that soluble HLA-G5 protein but not
      the membrane-bound HLA-G isoform was secreted by allo-specific CD4(+) T cells
      from the responder population, which suppressed the allogeneic proliferative T
      cell response. This inhibition may be reversed by adding the anti-HLA-G 87G
      antibody to a mixed lymphocyte culture. That may indicate a previously
      uncharacterized regulatory mechanism of CD4(+) T cell proliferative response.

PMID- 11572935
TI  - SV40 replication in human mesothelial cells induces HGF/Met receptor activation:
      a model for viral-related carcinogenesis of human malignant mesothelioma.
AB  - Recent studies suggested that simian virus 40 (SV40) may cause malignant
      mesothelioma, although the pathogenic mechanism is unclear. We found that in SV40
      positive malignant mesothelioma cells, the hepatocyte growth factor (HGF)
      receptor (Met) was activated. In human mesothelial cells (HMC) transfected with
      full-length SV40 DNA (SV40-HMC), Met receptor activation was associated with S
      phase entry, acquisition of a fibroblastoid morphology, and the assembly of viral
      particles. Coculture experiments revealed the ability of SV40-HMC to infect
      permissive monkey cells (CV-1), HMC, and murine BNL CL cells. Cocultured human
      and murine SV40-positive cells expressed HGF, showed Met tyrosine phosphorylation
      and S-phase entry, and acquired a spindle-shaped morphology (spBNL), whereas CV-1
      cells were lysed. Cocultured HMC inherited from SV40-HMC the infectivity, as they
      induced lysis in cocultured CV-1 cells. Treatment with suramin or HGF-blocking
      antibodies inhibited Met tyrosine phosphorylation in all large T antigen (Tag)
      positive cells and reverted the spindle-shaped morphology of spBNL. This finding
      indicated that Met activation and subsequent biological effects were mediated by
      an autocrine HGF circuit. This, in turn, was causally related to Tag expression,
      being induced by transfection with the SV40 early region alone. Our findings
      suggest that when SV40 infects HMC it causes Met activation via an autocrine
      loop. Furthermore, SV40 replicates in HMC and infects the adjacent HMC, inducing
      an HGF-dependent Met activation and cell-cycle progression into S phase. This may
      explain how a limited number of SV40-positive cells may be sufficient to direct
      noninfected HMC toward malignant transformation.

PMID- 11572936
TI  - Microinjection and growth of bacteria in the cytosol of mammalian host cells.
AB  - Most facultative intracellular bacteria replicate in specialized phagosomes after
      being taken up by mammalian cells. Relatively few intracellular bacteria escape
      the phagosomal compartment with the help of cytolytic (pore-forming) proteins and
      replicate in the host cell cytosol. Without such toxins, intracellular bacteria
      cannot reach this cellular compartment. To circumvent the requirement of an
      "escape" step, we developed a procedure allowing the efficient direct injection
      of bacteria into the cytosol of mammalian cells. With this technique, we show
      that most bacteria, including extracellular bacteria and intracellular pathogens
      that normally reside in a vacuole, are unable to replicate in the cytosol of the
      mammalian cells. In contrast, microorganisms that replicate in the cytosol, such
      as Listeria monocytogenes, Shigella flexneri, and, to some extent, enteroinvasive
      Escherichia coli, are able to multiply in this cellular compartment after
      microinjection. Further L. monocytogenes with deletion in its PrfA-regulated hpt
      gene was found to be impaired in replication when injected into the cytosol.
      Complementation of the hpt mutation with a plasmid carrying the wild-type hpt
      gene restored the replication ability in the cytosol. These data indicate that
      cytosolic intracellular pathogens have evolved specific mechanisms to grow in
      this compartment of mammalian cells.

PMID- 11572937
TI  - 1998 SM165: a large Kuiper belt object with an irregular shape.
AB  - The recent discovery of an ancient reservoir of icy bodies at and beyond the
      orbit of Neptune-the Kuiper belt-has opened a new frontier in astronomy.
      Measurements of the physical and chemical nature of Kuiper belt objects (KBOs)
      can constrain our ideas of the processes of planet formation and evolution. Our
      1.8-m Vatican Advanced Technology Telescope and charge-coupled device camera
      observations of the KBO 1998 SM(165) indicate its brightness periodically varies
      by 0.56 magnitudes over a 4-h interval. If we assume a uniform albedo of 0.04,
      which is typical of values found in the literature for a handful of KBOs, and an
      "equator-on" aspect, we find 1998 SM(165) has axes of length 600 x 360 km. If our
      assumptions are correct, such dimensions put 1998 SM(165) among the largest
      elongated objects known in our solar system. Perhaps long ago, two nearly
      spherical KBOs of comparable size coalesced to form a compound object, or perhaps
      1998 SM(165) is the residual core of a catastrophic fragmentation of a larger
      precursor.

PMID- 11572938
TI  - "What" and "where" in the human auditory system.
AB  - The extent to which sound identification and sound localization depend on
      specialized auditory pathways was examined by using functional magnetic resonance
      imaging and event-related brain potentials. Participants performed an S1-S2 match
      to-sample task in which S1 differed from S2 in its pitch and/or location. In the
      pitch task, participants indicated whether S2 was lower, identical, or higher in
      pitch than S1. In the location task, participants were asked to localize S2
      relative to S1 (i.e., leftward, same, or rightward). Relative to location, pitch
      processing generated greater activation in auditory cortex and the inferior
      frontal gyrus. Conversely, identifying the location of S2 relative to S1
      generated greater activation in posterior temporal cortex, parietal cortex, and
      the superior frontal sulcus. Differential task-related effects on event-related
      brain potentials (ERPs) were seen in anterior and posterior brain regions
      beginning at 300 ms poststimulus and lasting for several hundred milliseconds.
      The converging evidence from two independent measurements of dissociable brain
      activity during identification and localization of identical stimuli provides
      strong support for specialized auditory streams in the human brain. These
      findings are analogous to the "what" and "where" segregation of visual
      information processing, and suggest that a similar functional organization exists
      for processing information from the auditory modality.

PMID- 11572939
TI  - Analysis of Schizosaccharomyces pombe mediator reveals a set of essential
      subunits conserved between yeast and metazoan cells.
AB  - With the identification of eight new polypeptides, we here complete the subunit
      characterization of the Schizosaccharomyces pombe RNA polymerase II holoenzyme.
      The complex contains homologs to all 10 essential gene products present in the
      Saccharomyces cerevisiae Mediator, but lacks clear homologs to any of the 10 S.
      cerevisiae components encoded by nonessential genes. S. pombe Mediator instead
      contains three unique components (Pmc2, -3, and -6), which lack homologs in other
      cell types. Presently, pmc2(+) and pmc3(+) have been shown to be nonessential
      genes. The data suggest that S. pombe and S. cerevisiae share an essential
      protein module, which associates with nonessential speciesspecific subunits. In
      support of this view, sequence analysis of the conserved yeast Mediator
      components Med4 and Med8 reveals sequence homology to the metazoan Mediator
      components Trap36 and Arc32. Therefore, 8 of 10 essential genes conserved between
      S. pombe and S. cerevisiae also have a metazoan homolog, indicating that an
      evolutionary conserved Mediator core is present in all eukaryotic cells. Our data
      suggest a closer functional relationship between yeast and metazoan Mediator than
      previously anticipated.

PMID- 11572941
TI  - Modulation of specific intestinal epithelial progenitors by enteric neurons.
AB  - The proglucagon-derived peptide glucagon-like peptide 2 (GLP-2), a product of a
      subset of gut epithelial cells, is pursued clinically for its ability to
      stimulate gut epithelial growth and repair. Here we show that although specific
      epithelial progenitors respond to GLP-2 administration, the epithelium does not
      express the GLP-2 receptor. Rather, enteric neurons express the receptor, respond
      to GLP-2, and transmit a signal (which can be blocked by the voltage-gated sodium
      channel inhibitor tetrodotoxin) back to the epithelium. Thus the nervous system
      is a key component of a feedback loop regulating epithelial growth and repair.

PMID- 11572940
TI  - Extraocular muscle is defined by a fundamentally distinct gene expression
      profile.
AB  - Skeletal muscle fibers are defined by patterned covariation of key traits that
      determine contractile and metabolic characteristics. Although the functional
      properties of most skeletal muscles result from their proportional content of a
      few conserved muscle fiber types, some, typically craniofacial, muscles exhibit
      fiber types that appear to lie outside the common phenotypic range. We analyzed
      gene expression profiles of three putative muscle classes, limb, masticatory, and
      extraocular muscle (EOM), in adult mice by high-density oligonucleotide arrays.
      Pairwise comparisons using conservative acceptance criteria identified expression
      differences in 287 genes between EOM and limb and/or masticatory muscles. Use of
      significance analysis of microarrays methodology identified up to 400 genes as
      having an EOM-specific expression pattern. Genes differentially expressed in EOM
      reflect key aspects of muscle biology, including transcriptional regulation,
      sarcomeric organization, excitation-contraction coupling, intermediary
      metabolism, and immune response. These patterned differences in gene expression
      define EOM as a distinct muscle class and may explain the unique response of
      these muscles in neuromuscular diseases.

PMID- 11572942
TI  - An expanded glutamine repeat destabilizes native ataxin-3 structure and mediates
      formation of parallel beta -fibrils.
AB  - The protein ataxin-3 contains a polyglutamine region; increasing the number of
      glutamines beyond 55 in this region gives rise to the neurodegenerative disease
      spinocerebellar ataxia type 3. This disease and other polyglutamine expansion
      diseases are characterized by large intranuclear protein aggregates (nuclear
      inclusions). By using full-length human ataxin-3, we have investigated the
      changes in secondary structure, aggregation behavior, and fibril formation
      associated with an increase from the normal length of 27 glutamines (Q27 ataxin
      3) to a pathogenic length of 78 glutamines (Q78 ataxin-3). Q78 ataxin-3
      aggregates strongly and could be purified only when expressed with a solubility
      enhancing fusion-protein partner. A marked decrease in alpha-helical secondary
      structure accompanies expansion of the polyglutamine tract, suggesting
      destabilization of the native protein. Proteolytic removal of the fusion partner
      in the Q78 protein, but not in the Q27 protein, leads to the formation of SDS
      resistant aggregates and Congo-red reactive fibrils. Infrared spectroscopy of
      fibrils reveals a high beta-sheet content and suggests a parallel, rather than an
      antiparallel, sheet conformation. We present a model for a polar zipper composed
      of parallel polyglutamine beta-sheets. Our data show that intact ataxin-3 is
      fully competent to form aggregates, and posttranslational cleavage or other
      processing is not necessary to generate a misfolding event. The data also suggest
      that the protein aggregation phenotype associated with glutamine expansion may
      derive from two effects: destabilization of the native protein structure and an
      inherent propensity for beta-fibril formation on the part of glutamine
      homopolymers.

PMID- 11572943
TI  - Strontium isotopes reveal distant sources of architectural timber in Chaco
      Canyon, New Mexico.
AB  - Between A.D. 900 and 1150, more than 200,000 conifer trees were used to build the
      prehistoric great houses of Chaco Canyon, New Mexico, in what is now a treeless
      landscape. More than one-fifth of these timbers were spruce (Picea) or fir
      (Abies) that were hand-carried from isolated mountaintops 75-100 km away. Because
      strontium from local dust, water, and underlying bedrock is incorporated by
      trees, specific logging sites can be identified by comparing (87)Sr/(86)Sr ratios
      in construction beams from different ruins and building periods to ratios in
      living trees from the surrounding mountains. (87)Sr/(86)Sr ratios show that the
      beams came from both the Chuska and San Mateo (Mount Taylor) mountains, but not
      from the San Pedro Mountains, which are equally close. Incorporation of logs from
      two sources in the same room, great house, and year suggest stockpiling and
      intercommunity collaboration at Chaco Canyon. The use of trees from both the
      Chuska and San Mateo mountains, but not from the San Pedro Mountains, as early as
      A.D. 974 suggests that selection of timber sources was driven more by regional
      socioeconomic ties than by a simple model of resource depletion with distance and
      time.

PMID- 11572944
TI  - beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits
      in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease.
AB  - Alzheimer's disease and Parkinson's disease are associated with the cerebral
      accumulation of beta-amyloid and alpha-synuclein, respectively. Some patients
      have clinical and pathological features of both diseases, raising the possibility
      of overlapping pathogenetic pathways. We generated transgenic (tg) mice with
      neuronal expression of human beta-amyloid peptides, alpha-synuclein, or both. The
      functional and morphological alterations in doubly tg mice resembled the Lewy
      body variant of Alzheimer's disease. These mice had severe deficits in learning
      and memory, developed motor deficits before alpha-synuclein singly tg mice, and
      showed prominent age-dependent degeneration of cholinergic neurons and
      presynaptic terminals. They also had more alpha-synuclein-immunoreactive neuronal
      inclusions than alpha-synuclein singly tg mice. Ultrastructurally, some of these
      inclusions were fibrillar in doubly tg mice, whereas all inclusions were
      amorphous in alpha-synuclein singly tg mice. beta-Amyloid peptides promoted
      aggregation of alpha-synuclein in a cell-free system and intraneuronal
      accumulation of alpha-synuclein in cell culture. beta-Amyloid peptides may
      contribute to the development of Lewy-body diseases by promoting the aggregation
      of alpha-synuclein and exacerbating alpha-synuclein-dependent neuronal
      pathologies. Therefore, treatments that block the production or accumulation of
      beta-amyloid peptides could benefit a broader spectrum of disorders than
      previously anticipated.

PMID- 11572945
TI  - The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D
      superfamily.
AB  - The phospholipase D (PLD) superfamily is a diverse group of proteins that
      includes enzymes involved in phospholipid metabolism, a bacterial toxin, poxvirus
      envelope proteins, and bacterial nucleases. Based on sequence comparisons, we
      show here that the tyrosyl-DNA phosphodiesterase (Tdp1) that has been implicated
      in the repair of topoisomerase I covalent complexes with DNA contains two unusual
      HKD signature motifs that place the enzyme in a distinct class within the PLD
      superfamily. Mutagenesis studies with the human enzyme in which the invariant
      histidines and lysines of the HKD motifs are changed confirm that these highly
      conserved residues are essential for Tdp1 activity. Furthermore, we show that,
      like other members of the family for which it has been examined, the reaction
      involves the formation of an intermediate in which the cleaved substrate is
      covalently linked to the enzyme. These results reveal that the hydrolytic
      reaction catalyzed by Tdp1 occurs by the phosphoryl transfer chemistry that is
      common to all members of the PLD superfamily.

PMID- 11572946
TI  - Neuronal representations of stimulus associations develop in the temporal lobe
      during learning.
AB  - Visual stimuli that are frequently seen together become associated in long-term
      memory, such that the sight of one stimulus readily brings to mind the thought or
      image of the other. It has been hypothesized that acquisition of such long-term
      associative memories proceeds via the strengthening of connections between
      neurons representing the associated stimuli, such that a neuron initially
      responding only to one stimulus of an associated pair eventually comes to respond
      to both. Consistent with this hypothesis, studies have demonstrated that
      individual neurons in the primate inferior temporal cortex tend to exhibit
      similar responses to pairs of visual stimuli that have become behaviorally
      associated. In the present study, we investigated the role of these areas in the
      formation of conditional visual associations by monitoring the responses of
      individual neurons during the learning of new stimulus pairs. We found that many
      neurons in both area TE and perirhinal cortex came to elicit more similar
      neuronal responses to paired stimuli as learning proceeded. Moreover, these
      neuronal response changes were learning-dependent and proceeded with an average
      time course that paralleled learning. This experience-dependent plasticity of
      sensory representations in the cerebral cortex may underlie the learning of
      associations between objects.

PMID- 11572947
TI  - Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the
      KCNQ2 K+ channel.
AB  - KCNQ2 and KCNQ3 are two homologous K(+) channel subunits that can combine to form
      heterotetrameric channels with properties of neuronal M channels. Loss-of
      function mutations in either subunit can lead to benign familial neonatal
      convulsions (BFNC), a generalized, idiopathic epilepsy of the newborn. We now
      describe a syndrome in which BFNC is followed later in life by myokymia,
      involuntary contractions of skeletal muscles. All affected members of the
      myokymia/BFNC family carried a mutation (R207W) that neutralized a charged amino
      acid in the S4 voltage-sensor segment of KCNQ2. This substitution led to a shift
      of voltage-dependent activation of KCNQ2 and a dramatic slowing of activation
      upon depolarization. Myokymia is thought to result from hyperexcitability of the
      lower motoneuron, and indeed both KCNQ2 and KCNQ3 mRNAs were detected in the
      anterior horn of the spinal cord where the cells of the lower motoneurons arise.
      We propose that a difference in firing patterns between motoneurons and central
      neurons, combined with the drastically slowed voltage activation of the R207W
      mutant, explains why this particular KCNQ2 mutant causes myokymia in addition to
      BFNC.

PMID- 11572948
TI  - Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing
      the ability of producing secondary metabolites.
AB  - Streptomyces avermitilis is a soil bacterium that carries out not only a complex
      morphological differentiation but also the production of secondary metabolites,
      one of which, avermectin, is commercially important in human and veterinary
      medicine. The major interest in this genus Streptomyces is the diversity of its
      production of secondary metabolites as an industrial microorganism. A major
      factor in its prominence as a producer of the variety of secondary metabolites is
      its possession of several metabolic pathways for biosynthesis. Here we report
      sequence analysis of S. avermitilis, covering 99% of its genome. At least 8.7
      million base pairs exist in the linear chromosome; this is the largest bacterial
      genome sequence, and it provides insights into the intrinsic diversity of the
      production of the secondary metabolites of Streptomyces. Twenty-five kinds of
      secondary metabolite gene clusters were found in the genome of S. avermitilis.
      Four of them are concerned with the biosyntheses of melanin pigments, in which
      two clusters encode tyrosinase and its cofactor, another two encode an ochronotic
      pigment derived from homogentiginic acid, and another polyketide-derived melanin.
      The gene clusters for carotenoid and siderophore biosyntheses are composed of
      seven and five genes, respectively. There are eight kinds of gene clusters for
      type-I polyketide compound biosyntheses, and two clusters are involved in the
      biosyntheses of type-II polyketide-derived compounds. Furthermore, a polyketide
      synthase that resembles phloroglucinol synthase was detected. Eight clusters are
      involved in the biosyntheses of peptide compounds that are synthesized by
      nonribosomal peptide synthetases. These secondary metabolite clusters are widely
      located in the genome but half of them are near both ends of the genome. The
      total length of these clusters occupies about 6.4% of the genome.

PMID- 11572949
TI  - Retrieval of memory for fear-motivated training initiates extinction requiring
      protein synthesis in the rat hippocampus.
AB  - Evidence that protein synthesis inhibitors induce amnesia in a variety of species
      and learning paradigms indicates that the consolidation of newly acquired
      information into stable memories requires the synthesis of new proteins. Because
      extinction of a response also requires acquisition of new information,
      extinction, like original learning, would be expected to require protein
      synthesis. The present experiments examined the involvement of protein synthesis
      in the hippocampus in the extinction of a learned fear-based response known to
      involve the hippocampus. Rats were trained in a one-trial inhibitory avoidance
      task in which they received footshock after stepping from a small platform to a
      grid floor. They were then given daily retention tests without footshock. The
      inhibitory response (e.g., remaining on the platform) gradually extinguished with
      repeated testing over several days. Footshock administered in a different
      context, instead of a retention test, prevented the extinction. Infusions of the
      protein synthesis inhibitor anisomycin (80 microg) into the CA1 region of the
      hippocampus (bilaterally) 10 min before inhibitory avoidance training impaired
      retention on all subsequent tests. Anisomycin infused into the hippocampus
      immediately after the 1st retention test blocked extinction of the response.
      Infusions administered before the 1st retention test induced a temporary (i.e., 1
      day) reduction in retention performance and blocked subsequent extinction. These
      findings are consistent with other evidence that anisomycin blocks both the
      consolidation of original learning and extinction.

PMID- 11572951
TI  - Early membrane estrogenic effects required for full expression of slower genomic
      actions in a nerve cell line.
AB  - Interpretations of steroid hormone actions as slow, nuclear, transcriptional
      events have frequently been seen as competing against inferences of rapid
      membrane actions. We have discovered conditions where membrane-limited effects
      potentiate later transcriptional actions in a nerve cell line. Making use of a
      two-pulse hormonal schedule in a transfection system, early and brief
      administration of conjugated, membrane-limited estradiol was necessary but not
      sufficient for full transcriptional potency of the second estrogen pulse.
      Efficacy of the first pulse depended on intact signal transduction pathways.
      Surprisingly, the actions of both pulses were blocked by a classical estrogen
      receptor (ER) antagonist. Thus, two different modes of steroid hormone action can
      synergize.

PMID- 11572952
TI  - An evolutionary approach to ecosystem functioning.

PMID- 11572953
TI  - Unlocking the mysteries of leaf primordia formation.

PMID- 11572954
TI  - AKT plays a central role in tumorigenesis.

PMID- 11572955
TI  - How can we prevent cancer?

PMID- 11572956
TI  - A radical approach to stroke therapy.

PMID- 11572957
TI  - Replacing iterative algorithms with single-pass algorithms.

PMID- 11572958
TI  - Arthur M. Sackler and science.

PMID- 11572959
TI  - Neural roles for heme oxygenase: contrasts to nitric oxide synthase.
AB  - The heme oxygenase (HO) and nitric oxide (NO) synthase (NOS) systems display
      notable similarities as well as differences. HO and NOS are both oxidative
      enzymes using NADPH as an electron donor. The constitutive forms of the enzyme
      are differentially activated, with calcium entry stimulating NOS by binding to
      calmodulin, whereas calcium entry activates protein kinase C to phosphorylate and
      activate HO2. Although both NO and carbon monoxide (CO) stimulate soluble
      guanylyl cyclase to form cGMP, NO also S-nitrosylates selected protein targets.
      Both involve constitutive and inducible biosynthetic enzymes. However, functions
      of the inducible forms are virtual opposites. Macrophage-inducible NOS generates
      NO to kill other cells, whereas HO1 generates bilirubin to exert antioxidant
      cytoprotective effects and also provides cytoprotection by facilitating iron
      extrusion from cells. The neuronal form of HO, HO2, is also cytoprotective.
      Normally, neural NO in the brain seems to exert some sort of behavioral
      inhibition. However, excess release of NO in response to glutamate's N-methyl-d
      aspartate receptor activation leads to stroke damage. On the other hand, massive
      neuronal firing during a stroke presumably activates HO2, leading to
      neuroprotective actions of bilirubin. Loss of this neuroprotection after HO
      inhibition by mutant forms of amyloid precursor protein may mediate neurotoxicity
      in Familial Alzheimer's Disease. NO and CO both appear to be neurotransmitters in
      the brain and peripheral autonomic nervous system. They also are physiologic
      endothelial-derived relaxing factors for blood vessels. In the gastrointestinal
      pathway, NO and CO appear to function as coneurotransmitters, both stimulating
      soluble guanylyl cyclase to cause smooth muscle relaxation.

PMID- 11572960
TI  - Presynaptic kainate receptors at hippocampal mossy fiber synapses.
AB  - Hippocampal mossy fibers, which are the axons of dentate granule cells, form
      powerful excitatory synapses onto the proximal dendrites of CA3 pyramidal cells.
      It has long been known that high-affinity binding sites for kainate, a glutamate
      receptor agonist, are present on mossy fibers. Here we summarize recent
      experiments on the role of these presynaptic kainate receptors (KARs).
      Application of kainate has a direct effect on the amplitude of the
      extracellularly recorded fiber volley, with an enhancement by low concentrations
      and a depression by high concentrations. These effects are mediated by KARs,
      because they persist in the presence of the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor-selective antagonist GYKI 53655, but are blocked
      by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/KAR antagonist 6
      cyano-7-nitroquinoxaline-2,3-dione and the KAR antagonist SYM2081. The effects on
      the fiber volley are most likely caused by a depolarization of the fibers via the
      known ionotropic actions of KARs, because application of potassium mimics the
      effects. In addition to these effects on fiber excitability, low concentrations
      of kainate enhance transmitter release, whereas high concentrations depress
      transmitter release. Importantly, the synaptic release of glutamate from mossy
      fibers also activates these presynaptic KARs, causing an enhancement of the fiber
      volley and a facilitation of release that lasts for many seconds. This positive
      feedback contributes to the dramatic frequency facilitation that is
      characteristic of mossy fiber synapses. It will be interesting to determine how
      widespread facilitatory presynaptic KARs are at other synapses in the central
      nervous system.

PMID- 11572961
TI  - Retrograde signaling at central synapses.
AB  - Transcellular retrograde signaling from the postsynaptic target cell to the
      presynaptic neuron plays critical roles in the formation, maturation, and
      plasticity of synaptic connections. We here review recent progress in our
      understanding of the retrograde signaling at developing central synapses. Three
      forms of potential retrograde signals-membrane-permeant factors, membrane-bound
      factors, and secreted factors-have been implicated at both developing and mature
      synapses. Although many of these signals may be active constitutively, retrograde
      factors produced in association with activity-dependent synaptic plasticity,
      e.g., long-term potentiation and long-term depression, are of particular
      interest, because they may induce modification of neuronal excitability and
      synaptic transmission, functions directly related to the processing and storage
      of information in the nervous system.

PMID- 11572962
TI  - Controlling potassium channel activities: Interplay between the membrane and
      intracellular factors.
AB  - Neural signaling is based on the regulated timing and extent of channel opening;
      therefore, it is important to understand how ion channels open and close in
      response to neurotransmitters and intracellular messengers. Here, we examine this
      question for potassium channels, an extraordinarily diverse group of ion
      channels. Voltage-gated potassium (Kv) channels control action-potential
      waveforms and neuronal firing patterns by opening and closing in response to
      membrane-potential changes. These effects can be strongly modulated by
      cytoplasmic factors such as kinases, phosphatases, and small GTPases. A Kv alpha
      subunit contains six transmembrane segments, including an intrinsic voltage
      sensor. In contrast, inwardly rectifying potassium (Kir) channels have just two
      transmembrane segments in each of its four pore-lining alpha subunits. A variety
      of intracellular second messengers mediate transmitter and metabolic regulation
      of Kir channels. For example, Kir3 (GIRK) channels open on binding to the G
      protein betagamma subunits, thereby mediating slow inhibitory postsynaptic
      potentials in the brain. Our structure-based functional analysis on the
      cytoplasmic N-terminal tetramerization domain T1 of the voltage-gated channel,
      Kv1.2, uncovered a new function for this domain, modulation of voltage gating,
      and suggested a possible means of communication between second messenger pathways
      and Kv channels. A yeast screen for active Kir3.2 channels subjected to random
      mutagenesis has identified residues in the transmembrane segments that are
      crucial for controlling the opening of Kir3.2 channels. The identification of
      structural elements involved in potassium channel gating in these systems
      highlights principles that may be important in the regulation of other types of
      channels.

PMID- 11572963
TI  - Calcium regulation of neuronal gene expression.
AB  - Plasticity is a remarkable feature of the brain, allowing neuronal structure and
      function to accommodate to patterns of electrical activity. One component of
      these long-term changes is the activity-driven induction of new gene expression,
      which is required for both the long-lasting long-term potentiation of synaptic
      transmission associated with learning and memory, and the activity dependent
      survival events that help to shape and wire the brain during development. We have
      characterized molecular mechanisms by which neuronal membrane depolarization and
      subsequent calcium influx into the cytoplasm lead to the induction of new gene
      transcription. We have identified three points within this cascade of events
      where the specificity of genes induced by different types of stimuli can be
      regulated. By using the induction of the gene that encodes brain-derived
      neurotrophic factor (BDNF) as a model, we have found that the ability of a
      calcium influx to induce transcription of this gene is regulated by the route of
      calcium entry into the cell, by the pattern of phosphorylation induced on the
      transcription factor cAMP-response element (CRE) binding protein (CREB), and by
      the complement of active transcription factors recruited to the BDNF promoter.
      These results refine and expand the working model of activity-induced gene
      induction in the brain, and help to explain how different types of neuronal
      stimuli can activate distinct transcriptional responses.

PMID- 11572964
TI  - Sensory experience and sensory activity regulate chemosensory receptor gene
      expression in Caenorhabditis elegans.
AB  - Changes in the environment cause both short-term and long-term changes in an
      animal's behavior. Here we show that specific sensory experiences cause changes
      in chemosensory receptor gene expression that may alter sensory perception in the
      nematode Caenorhabditis elegans. Three predicted chemosensory receptor genes
      expressed in the ASI chemosensory neurons, srd-1, str-2, and str-3, are repressed
      by exposure to the dauer pheromone, a signal of crowding. Repression occurs at
      pheromone concentrations below those that induce formation of the alternative
      dauer larva stage, suggesting that exposure to pheromones can alter the
      chemosensory behaviors of non-dauer animals. In addition, ASI expression of srd
      1, but not str-2 and str-3, is induced by sensory activity of the ASI neurons.
      Expression of two receptor genes is regulated by developmental entry into the
      dauer larva stage. srd-1 expression in ASI neurons is repressed in dauer larvae.
      str-2 expression in dauer animals is induced in the ASI neurons, but repressed in
      the AWC neurons. The ASI and AWC neurons remodel in the dauer stage, and these
      results suggest that their sensory specificity changes as well. We suggest that
      experience-dependent changes in chemosensory receptor gene expression may modify
      olfactory behaviors.

PMID- 11572965
TI  - Presenilin, Notch, and the genesis and treatment of Alzheimer's disease.
AB  - Elucidation of the proteolytic processing of the amyloid beta-protein precursor
      (APP) has revealed that one of the two proteases (gamma-secretase) that cleave
      APP to release amyloid beta-protein (Abeta) is likely to be presenilin.
      Presenilin also mediates the gamma-secretase-like cleavage of Notch receptors to
      enable signaling by their cytoplasmic domains. Therefore, APP and Notch may be
      the first identified substrates of a unique intramembranous aspartyl protease
      that has presenilin as its active-site component. In view of the evidence for a
      central role of cerebral build-up of Abeta in the pathogenesis of Alzheimer's
      disease, this disorder appears to have arisen in the human population as a late
      life consequence of the conservation of a critical developmental pathway.

PMID- 11572966
TI  - DeltaFosB: a sustained molecular switch for addiction.
AB  - The longevity of some of the behavioral abnormalities that characterize drug
      addiction has suggested that regulation of neural gene expression may be involved
      in the process by which drugs of abuse cause a state of addiction. Increasing
      evidence suggests that the transcription factor DeltaFosB represents one
      mechanism by which drugs of abuse produce relatively stable changes in the brain
      that contribute to the addiction phenotype. DeltaFosB, a member of the Fos family
      of transcription factors, accumulates within a subset of neurons of the nucleus
      accumbens and dorsal striatum (brain regions important for addiction) after
      repeated administration of many kinds of drugs of abuse. Similar accumulation of
      DeltaFosB occurs after compulsive running, which suggests that DeltaFosB may
      accumulate in response to many types of compulsive behaviors. Importantly,
      DeltaFosB persists in neurons for relatively long periods of time because of its
      extraordinary stability. Therefore, DeltaFosB represents a molecular mechanism
      that could initiate and then sustain changes in gene expression that persist long
      after drug exposure ceases. Studies in inducible transgenic mice that overexpress
      either DeltaFosB or a dominant negative inhibitor of the protein provide direct
      evidence that DeltaFosB causes increased sensitivity to the behavioral effects of
      drugs of abuse and, possibly, increased drug seeking behavior. This work supports
      the view that DeltaFosB functions as a type of sustained "molecular switch" that
      gradually converts acute drug responses into relatively stable adaptations that
      contribute to the long-term neural and behavioral plasticity that underlies
      addiction.

PMID- 11572967
TI  - Glutamatergic modulation of hyperactivity in mice lacking the dopamine
      transporter.
AB  - In the brain, dopamine exerts an important modulatory influence over behaviors
      such as emotion, cognition, and affect as well as mechanisms of reward and the
      control of locomotion. The dopamine transporter (DAT), which reuptakes the
      released neurotransmitter into presynaptic terminals, is a major determinant of
      the intensity and duration of the dopaminergic signal. Knockout mice lacking the
      dopamine transporter (DAT-KO mice) display marked changes in dopamine homeostasis
      that result in elevated dopaminergic tone and pronounced locomotor hyperactivity.
      A feature of DAT-KO mice is that their hyperactivity can be inhibited by
      psychostimulants and serotonergic drugs. The pharmacological effect of these
      drugs occurs without any observable changes in dopaminergic parameters,
      suggesting that other neurotransmitter systems in addition to dopamine might
      contribute to the control of locomotion in these mice. We report here that the
      hyperactivity of DAT-KO mice can be markedly further enhanced when N-methyl-d
      aspartate receptor-mediated glutamatergic transmission is blocked. Conversely,
      drugs that enhance glutamatergic transmission, such as positive modulators of l
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate glutamate receptors,
      suppress the hyperactivity of DAT-KO mice. Interestingly, blockade of N- methyl-d
      aspartate receptors prevented the inhibitory effects of both psychostimulant and
      serotonergic drugs on hyperactivity. These findings support the concept of a
      reciprocal functional interaction between dopamine and glutamate in the basal
      ganglia and suggest that agents modulating glutamatergic transmission may
      represent an approach to manage conditions associated with dopaminergic
      dysfunction.

PMID- 11572968
TI  - Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity
      and excitotoxicity.
AB  - Zinc is coreleased with glutamate from excitatory nerve terminals throughout the
      central nervous system and acutely inhibits N-methyl-d-aspartate (NMDA) receptor
      activation. Here we report that cultured murine cortical neurons briefly exposed
      to sublethal concentrations of zinc developed increased intracellular free Na(+),
      phosphorylation of Src kinase at tyrosine 220, and tyrosine phosphorylation of
      NMDA receptor 2A/2B subunits, in a fashion sensitive to the Src family kinase
      inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, PP2.
      Functionally, this zinc exposure produced a delayed increase in NMDA receptor
      current in perforated patch but not conventional whole-cell recordings, as well
      as an increase in NMDA receptor-mediated cell death. These observations suggest
      that the effect of synaptically released zinc on neuronal NMDA receptors may be
      biphasic: acute block, followed by Src family kinase-mediated up-regulation of
      NMDA receptor activity and cytotoxicity.

PMID- 11572970
TI  - Ordered upwind methods for static Hamilton-Jacobi equations.
AB  - We introduce a family of fast ordered upwind methods for approximating solutions
      to a wide class of static Hamilton-Jacobi equations with Dirichlet boundary
      conditions. Standard techniques often rely on iteration to converge to the
      solution of a discretized version of the partial differential equation. Our fast
      methods avoid iteration through a careful use of information about the
      characteristic directions of the underlying partial differential equation. These
      techniques are of complexity O(M log M), where M is the total number of points in
      the domain. We consider anisotropic test problems in optimal control, seismology,
      and paths on surfaces.

PMID- 11572969
TI  - Regulation of cyclin-dependent kinase 5 and casein kinase 1 by metabotropic
      glutamate receptors.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a multifunctional neuronal protein kinase
      that is required for neurite outgrowth and cortical lamination and that plays an
      important role in dopaminergic signaling in the neostriatum through
      phosphorylation of Thr-75 of DARPP-32 (dopamine and cAMP-regulated
      phosphoprotein, molecular mass 32 kDa). Casein kinase 1 (CK1) has been implicated
      in a variety of cellular functions such as DNA repair, circadian rhythm, and
      intracellular trafficking. In the neostriatum, CK1 has been found to
      phosphorylate Ser-137 of DARPP-32. However, first messengers for the regulation
      of Cdk5 or CK1 have remained unknown. Here we report that both Cdk5 and CK1 are
      regulated by metabotropic glutamate receptors (mGluRs) in neostriatal neurons.
      (S)-3,5-dihydroxyphenylglycine (DHPG), an agonist for group I mGluRs, increased
      Cdk5 and CK1 activities in neostriatal slices, leading to the enhanced
      phosphorylation of Thr-75 and Ser-137 of DARPP-32, respectively. The effect of
      DHPG on Thr-75, but not on Ser-137, was blocked by a Cdk5-specific inhibitor,
      butyrolactone. In contrast, the effects of DHPG on both Thr-75 and Ser-137 were
      blocked by CK1-7 and IC261, specific inhibitors of CK1, suggesting that
      activation of Cdk5 by mGluRs requires CK1 activity. In support of this
      possibility, the DHPG-induced increase in Cdk5 activity, measured in extracts of
      neostriatal slices, was abolished by CK1-7 and IC261. Treatment of acutely
      dissociated neurons with DHPG enhanced voltage-dependent Ca(2+) currents. This
      enhancement was eliminated by either butyrolactone or CK1-7 and was absent in
      DARPP-32 knockout mice. Together these results indicate that a CK1-Cdk5-DARPP-32
      cascade may be involved in the regulation by mGluR agonists of Ca(2+) channels.

PMID- 11572971
TI  - A single amino acid serves as an affinity switch between the receptor and the
      binding protein of corticotropin-releasing factor: implications for the design of
      agonists and antagonists.
AB  - In view of the observation that corticotropin-releasing factor (CRF) affects
      several brain functions through at least two subtypes of G protein-dependent
      receptors and a binding protein (CRFBP), we have developed synthetic strategies
      to provide enhanced binding specificity. Human/rat CRF (h/rCRF) and the CRF-like
      peptide sauvagine (Svg), differing in their affinities to CRFBP by two orders of
      magnitude, were used to identify the residues determining binding to CRFBP. By
      amino acid exchanges, it was found that Ala(22) of h/rCRF was responsible for
      this peptide's high affinity to CRFBP, whereas Glu(21) located in the equivalent
      position of Svg prevented high affinity binding to CRFBP. Accordingly,
      [Glu(22)]h/rCRF was not bound with high affinity to CRFBP in contrast to
      [Ala(21)]Svg, which exhibited such high affinity. Furthermore, the affinity of
      both peptides to either CRF receptor (CRFR) subtype was not reduced by these
      replacements, and their subtype preference was not changed. Thus, exchange of Ala
      and Glu and vice versa in positions 22 and 21 of h/rCRF and Svg, respectively,
      serves as a switch discriminating between CRFBP and CRFR. On the basis of this
      switch function, development of new specific CRF agonists and antagonists is
      expected to be facilitated. One application was the modification of the CRF
      antagonist astressin (Ast), whose employment in animal experiments is limited by
      its low solubility in cerebrospinal fluid. Introduction of Glu residues into Ast
      generated with [Glu(11,16)]Ast an acidic astressin, which efficiently antagonized
      in vivo the CRFR1-dependent reduction of locomotion induced by ovine CRF without
      detectable binding to CRFBP.

PMID- 11572972
TI  - Can coelenterates make coelenterazine? Dietary requirement for luciferin in
      cnidarian bioluminescence.
AB  - In the calcium-activated photoprotein aequorin, light is produced by the
      oxidation of coelenterazine, the luciferin used by at least seven marine phyla.
      However, despite extensive research on photoproteins, there has been no evidence
      to indicate the origin of coelenterazine within the phylum Cnidaria. Here we
      report that the hydromedusa Aequorea victoria is unable to produce its own
      coelenterazine and is dependent on a dietary supply of this luciferin for
      bioluminescence. Although they contain functional apophotoproteins, medusae
      reared on a luciferin-free diet are unable to produce light unless provided with
      coelenterazine from an external source. This evidence regarding the origins of
      luciferin in Cnidaria has implications for the evolution of bioluminescence and
      for the extensive use of coelenterazine among marine organisms.

PMID- 11572973
TI  - Definition of EGF-like, closely interacting modules that bear activation epitopes
      in integrin beta subunits.
AB  - Integrin beta subunits contain four cysteine-rich repeats in a long extracellular
      stalk that connects the headpiece to the membrane. Most mAbs to integrin
      activation epitopes map to these repeats, and they are important in propagating
      conformational signals from the membrane/cytosol to the ligand-binding headpiece.
      Sequence analysis of a protein containing only 10 integrin-like, cysteine-rich
      repeats suggests that these repeats start one cysteine earlier than previously
      reported. By using the new repeat boundaries, statistically significant sequence
      homology to epidermal growth factor-like domains is found, and a disulfide bond
      connectivity of the eight cysteines is predicted that differs in three of four
      disulfides from a previous prediction of epidermal growth factor-like modules
      [Berg, R. W., Leung, E., Gough, S., Morris, C., Yao, W.-P., Wang, S.-x., Ni, J. &
      Krissansen, G. W. (1999) Genomics 56, 169-178]. N-terminally truncated beta2
      integrin stalk fragments were well expressed and secreted from 293 T cells when
      they began at repeat boundaries but not when they began one cysteine earlier or
      later. Furthermore, peptides that correspond to module 3 or modules 2 + 3 were
      expressed in bacteria and refolded. The module 2 + 3 fragment was as reactive
      with three mAbs to activation epitopes as a beta2 fragment expressed in
      eukaryotic cells, indicating a native fold. Only one residue intervenes between
      the last cysteine of one module and the first cysteine of the next. This
      arrangement is consistent with a tight intermodule connection, a prerequisite for
      signal propagation from the membrane to the ligand binding headpiece.

PMID- 11572974
TI  - Design of potent inhibitors of HIV-1 entry from the gp41 N-peptide region.
AB  - The HIV-1 gp41 envelope glycoprotein promotes fusion of the virus and cell
      membranes through the formation of a trimer-of-hairpins structure, in which the
      amino- and carboxyl-terminal regions of the gp41 ectodomain are brought together.
      Synthetic peptides derived from these two regions (called N and C peptides,
      respectively) inhibit HIV-1 entry. In contrast to C peptides, which inhibit in
      the nanomolar range, N peptides are weak inhibitors with IC(50) values in the
      micromolar range. To test the hypothesis that the weak inhibition of N peptides
      results from their tendency to aggregate, we have constructed chimeric variants
      of the N-peptide region of gp41 in which soluble trimeric coiled coils are fused
      to portions of the gp41 N peptide. These molecules, which present the N peptide
      in a trimeric coiled-coil conformation, are remarkably more potent inhibitors
      than the N peptides themselves and likely target the carboxyl-terminal region of
      the gp41 ectodomain. The best inhibitors described here inhibit HIV-1 entry at
      nanomolar concentrations.

PMID- 11572975
TI  - A computational analysis of sequence features involved in recognition of short
      introns.
AB  - Splicing of short introns by the nuclear pre-mRNA splicing machinery is thought
      to proceed via an "intron definition" mechanism, in which the 5' and 3' splice
      sites (5'ss, 3'ss, respectively) are initially recognized and paired across the
      intron. Here, we describe a computational analysis of sequence features involved
      in recognition of short introns by using available transcript data from five
      eukaryotes with complete or nearly complete genomic sequences. The information
      content of five different transcript features was measured by using methods from
      information theory, and Monte Carlo simulations were used to determine the amount
      of information required for accurate recognition of short introns in each
      organism. We conclude: (i) that short introns in Drosophila melanogaster and
      Caenorhabditis elegans contain essentially all of the information for their
      recognition by the splicing machinery, and computer programs that simulate
      splicing specificity can predict the exact boundaries of approximately 95% of
      short introns in both organisms; (ii) that in yeast, the 5'ss, branch signal, and
      3'ss can accurately identify intron locations but do not precisely determine the
      location of 3' cleavage in every intron; and (iii) that the 5'ss, branch signal,
      and 3'ss are not sufficient to accurately identify short introns in plant and
      human transcripts, but that specific subsets of candidate intronic enhancer
      motifs can be identified in both human and Arabidopsis that contribute
      dramatically to the accuracy of splicing simulators.

PMID- 11572976
TI  - Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome
      replication cycle.
AB  - Cdc6p and the origin recognition complex (ORC) are essential for assembly of a
      pre-replicative complex (preRC) at origins of replication, before the initiation
      of DNA synthesis. In the absence of Cdc6p, cells fail to initiate DNA replication
      and undergo a "reductional" mitosis, in which the unreplicated chromosomes are
      randomly segregated to the spindle poles. We show here that the cells harboring a
      mutation in the essential Cdc6p Walker A-box arrest in late mitosis, probably at
      anaphase. This cell cycle block requires either the three Cdc28p phosphorylation
      sites within the N terminus of Cdc6p or a short region (aa 8-17) that contains a
      Cy (Cyclin) interaction sequence. These same two Cdc6p mutants that allow a
      reductional mitosis are defective in binding Cdc28p kinase. In addition to Cdc6p,
      ORC also binds to cyclin-dependent kinases (CDKs). Interestingly, Sic1p, a CDK
      inhibitor protein, blocked the S phase-specific Cdc28p-Clb5p kinase from
      interacting with ORC, but did not prevent the G(1)-specific Cdc28p-Cln2p kinase
      ORC interaction. We suggest that ORC, Cdc6p, and Sic1p bind to different CDKs in
      a cell cycle-dependent manner to temporally regulate events that (i) allow preRC
      formation after mitosis, (ii) prevent mitosis before DNA replication can occur,
      and (iii) promote initiation of DNA replication.

PMID- 11572977
TI  - Purification and characterization of human DNA damage checkpoint Rad complexes.
AB  - Checkpoint Rad proteins function early in the DNA damage checkpoint signaling
      cascade to arrest cell cycle progression in response to DNA damage. This
      checkpoint ensures the transmission of an intact genetic complement to daughter
      cells. To learn about the damage sensor function of the human checkpoint Rad
      proteins, we purified a heteropentameric complex composed of hRad17-RFCp36-RFCp37
      RFCp38-RFCp40 (hRad17-RFC) and a heterotrimeric complex composed of hRad9-hHus1
      hRad1 (checkpoint 9-1-1 complex). hRad17-RFC binds to DNA, with a preference for
      primed DNA and possesses weak ATPase activity that is stimulated by primed DNA
      and single-stranded DNA. hRad17-RFC forms a complex with the 9-1-1 heterotrimer
      reminiscent of the replication factor C/proliferating cell nuclear antigen clamp
      loader/sliding clamp complex of the replication machinery. These findings
      constitute biochemical support for models regarding the roles of checkpoint Rads
      as damage sensors in the DNA damage checkpoint response of human cells.

PMID- 11572978
TI  - On the nature of a glassy state of matter in a hydrated protein: Relation to
      protein function.
AB  - Diverse biochemical and biophysical experiments indicate that all proteins,
      regardless of size or origin, undergo a dynamic transition near 200 K. The cause
      of this shift in dynamic behavior, termed a "glass transition," and its relation
      to protein function are important open questions. One explanation postulated for
      the transition is solidification of correlated motions in proteins below the
      transition. We verified this conjecture by showing that crambin's radius of
      gyration (Rg) remains constant below approximately 180 K. We show that both atom
      position and dynamics of protein and solvent are physically coupled, leading to a
      novel cooperative state. This glassy state is identified by negative slopes of
      the Debye-Waller (B) factor vs. temperature. It is composed of multisubstate side
      chains and solvent. Based on generalization of Adam-Gibbs' notion of a
      cooperatively rearranging region and decrease of the total entropy with
      temperature, we calculate the slope of the Debye-Waller factor. The results are
      in accord with experiment.

PMID- 11572979
TI  - Disordered to ordered folding in the regulation of diphtheria toxin repressor
      activity.
AB  - Understanding how metal binding regulates the activity of the diphtheria toxin
      repressor protein (DtxR) requires information about the structure in solution. We
      have prepared a DtxR mutant construct with three additional N-terminal residues,
      Gly-Ser-His-DtxR(Cys-102 --> Asp), that retains metal-binding capabilities, but
      remains monomeric in solution and does not bind DNA under conditions that effect
      dimerization and DNA binding in the functional DtxR(Cys-102 --> Asp) construct.
      Although the interaction properties of this inactive mutant in solution are very
      different from that of active repressors, crystallization imposes the same
      dimeric structure as observed in all crystal forms of the active repressor with
      and without bound metal. Our solution NMR analyses of active and inactive metal
      free diphtheria toxin repressors demonstrate that whereas the C-terminal one
      third of the protein is well ordered, the N-terminal two-thirds exhibits
      conformational flexibility and exists as an ensemble of structural substates with
      undefined tertiary structure. Fluorescence binding assays with 1-anilino
      naphthalene-8-sulfonic acid (ANS) confirm that the highly alpha-helical N
      terminal two-thirds of the apoprotein is molten globule-like in solution. Binding
      of divalent metal cations induces a substantial conformational reorganization to
      a more ordered state, as evidenced by changes in the NMR spectra and ANS binding.
      The evident disorder to order transition upon binding of metal in solution is in
      contrast to the minor conformational changes seen comparing apo- and holo-DtxR
      crystal structures. Disordered to ordered folding appears to be a general
      mechanism for regulating specific recognition in protein action and this
      mechanism provides a plausible explanation for how metal binding controls the
      DtxR repressor activity.

PMID- 11572980
TI  - Spatially localized generation of nucleotide sequence-specific DNA damage.
AB  - Psoralens linked to triplex-forming oligonucleotides (psoTFOs) have been used in
      conjunction with laser-induced two-photon excitation (TPE) to damage a specific
      DNA target sequence. To demonstrate that TPE can initiate photochemistry
      resulting in psoralen-DNA photoadducts, target DNA sequences were incubated with
      psoTFOs to form triple-helical complexes and then irradiated in liquid solution
      with pulsed 765-nm laser light, which is half the quantum energy required for
      conventional one-photon excitation, as used in psoralen + UV A radiation (320-400
      nm) therapy. Target DNA acquired strand-specific psoralen monoadducts in a light
      dose-dependent fashion. To localize DNA damage in a model tissue-like medium, a
      DNA-psoTFO mixture was prepared in a polyacrylamide gel and then irradiated with
      a converging laser beam targeting the rear of the gel. The highest number of
      photoadducts formed at the rear while relatively sparing DNA at the front of the
      gel, demonstrating spatial localization of sequence-specific DNA damage by TPE.
      To assess whether TPE treatment could be extended to cells without significant
      toxicity, cultured monolayers of normal human dermal fibroblasts were incubated
      with tritium-labeled psoralen without TFO to maximize detectable damage and
      irradiated by TPE. DNA from irradiated cells treated with psoralen exhibited a 4-
      to 7-fold increase in tritium activity relative to untreated controls. Functional
      survival assays indicated that the psoralen-TPE treatment was not toxic to cells.
      These results demonstrate that DNA damage can be simultaneously manipulated at
      the nucleotide level and in three dimensions. This approach for targeting
      photochemical DNA damage may have photochemotherapeutic applications in skin and
      other optically accessible tissues.

PMID- 11572981
TI  - Focal adhesion kinase is involved in mechanosensing during fibroblast migration.
AB  - Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase localized
      at focal adhesions and is believed to mediate adhesion-stimulated effects.
      Although ablation of FAK impairs cell movement, it is not clear whether FAK might
      be involved in the guidance of cell migration, a role consistent with its
      putative regulatory function. We have transfected FAK-null fibroblasts with FAK
      gene under the control of the tetracycline repression system. Cells were cultured
      on flexible polyacrylamide substrates for the detection of traction forces and
      the application of mechanical stimulation. Compared with control cells expressing
      wild-type FAK, FAK-null cells showed a decrease in migration speed and
      directional persistence. In addition, whereas FAK-expressing cells responded to
      exerted forces by reorienting their movements and forming prominent focal
      adhesions, FAK-null cells failed to show such responses. Furthermore, FAK-null
      cells showed impaired responses to decreases in substrate flexibility, which
      causes control cells to generate weaker traction forces and migrate away from
      soft substrates. Cells expressing Y397F FAK, which cannot be phosphorylated at a
      key tyrosine site, showed similar defects in migration pattern and force-induced
      reorientation as did FAK-null cells. However, other aspects of F397-FAK cells,
      including the responses to substrate flexibility and the amplification of focal
      adhesions upon mechanical stimulation, were similar to that of control cells. Our
      results suggest that FAK plays an important role in the response of migrating
      cells to mechanical input. In addition, phosphorylation at Tyr-397 is required
      for some, but not all, of the functions of FAK in cell migration.

PMID- 11572982
TI  - Digital in-line holography for biological applications.
AB  - Digital in-line holography with numerical reconstruction has been developed into
      a new tool, specifically for biological applications, that routinely achieves
      both lateral and depth resolution, at least at the micron level, in three
      dimensional imaging. The experimental and numerical procedures have been
      incorporated into a program package with a very fast reconstruction algorithm
      that is now capable of real-time reconstruction. This capability is demonstrated
      for diverse objects, such as suspension of microspheres and biological samples
      (diatom, the head of Drosophila melanogaster), and the advantages are discussed
      by comparing holographic reconstructions with images taken by using conventional
      compound light microscopy.

PMID- 11572983
TI  - Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell
      death and survival signals.
AB  - BH3-only proteins function at a proximal point in a conserved cell death pathway
      by binding, through their BH3 domains, to other Bcl-2 family members and
      triggering mitochondrial events associated with apoptosis. Here, we describe a
      strongly pro-apoptotic BH3-only protein, designated Bbc3, whose expression
      increases in response to diverse apoptotic stimuli. bbc3 mRNA levels were induced
      by exposure to DNA-damaging agents and by wild-type p53, which mediates DNA
      damage-induced apoptosis. p53 transactivated bbc3 through consensus p53 binding
      sites within the bbc3 promoter region, indicating that bbc3 is a direct target of
      p53. Additionally, bbc3 mRNA was induced by p53-independent apoptotic stimuli,
      including dexamethasone treatment of thymocytes, and serum deprivation of tumor
      cells. Insulin-like growth factor-1 and epidermal growth factor, growth factors
      with broad anti-apoptotic activity, were each sufficient to suppress Bbc3
      expression in serum-starved tumor cells. These results suggest that the
      transcriptional regulation of bbc3 contributes to the transduction of diverse
      cell death and survival signals.

PMID- 11572984
TI  - Self-organization of a propulsive actin network as an evolutionary process.
AB  - The leading edge of motile cells is propelled by polymerization of actin
      filaments according to a dendritic nucleation/array treadmilling mechanism.
      However, little attention has been given to the origin and maintenance of the
      dendritic array. Here we develop and test a population-kinetics model that
      explains the organization of actin filaments in terms of the reproduction of
      dendritic units. The life cycle of an actin filament consists of dendritic
      nucleation on another filament (birth), elongation by addition of actin subunits
      and, finally, termination of filament growth by capping protein (death). The
      regularity of branch angle between daughter and mother filaments endows filaments
      with heredity of their orientation. Fluctuations of branch angle that become
      fixed in the actin network create errors of orientation (mutations) that may be
      inherited. In our model, birth and death rates depend on filament orientation,
      which then becomes a selectable trait. Differential reproduction and elimination
      of filaments, or natural selection, leads to the evolution of a filament pattern
      with a characteristic distribution of filament orientations. We develop a
      procedure based on the Radon transform for quantitatively analyzing actin
      networks in situ and show that the experimental results are in agreement with the
      distribution of filament orientations predicted by our model. We conclude that
      the propulsive actin network can be understood as a self-organizing
      supramolecular ensemble shaped by the evolution of dendritic lineages through
      natural selection of their orientation.

PMID- 11572985
TI  - Germ cell selection in genetic mosaics in Drosophila melanogaster.
AB  - Heritable mutations in the germ line lead to genetically heterogeneous, or
      mosaic, gonads. Many of the genes used in germ-line development also play roles
      in somatic development [Saffman, E. E. & Lasko, P. (1999) Cell. Mol. Life Sci.
      55, 1141-1163]. Mutations in these genes may have cellular phenotypes throughout
      germ-line development leading to their differential elimination or survival, as
      has been observed in somatic cells [Morata, G. & Ripoll, P. (1975) Dev. Biol. 42,
      211-221]. We investigate whether mutations in heterozygosis are subject to
      pregametic selection in the germ line. We initiated clones of wild-type
      homozygous cells at different stages of development in gonads heterozygous for
      eight different recessive chromosome deficiencies. Here we show that cell
      selection takes place in mosaic germ-line populations. This phenomenon represents
      a level of selection that precedes and conditions subsequent zygotic selection by
      affecting the genes available in the gametic population.

PMID- 11572986
TI  - Evidence that the WNT-inducible growth arrest-specific gene 1 encodes an
      antagonist of sonic hedgehog signaling in the somite.
AB  - The dorsal-ventral polarity of the somite is controlled by antagonistic signals
      from the dorsal neural tube/surface ectoderm, mediated by WNTs, and from the
      ventral notochord, mediated by sonic hedgehog (SHH). Each factor can act over a
      distance greater than a somite diameter in vitro, suggesting they must limit each
      other's actions within their own patterning domains in vivo. We show here that
      the growth-arrest specific gene 1 (Gas1), which is expressed in the dorsal
      somite, is induced by WNTs and encodes a protein that can bind to SHH.
      Furthermore, ectopic expression of Gas1 in presomitic cells attenuates the
      response of these cells to SHH in vitro. Taken together, these data suggest that
      GAS1 functions to reduce the availability of active SHH within the dorsal somite.

PMID- 11572987
TI  - Contribution of individual random mutations to genotype-by-environment
      interactions in Escherichia coli.
AB  - Numerous studies have shown genotype-by-environment (GxE) interactions for traits
      related to organismal fitness. However, the genetic architecture of the
      interaction is usually unknown because these studies used genotypes that differ
      from one another by many unknown mutations. These mutations were also present as
      standing variation in populations and hence had been subject to prior selection.
      Based on such studies, it is therefore impossible to say what fraction of new,
      random mutations contributes to GxE interactions. In this study, we measured the
      fitness in four environments of 26 genotypes of Escherichia coli, each containing
      a single random insertion mutation. Fitness was measured relative to their common
      progenitor, which had evolved on glucose at 37 degrees C for the preceding 10,000
      generations. The four assay environments differed in limiting resource and
      temperature (glucose, 28 degrees C; maltose, 28 degrees C; glucose, 37 degrees C;
      and maltose, 37 degrees C). A highly significant interaction between mutation and
      resource was found. In contrast, there was no interaction involving temperature.
      The resource interaction reflected much higher among mutation variation for
      fitness in maltose than in glucose. At least 11 mutations (42%) contributed to
      this GxE interaction through their differential fitness effects across resources.
      Beneficial mutations are generally thought to be rare but, surprisingly, at least
      three mutations (12%) significantly improved fitness in maltose, a resource novel
      to the progenitor. More generally, our findings demonstrate that GxE interactions
      can be quite common, even for genotypes that differ by only one mutation and in
      environments differing by only a single factor.

PMID- 11572988
TI  - A growth cost of begging in captive canary chicks.
AB  - Nestling birds solicit food from adults by using begging displays that appear
      paradoxically costly and wasteful. Theoretical work suggests that the evolution
      of such exuberant offspring behavior reflects parent-offspring conflict over the
      supply of parental investment. Originally, extravagant begging was seen as a
      means of psychological trickery by which offspring could wheedle additional
      resources from resistant parents. Subsequently, costly begging came to be viewed
      as the hallmark of resolved parent-offspring conflict, serving either to prevent
      escalated scramble competition or to enforce honest signaling. However, the
      theoretical assumption of costly solicitation has been called into question by
      the low level of energy expenditure measured empirically during begging. This
      finding has prompted new theoretical work that shows that begging can be cost
      free and yet still resolve parent-offspring conflict. Here, I report that begging
      is more costly than recent work suggests. My experimental evidence from captive
      canaries demonstrates a marginal cost of begging through impaired growth.
      Furthermore, I argue that previous studies of energy expenditure during
      solicitation do not measure the cost of begging, as defined theoretically. More
      generally, my results may account for the evolution of nestling growth rates, as
      well as the observation that begging is typically most flamboyant in older
      offspring.

PMID- 11572989
TI  - WWOX: a candidate tumor suppressor gene involved in multiple tumor types.
AB  - We previously reported the construction of a P1-derived artificial chromosome
      (PAC) contig encompassing a set of homozygous deletions of chromosome 16q23-24.1
      found in primary ovarian tumor material and several tumor cell lines. Using these
      PAC clones in a cDNA selection experiment, we have isolated a Sau3A fragment
      homologous to the WWOX transcript (GenBank accession no. ) from normal human
      ovarian surface epithelial (HOSE) cells. We demonstrate the homozygous deletion
      of WWOX exons from ovarian cancer cells and three different tumor cell lines. We
      also identify an internally deleted WWOX transcript from a further primary
      ovarian tumor. In three of these samples the deletions result in frameshifts, and
      in each case the resulting WWOX transcripts lack part, or all, of the short chain
      dehydrogenase domain and the putative mitochondrial localization signal.
      Sequencing revealed several missense polymorphisms in tumor cell lines and
      identified a high level of single nucleotide polymorphism (SNP) within the WWOX
      gene. This evidence strengthens the case for WWOX as a tumor suppressor gene in
      ovarian cancer and other tumor types.

PMID- 11572990
TI  - Expression of the REB transcriptional activator in rice grains improves the yield
      of recombinant proteins whose genes are controlled by a Reb-responsive promoter.
AB  - The gene encoding the rice transcription factor, REB (rice endosperm bZIP) was
      cloned from a bacterial artificial chromosome library of rice. The cloned 6,227
      bp-long Reb gene is composed of six exons and five introns and is flanked by a
      1.2-kb 5' promoter and a 1.2-kb 3' terminator region. The function of the Reb
      gene was explored by a transient assay by using a rice immature endosperm system.
      The effector constructs containing the native gene or fusion genes linking Reb to
      the rice actin (Act) or globulin (Glb) gene promoters and the reporter gene
      construct Glb-beta-glucuronidase (GUS) were used in this study. When these
      effector constructs were cotransferred with the reporter uidA gene encoding GUS
      under the control of the Glb promoter into immature rice endosperm cells, the Glb
      promoter was activated. The transient GUS expression was 2.0 to 2.5-fold higher
      with the effector construct than without. When the upstream activation sequence
      containing the GCCACGT(A/C)AG motifs of the Glb promoter was deleted, the
      activation by REB was abolished. On the other hand, a gain-of-function experiment
      showed that inserting the upstream activation sequence into the glutelin-1 (Gt1)
      promoter made it responsive to activation by REB. When cotransformed with Reb
      gene, mature transgenic rice grains containing the human lysozyme gene driven by
      the Glb promoter produced 3.7-fold more lysozyme. Accumulation of recombinant
      lysozyme in mature seed ranged from 30.57 to 279.61 microg.mg(-1) total soluble
      protein in individual transformants from 30 independent transformation events.
      Thus, our results show that REB is not only a transcriptional activator, it can
      also be used to increase the expression of recombinant protein in transgenic rice
      grains.

PMID- 11572991
TI  - Drought- and salt-tolerant plants result from overexpression of the AVP1 H+-pump.
AB  - Transgenic plants overexpressing the vacuolar H(+)-pyrophosphatase are much more
      resistant to high concentrations of NaCl and to water deprivation than the
      isogenic wild-type strains. These transgenic plants accumulate more Na(+) and
      K(+) in their leaf tissue than the wild type. Moreover, direct measurements on
      isolated vacuolar membrane vesicles derived from the AVP1 transgenic plants and
      from wild type demonstrate that the vesicles from the transgenic plants have
      enhanced cation uptake. The phenotypes of the AVP1 transgenic plants suggest that
      increasing the vacuolar proton gradient results in increased solute accumulation
      and water retention. Presumably, sequestration of cations in the vacuole reduces
      their toxic effects. Genetically engineered drought- and salt-tolerant plants
      could provide an avenue to the reclamation of farmlands lost to agriculture
      because of salinity and a lack of rainfall.

PMID- 11572992
TI  - Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo
      dGTPase.
AB  - Oxygen radicals, which can be produced through normal cellular metabolism, are
      thought to play an important role in mutagenesis and tumorigenesis. Among various
      classes of oxidative DNA damage, 8-oxo-7,8-dihydroguanine (8-oxoG) is most
      important because of its abundance and mutagenicity. The MTH1 gene encodes an
      enzyme that hydrolyzes 8-oxo-dGTP to monophosphate in the nucleotide pool,
      thereby preventing occurrence of transversion mutations. By means of gene
      targeting, we have established MTH1 gene-knockout cell lines and mice. When
      examined 18 months after birth, a greater number of tumors were formed in the
      lungs, livers, and stomachs of MTH1-deficient mice, as compared with wild-type
      mice. The MTH1-deficient mouse will provide a useful model for investigating the
      role of the MTH1 protein in normal conditions and under oxidative stress.

PMID- 11572993
TI  - Increased levels of forkhead box M1B transcription factor in transgenic mouse
      hepatocytes prevent age-related proliferation defects in regenerating liver.
AB  - The forkhead box (Fox) family of transcription factors share homology in the
      winged helix/forkhead DNA-binding domain and play important roles in regulating
      cellular proliferation, differentiation, longevity, and cellular transformation.
      Forkhead box M1B (FoxM1B) is a ubiquitously expressed member of the Fox
      transcription factor family whose expression is restricted to proliferating cells
      and that mediates hepatocyte entry into DNA synthesis and mitosis during liver
      regeneration. Recent cDNA microarray studies indicated that age-related defects
      in cellular proliferation are associated with diminished expression of the FoxM1B
      transcription factor. Here, we show that increased levels of FoxM1B in
      regenerating liver of old transgenic mice restore the sharp peaks in hepatocyte
      DNA replication and mitosis that are the hallmarks of young regenerating mouse
      liver. Restoration of the young regenerating liver phenotype is associated with
      increased expression of numerous cell cycle regulatory genes that include cyclin
      D1, cyclin A2, cyclin F, cyclin B1, cyclin B2, Cdc25B, and p55cdc. Cotransfection
      assays in the human hepatoma HepG2 cell line demonstrated that FoxM1B protein
      stimulated expression of both the cyclin B1 and cyclin D1 promoters, suggesting
      that these cyclin genes are a direct FoxM1B transcriptional target. These results
      suggest that FoxM1B controls the transcriptional network of genes that are
      essential for cell division and exit from mitosis. Our results indicate that
      reduced expression of the FoxM1B transcription factor contributes to the decline
      in cellular proliferation observed in the aging process.

PMID- 11572995
TI  - Ultrasensitive detection and identification of fluorescent molecules by FCS:
      impact for immunobiology.
AB  - An experimental application of fluorescence correlation spectroscopy is presented
      for the detection and identification of fluorophores and auto-Abs in solution.
      The recording time is between 2 and 60 sec. Because the actual number of
      molecules in the unit volume (confocal detection volume of about 1 fl) is integer
      or zero, the fluorescence generated by the molecules is discontinuous when single
      molecule sensitivity is achieved. We first show that the observable probability,
      N, to find a single fluorescent molecule in the very tiny space element of the
      unit volume is Poisson-distributed below a critical bulk concentration c*. The
      measured probability means we have traced, for example, 5 x 10(10) fluorophore
      molecules per ml of bulk solution. The probability is related to the average
      frequency, C, that the volume of detection contains a single fluorescent molecule
      and to the concentration, c, of the bulk solution. The analytical sensitivity of
      an assay is calculated from the average frequency C. In the Goodpasture
      experiment, we determined as analytical sensitivity a probability of 99.1% of
      identifying one single immune complex. Under these conditions, a single molecule
      event is proven. There exist no instrumental assumptions of our approach on which
      the experiment itself, the theoretical background, or the conclusion are based.
      Our results open up a broad field for analytics and diagnostics in solution,
      especially in immunology.

PMID- 11572994
TI  - Fine-scale mapping of a locus for severe bipolar mood disorder on chromosome
      18p11.3 in the Costa Rican population.
AB  - We have searched for genes predisposing to bipolar disorder (BP) by studying
      individuals with the most extreme form of the affected phenotype, BP-I,
      ascertained from the genetically isolated population of the Central Valley of
      Costa Rica (CVCR). The results of a previous linkage analysis on two extended
      CVCR BP-I pedigrees, CR001 and CR004, and of linkage disequilibrium (LD) analyses
      of a CVCR population sample of BP-I patients implicated a candidate region on
      18p11.3. We further investigated this region by creating a physical map and
      developing 4 new microsatellite and 26 single-nucleotide polymorphism markers for
      typing in the pedigree and population samples. We report the results of fine
      scale association analyses in the population sample, as well as evaluation of
      haplotypes in pedigree CR001. Our results suggest a candidate region containing
      six genes but also highlight the complexities of LD mapping of common disorders.

PMID- 11572996
TI  - Transgenic rescue implicates beta2-microglobulin as a diabetes susceptibility
      gene in nonobese diabetic (NOD) mice.
AB  - Type 1 diabetes in both humans and nonobese diabetic (NOD) mice results from T
      cell-mediated autoimmune destruction of insulin-producing pancreatic beta cells.
      Linkage studies have shown that type 1 diabetes in NOD mice is a polygenic
      disease involving more than 15 chromosomal susceptibility regions. Despite
      extensive investigation, the identification of individual susceptibility genes
      either within or outside the major histocompatibility complex region has proven
      problematic because of the limitations of linkage analysis. In this paper, we
      provide evidence implicating a single diabetes susceptibility gene, which lies
      outside the major histocompatibility complex region. Using allelic reconstitution
      by transgenic rescue, we show that NOD mice expressing the beta(2) microglobulin
      (beta(2)M)(a) allele develop diabetes, whereas NOD mice expressing a murine
      beta(2)M(b) or human allele are protected. The murine beta(2)M(a) allele differs
      from the beta(2)M(b) allele only at a single amino acid. Mechanistic studies
      indicate that the absence of the NOD beta(2)M(a) isoform on nonhematopoietic
      cells inhibits the development or activation of diabetogenic T cells.

PMID- 11572997
TI  - Avicins, a family of triterpenoid saponins from Acacia victoriae (Bentham),
      suppress H-ras mutations and aneuploidy in a murine skin carcinogenesis model.
AB  - We tested the ability of avicins, a family of triterpenoid saponins obtained from
      Acacia victoriae (Bentham) (Leguminosae: Mimosoideae), to inhibit chemically
      induced mouse skin carcinogenesis. Varying doses of avicins were applied to
      shaved dorsal skin of SENCAR mice 15 min before application of 100 nmol of 7,12
      dimethylbenz[a]anthracene (DMBA) twice a week for 4 weeks (complete
      carcinogenesis model). The dorsal skin of a second group of mice was treated with
      one dose of 10 nmol of DMBA. Avicins were then applied 15 min before repetitive
      doses of 2 microg of phorbol 12-tetradecanoate 13-acetate (TPA) twice a week for
      8 weeks (initiation/promotion model). At 12 weeks, avicins produced a 70%
      decrease in the number of mice with papillomas and a greater than 90% reduction
      in the number of papillomas per mouse in both protocols. We also observed a 62%
      and 74% reduction by avicins in H-ras mutations at codon 61 in the DMBA and
      DMBA/TPA models, respectively, as well as a significant inhibition of the
      modified DNA base formation (8-OH-dG) in both protocols. Marked suppression of
      aneuploidy occurred with treatment at 16 weeks in the initiation/promotion
      experiment. These findings, when combined with the proapoptotic property of these
      compounds and their ability to inhibit hydrogen peroxide (H(2)O(2)) generation,
      nuclear factor-kappaB (NF-kappaB) activation, and inducible nitric oxide synthase
      (iNOS) induction reported elsewhere, suggest that avicins could prove exciting in
      reducing oxidative and nitrosative stress and thereby suppressing the development
      of human skin cancer and other epithelial malignancies.

PMID- 11572998
TI  - Avicins, a family of triterpenoid saponins from Acacia victoriae (Bentham),
      inhibit activation of nuclear factor-kappaB by inhibiting both its nuclear
      localization and ability to bind DNA.
AB  - Triterpenoid saponins, which are present in leguminous plants and some marine
      animals, possess a broad range of biological actions. We have earlier reported
      the extraction of avicins, a family of triterpenoid saponins obtained from the
      Australian desert tree Acacia victoriae (Leguminosae: Mimosoideae) that inhibit
      tumor cell growth and induce apoptosis, in part, by perturbing mitochondrial
      function. These saponins have also been found to prevent chemical-induced
      carcinogenesis in mice. This study examines the effect of a triterpene mixture
      (F094) and a single molecular species (avicin G) isolated from the mixture on
      tumor necrosis factor (TNF)-induced activation of nuclear transcription factor
      kappaB (NF-kappaB) in Jurkat cells (human T cell leukemia). Both F094 and avicin
      G were found to be potent inhibitors of TNF-induced NF-kappaB. Treatment of
      Jurkat cells with avicin G resulted in a much slower accumulation of the p65
      subunit of NF-kappaB into the nucleus whereas the degradation of IkappaBalpha was
      unaffected. Avicin G also impaired the binding of NF-kappaB to DNA in in vitro
      binding assays. Treatment of cells with DTT totally reversed the avicin G-induced
      inhibition of NF-kappaB activity, suggesting that sulfhydryl groups critical for
      NF-kappaB activation were being affected. Avicin G treatment resulted in
      decreased expression of NF-kappaB-regulated proteins such as inducible nitric
      oxide synthase (iNOS) and cyclooxygenase (COX-2). Thus, the avicins may prove
      important for reducing both oxidative and nitrosative cellular stress and thereby
      suppressing the development of malignancies and related diseases.

PMID- 11572999
TI  - Fruiting body formation by Bacillus subtilis.
AB  - Spore formation by the bacterium Bacillus subtilis has long been studied as a
      model for cellular differentiation, but predominantly as a single cell. When
      analyzed within the context of highly structured, surface-associated communities
      (biofilms), spore formation was discovered to have heretofore unsuspected spatial
      organization. Initially, motile cells differentiated into aligned chains of
      attached cells that eventually produced aerial structures, or fruiting bodies,
      that served as preferential sites for sporulation. Fruiting body formation
      depended on regulatory genes required early in sporulation and on genes evidently
      needed for exopolysaccharide and surfactin production. The formation of aerial
      structures was robust in natural isolates but not in laboratory strains, an
      indication that multicellularity has been lost during domestication of B.
      subtilis. Other microbial differentiation processes long thought to involve only
      single cells could display the spatial organization characteristic of
      multicellular organisms when studied with recent natural isolates.

PMID- 11573000
TI  - A universal protein-protein interaction motif in the eubacterial DNA replication
      and repair systems.
AB  - The interaction between DNA polymerases and sliding clamp proteins confers
      processivity in DNA synthesis. This interaction is critical for most DNA
      replication machines from viruses and prokaryotes to higher eukaryotes. The clamp
      proteins also participate in a variety of dynamic and competing protein-protein
      interactions. However, clamp-protein binding sequences have not so far been
      identified in the eubacteria. Here we show from three lines of evidence,
      bioinformatics, yeast two-hybrid analysis, and inhibition of protein-protein
      interaction by modified peptides, that variants of a pentapeptide motif
      (consensus QL[SD]LF) are sufficient to enable interaction of a number of proteins
      with an archetypal eubacterial sliding clamp (the beta subunit of Escherichia
      coli DNA polymerase III holoenzyme). Representatives of this motif are present in
      most sequenced members of the eubacterial DnaE, PolC, PolB, DinB, and UmuC
      families of DNA polymerases and the MutS1 mismatch repair protein family. The
      component tripeptide DLF inhibits the binding of the alpha (DnaE) subunit of E.
      coli DNA polymerase III to beta at microM concentration, identifying key
      residues. Comparison of the eubacterial, eukaryotic, and archaeal sliding clamp
      binding motifs suggests that the basic interactions have been conserved across
      the evolutionary landscape.

PMID- 11573001
TI  - Interference with Pseudomonas quinolone signal synthesis inhibits virulence
      factor expression by Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that controls numerous
      virulence factors through intercellular signals. This bacterium has two quorum
      sensing systems (las and rhl), which act through the intercellular signals N-(3
      oxododecanoyl)-l-homoserine lactone (3-oxo-C(12)-HSL) and N-butyryl-l-homoserine
      lactone (C(4)-HSL), respectively. P. aeruginosa also produces a third
      intercellular signal that is involved in virulence factor regulation. This
      signal, 2-heptyl-3-hydroxy-4-quinolone [referred to as the Pseudomonas quinolone
      signal (PQS)], is a secondary metabolite that is part of the P. aeruginosa quorum
      sensing hierarchy. PQS can induce both lasB (encodes LasB elastase) and rhlI
      (encodes the C(4)-HSL synthase) in P. aeruginosa and is produced maximally during
      the late stationary phase of growth. Because PQS is an intercellular signal that
      is part of the quorum-sensing hierarchy and controls multiple virulence factors,
      we began basic studies designed to elucidate its biosynthetic pathway. First, we
      present data that strongly suggest that anthranilate is a precursor for PQS. P.
      aeruginosa converted radiolabeled anthranilate into radioactive PQS, which was
      bioactive. We also found that an anthranilate analog (methyl anthranilate) would
      inhibit the production of PQS. This analog was then shown to have a major
      negative effect on elastase production by P. aeruginosa. These data provide
      evidence that precursors of intercellular signals may provide viable targets for
      the development of therapeutic treatments that will reduce P. aeruginosa
      virulence.

PMID- 11573002
TI  - Mapping adolescent brain change reveals dynamic wave of accelerated gray matter
      loss in very early-onset schizophrenia.
AB  - Neurodevelopmental models for the pathology of schizophrenia propose both
      polygenetic and environmental risks, as well as early (pre/perinatal) and late
      (usually adolescent) developmental brain abnormalities. With the use of brain
      mapping algorithms, we detected striking anatomical profiles of accelerated gray
      matter loss in very early-onset schizophrenia; surprisingly, deficits moved in a
      dynamic pattern, enveloping increasing amounts of cortex throughout adolescence.
      Early-onset patients were rescanned prospectively with MRI, at 2-year intervals
      at three time points, to uncover the dynamics and timing of disease progression
      during adolescence. The earliest deficits were found in parietal brain regions,
      supporting visuospatial and associative thinking, where adult deficits are known
      to be mediated by environmental (nongenetic) factors. Over 5 years, these
      deficits progressed anteriorly into temporal lobes, engulfing sensorimotor and
      dorsolateral prefrontal cortices, and frontal eye fields. These emerging patterns
      correlated with psychotic symptom severity and mirrored the neuromotor, auditory,
      visual search, and frontal executive impairments in the disease. In temporal
      regions, gray matter loss was completely absent early in the disease but became
      pervasive later. Only the latest changes included dorsolateral prefrontal cortex
      and superior temporal gyri, deficit regions found consistently in adult studies.
      These emerging dynamic patterns were (i) controlled for medication and IQ
      effects, (ii) replicated in independent groups of males and females, and (iii)
      charted in individuals and groups. The resulting mapping strategy reveals a
      shifting pattern of tissue loss in schizophrenia. Aspects of the anatomy and
      dynamics of disease are uncovered, in a changing profile that implicates genetic
      and nongenetic patterns of deficits.

PMID- 11573003
TI  - Initial recovery of vision after early monocular deprivation in kittens is faster
      when both eyes are open.
AB  - A comparison was made of the speed of visual recovery in the deprived eye of
      kittens after a 6-day period of monocular deprivation imposed at 5-9 weeks of age
      in two postdeprivation conditions. In one condition, binocular recovery (BR),
      both eyes were open, whereas in the other condition, reverse lid-suture (RLS),
      the formerly nondeprived eye was closed to force the animal to use the originally
      deprived eye. In littermate pairs, BR kittens began to recover form vision 12 to
      30 h before those subjected to RLS. The vision of the deprived eye of the BR
      animals remained superior to that of their RLS littermates for 4-8 days. Although
      this finding is difficult to reconcile with competitive mechanisms of synaptic
      plasticity, it supports a prediction of an alternative model of synaptic
      plasticity [Bienenstock, E. L., Cooper, L. N. & Munro, P. W. (1982) J. Neurosci.
      2, 32-48] for slower initial recovery with RLS because of the time required to
      reset the modification threshold.

PMID- 11573004
TI  - Posttranscriptional regulation of gene expression in learning by the neuronal
      ELAV-like mRNA-stabilizing proteins.
AB  - The view that memory is encoded by variations in the strength of synapses implies
      that long-term biochemical changes take place within subcellular microdomains of
      neurons. These changes are thought ultimately to be an effect of transcriptional
      regulation of specific genes. Localized changes, however, cannot be fully
      explained by a purely transcriptional control of gene expression. The neuron
      specific ELAV-like HuB, HuC, and HuD RNA-binding proteins act
      posttranscriptionally by binding to adenine- and uridine-rich elements (AREs) in
      the 3' untranslated region of a set of target mRNAs, and by increasing mRNA
      cytoplasmic stability and/or rate of translation. Here we show that neuronal ELAV
      like genes undergo a sustained up-regulation in hippocampal pyramidal cells only
      of mice and rats that have learned a spatial discrimination paradigm. This
      learning-specific increase of ELAV-like proteins was localized within cytoplasmic
      compartments of the somata and proximal dendrites and was associated with the
      cytoskeleton. This increase was also accompanied by enhanced expression of the
      GAP-43 gene, known to be regulated mainly posttranscriptionally and whose mRNA is
      demonstrated here to be an in vivo ELAV-like target. Antisense-mediated knockdown
      of HuC impaired spatial learning performance in mice and induced a concomitant
      down-regulation of GAP-43 expression. Neuronal ELAV-like proteins could exert
      learning-induced posttranscriptional control of an array of target genes uniquely
      suited to subserve substrates of memory storage.

PMID- 11573005
TI  - Conductivity tensor mapping of the human brain using diffusion tensor MRI.
AB  - Knowledge of the electrical conductivity properties of excitable tissues is
      essential for relating the electromagnetic fields generated by the tissue to the
      underlying electrophysiological currents. Efforts to characterize these
      endogenous currents from measurements of the associated electromagnetic fields
      would significantly benefit from the ability to measure the electrical
      conductivity properties of the tissue noninvasively. Here, using an effective
      medium approach, we show how the electrical conductivity tensor of tissue can be
      quantitatively inferred from the water self-diffusion tensor as measured by
      diffusion tensor magnetic resonance imaging. The effective medium model indicates
      a strong linear relationship between the conductivity and diffusion tensor
      eigenvalues (respectively, final sigma and d) in agreement with theoretical
      bounds and experimental measurements presented here (final sigma/d approximately
      0.844 +/- 0.0545 S small middle dots/mm(3), r(2) = 0.945). The extension to other
      biological transport phenomena is also discussed.

PMID- 11573006
TI  - Dehydroascorbic acid, a blood-brain barrier transportable form of vitamin C,
      mediates potent cerebroprotection in experimental stroke.
AB  - Neuronal injury in ischemic stroke is partly mediated by cytotoxic reactive
      oxygen species. Although the antioxidant ascorbic acid (AA) or vitamin C does not
      penetrate the blood-brain barrier (BBB), its oxidized form, dehydroascorbic acid
      (DHA), enters the brain by means of facilitative transport. We hypothesized that
      i.v. DHA would improve outcome after stroke because of its ability to cross the
      BBB and augment brain antioxidant levels. Reversible or permanent focal cerebral
      ischemia was created by intraluminal middle cerebral artery occlusion in mice
      treated with vehicle, AA, or DHA (40, 250, or 500 mg/kg), either before or after
      ischemia. Given before ischemia, DHA caused dose-dependent increases in
      postreperfusion cerebral blood flow, with reductions in neurological deficit and
      mortality. In reperfused cerebral ischemia, mean infarct volume was reduced from
      53% and 59% in vehicle- and AA-treated animals, respectively, to 15% in 250 mg/kg
      DHA-treated animals (P < 0.05). Similar significant reductions occurred in
      nonreperfused cerebral ischemia. Delayed postischemic DHA administration after 15
      min or 3 h also mediated improved outcomes. DHA (250 mg/kg or 500 mg/kg)
      administered at 3 h postischemia reduced infarct volume by 6- to 9-fold, to only
      5% with the highest DHA dose (P < 0.05). In contrast, AA had no effect on infarct
      volumes, mortality, or neurological deficits. No differences in the incidence of
      intracerebral hemorrhage occurred. Unlike exogenous AA, DHA confers in vivo, dose
      dependent neuroprotection in reperfused and nonreperfused cerebral ischemia at
      clinically relevant times. As a naturally occurring interconvertible form of AA
      with BBB permeability, DHA represents a promising pharmacological therapy for
      stroke based on its effects in this model of cerebral ischemia.

PMID- 11573007
TI  - Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates
      hippocampal long-term depression.
AB  - The interaction of PDZ domain-containing proteins with the C termini of alpha
      amino-3-hydroxy-5-methylisoxazolepropionate (AMPA) receptors has been suggested
      to be important in the regulation of receptor targeting to excitatory synapses.
      Recent studies have shown that the rapid internalization of AMPA receptors at
      synapses may mediate, at least in part, the expression of long-term depression
      (LTD). We have previously shown that phosphorylation of Ser-880 on the AMPA
      receptor GluR2 subunit differentially regulated the interaction of GluR2 with the
      PDZ domain-containing proteins GRIP1 and PICK1. Here, we show that induction of
      LTD in hippocampal slices increases phosphorylation of Ser-880 within the GluR2 C
      terminal PDZ ligand, suggesting that the modulation of GluR2 interaction with
      GRIP1 and PICK1 may regulate AMPA receptor internalization during LTD. Moreover,
      postsynaptic intracellular perfusion of GluR2 C-terminal peptides that disrupt
      GluR2 interaction with PICK1 inhibit the expression of hippocampal LTD. These
      results suggest that the interaction of GluR2 with PICK1 may play a regulatory
      role in the expression of LTD in the hippocampus.

PMID- 11573008
TI  - Molecular genetics and the evolution of ultraviolet vision in vertebrates.
AB  - Despite the biological importance of UV vision, its molecular bases are not well
      understood. Here, we present evidence that UV vision in vertebrates is determined
      by eight specific amino acids in the UV pigments. Amino acid sequence analyses
      show that contemporary UV pigments inherited their UV sensitivities from the
      vertebrate ancestor by retaining most of these eight amino acids. In the avian
      lineage, the ancestral pigment lost UV sensitivity, but some descendants regained
      it by one amino acid change. Our results also strongly support the hypothesis
      that UV pigments have an unprotonated Schiff base-linked chromophore.

PMID- 11573009
TI  - A zinc-sensing receptor triggers the release of intracellular Ca2+ and regulates
      ion transport.
AB  - Changes in extracellular zinc concentration participate in modulating fundamental
      cellular processes such as proliferation, secretion, and ion transport in a
      mechanism that is not well understood. Here, we show that a micromolar
      concentration of extracellular zinc triggers a massive release of calcium from
      thapsigargin-sensitive intracellular pools in the colonocytic cell line HT29.
      Calcium release was blocked by a phospholipase-C inhibitor, indicating that
      formation of inositol 1,4,5-triphosphate is required for zinc-dependent calcium
      release. Zinc influx was not observed, indicating that extracellular zinc
      triggered the release. The Ca(i)2+ release was zinc specific and could not be
      triggered by other heavy metals. Furthermore, zinc failed to activate the Ca(2+)
      sensing receptor heterologously expressed in HEK293 cells. The zinc-induced
      Ca(i)2+ rise stimulated the activity of the Na(+)/H(+) exchanger in HT29 cells.
      Our results indicate that a previously uncharacterized extracellular, G protein
      coupled, Zn(2+)-sensing receptor is functional in colonocytes. Because Ca(i)2+
      rise is known to regulate key cellular and signal-transduction processes, the
      zinc-sensing receptor may provide the missing link between extracellular zinc
      concentration changes and the regulation of cellular processes.

PMID- 11573010
TI  - Short-term exposure to pregnancy levels of estrogen prevents mammary
      carcinogenesis.
AB  - It is well established that pregnancy early in life reduces the risk of breast
      cancer in women and that this effect is universal. This phenomenon of parity
      protection against mammary cancer is also observed in rodents. Earlier studies
      have demonstrated that short-term administration of estradiol (E) in combination
      with progesterone mimics the protective effect of parity in rats. In this study,
      the lowest effective E dosage for preventing mammary cancer was determined. Rats
      were injected with N-methyl-N-nitrosourea at 7 weeks of age; 2 weeks later, the
      rats were subjected to sustained treatment with 20 microg, 100 microg, 200
      microg, or 30 mg of E in silastic capsules for 3 weeks. Treatments with 100
      microg, 200 microg, and 30 mg of E resulted in serum levels of E equivalent to
      those of pregnancy and were highly effective in preventing mammary cancer. E
      treatment (20 microg) did not result in pregnancy levels of E and was not
      effective in reducing the mammary cancer incidence. In another set of
      experiments, we determined the effect of different durations of E with or without
      progesterone treatments on mammary carcinogenesis. These experiments indicate
      that a period as short as one-third the period of gestation is sufficient to
      induce protection against mammary carcinogenesis. The pioneering aspect of our
      study in contrast to long-term estrogen exposure, which is thought to increase
      the risk of breast cancer, is that short-term sustained treatments with pregnancy
      levels of E can induce protection against frank mammary cancer.

PMID- 11573012
TI  - Auxin modulates the degradation rate of Aux/IAA proteins.
AB  - Aux/IAA gene family members were first identified by their rapid transcriptional
      increase in response to auxin. Auxin/indole-3-acetic acid protein (Aux/IAA)
      luciferase (LUC) fusions expressed in Arabidopsis under control of a non-auxin
      responsive promoter were used to monitor the effect of auxin on protein abundance
      independent of transcriptional regulation by auxin. After 2 hr in the presence of
      1 microM exogenous dichlorophenoxyacetic acid (2,4D), a synthetic auxin, the
      levels of pea IAA6 (PSIAA6) and Arabidopsis IAA1 LUC activity were 35% and 67%,
      respectively, of mock-treated genetically identical seedlings, whereas the
      activity of LUC alone from equivalently treated seedlings remained unaltered. The
      steady-state level of an Aux/IAA fusion protein lacking domain II, one of the
      conserved domains found in all Aux/IAA proteins, was not reduced in the presence
      of auxin. Higher levels of exogenous auxin were required to affect the steady
      state level of the PSIAA6LUC fusion with a point mutation in domain II. A 13-aa
      consensus sequence from domain II fused to LUC created an auxin-responsive fusion
      protein. The change in steady-state levels in response to auxin is extremely
      rapid, with a decrease in LUC activity detectable by 2 min after auxin
      application. Direct half-life measurements show that the decrease caused by
      exogenous auxin is due to the decrease in fusion protein half-life. These results
      suggest that auxin rapidly modulates the degradation rate of Aux/IAA proteins,
      with higher levels of auxin increasing the proteolytic rate of Aux/IAA family
      members.

PMID- 11573011
TI  - Modulation of nitric oxide bioavailability by erythrocytes.
AB  - Nitric oxide (NO) activates soluble guanylyl cyclase in smooth muscle cells to
      induce vasodilation in the vasculature. However, as hemoglobin (Hb) is an
      effective scavenger of NO and is present in high concentrations inside the red
      blood cell (RBC), the bioavailability of NO would be too low to elicit soluble
      guanylyl cyclase activation in the presence of blood. Therefore, NO bioactivity
      must be preserved. Here we present evidence suggesting that the RBC participates
      in the preservation of NO bioactivity by reducing NO influx. The NO uptake by
      RBCs was increased and decreased by altering the degree of band 3 binding to the
      cytoskeleton. Methemoglobin and denatured hemoglobin binding to the RBC membrane
      or cytoskeleton also were shown to contribute to reducing the NO uptake rate of
      the RBC. These alterations in NO uptake by the RBC, hence the NO bioavailability,
      were determined to correlate with the vasodilation of isolated blood vessels. Our
      observations suggest that RBC membrane and cytoskeleton associated NO-inert
      proteins provide a barrier for NO diffusion and thus account for the reduction in
      the NO uptake rate of RBCs.

PMID- 11573013
TI  - Spatiotemporal variation of metabolism in a plant circadian rhythm: the
      biological clock as an assembly of coupled individual oscillators.
AB  - The complex dynamic properties of biological timing in organisms remain a central
      enigma in biology despite the increasingly precise genetic characterization of
      oscillating units and their components. Although attempts to obtain the time
      constants from oscillations of gene activity and biochemical units have led to
      substantial progress, we are still far from a full molecular understanding of
      endogenous rhythmicity and the physiological manifestations of biological clocks.
      Applications of nonlinear dynamics have revolutionized thinking in physics and in
      biomedical and life sciences research, and spatiotemporal considerations are now
      advancing our understanding of development and rhythmicity. Here we show that the
      well known circadian rhythm of a metabolic cycle in a higher plant, namely the
      crassulacean acid metabolism mode of photosynthesis, is expressed as dynamic
      patterns of independently initiated variations in photosynthetic efficiency
      (phi(PSII)) over a single leaf. Noninvasive highly sensitive chlorophyll
      fluorescence imaging reveals randomly initiated patches of varying phi(PSII) that
      are propagated within minutes to hours in wave fronts, forming dynamically
      expanding and contracting clusters and clearly dephased regions of phi(PSII).
      Thus, this biological clock is a spatiotemporal product of many weakly coupled
      individual oscillators, defined by the metabolic constraints of crassulacean acid
      metabolism. The oscillators operate independently in space and time as a
      consequence of the dynamics of metabolic pools and limitations of CO(2) diffusion
      between tightly packed cells.

PMID- 11573014
TI  - LEAFY COTYLEDON2 encodes a B3 domain transcription factor that induces embryo
      development.
AB  - The Arabidopsis LEAFY COTYLEDON2 (LEC2) gene is a central embryonic regulator
      that serves critical roles both early and late during embryo development. LEC2 is
      required for the maintenance of suspensor morphology, specification of cotyledon
      identity, progression through the maturation phase, and suppression of premature
      germination. We cloned the LEC2 gene on the basis of its chromosomal position and
      showed that the predicted polypeptide contains a B3 domain, a DNA-binding motif
      unique to plants that is characteristic of several transcription factors. We
      showed that LEC2 RNA accumulates primarily during seed development, consistent
      with our finding that LEC2 shares greatest similarity with the B3 domain
      transcription factors that act primarily in developing seeds, VIVIPAROUS1/ABA
      INSENSITIVE3 and FUSCA3. Ectopic, postembryonic expression of LEC2 in transgenic
      plants induces the formation of somatic embryos and other organ-like structures
      and often confers embryonic characteristics to seedlings. Together, these results
      suggest that LEC2 is a transcriptional regulator that establishes a cellular
      environment sufficient to initiate embryo development.

PMID- 11573015
TI  - Intensely pleasurable responses to music correlate with activity in brain regions
      implicated in reward and emotion.
AB  - We used positron emission tomography to study neural mechanisms underlying
      intensely pleasant emotional responses to music. Cerebral blood flow changes were
      measured in response to subject-selected music that elicited the highly
      pleasurable experience of "shivers-down-the-spine" or "chills." Subjective
      reports of chills were accompanied by changes in heart rate, electromyogram, and
      respiration. As intensity of these chills increased, cerebral blood flow
      increases and decreases were observed in brain regions thought to be involved in
      reward/motivation, emotion, and arousal, including ventral striatum, midbrain,
      amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex. These brain
      structures are known to be active in response to other euphoria-inducing stimuli,
      such as food, sex, and drugs of abuse. This finding links music with biologically
      relevant, survival-related stimuli via their common recruitment of brain
      circuitry involved in pleasure and reward.

PMID- 11573016
TI  - Interoception: the inside story--a model for psychosomatic processes.
AB  - OBJECTIVE: To comprehend psychosomatic processes, it will be necessary to
      understand the brain's influences on bodily functions and also the body's
      afferent sensory input to the central nervous system, including the effects of
      this input on behavior and cognitive functions, especially emotion. The objective
      of this Presidential Address is to review what is known circa the year 2000 of
      the processes and mechanisms of visceral sensory psychobiology, often called
      interoception. METHODS: Over 1000 publications that have appeared since the 19th
      century were reviewed to prepare this review, including a group that are
      specifically cited here. RESULTS: Factors and data were reviewed that were
      identified as germane to understanding interoception. These included definitional
      issues, historical roots, the neural basis, studies and results in the
      cardiovascular-respiratory and alimentary-gastrointestinal systems, studies of
      emotion, and studies in people with mental disorders. Drug and hormone effects,
      pain, proprioception, and phantom limb or organ factors, and the role of
      awareness were briefly described. Methodological issues, methods of study
      including functional imaging, and possible future directions for study were
      identified. CONCLUSIONS: Understanding the physical basis of psychosomatic
      processes, including the so-called mind-body problem, will require a detailed
      understanding the psychobiology of interoception.

PMID- 11573017
TI  - Relationship of depressive symptoms to hypertension in a household survey in
      Harlem.
AB  - OBJECTIVE: Two possible explanations for an hypothesized association between
      depression and hypertension were examined: (1) shared stress-related risk factors
      are associated with both depression and hypertension and (2) life-style factors
      associated with depression lead to hypertension. METHODS: A predominantly black
      sample of 695 adults were interviewed in the Harlem Household Survey. Two
      measures of hypertension were used and compared-1) self-report and 2) elevated
      blood pressure (above 140/90 mm Hg)-on the basis of the mean of two blood
      pressure measures. Depressive symptoms were measured by use of a 24-item scale
      based on the Diagnostic Interview Schedule. Logistic regression models were used
      to test associations between hypertension and depressive symptoms, stressors, and
      life-style factors. RESULTS: Depressive symptoms were associated with self
      reported hypertension but not with elevated blood pressure. The association
      between self-reported hypertension and depressive symptoms was explained partly
      by shared stress-related risk factors but not by life-style factors. Several
      stressors and life-style variables were risk factors for elevated blood pressure
      independently of depressive symptoms. The findings are consistent with studies
      that have measured hypertension variously by either self-report or blood
      pressure. Possible explanations were explored (labeling and help-seeking) but
      were not supported by the data. CONCLUSIONS: An association was found between
      self-reported hypertension and depressive symptoms, which was explained partly by
      shared stress-related risk factors. Elevated blood pressure was associated with
      stressors and life-style factors but not with depressive symptomatology. Research
      on illness representations and cultural dimensions of health suggest avenues for
      further investigation.

PMID- 11573018
TI  - Socioeconomic differential in health and disease: let's take the next step.

PMID- 11573019
TI  - Employee effects of an educational program for managers at an insurance company.
AB  - BACKGROUND: Possible health effects for employees of efforts to improve the
      psychosocial competence of managers have not been studied scientifically in the
      past. OBJECTIVE: To explore how efforts to improve management will change the
      work environment and health of the employees. METHODS: Managers of the
      experimental department in a large insurance corporation underwent 2-hour
      biweekly training sessions for 1 year-altogether, 60 hours. A control group of
      employees in other departments in the corporation not affected by the
      modification was followed with the same assessments. Morning blood samples for
      the assessment of serum cortisol were collected both at baseline and after 1 year
      in 155 participants in the experimental group and in 147 subjects in the control
      group. Liver enzymes and lipids were also assessed. In the questionnaire part of
      the 1-year follow-up study, there were 119 participants in the experimental group
      and 132 in the control group. RESULTS: When repeated-measures ANOVA was used, a
      significant interaction effect was found for the level of serum cortisol; serum
      cortisol levels were decreased in the intervention group and were unchanged in
      the control group (ANOVA two-way interaction, p =.02; after exclusion of the
      managers, p =.005). A significant interaction effect was also observed for
      decision authority, with increased decision authority in the intervention group
      and, conversely, a decreased level in the control group (p =.001; after exclusion
      of managers, p =.02). CONCLUSIONS: The study indicates that a moderately
      intensive psychosocial manager program lasting for 1 year can be beneficial for
      the employees with regard to both lowered serum cortisol and improved authority
      over decisions.

PMID- 11573020
TI  - Job stress, control, and chronic disease: moving to the next level of evidence.

PMID- 11573021
TI  - Blood pressure reactions to acute psychological stress and future blood pressure
      status: a 10-year follow-up of men in the Whitehall II study.
AB  - OBJECTIVE: The aim of this study was to examine whether blood pressure reactions
      to mental stress predicted future blood pressure and hypertension. METHODS: Blood
      pressure was recorded at an initial medical screening examination after which
      blood pressure reactions to a mental stress task were determined. A follow-up
      screening assessment of blood pressure and antihypertensive medication status was
      undertaken 10 years later. Data were available for 796 male public servants,
      between 35 and 55 years of age upon entry to the study. RESULTS: Systolic blood
      pressure reactions to mental stress were positively correlated with follow-up
      screening systolic blood pressure and to a lesser extent, follow-up diastolic
      pressure. In multivariate tests, by far the strongest predictors of follow-up
      blood pressures were initial screening blood pressures. In the case of follow-up
      systolic blood pressure, systolic reactions to stress emerged as an additional
      predictor of follow-up systolic blood pressure. With regard to follow-up
      diastolic blood pressure, reactivity did not enter the analogous equations. The
      same outcomes emerged when the analyses were adjusted for medication status. When
      hypertension at 10-year follow-up was the focus, both systolic and diastolic
      reactions to stress were predictive. However, with correction for age and initial
      screening blood pressure, these associations were no longer statistically
      significant. CONCLUSIONS: The results of this study provide modest support for
      the hypothesis that heightened blood pressure reactions to mental stress
      contribute to the development of high blood pressure. At the same time, they
      question the clinical utility of stress testing as a prognostic device.

PMID- 11573022
TI  - Hypertension and the reactivity hypothesis: the next generation.

PMID- 11573024
TI  - Cardiovascular responses of women with chronic fatigue syndrome to stressful
      cognitive testing before and after strenuous exercise.
AB  - OBJECTIVE: The purpose of this study was to compare the cardiovascular responses
      of patients with chronic fatigue syndrome (CFS) to healthy control subjects when
      performing stressful cognitive tasks before and after strenuous exercise. METHOD:
      Beat-by-beat blood pressure and electrocardiogram were recorded on 19 women with
      CFS and 20 healthy nonexercising (ie, sedentary) women while they performed
      cognitive tests before, immediately after, and 24 hours after incremental
      exercise to exhaustion. RESULTS: Diminished heart rate (p <.01) and systolic (p
      <.01) and diastolic (p <.01) blood pressure responses to stressful cognitive
      testing were seen in patients with CFS when compared with healthy, sedentary
      controls. This diminished stress response was seen consistently in patients with
      CFS across three separate cognitive testing sessions. Also, significant negative
      correlations between self-ratings of CFS symptom severity and cardiovascular
      responses were seen (r = -0.62, p <.01). CONCLUSIONS: Women with CFS have a
      diminished cardiovascular response to cognitive stress; however, exercise did not
      magnify this effect. Also, the data showed that the patients with the lowest
      cardiovascular reactivity had the highest ratings of CFS symptom severity, which
      suggests that the individual response of the patient with CFS to stress plays a
      role in the common complaint of symptoms worsening after stress.

PMID- 11573023
TI  - Enhancing Recovery in Coronary Heart Disease (ENRICHD) study intervention:
      rationale and design.
AB  - OBJECTIVE: Depression and low social support are risk factors for medical
      morbidity and mortality after acute MI. The ENRICHD study is a multicenter,
      randomized, controlled clinical trial of a cognitive-behavioral treatment for
      depression and low social support in post-MI patients. A total of 2481 patients
      were recruited (26% with low social support, 39% with depression, and 34% with
      low social support and depression). Our objective is to describe the rationale,
      design, and delivery of the ENRICHD intervention. METHODS: Key features of the
      intervention include the integration of cognitive-behavioral and social learning
      approaches to the treatment of depression and a diverse set of problems that can
      contribute to low social support; rapid initiation of treatment after MI; a
      combination of individual and group modalities; adjunctive pharmacotherapy for
      severe or intractable depression; training, certification, and supervision of
      therapists; and quality assurance procedures. RESULTS: The trial's psychosocial
      and medical outcomes will be presented in future reports. CONCLUSIONS: The
      ENRICHD protocol targets two complex psychosocial risk factors with a
      multifaceted intervention, which is delivered in an individualized manner to
      accommodate a demographically, medically, and psychiatrically diverse patient
      population. Additional research will be needed to identify optimal matches
      between patient characteristics and specific components of the intervention.

PMID- 11573025
TI  - Gender differences in psychophysiological responses to speech stress among older
      social phobics:: congruence and incongruence between self-evaluative and
      cardiovascular reactions.
AB  - OBJECTIVE: Evidence suggests increased cardiovascular risk and autonomic
      impairment among individuals with chronic anxiety. Little attention, however, has
      been paid to the anxiety disorder of social phobia despite its high prevalence.
      Additionally, gender- and age-related cardiovascular profiles have not been
      examined in relation to social phobia. This study investigated cardiovascular
      responses to a socially threatening situation among older men and women with
      social phobia and control subjects. METHODS: Thirty subjects with social phobia
      and 30 control subjects (mean age = 65 years) were assessed during baseline,
      paced breathing, speech preparation, and speech presentation.
      Electrocardiographic variables, blood pressure, respiration, and emotional state
      (self-reported) were monitored. Hemodynamic variables included heart rate, blood
      pressure, cardiac output, and systemic vascular resistance; autonomic measures
      were respiratory sinus arrhythmia and baroreflex sensitivity, both markers of
      cardiac vagal control, and 0.10-Hz systolic blood pressure variability, an index
      of sympathetic vasomotor tone. RESULTS: Subjects with social phobia, in contrast
      to nonanxious control subjects, manifested more anxiety, embarrassment, and
      somatic complaints in response to stress; however, physiological measures
      generally did not distinguish groups. Interaction effects indicated that socially
      phobic women were hyperresponsive to the stressor with respect to self-reported,
      hemodynamic, and autonomic parameters. Socially phobic men manifested no
      physiological differences in comparison with control subjects, but they reported
      more psychological and somatic complaints. CONCLUSIONS: Gender differences in
      subjective and physiological responses to a socially threatening situation
      indicate congruence between perceived social anxiety and physiological responses
      in older women but not men. We found no evidence of impaired cardiovascular
      autonomic regulation among socially phobic men despite other reports that
      phobically anxious men are at greater cardiovascular risk.

PMID- 11573026
TI  - "Sleep is not tangible" or what the Hebrew tradition has to say about sleep.
AB  - Much of what is known about sleep disorders has been uncovered in the last forty
      years. As scientists, we consider these discoveries to be landmarks. Yet there is
      a tremendous amount of information written about sleep in the Bible and its
      commentaries. Sleep, and even sleep disorders, are referred to in many instances
      and can be directly interpreted by what we know today. Our forefathers and
      foremothers generally viewed sleep as both pleasant and necessary and were aware
      that sleep was not one continuous stage. They referred to the function of sleep
      as being restorative. They deplored sleep deprivation, believing that it impaired
      life. They felt that excessive sleepiness was harmful. They understood that
      insomnia could be caused by stress and anxiety and by excessive alcohol, and that
      physical activity (exercise) and drinking milk could improve sleep. They
      suggested cures for insomnia, including some of the ideas included in today's
      sleep hygiene rules. They understood that there was a rhythm or timing to sleep.
      They even understood that it is easier to delay the circadian rhythm that to
      advance it. Although naps are not recommended, they sometimes took naps in the
      afternoon, but suggested just how long that nap should last-about one-half hour.
      And they knew that with age, although sleep is advanced, healthy elderly do not
      have difficulty sleeping. Although we think we have discovered many new features
      about sleep disorders, much of what we know today was suggested thousands of
      years ago and documented in the Bible and the Talmud.

PMID- 11573028
TI  - Relation of type A behavior pattern and job-related psychosocial factors to
      nonfatal myocardial infarction: a case-control study of Japanese male workers and
      women.
AB  - OBJECTIVES: To study the relation of type A behavior pattern and job-related
      psychosocial factors to the risk of myocardial infarction. METHODS: Study
      subjects comprised 290 cases (173 male workers and 117 women) of nonfatal acute
      myocardial infarction (AMI) and 489 controls (303 male workers and 186 women)
      recruited from among residents of the study area. Participation rates of cases
      and controls were 86% and 50%, respectively. Type A behavior pattern, job-related
      psychosocial factors, and other coronary risk factors were ascertained by
      interview using a questionnaire. Type A behavior pattern was measured by 12
      questions, and job strain by the method of Karasek. Logistic regression analysis
      was used to calculate odds ratio and 95% confidence interval with adjustment for
      potential confounding variables. The relation to job strain was examined only in
      men. RESULTS: Type A behavior pattern was significantly associated with an
      increased risk of AMI in male workers (adjusted OR = 1.9, 95% CI, 1.2-2.9) and in
      women (adjusted OR = 2.8, 95% CI, 1.6-4.9). Although job control and job demand
      showed no material association with AMI, job strain, a combination of low job
      control and high job demand was associated with an increased risk of AMI
      (adjusted OR = 2.2, 95% CI, 1.1-4.5). Abbreviated type A score and job demand
      score were higher among nonparticipant control candidates than participant
      controls in male workers. CONCLUSIONS: Type A behavior pattern may be an
      important risk factor for AMI especially in Japanese women. The present study
      also revealed persons in stressful psychosocial circumstances were less likely to
      participate in the study.

PMID- 11573027
TI  - Cardiovascular indices of peripheral and central sympathetic activation.
AB  - OBJECTIVE: A number of sympathetic nervous system (SNS) parameters have been used
      in cardiovascular psychophysiology. This study aimed to describe the pattern and
      redundancy of a set of SNS parameters during peripherally induced changes of
      cardiac sympathetic activation and reflex modulation of central SNS control.
      Preejection period (PEP) was assessed as a marker of peripheral sympathetic
      activation. Low-frequency blood pressure variability (BPV) was assessed as an
      estimate of central SNS control. METHODS: Peripheral beta-sympathetic stimulation
      and blockade were achieved with epinephrine and esmolol hydrochloride (beta1
      blockade), respectively. Changes in central SNS output were induced by loading
      and unloading arterial baroreceptors with norepinephrine and nitroprusside
      sodium, respectively. This single-blinded, crossover study in 24 healthy men also
      included two placebo control periods. PEP was derived from impedance cardiography
      and adjusted individually for heart rate. BPV was calculated by power spectral
      analyses of beat-to-beat heart rate and systolic blood pressure (Finapres system)
      data. RESULTS: PEP decreased during epinephrine infusion (-40.1 +/- 3.8 ms, p
      <.0001) and increased during esmolol infusion (+6.6 +/- 3.5 ms, p =.05). PEP was
      shortened after central SNS activation by nitroprusside (-16.8 +/- 2.9 ms, p <
      0.0001). Systolic BPV in the low-frequency range (0.07-0.14 Hz, Mayer waves)
      increased during nitroprusside infusion (+0.44 +/- 0.19 ln mm Hg(2), p =.03) and
      decreased during norepinephrine infusion (-0.67 +/- 0.13 ln mm Hg(2), p <
      0.0001). Low-frequency BPV did not change significantly during epinephrine or
      esmolol infusion. CONCLUSIONS: Our data provide empirical evidence of separable
      peripheral and central sympathetic response components. The combined report of
      low-frequency BPV and PEP gives distinct information on both central SNS control
      and the level of sympathetic cardiac activation achieved.

PMID- 11573029
TI  - Psychological and physiological responses to postprandial mental stress in women
      with the irritable bowel syndrome.
AB  - OBJECTIVE: To investigate the psychological (affective and symptomatic) and
      physiological (autonomic and cortisol) responses to postprandial mental stress in
      women with irritable bowel syndrome (IBS). It was hypothesized that patients with
      IBS would show exaggerated autonomic and cortisol responses to the psychological
      stressor and that the stressor would enhance gastrointestinal symptoms. METHOD:
      Twenty-four women with IBS and 20 healthy women participated in the two-day study
      protocol. Both days were identical, with the exception that on one day, a
      stressful mental task was completed after ingestion of a standard meal. Heart
      rate variability, cortisol, affective, and symptomatic responses were measured
      before and after application of the stressor. RESULTS: Patients with IBS
      demonstrated increased negative affect at baseline and in response to the
      stressor. Gastrointestinal symptoms were not affected by the stressor. Appraisal
      of the stressor by patients with IBS was not different from that of controls.
      There were no group differences in the autonomic response to the stressor. There
      was no overall cortisol response to the stressor in either group. CONCLUSIONS:
      Patients with IBS respond with greater negative affect to postprandial
      psychological stress as well as to food intake alone, and they can be
      distinguished from controls on the basis of self-report data. Patients with IBS
      cannot be differentiated from controls on the basis of the pattern of changes in
      sympathetic activation after the mental stressor. The stressor used in this study
      did not elicit a cortisol response in either group.

PMID- 11573030
TI  - Responses to laboratory psychosocial stress in postpartum women.
AB  - OBJECTIVE: Lactation has been associated with attenuated hormonal responses to
      exercise stress in humans. This study was designed to determine the effect of
      lactation on hypothalamic-pituitary-adrenal axis, autonomic nervous system, and
      anxiety responses to psychological stress. METHOD: The Trier Social Stress Test
      was administered to 24 lactating women, 13 postpartum nonlactating women, and 14
      healthy control women in the early follicular phase of the menstrual cycle.
      Lactating women were stressed at least 40 minutes after last feeding their
      infant. RESULTS: ACTH, cortisol, heart rate, diastolic blood pressure, systolic
      blood pressure, and subjective anxiety ratings were all significantly increased
      in response to the psychological stress (all p <.0001). There were no differences
      among the three groups in any of these responses to the stress. However,
      postpartum nonlactating women did have a persistently higher systolic blood
      pressure and lower cardiac vagal tone than the lactating women and control
      subjects. In addition, the typical negative correlation between cardiac vagal
      tone and heart rate was consistently higher in lactating women than nonlactating
      postpartum women and controls, which suggests stronger vagal control of heart
      rate in lactating women. In addition, there was no change in oxytocin or
      allopregnanolone in response to the stress, and baseline oxytocin and
      allopregnanolone levels did not differ among the three groups. CONCLUSIONS: These
      results indicate that physiological and subjective responses to social stress are
      not attenuated in lactating women tested at least one hour after feeding their
      infant. However, enhanced vagal control of cardiac reactivity was observed in
      lactating women. In addition, postpartum women who did not lactate showed
      evidence of increased sympathetic and decreased parasympathetic nervous system
      tone.

PMID- 11573031
TI  - Changes in premenstrual symptoms in women with schizophrenia: a prospective
      study.
AB  - OBJECTIVE: We investigated whether the psychiatric symptoms and clinical features
      of schizophrenia change during the premenstrual phase in female patients.
      METHODS: We observed 30 female schizophrenic inpatients over one menstrual cycle.
      All subjects met DSM-IV criteria for schizophrenia, and all had a regular
      menstrual cycle. All subjects completed the Daily Rating Form (DRF) every
      evening, and one psychiatrist rated the subjects (using the Brief Psychiatric
      Rating Scale [BPRS]) once during each of the three menstrual phases
      (premenstrual, menstrual, and postmenstrual). Serum levels of estradiol (E2) and
      progesterone were measured on the fifth to seventh day of both the premenstrual
      and postmenstrual phases. Data from the 24 subjects who completed the DRF
      correctly and completely were used for statistical analysis. RESULTS: The mean
      total BPRS score for the 24 subjects was highest in the premenstrual phase and
      lowest in the postmenstrual phase, and a statistically significant difference was
      found among the three menstrual phases. Mean subtotal BPRS scores showed
      statistically significant differences among the three menstrual phases in
      anxiety/depression and withdrawal/retardation, but not in the psychotic symptom
      subscales. Mean serum E2 level showed a trend of increasing from the premenstrual
      phase to the postmenstrual phase. However, there was no significant correlation
      between DeltaBPRS and DeltaE2. When the criterion of 30% change was applied, the
      DRF items of depressed mood, anxious/nervous/restless, hostile/aggressive, and
      less/impaired work showed high frequencies of change in the premenstrual phase.
      Somatic items of abdominal pain, breast pain, and headache showed significant
      change with the 30% change rule on the DRF. On both the BPRS and DRF scores,
      premenstrual change of affective and behavioral symptoms was prominent, whereas
      the change of psychotic symptoms was minimal on the BPRS. In addition, in the
      premenstrual phase, there was a statistically significant correlation between the
      total BPRS score and the mean total DRF score. There was no correlation between
      premenstrual change in symptoms and hormonal levels of E2, progesterone, and the
      estradiol/progesterone (E/P) ratio. CONCLUSIONS: The findings of this study
      suggest that premenstrual exacerbation of schizophrenic symptoms in female
      patients may not be a worsening of the schizophrenic symptoms but a concurrence
      of affective, behavioral, and somatic symptoms.

PMID- 11573032
TI  - Antepartum depressive symptomatology is associated with adverse obstetric and
      neonatal outcomes.
AB  - OBJECTIVE: The purpose of this study was to examine if depressive symptomatology
      in pregnancy is associated with adverse obstetric and neonatal outcomes. METHOD:
      In a prospective observational study, 959 women were followed up longitudinally
      from early pregnancy to postpartum. The level of depression was measured at
      baseline (first antepartum visit) and in late pregnancy using the Beck Depression
      Inventory (BDI). Adverse obstetric and neonatal outcomes were recorded at
      delivery. RESULTS: Depression in late pregnancy was associated with increased
      risk of epidural analgesia (33% vs. 19%, p =.01, adjusted RR = 2.56, 95% CI 1.24
      5.30), operative deliveries (caesarean sections and instrumental vaginal
      deliveries) (39% vs. 27%, p =.02, adjusted RR = 2.28, 95% CI 1.15-4.53), and
      admission to neonatal care unit (24% vs. 19%, p =.03, adjusted RR = 2.18, 95% CI
      1.02-4.66). These effects remained significant even when controlled for potential
      confounders, such as antepartum complications. CONCLUSION: Previous studies have
      shown that antepartum anxiety or stress was associated with growth retardation,
      premature delivery, and epidural analgesia. Our findings add to this body of
      evidence, which together suggest an adverse impact of antepartum psychological
      morbidity on maternal and neonatal well-being.

PMID- 11573033
TI  - Posttraumatic stress disorder and the use of health services.
AB  - OBJECTIVE: Prior research has demonstrated increased use of medical services
      among persons with anxiety and depression. This investigation examined the
      possible association of posttraumatic stress disorder (PTSD) with the use of
      nonmental health services. METHOD: A case-comparison design enrolled 102 high
      users of health services and 54 low users who were assessed for PTSD diagnosis
      and severity of PTSD symptoms. Subjects were male veterans receiving services
      from the primary care clinics of the VA Boston Healthcare System during an 18
      month period. Data were collected by interview by use of standardized instruments
      including the Clinician Administered PTSD Scale for DSM-IV, the Life Events
      Checklist, and the Beck Depression Inventory. Data analysis employed odds ratios,
      linear and logistic regression, and path analyses. RESULTS: High users of health
      care were almost twice as likely as low users (27.5% vs. 14.8%) to meet
      diagnostic criteria for current PTSD. The two groups differed significantly on
      both symptom frequency and intensity. Path analyses showed an indirect positive
      association between PTSD and health services use, with physician-diagnosed health
      conditions as a mediating variable. Auxiliary analysis demonstrated that the
      combined mental health burden of PTSD and depression symptoms also is positively
      associated with number of health conditions. CONCLUSIONS: The findings indicate
      that PTSD, alone and in combination with depression, has a direct negative
      relationship with physical health that, in turn, is associated with more frequent
      use of primary health care services. These results do not suggest that PTSD leads
      to inappropriate (eg, distress-motivated) use of services.

PMID- 11573034
TI  - Posttraumatic stress symptomatology is associated with unexplained illness
      attributed to Persian Gulf War military service.
AB  - OBJECTIVE: Controversy exists concerning unexplained illness in Persian Gulf War
      veterans, especially regarding the contribution of psychological trauma. We
      sought to determine if war zone trauma or posttraumatic stress symptomatology
      (PTSS) are associated with illnesses reported by Gulf War veterans that were
      documented by medical examination but not attributable to a medical diagnosis.
      METHODS: A total of 1119 (55% response rate) of 2022 randomly sampled veterans of
      the United States Persian Gulf War were screened and 237 cases and 113 controls
      were identified by medical examination for a case-control study comparing Persian
      Gulf War military veterans with or without medically documented, but unexplained,
      symptoms. Multivariate logistic regression and cross-validation analyses examined
      self-report measures of demographics, subjective physical symptoms and
      functioning, psychiatric symptoms, stressors, war zone trauma, and PTSS, to
      identify correlates of case-control status. RESULTS: Posttraumatic stress
      symptomatology and somatic complaints were independently associated with case
      status, as were (although less consistently) war zone trauma and depression. Age,
      education, and self-reported health, stress-related somatization, pain,
      energy/fatigue, illness-related functional impairment, recent stressors, and
      anxiety were univariate (but not multivariate) correlates of case status.
      CONCLUSIONS: PTSS related to war zone trauma warrants additional prospective
      research study and attention in clinical screening and assessment as a potential
      contributor to the often debilitating physical health problems experienced by
      Persian Gulf War veterans.

PMID- 11573035
TI  - Self-efficacy as a predictor of adult adjustment to sickle cell disease: one-year
      outcomes.
AB  - OBJECTIVE: The present study prospectively investigated the role of self-efficacy
      in predicting disease symptomatology and health services utilization for adult
      patients with sickle cell disease. METHODS: These data are derived from a 12
      month prospective cohort study of African American adults with sickle cell
      disease. Disease-specific perceptions of coping self-efficacy and indices of
      disease severity, health care utilization, and psychosocial adjustment were
      assessed by use of standardized questionnaires administered by trained
      clinicians. RESULTS: Perceptions of self-efficacy for coping with sickle cell
      disease were moderately stable across the 12-month study period. At baseline (N =
      147), significant inverse relationships, measured with Pearson correlations, were
      noted between self-efficacy and the following variables: physical symptoms,
      psychological symptoms, pain severity, and number of physician visits over the
      preceding 12 months (p <.01). Similar relationships with self-efficacy were noted
      at the 1-year follow-up (N = 104) period for measures of physical symptoms,
      psychological symptoms, and pain severity (p <.01). In multiple-regression
      models, baseline self-efficacy scores predicted changes over the 1-year study
      period in physical and psychological sickle cell disease symptomatology.
      Moreover, changes in self-efficacy from baseline to 1-year follow-up were
      significantly and independently related to changes in physical symptoms,
      psychological symptoms, and pain ratings from baseline to 1-year follow-up.
      CONCLUSIONS: Self-efficacy beliefs among African American adults with sickle cell
      disease are inversely related to reported disease symptomatology, and these
      relationships persist across time. Future investigations should examine the
      mechanisms through which relationships between self-efficacy and adjustment to
      sickle cell disease are effected, as well as the feasibility and effectiveness of
      enhancing self-efficacy beliefs as a means of improving adjustment to sickle cell
      disease.

PMID- 11573036
TI  - Endoluminal graft repair for abdominal aortic aneurysms in high-risk patients and
      octogenarians: is it better than open repair?
AB  - OBJECTIVE: To analyze the short-term and midterm results of open and endoluminal
      repair of abdominal aortic aneurysms (AAA) in a large single-center series and
      specifically in octogenarians. METHODS: Between January 1997 and October 2000,
      470 consecutive patients underwent elective repair of AAA. Conventional open
      repair (COR) was performed in 210 patients and endoluminal graft (ELG) repair in
      260 patients. Ninety of the patients were 80 years of age or older; of these, 38
      underwent COR and 52 ELG repair. RESULTS: Patient characteristics and risk
      factors were similar for both the entire series and the subgroup of patients 80
      years or older. The overall complication rate was reduced by 70% or more in the
      ELG versus the COR groups. The postoperative death rate was similar for the COR
      and ELG groups in the entire series and lower (but not significantly) in the ELG
      80 years or older subgroup versus the COR group. The 36-month rates of freedom
      from endoleaks, surgical conversion, and secondary intervention were 81%, 98.2%,
      and 88%, respectively. CONCLUSION: The short-term and midterm results of AAA
      repair by COR or ELG are similar. The death rate associated with this new
      technique is low and comparable, whereas the complication rate associated with
      COR in all patients and those 80 years or older in particular is greater and more
      serious than ELG repair. Long-term results will establish the role of ELG repair
      of AAA, especially in elderly and high-risk patients.

PMID- 11573037
TI  - Carotid endarterectomy in women: challenging the results from ACAS and NASCET.
AB  - OBJECTIVE: To evaluate and compare the short- and long-term outcomes in female
      and male patients after carotid endarterectomy (CEA). SUMMARY BACKGROUND DATA:
      Randomized carotid trials have clearly shown the benefits of CEA in specific
      symptomatic and asymptomatic patients. However, the short- and long-term benefits
      in women appear to be less clear, and the role of CEA among women with carotid
      disease remains uncertain. METHODS: During a 21-year period, 1,204 CEAs were
      performed, 464 (39%) in women and 739 (61%) in men. Complete follow-up was
      available in 70% of patients. RESULTS: Women were less likely to have evidence of
      coronary artery disease, were more likely to be hypertensive, and had a
      significantly greater incidence of diabetes. The mean age at CEA was 68.5 +/- 9.5
      years for women and 68.0 +/- 8.5 years for men. There were no significant
      differences in the use of shunts, patching, tacking sutures, or severity of
      carotid stenoses between men and women. Surgical death rates were nearly
      identical for asymptomatic and symptomatic patients. Perioperative stroke rates
      were similar for asymptomatic and symptomatic patients. Life-table stroke-free
      rates at 1, 5, and 8 years were similar for asymptomatic women and men and
      symptomatic women and men. Long-term survival rates at 1, 5, and 8 years were
      higher for asymptomatic women compared with men and for symptomatic women
      compared with men. As a result, stroke-free survival rates at these follow-up
      intervals were greater for asymptomatic women compared with men, and for
      symptomatic women compared to men. CONCLUSIONS: The results from this study
      challenge the conclusions from the Asymptomatic Carotid Endarterectomy Study and
      the North American Symptomatic Carotid Endarterectomy Trial regarding the
      benefits of CEA in women. Female gender did not adversely affect early or late
      survival, stroke-free, or stroke-free death rates after CEA. The authors conclude
      that CEA can be performed safely in women with asymptomatic and symptomatic
      carotid artery disease, and physicians should expect comparable benefits and
      outcomes in women and men undergoing CEA.

PMID- 11573038
TI  - Midterm results of complete arterial revascularization in more than 1,000
      patients using an internal thoracic artery/radial artery T graft.
AB  - OBJECTIVE: To report the authors' 7-year experience with the internal thoracic
      artery/radial artery (ITA/RA) T graft as the only conduits for myocardial
      revascularization in two- and three-vessel disease. SUMMARY BACKGROUND DATA: One
      and two arterial conduits provide increasing survival benefit for coronary
      grafting and reduce the need for reintervention. Exclusive use of arterial
      conduits may provide further benefit. METHODS: From October 1993 to November
      2000, 1,020 patients underwent complete arterial revascularization with the
      ITA/RA T graft. The authors focus on the 909 having initial bypass, with a mean
      age of 60 and 20% age 70 or older. The incidence of triple-vessel disease was
      73%, female gender 28%, diabetes mellitus 27%, peripheral vascular disease 11%,
      cerebrovascular disease 10%, and chronic obstructive pulmonary disease 6%;
      ejection fraction was less than 35% in 11%. Perioperative data were collected
      prospectively. Follow-up information was obtained at a mean of 35.4 months (range
      1-88) and was 95% complete. RESULTS: There were seven (0.08%) deaths within 30
      days of surgery. The incidence of perioperative infarction was 3.3%, low cardiac
      output 2.7%, stroke 2.2%, reoperation for bleeding 3.8%, and deep sternal
      infection 0.8%. The actuarial survival rate was 90% at 5 years, freedom from
      infarction was 94%, freedom from catheterization was 83%, and freedom from
      reintervention (angioplasty or reoperation) was 93%. CONCLUSION: The ITA/RA T
      graft for complete arterial revascularization is associated with a low rate of
      perioperative death and complications and 5-year survival and freedom from
      reintervention values consistent with other revascularization strategies.

PMID- 11573039
TI  - Renal artery aneurysms: a 35-year clinical experience with 252 aneurysms in 168
      patients.
AB  - OBJECTIVE: To define the relevance of treating renal artery aneurysms (RAAs)
      surgically. SUMMARY BACKGROUND DATA: Most prior definitions of the clinical,
      pathologic, and management features of RAAs have evolved from anecdotal reports.
      Controversy surrounding this clinical entity continues. METHODS: A retrospective
      review was undertaken of 168 patients (107 women, 61 men) with 252 RAAs
      encountered over 35 years at the University of Michigan Hospital. Aneurysms were
      solitary in 115 patients and multiple in 53 patients. Bilateral RAAs occurred in
      32 patients. Associated diseases included hypertension (73%), renal artery
      fibrodysplasia (34%), systemic atherosclerosis (25%), and extrarenal aneurysms
      (6.5%). Most RAAs were saccular (79%) and noncalcified (63%). The main renal
      artery bifurcation was the most common site of aneurysms (60%). RAAs were often
      asymptomatic (55%), with a diagnosis made most often during arteriographic study
      for suspected renovascular hypertension (42%). RESULTS: Surgery was performed in
      121 patients (average RAA size 1.5 cm), including 14 patients undergoing
      unilateral repair with contralateral RAA observation. The remaining 47 patients
      (average RAA size 1.3 cm) were not treated surgically. Operations included
      aneurysmectomy and angioplastic renal artery closure or segmental renal artery
      reimplantation, aneurysmectomy and renal artery bypass, and planned nephrectomy
      for unreconstructable renal arteries or advanced parenchymal disease. Eight
      patients underwent unplanned nephrectomy, being considered a technical failure of
      surgical therapy. Dialysis-dependent renal failure occurred in one patient. There
      were no perioperative deaths. Late follow-up (average 91 months) was available in
      145 patients (86%). All but two arterial reconstructions remained clinically
      patent. Secondary renal artery procedures included percutaneous angioplasty,
      branch embolization, graft thrombectomy, and repeat bypass for late aneurysmal
      change of a vein conduit. Among 40 patients with clearly documented preoperative
      and postoperative blood pressure measurements, 60% had a significant decline in
      blood pressure after surgery while taking fewer antihypertensive medications.
      Late RAA rupture did not occur in the nonoperative patients, but no lessening of
      this group's hypertension was noted. CONCLUSION: Surgical therapy of RAAs in
      properly selected patients provides excellent long-term clinical outcomes and is
      often associated with decreased blood pressure.

PMID- 11573040
TI  - A decade's experience with quality improvement in cardiac surgery using the
      Veterans Affairs and Society of Thoracic Surgeons national databases.
AB  - OBJECTIVE: To review the Department of Veteran Affairs (VA) and the Society of
      Thoracic Surgeons (STS) national databases over the past 10 years to evaluate
      their relative similarities and differences, to appraise their use as quality
      improvement tools, and to assess their potential to facilitate improvements in
      quality of cardiac surgical care. SUMMARY BACKGROUND DATA: The VA developed a
      mandatory risk-adjusted database in 1987 to monitor outcomes of cardiac surgery
      at all VA medical centers. In 1989 the STS developed a voluntary risk-adjusted
      database to help members assess quality and outcomes in their individual programs
      and to facilitate improvements in quality of care. METHODS: A short data form on
      every veteran operated on at each VA medical center is completed and transmitted
      electronically for analysis of unadjusted and risk-adjusted death and
      complications, as well as length of stay. Masked, confidential semiannual reports
      are then distributed to each program's clinical team and the associated
      administrator. These reports are also reviewed by a national quality oversight
      committee. Thus, VA data are used both locally for quality improvement and at the
      national level with quality surveillance. The STS dataset (217 core fields and
      255 extended fields) is transmitted for each patient semiannually to the Duke
      Clinical Research Institute (DCRI) for warehousing, analysis, and distribution.
      Site-specific reports are produced with regional and national aggregate
      comparisons for unadjusted and adjusted surgical deaths and complications, as
      well as length of stay for coronary artery bypass grafting (CABG), valvular
      procedures, and valvular/CABG procedures. Both databases use the logistic
      regression modeling approach. Data for key processes of care are also captured in
      both databases. Research projects are frequently carried out using each database.
      RESULTS: More than 74,000 and 1.6 million cardiac surgical patients have been
      entered into the VA and STS databases, respectively. Risk factors that predict
      surgical death for CABG are very similar in the two databases, as are the odds
      ratios for most of the risk factors. One major difference is that the VA is 99%
      male, the STS 71% male. Both databases have shown a significant reduction in the
      risk-adjusted surgical death rate during the past decade despite the fact that
      patients have presented with an increased risk factor profile. The ratio of
      observed to expected deaths decreased from 1.05 to 0.9 for the VA and from 1.5 to
      0.9 for the STS. CONCLUSION: It appears that the routine feedback of risk
      adjusted data on local performance provided by these programs heightens awareness
      and leads to self-examination and self-assessment, which in turn improves quality
      and outcomes. This general quality improvement template should be considered for
      application in other settings beyond cardiac surgery.

PMID- 11573041
TI  - Robotic surgical training in an academic institution.
AB  - OBJECTIVE: To detail robotic procedure development and clinical applications for
      mitral valve, biliary, and gastric reflux operations, and to implement a
      multispecialty robotic surgery training curriculum for both surgeons and surgical
      teams. SUMMARY BACKGROUND DATA: Remote, accurate telemanipulation of
      intracavitary instruments by general and cardiac surgeons is now possible.
      Complex technologic advancements in surgical robotics require well-designed
      training programs. Moreover, efficient robotic surgical procedures must be
      developed methodically and safely implemented clinically. METHODS: Advanced
      training on robotic systems provides surgeon confidence when operating in tiny
      intracavitary spaces. Three-dimensional vision and articulated instrument control
      are essential. The authors' two da Vinci robotic systems have been dedicated to
      procedure development, clinical surgery, and training of surgical specialists.
      Their center has been the first United States site to train surgeons formally in
      clinical robotics. RESULTS: Established surgeons and residents have been trained
      using a defined robotic surgical educational curriculum. Also, 30 multispecialty
      teams have been trained in robotic mechanics and electronics. Initially, robotic
      procedures were developed experimentally and are described. In the past year the
      authors have performed 52 robotic-assisted clinical operations: 18 mitral valve
      repairs, 20 cholecystectomies, and 14 Nissen fundoplications. These respective
      operations required 108, 28, and 73 minutes of robotic telemanipulation to
      complete. Procedure times for the last half of the abdominal operations decreased
      significantly, as did the knot-tying time in mitral operations. There have been
      no deaths and few complications. One mitral patient had postoperative bleeding.
      CONCLUSION: Robotic surgery can be performed safely with excellent results. The
      authors have developed an effective curriculum for training teams in robotic
      surgery. After training, surgeons have applied these methods effectively and
      safely.

PMID- 11573042
TI  - Prospective randomized clinical trial of the value of intraperitoneal drainage
      after pancreatic resection.
AB  - OBJECTIVE: To test the hypothesis that routine intraperitoneal drainage is not
      required after pancreatic resection. SUMMARY BACKGROUND DATA: The use of
      surgically placed intraperitoneal drains has been considered routine after
      pancreatic resection. Recent studies have suggested that for other major upper
      abdominal resections, routine postoperative drainage is not required and may be
      associated with an increased complication rate. METHODS: After informed consent,
      eligible patients with peripancreatic tumors were randomized during surgery
      either to have no drains placed or to have closed suction drainage placed in a
      standardized fashion after pancreatic resection. Clinical, pathologic, and
      surgical details were recorded. RESULTS: One hundred seventy-nine patients were
      enrolled in the study, 90 women and 89 men. Mean age was 65.4 years (range 23
      87). The pancreas was the tumor site in 142 (79%) patients, with the ampulla (n =
      24), duodenum (n = 10), and distal common bile duct (n = 3) accounting for the
      remainder. A pancreaticoduodenectomy was performed in 139 patients and a distal
      pancreatectomy in 40 cases. Eighty-eight patients were randomized to have drains
      placed. Demographic, surgical, and pathologic details were similar between both
      groups. The overall 30-day death rate was 2% (n = 4). A postoperative
      complication occurred during the initial admission in 107 patients (59%). There
      was no significant difference in the number or type of complications between
      groups. In the drained group, 11 patients (12.5%) developed a pancreatic fistula.
      Patients with a drain were more likely to develop a significant intraabdominal
      abscess, collection, or fistula. CONCLUSION: This randomized prospective clinical
      trial failed to show a reduction in the number of deaths or complications with
      the addition of surgical intraperitoneal closed suction drainage after pancreatic
      resection. The data suggest that the presence of drains failed to reduce either
      the need for interventional radiologic drainage or surgical exploration for
      intraabdominal sepsis. Based on these results, closed suction drainage should not
      be considered mandatory or standard after pancreatic resection.

PMID- 11573043
TI  - Comparison of surgical results in patients with advanced and limited disease with
      multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome.
AB  - OBJECTIVE: To determine the role of surgery in patients with Zollinger-Ellison
      syndrome (ZES) and multiple endocrine neoplasia type 1 (MEN1) with either limited
      or advanced pancreatic endocrine tumors (PETs). SUMMARY BACKGROUND DATA: The role
      of surgery in patients with MEN1 and ZES is controversial. There have been
      numerous previous studies of surgery in patients with PETs; however, there are no
      prospective studies on the results of surgery in patients with advanced disease.
      METHODS: Eighty-one consecutive patients with MEN1 and ZES were assigned to one
      of four groups depending on the results of imaging studies. Group 1 (n = 17) (all
      PETs smaller than 2.5 cm) and group 3 (n = 8) (diffuse liver metastases) did not
      undergo surgery. All patients in group 2A (n = 17; single PET 2.5-6 cm [limited
      disease]) and group 2B (n = 31; two or more lesions, 2.5 cm in diameter or
      larger, or one lesion larger than 6 cm) underwent laparotomy. Tumors were
      preferably removed by simple enucleation, or if not feasible resection. Patients
      were reevaluated yearly. RESULTS: Pancreatic endocrine tumors were found in all
      patients at surgery, with groups 2A and 2B having 1.7 +/- 0.4 and 4.8 +/- 1 PETs,
      respectively. Further, 35% of the patients in group 2A and 88% of the patients in
      group 2B had multiple PETs, 53% and 84% had a pancreatic PET, 53% and 68% had a
      duodenal gastrinoma, 65% and 71% had lymph node metastases, and 0% and 12% had
      liver metastases. Of the patients in groups 2A and 2B, 24% and 58% had a distal
      pancreatectomy, 0% and 13% had a hepatic resection, 0% and 6% had a Whipple
      operation, and 53% and 68% had a duodenal resection. No patient was cured at 5
      years. There were no deaths. The early complication rate, 29%, was similar for
      groups 2A and 2B. Mean follow-up from surgery was 6.9 +/- 0.8 years, and during
      follow-up liver metastases developed in 6% of the patients in groups 2A and 2B.
      Groups 1, 2A, and 2B had similar 15-year survival rates (89-100%); they were
      significantly better than the survival rate for group 3 (52%). CONCLUSIONS:
      Almost 40% of patients with MEN1 and ZES have advanced disease without diffuse
      distant metastases. Despite multiple primaries and a 70% incidence of lymph node
      metastases, tumor can be removed with no deaths and complication rates similar to
      those in patients with limited disease. Further, despite previous studies showing
      that patients with advanced disease have decreased survival rates, in this study
      the patients with advanced tumor who underwent surgical resection had the same
      survival as patients with limited disease and patients without identifiable
      tumor. This suggests that surgical resection should be performed in patients with
      MEN1 who have ZES and advanced localized PET.

PMID- 11573044
TI  - Staging, resectability, and outcome in 225 patients with hilar
      cholangiocarcinoma.
AB  - OBJECTIVE: To analyze resectability and survival in patients with hilar
      cholangiocarcinoma according to a proposed preoperative staging scheme that fully
      integrates local, tumor-related factors. SUMMARY BACKGROUND DATA: In patients
      with hilar cholangiocarcinoma, long-term survival depends critically on complete
      tumor resection. The current staging systems ignore factors related to local
      tumor extent, preclude accurate preoperative disease assessment, and correlate
      poorly with resectability and survival. METHODS: Demographics, results of imaging
      studies, surgical findings, pathology, and survival were analyzed prospectively
      in consecutive patients. Using data from imaging studies, all patients were
      placed into one of three stages based on the extent of ductal involvement by
      tumor, the presence or absence of portal vein compromise, and the presence or
      absence of hepatic lobar atrophy. RESULTS: From March 1991 through December 2000,
      225 patients were evaluated, 77% of whom were seen and treated within the last 6
      years. Sixty-five patients had unresectable disease; 160 patients underwent
      exploration with curative intent. Eighty patients underwent resection: 62 (78%)
      had a concomitant hepatic resection and 62 (78%) had an R0 resection (negative
      histologic margins). Negative histologic margins, concomitant partial
      hepatectomy, and well-differentiated tumor histology were associated with
      improved outcome after all resections. However, in patients who underwent an R0
      resection, concomitant partial hepatectomy was the only independent predictor of
      long-term survival. Of the 9 actual 5-year survivors (of 30 at risk), all had a
      concomitant hepatic resection and none had tumor-involved margins; 3 of these 9
      patients remained free of disease at a median follow-up of 88 months. The rates
      of complications and death after resection were 64% and 10%, respectively. In the
      219 patients whose disease could be staged, the proposed system predicted
      resectability and the likelihood of an R0 resection and correlated with
      metastatic disease and survival. CONCLUSION: By taking full account of local
      tumor extent, the proposed staging system for hilar cholangiocarcinoma accurately
      predicts resectability, the likelihood of metastatic disease, and survival.
      Complete resection remains the only therapy that offers the possibility of long
      term survival, and hepatic resection is a critical component of the surgical
      approach.

PMID- 11573045
TI  - Curative resection for esophageal adenocarcinoma: analysis of 100 en bloc
      esophagectomies.
AB  - OBJECTIVE: To document what can be accomplished with surgical resection done
      according to the classical principles of surgical oncology. METHODS: One hundred
      consecutive patients underwent en bloc esophagectomy for esophageal
      adenocarcinoma. No patient received pre- or postoperative chemotherapy or
      radiation therapy. Tumor depth and number and location of involved lymph nodes
      were recorded. A lymph node ratio was calculated by dividing the number of
      involved nodes by the total number removed. Follow-up was complete in all
      patients. The median follow-up of surviving patients was 40 months, with 23
      patients surviving 5 years or more. RESULTS: The overall actuarial survival rate
      at 5 years was 52%. Survival rates by American Joint Commission on Cancer (AJCC)
      stage were stage 1 (n = 26), 94%; stage 2a (n = 11), 65%; stage 2b (n = 13), 65%;
      stage 3 (n = 32), 23%; and stage 4 (n = 18), 27%. Sixteen tumors were confined to
      the mucosa, 16 to the submucosa, and 13 to the muscularis propria, and 55 were
      transmural. Tumor depth and the number and ratio of involved nodes were
      predictors of survival. Metastases to celiac (n = 16) or other distant node sites
      (n = 26) were not associated with decreased survival. Local recurrence was seen
      in only one patient. Latent nodal recurrence outside the surgical field occurred
      in 9 patients and systemic metastases in 31. Tumor depth, the number of involved
      nodes, and the lymph node ratio were important predictors of systemic recurrence.
      The surgical death rate was 6%. CONCLUSION: Long-term survival from
      adenocarcinoma of the esophagus can be achieved in more than half the patients
      who undergo en bloc resection. One third of patients with lymph node involvement
      survived 5 years. Local control is excellent after en bloc resection. The extent
      of disease associated with tumors confined to the mucosa and submucosa provides
      justification for more limited and less morbid resections.

PMID- 11573046
TI  - Long-term outcome of antireflux surgery in patients with Barrett's esophagus.
AB  - OBJECTIVE: To assess the long-term outcome of antireflux surgery in patients with
      Barrett's esophagus. SUMMARY BACKGROUND DATA: The prevalence of Barrett's
      esophagus is increasing, and its treatment is problematic. Antireflux surgery has
      the potential to stop reflux and induce a quiescent mucosa. Its long-term
      outcome, however, has recently been challenged with reports of poor control of
      reflux and the inability to prevent progression to cancer. METHODS: The outcome
      of antireflux surgery was studied in 97 patients with Barrett's esophagus. Follow
      up was complete in 88% (85/97) at a median of 5 years. Fifty-nine had long
      segment and 26 short-segment Barrett's. Patients with intestinal metaplasia of
      the cardia were excluded. Fifty patients underwent a laparoscopic procedure, 20 a
      transthoracic procedure, and 3 abdominal Nissen operations. Nine had a Collis
      Belsey procedure and three had other partial wraps. Outcome measures included
      relief of reflux symptoms (all), patients' perception of the result (all), upper
      endoscopy and histology (n = 79), and postoperative 24-hour pH monitoring (n =
      21). RESULTS: At a median follow-up of 5 years, reflux symptoms were absent in 67
      of 85 patients (79%). Eighteen (20%) developed recurrent symptoms; four had
      returned to taking daily acid-suppression medication. Seven patients underwent a
      secondary repair and were asymptomatic, increasing the eventual successful
      outcome to 87%. Recurrent symptoms were most common in patients undergoing Collis
      Belsey (33%) and laparoscopic Nissen (26%) procedures and least common after a
      transthoracic Nissen operation (5%). The results of postoperative 24-hour pH
      monitoring were normal in 17 of 21 (81%). Recurrent hiatal hernias were detected
      in 17 of 79 patients studied; 6 were asymptomatic. Seventy-seven percent of the
      patients considered themselves cured, 22% considered their condition to be
      improved, and 97% were satisfied. Low-grade dysplasia regressed to nondysplastic
      Barrett's in 7 of 16 (44%), and intestinal metaplasia regressed to cardiac mucosa
      in 9 of 63 (14%). Low-grade dysplasia developed in 4 of 63 (6%) patients. No
      patient developed high-grade dysplasia or cancer in 410 patient-years of follow
      up. CONCLUSIONS: After antireflux surgery, most patients with Barrett's enjoy
      long-lasting relief of reflux symptoms, and nearly all patients consider
      themselves cured or improved. Mild symptoms recur in one fifth. Importantly,
      dysplasia regressed in nearly half of the patients in whom it was present before
      surgery, intestinal metaplasia disappeared in 14% of patients, and high-grade
      dysplasia and adenocarcinoma were prevented in all.

PMID- 11573047
TI  - Results of hepatic resection for sarcoma metastatic to liver.
AB  - OBJECTIVE: To evaluate the outcome of patients with liver metastases from sarcoma
      who underwent hepatic resection at a single institution and were followed up
      prospectively. SUMMARY BACKGROUND DATA: The value of hepatic resection for
      metastatic sarcoma is unknown. METHODS: There were 331 patients with liver
      metastases from sarcoma who were admitted to Memorial Hospital from 1982 to 2000,
      and 56 of them underwent resection of all gross hepatic disease. Patient, tumor,
      and treatment variables were analyzed to assess outcome. RESULTS: Of the 56
      patients who underwent complete resection, 34 (61%) had gastrointestinal stromal
      tumors or gastrointestinal leiomyosarcomas. Half of the patients required an
      hepatic lobectomy or extended lobectomy. There were no perioperative deaths in
      the completely resected group, although 3 of the 75 patients who underwent
      exploration (4%) died. The postoperative 1-, 3-, and 5-year actuarial survival
      rates were 88%, 50%, and 30%, respectively, with a median of 39 months. In
      contrast, the 5-year survival rate of patients who did not undergo complete
      resection was 4%. On multivariate analysis, a time interval from the primary
      tumor to the development of liver metastasis greater than 2 years was a
      significant predictor of survival after hepatectomy. CONCLUSIONS: Complete
      resection of liver metastases from sarcoma in selected patients is associated
      with prolonged survival. Hepatectomy should be considered when complete gross
      resection is possible, especially when the time to the development of liver
      metastasis exceeds 2 years.

PMID- 11573048
TI  - Bile duct injury during laparoscopic cholecystectomy: results of a national
      survey.
AB  - OBJECTIVE: To determine whether surgical residency training has influenced the
      occurrence of common bile duct injuries during laparoscopic cholecystectomy, and
      to asses the anatomic and technical details of bile duct injuries from the
      practices of surgeons trained in laparoscopic cholecystectomy after residency
      versus surgeons trained in laparoscopic cholecystectomy during residency. SUMMARY
      BACKGROUND DATA: Shortly after the introduction of laparoscopic cholecystectomy,
      the rate of injury to the common bile duct increased to 0.5%, and injuries were
      more commonly reported early in each surgeon's experience. It is not known
      whether learning laparoscopic cholecystectomy during surgery residency influences
      this pattern. METHODS: An anonymous questionnaire was mailed to 3,657 surgeons
      across the United States who completed an Accreditation Council for Graduate
      Medical Education (ACGME)-approved residency between 1980 and 1990 (group A) or
      1992 and 1998 (group B). All surgeons in group A learned laparoscopic
      cholecystectomy after residency, and all those in group B learned laparoscopic
      cholecystectomy during residency. Information obtained included practice
      description, number of laparoscopic cholecystectomies completed since residency,
      postgraduate training in laparoscopy, and annual volume of laparoscopic
      cholecystectomy in the surgeon's hospital. In addition, technical details queried
      included the completion of a cholangiogram, the interval between injury and
      identification, the method of repair, and the site of definitive treatment. The
      primary endpoint was the occurrence of a major bile duct injury during
      laparoscopic cholecystectomy (bile leaks without a major bile duct injury were
      not tabulated). RESULTS: Forty-five percent (n = 1,661) of the questionnaires
      were completed and returned. Mean practice experience was 13.6 years for group A
      and 5.4 years for group B. At least one injury occurrence was reported by 422
      surgeons (37.6%) in group A and 143 surgeons (26.5%) in group B. Forty percent of
      the injuries in group A occurred during the first 50 cases compared with 22% in
      group B. Thirty percent of bile duct injuries in group A and 32.9% of all
      injuries in group B occurred after a surgeon had performed more than 200
      laparoscopic cholecystectomies. Independent of the number of laparoscopic
      cholecystectomies completed since residency, group A surgeons were 39% more
      likely to report one or more biliary injuries and 58% more likely to report two
      or more injuries than their counterparts in group B. Bile duct injuries were more
      likely to be discovered during surgery if a cholangiogram was completed than if
      cholangiography was omitted (80.9% vs. 45.1%). Sixty-four percent of all major
      bile duct injuries required biliary reconstruction, and most injuries were
      definitively treated at the hospital where the injury occurred. Only 14.7% of
      injuries were referred to another center for repair. CONCLUSIONS: Accepting that
      the survey bias underestimates the true frequency of bile duct injuries,
      residency training decreases the likelihood of injuring a bile duct, but only by
      decreasing the frequency of early "learning curve" injuries. If one accepts a
      liberal definition of the learning curve (200 cases), it appears that at least
      one third of injuries are not related to inexperience but may reflect fundamental
      errors in the technique of laparoscopic cholecystectomy as practiced by a broad
      population of surgeons in the United States. Intraoperative cholangiography is
      helpful for intraoperative discovery of injuries when they occur. Most injuries
      are repaired in the hospital where they occur and are not universally referred to
      tertiary care centers.

PMID- 11573049
TI  - Effect of epidural anesthesia and analgesia on perioperative outcome: a
      randomized, controlled Veterans Affairs cooperative study.
AB  - OBJECTIVE: To test the hypothesis that epidural anesthesia and postoperative
      epidural analgesia decrease the incidence of death and major complications during
      and after four types of intraabdominal surgical procedures. SUMMARY BACKGROUND
      DATA: Even though many beneficial aspects of epidural anesthesia have been
      reported, clinical trials of epidural anesthesia for outcome of surgical patients
      have shown conflicting results. METHODS: The authors studied 1,021 patients who
      required anesthesia for one of the intraabdominal aortic, gastric, biliary, or
      colon operations. They were assigned randomly to receive either general
      anesthesia and postoperative analgesia with parenteral opioids (group 1) or
      epidural plus light general anesthesia and postoperative epidural morphine (group
      2). The patients were monitored for death and major complications during and for
      30 days after surgery, as well as for postoperative pain, time of ambulation, and
      length of hospital stay. RESULTS: Overall, there was no significant difference in
      the incidence of death and major complications between the two groups. For
      abdominal aortic surgical patients, unlike the other three types of surgical
      patients, the overall incidence of death and major complications was
      significantly lower in group 2 patients (22%) than in group 1 patients (37%),
      stemming from differences in the incidence of new myocardial infarction, stroke,
      and respiratory failure between the two groups. Overall, group 2 patients
      received significantly less analgesic medication but had better pain relief than
      group 1 patients. In group 2 aortic patients, endotracheal intubation time was 13
      hours shorter and surgical intensive care stay was 3.5 hours shorter.
      CONCLUSIONS: The effect of anesthetic and postoperative analgesic techniques on
      perioperative outcome varies with the type of operation performed. Overall,
      epidural analgesia provides better postoperative pain relief. Epidural anesthesia
      and epidural analgesia improve the overall outcome and shorten the intubation
      time and intensive care stay in patients undergoing abdominal aortic operations.

PMID- 11573050
TI  - Necrotizing pancreatitis: contemporary analysis of 99 consecutive cases.
AB  - OBJECTIVE: To analyze the impact of a conservative strategy of management in
      patients with necrotizing pancreatitis, reserving intervention for patients with
      documented infection or the late complications of organized necrosis. SUMMARY
      BACKGROUND DATA: The role of surgery in patients with sterile pancreatic necrosis
      remains controversial. Although a conservative approach is being increasingly
      used, few studies have evaluated this strategy when applied to the entire
      spectrum of patients with necrotizing pancreatitis. METHODS: The authors reviewed
      1,110 consecutive patients with acute pancreatitis managed at Brigham and Women's
      Hospital between January 1, 1995, and January 1, 2000, focusing on those with
      pancreatic necrosis documented by contrast-enhanced computed tomography. Fine
      needle aspiration, the presence of extraintestinal gas on computed tomography, or
      both were used to identify infection. RESULTS: There were 99 (9%) patients with
      necrotizing pancreatitis treated, with an overall death rate of 14%. In three
      patients with underlying medical problems, the decision was made initially not to
      intervene. Of the other 62 patients without documented infection, all but 3 were
      managed conservatively; this group's death rate was 11%. Of these seven deaths,
      all were related to multiorgan failure. Five patients in this group eventually
      required surgery for organized necrosis, with no deaths. Of the 34 patients with
      infected necrosis, 31 underwent surgery and 3 underwent percutaneous drainage.
      Only four (12%) of these patients died, all of multiorgan failure. Of the total
      11 patients who died, few if any would have been candidates for earlier surgical
      intervention. CONCLUSIONS: These results suggest that conservative strategies can
      be applied successfully to manage most patients with necrotizing pancreatitis,
      although some will eventually require surgery for symptomatic organized necrosis.
      Few if any patients seem likely to benefit from a more aggressive strategy.

PMID- 11573051
TI  - The muscle flow/performance dissociation phenomenon.

PMID- 11573052
TI  - Fibrinogen, lipoprotein (a) and lipids in patients with erectile dysfunction. A
      preliminary study.
AB  - BACKGROUND: Erectile dysfunction is associated with cardiovascular risk factors
      (e.g. hypertension, smoking, dyslipidemia and diabetes) and is more common in
      patients with cardiovascular disease. We therefore assessed the prevalence of two
      predictors of vascular events, fibrinogen and lipoprotein-a, in patients with and
      without erectile dysfunction. METHODS: Men with erectile dysfunction (48 non
      smokers, 48 smokers), aged 45-70 years, were compared with controls (21 non
      smokers, 21 smokers) with normal erectile function and no known pathology.
      RESULTS: Serum total cholesterol was significantly higher in non-smokers with
      erectile dysfunction compared to both control non-smokers and erectile
      dysfunction smokers. Men with erectile dysfunction who smoked had a significantly
      higher plasma fibrinogen level than control smokers. Similarly, men with erectile
      dysfunction, who did not smoke had higher levels of plasma fibrinogen compared to
      both smokers and non-smokers without erectile dysfunction. No significant
      difference in serum lipoprotein-a values was found. CONCLUSIONS: These findings
      support the concept that cardiovascular risk factors are predictors of erectile
      dysfunction and that this may be another manifestation of vascular disease.

PMID- 11573053
TI  - Impact of atherosclerotic risk factors on the anatomical distribution of
      peripheral arterial disease.
AB  - BACKGROUND: The aim of the study was to determine predictors of hemodynamically
      relevant atherosclerosis (HRA) in different segments of lower limb arteries in
      patients with peripheral arterial disease (PAD). METHODS: In a retrospective case
      control study 106 hospitalized consecutive patients with symptomatic PAD and 52
      asymptomatic control subjects were studied. All patients underwent distal
      aortofemoral angiography. The arteries of the lower limbs were divided into three
      sections: in the aorto-iliac and femoro-popliteal segments HRA was defined as one
      or more stenosis of over 50%. In the crural segment it was considered if at least
      two arteries of one lower leg had occlusions/stenoses of over 50%. RESULTS: In
      106 patients, there were 132 cases of hemodynamically relevant lesions, and in 26
      patients in two segments. We separately compared 23 cases with aorto-iliac, 82
      with femoro-popliteal and 27 with crural manifestation to the 52 control
      subjects. Calculating age- and sex-adjusted odds ratios, we found that current
      smoking status and plasminogen levels were significantly associated with HRA in
      the aorto-iliac and femoro-popliteal segments, whereas in diabetes mellitus the
      association was found to be in the crural and femoro-popliteal segments. However,
      there was no such association for lipid profiles and fibrinogen. CONCLUSIONS: We
      conclude that the anatomic distribution of HRA in patients with PAD is different
      according to the risk factor profile. The aorto-iliac and crural segments show
      specific risk profiles while the femoro-popliteal segment seems to be a
      transition zone. Smoking and high plasminogen levels may be related to
      atherosclerosis of proximal segments, diabetes to that of the distal segments.

PMID- 11573054
TI  - Arterial status after intravenous TPA therapy for ischaemic stroke. A need for
      further interventions.
AB  - BACKGROUND: Intravenous tissue plasminogen activator (TPA) is an approved therapy
      for acute ischaemic stroke in the United States. We aimed to noninvasively
      monitor the therapy to determine arterial recanalisation and persisting vascular
      abnormalities. METHODS: We prospectively studied consecutive patients with
      symptoms of ischaemic stroke who received intravenous TPA and were monitored by 2
      MHz transcranial Doppler (TCD) to determine occlusion and recanalisation (TIMI
      grades equivalent). For outcome assessment we used the National Institutes of
      Health Stroke Scale (NIHSS) score. RESULTS: Sixty patients were studied (age 71+/
      15 years, pre-TPA NIHSS 18+/-6.1, TPA bolus at 141+/-68 min after stroke onset).
      The internal carotid artery (ICA) was occluded in 25%, middle cerebral artery
      (MCA) in 80%; combined (ICA+MCA) occlusion was found in 19%; and basilar artery
      (BA) was occluded in 7%. Also, 2% had normal TCD and 8% of patients had no
      temporal windows. Complete recanalisation on TCD of all insonated arteries was
      found in 19 patients (32%) at 44+/-22 min after a TPA bolus. However, 67% of MCA,
      25% of BA, and all ICA occlusions did not completely recanalise (TIMI grades 0
      2). If flow impairment persisted for more than two hours after a TPA bolus, these
      patients continued to have significant neurological deficits at 24 hours (15.0+/
      8.2 vs 6.3+/-7.3 NIHSS points, p<0.001 in non-parametric statistics). High-grade
      residual stenoses with microembolic signals were seen on TCD in the MCA and BA
      (n=3) suggesting continuing clot dissolution. In patients without complete
      recanalisation (n=36, or 60%), TCD identified lesions potentially amenable to
      further interventions. CONCLUSIONS: Persisting arterial occlusion after
      intravenous TPA therapy leads to poor short-term outcome. Noninvasive monitoring
      of TPA therapy with TCD can identify these high-risk patients for combined
      interventions such as intra-arterial thrombolysis, mechanical clot disruption,
      stenting or anticoagulation.

PMID- 11573055
TI  - Gelatine-resorcine-formol glue as a sealant of ePTFE patch suture lines.
AB  - BACKGROUND: ePTFE patch reconstruction has superior flow characteristics in
      preventing early thrombus formation during carotid endarterectomy. However
      prolonged bleeding at the suture line of the patch reconstruction is a problem.
      The aim of this study was to investigate whether the application of gelatine
      resorcine-formol (GRF) glue at the suture line can improve local haemostasis.
      METHODS: A prospective randomised trial of 40 consecutive patients undergoing
      carotid endarterectomy was undertaken. Patients were randomised to receive GRF
      glue as a topical haemostatic agent or to act as controls. Statistical analysis
      was performed using the Mann-Whitney test. RESULTS: Although the patch size was
      significantly smaller in the control group (3.0 cm2 vs 4.3 cm2, p<0.001), local
      haemostasis was achieved in half the time when the glue was used (11 min vs 22,
      p<0.004). In the follow-up period ranging from 12 to 24 months, there have been
      no adverse effects related to the glue. Two patients died during the follow-up
      period. These deaths were neither related to the patch nor to the glue.
      CONCLUSIONS: This study has shown that GRF glue is an effective sealant of ePTFE
      patch suture line. GRF glue does not compromise the patch's characteristics.

PMID- 11573056
TI  - Current practice--routine use of shunting in carotid endarterectomy. Cost
      reduction and surgical training.
AB  - BACKGROUND: Sophisticated methods of determining cerebral blood flow have reduced
      the use of shunting in carotid endarterectomy in 6-25% of cases. However teaching
      university hospitals still have to provide their young vascular surgeons with
      experience in the shunting procedure. Since complications of shunting have been
      related to the surgeon's experience in the technique, our study aimed to evaluate
      a policy of the routine use of shunting in carotid endarterectomy by vascular
      surgeons in training. In addition to concluding how this policy would affect the
      optimum outcome of our patients. The probable reduction of hospital charges was
      also evaluated. METHODS: A prospective audit of the results of 423 consecutive
      carotid endarterectomies performed by a senior vascular surgeon (the first 97
      cases) and a vascular surgeon in training under the supervision of a senior
      vascular surgeon (326 cases), with routine use of an indwelling intraluminal
      shunt, in a university hospital in Athens. RESULTS: During the study period, 337
      patients admitted to our department were managed surgically independently of any
      demanding surgery due to the anatomy and the extension of internal carotid artery
      disease. The perioperative stroke/death rate at 30 days was 0.47%, but the stroke
      rate alone was 0%. Minor complications amounted to 5.4%, with an increased but
      not significant difference in patients presenting contralateral internal carotid
      occlusion. There was no difference in complication rates when a young surgeon
      performed the shunting procedure compared with the experienced senior surgeon's
      results, but this was achieved after training in the method in the first 97
      cases. The reduction of the total cost was related to avoidance of cost of the
      devices necessary for determination of the cerebral circulation during carotid
      clamping and the cost of specially trained personnel. Our policy resulted in only
      eight patients having to be treated in the intensive care unit for a total of 13
      days. CONCLUSIONS: Experience in a large number of shunting procedures are
      required for a young vascular surgeon's training, in order to achieve optimum
      results. This can be done in teaching hospitals by using the method more
      frequently than required. Moreover in the contest of continuing changes in the
      practice of carotid endarterectomy and the economic restrictions on health
      expenditure, the routine use of shunting resulted in cost saving without
      jeopardizing the patients' outcome.

PMID- 11573057
TI  - Giacomini's observations on the superficial veins of the abdominal limb and
      principally the external saphenous.
AB  - Carlo Giacomini, later Professor of Anatomy at the University of Turin, Italy,
      presented a thesis on superficial and deep lower limb venous anatomy in July
      1873. This resulted in his name being associated with a vein that he described in
      detail that passes up deep to the fascia on the back of the thigh. However, the
      precise nature of his detailed and insightful observations have not previously
      been presented, at least for the past century. The Authors were able to find and
      translate the original manuscript, and the first section on the superficial veins
      is presented here. Giacomini documented the several variations in the origin and
      terminations, and anterograde and retrograde flow in this vein that have only
      recently been rediscovered by duplex ultrasound scanning. Much can be learned
      from his descriptions by all who are involved in treating chronic venous disease.

PMID- 11573058
TI  - A method for evaluating the thermal threshold in patients with Raynaud's syndrome
      living in temperate areas. A report of three cases.
AB  - BACKGROUND: The concept of "thermal threshold" in Raynaud's syndrome was
      theorized in 1990 by Pratesi as the ambient temperature below which an attack of
      vasospasm is more likely to be provoked, though so far it has not yet been proved
      to be a reality. Our preliminary report of two cases, whose attacks were compared
      with the daily maximum temperatures, showed results suggestive of the existence
      of this parameter. METHODS: We asked a third female patient with Raynaud's
      syndrome of the hands and feet to keep note of the time, days and modalities of
      the phenomena, for at least three months including the summer. Data of six and
      five months from Cases 1 and 2 respectively, not including the times at onset,
      were reconsidered. The data available from all cases were compared to the true
      daily mean temperature. The data of the new Case 3 were also compared with the
      hourly temperatures on each day over the period of study. All calculations
      referred to the estimated temperature to be expected from the difference in
      altitude between the weather stations and the usual and temporary residences.
      RESULTS: The mean thermal threshold was 17.166 degrees C in the less severe Case
      1 and 28.438 degrees C in Case 2 (complicated by gangrene). In Case 3, the mean
      and hourly thresholds were 26.740 and 26.807 degrees C for the hands, and 25.092
      and 23.807 degrees C for the feet, respectively. CONCLUSIONS: This report is
      suggestive, although not conclusively, of the existence of a thermal threshold,
      which is higher in the more severe cases. Further research is required.

PMID- 11573059
TI  - Thromboendarterectomy of the right common iliac artery in a patient with Marfan's
      syndrome and restoration with a new technique.
AB  - Marfan's syndrome is a rare hereditary disease of connective tissue, the surgical
      interest of which is in its propensity to the development of arterial aneurysms.
      We describe the case of a 40-year-old male who was admitted to our hospital
      because of thrombosis of the right common iliac artery and who was treated with a
      new technique: thromboendarterectomy of the right common iliac artery and
      covering of the artery with a synthetic graft, in order to avoid the risk of
      developing an aneurysm of the endarterectomised iliac artery. This is a new
      technique, here described for the first time in the international literature.

PMID- 11573060
TI  - Resolution of a spontaneous coronary artery thrombus with a new antiplatelet
      agent.
AB  - A thrombus was observed in the left anterior descending coronary artery in a 47
      year-old woman who presented with acute anterior myocardial infarction. On a
      coronary angiogram in the right oblique cranial position, the thrombus appeared
      as an eccentric, solid and homogeneous mass with a 22 mm maximal length and 1.9
      mm maximal diameter. The thrombotic segment and the rest of the coronary tree was
      free of atherosclerosis. Due to the inappropriate coronary structure and length
      of the thrombus, coronary angioplasty and/or stent procedures were not performed.
      The patient refused coronary artery by-pass. She was given the glycoprotein
      IIb/IIIa inhibitor tirofiban 0.4 microg x kg(-1) x min(-1) bolus over 30 minutes
      followed by 0.1 microg x kg(-1) x min(-1) for 24 hours, orally acetylsalicylic
      acid 300 mg per day, nytroglicerin 40 mg per day and warfarine with INR being in
      a range of 2-2.5 times. A control coronary angiography performed two months later
      showed total dissolution of the coronary thrombus and clearance of the culprit
      vessel.

PMID- 11573061
TI  - Non-anastomotic midgraft stenosis of a knitted Dacron graft after arterial
      reconstruction. Report of a case.
AB  - Midgraft stenosis of the prosthesis after bypass surgery has seldom been
      reported. A man presented with an ischemic ulcer of the left foot. He had
      undergone bilateral femoropopliteal bypass surgery as well as left-sided
      iliofemoral bypass surgery with a knitted Dacron graft. The graft in his left
      thigh was occluded. A knitted Dacron conduit with 8-mm diameter was interposed
      between the iliofemoral bypass graft and the left profunda femoris artery, and
      graft-popliteal jumping bypass surgery was added. The postoperative angiogram
      showed a short-segmental severe stenosis of the interposed graft neighboring the
      proximal anastomosis. Repeat surgery showed that the stenotic lesion was located
      separately from the anastomosis. This midgraft stenosis was considered to consist
      of dissection of pseudointima associated with the intraoperative procedures. In
      cases of repeat surgery around the inguinal ligament, procedures should be
      performed with great care.

PMID- 11573062
TI  - Oxatomide in the treatment of atopic dermatitis in breast-fed and very young
      infants.
AB  - BACKGROUND: This study was designed to assess the efficacy and safety of
      oxatomide oral suspension, in breast-fed and young babies with atopic dermatitis.
      METHODS: Thirty-one children (11 females, 20 males) aged between 4 and 35 months
      (mean+/- SD 15.4+/-7.6 months) were treated with oxatomide (2.5 mg/mL) at a dose
      of 1 mg/kg/day) split into two doses, every 12 hrs; treatment lasted 30 days.
      Efficacy was evaluated on the basis of the following signs and symptoms: itching
      (severity, extension and duration), blisters (number, extension), erythema
      (severity, extension), papules (number, extension), lesions from scratching
      (yes/no), dry skin (yes/no). RESULTS: Skin signs improved significantly with
      oxatomide. Itching was reduced 58.2% from baseline, and erythema 57.6% (both
      p<0.001). Vesicles, papules, lesions due to scratching and dry skin also improved
      significantly. Oxatomide had to be stopped only in one child in whom the
      dermatitis became worse. CONCLUSIONS: These results show the efficacy and safety
      of oxatomide in breast-fed or very young babies with atopic dermatitis. The oral
      suspension was particularly easy to use in children less than two years old, on
      account of the simple dosage schedule.

PMID- 11573063
TI  - Glucose or sucrose as an analgesic for newborns: a randomised controlled blind
      trial.
AB  - BACKGROUND: To evaluate the effect of different oral glucose or sucrose solutions
      on the pain response to heelstick in newborns. METHODS:  DESIGN: randomised
      double blind placebo controlled trial of water (control) versus one of three
      solutions of glucose - namely 5, 33 and 50% - or one of two solutions of sucrose
      (33% and 50%) or nothing. SETTING: postnatal ward. PATIENTS: seven groups of 20
      healthy newborns (gestational age 38-41, weighing over 2500 g) were randomised to
      receive 2 ml of one of the six solutions on the tongue inmediately before
      heelstick procedure. MAIN OUTCOME MEASURE: heart rate before, during and three
      minutes after the procedure. RESULTS: Even if the trend of the cardiac rates did
      not reach statistic significance, glucose solution 33 and 50% proved to be the
      most effective in reducing pain response. CONCLUSIONS: Sweet solutions may be an
      easy, useful, safe and cheap analgesic for minor invasive procedures in newborns.

PMID- 11573064
TI  - Surgical or conservative treatment of congenital hydronephrosis. Ten years'
      experience.
AB  - BACKGROUND: Controversy exists concerning the ideal management of hydronephrosis
      diagnosed in the perinatal period. Different opinions depend on the absence of an
      accurate tool and of well-defined cut-off values for each test. For these reasons
      we retrospectively evaluated our management protocol. METHODS: Two-hundred and
      seventy-two patients with single system hydronephrosis were evaluated. Patients
      with bilateral hydronephrosis or with other renal or ureteral abnormalities were
      excluded. Diagnosis and grading of hydronephrosis were done by ultrasound. Before
      1995, grade II or greater hydronephrosis was also evaluated with diuretic
      intravenous urography, but in cases studied afterwards, a functional evaluation
      of the obstruction was reached with well tempered diuretic renogram. Indications
      for surgery were considered: recurrent urinary tract infections, grade IV
      hydronephrosis, obstructive drainage pattern and differential renal function less
      than 40%. Patients managed non-operatively received serial re-evaluation with US
      scan, urine test and functional tests if necessary. RESULTS: Hydronephrosis was
      on the right side in 98 cases (36%), and on the left side in the other 174 (64%).
      There were 129 grade I hydronephrosis (47%), 46 grade II (17%), 57 grade III
      (21%), 40 grade IV (15%). Fifty-seven (21%) cases of hydronephrosis underwent
      surgery: 49 (86%) showing obstructive pattern at functional tests, 40 (70%)
      presenting a differential renal function less than 40%, 5 (8%) because recurrent
      urinary tract infections, 40 (70%) affected by grade IV hydronephrosis. No
      children received nephrectomy. Average postoperative follow-up was 2.8 years:
      pelvic dilatation improved or remained unchanged but the obstructive pattern at
      functional tests always disappeared after surgery. The average follow up in the
      observational group of 163 patients (60%) was 4.1 years. In 149 (91%) pelvic
      dilatation improved, but in 14 (9%) it remained unchanged. CONCLUSIONS: The ideal
      management of congenital hydronephrosis is still debated since the natural
      history of these disease is not still completely understood and there is no
      accurate tool to assess these renal units. We believe that grade IV
      hydronephrosis always need surgery as well as those ones with recurrent urinary
      tract infections, longer drainage time or a differential renal function less than
      40%. On the other hand grade I hydronephrosis never need surgery. Mild grade
      hydronephrosis can be safely managed non-operatively with a meticulous follow-up
      and undergoing surgery only when signs of deterioration occur.

PMID- 11573065
TI  - [The evaluation of creative thought: a comparison of methodologies].
AB  - BACKGROUND: To verify the reliability of the evaluation of the original thought
      through verbal tests, processed and standardised with reference to different
      socio-cultural contexts. In this respect we focused our attention on the Torrence
      Test on Creative Thought (TTCT), considering the trans-cultural studies carried
      out by Torrence. METHODS: The analyses were carried out on the linguistic output
      of 116 subjects attending the 4th and 5th years of primary school, responding to
      the first verbal activity of the TTCT. For the evaluation of the Italian output,
      pointing out the Type and Token, morphemes and phrases were considered as basic
      units. The authors calculated the percentage values of occurrence of phrases,
      morphemes and grammatical functions. Then they made cross comparisons between the
      resulting percentage values, found unique morphemes, morphemes recurring only
      twice, as well as phrases characterised by the presence of the aforesaid typology
      of words. RESULTS: TTCT prescriptive evaluation: the percentage (41.19%) is in
      favour of a widespread originality in the phraseological output of our sample.
      Evaluation of phrases/units according to their statistical frequency: 93.39 and
      83.91% respectively of the type/phrases and of the overall phraseological output
      turned out to consist of unique phrases. Originality: Italian linguistic
      production is highly original. Analysis of phrases containing unique and double
      words: the evaluation of Originality according to Torrence's criteria was not
      adequately confirmed in our sample. Functional analysis: it showed that 23.17 and
      41.67% of unique productions acted respectively verbs and as nouns; the only
      analogies in the comparison between American and Italian productions were pointed
      out by analyses carried out according to the criterion of the grammatical
      function of words. CONCLUSIONS: The data from this research bring forward the use
      of tests with verbal contents whose ideational solutions are articulate and
      complex linguistic propositions, validated on people that are different in terms
      of lexical structures and reference context, from those on whom the prescriptive
      criteria are identified and built. With reference to the higher levels of
      Originality noticed in the Italian linguistic output in comparison with American,
      the question is still open if they are linked to creative modes of thought or can
      be referred to specific cultural styles of the Italian language.

PMID- 11573066
TI  - Beta-adrenergic receptor blockers as therapy in pediatric chronic heart failure.
AB  - Beta-adrenergic receptor blocking agents (beta-blockers) are now considered to be
      standard of care for the treatment of chronic congestive heart failure in adults.
      Studies in adults with chronic heart failure have shown that beta-blockers
      improve left ventricular ejection fraction, symptoms, and survival when compared
      to placebo. New mechanisms of actions in individual beta-blockers are being
      continually elucidated, but the primary mechanism of action of beta-blockers in
      chronic heart failure is thought to be the prevention and/or reversal of
      adrenergically-mediated intrinsic myocardial dysfunction and remodeling.
      Experience with the use of beta-blockers in children with heart failure is
      limited but growing. Although no randomized, placebo-controlled data yet exists,
      anecdotal evidence suggests that children with chronic congestive heart failure
      may also benefit from this therapy. There are now uncontrolled safety and
      efficacy studies showing possible benefit from both metoprolol and carvedilol in
      children with heart failure due to either large left-to-right shunt or systemic
      ventricular dysfunction. Large prospective, randomized trials in children are
      currently underway in order to attempt to determine the indications, dosages, and
      optimal use of beta-blockers in children with chronic congestive heart failure.

PMID- 11573067
TI  - Early diagnostic and prognostic indicators in full term infants with neonatal
      cerebral infarction: an integrated clinical, neuroradiological and EEG approach.
AB  - In the last decade the increase in neonatal imaging in infants with abnormal
      neurological signs has highlighted the incidence and the wide spectrum of
      neonatal cerebral infarction. These lesions occur in 1 in 4000 full term infants
      and are often associated with convulsions in the first days after birth. This
      review will cover new knowledge on aetiology and classification of these lesions.
      Special attention will be paid to the value of an integrated approach, using
      clinical, EEG and neuroimaging tools as early diagnostic and prognostic
      indicators of outcome.

PMID- 11573068
TI  - Marijuana use among adolescents: trends, patterns, and influences.
AB  - This article reviews current marijuana conditions, trends, and influences among
      adolescents. Data show that prevalence rates vary markedly among youth, showing
      higher usage rates in the United States and Western Europe and lower rates among
      Mediterranean and Scandinavian youth. Urianalysis studies show that American
      juvenile arrestees are testing positive for cannabis at increasing rates.
      Influences that are central to marijuana use include being older, being male,
      experiencing family conflict, having peer models for use, and suffering from mood
      and anxiety disorders. More information is needed on how much gene-based
      evolutionary traits are relevant to marijuana abuse. Criticisms of school-based
      drug education programs have lead to the emergence of more comprehensive and
      enduring prevention programs. Concern about rising levels of marijuana abuse,
      lack of accountability, and dual diagnoses have given rise to juvenile drug
      courts. Preliminary reports suggest that these two strategies could show promise
      in reducing marijuana use and abuse, although rising THC yields could counteract
      these efforts.

PMID- 11573069
TI  - Influence of thyroid in nervous system growth.
AB  - Nervous system growth and differentiation are closely correlated with the
      presence of iodine and thyroid hormones in initial development stages. In the
      human species, encephalon maturation during the first quarter of pregnancy is
      affected according to recent studies by the transplacenta passage of maternal
      thyroid hormones while it depends on initial iodiothyronin secretion by the
      foetal gland after the 12th week of pregnancy. Thyroid hormone deficiency during
      nervous system development causes altered noble nervous cells, such as the
      pyramidal cortical and Purkinje cells, during glial cell proliferation and
      differentiation alike. Neurons present cell hypoplasia with reduced axon count,
      dendritic branching, synaptic spikes and interneuron connections.
      Oligodendrocytes decrease in number and average myelin content consequently
      drops. Biochemical studies on hypothyroid rats have demonstrated alterations to
      neuron intraplasmatic microtubule content and organisation, changed mitochondria
      number and arrangement and anomalies in T3 nuclear and citoplasmatic receptor
      maturation. Alterations to microtubules are probably responsible for involvement
      of the axon-dendrite system, and are the consequence of deficient thyroid hormone
      action on the mitochondria, the mitochondria enzymes and proteins associated with
      microtubules. Nuclear and citoplasmatic receptors have been identified and gene
      clonation studies have shown two families of nuclear receptors that include
      several sub-groups in their turn. A complex scheme of temporal and spatial
      expression of these receptors exists, so they probably contribute with one
      complementary function, although their physiological role differs. The action of
      thyroid hormones occurs by changing cell protein levels because of their
      regulation at the transcriptional or post-transcriptional level. Genes submitted
      to thyroid hormone control are either expressed by oligodendrytes, which are
      myelin protein coders or glial differentiation mediators, or are nervous cell
      specific, genes coding neurotropins or proteins involved in synaptic excitation.
      The use of new PMRS and MRI non-invasive techniques has enabled identification of
      metabolic and biochemical markers for alterations in the encephalon of untreated
      hypothyroid children. Even an excess of thyroid hormones during early nervous
      system development can cause permanent effects. Hyperthyroidism in fact initially
      induces accelerated maturation process including cell migration and
      differentiation, extension of dendritic processes and synaptogenesis but a later
      excess of thyroid hormones causes reduction of the total number of dendritic
      spikes, due to early interruption of neuron proliferation. Experimental studies
      and clinical research have clarified not only the correlation between nervous
      system maturation and thyroid function during early development stages and the
      certain finding from this research is that both excess and deficient thyroid
      hormones can cause permanent anatomo-functional alterations to the nervous
      system.

PMID- 11573070
TI  - [Biliary atresia syndrome and splenic malformation. A case report].
AB  - Biliary atresia is a severe neonatal malformation in which the entire
      extrahepatic biliary tract or part of it is absent and replaced by fibrosclerotic
      tissue. Having been described for the first time by Thomson in 1891, biliary
      atresia has an incidence of 1:10,000-15,000 live neonates with a slight
      predominance in the female sex; it is associated with other malformations in 25%
      of cases. In 1993 Davenport et al. identified a subgroup of patients with biliary
      atresia who presented a splenic malformation. This condition was known as biliary
      atresia and splenic malformation syndrome (BASM). The cases of biliary atresia
      and BASM are still not clear and a number of etiopathogenetic hypotheses have
      been put forward. The treatment is surgical and includes a first stage of hepatic
      porto-enteroanastomosis using a defunctionalised Roux loop (Kasal), followed by
      the definitive operation comprising liver transplant. We report the case of a boy
      who was brought to our attention with jaundice, polypnea and hepatosplenomegalia;
      instrumental tests allowed the diagnosis of biliary atresia, median liver,
      stomach and spleen on the right, polysplenia, atresia of the intrahepatic tract
      of the inferior vena cava, presence of a superior vena cava to the left that
      drained into the upper left portion of the common atrium. Moreover, the cardiac
      apex was present on the right, extensive DIA of the common atrium type, extensive
      DIV and right aortic arch.

PMID- 11573071
TI  - [Neonatal thrombosis of the middle cerebral artery. Three clinical cases with a
      24-month follow up].
AB  - Three patients with neonatal thrombosis of the middle cerebral artery are
      described. In two patients the thrombosis was secondary to neonatal asphyxia. The
      third patient had a porencephalic cyst twenty days after birth suggesting a
      prenatal origin of the thrombotic event. The follow-up was carried out for two
      years. In the first year, two patients had infantile spasms and hyparrhythmic
      pattern of EEG. This type of epilepsy has never been previously reported.
      Futhermore, all three patients presented hemiplegia and reduction of cranial
      circumference. The neuroradiologic procedures showed to be very useful for the
      diagnosis and long term follow-up. These patients must be followed carefully
      since the development of a subsequent epilepsy is reported to be approx 11%.

PMID- 11573072
TI  - True tail dorsal-lumbar: malformation or ancestral remaining?
AB  - The case of a healthy newborn presenting a dorsal-lumbar cutaneous appendage is
      reported. The appendage was excised by ligature. This appendage was not
      associated with dysraphism or other malformations. It was analysed histologically
      and then defined as a so called true tail. Although it was been expressed a lot
      of hypotheses, the etiology of this finding remains disputed. The embryology of
      malformation and its non identification between known-syndromes is showed. The
      difference between true tails and not-true tails is discussed. The conclusion is
      drawn that for its clinical and histological aspect this malformation may be
      included in true tails.

PMID- 11573073
TI  - [BMS: S for syndrome or S for symptom? A reappraisal of the burning mouth
      syndrome].
AB  - In this article, some nosological and ethiopathogenetic aspects of Burning Mouth
      Syndrome (BMS) are critically evaluated. Despite the number of papers frequently
      published on this subject, there is still no universally accepted definition of
      this disorder. Therefore, a premise on which to base an experimental approach is
      missing. This also leads to a lack of parameters for comparing the clinical
      experimental experiences reported in various studies in this field. Moreover, it
      makes it rather easy to verify the absence of definitive scientific proof as
      well. Such proof would allow researches to consider the etiological aspects
      presented in the literature thus far as certain. Due to this lack of certainty,
      it might be prudent to introduce the concept of idiopathic (or essential) BMS to
      indicate a burning sensation in the oral cavity when the etiology is unknown and
      not correlated to noticeable local or systemic alterations. This would be true
      BMS. In other words, many local and/or systemic anomalies could lead to a burning
      type of symptomatology localised in the oral cavity but this does not constitute
      a sufficient requisite to indicate a diagnosis of BMS, according to the authors.

PMID- 11573074
TI  - [Activation of mandibular growth with the Fraenkel II device: assessment of
      effects on the vertical plane].
AB  - BACKGROUND: The aim of the study was to evaluate if a function Fraenkel II
      Regulator therapy can increase the vertical dimension of the cranio-facial
      district. Enlow's cephalometric analysis was used to measure the proportion
      between cranial and facial components without references to the population
      average. METHODS: Twenty patients were selected, with dental class II, skeletal
      class II and mandibular hypoplasy and normal facial biotype. The patients were
      treated for 24 months only with Fraenkel II and the appliances was activated 2 mm
      every 6 months. The follow-up was of the 2 years and cephalometric tracings were
      made at the beginning and after therapy. RESULTS: The results showed an increase
      of vertical dimension and the change of occlusal plane inclination after the
      therapy. This inclination compensates basal dysarmonies and increases the
      vertical dimension. CONCLUSIONS: The results are not statistically significant,
      but they underline the importance of Fraenkel's regulator function to change
      negative tendency growth.

PMID- 11573075
TI  - [Burrs breaking in oral surgery: a experimental study].
AB  - BACKGROUND: This experimental work came out from clinic observations. The deal is
      to check the factors that can provoke the fracture of the more commonly in oral
      surgery used burrs, and then reduce the correlated risks to this event. Besides a
      fracture surface characterisation is done to point out the presence of production
      and/or stoking defects that can alter the structure. METHODS: Four batches of new
      surgical burrs (type Lindemann) were examined for a total of 40 samples. The
      first batch was used as control, the other three were submitted to 5, 10 and 20
      sterilisation cycles respectively. Before each cycle disinfectant washing was
      done. All the samples were then mechanical tested (four point bending test) for
      the determination of the ultimate tension strength. The fracture surfaces were
      observed at SEM; a comparison with that of burrs broken during surgery operations
      was done. RESULTS: The new burrs did not show working defects. The washing and
      sterilisation processes did not provoke any corrosion attack. CONCLUSIONS: No
      significant differences among the batches were detected from the mechanical tests
      as well as from micrographic observations.

PMID- 11573076
TI  - [Baropodometric examination for complete diagnosis of patients with cranio
      cervico-mandibular disorders].
AB  - BACKGROUND: The aim of this study was to evaluate the relationship between
      craniomandibular disorders and postural alterations using baropodometric
      examination. METHODS: All tests were carried out in the Department of Dentistry
      at Sassari University in a population of patients with cranio-cervico-mandibular
      disorders (CCMD) of various types and severity. A total of 10 subjects (mean age
      approximately 30 years) with this pathology were evaluated over 7 months. All
      patients were treated using the following protocol: objective functional and
      clinical examination, radiographic tests, occlusal treatment using acrylic resin
      plate, baropodometric test with static and dynamic posture assessment, with eyes
      open and closed, before and after treatment with orthesis. RESULTS: An improved
      postural position was observed in 80% of cases, of which 30% showed an
      improvement in both static and dynamic posture, 20% only in static and 30% only
      in dynamic; these results highlighted the importance of baropodometric analysis
      in the correct treatment of patients with CCMD and postural disorders.
      CONCLUSIONS: This study confirms the need for a holistic approach to
      odontostomatological disciplines and the importance of a modern preventive and/or
      therapeutic approach to orthodontic problems and CCMD, especially when fixed or
      removable biomechanical devices are used.

PMID- 11573077
TI  - [Unusual case of hypercondensing malignant osteodysplasty: osteopetrosis].
AB  - Osteopetrosis, known also as Albers-Schonberg disease, is a genetic disorder
      causing a generalized sclerosis of the bones and the reduction of the marrow. The
      diagnosis is often secondary to pathologic processes and its usually observed
      through specific X-ray researches. The principal cause of osteopetrosis is to
      attribute to a deficit of bone resorption and remodelling. Osteomyelitis is a
      complication of osteopetrosis. The purpose of this article is based on several
      point: 1) to know the cause of osteopetrosis, then to classify and check it; 2)
      to present the case who did not respond to of a patient with osteopetrosis
      complicated by maxillary and phalanx osteomyelitis common therapies and give an
      accurate analysis.

PMID- 11573079
TI  - With the ends in sight: images from the BRCA1 tumor suppressor.

PMID- 11573080
TI  - A cell death-promoting kinase.

PMID- 11573081
TI  - The anatomy of infidelity.

PMID- 11573082
TI  - A sliding clamp monkey wrench.

PMID- 11573083
TI  - The X-ray files.

PMID- 11573084
TI  - Picture story. A hormone receptor springs into action.

PMID- 11573085
TI  - Structure of a BRCA1-BARD1 heterodimeric RING-RING complex.
AB  - The RING domain of the breast and ovarian cancer tumor suppressor BRCA1 interacts
      with multiple cognate proteins, including the RING protein BARD1. Proper function
      of the BRCA1 RING domain is critical, as evidenced by the many cancer
      predisposing mutations found within this domain. We present the solution
      structure of the heterodimer formed between the RING domains of BRCA1 and BARD1.
      Comparison with the RING homodimer of the V(D)J recombination-activating protein
      RAG1 reveals the structural diversity of complexes formed by interactions between
      different RING domains. The BRCA1-BARD1 structure provides a model for its
      ubiquitin ligase activity, illustrates how the BRCA1 RING domain can be involved
      in associations with multiple protein partners and provides a framework for
      understanding cancer-causing mutations at the molecular level.

PMID- 11573086
TI  - Crystal structure of the BRCT repeat region from the breast cancer-associated
      protein BRCA1.
AB  - The C-terminal BRCT region of BRCA1 is essential for its DNA repair,
      transcriptional regulation and tumor suppressor functions. Here we determine the
      crystal structure of the BRCT domain of human BRCA1 at 2.5 A resolution. The
      domain contains two BRCT repeats that adopt similar structures and are packed
      together in a head-to-tail arrangement. Cancer-causing missense mutations occur
      at the interface between the two repeats and destabilize the structure. The
      manner by which the two BRCT repeats interact in BRCA1 may represent a general
      mode of interaction between homologous domains within proteins that interact to
      regulate the cellular response to DNA damage. The structure provides a basis to
      predict the structural consequences of uncharacterized BRCA1 mutations.

PMID- 11573087
TI  - Arsenate reductase from S. aureus plasmid pI258 is a phosphatase drafted for
      redox duty.
AB  - Arsenate reductase (ArsC) from Staphylococcus aureus plasmid pI258 plays a role
      in bacterial heavy metal resistance and catalyzes the reduction of arsenate to
      arsenite. The structures of the oxidized and reduced forms of ArsC were solved.
      ArsC has the PTPase I fold typical for low molecular weight tyrosine phosphatases
      (LMW PTPases). Remarkably, kinetic experiments show that pI258 ArsC also
      catalyzes the tyrosine phosphatase reaction in addition to arsenate reduction.
      These results provide evidence that ArsC from pI258 evolved from LMW PTPase by
      the grafting of a redox function onto a pre-existing catalytic site and that its
      evolutionary origin is different from those of arsenate reductases from
      Escherichia coli plasmid R773 and from Saccharomyces cerevisiae. The mechanism
      proposed here for the catalysis of arsenate reduction by pI258 ArsC involves a
      nucleophilic attack by Cys 10 on arsenate, the formation of a covalent
      intermediate and the transport of oxidative equivalents by a disulfide cascade.
      The reaction is associated with major structural changes in the ArsC.

PMID- 11573088
TI  - Crystal structure and kinetic analysis of beta-lactamase inhibitor protein-II in
      complex with TEM-1 beta-lactamase.
AB  - The structure of the 28 kDa beta-lactamase inhibitor protein-II (BLIP-II) in
      complex with the TEM-1 beta-lactamase has been determined to 2.3 A resolution.
      BLIP-II is a secreted protein produced by the soil bacterium Streptomyces
      exfoliatus SMF19 and is able to bind and inhibit TEM-1 with subnanomolar
      affinity. BLIP-II is a seven-bladed beta-propeller with a unique blade motif
      consisting of only three antiparallel beta-strands. The overall fold is highly
      similar to the core structure of the human regulator of chromosome condensation
      (RCC1). Although BLIP-II does not share the same fold with BLIP, the first beta
      lactamase inhibitor protein for which structural data was available, a comparison
      of the two complexes reveals a number of similarities and provides further
      insights into key components of the TEM-1-BLIP and TEM-1-BLIP-II interfaces. Our
      preliminary results from gene knock-out studies and scanning electron microscopy
      also reveal a critical role of BLIP-II in sporulation.

PMID- 11573089
TI  - Ca2+-independent binding of an EF-hand domain to a novel motif in the alpha
      actinin-titin complex.
AB  - The interaction between alpha-actinin and titin, two modular muscle proteins, is
      essential for sarcomere assembly. We have solved the solution structure of a
      complex between the calcium-insensitive C-terminal EF-hand domain of alpha
      actinin-2 and the seventh Z-repeat of titin. The structure of the complex is in a
      semi-open conformation and closely resembles that of myosin light chains in their
      complexes with heavy chain IQ motifs. However, no IQ motif is present in the Z
      repeat, suggesting that the semi-open conformation is a general structural
      solution for calcium-independent recognition of EF-hand domains.

PMID- 11573090
TI  - UDP-galactopyranose mutase has a novel structure and mechanism.
AB  - Uridine diphosphogalactofuranose (UDP-Galf ) is the precursor of the d
      galactofuranose (Galf ) residues found in bacterial and parasitic cell walls,
      including those of many pathogens, such as Mycobacterium tuberculosis and
      Trypanosoma cruzi. UDP-Galf is made from UDP-galactopyranose (UDP-Galp) by the
      enzyme UDP-galactopyranose mutase (mutase). The mutase enzyme is essential for
      the viability of mycobacteria and is not found in humans, making it a viable
      therapeutic target. The mechanism by which mutase achieves the unprecedented ring
      contraction of a nonreducing sugar is unclear. We have solved the crystal
      structure of Escherichia coli mutase to 2.4 A resolution. The novel structure
      shows that the flavin nucleotide is located in a cleft lined with conserved
      residues. Site-directed mutagenesis studies indicate that this cleft contains the
      active site, with the sugar ring of the substrate UDP-galactose adjacent to the
      exposed isoalloxazine ring of FAD. Assay results establish that the enzyme is
      active only when flavin is reduced. We conclude that mutase most likely functions
      by transient reduction of substrate.

PMID- 11573091
TI  - A covalent crosslink converts the hammerhead ribozyme from a ribonuclease to an
      RNA ligase.
AB  - The hammerhead ribozyme is a more efficient ribonuclease than an RNA ligase.
      Under typical reaction conditions, the rate of RNA chain cleavage is
      approximately 100-fold faster than the rate of the reverse ligation reaction such
      that virtually all of the hammerhead is in its cleaved form at equilibrium. Here
      we show that the introduction of a crosslink away from the catalytic core of the
      hammerhead has little effect on the cleavage rate but dramatically increases the
      ligation rate, thereby making the hammerhead an efficient RNA ligase. This
      experiment emphasizes the role of molecular flexibility in defining the
      properties of a macromolecular catalyst and suggests why other small ribozymes
      are more efficient ligases than ribonucleases.

PMID- 11573092
TI  - Electron cryomicroscopy and bioinformatics suggest protein fold models for rice
      dwarf virus.
AB  - The three-dimensional structure of rice dwarf virus was determined to 6.8 A
      resolution by single particle electron cryomicroscopy. By integrating the
      structural analysis with bioinformatics, the folds of the proteins in the double
      shelled capsid were derived. In the outer shell protein, the uniquely orientated
      upper and lower domains are composed of similar secondary structure elements but
      have different relative orientations from that of bluetongue virus in the same
      Reoviridae family. Differences in both sequence and structure between these
      proteins may be important in defining virus-host interactions. The inner shell
      protein adopts a conformation similar to other members of Reoviridae, suggesting
      a common ancestor that has evolved to infect hosts ranging from plants to
      animals. Symmetry mismatch between the two shells results in nonequivalent, yet
      specific, interactions that contribute to the stability of this large
      macromolecular machine.

PMID- 11573093
TI  - Interaction of coxsackievirus B3 with the full length coxsackievirus-adenovirus
      receptor.
AB  - Group B coxsackieviruses (CVB) utilize the coxsackievirus-adenovirus receptor
      (CAR) to recognize host cells. CAR is a membrane protein with two Ig-like
      extracellular domains (D1 and D2), a transmembrane domain and a cytoplasmic
      domain. The three-dimensional structure of coxsackievirus B3 (CVB3) in complex
      with full length human CAR and also with the D1D2 fragment of CAR were determined
      to approximately 22 A resolution using cryo-electron microscopy (cryo-EM). Pairs
      of transmembrane domains of CAR associate with each other in a detergent cloud
      that mimics a cellular plasma membrane. This is the first view of a virus
      receptor interaction at this resolution that includes the transmembrane and
      cytoplasmic portion of the receptor. CAR binds with the distal end of domain D1
      in the canyon of CVB3, similar to how other receptor molecules bind to entero-
      and rhinoviruses. The previously described interface of CAR with the adenovirus
      knob protein utilizes a side surface of D1.

PMID- 11573094
TI  - Quantitative protein stability measurement in vivo.
AB  - The equilibrium between the native and denatured states of a protein can be key
      to its function and regulation. Traditionally, the folding equilibrium constant
      has been measured in vitro using purified protein and simple buffers. However,
      the biological environment of proteins can differ from these in vitro conditions
      in ways that could significantly perturb stability. Here, we present the first
      quantitative comparison between the stability of a protein in vitro and in the
      cytoplasm of Escherichia coli using amide hydrogen exchange detected by MALDI
      mass spectrometry (SUPREX). The results indicate that the thermodynamic stability
      of monomeric lambda repressor within the cell is the same as its stability
      measured in a simple buffer in vitro. However, when the E. coli are placed in a
      hyperosmotic environment, the in vivo stability is greatly enhanced. The in vivo
      SUPREX method provides a general and quantitative way to measure protein
      stabilities in the cell and will be useful for applications where intracellular
      stability information provides important biological insights.

PMID- 11573095
TI  - Structure of the KcsA channel intracellular gate in the open state.
AB  - Ion channels catalyze the selective transfer of ions across the membrane in
      response to a variety of stimuli. These channels gate by controlling the access
      of ions to a centrally located water-filled pore. The crystal structure of the
      Streptomyces lividans potassium channel (KcsA) has allowed a molecular
      exploration of this mechanism. Electron paramagnetic resonance (EPR) studies have
      uncovered significant conformational changes at the intracellular end of the
      second transmembrane helix (TM2) upon gating. We have used site-directed spin
      labeling (SDSL) and EPR spectroscopy in an attempt to quantify the structural
      rearrangements of the KcsA TM2 bundle underlying the transition from the closed
      to the open state. Under conditions favoring the closed and open conformations,
      10 intersubunit distances were obtained across TM2 segments from tandem dimer
      constructs. Analysis of these data points to a mechanism in which each TM2 helix
      tilts away from the permeation pathway, towards the membrane plane, and rotates
      about its helical axis, supporting a scissoring-type motion with a pivot point
      near residues 107-108. These movements are accompanied by a large increase in the
      diameter of the vestibule below the central water-filled cavity.

PMID- 11573096
TI  - Observation of signal transduction in three-dimensional domain swapping.
AB  - p13suc1 (suc1) has two native states, a monomer and a domain-swapped dimer. The
      structure of each subunit in the dimer is identical to that of the monomer,
      except for the hinge loop that connects the exchanging domains. Here we find that
      single point mutations at sites throughout the protein and ligand binding both
      shift the position of the equilibrium between monomer and dimer. The hinge loop
      was shown previously to act as a loaded molecular spring that releases tension
      present in the monomer by adopting an alternative conformation in the dimer. The
      results here indicate that the release of strain propagates throughout the entire
      protein and alters the energetics of regions remote from the hinge. Our data
      illustrate how the signal conferred by the conformational change of a protein
      loop, elicited by domain swapping, ligand binding or mutation, can be sensed by a
      distant active site. This work highlights the potential role of strained loops in
      proteins: the energy they store can be used for both signal transduction and
      allostery, and they could steer the evolution of protein function. Finally, a
      structural mechanism for the role of suc1 as an adapter molecule is proposed.

PMID- 11573097
TI  - Metal ion coordination by the AGC triad in domain 5 contributes to group II
      intron catalysis.
AB  - Group II introns require numerous divalent metal ions for folding and catalysis.
      However, because little information about individual metal ions exists,
      elucidating their ligands, functional roles and relationships to each other
      remains challenging. Here we provide evidence that an essential motif at the
      catalytic center of the group II intron, the AGC triad within domain 5 (D5),
      provides a ligand for a crucial metal ion. Sulfur substitution of the pro-Sp
      oxygen of the adenosine strongly disrupts D5 binding to a substrate consisting of
      an exon and domains 1-3 of the intron (exD123). Cd2+ rescues this effect by
      enabling the sulfur-modified D5 to bind to exD123 with wild type affinity and
      catalyze 5'-splice site cleavage. This switch in metal specificity implies that a
      metal ion interacts with D5 to mediate packing interactions with D123. This new
      D5 metal ion rescues the disruption of D5 binding and catalysis with a
      thermodynamic signature different from that of the metal ion that stabilizes the
      leaving group during the first step of splicing, suggesting the existence of two
      distinct metal ions.

PMID- 11573098
TI  - Crystal structures of the catalytic domain of human protein kinase associated
      with apoptosis and tumor suppression.
AB  - We have determined X-ray crystal structures with up to 1.5 A resolution of the
      catalytic domain of death-associated protein kinase (DAPK), the first described
      member of a novel family of pro-apoptotic and tumor-suppressive serine/threonine
      kinases. The geometry of the active site was studied in the apo form, in a
      complex with nonhydrolyzable AMPPnP and in a ternary complex consisting of
      kinase, AMPPnP and either Mg2+ or Mn2+. The structures revealed a previously
      undescribed water-mediated stabilization of the interaction between the lysine
      that is conserved in protein kinases and the beta- and gamma-phosphates of ATP,
      as well as conformational changes at the active site upon ion binding. Comparison
      between these structures and nucleotide triphosphate complexes of several other
      kinases disclosed a number of unique features of the DAPK catalytic domain, among
      which is a highly ordered basic loop in the N-terminal domain that may
      participate in enzyme regulation.

PMID- 11573100
TI  - Bismuth-based quadruple therapy with bismuth subcitrate, metronidazole,
      tetracycline and omeprazole in the eradication of Helicobacter pylori.
AB  - BACKGROUND: A previous study showed that 14 days of qid bismuth-based triple
      therapy with tetracycline 500 mg, metronidazole 250 mg and colloidal bismuth
      subcitrate 120 mg resulted in excellent Helicobacter pylori eradication rates
      (89.5%). The present study looked at a shorter treatment period by adding
      omeprazole and by reducing the dose of tetracycline. METHODS: One hundred sixty
      one patients with H pylori confirmed by histology and (13)carbon urea breath test
      were included in the study. They were treated for seven days with bismuth
      subcitrate 120 mg plus metronidazole 250 mg plus tetracycline 250 mg qid plus
      omeprazole 20 mg bid (OBMT). Patients were 18 to 75 years of age and had
      dyspepsia with or without a history of peptic ulcer. Patients with irritable
      bowel syndrome, active ulcer or previous attempt at eradication, or those who had
      used antibiotics or antiulcer drugs in the previous 30 days were excluded.
      Eradication was determined by two (13)carbon urea breath tests done one and three
      months, respectively, after treatment. Strains with minimal inhibitory
      concentrations of 8 microg/mL or higher were considered to be resistant to
      metronidazole. RESULTS: The overall per protocol eradication rate was 84%-89.5%
      in metronidazole-sensitive and 70.8% in metronidazole-resistant strains. Modified
      intent-to-treat analysis resulted in a 80% eradication rate--82.5% in
      metronidazole-sensitive and 66.7% in metronidazole-resistant strains. Only one
      patient discontinued treatment because of adverse events. CONCLUSIONS: The OBMT
      regimen used in this study is safe and effective against metronidazole-sensitive
      H pylori strains.

PMID- 11573101
TI  - Colonic disorders in adult cystic fibrosis.
AB  - By 1996, the median survival of patients with cystic fibrosis (CF) in North
      America had increased to 31 years. With the markedly improved life expectancy,
      many CF patients are now adults. There is an associated increased risk of certain
      colonic disorders, and the emergence of other previously unrecognized disorders,
      in adult CF patients. The distal intestinal obstruction syndrome (DIOS), which is
      more common in older patients, is a frequent cause of abdominal pain.
      Intussusception may complicate DIOS; other differential diagnoses include
      appendiceal disease, volvolus, Crohn's disease, fibrosing colonopathy and colonic
      carcinoma. The diagnosis of acute appendicitis, although uncommon in patients
      with CF, is often delayed, and appendiceal abscess is a frequent complication.
      The prevalence of Crohn's disease in CF has been shown to be 17 times that of the
      general population. Right-sided microscopic colitis is a recently recognized
      entity in CF of uncertain clinical significance. Fibrosing colonopathy has been
      confined mostly to children with CF, attributed to the use of high strength
      pancreatic enzyme supplements, but it has been reported in three adults. Nine
      cases of carcinoma of the large intestine have been reported worldwide,
      associated with an apparent excess risk of digestive tract cancers in CF. Despite
      high carrier rates of Clostridium difficile in patients with CF, pseudomembranous
      colitis is distinctly rare, but severe cases complicated by toxic megacolon have
      been reported. In these patients, watery diarrhea is often absent. Adult CF
      patients with refractory or unexplained intestinal symptoms merit thorough
      investigations.

PMID- 11573102
TI  - The updated Sydney system: classification and grading of gastritis as the basis
      of diagnosis and treatment.
AB  - In recent years, the importance of the histological diagnosis of gastritis on the
      basis of routinely obtained antral and corpus biopsies has increased enormously,
      which is owed not least of all to the discovery of Helicobacter pylori. The
      introduction of the Sydney system made it possible, for the first time, to grade
      histological parameters, identify topographical distribution and, finally, make a
      statement about the etiopathogenesis of the gastritis. Of pathogenetic importance
      is, in the first instance, the differentiation between gastritis with and
      gastritis without H pylori infection. The group of H pylori-associated gastritis
      can be further subdivided into forms of gastritis whose morphological
      distribution patterns usually identify them as sequelae of H pylori infection,
      while the group of gastritis unassociated with H pylori, can be differentiated
      into autoimmune, chemically induced reactive gastritis, ex-H pylori gastritis,
      Helicobacter heilmannii gastritis, Crohn's gastritis and a number of special
      forms of gastritis.

PMID- 11573103
TI  - Reactivation of hepatitis B e antigen-negative chronic hepatitis B in a bone
      marrow transplant recipient following lamivudine withdrawal.
AB  - Reactivation of hepatitis B virus (HBV) is a recognized complication of bone
      marrow transplantation (BMT). Lamivudine is a nucleoside analogue with potent
      antiviral activity that has been used in the prophylaxis of HBV reactivation in
      at-risk BMT recipients. Currently, no data exist regarding the safety of
      nucleoside analogue withdrawal in these patients. A 32-year-old BMT recipient
      with hepatitis B e antigen (HBeAg)-negative, chronic HBV who developed a serious
      flare of hepatic inflammation due to a rebound in viral replication within 12
      weeks of discontinuing lamivudine therapy is described. The patient remained
      HBeAg-negative despite high level viremia, suggesting the emergence of a mutant
      viral strain. The patient's acute hepatitis resolved promptly with the
      reinstitution of lamivudine therapy. Further studies are necessary to define the
      safety and efficacy of nucleoside analogues in the prevention of HBV reactivation
      in at-risk BMT recipients. Clinicians should consider the risk of inducing
      serious flares of hepatic inflammation due to abrupt nucleoside analogue
      withdrawal in these patients.

PMID- 11573104
TI  - Giant cell myocarditis, in a patient with Crohn's disease, treated with
      etanercept--a tumour necrosis factor-alpha antagonist.
AB  - Cardiac disease in association with inflammatory bowel disease (IBD) is uncommon.
      Reports include pericarditis, pericardial effusion, myocarditis, myocardial
      infarction, endocarditis and arrythmias. Myocardial inflammation related to IBD
      may be due to a drug hypersensitivity reaction or micronutrient deficiency, or
      may be secondary to the underlying IBD as an extraintestinal manifestation. In
      this setting, myocarditis usually presents as congestive heart failure and/or
      refractory arrhythmia. Prognosis varies among reported cases, including complete
      recovery, remission with recurrence and fatal disease. Treatment of myocarditis
      has included aminosalicylates and immunosuppressive medications. Recently, newer
      therapies for IBD have been developed, such as tumour necrosis factor-alpha (TNF
      a) antagonists. The present report describes a case of a 46-year-old man with
      clinical and endoscopic evidence of moderately active colonic Crohn's disease who
      developed congestive heart failure due to giant cell myocarditis. Little clinical
      improvement occurred with immunosuppressive therapy. Only after the addition of
      etanercept, a TNF-a p75 receptor antagonist, did complete clinical resolution
      occur. These authors conclude that the use of TNF-a antagonists may be considered
      in the treatment of life-threatening extraintestinal manifestations of
      inflammatory bowel disease.

PMID- 11573106
TI  - NSAID-induced small bowel diaphragms and strictures diagnosed with intraoperative
      enteroscopy.
AB  - Nonsteroidal anti-inflammatory drugs are known to cause mucosal damage in the
      stomach and duodenum, which may lead to hemorrhage and perforation. However,
      these medications may also cause damage in the more distal small bowel. Due to
      the location of these lesions, currently available diagnostic testing may yield
      false negative results. Two cases of nonsteroidal anti-inflammatory drug-induced
      small bowel diaphragms presenting as obscure gastrointestinal hemorrhage and
      recurrent small bowel obstruction, respectively, are discussed. Intraoperative
      enteroscopy was used to confirm this diagnosis after other diagnostic tests
      failed to identify the etiology. This procedure may increase the accuracy of
      exploratory laparotomy in these challenging cases.

PMID- 11573105
TI  - An unusual case of hepatic abscess.
AB  - A case of recurring primary hepatic actinomycosis is reported. A 50-year-old man
      presented with fever, weight loss and multiple hepatic masses. A diagnosis was
      obtained by cytological examination of a biopsy sample taken from the largest
      hepatic mass, which revealed the presence of Actinomyces species. The patient was
      treated with penicillin for 12 months and did well. Seven years later, he
      presented with similar symptoms but with a single large liver mass and a
      pulmonary infiltrate in the right lower lobe. Liver biopsy showed an inflammatory
      pseudotumour, and lung biopsy showed the presence of Actinomyces species. Again,
      the patient was treated with penicillin. Five months later, the patient was doing
      well, and a follow-up computed tomography scan showed partial regression of the
      hepatic pseudotumour. This case indicates that hepatic actinomycosis can recur
      several years after an appropriate treatment and stresses the need for careful
      follow-up in such patients.

PMID- 11573107
TI  - Diagnosis and classification of inflammatory bowel disease.

PMID- 11573108
TI  - Liver enzymes as surrogate markers of hepatitis C histopathology--avoiding the
      liver biopsy needle?

PMID- 11573109
TI  - Uses of internet technology in clinical practice.
AB  - The practice of medicine has extended itself to vast areas and requires active
      clinicians to systematize and organize their workload through the use of the most
      up-to-date digital and computer communication technologies. Computerization and
      worldwide accessibility of information has especially provided great assistance
      in this regard. The explosive growth of medical information increases the need
      for the use of these new methods of organizing and accessing data. This article
      briefly summarizes a few of the vital tools that internet technology has provided
      clinical practice, with the aid of basic concepts of internet, database systems,
      hospital systems and data security and reliability.

PMID- 11573110
TI  - Attention deficit hyperactivity disorder. Epidemiologic, pathophysiologic,
      diagnostic and treatment perspectives.
AB  - Although attention deficit hyperactivity disorder is a common child psychiatric
      disorder, the epidemiology and pathophysiology of attention deficit hyperactivity
      disorder is variable in different studies. Attention deficit hyperactivity
      disorder and comorbid disorders in children aided both by attention deficit
      hyperactivity disorder diagnostic criteria and assessment scales entails a
      comprehensive neuropsychiatric interview plus collection of information from
      different sources. Although psychosocial and behavioral therapies are of great
      therapeutic values, the psychopharmacological drugs are often used in the
      treatment of patients with attention deficit hyperactivity disorder. With a
      combined approach, a substantial proportion of patients with attention deficit
      hyperactivity disorder (90%) show good recovery. The patients with attention
      deficit hyperactivity disorder need careful evaluation and appropriate long-term
      treatment in order to prevent subsequent negative consequences. In rapidly
      developing countries, the researchers should carry out studies, which explore
      different aspects of attention deficit hyperactivity disorder in children,
      adolescents and adults.

PMID- 11573111
TI  - Neuroblastoma.
AB  - OBJECTIVE: Due to the poor results achieved on combination chemotherapy and the
      unproven cost-effectiveness value of myeloablative therapy, the question has been
      raised; should patients with stage IV neuroblastoma be actively treated? The aim
      of the current study is to analyze retrospectively treatment results of 43
      children with neuroblastoma with special stress on the rate and duration of
      remission in children with disseminated neuroblastoma. METHODS: Treatment of
      children with neuroblastoma consisted of surgical removal of the tumor, if
      possible, followed by chemotherapy for unresectable residual tumor including
      metastases. Second look surgery was performed to resect residual masses rendered
      resectable on chemotherapy in the absence of distal metastases. The chemotherapy
      protocol used in the current study consisted of alternating combination
      chemotherapy regimens containing, Cyclophosphamide, Vincristine and Doxorubicin,
      alternating with Cis-platinum and Etoposide. RESULTS: The male to female ratio
      was 2:1 with a median age of 2.1 years. The abdomen was the primary site of
      involvement encountered in 32 patients (74%). According to the childrens cancer
      study group (CCSG) staging system, only 6 patients (14%) had localized tumors
      (stages I and II). Two patients (5%) were found to have stage IV. Stage III was
      documented in 5 patients (12%). The majority of patients (70%) had disseminated
      disease at presentation. The bone marrow was the most common site of metastatic
      deposit, encountered in 23 patients out of the 30 with stage IV disease (77%).
      Out of the 12 evaluable non-stage IV patients, only one patient (8%) showed
      treatment failure. Assessment of response by the end of the 6th month from the
      date of diagnosis revealed that out of the 27 evaluable patients with stage IV, 4
      patients achieved complete remission, 7 patients achieved very good partial
      remission, 8 patients achieved partial remission and 4 patients achieved mixed
      response. Three patients showed progressive disease on chemotherapy. Twenty-one
      patients (78%) were symptom-free and were conducting normal life. Assessment of
      response to treatment by the end of the 12th month from diagnosis revealed that 6
      patients (2 complete remissions, 1 very good partial response, 3 partial
      responses) were maintaining their remission. Out of the 19 patients showing
      complete or partial remission at early assessment, 4 patients maintained their
      remission for more than 18 months. Two (one was in complete remission and the
      other was in partial response) of them progressed in areas of previous
      involvement after 20 and 21 months. The other 2 patients (one was in complete
      remission and the other was in partial response) showed disease progression in
      areas not previously affected by disease at presentation after 23 and 42 months.
      CONCLUSION: Results of treatment by multiagent chemotherapy regimens used in the
      current study show that children with neuroblastoma, even those with advanced
      stages, should receive the benefit of intensive multimodal therapy, even those
      with partial response to initial therapy. These patients may experience
      reasonable symptom-free and sometimes, disease-free survival.

PMID- 11573112
TI  - Laparoscopic cholecystectomy in patients with Sickle Cell Disease.
AB  - OBJECTIVE: To determine the safety and benefits of laparoscopic cholecystectomy
      as the standard surgical treatment for gallstones in patients with sickle cell
      anemia. METHODS: Thirty-six sicklers and 111 non-sickler patients from the
      eastern province of the Kingdom of Saudi Arabia who were admitted to Qatif
      Hospital between April 1994 and March 1998 for laparoscopic cholecystectomy, were
      prospectively compared for their clinical presentation, surgical management and
      long-term result. RESULTS: Both groups were comparable from the clinical
      presentation point of view as well as the operative time. The incidence of
      choledocholithiasis was higher among the sicklers, which was managed successfully
      by endoscopic retrograde cholangiopancreatograph and endoscopic sphincterotomy.
      Minor postoperative complications were more common in sicklers, but were managed
      conservatively. There was no mortality in both groups and most of the sickle cell
      patients were relieved of their symptoms of gallstones. CONCLUSION: Laparoscopic
      cholecystectomy is safe and is a beneficial surgical procedure for the management
      of cholelithiasis in patients with sickle cell anemia and not associated with
      increased major morbidity or mortality.

PMID- 11573113
TI  - Effect of sickle cell trait and B-Thalassemia minor on determinations of HbA1c by
      an immunoassay method.
AB  - OBJECTIVE: Glycated hemoglobin determination is being used worldwide to monitor
      the efficiency of blood glucose control and to plan treatment in diabetes
      mellitus patients. Several methods are used for measuring glycated hemoglobin,
      but a possible interference by hemoglobin variants is a major concern. The use of
      immunoassay methods with glycated hemoglobin-specific antibodies is supposed to
      overcome this problem. We are evaluating the effect of the most prevalent
      hemoglobinopathies in the region (sickle trait hemoglobin and B-Thalassemia) on
      the immunoassay method used in determining glycated hemoglobin. METHODS: Eighty
      one whole blood sample hemolysates were tested for glycated hemoglobin using
      Beckman Synchron LX20 system, 37 of these normal adult hemoglobin represented 22
      diabetic and 15 non-diabetic samples. Of the remaining 44 samples, 28 were from B
      thalassemia minor and 16 from sickle-cell trait sickle trait hemoglobin patients,
      all non-diabetic. The samples were collected in ethylenediaminetetraacetic acid
      anticoagulant and analyzed immediately or stored at 4?C for not more than 2 days.
      RESULTS: Sickle trait hemoglobin had no effect on glycated hemoglobin measurement
      by Synchron LX20 while B-thalassemia minor blood elevated the value of glycated
      hemoglobin to the range of diabetic cases. CONCLUSION: Synchron LX20 glycated
      hemoglobin immunoassay method gave falsely high glycated hemoglobin results with
      B-thalassemia minor patient samples. Therefore, while interpreting the results of
      Synchron LX20 glycated hemoglobin, the patients history regarding
      hemoglobinopathies should be checked.

PMID- 11573114
TI  - Efficacy of Sulphadoxine and Pyrimethamine, Doxycycline and their combination in
      the treatment of chloroquine resistant Falciparum Malaria.
AB  - OBJECTIVE: The present in vivo study evaluates the efficacy of
      sulphadoxine/pyrimethamine, doxycycline and their combination in the treatment of
      Sudanese patients infected by chloroquine resistant falciparum malaria. METHODS:
      Febrile patients with positive blood smears of Plasmodium falciparum were given
      chloroquine 25mg-base/kg body weight and followed up for 3 days. Patients with
      recrudescence due to chloroquine resistance were readmitted for test treatment.
      Using simple number randomization patients were divided into groups, A, B and C.
      These were treated with doxycycline, sulphadoxine/ pyrimethamine and a
      combination therapy of sulphadoxine/pyrimethamine plus doxycycline. Doxycycline
      was initially administered as a single dose of 200mg followed by 100mg daily for
      6 days whereas sulphadoxine/pyrimethamine was given as a single dose of
      sulphadoxine 1500mg and pyrimethamine 75mg. Patients of group C received the
      combination therapy of sulphadoxine/pyrimethamine and doxycycline. Clinical
      observations and examination of blood films were carried out for each patient
      daily for 6 days and thereafter weekly for 4 weeks. RESULTS: A high level of
      chloroquine resistance (75%) was documented amongst 280 patients (age 15-53
      years) visiting Omdurman Hospital of Endemic Diseases during 1996-1998. The study
      demonstrated that only 46% and 78% of the patients were cured after 4 days of
      treatment by doxycycline and sulphadoxine/pyrimethamine. Patients treated with
      sulphadoxine/pyrimethamine in combination with doxycycline had a cure rate of 90%
      and 100% after 3-4 days of treatment, a single recrudescent case was detected on
      day 6. No relapses occurred during the follow up period. All patients were
      successfully treated by all regimens with the exception of one case treated by
      doxycycline. All treatments were well tolerated but a few cases had complaints of
      nausea. CONCLUSION: The combination therapy of
      doxycycline/sulphadoxine/pyrimethamine appeared to be significantly effective in
      the treatment of patients with chloroquine resistant falciparum malaria without
      causing any serious side effects. Such a combination regimen has the advantages
      of being available at a reasonable cost and less prone to development of
      resistance.

PMID- 11573115
TI  - Subclinical human papillomavirus infection of the cervix.
AB  - OBJECTIVE: A prospective study to investigate a group of Iraqi woman with proved
      genital vulval warts, to seek evidence of human papillomavirus infection in
      apparently normal looking cervixes and to investigate the natural history of
      infection. METHODS: From December 1997 to August 1998, 20 women with vulval warts
      were enrolled along with 20 aged-matched control cases without warts. Their ages
      ranged between 19-48 years with a mean of 30.4 years, (+/- standard deviation =
      2.3) for patients and 18-48 years with a mean of 29.7 (+/- standard deviation =
      2.7) for the control group. General and gynecological examinations were carried
      out. Cervical swabs for associated genital infection, papilloma smears,
      speculoscopy and directed punch biopsies were carried out to detect subclinical
      human papillomavirus infections of the cervix and associated intraepithelial
      neoplasm. RESULTS: Cytology results showed that 11 (55%) of patients had evidence
      of cervical infection by human papillomavirus, 6 (30%) showed mild dysplastic
      changes, 3 (15%) showed moderate dysplastic changes, whilst 2 (10%) showed no
      dysplastic changes. Speculoscopy and acetowhitening was positive in 11 (55%) and
      collated histological results showed evidence of human papillomavirus infection
      in 9 patients (45%). As for the control group one case (5%) had evidence of human
      papillomavirus infection. CONCLUSION: Subclinical human papillomavirus infection
      is more common than was previously thought among Iraqi women. It may appear alone
      or in association with vulval or exophytic cervical warts, or both, and may be
      more common than the clinically obvious disease. Speculoscopy as an adjunctive
      method to colposcopy was found to be a simple and an easy to perform technique.
      Its combination with cytology gave relatively good results when it was used as a
      triage instrument, and may have a more promising performance in the future.

PMID- 11573116
TI  - A comparison of spontaneous labor with induced vaginal tablets prostaglandin E2
      in grand multiparae.
AB  - OBJECTIVE: To compare the outcome of labor in grandmultiparous patients (para >5)
      who had induction of labor with prostaglandin E2 vaginal tablets with
      grandmultiparous patients in spontaneous labor, and to observe the complications
      during induction of labor. METHODS: A retrospective case control study was
      carried out at King Faisal Military Hospital, Khamis Mushayt between January 1993
      through until December 1994. This included 64 grandmultiparous patients that were
      induced with prostaglandin E2 vaginal tablets. Ninety grandmultiparous patients
      who went into labor spontaneously served as controls. Maternal and fetal data
      extracted from their hospital record files included age, parity, indication for
      induction, Bishop score at induction, total dose of prostaglandin used and
      complications of induction of labor. Other information were length of labor, need
      for syntocinon augmentation, blood loss during the 3rd stage of labor, mode of
      delivery, birth weight, sex and Apgar score at 10 minutes. RESULTS: No serious
      complication of induction of labor such as rupture of the uterus was noted in the
      subjects studied. There were no significant differences when the mean age and
      parity of patients in the 2 groups were compared (P>0.05) but there was
      difference in the gestational age at delivery (p=0.00). There was no significant
      difference in the mean length of first and 2nd stages of labor. The cesarean
      section rate was 11% and 8% in the cases and controls, while the need for
      syntocinon augmentation was twice in the cases than controls, 27% vs 14%. These
      were not statistically significant. CONCLUSION: We conclude that induction of
      labor with prostaglandin E2 vaginal tablets may not have adverse effect on the
      outcome of labor compared with patients in spontaneous labor. It may be safe to
      use prostaglandin E2 vaginal tablets for induction of labor in the grand-
      multiparae. We recommend a randomized prospective trial to validate these
      observations.

PMID- 11573117
TI  - Risk factors of uterine rupture.
AB  - OBJECTIVE: To determine the incidence of uterine rupture in Ministry of Health
      Hospitals in Bahrain and to find the risk factors associated with this
      obstetrical tragedy. METHODS: A case control study was conducted on all the cases
      of uterine rupture in Ministry of Health Hospitals in Bahrain during the period
      1st of January 1990 until 31st of December 1999. The following risk factors
      which, were studied, included parity, gestational age, previous cesarean
      delivery, previous cesarean section for cephalopelvic disproportion, previous
      evacuation of the uterus, induction and or augmentation of labor,
      malpresentation, duration of the labor, type of the delivery and birth weight.
      RESULTS: Forty-five uterine ruptures were reported during the study period with
      an incidence of 1 in 2213 deliveries. Previous cesarean delivery, prior cesarean
      section for cephalopelvic disproportion, malpresentation, induction and
      augmentation of labor were found to be significant risk factors for uterine
      rupture. While high parity, previous evacuation of the uterus, duration of labor,
      type of the delivery, birth and weight were not associated with uterine rupture.
      CONCLUSION: An Obstetrician should be careful in monitoring the progress of labor
      in women with previous cesarean delivery to avoid the occurrence of a ruptured
      uterus. Oxytocin or prostaglandin or both should be used judiciously to prevent
      catastrophic uterine rupture.

PMID- 11573119
TI  - Allergic bronchopulmonary aspergillosis mimicking pulmonary Tuberculosis.
AB  - Allergic bronchopulmonary aspergillosis is an uncommon disease in which cystic
      bronchiectasis is a common feature. The presence of central bronchiectasis with
      constitutional symptoms of cough, fever, weight loss, and pulmonary infiltration
      in patients with allergic bronchopulmonary aspergillosis has been misdiagnosed as
      cavitating pulmonary tuberculosis. Herein, we report 2 cases of allergic
      bronchopulmonary aspergillosis that were misdiagnosed as pulmonary tuberculosis
      and treated with antituberculous therapy. They all have negative sputum and
      bronchoalveolar lavage for acid-fast bacillus as well as their tuberculin tests.
      The diagnosis of pulmonary tuberculosis was based on the presence of symptoms and
      radiological changes. In both cases the presence of long standing asthma, high
      peripheral eosinophilic counts and wide spread of central bronchiectasis besides
      the poor response of antituberculous therapy has drawn our attention towards the
      diagnosis of allergic bronchopulmonary aspergillosis. This was confirmed by the
      presence of high immunoglobulin E level, positive skin prick test and positive
      specific serum immunoglobulin E to aspergillus fumigatus. Therefore, a high index
      of clinical suspicion with appropriate laboratory tests is required to identify
      such cases.

PMID- 11573118
TI  - Study of colorectal cancer in Qatar.
AB  - OBJECTIVE: To study the epidemiology of colorectal cancer in Qatar and compare it
      with other parts of the world. To collect demographic data on colorectal cancer
      in Qatar (age and sex distribution) and to collect anatomic pathology data on
      colorectal cancer in Qatar. METHODS: Retrospective analysis of data collected
      from hospital records was used to review the incidence and prevalence of
      colorectal cancer in Qatar. During the period 1994-1998, one hundred and twenty
      patients with colorectal cancer were seen at Hamad General Hospital. RESULTS:
      Mean annual incidence was 24 patients/year. Forty-five patients were Qataris and
      75 were non Qataris. Of the Qatari patients 26 (58%) were males and 19 (42%)
      females, male/female ratio was 1.4:1. Nine (20%) patients were under the age of
      40 years, the presenting symptoms, physical signs and the stage of the disease
      were similar to other studies. Descending and sigmoid colon was the most common
      anatomical site affected. The most common histopathological type was
      adenocarcinoma. CONCLUSION: The overall incidence of colorectal cancer in Qatar
      is lower than most of the industrial countries, this may be due to certain
      factors such as young population, high intake of fruits and vegetables and the
      life style of the people in Qatar. The incidence in the people below the age of
      40 years is higher than industrial countries and, in males due to the demographic
      structure of the population in Qatar.

PMID- 11573120
TI  - Delayed presentation of traumatic rupture of the diaphragm.
AB  - Diaphragmatic injuries occur frequently after penetrating rather than blunt
      trauma and account for 8% of all organ injuries from penetrating trauma. Motor
      vehicle accidents account for approximately 50% of blunt injuries, followed in
      frequency by falls from height. The mechanism of injury in these accidents is
      that the body quickly decelerates while the organs continue to move downward or
      forward at maximal velocity, tearing vessels and tissues from their points of
      attachment. In this paper we are presenting 3 cases of traumatic diaphragmatic
      rupture due to motor vehicle accidents and fall from height, in which the
      diagnosis was delayed. Patient one was initially diagnosed with hemorrhagic
      pleural fluid for investigation, patient 2 was diagnosed 4 months later and
      patient 3 presented 7 years after the initial trauma. All were successfully
      treated surgically once the diagnosis was established.

PMID- 11573121
TI  - Ear, nose and throat manifestations of relapsing polychondritis in a child.
AB  - Relapsing polychondritis is a rare disorder, that can present initially to
      Otolaryngologists and can easily be overlooked due to its relative rarity and
      atypical initial symptoms and signs. Here we report on a 12-year-old schoolboy
      who presented initially with ear, nose and throat manifestations, including
      stridor, cough, hoarseness, sore throat and fever. The other clinical signs such
      as nasal tip, depression and softening of right auricle, developed subsequently.
      The clinical features, laboratory investigations, diagnostic criteria and
      treatment options were discussed with a brief review of literature.

PMID- 11573122
TI  - Salmonella food poisoning in Najran.

PMID- 11573123
TI  - Is the pancreas responsible for Hyperemens Gravidarum?

PMID- 11573124
TI  - [Preoxygenation - a must! But which is the best technique to use?].

PMID- 11573125
TI  - [Perioperative antiarrhythmic drug management].
AB  - Perioperative arrhythmias are common. In 2.5 % they result in a severe adverse
      outcome. This review discusses the normal physiology of the myocardial conduction
      system and the etiology and pathophysiology of the most common perioperative
      dysrhythmias. Subsequently some important antiarrhythmic drugs are described and
      treatment plans for the most frequent dysrhythmias are presented.

PMID- 11573126
TI  - [Do baseline haemoglobin-rates point to the efficacy of blood saving
      techniques?].
AB  - OBJECTIVE: We tested the hypothesis that blood saving techniques are more
      effective in patients with a low baseline haemoglobin. METHODS: We analysed
      retrospectively 1665 total hip replacements and 848 total knee replacements.
      Patients were divided in three groups according to the baseline haemoglobin (Hb):
      Group A were patients with a Hb of more than 15 g/dl, group B between 15 g/dl and
      13 g/dl and group C with a Hb of less than 13 g/dl. The blood saving techniques
      applied (Preoperative blood donation, isovolemic haemodilution, and mechanical
      autotransfusion) aimed to a high patient population which underwent surgery
      without transfusion of homologous blood. RESULTS: The higher the baseline value
      of haemoglobin the higher was the patient population without homologous blood
      transfusion. The lower the Hb the higher was the effectiveness of blood saving
      techniques. In case of total hip replacement preoperative blood donation
      increased the patient population without homologous blood transfusion in all
      three groups significantly. However, in case of total knee replacement
      preoperative blood donation increased the patient population without homologous
      blood transfusion only in group B and C significantly. In both surgical
      procedures the combination of preoperative blood donation with other blood saving
      techniques did not further increase the patient population without homologous
      blood transfusion. In total hip replacement mechanical autotransfusion as well as
      isovolemic haemodilution reduced homologous transfusion in patients with low
      baseline haemoglobin. However, the increase was more pronounced when both
      techniques were combined. CONCLUSION: From our data is derived that the
      likelihood of homologous blood transfusion is greater in patients with a low
      baseline haemoglobin. However, in case of hip arthroplasty patients with a high
      baseline haemoglobin also profit from blood saving techniques while in case of
      knee arthroplasty the efficiency of blood saving techniques in a patient
      population with a high baseline haemoglobin is negligible. It seems to make sense
      to evaluate for the different kinds of surgery those patients who profit most
      from the different blood saving techniques.

PMID- 11573127
TI  - [Acceptance of preoxygenation in clinical routine by patients and by
      anaesthesiologists].
AB  - Preoxygenation is a simple technique to expand the time under planned apnea till
      the patient is endangered by hypoxia. In this study, we analysed how
      preoxygenation is used by anaesthesiologists in clinical routine and how this
      method is tolerated by the patients. One hundred and twenty-one
      anaesthesiologists of 4 hospitals were interviewed anonymously about training
      level, rank, indication for preoxygenation and techniques of preoxygenation, as
      well as their estimation of the patients' discomfort during preoxygenation. Data
      on 100 patients about oxygen-mask-tolerance were acquired by an anonymous
      questionnaire from a standard quality control inquiry. We received back 76 of the
      121 questionnaires of anaesthesiologists (63 %). Fifty-nine percent of the
      anaesthesiologists (45/76) preoxygenated in clinical routine. With increasing
      training time and higher ranks, less anaesthesiologists preoxygenated routinely:
      junior residents: 80 %; senior residents: 68 %; consultants: 60 %; assistant
      medical directors: 48 %.80 % of the anaesthesiologists (61/76) used imperfect
      techniques for preoxygenation (e. g. oxygen-flow < 8 l/min). At the time of
      preoperative evaluation, the patients estimated the discomfort during
      preoxygenation on a continuous scale (1 to 10) as 2 (median; 1 - 7: 95 %
      confidence interval). Postoperatively, the patients mentioned no discomfort: 1 (1
      - 1). The anaesthesiologists overestimated their patients' discomfort
      significantly with 5 (3 - 7) (p < 0.001).In conclusion, preoxygenation, a simple
      safety procedure, is not routinely used by many anaesthesiologists and imperfect
      methods are often employed. A possible reason for the anaesthesiologists'
      reluctance to preoxygenate is an overestimation of the patients' discomfort,
      though the patients tolerate preoxygenation very well.

PMID- 11573128
TI  - [Inhalation anesthesia].

PMID- 11573129
TI  - [Frozen shoulder--MRI-verified continuous block of suprascapular nerve].
AB  - Suprascapular nerve block may provide sufficient analgesia in painful
      immobilisation of the shoulder joint. In the following case report a 41 year old
      male presenting with adhesive capsulitis (frozen shoulder) has been treated
      successfully by performing continuous delivery of local anesthetics to the
      suprascapular nerve via catheter. The location of the catheter has been verified
      using MRI examination. Pain relief was quantified by using visual analog scale
      (VAS 1 - 10) and showed decretion from VAS 8 - 10 pre treatment to VAS 1 - 2
      after insertion of the catheter and throughout five days of intensive
      physiotherapy, respectively. The technique of catheterization using a nerve
      stimulator and alternative peripheral nerve blocks are discussed. In summary,
      continuous suprascapular nerve block offers an advantageous alternative for pain
      relief in patients with frozen shoulder. It may provide better pain control and
      earlier discharge in the ambulatory setting than repetetive single dose blocks.

PMID- 11573130
TI  - Representative data of iodine intake and urinary excretion in Germany.
AB  - To evaluate the iodine supply of the German population, 2500 representative
      subjects older than 13 years were elected for answering a specific food
      questionnaire. In addition spot urine samples in 3 selected risk groups for
      iodine deficiency (574 adults aged 50-70 years, 769 conscripts, 886 pairs of
      mothers and newborns) from 26 representative regions were collected. Furthermore
      the circadian iodine excretion was measured in 24 h urine samples collected in 6
      fractions per day in 4 subgroups (young and older males and females) of 91
      controls and this 24 h iodine excretion related to iodine/creatinine ratio in
      these subgroups. Mean estimated iodine intake was 119 microg/d in adults aged 50
      70 years, 137 microg/d in conscripts, and 162 microg/d in mothers at still birth.
      The mean iodine concentration (iodine/creatinine ratio) was 9.4 microg/dl in 566
      adults aged 50-70 years, 8.3 microg/dl in 772 conscripts and 5.6 microg/dl in 739
      breast fed newborns. The mean daily iodine excretion was 134 microg/d in 278 men
      aged 50-70 years, 117 microg/d in 288 women aged 50-70 years, 125 microg/d in 772
      conscripts and 74 microg/d in 53 breast-feeding mothers not using iodine tablets.
      These results show, that iodine intake in Germany has increased over the last
      years. The deficit in iodine intake with significant regional differences and
      defined risk groups for iodine deficiency (e.g. breast feeding mothers without
      iodine deficiency prophylaxis) is estimated to be about 30% of the recommended
      iodine intake.

PMID- 11573131
TI  - Thyroid volumes and urinary iodine in German school children.
AB  - Several recently published investigations showed a significant improvement in the
      iodine supply of the German population, but so far Germany is still considered an
      iodine deficient country. However most of the studies presented do not meet the
      epidemiological criteria established by WHO, UNICEF and ICCIDD and may therefore
      suffer from a selection bias with respect to goiter prevalence estimates. School
      children, owing to their easy recruitment, representativeness of different socio
      economic classes and high vulnerability of Iodine deficiency disorders (IDD), are
      one of the best target groups for surveillance of IDD. In this field study a
      total of 591 children were investigated. The total sample included 268 females
      and 323 males aged 7-17 years. The following data were collected: thyroid size by
      ultrasound, urinary iodine concentration in a first-morning spot urine, weight,
      height, sex and age. The median urinary iodine concentration of the children was
      183 microg/L. The proportion of samples with concentrations below 100 microg/L or
      below 50 microg/L was 15.4% and 4.3% respectively. Urine samples with high iodine
      concentrations were also found amounting to 17.3%. Almost all families (97%)
      declared to use iodized kitchen salt and 19.6% of all children are taking
      regularly iodine tablets. Application of the WHO/ICCIDD thyroid volume references
      to the German children resulted in a goiter prevalence of 0.2%, using either
      age/sex-specific or body surface area (BSA)/sex-specific cut-off values.
      Comparison with the P97 values of the original normative data of Gutekunst and
      Martin-Teichert however gives a goiter prevalence of 3% as expected. The thyroid
      volumes of the children in our study appear comparable with those reported
      recently for iodine sufficient children from Switzerland and for iodine replete
      Berlin children and for children with sufficient iodine supply in the region of
      Leipzig, so that Germany probably has no longer to be considered an iodine
      deficient country. Our own study and the most recently published studies on
      iodine replete children give rise to the supposition that the WHO/ICCIDD
      recommended thyroid volume references are too high.

PMID- 11573132
TI  - Iodide handling by the thyroid epithelial cell.
AB  - Iodination of thyroglobulin, the key event in the synthesis of thyroid hormone,
      is an extracellular process that takes place inside the thyroid follicles at the
      apical membrane surface that faces the follicular lumen. The supply of iodide
      involves two steps of TSH-regulated transport, basolateral uptake and apical
      efflux, that imprint the polarized phenotype of the thyroid cell. Iodide uptake
      is generated by the sodium/iodide symporter present in the basolateral plasma
      membrane. A candidate for the apical iodide-permeating mechanism is pendrin, a
      chloride/iodide transporting protein recently identified in the apical membrane.
      In physiological conditions, transepithelial iodide transport occurs without
      intracellular iodination, despite the presence of large amounts of thyroglobulin
      and thyroperoxidase inside the cells. The reason is that hydrogen peroxide,
      serving as electron acceptor in iodide-protein binding and normally produced at
      the apical cell surface, is rapidly degraded by cytosolic glutathione peroxidase
      once it enters the cells. Iodinated thyroglobulin in the lumen stores not only
      thyroid hormone but iodine incorporated in iodotyrosine residues as well. After
      endocytic uptake and degradation of thyroglobulin, intracellular deiodination
      provides a mechanism for recycling of iodide to participate in the synthesis of
      new thyroid hormone at the apical cell surface.

PMID- 11573133
TI  - The role of pendrin in iodide regulation.
AB  - Recent advances in human genetics have catalyzed the attention on Pendred's
      syndrome and its disease-gene, PDS. Studies on the expression of the PDS gene and
      on the function of its encoded protein, which has been named pendrin, are
      currently in progress. Consistent with the Pendred's syndrome phenotype, which is
      characterized by thyroid dysfunction associated to deafness, PDS expression has
      been demonstrated in the thyroid and in the inner ear. Despite its high homology
      to known sulfate transporters, pendrin has been shown to transport iodide and
      chloride, but not sulfate. Thus, it is probably devoted to regulate, at the
      apical membrane where it has been immunolocalized, the flux of iodide from the
      thyroid cell to the colloid space. The function of pendrin in the inner ear is
      not well understood, but it seems to function also at this level as an anion
      transporter. Indeed, a pronounced PDS expression has been detected in structures
      of the inner ear, such as the membranous labyrinth and the endolymphatic duct and
      sac. At this level, the possible role of pendrin could be the maintenance of the
      appropriate ionic composition of the endolymph. Although many questions remain to
      be answered, these recent achievements concerning the putative role of pendrin
      aid to better understand the genetic basis of the peculiar phenotype of Pendred's
      syndrome, which associate the dysfunction of two so different organs such as the
      thyroid and the inner ear.

PMID- 11573134
TI  - Characterization of the upstream enhancer of the rat sodium/iodide symporter
      gene.
AB  - We previously demonstrated the presence of an enhancer that is located between
      nucleotides - 2264 and - 2495 in the 5' flanking region of the rat sodium/iodide
      symporter (NIS) gene (Ohno et al., 1999). When attached to NIS or heterologous
      promoters, this 232 bp fragment, which we call NUE, is able to stimulate
      transcription in a thyroid-specific and cAMP-dependent manner. A paired-domain
      transcription factor Pax8 binds to this enhancer and can stimulate the
      transcription in non-thyroid cells that do not normally support the NUE
      activities. Cotransfection of PKA, a downstream effector of cAMP, further
      potentiates the Pax8-mediated transactivation. However, this transcriptional
      machinery containing pax8 seems to require contributions from the neighboring cis
      acting element that is similar to CRE/AP-1 consensus sequences. Modification of
      this putative CRE/AP-1 site not only represses the NUE transcriptional activities
      by 90% in FRTL-5 cells, but also nullifies the synergistic effect of PKA on pax8
      mediated transactivation in HeLa cells. In this report, we have further
      characterized the putative CRE/AP-1 site within the NIS upstream enhancer using
      gel mobility shift assay. An oligonucleotide probe with NIS CRE/AP-1 sequence
      produced complex binding patterns in both FRTL-5 and HeLa cell, reflecting the
      presence of diverse classes of binding factors. When compared with CRE or AP-1
      elements in other genes, the mobility shift pattern of NIS CRE/AP-1 was similar
      to those of collagenase TRE, c-Jun TRE, and somatostatin CRE, but the relative
      intensities of the binding complexes were quite different. This observation
      raises a possibility that the NIS CRE/AP-site is regulated by a novel mechanism.

PMID- 11573135
TI  - Transcriptional regulation of the human sodium/iodide symporter gene by Pax8 and
      TTF-1.
AB  - The regulation of the human Na(+)/I(-) symporter (NIS) gene is of considerable
      interest for both the diagnosis and therapy of thyroid pathologies. We
      investigated the influence of the thyroid-specific transcription factors TTF-1
      and Pax8 on the NIS promoter and its 5'-flanking sequence. Reporter genes
      containing the corresponding genomic fragments coupled to a luciferase reporter
      gene were cotransfected with expression vectors carrying the the cDNA's for TTF-1
      and Pax8. Transient transfection assays were performed in HeLa and COS-7 cells,
      which do not express endogenously these transcription factors. The experiments
      showed, that TTF-1 had no influence on the NIS promoter. Pax8, on the other hand,
      had a moderate stimulating effect (threefold) on the proximal NIS promoter. ABCD
      assays indicated an interaction of in vitro-translated Pax8 with the NIS
      promoter. However, DNase I footprinting experiments with bacterially expressed
      Pax8 were negative, suggesting an indirect mode of action with the participation
      of other proteins. A putative NIS upstream enhancer (NUE) 9000 bp upstream of the
      NIS gene, which was cloned based on its sequence homology to the rat NUE, was not
      transactivated by either Pax8 or TTF-1. The present data demonstrate, that the
      combination of Pax8 and TTF-1 is less important for NIS gene transcription than
      for other thyroid-specific genes. This is presumably related to the fact, that
      NIS is expressed also in other tissues such as mammary and salivary gland.

PMID- 11573136
TI  - Sodium/iodide symporter (NIS) and cytokines.
AB  - It has been shown that TSH upregulates rat NIS gene expression in vitro, and this
      induction can be modulated by cytokines. Analysis of the distribution of rat NIS
      mRNA ex vivo demonstrated variable levels of NIS transcription in different
      tissue samples. - IL-1beta and IL-6 have been found to decrease NIS mRNA
      expression in TSH-stimulated FRTL-5-cells. IL-6 has no effect on NIS functional
      activity, whereas IL-1beta suppresses iodide accumulation. The NIS is expressed
      in thyroid tissue of patients with autoimmune thyroid diseases, and its
      expression is increased in Graves' disease. With respect to other thyroidal
      autoantigens such as TPO and Tg, NIS obviously shows a very similar pattern to
      the well-described antigenic targets and may participate as an autoantigen in
      these diseases. Up to now only data of in vitro studies are available which
      started to evaluate the effects of different cytokines on NIS expression. The
      mechanisms of NIS regulation with respect to cytokine modulation in thyroid
      autoimmune disease remain still unproven and data of experimental in vivo studies
      and clinical trials in patients with thyroid autoimmune disease have to further
      elucidate these open questions in the future.

PMID- 11573137
TI  - Autoimmunity involving the human sodium/iodide symporter: fact or fiction?
AB  - Presence, functional activity and clinical relevance of autoantibodies directed
      against the human sodium iodide symporter (NIS) in thyroid autoimmune diseases
      have become the subject of much controversy in recent years. Earlier reports have
      claimed that NIS may represent a major thyroid autoantigen that elicits formation
      of functionally relevant autoantibodies in a significant proportion of patients
      with Graves' disease (GD) and Hashimoto's thyroiditis (HT). Moreover, a recent
      study has extended this notion by reporting detection of NIS-autoantibodies in
      22% and 24% of a small number of patients with GD and HT, respectively, but not
      in patients with other autoimmune diseases. However, in striking contrast to
      these reports, two independent groups of investigators have now presented
      convincing evidence that NIS-directed autoantibodies occur with low frequency
      among a large sample of patients with autoimmune thyroid diseases. Moreover, no
      evidence of specific iodide uptake inhibiting activity was obtained once sera had
      been subjected to dialysis and/or IgG extraction. Thus, although the controversy
      has not been definitively resolved, hNIS does not appear to be a major
      functionally relevant antigen in autoimmune thyroid diseases. Moreover, when
      detected in addition to TPO and TSH receptor autoantibodies, NIS-directed
      autoantibodies do not appear to contribute any diagnostic power for GD and HT.

PMID- 11573138
TI  - Regulation of the sodium/iodide symporter by retinoids--a review.
AB  - Decrease or loss of iodide uptake, due to impaired expression and/or function of
      the sodium/iodide-symporter (NIS), is a major obstacle to the treatment of
      advanced thyroid carcinomas by radioiodide therapy. Several approaches are being
      evaluated to optimise or restore sufficient iodide transport in those cases,
      among them retinoid therapy. Retinoids with their growth-inhibiting and
      differentiation-inducing properties have been repeatedly used for treatment and
      chemoprevention of various cancers. In thyroid carcinoma cell lines they trigger
      changes in gene expression that may be interpreted as partial redifferentiation.
      Especially, they stimulate NIS mRNA expression and iodide uptake in human
      follicular thyroid carcinoma cells. Moreover, they also increase NIS expression
      and function in human mammary tumour cells. In a clinical pilot study to evaluate
      the feasibility of retinoid redifferentiation in the case of otherwise
      untreatable thyroid cancers, 21 of 50 patients showed an increase of radioiodide
      uptake after 5 weeks. This indicates that increasing NIS activity and radioiodide
      uptake by retinoic acid redifferentiation may be a therapeutic alternative for
      thyroid cancers refractory to other therapeutic modalities and probably also for
      mammary cancer.

PMID- 11573139
TI  - Sodium/iodide symporter mRNA expression in cold thyroid nodules.
AB  - Clinical and experimental data suggest a low thyroid hormone synthesis in cold
      thyroid nodules (CTN). Therefore, the Na(+)/I(-)-symporter (NIS) as the first
      step in the thyroid hormone synthesis could be a possible candidate gene in the
      pathogenesis of CTNs. A reduction of NIS transcripts in CTNs compared to samples
      of normal thyroid tissues with large inter-individual variations ranging from 2-
      to 700-fold reductions was observed with real-time RT-PCR. Therefore, the aim of
      our investigations was to perform an intra-individual comparison of NIS
      expression in CTNs. Moreover, we used direct detection of NIS mRNA by RNase
      protection assay (RPA). We investigated 14 patients with one CTN for NIS mRNA
      expression. NIS mRNA transcripts from nodule and surrounding tissue were examined
      by RPA. A significantly reduced NIS expression was detected in 86% of the CTNs
      compared to their corresponding surrounding tissue. The level of NIS expression
      was decreased to more than 65% in 10 CTNs (72% of the nodules). Two of the 14
      nodules showed a decrease of NIS mRNA expression of 42%, and 32%, while no
      significant differences could be detected in 2 cold nodules. Compared to other
      studies the intra-individual comparison of NIS mRNA expression revealed a much
      lower variation of reduced NIS expression in CTNs. Further studies should try to
      identify molecular factors like post-transcriptional modifications or alterations
      in iodide organification which are likely to be involved in the pathogenesis of
      CTNs.

PMID- 11573140
TI  - Sodium/iodide symporter in thyroid cancer.

PMID- 11573141
TI  - Expression of the human sodium/iodide symporter (hNIS) in xenotransplanted human
      thyroid carcinoma.
AB  - The uptake of iodide in thyroid epithelial cells is mediated by the sodium/iodide
      symporter (NIS). The uptake of iodide is of vital importance for thyroid
      physiology and is a prerequisite for radioiodine therapy in thyroid cancer. Loss
      of iodide uptake due to diminished expression of the human NIS (hNIS) is
      frequently observed in metastasized thyroid cancer. So far, no animal model for
      the study of radioiodine therapy in thyroid cancer has been available. Strategies
      to restore iodide uptake in thyroid cancer include the exploration of hNIS gene
      transfer into hNIS defective thyroid cancer. We have performed a stable
      transfection of hNIS into the hNIS defective follicular thyroid carcinoma cell
      line FTC133. Stably transfected colonies exhibited high uptake of Na125I, which
      could be blocked completely with sodium perchlorate. hNIS transfected FTC133 and
      non-transfected cell lines injected subcutaneously in nude mice formed tumors
      after 6 weeks. Iodide uptake in the hNIS transfected tumor was much higher than
      in non-transfected tumor, but a rapid release of radioactivity from the hNIS
      transfected tumor was observed. Further studies are necessary to investigate the
      role of hNIS in relation to other thyroid specific proteins in iodide metabolism
      in thyroid cancer.

PMID- 11573142
TI  - Approaches to gene therapy with sodium/iodide symporter.
AB  - Since cloning and characterization of the sodium iodide symporter (NIS) gene,
      several investigators explored the possibility of a novel cytoreductive gene
      therapy strategy based on NIS gene transfer into non-thyroidal tumor cells
      followed by radioiodine therapy. NIS gene transfer has been shown to be capable
      of inducing radioiodine accumulation in vitro and in vivo in several non
      thyroidal cancer cell lines. Following PSA promoter-mediated NIS gene delivery we
      were able to demonstrate prostate-specific iodide accumulation in prostate cancer
      cells that was high enough to elicit a therapeutic response of 131-I in vitro and
      in vivo. This study clearly demonstrates the potential of NIS as a novel
      therapeutic gene for non-thyroidal cancers, in particular prostate cancer.

PMID- 11573143
TI  - Gene therapy with sodium/iodide symporter in hepatocarcinoma.
AB  - The ability of thyroid cells to accumulate iodide is a prerequisite for
      successful radioiodide therapy of benign thyroid diseases and differentiated
      thyroid carcinoma. The transport of iodide across the cell membrane is mediated
      by the sodium iodide symporter (hNIS). Employing a bicistronic retroviral vector
      for the transfer of the hNIS coding sequence and the hygromycin resistance gene
      stable hNIS expressing rat Morris hepatoma (MH3924A) cell lines were generated by
      hygromycin selection. Genetically modified MH3924A cell lines accumulated up to
      235 times more iodide when compared to non-infected hepatoma cells with a maximal
      iodide uptake after 60 minutes incubation. Competition experiments in the
      presence of sodium perchlorate revealed a dose dependent decrease of the iodide
      uptake, FCCP led to a loss of accumulated I(-), whereas DIDS increased the I(-)
      uptake into the cells. However, a rapid efflux of the radioactivity (80%) was
      observed during the first 10 minutes after the 125I(-) containing medium had been
      replaced by non-radioactive medium. In rats, the hNIS-expressing tumors
      accumulated six times more iodide as compared to the contralateral wild type
      tumor as monitored by scintigraphy. An ex vivo quantitation of the iodide content
      performed 1 hour after tracer administration in 1g tumor tissue revealed a 17
      fold higher iodide accumulation in the genetically modified tumors. In vivo also
      a rapid efflux of the radioactivity out of the tumor was observed. Therefore, the
      transduction of the hNIS gene per se is sufficient to induce 125I(-) transport in
      Morris hepatoma cells in vitro and in vivo. For a therapeutic application of the
      hNIS gene, however, additional conditions need to be defined which inhibit the
      iodide efflux.

PMID- 11573144
TI  - Insulin analogues: impact of cell model characteristics on results and
      conclusions regarding mitogenic properties.

PMID- 11573145
TI  - Insulin secretion and anti-GAD65 antibodies in subjects with impaired glucose
      tolerance.
AB  - The study was designed to evaluate the pattern of insulin secretion and the
      presence of anti-GAD65 antibodies as beta-cell autoimmune marker in subjects with
      impaired glucose tolerance (IGT) and their impact on the further development of
      glucose intolerance. 29 subjects with IGT, of mean BMI 24.7 +/- 2.4 kg/m(2) and
      mean age 37.7 +/- 7.0 years were enrolled in the study. They were followed-up
      once yearly for three years. A group of 59 age- and weight-matched subjects with
      normal glucose tolerance (NGT) served as a control group. 42 newly-diagnosed
      diabetic patients, of mean BMI 24.4 +/- 2.7 kg/m(2) and mean age 37.2 +/- 6.9
      years were also studied. According to their response during IVGTT the subjects
      with IGT were divided into two groups. The first group (n = 11)(IGT-I) showed
      reduced FPIS (34.0 +/- 8.9 mU/l vs 114.4 +/- 41.2, p < 0.001), SPIS being within
      normal values, and reduced AUC for total insulin secretion (1554.1 +/- 496.3 vs
      2323.6 +/- 804.5 mU/l x 60 min, p < 0.001); the difference with type 1 diabetic
      patients being significant (p < 0.001), the pattern of insulin secretion being
      quite similar to that of type 2 diabetic patients. The other group (n = 18) (IGT
      II) demonstrated normal insulin secretion (FPIS, SPIS, AUC for insulin
      secretion), not differing from that of the controls with NGT. Anti-GAD65 were
      present in 3.3% of subjects with NGT, in 73.7% of patients with type 1 diabetes
      and in none of type 2 diabetic patients. 18% from the group with IGT-I were anti
      GAD65 positive, and 22% - from IGT-II. 5 of the subjects with IGT-I developed
      diabetes during the follow-up period - 2 at the 1st year, 1 at the 2nd year and 2
      - at the third year. One of these patients was anti-GAD65 positive (having the
      highest anti-GAD65 level amongst the others with IGT - 15.2 U/ml), showing
      pattern of insulin secretion similar to that of type 1 diabetic patients. 3 of
      the subjects with IGT-II reverted to NGT within the first year and 2 - at the
      second year, none of them being anti-GAD65 positive. The anti-GAD65 positive
      patients from this group remained with IGT, and none progressed to diabetes
      mellitus. We consider that IVGTT allows precise assessment of the phases of
      insulin secretion and in combination with the study of anti-GAD65 antibodies
      helps to identify the subjects with IGT at risk of developing diabetes mellitus.
      As far as the decrease in the FPIS is considered it could be proposed that such
      subjects are assigned to certain protective measures - diet, physical activity
      and some drugs affecting postprandial glucose levels.

PMID- 11573146
TI  - Association of the mitochondrial DNA 5178A/C polymorphism with maternal
      inheritance and onset of type 2 diabetes in Japanese patients.
AB  - The mitochondrial DNA 5178A/C (mt5178A/C) polymorphism is associated with
      longevity and adult onset diseases. We investigated an association of the
      mt5178A/C polymorphism with the occurrence and clinical features of type 2
      diabetes. Two hundred and seventy Japanese patients with type 2 diabetes (181 men
      and 89 women) and 254 control subjects without diabetes were studied. Patients
      with mutations at position 3243 in the mitochondrial DNA were excluded. Genotype
      was determined by the polymerase chain reaction-restriction fragment length
      polymorphism method. Various clinical features including age at disease onset
      were compared between the patients with the mt5178A and mt5178C alleles. Mt5178C
      was observed more frequently in patients with type 2 diabetes than in control
      subjects (65.9% vs 57.9%, P = 0.058). Clear information about the maternal
      history of diabetes was obtained from 233 diabetic patients. Patients with a
      maternal history of diabetes carried the mt5178C allele (58/75, 77.3%) more
      frequently than did patients without a maternal history of diabetes (100/158,
      63.3%; P = 0.032) and control subjects (57.9%; P = 0.002). The mean age at onset
      of diabetes was significantly lower in patients with mt5178C (47.6 +/- 11.4
      years) than in patients with mt5178A (51.5 +/- 10.0 years; P = 0.0073). The
      mt5178A/C polymorphism may be associated with maternal inheritance of type 2
      diabetes and may influence the age at onset through deterioration of
      mitochondrial function.

PMID- 11573147
TI  - Low levels of Sex-Hormone-Binding Globulin predict insulin requirement in
      patients with gestational diabetes mellitus.
AB  - Low Sex-Hormone-Binding Globulin (SHBG) levels--indicating a state of
      hyperandrogenicity--are associated with a higher risk for the development of non
      insulin dependent diabetes (NIDDM) in women and are accepted as a marker of
      muscular insulin resistance. To analyze whether low SHBG values are also present
      in patients with gestational diabetes, we investigated levels of SHBG in 42
      patients with gestational diabetes mellitus (GDM) in comparison with 48 pregnant
      women with normal glucose tolerance (NGT). Beside maternal parameters like body
      mass index (BMI), HbA1c, fasting, 1- and 2-hour blood glucose and insulin
      concentrations, parameters of the new-borns (head-circumference, body weight,
      height and sex) were recorded. Maternal and neonatal variables were then related
      to SHBG levels. Both groups showed no differences in BMI, height, weight or age
      of gestation. Patients with GDM revealed significantly lower levels of SHBG than
      pregnant women with NGT(512 +/- 249 nmol/l vs. 643 +/- 137 nmol/l; p < 0.01). In
      patients with severe GDM and insulin therapy significantly lower levels of SHBG
      than in those with dietary treatment only were found (223 +/- 210 nmol/l vs. 592
      +/- 102 nmol/l; p < 0.001). SHBG was inversely correlated to BMI (r = - 0.30; p <
      0.01), 1-hour (r = - 0.20; p < 0.05) and 2-hour blood glucose levels (r = - 0.30;
      p <0.01). In summary, we found significantly lower levels of SHBG in patients
      with GDM, especially in those who developed severe GDM and required insulin
      therapy during the last months of pregnancy.

PMID- 11573148
TI  - Interrelationship between plasma leptin concentration and severity of metabolic
      acidosis in haemodialysed patients with chronical renal failure.
AB  - Patients with chronic renal failure are frequently characterized by malnutrition,
      hyperleptinaemia and metabolic acidosis. Both hyperleptinaemia and chronic
      metabolic acidosis are presumed to contribute to the pathogenesis of malnutrition
      observed in this group of patients. It has been reported, that in vitro
      adipocytes exposed to acidotic medium decrease leptin secretion. The aim of
      present study was to analyze the possible impact of uraemic metabolic acidosis on
      leptinaemia in haemodialysis patients with chronic renal failure. - 94
      haemodialysed patients (58 M, 36 F; mean age 45 +/- 1 years) were enrolled in
      this study. 56 patients were on haemodialysis treatment for one year using an
      acetate dialysis fluid, while 38 patients were haemodialysed at least for 3
      months with a dialysate buffered with bicarbonate. Plasma leptin concentration,
      blood gases and body composition were assessed in all examined subjects. -
      Patients haemodialysed with an acetate and bicarbonate buffered dialysate did not
      differ with respect to body weight, body mass index (BMI), total fat mass (TFM)
      and plasma leptin concentration. Patients haemodialysed with an acetate buffered
      dialysate were characterized by a significantly more severe metabolic acidosis
      than patients on bicarbonate haemodialysis. Patients were divided according to
      the actual hydrogen ion concentration: over 60 nmol/l, 45-60 nmol/l and below 45
      nmol/l. These subgroups did not differ significantly by body weight, BMI and TFM.
      Only a slightly (not significantly), lower median leptinaemia was found in
      patients with elevated hydrogen ion concentration. No significant correlation was
      noticed between blood hydrogen or hydrocarbonate ion concentration respectively
      and logarithmic values of plasma leptin concentration (tau = 0.025, p = 0.72; tau
      = - 0.021, p = 0.76 respectively). - From results obtained in this study we may
      conclude that, blood hydrogen ion concentration does not influence substantially
      or only moderately to plasma leptin concentration in haemodialysed patients.

PMID- 11573149
TI  - Activities of 11beta-hydroxysteroid dehydrogenase 2 in different regions of the
      intestinal tract of pigs.
AB  - 11beta-Hydroxysteroid dehydrogenase 2 (11beta-HSD 2) converts active cortisol to
      inactive cortisone and thus modifies the availability of glucocorticoids for the
      target tissue. An additional function is the protection of the aldosterone
      receptor in mineralocorticoid-sensitive tissues such as the kidney and the gut.
      The occurrence of 11beta-HSD 2 activity was investigated in several species. Data
      for the pig, however, so far are missing. The activity was determined by a radio
      enzyme-assay based on the conversion of tritiated cortisol to cortisone under
      standardized incubation conditions in supernatants of homogenates prepared from
      tissues of four castrates. Tissues comprised several locations along the
      intestinal tract and in addition kidney, lung, muscle, heart, spleen and
      pancreas. Highest values of the enzyme activity were found in kidney and very low
      activities in lung tissue but no activity in muscle, spleen, heart and pancreas.
      In the gut, there was a continuous increase in enzyme activity from the duodenum
      (0.60 pmol x min(- 1) x mg protein(- 1)) towards the colon with maximum values in
      the colon transversum (23.32 pmol x min(- 1) x mg protein(- 1)). In the colon the
      activity was 10-fold higher than in jejunum and 3-fold higher compared to ileum.
      The activities did not differ significantly between the colon transversum and
      colon descendens.

PMID- 11573150
TI  - Pancreatic neuroendocrine tumor with extensive vascularisation and parathyroid
      hormone-related protein (PTHrP)--associated hypercalcemia of malignancy.
AB  - We report the case of a 34 year old male presenting with symptomatic
      hypercalcemia due to excessive PTHrP secretion from a pancreatic neuroendocrine
      carcinoma with extensive hypervascularization and without any evidence for
      metastatic disease. In the early phase of the disease conventional chemotherapy
      with streptozocin and doxorubicin was able to control functional activity as well
      as tumor growth. However, after 2 years tumor escape was indicated by severe
      therapy-resistant hypercalcemia. Therapeutic options were reduced due to the
      excessive tumor vascularization and the patient died from his disease after a
      short period of intensified therapy. The role of PTHrP in hypercalcemia of
      malignancy (HHM) and its association with neuroendocrine pancreatic tumors as
      well as possible therapeutic options are reviewed.

PMID- 11573151
TI  - Clinical features of a polymorphism of the beta3-adrenergic receptor gene in
      patients with type 2 diabetes mellitus--a study using a pin-point sequencing
      method.
AB  - The human beta(3)-adrenergic receptor (beta(3)AR) is expressed specifically in
      adipose tissues, and its activation is activated in brown adipose tissues during
      thermogenesis and in white adipose tissues during lipolysis. We investigated the
      relationship between a polymorphism of the beta(3)AR gene and the clinical
      features of type 2 diabetes mellitus. Studies were conducted in 30 type 2
      diabetic patients (15 males and 15 females). Analysis of polymorphisms of the
      beta(3)AR gene was performed by a pin-point sequencing method using the hair of
      the subjects. Preperitoneal (P-fat) and subcutaneous fat (S-fat) levels were
      determined by ultrasonography. We found a Trp(64)Arg allele of the beta(3)AR gene
      in the hair of 27% of all patients. The patients with this mutation showed a
      significantly younger onset-age of diabetes than those of the wild type. The body
      mass index, serum GPT levels, fasting immunoreactive insulin (IRI) and daily
      urinary C-peptide reaction (CPR) in the mutation group were markedly higher than
      in the wild type group. The P-fat, serum cholesterol and leptin concentrations
      tended to be higher in the mutation group. Patients in the mutation group had a
      significantly higher prevalence of hypertension (80%) compared with those in the
      wild type group (20%). CONCLUSIONS: The present results suggest that the clinical
      features of diabetic patients with a missense mutation in the beta(3)AR gene are
      substantially distinct from those of the wild type patients. These specific
      features include obesity, hyperinsulinemia, hypertension, and an increase in
      preperitoneal fat.

PMID- 11573152
TI  - [Influence of surgery-related factors on the Nd:YAG laser capsulotomy rates of 3
      piece silicone IOLs - analysis of 457 pseudophakic human globes obtained post
      mortem].
AB  - BACKGROUND: The purpose of this study was to analyze any possible surgical
      reasons which may have had caused posterior capsule opacification in 3-piece
      silicone IOLs that had required Nd:YAG laser treatment. Special attention was
      given to 1) quality of cortical clean up, 2) type of haptic fixation, and 3)
      continuous curvilinear capsulorhexis (CCC) size and shape. MATERIALS AND METHODS:
      Human eyes obtained post-mortem implanted with 3-piece silicone optic - PMMA
      haptic (SI 40 NB) and 3-piece silicone optic - Prolene haptic (SI 30 NB) designs
      IOLs, accessioned between January 1993 and December 2000 were evaluated by gross
      examination from behind under an operating microscope using the Miyake-Apple
      posterior photographic technique. The area and intensity of Soemmerring's ring
      and type of fixation was studied in 457 eyes. The mean diameter of the CCC and
      relation of the CCC edge to the optic rim were analyzed in 221 eyes. RESULTS: 1)
      The amount of Soemmerring's ring formation was significantly larger in the group
      of IOLs requiring Nd:YAG capsulotomy in both the SI 40 NB and SI 30 NB design
      than in the IOLs without capsulotomies. 2) The percentage of not in-the-bag
      fixated IOLs in both the SI 40 NB and SI 30 NB design was larger in the "Nd:YAG
      groups", without being statistically significant. 3) The "Nd:YAG groups" showed a
      significant higher amount of non overlapping clock hours of the CCC edge in
      relation to the optic rim. CONCLUSION: 1) The data confirm the clinical
      assumption that the incidence of PCO is correlated with the cortical clean up. 2)
      Our findings also support the clinical assumption, that poor IOL fixation
      increases the risk of PCO. 3) This study also verifies the relation of the CCC to
      PCO, namely a relatively small CCC covering the entire optic rim is best to
      reduce the Nd:YAG laser rate.

PMID- 11573153
TI  - [Multilayer amniotic membrane transplantation for corneal ulcers not treatable by
      conventional therapy - a prospective study of the status of cornea and graft
      during follow-up].
AB  - PURPOSE: The purpose of this prospective clinical study was to evaluate the
      condition of the cornea (epithelium and vascularization) and the membrane
      presence and retraction during follow-up after amniotic membrane transplantation
      in patients with persistent corneal ulcers. PATIENTS AND METHODS: Between June
      1999 and November 2000 AM transplantation was performed in 30 consecutive
      patients (average age 59 +/- 17 years) with corneal ulcers refractory to clinical
      treatment. We evaluated the clinical diagnosis, localisation, size and depth of
      the ulcers, condition of the ocular surface and visual acuity before and after
      surgery. After complete removal of the epithelium and pannus, one (n=11), two
      (n=17) or three (n=2) layers of amniotic membrane were fixed with multiple
      interrupted sutures, depending on the depth of the lesion. A therapeutic contact
      lens was applied in most eyes and removed after one month. The most frequent
      diagnoses were chemical burn (5 x lime, 1 x lye and 1 x liquid aluminium), 7 x
      herpes, 3 x polyarthritis and 3 x blepharo-keratoconjunctivitis in neurodermitis.
      The ulcers had a medium length of 4.9 +/- 3.2 mm, a width of 3.5 +/- 3.0 mm and a
      depth ranging between 30 % and 95 % (68 +/- 21 %). RESULTS: Complete epithelial
      closure was achieved in 27 of 30 eyes (90 %). In 4 eyes a recurrent epithelial
      defect occurred after initial closure. At the 1-, 3- and 6 month follow-up the
      amniotic membrane was present in 93 %, 73 % or 30 %, respectively, but was more
      or less retractet in 52 %, 58 % or 67 %, respectively. A complete corneal
      epithelium was noted in 79 %, 89 % or 90 % of eyes, respectively. However,
      corneal neovascularization was observed in 24 %, 58 % or 60 % of eyes. Visual
      acuity was </= 20/400 in 60 % eyes preoperatively, but in 69 % after 3 months and
      in 78 % after 6 months of follow-up. CONCLUSION: In persistent corneal ulcers,
      amniotic membrane transplantation should be considered in early stages to achieve
      permanent epithelial closure in a less inflamed eye thus avoiding penetrating
      keratoplasty a chaud or conjunctival flaps. However, in eyes with broad
      descemetocele especially following chemical burns, this treatment modality does
      not seem to be effective.

PMID- 11573154
TI  - [Combined phacoemulsification and goniotrephination in primary open-angle
      glaucoma and pseudoexfoliation glaucoma - a retrospective analysis].
AB  - BACKGROUND: During the last few years combined cataract and glaucoma surgery is
      an established method to control intraocular pressure (IOP) and visual
      rehabilitation in patients with cataract and glaucoma. Despite this, there are
      currently only few data concerning the results of combined surgery for primary
      open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG). PATIENTS AND
      METHODS: To study the course of PEXG and POAG with respect to IOP regulation and
      visual acuity, 100 eyes with POAG (72 patients) and 22 with PEXG (19 patients)
      were evaluated which underwent a combined phacoemulsification and
      goniotrephination between 1993 and 1997. All patients had no glaucoma or other
      ocular surgery before. The mean follow up after operation was 39.5 (range 16 -
      72) months. RESULTS: The mean preoperative IOP in PEXG (31.8 +/- 10.3 mm Hg) was
      significantly higher than in the POAG group (25.3 +/- 6.4 mm Hg) (p=0.0004). At
      follow up IOP decreased to 16.7 +/- 2.8 mm Hg (POAG) and 15.1 +/- 4.0 mm Hg
      (PEXG) (p < 0.0001). The absolute IOP lowering effect was significantly better
      for PEXG than for POAG (p=0.0003). All patients received medical treatment before
      surgery, whereas at follow up 59.0 % (POAG) and 81.8 % (PEXG) were untreated. The
      median preoperative visual acuity for the POAG was 0.32 (PEXG 0.25), visual
      outcome 0,63 (PEXG 0.5). CONCLUSION: The combined cataract and glaucoma surgery
      is a successful method of IOP control and visual rehabilitation. It seems that
      there is a tendency for a better efficiency and an untreated IOP regulation after
      surgery for PEXG. Thereby early surgical intervention could be an advantage for
      this glaucoma entity.

PMID- 11573155
TI  - [Long-term results of large diameter keratoplasties in the treatment of severe
      chemical and thermal eye burns].
AB  - BACKGROUND: In severe chemical and thermal eye burns the limbal stem cells, which
      are important for the regeneration of the corneal epithelium, are lost. In our
      retrospective study two questions were investigated: 1) is it possible to restore
      the limbal region by transplantation of large diameter keratoplasties 2) has the
      time of transplantation an influence on the clinical outcome. PATIENTS AND
      METHOD: In a retrospective study the outcome of 48 eyes (43 patients) with severe
      chemical and thermal burns were analysed. Large diameter (11 - 12 mm) penetrating
      keratoplasties were performed between 1987 and 1996. Complete limbal deficiency
      was present in 17 eyes, while 31 eyes had developed sterile corneal ulceration.
      According to the time of transplantation three different groups were
      distinguished. Group I (early keratoplasty, n=24): transplantation within 3
      months after the accident (mean: 26 days). Group II (intermediate keratoplasty,
      n=13): transplantation between 4 - 18 months after the burn (mean: 190 days).
      Group III (late keratoplasty, n=11): surgery more than 18 months after the injury
      (mean: 36.6 months). RESULTS: Follow-up time was 28.4 months in early
      keratoplasty, 26.4 months after intermediate keratoplasty, and 34.3 months in
      late keratoplasty. Long-term results of the keratoplasties were poor. 60.4 % of
      the transplants failed due to surface problems, 18.8 % due to endothelial
      rejection episodes. Late keratoplasties were significantly more successful than
      intermediate keratoplasties. 25 % of the early keratoplasties and 36.4 % of the
      late keratoplasties showed an intact limbal region at the end of the follow-up
      time, but none of intermediate keratoplasties. CONCLUSION: The prognosis for
      large diameter keratoplasties depends on the time of transplantation. Late and
      early keratoplasties had the best results. However, survival of heterologous stem
      cells is limited.

PMID- 11573156
TI  - [Clinical predictors of retinal detachment after open globe injury].
AB  - BACKGROUND: A retinal detachment after open globe injury has important prognostic
      and therapeutic implications. MATERIAL AND METHODS: To determine whether retinal
      detachment following open globe injury could be predicted by clinical factors, we
      retrospectively evaluated 52 patients (52 eyes) with open globe injury admitted
      to our department. The Birmingham Eye Trauma Terminology System was used. Only
      patients which open eye injuries were evaluated. The results were registered
      during the 7 days after the accident. RESULTS: In the week after the open globe
      injury, retinal detachment was present in 40.3 %. 100 % of the patients with
      previous cataract operation (with IOL) developed a retinal detachment (p < 0.01).
      Retinal detachment also correlated significantly with visual acuity less than
      hand movement and retained intraocular foreign bodies. 19 (95 %) of the 20
      patients with a visual acuity less than hand movement had retinal detachment
      versus only 2 (9 %) patients with visual acuity of hand movement or better (p <
      0.01). 6 (66.6 %) of the 9 patients with intraocular foreign bodies had retinal
      detachment compared to 15 (34.8 %) of the 46 patients without intraocular foreign
      bodies (p=0.01). Logistic regression analysis confirmed this variables as
      independent predictors of retinal detachment. CONCLUSION: We conclude that
      previous cataract operation, versus less than hand movement and the presence of
      intraocular foreign bodies are predictive to retinal detachment.

PMID- 11573157
TI  - [Investigations on the cornea donation at the Martin-Luther-University Halle
      Wittenberg].
AB  - AIM: We analysed the number of the potential cornea donors of the Martin-Luther
      University, Halle-Wittenberg over a four-years period, 1995 to 1998 in
      relationships to the number of the actual donors. PATIENTS AND METHODS: We
      retrospectively reviewed the data of 2545 patients who died at the hospitals of
      the Martin-Luther-University, Halle-Wittenberg over a four-years period, from
      January 1995 to December 1998. The medical records of the patients were inspected
      and contraindications for cornea donation examined. The patients who were younger
      than 12 months were omitted in our analysis. The patients with at least one
      contraindication were excluded as potential cornea donors. Additionally we
      registered the actual cornea donors of the hospitals of the Martin-Luther
      University, Halle-Wittenberg between 1995 to 1998. RESULTS: The mean age of the
      died patients was 60 years. Because of contraindications 597 patients (23.5 %)
      were excluded from the cornea donation. An acute sepsis with 25.1 % as well as
      leukemias and lymphomas with 24.8 % matched about half of the exclusion criteria.
      In the period of investigation we counted 1948 potential cornea donors. In the
      hospitals of the Martin-Luther-University, Halle-Wittenberg only 57 (2.9 % of
      potential donors) actual cornea donors have been registered. CONCLUSIONS: The
      possible leading causes for the large discrepancy between the number of the
      potential and actual donors are: (1) the imperfect identification of potential
      donors, (2) the donor family have not been asked and (3) the denial of consent by
      the potential donors family.

PMID- 11573158
TI  - [Corneoretinal dystrophy (Bietti)-- Long-term course of one patient over a period
      of 30 years, and interindividual variability of clinical and electrophysiological
      findings in two patients].
AB  - BACKGROUND: A tapetoretinal dystrophy with crystalline deposits of the retina and
      limbal cornea was described by Bietti in 1937. To date, only a few cases with
      long-term follow up have been reported. PATIENTS AND METHODS: Two patients are
      presented including the clinical findings, fluorescein angiography,
      electrophysiology [electroretinography (ERG); electrooculography (EOG),
      multifocal electroretinography (MERG)], adaptometry, and transmission electron
      microscopy (TEM) of peripheral blood lymphocytes. The clinical findings were at
      least in part documented over a period of 30 years. RESULTS: The most striking
      features were deposits in the retina and cornea associated with crystalloid
      lysosomal inclusions in peripheral lymphocytes, and choroidal atrophy especially
      in advanced stages of the disease. The light rise (EOG), rod- and cone-driven
      responses (ERG), the responses of the MERG and visual fields were affected
      progressively during the course. These advanced changes of the retinal pigment
      epithelium and choriocapillaris were observed in the 2(nd) decade already.
      CONCLUSIONS: The findings of deposits in the cornea, retina and lymphocytes may
      help to differentiate BCD from other chorioretinal dystrophies. The results
      confirm a variable course in clinical expression of BCD between individuals.

PMID- 11573159
TI  - [Painless acanthamoeba keratitis].
AB  - BACKGROUND: Acanthamoeba keratitis is a severe, painful corneal infection found
      in contact lens wearers. The entity can easily be confused with herpetic or
      fungal keratitis, especially if no ocular pain is reported. HISTORY AND SIGNS: A
      32-year old myopic female presented a unilateral keratitis of unknown etiology
      since 3 weeks. Administration of topical antiviral substances and corticosteroids
      led only to temporary improvement of the condition. The patient complained of
      photophobia but not of ocular pain. The affected eye showed corneal edema,
      central stromal thickening, descemet's striae as well as fibrin deposits on the
      corneal endothelium and in the anterior chamber. DIAGNOSIS: An aqueous specimen
      was negative for a viral infection. A culture for bacteria was negative.
      Staphylococci were cultured from corneal scrapings and Enterococci from the
      contact lens solution. Another corneal scraping revealed Acanthamoeba class II (6
      weeks after the onset of symptoms). CLINICAL COURSE: Under treatment with
      propamidine, polymyxin b, neomycin, gramicidin and polyhexidine (topical) as well
      as fluconazole/ketoconazole (systemic) the diameter of the annular infiltrate,
      which had developed decreased, but the infiltrate persisted. In the further
      course, the infiltrate persisted while the amount of fibrin in the anterior
      chamber increased. Penetrating keratoplasty was performed. Histologic examination
      of the host corneal tissue revealed massive infiltration with Acanthamoeba.
      CONCLUSIONS: Severe pain and history of wearing contact lenses are features
      suggestive of Acanthamoeba keratitis. The patient presented here had a history of
      contact lens wear, but no ocular pain was reported. The characteristic annular
      infiltrate had a late onset. Bacterial superinfection could not be ruled out.
      Therapeutic penetrating keratoplasty had to be performed as the condition
      deteriorated inspite of intensive chemotherapy. With penetrating keratoplasty a
      good visual acuity could be regained.

PMID- 11573160
TI  - [Secondary ocular syphilis with chorioretinitis of the posterior pole - a case
      report].
AB  - BACKGROUND: Diagnosis of syphilis is often very difficult due to the absence of
      typical organ manifestation. In addition syphilis has the ability to imitate any
      ocular inflammation. This may result in misdiagnosis and delay of appropriate
      antimicrobial therapy. Up to now the first choice therapy is penicillin. CASE
      REPORT: We report about an otherwise healthy, 40 year-old-woman, who was referred
      to the Department of Ophthalmology, University of Tuebingen, due to an unclear
      loss of visual acuity (OD 0.1 and OS 0.4). The fundus examination disclosed focal
      chorioretinitis on the posterior pole, which was verified in fluorescein
      angiography. Secondary syphilis was diagnosed due to positive serological
      testing. Medical treatment consisted in Penicillin (i.m.) for 2 weeks and
      additional oral corticosteroids, which were tapered down slowly. After 3 months
      visual acuity had improved to 0.9 in the right and to 1.0 in the left eye. The
      former chorioretinitis regions showed only hyperpigmentation. CONCLUSIONS:
      Laboratory syphilitic testing should be performed in every uveitis.

PMID- 11573161
TI  - [Conjunctival cyst: subconjunctival luxation of the lens following ocular
      contusion - a case report].
AB  - PATIENT: Presentation of a 75-year-old female with subconjunctival lens luxation,
      that was initially misdiagnosed as conjunctival cyst. Initial examination had
      been difficult due to vascularized stromal corneal scars and a large hyphema. The
      ocular history revealed an ocular contusion 11 months ago. Aphakia with
      subconjunctival lens luxation, iris incarceration, iridodialysis and covered
      scleral rupture were diagnosed by inspection, palpation, slit-lamp biomicroscopy,
      gonioscopy and ultrasound biomicroscopy. The lens and incarcerated iris tissue
      were removed, the scleral wound was sutured and a penetrating keratoplasty was
      performed in combination with anterior vitrectomy and implantation of a
      transclerally sutured posterior chamber lens. The histologic investigation of the
      subconjunctival tissue showed the complete lens with intact lens capsule and
      surrounding subconjunctival connective tissue. CONCLUSION: Hyphemas following
      ocular contusion are frequent findings. A large hyphema may masquerade
      alterations of other ocular structures. The differential diagnosis of
      posttraumatic prominent conjunctival "tumors" should include subconjunctival
      luxation of the lens.

PMID- 11573162
TI  - [Laudatio Prof. Dr. J. Reiner].

PMID- 11573163
TI  - The Y chromosome pool of Jews as part of the genetic landscape of the Middle
      East.
AB  - A sample of 526 Y chromosomes representing six Middle Eastern populations
      (Ashkenazi, Sephardic, and Kurdish Jews from Israel; Muslim Kurds; Muslim Arabs
      from Israel and the Palestinian Authority Area; and Bedouin from the Negev) was
      analyzed for 13 binary polymorphisms and six microsatellite loci. The
      investigation of the genetic relationship among three Jewish communities revealed
      that Kurdish and Sephardic Jews were indistinguishable from one another, whereas
      both differed slightly, yet significantly, from Ashkenazi Jews. The differences
      among Ashkenazim may be a result of low-level gene flow from European populations
      and/or genetic drift during isolation. Admixture between Kurdish Jews and their
      former Muslim host population in Kurdistan appeared to be negligible. In
      comparison with data available from other relevant populations in the region,
      Jews were found to be more closely related to groups in the north of the Fertile
      Crescent (Kurds, Turks, and Armenians) than to their Arab neighbors. The two
      haplogroups Eu 9 and Eu 10 constitute a major part of the Y chromosome pool in
      the analyzed sample. Our data suggest that Eu 9 originated in the northern part,
      and Eu 10 in the southern part of the Fertile Crescent. Genetic dating yielded
      estimates of the expansion of both haplogroups that cover the Neolithic period in
      the region. Palestinian Arabs and Bedouin differed from the other Middle Eastern
      populations studied here, mainly in specific high-frequency Eu 10 haplotypes not
      found in the non-Arab groups. These chromosomes might have been introduced
      through migrations from the Arabian Peninsula during the last two millennia. The
      present study contributes to the elucidation of the complex demographic history
      that shaped the present-day genetic landscape in the region.

PMID- 11573164
TI  - Establishing the scope of dentistry.

PMID- 11573165
TI  - Incidence of complications and problems related to orthognathic surgery: a review
      of 655 patients.
AB  - PURPOSE: This retrospective report evaluates the incidence of pre-, intra-, and
      postoperative complications of orthognathic surgery and their significance to the
      patient. PATIENTS AND METHODS: The clinical records and radiographs of 655
      patients operated on in Vaasa Central Hospital, Finland during a 13-year period
      between 1983 and 1996 were examined. The total number of operations was 689. All
      notes referring to problems or complications from the orthodontic phase to the
      varying postoperative follow-up times were gathered and analyzed. RESULTS: The
      most common complication was a neurosensory deficit in the region innervated by
      the inferior alveolar nerve; mild in 32% of patients (183 of 574 patients with an
      osteotomy in the mandible) and disturbing in 3% of patients (18/574). The most
      serious complication was severe intraoperative bleeding in 1 patient
      necessitating major blood transfusions and later embolization of the internal
      maxillary artery. There were no fatal complications. The incidence of other
      problems was low, and there were very few patient complaints. CONCLUSIONS:
      Despite the great variety of severe complications reported in the literature,
      their frequency seems to be extremely low, and orthognathic surgery treatment can
      be considered to be a safe procedure.

PMID- 11573167
TI  - Use of intraoperative cytologic assessment of mandibular marrow scrapings to
      predict resection margin status in patients with squamous cell carcinoma.
AB  - PURPOSE: This study assessed the feasibility of intraoperative microscopic
      assessment of mandibular bone resection margins in patients undergoing segmental
      resection of mandible for treatment of squamous cell carcinoma. PATIENTS AND
      METHODS: This prospective pilot study involved 7 consecutive patients undergoing
      segmental resection of mandible as part of surgical treatment of oral squamous
      cell carcinoma. Cytologic examination of smear/touch preparations of 35 bone
      marrow scrapings, including simulated positive margins, was performed. RESULTS:
      "Malignant" excision margins produced a high cell yield, and it was easy to
      assign samples to malignant or benign categories on microscopic examination. All
      the simulated positive margins were easily identified. No false positive results
      were found. CONCLUSION: Cytologic examination of bone excision margin scrapings
      is a rapid, inexpensive, and accurate technique. This study confirms its
      feasibility and accuracy in cases of mandibular resection for squamous cell
      carcinoma.

PMID- 11573168
TI  - Reconstruction of intraoral defects after cancer surgery using cervical pedicle
      flaps.
AB  - PURPOSE: This article reports the results of using cervical myocutaneous flaps
      for reconstruction of small- and medium-sized oral defects. PATIENTS AND METHODS:
      One hundred thirty-one cervical pedicle flaps were used for reconstruction of the
      defects after resection of oral cancer. Primary sites of the lesions were the
      tongue, buccal mucosa, floor of the mouth, and lower gingiva. RESULTS: Infrahyoid
      myocutaneous flaps were used in 53 cases, sternocleidomastoid flaps in 47 cases,
      and platysma flaps in 31 cases. Among the 131 patients, there was complete
      necrosis of the skin paddle in 5 cases and partial necrosis in 7 cases. The
      success rate was 92.5%, 89.4%, and 90.3%, respectively for the 3 types of flaps.
      CONCLUSIONS: It was concluded that cervical pedicle flaps have clinical value in
      selected patients needing reconstruction of small- and medium-sized defects after
      intraoral cancer surgery.

PMID- 11573169
TI  - The partial-thickness cross-lip flap for correction of postoncologic surgical
      defects.
AB  - PURPOSE: Abbe and Estlander cross-lip flaps have been described and designed as a
      full-thickness flap to reconstruct a full-thickness excisional defect. Some Mohs
      surgical excisions and other serial excisions leave partial-thickness defects.
      This article reviews a series of partial-thickness cross-lip flaps, which
      included some orbicularis oris muscle in the vermilion region but otherwise was a
      subcutaneous flap. PATIENTS AND METHODS: In the last 7 years, 110 patients with
      lip cancer had their postsurgical defects reconstructed 24 to 72 hours after the
      resection. In all cases, negative margins were established by histologic
      evaluation or Mohs micrographic surgery. Twenty of 29 patients had Abbe- and
      Estlander- (lip-switch) type flaps, which were composed of a musculomucosal
      pedicle of 1.25 to 1.50 cm and an attached skin/subcutaneous flap trimmed to fit
      the defect. The remainder had full-thickness lip-switch flaps. RESULTS: There
      were no vascular complications in either group. Four patients had notching or
      trapdoor- type bulking, which were revised after 3 to 6 months. CONCLUSION: The
      partial-thickness cross-lip flap has the same viability as the full-thickness
      flap within 1 cm from the inferior border of the mandible.

PMID- 11573170
TI  - The use of arthrocentesis for the treatment of osteoarthritic temporomandibular
      joints.
AB  - PURPOSE: The purpose of this retrospective study was to determine the efficacy of
      arthrocentesis in restoring the functional capacity of osteoarthritic
      temporomandibular joints (TMJ). PATIENTS AND METHODS: This study involved 36
      patients (29 females, 7 males; age range, 16 to 54 years, mean, 37.36 +/- 14.60
      years) presenting with 38 dysfunctional joints that had not responded to
      conservative treatment. The postarthrocentesis status (follow-up period 6 to 62
      months, mean 20.7 +/- 20.5 months) of the TMJs was determined by patient self
      evaluation using visual analog scales and clinical examination. RESULTS: Of the
      38 TMJs treated with arthrocentesis, 26 joints reacted favorably to the
      treatment; pain and dysfunction scores were reduced from 9.86 +/- 0.73 to 3.39 +/
      0.76 and from 11.34 +/- 0.66 to 3.4 +/- 0.69, respectively (P <.001). Self
      assessed general improvement/deterioration was +4.90 +/- 2.10 (on a scale of -7
      to +7). Maximal mouth opening increased from 24.40 +/- 2.70 mm to 43.20 +/- 3.10
      mm (P <.001). Lateral and protrusive jaw movements also increased in magnitude.
      In 14 patients in whom no improvement was noted, arthrocentesis acted as a
      diagnostic tool before surgical treatment. CONCLUSIONS: Arthrocentesis is a safe
      and rapid procedure that in many instances results in the osteoarthritic TMJs
      returning to a healthy functional state. Failure of arthrocentesis suggests that
      the painful limitation is most probably caused by changes such as fibrous
      adhesions or osteophytes that require surgical intervention for their removal.

PMID- 11573172
TI  - A comparative evaluation of osteosynthesis with lag screws, miniplates, or
      Kirschner wires for mandibular condylar process fractures.
AB  - PURPOSE: This study compared the clinical and radiologic outcomes of open
      treatment of mandibular condylar process fractures using lag screws, miniplates,
      or Kirschner wires. PATIENTS AND METHODS: Open reduction and internal fixation
      was performed for severely displaced or dislocated mandibular condylar process
      fractures in 23 patients (26 fractures) using Eckelt lag screws, in 10 patients
      (10 fractures) using Kirschner wires, and in 21 patients (22 fractures) using
      miniplates. Clinical and radiologic evaluations were made 6 months
      postoperatively and at final follow-up (mean, 18.4 months; range, 7 to 106
      months). Radiologic evaluation included accuracy of reduction of the fractured
      condylar processes and changes in ramus height. RESULTS: Most fractured condylar
      processes (approximately 90%) were repositioned precisely in all groups. A
      shortening of the ramus of more than 5 mm was observed significantly more
      frequently (P <.05) in the miniplate group than in the lag screw group at 6
      months. The condyles were severely resorbed in 2 or 3 patients in each group. All
      of these patients were associated with malunion, and partial bone resorption of
      the condyles was seen during the first 6 months. The relation between reduction
      or screw position and bone healing in patients treated with lag screws indicated
      that correct reduction and screw insertion allowed normal bone healing. The
      patients in all groups showed satisfactory clinical results. No significant
      intergroup differences were noted in maximum mouth opening and laterotrusion.
      However, deviation during mouth opening was significantly greater (P <.05) in
      cases treated with miniplates than with lag screws. CONCLUSION: Lag screw
      osteosynthesis may be more advantageous for restoration of ramus height than
      miniplates or Kirschner wires.

PMID- 11573174
TI  - The subcranial approach for the treatment of cerebrospinal fluid rhinorrhea: a
      report of 10 cases.
AB  - PURPOSE: Because of the likelihood of meningitis and other intracranial
      complications, optimal treatment for a cerebrospinal fluid (CSF) fistula is to
      close the leak. The neurosurgical approach to the management of CSF rhinorrhea
      has been by intracranial access. Extracranial approaches are now gaining
      acceptance as the preferred method for initial treatment of CSF leakage, because
      the success rates are reasonable, and the morbidity is lower. This report
      describes the results of using such an approach. PATIENTS AND METHODS: The
      extended subcranial approach was used in 10 patients with CSF rhinorrhea.
      Selection criteria included defects of the anterior skull base greater than 15 mm
      in diameter, defects not accessible by endoscopes, fistula sites that could not
      be localized preoperatively, and multiple and transverse fractures of the
      cribriform region. Follow-up ranged from 8 to 23 months, with a mean of 17
      months. RESULTS: Resolution of rhinorrhea was achieved in 9 (90%) of the
      patients. Anosmia was the only postoperative complication, occurring in 8
      patients. CONCLUSION: The authors conclude that the extended subcranial approach
      to the anterior skull base is a safe, versatile, and effective procedure for the
      surgical treatment of CSF rhinorrhea involving the anterior skull base.

PMID- 11573175
TI  - Peripheral glycerol injections in the treatment of idiopathic trigeminal
      neuralgia: retrospective analysis of 157 cases.
AB  - PURPOSE: This study presents the results of peripheral glycerol injections in
      patients with idiopathic trigeminal neuralgia. PATIENTS AND METHODS: The patients
      who either failed to respond to drug therapy or developed serious side effects
      were treated by means of glycerol injections. Medical records and questionnaires
      on 157 patients treated between 1983 and 1996 were evaluated. The minimum follow
      up period for each patient was 4 years. RESULTS: The study population included 65
      males and 92 females. The right side (112 patients, 71%) was affected more
      commonly than the left. The most common distribution was in the second and the
      third trigeminal divisions. The initial success rate was 98%. Pain recurred in 60
      patients and was most frequently recorded between 25 and 36 months postinjection
      (28 of the 60 recurrences). These patients were successfully reinjected. At the
      end of 4 years, complete or almost complete pain relief was obtained in 154
      patients. CONCLUSIONS: Peripheral glycerol injection is a minimally invasive and
      useful technique to manage trigeminal neuralgia, with a high success rate and low
      incidence of morbidity.

PMID- 11573177
TI  - Obstructive sleep apnea surgery: genioglossus advancement revisited.
AB  - PURPOSE: This study evaluated the accuracy of a genioglossus advancement (GA)
      technique (rectangular window) to incorporate the genial tubercle/genioglossus
      muscle complex (GGC) in patients with obstructive sleep apnea. METHODS: This
      prospective study consisted of 38 consecutive patients who underwent GA.
      Preoperative localization of the GGC was based on the cephalometric and panoramic
      radiographs, as well as digital palpation in the floor of mouth. Immediately
      after completion of the osteotomy, the presence of the genial tubercles and the
      amount of the genioglossus muscle captured in the bone flap were examined
      directly. RESULTS: All 38 pairs of genial tubercles were captured. Thirty-one
      patients had both bellies of the genioglossus muscle incorporated. Two patients
      had a complete belly and a partial (>50%) belly of the muscle captured. Five
      patients had only a portion (>50%) of both muscle bellies included. The
      incomplete incorporation of the muscles in the bone flap was caused by the
      limited lateral extension of the osteotomy beyond the genial tubercles. The
      causes of the limited lateral osteotomy extension included crowding of the lower
      incisors as well as the presence of elongated and/or medially angulated canine
      roots. CONCLUSION: The results of this study show that the rectangular osteotomy
      technique accurately captures the genial tubercles and enables an adequate amount
      of the genioglossus muscle to be incorporated and advanced. However, limited
      lateral extension of the osteotomy can result in a decreased incorporation of
      genioglossus muscle in some patients.

PMID- 11573179
TI  - Histochemical study of the elastic fibers in pathologic human temporomandibular
      joint discs.
AB  - PURPOSE: This study investigated histochemically the elastic fibers in human
      temporomandibular joint (TMJ) discs with varying degrees of tissue
      degeneration/regeneration to determine whether there are differences that
      correlate with the histologic findings. MATERIALS AND METHODS: Ten diseased human
      TMJ discs and 2 control specimens were studied histochemically by staining with
      Weigert's resorcin-fuchsin after oxidation with peracetic acid. This technique
      selectively stains elastic, elaunin, (pre-elastic), and oxytalan fibers. RESULTS:
      In TMJ discs with an abnormal collagen fiber arrangement, an increased number of
      oxytalan fibers could be observed, contrary to discs with scar-like tissue
      transformation in which oxytalan fibers were decreased in number. In discs
      showing tears and clefts, the oxytalan fibers run perpendicular to the defects,
      whereas elaunin and elastic fibers were mainly circumferentially arranged. In
      discs with chondroid metaplasia, elastic, elaunin, and oxytalan fibers were
      extensively detected. CONCLUSIONS: It is hypothesized that the elastic, elaunin,
      and oxytalan fibers found in severely damaged discs appear to ensure
      biomechanical compliance by reinforcing regions devoid of collagen bundles and
      thus function as shock absorbers of stretch and compression.

PMID- 11573181
TI  - Measurement of the maxilla and zygoma as an aid in installing zygomatic implants.
AB  - PURPOSE: This study used maxillary and zygomatic measurements to obtain
      information for installing zygomatic implants. PATIENTS AND METHODS: Angular and
      linear distances between the maxilla and the zygoma were measured in 12 cadavers
      (n = 22 sides) classified into short and tall groups by height (140 to 159 cm and
      160 to 180 cm, respectively). RESULTS: Based on mean and standard deviation
      values, the installation angle of zygomatic implants was between 43.8 degrees and
      50.6 degrees. The distance between the crest of the maxillary alveolar process
      near the palate and the jugale (Ju) point of the zygoma was between 44.3 and 54.3
      mm. The minimum distance between the most lateral corner of the maxillary sinus
      and the Ju point was 6.41 mm, and the minimum anteroposterior length of the
      zygoma was 5.68 mm in the shorter group. CONCLUSIONS: When the installation angle
      of zygomatic implants is 43.8 degrees or less, perforation of the maxilla and the
      zygoma or the infratemporal fossa must be avoided. When the angle is 50.6 degrees
      or more, perforation of the orbital floor must be avoided. Special attention is
      needed to ensure osseointegration in shorter patients, because the distance
      between the most lateral corner of the antrum supporting the zygomatic implant
      and the Ju point is 10 mm or less. The apex of the implant is 3.75 mm in
      diameter, and the thickness of the zygoma must be 5.75 mm or more. The threads of
      the implant must not be exposed from the zygoma in shorter patients.

PMID- 11573182
TI  - A biomechanical evaluation of mandibular angle fracture plating techniques.
AB  - PURPOSE: The purpose of this investigation was evaluate the biomechanical
      behavior of a vast array of fixation philosophies and techniques that address
      mandibular angle fractures. MATERIALS AND METHODS: A total of 150 polyurethane
      synthetic mandible replicas (Synbone, Laudquart, Switzerland,) were used in this
      investigation. Five controls and 5 each of 14 different fixation philosophies and
      techniques were subjected to vertical loading at the incisal edge and then
      repeated for contralateral loading in the molar region by an Instron 1331
      (Instron, Canton, MA) servohydraulic mechanical testing unit. The fixation
      philosophies and techniques evaluated were the lag screw technique, monocortical
      superior border plating techniques with varying sizes of plates and screws,
      monocortical 2-plate techniques with varying forms of fixation, monocortical
      tension band systems with associated bicortical stabilization plates of various
      types, and various forms of reconstruction plates. Load/displacement data within
      a 0 to 200 N range were recorded. Yield load, yield displacement, and stiffness
      were determined. Mean and standard deviations were calculated, and statistically
      significant differences within and among categories were determined using an
      analysis of variance (P <.05). Second-order polynomial best-fit curves were also
      created for each group to further evaluate and compare the mechanical behavior.
      RESULTS: For incisal edge loading, statistically significant differences (P <.05)
      were found for stiffness between some of the monocortical superior border
      fixation techniques, as well as for yield displacement between several forms of
      monocortical 2-plate fixation techniques. No other differences were found within
      categories or among the groups that best represented their categories. For
      contralateral molar loading, statistically significant differences existed within
      and among categories. CONCLUSIONS: Under the conditions of this experiment, all
      systems met or exceeded currently identified postoperative functional
      requirements for incisal edge loading, but failed to meet them for contralateral
      molar loading.

PMID- 11573183
TI  - Radiopaque mass at the mandibular ramus.

PMID- 11573184
TI  - Grade inflation or typographical error: the accuracy of residency applicants'
      information.

PMID- 11573185
TI  - Calcium pyrophosphate dihydrate crystal deposition disease in the
      temporomandibular joint: diagnostic difficulties and clonal chromosome
      aberrations in a case followed up for 5 years.

PMID- 11573186
TI  - Impacted knife injuries in the maxillofacial region: report of 2 cases.

PMID- 11573187
TI  - Bilateral gingival metastasis of lung adenocarcinoma: report of a case.

PMID- 11573188
TI  - Odontogenic myxoma showing active epithelial islands with microcystic features.

PMID- 11573189
TI  - Cavernous hemangioma of the temporalis muscle: report of a case.

PMID- 11573190
TI  - Use of upper-lid blepharoplasty full-thickness skin for peri-implant keratinized
      tissue grafting: a report of 2 cases.

PMID- 11573191
TI  - Carcinoma in an inverted papilloma of the pterygopalatine fossa: report of a
      case.

PMID- 11573192
TI  - Cytokine levels and the effect of prednisolone on Kimura's disease: report of a
      case.

PMID- 11573193
TI  - Modified uvulopalatopharyngoplasty: the lateral inversion flap technique.

PMID- 11573194
TI  - A simplified technique of genioplasty with simultaneous widening or narrowing of
      the chin.

PMID- 11573195
TI  - Faces in the dust.

PMID- 11573196
TI  - Apopletic or apocolyptic?

PMID- 11573197
TI  - Different views of managed care.

PMID- 11573198
TI  - Different views of managed care.

PMID- 11573199
TI  - Fibronectin, integrins, and growth control.
AB  - Cell proliferation is controlled not only by soluble mitogens but also by
      components of the extracellular matrix (ECM) such as fibronectin, to which cells
      adhere via the integrin family of transmembrane receptors. Input from both growth
      factor receptors and integrins is required to stimulate progression through the
      G1 phase of the cell cycle, via induction of G1 cyclins and suppression of
      inhibitors of the G1 cyclin-dependent kinases. Extensive crosstalk takes place
      between integrin and growth factor receptor signaling pathways, and mitogenic
      signaling is weak and transient in the absence of integrin-mediated cell
      adhesion. In normal untransformed cells, all of the important mitogenic signal
      transduction cascades, namely those downstream of the Ras and Rho family small
      GTPases and the phosphoinositide 3-OH kinase-PKB/Akt pathway, are regulated by
      integrin-mediated cell adhesion. As a result, these cells are anchorage-dependent
      for growth. In contrast, constitutive activity of each of these pathways has been
      reported in cancer cells, which not only reduces their mitogen dependence but
      also allows these cells to grow in an anchorage-independent fashion.

PMID- 11573200
TI  - Rapamycin-sensitive phase of 3T3-L1 preadipocyte differentiation after clonal
      expansion.
AB  - Inhibition of insulin-induced 3T3-L1 preadipocyte differentiation by rapamycin
      has been attributed to a blockade of the early critical clonal expansion phase of
      the adipogenic program. Rapamycin binds to, and inhibits, mTOR (mammalian target
      of rapamycin), leading to diminution of p70 S6 kinase activity and eukaryotic
      initiation factor 4E binding protein 1 (eIF4E-BP1) function. Our objective was to
      determine if rapamycin-sensitive pathways exist subsequent to the clonal
      expansion phase. We determined that the mitotic clonal expansion was complete by
      day 4 of the differentiation protocol, based on the response to Ara-C (cytosine
      beta-D-arabinofuranoside), which only inhibits differentiation when administered
      during this phase. Treatment of differentiating 3T3-L1 cells with rapamycin,
      starting on day 4, exerted potent negative effects on glycerol phosphate
      dehydrogenase activity, and triacylglycerol accumulation, as well as on the
      protein expression of adipogenic transcription factors, C/EBPalpha and PPARgamma.
      Insulin-stimulated p70 S6 kinase activity, and its inhibition by rapamycin, were
      comparable in preadipocytes at day 0 vs. day 4 post-differentiation. We conclude
      that a component of the adipogenic program, operating after the completion of
      clonal expansion, is inhibited by rapamycin, suggesting an ongoing need for mTOR
      function in this process.

PMID- 11573201
TI  - Plasminogen activator inhibitor-1 regulates cell adhesion by binding to the
      somatomedin B domain of vitronectin.
AB  - Plasminogen activator inhibitor-1 (PAI-1) binds to the somatomedin B (SMB) domain
      of vitronectin. It inhibits the adhesion of U937 cells to vitronectin by
      competing with the urokinase receptor (uPAR; CD87) on these cells for binding to
      the same domain. Although the inhibitor also blocks integrin-mediated cell
      adhesion, the molecular basis of this effect is unclear. In this study, the
      effect of the inhibitor on the adhesion of a variety of cells (e.g., U937, MCF7,
      HT-1080, and HeLa) to vitronectin was assessed, and the importance of the SMB
      domain in these interactions was determined. Although PAI-1 blocked the adhesion
      of all of these cells to vitronectin-coated wells, it did not block adhesion to a
      variant of vitronectin which lacked the SMB domain. Interestingly, HT-1080 and
      U937 cells attached avidly to microtiter wells coated with purified recombinant
      SMB (which does not contain the RGD sequence), and this adhesion was again
      blocked by the inhibitor. These results affirm that PAI-1 can inhibit both uPAR-
      and integrin-mediated cell adhesion, and demonstrate that the SMB domain of
      vitronectin is required for these effects. They also show that multiple cell
      types can employ uPAR as an adhesion receptor. The use of purified recombinant
      SMB should help to further define this novel adhesive pathway, and to delineate
      its relationship with integrin-mediated adhesive events.

PMID- 11573202
TI  - pRb2/p130 and p107 control cell growth by multiple strategies and in association
      with different compartments within the nucleus.
AB  - It has been recently reported that retinoblastoma family proteins suppress cell
      growth by regulating not only E2F-dependent mRNA transcription but also rRNA and
      tRNA transcription and, through HDAC1 recruitment, chromatin packaging. In the
      present study we report data showing that these various control strategies are
      correlated, at least in part, with nuclear compartmentalization of retinoblastoma
      proteins. In a first series of experiments, we showed that pRb2/p130 and p107 are
      not evenly distributed within the nucleus and that cell cycle-dependent binding
      with E2F4 changes also as a function of their subnuclear localization. Namely, in
      the nucleoplasm pRb2/p130-E2F4 complexes are more numerous during G0/G1 while in
      the nucleolus they increase in S phase. Partially different functions for p107
      are suggested since p107-E2F4 complexes in the nucleoplasm are more numerous is S
      phase with respect to G0/G1 and no cell cycle change is observed in the
      nucleolus. In a second series of experiments we showed that pRb2/p130, p107,
      E2F4, and pRb2/p130-HDAC1 complexes are all inner nuclear matrix-associated
      proteins and localize to sites different from pRb/p105 ones. We provide further
      evidence of multiple and partially distinct retinoblastoma protein family
      functional roles during cell cycle. Moreover, our data support emerging evidence
      for functional interrelationships between nuclear structure and gene expression.

PMID- 11573203
TI  - Detection of murine adult bone marrow stroma-initiating cells in Lin(-)c-fms(+)c
      kit(low)VCAM-1(+) cells.
AB  - We attempted to characterize the phenotype of cells which initiate fibroblastic
      stromal cell formation (stroma-initiating cells: SICs), precursor cells for
      fibroblastic stromal cells, based on the expression of cell surface antigens.
      First, we stained adult murine bone marrow cells with several monoclonal
      antibodies and separated them by magnetic cell sorting. SICs were abundant in the
      c-kit(+), Sca-1(+), CD34(+), VCAM-1(+), c-fms(+), and Mac-1(-) populations. SICs
      were recovered in the lineage-negative (Lin(-)) cells but not the Lin(+) cells.
      When macrophage colony-stimulating factor (M-CSF) was absent from the culture
      medium, no stromal colony appeared among the populations enriched in SICs. Based
      on these findings, the cells negative for lineage markers and positive for c-fms
      (M-CSF receptor) were further divided on the basis of the expression of c-kit,
      VCAM-1, Sca-1 or CD34 with a fluorescence-activated cell sorter. SICs were found
      to be enriched in the Lin(-)c-fms(+)c-kit(low) cells and Lin(-)c-fms(+)VCAM-1(+)
      cells but not in Lin(-)c-fms(+)Sca-1(+) cells and Lin(-)c-fms(+)CD34(low) cells.
      As a result, the SICs were found to be present at highest frequency in Lin(-)c
      fms(+)c-kit(low)VCAM-1(+) cells: a mean of 64% of the SICs in the Lin(-) cells
      were recovered in the population. In morphology and several characteristics, the
      stromal cells derived from Lin(-)c-fms(+)c-kit(low)VCAM-1(+) cells resembled
      fibroblastic cells. The number of Lin(-)c-fms(+)c-kit(low)VCAM-1(+) cells in bone
      marrow of mice injected with M-CSF was higher than that in control mice. In this
      study, we identified SICs as Lin(-)c-fms(+)c-kit(low)VCAM-1(+) cells and
      demonstrated that M-CSF had the ability to increase the cell population in vivo.

PMID- 11573204
TI  - Surface protein characterization of human adipose tissue-derived stromal cells.
AB  - Human bone marrow stromal cells are a multipotent population of cells capable of
      differentiating into a number of mesodermal lineages as well as supporting
      hematopoeisis. Their distinct protein and gene expression phenotype is well
      characterized in the literature. Human adipose tissue presents an alternative
      source of multipotent stromal cells. In this study, we have defined the phenotype
      of the human adipose tissue-derived stromal cells in both the differentiated and
      undifferentiated states. Flow cytometry and immunohistochemistry show that human
      adipose tissue-derived stromal cells have a protein expression phenotype that is
      similar to that of human bone marrow stromal cells. Expressed proteins include
      CD9, CD10, CD13, CD29, CD34, CD44, CD 49(d), CD 49(e), CD54, CD55, CD59, CD105,
      CD106, CD146, and CD166. Expression of some of these proteins was further
      confirmed by PCR and immunoblot detection. Unlike human bone marrow-derived
      stromal cells, we did not detect the STRO-1 antigen on human adipose tissue
      derived stromal cells. Cells cultured under adipogenic conditions uniquely
      expressed C/EBPalpha and PPARdelta, two transcriptional regulators of
      adipogenesis. Cells cultured under osteogenic conditions were more likely to be
      in the proliferative phases of the cell cycle based on flow cytometric analysis
      of PCNA and Ki67. The similarities between the phenotypes of human adipose tissue
      derived and human bone marrow-derived stromal cells could have broad implications
      for human tissue engineering.

PMID- 11573205
TI  - Actin filament assembly and actin-myosin contractility are necessary for
      anchorage- and EGF-dependent activation of phospholipase Cgamma.
AB  - Formation of actin stress fibers and the focal adhesion complex between cell and
      the substratum are crucial for nonmalignant cells to achieve anchorage-dependent
      growth. We show here that the adhesion complex formed in normal human mammary
      epithelial (HME) cells which adhered to type IV collagen, involved the EGF
      receptor (EGFR) and phospholipase Cgamma (PLCgamma) as signaling molecules, in
      addition to integrin beta1, alpha-actinin, and actin even before stimulation of
      the cells with EGF. Stimulation of cells with EGF induced tyrosine
      phosphorylation of EGFR and activation of PLCgamma, as assessed by the production
      of a second messenger diacylglycerol (DAG), without any significant increase in
      the amount of EGFR-bound PLCgamma. Disruption of either actin filaments by
      cytochalasin D (CD) or actin-myosin contractility by ML-7, an inhibitor of myosin
      light chain kinase (MLCK), altered the flattened morphology of quiescent cells to
      a retracted one, without affecting the association between EGFR and PLCgamma.
      Stimulation of CD- or ML-7-treated cells with EGF failed to inhibit tyrosine
      phosphorylation of EGFR and its association and colocalization with PLCgamma, but
      inhibited the PLCgamma activation. Phosphatidylinositol 4,5-bisphosphate
      (PtdInsP2), substrate of PLCgamma, was tightly associated with alpha-actinin and
      the content of alpha-actinin-bound PtdInsP2 was reduced by treatment of cells
      with ML-7 but not with CD. The amount of PtdInsP2 bound to alpha-actinin was
      increased by the addition of EGF and this EGF-induced increase was blocked by
      either CD or ML-7. The present results suggest that anchorage-dependent EGF
      signaling in HME cells may require both actin filament assembly and actin-myosin
      contractility for the PLCgamma activation.

PMID- 11573206
TI  - Reciprocal regulation of tissue-type and urokinase-type plasminogen activators in
      the differentiation of murine preadipocyte line 3T3-L1 and the hormonal
      regulation of fibrinolytic factors in the mature adipocytes.
AB  - Adipose tissue expresses a variety of genes including tumor necrosis factor alpha
      and type-1 plasminogen activator inhibitor (PAI-1); and these factors, produced
      by adipocytes, may be associated with the risk of coronary events in obesity. In
      this study, we characterized the production of fibrinolytic factors including
      tissue-type plasminogen activator (tPA), urokinase-type PA (uPA), and PAI-1 in
      the differentiation of preadipocytes, and examined the hormonal regulation of
      these fibrinolytic factors in mature adipocytes. Mouse 3T3-L1 preadipocytes were
      employed as a model of adipocytes. Adipocyte differentiation was induced by
      insulin, dexamethasone, and 3-isobutyl-1-methyl xanthine (IBMX). alpha
      Glycerophosphate dehydrogenase (GPDH) activity and glucose transporter 4 (GLUT4)
      mRNA, indices for adipocyte maturation, were induced on Day 4, and gradually
      increased. GPDH activity reached its maximum level on Day 14. The level of tPA, a
      major PA in preadipocytes, dramatically decreased with differentiation. On the
      other hand, that of uPA reciprocally increased. PAI-1 production was also
      dramatically induced concomitant with differentiation. In mature adipocytes, uPA
      production was dominant (25 microg/ml/24 h vs. 0.8 microg/ml/24 h for tPA). Total
      PA activity in the mature adipocytes was reduced by insulin or dexamethasone, but
      not by glucagon. Insulin, IBMX, and dexamethasone significantly decreased both
      uPA and tPA production, and increased PAI-1 production. Glucagon had no effect on
      the production of these fibrinolytic factors. Our results reveal that uPA is one
      of the markers for the differentiation of 3T3-L1 cells and that insulin, IBMX,
      and dexamethasone are potent regulators of the fibrinolytic activity in
      differentiated 3T3-L1 cells, reciprocally affecting PA and PAI-1 levels in them.

PMID- 11573207
TI  - Adhesion of epithelial cells to fibronectin or collagen I induces alterations in
      gene expression via a protein kinase C-dependent mechanism.
AB  - Adhesion of human salivary gland (HSG) epithelial cells to fibronectin- or
      collagen I gel-coated substrates, mediated by beta1 integrins, has been shown to
      upregulate the expression of more than 30 genes within 3-6 h. Adhesion of HSG
      cells to fibronectin or collagen I for 6 h also enhanced total protein kinase C
      (PKC) activity by 1.8-2.3-fold. HSG cells expressed PKC-alpha, gamma, delta,
      epsilon, mu, and zeta. Adhesion of HSG cells to fibronectin or collagen I
      specifically activated PKC-gamma and PKC-delta. Cytoplasmic PKC-gamma and PKC
      delta became membrane-associated, and immunoprecipitated PKC-gamma and PKC-delta
      kinase activities were enhanced 2.5-4.0-fold in HSG cells adherent to fibronectin
      or collagen I. In addition, adhesion of fibronectin-coated beads to HSG
      monolayers co-aggregated beta1 integrin and PKC-gamma and PKC-delta but not other
      PKC isoforms. Thus, integrin-dependent adhesion of HSG cells to fibronectin or
      collagen I activated PKC-gamma and PKC-delta. The role of this PKC upregulation
      on adhesion-responsive gene expression was then tested. HSG cells were treated
      with the specific PKC inhibitor bisindolylmaleimide I, cultured on non-precoated,
      fibronectin- or collagen I-coated substrates, and analyzed for changes in
      adhesion-responsive gene expression. Bisindolylmaleimide I strongly inhibited the
      expression of seven adhesion-responsive genes including calnexin, decorin, S
      adenosylmethionine decarboxylase, steroid sulfatase, and 3 mitochondrial genes.
      However, the expression of two adhesion-responsive genes was not affected by
      bisindolylmaleimide I. Treatment with bisindolylmaleimide I did not affect cell
      spreading and did not significantly affect the actin cytoskeleton. These data
      suggest that adhesion of HSG cells to fibronectin or collagen I induces PKC
      activity and that this induction contributes to the upregulation of a variety of
      adhesion-responsive genes.

PMID- 11573208
TI  - Characterization of C/EBPbeta isoforms in normal versus neoplastic mammary
      epithelial cells.
AB  - A member of the CCAAT Enhancer Binding Proteins (C/EBPs) family of transcription
      factors, C/EBPbeta, has recently proven to be an important player in both growth
      and differentiation of the epithelial cells in the mammary gland. When the gene
      for C/EBPbeta is disrupted in mice, these mice fail to either develop normal
      mammary ducts during puberty or pregnancy, or to lactate upon parturition.
      C/EBPbeta can be present in cells in three isoforms: C/EBPbeta-1, -2, and -3.
      These isoforms have the same carboxy terminus but different N-termini due to
      alternative translational initiation at three different initiator codons within
      the C/EBPbeta mRNA. Using a commercially available antibody specific to the C
      terminus of C/EBPbeta and a novel antibody specific to the N-terminus of
      C/EBPbeta-1, we have uncovered a striking difference in the forms of C/EBPbeta
      present in normal mammary epithelial cells versus breast cancer cell lines.
      C/EBPbeta- 1 is found exclusively in normal mammary epithelial cells, whereas
      C/EBPbeta- 2 is found only in dividing cells, both normal and neoplastic. Our
      preliminary data suggest that the prevalent form of C/EBPbeta in cancer cells,
      C/EBPbeta- 2, can activate genes which push the cell to divide, such as cyclin
      D1.

PMID- 11573209
TI  - Enhanced proliferation and differentiation of rat hepatocytes cultured with bone
      marrow stromal cells.
AB  - Liver transplantation is the only clinically effective method of treating acute
      liver failure. However, wider application of this therapeutic modality is
      restricted primarily by shortage of donor organs. In the search for alternative
      methods of liver replacement therapy, investigators have focused on
      transplantation of normal allogeneic hepatocytes and on the development of liver
      support systems utilizing isolated hepatocytes. Since all human livers suitable
      for cell harvest are being used for transplantation, hepatocyte therapy using
      human tissue would require growing of cells in vitro. Unfortunately, although
      hepatocytes have tremendous capacity to proliferate in vivo, their ability to
      grow in culture is severely limited. Stromal cells from bone marrow and other
      blood-forming organs have been found to support hematopoiesis. In this paper, we
      show that bone marrow-derived stromal cells (BMSCs) enhance proliferation and
      support differentiation of rat hepatocytes in culture. Further, we demonstrate
      that in hepatocyte/BMSC co-cultures, clonal expansion of small hepatocytes (SH)
      is increased. Using semipermeable membrane cultures, we established that direct
      cell-cell contact is necessary for stimulation of cell proliferation. We also
      show that BMSCs which are in direct contact with hepatocytes and SH colonies
      express Jagged1. This suggests a potential role for Notch signaling in the
      observed effects. Finally, we present evidence that the expression and activity
      of liver specific transcription factors, CCAAT/enhancer binding proteins and
      liver specific key enzymes such as tryptophan 2,3-dioxygenase, are improved in
      hepatocyte/BMSC co-cultures. In conclusion, results of this study indicate that
      BMSCs could facilitate proliferation and differentiation of primary rat
      hepatocytes and their progenitors (SH) in vitro.

PMID- 11573221
TI  - Optical properties of native and coagulated porcine liver tissue between 400 and
      2400 nm.
AB  - BACKGROUND AND OBJECTIVE: Laser induced thermotherapy (LITT) is a promising
      treatment for irresectable liver tumors. For predicting the effects of laser
      applications and optimizing irradiation planning in LITT, knowledge about light
      distribution in tissue, optical tissue properties (absorption, scattering,
      anisotropy, penetration depth) and their changes due to thermal denaturation is
      indispensable. STUDY DESIGN/MATERIALS AND METHODS: The optical parameters in
      healthy porcine liver were determined in the native state and after thermal
      coagulation using a double integrating sphere system in the wavelength range of
      400-2400 nm. RESULTS: Optical parameters showed significant fluctuations in the
      examined wavelength range mainly due to the water and hemoglobin content in the
      tissue. The greatest optical penetration depth of 7.46 mm was achieved at 1070
      nm. After thermal coagulation, a clear increase in scattering and a slight
      decrease in absorption was found, which results in a decreased optical
      penetration depth. CONCLUSIONS: In order to ensure a safe and effective
      procedure, an adjustment of the laser power to the decreasing penetration depth
      is recommended during therapy. These results provide a better understanding of
      laser-tissue interaction and may be helpful to investigators in the field of
      light dosimetry in liver tissue.

PMID- 11573222
TI  - Use of osmotically active agents to alter optical properties of tissue: effects
      on the detected fluorescence signal measured through skin.
AB  - BACKGROUND AND OBJECTIVE: Hyper-osmotic chemical agents were used to study the
      effects of transient tissue scattering on the remitted fluorescence emission
      intensity from a target placed under a tissue sample. STUDY DESIGN/MATERIALS AND
      METHODS: A fluorescent film was placed underneath in vitro and in vivo samples of
      hamster skin, and the remitted fluorescent signal traveling to the tissue surface
      was monitored over time as the tissue was treated with an osmotically active
      agent. RESULTS: The detected fluorescent signal increased as the scattering in
      tissue samples was substantially reduced. The increase was greater for dimethyl
      sulfoxide than glucose or glycerol. It was not statistically different between in
      vivo skin and in vitro skin. CONCLUSION: The study shows how chemical agents can
      be used to improve the detected signal for a specific optical application. It
      could be useful in a number of optical therapeutic and diagnostic applications
      that can benefit from an increase in the penetration depth of light.

PMID- 11573223
TI  - Residual heat deposition in dental enamel during IR laser ablation at 2.79, 2.94,
      9.6, and 10.6 microm.
AB  - BACKGROUND AND OBJECTIVE: The principal factor limiting the rate of laser
      ablation of dental hard tissue is the risk of excessive heat accumulation in the
      tooth. Excessive heat deposition or accumulation may result in unacceptable
      damage to the pulp. The objective of this study was to measure the residual heat
      deposition during the laser ablation of dental enamel at those IR laser
      wavelengths well suited for the removal of dental caries. Optimal laser ablation
      systems minimize the residual heat deposition in the tooth by efficiently
      transferring the deposited laser energy to kinetic and internal energy of ejected
      tissue components. STUDY DESIGN/MATERIALS AND METHODS: The residual heat
      deposition in dental enamel was measured at laser wavelengths of 2.79, 2.94, 9.6,
      and 10.6 microm and pulse widths of 150 nsec -150 microsec using bovine block
      "calorimeters." Water droplets were applied to the surface before ablation with
      150 microsec Er:YAG laser pulses to determine the influence of an optically thick
      water layer on reducing heat deposition. RESULTS: The residual heat was at a
      minimum for fluences well above the ablation threshold where measured values
      ranged from 25-70% depending on pulse duration and wavelength for the systems
      investigated. The lowest values of the residual heat were measured for short (<
      20 micros) CO(2) laser pulses at 9.6 microm and for Q-switched erbium laser
      pulses at 2.79 and 2.94 microm. Droplets of water applied to the surface before
      ablation significantly reduced the residual heat deposition during ablation with
      150 microsec Er:YAG laser pulses. CONCLUSIONS: Residual heat deposition can be
      markedly reduced by using CO(2) laser pulses of less than 20 microsec duration
      and shorter Q-switched Er:YAG and Er:YSGG laser pulses for enamel ablation.

PMID- 11573224
TI  - Treatment of rhinophyma with Er:YAG laser.
AB  - BACKGROUND AND OBJECTIVE: Rhinophyma is a benign, disfiguring disorder of the
      nose which presents the end stage of acne rosacea, and can also occasionally
      result in nasal airway obstruction. We describe the first series of patients
      treated with Erbium laser. STUDY DESIGN/MATERIALS AND METHODS: Severe-to-moderate
      rhinophyma in six patients were treated at our institution between 1995 and 1996,
      using the Erbium:YAG (Erb:YAG) laser. RESULTS: All patients achieved marked
      cosmetic improvement, with no complications. Post-operative healing time was
      seven to fourteen days-significantly shorter than similar other modalities.
      CONCLUSIONS: The Erbium laser provides very accurate tissue ablation and allows
      the sculpturing of the hypertrophied areas, offering good cosmetic results, with
      a very short healing period as shown in our study.

PMID- 11573225
TI  - Carbon dioxide laser skin resurfacing with a cooled handpiece.
AB  - BACKGROUND AND OBJECTIVE: Carbon dioxide (CO(2)) laser skin resurfacing has
      become an accepted procedure for the rejuvenation of aged and wrinkled facial
      skin. The benefits of this technique have been limited by the prolonged
      postoperative erythema, delayed re-epithelialization, and potential changes in
      pigmentation. We investigated the effects of coupling a pulsed CO(2) laser to a
      zinc selenide handpiece at various temperatures to cool and conduct heat from the
      skin surface. We compared the heat conducting handpiece to standard techniques
      used to determine the effects on epithelial preservation, depth of thermal
      damage, and new collagen growth. STUDY DESIGN/MATERIALS AND METHODS: The dorsal
      aspect of piglets was treated with four handpiece arrangements: no thermally
      conducting window; a zinc selenide thermally conducting window at room
      temperature; and the zinc selenide thermally conducting window cooled to 10 and 5
      degrees C. Intensities were measured to account for reflections from the surface
      of the handpiece. With the CO(2) laser in scanning mode and a spot size of 1 mm,
      each handpiece was used at intensities ranging from 8-30 W in one pass. Biopsies
      for histopathologic analysis and determination of the degree of epithelial damage
      and the depth of thermal damage were taken on days 0, 2, and 16. RESULTS: All
      specimens revealed complete re-epithelialization by day 16. The addition of a
      cooled handpiece did not affect either the amount of epithelial preservation or
      the depth of thermal damage. CONCLUSIONS: There is no significant advantage in
      using a cooled or room temperature zinc selenide handpiece for epithelial
      preservation or decreasing the inflammatory response in CO(2) laser resurfacing.

PMID- 11573226
TI  - Treatment of recalcitrant-pigmented flat warts using frequency-doubled Q-switched
      Nd-YAG laser.
AB  - BACKGROUND AND OBJECTIVE: Recalcitrant-pigmented flat warts may persist for years
      despite treatment. Many methods have been used to manage pigmented flat warts,
      but their efficiencies are varied. Since pigmented flat warts are very similar to
      lentigo clinically, we used frequency-doubled Q-switched (FDQS) Nd-YAG laser at
      the wavelength of 532 nm to treat recalcitrant-pigmented flat warts and evaluated
      the effect. STUDY DESIGN/MATERIALS AND METHODS: Seven patients with recalcitrant
      pigmented flat warts were enrolled in this study. We set the FDQS Nd-YAG laser to
      deliver 2.5 J/cm(2) fluence at the wavelength of 532 nm to treat these lesions.
      After 6 months, we evaluated the recurrence of pigmented flat warts, pigmentary,
      and textural changes on the treated areas. RESULTS: There were absences of
      recurrent lesions, pigmentary, and textural changes on the treated areas of these
      seven patients after 6 months. CONCLUSIONS: Through both selective
      photothermolysis effect and propagation of photoacoustic waves, FDQS Nd-YAG laser
      at the wavelength of 532 nm can be used as an effective alternative to treat
      recalcitrant pigmented flat warts.

PMID- 11573227
TI  - Treating REM syndrome with the pulsed dye laser.
AB  - BACKGROUND AND OBJECTIVE: REM syndrome (reticular erythematous mucinosis) is a
      benign but bothersome skin disease that common occurs in middle age and among
      women. Local and systemic treatment measures are often associated with a high
      rate of side effects and relapses are common. We evaluated the pulsed dye laser
      as an alternative method because of its good efficacy in vascular skin diseases.
      STUDY DESIGN/MATERIALS AND METHODS: We treated two female patients with REM
      syndrome using the pulsed dye laser. RESULTS: In both patients the erythematous
      skin changes were almost completely removed after five and three laser sessions,
      respectively. Other than transient hypopigmentation, no side effects occurred. In
      one case there is still no evidence of recurrence 6 years after a trial treatment
      was conducted. In the same patient, clinical success was histologically
      confirmed. CONCLUSIONS: This is the first report on the successful treatment of
      REM syndrome of two female patients with the pulsed dye laser.

PMID- 11573228
TI  - Skin protection for photosensitized patients.
AB  - BACKGROUND AND OBJECTIVE: The goal of this study was to evaluate various creams
      for their capability to protect photosensitized skin from visible light. STUDY
      DESIGN/MATERIALS AND METHODS: Two cover creams and creams containing various
      combinations of Vaseline with TiO(2), ZnO, and Fe(2)O(3) were used to measure the
      reduced light transmission and the light absorption spectrum. In vitro and in
      vivo tests were performed to assess the protection from light by above mentioned
      compounds. RESULTS: The cover creams and the 50% TiO(2) cream showed similar
      efficacy in reducing light transmission, while the sunscreen was less efficient
      by a factor of 5. Cell protection by 25% TiO(2)+25% ZnO, TiO(2), or the cover
      creams was more efficient than protection by the sunscreen or other compounds. In
      vivo, the dark cover cream protected the skin by a factor of 3.4 better than the
      sunscreen. CONCLUSION: The dark cover cream has acceptable properties to protect
      photosensitized skin.

PMID- 11573229
TI  - Xanthelasma palpebrarum: treatment with the erbium:YAG laser.
AB  - BACKGROUND AND OBJECTIVE: Xanthelasma palpebrarum presents a therapeutic and
      aesthetic challenge because of its high visibility and frequent rate of
      recurrence with a wide variety of treatments. Many patients are disappointed by
      an initial unsuccessful treatment and fail to return for further therapy until
      the skin problem has become quite conspicuous. A simple treatment with few side
      effects and good acceptance remains an important goal. STUDY DESIGN/MATERIALS AND
      METHODS: Fifteen patients with a total of 33 xanthelasma lesions, were treated by
      an erbium:YAG laser. The follow-up period of observation was between seven and
      twelve months. RESULTS: All lesions were removed without hyperpigmentation or
      scarring. CONCLUSIONS: The erbium:YAG laser represents an effective means for
      treating xanthelasmas with few side effects.

PMID- 11573230
TI  - Laser soldering of rat skin, using fiberoptic temperature controlled system.
AB  - BACKGROUND AND OBJECTIVE: Laser soldering of tissues is based on the application
      of a biological solder on the approximated edges of a cut. Our goal was to use
      laser soldering for sealing cuts in skin under temperature feedback control and
      compare the results with ones obtained using standard sutures. STUDY
      DESIGN/MATERIALS AND METHODS: Albumin solder was applied onto the approximated
      edges of cuts created in rat skin. A fiberoptic system was used to deliver the
      radiation of a CO(2) laser, to heat a spot near the cut edges, and to control the
      temperature. Laser soldering was carried out, spot by spot, where the temperature
      at each spot was kept at 65-70 degrees C for 10 sec. RESULTS: The tensile
      strength of laser-soldered cuts was measured after 3-28 days postoperatively and
      was found comparable to that of sutured cuts. Histopathological studies showed no
      thermal damage and less inflammatory reaction than that caused by standard
      sutures (P = 0.04). CONCLUSIONS: Temperature controlled laser soldering of cuts
      in rat skin gave strong bonding. The cosmetic and histological results were very
      good, in comparison to those of standard sutures.

PMID- 11573231
TI  - Cell attachment to extracellular matrices is modulated by pulsed radiation at 820
      nm and chemicals that modify the activity of enzymes in the plasma membrane.
AB  - BACKGROUND AND OBJECTIVES: Adhesive interactions between cells and extracellular
      matrices play a regulative role in wound repair processes. The objective of this
      investigation is to study action mechanisms of pulsed radiation at 820 nm on
      cellular adhesion in vitro. Light emitting diodes (LED) at 820 nm are widely used
      for treatment of wounds of various etiology. STUDY DESIGN/MATERIALS AND METHODS:
      The LED (820 +/- 10 nm, 10 Hz, 16-120 J/m(2)) is used for the irradiation of HeLa
      cell suspension. In parallel experiments, amiloride (5 x 10(-4) M), ouabain (7 x
      10(-5) M, 7 x 10(-4) M), quinacrine (6 x 10(-4) M), arachidonic acid (1 x 10(-5)
      M), glucose (2 x 10(-4) M), and ATP (5 x 10(-5) M) are added to the cell
      suspension before or after the irradiation procedure. The cell-glass adhesion is
      studied using the adhesion assay technique described in Lasers Surg Med 1996;
      18:171. RESULTS: Cell-glass adhesion increases in a dose-dependent manner
      following the irradiation. Preirradiation eliminates the inhibition of cell
      attachment caused by ouabain, arachidonic acid, and ATP. The inhibitive effect of
      quinacrine on the cell attachment is eliminated by the irradiation performed
      after the treatment with the chemical. Irradiation and amiloride have a
      synergetic stimulative effect on the cell attachment. The threshold dose for the
      cell attachment stimulation by the irradiation is decreased by the treatment of
      the cell suspension with amiloride or ouabain. CONCLUSIONS: The results obtained
      indicate that pulsed IR radiation at 820 nm increases the cell-matrix attachment.
      It is the modulation of the monovalent ion fluxes through the plasma membrane and
      not the release of arachidonic acid that is involved in the cellular signaling
      pathways activated by irradiation at 820 nm. Preirradiation has a protective
      effect against the inhibitive action of ouabain, arachidonic acid, ATP, and
      quinacrine on cell attachment process. It is supposed that irradiation activates
      those signaling pathways in cells which attenuate the inhibitive action of these
      chemicals.

PMID- 11573232
TI  - Use of a new ICG-dye-enhanced diode laser for percutaneous laser disc
      decompression.
AB  - BACKGROUND AND OBJECTIVE: The lasers used today for Percutaneous Laser Disc
      Decompression (PLDD) can not selectively ablate the nucleus pulposus (NP). We
      hypothesized that if indocyanine green dye were injected into the NP, 805 nm
      diode laser irradiation would result in selective and safe removal of NP tissue
      without damaging nearby tissues. STUDY DESIGN/MATERIALS AND METHODS: Twelve
      beagle dogs were used for three experiments, i.e., determination of attenuation
      coefficients of NP and AF, determination of weight of NP before and after laser
      irradiation, and histopathological study. RESULTS: The attenuation coefficient at
      805 nm of NP which had been homogenized in the presence of ICG was 2521.3/cm.
      Upon application of the diode laser at a power of 1, 3, or 5 W (the intensity of
      laser irradiation: 0.353, 1.061, or 1.768 x 10(3) W/cm(2)) to NPs into which ICG
      had been injected, the weight of the NPs decreased by a mean 20, 45, and 65%,
      respectively. Macroscopic and microscopic examination of the discs after PLDD
      showed that only the NP where the tissues were stained by ICG were removed.
      CONCLUSIONS: These results indicated that the combined use of ICG and diode laser
      irradiation effectively and selectively ablates the NP with low laser power.

PMID- 11573233
TI  - Simple organ cornea culture model for re-epithelialization after in vitro excimer
      laser ablation.
AB  - BACKGROUND AND OBJECTIVE: Most of the in vitro work to characterize the effects
      of clinical laser surgery on corneal tissues has concentrated on the effects on
      stromal keratocytes and endothelium with little attention being paid to corneal
      epithelium. Our purpose is to describe the epithelial healing rates observed in
      freshly cultured rabbit corneas treated with phototherapeutic keratectomy (PTK).
      STUDY DESIGN/MATERIALS AND METHODS: Corneas were placed in a simple organ culture
      system, with media change every 2 days. A clinical excimer laser was used to
      perform a 6 mm diameter, 100 microm depth transepithelial PTK on 24 cultured
      rabbit corneas, 1 day after culture initiation. For each post-treatment day, one
      experimental and one control cornea were removed from culture and stained with
      fluorescein, photographed, and fixed for histology. Epithelial defect area was
      measured with digital imaging software and analyzed statistically to assess the
      re-epithelialization rate. RESULTS: Control corneas, maintained in culture for 1
      4 days, had no epithelial defects. Those corneas treated with PTK exhibited an
      immediate epithelial defect that slowly healed over 3 days. This was confirmed on
      histopathological analysis. A significant linear trend in re-epithelialization
      across the time points studied was found (F = 80.48, P = 0.0029). The slope of
      the linear regression model showed an estimate rate of re-epithelialization of 
      6.70 over the 3 days. CONCLUSION: We have described the development of a simple,
      whole organ, rabbit cornea culture model for re-epithelialization after PTK. Our
      rates of epithelial healing resemble those found in the literature in live rabbit
      models. Therefore, this model may possibly be used to monitor epithelial wound
      healing in different corneal diseases or injuries.

PMID- 11573235
TI  - Putative basal lateral membrane receptors for 24,25-dihydroxyvitamin D(3) in carp
      and Atlantic cod enterocytes: characterization of binding and effects on
      intracellular calcium regulation.
AB  - The vitamin D metabolite, 24R,25-dihydroxyvitamin D(3) (24R,25(OH)(2)D(3)), was
      tested for its ability to specifically bind to basal lateral membranes isolated
      from intestinal epithelium of Atlantic cod (a seawater fish), carp (a freshwater
      fish), and chicken. Specific saturable binding was demonstrated in membranes from
      all three species. Membranes from Atlantic cod, carp, and chicken revealed K(d)'s
      of 7.3 +/- 0.9, 12.5 +/- 0.9 and 7.8 +/- 0.1 nM, and a B(max) for each species
      estimated to 57.9 +/- 2.9, 195.1 +/- 8.4 and 175 +/- 0.8 fmol/mg protein,
      respectively. Scatchard analyses indicated a convex curvature and Hill analyses
      revealed apparent Hill coefficients of 1.84 +/- 0.28, 1.80 +/- 0.29, and 1.78 +/-
      0.27 for Atlantic cod, carp and chicken, suggesting a positive cooperative
      binding in all three species. Basal lateral membranes from Atlantic cod and carp
      were used to further characterize the binding moiety. In competition studies,
      basal lateral membranes from Atlantic cod or carp did not discriminate between
      24R,25(OH)(2)D(3) and the 24S,25(OH)(2)D(3) isomer, whereas, 1,25(OH)(2)D(3) and
      25(OH)D(3), were less effective in competing with [(3)H]24R,25(OH)(2)D(3) for
      binding to basal lateral membranes in Atlantic cod and carp. In both the Atlantic
      cod and carp enterocyte basal lateral membranes, the binding activity could be
      extracted equally well with high salt as with detergent, indicating a peripheral
      membrane protein rather than an integral membrane binding protein. Finally,
      isolated Atlantic cod and carp enterocytes were chosen for analyses of signal
      transduction events mediated by the putative receptor. In both species,
      24R,25(OH)(2)D(3) but not 24S,25(OH)(2)D(3), suppressed Ca(2+)-uptake by
      enterocytes in a dose-dependent manner. Enterocytes from Atlantic cod and carp,
      acclimated to Ca(2+)-free media, responded by an intracellular Ca(2+)-release
      within seconds after addition of 24R,25(OH)(2)D(3) or 24S,25(OH)(2)D(3). The
      effects on intracellular Ca(2+)-release were dose-dependent for both metabolites.
      24S,25(OH)(2)D(3) was effective at lower concentrations and triggered a higher
      response compared to 24R,25(OH)(2)D(3). These results suggest that the binding
      molecule(s) for 24R,25(OH)(2)D(3) and 24S,25(OH)(2)D(3) is/are capable of acting
      as a receptor, mediating rapid, non-genomic responses in intestinal cells.

PMID- 11573236
TI  - Possible involvement of protein kinase C in the induction of adipose
      differentiation-related protein by Sterol ester in RAW 264.7 macrophages.
AB  - The accumulation of lipid droplets in macrophages contributes to the formation of
      foam cells, an early event in atherosclerosis. It is, therefore, important to
      elucidate the mechanisms by which lipid droplets accumulate and are utilized.
      Sterol ester (SE)-laden RAW 264.7 macrophages accumulated lipid droplets in a
      time-dependent manner up to 16 h, which was enhanced by cotreatment with 0.1
      microM phorbol 12-myristate 13-acetate (PMA). Inhibition of protein kinase C
      (PKC) activity by cotreatment with 0.3 microM calphostin C CAL for 16 h resulted
      in coalescence of small lipid droplets into large ones and increased accumulation
      of lipid droplets, although to a lesser extent than after PMA cotreatment.
      Immunostaining for adipose differentiation-related protein (ADRP) revealed a
      fluorescent rim at the surface of each medium to large lipid droplet. ADRP
      appearance correlated with lipid droplet accumulation and was regulated by PMA in
      a time-dependent manner. Induction of ADRP expression by PMA or CAL required SE,
      since ADRP levels in PMA- or CAL-treated non-SE-laden macrophages were comparable
      to those in untreated cells. Removal of SE from the incubation medium resulted in
      the concomitant dissolution of lipid droplets and down-regulation of ADRP. In
      conclusion, the above results suggest that ADRP may be an important protein in
      the regulation of lipid droplet metabolism in lipid-laden macrophages and that
      this regulation may be mediated by PKC activity.

PMID- 11573237
TI  - Novel role of extracellular carbon dioxide in lymphocyte proliferation in
      culture.
AB  - CO(2)/HCO(3)(-) buffering system is indispensable to maintain the pH of culture
      media for long-term cell culture. Now-a-days, the zwiterionic hydrogen buffer
      HEPES is widely used as an additional buffer in the commonly used culture media.
      There are reports on the successful use of HEPES-buffered media, under
      CO(2)/HCO(3)(-) free conditions, for long-term cell cultures. However, still
      CO(2)/HCO(3)(-) buffering system is widely used. We aimed at investigating the
      reason for this. We found that lymphocytes proliferate in response to
      concanavalin A only in HCO(3)(-)-buffered medium in the presence of 5% CO(2), but
      not in the HEPES-buffered medium in the absence of CO(2). However, lymphocyte
      proliferation was observed in HEPES-buffered medium in the presence of 5% CO(2)
      and in the absence of HCO(3)(-). On the other hand, a low level proliferation was
      observed in HEPES-buffered medium supplemented with HCO(3)(-) in the absence of
      CO(2). Supplementation of the culture medium with TCA cycle intermediates and the
      precursors for the salvage pathway of nucleotide synthesis did not support the
      lymphocyte proliferation at all. Based on these findings and other reports, we
      suggest that extracellular CO(2) plays a novel role in cell proliferation.

PMID- 11573238
TI  - Regulated expression of GRP78 during vasopressin-induced hypertrophy of heart
      derived myocytes.
AB  - Although the development of cellular hypertrophy is widely believed to involve
      Ca(2+) signaling, potential supporting roles for sequestered Ca(2+) in this
      process have not been explored. H9c2 cardiomyocytes respond to arginine
      vasopressin with an initial mobilization of Ca(2+) stores and reduced rates of
      mRNA translation followed by repletion of Ca(2+) stores, up-regulation of
      translation beyond initial rates, and the development of hypertrophy. Rates of
      synthesis of the endoplasmic reticulum (ER) chaperones, GRP78 and GRP94, were
      found to increase preferentially at early times of vasopressin treatment. Total
      GRP78 content increased 2- to 3-fold within 8 h after which the chaperone was
      subject to post-translational modification. Preferential synthesis of GRP78 and
      the increase in chaperone content both occurred at pM vasopressin concentrations
      and were abolished at supraphysiologic Ca(2+) concentrations. Co-treatment with
      phorbol myristate acetate decreased vasopressin-dependent Ca(2+) mobilization and
      slowed appearance of new GRP78 molecules in response to the hormone, whereas 24 h
      pretreatment with phorbol ester prolonged vasopressin-dependent Ca(2+)
      mobilization and further increased rates of GRP78 synthesis in response to the
      hormone. Findings did not support a role for newly synthesized GRP78 in
      translational up-regulation by vasopressin. However up-regulation, which does not
      depend on Ca(2+) sequestration, appeared to expedite chaperone expression. This
      report provides the first evidence that a Ca(2+)-mobilizing hormone at
      physiologic concentrations signals increased expression of GRP78. Translational
      tolerance to depletion of ER Ca(2+) stores, typifying a robust ER stress
      response, did not accompany vasopressin-induced hypertrophy.

PMID- 11573239
TI  - Specificity of SAF-A and lamin B binding in vitro correlates with the satellite
      DNA bending state.
AB  - There is evidence that Matrix Attachment Region (MAR)-binding proteins also bind
      satellite DNA (satDNA). The aim of the current work was to determine whether the
      major nuclear matrix (NM) MAR-binding proteins are able to recognize satDNAs of
      different locations and what DNA structural features are important for the
      recognition. In nuclei and NM, a number of the same polypeptides were recognized
      on a southwestern blot when MAR of immunoglobulin kappa gene (Ig kappa MAR) and
      pericentromeric (periCEN) satDNA fragments were used. However, the binding
      decreased dramatically when human and mouse CEN satDNA were used for the probes.
      After an NM extract was subjected to ion exchange chromatography, the main DNA
      binding proteins were identified as SAF-A (scaffold attachment factor A) and
      lamin B. It was not possible to test the binding of lamin B by gel mobility shift
      assay (GMSA), but SAF-A showed an ability to distinguish CEN and periCEN satDNA
      fragments in GMSA. While periCEN fragments have an abnormally slow mobility on
      electrophoresis, which is a hallmark of bent DNA, CEN satDNA fragments have a
      normal mobility. A computer analysis was done using the wedge model (Ulanovsky
      and Trifonov [1987] Nature 326:720-722), which describes how the curved state
      depends on particular nucleotide sequences. The curved states of the fragments
      predicted by the model are in good agreement with their ability to be recognized
      by NM proteins. Thus SAF-A and lamin B are able to recognize conserved structural
      features of satDNA in the same way that MAR-binding proteins recognize MARs in
      spite of a lack of a consensus sequence. CEN and periCEN satDNAs are
      distinguished by proteins in correlation with the helical curvature of these
      fragments.

PMID- 11573240
TI  - Butyrate stimulates ApoA-IV-containing lipoprotein secretion in differentiated
      Caco-2 cells: role in cholesterol efflux.
AB  - The aim of this study was to determine: (1) whether the Short Chain Fatty Acids
      (SCFA) Acetate, Propionate, and Butyrate enhance the synthesis and secretion of
      intestinal apolipoprotein A-IV-containing lipoproteins and (2) if so, whether
      these particles are able to promote cholesterol efflux in vitro. For this purpose
      Caco-2 cells were used for their functional properties of differentiated
      enterocytes. They were incubated with the three SCFA (2, 4, and 8 mM) for 48 h.
      Only butyrate stimulated apoA-IV gene expression and this was associated with an
      increase in apoA-IV secretion. A nondenaturing 2D-PAGE (agarose gel was followed
      by PAGE) was used to identify apoA-IV-containing lipoproteins in various media,
      and showed that butyrate stimulated the secretion of two small HDL sized
      particles. The influence of these secreted particles on cholesterol efflux was
      investigated using incubation of media with (3)H-cholesterol-labeled Fu5AH cells.
      The data indicate that conditioned media from Caco-2 cells treated with butyrate
      resulted in an increase of 20-30% in cholesterol efflux. We conclude that
      butyrate may regulate apoA-IV secretion and, therefore, modulate reverse
      cholesterol transport.

PMID- 11573241
TI  - Keratinocyte differentiation inversely regulates the expression of involucrin and
      transforming growth factor beta1.
AB  - Extensive skin loss from a variety of conditions such as severe thermal injury is
      associated with significant functional morbidity and mortality. In recent years,
      the healing quality has been improved for patients who suffer burns due in part
      to the usage of skin replacement mainly prepared from multi-layered sheets of
      cultured keratinocytes. Although it is known that keratinocytes are a rich source
      of wound healing promoting factors such as transforming growth factor-beta1 (TGF
      beta1), it is not clear whether differentiated keratinocytes in a multi-layer
      form release this multi-functional growth factor and has any functional influence
      on dermal fibroblasts. This study examined the hypothesis that keratinocytes in
      mono- and multi-layer forms express different levels of TGF-beta1. To address
      this hypothesis, keratinocytes were grown in serum free medium (KSFM)
      supplemented with bovine pituitary extract (50 microg/ml) and EGF (5 microg/ml).
      When cells reached confluency, conditioned medium was removed and replaced with
      50% KSFM with no additives and 50% DMEM without serum and cells were allowed to
      form multi-layers and differentiate. The conditioned medium was then collected
      every 48 h up to 24 days and the level of TGF-beta1 and the efficacy of a
      keratinocyte released fibroblast mitogenic factor were evaluated by ELISA and
      (3)H-thymidine incorporation, respectively. Northern analysis was also employed
      to evaluate the expression of TGF-beta1, involucrin, TIMP-1, and 18 S ribosomal
      RNA in keratinocytes at different times of the onset of differentiation. The
      microscopic morphology of keratinocytes at different times of induction of cell
      differentiation showed detachments (nodules) of many regions of keratinocyte
      sheet from culture substratum within 1-2 weeks. The numbers and sizes of these
      nodules were increased as the process of keratinocyte differentiation proceed.
      The results of TGF-beta1 evaluation revealed that mono-layers of cultured
      keratinocytes which were round, attached, and proliferating in KSFM + BPE and EGF
      containing medium released a significantly higher level of TGF-beta1 (196 +/- 58
      pg /ml) relative to those grown in multi-layer forms (28 +/- 7.8 pg/ml). A
      longitudinal experiment was then conducted and the results showed that cells on
      the onset of differentiation released even greater level of TGF-beta1 (388 +/- 53
      pg/ml) relative to those grown in KSFM + BPE and EGF. This finding was consistent
      with the expression of TGF-beta1 mRNA evaluated in keratinocytes grown in test
      medium for various duration. In general, the level of TGF-beta1 protein and mRNA
      gradually reduced to its lowest level within 12 days of growing cells in our test
      medium. When aliquots of the collected keratinocyte conditioned medium were added
      to dermal fibroblasts, the level of (3)H-thymidine incorporation increased only
      in those cells receiving aliquots of conditioned medium containing high levels of
      TGF-beta1. When involucrin was used as a differentiation marker for keratinocytes
      at different time points, the highest level of involucrin mRNA expression was
      found at the later stage of cell differentiation. In conclusion, high involucrin
      expressing differentiated keratinocytes seem to be quiescent in releasing both
      TGF-beta1 and a fibroblast mitogenic factor.

PMID- 11573242
TI  - Molecular cloning and characterization of a RING-H2 finger protein, ANAPC11, the
      human homolog of yeast Apc11p.
AB  - Yeast Apc11p together with Rbx1 and Roc2/SAG define a new class of RING-H2
      fingers in a superfamily of E3 ubiquitin ligases. The human homolog of Apc11p,
      ANAPC11 was identified during a large-scale partial sequencing of a human liver
      cancer cDNA library and partial characterization was performed. This 514 bp full
      length cDNA has a predicted open reading frame (ORF) encoding 84 amino acids. The
      ORF codes for ANAPC11, the human anaphase promoting complex subunit 11 (yeast
      APC11 homolog), which possesses a RING-H2 finger motif and exhibits sequence
      similarity to subunits of E3 ubiquitin ligase complexes. In Northern blot
      hybridization with poly(A) RNA of various human tissues using radio-labelled
      ANAPC11 cDNA probe, we found strong signals detected in skeletal muscle and
      heart; moderate signals detected in brain, kidney, and liver; and detectable but
      low signals in colon, thymus, spleen, small intestine, placenta, lung, and
      peripheral blood leukocyte. The ANAPC11 gene is located at the human chromosome
      17q25. ANAPC11 is distributed diffusely in the cytoplasm and nucleus with
      discrete accumulation in granular structures in all the cell lines (AML 12,
      HepG2, and C2C12) transfected. Expression level of ANAPC11 is found higher in
      certain types of cancer determined in the RNA dot blot experiment.

PMID- 11573243
TI  - Ovarian carcinoma cells synthesize both chondroitin sulfate and heparan sulfate
      cell surface proteoglycans that mediate cell adhesion to interstitial matrix.
AB  - Metastatic ovarian carcinoma metastasizes by intra-peritoneal, non-hematogenous
      dissemination. The adhesion of the ovarian carcinoma cells to extracellular
      matrix components, such as types I and III collagen and cellular fibronectin, is
      essential for intra-peritoneal dissemination. The purpose of this study was to
      determine whether cell surface proteoglycans (a class of matrix receptors) are
      produced by ovarian carcinoma cells, and whether these proteoglycans have a role
      in the adhesion of ovarian carcinoma cells to types I and III collagen and
      fibronectin. Proteoglycans were metabolically labeled for biochemical studies.
      Both phosphatidylinositol-anchored and integral membrane-type cell surface
      proteoglycans were found to be present on the SK-OV-3 and NIH:OVCAR-3 cell lines.
      Three proteoglycan populations of differing hydrodynamic size were detected in
      both SK-OV-3 and NIH:OVCAR-3 cells. Digestions with heparitinase and
      chondroitinase ABC showed that cell surface proteoglycans of SK-OV-3 cells had
      higher proportion of chondroitin sulfate proteoglycans (75:25 of chondroitin
      sulfate:heparan sulfate ratio), while NIH:OVCAR-3 cells had higher proportion of
      heparan sulfate proteoglycans (10:90 of chondroitin sulfate:heparan sulfate
      ratio). RT-PCR indicated the synthesis of a unique assortment of syndecans,
      glypicans, and CD44 by the two cell lines. In adhesion assays performed on matrix
      coated titer plates both cell lines adhered to types I and III collagen and
      cellular fibronectin, and cell adhesion was inhibited by preincubation of the
      matrix with heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, or
      chondroitin glycosaminoglycans. Treatment of the cells with heparitinase,
      chondroitinase ABC, or methylumbelliferyl xyloside also interfered with adhesion
      confirming the role of both heparan sulfate and chondroitin sulfate cell surface
      proteoglycans as matrix receptors on ovarian carcinoma cells.

PMID- 11573244
TI  - Distinct involvement of NF-kappaB and p38 mitogen-activated protein kinase
      pathways in serum deprivation-mediated stimulation of inducible nitric oxide
      synthase and its inhibition by 4-hydroxynonenal.
AB  - Cytokine-induced expression of inducible nitric oxide synthase (iNOS) and
      concomitant production of nitric oxide (NO) involve activation of mitogen
      activated protein (MAP) kinases and are in most cases mediated by the
      transcription factor NF-kappaB. We investigated the role of p38 MAP kinase
      activation and IkappaB phosphorylation in iNOS expression in a novel iNOS
      inducing model in mouse macrophages. Deprivation of serum from the culture medium
      of RAW 264.7 cells up-regulated iNOS and NO production, which were inhibited by 4
      hydroxy-2-nonenal (HNE), a component of oxidatively modified low-density
      lipoprotein (oxLDL). Serum withdrawal induced phosphorylation of Akt, IkappaB,
      and p38 MAP kinase. Pretreatment with the potent PI3 kinase inhibitor wortmannin,
      the NF-kappaB inhibitor PDTC or the specific p38 MAP kinase inhibitor SB203580
      each partially attenuated the induction of iNOS and NO production, demonstrating
      that both p38 activation and IkappaB phosphorylation are required for iNOS
      expression. SB203580, however, did not prevent the phosphorylation of Akt and
      IkappaB, suggesting that the p38 MAP kinase signal contributes to iNOS gene
      expression through an IkappaB-phosphorylation-independent pathway. HNE, which
      markedly inhibited iNOS expression and NO production, prevented the serum
      withdrawal-triggered IkappaB phosphorylation but not that of Akt or p38 MAP
      kinase. A high concentration of HNE stimulated dephosphorylation of IkappaB but
      promoted activation of p38 MAP kinase. Taken together, these results suggest that
      NF-kappaB and p38 MAP kinase lie in separate signal pathways for serum
      deprivation-stimulated iNOS expression and NO production. HNE selectively
      suppresses the former pathway, targeting a site downstream of Akt.

PMID- 11573245
TI  - Expression of different NF-kappaB pathway genes in dendritic cells (DCs) or
      macrophages assessed by gene expression profiling.
AB  - NF-kappaB/Rel transcription factors have been implicated in the differentiation
      of monocytes to either dendritic cells (DCs) or macrophages, as well as in the
      maturation of DCs from antigen-processing to antigen-presenting cells. Recent
      studies of the expression pattern of Rel proteins and their inhibitors (IkappaBs)
      suggest that their regulation during this differentiation process is
      transcriptional. To investigate differential gene expression between macrophages
      and DCs, we used commercially available gene microarrays (GEArray KIT), which
      included four of the NF-kappaB/Rel family genes (p50/p105, p52/p100, RelB, and c
      rel) and 32 additional genes either in the NF-kappaB signal transduction pathway
      or under transcriptional control of NF-kappaB/Rel factors. To generate
      macrophages and DCs, human adherent peripheral blood monocytes were cultured with
      M-CSF or GM-CSF + IL-4 respectively for up to 8 days. DCs (and in some
      experiments, macrophages) were treated with lipopolysaccharide (LPS) for the last
      48 h of culture to induce maturation. Cells were harvested after 7 days, cDNA was
      prepared and radiolabeled with alpha-(32)P-dCTP, then hybridized to gene arrays
      containing specific gene probes. beta-actin and GAPDH or PUC18 oligonucleotides
      served as positive or negative controls, respectively. The expression of all four
      NF-kappaB/Rel family genes examined was significantly upregulated in maturing DCs
      compared to macrophages. The strongest difference was observed for c-rel. RT-PCR
      determinations of c-rel, RelB, and p105 mRNAs confirmed these observations. Among
      the 32 NF-kappaB/Rel pathway genes, 14 were upregulated in mature DCs compared to
      macrophages. These genes were IkappaBalpha, IKK-beta, NIK, ICAM-1, P-selectin, E
      selectin, TNF-alpha, TNFR2, TNFAIP3, IL-1alpha, IL-1R1, IL-1R2, IRAK, and TANK.
      By contrast, only mcp-1 (monocyte chemotactic protein 1) was upregulated in
      macrophages compared to DCs. NF-kappaB pathway genes upregulated in DCs compared
      to macrophages were constitutively expressed in monocytes then selectively
      downregulated during macrophage but not DC differentiation. LPS did not induce
      expression of most of these genes in macrophages but LPS did induce upregulation
      of IL-8 in mature macrophages. We conclude that NF-kappaB/Rel family genes,
      especially c-rel, are selectively expressed during differentiation of monocytes
      towards DCs. Moreover, this differential expression is associated both with
      activation of different NF-kappaB signal transduction pathways in DCs and
      macrophages and with expression of a unique subset of genes in DCs that are
      transcriptionally targeted by NF-kappaB/Rel factors. The results illustrate the
      ability of the NF-kappaB pathway to respond to differentiation stimuli by
      activating in a cell-specific manner unique signalling pathways and subsets of NF
      kappaB target genes.

PMID- 11573246
TI  - Regulation of the subcellular distribution and gene expression of GABA(A)
      receptor by microtubules and microfilaments in cultured brain neurons.
AB  - Mechanisms underlying the intracellular transport of gamma-aminobutyric acid(A)
      receptor (GABA(A)R) were examined in the cultured neurons derived from chicken
      embryo brains. In situ trypsinization of the cultures and (3)H-flunitrazepam
      (FNZ) binding assay were employed to determine the cell surface and intracellular
      distribution of the receptor. A 3-h treatment of the cells with 1 microM of
      colchicine, a microtubule depolymerizer, reversibly raised the proportion of
      intracellular GABA(A)R density by about 36% and decreased that of the cell
      surface receptors by 18% from respective control values, whereas the 3-h
      incubation with 2 microM of cytochalasin D, a microfilament disrupter, did not
      cause significant changes. These treatments failed to alter the total number of
      the (3)H-FNZ binding sites of the neurons and the affinity of the ligand.
      Moreover, the exposure to colchicine seemed to produce a stronger cytoplasmic
      immunostaining of the GABA(A)R alpha subunits in many neurons without affecting
      the total cellular level of the proteins, in accordance with the increased
      fraction of intracellular (3)H-FNZ binding. However, in the neurons exposed to
      cytochalasin D, there was an increase of around 28% in the total content of
      alpha(1)+51kDa proteins. In addition, the colchicine or cytochalasin D treatment
      inhibited approximately 21 or 18% of the rate of general protein synthesis in the
      culture. Notably, in situ hybridization assay showed that the GABA(A)R alpha(1)
      or alpha(2) mRNA was present in 92 +/- 2% or 94 +/- 2% of the cytochalasin D
      treated neurons, both of which were higher than 71 +/- 2-74 +/- 3% of the control
      and colchicine-treated cells. The data suggest that by regulating the
      intracellular transport, the microtubular system participates in the maintenance
      of normal subcellular distribution of GABA(A)R in the neurons. By contrast, the
      organization of microfilaments may play a role in modulating the gene expression
      of GABA(A)R subunits.

PMID- 11573247
TI  - Critical amino acid residues of the alpha4 subunit for alpha4beta7 integrin
      function.
AB  - A characteristic feature of integrin-ligand interactions is the requirement for
      divalent cations. Putative cation binding sites have been identified in the alpha
      and beta subunit of the alpha4 integrins, alpha4beta1 and alpha4beta7, and within
      their ligands which display the tripeptide LDV in fibronectin and homologous
      motifs in VCAM-1 and MAdCAM-1. The extracellular domain of the murine and human
      alpha4-subunit contains three conserved LDV motifs, designated LDV-1 to -3. Using
      site directed mutagenesis and transfection studies, we now examined the
      functional relevance of the LDV motifs for alpha4beta7 integrins. We present
      evidence that LDV-1 mutants (D489N) behave like alpha4 wt cells, but LDV-3
      mutants (D811N) are impaired in alpha4beta7 integrin-triggered homotypic cell
      aggregation and in adhesion and spreading on alpha4 specific ligands. Further
      characterization of LDV-3 mutants revealed a defect in mAb-induced alpha4beta7
      cell surface cluster formation. Mutation of the LDV-2 motif (D698N) caused loss
      of alpha4beta7 integrin cell surface expression. Our results indicate: (i) that
      LDV-3, located proximal to the cell membrane, is important for alpha4beta7
      integrin-triggered functions and for lateral clustering and (ii) that LDV-2
      affects alpha4beta7 heterodimer stability.

PMID- 11573248
TI  - Regulation of osteoclastogenesis and RANK expression by TGF-beta1.
AB  - Transforming growth factor-beta (TGF-beta) has been shown to both inhibit and to
      stimulate bone resorption and osteoclastogenesis. This may be due, in part, to
      differential effects on bone marrow stromal cells that support osteoclastogenesis
      vs. direct effects on osteoclastic precursor cells. In the present study, we used
      the murine monocytic cell line, RAW 264.7, to define direct effects of TGF-beta
      on pre-osteoclastic cells. In the presence of macrophage-colony stimulating
      factor (M-CSF) (20 ng/ml) and receptor activator of NF-kappaB ligand (RANK-L) (50
      ng/ml), TGF-beta1 (0.01-5 ng/ml) dose-dependently stimulated (by up to 120-fold)
      osteoclast formation (assessed by the presence of tartrate-resistant acid
      phosphatase (TRAP) positive multinucleated cells and expression of calcitonin and
      vitronectin receptors). In addition, TGF-beta1 also increased steady state RANK
      mRNA levels in a time- (by up to 3.5-fold at 48 h) and dose-dependent manner (by
      up to 2.2-fold at 10 ng/ml). TGF-beta1 induction of RANK mRNA levels was present
      both in undifferentiated RAW cells as well as in cells that had been induced to
      differentiate into osteoclasts by a 7-day treatment with M-CSF and RANK-L. Using
      a fluorescence-labeled RANK-L probe, we also demonstrated by flow cytometry that
      TGF-beta1 resulted in a significant increase in the percentage of RANK+ RAW cells
      (P < 0.05), as well as an increase in the fluorescence intensity per cell (P <
      0.05), the latter consistent with an increase in RANK protein expression per
      cell. These data thus indicate that TGF-beta directly stimulates osteoclastic
      differentiation, and this is accompanied by increased RANK mRNA and protein
      expression.

PMID- 11573249
TI  - Utilization of a receptor reserve for effective amplification of mitogenic
      signaling by an epidermal growth factor mutant deficient in receptor activation.
AB  - The idea of a receptor reserve in mediating cellular function is well known but
      direct biochemical evidence has not been easy to obtain. This study stems from
      our results showing that L15 of epidermal growth factor (EGF) is important in
      both EGF receptor (EGFR) binding and activation, and the L15A analog of human EGF
      (hEGF) partially uncouples EGFR binding from EGFR activation (Nandagopal et al.,
      [1996] Protein Engng 9:781-788). We address the cellular mechanism of mitogenic
      signal amplification by EGFR tyrosine kinase in response to L15A hEGF. L15A is
      partially impaired in receptor dimerization, shown by chemical cross-linking and
      allosteric activation of EGFR in a substrate phosphorylation assay.
      Immunoprecipitation experiments reveal, however, that L15A can induce EGFR
      autophosphorylation in intact murine keratinocytes by utilizing spare receptors,
      the ratio of total phosphotyrosine content per receptor being significantly lower
      than that elicited by wild-type. This direct biochemical evidence, based on
      function, of utilization of a receptor reserve for kinase stimulation suggests
      that an EGF variant can activate varying receptor numbers to generate the same
      effective response. L15A-activated receptors can stimulate mitogen-activated
      protein kinase (MAPK) that is important for mitogenesis. The lack of linear
      correlation between levels of receptor dimerization, autophosphorylation, and
      MAPK activation suggests that signal amplification is mediated by cooperative
      effects. Flow cytometric analyses show that the percentages of cells which
      proliferate in response to 1 nM L15A and their rate of entry into S-phase are
      both decreased relative to 1 nM wild-type, indicating that MAPK activation alone
      is insufficient for maximal stimulation of mitogenesis. Higher concentrations of
      L15A reverse this effect, indicating that L15A and wild-type differ in the number
      of receptors each activates to induce the threshold response, which may be
      attained by cooperative activation of receptor dimers/oligomers by van der Waal's
      weak forces of attraction. The maintenance of a receptor reserve underscores an
      effective strategy in cell survival.

PMID- 11573251
TI  - Finessing the soft sell, ARO wraps a luminous New York City spa and boutique in
      seductively gossamer veils at QIORA.

PMID- 11573252
TI  - Digital pedagogy: an essay.

PMID- 11573253
TI  - [Refractory status of collagen diseases and diagnosis of complications: disease
      process during treatment and disease outcome].

PMID- 11573250
TI  - Participation of Survivin in mitotic and apoptotic activities of normal and tumor
      derived cells.
AB  - Survivin is a member of the inhibitor of apoptosis (IAP) gene family, containing
      a single baculovirus IAP repeat (BIR) and no RING finger, that is expressed in
      many human cancers. Although it has been proposed to be involved in mitotic and
      cytokinetic processes, its functional subcellular distribution in the cytoplasm
      and nucleus, and its binding to centrosomes, spindle fibers, and centromeres in
      relation to these processes, is not fully resolved. We have analyzed the
      localization of Survivin in normal (Detroit 551, IMR-90) and tumor-derived (HeLa,
      Saos-2) cell lines, and found that it does colocalize with centrosomes in the
      cytoplasm during interphase, then moves to centromeres during mitosis, and
      finally localizes to the midbody spindle fibers during telophase. However, Taxol,
      a popular microtubule stabilizing agent that is frequently used in the study of
      these processes, severely disrupted the localization of Survivin. Taxol treatment
      of cells promoted extensive relocalization of Survivin with alpha-tubulin on
      microtubules during either interphase or mitosis. Survivin antisense
      oligonucleotide markedly sensitized HeLa cells to cell death induced by agents
      acting at the level of cell surface receptor (Fas pathway) or at the level of
      mitochondria (etoposide). HeLa cell death induced by Survivin antisense
      oligonucleotide could be partially complemented by Deterin, the Drosophila
      homolog of Survivin (Jones et al. [2000] J. Biol. Chem. 275:22157-22166).
      Reciprocally, a chimera of the Deterin BIR domain and Survivin C-terminus could
      rescue Drosophila Kc cells from death induced by transfection of a human caspase
      7-expressing plasmid. These results indicate common components of Survivin and
      Deterin antiapoptotic action in the vertebrate and invertebrate phyla.

PMID- 11573254
TI  - [Alveolar hemorrhage].

PMID- 11573255
TI  - [Interstitial pneumonia].

PMID- 11573256
TI  - [Adult Still disease and ARDS].

PMID- 11573257
TI  - [Digestive system symptoms and peritonitis].

PMID- 11573258
TI  - [Pulmonary hypertension].

PMID- 11573259
TI  - [Anti-phospholipid antibody syndrome].

PMID- 11573260
TI  - [Thrombotic thrombocytopenic purpura].

PMID- 11573261
TI  - [Hemophagocytic syndrome].

PMID- 11573262
TI  - [Central nervous system lesions].

PMID- 11573263
TI  - [Lupus cystitis].

PMID- 11573264
TI  - [MPO-ANCA-related nephritis].

PMID- 11573265
TI  - [Kidney failure].

PMID- 11573266
TI  - [Steroid-resistant myositis].

PMID- 11573267
TI  - [Arthritis mutilans].

PMID- 11573268
TI  - [Retroperitoneal fibrosis].

PMID- 11573269
TI  - [Skin lesions and collagen diseases].

PMID- 11573270
TI  - [Refractory nature of collagen diseases: discussion].

PMID- 11573271
TI  - [Aldosterone-producing adenoma which was difficult to discriminate from
      idiopathic hyperaldosteronisim].

PMID- 11573272
TI  - [A patent foramen ovale accompanied with paradoxical cerebral embolism in a young
      patient].

PMID- 11573273
TI  - [Mixed connective tissue disease (MCTD) with severe acute pancreatitis].

PMID- 11573274
TI  - [Pheochromocytoma with severe paralytic ileus occurred from acute pulmonary edema
      caused by metoclopramide].

PMID- 11573275
TI  - [A rare case of primary adenoendocrine cell carcinoma of lower bile duct with
      anomalous creatine kinase isoenzyme and extremely high serum level of neuron
      specific enolase].

PMID- 11573276
TI  - [Critical illness polyneuropathy in mechanically ventilation with severe asthma].

PMID- 11573277
TI  - [Appropriate disinfection to prevent nosocomial infection].

PMID- 11573278
TI  - [Familial combined hyperlipidemia].

PMID- 11573279
TI  - [Overview of hepatitis C virus from its discovery to now].
AB  - Hepatitis C was first recognized as a form of viral hepatitis that was distinct
      from disease caused by hepatitis A virus and hepatitis B virus. The etiologic
      agent of hepatitis C was proposed to be a small, enveloped virus based on
      demonstrations of its transmissibility to chimpanzees, electron microscopic
      studies, and sensitive to chloroform. Successful molecular cloning of viral
      genome in the late 1980's led to the development of assay for serological
      diagnosis of HCV and it is currently estimated that at least 170 million people
      are chronically infected with the hepatitis C virus. HCV evades host antiviral
      defenses by mechanisms that remain to be identified and establishes a persistent
      infection in a majority of patients. Persistent infection of HCV is a leading
      cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma.
      Therefore development of antiviral treatment for HCV is an urgent worldwide
      health problem. Although much has been learned about HCV genome organization,
      polyprotein processing, protein function and structure, many key questions remain
      to be answered. Major efforts of Japanese investigators should now be directed at
      establishing cellular system and animal models appropriate for dissecting the
      various steps in HCV replication cycle and strategies for blocking them.

PMID- 11573280
TI  - [Past trends in hepatitis C virus infection and route of transmission in Japan].
AB  - In Japan, it is known that the prevalence of hepatitis C virus(HCV) is high among
      the older people over 60 years of age in sharp contrast to the low prevalence
      among those under 30. The annual incidence rate of HCV carriers in general
      population remains quite low to be 1.8-3.4 per 100,000 person-year. On the other
      hand, HCV prevalence among intravenous drug users(IVDU) is still greater than
      60%. Taking into account this epidemiological pattern together with the
      historical fact that Japan experienced an explosion of drug abuse among young
      generation of 15 to 25 years old in the period of post World War II turmoil
      together with the poor sanitary and medical conditions, it is suggested that a
      great wave of HCV spread in Japan occurred most likely in 1960's to 1970's. The
      spread then may have gradually fallen to the range today.

PMID- 11573281
TI  - [Future outlook for treatment of chronic hepatitis C: IFN + ribavirin combination
      therapy].
AB  - Japan has over 2 million patients infected with HCV and is currently facing a
      crisis of rapid increase in the number of patients with HCV-related liver
      cirrhosis and hepatocellular carcinoma. To overcome this situation, reliance is
      placed mainly on IFN therapy with the addition of various therapies to treat
      symptoms. The knowledge gained to date with IFN monotherapy and the expectations
      for efficacy to be achieved with IFN + ribavirin combination therapy have been
      presented.

PMID- 11573282
TI  - [Prognosis of chronic hepatitis C with regard to the aim of treatment].
AB  - Epidemiology of hepatitis C virus(HCV) infection and clinical prognosis of
      chronic hepatitis C were presented here to reveal the object of treatment of
      Chronic Hepatitis C. Hepatitis C Virus is transmitted by blood and blood
      products. After acute HCV infection, about 70% developed persistent HCV
      infection, and the diagnosis is by finding viral RNA in the serum of patients
      with anti-HCV antibody. Persistent HCV infection causes chronic hepatitis, in
      which the natural clearance of HCV is almost impossible and there is almost no
      natural cure for chronic hepatitis caused by HCV. Chronic hepatitis C tends to
      develop gradually and to progress to liver cirrhosis, and is involved in the
      pathogenesis of hepatocellular carcinoma. In Japanese patients with chronic
      hepatitis C, 45% developed liver cirrhosis pass through a phase of chronic active
      hepatitis over a 15-year course after initial HCV infection, and 25% developed
      hepatocellular carcinoma over a 20-year course after the initial HCV infection.
      In addition the remaining patients may start to develop rapidly to chronic active
      hepatitis and to liver cirrhosis after 20 to 30 years duration of inactive phase.
      Thus, this type of chronic hepatitis reveals a poor long-term prognosis. For
      etiological treatment of chronic hepatitis C, eradication of persistent HCV
      infection is needed. If this is impossible, then preventing the development of
      liver cirrhosis and hepatocellular carcinoma is important.

PMID- 11573283
TI  - [HCV infection in medical environments].
AB  - Since the discovery of the hepatitis C virus(HCV), it has become evident that
      this infectious agent is a primary cause of posttransfusion and sporadic non-A,
      non-B hepatitis. Populations at risk for HCV infection include health care
      workers, infants born to HCV-infected mothers, hemodyalysis patients, and
      intravenous drug abusers. Because there currently is no HCV vaccine or specific
      immunoglobulin against HCV, prevention of exposure remains the only possibility
      for reducing HCV transmission and prevalence. However, the percentage of
      individuals who are positive for HCV antibody among health care workers is not
      significantly high, suggesting that health care workers are not at very high risk
      of HCV infection. Too much fear of HCV infection among the health care workers
      should be avoided.

PMID- 11573284
TI  - [The examinations associating with hepatitis C virus and medical reimbursement].
AB  - The number of persons infected with hepatitis C virus(HCV) is estimated to be
      about one to two million in Japan. Recently researchers have shown a growing
      interest in HCV, since the virus infection may cause liver cirrhosis and
      hepatocellular carcinoma. The examinations for HCV can be divided into host
      factor and virus factor detection methods. Classification and cost of HCV tests
      are shown. Antibody tests as host factor detection are used to screen for
      infection, for auxiliary diagnosis of viremia and for choosing treatment. Virus
      factor tests, such as the measurement of the viral load can be used for choosing
      treatment and determining the response to therapy. We describe that usage of
      laboratory tests for HCV and discuss medical insurance coverage.

PMID- 11573285
TI  - [Human herpes virus and malignancies].
AB  - Two type of human herpes viruses, type 4(Epstein Barr virus, EBV) and type
      8(HHV8) are known to cause malignancies. Among those, EBV is the very most
      popular human oncovirus. It can cause malignant lymphomas of various subtypes
      including Burkitt's lymphoma, opportunistic lymphomas, pyothorax-associated
      lymphoma, nasal T/NK cell lymphoma, Hodgkin's disease and a part of diffuse large
      cell lymphomas. HHV8 is a new member of human oncovirus associating with primary
      effusion lymphoma, a part of solid lymphoma taking diffuse large or anaplastic
      large cell morphology, and the Castleman's tumor. Introduction of histopathologic
      methodologies makes the correct diagnosis of those herpes virus-associated tumors
      an easy routine test.

PMID- 11573286
TI  - [Cellular origin of human B-cell neoplasms and Hodgkin's disease based on
      analysis of somatic hypermutations in the immunoglobulin variable region genes].
AB  - In response to antigen stimulation, B cells undergo a germinal center(GC)
      reaction such as somatic hypermutations of the immunoglobulin variable region
      genes, which results in the production and selection of antigen-specific
      antibodies with increased affinity. Therefore, somatic hypermutations are
      considered to be a hallmark of GC B cells and their descendants. Pre-GC B
      cells(precursor B cells, immature B cells, naive B cells and CD5+ B cells) carry
      no somatic hypermutations, whereas GC B cells and post-GC B cells(memory B cells
      and plasma cells) express somatic hypermutations. This phenomenon is useful in
      identifying the cellular origin of various B-cell neoplasms. Precursor B
      lymphoblastic leukemia/lymphoma, mantle cell lymphoma, and most B-CLL originate
      from pre-GC B cells, and follicular lymphoma, Burkitt's lymphoma, marginal zone B
      cell lymphoma, diffuse large B-cell lymphoma and myeloma from GC B cells or post
      GC B cells. Nodular lymphocyte-predominant Hodgkin's disease and most classical
      types of Hodgkin's disease are derived from GC B cells. Most human-B cell
      neoplasms including Hodgkin's disease are derived from GC B cells or their
      descendants. Molecular processes that modify the DNA of GC B cells, such as
      somatic hypermutation, class switching and receptor editing occur in the
      environment of the GCs, and increase the risk of malignant transformation.

PMID- 11573287
TI  - [Importance of a network construction with each division and clinical laboratory
      in the hospital--from a ground of the infection control nurse].
AB  - To reduce the frequency and extent hospital infection, the infection prevention
      team is required to work properly. Infection control nurses play various roles in
      the infection prevention team, including surveillance of the occurrence of
      infection and checking the actual conditions of infection prevention activities,
      as well as the communication and coordination with other sections. Thus, they
      take part in almost all the activities of the infection prevention team, except
      the diagnosis and the medical treatment of infectious diseases; that is to say,
      they make reports, communicate, consult and cooperate with the staff members of
      other sections. As for surveillance, the results of microbiological tests by a
      laboratory are most important. By feedback regarding the results of surveillance
      measures against infection, infection prevention activities become more
      effective. The staff members of the microbiological laboratory and the infection
      control nurses can obtain information about the outbreak of infection at an early
      stage, which is critical in infection prevention activities. Therefore, good
      cooperation between nurses and the laboratory staff facilitates prompt and
      appropriate actions to prevent further spread of infection. The test section,
      especially the microbiological laboratory, is the most important section with
      which the infection control nurses should work in close cooperation.

PMID- 11573288
TI  - [In terms of infection control team(ICT)].
AB  - We think it is important to make up a medical team for the infection control in
      the hospital since patients admitted often turn to compromised hosts who
      possessed the high risk to provoke the possible transmission of nosocomial
      infections. Infection control team(ICT) under the infection control
      committee(ICC) was established in our Yamagata University Hospital at the 1994
      April. Members of the ICT are composed of staffs at various sections: physicians,
      pharmacists, nurses, clinical laboratory staffs, a neutrionist and administration
      office staffs, with the aim of preventing the nosocomial infections. Twenty three
      staffs of ICT who are specialist at each section have practiced the round of
      wards, leading in hand-washing, checking of the proper use of antibiotics and
      disinfectants, making and revising of the infection control manual, follow-up of
      the route of infection, and a countermeasure of prevention for needle pad
      accidents, etc. Furthermore, ICT has exerted all possible efforts of various
      investigations for infections when it is necessary. Problems that are faced our
      ICT are the construction of a network an inter-net among clinical divisions,
      nursing, pharmacy and clinical laboratory, and a system of the centralized
      management is actualized thereby.

PMID- 11573289
TI  - [Hospital infection control in 21st century, the importance of networking with
      each division and clinical laboratory in the hospital. 1. From the aspect of
      clinical laboratory division].
AB  - Clinical laboratory division plays an important roll for the management of
      nosocomial infection. Staff from clinical laboratory division including
      technologist and/or medical doctor can work as a part of infection control team.
      Since the bacterial surveillance data from clinically isolated strains
      accumulates in the clinical laboratory division, these staff have a chance to
      notice outbreak in hospital at first time. While handling information from each
      strain, we need to feedback these data with additional information for
      physicians. From June, 2000, a national project started. That was a surveillance
      program for drag-resistant bacteria. We can compare information from local
      isolates and nation-wide isolates by this project. Genotypic methods especially
      pulsed-field gel electrophoresis(PFGE) is suitable for the identification of
      infection route in the hospital environment. And PFGE analysis for pathogenic
      strains works effective in our hospital.

PMID- 11573290
TI  - [Hospital infection control in the 21st century--importance of network for
      hospital infection control and role of clinical laboratory].
AB  - The clinical laboratory is important as a department which provides diagnostic
      and advisory services to clinicians and support surveillance for hospital
      infection control. Though the link between clinical laboratory and other
      departments including infection control team is paramount for infection control,
      there are the communication delays by the documented reports. The use of the
      hospital information system can streamline the work of infection control, because
      laboratory(including microbiology) data can be obtained quickly. In order to
      implement efficient infection control, it is necessary to construct the
      information network by utilizing the local area network in the hospital. Since
      the community-acquired infections due to resistant micro-organisms are increasing
      in 1990s, we should expand the information network in community and nation-wide
      in the 21st century.

PMID- 11573291
TI  - [Laboratory system for networks in infection control].
AB  - The goals of a surveillance for nosocomial infections are to observe the
      magnitude and characteristics of the infections, and to plan and evaluate
      policies and guidelines of infection control. In clinical laboratory, although it
      is most important to detect their causative pathogens, further to provide the
      surveillance study as a multicenter. Actually, we have just started an infection
      control room in our hospital. Thus this room may present various informations
      about infection and contribute to the networks with the area community.

PMID- 11573292
TI  - Urinary 17-hydroxycorticosteroids and 17-ketosteroid sulfates in normal children
      and in children with atopic dermatitis or renal disease.
AB  - We measured both urinary 17-hydroxycorticosteroids(17-OHCS) and 17-ketosteroid
      sulfates(17-KS-S) in normal children and in children with some diseases to
      evaluate adaptation to stress in children. 17-OHCS and 17-KS-S values were
      measured in morning urine from 60 normal children(3-18 years old) and 24 children
      with atopic dermatitis or renal disease. In normal children, the 17
      OHCS/creatinine showed no difference by age, but both 17-KS-S/creatinine and 17
      KS-S/17-OHCS showed significant positive correlation with age. No sex differences
      were significant. In children with atopic dermatitis or with renal disease
      treated with cyclosporine A, 17-OHCS/creatinine was significantly higher and the
      17-KS-S/17-OHCS ratio was significantly lower than in age-matched controls. These
      values returned to normal as the conditions improved or as treatment ended. In
      patients who underwent renal biopsy, both 17-OHCS/creatinine and 17-KS
      S/creatinine values were significantly higher after biopsy than before because of
      the stress caused by pain and complete bed rest. Measurement of urinary 17-OHCS
      and 17-KS-S in children can be useful for evaluation of adaptation to stress as
      well as in adults.

PMID- 11573293
TI  - [Plasma levels of soluble fibrin in patients with disseminated intravascular
      coagulation].
AB  - Soluble fibrin(SF) is formed in the early-activated state of blood coagulation
      and quantitative measurement of SF shows high potential as a parameter for the
      diagnosis of suspected disseminated intravascular coagulation(DIC). The aim of
      the present study is to evaluate the usefulness of a newly developed SF test
      utilizing SF specific monoclonal antibody(F405). Among hemopoietic and non
      hemopoietic tumor patients, 249 patients with suspected DIC were collected. The
      SF level showed a good correlation with the DIC score and the SF levels in DIC
      patients were significantly higher than those in s-DIC and pre-DIC patients.
      Receiver operating characteristic(ROC) analysis also showed that the specificity
      and sensitivity of the SF assay were higher than those of thrombin-antithrombin
      complex(TAT). In conclusion, these results indicate that the SF assay is a highly
      precise method for the diagnosis and screening of DIC stages.

PMID- 11573294
TI  - [Present status and future aspects of studies in Alzheimer disease].

PMID- 11573296
TI  - [Outcome research of patients with schizophrenia].

PMID- 11573295
TI  - [Efficacy of atypical antipsychotic agents for maintenance therapy of
      schizophrenia].

PMID- 11573297
TI  - [The psychopathology of severe obsessive-compulsive disorder: Zwangskrankheit and
      primary obsessional slowness].
AB  - In investigation obsessive-compulsive phenomena, it is important to not only
      regard them as a kind of symptomatology extending across a variety of diagnostic
      categories on the basis of faint similarities of symptoms from the cross
      sectional point of view, but also to take into account how the psychopathology of
      a nuclear form of severe obsessive-compulsive disorder (OCD) is different from a
      neurotic form from the vertical-sectional point of view. In this paper, the
      psychopathological features of 3 cases of Zwangskrankheit and primary obsessional
      slowness, which are considered to be nuclear forms of severe OCD, are reported.
      We suggest that 'obsessive-compulsive pseudophobia' lies behind Zwangskrankheit,
      and 'obsessive-compulsive depersonalization' lies behind primary obsessional
      slowness. In both disorders, a peculiar form of avoidance behavior, called
      'pathological access to safety signal' was observed in which dangerous situations
      were avoided by taking no other action other than a determined one. Thus never
      making a mistake was stressed in their actions which is a feature of adherence to
      extra-orderliness. Therefore, a patient with Zwangskrankheit lives a restricted
      life according to strict rules characteristic of ritualization of one's whole
      life, while a patient with primary obsessional slowness acts according to the
      principle of miticulousness. Thus we considered that this kind of avoidance
      behavior is the result of a loss of safety signal not by the existence of a
      danger signal. In a neurotic form of OCD, patients may attempt to superficially
      restore the safety signal by avoiding the danger signal. In comparing the
      psychopathology of OCD with agoraphobia, avoidance behavior involves space in the
      latter, while it is an act in the former. Obsessive-compulsive pseudophobia and
      obsessive-compulsive depersonalization are hypothesized to be the background of
      symptoms of a neurotic form of OCD, but since the patients do not experience them
      as phenomena and so cannot take them into the field of consciousness, then they
      are likely to feel them, literally 'obsessive-compulsive.'

PMID- 11573298
TI  - A publishing odyssey: what medical librarian authors and journal purchasers need
      to know.

PMID- 11573299
TI  - A method for collecting Web page usage statistics.

PMID- 11573300
TI  - OPL. Practical tips for the solo practitioner.

PMID- 11573301
TI  - Inspiring patrons to use Loansome Doc. A simple approach to getting started.

PMID- 11573302
TI  - An inch of performance is worth a mile of cure.

PMID- 11573303
TI  - Solving equipment conundrums.

PMID- 11573304
TI  - Buying time. Deadline for class III devices extended.

PMID- 11573305
TI  - A gown for all occasions.

PMID- 11573306
TI  - Multidrug-resistant tuberculosis.

PMID- 11573307
TI  - Health insurance.

PMID- 11573308
TI  - Current treatment of hepatobiliary malignancies.
AB  - In summary, it should be noted that patients with underlying chronic liver
      disease such as viral hepatitis have many alternatives for therapy, including
      resection and transplantation. It is imperative that these patients receive early
      referral to a center with experience in performing liver resections and the
      ability to perform hepatic transplantation.

PMID- 11573309
TI  - Sir William Osler's continued appeal to learn signs and symptoms of disease (a
      message to the graduating class of 2001, School of Medicine, University of
      Louisville).

PMID- 11573310
TI  - Professionalism.

PMID- 11573311
TI  - "That there child has a green gall upon its liver".

PMID- 11573312
TI  - Women in medicine--2001: my perspective.

PMID- 11573313
TI  - Medicine in the Postgenome Era.

PMID- 11573314
TI  - Surgical battery and informed consent.

PMID- 11573315
TI  - Ventricular septal defect in the 9th decade.
AB  - This case reports the oldest patient with a large, unoperated, isolated,
      congenital ventricular septal defect in the literature. Issues related to the
      natural history of the disease and its management are discussed.

PMID- 11573316
TI  - Today's health crisis: a laughing matter?

PMID- 11573318
TI  - The role of accreditation in medical education.

PMID- 11573317
TI  - Box jellyfish (Carybdea alata) in Waikiki. The analgesic effect of sting-aid,
      Adolph's meat tenderizer and fresh water on their stings: a double-blinded,
      randomized, placebo-controlled clinical trial.
AB  - The study measured the analgesic effects of three popular Hawaii remedies for
      stings from the box jellyfish, Carybdea alata. Analysis of data showed that
      aerosol sprays of Sting-Aid (an aluminum sulfate solution), Aldolph's meat
      tenderizer dissolved in water, and fresh water neither increased nor decreased
      the pain of box jellyfish stings more than the control (seawater).

PMID- 11573319
TI  - [Monitoring of uropathogens and their susceptibility to antibiotics].
AB  - Samples of urine collected from patients with complicated urology infection and
      hospitalized to the Moscow Region Research Clinical Institute in 1986, 1991, 1995
      and 1999 were analysed. Of 11,444 samples examined, bacteriuria was estimated in
      7143 samples. 9786 strains (29 genus) of bacteria were isolated--56.9 per cent as
      mono culture and 43.1 per cent as associations. Susceptibility to 21 antibiotic
      was determined by disk diffusion method for 1607 strains; beta-lactamase
      production was determined in 198 strains, MIC was determined for 41 antibiotics.
      Gram-negative rods relative amount among pathogens decreased substantially (84.7
      per cent in 1986 against 61.6 per cent in 1999), particularly Enterobacteriaceae
      (74.7 per cent in 1986 against 41.4 per cent in 1999). Nonfermenting Gram
      negative rods (NFGNR) relative amount increased (10.8 per cent against 19.2 per
      cent), along with Gram-positive cocci (19.8 per cent against 64.2 per cent),
      particularly coagulasenegative staphylococci (CNS) (10.8 per cent against 35.9
      per cent) and enterococci (5 per cent against 16.5 per cent) and candida and
      fungi (0.5 per cent in 1986 against 15.9 per cent in 1999). At the period 1986
      1999 the main pathogens in urology infection were E. coli, Enterobacter spp.,
      NFGNR (including P. aeruginosa), Staphylococcus, CNS, Enterococcus spp. The
      problem pathogens for urological department were the following: E. coli,
      Klebsiella spp., Enterobacter spp., Proteus spp., NFGNR including P. aeruginosa,
      CNS, Enterococcus spp., candida and fungi. At the period 1991-1997 Gram-negative
      pathogens susceptibility to amikacin, ofloxacin, ciprofloxacin, imipenem,
      ceftazidime, cefotaxime was not changed in general, Gram-positive cocci
      (staphylococci and enterococci) retained the same susceptibility to vancomicin,
      cefamandol and amoxyclave. Staphylococci were also susceptible to amikacin,
      imipenem, rifampicin, oxacillin, ciprofloxacin, and ofloxacin. Production of beta
      lactamase was registered for 38.7 per cent of CNS, 26.5 per cent of E. coli, 38.5
      per cent of K. pneumoniae, 25 per cent of P. mirabilis and 55.6 per cent of P.
      aeruginosa strains.

PMID- 11573320
TI  - [Clinical significance of infection pathogen resistance in a urological clinic
      for selection of antibacterial therapy regimes for the treatment of complicated
      urinary infections].
AB  - Data on changes of etiological structure of the complicated urinary tract
      infections treated at the Research Institute of Urology and Hospital No. 47 at
      the 5-year period (1996-2000) are given. It was shown that the most important
      microorganisms were the following: Enterobacter spp., E. coli, Proteus spp.,
      Staphylococcus spp., Enterococcus faecalis. The correlation between frequency of
      the microorganisms isolation and their susceptibility to antimicrobial agents at
      different periods was analysed. The results of analysis allowed to elaborate
      algorithm of etiotropic therapy. Choice of the drug depends on pathogen
      susceptibility to antibiotics, bacteriuria level and clinical symptoms severity.

PMID- 11573321
TI  - [Candidosis of the central nervous system in children of the first year--one of
      the problems in nosocomial fungal infections].
AB  - CNS candidosis is a severe disease, one of the nosocomial fungal infections, with
      often lethal issue or invalidation of the patient. Specific signs are absent and
      early diagnosis is very difficult. Risk factors are the following: prematurity,
      candidal carriage, prolonged hospitalization, treatment with broad spectrum
      antibiotics and immunosupressors, artificial pulmonary ventilation. No single
      effective antifungal agent exists. In the case of acute fungal CNS infection the
      drug of choice is fluconazole (diflucan) characterized by high efficacy and CSF
      sanitation rate, the drug is used intravenously with possible switching off to
      oral form. If the pathogen is not susceptible to the drug (C. crusel, C. glabrata
      and C. tropicalis) amphotericin B is recommended (C. lusitaniae is not
      susceptible). In the case of renal or hepatic failure AmBisome may be used as
      less toxic form. If the case of prolonged disease antifungal drugs are used in a
      long-term regime, drugs combinations are also recommended. Complex therapy with
      granulocyte colony stimulating factor may be used if the previous regime was not
      effective.

PMID- 11573323
TI  - [Atypical pneumonia].

PMID- 11573322
TI  - [Resistance to glycopeptide antibiotics. New horizons and problems].

PMID- 11573324
TI  - [A new generation of fluoroquinolones--new possibilities for the treatment of
      respiratory community-acquired infections].

PMID- 11573326
TI  - Smooth sailing for physicians and health plans?

PMID- 11573325
TI  - [Severe community-acquired pneumonia: etiology].
AB  - A complex microbiological (sputum, protected brush biopsy of the bronchial
      mucosa) and immunological examination of 40 male patients (the average age of
      55.4 +/- 8.8 years) with severe community-acquired pneumonia (risk classes III-V
      according to Fine M.J. et al., 1997) revealed the disease etiology in 52.5 per
      cent of the cases. The leading pathogen was Streptococcus pneumoniae. It was
      detected in 61.6 per cent of the cases of the etiologically verified pneumonia.
      Staphylococcus aureus and Klebsiella pneumoniae were also among the actual
      pathogens (14.3 and 14.3 per cent respectively). The Legionnaires infection was
      not confirmed in any of the patients (enzyme-linked immunological analysis of
      urine for the serotype 1-6 Legionella pneumophila antigen). In the absolute
      majority of the patients the isolated pneumococci were susceptible (E-test) to
      benzylpenicillin. Only in 1 patients with severe pneumonia and secondary
      bacteriemia the pneumococcal isolates were moderately resistant to
      benzylpenicillin (the MIC of 0.125 mg/ml). Still, they were susceptible to
      ceftriaxone (the MIC of 0.023 mg/ml). The data are useful in the development of a
      national (regional) programme for empirical antibacterial therapy of severe
      community-acquired pneumonia.

PMID- 11573327
TI  - Turning the tide of increasing medical malpractice premiums.

PMID- 11573328
TI  - The results are in. 2001 MD data survey on practice characteristics: Part I.

PMID- 11573332
TI  - Leadership savvy: helping others find increased meaning and satisfaction in the
      practice of medicine.

PMID- 11573333
TI  - The fight goes on. 20 years of the AIDS epidemic.

PMID- 11573334
TI  - My short (but wide) list of state priorities.

PMID- 11573335
TI  - A selective overview of issues on classification, causation, and early intensive
      behavioral intervention for autism.
AB  - Autism is a behaviorally defined disorder that comprises a controversial
      diagnostic category due to heterogeneity in symptomatology, causation, and
      etiology and significant variance in response to intervention. In this article,
      the authors provide a brief overview of the clinical category and a summary of
      diagnostic developments with respect to the American Psychiatric Association's
      Diagnostic and Statistical Manual of Mental Disorders. Regarding causation and
      etiology, they briefly discuss selected perspectives from the fields of cognitive
      neuroscience and neuropsychology. The article concludes with a summary of
      effective behavioral strategies for the treatment of children with autism. This
      section highlights the importance of early intensive behavioral intervention and
      includes a discussion of some important aspects of this approach.

PMID- 11573336
TI  - The benefits of Skinner's analysis of verbal behavior for children with autism.
AB  - Behavior analysis has already contributed substantially to the treatment of
      children with autism, and further gains can result from more use of Skinner's
      analysis of language in Verbal Behavior (1957) and in the resulting conceptual
      and experimental work. The approach emphasizes a unit of analysis consisting of
      the relations between behavior, motivative and discriminative variables, and
      consequences. Skinner identifies seven types of verbal operants--echoic, mand,
      tact, intraverbal, textual, transcriptive, and copying a text--which function as
      components of more advanced forms of language. This approach focuses on the
      development of each verbal operant (rather than on words and their meanings) and
      on the independent training of speaker and listener repertoires. Five more
      specific contributions are described that relate to the importance of (a) an
      effective language assessment, (b) mand training in early intervention, (c)
      establishing operations, (d) an intraverbal repertoire, and (e) automatic
      reinforcement.

PMID- 11573337
TI  - The Picture Exchange Communication System.
AB  - The Picture Exchange Communication System (PECS) is an alternative/augmentative
      communication system that was developed to teach functional communication to
      children with limited speech. The approach is unique in that it teaches children
      to initiate communicative interactions within a social framework. This article
      describes the advantages to implementing PECS over traditional approaches. The
      PECS training protocol is described wherein children are taught to exchange a
      single picture for a desired item and eventually to construct picture-based
      sentences and use a variety of attributes in their requests. The relationship of
      PECS's implementation to the development of speech in previously nonvocal
      students is reviewed.

PMID- 11573338
TI  - Identifying early intervention targets for children with autism in inclusive
      school settings.
AB  - This study assessed play and social behavior of young children with autism in
      inclusive school settings to identify important targets for intervention. Data
      were collected for five children with autism and for typically developing peers.
      All children with autism received intervention in one-on-one settings but did not
      have individual education plan goals that provided systematic intervention for
      developing play and social skills in their school settings. Results indicated the
      children with autism and their typically developing peers played with a
      comparable number of stimulus items (e.g., toys), but the children with autism
      engaged in these activities for shorter durations. Both children with autism and
      their typically developing peers engaged in similar levels of social interaction
      with adults. However, the children with autism rarely or never engaged in social
      interactions with their peers, whereas the typically developing peers frequently
      engaged in social interactions with other children. The results suggest important
      targets for intervention.

PMID- 11573339
TI  - Including children with autism in general education classrooms. A review of
      effective strategies.
AB  - Children with autism can benefit from participation in inclusive classroom
      environments, and many experts assert that inclusion is a civil right and is
      responsible for nurturing appropriate social development. However, most children
      with autism require specialized supports to experience success in these
      educational contexts. This article provides a review of the empirical research
      that has addressed procedures for promoting successful inclusion of students with
      autism. Strategies reviewed include antecedent manipulations, delayed
      contingencies, self-management, peer-mediated interventions, and other approaches
      that have been demonstrated in the literature to be useful. The article concludes
      with a discussion of future research needs.

PMID- 11573341
TI  - Protein folding and its links with human disease.
AB  - The ability of proteins to fold to their functional states following synthesis in
      the intracellular environment is one of the most remarkable features of biology.
      Substantial progress has recently been made towards understanding the fundamental
      nature of the mechanism of the folding process. This understanding has been
      achieved through the development and concerted application of a variety of novel
      experimental and theoretical approaches to this complex problem. The emerging
      view of folding is that it is a stochastic process, but one biased by the fact
      that native-like interactions between residues are, on average, more stable than
      non-native ones. The sequences of natural proteins have emerged through
      evolutionary processes such that their unique native states can be found very
      efficiently even in the complex environment inside a living cell. But under some
      conditions proteins fail to fold correctly, or to remain correctly folded, in
      living systems, and this failure can result in a wide range of diseases. One
      group of diseases, known as amyloidoses, which includes Alzheimer's disease and
      the transmissible spongiform encephalopathies, involves deposition of aggregated
      proteins in a variety of tissues. These diseases are particularly intriguing
      because evidence is accumulating that the formation of the highly organized
      amyloid aggregates is a generic property of polypeptides, and not simply a
      feature of the few proteins associated with recognized pathological conditions.
      That such aggregates are not normally found in properly functional biological
      systems is again a testament to evolution, in this case of a variety of
      mechanisms inhibiting their formation. Understanding the nature of such
      protective mechanisms is a crucial step in the development of strategies to
      prevent and treat these debilitating diseases.

PMID- 11573340
TI  - Teaching social skills to people with autism.
AB  - The treatment of social skills deficits remains one of the most challenging areas
      in meeting the needs of people with autism. Difficulties in understanding social
      stimuli, in initiating and responding to social bids, and in appreciating the
      affect that is intrinsic to social interactions can be baffling for people with
      autism. Researchers and practitioners of applied behavior analysis have tried a
      variety of strategies for teaching social skills. This article examines a range
      of useful procedures for teaching social skills to people with autism, including
      skills that are adult mediated, peer mediated, and child-with-autism mediated.
      The authors also consider the potential of classwide interventions in inclusive
      settings, pivotal response training, and the use of scripts to teach social
      initiations.

PMID- 11573342
TI  - Guidelines for the assembly of novel coiled-coil structures: alpha-sheets and
      alpha-cylinders.
AB  - The coiled coil is a ubiquitous motif that guides many different protein-protein
      interactions. The accepted hallmark of coiled coils is a seven-residue (heptad)
      sequence repeat. The positions of this repeat are labelled a-b-c-d-e-f-g, with
      residues at a and d tending to be hydrophobic. Such sequences form amphipathic
      alpha-helices, which assemble into helical bundles via knobs-into-holes
      interdigitation of residues from neighbouring helices. We wrote an algorithm,
      SOCKET, to identify this packing in protein structures, and used this to gather a
      database of coiled-coil structures from the Protein Data Bank. Surprisingly, in
      addition to commonly accepted structures with a single, contiguous heptad repeat,
      we identified sequences with multiple, offset heptad repeats. These 'new'
      sequence patterns help to explain oligomer-state specification in coiled coils.
      Here we focus on the structural consequences for sequences with two heptad
      repeats offset by two residues, i.e. a/f'-b/g'-c/a'-d/b'-e/c'-f/d'-g/e'. This
      sets up two hydrophobic seams on opposite sides of the helix formed. We describe
      how such helices may combine to bury these hydrophobic surfaces in two different
      ways and form two distinct structures: open 'alpha-sheets' and closed 'alpha
      cylinders'. We highlight these with descriptions of natural structures and
      outline possibilities for protein design.

PMID- 11573343
TI  - Protease inhibitors and directed evolution: enhancing plant resistance to
      nematodes.
AB  - Plant nematodes are agricultural pests, the control of which relies on chemical
      nematicides and fumigants that are among the most toxic and environmentally
      damaging of all agrochemicals. New approaches to control, based on transgenic
      resistance, would provide important health and environmental benefits. In this
      chapter we consider briefly some targets for engineering nematode resistance and
      discuss the use of plant protease inhibitors as anti-feedants. This approach has
      provided plants that display good levels of resistance against a range of
      nematode species. To enhance this defence strategy further we are investigating
      the value of directed evolution to improve the characteristics of protease
      inhibitors. We describe the approaches of DNA shuffling and phage display that
      are being used to create and screen variant libraries in the search for
      inhibitors with improved features.

PMID- 11573344
TI  - Degradation of explosives by nitrate ester reductases.
AB  - Explosive-contaminated land poses a hazard both to the environment and to human
      health. Microbial enzymes, either in their native or heterologous hosts, are a
      powerful and low-cost tool for eliminating this environmental hazard. As many
      explosives have only been present in the environment for 10 years, and with
      similar molecules not known in Nature, the origin of enzymes specialized for the
      breakdown of explosives is of particular interest. Screening of environmental
      isolates resulted in the discovery of flavoproteins capable of denitrating the
      explosives pentaerythritol tetranitrate (PETN) and glycerol trinitrate. These
      nitrate ester reductases are related in sequence and structure to Old Yellow
      Enzyme from Saccharomyces carlsbergenisis. All the members of this family have
      alpha/beta barrel structures and FMN as a prosthetic group, and reduce various
      electrophilic substrates. The nitrate ester reductases are, however, unusual in
      that they display activity towards the highly recalcitrant, aromatic explosive
      2,4,6-trinitrotoluene, via a reductive pathway resulting in nitrogen liberation.
      We have embarked on a detailed study of the structure and mechanism of PETN
      reductase from a strain of Enterobacter cloacae. Work is focused currently on
      relating structure and function within this growing family of enzymes, with a
      view to engineering novel enzymes exhibiting useful characteristics.

PMID- 11573345
TI  - Manipulating the folding of membrane proteins: using the bilayer to our
      advantage.
AB  - The folding mechanisms of integral membrane proteins have largely eluded detailed
      study. This is owing to the inherent difficulties in folding these hydrophobic
      proteins in vitro, which, in turn, reflects the often apparently insurmountable
      problem of mimicking the natural membrane bilayer with lipid or detergent
      mixtures. There is, however, a large body of information on lipid properties and,
      in particular, on phosphatidylcholine and phosphatidylethanolamine lipids, which
      are common to many biological membranes. We have exploited this knowledge to
      develop efficient in vitro lipid-bilayer folding systems for the membrane
      protein, bacteriorhodopsin. Furthermore, we have shown that a rate-limiting
      apoprotein folding step and the overall folding efficiency appear to be
      controlled by particular properties of the lipid bilayer. The properties of
      interest are the stored curvature elastic energy within the bilayer, and the
      lateral pressure that the lipid chains exert on the their neighbouring folding
      proteins. These are generic properties of the bilayer that can be achieved with
      simple mixtures of biological lipids, and are not specific to the lipids studied
      here. These bilayer properties also seem to be important in modulating the
      function of several membrane proteins, as well as the function of membranes in
      vivo. Thus, it seems likely that careful manipulations of lipid properties will
      shed light on the forces that drive membrane protein folding, and will aid the
      development of bilayer folding systems for other membrane proteins.

PMID- 11573346
TI  - Self-perpetuating changes in Sup35 protein conformation as a mechanism of
      heredity in yeast.
AB  - Recently, a novel mode of inheritance has been described in the yeast
      Saccharomyces cerevisiae. The mechanism is based on the prion hypothesis, which
      posits that self-perpetuating changes in the conformation of single protein, PrP,
      underlie the severe neurodegeneration associated with the transmissible
      spongiform enchephalopathies in mammals. In yeast, two prions, [URE3] and [PSI+],
      have been identified, but these factors confer unique phenotypes rather than
      disease to the organism. In each case, the prion-associated phenotype has been
      linked to alternative conformations of the Ure2 and Sup35 proteins. Remarkably,
      Ure2 and Sup35 proteins existing in the alternative conformations have the unique
      capacity to transmit this physical state to the newly synthesized protein in
      vivo. Thus, a mechanism exists to ensure replication of the conformational
      information that underlies protein-only inheritance. We have characterized the
      mechanism by which Sup35 conformational information is replicated in vitro. The
      assembly of amyloid fibres by a region of Sup35 encompassing the N-terminal 254
      amino acids faithfully recapitulates the in vivo propagation of [PSI+]. Mutations
      that alter [PSI+] inheritance in vivo change the kinetics of amyloid assembly in
      vitro in a complementary fashion, and lysates from [PSI+] cells, but not [psi-]
      cells, accelerate assembly in vitro. Using this system we propose a mechanism by
      which the alternative conformation of Sup35 is adopted by an unstructured
      oilgomeric intermediate at the time of assembly.

PMID- 11573347
TI  - Contribution of molecular chaperones to protein folding in the cytoplasm of
      prokaryotic and eukaryotic cells.
AB  - While it is clear that many unfolded proteins can attain their native state
      spontaneously in vitro, the efficiency of such folding is usually limited to
      conditions far removed from those encountered within cells. Two properties of the
      cellular environment are expected to enhance strongly the propensity of
      incompletely folded polypeptides to misfold and aggregate: the crowding effect
      caused by the high concentration of macromolecules, and the close proximity of
      nascent polypeptide chains emerging from polyribosomes. However, in the living
      cell, non-productive protein folding is in many, if not most, cases prevented by
      the action of a highly conserved set of proteins termed molecular chaperones. In
      the cytoplasm, the Hsp70 (heat-shock protein of 70 kDa) and chaperonin families
      of molecular chaperones appear to be the major contributors to efficient protein
      folding during both normal conditions and adverse conditions such as heat stress.
      Hsp70 chaperones recognize and shield short, hydrophobic peptide segments in the
      context of non-native polypeptides and probably promote folding by decreasing the
      concentration of aggregation-prone intermediates. In contrast, the chaperonins
      interact with and globally enclose collapsed folding intermediates in a central
      cavity where efficient folding can proceed in a protected environment. For a
      number of proteins, folding requires the co-ordinated action of both of these
      molecular chaperones.

PMID- 11573348
TI  - Defining the structure of the substrate-free state of the DnaK molecular
      chaperone.
AB  - Members of the Hsp70 (heat-shock protein of 70 kDa) family of molecular
      chaperones bind to exposed hydrophobic stretches on substrate proteins in order
      to dissociate molecular complexes and prevent aggregation in the cell. Substrate
      affinity for the C-terminal domain of the Hsp70 is regulated by ATP binding to
      the N-terminal domain utilizing an allosteric mechanism. Our multi-dimensional
      NMR studies of a substrate-binding domain fragment (amino acids 387-552) from an
      Escherichia coli Hsp70, DnaK(387-552), have uncovered a pH-dependent
      conformational change, which we propose to be relevant for the full-length
      protein also. At pH 7, the C-terminus of DnaK(387-552) mimics substrate by
      binding to its own substrate-binding site, as has been observed previously for
      truncated Hsp70 constructs. At pH 5, the C-terminus is released from the binding
      site, such that DnaK is in the substrate-free state 10-20% of the time. We
      propose that the mechanism for the release of the tail is a loss of affinity for
      substrate at low pH. The pH-dependent fluorescence changes at a tryptophan
      residue near the substrate-binding pocket in full-length DnaK lead us to extend
      these conclusions to the full-length DnaK as well. In the context of the DnaK
      substrate-binding domain fragment, the release of the C-terminus from the
      substrate-binding site provides our first glimpse of the empty conformation of an
      Hsp70 substrate-binding domain containing a portion of the helical subdomain.

PMID- 11573349
TI  - Validation of protein-unfolding transition states identified in molecular
      dynamics simulations.
AB  - Experimental and simulation studies can complement each other nicely in the area
      of protein folding. Experiment reports on the average properties of a large
      ensemble (approx. 10(17)-10(19) molecules), typically over time. Molecular
      dynamics simulations, on the other hand, provide detailed information for a
      single molecule, a component of the ensemble. By combining these approaches we
      can obtain not only a more complete picture of folding, but we can also take
      advantage of the strengths of different methods. For example, experiment cannot
      provide molecular structures. Molecular dynamics simulations can provide such
      information, but the simulations are meaningless without a linked experiment.
      Thus, the interrelated nature of simulation in assessing experimental assumptions
      and in providing structures to augment energetic descriptions, and experiment in
      judging whether the simulations are reasonable, provides more confidence in the
      resulting information about folding. This combination yields tested and testable
      molecular models of states that evade characterization by conventional methods.
      Therefore, we have explored the combined use of these methods to map
      folding/unfolding pathways at atomic resolution, in collaboration with Alan
      Fersht. Here we focus on chymotrypsin inhibitor 2, a small single-domain, two
      state folding protein.

PMID- 11573350
TI  - Structure, stability and folding of the alpha-helix.
AB  - Pauling first described the alpha-helix nearly 50 years ago, yet new features of
      its structure continue to be discovered, using peptide model systems, site
      directed mutagenesis, advances in theory, the expansion of the Protein Data Bank
      and new experimental techniques. Helical peptides in solution form a vast number
      of structures, including fully helical, fully coiled and partly helical. To
      interpret peptide results quantitatively it is essential to use a helix/coil
      model that includes the stabilities of all these conformations. Our models now
      include terms for helix interiors, capping, side-chain interactions, N-termini
      and 3(10)-helices. The first three amino acids in a helix (N1, N2 and N3) and the
      preceding N-cap are unique, as their amide NH groups do not participate in
      backbone hydrogen bonding. We surveyed their structures in proteins and measured
      their amino acid preferences. The results are predominantly rationalized by
      hydrogen bonding to the free NH groups. Stabilizing side-chain-side-chain
      energies, including hydrophobic interactions, hydrogen bonding and polar/non
      polar interactions, were measured accurately in helical peptides. Helices in
      proteins show a preference for having approximately an integral number of turns
      so that their N- and C-caps lie on the same side. There are also strong periodic
      trends in the likelihood of terminating a helix with a Schellman or alpha L C-cap
      motif. The kinetics of alpha-helix folding have been studied with stopped-flow
      deep ultraviolet circular dichroism using synchrotron radiation as the light
      source; this gives a far superior signal-to-noise ratio than a conventional
      instrument. We find that poly(Glu), poly(Lys) and alanine-based peptides fold in
      milliseconds, with longer peptides showing a transient overshoot in helix
      content.

PMID- 11573351
TI  - More money, less available. Insurance premiums' double-digit rise is no surprise
      to hospitals.

PMID- 11573352
TI  - A good crop. For-profits find ground for growth in a landscape of Catholic
      systems.

PMID- 11573353
TI  - Bad reputation. HMOs' image takes another hit in poll.

PMID- 11573354
TI  - Together at last. Ochsner clinic and hospital in New Orleans officially one
      organization.

PMID- 11573355
TI  - AMA forges ahead. Unveiling of educational campaign paid by drug industry
      triggers new criticism.

PMID- 11573356
TI  - The lobby was too quiet. Providers' failure to speak out against the tax cut may
      be very costly.

PMID- 11573357
TI  - That giant whirring sound you hear is either an artificial heart or Louisville's
      Jewish Hospital cashing in on being first.
AB  - For Jewish Hospital in Louisville, Ky., a modest-looking device made of titanium
      and plastic could be the ticket to healthcare's big leagues. Earlier this summer
      the hospital was the first to implant the AbioCor artificial heart, and it's been
      riding a wave of media acclaim ever since. Hospital President Doug Shaw hopes the
      facility can cash in on its successes.

PMID- 11573358
TI  - Healthcare donations surge. But slumping economy, HIPAA regulations pose
      challenges for fund-raisers.

PMID- 11573359
TI  - Where's the money? As lawmakers debate who lost the surplus, providers hold out
      hands.

PMID- 11573360
TI  - AHA votes against error tracking.

PMID- 11573361
TI  - Vigilance pays off for HMOs. NCQA finds health plans can identify and manage
      major diseases.

PMID- 11573362
TI  - CMA sues state. Opposes release of med groups' finance information.

PMID- 11573363
TI  - Africa. Hustling for corpses.

PMID- 11573364
TI  - Alzheimer's. A dignity in dementia.

PMID- 11573365
TI  - About cocaine and bananas.

PMID- 11573366
TI  - Pumping it up.

PMID- 11573367
TI  - Sponsorship, authorship, and accountability.

PMID- 11573368
TI  - [Drug therapy of functional dyspepsia. A review based on Cochrane Reviews].

PMID- 11573369
TI  - [Dyspepsia. Investigation and treatment].
AB  - Dyspepsia is defined as chronic or recurrent pain or discomfort centred in the
      upper abdomen. Early satiety, nausea, vomiting, or bloating are often also
      present. Dyspepsia should be differentiated from gastro-oesophageal reflux
      disease, whose predominant symptoms are heartburn and acid regurgitation.
      Prevalence rates vary between 25% and 40%, and dyspepsia is the main reason for
      consulting GPs: 3-5% of all visits. Older patients and patients presenting with
      alarm symptoms (weight loss, anaemia, jaundice, dysphagia, bleeding) should
      undergo endoscopy, but apart from this no other management strategy has been
      agreed upon. Management strategies based on non-invasive H. pylori testing will
      probably prove cost-effective and safe. However, the results of clinical trials
      are awaited before guidelines can be offered. The symptomatic effects of treating
      patients with functional dyspepsia with either acid inhibitors, prokinetics, or
      H. pylori eradication therapy are difficult to predict and are usually quite
      modest.

PMID- 11573370
TI  - [Back pain].

PMID- 11573371
TI  - [Are obesity and overweight risk factors of asthma?].
AB  - It has recently been suggested that overweight and obesity could be possible risk
      factors for asthma. A review of clinical and epidemiological studies of children
      and adults shows that a significant association between a high body mass index
      (BMI) and asthma can often be found. Yet, at present, we think that it is too
      early to conclude that overweight and obesity should be regarded as established
      risk factors for asthma. In particular, there is a need for more longitudinal
      studies to confirm the association between asthma and overweight and to shed
      light on which condition develops first. In addition, there is also a need for
      clinical studies of possible biological mechanisms that could link these two
      common conditions.

PMID- 11573372
TI  - [Gallbladder polyps].
AB  - Polyps in the gall bladder are detected in 4-5% of the population and most of
      them are benign. However, they can be premalignant and the prognosis for gall
      bladder carcinoma is still poor. As with other cancers, treatment at an early
      stage is therefore, considered essential to improve the prognosis. Because of the
      very low morbidity after laparoscopic cholecystectomy we recommend laparoscopic
      cholecystectomy when a polyp in the gall bladder is detected by ultrasonography.
      A wait and see attitude with repeated ultrasonography twice a year may be chosen,
      if there are contra-indications to laparoscopic cholecystectomy. If the lesion
      increases in size, cholecystectomy should be performed.

PMID- 11573373
TI  - [Cryopreservation of human ovarian tissue. Method of freezing and therapeutic
      use].
AB  - The medical treatment of various cancers may, as long-term sequelae, cause
      infertility in girls and young women. In order to preserve the fertility of such
      women, techniques to cryopreserve ovarian tissue have gained considerable
      interest during recent years. The ovarian tissue is cryopreserved before cancer
      treatment is commenced, and first replaced when the woman has been cured. Based
      on the successful results from the use of this technique in test animals, where
      normal live young have been born, cryopreservation of human ovarian tissue has
      been initiated in a number of fertility clinics worldwide over the last few
      years. So far, only two women have experienced transplantation of cryopreserved
      ovarian tissue. Menstrual cycles and oestradiol production were restored in both
      women, but restoration of fertility have not yet been demonstrated. This review
      describes the technique and its present possibilities and limitations. The legal
      aspects in Denmark are presented and some ethical aspects described.

PMID- 11573374
TI  - [New therapeutic perspectives in breast ductal carcinoma in situ].
AB  - Management of ductal carcinoma in situ (DCIS) of the breast has suffered from a
      lack of consensus. The results of recent studies may create the basis for a more
      rational treatment strategy. Surgical treatment of DCIS with mastectomy is
      curative, but often unnecessary. Excision, in contrast, carries a recurrence risk
      of 10-63%, and the recurrence is invasive in half the patients. Two large studies
      have shown that irradiation after breast conservation reduces the recurrence risk
      to almost half. Thus, adjuvant radiotherapy should, in principle, be offered.
      Retrospective analyses indicate, however, that patients having tumours removed
      with a > 10 mm free margin or with small, low-grade tumours may be considered to
      be adequately treated by surgery alone. A recent study showed that adjuvant
      antihormone therapy further reduces the risk of recurrence. The absolute benefit
      seems low, however, and additional investigations are required.

PMID- 11573375
TI  - [Psychological intervention during pregnancy. A multidisciplinary hospital
      network].
AB  - INTRODUCTION: Pregnancy and the puerperium are vulnerable periods in every
      woman's life. It is important to catch and treat signs of mental distress so as
      to prepare the woman for her approaching delivery, to optimize her role as a
      mother, and to prevent development of severe psychopathology. We describe a
      professional network (midwife, obstetrician, psychologist, and child
      psychiatrist) at a Danish county hospital, which offers the pregnant woman
      psychological therapy and/or psychiatric treatment when needed. MATERIAL AND
      METHODS: The study includes a retrospective analysis of 106 consecutive referrals
      from the department of obstetrics to the department of psychiatry in the period
      1994-1999. The variables were frequency and reason for referral, the diagnostic
      profile according to ICD-10, the number of therapeutic sessions, and registration
      of pregnancy/birth complications (PBC). RESULTS AND DISCUSSION: Anxiety and
      crisis reactions owing to previous PBC, family problems, and concerns about the
      fetus were the predominant reasons for referral. A total of 87% met the ICD-10
      criteria for adjustment disorder (F 43.2), whereas psychotic disorders were
      infrequent. In 52%, 1-4 sessions were sufficient to stabilise the condition. The
      frequency of PBC in the 106 women was significantly higher when compared to the
      background sample (n = about 15,000). The establishment of an effective network
      is recommended for pregnant women suffering from mental distress in order to
      prepare her for the approaching delivery, to optimise her forthcoming role as a
      mother, and to prevent development of severe psychopathology.

PMID- 11573376
TI  - [Risk of hemorrhage after outpatient versus inpatient tonsillectomy].
AB  - INTRODUCTION: This study evaluates the risk of post-tonsillectomy haemorrhage in
      outpatient surgery compared to conventional inpatient management. MATERIAL AND
      METHODS: We reviewed 528 tonsillectomies performed at the ENT Department,
      Rigshospitalet, University of Copenhagen, in the period 1.6.1997 to 31.5.1998.
      The 264 outpatient tonsillectomies were compared with 264 inpatient procedures.
      The number of post-operative haemorrhages and the time interval from operation to
      post-operative bleeding were registered, along with the need for re-operation.
      Outpatients were discharged 8 hours after surgery, inpatients after 24 hours.
      RESULTS: Forty-five (8.5%) of 528 tonsillectomies had post-operative haemorrhage
      complications, 15 (2.8%) patients needed a re-operation. Twenty-five (55%) cases
      of reactionary haemorrhage occurred < 8 hours after surgery and nine needed a re
      operation. Two of three cases of post-operative haemorrhage 8-24 hours after
      primary surgery were re-operated, whereas four of 17 patients with haemorrhage >
      24 hours post-operatively needed another surgery. There were no differences
      between inpatient and outpatient management. Eighty-nine per cent of all early (0
      24 h) post-operative haemorrhages occurred < 8 hours post-operatively. In the
      time period from 8-24 hours post-operatively there were only three cases of
      reactionary haemorrhage. The risk of post-operative haemorrhage after discharge
      was 4.2% and 3.4% after outpatient and inpatient management respectively, a
      difference of only 0.8%. This makes outpatient tonsillectomy an acceptable
      alternative to inpatient management.

PMID- 11573377
TI  - [Histological examination of the gallbladder after cholecystectomy].
AB  - BACKGROUND AND OBJECTIVES: Normally, the gallbladder is sent routinely for
      histological examination after cholecystectomy. From a cost-benefit point of view
      this may not be optimal. METHODS: Computerised records were used to identify
      patients with gallbladder carcinoma over a 20-year period, from 1979 to 1999, and
      these patient records were evaluated manually. RESULTS: The estimated cost for
      one histological examination was $37. During the period, 4,614 cholecystectomies
      were performed and 33 patients had gallbladder carcinoma. In 29 of the 33
      patients, there was evident preoperative and/or peroperative suspicion of cancer,
      but no such suspicion in four patients. These four patients had other
      peroperative macroscopic abnormal findings, besides gallbladder stones.
      CONCLUSION: This retrospective series indicates that in the case of normal
      preoperative and/or peroperative macroscopic conditions (except for gallbladder
      stones) there is no need for histological examination of the gallbladder.

PMID- 11573378
TI  - [Gender differences of post-traumatic headache and other post-commotio symptoms.
      A follow-up study after a period of 9-12 months].
AB  - BACKGROUND AND AIM: Symptoms following head injury are common. The aim of the
      present study was to estimate the association between age, sex, unconsciousness
      in connection with the trauma, type of accident, headache before the trauma,
      fractures, and post-traumatic headache, or other symptoms. MATERIALS AND METHODS:
      The patients studied were aged 18-60 years and had been under observation at the
      University Hospital of Aarhus in the period August 1986 to August 1987, because
      of concussion or suspected concussion. The records were examined, and the
      patients were interviewed by telephone 9-12 months after the trauma. RESULTS: Out
      of 233 patients, 168 were interviewed (72%). Of these, 57% had symptoms and 26%
      had received treatment. Two per cent were still on sick leave. Sixty-four
      patients (38%) complained of post-traumatic headache, whereas 31% had symptoms
      without post-traumatic headache, most often difficulties with memory or
      concentration. In a logistic regression model we estimated the adjusted odds
      ratio of having post-traumatic headache in women compared with men to 2.6 (1.2
      5.8), whereas the corresponding OR for other symptoms was 1.0 (0.4-2.7).
      CONCLUSION: We found that women had an increased risk of post-traumatic headache,
      but not other post-traumatic symptoms, in comparison with men.

PMID- 11573379
TI  - [Optimal interval screening and observation of abdominal aortic aneurysms].
AB  - INTRODUCTION: Screening and observation of abdominal aortic aneurysms (AAA)
      produce psychological stress. Consequently, safe and optimal intervals of
      rescreening and observation must be developed. METHOD: In a randomised, mass
      screening trial of 6,339 men aged, 65-73 years from 1994 to 1998, 76% attended,
      and 191 (4%) had AAA > or = 3 cm. Twenty-four (0.5%) had AAA above 5 cm in
      diameter and were referred for surgery, while the rest were offered annual
      control. Later, all 348 (7.5%) men who, 3 to 5 years before, had had an ectatic
      aorta (an infrarenal aortic diameter of 25-29 mm or a distal/renal aortic
      diameter ratio of > 1.2) were offered rescreening, together with a control group
      of 380 men. RESULTS: None of the controls had developed AAA. Of those who
      initially had an aortic diameter of 25-29 mm aorta, 28.5% had developed AAA (size
      range 30-48 mm), whereas only 3.5% with a ratio > 1.2 developed AAA (size range
      30-34 mm). During the fourth year of surveillance some AAA initially sized below
      3.5 cm expanded to above 5 cm, whereas this occurred in some sized 3.5-3.9 cm
      during the second year and in most above 4 cm did during the first year of
      observation. CONCLUSION: Rescreening for AAA can be restricted to initially
      ectatic aortas sized 25-29 mm at five-year intervals. Observation of small AAA
      can be restricted to 1-4 year intervals.

PMID- 11573380
TI  - [Isolated purulent arthritis of lumbar facet joint].
AB  - We present the case of a 51-year-old woman suffering from septic arthritis of a
      lumbar facet joint, which was probably caused by an infected central venous
      catheter. Increased uptake on the bone scintigraphy was an early finding.
      Magnetic resonance imaging (MRI) of the spine contributed to the diagnosis by
      showing lesions of the facet joint and involvement of the surrounding soft
      tissues. Percutaneous needle aspiration guided by computed tomography established
      a bacteriological diagnosis. The positive response to antibiotic therapy was
      confirmed by MRI.

PMID- 11573381
TI  - [RTH syndrome--resistance to thyroid hormone syndrome].
AB  - The RTH syndrome is an instructive example of a receptor resistance syndrome. A
      typical case history is reported here. The patient had had symptoms for many
      years and was first diagnosed as having inappropriate secretion of TSH. Pituitary
      tumour was excluded. The primary symptom was palpitations and the patient was
      partially thyroidectomized many years ago on suspicion of thyrotoxicosis. She was
      then given substitutional Eltroxin, but, because of palpitations, the dose was
      reduced to almost zero, after which the patient contracted symptoms suggesting
      myxoedema. The thyroid values could not be used for clinical assessment, however
      the symptoms of myxoedema disappeared when the Eltroxin dose was increased to 75
      micrograms/day. When the dose was increased further the heart symptoms became too
      troublesome. The patient had no signs of underlying heart disease.

PMID- 11573382
TI  - [Picture of the month: echinococcosis].

PMID- 11573383
TI  - [Mononucleosis--diagnosis and treatment].

PMID- 11573384
TI  - [Mononucleosis--diagnosis and treatment].

PMID- 11573385
TI  - [X-ray images in the past and now].

PMID- 11573386
TI  - [An open dialogue about Roskilde Festival 2000].

PMID- 11573387
TI  - Insurance hassles: don't get mad, get results.

PMID- 11573388
TI  - Stop the money drain!

PMID- 11573389
TI  - Scoop up every dollar you've earned.

PMID- 11573390
TI  - Physician liability and drug recalls.

PMID- 11573391
TI  - The painkiller prescription: protect use, prevent abuse.

PMID- 11573392
TI  - Will managed care die in court?

PMID- 11573393
TI  - Don't call me a primary care physician!

PMID- 11573394
TI  - When you need a second legal opinion.

PMID- 11573395
TI  - E-mail patients? Don't be nervous. Do be careful.

PMID- 11573396
TI  - Fighting the "pickle" in my head.

PMID- 11573397
TI  - [Clinical blood analysis with estimation of subpopulations of lymphocytes and
      possible mistakes of interpretation].

PMID- 11573398
TI  - [Problem of normal values and pathology in medicine].

PMID- 11573399
TI  - [Adaptative changes in immunograms in healthy children, living in zones of higher
      radiation].

PMID- 11573400
TI  - [Activation of immune system in acute inflammatory diseases].

PMID- 11573401
TI  - [Can changes in immune and cytological status always be considered
      pathological?].

PMID- 11573402
TI  - [EEG-biomanagement method in the treatment of attention deficit and hyperactivity
      disorders].

PMID- 11573403
TI  - [Change in the heart rate during exam stress in people born in different months].

PMID- 11573404
TI  - [Influence of the season of birth date on individual character, health, emotional
      stress for adolescents].

PMID- 11573405
TI  - [One more time about fine structure of alpha-rhythm EEG in humans: two spectral
      components in the resting condition].

PMID- 11573406
TI  - [Brain mechanisms of free regulation of activity and the beginning of writing
      skills for seven- to eight-year-old children].

PMID- 11573407
TI  - [Differences in topographic organization of EEG depends on temporal traits].

PMID- 11573408
TI  - [Brain and heart: The problem of the wave field of man].

PMID- 11573409
TI  - [Variations in cardiac rhythm during different problem solving tasks].

PMID- 11573410
TI  - [Age and sex differences in reaction time for moving objects in children and
      adults].

PMID- 11573411
TI  - [Research of brain organization of the creative process. Part III. Brain
      activation according to data from analysis of local brain blood circulation and
      EEG].

PMID- 11573412
TI  - [Significance of spectral-time parameters of noise during forced exhalation in
      the estimation of bronchi airways].

PMID- 11573413
TI  - [Estimation of anaerobic thresholds based on heart rate changes during standard
      exercise].

PMID- 11573414
TI  - [Effective coughing depends on physical characteristics of parenchyma and
      airways].

PMID- 11573415
TI  - [Localization of tremor generator].

PMID- 11573416
TI  - [Hemorheological status of an organism with normal versus changed blood vessels].

PMID- 11573417
TI  - [Physiological-morphological differences in the formation of thyroid status in
      Aboriginal and migrant populations of the Magadan province].

PMID- 11573418
TI  - [Dynamics of blood plasma levels of follicle stimulating hormone, luteinizing
      hormone, prolactin, estradiol and progesterone of right handed and left handed
      women].

PMID- 11573420
TI  - [Role of apoptosis in age-related pathologies].
AB  - A review of recent data concerning the apoptotic death of cells during senescence
      at the organismic level. The data analyzed suggest interrelations between
      apoptosis deregulation and some age-related pathologies and senescent phenotypes.
      Genetic aspects and possible mechanisms of age-related changes in the program of
      apoptosis are considered. It has been proposed that age-related deregulation of
      apoptosis is a mechanism of senescence.

PMID- 11573419
TI  - [Typical immune system responses to differential monotherapy with immune
      correcting drugs].

PMID- 11573421
TI  - [Variations in the size of mitotic cells in the root meristem].
AB  - Variations in the length of mitotic and interphase cells were analyzed in various
      tissues of wheat roots and in the cortex of maize roots. Reliable differences
      were shown in the length of mitotic cells in individual files-clones of cells of
      the same tissue. The mean lengths of dividing cells in different roots differed
      to a lesser extent than those of different files in the same tissue of one root.
      Within the file, the length of sister simultaneously dividing cells differed the
      least, while the difference of lengths of neighbor simultaneously dividing
      nonsister cells was bigger. The mean length of interphase cells in any file was
      always less than that of mitotic cells by a factor of 1.45. This ratio was almost
      invariable for files and tissues in both plants we studied and corresponded to
      that of an exponentially growing cell population. In addition, a very small
      number of cells were found (less than 1%) in meristems, which are longer than the
      mitotic cells. The length of these cells exceeded those of mitotic cells by less
      than twice. The origin of such cells is discussed. The length of mitotic cells
      near the quiescent center is more variable than in the middle of the meristem in
      the cortex of both plants. In the meristem basal part, the mitotic cells were no
      longer than those in the middle of the meristem but there were no small dividing
      cells. In the wheat epidermis, the cells are differentiated into trichoblasts and
      atrichoblasts and, therefore, the length of dividing cells is highly variable.
      The cell length is essential for their transition to mitosis for all studied
      proliferating meristem cells.

PMID- 11573422
TI  - [Use of biometric characteristics of major salivary glands as a base line to
      develop a formula for the quantitative estimation of posttraumatic regeneration
      of glandular tissue].
AB  - In experiments conducted on 903 rats, we have studied biometric characteristics
      of the major salivary glands (parotid, submandibular, and sublingual glands)
      during ontogenesis. We have calculated the indices of non-directional fluctuation
      asymmetry for the submandibular and sublingual glands and determined correlation
      coefficients and coefficients of linear regression between salivary glands, rat
      body weight, and the weight of the femoral bone (the largest bone in the rat).
      The strongest correlation was found between the dry weight of the submandibular
      gland and the rat body weight. Mathematical analysis of the growth of the
      submandibular gland after sialotomy allowed us to derive a formula for the
      quantitative estimation of regeneration, taking into account the natural growth
      of the rat.

PMID- 11573424
TI  - [Sex-related differences in blood and gonad levels of testosterone in silver fox
      fetuses].
AB  - The mass of silver fox fetuses of both sexes, their gonads, and adrenals, and the
      levels of testosterone in blood serum and in gonads and adrenals were determined
      from day 31 of gestation and every five days thereafter until its termination.
      Marked sex-related differences were revealed: the blood and gonad levels of
      testosterone in male fetuses were much higher than those in female fetuses. The
      fetal adrenals contained significantly less testosterone than the gonads. No sex
      related differences in the content of testosterone in the fetal adrenals were
      found. No differences were found in the body and adrenal mass in female and male
      fetuses at all the developmental stages studied, while the mass of ovaries
      exceeded that of testes from day 45 of gestation. The data obtained suggest sex
      dimorphism in the production of testosterone by gonads in silver foxes appears
      after day 35 and appears to correspond to the period of morphological
      differentiation of gonads.

PMID- 11573423
TI  - [A study of the complex of proteolytic enzymes and their protein inhibitors in
      embryogenesis of the silkworm].
AB  - We studied changes in the activities of serin, thiol, and aspartyl proteinases
      and their protein inhibitors during embryogenesis of the silkworm. The dynamics
      of activities of the protein inhibitors and specific proteinases were
      interrelated, thus providing for coordination and fine regulation of functioning
      of the proteolytic complex of enzymes during embryogenesis. Possible functions of
      peptidohydrolases and their protein inhibitors in the silkworm are discussed.

PMID- 11573425
TI  - [Fertilization and subsequent development of cattle oocytes after reduced
      incubation with spermatozoa].
AB  - We studied the influence of the duration of joint incubation of cattle oocytes
      and spermatozoa (18 versus 1 h) on fertilization, cleavage, and embryonic
      development in vitro until the blastocyst stage. Spermatozoa of a bull of the
      Britanofrizskaya breed were used in the experiments. It was shown in the first
      experimental series that after a long-term incubation with the spermatozoa, the
      percentage of penetrated eggs increased: 71.7% and 56.0% (p < 0.05) after 18-hour
      and 1-hour incubation, respectively. However, no differences were found in the
      number of normally fertilized eggs: 46.5 and 39.0%, respectively. In the second
      experimental series, no significant differences were found in either the number
      of cleaving embryos (41.2 and 32.2%, respectively) or the capacity of cleaving
      embryos to develop in vitro until the blastocyst stage (21.7 and 15.8%,
      respectively). Thus, reduction in the time of joint incubation of cattle gametes
      upon in vitro fertilization to 1 h did not reduce the number of normally
      fertilized eggs and did not affect their capacity for subsequent in vitro
      development.

PMID- 11573426
TI  - [Artificially applied tensions normalize development of relaxed Xenopus Laevis
      embryos].
AB  - Relaxation of tensions of the surface of Xenopus laevis embryos at the late
      blastula stage leads to deep and diverse developmental defects and increased
      variability in mutual position and volume ratios of the axial rudiments. Here, we
      demonstrate that the development of such embryos was markedly normalized if the
      relaxed tensions were restored in one of two ways: (1) isotropic stretching of
      the blastocoel roof induced by incubation of relaxed embryos in a hypotonic
      medium or (2) anisotropic stretching of embryos on two needles. In the latter
      case, we succeeded in restoring the morphological axis not only after
      longitudinal stretching, but also after transverse stretching, and the new axis
      had signs of anteroposterior polarity. The role of isotropic and anisotropic
      tensions in organization of the early amphibian development is discussed.

PMID- 11573427
TI  - [Relationship between the induction of MDR1, a multidrug resistance gene in tumor
      cells, and apoptosis].
AB  - Gene MDR1 coding for P-glycoprotein belongs to a group of genes responsible for
      cell defense. Overexpression of this gene determines the resistance of tumor
      cells to a series of chemotherapeutic drugs known as multidrug resistance. Many
      chemotherapeuticals induce both apoptosis and transcriptional activity of the
      MDR1 gene in tumor cells. It is not known, however, how these two processes are
      associated with each other. In order to elucidate a possible link between them,
      we have studied the sphyngomyelinic pathway of signal transduction. This pathway
      is activated in response to various stress factors and includes the hydrolysis of
      sphyngomyelin of cytoplasmic membrane resulting in an accumulation of
      intracellular ceramide, which activates cascades of enzymatic reactions leading
      to various cell responses, including apoptosis. C2 ceramide (N-acetyl-D
      sphyngosine) and cytosar (1 beta-D-arabinosylcytosine, or ara C) were used to
      induce the sphyngomyelinic pathway. Their effects on human hemoblastosis cell
      lines (K562 and H9 cell lines) were examined. C2 ceramide and ara C induced
      apoptosis in both cell lines over an 18-h incubation. C2 ceramide also induced an
      increase in the expression of the gene MDR1 in both cell lines, while ara C
      increased the activity of the gene MDR1 only in H9 cells. The results obtained
      provide evidence for the contribution of ceramide-mediated signal pathway to the
      control of MDR1 activity.

PMID- 11573428
TI  - [Activity of embryonic mink genome during diapause (cytogenetic analysis):
      nucleolar and extranucleolar rna synthesis].
AB  - The nucleolar and extranucleolar RNA synthesis was studied in the mink
      blastocysts at different stages of embryonic diapause and during the
      periimplantation period using cytoradioautography. The data obtained suggest a
      differential and stage specific activity of the embryonic mRNA and rRNA synthesis
      during the period of delayed implantation.

PMID- 11573429
TI  - [Study of the transfer of foreign genes into mussel Mytilus Galloprovincialis
      Lam. eggs by spermatozoa].
AB  - The possibility of transferring exogenous DNA into eggs by mussel Mytilus
      galloprovincialis Lam. sperms both with the use of certain methods of
      transfection and without them was studied. The efficacy of egg fertilization by
      sperms treated with foreign DNA and the development of larvae at early stages of
      embryogenesis were evaluated. Negative effects of the contact between mussel
      sperms and exogenous DNA on fertilization and subsequent development were noted.
      The proportion of developing larvae decreased with increasing DNA concentration
      and sperm exposure. Transfer of plasmids pCMVlacZ and pMTbGH into eggs was
      observed in group crosses. With the use of PCR, foreign DNA sequences were found
      in the larvae at the stage of veliger 48 h after fertilization. An intense signal
      was recorded after sperm electroporation in 10% DMSO.

PMID- 11573430
TI  - Leapfrog is no threat.

PMID- 11573432
TI  - Standards could save lives.

PMID- 11573433
TI  - Another tech 'must'.

PMID- 11573434
TI  - RN staffing is key.

PMID- 11573435
TI  - Finance. We'll be watching you.

PMID- 11573436
TI  - Insurance. Who am I?

PMID- 11573439
TI  - Managed care. Change afoot.

PMID- 11573440
TI  - Technology at what price?

PMID- 11573441
TI  - Information technology. Sharing is caring.

PMID- 11573442
TI  - 1Q[3a]. Do newspaper birth notices lead to infant abductions?

PMID- 11573443
TI  - What if?

PMID- 11573444
TI  - Paper slammed.
AB  - Health & Human Services Secretary Tommy Thompson and others in Washington say
      that they are serious about easing the confusing and costly regulations that
      burden the health care field. It's a promise hospital executives have heard many
      times before. Is there any reason to believe that this time real help is finally
      on the horizon?

PMID- 11573445
TI  - Sharing the IT pain.
AB  - Outsourcing info tech is too appealing a temptation for many hospitals to pass
      up. Information technology is costly, complex, prone to breakdowns and ever
      changing. Many hospitals already outsource part of their IT operation, but there
      appears to be a trend toward outsourcing entire departments. Recently, a number
      of deals worth hundreds of millions of dollars were announced by some of the
      nation's largest systems and outsourcing companies. While outsourcing is the best
      alternative for certain operations, for others it may just be a trade-off between
      a short-term headache and long-term pain.

PMID- 11573446
TI  - ASPs: the lure of task outsourcing.

PMID- 11573447
TI  - More than money.

PMID- 11573448
TI  - [Diabetes mellitus as a general membrane disease and its consequences].
AB  - The metabolic disturbances and their consequences in diabetes mellitus are well
      known more or less in details too. However, our knowledge on the diabetic
      disorders in membrane functions are limited. These damages are connected mostly
      with the disregulation of the membrane protein syntheses due to deficiency of
      insulin. In this review the impairments of the Na(+)-pump and the Ca(2+)
      transport mechanisms as well as the insulin-dependent glucose transporter GLUT4
      will be discussed in diabetes. The capacity of these transporters could be
      decreased even more than 50 percent in diabetes. This is the reason why using the
      same dose of cardioactive steroids as if in not diabetic subjects--can cause
      toxic alterations on the heart in diabetic patients. Insulin regulates not only
      the expression of some membrane proteins but it can initiate the translocation of
      the Na(+)-pump and GLUT4 from the intracellular membrane compartments to the
      plasma membrane in muscle, heart and adipose tissue. Therefore the uptake of K+
      and glucose into these tissues will increase significantly under the acute
      influence of insulin. Untreated diabetic patients generally show hyperkalemia.
      Forceful treatment with insulin of these subjects often causes severe hypokalemia
      as a consequence of sudden translocation of the Na(+)-pump. Different Ca(2+)
      transport systems are also impaired in diabetes. These changes may result
      significantly higher free Ca2+ concentration in the cytoplasma of cardiomyocytes.
      This is one of the most important reason for the Ca2+ overloading and ultimately
      for heart death. According to authors opinion, beside the dangerous metabolic
      disorders, general membrane damage and extended disturbances in membrane
      functions are also very characteristic for diabetes. The acknowledgement of these
      alterations are very important for the exact planning of the up to date treatment
      of diabetes.

PMID- 11573449
TI  - [Role of thalidomide in the treatment of multiple myeloma].
AB  - Multiple myeloma is a relatively common hematologic malignancy with no definitive
      treatment available. Although, therapy may include allogenic bone marrow
      transplantation, high-dose ablative chemotherapy followed by bone marrow or
      peripheral stem cell transplantation, melphalan/corticosteroid therapy, alpha
      interferon treatment, and combined cytostatic chemotherapy, currently none of
      these alternatives offers cure for the disease. Thalidomide is an infamous
      molecule for its teratogenicity, yet it possesses potent immunomodulatory, anti
      angiogeneic and, in higher concentrations, direct anti-myeloma-cell properties.
      At present, the drug is only approved for the treatment of erythema nodosum of
      leprosy, however, there are several preliminary results that show clinical
      efficacy in multiple myeloma. This drug has especially potent anti-myeloma
      effects in combinations with dexamethasone and certain cytostatic
      chemotherapeutic agents. The effects are evident both in polyresistant, and
      relapsing myeloma, a form with no accepted effective treatment options. In this
      paper, the fundamental molecular and cellular effects of thalidomide are
      summarized then the most important clinical studies with thalidomide are
      reviewed. It is the authors' hope that thalidomide will soon be a full member of
      the medical arsenal in the fight against multiple myeloma.

PMID- 11573450
TI  - [Dermatologic aspects of SAPHO-syndrome].
AB  - SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis) as a new
      disease entity was first described in 1987. The syndrome is characterized by the
      presence of pustular dermatoses together with aseptic osteoarticular lesions. The
      bone involvement includes hyperostosis, aseptic osteomyelitis or arthritis of the
      anterior chest wall, sacroiliac joints or long bones. Skin diseases include acne
      conglobata or acne fulminans, palmoplantar pustulosis and hidradenitis
      suppurativa. Authors describe the dermatological relationship of SAPHO syndrome
      reporting their 7 cases (3 acne fulminans, 4 palmoplantar pustulosis). Authors
      draw attention to the isotretinoin therapy as a possible provoking factor of the
      articular symptoms, and they emphasize the diagnostic role of bone scintigraphy.

PMID- 11573451
TI  - [Effect of continuous enteral feeding on pancreas exocrin function in rats].
AB  - The aim of this study was to examine the effects of continuous enteral feeding
      (CEF) on the exocrine pancreas in rats. Eight male Wistar rats were
      intrajejunally cannulated and CEF was started on postoperative day 6. In 10
      control animals, laparotomy was followed by intragastric feeding (GF) with the
      same nutriment (Osmolite, Abbott, 254 mosm/l) from postoperative day 6. The daily
      discharge was 24 kcal in both groups. After five days of feeding, the pancreas
      was removed, its weight and its protein, DNA, trypsin and lipase contents were
      determined. The results revealed no significant difference in body weight loss
      between the two groups of animals, whereas the pancreas weight/body weight ratio
      was lower (p < 0.01) in the CEF group. The pancreatic protein, DNA, trypsin and
      lipase contents were decreased (p < 0.01) after CEF as compared with the values
      for the GF group.

PMID- 11573452
TI  - [Prinzmetal angina pectoris associated with 3rd degree atrioventricular block].
AB  - The authors report on the case of a 61 year-old female patient who was repeatedly
      taken to hospital because of chest pain and temporary loss of consciousness.
      During her hospitalization there was no ST elevation on the ECG, sinus
      bradycardia, other times atrial fibrillation was detected. The diagnosis was made
      by Holter monitoring three years after the onset of complaints. At this time
      chest pain set in after midnight, which was followed by loss of consciousness.
      Significant ST elevation and IIIrd degree AV block were detected. The
      coronarography showed non-significant coronary stenosis. According to the
      vasospastic patomechanism nitrate, calcium antagonist and acetylsalicylic acid
      therapy was administered and because of the complete AV block leading to syncope
      a VVI, M pacemaker was implanted. During the two years passed since the
      implantation of the pacemaker the patient had chest pain only once and it was not
      accompanied by syncope.

PMID- 11573453
TI  - [Development of the construction of adhesive bridges (Literature review)].
AB  - The author reviews the development of adhesive bridges since since the original
      publication of Rochette. The various abutment preparations (I., II. and III.
      generation) and the changing metal framework design is discussed in depth.

PMID- 11573454
TI  - [Prevalence of congenital hypodontia in the permanent dentition and its
      treatment].
AB  - Congenital aplasia (agenesis) is an important development dental anomaly. There
      is a big discrepancy between the data on the prevalence of aplasia in dental
      literature. The authors analyzed orthopantomograms of 1875 children and
      adolescents at the Department of Dentistry for Children and Orthodontics of
      Semmelweis University. The prevalence of congenital aplasia was found 15.68% (294
      subjects). There was no difference between the sexes. The most frequently missing
      teeth were the upper lateral incisors, the lower second premolars, the upper
      second premolars and the lower central incisors. The highest number of aplasia
      was detected in the second premolars (330 teeth). The frequency of aplasia of the
      molars was 0.74%. Oligodontia was found in 1.12%. The authors present two
      patients with aplasia and the successful treatment of the cases.

PMID- 11573455
TI  - [Classification of epileptic diseases according to potential of fitting with
      dental prosthesis].
AB  - Epileptic patients seem to have generally poorer dental condition in comparison
      with the healthy population for many reasons. It is important to endeavor to
      provide the same dental care to epileptic patients than to others, however
      certain factors in connection with their disease must be taken into
      consideration. Among these, the most important is to concern about the type of
      seizure with special emphasis on the involvement of the masticatory apparatus and
      the chances of oral soft tissue injuries and aspiration. In addition seizure
      frequency and patients' mental compliance might also play a decisive role.
      According to these factors epileptic patients were grouped into four categories
      with special regard to their dental manageability from the prosthodontic point of
      view. The planning of their dental prosthesis was carried out according to the
      Fabian-Fejerdy classification like in case of any other healthy patients.

PMID- 11573456
TI  - [Attention deficit hyperactivity disorder. Literature review for the pediatric
      dentist].
AB  - The purpose of this review was to give a complete summary of the ADHD (Attention
      Deficit Hyperactivity Disorder) for dentists, especially for those who deal with
      dental traumatology. Children with ADH disorder show symptoms of restlessness,
      hyperactivity, impulsive behaviour and inattention often resulting in serious
      dental accidents. The article summarizes the literary data concerning ADH
      Syndrome, presents a typical case and also deals with the dental considerations.

PMID- 11573457
TI  - [Involvement of the temporomandibular joint in rheumatoid arthritis].
AB  - The rheumatoid arthritis is a systemic connective tissue disease, that most of
      the cases involve the temporomandibular joint. The diagnosis of local involvement
      is usually not difficult because the disease often starts in other peripheral
      small joints. The radiographic signs can be observed more frequently than
      clinical and subjective symptoms. The local symptoms are pain, opening
      difficulty, stiffness in the morning and swelling. The maximal mouth opening is
      restricted by the reduced translatory movement of the mandibular condyle. The aim
      of this case presentation is to describe the temporomandibular aspects of the
      rheumatoid arthritis and to suggest the usefulness of the condylar movement
      registration in the diagnostic procedure of the disease.

PMID- 11573458
TI  - [Effect of experimentally induced trauma to the incisors in rats].
AB  - The purpose of this study was to produce developmental lesions of enamel in rats
      by a quick and simple method and to examine the enamel hypoplasia caused by
      trauma. 4-day-old and 3-week-old Wistar rats were used. Trauma was produced by
      needle pricking and hitting on the mandibula. After one week incisors were
      removed together with jaws and prepared for microradiography, X-ray diffraction,
      light microscope and transmission electron microscope examination.
      Microradiographic findings in the needle pricking group revealed hypocalcified
      and hypoplastic enamel. The incidence was 73.7%. In the hitting group of 4-day
      old rats the incidence was lower, 70.0%. Microradiographic findings in this group
      were diffuse hypoplasia in the surface enamel. Hitting of 3-week-old rats
      produced no enamel hypoplasia. Crystallinity of hypoplastic enamel was reduced in
      both a-axis and c-axis direction. Histological findings in 4-day-old rats
      revealed disarranged and detached ameloblasts at location trauma. These results
      indicate that a needle pricking method involving secretory stage ameloblasts of 4
      day-old rat incisors can induce a considerable amount of enamel hypoplasia.

PMID- 11573459
TI  - [Cephalometric aspects of progressive systemic sclerosis--a case report].
AB  - The Progressive Systemic Sclerosos (PSS) is an autoimmune disease which affects
      mainly the middle age groups and is manifested in the fibrosis of different
      internal organs. The disease is important for the dentist because of the
      restricted mouth opening leading to the difficulties in oral hygiene and the
      routine dental treatment. The oral involvement in Progressive Systemic Sclerosis
      has already been studied, and a few alteration and radiological changes were
      detected. However cephalometric analysis of this patient group has not been
      performed up to now. In our study the oral clinical and radiological signs of the
      disease has been described in a patient with PSS. Cephalometric analysis
      (according to Ricketts, modified and to Holdoway) has been used to show the
      radiological anomalies of her jaws and soft tissues. The most important data of
      the jaws were registered in changes of SNB and AB angles. In soft tissues the
      most important cephalometrical changes were in the perioral region probably
      because of the sclerosis. This method (cephalometric method) would be a new
      possibility to describe objectively the clinical signs (mainly the changes in
      soft tissues) of patients with PSS.

PMID- 11573460
TI  - An analysis of substance use among adolescents from smaller places.
AB  - This study examined trends in substance use among 12th grade students who live in
      smaller places. Subjects from smaller places were defined as those residing in
      nonmetropolitan and metropolitan counties who reported growing up on a farm, in
      the country (i.e., living in an unincorporated rural area but not on a farm) or
      in a small town (i.e., living in a place with fewer than 50,000 residents that is
      not a suburb or located next to a larger place). Six types of smaller places were
      created from a cross-tabulation of nonmetropolitan-metropolitan status and where
      subjects reported growing up. Substance-use rates among 12th graders residing in
      these six types of smaller places from 1976 to 1997 at three-year intervals were
      compared, based on data available from the Monitoring the Future study. For past
      year alcohol use, some differences were found by place, with farm youth showing
      the lowest rates. Large differences were exhibited for past-year marijuana use,
      both across nonmetropolitan-metropolitan status and across youth from farm,
      country and small-town locations within nonmetropolitan counties. Rates of past
      year illicit drug use were essentially the same regardless of location. Overall,
      when significant differences were found, most revealed less use for the more
      rural location.

PMID- 11573462
TI  - The impact of immunization record aggregation on up-to-date rates--implications
      for immunization registries in rural areas.
AB  - Problems with poorly documented immunization records may be especially important
      in rural areas. To evaluate the potential impact of a regional registry in a
      rural region, this study quantified the change in documented immunization rates
      for nine primary care sites in rural Colorado resulting from the addition of
      public health department immunization clinic records. Manual chart reviews of
      immunization data were conducted at both private primary care and public health
      department sites in two geographic areas in rural Colorado. Data from private
      primary care sites were matched to data from the public health department sites.
      Immunization up-to-date (UTD) rates at each primary care site were then
      recalculated for 12- and 24-month-olds after including data from public health
      department sites. Of 1,533 children, 469 (31 percent) were given immunizations at
      both a private primary care and a public health department site. The UTD rate
      (3:2:3:2) of 12-month-olds using only data from primary care sites ranged from 32
      to 79 percent. Including the public health department data increased the rates by
      0 to 26 percent (mean = 11 percent) for 12-month-old children. The UTD rate of 24
      month-olds (4:3:1:3 and any Hib on/after 12 months) ranged from 6 to 54 percent
      at the primary care sites. These rates increased by 6 to 21 percent (mean = 12
      percent) when public health department data were added. This "virtual" registry
      combining primary care and public health department data increased calculated
      immunization rates at primary care sites substantially, with a range of 0 to 26
      percent.

PMID- 11573461
TI  - Rural, urban and suburban comparisons of preventive services in family practice
      clinics.
AB  - Numerous studies have compared health services provided in rural and urban areas,
      and overall they have found that utilization is lower in rural areas. A
      significant factor in lower utilization is that rural residents have less access
      to health services. Much less is known about rural and urban utilization
      differences once a patient has access to a service provider. This paper focuses
      on preventive services received when a patient is already in a clinic. Using data
      from an in-depth qualitative study of 16 family practice clinics in Nebraska,
      comparisons of physician-specific preventive service rates are made across three
      geographic categories: rural, urban and suburban. Results from a one-way
      multivariate analysis of variance show that preventive services rates for nine
      services examined were as high or higher in rural areas, suggesting that rural
      health services do not lag for patients with access.

PMID- 11573463
TI  - Itinerant surgical and medical specialist care in Kansas: report of a survey of
      rural hospital administrators.
AB  - In most rural areas, specialist nonprimary care, when available, is provided by
      "itinerant" physicians and surgeons who periodically visit from a distant home
      base. Little is known about current usage and acceptability of itinerant
      specialists in rural communities. Administrators of hospitals in rural and
      frontier Kansas counties were asked to report the frequency of itinerant care in
      their facilities, the home base of each specialist and a listing of procedures
      performed during specialist visits. Administrators were also asked to respond on
      a Likert scale to six questions inviting their assessment of itinerant care.
      Responses were received from 53 of 56 hospitals. All offered at least one monthly
      session of itinerant medical or surgical care. The most common specialties
      represented were cardiology (in 87 percent of hospitals), urology (68 percent),
      orthopedics (68 percent) and radiology (60 percent). General surgeons consulted
      in over 80 percent of responding hospitals. Psychiatrists, dermatologists and
      neurologists were rarely available in the hospitals surveyed. Administrators
      generally rated itinerant care highly, though some expressed concern about
      revenue lost when specialists performed procedures in their home-base office or
      hospital. No associations were found between amount of care offered and potential
      explanatory variables such as hospital size, distance from subregional centers,
      or percentage of patients hospitalized locally. Further study is needed to better
      understand differences in itinerant specialist utilization and acceptance among
      rural Kansas hospitals. Because Kansas demographics are similar to those of many
      other American rural areas, such study may offer insights applicable to other
      regions.

PMID- 11573465
TI  - The economic realities of rural pharmacy practice.
AB  - Rural pharmacy practice is characterized by difficulties in recruiting and
      retaining pharmacists, demanding workloads and financial pressures that exceed
      those felt by pharmacies in urban areas. There is little optimism that these
      harsh realities will soon ease, given the shortage of pharmacists, high drug
      costs, and leverage by third-party payers. These realities should create concern
      among policy-makers for the economic viability of rural pharmacies and for the
      continued ability of pharmacists to provide health care services to residents of
      rural and frontier communities.

PMID- 11573464
TI  - Equipment dealers' perceptions of a community-based rollover protective
      structures promotion campaign.
AB  - Farming is one of the most hazardous occupations, and tractor overturns are the
      leading cause of agricultural fatalities. This article examines a community-based
      injury intervention designed to increase the number of rollover protective
      structures (ROPS) and seat belts on tractors and to promote safe operation of
      farm tractors in two counties. Equipment dealers who sell retrofit ROPS kits to
      farmers were a critical component of the intervention. Interviews were conducted
      with dealers after the 31-month intervention period to understand their
      perceptions, any difficulties they experienced as a result of the project and how
      a similar project could be improved. Comments were analyzed in relation to
      theories of persuasion. Results indicated that dealers believed the intervention
      was successful in producing behavior change among some farmers. Dealers also
      provided important insights into why some farmers continued to resist
      retrofitting tractors with ROPS. Recommendations are offered for designers of
      community-based interventions beyond the ROPS project described here.

PMID- 11573466
TI  - Rural Hospital Flexibility Program: the tracking project reports first-year
      findings.

PMID- 11573467
TI  - Medicare + Choice experiences in rural areas.

PMID- 11573468
TI  - Effects of managed mental health care on service use in urban and rural Maine.
AB  - This study takes advantage of a "natural experiment" resulting from the
      reassignment of all Maine state employees to a managed behavioral health plan in
      December 1992. By comparing mental health claims before and after that date, the
      effects of a behavioral health carve-out on mental health utilization by rural
      and urban beneficiaries were investigated. Following the implementation of the
      carve-out, the penetration rate, defined as the proportion of beneficiaries who
      sought help for an affective disorder, increased significantly in both rural and
      urban areas (P < 0.001). However, the rural penetration rate remained
      significantly lower than the urban rate (before implementation, 25.8 vs. 52.2
      users per 1,000 enrollees, P < 0.001; after implementation, 57.8 vs. 85.8 users
      per 1,000 enrollees, P < 0.001). Similarly, rural utilization rates, defined as
      the average number of outpatient mental health visits per user, were
      significantly lower than urban rates both before and after implementation of the
      carve-out (before, 9.2 us. 12.9 visits per user, P < 0.001; after, 9.8 vs. 13.3
      visits per user, P < 0.001). Before-after differences were not significant. In
      addition, the proportion of mental health care provided in the primary care
      setting increased after implementation of the carve-out (from 9.5 percent of all
      visits before to 12.6 percent of all visits after, P < 0.001). The increase in
      penetration rates can be attributed, in part, to a member education initiative
      undertaken during the transition from fee-for-service to managed care. This type
      of carve-out arrangement does not threaten to reduce access to mental health
      services, provided the managed behavioral health organization (MBHO) managing the
      carve-out is willing to accept primary care practitioners as part of its provider
      network.

PMID- 11573469
TI  - True, false, whatever.

PMID- 11573470
TI  - Uneasily to bed.

PMID- 11573471
TI  - The real 'survivor'.

PMID- 11573472
TI  - A time to honor the dead--and to embrace the living.

PMID- 11573473
TI  - Courage under terrible fire.

PMID- 11573474
TI  - For children's sake.

PMID- 11573475
TI  - Cold sweat and flashback.

PMID- 11573477
TI  - Bibliography. Current world literature. Assessment of nutritional status and
      analytical methods.

PMID- 11573476
TI  - Bristol Royal Infirmary--the aftermath: six pages of analysis.

PMID- 11573478
TI  - Bibliography. Current world literature. Genes and nutrition.

PMID- 11573479
TI  - How effective are guidelines for the management of low back pain?

PMID- 11573480
TI  - Medical errors and medical culture. There is no easy way around taking
      responsibility for mistakes.

PMID- 11573481
TI  - Medical errors and medical culture. Pain relief should have been provided without
      hesitation.

PMID- 11573482
TI  - Medical errors and medical culture. Move from "I" to "we" represents a paradigm
      shift in responsibility.

PMID- 11573483
TI  - Medical errors and medical culture. Changing the culture of blame requires a
      revolution.

PMID- 11573484
TI  - Global campaign to eradicate malaria. Meeting showed scope for scaling up
      campaign.

PMID- 11573485
TI  - Global campaign to eradicate malaria. Malaria is paradigm of an emergent disease.

PMID- 11573486
TI  - Opioids in chronic non-malignant pain. Opioids can cause addiction even in
      patients with pain.

PMID- 11573487
TI  - Opioids in chronic non-malignant pain. Chronic pain should not be undertreated.

PMID- 11573488
TI  - Opioids in chronic non-malignant pain. Don't forget methadone for chronic pain.

PMID- 11573489
TI  - Early growth and coronary heart disease in later life. Analysis was flawed.

PMID- 11573490
TI  - Riluzole for motor neurone disease. Reply from chairman of appraisal committee at
      NICE.

PMID- 11573491
TI  - Any placebo controlled trial of riluzole would surely be unethical now.

PMID- 11573492
TI  - Antidepressant trials generally have methodological defects.

PMID- 11573493
TI  - Doctors should tell patients truth about their waiting lists.

PMID- 11573494
TI  - Equipoise is not synonymous with uncertainity.

PMID- 11573495
TI  - Medical litigation. The ex-barrister's tale.

PMID- 11573496
TI  - Medical litigation. Legal aid is still needed.

PMID- 11573497
TI  - Career advice for doctors with a chronic illness. Occupational health service can
      provide help.

PMID- 11573498
TI  - Career advice for doctors with a chronic illness. You have to do whatever it
      takes to achieve your goal in medicine.

PMID- 11573499
TI  - Drugs are not best for obesity.

PMID- 11573500
TI  - I was obviously fortunate when my salivary gland was removed.

PMID- 11573501
TI  - A poem to benefit health.

PMID- 11573502
TI  - Exercise, not taping, improves outcomes for patients with anterior knee pain.

PMID- 11573503
TI  - Kinaesthetic exercise does not improve outcome (or kinaesthesia) in patients with
      acute whiplash.

PMID- 11573504
TI  - A home program is as effective as in-rooms treatment in the management of distal
      radius fracture.

PMID- 11573505
TI  - Historical and current treatment of calcaneal fractures.

PMID- 11573506
TI  - [History of the Royal Academy of Sciences. Physical explanation of a disease that
      causes plants in the Gastinois to perish, particularly Saffron].

PMID- 11573507
TI  - Case 5: recurrent disease in renal transplantation.

PMID- 11573508
TI  - Surgical evolution: clinical practice catching up to tumor biology in breast and
      colon cancer.

PMID- 11573509
TI  - Gallium diffusion in human root dentin: quantitative measurements by pulsed
      Nd:YAG laser ablation combined with an inductively coupled plasma mass
      spectrometer.
AB  - OBJECTIVE: The purpose of this work was to determine if gallium nitrate placed in
      human root canals would diffuse across root dentin and reach concentrations high
      enough to inhibit osteoclasts (approximately 10(-4) M). BACKGROUND DATA: External
      root resorption by osteoclasts is a common sequela of dental trauma. If not
      detected and treated, it can lead to the loss of a tooth. Gallium has recently
      been reported to inhibit osteoclastic resorption in vitro. METHODS: Roots were
      cleaned and shaped using standard endodontic procedures and the tips sealed with
      cyanoacrylate cement. The root canal space was filled with an aqueous solution of
      1.0 M gallium nitrate chelated with 1.0 M sodium citrate buffer (pH 7.2). The
      roots were then sectioned longitudinally into two equal halves. Each half was
      fixed to a translation stage that moved at a constant rate beneath a frequency
      quadrupled Nd-YAG laser (266 nm) laser that was used to sample the concentration
      of 43Ca, 69Ga, and 71Ga by laser ablation across the thickness of root dentin to
      the periodontal surface. The plume of ablated dentin was swept into an
      inductively heated plasma chamber by argon gas and hence into a mass
      spectrometer. RESULTS: Quantitative analyses of the distribution of gallium
      showed it was highest adjacent to the root canal space and fell as more
      peripheral sites were sampled but then rose slightly at the external boundary of
      the root which is covered with a thin layer of atubular cementum. CONCLUSIONS:
      Even the lowest concentrations of gallium found in peripheral root dentin
      exceeded the 10(-4) M concentration required to inhibit osteoclastic activity.
      This simple endodontic treatment should undergo clinical trials to determine its
      efficacy in vivo. The laser ablation, inductively coupled mass spectrometry
      method is a powerful analytic tool for measuring spatial distribution of
      materials in mineralized tissues.

PMID- 11573510
TI  - Effect of low-level laser radiation on some rheological factors in human blood:
      an in vitro study.
AB  - OBJECTIVE: The purpose of this study was to investigate the in vitro effects of
      low-level laser radiation (LLLR) on some rheological factors of the human blood,
      such as complete blood count (CBC) parameters and blood sedimentation rate (BSR).
      We were mainly concerned with the alterations caused by LLLR action on blood
      cells (erythrocytes and leukocytes) of fresh blood obtained from apparently
      healthy adult patients. We used low doses ranging between 0.80 J x cm(-3) and
      4.40 J x cm(-3), at the very low-power densities of the laser radiation, so as
      not to damage the cell structure and not to alter in an undesired manner their
      functions. METHODS: Blood samples were taken from 22 volunteers. Where health
      problems existed, they were indicated for each case. The parameters mentioned
      above were measured before (control samples) and after irradiation. A He-Ne
      laser, operating in continuous wave, as a radiation source (632.8 nm, 1 mW,
      intensity of 8 x 10(-2) W x sr(-1), mean power density incident on blood samples
      around 30 mW x cm(-2), beam spot diameter 2 mm) was used. The measurements were
      performed immediately after irradiation. Only the erythrocyte complex was
      irradiated. EDTA anticoagulant was used. RESULTS: The measurements using a
      computerized hemoanalyzer type SERONO showed significant differences between
      control and irradiated blood samples concerning the following parameters: RBC (in
      22% of cases), HGB (47.3%), HCT (84.2%), RDW (11%), PLT (5.26%), MPV (33.3%), WBC
      (5.26%), MONO (26.3%), and GRAN (63.15%). In the case of BSR (44%), the
      significant differences were noticed especially in the cases of patients
      suffering from some acute or chronic diseases. Nonsignificant differences were
      noticed in the cases of MCV, MCH, MCHC, RDW, and LYMPH. CONCLUSIONS: This study
      has shown that LLLR, even though used at low doses and low power densities,
      produced some changes of the rheological factors of the blood, as follows: a
      revitalizing and regenerating effect on mitosis stimulation and a nondamaging and
      biostimulating effect on the cell membrane (by keeping unmodified MCV, MCH, and
      MCHC). In 3 cases out of 22, hemolysis (complete or partially) occurred, but we
      are not yet sure whether this was caused by laser exposure or by certain
      environmental physical factors.

PMID- 11573511
TI  - Morphological study of the effects of CO2 laser emitted at 9.3 microm on human
      dentin.
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of dentin
      ablation using a carbon dioxide (CO2) laser emitted at 9.3 microm by scanning
      electron microscopy (SEM) and confocal laser scanning microscopy (CLSM).
      BACKGROUND DATA: There have been no reports on effects of CO2 laser irradiation
      emitted at 9.3 microm on dentin by SEM and CLSM. METHODS: Thirty extracted human
      teeth showing no clinical signs of caries were used. All teeth were horizontally
      sectioned to approximately 200 microm thickness and sections were irradiated
      using a 9.3 microm CO2 laser at different parameters as follows: 26 mJ [energy
      density (ED) 53.0 J/cm2] and 30 mJ (ED 61.1 J/cm2). After laser irradiation,
      samples were treated with sodium hypochlorite, stained using rhodamine-123, and
      observed with CLSM followed by SEM procedures. RESULTS: No craters or cracks were
      observed, but many small molten and rehardened particles were documented on the
      sample surface using SEM. Some small cracks were seen in the subsurface layer,
      and some patent dentinal tubules were detected using CLSM. CONCLUSION: These
      results suggest that laser irradiation at these parameters affected the sample
      surface only (less than 20 microm) and would be less harmful to thermal damage of
      dental pulp for dentin ablation.

PMID- 11573512
TI  - Differences in histochemical characteristics of gingival collagen after ER:YAG
      laser periodontal plastic surgery.
AB  - OBJECTIVE: The aim of this study is to evaluate gingival collagen for the effect
      of treatment with the Erbium:YAG Kesler handpiece. The handpiece is designed for
      gingival resurfacing in cases of hypertrophic gingiva and gingival pigmentation.
      BACKGROUND DATA: Lasers represent recent technological advances that afford new
      options for the treatment of periodontal diseases. However, lasers used for
      esthetic gingival soft tissue resurfacing require careful histopathological
      evaluation of the effects on tissue. In particular, it is important to determine
      the effect of laser irradiation on connective tissue, especially the collagen
      fibers. To date, no stage-wise clinical or histological studies have been
      performed addressing this issue. METHODS: Ten patients underwent irradiation with
      the following parameters: energy per pulse, 500 mJ; repetition rate, 10 pps; spot
      size, 3 mm. Gingival biopsy specimens were derived from 6 patients with
      hypertrophic gingiva and 4 with gingival pigmentation. The patients were examined
      before laser treatment and at 7 and 14 days after laser treatment. The tissues
      were fixed in tymph node revealing solution (LNRS), embedded in paraffin,
      sectioned at 5 microm, and stained with hematoxylin & eosin. The status of
      collagen in the treatment site was examined under polarized light after
      picrosirius red (PSR) staining. PSR is a collagen stain that differentiates
      collagen fiber density or size by means of a spectrum of color changes under
      polarized light. The major colors are red, orange, yellow, and green. RESULTS: We
      found a significant difference in the properties of collagen fibers at the first
      week and at 14 days post-treatment. In the normal gingiva, the predominant
      polarization colors were in the red-orange range, signifying tightly packed,
      mature collagen. During the first postoperative week, collagen fibers exhibited
      polarization colors in the green to green-yellow range, implying loosely packed
      collagen fibers. After 2 weeks, collagen fibers reacquired their preoperative PSR
      characteristics. CONCLUSIONS: We conclude that sequential series of changes
      accompany photothermal treatment of the gingiva. The occurrence of this sequence
      in all successful outcome cases may suggest the importance of these temporally
      sequenced changes in collagen during gum healing. In any event, the status of PSR
      staining of gum collagen provides a useful adjunct in the assessment of gingival
      health.

PMID- 11573513
TI  - Newly induced beta-galactosidase molecules have a higher activity than the
      basally expressed enzyme.
AB  - OBJECTIVE: The objective of this study was to compare the activities of
      individual molecules of induced and basally expressed Escherichia coli beta
      galactosidase. BACKGROUND DATA: Single-molecule assays of enzymes have determined
      that individual molecules are not identical. They differ with respect to
      catalytic rate. The structural cause and cellular role of this microheterogeneity
      is as yet unknown. METHODS: E. coli were grown and induced to produce beta
      galactosidase by treatment with isopropyl-beta-D-thiogalactopyranoside. Cells
      were lysed and the beta-galactosidase assayed with capillary electrophoresis
      instrumentation utilizing post-column, laser-induced fluorescence detection. The
      enzyme obtained from treated cells were compared to that from untreated cells.
      RESULTS: The activity of newly induced beta-galactosidase was found to be
      approximately 20% greater than that of the basally expressed enzyme. This
      measured difference is statistically significant. CONCLUSIONS: Production of beta
      galactosidase in E. coli under differing conditions results in differences in the
      activities of the individual enzyme molecules.

PMID- 11573514
TI  - Morphological study on the capability of Er:YAG laser irradiation for root canal
      preparation.
AB  - OBJECTIVE: The purpose of this study was to evaluate morphologically the
      capability of Er:YAG laser irradiation for root canal preparation in vitro.
      BACKGROUND DATA: There have been no reports on root canal preparation using
      Er:YAG laser irradiation. METHODS: Forty extracted human teeth were divided
      randomly into two groups of 20. Laser irradiation was performed using three
      different sizes of fiber tips at the two different parameters (G 1, 2 Hz and 136
      184 mJ/pulse; G 2, 2 Hz and 170-230 mJ/pulse). After laser irradiation, the teeth
      were bisected longitudinally and observed by stereoscopy and field emission
      scanning electron microscopy (FE-SEM). The time required for preparation in each
      group was recorded and the achievement degree of root canal preparation was
      scored according to our criteria. Statistical analysis of the times was performed
      using one-way analysis of variance (ANOVA). A value of p < 0.01 was considered
      significant. RESULTS: Root canals were prepared using laser irradiation at 50% of
      teeth in G 1 and 40% in G 2. Remnant pulp tissue after laser irradiation was
      observed at 30% of teeth in G 1, but not recognized in G 2. Irradiated areas were
      scale-like and clean, but rough and irregular by FE-SEM. The statistical analysis
      revealed that the time required for preparation at high energies was
      significantly shorter compared with that at low energies (p < 0.01). CONCLUSION:
      These results suggest that Er:YAG laser irradiation is capable of root canal
      preparation if appropriate parameters are selected.

PMID- 11573515
TI  - Laser literature watch.

PMID- 11573516
TI  - AHA Science Advisory on wine and health: A confusing message about alcohol
      consumption.

PMID- 11573517
TI  - Molecular cloning of the mouse homologue of Rab3c.
AB  - Small GTP-binding proteins of the Rab subfamily are key regulators of
      intracellular vesicle transport. Here we report the isolation of a cDNA clone
      encoding the complete Rab3c isoform from mouse embryo using a degenerative PCR
      based approach. Multiple sequence alignment revealed that the predicted amino
      acid sequence was identical to the previously identified rat Rab3c isoform and
      98% identical to the published bovine Rab3c GTPase from brain. Furthermore by in
      situ hybridisation, Rab3c mRNA was detectable within various regions of the
      brain, cartilage and highly enriched within intestinal villi of foetal tissues.
      Chondrocytes in the hypertrophic zone, but not reserve or proliferative zones,
      expressed high levels of Rab3c. This pattern of expression corresponds with the
      genesis of matrix vesicles during endochondral ossification. In all, our results
      suggest that in addition to its functional role during regulated secretion in
      brain, Rab3c may play a part in matrix vesicle trafficking during skeletal
      development.

PMID- 11573518
TI  - Right heart catheterization in intensive care.

PMID- 11573519
TI  - Codeine phosphate in children: time for re-evaluation?

PMID- 11573520
TI  - Dose-dependent prophylactic effect of nicorandil, an ATP-sensitive potassium
      channel opener, on intra-operative myocardial ischaemia in patients undergoing
      major abdominal surgery.
AB  - Nicorandil, a nicotinamide nitrate derivative, relaxes vascular smooth muscle and
      reduces cardiac muscle contractility by increasing membrane potassium
      conductance, probably by activating ATP-sensitive potassium channels. In this
      prospective, randomized, double-blind, placebo-controlled clinical study, we
      examined the dose-dependent prophylactic effect of nicorandil on intra-operative
      myocardial ischaemia in 248 patients who had pre-operative risk factors for
      ischaemic heart disease and were undergoing major abdominal surgery. Patients in
      group HD (n=81) received a bolus dose of nicorandil 0.08 mg kg(-1) and a
      continuous infusion of 0.08 mg kg(-1) h(-1). Patients in group LD (n=87) received
      nicorandil 0.04 mg kg(-1) and 0.04 mg kg(-1) h(-1). Patients in the placebo (P)
      group (n=80) received the same volumes of saline. The patients were monitored
      with a three-lead clinical ECG monitor with an ST trending device from arrival in
      the operating theatre to the end of anaesthesia. Intra-operative myocardial
      ischaemia occurred significantly less frequently in the HD group (one patient,
      1.2%) than in the LD (11 patients, 12.6%) and P groups (21 patients, 26.3%)
      (P<0.01), and in group LD significantly less than in group P (P<0.05).
      Administration of nicorandil had little effect on the patients' heart rate or
      arterial pressure. Three patients in group P and none in either treatment group
      developed myocardial infarction after surgery.

PMID- 11573521
TI  - Prediction of volatile anaesthetic solubility in blood and priming fluids for
      extracorporeal circulation.
AB  - Volatile anaesthetics are often used during cardiopulmonary bypass (CPB). To
      understand the kinetics of inhaled anaesthetics during CPB, anaesthetists should
      understand changes in blood solubility caused by fluid use. We set out to predict
      the solubility of three volatile anaesthetics, desflurane, isoflurane and
      halothane, during CPB by determining: (i) their solubility in fresh whole blood
      and eight CPB priming fluids at 37 degrees C; (ii) the effect of temperature on
      the solubility of these anaesthetics in lactated Ringer's, gelofusin, banked
      blood and plasma; (iii) their solubility in different mixtures of these four
      priming fluids at different temperatures; and (iv) their estimated and actual
      solubility in blood during hypothermic CPB. We calculated solubility using a
      concept of volume fraction partition coefficient and compared estimated and
      measured solubilities. For the three anaesthetics tested, solubilities are in the
      order: fresh whole blood approximately = plasma > banked blood > normal saline
      approximately = lactated Ringer's approximately = gelofusin approximately =
      Haemaccel approximately = hydroxyethyl starch > mannitol. The solubilities of the
      anaesthetics in all priming fluids increased logarithmically at lower
      temperatures (P<0.05). The volume-fraction estimates of the partition
      coefficients were within approximately +/-20% of the measured values for all
      values of solubility. The corresponding estimates of solubility for CPB blood
      samples were between -36% and +24% of the measured values. During normothermic
      CPB, blood solubility of volatile anaesthetics would be unchanged when using
      plasma, slightly reduced when using banked blood and markedly reduced when using
      crystalloids and colloids.

PMID- 11573522
TI  - Compound A production from sevoflurane is not less when KOH-free absorbent is
      used in a closed-circuit lung model system.
AB  - In an in vitro study, less compound A was formed when a KOH-free carbon dioxide
      absorbent was used. To confirm this observation we used a lung model in which
      carbon dioxide was fed in at 160 ml min(-1) and sampling gas was taken out for
      analysis at 200 ml min(-1); ventilation aimed for a PE'CO2 of 5.4 kPa. The soda
      lime canister temperatures in the inflow and outflow ports (Tin and Tout) were
      recorded. In six runs of 240 min each, a standard soda lime, Sodasorb (Grace,
      Epernon, France) was used and in eight runs KOH-free Sofnolime (Molecular
      Products, Thaxted, UK) was used. Liquid sevoflurane was injected using a syringe
      pump to obtain 2.1% E'. Compound A was measured by capillary gas chromatography
      combined with mass spectrometry. Median (range) compound Ainsp increased to a
      maximum of 22.7 (7.9) ppm for Sodasorb and 33.1 (20) for Sofnolime at 60 min and
      decreased thereafter; the difference between groups was significant (P<0.05) at
      each time of analysis up to 240 min. The canister temperatures were similar in
      both groups and increased to approximately 40 degrees C at 240 min. Contrary to
      expectation, compound A concentrations were greater with the KOH-free absorbent
      despite similar canister temperatures with both absorbents.

PMID- 11573523
TI  - Arterial to end-tidal carbon dioxide tension difference in children with
      congenital heart disease.
AB  - In children with congenital cyanotic heart disease, right-to-left intracardiac
      shunting causes an obligatory difference between arterial and end-tidal carbon
      dioxide tension (PaCO2-PE'CO2) as venous blood, rich in carbon dioxide, is added
      to the arterial circulation. This obligatory PaCO2-PE'CO2 difference, which can
      be predicted from knowledge of oxygen saturation, haemoglobin concentration and
      PaCO2, increases as oxygen saturation decreases, most markedly when the
      haemoglobin concentration is high. A second possible cause of the PaCO2-PE'CO2
      difference is the effect of pulmonary hypoperfusion caused by the shunt. We
      studied 60 children undergoing cardiac surgery and compared the predicted the
      PaCO2-PE'CO2 difference with measured values to investigate the extent to which
      additional factors influence the clinically observed PaCO2-PE'CO2. In many
      children, observed values were much greater than predicted, which is compatible
      with some degree of pulmonary hypoperfusion. However, this was not felt to
      represent the complete picture in all patients. Another cause of ventilation
      perfusion mismatch was suspected in those children who showed a considerable
      improvement in oxygen saturation during ventilation with an increased FIO2. We
      believe that pulmonary congestion caused by large left-to-right shunts may
      further increase the PaCO2-PE'CO2 difference.

PMID- 11573524
TI  - Biphasic EEG changes in relation to loss of consciousness during induction with
      thiopental, propofol, etomidate, midazolam or sevoflurane.
AB  - The time course of four EEG effect variables, amplitude in the 2-5 Hz and in the
      11-15 Hz band, spectral edge frequency 95% (SEF95), and bispectral index (BIS),
      in response to increasing concentrations of thiopental, propofol, etomidate,
      midazolam, or sevoflurane during a 10 min induction of anaesthesia was studied in
      25 patients to determine the existence of a biphasic effect and to study the
      relationship of the EEG effect to the moment of loss of consciousness. A biphasic
      effect, that is, an initial increase of the effect variable followed by a
      decrease at higher concentrations, during the transition from consciousness to
      unconsciousness was found in EEG amplitude (both frequency bands) and in SEF95
      for all anaesthetics except midazolam. There was a concentration-related decrease
      in BIS for all anaesthetics. There was no consistent relationship between the
      time of occurrence of the peak EEG effect, or the value of the EEG variable and
      the moment of loss of consciousness. With rapidly changing drug concentrations
      during the induction of anaesthesia, none of these EEG effect variables could be
      correlated to the moment of loss of consciousness.

PMID- 11573525
TI  - Recovery from propofol anaesthesia supplemented with remifentanil.
AB  - We have examined the effects on recovery end-points of supplementation of a
      propofol-based anaesthetic with remifentanil. After induction of anaesthesia with
      propofol and remifentanil 1.0 microg kg(-1), 15 patients each were randomly
      allocated to target plasma propofol concentrations of 2, 3, 4 or 5 microg ml(-1)
      for maintenance of anaesthesia. Remifentanil was administered by infusion for
      supplementation in doses required for maintenance of adequate anaesthesia. All
      patients received 50% nitrous oxide in oxygen and ventilation was controlled. The
      total amount of drugs used and times to different recovery end-points were
      recorded. Cognitive function was also assessed using a Mini-Mental State
      questionnaire. The median dose of remifentanil for maintenance of adequate
      anaesthesia (excluding the initial bolus dose) in the four groups was 0.21, 0.15,
      0.11 and 0.13 microg kg(-1) min(-1) respectively (P=0.0026). The median times to
      eye opening and orientation were shortest in the 2 microg ml(-1) group [6.0 and
      6.5 min, 8.5 and 10.8 min, 13.4 and 15.8 min, and 14.2 and 19.5 min respectively
      in the propofol 2, 3, 4, and 5 microg ml(-1) groups respectively (P<0.001)]. The
      times to discharge from the recovery ward and the Mini-Mental State scores were
      not significantly different.

PMID- 11573526
TI  - Post-operative recovery after inguinal herniotomy in ex-premature infants:
      comparison between sevoflurane and spinal anaesthesia.
AB  - We prospectively studied the post-operative recovery profile of 28 ex-premature
      infants undergoing inguinal herniotomy. All infants had a post-conceptual age of
      less than 46 weeks at the time of surgery and were randomized to receive either
      sevoflurane (group 1, 14 patients) or spinal anaesthesia (group 2, 14 patients).
      All patients received supplemental caudal analgesia before skin incision.
      Cardiorespiratory function was continuously recorded in all patients before and
      after surgery. A blinded observer analysed each paired recording for predefined
      episodes of apnoea, hypoxaemia or bradycardia and the reports were used to
      compare the two groups. Spinal anaesthesia was attempted unsuccessfully in four
      patients in group 2. Five patients in group 1 demonstrated an 'excess' number of
      episodes (median 4, range 3-12) of clinically silent post-operative
      cardiorespiratory complications. ('Excess' in our study was defined as a 3-fold
      or greater increase in the number of post-operative episodes of bradycardia or
      apnoea relative to pre-operative occurrence). Three of these patients had pre
      existing abnormal respiratory function and accounted for 80% of the episodes
      (26/32) of post-operative bradycardia and all five episodes of post-operative
      apnoea identified. All episodes of bradycardia and apnoea were temporally
      unrelated. None of the remaining patients in group 2 demonstrated an unacceptable
      number of post-operative cardiorespiratory complications. Our limited study
      suggests that general anaesthesia with an inhalational agent such as sevoflurane
      may induce or unmask abnormalities of cardiopulmonary function in predisposed
      infants. Spinal anaesthesia may be preferable but it is potentially stressful for
      the infant and associated with a clinically significant failure rate.

PMID- 11573527
TI  - Evaluation of pre-emptive intramuscular phenylephrine and ephedrine for reduction
      of spinal anaesthesia-induced hypotension during Caesarean section.
AB  - Pre-emptive intramuscular (i.m.) vasopressors were evaluated in 108 patients
      undergoing elective Caesarean section under spinal anaesthesia, assigned to four
      groups in a randomized, double-blind, placebo-controlled study. Group 1 received
      pre-emptive phenylephrine 4 mg i.m., group 2 received phenylephrine 2 mg i.m.,
      group 3 received ephedrine 45 mg i.m., while controls received an i.m. injection
      of saline, all given immediately after induction of spinal anaesthesia.
      Hypotension was defined as a 25% decrease in mean arterial pressure (MAP). Rescue
      intravenous (i.v.) boluses of ephedrine were given if the patient was hypotensive
      or reported nausea, vomiting or dizziness. The incidence of hypotension was 33%
      in the phenylephrine 4 mg group compared with 70% in the control and
      phenylephrine 2 mg groups (P=0.03), and 48% in the ephedrine 45 mg group. The
      phenylephrine 4 mg and ephedrine 45 mg groups had a significantly lower
      percentage reduction in MAP (-21 (SD 14)% and -22 (14)%) compared with controls (
      32 (18)%, P=0.04). They also had a lower total dose of rescue i.v. ephedrine
      (15.7 (15.7) mg and 15.8 (15.6) mg) compared with controls (28.8 (20.6) mg,
      P=0.02). We conclude that pre-emptive i.m. phenylephrine 4 mg and ephedrine 45 mg
      reduce the severity of hypotension and the total dose of rescue i.v. ephedrine
      during spinal anaesthesia for Caesarean section.

PMID- 11573528
TI  - I.v. ketoprofen for analgesia after tonsillectomy: comparison of pre- and post
      operative administration.
AB  - We have evaluated the safety and efficacy of ketoprofen during tonsillectomy in
      106 adults receiving standardized anaesthesia. Forty-one patients received
      ketoprofen 0.5 mg kg(-1) at induction ('pre' ketoprofen group) and 40 patients
      after surgery ('post' ketoprofen group), in both cases followed by a continuous
      ketoprofen infusion of 3 mg kg(-1) over 24 h; 25 patients received normal saline
      (placebo group). Oxycodone was used for rescue analgesia. Patients in the
      ketoprofen groups experienced less pain than those in the placebo group. There
      was no difference between the study groups in the proportion of patients who were
      given oxycodone during the first 4 h after surgery. However, during the next 20
      h, significantly more patients in the placebo group (96%) received oxycodone
      compared with patients in the 'pre' ketoprofen group (66%) and the 'post'
      ketoprofen group (55%) (P=0.002). Patients in the placebo group received
      significantly more oxycodone doses than patients in the two ketoprofen groups
      (P=0.001). Two patients (5%) in the 'pre' ketoprofen group and one (3%) in the
      'post' ketoprofen group had post-operative bleeding between 4 and 14 h. All three
      patients required electrocautery.

PMID- 11573529
TI  - Analysis of the French health ministry's national register of incidents involving
      medical devices in anaesthesia and intensive care.
AB  - This study details all incidents involving medical devices used in anaesthesia
      and intensive care reported to the relevant authorities in France in 1998. There
      were 1004 reports during that year. Incidents were classified as serious (harmful
      to patients) in 11% of cases; death resulted in 2% of cases. Equipment for
      ventilation and infusion, and monitors of all kinds, accounted for most of the
      reports, representing 37%, 30% and 12%, respectively, of all reports. The leading
      causes of failure varied according to the category of device. User errors,
      quality control problems during production of the device and design faults were
      the three main causes. The problems identified during the study period enabled
      the faulty medical devices to be improved in 12-44% of cases. We conclude that
      post-marketing vigilance is a useful way of improving the quality of medical
      devices.

PMID- 11573530
TI  - Differential nitric oxide synthase activity, cofactor availability and cGMP
      accumulation in the central nervous system during anaesthesia.
AB  - We investigated the effects of anaesthesia on dynamic nitric oxide production,
      concentrations of tetrahydrobiopterin and the accumulation of cyclic GMP (cGMP)
      in the rat central nervous system (CNS). Rats were assigned to anaesthesia with
      halothane, isoflurane, pentobarbital, diazepam, ketamine or xenon (n=6 per
      group). After 30 min, [14C]L-arginine (i.v.) was given and, after a further 60
      min of anaesthesia, rats were killed and exposed immediately to focused microwave
      radiation. After removal of the brain and spinal cord, nitric oxide production
      from radiolabelled arginine (and hence nitric oxide synthase activity during
      anaesthesia) was measured as [14C]L-citrulline by scintillation counting. cGMP
      was determined by enzyme immunoassay and tetrahydrobiopterin by fluorescence
      HPLC, in brain regions and the spinal cord. Nitric oxide synthase activity was
      similar in all brain regions but was lower in the spinal cord, and was unaffected
      by anaesthesia. cGMP was similar in all areas of the CNS and was significantly
      decreased in rats anaesthetized with halothane. Isoflurane produced similar
      effects. In contrast, ketamine and xenon anaesthesia increased cGMP in the spinal
      cord, brainstem and hippocampus. Diazepam and pentobarbital had no effect.
      Tetrahydrobiopterin concentrations were similar in all areas of the CNS and were
      increased in the cortex and hippocampus after anaesthesia. We have shown profound
      differential effects of anaesthesia on the nitric oxide pathway in the rat CNS.

PMID- 11573531
TI  - Suppressive effect of nitrous oxide on motor evoked potentials can be reversed by
      train stimulation in rabbits under ketamine/fentanyl anaesthesia, but not with
      additional propofol.
AB  - The effect of nitrous oxide on myogenic motor evoked potentials (MEPs) after
      multipulse stimulation is controversial. We investigated the effects of propofol
      in this paradigm. MEPs were elicited electrically by a single pulse and by trains
      of three and five pulses in rabbits anaesthetized with ketamine and fentanyl.
      Nitrous oxide 30-70% was given and MEPs were recorded. After washout of nitrous
      oxide, propofol was given as a bolus of 10 mg kg(-1) followed by 0.8 (n=9) or 1.6
      mg kg(-1) min(-1) (n=8) as a continuous infusion. Nitrous oxide was then re
      administered and MEPs were recorded. Without propofol, nitrous oxide
      significantly reduced the amplitude of MEPs dose-dependently, but this effect was
      reversed by multipulse stimulation. Administration of low-dose propofol enhanced
      nitrous oxide-induced suppression, and this effect was reversed by five-pulse
      stimulation. However, high-dose propofol produced a greater increase in
      suppression, such that even five-pulse stimulation did not overcome the
      suppression. The results suggest that the degree of reversal of nitrous oxide
      induced MEP suppression produced by multipulse stimulation is affected by the
      administration of propofol.

PMID- 11573532
TI  - Evaluation and comparison of the pharmacokinetic and pharmacodynamic properties
      of allopregnanolone and pregnanolone at induction of anaesthesia in the male rat.
AB  - We have evaluated and compared the pharmacokinetic and pharmacodynamic properties
      of allopregnanolone and pregnanolone at induction of anaesthesia in male rats. A
      threshold method was used, and the first burst suppression period of 1 s or more
      in the EEG was selected as the end-point after fairly slow infusions. An optimal
      dose of 4.0 mg kg(-1) min(-1) was noted for both steroids. Brain concentrations
      were low at low infusion rates, indicating that acute tolerance was not
      occurring. Significant positive correlations were noted between dose rate and
      serum concentrations of allopregnanolone (r = 0.94, P<0.001) and pregnanolone (r
      = 0.88, P<0.001). Such correlations were also seen in striatum, cerebellum,
      cortex and muscle for both steroids (P<0.01). Despite changing infusion rates,
      the concentrations of both steroids in brainstem, hippocampus and fat remained
      stable. Because no correlation between infusion rate and steroid concentration
      was noted in the brainstem and hippocampus, these two brain areas may be regarded
      as primary sites of action for allopregnanolone and pregnanolone. Pregnanolone
      concentrations in the brainstem and hippocampus were significantly higher than
      those of allopregnanolone, suggesting that allopregnanolone was more potent than
      pregnanolone in inducing anaesthesia.

PMID- 11573533
TI  - Codeine phosphate in paediatric medicine.

PMID- 11573535
TI  - Effects of hypoxia and isoflurane on liver blood flow: the role of adenosine.
AB  - We investigated the role of endogenous adenosine in mediating the effects of
      hypoxia and isoflurane on portal tributary blood flow (PTBF) and hepatic arterial
      blood flow (HABF) in rats. Liver blood flows were determined using radiolabelled
      microspheres. Hypoxia resulting from the exposure of rats to an atmosphere
      containing 15% oxygen for 30 min decreased PTBF (23%) (P<0.05) and cardiac index
      (15%) (P<0.05), and increased HABF (78%) (P<0.05). Isoflurane (1.4 vol%)
      increased HABF in both normoxic and hypoxic conditions but did not affect PTBF.
      The adenosine receptor antagonist 8-phenyltheophylline attenuated the hypoxia
      induced increase in HABF but did not affect that resulting from the
      administration of isoflurane. In conclusion, in contrast to the increase in HABF
      induced by hypoxia, that induced by isoflurane appears to be independent of
      endogenous adenosine.

PMID- 11573534
TI  - Predicted effect compartment concentration of thiopental at loss of eyelash
      reflex.
AB  - We derived the predicted effect compartment concentration of thiopental, at loss
      of the eyelash reflex, following three different injection regimens. Sixty
      patients were given thiopental for induction of anaesthesia. Twenty patients
      received multiple small boluses, 20 patients received a single bolus and 20
      patients received an infusion. Computer simulation was then used to derive the
      effect compartment concentration. The median concentration was not significantly
      different between the three groups. EC50, derived after combining all three
      groups was 11.3 microg ml(-1). The EC05-EC95 range was 6.9-18.3 microg ml(-1),
      suggesting wide inter-individual variation.

PMID- 11573536
TI  - Heterogeneous distribution of cardioplegic solution in pigs.
AB  - Septal dyskinesia in the left ventricle is detected frequently in many patients
      after open-heart surgery. The present study was designed to determine whether the
      antegrade delivery of cardioplegic solution to the regional wall categorized in
      echocardiography is homogeneous, and whether the distribution to the septal wall
      differs from that to the lateral wall in the absence of coronary artery disease.
      To assess these hypotheses quantitatively, radioactive microspheres were mixed
      into the cardioplegic solution and infused by an antegrade method in eight normal
      pigs. The cardioplegic distribution to the septal wall was significantly less
      than to the lateral wall close to the base of the left ventricle (P<0.05).
      Therefore, antegrade perfusion of cardioplegic solution was non-uniformly
      distributed to the regional and transmural wall of normal pig hearts. Absence of
      functional correlation was a limitation of this study. However, these findings
      suggest that inadequate protection of the ventricular septum by antegrade
      cardioplegia might be an explanation for the abnormalities of septal wall motion
      after open-heart surgery.

PMID- 11573537
TI  - Liver transplantation for massive hepatic haemangiomatosis causing restrictive
      lung disease.
AB  - A 34-yr-old man with hepatic haemangiomatosis presented for orthotopic liver
      transplantation. His massively distended abdomen caused thoracic compression and
      severe restrictive lung disease. Respiratory failure was the principal indication
      for transplantation. Increased airway pressures, pulmonary hypertension, systemic
      hypotension caused by aorto-caval compression, and blood loss, complicated the
      intra-operative anaesthetic management. Weaning from mechanical ventilation was
      impaired by acute and chronic metabolic alkalosis, and diaphragmatic laxity.

PMID- 11573538
TI  - Undiagnosed cardiomyopathy in a neonate: significance of low oxygen saturation
      during anaesthesia.
AB  - A case study is described of a 7-day-old full term baby with bilateral congenital
      cataracts who underwent surgical removal of both cataracts 2 days apart. Problems
      with oxygen saturation during and after the first anaesthetic prompted further
      investigation that revealed a non-obstructive hypertrophic cardiomyopathy. The
      significance and possible causes of low oxygen saturation in a previously healthy
      neonate during anaesthesia are discussed. The likely diagnosis of Sengers
      syndrome, and the evaluation of asymptomatic babies with cardiac pathology are
      discussed.

PMID- 11573539
TI  - Multiple acyl-CoA dehydrogenase deficiency: a rare cause of acidosis with an
      increased anion gap.
AB  - Metabolic acidosis is encountered frequently in intensive care and common causes
      include lactic acidosis, ketoacidosis, or renal failure. We describe a patient
      presenting to intensive care with a rare cause of metabolic acidosis associated
      with an increased anion gap: multiple acyl-CoA dehydrogenase deficiency. The
      pathophysiology of this condition is discussed along with potential treatment
      options.

PMID- 11573540
TI  - Subarachnoid haemorrhage following spinal anaesthesia in an obstetric patient.
AB  - We describe an obstetric patient who presented for removal of a retained
      placenta. After insertion of the spinal anaesthetic, she developed a severe
      headache, and a subarachnoid haemorrhage was diagnosed. We discuss the
      differential diagnosis of the headache, the occurrence of intracranial
      haemorrhages after dural puncture and the future management of this patient.

PMID- 11573541
TI  - Assessment instruments used during anaesthetic simulation: review of published
      studies.
AB  - This review was undertaken to discover what assessment instruments have been used
      as measures of performance during anaesthesia simulation and whether their
      validity and reliability has been established. The literature describing the
      assessment of performance during simulated anaesthesia amounted to 13 reports
      published between 1980 and 2000. Only four of these were designed to investigate
      the validity or reliability of the assessment systems. We conclude that the
      efficacy of methodologies for assessment of performance during simulation is
      largely undetermined. The introduction of simulator-based tests for certification
      or re-certification of anaesthetists would be premature.

PMID- 11573542
TI  - Pulmonary artery catheterization and mortality in critically ill patients.

PMID- 11573543
TI  - Lymphatic drainage of the thoracic paravertebral space.

PMID- 11573544
TI  - Anaesthetic management of lobectomy for lung abscess or bronchopleural fistula.

PMID- 11573545
TI  - Effects of isoflurane, sevoflurane and propofol on jugular venous oxygen
      saturation.

PMID- 11573546
TI  - Adult epiglottitis: an under-recognized, life threatening condition.

PMID- 11573547
TI  - Adult epiglottitis: an under-recognized, life threatening condition.

PMID- 11573548
TI  - Post-operative nausea and vomiting--time for balanced antiemesis.

PMID- 11573549
TI  - Post-operative nausea and vomiting--time for balanced antiemesis.

PMID- 11573551
TI  - Preventing epidural catheter obstruction.

PMID- 11573550
TI  - Publications on paediatric anaesthesia.

PMID- 11573552
TI  - Arteether in therapy of malaria.

PMID- 11573554
TI  - Clinical characteristics, pulmonary function abnormalities and outcome of
      prednisolone treatment in 106 patients with sarcoidosis.
AB  - The clinical profile of one hundred and six biopsy proved patients with
      sarcoidosis is reported from New Delhi. The disease occurred more frequently in
      males (68 of the 106; 64%) in their fifth decade. Dry cough (83%), exertional
      dyspnoea (61%), fever (56%) and joint pains (44%) were frequent symptoms.
      Hepatomegaly (45%), peripheral lymphadenopathy (45%), cutaneous involvement
      (42%), presence of crepitations (36%) were frequent signs. In addition, ocular
      symptoms (18%), parotid gland enlargement (12%), facial nerve palsy (8%) were
      observed. Audible wheeze was present in nine patients. Radiologically, 25 (24%),
      67 (63%) and 14 (13%) of patients belonged to stage I, II and III respectively at
      presentation. More than one sibling was involved in six families. Pulmonary
      functions revealed mixed obstructive and restrictive ventilatory defect. However,
      obstructive ventilatory defect was predominant. Systemic steroids were used in 81
      patients who regularly followed up. Frequent relapses occurred on tapering off or
      stopping the corticosteroids in 21 patients. History of malaise (p < 0.05),
      presence of crepitations (p < 0.05), wheezing (p < 0.05), peripheral blood
      eosinophilia (p < 0.05) and FEV1/FVC (%) < 65% of the predicted value (p < 0.05),
      were independent predictors of relapse. Hyperuricaemia, hitherto unreported in
      patients with sarcoidosis was observed in 41% of patients for whom values were
      available. Two patients died; one from cardiomyopathy and another from stroke. In
      summary, constitutional symptoms such as fever, weight loss and pulmonary
      infiltrates, were more frequently encountered in Indian patients with sarcoidosis
      as compared to western studies. A high index of clinical suspicion and
      histopathological confirmation early in the illness are required to ascertain the
      diagnosis lest these patients will get treated as tuberculosis with potentially
      hepatotoxic drugs.

PMID- 11573553
TI  - A multicentric study with arteether in patients of uncomplicated falciparum
      malaria.
AB  - Two hundred and sixty seven patients of uncomplicated P. falciparum malaria
      completed study in a multicentric phase III clinical trial of Arteether.
      Arteether was given intramuscularly in a dose of 150 mg daily for three
      consecutive days. Each patient was followed upto 28 days of alpha, beta arteether
      therapy. The cure rate was 97% with fever clearance time between 1-7 days (24-168
      hours) and parasite clearance time between 1-3 days (24-72 hours). Parasite
      reappearance rate was found to be 3% and reported at only three of the centres.
      Following the treatment no adverse effect was observed on haematological,
      biochemical and vital clinical parameters.

PMID- 11573555
TI  - A study of insulin resistance in subjects with acanthosis nigricans.
AB  - AIM: To study the prevalence of insulin resistance (IR) and its sequelae in
      patients with acanthosis. METHODOLOGY: Thirty six patients (28 females; eight
      males) with biopsy proven acanthosis nigricans and eight controls were evaluated
      for insulin sensitivity (IS) by estimating (a) the glucose and insulin responses
      to a 75 gm glucose load (Oral glucose tolerance test-OGTT), (b) the glucose
      disposal rate (GDR) during an intravenous insulin tolerance test (ITT). Serum
      androgen levels (testosterone--Te, androstenedione--ASD, Dehydro-epiandrosterone
      sulphate--DHEAS) were estimated in the basal state and 60 min after a bolus of
      insulin. Thyroid function tests (tri-iodo-thyronine--T3, thyroxine--T4, thyroid
      stimulating hormone--TSH) were performed in all subjects. RESULTS: The acanthotic
      population, overall had insignificant hyperglycemia (Area under curve of glucose-
      AUC-G : 17,745.5 +/- 847.5 v/s 11,051.3 +/- 274.5 mg/dl/min) and hyperinsulinemia
      (Area under curve of insulin -AUC-I: 20,825.2 +/- 1,287.7 v/s 6,340.1 +/- 984.2
      microlU/ml/min) compared to controls during OGTT. Eight patients with acanthosis
      nigricans had impaired glucose tolerance and eight had overt diabetes using WHO
      criteria. 69.4% of the acanthotic subjects were obese and 13.9% (5/36) were
      hypertensive. Thyroid dysfunction was present in three (one had hypothyroidism
      and two had thyrotoxicosis). Reproductive disorders--menstrual irregularity
      (46.5%), amenorrhea (21.4%), hirsuitism (21.4%) and infertility (3.6%) was
      encountered in a significant number of acanthotics. Acanthotics overall had
      statistically higher levels of androgens; Te (females)--0.74 +/- 0.09 v/s 0.27 +/
      0.09 ng/ml (p < 0.005), ASD--1.8 +/- 0.21 v/s 0.94 +/- 0.2 ng/ml (p < 0.005) and
      DHEAS--1,880.8 +/- 216.3 v/s 772.8 +/- 210.4 ng/ml (p < 0.005). An elevated DHEAS
      correlated positively to body mass index (BMI) and android obesity. Serum Te
      levels correlated positively with GDR. Serum insulin levels increased
      progressively with obesity and acanthosis. Serum insulin was associated with
      progressive worsening of hyperandrogenism (as seen in non-obese controls, non
      obese and obese acanthotics). CONCLUSIONS: Subjects with acanthosis nigricans
      should be screened for insulin resistance and its clinical and metabolic
      sequelae. Thyroid dysfunction should be sought in these subjects as it can be
      easily treated.

PMID- 11573556
TI  - Diabetes mellitus in Dombivli--an urban population study.
AB  - OBJECTIVE: The present study was undertaken with the following aims and
      objectives. a) To determine the prevalence of diabetes. b) To compare the
      prevalence of newly diagnosed diabetic subjects, diagnosed by the ADA and WHO
      criteria. c) To determine to what extent prevalence rates are affected by gender,
      age and body mass index. METHODS: The study population consisted of 520 subjects
      aged 20 years and above selected by random sampling. Blood glucose both fasting
      and post glucose (75 gms) two hours sample were analyzed. Baseline clinical data
      like height, weight and blood pressure were recorded. Known cases of diabetes
      were excluded from the study. RESULTS: The prevalence of diabetes (fasting blood
      glucose) as per WHO criteria was 4.61% while it was 7.5% as per ADA criteria. The
      prevalence according to the two hour glucose reading was 6.15%. The mean glucose
      level increase with age. With increasing BMI the percentage of diabetic subjects
      also increases. The prevalence of impaired glucose tolerance (IGT) was 8.6% in
      subjects below 50 years and 13.4% in subjects older than 50 years. IGT values
      also increase with increasing age and BMI. 1.3% of subjects had normal fasting
      glucose level (< 126 mgm%) but high post glucose levels (> 200 mgm%).
      CONCLUSIONS: The prevalence of diabetes and IGT is higher as compared to earlier
      studies. The mean blood glucose and IGT increase with increasing age and BMI.
      Several subjects had normal fasting blood glucose but increased two hour blood
      glucose level indicating that fasting glucose alone should not be used to
      diagnose DM. Urbanization and life style of residents of Dombivli contribute to
      the high prevalence.

PMID- 11573557
TI  - DiabCare Asia--India Study: diabetes care in India--current status.
AB  - AIM: To investigate the relationship between diabetes control, management and
      late complications in a subset of urban Indian diabetes population treated at
      tertiary diabetes care centres and measure the quality of management to set
      benchmarks for future improvement. METHODOLOGY: The study population consisted of
      100 consecutive review patients treated for more than one year at each of the 26
      participating centres. HbA1c was estimated centrally by Bio-Rad Variant method.
      The methods used to diagnose diabetic complications varied among centres,
      depending on the doctor's standard clinical examination. A more detailed
      methodology was eschewed for reason of brevity of the data collection form, and
      lack of standardisation of methods. Similarly, the assessment of renal function
      was performed via a variety of methods, namely dipstick proteinuria, a 24 hour
      urinary excretion assay, presence of microalbuminuria and serum creatiine
      concentration; retinopathy was detected using fundoscopy. Data was collected in a
      standardized data collection form, entered into an SAS database, validated and
      descriptive analysis performed. RESULTS: A total of 2,269 subjects with valid
      relevant data formed the study population. Subjects had a mean age of 53.3 +/- 13
      years. The mean age at onset of diabetes was 43.6 +/- 12.2 years, with a mean
      diabetes duration of 10.0 +/- 6.9 years. Type 2 diabetics constituted 90.6% of
      the patients. Approximately half the patients had poor control (HbA1c > 2% points
      above upper limit of normal and FBG > 139 mg/dl). Mean HbA1c (central laboratory)
      was 8.9 +/- 2.1% and FBG 150 +/- 59 mg/dl. Over 54% patients had severe late
      complications, apart from a high frequency of associated hyperlipidemia. Mean
      HbA1c level and frequency of complications was higher in patients with longer
      diabetes duration. Frequency of self-monitoring was low. Only 4% of patients were
      on diet therapy, 53.9% were receiving oral hypoglycemic agents (OHAs), 22% were
      receiving insulin and 19.8% a combination of insulin and OHAs. Frequency of
      insulin usage was higher amongst patients with longer diabetes duration.
      CONCLUSIONS: This large multi-centre collaborative observational study shows that
      type 2 diabetes begins at an early age amongst Indians. With increasing duration
      of diabetes, glycemic control deteriorates leading to late complications.
      Diabetes care in India leaves much to be desired. Concerted efforts to increase
      awareness amongst health professionals to improve diabetes care are urgently
      needed. The study by increasing awareness about the current status of diabetes
      care provides a useful benchmark to plan future improvements.

PMID- 11573558
TI  - Seizures in hyperglycemic patients.
AB  - AIM OF STUDY: To study the pattern of seizures in hyperglycemic patients and its
      correlation with serum osmolality, blood sugar and serum sodium. MATERIALS AND
      METHODS: (Study period June 1999-June 2000) Forty patients who presented with
      first time seizures and who were detected to be diabetic were included in the
      study. All patients had detailed history, clinical examination blood sugar, BUN,
      serum electrolytes, serum osmolality, serum calcium estimation. EEG and CT head
      scan was also done. The seizures were classified as per ILAE classification
      (1981). The study group was further divided into Group A--those with normal CT (n
      24) and Group B-- those showing infarcts in CT scan (n 16). The control group (n
      40) were matched for age and had first occurrence of seizures and CT showed
      infarct and were euglycemic. All the investigations were done for the control
      group as well. Statistical analysis was done using ANOVA. RESULTS: None of the
      patient had diabetic ketoacidosis. Patients in study group had statistically
      significant incidence of (1) Focal seizures with or without generalisation
      (100%); (2) Visual hallucination (25%); (3) Epilepsia partialis continua (20%).
      Comparing the subgroups (A and B) complex partial seizures and visual
      hallucination was significant at 5% level in the group A (NKH with normal CT).
      Ninety percent in the study group had increased serum osmolality (Vs 22.5% in the
      control group). Duration (eight days Vs 1) and frequency (15 per day vs 1.45)
      were positively correlated with RBS > S.osmolality > S.sodium. CONCLUSION: 1.
      Long duration and frequent focal motor seizures with or without secondary
      generalisation occurs in NKH which at times may be the first manifestation of DM.
      2. Complex partial seizures, visual hallucination and epilepsia partialis
      continua are more common in NKH patients than in euglycemic patients. 3. There is
      positive correlation of blood sugar, S.osmolality and S.sodium with frequency and
      duration of seizures. RBS > S.osmolality > S.Na. 4. Correction of hyperglycemia
      is the main stay of management of seizures. 5. Movement induced seizures which is
      specific for NKH is a rarity.

PMID- 11573559
TI  - Follicular adenoma of thyroid associated with mediastinal malignant
      hemangioendothelioma, masquerading as malignant retrosternal goiter.

PMID- 11573560
TI  - Auscultation in the new millennium.

PMID- 11573561
TI  - Probiotics in health and diseases.

PMID- 11573562
TI  - Diagnostic approach to thyroid goiter.

PMID- 11573563
TI  - Intrasacral meningocele with tethered cord syndrome.
AB  - We present a 65 year old, relatively asymptomatic man, who was found to have an
      intrasacral meningocele with tethered cord syndrome on Magnetic Resonance Imaging
      (MRI). Incidental detection of this entity at such an old age is very unusual.

PMID- 11573564
TI  - Diclofenac induced renal dysfunction presenting as cardiac arrhythmia.
AB  - A fifty year old male presented on the sixteenth post-operative day after leg
      surgery with abdominal pain and distension, difficulty to breathe and oliguria.
      He had bradycardia and hypotension. Electrocardiography (ECG) revealed junctional
      rhythm and there was biochemical evidence of hyperkalemia. This was attributed to
      non-steroidal anti inflammatory drug diclofenac sodium induced renal dysfunction.

PMID- 11573565
TI  - Cerebral venous thrombosis in a patient of paroxysmal nocturnal haemoglobinuria
      following aplastic anaemia.
AB  - A young lady who had aplastic anaemia presented for cerebral venous thrombosis
      after five years of follow up. She was diagnosed to have paroxysmal nocturnal
      haemoglobinuria. She had received immunosuppressive therapy with
      methylprednisolone, cyclosporine-A, anti-lymphocyte globulin, danazol and
      pregnenolone. The relation between aplastic anaemia, paroxysmal nocturnal
      haemoglobinuria and cerebral venous thrombosis is discussed. The role of
      immunosuppressive therapy for aplastic anaemia in causation of paroxysmal
      nocturnal haemoglobinuria is reviewed.

PMID- 11573566
TI  - Acute disseminated encephalomyelitis--another cause of post malaria cerebellar
      ataxia.
AB  - The aetio-pathogenesis of delayed onset cerebellar ataxia following Plasmodium
      falciparum malaria is uncertain. An autoimmune demyelinating pathology has been
      suspected though not yet definitively substantiated. In the present communication
      we report a case of delayed onset cerebellar ataxia following acute falciparum
      malaria, where magnetic resonance imaging revealed demyelinating lesions in the
      pons and cerebellar peduncles which disappeared after resolution of symptoms.

PMID- 11573567
TI  - Isolated tubercular splenic abscess.
AB  - Splenic abscess due to tuberculosis is extremely rare in immunocompetent
      individuals. We report a case of tubercular splenic abscess (TSA) in an
      immunocompetent individual for its rarity.

PMID- 11573568
TI  - Well-differentiated inflammatory liposarcoma presenting as pyrexia of unknown
      origin.
AB  - Liposarcomas have diverse histological appearance and clinical manifestations.
      Well-differentiated inflammatory liposarcoma is an uncommon sub-type, which often
      causes diagnostic difficulty. We report here a young female patient who presented
      with prolonged pyrexia and sub-diaphragmatic mass and was detected to have this
      uncommon soft tissue sarcoma on laparotomy.

PMID- 11573569
TI  - Recurrent strokes--an interesting pedigree.

PMID- 11573570
TI  - Recurrent pyogenic meningitis in a case of transethmoid encephalocele.

PMID- 11573571
TI  - First unprovoked seizure--to treat or not to treat?

PMID- 11573573
TI  - Lightning injury with survival.

PMID- 11573572
TI  - Self injection of organophosphorous insecticide.

PMID- 11573574
TI  - Management strategies in silent myocardial ischaemia.

PMID- 11573575
TI  - Detection of resistance to isoniazid in clinical isolates of Mycobacterium
      tuberculosis by molecular techniques.

PMID- 11573576
TI  - Paralytic rabies following leopard bite.

PMID- 11573577
TI  - Circulating volume and clinical assessment of the circulation.

PMID- 11573578
TI  - A momentary pause...

PMID- 11573579
TI  - Is it safe to artificially ventilate a paralysed patient through the laryngeal
      mask? The jury is still out.

PMID- 11573580
TI  - Clinical evaluation of circulating blood volume in critically ill patients-
      contribution of a clinical scoring system.
AB  - The circulating blood volume (CBV) of critically ill patients may be difficult to
      estimate on the basis of history and physical examination. The aim of this study
      was to evaluate the ability of seven clinical signs and central venous pressure
      (CVP) to predict CBV in critically ill patients; CBV was evaluated with the
      [125I]human serum albumin technique. A scoring system was constructed using a
      combination of independence Bayes method and logistic regression. Sixty-eight
      patients constituted a 'model development' sample and 30 patients a validation
      sample. Thirty-six patients (53%) in the model development sample were found to
      have a low CBV (measured CBV at least 10% lower than the predicted mean normal
      CBV). Neither the haemodynamic variables monitored in ICU, nor the spot urinary
      sodium concentrations were different between patients with and without a low CBV.
      Individually, none of the clinical signs tested have a good positive or negative
      predictive value. For CVP, only extreme values seem to have clinical
      significance. To construct the score, the signs tested were ranked according to
      their discriminating efficacy. The probability of a low CBV was obtained by
      adding the weights of each sign tested and converting the score obtained into a
      probability. On a validation sample of 30 patients, the predictions are reliable
      as assessed by Z statistics ranging between -2 and +2. Our results suggest that:
      (1) individually, no clinical sign presented a clinical useful predictive value;
      and (2) a clinical scoring system may be helpful for the evaluation of CBV in
      critically ill patients.

PMID- 11573582
TI  - Monitoring level of sedation with bispectral EEG analysis: comparison between
      hypothermic and normothermic cardiopulmonary bypass.
AB  - The level of sedation of 28 patients undergoing elective coronary artery bypass
      grafting with fentanyl-propofol anaesthesia was monitored with bispectral
      analysis (BIS), spectral edge frequency, and band power of the
      electroencephalogram. Fourteen patients underwent hypothermic cardiopulmonary
      bypass (CPB) (32 degrees C, group H), and 14 normothermic CPB (group N). The
      level of sedation was measured with Observer's Assessment of Alertness/Sedation
      Score and with Ramsay Sedation Score. BIS was the only EEG measurement that
      paralleled the clinical course of the patients' sedation level. Values (median,
      95% confidence intervals (CI)) changed significantly over time in both groups
      (P<0.0001). In group H, BIS decreased from 97 (95, 99) the day before surgery to
      48 (44, 52) after tracheal intubation, to 46 (41, 52) before going off CPB, to 91
      (85, 97) immediately before extubation. In group N, values were 93 (91, 97) the
      day before surgery, 53 (47, 59) after tracheal intubation, 48 (43, 53) before
      going off CPB, and 90 (84, 96) before extubation. During CPB, BIS values were
      significantly different between the two groups. Group H had a median of 41 (95%
      CI, 39, 42), and group N had a median of 49 (95% CI, 48, 51, P<0.0001). Peak
      values of all other processed EEG parameters during anaesthesia and surgery
      overlapped with values from the day before, when patients had no sedating
      medication, and these values did not correlate to the patients' course of
      sedation during the study. There was no explicit recall of the surgery in either
      group. During the phases of anaesthesia and surgery without CPB, the progression
      of BIS levels was comparable with previously published data for non-cardiac
      surgery. During normothermic CPB, the highest BIS values were close to values
      representing insufficient depth of sedation. It remains to be elucidated whether
      the much lower BIS values in the hypothermic group were solely a result of brain
      cooling or if increased serum propofol concentrations, because of slowed
      pharmacodynamics during hypothermia, also contributed.

PMID- 11573581
TI  - Recovery after remifentanil and sufentanil for analgesia and sedation of
      mechanically ventilated patients after trauma or major surgery.
AB  - We investigated the analgesic effect and the neurological recovery time after
      administration of remifentanil in mechanically ventilated patients in an
      intensive care unit. Twenty patients, after trauma or major surgery with no
      intracranial pathology, were randomized to receive either remifentanil/propofol
      (n=10) or sufentanil/propofol (n=10). A sedation score and a simplified pain
      score were used to assess adequate sedation and analgesia. Medication was
      temporarily stopped after 24 h. Immediately before and 10 and 30 min after, the
      degree of sedation and pain score were evaluated. Adequate analgesia and sedation
      was achieved with remifentanil 10.6 microg kg(-1) h(-1) and propofol 2.1 mg kg(
      1) h(-1), or sufentanil 0.5 microg kg(-1) h(-1) and propofol 1.3 mg kg(-1) h(-1).
      The difference in propofol dose between groups was significant. Ten minutes after
      terminating the medication, the degree of sedation decreased significantly after
      remifentanil and all patients could follow simple commands. During the following
      20 min, all patients with remifentanil emerged from sedation and complained of
      considerable pain. By contrast, in the sufentanil group, only six (7) responded
      to commands after 10 (30) min and their pain score remained essentially unchanged
      during the 30-min observation period. We conclude that, in contrast to
      sufentanil, remifentanil facilitates rapid emergence from analgesia and sedation,
      allowing a clinical neurological examination within 10-30 min in mechanically
      ventilated patients with no intracranial pathology.

PMID- 11573583
TI  - Inspiratory timing during anaesthesia: a model of cardioventilatory coupling.
AB  - We describe a simple model of cardioventilatory coupling in which a hypothetical
      inspiratory pacemaker is stimulated by a signal related to cardiac action. At
      suitable values for the control variables (cardiac signal magnitude, heart rate,
      inspiratory pacemaker rate and inspiratory rate variability), the model was found
      to: (1) replicate all clinically described patterns of coupling; (2) predict
      variations in these described patterns and new patterns which were subsequently
      found in clinical time series; (3) simulate variations in clinically observed
      breathing frequency variations associated with each coupling pattern; (4)
      simulate the clinically observed distribution of coupling patterns between heart
      rate and breathing frequency; (5) explain the invariability of coupling below a
      critical heart rate/breathing frequency ratio; and (6) simulate the changes in
      breathing frequency and transitions between coupling patterns from the heart rate
      time series of human subjects. Although cardioventilatory coupling causes complex
      breathing rate irregularities during anaesthesia, these are readily explained by
      three variables, heart rate, intrinsic breathing frequency, and the strength of
      their interaction. This simple model, along with clinical observations of
      cardioventilatory coupling may provide a useful non-invasive method to study the
      respiratory central pattern generator.

PMID- 11573584
TI  - Survey of cancellation rate of hypertensive patients undergoing anaesthesia and
      elective surgery.
AB  - Hypertension is the commonest avoidable medical indication for postponing
      anaesthesia and surgery. There are no universally accepted guidelines stating the
      arterial pressure values at which anaesthesia should be postponed. The aim of
      this study was to determine the extent of variation across the South-West region
      of the UK in the anaesthetic management of patients presenting with stage 2 or
      stage 3 hypertension. Each anaesthetist in the region was sent a questionnaire
      with five imaginary case histories of patients with stage 2 or stage 3
      hypertension. They were asked if they would be prepared to provide anaesthesia
      for each patient. The response rate was 58%. We found great variability between
      anaesthetists as to which patients would be cancelled. Departmental protocols may
      aid general practitioners and surgeons in the preparation of patients for
      surgery, but such protocols may be difficult to agree in the light of such a wide
      variation in practice.

PMID- 11573585
TI  - Oesophageal Doppler monitoring overestimates cardiac output during lumbar
      epidural anaesthesia.
AB  - Oesophageal Doppler monitoring (ODM) has been advocated as a non-invasive means
      of measuring cardiac output (CO). However, its reliance upon blood flow
      measurement in the descending aorta to estimate CO is susceptible to error if
      blood flow is redistributed between the upper and lower body. We hypothesize that
      lumbar epidural anesthesia (LEA), which causes blood flow redistribution, causes
      errors in CO estimates. We compared ODM with thermodilution (TD) measurements in
      fourteen patients under general anaesthesia for radical prostatectomy, who had
      received an epidural catheter at the intervertebral level L2-L3. Coupled
      measurements of CO by means of the TD and ODM techniques were performed at
      baseline (general anaesthetic only) and after epidural administration of 10 ml of
      0.25% bupivacaine. The two methods were compared using Bland-Altman analysis:
      before LEA there was a bias of -0.89 litre min(-1) with limits of agreement
      ranging between -2.67 and +0.88 litre min(-1). Following lumbar sympathetic
      block, bias became positive (+0.55 litre min(-1)) and limits of agreement
      increased to -3.21 and +4.30 litre min(-1). ODM measured a greater increase in CO
      after LEA (delta=+1.71 (1.19) litre min(-1) (mean (SD)) compared with TD
      (delta=+0.51 (0.70) litre min(-1)). We conclude that following LEA, measurements
      with the Oesophageal Doppler Monitor II overestimate CO and show unacceptably
      high variability. Blood flow redistribution may limit the value of ODM.

PMID- 11573586
TI  - The lumbar epidural space in pregnancy: visualization by ultrasonography.
AB  - Epidural anaesthesia is an important analgesia technique for obstetric delivery.
      During pregnancy, however, obesity and oedema frequently obscure anatomical
      landmarks. Using ultrasonography, we investigated the influence of these changes
      on spinal and epidural anatomy. We examined 53 pregnant women who were to receive
      epidural block for vaginal delivery or Caesarean section. The first ultrasound
      imaging was performed immediately before epidural puncture; the follow-up scan
      was done 9 months later. The ultrasound scan of the spinal column was performed
      at the L3/4 interspace in transverse and longitudinal planes, using a Sonoace
      6000 ultrasonograph (Kretz, Marl, Germany) equipped with a 5.0-MHz curved array
      probe. We measured two distances from the skin to the epidural space: the minimum
      (perpendicular) and the maximum (oblique) needle trajectory. The quality of
      ultrasonic depiction was analysed by a numerical scoring system. An average
      weight reduction of 12.5 kg had occurred by the follow-up examination. During
      pregnancy, the optimum puncture site available on the skin for epidural space
      cannulation was smaller, the soft-tissue channel between the spinal processes was
      narrower, and the skin-epidural space distance was greater. The epidural space
      was narrower and deformed by the tissue changes. The visibility of the ligamentum
      flavum, of the dura mater and of the epidural space decreased significantly
      during pregnancy. Nevertheless, ultrasonography offered useful pre-puncture
      information. Thus far, palpation has been the only available technique to
      facilitate epidural puncture. Ultrasound imaging enabled us to assess the
      structures to be perforated. We anticipate that this technique will become
      valuable clinically.

PMID- 11573587
TI  - Spinal anaesthesia for Caesarean section with bupivacaine 5 mg ml(-1) in glucose
      8 or 80 mg ml(-1).
AB  - The standard spinal preparation of bupivacaine contains a high concentration of
      glucose (80 mg ml(-1)). However, the addition of only a small amount of glucose
      (8 mg ml(-1)) to plain solutions of bupivacaine results in a solution which,
      although no more than marginally hyperbaric, produces a more predictable block
      when used for spinal anaesthesia in non-pregnant patients. However, bupivacaine 5
      mg ml(-1) in glucose 8 mg ml(-1) has a density [1.00164 (SD 0.00008) at 37
      degrees C] which is relatively greater than that of the cerebrospinal fluid (CSF)
      of the pregnant patient at term (1.0003 at 37 degrees C) because CSF density
      decreases during pregnancy. Therefore, a double-blind, randomized, controlled
      study was carried out to compare intrathecal bupivacaine (glucose 8 mg ml(-1))
      with bupivacaine (glucose 80 mg ml(-1)) in 40 pregnant patients at term. Although
      there was no difference between groups in onset of sensory block, dose of
      ephedrine or patient satisfaction, patients receiving bupivacaine (5 mg ml(-1))
      with glucose (8 mg ml(-1)) had persistently higher sensory blocks between 60 and
      120 min after intrathecal injection, suggesting that the spread of spinal
      solutions in the pregnant patient at term is not dependent on density.

PMID- 11573588
TI  - Does prior administration of enoxaparin influence the effects of levobupivacaine
      on blood clotting? Assessment using the Thrombelastograph.
AB  - The low molecular weight heparin, enoxaparin (by inhibition of factors Xa and
      IIa) and amide local anaesthetics (by altering platelet function) exert anti
      clotting effects. Although these agents are often used in combination during the
      perioperative period, their potential interactive effect on clotting has not been
      defined. Blood from 10 ASA I-II patients who received enoxaparin 0.5 mg kg(-1)
      s.c. was studied using a Thrombelastograph (TEG) either alone or in combination
      with levobupivacaine (2.5 mg ml(-1) or 2.5 microg ml(-1)) or saline (50%
      dilution). In blood from patients who had received enoxaparin 0.5 mg kg(-1) s.c.
      12 h previously, levobupivacaine 2.5 mg ml(-1) (but not 2.5 microg ml(-1))
      produced significant changes in TEG clotting parameters (mean (SD) 15.7 (4.8) mm,
      29.6 (25.6) mm, 34.4 (14.6) mm, 34.3 (12.2) degrees compared with control values
      of 6.1 (1.3) mm, 2.5 (0.5) mm, 63.5 (6.4) mm and 74.1 (2.9) degrees for r, K, MA,
      and alpha angle respectively).

PMID- 11573589
TI  - Infusion of amino acid enriched solution hastens recovery from neuromuscular
      block caused by vecuronium.
AB  - We investigated the effect of an amino acid infusion on neuromuscular block
      produced by vecuronium, and on rectal temperature and surface temperature over
      the adductor pollicis muscle. Sixty adult patients undergoing general anaesthesia
      were randomly divided into four groups of 15 patients each: amino acid (AA)-post
      tetanic count (PTC); AA-train-of-four (TOF); control (C)-PTC; or C-TOF group. In
      the AA-PTC and AA-TOF groups, after a bolus of vecuronium 0.1 mg kg(-1), a
      continuous infusion of an 18 amino acid enriched solution (AMIPAREN) was started
      at a rate of 166 kJ h(-1). In the C-PTC and C-TOF groups, normal saline was
      administered. Time from vecuronium to the return of the PTC in the AA-PTC group
      was significantly shorter than in the C-PTC group (mean (SD), 13.3 (4.5) versus
      18.0 (5.6) min, P<0.05). Times to return of T1, T2, T3, and T4 (first, second,
      third, and fourth twitch of TOF) in the AA-TOF group were significantly shorter
      than in the C-TOF group (21.1 (4.5) versus 28.0 (8.2) min for T1, P<0.05). PTC in
      the AA-PTC group was significantly greater than in the C-PTC group; 25-35 min
      after administration of vecuronium (P<0.05). T1/T0 and T4/T1 in the AA-TOF group
      were significantly higher than in the C-TOF group, 40-120 and 50-120 min after
      vecuronium respectively (P<0.05). Rectal temperature and surface temperature over
      the adductor pollicis muscle in the AA-PTC and AA-TOF groups were significantly
      higher than in the control groups 50-120 and 100-120 min after vecuronium
      respectively (P<0.05). Infusion of amino acid enriched solution hastens recovery
      from neuromuscular block.

PMID- 11573590
TI  - What can be expected from risk scores for predicting postoperative nausea and
      vomiting?
AB  - Several risk scores have been developed to calculate the probability of
      postoperative nausea and vomiting (PONV). However, the power to discriminate
      which individual will suffer from PONV is still limited. Thus, we wondered how
      the number of predictors in a score affects the discriminating power and how the
      characteristics of a population--which is needed to measure the power of a score-
      may affect the results. For ethical reasons and to be independent from centre
      specific populations, we developed a computer model to simulate virtual
      populations. Four populations were created according to number, frequency, and
      odds ratio of predictors. Population I: parameters were derived from a previously
      published paper to verify whether calculated and reported values are in
      accordance. Population II: a gynaecological population was created to investigate
      the impact of the study setting. Populations III and IV: to meet ideal
      assumptions a model with up to seven predictors with an odds ratio of 2 and 3 was
      tested, respectively. The discriminating power of a risk score was measured by
      the area under a receiver operating characteristic curve (AUC) and an increase of
      more than 0.025 per predictor was considered to be clinically relevant. The AUC
      of population I was similar to those reported in clinical investigations (0.72).
      The study setting had a considerable impact on the discriminating power since the
      AUC decreased to 0.65 in a gynaecological setting. The AUC with the 'idealized'
      populations III and IV was at best in the range of 0.7-0.8. The inclusion of more
      than five predictors did not lead to a clinically relevant improvement. The
      currently available simplified risk scores (with four or five predictors) are
      useful both as a method to estimate individual risk of PONV and as a method for
      comparing groups of patients for antiemetic trials. They are also superior to
      single predictor models which are just using the patients' history of PONV or
      female gender alone. However, our analysis suggests that the power to
      discriminate which indvidual will suffer from PONV will remain imperfect, even
      when more predictors are considered.

PMID- 11573591
TI  - Downward movement of syringe pumps reduces syringe output.
AB  - We studied how lowering a syringe pump and changing the outflow pressure could
      affect syringe pump output. We experimentally reduced the height of three
      different syringe pump systems by 80 cm (adult setting) or 130 cm (neonatal
      setting), as can happen clinically, using five flow rates. We measured the time
      of backward flow, no flow and the total time without flow. An exponential
      negative correlation was present between infusion rate and time without flow
      (r2=0.809 to 0.972, P<0.01). Minimum flow rates of 4.4 and 2.6 ml h(-1)
      respectively were calculated to give 60 and 120 s without infusion. The
      compliance of the different syringe pumps and their infusion systems was linearly
      correlated with the effective time without infusion (r2=0.863, P<0.05). We
      conclude that the height of the syringe pumps should not be changed during
      transportation. If vertical movement of the syringe pump is necessary, the drugs
      should be diluted so that the flow rate is at least 5 ml h(-1).

PMID- 11573592
TI  - Influence of sepsis on sevoflurane minimum alveolar concentration in a porcine
      model.
AB  - Sevoflurane is widely used in anaesthetic protocols for patients undergoing
      surgical procedures. However, there are no reports on the influence of sepsis on
      minimum alveolar concentration of sevoflurane (MAC(SEV)) in animals or in humans.
      The aim of this study was to test the hypothesis that sepsis could alter the
      MAC(SEV) in a normotensive septic pig model. Twenty young, healthy pigs were
      used. After they had received 10 mg kg(-1) of ketamine i.m. for premedication,
      anaesthesia was established with propofol 3 mg kg(-1) and the trachea was
      intubated. Sevoflurane was used as the sole anaesthetic agent. Baseline
      haemodynamic recording included electrocardiography, carotid artery blood
      pressure and a pulmonary thermodilution catheter. Baseline MAC(SEV) in each pig
      was evaluated by pinching with a haemostat applied for 1 min to a rear dewclaw.
      MAC(SEV) was determined using incremental changes in sevoflurane concentration
      until purposeful movement appeared. Pigs were assigned randomly to two groups:
      the saline group (n = 10) received a 1-h i.v. infusion of sterile saline solution
      while the sepsis group (n = 10) received a 1-h i.v. infusion of live Pseudomonas
      aeruginosa. Epinephrine and hydroxyethylstarch were used to maintain normotensive
      and normovolemic haemodynamic status. In both groups, MAC(SEV) was evaluated 5 h
      after infusion. Significant increases in mean artery pulmonary pressure, filling,
      epinephrine and vascular pulmonary resistances occurred in the sepsis group.
      MAC(SEV) for the saline group was 2.4% [95% confidence interval (CI) 2.1-2.55%]
      and the MAC(SEV) for the sepsis group was 1.35% (95% CI 1.2-1.45%, P<0.05). These
      data indicate that MAC(SEV) is significantly decreased in this normotensive
      septic pig model.

PMID- 11573593
TI  - Halothane potentiates the effect of methamphetamine and nomifensine on
      extracellular dopamine levels in rat striatum: a microdialysis study.
AB  - Brain microdialysis was used to study the in vivo release and metabolism of
      dopamine (DA) in the rat striatum during halothane anaesthesia. Concentrations
      were measured in microdialysates collected every 20 min and applied directly to
      an on-line high-performance liquid chromatograph. Halothane was administered at
      concentrations of 0.5, 1.0, 1.5 and 2.0%. In another series of experiments, rats
      were treated intraperitoneally or locally with methamphetamine, a drug of abuse,
      or with nomifensine, a dopamine uptake blocker and antidepressant, in combination
      with 0.5 or 1.5% halothane. Halothane anaesthesia did not affect the dialysate
      (extracellular) concentration of DA at 2.0%. By contrast, the concentrations of
      DA metabolites [3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC)
      and homovanillic acid (HVA)] increased during inhaled halothane anaesthesia in a
      dose-dependent manner and recovered after anaesthesia. Halothane potentiated the
      ability of methamphetamine to increase the extracellular concentration of DA when
      administered systemically, whereas only a small increase in DA accumulation was
      seen when methamphetamine was administered locally via the perfusate. Similarly,
      the increase in extracellular DA was accentuated by systemic nomifensine during
      halothane anaesthesia, but no obvious enhancement was observed when it was
      applied locally. It has been shown that the neurotoxic effect of methamphetamine
      is mediated by the suboxidation of DA released from the cytoplasm into the
      extracellular space and transformed into highly reactive free radicals. On the
      basis of our results, it is suggested that care should be exercised when
      halothane anaesthesia is used in patients abusing phenylethylamines
      (amphetamines) or being treated with DA uptake blockers (nomifensine).

PMID- 11573594
TI  - Lidocaine reduces ischaemic but not reperfusion injury in isolated rat heart.
AB  - The local anaesthetic lidocaine protects the myocardium in ischaemia-reperfusion
      situations. It is not known if this is the consequence of an anti-ischaemic
      effect or an effect on reperfusion injury. Therefore, we investigated the effect
      of two concentrations of lidocaine on myocardial ischaemia-reperfusion injury and
      on reperfusion injury alone. We used an isolated rat heart model where heart
      rate, ventricular volume and coronary flow were kept constant. Hearts underwent
      45 min of low-flow ischaemia followed by 90 min reperfusion. Two groups received
      lidocaine 1.7 or 17 microg ml(-1) starting 5 min before the onset of reperfusion.
      In two additional groups, lidocaine infusion started 5 min before low-flow
      ischaemia. In all groups, lidocaine administration was stopped after 15 min of
      reperfusion. One group served as an untreated control (n=11 in each group). Left
      ventricular developed pressure (LVDP) and total creatine kinase release (CKR)
      were measured. Lidocaine administration during ischaemia and reperfusion led to
      an improved recovery of LVDP during reperfusion (1.7 microg ml(-1), 54 (SEM 10)
      mm Hg; 17 microg ml(-1), 71 (9) mm Hg at 30 min of reperfusion; both
      significantly different from control (21 (4) mm Hg) (P<0.05)) and a reduced CKR
      (1.7 microg ml(-1), 79 (13) IU; 17 microg ml(-1), 52 (8) IU at 30 min of
      reperfusion; both significantly different from control (130 (8) IU (P<0.05)).
      Lidocaine given during early reperfusion only, affected neither LVDP during
      reperfusion (1.7 microg ml(-1), 19 (6) mm Hg (P=1.0); 17 microg ml(-1), 36 (8) mm
      Hg (P=0.46)) nor CKR (156 (21) IU (P=0.50) and 106 (14) IU (P=0.57)). We conclude
      that lidocaine protects the myocardium against ischaemic but not against
      reperfusion injury in the isolated rat heart.

PMID- 11573595
TI  - Propofol inhibits FMLP-stimulated phosphorylation of p42 mitogen-activated
      protein kinase and chemotaxis in human neutrophils.
AB  - Propofol is used in the peri-operative setting and may affect some neutrophil
      functions. The effects of propofol on the function and intracellular signal
      transduction systems of neutrophils is controversial. Mitogen-activated protein
      kinase families (MAPKs) are members of the intracellular signal-transducing
      systems in eukaryotes. MAPKs have been shown to be involved in neutrophil
      chemotaxis by the use of PD98059, the specific inhibitor of MAPK/ERK kinase
      (MEK). The effects of propofol in dimethyl sulfoxide on phosphorylation of MAPKs
      and chemotaxis were investigated in human neutrophils. Isolated neutrophils (2 x
      10(7) cells per ml) from healthy volunteers were incubated with propofol (2-500
      microM) and stimulated by N-formyl-L-methionyl-phenylalanine (FMLP) (100 nM). The
      effects of propofol on the phosphorylation of p44/42 MAPK were investigated by
      immunoblotting. The effects of FMLP (1 microM) on chemotaxis were investigated
      with the under-agarose method. The phosphorylation of p42 MAPK and chemotaxis
      stimulated by FMLP were both inhibited by propofol at clinically relevant
      concentrations (> or = 10 and > or = 20 microM respectively). PD98059 (50 microM)
      also inhibited chemotaxis stimulated by FMLP, suggesting the involvement of p42
      MAPK in the response. Propofol might therefore inhibit human neutrophil
      chemotaxis, at least in part, by suppressing the p44/42 MAPK pathway.

PMID- 11573596
TI  - Perioperative bradycardia and asystole: relationship to vasovagal syncope and the
      Bezold-Jarisch reflex.
AB  - Reflex cardiovascular depression with vasodilation and bradycardia has been
      variously termed vasovagal syncope, the Bezold-Jarisch reflex and
      neurocardiogenic syncope. The circulatory response changes from the normal
      maintenance of arterial pressure, to parasympathetic activation and sympathetic
      inhibition, causing hypotension. This change is triggered by reduced cardiac
      venous return as well as through affective mechanisms such as pain or fear. It is
      probably mediated in part via afferent nerves from the heart, but also by various
      non-cardiac baroreceptors which may become paradoxically active. This response
      may occur during regional anaesthesia, haemorrhage or supine inferior vena cava
      compression in pregnancy; these factors are additive when combined. In these
      circumstances hypotension may be more severe than that caused by bradycardia
      alone, because of unappreciated vasodilation. Treatment includes the restoration
      of venous return and correction of absolute blood volume deficits. Ephedrine is
      the most logical choice of single drug to correct the changes because of its
      combined action on the heart and peripheral blood vessels. Epinephrine must be
      used early in established cardiac arrest, especially after high regional
      anaesthesia.

PMID- 11573597
TI  - Gastric residual volume in children: a study comparing efficiency of erythromycin
      and metoclopramide as prokinetic agents.
AB  - Metoclopramide may be used to stimulate gastric emptying when anaesthetizing
      children for emergency operations. Unfortunately, metoclopramide is associated
      with extrapyramidal side effects. Erythromycin, a motilin receptor agonist, is a
      prokinetic agent but its use has been little investigated in children. This
      randomized double-blind study compared the effects of premedication with oral
      metoclopramide 0.15 mg kg(-1) or erythromycin 1 mg kg(-1) on gastric emptying in
      80 children undergoing tonsillectomy. Pre-operative fluids, premedication and
      anaesthetic technique were standardized and gastric volume was measured with an
      orogastric tube. Post-operative nausea and vomiting was recorded. Metoclopramide
      and erythromycin produced similar gastric volumes (0.29 and 0.24 ml kg(-1)) and
      there was no difference in post-operative vomiting. In the erythromycin group
      there were more patients with negative aspirates (45.9%) than in the
      metoclopramide group (35.1%), but the difference was not statistically
      significant. These results indicate that erythromycin may be as effective as
      metoclopramide as a prokinetic agent.

PMID- 11573598
TI  - Effect of intravenous magnesium on pain and secondary hyperalgesia associated
      with the heat/capsaicin sensitization model in healthy volunteers.
AB  - We investigated the effects of i.v. magnesium on secondary hyperalgesia following
      heat/capsaicin stimulation in human volunteers. Twenty-five volunteers were
      included in this double blind, randomized, crossover study. Sensitization was
      induced in the volunteers, who were then subjected to either i.v. saline or
      magnesium sulphate. No analgesic or antihyperalgesic effect could be demonstrated
      in sensitized skin during infusion of magnesium. In contrast, painfulness of
      thermal stimulation was increased in normal skin. These results suggest that i.v.
      magnesium has no important analgesic effects in clinically relevant doses.

PMID- 11573599
TI  - Orally administered clonidine significantly reduces pain during injection of
      propofol.
AB  - We examined the analgesic effects of orally administered clonidine on pain
      induced by injection of propofol (Diprivan; 2,6-diisopropyl phenol). Female
      patients (n=81) were randomly allocated to one of two groups: oral clonidine (5.5
      microg kg(-1)) followed by i.v. propofol and a control group given placebo
      followed by i.v. propofol. The median pain score in the group receiving
      clonidine, using a four-point scale (0=no pain, 1=minimal pain, 2=moderate pain,
      3=severe pain) was 1 (0-2), significantly lower than in the control group [2 (1
      3), median (25-75 percentiles), P<0.001].

PMID- 11573600
TI  - Efficacy of varying concentrations of hyaluronidase in peribulbar anaesthesia.
AB  - We have compared the efficacy of adding varying concentrations of hyaluronidase
      to a standard mixture of 2% lidocaine and 1% ropivacaine to provide peribulbar
      anaesthesia for cataract surgery. We used (i) the time to adequate anaesthesia
      for surgery and (ii) ocular and eyelid movement scores at 8 min after block as
      clinical endpoints. Ninety patients were randomly allocated to receive 7-10 ml of
      equal volumes of 2% lidocaine and 1% ropivacaine without hyaluronidase or with
      hyaluronidase 15 IU ml(-1) or 150 IU ml(-1). Median time at which the block was
      adequate for surgery was 6 min in all groups (interquartile range 4-12 min).
      Median eyelid movement scores were similar in all groups, but the ocular movement
      scores at 8 min were significantly lower in the group which received
      hyaluronidase 150 IU ml(-1) than in the group not given hyaluronidase (P<0.03).
      There were no differences between groups in the incidence of minor complications.
      A high concentration of hyaluronidase resulted in a statistically significantly
      lower ocular movement score at 8 min; the clinical relevance of this finding is
      uncertain.

PMID- 11573601
TI  - Midazolam versus propofol for reducing contractility of fatigued canine
      diaphragm.
AB  - The effects of midazolam and propofol on the contractility of fatigued canine
      diaphragm were examined. Diaphragmatic fatigue was induced by intermittent
      supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied
      for 30 min. After fatigue had been induced, group I (n=10) received no study
      drug, group II (n=10) was given a propofol infusion (0.1 mg kg(-1) loading dose
      plus 1.5 mg kg(-1) h(-1) maintenance dose) and group III (n=10) was given a
      midazolam infusion (0.1 mg kg(-1) loading dose plus 0.1 mg kg(-1) h(-1)
      maintenance dose). Diaphragmatic contractility was assessed by measuring
      transdiaphragmatic pressure (Pdi). After the fatigue-inducing period in each
      group, Pdi at low-frequency (20 Hz) stimulation was lower than the baseline
      values (P<0.05), whereas no change in Pdi at high-frequency (100 Hz) stimulation
      was observed. In group II, Pdi at 20 Hz stimulation was lower than fatigued
      values (P<0.05); Pdi at 100 Hz stimulation did not change. In group III, Pdi at
      both stimulation frequencies was lower than fatigued values (P<0.05). Compared
      with group I, Pdi at 20 Hz stimulation was lower than fatigued values (P<0.05)
      during administration of the study drug in groups II and III. The decrease in Pdi
      was greater in group III than in group II (P<0.05). In conclusion, midazolam
      compared with propofol is associated with an inhibitory effect on contractility
      in the fatigued canine diaphragm.

PMID- 11573603
TI  - Respiratory failure after tracheal extubation in a patient with halo frame
      cervical spine immobilization--rescue therapy using the Combitube airway.
AB  - A 78-yr-old man, with halo frame cervical spine immobilization, suffered rapid
      respiratory deterioration after tracheal extubation in the intensive care unit.
      Control of the airway was difficult as bag-valve-mask ventilation was
      ineffective, tracheal intubation was known to be difficult from management of a
      previous episode of respiratory failure on the ward, and laryngeal mask insertion
      proved impossible. Rescue therapy using a Combitube airway is described and
      discussed.

PMID- 11573602
TI  - Xenon anaesthesia for laparoscopic cholecystectomy in a patient with
      Eisenmenger's syndrome.
AB  - There are few reports on anaesthesia for patients with Eisenmenger's syndrome
      requiring non-cardiac surgery and none of the use of xenon. We describe the use
      of xenon with a closed-circuit system in a patient with Eisenmenger's syndrome
      having a laparoscopic cholecystectomy.

PMID- 11573604
TI  - Intramuscular ketamine in a parturient in whom pre-operative intravenous access
      was not possible.
AB  - We describe the management of a 23-yr-old woman with extreme needle and mask
      phobia, presenting for an emergency Caesarean section for fetal distress. She
      also suffered from spina bifida cystica with no sensation from mid thigh.
      Regional anaesthesia, rapid sequence induction, and gaseous induction were not
      possible. She was managed successfully with i.m. ketamine followed by a more
      conventional anaesthetic technique.

PMID- 11573605
TI  - Cranial subdural haematoma after spinal anaesthesia.
AB  - Intracranial subdural haematoma is an exceptionally rare complication of spinal
      anaesthesia. A 20-yr-old male underwent appendicectomy under partial spinal and
      subsequent general anaesthesia. A week later, he presented with severe headache
      and vomiting not responding to bed rest and analgesia. Magnetic resonance imaging
      showed a small acute subdural haematoma in the right temporo-occipital region.
      The patient improved without surgical decompression. The pathogenesis of headache
      and subdural haematoma formation after dural puncture is discussed and the
      literature briefly reviewed. Severe and prolonged post-dural puncture headache
      should be regarded as a warning sign of an intracranial complication.

PMID- 11573606
TI  - Unilateral bronchospasm.

PMID- 11573607
TI  - Peri-operative beta-blockade.

PMID- 11573608
TI  - Production of human albumin solution: a continually developing colloid.

PMID- 11573609
TI  - Loss of consciousness following spinal anaesthesia for Caesarean section.

PMID- 11573610
TI  - Complete recovery of consciousness in a patient with decorticate rigidity
      following cardiac arrest after thoracic epidural injection.

PMID- 11573611
TI  - Topical anaesthesia for cataract surgery.

PMID- 11573612
TI  - Eye dimension and inadvertent perforation during eye blocks.

PMID- 11573613
TI  - Safe placement of central venous catheters.

PMID- 11573615
TI  - Fault after cannulation with a Y can.

PMID- 11573614
TI  - The time has come for non-interchangeability of spinal and epidural equipment
      with intravascular access ports.

PMID- 11573616
TI  - KISS and indices of pulmonary oxygen transfer.

PMID- 11573617
TI  - Continuous cardiac output by pulse contour analysis?

PMID- 11573618
TI  - Lessons from Stafford.

PMID- 11573619
TI  - Local anaesthesia for eye surgery-no room for complacency.

PMID- 11573620
TI  - Effect of changes in arterial-mixed venous oxygen content difference (C(a-v)O2)
      on indices of pulmonary oxygen transfer in a model ARDS lung.
AB  - Many indices are used to quantify pulmonary oxygen transfer. Indices that use
      only measurements from arterial blood and inspired gas assume a constant C(a
      v)O2. Though variations in C(a-v)O2 are recognized, indices such as PaO2/FIO2
      remain popular and are often considered the best measure of pulmonary oxygen
      transfer in critically ill patients. This study estimated the effect of within
      subject variations in C(a-v)O2 and FIO2 on venous admixture (Qs/Qt), the
      calculated oxygen content difference between end-capillary and arterial blood
      (Cc'O2-CaO2), the alveolar-arterial oxygen tension gradient (P(A-a)O2) and
      PaO2/FIO2, using a validated lung model of acute respiratory distress syndrome
      (ARDS). All four indices showed changes with FIO2 and C(a-v)O2, although the
      magnitude of changes in Qs/Qt was clinically unimportant (<2%). The other three
      indices showed larger variations that may potentially be misleading. At an FlO2
      of 0.7, PaO2 /FIO2 varied between 18 and 10 kPa and at an FIO2 of 0.9 the ratio
      varied between 22 and 8 kPa. These changes, which were unrelated to underlying
      lung pathology, are sufficiently large to result in misclassification on the gas
      exchange scale suggested by the American European Consensus Conference on ARDS.
      This study shows there is no reliable alternative to Qs/Qt to quantify pulmonary
      oxygen transfer in critically ill patients.

PMID- 11573621
TI  - Estimation of changes in cardiac output from the arterial blood pressure waveform
      in the upper limb.
AB  - We have developed a new pulse contour cardiac output (PulseCO) algorithm based on
      frequency analysis studies of the arterial system. PulseCO was compared with
      thermodilution cardiac output (TDCO) in 10 patients undergoing cardiac surgery.
      Results from one patient were unsuitable for analysis. In the remaining nine
      patients, 142 TDCO determinations were compared with PulseCO after logarithmic
      transformation and after being normalized by the initial cardiac output in each
      patient. Each determination was usually the average of three measurements. Least
      squares regression gave y = 0.77 x (r2 = 0.81) and the limits of agreement were
      from -26% to +21%. The accuracy of PulseCO in determining short-term changes in
      cardiac output was assessed by comparing the ratios of consecutive PulseCO
      determinations with the ratios of the corresponding, consecutive TDCO
      determinations. Least squares regression gave y = 0.71 x (r2 = 0.70) and the
      limits of agreement were from -21% to +25%. After phenylephrine had been given to
      five patients, PulseCO showed an increase in systemic vascular resistance
      consistent with the known pharmacological actions of the drug. The PulseCO
      algorithm was incorporated into a computer program that acquires arterial
      pressure data from an analogue-to-digital converter and displays beat-to-beat
      trend values.

PMID- 11573622
TI  - Transoesophageal echocardiography in cardiac and vascular surgery: implications
      and observer variability.
AB  - Transoesophageal echocardiography (TOE) has gained widespread acceptance among
      cardiac anaesthetists as a tool to facilitate peri-operative decision-making.
      This observational study analyses the impact of TOE and its inter-observer
      variability on intra-operative patient management during cardiac and major
      vascular surgery. From June 1996 to December 1998, standardized reports were
      obtained from 11 anaesthetists in 1891 adult cardiac and vascular surgery
      patients undergoing routine biplane or multiplane TOE. Inter-observer variability
      and the difference between variables of interest were tested using the chi
      squared test or factorial analysis of variance as appropriate. TOE examinations
      were performed before and after the operation; 1,673 (88.5%) patients underwent
      cardiopulmonary bypass (CPB), and 218 (11.5%) patients had surgery without CPB,
      including 42 (2.2%) coronary revascularizations. In 923 patients (49%), TOE
      provided additional information that influenced the patient's therapy. In 968
      patients (51%), TOE had only minor or no impact on clinical decision-making. In
      two patients (0.10%) the scheduled operation was not performed, and in another
      two patients the TOE examination led to major complications. Observer-dependent
      variables were: implications of TOE for intraoperative decision-making
      (P<0.0001), estimation of image quality (P < 0.0001), pre-operative left
      ventricular fractional area change (FAC) (P = 0.0026), difference between pre
      operative FAC and post-operative FAC (P = 0.033), and requests for supervision (P
      < 0.0001). There was no significant difference in the case mix between observers.
      TOE had an important impact on intraoperative patient management. Inter-observer
      variability was significant for several variables but not for the frequency of
      additional surgical procedures.

PMID- 11573623
TI  - Intercurrent drug therapy and perioperative cardiovascular mortality in elective
      and urgent/emergency surgical patientst.
AB  - The Oxford Record Linkage Study (ORLS; an epidemiological database) was used to
      examine relationships between intercurrent cardiovascular drug therapy and
      cardiac death within 30 days of elective or emergency/urgent surgery under
      general anaesthesia. Cases identified from the ORLS were paired with matched
      control patients. Clinical details were obtained from the patients' medical
      notes. In elective surgical patients, there was no effect of beta-adrenoceptor or
      calcium entry channel blockade, diuretics or digoxin on cardiac death after
      adjusting for confounding variables. Use of nitrates was associated with an odds
      ratio of 4.79 [95% confidence interval (CI) 1.01-22.72] for cardiac death after
      adjustment for confounding by a history of angina and residual age difference. In
      emergency/urgent patients, there were significant univariate associations with
      cardiac death for intercurrent use of angiotensin converting enzyme (ACE)
      inhibitors (odds ratio 1.18) and diuretics (odds ratio 4.95; 95% CI 1.82-13.46).
      However, neither maintained significance after adjustment for the confounding
      effect of cardiac failure. We conclude that, with the possible exception of the
      use of nitrates in elective surgical patients, chronic intercurrent drug
      treatment alone does not significantly affect the odds of cardiac death within 30
      days of surgery.

PMID- 11573624
TI  - The auditory evoked response as an awareness monitor during anaesthesia.
AB  - We investigated the relationship between the latency of the Nb wave of the
      auditory evoked response (AER) and periods of awareness during propofol
      anaesthesia. In the anaesthetic room before cardiac surgery the AER was recorded
      continuously in 14 patients. Awareness was measured by the ability of the patient
      to respond to command using the isolated forearm technique (IFT). The Nb
      latencies were shorter when the patients were able to respond than at loss of
      response (P<0.001). In six patients who repeated this transition from response to
      loss of response, there was a high and significant correlation between Nb
      latencies. None of the patients had any recollection of events after the initial
      induction of anaesthesia as measured by explicit and implicit memory tests. These
      results suggest that the Nb latency of the AER may represent an indication of
      awareness in individual patients, but wide inter-patient variability limits its
      practical usefulness. In addition, because no evidence of memory was
      demonstrated, even when patients were known to be awake, the relationship between
      AER and memory processing remains unclear.

PMID- 11573625
TI  - Ocular microtremor: a tool for measuring depth of anaesthesia?
AB  - Ocular microtremor (OMT) is a fine high frequency tremor of the eyes caused by
      extra-ocular muscle activity stimulated by impulses emanating in the brain stem.
      Several studies have shown that the frequency of this tremor is reduced in
      patients whose consciousness is reduced by anaesthesia or head injury. Therefore,
      OMT may possibly be used to determine depth of anaesthesia. Twenty-two unpre
      medicated subjects undergoing surgery with general anaesthesia were studied. OMT
      activity was measured at admission using the open eye piezoelectric strain gauge
      technique. Anaesthesia was induced with propofol using a target controlled
      infusion delivery system (Diprifusor). OMT activity was then recorded at
      predicted plasma propofol concentrations of 1, 2, 3 and 5 microg ml(-1). The
      patient's level of consciousness (response to command or stimulation) was
      assessed after each OMT measurement. OMT activity was reduced progressively at
      predicted plasma concentrations of propofol of I and 2 microg ml(-1) and then
      plateaued between 3 and 5 microg ml(-1). There was a significant difference
      between the last awake OMT recording and the first recording at loss of
      consciousness (P < 0.001). OMT recording holds promise as a practical indicator
      of the depth of anaesthesia.

PMID- 11573627
TI  - Antinociceptive properties of neurosteroids IV: pilot study demonstrating the
      analgesic effects of alphadolone administered orally to humans.
AB  - Fourteen patients scheduled for orthopaedic knee reconstruction surgery were
      enrolled in a prospective, double-blind, randomized study in which they received
      alphadolone (25-500 mg, n = 9) or placebo (lactose, n = 5) given orally 1 h after
      operation. All the subjects received a standardized general anaesthetic and the
      same type of surgery followed by physiotherapy using a continuous passive
      movement machine. Morphine was administered intravenously after operation by
      patient-controlled analgesia. Verbal rating and visual analogue scores assessed
      pain experiences for 6 h. Orally administered alphadolone up to 500 mg caused no
      increase in sedation, respiratory depression, nausea or vomiting. The experiences
      of these side-effects were all rated as none, mild or moderate. Orally
      administered alphadolone caused statistically significant reductions in morphine
      use and simultaneous highly significant reductions in pain scores. We conclude
      that alphadolone is a useful analgesic in humans when given by the oral route.

PMID- 11573626
TI  - Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of
      consciousness and bispectral index during propofol induction of anaesthesia.
AB  - The bispectral index (BIS) and a sedation score were used to determine and
      compare the effect of propofol in the presence of fentanyl, alfentanil,
      remifentanil and sufentanil. Seventy-five non-premedicated patients were assigned
      randomly into five groups (15 in each) to receive fentanyl, alfentanil,
      remifentanil, sufentanil or placebo. Opioids were administered using a target-con
      trolled infusion device, to obtain the following predicted effect-site
      concentrations: fentanyl, 1.5 ng ml(-1); alfentanil, 100 ng ml(-1); remifentanil,
      6 ng ml(-1); and sufentanil, 0.2 ng ml(-1). After this, a target-controlled
      infusion of propofol (Diprifusor) was started to increase concentration
      gradually, to achieve predicted effect-site concentrations of 1, 2, and 4 microg
      ml(-1). At baseline and at each successive target effect-site concentration of
      propofol, the BIS, sedation score and haemodynamic variables were recorded. At
      the moment of loss of consciousness (LOC), the BIS and the effect-site
      concentration of propofol were noted. The relationship between propofol effect
      site concentration and BIS was preserved with or without opioids. In the presence
      of an opioid, LOC occurred at a lower effect-site concentration of propofol and
      at a higher BIS50 (i.e. the BIS value associated with 50% probability of LOC),
      compared with placebo. Although clinically the hypnotic effect of propofol is
      enhanced by analgesic concentrations of mu-agonist opioids, the BIS does not show
      this increased hypnotic effect.

PMID- 11573628
TI  - Persistent back pain after spinal anaesthesia in the non-obstetric setting:
      incidence and predisposing factors.
AB  - We determined the incidence of persistent back pain (PBP) after non-obstetrical
      spinal anaesthesia (SPA) and investigated factors predisposing to such pain in a
      prospective 1 yr follow-up study in 245 patients undergoing elective general or
      trauma surgery (218 patients undergoing single SPA, 27 undergoing two to six
      SPAs). All patients received a first questionnaire 3 months after the last SPA,
      and those reporting PBP after 3 months were sent a second questionnaire I year
      after the operation. Variables were PBP before and within 5 days, at 3 months and
      I year after SPA, patient satisfaction with SPA, patient characteristics and
      technical data. Statistical analysis was by contingency tables with Fisher's
      exact test and an unpaired t-test with logistic regression (P < 0.001 after
      Bonferroni correction was taken as significant). The response rate in patients
      who had a single SPA was 56% (122/218). Twenty-three of these 122 patients
      (18.9%) complained of back pain before SPA compared with 12/122 (10.7%, P =
      0.0015) within 5 days after SPA. After 3 months, 15/122 patients (12.3%) reported
      PBP with 14 complaining of PBP before SPA (P < 0.0001), corresponding to an
      incidence of new PBP of 1/122 (0.8%). Multiple logistic regression revealed that
      pre-existing back pain was the only variable associated with PBP after 3 months
      (P < 0.0001). Patient characteristics and technical factors were not associated
      with PBP. Nine of the 15 patients with PBP after 3 months returned the second
      questionnaire: four still reported PBP (three of these had suffered from PBP
      before SPA). Despite PBP after 3 months, 13/15 patients said they would opt for
      SPA again. The response rate and results in patients who had had multiple SPAs
      were similiar to those who had had a single SPA.

PMID- 11573629
TI  - Cytochrome P4502B6 and 2C9 do not metabolize midazolam: kinetic analysis and
      inhibition study with monoclonal antibodies.
AB  - We determined the contribution of cytochrome P450 (CYP) isoforms to the
      metabolism of midazolam by kinetic analysis of human liver microsomes and CYP
      isoforms and by examining the effect of chemical inhibitors and monoclonal
      antibodies against CYP isoforms in vitro. Midazolam was metabolized to 1'
      hydroxymidazolam (1'-OH MDZ) by human liver microsomes with a Michaelis-Menten
      constant (Km) of 4.1 (1.0) (mean (SD)) micromol litre(-1) and a maximum rate of
      metabolism (Vmax) of 5.5 (1.1) nmol min(-1) mg protein(-1) (n = 6). Of the nine
      representative human liver CYP isoforms, CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1,
      3A4 and 3A5, three (CYP2B6, 3A4 and 3A5) showed midazolam 1'-hydroxylation
      activity, with Kms of 40.7, 1.7 and 3.0 micromol litre(-1), respectively, and
      Vmax values of 12.0, 3.3 and 13.2 nmol min(-1) nmol P450(-1), respectively (n =
      4). Midazolam 1'-hydroxylation activity of human liver microsomes correlated
      significantly with testosterone 6beta-hydroxylation activity, a marker of CYP3A
      activity (r2 = 0.77, P = 0.0001), but not with S-mephenytoin N-demethylation
      activity, a marker of CYP2B6 activity (r2 < 0.01, P = 0.84) (n = 11).
      Troleandomycin and orphenadrine, chemical inhibitors of CYP isoforms, inhibited
      the formation of 1'-OH MDZ by human liver microsomes. Monoclonal antibody against
      CYP3A4 inhibited the formation of 1'-OH MDZ by 79%, whereas monoclonal antibody
      against CYP2B6 had no effect on midazolam 1'-hydroxylation by human liver
      microsomes (n = 5). These results indicate that only CYP3A4, but not CYP2B6 or
      CYP2C, is involved in the metabolism of midazolam in vitro.

PMID- 11573630
TI  - Naloxone improves functional recovery of myocardial stunning in conscious dogs
      through its action on the central nervous system.
AB  - This study tests the hypothesis that naloxone, but not its quarternary salt,
      naloxone methiodide (which does not enter the central nervous system), improves
      recovery from myocardial stunning in conscious dogs. Twenty dogs were chronically
      instrumented for measurement of heart rate, left atrial, aortic and left
      ventricular pressure (LVP), LV dP x dtmax(-1) and myocardial wall thickening
      fraction (WTF). Regional myocardial blood flow was determined with coloured
      microspheres. Occluder around the left anterior descending artery (LAD) allowed
      induction of reversible LAD ischaemia. Each of the 20 dogs underwent two LAD
      ischaemic challenges. Experiments (performed on separate days, in crossover
      fashion) were: (i) 10 min of LAD occlusion after application of naloxone 63
      microg kg(-1) or naloxone methiodide 63 microg kg(-1) and (ii) occlusion without
      naloxone or naloxone methiodide. WTF was measured at baseline and until complete
      recovery occurred. LAD ischaemia significantly reduced LAD WTF with (mean (SD) 54
      (15)% lower than baseline) and without naloxone (55 (16)% lower than baseline),
      without significant haemodynamic differences. Between I to 30 min of reperfusion,
      WTF was significantly higher with naloxone (P < 0.05). There was no difference in
      WTF with or without naloxone methiodide. We conclude that naloxone improved
      recovery from myocardial stunning in conscious dogs, and that this was centrally
      mediated.

PMID- 11573631
TI  - Effects of sevoflurane on dopamine, glutamate and aspartate release in an in
      vitro model of cerebral ischaemia.
AB  - Release of excitatory amino acids and dopamine plays a central role in neuronal
      damage after cerebral ischaemia. In the present study, we used an in vitro model
      of ischaemia to investigate the effects of sevoflurane on dopamine, glutamate and
      aspartate efflux from rat corticostriatal slices. Slices were superfused with
      artificial cerebrospinal fluid at 34 degrees C and episodes of 'ischaemia' were
      mimicked by removal of oxygen and reduction in glucose concentration from 4 to 2
      mmol litre(-1) for < or = 30 min. Dopamine efflux was monitored in situ by
      voltammetry while glutamate and aspartate concentrations in samples of the
      superfusate were measured by HPLC with fluorescence detection. Neurotransmitter
      outflow from slices was measured in the absence or presence of sevoflurane (4%).
      After induction of ischaemia in control slices, there was a mean (SEM) delay of
      166 (7) s (n = 5) before sudden efflux of dopamine which reached a maximum
      extracellular concentration of 77.0 (15.2) micromol litre(-1). Sevoflurane (4%)
      reduced the rate of dopamine efflux during ischaemia (6.90 (1.5) and 4.73 (1.76)
      micromol litre(-1) s(-1) in controls and sevoflurane-treated slices,
      respectively; P<0.05), without affecting its onset or magnitude. Excitatory amino
      acid efflux was much slower. lschaemia-induced glutamate efflux had not reached
      maximum after 30 min of ischaemia. Basal (pre-ischaemic) glutamate and aspartate
      efflux per slice was 94.8 (24.8) and 69.3 (31.5) nmol litre(-1) superfusate (n =
      4) and was not significantly reduced by 4% sevoflurane. lschaemia greatly
      increased glutamate and aspartate efflux (to a maximum of 919 (244)% and 974
      (489)% of control, respectively). However, ischaemia-induced efflux of both
      glutamate and aspartate was significantly reduced by 4% sevoflurane (P < 0.001
      for glutamate, P < 0.01 for aspartate). In summary, sevoflurane may owe part of
      its reported neuroprotective effect to a reduction of ischaemia-induced efflux of
      excitatory amino acids and, to a lesser extent, dopamine.

PMID- 11573632
TI  - Neurofibromatosis: clinical presentations and anaesthetic implications.
AB  - The neurofibromatoses are autosomal dominant diseases that have widespread
      effects on ectodermal and mesodermal tissue. The commonest member of the group is
      neurofibromatosis type 1 (NF1) which varies in severity but which can affect all
      physiological systems. Neurofibromas are the characteristic lesions of the
      condition and not only occur in the neuraxis but may also be found in the
      oropharnyx and larynx; these may produce difficulties with laryngoscopy and
      tracheal intubation. Pulmonary pathology includes pulmonary fibrosis and cystic
      lung disease. The cardiovascular manifestations of NF1 include hypertension,
      which may be associated with phaeochromocytoma or renal artery stenosis.
      Neurofibromas may also affect the gastrointestinal tract and carcinoid tumours
      may be found in the duodenum. This review documents the aetiology and clinical
      manifestations of the neurofibromatoses and discusses their relevance to the
      anaesthetist.

PMID- 11573633
TI  - Intrapartum epidural catheter migration: a comparative study of three dressing
      applications.
AB  - We compared three types of catheter fixation application for their ability to
      minimize the incidence and magnitude of epidural catheter movement during labour.
      Patients were randomized to have their epidural catheter secured by a Tegaderm
      dressing (group T; n = 35), a Tegaderm dressing plus filter-shoulder fixation
      (group F; n = 39), or a Niko Epi-Fix dressing (group N; n = 37). The length of
      catheter visible at the patient's skin surface was recorded (to the nearest 0.5
      cm) after insertion and before removal; the difference was defined as 'catheter
      movement'. Outward movement of the catheter was greatest when a Niko Epi-Fix was
      used (P < 0.01). Concerning minimization of displacement of the epidural catheter
      per se, only a Tegaderm dressing with additional filter-shoulder fixation proved
      more effective than using a Niko Epi-Fix dressing (P < 0.05).

PMID- 11573634
TI  - Choice of opioid for initiation of combined spinal epidural analgesia in labour-
      fentanyl or diamorphine.
AB  - Sixty-two women requesting regional analgesia in labour were allocated to receive
      a 1.5 ml intrathecal injection as part of a combined spinal-epidural (CSE)
      analgesic technique. This contained either bupivacaine 2.5 mg plus fentanyl 25
      microg (group F) or bupivacaine 2.5 mg plus diamorphine 250 microg (group D).
      Times of analgesic onset and offset were recorded, motor and proprioceptive
      assessments made and side-effects noted. Analgesic onset was not significantly
      different between the groups (group F, 8.0 min; group D, 9.5 min; P = 0.3) but
      time to first top-up request was significantly longer in the diamorphine group
      (group F, 73 min; group D, 101 min; P = 0.003). Motor loss, assessed by the
      modified Bromage score, was statistically but not clinically greater in the
      fentanyl group (P = 0.01). Maternal hypotension, pruritus, proprioceptive loss,
      nausea and fetal bradycardia were rare and not severe, and their incidences did
      not differ between groups. No respiratory depression was observed after CSE. This
      use of diamorphine was not associated with increased side-effects compared with
      fentanyl/bupivacaine, and it has a longer duration of action.

PMID- 11573635
TI  - Small-dose selective spinal anaesthesia for short-duration outpatient
      gynaecological laparoscopy: recovery characteristics compared with propofol
      anaesthesia.
AB  - A randomized controlled trial compared recovery characteristics after selective
      spinal anaesthesia (SSA) or propofol general anaesthesia (GA) for short-duration
      outpatient laparoscopic surgery. Forty women were randomized to receive either
      SSA (1% lidocaine 10 mg, sufentanil 10 microg and sterile water 1.8 ml) or GA
      (propofol and nitrous oxide 50% in oxygen). Compared with the GA group, times to
      leaving the operating room, performing a straight leg raise, performing deep knee
      bends and achieving an Aldrete score >9 and the time in Phase II recovery were
      significantly shorter (P < 0.05) in the SSA group.

PMID- 11573636
TI  - Analgesic efficacy of tramadol 2 mg kg(-1) for paediatric day-case adenoidectomy.
AB  - We studied the analgesic efficacy of tramadol 2 mg kg(-1) for post-operative
      analgesia after day-case adenoidectomy in children aged 1-3 yr. Eighty children
      were allocated randomly to receive tramadol 2 mg kg(-1) i.v. or placebo
      immediately after induction of anaesthesia. Anaesthesia was induced with
      alfentanil 10 microg kg(-1) and propofol 4 mg kg(-1) followed by mivacurium 0.2
      mg kg(-1) for tracheal intubation. Anaesthesia was continued with sevoflurane in
      nitrous oxide and oxygen. All children were given ibuprofen rectally at
      approximately 10 mg kg(-1) before the start of surgery. Post-operative pain and
      recovery assessments were performed by a nurse blinded to the analgesic treatment
      using the Aldrete recovery score, the pain/discomfort scale and measurement of
      recovery times. Rescue medication (pethidine in increments of 5 mg i.v.) was
      administered according to the pain scores. A post-operative questionnaire was
      used to evaluate the need for analgesia at home up to 24 h after operation.
      Rescue analgesic at home was rectal or oral ibuprofen 125 mg. Children in the
      tramadol group required fewer pethidine doses than those in the placebo group (P
      = 0.014). Forty-five per cent of children receiving tramadol did not require post
      operative analgesia at all compared with 15% of children receiving placebo (P =
      0.003). Recovery times and the incidence of adverse effects were similar in the
      two groups in the recovery room and at home. The requirement for rectal ibuprofen
      at home did not differ between groups.

PMID- 11573637
TI  - Reduced haemostatic factor transfusion using heparinase-modified
      thrombelastography during cardiopulmonary bypass.
AB  - We set out to determine if the heparinase-modified thrombelastogram using
      anticoagulated blood from patients during cardiac surgery could guide treatment
      with haemostatic components. In 60 patients a simple algorithm predicted a
      possible 60-80% decrease in the use of haemostatic components. In a second
      series, 30 patients were allocated to receive components using this intra
      operative algorithm and 30 using clinical criteria and laboratory-based tests.
      Ten patients in the clinical group received a total of 16 units of fresh frozen
      plasma and nine platelet concentrates compared with five patients transfused with
      five units of fresh frozen plasma and one platelet concentrate in the algorithm
      group. Twelve-hour chest tube losses [algorithm group 470 (295-820) ml,
      clinically managed group 390 (240-820) ml (median, quartile values)] were not
      different between groups despite the threefold reduction in the use of
      haemostatic products, showing that intra-operative monitoring of coagulation in
      the anticoagulated patient can be used to guide treatment.

PMID- 11573639
TI  - Review of management of purpura fulminans and two case reports.
AB  - Purpura fulminans (PF) is a haemorrhagic condition usually associated with sepsis
      or previous infection. Features include tissue necrosis, small vessel thrombosis
      and disseminated intravascular coagulation. Gram-negative organisms are the
      commonest cause of the acute infectious type, which is often associated with
      multi-organ failure. An idiopathic variety, however, is often confined to the
      skin. The mortality rate has decreased with better treatment of secondary
      infections, supportive care and new treatments, but it remains a disabling
      condition often requiring major amputations. We describe two cases and review the
      various treatments for this condition.

PMID- 11573638
TI  - Circulating tetrahydrobiopterin concentrations in patients with septic shock.
AB  - Nitric oxide synthase requires tetrahydrobiopterin for its activity. In animal
      models of sepsis, changes in circulating tetrahydrobiopterin concentrations
      precede increases in nitrate. We measured plasma tetrahydrobiopterin and nitrate
      concentrations on three consecutive days in 10 patients with septic shock and 10
      critically ill control patients. Total nitrate concentration was measured after
      reduction of nitrite to nitrate. Tetrahydrobiopterin concentrations were measured
      using HPLC. The median (range) APACHE II score was 22 (13-27) in the patients
      with septic shock and 25 (7-28) in the control group. The nitrate concentration
      was significantly higher in patients with septic shock than in controls (P =
      0.01) on all days but did not change with time. Tetrahydrobiopterin
      concentrations were highest in the patients with septic shock on day 1 only (P =
      0.037). In the seven patients with renal failure, both nitrate and
      tetrahydrobiopterin concentrations tended to be higher than in the 13 patients
      without renal failure. The nitrate concentration correlated with
      tetrahydrobiopterin concentration on day 1 only (P = 0.05). In patients with
      septic shock, both tetrahydrobiopterin and total nitrate concentrations were
      higher than those in critically ill controls but were increased mainly in
      patients with renal failure. In summary, tetrahydrobiopterin concentration
      increases during septic shock, in line with increases in nitrate concentration.
      However, as for nitrate, concentrations

PMID- 11573640
TI  - Intra-operative and post-operative hypercapnia leading to delayed respiratory
      failure associated with transanal endoscopic microsurgery under general
      anaesthesia.
AB  - We present an unusual case of hypercapnia and surgical emphysema during transanal
      endoscopic microsurgery, which led to delayed post-operative ventilatory failure.
      The hypercapnia and surgical emphysema were secondary to rectal insufflation with
      carbon dioxide used to facilitate visualization and resection of a rectal tumour.
      Despite a return to wakefulness after surgery, the patient's level of
      consciousness deteriorated in the recovery area as a result of hypercapnia. The
      PaCO2 rose to 16.8 kPa because of absorption of carbon dioxide from the surgical
      emphysema. On close examination, surgical emphysema was identified in unusual
      areas, including the anterior abdominal wall, both loins, both groins and the
      left thigh. Reventilation was required until these unusual carbon dioxide stores
      had dissipated. We discuss the need for prolonged post-operative vigilance in
      patients with surgical emphysema secondary to carbon dioxide insufflation, and
      the risk of delayed ventilatory failure.

PMID- 11573641
TI  - Acute respiratory and metabolic acidosis induced by excessive muscle contraction
      during spinal evoked stimulation.
AB  - Spinal somatosensory evoked potentials (SSEPs) have been used to monitor spinal
      cord function during corrective scoliosis surgery. We report three cases in which
      direct epidural stimulation for measurement of SSEPs produced paraspinal muscle
      contraction, resulting in respiratory and metabolic acidosis. In two of the
      cases, SSEP-induced acidosis was observed even when only the first twitch of the
      train-of-four response was detectable after a second dose of muscle relaxant. In
      one of these two cases, the acidosis was abolished after a sufficient dose of
      vecuronium to ablate the twitch response. To prevent SSEP-induced respiratory and
      metabolic acidosis, we recommend that SSEPs should be measured only when profound
      neuromuscular blockade has been obtained.

PMID- 11573642
TI  - Phaeochromocytoma-recent progress in its management.

PMID- 11573643
TI  - Volatile anaesthetics and the atmosphere: an end to 'scavenging'?

PMID- 11573644
TI  - Hypoxaemia, platypnoea, orthodeoxia and right-to-left shunts.

PMID- 11573645
TI  - Hypoxaemia, platypnoea, orthodeoxia and right-to-left shunts.

PMID- 11573646
TI  - Acute right-to-left inter-atrial shunt.

PMID- 11573647
TI  - Peripheral nerve stimulation end-point for thoracic paravertebral block.

PMID- 11573648
TI  - Use of intravenous opioids to reduce airway irritation during induction of
      anaesthesia with desflurane.

PMID- 11573649
TI  - Overdose of ketoprofen could be dangerous.

PMID- 11573650
TI  - Extra cranial sources of S100B.

PMID- 11573651
TI  - The proseal LMA: preliminary data.

PMID- 11573652
TI  - Peri-operative beta-blockade: a useful treatment that should be greeted with
      cautious enthusiasm.

PMID- 11573653
TI  - Is peri-operative renal dysfunction of no consequence?

PMID- 11573654
TI  - A breakthrough in the genetic diagnosis of malignant hyperthermia.

PMID- 11573655
TI  - Haemodynamic and renal effects of intravenous enalaprilat during coronary artery
      bypass graft surgery in patients with ischaemic heart dysfunction.
AB  - Renal dysfunction occurring after open heart surgery is multifactorial in origin
      but activation of the renin-angiotensin system may have a prominent role.
      Fourteen patients with ischaemic heart dysfunction scheduled for elective
      coronary artery bypass graft (CABG) surgery were allocated to a treatment group
      [enalaprilat for 2 days; ACEI (angiotensin-converting enzyme inhibitor) group,
      n=7] or a control group (n=7). The cardiac index was significantly higher in ACEI
      treated patients than in the controls before and after cardiopulmonary bypass
      (CPB) (P<0.05) and on postoperative day 2 (P<0.05). The systemic vascular
      resistance was significantly lower in the ACEI-treated patients than in the
      controls before and after CPB (P<0.05). Renal plasma flow, measured as
      [131I]orthoiodohippuran clearance (ClH), was higher in the ACEI group than in the
      control group before CPB, as was endogenous creatinine clearance after CPB
      (P<0.05). On post-operative day 7, ClH was significantly higher in the ACEI group
      than in the control group (P<0.05). Plasma renin activity and vasopressin
      concentration increased in both groups during CPB (P<0.05). The study
      demonstrates that administration of an i.v. ACEI, enalaprilat, improves cardiac
      output during CABG surgery in patients with ischaemic heart dysfunction.
      Moreover, renal perfusion was better maintained during surgery, and this effect
      was sustained up to post-operative day 7.

PMID- 11573656
TI  - Is pulmonary resistance constant, within the range of tidal volume ventilation,
      in patients with ARDS?
AB  - When managing patients with acute respiratory distress syndrome (ARDS),
      respiratory system compliance is usually considered first and changes in
      resistance, although recognized, are neglected. Resistance can change
      considerably between minimum and maximum lung volume, but is generally assumed to
      be constant in the tidal volume range (V(T)). We measured resistance during tidal
      ventilation in 16 patients with ARDS or acute lung injury by the slice method and
      multiple linear regression analysis. Resistance was constant within V(T) in only
      six of 16 patients. In the remaining patients, resistance decreased, increased or
      showed complex changes. We conclude that resistance within V(T) varies
      considerably from patient to patient and that constant resistance within V(T) is
      not always likely.

PMID- 11573657
TI  - Gender differences in the pharmacokinetics of propofol in elderly patients during
      and after continuous infusion.
AB  - Differences in the pharmacokinetics of propofol between male and female patients
      during and after continuous infusion have not been described in detail in
      patients aged 65 yr and older. To increase our insight into the pharmacokinetics
      of propofol in this patient population and to obtain pharmacokinetic parameters
      applicable in target controlled infusion (TCI), the pharmacokinetics of propofol
      during and after continuous infusion were studied in 31 ASA class 1 and 2
      patients, aged 65-91 yr, scheduled for general surgery. Patients received
      propofol 1.5 mg kg(-1) i.v. in 1 min followed by 7 mg kg(-1) h(-1) until skin
      closure in the presence of a variable rate infusion of alfentanil during oxygen
      air ventilation. On the basis of arterial blood samples that were taken up to 24
      h post-infusion, the pharmacokinetics of propofol were evaluated in a two-stage
      manner. Multiple linear regression analysis was used to explore the effect of
      age, weight, gender and lean body mass as covariates. Gender significantly
      affected the pharmacokinetics of propofol. V3, Cl1 and Cl2 were significantly
      different between male and female patients, weight only affected Cl1. The
      pharmacokinetic parameters were: V1=4.88 litre, V2=24.50 litre, V3
      (litre)=115+147 x gender (gender: male=1, female=2), Cl1 (litre min(-1))=
      0.29+0.022 x weight+0.22 x gender, Cl2 (litre min(-1))=2.84-0.65 x gender
      (male=1, female=2), and Cl3=0.788 litre min(-1).

PMID- 11573658
TI  - Comparing the effects of stimulation and propofol infusion rate on implicit and
      explicit memory formation.
AB  - Doubt remains about the conditions under which learning persists despite
      anaesthesia. This study investigated the relative importance of dose of
      anaesthetic and stimulation for learning during propofol infusion before surgery.
      Thirty-six patients were randomly assigned to three groups. Group 1 received two
      word lists (category examples and nonsense words) during infusion of propofol to
      a target concentration of 2 microg ml(-1). Groups 2 and 3 received the word lists
      during infusion of propofol 5 microg ml(-1). Group 2 received nonsense words
      before tracheal intubation and category examples during intubation; Group 3 heard
      category examples before and nonsense words during intubation. Bispectral index
      was recorded as a measure of depth of sedation/anaesthesia. We assessed explicit
      memory on recovery using a structured interview and a recognition test. We
      assessed implicit memory using a category generation test and a preference rating
      task. To establish baseline, a control group of 12 patients completed the
      category generation test without receiving the category examples during
      anaesthesia. Overall, there was no evidence for learning during propofol
      infusion, though the category generation task showed a trend towards more
      implicit memory for words presented during intubation than during anaesthesia. We
      conclude that learning does not occur during anaesthesia without surgery.

PMID- 11573659
TI  - Absence of memory for intra-operative information during surgery with total
      intravenous anaesthesia.
AB  - While using the isolated forearm technique, we wished to determine whether
      patients who did not respond to commands during general anaesthesia with a total
      intravenous technique (propofol and alfentanil with atracurium) had any evidence
      of post-operative explicit or implicit memory. Forty women undergoing major
      gynaecological surgery were randomized, in a double-blind design, to hear two
      different tapes during surgery. Psychological tests of explicit and implicit
      memory were conducted within 2 h of surgery. There was no evidence of implicit or
      explicit memory, nor any recall, in the seven women who responded to commands
      during surgery. We conclude that during total intravenous anaesthesia with
      propofol and alfentanil, there is no evidence that learning takes place when
      anaesthesia is adequate. Furthermore, with this anaesthetic technique, it would
      seem that--provided any period of patient responsiveness is short and that
      unconsciousness is induced rapidly again--there is no evidence of implicit or
      explicit memory.

PMID- 11573660
TI  - Psychomotor recovery in very old patients after total intravenous or balanced
      anaesthesia for cataract surgery.
AB  - We compared psychomotor recovery after total intravenous anaesthesia (TIVA) with
      remifentanil/propofol and balanced anaesthesia (BAL) with
      etomidate/fentanyl/isoflurane in 40 patients, ASA I-III, aged > or =80 yr
      undergoing elective cataract surgery. Recovery times were recorded and
      psychomotor recovery was assessed according to simple reaction time, critical
      flicker fusion frequency (CFF) and short-term memory 30 min, 2 h and 1 day after
      surgery. Physical characteristics of patients in the two groups (19 in the TIVA
      group and 21 in the BAL group) were comparable. The TIVA group recovered
      significantly more quickly. Both groups showed a poorer psychomotor performance
      30 min after surgery than at baseline assessment, but simple reaction time and
      short-term memory were close to baseline values 2 h after surgery. Only
      performance in the CFF test remained below baseline at this point. No deficits in
      psychomotor performance were noted on the first day after surgery. We conclude
      that there is only a minor deficit in psychomotor function in elderly patients 2
      h after cataract surgery under general anaesthesia and that psychomotor function
      recovers completely by 24 h after surgery.

PMID- 11573661
TI  - EEG bispectral index and hypnotic component of anaesthesia induced by
      sevoflurane: comparison between children and adults.
AB  - This prospective study was designed to evaluate the correlation between the
      electroencephalographic bispectral index (BIS) and the hypnotic component of
      anaesthesia (CA) induced by sevoflurane in 27 children and 27 adult patients. BIS
      and CA were compared at loss of consciousness (LOC) and on recovery of
      consciousness (ROC). Mean (SD) BIS decreased significantly at LOC in children and
      adults from 94 (2.7) to 87.4 (4) and from 96.2 (2) to 86.7 (4.4), respectively,
      without any difference between groups. Correlation coefficients (p) between BIS
      and CA at LOC were -0.761 in children and -0.911 in adults. BIS increased
      significantly at ROC in children and adults from 74.1 (4.2) to 86.7 (2) and from
      80.2 (5) to 90.7 (3), respectively, without any difference between groups.
      Correlation coefficients between BIS and CA in ROC were -0.876 in children and 
      0.837 in adults. BIS values at ROC were not different from those at LOC in either
      group. These data demonstrate that BIS correlates with the hypnotic component of
      anaesthesia induced by sevoflurane in children as well as in adults.

PMID- 11573662
TI  - Sevoflurane EC50 and EC95 values for laryngeal mask insertion and tracheal
      intubation in children.
AB  - The laryngeal mask airway (LMA) is a simple, easy to use and safe method for
      airway control in children. Its insertion needs less anaesthetic, and
      haemodynamic responses and postoperative sequelae are less than with laryngoscopy
      and tracheal intubation. This study was designed to determine the end-tidal
      concentrations of sevoflurane where 50% (EC50) and 95% (EC95) of the attempts to
      secure the airway would be successful. We randomly assigned 40 children aged 4-12
      yr undergoing general surgery to either LMA insertion (n=20) or to laryngoscopy
      and tracheal intubation (n=20) under sevoflurane anaesthesia. The initial end
      tidal concentration of sevoflurane for each child was determined according to the
      response of the previous child in the same group. Up to three attempts to secure
      the airway with increasing sevoflurane end-tidal concentrations in 0.3% steps
      were allowed for each child. The logistic regression model was used to calculate
      the EC50 and EC95 values. Sevoflurane provided good conditions for both LMA
      insertion, and laryngoscopy and tracheal intubation without serious adverse
      effects. The EC50 and the EC95 of sevoflurane were 1.57 (SD 0.33)% and 2.22% for
      LMA insertion and 2.20 (SD 0.31)% and 2.62% for laryngoscopy and tracheal
      intubation. Thus, less sevoflurane is required for LMA insertion in children than
      for laryngoscopy and tracheal intubation.

PMID- 11573663
TI  - Effect of common airway manoeuvres on upper airway dimensions and clinical signs
      in anaesthetized, spontaneously breathing children.
AB  - Chin lift, jaw thrust and these manoeuvres combined with continuous positive
      airway pressure (CPAP) can be used to improve the patency of the upper airway
      during general anaesthesia. We used video endoscopy and measurement of stridor to
      compare the efficacy of these manoeuvres in 24 children (3-10 yr) with
      adenotonsillar hyperplasia. A bronchofibrescope was passed via the nose while the
      children were breathing spontaneously, to identify (i) the shortest transverse
      distance between the tonsils during inspiration and during expiration and (ii)
      the distance from the tip of the epiglottis to the posterior pharyngeal wall.
      Chin lift or jaw thrust lifted the epiglottis and, when combined with CPAP (10 cm
      H2O), there was a significant lateral displacement of the tonsils. Both chin lift
      plus CPAP and jaw thrust plus CPAP reduced stridor significantly compared with
      the unsupported condition. In conclusion, in spontaneously breathing children
      with large tonsils, chin lift plus CPAP is recommended, whereas jaw thrust plus
      CPAP is no better and may cause post-operative discomfort.

PMID- 11573664
TI  - Pharmacokinetics and pharmacodynamics of vecuronium in children receiving
      phenytoin or carbamazepine for chronic anticonvulsant therapy.
AB  - The pharmacokinetics and time course of action of vecuronium in normal children
      and children receiving anticonvulsant drugs for prolonged periods were
      characterized. A bolus dose of vecuronium 0.15 mg kg(-1) was administered i.v. to
      10 non-epileptic children and to 10 children on phenytoin and 10 children on
      carbamazepine, who were matched for age and weight. Plasma concentrations of
      vecuronium, 3-OH desacetylvecuronium (the primary metabolite of vecuronium) and
      alpha1-acid glycoprotein (AAG) were determined. Pharmacokinetic variables were
      derived from plasma samples collected before and after administration of
      vecuronium. Neuromuscular transmission was monitored by evoked compound
      electromyography. Recovery of the first twitch of the train-of-four (T1/T0) and
      the recovery index (RI), the time for 25-75% recovery of T1/T0, were determined.
      The elimination half-life of vecuronium was significantly reduced in both
      anticonvulsant groups compared with control [control 48.2 (SD 40.3), phenytoin
      23.5 (13.1), carbamazepine 18.4 (16.6) min, P<0.05]. Vecuronium clearance was
      increased in both anticonvulsant groups [control 9.0 (3.6), phenytoin 15.1 (8.9),
      carbamazepine 18.8 (13.1) ml kg(-1) min(-1), 0.05<P<0.1]. Children on chronic
      anticonvulsant therapy had a significantly shorter RI than control [control 21.8
      (11), phenytoin 12.5 (8.3), carbamazepine 10.6 (5.9) min, P<0.05]. Concentrations
      of vecuronium at different degrees of recovery of T1, volumes of distribution and
      AAG concentrations were not different between groups. Our data confirm
      anticonvulsant-induced resistance to vecuronium in children and support a
      pharmacokinetic component contributing to the resistance.

PMID- 11573665
TI  - Epidural analgesia and arterial reconstructive surgery to the leg: effects on
      fibrinolysis and platelet degranulation.
AB  - It has been suggested that the incidence of early graft occlusion after arterial
      reconstructive surgery to the leg may be decreased by epidural analgesia. This
      effect may be mediated by the suppression of the usual cortisol response to
      surgery, which results in increased circulating plasminogen activator inhibitor-1
      with consequent adverse effects on fibrinolysis. To investigate this and other
      potential mechanisms, 30 patients undergoing arterial reconstructive surgery to
      the leg were randomized to receive either general anaesthesia or general
      anaesthesia plus epidural analgesia. Post-operative analgesia was provided by
      morphine infusion or epidural analgesia, respectively. Blood samples were
      collected at 0, 2, 4, 6, 12 and 24 h, and 2, 3 and 5 days and analysed for
      cortisol, plasminogen activator inhibitor-1 antigen, interleukin-6 and beta
      thromboglobulin. The incidence of graft-related and systemic complications was
      recorded for 30 days. Only one patient developed early graft occlusion that
      required embolectomy and eventually amputation. There were no significant changes
      from control values in either group of patients in circulating cortisol,
      plasminogen activator inhibitor-1 and beta thrombogobulin (a marker for platelet
      degranulation). Interleukin-6 values increased significantly in both groups after
      4 h and remained elevated until day 3. There were no significant differences
      between the groups in any variable measured. We conclude that any effect of
      epidural analgesia on early graft patency is unlikely to be mediated by
      fibrinolysis or platetlet degranulation.

PMID- 11573666
TI  - Intrathecal sufentanil and morphine for post-thoracotomy pain relief.
AB  - In this double-blind randomized study we compared a group of 15 patients
      undergoing thoracotomy who received a spinal injection of sufentanil 20 microg
      combined with morphine (200 microg) after induction of general anaesthesia with a
      control group of the same size. Post-operative pain was rated on a visual
      analogue scale (VAS) and a verbal rating scale at rest and with a VAS on
      coughing. In the recovery room, patients received titrated i.v. morphine until
      the VAS score was <30, and were followed by patient-controlled analgesia (PCA)
      for 72 h. The intrathecal sufentanil and morphine group had a lower intra
      operative requirement for i.v. sufentanil and needed less i.v. morphine for
      titration in the recovery room. I.v. PCA morphine consumption and pain scores
      were lower in the active group than in the control group during the first 24 h.
      There were no differences after this time. Spirometric data (peak expiratory
      flow, forced vital capacity and forced expiratory volume in 1 s) were similar in
      the two groups. We conclude that the combination of intrathecal sufentanil and
      morphine produces analgesia of rapid onset and with a duration of 24 h.

PMID- 11573667
TI  - Spinal anaesthesia with ropivacaine 5 mg ml(-1) in glucose 10 mg ml(-1) or 50 mg
      ml(-1).
AB  - Forty patients undergoing spinal anaesthesia for a variety of surgical procedures
      were randomly allocated to receive 3 ml of ropivacaine 5 mg ml(-1) in glucose 10
      mg ml(-1) or 50 mg ml(-1). Onset of sensory block to T10 was significantly faster
      (P=0.03) with the glucose 50 mg ml(-1) solution (median 5 min, range 2-20 min)
      than with the 10 mg ml(-1) solution (median 10 min, range 2-25 min). Maximum
      extent of cephalad spread was virtually the same in both groups (10 mg ml(-1)
      median T6/7, range T3-T10; 50 mg ml(-1) median T6, range T3-T10) with similar
      times to regression beyond S2 (10 mg ml(-1) median 210 min, range 150-330 min; 50
      mg ml(-1) median 210 min, range 150-330 min). Complete motor block was produced
      in the majority of patients (10 mg ml(-1) 90%; 50 mg ml(-1) 85%) and the time to
      complete regression was the same in both groups (median 120 min, range 90-210
      min). A block adequate for the projected surgery was achieved in all patients.

PMID- 11573668
TI  - Rate of injection through whitacre needles affects distribution of spinal
      anaesthesia.
AB  - A prospective, randomized, double-blind study was performed to investigate
      whether altering the rate of injection of local anaesthetic through a Whitacre
      needle had any effect on the spinal block achieved. Twenty patients scheduled for
      elective urological surgery under spinal anaesthesia received an injection of 3
      ml of 0.5% plain bupivacaine either by hand (fast) over 10 s (18 ml min(-1)) or
      by infusion pump (slow) over 3 min (1 ml min(-1)). All patients were in the
      sitting position both during insertion of the spinal needle and for 3 min after
      the start of spinal injection, and they then changed to the supine position. The
      slow injection group achieved peak sensory block earlier, after a median interval
      of 20 (95% confidence interval 12.5-30) min vs 30 (22.5-45) min (P<0.05) for the
      fast group. The level of peak sensory block was similar: T3.5 (T2-T4.5) vs T4
      (T1.5-T6.5). The time to lowest mean arterial pressure occurred earlier in the
      slow group, at 10 (8 to 18) vs 20 (15-31) min (P<0.05). Duration of the motor
      block was shorter in the slow group: 180 (152-242) vs 270 (225-300). We conclude
      that a slow spinal injection of plain bupivacaine results in a block of more
      rapid onset and recovery.

PMID- 11573669
TI  - Comparison of relaxant effects of propofol on methacholine-induced
      bronchoconstriction in dogs with and without vagotomy.
AB  - Propofol has been suggested to have in vivo airway relaxant effects, although the
      mechanism is still unclear. In this study, we determined whether propofol could
      antagonize methacholine-induced bronchoconstriction and determined whether
      vagotomy modifies this relaxant effect. Fourteen mongrel dogs anaesthetized with
      pentobarbital and pancuronium were assigned to a control group (n=7) and a
      vagotomy group (n=7). The trachea was intubated with a special endotracheal tube
      that had a second lumen for insertion of the bronchoscope. Bronchial cross
      sectional area, which was monitored continuously through the bronchoscope, was
      measured with image analysis software. Bronchoconstriction was elicited with
      methacholine (0.5 microg kg(-1) + 5.0 microg kg(-1) min(-1)) until the end of the
      experiment. Thirty minutes after the start of methacholine infusion, propofol 0,
      0.2, 2.0 and 20 mg kg(-1) was administered. Changes in bronchial cross-sectional
      area were expressed as percentages of the basal area. Plasma concentrations of
      propofol and catecholamine were measured by high-performance liquid
      chromatography. Maximal inhibition (bronchoconstriction = 0%, baseline = 100%)
      and IC50 (concentration producing 50% inhibition of maximal effect) produced by
      propofol was obtained from each concentration-response curve using a curve
      fitting program. Methacholine decreased bronchial cross-sectional area to 49.3%
      (95% confidence interval 38.5-60.1%) and 45.3% (34.8-55.7%) of the baseline
      value. Propofol 20 mg kg(-1) significantly reversed this effect: bronchial cross
      sectional area was reduced to 77.8% (66.2-89.6%) and 75.9% (64.0-87.9) in the
      control and vagotomy groups respectively. The two groups did not differ
      significantly in the maximal inhibitory effect of propofol [control group, 61.1%
      (46.3-75.9%), vagotomy group, 64.2% (40.1-88.3%)] or pIC50 [control group 5.03
      (4.55-5.51), vagotomy group 4.86 (4.49-5.24)]. Therefore, the relaxant effects of
      propofol on methacholine-induced bronchoconstriction may not be mediated
      centrally. Propofol may relax airway smooth muscles directly or through the
      peripheral vagal pathway.

PMID- 11573670
TI  - Anaesthesia and sleep apnoea.
AB  - Sleep disordered breathing is a common problem affecting all age groups,
      particularly in association with certain other medical conditions and syndromes.
      The pathological consequences of the disorder may be severe, with significant
      implications for the perioperative management of sufferers. Research into the
      effects of surgery and anaesthesia on sleep is very much in its infancy.
      Understanding of the implications of sleep disturbance and sleep disordered
      breathing for perioperative morbidity and mortality is limited. While several
      observations have led to considerable speculation in the literature, evidence of
      a causal relationship is still largely lacking. Anaesthetists are ideally placed
      to screen large numbers of people for sleep disordered breathing, a source of
      considerable community morbidity. Recognizing the symptoms, signs and
      associations of the condition during the preoperative visit is important in
      planning management, as is recognition of the likelihood of OSA in patients who
      present difficulty with tracheal intubation or airway maintenance. Particular
      care is required in the perioperative management of patients with diagnosed or
      suspected sleep apnoea.

PMID- 11573671
TI  - Renal effects of inhaled nitric oxide in humans.
AB  - We measured renal sodium and water excretion in five healthy male volunteers who
      inhaled nitric oxide. Urine volumes, urinary sodium and creatinine, and plasma
      sodium and creatinine were measured before, during and after a 2-h period
      inhaling nitric oxide (40 vpm in air). A control experiment, excluding the nitric
      oxide, was done on a separate day. Nitric oxide increased urinary volume (mean
      increase 85%, SEM 22%) and prevented a decrease in fractional excretion of sodium
      (32% SEM 8%) seen in the control experiments, without a detectable change in
      creatinine clearance. The results suggest the inhaled nitric oxide may alter
      tubular salt and water resorbtion in humans. The mechanism for this remains
      unclear.

PMID- 11573672
TI  - Can isoflurane mimic ischaemic preconditioning in isolated rat heart?
AB  - Ischaemic preconditioning can protect the myocardium against ischaemic injury by
      opening of the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel.
      Isoflurane is also thought to open this channel. The present investigation tested
      the hypothesis that pre-ischaemic treatment with isoflurane mimics ischaemic
      preconditioning (producing chemical preconditioning) and thereby protects the
      myocardium against ischaemic injury in an isolated rat heart model. Control
      hearts underwent 30 min of global no-flow ischaemia followed by 60 min of
      reperfusion. The hearts of the preconditioning group underwent two 5 min periods
      of no-flow ischaemia interspersed with 5 min of reperfusion before the sustained
      ischaemia. In three additional groups, hearts were subjected to 15 min of 1.5
      minimal alveolar concentration (MAC) of isoflurane (ISO-1), 15 min 3 MAC (ISO-2)
      or 25 min 1.5 MAC (ISO-3) of isoflurane followed by 5 min washout before the
      global ischaemia. Left ventricular (LV) developed pressure and creatine kinase
      release were measured as variables of myocardial performance and cellular injury,
      respectively. Recovery of LV developed pressure was improved after ischaemic
      preconditioning [after 60 min reperfusion, mean 63 (SEM 6)% of baseline] compared
      with the control group [18 (4)% P<0.01] but not by isoflurane, independently of
      concentration or duration of administration [ISO-1, 17 (2)%, P=0.99 vs control;
      ISO-2, 12 (3)%, P=0.64; ISO-3, 4 (1)%, P=0.06]. Total creatine kinase release
      over 1 h of reperfusion was not significantly different between control [251 (36)
      U g(-1) dry weight] and all isoflurane groups [ISO-1, 346 (24) U g(-1), P=0.30;
      ISO-2, 313 (33) U g(-1), P=0.73; ISO-3, 407 (40) U g(-1), P=0.03]. These results
      indicate that pre-ischaemic administration of isoflurane does not cause
      anaesthetic-induced preconditioning in the isolated rat heart.

PMID- 11573673
TI  - Post-operative recovery: day surgery patients' preferences.
AB  - Due to the growing importance of quality assurance and cost containment in
      healthcare, eliciting patients' preferences for post-operative outcomes may be a
      more economical and reliable method of assessing quality. Three hundred and fifty
      five day surgery patients completed a pre-operative written questionnaire to
      identify patients' preferences for avoiding 10 particular post-operative
      symptoms: pain, nausea, vomiting, disorientation, shivering, sore throat,
      drowsiness, gagging on the tracheal tube, thirst and a normal outcome. The two
      scoring methods used to evaluate preferences were priority ranking and relative
      value scores. The effects of age, gender, previous health status, type of surgery
      and previous experience of anaesthesia on patients' preferences were also
      examined. Avoiding post-operative pain, gagging on the tracheal tube and nausea
      and vomiting are major priorities for day-case patients. Anaesthetists should
      take patients' preferences into consideration when developing guidelines and
      planning anaesthetic care.

PMID- 11573674
TI  - Attenuation of haemodynamic responses to tracheal intubation by the styletscope.
AB  - Tracheal intubation often causes a haemodynamic response probably generated by
      direct laryngoscopy. The StyletScope is a new intubation device that does not
      require direct laryngoscopy. We prospectively measured haemodynamic changes after
      tracheal intubation using the StyletScope. The increase of heart rate was less
      during tracheal intubation with the StyletScope when compared with the Macintosh
      laryngoscope.

PMID- 11573675
TI  - Unexplained acute severe methaemoglobinaemia in a young adult.
AB  - This report describes the case of an otherwise healthy young adult female, who
      presented with a 12-h history of progressive bluish discolouration of lips and
      limbs. She denied ingesting or inhaling any drug or substance. A high PaO2 in the
      presence of 'cyanosis' and 'dark blood' led to suspicion of methaemoglobinaemia.
      Co-oximetry revealed the methaemoglobin level to be 47%. A urinary screen for
      drugs of abuse was negative and blood methaemoglobin reductase activity was
      within the normal range. The aetiology was traced to dapsone detected in the
      urine by gas chromatography/mass spectrometry. The therapeutic and diagnostic
      approach in such patients is discussed.

PMID- 11573676
TI  - Total spinal anaesthesia in association with insertion of a paravertebral
      catheter.
AB  - An association between intercostal nerve block and the development of a total
      spinal is rare. Usually, subarachnoid injection is considered to have followed
      intraneural placement or inadvertent entrance into a dural cuff extending beyond
      an intervertebral foramen. We report a patient that followed injection of local
      anaesthetic into a paravertebral catheter sited at surgery in the thoracic
      paravertebral space of a patient undergoing thoracotomy. This was a life
      threatening event that occurred on two occasions before the definitive diagnosis
      was made. It is considered likely that the paravertebral catheter entered an
      intervertebral foramen and the tip perforated the dura.

PMID- 11573677
TI  - Guidelines for molecular genetic detection of susceptibility to malignant
      hyperthermia.
AB  - Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic disease
      triggered by several anaesthetic agents. The in vitro muscle contracture test
      (IVCT) is the standard test to establish an individual's risk of susceptibility
      to MH. Clinical practitioners and geneticists of the European MH Group have
      agreed on the present guidelines for the detection of MH susceptibility using
      molecular genetic techniques and/or IVCT to predict the risk of MH.

PMID- 11573678
TI  - Phaeochromocytoma diagnosed during labour.

PMID- 11573679
TI  - Phaeochromocytoma diagnosed during labour.

PMID- 11573680
TI  - Serum S100 protein as a marker of cerebral damage during cardiac surgery.

PMID- 11573681
TI  - The carina as a landmark in central venous catheter placement.

PMID- 11573682
TI  - Safe placement of central venous catheters.

PMID- 11573683
TI  - Difficult intubation in a patient with benign masseteric muscle hypertrophy.

PMID- 11573684
TI  - Internal jugular venous cannulation complicated by J-tip guide wire entrapment.

PMID- 11573685
TI  - A handmade device for difficult intubation.

PMID- 11573686
TI  - A handmade device for difficult intubation.

PMID- 11573687
TI  - For whom does the bell toll?

PMID- 11573688
TI  - Prognostic value of electrophysiologic investigations in Brugada syndrome.
AB  - INTRODUCTION: The prognostic value of electrophysiologic investigations in
      individuals with Brugada syndrome is unclear. Previous studies failed to
      determine its value because of a limited number of patients or lack of events
      during follow-up. We present data on the prognostic value of electrophysiologic
      studies in the largest cohort ever collected of patients with Brugada syndrome.
      METHODS AND RESULTS: Two hundred fifty-two individuals with an ECG diagnostic of
      Brugada syndrome were studied electrophysiologically. The diagnosis was made
      because of a classic ECG with a coved-type ST segment elevation in precordial
      leads V1 to V3. Of the 252 individuals, 116 had previously developed spontaneous
      symptoms (syncope or aborted sudden cardiac death) and 136 were asymptomatic at
      the time of diagnosis. A sustained ventricular arrhythmia was induced in 130
      patients (51%). Symptomatic patients were more frequently inducible (73%) than
      asymptomatic individuals (33%) (P = 0.0001). Fifty-two individuals (21%)
      developed an arrhythmic event during a mean follow-up of 34 +/- 40 months.
      Inducibility was a powerful predictor of arrhythmic events during follow-up both
      in symptomatic and asymptomatic individuals. Overall accuracy of programmed
      ventricular stimulation to predict outcome was 67%. Overall accuracy in
      asymptomatic individuals was 70.5%, with a 99% negative predictive value. Overall
      accuracy in symptomatic patients was 62%, with only a 4.5% false-negative rate.
      No significant differences were found in the duration of the H-V interval during
      sinus rhythm between symptomatic or asymptomatic individuals. However, the H-V
      interval was significantly longer in the asymptomatic individuals who became
      symptomatic during follow-up compared with those who did not develop symptoms (59
      +/- 8 msec vs 48 +/- 11 msec, respectively; P = 0.04). CONCLUSION: Inducibility
      of sustained ventricular arrhythmias is a good predictor of outcome in Brugada
      syndrome. In asymptomatic individuals, a prolonged H-V interval during sinus
      rhythm is associated with a higher risk of developing arrhythmic events during
      follow-up. Symptomatic patients require protective treatment even when they are
      not inducible. Asymptomatic patients can be reassured if they are noninducible.

PMID- 11573689
TI  - Foretelling the future in Brugada syndrome: do we have the crystal ball?

PMID- 11573690
TI  - Flecainide widens the excitable gap at pivot points of premature turning
      wavefronts in rabbit ventricular myocardium.
AB  - INTRODUCTION: The mechanisms by which Class IC drugs slow the rate of functional
      reentrant arrhythmias are not completely understood. We hypothesized that
      flecainide widens the excitable gap beyond the pivot point of premature turning
      wavefronts. METHODS AND RESULTS: In eight perfused subepicardial layers of rabbit
      left ventricle, a linear lesion was made by radiofrequency (RF) ablation parallel
      to the fiber orientation. One end of the RF lesion was extended by a short
      incision. Pacing next to the lesion induced a wavefront propagating with a sharp
      U-turn around the end of the lesion in either the clockwise or counterclockwise
      direction. A high-density mapping electrode (240 electrodes, 350-microm
      resolution) was used to record unipolar electrograms at the pivot point. During
      control, the shortest V1-V2 interval proximal to the pivot point was 162 +/- 12
      msec compared with 173 +/- 13 msec distal to the pivot point (difference 11 +/- 8
      msec; P < 0.01). After infusion of flecainide 2 mg/L, the shortest V1-V2 interval
      proximal and distal to the pivot point were 217 +/- 29 msec and 244 +/- 36 msec
      (difference 27 +/- 16 msec; P < 0.01). Due to the increase in V1-V2 interval at
      the pivot point, flecainide widened the temporal excitable gap in the returning
      limb of the turning wavefront from 30 +/- 11 msec to 55 +/- 22 msec (P < 0.01).
      High-density mapping at the pivot point revealed that this widening of the
      excitable gap was due to both macroscopic discontinuous conduction and functional
      conduction block at the pivot point. CONCLUSION: Flecainide widens the excitable
      gap in the returning limb of premature U-turning wavefronts by causing
      macroscopic discontinuous conduction and functional conduction block at the pivot
      point.

PMID- 11573691
TI  - Efficacy of azimilide and dofetilide in the dog right atrial enlargement model of
      atrial flutter.
AB  - INTRODUCTION: Azimilide dihydrochloride blocks both the rapid (I(Kr)) and slow
      (I(Ks)) components of the delayed rectified K+ current; dofetilide blocks only
      I(Kr). Their efficacies were assessed on atrial flutter reentrant circuits in
      dogs with surgically induced right atrial enlargement. METHODS AND RESULTS:
      Multiple biopsies of the tricuspid valve and banding of the pulmonary artery in
      male mongrel dogs made them susceptible, about 3 weeks postoperatively, to
      stimulation-induced sustained (5 min or longer) atrial flutter. Azimilide 3 mg/kg
      administered intravenously (i.v.) terminated flutter in 8 of 8 dogs, but a
      slower, nonsustained arrhythmia could be reinduced in 5. In these 5 dogs,
      azimilide 10 mg/kg terminated flutter and prevented reinduction. This dose
      increased effective refractory period significantly more in the slow conduction
      zone (25%) than in the normal zone (17%) and increased flutter cycle length
      (37%). Termination followed progressive conduction delay in the slow zone of the
      reentrant circuit. Dofetilide 1 microg/kg i.v. terminated flutter in 6 of 6 dogs,
      but the arrhythmia could be reinduced. At 3 microg/kg, flutter terminated in all
      dogs and could not be reinduced. Dofetilide also increased the effective
      refractory period significantly more in the slow zone (17%) than in the normal
      zone (12%) and increased cycle length (33%), leading to interruption of the
      arrhythmia circuit. CONCLUSION: In the canine right atrial enlargement model of
      circus movement atrial flutter, both azimilide 10 mg/kg i.v. and dofetilide 3
      microg/kg i.v. were 100% effective in terminating flutter and preventing
      reinduction. Efficacy relied on a similar mechanism of differentially prolonged
      refractoriness in the slow conduction component of the reentrant circuit where
      drug-induced termination occurred.

PMID- 11573692
TI  - Effects of azimilide, a new class III antiarrhythmic drug, on reentrant circuits
      causing ventricular tachycardia and fibrillation in a canine model of myocardial
      infarction.
AB  - INTRODUCTION: Azimilide blocks the slow (I(Ks)) and fast (I(Kr)) components of
      the delayed rectifier potassium channel. It also has blocking effects on sodium
      (I(Na)) and calcium currents (I(CaL)). Its effects on reentrant circuits in
      infarct border zones causing ventricular tachyarrhythmias are unknown. METHODS
      AND RESULTS: Activation in reentrant circuits causing sustained ventricular
      tachycardia (SVT) and the initial polymorphic tachycardia that leads to
      ventricular fibrillation (VF) was mapped in the epicardial border zone (EBZ) of 4
      day-old canine infarcts. Azimilide prolonged the effective refractory period
      (ERP) in both normal myocardium and EBZ, but reverse use-dependence in EBZ was
      prominent. Azimilide abolished SVT initiation by programmed electrical
      stimulation by prolonging the ERP at the site of stimulation either in normal or
      EBZ, preventing the occurrence of early premature impulses and the formation of
      lines of block in the EBZ necessary for formation of reentrant circuits.
      Azimilide prevented VF initiation by programmed electrical stimulation by causing
      conduction block of reentrant impulses in the EBZ during the initial beats of
      rapid polymorphic ventricular tachycardia, despite the reverse use-dependent
      effects on ERP. CONCLUSION: Azimilide has antiarrhythmic effects to prevent
      reentry causing SVT and VF in a canine infarct model.

PMID- 11573693
TI  - Preclinical evaluation of antiarrhythmic drugs: new drugs should be safe to be
      successful.

PMID- 11573694
TI  - Effects of linear, irrigated-tip radiofrequency ablation in porcine healed
      anterior infarction.
AB  - INTRODUCTION: Radiofrequency (RF) catheter ablation for ventricular tachycardia
      (VT) in healed infarction is modestly successful. More extensive, anatomically
      based procedures and irrigated RF delivery may improve outcome. However, limited
      data exist regarding the characteristics of irrigated RF lesions in infarcted
      myocardium. This study addresses this shortcoming. METHODS AND RESULTS: Linear
      lesions were created at the medial border of a healed anterior infarct in eight
      pigs using irrigated RF energy guided by sinus rhythm electroanatomic voltage
      mapping and intracardiac echocardiography (ICE). Lesion morphology and effects on
      ventricular function were assessed with ICE imaging and pathologic analysis (n =
      5). The response to programmed stimulation also was determined before and after
      linear lesions (n = 6). A mean of 9.4 +/- 1.3 RF applications created linear
      lesions 37.0 +/- 10.6 mm long, 5 to 12 mm wide, and 4 to 8 mm deep. Thrombus
      formation was not observed. Lesion delivery resulted acutely in increased local
      wall thickness at the RF site (26.9% +/- 27.5%; P < 0.0001) and transient
      systolic dysfunction in adjacent normal myocardium (fractional shortening -38% +/
      34%; P < 0.01). Uniform sustained VT (cycle length 232 +/- 41 msec) was induced
      in 4 of 6 pigs before ablation, but sustained VT could not be induced afterward.
      CONCLUSION: Irrigated RF energy produced relatively large lesions in infarcted
      myocardium without thrombus formation. Changes in tissue thickness and echo
      density observed with ICE verify irrigated RF lesion delivery. Temporary left
      ventricular dysfunction is consistently observed in the normal myocardium
      adjacent to the linear lesion.

PMID- 11573695
TI  - Irrigated radiofrequency catheter ablation.

PMID- 11573696
TI  - Calcineurin inhibition ameliorates structural, contractile, and
      electrophysiologic consequences of postinfarction remodeling.
AB  - INTRODUCTION: After myocardial infarction (MI), the heart undergoes an adaptive
      remodeling process characterized by hypertrophy of the noninfarcted myocardium.
      Calcineurin, a Ca2+-calmodulin-regulated phosphatase, has been shown to
      participate in hypertrophic signal transduction. METHODS AND RESULTS: We
      investigated the effects of calcineurin inhibition by cyclosporin A on key
      structural, contractile, and electrophysiologic alterations of post-MI
      remodeling. Male Sprague-Dawley rats were divided into four groups: (1) sham
      operated; (2) sham + cyclosporin A; (3) post-MI (left anterior descending
      coronary artery ligation); and (4) MI + cyclosporin A. Cyclosporin A (25
      mg/kg/day) was initiated 2 days before surgery and continued for 30 days.
      Hypertrophy was evaluated by echocardiography and by changes in membrane
      capacitance of isolated myocytes from noninfarcted left ventricle (LV). The
      effects of cyclosporin A on hemodynamics and cardiac dimensions were
      investigated, and changes in diastolic function were correlated with changes in
      protein phosphatase 1 activity and the basal level of phosphorylated
      phospholamban. The effects of cyclosporin A on Kv4.2/Kv4.3 genes expression and
      transient outward K+ current (I(to)) density also were evaluated. One of 12 rats
      in the post-MI group and 2 of 12 rats in the post-MI + cyclosporin A group died
      within 48 hours after MI. There were no late deaths in either MI group. There was
      no evidence of heart failure (lung congestion and/or pleural effusion) in the two
      groups 4 weeks post-MI. Calcineurin phosphatase activity increased 1.9-fold in
      post-MI remodeled LV myocardium, and cyclosporin A administration resulted in an
      86% decrease in activity. There were statistically significant decreases of LV
      end-diastolic pressure, LV end-diastolic diameter, and LV relative wall thickness
      in the post-MI + cyclosporin A group compared with the post-MI group. On the
      other hand, there was no significant difference in LV end-systolic diameter or
      peak rate of LV pressure increase between the two post-MI groups. Protein
      phosphatase 1 activity was elevated by 36% in the post-MI group compared with
      sham, and this correlated with a 79% decrease in basal level of p16
      phospholamban. In the post-MI + cyclosporin A group, the increase in protein
      phosphatase 1 activity was much less (18% vs 36%; P < 0.05), and the decrease in
      basal level of p16-phospholamban was markedly ameliorated (20% vs 79%; P < 0.01).
      The decreases in mRNA levels of Kv4.2 and Kv4.3 and I(to) density in the LV of
      the post-MI + cyclosporin A group were significantly less compared with the post
      MI group. CONCLUSION: Our results show that calcineurin inhibition by cyclosporin
      A partially ameliorated post-MI remodeled hypertrophy, diastolic dysfunction,
      decrease in basal level of phosphorylated phospholamban, down-regulation of key
      K+ genes expression, and decrease of K+ current, with no adverse effects on
      systolic function or mortality in the first 4 weeks after MI.

PMID- 11573697
TI  - Simulation of protective zones during quatrefoil reentry in cardiac tissue.
AB  - INTRODUCTION: An S3 stimulus can exert a protective effect by terminating reentry
      induced by an S2 stimulus. Our goal was to examine the mechanism by which an S3
      pulse terminates reentry and the role that virtual electrodes and break
      excitation play in this process. METHODS AND RESULTS: In our simulation, the
      bidomain model represents the electrical properties of the tissue and the Beeler
      Reuter model represents the membrane kinetics. Quatrefoil reentry is initiated by
      S1-S2 stimulation, and then a third stimulus S3 is applied at different intervals
      after S2. All stimuli are applied through the same unipolar electrode. For some
      S2-S3 intervals, the S2 and S3 wavefronts interact destructively, terminating
      reentry (protective zones). For other S2-S3 intervals, S2 and S3 wavefronts
      interact constructively, and reentry continues. Protective zones appear
      recurrently, with approximately the period of the S2 reentrant circuit. The
      protective zones are wider for anodal stimulation than for cathodal stimulation.
      CONCLUSION: Virtual electrodes, break excitation, and S2-S3 timing all play
      important roles in determining the electrical response of the tissue.

PMID- 11573698
TI  - Modulation of QT interval by cardiac sympathetic nerve sprouting and the
      mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death.
AB  - INTRODUCTION: We previously reported that there is a high incidence of sudden
      cardiac death (SCD) in dogs with myocardial infarction (MI), complete AV block
      (CAVB), and nerve growth factor (NGF) infusion to the left stellate ganglion
      (LSG). Whether or not QT interval prolongation underlines the mechanism of SCD
      was unclear. METHODS AND RESULTS: We analyzed QT intervals in three groups of
      dogs. All dogs had CAVB and MI. The LSG group (n = 9) and right stellate ganglion
      (RSG) group (n = 6) received NGF infusion via the osmotic pumps over a 5-week
      period to LSG and RSG, respectively. The control group (n = 6) received no NGF.
      The dogs either died suddenly or were sacrificed within 2 to 3 months after MI.
      Heart rhythm and QT and RR intervals were monitored using implantable
      cardioverter defibrillator ECG recordings. There was a time-dependent increase of
      QTc intervals in the LSG group and a time-dependent decrease of QTc intervals in
      the RSG group. At the end of NGF infusion, QTc intervals in the LSG group (408 +/
      41 msec) were significantly longer than those in the control (350 +/- 41 msec; P
      < 0.05) and RSG groups (294 +/- 23 msec; P < 0.01). In the LSG group, 4 of 9 dogs
      died of SCD. There was no SCD in either the RSG or control group.
      Immunocytochemical staining showed NGF infusion to LSG and RSG resulted in left
      and right ventricular sympathetic nerve sprouting and hyperinnervation,
      respectively. CONCLUSION: NGF infusion to the LSG in dogs with MI and CAVB
      resulted in increased QT interval and incidence of ventricular tachycardia,
      ventricular fibrillation, and SCD, whereas NGF infusion to the RSG shortened QT
      interval and reduced the incidence of ventricular tachycardia. These findings
      indicate that QT interval prolongation is causally related to the occurrence of
      ventricular arrhythmia in dogs with nerve sprouting, MI, and CAVB.

PMID- 11573699
TI  - QT prolongation, sudden death, and sympathetic imbalance: the pendulum swings.

PMID- 11573700
TI  - Excessive charge time delaying ventricular tachycardia therapy.
AB  - A 70-year-old man with a single-chamber implantable cardioverter defibrillator
      (ICD) placed for ventricular tachycardia presented with syncope. He was found to
      have ventricular flutter/fibrillation with capacitor charge time in excess of 1
      minute before defibrillation. The excessive charge time was secondary to ICD
      capacitor malfunction. The generator was explanted and replaced, and the patient
      recovered uneventfully.

PMID- 11573701
TI  - Accessory pathway associated with an anomalous coronary vein in a patient with
      Wolff-Parkinson-White syndrome.
AB  - We report a case of Wolff-Parkinson-White syndrome coexistent with atresia of the
      coronary sinus (CS) ostium and persistence of the left superior vena cava. The
      accessory pathway was located at the blind end of the CS, which was bumped with
      mechanical loss of preexcitation during mapping by a catheter from within the CS.
      The accessory pathway was successfully ablated with radiofrequency energy applied
      to this site from the right atrium. This unique combination of anatomically
      matched anomalies may be important in suggesting a potential embryologic link
      between the accessory pathway and the coronary vein.

PMID- 11573702
TI  - NASPE Plenary Lecture 2001. Catheter ablation: a personal perspective.
AB  - Catheter ablation for control of cardiac arrhythmias was introduced 20 years ago.
      Since then, this technique has been applied successfully to virtually all cardiac
      rhythm disturbances. In this essay, some of the newer applications of ablative
      techniques for patients with AV nodal reentrant tachycardia, atrial flutter, and
      atrial fibrillation are emphasized. "AV nodal reentrant tachycardia" may involve
      a nodofascicular tract. A new classification of atrial flutter is proposed and
      various causes of atrial fibrillation are discussed.

PMID- 11573703
TI  - Cardiac arrhythmias: from (transgenic) mice to men.
AB  - Transgenic and gene-targeted mice now are frequently used to study cardiac
      arrhythmias due to the ease with which the mouse genome can be manipulated.
      Marked electrophysiologic differences are present between the mouse and human
      heart, however, and the utility of the mouse as a model for arrhythmias and
      sudden death remains controversial. Tachyarrhythmias, bradyarrhythmias, and ECG
      in the mouse need to be interpreted with extreme care and without preconceptions
      based on our experience with humans. Despite its limitations, the mouse can
      provide a powerful tool to further our understanding of basic mechanisms that
      underlie human cardiac electrophysiology.

PMID- 11573704
TI  - Tachycardia with atrioventricular dissociation after surgery for single
      ventricle.

PMID- 11573705
TI  - Spontaneous episode of polymorphic ventricular tachycardia in a patient with
      intermittent Brugada syndrome.

PMID- 11573706
TI  - Myocardial connections between left atrial myocardium and coronary sinus
      musculature in man.
AB  - INTRODUCTION: Anatomic studies have shown that muscle morphologically identical
      to that of the atrial myocardium consistently surrounds the coronary sinus (CS).
      The CS musculature is connected to the left atrial (LA) myocardium in a variable
      fashion, with fewer connections in its distal portion. The aim of this study was
      to document the presence of connections between the LA myocardium and the CS
      musculature, using pacing maneuvers in man, and to study their potential
      association with natural atrial arrhythmia occurrence. METHODS AND RESULTS:
      Thirty patients (19 men; mean age 50.5 years) underwent electrophysiologic study,
      during which a decapolar catheter with 2-mm interelectrode spacing every 10 mm
      was inserted into the CS, with the proximal electrode pair positioned at the
      ostium. Associated atrial arrhythmias were paroxysmal atrial fibrillation in 5,
      typical atrial flutter in 13, LA flutter in 1, and other in 11. Baseline S1 and a
      single extrastimulus were delivered during distal and proximal CS pacing, while
      recordings were obtained from the four remaining bipoles. During distal CS
      pacing, double potentials with increasing interpotential interval from proximal
      to distal CS as a function of extrastimulus prematurity were detected in nine
      patients, suggesting block in a discrete local pathway distally connecting the CS
      to the LA and leading to reversion of low LA activation. Local delay in this
      pathway without complete CS-LA block resulting in LA activation fusion was
      observed in eight patients. A single nonfractionated potential at the distal CS,
      even at the shortest attainable S1-S2 coupling interval, which was interpreted as
      no block within distal CS-LA connection(s), was observed in the other 13
      patients. History of atrial fibrillation or atypical atrial flutter was found in
      8 of 9 patients with block at the distal CS-LA connection but in only 3 of 13
      patients with no CS-LA connection block (P = 0.004). CONCLUSION: The ability to
      dissociate the LA from the distal CS suggests the presence of discrete
      connections between these structures in man. This observation appears to be
      associated with the clinical occurrence of atrial arrhythmias.

PMID- 11573707
TI  - Effect of gender on atrial electrophysiologic changes induced by rapid atrial
      pacing and elevation of atrial pressure.
AB  - INTRODUCTION: The incidence of atrial fibrillation is greater in men than in
      women, but the reasons for this gender difference are unclear. The purpose of
      this study was to evaluate the effects of gender on the atrial electrophysiologic
      effects of rapid atrial pacing and an increase in atrial pressure. METHODS AND
      RESULTS: Right atrial pressure and effective refractory period (ERP) were
      measured during sinus rhythm and during atrial and simultaneous AV pacing at a
      cycle length of 300 msec in 10 premenopausal women, 11 postmenopausal women, and
      24 men. The postmenopausal women were significantly older than the premenopausal
      women (61 +/- 8 years vs 34 +/- 10 years; P < 0.01). During sinus rhythm, mean
      atrial ERP in premenopausal women was shorter (211 +/- 19 msec) than in
      postmenopausal women and age-matched men (242 +/- 18 msec and 246 +/- 34 msec,
      respectively; P < 0.05). Atrial ERPs in all patients shortened significantly
      during atrial and simultaneous AV pacing. However, the degree of shortening
      during atrial pacing (43 +/- 8 msec vs 70 +/- 20 msec and 74 +/- 21 msec; P <
      0.05) and during simultaneous AV pacing (48 +/- 16 msec vs 91 +/- 27 msec and 84
      +/- 26 msec; P < 0.05) was significantly less in premenopausal women than in
      postmenopausal women or age-matched men. CONCLUSION: The results of this study
      demonstrate a significant gender difference in atrial electrophysiologic changes
      in response to rapid atrial pacing and an increase in atrial pressure. The effect
      of menopause on the observed changes suggests that the gender differences may be
      mediated by the effects of estrogen on atrial electrophysiologic properties.

PMID- 11573708
TI  - Relationship between rehospitalization and future death in patients treated for
      potentially lethal arrhythmia.
AB  - INTRODUCTION: It is generally considered that death is the only appropriate
      endpoint to evaluate interventions for preventing death; however, this belief may
      be based on the previous use of inappropriate or inadequate surrogates for death.
      The aim of this study was to evaluate whether rehospitalization following
      implementation of an intervention is a reasonable surrogate for death. METHODS
      AND RESULTS: The time from discharge following intervention to rehospitalization
      was evaluated for 997 patients discharged after baseline hospitalization in the
      Antiarrhythmics Versus Implantable Defibrillators Trial. The relationship between
      rehospitalization for various reasons and subsequent death was compared in the
      two treatment arms to assess the adequacy of rehospitalization as a surrogate for
      death. Included were rehospitalization for: any reason, a cardiac problem, a
      noncardiac problem, new or worsened congestive heart failure (CHF), an acute
      coronary syndrome, and a cardiac procedure. For all of the reasons except cardiac
      procedure, rehospitalization was associated with a substantially increased hazard
      for subsequent death. Rehospitalization for new or worsened CHF was most closely
      (that is, temporally) related to subsequent death and was the only reason for
      rehospitalization, which fully explained the treatment effect of implantable
      cardiac defibrillators compared with antiarrhythmic drugs on death. CONCLUSION:
      Rehospitalization is a significant risk factor for subsequent death. However,
      only rehospitalization for new or worsened CHF appears to be a potential
      surrogate for death in the setting of antiarrhythmic interventions.

PMID- 11573710
TI  - Teaching residents about clinical practice guidelines using the internet.

PMID- 11573709
TI  - Follow-up of patients with unexplained syncope and inducible ventricular
      tachyarrhythmias: analysis of the AVID registry and an AVID substudy.
      Antiarrhythmics Versus Implantable Defibrillators.
AB  - INTRODUCTION: A prospective registry and substudy were conducted in the
      Antiarrhythmics Versus Implantable Defibrillators (AVID) Study to clarify the
      prognosis and recurrent event rate, risk factors, and impact of implantable
      cardioverter defibrillator (ICD) therapy in patients with unexplained syncope,
      structural heart disease, and inducible ventricular tachyarrhythmias. METHODS AND
      RESULTS: Included in the AVID registry were patients from all participating sites
      who had "out of hospital syncope with structural heart disease and EP-inducible
      VT/VF with symptoms." In addition, 13 collaborating sites provided more in-depth
      clinical and electrophysiologic data as part of a formal prospective substudy.
      Patients in the substudy were followed by local investigators for recurrent
      arrhythmic events and mortality. Registry patients were tracked for fatal
      outcomes by the National Death Index. A total of 429 patients with syncope were
      entered in the AVID registry, of whom 80 participated in the substudy. Of the
      substudy patients, 21 patients (26%) had inducible polymorphic ventricular
      tachycardia/ventricular fibrillation (VT/VF), 11 patients (14%) had sustained
      monomorphic VT <200 beats/min, and 48 patients (60%) had sustained monomorphic VT
      > or = 200 beats/min. The ICD was used as sole therapy in 75% of the syncope
      substudy patients (and with antiarrhythmic drug in an additional 9%) and in 59%
      of the syncope registry patients. Survival rates at 1 and 3 years were 93% and
      74% for the substudy patients and 90% and 74% for the registry patients,
      respectively. Survival of the syncope substudy patients (predominantly treated by
      ICD) was similar to the VT patients treated by ICD and superior to the VT
      patients treated by an antiarrhythmic drug (P = 0.05) in the randomized main
      trial. Mortality events in the substudy were marginally predicted by ejection
      fraction (P = 0.06) but not by electrophysiologic study-induced arrhythmia. The
      significant predictor of increased mortality in the registry was age (P = 0.003)
      and of reduced mortality was treatment with ICD (P = 0.006). CONCLUSION: The
      results of these analyses support the role of the ICD as primary antiarrhythmic
      therapy in patients with unexplained syncope, structural heart disease, and
      inducible VT/VF at electrophysiologic study.

PMID- 11573712
TI  - A simple five-step method for teaching clinical skills.

PMID- 11573711
TI  - A multilevel mediation approach to conflict management in a family practice
      residency program.

PMID- 11573713
TI  - Ten things I wish I had learned in residency.

PMID- 11573714
TI  - Doctor-patient relationship through the prism of Notes From the Underground by
      Dostoyevsky.

PMID- 11573715
TI  - Entry of US medical school graduates into family practice residencies: 2000-2001
      and 3-year summary.
AB  - This is the 20th report prepared by the American Academy of Family Physicians
      (AAFP) on the percentage of each US medical school's graduates entering family
      practice residency programs. Approximately 12.8% of the 15,825 graduates of US
      medical schools between July 1999 and June 2000 were first-year family practice
      residents in 2000, compared with 13.4% in 1999 and 15.4% in 1998. Medical school
      graduates from publicly funded medical schools were almost twice as likely to be
      first-year family practice residents in October 2000 than were residents from
      privately funded schools, 15.6% compared with 8.7%. The West North Central region
      reported the highest percentage of medical school graduates who were first-year
      residents in family practice programs in October 2000 at 18.2%; the Middle
      Atlantic and New England regions reported the lowest percentages at 8.3% and
      6.8%, respectively. Nearly half of the medical school graduates (47.0%) entering
      a family practice residency program as first-year residents in October 2000
      entered a program in the same state where they graduated from medical school. The
      percentages for each medical school have varied substantially from year to year
      since the AAFP began reporting this information. This article reports the average
      percentage for each medical school for the last 3 years. Also reported are the
      number and percentage of graduates from colleges of osteopathic medicine who
      entered Accreditation Council for Graduate Medical Education-accredited family
      practice residency programs, based on estimates provided by the American
      Association of Colleges of Osteopathic Medicine.

PMID- 11573716
TI  - Results of the 2001 National Resident Matching Program: family practice.
AB  - The results of the 2001 National Resident Matching Program (NRMP) reflect a
      persistent decline of student interest in family practice residency training in
      the United States. Compared with the 2000 Match, 240 fewer positions (317 fewer
      US seniors) were filled in family practice residency programs through the NRMP in
      2001, as well as 76 fewer (47 fewer US seniors) in primary care internal
      medicine, 5 fewer in pediatrics-primary care (7 fewer US seniors), and 7 fewer (1
      fewer US senior) in internal medicine-pediatric programs. In contrast, 40 more
      positions (64 more US seniors) were filled in anesthesiology and 11 more (10 more
      US seniors) in diagnostic radiology, two "marker" disciplines that have shown
      increases over the past 3 years. Ninety-one fewer positions (2 fewer US seniors)
      were also filled in categorical internal medicine, while 49 more positions (67
      more US seniors) were filled in categorical pediatrics programs, where trainees
      perceive options for either practicing as generalists or entering subspecialty
      fellowships, depending on the market. While the needs of the nation, especially
      rural and underserved populations, continue to offer a market for family
      physicians, family practice experienced a fourth year of decline though the 2001
      NRMP. Current forces, including student perspectives of specialty prestige, the
      turbulence of the health care environment, media hype, market factors, lifestyle
      choices, and student debt, all appear to be influencing many students to choose
      subspecialty rather than primary care careers.

PMID- 11573717
TI  - Teaching evidence-based medical care: description and evaluation.
AB  - BACKGROUND AND OBJECTIVES: This paper describes and evaluates several years of a
      seminar series designed to stimulate residents to seek evidence-based answers to
      their clinical questions and incorporate this evidence into practice. METHODS: At
      the first session, 86 of 89 (97%) residents completed a baseline needs assessment
      questionnaire. Post-course self-assessment questionnaires measured change from
      the first to the final seminar session in six domains of interest and skill, as
      well as residents' preferred sources of information for clinical problem solving
      up to 2 years after the course. RESULTS: Before the seminars, 48% of residents
      reported that textbooks were their most important source of information for
      solving clinical problems. A total of 58 of 75 (77%) residents completed the
      first post-course questionnaire. Residents reported significant increases in
      skill at formulating clinical questions and searching for evidence-based answers,
      appraising reviews, and deciding when and how to incorporate new findings into
      practice. Use of secondary sources of information such as "Best Evidence," moved
      up in importance from before the course to after the course. CONCLUSIONS: First
      year family practice residents who completed our seminar series have reported
      increased skill at blending consideration of a clinical problem with the use of
      secondary sources of information to access evidence to support their health care
      decisions.

PMID- 11573718
TI  - Predictors of psychosocial teaching styles in a family practice residency
      program.
AB  - BACKGROUND AND OBJECTIVES: Although physician clinical precepting has been
      extensively studied, little information exists about the teaching styles of
      behavioral science faculty. This study investigated group characteristics
      associated with two styles of teaching--authoritative and collaborative--used by
      behavioral science faculty in a family practice residency training program.
      METHODS: A 6-year retrospective study was conducted with 89 family practice
      residents and 1,228 patients. Unstructured written comments about direct
      observation of resident-patient encounters in a family practice clinic were coded
      using a combination of qualitative and quantitative approaches, then analyzed in
      relationship to variables such as gender perceived resident ability and level of
      training, ethnicity of patient, and severity of patient diagnosis. RESULTS:
      Overall, behavioral scientists used twice as many collaborative as authoritative
      teaching comments. Male behavioral scientists used more authoritative comments
      than did female behavioral scientists. First-year residents and female residents
      received more teaching generally than did their more-experienced and male
      counterparts. Perceived global performance of resident and severity of patient
      diagnosis were also related to teaching style. CONCLUSIONS: Behavioral science
      faculty should consider that group characteristics of teachers, residents, and
      patients may influence teaching style.

PMID- 11573719
TI  - Infant sleep: resident recommendations and socioeconomic status differences in
      patient practices.
AB  - BACKGROUND: Although much research has focused on parental report of infant sleep
      position since the 1992 American Academy of Pediatrics (AAP) recommendation for
      non-prone placement, few studies have examined physician recommendations
      regarding infant sleep. This study examined differences between resident
      recommendations for infant sleep position and cosleeping (bed sharing) and
      parental report of practice. We also assessed socioeconomic differences in parent
      practice, awareness, and acceptability of AAP guidelines. METHODS: We conducted a
      telephone survey of parents of 2-, 4-, 8-, and 12-month-old infants from two
      family practice centers. All 27 residents at both centers completed a paper and
      pencil survey. RESULTS: Resident recommendations and parental practices differed
      significantly for both sleep positioning and cosleeping. Parents of 165 infants
      participated, revealing that higher socioeconomic families were more aware of
      compliant with, and more accepting of AAP recommendations for supine positioning.
      CONCLUSIONS: Parents consistently report that their physician or nurse is the
      primary source of information for infant sleep. Results of this study, however,
      indicate significant differences between physician recommendation and parental
      practice and acceptability of AAP guidelines. Physicians need to continue to
      discuss this information past the newborn period.

PMID- 11573720
TI  - Disease management for diabetes among family physicians and general internists:
      opportunism or planned care?
AB  - BACKGROUND AND OBJECTIVES: Diabetes requires substantial ongoing medical
      management and use of monitoring tests. However, physicians' performance of these
      tests is often suboptimal. This study explored primary care physicians'
      management of diabetes in the context of both planned diabetes visits and acute
      visits for conditions unrelated to diabetes. METHODS: Semi-structured depth
      interviews were conducted with 12 primary care physicians in 9 family practice
      and internal medicine practices distributed throughout the state of South
      Carolina. All interviews were tape recorded and transcribed. Themes, divergences,
      and trends were identified and discussed by the investigators. RESULTS: Although
      all participants reported a preference toward planned diabetes management,
      because most patients fail to adhere to scheduled care, opportunistic disease
      management tended to be the default mode of diabetes care. Participants reported
      performing appropriate tests during scheduled visits but acknowledged that when
      confined to acute visits, diabetes care was difficult to perform. Reasons
      included time constraints and patient agenda. Participants reported that
      inadequate tracking of completion of diabetes standards of care influenced their
      adherence to guidelines. CONCLUSIONS: The current system of delivering diabetes
      care opportunistically in the context of non-diabetes acute visits may need to be
      more closely examined in an effort to improve the delivery of services.

PMID- 11573721
TI  - A program director's musings on the match and the future of family practice
      residency education.

PMID- 11573722
TI  - Learning to scramble.

PMID- 11573723
TI  - Cellular immune response in HCV infection.

PMID- 11573724
TI  - Heterogeneity found in the cagA gene of Helicobacter pylori from Japanese and non
      Japanese isolates.
AB  - We analyzed cagA genes from Helicobacter pylori strains isolated from Japanese
      and non-Japanese individuals for differences that could be associated with
      variations in virulence. The cagA genes from Japanese isolates (n = 12) and non
      Japanese American Type Culture Collection (ATCC) strains (n = 4) were sequenced
      and compared with three published sequences. Phylogenetic analysis resolved two
      distinct clusters with a genetic distance of 0.1602. Similarity plot analysis of
      the amino acid sequences identified two highly variable regions of which each was
      unique to the Japanese and non-Japanese isolates, respectively. Furthermore,
      nucleic acid sequence analysis revealed that the multiple repeated sequences
      present in cagA may have been generated by homologous recombination and/or
      misaligned replication to promote variation in the cagA gene products. Our data
      indicate that alleic variations in the H. pylori genome exist between isolates
      from Japanese and non-Japanese subjects and that distinct H. pylori populations
      may be circulating in different geographical regions. Phylogenetic analysis did
      not reveal any association of a specific CagA type with a particular disease.
      Although extensive alterations were found in the cagA gene, none of the isolates
      contained a prematurely terminated CagA protein. The cagA gene may be
      advantageous to H. pylori, possibly by aiding its escape from host immune
      recognition by antigen modulation. Thus, this ability to elude the host immune
      system may contribute to an increased risk for gastric disease.

PMID- 11573725
TI  - Virulence factors of Helicobacter pylori in Korean isolates do not influence
      proinflammatory cytokine gene expression and apoptosis in human gastric
      epithelial cells, nor do these factors influence the clinical outcome.
AB  - The cytotoxin-associated gene (cagA) and vacuolating cytotoxin (Vac) production
      have been reported to be major virulence factors of Helicobacter pylori. However,
      there have been some disputes regarding the correlation between these virulence
      factors and clinical outcomes. We evaluated whether the cagA-positive genotype
      and Vac production might be correlated with various gastroduodenal diseases in
      Korea and whether this correlation could be due to differences in proinflammatory
      cytokine gene expression and apoptosis of gastric epithelial cells in vitro. The
      presence of the cagA gene was examined by the polymerase chain reaction (PCR),
      and Vac production was detected using the bacterial culture supernatant and HeLa
      cells after H. pylori was isolated from Korean patients. Gastric epithelial cells
      were infected with cagA+Vac+, cagA+Vac-, or cagA-Vac- strains, after which
      cytokine gene expression was evaluated, using quantitative reverse transcription
      (RT)-PCR. Apoptosis and caspase-3 activation were measured in H. pylori-infected
      gastric epithelial cells. There was no significant correlation between the
      presence of these virulence factors in H. pylori isolates and peptic ulcer or
      gastric cancer. Upregulation of cytokine gene expression, including that of
      interleukin (IL)-1alpha, IL-8, granulocyte macrophage colony-stimulating factor
      (GM-CSF), and monocyte chemotactic protein (MCP)-1, as well as apoptosis and
      caspase-3 activation, were similar in infections with cagA-positive and cagA
      negative strains, but were not correlated with the production of Vac. These
      results suggest that the lack of correlation between virulence factors of
      isolated H. pylori strains and serious gastroduodenal disease entities in Korea
      may be due to the similar capacity for proinflammatory cytokine gene expression
      and apoptosis caused by infection with each of the H. pylori strains.

PMID- 11573726
TI  - Transcatheter therapy of gastric cancer metastatic to the liver: preliminary
      results.
AB  - Little is known about the effectiveness of transcatheter chemotherapy in liver
      metastases from gastric cancer. The aim of this study was to evaluate the initial
      results of hepatic artery infusion and oily chemoembolization in these liver
      secondaries. Courses of transcatheter arterial infusion with 5-fluorouracil/
      doxorubicin (12 patients) and oily chemoembolization with doxorubicin-in-iodized
      oil and gelatin sponge (12 patients) were performed in 24 patients with
      histologically proven unresectable gastric cancer liver metastases. A positive
      effect of treatment (partial response + stabilization) was seen in 92% of the
      patients after chemoinfusion and in 50% after chemoembolization. The 1- and 2
      year actuarial survival rates were 92% and 53% for infusion vs 50% and 17% for
      chemoembolization, respectively (log-rank test, P = 0.0009). For patients who had
      already died, the mean survival was 19.2 months vs 9.5 months (Student's t-test,
      P < 0.05) with median survivals of 23 months vs 8 months, respectively. The
      results with arterial infusion were very close to those reported for liver
      resection. Transcatheter therapy appears to be useful for the palliation of
      unresectable liver metastases from gastric cancer. If regional chemotherapy is
      used, arterial infusion should be the first-choice treatment, with oily
      chemoembolization being reserved for patients who do not respond to infusion.

PMID- 11573727
TI  - Hepatic stellate cells express Ca2+ pump-ATPase and Ca2+-Mg2+-ATPase in plasma
      membrane of caveolae.
AB  - Intracytoplasmic free calcium ions (Ca2+) are maintained at a very low
      concentration in mammalian tissue by the extrusion of Ca2+ across a steep
      extracellular Ca2+ gradient, mainly through the activity of plasma membrane Ca2+
      pump-ATPase. The present study aimed to identify, by electron cytochemical and
      electron immunogold methods, the ultrastructural localizations of two types of
      plasma membrane Ca2+-ATPase; Ca2+-Mg2+-ATPase and Ca2+ pump-ATPase, in hepatic
      stellate cells. Liver tissues and isolated hepatic stellate cells (HSCs) were
      studied. The ultrastructural localization of Ca2+-Mg2+-ATPase activity was
      examined by the electron cytochemical method of Ando. The localization of Ca2+
      pump-ATPase was identified by immunofluorescence. The ultrastructural
      localization of Ca2+ pump-ATPase was identified by the electron immunogold
      method. The cytochemical reaction products of Ca2+-Mg2+-ATPase activity were
      localized on the outer (cavity) side of the plasma membrane of caveolae.
      Immunofluorescence of Ca2+ pump-ATPase was seen as small dots along the cell edge
      in HSCs. Immunogold particles indicating the presence of Ca2+ pump-ATPase were
      identified on the inner (cytoplasmic) side of the plasma membrane of caveolae. We
      localized Ca2+ pump-ATPase on the inner side of the plasma membrane caveolae and
      Ca2+-Mg2+-ATPase on the outer leaflet of the caveolar plasma membrane in stellate
      cells, suggesting that Ca2+ pump-ATPase may play a key role in the Ca2+ reflux.

PMID- 11573728
TI  - Limitations of three-dimensional intraductal ultrasonography in the assessment of
      longitudinal spread of extrahepatic bile duct carcinoma.
AB  - We investigated the utility and limitations of three-dimensional intraductal
      ultrasonography (3D-IDUS), for the assessment of the extent of longitudinal
      cancer spread to the hepatic side by extrahepatic bile duct carcinoma. In eight
      patients with extrahepatic bile duct carcinoma. 3D-IDUS was used to assess
      longitudinal cancer extension to the hepatic side prior to resection. When the
      linear dimension of 3D-IDUS showed bile duct wall thickening that was connected
      to the tumor and which became thin at a point, it was determined to be the front
      formation of longitudinal cancer extension. The findings were examined in
      relation to histologic information from the resected specimen. Although 3D-IDUS
      showed front formation of wall thickening in two patients, it accurately
      reflected the histological margin of the longitudinal cancer extension in only
      one patient. In the other patient, the wall thickening was longer than the
      histological margin. When 3D-IDUS showed bile duct wall thickening without front
      formation (n = 2), the wall thickening was longer than the histological margin of
      the longitudinal cancer extension. Even when 3D-IDUS did not show wall thickening
      (n = 4), one of these patients showed cancer spread histologically. As a result,
      the accuracy in assessing longitudinal cancer extension by 3D-IDUS was only 50%.
      Even if the linear dimension of 3D-IDUS demonstrated front formation of
      thickening of the bile duct, it reflected not only cancer extension but also
      inflammatory wall thickening.

PMID- 11573729
TI  - Gastric amyloidosis with massive bleeding requiring emergency surgery.
AB  - We report a 66-year-old woman who had massive bleeding from a gastric ulcer
      complicating primary systemic amyloidosis, in whom emergency surgery proved
      lifesaving. Physical examination revealed anemia and macroglossia. Gastroscopy
      was performed, and an extensive, irregular, hemorrhagic ulcer was found in the
      gastric body. Biopsy resulted in a diagnosis of amyloidosis. On the 11th hospital
      day the patient went into shock as a result of a massive hemorrhage. Emergency
      surgery was performed, but the extent of the submucosal lesion in the stomach
      could not be identified, and total gastrectomy was unavoidable. Histological
      examination of the surgical specimen and biopsy tissue collected from other
      organs revealed amyloid deposition extending from the submucosa to the muscularis
      propria of the stomach. There was also deposition of large amounts of amyloid
      around the small blood vessels in the liver and under the mucosa of the small
      intestine. The amyloid was AA-antibody-negative and resistant to treatment with
      K2MO4, and a diagnosis of AL-type systemic amyloidosis was made. The patient's
      general condition recovered after the operation, but on the 103rd hospital day,
      she experienced sudden onset of arrhythmia and died. Patients with amyloidosis in
      whom gastrointestinal surgery is performed are rare; only 41 cases, including our
      own, have been reported in the Japanese literature since 1972.

PMID- 11573730
TI  - Strictureplasty for short duodenal stenosis in Crohn's disease.
AB  - Involvement of the gastroduodenum is extremely rare in Crohn's disease. For
      obstructing duodenal Crohn's disease, bypass procedures have traditionally been
      selected. However, more recently, strictureplasty has become an acceptable
      surgical option. We treated two Crohn's disease patients with short proximal
      duodenal stenosis, using Finney-type strictureplasty. Their postoperative courses
      were uneventful and they have remained asymptomatic during follow-up periods of
      more than 5 years, and 4 months, respectively. Owing to the good clinical results
      of our two patients, we consider strictureplasty to be indicated for short
      proximal duodenal stenosis in Crohn's disease.

PMID- 11573731
TI  - Ewing's sarcoma/peripheral primitive neuroectodermal tumor (pPNET) arising in the
      omentum as a multilocular cyst with intracystic hemorrhage.
AB  - A rare case of Ewing's sarcoma/peripheral primitive neuroectodermal tumor arising
      in the greater omentum in a 41-year-old man is reported. The patient presented
      with a hemorrhagic mesenteric cyst that was disclosed by the results of an
      abdominal echogram, a computed tomography scan, and magnetic resonance imaging. A
      laparotomy showed a multilocular cyst with intra-cystic hemorrhage.
      Histologically, the tumor wall consisted of sheets of small round cells separated
      by thick desmoplastic stroma. Rosette formations or ribbon-like cell arrangements
      were absent. Further pathological examination revealed that the membrane of the
      tumor cells was positive for MIC-2, and negative for epithelial membrane antigen,
      cytokeratin, and desmin, which are usually positive in intra-abdominal
      desmoplastic small round-cell tumors. An EWS/FLI1 fused transcript was detected
      by reverse transcription-polymerase chain reaction. These findings confirmed the
      diagnosis of Ewing's sarcoma/peripheral primitive neuroectodermal tumor. The
      patient died of tumor recurrence 4 months after his first admission. The
      autopsied tumor tissue exhibited neural differentiation in certain regions. To
      our knowledge, this is the first case to be reported of Ewing's
      sarcoma/peripheral primitive neuroectodermal tumor arising in the omentum with
      unique pathological features and the occurrence of partial neural differentiation
      during the clinical course. This case pointed out to us, as gastroenterologists,
      that only thorough examination confirms a definitive diagnosis of small round
      cell tumor of the abdomen, it also shows that Ewing's sarcoma/peripheral
      primitive neuroectodermal tumor should be included in the differential diagnosis
      of cystic lesions in the omentum.

PMID- 11573732
TI  - Idiopathic calcifying pancreatitis in a Japanese pediatric patient.
AB  - We recently experienced a rare case of chronic pancreatitis in a 13-year-old
      Japanese boy. Recently, in hereditary pancreatitis patients, some mutations have
      been identified in the trypsinogen gene. The purpose of this study was to
      investigate whether the same mutations could also be found in this patient.
      Polymerase chain reaction (PCR)-amplified products of his cationic and anionic
      trypsinogen genes were examined by direct sequence analysis. The gene analysis
      failed to show any mutation in any exons and their flanking intronic sequences of
      his trypsinogen genes. These findings indicate that the chronic calcifying
      pancreatitis in the present patient is "idiopathic", and thus a rare case of
      juvenile pancreatitis.

PMID- 11573733
TI  - Heterogeneity in the cagA gene of Helicobacter pylori and its clinical role.

PMID- 11573734
TI  - Factors to predict the outcome of Helicobacter pylori-associated gastroduodenal
      diseases.

PMID- 11573735
TI  - Transcatheter therapy for liver metastasis from gastric cancer.

PMID- 11573736
TI  - Three-dimensional intraductal ultrasonography.

PMID- 11573737
TI  - Is strictureplasty a safe and efficacious procedure for duodenal Crohn's disease?

PMID- 11573749
TI  - Seeds sown for  first farm bill of 21st century.

PMID- 11573750
TI  - Feeding normal infants: rationale for recommendations.

PMID- 11573751
TI  - Self-regulation training enhances dietary self-efficacy and dietary fiber
      consumption.
AB  - OBJECTIVE: To evaluate the effectiveness of incorporating two self-regulation
      strategies (goal setting and self-monitoring) into a nutrition education class to
      enhance dietary fiber self-efficacy and foster a positive change in dietary fiber
      consumption. DESIGN: College students in an introductory nutrition class (n =
      113) were randomly assigned to one of four treatment conditions: goal setting,
      self-monitoring, goal setting and self-monitoring, and no goal setting and no
      self-monitoring. Twenty-six college students from an introductory health class
      served as the control group. STATISTICAL ANALYSES: The main and interaction
      effects of goal setting and self-monitoring on postintervention variables were
      analyzed using analysis of covariance with baseline intake levels as the
      covariate. Analysis of variance was used to examine differences in the mean
      changes between the groups. Path analysis was conducted to analyze the causal
      linkage among the pretest and intervening variables to predict postintervention
      knowledge, self-efficacy, and fiber consumption. RESULTS: Goal setting had a
      significant main effect on dietary fiber self-efficacy and on dietary fiber
      consumption Subjects who set goals scored 15% higher on the dietary fiber self
      efficacy scale and consumed 91% more fiber than subjects who did not set goals.
      Self-monitoring had no significant main effect on either dietary fiber self
      efficacy or dietary fiber consumption. There was no significant interaction
      between goal setting and self-monitoring. Changes in dietary fiber scores
      differed between the groups. Increases in dietary fiber for the goal setting and
      self-monitoring group were significantly higher than the goal-setting, self
      monitoring, no goal setting and no self-monitoring, and control groups. In
      addition, the goal setting only group had significantly greater increases in
      fiber intake than the self-monitoring, no goal setting and no self-monitoring,
      and control groups. Changes in self-efficacy scores were significantly different
      between the groups. The goal setting and goal setting and self-monitoring groups
      had significantly higher self-efficacy scores than the control group. Path
      analysis revealed that both goal setting and self-monitoring affected dietary
      fiber consumption through knowledge and dietary fiber self-efficacy, goal setting
      had a strong direct effect on fiber consumption, and postintervention knowledge
      affected fiber consumption only through self-efficacy. APPLICATIONS/CONCLUSIONS:
      Our findings suggest that dietary change requires active self-regulation of food
      intake. Combining goal setting and self-monitoring significantly enhances dietary
      behavior change. This strategy can easily be incorporated into nutrition
      education or counseling programs to enhance dietary behavior change.

PMID- 11573752
TI  - Clinical and cost outcomes of medical nutrition therapy for hypercholesterolemia:
      a controlled trial.
AB  - OBJECTIVE: To compare the results and cost-effectiveness of a cholesterol
      lowering protocol implemented by registered dietitians with cholesterol lowering
      advice by physicians. DESIGN: Six month randomized controlled trial, cost
      effectiveness analysis. Subjects included 90 ambulatory care patients (60 men, 30
      women), age range 21 to 65 years, with hypercholesterolemia and not taking
      hypolipidemic drugs. Patients were randomly assigned to receive medical nutrition
      therapy (MNT) from dietitians using a NCEP based lowering protocol or usual care
      (UC) from physicians. Outcome measures were plasma lipid profiles, dietary
      intake, weight, activity, patient satisfaction, and costs of MNT. Changes from
      baseline for each variable of interest were compared between treatment groups
      using analysis of covariance controlling for baseline value of the variable and
      gender. RESULTS: MNT achieved a 6% decrease in total and LDL cholesterol levels
      at 3 and 6 months compared with a 1% increase and a 2% decrease in both values at
      3 and 6 months with UC (P<.001 and P<.05, respectively). Weight loss (1.9 vs 0
      kg, P<.001) and dietary intake of saturated fat (7% of energy vs 10%, P<.001)
      were better in the MNT than the UC group. The additional costs of MNT were $217
      per patient to achieve a 6% reduction in cholesterol and $98 per patient to
      sustain the reduction. The cost-effectiveness ratio for MNT was $36 per 1%
      decrease in cholesterol and LDL level. APPLICATIONS/CONCLUSIONS: MNT from
      registered dietitians is a reasonable investment of resources because it results
      in significantly better lipid, diet, activity, weight, and patient satisfaction
      outcomes than UC.

PMID- 11573753
TI  - Dietary fat reduction strategies used by a group of adults aged 50 years and
      older.
AB  - OBJECTIVE: To investigate the fat-reduction strategies used by a group of older
      adults who successfully made and maintained positive dietary changes for 5 years
      or longer. DESIGN: Participants completed 2 copies of a self-administered food
      frequency questionaire: The first copy assessed diet before they began making
      changes and the second copy assessed diet after initiation of healthful dietary
      changes. Positive food changes were identified from the food frequency
      questionnaires. During in-person interviews, participants placed food changes
      onto a time line according to the nearest estimated date of initiation of the
      change. SUBJECTS: Participants were 65 free-living older adults (aged >50 years)
      who had maintained substantial changes to decrease fat intake in their diet for
      at least 5 years. Statistical analyses performed Quantitative and qualitative
      data were used to identify the fat-reduction strategies and to confirm and
      validate the fat-reduction strategy model. Confirmatory factor analysis was
      performed to confirm the new model. The Kuder-Richardson-20 reliability
      coefficient (kr) was used to determine internal consistency of the scales
      developed for the study. RESULTS: The majority of participants decreased their
      fat intake gradually, at different time points in their lives, and over a long
      period of time (5 to 43 years). Mean percent energy intake from fat decreased
      from 44.3 +/- 5.9% before dietary improvement to 25.9 +/- 7.1% at the time of the
      study. The final model consisted of 5 fat-reduction strategies with 63 food
      changes. The strategies were: increase summer fruits (4 items; kr=0.66), increase
      vegetables and grains (14 items; kr=0.79), decrease recreational foods (14 items;
      kr=0.76), decrease cooking fat (20 items; kr=0.86), and use fat-modified foods
      (11 items; kr=0.80). APPLICATIONS/CONCLUSIONS: Dietetics professionals should
      base their advice on the dietary strategies used by consumers rather than
      hypothetical premises such as food or nutrient groupings. Nutrition education
      interventions will have better chances for success if they are based on a set of
      customized programs that guide appropriate consumer segments through a series of
      small, comfortable, and sustainable dietary changes over a prolonged period of
      time.

PMID- 11573754
TI  - Is there any research to prove that a macrobiotic diet can prevent or cure
      cancer?

PMID- 11573755
TI  - Measurement characteristics of 2 different self-monitoring tools used in a
      dietary intervention study.
AB  - OBJECTIVE: To examine the measurement characteristics of 2 self-monitoring tools,
      a food diary and fat scan, used in the dietary intervention of the Women's Health
      Trial: Feasibility in Minority Populations study. DESIGN: Comparison of fat
      intake reported on the self-monitoring tools to a criterion measure of fat
      intake, specifically the mean of a food frequency questionnaire and a 4-day food
      record. The main outcome measures were differences in fat grams and correlations
      between each of the self-monitoring tools and the criterion measure.
      SUBJECTS/SETTING: Six-month postrandomization data from 313 women aged 50 to 79
      years who participated in the intervention group of the Women's Health Trial:
      Feasibility in Minority Populations study. RESULTS: Both self-monitoring tools
      underestimated fat intake compared to the criterion measure, the food diary by 9
      g and the fat scan by 6 g. The self-monitoring instruments were better than
      chance at detecting a low-fat dietary pattern, however, and did not differ from
      each other in their ability to do so. APPLICATIONS/CONCLUSIONS: The self
      monitoring tools were modestly precise as measures of fat intake, but neither was
      sufficiently accurate to be reliable as a sole assessment of dietary adherence.
      Dietetics professionals are encouraged to assess the measurement properties of
      self-monitoring tools to use them appropriately in supporting dietary changes.

PMID- 11573756
TI  - CD-ROM nutrient analysis database assists self-monitoring behavior of active duty
      Air Force personnel receiving nutrition counseling for weight loss.
AB  - This study observed the effect of using a computerized vs manual method of self
      monitoring among Air Force personnel receiving nutrition counseling for weight
      loss. Subjects who enrolled during the first 2 weeks of the 4-week recruitment
      period completed food records for 6 weeks using a CD-ROM nutrient database
      (intervention group) whereas those who enrolled during the last 2 weeks used a
      food record booklet (comparison group). Of the 42 subjects (n = 23 intervention
      group and n = 19 comparison group), only 113 intervention and 11 comparison group
      subjects (57% of study enrollees) submitted at least 1 food record during the
      study and were included in the analysis, which included review of pre- and
      poststudy questionnaires, food records, and focus group data. There were no
      significant differences between the number of days per week documented or average
      number of items recorded daily. All 9 intervention as compared to 2 comparison
      group subjects who completed a poststudy questionnaire searched for lower-energy
      and lower-fat items and reported changing their dietary intake as a result. All
      intervention group subjects who participated in a focus group (n=6) had favorable
      comments about using the CD-ROM for monitoring and changing eating habits,
      indicating that it is a beneficial self-monitoring tool. Participants enjoyed the
      immediate dietary feedback, and computerized food records may be easier to
      interpret by nutrition counselors. A number of computerized nutrient databases
      are available to assist patients and consumers in managing nutritional concerns.

PMID- 11573757
TI  - Self-monitoring technology still requires the services of an RD.

PMID- 11573758
TI  - Program directors' opinions in regard to Didactic Program in Dietetics graduates'
      failure to secure placement in Supervised Practice Programs.
AB  - This study investigated program directors' perspectives on Didactic Program in
      Dietetics graduates' inability to secure positions in Supervised Practice
      Programs. The sample included all 229 program directors listed in the Directory
      of Dietetics Programs 1997-98. Directors contacted by electronic mail or fax
      completed a 4-part survey instrument including 3 Likert scale sections exploring
      the effects of the situation and strategies suggested to lessen them. The fourth
      part reported current practices. Response rate was 56%. Graduates' failure to
      secure Supervised Practice Program positions was found to be a significant or
      somewhat significant problem regardless of program size or affiliation.
      Strategies to increase the likelihood of Supervised Practice Program acceptance
      included work experience, application coaching, graduate coursework, and
      reapplication. We found that program directors have a high level of concern about
      their graduates' futures and are frustrated by their limited ability to improve
      the situation. Helping graduates who do not secure Supervised Practice Program
      assignments identify career options is essential.

PMID- 11573759
TI  - A longitudinal study of cognitive and affective behavior in a didactic program in
      dietetics: implications for dietetics education.

PMID- 11573760
TI  - Food safety risk identified in a population of elderly home-delivered meal
      participants.

PMID- 11573761
TI  - Aluminum, boron, calcium, copper, iron, magnesium, manganese, molybdenum,
      phosphorus, potassium, sodium, and zinc: concentrations in common western foods
      and estimated daily intakes by infants; toddlers; and male and female
      adolescents, adults, and seniors in the United States.

PMID- 11573762
TI  - Elementary students' food consumption at lunch does not meet recommended dietary
      allowance for energy, iron, and vitamin A.

PMID- 11573763
TI  - Case problem: quality of life outcomes assessment. How can you use it in medical
      nutrition therapy?

PMID- 11573764
TI  - Evidence-based practice guides vs. protocols: what's the difference?

PMID- 11573765
TI  - Use of the air displacement plethysmograph to monitor body composition: a
      beneficial tool for dietitians.

PMID- 11573766
TI  - Low-fat diets: one size may not fit all. [Interview by Jim McCaffree].

PMID- 11573767
TI  - Fruit juice consumption not related to growth among preschool-aged children
      enrolled in the WIC program.

PMID- 11573768
TI  - Prenatal WIC participation in relation to low birth weight and Medicaid infant
      costs in North Carolina--a 1997 update.

PMID- 11573769
TI  - The search is on: finding accurate molecular markers of male fertility.
AB  - Diagnosis of the fertility potential of a semen sample is essential for
      consistently high reproductive efficiency. The use of subfertile or infertile
      semen can have devastating consequences for those selling or using the semen.
      Therefore it is crucial to develop and use accurate diagnostic tests to determine
      the fertility of males and of individual semen samples. These diagnostic tests
      must be economically practical and provide consistent results. The goal of this
      review is to explore areas of fertility diagnostic research, including what we
      have termed functional and molecular tests, and consider the accuracy of each
      test. In this article, literature from several species is cited, and it is
      noteworthy that each diagnostic test may not be valuable in all species. Multiple
      functional and molecular tests will likely be needed to effectively characterize
      male fertility in each species.

PMID- 11573770
TI  - Biofilm formation and contamination of cheese by nonstarter lactic acid bacteria
      in the dairy environment.
AB  - Defects in cheese, such as undesirable flavors, gas formation, or white surface
      haze from calcium lactate crystals, can result from growth of nonstarter lactic
      acid bacteria (NSLAB). The potential for biofilm formation by NSLAB during cheese
      manufacturing, the effect of cleaning and sanitizing on the biofilm, and
      bacterial growth and formation of defects during ripening of the contaminated
      cheese were studied. Stirred-curd Cheddar cheese was made in the presence of
      stainless steel chips containing biofilms of either of two strains of
      erythromycin-resistant NSLAB (Lactobacillus curvatus strain JBL2126 or
      Lactobacillus fermentum strain AWL4001). During ripening, the cheese was assayed
      for total lactic acid bacteria, numbers of NSLAB, and percentage of lactic acid
      isomers. Biofilms of L. curvatus formed during cheese making survived the
      cleaning process and persisted in a subsequent batch of cheese. The starter
      culture also survived the cleaning process. Additionally, L. curvatus biofilms
      present in the vat dislodged, grew to high numbers, and caused a calcium lactate
      white haze defect in cheese during ripening. On the other hand, biofilms of L.
      fermentum sloughed off during cheese making but could not compete with other
      NSLAB present in cheese during ripening. Pulsed-field gel electrophoresis results
      verified the presence of the two biofilm strains during cheese making and in the
      ripening cheese. Probable contamination sites in the plant for other NSLAB
      isolated in the cheese were identified, thus supporting the hypothesis that
      resident NSLAB biofilms are a viable source of contamination in the dairy
      environment.

PMID- 11573771
TI  - Effect of heat treatments on the meltability of cheeses.
AB  - The effect of heat treatments on the meltability of cheese was investigated.
      Cheddar cheeses of different composition and low-moisture, part-skim Mozzarella
      cheese were studied at 1, 3, 6, and 12 wk of aging. Cheese samples were heated to
      60 degrees C and held for 0, 10, and 20 min before allowing the melted cheese to
      flow. Mean meltabilities, over all ages, of both Cheddar and Mozzarella cheeses
      decreased significantly as holding time increased. Meltability of young cheese
      was scarcely affected by the holding time, in sharp contrast to that of the old
      cheese where increasing the holding time greatly reduced meltability.

PMID- 11573772
TI  - Secondary structure of bovine alphaS2-casein: theoretical and experimental
      approaches.
AB  - Circular dichroism and Fourier transform infrared spectroscopy of bovine alphaS2
      casein both report a 24 to 32% content of alpha-helix. A consensus of sequence
      based predictions for alpha-helix suggests a Lys77-Gln91 helix within the
      sequence (Ser61-Arg125). This motif is repeated at (Ser143-Leu207), and this
      region contains a longer Thr145-Leu177 predicted alpha-helix. A short, seven
      member alpha-helix may also organize the N-terminal peptide that precedes the
      first phosphoserine [-Srp-]3 cluster. As was found for other caseins studied by
      these spectroscopic methods, a high degree of extended beta-sheet (approximately
      30%) and turns (25 to 30%) are predicted for alphaS2-casein.

PMID- 11573773
TI  - Nuclear magnetic resonance study of water mobility in pasta filata and non-pasta
      filata mozzarella.
AB  - Changes in molecular mobility of water in pasta filata and non-pasta filata
      Mozzarella cheeses were investigated during the first 10 d of storage using
      nuclear magnetic resonance (NMR) relaxation techniques. Water in pasta filata
      Mozzarella was classified into two fractions by spin-spin relaxation times, T21
      and T22, and corresponding proton intensities, A1 and A2, representing low and
      high molecular mobility, respectively. Increase in A1 (and decrease in A2)
      suggested that, there was a redistribution of water from more- to less-mobile
      fraction (from T22 to T21 fraction) during the first 10 d of storage. The NMR
      data did not indicate the two-state behavior of water molecules in non-pasta
      filata Mozzarella. However, the T2 values of non-pasta filata Mozzarella were
      comparable to the T21 values of pasta filata Mozzarella indicating that the
      molecular mobility of water in non-pasta filata Mozzarella is comparable to that
      of the less mobile water fraction in pasta filata Mozzarella. Generally, T2 and
      T1 values of pasta filata and non-pasta filata Mozzarella cheeses increased
      during the 10-d storage. This is believed to be due to structural changes in the
      protein matrix.

PMID- 11573774
TI  - Impact of CO2 addition to milk on selected analytical testing methods.
AB  - The addition of CO2 to raw milk and dairy products controls the growth of
      psychrotrophic bacteria at refrigeration temperatures. The objective of this
      study was to determine the effects of dissolved CO2 in milk on the performance of
      four important routine testing methods: antibiotic residue test, freezing point
      test, infrared milk component analysis, and alkaline phosphatase test. Raw or
      pasteurized whole milk was carbonated at <4 degrees C to contain approximately 0
      (control), 200, 400, 600, and 1000 ppm of CO2. The addition of CO2 to raw milk up
      to 1000 ppm had no effect on the performance of the three antibiotic (beta
      lactams) residue tests: IDEXX SNAP, Charm II Sequential Tablet, and Delvo-P
      Ampule. Milk freezing point decreased linearly with increasing concentration of
      dissolved CO2, from -0.543 degrees H (control) to -0.595 degrees H (1000 ppm).
      Carbonation to 1000 ppm decreased milk pH (measured at 38 degrees C) from 6.61
      (control) to 6.15 (1000 ppm). The effects of CO2 on milk freezing point and pH
      were reversible upon removal of dissolved CO2. Increased CO2 levels in milk
      changed the infrared absorption spectrum of milk and caused the corrected lactose
      readings to decrease and the corrected fat B readings to increase. For the
      alkaline phosphatase tests, 0 (none), 0.05, 0.1, and 0.2% raw milk were
      deliberately added to pasteurized milks of six levels of carbonation (0 to 1000
      ppm). The addition of CO2 did not influence the ability of Fluorophos, Charm
      PasLite, and Scharer Modified Rapid tests to differentiate between a pasteurized
      milk and a pasteurized milk with raw milk contamination.

PMID- 11573775
TI  - A longitudinal field trial of the effect of biotin on lameness in dairy cows.
AB  - A longitudinal prospective intervention study investigated the effect of biotin
      supplementation on the incidence (new cases per day) of visible lameness in
      milking cows and heifers on five commercial farms in Gloucestershire, United
      Kingdom. The trial lasted from June 1997 to April 1999. Each farm participated in
      the trial for 18 mo. Within each herd the cows were randomly allocated to either
      receive a supplement of 20 mg of biotin per day or not. All cows were run as one
      herd on each farm. When a lame cow was identified, the farmer called one of six
      veterinarians to examine and treat the affected animal; findings were recorded on
      a standard form. A veterinarian also carried out a bimonthly locomotion
      assessment to ensure that all lame cows were diagnosed. There were a total of 900
      cows, 1120 cow years, in the trial. The overall incidence rate of lameness (per
      100 cows per year) was 68.9, with a range of 31.6 to 111.5 per farm. The
      incidence rates of the four most frequently reported causes of lameness were sole
      ulcer, 13.8; white line separation, 12.7; digital dermatitis, 12.0; and
      interdigital necrobacillosis, 7.1 per 100 cows per year. There was a significant
      difference in the incidence rate of these four lesions between supplemented and
      unsupplemented cows on two of the five farms, with a significant decrease in
      lameness in the cows supplemented with biotin. When all the farms were pooled,
      the risk of lameness caused by white line separation in cattle supplemented with
      biotin was approximately halved (Cox proportional hazard survival analysis hazard
      ratio = 0.57).

PMID- 11573776
TI  - Technical note: Therapeutic cessation of lactation of Staphylococcus aureus
      infected mammary quarters.
AB  - The objective of the present study was to compare the ability of chlorhexidine
      and povidone-iodine to cause cessation of lactation in Staphylococcus aureus
      infected mammary quarters, assess milk production in the treated quarter in the
      subsequent lactation, and evaluate whether microbiological cure was obtained.
      Fourteen mid- to late-lactation Holstein-Friesian dairy cattle from the
      Washington State University dairy herd with single mammary quarter S. aureus
      intramammary infections were studied. Cows were randomly assigned to one of two
      treatment groups, povidone-iodine or chlorhexidine. Cows in the povidone-iodine
      group were infused with 120 ml of 5% povidone-iodine solution (0.5% iodine) after
      complete milk-out. Chlorhexidine-treated cows were infused with a proprietary
      chlorhexidine suspension after two milkings 24 h apart. Treated mammary quarters
      were not milked for the rest of the lactation. Milk production from each mammary
      quarter (kg of milk/quarter) was measured using in-line volume flow meters for 5
      consecutive days before treatment and again at the start of the subsequent
      lactation. Povidoneiodine caused permanent cessation of lactation in the treated
      quarter, whereas 71% of the chlorhexidine-treated mammary quarters returned to
      function in the subsequent lactation. Hence, if the primary objective is to
      eliminate the mammary quarter from lactation, and thereby presumably lower the
      risk of herdmates acquiring new S. aureus intramammary infection, then povidone
      iodine appears to be the best of the two methods. No difference in total milk
      production between lactation one and two in either group was found, suggesting
      that permanent loss of a quarter was not detrimental to overall milk production.

PMID- 11573777
TI  - The effects of frequency of feeding a total mixed ration on the production and
      behavior of dairy cows.
AB  - Two experiments were conducted to examine the response of Friesian dairy cows to
      different frequencies of feeding a total mixed ration. The first compared
      alternate day with daily feeding. Cows fed on alternate days spent longer
      feeding, had increased dry matter intakes, and produced more milk, but with
      reduced protein content, compared with cows fed daily. Those fed daily increased
      feeding greatly after the food was offered to them. Those fed on alternate days
      had a smaller increase in feeding when food was offered, and their feeding
      pattern was similar on feeding and nonfeeding days, suggesting that they could
      not anticipate the time that food would be offered. However, on days when no food
      was provided they were less aggressive than cows fed daily. Cows fed daily spent
      less time grooming themselves and more time standing, suggesting that the extra
      feeding caused disturbance. A second experiment compared frequent feeding (four
      times per day) with infrequent feeding (once daily), with the cows fed
      infrequently being either housed with or apart from the cows fed frequently, to
      determine whether the disturbance of feeding other cows would affect cows housed
      in the same building but not fed frequently. Both groups of frequently fed cows
      spent less time feeding in the morning and more in the evening and had less
      circadian variation in sleeping and lying ruminating, compared with both groups
      of cows fed infrequently. Cows fed infrequently and housed by themselves produced
      more milk but with reduced milk protein concentration, compared with the
      infrequently and frequently fed cows that were housed together. They also spent
      more time standing in the feeding passage, not ruminating, and more time grooming
      themselves, indicating less disturbance. Thus cows fed infrequently had reduced
      milk yield if they were housed with frequently fed cows, and it is concluded that
      in both experiments frequent feeding disturbed the cows and reduced milk
      production.

PMID- 11573778
TI  - The effect of lameness on milk production in dairy cows.
AB  - Data were collected prospectively for 1.5 yr on two New York dairy farms to
      investigate the effect of lameness on milk production. The numbers of study cows
      (percentages treated at least once for lameness) in each herd were 1796 (52%) and
      724 (40%), respectively. Lame cows were identified and treated by farm employees
      or a professional hoof trimmer. Weekly averages of total milk production per day
      were recorded based on automated milk weight measurements at each milking. The
      effect of lameness on milk production was analyzed separately for each herd using
      repeated measures ANOVA. In both herds, milk production decreased significantly
      for cows diagnosed lame. Milk production was 1.5 kg/d lower > or = 2 wk after
      lameness compared with cows that had not yet been diagnosed lame in the current
      lactation in the larger herd. In the second herd, milk production of lame cows
      was 0.8 kg/d lower in the first and second wk after lameness and 0.5 kg/d lower >
      or = 3 wk after diagnosis. The decrease in milk production associated with
      lameness was larger for cows in second or greater lactation and for more severe
      cases. In one herd, the decrease in milk production was greater for cows with
      sole ulcers or foot abscesses than for foot rot or foot warts. Cows with
      abscesses or foot rot tended to have larger decreases in milk production in the
      other herd. The inconsistent results between farms may have resulted from
      differences in the relative frequencies of specific causes of lameness in the two
      herds and in the way lame cows were identified and defined for the study.

PMID- 11573779
TI  - Dexamethasone influences endocrine and ovarian function in dairy cattle.
AB  - Multiparous nonlactating Holstein cows were used to determine the effect of
      dexamethasone on ovarian follicular development and plasma hormone
      concentrations. Animals were randomly divided into two groups, control (C; n = 5)
      and treatment (T; n = 6), but managed as one group. Both groups were synchronized
      with two injections of PGF2alpha (25 mg i.m.) 11 d apart. One day after ovulation
      (d 0) the T group received a daily injection of dexamethasone (44 microg/kg of
      body weight; i.m.) until the first dominant follicle stopped growing or up to d
      12 postovulation. The C group received vehicle injections. Blood samples were
      collected daily from all cows. Concentrations of LH and FSH did not differ
      between the C and T cows, whereas progesterone concentrations were lower in T
      than in C cows from d 4 onward. Treatment x day interaction influenced plasma
      insulin concentrations such that T cows had insulin concentrations 2.9- to 6.0
      fold those of C cows between d 2 and 9. Dexamethasone decreased IGF-I and -II
      concentrations from d 5 onward. Concentrations of plasma leptin and the various
      IGF binding proteins were not affected by dexamethasone. Total number of
      follicles (> or = 5 mm) and plasma estradiol concentrations were less in T than
      in C cows on d 0, 1, and 4. The growth rate of the dominant follicles and maximum
      diameter of the dominant and subordinate follicles were not affected by
      dexamethasone. The diameter of the CL was 21 to 39% larger in T than in C cows
      between d 6 and 10. Treatment x day interaction influenced plasma cholesterol
      concentrations such that cholesterol levels decreased 46.8% in T cows and 19.5%
      in C cows between d 0 and 10. Plasma glucose concentrations were greater in T
      than in C cows between d 1 and 10. In summary, dexamethasone had significant
      effects on metabolism without a major impact on growth of the first-wave dominant
      follicle. Dexamethasone-induced suppression of luteal function was associated
      with decreased plasma IGF-I and -II concentrations.

PMID- 11573780
TI  - Evaluation of a systemic antibiotic treatment of toxic puerperal metritis in
      dairy cows.
AB  - The objective of this study was to evaluate the efficacy and economic efficiency
      of a systemic treatment of toxic puerperal metritis in dairy cows with ceftiofur.
      Cows with abnormal vaginal discharge at a postpartum examination (d 4 to 6 after
      calving) and a rectal temperature > or = 39.5 degrees C were assigned to three
      treatment groups. Cows in group 1 (n = 70) received 600 mg of ceftiofur
      intramuscularly (i.m.) on 3 consecutive days. Cows in group 2 (n = 79) received
      an intrauterine treatment with antibiotic pills consisting of 2500 mg of
      ampicillin and 2500 mg of cloxacillin and an additional 6000 mg (i.m.) of
      ampicillin. This treatment was performed on 3 consecutive days. Cows in group 3
      (n = 78) received the same intrauterine treatment as in group 2. In addition, 600
      mg of ceftiofur was administered i.m. on 3 consecutive days. Body temperature was
      recorded daily for 6 d after first treatment. There were no significant
      differences among the groups regarding clinical efficacy at d 6 after first
      treatment. The cure rates based on rectal temperatures declining to below 39.5
      degrees C on d 6 after treatment were 82.9, 84.8, and 84.6% for groups 1, 2, and
      3, respectively. Reproductive performance did not differ significantly between
      group 1 and groups 2 and 3 for any of the measures tested. A financial analysis
      with 87 different cost scenarios demonstrated that a systemic treatment of toxic
      puerperal metritis in cattle with ceftiofur is an effective alternative to the
      combination of local and systemic treatments.

PMID- 11573781
TI  - Sensitivity and specificity of somatic cell count and California Mastitis Test
      for identifying intramammary infection in early lactation.
AB  - Associations between values for the somatic cell count (SCC) or the California
      Mastitis Test (CMT) and intramammary infection (IMI) were studied in 131 dairy
      cows from three herds during the first 10 d post-calving. Intramammary infection
      was defined as the presence of one or two bacterial species in one or both
      quarter milk samples taken within 12 h of calving and at d 3 postcalving. Quarter
      milk samples identified IMI in 36% of glands. Values for SCC declined at a
      significantly faster rate over the first 10 d postcalving in non-infected
      quarters than in infected quarters. The usefulness of quarter milk SCC and CMT
      for screening was evaluated by calculating the sensitivity and specificity for
      various threshold values and days postcalving. A SCC threshold of 100,000
      cells/ml for quarter samples evaluated on d 5 postcalving had the maximal
      sensitivity and specificity for detecting IMI. Evaluation of the CMT samples
      taken on d 3 postcalving using a threshold reaction of greater than zero had the
      highest sensitivity and specificity for detecting IMI. With this CMT sampling
      scheme, the sensitivities for detecting IMI with any pathogen, IMI with a major
      pathogen, and IMI with a minor pathogen were 56.7, 66.7, and 49.5, respectively.
      The CMT could have a useful role in dairy herd monitoring programs as a screening
      test to detect fresh cows with IMI caused by major pathogens.

PMID- 11573782
TI  - The relationship between milk yield and the incidence of some diseases in dairy
      cows.
AB  - Logistic regression models were used to examine the relationship between milk
      yield and incidence of certain disorders. Lactations (n = 2197) of 1074 Holstein
      Friesian cows from 10 dairies (25 to 146 cows per dairy) in Lower Saxony were
      studied. The 305-d yield from the previous and current lactations served as the
      standards for milk yield. Eight disorder complexes were considered: retained
      placenta, metritis, ovarian cysts, mastitis, claw diseases, milk fever, ketosis,
      and displaced abomasum. Each disorder complex was modeled separately. In addition
      to milk yield, the influences of the lactation number, the calving season and the
      other disorder complexes were examined with the "herd" factor taken into account.
      A correlation between retained placenta, mastitis, and milk fever to milk yield
      during the previous lactation was found to be probable and for ketosis and
      displaced abomasum such a correlation was found to be possible. A connection to
      the yield in the current lactation was shown for ovarian cysts, claw diseases,
      and milk fever. No relationship to milk yield existed for metritis. An influence
      of the lactation number was also demonstrated in various models. Single models
      allowed a demonstration of the influences of both milk yield and lactation
      number. Limitations of the model types are discussed.

PMID- 11573783
TI  - Environmental gram-positive mastitis treatment: in vitro sensitivity and
      bacteriologic cure.
AB  - A clinical trial was conducted in a large dairy herd to determine the efficacy of
      intramammary pirlimycin hydrochloride administration during lactation for
      bacteriologic clearance of gram-positive environmental clinical and subclinical
      mastitis infections. Quarters infected with environmental streptococci that
      received pirlimycin therapy (13/28) were 1.8 times more likely to resolve
      infection than untreated quarters (5/14). The small numbers of quarters infected
      with coagulase-negative staphylococci resulted in inadequate power to assess
      treatment differences in cure rate. Although the association was not
      statistically significant, quarters from cows with sensitive environmental
      streptococci isolates from composite samples (8/13) resolved infection with
      treatment at approximately twice the rate of treated quarters with resistant
      isolates (3/10).

PMID- 11573784
TI  - Bovine mammary immune response to an experimental intramammary infection with a
      Staphylococcus aureus strain containing a gene for staphylococcal enterotoxin C1.
AB  - Staphylococcal enterotoxin C (SEC), a superantigen, is the most frequently
      expressed enterotoxin by bovine strains of Staphylococcus aureus causing
      mastitis. To examine the possible impact of SEC on the immune response of the
      bovine mammary gland, we monitored changes in lymphocyte subpopulations in
      mammary glands of four lactating cows after intramammary instillation of S.
      aureus strain Rn4220 transformed with a plasmid containing a gene coding for
      SEC1. Four other lactating cows received the same strain transformed with the
      plasmid without the SEC1 gene (positive control), and four cows were untreated
      (negative control). Mammary quarter milk samples for somatic cell count (SCC)
      analysis and determination of N-acetyl-beta-D-glucosimindase (NAGase) activity
      levels were collected daily for 21 d postinstillation. Flow cytometry utilizing
      three-color analysis was used to phenotype lymphocyte subpopulations isolated
      from milk samples collected on d 0, 4, 7, 11, 14, 18, and 21 postinstillation
      from all the cows. Milk from mammary gland halves (positive control and
      experimental) or all mammary quarters (negative control) was collected for flow
      cytometric analysis. Increased NAGase activity, SCC, and isolated S. aureus
      demonstrated that infection was established in mammary quarters intrammarily
      instilled with bacteria. There were no significant differences (P > 0.05) in the
      proportions of BoCD4 helper T lymphocytes or BoCD8 cytotoxic T lymphocytes
      between the two infected treatment groups. There was a significant day x
      treatment difference of the proportion of a gammadelta T cell subpopulation that
      did not express BoCD2, but did express the ACT2 activation molecule and a
      significant treatment difference of a gammadelta T cell subpopulation that
      expressed BoCD2, but not the ACT2 activation molecule (P < 0.05). Results do not
      support the hypothesis that the presence of the gene for SEC1 alters the mammary
      BoCD4 or BoCD8 T lymphocyte response to infection.

PMID- 11573785
TI  - Effects of prepartum dry matter intake and forage percentage on postpartum
      performance of lactating dairy cows.
AB  - The objective of this research was to determine whether different dry matter
      intakes (DMI) or forage percentages prepartum would have an impact on postpartum
      performance. Multiparous Holstein cows (n = 41) received either high (H) or low
      (L) forage rations that were fed free choice (F) or restricted (R), i.e., HF, HR,
      LF, and LR. The L rations were higher in net energy of lactation and lower in
      neutral detergent fiber concentrations. After calving, all cows were fed the same
      ration ad libitum. Prepartum DMI were 8.0 for R versus 12.4 kg/d for F with LF
      greater than HF (14.1 vs. 10.7 kg/d). Prepartum treatments did not affect
      postpartum means for DMI, milk yield, milk protein percentage, body weight, body
      condition score, or plasma glucose concentrations (overall means 1 to 40 DIM
      were, respectively, 21.1 kg/d, 34.0 kg/d, 3.03%, 624 kg, 3.2, and 66 mg/dl).
      However, curves from 1 to 40 DIM showed that DMI and milk yield were slightly
      higher in early lactation in cows whose DMI had been restricted prepartum but
      mean milk fat percentage was lower (3.10 vs. 3.42%). Plasma NEFA were higher and
      insulin lower in H versus L before and after calving. High DMI prepartum, at
      best, showed no advantage over restricted feeding.

PMID- 11573786
TI  - Formulation of colostrum supplements, colostrum replacers and acquisition of
      passive immunity in neonatal calves.
AB  - Provision of an adequate mass of IgG from maternal colostrum is essential to
      health and survival of neonatal calves. Colostrum supplements (CS) have been
      developed to provide supplemental immunoglobulin when maternal colostrum is of
      poor quality. However, colostrum replacers (CR) that provide > or = 100 g of IgG
      have not been formulated. Our objective was to determine the absorption of IgG in
      newborn calves fed CS derived from bovine serum or CR derived from bovine
      immunoglobulin concentrate. The CS were prepared by collecting, processing, and
      spray drying bovine serum and blending with other ingredients to provide 45 to 50
      g of IgG per dose. The CR were prepared by further processing bovine serum to
      increase IgG concentration to > 50% IgG and blending with other ingredients to
      provide 100 to 122 g of IgG per dose. Holstein calves (n = 160) were fed 90 to
      244 g of IgG from CS or CR in 1 or 2 feedings in two experiments. Blood was
      collected from each calf by jugular venipuncture at 0 and 24 h of age and plasma
      IgG was determined by turbidimetric immunoassay. Apparent efficiency of IgG
      absorption was calculated. Plasma IgG concentrations at 24 h of age were
      indicative of IgG intake and averaged 5.5 to 14.1 g/L in calves fed CS and CR.
      Mean apparent efficiency of IgG absorption in calves fed CS was 25 and 28% in
      experiments 1 and 2, respectively. Mean apparent efficiency of IgG absorption in
      calves fed CR ranged from 19 to 32% and were affected by method of processing and
      number of times fed. Treatment of plasma with polyethylene glycol reduced the
      efficiency of IgG absorption in experiment 1. The addition of animal fat to CR
      had no effect on IgG absorption. A second feeding of CR increased plasma IgG, but
      efficiency of absorption was reduced. Mean body weights at 60 d of age were not
      affected by treatment and ranged from 64.3 to 78.2 kg. Plasma IgG concentration
      in calves fed > or = 122 g of IgG from Ig concentrate approached (9.9 g/L) or
      exceeded 10 g/L, indicating successful transfer of passive immunity. Provision of
      IgG to prevent failure of passive transfer is possible with CR containing >20%
      IgG when fed at 454 g per dose.

PMID- 11573787
TI  - Diurnal variation in pH reduces digestion and synthesis of microbial protein when
      pasture is fermented in continuous culture.
AB  - Many models of digestion assume steady-state conditions and do not account for
      diurnal variation in the rumen environment. This experiment examined the
      relationships between diurnal pH, pasture digestion, and microbial protein
      synthesis. Four dual-flow continuous culture fermenters were used to test the
      effect of increasing time at suboptimal pH on parameters of digestion.
      Fermentation of high quality pasture was controlled at pH 5.4 (suboptimal) for
      four intervals during each 24-h period (0, 4, 8, and 12 h) according to a 4 x 4
      Latin square design. During the remainder of each day, pH was controlled at 6.3
      (optimal). Samples were collected during the last 3 d of each of the four 9-d
      experimental periods. A negative quadratic relationship was observed between time
      at suboptimal pH and apparent digestibility of organic matter and dry matter. The
      largest reduction in digestibility of organic matter, dry matter, and neutral
      detergent fiber was exhibited after 4 h at suboptimal pH. A negative linear
      relationship was found between time at suboptimal pH and microbial N flow, with
      the greatest decline in microbial N flow occurring at 12 h at suboptimal pH.
      These results suggest that the period of time that pH is below optimal may be
      more critical for digestion than the relationship between mean daily pH and
      optimal pH. Modeling non-steady-state ruminal conditions to account for diurnal
      variation in the ruminal environment may improve the prediction of digestion,
      especially fiber.

PMID- 11573788
TI  - Implementation of a routine genetic evaluation for longevity based on survival
      analysis techniques in dairy cattle populations in Switzerland.
AB  - Genetic evaluation of sires for functional longevity of their daughters based on
      survival analysis has been implemented in the populations of Braunvieh,
      Simmental, and Holstein cattle in Switzerland. A Weibull mixed sire-maternal
      grandsire survival model was used to estimate breeding values of sires with data
      on cows that calved since April 1, 1980. Data on Braunvieh and Simmental cows
      included about 1.1 million records, data on Holstein cows comprised about 220,000
      records. Data contained approximately 20 to 24% right-censored records and 6 to
      9% left-truncated records. Besides the random sire and maternal grandsire
      effects, the model included effects of herd-year-season, age at first calving,
      parity, stage of lactation, alpine pasturing (Braunvieh and Simmental), and
      relative milk yield and relative fat and protein percentage within herd to
      account for culling for production. Heritability of functional longevity,
      estimated on a subset of data including approximately 150,000 animals, were
      0.181, 0.198, and 0.184 for Braunvieh, Simmental, and Holstein, respectively.
      Breeding values were estimated for all sires with at least six daughters or three
      granddaughters in the data. Breeding values of sires are expressed in months of
      functional productive life and published in sire catalogs along with breeding
      values for production traits.

PMID- 11573789
TI  - Twinning rates for North American Holstein sires.
AB  - Calving data of North American Holsteins were analyzed using a linear sire model
      and a threshold sire model to estimate fixed effects and sire predicted
      transmitting abilities (PTA) for twinning rate. The data were 1,324,678 births of
      37,174 sires of cows from the National Association of Animal Breeders (NAAB)
      calving ease database. All twins were assumed to be dizygotic. Triplets were not
      included in the analysis. The twinning rate was 5.02%. The sire model included
      relationships among sires and fixed effects of herd-years, season, parity, and
      sire groups. Different estimates of heritability due to models and restrictions
      on data have been demonstrated. Heritability estimates for the sire of the cow
      effect were 2.10% by the linear model analysis and 8.71% by the threshold model
      analysis. Sire PTA for twinning rate ranged from 1.6 to 8.0%. Mean incidence of
      twins increased from first to fifth and later parities: 1.63, 5.22, 6.66, 7.19,
      and 7.19%, respectively. Some changes with season were also evident. The
      incidence of twins was highest in April to June, at 5.88%, and lowest in October
      to December, at 4.23%. Sire group effects showed that sires born after 1990 had a
      higher incidence of twins than sires born before 1990. The mean twinning rate for
      sires born before 1980 was 4.55% compared with a mean of 5.58% for sires born
      after 1991. Characteristics of individual sire evaluations are discussed. Ample
      opportunity exists to change the incidence of twins in the Holstein population.
      Sire selection can be used to reduce the incidence of twins and also the
      increased cost of production associated with twins. From a national perspective,
      a reduction in the incidence of twin births can result in a saving of as much as
      $55 million per year.

PMID- 11573790
TI  - Accuracy of recorded birth and calving dates of dairy cattle in the United
      States.
AB  - Frequencies of births that were reported for specific days of the month were
      documented for US dairy cattle born since 1987 by birth year, herd size, and
      registry status and compared with calving frequencies for those dates. Because
      birth dates are expected to be random and uniformly distributed throughout each
      month, percentages of births on individual dates were expected to be equal (3.3%
      for d 1 to d 28, 3.2% for d 29, 3.0% for d 30, and 1.9% for d 31). However,
      percentages of reported birth dates for d 1, 2, 10, 15, and 20 were higher than
      expected. The percentage of reported births for d 1 was highest (5.3%) of all
      days of the month regardless of herd size or registry status. The nonuniform
      distribution of birth dates within month indicated that a substantial number of
      birth dates were unknown and that estimated birth dates had been reported. About
      one-third of the birth dates recorded on d 1 appeared to have been estimated, or
      altered to gain an advantage in cattle shows. The highest frequencies for birth
      dates on d 1 (5.9 to 7.4%) were found for registered cows during months that
      initiated age groupings for dairy shows (March, June, September, and December).
      Birth dates for some registered cows were intentionally misreported as confirmed
      by comparison of birth dates of individual cows with calving dates of their dams.
      Reported calving dates appeared to be more accurate than reported births; the
      inflated frequency of recorded calvings on d 1 was only about 30% as large as the
      inflated frequency of recorded births. Because cow age is determined by birth
      date, proper reporting of birth dates is important to ensure the accuracy of
      standardized yield and fitness records and the genetic evaluations that are based
      on those records. When animals' recorded birth dates and their dams' calving
      dates differ, more credence should be given to the latter to improve accuracy.

PMID- 11573791
TI  - Past, present, and future perspectives of small ruminant dairy research.
AB  - The objectives of this paper are to review small ruminant dairy research in
      relation to the dimensions of the dairy goat and dairy sheep industries in the
      United States and the world. At least 10 countries depend on goats and sheep for
      between 30 to 76% of total milk supply. Leading among developed countries is
      Greece producing 178 kg milk per person per year with 61% from sheep and goats.
      Most developing countries need research, extension service, and public support to
      improve apparent productivity of goats and sheep. Domestic supply from all milk
      sources is <100 kg/person per year, and annual apparent yields average <100 kg of
      milk/goat, <50 kg of milk/sheep, which makes supplies of animal protein and
      calcium from domestic sources very low. Statistical data on goat and sheep
      production for United States are not available. The small population of DHIA
      tested US dairy goats averaged in recent years >700 kg of milk/goat per year, and
      some dairy sheep breeds may produce as much as 650 kg/yr. The need for more milk
      availability appears to be reflected in the dramatic increases of dairy goat
      populations during the last 20 yr: 52% for the world, 56% for developing, 17% for
      developed countries, while sheep populations decreased by 3% for the world, by 6%
      in developed, but increased 14% in developing countries. Research has been sparse
      on the unique qualities of goat and sheep milk compared with cow milk. Much
      development work by various agencies has been devoted to reducing mortality and
      improving feed supplies in harmony with the environment; this work is mostly
      published in proceedings of scientific meetings, often not in English. Results
      have shown in many cases that dairy goats and dairy sheep can be very profitable,
      even in developing countries with difficult climate and topographical conditions.

PMID- 11573793
TI  - The solvent extraction of radium using sym-Di[4(5)-tert-butylbenzo]-16-crown-5
      oxyacetic acid.
AB  - The extraction of radium using sym-Di[4(5)-tert-butylbenzo]-16-crown-5-oxyacetic
      acid (DTBDB16C5-OAcH) in toluene is excellent. The reaction is reversible without
      counterions at pH higher than 9. The distribution ratio decreases as the
      dissolved concentration of alkaline earth ions increases. Probed factors involved
      in this solvent extraction system include pH values, solvents, metal ions, and
      the concentration of DTBDB16C5-OAcH. Liquid scintillation cocktails including
      Ultima Gold and Hionic Fluor were also evaluated in liquid scintillation
      counting.

PMID- 11573792
TI  - A new method for separation of 131I, produced by irradiation of natural uranium.
AB  - Separation of 131I from natural uranium fission product mixtures has been
      accomplished by sorbing the 131I on special platinum-charcoal sorbent and
      desorbing by buffer solution (NaHCO3+Na2S2O3). High radiochemical and chemical
      purity is obtained by this method. Important parameters such as temperature,
      distillation rate, sorbing and desorbing rates and 131I separation yields have
      been investigated.

PMID- 11573794
TI  - Thermal neutron reflection method for measurement of total hydrogen contents in
      Ghanaian petroleum products.
AB  - A fast and non-destructive technique based on thermal neutron reflection was used
      to determine total hydrogen contents in petroleum products available in Ghana. A
      source holder consisting of an 241Am-Be neutron source and 3He neutron probe
      designed for detection of liquid levels was used to measure reflection parameter
      as a function of hydrogen contents in liquid hydrocarbons which served as
      standards. The measured data were fitted to two linear equations for two
      different geometrical arrangements. The trend of data was found to be consistent
      with theoretical analysis based on neutron moderation. The calibration lines were
      used to determine hydrogen contents in 10 petroleum products. The results agree
      favourably with those obtained using different experimental set-ups with other
      neutron sources and probes. The technique was also used to determine the quality
      of diluted petrol with aviation fuel.

PMID- 11573795
TI  - Dose compensation of the total body irradiation therapy.
AB  - The aim of the study is to improve dose uniformity in the body by the compensator
      rice and to decrease the dose to the lung by the partial lung block. Rando
      phantom supine was set up to treat bilateral fields with a 15 MV linear
      accelerator at 415cm treatment distance. The experimental procedure included
      three parts. The first part was the bilateral irradiation without rice
      compensator, and the second part was with rice compensator. In the third part,
      rice compensator and partial lung block were both used. The results of
      thermoluminescent dosimeters measurements indicated that without rice compensator
      the dose was non-uniform. Contrarily, the average dose homogeneity with rice
      compensator was measured within +/- 5%, except for the thorax region. Partial
      lung block can reduce the dose which the lung received. This is a simple method
      to improve the dose homogeneity and to reduce the lung dose received. The
      compensator-rice is cheap, and acrylic boxes are easy to obtain. Therefore, this
      technique is suitable for more studies.

PMID- 11573796
TI  - Automated synthesis of 16alpha-[18F]fluoroestradiol-3,17beta-disulphamate.
AB  - After 16alpha-[15F]fluoroestradiol ([18F]FES) has been successfully prepared in
      an automated module, the synthesis of 16alpha-[18F]fluoroestradiol-3,17beta
      disulphamate ([18F]FESDS) is described as a module-assisted one-pot procedure
      which can provide 10GBq [18F]FESDS with a radiochemical purity better than 99%.
      The procedure is reliable and reproducible and requires a time of about 90 min.
      Because of its high sulphatase-inhibitory effect [15F]FESDS is thought to be a
      new PET tracer to image sites of high sulphatase activity.

PMID- 11573797
TI  - A technetium-99m-labelled cyclam acid porphyrin (CAP) for tumour imaging.
AB  - A new water-soluble cyclam acid porphyrin (CAP), 5,10,15,20-tetrakis [4
      [4',8',11'-tris(carboxymethyl)-1'-(1',4',8',11'
      tetraazacyclotetradecane)amidomethyleneoxy]phenyl] porphyrin has been
      synthesised, characterised and labelled with 99mTc. In vivo distribution studies
      were performed in C6-gliomas and N-nitroso-N-methylurea (NMU) induced mammary
      tumour bearing rats and scintiimages were obtained at 5 h post-administration of
      the labelled ligand using gamma camera computer system. Tumour to muscle (T/M)
      ratios were determined and compared with currently available tumour seeking
      radiopharmaceuticals such as 99mTc(V)-DMSA, 99mTc-Citrate and 201TlCl. In the
      case of NMU induced mammary tumour rats the ratios were 6.93, 1.97, 5.30 and
      3.29; while in the case of C6-gliomas the ratios were 5.58, 2.18, 3.96 and 3.02
      for 99mTc-CAP, 99mTc(V)-DMSA, 99mTc-Citrate and 203TlCl, respectively.

PMID- 11573798
TI  - Technetium-99m direct radiolabeling of lanreotide: a somatostatin analog.
AB  - Lanreotide, a synthetic octapeptide analog of a native hormone somatostatin, was
      labeled with a commonly available, inexpensive radionuclide 99mTc. Labeling was
      accomplished by reduction of the cysteine bridge, which provided sulfhydryl
      groups for chelation with 99mTc. Stannous chloride was used as reducing agent,
      while tartrate acted as transchelating agent. Lanreotide (100 microg), stannous
      chloride dihydrate (100 microg) and tartaric acid (64 microg) were dissolved in
      acetate/acetic acid buffer (pH 2.8). After overnight (approximately 18 h)
      incubation, approximately 444 MBq (12 mCi) 99mTc was added and kept in boiling
      water for 30 min. More than 97% labeling efficiency was confirmed by RP-HPLC,
      ITLC-SG and C18 cartridge analysis. Radiolabeling results in one major peak when
      analyzed by reverse-phase HPLC. The stability of the 99mTc-peptide bond was
      evaluated by cysteine challenge studies.

PMID- 11573799
TI  - Pre-concentration and measurement of low levels of gamma-ray emitting
      radioisotopes in coastal waters.
AB  - We describe extensive testing of a large-volume, high-speed water sampler for the
      concentration and measurement of radionuclides using high-resolution gamma ray
      spectrometry. The sampler processed hundreds to thousands of liters of natural
      waters with variable suspended sediment and salinity loads at flow rates of 10
      201/min. Extraction of most radionuclides in the water column was accomplished
      through the combination of physical filtration down to 0.1 microm particle size
      and chemical separation of dissolved species on cellulose-based inorganic sorbent
      beds without recourse to complex, or hazardous chemistry. Performance and
      extraction efficiencies for suites of radioisotopes were determined in the
      laboratory and in the field with river and coastal ocean water samples.
      Extraction and recovery efficiencies are better than 90% for most fission and
      activation product radioisotopes. This methodology has broad application to the
      study of the distribution and fate of radioisotopes in coastal waterways.

PMID- 11573800
TI  - Breakthrough of 225Ac and its radionuclide daughters from an 225Ac/213Bi
      generator: development of new methods, quantitative characterization, and
      implications for clinical use.
AB  - Bisumth-213, a short-lived alpha particle emitting radionuclide, is generated
      from the decay of 225Ac, which has a half-life of 10 days. The development of a
      clinical 225Ac/213Bi generator and the preparation of a 213Bi radiolabeled
      antibody for radioimmunotherapy of leukemia have been reported. The 225Ac decay
      scheme is complex; therefore a thorough understanding of the impact of both the
      parent 225Ac and its daughters on radiolabeling, purification, and quantification
      is necessary for optimal use of the generator system. This paper reports: (i)
      unique new methods to measure 221Fr, 213Bi, and 209Pb, the prominent daughters of
      225Ac; and (ii) a quantitative evaluation of 225Ac/213Bi generator breakthrough
      and the radionuclidic purity of 213Bi labeled radiopharmaceutical dose
      formulations. A quantitative multi-dimensional proportional scanning method was
      employed to distinguish and measure specific daughter radionuclides. This method
      combines thin layer chromatography in two perpendicular directions with
      attenuated collimation as a function of time for data collection and analysis.
      Francium-221 and 213Bi eluted differentially from the generator, and 221Fr
      contributed minimally to unchelated 213Bi in the reaction and final products.
      Lead-209 was present in the reaction solution, but not strongly bound by the
      chelating moiety either (i) under the 213Bi labeling reaction conditions or (ii)
      following chelated 213Bi decay. As a consequence of incorporating several new
      procedures to the operation of the generator, 225Ac breakthrough in the final
      product was further reduced and represented a trivial contaminant in the final
      drug formulations.

PMID- 11573801
TI  - The response of a thermoluminescent dosimeter to low energy protons in the range
      30-100 keV.
AB  - This study demonstrates the thermoluminescence (TL) response of CaF2:Tm
      (commercial name TLD-300) to 30-100 keV protons which were generated by means of
      a Cockcroft-Walton accelerator. The phenomenon in which the total
      thermoluminescent output from CaF2:Tm (TLD-300) decreases with proton energy from
      30 to 100 keV (with increase of LET) can be interpreted by the track structure
      theory (TST). The analysis of the glow peaks: P2 (131 degrees C), P3 (153.5
      degrees C) and P6 (259 degrees C), of TLD-300 show the oscillatory decreasing
      phenomenon as a function of incident proton energy, which can be interpreted with
      the TST and the oscillatory emission of electrons in a thermoluminescent
      dosimeter (TLD) that is caused by resonant or quasi-resonant charge transfer in
      ion-atom interactions in this TLD-300.

PMID- 11573802
TI  - Propagation of uncertainties in sample properties to the uncertainty of the
      counting efficiency in gamma-ray spectrometry.
AB  - Explicit expressions are derived describing the variance of the counting
      efficiency for a homogeneous cylindrical sample, placed coaxially on the
      detector's symmetry axis, in terms of the variances of the sample properties
      thickness, density and composition. In the derivation, the emission of gamma-rays
      parallel to the sample axis and the efficiency for an area source proportional to
      the solid angle subtended by the source from the effective point of interaction
      of the gamma-rays within the detector crystal are assumed. For the uncertainties
      of the mass attenuation coefficients, as well as for the uncertainties of
      concentrations of admixtures to the sample matrix, constant relative
      uncertainties are assumed.

PMID- 11573803
TI  - Use of neutron reflection method to assay nuclear materials in solutions.
AB  - Neutron reflection methods are used in the chemical analysis of bulk samples,
      especially for the determination of contents in hydrogenous solutions. In these
      techniques albedo is measured by measuring either the activation of a foil, or
      count rate from a neutron detector. In the present paper Monte Carlo simulations
      are performed using this method for the possibility of detecting inadvertent
      criticality in the reprocessing plants and also estimation of 10B in heavy water,
      which is used as a moderator in PHWRs.

PMID- 11573804
TI  - Self-absorption correction for gamma spectrometry of powdered milk samples using
      Marinelli beaker.
AB  - Self-absorption was measured for the activity calculation of the 1460.8 and
      2614.47 keV lines of the 40K and the 208Tl, respectively, in powdered milk
      samples. Five Marinelli beakers were prepared with powdered milk in different
      degrees of compaction and the spectra were measured with an HPGe detector. The
      detection efficiency versus density was obtained and the self-absorption
      correction factors versus density were calculated for powdered milk. The results
      obtained show that this factor must be considered in the calculations of
      activities.

PMID- 11573805
TI  - Elimination of the background signal in tooth enamel samples for EPR-dosimetry by
      means of physical-chemical treatment.
AB  - A method of elimination of the background EPR signal in tooth enamel is proposed.
      This method implies treatment of enamel powder by highly active reduction reagent
      hydrazine with subsequent washing out by ethanol-water solution. Such treatment
      results in reducing both the native background signal (which is assumed to be
      originated by the organic component) and the mechanical induced EPR signal in
      enamel. Testing of the efficiency of hydrazine treatment is made for different
      sizes of enamel powder. It is shown that the optimal results are obtained for a
      powder fraction of about 100-200 microm. The radiation-induced EPR signal in
      enamel is practically not changed after treatment by hydrazine.

PMID- 11573806
TI  - Bronchial dosimeter for radon progeny.
AB  - A true bronchial dosimeter has been designed, consisting of four 400-mesh wire
      screens and a filter paper. With a face velocity of 3.3 cm s(-1) for home
      exposure and 4.6 cm s(-1) for mine exposure, the deposition pattern on the wire
      screens were found to satisfactorily match the variation of the dose conversion
      factor (in units of mSv WL M(-1)) with the size of radon progeny from 1 to 1000
      nm. In this way, the bronchial dosimeter directly gives bronchial dose from the
      alpha counts recorded on the wire-screens and the filter paper. Calculations of
      the dose conversion coefficient (DCC) using the proposed bronchial dosimeter and
      the lung dosimetric model were performed for typical aerosol characteristics.
      Values obtained from the bronchial dosimeter yielded overestimates of the DCC by
      11.1% and 2.4% for typical home and mine conditions, respectively.

PMID- 11573807
TI  - 129I in lakes of the Chernobyl fallout region and its environmental implications.
AB  - We present seasonal results of 129I in fresh-water lakes located in central
      Sweden, an area over which the amount of fallout deposition from the Chernobyl
      accident varied significantly (2-120 kBq/m2 for 137Cs). 129I concentrations in
      the lakes ranged from 2.1 to 15.0 x 10(8) atoms per liter and did not show
      elevated concentration in lakes located in regions of high Chernobyl fallout.
      Apparently, the studied region is strongly influenced by 129I releases from the
      reprocessing facilities through precipitation. Desorption or resuspension of 129I
      from soils and sediments does not seem to be an active process to increase the
      concentration of 129I in the lakes.

PMID- 11573808
TI  - Factor analysis applied to distribution of elements in western Turkey.
AB  - This paper examines the results of R-mode factor analysis performed on four
      radionuclides and two elements data from a geochemical survey from western
      Turkey. Sediment and soil samples numbering 321 were collected along the Gediz
      river and analysed for 238eU, 232eTh, 40K, 226Ra, Mg and Pb. Two factors in soil
      and sediment, which account for 59% and 56% of the total variance, respectively,
      were extracted and named as geological structure and volcano.

PMID- 11573809
TI  - Origin and subsurface history of geothermal water of Murtazabad area, Pakistan-
      an isotopic evidence.
AB  - The Murtazabad area represents one of the major geothermal fields in Pakistan,
      with seven hot springs lying along the Main Karakoram Thrust. Discharge of the
      springs is 50-1200 l per minute with the surface temperature from 40 to 94
      degrees C. Environmental isotopes and chemical concentrations have been used to
      investigate the origin and subsurface history of thermal water. Four sets of
      water samples were collected and analyzed for various isotopes including 18O, 2H
      and 3H of water; 34S and 18O of dissolved sulphates and chemical contents.
      Isotopic and chemical data show that the origin of thermal water is meteoric
      water. On the delta-diagram, delta18O and delta2H data plotting below the local
      meteoric water line with a slope around 12.3 show that the original thermal water
      receives recharge from precipitation at higher altitude (3000 m) and undergoes
      delta18O shift of about 1 per thousand due to exchange with rocks. Different
      correlations between isotopes, temperature and Cl indicate that the observed
      isotopic compositions have evolved due to mixing of different proportions of
      shallow water at different spring paths during movement of thermal water towards
      the surface. It is also inferred from the tritium data along with delta18O and
      delta2H that the circulation time is long and is estimated to be more than 50
      years.

PMID- 11573810
TI  - Natural gamma-radiation in the Aeolian volcanic arc.
AB  - Pulse-height distributions of gamma-rays, obtained with a field NaI(Tl)
      scintillation spectrometer in numerous sites of the Lipari and Vulcano islands
      (Aeolian volcanic arc, Italy), were measured to determine the U, Th and K
      concentrations of the bedrock and the relative values of the air absorbed dose
      rate. U is spatially related to both Th and K and the Th/U ratio is on average
      3.1-3.5. The magmatic evolution is reflected by the concentration of the three
      radioelements, as they are more abundant within the more felsic units of the
      volcanic series. The higher values of U (15.7-20.0 ppm) coincide with higher Th
      (48.3-65.9 ppm) and K (4.9-6.1%) concentrations associated with rhyolitic rocks
      of the third cycle (< 50 ky). The air absorbed dose rate varies from 20 to 470
      nGy h(-1). The highest values (> 350 nGy h(-1)) are observed on outcrops of
      rhyolitic obsidian lava flows. The cosmic-ray contribution is also evaluated to
      estimate the total background radiation dose rate.

PMID- 11573811
TI  - An in vitro model for murine ureteric epithelial cells.

PMID- 11573812
TI  - Polyunsaturated fatty acids are not essential for survival and proliferation of a
      human B cell line.

PMID- 11573813
TI  - Nonviral gene transfer into primary cultures of human and porcine mesothelial
      cells.
AB  - Due to their abundance and accessibility, mesothelial cells may be suitable tools
      for recombinant reagent expression by gene transfer. Genetically modified porcine
      mesothelial cells (PMCs) may have the potential for the treatment of vascular
      diseases in humans. We studied the effect of various transfection reagents on the
      primary culture of PMCs and human mesothelial cells (HMCs). The cells were
      transfected with a plasmid encoding a reporter gene (luciferase or green
      fluorescent protein [GFP]) under the control of the cytomegalovirus promoter.
      Transfection was achieved using cationic lipids (DOSPER and DOTAP) or calcium
      phosphate/deoxyribonucleic acid coprecipitation or Fugene 6. Results showed that
      Fugene 6 was the most efficient and reproducible transfection reagent with both
      PMCs and HMCs. With Fugene 6, luciferase activity in PMCs (1.5 x 10(8) relative
      light units [RLU]/10(6) cells) was at least 2.5-fold higher than with the other
      transfection reagents, and it was 100-fold higher than in HMCs. However, the
      proportion of transfected cells expressing GFP was only 1%. These preliminary
      findings open up new avenues for developing experimental studies on the use of
      genetically modified PMCs.

PMID- 11573814
TI  - Isolation of endothelial cells from human placental microvessels: effect of
      different proteolytic enzymes on releasing endothelial cells from villous tissue.
AB  - Approaches for the isolation of human placental microvascular endothelial cells
      (HPMEC) using proteolytic enzymes have been described recently. However, the
      isolation procedure and enzyme composition most suitable for optimal
      disaggregation of placental tissue and isolation of HPMEC has not yet been
      established. We tested different proteolytic enzymes and enzyme mixtures for
      their capabilities of releasing endothelial cells from human term placental
      villous tissue. Best results were obtained with a mixture of
      collagenase/dispase/deoxyribonuclease I (0.28%/0.25%/0.01%). By adding a
      discontinuous Percoll gradient centrifugation step to the enzymatic dispersion,
      about 1 x 10(6) cells/g tissue with more than 30% von Willebrand factor (vWf)
      positive cells were obtained. However, the total cell number and number of vWf
      positive cells were highly dependent on the lot of collagenase used. A perfusion
      step prior to mincing of villous tissue did not increase the amount of vWf
      positive cells. We conclude that the methods described in this study are suitable
      to isolate high yields of HPMEC and that the composition of the collagenase
      preparation is crucial to the successful release of endothelial cells from
      placental tissue. To obtain pure HPMEC, further separation steps, e.g., cell
      sorting with antibodies against endothelial specific cell surface antigens are
      necessary.

PMID- 11573815
TI  - Cell motility in a new single-cell wound model.
AB  - Until now researchers have used a monolayer of cultured cells to investigate cell
      motility toward an injured cell. However, we suspect that, when using this
      method, adjacent cells move to the free space due to relief of contact
      inhibition. The current study was designed to investigate the cell motility
      nearby an injured cell in varying cell connectivity. A low-power laser beam was
      used to damage one cell selectively with the silver coating beads. After injury,
      we observed the cell motility in three different cell types: (1) those
      immediately adjacent to the injured cell, (2) those removed from the injured cell
      by interposition of another cell, and (3) those removed from the injured cell by
      free space. The cells that are in direct contact with the injured cell moved
      toward the injured cell within 1.5-3.0 h. Indirectly connected cells and cells
      with no contact, on the other hand, showed no significant movement toward the
      injured cell. This suggests that the cell motility toward the cell injury is not
      only due to relief of contact inhibition but might also be caused by cell-to-cell
      signaling via cell connection. The current method will provide a tool to create a
      cell injury without damaging adjacent cells.

PMID- 11573817
TI  - Analysis of three marine fish cell lines by rapd assay.
AB  - We tested the applicability of the random amplified polymorphic deoxyribonucleic
      acid (RAPD) analysis for identification of three marine fish cell lines FG, SPH,
      and RSBF, and as a possible tool to detect cross-contamination. Sixty commercial
      10-mer RAPD primers were tested on the cell lines and on samples collected from
      individual fish. The results obtained showed that the cell lines could be
      identified to the correspondent species on the basis of identical patterns
      produced by 35-48% of the primers tested; the total mean similarity indices for
      cell lines versus correspondent species of individual fish ranged from 0.825 to
      0.851, indicating the existence of genetic variation in these cell lines in
      relation to the species of their origin. Also, four primers, which gave a
      monomorphic band pattern within species/line, but different among the
      species/line, were obtained. These primers can be useful for identification of
      these cell lines and for characterization of the genetic variation of these cell
      lines in relation to the species of their origin. This supported the use of RAPD
      analysis as an effective tool in species identification and cross-contamination
      test among different cell lines.

PMID- 11573816
TI  - Expansion and long-term culture of differentiated normal rat urothelial cells in
      vitro.
AB  - The objective of this study is to establish a reliable cell culture system for
      the long-term culture of rat urothelial cells (RUC), in which the cells multiply
      in vitro and form stratified polarized urothelium. Urothelial cells were
      harvested by the enzymatic digestion of the urothelium exposed by the eversion of
      resected rat bladders. Primary cultures were initiated in keratinocyte serum-free
      medium (KSFM) for selective proliferation of urothelial cells. Subsequently, the
      cells were propagated in a mixture of conditioned medium (CM) derived from Swiss
      3T3 cell culture supernatant and KSFM (CM-KSFM). Mean population doubling time
      was 13.8 +/- 0.9 h. RUC were successfully maintained for 18 passages over a
      period of 4-5 mo. Detailed investigations of culture conditions showed that CM
      KSFM yielded a differentiated multilayer structure. The stratified urothelial
      sheets measuring 4 x 6 cm2 could be formed and then detached using dispase.
      Cytokeratin pattern in both the cultured urothelial monolayer and engineered
      stratified layers was similar to those seen in vivo, as assessed with monoclonal
      antibody against cytokeratin 17. Ultrastructural morphology showed microvilli,
      basal cell layer, and desmosomes between adjacent cells in the stratified
      urothelium.

PMID- 11573818
TI  - Production of bioengineered cancer tissue constructs in vitro: epithelium
      mesenchyme heterotypic interactions.
AB  - A few models have been established to study cancer cells in vitro. However, the
      cellular interactions have rarely been studied specifically using bioengineered
      cancer constructs combining human carcinoma cells and tumor-associated
      fibroblasts. We developed an in vitro model of tridimensional bioengineered
      cancer tissue constructs (bCTC) by seeding mammary epithelial cancer cells or
      normal keratinocytes over a mesenchymal layer containing tumor-derived
      fibroblastic cells or normal skin fibroblasts. After the introduction of
      epithelial cells, each construct was cultured for another 10 d. Histologic
      analyses showed that carcinoma cell lines could invade the subjacent mesenchymal
      layer and that the capacity to migrate was related to the invasive potential of
      cancer cells and the type of fibroblasts used, while noninvasive populations did
      not. Of the tested epithelial cells, MDA-MB-231 and, to a lesser degree, HDQ-P1
      cell lines were invasive, and the invasion was deeper into the mesenchymal
      component containing tumor-derived fibroblasts. However, with normal skin
      fibroblasts, the mesenchymal layer was degraded twice faster than with tumor
      derived fibroblastic cells. MDA-MB-231 cells and normal keratinocytes induced the
      highest level of gelatinase B, and the level was lowest with the MCF-7 cell line.
      The activated form of gelatinase B was, however, induced to the highest levels in
      the keratinocyte-seeded bCTC containing tumor-derived but not normal fibroblasts.
      MDA-MB-231 was the only epithelial cancer cell line whose activity of gelatinase
      A was reduced when cocultured with tumor-derived fibroblasts but not under normal
      fibroblast stimulation. Finally, a 50/48-kDa gelatinase band has been observed in
      bCTCs with noninvasive epithelial cells only. Our study demonstrates the
      selective secretion of gelatinases according to the phenotype of the cells seeded
      in the various bCTCs.

PMID- 11573820
TI  - An in vitro method for recording the electrical activity of the isolated heart of
      the adult Drosophila melanogaster.
AB  - A recording chamber for monitoring the electrophysiological properties of the
      isolated heart of adult Drosophila melanogaster has been developed. Spontaneously
      generated field potentials of constant amplitude can be recorded for 6-8 h (n =
      14); in very few cases, records were maintained stable for over 10 h (n = 4), and
      in some cases below 6 h (n = 5). The chamber consists of the tip of a
      micropipette, which allows for monitoring the field potential generated by the
      spontaneously contracting heart. The method can produce accurate information
      about the heart rate and the amplitude of the cardiac action potential. The
      preparation can be used for pharmacological studies on the heart of D.
      melanogaster since it responds, with an increase in the heart rate, to unusually
      low concentrations of octopamine, 1 nM, a compound with cardioaccelerating
      properties for insect heart. The recording system can be easily modified for
      experiments on the heart of other insects. Finally, the isolated heart of D.
      melanogaster provides a simple method for identifying mutations that affect heart
      physiology.

PMID- 11573819
TI  - Effects of fibroblast growth factor 2 and insulin-like growth factor II on the
      development of parthenogenetic mouse embryos in vitro.
AB  - Most parthenogenetic embryos (PEs) in mammals die shortly after implantation, and
      this failure to develop is associated with genomic imprinting. We have examined
      the influence of human recombinant basic fibroblast growth factor 2 (FGF-2) and
      human recombinant insulin-like growth factor II (ICF-II) on the development of
      (CBA x C57BL/6)F1 parthenogenetic mouse embryos. Embryos were treated in vitro at
      the morula stage with different doses of FGF-2 and, after their development to
      blastocysts, transferred to pseudopregnant recipients. The optimal doses of FGF-2
      did not affect the number of forming and implanting blastocysts, but increased,
      from 20 to 42%, the number of embryos developing to somite stages. PEs (18-21
      somites) treated with an optimal dose of FGF-2 were explanted for further
      development in culture by treatment with the second growth factor, IGF-II. Eighty
      three percent of those embryos cultured with IGF-II (2.5 microg/ml) developed to
      35 or more somites, as compared with 36% of embryos cultured without any growth
      factors (P < 0.01). Also, a significantly higher proportion of PEs developed to
      40-50 somites in this case. These results show that the in vitro treatment of PEs
      with FGF-2 at the morula stage increases the number of somite embryos, and the
      second treatment of somite PEs with IGF-II in culture medium prolongs their
      development significantly.

PMID- 11573821
TI  - Differing sensitivity of tumor cells to apoptosis induced by iron deprivation in
      vitro.
AB  - We studied the sensitivity of tumor cells to the induction of apoptosis by iron
      deprivation. Iron deprivation was achieved by the employment of a defined iron
      deficient culture medium. Mouse 38C13 cells and human Raji cells die within 48
      and 96 h of incubation in iron-deficient medium, respectively. On the contrary,
      mouse EL4 cells and human HeLa cells are completely resistant to the induction of
      death under the same experimental arrangement. Deoxyribonucleic acid
      fragmentation analysis by agarose gel electrophoresis as well as flow cytometric
      analysis after propidium iodide staining detected in 38C13 and Raji cells, but
      not in EL4 and HeLa cells, changes characteristic to apoptosis. The 38C13 cells,
      sensitive to iron deprivation, also displayed a similar degree of sensitivity to
      apoptosis induction by thiol deprivation (achieved by 2-mercaptoethanol
      withdrawal from the culture medium) as well as by rotenone (50 nM), hydroxyurea
      (50 microM), methotrexate (20 nM), and doxorubicin (100 nM). Raji cells shared
      with 38C13 cells a sensitivity to rotenone, methotrexate, doxorubicin, and, to a
      certain degree, to hydroxyurea. However, Raji cells were completely resistant to
      thiol deprivation. EI4 and HeLa cells, resistant to iron deprivation, also
      displayed a greater degree of resistance to most of the other apoptotic stimuli
      than did their sensitive counterparts. We conclude that some tumor cells in vitro
      are sensitive to apoptosis induction by iron deprivation, while other tumor cells
      are resistant. All the tumors found to be sensitive to iron deprivation in this
      study (four cell lines) are of hematopoietic origin. The mechanism of resistance
      to apoptosis induction by iron deprivation differs from the mechanism of
      resistance to thiol deprivation.

PMID- 11573822
TI  - Mutations in the human homologue of the Drosophila segment polarity gene patched
      in oral squamous cell carcinoma cell lines.
AB  - In the present study, we have analyzed tumor deoxyribonucleic acid from oral
      squamous cell carcinoma (OSCC) cells for patched mutations using an exon-by-exon
      single strand conformation polymorphism assay and direct sequencing. We found two
      missense mutations which affected the conserved residue in the transmembrane
      domains of the gene product and in the intracellular loop at the C-terminal
      residue implicated in regulating the smoothened molecule. In addition, we
      demonstrated that the N-terminal fragment of sonic hedgehog (Shh-N) stimulates
      the growth of normal epithelial cells, the OSCC cell line, NA, and the salivary
      gland adenocarcinoma cell lines, HSG and HSY, which have no detectable mutation
      in patched. On the other hand, Shh has no effect on human SCC cells (UE, KA, KO,
      NI, A431 cells) that have mutations in patched. These results strongly suggest
      that an Shh-patched signaling is involved in the cell growth of oral epithelial
      cells and in the tumorigenesis of OSCCs.

PMID- 11573824
TI  - Dysfunctional ischaemic myocardium: implications of regional flow-function
      relations.

PMID- 11573823
TI  - Identification of a region on the adenovirus E1A gene responsible for induction
      by phorbol ester tumor promoter.
AB  - 12-O-Tetradecanoylphorbol-13-acetate (TPA) treatment induces human adenovirus
      (Ad) early region 1A (E1A) messenger ribonucleic acid expression in infected or
      Ad-transformed cells. Here, we report that deletion analysis has identified a TPA
      responsive element (TRE) in the E1A enhancer region. Deletion analysis indicates
      that the TRE is located upstream of the E1A cap site between nucleotides -237 and
      -47. Incubation of extracts from TPA-treated cells with radioactively labeled
      deoxyribonucleic acid (DNA) fragments containing the TRE (-237 to -47) form
      specific DNA-protein complexes as demonstrated by gel shift analysis and
      Southwestern blotting. These experiments provide evidence that novel protein-DNA
      complexes are formed on a region of the E1A promoter required for TPA-enhanced
      expression. We speculate that these DNA-binding proteins may interact with the
      TRE and play a critical role in the mechanism through which TPA upregulates
      transcription from the Ad E1A gene.

PMID- 11573825
TI  - Thrombolysis in myocardial infarction in a prospective cohort of 2,515
      consecutive patients: older age and longer delays lead to a lower thrombolysis
      rate.
AB  - OBJECTIVE: This prospective study sought to determine the rate of thrombolysis in
      myocardial infarction and the factors that influenced it in everyday practice.
      METHODS AND RESULTS: Data were prospectively collected in all patients admitted
      in all (48) university, community, and private hospitals in three departments in
      the Rhjne-Alpes region in France between September 1, 1993 and January 31, 1995.
      Data from 2,515 patients were included. Overall, 36% of the patients received
      thrombolysis. The decrease of the thrombolysis rate with age was very regular.
      The difference between men and women disappeared almost completely when age was
      taken into account in a bivariate analysis. Among 19 variables introduced in the
      logistic regression, only the following ones were significant predictors (odds
      ratio < 1 means less thrombolysis): age (odds ratio: 0.60 per decade),
      administrative department, type of hospital (community/tertiary: 0.74;
      private/tertiary: 0.58), history of myocardial infarction or of angina pectoris
      (0.67), location of myocardial infarction (Q wave non anterior/Q wave anterior:
      0.75; non Q wave/Q wave anterior: 0.18), delay between symptoms onset and first
      medical intervention (0.06), history of cancer (0.47), and history of psychiatric
      disorder (0.38). CONCLUSIONS: In France as in other countries, the rate of
      thrombolysis is low. In order to increase this rate, we have to find ways to be
      more "aggressive" in older patients, and to precisely describe the health care
      pathways in order to shorten delays.

PMID- 11573826
TI  - Serum and ascites fluid cytokine levels in patients with chronic heart failure.
AB  - OBJECTIVE: Cytokines that are capable of modulating cardiovascular function were
      reported to be elevated in patients with advanced heart failure. We evaluated the
      diagnostic importance of cytokines both in the serum and ascites. MATERIAL AND
      METHODS: We determined serum and ascites fluid TNF-alpha, IL-1beta, IL-6, IL-8,
      and soluble IL-2 receptor levels in 14 patients with congestive heart failure
      (group 1) and in 15 patients with chronic liver disease (group 2). RESULTS:
      Ascites fluid IL-8 and soluble IL-2 receptor levels were found to be
      significantly elevated in group 1 when compared with group 2 (p = 0.014 and p =
      0.005). There were no statistical differences in serum TNF-alpha, IL-1beta, IL-6,
      IL-8, and soluble IL-2 receptor levels and ascites fluid TNF-alpha, IL-1beta, and
      IL-6 levels. Ascites fluid/serum IL-1beta and IL-8 ratio was lower in group 1
      when compared with group 2 (p = 0.001 and p = 0.005). Ascites fluid/serum IL-2
      and IL-6 ratio was higher in group 1 when compared with group 2 (p = 0.035 and p
      = 0.025). CONCLUSION: Cytokine levels in ascites fluid, but not in serum, are
      important in congestive heart failure. Ascites fluid/serum cytokine level ratios
      were detected to be more conclusive and valid in the diagnosis work-up of ascites
      aetiology.

PMID- 11573827
TI  - Current thinking in statin therapy.
AB  - The HMG-CoA reductase inhibitors (statins) are now considered the most potent
      lipid-lowering drugs. Treatment with statins reduces both morbidity and mortality
      rates due to coronary artery disease. There is now increasing evidence that the
      clinical benefits obtained with statins cannot be solely attributed to a decrease
      in low-density lipoprotein (LDL) level. These drugs may also have beneficial
      effects on endothelial dysfunction, LDL oxidation, rheological and thrombogenic
      factors, cellular inflammation and plaque formation and stability. Further, there
      are differences among the various statins on these non-lipid variables. The
      biochemical effects of statins, as well as their clinical benefits, should be
      taken into consideration.

PMID- 11573828
TI  - Clinical and echocardiographic assessment of a right-to-left shunt across an
      atrial septal defect secondary to tricuspid regurgitation.
AB  - OBJECTIVE: Cyanosis in conjunction with atrial septal defect does not necessarily
      indicate the Eisenmenger syndrome. Exceptionally, the right-to-left shunt may
      result from tricuspid regurgitant flow and its unusual direction. METHODS: We
      describe thirteen patients with atrial septal defect and accompanying tricuspid
      regurgitation. In all of them, the tricuspid regurgitant jet was oriented towards
      the interatrial septum. This was found on the basis of echocardiographic
      examination and subsequent frame-by-frame analysis of videotape. RESULTS: Of
      thirteen patients, cyanosis was observed in 7 (53%). Among those seven, three had
      moderate pulmonary hypertension (pulmonary artery systolic pressure (PASP)
      between 40 and 60 mm Hg). The remaining four patients with marked pulmonary
      hypertension (PASP > 60 mm Hg) underwent cardiac catheterization, which
      demonstrated low values of pulmonary artery resistance. Except for the one
      patient with a history of the cerebral embolic event, all were qualified for
      cardiac surgery. In the postoperative observation they were uneventful and showed
      clinical recovery and echocardiographic improvement. CONCLUSIONS: Appreciable
      arterial desaturation and cyanosis in patients with ASD, regarded as
      uncomplicated, should be followed by careful investigation for the direction of
      tricuspid regurgitant flow.

PMID- 11573829
TI  - Usefulness of coronary angiography for assessing left ventricular systolic
      function.
AB  - OBJECTIVE: In previous echocardiographic studies, a correlation between ejection
      fraction of the left ventricle and change in the movement of the mitral annular
      ring was found. In the light of these studies, we planned to investigate the
      relationship between systolic shortening (SS) and percent of systolic shortening
      (PSS), calculated from the long axis frame in coronary angiography and left
      ventricular systolic function. METHODS AND RESULTS: One hundred and thirty-eight
      patients (40 men and 98 women; mean age 58 +/- 10 years) who had been referred
      for coronary angiography and left ventriculography were included in the study.
      Ejection fraction (EF) was calculated from left ventriculography obtained from 30
      degrees right anterior oblique projection. Distance from the lower border of the
      ostium of the left coronary artery to the most apical border of the left anterior
      descending (LAD) artery was measured at end-systole (ES) and end-diastole (ED)
      using coronary angiography obtained from the same projection. SS as ED-ES and PSS
      as SS/ED were calculated. Correlation of SS and PSS with EF was calculated (EF =
      13.7 + 4.8 x SS, r = 0.91, p < 0.001 and EF = 14.2 + 6.5 x PSS, r = 0.90, p <
      0.01). SS < 7 mm (criterion A) and PSS < 6% (criterion B) suggested that left
      ventricle EF was less than 50%, with a sensitivity, specificity and diagnostic
      accuracy of 83%, 100%, 95%; 95%, 86% and 88%, respectively. CONCLUSION: SS and
      PSS highly significantly correlate with left ventricular EF. Therefore, left
      ventriculography could be omitted in selected patients undergoing coronary
      angiography if it is not necessary to define the anatomic structure of the left
      ventricle.

PMID- 11573830
TI  - Serum uric acid for short-term prediction of cardiovascular disease incidence in
      the Gubbio population Study.
AB  - OBJECTIVE: The Gubbio Study is an Italian population study measuring risk factors
      for and incidence of major cardiovascular diseases. This analysis investigates
      the association of serum uric acid with the incidence of coronary and
      cardiovascular events. METHODS: A population sample of 2469 men and women aged 35
      74 years, free from major cardiovascular diseases and in whom serum uric acid was
      measured in 1983 along with other standard risk factors, were followed up for 6
      years and the incidence of coronary heart disease (CHD) and all cardiovascular
      atherosclerotic (CVD) events, both fatal and non-fatal, was computed.
      Proportional hazards models were used for the prediction of these events.
      RESULTS: In six years 61 CHD hard criteria, 109 CHD any criterion and 149 CVD
      events were recorded. Age-adjusted rates per 1000 of the 3 event categories were
      computed in sex-specific quintiles (Q) of serum uric acid with 428 +/- 76 (Q5)
      and 198 +/- 42 (Q1) micromol/l, respectively. Although higher rates were seen in
      Q5 as compared to Q1 for all three first event categories considered (relative
      risks 6.2, 3.6 and 3.7, respectively), a statistically significant trend was seen
      only for CVD all criteria (t = 3.63, p < 0.036). These trends were borderline
      significant for CHD any criterion (t = 2.92, p < 0.06) and not significant for
      CHD hard criteria (t = 2.23, p < 0.11). In multivariate models, adjusted for 8
      other risk factors, serum uric acid showed a statistically significant
      contribution to predict CVD incidence [relative risk (RR) for 92 micromol/l
      difference of 1.24 with 95% confidence intervals (CI) 1.05-1.45], whereas the
      statistical contribution to predict CHD any criterion (RR = 1.19 with CI 0.98
      1.45) and CHD hard criteria (RR = 1.20 with CI 0.93-1.55) was not significant.
      Diuretic treatment and blood urea, as further confounders, were positively and
      significantly related to event incidence (RR ranging from 1.21 to 2.00) but serum
      uric acid maintained its independent and statistically significant role in the
      prediction of CVD events (RR = 1.18 with CI 1.00-1.39). Presence of specific
      treatments to lower serum uric acid levels (in 1.13% of the population), tested
      as final confounders, was not statistically contributory. CONCLUSIONS: Increased
      serum uric acid levels are independently and significantly associated with risk
      of CVD events in the 6-year follow-up of the Gubbio Study. Longer follow-up is
      needed before the contributory role of serum uric acid can be properly assessed
      to explain CHD incidence.

PMID- 11573831
TI  - Multisite cardiac pacing. A proposal for a simple code.

PMID- 11573832
TI  - Severe, but completely reversible heart failure in an adult with meningococcal
      sepsis.
AB  - A 25-year-old woman developed meningococcal septicaemia, among others complicated
      by a combination of cardiogenic and distributive shock requiring full
      haemodynamic support in the acute phase. Besides clinical course and treatment in
      the acute phase, we describe treatment in the recovery phase and make some
      comments concerning the pathophysiology. This case demonstrates the importance of
      intensive treatment for cardiac failure in the initial period and long-term
      therapy afterwards because myocardial function can be fully restored.

PMID- 11573833
TI  - A unique double right coronary artery abnormality.
AB  - Double right coronary artery is a very rare coronary artery abnormality. Two
      cases have been reported so far. In these cases, both right coronary arteries
      were giving the same branches, and originated from the same orifice. In our case,
      both right coronary arteries were giving different branches. We could not find
      such a case in the literature. Therefore, we consider our case a unique double
      right coronary artery abnormality.

PMID- 11573834
TI  - Right ventricular aneurysm complicating right ventricular infarction.
AB  - Right ventricular (RV) involvement commonly occurs in patients with acute
      inferior myocardial infarction and is associated with high mortality and
      morbidity. RV dysfunction and dilatation commonly recover in survivors; chronic
      RV dyskinesia and failure are rare complications. This case report presents a
      patient in whom an isolated RV aneurysm complicates a RV involvement of acute
      inferior-posterior myocardial infarction.

PMID- 11573835
TI  - Aneurysms and pseudoaneurysms of coronary arteries and saphenous vein coronary
      artery bypass grafts: a case report and literature review.
AB  - Aneurysms or pseudoaneurysms of the native coronary arteries or bypass grafts are
      uncommon and represent a pathology with high morbidity and mortality. We report
      the diagnosis of an aneurysm of a saphenous vein coronary artery bypass graft
      with an atypical presentation and review incidence, modes of presentation,
      aetiology and proposed mechanisms of formation of this and similar entities.
      Complications, diagnostic clues and therapeutic options are also discussed.

PMID- 11573836
TI  - Pregnancy discovery and acceptance among low-income primiparous women: a
      multicultural exploration.
AB  - OBJECTIVES: As part of a larger study exploring psychosocial factors that
      influence self-care and use of health care services during pregnancy, we
      investigated the process of pregnancy discovery and acceptance among a culturally
      diverse group of women who had given birth to their first child in the year
      preceding data collection. METHODS: Eighty-seven low-income women from four
      cultural groups (African American, Mexican, Puerto Rican, and white) participated
      in eight focus groups held in their communities. The focus groups were ethnically
      homogenous and stratified by early and late entry into prenatal care. A social
      influence model guided the development of focus group questions, and the study
      followed a participatory action research model, with community members involved
      in all phases of the research. RESULTS: Issues that emerged from the focus groups
      as possible influences on timing of pregnancy recognition include the role of
      pregnancy signs and symptoms and pregnancy risk perception in the discovery
      process, the role of social network members in labeling and affirming the
      pregnancy, concerns about disclosure, "planning" status of the pregnancy, and
      perceived availability of choices for resolving an unintended pregnancy.
      CONCLUSIONS: The pregnancy discovery process is complex, and when protracted, can
      potentially result in delayed initiation of both prenatal care and healthful
      pregnancy behaviors. Enhancing our understanding of pregnancy discovery and
      acceptance has clear implications for primary and secondary prevention. Future
      research is needed to further explain the trajectory of pregnancy discovery and
      acceptance and its influence on health behaviors and pregnancy outcome.

PMID- 11573837
TI  - Stress and preterm birth: neuroendocrine, immune/inflammatory, and vascular
      mechanisms.
AB  - A growing literature suggests that maternal psychological and social stress is a
      significant and independent risk factor for a range of adverse reproductive
      outcomes including preterm birth. Several issues remain to be addressed about
      stress and vulnerability to stress during pregnancy. Of these, perhaps one of the
      most important questions relates to biologic plausibility. Parturition, the
      process that results in birth, is a biological phenomenon. Very little empirical
      research to date, however, has examined the role of biological processes, if any,
      as mediators of the relationship between stress and preterm birth. In this paper
      we discuss the maternal, placental, and fetal neuroendocrine,
      immune/inflammatory, and vascular processes that may bridge the experience of
      social adversity before and during pregnancy and the biological outcome of
      preterm birth.

PMID- 11573838
TI  - Maternal stress is associated with bacterial vaginosis in human pregnancy.
AB  - OBJECTIVES: Maternal infection, particularly bacterial vaginosis (BV) in
      pregnancy, is one of the leading causes of adverse perinatal outcomes. The
      determinants of individual differences in susceptibility, or vulnerability, to
      maternal infections are poorly understood. This study examines whether chronic
      maternal stress predisposes women to infection during pregnancy, and if so,
      whether the effects of chronic stress on infection are independent of other
      established risk factors. METHODS: We conducted a cross-sectional, clinical
      prevalence study of chronic maternal stress and BV status in a sample of 454
      pregnant women at 14.3+/-0.3 weeks gestation (+/-SEM). BV was diagnosed by Gram
      stain of vaginal fluid samples; chronic maternal stress was assessed using the
      Cohen Perceived Stress Scale. Other established risk factors for BV, including
      maternal age, race/ethnicity, marital status, SES, and behaviors related to
      feminine hygiene, sexual practices, and substance use, were measured using a
      structured interview. RESULTS: Of the 454 women enrolled in this study, 224 (49%)
      were BV positive (Nugent score 7-10), 64 (14%) had intermediate vaginal flora
      (Nugent score 4-6), and 166 (37%) were BV negative (Nugent score 0-3). BV+ women
      had significantly higher chronic stress levels than BV- women (24.6+/-0.5 vs.
      22.2+/-0.6 units (+/-SEM), respectively; t = 3.19; p < .01). Maternal
      sociodemographic variables (African-American race/ethnicity) and behavioral
      characteristics (vaginal douching, number of lifetime sexual partners, and use of
      illicit drugs) also were significantly associated with the presence of BV. After
      controlling for the effects of these variables, using a multivariable logistic
      regression model, chronic maternal stress remained a significant and independent
      predictor of BV status. Women in the moderate-stress group (third quartile) and
      high-stress (fourth quartile) group were 2.3 times (95% CI = 1.2-4.3) and 2.2
      times (95% CI = 1.1-4.2) more likely to be BV+ than women in the low-stress group
      (bottom quartile). CONCLUSIONS: High levels of chronic stress during pregnancy
      are associated with bacterial vaginosis. The effect of chronic maternal stress is
      independent of the effects of other established sociodemographic and behavioral
      risk factors for BV.

PMID- 11573840
TI  - The social context of pregnancy for African American women: implications for the
      study and prevention of adverse perinatal outcomes.

PMID- 11573839
TI  - Eliminating disparities in perinatal outcomes--lessons learned.
AB  - The disparity between blacks and whites in perinatal health ranges from a 2.3
      fold excess risk among black women for preterm delivery and infant mortality to a
      4-fold excess risk among black women for maternal mortality. To stimulate
      concerted public health action to address such racial and ethnic disparities in
      health, the national Healthy People objectives call for elimination of all health
      disparities by the year 2010. Eliminating health disparities requires a greater
      understanding of the factors that contribute to their development. This
      commentary summarizes the state of the science of reducing such disparities and
      proposes a framework for using the results of qualitative studies on the social
      context of pregnancy to understand, study, and address disparities in infant
      mortality and preterm delivery. Understanding the social context of African
      American women's lives can lead to an improved understanding of the etiology of
      preterm birth, and can help identify promising new interventions to reduce racial
      and ethnic disparities in preterm delivery.

PMID- 11573841
TI  - Closing the gap, opening the process: why study social contributors to preterm
      delivery among black women.
AB  - In the United States, the excess rates of infant mortality, VLBW, and preterm
      delivery among African American families relative to white families are known as
      "the gap." A group of researchers in the Division of Reproductive Health at the
      Centers for Disease Control and Prevention proposed that the study of causes of
      the gap in preterm delivery and the potential interventions to eliminate this
      disparity required a multidisciplinary approach to elucidate the biologic
      pathways, stressors, and social environment associated with preterm birth. They
      encouraged studies that examined the social and political impact of being an
      African American woman in the United States, racism, and the combined effects of
      gender, racism, and relative social position, as potential unmeasured etiologic
      factors that contribute to the gap. The studies conducted represent the expertise
      of anthropologists, sociologists, medical researchers, and epidemiologists who
      study both individual and social causes and then also provide a theoretical
      interpretation by those who lived the experience, (e.g., the study participants)
      rather than just the researchers' interpretation of the causes of and prevention
      strategies for the gap.

PMID- 11573842
TI  - The prevalence of socioeconomic and behavioral characteristics and their impact
      on very low birth weight in black and white infants in Georgia.
AB  - OBJECTIVES: We examined possible reasons for the disparity in the rate of very
      low birth weight (VLBW) delivery (<1500 g) in the United States between black
      women and white women. METHODS: Using data from a population-based, case-control
      study of very low birth weight infants, we compared the prevalence of
      sociodemographic and behavioral characteristics between black and white mothers
      of normal birth weight infants; the difference in these characteristics between
      case and control mothers; and, using logistic regression, calculated odds ratios
      for VLBW for black versus white infants, adjusting for these characteristics.
      RESULTS: Although black women were disadvantaged on every variable examined, they
      did not report more behavioral risk factors. Among white women, several
      traditional risk factors were associated with VLBW, while among black women, only
      marital status, cigarette smoking, and vitamin nonuse were associated with VLBW
      delivery. Controlling for the socioeconomic and behavioral factors reduced the
      odds ratio for VLBW delivery among black mothers from 3.7 to 3.3. CONCLUSIONS:
      Racial disparity in socioeconomic status may be greater than our current ability
      to adjust for it in epidemiologic studies. The fact that traditional risk factors
      were not associated with VLBW delivery in black women may be due to the very high
      prevalence of these risk factors among black women or to different or additional
      risks or stresses experienced by black women.

PMID- 11573843
TI  - Qualitative methodologies and community participation in examining reproductive
      experiences: the Harlem Birth Right Project.
AB  - OBJECTIVES: Racial disparities in health present a challenge to public health
      because of the complexity of interacting social forces. The Harlem Birth Right
      Project sought to improve understanding of these forces by using qualitative and
      community participatory methods. In this paper we 1) describe the process of
      qualitative inquiry and community involvement, 2) evaluate the impact of
      community participation, and 3) present a brief summary of the findings on social
      context as it relates to pregnancy outcomes of women in Harlem. METHODS: We
      operationalized the qualitative method by combining participant observation,
      longitudinal case studies, and focus groups. An ethnographic survey was used to
      verify and triangulate findings across methods of data collection. We involved
      the community in the design, implementation, and analysis by collaborating with
      community-based organizations, setting up a community advisory board, and the use
      of dialogue groups and community meetings. RESULTS: The use of qualitative
      methods and community partnership uncovered important aspects of the social
      context of women's lives that may not have emerged through traditional
      epidemiologic research. We found that pregnancy may serve as a catalyst to
      increase perception of the magnitude of preexisting social stressors. Several
      stressors and chronic strains associated with structural forces were identified.
      For example, the high percentage of households headed by women is seen as one
      consequence of larger structural forces. While social support networks serve as
      an important coping mechanism to buffer against the stress caused by these
      structural forces, the types of support women seek differs by social strata, and
      some strategies were identified as being substantially more effective than
      others. CONCLUSIONS: Qualitative and community participatory research can be
      successfully conducted to support public health goals and can derive important
      new information on the social context of women's lives.

PMID- 11573844
TI  - Examining the burdens of gendered racism: implications for pregnancy outcomes
      among college-educated African American women.
AB  - OBJECTIVES: As investigators increasingly identify racism as a risk factor for
      poor health outcomes (with implications for adverse birth outcomes), research
      efforts must explore individual experiences with and responses to racism. In this
      study, our aim was to determine how African American college-educated women
      experience racism that is linked to their identities and roles as African
      American women (gendered racism). METHODS: Four hundred seventy-four (474)
      African American women collaborated in an iterative research process that
      included focus groups, interviews, and the administration of a pilot stress
      instrument developed from the qualitative data. Analysis of the qualitative and
      quantitative data from the responses of a subsample of 167 college-educated women
      was conducted to determine how the women experienced racism as a stressor.
      RESULTS: The responses of the women and the results from correlational analysis
      revealed that a felt sense of obligations for protecting children from racism and
      the racism that African American women encountered in the workplace were
      significant stressors. Strong associations were found between pilot scale items
      where the women acknowledged concerns for their abilities to provide for their
      children's needs and to the women's specific experiences with racism in the
      workplace (r = 0.408, p < .001). CONCLUSIONS: We hypothesize that the stressors
      of gendered racism that precede and accompany pregnancy may be risk factors for
      adverse birth outcomes.

PMID- 11573845
TI  - Prescription drug use, diagnoses, and healthcare utilization among the elderly.
AB  - BACKGROUND: More elderly patients affected by severe and chronic diseases are
      treated in primary care. Reports on the use of prescription drugs by the general
      elderly population are scarce, and more investigations are needed to optimize
      pharmaceutical care for these patients. OBJECTIVE: To analyze prescription drug
      use, diagnoses, and healthcare utilization among noninstitutionalized elderly
      patients. DESIGN: Retrospective cohort study. SETTING AND PATIENTS: All people >
      or =65 years old (n = 4642) living in the community of Tierp, Sweden, in 1994
      were included. Prescription drug use and healthcare utilization have been
      registered for all inhabitants of the community since 1972. Information about
      filled prescriptions and diagnoses were obtained from a computerized research
      register. RESULTS: Prescription drug use was high among the elderly (78%); the
      most used pharmacologic groups were cardiovascular, nervous system, and
      gastrointestinal medications. Women used more prescription drugs than men
      (average 4.8 vs. 3.8) and had more nonfatal diagnoses. Use of five or more
      different prescription drugs during 1994 was common (39.0%), and multivariate
      analysis showed that the greatest number of primary care visits occurred with
      multiple drug use (> or =5 drugs over 1 y). CONCLUSIONS: This study shows an
      extensive multiple drug use among elderly people living at home. Whether this
      multiple drug use per se is harmful to the patients or not could not be evaluated
      in this study. Further focused investigations are needed to assess the effect of
      multiple drug use in an elderly population.

PMID- 11573846
TI  - Barriers to use of electronic adherence monitoring in an HIV clinic.
AB  - OBJECTIVE: To evaluate barriers to Medication Event Monitoring System (MEMS)
      measurement of adherence to combination antiretroviral therapy in an HIV clinic.
      DESIGN: Descriptive, cross-sectional study measured MEMS adherence to one
      antiretroviral for one month. SETTING: HIV clinic in a Veterans Affairs Medical
      Center. PARTICIPANTS: Sixty-four men on a stable antiretroviral treatment
      regimen. MAIN OUTCOME MEASURES: Decanting (removing >1 dose at a time) before and
      during monitoring over a 30-day observation period was used to determine the
      qualitative impact of MEMS on adherence. The adherence index was the proportion
      of prescribed doses not missed. RESULTS: Subjects were primarily white (73%) with
      mean CD4+ count 408 cells/mm3, log viral load 1.81 copies/mL, and duration of
      antiretroviral therapy 5.5 years. Twenty-seven (42%) had some decanting routine
      established prior to monitoring; 12(44%) of these patients used daily decanters
      and 15(56%) used weekly pillboxes. Of those who decanted prior to the study,
      10(37%) did not stop decanting during monitoring, 14 (52%) stopped decanting only
      the capped medication, and three (11%) stopped decanting all antiretrovirals.
      Other adherence strategies did not accommodate MEMS. Eight (13%) subjects said
      MEMS made adherence more difficult, six (9%) said MEMS was a reminder to adhere,
      and two (3%) mentioned both. Two subjects attributed skipped doses or time
      changes to the MEMS cap. The majority who refused to participate used pillboxes.
      CONCLUSIONS: Personal adherence strategies incompatible with MEMS are common in
      persons on complex treatment regimens. Although MEMS data on decanters
      underestimate adherence, excluding decanters erodes applicability of descriptive
      measures. MEMS use may have affected adherence behavior. Measures in conjunction
      with MEMS should include self-reported adherence and decanting assessment.

PMID- 11573847
TI  - Cerivastatin and gemfibrozil-associated rhabdomyolysis.
AB  - OBJECTIVE: To report a case of rhabdomyolysis resulting from concurrent use of
      cerivastatin and gemfibrozil. CASE SUMMARY An 82-year-old white man presented to
      the emergency department with severe muscle weakness and inability to walk
      approximately one month after starting cerivastatin. He had been taking
      gemfibrozil for several years without any known adverse effects. Both medications
      were discontinued and the patient recovered. He was discharged with a diagnosis
      of rhabdomyolysis secondary to his medications. DISCUSSION: Four previous reports
      describing rhabdomyolysis in patients on concomitant cerivastatin and gemfibrozil
      have been cited. Although monotherapy with cerivastatin is well tolerated and has
      a low frequency of adverse events, the combination with nicotinic acid (i.e.,
      niacin) or a fibric-acid derivative (i.e., gemfibrozil, fenofibrate) may result
      in severe skeletal muscle toxicity and rhabdomyolysis. CONCLUSIONS: According to
      the Naranjo scale, a probable relationship exists between the concomitant use of
      gemfibrozil and cerivastatin with the resulting development of rhabdomyolysis.
      Concurrent use of gemfibrozil and cerivastatin is therefore contraindicated.

PMID- 11573848
TI  - Olanzapine-induced rhabdomyolysis.
AB  - OBJECTIVE: To report a possible case of olanzapine-induced rhabdomyolysis with
      concomitant lithium-induced pseudo-infarction electrocardiogram changes. CASE
      SUMMARY: A 13-year-old white boy was admitted to the hospital with profound
      weakness and electrocardiogram (EGG) changes suggestive of myocardial damage
      after starting olanzapine and lithium. An adverse medication effect was not
      considered at the time of the patient's admission. The time course of onset of
      weakness was coincident with administration of olanzapine. ECG abnormalities are
      a known manifestation of lithium therapy DISCUSSION: This is a case description
      of olanzapine-induced rhabdomyolysis. Although other antipsychotic agents have
      been reported to cause rhabdomyolysis, an adverse drug reaction was not initially
      part of this patient's differential diagnosis. The patient had begun reporting
      rnyalgias six days after starting olanzapine. Fourteen days later, these symptoms
      forced him to bed rest; lithium was added for behavior misinterpreted as
      disobedience and oppositional disorder. Only when medications were considered as
      cause of the weakness and EGG changes, was the true nature of the patient's
      illness discovered. CONCLUSIONS: Olanzapine, like other neuroleptic agents, can
      cause rhabdomyolysis. Lithium can cause multiple EGG changes that can be
      misinterpreted as myocardial damage. Medication effects and adverse effects must
      always be considered in any disease complex.

PMID- 11573849
TI  - Mirtazapine for treatment of depression and comorbidities in Alzheimer disease.
AB  - BACKGROUND: Depression in patients with Alzheimer disease is a treatable cause of
      functional decline, caregiver burden, and mortality. It is often associated with
      severe weight loss, insomnia, and anxiety. These symptoms independently and
      collaboratively further worsen the prognosis of these vulnerable patients. An
      antidepressant medication with good adverse effect profile and salutary effects
      on these comorbid symptoms may be of significant therapeutic value in these
      patients. OBJECTIVE: To describe the role of mirtazapine in the treatment of
      depressed Alzheimer patients with comorbid weight loss, insomnia, and anxiety.
      CASE SUMMARY: Three patients with dementia and depression complicated by weight
      loss, insomnia, and anxiety were treated with mirtazapine at an outpatient memory
      loss clinic of a university hospital. DISCUSSION: Despite the persistence of
      memory loss, the patients experienced a prompt and sustained response to
      mirtazapine. There was a complete remission of poor appetite, weight loss, sleep
      disturbances, and anxiety. Other depression symptoms, including sad mood,
      anhedonia, and energy level, were also substantially improved. CONCLUSIONS: The
      clinical response of our patients underscores the usefulness of mirtazapine in
      the treatment of the comorbid symptoms of weight loss, insomnia, and anxiety. The
      effectiveness of mirtazapine in depressed Alzheimer patents may be a reflection
      of its enhancement of brain serotonergic and noradrenergic neurotransmission. The
      usefulness of mirtazapine in depressed Alzheimer patients merits further study in
      a large randomized, controlled, clinically comparative trial.

PMID- 11573850
TI  - Unanticipated plasma concentrations in two clozapine-treated patients.
AB  - OBJECTIVE: To report two cases of lower than anticipated clozapine plasma
      concentrations despite near maximum recommended doses of clozapine 800-900 mg/d
      in two medication-compliant schizophrenic inpatients. CASE SUMMARIES: Clozapine
      therapy was initiated in two male schizophrenic inpatients for treatment of
      psychotic symptoms refractory to other typical and atypical antipsychotics.
      Despite receiving adequate doses of clozapine for at least two months, these
      patients remained symptomatic. Therapeutic drug monitoring was used to target a
      clozapine plasma concentration of > or =250 ng/mL, the minimum value reported in
      the literature to be associated with increased clinical response. Clozapine
      plasma concentrations remained at 200 ng/mL in one patient despite dosage
      increases from 600 to 800 mg/d. In the second patient, administration of the
      maximum recommended dose resulted in concentrations between 200 and 250 ng/mL.
      Increasing the clozapine dosage to 1000 mg/d did not increase the clozapine
      plasma concentration. Evaluation of the ratio of clozapine plasma concentration
      clozapine to dose yielded lower than expected values compared with those reported
      in the literature. DISCUSSION: These two patients exhibited lower than
      anticipated clozapine plasma concentrations despite receiving high doses of
      clozapine. Several studies evaluating clozapine serum concentrations and clinical
      response have suggested threshold concentrations of > or =350 ng/mL, > or =370
      ng/mL, or > or =420 ng/mL. The only study that randomized patients to three
      concentration ranges found that patients who achieved a clozapine serum
      concentration in a medium range (mean 251 ng/mL) responded better than patients
      in a low range (mean 91 ng/mL) and similar to patients in a high range (mean 396
      ng/mL). However, attaining plasma concentrations in this range for these patients
      proved difficult. Reasons for the low concentrations are unclear and may be
      related to increased metabolic activity at several cytochrome P450 isoenzymes
      involved in the metabolism of clozapine. CONCLUSIONS: These cases illustrate
      lower than anticipated clozapine plasma concentrations despite high-dose
      clozapine therapy. Strategies to increase clozapine plasma concentrations in such
      patients might include adding a drug to partially inhibit the metabolism of
      clozapine. If those strategies are unacceptable based on risk assessment, patient
      compliance, or other reasons, clinicians may consider addition of a low-dose
      typical or other atypical antipsychotic drug to augment clozapine response.

PMID- 11573851
TI  - Eradication of severe neonatal systemic candidiasis with amphotericin B lipid
      complex.
AB  - OBJECTIVE: To report the successful use of amphotericin B lipid complex in
      treating severe systemic candidiasis in a very-low-birth-weight infant. CASE
      SUMMARY: A preterm female infant, born at 25 weeks' gestational age with a birth
      weight of 870 g, had received full supportive care in the neonatal intensive care
      unit (NICU), including mechanical ventilation, total parenteral nutrition, and
      placement of central venous catheters. At seven weeks of age, she developed
      severe disseminated candidiasis, which failed to respond to conventional
      amphotericin B and fluconazole therapy. Her progressive deterioration was
      reversed only after amphotericin B lipid complex (A-complex) was substituted for
      conventional amphotericin B. The improvement in her condition was impressive, and
      she made a full recovery without any adverse effect. DISCUSSION: With increased
      reliance on invasive technologies for life support, systemic candida infections
      have become increasingly common among premature infants in the NICU. Such
      infections are potentially fatal for the high-risk neonate. A literature review
      shows limited documentation of the use of lipid-based formulations of
      amphotericin B, especially A-complex, in preterm infants. However, the collective
      experience with these products appears to show that they are effective and cause
      fewer adverse effects than conventional amphotericin B. The infant reported here
      had shown progressive deterioration from disseminated candidiasis until
      conventional amphotericin B therapy was replaced with A-complex. Her recovery
      corresponded to the clearance of the candidemia. CONCLUSIONS: With favorable
      results and increasing experience with lipid-based formulations of amphotericin
      B, it is reasonable to consider these new formulations as therapy for candidemia
      in preterm infants who are at a high risk of nephrotoxicity or who have failed
      conventional therapy.

PMID- 11573852
TI  - Amphotericin B-induced seizures in a patient with AIDS.
AB  - OBJECTIVE: To report a case of multiple episodes of seizure activity in an AIDS
      patent following amphotericin B infusion. CASE SUMMARY: A 46-year-old African
      American man experienced recurrent grand mal seizures during intravenous infusion
      of amphotericin B, then petit mal seizures as the infusion was stopped and the
      drug concentrations decreased with time. The patients concurrent medications
      included didanosine, hydroxyzine, promethazine, hydrocortisone, and
      prochlorperazine. Despite administration of phenytoin and lorazepam, the seizures
      persisted and occurred only during amphotercin B administration. DISCUSSION: AIDS
      and cryptococcal meningitis, both of which the patient had, can potentially cause
      seizures. The patient had a history of alcohol abuse; alcohol intake as well as
      withdrawal can also cause seizures. Didanosine also has a potential for inducing
      seizures. However, these other potential causes of seizure were ruled out. The
      time course of events suggested that amphotericin B was the cause of the seizures
      in this AIDS patient. CONCLUSIONS: Amphotericin B seems to be the probable cause
      of the seizures. To date, only three cases of seizures associated with
      amphotericin B have been reported in the literature, but healthcare providers
      should be aware of the potential for this rare adverse effect.

PMID- 11573853
TI  - Transient hypoparathyroidism due to amphotericin B-induced hypomagnesemia in a
      patient with beta-thalassemia.
AB  - OBJECTIVE: To report a case of transient hypoparathyroidism that developed in a
      beta-thalassemic patient due to amphotericin B-induced hypomagnesemia. CASE
      SIJMMARY: A 21-year-old man with beta-thalassemia was treated with amphotericin B
      for Candida albicans intravenous line sepsis. After five days of treatment
      (cumulative dose 160 mg), he developed hypomagnesemia, which caused
      hypoparathyroidism and hypocalcemia; all three abnormalities resolved after the
      drug was withdrawn. DISCUSSION: Patients with beta-thalassemia may develop
      endocrinologic abnormalities due to excessive iron deposition. Some may have
      subclinical hypoparathyroidism that clinically emerges after even a mild
      homeostasis disturbance. Amphotericin B is associated with variable adverse
      effects including renal tubular insult, which may induce hypomagnesemia following
      relatively short treatment. The resolution of hypomagnesemia, hypocalcemia, and
      hypoparathyroidism in our patient after discontinuation of amphotericin B
      treatment suggests that the endocrine dysfunction was due to a drug-related
      adverse effect and not to parathyroid dysfunction caused by iron deposition.
      CONCLUSIONS: This case demonstrates a known but rarely reported adverse effect of
      amphotericin B, namely hypomagnesemia, that may occur even at a low cumulative
      dose. It also emphasizes that patients with an underlying disease, such as
      thalassemia, may be more susceptible to hypoparathyroidism and hypocalcemia
      during treatment with amphotericin B.

PMID- 11573854
TI  - Delirium following a switch from cimetidine to famotidine.
AB  - OBJECTIVE: To describe a patient who developed delirium when switched from
      cimetidine to famotidine. CASE SUMMARY: An 84-year-old Taiwanese woman was
      hospitalized for tarry stools. Her past medical history revealed only a decrease
      in renal function. She tolerated both oral and intravenous cimetidine therapy
      with a daily dose of 400-900 mg intermittently for 20 years. On hospital days 1
      3, cimetidine 300 mg was injected intravenously every eight hours without
      difficulty. Considering the possible existence of a cimetidine-resistant bleeding
      ulcer, famotidine 20 mg was given twice daily orally on hospital days 4-7 and
      then injected intravenously. Six days after being switched from cimetidine to
      famotidine, the woman's mental status deteriorated. A series of clinical tests
      revealed no apparent causative factors. Famotidine was then suspected as a
      probable cause of her delirium. Discontinuation of the drug resulted in rapid
      resolution of the patient's delirious status. DICUSSION: Famotidine crosses the
      blood-brain barrier less easily than cimetidine and was taken for a much shorter
      period in this patient. Thus, we propose that the occurrence of delirium in this
      patient was associated with famotidine, but not cimetidine, and was idiosyncratic
      rather than dose related. Furthermore, this case involved an elderly patient with
      compromised renal function who developed delirium in response to intravenous, but
      not oral, administration of famotidine. These factors seem to increase the risk
      for, famotidine-induced delirium. CONCLUSIONS: Clinicians should be aware of the
      possible occurrence of delirium following a switch from one histamine2-receptor
      antagonist to another. In rare instances, patients switched to famotidine from
      cimetidine may experience delirium, particularly elderly patients with poor renal
      function who receive intravenous famotidine.

PMID- 11573855
TI  - Nimesulide-induced acute hepatitis.
AB  - OBJECTIVE: To report the occurrence of nimesulide-induced acute hepatitis
      confirmed by biopsy and an in vitro lymphocyte toxicity assay. CASE SUMMARY: A 54
      year-old Arabic woman treated with nimesulide for chronic low back pain was
      admitted to the hospital with acute hepatitis confirmed by biopsy. Her liver
      function test results returned to normal within one month after nimesulide
      discontinuation. An in vitro lymphocyte toxicity assay confirmed that the liver
      injury was due to nimesulide exposure. DISCUSSION: A case of acute hepatitis
      secondary to nimesulide, confirmed by biopsy and a laboratory in vitro assay, is
      described. Although the occurrence of clinically significant liver damage due to
      nonsteroidal antiinflammatory drugs (NSAIDs) is low, the enormous consumption of
      these drugs has made them an important cause of liver damage. Nimesulide, a
      relatively new NSAID commonly used in Europe, with a relative selectivity to
      cyclooxygenase type 2, can cause a wide range of liver injuries, from mild
      abnormal liver function to severe liver injuries. These effects are usually
      reversible on discontinuation of the drug, but occasionally can progress to fatal
      hepatic failure. CONCLUSIONS: Drug-induced acute hepatitis is a well-recognized
      adverse effect of many drugs, including nimesuilde. Identification of a drug as a
      cause for this life-threatening disease is important because the discontinuation
      of it may be life saving. This article confirms the occurrence of nimesulide
      induced hepatitis. It also highlights the importance of monitoring liver function
      test results after initiating therapy with such a drug.

PMID- 11573856
TI  - Acute hepatitis induced by cyproterone acetate.
AB  - OBJECTIVE: To report a case of acute hepatitis resulting from the use of
      cyproterone acetate, an adjuvant treatment for prostate cancer. CASE SUMMARY: An
      87 year-old white man, admitted to surgery for prostate cancer, received
      cyproterone acetate 300 mg/d orally and developed acute hepatitis, which
      initially was diagnosed clinically. A liver biopsy showed changes suggestive of
      acute cholestatic hepatitis. Cyprotorone was stopped immediately, and the patient
      was subsequently treated with corticosteroids. He then improved rapidly.
      DISCUSSION: Cyproterone acetate is thought to be well tolerated, but some authors
      have reported severe hepatic reactions, in particular acute hepatitis, fatal
      fulminant hepatic failure, and hepatocellular carcinoma. The above-mentioned
      hepatotoxicity represents an idiosyncratic drug reaction, probably due to the
      hepatomitogen action of cyproterone, causing an increase of hepatocytes
      expressing placental glutathione S-transferase, which are considered
      preneoplastic elements. CONCLUSION: This case suggests the possibility of
      hepatotoxicity from cyproterone.

PMID- 11573857
TI  - Oral bexarotene in the treatment of cutaneous T-cell lymphoma.
AB  - OBJECTIVE: To review the preclinical and clinical information related to oral
      bexarotene approved by the Food and Drug Administration for the treatment of
      cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are
      refractory to at least one prior systemic therapy. DATA SOURCES: Literature
      accessed through MEDLINE (from 1990 to July 2000) and provided by the
      manufacturer. Key search terms included bexarotene, Targretin, LGD1069, and
      cutaneous T-cell lymphoma. DATA SYNTHESIS: The management of CTCL remains
      controversial due to its rarity in the US and its heterogeneity. An evaluation
      focusing on the pharmacology of bexarotene and its role in the management of the
      different stages of CTCL was conducted. CONCLUSIONS: Bexarotene has demonstrated
      activity in the treatment of CTCL. The oral route of administration and the
      adverse effect profile of bexarotene appear to make this drug a favorable option
      for the treatment of CTCL. Compared with other systemic therapies. Phase III
      randomized studies are needed to determine the clinical benefits of bexarotene as
      monotherapy or combination therapy in the treatment of CTCL.

PMID- 11573858
TI  - Mediators of chronic heart failure: how drugs work.
AB  - OBJECTIVE: To critically review the pathophysiology of chronic heart failure at
      the neurohormonal level, and discuss the effect of present and future therapeutic
      options on these neurohormones. DATA SOURCES: A MEDLINE search (1986-November
      2000) was used to identify important primary literature and reviews. Additional
      references were obtained from these articles. DATA SYNTHESIS: Chronic heart
      failure is a common, progressive disorder with high morbidity and mortality.
      Progression is due in large part to several redundant neurohormonal responses.
      The neurohormones include angiotensin II, norepinephrine, aldosterone, endothelin
      1, arginine vasopressin, and tumor necrosis factor. These responses are initially
      adaptive, but become maladaptive in the long term, impairing the function of the
      heart, vasculature, and kidneys. Counter-regulatory hormones, such as bradykinin
      and natriuretic peptides, are insufficient to offset the adverse effects of the
      other neurohormones. Most drugs used to treat chronic heart failure, such as
      angiotensin-converting enzyme inhibitors, beta-adrenergic antagonists, and
      spironolactone, achieve their benefits through altering the neurohormonal
      pathways. New agents that affect more or different neurohormones may soon be
      available. CONCLUSIONS: Multiple agents are required for treatment of chronic
      heart failure, as no single agent can counteract all of the various adverse
      pathways. The appropriate prescription and use of such inherently complex
      regimens require significant physician and patient education.

PMID- 11573859
TI  - Antifibrinolytic agents and desmopressin as hemostatic agents in cardiac surgery.
AB  - OBJECTIVE: To review the use of systemic hemostatic medications for reducing
      bleeding and transfusion requirements with cardiac surgery. DATA SOURCES:
      Articles were obtained through computerized searches involving MEDLINE (from 1966
      to September 2000). Additionally, several textbooks containing information on the
      diagnosis and management of bleeding associated with cardiac surgery were
      reviewed. The bibliographies of retrieved publications and textbooks were
      reviewed for additional references. STUDY SELECTION: Due to the large number of
      randomized investigations involving systemic hemostatic medications for reducing
      bleeding associated with cardiac surgery, the article selection process focused
      on recent randomized controlled trials, metaanalyses and pharmacoeconomic
      evaluations. DATA EXTRACTION: The primary outcomes extracted from the literature
      were blood loss and associated transfusion requirements, although other outcome
      measures such as mortality were extracted when available. DATA SYNTHESIS:
      Although the majority of investigations for reducing cardiac bleeding and
      transfusion requirements have involved aprotinin, evidence from recent meta
      analyses and randomized trials indicates that the synthetic antifibrinolytic
      agents, aminocaproic acid and tranexamic acid, have similar clinical efficacy.
      Additionally, aminocaproic acid (and to a lesser extent tranexamic acid) is much
      less costly. More comparative information of hemostatic agents is needed retative
      to other outcomes (eg., reoperation rates, myocardial infarction, stroke). There
      is insufficient evidence to recommend the use of desmopressin for reducing
      bleeding and transfusion requirements in cardiac surgery, although certain
      subsets of patients may benefit from its use. CONCLUSIONS: Of the medications
      that have been used to reduce bleeding and transfusion requirements with cardiac
      surgery, the antifibrinolytic agents have the best evidence supporting their use.
      Aminocaproic acid is the least costly therapy based on medication costs and
      transfusion requirements.

PMID- 11573860
TI  - Is more than one quinolone needed in clinical practice?
AB  - OBJECTIVE: To review clinical information on fluoroquinolone antimicrobials to
      distinguish between these agents and help define their place in clinical
      practice. DATA SOURCES: Primary and review articles on fluoroquinolones available
      commercially in the US as of August 2000 were identified through MEDLINE (from
      1993-August 2000) and secondary sources. STUDY SELECTION AND DATA EXTRACTION: All
      pertinent, published, clinical trials for levofloxacin, moxifloxacin, and
      gatifloxacin were included. Minimal data were included for quinolones with
      restricted or limited uses, including trovafloxacin, sparfloxacin, enoxacin, and
      lomefloxacin. Due to the quantity of data on ciprofloxacin, only more recent or
      pivotal trials or articles summarizing data on specific infections were included.
      Relevant information was included if it was believed to assist in differentiating
      between the fluoroquinolones for infections for which these agents would most
      commonly be considered. DATA SYNTHESIS: Fluoroquinolones are a potent class of
      intravenous and oral broad-spectrum antimicrobial agents used for treating a wide
      range of community-acquired and nosocomial infections. More than 10 quinolones
      have been approved for use; although some of these have been withdrawn from the
      market, numerous others are under investigation. It has become increasingly
      important to be able to differentiate between these agents. CONCLUSIONS:
      Differences in safety, antimicrobial spectrum of activity, and resistance
      development support the selective use of various fluoroquinolones in differing
      clinical situations.

PMID- 11573861
TI  - Rhabdomyolysis and HMG-CoA reductase inhibitors.
AB  - OBJECTIVE: To review rhabdomyolysis and discuss the role of hydroxymethylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors (statins) and their interactions with
      other agents in precipitating this condition, and to present case reports of
      statin-induced rhabdomyolysis. DATA SOURCE: Relevant clinical literature was
      accessed using MEDLINE (January 1985-October 2000). The following search terms
      were used: rhabdomyolysis, adverse events, drug interactions, statins, and HMG
      CoA reductase inhibitors. DISCUSSION: Rhabdomyolysis occurs when extensive muscle
      damage results in the release of cellular contents into systemic circulation.
      Major complications include acute renal failure, cardiac abnormalities, and
      compartment syndrome. Treatment of rhabdomyolysis is supportive, with the primary
      aim of preventing renal and cardiac complications. Statin monotherapy or
      combination therapy may result in myopathy, which rarely progresses to
      rhabdomyolysis. The mechanism for drug interactions with the statins involves
      their property of lipid or water solubility. This characteristic determines the
      degree of hepatoenteric or renal metabolism of the statins. All statins except
      pravastatin undergo metabolism via the cytochrome P450 enzyme system. Other
      pharmacologic agents that are also metabolized via this pathway may interact with
      the statins and cause rhabdomyolysis. The risk of statin-induced rhabdomyolysis
      is increased significantly when statins are used concomitantly with such drugs as
      fibrates, cyclosporine, macrolide antibiotics, and azole antifungals.
      CONCLUSIONS: Rhabdomyolysis is a rare but clinically important adverse event of
      statin monotherapy or combination therapy. Thorough understanding of this
      condition may help prevent or minimize adverse health outcomes in patents
      receiving statin therapy.

PMID- 11573862
TI  - Cilostazol for prevention of thrombosis and restenosis after intracoronary
      stenting.
AB  - OBJECTIVE: To evaluate the potential use of cilostazol in intracoronary stenting.
      DATA SOURCES: Clinical literature was accessed through MEDLINE (1966-March 2001).
      Key search terms included cilostazol, intracoronary stenting, and coronary
      angioplasty. Abstracts of clinical trials presented at major cardiology
      professional association meetings were also reviewed. DATA SYNTHESIS:
      Intracoronary stent placement represents the fastest growing medical device
      implant. Complications of stent implantation include acute and subacute vessel
      closure, as well as late restenosis. Currently, antiplatelet agents are used for
      preventive therapy. Cilostazol is a vasodilating antiplatelet agent that
      reversibly inhibits platelet aggregation induced by many factors. In seven
      randomized trials comparing cilostazol with either aspirin or ticlopidine,
      cilostazol was found to be superior to aspirin and equivalent to ticlopidine in
      decreasing both cardiac events and rates of restenosis. In addition, cilostazol
      was found to be well tolerated, with no reports of adverse hematologic events.
      CONCLUSIONS: Although further comparative trials are required, cilostazol appears
      to be a safe and effective alternative to clopidogrel and glycoprotein IIb/IIIa
      receptor antagonists following intracoronary stent implantation.

PMID- 11573863
TI  - Prophylaxis for paclitaxel hypersensitivity reactions.
AB  - OBJECTIVE: To evaluate clinical literature supporting the prophylactic use of
      single-dose intravenous dexamethasone to prevent hypersensitivity reactions
      (HSRs) to paclitaxel infusion. DATA SOURCES: Clinical literature accessed through
      MEDLINE (from 1986 to 2000). DATA SYNTHESIS: Prophylaxis for paclitaxel-related
      HSRs generally includes repeated dexamethasone doses beginning 12 hours before
      paclitaxel, and administration of diphenhydramine plus a histamine2-receptor
      antagonist 30 minutes before infusion of paclitaxel. Singe-dose intravenous
      dexamethasone administered with ancillary medications 30 minutes before infusion
      of paclitaxel has been used to prevent regimen-related HSRs. CONCLUSIONS: Single
      dose intravenous dexamethasone can be used in combination with appropriate
      ancillary medications to prevent paclitaxel-related HSRs.

PMID- 11573864
TI  - Effects of soy phytoestrogens genistein and daidzein on breast cancer growth.
AB  - OBJECTIVE: To determine whether genistein and daidzein, the major phytoestrogens
      in soy, can stimulate breast cancer growth. DATA SYNTHESIS: Systematic search
      through primary English-language literature on MEDLINE (1966-January 2001),
      EMBASE (1982-January 2001) and Current Contents (1998-January 2001). DATA
      SOURCES: Genistein and daidzein at low concentrations were found to stimulate
      breast tumor growth in in vitro and in vivo animal studies, and antagonize the
      antitumor effect of tamoxifen in vitro. At high concentrations, genistein
      inhibited tumor growth and enhanced the effect of tamoxifen in vitro.
      CONCLUSIONS: Genistein and daidzein may stimulate existing breast tumor growth
      and antagonize the effects of tamoxifen. Women with current or past breast cancer
      should be aware of the risks of potential tumor growth when taking soy products.

PMID- 11573865
TI  - Infrastructure of pharmaceutical research and development in Japan.
AB  - OBJECTIVE: To examine the roles of different types of hospitals in implementation
      of multicenter Phase II/III trials in Japan, specifically focusing on two
      dichotomies: public versus private, and academic versus nonacademic. Possible
      explanation was sought as to why a hospital of one category was more likely to
      participate in specific types of trials in the Japanese medical environment.
      METHODS: A database containing attributes of published clinical trials (n = 217)
      was established from four journals featuring reports of clinical trial results.
      The preferences of public and academic hospitals for specific types of trials
      were estimated by applying a linear regression model. The trial compositions of
      these institutions were also estimated, taking the actual prevalence of trials in
      1995 into consideration. RESULTS: Public sector hospitals, which were established
      for particular policy purposes in the national healthcare system, were more
      likely to accept trials in some fields (e.g., cardiovascular diseases,
      anesthesiology, antineoplastics, pediatrics) and of some kinds (e.g., Phase II
      rather than Phase III trials, trials supervised by the principal investigator in
      the public sector). Academic hospitals also showed preferences for some types of
      trials (e.g., cardiovascular diseases, dermatology; Phase II rather than Phase
      III trials). The analysis focusing on public hospitals suggested that policy
      purposes were achieved at least in some fields such as antineoplastics and
      anesthesiology. CONCLUSIONS: Japanese clinical trials were unevenly distributed
      between public and private sectors, and also between academic and nonacademic
      sectors. These data provide fundamental information about the clinical research
      environment for future pharmaceutical research and development strategies and
      policies.

PMID- 11573866
TI  - Treatment of attention deficit hyperactivity disorder in children.
AB  - These are controversial times for those who care for children with attention
      deficit hyperactivity disorder (ADHD). Class action law suits have been filed in
      federal courts in California and New Jersey accusing a manufacturer of
      methylphenidate and the American Psychiatric Association of conspiring to expand
      the use of this drug. These suits have recently been dismissed. This is just the
      latest chapter in the long-running debate over the existence, diagnosis, and
      treatment of ADHD. Controversies relating to ADHD continue to polarize
      physicians, educators, caregivers, and parents of these children. There are those
      who believe that ADHD does not exist as a true disorder. At the other end of the
      spectrum are those who are too quick to make the diagnosis without an adequate
      patient workup. Parents can unfortunately get caught in the middle of this debate
      when making treatment decisions for their children.

PMID- 11573867
TI  - Condoms and sexually transmitted diseases.
AB  - Many of our patients and colleagues will be surprised and disturbed by the latest
      revelation from the National Institutes of Health (NIH) and the Centers for
      Disease Control and Prevention (CDC). For more than a decade, the NIH and CDC
      have been promoting "safe sex," a message apparently based solely on the hope
      that condoms are effective in prevention of sexually transmitted diseases (STDs).
      This hope was discredited in mid-July when the NIH released the "Scientific
      Evidence on Condom Effectiveness for STD Prevention," commissioned in June 2000
      by then-House member, Dr. Tom Coburn (R-OK). The report disclosed that the body
      of medical research shows no evidence that condoms protect against most STDs. I
      refer to the NIH and CDC's "hope" because their recommendations have not been
      based on good science, but rather on theoretical models, possibly unduly
      influenced by a strong bias that condoms would prove to be effective.

PMID- 11573868
TI  - Are condoms effective in reducing the risk of sexually transmitted disease?
AB  - A panel of more than two dozen experts reviewed the scientific evidence on condom
      effectiveness for sexually transmitted disease (STD) prevention, and a final
      report was released July 20, 2001, by the Department of Health and Human
      Services. This panel was cosponsored and convened for a two-day workshop by four
      government agencies (Agency for International Development, Food and Drug
      Administration, Centers for Disease Control and Prevention [CDC], and the
      National Institutes of Health [NIH]).

PMID- 11573869
TI  - Weight loss with topiramate.

PMID- 11573870
TI  - History of drug-induced hepatitis and risk of amoxicillin/clavulanate-induced
      hepatotoxicity.

PMID- 11573871
TI  - Comment: comparison of FDA reports of patient deaths associated with sildenafil
      and injectable alprostadil.

PMID- 11573872
TI  - Comment: serotonin syndrome and 5-HT2A antagonism.

PMID- 11573873
TI  - Lack of tacrolimus-induced cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) has been reported in pediatric
      transplant patients receiving tacrolimus. It is unclear whether tacrolimus is
      associated with HCM in adult transplant recipients. OBJECTIVE: To determine the
      prevalence of HCM in noncardlac adult transplant patients receiving tacrolimus.
      METHODS: A retrospective analysis of nonheart transplant recipients who received
      tacrolimus at our institution from January 1982 to April 1996 was conducted.
      Patients with left-ventricular hypertrophy (LVH) defined as a posterior or septal
      wall thickness > or = 1.3 cm by echocardiography (ECHO) were independently
      evaluated. RESULTS: There were 3609 patients who met entry criteria including
      2257 liver, 1333 kidney, and 19 other organ transplants. Of the 502 patients who
      had undergone ECHOs after transplantation, 171 had LVH. The etiology of LVH was
      categorized as valvular disease (36%), hypertensive disease (29%), ischemic heart
      disease (17%), or multifactonal (15%). There were six patients in whom, after
      detailed chart review, no underlying cause of LVH was evident. Five of these
      patients had HCM, representing an overall prevalence of 0.1% in the entire group
      of tacrolimus-treated patients, and 1% in patients referred for ECHO.
      CONCLUSIONS: The prevalence of HCM in our tacrolimus-treated adult transplant
      population is similar to that reported in general population studies. These data
      suggest that tacrolimus is not a risk factor for HCM in adult transplant
      recipients.

PMID- 11573874
TI  - Newness of drugs and use of HMO services by asthma patients.
AB  - OBJECTIVE: To define newness of drug technology and show associations between two
      measures of newness and health service utilization. METHODS: Healthcare use and
      changes in severity at each office visit were assessed for 1309 asthma patients
      from six health maintenance organizations (HMOs) during 1992. The age of each
      drug product, derived by subtracting its Food and Drug Administration (FDA)
      approval date from January 1, 1992, was used to construct two newness measures:
      the average age of all asthma drugs and, separately, all non-asthma drugs a
      patient used during the year and the percentages of a patient's asthma drugs from
      each of four time intervals of asthma drug breakthroughs. Service utilization
      variables included all primary care provider (PCP) visits, total prescription
      costs, emergency department (ED) visits, and hospitalizations. RESULTS: Using
      either measure of drug newness, multivariate analyses showed an association
      between greater use of newer asthma drugs and lower overall drug costs and fewer
      PCP visits. A trend was found between greater use of newer asthma drugs and fewer
      hospitalizations and ED visits. Newer non-asthma medications were associated with
      fewer ED visits. CONCLUSIONS: After controlling for patient and site variables,
      greater use of newer asthma drugs was associated with significantly lower drug
      costs and fewer PCP visits; associations with hospitalization rates and ED
      visits, although lower, were not significant.

PMID- 11573875
TI  - Compliance from self-reported versus pharmacy claims data with metered-dose
      inhalers.
AB  - OBJECTIVE: To determine how well self-reported compliance with metered-dose
      inhalers (MDIs) agrees with compliance determined from pharmacy claims data.
      Additional analyses were conducted to establish phychmetric properties of the
      questionnaire. METHODS: A cross-sectional survey was performed of all adult
      enrollees with asthma of a managed care organization. The overall return rate was
      63.4% (696/1098). Patents with persistent asthma and at least one prescription
      claim for a controller MDI during the four months preceding the survey were
      included. Pharmacy claims data were used to calculate a compliance ratio. Self
      reported compliance was based on a four-item questionnaire. The primary end
      points were the percent-agreement and the overall correlation between the two
      measures. The questionnaire's internal reliability and construct validity were
      assessed using Cronbach's alpha and Pearson's correlations, respectively. Mean
      item response scores for compliant patients were compared with scores of
      noncompliant patients using the Student's t-test. RESULTS: One hundred
      questionnaire respondents met the study criteria. The mean +/- SD compliance
      ratio was 0.52+/-0.27, the mean +/- SD self-reported compliance score was 4.07+/
      1.0. The overall percent agreement and correlation between self-reported
      compliance score and the compliance ratio were 75.5% and r = 0.348 (p = 0.01),
      respectively. The percent agreement was highest (85%) when noncompliant patients
      (by compliance ratio <0.8) reported being noncompliant (questionnaire score <5).
      Cronbach's alpha was 0.86. CONCLUSIONS: This study demonstrated a moderate
      correlation between self-reported asthma compliance and the compliance ratio
      determined using claims data. The questionnaire may be useful as a screening tool
      to detect noncompliant behavior in populations or individual patients with
      asthma.

PMID- 11573876
TI  - Functional testing of elderly subjects after lower limb amputation.
AB  - The aim of the present study was to find out if it is possible to use the same
      functional tests for elderly subjects after lower limb amputation who live
      independently at their homes as for healthy ones. Will these tests discriminate
      among different problems in subjects with different levels and different causes
      of amputation and will they discriminate between active and sedentary subjects?
      The study examined 83 volunteers who lived independently at their homes (55
      healthy sedentary, 17 after trans-tibial amputation, 11 after trans-femoral
      amputation). All subjects were aged 60 or older. All subjects after lower limb
      amputation were found to have significantly worse results in almost all tests in
      comparison with the healthy sedentary men. The subjects after transfemoral
      amputation needed significantly more time at the "up and go" test, walked a
      shorter distance in 9 minutes. and performed fewer stand-ups from a chair and
      fewer steps in two minutes than the subjects after trans-tibial amputation. The
      active subjects after lower limb amputation had better balance, were quicker at
      the "up and go" test and walked longer in a minute than the sedentary subjects
      after lower limb amputation. It can be concluded that this test battery can also
      be used to test subjects after lower limb amputation because it discriminates
      among different severity of problems in subjects with different level and cause
      of amputation as well as between active and sedentary ones.

PMID- 11573877
TI  - Landmine amputees referred to the Royal Medical Services-Jordan.
AB  - OBJECTIVE: To assess the epidemiology of landmine amputees at the Royal Medical
      Services (RMS) in Jordan. METHODS: This is a retrospective study of patients with
      amputation due to landmine explosions seen in the prosthetics-orthotics clinic at
      the RMS in Jordan between January 1988 and January 2000. The records of all
      patients injured through landmine explosions were available for study. RESULTS:
      During the 12-year study period, 226 patients with 241 amputations were seen in
      the clinic. Of these 212 (94%) were male, and 14 (6%) were female. Military
      personnel comprised 68.6% of the total. The majority of amputations involved the
      lower limbs, and the most frequent level was trans-tibial. Most of the patients
      were injured in the 1970s and 1990s. The majority of the patients were young, and
      10% of the patients were children. CONCLUSION: The occurrence of amputations from
      landmine injuries in Jordan is considerable, and places a significant burden on
      the health care system.

PMID- 11573878
TI  - Silicone roll-on suspension for upper limb prostheses: users' views.
AB  - OBJECTIVE: To determine the perceived benefit, pattern of use and problems of the
      ICEROSS socket for upper limb prostheses. DESIGN: Structured questionnaire sent
      to patients provided with ICEROSS systems. SETTING: NHS artificial limb clinic.
      SUBJECTS: All patients (20) who have used an upper limb prosthesis with an
      ICEROSS inner socket between 1995-1999. MAIN OUTCOME MEASURES: Purpose-designed
      questionnaire. RESULTS: Replies were obtained from 18 patients. Eight (8)
      amputees continue to use their ICEROSS limb regularly (44%) after a mean of 32
      months. Ten (10) amputees stopped using the ICEROSS system. Six (6) developed
      persistent skin problems, 2 switched to myoelectric prostheses, 1 was unable to
      put the ICEROSS on independently and 1 amputee stopped using all kinds of
      prostheses because he did not find them useful. Fourteen (14) amputees complained
      of phantom pain, 4 of whom reported worsening of the pain with ICEROSS sockets.
      CONCLUSION: The ICEROSS socket provides good suspension for upper limb
      prostheses, but its use is limited by skin problems and incompatibility with
      myoelectric contacts.

PMID- 11573879
TI  - Clinical results of an investigation of paediatric upper limb myoelectric
      prosthesis fitting at the Quebec Rehabilitation Institute.
AB  - This study was designed to investigate the satisfaction level of young users of
      myoelectric prostheses who received an upper limb myoelectric prosthesis, to
      assess their dropout rate and to identify which factors influence the use or non
      use of the upper limb myoelectric prosthesis in the eastern part of Quebec
      (Canada). The users were fitted between 1990 and 1999 at the Quebec
      Rehabilitation Institute, a major rehabilitation centre located in the province
      of Quebec. This rehabilitation centre provides cutting-edge expertise not only
      for the eastern part of Quebec, but also across the entire province, because it
      is one of only two highly specialised centres serving all of Quebec. A literature
      review was completed to compile the results obtained in other rehabilitation
      centres and to identify factors influencing the use or non-use of paediatric
      upper limb myoelectric prostheses. The Quebec User Evaluation of Satisfaction
      with Assistive Technology (QUEST) was used in order to assess the degree to which
      the children were satisfied with their prostheses. Eighteen (18) children were
      fitted and trained to use an upper limb myoelectric prosthesis. A total of 10
      children and parents agreed to participate. Some 80% of participants said that
      they were satisfied with their prostheses. A dropout rate of 53% for the overall
      group (participants and non-participants) seems high compared with that of other
      studies. Recommendations linked to factors identified in the literature are made.
      The authors conclude that a multidisciplinary team and structured training and
      follow-up can improve the clinical results pertaining to all the factors proposed
      in the literature.

PMID- 11573880
TI  - Evaluation of a screening and prevention programme for diabetic foot
      complications.
AB  - Foot complications in diabetes can be decreased by preventive measures. The
      authors evaluated the current diabetic foot screening and prevention programme of
      the diabetes outpatient clinic of their university hospital, by assessing the
      presence of risk factors for the development of foot disorders and the preventive
      measures taken. Fifty (50) diabetic patients not known to have foot complications
      were selected at random. Risk factors and preventive measures were inventarised
      with the Coleman risk-categorization system and the Preventive Measures Scale,
      respectively. Sixty per cent (60%) of the patients were at risk of developing
      diabetic foot complications. The preventive measures were low in these patients.
      Patient knowledge was insufficient and behaviour even worse. Basal preventive
      shoe adaptations were absent in most patients at risk. No relation between risk
      category and the preventative status was found. Cross-sectional examination at a
      university outpatient clinic showed serious risk profiles for foot complications,
      which were not balanced by the application of generally accepted preventive
      measures. At the outpatient clinic, screening should be optimised.

PMID- 11573881
TI  - Orthotic management of the lower limb in children with hereditary motor sensory
      neuropathy (HMSN).
AB  - The lower limbs of 55 paediatric patients, with the diagnosis of hereditary motor
      sensory neuropathy (HMSN) referred to the Orthotics and Biomechanics Department
      of Hacettepe University, were assessed for appropriate orthotic intervention.
      Since in the natural history of HMSN symptoms and complaints are variable there
      is a wide range of interventions possible. The biomechanics of deforming forces
      and the consequential incidence of deformities in these 55 children, its orthotic
      implications and the efficacy of orthotic applications are discussed in detail.

PMID- 11573882
TI  - Results of supracondylar osseous shortening in knee disarticulation.
AB  - A twenty-eight-year-old patient who had a knee disarticulation and used a
      prosthesis that could bear weight through the stump end is presented. He had
      cosmetic and soft tissue problems in the stump end. To solve these problems, a 7
      cm supracondylar shortening osteotomy was performed. The functional and cosmetic
      results that were obtained from the prosthesis for trans-femoral amputations but
      which can bear weight through the stump end, fitted 1.5 months after the surgical
      operation, were evaluated as very good at the end of the 26 months follow-up
      period.

PMID- 11573883
TI  - Failure diagnosis of a type of hydraulic knee joint controller.
AB  - The development of the hydraulic artificial knee joint controller has
      significantly improved the quality of life for many amputees. Even though the
      controller unit is very reliable, gradual deterioration inevitably takes place
      because the unit consists of many moving parts and is subjected to repetitive
      loads. This paper describes a simple method to test the reliability of hydraulic
      artificial knee joint controllers. A life cycle testing machine for artificial
      knee controllers was designed part of this programme. This study included life
      cycle testing of 5 knee controllers. Performance measurements representing the
      different degrees of deterioration were recorded and correlated against the
      actual deterioration found during refurbishment of the units. The results can be
      used (with care), together with simple tests, to judge performance of a given
      unit.

PMID- 11573884
TI  - Inclusion of battery level meter in a standard myoelectric prosthesis.

PMID- 11573885
TI  - Tetraplegic ambulation with the ORLAU swivel walker: a case report.
AB  - The ORLAU Swivel Walker which had previously been used by children with spina
      bifida. has been modified so that it is now being successfully used by spinal
      cord paralysed patients. This is a case study of a C7 traumatic tetraplegic
      patient who has used the ORLAU swivel walker for 5 years.

PMID- 11573886
TI  - The Knud Jansen Lecture. A personal view of prosthetics and orthotics.

PMID- 11573887
TI  - A portable system for the measurement of the temporal parameters of gait.
AB  - An easy-to-use, low cost, portable system is presented. It consists of a
      transmitter, four electrical sensors, a receiver and a PC with the appropriate
      software. The system can assess footfall timing, that is the single limb support,
      double limb support, single step duration values, and the gait cycle duration.
      This system has been tested for its accuracy with known signals. Then,
      measurements on a group of twenty (20) healthy adults were performed, with
      statistically insignificant (p>0.2) results to those reported in the literature.
      The above prove the system's validity for temporal gait analysis.

PMID- 11573888
TI  - The future may not be so dark.

PMID- 11573889
TI  - False diagnosis of tuberculosis.

PMID- 11573890
TI  - Sarcoidosis.
AB  - Much has been learned over the last decade about the genetic predisposition to
      different patterns of sarcoidosis and its pathogenesis. These major advances have
      been possible through the very rapid evolution of newer molecular technology. The
      last two years have also seen the publication of an international statement on
      sarcoidosis that defines very clearly the presentation, clinical features,
      diagnosis and treatment of sarcoidosis and also clearly identifies areas where we
      need to know more. This review aims to highlight key issues that have emerged
      over the last five years. Specific focus is given to genetic predisposition and
      trigger factors-molecular epidemiology. The more novel approaches that have been
      taken to attempt to treat this disease more effectively are also addressed.

PMID- 11573891
TI  - Variation in vulnerability to tuberculosis in America today: random, or legacies
      of different ancestral epidemics?
AB  - OBJECTIVE: To test the hypothesis that vulnerability to infection by
      Mycobacterium tuberculosis is the norm for mankind but innate resistance to the
      infection is common in the USA today as a legacy of TB epidemics survived by
      one's ancestors. MEASUREMENTS: A reaction of 10 mm or more to a tuberculin skin
      test (TST) was used to determine the prevalence of infection following community
      outbreaks of the disease. For further information, a survey was conducted of
      prevalence of tuberculin reactivity among health-care workers with frequent
      exposures to tuberculosis patients during bronchoscopy and sputum collection.
      RESULTS: Sixty per cent of African Americans exposed in 26 community outbreaks
      were TST positive compared to only 40% of whites following comparable exposures.
      Similarly only 56 (41.2%) of 136 heavily exposed white health-care workers were
      TST positive. CONCLUSIONS: When considered in conjunction with contrasting
      ancestral histories of exposure to TB, these observations suggest a difference in
      frequency of an innate ability to respond protectively to M. tuberculosis and to
      mount an effective mechanism to destroy it. This is best explained as a process
      of natural selection among largely separate heavily exposed ancestors. Several
      recent reports have identified genetically mediated mechanisms of immunity that
      could be involved with reduced vulnerability to tuberculosis. An understanding of
      these processes could aid in the development of immunomodulatory agents or
      vaccines.

PMID- 11573892
TI  - Surveillance of Mycobacterium tuberculosis drug resistance in Hong Kong, 1986
      1999, after the implementation of directly observed treatment.
AB  - OBJECTIVE: To study changing trends in TB epidemiology with emphasis on drug
      resistance rates in various age groups from 1986-1999. DESIGN: Laboratory-based
      data on drug susceptibility testing against streptomycin (SM), isoniazid (NH),
      rifampicin (RMP) and ethambutol (EMB) had been collected continuously in a
      centralised TB laboratory in Hong Kong. Epidemiological parameters such as sex,
      age and drug resistance rates in new and retreatment cases were measured and
      analysed for longitudinal trends. RESULTS: Of 48 924 non-duplicate isolates from
      new TB cases, 7045 (14.4%) were resistant to one or more drugs, 5773 (11.8%) were
      resistant to SM and/or INH while 881 (1.8%) were multidrug-resistant (MDR-TB). Of
      3857 isolates from retreatment patients, 1176 (30.5%) were resistant to one or
      more drugs, 616 (16.0%) were resistant to SM and/or [NH, and 467 (12.1%) were MDR
      TB. For isolates from new cases, significant declines were observed in the
      resistance rates against any drug, SM alone, INH alone, SM+INH and INH+RMP. For
      retreatment isolates, significant declines were also observed in resistance to
      any drug and INH+RMP. In both new and retreatment cases, isolates from patients
      aged over 65 years showed significantly lower drug resistance (any drug and
      INH+RMP) compared with other age groups (16-34 years and 35-65 years).
      CONCLUSION: With successful implementation of DOTS over a 14-year period,
      laboratory-based surveillance data showed significant declines in drug
      resistance, including MDR-TB. This has occurred amidst demographic changes
      associated with a generally ageing population as well as highly mobile sectors
      that are in constant exchange with highly endemic areas.

PMID- 11573893
TI  - Transmission of Mycobacterium tuberculosis among high school students in Korea.
AB  - SETTING: Screening of pulmonary tuberculosis (PTB) patients from high school
      students by chest radiography and sputum examination. OBJECTIVE: To investigate
      transmission of Mycobacterium tuberculosis among high school students. DESIGN:
      The restriction fragment length polymorphism (RFLP) profiles of M. tuberculosis
      isolated from PTB patients of high school students were analysed. RESULTS:
      Clustering cases were found in PTB patients screened among high school students.
      During this study, a single strain with a particular RFLP profile was found most
      frequently. This particular strain was also the one that was found to be most
      prevalent among Korean clinical isolates of M. tuberculosis during a nationwide
      TB prevalence survey previously done in 1995. This strain seems to be the most
      widely distributed one in Korea, and has thus been designated K1. In addition, by
      close examination of the RFLP profiles, it was also found that there existed 34
      isolates that had RFLP profiles that were similar to the K1 strain. Therefore, K1
      and K1-related strains (18.4% of strains, designated as the K family) seem to
      comprise the most dominant M. tuberculosis strains present in Korea. CONCLUSION:
      Clustering cases were found in PTB patients screened among high school students
      in Korea. The K family was found to be most prevalent among the clinical isolates
      of M. tuberculosis found.

PMID- 11573894
TI  - Childhood tuberculosis in the State of Qatar: the effect of a limited expatriate
      screening programme on the incidence of tuberculosis.
AB  - OBJECTIVE: To determine incidence rates and the effectiveness of the expatriate
      screening programme on paediatric tuberculosis (TB) in the State of Qatar.
      METHOD: A state-wide, population-based, retrospective analysis of all cases of
      tuberculosis among children 0-14 years of age reported to the TB Unit of the
      Division of Public Health during 1983-1996. RESULTS: One hundred and forty-four
      children with tuberculous disease were identified, with a steadily declining
      incidence rate (rate of notification) from 11/100000 children (0-14 years)
      population in 1983 to 7/100000 in 1996. This decrease in the childhood TB case
      notification rate correlated with foreign-born children, older children and the
      implementation of expatriate screening in 1986. Diagnosis in 56% of children was
      made abroad or within 3 months of arrival from vacation and 30% within one year
      of arrival. Comparison of the three age groups (<5, 5-9 and 10-14 years) showed
      no significant difference with regard to nationality, sex, type of TB,
      radiological findings and screening. However older children were more likely to
      be symptomatic (P < 0.0001) and to have positive tuberculin skin test (TST)
      reactivity (P = 0.012), culture (P < 0.0001), and gastric aspirates (P = 0.018).
      CONCLUSION: Although there was a 36% decrease in paediatric TB incidence after
      the implementation of expatriate screening in 1986, Qatar has a high rate of
      paediatric tuberculosis. The policy of BCG vaccination at birth should be
      continued, and screening children at school entry and on return from vacation
      would be useful for further case identification.

PMID- 11573895
TI  - Can guardians supervise TB treatment as well as health workers? A study on
      adherence during the intensive phase.
AB  - SETTING: In sub-Saharan Africa, tuberculosis (TB) has increased over the last two
      decades due to the human immunodeficiency virus pandemic. In Malawi, 20630 new TB
      patients were notified to the National Tuberculosis Programme in 1996, a fourfold
      increase since 1986. Due to this increase in cases and lack of resources (both
      human and monetary) it is becoming more difficult to ensure directly observed
      treatment (DOT) in the TB wards. METHODS: In Ntcheu district, Malawi, a new TB
      regimen was introduced from April 1996 in which patients received supervised
      treatment by either a health worker or a guardian (i.e., family member).
      Adherence to the different treatment options was measured by form checks, tablet
      counts, and tests for detecting isoniazid in the urine. Adherence was measured at
      2, 4 and 8 weeks after onset of TB treatment. RESULTS: Overall adherence rate was
      95-96%. Inpatients showed the highest adherence rates. Patients on guardian-based
      DOT (GB-DOT) (n = 35) showed 94% adherence, while patients on health centre based
      DOT (n = 40) showed more non-adherent behaviour: 11% according to monitoring
      forms, 14% according to tablet counts and 16% according to urine tests.
      DISCUSSION: The results suggest that decentralised care is a feasible option for
      anti-tuberculosis treatment and that guardians can supervise TB treatment just as
      well as health workers during the intensive phase of TB treatment.

PMID- 11573896
TI  - Compliance with cotrimoxazole prophylaxis for the prevention of opportunistic
      infections in HIV-positive tuberculosis patients in Thyolo district, Malawi.
AB  - OBJECTIVE: To verify compliance with cotrimoxazole prophylaxis in human
      immunodeficiency virus (HIV) infected tuberculosis (TB) patients during the
      continuation phase of anti-tuberculosis treatment, and to assess the sensitivity,
      specificity and positive predictive values of verbal verification and pill counts
      as methods of checking compliance. DESIGN: Cross-sectional study. METHODS:
      Cotrimoxazole compliance was assessed in a cohort of TB patients who were
      attending four TB follow-up centres during the continuation phase of anti-TB
      treatment between months 4 and 6. Verbal verification of drug intake, physical
      verification of pill count balance, and urine trimethoprim detection by gas
      chromatography and mass spectrometry were used for assessing compliance. RESULTS:
      Using urine trimethoprim detection as the gold standard for compliance,
      trimethoprim was detected in 82 (94%) of 87 patients in the cohort. Verbal
      verification of cotrimoxazole intake and objective pill count balances showed
      high sensitivity and positive predictive values compared with the gold standard
      of urine trimethoprim detection. CONCLUSIONS: In a rural district in Malawi,
      compliance with cotrimoxazole as an adjunct to anti-tuberculosis treatment in HIV
      infected TB patients was good, and can be assessed simply and practically by
      verbal verification and pill counts.

PMID- 11573897
TI  - 'Smear-negative' pulmonary tuberculosis in a DOTS programme: poor outcomes in an
      area of high HIV seroprevalence.
AB  - SETTING: Lilongwe Central Hospital, Malawi. OBJECTIVES: To investigate 1)
      treatment outcome of a cohort of smear-negative pulmonary TB (snPTB) patients in
      an area of high human immunodeficiency virus (HIV) seroprevalence, and 2) whether
      poor treatment outcomes are due to non-TB patients being mistakenly treated for
      TB due to lack of diagnostic facilities. DESIGN: Patients about to be registered
      for snPTB treatment by the National TB Programme underwent further assessment
      including TB culture, bronchoscopy and bronchoalveolar lavage. All patients were
      followed up for 8 months. Standard TB control treatment outcomes were recorded.
      RESULTS: Of 352 snPTB patients assessed, 137 patients had bacteriologically
      confirmed TB, 136 had possible TB, and 79 had other non-TB diagnoses. The HIV
      seroprevalence rate was 89%. Outcomes were known for 325 (92%) patients: 129
      (40%) died within 8 months. Death rates on TB treatment were 31% for
      bacteriologically confirmed TB patients and 35% for patients with possible TB but
      no bacteriological diagnosis. The death rate among patients with non-TB diagnoses
      was 53%. HIV infection significantly increased the risk of death (OR 3.9; P =
      0.01). CONCLUSION: SnPTB is strongly associated with HIV infection in Malawi,
      where patients treated for snPTB have a poor prognosis. The high mortality is not
      fully explained by non-TB patients being mistakenly treated for TB.

PMID- 11573898
TI  - Yield of smear, culture and amplification tests from repeated sputum induction
      for the diagnosis of pulmonary tuberculosis.
AB  - OBJECTIVES: To assess the yield of repeated sputum induction for the diagnosis of
      active tuberculosis in patients who do not produce spontaneous sputum, or with
      smear-negative spontaneous samples. METHODS: Induced sputum was examined with
      fluorescent microscopy, two amplification methods (PCR Amplicor MTB, and MTD2),
      and cultured for mycobacteria using liquid (Bactec 12B) and Lowenstein-Jensen
      media. Bronchoscopy and collection of other specimens were performed at the
      discretion of the treating physician. RESULTS: A total of 1115 sputum inductions
      performed in 500 patients without adverse events yielded an adequate specimen in
      1113 (99.8%), and microbiological confirmation in 43 of 44 (98%) culture-positive
      active TB cases. Yield increased with repeated sputum induction. The cumulative
      yield for acid-fast bacilli smear and mycobacterial culture was 64% and 70%
      respectively for one, 81% and 91% for two, 91% and 99% for three, and 98% and
      100% for four induced samples. Yield of PCR also increased with the greater
      number of induced samples tested. CONCLUSIONS: Repeated sputum induction could
      considerably improve diagnostic accuracy for pulmonary TB.

PMID- 11573899
TI  - False-positive growth of Mycobacterium tuberculosis attributable to laboratory
      contamination confirmed by restriction fragment length polymorphism analysis.
AB  - SETTING: Despite the high prevalence of tuberculosis in Korea, false-positive
      cultures have not yet been reported. At Pusan National University Hospital, in
      which positive mycobacterial culture specimens were 2.8 daily on average, 12
      specimens from 10 patients requested on the same day were positive for
      Mycobacterium tuberculosis. OBJECTIVE: To identify an episode of laboratory cross
      contamination in a tertiary care hospital. DESIGN: All isolates were analyzed by
      restriction fragment length polymorphism, and patients' medical records were
      reviewed. RESULTS: All isolates from 10 patients with supposed cross
      contamination were identical. Anti-tuberculosis drugs were administered to two
      patients unnecessarily, resulting in adverse drug reactions in one patient. In
      one patient who had known tuberculous empyema, the medication course was probably
      lengthened unnecessarily. CONCLUSIONS: An episode of laboratory cross
      contamination in mycobacterial cultures occurred, possibly due to droplets
      splashed from a sample in a centrifuge tube. Consequently, the aerosol soiled the
      tip of the dispenser and contaminated the following specimens sequentially. This
      episode of laboratory cross-contamination resulted in some modifications in our
      methods of specimen processing and interpretation of the results.

PMID- 11573900
TI  - Elevated soluble CD26 levels in patients with tuberculous pleurisy.
AB  - SETTING: Several reports have shown that tuberculous infection elicits a Th1-like
      immune response with increased levels of IFN-gamma. Recently, expression of CD26
      on CD4+ lymphocytes has been shown to correlate with the production of Th1-like
      cytokines. We therefore hypothesized that CD26 expression might increase in
      tuberculous pleural effusion, and might thus be a possible marker for detecting
      tuberculous pleurisy. OBJECTIVE AND DESIGN: To test this hypothesis, we measured
      soluble CD26 levels in the serum and pleural fluid of patients with tuberculous
      pleurisy (TB; n = 13), carcinomatous pleurisy (CA, n = 17), empyema (EM, n = 6),
      and congestive heart failure (HF, n = 10). RESULTS: The pleural CD26 levels, but
      not the serum CD26 levels, in patients with tuberculous pleurisy were
      significantly higher than those in other groups, and were correlated with levels
      of adenosine deaminase and interferon-gamma in the tuberculous pleural effusion.
      Furthermore, when the cut-off value for p-CD26 was set at 544.5 ng/ml, the
      positive rate for the TB group was significantly higher than that for the CA, EM
      and HF groups (P < 0.05). CONCLUSION: These results suggest that elevation of
      soluble CD26 in pleural fluid is implicated in Th1-like immune response, and may
      be a useful marker for tuberculous pleurisy.

PMID- 11573901
TI  - Counterattack of re-emerging tuberculosis after 38 years.
AB  - The recent tuberculosis prevalence rates in Japan have been among the highest in
      industrialised countries. In 1997 the number of newly identified tuberculosis
      patients in Japan increased for the first time in 38 years. There are many
      underlying reasons for this resurgence, including public ignorance of the threat,
      epidemiological factors, insufficient medical countermeasures, and inadequate
      public health measures against tuberculosis. Improving the situation will require
      urgent scientific and political action.

PMID- 11573902
TI  - Computed tomography and angiography in hepatic tuberculosis mimicking liver
      tumor.
AB  - Tuberculosis is one of the most common and well-documented infectious diseases,
      with a vast variety of clinical manifestations. A case of isolated hepatic
      tuberculosis mimicking liver tumor is presented. The patient was a 44-year-old
      man who had suffered from intermittent epigastralgia for about 2 years. Abdominal
      computed tomography demonstrated a low density mass with internal calcification
      over the left lobe of the liver. Celiac angiography showed encasement of the
      hepatic propia and occlusion of the left hepatic artery. Abnormal tortuous
      vascular structures were found at the hepatic hilar region. The patient underwent
      surgical intervention under the impression of left liver tumor. Microscopically,
      the resected liver tissue specimen revealed tuberculosis.

PMID- 11573903
TI  - Historical declines in tuberculosis: nature, nurture and the biosocial model.

PMID- 11573904
TI  - DOTS and DOTS plus: what's in a name.

PMID- 11573905
TI  - Efforts of the WHO/IUATLD to solve the problem of poor bioavailability of
      rifampicin from FDC anti-tuberculosis products: is a change required in the
      direction of the approach in view of recent findings?

PMID- 11573906
TI  - Free mediastinal air on chest CT scan: a diagnostic feature of esophageal
      tuberculosis in human immunodeficiency virus infection.

PMID- 11573907
TI  - What are we to think?

PMID- 11573908
TI  - Comparison of open and arthroscopic stabilization for recurrent shoulder
      dislocation in patients with a Bankart lesion.
AB  - We performed a prospective study of 117 patients (119 shoulders) with
      symptomatic, recurrent anterior posttraumatic shoulder instability to compare
      open versus arthroscopic reconstruction. Arthroscopic reconstructions (N = 66)
      were performed using bioabsorbable tacks (Suretac fixators), whereas open
      reconstructions (N = 53) were performed with suture anchors. All of the patients
      had a Bankart lesion. Independent observers examined 108 of the 119 shoulders
      (91%) at a median follow-up period of 28 months (range, 24 to 63) for the
      arthroscopic group and 36 months (range, 24 to 63) for the open group. The
      recurrence rate, including both dislocations and subluxations, was 9 of 60 (15%)
      in the arthroscopic group, compared with 5 of 48 (10%) in the open group. At
      follow-up, the Rowe score was 93 points (range, 39 to 100) and the Constant score
      was 91 points (range, 56 to 100) in the arthroscopic group, compared with 89
      points (range, 53 to 100 and 57 to 100 for the Rowe and Constant scores,
      respectively) for both scores in the open group. The only significant difference
      was in external rotation in abduction, which was 90 degrees (range, 50 degrees to
      135 degrees) in the arthroscopic group and 80 degrees (range, 25 degrees to 115
      degrees) in the open group. Both methods produced stable and well-functioning
      shoulders in the majority of patients.

PMID- 11573909
TI  - The meniscal "pseudocyst." A clinical sign of a torn meniscus.
AB  - We report a study of 636 patients requiring knee surgery, all of whom underwent
      detailed preoperative assessment. Fifty-eight patients had a clinical sign of a
      lump on the joint line when the knee was examined at 45 degrees of flexion, which
      has been thought to indicate a meniscal cyst. Of these 58 patients, however, only
      30 patients had a meniscal cyst demonstrated at surgery. The remaining 28
      patients had a meniscal tear without a cyst. In these 28 cases, the clinical sign
      of a lump protruding from the joint line was termed a "pseudocyst." This new
      clinical sign is important because of its frequency of occurrence and the
      complete correlation with meniscal tears requiring surgical intervention.

PMID- 11573910
TI  - Progressive loss of knee extension after injury. Cyclops syndrome due to a lesion
      of the anterior cruciate ligament.
AB  - Cyclops syndrome has been defined as a loss of knee extension due to impingement
      of a pedunculated proliferative tissue mass after anterior cruciate ligament
      reconstruction. We describe four patients who were operated on for progressive
      loss of knee extension after minor knee injury. During the arthroscopic
      procedure, the consistent finding was a fibrous pedunculated nodule adhering to
      the anterolateral aspect of the original anterior cruciate ligament, obstructing
      extension by impingement in the anterior aspect of the knee. At least part of the
      anterior cruciate ligament was intact in all cases. These patients were compared
      with seven patients who developed cyclops syndrome after anterior cruciate
      ligament reconstruction. Clinical and arthroscopic findings were the same in both
      groups. An arthroscopic excision of the nodule, performed an average of 12 weeks
      after knee trauma or after reconstruction, gave very good results. Histologic
      examination of the excised nodules from both groups showed fibroelastic
      connective tissue proliferation, thromboangiitis, and areas of necrotic bone and
      foreign body giant cell granuloma. On the basis of our observations, we conclude
      that formation of a fibrous pedunculated nodule may occur after an anterior
      cruciate ligament injury as well as after surgical reconstruction of the anterior
      cruciate ligament.

PMID- 11573911
TI  - The posteromedial impingement lesion of the ankle. A series of six cases.
AB  - We report on a series of six cases of posteromedial impingement lesion of the
      ankle operated on during a 3-year period with excellent or good results and a
      return of the patients to preinjury levels of activity. This lesion occurs, on
      occasion, after a severe ankle-inversion injury in which the deep posterior
      fibers of the medial deltoid ligament become crushed between the medial wall of
      the talus and the medial malleolus. Initially, posteromedial symptoms do not
      predominate, compared with the symptoms of the lateral ligament disruption, and
      they usually resolve without specific treatment. Occasionally, however, thick,
      disorganized fibrotic scar tissue persists and impinges between the medial wall
      of the talus and the posterior margin of the medial malleolus. Clinically, the
      patient has persistent medial to posteromedial activity-related ankle pain after
      a severe inversion injury, despite a sound ankle rehabilitation program. There is
      deep soft tissue induration immediately behind the medial malleolus with
      localized tenderness and reproduction of symptomatic pain on provocative testing
      by palpating this site while moving the ankle into plantar flexion and inversion.
      The posteromedial impingement lesion has a distinct pathologic picture and can
      coexist with other ankle lesions that cause pain after lateral ligament injury.

PMID- 11573912
TI  - Valgus laxity of the ulnar collateral ligament of the elbow in collegiate
      athletes.
AB  - In this investigation, we determined the patterns of valgus laxity and acquired
      valgus laxity of the ulnar collateral ligament in the elbows of collegiate
      athletes involved in overhead and nonoverhead sports. Acquired valgus laxity of
      the elbow is defined as the differential amount of stress valgus opening between
      the dominant and nondominant elbows. Forty-eight asymptomatic male athletes
      involved in sports that require overhead arm movements (baseball, tennis, and
      swimming) and 88 asymptomatic male athletes involved in nonoverhead sports
      (track, lacrosse, fencing, and wrestling) underwent fluoroscan examination of
      both their elbows with (13 daN) and without (0 N) valgus stress. There were no
      statistically significant differences in the amount of valgus stress opening or
      in acquired valgus laxity between the two groups. In fact, 25% (34 of 136) of the
      athletes showed an acquired valgus laxity of more than 0.5 mm, and 51.5% (70 of
      136) had an acquired valgus laxity that was actually negative. There was also no
      correlation between the number of years played and acquired valgus laxity. Our
      results show that acquired valgus laxity does not exist in asymptomatic athletes
      involved in overhead sports, and there is no threshold value of measurement
      indicative of acquired valgus laxity.

PMID- 11573913
TI  - Functional and radiographic outcome of juvenile osteochondritis dissecans of the
      knee treated with transarticular arthroscopic drilling.
AB  - Management of juvenile osteochondritis dissecans is controversial. The purpose of
      this study was to evaluate the functional and radiographic outcomes of
      transarticular arthroscopic drilling for isolated stable, juvenile
      osteochondritis dissecans lesions of the medial femoral condyle with an intact
      articular surface after 6 months of nonoperative management had failed. We
      reviewed 30 affected knees in 23 skeletally immature patients (mean age, 12.3
      years; range, 8.5 to 16.1) at an average follow-up of 3.9 years (range, 2.0 to
      7.2). Functional outcome was determined using the Lysholm score and radiographic
      outcome was determined using lesion size, and the radiographic score of
      Rodegerdts and Gleissner. There was significant improvement in the mean Lysholm
      score (from 58 to 93). There was significant improvement in the mean lesion size
      on anteroposterior (4.5 +/- 5.8 mm decrease) and lateral (8.4 +/- 8.1 mm
      decrease) radiographs. There was also significant improvement in the mean
      radiographic score (from 3.0 to 1.9). Radiographic healing was achieved in all
      patients at an average of 4.4 months after drilling (range, 1 to 11 months).
      Linear regression analysis revealed that younger age was an independent,
      multivariate predictor of Lysholm score improvement. There were no apparent
      surgical complications.

PMID- 11573914
TI  - The relationship between the angle of the tibial tunnel in the coronal plane and
      loss of flexion and anterior laxity after anterior cruciate ligament
      reconstruction.
AB  - Tension in an anterior cruciate ligament graft is greater with the knee in
      flexion when the angle of the tibial tunnel in the coronal plane is vertical or
      more perpendicular to the medial joint line of the tibia; however, the
      relationship of the angle of the tibial tunnel to knee function has not been
      studied. Greater graft tension may limit knee flexion or stretch the graft and
      increase anterior laxity. Five surgeons treated 119 subjects by reconstructing a
      torn anterior cruciate ligament using a double-looped semitendinosus and gracilis
      graft and a standardized technique. The femoral tunnel was drilled through the
      tibial tunnel. Radiographs were analyzed for tibial tunnel placement and a
      clinical evaluation was made 4 months postoperatively. Knees were assigned to
      subgroups according to the angle of the tibial tunnel in the coronal plane (65
      degrees to 69 degrees, 70 degrees to 74 degrees, 75 degrees to 79 degrees, 80
      degrees to 84 degrees, and 85 degrees to 89 degrees), with the angle of the
      latter subgroup being most vertical. Loss of flexion increased significantly from
      0.5 degrees to 6.5 degrees and anterior laxity increased significantly from 0.5
      to 2.2 mm as the tunnel angle was increased. The average angle of the tibial
      tunnel varied significantly, 11 degrees between surgeons (range, 69 degrees to 80
      degrees). We found a tibial tunnel angle of 75 degrees or more is associated with
      greater loss of flexion and anterior laxity. Surgeons do not drill the angle of
      the tibial tunnel in the coronal plane accurately. We now routinely drill the
      tibial tunnel at an angle of 65 degrees to 70 degrees in the coronal plane
      because it may reduce loss of flexion and anterior laxity.

PMID- 11573915
TI  - Comparison of torsional strengths of bioabsorbable screws for anterior cruciate
      ligament reconstruction.
AB  - The goals of this study were to evaluate torsional strength and modes of failure
      in commercially available bioabsorbable interference screws and to test the
      effect of screw diameter on torsional strength when screws become jammed during
      insertion. We tested the Arthrex, BioScrew, Endo-Fix, Phantom, and Sysorb screws,
      all 20 mm in length. Four major modes of failure were encountered. Analysis of
      variance revealed that both screw type and diameter had a significant effect on
      failure torque. The Endo-Fix 7-mm screw had the lowest failure torque (1.07 +/-
      0.18 N x m) and the Sysorb 8-mm screw had the highest (5.23 +/- 0.24 N x m). The
      Sysorb was significantly stronger than all the other screws. The failure torques
      were within the range that has been reported for manual screw insertion. We
      concluded that technical factors, which can affect insertion torque, assume
      particular importance with the use of bioabsorbable interference screws.

PMID- 11573916
TI  - The efficacy of wrist protectors in preventing snowboarding injuries.
AB  - Injuries of the wrist are common among snowboarders and in-line skaters. Wrist
      protectors have been developed to protect against injury. Some studies support
      the use of such wrist protection, but others emphasize the fact that wrist
      protectors may transfer the injury to other locations in the forearm. We
      conducted a prospective, randomized, clinical study of 5,029 snowboarders, 2,515
      in a braced group and 2,514 in a control group. The primary endpoint was fracture
      or sprain of the wrist with loss of range of motion and pain of at least a 3-day
      duration. Concomitant injuries were also recorded. Eight wrist injuries occurred
      in the braced group and 29 occurred in the control group. This was a significant
      difference. Beginners (first 5 days on a snowboard) and snowboarders with rented
      equipment were more prone to injury than others. No injuries could be related to
      the use of the wrist brace. We conclude that wrist braces are effective in
      protecting snowboarders against wrist injury. Beginners are a high-risk group.

PMID- 11573917
TI  - Prospective evaluation of arthroscopic stabilization of acute, initial anterior
      shoulder dislocations in young athletes. Two- to five-year follow-up.
AB  - From March 1992 to November 1998, 57 patients sustained 58 acute, initial,
      traumatic anterior shoulder dislocations at the United States Military Academy.
      Six patients selected nonoperative treatment. Three patients underwent primary
      open repair after diagnostic arthroscopy revealed no Bankart lesion amenable to
      repair with the bioabsorbable tissue tack. The remaining 48 patients with 49
      anterior dislocations were treated with arthroscopic primary repair. There were
      45 men and 3 women with an average age of 20 years (range, 17 to 23) and an
      average follow-up of 37 months (range, 24 to 60). The average Rowe score was 92
      (range, 30 to 100). The average single assessment numeric evaluation patient
      rating was 95.5% (range, 50% to 100%). The average Short Form-36 score (physical
      function) for the stable shoulders was 99 (range, 95 to 100). Forty-three
      shoulders remained stable (88%). There were six failures (12%). Factors
      associated with failure included a history of bilateral shoulder instability, a
      2+ sulcus sign, and poor capsulolabral tissue at the time of repair. All patients
      with stable shoulders returned to their preinjury levels of athletic activity.
      With follow-up of 5 years, we have observed significantly better results compared
      with nonoperative treatment in young, active adults at the United States Military
      Academy.

PMID- 11573918
TI  - Dynamic lateral patellar tilt in the anterior cruciate ligament-deficient knee. A
      magnetic resonance imaging analysis.
AB  - An open-configuration magnetic resonance imaging scanner was used to document
      patellar tracking abnormalities in 11 anterior cruciate ligament-injured knees.
      The contralateral normal knees were used as controls. Images were obtained with
      the quadriceps muscles at rest (knee flexion at 40 degrees, 25 degrees, and 10
      degrees) and with the quadriceps muscles contracted (knee flexion at 40 degrees
      and 25 degrees). When the quadriceps muscles were at rest there were no
      differences in patellar alignment between the anterior cruciate ligament-injured
      knees and the contralateral normal knees. When the quadriceps muscles were
      maximally contracted at 40 degrees of flexion, the patellae of the anterior
      cruciate ligament-injured knees tilted laterally 3.6 degrees relative to the
      resting state. When the quadriceps muscles were contracted at 25 degrees of
      flexion, the patellae of the anterior cruciate ligament-injured knees tilted
      laterally approximately 4 degrees relative to the resting state. Quadriceps
      active lateral patellar tilt at 25 degrees of flexion was greater in the anterior
      cruciate ligament-injured knees than in the contralateral normal knees, and it
      correlated with instrumented measurements of anterior tibial translation. Dynamic
      lateral patellar tilt during open kinetic chain exercises and during other
      activities that produce anterior tibial translation may contribute to extensor
      mechanism dysfunction in the anterior cruciate ligament-injured knee.

PMID- 11573919
TI  - Development and validation of the international knee documentation committee
      subjective knee form.
AB  - A committee of international knee experts created the International Knee
      Documentation Committee Subjective Knee Form, which is a knee-specific, rather
      than a disease-specific, measure of symptoms, function, and sports activity. The
      purpose of this study was to evaluate the reliability and validity of the new
      International Knee Documentation Committee Subjective Knee Form. To provide
      evidence for reliability and validity, we administered the final version of the
      form, along with the Short Form-36, to 533 patients with a variety of knee
      problems. Analyses were performed to determine reliability, validity, and
      differential item function related to age, sex, and diagnosis. Factor analysis
      revealed a single dominant component, making it reasonable to combine all
      questions into a single score. Internal consistency and test-retest reliability
      were 0.92 and 0.95, respectively. Based on test-retest reliability, the value for
      a true change in the score was 9.0 points. The International Knee Documentation
      Committee Subjective Knee Form score was related to concurrent measures of
      physical function (r = 0.47 to 0.66) but not to emotional function (r = 0.16 to
      0.26). Analysis of differential item function indicated that the questions
      functioned similarly for men versus women, young versus old, and for those with
      different diagnoses. In conclusion, the International Knee Documentation
      Committee Subjective Knee Form is a reliable and valid knee-specific measure of
      symptoms, function, and sports activity that is appropriate for patients with a
      wide variety of knee problems. Use of this instrument will permit comparisons of
      outcome across groups with different knee problems.

PMID- 11573920
TI  - Effect of screw length on bioabsorbable interference screw fixation in a tibial
      bone tunnel.
AB  - Initial tibial fixation strength is the weak link after anterior cruciate
      ligament reconstruction with a quadrupled hamstring tendon graft fixed with
      bioabsorbable interference screws. The purpose of this study was to determine the
      biomechanical differences between 28-mm and tapered 35-mm interference screws for
      tibial fixation of a soft tissue graft in 16 young cadaveric tibias. Failure
      mode, displacement before failure, and ultimate failure load were tested with a
      testing machine aligned with the tibial tunnel to simulate a worst-case scenario.
      The mode of failure was graft slippage past the screw in all but one of the
      specimens. The mean maximum load at failure of the 28-mm screw was 594.9 +/-
      141.0 N, with mean displacement at failure of 10.97 +/- 2.20 mm. The mean maximum
      load at failure of the 35-mm screw was 824.9 +/- 124.3 N, with a mean
      displacement to failure of 14.38 +/- 2.15 mm. The 38% difference in mean maximal
      load at failure was significant. Important variables in hamstring tendon graft
      fixation within a bone tunnel include bone mineral density, dilatation, gap size,
      screw placement, and screw width and length. Attention to these variables will
      help to provide secure graft fixation during biologic incorporation throughout
      the rehabilitation period.

PMID- 11573921
TI  - A multidisciplinary study of the healing of an intraarticular anterior cruciate
      ligament graft in a goat model.
AB  - We evaluated knee function, tensile properties, and histologic appearance of a
      healing intraarticular bone-patellar tendon-bone autograft after anterior
      cruciate ligament reconstruction in a goat model. The patellar tendon graft was
      fixed such that both bone-to-bone (femoral tunnel) and bone-to-tendon (tibial
      tunnel) healing could be studied. The total anteroposterior translation
      significantly increased from 3 to 6 weeks, ranging from increases of 28.8% to
      46.7%. In situ forces in the replacement graft decreased as much as 22.2% at 6
      weeks. Conversely, tensile properties of the femur-anterior cruciate ligament
      graft-tibia complex did not change significantly from 3 to 6 weeks. However, the
      mode of failure changed from the graft pulling out of the tibial tunnel at 3
      weeks to a mix of midsubstance failures (N = 2) and pullouts (N = 5) at 6 weeks.
      Histologic evaluations revealed progressive and complete incorporation of the
      bone block in the femoral tunnel, but only partial incorporation of the tendinous
      part of the graft in the tibial tunnel. The differences demonstrated at 3 and 6
      weeks may be a result of the remodeling process of the midsubstance of the graft
      as the interfaces within the osseous tunnels mature.

PMID- 11573922
TI  - The effect of ankle disk training on muscle reaction time in subjects with a
      history of ankle sprain.
AB  - The purpose of this study was to determine whether 8 weeks of ankle disk training
      alters ankle muscle onset latency of patients with a history of lateral ankle
      sprain. The training was completed by eight minimally symptomatic subjects with a
      history of nonrehabilitated, unilateral, inversion ankle sprain sustained between
      6 and 16 months before entry into the study. Ankle inversion perturbations
      monitored by fine-wire electromyography were performed in four lower extremity
      muscles (anterior tibialis, posterior tibialis, peroneus longus, and flexor
      digitorum longus) of all subjects on both the injured (experimental) and
      noninjured (control) legs. Testing was performed at study entry and after 8 weeks
      of ankle disk training on the previously injured ankle. Results revealed a
      statistically significant decrease in the anterior tibialis onset latency in both
      the experimental (67.6 +/- 20.3 to 51.7 +/- 17.6) and control (65.5 +/- 9.8 to
      53.8 +/- 23.7) ankles after the training period. These findings indicate that
      muscle onset latency decreases in specific ankle muscle groups after ankle disk
      training in previously injured ankles. Both the experimental and control ankles
      demonstrated a significant change, which raises the question as to whether a
      proprioceptive cross-training effect occurred.

PMID- 11573923
TI  - Effect of superior capsule and coracohumeral ligament release on strain in the
      repaired rotator cuff tendon. A cadaveric study.
AB  - Twelve cadaveric shoulders were used to determine the effects of release of the
      superior capsule and the coracohumeral ligament on the strain in the repaired
      rotator cuff tendon. A rotator cuff tear (2 cm wide and 1.5 cm long) was created
      and repaired under a 3-kg tensile force. The strain in the repaired tendon was
      measured with use of linear transducers with the arm in 50 different positions.
      Release of either the superior capsule or the coracohumeral ligament diminished
      the tension of the repaired rotator cuff by an average of 25% with the arm in
      adduction. Release of both of these structures further reduced the tension by an
      average of 44% in adduction and 43% to 60% with the arm in 15 degrees of
      elevation. The maximum reduction of tension in the repaired rotator cuff occurred
      when both the superior capsule and coracohumeral ligament were divided and when
      the arm was positioned in adduction and in 60 degrees of external rotation.
      Release of the coracohumeral ligament is equally as efficient as releasing the
      superior capsule in reducing the strain of the repaired rotator cuff. Releasing
      both structures seems to be desirable when releasing one structure or the other
      is not sufficient.

PMID- 11573924
TI  - Effects of knee bracing on the sensorimotor function of subjects with anterior
      cruciate ligament reconstruction.
AB  - The sensorimotor performance of the knee joint in 31 subjects who had undergone
      unilateral anterior cruciate ligament reconstruction at least 5 months previously
      was tested under three bracing conditions, 1) the DonJoy Legend brace, 2) a
      mechanical placebo brace, and 3) no brace, in random order. The accuracy of the
      subjects' ability to reproduce specified knee joint angles was tested as well as
      the isokinetic performance of their knee muscles at 60 and 180 deg/sec. The
      results showed that subjects with the brace or placebo brace performed similarly
      in reproducing the knee joint positions, but both groups performed better than
      the subjects without a brace. Isokinetic tests revealed no difference among the
      three groups in extensor and flexor peak torque production at 60 deg/sec or total
      work done by the extensors and flexors at 60 and 180 deg/sec. These results
      suggest that knee bracing can improve the static proprioception of the knee
      joint, but not the muscle contractile function, in subjects with anterior
      cruciate ligament reconstruction under isokinetic testing conditions. The finding
      of similar performances for joint angle reproduction in the brace and placebo
      brace groups suggests that the apparent improvement in proprioception with knee
      bracing was not due to the mechanical restraining action of the brace.

PMID- 11573925
TI  - A knotless suture anchor. Design, function, and biomechanical testing.
AB  - The development of a unique Knotless suture anchor for soft tissue repair to bone
      is described. This device allows for soft tissue repair to bone using a suture
      anchor without the need for knot tying. This provides a particular advantage for
      arthroscopic repairs, where knot tying can be difficult. The Knotless suture
      anchor has a short loop of suture secured to the tail end of the anchor. A
      channel located at the tip of the anchor functions to capture the loop of suture
      after it has been passed through the soft tissue. The soft tissue is tensioned as
      the anchor is inserted into bone to the appropriate depth. Biomechanical testing
      demonstrated increased suture strength in the Knotless suture anchor compared
      with standard suture anchors. This is because of the doubled-suture configuration
      that is created with the Knotless suture anchor loop. To the author's knowledge,
      this paper describes the first knotless suture anchor. A secure, low-profile
      repair can be created without knot tying.

PMID- 11573926
TI  - Osteochondral grafting and arthroplasty for end-stage osteochondritis dissecans
      of the capitellum. A case report and review of the literature.

PMID- 11573927
TI  - Dislocation of the posterior tibial tendon without disruption of the flexor
      retinaculum. A case report and review of the literature.

PMID- 11573928
TI  - Spontaneous healing of a bucket-handle lateral meniscal tear in an anterior
      cruciate ligament-deficient knee. A case report.

PMID- 11573929
TI  - Motion loss after ligament injuries to the knee. Part I: causes.
AB  - Motion loss continues to be a difficult complication after ligament injury and
      surgery to the knee. A better understanding of the pathoanatomic causes of motion
      loss can lead to improved prevention and treatment strategies. When motion loss
      does occur, early recognition and appropriate treatment can be expected to
      restore motion and improve function in most patients. Treatment options, although
      varied, should improve outcome when implemented appropriately. This article is
      composed of two parts. The first part reviews the current concepts on
      definitions, incidence, and causes of motion loss. In the second part, to be
      published later, current strategies on prevention and treatment of motion loss
      after ligament injury to the knee are reviewed. Emphasis is placed on risk
      factors and prevention as well as on diagnosis and treatment. The article
      summarizes the latest information from the basic sciences as well as clinical
      studies on the problem of motion loss of the knee and attempts to provide a
      rational approach to these difficult clinical problems.

PMID- 11573930
TI  - Upper extremity snowboarding injuries: ten-year results from the Colorado
      Snowboard Injury Survey.

PMID- 11573931
TI  - The incidence of patellofemoral osteoarthritis and associated findings 7 years
      after anterior cruciate ligament reconstruction with a bone-patellar tendon-bone
      autograft.

PMID- 11573932
TI  - ATP synthase motor components: proposal and animation of two dynamic models for
      stator function.
AB  - Recent research indicates that ATP synthases (F(0)F(1)) contain two distinct
      nanomotors, one an electrochemically driven proton motor contained within F(0)
      that drives an ATP hydrolysis-driven motor (F(1)) in reverse during ATP
      synthesis. This is depicted in recent models as involving a series of events in
      which each of the three alphabeta pairs comprising F(1) is induced via a
      centrally rotating subunit (gamma) to undergo the sequential binding changes
      necessary to synthesize ATP (binding change mechanism). Stabilization of this
      rotary process (i.e., to minimize "wobble" of F(1)) is provided in current models
      by a peripheral stalk or "stator" that has recently been shown to extend from
      near the bottom of the ATP synthase molecule to the very top of F(1). Although
      quite elegant, these models envision the stator as fixed during ATP synthesis,
      i.e., bound to only a single alphabeta pair. This is despite the fact that the
      binding change mechanism views each alphabeta pair as going through the same
      sequential order of conformational changes which demonstrate a chemical
      equivalency among them. For this reason, we propose here two different dynamic
      models for stator function during ATP synthesis. Both models have been designed
      to maintain chemical equivalency among the three alphabeta pairs during ATP
      synthesis and both have been animated.

PMID- 11573933
TI  - Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human
      kidney: suppression of HIF-mediated gene expression by HIF-3alpha.
AB  - Hypoxia inducible factors (HIFs) are heterodimeric transcription factors that
      regulate a number of adaptive responses to low oxygen tension. They are composed
      of alpha- and beta-subunits that belong to the basic helix-loop-helix-PAS
      superfamily. Here we examined the expression of HIF-alpha subunit proteins in the
      human kidney and found that, in addition to HIF-1alpha and -2alpha, HIF-3alpha
      was also expressed. The sequence analysis revealed that, like mouse HIF-3alpha,
      human HIF-3alpha has high similarity with HIF-1alpha and -2alpha in the bHLH and
      PAS domains, but lacks structures for transactivation found in the C-terminus of
      HIF-1alpha and -2alpha. Furthermore, we performed reporter gene analysis and
      showed that HIF-3alpha suppresses hypoxia-inducible HIF-mediated gene expression.
      HIF-3alpha might be a negative regulator of hypoxia-inducible gene expression in
      the human kidney.

PMID- 11573934
TI  - Cloning of a new aquaporin (AQP10) abundantly expressed in duodenum and jejunum.
AB  - A new aquaporin (AQP10) was identified in human small intestine. This gene
      encoded a 264-amino-acid protein with high sequence identity with AQP3 (53%), 9
      (52%), and 7 (43%). These AQPs constitute one subfamily of AQP family that is
      differentiated from the other subfamily of AQP (AQP0, 1, 2, 4, 5, 6, and 8) by
      sequence homology. Ribonuclease protection assay and Northern blotting
      demonstrated almost exclusive expression of AQP10 mRNA in the duodenum and
      jejunum. In situ hybridization localized it in absorptive jejunal epithelial
      cells. Xenopus oocytes expressing AQP10 exhibited an increased osmotic water
      permeability in a mercury-sensitive manner. Although AQP10 belongs to the AQP
      subfamily, which has been characterized by permeability to water and neutral
      solutes such as urea and glycerol, it was not permeable to urea nor glycerol. The
      specific expression of AQP10 suggests its contribution to the water transport in
      the upper portion of small intestine.

PMID- 11573935
TI  - Studies on transcriptional regulation of Cyp3a16 gene in mouse livers by
      application of direct DNA injection method.
AB  - CYP3A16 is expressed in the mouse liver specifically during a fetal and puberty
      life. Functional regions responsible for the transcriptional regulation of the
      Cyp3a16 gene were identified by an in vivo direct DNA injection into mouse livers
      followed by a luciferase assay. The results of the deletion analysis of a 5'
      flanking sequence suggested the existence of an adult-specific repressor(s)
      interacting with the Cyp3a16 gene. In addition, a positive regulatory element was
      assumed to be present in a region from -146 to -56 of the Cyp3a16 gene. A
      hepatocyte nuclear factor 4 (HNF-4)-binding consensus sequence was found in this
      region. In fact, HNF-4alpha bound to this sequence as evidenced by a gel mobility
      shift assay. The role of the HNF-4-binding sequence was further examined by an
      introduction of mutations in this sequence. The introduction of the mutations
      resulted in a reduced activity of a luciferase in the assay. These results
      obtained by an application of the direct DNA injection method suggest that the
      HNF-4alpha activates the transcription of the Cyp3a16 gene in vivo.

PMID- 11573936
TI  - A disulfide bond is required for functional assembly of NCX1 from complementary
      fragments.
AB  - The cardiac Na(+)-Ca(2+) exchanger consists of a single polypeptide with two
      transmembrane segment (TMS) clusters separated by a large intracellular loop
      between TMS5 and TMS6 (Nicoll et al. (1999) J. Biol. Chem. 274, 910-917; Iwamoto
      et al. (1999) FEBS Lett. 446, 264-268). A "split" exchanger can be expressed by
      dividing the exchanger cDNA into two fragments so that the NH(2)- and CO(2)H
      terminal portions of the protein are expressed as separate polypeptides in HEK293
      cells. Expression of partial exchanger molecules did not result in detectable
      exchanger activity. Cells coexpressing both portions of the exchanger, however,
      displayed between 30 and 50% of the activity of the intact wild-type exchanger.
      The full-length exchanger contains a disulfide bond between residues 14 or 20 and
      792. We examined the role of this disulfide bond in the split exchanger by
      mutagenesis and expression studies. Our results indicate that the function of the
      exchanger requires both TMS clusters and that the C(14 or 20)/C792 disulfide bond
      is essential for expression of active exchangers from half molecules.

PMID- 11573937
TI  - Hepatotoxin rubratoxin B induced the secretion of TNF-alpha, IL-8, and MCP-1 in
      HL60 cells.
AB  - Induction of cytokine secretion by rubratoxin B was investigated using HL60
      cells. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 were secreted
      from 40 and 80 microg/ml rubratoxin B-treated cells. In 20 and 40 microg/ml
      rubratoxin B-treated samples, monocyte chemotactic protein (MCP)-1 was released.
      These rubratoxin B-induced cytokines are known to promote liver myelocytic cell
      infiltration, and activate cytokine-recruited cells. As a result, recruited
      myelocytic cells are considered to contribute to hepatic injury. We investigated
      the effects of tyrosine kinase inhibitors genistein and emodin. Genistein reduced
      the release of all three cytokines from rubratoxin B-treated cells. Likewise,
      emodin diminished the secretion of MCP-1. Alternatively, emodin reversed on the
      secretion of TNF-alpha, and the release of IL-8 was not affected. Since emodin
      did not impede rubratoxin B-caused TNF-alpha and IL-8 secretion, they appeared to
      be regulated differently from MCP-1 secretion, suggesting that rubratoxin B
      exerts its toxicity using two or more signal transduction pathways.

PMID- 11573938
TI  - Role of acidic amino acid residues of PsaD subunit on limiting the affinity of
      photosystem I for ferredoxin.
AB  - The PsaD subunit of photosystem I is one of the central polypeptides for the
      interaction with ferredoxin, its acidic electron acceptor. In the cyanobacterium
      Synechocystis 6803, this role is partly performed by a sequence extending
      approximately from histidine 97 to arginine 119, close to the C-terminus. In the
      present work, acidic amino acids D100, E105, and E109 are shown to moderate the
      affinity of Photosystem I for ferredoxin. Most single replacements of these
      residues by neutral amino acids increased the affinity for ferredoxin, resulting
      in a dissociation constant as low as 0.015 microM for the E105Q mutant (wild-type
      K(D) = 0.4 microM). This is the first report on the limitation of photosystem I
      affinity for ferredoxin due to acidic amino acids from PsaD subunit. It
      highlights the occurrence of a negative control on the binding during the
      formation of transient complexes between electron carriers.

PMID- 11573939
TI  - Properties of the cysteine-less Pho84 phosphate transporter of Saccharomyces
      cerevisiae.
AB  - The derepressible Pho84 high-affinity phosphate permease of Saccharomyces
      cerevisiae, encoded by the PHO84 gene belongs to a family of phosphate:proton
      symporters (PHS). The protein contains 12 native cysteine residues of which five
      are predicted to be located in putative transmembrane regions III, VI, VIII, IX,
      and X, and the remaining seven in the hydrophilic domains of the protein. Here we
      report on the construction of a Pho84 transporter devoid of cysteine residues (C
      less) in which all 12 native residues were replaced with serines using PCR
      mutagenesis and the functional consequences of this. Our results clearly
      demonstrate that the C-less Pho84 variant is able to support growth of yeast
      cells to the same extent as the wild-type Pho84 and is stably expressed under
      derepressible conditions and is fully active in proton-coupled phosphate
      transport across the yeast plasma membrane.

PMID- 11573940
TI  - A new stroke marker as detected by serum phosphoglycerate mutase B-type isozyme.
AB  - The diagnostic significance of phosphoglycerate mutase (PGM) B-type isozyme
      activity capable of being inducible under hypoxia at the gene level as a serum
      marker for cerebral stroke was investigated. The normal level (mean +/- 2 SD) in
      human serum was determined to be 38 +/- 18 units/L. Within 2 h after the onset of
      cerebral stroke (n = 65), B-type isozyme activity was elevated to 68 +/- 36
      units/L, and retained to be higher level until 1-3 days. Serum B-type isozyme
      activities of 52 survival cases and 13 dead cases, being judged at the period of
      1-2 months after the onset, were retrospectively compared; B-type isozyme
      activity that had been measured within 24 h after the onset was significantly
      higher (81 +/- 42 units/L) for the dead cases than for survival cases (57 +/- 27
      units/L) with P < 0.05. These results suggest that serum PGM B-type isozyme has
      the potential as a novel marker for diagnosis of cerebral stroke and its
      severity.

PMID- 11573941
TI  - Effect of temperature on enzymatic and physiological factors related to chilling
      injury in carambola fruit (Averrhoa carambola L.).
AB  - Three groups of carambola fruits (Averrhoa carambola L.) were stored at 2 and 10
      degrees C (85-90% relative humidity). The major physicochemical, physiological,
      and enzymatic responses of fruit were measured in each group over a 30-day
      period: chilling injury index (CII), decay (%), intracuticular waxes, cuticle
      permeability, pulp firmness, weight loss, sucrose, fructose and glucose contents,
      ion electrolyte leakage in pulp (%), ethylene and carbon dioxide production
      rates, and the activities of peroxidase (POD), polyphenol oxidase (PPO), and
      phenylalanine ammonia-lyase (PAL) enzymes. CII values were statistically
      different at 2 and 10 degrees C, showing high significance with respect to
      sucrose content and weight loss (P < 0.05). Chilling injury included darkened
      ribs and skin desiccation. According to the CI symptom development, a possible
      relationship of POD and PPO activities was found at 2 degrees C. A significant
      sucrose content increase was observed at 10 degrees C. CI symptoms were
      associated with POD and PAL activities.

PMID- 11573942
TI  - Hormone response of rodent phenylalanine hydroxylase requires HNF1 and the
      glucocorticoid receptor.
AB  - Expression of the rodent phenylalanine hydroxylase (PAH) gene is dependent upon
      hormones. Induction by glucocorticoids and cAMP occurs slowly and maximal
      stimulation is obtained by a synergistic effect of the two compounds. Hormone
      responsiveness is conferred by the tissue-specific HSIII enhancer and involves
      (i) protein kinase A mediating the cAMP response, even though a consensus
      sequence for binding of the cAMP response element binding protein is not present;
      (ii) other serine/threonine kinases as deduced from inhibitor studies; (iii)
      glucocorticoid receptor protein bound to glucocorticoid response element half
      sites; and (iv) binding of the liver-enriched transcription factor hepatocyte
      nuclear factor 1 (HNF1) to sites in the enhancer. Glucocorticoid receptor and
      HNF1, bound to their cognate sites, cooperatively increase the glucocorticoid
      response of the PAH gene, this response being synergistically enhanced by cAMP
      after long-term treatment.

PMID- 11573943
TI  - Characterization and identification of exflagellation-inducing factor in the
      salivary gland of Anopheles stephensi (Diptera: Culicidae).
AB  - Gamete activation factor (GAF) induces exflagellation of Plasmodium microgametes.
      We found GAF in the salivary glands of female mosquitoes, Anopheles stephensi.
      The exflagellation was induced in a concentration-dependent manner in the
      supernatant of salivary gland's crude homogenate. The exflagellation-inducing
      activity in the salivary gland was higher than that in the midgut and the head.
      GAF in the salivary glands was found to be heat stable and low molecular weight
      (<3000 molecular weight). Analysis of the supernatant by capillary
      electrophoresis and UV absorbance profile showed that the salivary glands
      contained xanthurenic acid, which was previously identified as GAF in the head of
      A. stephensi. The exflagellation-inducing activity in the salivary gland declined
      immediately after a blood meal, implying that GAF was in the saliva, and was
      delivered into the midgut together with the blood and induced exflagellation in
      the midgut.

PMID- 11573944
TI  - Disruption of replication protein A/single-stranded DNA complexes during
      apoptosis in HL-60 cells.
AB  - Replication protein A (RPA) is a single-stranded DNA-binding protein which plays
      a role in DNA replication, repair, and recombination. We used gel mobility shift,
      super gel mobility shift, and Western blot to determine the fate of RPA during
      Hoechst 33342-induced apoptosis in HL-60 cells. Multiple bands were detected by
      gel mobility shift after the incubation of single-stranded gamma-(32)P-labeled
      oligo(dT)(30) with the nuclear extracts of HL-60 cells. Super gel mobility shift
      results indicated that only the highest molecular weight protein/oligo(dT)(30)
      complexes bound with anti-human RPA-32 and/or anti-human RPA-70 antibodies
      forming RPA/oligo(dT)(30) complexes. After the treatment of HL-60 cells with 15
      microg/ml Hoechst 33342 for 3 h, the bands of RPA/oligo(dT)(30) complexes were
      decreased and bands of the lowest molecular weight protein/oligo(dT)(30)
      complexes were significantly increased when compared to the control group. These
      low-molecular-weight bands did not bind with RPA-32 or RPA-70 antibodies. Western
      blotting results showed that both RPA-32 and RPA-70 were decreased significantly
      in a time-dependent manner after 1 h of incubation with Hoechst 33342. These
      results demonstrate that in HL-60 cells, Hoechst 33342-induced apoptosis is
      associated with a rapid loss of the binding capacity of RPA to oligo(dT)(30) as
      well as immunoactive RPA-70 and RPA-32.

PMID- 11573945
TI  - Neomycin inhibits the angiogenic activity of fibroblast and epidermal growth
      factors.
AB  - Neomycin has been shown to block nuclear translocation of angiogenin in
      endothelial cells, thereby inhibiting its capacity to induce angiogenesis. We
      report here that neomycin is also an effective inhibitor of angiogenesis induced
      by acidic fibroblast growth factor, basic fibroblast growth factor, and epidermal
      growth factor, all of which undergo nuclear translocation, but not that of
      vascular endothelial growth factor which does not undergo nuclear translocation.
      Blocking nuclear translocation, therefore, seems to be a general mechanism for
      the antiangiogenesis action of neomycin applicable to those angiogenic factors
      that require nuclear translocation for angiogenesis. These results along with the
      known toxicity and pharmacokinetics profiles make neomycin and its analogues good
      candidate inhibitors of angiogenesis that might be developed as antitumor agents.

PMID- 11573946
TI  - Novel immuno-FRET assay method for Bacillus spores and Escherichia coli O157:H7.
AB  - Novel immunofluorescence resonance energy transfer (immuno-FRET) assays for both
      Bacillus cereus spores and Escherichia coli O157:H7 are reported. Both assays
      involve the use of dual (QSY-7 and Oregon Green 514-antibody)-labeled spores or
      vegetative bacteria, such that Oregon Green 514-labeled antibodies are quenched
      by proximal QSY-7 molecules that are covalently bound to the dual (Oregon Green
      514 and QSY-7)-labeled cells. Upon introduction of unlabeled bacteria or spores,
      in the respective assays, an increase in fluorescence is observed in proportion
      to the numbers of unlabeled cells. This is due to migration of Oregon Green 514
      labeled antibody from the dual-labeled cells to the unlabeled target cells as
      verified by fluorescence microscopy. Optimization of the QSY-7 surface density
      led to a B. cereus spore detection sensitivity of approximately 1.0 x 10(5) to
      2.5 x 10(5) spores per milliliter and 3.5 x 10(5) cells per milliliter for E.
      coli using a conventional cuvette-based spectrofluorometer.

PMID- 11573947
TI  - sPLA(2) cooperates with cPLA(2)alpha to regulate prostacyclin synthesis in human
      endothelial cells.
AB  - The first step in prostacyclin (PGI(2)) synthesis involves the generation of
      arachidonic acid (AA) from membrane phospholipids mediated by the 85 kDa
      cytosolic phospholipase A(2) (cPLA(2)alpha). The current study examined the
      effects of secretory PLA(2)s (sPLA(2)s) on PGI(2) production by human umbilical
      vein endothelial cells (HUVEC). We demonstrate that exposure of HUVEC to sPLA(2)
      dose- and time-dependently enhances AA release and PGI(2) generation. sPLA(2)
      stimulated AA mobilisation was blocked by AACOCF(3), an inhibitor of
      cPLA(2)alpha, suggesting cross-talk between the two classes of PLA(2). sPLA(2)
      induced the phosphorylation of cPLA(2)alpha and enhanced the phosphorylation
      states of p42/44(mapk), p38(mapk), and JNK, concomitant with elevated AA and
      PGI(2) release. The MEK inhibitor PD98059 attenuated sPLA(2)-stimulated
      cPLA(2)alpha phosphorylation and PGI(2) release. These data show that sPLA(2)
      cooperates with cPLA(2)alpha in a MAPK-dependent manner to regulate PGI(2)
      generation and suggests that cross-talk between sPLA(2) and cPLA(2)alpha is a
      physiologically important mechanism for enhancing prostanoid production in
      endothelial cells.

PMID- 11573948
TI  - Ascorbate-induced high-affinity binding of copper to cytosolic proteins.
AB  - Copper chaperones are necessary for intracellular trafficking of copper to target
      proteins. This is probably because the milieu inside the cell has a large
      capacity for sequestering this metal. By fluorometry using a fluorescent Cu(II)
      chelator and by centrifugal ultrafiltration, we have studied copper binding of
      the whole cytosolic proteins from mouse brain and liver, and found that their
      binding capacity and affinity for copper were markedly increased by ascorbate.
      Brain cytosolic protein bound, with high affinity, 63 nmol of copper/mg, more
      than half of which was redox-inactive, as indicated by its inability to catalyze
      oxidation of ascorbate. Most of the bound copper was in the Cu(I) state,
      coordinating to thiol groups of protein. Cytosolic protein competed for copper
      more strongly than GSH when compared at their relative concentrations in tissues.
      The results taken together suggest that protein thiols of cytosol can strongly
      sequester copper.

PMID- 11573949
TI  - Inhibition of NFkappaB induces caspase-independent cell death in human T
      lymphocytes.
AB  - Nuclear factor kappaB (NFkappaB) regulates the expression of various genes
      essential for cell survival. Here we demonstrate that suppression of NFkappaB
      nuclear import with SN50 peptide carrying the nuclear localization sequence (NLS)
      of the NFkappaB p50 subunit induces apoptosis in human peripheral blood T
      lymphocytes (T-PBL), which can be blocked with the pan-caspase inhibitor Z
      VAD.fmk. However, even when caspase function is blocked, the addition of SN50
      induces irreversible cell loss due to the reduction in the mitochondrial
      transmembrane potential (DeltaPsim) followed by disruption of the cell membrane,
      hallmarks of necrosis. These observations demonstrate that although inhibition of
      NFkappaB nuclear translocation by SN50 peptide can induce caspase-dependent
      apoptosis in T-PBL, cell death may still proceed in the absence of functional
      caspase activity. The availability of downstream caspases appears to determine
      the mode of cell death in NFkappaB defective cells.

PMID- 11573950
TI  - Novel fibroblast growth factor 2 transcripts are expressed in mouse embryos.
AB  - We have discovered two new exons in the mouse fibroblast growth factor 2 (FGF-2
      or bFGF) gene that can be alternatively spliced to the second coding exon of the
      gene. The newly identified exons 1b and 1c are located at, respectively,
      approximately 19 and 32 kb downstream of the canonical exon 1a. Using RT-PCR
      analysis, mRNAs containing exon 1c and canonical exons 2 and 3 were identified in
      embryonic limb, placenta, face, carcass and ocular tissues. A 3.7-kb transcript
      present in placenta and embryonic limb hybridizes with an exon 1c-derived probe
      in Northern blot analysis. Alternative splicing of exon 1c to exon 2 creates a
      transcript for which the predicted alternative FGF-2 (altFGF-2) polypeptide
      contains a novel N-terminal domain. Our data indicate that in mouse embryos
      multiple novel mRNA variants are transcribed from the FGF-2 locus using
      alternative splicing. These data suggest that proteins arising from these
      alternative transcripts may play a role in mouse embryogenesis.

PMID- 11573951
TI  - Autocrine role of macrophage inflammatory protein-1 beta in human T-cell
      lymphotropic virus type-I tax-transfected Jurkat T-cells.
AB  - The interaction of human T-cell lymphotropic virus I (HTLV-I) tax gene with host
      cell factors plays an important role in the maintenance of the transformed state.
      There have been numerous reports that have demonstrated the role of tax in
      transactivating several cytokines. In this study, we show that upon mitogen
      stimulation, macrophage inflammatory protein-1 beta (MIP-1beta) is expressed and
      secreted in tax-transfected Jurkat cells. Furthermore, expression of CC-chemokine
      receptor-5 (CCR5) mRNA in these cells suggests an autocrine role for MIP-1beta in
      HTLV-I-infected T-cells. These results, coupled with our earlier observations,
      demonstrate the influence that extracellular Tax protein might have on modulating
      host chemokines for proliferation and transformation of uninfected cells.

PMID- 11573952
TI  - Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of
      apigenin in normal versus human prostate carcinoma cells.
AB  - Agents that are capable of inducing selective apoptosis of cancer cells are
      receiving considerable attention in developing novel cancer-preventive
      approaches. In the present study, employing normal human prostate epithelial
      cells (NHPE), virally transformed normal human prostate epithelial cells (PZ-HPV
      7), and human prostate adenocarcinoma (CA-HPV-10) cells, we evaluated the growth
      inhibitory effects of apigenin, a flavonoid abundantly present in fruits and
      vegetables. Apigenin treatment to NHPE and PZ-HPV-7 resulted in almost similar
      growth inhibitory responses of low magnitude. In sharp contrast, apigenin
      treatment resulted in a significant decrease in cell viability of CA-HPV-10
      cells. Similar selective growth inhibitory effects were also observed for human
      epidermoid carcinoma A431 cells compared to normal human epidermal keratinocytes.
      Apigenin treatment resulted in significant apoptosis of CA-HPV-10 cells as
      evident from (i) DNA ladder assay, (ii) fluorescence microscopy, and (iii) TUNEL
      assay, whereas the NHPE and PZ-HPV-7 cells did not undergo apoptosis but showed
      exclusive necrotic staining only at a high dose of 40 microM. Apigenin (1-10
      microM) also resulted in a dose-dependent G2-M phase cell cycle arrest of CA-HPV
      10 cells but not of PZ-HPV-7 cells. The growth-inhibitory and apoptotic potential
      of apigenin was also observed in a variety of prostate carcinoma cells
      representing different stage and androgen responsiveness. Apigenin may be
      developed as a promising chemopreventive and/or chemotherapeutic agent against
      prostate cancer.

PMID- 11573953
TI  - Functional analysis of the transcriptional activity of the mouse phospholipid
      transfer protein gene.
AB  - Phospholipid transfer protein (PLTP) plays an important role in the metabolism of
      plasma high density lipoprotein. The mouse gene encoding PLTP and its promoter
      region has been cloned in our laboratory. The present study was conducted to
      functionally analyze the transcriptional regulation of the mouse PLTP gene. The
      results indicated that DNA sequences between -245 and -69 were responsible for
      the full promoter activity and binding motifs for transcription factor Sp1 and AP
      2 within this functional promoter region were synergistically essential for the
      basal transcription. The transcriptional activity of this gene was significantly
      increased by chenodeoxycholic acid and fenofibrate, suggesting that transcription
      factor farnesoid X-activated receptor (FXR) and peroxisome proliferator-activated
      receptor (PPAR) are likely involved in the transcriptional regulation. DNA
      sequence analysis suggests that DNA sequences from -407 to -395 and from -393 to 
      381 are homologous to the recognition motifs of FXR, and those from -859 to -847
      and from -309 to -297 are similar to the potential binding motif for PPAR. These
      findings provide a molecular basis for further investigation of the physiological
      function and regulation of the PLTP gene in mice.

PMID- 11573954
TI  - Dynorphin A inhibits nociceptin-converting enzyme from the rat spinal cord.
AB  - Cysteine proteinase found in the spinal cord of rat, called nociceptin-converting
      enzyme (NCE), is competitively inhibited by dynorphin A and its fragment des
      [Tyr(1)]-DYN A. This proteinase converts orphanin FQ/nociceptin (OFQ/N) to two
      major fragments: OFQ/N(1-11) and further OFQ/N(1-6) with analgesic properties.
      Dynorphin A at the concentration of 10 microM increases K(M) from 15.0 to 55.9
      microM. The calculated K(i) for this interaction was estimated at 3.7 microM.
      This observation may suggest an interaction between opioid and nociceptive
      systems which may be affected by the balance between opioid and antiopioid
      systems. This balance between particular OFQ/N sequences that are derived from
      the same precursor and regulated by proteinases may play an important role in
      pain. Interestingly, dynorphin B does not reveal a similar action on the NCE.

PMID- 11573955
TI  - The J domain of Tpr2 regulates its interaction with the proapoptotic and cell
      cycle checkpoint protein, Rad9.
AB  - Human Rad9 is a key cell-cycle checkpoint protein that is postulated to function
      in the early phase of cell-cycle checkpoint control through complex formation
      with Rad1 and Hus1. Rad9 is also thought to be involved in controlling apoptosis
      through its interaction with Bcl-2. To explore the biochemical functions of Rad9
      in these cellular control mechanisms, we performed two-hybrid screening and
      identified Tetratricopeptide repeat protein 2 (Tpr2) as a novel Rad9-binding
      protein. We found that Tpr2 binds not only to Rad9, but also to Rad1 and Hus1,
      through its N-terminal tetratricopeptide repeat region, as assessed by in vivo
      and in vitro binding assays. However, the in vivo and in vitro interactions of
      Tpr2 with Rad9 were greatly enhanced by the deletion of its C-terminal J domain
      or by a point mutation in the conserved HPD motif in the J domain, though the
      binding of Tpr2 to Rad1 and Hus1 was not influenced by these J-domain mutations.
      We further found: (1) Rad9 transiently dissociates from Tpr2 following heat-shock
      or UV treatments, but the mutation of the J domain abrogates this transient
      dissociation of the Tpr2/Rad9 complex; and (2) the J domain of Tpr2 modulates the
      cellular localization of both Tpr2 itself and Rad9. These results indicate that
      the J domain of Tpr2 plays a critical role in the regulation of both physical and
      functional interactions between Tpr2 and Rad9.

PMID- 11573956
TI  - Basolateral sorting of human poliovirus receptor alpha involves an interaction
      with the mu1B subunit of the clathrin adaptor complex in polarized epithelial
      cells.
AB  - Poliovirus receptor (hPVR/CD155) is a cell surface glycoprotein that belongs to
      the immunoglobulin superfamily but its natural function remains unknown. Two
      membrane-bound isoforms, hPVRalpha and hPVRdelta, are known to date, and they
      differ only in the amino acid sequence of their cytoplasmic domains. To gain an
      insight into the possible function of the cytoplasmic domains, we examined the
      localization of introduced hPVRalpha and hPVRdelta in polarized epithelial cells
      deficient of native hPVRs. Basolateral sorting of hPVRalpha was observed in
      Madine-Darby canine kidney cells expressing mu1B, but not in LLC-PK1 porcine
      kidney cells deficient in mu1B. Distribution of hPVRdelta, however, occurred both
      on the apical and basolateral plasma membranes of these two cell lines.
      Basolateral sorting of hPVRalpha was also seen in LLC-PK1 cells that expressed an
      intact exogenous mu1B, but not in the cells that expressed a mutant mu1B lacking
      binding ability to tyrosine-containing signals. These results indicate that mu1B
      is involved in the distribution of hPVRalpha to the basolateral membrane.
      Comparative distribution analysis of hPVRalpha using a series of mutants with
      truncations and substitutions in the cytoplasmic tail demonstrated that
      determinant for the basolateral sorting resided in the tyrosine-containing motif
      of the cytoplasmic tail. Furthermore, yeast two hybrid analysis strongly
      suggested that the tyrosine motif directly interacted with mu1B protein. Thus,
      basolateral sorting of hPVRalpha appears to involve the interaction with mu1B
      through a tyrosine motif existing in the cytoplasmic domain.

PMID- 11573957
TI  - Embryonic abnormalities from misexpression of cNSCL1.
AB  - cNSCL1 encodes a bHLH transcription factor and is specifically expressed in the
      developing nervous system. We used a replication-competent retrovirus to drive
      misexpression of cNSCL1 in chick embryos. We found that cNSCL1 misexpression was
      embryonic lethal and the embryos exhibited gross abnormalities. Many skeletal
      bones were abnormal and some were completely absent. Expression of BMP4 was
      reduced. The abnormalities were due to cNSCL1 misexpression in the systemic
      region, since microinjection of cNSCL1 retrovirus at one hindlimb primordium
      severely retarded its development, while other limbs on the same animal appeared
      normal. Similar misexpression of cNSCL2, a closely related bHLH gene, did not
      produce these phenotypes. Thus, the detrimental effects on embryonic development
      were specific to cNSCL1. These data indicate that cNSCL1 expression must be
      tightly regulated during development.

PMID- 11573958
TI  - Metabolism of vitamin A affected by prostaglandin F synthase in contractile
      interstitial cells of bovine lung.
AB  - Contractile interstitial cells (CIC), the major component of the alveolar septum
      of the bovine lung are enriched in prostaglandin (PG) F synthase (Fukui, M.,
      Fujimoto, T., Watanabe, K., Endo, K., and Kuno, K. (1996) J. Histochem. Cytochem.
      44, 251-257.). The enzyme catalyzes not only the reduction of PGD(2) and PGH(2)
      but also that of various carbonyl compounds (Watanabe, K., Yoshida, R., Shimizu,
      T., and Hayaishi, O. (1985) J. Biol. Chem. 260, 7035-7041). Here, we report that
      retinal (vitamin A-aldehyde) was reduced to retinol (vitamin A-alcohol) dose- and
      time-dependently by PGF synthase using NADPH as a cofactor. The Km value of PGF
      synthase for retinal was about 20 microM, a same order to that for PGH(2). The
      conversion of retinal to retinol was also observed in cultured CIC, as
      demonstrated by the greenish fluorescence characteristic of retinol. Thus,
      retinal might be one of the natural substrates for PGF synthase in vivo, and
      retinol synthesized from retinal in CIC may play physiological and pathological
      roles in the lungs.

PMID- 11573959
TI  - Diabetes enhances lectin-like oxidized LDL receptor-1 (LOX-1) expression in the
      vascular endothelium: possible role of LOX-1 ligand and AGE.
AB  - Diabetes mellitus accelerating atherosclerosis was associated with the enhanced
      glycoxidative modification of lipoproteins. LOX-1, the endothelial oxidized LDL
      receptor might be involved in the pathogenesis of diabetic atherosclerosis. In
      this study, we examined the vascular expression of LOX-1 in streptozotocin
      induced diabetic rats. We found that LOX-1 was significantly increased in
      diabetic rat aorta compared with nondiabetic control. Immunohistochemistry
      revealed that the most distinctive staining of LOX-1 was in the endothelial
      cells, especially in the bifurcations of artery branches from aorta. In cultured
      aortic endothelial cells, diabetic rat serum and advanced glycation endproducts
      BSA induced LOX-1 expression, while control rat serum along with high glucose did
      not. Applying a competitive inhibition assay, we found that LOX-1 ligand activity
      was accumulated in the diabetic rat serum, mainly in VLDL/LDL fractions. In
      addition, VLDL/LDL prominently increased LOX-1 among all the lipoprotein
      fractions of diabetic rat serum. In conclusion, diabetes markedly upregulated LOX
      1 expression in the aortic endothelial cells. The enhanced glycoxidative
      modification of lipoproteins may contribute to the underlying mechanisms.

PMID- 11573960
TI  - Expression of a functional IL-13Ralpha1 by rat B cells.
AB  - IL-13 mediates its effects through a complex receptor system including IL-4Ralpha
      and a functional IL-13Ralpha1. IL-13 has been reported to have no effects on
      mouse B cells due to a lack of receptor expression. However, on human B cells a
      functional IL-13Ralpha1 has been described. Here, we identified the rat IL
      13Ralpha1 in order to analyze its expression and function in rat B cells. The
      expression of IL-13Ralpha1 has been shown by the presence of mRNA and the
      corresponding protein in purified rat B cells and in rat hybridoma B cell line.
      Rat B cells are able to bind IL-13 and to proliferate when cultured with CD40
      ligand and IL-13. In vivo experiments showed that administration of IL-13 did
      enhance IgE production. These results suggest a direct interaction of rat B cells
      with IL-13 through a functional receptor with an increase of IgE production and
      provide a relevant model to further study the activity of IL-13 and to better
      understand its role in human diseases.

PMID- 11573961
TI  - Truncation of WT1 results in downregulation of cyclin G1 and IGFBP-4 expression.
AB  - Mutations in the WT1 gene are found in a subset of Wilms' tumours and in certain
      other disorders such as Denys-Drash syndrome. The WT1 gene product is a zinc
      finger transcription factor for which many target genes have been suggested. Here
      we utilise gene targeting to generate cells containing only truncated forms of
      WT1, in which the DNA-binding region is disrupted. Examination of gene expression
      in these cells using cDNA macroarrays suggests two novel WT1 transcriptional
      targets, cyclin G1 (Ccng1), and insulin-like growth factor binding protein 4
      (Igfbp4).

PMID- 11573962
TI  - Anti-HIV agent MAP30 modulates the expression profile of viral and cellular genes
      for proliferation and apoptosis in AIDS-related lymphoma cells infected with
      Kaposi's sarcoma-associated virus.
AB  - The anti-HIV agent MAP30 (Momordica anti-HIV protein, 30 kDa) inhibits the
      proliferation of BC-2, an AIDS-related primary effusion lymphoma (PEL) cell line
      derived from an AIDS patient. BC-2 cells are latently infected with Kaposi's
      sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8
      (HHV8). We examined the effect of MAP30 on the expression of viral and cellular
      genes in BC-2 during latent and lytic states of the viral life cycle. By Northern
      analysis and RT-PCR, we found that MAP30 downregulates the expression of viral
      cyclin D (vCD), viral interleukin-6 (vIL-6), and viral FLIP (vFLIP), genes
      involved in cell cycle regulation, viral pathogenesis, and apoptosis. By pathway
      specific cDNA microarray analysis, we found that BC-2 cells express high levels
      of egr-1, ATF-2, hsp27, hsp90, IkappaB, mdm2, skp1, and IL-2, cellular genes
      involved in mitogenesis, tumorigenesis, and inhibition of apoptosis in NFkappaB
      and p53 signaling pathways. These results define for the first time the specific
      cellular pathways involved in AIDS-related tumorigenesis and suggest specific
      novel targets for the treatment. Furthermore, we found that MAP30 downregulates
      the expression of egr-1, ATF-2, hsp27, hsp90, IkappaB, mdm2, and Skp1, while it
      upregulates the pro-apoptotic-related genes Bax, CRADD, and caspase-3. Thus,
      MAP30 modulates the expression of both viral and cellular genes involved in KS
      pathogenesis. These results provide valuable insight into the molecular
      mechanisms of MAP30 anti-KS action and suggest its utility as a therapeutic agent
      against AIDS-related tumors.

PMID- 11573963
TI  - A role for membrane-type serine protease (MT-SP1) in intestinal epithelial
      turnover.
AB  - Membrane type-serine protease 1 (MT-SP1) plays potential roles in the process of
      invasion and metastasis of carcinomas. In the present study, we cloned a rat MT
      SP1 cDNA and investigated the intestinal distribution and proteolytic properties
      of the enzyme. By in situ hybridization we found the prominent expression of the
      mRNA in the epithelial layer of the small intestinal upper villi and of the
      colon, where cells are loosely attached to the basement membrane. When MT-SP1 was
      expressed in Caco-2, a colonic carcinoma cell line, the protein was localized
      exclusively on the basolateral side. A secreted form of the enzyme produced in
      COS-1 cells digested fibronectin and laminin. These findings suggest that MT-SP1
      participates in the control of intestinal epithelial turnover by regulating the
      cell-substratum adhesion.

PMID- 11573964
TI  - Ets-2 is induced by oxidative stress and sensitizes cells to H(2)O(2)-induced
      apoptosis: implications for Down's syndrome.
AB  - An elevated production of hydrogen peroxide mediates the increased rate of
      apoptosis of cells derived from individuals with Down's syndrome. The mechanism
      via which this occurs is unknown. Here we show that Ets-2, a transcription factor
      located on human chromosome 21 and already overexpressed in multiple tissues in
      Down syndrome (DS, trisomy 21), is induced by low concentrations of hydrogen
      peroxide. Moreover, cells with an imbalance in the antioxidant enzymes SOD-1/GPX
      1, such as occurs in DS through the overexpression of the chromosome 21 gene SOD
      1, also results in increased Ets-2 expression. The increase in Ets-2 expression
      is dependent on mRNA transcription. Importantly, we further demonstrate that 3T3
      fibroblasts that overexpress Ets-2 are sensitized to hydrogen peroxide-induced
      apoptosis. These data implicate Ets-2 in the regulation of oxidant-induced
      apoptosis and provide a possible rationale for both the (5- to 7-) fold increase
      in Ets-2 protein level in DS tissues, above the expected gene dosage of 1.5-fold,
      and the elevated rate of apoptosis in DS cells.

PMID- 11573965
TI  - Oxidant-dependent phosphorylation of p40phox in B lymphocytes.
AB  - As with the neutrophil NADPH oxidase, the B lymphocyte NADPH oxidase consists of
      a membrane-bound flavocytochrome b and regulatory factors including Rac and the
      cytosolic phox protein triad p67phox, p47phox, and p40phox. Here we demonstrate
      by phosphoamino acid analysis and the use of the potent PKC inhibitor GFX that,
      in response to stimulation of B lymphocytes with sodium orthovanadate and
      H(2)O(2), the p40phox component of the cytosolic phox triad is selectively
      phosphorylated on serine and threonine residues by a PKC-type protein kinase. The
      pattern of p40phox phosphorylation was closely related to the kinetics of
      tyrosine phosphorylation of PKC-delta, the main PKC isotype of B lymphocytes.
      Blocking H(2)O(2)-dependent tyrosine phosphorylation of PKC by genistein resulted
      in inhibition of p40phox phosphorylation. The correlation between the tyrosine
      phosphorylation of PKC-delta and the serine/threonine phosphorylation of p40phox,
      together with the inhibition of p40phox phosphorylation by rottlerin, a selective
      inhibitor of PKC-delta, makes the activated PKC-delta a likely candidate in the
      process of the oxidant-dependent phosphorylation of p40phox in B cells.

PMID- 11573966
TI  - Rapid activation of ERK1/2 mitogen-activated protein kinase by corticosterone in
      PC12 cells.
AB  - Although the nongenomic effects of glucocorticoids have been well acknowledged,
      its precise intracellular signal transduction pathway remains to be elucidated.
      The present study using Western immunoblot and protein kinase activity assay, for
      the first time, showed that corticosterone (B) can induce a rapid activation of
      Erk1/2 mitogen-activated protein kinase (MAPK) in PC12 cells. The dose-response
      curve was bell shaped, with the maximal activation at 10(-9) M in 15 min. The
      results from immunofluorescence staining also revealed that the activated Erk1/2
      MAPK was translocated from cytoplasm to nucleus of PC12 cells in 15 min.
      Activation of Erk1/2 MAPK by B was apparently not mediated by the classical
      cytosolic steroid receptors, for B-BSA can induce the phosphorylation of Erk1/2
      MAPK, but the antagonist (RU38486) cannot block the phosphorylation of Erk1/2
      MAPK induced by B. Phosphorylation of Erk1/2 MAPK induced by B was not affected
      by a tyrosine kinase inhibitor (genistein), suggesting that the pathway did not
      involve the tyrosine kinase activity. On the other hand, protein kinase C
      activator (PMA) can activate and protein kinase C inhibitor (Go6976) can block
      the activation of Erk1/2 MAPK induced by B. Taken together, these data clearly
      demonstrated that B might act via putative membrane receptor and rapidly activate
      Erk1/2 MAPK through protein kinase C alpha in PC12 cells.

PMID- 11573967
TI  - Inducible RGS2 is a cross-talk regulator for parathyroid hormone signaling in rat
      osteoblast-like UMR106 cells.
AB  - Parathyroid hormone (PTH) activates dual signal transduction systems via Galphas
      and Galphaq proteins. We now report a novel mechanism by which "cross-talk" may
      occur between the Galphas and Galphaq signaling pathways. RGS2 (Regulator of G
      protein Signaling 2) mRNA was rapidly and transiently increased only by PTH
      analogs (PTH1-84, 1-34, 1-31, and PTHrP) that activated the Galphas-mediated
      cAMP/PKA signaling pathway, whereas activation of the Galphaq-mediated Ca(2+)/PKC
      signaling pathway by PTH3-34 had no effect on RGS2 expression. Treatment of
      UMR106 cells with nonPTH activators of the cAMP/PKA signaling pathway such as
      cholera toxin, forskolin, 8-Br-cAMP, and dibutyryl-cAMP also significantly
      elevated RGS2 mRNA levels, while activator of the Galphaq pathway PMA did not.
      Pretreatment using the Galphas signaling pathway inhibitors SQ22536 and H89
      significantly blocked PTH-induced RGS2 expression, but the Galphaq signaling
      pathway inhibitor bisindolylmaleimide I had no effect. Therefore, RGS2 expression
      is governed solely by the Galphas signaling pathway. Additionally, we demonstrate
      for the first time that RGS2 binds to both Galphas and Galphaq subunits in their
      transition state (GDP/AlF(-4)-bound) forms, suggesting that RGS2 has the
      potential to act as a bridge between the cAMP/PKA and Ca(2+)/PKC pathways, and
      that it may act as a cross-talk regulator for these two PTH signaling pathways.

PMID- 11573971
TI  - Vasopressin gene expression: experimental models and strategies.
AB  - The intergenic region (IGR) separating the genes for vasopressin (VP) and
      oxytocin (OT) has been shown to be critical for the cell-specific expression of
      these peptide genes in hypothalamic neurons. To date, the most relevant
      information about the putative cis-elements in the IGR that might determine cell
      specific gene expression has come from studies in transgenic models. As a first
      step toward increasing the efficiency of the IGR sequence deletion studies in
      transgenic animals, a comparative genomics approach comparing the IGR sequence in
      humans versus mice was used to identify conserved sequences that might be
      candidate regulatory elements. The nucleotide sequence of the IGR between the
      human VP and OT genes was determined and compared to the mouse IGR, and 26
      conserved sequences in three distinct clusters were found. These conserved
      sequences and motifs may be important for the cell-specific expression of the VP
      and OT genes. However, before further significant progress can be made, a "high
      throughput" method for the analysis of deletion constructs in relevant cell types
      in vitro is needed. It is proposed here that organotypic culture models combined
      with the use of particle-mediated gene transfer methods may provide an effective,
      general strategy for the study of cell-specific expression in the central nervous
      system.

PMID- 11573968
TI  - Retrovirus-mediated gene therapy for hepatocellular carcinoma with reversely
      oriented therapeutic gene expression regulated by alpha-fetoprotein
      enhancer/promoter.
AB  - In the present study, to achieve more selective and efficient therapeutic gene
      expression in hepatoma cells, we compared the therapeutic efficacies of the
      retroviral vectors expressing the herpes simplex virus thymidine kinase (HSV-tk)
      gene by the alpha-fetoprotein (AFP) enhancer/promoter in the forward (LNAFE0.3TK)
      and reverse (LN[AFE0.3TK]R) orientation to the vector long terminal repeats. By
      Northern blotting, the level of the HSV-tk mRNA in LN[AFE0.3TK]R-infected HepG2
      human hepatoma cells was much higher than that in LNAFE0.3TK-infected cells.
      Consistent with this, LN[AFE0.3TK]R infection into HepG2 cells caused a greater
      cytotoxicity by ganciclovir exposure together with a stronger bystander effect
      than LNAFE0.3TK infection. In an animal model, intratumorous injection of
      LN[AFE0.3TK]R with ganciclovir treatment resulted in pronounced growth inhibition
      of HepG2 tumor. Thus, the reversely oriented therapeutic gene expression under
      the control of AFP enhancer/promoter is a possible candidate for the retrovirus
      mediated gene therapy for hepatocellular carcinoma.

PMID- 11573972
TI  - Neurotransmitter/neuropeptide interactions in the regulation of neurohypophyseal
      hormone release.
AB  - Regulation of neurohypophyseal hormone release reflects the convergence of a
      large number of afferent pathways on the vasopressin (VP)- and oxytocin-producing
      neurons. These pathways utilize a broad range of neurotransmitters and
      neuropeptides. In this review, the mechanisms by which this information is
      coordinated into appropriate physiological responses is discussed with a focus on
      the responses to agents that are coreleased from A1 catecholamine nerve terminals
      in the supraoptic nucleus. The A1 pathway transmits hemodynamic information to
      the vasopressin neurons by releasing several neuroactive agents including ATP,
      norepinephrine, neuropeptide Y, and substance P. These substances stimulate VP
      release from explants of the hypothalamo-neurohypophyseal system and certain
      combinations of these agents elicit potent but selective synergism. Evaluation of
      the signal cascades elicited by these agents provides insights into mechanisms
      underlying these synergistic interactions and suggests mechanisms responsible for
      coordinated responses of the VP neurons to activation of a range of ion-gated ion
      channel and G-protein-coupled receptors.

PMID- 11573973
TI  - Peptidergic excitation of supraoptic nucleus neurons: involvement of stretch
      inactivated cation channels.
AB  - Although the primary stimulus regulating vasopressin (VP) release is a change in
      systemic osmolality, other physiological parameters are known to affect VP
      secretion or modulate the osmotic control over its release. Neuropeptides feature
      prominently in afferents underlying the central regulation of the VP-releasing
      magnocellular neurosecretory cells (MNCs). Although little is yet known of the
      circumstances under which peptides are released onto MNCs, previous studies have
      shown that a common response profile to exogenous peptide application is a slow
      excitation that seems to result from the activation of a nonselective cation
      conductance. In this paper we review the basis for the excitatory effects of
      angiotensin II, cholecystokinin, and neurotensin in MNCs acutely isolated from
      the supraoptic nucleus of adult rats. Saturating concentrations of these three
      peptides evoked nonadditive increases in macroscopic cation conductance. During
      single-channel recordings Ang II, CCK, and NT caused kinetically identical
      increases in the probability of opening of 35-pS nonselective cation channels.
      Patches containing only one channel further revealed that the activity of single
      channels could be regulated by separate applications of all three peptides.
      Peptide-stimulated channels were also found to be inactivated by increases in
      membrane stretch and to be blocked by low concentrations of gadolinium (Gd(3+)).
      It is concluded that many excitatory peptides depolarize MNCs by stimulating the
      stretch-inactivated cation channels underlying osmoreception. Convergent
      regulation of these channels provides a potentially powerful mechanism for
      integrating signals derived from the various afferents involved in the regulation
      of MNCs.

PMID- 11573974
TI  - Cardiovascular regulation of vasopressin neurons in the supraoptic nucleus.
AB  - This paper reviews the regulation of hypothalamic vasopressin and oxytocin
      neurosecretory cells in the neural response to plasma volume expansion. Many
      questions remain unanswered regarding how an increase in volume affects
      neurohypophysial hormone secretion, what receptors are important in mediating
      this response, and which neural pathways are responsible for conveying the signal
      from those receptors to the hypothalamus. Plasma volume expansion activates
      regions of the central nervous system associated with inhibition of vasopressin
      release, oxytocin secretion, and inhibition of sympathetic nerve activity.
      Cardiac receptors, not arterial baroreceptors, are primarily responsible for
      activation of the regions associated with regulation of vasopressin secretion and
      sympathetic outflow. Other stimuli that as yet are undefined account for
      activation of oxytocin-secreting neurons. Electrophysiology experiments have
      measured the inhibition of vasopressin-secreting magnocellular neurons in the
      supraoptic nucleus by select stimulation of cardiac receptors in the caval-atrial
      junction. Further experiments suggest that the perinuclear zone, a population of
      neurons surrounding the supraoptic nucleus, is a necessary part of the pathway by
      which caval-atrial stretch decreases the excitability of vasopressin neurons. The
      perinuclear zone is also a necessary synapse for arterial baroreceptor-mediated
      inhibition of vasopressin neurons. This suggests that the neural pathways that
      inhibit vasopressin release in response to an increase in blood pressure and an
      increase in blood volume may overlap at the perinuclear zone of the supraoptic
      nucleus. Finally, the integration of various neural pathways activated by
      multiple receptors to ultimately determine the activity of magnocellular neurons
      and vasopressin secretion is discussed.

PMID- 11573975
TI  - Regulation of the abundance of renal sodium transporters and channels by
      vasopressin.
AB  - Vasopressin plays a role in both salt and water balance in the kidney. Classic
      studies, utilizing isolated perfused tubules, have revealed that vasopressin
      increases sodium reabsorption in the kidney thick ascending limb and the
      collecting duct. Furthermore, the activity of several sodium transport proteins
      expressed in these segments, such as the bumetanide-sensitive Na-K-2Cl
      cotransporter (NKCC2) and the epithelial sodium channel (ENaC), have been shown
      to be directly increased by vasopressin. Increased protein abundance might be one
      means through which sodium transporter and channel activity is enhanced. We have
      used immunoblotting and immunohistochemistry in order to investigate the
      regulation of abundance of the major sodium transporters and channels expressed
      along the renal tubule in response to vasopressin. Chronic (7-day) studies were
      performed in which vasopressin levels were elevated either endogenously by water
      restriction of Sprague-Dawley rats or exogenously through infusion of the
      vasopressin V2-receptor-selective agonist, dDAVP (1-deamino-8d-arginine
      vasopressin), to Brattleboro rats. We found a significant increase in protein
      abundance for NKCC2 and the beta- and gamma-subunits of ENaC with either water
      restriction or dDAVP infusion. The alpha-subunit of Na-K-ATPase was increased by
      water restriction, but not by dDAVP infusion, and alpha-ENaC and the thiazide
      sensitive cotransporter (NCC) were increased by dDAVP infusion but not by water
      restriction. Acute (60-min) in vivo exposure to dDAVP led to an increase in both
      beta- and gamma-ENaC abundance in kidney cortex homogenates, displaying the rapid
      nature of some of these changes. Overall these increases in sodium transporter
      and channel abundances likely contribute to both the antidiuretic and
      antinatriuretic actions of vasopressin.

PMID- 11573976
TI  - Localization of agmatine in vasopressin and oxytocin neurons of the rat
      hypothalamic paraventricular and supraoptic nuclei.
AB  - Agmatine (decarboxylated l-arginine), an endogenous ligand of imidazoline and
      alpha(2) adrenoreceptors, is particularly enriched in the rat hypothalamic
      paraventricular (PVN) and supraoptic (SON) nuclei. The present study utilized
      light and electron microscopic immunocytochemical methods to determine the
      distribution and extent of colocalization of agmatine relative to subpopulations
      of vasopressin- (VP) and oxytocin- (OT) producing neurons in PVN and SON nuclei.
      By light microscopy, agmatine-immunoreactive perikarya were found in both the
      magnocellular and the parvocellular neuronal subdivisions of PVN and SON.
      Confocal and electron microscopy revealed that agmatine-immunoreactivity (I)
      within neuronal perikarya was associated with the nuclear membrane as well as
      mitochondria, Golgi complexes, endoplasmic reticula, and plasmalemma.
      Additionally, agmatine-I was identified in both axons and axonal terminals, which
      were enriched in large dense-core vesicles. Dual and triple immunocytochemical
      labeling experiments also demonstrated that agmatine coexists with VP or OT in
      most PVN and SON magnocellular neurons. Combinations of iontophoretic injections
      of Fluorogold into the dorsomedullary complex with immunocytochemical labeling
      revealed that many retrogradely labeled neurons in the parvocellular region of
      the PVN contained agmatine-I and either VP or OT. These findings provide evidence
      that agmatine may function as a modulator of both hypothalamically mediated
      neuroendocrine and autonomic responses.

PMID- 11573977
TI  - Effect of forskolin and exogenously administered oxytocin mRNA on oxytocin
      release by dispersed hypothalamic cultures.
AB  - Differential vasopressin (VP) gene expression and oxytocin (OT) gene expression
      were observed in hypothalamic cultures derived from 14-day-old rat fetuses, with
      VP but not OT being induced by treatment with forskolin and 3-isobutyl-1
      methylxanthine. These cultures were used to demonstrate that exogenous VP mRNA
      could be taken up and translated into releasable VP. In the current studies a
      similar culture preparation was used to test the hypothesis that, due to the
      similarity in the mRNA and prohormone structures of VP and OT, the VP-expressing
      neurons in the cultures would be capable of utilizing exogenous OT mRNA for
      synthesis of releasable OT. Although OT release was increased by the
      administration of exogenous OT mRNA, endogenous OT gene expression was also
      observed. To determine what had induced OT gene expression in the current
      cultures, the undefined components of the culture preparation, e.g., the glial
      feeder layer and the serum component of the culture medium, were evaluated.
      Restraining growth of the glial carpet with cytosine-arabinoside did not alter OT
      gene expression. Use of a defined medium supplemented with B-27 induced optimal
      OT gene expression. From this, it is possible to conclude that the components
      included in B-27 are sufficient for OT gene expression.Factors included in
      earlier lots of sera may have been responsible for suppression of OT gene
      expression. Cultures maintained in serum-free, B-27-supplemented medium may
      provide a useful model system for studying OT gene regulation.

PMID- 11573978
TI  - Cell-specific expression and subcellular localization of neurophysin-CAT-fusion
      proteins expressed from oxytocin and vasopressin gene promoter-driven constructs
      in transgenic mice.
AB  - The cell-specific expression of both the oxytocin (OT) and vasopressin (VP) genes
      in magnocellular neurons (MCNs) of the hypothalamus has been proposed to be under
      the control of cis-elements in an intergenic region downstream of the VP gene. We
      examined this hypothesis using transgenic mice containing mouse genomic DNA
      derived constructs linked to chloramphenicol acetyltransferase (CAT) reporters.
      VP gene expression was studied using constructs containing 3.8 kbp of the 5'
      flanking region and all the exons and introns in the mouse VP gene, which was
      fused at the end of exon 3 to a CAT reporter. The two VP-transgene constructs
      differed by the lengths of their VP gene 3' flanking regions (2.1 versus 3.6
      kbp). A similar construct for the oxytocin CAT transgene was used which contained
      the full-length (3.6 kbp) downstream intergenic region between the mouse genes.
      All three transgenic constructs produced cell-specific expression of the CAT
      reporter in the magnocellular neurons as determined by CAT-immunoreactivity.
      Oxytocin transgene expression was restricted to OT cells in two founders, and the
      two VP transgenes to VP cells in five founders. Electron microscopic
      immunocytochemistry showed that the CAT fusion proteins produced from the OT- and
      VP-transgenes were efficiently trafficked through the regulated secretory
      pathways in their respective magnocellular neurons, packaged into large dense
      core vesicles, and transported to nerve terminals in the posterior pituitary.

PMID- 11573979
TI  - Divergent effects of ovarian steroids on neuronal survival during experimental
      allergic encephalitis in Lewis rats.
AB  - Experimental allergic encephalitis, (EAE) a Th1-cell-dependent autoimmune disease
      of the central nervous system (CNS) used to study immune responses relevant to
      multiple sclerosis (MS) displays gender susceptibility. The underlying basis of
      the sexual dimorphism may reflect multiple factors including gender-specific
      hormones. To study the relationship between ovarian hormones and CNS
      inflammation, we induced EAE in susceptible female Lewis rats ovariectomized
      (OVX) 7 days earlier and implanted with blank capsules or capsules containing
      estradiol (E), progesterone (P), or both (EP). Rats were immunized with complete
      Freunds' adjuvant alone or combined with guinea pig myelin basic protein. Motor
      function was scored 0-5 on standard criteria (days 7-11 postimmunization). On day
      11, the rats were euthanized and the lumbar spinal cord was analyzed for Nissl,
      neuron nuclear antigen, and DNA fragmentation with a TUNEL assay. Inflammation
      was judged qualitatively on a scale of 0-4. Our immunization protocol induced
      limited sensorimotor deficits in OVX rats (2.3 +/- 0.6, mean +/- SEM) with
      moderate inflammation (2.5 +/- 0.4). E limited both behavioral impairments (1.0
      +/- 0.4) and inflammation (0.5 +/- 0.2). P-treated rats had more severe
      sensorimotor deficits (3.1 +/- 0.5) with increased inflammatory infiltrates (3.6
      +/- 0.4) and markedly increased numbers of TUNEL(+) neurons. Neuron counts of the
      outer two Rexed lamina (L3-L5) showed a 20% neuron loss (P < 0.02) in P-treated
      rats with EAE in comparison to other groups. Coadministration of E with P
      prevented the consequences of P, including neuronal apoptosis (behavioral score,
      0.6 +/- 0.6; inflammation, 1.4 +/- 0.5). Our results suggest a potential and
      novel function of P that increases the vulnerability of neurons to apoptotic
      injury in EAE and may have pathophysiologic implications in the progression of
      disability in women with MS.

PMID- 11573980
TI  - Serotonin modulates expression of VIP and GRP mRNA via the 5-HT(1B) receptor in
      the suprachiasmatic nucleus of the rat.
AB  - The expression of vasoactive intestinal peptide (VIP) and gastrin-releasing
      peptide (GRP) in the suprachiasmatic nucleus (SCN) changes depending on light.
      VIP mRNA increases and GRP mRNA decreases in the light phase, while they do not
      show change without light. In the present study we investigated the involvement
      of serotonin (5-HT) in the expression of VIP and GRP messenger RNA in the SCN of
      the rat. The decrease in VIP mRNA and the increase in GRP mRNA in the light phase
      were amplified by 5-HT depletion using 5,6-dihydroxytryptamine injected into the
      lateral ventricle. These enhancements due to 5-HT depletion were reversed to
      control levels by applying 5-HT(1B) agonists TFMPP and CGS12066A, but not a 5
      HT(1A)/5-HT(7) agonist, 8-OH-DPAT. The 5-HT(1B) receptor is known to exist on the
      terminals of the retinohypothalamic tract (RHT). Therefore, next we investigated
      the morphological relationship of RHT and 5-HT terminals by double-labeling
      immunocytochemistry and demonstrated that 5-HT-immunoreactive fibers and cholera
      toxin B subunit-labeled RHT terminals were intermingled in the ventrolateral SCN,
      and 5-HT axon processes had close contact with RHT terminals. Collectively, these
      pharmacological and morphological results suggest that 5-HT afferents from raphe
      nuclei modulate VIP and GRP expression in neurons of the ventrolateral SCN by
      activating the 5-HT(1B) receptor in the RHT.

PMID- 11573982
TI  - Estrogen decreases the responsiveness of subfornical organ neurons to
      angiotensinergic neural inputs from the lateral hypothalamic area in the female
      rat.
AB  - Twenty-eight subfornical organ (SFO) neurons in ovariectomized (OVX) female rats
      that were treated with propylene glycol (PG) vehicle and 26 SFO neurons in OVX
      female rats that were treated with estrogen benzoate (EB) were antidromically
      activated by electrical stimulation of the hypothalamic paraventricular nucleus
      (PVN) under urethane anesthesia. No significant differences were observed between
      the PG-treated and EB-treated OVX animals in the latency, conduction velocity, or
      threshold of antidromic activation. The mean spontaneous discharge rate was
      significantly lower in the EB-treated than in the PG-treated OVX animals. In both
      groups, the activity of the majority (86% in the PG-treated animals and 88% in
      the EB-treated animals) of identified SFO neurons were activated by
      microiontophoretic application of angiotensin II (ANG II). Electrical stimulation
      of the lateral hypothalamic area (LHA) increased the excitability of these ANG II
      sensitive SFO neurons (58% in the PG-treated animals and 52% in the EB-treated
      animals). The excitatory response to either ANG II or LHA stimulation was blocked
      by microiontophoretic application of the ANG II antagonist saralasin (Sar),
      suggesting that the excitatory response to LHA stimulation may be mediated by
      angiotensinergic LHA projections to the SFO. The magnitude of excitatory response
      to either ANG II or the LHA stimulation was much greater in the PG-treated than
      in the EB-treated animals. These results suggest that estrogen decreases the
      responsiveness of SFO neurons projecting to the PVN to angiotensinergic inputs
      from the LHA.

PMID- 11573981
TI  - Carbon monoxide and nitric oxide: interacting messengers in muscarinic signaling
      to the brain's circadian clock.
AB  - Within the central nervous system, acetylcholine (ACh) functions as a state
      dependent modulator at a range of sites, but its signaling mechanisms are yet
      unclear. Cholinergic projections from the brain stem and basal forebrain
      innervate the suprachiasmatic nucleus (SCN), the master circadian clock in
      mammals, and cholinergic stimuli adjust clock timing. Cholinergic effects on
      clock state require muscarinic receptor-mediated activation of guanylyl cyclase
      and cGMP synthesis, although the effect is indirect. Here we evaluate the roles
      of carbon monoxide (CO) and nitric oxide (NO), major activators of cGMP
      synthesis. Both heme oxygenase 2 (HO-2) and neuronal nitric oxide synthase
      (nNOS), enzymes that synthesize CO and NO, respectively, are expressed in rat
      SCN, with HO-2 localized to the central core of the SCN, whereas nNOS is a
      punctate plexus. Hemin, an activator of HO-2, but not the NO donor, SNAP,
      mimicked cholinergic effects on circadian timing. Selective inhibitors of HO
      fully blocked cholinergic clock resetting, whereas NOS inhibition partially
      attenuated this effect. Hemoglobin, an extracellular scavenger of both NO and CO,
      blocked cholinergic stimulation of cGMP synthesis, whereas l-NAME, a specific
      inhibitor of NOS, had no effect on cholinergic stimulation of cGMP, but decreased
      the cGMP basal level. We conclude that basal NO production generates cGMP tone
      that primes the clock for cholinergic signaling, whereas HO/CO transmit
      muscarinic receptor activation to the cGMP-signaling pathway that modulates clock
      state. In light of the recently reported inhibitory interaction between HO-2/CO
      and amyloid-beta, a marker of Alzheimer's disease (AD), we speculate that HO-2/CO
      signaling may be a defective component of cholinergic neurotransmission in the
      pathophysiology of AD, whose manifestations include disintegration of circadian
      timing.

PMID- 11573983
TI  - Estrogen effects on neurite outgrowth and cytoskeletal gene expression in ERalpha
      transfected PC12 cell lines.
AB  - The potential of gonadal steroids like estrogen (E) to promote neurite sprouting
      is of interest in development and aging, as well as after neural trauma. The
      specific roles of the two main estrogen receptors, ERalpha and ERbeta, in
      neuronal sprouting are not yet well understood. We examined the hypothesis that E
      can enhance nerve growth factor (NGF)-stimulated neurite sprouting in an ERalpha
      dependent manner. PC12 cells that were stably transfected with the full-length
      rat ERalpha gene (PCER) and a control line of cells transfected with vector DNA
      alone (PCCON) were compared. Both cell lines vigorously differentiate neurites
      when treated with NGF. We determined that both lines show basal expression of
      ERbeta mRNA, but only the PCER cells express ERalpha mRNA. Estrogen treatment
      markedly enhanced NGF-stimulated neurite outgrowth from PCER but not from PCCON
      cells. Significantly larger proportions of PCER cells (34 and 53% at 24 and 48 h,
      respectively) had neurites than did the PCCON cells (17 and 26% at 24 and 48 h)
      after E plus NGF treatment. We also examined the effects of E and NGF treatment
      of PCER and PCCON cells on peripherin, alpha-tubulin, and tau mRNA expression. In
      undifferentiated PCER cells, E treatment increased peripherin, reduced alpha
      tubulin, and did not alter tau mRNA levels. No changes in these mRNAs were
      observed in the controls (undifferentiated PCCON cells) after E treatment. NGF
      treatment markedly stimulated expression of peripherin, alpha-tubulin, and tau
      mRNAs in both PCER and PCCON cells. From these observations we conclude that E
      synergizes with NGF and stimulates neurite sprouting and also modulates
      expression of several cytoskeletal mRNAs through ERalpha.

PMID- 11573984
TI  - Histaminergic control of oxytocin release in the paraventricular nucleus during
      lactation in rats.
AB  - The central neurotransmitters regulating both systemic and central release of
      oxytocin (OT) during lactation are not completely defined. Although central
      histaminergic systems have been implicated in systemic release of OT, the role of
      this neurotransmitter in suckling-induced intranuclear OT secretion has not been
      investigated. Therefore, microdialysis of the paraventricular nucleus (PVN) was
      used to determine if suckling stimulates histamine release within the PVN and if
      nursing-induced intranuclear OT release is reduced by local blockade of either H1
      or H2 histamine receptors. Female Holtzman rats were implanted with microdialysis
      probes adjacent to the PVN on lactation days 8-12. The next day, the pups and dam
      were separated for 4 h, reunited, and again separated. Histamine concentrations
      in dialysates were measured before, during, and following suckling. In separate
      animals, a similar separation/reunion paradigm was used, but the dialysate OT
      concentration was measured during PVN perfusion with vehicle or an H1 or H2
      receptor antagonist. Suckling increased dialysate concentrations of both
      histamine and OT in the PVN. Furthermore, local pharmacological blockade of
      either H1 or H2 receptors prevented the increase in OT release in the PVN during
      suckling. These data demonstrate that activation of histamine receptors in the
      PVN is necessary for intranuclear release of OT induced by suckling and extend
      previous findings demonstrating a similar relationship between central histamine
      and systemic release of OT.

PMID- 11573985
TI  - Enhanced salt intake in oxytocin deficient mice.
AB  - The maternal roles of oxytocin (OT) are well known, but recent work suggests that
      OT is also a vital component in fluid balance regulation. To explore the role of
      OT in salt/volume regulation, we studied NaCl intake in a genetically modified
      mouse strain lacking OT. Using male control and OT knockout mice (OTKO), we
      determined the circadian pattern of salt and water intake under need-free
      conditions. For the study of intake, a two-bottle choice system was used to
      provide access to water and 2% NaCl with computerized monitoring of licking
      activity. Salt licking activity (licks/24 h) for controls was 59 +/- 22 vs. 380
      +/- 105 in OTKO (P < 0.05). The volume of salt consumed (ml/24 h) was 0.4 +/- 0.1
      in controls vs. 1.8 +/- 0.4 in OTKO (P < 0.01). There was no statistical
      difference in the consumption of water between the groups. However, the
      initiation of water intake was shifted, with an advancement of almost 3 h in OTKO
      (P < 0.01). Differences in the timing of salt intake could not be determined due
      to the low volume of salt consumed by controls. Taken together, these data show
      that removal of OT amplifies the salt-seeking behavior associated with normal
      daily fluid fluctuations. The fact that OTKO voluntarily consume a normally
      aversive salt solution further implies that OT is a powerful regulator of
      circadian salt appetite.

PMID- 11573986
TI  - Hypothalamic pituitary adrenal axis and hypothalamic-neurohypophyseal
      responsiveness in water-deprived rats.
AB  - The differential effects of osmotic stimulation on magnocellular and
      parvocellular hypothalamic neurons were studied by analysis of corticotropin
      releasing hormone (CRH) and vasopressin (VP) expression in controls and 48-h
      water-deprived rats subjected to either restraint for 1 h or a single
      lipopolysaccharide injection (250 microg/100 g). Water deprivation reduced basal
      CRH mRNA levels but the increments following 4 h of restraint or 6 h
      lipopolysaccharide (LPS) injection were similar to those in controls. In
      contrast, water deprivation had no effect on basal VP heteronuclear RNA (hnRNA)
      and mRNA levels in parvocellular neurons, but responses to restraint or LPS
      injection were reduced. VP expression in magnocellular paraventricular and
      supraoptic nuclei, and plasma sodium and vasopressin were higher in water
      deprived rats, changes which were unaffected by restraint. LPS injection reduced
      VP mRNA but not hnRNA levels in magnocellular neurons and increased plasma
      vasopressin levels only in water-deprived rats independently of changes in plasma
      sodium. This was accompanied by an increase in vasopressin mRNA content in the
      posterior pituitary. The data show that the blunted ACTH responses to acute
      stress during chronic osmotic stimulation are correlated with the inability of
      parvocellular neurons to increase VP rather than CRH expression. In addition, LPS
      induced endotoxemia causes disturbances of the magnocellular vasopressinergic
      system with an unexpected potentiation of osmotic simulated VP secretion. The
      lack of increase in VP transcription after LPS and changes in VP mRNA
      distribution suggest that endotoxemia affect the secretory process at the levels
      of the neurohypophyseal axon terminal.

PMID- 11573987
TI  - Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers
      and multiple end-plate formation.
AB  - This study examined the role of glial cell line-derived neurotrophic factor
      (GDNF) in synaptic plasticity at the developing neuromuscular junction.
      Transgenic mice overexpressing GDNF in skeletal muscle under the myosin light
      chain-1 promoter were isolated. Northern blot and ELISA at 6 weeks of age
      indicated that GDNF mRNA and protein levels were elevated threefold in the
      lateral gastrocnemius muscle (LGM) of the GDNF-transgenic animals. Histochemical
      examination of LGM tissue sections at 6 weeks of age revealed a 70% increase in
      the number of cholinesterase-positive end plates without changes in end-plate
      area. Multiple end plates on a single muscle fiber were also observed, in
      addition to multiple axonal processes terminating on individual end plates. No
      change in the number of spinal motoneurons, overall LGM size, or muscle type
      composition was observed. Finally, overexpression of GDNF in muscle caused
      hypertrophy of neuronal somata in dorsal root ganglia without affecting their
      number. These findings demonstrate that overexpression of a single neurotrophic
      factor in skeletal muscle induces multiple end-plate formation and maintains
      hyperinnervation well beyond the normal developmental period. We suggest that
      GDNF, a muscle-derived motoneuron neurotrophic factor, serves an important role
      in the regulation of synaptic plasticity in the developing and adult
      neuromuscular junction.

PMID- 11573988
TI  - A bile acid protects against motor and cognitive deficits and reduces striatal
      degeneration in the 3-nitropropionic acid model of Huntington's disease.
AB  - There is currently no effective treatment for Huntington's disease (HD), a
      progressive, fatal, neurodegenerative disorder characterized by motor and
      cognitive deterioration. It is well established that HD is associated with
      perturbation of mitochondrial energy metabolism. Tauroursodeoxycholic acid
      (TUDCA), a naturally occurring bile acid, can stabilize the mitochondrial
      membrane, inhibit the mitochondrial permeability transition, decrease free
      radical formation, and derail apoptotic pathways. Here we report that TUDCA
      significantly reduced 3-nitropropionic acid (3-NP)-mediated striatal neuronal
      cell death in cell culture. In addition, rats treated with TUDCA exhibited an 80%
      reduction in apoptosis and in lesion volumes associated with 3-NP administration.
      Moreover, rats which received a combination of TUDCA + 3-NP exhibited
      sensorimotor and cognitive task performance that was indistinguishable from that
      of controls, and this effect persisted at least 6 months. Bile acids have
      traditionally been used as therapeutic agents for certain liver diseases. This is
      the first demonstration, however, that a bile acid can be delivered to the brain
      and function as a neuroprotectant and thus may offer potential therapeutic
      benefit in the treatment of certain neurodegenerative diseases.

PMID- 11573989
TI  - Engraftment of serotonergic precursors enhances locomotor function and attenuates
      chronic central pain behavior following spinal hemisection injury in the rat.
AB  - Spinal cord injury (SCI) results in abnormal locomotor and pain syndromes in
      humans. T13 spinal hemisection in the rat results in development of permanent
      mechanical allodynia and thermal hyperalgesia partially due to interruption of
      descending inhibitory modulators such as serotonin (5-HT). We hypothesize that
      lumbar transplantation of nonmitotic cells that tonically secrete antinociceptive
      and trophic compounds will reduce the pain-like behavior and enhance locomotor
      recovery after SCI. We used RN46A-B14 cells, a conditionally immortalized
      (SV40tsTag) rat neuronal cell line derived from E13 raphe bioengineered to
      secrete both 5-HT and BDNF in vitro at both permissive (33 degrees C) and
      nonpermissive (39 degrees C) temperatures. Three groups (n = 72) of 30-day-old
      male Sprague-Dawley rats were spinally hemisected at T13 and allowed 4 weeks for
      adequate recovery of locomotor function and development of allodynia and
      hyperalgesia. Immunosuppressed animals received either lumbar RN46A-B14 (n = 24)
      or control RN46A-V1 (n = 24) empty-vector transplants or no cell (n = 24)
      transplant. HPLC analysis of media and CSF demonstrated increases of both in
      vitro and in vivo 5-HT levels at 28 days in RN46A-B14 animals. ELISA demonstrated
      BDNF secretion in vitro and in vivo by RNA46A-B14 cells. Locomotor function (BBB
      scale) and nociceptive behaviors measured by paw withdrawals to von Frey
      filaments, radiant heat, and noxious pin stimuli were tested for 4 weeks
      posttransplant. Animals receiving RN46A-B14 cells demonstrated significantly
      improved locomotor function and reductions in both fore- and hindlimb mechanical
      allodynia and thermal hyperalgesia compared to controls receiving RN46A-V1 or no
      transplants. These effects were modulated by the 5-HT antagonist methysergide and
      reuptake inhibitor fluvoxamine. Bromodeoxyuridine and 5-HT immunoreactivity
      confirmed cell survival and graft location 4 weeks posttransplantation. These
      results support the therapeutic potential of bioengineered serotonin-secreting
      cell lines in reducing chronic central pain following spinal cord injury.

PMID- 11573990
TI  - Volumetric changes in the anterior olfactory nucleus of the rat after neonatal
      olfactory deprivation.
AB  - The effect of olfactory deprivation in the postnatal development of the anterior
      olfactory nucleus (AON) was studied in 60-day-old rats which underwent unilateral
      naris closure after birth (postnatal day 1). Volumetric and morphometric analyses
      of the AON ipsilateral and contralateral to the closed naris were performed and
      data were statistically compared among them and with those of control animals.
      The volumes of the AONs and those of their subdivisions were calculated by the
      Cavalieri method and the area of the subdivisions was measured at seven
      established rostrocaudal levels. Whereas no statistically significant differences
      were detected between the ipsilateral and the contralateral AONs, comparison of
      these with controls revealed significant reductions in the volumes and dimensions
      of most AON subdivisions. The reduction was larger in the ipsilateral than in the
      contralateral AON and more pronounced in the rostralmost subdivisions (external
      and lateral) than in the caudal ones, the dorsal subdivision not being affected.
      These data demonstrate that the disruption of the normal afferent activity to one
      olfactory bulb has effects on the postnatal development of both the ipsilateral
      and the contralateral AONs. In addition, the most affected subdivisions were
      those that develop later and that receive the bulk of projections from the
      olfactory bulb, suggesting that the degree of maturity is an important factor in
      susceptibility to changes induced by reduced afferent activity. Finally, the
      results indicate that, contrary to the olfactory bulb, the contralateral AON
      cannot be used as a control structure in deprivation studies.

PMID- 11573991
TI  - Age-related changes in the N-methyl-D-aspartate receptor binding sites within the
      human basal ganglia.
AB  - The present study examined the regional differences in dopamine transporter
      binding sites and NMDA receptor complex binding based on autoradiographic images
      obtained in postmortem sections of human normal brain tissues. In middle-aged
      control tissues, high and comparable levels of [(3)H]CFT binding were observed in
      the caudate nucleus, putamen, and accumbens nucleus without significant
      alteration along the rostrocaudal axis and ventral and dorsal parts of these
      nuclei. In aging normal brain tissues, dopamine binding sites for [(3)H]CFT were
      significantly reduced in the caudate nucleus, putamen, and accumbens nucleus. l
      [(3)H]Glutamate, [(3)H]MK-801, and [(3)H]glycine binding to the NMDA receptor
      complex was lower in aging brain tissues than in middle-aged controls.
      Significant correlation did occur between age and [(3)H]CFT binding and between
      age and l-[(3)H]glutamate, [(3)H]MK-801, and [(3)H]glycine binding sites. These
      results demonstrate that the basal ganglia have age-associated reductions in
      dopamine transporter uptake and NMDA receptors. These data support hypoactive
      activity of the NMDA receptor complex system with advancing age. The dopamine
      transporter uptake and NMDA receptors appear to be vulnerable to the aging
      process in the basal ganglia.

PMID- 11573992
TI  - Subthalamic nucleus lesions are neuroprotective against terminal 6-OHDA-induced
      striatal lesions and restore postural balancing reactions.
AB  - Inactivation of the subthalamic nucleus (STN) by deep brain stimulation or
      lesioning can ameliorate symptoms in Parkinson' disease (PD) and may alter the
      underlying progressive degenerative process. We evaluated the effects of STN
      lesions in a terminal lesion model of PD in rats. Multiple intrastriatal 6-OHDA
      injections (4 x 7 microg) resulted in a partial loss of striatal TH-positive
      innervation (-30 to -40%) and nigral dopaminergic neurons (-60%), which was
      associated with behavioral deficits as observed in drug-induced rotational
      asymmetry, side-stepping, and postural balancing reactions. Unilateral ibotenic
      acid lesions of the STN did produce a 50-60% loss of STN neurons based on
      stereological analysis, which did not induce a functional impairment in
      rotational asymmetry or spontaneous sensorimotor behaviors. When STN lesions were
      performed 1 week prior to the 6-OHDA terminal striatal lesions, a significant
      rescue effect (+23%) on nigral dopaminergic neurons against terminal 6-OHDA
      neurotoxicity could be demonstrated, whereas striatal TH-positive fiber loss was
      not attenuated in these animals. In addition, animals with combined STN and
      striatal lesions exhibited a significant recovery in postural balancing reactions
      induced by 6-OHDA terminal lesions and did not show a significant impairment in
      any of the other behavioral parameters examined. Taken together, STN lesions can
      exert neuroprotective effects on nigral dopamine neurons in a partial lesion
      model of PD which result in recovery of spontaneous sensorimotor behavior. These
      findings may therefore provide new insights into the functional interaction
      between the glutamatergic and the dopaminergic neurotransmitter systems and
      foster novel therapeutic concepts for the early and middle phases of Parkinson's
      disease.

PMID- 11573993
TI  - Glial cells of the spinal cord and subcortical white matter up-regulate neuronal
      nitric oxide synthase in sporadic amyotrophic lateral sclerosis.
AB  - Several studies have suggested that excessive generation of nitric oxide (NO) may
      contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS). Recently,
      a selective induction of the neuronal isoform of nitric oxide synthase (nNOS) in
      glial cells has been reported in an animal model of familial ALS. We therefore
      examined in postmortem tissue the expression of nNOS in patients with sporadic
      ALS and patients without any history of neurological disease. Using
      immunohistochemistry, we found an up-regulation of nNOS in glial cells of the
      spinal cord and subcortical white matter in ALS patients compared to controls.
      The enhanced glial nNOS expression seen in ALS patients could conceivably
      contribute to motoneuronal degeneration through NO-mediated cytotoxic effects.

PMID- 11573994
TI  - Signaling for activity-dependent inhibitory synaptogenesis via the TrkB receptor.
AB  - Organotypic cerebellar cultures derived from newborn mice were incubated for 2
      weeks in vitro with antibodies that recognized the extracellular domains of the
      TrkB or TrkC receptor and were then examined by electron microscopy. Antibody
      activation of TrkB receptors resulted in development of an increased number of
      inhibitory Purkinje cell axosomatic synapses, while control numbers of axosomatic
      synapses were present in explants exposed to antibody to TrkC. Similar results
      had been obtained in previous studies when TrkB- and TrkC-specific ligands were
      applied to activity-blocked cerebellar cultures. These combined results are
      consistent with the concept that signaling for activity-dependent inhibitory
      synaptogenesis is via the TrkB receptor.

PMID- 11573995
TI  - 1-Boraadamantane blows its top, sometimes. The mono- and polyhomologation of 1
      boraadamantane.
AB  - [reaction: see text] 1-Boraadamantane.THF (3) reacts with 1 equiv of
      dimethylsulfoxonium methylide (4) to afford a monohomologated product. The
      polyhomologation of 1-boraadamantane.THF by ylide 4 followed by oxidative
      cleavage generates star polymethylene polymers incorporating a cyclohexane core.
      However, only one-third of the initiators lead to product formation, resulting in
      an observed degree of polymerization three times higher than expected. The
      polyhomologation of 3 was found to contain branch points after the fourth and
      fifth methylene insertions. At the branch points, the propagating species either
      terminate in tricyclic trialkylborane cages with collapsed, pyramidal inverted
      boron centers that are unreactive toward ylide or they continue in uninterrupted
      polymerization and eventually result in the formation of giant "tube-like"
      structures such as 5.

PMID- 11573996
TI  - Photochemical rearrangement of oxaziridines and nitrones in the hexahydroindole
      series: a convenient synthetic route to 1-azabicyclo[5.2.0]nonan-2-ones as novel
      RGD mimetics.
AB  - [reaction: see text] Photolysis of oxaziridines a or nitrones b provides a
      convenient synthetic route to fused bicyclic lactams c adequately substituted on
      both cycles A and B as scaffolds for mimicking conformationally constrained beta
      turn peptides as in the tripeptide RGD signaling motif of fibronectin.

PMID- 11573997
TI  - Selective phosphate protection: a novel synthesis of double-labeled
      oligonucleotides.
AB  - [structure: see text] A novel, selective labeling of oligonucleotides with two
      different reporter groups is described. The oligonucleotide is synthesized using
      a stable 2-(4-methoxybenzamido)ethyl protection for a selected internucleosidic
      thiophosphate (PS) and a labile 2-(N-isopropyl-4-methoxybenzamido)ethyl for the
      3'-terminal PS and internucleosidic phosphates. The latter group and the base
      protection are removed, and the 3'-terminal PS is labeled. The former protection
      is then cleaved by a prolonged ammonolysis, and the second reporter is introduced
      at the internucleosidic PS.

PMID- 11573998
TI  - A dendritic active site: catalysis of the Henry reaction.
AB  - [reaction: see text] Dendrimers containing an encapsulated tertiary amine were
      prepared by coupling tris(2-aminoethyl)amine with dendritic branches derived from
      L-lysine. These dendrimers were used as catalysts in the Henry (nitroaldol)
      reaction between 4-nitrobenzaldehyde and nitroethane, and their catalytic
      performance was compared with that of triethylamine. Attachment of the dendritic
      shell alters the rate of reaction and influences the syn:anti ratio of products.
      It is proposed that the dendritic shell generates an encapsulated catalytically
      active site, mimicking the behavior of a protein superstructure.

PMID- 11573999
TI  - Asymmetric synthesis of a fully protected ent-actinoidinic acid.
AB  - [structure: see text] The asymmetric synthesis of a fully protected ent
      actinoidinic acid derivative 14 is described. As key steps, an enantioselective
      deprotonation of an arene tricarbonylchromium(0) complex and a diastereoselective
      Suzuki coupling were applied. The asymmetric centers of the amino acid function
      were created via stereocontrolled Strecker reactions.

PMID- 11574000
TI  - Synthesis of beta- and gamma-carbolines by the palladium-catalyzed
      iminoannulation of internal alkynes.
AB  - [reaction: see text] A variety of substituted beta- and gamma-carbolines have
      been prepared in good to excellent yields by the annulation of internal
      acetylenes by the tert-butylimines of N-substituted 3-iodoindole-2
      carboxaldehydes and 2-haloindole-3-carboxaldehydes, respectively, in the presence
      of a palladium catalyst.

PMID- 11574001
TI  - Hydrosilylation of carbonyl compounds using a PhSeSiMe(3)/Bu(3)SnH/AIBN system.
AB  - [reaction: see text] When carbonyl compounds were allowed to react with phenyl
      trimethylsilyl selenide and tributylstannyl hydride in the presence of a
      catalytic amount of AIBN as a radical initiator, the hydrosilylation of the
      carbonyl compounds efficiently proceeded to give the corresponding silyl ethers
      in moderate to good yields.

PMID- 11574002
TI  - Organolanthanide-catalyzed intramolecular hydroamination/cyclization of amines
      tethered to 1,2-disubstituted alkenes.
AB  - [reaction: see text] This contribution reports the organolanthanide-catalyzed
      intramolecular hydroamination/cyclization of amines tethered to 1,2-disubstituted
      alkenes to afford the corresponding mono- and disubstituted pyrrolidines and
      piperidines by using coordinatively unsaturated complexes of the type (eta(5)
      Me(5)C(5))(2)LnCH(TMS)(2) (Ln = La, Sm), [Me(2)Si(eta(5)
      Me(4)C(5))(2)]NdCH(TMS)(2), [Et(2)Si(eta(5)-Me(4)C(5))(eta(5)
      C(5)H(4))]NdCH(TMS)(2), and [Me(2)Si(eta(5)-Me(4)C(5))((t)()BuN)]LnE(TMS)(2) (Ln
      = Sm, Y, Yb, Lu; E = N, CH) as precatalysts. [Me(2)Si(eta(5)
      Me(4)C(5))((t)BuN)]LnE(TMS)(2) mediates intramolecular hydroamination/cyclization
      of sterically demanding amino-olefins to afford disubstituted pyrrolidines in
      high diastereoselectivity (trans/cis = 16/1) and in good to excellent yield.

PMID- 11574003
TI  - Synthesis of polyoxygenated bicyclic systems containing medium-sized rings from
      carbohydrates via tandem metathesis of dienynes.
AB  - [reaction: see text] Highly functionalized (5-7), (5-8), and (6-8) ring systems
      have been prepared from carbohydrates via tandem ring-closing metathesis of
      dienynes.

PMID- 11574004
TI  - New stable neutral radical with intramolecular hydrogen bonding: synthesis and
      characterization of 2,5,8-tri-tert-butyl-7-hydroxy-6-oxophenalenoxyl.
AB  - A new stable neutral radical with intramolecular hydrogen bonding, 2,5,8-tri-tert
      butyl-7-hydroxy-6-oxophenalenoxyl, was synthesized from the corresponding
      dihydroxyphenalenone and isolated as a stable solid under air atmosphere at room
      temperature. The structure was unequivocally determined by means of IR spectra,
      ESR/ENDOR techniques, and DFT calculations.

PMID- 11574005
TI  - Difluorinated Danishefsky's diene: a versatile C(4) building block for the
      fluorinated six-membered rings.
AB  - [reaction: see text] A Mg(0)/Me(3)SiCl system was found to be effective for the
      preparation of difluoro Danishefsky's dienes 2, which involves selective C-F bond
      cleavage of trifluoromethyl ketones 3. Subsequent hetero Diels-Alder reactions of
      2 with aldehydes and imines gave a variety of fluorinated six-membered
      heterocycles.

PMID- 11574006
TI  - Total synthesis of (-)-callystatin A.
AB  - [reaction: see text] The enantioselective synthesis of callystatin A is
      described. The pivotal step in the synthesis is the stereoselective aldol
      reaction that generates the beta-hydroxy ketone moiety. Utilizing the allylic
      strain within the ethyl ketone precursor, we were able to generate the all-syn
      configuration of callystatin A. For the construction of the two diene moieties,
      both a Heck coupling and a Wittig reaction were employed.

PMID- 11574007
TI  - Highly satisfactory procedures for the Pd-catalyzed cross coupling of aryl
      electrophiles with in situ generated alkynylzinc derivatives.
AB  - [reaction: see text] Two new and very efficient procedures (Procedures A and B)
      are reported for the Pd-catalyzed cross coupling of aryl electrophiles with
      terminal alkynes via their in situ conversion into alkynylzinc derivatives.
      Procedure A is particularly valuable in cases where electron-deficient alkynes
      are used, while Procedure B is operationally simple and very satisfactory in less
      demanding cases.

PMID- 11574008
TI  - 8,9-Didehydrofluoranthenes as building blocks for the synthesis of extended
      polycyclic aromatic hydrocarbons (PAHs).
AB  - [reaction: see text] The synthesis of phenyl-substituted 8,9-dibromofluoranthene
      and p-dodecylphenyl-substituted 8,9-fluoranthene anthranilic acid is presented.
      Their synthetic potential as 8,9-didehydrofluoranthene precursors is demonstrated
      in combination with a new biscyclopentadienone by the synthesis of novel phenyl
      substituted PAHs with up to 14 annulated rings. The crystal structure of 7,16
      diphenylfluorantheno[8,9-k]fluoranthene is given.

PMID- 11574009
TI  - New uses of amino acids as chiral building blocks in organic synthesis.
AB  - [reaction: see text] N,N-Dibenzylamino aldehydes have emerged as a highly useful
      class of chiral building blocks in synthetic organic chemistry. We envisioned the
      transformation of the N,N -dibenzylamino aldehydes to the corresponding aldimines
      followed by diastereoselective methylene transfer with a sulfonium ylide to
      obtain alpha-amino aziridines in high yields.

PMID- 11574010
TI  - Use of odorless thiols: formal asymmetric Michael addition of hydrogen sulfide to
      alpha-substituted alpha,beta-unsaturated carbonyl compounds.
AB  - [reaction: see text] The Michael addition to alpha-substituted alpha,beta
      unsaturated esters and amides using complex A containing a chiral odorless thiol
      proceeded diastereoselectively. The Michael adducts were converted to beta
      mercapto esters and amides via a Wagner-Meerwein rearrangement with boron
      trifluoride etherate and a thiol exchange reaction using odorless 1
      dodecanethiol. This conversion constitutes a formal asymmetric Michael addition
      of hydrogen sulfide to alpha,beta-unsaturated carbonyl compounds using odorless
      thiols instead of the toxic hydrogen sulfide.

PMID- 11574011
TI  - An easy entry into berbane and alloyohimbane alkaloids via a 6-exo radical
      cyclization.
AB  - [reaction: see text] The pharmacologically important tetracyclic berbane and
      pentacyclic alloyohimbane structures were prepared efficiently in four steps
      including a stereoselective 6-exo radical cyclization using xanthates as the
      radical source.

PMID- 11574012
TI  - Effect of terminal group sterics and dendron packing on chirality transfer from
      the central core of a dendrimer.
AB  - [structure: see text] The conformational properties of intramolecularly hydrogen
      bonded dendrimers constructed from (S)-1,1'-bi-2-naphthol as a chiral central
      core are described. Circular dichroism studies revealed that chirality transfer
      to the periphery occurs only when sterically demanding terminal esters are
      employed and when packing interactions are present.

PMID- 11574013
TI  - An aldol-based approach to the asymmetric synthesis of L-callipeltose, the
      deoxyamino sugar of L-callipeltoside A.
AB  - [reaction: see text] The L-callipeltose subunit of L-callipeltoside A has been
      synthesized in 10 steps and 13% overall yield from D-threonine. The key steps are
      a highly diastereoselective Felkin anti aldol addition to a methyl ketone and a
      selective methylation of a secondary alcohol in the presence of a secondary
      carbamate.

PMID- 11574014
TI  - Regioselective allylzincation of alkenylboronate.
AB  - [reaction: see text] Boryl substitution on an olefin activates the olefinic
      double bond toward addition of an organozinc reagent. Addition of an allylic zinc
      reagent to an alkenylboronate thus takes place smoothly to afford a variety of
      gem-zincio/boryl species. Theoretical studies with density functional
      calculations on the reaction pathway revealed that the reaction proceeds via a
      zincio-ene reaction rather than a bora-Claisen rearrangement.

PMID- 11574015
TI  - Metal-directed formation of three-dimensional M(3)L(2) trigonal-bipyramidal
      cages.
AB  - [reaction: see text] The simple combination of two angular tritopic pyridine
      donor linkers (109 degrees bond angle) with three ditopic platinum acceptors (90
      degrees bond angle) leads to essentially quantitative formation of self-assembled
      M(3)L(2) trigonal-bipyramidal (TBP) supramolecular species.

PMID- 11574016
TI  - Strongly UV absorbing bifunctional azoalkanes.
AB  - [structure: see text] Two new anthracene-containing azoalkanes (1 and 2) absorb
      UV light 600 times more strongly than simple azoalkanes. Intramolecular energy
      transfer from excited singlet anthracene to the azo group is nearly complete, but
      despite the close proximity of the two chromophores, 1 and 2 continue to exhibit
      anthracene fluorescence. Thermolysis of these compounds in the presence of
      monomers affords fluorescent labeled polymers. Compounds 1 and 2 are the first
      azoalkanes to undergo induced decomposition in solution.

PMID- 11574017
TI  - Total synthesis of the microtubule-stabilizing agent (-)-laulimalide.
AB  - [structure: see text] The total synthesis of the potent microtubule-stabilizing
      anticancer agent (-)-laulimalide has been achieved in 27 steps and 2.9% overall
      yield. Notable features are the use of Jacobsen HDA chemistry for the
      enantioselective construction of the side chain dihydropyran, a
      diastereoselective aldol coupling using chiral boron enolate methodology, a
      Mitsunobu macrolactonization, and a Sharpless AE to introduce the epoxide onto
      des-epoxy-laulimalide.

PMID- 11574018
TI  - Highly efficient chiral-pool synthesis of (2S,4R)-4-hydroxyornithine.
AB  - [reaction: see text] A concise synthesis of the amino acid (2S,4R)-4
      hydroxyornithine is described. Starting from diprotected L-aspartic acid, the
      scaffold of the target compound is constructed in a three-step approach: an
      efficient alpha-nitroketone formation through acylation of nitromethane is
      followed by a diastereoselective reduction of the resulting ketone. In the last
      step, the nitro group is reduced to furnish the (2S,4R)-4-hydroxyornithine
      scaffold. This new approach to the title compound offers advantages to the
      synthetic pathways previously described.

PMID- 11574019
TI  - Enantioselective synthesis of (2-pyridyl)alanines via catalytic hydrogenation and
      application to the synthesis of L-azatyrosine.
AB  - [reaction: see text] A novel method for the synthesis of (2-pyridyl)alanines 2a-b
      was developed by converting (2-pyridyl)dehydroamino acid derivatives 1a-b to the
      corresponding N-oxides 3a-b followed by asymmetric hydrogenation using (R,R)
      [Rh(Et-DUPHOS)(COD)]BF(4) [(R,R)-6] catalyst and subsequent N-oxide reduction in
      80-83% ee. This methodology was applied to the total synthesis of L-azatyrosine
      [(+)-12], an antitumor antibiotic, starting from (5-benzyloxy)-2-pyridylmethanol
      (7), in >96% enantiomeric purity.

PMID- 11574020
TI  - A novel reactivity of SeO(2) with 1,3-dienes: formation of syn 1,2- and 1,4-diols
      via a facile C-Se bond oxidation.
AB  - [reaction: see text] A novel reaction between 1,3-dienes and selenium dioxide to
      give syn 1,2- and 1,4-diol cyclic selenites was studied in detail. This study
      indicates that an initial concerted [4 + 2] cycloaddition followed by a
      stereospecific carbon-selenium bond oxidation is involved in this unprecedented
      syn dihydroxy addition reaction mediated by selenium dioxide.

PMID- 11574021
TI  - Solid-phase synthesis of isoxazoles using vinyl ethers as chameleon catches.
AB  - [reaction: see text] Regioselective 1,3-dipolar cycloadditions of supported vinyl
      ethers R(1)C(=CH(2))O-CH(2)-polymer, prepared by the Tebbe olefination of
      R(1)CO(2)-CH(2)-polymer, with ethyl cyanoformate N-oxide gave supported
      isoxazoline derivatives. Release from the support under mild acidic conditions
      gave the isoxazoles ethyl 5-R(1)-isoxazole-3-carboxylates. Alternatively, further
      on-resin functionalization of the R(1) substituent using Suzuki coupling
      reactions and release from the support under acidic conditions gave more
      structurally diverse isoxazoles.

PMID- 11574022
TI  - Intramolecular Mannich reaction in the asymmetric synthesis of polysubstituted
      piperidines: concise synthesis of the dendrobate alkaloid (+)-241D and its C-4
      epimer.
AB  - [reaction: see text] The intramolecular Mannich reaction of delta-amino beta-keto
      esters with aldehydes and ketones is a new methodology for the synthesis of
      polysubstituted piperidines and is illustrated by the concise asymmetric
      synthesis of the dendrobate alkaloid (+)-241D and its C-4 epimer.

PMID- 11574023
TI  - (Z)-3-p-tolylsulfinylacrylonitriles as chiral dipolarophiles: reactions with
      diazoalkanes.
AB  - [reaction: see text] The dipolarophilic reactivity of enantiopure (Z)-3-p
      tolylsulfinylacrylonitriles (1) has been evaluated with diazoalkanes. 3
      Cyanopyrazoles are obtained when R = H, but with R = alkyl (Bn, n-Bu, and t-Bu)
      only one cycloadduct (4 or 5) is formed in high yield under mild conditions,
      therefore evidencing a complete control of the regioselectivity and the endo/exo
      and pi-facial selectivities. These reactions are a new straightforward entry to
      the synthesis of pyrazolines and related structures and reveal the excellent
      dipolarophilic features of (Z)-sulfinylacrylonitriles.

PMID- 11574024
TI  - Solid-phase synthesis of beta-amino ketones and six-ring carbamates via
      immobilized alpha-alkoxycarbonylamino sulfones.
AB  - [reaction: see text] beta-Amino ketones and substituted 1,3-oxazinan-2-ones have
      been synthesized utilizing polymer-bound and carbamate-linked alpha
      alkoxycarbonylamino sulfones. Key steps in the synthesis are the immobilization
      of the N-acylimine precursor, the Mannich-type addition of various nucleophiles,
      and the diastereoselective reduction of the resin-bound ketone.

PMID- 11574026
TI  - Synthesis of Delta(1)-1,2-diazetines via a Diels-Alder cycloaddition approach.
AB  - [reaction: see text] A novel method for the synthesis of Delta(1)-1,2-diazetines
      is presented. Diels-Alder cycloaddition of dienophile 4 with five dienes afforded
      cycloadducts in good to excellent yields. Four of the obtained cycloadducts were
      converted to the corresponding diazetines.

PMID- 11574025
TI  - Improved synthesis of C-terminal peptide thioesters on "safety-catch" resins
      using LiBr/THF.
AB  - [reaction: see text] The alkanesulfonamide "safety-catch" resin has proven useful
      for Fmoc-based synthesis of C-terminal peptide thioesters. We now report that the
      yield of isolated thioester can increase significantly when the cleavage reaction
      is carried out in 2 M LiBr/THF rather than DMF or THF. The largest effects are
      seen with problematic peptides that aggregate or form secondary structures on the
      resin.

PMID- 11574027
TI  - Total synthesis of (+/-)-hapalindole Q.
AB  - [reaction: see text] The total synthesis of the antibacterial and antimycotic
      alkaloid hapalindole Q has been achieved in eight steps and 12.4% overall yield.
      The key step involves a regio- and diastereoselective Diels-Alder reaction to
      afford a bicyclo[2.2.2]oct-2-ene. This cycloadduct was subsequently
      dihydroxylated, cleaved, and converted to the natural product.

PMID- 11574028
TI  - Intermolecular Pauson-Khand reactions of cyclopropene: a general synthesis of
      cyclopentanones.
AB  - [reaction: see text] The Pauson-Khand reaction of cyclopropene with a variety of
      terminal alkynes has been studied. The best reaction conditions involve NMO
      activation in CH(2)Cl(2) at -35 degrees C. In this way, 3-substituted
      bicyclo[3.1.0]hex-3-en-2-ones have been obtained in good to excellent yields. As
      a synthetic application, several types of substituted cyclopentenones have been
      prepared from these cycloadducts by protocols involving conjugate addition and
      reductive ring opening.

PMID- 11574029
TI  - Photochemistry of 3-substituted bicyclo[3.1.0]hex-3-en-2-ones. Regioselective
      synthesis of ortho-substituted phenols by Pauson-Khand reaction.
AB  - [reaction: see text] 3-Substituted bicyclo[3.1.0]hex-3-en-2-ones 3, easily
      obtained by Pauson-Khand reaction between terminal alkynes and cyclopropene, have
      been quantitatively converted into ortho-substituted phenols 4 by irradiation
      with UV light (350 nm). The kinetics and mechanism of this photochemical process
      have been studied by means of FT-IR and semiempirical (AM1 3x3 CI) calculations.

PMID- 11574030
TI  - Palladium-catalyzed cross-coupling reactions of in situ generated allylindium
      reagents with aryl halides.
AB  - [reaction: see text] In situ generated allylindium reagents from the reaction of
      1 equiv of indium with 1.5 equiv of allyl halides could be effective cross
      coupling partners in palladium-catalyzed cross-coupling reactions to aryl
      halides. The best results were obtained with 2% Pd(2)dba(3)CHCl(3) and 16% Ph(3)P
      in the presence of 3 equiv of LiCl in DMF at 100 degrees C.

PMID- 11574031
TI  - A novel nucleophilic substitution of in situ generated 3-tert-butyldimethyl-
      silyloxyalk-2-enylsulfonium salts with allylindium reagents.
AB  - [reaction: see text] In situ generated 3-tert-butyldimethylsilyloxyalk-2
      enylsulfonium salts derived from the reaction of alpha,beta-enones with dimethyl
      sulfide in the presence of TBSOTf undergo a novel nucleophilic substitution with
      in situ generated allylindium reagents from indium and allyl halides to give
      silyl enol ethers of delta,epsilon-unsaturated ketones, which correspond to
      Michael addition products, in good yields.

PMID- 11574032
TI  - "Fleximers". Design and synthesis of two novel split nucleosides.
AB  - [structure: see text] A new class of shape-modified nucleosides is introduced.
      The purine heterobases of adenosine and guanosine have been split into their
      imidazole and pyrimidine components, thereby introducing flexibility while
      retaining the elements necessary for recognition. As a consequence, these novel
      "fleximers" should find use as bioprobes for investigating enzyme-coenzyme
      binding sites as well as nucleic acid and protein interactions. Their design and
      synthesis is described.

PMID- 11574033
TI  - Highly effective transition structure designed catalyst for the enantio- and
      position-selective dihydroxylation of polyisoprenoids.
AB  - [structure: see text] The chiral monocinchona derivative shown, synthesized in
      one step from two efficiently prepared chiral building blocks, was designed under
      mechanistic guidance as a catalyst for the enantio- and position-selective
      dihydroxylation of the terminal isopropylidene group of polyisoprenoids. Its
      efficacy as a synthetic reagent for this purpose was demonstrated for several
      different substrates.

PMID- 11574034
TI  - A simple enantioselective synthesis of serratenediol.
AB  - [reaction: see text] A short synthesis of serratenediol is described, which
      involves a number of powerful key steps including (1) catalytic enantioselective
      syntheses of the phenyl sulfone and acylsilane shown above, (2) their coupling,
      and (3) further stereoselective cationic cyclizations.

PMID- 11574035
TI  - Model studies toward the total synthesis of the Lycopodium alkaloid
      spirolucidine.
AB  - [reaction: see text] A strategy for the synthesis of the spirocyclic core of
      spirolucidine was explored through a model study. The diene 4a was prepared and
      photolyzed to give the desired [2 + 2] photoadduct 17 containing the correct
      relative stereochemistry corresponding to spirolucidine.

PMID- 11574036
TI  - Self-association of facially amphiphilic methylene bridged glycoluril dimers.
AB  - [structure: see text] Facially amphiphilic derivatives of methylene bridged
      glycoluril dimers are a versatile model system for systematic studies of self
      assembly in water. Thorough physical organic characterization, including
      analytical ultracentrifugation, a technique rarely used in synthetic self
      assembly studies, allows us to conclude that this class of molecules undergoes
      hydrophobically driven self-association to yield tightly associated discrete
      dimeric assemblies.

PMID- 11574037
TI  - Enantioselective ruthenium-catalyzed ring-closing metathesis.
AB  - [reaction: see text] The first enantioselective ruthenium olefin metathesis
      catalysts have been prepared, and high enantiomeric excesses (up to 90%) are
      observed in the desymmetrization of achiral trienes. A model consistent with the
      stereochemical outcome of the reactions is described and suggests side-on olefin
      binding and reorganization of the halide ligands.

PMID- 11574038
TI  - Speech aeromechanics and the dysarthrias: implications for children with
      traumatic brain injury.
AB  - BACKGROUND: In addition to cognitive, linguistic, neurobehavioral, and physical
      challenges, children and adolescents with traumatic brain injury can have a
      dysarthria that compromises intelligibility and speaking effort. OBJECTIVE: The
      focus of this article is on an aeromechanical approach to understanding,
      evaluating, and treating the moderate-severe dysarthrias in these children.

PMID- 11574039
TI  - Development of the pediatric test of brain injury.
AB  - OBJECTIVE: The Pediatric Test of Traumatic Brain Injury (PTBI) (currently in its
      research edition) is a tool for assessing the cognitive-linguistic skills of
      school-aged children and adolescents in acute care and rehabilitation settings
      after traumatic brain injury. Development of the PTBI was motivated by the fact
      that, to date, no standardized test has been available to assess the full range
      of cognitive-linguistic impairments associated with pediatric brain injury. In
      this article we describe how the research edition of the PTBI was developed,
      provide rationale for the areas of assessment, discuss a plan for
      standardization, and illustrate its use with three children with TBI. DESIGN: The
      PTBI was constructed to sample the attention, memory, language, reading, writing,
      metalinguistic, and metacognitive skills that are particularly at risk in
      pediatric brain injury and that are relevant to the general education curriculum.
      MATERIAL: The test material for the PTBI was selected on the basis of clinical
      and experimental evidence that children and adolescents with TBI demonstrate a
      wide range of cognitive and language deficits. These first appear in the early
      stages of recovery and often persist but change over time. CONCLUSION: Our goal
      is to standardize the PTBI so it can be used to establish baseline behaviors and
      track cognitive-linguistic recovery.

PMID- 11574040
TI  - Longitudinal outcome of verbal discourse in children with traumatic brain injury:
      three-year follow-up.
AB  - PURPOSE: This study compared changes in discourse ability between two groups of
      children age 5 to 10 years after brain injury: those with severe traumatic brain
      injury (TBI) and those with mild/moderate injury over 3-year follow-up testing.
      MATERIALS AND METHODS: Forty-three children with TBI were recruited from a larger
      research project examining cognitive and linguistic recovery after injury. Twenty
      two of these patients had severe injuries and 21 sustained mild/moderate
      injuries. All children were presented an ordered sequence of pictures and asked
      to verbally produce a story/narrative discourse. Each child was then asked to
      produce a lesson relating to the story. RESULTS: The severe group performed
      significantly worse than the mild/moderate group when performance across all four
      discourse domains was considered. Both groups improved across time on selected
      discourse measures. Qualitative analysis suggested that the severe group showed
      differential rates of improvement across the individual discourse variables over
      the 3-year interval. CONCLUSIONS: Severe TBI can have a pernicious effect on
      discourse abilities in children years after injury compared with children with
      mild/moderate injuries. The major caveat is that the discourse measures must be
      sufficiently challenging when used to assess older children and children with
      milder forms of TBI.

PMID- 11574041
TI  - Comparison of literal, inferential, and intentional text comprehension in
      children with mild or severe closed head injury.
AB  - BACKGROUND: Children with head injury have impairments in pragmatic language at
      the level of both single words and texts. Text comprehension deficits are likely
      to be the more consequential for everyday and academic function, yet the relative
      magnitudes of literal and nonliteral text comprehension deficits have not been
      measured. DESIGN: We compared the magnitude of the impairment in three forms of
      text comprehension for children with mild or severe head injury relative with
      controls: literal language (understanding literal text information), inferential
      language (making pragmatic inferences, textual coherence inferences, or enriching
      inferences), and the language of mental states and intentions (eg, producing
      speech acts, appreciating irony, and understanding deception). MEASURES: Effect
      sizes were used to measure the magnitude of the difference between children with
      head injury and age-matched controls. RESULTS: Children with severe closed-head
      injury were significantly impaired on tasks of literal text understanding,
      inferencing, and intentionality. Children with mild head injury were impaired on
      some inferencing and all intentionality tasks, although they had no literal text
      comprehension deficits. CONCLUSIONS: For both groups, the greatest deficits (ie,
      the largest effect sizes) were on tasks requiring understanding of the language
      of mental states and intentions. The data bear on the long-term effects of
      childhood closed-head injury on text- and discourse-level language and also on
      the nature and timing of language rehabilitation in children with head injury.

PMID- 11574042
TI  - Social information processing in adolescents: data from normally developing
      adolescents and preliminary data from their peers with traumatic brain injury.
AB  - OBJECTIVE: To assess aspects of social information processing in naturalistic
      conversations, using online videotape tasks. DESIGN AND PARTICIPANTS: The tasks
      were administered to 60 normally developing (ND) subjects ages 13 to 21, and 10
      adolescents with traumatic brain injury (TBI). SETTING: University. MAIN OUTCOME
      MEASURE: Task accuracy scores and measures of reliability and validity. RESULTS
      AND CONCLUSIONS: ND group scores were generally high, without significant
      differences by race, sex or age. TBI group scores were significantly lower than
      ND group scores for both emotion recognition and detection of conversation
      skills. The results are discussed in light of the evaluation of pragmatic
      competence in adolescents with TBI.

PMID- 11574043
TI  - Pictures to print: a software scaffold to written literacy.
AB  - BACKGROUND: Successful school placements require effective written literacy
      skills. When a student has traumatic brain injury (TBI), written literacy
      instruction may need to be individualized and intense to facilitate optimal
      reintegration into the school program. Software products can provide a method
      that assists in creating the needed individualized, intense experiences. Written
      literacy-learning experiences span a continuum from preconventional messages
      expressed through pictures, to conventional printed expressions designed to
      convey meaning, to the literate writing needed to create stories and reports.
      DESIGN: This article is designed to familiarize rehabilitation and research
      professionals in TBI with the range of written literacy software and to stimulate
      clinical applications and research related to their use with students who have
      sustained a TBI.

PMID- 11574044
TI  - What does it take to collaborate with families affected by brain injury? A
      preliminary model.
AB  - BACKGROUND: Collaboration refers to a process in which family expertise is
      acknowledged and used to direct selection, implementation, and evaluation of
      treatment plans. Although the skills required to create collaborative
      partnerships with families are a mainstay of practice for certain rehabilitation
      disciplines, others have traditionally worked in client-clinician dyads that
      emphasize the role of the professional as responsible for client change. In
      addition, the existing collaborative models for working with families affected by
      brain injury require intensive resources and supports, making collaborative
      partnerships difficult to create within today's clinical and educational service
      delivery environments. RESULT: In this article, we report our efforts to create
      an accessible set of collaboration procedures for rehabilitation professionals
      working in clinical and educational settings with individuals with brain injury
      and their families. A 2-year, qualitative study with eight families led to the
      development of a preliminary model and prescriptive manual for applying
      collaborative principles to practice. CONCLUSION: We review the components of the
      model and implications for practice.

PMID- 11574046
TI  - St. John's wort.

PMID- 11574048
TI  - Antinociceptive and antiedematogenic properties and acute toxicity of Tabebuia
      avellanedae Lor. ex Griseb. inner bark aqueous extract.
AB  - BACKGROUND: Tabebuia avellanedae is a tree from the Bignoniaceae family. Commonly
      know as "pau d'arco" in Brazil, its inner bark is used as analgesic, anti
      inflammatory, antineoplasic and diuretic at the Brazilian northeast. A validation
      of the plant usage has not been previously performed. RESULTS: Antinociceptive
      and antiedematogenic effects of Tabebuia avellanedae Lor. ex Griseb. inner bark
      were measured by nociceptive experimental models in mice. A rat paw edema test
      induced by carrageenan (1%) was also performed in rats to access the plant's
      antiedematogenic effect. The inner bark aqueous extract, administered via oral in
      three different concentration, namely 100, 200 and 400 mg/Kg, reduced the
      nociception produced by acetic acid (0.6% in water, i.p.) by 49.9%, 63.7% and
      43.8%, respectively. The aqueous extract (200 and 400 mg/Kg, p.o.) reduced
      formalin (1%) effects only at the second phase of the experiment by 49.3% and
      53.7%, respectively. Naloxone (5 mg/Kg, i.p.) was not able to revert the extract
      effect, however caffeine (10 mg/Kg, i.p.) reverted its effect by 19.8% at the
      second phase of the formalin test. The aqueous extract (200 mg/Kg, p.o.)
      inhibited edema by 12.9% when we used the rat paw edema model. The acute toxicity
      was low in mice. CONCLUSION: The T. avellanedae inner bark aqueous extract
      presented antinociceptive and antiedematogenic activities at the used models,
      with a possible antinociceptive effect associated to the adenosine system.

PMID- 11574049
TI  - Theoretical and perceived balance of power inside Spanish public hospitals.
AB  - BACKGROUND: The hierarchical pyramid inside Spanish public hospitals was
      radically changed by the Health Reform Law promulgated in 1986. According to it,
      the manpower of the hospitals was divided into three divisions (Medical, Nursing,
      General Services/Administration), which from then on occupied the same level,
      only subject to the general manager. Ten years after the implementation of the
      law, the present study was designed in order to investigate if the legal changes
      had indeed produced a real change in the balance of power inside the hospitals,
      as perceived by the different workers within them. MATERIALS AND METHODS: A
      questionnaire was administered to 1,027 workers from four different public
      hospitals (two university-based and two district hospitals). The participants
      belonged to all divisions, and to all three operative levels (staff, supervisory
      and managerial) within them. The questionnaire inquired about the perceived power
      inside each division and hierarchical level, as well as about that of the other
      divisions and hierarchical levels. RESULTS: Every division attributed the least
      power to itself. The Nursing and the Administrative division attributed the
      highest power to the physicians, and these attributed the highest power to the
      General Services/Administrative division. All hierarchical levels (including the
      formal top of the pyramid) attributed significantly more power to the other than
      to them. CONCLUSIONS: More than ten years after the implementation of the new
      law, the majority of workers still perceive that the real power within the
      hospitals is held by the physicians (whereas these feel that it has shifted to
      the administrators). No division or hierarchical level believes it holds any
      significant degree of power, and this carries with it the danger of also not
      accepting any responsibility.

PMID- 11574051
TI  - Genomic and proteomic techniques applied to reproductive biology.
AB  - A report on the Frontiers in Reproduction Symposium 2001 'Reproductive genetics,
      genomics and proteomics: advances in genetic, molecular and bioinformatics
      techniques', Cambridge, USA, 30 June to 1 July, 2001.

PMID- 11574052
TI  - The miracle of microarray data analysis.
AB  - A report on the tenth Annual Bioinformatics and Genome Research meeting of the
      Cambridge Healthtech Institute's Beyond Genome 2001 series, San Francisco, USA,
      17-19 June 2001.

PMID- 11574053
TI  - Two C or not two C: recurrent disruption of Zn-ribbons, gene duplication, lineage
      specific gene loss, and horizontal gene transfer in evolution of bacterial
      ribosomal proteins.
AB  - BACKGROUND: Ribosomal proteins are encoded in all genomes of cellular life forms
      and are, generally, well conserved during evolution. In prokaryotes, the genes
      for most ribosomal proteins are clustered in several highly conserved operons,
      which ensures efficient co-regulation of their expression. Duplications of
      ribosomal-protein genes are infrequent, and given their coordinated expression
      and functioning, it is generally assumed that ribosomal-protein genes are
      unlikely to undergo horizontal transfer. However, with the accumulation of
      numerous complete genome sequences of prokaryotes, several paralogous pairs of
      ribosomal protein genes have been identified. Here we analyze all such cases and
      attempt to reconstruct the evolutionary history of these ribosomal proteins.
      RESULTS: Complete bacterial genomes were searched for duplications of ribosomal
      proteins. Ribosomal proteins L36, L33, L31, S14 are each duplicated in several
      bacterial genomes and ribosomal proteins L11, L28, L7/L12, S1, S15, S18 are so
      far duplicated in only one genome each. Sequence analysis of the four ribosomal
      proteins, for which paralogs were detected in several genomes, two of the
      ribosomal proteins duplicated in one genome (L28 and S18), and the ribosomal
      protein L32 showed that each of them comes in two distinct versions. One form
      contains a predicted metal-binding Zn-ribbon that consists of four conserved
      cysteines (in some cases replaced by histidines), whereas, in the second form,
      these metal-chelating residues are completely or partially replaced. Typically,
      genomes containing paralogous genes for these ribosomal proteins encode both
      versions, designated C+ and C-, respectively. Analysis of phylogenetic trees for
      these seven ribosomal proteins, combined with comparison of genomic contexts for
      the respective genes, indicates that in most, if not all cases, their evolution
      involved a duplication of the ancestral C+ form early in bacterial evolution,
      with subsequent alternative loss of the C+ and C- forms in different lineages.
      Additionally, evidence was obtained for a role of horizontal gene transfer in the
      evolution of these ribosomal proteins, with multiple cases of gene displacement
      'in situ', that is, without a change of the gene order in the recipient genome.
      CONCLUSIONS: A more complex picture of evolution of bacterial ribosomal proteins
      than previously suspected is emerging from these results, with major
      contributions of lineage-specific gene loss and horizontal gene transfer. The
      recurrent theme of emergence and disruption of Zn-ribbons in bacterial ribosomal
      proteins awaits a functional interpretation.

PMID- 11574054
TI  - A functional update of the Escherichia coli K-12 genome.
AB  - BACKGROUND: Since the genome of Escherichia coli K-12 was initially annotated in
      1997, additional functional information based on biological characterization and
      functions of sequence-similar proteins has become available. On the basis of this
      new information, an updated version of the annotated chromosome has been
      generated. RESULTS: The E. coli K-12 chromosome is currently represented by 4,401
      genes encoding 116 RNAs and 4,285 proteins. The boundaries of the genes
      identified in the GenBank Accession U00096 were used. Some protein-coding
      sequences are compound and encode multimodular proteins. The coding sequences
      (CDSs) are represented by modules (protein elements of at least 100 amino acids
      with biological activity and independent evolutionary history). There are 4,616
      identified modules in the 4,285 proteins. Of these, 48.9% have been
      characterized, 29.5% have an imputed function, 2.1% have a phenotype and 19.5%
      have no function assignment. Only 7% of the modules appear unique to E. coli, and
      this number is expected to be reduced as more genome data becomes available. The
      imputed functions were assigned on the basis of manual evaluation of functions
      predicted by BLAST and DARWIN analyses and by the MAGPIE genome annotation
      system. CONCLUSIONS: Much knowledge has been gained about functions encoded by
      the E. coli K-12 genome since the 1997 annotation was published. The data
      presented here should be useful for analysis of E. coli gene products as well as
      gene products encoded by other genomes.

PMID- 11574055
TI  - A rapid method to map mutations in Drosophila.
AB  - BACKGROUND: Genetic screens in Drosophila have provided a wealth of information
      about a variety of cellular and developmental processes. It is now possible to
      screen for mutant phenotypes in virtually any cell at any stage of development by
      performing clonal screens using the flp/FRT system. The rate-limiting step in the
      analysis of these mutants is often the identification of the mutated gene,
      however, because traditional mapping strategies rely mainly on genetic and
      cytological markers that are not easily linked to the molecular map. RESULTS:
      Here we describe the development of a single-nucleotide polymorphism (SNP) map
      for chromosome arm 3R. The map contains 73 polymorphisms between the standard FRT
      chromosome, and a mapping chromosome that carries several visible markers
      (rucuca), at an average density of one SNP per 370 kilobases (kb). Using this
      collection, we show that mutants can be mapped to a 400 kb interval in a single
      meiotic mapping cross, with only a few hundred SNP detection reactions. Discovery
      of further SNPs in the region of interest allows the mutation to be mapped with
      the same recombinants to a region of about 50 kb. CONCLUSION: The combined use of
      standard visible markers and molecular polymorphisms in a single mapping strategy
      greatly reduces both the time and cost of mapping mutations, because it requires
      at least four times fewer SNP detection reactions than a standard approach. The
      use of this map, or others developed along the same lines, will greatly
      facilitate the identification of the molecular lesions in mutants from clonal
      screens.

PMID- 11574056
TI  - On the species of origin: diagnosing the source of symbiotic transcripts.
AB  - BACKGROUND: Most organisms have developed ways to recognize and interact with
      other species. Symbiotic interactions range from pathogenic to mutualistic. Some
      molecular mechanisms of interspecific interaction are well understood, but many
      remain to be discovered. Expressed sequence tags (ESTs) from cultures of
      interacting symbionts can help identify transcripts that regulate symbiosis, but
      present a unique challenge for functional analysis. Given a sequence expressed in
      an interaction between two symbionts, the challenge is to determine from which
      organism the transcript originated. For high-throughput sequencing from
      interaction cultures, a reliable computational approach is needed. Previous
      investigations into GC nucleotide content and comparative similarity searching
      provide provisional solutions, but a comparative lexical analysis, which uses a
      likelihood-ratio test of hexamer counts, is more powerful. RESULTS: Validation
      with genes whose origin and function are known yielded 94% accuracy. Microbial
      (non-plant) transcripts comprised 75% of a Phytophthora sojae-infected soybean
      (Glycine max cv Harasoy) library, contrasted with 15% or less in root tissue
      libraries of Medicago truncatula from axenic, Phytophthora medicaginis-infected,
      mycorrhizal, and rhizobacterial treatments. Mycorrhizal libraries contained about
      23% microbial transcripts; an axenic plant library contained a similar proportion
      of putative microbial transcripts. CONCLUSIONS: Comparative lexical analysis
      offers numerous advantages over alternative approaches. Many of the transcripts
      isolated from mixed cultures were of unknown function, suggesting specificity to
      symbiotic metabolism and therefore candidates likely to be interesting for
      further functional investigation. Future investigations will determine whether
      the abundance of non-plant transcripts in a pure plant library indicates
      procedural artifacts, horizontally transferred genes, or other phenomena.

PMID- 11574057
TI  - Reassignment of specificities of two cap methyltransferase domains in the
      reovirus lambda 2 protein.
AB  - BACKGROUND: The reovirus lambda2 protein catalyzes mRNA capping, that is,
      addition of a guanosine to the 5' end of each transcript in a 5'-to-5'
      orientation, as well as transfer of a methyl group from S-adenosyl-L-methionine
      (AdoMet) to the N7 atom of the added guanosyl moiety and subsequently to the
      ribose 2'-O atom of the first template-encoded nucleotide. The structure of the
      human reovirus core has been solved at 3.6 A resolution, revealing a series of
      domains that include a putative guanylyltransferase domain and two putative
      methyltransferase (MTase) domains. It has been suggested that the order of
      domains in the lambda2 protein corresponds to the order of reactions in the
      pathway and that the m7G (cap 0) and the 2'-O-ribose (cap 1) MTase activities may
      be exerted by the MTase 1 and the MTase 2 domains, respectively. RESULTS: We show
      that the reovirus MTase 1 domain shares a putative active site with the
      structurally characterized 2'-O-ribose MTases, including vaccinia virus cap 1
      MTase, whereas the MTase 2 domain is structurally similar to glycine N-MTase.
      CONCLUSIONS: On the basis of our analysis of the structural details we propose
      that the previously suggested functional assignments of the MTase 1 and MTase 2
      domains should be swapped.

PMID- 11574058
TI  - Abundant protein domains occur in proportion to proteome size.
AB  - BACKGROUND: Conserved domains in proteins have crucial roles in protein
      interactions, DNA binding, enzyme activity and other important cellular
      processes. It will be of interest to determine the proportions of genes
      containing such domains in the proteomes of different eukaryotes. RESULTS: The
      average proportion of conserved domains in each of five eukaryote genomes was
      calculated. In pairwise genome comparisons, the ratio of genes containing a given
      conserved domain in the two genomes on average reflected the ratio of the
      predicted total gene numbers of the two genomes. These ratios have been verified
      using a repository of databases and one of its subdivisions of conserved domains.
      CONCLUSIONS: Many conserved domains occur as a constant proportion of proteome
      size across the five sequenced eukaryotic genomes. This raises the possibility
      that this proportion is maintained because of functional constraints on
      interacting domains. The universality of the ratio in the five eukaryotic genomes
      attests to its potential importance.

PMID- 11574059
TI  - Molecular archeology of an SP100 splice variant revisited: dating the
      retrotranscription and Alu insertion events.
AB  - BACKGROUND: SP100 is a nuclear protein that displays a number of alternative
      splice variants. In Old World monkeys, apes and humans one of these variants is
      extended by a retroprocessed pseudogene, HMG1L3, whose antecedent gene is a
      member of the family of high-mobility-group proteins, HMG1. This is one of only a
      few documented cases of a retropseudogene being incorporated into another gene as
      a functional exon. In addition to the HMG1L3 insertion, Old World monkey genomes
      also contain an Alu sequence within the last SP100-HMG intron. PCR amplification
      of the 3' end of the SP100 gene using genomic DNAs from human and New World and
      Old World monkey species, followed by direct sequencing of the amplicons has made
      dating the HMG1L3 and Alu insertion events possible. RESULTS: PCR amplifications
      confirm that the HMG1L3 retrotransposition into the SP100 locus occurred after
      divergence of New World and Old World monkey lineages, some 35-40 million years
      ago. PCR amplification also shows that an upstream Alu sequence was inserted in
      the last SP100-HMG intron after divergence of the Old World monkey and ape
      lineages. Direct sequencing of the Alu in five Old World monkey species places
      the latter event at around 19 million years ago. Finally, ten single base
      mutations and one deletion in the Alu differentiate African from Asian Old World
      monkey species. CONCLUSIONS: PCR and DNA sequence analysis of 'genetic fossils'
      such as retropseudogenes and Alu elements in primates give details as to the
      timing of such events and can reveal sequence features useful for other molecular
      phylogenetic applications.

PMID- 11574061
TI  - Being in the right location at the right time.
AB  - Taking each coding sequence from the human genome in turn and identifying the
      subcellular localization of the corresponding protein would be a significant
      contribution to understanding the function of each of these genes and to
      deciphering functional networks. This article highlights current approaches aimed
      at achieving this goal.

PMID- 11574060
TI  - The nuclear pore complex.
AB  - Nuclear pore complexes, the conduits for information exchange between the nucleus
      and cytoplasm, appear broadly similar in eukaryotes from yeast to human.
      Precisely how nuclear pore complexes regulate macromolecular and ionic traffic
      remains unknown, but recent advances in the identification and characterization
      of components of the complex by proteomics and genomics have provided new
      insights.

PMID- 11574062
TI  - New clues to the puzzle of mammalian sex determination.
AB  - WT1 and SOX9 are transcription factors with critical roles in mammalian sex
      determination and gonadal development. Recent studies in vivo clarify the roles
      of two alternative splice isoforms of WT1, and demonstrate that SOX9 can induce
      male sex determination.

PMID- 11574063
TI  - The trappist's approach to pathfinding: elucidating brain wiring using secretory
      trap mutagenesis.
AB  - A key problem in using genetics to dissect the wiring of the mammalian brain lies
      in discovering which of the billions of neural connections have been disrupted by
      a particular mutation. A novel gene-trap approach targets the genes involved in
      brain wiring and labels the axons of neurons expressing those genes, enabling the
      effects of mutations to be observed directly.

PMID- 11574064
TI  - The PITP family of phosphatidylinositol transfer proteins.

PMID- 11574065
TI  - Accelerated refolding of subtilisin BPN' by tertiary-structure-forming mutants of
      its propeptide.
AB  - The propeptide of subtilisin BPN', which functions as an intramolecular chaperone
      and a temporary inhibitor of subtilisin, is unique in that it acquires its three
      dimensional structure by formation of a complex with the cognate protease. We
      previously showed that the successive amino acid replacements Ala47-->Phe, Gly13-
      >Ile, and Val65-->Ile in the propeptide to increase its hydrophobicity resulted
      in formation of a tertiary structure, accompanied by increased ability to bind to
      the protease and increased resistance to proteolysis. In this study, we examined
      the effects of these tertiary-structure-forming mutations on the intramolecular
      chaperone activity of the propeptide. The successive amino acid replacements
      mentioned above were introduced into pro-subtilisin*, possessing a Ser221-->Ala
      mutation in the catalytic residue. Refolding experiments were started by rapid
      dilution of the denatured pro-subtilisin*, and formation of tertiary structure in
      subtilisin was monitored kinetically by increase in tryptophan fluorescence. The
      wild-type pro-subtilisin* was found to refold with a rate constant of 4.8 x 10(
      3) s(-1) in the equation describing an intramolecular process. The Ala47-->Phe
      replacement in the propeptide resulted in a 1.2-fold increase in the rate
      constant of subtilisin refolding. When the additional replacement Gly13-->Ile was
      introduced, refolding of subtilisin was substantially accelerated, and its
      kinetics could be fitted to a double exponential process composed of a fast phase
      with a rate constant of 2.1 x 10(-2) s(-1) and a slow phase with a rate constant
      of 4.5 x 10(-3) s(-1). The rate constant of the fast phase was increased slightly
      by a further replacement, Val65-->Ile. Since the slow phase is considered to
      correspond to proline isomerization, we concluded that tertiary-structure-forming
      mutations in the propeptide produce positive effects on its intramolecular
      chaperone activity through acceleration of the propeptide-induced formation of
      the tertiary structure of subtilisin BPN'.

PMID- 11574066
TI  - A novel human metalloprotease synthesized in the liver and secreted into the
      blood: possibly, the von Willebrand factor-cleaving protease?
AB  - We identified a novel metalloprotease, which could be responsible for cleaving
      the Tyr842-Met843 peptide bond of von Willebrand factor (vWF). This
      metalloprotease was purified from Cohn Fraction-I precipitate of human pooled
      plasma by the combination of gel filtration, DEAE chromatography, and preparative
      polyacrylamide gel electrophoresis in the presence of SDS. The NH2-terminal amino
      acid sequence of the isolated protein was: AAGGILHLELLVAVGPDVFQAHQEDTRRY. Based
      on this sequence, we searched human genomic and EST databases, and identified
      compatible nucleotide sequences. These results suggested that this protein is a
      novel metalloprotease, a member of the family of a disintegrin and
      metalloprotease with thrombospondin type-1 motifs (ADAMTS), and its genomic DNA
      was mapped to human chromosome 9q34. Multiple human tissue northern blotting
      analysis indicated that the mRNA encoding this protease spanned approximately 5
      kilobases and was uniquely expressed in the liver. Furthermore, we determined the
      cDNA sequence encoding this protease, and found that this protease was comprised
      of a signal peptide, a proregion followed by the putative furin cleavage site, a
      reprolysin-type zinc-metalloprotease domain, a disintegrin-like domain, a
      thrombospondin type-1 (TSP1) motif, a cysteine-rich region, a spacer domain, and
      COOH-terminal TSP1 motif repeats.

PMID- 11574067
TI  - Effects of flavin-binding motif amino acid mutations in the NADH-cytochrome b5
      reductase catalytic domain on protein stability and catalysis.
AB  - Porcine NADH-cytochrome b5 reductase catalytic domain (Pb5R) has the
      RXY(T/S)+(T/S) flavin-binding motif that is highly conserved among the
      structurally related family of flavoprotein reductases. Mutations were introduced
      that alter the Arg(63), Tyr(65), and Ser(99) residues within this motif. The
      mutation of Tyr(65) to either alanine or phenylalanine destabilized the protein,
      produced an accelerated release of FAD in the presence of 1.5 M guanidine
      hydrochloride, and decreased the k(cat) values of the enzyme. These results
      indicate that Tyr(65) contributes to the stability of the protein and is
      important in the electron transfer from NADH to FAD. The mutation of Ser(99) to
      either alanine or valine, and of Arg(63) to either alanine or glutamine increased
      both the K(m) values for NADH (K(m)(NADH)) and the dissociation constant for
      NAD(+) (K(d)(NAD+)). However, the mutation of Ser(99) to threonine and of Arg(63)
      to lysine had very little effect on the K(m)(NADH) and K(d)(NAD+) values, and
      resulted in small changes in the absorption and circular dichroism spectra. These
      results suggest that the hydroxyl group of Ser(99) and the positive charge of
      Arg(63) contribute to the maintenance of the properties of FAD and to the
      effective binding of Pb5R to both NADH and NAD(+). In addition, the mutation of
      Arg(63) to either alanine or glutamine increased the apparent K(m) values for
      porcine cytochrome b5 (Pb5), while changing Arg(63) to lysine did not. The
      positive charge of Arg(63) may regulate the electron transfer through the
      electrostatic interaction with Pb5. These results substantiate the important role
      of the flavin-binding motif in Pb5R.

PMID- 11574068
TI  - Aggregation and chemical reaction in hen lysozyme caused by heating at pH 6 are
      depressed by osmolytes, sucrose and trehalose.
AB  - We examined the effects of osmolytes, sucrose and trehalose, on the deterioration
      of hen lysozyme as a model protein. Sucrose and trehalose depressed the
      aggregation of lysozyme molecules caused by heating at 100 degrees C at pH 6.
      Since lysozyme was fully denatured under these conditions, the effects of sucrose
      and trehalose on the denatured state of lysozyme were investigated using reduced
      S-alkylated lysozyme, a model of denatured hen lysozyme. From analyses of
      circular dichroism spectra and fluorescence spectra, sucrose and trehalose were
      found to induce alpha-helical conformations and some tertiary structures around
      tryptophan residues in the reduced S-alkylated lysozyme. Moreover, these
      compounds also depressed chemical reactions such as deamidation and racemization,
      which often cause the deterioration of proteins, on the reduced S-alkylated
      lysozyme. Therefore, the data suggest that sucrose and trehalose have a
      propensity to depress such deterioration as the aggregation of protein molecules
      or chemical reactions in proteins by inducing some tertiary structures (including
      alpha-helical structures) in the polypeptide chain.

PMID- 11574069
TI  - Recognition of mitochondrial protein precursor lacking arginine at position -2 by
      mitochondrial processing peptidase: processing of bovine cytochrome P450(SCC)
      precursor.
AB  - Mitochondrial processing peptidase (MPP) specifically cleaves off the N-terminal
      presequence of the mitochondrial protein precursor. Previous studies demonstrated
      that Arg at position -2 from the cleavage site, which is found among many
      precursors, plays a critical role in recognition by MPP. We analyzed the
      structural elements of bovine cytochrome P450 side-chain cleavage enzyme
      precursor [pre-P450(SCC)], which has Ala at position -2, for recognition by MPP.
      Replacement of Ala position -2 of pre-P450(SCC) with Arg resulted in an increase
      in the cleavage rate. Replacement with Gly caused a reduction in the cleavage
      rate and the appearance of an additional cleavage site downstream of the
      authentic site. A pre-P450(SCC) mutant with Met at position -2 retained cleavage
      efficiency equal to that of the wild type. These results indicate that -2 Ala of
      pre-P450(SCC) is recognized by MPP as a determinant for precise cleavage, and
      that the amino acid at -2 is required to have a straight methylene chain for
      interaction with the S(2) site. The preference for distal basic residues, a
      hydrophobic residue at +1, and hydroxyl residues at +2 and +3, was almost the
      same as those of the precursors with Arg at -2, indicating that the recognition
      mechanism of pre-P450(SCC) by MPP is essentially the same as that of the
      precursors with Arg at position -2.

PMID- 11574070
TI  - Regulation of Ca(2+)/calmodulin-dependent protein kinase kinase alpha by cAMP
      dependent protein kinase: I. Biochemical analysis.
AB  - Ca(2+)/calmodulin-dependent protein kinases (CaM-kinases) I and IV are activated
      upon phosphorylation of their Thr(177) and Thr(196), respectively, by the
      upstream Ca(2+)/calmodulin-dependent protein kinases CaM-kinase kinase alpha and
      beta, and deactivated upon dephosphorylation by protein phosphatases such as CaM
      kinase phosphatase. Recent studies demonstrated that the activity of CaM-kinase
      kinase alpha is decreased upon phosphorylation by cAMP-dependent protein kinase
      (PKA), and the relationship between the inhibition and phosphorylation of CaM
      kinase kinase alpha by PKA has been studied. In the present study, we demonstrate
      that the activity of CaM-kinase kinase alpha toward PKIV peptide, which contains
      the sequence surrounding Thr(196) of CaM-kinase IV, is increased by incubation
      with PKA in the presence of Ca(2+)/calmodulin but decreased in its absence, while
      the activity toward CaM-kinase IV is decreased by incubation with PKA in both the
      presence and absence of Ca(2+)/calmodulin. Six phosphorylation sites on CaM
      kinase kinase alpha, Ser(24) for autophosphorylation, and Ser(52), Ser(74),
      Thr(108), Ser(458), and Ser(475) for phosphorylation by PKA, were identified by
      amino acid sequence analysis of the phosphopeptides purified from the tryptic
      digest of the phosphorylated enzymes. The presence of Ca(2+)/calmodulin
      suppresses phosphorylation on Ser(52), Ser(74), Thr(108), and Ser(458) by PKA,
      but accelerates phosphorylation on Ser(475). The changes in the activity of the
      enzyme upon phosphorylation appear to occur as a result of conformational changes
      induced by phosphorylation on several sites.

PMID- 11574071
TI  - Regulation of Ca(2+)/calmodulin-dependent protein kinase kinase alpha by cAMP
      dependent protein kinase: II. Mutational analysis.
AB  - We previously reported that rat brain Ca(2+)/calmodulin-dependent protein kinase
      (CaM-kinase) IV is inactivated by cAMP-dependent protein kinase (PKA) [Kameshita,
      I. and Fujisawa, H. (1991) Biochem. Biophys. Res. Commun. 180, 191-196]. In the
      preceding paper, we demonstrated that changes in the activity of CaM-kinase IV by
      PKA results from the phosphorylation of CaM-kinase kinase alpha by PKA and
      identified six phosphorylation sites, Ser(24) for autophosphorylation, and
      Ser(52), Ser(74), Thr(108), Ser(458), and Ser(475) for phosphorylation by PKA. In
      the present study, a causal relationship between the phosphorylation and change
      in the activity toward PKIV peptide has been studied using mutant enzymes with
      amino acid substitutions at the six phosphorylation sites. The following
      conclusions can be drawn from the experimental results: (i) Phosphorylation of
      Ser74 and/or unidentified sites causes an increase in activity; (ii)
      phosphorylation of Thr(108) or Ser(458) causes a decrease in the activity; (iii)
      the inhibitory effect of the phosphorylation of Thr(108) is canceled by the
      stimulatory effect of the phosphorylation, but that of Ser(458) is not; and (iv)
      the inhibitory effects of Thr(108) and Ser(458) are synergistic. In contrast to
      the activity toward PKIV peptide, the activity toward CaM-kinase IV appears to be
      decreased by the phosphorylation of Thr(108), but not significantly affected by
      the phosphorylation of Ser(458).

PMID- 11574072
TI  - Functions and ATP-binding responses of the twelve histidine residues in the TF1
      ATPase beta subunit.
AB  - The C2 proton signals of all (twelve) histidine residues of the TF1 beta subunit
      in the 1H-NMR spectrum have been identified and assigned by means of pH change
      experiments and site-directed substitution of histidines by glutamines. pH and
      ligand titration experiments were carried out for these signals. Furthermore, the
      ATPase activity of the reconstituted alpha3beta3gamma complex was examined for
      the twelve mutant beta subunits. Two of three conserved histidines, namely, His
      119 and 324, were found to be important for expression of the ATPase activity.
      The former fixes the N-terminal domain to the central domain. His-324 is involved
      in the formation of the interface essential for the alpha3beta3gamma complex
      assembly. The other conserved residue, His-363, showed a very low pK(a),
      suggesting that it is involved in the tertiary structure formation. On the
      binding of a nucleotide, only the signals of His-173, 179, 200, and 324 shifted.
      These histidines are located in the hinge region, and its proximity, of the beta
      subunit. This observation provided further support for the conformational change
      of the beta monomer from the open to the closed form on the binding of a
      nucleotide proposed by us [Yagi et al. (1999) Biophys. J. 77, 2175-2183]. This
      conformational change should be one of the essential driving forces in the
      rotation of the alpha3beta3gamma complex.

PMID- 11574073
TI  - Limited proteolysis of filamin is catalyzed by caspase-3 in U937 and Jurkat
      cells.
AB  - Members of the caspase family have been implicated as key mediators of apoptosis
      in mammalian cells. However, few of their substrates are known to have
      physiological significance in the apoptotic process. We focused our screening for
      caspase substrates on cytoskeletal proteins. We found that an actin binding
      protein, filamin, was cleaved from 280 kDa to 170, 150, and 120 kDa major N
      terminal fragments, and 135, 120, and 110 kDa major C-terminal fragments when
      apoptosis was induced by etoposide in both the human monoblastic leukemia cell
      line U937, and the human T lymphoblastic cell line Jurkat. The cleavage of
      filamin was blocked by a cell permeable inhibitor of caspase-3-like protease, Ac
      DEVD-cho, but not by an inhibitor of caspase-1-like protease, Ac-YVAD-cho. These
      results suggest that filamin is cleaved by a caspase-3-like protease. To examine
      whether caspase-3 cleaves filamin in vitro, we prepared a recombinant active form
      of caspase-3 directly using a Pichia pastoris overexpression system. When we
      applied recombinant active caspase-3 to the cell lysate of U937 and Jurkat cells,
      filamin was cleaved into the same fragments seen in apoptosis-induced cells in
      vivo. Platelet filamin was also cleaved directly from 280 kDa to 170, 150, and
      120 kDa N-terminal fragments, and the cleavage pattern was the same as observed
      in apoptotic human cells in vivo. These results suggest that filamin is an in
      vivo substrate of caspase-3.

PMID- 11574074
TI  - Structural analysis of the sugar chains of human urinary thrombomodulin.
AB  - The sugar chains of human urinary thrombomodulin were studied. N- and O-linked
      sugar chains were simultaneously liberated by hydrazinolysis followed by N
      acetylation and were tagged with 2-aminopyridine. Then the structures of the N-
      and O-linked pyridylamino (PA-) sugar chains were analyzed by two-dimensional
      sugar mapping combined with exoglycosidase digestion. The major N-linked sugar
      chains of human urinary thrombomodulin were found to be monosialo- and
      disialofucosylbiantennary chains, while the major O-linked sugar chain was +/
      Siaalpha2-3Galbeta1-3(+/-Siaalpha2-6)GalNAc. Thrombomodulin also contained the
      reported structure SO4-3GlcAbeta1-3Galbeta1-3(+/-Siaalpha2-6)Galbeta1-4Xyl [H.
      Wakabayashi, S. Natsuka, T. Mega, N. Otsuki, M. Isaji, M. Naotsuka, S. Koyama, T.
      Kanamori, K. Sakai, and S. Hase (1999) J. Biol. Chem. 274, 5436-5442]. In
      addition to these sugar chains, a single Glc was linked to Ser 287.

PMID- 11574075
TI  - Antibody-antigen interactions measured by surface plasmon resonance: global
      fitting of numerical integration algorithms.
AB  - The interactions between adenylate kinase (AK) and a monoclonal antibody against
      AK (McAb3D3) were examined by means of optical biosensor technology, and the
      sensograms were fitted to four models using numerical integration algorithms. The
      interaction of a solution of McAb3D3 with immobilized AK follows a double
      exponential function and the data fitted well to an inhomogeneous ligand model.
      The interaction of a solution AK with immobilized McAb3D3 follows a single
      exponential function and the data fitted well to a pseudo-first order reaction
      model. The true association constants of AK binding to McAb3D3 in solution were
      obtained from competition BIAcore measurements. The difference in results
      obtained with solid-phase BIAcore and competition BIAcore may be due to rebinding
      of the dissociated analyte to the immobilized surface. The results obtained with
      BIAcore are compared to those obtained by ELISA methods. We suggest that the best
      method for analysis of BIAcore data is direct, global fitting of sensorgrams to
      numerical integration algorithms corresponding to the different possible models
      for binding.

PMID- 11574076
TI  - Compartmentalization of choline and acetylcholine metabolism in cultured
      sympathetic neurons.
AB  - To determine the relative contribution of cell bodies and distal axons to the
      production of acetylcholine, we used retinoic acid to induce a cholinergic
      phenotype in compartmented cultures of rat sympathetic neurons. When [3H]choline
      was given to cell bodies/proximal axons for 24 h, 98% of the radiolabel was
      recovered as choline, phosphocholine, CDP-choline and phosphatidylcholine,
      whereas only 1 to 2% of the radiolabel was incorporated into acetylcholine.
      Choline taken up by cell bodies and transported to axons is poorly utilized for
      acetylcholine biosynthesis. In contrast, when distal axons were supplied with
      [3H]choline, 11% of the radiolabel was recovered in acetylcholine after 24 h, the
      remainder being incorporated into precursors/metabolites of phosphatidylcholine.
      The lack of acetylcholine synthesis in cell bodies/proximal axons could not be
      ascribed to an absence of choline acetyltransferase activity in this region of
      the neurons, since the specific activity of this enzyme was similar in cell
      bodies/proximal axons and distal axons. The rate of choline uptake by distal
      axons (15.3 4.4 nmol/5 min/mg protein) was approximately 10-fold greater than by
      cell bodies/proximal axons (1.6 0.8 nmol/5 min/mg protein). Moreover, choline
      uptake into distal axons was inhibited by 74.5% by hemicholinium-3, and by 80.1%
      by removal of Na(+) from the medium. In contrast, choline uptake by cell
      bodies/proximal axons was not significantly inhibited by hemicholinium-3 or Na(+)
      removal. These results suggest that the majority of axonal acetylcholine is
      synthesized in distal axons/axon terminals from choline taken up by a high
      affinity choline transporter in distal axons.

PMID- 11574077
TI  - Transcriptional regulation of the Bacillus subtilis bscR-CYP102A3 operon by the
      BscR repressor and differential induction of cytochrome CYP102A3 expression by
      oleic acid and palmitate.
AB  - The adjacent yrhI and yrhJ genes were identified by the Bacillus subtilis genome
      sequencing project. We now report that yrhJ (renamed CYP102A3) encodes a
      cytochrome P450 and that yrhI (renamed bscR) encodes a repressor that negatively
      regulates the transcription of the bscR-CYP102A3 operon. The transcriptional
      initiation site of bscR has been mapped by primer extension analysis. An 18-bp
      perfect palindromic sequence centered 65.5 bp downstream from the transcriptional
      initiation site of bscR has been identified as the binding site for BscR by gel
      mobility shift assays. Base substitutions in the 18-bp inverted repeat resulted
      in derepression of the bscR-xylE transcriptional fusion in vivo. bscR-xylE fusion
      studies and Northern blot analysis revealed that oleic acid and palmitate could
      induce the expression of the bscR-CYP102A3 operon to a considerable extent.
      However, only oleic acid was capable of preventing the binding of BscR to its
      operator DNA in vitro, suggesting that the induction of CYP102A3 expression by
      oleic acid and palmitate in B. subtilis might be mediated through different
      mechanisms.

PMID- 11574078
TI  - Peer review.
AB  - Peer review is essential for ensuring quality medical care. In the 1980s a
      physician-plaintiff prevailed in lawsuit filed against peer reviewers who
      excluded the physician from a hospital's medical staff. The peer reviewers had
      acted to preserve their own economic interests. A multimillion-dollar verdict
      against the peer reviewers destroyed the community's only multispecialty practice
      and received national attention. Congress reacted by passing the Health Care
      Quality Improvement Act that granted sweeping, legal immunity for peer reviewers
      but also created the National Practitioner's Data Bank. The combination of the
      establishment of a public repository for physicians malpractice and medical staff
      privileging activity in combination with the near complete legal protection of
      peer reviewers has converted peer review from an evaluative to a punitive
      process. The peer review process and the laws that govern it should be reformed
      to regain its ability to improve and assure quality without being a threat to
      physicians.

PMID- 11574079
TI  - What do master surgeons think of surgical competence and revalidation?
AB  - BACKGROUND: There has been on-going debate and public interest in surgical
      competence in recent years. METHODS: A Delphi reiterative opinion survey was
      conducted among master surgeons on selection of surgical trainees, methods of
      assessment of progress of surgical trainees, and revalidation of established
      consultant surgeons. RESULTS: Selection-the current methods of trainee selection
      were considered inadequate and in need of revision. The important attributes
      recognized by group are cognitive factors, innate dexterity, and personality.
      Important aspects of personality include decision-making ability, insight, team
      spirit, and emotional stability. Assessment during training-the majority view was
      that this should be based on clinical judgement/skills, operative skills, and
      cognitive ability. Assessment of technical ability should be based on
      standardized checklists. Research within training programs was encouraged but
      academic achievement does not reflect surgical competence. There was a majority
      verdict for an exit clinical examination. Revalidation-the group agreed on the
      need for competence checks during the professional career of surgeons. These
      should cover knowledge, clinical, operative, and humanistic skills; but expressed
      concern on the feasibility of a revalidation system that can reliably assess the
      range of skills needed for surgical competence. There was a majority vote against
      an internal appraisal system. External assessment by nationally appointed
      'assessors' was considered preferable. CONCLUSIONS: Both selection and assessment
      of surgical trainees require changes and standardization. Although revalidation
      is necessary, concern was expressed on the reliability and validity of existing
      and proposed systems.

PMID- 11574080
TI  - Needle aspiration of breast abscesses.
AB  - BACKGROUND: Traditional treatment of breast abscesses involves incision and
      drainage, with and without ultrasound guidance. These procedures cause
      considerable discomfort and morbidity for the patient. This study was conducted
      to determine whether needle aspiration of breast abscesses without ultrasound
      guidance was an effective treatment modality. METHOD: In our prospective study,
      30 patients with 33 breast abscesses were treated by needle aspiration of pus,
      oral antibiotics, and repeat aspiration, if necessary. All were outpatients, and
      ultrasonography was not used. Twenty-five of the 30 patients were lactating.
      RESULTS: Eighteen patients required only a single aspiration, 9 patients required
      multiple aspirations, and 6 patients required incision and drainage (overall cure
      rate, 82%). Those patients in whom needle aspiration was successful had a
      significantly smaller volume of pus on initial aspiration (4.0 mL versus 21.5 mL,
      P = 0.002) and were more likely to have presented earlier than those not cured by
      aspiration (5.0 days versus 8.5 days, P = 0.006). CONCLUSION: Needle aspiration
      without ultrasound guidance is an effective treatment for breast abscesses.

PMID- 11574081
TI  - Is pancreaticoduodenectomy with mesentericoportal venous resection safe and
      worthwhile?
AB  - BACKGROUND: Whether or not superior mesentericoportal venous resection (SM-PVR)
      associated with pancreaticoduodenectomy (PD) is safe and worthwhile has not been
      fully confirmed. The aim of the present study was to investigate results of this
      surgical procedure performed for pancreatic head and periampullary neoplasms.
      METHODS: As a first analysis, postoperative morbidity and mortality after PD with
      (n = 31) or without SM-PVR (n = 119) were investigated in 150 patients with
      pancreatic head and periampullary neoplasms. As a second analysis, rates of
      margin-negative resection and survival after SM-PVR (n = 21) and without SM-PVR
      (n = 66) were compared in 87 patients with pancreatic ductal adenocarcinoma of
      the pancreatic head. In these patients undergoing SM-PVR (n = 21), survival rate
      was investigated in patients who did (n = 13) and did not (n = 8) undergo a
      margin-negative resection. RESULTS: In the first analysis, duration of surgery
      and volume of blood transfused perioperatively were higher in patients undergoing
      SM-PVR. However, mortality, morbidity rates, and mean hospital stay did not
      differ between patients who did undergo SM-PVR (31 patients, 3.2%, 48.4%, and
      22.2 days, respectively) and who did not (119 patients, 2.5%, 47.1%, 25.9 days,
      respectively). No postoperative death occurred in the recent part of the present
      study, since 1994, in patients undergoing SM-PVR. In the second analysis of
      pancreatic ductal adenocarcinoma, rates of margin-negative resection and 2-year
      survival did not significantly differ between patients who did and did not
      undergo SM-PVR (62% and 22%, respectively, versus 73% and 24%). In patients
      undergoing SM-PVR, survival rate was significantly higher for patients undergoing
      a margin-negative resection (n = 13) than for patients undergoing a macroscopic
      or microscopic margin-positive resection (n = 8, 2-year survival = 57.1% versus
      0%, P <0.05). CONCLUSION: PD combined with SM-PVR can be performed safely. This
      surgical procedure is followed by a promising survival rate and can be
      recommended in order to obtain a margin-negative resection; however, candidates
      for SM-PVR should be carefully selected.

PMID- 11574082
TI  - External metallic circle in microsurgical anastomosis of common bile duct.
AB  - BACKGROUND: Biliary stricture development is one of the most serious problems
      following biliary tract surgery. Here, we present a new technique for biliary
      tract reconstruction with an external metallic circle, and the results of this
      new technique in a rat model. METHODS: Twelve male Sprague-Dawley rats (250 to
      300 g) were divided into two groups. After transection of the bile duct, standard
      bile duct reconstruction (without the metallic circle) was performed in group 1
      and reconstruction with the external metallic (silver) circle was performed in
      group 2. At the end of the fourth month, clinical, laboratory biochemical, and
      histopathologic parameters were compared between the groups. RESULTS: Serum
      concentrations of alkaline phosphatase (ALP) and operation time were higher in
      group 1 than in group 2. Differences were statistically significant. In
      histopathologic examination, biliary duct stricture was seen in group 1. Foreign
      body reaction and fibrosis in the bile duct wall were seen in group 2.
      CONCLUSION: An external metallic circle prevents development of biliary stricture
      after primary end-to-end bile duct anastomosis in this rat model.

PMID- 11574083
TI  - Operative findings in recurrent hernia after a Lichtenstein procedure.
AB  - BACKGROUND: Recurrence after inguinal herniorraphy continues to be a problem,
      although the Lichtenstein technique (anterior, open fixated sheet mesh) is
      associated with reduced recurrence rates. Recurrence after Lichtenstein repair is
      suspected to be caused by insufficient fixation and overlap at the pubic
      tubercle. METHODS: A review was made of 87 records from operations for recurrence
      after a previous Lichtenstein procedure, based upon national and large area data
      bases, recording 95% (Denmark) and 50% (Sweden) of all inguinal hernia
      operations. RESULTS: Direct recurrences were found in 62%, whereas the remaining
      recurrences were either indirect (17%), femoral (13%), or other/unclassified
      (8%). CONCLUSION: The most plausible explanation for the development of the
      direct recurrences is an insufficient medial mesh fixation and overlap over the
      pubic tubercle. Avoidance of more than half of the recurrences after the
      Lichtenstein repair may be obtained by increased attention to this specific
      technical aspect of the operation.

PMID- 11574084
TI  - Laparoscopic skills training.
AB  - BACKGROUND: The purpose of this study was to quantify the learning curve of a
      previously validated laparoscopic skills curriculum. METHODS: Second-year medical
      students (MS2, n = 11) and second (PGY2, n = 11) and third (PGY3, n = 6) year
      surgery residents were enrolled into a curriculum using five video-trainer tasks.
      All subjects underwent baseline testing, training (30 minutes per day for 10
      days), and final testing. Scores were based on completion time. The relationship
      between task completion time and the number of practice repetitions was examined.
      Improvement (the difference in baseline and final performance) amongst groups was
      compared by one-way analysis of variance using the baseline score as a covariate;
      P <0.05 indicated significance. RESULTS: Baseline scores were not significantly
      different. Final scores were significantly better for MS2s versus PGY3s. Adjusted
      improvement was significantly larger for the MS2s compared with PGY2s and PGY3s,
      and for PGY2s compared with PGY3s. The mean number of repetitions corresponding
      to a predicted 90th percentile score was 32. CONCLUSION: Inexperienced subjects
      benefit the most from skills training. For maximal benefit, we recommend that
      each task be practiced for at least 30 to 35 repetitions.

PMID- 11574085
TI  - The role of blinded interviews in the assessment of surgical residency
      candidates.
AB  - BACKGROUND: Interview assessments of surgical residency candidates may be biased
      by prior knowledge of objective data. METHODS: Each candidate (site 1: n = 88;
      site 2: n = 44) underwent two interviews, one by faculty members informed only of
      a candidate's medical school, the second with prior knowledge of the complete
      application. Interviewers (site 1: n = 28; site 2: n = 14) independently rated
      candidates overall and on nine qualitative characteristics. RESULTS: At site 1
      only, overall ratings were significantly more favorable for unblinded than
      blinded interviews (23.0 +/- 17.7 versus 32.6 +/- 23.1, P < 0.01). Blinded and
      unblinded overall ratings correlated -0.01 (P = 0.90) and 0.31 (P = 0.05) at
      sites 1 and 2, respectively. At site 1 only, overall ratings correlated
      significantly with USMLE scores, but in opposite directions for blinded (r =
      0.32, P = 0.003) versus unblinded interviews (r = -0.32, P = 0.003). CONCLUSION:
      Interview assessments may be influenced by objective data, and faculty and
      program variables. The value of blinded interviewing may vary as a function of
      individual program characteristics.

PMID- 11574086
TI  - Outcome of extra-anatomic vascular reconstruction in orthotopic liver
      transplantation.
AB  - BACKGROUND: Portal venous and hepatic arterial reconstruction are critical to
      successful outcomes in orthotopic liver transplantation (OLT). With portal vein
      thrombosis or inadequate hepatic arterial inflow, extra-anatomic vascular
      reconstruction is required. However, the clinical outcomes following extra
      anatomic vascular reconstruction are largely unknown. METHODS: To determine the
      outcomes associated with extra-anatomic vascular reconstruction, we performed a
      retrospective review of 205 OLT recipients transplanted between 1995 and 2000.
      RESULTS: Extra-anatomic portal venous inflow was based upon the recipient
      superior mesenteric vein using donor iliac vein graft in a retrogastric position
      (n = 12). Extra-anatomic arterial inflow was based on recipient infrarenal aorta
      using donor iliac artery graft through the transverse mesocolon (n = 25). OLT
      with routine anatomic vascular construction served as control (n = 168). Extra
      anatomic vascular reconstruction was not associated with increased morbidity,
      mortality, operating room time, length of stay, or thrombosis. CONCLUSION: We
      conclude that extra-anatomic vascular conduits are associated with excellent long
      term outcomes and provide acceptable alternatives for vascular reconstruction in
      OLT.

PMID- 11574087
TI  - Sclerosing encapsulating peritonitis after orthotopic liver transplantation.
AB  - BACKGROUND: The etiology of abdominal cocoon (a rare cause of intestinal
      obstruction) is unknown. It has occurred in adolescent girls, cirrhotic patients
      after peritoneal-venous shunting, and patients undergoing peritoneal dialysis. We
      report our experience with patients after orthotopic liver transplantation (OLT).
      METHODS: Five patients (4 male, 1 female, aged 16 to 57 years) underwent OLT (3
      whole liver, 2 right lobe grafts) and subsequently developed abdominal cocoon.
      RESULTS: All developed pyrexia by 66 +/- 21 hours posttransplant. Additional
      symptoms (epigastric discomfort and intermittent vomiting) occurred 12 +/- 10
      days later. Bacterial peritonitis was confirmed by microbiology in 2 cases and
      diagnosed by exclusion in the others. C-reactive protein levels were persistently
      elevated in all patients (35 to 82 mg/L). While abdominal CT consistently
      demonstrated marked ascites with the small intestine confined to a particular
      area of the abdomen, intestinal contrast studies and ultrasound were not
      diagnostic. All patients underwent surgical removal of the cocoon membrane by 58
      +/- 22 days after transplant. CONCLUSIONS: Sclerosing peritonitis may complicate
      liver transplantation and occurs because of low-grade intra-abdominal sepsis.

PMID- 11574088
TI  - Pancreas after kidney transplants.
AB  - BACKGROUND: For certain uremic diabetic patients, a sequential transplant of a
      kidney (usually from a living donor) followed by a cadaver pancreas has become an
      attractive alternative to a simultaneous transplant of both organs. The purpose
      of this study was to compare outcomes with simultaneous pancreas-kidney (SPK)
      versus pancreas after kidney (PAK) transplants to determine advantages and
      disadvantages of the two procedures. METHODS: Between January 1, 1994, and June
      30, 2000, we performed 398 cadaver pancreas transplants at our center. Of these,
      193 were SPK transplants and 205 were PAK transplants. We compared these two
      groups with regard to several endpoints, including patient and graft survival
      rates, surgical complications, acute rejection rates, waiting times, length of
      hospital stay, and quality of life. RESULTS: Overall, surgical complications were
      more common for SPK recipients. The total relaparotomy rate was 25.9% for SPK
      recipients versus 15.1% for PAK recipients (P = 0.006). Leaks, intraabdominal
      infections, and wound infections were all significantly more common in SPK
      recipients (P = 0.009, P = 0.05, and P = 0.01, respectively, versus PAK
      recipients). Short-term pancreas graft survival rates were similar between the
      two groups: at 1 year posttransplant, 78.0% for SPK recipients and 77.9% for PAK
      recipients (P = not significant). By 3 years, however, pancreas graft survival
      differed between the two groups (74.1% for SPK and 61.7% for PAK recipients),
      although this did not quite reach statistical significance (P = 0.15). This
      difference in graft survival seemed to be due to increased immunologic losses for
      PAK recipients: at 3 years posttransplant, the incidence of immunologic graft
      loss was 16.2% for PAK versus 5.2% for SPK recipients (P = 0.01). Kidney graft
      survival rates were, however, better for PAK recipients. At 3 years after their
      kidney transplant, kidney graft survival rates were 83.6% for SPK and 94.6% for
      PAK recipients (P = 0.001). The mean waiting time to receive the pancreas
      transplant was 244 days for SPK and 167 days for PAK recipients (P = 0.001).
      CONCLUSIONS: PAK transplants are a viable option for uremic diabetics. While long
      term pancreas graft results are slightly inferior to SPK transplants, the
      advantages of PAK transplants include the possibility of a preemptive living
      donor kidney transplant, better long-term kidney graft survival, significantly
      decreased waiting times, and decreased surgical complication rates. Use of a
      living donor for the kidney transplant expands the donor pool. Improvements in
      immunosuppressive regimens will hopefully eliminate some of the difference in
      long-term pancreas graft survival between SPK and PAK transplants.

PMID- 11574089
TI  - Preservation of the inferior mesenteric artery in colorectal resection for
      complicated diverticular disease.
AB  - BACKGROUND: Preservation of the inferior mesenteric artery (IMA) and
      consequential blood flow to the rectum would reduce the risk of leakage of a
      colorectal anastomosis. METHODS: One hundred and sixty-three patients undergoing
      left colectomy for complicated diverticular disease of the colon were randomly
      placed into two groups: A, n = 86; and B, n = 77. In group A, the integrity of
      the IMA was preserved by artery skeletization (IMAS); in group B, the IMA was
      divided at its origin. Variables recorded included duration of the surgical
      procedure, need for blood transfusion, length of hospital stay, operative
      mortality and morbidity, staple-ring disruption, and radiologic and clinical
      leakage. Anastomotic stenosis and recurrence of diverticular disease were noted.
      RESULTS: Surgical time was superior in the IMAS group. Radiologic and clinical
      leakages were significantly higher in group B (P = 0.02, P = 0.03, respectively).
      In group A a significant lower number of staple-ring disruptions was observed,
      evolving into clinical dehiscence. CONCLUSION: Preserving the natural blood
      supply to the rectum and the ensuing use of a healthy well-nourished rectal stump
      are suggested as the main aspects of IMAS in preventing and healing leakage of
      colorectal anastomosis.

PMID- 11574090
TI  - Functional results two years after laparoscopic rectopexy.
AB  - BACKGROUND: Rectopexy is one of the accepted treatment options for full-thickness
      rectal prolapse, but the details of the technique remain controversial. This unit
      has adopted a laparoscopic approach as an alternative to open surgery, and has
      used three techniques: mesh, suture, and resection. This retrospective study
      compares the long-term outcome. METHODS: From 1993 to 1995, 14 patients underwent
      a laparoscopic posterior mesh rectopexy. From 1996 to 1999, 34 patients underwent
      laparoscopic suture rectopexy with (n = 18) or without sigmoid resection (n =
      16). RESULTS: There was no postoperative mortality, and morbidity was similar in
      the three groups, ranging from 11 to 19%. The mean follow-up was 47, 24, and 20
      months for mesh, suture, and resection rectopexy, respectively. During follow-up,
      1 patient in each group developed mucosal prolapse. There was no difference
      between the three groups for incontinence rate, which improved in more than 75%
      of patients who had impaired continence preoperatively. Postoperative
      constipation was observed in 2 patients (11%) after resection rectopexy, in 10
      (62%) after suture rectopexy (P < 0.01 versus resection), and in 9 (64%) after
      mesh rectopexy (P < 0.01 versus resection). CONCLUSIONS: Our results show that
      the addition of sigmoid resection to laparoscopic rectopexy is safe and could
      contribute to reduce the risk of severe constipation after operation.
      Laparoscopic mesh rectopexy confers no advantage over the sutured technique,
      which we now use as our fixation method of choice.

PMID- 11574091
TI  - A new technique for esophagojejunostomy after total gastrectomy for gastric
      cancer.
AB  - BACKGROUND: The critical part of any operation involving a proximal gastric
      resection is the esophageal anastomosis. Leakage from this anastomosis is one of
      the main reasons for postoperative morbidity and death after gastrectomy.
      Application of the double-stapling technique affords many of the same advantages
      that it does for low rectal tumors, especially in obese patients with narrow
      costal margins. METHODS: A new technique for esophagojejunostomy after total
      gastrectomy for gastric cancer is described. RESULTS: This technique has been
      used in 3 patients. At a follow-up of 22 months, there have been no anastomotic
      leaks or evidence of clinical stenoses. CONCLUSIONS: This technique minimizes
      manipulation and dissection around the distal esophagus. Not only does this make
      the operation easier, but it also allows for a longer proximal resection margin.
      Possibly this will result in lower rates of esophageal breakdown.

PMID- 11574092
TI  - The role of macroscopic classification in nodular-type hepatocellular carcinoma.
AB  - BACKGROUND: Little has been reported on the role of macroscopic classification of
      hepatocellular carcinoma (HCC). We hypothesized that macroscopic classification
      of HCC might have a strong correlation with long-term prognosis after
      hepatectomy. METHODS: Four hundred and four patients with a macroscopically
      nodular type of HCC who underwent a hepatectomy were studied. The patients were
      divided into three groups: single nodular (SN) group (n = 312); single nodular
      with extranodular growth (SNEG) group (n = 52); and confluent multinodular (CMN)
      group (n = 40). Clinicopathological variables were compared among the three
      groups. The patient survival rate was also compared among the three groups.
      Finally, a multivariate analysis was performed to clarify the independent
      significant variables of the long-term prognosis. To confirm the consistency of
      the results in small-size HCC, the same analyses were made using patients whose
      tumor size was equal to or less than 3 cm in diameter. RESULTS: The alpha
      fetoprotein value, tumor size, and rate of absolute noncurative operation in the
      SNEG group were higher than in other groups. The positive rate of both portal
      vein invasion of cancer cells and intrahepatic metastasis in the SN group was
      lower than those in other groups. The rate of poorly differentiated histology in
      the SN group was lower than in the other groups. Patient survival in the SNEG
      group was worst among the three groups. However, patient survival showed no
      significant difference between the SN and CMN groups. The multivariate analysis
      showed that the presence of intrahepatic metastasis, the macroscopic
      classification of SNEG type, and absolute noncurative operation were independent
      poor prognostic indicators. The results for patients with small HCCs measuring
      equal to or less than 3 cm in diameter were quite similar to the results for the
      other patients. CONCLUSIONS: Among the three subtypes of macroscopically nodular
      type of HCCs, the SNEG type showed higher rates of portal vein invasion of cancer
      cells, intrahepatic metastasis, and poorly differentiated histology. The patient
      survival rate in the SNEG type was worst, and the SNEG type was an independent
      poor prognostic indicator. The macroscopic classification of HCC, especially the
      SNEG type, helps predict the long-term outcome after hepatectomy.

PMID- 11574093
TI  - Renal cell carcinoma metastatic to pancreas.

PMID- 11574094
TI  - A rare association between acromegaly and pheochromocytoma.
AB  - The occurrence of multiple endocrine tumors is rare; however, they may be found
      with hereditary diseases such as multiple endocrine neoplasia (MEN). The
      endocrine tumors involved with these diseases are well documented. We present a
      case of a patient with a pheochromocytoma and a growth hormone (GH) secreting
      pituitary adenoma. This association is not described with any of the known MEN
      syndromes. The association may be a cross-over MEN syndrome or a secondarily
      induced GH-secreting pituitary adenoma from a pheochromocytoma producing growth
      hormone releasing hormone (GHRH) instead of catecholamines.

PMID- 11574095
TI  - Spatial assessment by magnetic resonance cholangiopancreatography for
      preoperative imaging in partial pancreatic head resection.
AB  - BACKGROUND: Partial pancreatic head resection has been recommended for
      intraductal papillary mucinous tumor (IPMT). We report the usefulness of
      preoperative assessment by magnetic resonance cholangiopancreatography (MRCP)
      compared with endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We
      studied 12 cases of surgically resected IPMT in the pancreatic head. The MRCP and
      ERCP images were interpreted, and we examined the detection rate of each imaging
      technique for the Wirsung duct, the Santorini duct, the entire cystic tumor, and
      the communication between the tumor and the ducts. RESULTS: In all cases MRCP
      correctly identified the entire cystic tumor, and the communication between the
      tumor and the pancreatic ducts was seen in 64% of cases. In contrast, the
      detection rate by ERCP of the entire cystic tumor and of the communication
      between the cystic tumor and the ducts was only 8% and 18%, respectively.
      CONCLUSION: MRCP clearly showed the relationship of the cystic tumor and the
      pancreatic ducts and was very useful for preoperative imaging for partial
      pancreatic head resection.

PMID- 11574096
TI  - Successful late management of spontaneous esophageal rupture using T-tube
      mediastinoabdominal drainage.
AB  - BACKGROUND: Spontaneous esophageal rupture is extremely rare, and early symptoms
      of the disease are similar to those of emergency diseases of the chest and
      abdomen. The diagnosis and treatments are often delayed, resulting in an
      unfavorable outcome in some cases. METHODS: We performed improved T-tube drainage
      for spontaneous esophageal rupture in 5 patients between 1995 and 1999. Our
      improved method was a modified procedure of the reported method of Abbott et al,
      as follows: a T-tube was inserted into the esophagus. A separate stab incision
      was made in the abdominal wall, and the long limb of the T-tube was brought out
      through this incision ensuring that the course of the T-tube intra-abdominally
      was short and straight, with some slack to allow for postoperative abdominal
      distension. An advantage of this method was that it facilitated healing of the
      fistula after removal of the T-tube. RESULTS: All patients were treated with a
      satisfactory outcome. CONCLUSION: This improved T-tube drainage was technically
      very easy and safe method for spontaneous esophageal rupture in severe cases.

PMID- 11574097
TI  - Significance of preoperative elevation of serum C-reactive protein as an
      indicator of prognosis in esophageal carcinoma.
AB  - BACKGROUND: Preoperative elevation of serum C-reactive protein (CRP) has been
      reported to be a prognostic indicator in gastric carcinoma and colorectal
      carcinoma. The aim of this study was to establish the significance of
      preoperative elevation of serum CRP as an indicator of prognosis in patients with
      esophageal carcinoma. METHODS: Two hundred sixty-two patients with esophageal
      carcinoma who had been treated by esophageal resection and reconstruction of
      digestive tracts were evaluated, excluding patients with neoplasms in other
      organs. Preoperative serum CRP was measured, and the relation between the
      elevation of serum CRP and the clinicopathological factors and prognosis of the
      patients was investigated. RESULTS: The mean size of the tumors and the
      proportions of lymph node metastasis and lymphatic invasion were significantly
      larger in patients with preoperative elevation of serum CRP than in patients
      without preoperative elevation of serum CRP (5.8 +/- 2.5 cm versus 4.8 +/- 2.5
      cm, P <0.01, 59.5% versus 35.4%, P <0.001, and 35.7% versus 23.6%, P <0.05,
      respectively). 1-, 3-, and 5-year survival rates in patients with preoperative
      elevation of serum CRP (60.6%, 18.4%, and 11.5%, respectively) were significantly
      lower than those in patients without preoperative elevation of serum CRP (88.7%,
      70.9%, and 68.4%, respectively; P <0.0001). Multivariate analysis demonstrated
      that the preoperative elevation of serum CRP was an independent prognostic factor
      in esophageal carcinoma (P <0.0001). CONCLUSIONS: The preoperative serum
      elevation of CRP can be a marker of the malignant potential of the tumor and an
      independent prognostic indicator in esophageal carcinoma.

PMID- 11574098
TI  - Continuing medical education in developing countries.

PMID- 11574099
TI  - Marked anemic hypoxia deteriorates cerebral hemodynamics and brain metabolism
      during massive intracerebral hemorrhage.
AB  - The present study was undertaken to investigate the influence of imposed anemic
      hypoxia on cerebral hemodynamics and metabolism in a condition of massive ICH.
      Two groups of eight dogs, with a target hemoglobin concentration of 12 g/dl in
      nonanemic and 6 g/dl in anemic group, were included. Before the onset of the
      insult, anemic group had a significant reduction (p<0.05) in cerebral
      arteriovenous oxygen content difference (AVDO2), accompanied with a significant
      rise (p<0.05) in flow velocity (FV) of the basilar artery and cerebral extraction
      fraction of oxygen (CEO2) and a lower brain-tissue lactate clearance than did
      nonanemic group. Shortly after ICH, both groups displayed significant reductions
      (p<0.05) in FV, CEO2 and AVDO2, and simultaneous rises in arteriovenous lactate
      concentrations. In nonanemic group, the CEO2 and AVDO2 gradually returned after
      an initial decrease, and then the arteriovenous lactate concentrations slowly
      decreased. In contrast, anemic group showed progressive reductions in CEO2 and
      AVDO2 associated with persistent rises in arteriovenous lactate concentrations.
      Consequently, anemic group exhibited significantly greater brain-tissue lactate
      clearances (p<0.05), occurring at 10 min and 5 h postinjury, than did nonanemic
      group, although the former had relatively higher levels of CEO2 up to 3 h
      postinjury. We conclude that anemic hypoxia modulates a favorable change in
      cerebral hemodynamics and oxygenation, while it progressively deteriorates after
      an initial reduction during massive ICH, thus facilitating cerebral anaerobic
      glycolysis in biphasic periods. These results point to a complex interaction
      between cerebral hemodynamics, oxygen supply and glycolysis homeostasis upon the
      addition of anemic hypoxia in severe stress conditions of the brain.

PMID- 11574100
TI  - Polymorphic markers in MHC class II/III region: a study on Italian patients with
      myasthenia gravis.
AB  - With an Italian case series of 81 Italian patients and 130 controls, we analysed
      associations between myasthenia gravis (MG) and genetic polymorphisms in the MHC
      class II/III region. Increases in the frequency of the TNF-B*1, C4A*Q0, C4B*1,
      DRB1*03 supratype, which is likely part of the 8.1 ancestral haplotype, were
      maximal in females with early onset (EO) MG vs. controls [p<0.05, relative risk
      (RR)=9.9]. These patients showed neither a significantly high frequency of thymic
      hyperplasia, nor high levels of serum anti-acethylcholine receptor antibodies.
      The DRB1*03 allele was absent in patients with thymoma; however, in comparison
      with controls, occurrence of this marker was frequent in MG patients (p<0.005;
      RR=6.2), more frequent in females (p<0.005; RR=7.8) and most frequent in EOMG
      female patients (p<0.005; RR=15.1). Analysis of the TNF-B*1, C4A*Q0, C4B*1,
      DRB1*03 supratype and its recombinants showed that the MHC region between C4 and
      TNF might contain genes that influence susceptibility to MG in females.
      Polymorphic markers within the supratype, e.g. TNF-B*1 and C4A*Q0, might
      contribute to pathogenetically significant abnormalities in immune responses in a
      subset of female MG patients. The combined effect of other intervening genes
      cannot be excluded.

PMID- 11574101
TI  - Association of APOE epsilon4 allele with survival in amyotrophic lateral
      sclerosis.
AB  - APOE epsilon4 allele is associated with poorer outcome in degenerative
      neurological diseases. Its role in amyotrophic lateral sclerosis (ALS) is still
      unclear. The aim of the present study was to further analyze the association of
      APOE epsilon4 allele with progression and survival of ALS. One hundred
      consecutive ALS patients (53 males) and 133 controls were genotyped for the APOE
      epsilon4 allele. The association of this allele with survival to death or
      tracheostomy was analyzed by Kaplan-Meier survival analysis. The frequency of the
      APOE epsilon4 allele in ALS patients was slightly higher (15.1%) than in the
      control group (10.9%). Patients with or without an APOE epsilon4 allele had a
      similar age of onset and frequency of bulbar onset. There was a significant
      shortening of the 50% probability of survival (by 32 months) in patients carrying
      the APOE epsilon4 allele (p=0.03). In conclusion, carrying an APOE epsilon4
      allele is a poor prognostic factor in ALS. This is compatible with a role of
      apolipoprotein on neuronal survival and repair.

PMID- 11574102
TI  - Proton magnetic resonance spectroscopy and transcranial magnetic stimulation for
      the detection of upper motor neuron degeneration in ALS patients.
AB  - Transcranial magnetic stimulation (TMS) was compared to proton magnetic resonance
      spectroscopy (1H-MRS) for the detection of upper motor neuron loss or dysfunction
      in 49 ALS patients classified according to the El Escorial criteria. Abnormal
      NAA/Cho ratios were detected in 53% of ALS patients. Abnormal TMS results (i.e.
      cortical inexcitability or prolonged CMCT's) were obtained in 63% of ALS
      patients. If one or both methods were considered for diagnosis of upper motor
      neuron degeneration/dysfunction, the percentage of abnormal findings was 77%,
      whilst in 39% of all patients both methods produced abnormal results. Compared to
      TMS, 1H-MRS detected more patients with upper motor neuron involvement in the
      suspected El Escorial subgroup (42% versus 25%), whereas TMS detected more
      patients with upper motor neuron involvement in the possible (81% versus 50%),
      probable (71% versus 57%) and definite El Escorial subgroup (71% versus 64%). We
      conclude that the combined use of 1H-MRS and TMS increases diagnostic accuracy
      for the detection of upper motor neuron involvement in ALS patients.

PMID- 11574103
TI  - Cerebrotendinous xanthomatosis: 11-year treatment with chenodeoxycholic acid in
      five patients. An electrophysiological study.
AB  - We report the electrophysiological follow-up of five cerebrotendinous
      xanthomatosis patients treated for 11 years with chenodeoxycholic acid (CDCA).
      Nerve conduction velocity (NCV) was reduced in three cases. P100 latency of
      visual evoked potentials was delayed in four cases, interpeaks I-III and I-V of
      brainstem auditory evoked potentials (BAEPs) was increased in two and interpeak
      N13-20 of upper limb somatosensory evoked potentials (SEPs) was slowed in one.
      After 4 months of therapy with CDCA, NCV was normal and did not show any
      significant change during the 11 years of observation. Central motor conduction
      time of motor evoked potentials (MEPs) and N24-P40 interpeak latency of lower
      limb SEPs were increased in five and four cases, respectively, in spite of 2/3
      year treatment with CDCA. Improvement of evoked potentials, especially of MEPs
      and SEPs, was slower and continued over the whole 11-year period. The size of
      xanthomas slightly decreased in some patients during treatment and the clinical
      manifestations stabilized, avoiding progressive worsening, but there was no
      significant improvement in neurological deficit. Two sisters of patients who
      never took CDCA showed progressive worsening of clinical manifestations, upper
      limb SEPs and BAEPs.

PMID- 11574104
TI  - Molecular analysis of SMN, NAIP and P44 genes of SMA patients and their families.
AB  - Mutations of the telomeric survival motor neuron gene (SMN1) are related to
      spinal muscular atrophy (SMA). However, no phenotype-genotype correlation has
      been observed since the SMN1 gene is lacking in the majority of patients affected
      with either the severe form (type I) or the milder forms (types II and III).
      Here, we analyze the SMN, NAIP and P44 genes in 132 Chinese SMA patients and
      their families. At least three types of normal allele, and four types of mutant
      allele were found in this study. The combination of one normal allele with one
      mutant allele resulted in carriers of different types, and the combination of
      different mutant alleles accounted for the different genotypes among different
      types of SMA. Deletions of mutant alleles can be further subgrouped into four
      types, which includes involving SMN1, SMN1 and NAIP(T) (telomeric portion of NAIP
      gene), SMN1 and NAIP(T) and P44(T) (telomeric portion of P44 gene), and SMN1 and
      SMN2 (centromeric portion of SMN gene). Some of the severe (type I) SMA cases
      correlated with the extent of deletions in the SMN, NAIP and P44 genes or the
      dosage of SMN gene when both SMN1 and SMN2 are deleted. We also found two novel
      point mutations, an A insertion at codon 8 (AGT-->AAGT) and an A substitution at
      codon 228 (TTA-->TAA).

PMID- 11574105
TI  - Temporal profile of anti-ganglioside antibodies and their relation to clinical
      parameters and treatment in Guillain-Barre syndrome.
AB  - Elevated anti-ganglioside antibody levels mainly of anti-GM1 and anti-GD1a
      specificities have been reported in THE serum of patients with Guillain-Barre
      syndrome (GBS). The relevance of anti-ganglioside antibodies other than anti-GM1
      and anti-GD1a IgG antibodies and the temporal profile of anti-ganglioside
      antibodies in GBS is less clear. We studied serum antibodies to GM1, GD1a, GD1b,
      GQ1b, sulfatide and cardiolipin of the IgM, IgG and IgA classes over the course
      of GBS in patients who were untreated or treated with high dose intravenous
      immunoglobulin (IvIg). Antibodies to GD1b, GQ1b, sulfatide and cardiolipin were
      not detected in the sera of the GBS patients examined in this study. Anti-GM1 IgG
      titers peaked around 40 days and anti-GD1a IgM around 90 days after GBS onset.
      Titers of anti-GM1 IgG antibodies decreased following IvIg treatment. Patients
      with antibody peaks, defined as fivefold or higher increase in antibody titer
      compared to the lowest antibody titer over the course of GBS, had higher
      disability scores during the first two weeks of GBS and a worse clinical outcome
      (anti-GM1 IgG and anti-GD1a IgM antibody peaks) and axonal damage (anti-GD1a IgM
      antibody peaks), compared to patients without peak antibody titers. Anti-GM1 IgG
      and anti-GD1a IgM antibodies are thus strongly associated with more severe- and
      predominantly axonal cases of GBS. The appearance of anti-GM1 IgG and anti-GD1a
      antibody peaks in the serum after the termination of the acute phase of GBS
      suggests that these antibodies are produced secondary to nerve damage in GBS. The
      data does not exclude the possibility that secondarily secreted anti-GM1 IgG and
      anti-GD1a IgM antibodies may themselves be biologically active and play a role in
      disease propagation and/or recovery from disease in some patients with GBS.

PMID- 11574106
TI  - Risk factors of Parkinson's disease in Indian patients.
AB  - Epidemiological data on risk factors of Parkinson's disease (PD) are not
      available from India. In a case control study, we investigated environmental and
      genetic risk factors in the etiology of idiopathic Parkinson's disease. Three
      hundred seventy-seven patients of Parkinson disease (301 men, 76 women, mean+/-SD
      age 56.78+/-11.08 years) and equal number of age matched (+/-3 years)
      neurological controls (271 men, 106 women, mean+/-SD age 56.62+/-11.17 years)
      were included in the study. Conditional logistic regression model was used to
      determine the risk factors of PD. We found that male gender, family history of
      Parkinson's disease, past history of depression of up to 10-year duration and
      well water drinking of more than 10-year duration were significantly associated
      with occurrence of Parkinson's disease, whereas tobacco smoking of up to 20-year
      duration and exposure to pets had protective effect. However, tobacco smoking of
      more than 20-year duration, well water drinking of up to 10-year duration,
      vegetarian dietary habit, occupation involving physical exertion, rural living,
      farming, exposure to insecticides, herbicides, rodenticides, alcohol intake and
      family history of neurodegenerative diseases had no significant correlation with
      occurrence of PD in the patient population studied. Results of our study support
      the hypothesis of multifactorial etiology of PD with environmental factors acting
      on a genetically susceptible host.

PMID- 11574107
TI  - Seizures in Japanese encephalitis.
AB  - OBJECTIVE: Although Japanese encephalitis (JE) has been reported to be associated
      with seizures, there is no report on its frequency, pattern and severity and
      their correlation with electroencephalography (EEG) and radiological findings. In
      this communication, the analysis of seizures in 65 JE patients seen during 1991
      1999 is presented. METHODS: The diagnosis of JE was based on clinical,
      radiological and serological criteria. The patients were subjected to a detailed
      clinical evaluation. Frequency and pattern of seizures and other neurological
      findings were recorded. Cranial CT scan or MRI was carried out in all the
      patients. Electroencephalograph was recorded using the 10-20 system of electrode
      placement. Patients' outcome was defined, on the basis of clinical status for 3
      months, into poor, partial and complete recovery. The relationship between
      seizures and other clinical, radiological and EEG parameters was evaluated by the
      Z test of proportion using the two-tail approach. RESULTS: The patient's age
      ranged between 2 and 57 years, 24 were females and 19 were below 13 years of age.
      Thirty patients had seizures within the first week of encephalitis. The seizures
      were generalised tonic-clonic in 17 patients and partial motor with secondary
      generalization in 13 patients. Eleven patients had a single seizure, 8 had two
      seizures and 11 had multiple seizures. Two patients were presented with status
      epilepticus. Interictal EEG in the patients with seizures revealed theta to delta
      slowing in all patients and epileptiform discharges in four patients only. MRI
      revealed thalamic lesions bilaterally in 24, cortical in 7, basal ganglia in 8
      and brainstem in 3 patients out of 26 patients with seizure. In the seizure
      group, three patients died, nine had poor, eight had partial and nine had
      complete recovery. Upon comparison of the JE patients with and without seizures,
      Glasgow coma scale (GCS) score, focal weakness, EEG slowing and cortical and
      thalamic lesion on CT or MRI were significantly related to the occurrence of the
      seizures; however, it was not associated with poor outcome. CONCLUSIONS: JE is
      associated with seizures in 46% of the patients in the acute stage of
      encephalitis which is easily controlled by monotherapy. Patients with severe
      encephalitis were associated with higher frequency of seizures.

PMID- 11574108
TI  - Impaired novelty P3 potentials in multiple system atrophy--correlation with
      orthostatic hypotension.
AB  - Although neuropsychological tests demonstrate frontal lobe dysfunction in
      multiple system atrophy (MSA), assessment of frontal function using event-related
      brain potentials (ERPs) has not been sufficiently performed in MSA. The
      correlation between frontal lobe dysfunction and orthostatic hypotension (OH),
      which is known to cause frontal hypoperfusion, remains unclear. Our objectives
      were to assess frontal lobe dysfunction in MSA patients using ERPs and to
      elucidate the relevance of OH to changes in ERPs. Nine consecutive patients with
      MSA and nine age- and gender-matched healthy controls were compared by
      performance in the Wisconsin Card Sorting Test (WCST) and somatosensory ERPs to
      target and novel stimuli, namely, parietal maximal P3 (target P3) and fronto
      central P3 (novelty P3), respectively. The correlation between novelty P3 and OH
      was evaluated in the MSA group. The MSA group showed a poorer performance in
      categories achieved (CA), total errors (TE) and perseverative errors by Nelson's
      (PEN) method in the WCST compared with the control group (CA and PEN: p<0.01; TE:
      p<0.02). Novelty and target P3s in the MSA group showed significantly prolonged
      latency (novelty: p<0.05; target: p<0.01) and reduced amplitude (novelty: p<0.02;
      target: p<0.01) compared with the control group. There was a significant negative
      correlation between novelty P3 latency and a drop in systolic blood pressure
      (r=0.76; p<0.02). Abnormalities of novelty P3 in the MSA group might reflect
      frontal lobe dysfunction, namely failure of attentional set-shifting, that was
      identified by the WCST. OH may play a role in the development of frontal lobe
      dysfunction in MSA.

PMID- 11574109
TI  - The -174/-597 promoter polymorphisms in the interleukin-6 gene are not associated
      with susceptibility to multiple sclerosis.
AB  - Interleukin-6 (IL-6) has been implicated in the etiology of experimental
      autoimmune encephalomyelitis (EAE) in transgenic animals and contributes to
      neuropathology in humans. A single nucleotide polymorphism (SNP) at position -174
      in the IL-6 gene promoter (IL-6pr) appears to influence IL-6 expression. Complete
      linkage disequilibrium was observed between the -174 and the -597 alleles. The
      aim of this study was to investigate the possible influence of -174/-597 IL-6pr
      polymorphisms on susceptibility to multiple sclerosis (MS). Genotyping of the 
      597 variant was performed by an RFLP method in 131 MS patients [88 relapsing
      remitting (RR-MS), 43 secondary progressive (SP-MS)] and 157 healthy subjects. No
      differences were found between MS patients and controls with respect to the
      distribution of -597 IL-6pr genotypes. Neither was found when genotypes were
      analyzed according to the clinical course of the disease (RR-MS or SP-MS). Future
      studies focusing on complex transcriptional interactions between the IL-6pr and
      3' flanking region polymorphic sites will be necessary to determine the IL-6
      haplotype influence on susceptibility to MS.

PMID- 11574110
TI  - A clinical study of patients with genetically confirmed Huntington's disease from
      India.
AB  - BACKGROUND: Clinical data across the globe especially in genetic diseases like
      Huntington's disease (HD) is most helpful when collected using standardized
      formats. This helps in proper comparison of clinical and genetic data. METHODS:
      Herein, we report clinical data on 26 genetically confirmed HD patients from 19
      Indian families predominantly from South India. Clinical data and evaluation was
      performed using standardized formats used by the Huntington Disease Study Group.
      RESULTS: Adult onset HD was commonest while Juvenile HD (onset <20 years) was
      observed in approximately 15% of patients. Chorea was the commonest presenting
      symptom (n=23, 88.5%) while remaining presented with psychiatric symptoms (n=3,
      11.5%). Impairment of saccades was observed in approximately 75% of patients.
      Mean (SD) CAG repeats in the abnormal allele was 48.4 (8.7). Total motor score
      but not the total behavioral score worsens with duration of symptoms. The
      functional checklist score correlates with total motor score rather than with
      duration of symptoms. CONCLUSIONS: We detail clinical characteristics in
      genetically confirmed HD patients from a predominantly South Indian cohort. We
      observed a slightly higher occurrence of Juvenile HD. Functional disabilities in
      our patients correlate with worsening of motor rather than behavioral symptoms.

PMID- 11574111
TI  - The inter- and intraobserver reliabilities of a new classification system for
      ischaemic stroke: the South London Stroke Register.
AB  - OBJECTIVES: This study aims to determine the inter- and intraobserver
      reliabilities of an aetiological classification devised as part of a community
      based stroke register. METHODS: Patients with first-ever acute ischaemic stroke
      were clinically assessed and received investigation according to a set protocol.
      Results of the clinical assessment and investigations were used to determine an
      aetiological stroke subtype for each patient by observer 1. Aetiological subtypes
      consisted of extracranial large artery atherosclerosis (LAAec), intracranial
      large artery atherosclerosis (LAAic), high-risk cardioembolism (CH), medium-risk
      cardioembolism (CM), small vessel occlusion (SVO), other aetiology (OTH), no
      aetiology identified (NA) and multiple probable or multiple possible aetiology
      (MPA). The same data were distributed to a further four observers along with the
      criteria for the classification system. Two of the observers were retested on the
      same patients after of period of 8 weeks. Inter- and intraobserver agreement was
      determined using the kappa statistic, which gives the chance-adjusted percentage
      agreement. RESULTS: Forty-five consecutive patients were included. The overall
      kappa statistic for ischaemic stroke was 0.91 indicating excellent agreement.
      Kappa statistics were highest for the more frequent subtypes of SVO (0.97) and CH
      (0.97). Substantially high kappa statistics were also obtained for the less
      frequent categories of LAAec (0.91), CM (0.84), NA (0.89) and MPA (0.87). A low
      kappa statistic was obtained for the category OTH (0.16), which had a low
      frequency of reporting, indicating poor agreement. The kappa statistic for
      probable categories was higher than the kappa statistic for all stroke subtypes
      at 0.96. Intraobserver agreement between first and second assignments of subtype
      diagnoses for both observers reached excellent agreement with kappa statistics of
      0.83 and 0.85. CONCLUSION: The aetiological classification system, designed for
      use in the investigation of the epidemiology, stroke subtype and their relation
      to the natural history of stroke in a multiethnic inner city population, allows
      high inter- and intrarater agreements of subtype diagnosis.

PMID- 11574112
TI  - Single cell analysis of CAG repeat in brains of dentatorubral-pallidoluysian
      atrophy (DRPLA).
AB  - Somatic mosaicism of an expanded repeat is present in tissues of patients with
      triplet repeat diseases. Of the spinocerebellar ataxias associated with triplet
      repeat expansion, the most prominent heterogeneity of the expanded repeat is seen
      in dentatorubral-pallidoluysian atrophy (DRPLA). The common feature of this
      somatic mosaicism is the difference in the repeat numbers found in the cerebellum
      as compared to other tissues. The expanded allele in the cerebellum shows a
      smaller degree of expansion. We previously showed by microdissection analysis
      that the expanded allele in the granular layer in DRPLA cerebellum has less
      expansion than expanded alleles in the molecular layer and white matter. Whether
      this feature of lesser expansion in granule cells is common to other types of
      neurons is yet to be clarified. We used a newly developed excimer laser
      microdissection system to analyze somatic mosaicism in the brains of two
      patients, one with early- and another with late-onset DRPLA, and used single cell
      PCR to observe the cell-to-cell differences in repeat numbers. In the late onset
      patient, repeat expansion was more prominent in Purkinje cells than in granule
      cells, but less than that in the glial cells. In the early onset patient, repeat
      expansion in Purkinje cells was greater than in granule cells but did not differ
      from that in glial cells. These findings suggest that there is a difference in
      repeat expansion among neuronal subgroups and that the number of cell division
      cycles is not the only determinant of somatic mosaicism.

PMID- 11574113
TI  - Recurrent jaw dislocation after botulinum toxin treatment for sialorrhoea in
      amyotrophic lateral sclerosis.
AB  - Botulinum toxin (BTX) has been used successfully to treat various movement
      disorders, and is increasingly used for many other medical conditions.
      Sialorrhoea is a disabling symptom in many neurological patients including those
      with Parkinson's disease, stroke and amyotrophic lateral sclerosis (ALS). BTX has
      recently been shown to be effective for treating sialorrhoea. We report an ALS
      patient who developed recurrent jaw dislocation following BTX treatment for
      sialorrhoea to highlight the observation that intraparotid BTX may be complicated
      by jaw dislocations in some at-risk ALS patients. Clinicians using BTX to treat
      sialorrhoea in ALS need to be aware of this potentially serious complication.

PMID- 11574114
TI  - A system for applying rapid warming or cooling stimuli to cells during patch
      clamp recording or ion imaging.
AB  - We describe a system for superfusing small groups of cells at a precisely
      controlled and rapidly adjustable local temperature. Before being applied to the
      cell or cells under study, solutions are heated or cooled in a chamber of small
      volume ( approximately 150 microl) and large surface area, sandwiched between
      four small Peltier elements. The current through the Peltier elements is
      controlled by a microprocessor using a PID (proportional-integral-derivative)
      feedback algorithm. The chamber can be heated to at least 60 degrees C and cooled
      to 0 degrees C, changing its temperature at a maximum rate of about 7 degrees C
      per second; temperature ramps can be followed under feedback control at up to 4
      degrees C per second. Temperature commands can be applied from the digital-to
      analogue converter of any laboratory interface or generated digitally by the
      microprocessor. The peak-to-peak noise contributed by the system does not exceed
      that contributed by a patch pipette, holder and headstage, making it suitable for
      single channel as well as whole cell recordings.

PMID- 11574115
TI  - Assessment of motor behavior using a video system and a clinical rating scale in
      parkinsonian monkeys lesioned by MPTP.
AB  - The best current model of Parkinson's disease is the primate treated with 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Quantification of animal
      movement is important for the study of severity of parkinsonian syndrome induced
      by MPTP and response to drug treatments. Both require clinical rating scales that
      measure motor behavior with well-defined objective items. However, evaluations
      using these scales depend on the observer scoring the different items, according
      to his/her experience. The video image analyzer system, which produces an
      activity curve in correlation with the visual study of animal motor behavior,
      offers an automatic evaluation method that is observer-independent and
      reproducible. Using such an system we defined items correlated with those used in
      clinical rating scales that are sensitive to animal motor changes, decrease in
      movements with MPTP intoxication and alleviation afforded by levodopa: global
      locomotor activity and specific activities (climbing, social interactions, eating
      and drinking behaviors).

PMID- 11574116
TI  - A novel fluorescent method for direct visualization of neurofibrillary pathology
      in Alzheimer's disease.
AB  - Methods currently available for detecting neurofibrillary pathology are indirect
      and depend on staining with exogenous chemicals or antibodies. In the present
      study, we report a novel method named intrinsic fluorescence induction (IFI),
      which allows direct visualization of neurofibrillary tangles (NFTs), neuropil
      threads (NTs), and neuritic plaques (NPs) in tissue sections of Alzheimer's
      disease (AD) brain. The IFI method is based on both induction of a red intrinsic
      fluorescence and quenching red background autofluorescence. The IFI procedure
      includes sustained hydrophobic treatment, protein secondary structure enhancement
      and incubation in high concentration of phosphate buffer. Following this
      procedure, a unique red fluorescence is generated from the structures of NFTs,
      NTs, and NPs in brain sections from AD patients. Sequential application of mild
      permanganate oxidation and 1% sodium borohydride selectively removes the red
      background autofluorescence, while the latter enhances the intrinsic fluorescence
      of neurofibrillary pathology. Comparative studies reveal that the IFI method is
      as sensitive as Gallyas silver staining, and more sensitive than Bielschowsky
      silver staining or PHF-1 immunostaining in detecting NFTs in the pre-alpha layer
      of entorhinal cortex and the pri-alpha layer of the entorhinal/transentorhinal
      cortex. Furthermore, the IFI method is sensitive in displaying plaque neurites
      and threads, but not NFTs in the hippocampus. This novel finding provides a
      direct method for detecting neurofibrillary pathology in particular regions of AD
      brain and a novel tool for AD research.

PMID- 11574117
TI  - Two-photon microscopy in brain tissue: parameters influencing the imaging depth.
AB  - Light scattering by tissue limits the imaging depth of two-photon microscopy and
      its use for functional brain imaging in vivo. We investigate the influence of
      scattering on both fluorescence excitation and collection, and identify tissue
      and instrument parameters that limit the imaging depth in the brain. (i) In brain
      slices, we measured that the scattering length at lambda=800 nm is a factor 2
      higher in juvenile cortical tissue (P14-P18) than in adult tissue (P90). (ii) In
      a detection geometry typical for in vivo imaging, we show that the collected
      fraction of fluorescence drops at large depths, and that it is proportional to
      the square of the effective angular acceptance of the detection optics. Matching
      the angular acceptance of the microscope to that of the objective lens can result
      in a gain of approximately 3 in collection efficiency at large depths (>500
      microm). A low-magnification (20x), high-numerical aperture objective (0.95)
      further increases fluorescence collection by a factor of approximately 10
      compared with a standard 60x-63x objective without compromising the resolution.
      This improvement should allow fluorescence measurements related to neuronal or
      vascular brain activity at >100 microm deeper than with standard objectives.

PMID- 11574118
TI  - Experimental glaucoma in the primate induced by latex microspheres.
AB  - The injection of sterile latex microspheres into the anterior chamber of the eye
      is presented as a simple and cost effective method for inducing chronic elevation
      of intraocular pressure (IOP) and experimental glaucoma in primates. The
      microspheres produce elevated IOP primarily by restricting the outflow of aqueous
      humor through the trabecular meshwork located in the chamber angle. Different
      levels and durations of elevated IOP can be obtained by altering the frequency
      and number of microspheres injected. In comparison with other primate models of
      experimental glaucoma, the approach described here has the advantages of
      producing chronic elevations of IOP without the need for expensive ophthalmic
      equipment and personnel, surgical intervention or intraocular inflammation, and
      without compromising visibility of the optic disc, which is necessary for
      clinical assessment of the onset and progression of the disease.

PMID- 11574119
TI  - Quantification of neural tissue injury in a rat radiculopathy model: comparison
      of local deformation, behavioral outcomes, and spinal cytokine mRNA for two
      surgeons.
AB  - Clinical and experimental work indicate that a variety of factors contribute to
      radicular pain mechanisms, including mechanical injury. While it has been
      qualitatively suggested that the magnitude of nerve root mechanical injury
      affects the nature of the pain response, no study has quantified the local in
      vivo injury biomechanics in these models. Therefore, it was the purpose of this
      study to develop and implement an in vivo method to quantify compressive nerve
      root injury strain severity and characterize its effect on the resulting
      responses in an existing lumbar radiculopathy rat model. Male Holtzman rats were
      divided into a sham group with only nerve root exposure or a ligation group with
      the nerve root tightly ligated using silk suture. Using image analysis, nerve
      root radial strains were calculated at the time of injury for two surgeons.
      Mechanical allodynia was continuously assessed throughout the study and spinal
      cord cytokine mRNA levels were assayed on postoperative day 7. The degree of
      intersurgeon variability for imposing a ligation injury in this model was also
      assessed. Mean compressive injury strains in the nerve root were 32.8+/-14.2% and
      were not different for the two experimenters. Animals undergoing more severe
      ligation strains exhibited significantly heightened allodynia following injury
      and greater upregulation of the inflammatory cytokines IL-1alpha/beta, IL-6, and
      IL-10. Results indicate a direct correlation of local nerve root injury severity
      with the ensuing physiologic responses associated with nociception.

PMID- 11574120
TI  - A sequential protocol combining dual neuroanatomical tract-tracing with the
      visualization of local circuit neurons within the striatum.
AB  - We describe here an experimental approach designed to aid in the identification
      of complex brain circuits within the rat corpus striatum. Our aim was to
      characterize in a single section (i) striatal thalamic afferents, (ii)
      striatopallidal projection neurons and (iii) striatal local circuit interneurons.
      To this end, we have combined anterograde tracing using biotinylated dextran
      amine and retrograde neuroanatomical tracing with Fluoro-Gold. This dual tracing
      protocol was further implemented with the visualization of different
      subpopulations of striatal interneurons. The subsequent use of three different
      peroxidase substrates enabled us to unequivocally detect structures that were
      labeled within a three-color paradigm.

PMID- 11574121
TI  - Early visual changes in reflected light on non-stained brain sections after focal
      ischemia mirror the area of ischemic damage.
AB  - There is no reliable, simple method for delineation of ischemic regions at early
      time points after ischemia. We propose that at early times after stroke, ischemic
      regions can be visualized as a subtle change in reflected light directly in thaw
      mounted, dried 20 microm brain sections. In 15 male Sprague-Dawley rats,
      anesthetized with isoflurane, middle cerebral artery transection and permanent
      bilateral common carotid artery occlusion was performed and brains were processed
      in five different ways. Areas of reflective change (RC) on non-stained sections
      were compared with areas on the adjacent sections delineated by microtubule
      associated protein 2 (MAP2) antibody, a reliable marker for early post-stroke, in
      five rats each at 1, 3, and 6 h after focal cerebral ischemia. A statistically
      significant correlation between ischemic areas (IA) measured on non-stained brain
      sections (IA(RC)) and adjacent sections immunostained (IM) with MAP2 Ab (IA(IM))
      (IA(RC)=0.05+0.88.IA(IM); R2=0.8; n=15; P<0.01) and a small mean difference +/-2
      S.D. (-0.9+/-6.0%) indicated that the area measured on non-stained sections
      reflects the IA measured on MAP2 -IM sections. At 1 and 3 h after ischemia, the
      ratio between ischemic regions measured on the non-stained sections and on the
      adjacent sections immunostained with MAP2 Ab were not different from 100% (97.6+/
      1.7%, 100.9+/-6.0%). At 6 h post-stroke, the IA measured on the non-stained
      sections was larger than on the IM sections (109.8+/-2.7%, P<0.01, compared to
      100% ratio). Our study demonstrated that this quick and simple method for
      detection of damaged brain permitted the use of brain tissue for other assays and
      could be very useful for neuroprotective evaluation and for directed micro
      sampling of brain tissue at early times after ischemia.

PMID- 11574122
TI  - The application of cross-point switch arrays as input selector switch devices for
      multi-channel electrophysiological experiments.
AB  - Integrated circuits (ICs) containing cross-point switch arrays were applied to
      create analog input selector switch devices for multi-channel
      electrophysiological experiments. The described analog input selector switch
      devices make it possible to connect to the main amplifier's inputs those
      microelectrode and preamplifier output wires that yield unit discharges of
      acceptable shape and amplitude, or yield other kind of acceptable
      electrophysiological signals (EEG, EP). This kind of selector allows to use
      higher number of preamplifier channels and to ignore the input channels without
      adequate signals or the channels with noisy inputs. No manual switching is
      required, as the work is done by computer controlled switches. The switch
      positions can be saved and reloaded at the next experimental session through an
      I/O port (e.g. the parallel port) of the computer.

PMID- 11574124
TI  - Progesterone and ovulation.
AB  - The role of progesterone (P) in the mechanism of ovulation is controversial at
      best. The contraceptive application of P was established in rodents in 1936 and
      with orally absorbed progestogenes was put to human use. There were hints on the
      proovulatory actions of P administered before the time of ovulation in rats by
      1948. Similarly, in 1954 the observation of high P level in the preovulatory
      follicle pointed to a role in ovulation. Neither of these two observations was
      further investigated and the positive feedback effect of P exerted on
      gonadotropins was described in 1968. Still the positive feedback between P and
      gonadotropins were not recognized as a physiologic mechanism, much less utilized
      pharmacologically. The apparent contradiction between these two different actions
      of P continues upto now. The paper sets out to expose this controversy and tries
      to resolve it using extensive literary data and the author's experiences with
      synthetic progestogenes in contraception, in the treatment of infertility and
      with the antigestagen mifepristone in blocking ovulation. The precise mechanisms
      lying behind these applications are explored and discussed in detail. The
      putative role of oestradiol (E2) in the mechanism of eliciting the gonadotropin
      surge is extensively discussed but refuted as the ovulatory signal. The time
      sequence between the rise of P and gonadotropins contradicts the common wisdom of
      LH causing luteinization. The positive feedback effect of P on the E2 sensitized
      ovulatory axis on the hypothalamic and pituitary level is discussed and its local
      role in the mechanism of follicular rupture is also taken into account. The final
      proof seems to be the antiovulatory effect of mifepristone, which blocked both
      GnRH pulsatility, pituitary sensitivity to GnRH and follicular rupture in several
      experiments. Thus, the dogma of LH peak causing follicular rupture and subsequent
      luteinization seems questionable, the putative role of E2 to initiate the
      ovulatory cascade has to be discarded and P's role as a trigger of the
      physiological mechanisms leading to ovulation should be firmly recognized.

PMID- 11574125
TI  - Effect of epidural analgesia on the fetal heart rate.
AB  - Fetal heart rate (FHR) changes occasionally follow the use of labor epidurals.
      Most studies of the phenomenon have focused on specific techniques, but similar
      timing and appearance suggest a common cause. Induction of analgesia may
      transiently alter the balance between factors encouraging and inhibiting uterine
      contractions with subsequent changes of FHR patterns. Regardless the etiology,
      these changes are transient and do not produce maternal or fetal morbidity.
      However, they must be promptly recognized and treated if necessary.

PMID- 11574126
TI  - Undernutrition during the first half of gestation increases the predominance of
      fetal tissue in late-gestation ovine placentomes.
AB  - OBJECTIVE: To investigate, in sheep, the effects of maternal undernutrition
      during the first half of pregnancy on placental growth and development and fetal
      growth. STUDY DESIGN: Six ewes (R) were subjected to a 15% reduction in nutrient
      intake for the first 70 days of gestation and thereafter received the recommended
      daily intake. Another group of six ewes (C) received the recommended daily intake
      throughout pregnancy. At 130 days gestation the ewes were killed and
      morphological and morphometrical measurements were carried out on the placenta
      and fetus. RESULTS: Undernutrition resulted in a significant alteration in
      placental morphology, which was seen as increased growth of the fetal side of the
      placenta in R animals. However, fetal size in late gestation was not affected by
      the undernutrition, suggesting that placental adaptation was successful in
      maintaining fetal growth. CONCLUSION: Placental adaptations, including changes in
      gross morphology, may preserve fetal growth if maternal undernutrition is not
      severe. The mechanisms remain to be elucidated.

PMID- 11574127
TI  - Bioelectrical impedance analysis during pregnancy and neonatal birth weight.
AB  - OBJECTIVE: To generate reference ranges for bioelectrical impedance indices
      throughout pregnancy and to investigate whether a relationship exists between
      these indices and the neonatal birth weight. STUDY DESIGN: Pregnant women with a
      singleton gestation, gestational age lower than 12 weeks, and absence of medical
      diseases before pregnancy were enrolled. Patients with pregnancy complications,
      such as hypertensive disorders, diabetes, and antiphospholipides syndrome were
      excluded. Antrophometric maternal parameters and bioelectrical impedance
      measurements were performed during the first, second, third trimester of
      pregnancy, at delivery and 60 days after delivery. Height(2)/resistance
      (cm(2)/Omega) and height(2)/reactance (cm(2)/Omega) were utilized to estimate the
      total and extracellular body water amounts, respectively. Spearman rank
      correlations and cox proportional hazard modelling were used for statistical
      purposes. RESULTS: 169 patients completed all measurements. Total and
      extracellular water amounts significantly increase as pregnancy advances and
      return to the pre-pregnancy values within 60 days after delivery. After
      adjustment for gestational age at delivery, fetal sex, and smoking habits,
      height(2)/resistance at 25 weeks (hazard=1.04, 95% confidence interval (CI) 1.02
      1.06, P<0.005), height(2)/resistance at 30 weeks (hazard=1.03, 95% CI 1.01-1.05,
      P<0.005), height(2)/reactance at 20 weeks (hazard=1.03,95% CI 1.01-1.05,
      P<0.005), and height(2)/reactance at 25 weeks (hazard=1.03, 95% CI 1.01-1.04,
      P<0.01) were found to be independent predictors of birth weight. CONCLUSION: We
      have provided reference ranges for bioimpedance analysis during pregnancy, an
      easy, fast and non invasive method to estimate the body water composition during
      pregnancy. Bioelectrical impedance indices during the second trimester of
      pregnancy are independently related to the birth weight.

PMID- 11574128
TI  - Treatment of preterm labor with the oxytocin antagonist atosiban: a double-blind,
      randomized, controlled comparison with salbutamol.
AB  - OBJECTIVE: To compare the efficacy and safety of atosiban and salbutamol in the
      treatment of preterm labor. STUDY DESIGN: A multicenter, double-blind, double
      placebo, randomized, controlled trial. Women (n=241) diagnosed with preterm labor
      at 23-33 gestational weeks were enrolled and received either atosiban (n=119) or
      salbutamol (n=122). At randomization, women were stratified by gestational age (<
      or =28 weeks and >28 weeks). Atosiban (i.v. bolus dose of 6.75 mg, then 300
      microg/min for 3h and 100 microg/min for up to 48h) and salbutamol (2.5-45
      microg/min) were administered by i.v. infusion for up to 48h. Retreatment with
      study drug or an alternative tocolytic agent was allowed. Main outcome measures
      included tocolytic effectiveness which was assessed in terms of the number of
      women undelivered after 48h and 7 days. Tocolytic efficacy and tolerability were
      assessed in terms of the proportion of women undelivered and who did not require
      alternative tocolytic therapy at 48h and 7 days of starting treatment. Safety was
      assessed in terms of maternal side effects and neonatal morbidity. RESULTS:
      Tocolytic effectiveness at 48h was 93.3 versus 95.0% (P=0.67) and after 7 days
      was 89.9 versus 90.1% (P=0.93) in the atosiban and salbutamol groups,
      respectively. Tocolytic efficacy and tolerability within 48h was 79.8 versus
      75.2% (P=0.15), and after 7 days was 58.8 versus 46.3% (P=0.021) in the atosiban
      and salbutamol groups, respectively. Maternal adverse events, including serious
      events, occurred more frequently in the salbutamol group. Neonatal outcomes were
      comparable between the study groups. CONCLUSIONS: The oxytocin antagonist
      atosiban was found to be better tolerated by both mother and fetus than
      salbutamol, with a comparable neonatal and infant safety profile, and atosiban
      was as effective as salbutamol in delaying threatened preterm birth. This study
      supports the clinical use of atosiban in the treatment of preterm labor.

PMID- 11574129
TI  - Planned vaginal delivery versus elective caesarean section in singleton term
      breech presentation: a study of 1116 cases.
AB  - OBJECTIVE: To compare neonatal and maternal morbidity and mortality between
      planned vaginal delivery and elective cesarean section for singleton term breech
      presentation. STUDY DESIGN: We studied retrospectively all deliveries of
      singleton breech presentations at term in the public Hospitals of Lyon between 1
      January 1991 and 31 December 1995. To take only the effect of delivery on the
      fetus into account, we eliminated high risk pregnancies and fetal malformations.
      Fetal parameters were corrected perinatal mortality, Apgar score<7 at 1 and 5
      min, umbilical cord arterial pH<7.15, neurological disorders, trauma and need for
      neonatal intensive care. Maternal parameters were mild, moderate and severe
      complications. RESULTS: Of the 1116 breech presentations, 702 (62.9%) underwent
      an elective caesarean section and 414 (37.1%) a planned vaginal delivery. In the
      latter group, 342 (30.6%) had a vaginal delivery and 72 (6.5%) a non-elective
      caesarean section. Infants for whom the vaginal route was planned were at higher
      risk of mortality and morbidity. There were 2 deaths in this group and none in
      the elective caesarean section group and all fetal parameters were poorer: more
      Apgar<7 at 5 min (RR: relative risk=3.05; 1.03-9.05), arterial pH<7.15 (RR=1.64;
      1.11-2.43), intubations (RR=7.35; 2.10-25.6), neurological disorders, trauma
      (RR=4.24; 1.66-10.8), transfer to intensive care units (RR=3.23; 1.57-6.64). The
      overall maternal morbidity was lower in the planned vaginal delivery group
      (RR=0.65; 0.44-0.94) but this was only because of less mild complications. The
      moderate and severe complications were the same in the two groups (RR=0.97; 0.59
      1.57). CONCLUSIONS: Planned vaginal delivery in singleton term breech
      presentation increases the risk of death and of neonatal complications. Elective
      caesarean section increases the risk of only mild maternal complications. For
      these reasons, elective caesarean section should be preferred for singleton term
      breech presentations.

PMID- 11574130
TI  - A high rate of epidural analgesia with bupivacaine-sufentanil is consistent with
      a low rate of caesarean section and instrumental deliveries.
AB  - OBJECTIVE: To prospectively evaluate if a high rate of epidural analgesia (EDA)
      with bupivacaine-sufentanil is consistent with a low rate of caesarean section,
      instrumental deliveries and dystocia and to evaluate maternal and fetal adverse
      effects of sufentanil. STUDY DESIGN: Populations-based prospective descriptive
      study. A change of EDA from bupivacaine to low dose bupivacaine-sufentanil at the
      delivery unit of the hospital during 1993 resulted in a marked increase in the
      rate of EDA. The outcome from the study period (1994-1995) was compared to the
      outcome during a reference period 1991-1992. RESULTS: There were no significant
      differences in the incidence of caesarean section and instrumental delivery for
      dystocia between the two periods (4.4 and 4.6%). The overall incidence of
      caesarean section, 9.6% and instrumental deliveries, 6.4% during the study period
      was lower than or comparable to the national background data (11.1 and 6.8%,
      respectively) while the EDA rate was markedly higher 37.8 versus 21.9%.
      CONCLUSION: A high rate of EDA, using low dose bupivacaine and sufentanil is
      consistent with a low rate of caesarean section and instrumental deliveries. No
      apparent negative effects on the neonates or mothers were observed.

PMID- 11574131
TI  - Using a new HPV detection system in epidemiological research: change of views on
      cervical dyskaryosis?
AB  - The prevalence of human papillomavirus (HPV) rises with increasing histological
      severity of neoplasia, more cigarettes smoked per day and higher lifetime number
      of sexual partners in women with cervical dyskaryosis. Recently, the highly
      sensitive SPF10 primers and Inno-LiPA (line probe assay) HPV prototype research
      assay became available for the detection and typing of HPV. BACKGROUND: using
      this system, we challenged the previously reported findings. STUDY DESIGN: the
      study group comprised 304 women referred because of abnormal pap smears in whom a
      histological diagnosis was made. Data on the lifetime number of sexual partners
      and smoking behaviour were obtained by questionnaire. HPV analysis was performed
      on cervical scrapes obtained at the enrollment visit. RESULTS: oncogenic HPV was
      found in 288 (95%) women. A total of 86 (30%) out of these 288 women disclosed
      multiple types. HPV 16 occurred significantly less often in multiple infections
      than was expected on the basis of chance alone. The grade of neoplasia was
      significantly associated with the presence of oncogenic HPV, and this association
      depended on the presence of HPV type 16. No association was found between grade
      of neoplasia and the presence of multiple HPV types. Neither the lifetime number
      of sexual partners nor smoking were associated with oncogenic HPV, the five most
      frequent HPV types separately or the presence of multiple types. CONCLUSION: we
      conclude that the association between the detection of HPV and the
      epidemiological risk factors, as found with the GP5/6 PCR in the past, could not
      be confirmed when using SPF10 PCR primers and LiPA HPV genotyping. We suggest
      that the number of sexual partners and smoking may be determinants of high HPV
      viral load rather than determinants of the presence of HPV per se.

PMID- 11574132
TI  - The feasibility of a one-stop colposcopy clinic in the management of women with
      low grade smear abnormalities: a prospective study.
AB  - OBJECTIVES: To assess the feasibility of a one-stop colposcopy clinic for the
      management of women with low-grade smear abnormalities. Secondly, to determine
      whether the approach of immediate information of biopsy results combined with
      treatment if indicated helps to reduce patient anxiety and improve overall
      patient satisfaction with the colposcopy process. DESIGN: Prospective study
      following the introduction of a "one-stop" process for the management of women
      with low grade smear abnormalities. SUBJECTS: First 118 women managed in a "one
      stop" clinic during an 8-month period. METHODS: Assessment of patient anxiety via
      self-completed questionnaires and comparison of anxiety scores with a control
      group managed via a standard clinic. RESULTS: The median waiting time for results
      in the one-stop clinic was 120 min (range: 100-165). All women in both groups
      felt anxious at the time of the clinic visit. However, after 1 week the majority
      of patients managed via the one-stop process felt slight anxiety only (P=0.0001)
      as opposed to those patients in the control group who remained anxious (P=NS). In
      addition, all women said they would prefer the one-stop approach for further
      smear abnormalities if a further colposcopic examination was warranted.
      CONCLUSION: A one-stop colposcopy clinic is feasible for the management of women
      with low-grade smear abnormalities. In addition, it delivers a quality service,
      optimises patient management, reduces anxiety and is the patient's choice.

PMID- 11574133
TI  - BCG vaccination to prevent implantation of endometriosis: an experimental study
      in rats.
AB  - To investigate whether BCG vaccination can prevent endometrial implantation in a
      rat model. Forty sexually mature virgin Wistar-Albino rats weighing 185-215g were
      randomly assigned (double-blind) to two groups. The first group (n=20) were
      injected with BCG 3 weeks before endometrial implantation to the eye. The second
      group (n=20) with BCG not injected before endometrial implantation was the
      control. Photobiomicroscopy observation was done weekly and 6 weeks post
      endometrial implantation all eyes were investigated histologically.Five implants
      grew in the anterior surface of the iris of the first (vaccinated) group and 17
      in the second (control) group. The difference was statistically significant.
      Systemic prophylaxis with BCG can exert an inhibitory effect on endometrial
      transplantation.

PMID- 11574134
TI  - Higher incidence of p53 mutation in cervical carcinomas with intermediate-risk
      HPV infection.
AB  - OBJECTIVE: Inactivation of p53, either through mutation or interaction with human
      papillomavirus (HPV) E6 oncoprotein, is a characteristic feature of cervical
      carcinoma cell lines that have been previously studied. To elucidate the role of
      p53 in the carcinogenesis of Korean cervical carcinomas, 27 HPV-positive and 13
      HPV-negative cervical carcinomas were studied in order to evaluate the status of
      the p53 gene. STUDY DESIGN: The HPV status was ascertained by polymerase chain
      reaction (PCR) amplification using consensus primers designed from the E6 and E7
      open reading frames (ORFs). The p53 mutation status was analyzed by direct
      sequencing of the PCR product in highly conserved exons 5-8. RESULTS: There was
      no significant difference in the frequency of the p53 mutation between the HPV
      positive and negative cases. All three mutations in the HPV-positive cases were
      associated with intermediate-risk viruses. The average age of the patients with
      the p53 mutation was 14 years older than that of patients without the p53
      mutation. CONCLUSION: p53 mutations are higher in the so called intermediate-risk
      HPV positive than HPV 16 or 18 positive cervical carcinomas.

PMID- 11574135
TI  - Survival analysis in familial ovarian cancer, a case control study.
AB  - OBJECTIVE: familial ovarian cancer patients have been found to differ from
      sporadic cases, clinically as well as in the molecular make-up of the tumour.
      Here, a case control study is performed to analyse potential differences in
      survival. STUDY DESIGN: 31 families with a strong history of ovarian and/or
      breast cancer presenting to a family cancer clinic 44 ovarian cancer patients
      were included. Each patient was matched for age and stage with controls from a
      cancer registry. Survival rates and the effect of several prognostic factors were
      analysed. RESULTS: median survival in the study group differed significantly from
      controls. A survival benefit for familial cases was maintained up to 5 years
      after diagnosis. Long-term survival was equally poor in both groups. CONCLUSION:
      the difference in survival between familial ovarian cancer cases and matched
      controls may reflect differences in biological behaviour. This may have important
      implications for the management and prevention of familial ovarian cancer.

PMID- 11574136
TI  - Serum erythropoietin levels in ovarian cancer patients receiving chemotherapy.
AB  - OBJECTIVE: To investigate the effects of repeated cis-dichlorodiamine-platinum
      (CDDP) exposure on serum erythropoietin (Epo) levels. STUDY DESIGN: In seven
      patients with ovarian cancer, Epo and haemoglobin concentration (c(Hb)) were
      measured before, 24h and 7 days after administration of the first three courses
      of chemotherapy. In seven control patients undergoing gynaecological surgery for
      non-malignant reasons, Epo and c(Hb) were measured before, 24h and 7 days after
      the operation. RESULTS: Following Epo increased, independent of concomitant
      anaemia, especially after the third course: 51mU/ml (S.D. 46) versus 122mU/ml
      (S.D. 83) (P=0.02). In the control patients, Epo was lower although the decrease
      of c(Hb) was significantly higher. CONCLUSION: Cis-platinum chemotherapy induces
      an increase in erythropoietin levels independent of anaemia. The underlying
      mechanism remains to be investigated.

PMID- 11574137
TI  - Vaginal, laparoscopic, or abdominal hysterectomies for benign disorders:
      immediate and early postoperative complications.
AB  - OBJECTIVE: hysterectomy for benign disorders is usually well tolerated, but
      complications do occur. The aim of this retrospective study is to document such
      complications. PATIENTS AND METHODS: between March 1991 and December 1998, 1604
      patients (mean age: 46 years) underwent hysterectomy for benign disorders.
      Peroperative and early postoperative complications were recorded for the 1248
      vaginal hysterectomies (8%), 190 laparoscopically assisted vaginal hysterectomies
      (12%), and 166 abdominal hysterectomies (10%). RESULTS: none of the patients
      died. There were 15 bladder (0.9%) and one ureter injury (0.06%) with no
      significant difference between routes. Intestinal injuries (0.6%) overall were
      more common when laparotomy was performed (2.4%). In 45 patients (2.8%), bleeding
      exceeded 500 ml. The rates were vaginal hysterectomy (2%, P<0.001), laparotomy
      (6.7%), and laparoscopy (5.3%). The overall reoperation rate of 0.8% does not
      differ with the type of the procedure. CONCLUSION: Per and early postoperative
      complications after hysterectomy remain important and patients should be aware of
      them. In order to control complications and decrease the morbidity, a high-risk
      population should be defined based on the patients' history of pelvic surgery and
      endometriosis, on their parity and the size of their uterus. For these patients,
      the most appropriate route should be preferred and complications should be
      assessed using different tests and subsequently treated during the same
      procedure.

PMID- 11574138
TI  - Case report of serous ovarian tumor of borderline malignancy (Stage Ic) in a
      pregnant woman.
AB  - We encountered a case of Stage Ic ovarian serous borderline malignancy in the
      first trimester of pregnancy. At laparotomy, spontaneous rupture of the capsule
      and a small amount of serous ascites was observed. Because of the laparotomy
      during pregnancy, correct staging of the tumor might not be performed. This case
      presented a major problem in deciding the treatment strategy, which are reported
      here together with some discussion of the literature on the preservation of
      fertility in borderline ovarian malignancy.

PMID- 11574139
TI  - Menorrhagia and adenomyosis in a patient with hyperhomocysteinemia, recurrent
      pelvic vein thromboses and extensive uterine collateral circulation treatment by
      supracervical hysterectomy.
AB  - A 37-year-old patient had recurring thromboses, occlusion of the left femoral
      vein with hereditary hyperhomocysteinemia, hypermenorrhea and anaemia.
      Conservative therapy with endometrium ablation and gestagene failed. A
      supracervical hysterectomy was done to preserve the presacral and left lateral,
      dorsal and caudal collaterals beside the uterus, and prevent a postoperative
      congestion, especially of the left leg.

PMID- 11574140
TI  - Laparoscopic vaginoplasty: using a sliding peritoneal flap for correction of
      complete vaginal agenesis.
AB  - In this technique of peritoneal neo-vaginoplasty, the recto-vesical space is
      dissected through the vulva under synchronous laparoscopic monitoring. Then the
      cranial limit of the pelvic peritoneum is incised circumferentially by
      laparoscopic approach and the two circular edges sutured sequentially. The
      isolated pelvic peritoneal sleeve is opened inferiorly and sutured to introital
      mucosal flaps.

PMID- 11574141
TI  - Restoration of menstruation after chemotherapy-induced amenorrhoea in a patient
      with ovarian immature teratoma.
AB  - We described a rare case of a 20-year-old woman with an ovarian immature teratoma
      who resumed regular spontaneous menses after more than 5 years of chemotherapy
      induced amenorrhoea. Efforts to reverse chemotherapy-induced ovarian failure can
      be continued even after persistent menstrual dysfunction of 5 or more years.

PMID- 11574142
TI  - Cervico-isthmic pregnancy: an extremely rare case diagnosed during labour.
AB  - This case report describes a cervico-isthmic pregnancy ending in a live vaginal
      birth at 37+2 weeks' gestation. The case remained undiagnosed throughout
      pregnancy when after a fairly normal labour a massive haemorrhage occurred. After
      an unsuccessful effort to control the bleeding conservatively, a total abdominal
      hysterectomy was carried out. During the operation the diagnosis of cervico
      isthmic pregnancy was confirmed, which was in accordance with the pathology
      report.

PMID- 11574143
TI  - Post-hysterectomy fallopian tube prolapse.
AB  - Post-hysterectomy fallopian tube prolapse is a rare complication with only 80
      cases described since 1902. Symptoms are non-specific and often of delayed onset.
      Final diagnosis is confirmed by vaginal biopsy with salpingectomy being the
      treatment of choice, preferably performed laparoscopically. Following surgery,
      complete symptom resolution is usually observed and no recurrence has been
      reported.

PMID- 11574144
TI  - Torsion of a nongravid uterus: an unexpected complication of an ovarian cyst.
AB  - Torsion of nongravid uterus is rare. Most reports occur during pregnancy. A case
      related to an adnexal mass, is described and the existing literature is reviewed.

PMID- 11574145
TI  - Port-site recurrence following laparoscopic para-aortic lymphadenectomy for
      squamous carcinoma of the cervix.
AB  - A port site tumour recurrence (PSR) followed laparoscopic para-aortic
      lymphadenectomy in a 46-year-old woman with stage IIb squamous carcinoma of the
      cervix. It occurred at the site used for removal of affected lymph nodes 7 months
      after surgery and completion of radiation and chemotherapy. It was associated
      with an increase in the size of tumour.

PMID- 11574147
TI  - The prion gene complex encoding PrP(C) and Doppel: insights from mutational
      analysis.
AB  - The prion protein gene, Prnp, encodes PrP(Sc), the major structural component of
      prions, infectious pathogens causing a number of disorders including scrapie and
      bovine spongiform encephalopathy (or BSE). Missense mutations in the human Prnp
      gene cause inherited prion diseases such as familial Creutzfeldt-Jakob disease.
      In uninfected animals Prnp encodes a glycophosphatidylinositol (GPI)-anchored
      protein denoted PrP(C) and in prion infections PrP(C) is converted to PrP(Sc) by
      templated refolding. Though Prnp is conserved in mammalian species, attempts to
      verify interactions of putative PrP binding proteins by genetic means have proven
      frustrating and the ZrchI and Npu lines of Prnp gene-ablated mice (Prnp(0/0)
      mice) lacking PrP(C) remain healthy throughout development. This indicates that
      PrP(C) serves a function that is not apparent in a laboratory setting or that
      other molecules have overlapping functions. Current possibilities involve
      shuttling or sequestration of synaptic Cu(II) via binding to N-terminal
      octapeptide residues and/or signal transduction involving the fyn kinase. A new
      point of entry into the issue of prion protein function has emerged from
      identification of a paralogue, Prnd, with 24% coding sequence identity to Prnp.
      Prnd lies downstream of Prnp and encodes the doppel (Dpl) protein. Like PrP(C),
      Dpl is presented on the cell surface via a GPI anchor and has three alpha
      helices: however, it lacks the conformationally plastic and octapeptide repeat
      domains present in its well-known relative. Interestingly, Dpl is overexpressed
      in the Ngsk and Rcm0 lines of Prnp(0/0) mice via intergenic splicing events.
      These lines of Prnp(0/0) mice exhibit ataxia and apoptosis of cerebellar cells,
      indicating that ectopic synthesis of Dpl protein is toxic to central nervous
      system neurons: this inference has now been confirmed by the construction of
      transgenic mice expressing Dpl under the direct control of the PrP promoter.
      Remarkably, Dpl-programmed ataxia is rescued by wild-type Prnp transgenes. The
      interaction between the Prnp and Prnd genes in mouse cerebellar neurons may have
      a physical correlate in competition between Dpl and PrP(C) within a common
      biochemical pathway that when mis-regulated leads to apoptosis.

PMID- 11574148
TI  - Molecular biology of the chromo domain: an ancient chromatin module comes of age.
AB  - The chromo domain motif is found in proteins from fungi, protists, plants, fish,
      insects, amphibians, birds, and mammals. The chromo domain peptide fold may have
      its origins as a chromosomal protein in a common ancestor of archea and
      eukaryota, making it a particularly ancient protein structural module. Chromo
      domains have been found in single or multiple copies in proteins with diverse
      structures and activities, most or all of which are connected with chromosome
      structure/function. In this review, our current knowledge of chromo domain
      properties is summarized and a variety of contexts in which chromo domains
      participate in aspects of chromatin metabolism are discussed.

PMID- 11574150
TI  - Cloning and characterization of the gene encoding human NPL4, a protein
      interacting with the ubiquitin fusion-degradation protein (UFD1L).
AB  - The ubiquitin fusion-degradation gene (UFD1L) encodes the human homologue of the
      yeast ubiquitin fusion-degradation 1 protein, an essential component of the
      ubiquitin-dependent proteolytic turnover and mRNA processing. Although the UFD1L
      gene has been mapped in the region commonly deleted in patients with DiGeorge
      syndrome (DGS)/velocardiofacial syndrome (VCFS), correlation between its
      haploinsufficiency and the phenotype has not yet been established. The only
      functional data available about mammalian Ufd1p is the ability to form a complex
      with the rat Npl4 protein, a component of the nuclear pore complex. In this paper
      we report the cloning and molecular characterization of the human NPL4 gene. This
      gene encodes for a protein 96% homologous to the rat Npl4, and 44 and 34%
      homologous to the C. elegans and S. cerevisiae Npl4 gene products, respectively.
      Fluorescence in situ hybridization experiments on human metaphases localized the
      NPL4 gene on the most telomeric region of chromosome 17q. Northern blots analysis
      on foetal and adult human tissues revealed a major approximately 4.5 kb
      transcript most abundant in heart, brain, kidney and skeletal muscle. In order to
      test a potential relationship between nuclear transport defects and some aspect
      of the DGS/VCFS phenotype, we also exclude the presence of mutations in the NPL4
      coding sequence in a subset of patients with DGS/VCFS and no detectable 22q11
      deletion or mutations at the UFD1L locus.

PMID- 11574149
TI  - Assignment of 118 novel cDNAs of cynomolgus monkey brain to human chromosomes.
AB  - In order to isolate genes that may not be represented in current human brain cDNA
      libraries, we have sequenced about 20,000 sequence tags of cDNA clones derived
      from cerebellum and parietal lobe of cynomolgus monkeys (Macaca fascicularis). We
      determined the entire cDNA sequence of approximately 700 clones whose 5'-terminal
      sequences showed no homology to annotated putative genes or expressed sequence
      tags in current databases of genetic information. From this, 118 clones with
      sequences encoding novel open reading frames of more than 100 amino acid residues
      were selected for further analysis. To localize the genes corresponding to these
      118 newly identified cDNA clones on human chromosomes, we performed a homology
      search using the human genome sequence and fluorescent in situ hybridization. In
      total, 108 of 118 clones were successfully assigned to specific regions of human
      chromosomes. This result demonstrates that genes expressed in cynomolgus monkey
      are highly conserved throughout primate evolution, and that virtually all had
      human homologs. Furthermore, we will be able to discover novel human genes in the
      human genome using monkey homologs as probes.

PMID- 11574151
TI  - A novel zebrafish bHLH gene, neurogenin3, is expressed in the hypothalamus.
AB  - Many basic helix-loop-helix transcriptional factors play important roles in
      vertebrate neurogenesis. Among them, Neurogenins act as determination factors and
      initiate the expression of differentiation genes such as neuroD and other
      neurogenic genes. Here we describe a zebrafish cDNA (neurogenin3 or ngn3)
      encoding a novel member of the Neurogenin family closest to mouse Ngn3 and human
      NGN3. Using a zebrafish radiation hybrid panel, ngn3 was mapped to zebrafish
      linkage group 13 and the region displayed a conserved synteny with the region of
      human chromosome 10 containing NGN3. As judged by RT-PCR and whole-mount in situ
      hybridization, ngn3 expression in zebrafish started much later than other
      neurogenin genes, at only around 24 h post-fertilization (hpf) and with a higher
      level of expression on the left side of the anterio-ventral diencephalon. Later
      at 48 hpf, ngn3 expression was detected in a small number of cells in the tuberal
      hypothalamus. Unlike Ngn3 in the mouse, zebrafish ngn3 mRNAs were not detected in
      developing pancreas and spinal cord. Genomic Southern blot hybridization
      suggested that a closely related sequence is present in the zebrafish genome and
      the hypothetical gene might result from the recent genome duplication in certain
      teleost lineage and share the function of the common ancestor with the currently
      characterized ngn3.

PMID- 11574152
TI  - Characterization of Spiroplasma citri adhesion related protein SARP1, which
      contains a domain of a novel family designated sarpin.
AB  - Transmission of the plant pathogen Spiroplasma citri by its leafhopper vector,
      Circulifer tenellus, involves adherence to and invasion of insect host cells. The
      S. citri adhesion related protein P89 (SARP1) was purified by immunoprecipitation
      using anti-SARP1 monoclonal antibodies. The protein's N-terminal amino acid
      sequence was determined and used to design a degenerate oligonucleotide. The
      labeled oligonucleotide hybridized to a 3.5 kb MboI fragment from S. citri DNA,
      which was then cloned and sequenced. Additionally, a 1.9 kb RsaI fragment of S.
      citri DNA, partially overlapping the MboI fragment, was isolated and
      characterized. Sequence analysis of the two clones revealed four open reading
      frames. ORF1 (675 bp) encodes the C-terminal part of a Soj-like protein. ORFs 1
      and 2 were separated from ORFs 3 and 4 by a putative transcription termination
      site, indicated by a hairpin structure. ORF3 encodes an amphiphilic 798 amino
      acid long protein with a cleavable signal peptide and a predicted transmembrane
      helix near the C-terminus. The mature protein of 85.96 kDa has a calculated pI
      value of 5.5 and has an N-terminal amino acid sequence consistent with that
      determined from the purified SARP1. At the N-terminus of this protein is a region
      consisting of six repeats, each 39-42 amino acids, a motif belonging to a
      previously unrecognized family of repeats found in a variety of bacterial
      proteins. The taxonomically spotty presence of this 'sarpin' domain and the
      relationship of the repeats to each other suggests a convergent evolution in
      multiple lineages.

PMID- 11574153
TI  - Using PAC nested deletions to order contigs and microsatellite markers at the
      high repetitive sequence containing Npr3 gene locus.
AB  - Highly polymorphic di- and tetranucleotide repeats in and around Npr3, a
      potential candidate gene for hypertension, have been identified using a novel
      approach. Because this chromosomal site is rich in repetitive DNA and difficult
      to sequence, P1 artificial chromosomes were retrofitted with a loxP transposon to
      map the gene sequence within a clone using a series of nested deletions.
      Sequences from ends of deletions 1-3 kb apart identified a (CA)(20) and a
      (TA)(18)-(CA)(8) repeat 8 kb upstream and within an intron of Npr3, respectively.
      DNA from 17 individuals was analyzed for length polymorphisms in these and eight
      additional repeats identified in 200 kb of working draft sequence from this
      region in GenBank. The sequence contigs and microsatellite repeats from GenBank
      were ordered using the P1-derived artificial chromosome deletion series. Several
      of these repeats were found to vary considerably in length in the set of genomic
      DNA tested. Since this site in chromosome 5p has recently been implicated in
      disease in studies with genetically hypertensive rats, the microsatellite markers
      reported here will be useful for genetic analysis and may even be implicated in
      the disease process in humans. We discuss how these types of data are useful for
      interpreting draft DNA sequence coming out of the genome projects, and the
      utility of deletion clones as a resource for ordering contigs and gap filling.

PMID- 11574154
TI  - Human cell lines expressing hormone regulated T7 RNA polymerase localized at
      distinct intranuclear sites.
AB  - Although several systems are now available for the controlled expression of
      eukaryotic genes transcribed by RNA polymerase II, regulated expression has been
      more difficult to achieve in the case of genes transcribed by RNA polymerase III.
      In the present study the gene for bacteriophage T7 RNA polymerase, implanted with
      a eukaryotic nuclear localization signal, was linked to a 5'-flanking ecdysone
      responsive promoter and stably transformed human cell lines were constructed in
      which the ecdysone promoter-T7 RNA polymerase gene had been integrated intact, as
      demonstrated by a polymerase chain reaction assay. Exposure of these cells to the
      ecdysone analog ponasterone A resulted in the appearance of a single protein
      having the expected size of T7 RNA polymerase in immunoblots of cell extracts
      probed with an affinity purified antibody raised against the C-terminus of T7 RNA
      polymerase. The induced T7 RNA polymerase was exclusively localized in the
      nucleus of induced cells and was undetectable in uninduced cells either by
      immunoblotting or immunofluorescence. The induced T7 RNA polymerase was present
      at numerous punctate foci dispersed throughout the nucleoplasmic regions of the
      nucleus and was also present in the nucleoli. Both of these observed intranuclear
      localizations have relevance to the potential applications of this system.

PMID- 11574155
TI  - Discovery and mapping of ten novel G protein-coupled receptor genes.
AB  - We report the identification, cloning and tissue distributions of ten novel human
      genes encoding G protein-coupled receptors (GPCRs) GPR78, GPR80, GPR81, GPR82,
      GPR93, GPR94, GPR95, GPR101, GPR102, GPR103 and a pseudogene, psi GPR79. Each
      novel orphan GPCR (oGPCR) gene was discovered using customized searches of the
      GenBank high-throughput genomic sequences database with previously known GPCR
      encoding sequences. The expressed genes can now be used in assays to determine
      endogenous and pharmacological ligands. GPR78 shared highest identity with the
      oGPCR gene GPR26 (56% identity in the transmembrane (TM) regions). psi GPR79
      shared highest sequence identity with the P2Y(2) gene and contained a frame-shift
      truncating the encoded receptor in TM5, demonstrating a pseudogene. GPR80 shared
      highest identity with the P2Y(1) gene (45% in the TM regions), while GPR81, GPR82
      and GPR93 shared TM identities with the oGPCR genes HM74 (70%), GPR17 (30%) and
      P2Y(5) (40%), respectively. Two other novel GPCR genes, GPR94 and GPR95, encoded
      a subfamily with the genes encoding the UDP-glucose and P2Y(12) receptors
      (sharing >50% identities in the TM regions). GPR101 demonstrated only distant
      identities with other GPCR genes and GPR102 shared identities with GPR57, GPR58
      and PNR (35-42% in the TM regions). GPR103 shared identities with the
      neuropeptide FF 2, neuropeptide Y2 and galanin GalR1 receptors (34-38% in the TM
      regions). Northern analyses revealed GPR78 mRNA expression in the pituitary and
      placenta and GPR81 expression in the pituitary. A search of the GenBank databases
      with the GPR82 sequence retrieved an identical sequence in an expressed sequence
      tag (EST) partially encoding GPR82 from human colonic tissue. The GPR93 sequence
      retrieved an identical, human EST sequence from human primary tonsil B-cells and
      an EST partially encoding mouse GPR93 from small intestinal tissue. GPR94 was
      expressed in the frontal cortex, caudate putamen and thalamus of brain while
      GPR95 was expressed in the human prostate and rat stomach and fetal tissues.
      GPR101 revealed mRNA transcripts in caudate putamen and hypothalamus. GPR103 mRNA
      signals were detected in the cortex, pituitary, thalamus, hypothalamus, basal
      forebrain, midbrain and pons.

PMID- 11574156
TI  - Cloning and characterization of human cathepsin L promoter.
AB  - Cathepsin L is a lysosomal cysteine protease, which is over-expressed and
      secreted by malignant cells. It is very potent in degrading collagen, elastin,
      laminin and other components of the basement membrane and, therefore, has been
      implicated in tumor invasion and metastasis. The structural portion of the human
      cathepsin L (hCATL) gene was cloned to elucidate its genomic organization
      (Chauhan et al., J. Biol. Chem. 218 (1993) 1039). In the present study, a 1.90 kb
      DNA fragment, containing 1825 bp of the 5' upstream region of hCATL and 75 bases
      of the first exon of the hCATL, was amplified by PCR from an adaptor ligated
      placental genomic library. This fragment has been demonstrated to exhibit
      promoter activity by luciferase reporter assays. Sequence analysis of this
      fragment revealed the presence of approximately 29 different putative
      transcription factor binding sites. Several of them like AP-4, GATA-1, Lmo2,
      CEBPB, MZF-1, NF-AT, etc. were present more than once in this region. However, a
      consensus CAAT box but no consensus TATA box was found within the 1.0 kb upstream
      of exon 1. The transcription initiation site of hCATL, using placental total RNA,
      was mapped to a single adenine residue 289 bases upstream of the ATG codon.

PMID- 11574157
TI  - Human monocyte x mouse melanoma fusion hybrids express human gene.
AB  - Artificial fusion of human monocyte with Cloudman S91 mouse melanoma cells
      resulted in hybrids that showed increased motility in vitro, enhanced metastatic
      potential in vivo, and also tended to be super melanotic (Rachkovsky et al.,
      Clin. Exp. Metastasis 16 (1998) 299). However, no gene derived from monocytes has
      been shown to be expressed in these hybrids until now. Similar observations have
      also been noted in hybrids originating from mouse macrophage and mouse melanoma
      cells. Having the advantage of species differences in mouse x human hybrids, we
      are able, this time, to show by RT-PCR that some genes specific to the human
      genome are expressed in these hybrids, indicating that not only is the genomic
      DNA from parental monocytes integrated in the hybrids but also some genes are
      being expressed. This observation may lead us to find contributory genes from
      monocyte and/or macrophage that are responsible for modulating the genotypes and
      hence the phenotypes in the hybrids.

PMID- 11574158
TI  - Cloning and analysis of mold-specific genes in the dimorphic fungus Histoplasma
      capsulatum.
AB  - A critical feature in the pathogenesis of the respiratory pathogen Histoplasma
      capsulatum is the conversion from the mold form (found in soil) to the yeast form
      in the lungs of the host. Little is known about the molecular biology of
      Histoplasma dimorphism. In particular, the possible roles of genes which are
      transcriptionally silent in yeast (i.e. mold-specific) have not been studied. We
      have produced a cDNA library highly enriched for mold-upregulated clones by
      fragmenting cDNA and removing yeast-specific and common sequences with a highly
      efficient enzyme degrading subtraction method. Screening of randomly selected
      clones identified cDNA fragments representing 16 different mold-upregulated
      genes. Because multiple cDNA fragments can be treated as alleles in a genetic
      screen, we were able to apply probability analysis to estimate the total number
      of mold-upregulated genes. We estimate that there are 27 upregulated genes; cDNA
      fragments of 16 have been isolated. Here we report the first isolation and
      analysis of cDNA from two mold-specific genes, MS8 (GenBank AF292398) and MS88
      (GenBank AF357882). The MS8 transcript was very strongly expressed in mold but
      not detected on Northern blots with yeast RNA. The putative MS8 protein was
      predicted to be 21.3 kDa (203 aa), very rich in glutamine and glycine and had a
      calculated pI of 6.76. The MS88 transcript was weakly expressed in mold and not
      detected in yeast. The putative MS88 protein was predicted to be 22.5 kDa (219
      aa) with a pI of 4.46. GenBank similarity searches revealed that the putative MS8
      protein was similar to a glutamine-rich protein, of unknown function, from the
      fungus Colletotrichum gloeosporioides (GenBank U94186). No significant matches
      were found for the putative MS88 protein.

PMID- 11574159
TI  - Targeted expression of a synthetic codon optimized gene, encoding the spruce
      budworm antifreeze protein, leads to accumulation of antifreeze activity in the
      apoplasts of transgenic tobacco.
AB  - A synthetic gene based on the primary sequence of the mature spruce budworm
      antifreeze protein (sbwAFP) was constructed by primer overlap extension. The
      amino acid codons were chosen to mimic those of a highly expressed tobacco
      nuclear gene. A DNA sequence encoding the amino-terminal leader sequence from the
      tobacco pathogen related protein 1b (PR), which targets the protein to the
      apoplastic space, was fused in frame to the synthetic sbwAFP gene. This fusion
      was placed downstream of the cauliflower mosaic virus 35S promoter and upstream
      of the nopaline synthase terminator in a T-DNA binary vector. Transgenic tobacco
      lines transcribing PR-sbwAFP were selected by RT-PCR. The apoplastic protein
      fractions of sbwAFP expressing tobacco lines exhibited enhanced antifreeze
      activity as demonstrated by the ability to inhibit ice re-crystallization and
      increased thermal hysteresis.

PMID- 11574161
TI  - The Candida albicans gene encoding the cytoplasmic leucyl-tRNA synthetase:
      implications for the evolution of CUG codon reassignment.
AB  - In a number of Candida species the 'universal' leucine codon CUG is decoded as
      serine. To help understand the evolution of such a codon reassignment we have
      analyzed the Candida albicans leucyl-tRNA synthetase (CaLeuRS) gene (CaCDC60).
      The predicted CaLeuRS sequence shows a significant level of amino acid identity
      to LeuRS from other organisms. A mitochondrial LeuRS (ScNAM2) homologue, which
      shared low identity with the CaLeuRS, was also identified in C. albicans.
      Antigenically-related LeuRSs were identified in a range of Candida species
      decoding the CUG codon as both serine and leucine, using an antibody raised
      against the N-terminal 15 amino acids of the CaLeuRS. Complementation experiments
      demonstrated that the CaLeuRS was able to functionally complement a Saccharomyces
      cerevisiae cdc60::kanMX null mutation. We conclude that there is no alteration in
      tRNA recognition and aminoacylation by the C. albicans LeuRS, which argues
      against it having a role in codon reassignment. The nucleotide sequences of the
      CaCDC60 and CaNAM2 genes were deposited at GenBank under Accession numbers
      AF293346 and AF352020, respectively.

PMID- 11574160
TI  - Characterization and comparative analysis of the EGLN gene family.
AB  - Rat Sm-20 is a homologue of the Caenorhabditis elegans gene egl-9 and has been
      implicated in the regulation of growth, differentiation and apoptosis in muscle
      and nerve cells. Null mutants in egl-9 result in a complete tolerance to an
      otherwise lethal toxin produced by Pseudomonas aeruginosa. This study describes
      the conserved Egl-Nine (EGLN) gene family of which rat SM-20 and C. elegans Egl-9
      are members and characterizes the mouse and human homologues. Each of the human
      genes (EGLN1, EGLN2 and EGLN3) are of a conserved genomic structure consisting of
      five coding exons. Phylogenetic analysis and domain organization show that EGLN1
      represents the ancestral form of the gene family and that EGLN3 is the human
      orthologue of rat Sm-20. The previously observed mitochondrial targeting of rat
      SM-20 is unlikely to be a general feature of the protein family and may be a
      feature specific to rats. An EGLN gene is unexpectedly found in the genome of P.
      aeruginosa, a bacterium known to produce a toxin that acts through the Egl-9
      protein. The pathogenic bacterium Vibrio cholerae is also shown to have an EGLN
      gene suggesting that it is an important pathogenicity factor. These results
      provide new insights into host-pathogen interactions and a basis for further
      functional characterization of the gene family and resolve discrepancies in
      annotation between gene family members.

PMID- 11574162
TI  - Identification of myosin II kinase from sea urchin eggs as protein kinase CK2.
AB  - Here we purified and identified a myosin II kinase from sea urchin eggs. The
      activity of this myosin II kinase in the egg extract was not significantly
      affected by Ca(2+)/calmodulin (CaM). Using sequential column chromatographies, we
      purified the myosin II kinase from the egg extract as a complex composed of 36-
      (p36) and 28-kDa (p28) proteins. Partial amino acid sequences of these two
      components were highly coincident with those of the alpha and beta subunits of
      protein kinase CK2 (formerly casein kinase II) in sea urchin eggs, respectively.
      To confirm that the purified myosin II kinase was CK2, we obtained a cDNA which
      encodes p36 from a cDNA library of sea urchin eggs. The amino acid sequence
      derived from the obtained cDNA showed over 70% homology to CK2 from various
      eukaryotes. Furthermore, recombinant p36, as well as the purified myosin II
      kinase, phosphorylated MRLC. One dimensional phosphopeptide mapping revealed that
      the phosphorylation site(s) of MRLC by both recombinant p36 and the purified
      myosin II kinase was identical. These clearly showed that the Ca(2+)/CaM
      independent myosin II kinase activity in sea urchin eggs was identical to CK2.

PMID- 11574163
TI  - Molecular cloning, sequence and expression of follicle-stimulating hormone
      receptor in the lizard Podarcis sicula.
AB  - The present paper reports the full nucleotide sequence of a cloned cDNA prepared
      from RNA of lizard ovaries. The open reading frame consists of 2019 nucleotides,
      which encodes a protein of 673 amino acids belonging to the G protein-coupled
      receptor superfamily with a large extracellular N-terminal domain involved in
      hormone recognition. The transmembrane domain ends with a short intracytoplasmic
      COOH-terminal domain involved in effector activation. Phylogenetic analysis
      showed that the lizard receptor belongs to the family of follicle-stimulating
      hormone (FSH) receptors. The hydrophobicity profile is similar to that observed
      for mammalian and avian FSH receptors. Northern blot analysis of total RNA
      revealed that the FSH receptor is expressed at high levels in the ovary. In situ
      hybridization experiments demonstrate that FSH receptor mRNA is specifically
      localized within the small cells of the follicular epithelium surrounding the
      oocyte.

PMID- 11574164
TI  - Cloning and expression of the human single copy homologue of the mouse zinc
      finger protein zfr.
AB  - A human homologue of the murine zinc finger protein zfr is transcriptionally
      induced in the Epstein-Barr virus-positive Burkitt lymphoma cell line Raji upon
      treatment with the granulocyte/macrophage lineage ganglioside IV(3)NeuAc
      nLcOse(4)Cer. The gene was cloned by a rapid amplification of cDNA ends approach
      based on a cDNA clone. The resulting hzfr sequence is 3393 base pairs in length
      coding for a protein of 1057 amino acids. Sequence alignments between hzfr and
      zfr reveal an identity of 92% on the nucleotide level and an identity of 96.4% on
      the amino acid level, respectively. Based on Southern blot data hzfr can be
      addressed as a single copy gene. Tissue-specific expression was determined by
      semi-quantitative PCR of normalized cDNA populations from various human tissues
      with glyceraldehyde-3-phosphate dehydrogenase as an internal control. Highest
      levels of transcripts were found in brain. hzfr transcripts could not be detected
      in skeletal muscle.

PMID- 11574165
TI  - Transcriptional repression of p21(waf1) promoter by hepatitis B virus X protein
      via a p53-independent pathway.
AB  - The X-gene product of hepatitis B virus (HBx) has been implicated in hepatitis B
      virus (HBV)-mediated hepatocellular carcinoma through its ability to induce liver
      cancer in some transgenic mice and to transactivate a variety of viral and
      cellular promoters. In this study, we demonstrated that the level of p21(waf1)
      RNA was decreased in the HBx-expressing cells and this effect was due to the
      transcriptional repression of the p21(waf1) gene by HBx via a p53-independent
      pathway. As the Sp1 binding sites of the p21(waf1) promoter were sufficient to
      confer HBx responsiveness to a previously non-responsive promoter, we suggested
      that HBx represses the transcription of p21(waf1) by downregulating the activity
      of Sp1. Because the tumor repressor p21(waf1) protein is a universal inhibitor of
      cyclin-CDK complexes and DNA replication that induces cell cycle arrest at the G1
      S checkpoint, the repression of p21(waf1) by HBx might play an important role in
      a HBV-mediated pathogenesis.

PMID- 11574166
TI  - Promoter structure and gene expression of the mouse inositol 1,4,5-trisphosphate
      receptor type 3 gene.
AB  - Inositol 1,4,5-trisphosphate receptor type 3 (IP(3)R3) is a ubiquitously
      expressed IP(3)R gene in the IP(3)R gene family. We identified an upstream region
      of the mouse IP(3)R3 genomic DNA. Transcription start points for the IP(3)R3 gene
      were found to be located mainly at four sites between nucleotide position -325
      and -285 relative to the first ATG codon. The major start point was mapped around
      -325. Transcription promotion ability was detected between -325 and -285 in an
      IP(3)R3 proximal promoter sequence. The promoter had no TATA-box but was highly
      GC-rich and contained two putative Sp1-binding sites. There was no sequence
      similarity between promoter regions of IP(3)R3 and IP(3)R2, another ubiquitous
      gene, except for GC-boxes. By using a series of 5'-truncation versions and a
      transient luciferase assay, we detected multiple common and cell-type-dependent
      regulatory regions within the distal promoter sequence downstream from -4.0 kb
      that function positively or negatively. The IP(3)R3 gene was highly transcribed
      in the kidney, spleen, heart, and skeletal muscle, and this tissue distribution
      pattern was nearly complementary to that of IP(3)R2. We found that IP(3)R3 gene
      expression was repressed in retinoic acid-treated and neural differentiated P19
      mouse embryonic carcinoma cells.

PMID- 11574167
TI  - Molecular cloning and characterization of a thioredoxin/nucleoside diphosphate
      kinase related dynein intermediate chain from the ascidian, Ciona intestinalis.
AB  - Flagellar outer arm dynein from the ascidian, Ciona intestinalis, contains five
      intermediate chains (IC1-5). Molecular cloning of C. intestinalis IC3 shows
      significant sequence homology to the dynein intermediate chain (IC1) from sea
      urchin and human NM23-H8 protein. The N-terminal thioredoxin-related region is
      well conserved in the C. intestinalis IC3, sea urchin IC1, and human NM23-H8
      protein. Three NDP kinase (NDPK)-related sequences are present in middle portions
      of both C. intestinalis IC3 and sea urchin IC1, but the human NM23-H8 protein had
      only two. A large part of the C-terminal glutamic acid-rich region present in sea
      urchin IC1 was greatly reduced in C. intestinalis IC3 and completely lost in
      human NM23-H8. Thus, thioredoxin/NDPK-related dynein intermediate chains (TNDK
      DIC) would be a characteristic of metazoan flagella and they have become smaller
      in size and less acidic during evolution.

PMID- 11574168
TI  - Promoter characterization of the human and mouse epilysin (MMP-28) genes.
AB  - Epilysin (MMP-28) is a recently cloned member of the matrix metalloproteinase
      family (Lohi et al., J. Biol. Chem. 276 (2001) 10134). It is expressed at highest
      levels in the skin by basal and suprabasal keratinocytes, and in testis by
      developing germ cells. To characterize the epilysin promoter, we isolated a 3.0
      kb fragment of human genomic DNA containing 5'-flanking sequence of the epilysin
      gene, and a corresponding 660 bp fragment from the mouse. The 5'-flanking
      sequences contain no typical TATA-boxes or CCAAT sequences close to the
      translation initiation sites. RNase protection assay revealed that two
      transcription start sites are utilized in the human epilysin gene, situated 210
      and 230 bp upstream from the translation start site. The promoter contains a GT
      box, situated 300 bp upstream from the translation start site, with homology to
      the consensus binding site for transcription factors of the Sp family. This site
      is perfectly conserved between the human and mouse promoters. For reporter gene
      assays a series of constructs with fragments of increasing length of the epilysin
      promoter were coupled to the firefly luciferase gene. Reporter gene assays
      indicated that deletion or mutation of the GT-box dramatically reduces the
      transcriptional activity both in keratinocytes and in spermatogonia. Gel mobility
      shift assays showed that several nuclear proteins bind specifically to this
      sequence. Supershift assays with antibodies specific for members of the Sp family
      identified Sp1 and Sp3 as components of these protein/DNA complexes and hence as
      possible regulators of the epilysin gene. Our results indicate that the epilysin
      promoter has distinctive structural and functional features, which may control
      the unique expression and regulation patterns of the epilysin gene.

PMID- 11574169
TI  - Partial protection and intrathecal invasion of CD8(+) T cells in acute canine
      distemper virus infection.
AB  - Initial non-inflammatory demyelination in canine distemper virus infection (CDV)
      develops against a background of severe immunosuppression and is therefore,
      thought to be virus-induced. However, recently we found a marked invasion of T
      cells throughout the central nervous system (CNS) in dogs with acute distemper
      despite drastic damage to the immune system. In the present study, this apparent
      paradox was further investigated by immunophenotyping of lymphocytes, following
      experimental CDV challenge in vaccinated and non-vaccinated dogs. In contrast to
      CDV infected, unprotected dogs, vaccinated dogs did not become immunosuppressed
      and exhibited a strong antiviral immune response following challenge with
      virulent CDV. In unprotected dogs rapid and drastic lymphopenia was initially due
      to depletion of T cells. In peripheral blood, CD4(+) T cells were more sensitive
      and depleted earlier and for a longer time than CD8(+) cells which recovered
      soon. In the cerebrospinal fluid (CSF) we could observe an increase in the T cell
      to B cell and CD8(+) to CD4(+) ratios. Thus, partial protection of the CD8(+)
      cell population could explain why part of the immune function in acute distemper
      is preserved. As found earlier, T cells invaded the CNS parenchyma in these dogs
      but also in the protected challenged dogs, which did not develop any CNS disease
      at all. Since markers of T cell activation were upregulated in both groups of
      animals, this phenomenon could in part be related to non-specific penetration of
      activated T cells through the blood brain barrier. However, in diseased animals
      much larger numbers of T cells were found in the CNS than in the protected dogs,
      suggesting that massive invasion of T cells in the brain requires CDV expression
      in the CNS.

PMID- 11574170
TI  - Molecular epidemiology of classical swine fever in Italy.
AB  - To gain an insight into the molecular epidemiology of classical swine fever (CSF)
      in Italy, virus isolates originating from outbreaks that occurred between 1985
      and 2000 in wild boar or in domestic pigs in mainland Italy and in Sardinia were
      analysed by genetic typing. For this, a fragment (190 nucleotides) of the E2
      glycoprotein gene was sequenced and phylogenetic analyses were performed,
      including older Italian isolates and isolates from recent outbreaks in Europe for
      comparison. The results show that in mainland Italy, several independent
      epidemiological events occurred in the last decade. In the north of the country,
      viruses of genotype 2.2 have persisted in wild boar, causing sporadic outbreaks
      in domestic pigs. In contrast, viruses of subgroups 2.1 and 2.3 appeared only
      intermittently in different regions of the mainland. In 1997, classical swine
      fever virus (CSFV) isolates belonging to the subgroup 2.1 and genetically and
      epidemiologically related to the Dutch isolate in Venhorst, affected domestic
      pigs exclusively. The isolates of subgroup 2.3, derived from wild boar as well as
      from domestic pigs were closely related to isolates from Germany and Poland. In
      Sardinia, CSF is an endemic in wild boar and affects domestic pigs also. Genetic
      typing showed that viruses of subgroups 1.1 and 2.3 have been present, the last
      ones being unrelated to the mainland viruses of the same subgroup. Due to the
      large quantities of pig and wild boar meat imported in some parts of Italy, it
      cannot be established if these viruses were always present in either the mainland
      or Sardinia, or if they represent recent introductions.

PMID- 11574171
TI  - Experimental infection of European red foxes (Vulpes vulpes) with canine
      herpesvirus.
AB  - We report on the pathogenicity of canine herpesvirus (CHV) for European red
      foxes. In the first experiment, we inoculated 10 adult foxes intravenously with a
      canine isolate of CHV. All foxes became infected and shed CHV in saliva and
      genital secretions for up to 14 days post-inoculation (p.i.) as evaluated by PCR
      and/or by virus isolation. All foxes developed clinical signs such as fever,
      lethargy and evidence of respiratory tract disease. Two foxes died on day 6 p.i.,
      one on day 7 p.i., and one fox was euthanased on day 6 p.i. Tissues taken from
      the four dead foxes were positive for CHV by PCR. The remaining six foxes
      recovered after approximately 14 days p.i. Virus particles with morphology
      typical of herpesviruses were found by electron microscopy in the liver of an
      infected animal. All surviving foxes developed serum anti-CHV antibodies. In a
      second experiment, six foxes were dosed perorally with CHV and paired with six
      untreated controls. Neither the perorally dosed nor the in-contact control foxes
      developed clinical signs of disease. Infectious CHV was not isolated from any of
      the dosed or the in-contact foxes but all perorally-infected foxes and one of the
      in-contact foxes tested PCR-positive for CHV on several occasions p.i. All
      perorally-infected foxes, but none of the in-contact foxes, seroconverted. In
      summary, intravenous CHV inoculation caused a clinical disease in adult foxes
      much more severe than observed in experimentally-infected adult dogs. No clinical
      disease or virus spread was observed after peroral dosing although viral
      infection occurred as evidenced by seroconversion.

PMID- 11574172
TI  - Seroprevalence of bovine leukemia virus in dairy cattle in Argentina: comparison
      of sensitivity and specificity of different detection methods.
AB  - Bovine leukemia virus (BLV) is a retrovirus that induces a chronic infection in
      cattle, which develop in three possible pathological forms: asymptomatic course,
      persistent lymphocytosis (PL) and lymphosarcoma. Once infected, cattle remain
      virus carriers for life and start to show a serological reaction within a few
      weeks after infection. Eradication and control of the disease is based on early
      diagnostic and segregation of the carriers. The agar gel immunodiffusion (AGID)
      test has been the serological test of choice for routine diagnosis of serum
      samples. Nevertheless, in more recent years, the enzyme-linked immunosorbent
      assay (ELISA) has replaced the AGID for large scale testing. Although Argentina
      has over 60 million cattle population, no nationwide studies have been conducted
      yet to determine the prevalence of the infection. To estimate the rate of BLV
      infection in dairy cattle in Argentina, a survey for specific antibodies in
      >10,000 serum samples from animals over 18 months old, belonging to 363 different
      herds from the largest dairy production areas of the country, was carried out in
      our laboratory, along 1999. For this purpose, we developed an ELISA to detect
      serum antibodies against the BLV virus. The cut-off of the ELISA was established
      over 339 serum samples, using polymerase chain reaction and southern blot (PCR
      SB) as confirmatory test. The sensitivity and specificity of the ELISA was of
      97.2 and 97.5%, respectively, while the local official AGID test showed a
      sensitivity of 79.7% and specificity of 99.0%. To know the seroprevalence of BLV
      on dairy herds, and also the incidence of the infection within the herd, the
      serological survey was based on individual serum samples. The results show that
      the prevalence of infected individuals is of 32.85%, while the percentage of
      infected herds, harboring one or more infected animals, is of 84%. These results
      indicate a medium level of seropositive animals when taken individually, but a
      high prevalence of infected farms, which has been notoriously increased in the
      last 15 years as shown when compared with previous data from particular
      geographic areas, indicating that BLV constitutes a serious sanitary problem for
      dairy producers in Argentina. They also indicate the poor sensitivity of the
      official AGID test used in the country.

PMID- 11574173
TI  - Genetic variation and phylogenetic analyses of the ORF5 gene of acute porcine
      reproductive and respiratory syndrome virus isolates.
AB  - Swine herds in the US have experienced recent outbreaks of a severe form of
      porcine reproductive and respiratory syndrome (designated acute or atypical PRRS)
      characterized by abortion and high mortality in pregnant sows. Most of the
      affected herds had been vaccinated with modified live-vaccines (MLVs) against
      PRRS. To explore the possible mechanism of the emergence of acute PRRS, the open
      reading frame 5 (ORF5) gene encoding the major envelope protein (GP5) of acute
      PRRSV isolates was characterized. The complete ORF5 gene of eight acute PRRSV
      isolates from herds experiencing acute PRRS outbreaks in Iowa and North Carolina
      was amplified and sequenced. Sequence analyses revealed that these acute PRRSV
      isolates shared 88-95% nucleotide and 88-96% amino acid sequence identities to
      each other, 87-97% nucleotide and 84-96% amino acid sequence identities with
      other North American PRRSV isolates and the MLVs. Most of the amino acid
      substitutions locate in the putative signal sequence and two short hypervariable
      regions at the amino terminus. The ORF5 gene sequence of the acute PRRSV isolate
      98-37120-2 from a non-vaccinated swine herd in Iowa is very closely related to
      that of the RespPRRS MLV, with 97% nucleotide and 96% amino acid sequence
      identities. Phylogenetic analysis revealed that all eight acute PRRSV isolates
      are clustered within the North American genotype. Several minor branches that are
      not associated with geographic origins were also identified within the North
      American genotype. One acute PRRSV isolate (98-37120-2) is clustered with the
      RespPRRS MLV and several Danish isolates that were confirmed to be derived from
      the RespPRRS MLV. The ORF5 gene sequences of other seven acute isolates are more
      related to those of several earlier PRRSV isolates and the PrimePac MLV than to
      that of the RespPRRS MLV. Our results showed that the acute PRRSV isolates
      analyzed in this study differed from each other in ORF5 genes, although they all
      clustered within the North American genotype. The data from this study do not
      fully support the hypothesis that the emergence of acute PRRS is due to reversion
      of MLVs to a pathogenic phenotype, as only one of the eight acute isolates was
      shown to be very closely related to the RespPRRS MLV.

PMID- 11574174
TI  - Distribution pattern of bovine viral diarrhoea virus strains in intensive cattle
      herds in Italy.
AB  - The genetic variation of bovine viral diarrhoea virus (BVDV) was studied by
      comparative nucleotide sequence analysis of 26 Italian field strains collected
      during the period 1995-2000 in 18 cattle herds. A fragment within the 5'
      untranslated region (UTR) was sequenced directly from gel-purified products
      obtained by reverse transcription polymerase chain reaction. BVDV-1b (n=14), -1c
      (n=1), -1d (n=1) and BVDV-2 (n=2) strains have been isolated. Most herds were
      infected by BVDV-1b. Pairwise similarity and cluster analysis of the remaining
      BVDV-1 isolates (n=8) did not provide a clear-cut assignation to defined BVDV-1
      groups. This is the first time that a BVDV-2 isolation was reported in Italy.
      Among BVDV-2 reference strains, Italian BVDV-2 isolates showed the highest
      sequence similarity with the CD87 strain. Both BVDV-2 strains were isolated in
      two healthy animals from different herds. The 5'-UTR sequence of one of the two
      BVDV-2 strains was identical to a German BVDV field strain. Complete nucleotide
      homology was found only among BVDV strains isolated from the same herd, showing a
      herd-specific clustering. Moreover, 99.6% homology was observed between strains
      from herds linked by livestock trade. Despite the small number of BVDV isolates
      analysed, it revealed a high level of genetic diversity among Italian field BVDV
      strains.

PMID- 11574175
TI  - Organisation and in vitro expression of esp genes of the LEE (locus of enterocyte
      effacement) of bovine enteropathogenic and enterohemorrhagic Escherichia coli.
AB  - Enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli infections
      are characterised by the formation of attaching and effacing (AE) lesions on
      intestinal epithelial cells. Secretion of extracellular proteins (EspA, EspB, and
      EspD) via a type III secretion apparatus is necessary for the formation of the AE
      lesions by human EPEC. In this study, we show that bovine EPEC and EHEC are also
      able to secrete polypeptides homologous to the already described Esp proteins,
      most probably via a type III secretion system. Bovine EPEC and EHEC strains
      present two different secretion profiles of Esp proteins which correlate to the
      pathotypes of the esp genes as determined by PCR. We also demonstrate that genes
      encoding secreted proteins, present in the LEE of two bovine strains, are
      organised in the same way as in the human EPEC strain E2348/69.

PMID- 11574176
TI  - Prevalence and mechanism of resistance against macrolides and lincosamides in
      Streptococcus suis isolates.
AB  - Eighty-seven Streptococcus suis isolates recovered in 1999-2000 from diseased
      pigs, all from different farms, were screened for resistance against macrolide
      and lincosamide antibiotics by the disk diffusion and agar dilution test and a
      PCR assay, amplifying the ermB gene and the mefA/E gene. Seventy-one percent of
      the isolates showed constitutive resistance to macrolide and lincosamide
      antibiotics (MLS(B)-phenotype). All these isolates were positive for the ermB
      gene in the PCR, but negative for the mefA/E gene. For all strains minimum
      inhibitory concentrations (MIC) against five other antimicrobial agents were
      determined. All strains were susceptible to penicillin. Ninety-nine percent of
      the isolates were susceptible to enrofloxacin and tiamulin. Eighty-five percent
      of the strains were resistant to doxycycline. A 540bp fragment of the ermB genes
      of eight S. suis strains was sequenced and compared with ermB genes of five S.
      pneumoniae and five S. pyogenes strains of human origin. A 100% homology was
      found between these fragments in seven S. suis, one S. pneumoniae and three of
      the S. pyogenes isolates. This study demonstrates that resistance against
      macrolides, lincosamides and streptogramin B is widespread in S. suis and
      mediated by ribosome methylation, encoded by the ermB gene.

PMID- 11574177
TI  - A survey of physicians' attitude towards women with postmenopausal bleeding.
AB  - OBJECTIVE: To study how gynaecologist manage postmenopausal bleeding in women not
      using HRT. The impact on the physicians' attitude of risk factors for endometrial
      cancer and of the endometrial thickness was essentially accounted for. METHODS:
      Two different case-types were defined by modifying the risk level of developing
      endometrial cancer. Also the level of endometrial thickness, assessed by
      ultrasound, was made to vary. In total four case-types were constructed. One case
      type was sent at random to each Belgian gynaecologist (n=970). RESULTS: Response
      rate: 55%. The proportion of physicians who would not investigate the patients'
      endometrium varied between 2% (high-risk patient with abnormal ultrasound) and
      34% (low risk patient, normal ultrasound). Significant differences were observed
      in relation to the level of risk factors for endometrial cancer and in relation
      to endometrial thickness. No significant relationship was found between the
      choice of the method of endometrial investigation and the risk situation or the
      ultrasound result. CONCLUSIONS: The attitude of Belgian gynaecologists towards
      postmenopausal bleeding is modified by the presence of risk factors and by the
      level of endometrium thickness. About one third of physicians would not further
      investigate the endometrium of a patient with a low risk profile and a normal
      endometrium as assessed by ultrasound.

PMID- 11574178
TI  - Five-year compliance with hormone replacement therapy in postmenopausal Chinese
      women in Hong Kong.
AB  - OBJECTIVES: To assess 5-year compliance with hormone replacement therapy (HRT) in
      Hong Kong Chinese women and the reasons for long-term compliance or non
      compliance. METHODS: A telephone survey using a standardized questionnaire was
      conducted in 187 postmenopausal women who had commenced HRT in a referral-only
      specialist clinic of a university teaching hospital 5 years previously. Over this
      5-year period, the cohort had been referred out to primary care doctors once they
      had become stabilized on treatment. RESULTS: The 5-year compliance rate was
      71.1%. The overall compliance rates were nearly the same from 2 and 5 years.
      'Doctors' advice' was the most important reason for maintenance of long-term
      compliance, accounting for 88.0% of all compliant cases. The most frequent reason
      for non-compliance was that of the experience of side effects. Other important
      reasons were fear of cancer, fear of other side effects, and discouragement from
      other doctors. Overall, 16.0% of women expressed concern regarding potential side
      effects or risk of breast cancer. Younger age at menopause and at time of initial
      consultation, shorter duration of menopause at presentation and previous history
      of hysterectomy were associated with a higher degree of compliance at 5 years.
      Presence or absence of menopausal symptoms, on the other hand, was not a
      significant factor. CONCLUSIONS: The 5-year compliance rate in this cohort of
      Hong Kong Chinese women was comparable to that reported from predominantly
      Caucasian populations. The physicians' role in encouraging postmenopausal women
      to achieve long-term HRT compliance was observed.

PMID- 11574179
TI  - Triglyceride and lipoprotein (a) are markers of coronary artery disease severity
      among postmenopausal women.
AB  - OBJECTIVE: After menopause, some women manifest coronary artery disease (CAD)
      with highly variable angiographic severity. For these women, postmenopausal
      appearing of some CAD risk factors may have differently influenced the CAD risk
      and severity. In this study, we attempt to unravel differences in the frequency
      or intensity of CAD risk factors among postmenopausal women with different
      angiographic severity. METHODS: We studied 182 postmenopausal women (64+/-6
      years) who underwent coronary angiography to investigate thoracic pain. Subjects
      with no detectable coronary lesions at angiography were recruited to the non
      obstructive group and patients with CAD were grouped in one-vessel or multi
      vessel groups. We compared clinical variables as the body mass index (BMI), age
      at menopause, age, hypertension, diabetes and cigarette smoking, and lipid
      measurements as plasma levels of total cholesterol, triglyceride, low-density
      lipoprotein cholesterol, very low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, apolipoprotein (apo) A1, apo B and lipoprotein(a)
      (Lp(a)). RESULTS: Comparing to the non-obstructive group, Lp(a) was twofold
      higher in the one-vessel group and threefold higher in the multi-vessel group and
      triglycerides were 34% higher in the one-vessel group and 50% higher in the multi
      vessel group. No further difference was found among the three groups. After
      multivariate logistic regression analysis, triglyceride (odds ratio: 1.01;
      P=0.0013) and Lp(a) (odds ratio: 1.006; P<0.0001) were independently indicative
      of the presence of obstructive CAD. CONCLUSIONS: We found that both Lp(a) and
      triglycerides constitute useful markers of CAD severity among postmenopausal
      women.

PMID- 11574180
TI  - Effect of hormone replacement therapy on lipids in perimenopausal and early
      postmenopausal women.
AB  - OBJECTIVE: To determine the effects of oral sequential hormone replacement
      therapy (HRT) on lipid-profile in perimenopausal and early postmenopausal women.
      METHODS: We performed a single-center, randomized, placebo-controlled trial. The
      trial was double blind with respect to 17beta-estradiol/desogestrel (17beta-E-D)
      and placebo and open with respect to conjugated estrogens/norgestrel (CEE-N). A
      total of 125 healthy perimenopausal and early postmenopausal women, aged 43-58
      years, were recruited from the general population in Zoetermeer, the Netherlands.
      The intervention consisted of 6 months treatment with 1.5 mg 17beta
      estradiol/0.15 mg desogestrel (n=53), 0.625 mg conjugated estrogens/0.15 mg
      norgestrel (n=36) or placebo (n=36). At baseline, cycle 1, 3 and 6, overnight
      fasting blood samples were obtained in which lipids were determined. We used
      linear regression analysis to calculate differences in mean change from baseline
      in lipids in the active treatment groups compared to placebo. RESULTS: In both
      treatment groups significant (P<0.05) falls in low-density-lipoprotein (LDL)
      cholesterol (17beta-E-D: -7.8% and CEE-N: -8.4%) and lipoprotein(a) (17beta-E-D: 
      11.7% and CEE-N: -28.3%) were found compared to placebo. Apolipoprotein A1
      (17beta-E-D: 6.8% and CEE-N: 7.3%) and HDL-cholesterol (17beta-E-D: 6.4% and CEE
      N: 8.0%) significantly increased compared to placebo. No significant changes were
      found in the other lipids. Mean changes from baseline in total cholesterol, LDL
      cholesterol and apolipoprotein B were significantly more pronounced in
      postmenopausal women compared to perimenopausal women, adjustment for age
      differences did not change the results. CONCLUSION: Treatment of perimenopausal
      and early postmenopausal women with 17beta-E-D or CEE-N changes their lipid
      profile in a potentially anti-atherogenic direction. Changes appear to be more
      pronounced in postmenopausal women compared to perimenopausal women.

PMID- 11574181
TI  - A prospective study on women with a history of breast cancer and with or without
      estrogen replacement therapy.
AB  - OBJECTIVE: Because a categorical refusal of estrogen replacement therapy (ERT)
      from postmenopausal patients with a history of breast cancer is not based on any
      research evidence and may be more harmful than beneficial, we evaluated the
      safety and efficacy of ERT in these women. METHODS: We recruited 131 patients who
      had been treated for breast cancer for a mean of 4.2 years (range 1 month to 20
      years) before. Eighty-eight decided to use ERT, whereas 43 refused or had no need
      for ERT. At recruitment, the patients were carefully examined for breast and
      gynaecologic findings. Non-hysterectomized patients wishing to receive ERT (n=54)
      then started using estradiol as oral tablets (2 mg/day) (n=44) or as transdermal
      gel (1.5 mg/day) (n=10) in combination with 10-day courses of oral
      medroxyprogesterone acetate at 4-week intervals, whereas hysterectomized patients
      (n=34) used only estradiol, orally (2 mg/day) (n=31) or transdermally (1.5
      mg/day) (n=3). The patients using ERT were carefully examined 6 and 12 months
      later, and then annually at a specific outpatient department, and the mean follow
      up time is now 2.5 years (range from 1 month to 5.2 years, 216 woman-years). The
      43 patients not wishing to receive ERT were followed annually at the oncologic
      department for a mean of 2.6 years (range from 1 month to 4.7 years), and served
      as a control group. RESULTS: ERT significantly reduced climacteric symptoms, and
      the Kupperman score fell by 63%, from 26.9+/-8.6 to 9.9+/-6.7 (mean+/-SD). In non
      hysterectomized women, medroxyprogesterone acetate triggered withdrawal bleeding
      in all except seven women. Seven patients (13%) experienced spotting during ERT.
      In 27 women, endometrial thickness exceeded 10 mm, and two of the total of 54
      patients (3.7%) had simple hyperplasia. This vanished spontaneously in 3-6
      months. Ten patients terminated the use of ERT within the first 12 to 39 months
      due to the lack of severe vasomotor symptoms (n=4) or due to the recurrence of
      breast cancer or to cancer of the contralateral breast (n=6). Eighty-one of the
      88 patients (92%) using ERT showed no evidence of recurrence, whereas five
      patients (5.7%) had recurrence in 12-36 months and two patients (2.3%) developed
      a cancer of the contralateral breast in 14-24 months; another one of those wanted
      to continue with ERT. Thus the combined risk of recurrence or a new cancer of the
      contralateral breast in ERT users was 7/216 woman-years (3% per year). In the
      control group, 38 of 43 patients (88.4%) showed no evidence of recurrence or
      contralateral cancer, whereas four patients had recurrence and one developed a
      contralateral breast cancer (5/112 woman-years, 4% per year). CONCLUSIONS:
      Symptomatic climacteric patients with a history of breast cancer benefited from
      ERT without increasing their risk of recurrence, but the short follow-up and the
      small number of patients limit any definitive recommendations.

PMID- 11574182
TI  - Cell cycle analysis and detection of proliferative cell nuclear antigen of the
      endometrium after hormone replacement therapy.
AB  - BACKGROUND: To understand the effect of sequential combined hormone replacement
      therapy (HRT) on the postmenopausal endometrium. METHODS: Sonographic endometrial
      thickness, endometrial histopathology, flow cytometric cell cycle analysis and
      the level of proliferative cell nuclear antigen (PCNA) were studied. RESULTS: One
      hundred and thirty-eight postmenopausal women were enrolled in this study. Among
      which, 97 women had their endometrium being adequately obtained; the most
      frequent type of histopathology was normal endometrium (91.8%). Endometrial
      hyperplasia was found in seven patients (7.2%), including typical simple
      hyperplasia (n=1, 1%), focal simple hyperplasia (n=5, 5.2%) and complex
      hyperplasia without atypia (n=1, 1%). The proliferative fractions (PF; S plus G2
      M phase) of cells from normal and hyperplastic endometrium of menopausal women
      after HRT were 8.18 and 8.95%, respectively, which were lower than those from 29
      premenopausal women without HRT. The level of PCNA of normal and hyperplastic
      endometrium in postmenopausal women after HRT was about 80 and 84%, respectively,
      of that from premenopausal endometrium. CONCLUSIONS: Our study showed the PF of
      the cell cycle and the level of PCNA were not increased in the menopausal
      endometrium under HRT as compared to the premenopausal controls.

PMID- 11574183
TI  - Ultrasonographic endometrial monitoring during continuous-sequential hormonal
      replacement therapy regimen in postmenopausal women.
AB  - OBJECTIVE: To evaluate the endometrial thickness in different periods of a
      continuous-sequential HRT regimen and to correlate the ultrasonographic findings
      with the histological patterns. METHODS: The study was structured in two phases.
      In the 1st phase, 37 postmenopausal women (group A) treated by at least 6 months
      with a conventional continuous-sequential hormonal replacement therapy (cs-HRT)
      regimen were enrolled. In all patients, the endometrial thickness was measured at
      the 7th, 14th, 21st and 25th day of the cycle using transvaginal ultrasonography
      (TV-USG). In the 2nd phase of the study, other 41 postmenopausal women (group B)
      were enrolled and treated with the same sc-HRT regimen. At entry and after six
      cycles of cs-HRT, an endometrial biopsy was performed. The endometrial pattern
      was related with endometrial thickness. Either the evaluations were performed
      immediately after progestogen withdrawal bleeding, as showed by 1st phase
      results. RESULTS: The results of the 1st phase of the study showed a mean
      endometrial thickness significantly lower at 7th day of the cycle compared to
      14th, 21st and 25th day (4.3+/-1.2 versus 6.6+/-2.9, 7.8+/-4.2 and 7.4+/-4.6 mm+/
      SD, respectively). After six cycles of cs-HRT (2nd phase of the study), the mean
      endometrial thickness was significantly increased in comparison with basal values
      (4.2+/-1.5 versus 2.8+/-1.2 mm+/-SD; P<0.05). Endometrial biopsies showed 13
      cases (39.4%) of atrophy and 20 cases (60.6%) of proliferative endometrium. Mean
      endometrial thickness in case of atrophy was lower than in presence of a
      proliferative endometrium (3.7+/-1.2 versus 4.4+/-1.4 mm+/-SD; not significant).
      Endometrial thickness was <4 mm in 16 cases (11 of atrophic and five of
      proliferative endometrium), between 4 and 5 mm in 15 cases (13 of proliferative
      and two of atrophic endometrium) and between 5 and 6 mm in two cases (either case
      of proliferative endometrium). CONCLUSIONS: The best timing for monitoring
      endometrial thickness during cs-HRT regimens is the period immediately after
      withdrawal bleeding improving the reliability of the ultrasonographic exam to
      identify endometrial pathologies.

PMID- 11574184
TI  - Anti-ischemic effect of chronic oestrogen replacement therapy alone or in
      combination with medroxyprogesterone acetate in different replacement schemes.
AB  - BACKGROUND: Oestrogen replacement therapy in postmenopausal women has a
      protective effect upon the cardiovascular system and improves exercise-induced
      myocardial ischemia. Although in hormone replacement schemes progestins are
      required to reduce the likelihood of uterine malignancies, little is known on the
      cardiovascular effect of progestins. The purpose of this study was to evaluate
      the effect of oestrogen replacement alone and two different estrogen-progestin
      replacement therapy schemes upon exercise induced myocardial ischemia. MATERIAL
      AND METHOD: The study population included 18 female menopausal patients with
      coronary artery disease. After a baseline exercise test patients received
      conjugated equine estrogens (CEE) 0.625 mg alone for 30 days when they underwent
      a second exercise test and were randomized to receive in a cross-over design
      medroxyprogesterone acetate (MPA) either in continuous combined therapy (2.5
      mg/daily) for 28 days or in cyclical therapy (10 mg o.d. from day 16 to day 28).
      RESULTS: After CEE alone two patients with a previously positive exercise test
      showed a negative exercise test. CEE increased time to 1 mm ST compared to
      baseline (352+/-185 vs 265+/-133 s, P<0.01). In the 2 pts in whom the exercise
      test was negative after CEE the test remained negative during continuous combined
      MPA therapy while become positive during cyclical MPA. CEE+continuous combined
      MPA increased both time to 1 mm ST and exercise time compared to baseline (386+/
      165 vs 265+/-133 s, P<0.01 and 545+/-198 vs 465+/-186 s, P<0.05, respectively).
      No difference was found between baseline and CEE+cyclical MPA in either time to 1
      mm ST or exercise time (268+/-164 vs 265+/-133 s, P=NS and 455+/-223 vs 465+/-186
      s, P=NS, respectively). CONCLUSION: Continuous combined therapy with CEE+MPA
      improves exercise-induced myocardial ischemia in female patients with coronary
      artery disease while the beneficial effect of CEE is reduced by cyclical therapy.

PMID- 11574185
TI  - Short term oral estriol treatment restores normal premenopausal vaginal flora to
      elderly women.
AB  - OBJECTIVE: Estriol is an estrogen with considerably weaker stimulatory effects on
      endometrial proliferation than estradiol. A study was conducted to determine the
      effects of oral estriol on vaginal flora and endometrial thickness. METHODS:
      Fifty-nine postmenopausal women (50-75 years of age), complaining of pruritus or
      vaginal discharge, participated in the study. Vaginal flora and endometrial
      thickness were evaluated before treatment and after receiving oral estriol (2
      mg/day) for 14 days. RESULTS: Prior to treatment, lactobacilli were found in
      vaginal cultures from only six of the 59 study participants, whereas after
      treatment, the vaginal flora of 27 women showed a presence of lactobacilli
      (P<0.0001). Endometrial thickness exceeded 5 mm in only five cases. No side
      effects were reported. CONCLUSION: Estriol, which has little effect on the
      endometrium, has the potential to be highly useful for the treatment of atrophic
      vaginitis.

PMID- 11574186
TI  - Bilateral ovarian fibromas and endometrial adenocarcinoma in a postmenopausal
      patient with growing uterine myomas.
AB  - Bilateral ovarian fibromas are a rare condition. We report a case of bilateral
      ovarian fibromas with endometrial adenocarcinoma in a postmenopausal woman who
      clinically showed symptoms of an estrogen-producing tumour. Clinical and
      histopathological problems in the pre- and intraoperative diagnostics of fibromas
      are discussed.

PMID- 11574187
TI  - A simplified method to quantitate atherosclerosis in the rabbit aorta.
AB  - A simple method to quantitatively evaluate atherosclerosis in the rabbit aorta by
      measuring macroscopic lesion areas (%) was attempted in the present study. Ten
      female New Zealand white rabbits were fed on a cholesterol-rich diet (5/1000 g of
      food) during 4 months. Five of them were oophorectomized at the beginning and all
      were sacrificed at the end. Total levels of cholesterol increased from 50.7+/
      14.7 mg/dl to 782.8+/-296.0. No significant differences were observed between
      oophorectomized and intact rabbits. At 4 months, the cholesterol-rich diet caused
      in both, intact and oophorectomized rabbits, atherosclerotic lesions affecting 17
      and 46% of the aortic surface, respectively. This method may be more practical,
      easy and useful for quantitative evaluation of aortic atherosclerosis in a large
      number of rabbits, than histological observations of serial sections of rabbit's
      aortas.

PMID- 11574188
TI  - Macrolides: structures and microbial targets.
AB  - The macrolide class of antibiotics is well established and often recommended for
      use in the treatment of community-acquired respiratory tract infections. A number
      of agents with varying antimicrobial activity have been developed via chemical
      modification of the core macrolide structure, a macrocyclic lactam ring. Although
      structurally diverse, the macrolides share a common ability to bind to the
      bacterial 50S ribosome subunit and inhibit protein synthesis, thereby preventing
      bacterial multiplication. Resistance in the clinic is due to modification of the
      50S subunit in the area of the peptidyl transferase center or to an efflux pump.
      The newer macrolides, and in particular azithromycin, with their broad-spectrum
      microbiological profile have extended the therapeutic uses of this class of
      antibiotics and ensured that they remain an integral part of the clinician's
      armamentarium.

PMID- 11574189
TI  - Advanced-generation macrolides: tissue-directed antibiotics.
AB  - The azalide antibiotic azithromycin and the newer macrolides, such as
      clarithromycin, dirithromycin and roxithromycin, can be regarded as 'advanced
      generation' macrolides compared with erythromycin, the first macrolide used
      clinically as an antibiotic. Their pharmacokinetics are characterized by a
      combination of low serum concentrations, high tissue concentrations and, in the
      case of azithromycin, an extended tissue elimination half-life. Azithromycin is
      particularly noted for high and prolonged concentrations at the site of
      infection. This allows once-daily dosing for 3 days in the treatment of
      respiratory tract infections, in contrast to longer dosage periods required for
      erythromycin, clarithromycin, roxithromycin and agents belonging to other classes
      of antibiotics. The spectrum of activity of the advanced-generation macrolides
      comprises Gram-positive, atypical and upper respiratory anaerobic pathogens.
      Azithromycin and the active metabolite of clarithromycin also demonstrate
      activity against community-acquired Gram-negative organisms, such as Haemophilus
      influenzae. Advanced-generation macrolides, and in particular azithromycin, are
      highly concentrated within polymorphonuclear leucocytes, which gravitate by
      chemotactic mechanisms to sites of infection. Following phagocytosis of the
      pathogens at the infection site, they are exposed to very high, and sometimes
      cidal, intracellular concentrations of antibacterial agent. Pharmacodynamic
      models and susceptibility breakpoints derived from studies with other classes of
      drugs, such as the beta-lactams and aminoglycosides, do not adequately explain
      the clinical utility of antibacterial agents that achieve high intracellular
      concentrations. In the case of azithromycin, attention should focus on tissue
      pharmacokinetic and pharmacodynamic concepts.

PMID- 11574190
TI  - Macrolides: pharmacokinetics and pharmacodynamics.
AB  - Three pharmacokinetic/pharmacodynamic parameters--(i) the peak concentration to
      the minimum inhibitory concentration ratio (C(max)/MIC); (ii) the area under the
      concentration-time curve to MIC ratio (AUC(24h)/MIC); and (iii) the time the
      concentration exceeds the MIC (T>MIC)--are important predictors of the clinical
      efficacy of antibiotics. For antibiotics with pronounced concentration-dependent
      killing, such as the fluoroquinolones or the aminoglycosides, C(max)/MIC and
      AUC(24)/MIC are the main factors that establish efficacy. Antibiotics with a
      weak, or no, concentration dependency generally have their efficacy linked to
      T>MIC, and these include the beta-lactams and the conventional macrolides.
      Antibiotics with weak concentration-dependent effects, but with prolonged
      persistent effects, such as tetracyclines and azithromycin, have their activity
      mostly related to the AUC(24)/MIC. By applying these concepts to current
      antibiotics, and also to the development of novel agents, it is possible to
      optimise their dosages and administration schedules. This will maximise
      therapeutic efficacy, may prevent or delay the emergence of bacterial resistance
      to antibiotics, and can certainly minimise side-effects.

PMID- 11574191
TI  - Macrolide resistance mechanisms in Gram-positive cocci.
AB  - Two principal mechanisms of resistance to macrolides have been identified in Gram
      positive bacteria. Erythromycin-resistant methylase is encoded by erm genes.
      Resultant structural changes to rRNA prevent macrolide binding and allow
      synthesis of bacterial proteins to continue. Presence of the erm gene results in
      high-level resistance. Modification of the mechanism whereby antibiotics are
      eliminated from the bacteria also brings about resistance. Bacteria carrying the
      gene encoding macrolide efflux (i.e. the mefE gene) display relatively low-level
      resistance. Azithromycin, because of its ability to achieve concentrations at
      sites of infections, is capable of eradicating mefE-carrying strains. Other
      resistance mechanisms, involving stimulation of enzymatic degradation, appear not
      to be clinically significant.

PMID- 11574192
TI  - Clinical relevance of laboratory susceptibility data.
AB  - The breakpoints for macrolides proposed by various organisation differ. In vitro
      studies may not give a true measure of breakpoints as culture conditions are not
      necessarily analogous to the in vivo situation. The effects of pH, carbon dioxide
      and culture media can affect the minimum inhibitory concentrations of macrolides;
      the extent of these effects varies for the different agents. Microbiological
      efficacy should ideally be proven under clinical conditions, but this is not
      always feasible. The breakpoints of macrolides should be reviewed taking into
      account the site of infection.

PMID- 11574193
TI  - The clinical impact of macrolide resistance in pneumococcal respiratory
      infections.
AB  - By the 1960s, several reports of bacteria with reduced susceptibility to
      antibiotics were published. In recent years, the problem of antibiotic resistance
      has magnified. In the treatment of respiratory tract infections, the development
      of resistance is of particular concern; 67% of antibiotic use in adults and 87%
      in children is for the treatment of such infections. Streptococcus pneumoniae is
      the most common cause of community-acquired pneumonia and is a frequently
      isolated bacterial species in patients with other respiratory tract infections.
      Increasing levels of resistance may have important implications in the clinical
      setting. Physicians need to consider local susceptibility data, in addition to
      the pharmacokinetic and pharmacodynamic features of compounds, when selecting
      appropriate antibiotics for the treatment of bacterial infections.

PMID- 11574194
TI  - Worldwide guidelines for respiratory tract infections: community-acquired
      pneumonia.
AB  - The management of respiratory tract infections is a complex process. Concern over
      increasing levels of bacterial resistance and the inappropriate use of
      antibiotics has led to the development of clinical guidelines for the treatment
      of respiratory tract infections. Despite the development of these guidelines, a
      consensus on the optimal care for lower respiratory tract infections has not been
      attained. Guidelines for the management of community-acquired pneumonia (CAP)
      have been developed since the 1990s in the USA, Canada, and a number of European
      countries. Constant re-evaluation of guidelines for CAP is necessary to ensure
      that the recommendations that were made in the early 1990s still hold true in the
      new millennium.

PMID- 11574195
TI  - Japanese guidelines for the management of community-acquired pneumonia.
AB  - Japanese guidelines for the management of community-acquired pneumonia (CAP) were
      published in March 2000. The guidelines differentiate between mild-to-moderate
      and severe pneumonia. A distinction is also made between bacterial and 'atypical'
      pneumonia.

PMID- 11574196
TI  - The place of antibiotic therapy in the management of chronic acute exacerbations
      of chronic bronchitis.
AB  - In the USA, more than 16 million adults are affected by chronic obstructive
      pulmonary disease, and chronic bronchitis has been estimated to affect up to 13
      million individuals or approximately 4-6% of adults. Chronic bronchitis is an
      increasing cause of significant morbidity and mortality. During acute
      exacerbations of chronic bronchitis, subjects experience a worsening of
      bronchitic symptoms, with an increase from baseline in one or more or the
      following; dyspnoea, cough and/or sputum volume, purulence or viscosity. The
      severity of an exacerbation can be graded by how many of these symptoms are
      present. Antibiotic therapy should be initiated based on patient history and
      severity of the exacerbation.

PMID- 11574197
TI  - Community-acquired pneumonia in ambulatory patients: relative importance of
      atypical pathogens.
AB  - The presence of atypical pathogens in community-acquired pneumonia is difficult
      to diagnose; culture is time-consuming and requires considerable expertise and
      serological identification may be inaccurate. Nevertheless, the increasing
      importance of atypical organisms has been recognised in recent years. Variations
      in aetiology have been detected in different geographical regions and different
      patient populations. The season of the year may also influence aetiology, and
      some infections follow a cyclical pattern. When an atypical pathogen is
      suspected, a macrolide antibiotic is an appropriate choice as, in addition to
      activity against these organisms, they are usually effective against the Gram
      positive and Gram-negative respiratory pathogens implicated in community-acquired
      pneumonia.

PMID- 11574198
TI  - Treatment of community-acquired pneumonia in hospitalised patients.
AB  - Community-acquired pneumonia (CAP) can be life-threatening. The prognosis is
      generally poorest in elderly patients and/or those with underlying chronic
      conditions, but fatalities can occur in all age groups. Current challenges in the
      clinical management of CAP are discussed, and the criteria for identifying those
      patients who should be treated in hospital with initial intravenous therapy are
      considered. Rapid initiation of therapy is important, using an agent that
      provides coverage against the most likely pathogens--Streptococcus pneumoniae and
      the atypical organisms. There is an increasing tendency to minimise the duration
      of intravenous therapy, with an early transition to oral therapy and the rapid
      return of the patient to the community. The efficacy of oral macrolides in the
      treatment of CAP is well established. Evidence for the use of intravenous
      azithromycin to provide effective and well-tolerated, first-line intervention in
      the hospitalized CAP patient is summarised.

PMID- 11574199
TI  - Comparative safety of the different macrolides.
AB  - The macrolides are generally well tolerated when used for the treatment of acute
      infections. Even when given long term for prophylaxis, there are few
      discontinuations due to side-effects. There are isolated reports of QT(c)
      prolongation in patients treated with erythromycin and other 14-membered-ring
      macrolides. Since the 14-membered-ring macrolides are metabolized by P450
      isoenzymes, there is the potential for interaction with other therapeutic agents
      also metabolized in this way. Pharmacokinetic studies have demonstrated
      interactions between either erythromycin or clarithromycin and cyclosporin,
      cisapride, pimozide, disopyramide, astemizole, carbamazepine, midazolam, digoxin,
      hydroxymethylglutaryl-coenzyme A reductase inhibitors (i.e. 'statins') and
      warfarin. In patients receiving such concurrent therapy, azithromycin may be
      superior to erythromycin and clarithromycin.

PMID- 11574200
TI  - Evaluation of the safety of macrolides.
AB  - The safety of all drugs is established by animal studies, administration to
      healthy volunteers and the observations during clinical studies to confirm
      efficacy. During these studies, patients are questioned about side-effects and
      extensive laboratory testing of blood and urine samples is performed. Despite
      these extensive studies, new problems may arise during post marketing
      surveillance which is designed to identify any rare side-effects. Today, all
      studies suggest that macrolides, and especially the more recently developed
      agents, are well tolerated. Some variations in tolerability may be due to the
      size of the macrocyclic ring and the presence of different esters. There are very
      few instances of irreversible organ damage.

PMID- 11574201
TI  - Diffuse panbronchiolitis--pathophysiology and treatment mechanisms.
AB  - Diffuse panbronchiolitis (DPB) is a chronic, potentially life-threatening lower
      respiratory tract disease that is particularly common in Japanese people. It is
      characterized by chronic infiltration of inflammatory cells, and Pseudomonas
      aeruginosa is isolated from sputum in some cases. Bronchoalveolar lavage fluid
      from DPB patients contains high concentrations of neutrophils, lymphocytes and
      inflammatory cytokines compared with levels found in other chronic lung diseases.
      If left untreated, DPB progresses rapidly and is usually fatal, but long-term,
      low-dose macrolide therapy improves the prognosis. Macrolides are effective
      against DPB even in the absence of a P. aeruginosa infection. There is evidence
      that these antibiotic agents may have an anti-inflammatory mode of action in DPB.

PMID- 11574202
TI  - Non-antimicrobial activities of macrolides.
AB  - While using macrolides for the treatment of infectious diseases, some non
      microbiological effects have been observed. The stimulation of gastrointestinal
      motility, which is a common side-effect of macrolides, may be advantageous in
      patients with poor upper gut motility. Macrolides, as well as directly inhibiting
      bacterial growth, may exert immunomodulatory effects. Utilisation of these
      properties may be useful in the treatment of chronic inflammatory conditions,
      especially if bacterial infection is also implicated. Preliminary evidence also
      suggests that the currently available macrolide antibiotics possess antitumour
      activity. In the future, an increased understanding of the structure-activity
      relationships of macrolides may result in the development of new structurally
      related compounds that concentrate on these pharmacological properties in
      addition to, or instead of, antimicrobial activity.

PMID- 11574203
TI  - New perspectives on macrolide antibiotics.
AB  - Macrolides are not used exclusively for the treatment of community-acquired
      respiratory tract infections. Their ability to penetrate cells makes them highly
      suitable for the treatment of diseases caused by intracellular pathogens, such as
      non-gonococcal urethritis and trachoma. Azithromycin is approved for these
      indications. Clinical studies have also been conducted, or are currently being
      carried out, to assess the use of macrolides in the treatment of atherosclerosis,
      eradication of Helicobacter pylori and the management of life-threatening
      gastrointestinal diseases, cystic fibrosis and malaria.

PMID- 11574205
TI  - Chestwall resection: a new and simple method for stabilization of extended
      defects.
AB  - OBJECTIVE: Postresectional chestwall defects can usually be stabilized by
      reconstructions under tension. Only few extended defects require combined
      stabilizing methods. The one used mostly is Marlex-Sandwich, despite some
      disadvantages. An alternative method using alloplastic material/metal bar is
      presented. MATERIAL AND METHODS: Between 1986 and 1999, 189 chestwall resections
      were performed either for infiltrating bronchogenic carcinoma (Type I, n=67),
      tumors originating from chestwall or bony metastases (Type II, n=88), or local
      recurrences and infiltration by breast cancer or sequelae of its treatment (Type
      III, n=34). The standard reconstruction is performed with non-absorbable
      alloplastic meshes or patches under some degree of tension. For defects exceeding
      250 cm(2), usually Type-II cases, a reconstruction under tension is no longer
      appropriate. Therefore we developed a procedure which we used in six cases.
      Alloplastic mesh or patch gets sutured in the same way as is done in smaller
      defects. Then a metal bar (Grob-Stab, Ulrich, Herrlingen/Blaustein, Germany) is
      threaded through the alloplastic material and is fixed at the adjacent ribs by
      Parham steel bands (Ethicon, Sommerville, KY, USA). RESULTS: In all cases we
      achieved excellent stability. All of the patients were extubated on the operating
      table. There was no morbidity or mortality. In three cases the metal bars were
      removed after 3, 6 and 16 months postoperatively (dynamization). CONCLUSION: The
      new procedure is safe, simple and quickly performed. The additional costs are low
      (160 euro). The patient's comfort is excellent; borderline problems as described
      for Marlex-Sandwich can be avoided, so that this procedure can be considered as
      an alternative to Marlex-Sandwich.

PMID- 11574204
TI  - Structure of general thoracic surgery in Europe.

PMID- 11574206
TI  - Outcome after unilateral lung volume reduction surgery in patients with severe
      emphysema.
AB  - OBJECTIVE: Bilateral lung volume reduction surgery (LVRS) has emerged as a
      palliative treatment option in patients with severe pulmonary emphysema. However,
      it is not known if a sustained functional improvement can be obtained using an
      unilateral approach. METHODS: We hypothesized that a palliative effect can also
      be obtained by unilateral LVRS and prospectively assessed lung function, walking
      distance, and dyspnea before and 3, 6, 12, 18, 24 and 36 months after unilateral
      LVRS. RESULTS: Twenty-eight patients were operated by the use of video-assisted
      thoracoscopic surgery (VATS) with a mean follow-up of 16.5 months (range 3-36
      months). Forced expiratory volume in 1 s (FEV1) was significantly improved up to
      3 months (1007+/-432 compared to 1184+/-499 ml, P<0.001), residual volume up to
      24 months (4154+/-1126 compared to 3390+/-914 ml, P<0.01), dyspnea up to 12
      months (modified Borg dyspnea scale 6.6+/-1.8 compared to 3.9+/-1.8, P=0.01) and
      walking distance up to 24 months (343+/-107 compared to 467+/-77 m, P<0.05) after
      unilateral LVRS compared to preoperative values. Overall, 25 of 28 patients
      reported a subjective benefit after unilateral LVRS. There was no 30-day
      mortality. Only two patients required surgery on the contralateral side after 4.5
      and 6 months, respectively, both suffering from alpha-1-antitrypsin deficiency.
      CONCLUSIONS: Unilateral LVRS by the use of VATS results in a sustained beneficial
      effect, improving walking distance and dyspnea for up to 24 months in patients
      with severe emphysema. The preservation of the contralateral side for future
      intervention if required renders unilateral LVRS an attractive concept in this
      difficult palliative situation.

PMID- 11574207
TI  - Wedge resection of the bronchus: an alternative bronchoplastic technique for
      preservation of lung tissue.
AB  - OBJECTIVES: We present a modified wedge resection of the bronchus, as an
      alternative bronchoplastic technique for lung resection, in cases of patients
      with or without adequate pulmonary reserve to undergo a pneumonectomy, in order
      to preserve lung tissue. METHODS: Seventeen patients underwent a major lung
      resection with wedge resection of the bronchus for non-small cell lung cancer
      (NSCLC) in our department, from March 1995 to October 1999. A right-sided NSCLC
      were diagnosed in 17 males, with a mean age 62.5+/-6.6 (range 51-72) years.
      Further workup was free of metastatic disease. All patients underwent a right
      posterolateral thoracotomy, under general anesthesia with a double lumen
      endotracheal tube. Twelve right upper lobectomies, four right upper and middle
      lobectomies and one carinal resection were performed. The wedge resection of the
      bronchus carried out longitudinally, along the bronchial tree, and the bronchial
      defect was reapproximated transversely, in a single-layer, with interrupted non
      absorbable suture. The frozen section of the distal margin of the resected
      bronchus was negative for malignancy in all patients. Extended mediastinal lymph
      node dissection followed each lung resection. RESULTS: The pathology report
      showed 12 squamous-cell carcinomas, three adenocarcinomas, one adenosquamous
      carcinoma and one neuroendocrine carcinoma. The differentiation of the carcinomas
      was well in two cases, moderate in ten and poor in five. The pTNM stage was IB in
      four patients (23.5%), IIA in one (5.9%), IIB in eight (47.1%) and IIIA in four
      (23.5%). The median disease-free distal margin of the bronchus was 5 mm (range 2
      15 mm). The average postoperative hospital stay was 15 days (range 12-28 days).
      The morbidity and mortality rate was 11.8 and 5.9%, respectively. Postoperative
      follow-up was every 6 months. The average survival is 20.0+/-15.2 months (range 1
      54 months). There are 12 patients alive, and their follow-up is negative for
      locoregional recurrence or distant metastasis. The survival study showed no
      significantly statistic relation to the histologic type, cancer differentiation,
      pTNM stage, and disease-free distal margin of resection larger or less than 0.5
      cm (Kaplan-Meier study log rank method). CONCLUSIONS: The wedge resection of the
      bronchus as a bronchoplastic procedure is an easy, fast and safe technique of
      reparation of the bronchial tree. It presents not only a low rate of morbidity
      and mortality, but also a satisfactory survival.

PMID- 11574208
TI  - Pulmonary lobectomy for lung cancer: a prospective study to compare patients with
      forced expiratory volume in 1 s more or less than 80% of predicted.
AB  - OBJECTIVE: To compare post-operative course, lung function and survival of lung
      cancer patients with a forced expiratory volume in 1 s (FEV1) more or less than
      80% of predicted submitted to lobectomy. METHODS: The data of patients undergoing
      lobectomy for non small cell carcinoma at the Thoracic Surgery Unit of the
      Ospedale Maggiore Policlinico of Milan, Italy, were prospectively collected.
      Inclusion criteria were a radical resectable tumor with size less than 2.5 cm,
      negative mediastinal nodes, capability to complete pulmonary function tests,
      Exclusion criteria were FEV1 <40% of predicted, pre- or post-operative chemo or
      radiotherapy, lobe to be resected receiving more than 30% of the perfusion,
      incapacity to quit smoking. RESULTS: Eighty-eight patients entered the study and
      were divided into two groups according to their FEV1%: 45 patients were included
      in control group (mean FEV1: 92.2%) and 42 in chronic obstructive pulmonary
      disease group (mean FEV1: 64.2%). Post-operative complications, operative
      mortality and actuarial survival were the same in the 2 groups. Six months after
      lobectomy, the mean changes in FEV1 were -14.9% for first group and -3.2% for
      second group (P<0.001). CONCLUSION: Lobectomy for cancer can be performed
      successfully also in selected patients with chronic obstructive pulmonary
      disease. Post-operative course and survival of these patients is not different
      from that of patients with normal FEV1, on the contrary, patients with low FEV1
      may lose less pulmonary function or even mend it.

PMID- 11574209
TI  - Supraventricular arrhythmias after resection surgery of the lung.
AB  - OBJECTIVE: Two hundred consecutive patients undergoing resection surgery of the
      lung during 1999 were retrospectively reviewed to define prevalence, type,
      clinical course and risk factors for postoperative supraventricular arrhythmias
      (SVA) with particular reference to atrial fibrillation or flutter (AF). METHODS:
      Records of 200 lung patients were collected and analysed with particular
      attention to preoperative physiologic values and associated pathologies, lung
      functional status, electrocardiogram registration, extent of surgical resection
      of the lung and were also analysed to confirm or exclude correlation between them
      and postoperative AF; three patients were excluded as they were affected
      preoperatively by SVA. RESULTS: Forty-five episodes of SVA, 41 of AF were
      identified in 197 patients (22%) and were more prevalent in several groups of
      patients such as those with increased age, pneumonectomy and superior lobectomy.
      Rhythm disturbances were most likely to develop on the second day after surgery.
      Ninety-eight percent of AF disappeared within a day of discharge and sinus rhythm
      was restored with digitalis or other antiarrhythmic drugs in all patients except
      one who was discharged with persistent atrial fibrillation. Arrhythmias were not
      direct causes of any in-hospital deaths. There is a tendency in the difference of
      the AF rate between pneumonectomy and upper lobectomy patients versus inferior
      lobectomy ones, probably related to the different anatomic structure of the
      proximal trunks of the upper and inferior veins of the lung, respectively.
      CONCLUSIONS: Statistical analysis revealed that increased age, extent and type of
      pulmonary resection, such as pneumonectomy and superior lobectomy were
      significant risk factors. Despite these factors, arrhythmias after lung surgery
      could be managed easily and were not closely related to higher mortality. Direct
      cause of AF after lung resection surgery remains unclear; anatomical substrate
      such as surgical damage to the cardiac plexus or to the proximal trunks of the
      pulmonary veins covered by myocardial sleeves with electrical properties are to
      be considered.

PMID- 11574210
TI  - Outcome after lung cancer surgery. Factors predicting early mortality and major
      morbidity.
AB  - OBJECTIVE: This study was undertaken to assess mortality, complications and major
      morbidity during the first 30 days after lung cancer surgery and to estimate the
      significance of presurgical risk factors. METHODS: The study was based on all
      patients referred for surgery for primary lung cancer from 1 January 1987 to 1
      September 1999. There were in total 616 patients with primary lung cancer. Three
      hundred and ninety-four were men and 222 women. Postoperative events studied were
      divided into major and minor complications or death during the first 30 days
      after surgery. The significance of risk factors for an adverse outcome (defined
      as death or major complication in the first 30 days postoperatively) was assessed
      by uni- and multivariate logistic regression analyses. RESULTS: During the study
      period an increasing number of women and of patients older than 70 years
      underwent surgery. Overall 30-day mortality was 2.9, 0.6% after single lobectomy
      and 5.7% after pneumonectomy. Major complications occurred in 54 patients (8.8%).
      Fifty-eight patients (9.5%) had an adverse outcome during the first 30 days. Male
      gender, smoker, FEV(1)< or =70% of expected value, squamous cell carcinoma and
      pneumonectomy were risk factors predicting adverse outcome in the univariate
      model. Pneumonectomy and FEV(1)< or =70%, were the only independently significant
      factors for adverse outcome. Only pneumonectomy was independently associated with
      an increased risk for early death. CONCLUSION: Our results show low mortality and
      morbidity after lung cancer surgery. However, patients with reduced lung capacity
      and those undergoing pneumonectomy should be treated with great care, as they run
      a considerable risk of major complications or death during the first 30 days
      postoperatively. Older age (>70 years) does not appear to be a contraindication
      to lung cancer surgery, but patients in this group should undergo careful
      preoperative evaluation.

PMID- 11574211
TI  - Morbidity after surgery for non-small cell lung carcinoma is not related to
      neoadjuvant chemotherapy.
AB  - OBJECTIVES: To compare postoperative morbidity and mortality rates in two groups
      of operated non-small cell lung carcinoma patients (NSCLC) with or without
      induction chemotherapy. METHODS: This is a case-control study on 42 cases and 42
      controls. Cases (Group A) underwent induction chemotherapy. Chemotherapy
      indications and regimens were variable. Control cases (Group B) were randomly
      selected among 494 NSCLC comparable patients operated on in the same period of
      time. The selection criteria for operation were the same in both groups.
      Dependent outcomes were operative death and complications. Independent selected
      variables were: age, co-morbidity, predicted postoperative FEV1% (1 s forced
      expiratory volume in percentage), type of surgery and clinical and pathological
      staging. All postoperative events and independent variables were prospectively
      registered. Chi-square and risk calculations on contingence tables and one-way
      ANOVA have been tested. RESULTS: Both series are comparable in demographics,
      preoperative variables and type of surgery. No mortality has been registered. In
      Group A, the overall morbidity was 26.2% (11 out of 42 cases), and in Group B,
      this was 42.9% (18 out of 42 cases; P=0.084). Morbidity was not related to the
      type of surgery (pneumonectomy vs. other; P=0.205 in Group A and P=0.08 in Group
      B). Pathological staging did not influence the postoperative outcome, either in
      Group A (P=0.72; odds ratio, 1.515; 95% confidence interval (CI), 0.375-6.122) or
      Group B (P=0.299; odds ratio, 0.4; 95% CI, 0.089-1.797). CONCLUSIONS: Induction
      chemotherapy in NSCLC has no influence on postoperative morbidity.

PMID- 11574212
TI  - Vocal cord dysfunction after left lung resection for cancer.
AB  - OBJECTIVES: To evaluate the prevalence, the impact-related postoperative
      complications and the risk factors of vocal cord dysfunction (VCD) after left
      lung resection for cancer. METHODS: From February 1996 to April 1999, a review of
      prospectively gathered data was performed on 99 consecutive patients who
      underwent a pneumonectomy (n=50) or a lobectomy (n=49) with a mediastinal lymph
      node dissection. A fiber optic laryngeal examination was performed preoperatively
      for all patients and within the first week postoperatively in patients with
      symptom(s) or sign(s) of VCD or respiratory complications. RESULTS: Thirty-one
      patients (31%) had a postoperative VCD (group VCD) and 68 (68%) did not (group
      non-VCD). Mortality rate was 19% in group VCD and 9% in group non-VCD (P=0.13).
      Group VCD patients developed more pulmonary complications (P=0.014) and cardiac
      complications (P<0.001) compared to group non-VCD patients. A higher rate of
      reintubation (P=0.005), pneumonia (P=0.06), arrhythmia (P=0.002), cardiac failure
      (P<0.001) was noticeable in group VCD and may account for the higher rate of
      complications in this group. Using multivariate analysis, preoperative
      radiotherapy (P=0.001) and pneumonectomy (P=0.008) were predictive of
      postoperative VCD. Hospital stay was 22+/-16 days in group VCD and 13+/-9 days in
      group non-VCD (P<0.002). CONCLUSION: VCD is a frequent event that can lead to
      dramatic pulmonary complications. We would recommend to track it and to treat it
      as early as possible.

PMID- 11574213
TI  - The potential role of bcl-2, bax, and Ki67 expression in thymus of patients with
      myasthenia gravis, and their correlation with clinicopathologic parameters.
AB  - OBJECTIVE: The aim of this study was to evaluate bcl-2, bax (apoptotic
      oncoproteins), and Ki67 (cell proliferation-marker) expression in thymus of
      patients with myasthenia gravis (MG) and to determine the potential correlation
      with clinicopathologic parameters. METHODS: The study was done on 38 patients (16
      males, 22 females; mean age 38+/-10 years) with MG who underwent modified maximal
      thymectomy (MMT). Clinical staging (Osserman classification) included stage I in
      three, IIA in 19, IIB in 13 and III in three. Microscopic examination of thymus
      showed thymic hyperplasia in 19, atrophy in eight, thymoma in nine and thymic
      carcinoma in two. On paraffin sections, the streptavidin-biotin technique, using
      antibodies to bcl-2, bax, and Ki67, was employed, and in situ hybridization with
      digoxigenin-labeled probes to bcl-2 and bax was performed. In addition, the
      apoptotic body index (ABI) was assessed via the TUNEL method. Staining results
      were correlated with clinicopathologic parameters. RESULTS: Bcl-2 expression was
      higher in hyperplasia and thymoma cases, compared to thymic carcinomas (P<0.001).
      Higher expression in carcinomas, compared to hyperplasia and thymomas, was
      observed for bax (P<0.001), Ki67 (P<0.001) and ABI (P<0.001). Statistical
      analysis demonstrated: (A) positive correlation of bax+ cells with MG stage
      (P<0.001), ABI and %Ki67+ cells with MG stage (P<0.001, respectively), %Ki67+ and
      %bax+ cells with ABI (P<0.05); and (B) reverse correlation between %bcl-2+ cells
      and MG stage (P<0.05). CONCLUSIONS: In patients with MG who underwent MMT, bcl-2,
      bax, and Ki67 expression correlates positively or reversibly with the microscopic
      findings of thymus. Increased apoptosis and proliferation accompany advanced
      disease stage and possible worse prognosis.

PMID- 11574214
TI  - Surgical intervention for pulmonary tuberculosis: analysis of indications and
      perioperative data relating to diagnostic and therapeutic resections.
AB  - OBJECTIVE: To analyze the data on patients operated on for pulmonary tuberculosis
      (TB) with (Group I) or without (Group II) a correct TB diagnosis and preoperative
      anti-TB treatment. METHODS: Between 1980 and 1997, 144 resections for TB (Groups
      I+II) were performed. The 80 patients in Group I underwent therapeutic
      resections: 32 cases involved recurrent cavities or tuberculomas, three involved
      post-TB bronchiectasis, 13 involved progression of cavities or tuberculomas, and
      32 involved persistent tuberculomas after 6 months of anti-TB therapy. The 64
      patients in Group II were operated on for a suspicion of malignancy in 49 cases,
      for cavitary lesions with haemophthysis in six cases, for multiple lesions in
      seven cases, and for recurrent hydrothorax in two cases. RESULTS: Groups I and II
      included 0 and five pneumonectomies, 32 and 29 lobectomies, 48 and 20 wedge
      resections, 0 and nine videothoracoscopic biopsies, and 0 and one hilar
      lymphadenectomy, respectively. In Groups I and II, the mean duration of
      postoperative hospitalization was 13.2 and 10.4 days, and the frequency of
      postoperative pneumothorax was 11.25 and 4.6%, respectively. The incidence of
      bronchopleural fistula was 1.25 and 0%, the mortality was 0 and 3.1%, and the
      morbidity was 53.7 and 35.9% in Groups I and II, respectively. Two patients with
      active disease died in Group II. Pathology demonstrated that the frequency of
      acid-fast bacilli in Groups I and II was 40 and 25%, respectively. CONCLUSIONS:
      Patients without a correct preoperative TB diagnosis underwent more extensive
      parenchyma resection. Postoperative complications increased when acid-fast
      bacilli were present. The lack of preoperative anti-TB treatment did not involve
      a higher risk of minor complications, but death occurred only in this group.

PMID- 11574215
TI  - Surgery for pulmonary aspergilloma in post-tuberculous vs. immuno-compromised
      patients.
AB  - OBJECTIVE: To compare the outcome of surgical resection for aspergilloma between
      patients with post-tuberculous complex and neutropenia. METHODS: We
      retrospectively reviewed our surgical experience with pulmonary resection for
      aspergilloma in 30 patients. Of the 20 patients with complex aspergilloma
      complicating healed tuberculosis (group 1), 14 were male and six were female with
      an average age of 54 years (SD 7). The indication for surgery was recurrent
      haemoptysis in all and there were 17 lobectomies, two pneumonectomies and one
      bilateral lobectomy. There were ten patients with acute myeloid or lymphoid
      leukemia (group 2), six male and four female with an average age of 26 years (SD
      4). Twelve lesions required lobectomy in eight and wedge excision in four.
      RESULTS: In group 1 there was one post-operative death (5%), in a patient with
      massive haemoptysis and completely destroyed lungs with bilateral upper lobe
      aspergilloma secondary to pneumonia. Morbidity accounted for 25% (five patients),
      two required re-exploration for bleeding, two had prolonged air leak more than 7
      days and one developed empyema. The later was treated with drainage and rib
      resection. One patient had recurrence of haemoptysis during the follow up period
      (mean 42 months). In group 2 there was no mortality or morbidity and six patients
      proceeded to bone marrow transplantation with no complication or recurrence.
      CONCLUSIONS: Surgical resection for pulmonary aspergilloma in selected patients
      provides the best chance of cure. Pulmonary resection for post-tuberculous
      complex aspergilloma is associated with higher morbidity than resection for
      immuno-compromised patients.

PMID- 11574216
TI  - Successful endoscopical sealing of malignant esophageotracheal fistulae by using
      a covered self-expandable stenting system.
AB  - OBJECTIVE: Any treatment of tracheo-esophageal fistulae in end-stage malignant
      stenosis of the esophagus must be weighed against associated morbidity and
      mortality. In a prospective study we investigated benefits and risks of the use
      of one type of coated, self-expandable stent. PATIENTS AND METHODS: We treated
      four male and two female patients, (mean age 68.3 years, range: 38-90 years),
      with malignant esophago-tracheal fistula non-resectable due to advanced tumour
      stage and/or functional reasons. All were in a poor general condition suffering
      from aspiration pneumonia and malnutrition. Four out of the six patients had had
      one or multiple extra- or endoluminal palliative treatments at a mean interval of
      191 days (range: 7 days-15 ms) since the last intervention. The fistulae were
      sealed by using a covered, self-expandable stent (ULTRAFLEX esophageal stent
      system, Microinvasive, Boston Scientific Corporation, Boston, MA). RESULTS:
      Stenting did not cause any technical problems and all fistulae were successfully
      sealed in a one-step procedure. The median hospital stay was 4.6 days (range: 3-9
      days). Except for one late stent induced recurrent fistula treated by re-stenting
      and tracheostomy, we did not observe any stent associated complications. Five
      patients died of tumour generalization. The median survival of the patients who
      died was 78 days (range: 35-129 days). One patient is alive and well at 120 days
      after stenting. CONCLUSION: In spite of the small number of patients the results
      suggest that this type of stent represents a safe and efficient approach for
      palliative endoscopic treatment of this high risk group. Local pretreatment does
      not preclude the successful use of the self-expandable coated stent.

PMID- 11574217
TI  - Descending necrotizing mediastinitis: surgical management.
AB  - OBJECTIVE: Descending necrotizing mediastinitis (DNM) is a primary complication
      of cervical or odontogenical infections that can spread to the mediastinum
      through the anatomic cervical spaces. METHODS: Between April 1994 and April 2000,
      13 patients, mean age 39.23+/-18.47 (median 38, range 16-67) years, with DNM were
      submitted to surgical treatment. Primary odontogenic abscess occurred in six,
      peritonsillar abscess in five and post-traumatic cervical abscess in two
      patients. Diagnosis was confirmed by computed tomography (CT) of the neck and
      chest. All patients underwent surgical drainage of the cervico-mediastinal
      regions by a bilateral collar incision associated with right thoracotomy in ten
      cases. RESULTS: Six patients out of 13 required reoperation. Two patients
      previously submitted only to cervical drainage required thoracotomy; four
      patients, which have been submitted to cervico-thoracic drainage, underwent
      contralateral thoracotomy in two cases and ipsilateral reoperation in two cases.
      Ten patients evolved well and were discharged without major sequelae; three
      patients died of multiorgan failure related to septic shock. Mortality rate was
      23%. CONCLUSION: Early diagnosis by CT of the neck and chest suggest a rapid
      indication of surgical approach to DNM. Ample cervicotomy associated with
      mediastinal drainage via large thoracotomic incision is essential in managing
      these critically ill patients and can significantly reduce the mortality rate for
      this condition, often affecting young people, to acceptable values.

PMID- 11574218
TI  - Aggressive primary treatment for poststernotomy acute mediastinitis: our
      experience with omental- and muscle flaps surgery.
AB  - OBJECTIVE: The surgical treatment of poststernotomy acute mediastinitis remains
      challenging. After disappointing results with a conservative management of post
      coronary artery bypass grafting (CABG) mediastinitis, we shifted towards a more
      aggressive surgical management. METHODS: From March 1993 until December 1999, 32
      patients (6 female/26 male), 0.5% of the total sternotomy population, were
      operated for mediastinitis, defined as wound and sternal dehiscence with
      medistinal pus and positive culture. Mean age was 66 years (32-79 years). Twenty
      two patients (75%) underwent CABG and 16 patients were in New York Heart
      Association (NYHA) class III/IV. RESULTS: We performed an omentoplasty in 11
      patients, a pectoralis muscle flap associated with an omentoplasty in 20
      patients. One patient had a bilateral pectoralis myoplasty. The reconstruction
      surgery occurred at an average of 11 days (6-26) after primary surgery. Twelve
      patients had a previous surgical drainage (1-3 surgical procedures) of the
      mediastinum. Hospital mortality was nine patients (28%). Seven of these patients
      (77%) were in NYHA IV with inotropic support. Five patients had to be reoperated
      on: four patients had a bilateral myoplasty after omentoplasty, one patient had
      an omentoplasty after a unilateral myoplasty. Late epigastric hernia was seen in
      three patients, two patients had wound revision and one had a retroperitoneal
      drainage for pancreatitis. There were no early or late flap failures. CONCLUSION:
      In our experience, omental and pectoralis flaps for poststernotomy acute
      mediastinitis provides good outcome of our stable patients. We would be reluctant
      to use it as standard therapy in our unstable patients.

PMID- 11574219
TI  - Urgent surgical revascularization of unstable angina. Influence of double mammary
      arteries.
AB  - OBJECTIVE: Aim of this study was to evaluate retrospectively: (1) the outcome in
      patients with unstable angina (UA) refractory to the medical therapy undergoing
      urgent-emergent CABG; (2) the influence of both IMAs employment. PATIENTS AND
      METHODS: Between January 1995 and July 2000, 576 (28.5%) consecutive patients
      with UA underwent CABG procedure. 182 (31.6%, Group I) patients, presenting
      unstable hemodynamic or angina pectoris refractory to the maximal medical
      therapy, underwent urgent/emergent CABG. 397 (68.4%, Group II) patients, after
      the maximal medical therapy did not present angina's episodes or ECG alterations
      and underwent elective CABG procedure. Preoperative data were similar in the two
      groups. Both IMAs were used in 68 (37.4%) patients of I and 152 (38%) of II
      (P>0.05) to left side revascularization. RESULTS: CAD extension was greater in
      Group I: 45 (24.7%) patients presented ischemia in >1 area vs 53 (13.5%) in II
      (P<0.001). Incidence of anteroseptal ischemia resulted significantly higher in I
      (P=0.017); left main coronary artery stenosis was present in 68 (37%) patients in
      I vs 108 (27%) in II (P=0.01). LV function resulted significantly depressed in I,
      demonstrated by a significantly lower LVEF (P<0.001), higher NYHA class (P<0.001)
      and preoperative incidence of IABP (P<0.001). Intraoperative data analysis did
      not reveal any difference between groups. Hospital mortality was 13 (7%) and 21
      (5.3%) patients in I and II respectively (P=ns). Multivariate analysis of all
      preoperative and intraoperative variables revealed the age >65 years (P=0.01),
      congestive heart failure (P<0.001), LVEF<35% (P=0.03), >1 ischemic area (P=0.02)
      as strong predictors for poor overall survival, and LIMA (P=0.006) and both IMAs
      (P=0.001) as strong predictors for good overall survival. Actuarial survival at
      1, 3 and 5 years resulted to be 98.5, 96.5 and 90% in I and 99, 96 and 92% in II
      (P=ns). CONCLUSION: CABG has been associated with acceptable outcome in patients
      with UA which should be applied soonest possible in patients refractory to
      medical treatment. Total coronary revascularization and employment of both IMAs
      for left myocardial side are associated with low operative risk and incidence of
      complications, permit to have acceptable short and long-term outcome in this pool
      of patients.

PMID- 11574220
TI  - Morphological differences of the internal thoracic artery in patients with and
      without coronary artery disease--evaluation by duplex-scanning.
AB  - OBJECTIVE: The internal thoracic artery is an established arterial graft for
      myocardial revascularisation, especially of the left anterior descending artery
      because of a higher patency rate compared to venous grafts. It has never been
      investigated, whether there are morphological differences in this vessel between
      patients with or without coronary artery disease or if they are comparable to
      morphological changes in the common carotid artery. METHODS: We investigated the
      internal thoracic artery and the common carotid artery of 24 patients (12 with
      coronary artery disease, 12 without coronary artery disease) with an ultrasonic
      system on both sides. The intima-media thickness and the diameter of both vessels
      were estimated. RESULTS: The intima-media-thickness of the internal thoracic
      artery was comparable in all patients, independent of the presence of a coronary
      artery disease (0.51+/-0.11 mm with coronary artery disease, 0.50+/-0.17 mm
      without coronary artery disease, P>0.05). Compared with this the intima-media
      thickness of the common carotid artery was thicker in patients with coronary
      artery disease (0.84+/-0.13 mm with coronary artery disease, 0.73+/-0.07 mm
      without coronary artery disease, P< or or =0.014). There was no correlation
      between the thickness of the internal thoracic artery and the common carotid
      artery (r=0.018, P>0.05). CONCLUSIONS: It could be demonstrated for the first
      with non-invasive ultrasound, that the intima-media-complex of the internal
      thoracic artery is protected of the influence of arteriosclerosis. There are no
      morphological differences like the intima-media-thickness of the common carotid
      artery. The proven protective mechanism underlines the widespread use of the
      internal thoracic artery as a coronary artery bypass graft.

PMID- 11574221
TI  - Beating heart coronary artery surgery: is sternotomy a suitable alternative to
      minimal invasive technique?
AB  - OBJECTIVES: To evidence the respective advantages and drawbacks of minimal
      invasive-thoracotomy (MIDCAB) and off-pump sternotomy (OPCAB) coronary bypass
      techniques. METHODS: The perioperative and mid-term (3 months) results of the
      first 31 MIDCABs and 39 OPCABs performed by a single experienced coronary surgeon
      (F.S.) were compared. Differences were assessed by two-tailed chi-square or
      unpaired t-test, and significance assumed for P-values < or =0.05. RESULTS:
      Groups were widely comparable. There were no in-hospital deaths nor permanent
      neurologic events. OPCAB patients received more anastomoses (mean 1.09/patient
      vs. 1.89/patient, P<0.001) during a shorter coronary occlusion period (26.1+/-8
      vs. 16.6+/-4.5min, P<0.001), whilst immediate extubation prevailed in MIDCABs
      (22/31 vs. 17/39, P<0.05). Significant complications occurred in seven MIDCABs
      vs. none in OPCABs (P<0.01). Other in-hospital parameters were similar. Controls
      at 3 months evidenced more residual discomfort among MIDCAB patients (14/30 vs.
      7/39, P<0.05). CONCLUSIONS: Differences in early complication rates may be due to
      a learning effect. However, OPCAB allows us to implant more grafts and is more
      comfortable for both patient and surgeon. These advantages may well
      counterbalance the cosmetic benefits of MIDCAB procedures.

PMID- 11574222
TI  - Technique of closed chest coronary artery surgery on the beating heart.
AB  - OBJECTIVE: The application of an endoscopic stabilizer (Intuitive Surgical,
      Mountain View, CA, USA) enables closed chest off-pump coronary artery bypass via
      a four-point stab incision avoiding sternotomy and minithoracotomy. METHODS:
      Between May 1999 and January 2001 we operated upon a total of 37 patients (five
      female, 32 male, median age 62+/-9 years) suffering from coronary artery disease
      using totally endoscopic coronary artery bypass (TECAB), whereas an initial
      series of eight TECAB patients was operated upon using an endovascular bypass
      system (Heartport). The da Vinci surgical system was used in order to perform
      left internal mammary artery (LIMA) or right internal mammary artery (RIMA)
      harvesting and anastomoses on a beating heart in 29 patients (four female, 25
      male, median age 64+/-9.8 years). Altogether 26 patients suffering from single
      vessel coronary artery disease (SVCAD) were revascularized applying LIMA to the
      left anterior descending artery (LAD) and three patients with two diseased
      coronary vessels received bilateral internal mammary artery grafting (BIMA),
      respectively. RESULTS: In this series we had a 100% survival rate. Conversion
      rate to a median sternotomy was 3.4%. Patients were operated upon via four 1-cm
      chest incisions using the da Vinci robot for LIMA or BIMA harvesting and for
      performance of anastomoses on the beating heart. In the overall series of 56
      patients intended to be treated by TECAB, 19 (33.9%) were converted to a
      minimally invasive direct coronary artery bypass procedure. CONCLUSION: This new
      robotic-enhanced surgical technique promotes an optimistic way of thinking about
      the further development of this procedure and its application in patients
      suffering from single-vessel CAD.

PMID- 11574223
TI  - Left ventricular dysfunction and disturbed O(2)-utilization in stunned
      myocardium: influence of ischemic preconditioning.
AB  - OBJECTIVE: Myocardial dysfunction during postischemic reperfusion is frequently
      reported only in terms of left ventricular (LV) systolic properties. We
      additionally assessed diastolic properties, the cardiovascular tone and in
      particular, the relation between ventricular function and myocardial oxygen
      consumption. Moreover, these measures are investigated after cardioprotection via
      ischemic preconditioning (IP). However, this phenomenon is not fully understood,
      and therefore cardioprotective methods like ischemic preconditioning might
      provide only insufficient protection. METHODS: In a total of 17 isolated rabbit
      hearts, perfused with an erythrocyte suspension (Hct 30%), we investigated the
      effect of 20 min low-flow ischemia also on diastolic properties, coronary
      resistance and cardiac energetics (n=9). During control and 30 min after the
      onset of reperfusion, LV systolic function was assessed in terms of aortic flow,
      dP/dt(max) and the end-systolic pressure-volume relation (ESPVR). Early
      relaxation was evaluated via dP/dt(min) and diastolic properties were assessed
      via the end-diastolic pressure-volume relation (EDPVR), i.e. using the equation
      LVP(ed)=c.exp(m.LVV(ed)), where c equals the LVP(ed)-axis intercept and m equals
      LV stiffness. In addition, coronary resistance (R(cor)) and the pressure-volume
      area (PVA) were calculated. Total oxygen consumption (MVO(2)) was calculated as
      well as the contractile efficiency (E = inverse slope of the MVO(2)-PVA
      relation). In a second series (n=8) the effect of ischemic preconditioning (3 min
      no-flow and 8 min reperfusion before the 20 min low-flow ischemia) was tested.
      RESULTS: In the first series, systolic function was impaired during reperfusion:
      aortic flow to 32% of control, dP/dt(max) to 74% and the slope of ESPVR to 73%.
      Early relaxation in terms of dP/dt(min) decreased to 76%. The slope of the EDPVR
      was steeper in stunned myocardium with an increase of the ventricular stiffness
      (m increased from 3.2 to 4.1) and with an upward shift of the EDPVR (c from 0.6
      to 2.4 mmHg). Coronary resistance was increased (from 0.9 to 1.4 mmHg/ml per min)
      and PVA was significantly decreased to 68%, whereas MVO(2) was not, indicating
      also a decrease in contractile efficiency E from 28 to 14%. In the second series,
      recovery of systolic function was significantly improved by IP compared with the
      first series (aortic flow 56% of preischemic control, dP/dt(max) to 91% and ESPVR
      to 78%). LV stiffness m was also slightly increased from 3.1 to 3.9 and again, c
      was elevated, indicating no beneficial effect for diastolic properties including
      dP/dt(min) (77%). But IP improved R(cor) significantly (from 0.9 to only 1.0
      mmHg/ml per min) and efficiency E to 21% (from 27% during control). CONCLUSION:
      Brief episodes of ischemia not only induce systolic but also diastolic and
      vascular stunning at almost maintained MVO(2). The decreased contractile
      efficiency clearly indicates an impaired O(2)-utilization of the contractile
      apparatus. Ischemic preconditioning did not improve diastolic function during
      reperfusion, but it provided protection with respect to vascular stunning and
      myocardial energetics.

PMID- 11574224
TI  - Preoperative modeling of an optimal left ventricle volume for surgical treatment
      of ventricular aneurysms.
AB  - OBJECTIVE: We evaluated the results of surgical treatment postinfarction
      ventricular aneurysms, with preoperative modeling of an optimal left ventricle
      volume. METHODS: From January 1998 to December 2000, 41 patients underwent left
      ventricular (LV) aneurysm repair. There were 39 men and two women, with a mean
      age 45.6+/-6.2 years. With echocardiography study, an optimal end-diastolic
      volume of LV was modeled on the basis of the proper stroke index and the
      contractile ejection fraction (EF). A permissible area of aneurysm resection was
      calculated by using a difference between the initial and the projected surface
      area of LV. The patch position and sizes were measured preoperatively.
      Ventricular reconstruction was performed by using linear plasty in eight
      patients, septal plasty of the Stoney et al. technique in 14 patients, and
      endoventriculoplasty of the Dor et al. technique in 19 patients. RESULTS: The
      mean NYHA functional class decreased from 2.9+/-0.6 to 1.6+/-0.7 postoperatively.
      The improvement of LV contracting function made itself evident in a decreased end
      diastolic volume from 216+/-98 to 158+/-35 ml, and end-systolic volume from 133+/
      85 to 80+/-34 ml postoperatively. The mean EF increased from 38+/-11 to 49+/-9%
      after operation. We noted that preoperative contractile EF corresponded with
      postoperative EF (49.8+/-11% and 49.3+/-9%, respectively). The projected optimal
      end-diastolic volume of LV estimated before operation agreed with postoperative
      data (152+/-33 ml and 158+/-35 ml, respectively). The hospital mortality rate was
      7.3%. CONCLUSIONS: Preoperative modeling of an optimal LV volume allows for the
      estimation of a permissible area of aneurysm resection, the position and sizes of
      the patch, as well as for the prevention of an excessive reduction of the LV
      cavity after aneurysm repair.

PMID- 11574226
TI  - Reshaping the remodelled left ventricle: a new concept.
AB  - OBJECTIVE: Based on the law of Laplace, transventricular tension members were
      designed to diminish wall stress by changing the left ventricle (LV) globular
      shape to a bilobular one, thus reducing the ventricular wall radius of curvature.
      This concept was tested in a model of congestive heart failure. METHODS: Seven
      calves were used for the study (74.3+/-4.2 kg). Treatment efficacy was assessed
      with sonomicrometric wall motion analysis coupled with intraventricular pressure
      measurement. Preload increase was applied stepwise with tension members in
      released and tightened position. RESULTS: Tightening of the tension members
      improved systolic function for CVP>10 mmHg (dP/dt: 828+/-122 vs. 895+/-112
      mmHg/s, P=0.019, for baseline and 20% stress level reduction respectively; wall
      thickening: 11.6+/-1.5 vs. 13.3+/-1.7%, P<0.001) and diastolic function (LV end
      diastolic pressure: 15.9+/-4.8 vs. 13.6+/-2.7 mmHg, P<0.001, for CVP>10 mmHg;
      peak rate of wall thinning: -12.2+/-2.2 vs. -14+/-2.3 cm(2)/s, P<0.001 and
      logistic time constant of isovolumic relaxation: 48.4 +/-10.9 vs. 39.8+/-9.6ms,
      P<0.001, for CVP>5 mmHg). CONCLUSIONS: This less aggressive LV reduction method
      significantly improves contractility and relaxation parameters in this model of
      congestive heart failure.

PMID- 11574225
TI  - Long term follow up of left ventricular function after repair of left ventricular
      aneurysm. A comparison of linear closure versus patch plasty.
AB  - OBJECTIVE: Suboptimal early and unsatisfactory late results after linear closure
      of left ventricular aneurysms, have focused attention on more physiologic
      concepts of aneurysmectomy, like endoventricular patch plasty. The aim of our
      study was to compare clinical results of linear closure and patch plasty 8 years
      after surgery. METHODS: From a total of 102 patients with postinfarctional left
      ventricular aneurysms, clinical outcomes and echocardiographic measurements of
      left ventricular function in 32 patients who underwent linear closure were
      compared to those of 20 patients who had endoventricular patch plasty. RESULTS:
      The two groups were matched with respect to age, gender, comorbid risk factors,
      functional class, urgency of the operation and concomitant procedures. In the
      patch plasty group, ejection fraction increased from 33.1+/-12.2% to 34.4+/-9.7%.
      In the linear closure group, ejection fraction decreased from 44.3+/-10.9% to
      40.1+/-7.9%. Perioperative mortality and complications, long term survival and
      functional class were similar in both groups with a total perioperative mortality
      of 1.9%, an 8-year survival rate of 85.6%, and a mean NYHA functional class of
      2.51. CONCLUSION: Long-term follow up showed a decline in ejection fraction in
      the direct closure group and a slight increase in the patch plasty group. We
      suggest that linear closure should be limited to small ventricular aneurysms and
      that large ventricular aneurysms extending into the septum should be treated by
      patch plasty.

PMID- 11574227
TI  - Two-decade analysis of cardiac storage for transplantation.
AB  - OBJECTIVE: Cardiac storage solutions and methods remain unstandardized. We have
      surveyed the literature to establish how the subject has progressed, addressing
      models of preservation and measures of outcome. Since a lot of the literature on
      cardiac storage is generated in the laboratory, we were particularly interested
      to evaluate to what extent bench work finds its way into and clinical practice.
      The discussion focuses in addition to new areas of research and introduces the
      concept of integrated organ preservation. METHODS: Five representative journals
      (J Thorac Cardiovasc Surg, Circulation, J Heart Lung Transplant, Eur J Cardio
      thorac Surg and Ann Thorac Surg) were searched by hand for papers published
      between 1980-1999. All laboratory, animal experimental and clinical studies
      focused on prolonged cardiac preservation and storage were selected. RESULTS: Two
      hundred and forty-nine publications were identified using preset criteria. Of
      these, 196 (79%) were studies performed in animal models and 10 (4%) were
      experiments carried out on animal tissue. One hundred and five experiments (42%
      of all studies) were performed in small animals. The most common animal model was
      of ischemia followed by ex vivo reperfusion (121 studies, 49% of publications).
      The measures of outcome were classified as biochemical, functional, morphologic
      and endothelial; the majority of studies had one (48%) or two (40%) end-points.
      Twenty-five studies (10%) had endothelial measures of outcome, alone or in
      combination with other types of outcomes. Human clinical work was represented by
      34 (14%) studies of clinical transplantation and nine (4%) experiments on human
      tissue only. There were five randomized clinical trials, representing 2% of all
      papers and 15% of all clinical research. CONCLUSION: In conclusion, most of the
      surgical publications on prolonged cardiac preservation result from animal
      research. Small animal models of ex vivo ischemia and reperfusion are
      predominant.

PMID- 11574228
TI  - Pneumocystis carinii pneumonia in heart transplant recipients.
AB  - OBJECTIVES: In spite of the high prevalence of Pneumocystis carinii (PC)
      pneumonia in immunocompromised patients, little is known about the
      epidemiological characteristics of this infection, and whether the cases of PC
      pneumonia in immunosuppressed patients are the result of a reactivation of a
      latent infection or a due to a recent infection is unknown. The aim of this study
      was to provide information about the epidemiological characteristics of PC
      pneumonia in a cohort of heart transplant (HT) recipients when compared with the
      epidemiology of PC infection in a cohort of chronic sputum producers (CSP)
      representative of the general population of the same geographical area. METHODS:
      We identified all the cases of PC pneumonia in the cohort of 72 subjects who
      underwent cardiac transplantation at our institution between January 1991 and
      December 1996 and compared them with the cases of PC infection identified in a
      non-selected cohort of 34 CSP. This second group was included to obtain an
      approximation of the frequency of PC carriers in the general population.
      Identification of PC was accomplished through customary stain techniques and
      immunofluorescence with monoclonal antibodies. RESULTS: Of the 72 HT recipients
      four (5.5%) developed PC pneumonia, but one had two episodes. Only one had
      received primary chemoprophylaxis, but developed PC pneumonia 2 months after
      discontinuing prophylactic therapy. PC pneumonia episodes were produced 53, 102,
      230, 181 and 772 days after the moment of transplant, respectively. PC was
      identified in two (5.8%) of the 34 CSP. No significant differences were found
      when the accumulative incidences of PC pneumonia in HT patients and PC infection
      in CSP were compared (P=0.7). CONCLUSIONS: The frequency of PC pneumonia among HT
      patients is the same as the frequency of PC infection in the general population.
      This observation and the long interval between transplantation and the
      development of PC pneumonia observed in the study support the hypothesis that the
      occurrence of PC pneumonia in immunocompromised patients might be from a new
      infection rather than from the reactivation of latent organisms. Therefore,
      continuous prophylaxis might be indicated in areas with a high prevalence of PC
      for patients at highest risk.

PMID- 11574229
TI  - Determinants of mortality after hypothermic circulatory arrest in a chronic
      porcine model.
AB  - OBJECTIVE: Beside neurological morbidity, mortality is a relevant end-point of
      experimental porcine model of hypothermic circulatory arrest (HCA) and this study
      was conducted to identify the determinants for postoperative death. METHODS: One
      hundred and thirty-five pigs underwent a 75-min period of HCA at 20 degrees C to
      evaluate the efficacy of different methods of cerebral protection. RESULTS:
      Survival rate at 7-day follow-up was 52%. Lower oxygen extraction, oxygen
      consumption/kg, and venous lactate at the end of cooling and higher oxygen
      delivery rates were significantly associated with better outcome. Logistic
      regression showed that the oxygen consumption/kg at the end of cooling was the
      only predictor of mortality (P=0.046). Animals with an oxygen consumption/kg rate
      less than 1.43 ml/min per kg at the end of cooling had a mortality rate of 28%,
      whereas it was 50% among animals with an oxygen consumption/kg rate higher or
      equal to 1.43 ml/min per kg (P=0.020). The latter had even an increased 1-day
      mortality rate (40% vs. 26%) (P not significant). The mortality rate after
      anesthesia induction with ketamine plus 100% of oxygen was 38%, 45% after
      anesthesia induction with ketamine plus 35% oxygen, and 53% after anesthesia with
      medetomidine plus 35% oxygen (P not significant). CONCLUSIONS: Parameters of
      oxyhemodynamics should be monitored especially from the induction of anesthesia
      to the end of cooling before a 75-min period of HCA. The use of medetomidine
      and/or 35% of oxygen at induction of anesthesia should be avoided in favor of
      ketamine plus 100% of oxygen.

PMID- 11574231
TI  - Transposition of the great arteries associated with ventricular septal defect:
      surgical results and long-term outcome.
AB  - OBJECTIVES: To identify potential risk factors influencing early and late outcome
      following the arterial switch operation (ASO) for transposition of the great
      arteries associated with ventricular septal defect including double-outlet right
      or left ventricle. METHODS: All patients who underwent ASO in our department
      until August 2000 (n=105) were included in this study. There were 77
      transpositions of the great arteries with ventricular septal defect, 22 Taussig
      Bing hearts and six patients with double-outlet morphology. The median age at
      operation was 24 days. Aortic arch obstruction was present in 25 patients; in 13
      of these patients, a repair with aortic arch reconstruction was done before ASO.
      The usual coronary artery pattern was present in 59% of the patients. In six
      patients, we found an intramural course of at least one coronary artery. The
      ventricular septal defect was closed with a patch through the right atrium
      (n=35), the aorta (n=25), the pulmonary artery (n=25) or the right ventricle
      (n=3); in 17 patients a combined approach was necessary. RESULTS: There were five
      hospital deaths (4.7%, 95% confidence limit 2-11%). The median duration of follow
      up was 72 months. Fourteen patients underwent 15 reoperations 33 months after
      repair (median), eight for right ventricular outflow tract obstruction or
      neopulmonary stenosis. Four late deaths occurred, two due to complications
      related to coronary artery anomalies. Statistical analysis revealed no
      significant risk factor whatsoever correlating with death or need for
      reoperation. Survival after 12 years was 91.6%, and freedom from reoperation was
      82.6%. Latest follow-up data showed that 13% of patients were in NYHA class II
      and/or required medical treatment; 87% were in NYHA class I. CONCLUSIONS: ASO
      associated with patch closure of ventricular septal defect can be performed early
      in life with a low risk of mortality (<5%), low incidence of reintervention
      (<15%) and promising long-term outcome.

PMID- 11574230
TI  - Post-cardiotomy mechanical circulatory support using a conventional bypass
      circuit in children.
AB  - OBJECTIVE: Mechanical circulatory support (MCS) is increasingly used after
      cardiotomy in children when conventional medical treatment fails. Poor overall
      survival and long-term outcome have been reported. We report our experience of
      post-cardiotomy MCS using a conventional bypass circuit. METHODS: Over a 4 year
      and 6 month period 10 patients, with a median age of 16 days (range 5 days to 16
      years) required MCS. Eight patients required support for failure to wean from
      cardiopulmonary bypass during primary correction. Two patients required support
      for cardiac arrest or poor cardiac output in the postoperative period. RESULTS:
      The median duration of support was 43 h (range 26-146 h). Seven hospital
      survivors were alive and well at median follow-up of 18 months (range 4-36
      months). One patient could not be weaned off support. Two more patients died
      after successful weaning from support. Complications in nine patients who could
      be weaned off support included renal failure (n=6), cerebrovascular events (n=3)
      and mediastinitis (n=2). CONCLUSIONS: Overall long-term survival (70%) and
      quality of recovery is usually good even though initial mortality and
      complication rates may be high. We think that post cardiotomy mechanical
      circulatory bypass using a conventional bypass circuit can offer a favourable
      outcome to selected patients.

PMID- 11574232
TI  - Surgical management and indication of left ventricular retraining in arterial
      switch for transposition of the great arteries with intact ventricular septum.
AB  - OBJECTIVE: Arterial switch is the operation of reference for the surgical
      treatment of transposition of the great arteries. In cases of late referral,
      perinatal complications or early left ventricular (LV) dysfunction, the one stage
      arterial switch is contra indicated. Anatomical repair remains possible in these
      patients following a LV retraining. METHODS: From January 1992 to January 2000, a
      LV retraining was attempted in 22 patients with transposition of the great
      arteries with intact ventricular septum (TGA IVS), whereas 470 direct arterial
      switch and 2 Senning were performed. Indication for LV retraining was based on a
      combination of factors including: an age older than 3 weeks, a "banana shape"
      aspect of the inter-ventricular septum and mainly a LV mass <35G/m(2). RESULTS:
      The mean age at LV retraining was 3.2 months ranging from 9 days to 8 months.
      Usually conducted by sterntomy, it associated a loose PA banding with a LV/RV at
      65% with a systemico-pulmonary shunt. The first stage was associated with
      frequent LV dysfunction and the LV retraining was discontinued in two patients in
      favor of one Senning and one early switch followed by ECMO. One patient died at
      first stage from a mediastinitis. Nineteen patients underwent a second stage
      arterial switch that was performed when the LV mass had reached 50 G/m(2) after a
      mean delay of 10 days, ranging from 5 days to 6 weeks. After a mean follow up of
      25 months, there was one non-cardiac late death. The 17 patients followed and
      leaving with an arterial switch are in NYHA class I, with a mean LV shortening
      fraction of 39%. CONCLUSIONS: Arterial switch following LV retraining in TGA IVS
      is a satisfactory option. The inferior limit of 35 G/m(2) adopted, to indicate LV
      retraining, seems a safe landmark. The quality of the myocardium generated and
      the respective roles played by the LV afterload, LV wall shear stress, LV inflow
      and outflow to induce the LV remodeling remain under debate.

PMID- 11574233
TI  - The beneficial hemodynamic effects of selective patent vertical vein following
      repair of obstructed total anomalous pulmonary venous drainage in infants.
AB  - OBJECTIVES: Postoperative low cardiac output may persist after repair of total
      anomalous pulmonary venous drainage (TAPVD) because of a relatively small and non
      compliant left atrium and left ventricle. We examined the effects of selective
      vertical vein patency on postoperative hemodynamics. METHODS: Thirty-four
      patients less than 3 months of age with TAPVD were operated from July 1993 to
      June 2000. The mean age at operation was 21+/-8 days (range, 3-62 days) and the
      mean weight was 3+/-0.2 kg (range, 2-4.1 kg). Supracardiac type drainage was
      found in 12 (35%), cardiac in three (9%), mixed in one (3%), and infracardiac in
      18 (53%) patients. Twenty-two patients (65%) had obstructed venous drainage. All
      operations were performed with deep hypothermic circulatory arrest. Supracardiac,
      mixed and infracardiac types were repaired through a posterior approach, whereas,
      in the cardiac type, the coronary sinus was unroofed and the atrial septal defect
      was patched. The decision whether to keep the vertical vein open was made at the
      end of the operation and was based on the hemodynamic state of the patient.
      RESULTS: There were no operative deaths. The suture on the vertical vein was
      released in 22 patients who had obstructed pulmonary venous drainage
      (infracardiac type, n=18; supracardiac type, n=3; and mixed type, n=1), resulting
      in a significant drop in the left atrial pressure from 19+/-2 to 12+/-2 mmHg
      (P<0.05), and in the mean pulmonary artery pressure from 42+/-6 to 35+/-3 mmHg
      (P<0.05), associated with an immediate increase in the mean arterial blood
      pressure from a mean of 46+/-3 to 60+/-4 mmHg (P<0.05). During a mean follow-up
      of 38+/-6 months (range, 8-71 months), there were no late deaths. Follow-up, two
      dimensional echocardiography with Doppler studies demonstrated good left
      ventricular function and trivial or no left to right shunt through the vertical
      vein in those patients in whom the snare was released. CONCLUSIONS: Maintaining
      the vertical vein patent in a selective group of patients with infracardiac total
      anomalous venous drainage contributes to a favorable outcome following surgery.

PMID- 11574234
TI  - Geometric mismatch between homograft (allograft) and native aortic root: a 14
      year clinical experience.
AB  - OBJECTIVES: We evaluated the effect of homograft/native aortic root geometric
      matching and mismatching on valve survival and myocardial remodeling. METHODS:
      Between January 1, 1987 and March 2000, a total of 292 patients, aged 1.5-78
      years (mean, 46.2 years), underwent freehand subcoronary aortic valve (AVR;
      n=207) and root (ARR; n=85) replacement with matched and mismatched cryopreserved
      homografts. All patients had pre- and postoperative two-dimensional Doppler
      echocardiographic studies. Two-hundred and forty-three survivors, excluding
      children with complete data on sizing, were followed at a total follow-up time of
      1269 patient-years. Seventy percent received matched and 30% received mismatched
      aortic homografts. The homograft valve sizes ranged from 19 to 28 mm. RESULTS:
      Hospital death for elective first operation was 2.3%, and late death after a mean
      follow-up of 52 months was 7.9%. The patient survival at 14 years was 92+/-2%. By
      linear regression analysis, matched homografts were equal to or 1-2 mm less than
      the native aortic annulus (r(2)=0.73). The valve survival in patients with AVR
      and ARR was 72+/-4 and 80+/-8% at 14 years, respectively. The freedom from
      reoperation was 92+/-5, 77+/-4 and 48+/-10% at 14 years for matched, oversized
      and undersized homografts, respectively (P=0.001). The postoperative cardiac
      index of patients with 22 and 24 mm homografts was 3.8-4.1 l/m(2), and there was
      a regression of the left ventricular mass and end-diastolic diameter (P=0.001).
      CONCLUSIONS: The aortic homograft offers an excellent long-term clinical result.
      A mismatched homograft is a risk factor for postoperative aortic incompetence,
      reinfection with pseudoaneurysmal formation and reoperation for the freehand
      subcoronary implantation technique during the first 7 years of the postoperative
      period. It is prudent therefore to avoid mismatched homografts and use rather a
      properly sized stentless xenograft if a root replacement is not indicated.

PMID- 11574235
TI  - Long-term results of multivalve surgery for infective multivalve endocarditis.
AB  - OBJECTIVE: The natural history of medically treated multivalvular endocarditis is
      associated with dismal short and long term survival. However, the impact of
      surgical intervention on these results is relatively unknown. The objective of
      this retrospective study was to report our long-term results in patients
      requiring multivalve surgery for multivalvular endocarditis. METHODS AND RESULTS:
      Over a 24 year period beginning in 1972, multivalve surgical procedures were
      performed on 63 patients for infective endocarditis. Prosthetic valve
      endocarditis was present in 25 (40%), and acute or active endocarditis in 38
      (60%). The early mortality was 16%. Out of 53 patients discharged from the
      hospital 87+/-4% were alive at 5 years and 64+/-9% at 10 years. There was no
      difference in early or late mortality between patients with prosthetic and native
      endocarditis (P=0.15 and P=0.77 for early and late mortality, respectively). The
      presence of active endocarditis did not affect operative outcome or late
      mortality. Twenty-one patients (88%) were in NYHA FC I, and none were in NYHA FC
      IV. The only prognostic factor of early and late mortality was the presence of an
      abscess at the time of the surgery. CONCLUSIONS: These results indicate that
      multivalve infective endocarditis treated surgically is associated with
      acceptable early and late mortality and excellent postoperative functional
      status. The early surgical intervention prior to an abscess formation offers the
      best chance for survival of patients with multivalve endocarditis.

PMID- 11574236
TI  - False aneurysm of ascending aorta-anastomosis after orthotopic heart
      transplantation.

PMID- 11574237
TI  - Superior vena caval obstruction by myxoma.

PMID- 11574238
TI  - Aneurysm of the cardio-hepatic segment of the inferior vena cava.

PMID- 11574239
TI  - Surgical repair of coronary arteriovenous fistula: a simple and useful approach
      to identify the fistulous communication.
AB  - In repairing coronary arteriovenous fistula (CAVF), it is very important to
      interrupt the fistulous tract without compromise of normal coronary vessel flow.
      In our case, selective coronary arteriography showed that the CAVF from the left
      anterior descending coronary artery (LAD) was very close to the native coronary
      artery and had a very broad and short neck. We describe a simple and useful
      approach, by using both antegrade and retrograde coronary perfusion, that makes
      it possible to certainly protect myocardium and to clearly distinguish the normal
      native coronary artery from the fistulous tract.

PMID- 11574240
TI  - Anomalous left coronary artery from the pulmonary artery: creating an autogenous
      arterial conduit for aortic implantation.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery requires
      surgical correction. A surgical technique is presented. Two infants underwent re
      implantation of their anomalous left coronary arteries by creating a tunnel using
      autogenous aortic and pulmonary arterial walls. The advantage of this technique
      is that the new left coronary artery lies in the horizontal plane and in an
      anatomically correct axis running in the groove behind the pulmonary artery. It
      also provides a tension free endothelialized autogenous arterial walls with
      normal growth anticipated.

PMID- 11574241
TI  - Thoracoscopy for minimally invasive axillo-coronary artery bypass.
AB  - Minimally invasive axillo-coronary artery bypass via a small thoracotomy or a
      limited sternotomy was performed in five patients. For this approach, videoscopy
      was used to determine the intrapleural path of each vein graft, which was curved
      by the expanded lung tissue and had the potential for kinking or distortion.
      Postoperative angiography confirmed the patency of each graft with no kinking or
      distortion. Thoracoscopy facilitates this approach, allowing appropriate
      placement of the vein graft in the chest cavity.

PMID- 11574242
TI  - Thoracic epidural anesthesia for off-pump coronary artery bypass without
      intubation.
AB  - Thoracic epidural anesthesia without intubation was used in 10 patients
      undergoing off-pump coronary artery reconstruction performed through median
      sternotomy. Considering the preoperative finding of impaired pulmonary function,
      all were moderate-risk patients for surgery using conventional general anesthesia
      with intubation. All patients had an uneventful postoperative course. In
      indicated cases, we regard thoracic epidural anesthesia as a suitable method
      again modifying the term "minimally invasive" in cardiac surgery.

PMID- 11574243
TI  - Concurrent cysts of the mediastinum, pleura and neck.
AB  - A 14-year-old male was found to have a mediastinal mass on chest radiograph.
      Chest computed tomography scans showed a cystic lesion behind the left main
      bronchus. Magnetic resonance imaging revealed additional cystic lesions in the
      left chest and root of the neck. He underwent excision of mediastinal mass and a
      pleural cyst. The neck lesion was presumed to be a cystic hygroma. Histological
      examination of the two lesions resected showed them to be a foregut cyst and a
      benign mesothelial cyst. We know of no other report of concurrent multicystic
      lesions in the chest and neck and hypothesize that these cysts may have a common
      embryonic origin.

PMID- 11574244
TI  - Primary malignant melanoma of the lung in oculocutaneous albino patient.
AB  - Oculocutaneous albinism is a rare autosomal recessive disorder characterized by
      general depigmentation, nystagmus, photophobia, and decreased visual acuity.
      Malignant melanoma is extremely rare in patients with albinism. We present a 41
      year-old albino male patient, who was admitted with a suspected bronchogenic
      carcinoma. He underwent a pulmonary resection and the diagnosis was primary
      malign melanoma of the lung. The patient died of tumor recurrence in the
      postoperative 46th month.

PMID- 11574245
TI  - Implantation metastasis caused by fine needle aspiration biopsy following
      curative resection of stage IB non-small cell lung cancer.
AB  - Fine needle aspiration is a useful procedure in the diagnosis of lung cancer,
      however controversy still remains as to whether it should be employed
      particularly in patients with operable lung cancer. We report herein a case of
      metastatic tumor at the site of transthoracic needle biopsy following a curative
      resection in a patient with stage IB bronchogenic carcinoma. The patient was
      managed with aggressive chest wall resection and subsequent musculocutaneus flap
      transposition, however he died 11 months after the initial operation. The tumor
      implantation risk and the related complications should be considered in patients
      with operable bronchogenic carcinoma undergoing a tranthoracic needle aspiration
      biopsy.

PMID- 11574246
TI  - Vascular amyloidosis causing spontaneous mediastinal haemorrhage with
      haemothorax.
AB  - Bleeding diathesis is a recognised complication of amyloid disease. Localised and
      generalised bleeding manifestations are usually associated with intravascular
      coagulopathy related to isolated or multiple coagulation factor deficiencies.
      Recently, there have been reports of haemorrhage due to amyloid deposition in
      blood vessel walls and in the perivascular region leading to increased fragility
      and poor haemostasis. We report a case of spontaneous mediastinal haemorrhage due
      to amyloid involvement of vascular tissue in the absence of coagulopathy.

PMID- 11574247
TI  - Post-pneumonectomy video-assisted thoracoscopic bullectomy using extra-corporeal
      membrane oxygenation.
AB  - We describe a case of a patient who, 14 years after a pneumonectomy, required
      surgery for a life-threatening air-leak following accidental intubation of an
      emphysematous bulla in his remaining lung. To facilitate treatment by video
      assisted thoracoscopic surgery, veno-venous extra-corporeal membrane oxygenation
      was employed.

PMID- 11574248
TI  - Renal carcinoma with caval vein infiltration and triple coronary disease: one
      stage surgical management.
AB  - We report the one-stage surgical management in a 68-year-old patient with a renal
      cell carcinoma with extended intravascular growth into the inferior vena cava
      combined with severe triple coronary artery disease. After nephrectomy the
      resection of the intravascular tumor and caval reconstruction were performed in
      deep hypothermic circulatory arrest. Coronary revascularization was accomplished
      while rewarming. The postoperative course was uneventful. Nine months after this
      operation there are no signs of reoccurrence.

PMID- 11574249
TI  - Resolution of an aortic thrombus under anticoagulant therapy.
AB  - In a 50-year-old woman, admitted because of a renal infarction, a 10-cm long
      floating, highly mobile thrombus with a diameter of 15-20 mm in the descending
      aorta was detected by transoesophageal echocardiography and magnetic resonance
      imaging. She was a poor surgical candidate due to obstructive lung disease and
      obesity. Under intravenous heparinization with prothrombin time test values
      between 80 and 100 s, followed by oral anticoagulation with international
      normalized ratio values between 3.0 and 4.0, the thrombus resolved after 10 weeks
      and no recurrence occurred over the next 30 months.

PMID- 11574250
TI  - Ischemic heart disease associated with protein C deficiency.
AB  - Three patients of ischemic heart disease associated with protein C deficiency are
      reported. Although delayed diagnosis of protein C deficiency resulted in the
      failure of repeated interventions, coronary artery bypass grafting performed
      after making the correct diagnosis has led to satisfactory mid-term results under
      strict anticoagulation therapy. The level of protein C should be measured more
      frequently in the field of ischemic heart disease and earlier diagnosis of its
      deficiency should be made, because measurement of protein C does not cost much.

PMID- 11574251
TI  - Endoventricular circular patch plasty for end-stage valvular cardiomyopathy.
AB  - We present here a case of end-stage non-ischemic valvular dilated cardiomyopathy
      (DCM) associated with mitral regurgitation (MR). The patient underwent surgery
      where left ventricular volume reduction using endoventricular circular patch
      plasty (EVCPP) and mitral valve replacement (MVR) were performed. He has improved
      much after the operation and is now in New York Heart Association (NYHA)
      functional class II.

PMID- 11574252
TI  - Chaos in the brain: a short review alluding to epilepsy, depression, exercise and
      lateralization.
AB  - Electroencephalograms (EEGs) reflect the electrical activity of the brain. Even
      when they are analyzed from healthy individuals, they manifest chaos in the
      nervous system. EEGs are likely to be produced by a nonlinear system, since a
      nonlinear system with at least 3 degrees of freedom (or state variables) may
      exhibit chaotic behavior. Furthermore, such systems can have multiple stable
      states governed by "chaotic" ("strange") attractors. A key feature of chaotic
      systems is the presence of an infinite number of unstable periodic fixed points,
      which are found in spontaneously active neuronal networks (e.g., epilepsy). The
      brain has chemicals called neurotransmitters that convey the information through
      the 10(16) synapses residing there. However, each of these neurotransmitters acts
      through various receptors and their numerous subtypes, thereby exhibiting complex
      interactions. Albeit in epilepsy the role of chaos and EEG findings are well
      proven, in another condition, i.e., depression, the role of chaos is slowly
      gaining ground. The multifarious roles of exercise, neurotransmitters and
      (cerebral) hemispheric lateralization, in the case of depression, are also being
      established. The common point of reference could be nonlinear dynamics. The
      purpose of this review is to study those nonlinear/chaotic interactions and point
      towards new theoretical models incorporating the oscillation caused by the same
      neurotransmitter acting on its different receptor subtypes. This may lead to a
      better understanding of brain neurodynamics in health and disease.

PMID- 11574253
TI  - A model of neonatal tidal liquid ventilation mechanics.
AB  - Tidal liquid ventilation (TLV) with perfluorocarbons (PFC) has been proposed to
      treat surfactant-deficient lungs of preterm neonates, since it may prevent
      pulmonary instability by abating saccular surface tension. With a previous model
      describing gas exchange, we showed that ventilator settings are crucial for CO(2)
      scavenging during neonatal TLV. The present work is focused on some mechanical
      aspects of neonatal TLV that were hardly studied, i.e. the distribution of
      mechanical loads in the lungs, which is expected to differ substantially from gas
      ventilation. A new computational model is presented, describing pulmonary PFC
      hydrodynamics, where viscous losses, kinetic energy changes and lung compliance
      are accounted for. The model was implemented in a software package (LVMech) aimed
      at calculating pressures (and approximately estimate shear stresses) within the
      bronchial tree at different ventilator regimes. Simulations were run taking the
      previous model's outcomes into account. Results show that the pressure decrease
      due to high saccular compliance may compensate for the increased pressure drops
      due to PFC viscosity, and keep airway pressure low. Saccules are exposed to
      pressures remarkably different from those at the airway opening; during
      expiration negative pressures, which may cause airway collapse, are moderate and
      appear in the upper airways only. Delivering the fluid with a slightly smoothed
      square flow wave is convenient with respect to a sine wave. The use of LVMech
      allows to familiarize with LV treatment management taking the lungs' mechanical
      load into account, consistently with a proper respiratory support.

PMID- 11574254
TI  - Peristaltic flow in a tapered channel: application to embryo transport within the
      uterine cavity.
AB  - Cyclic uterine peristalsis plays a central role in assisting the transport of
      sperm to the fallopian tube and later in the conception process in transporting
      the embryo to a fundal site for implantation. Fulfillment of these essential
      events within the time limits of fertilization and implantation depends on
      concomitant intrauterine fluid motion induced by uterine wall motility. A model
      of wall-induced fluid flow within a finite tapered two-dimensional channel was
      developed to simulate intrauterine fluid flow pattern and transport phenomena due
      to symmetric and asymmetric wall displacements. The analysis showed that the
      transport phenomena are strongly dependent on the phase shift of wall
      displacement and the angle between the walls. The velocities, flow rates,
      pressure and the axial transport of massless particles are reduced to zero when
      contractions are completely out of phase. Cases of reflux and trapping in a
      tapered channel are discussed for the first time. The reflux phenomenon is most
      likely to occur when wall motility is asymmetric, especially when the angle
      between the walls increases, while trapping is enhanced as the asymmetric
      motility and the angle between the channel walls decrease. The relevance of the
      results to intrauterine fluid transport phenomena, embryo transfer and
      hydrosalpinx was explored.

PMID- 11574255
TI  - Stress analysis of the disc adjacent to interbody fusion in lumbar spine.
AB  - After anterior interbody fusion in the lumbar spine, the accelerated degeneration
      of the disc adjacent to the fusion levels was clinically observed. To understand
      the stress distribution of the adjacent disc, this study created a finite element
      model of the lumbar spine from L1-L5 vertebral body. The fusion model modified
      from the intact model was used to simulate the anterior interbody fusion. Various
      loading conditions, which included flexion, extension, lateral bending, and
      torsion, were applied to the finite element model to study the corresponding
      stress distribution. From the finite element model calculation, at a lower fusion
      site or more fusion levels, the stress of the disc adjacent to interbody fusion
      increased more than upper fusion site or single fusion level under flexion,
      torsion and lateral bending. Larger stress increase was estimated at the upper
      disc adjacent to interbody fusion than the lower disc adjacent to interbody
      fusion. In stress distribution, the upper disc adjacent to interbody fusion had a
      little alteration under torsion.

PMID- 11574256
TI  - The effect of differing Cardan angle sequences on three dimensional lumbo-pelvic
      angular kinematics during running.
AB  - The variability in the three dimensional (3D) lumbo-pelvic angular kinematic
      patterns during running when using differing Cardan angle sequences was
      quantified. Data for four able-bodied subjects running on a treadmill at 4.0 m/s
      were captured using a motion analysis system with six cameras operating at 200
      Hz. The adjusted coefficient of multiple correlation was used to compare
      graphical waveforms whilst the maximum root mean square of the differences was
      used to express the magnitude of any discrepancy in absolute units. Minimal
      qualitative differences were found between the various sequences. Quantitative
      differences between each of the Cardan angle sequences were not found to exceed
      7.0 degrees and 2.8 degrees for the lumbar spine and pelvic rotations
      respectively. It was concluded that different Cardan angle sequences were not
      found to substantially affect typical 3D lumbo-pelvic angular kinematic patterns
      during running.

PMID- 11574257
TI  - Material optimization of femoral component of total hip prosthesis using fiber
      reinforced polymeric composites.
AB  - In this report an integrated approach to the three-dimensional material
      optimization of femoral components of hip prostheses is described. The
      effectiveness of using reinforced fiber composites for the material optimization
      of hip implants has been demonstrated and general guidelines on some material
      design aspects of total hip replacement (THR), in terms of fiber volume fraction
      and fiber orientation angles, are provided. A modular program was developed to
      interface the optimization routine with the finite element code. In this study
      two cases of cemented and non-cemented THR were investigated. In both cases
      perfectly bonded interfaces were assumed. Two objective functions were defined
      based on interface failure criteria and bone adaptive remodeling to avoid
      interface disruption and to reduce the risk of bone loss. The overall results
      demonstrated the effectiveness of the technique, which can provide meaningful
      insights into the fiber-reinforced composite material design of orthopaedic
      implants.

PMID- 11574258
TI  - An investigation of the hammocking effect associated with interface pressure
      measurements using pneumatic tourniquet cuffs.
AB  - A simple experimental arrangement is used to investigate the influence of sensor
      height on the pressure indicated by an inherently linear sensor sandwiched
      between a rigid curved surface and a pneumatic tourniquet cuff. The sensor
      indicated pressure is monitored for sensor heights in the range 0-3 mm and for
      cuff inflation pressures of 0-40 kPa ( approximately 0-300 mmHg). The sensor
      response is found to be non-linear with a saturation tendency at high applied
      pressures. A model which treats the cuff as an elastic membrane draped over the
      sensor is shown to be successful in accounting for the general form of the sensor
      characteristic particularly at cuff pressures greater than about 5 kPa. The model
      is of use in estimating the errors that are likely to arise in intrusive sensors
      used to measure interface pressures under tourniquets.

PMID- 11574259
TI  - Nonpolarized memory T cells.

PMID- 11574260
TI  - New insights into the role of T cells in atopic dermatitis and allergic contact
      dermatitis.

PMID- 11574261
TI  - Annotating genes with potential roles in the immune system: six new members of
      the IL-1 family.

PMID- 11574262
TI  - A new nomenclature for IL-1-family genes.

PMID- 11574263
TI  - The fate of T cells after conditional ablation of TCR.

PMID- 11574264
TI  - Tuning the function of ZAP-70 in vivo.

PMID- 11574275
TI  - Natural anti-HIV antibodies.

PMID- 11574277
TI  - HLA-G remains a mystery.
AB  - In this brief summary, we argue that many widely held beliefs about HLA-G are
      questionable. Recent research has led to a re-evaluation of many of the
      characteristics that were thought to make HLA-G unusual among the MHC class I
      molecules. First, contrary to reports suggesting that the gene encoding HLA-G
      exhibits marked polymorphism in some human populations, recent data have shown
      that the HLA-G gene has comparatively little polymorphism - a feature that might
      allow it to be expressed in the placenta without causing rejection by the
      maternal immune system. Second, although truncated forms of HLA-G are generated
      in the placenta, most of them are unlikely to have significant biological effects
      as they do not reach the cell surface. Third, the hypothesis that a major role of
      HLA-G is to prevent attack of the placenta by maternal natural killer cells is
      now the subject of renewed scrutiny. Finally, there is little evidence that the
      induction of expression of HLA-G is a major mechanism by which tumor cells avoid
      immune attack. HLA-G has once again become as mysterious as when it was
      discovered: an MHC class I molecule expressed at a challengingly extraordinary
      site--the immunologically uneasy interface between mother and fetus.

PMID- 11574278
TI  - HLA-G: a shield against inflammatory aggression.
AB  - Recent developments in the field of HLA-G research have revealed that, besides
      its involvement during pregnancy, HLA-G is expressed in peripheral tissues during
      pathological processes, such as viral infections, malignancies and organ
      transplantation. Here, we discuss recent findings regarding the influence of HLA
      G on the T helper (Th) cytokine balance (favoring Th2-type responses), and the
      expression of HLA-G during chronic, cutaneous inflammatory diseases, such as
      psoriasis and atopic dermatitis. We propose a novel role for HLA-G as a tissue
      protective molecule in inflammatory responses.

PMID- 11574279
TI  - IFN-gamma production by antigen-presenting cells: mechanisms emerge.
AB  - The suggestion that antigen-presenting cells (APCs) produce interferon gamma (IFN
      gamma) is controversial because it conflicts with the initial paradigm in which
      the production of IFN-gamma was restricted to lymphoid cells. However, some
      answers to this skepticism have been provided by recent findings of high-level
      production and intracellular expression of IFN-gamma by interleukin-12 (IL-12)
      stimulated macrophages and dendritic cells. New data are now emerging to explain
      the mechanism of production of IFN-gamma vby APCs. As in lymphoid cells, IL-12
      induced IFN-gamma production in APCs requires signal transducer and activator of
      transcription 4 (STAT4), although the precise molecular events that govern the
      transcription of the gene encoding IFN-gamma are enigmatic still. Understanding
      these processes in lymphoid, and now nonlymphoid, cells remains an important
      challenge.

PMID- 11574280
TI  - The MHC class II transactivator: prey and hunter in infectious diseases.
AB  - The MHC class II transcriptional activator (CIITA) is the major regulator of
      expression of MHC class II genes. Thus, CIITA plays a fundamental role in the
      regulation of the immune response. Here, we discuss our findings on the dual role
      of CIITA during infections, as the target (prey) for certain pathogens but the
      host effector (hunter) against other pathogens, including HIV-1. This dual role
      is placed in an evolutionary context as a rather peculiar example of a strategy
      used by pathogens to evade host defenses and a counteraction of the host to
      minimize the survival and spread of the pathogen.

PMID- 11574281
TI  - Interleukin-7: master regulator of peripheral T-cell homeostasis?
AB  - Recent evidence has implicated interleukin-7 (IL-7) as a master regulator of T
      cell homeostasis, based upon its essential role in the homeostatic expansion of
      naive T-cell populations in response to low-affinity antigens (Ags) and its
      capacity to enhance dramatically the expansion of peripheral T-cell populations
      in response to high-affinity Ags. Furthermore, T-cell-depleted humans have a
      unique inverse relationship between the peripheral CD4(+) T-cell count and the
      level of circulating IL-7. Together, these data suggest that increased amounts of
      IL-7 become available following T-cell depletion, thus, enhancing the high- and
      low-affinity Ag-driven expansion of the population of residual, mature T cells
      and boosting thymic regenerative capacity, as a means to restore T-cell
      homeostasis.

PMID- 11574282
TI  - Gelatinase B: a tuner and amplifier of immune functions.
AB  - Gelatinase B (matrix metalloproteinase-9) is a secreted multidomain enzyme that
      is important for the remodeling of the extracellular matrix and the migration of
      normal and tumor cells. It cleaves denatured collagens (gelatins) and type IV
      collagen, which is present in basement membranes. In the immune system, this
      cleavage helps lymphocytes and other leukocytes to enter and leave the blood and
      lymph circulations. Gelatinase B also cleaves myelin basic protein and type II
      gelatins, and this clipping leads to remnant epitopes that generate autoimmunity,
      the so-called REGA model of autoimmunity. Recently, gelatinase B has been found
      to process cytokines and chemokines, resulting in skewed immune functions.
      Therefore, gelatinase B, often considered as a pure effector molecule, acts as a
      switch and catalyst in both innate and specific immunity, and constitutes a
      prototypic example of the regulation of immune functions by proteolysis.

PMID- 11574285
TI  - Accumulation, distribution and toxicology of dietary nickel in lake whitefish
      (Coregonus clupeaformis) and lake trout (Salvelinus namaycush).
AB  - An 18-day experiment was conducted to investigate the uptake and sublethal
      toxicity of dietary Ni in adult lake whitefish (LWF, Coregonus clupeaformis) and
      lake trout (LT, Salvelinus namaycush) fed diets containing 0, 1000 and 10000
      microg Ni/g, prepared with and without brine shrimp. The results of this
      experiment were used to design an experiment of longer duration in which one of
      the fish species was selected and exposed to lower dietary Ni doses. In the
      present study feed refusal was observed in LT and LWF fed 10000 microg Ni/g,
      after three and 4-5 feedings, respectively. LT fed Ni-contaminated diets
      exhibited different patterns of Ni accumulation than LWF. Increased Ni
      concentrations in all LWF tissues, except the intestine, were associated with
      increased doses of Ni. Copper and Zn concentrations in kidney and liver of LWF
      were altered. Metallothionein concentrations in kidneys of LT fed 1000 microg
      Ni/g and 10000 microg Ni/g and LWF fed 10000 microg Ni/g and in livers of LWF fed
      10000 microg Ni/g (diet without shrimp only) increased significantly. Increased
      lipid peroxide production in the plasma of LT fed 10000 microg Ni/g was observed.
      Blood glucose and electrolytes were affected by Ni exposure. Histopathological
      alterations were observed in kidneys of LWF fed low and high dose diets, livers
      of whitefish fed high dose diets, and intestines of LWF fed high dose diets and
      LT fed low and high dose diets. LT fed high dose diets exhibited significant
      decreases in weight.

PMID- 11574286
TI  - Ethanol- and nicotine-induced membrane changes in embryonic and neonatal chick
      brains.
AB  - In order to study the effects of EtOH and/or nicotine on brain membrane fatty
      acid composition, various concentrations of EtOH and/or nicotine were injected
      into the air sac of chicken eggs at 0 days of incubation. Controls were injected
      with saline. Experimental groups were injected with either 200 micromol EtOH/kg
      egg, 100 micromol nicotine/kg egg, 200 micromol nicotine/kg egg, 200 micromol
      EtOH/kg and 100 micromol nicotine/kg egg, or 200 micromol EtOH/kg and 200
      micromol nicotine/kg egg. In all experimental groups, EtOH- and nicotine-induced
      decreases in brain long-chain polyunsaturated membrane fatty acids were observed
      in stage 44 embryos, stage 45 embryos, and neonatal chicks. These EtOH- and
      nicotine-induced decreases in brain membrane polyunsaturated fatty acids
      correlated with elevated levels of brain lipid hydroperoxides and reduced brain
      acetylcholinesterase (AChE; EC. 3.1.1.7) activities.

PMID- 11574287
TI  - Sialylation is modulated through maturation in hemocytes from Macrobrachium
      rosenbergii.
AB  - In this work we identified in adult and juvenile freshwater prawn, Macrobrachium
      rosenbergii, three major type of circulating hemocytes: fusiform; rounded; and
      large ovoid hemocytes. Rounded and large hemocytes represent the first defense
      line, since this type of cells exerts phagocytic activity as well as lectin
      synthesis. Considering that glycosylation plays important roles in cell
      communication and as a target for pathogenic microorganisms, in this report was
      also described the main glycosidic modifications that occur in the large and
      rounded hemocytes from the freshwater prawn during maturation as determined with
      lectins. Neu5Acalpha2,6Gal, was identified homogeneously distributed in the
      membrane in 90% of hemocytes from juvenile organisms. Maturation of the
      freshwater prawn induced a decrease or complete loss of Neu5Acalpha2,6Gal
      residues that were replaced with Neu5Acalpha2,3 molecules in practically all
      hemocytes from adult organisms. This change was paralleled by a diminution in 9-O
      acetyl-neuraminic acid (Neu5,9Ac(2)) expression. T and Tn antigens (Galbetal,3
      GalNAcalpha1-0-Ser/Thr or GalNAcalpha1-0-Ser/Thr, respectively), as well as N
      glycosidically linked glycans, seem to be highly conserved throughout maturation.
      Our results show that sialylation of freshwater prawn hemocytes is modulated
      throughout the maturation process.

PMID- 11574288
TI  - Thiols and polyamines in the potentiation of malathion toxicity in larval stages
      of the toad Bufo arenarum.
AB  - Treatment with exogenous spermidine enhanced acute malathion toxicity during
      larval development of the toad Bufo arenarum Hensel. The polyamine was rapidly
      incorporated in the larvae with a subsequent metabolization to putrescine and
      spermine, which were excreted to the media. Endogenous polyamine levels were not
      changed by either spermidine or malathion treatments. However, 0.5-mM spermidine
      modified malathion uptake and bioavailability increasing the concentration of the
      xenobiotic in the larvae. The amount of reduced thiols was decreased by both
      compounds, but the depletion was insufficient to induce cytotoxicity. The
      oxidative degradation of polyamines competes for the pool of reduced glutathione
      used in the conjugation of malathion in the larvae, thus leading to the reported
      potentiation of toxicity. Our results suggest that exposure to thiols-depleting
      agents may induce alteration of organophosphate degradation in amphibian larvae.

PMID- 11574289
TI  - Phospholipid alterations elicited by hexachlorobenzene in rat brain are strain
      dependent and porphyria-independent.
AB  - Hexachlorobenzene (HCB) alters phospholipid and heme metabolisms in the liver and
      Harderian gland. The effects of HCB on phospholipid metabolism, in an organ
      considered to be non-responsive to its porphyrinogenic effects, remain to be
      studied. Therefore, as the brain is an organ with this feature, this paper
      analyzes the effects of HCB on brain phospholipid composition in order to
      investigate if there is any relationship between HCB-induced porphyrin metabolism
      disruption and phospholipid alterations. For this purpose, a time-course study of
      HCB effects on brain phospholipids was performed in two strains of rats differing
      in their susceptibility to acquire hepatic porphyria: Chbb THOM (low); and Wistar
      (high). This paper shows for the first time that rat brain phospholipids are
      affected by HCB exposure. Comparative studies show that HCB-induced disturbances
      in brain phospholipid patterns are time and strain-dependent. Thus, whereas major
      phospholipids, phosphatidylcholine and phosphatidylethanolamine were more altered
      in Wistar rats, minor phospholipids, phosphatidylinositol and phosphatidylserine
      were more affected in Chbb THOM rats. HCB intoxication led to a
      sphingomyelin/phosphatidylcholine molar ratio lower than the normal, in both
      strains. As was expected, brain porphyrin content was not altered by HCB
      intoxication in either strain. It can be concluded that HCB is able to alter
      brain phospholipid metabolism in a strain-dependent fashion, and in the absence
      of alterations in brain heme metabolism. In addition, HCB-induced disturbances in
      brain phospholipids were not related to the degree of hepatic porphyria achieved
      by the rats.

PMID- 11574291
TI  - Kupffer cells inhibition prevents hepatic lipid peroxidation and damage induced
      by carbon tetrachloride.
AB  - The aim of this work was to determine if the action mechanism of gadolinium on
      CCl(4)-induced liver damage is by preventing lipid peroxidation (that may be
      induced by Kupffer cells) and its effects on liver carbohydrate metabolism. Four
      groups of rats were treated with CCl(4), CCl(4)+GdCl(3), GdCl(3), and vehicles.
      CCl(4) was given orally (0.4 g 100 g(-1) body wt.) and GdCl(3) (0.20 g 100 g(-1)
      body wt.) was administered i.p. All the animals were killed 24 h after treatment
      with CCl(4) or vehicle. Glycogen and lipid peroxidation were measured in liver.
      Alkaline phosphatase, gamma-glutamyl transpeptidase, alanine amino transferase
      activities and bilirubins were measured in rat serum. A liver histological
      analysis was performed. CCl(4) induced significant elevations on enzyme
      activities and bilirubins; GdCl(3) completely prevented this effect. Liver lipid
      peroxidation increased 2.5-fold by CCl(4) treatment; this effect was also
      prevented by GdCl(3). Glycogen stores were depleted by acute intoxication with
      CCl(4). However, GdCl(3) did not prevent this effect. The present study shows
      that Kupffer cells may be responsible for liver damage induced by carbon
      tetrachloride and that lipid peroxidation is produced or stimulated by Kupffer
      cells, since their inhibition with GdCl(3) prevented both lipid peroxidation and
      CCl(4)-induced liver injury.

PMID- 11574290
TI  - An examination of the potential role of spider digestive proteases as a causative
      factor in spider bite necrosis.
AB  - Tissue necrosis following spider bites is a widespread problem. In the
      continental United States, the brown recluse (Loxosceles reclusa), hobo spider
      (Tegenaria agrestis), garden spider (Argiope aurantia) and Chiracanthium species,
      among others, reportedly cause such lesions. The exact mechanism producing such
      lesions is controversial. There is evidence for both venom sphingomyelinase and
      spider digestive collagenases. We have examined the role of spider digestive
      proteases in spider bite necrosis. The digestive fluid of A. aurantia was assayed
      for its ability to cleave a variety of connective tissue proteins, including
      collagen. Having confirmed that the fluid has collagenases, the digestive fluid
      was injected into the skin of rabbits to observe whether it would cause necrotic
      lesions. It did not. The data do not support the suggestions that spider
      digestive collagenases have a primary role in spider bite necrosis.

PMID- 11574292
TI  - The use of acetylcholinesterase activity in Ruditapes decussatus and Mytilus
      galloprovincialis in the biomonitoring of Bizerta lagoon.
AB  - The variations of acetylcholinesterase activity, considered to be a biochemical
      biomarker of organophosphorus and carbamate compounds, was followed in
      Mediterranean clams (Ruditapes decussatus) and mussels (Mytilus
      galloprovincialis) as a function of season and sampling sites in the lagoon of
      Bizerta (Tunisia). Results show that acetylcholinesterase activity in clams
      collected from station A was the lowest and was so throughout the year. This low
      activity may be due to the input of non-treated waste waters in the lagoon. Heavy
      metal contamination has been reported in the sediments of this area, suggesting
      that acetylcholinesterase activity in clams may be inhibited by this type of
      pollution. Clams harvested from station F, a site adjacent to an agricultural
      area, were characterized by a decrease in acetylcholinesterase activity,
      especially after rain periods. Clams from station J presented the highest
      activity throughout the greater part of the year. This phenomenon may imply that
      this location is less affected by pollutants inhibiting AChE activity than the
      others. In the mussels from station C, located in the channel from the lagoon to
      the Mediterranean and submitted to pollutants (urban wastes from Bizerta and
      hydrocarbons from the maritime traffic), acetylcholinesterase activities were
      lower than in those from station J. In conclusion, the variations in
      acetylcholinesterase activity observed between stations in both species may be
      the result of pollution and of the environmental conditions.

PMID- 11574293
TI  - Tannins--a dietary problem for hand-reared grey partridge Perdix perdix after
      release?
AB  - A 4-week feeding trial on 22 grey partridges Perdix perdix was conducted in this
      study. Seven birds were fed commercial poultry food, seven natural food and eight
      commercial poultry food containing 6% of quebracho-tannin. Our results suggest
      that 6% dietary tannin, when added to a commercial food with high protein
      content, effects the grey partridge only slightly. No difference was seen in food
      consumption and body mass remained stable. However, birds fed tannin had longer
      small intestines, which most probably indicate gastrointestinal detoxication.
      They also excreted a high amount of tannin in their faeces. In addition, no
      between-group variation was seen in cytochrome P450 enzymes. Birds fed natural
      food had high concentration of nitrogen in intestinal excreta and high plasma
      alanine concentrations. They also suffered a rapid decrease in body mass after
      the change in diet and their body mass remained low. This may indicate increased
      protein excretion and/or catabolism of endogenous nutrient reserves. Potential
      short-term effects of the change in diet were seen in plasma. These findings
      coincide with the high mortality period of birds released into the wild.

PMID- 11574294
TI  - Stimulatory effects of selected PAHs on testosterone production in goldfish and
      rainbow trout and possible mechanisms of action.
AB  - This study investigates the effects of selected polycyclic aromatic hydrocarbons
      (PAHs) on testicular function in fish. In vitro incubations of goldfish testis
      tissue exposed to three selected PAHs [naphthalene, beta-naphthoflavone (betaNF),
      or retene] resulted in biphasic potentiation of gonadotropin (GtH)-stimulated
      testosterone (T) production, with no effect on basal levels. In vivo exposure of
      goldfish to betaNF also resulted in biphasic increases in plasma T levels.
      Experiments with rainbow trout revealed increased levels of in vitro T production
      when exposed to naphthalene, albeit only at higher concentrations than the
      responses observed in goldfish. Studies of possible sites of action at the level
      of the goldfish testis showed that betaNF exerted its most potent action when T
      production was initiated by a ligand such as GtH or prostaglandin E(2). Within
      the steroidogenic pathway, betaNF potentiation of GtH-stimulated T production may
      be partially mediated by increases in cAMP production, but appear to be
      independent of cytosolic calcium content. These studies demonstrate that PAHs may
      function as disruptors of reproductive endocrine function in teleosts through the
      unexpected effect of enhancing testicular steroidogenesis.

PMID- 11574295
TI  - Profiles of growth hormone and insulin secretion, and glucose response to insulin
      in growing Japanese Black heifers (beef type): comparison with Holstein heifers
      (dairy type).
AB  - Nine Japanese Black and 10 Holstein heifers ranging from 1 week (wk) to 18 months
      (mo) old received a single bolus intravenous injection of GH-releasing factor
      (GRF, 0.25-microg/kg BW), glucose (112.5-mg/kg BW) or insulin (0.2-U/kg BW) at
      various stages through 18 mo of age. The GH secretory response to exogenous GRF
      in Japanese Black heifers was lower than that in Holstein heifers at all stages
      of growth. While insulin secretory function was not very different in both breeds
      from 1 to 12 mo of age, the insulin response was much higher in Japanese Black
      heifers than in Holstein heifers after sexual maturation. The degree of decrease
      in plasma glucose following insulin injection was similar in both breeds at each
      stage of growth. It is concluded that compared with Holstein heifers, Japanese
      Black heifers have lower GH and higher insulin secretory functions, and that the
      two breeds have similar glucose response to insulin.

PMID- 11574297
TI  - Health status of the Pakistani population.

PMID- 11574298
TI  - Treatment of tuberculosis in Haiti.

PMID- 11574301
TI  - The CARE-CDC health initiative: a model for global participatory research.

PMID- 11574302
TI  - Melding disparate cultures and capacities to create global health partnerships.

PMID- 11574303
TI  - Making health a priority of US foreign policy.

PMID- 11574304
TI  - US public health leaders shift toward a new paradigm of global health.

PMID- 11574305
TI  - Using folk media in HIV/AIDS prevention in rural Ghana.
AB  - The pandemic of HIV/AIDS continues to pose a serious threat to the population of
      sub-Saharan Africa, despite ongoing public health efforts to control the spread
      of infection. Given the important role of oral tradition in indigenous settings
      throughout rural Africa, we are beginning an innovative approach to HIV/AIDS
      prevention based on the use of folk media. This commentary explains the types of
      folk media used in the traditional Ghanaian setting and explores their
      consistency with well-known theories. Folk media will be integrated with
      broadcast radio for interventions under the HIV/AIDS Behavior Change
      Communication Project being undertaken as part of the CARE-CDC Health Initiative
      (CCHI) in 2 districts in Ghana.

PMID- 11574306
TI  - Managing newborn health in the global community.
AB  - The largest health disparities in the world are found in maternal and neonatal
      mortality figures between the industrialized countries and the poorest sections
      of the poorest countries. Young lives would be saved if the skills and knowledge
      that have been accumulated by health workers around the world could be readily
      applied. The problems reside with lack of management resources rather than lack
      of scientific knowledge. "The Healthy Newborn: A Reference Manual for Program
      Managers" is a graduate course in management aimed at providing health to
      newborns and healthy newborns to communities.

PMID- 11574307
TI  - Not just a drop in the bucket: expanding access to point-of-use water treatment
      systems.
AB  - Since 1990, the number of people without access to safe water sources has
      remained constant at approximately 1.1 billion, of whom approximately 2.2 million
      die of waterborne disease each year. In developing countries, population growth
      and migrations strain existing water and sanitary infrastructure and complicate
      planning and construction of new infrastructure. Providing safe water for all is
      a long-term goal; however, relying only on time- and resource-intensive
      centralized solutions such as piped, treated water will leave hundreds of
      millions of people without safe water far into the future. Self-sustaining,
      decentralized approaches to making drinking water safe, including point-of-use
      chemical and solar disinfection, safe water storage, and behavioral change, have
      been widely field-tested. These options target the most affected, enhance health,
      contribute to development and productivity, and merit far greater priority for
      rapid implementation.

PMID- 11574308
TI  - Challenges in implementing a point-of-use water quality intervention in rural
      Kenya.
AB  - To prevent diarrheal diseases in western Kenya, CARE Kenya initiated the Water,
      Sanitation, and Education for Health (WASEH) Project in 1998. The project targets
      72 farming and fishing communities with a total population of 43 000. Although
      the WASEH Project facilitated construction of shallow wells and pit latrines, the
      water quality still needed improvement. Consequently, in 2001, CARE implemented
      the Safe Water System (which consists of point-of-use water treatment with sodium
      hypochlorite, safe storage, and behavior change techniques) within the already
      established WASEH infrastructure, using existing community organizations in
      combination with a social marketing approach that introduced affordable products.
      The project has resulted in adoption rates of 33.5% for chemical water treatment
      and 18.5% for clay pots modified for safe water storage.

PMID- 11574309
TI  - Collaboration, cholera, and cyclones: a project to improve point-of-use water
      quality in Madagascar.
AB  - In November 1999, CARE Madagascar, Population Services International (PSI), and
      the Centers for Disease Control and Prevention (CDC) selected 30 poor communities
      in urban Antananarivo as the target population for launch of the Safe Water
      System. The system consists of behavior change techniques along with point-of-use
      treatment and safe storage of water. The project was launched in March 2000,
      ahead of schedule, because a cholera epidemic struck Madagascar in January.
      Because of the enormous demand created by the cholera epidemic and by 3 cyclones
      that followed in the next 3 months, the project grew to national scale in less
      than a year. The combination of community mobilization and social marketing
      resulted in increased demand for and use of the Safe Water System.

PMID- 11574310
TI  - Impact of the safe water system on water quality in cyclone-affected communities
      in Madagascar.
AB  - Cyclone Hudah struck the northeastern coast of Madagascar in the spring of 2000.
      Over a 5-month period, 11 700 relief kits consisting of bottles of water
      disinfectant and foldable jerry cans were distributed to the affected population.
      Five months after the cyclone, a survey was conducted in 12 villages to determine
      the impact of these relief kits on water quality. Seventy-six percent of the
      surveyed households reported using jerry cans, and 65% reported using the
      disinfectant. Stored water in households using both products had significantly
      less microbiological contamination than stored water in other households. To
      improve the prospects for a sustainable intervention, the response plan for
      future disasters should incorporate a transition to recovery and development,
      including formative research into local customs, beliefs, and water handling
      habits, and funding support to initiate social marketing.

PMID- 11574311
TI  - Community environmental health assessment in Peru's desert hills and rainforest.
AB  - Peru's expanding population and rapid urbanization--a result of migration to its
      largest cities--have stressed the country's public services infrastructure and
      the provision of public health and environmental health services. In response,
      the Ministry of Health established the General Directorate of Environmental
      Health (DIGESA), the branch charged with assuring adequate environmental health
      services to populations in rural and urban areas. The magnitude of the
      environmental health problems in peri-urban settlements, however, has exceeded
      the capacity of DIGESA to respond. The Urban Environmental Health Project is an
      effort to develop the ability of local communities to address these problems

PMID- 11574312
TI  - Trapping the vector: community action to curb sleeping sickness in southern
      Sudan.
AB  - South Sudan experienced a resurgence of trypanosomiasis (sleeping sickness) in
      the 1990s. In 1997 in Tambura County, public health officials combined standard
      mass screening and treatment techniques for infected persons with an additional
      component-trapping the vectors of the disease. The intent of this integrated
      approach was to lower the number and concentration of the tsetse flies that
      spread the disease while reducing the level of infection in the human population
      to make the likelihood of transmission extremely low. Because the trapping
      project depends on village participation (making, setting, and maintaining the
      traps), village volunteers and their neighbors learned more about the causes and
      prevention of sleeping sickness and became much more willing to participate in
      serosurveys and to seek treatment.

PMID- 11574313
TI  - Developing public health management training capacity in Nicaragua.
AB  - The Cooperative for Assistance and Relief Everywhere (CARE) and Centers for
      Disease Control and Prevention (CDC) Health Initiative in Nicaragua is
      distinctive in its focus on developing a cadre of in-country trainers whose aim
      is to equip frontline public health managers with widely applicable tools and
      techniques to assist them in identifying and solving implementation problems.
      Since 1999, 137 trainees--37% more than originally planned--have demonstrated
      competence by completing and presenting applied management projects. Nineteen
      professors from the preventive medicine faculty at the Autonomous University of
      Nicaragua also have been trained. The country office now has a cadre of seasoned
      trainers who can meet the ongoing management training needs of CARE staff and
      their counterparts in the Ministry of Health and in other nongovernmental
      organizations.

PMID- 11574314
TI  - Transportation for maternal emergencies in Tanzania: empowering communities
      through participatory problem solving.
AB  - Inadequate health care and long delays in obtaining care during obstetric
      emergencies are major contributors to high maternal death rates in Tanzania.
      Formative research conducted in the Mwanza region identified several
      transportation-related reasons for delays in receiving assistance. In 1996, the
      Cooperative for Assistance and Relief Everywhere (CARE) and the Centers for
      Disease Control and Prevention (CDC) began an effort to build community capacity
      for problem-solving through participatory development of community-based plans
      for emergency transportation in 50 villages. An April 2001 assessment showed that
      19 villages had begun collecting funds for transportation systems; of 13 villages
      with systems available, 10 had used the system within the last 3 months.
      Increased support for village health workers and greater participation of women
      in decision making were also observed.

PMID- 11574315
TI  - Saudi nutrition education for pregnant women, 1988.

PMID- 11574316
TI  - Social medicine then and now: lessons from Latin America.
AB  - The accomplishments of Latin American social medicine remain little known in the
      English-speaking world. In Latin America, social medicine differs from public
      health in its definitions of populations and social institutions, its dialectic
      vision of "health-illness," and its stance on causal inference. A "golden age"
      occurred during the 1930s, when Salvador Allende, a pathologist and future
      president of Chile, played a key role. Later influences included the Cuban
      revolution, the failed peaceful transition to socialism in Chile, the Nicaraguan
      revolution, liberation theology, and empowerment strategies in education. Most of
      the leaders of Latin American social medicine have experienced political
      repression, partly because they have tried to combine theory and political
      practice--a combination known as "praxis." Theoretic debates in social medicine
      take their bearings from historical materialism and recent trends in European
      philosophy. Methodologically, differing historical, quantitative, and qualitative
      approaches aim to avoid perceived problems of positivism and reductionism in
      traditional public health and clinical methods. Key themes emphasize the effects
      of broad social policies on health and health care; the social determinants of
      illness and death; the relationships between work, reproduction, and the
      environment; and the impact of violence and trauma.

PMID- 11574317
TI  - Modeling and reinforcement to combat HIV: the MARCH approach to behavior change.
AB  - Theory and research suggest that behavioral interventions to prevent HIV/AIDS may
      be most effective when they are personalized and affectively compelling, when
      they provide models of desired behaviors, and when they are linked to social and
      cultural narratives. Effective strategies must also take into account the
      opportunities and obstacles present in the local environment. The Modeling and
      Reinforcement to Combat HIV (MARCH) projects combine key aspects of individual
      behavior change with efforts to change social norms. There are 2 main components
      to the program: entertainment as a vehicle for education (longrunning serialized
      dramas on radio or television portray role models evolving toward the adoption of
      positive behaviors) and interpersonal reinforcement at the community level
      (support from friends, family members, and others can help people initiate
      behavior changes; support through changes in social norms is necessary for
      behavioral effects to be sustained over time). Both media and interpersonal
      intervention activities should be linked to existing resources in the community
      and, wherever possible, provide increased access to preventive services,
      supplies, and other supporting elements.

PMID- 11574318
TI  - Cholera prevention with traditional and novel water treatment methods: an
      outbreak investigation in Fort-Dauphin, Madagascar.

PMID- 11574319
TI  - Seeking safe storage: a comparison of drinking water quality in clay and plastic
      vessels.

PMID- 11574321
TI  - Monitoring behavioral risk factors for cardiovascular disease in Russia.

PMID- 11574320
TI  - Care seeking during fatal childhood illnesses: Siaya District, Kenya, 1998.

PMID- 11574323
TI  - Mortality from unintentional injuries in Japan, 1899-1998.

PMID- 11574322
TI  - Hormonal pregnancy tests in sub-Saharan Africa.

PMID- 11574324
TI  - Community health worker performance in the management of multiple childhood
      illnesses: Siaya District, Kenya, 1997-2001.
AB  - OBJECTIVES: To characterize community health worker (CHW) performance using an
      algorithm for managing common childhood illnesses in Siaya District, Kenya, we
      conducted CHW evaluations in 1998, 1999, and 2001. METHODS: Randomly selected
      CHWs were observed managing sick outpatient and inpatient children at a hospital,
      and their management was compared with that of an expert clinician who used the
      algorithm. RESULTS: One hundred, 108, and 114 CHWs participated in the
      evaluations in 1998, 1999, and 2001, respectively. The proportions of children
      treated "adequately" (with an antibiotic, antimalarial, oral rehydration
      solution, or referral, depending on the child's disease classifications) were
      57.8%, 35.5%, and 38.9%, respectively, for children with a severe classification
      and 27.7%, 77.3%, and 74.3%, respectively, for children with a moderate (but not
      severe) classification. CHWs adequately treated 90.5% of malaria cases (the most
      commonly encountered classification). CHWs often made mistakes assessing
      symptoms, classifying illnesses, and prescribing correct doses of medications.
      CONCLUSIONS: Deficiencies were found in the management of sick children by CHWs,
      although care was not consistently poor. Key reasons for the deficiencies appear
      to be guideline complexity and inadequate clinical supervision; other possible
      causes are discussed.

PMID- 11574325
TI  - Management of childhood illness at health facilities in Benin: problems and their
      causes.
AB  - OBJECTIVES: To prepare for the implementation of Integrated Management of
      Childhood Illness (IMCI) in Benin, we studied the management of ill children
      younger than 5 years at outpatient health facilities. METHODS: We observed a
      representative sample of consultations; after each consultation, we interviewed
      caregivers and reexamined children. Health workers' performance was evaluated
      against IMCI guidelines. To identify determinants of performance, statistical
      modeling was performed and 6 focus groups with health workers were conducted to
      solicit their opinions. RESULTS: Altogether, 584 children were enrolled and 101
      health workers were observed; 130 health workers participated in focus group
      discussions. Many serious deficiencies were found: incomplete assessment of
      children's signs and symptoms, incorrect diagnosis and treatment of potentially
      life-threatening illnesses, inappropriate prescription of dangerous sedatives,
      missed opportunities to vaccinate, and failure to refer severely ill children for
      hospitalization. Quantitative and qualitative analyses showed various health
      facility-, health worker-, caregiver-, and child-related factors as possible
      determinants of health worker performance. CONCLUSIONS: Action is urgently
      needed. Our results suggest that to improve health care delivery, interventions
      should target both the health system and the community level.

PMID- 11574326
TI  - Improving surveillance for maternal and perinatal health in 2 districts of rural
      Tanzania.
AB  - OBJECTIVES: As part of a community-based reproductive health project in rural
      Tanzania, a maternal and perinatal health care surveillance system was
      established to monitor pregnancy outcomes. This report presents preliminary
      results. METHODS: Village health workers were trained to collect data during
      health education visits to pregnant and postpartum women. Maternal and fetal or
      infant survival or deaths were tracked on a community monitoring board. RESULTS:
      Among 904 pregnancies, the fetoneonatal mortality rate was 69.4 deaths per 1000
      live births and fetal deaths; 4 maternal deaths occurred. Intrapartum and early
      neonatal deaths of infants with birthweights of 1500 g or greater represented a
      large proportion of deaths. CONCLUSIONS: These preliminary results will be used
      to prioritize project interventions, including increasing access to skilled
      delivery care.

PMID- 11574327
TI  - Obesity and undernutrition and cardiovascular risk factors in rural and urban
      Gambian communities.
AB  - OBJECTIVES: This study documented the prevalence of and cardiovascular risk
      factors associated with obesity and undernutrition in the Gambia. METHODS: Adults
      (> or =15 years; N = 5373) from rural and urban areas completed a questionnaire;
      their height, weight, and waist and hip circumferences were measured, and their
      cardiovascular risk factors were assessed. RESULTS: Prevalence of undernutrition
      (body mass index < 18 kg/m(2)) was 18.0%; all strata of society were affected.
      Prevalence of obesity (body mass index > or =30 kg/m(2)) was 4.0% but was higher
      (32.6%) among urban women 35 years or older. Cardiovascular risk factors were
      more prevalent among obese participants. CONCLUSIONS: Undernutrition coexists
      with obesity, demonstrating a "double burden of disease." Differential
      interventions should focus on high-risk groups; prevention needs a multisectorial
      approach.

PMID- 11574328
TI  - Growth in indigenous and nonindigenous Chilean schoolchildren from 3 poverty
      strata.
AB  - OBJECTIVES: This study sought to determine whether the short stature of Mapuche
      children, an indigenous group in Chile, reflects poverty or genetic heritage and
      whether the international reference population, derived from studies of US
      children of mostly European origin, is appropriate for assessing growth failure
      in indigenous peoples of the Americas. METHODS: The study assessed 768
      schoolchildren of Mapuche and non-Mapuche ancestry, aged 6 to 9 years, living
      under conditions of extreme, medium, and low poverty. RESULTS: Growth retardation
      was strongly related to poverty in both ethnic groups. Within poverty levels,
      there were no significant differences in stature between ethnic groups, and in
      low-poverty areas in Santiago, the capital city, mean stature was only slightly
      less than in the reference population. CONCLUSIONS: Poverty, not ancestry,
      explains the short stature of Mapuche children, and use of the international
      reference to assess growth in this population is appropriate.

PMID- 11574329
TI  - Extrarelational sex among Mexican men and their partners' risk of HIV and other
      sexually transmitted diseases.
AB  - OBJECTIVES: This study explored the risk of HIV and other sexually transmitted
      diseases (STDs) among married and cohabiting women in Mexico City, Mexico,
      derived from their partners' sexual behaviors. METHODS: Results were derived from
      the first population-based household survey in Mexico that investigated male
      sexual behavior. Analyses were restricted to sexually active married or
      cohabiting men (n = 3990). RESULTS: Fifteen percent of the men reported
      extrarelational sex during the past year, 9% reported condom use during last
      intercourse, and 80% perceived no HIV risk. Most secondary partners were
      coworkers, mistresses, or friends. CONCLUSIONS: Targeted HIV and STD prevention
      efforts appear necessary because a substantial number of women may be at risk.

PMID- 11574330
TI  - Smoking among youths in China.
AB  - OBJECTIVES: To inform a prevention strategy, this study determined the prevalence
      of and attitudes toward smoking among Chinese secondary school students. METHODS:
      Self-completion questionnaires were administered to 13- to 18-year-olds attending
      school in Zhejiang Province, eastern China. RESULTS: Of the 6674 respondents,
      15.9% (25.7% of the boys, 5.4% of the girls) were ever smokers. Only 0.3% were
      regular smokers. Of the ever smokers, 41.9% had smoked before 10 years of age and
      7.9% before 5 years of age. Parental smoking was the strongest predictor of
      smoking. CONCLUSIONS: The very low prevalence of regular smoking found in this
      age group suggests that prevention programs in school may be beneficial. Parents
      should be encouraged to adopt more responsible attitudes toward smoking in the
      home.

PMID- 11574331
TI  - Results of the expanded program on immunization in the Macedonian refugee camps.
AB  - OBJECTIVES: This report summarizes the results of the Macedonian refugee camps'
      Expanded Program on Immunization. METHODS: Government agencies and
      nongovernmental organizations implemented an immunization program consisting of 3
      mass vaccination campaigns in each of the 7 camps. Before the second mass
      campaign, weekly immunization clinics were initiated in each camp. Children
      younger than 48 months were immunized against 8 antigens according to a schedule
      established by the Macedonian Ministry of Health. RESULTS: Immunization coverage
      rates in the second campaign were 91% in Cegrane and 73% in Brazda. Coverage
      rates of the weekly clinics averaged 93%. CONCLUSIONS: Initiating an expanded
      immunization program in the absence of a stable population is problematic.

PMID- 11574332
TI  - Self-assessed health among indigenous Australians: how valid is a global
      question?
AB  - OBJECTIVES: This study assessed the validity of a global measure of self-assessed
      health among Indigenous Australians. METHODS: Logistic regression was used to
      identify factors associated with self-assessed health in a nationally
      representative sample. RESULTS: Among 8782 adult respondents, poorer self
      assessed health was strongly associated with several factors, including age,
      number of health conditions, and recent health actions. The association with
      health conditions was attenuated when the respondent's primary language was not
      English. CONCLUSIONS: Self-assessed health may be a valid measure among
      indigenous Australians whose primary language is English. However, although the
      measure draws on common experiences of health and illness, it may obscure
      differences in how people incorporate these experiences into social actions.

PMID- 11574333
TI  - Factors linked to bacterial vaginosis in nonpregnant women.
AB  - OBJECTIVES: The purposes of this study were to test the hypothesis that vaginal
      douching is linked to bacterial vaginosis in both symptomatic and asymptomatic
      women and to identify other demographic, reproductive, and lifestyle factors
      associated with bacterial vaginosis. METHODS: In this cross-sectional study
      involving 3 clinic sites, 496 nonpregnant women completed a self-administered
      questionnaire. Their vaginal smears were assessed and cross-validated for
      bacterial vaginosis. RESULTS: The prevalence of bacterial vaginosis across
      clinics ranged from 15% to 30%. In analyses restricted to site 1, adjusted odds
      ratios (ORs) for bacterial vaginosis remained significant for African American
      women with 13 or fewer years of education (OR = 5.5, 95% confidence interval [CI]
      = 2.1, 14.5), hormone use within the past 6 months (OR = 0.5, 95% CI = 0.2, 0.8),
      and vaginal douching within the past 2 months (OR = 2.9, 95% CI = 1.5, 5.6).
      CONCLUSIONS: Two lifestyle factors emerge as strongly associated with bacterial
      vaginosis: systemic contraceptives appear protective, whereas douching is linked
      to an increase in prevalence. The temporal relationship between douching and
      bacterial vaginosis needs further clarification.

PMID- 11574334
TI  - Predictors of low back pain onset in a prospective British study.
AB  - OBJECTIVES: This study examined predictors of low back pain onset in a British
      birth cohort. METHODS: Univariate and multivariate analyses focused on
      individuals who experienced onset of low back pain at 32 to 33 years of age (n=
      571) and individuals who were pain free (n = 5210). Participants were members of
      the 1958 British birth cohort. RESULTS: Incident pain was elevated among those
      with psychological distress at 23 years of age (adjusted odds ratio [OR] = 2.52,
      95% confidence interval [CI] = 1.65, 3.86) and among persistent moderate or heavy
      smokers (adjusted OR = 1.63, 95% CI = 1.23, 2.17). Significant univariate
      associations involving other factors (e.g., social class, childhood emotional
      status, body mass index, job satisfaction) did not persist in multivariate
      analyses. CONCLUSIONS: This prospectively studied cohort provides evidence that
      psychological distress more than doubles later risk of low back pain, with
      smoking having a modest independent effect. Other prospective studies are needed
      to confirm these findings before implications for low back pain prevention can be
      assessed.

PMID- 11574335
TI  - Partner violence among adolescents in opposite-sex romantic relationships:
      findings from the National Longitudinal Study of Adolescent Health.
AB  - OBJECTIVES: This report examines (1) the prevalence of psychological and minor
      physical violence victimization in a nationally representative sample of
      adolescents and (2) associations between sociodemographic factors and
      victimization. METHODS: Analyses are based on 7500 adolescents who reported
      exclusively heterosexual romantic relationships in the National Longitudinal
      Study of Adolescent Health. Items from the Conflict Tactics Scale were used to
      measure victimization. Associations between victimization patterns and
      sociodemographic characteristics were assessed with polytomous logistic
      regression. RESULTS: One third of adolescents reported some type of
      victimization, and 12% reported physical violence victimization. Although most
      sociodemographic characteristics were significantly associated with
      victimization, patterns varied by sex and type of victimization. CONCLUSIONS:
      Psychological and minor physical violence victimization is common in opposite-sex
      romantic relationships during adolescence. The sex-specific associations between
      sociodemographic characteristics and patterns of partner violence victimization
      underscore the importance of pursuing longitudinal, theory-driven investigations
      of the characteristics and developmental histories of both partners in a couple
      to advance understanding of this public health problem.

PMID- 11574336
TI  - A motivational interviewing intervention to increase fruit and vegetable intake
      through Black churches: results of the Eat for Life trial.
AB  - OBJECTIVES: This study reports on Eat for Life, a multicomponent intervention to
      increase fruit and vegetable consumption among African Americans that was
      delivered through Black churches. METHODS: Fourteen churches were randomly
      assigned to 3 treatment conditions: (1) comparison, (2) self-help intervention
      with 1 telephone cue call, and (3) self-help with 1 cue call and 3 counseling
      calls. The telephone counseling in group 3 was based on motivational
      interviewing. The primary outcome, assessed at baseline and 1-year follow-up, was
      fruit and vegetable intake as assessed by 3 food frequency questionnaires.
      RESULTS: Change in fruit and vegetable intake was significantly greater in the
      motivational interviewing group than in the comparison and self-help groups. The
      net difference between the motivational interviewing and comparison groups was
      1.38, 1.03, and 1.21 servings of fruits and vegetables per day for the 2-item, 7
      item, and 36-item food frequency questionnaires, respectively. The net difference
      between the motivational interviewing and self-help groups was 1.14, 1.10, and
      0.97 servings for the 2-item, 7-item, and 36-item food frequency questionnaires,
      respectively. CONCLUSIONS: Motivational interviewing appears to be a promising
      strategy for modifying dietary behavior, and Black churches are an excellent
      setting to implement and evaluate health promotion programs.

PMID- 11574337
TI  - Lactate versus chloride: which is better?

PMID- 11574338
TI  - The effects of balanced versus saline-based hetastarch and crystalloid solutions
      on acid-base and electrolyte status and gastric mucosal perfusion in elderly
      surgical patients.
AB  - The IV administration of sodium chloride solutions may produce a metabolic
      acidosis and gastrointestinal dysfunction. We designed this trial to determine
      whether, in elderly surgical patients, crystalloid and colloid solutions with a
      more physiologically balanced electrolyte formulation, such as Hartmann's
      solution and Hextend, can provide a superior metabolic environment and improved
      indices of organ perfusion when compared with saline-based fluids. Forty-seven
      elderly patients undergoing major surgery were randomly allocated to one of two
      study groups. Patients in the Balanced Fluid group received an intraoperative
      fluid regimen that consisted of Hartmann's solution and 6% hetastarch in balanced
      electrolyte and glucose injection (Hextend). Patients in the Saline group were
      given 0.9% sodium chloride solution and 6% hetastarch in 0.9% sodium chloride
      solution (Hespan). Biochemical indices and acid-base balance were determined.
      Gastric tonometry was used as a reflection of splanchnic perfusion. Postoperative
      chloride levels demonstrated a larger increase in the Saline group than the
      Balanced Fluid group (9.8 vs 3.3 mmol/L, P = 0.0001). Postoperative standard base
      excess showed a larger decline in the Saline group than the Balanced Fluid group
      (-5.5 vs -0.9 mmol/L, P = 0.0001). Two-thirds of patients in the Saline group,
      but none in the Balanced Fluid group, developed postoperative hyperchloremic
      metabolic acidosis (P = 0.0001). Gastric tonometry indicated a larger increase in
      the CO2 gap during surgery in the Saline group compared with the Balanced Fluid
      group (1.7 vs 0.9 kPa, P = 0.0394). In this study, the use of balanced
      crystalloid and colloid solutions in elderly surgical patients prevented the
      development of hyperchloremic metabolic acidosis and resulted in improved gastric
      mucosal perfusion when compared with saline-based solutions. IMPLICATIONS: This
      prospective, randomized, blinded trial showed that, in elderly surgical patients,
      the use of balanced IV solutions can prevent the development of hyperchloremic
      metabolic acidosis and provide better gastric mucosal perfusion compared with
      saline-based fluids.

PMID- 11574339
TI  - Normal saline versus lactated Ringer's solution for intraoperative fluid
      management in patients undergoing abdominal aortic aneurysm repair: an outcome
      study.
AB  - Metabolic acidosis and changes in serum osmolarity are consequences of 0.9%
      normal saline (NS) solution administration. We sought to determine if these
      physiologic changes influence patient outcome. Patients undergoing aortic
      reconstructive surgery were enrolled and were randomly assigned to receive
      lactated Ringer's (LR) solution (n = 33) or NS (n = 33) in a double-blinded
      fashion. Anesthetic and fluid management were standardized. Multiple measures of
      outcome were monitored. The NS patients developed a hyperchloremic acidosis and
      received more bicarbonate therapy (30 +/- 62 mL in the NS group versus 4 +/- 16
      mL in the LR group; mean +/- SD), which was given if the base deficit was greater
      than -5 mEq/L. The NS patients also received a larger volume of platelet
      transfusion (478 +/- 302 mL in the NS group versus 223 +/- 24 mL in the LR group;
      mean +/- SD). When all blood products were summed, the NS group received
      significantly more blood products (P = 0.02). There were no differences in
      duration of mechanical ventilation, intensive care unit stay, hospital stay, and
      incidence of complications. When NS was used as the primary intraoperative
      solution, significantly more acidosis was seen on completion of surgery. This
      acidosis resulted in no apparent change in outcome but required larger amounts of
      bicarbonate to achieve predetermined measurements of base deficit and was
      associated with the use of larger amounts of blood products. These changes should
      be considered when choosing fluids for surgical procedures involving extensive
      blood loss and requiring extensive fluid administration. IMPLICATIONS:
      Predominant use of 0.9% saline solution in major surgery has little impact on
      outcome as assessed by duration of mechanical ventilation, intensive care unit
      stay, hospital stay, and postoperative complications, but it does appear to be
      associated with increased perioperative blood loss.

PMID- 11574341
TI  - The dynamics of vascular volume and fluid shifts of lactated Ringer's solution
      and hypertonic-saline-dextran solutions infused in normovolemic sheep.
AB  - Infusions of hyperosmotic-hyperoncotic solutions such as hypertonic saline
      dextran (HSD) are used in Europe for resuscitation of traumatic shock and
      perioperative volume support as an adjunct to conventional isotonic crystalloids.
      Whereas plasma volume expansion of HSD has been measured at single time points
      after the intravascular volume expansion, the detailed time course of fluid
      shifts during and after infusions have not been reported. We compared the time
      course of volume expansion during and after 30-min infusions of 4 mL/kg HSD and
      25 mL/kg lactated Ringer's solution (LR) in normovolemic conscious splenectomized
      sheep. Peak plasma volume (Evans blue and hemoglobin dilution) expansion was
      similar for HSD (7.8 +/- 0.9 mL/kg) and the larger sixfold volume of LR (7.2 +/-
      0.5 mL/kg). However, 30 min after the 30-min infusion (T60), plasma expansion
      remained larger after HSD (5.1 +/- 0.9 mL/kg) than after LR (1.7 +/- 0.6 mL/kg).
      Both solutions caused an equivalent diuresis. Intravascular volume expansion
      efficiency (VEE), defined as milliliter plasma expansion/milliliter fluid infused
      at 0 (T30), 30 (T60), and 60 (T90) min after infusion ended was 1.8, 1.3, and
      0.8, respectively for HSD, whereas LR provided a VEE of only 0.27, 0.07, and
      0.07. The relative expansion efficiency of HSD versus LR, calculated as the ratio
      (VEE(HSD)/VEE(LR)), was 7-fold that of LR at the end of infusion T30, and 20-fold
      at T60, but decreased to 9-fold by T120. Intravascular volume dynamic studies of
      different volume expanders in animals and patients may provide anesthesiologists
      with a new tool for monitoring the effectiveness of fluid therapy. IMPLICATIONS:
      Hypertonic saline dextran (HSD) is a new plasma expander recently approved for
      clinical use in Europe. We compared the plasma volume expansion of HSD versus
      lactated Ringers (LR) in normovolemic sheep. After a 30 min infusion, HSD was 7
      times as effective at expanding volume as an equal volume of LR, but for the next
      90 minutes the relative effectiveness of HSD increased to 10-20 times.

PMID- 11574342
TI  - The effects of hemoglobin glutamer-200 (bovine) on the microcirculation in a
      canine hypovolemia model: a noninvasive computer-assisted intravital microscopy
      study.
AB  - We sought to correlate in vivo microvascular, systemic function, hemodynamic, and
      oxygenation changes in autologous shed blood (n = 4) and hemoglobin glutamer-200
      (Hb-200) (n = 4) resuscitations in hypovolemic dogs. Hemorrhage (approximately
      40% blood loss) reduced mean arterial pressure to approximately 50 mm Hg and
      caused significant (P < 0.01) decreases in hematocrit, total hemoglobin, mean
      pulmonary arterial pressure, cardiac output, and oxygen delivery and significant
      (P < 0.01) increases in heart rate, systemic vascular resistance, and lactic
      acidosis. Significant (P < 0.01) changes in conjunctival microvascular variables
      also occurred, including a 19% decrease in venular diameter and 79% increase in
      average blood flow velocity. Shed blood resuscitation returned microvascular,
      systemic function, hemodynamic, and oxygenation variables to prehemorrhagic
      baseline values. In contrast, Hb-200 failed to restore hematocrit, total
      hemoglobin, cardiac output, oxygen delivery index, and systemic venous resistance
      to baseline, but it restored other systemic functions and all hemodynamic and
      microvascular changes. In addition, Hb-200 resuscitation in hypovolemic dogs
      (approximately 40% blood loss) did not cause extreme hemodilution or fatal
      outcome. This study confirms that real-time (in vivo) microvascular studies,
      which were conducted only in small rodent models in the past, can be performed
      simultaneously with systemic function, hemodynamic, and oxygenation studies in a
      large animal model for relevant data correlation. IMPLICATIONS: This is the first
      time that changes in the blood circulation have been studied, quantified, and
      correlated with systemic function, hemodynamic, and oxygenation changes in shock
      and during shock treatment in a large animal model. This study was performed by a
      new technology developed in-house to noninvasively and quantitatively study blood
      vessels in real time.

PMID- 11574343
TI  - Jugular bulb oxyhemoglobin desaturation, S100beta, and neurologic and cognitive
      outcomes after coronary artery surgery.
AB  - We reported that a decline in cognitive performance 3 mo after coronary artery
      bypass grafting surgery is associated with palpable aortic atheroma, but not
      postoperative jugular bulb oxyhemoglobin saturation (SjO2) <50%. However, the
      effect of SjO2 on clinical neurologic findings is not known. S100beta is a
      possible surrogate biochemical marker of brain injury, and we report here the
      scored clinical neurologic findings in 98 patients from our previous study in
      relation to SjO2, cognitive performance, aortic atheroma, and S100beta. Patients
      underwent a scored neurologic examination and cognitive assessment the day before
      and 3 mo after coronary artery bypass grafting surgery. Intraoperatively,
      intermittent blood sampling was performed, and postoperatively, the area under
      the curve describing SjO2 <50% in relation to time was calculated from continuous
      jugular bulb reflectance oximetry. Palpation was used to assess the ascending
      aorta for the presence of atheroma. The jugular bulb concentration of S100beta
      was measured 6 h after completion of surgery. The neurologic score 3 mo after
      surgery did not correlate with either intra- or postoperative SjO2 (r = 0.111, P
      = 0.278; and r = -0.074, P = 0.467, respectively). The main determinant of
      neurologic score at 3 mo was the preoperative neurologic score (r(2) = 0.63, P <
      0.001), whereas palpable atheroma of the ascending aorta made a small but
      significant contribution (r(2) = 0.034, P = 0.004). Neurologic and cognitive
      scores correlated before surgery (r = 0.226, P = 0.022) and at 3 mo after surgery
      (r = 0.348, P < 0.001). A preoperative neurologic deficit of two or more had a
      small but significant negative effect on cognitive performance at 3 mo
      (standardized beta = -0.097, P = 0.018). There was a significant univariate
      correlation between S100beta and the 3-mo neurologic score (r = -0.232, P <
      0.05), but not a multivariate correlation (beta = -0.090, P = 0.156).
      IMPLICATIONS: Intraoperative jugular bulb oxyhemoglobin saturation (SjO2) and
      postoperative SjO2 <50% do not have an important influence on long-term
      neurologic outcome after coronary artery bypass graft surgery. Subtle
      preoperative neurology is associated with long-term cognitive decline, and aortic
      atheroma is a risk factor for both cognitive and neurologic decline.

PMID- 11574344
TI  - Isoproterenol enhances myofilament Ca(2+) sensitivity during hypothermia in
      isolated guinea pig beating hearts.
AB  - Isoproterenol is often required to treat acute left ventricular dysfunction
      during separation from cardiopulmonary bypass for cardiac surgery. We
      hypothesized that heart rate and intracellular Ca(2+) concentration ([Ca(2+)]i)
      homeostasis may be important factors when isoproterenol improves the cardiac
      function during hypothermia. Accordingly, we investigated the effect of
      isoproterenol on the cardiac functional variables, [Ca(2+)]i, and myofilament
      Ca(2+) sensitivity under spontaneous beating during hypothermia. Intact guinea
      pig hearts were perfused with a modified Krebs-Ringer solution (baseline) and
      Krebs-Ringer solution containing isoproterenol (1 nM) at 37 degrees C, 32 degrees
      C, and 27 degrees C while all cardiac variables and [Ca(2+)]i were recorded.
      Isoproterenol increased developed left ventricular pressure (LVP), maximum rate
      of increase in LVP, and coronary inflow at 27 degrees C, and it also increased
      heart rate and maximum rate of decrease in LVP at each temperature (P < 0.05).
      Isoproterenol produced a leftward shift of the curve of developed LVP as a
      function of available [Ca(2+)]i at 32 degrees C and 27 degrees C (P < 0.05),
      without changing available [Ca(2+)]i. Isoproterenol improves the cardiac
      function, especially systolic ventricular function, by enhancement of myofilament
      Ca(2+) sensitivity under spontaneous beating during hypothermia in intact guinea
      pig hearts. IMPLICATIONS: Enhancement of myofilament Ca(2+) sensitivity is
      involved in the improvement of cardiac function by isoproterenol under
      spontaneous beating during hypothermia.

PMID- 11574345
TI  - Epidural analgesia reduces postoperative myocardial infarction: a meta-analysis.
AB  - Postoperative cardiac morbidity and mortality continue to pose considerable risks
      to surgical patients. Postoperative epidural analgesia is considered to have
      beneficial effects on cardiac outcomes. The use in high-risk cardiac patients
      remains controversial. No study has shown that postoperative epidural analgesia
      decreases postoperative myocardial infarction (PMI) or death. All studies are
      underpowered to show such a result, and the cost of conducting a large trial is
      prohibitive. We performed a metaanalysis to determine whether postoperative
      epidural analgesia continued for more than 24 h after surgery reduces PMI or in
      hospital death. The available databases were searched for randomized controlled
      trials of epidural analgesia that was extended at least 24 h into the
      postoperative period. The search yielded 17 studies, of which 11 were randomized
      controlled trials comprising 1173 patients. Metaanalysis was conducted by using
      the fixed-effects model, calculating both an odds ratio and a rate difference.
      Postoperative epidural analgesia resulted in better analgesia for the first 24 h
      after surgery. The rate of PMI was 6.3%, with lower rates in the Epidural group
      (rate difference, -3.8%; 95% confidence interval [CI] -7.4%, -0.2%; P = 0.049).
      The frequency of in-hospital death was 3.3%, with no significant difference
      between Epidural and Nonepidural groups (rate difference, -1.3%; 95% CI, -3.8%,
      1.2%, P = 0.091). Subgroup analysis of postoperative thoracic epidural analgesia
      showed a significant reduction in PMI in the Epidural group (rate difference, 
      5.3%; 95% CI, -9.9%, -0.7%; P = 0.04). IMPLICATIONS: Postoperative epidural
      analgesia, especially thoracic epidural analgesia, continued for more than 24 h
      reduces postoperative myocardial infarctions.

PMID- 11574346
TI  - A comparison of fentanyl, sufentanil, and remifentanil for fast-track cardiac
      anesthesia.
AB  - Cardiac surgery is estimated to cost $27 billion annually in the United States.
      In an attempt to decrease the costs of cardiac surgery, fast-track programs have
      become popular. The purpose of this study was to compare the effects of three
      different opioid techniques for cardiac surgery on postoperative pain, time to
      extubation, time to intensive care unit discharge, time to hospital discharge,
      and cost. Ninety adult patients undergoing cardiac surgery were randomized to a
      fentanyl-based, sufentanil-based, or remifentanil-based anesthetic. Postoperative
      pain was measured at 30 min after extubation and at 6:30 AM on the first
      postoperative day. Pain scores at both times were similar in all three groups (P
      > 0.05). Median ventilator times of 167, 285, and 234 min (P > 0.05), intensive
      care unit stays of 18.8, 19.8, and 21.5 h (P > 0.05), and hospital stays of 5, 5,
      and 5 days (P > 0.05) for the Fentanyl, Sufentanil, and Remifentanil groups did
      not differ. Three patients needed to be tracheally reintubated: two in the
      Sufentanil group and one in the Fentanyl group. Median anesthetic costs were
      largest in the Remifentanil group ($140.54 [$113.54-$179.29]) and smallest in the
      Fentanyl group ($43.33 [$39.36-$56.48]) (P < or = 0.01), but hospital costs were
      similar in the three groups: $7841 (Fentanyl), $5943 (Sufentanil), and $6286
      (Remifentanil) (P > 0.05). We conclude that the more expensive but shorter-acting
      opioids, sufentanil and remifentanil, produced equally rapid extubation, similar
      stays, and similar costs to fentanyl, indicating that any of these opioids can be
      recommended for fast-track cardiac surgery. IMPLICATIONS: To conserve resources
      for cardiac surgery, fentanyl-, sufentanil-, and remifentanil-based anesthetics
      were compared for duration of mechanical ventilation, intensive care unit length
      of stay, hospital length of stay, and cost. The shorter-acting anesthetics,
      sufentanil and remifentanil, produced equally rapid extubation, similar stays,
      and similar costs to fentanyl; thus, any of these opioids can be recommended for
      fast-track cardiac surgery.

PMID- 11574347
TI  - Conscious sedation with midazolam or propofol does not alter left ventricular
      diastolic performance in patients with preexisting diastolic dysfunction: a
      transmitral and tissue Doppler transthoracic echocardiography study.
AB  - The effects of midazolam and propofol on left ventricular (LV) diastolic function
      have not been evaluated in humans. We tested the hypothesis that midazolam and
      propofol alter LV diastolic function evaluated with transmitral and tissue
      Doppler transthoracic echocardiography in patients with normal LV systolic
      function in the presence and absence of preexisting diastolic dysfunction. After
      IRB approval and informed consent, patients (n = 34) with normal or reversed
      transmitral blood flow velocity E-to-A ratios received 3 escalating doses of
      midazolam (0.025, 0.05, and 0.1 mg/kg) or propofol (0.25, 0.5, and 1.0 mg/kg)
      over 10 s at 5-min intervals. Hemodynamic variables and indices of diastolic
      function were recorded 3 min after each dose of midazolam and propofol. Patients
      with diastolic dysfunction demonstrated decreased ratios of peak transmitral E-to
      A wave velocity and their corresponding time-velocity integrals as compared with
      normal patients. Reductions in anterior and posterior mitral annulus E/A ratios
      were also present. Midazolam and propofol did not further alter indices of LV
      diastolic function in patients with impaired early LV filling. The results
      indicate that sedation with midazolam or propofol does not affect indices of LV
      diastolic performance in healthy patients and those with preexisting diastolic
      dysfunction. IMPLICATIONS: Sedation with midazolam or propofol does not alter
      indices of left ventricular diastolic function in healthy patients and those with
      preexisting left ventricular filling abnormalities as evaluated by transthoracic
      echocardiography.

PMID- 11574348
TI  - Loss of physiologic hepatic blood flow control ("hepatic arterial buffer
      response") during CO2-pneumoperitoneum in the rat.
AB  - We analyzed whether a compensatory increase of hepatic arterial (HA) flow, known
      as the "hepatic arterial buffer response" (HABR), may serve for maintenance of
      liver blood supply during laparoscopy-associated portal venous (PV) flow
      reduction. We assessed HA and PV flow, as well as hepatic tissue oxygenation
      (PO2) during CO2-pneumoperitoneum in anesthetized and mechanically ventilated
      Sprague-Dawley rats (n = 7). Control animals (n = 7) without pneumoperitoneum,
      but tourniquet-induced PV flow reduction served to demonstrate physiologic HABR.
      Although stepwise tourniquet-induced reduction of PV flow to 20% of baseline
      values led to a significant (P < 0.05) increase of HA flow from 4.3 +/- 0.7
      mL/min to 9.9 +/- 1.7 mL/min, stepwise intraabdominal pressure-induced decrease
      of PV flow was paralleled by a linear reduction of HA flow from 2.4 +/- 0.3
      mL/min to 1.2 +/- 0.5 mL/min at 18 mm Hg intraabdominal pressure. This loss of
      HABR was sustained during a subsequent 2 h-period of CO2-pneumoperitoneum
      contrasting the 2 h of maintenance of HABR in controls. Hepatic tissue PO2
      decreased during the 2 h-period of pressure- and tourniquet-induced PV flow
      reduction by 35% to 51%, respectively. On tourniquet release, all variables
      regained baseline values, whereas evacuation of the pneumoperitoneum allowed all
      variables except hepatic PO2 to return to baseline, indicating prolonged tissue
      hypoxia despite restored total liver blood flow in the Laparoscopic group.
      Concomitantly, increased liver enzyme activities reflected moderate tissue damage
      after 2 h of pneumoperitoneum. In conclusion, intraabdominal CO2-insufflation
      induced hemodynamic alterations may impair tissue oxygenation and enzyme release,
      indicating the potential risk for hepatic tissue damage after prolonged periods
      of laparoscopic interventions. IMPLICATIONS: We investigated the effect of CO2
      pneumoperitoneum on liver blood flow, hepatic tissue oxygenation (PO2) and liver
      enzyme release. CO2-insufflation reduces portal venous flow without a
      compensatory increase of hepatic arterial flow ("hepatic arterial buffer
      response"), resulting in reduced hepatic PO2 and increased ratios of serum
      alanine aminotransferase to serum aspartate aminotransferase.

PMID- 11574349
TI  - Bleeding in a patient receiving platelet aggregation inhibitors.
AB  - IMPLICATIONS: We describe a patient who experienced intraoperative bleeding after
      being treated with platelet receptor glycoprotein IIb/IIIa antagonist
      eptifibatide. We used Sonoclot and Thrombelastograph to monitor antiplatelet
      effects of eptifibatide.

PMID- 11574350
TI  - The optimal length of insertion of central venous catheters for pediatric
      patients.
AB  - Incorrect positioning of central venous catheters (CVC) in infants and children
      may lead to serious complications such as perforation of the heart or great
      vessels. CVC position is not usually assessed until the first postoperative chest
      radiograph, potentially leaving malposition undetected for several hours. We
      studied a series of 452 right internal jugular and subclavian catheter placements
      in infants and children undergoing surgery for congenital heart disease, and
      measured the distance from the skin insertion site to the radiographic junction
      of the superior vena cava and right atrium (RA). Based on these data, the
      following formulae predict that a CVC will be positioned above the RA 97% of the
      time: correct length of insertion (cm) = (height in cm/10) - 1 for patients < or
      =100 cm in height, and (height in cm/10) - 2 for patients >100 cm in height.
      Weight-based recommendations were also developed which predict placement of CVC
      above the RA 98% of the time. IMPLICATIONS: This study assessed central venous
      catheter placement in 452 infants and children undergoing cardiac surgery.
      Simple, clinically useful guidelines based on height and weight were developed to
      prevent malposition of these catheters, which may cause serious complications
      such as perforation of the heart or great vessels.

PMID- 11574351
TI  - Hemostatic changes in pediatric neurosurgical patients as evaluated by
      thrombelastograph.
AB  - Thromboembolic events are a known complication in neurosurgical patients. There
      is evidence to suggest that a hypercoagulable state may develop perioperatively.
      Thrombelastograph (TEG) coagulation analysis is a reliable method of evaluating
      hypercoagulability. We evaluated coagulation by using TEG data in pediatric
      neurosurgical patients undergoing craniotomy to determine whether a
      hypercoagulable state develops intraoperatively or postoperatively. Thirty
      children undergoing craniotomy for removal of a tumor or seizure focus were
      studied. Blood was analyzed with TEG) data by using native and celite techniques,
      at three time points for each patient: preoperatively after induction of
      anesthesia; intraoperatively during closure of the dura; and on the first
      postoperative day. Compared with preoperative indices, closing and postoperative
      celite TEG values were indicative of hypercoagulability with shortened
      coagulation time values (P < 0.001), prolonged alpha angle divergence values (P <
      0.001), and above-normal TEG coagulation indices (P < or = 0.002). Reaction time
      values were shortened, and maximal amplitude of clot strength values were
      prolonged but did not reach statistical significance. Hypercoagulation develops
      early after resection of brain tissue in pediatric neurosurgical patients as
      assessed by using TEG data. Further studies are needed to determine the clinical
      significance of this hypercoagulable state. IMPLICATIONS: Hypercoagulability in
      postoperative neurosurgical patients has been demonstrated in the adult
      population, but few studies have dealt with the pediatric population. We found
      that children undergoing craniotomy for focal resection, lobectomy, and
      hemispherectomy are hypercoagulable as detected by thrombelastograph coagulation
      analysis. Further studies are needed to determine whether this is clinically
      significant.

PMID- 11574352
TI  - The pharmacokinetics of epidural ropivacaine in infants and young children.
AB  - The pharmacokinetic variables of ropivacaine were characterized after epidural
      bolus injection in pediatric patients. The subjects, 7 infants (aged 3-11 mo) and
      11 young children (aged 12-48 mo), received 1.7 mg/kg of ropivacaine via a lumbar
      epidural catheter. Total plasma concentrations of ropivacaine measured over 24 h
      were assayed by high-pressure liquid chromatography, and pharmacokinetic modeling
      was performed by Nonlinear Mixed Effects Modeling analysis. The median peak
      venous plasma concentrations (C(max)) in infants and young children were 610
      microg/L (interquartile range [IQR], 550-725 microg/L) and 640 microg/L (IQR, 540
      750 microg/L), respectively. The median times to maximum plasma ropivacaine
      concentration (T(max)) were 60 min (IQR, 60-120 min) in infants and 60 min (IQR,
      30-90 min) in young children. There were no statistical differences between
      median values of C(max) and T(max) between infants and young children. The
      calculated clearance (CL) in infants was 4.26 mL x min(-1) x kg(-1) (9%
      coefficient of variation), and in young children it was 6.15 mL x min(-1) x kg(
      1) (11% coefficient of variation). The CL for infants was significantly less than
      the CL for young children (P < 0.01). The volume of distribution was estimated to
      be 2370 mL/kg (9% coefficient of variation) for both young children and infants.
      No systemic toxicity was observed in either group. IMPLICATIONS: This study
      revealed that the pharmacokinetic variables of lumbar epidural bolus ropivacaine
      in pediatric patients aged 3 to 48 mo are similar to those of adults, except that
      drug clearance was less in infants compared with older children.

PMID- 11574353
TI  - Salbutamol prevents the increase of respiratory resistance caused by tracheal
      intubation during sevoflurane anesthesia in asthmatic children.
AB  - Asthmatic children having their tracheas intubated with sevoflurane often have an
      increase in respiratory system resistance (Rrs). In this randomized, placebo
      controlled, double-blinded study, we investigated the protective effect of an
      inhaled beta2-adrenergic agonist. Either salbutamol or placebo was administered
      30 to 60 min before anesthesia to 30 mildly to moderately asthmatic children
      scheduled for elective surgery. Induction was performed with sevoflurane in a
      mixture of 50% nitrous oxide in oxygen and maintained at 3%, with children
      breathing spontaneously via a face mask and Jackson-Rees modification of the T
      piece. Airway opening pressure and flow were measured before and after insertion
      of an oral endotracheal tube. Rrs and respiratory system compliance were
      calculated with multilinear regression analysis. The groups were comparable with
      respect to age, weight, asthma history, and breathing pattern. Intubation induced
      a different Rrs response in the two groups: children treated with salbutamol
      showed a 6.0% (-25.2% to +13.2%) decrease (mean, 95% confidence interval),
      whereas in the Placebo group there was a 17.7% (+4.4% to +30.9%) increase (P =
      0.04). Neither asthma history nor the serum inflammation marker eosinophilic
      cationic protein was predictive for this response. We conclude that when using
      sevoflurane in mildly to moderately asthmatic children, a preanesthetic treatment
      with inhaled salbutamol is protective of an increase in Rrs. IMPLICATIONS:
      Tracheal intubation with sevoflurane as the sole anesthetic is now often
      performed in children. It can induce an increase in respiratory system resistance
      in children with asthma. This study shows that in children with mild to moderate
      asthma, a preanesthetic treatment with inhaled salbutamol can prevent the
      increase of respiratory system resistance.

PMID- 11574354
TI  - Anesthetic management of acquired tracheoesophageal fistula: a brief report.
AB  - IMPLICATIONS: Tracheoesophageal fistula may be either a congenital lesion or an
      acquired condition, most often resulting from foreign body ingestion. Location of
      the lesion has implications for anesthetic management and single lung ventilation
      may be required to facilitate surgical repair. In pediatric patients, intentional
      mainstem intubation may be required.

PMID- 11574355
TI  - The effect of timing of dolasetron administration on its efficacy as a
      prophylactic antiemetic in the ambulatory setting.
AB  - Dolasetron (12.5 mg IV) is effective in both preventing and treating
      postoperative nausea and vomiting (PONV) after ambulatory surgery. However, the
      optimal timing of dolasetron administration and its effect on the patient's
      quality of life after discharge have not been established. One-hundred-five
      healthy, consenting women undergoing gynecologic laparoscopic procedures with a
      standardized general anesthetic technique were enrolled in this randomized,
      double-blinded study. Group 1 received dolasetron 12.5 mg IV 10-15 min before the
      induction of anesthesia; Group 2 received dolasetron 12.5 mg IV at the end of the
      laparoscopy (79 +/- 48 min later than Group 1); and Group 3 received dolasetron
      12.5 mg IV at the end of anesthesia (93 +/- 52 min later than Group 1). The
      incidence of PONV, complete responses (defined as no emetic episodes and no
      rescue medication within the 24-h period after anesthesia), recovery profiles,
      and patient satisfaction were recorded. In the postanesthesia care unit and
      during the 24-h follow-up period, the incidence of nausea and vomiting, as well
      as the need for rescue antiemetics, did not differ significantly among the three
      groups. The percentages of patients with complete responses to the study drug
      within the first postoperative 24 h were also similar in all three groups (55%,
      59%, and 52% for Groups 1, 2, and 3, respectively). The early and intermediate
      recovery profiles, including resumption of a normal diet and patient satisfaction
      with the control of PONV, were not different among the three study groups.
      Dolasetron 12.5 mg IV administered before the induction of anesthesia is as
      effective as dolasetron given at the end of laparoscopy or at the end of
      anesthesia in preventing PONV after outpatient laparoscopy. IMPLICATIONS: The
      timing of dolasetron administration appears to have little effect on its efficacy
      when administered as a prophylactic antiemetic in the ambulatory setting.

PMID- 11574356
TI  - Music decreases sedative requirements during spinal anesthesia.
AB  - Ambulatory surgery can create significant anxiety. This prospective study
      measured whether music can influence anxiety and perioperative sedative
      requirements in outpatients undergoing surgery with spinal anesthesia. We also
      evaluated the correlation between two anxiety measures, the State-Trait Anxiety
      Inventory test (STAI) and the 0- to 10-cm visual analog scale (VAS 0-10), with 0
      meaning complete relaxation and 10 the worst feeling of anxiety possible. Fifty
      unpremedicated patients were randomly assigned to listen to music of their choice
      via headset during the perioperative period (Group I) or to have no music (Group
      II). All participants used patient-controlled IV midazolam sedation and underwent
      repeated evaluations of their anxiety level with the STAI and the VAS 0-10.
      Midazolam requirements during surgery (Group I, 0.6 +/- 0.7 versus Group II, 1.3
      +/- 1.1 mg; P < 0.05) and for the whole perioperative period (Group I, 1.2 +/-
      1.3 versus Group II, 2.5 +/- 2.0 mg; P < 0.05) were smaller in patients listening
      to music. Anxiety levels, measured with STAI or VAS 0-10, were similar in both
      groups. The Spearman's coefficient values between STAI and VAS 0-10 ranged from
      0.532 to 0.687. We conclude that patients listening to music require less
      midazolam to achieve a similar degree of relaxation as controls and that measures
      of anxiety obtained from the STAI and the VAS 0-10 are positively, but only
      moderately, correlated. IMPLICATIONS: It is possible to decrease sedative
      requirements during surgery under spinal anesthesia by allowing patients to
      listen to music to reduce their anxiety.

PMID- 11574357
TI  - Ambulatory surgery: room air versus nasal cannula oxygen during transport after
      general anesthesia.
AB  - We compared outpatients transported to the postanesthesia care unit (PACU) while
      breathing room air to 2-4 L/min nasal cannula oxygen (O2) to test the hypothesis
      that routine supplemental O2 during transport is not required after general
      anesthesia in an ambulatory surgery center. We also examined whether the
      arbitrary arrival PACU O2 saturations of > 92% may be used to predict an
      infrequent incidence of subsequent significant desaturations (< 90%) in the PACU.
      One-hundred-ninety patients were randomized to receive either room air or 2-4
      L/min nasal cannula for transport to PACU after receiving general anesthesia. O2
      saturations were recorded before surgery, just before leaving the operating room,
      and upon arrival in the PACU. The lowest O2 saturation occurring in the PACU was
      also recorded. The mean arrival PACU O2 saturation was 95.0 in the Room Air
      group, compared with 97.2 for the Nasal Cannula (NC) group, a statistically
      significant difference (P < 0.001). In the Room Air group, 20% had arrival O2
      saturations < or = 92%, and half of these (10%) had O2 saturations < 90%. In the
      NC group, 6% had O2 saturations < or = 92%, of which one third (2%) were < 90% on
      arrival in the PACU. All of these initial desaturations were easily corrected
      with face-tent O2 administration, deep breathing, or both. Subgroup analysis
      revealed that patients whose ages were 60 yr or older or those weighing 100 kg or
      more had lower arrival room air saturations than their younger or slimmer
      counterparts. In the Room Air group, only three (3.9%) of the patients that
      arrived in PACU with O2 saturations > 92% had subsequent desaturations < 90%,
      compared with seven (7.9%) in the NC group. We conclude that most adult patients
      undergoing ambulatory surgery can be transported safely to the PACU breathing
      room air after general anesthesia. However, patients whose age was > or = 60 yr
      or weight was > or = 100 kg, or for whom transient O2 desaturation on transport
      may be harmful, should be transported while breathing nasal O2 via nasal cannula.
      IMPLICATIONS: Most adult patients undergoing ambulatory surgery can be
      transported safely to the PACU breathing room air after general anesthesia.
      However, patients whose age was > or = 60 yr or weight > or = 100 kg, or for whom
      transient O2 desaturation on transport may be harmful, should be transported
      while breathing oxygen via nasal cannula.

PMID- 11574358
TI  - The convulsant and anesthetic properties of cis-trans isomers of 1,2
      dichlorohexafluorocyclobutane and 1,2-dichloroethylene.
AB  - The differences in potencies of optical isomers of anesthetics support the
      hypothesis that anesthetics act by specific receptor interactions.
      Diastereoisomerism and geometrical isomerism offer further tests of this
      hypothesis but have not been explored. They are the subject of this report. We
      quantified the nonimmobilizing and convulsant properties of the cis and trans
      diastereomers of the nonimmobilizer 2N (1,2-dichlorohexafluorocyclobutane).
      Although the lipophilicity of the diastereomers predicts complete anesthesia at
      the partial pressures applied, neither diastereomer had anesthetic activity
      alone, and the cis form may have a small (10%) capacity to antagonize anesthesia,
      as defined by additive effects on the MAC (the minimum alveolar concentration
      required to suppress movement to a noxious stimulus in 50% of rats) of
      desflurane. Both diastereomers produced convulsions, the cis form being nearly
      twice as potent as the trans form: convulsant 50% effective dose (mean +/- SD)
      was 0.039 +/- 0.009 atmospheres (atm) for the purified cis and 0.064 +/- 0.009
      atm for the purified trans isomer. The MAC value for cis-1,2-dichloroethylene
      equaled 0.0071 +/- 0.0006 atm, and MAC for trans-1,2-dichloroethylene equaled
      0.0183 +/- 0.0031 atm. In qualitative accord with the Meyer-Overton hypothesis,
      the greater cis potency was associated with a greater lipophilicity. However, the
      product of MAC x solubility differed between the cis and trans isomers by 40%
      50%. We conclude that neither the cis nor trans isomers of 2N have anesthetic
      properties, but isomerism does influence 2N's convulsant properties and the
      anesthetic properties of dichloroethylene. These isomeric effects may be as
      useful in defining receptor-anesthetic interactions as those found with optical
      isomers. IMPLICATIONS: Cis-trans isomerism can influence the convulsant
      properties of the nonimmobilizer 2N (1,2-dichlorohexafluorocyclobutane) and the
      anesthetic properties of dichloroethylene. Such isomeric effects may be as useful
      as those found with optical isomers in defining receptor-anesthetic interactions.

PMID- 11574359
TI  - The role of drug-lipid interactions on the disposition of liposome-formulated
      opioid analgesics in vitro and in vivo.
AB  - Although liposome encapsulation prolongs the duration of action of epidurally
      administered drugs, little is known about how liposome encapsulation affects
      opioids differently, or about how lipid content of liposomes alters the
      bioavailability of epidurally-administered opioids. To address these issues,
      morphine, alfentanil, fentanyl, and sufentanil were loaded into D-alpha
      dipalmitoyl phosphatidylcholine multilamellar liposomes, and incorporation
      efficiency and in vitro release rates were determined. We then determined
      epidural morphine and sufentanil liposomes, at two different lipid/opioid ratios,
      in vivo in a pig model in which epidural and intrathecal spaces were continuously
      sampled via microdialysis. Liposome encapsulation efficiency was significantly
      more for sufentanil (100%) than for the other opioids (25%-30%). The in vitro
      release rate was slowest for morphine, intermediate for fentanyl and alfentanil,
      and fastest for sufentanil. In vivo, morphine was released more slowly than
      sufentanil. It is most important to note that increasing the lipid content of
      morphine liposomes increased the proportion of drug reaching the intrathecal
      space. In contrast, increasing the lipid content of sufentanil liposomes did not
      alter intrathecal movement but did decrease movement into plasma. Therefore,
      increasing drug hydrophobicity and lipid content of the liposomes modulates drug
      distribution in vivo. IMPLICATIONS: The degree of interaction between opioids and
      lipid bilayers in liposome-formulated opioids dictates the rates at which
      epidurally-administered drugs distribute into the intrathecal compartment and
      blood in potentiating analgesic effects.

PMID- 11574360
TI  - Induction of anesthesia with ketamine reduces the magnitude of redistribution
      hypothermia.
AB  - Hypothermia after induction of general anesthesia results largely from core-to
      peripheral redistribution of body heat. Both central inhibition of tonic
      thermoregulatory vasoconstriction in arteriovenous shunts and anesthetic-induced
      arteriolar and venous dilation contribute to this redistribution. Ketamine,
      unique among anesthetics, increases peripheral arteriolar resistance; in
      contrast, propofol causes profound venodilation that other anesthetics do not. We
      therefore tested the hypothesis that induction of anesthesia with ketamine causes
      less core hypothermia than induction with propofol. Twenty patients undergoing
      elective surgery were randomly assigned to anesthetic induction with either 1.5
      mg/kg ketamine (n = 10) or 2.5 mg/kg propofol (n = 10). Anesthesia in both groups
      was subsequently maintained with sevoflurane and 60% nitrous oxide in oxygen.
      Forearm minus finger, skin-temperature gradients <0 degrees C were considered
      indicative of significant arteriovenous shunt vasodilation. Ketamine did not
      cause vasodilation just after induction, whereas propofol rapidly induced
      vasodilation. Core temperatures in the patients given ketamine remained
      significantly greater than those in the patients induced with propofol. These
      data suggest that maintaining vasoconstriction during induction of anesthesia
      reduces the magnitude of redistribution hypothermia. IMPLICATIONS: Core
      hypothermia during the first hour of anesthesia was less after induction of
      anesthesia with ketamine than propofol. Maintaining arteriovenous shunt
      vasoconstriction during induction of anesthesia reduces the magnitude of
      redistribution hypothermia.

PMID- 11574361
TI  - The concentration-effect relationship of the respiratory depressant effects of
      alfentanil and fentanyl.
AB  - The relative potencies of fentanyl and alfentanil for respiratory depression were
      determined in eight healthy male volunteers in a double-blinded, randomized study
      with a cross-over design. The drugs were delivered by computer-driven infusion
      with logarithmically ascending plasma concentrations until the respiratory rate
      reached 2/min and/or oxygen saturation decreased below 85% with subjects
      breathing room air. Ventilation was measured with respiratory inductive
      plethysmography, indirect calorimetry, and arterial blood gas analysis, and
      plasma drug concentrations were determined. Pharmacodynamic modeling was
      performed using a fractional E(max) model for minute volume and respiratory rate
      and the concentrations producing 50% depression (i.e., apparent 50% effective
      concentration [EC(50)] values) were determined. Both drugs decreased ventilation
      in a similar manner, and drug infusions were terminated at mean +/- SD measured
      plasma concentrations of 254 +/- 88 ng/mL and 5.1 +/- 1.7 ng/mL for alfentanil
      and fentanyl, respectively. Alfentanil decreased minute volume from baseline by
      54% +/- 19% and respiratory rate by 40% +/- 11% with EC(50) values of 234 +/- 57
      ng/mL and 195 +/- 101 ng/mL. The respective decreases for fentanyl were 50% +/-
      11%, 41% +/- 15%, and the estimated EC(50) values were 6.1 +/- 1.4 ng/mL and 3.5
      +/- 1.4 ng/mL, respectively. Using the apparent EC(50) values, the calculated
      potency ratio for alfentanil:fentanyl was (mean and 95% confidence interval) 1:39
      (1:31-1:46) for minute volume and 1:51 (1:34-1:68) for respiratory rate. This is
      analogous to the analgesic effect studied earlier. The findings support the
      notion of parallel analgesic and respiratory depressant effects of alfentanil and
      fentanyl. Therefore equianalgesic concentrations of both drugs will lead to
      equally pronounced respiratory depression. IMPLICATIONS: This double-blinded,
      randomized study evaluated the potency ratio of alfentanil and fentanyl-induced
      respiratory depression. The findings support the notion of parallel analgesic and
      respiratory depressant effects of alfentanil and fentanyl. Therefore
      equianalgesic concentrations of both drugs will lead to equally pronounced
      respiratory depression.

PMID- 11574362
TI  - Age, minimum alveolar anesthetic concentration, and minimum alveolar anesthetic
      concentration-awake.
AB  - Two defining effects of inhaled anesthetics (immobility in the face of noxious
      stimulation, and absence of memory) correlate with the end-tidal concentrations
      of the anesthetics. Such defining effects are characterized as MAC (the
      concentration producing immobility in 50% of patients subjected to a noxious
      stimulus) and MAC-Awake (the concentration suppressing appropriate response to
      command in 50% of patients; memory is usually lost at MAC-Awake). If the
      concentrations are monitored and corrected for the effects of age and
      temperature, the concentrations may be displayed as multiples of MAC for a
      standard age, usually 40 yr. This article provides an algorithm that might be
      used to produce such a display, including provision of an estimate of the effect
      of nitrous oxide. IMPLICATIONS: Two defining effects of inhaled anesthetics
      (immobility in the face of noxious stimulation, and absence of memory) correlate
      with the end-tidal concentrations of the anesthetics. Thus, these defining
      effects may be monitored and the results displayed if the concentrations are
      known and corrected for the effects of age and temperature.

PMID- 11574363
TI  - Reexamined: the recommended endotracheal intubating dose for nondepolarizing
      neuromuscular blockers of rapid onset.
AB  - The results of any study of the relative importance of anesthetic depth versus
      intensity of neuromuscular block on conditions for endotracheal intubation can be
      manipulated by the investigator. Several independent factors, such as the depth
      of hypnosis induced, the interval between drug administration and laryngoscopy,
      the onset profile of the muscle relaxant, and the multiple of the 95% effective
      dose given, must be controlled. We attempted to design an induction sequence that
      provided good to excellent conditions for laryngoscopy and endotracheal
      intubation within 75-90 s of muscle relaxant administration with doses smaller
      than often suggested, while still administering only customary amounts of
      hypnotics and opioids. Alfentanil 12.5 microg/kg, propofol 2.0 mg/kg, and a test
      drug were administered rapidly. The test drugs were saline 0.05 mL/kg (n = 10),
      rapacuronium 1.0 or 1.2 mg/kg, or rocuronium 0.50 mg/kg (n = 30 each).
      Laryngoscopy was commenced 75 s after the test drug. Clinically acceptable
      conditions for intubation were achieved in all subjects after rocuronium or
      rapacuronium 1.2 mg/kg and in 28 of 30 patients after rapacuronium 1.0 mg/kg. In
      the Saline group, only 3 individuals achieved a good or excellent rating, and
      intubation was impossible in 2 of 10 individuals. For muscle relaxants of low
      potency, doses only 1.5 times the 95% effective dose can provide very
      satisfactory conditions for intubation if laryngoscopy is delayed to 75 s after
      drug administration. IMPLICATIONS: The dose of muscle relaxant usually
      recommended for facilitating tracheal intubation approximates at least two times
      the drug's effective dose (ED(95)). When the muscle relaxant in question has a
      rapid onset of action, this intubation dose may be decreased to 1.5 times the
      ED(95).

PMID- 11574365
TI  - Practical issues in bispectral analysis of electroencephalographic signals.
AB  - IMPLICATIONS: The aim of this report was to confirm the methodology of bispectral
      analysis of electroencephalogram. In developing a software for real-time
      bispectral analysis, we encountered several practical problems in bispectrum
      calculation. We settled those and concluded that 3 min of monitoring are required
      to obtain reliable and reproducible bicoherence values.

PMID- 11574364
TI  - Fire in the operating room: a case report and laboratory study.
AB  - In July, 1998 a fire occurred in an operating room (OR) at the University Medical
      Center in Tucson, AZ. A patient was burned on the face, neck, and shoulders by
      the fire, which started during cranial burr-hole placement under monitored
      anesthesia care. This paper describes the actual case in some detail. The
      incident was simulated as accurately as possible in a laboratory experiment, in
      an attempt to determine specific risk factors for this event. The experiment
      found that a specific combination of factors was required to produce a fire
      similar in appearance to the one in the OR. The risk factors determined in these
      experiments are discussed in the context of previous reports of OR fires.
      Although other reports demonstrate some common characteristics of these events,
      the fire at the University Medical Center appears to be unique within the
      literature regarding the specific chain of events that led up to it.
      IMPLICATIONS: A patient was seriously burned in a fire that occurred during
      surgery. We performed laboratory experiments to re-create the fire, and found
      some of the key factors that led to this event.

PMID- 11574366
TI  - The inability to detect expired carbon dioxide after endotracheal intubation as a
      result of one-way valve obstruction of the endotracheal tube.
AB  - IMPLICATIONS: Failure to tracheally intubate and ventilate the lungs is a major
      cause of anesthesia morbidity. Expired carbon dioxide monitoring has become a
      standard for assessing correct endotracheal tube placement. We present a case of
      failure to detect expired carbon dioxide after successful intubation resulting
      from a one-way valve obstruction of the endotracheal tube.

PMID- 11574367
TI  - Hypercapnia related to a faulty adult co-axial breathing circuit.
AB  - IMPLICATIONS: This report describes the appearance of CO2 on the capnograph
      during inspiration, which was linked to disconnection of the inner tube of a
      coaxial circuit extension piece. The increased use of coaxial breathing systems
      for adults makes inner tubes disconnections an important consideration when the
      CO2 appears during inspiration.

PMID- 11574368
TI  - Carpal tunnel syndrome in female nurse anesthetists versus operating room nurses:
      prevalence, laterality, and impact of handedness.
AB  - Nurse anesthesia may be a high-risk occupation for carpal tunnel syndrome (CTS)
      in the workplace. We designed a cross-sectional investigation to study the
      prevalence of CTS in nurse anesthetists (NAs) as compared with operating room
      nurses (ORNs). Two-hundred forty-four female operating room workers were
      classified by job title as NAs (n = 63) and ORNs (n = 181). The case definition
      of CTS was established by a history of surgical correction or a combination of
      four positive historical and physical findings. There were 10 cases of CTS in NAs
      and 10 cases of CTS in ORNs. The crude odds ratio (OR) for CTS in NAs was 3.23
      (95% confidence interval, 1.27-8.17, P = 0.021). The crude OR for left-hand CTS
      in NAs was also 3.23 and 3.58 for bilateral CTS. When adjusted for nondominant
      left-hand or bilateral CTS, the OR for CTS in NAs was 3.85. The Yates-corrected
      chi(2) for CTS in NAs was 5.346 (P = 0.021) and 5.075 (P = 0.024) for nondominant
      left-hand or bilateral CTS in NAs as compared with ORNs. On the basis of our data
      analysis, nondominant left-hand CTS and bilateral CTS were significantly more
      prevalent in NAs than ORNs. IMPLICATIONS: Repetitive stress injuries have now
      exceeded back injuries as the most commonly reported workplace injuries in the
      United States. Female nurse anesthetists may face greater occupational risks for
      developing left hand and bilateral carpal tunnel syndrome than female operating
      room nurses.

PMID- 11574369
TI  - Oxidative stress status during exposure to propofol, sevoflurane and desflurane.
AB  - We evaluated the circulating and lung oxidative status during general anesthesia
      established with propofol, sevoflurane, or desflurane in mechanically ventilated
      swine. Blood samples and bronchoalveolar lavage fluid (BAL) specimens were
      respectively performed via an internal jugular vein catheter and a
      nonbronchoscopic BAL for baseline oxidative activity measurements:
      malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase
      (GPX). A 4-h general anesthesia was then performed in the three groups of 10
      swine: the Propofol group received 8 mg x kg(-1) x h(-1) of IV propofol as the
      sole anesthetic; the Desflurane group received 1.0 minimum alveolar concentration
      of desflurane; and the Sevoflurane group received 1.0 minimum alveolar
      concentration of sevoflurane. We observed significantly larger levels of MDA in
      plasma and BAL during desflurane exposure than with the other anesthetics. We
      also observed smaller concentrations of circulating GPX and alveolar GPX. We
      found a significant decrease for MDA measurements in the plasma and the pulmonary
      lavage during propofol anesthesia. We also found larger values of GPX
      measurements in the serum and the pulmonary lavage. No significant changes were
      observed when animals were exposed to sevoflurane. No significant changes were
      found for circulating concentrations of SOD during exposure to all anesthetics.
      In this mechanically ventilated swine model, desflurane seemed to induce a local
      and systemic oxidative stress, whereas propofol and sevoflurane were more likely
      to have antioxidant properties. IMPLICATIONS: Superoxide is an unavoidable
      byproduct of oxygen metabolism that occurs in various inflammatory reactions.
      Inhalation of volatile anesthetics under mechanical ventilation induces an
      inflammatory response. We evaluated the bronchoalveolar and systemic oxidative
      stress in swine during exposure to propofol and newer volatile anesthetics.
      Desflurane induces more lipid peroxidation than do the other anesthetics.

PMID- 11574370
TI  - Epidural labor analgesia and neonatal sepsis evaluation rate: a quality
      improvement study.
AB  - Labor epidural analgesia (LEA) is allegedly associated with maternal fever and an
      increase in the newborn sepsis work-up (SWU) rate. In this study, we evaluated
      whether LEA causes an increase in the SWU rate compared with a Control group
      given parenteral narcotics for labor pain. Maternal and neonatal data were
      collected prospectively for a continuous quality improvement database. Odds
      ratios were calculated by using multiple logistic regression for various triggers
      for SWU in the neonate. Of the 1177 primiparous women and their neonates studied,
      922 women received LEA and 255 women received parenteral analgesics. A small but
      statistically significant increase in maternal and neonatal temperatures occurred
      in parturients receiving LEA. The SWU rates were 7.5% in the LEA group and 9.4%
      in the Controls (not significant). Triggers identified for SWU were birth weight
      (odds ratio = 116, P = 0.000), gestational age (odds ratio = 86.6, P = 0.000),
      meconium aspiration and respiratory distress requiring intubation (odds ratio =
      8.6, P = 0.000), hypothermia at birth (odds ratio = 7.1, P = 0.001), maternal
      Group B beta-hemolytic streptococcal colonization (odds ratio = 6, P = 0.000),
      and preeclampsia or hypertension (odds ratio = 3.5, P = 0.03). There was no
      association between LEA and SWU. IMPLICATIONS: Although it has been suggested
      that epidural analgesia for labor contributes to an increase in neonatal sepsis
      work-up (SWU), this retrospective analysis shows that epidural analgesia is not
      associated with an increase in SWU. The factors that were found to contribute to
      SWU included low birth weight, low gestational age, meconium aspiration or
      respiratory distress at birth, hypothermia at birth, maternal group B beta
      hemolytic colonization, and preeclampsia or hypertension.

PMID- 11574371
TI  - The anesthetic management of triplet cesarean delivery: a retrospective case
      series of maternal outcomes.
AB  - Spinal anesthesia for the cesarean delivery of triplets is associated with an
      increased incidence of maternal hypotension and placental hypoperfusion. We
      performed a retrospective case series analysis between January 1992 and June 2000
      to evaluate the effects of regional anesthetic techniques for cesarean delivery
      in triplet pregnancies on maternal and neonatal outcome. Spinal and epidural
      anesthesia were compared with respect to intraoperative hemodynamics and neonatal
      outcomes. Ninety-six triplet pregnancies were delivered by cesarean section, of
      which 91 received regional anesthesia. A statistically significant decrease in
      systolic blood pressure was demonstrated immediately after the induction of
      spinal as compared with epidural anesthesia. The total volume of IV crystalloid
      used was significantly larger in the Spinal Anesthesia group. The number of
      patients receiving more than 15 mg of ephedrine and the cumulative dose of
      ephedrine was significantly larger in the Spinal group compared with the Epidural
      group. There were no differences in the rate of perioperative complications
      between the Spinal and Epidural Anesthesia groups. Neonatal Apgar scores were
      similar in both groups. The data suggest that both epidural and spinal anesthesia
      for triplet cesarean delivery are safe techniques, but the latter is associated
      with a larger initial decrease in systolic blood pressure. This decreasing of
      systolic blood pressure, however, remained within the physiological range and did
      not seem to be clinically significant. The need for more crystalloid fluids and
      ephedrine should be anticipated when spinal anesthesia is used for these cases.
      IMPLICATIONS: A large retrospective case series of the effects of spinal and
      epidural anesthesia on maternal hemodynamic profile during cesarean delivery for
      triplet gestation was performed. Our findings suggest that spinal anesthesia
      results in outcomes comparable to epidural anesthesia for both mother and
      newborns.

PMID- 11574372
TI  - Levobupivacaine combined with sufentanil and epinephrine for intrathecal labor
      analgesia: a comparison with racemic bupivacaine.
AB  - We performed a randomized, double-blinded study to compare levobupivacaine with
      racemic bupivacaine for labor analgesia. Eighty term parturients received either
      levobupivacaine 0.125% or racemic bupivacaine 0.125%, to which was added
      sufentanil 0.75 microg/mL and epinephrine 1.25 microg/mL. As part of a combined
      spinal-epidural procedure, 2 mL of this mixture was initially injected
      intrathecally, and the same solutions were subsequently administered epidurally.
      For both combinations, onset until the first painless contraction was 4 to 5 min.
      Most patients were pain free during the second contraction. The duration of
      initial spinal analgesia was 93.5 +/- 20 min and 94.7 +/- 31 min for
      levobupivacaine and racemic bupivacaine, respectively. The duration of analgesia
      for the first epidural top-up dose was also similar in the two groups. Total
      local anesthetic requirements during labor were not different. The only major
      difference observed was the absence of motor impairment in levobupivacaine
      treated parturients as compared with the Racemic Bupivacaine group, in which the
      incidence of a Bromage-1 motor block was 34%. Other side effects and obstetric or
      neonatal outcomes were not different between groups. Intrathecal levobupivacaine
      has a similar clinical profile as racemic bupivacaine, but at equal doses it
      produced less motor block. IMPLICATIONS: When used intrathecally and epidurally
      for labor analgesia, levobupivacaine had the same clinical profile as racemic
      bupivacaine, but at equal doses it produced less motor block.

PMID- 11574373
TI  - The influence of a bupivacaine and fentanyl epidural infusion after epidural
      fentanyl in patients allowed to ambulate in early labor.
AB  - Epidural fentanyl after a lidocaine and epinephrine test dose provides adequate
      analgesia and allows for ambulation during early labor. This study was designed
      to determine the influence of an epidural infusion of bupivacaine plus fentanyl
      administered after initiation of epidural labor analgesia with fentanyl.
      Specifically, we evaluated whether there is an increase in motor block or an
      increased time to request for further analgesic medication. Fifty-one laboring
      primigravid women at <5 cm cervical dilation who requested epidural analgesia
      were enrolled. After a 3-mL epidural test dose of 1.5% lidocaine with epinephrine
      (5 microg/mL), patients received fentanyl 100 microg via the epidural catheter.
      They then randomly received either an infusion (10 mL/h) of 0.0625% bupivacaine
      with fentanyl (3 microg/mL) or an infusion of preservative-free saline. After the
      administration of the initial analgesic, pain scores and side effects were
      recorded for each patient at 10, 20, and 30 min, every 30 min thereafter, and at
      the time of request for additional analgesic medication, by an observer blinded
      to the technique used. There were no demographic differences between the two
      groups. The mean duration of analgesia (time from initial dose to request for
      additional analgesia) was increased in the group that received a continuous
      infusion of bupivacaine and fentanyl compared with the Saline group (198 +/- 86
      vs 145 +/- 50 min; P < 0.009). Side effects were similar between the two groups.
      No patient in either group experienced any detectable motor block. Fourteen
      patients chose to ambulate in the Saline group, and 12 patients chose to ambulate
      in the Infusion group. In early laboring patients, a continuous infusion of
      0.0625% bupivacaine infusion with fentanyl (3 microg/mL) prolonged the duration
      until top-up was required, after epidural fentanyl 100 microg after a lidocaine
      and epinephrine test dose, and did not cause any clinically detectable motor
      block. IMPLICATIONS: A 0.0625% bupivacaine and fentanyl (3 microg/mL) infusion,
      when added to epidural fentanyl (100 microg), prolongs the analgesic duration
      without increasing motor block in women in early labor.

PMID- 11574374
TI  - Intrathecal morphine for postpartum tubal ligation postoperative analgesia.
AB  - Intrathecal morphine (ITM) provides effective postoperative cesarean delivery
      analgesia but has not been reported for postoperative postpartum tubal ligation
      (PPTL) analgesia. We designed this prospective, randomized, double-blinded study
      to determine the efficacy of 100 microg ITM for postoperative PPTL analgesia.
      Sixty-six women received spinal anesthesia with 60 mg (1.2 mL) of 5% hyperbaric
      lidocaine, 10 microg (0.2 mL) of fentanyl, and either 0.2 mL of 0.9% saline
      (normal saline; NS) or 100 microg (0.2 mL) of morphine (morphine sulfate, MS).
      Postoperative analgesia was limited to patient-controlled IV analgesia morphine.
      Six women (three NS and three MS) were excluded because of major protocol
      violations. Twenty-four-hour patient-controlled IV analgesia morphine use was
      (mean +/- SD) 39.6 +/- 19.6 mg in the NS group and 1.1 +/- 2.5 mg in the MS group
      (P < 0.0000001). Visual analog scale scores for crampy and incisional pain (rest
      and movement) were significantly higher in the NS group compared with the MS
      group at 4, 8, 12, and 24 h (P < 0.001). The adverse effect profile was similar
      between groups. Visual analog scale satisfaction scores (mean +/- SD) were 96.6
      +/- 16.0 in the MS group and 84.2 +/- 23.6 in NS group (P < 0.05). The results of
      this study indicate that women experience significant postoperative pain after
      PPTL surgery, and this pain is effectively obviated by 100 microg ITM.
      IMPLICATIONS: This investigation documents the extent of the significant
      postoperative pain experienced by women after routine postpartum tubal ligation
      surgery and demonstrates the efficacy of a small dose (100 microg) of intrathecal
      morphine to obviate this pain with minimal adverse effects.

PMID- 11574375
TI  - A prostaglandin E2 receptor subtype EP1 receptor antagonist (ONO-8711) reduces
      hyperalgesia, allodynia, and c-fos gene expression in rats with chronic nerve
      constriction.
AB  - Chronic constriction injury (CCI) of the sciatic nerve in rats induces persistent
      mechanical hyperalgesia and allodynia. CCI is widely known as a model of
      neuropathic pain, and many studies using this model have been reported. Recently,
      c-fos has been used as a neural marker of pain, and various studies have assessed
      the relationship between hyperalgesia and c-fos expression in the lumbar spinal
      cord. In this study, we examined the role of a prostaglandin E2 receptor subtype
      EP1 receptor antagonist (ONO-8711) in a rat CCI model. EP1 receptor antagonist
      (EP1-ra) oral administration from day 8 to day 14 significantly reduced
      hyperalgesia and allodynia in the three pain tests on day 15. EP1-ra treatment
      from day 8 to 14 also reduced c-fos-positive cells in laminae I-II, III-IV, and V
      X compared with saline treatment. A single dose of EP1-ra treatment on day 8
      significantly reduced hyperalgesia and allodynia at 1 h and 2 h after
      administration, but the efficacy was not observed at 24 h. We conclude that EP1
      ra treatment may be useful for hyperalgesia and allodynia and that EP1 receptor
      mechanisms are involved in the maintenance of c-fos gene expression induced by
      nerve injury. IMPLICATIONS: We examined whether a prostaglandin E2 receptor
      subtype EP1 receptor antagonist abrogates neuropathic pain induced by chronic
      constriction injury model in rats. The EP1 receptor antagonist significantly
      reduced hyperalgesia, allodynia, and c-fos positive cells. These findings
      suggested that EP1 receptor antagonists may have a role in treatment of
      neuropathic pain.

PMID- 11574376
TI  - The synergistic antinociceptive interactions of endomorphin-1 with
      dexmedetomidine and/or S(+)-ketamine in rats.
AB  - Spinal administration of the endogenous mu-opioid agonist peptide, endomorphin-1,
      results in antinociception in rodents, but there are few data about its
      interaction with other antinociceptive drugs. We investigated the antinociceptive
      interactions at the spinal level of endomorphin-1 with the N-methyl-D-aspartate
      antagonist S(+)-ketamine, the alpha2-adrenoceptor agonist dexmedetomidine, or
      both in awake rats. Nociception was assessed by the tail-flick test. Dose
      response curves were determined for endomorphin-1 (0.6-50 microg), for
      dexmedetomidine (0.1-10 microg), for mixtures of S(+)-ketamine (30 or 100 microg)
      with endomorphin-1 (2-18 microg) or of endomorphin-1 with dexmedetomidine in a
      fixed ratio (4:1), and for the triple combination of the three drugs after
      intrathecal administration. Endomorphin-1 and dexmedetomidine both produced dose
      dependent antinociception. The coadministration of 100 microg S(+)-ketamine
      significantly enhanced the antinociceptive effect of 6 microg endomorphin-1.
      Isobolographic analysis of the combinations of endomorphin-1 and dexmedetomidine
      revealed a synergistic interaction between these drugs. The 80% effective dose
      for the triple combination was significantly less than that for either binary
      combination. These data indicate that S(+)-ketamine and dexmedetomidine, acting
      via different receptors, produce synergistic antinociceptive interaction with
      endomorphin-1 at the spinal level. Furthermore, the triple combination of an
      opioid agonist, an alpha2-adrenoceptor agonist, and an N-methyl-D-aspartate
      receptor antagonist shows potent antinociceptive activity. IMPLICATIONS: The
      coadministration of the N-methyl-D-aspartate antagonist receptor antagonist, S(+)
      ketamine, or the specific alpha2-adrenoceptor agonist, dexmedetomidine,
      significantly enhances the antinociceptive effect of the endogenous mu-opioid
      agonist, endomorphin-1, at the spinal level. The triple combination of the three
      drugs causes a further improved antinociception.

PMID- 11574377
TI  - The synergistic interaction between midazolam and clonidine in spinally-mediated
      analgesia in two different pain models of rats.
AB  - Both midazolam, a benzodiazepine gamma-aminobutyric acid type A receptor agonist,
      and clonidine, an alpha2-adrenergic receptor agonist, induce spinally-mediated
      analgesia. We investigated the analgesic interaction of spinally-administered
      midazolam and clonidine in their effects on acute and inflammatory nociception.
      Rats implanted with lumbar intrathecal catheters were injected intrathecally with
      saline (control), midazolam (1 to 100 microg), or clonidine (0.1 to 3 microg) to
      test for their responses to thermal stimulation to the tail (tail-flick test) and
      subcutaneous formalin injection into the hind paw (formalin test). The effects of
      the combination of midazolam and clonidine on both stimuli were tested by
      isobolographic analysis by using the 50% effective doses. The general behavior
      and motor function were examined as side effects. When combined, the 50%
      effective doses of midazolam (clonidine) decreased from 1.57 microg (0.26 microg)
      to 0.29 g (0.05 microg) in the tail-flick test and from 1.34 microg (0.12 microg)
      and 1.21 microg (0.13 microg) to 0.05 microg (0.005 microg) and 0.13 microg
      (0.015 microg) in Phase 1 and 2 of the formalin test, respectively. Side effects
      did not increase by using the combination. These results suggest a favorable
      combination of intrathecal midazolam and clonidine in the management of acute and
      inflammatory pain after proper neurotoxicologic studies. IMPLICATIONS: Spinally
      administered midazolam, a benzodiazepine, and clonidine, an alpha2-adrenergic
      receptor agonist, have significant synergistic effects on thermally-induced acute
      and formalin-induced inflammatory pain.

PMID- 11574378
TI  - The long-term antinociceptive effect of intrathecal S(+)-ketamine in a patient
      with established morphine tolerance.
AB  - IMPLICATIONS: Our report describes for the first time the continuous long-term
      intrathecal application of S(+)-ketamine in a patient with chronic pain and
      morphine tolerance. Intrathecally applied S(+)-ketamine led to a significant pain
      reduction and consecutively reduced the doses of intrathecal morphine required
      for pain relief even several weeks after the cessation of the 24-day period of
      intrathecal S(+)-ketamine administration.

PMID- 11574379
TI  - The placement of the epidural catheter at the predicted site by electrical
      stimulation test.
AB  - More accurate segmental and sagittal positioning of the epidural catheter tip is
      required for the success of continuous epidural analgesia, spinal cord
      monitoring, and percutaneous epidural spinal cord stimulation. We examined the
      usefulness of an electrical stimulation test for verifying the proper placement
      of the epidural catheter tip at the predicted site in the posterior epidural
      space by using a locally developed epidural catheter with electrodes at its tip.
      The test included the observation of segmental bilateral muscle twitches and the
      patient's report of feeling in the region stimulated by moving the epidural
      catheter electrode back and forth and changing the direction of the bevel of the
      Tuohy needle. The success rate of midline placement at the required spinal
      segment was significantly more frequent (99%; P < 0.001) in the group (n = 289)
      receiving the electrical stimulation test compared with the group (n = 277) not
      receiving the test (success rate 57%). The results indicate the usefulness of
      this method. We concluded that the electrical stimulation test is effective for
      verifying the proper placement of the catheter electrode tip. IMPLICATIONS:
      Ideally the epidural catheter tip should be positioned in the posterior epidural
      space near the midline. We concluded that the electrical stimulation test is
      effective for verifying the proper placement of the catheter electrode tip.

PMID- 11574380
TI  - A new posterior approach to the sciatic nerve block: a prospective, randomized
      comparison with the classic posterior approach.
AB  - To evaluate the efficacy and acceptance of a new posterior subgluteus approach to
      the sciatic nerve, as compared with the classic posterior approach, 128 patients
      undergoing foot orthopedic procedures were randomly allocated to receive either
      the classic posterior sciatic nerve block (Group Labat, n = 64) or a modified
      subgluteus posterior approach (Group subgluteus, n = 64). All blocks were
      performed with the use of a nerve stimulator (stimulation frequency, 2 Hz;
      intensity, 1-0.5 mA). In Group subgluteus, a line was drawn from the greater
      trochanter to the ischial tuberosity; then, from the midpoint of this line, a
      second line was drawn perpendicularly and extended caudally for 4 cm. The end of
      this line represented the needle entry. In both groups, a proper sciatic
      stimulation was elicited at 0.5 mA; then 20 mL of 0.75% ropivacaine was injected.
      The time from needle insertion to successful sciatic nerve stimulation was 60 s
      (range, 10-180 s) with the Labat's approach and 32 s (range, 5-120 s) with the
      new subgluteus approach (P = 0.0005). The depth of appropriate sciatic
      stimulation was 45 +/- 13 mm (mean +/- SD) after 2 (range, 1-7) needle
      redirections in Group subgluteus and 67 +/- 12 mm after 4 (range, 1-10) needle
      redirections in Group Labat (P = 0.0001 and P = 0.00001, respectively). The
      failure rate was similar in both groups. Severe discomfort during the procedure
      was less frequent and acceptance better in Group subgluteus (5 patients [8%] and
      60 patients [94%], respectively) than in Group Labat (20 patients [31%] and 49
      patients [77%], respectively) (P = 0.0005 and P = 0.005, respectively). We
      conclude that this new subgluteus posterior approach to the sciatic nerve is an
      easy and reliable technique and can be considered an effective alternative to the
      more traditional Labat's approach. IMPLICATIONS: Evaluating the efficacy and
      acceptance of a new approach to the sciatic nerve block, this prospective,
      randomized study demonstrated that the new subgluteus posterior approach is an
      easy and reliable technique and can be considered an useful alternative to the
      more traditional Labat's approach in patients undergoing foot surgery,
      facilitating the performance of the sciatic nerve blocks.

PMID- 11574381
TI  - The continuous femoral nerve block catheter for postoperative analgesia:
      bacterial colonization, infectious rate and adverse effects.
AB  - We investigated the incidence of bacterial and vascular or neurological
      complications resulting from femoral nerve catheters used for postoperative
      analgesia. Patients requiring continuous femoral blockade were consecutively
      included. Using surgical aseptic procedure, 211 femoral nerve catheters were
      placed (short-beveled insulated needle, peripheral nerve stimulator). After 48 h,
      each catheter was removed and semiquantitative bacteriological cultures were
      performed on each distal catheter tip. Postoperative analgesia and antibiotics
      were standardized. All complications during the insertion of the catheters and
      postoperatively (after 48 h and 6 wk) were noted. Few initial complications with
      no immediate or delayed complications were noted (20 difficult insertions, 3
      impossible injections, 3 ineffective catheters, and 12 vascular punctures). After
      48 h, 208 catheters were analyzed; 57% had positive bacterial colonization (with
      a single organism in 53%). The most frequent organisms were Staphylococcus
      epidermidis (71%), Enterococcus (10%), and Klebsiella (4%). Neither cellulitis
      nor abscess occurred. Three transitory bacteremias likely related to the catheter
      occurred. After 6 wk, no septic complications were noted. One femoral
      paresthesia, partially recovered 1 yr later, was noted. We conclude that the risk
      of bacterial complications is small with femoral nerve catheters, although the
      rate of colonization is frequent. IMPLICATIONS: In this prospective study,
      continuous femoral nerve catheters were effective for postoperative analgesia but
      had a frequent rate of bacterial catheter colonization. We found no serious
      infections after short-term (2-day) infusion. Side effects were few, but one
      nerve injury occurred.

PMID- 11574382
TI  - The addition of epinephrine to tetracaine injected intrathecally sustains an
      increase in glutamate concentrations in the cerebrospinal fluid and worsens
      neuronal injury.
AB  - We have reported that large concentrations of intrathecal tetracaine increase
      glutamate concentrations in the cerebrospinal fluid (CSF) and cause neuronal
      injury in the spinal cord. In this study, we investigated whether the addition of
      epinephrine to tetracaine modulates these events. New Zealand white rabbits were
      assigned into five groups (six rabbits in each group) and intrathecally received
      0.3 mL of epinephrine 0.1 mg/mL in NaCl solution (control), 1% tetracaine
      dissolved in saline (1%T), 1% tetracaine with epinephrine (1%TE), 2% tetracaine
      (2%T), or 2% tetracaine with epinephrine (2%TE). Glutamate concentrations in the
      lumbar CSF were monitored by microdialysis. Neurologic and histopathologic
      assessments were performed 1 wk after the administration. Glutamate
      concentrations significantly increased in all four groups that received
      tetracaine, whereas no change was observed in the Control group. The addition of
      epinephrine to tetracaine sustained large concentrations of glutamate. Sensory
      and motor dysfunction was observed in the 1%TE, 2%T, and 2%TE groups, and the
      dysfunction tended to be progressively exacerbated in this order. Characteristic
      histologic changes in animals with sensory and motor dysfunction were vacuolation
      in the dorsal funiculus and chromatolytic damage of motor neurons. The
      vacuolation of the dorsal funiculus in the 1%TE group was significantly worse
      than in the 1%T group. These results suggest that the addition of epinephrine to
      tetracaine may increase its neurotoxicity, which may possibly be related to a
      sustained increase of glutamate concentrations in the CSF. IMPLICATIONS:
      Sustained increase of glutamate concentrations produced by the addition of
      epinephrine to intrathecal tetracaine can cause neuronal injury.

PMID- 11574383
TI  - Anatomic relations between the cephalic vein and the sensory branches of the
      radial nerve: How can nerve lesions during vein puncture be prevented?
AB  - The cephalic vein of the forearm is often used for IV catheters because of its
      ease of access for peripheral venous cannulation. But its close relation to the
      sensory branch of the radial nerve sometimes causes it to be damaged when the
      vein is cannulated. Our anatomic study conducted on 33 specimens confirmed the
      risk of nerve lesion. However, it is impossible to define a safe zone, because of
      the randomly located nerve and vein crossing zones, where the iatrogenic risk of
      damaging the radial nerve is maximum. We suggest that to avoid incidents, the
      cephalic vein should be punctured above the emergence of the sensory branch of
      the radial nerve, e.g., at least 12 cm above the level of the styloid process of
      the radius. IMPLICATIONS: We attempted to determine the relationship between the
      cephalic vein and the sensory branch of the radial nerve at the wrist to help
      prevent lesions of the radial nerve when the cephalic vein is cannulated. We
      examined the anatomy of 33 postmortem specimens and suggest that puncture of the
      cephalic vein 12 cm or more proximal to the styloid process can prevent radial
      nerve lesions.

PMID- 11574384
TI  - The prevalence and predictors of the use of alternative medicine in presurgical
      patients in five California hospitals.
AB  - We measured the prevalence and predictors of the use of alternative medicine
      supplements in surgical patients by way of a self-administered questionnaire in
      consecutive patients > or = 18 yr old awaiting elective noncardiac surgery at
      five San Francisco Bay Area Hospitals. A total of 2560 patients completed the
      study survey (60% response rate). Of these patients, 39.2% admitted to using some
      form of alternative medicine supplements, of which herbal medicine was the most
      common type (67.6%). Of those who admitted to taking alternative medicine
      supplements, 44.4% did not consult with their primary physicians, and 56.4% did
      not inform the anesthesiologists before surgery regarding their use of these
      products; 53% of the patients ceased the use of these products before surgery.
      Multivariate logistic regression analysis revealed the following variables to be
      associated with the preoperative use of herbal medicine: female sex (odds radio
      [OR] 1.42, confidence interval [CI] 1.17-1.72), age 35-49 yr (OR 1.25, CI 1.02
      1.53), higher income levels (OR 1.85, CI 1.50-2.27), Caucasian race (OR 1.34, CI
      1.07-1.67), higher level of education (OR 1.35, CI 1.10-1.65), problems with
      sleep (OR 1.32, CI 1.05-1.66), problems with joints or back (OR 1.27, CI 1.04
      1.56), allergies (OR 1.48, CI 1.21-1.82), problems with addiction (OR 1.90, CI
      1.25-2.89), and a history of general surgery (OR 1.25, CI 1.03-1.52). In
      contrast, diabetes mellitus (OR 0.55, CI 0.36-0.86) and the use of antithrombotic
      medications (OR 0.57, CI 0.38-0.87) were associated with decreased odds of the
      use of herbal medicines. We concluded that the use of alternative medicine
      supplements by surgical patients is prevalent. Documentation of the use of these
      products is critical to determine the potential of drug or anesthetic
      interactions in the perioperative period. IMPLICATIONS: The use of alternative
      medicine supplements by presurgical patients is prevalent. Documentation of the
      use of these products is critical to determine the potential of drug or
      anesthetic interactions in the perioperative period.

PMID- 11574385
TI  - The influence of the laryngeal mask airway on the shape of the submandibular
      gland.
AB  - Although transient sialadenopathy of the submandibular gland associated with
      insertion of the laryngeal mask airway (LMA) has been described, the influence of
      the LMA on the submandibular gland is unknown. We measured the width and length
      of the submandibular glands by using ultrasonography in patients in whom the LMA
      was used. An increased intracuff pressure of the LMA, up to 150 cm H2O, was used
      in a prospective study of adult patients scheduled for elective surgery. The
      width of the gland increased with an increasing intracuff pressure from 50 to 100
      cm H2O (P < 0.01) and 100 to 150 cm H2O (P < 0.01) but did not change from 0 to
      50 cm H2O. There was no change in the length of the gland. We conclude that the
      submandibular gland was deformed by the insertion of the LMA. IMPLICATIONS: The
      findings in our study show that the submandibular triangle can be easily
      compressed by the insertion of the laryngeal mask airway (LMA). When inserting
      the LMA, it is important to consider that the LMA cuff may alter these tissues,
      which are situated between the lingual root and the submandibular triangle.

PMID- 11574386
TI  - The incidence of class "zero" airway and the impact of Mallampati score, age,
      sex, and body mass index on prediction of laryngoscopy grade.
AB  - IMPLICATIONS: In an earlier study we proposed the addition of a new airway class,
      zero (visualization of the epiglottis), to the four classes of the modified
      Mallampati classification. In this prospective study, 764 surgical patients were
      assessed with regard to their airway class (including class zero), laryngoscopy
      grade, and the effect of the airway class and other predictors on the
      laryngoscopy grade.

PMID- 11574387
TI  - The anesthetic management of a case of tracheogastric fistula.
AB  - IMPLICATIONS: A 68-yr-old man developed a tracheogastric fistula after esophageal
      resection with gastric interposition. We report the anesthetic management of this
      patient undergoing tracheal repair and fistula closure.

PMID- 11574388
TI  - Comparing the articulating laryngoscope and external laryngeal manipulation.

PMID- 11574389
TI  - Preoperative use of colforsin daropate hydrochloride in a patient with severe
      cardiac function scheduled for Y-graft replacement.

PMID- 11574390
TI  - Current perception thresholds do not vary significantly.

PMID- 11574391
TI  - How can we possibly prevent complications related to peripheral nerve blocks?

PMID- 11574392
TI  - Venous double cannulation: avoiding complications.

PMID- 11574393
TI  - Neuromuscular blockers and awareness.

PMID- 11574394
TI  - Blindness associated with severe preeclampsia/eclampsia.

PMID- 11574395
TI  - "Soap bubbles" and "gauze thread" drain tube tests.

PMID- 11574396
TI  - Gene and cell-replacement therapy in the treatment of type 1 diabetes: how high
      must the standards be set?
AB  - Recent advances in molecular and cell biology may allow for the development of
      novel strategies for the treatment and cure of type 1 diabetes. In particular, it
      is now possible to envisage restoration of insulin secretion by gene or cell
      replacement therapy. The beta-cell is, however, remarkably sophisticated, and
      many of the features of this highly differentiated secretory cell will have to be
      faithfully mimicked in surrogate cells. In particular, insulin is normally
      secreted in a well-regulated fashion in rapid response to the metabolic needs of
      the individual and most specifically (but not exclusively) to changes in
      circulating levels of glucose. Such regulated secretion will be indispensable in
      order to avoid both hyper- and hypoglycemic episodes and depends on the ability
      of cells to store insulin in secretory granules before exocytosis in response to
      physiological stimuli. Furthermore, any newly created insulin-secreting cell will
      have to be able to adapt to alterations in insulin requirements that accompany
      changes with exercise, body weight, and aging. Fine tuning of insulin secretion
      over the longer term will also be important to avoid "clinical shifting" that
      could be caused by over-insulinization, including increased adiposity and
      cardiovascular disease. Finally, it will be necessary to ensure that newly
      created or implanted (surrogate) beta-cells are protected in some way from
      recognition by the immune system and in particular from autoimmune destruction.

PMID- 11574397
TI  - Insulin activates ATP-sensitive K(+) channels in pancreatic beta-cells through a
      phosphatidylinositol 3-kinase-dependent pathway.
AB  - Insulin is known to regulate pancreatic beta-cell function through the activation
      of cell surface insulin receptors, phosphorylation of insulin receptor substrate
      (IRS)-1 and -2, and activation of phosphatidylinositol (PI) 3-kinase. However, an
      acute effect of insulin in modulating beta-cell electrical activity and its
      underlying ionic currents has not been reported. Using the perforated patch clamp
      technique, we found that insulin (1-600 nmol/l) but not IGF-1 (100 nmol/l)
      reversibly hyperpolarized single mouse beta-cells and inhibited their electrical
      activity. The dose-response relationship for insulin yielded a maximal change
      (mean +/- SE) in membrane potential of -13.6 +/- 2.0 mV (P < 0.001) and a 50%
      effective dose of 25.9 +/- 0.1 nmol/l (n = 63). Exposing patched beta-cells
      within intact islets to 200 nmol/l insulin produced similar results,
      hyperpolarizing islets from -47.7 +/- 3.3 to -65.6 +/- 3.7 mV (P < 0.0001, n =
      11). In single cells, insulin-induced hyperpolarization was associated with a
      threefold increase in whole-cell conductance from 0.6 +/- 0.1 to 1.7 +/- 0.2 nS
      (P < 0.001, n = 10) and a shift in the current reversal potential from -25.7 +/-
      2.5 to -63.7 +/- 1.0 mV (P < 0.001 vs. control, n = 9; calculated K(+)
      equilibrium potential = -90 mV). The effects of insulin were reversed by
      tolbutamide, which decreased cell conductance to 0.5 +/- 0.1 nS and shifted the
      current reversal potential to -25.2 +/- 2.3 mV. Insulin-induced beta-cell
      hyperpolarization was sufficient to abolish intracellular calcium concentration
      ([Ca(2+)](i)) oscillations measured in pancreatic islets exposed to 10 mmol/l
      glucose. The application of 100 nmol/l wortmannin to inactivate PI 3-kinase, a
      key enzyme in insulin signaling, was found to reverse the effects of 100 nmol/l
      insulin. In cell-attached patches, single ATP-sensitive K(+) (K(ATP)) channels
      were activated by bath-applied insulin and subsequently inhibited by wortmannin.
      Our data thus demonstrate that insulin activates the K(ATP) channels of single
      mouse pancreatic beta-cells and islets, resulting in membrane hyperpolarization,
      an inhibition of electrical activity, and the abolition of [Ca(2+)](i)
      oscillations. We thus propose that locally released insulin might serve as a
      negative feedback signal within the islet under physiological conditions.

PMID- 11574398
TI  - Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator
      activated receptor-gamma action in humans.
AB  - Recent studies in murine models suggest that resistin (also called Fizz3 [1]), a
      novel cysteine-rich protein secreted by adipocytes, may represent the long-sought
      link between obesity and insulin resistance (2). Furthermore, peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) agonists appear to inhibit
      resistin expression in murine adipocytes, providing a possible explanation for
      the mode of action of this class of insulin sensitizers (2). Using a fluorescent
      real-time reverse transcriptase-polymerase chain reaction-based assay, we found
      that resistin mRNA levels in whole adipose tissue samples were increased in
      morbidly obese humans compared with lean control subjects. However, in freshly
      isolated human adipocytes, resistin mRNA levels were very low and showed no
      correlation with BMI. Resistin mRNA was undetectable in preadipocytes,
      endothelial cells, and vascular smooth muscle cells, but it was readily
      detectable in circulating mononuclear cells. Although exposure of human
      mononuclear cells to PPAR-gamma agonists markedly upregulated fatty acid-binding
      protein-4 expression, these agents had no effect on mononuclear cell resistin
      expression. Finally, resistin mRNA was undetectable in adipocytes from a severely
      insulin-resistant subject with a dominant-negative mutation in PPAR-gamma (3). We
      conclude that the recently described relationships of murine resistin/Fizz3
      expression with obesity, insulin resistance, and PPAR-gamma action may not
      readily translate to humans. Further studies of this novel class of proteins are
      needed to clarify their roles in human metabolism.

PMID- 11574399
TI  - The effect of insulin on in vivo cerebral glucose concentrations and rates of
      glucose transport/metabolism in humans.
AB  - The continuous delivery of glucose to the brain is critically important to the
      maintenance of normal metabolic function. However, elucidation of the hormonal
      regulation of in vivo cerebral glucose metabolism in humans has been limited by
      the lack of direct, noninvasive methods with which to measure brain glucose. In
      this study, we sought to directly examine the effect of insulin on glucose
      concentrations and rates of glucose transport/metabolism in human brain using
      (1)H-magnetic resonance spectroscopy at 4 Tesla. Seven subjects participated in
      paired hyperglycemic (16.3 +/- 0.3 mmol/l) clamp studies performed with and
      without insulin. Brain glucose remained constant throughout (5.3 +/- 0.3
      micromol/g wet wt when serum insulin = 16 +/- 7 pmol/l vs. 5.5 +/- 0.3 micromol/g
      wet wt when serum insulin = 668 +/- 81 pmol/l, P = NS). Glucose concentrations in
      gray matter-rich occipital cortex and white matter-rich periventricular tissue
      were then simultaneously measured in clamps, where plasma glucose ranged from 4.4
      to 24.5 mmol/l and insulin was infused at 0.5 mU. kg(-1). min(-1). The
      relationship between plasma and brain glucose was linear in both regions.
      Reversible Michaelis-Menten kinetics fit these data best, and no differences were
      found in the kinetic constants calculated for each region. These data support the
      hypothesis that the majority of cerebral glucose uptake/metabolism is an insulin
      independent process in humans.

PMID- 11574400
TI  - A role for protein phosphatase 2A-like activity, but not atypical protein kinase
      Czeta, in the inhibition of protein kinase B/Akt and glycogen synthesis by
      palmitate.
AB  - We have shown previously that palmitate treatment of C2C12 skeletal muscle
      myotubes causes inhibition of the protein kinase B (PKB) pathway and hence
      reduces insulin-stimulated glycogen synthesis through the elevation of
      intracellular ceramide levels. Ceramide is known to activate both atypical
      protein kinase C (aPKC) zeta and protein phosphatase (PP) 2A, and each of these
      effectors has been reported to inhibit PKB. In the present study, palmitate
      pretreatment was found to elevate PP2A-like activity in myotubes and to prevent
      its inhibition by insulin. Incubation with the phosphatase inhibitor okadaic acid
      before insulin stimulation protected against the effect of the fatty acid on PKB
      phosphorylation. Palmitate was unable to inhibit PKB activity and glycogen
      synthesis in cells overexpressing the activated PKB mutant (T308D,S473D)
      PKBalpha, which is unaffected by phosphatase. In contrast, PKB activity and
      glycogen synthesis were still inhibited by palmitate in cells overexpressing a
      membrane-targeted and, hence, activated PKB mutant that retains sensitivity to
      phosphatase. Although aPKC activity was also increased in palmitate-treated
      cells, overexpression of wild-type or kinase-dead aPKCzeta did not alter the
      inhibitory effects of the lipid on either stimulation of PKB or glycogen
      synthesis by insulin. We conclude that palmitate disrupts insulin signaling in
      C2C12 myotubes by promoting PP2A-like activity and, therefore, the
      dephosphorylation of PKB, which in turn reduces the stimulation of glycogen
      synthesis.

PMID- 11574401
TI  - Inhibition of cytokine-induced NF-kappaB activation by adenovirus-mediated
      expression of a NF-kappaB super-repressor prevents beta-cell apoptosis.
AB  - Cytokine-induced beta-cell death is an important event in the pathogenesis of
      type 1 diabetes. The transcription factor nuclear factor-kappaB (NF-kappaB) is
      activated by interleukin-1beta (IL-1beta), and its activity promotes the
      expression of several beta-cell genes, including pro- and anti-apoptotic genes.
      To elucidate the role of cytokine (IL-1beta + gamma-interferon [IFN-gamma])
      induced expression of NF-kappaB in beta-cell apoptosis, rat beta-cells were
      infected with the recombinant adenovirus AdIkappaB((SA)2), which contained a
      nondegradable mutant form of inhibitory kappaB (IkappaB((SA)2), with S32A and
      S36A) that locks NF-kappaB in a cytosolic protein complex, preventing its nuclear
      action. Expression of IkappaB((SA)2) inhibited cytokine-stimulated nuclear
      translocation and DNA-binding of NF-kappaB. Cytokine-induced gene expression of
      several NF-kappaB targets, namely inducible nitric oxide synthase, Fas, and
      manganese superoxide dismutase, was prevented by AdIkappaB((SA)2), as established
      by reverse transcriptase-polymerase chain reaction, protein blot, and measurement
      of nitrite in the medium. Finally, beta-cell survival after IL-1beta + IFN-gamma
      treatment was significantly improved by IkappaB((SA)2) expression, mostly through
      inhibition of the apoptotic pathway. Based on these findings, we conclude that NF
      kappaB activation, under in vitro conditions, has primarily a pro-apoptotic
      function in beta-cells.

PMID- 11574402
TI  - The expression of hormone-sensitive lipase in clonal beta-cells and rat islets is
      induced by long-term exposure to high glucose.
AB  - Hormone-sensitive lipase (HSL) is expressed and enzymatically active in beta
      cells and has been proposed to be involved in the generation of the lipid-derived
      signal that seems to be necessary for glucose-stimulated insulin secretion. In
      this study, we investigated whether the expression of HSL in INS-1 cells and in
      rat islets is affected by exposure to high glucose concentrations. Incubation of
      INS-1 cells in 25 mmol/l glucose for 16 and 32 h induced HSL protein expression
      twofold, whereas no effect was observed after 4 and 8 h of incubation. The HSL
      activity, defined as the diglyceride lipase activity inhibited by anti-rat HSL
      antibodies, constituted approximately 25% of total diglyceride lipase activity
      and was induced to a similar extent as HSL protein levels. The glucose effect at
      16 h on HSL protein expression level was confirmed in freshly isolated rat
      islets. Exposure of INS-1 cells to different glucose concentrations for 16 h
      showed that the inductive effect on HSL protein levels was maximum at 20 mmol/l
      glucose (2- to 2.5-fold). Northern blot analysis demonstrated a more than
      threefold elevation of HSL mRNA levels. The induction was blocked by actinomycin
      D, and the half-life of the transcript seemed to be unchanged by high glucose,
      suggesting a transcriptional nature of the glucose effect on HSL gene expression.
      The nonmetabolizable glucose analog 2-deoxyglucose, which has no mitogenic
      effect, induced HSL approximately 1.3-fold, whereas mannose was similar to
      glucose, stimulating HSL expression 1.7- to 2-fold. The results suggest that HSL
      is involved in the beta-cell responses to hyperglycemia and also in generating
      the lipid signal that is needed in stimulus-secretion coupling.

PMID- 11574403
TI  - Noninvasive in vivo measurement of beta-cell mass in mouse model of diabetes.
AB  - Pancreatic beta-cell mass (BCM) is a major determinant of the quantity of insulin
      that can be secreted. BCM is markedly reduced in type 1 diabetes because of
      selective autoimmune destruction of beta-cells. Accurate assessment of BCM in
      human diabetes is limited to autopsy studies, which usually suffer from
      inadequate clinical information; thus, the development of noninvasive means of
      BCM measurement could be important in intervention therapy. The goal of this
      study was to develop such noninvasive methods for measuring BCM featuring target
      specific imaging probes and to investigate whether this technique is feasible,
      accurate, and predictive of BCM in normal and diabetic states. Using a beta-cell
      specific monoclonal antibody IC2, modified with a radioisotope chelator for
      nuclear imaging, we showed that highly specific binding and accumulation to beta
      cells occurs after intravenous administration of the probe, with virtually no
      binding to exocrine pancreas or stromal tissues. Furthermore, we observed a
      direct correlation between accumulation of the probe with BCM in diabetic and
      normal animals. Nuclear imaging of the animals that received an injection of the
      radioactive probe showed major difference in signal intensity between normal and
      diabetic pancreases. The results from this study set the route for further
      development of imaging probes for measuring BCM that would aid in diagnosis and
      treatment of diabetic patients in the clinic.

PMID- 11574404
TI  - Protein kinase Czeta activation mediates glucagon-like peptide-1-induced
      pancreatic beta-cell proliferation.
AB  - Glucagon-like peptide-1 (GLP-1), an insulinotropic and glucoincretin hormone, is
      a potentially important therapeutic agent in the treatment of diabetes. We
      previously provided evidence that GLP-1 induces pancreatic beta-cell growth
      nonadditively with glucose in a phosphatidylinositol-3 kinase (PI-3K)-dependent
      manner. In the present study, we investigated the downstream effectors of PI-3K
      to determine the precise signal transduction pathways that mediate the action of
      GLP-1 on beta-cell proliferation. GLP-1 increased extracellular signal-related
      kinase 1/2, p38 mitogen-activated protein kinase (MAPK), and protein kinase B
      activities nonadditively with glucose in pancreatic beta(INS 832/13) cells. GLP-1
      also caused nuclear translocation of the atypical protein kinase C (aPKC) zeta
      isoform in INS as well as in dissociated normal rat beta-cells as shown by
      immunolocalization and Western immunoblotting analysis. Tritiated thymidine
      incorporation measurements showed that the p38 MAPK inhibitor SB203580 suppressed
      GLP-1-induced beta-cell proliferation. Further investigation was performed using
      isoform-specific pseudosubstrates of classical (alpha, beta, and gamma) or zeta
      aPKC isoforms. The PKCzeta pseudosubstrate suppressed the proliferative action of
      GLP-1, whereas the inhibitor of classical PKC isoforms had no effect.
      Overexpression of a kinase-dead PKCzeta acting as a dominant negative protein
      suppressed GLP-1-induced proliferation. In addition, ectopic expression of a
      constitutively active PKCzeta mutant stimulated tritiated thymidine incorporation
      to the same extent as GLP-1, and the glucoincretin had no growth-promoting action
      under this condition. The data indicate that GLP-1-induced activation of PKCzeta
      is implicated in the beta-cell proliferative signal of the insulinotropic
      hormone. The results are consistent with a model in which GLP-1-induced PI-3K
      activation results in PKCzeta translocation to the nucleus, which may play a role
      in the pleiotropic effects (DNA synthesis, metabolic enzymes, and insulin gene
      expression) of the glucoincretin.

PMID- 11574405
TI  - Phosphorylation-dependent nucleocytoplasmic shuttling of pancreatic duodenal
      homeobox-1.
AB  - Pancreatic duodenal homeobox-1 (PDX-1) is a homeodomain protein that plays an
      important role in the development of the pancreas and in maintaining the identity
      and function of the islets of Langerhans. It also regulates the expression of the
      insulin gene in response to changes in glucose and insulin concentrations.
      Glucose and insulin regulate PDX-1 by way of a signaling pathway involving
      phosphatidylinositol 3-kinase (PI 3-kinase) and SAPK2/p38. Activation of this
      pathway leads to phosphorylation of PDX-1 and its movement into the nucleus. To
      investigate the intracellular trafficking of PDX-1, immunocytochemistry was used
      to localize PDX-1 in the human beta-cell line NesPDX-1, in which PDX-1 is
      overexpressed, and in MIN6 beta-cells. In low-glucose conditions, PDX-1 localized
      predominantly to the nuclear periphery, with some staining in the cytoplasm.
      After stimulation with glucose, PDX-1 was present in the nucleoplasm. The
      translocation of PDX-1 to the nucleoplasm was complete within 15 min and occurred
      in 5-10 mmol/l glucose. Insulin and sodium arsenite, an activator of the stress
      activated pathway, also stimulated PDX-1 movement from the nuclear periphery to
      the nucleoplasm. When cells were transferred between high glucose- and low
      glucose-containing medium, PDX-1 rapidly shuttled between the nuclear periphery
      and the nucleoplasm. Glucose- and insulin-stimulated translocation of PDX-1 to
      the nucleoplasm was inhibited by wortmannin and SB 203580, indicating that a
      pathway involving PI 3-kinase and SAPK2/p38 was involved; translocation was
      unaffected by PD 098959 and rapamycin, suggesting that neither mitogen-activated
      protein kinase nor p70(s6k) were involved. Arsenite-stimulated import of PDX-1
      into the nucleus was inhibited by SB 203580 but not by wortmannin. Export from
      the nucleoplasm to the nuclear periphery was inhibited by calyculin A and okadaic
      acid, suggesting that dephosphorylation of PDX-1 was involved. These results
      demonstrated that PDX-1 shuttles between the nuclear periphery and nucleoplasm in
      response to changes in glucose and insulin concentrations and that these events
      are dependent on PI 3-kinase, SAPK2/p38, and a nuclear phosphatase(s).

PMID- 11574406
TI  - Structural basis for the interference between nicorandil and sulfonylurea action.
AB  - Nicorandil is a new antianginal agent that potentially may be used to treat the
      cardiovascular side effects of diabetes. It is both a nitric oxide donor and an
      opener of ATP-sensitive K(+) (K(ATP)) channels in muscle and thereby causes
      vasodilation of the coronary vasculature. The aim of this study was to
      investigate the domains of the K(ATP) channel involved in nicorandil activity and
      to determine whether nicorandil interacts with hypoglycemic sulfonylureas that
      target K(ATP) channels in pancreatic beta-cells. K(ATP) channels in muscle and
      beta-cells share a common pore-forming subunit, Kir6.2, but possess alternative
      sulfonylurea receptors (SURs; SUR1 in beta-cells, SUR2A in cardiac muscle, and
      SUR2B in smooth muscle). We expressed recombinant K(ATP) channels in Xenopus
      oocytes and measured the effects of drugs and nucleotides by recording
      macroscopic currents in excised membrane patches. Nicorandil activated
      Kir6.2/SUR2A and Kir6.2/SUR2B but not Kir6.2/SUR1 currents, consistent with its
      specificity for cardiac and smooth muscle K(ATP) channels. Drug activity depended
      on the presence of intracellular nucleotides and was impaired when the Walker A
      lysine residues were mutated in either nucleotide-binding domain of SUR2.
      Chimeric studies showed that the COOH-terminal group of transmembrane helices
      (TMs), especially TM 17, is responsible for the specificity of nicorandil for
      channels containing SUR2. The splice variation between SUR2A and SUR2B altered
      the off-rate of the nicorandil response. Finally, we showed that nicorandil
      activity was unaffected by gliclazide, which specifically blocks SUR1-type K(ATP)
      channels, but was severely impaired by glibenclamide and glimepiride, which
      target both SUR1 and SUR2-type K(ATP) channels.

PMID- 11574407
TI  - Inducible and reversible beta-cell autoimmunity and hyperplasia in transgenic
      mice expressing a conditional oncogene.
AB  - Expression of the SV40 T antigen (Tag) in pancreatic beta-cells in transgenic
      mice has been shown to induce beta-cell tumorigenesis. We generated transgenic
      mice in which Tag expression is inducible and reversible by the tet-on gene
      regulation system. These mice develop beta-cell tumors only when treated with the
      inducer doxycycline (dox). Tag expression in vivo is reversible upon dox
      withdrawal. As a result, beta-cell proliferation is greatly reduced, indicating
      that genetic changes, which may occur in the transformed cells, do not allow Tag
      independent proliferation. Induction of Tag expression after immune recognition
      of self-antigens has been established triggers an autoimmune response against
      beta-cells, as evidenced by insulitis. Shut-off of Tag expression results in
      elimination of insulitis, suggesting that this process depends on continuous
      expression of the target antigen. In addition, the reversibility of autoimmunity
      suggests that beta-cell damage caused by the anti-Tag immune response does not
      elicit secondary responses to other newly exposed beta-cell antigens, which would
      have persisted after Tag elimination. beta-Cell proliferation in this model is
      accompanied by cell apoptosis. Apoptosis persisted for several weeks in the
      islets after dox removal. In close to 40% of the mice analyzed, this process
      reduced the islet size back to normal, suggesting the existence of a homeostatic
      mechanism that maintains beta-cell mass within the normal range.

PMID- 11574408
TI  - Effects of leptin deficiency and short-term repletion on hepatic gene expression
      in genetically obese mice.
AB  - By supplying most organs of the body with metabolic substrates, the liver plays a
      central role in maintaining energy balance. Hepatic metabolism of glucose, fatty
      acids, and lipoproteins is disrupted in the leptin-deficient obese
      (Lep(ob)/Lep(ob)) mouse, leading to hyperglycemia, steatosis, and
      hypercholesterolemia. Microarray expression profiles were used to identify
      transcriptional perturbations that underlie the altered hepatic physiology of
      Lep(ob)/Lep(ob) mice. A wide variety of genes involved in fatty acid metabolism
      are altered in expression, which suggests that both fatty acid synthesis and
      oxidation programs are activated in obese mice. The expression of a small subset
      of genes is upregulated by leptin deficiency, not modulated by caloric
      restriction, and markedly suppressed by short-term leptin treatment. Among these
      leptin-regulated genes, apolipoprotein A-IV is a strong candidate for mediating
      the atherogenic-resistant phenotype of Lep(ob)/Lep(ob) mice.

PMID- 11574409
TI  - Intrauterine growth retardation leads to the development of type 2 diabetes in
      the rat.
AB  - Intrauterine growth retardation has been linked to the development of type 2
      diabetes in later life. The mechanisms underlying this phenomenon are unknown. We
      have developed a model of uteroplacental insufficiency, a common cause of
      intrauterine growth retardation, in the rat. Bilateral uterine artery ligation
      was performed on day 19 of gestation (term is 22 days) in the pregnant rat; sham
      operated pregnant rats served as controls. Birth weights of intrauterine growth
      retarded (IUGR) animals were significantly lower than those of controls until
      approximately 7 weeks of age, when IUGR rats caught up to controls. Between 7 and
      10 weeks of age, the growth of IUGR rats accelerated and surpassed that of
      controls, and by 26 weeks of age, IUGR rats were obese (P < 0.05 vs. controls).
      No significant differences were observed in blood glucose and plasma insulin
      levels at 1 week of age. However, between 7 and 10 weeks of age, IUGR rats
      developed mild fasting hyperglycemia and hyperinsulinemia (P < 0.05 vs.
      controls). At age 26 weeks, IUGR animals had markedly elevated levels of glucose
      (P < 0.05 vs. controls). IUGR animals were glucose-intolerant and insulin
      resistant at an early age. First-phase insulin secretion in response to glucose
      was also impaired early in life in IUGR rats, before the onset of hyperglycemia.
      There were no significant differences in beta-cell mass, islet size, or
      pancreatic weight between IUGR and control animals at 1 and 7 weeks of age.
      However, in 15-week-old IUGR rats, the relative beta-cell mass was 50% that of
      controls, and by 26 weeks of age, beta-cell mass was less than one-third that of
      controls (P < 0.05). The data presented here support the hypothesis that an
      abnormal intrauterine milieu can induce permanent changes in glucose homeostasis
      after birth and lead to type 2 diabetes in adulthood.

PMID- 11574410
TI  - Phenotypic correction of diabetic mice by adenovirus-mediated glucokinase
      expression.
AB  - Hyperglycemia of diabetes is caused in part by perturbation of hepatic glucose
      metabolism. Hepatic glucokinase (GK) is an important regulator of glucose storage
      and disposal in the liver. GK levels are lowered in patients with maturity-onset
      diabetes of the young and in some diabetic animal models. Here, we explored the
      adenoviral vector-mediated overexpression of GK in a diet-induced murine model of
      type 2 diabetes as a treatment for diabetes. Diabetic mice were treated by
      intravenous administration with an E1/E2a/E3-deleted adenoviral vector encoding
      human hepatic GK (Av3hGK). Two weeks posttreatment, the Av3hGK-treated diabetic
      mice displayed normalized fasting blood glucose levels (95 +/- 4.8 mg/dl; P <
      0.001) when compared with Av3Null (135 +/- 5.9 mg/dl), an analogous vector
      lacking a transgene, and vehicle-treated diabetic mice (134 +/- 8 mg/dl). GK
      treatment also resulted in lowered insulin levels (632 +/- 399 pg/ml; P < 0.01)
      compared with the control groups (Av3Null, 1,803 +/- 291 pg/ml; vehicle, 1,861 +/
      392 pg/ml), and the glucose tolerance of the Av3hGK-treated diabetic mice was
      normalized. No significant increase in plasma or hepatic triglycerides, or plasma
      free fatty acids was observed in the Av3hGK-treated mice. These data suggest that
      overexpression of GK may have a therapeutic potential for the treatment of type 2
      diabetes.

PMID- 11574411
TI  - Troglitazone not only increases GLUT4 but also induces its translocation in rat
      adipocytes.
AB  - Thiazolidinediones, insulin-sensitizing agents, have been reported to increase
      glucose uptake along with the expression of glucose transporters in adipocytes
      and cardiomyocytes. Recently, we have further suggested that the translocation of
      GLUT4 is stimulated by thiazolidinediones in L6 myocytes. However, the direct
      effects of thiazolidinediones on translocation of glucose transporters have not
      yet been determined. In this study, using hemagglutinin epitope-tagged GLUT4
      (GLUT4-HA), we provide direct evidence of the effect of troglitazone on the
      translocation of GLUT4 in rat epididymal adipocytes. Primary cultures of rat
      adipocytes were transiently transfected with GLUT4-HA and overexpressed eightfold
      compared with endogenous GLUT4 in transfected cells. A total of 24 h of treatment
      with troglitazone (10(-4) mol/l) increased the cell surface level of GLUT4-HA by
      1.5 +/- 0.03-fold (P < 0.01) without changing the total amount of GLUT4-HA,
      whereas it increased the protein level of endogenous GLUT4 (1.4-fold) without
      changing that of GLUT1. Thus, the direct effect on the translocation can be
      detected apart from the increase in endogenous GLUT4 content using GLUT4-HA.
      Troglitazone not only increased the translocation of GLUT4-HA on the cell surface
      in the basal state but also caused a leftward shift in the dose-response
      relations between GLUT4-HA translocation and insulin concentration in the medium
      (ED(50): from approximately 0.1 to 0.03 nmol/l). These effects may partly
      contribute to the antidiabetic activity of troglitazone in patients with obesity
      and type 2 diabetes.

PMID- 11574412
TI  - Pharmacological antilipolysis restores insulin sensitivity during growth hormone
      exposure.
AB  - Stimulation of lipolysis and the induction of resistance to insulin's actions on
      glucose metabolism are well-recognized effects of growth hormone (GH). To
      evaluate whether these two features are causally linked, we studied the impact of
      pharmacologically induced antilipolysis in seven GH-deficient patients (mean [+/-
      SE] age 37 +/- 4 years). Each subject was studied under four different
      conditions: during continuation of GH replacement alone (A), after
      discontinuation of GH replacement for 2 days (B), after GH replacement and short
      term coadministration of acipimox (250 mg, p.o., b.i.d., for 2 days) (C), and
      after administration of acipimox alone (D). At the end of each study, total and
      regional substrate metabolisms were assessed in the basal state and after a 3-h
      hyperinsulinemic/euglycemic clamp. Serum levels of free fatty acids (FFAs) were
      elevated with GH alone (A) and suppressed with acipimox (C and D). Basal rates of
      lipid oxidation were highest with GH alone (A), and suppressed by 50% with
      acipimox (B versus D, P < 0.01; A versus C, P < 0.05). Basal glucose oxidation
      rates were lowest with GH alone (A) and highest with acipimox (C and D) (P =
      0.01). Insulin-stimulated rates of total glucose turnover were significantly
      lower with GH alone as compared with all other conditions (P = 0.004). Insulin
      sensitivity as assessed by the M value (rate of glucose infusion) was reduced
      with GH alone as compared with all other conditions (M value in mg. kg(-1). min(
      1): GH alone [A], 2.55 +/- 0.64; discontinuation of GH [B], 4.01 +/- 0.70; GH
      plus acipimox [C], 3.96 +/- 1.34; acipimox alone [D], 4.96 +/- 0.91; P < 0.01).
      During pharmacological antilipolysis, GH did not significantly influence insulin
      sensitivity (C versus D; P = 0.19). From our results, we reached the following
      conclusions: 1) Our data strongly suggest that the insulin antagonistic actions
      of GH on glucose metabolism are causally linked to the concomitant activation of
      lipolysis. 2) In addition, GH may induce residual insulin resistance through non
      FFA-dependent mechanisms. 3) The cellular and molecular mechanisms subserving the
      insulin antagonistic effects of GH remain to be elucidated.

PMID- 11574413
TI  - Direct thiazolidinedione action on isolated rat skeletal muscle fuel handling is
      independent of peroxisome proliferator-activated receptor-gamma-mediated changes
      in gene expression.
AB  - Thiazolidinediones (TZDs) are believed to induce insulin sensitization by
      modulating gene expression via agonistic stimulation of the nuclear peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma). We have shown earlier that
      the TZD troglitazone inhibits mitochondrial fuel oxidation in isolated rat
      skeletal muscle. In the present study, rat soleus muscle strips were exposed to
      TZDs to examine whether the inhibition of fuel oxidation is mediated by PPAR
      gamma activation. Our findings consistently indicated direct, acute, and PPAR
      gamma-independent TZD action on skeletal muscle fuel metabolism. Rapid
      stimulation of lactate release by 20 micromol/l troglitazone within 30 min
      suggested that direct TZD action on skeletal muscle in vitro does not rely on
      changes in gene expression rates (12.6 +/- 0.6 [control] vs. 16.0 +/- 0.8
      micromol. g(-1). h(-1) [troglitazone]; P < 0.01). This conclusion was supported
      by the failure of actinomycin D and cycloheximide to block the effects of
      troglitazone. Mitochondrial fuel oxidation was consistently inhibited by six
      different TZDs (percent inhibition of CO(2) production from palmitate after 25 h:
      troglitazone, -61 +/- 2%; pioglitazone, -43 +/- 7%; rosiglitazone, -22 +/- 6%;
      BM13.1258, -47 +/- 9%; BM15.2054, -51 +/- 4%; and T-174, -59 +/- 4% [P < 0.005
      each]), but not by PPAR-gamma agonistic compounds not belonging to the TZD class
      (JTT-501, -5 +/- 7% [NS]; prostaglandin J(2), 17 +/- 7% [P < 0.05]), which
      further argues against dependence on PPAR-gamma activation. In summary, our
      findings provided good evidence that direct inhibition of mitochondrial fuel
      oxidation in isolated skeletal muscle is a group-specific effect of TZDs and is
      independent of PPAR-gamma-mediated gene expression.

PMID- 11574414
TI  - Thiazolidinedione treatment prevents free fatty acid-induced insulin resistance
      in male wistar rats.
AB  - We sought to ascertain whether pretreatment with troglitazone (20 days) could
      prevent acute free fatty acid (FFA)-induced insulin resistance in male Wistar
      rats. Animals were divided into three groups: 1) control, 2) FFA infusion alone
      (FFA1), and 3) thiazolidinedione (TZD)-treated + FFA infusion (FFA1). Days before
      a hyperinsulinemic-euglycemic clamp, all animals were cannulated in the jugular
      vein (infusion) and carotid artery (sampling). Animals were allowed 5 days to
      recover from surgery and fasted 12 h before the experiment. Glucose (variable),
      insulin (40 mU. kg(-1). min(-1)), and Liposyn (heparinized 10% lipid emulsion)
      infusions were initiated simultaneously and continued from 0-120 min. Steady
      state glucose, 8.3 +/- 0.14 mmol/l, and insulin concentrations, 7.3 +/- 2.45
      nmol/l, were the same between groups. Interestingly, steady-state FFA levels were
      significantly lower in animals pretreated with TZD compared with FFA alone (1.83
      +/- 0.26 vs. 2.96 +/- 0.25 mmol/l; P = 0.009), despite matched intralipid
      infusion rates. A second group of TZD-treated animals (TZD + FFA2) were infused
      with intralipid at a higher infusion rate (44%) to match the arterial
      concentrations of FFA1. The glucose infusion and insulin-stimulated glucose
      disposal rates (GDRs) were significantly decreased (40%) for untreated Liposyn
      infused (FFA1) compared with control rats. In addition, insulin receptor
      substrate-1 (IRS-1) phosphorylation and IRS-1-associated phosphatidylinositol
      (PI) 3-kinase activity was significantly reduced, 30-50%, in FFA1 rats. TZD
      pretreatment prevented the FFA-induced decrement in insulin signaling. Fatty acid
      translocase (FAT/CD36) also was significantly reduced (56%) in untreated FFA1
      rats after the clamp but remained identical to control values for TZD-treated
      rats. In conclusion, acutely elevated FFA levels 1) induced a significant
      reduction in tracer-determined GDR paralleled by impaired tyrosine
      phosphorylation of IRS-1 and reduced IRS-1-associated PI 3-kinase activity and 2)
      induced a significant reduction in FAT/CD36 total protein. TZD pretreatment
      prevented FFA-induced decrements in insulin action and prevented the reduction in
      FAT/CD36 protein.

PMID- 11574415
TI  - Small molecule insulin receptor activators potentiate insulin action in insulin
      resistant cells.
AB  - In type 2 diabetes, impaired insulin signaling leads to hyperglycemia and other
      metabolic abnormalities. To study a new class of antidiabetic agents, we compared
      two small, nonpeptide molecules that activate insulin receptor (IR) beta-subunit
      tyrosine kinase activity: Merck L7, a direct IR agonist, and Telik's TLK16998, an
      IR sensitizer. In rat hepatoma cells (HTCs) that overexpress the IR (HTC-IR), IR
      autophosphorylation was directly activated by L7 in the absence of insulin.
      TLK16998 did not directly activate IR autophosphorylation, but it enhanced IR
      autophosphorylation in the presence of insulin. Tyrosine phosphorylation of an
      endogenous 185-kDa IR substrate was also significantly enhanced by both Merck L7
      alone and TLK16998 plus insulin. Adding TLK16998 to L7 produced synergistic
      effects, further indicating that these two compounds act on the IR through
      separate mechanisms. We next studied HTC-IR(Delta485-599) cells, which
      overexpress a mutant IR with a deletion in the alpha-subunit connecting domain
      that does not undergo autophosphorylation in response to insulin binding. L7 was
      able to directly activate autophosphorylation of the deletion mutant IR in these
      cells, whereas TLK16998 had no effect. Compounds were then tested in three other
      cell models of impaired IR function. Both TLK16998 and Merck L7 improved IR
      autophosphorylation in cells with diminished IR signaling due to either treatment
      with tumor necrosis factor-alpha or overexpression of membrane glycoprotein PC-1.
      However, in TPA (tetradecanoylphorbol acetate)-treated cells, TLK16998 but not
      Merck L7 was able to significantly reverse the impaired insulin-stimulated IR
      autophosphorylation. In summary, these two classes of IR activators selectively
      increased IR function in a variety of insulin-resistant cell lines.

PMID- 11574416
TI  - Changes in regional brain (18)F-fluorodeoxyglucose uptake at hypoglycemia in type
      1 diabetic men associated with hypoglycemia unawareness and counter-regulatory
      failure.
AB  - We examined the effects of acute moderate hypoglycemia and the condition of
      hypoglycemia unawareness on regional brain uptake of the labeled glucose analog
      [(18)F]fluorodeoxyglucose (FDG) using positron emission tomography (PET). FDG-PET
      was performed in diabetic patients with (n = 6) and without (n = 7) hypoglycemia
      awareness. Each patient was studied at plasma glucose levels of 5 and 2.6 mmol/l,
      applied by glucose clamp techniques, in random order. Hypoglycemia-unaware
      patients were asymptomatic during hypoglycemia, with marked attenuation of their
      epinephrine responses (mean [+/- SD] peak of 0.77 +/- 0.39 vs. 7.52 +/- 2.9
      nmol/l; P < 0.0003) and a reduced global brain FDG uptake ([mean +/- SE] 2.592 +/
      0.188 vs. 2.018 +/- 0.174 at euglycemia; P = 0.027). Using statistical
      parametric mapping (SPM) to analyze images of FDG uptake, we identified a
      subthalamic brain region that exhibited significantly different behavior between
      the aware and unaware groups. In the aware group, there was little change in the
      normalized FDG uptake in this region in response to hypoglycemia ([mean +/- SE]
      0.654 +/- 0.016 to 0.636 +/- 0.013; NS); however, in the unaware group, the
      uptake in this region fell from 0.715 +/- 0.015 to 0.623 +/- 0.012 (P = 0.001).
      Our data were consistent with the human hypoglycemia sensor being anatomically
      located in this brain region, and demonstrated for the first time a change in its
      metabolic function associated with the failure to trigger a counter-regulatory
      response.

PMID- 11574417
TI  - Intramyocellular lipid is associated with resistance to in vivo insulin actions
      on glucose uptake, antilipolysis, and early insulin signaling pathways in human
      skeletal muscle.
AB  - To examine whether and how intramyocellular lipid (IMCL) content contributes to
      interindividual variation in insulin action, we studied 20 healthy men with no
      family history of type 2 diabetes. IMCL was measured as the resonance of
      intramyocellular CH(2) protons in lipids/resonance of CH(3) protons of total
      creatine (IMCL/Cr(T)), using proton magnetic resonance spectroscopy in vastus
      lateralis muscle. Whole-body insulin sensitivity was measured using a 120-min
      euglycemic-hyperinsulinemic (insulin infusion rate 40 mU/m(2). min) clamp. Muscle
      biopsies of the vastus lateralis muscle were taken before and 30 min after
      initiation of the insulin infusion to assess insulin signaling. The subjects were
      divided into groups with high IMCL (HiIMCL; 9.5 +/- 0.9 IMCL/Cr(T), n = 10) and
      low IMCL (LoIMCL; 3.0 +/- 0.5 IMCL/Cr(T), n = 10), the cut point being median
      IMCL (6.1 IMCL/Cr(T)). The groups were comparable with respect to age (43 +/- 3
      vs. 40 +/- 3 years, NS, HiIMCL versus LoIMCL), BMI (26 +/- 1 vs. 26 +/- 1
      kg/m(2), NS), and maximal oxygen consumption (33 +/- 2 vs. 36 +/- 3 ml. kg(-1).
      min(-1), NS). Whole-body insulin-stimulated glucose uptake was lower in the
      HiIMCL group (3.0 +/- 0.4 mg. kg(-1). min(-1)) than the LoIMCL group (5.1 +/- 0.5
      mg. kg(-1). min(-1), P < 0.05). Serum free fatty acid concentrations were
      comparable basally, but during hyperinsulinemia, they were 35% higher in the
      HiIMCL group than the LoIMCL group (P < 0.01). Study of insulin signaling
      indicated that insulin-induced tyrosine phosphorylation of the insulin receptor
      (IR) was blunted in HiIMCL compared with LoIMCL (57 vs. 142% above basal, P <
      0.05), while protein expression of the IR was unaltered. IR substrate-1
      associated phosphatidylinositol (PI) 3-kinase activation by insulin was also
      lower in the HiIMCL group than in the LoIMCL group (49 +/- 23 vs. 84 +/- 27%
      above basal, P < 0.05 between HiIMCL and LoIMCL). In conclusion, IMCL
      accumulation is associated with whole-body insulin resistance and with defective
      insulin signaling in skeletal muscle independent of body weight and physical
      fitness.

PMID- 11574418
TI  - Increased lactate release per fat cell in normoglycemic first-degree relatives of
      individuals with type 2 diabetes.
AB  - The aim of this study was to examine subcutaneous lactate production in the
      relatives of individuals with type 2 diabetes. Therefore, we recruited seven
      healthy first-degree relatives of type 2 diabetic patients and seven pairwise,
      matched, healthy control subjects without any heredity for diabetes. All subjects
      were studied with a euglycemic insulin clamp at approximately 600 pmol/l,
      abdominal subcutaneous microdialysis, and (133)Xe clearance. Furthermore, a
      subcutaneous needle biopsy was performed to determine fat cell size. In the
      fasting state, interstitial lactate was 40% higher in relatives than in control
      subjects (P = 0.043), but net lactate production was similar in both groups.
      However, during the insulin clamp, interstitial lactate (2.50 +/- 0.29 vs. 1.98
      +/- 0.26 mmol/l, P = 0.018), interstitial-arterial lactate concentration
      difference (1.08 +/- 0.30 vs. 0.53 +/- 0.24 mmol/l, P = 0.028), and net lactate
      release per fat cell (10.9 +/- 3.7 vs. 2.8 +/- 1.3 fmol. cell(-1). min(-1), P =
      0.018) were increased in the relatives. We conclude that first-degree relatives
      of type 2 diabetic patients may have an enhanced net lactate release per fat cell
      in abdominal subcutaneous tissue. This could suggest a pathological regulation in
      adipose tissue that is of importance for the metabolic defects known in type 2
      diabetic relatives.

PMID- 11574419
TI  - Caffeine ingestion decreases glucose disposal during a hyperinsulinemic
      euglycemic clamp in sedentary humans.
AB  - The purpose of this investigation was to examine the effect of caffeine (an
      adenosine receptor antagonist) on whole-body insulin-mediated glucose disposal in
      resting humans. We hypothesized that glucose disposal would be lower after the
      administration of caffeine compared with placebo. Healthy, lean, sedentary (n =
      9) men underwent two trial sessions, one after caffeine administration (5 mg/kg
      body wt) and one after placebo administration (dextrose) in a double-blind
      randomized design. Glucose disposal was assessed using a hyperinsulinemic
      euglycemic clamp. Before the clamp, there were no differences in circulating
      levels of methylxanthines, catecholamines, or glucose. Euglycemia was maintained
      throughout the clamp with no difference in plasma glucose concentrations between
      trials. The insulin concentrations were also similar in the caffeine and placebo
      trials. After caffeine administration, glucose disposal was 6.38 +/- 0.76 mg/kg
      body wt compared with 8.42 +/- 0.63 mg/kg body wt after the placebo trial. This
      represents a significant (P < 0.05) decrease (24%) in glucose disposal after
      caffeine ingestion. In addition, carbohydrate storage was 35% lower (P < 0.05) in
      the caffeine trial than in the placebo trial. Furthermore, even when the
      difference in glucose disposal was normalized between the trials, there was a 23%
      difference in the amount of carbohydrate stored after caffeine administration
      compared with placebo administration. Caffeine ingestion also resulted in higher
      plasma epinephrine levels than placebo ingestion (P < 0.05). These data support
      our hypothesis that caffeine ingestion decreases glucose disposal and suggests
      that adenosine plays a role in regulating glucose disposal in resting humans.

PMID- 11574420
TI  - Hexosamine-induced fibronectin protein synthesis in mesangial cells is associated
      with increases in cAMP responsive element binding (CREB) phosphorylation and
      nuclear CREB: the involvement of protein kinases A and C.
AB  - Hyperglycemia-induced alterations in mesangial (MES) cell function and
      extracellular matrix protein accumulation are seen in diabetic glomerulopathy.
      Recent studies have demonstrated that some of the effects of high glucose (HG) on
      cellular metabolism are mediated by the hexosamine biosynthesis pathway (HBP), in
      which fructose-6-phosphate is converted to glucosamine 6-phosphate by the rate
      liming enzyme glutamine:fructose-6-phosphate amidotransferase (GFA). In this
      study, we investigated the role of HBP on HG-stimulated fibronectin protein
      synthesis, a matrix component, in SV-40-transformed rat kidney MES cells.
      Treatment of MES cells with 25 mmol/l glucose (HG) for 48 h increases cellular
      fibronectin levels by two- to threefold on Western blots when compared with low
      glucose (5 mmol/l). Glucosamine (GlcN; 1.5 mmol/l), which enters the hexosamine
      pathway distal to GFA action, also increases fibronectin synthesis. Azaserine
      (AZA; 0.5 micromol/l), an inhibitor of GFA, blocks the HG- but not the GlcN
      induced fibronectin synthesis. Fibronectin contains cAMP responsive element (CRE)
      consensus sequences in its promoter and the phosphorylation of CRE-binding
      protein (CREB) may regulate its expression. On Western blots, HG and GlcN
      stimulate two- to threefold the phosphorylation of CREB at Ser 133, whereas CREB
      protein content was unaltered by either HG or GlcN. In addition, nuclear CREB
      activity was increased by HG and GlcN on gel-shift assays using (32)P-CRE
      oligonucleotides. AZA impeded the HG-enhanced CREB phosphorylation and CRE
      binding but had no effect on GlcN-mediated CREB phosphorylation and CRE binding.
      Pharmacologic inhibition of protein kinase C (PKC) and protein kinase A (PKA),
      which are involved in hexosamine-mediated matrix production, blocked the CREB
      phosphorylation and fibronectin synthesis seen in HG and GlcN conditions. We
      conclude that the effects of HG on fibronectin synthesis in the mesangium are
      mediated by the HBP possibly via hexosamine regulation of CREB and PKC/PKA
      signaling pathways. These results support the hypothesis that the HBP is a sensor
      and regulator of the actions of glucose in the kidney.

PMID- 11574421
TI  - Hyperglycemia activates p53 and p53-regulated genes leading to myocyte cell
      death.
AB  - To determine whether enzymatic p53 glycosylation leads to angiotensin II
      formation followed by p53 phosphorylation, prolonged activation of the renin
      angiotensin system, and apoptosis, ventricular myocytes were exposed to levels of
      glucose mimicking diabetic hyperglycemia. At a high glucose concentration, O
      glycosylation of p53 occurred between 10 and 20 min, reached its peak at 1 h, and
      then decreased with time. Angiotensin II synthesis increased at 45 min and 1 h,
      resulting in p38 mitogen-activated protein (MAP) kinase-driven p53
      phosphorylation at Ser 390. p53 phosphorylation was absent at the early time
      points, becoming evident at 1 h, and increasing progressively from 3 h to 4 days.
      Phosphorylated p53 at Ser 18 and activated c-Jun NH(2)-terminal kinases were
      identified with hyperglycemia, whereas extracellular signal-regulated kinase was
      not phosphorylated. Upregulation of p53 was associated with an accumulation of
      angiotensinogen and AT(1) and enhanced production of angiotensin II. Bax quantity
      also increased. These multiple adaptations paralleled the concentrations of
      glucose in the medium and the duration of the culture. Myocyte death by apoptosis
      directly correlated with glucose and angiotensin II levels. Inhibition of O
      glycosylation prevented the initial synthesis of angiotensin II, p53, and p38-MAP
      kinase (MAPK) phosphorylation and apoptosis. AT(1) blockade had no influence on O
      glycosylation of p53, but it interfered with p53 phosphorylation; losartan also
      prevented phosphorylation of p38-MAPK by angiotensin II. Inhibition of p38-MAPK
      mimicked at a more distal level the consequences of losartan. In conclusion,
      these in vitro results support the notion that hyperglycemia with diabetes
      promotes myocyte apoptosis mediated by activation of p53 and effector responses
      involving the local renin-angiotensin system.

PMID- 11574422
TI  - High glucose-enhanced mesangial cell extracellular signal-regulated protein
      kinase activation and alpha1(IV) collagen expression in response to endothelin-1:
      role of specific protein kinase C isozymes.
AB  - High glucose (HG) stimulates glomerular mesangial cell (MC) expression of
      extracellular matrix, a process involving protein kinase C (PKC) isozymes and
      enhanced signaling by autocrine peptides such as endothelin-1 (ET-1). The purpose
      of this study was to identify the specific PKC isozymes mediating the effects of
      HG on MC extracellular signal-regulated protein kinase (ERK1/2) signaling and
      alpha1(IV) collagen expression in response to ET-1. HG (30 mmol/l for 72 h)
      enhanced ET-1-stimulated alpha1(IV) collagen mRNA expression from 1.2 +/- 0.1
      fold to 1.9 +/- 0.2-fold (P < 0.05 vs. normal glucose [NG] + ET-1), and the
      effect was significantly reduced by Calphostin C or the MEK (mitogen-activated
      protein kinase kinase) inhibitor PD98059. In transiently transfected MCs,
      dominant-negative (DN)-PKC-delta, -epsilon, or -zeta inhibited ET-1 activation of
      ERK1/2. Likewise, downstream of ERK1/2, ET-1 stimulated Elk-1-driven GAL4
      luciferase activity to 11 +/- 1-fold (P < 0.002 vs. NG + ET-1) in HG, and DN-PKC
      delta, -epsilon, or -zeta attenuated this response to NG levels. HG enhanced ET-1
      stimulated intracellular alpha1(IV) collagen protein expression, assessed by
      confocal immunofluorescence imaging, showed that individual DN-PKC-delta, 
      epsilon, -zeta, as well as DN-PKC-alpha and -beta, attenuated the response. Thus,
      HG-enhanced ET-1 stimulation of alpha1(IV) collagen expression requires PKC
      delta, -epsilon, and -zeta to act through an ERK1/2-dependent pathway and via PKC
      alpha and -beta, which are independent of ERK1/2.

PMID- 11574423
TI  - The relation of markers of inflammation to the development of glucose disorders
      in the elderly: the Cardiovascular Health Study.
AB  - Several studies suggest that inflammation plays a role in the pathogenesis of
      some glucose disorders in adults. We tested this hypothesis in a longitudinal
      cohort study of older individuals who had normal fasting glucose (FG) values at
      baseline. We compared the baseline levels of six inflammatory markers in
      participants who had developed glucose disorders at follow-up with those of
      participants whose FG remained normal at follow-up. Participants were members of
      the Cardiovascular Health Study, a prospective study of risk factors for
      cardiovascular disease in adults > or =65 years. All 5,888 participants had
      baseline testing, including FG and markers of inflammation: white blood cell and
      platelet counts and albumin, fibrinogen, C-reactive protein (CRP), and factor
      VIIIc levels. At 3-4 years of follow-up, 4,481 (84.5%) of those who were alive
      had FG levels retested. Participants who developed diabetes (n = 45) had higher
      median levels of CRP at baseline than those who remained normoglycemic. On
      multivariate analysis, those with elevated CRP levels (75th percentile [2.86
      mg/l] vs. 25th percentile [0.82 mg/l]) were 2.03 times (95% confidence intervals,
      1.44-2.86) more likely to have diabetes on follow-up. Adjustment for confounders
      and other inflammatory markers did not appreciably change this finding. There was
      no relationship between the development of diabetes and other markers of
      inflammation. Inflammation, as measured by CRP levels, is associated with the
      development of diabetes in the elderly. Understanding the role of inflammation in
      the pathogenesis of glucose disorders in this age-group may lead to better
      classification and treatment of glucose disorders among them.

PMID- 11574424
TI  - A prospective study of drinking patterns in relation to risk of type 2 diabetes
      among men.
AB  - Using data from a 12-year prospective study, we determined the importance of the
      pattern of alcohol consumption as a risk factor for type 2 diabetes in a cohort
      of 46,892 U.S. male health professionals who completed biennial postal
      questionnaires. Overall, 1,571 new cases of type 2 diabetes were documented.
      Compared with zero alcohol consumption, consumption of 15-29 g/day of alcohol was
      associated with a 36% lower risk of diabetes (RR = 0.64; 95% CI 0.53-0.77). This
      inverse association between moderate consumption and diabetes remained if light
      drinkers rather than abstainers were used as the reference group (RR = 0.60, CI
      0.50-0.73). There were few heavy drinkers, but the inverse association persisted
      to those drinking >/=50 g/day of alcohol (RR = 0.60, CI 0.43-0.84). Frequency of
      consumption was inversely associated with diabetes. Consumption of alcohol on at
      least 5 days/week provided the greatest protection, even when less than one drink
      per drinking day was consumed (RR = 0.48, CI 0.27-0.86). Compared with infrequent
      drinkers, for each additional day per week that alcohol was consumed, risk was
      reduced by 7% (95% CI 3-10%) after controlling for average daily consumption.
      There were similar and independent inverse associations for beer, liquor, and
      white wine. Our findings suggested that frequent alcohol consumption conveys the
      greatest protection against type 2 diabetes, even if the level of consumption per
      drinking day is low. Beverage choice did not alter risk.

PMID- 11574425
TI  - A major gene effect on fasting insulin and insulin sensitivity in familial
      combined hyperlipidemia.
AB  - The most common inherited dyslipidemia, familial combined hyperlipidemia (FCHL),
      is associated with insulin resistance. Whether insulin sensitivity in these
      families is inherited is not known. Therefore, we investigated the inheritance of
      insulin sensitivity in 352 nondiabetic family members from 37 families with FCHL,
      105 of whom had undergone testing using the hyperinsulinemic-euglycemic clamp
      technique for the measurement of insulin sensitivity. First, complex segregation
      analysis of fasting insulin levels (both unadjusted and age-, age(2)-, and BMI
      adjusted) was used for modeling of the variance in fasting insulin levels. In
      these analyses, Mendelian codominant inheritance (P = 0.320 for unadjusted and P
      = 0.295 for adjusted insulin values) was not rejected over the most general model
      and fit the data significantly better than the sporadic model (P < 0.001).
      Polygenic and environmental models were rejected (P < 0.001). The Mendelian
      codominant model explained 44 and 45% of the variance in unadjusted and adjusted
      fasting insulin levels, respectively. The proposed genotypes of this locus, based
      on segregation analysis, were associated with directly measured insulin
      sensitivity in 105 FCHL family members who underwent the hyperinsulinemic
      euglycemic clamp (P < 0.001). These results provide evidence for a major gene
      regulating insulin sensitivity in FCHL families. Possible pleiotropic effects of
      this insulin sensitivity locus on dyslipidemias in FCHL remain to be elucidated.

PMID- 11574426
TI  - Characterization of the annexin I gene and evaluation of its role in type 2
      diabetes.
AB  - In a previous study, we identified suggestive linkage between type 2 diabetes and
      a locus on chromosome 9p13-q21. This region contains the gene annexin I (ANXA1),
      encoding a protein suggested to be involved in both insulin secretion and insulin
      action. In this study, we sequenced the exon/intron boundaries of the human ANXA1
      gene and performed mutation screening in 41 individuals from the initial linkage
      study. We identified five single nucleotide polymorphisms A58G, A401G, intronic
      variance sequence (IVS)8-28A/G, IVS11 +31A/G, and IVS12-11T/G, which were further
      tested for association to diabetes in 197 parent/offspring trios using the
      transmission disequilibrium test. No significant association with type 2 diabetes
      was observed, although the common A allele of the +58A/G variant gave a 22:12
      transmission distortion (P = 0.12). This variant was further genotyped in 481
      case and control subjects, but no difference in allele, genotype, or haplotype
      frequencies were observed between the groups. Further, a novel polymorphic
      (CA)(15-25) repeat in intron 11 was genotyped in the subjects included in the
      initial linkage study. No improvement of the original finding was observed. We
      therefore concluded that the ANXA1 gene is unlikely to harbor variants that
      contribute to risk of type 2 diabetes.

PMID- 11574427
TI  - Analysis of the coding and promoter regions of the autoantigen IA-2 in subjects
      with and without autoantibodies to IA-2.
AB  - Despite extensive studies on HLA polymorphism, there have been few, if any,
      studies on allelic forms or mutations in proteins that serve as autoantigens. The
      present experiments were designed to look for alterations in the coding and
      promoter regions of the autoantigen IA-2 in type one (insulin-dependent) diabetic
      patients with autoantibodies to IA-2 as compared with siblings without diabetes
      or autoantibodies to IA-2. Genomic DNA was used as a template and was amplified
      by polymerase chain reaction, with pairs of primers encompassing the promoter
      region and the 23 exons of the coding region of IA-2. A total of nine nucleotide
      changes were found in the coding region of the six type 1 diabetic patients; four
      were silent and five were missense changes, but all occurred in the extracellular
      domain of IA-2 to which autoantibodies are not directed. Few, if any, changes
      were found in the 5' upstream (-706 to +135) promoter region. The results of the
      experiments support the null hypothesis that differences among individuals in the
      nucleotide and amino acid sequences of the promoter and coding regions of IA-2,
      respectively, do not account for why some individuals develop autoantibodies to
      IA-2 and others do not.

PMID- 11574428
TI  - A common hormone-sensitive lipase i6 gene polymorphism is associated with
      decreased human adipocyte lipolytic function.
AB  - Hereditary factors may be involved in the pathogenesis of type 2 diabetes. A
      polymorphism in the hormone-sensitive lipase (HSL) gene (HSLi6) is associated
      with obesity and diabetes, although it is unknown whether the polymorphism is
      functional and thereby influences lipolysis. We genotyped 355 apparently healthy
      nonobese male and female subjects for the HSLi6 polymorphism. Allele 5 was found
      to be the most common allele (allele frequency 0.57). In 117 of the subjects, we
      measured abdominal subcutaneous fat cell lipolysis induced by drugs acting at
      various steps in the lipolytic cascade. The lipolysis rate induced by
      norepinephrine isoprenaline (acting on beta-adrenoceptors), forskolin (acting on
      adenylyl cyclase), and dibutyryl cyclic AMP (acting on HSL) were all decreased by
      approximately 50% in allele 5 homozygotes, as compared with noncarriers.
      Heterozygotes showed an intermediate lipolytic rate. The difference in lipolysis
      rate between genotypes was more pronounced in men than in women. We conclude that
      allele 5 of the HSLi6 polymorphism is associated with a marked decrease in the
      lipolytic rate of abdominal fat cells. This may in turn contribute to the
      development of obesity.

PMID- 11574429
TI  - Theory in behavioral diabetes research.

PMID- 11574430
TI  - Insulin and glucose excursion following premeal insulin lispro or repaglinide in
      cystic fibrosis-related diabetes.
AB  - OBJECTIVE: Insulin and glucose levels in response to premeal insulin lispro or
      repaglinide were evaluated in adult patients with cystic fibrosis-related
      diabetes (CFRD) without fasting hyperglycemia. RESEARCH DESIGN AND METHODS: Seven
      patients with CFRD were fed 1,000-kcal liquid mixed meals. Three study conditions
      were administered in random order on separate mornings: 1) no premeal diabetes
      medication, 2) insulin lispro, 0.1 unit/kg body wt premeal and 3) repaglinide 1
      mg premeal. Glucose and insulin levels were measured every 20 min for 5 h.
      RESULTS: Fasting insulin and glucose levels were normal in patients with CFRD,
      but the peak glucose level was elevated. Insulin lispro significantly decreased
      the peak glucose level (P = 0.0004) and the 2-h (P = 0.001) and 5-h (P < 0.0001)
      glucose area under the curve (AUC). Repaglinide significantly decreased the 5-h
      glucose AUC (P = 0.03). Neither drug completely normalized cystic fibrosis
      glucose excursion at the doses used for this study. Insulin lispro significantly
      increased the 5-h insulin AUC (P = 0.04). CONCLUSIONS: In response to
      subcutaneous insulin lispro, postprandial glucose excursion was significantly
      diminished and insulin secretion was enhanced compared with a control meal in
      which no medication was given to patients with CFRD. The oral agent repaglinide
      resulted in lesser corrections in these parameters. Neither drug completely
      normalized glucose or insulin levels, suggesting that the doses chosen for this
      study were suboptimal. Placebo-controlled longitudinal studies comparing the
      effectiveness of repaglinide and insulin on glucose metabolic control as well as
      overall nutrition and body weight are needed to help determine optimal medical
      treatment of CFRD.

PMID- 11574431
TI  - Influence of intensive diabetes treatment on body weight and composition of
      adults with type 1 diabetes in the Diabetes Control and Complications Trial.
AB  - OBJECTIVE: To examine the differential effects of intensive and conventional
      diabetes therapy on weight gain and body composition in adults with type 1
      diabetes. RESEARCH DESIGN AND METHODS: Between 1982 and 1989, 1,246 adults (aged
      18-39 years) in the Diabetes Control and Complications Trial were randomly
      assigned to either conventional therapy (1-2 injections of insulin per day) or
      intensive therapy (multiple daily injections or continuous subcutaneous infusion
      with frequent blood-glucose testing). Height and weight were measured at baseline
      and at annual visits for an average of 6 years (range 3-9). Body composition was
      assessed cross-sectionally with bioelectrical impedance analysis during 1992, at
      which time waist and hip circumferences were measured. RESULTS: Intensively
      treated patients gained an average of 4.75 kg more than their conventionally
      treated counterparts (P < 0.0001). This represented excess increases in BMI of
      1.5 kg/m(2) among men and 1.8 kg/m(2) among women. Growth-curve analysis showed
      that weight gain was most rapid during the first year of therapy. Intensive
      therapy patients were also more likely to become overweight (BMI >or=27.8 kg/m(2)
      for men, >or=27.3 kg/m(2) for women) or experience major weight gain (BMI
      increased >or=5 kg/m(2)). Waist-to-hip ratios, however, did not differ between
      treatment groups. Major weight gain was associated with higher percentages of
      body fat and greater fat-free mass, but among patients without major weight gain,
      those receiving intensive therapy had greater fat-free mass with no difference in
      adiposity. CONCLUSIONS: Intensive therapy for type 1 diabetes produces
      substantial excess weight gain compared with conventional therapy. However, the
      additional weight appears to include lean tissue as well as fat.

PMID- 11574432
TI  - Intensive insulin therapy with insulin lispro: a randomized trial of continuous
      subcutaneous insulin infusion versus multiple daily insulin injection.
AB  - OBJECTIVE: To evaluate glycemic control, hypoglycemic events, and quality of life
      in patients treated with continuous subcutaneous insulin infusion (CSII) and
      multiple daily insulin injection (MDI), with insulin lispro as the principal
      insulin. RESEARCH DESIGN AND METHODS: This clinical trial enrolled 27 patients
      with type 1 diabetes. They were randomly assigned to CSII (n = 13) or MDI (n =
      14) treatment regimens. Glycemic control (HbA(1c) level) was the primary outcome
      and was measured monthly for 9 months. Secondary outcomes were patient reports of
      hypoglycemic events (recorded monthly for 9 months) and quality of life assessed
      at 9 months using the Diabetes Quality of Life (DQOL) questionnaire. RESULTS: A
      significant decrease in HbA(1c) from baseline was shown for both groups. However,
      the overall treatment effect (CSII - MDI) for HbA(1c) was +0.08% (95% CI -0.23 to
      +0.39, P > 0.10). This was significantly less than the a priori limit of +/-0.5%
      (P = 0.004). The relative treatment effect ([CSII - MDI]/MDI) for the overall
      number of hypoglycemic events was +9% (95% CI -37 to +87, P > 0.10). There were
      no statistically significant differences between treatment groups for any of the
      DQOL subscales. CONCLUSIONS: No statistically significant differences in glycemic
      control, reported hypoglycemic events, or quality of life were found in this
      study. Furthermore, a clinically significant difference of more than +/-0.5%
      HbA(1c) between the two regimens can be confidently ruled out. We conclude that
      the choice of intensive insulin therapy should be a matter of patient preference,
      consistent with lifestyle.

PMID- 11574433
TI  - Evidence-based guidelines meet the real world: the case of diabetes care.
AB  - OBJECTIVE: Improving diabetes care in the U.S. is critical because diabetes rates
      are increasing dramatically, particularly among minority and low-income
      populations. Although evidence-based practice guidelines for diabetes have been
      widely disseminated, many physicians fail to implement them. The objective of
      this study was to explore what happens to diabetes practice guidelines in real
      world clinical settings. RESEARCH DESIGN AND METHODS: A qualitative research
      design was used. Open-ended semistructured interviews lasting 1-2 h were
      conducted with 32 key informants (physicians, certified diabetes educators,
      researchers, and agency personnel) selected for their knowledge of diabetes care
      in South Texas, an area with a high diabetes prevalence and a large proportion of
      minority and low-income patients. RESULTS: Health professionals stress that
      contextual factors are more important barriers to optimal diabetes care than
      physician knowledge and attitudes. Barriers exist at multiple levels and are
      interrelated in a complex manner. Examples include the following: time
      constraints and practice economics in the private practice setting; the need to
      maintain referral relationships and maldistribution of professionals in the
      practice community; low awareness and low socioeconomic status among patients;
      and lack of access for low-income patients, low reimbursement, and insufficient
      focus on prevention in the U.S. health care system. CONCLUSIONS: Contextual
      barriers must be addressed in order for diabetes practice guidelines to be
      implemented in real-world clinical practice. Suggested changes include an
      increased focus on prevention, improvements in health care delivery for chronic
      diseases, and increased attention to the special needs of minority and low-income
      populations.

PMID- 11574434
TI  - Postchallenge hyperglycemia in a national sample of U.S. adults with type 2
      diabetes.
AB  - OBJECTIVE: Postchallenge hyperglycemia (PCH) is known to contribute to suboptimal
      glycemic control in adults with non-insulin-requiring type 2 diabetes. The
      objective of this study was to estimate the prevalence of PCH among individuals
      with diabetes. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional
      analysis of data from the Third National Health and Nutrition Examination Survey
      (1988-1994) in adults aged 40-74 years with diabetes who were not using insulin
      (i.e., they used oral hypoglycemics or received no pharmacological therapy). Each
      respondent underwent a standard 75-g oral glucose tolerance test. PCH was defined
      as a 2-h glucose level >or=200 mg/dl. RESULTS: Overall, PCH was present in 74% of
      those with diagnosed diabetes. Although it was present in virtually all (99%) of
      the diabetic adults under suboptimal glycemic control (HbA(1c) >or=7.0%), PCH was
      also common (39%) among those under optimal control (HbA(1c) <7.0%). Likewise,
      among sulfonylurea users, PCH was present in 99% of those under suboptimal
      control and in 63% of those under good control. Similar patterns were observed in
      those with undiagnosed diabetes. Isolated PCH (2-h glucose >or=200 mg/dl and
      fasting glucose <126 mg/dl) was present in 9.8% of the adults with diagnosed
      diabetes. CONCLUSIONS: These data suggest that PCH is common among diabetic
      adults in the U.S., even in the setting of "optimal" glycemic control and
      sulfonylurea use. Interventions designed to lower postprandial glucose excursions
      may help improve overall glycemic control in the general population of U.S.
      adults with diabetes.

PMID- 11574435
TI  - Pregnancy outcome in type 1 diabetic women with microalbuminuria.
AB  - OBJECTIVE: To determine the influence of microalbuminuria on pregnancy outcome in
      women with type 1 diabetes. RESEARCH DESIGN AND METHODS: This prospective cohort
      study took place at the Obstetric Clinic at National University Hospital,
      Copenhagen, from January 1996 to February 2000. All Caucasian women with type 1
      diabetes, unselected from the eastern part of Denmark, with a living fetus before
      17 weeks of gestation on admission were asked to participate. For women with more
      than one delivery in the study period, only the first pregnancy was included. Of
      the remaining 246 women, 240 (98%) entered the study. They were categorized
      according to their urinary albumin excretion (normal urinary albumin excretion,
      <30 mg/24 h; microalbuminuria, 30-300 mg/24 h; or diabetic nephropathy, >300
      mg/24 h) before pregnancy or in the first trimester. RESULTS: A total of 203
      women (85%) had normal urinary albumin excretion, 26 (11%) had microalbuminuria,
      and 11 (5%) had diabetic nephropathy. Mean HbA(1c) at 2-6 weeks was 7.5% (SD
      1.1), 8.1 (0.9), and 8.8 (1.3) (P < 0.001), respectively. Of all deliveries in
      women with normal urinary albumin excretion, microalbuminuria, and diabetic
      nephropathy, 35, 62, and 91% (P < 0.001), respectively, were preterm, and 2, 4,
      and 45% (P < 0.001), respectively, were small-for-gestational-age infants.
      Preeclampsia developed in 6, 42, and 64% of the women (P < 0.001), respectively.
      Category of urinary albumin excretion (P < 0.01) and HbA(1c) at 2-6 weeks (P <
      0.05) were independently associated with preterm delivery. CONCLUSIONS: The
      prevalence of preterm delivery is considerably increased in women with
      microalbuminuria, mainly caused by preeclampsia. Classification according to
      urinary albumin excretion and metabolic control around the time of conception are
      superior to the White classification in predicting preterm delivery in women with
      type 1 diabetes.

PMID- 11574436
TI  - Acute hypoglycemia in humans causes attentional dysfunction while nonverbal
      intelligence is preserved.
AB  - OBJECTIVE: Experimentally induced hypoglycemia in humans causes progressive but
      reversible cognitive dysfunction, but it is not known to what extent
      neuropsychological tests index abilities of cognitive functioning that are
      important in everyday life. This study examines the effects of acute insulin
      induced hypoglycemia on attention and intelligence in nondiabetic humans.
      RESEARCH DESIGN AND METHODS: A hyperinsulinemic glucose clamp was used to achieve
      controlled euglycemia (4.50 [0.22] mmol/l) and hypoglycemia (blood glucose 2.59
      [0.19] mmol/l) in 20 healthy volunteers. Subjects were studied on two occasions
      in a counterbalanced order. During each study condition, subjects completed
      parallel tests of cognitive function. Cognitive function was assessed by the Test
      of Everyday Attention and Raven's Progressive Matrices. RESULTS: Hypoglycemia
      induced a significant deterioration in tests sensitive to both visual and
      auditory selective attention. During hypoglycemia, attentional flexibility
      deteriorated and speed of information processing was delayed. Sustained attention
      was preserved and intelligence scores did not deteriorate during hypoglycemia.
      CONCLUSIONS: During hypoglycemia, a significant deterioration occurs in
      attentional abilities, whereas fluid intelligence is preserved. On the basis of
      these results, it can be surmised that many complex attention tasks relevant to
      everyday life are impaired during moderate hypoglycemia.

PMID- 11574437
TI  - Contributors to depression in Latino and European-American patients with type 2
      diabetes.
AB  - OBJECTIVE: To determine the independent and cumulative contributions of diabetes
      and other life stresses on depression and anxiety in Latino and European-American
      (EA) patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 75 Latino
      and 113 EA patients with type 2 diabetes, recruited from managed care settings,
      were assessed regarding three groups of potential stresses: demographics (age,
      sex, and education), disease status (functional impact, time since diagnosis,
      comorbidities, HbA(1c), and BMI), and family stress (financial stress, spouse
      conflict resolution, and family closeness). Dependent variables were depression
      (Center for Epidemiological Studies-Depression scale [CES-D]) and anxiety
      (Symptom Checklist [SCL-90]). Multiple regression equations assessed the
      independent contribution of each predictor on depression and anxiety. RESULTS:
      For both ethnic groups, education, functional impact, and financial stress
      significantly and independently predicted depression; poor spouse conflict
      resolution was a fourth significant predictor for EA patients only. The equations
      accounted for a high percentage of variance (43- 55%). Excluding education, the
      same variables predicted anxiety for both ethnic groups. The disease status and
      family stress variable groups significantly predicted outcomes independently. The
      relationships among these variables and depression and anxiety generally occurred
      for all patients, not only for those classified as likely depressed. CONCLUSIONS:
      The findings suggest the utility of considering many life stresses, not just
      diabetes alone, that combine to affect depression and anxiety. We suggest that
      these effects are experienced cumulatively as general psychological distress for
      all patients with diabetes, not just those classified as likely depressed. Taken
      together, the findings emphasize a life-centered, patient-focused approach to the
      treatment of depression, rather than an exclusive disease-related perspective.

PMID- 11574438
TI  - Do different dimensions of the metabolic syndrome change together over time?
      Evidence supporting obesity as the central feature.
AB  - OBJECTIVE: The metabolic syndrome is a loosely defined cluster of cardiovascular
      risk factors including low HDL cholesterol, hypertriglyceridemia, glucose
      intolerance, and hypertension. Evidence for inclusion of these features in the
      syndrome has mostly come from cross-sectional studies, and a few studies have
      examined how the various factors change together over time. RESEARCH DESIGN AND
      METHODS: We conducted a prospective population-based cohort study of 937
      individuals aged 40-65 years who underwent oral glucose tolerance testing on two
      occasions at 4.5-year intervals. Changes in the components of the metabolic
      syndrome were analyzed by principal component analysis in the entire population
      and in a subgroup of 471 individuals who did not receive pharmaceutical therapy
      for hypertension and dyslipidemia. RESULTS: Principal component analysis
      identified three independent factors in men: a blood pressure factor (systolic
      and diastolic blood pressure and BMI), a glucose factor (fasting and 120-min
      postload glucose, BMI, waist-to-hip ratio [WHR], and fasting insulin level), and
      a lipid factor (triglycerides and HDL cholesterol, BMI, WHR, and fasting insulin
      level). In women, an additional factor was identified, which included BMI, WHR,
      fasting insulin, and triglycerides. Analysis of the contribution of these
      variables to the different subdimensions indicated that BMI was the central
      feature of the syndrome in both sexes. CONCLUSIONS: This analysis of change in
      the features of the metabolic syndrome over time provides evidence of the
      fundamental importance of obesity in the origin of this disorder.

PMID- 11574439
TI  - Prevalence and risk factors of microalbuminuria in a cohort of African-American
      women with gestational diabetes.
AB  - OBJECTIVE: To study the prevalence of microalbuminuria (MA) in African-American
      women with a history of gestational diabetes (GDM) who are at high risk for
      insulin resistance and renal dysfunction and to study MA's relation to insulin
      resistance, type 2 diabetes, and hypertension. RESEARCH DESIGN AND METHODS: MA
      was assessed using 24-h, timed, and/or random urine samples in a cross-sectional
      sample (n = 289) from a cohort of African-American women with a history of GDM
      and followed for a median of 11 years (range 3.0-18.4) since their diabetic
      pregnancy. Subjects with a urine albumin excretion rate of 30-300 g/24 h or 30
      300 microg/mg creatinine in a random sample were classified as having MA if two
      of three samples over a 3- to 6-month period were positive. These women were
      evaluated for family history of diabetes, smoking and alcohol use, BMI, diabetes,
      hypertension, and lipid abnormalities. Insulin sensitivity was determined using
      the homeostasis model assessment (HOMA) estimates, which used fasting insulin and
      glucose measurements obtained at the same time as the MA urine sample. RESULTS:
      At MA assessment, the women ranged in age from 22 to 57 years, with a median of
      39 years. The overall prevalence of MA was 20%; 36% in those with diabetes. Those
      women with MA had higher rates of diabetes (63.8 vs. 28.6%, odds ratio [OR] =
      4.4, P < 0.05), hypertension (82.8 vs. 42.9%, OR = 6.4, P < 0.05), and family
      history of diabetes (85.7 vs. 61.7%, OR = 3.7, P < 0.05). The proportion of
      subjects with MA with a family history of hypertension was nonsignificantly
      increased (92.9 vs. 82.4%). Subjects with MA were more obese (BMI 37.2 +/- 8.9
      vs. 34.4 +/- 8.6 kg/m(2)) and had higher levels of HbA(1c) (8.8 +/- 3.3 vs. 6.6
      +/- 1.8%, P < 0.001) and systolic (144.3 +/- 25.9 vs. 122.8 +/- 17.2 mmHg, P <
      0.0001) and diastolic (95.1 +/- 15.4 vs. 82.5 +/- 11.9 mmHg, P < 0.0001) blood
      pressures. Lipid fractions were similar in those with and without MA. Although
      fasting glucose was much higher in subjects with MA (10.3 +/- 5.8 vs. 7.1 +/- 4.2
      mmol/l, P = 0.0002), insulin levels were not significantly higher in subjects
      with MA (17.4 +/- 21.2 vs. 15.2 +/- 12.4 pmol/l). Insulin sensitivity, as
      measured using log HOMA, was similar (1.5 +/- 0.6 vs. 1.6 +/- 0.6) in women with
      and without MA, respectively. Multivariable logistic regression analyses
      indicated that HbA(1c), OR = 1.16 (1.07, 1.27), and systolic blood pressure, OR =
      1.27 (1.14, 1.41), were independent risk factors for MA. In those with diabetes,
      the subjects with MA had higher rates of hypertension-83.8 vs. 56.1%, OR = 4.1
      (1.5, 11.10)-which was reflected by their higher systolic and diastolic blood
      pressures, 146.1 mmHg (P = 0.001) and 94.8 mmHg (P = 0.002), respectively, and
      lower levels of VLDL (0.45 +/- 0.22 vs. 0.61 +/- 0.33 mmol/l, P = 0.021). In the
      multivariable analyses of those with diabetes, the two independent risk factors
      for MA were similar: HbA(1c), OR = 1.13 (1.01, 1.28), and systolic blood
      pressure, OR = 1.21 (1.04, 1.41). CONCLUSIONS: African-American women with a
      history of GDM have one of the highest rates for MA. Presence of MA was not
      associated with insulin resistance but was significantly independently associated
      with HbA(1c) levels and hypertension. These results, taken in context of the
      literature, suggest that hypertension and glucose intolerance, in part, influence
      MA through different mechanisms. Because of the high prevalence of MA in this
      population and MA's relation to all-cause and cardiovascular mortality, screening
      for MA should be considered.

PMID- 11574440
TI  - Mediators of lifestyle behavior change in Native Hawaiians: initial findings from
      the Native Hawaiian Diabetes Intervention Program.
AB  - OBJECTIVE: To examine the association of stage of change with diet and exercise
      behaviors in response to a lifestyle intervention for Native Hawaiians (NHs).
      RESEARCH DESIGN AND METHODS: A family ('ohana) support lifestyle intervention was
      compared with a standard intervention in NHs with or at risk for diabetes in two
      rural communities in Hawaii (n = 147). Stage of change, as a hypothesized
      mediator of behavior change, and dietary and exercise behaviors were measured at
      baseline and at 1 year postintervention. RESULTS: Stage of change was
      significantly associated with positive dietary and exercise behaviors. NHs
      receiving the 'ohana support (OS) intervention were more likely to advance from
      pre-action to action/maintenance for fat intake and physical activity than the
      group who received the standard intervention. Participants in the OS group who
      advanced from pre-action to action/maintenance showed more improvement in fat
      intake and physical activity than those in the standard group. CONCLUSIONS: These
      initial findings suggest that stage of change is an important factor in mediating
      lifestyle behavior changes in persons with or at risk for diabetes and merits
      further study among minority populations at high risk for diabetes.

PMID- 11574442
TI  - Orthostatic hypertension in patients with type 2 diabetes.
AB  - OBJECTIVE: The prevalence and clinical importance of orthostatic hypertension
      (OHT) in diabetic patients has not been elucidated, in contrast to orthostatic
      hypotension, which is occasionally found in diabetic patients with autonomic
      neuropathy. RESEARCH DESIGN AND METHODS: The prevalence and severity of
      orthostatic hypertension was investigated in 277 Japanese male patients with type
      2 diabetes, including 90 hypertensive patients and 128 nondiabetic age-matched
      male subjects. Patients treated with antihypertensive drugs were excluded from
      the study. OHT was defined as an increase in diastolic blood pressure (DBP) from
      <90 to >or=90 mmHg and/or an increase in systolic blood pressure (SBP) from <140
      to >or=140 mmHg after standing from supine position. Clinical profiles and
      several serum biochemical parameters were determined in addition to chest X-rays
      and electrocardiograms. RESULTS: The prevalence of OHT in normotensive and
      hypertensive diabetic patients was significantly higher than in control subjects
      (12.8 vs. 1.8%, P < 0.01, for normotensive patients; 12.6 vs. 11.1%, not
      significant, for hypertensive patients). Orthostasis induced a mean increase of
      6.8 +/- 11.4 mmHg in SBP and 9.1 +/- 5.2 mmHg in DBP in diabetic patients with
      OHT compared with those without OHT (-1.0 +/- 9.0 and 3.8 +/- 6.6 mmHg,
      respectively). Vibration sensation in the lower limb was reduced in diabetic
      patients with OHT, but the percent coefficient of variation of RR interval,
      cardio-to-thoracic ratio on chest X-ray, and serum triglyceride levels were
      higher in these patients compared with normotensive diabetic patients without
      OHT. CONCLUSIONS: Orthostatic hypertension is a novel complication in
      normotensive diabetic patients and may associate with early stage neuropathy and
      development of sustained hypertension.

PMID- 11574441
TI  - Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic
      peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind
      parallel group study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of fidarestat,
      a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled
      study in patients with type 1 and type 2 diabetes and associated peripheral
      neuropathy. RESEARCH DESIGN AND METHODS: A total of 279 patients with diabetic
      neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52
      weeks. The efficacy evaluation was based on change in electrophysiological
      measurements of median and tibial motor nerve conduction velocity, F-wave minimum
      latency, F-wave conduction velocity (FCV), and median sensory nerve conduction
      velocity (forearm and distal), as well as an assessment of subjective symptoms.
      RESULTS: Over the course of the study, five of the eight electrophysiological
      measures assessed showed significant improvement from baseline in the fidarestat
      treated group, whereas no measure showed significant deterioration. In contrast,
      in the placebo group, no electrophysiological measure was improved, and one
      measure significantly deteriorated (i.e., median nerve FCV). At the study
      conclusion, the fidarestat-treated group was significantly improved compared with
      the placebo group in two electrophysiological measures (i.e., median nerve FCV
      and minimal latency). Subjective symptoms (including numbness, spontaneous pain,
      sensation of rigidity, paresthesia in the sole upon walking, heaviness in the
      foot, and hypesthesia) benefited from fidarestat treatment, and all were
      significantly improved in the treated versus placebo group at the study
      conclusion. At the dose used, fidarestat was well tolerated, with an adverse
      event profile that did not significantly differ from that seen in the placebo
      group. CONCLUSIONS: The effects of fidarestat-treatment on nerve conduction and
      the subjective symptoms of diabetic neuropathy provide evidence that this
      treatment alters the progression of diabetic neuropathy.

PMID- 11574443
TI  - Physical activity, physical fitness, and insulin and glucose concentrations in an
      isolated Native Canadian population experiencing rapid lifestyle change.
AB  - OBJECTIVE: Little is known about the relation of physical activity and physical
      fitness to insulin resistance and glucose intolerance in isolated subarctic
      Native Canadian populations. The purpose of this effort was to examine the
      relation between activity and fitness and obesity and glucose concentrations in
      such a unique population. RESEARCH DESIGN AND METHODS: This study describes 530
      men and women from the community of Sandy Lake, Ontario, located in the boreal
      forest region of central Canada. Fasting blood glucose and insulin concentrations
      were determined after an overnight fast. Past year physical activity levels were
      assessed using a modified version of an interviewer-administered questionnaire.
      Maximal oxygen uptake, a measure of cardiovascular fitness, was estimated using a
      submaximal step test. RESULTS: Total (leisure and occupational) physical activity
      and physical fitness were significantly associated with fasting insulin
      concentrations after adjusting for age, BMI or percent body fat, waist
      circumference, and fasting glucose concentration in men but not in women. The
      relations between physical activity, fitness, and fasting glucose concentrations
      were not as strong or as consistent as they were when fasting insulin
      concentration was the dependent variable. CONCLUSIONS: In this isolated Native
      Canadian community, both physical activity and fitness were independently
      associated with fasting insulin concentrations, suggesting a beneficial role of
      physical activity/fitness on insulin sensitivity that is separate from any
      influence of activity on body composition. The fact that this relation was found
      in men but not in women is most likely explained by issues related to the
      measurement of activity and fitness in this study and the fact that the women in
      this population appear to be less active than the men.

PMID- 11574444
TI  - Impaired autonomic function is associated with increased mortality, especially in
      subjects with diabetes, hypertension, or a history of cardiovascular disease: the
      Hoorn Study.
AB  - OBJECTIVE: Measures of baroreflex sensitivity, heart rate variability (HRV), and
      the classical Ewing test parameters are currently used for the diagnosis of
      diabetic autonomic neuropathy and for mortality risk stratification after
      myocardial infarction. However, the strengths of the associations of these
      measures of autonomic function with risk of mortality have never been compared in
      one study population. Furthermore, no evidence is available on the possible
      effect of glucose tolerance on these associations. RESEARCH DESIGN AND METHODS:
      The study population (n = 605) consisted of a glucose tolerance-stratified sample
      from a general population (50-75 years of age). Cardiac cycle duration and
      continuous finger arterial pressure were measured under two conditions: at rest
      and on metronome breathing. From these readings, seven parameters of autonomic
      function were assessed (one Ewing, five HRV, and one baroreflex sensitivity).
      RESULTS: During 9 years of follow-up, 101 individuals died, 43 from
      cardiovascular causes. Subjects with diabetes and low levels of the autonomic
      function parameters, indicating impaired autonomic function, had an approximately
      doubled risk of mortality. This association was consistent, though not
      statistically significant, for all parameters. The elevated risk was not observed
      in subjects without diabetes, hypertension, or prevalent cardiovascular disease.
      CONCLUSIONS: Impaired autonomic function is associated with all-cause and
      cardiovascular mortality. Moreover, the results of the present study suggest that
      cardiac autonomic dysfunction in patients already at risk (diabetes,
      hypertension, or history of cardiovascular disease) may be especially hazardous.

PMID- 11574445
TI  - Functional status of persons with diabetes-related lower-extremity amputations.
AB  - OBJECTIVE: It is reasonable to predict that diabetes-related lower-extremity
      amputations have a detrimental impact on quality of life. However, we are unaware
      of any study in the medical literature describing the functional level of
      diabetic patients with amputations. The objective of this study was to evaluate
      amputations among diabetic patients and to determine the functional level of
      these patients with the Sickness Impact Profile (SIP). RESEARCH DESIGN AND
      METHODS: We enrolled 124 patients with diabetes. Case subjects (n = 35) were
      defined as patients who had undergone amputation of the lower-extremity, and
      control subjects (n = 89) were defined as patients who had not undergone
      amputation. Study participants received a standard history and physical
      examination. RESULTS: Both the physical dimension scores (33.5 +/- 14.9 vs. 22.3
      +/- 14.7, P < 0.001) and the total SIP scores (27.6 +/- 9.9 vs. 22.5 +/- 10.3, P
      = 0.013) were significantly higher for amputees. However, the psychosocial
      dimension scores were not significantly different between case and control
      subjects (14.9 +/- 8.9 vs. 15.2 +/- 10.0, P > 0.05). Post hoc analysis showed
      that the group of patients who had undergone transtibial amputation had a
      significantly higher total impairment score than patients who had not undergone
      amputation (P = 0.039). This is in contrast to patients with toe or midfoot
      amputations, for whom total impairment scores were not significantly higher than
      those for the control subjects. Interestingly, bilateral amputees did not have
      significantly higher scores on either SIP dimension compared with unilateral
      amputees. CONCLUSIONS: These findings exemplify the detrimental physical and
      psychosocial health status of patients with diabetes-related lower-extremity
      amputation.

PMID- 11574446
TI  - The relationship among homocysteine, creatinine clearance, and albuminuria in
      patients with type 2 diabetes.
AB  - OBJECTIVE: Although it is accepted that elevated plasma homocysteine (tHcy)
      levels occur in end-stage renal disease and type 2 diabetes, the changes with
      milder renal dysfunction (e.g., microalbuminuria) are less clearly established.
      This study explores the relationship among tHcy, creatinine clearance (Ccr), and
      albumin excretion rate (AER) in a population with type 2 diabetes. RESEARCH
      DESIGN AND METHODS: A total of 260 patients with type 2 diabetes were screened in
      our outpatient clinic during 10 months. Fasting blood samples were collected, and
      AER was calculated from an overnight timed urine sample. Ccr was calculated using
      the Cockroft-Gault formula. RESULTS: A total of 198 subjects (76%) had
      normoalbuminuria (<20 microg/min), 50 subjects (19%) had microalbuminuria (20-200
      microg/min), and 12 subjects (5%) had macroalbuminuria (>or=200 microg/min).
      Those with microalbuminuria had higher levels of tHcy than those with
      normoalbuminuria (13.2 +/- 7.8 vs. 11.3 +/- 4.6 micromol/l, P < 0.05). Patients
      were then subdivided based on low Ccr (<80 ml x min(-1) x 1.73 m(-2)) and normal
      Ccr (>or=80 x min(-1) x 1.73 m(-2)). None of the patients with macroalbuminuria
      had normal Ccr. In those with normoalbuminuria, tHcy levels were higher than in
      those with low Ccr than in those with normal Ccr (12.0 +/- 4.6 vs. 10.0 +/- 4.4
      micromol/l, P < 0.01). The same was found for those with microalbuminuria (low
      Ccr versus normal Ccr: 14.6 +/- 9.0 vs. 10.2 +/- 2.8 micromol/l, P < 0.02). For
      normal Ccr, tHcy was similar irrespective of AER (normoalbuminuria versus
      microalbuminuria: 10.0 +/- 4.4 vs. 10.2 +/- 2.8 micromol/l, NS). For low Ccr,
      tHcy was higher in those with microalbuminuria versus normoalbuminuria (14.6 +/-
      9.0 vs. 12.0 +/- 4.6 micromol/l, P = 0.01). Using multivariate regression, Ccr,
      but neither AER nor the presence of albuminuria, was an independent predictor of
      tHcy. CONCLUSIONS: These data strongly suggest that in patients with type 2
      diabetes, the relationship between plasma tHcy and AER is largely due to
      associated changes in renal function, as defined by Ccr.

PMID- 11574447
TI  - Early detection of microcirculatory impairment in diabetic patients with foot at
      risk.
AB  - OBJECTIVE: To assess microcirculatory impairment and alterations of the skin
      oxygen supply in diabetic patients with foot at risk. RESEARCH DESIGN AND
      METHODS: This study evaluated skin blood flow in 21 type 2 diabetic patients with
      a foot at risk (defined as a foot with neuropathy but without ulceration or
      previous ulcerations), 20 type 2 diabetic patients without foot lesions or
      neuropathy, and 21 normal subjects as a control group. The skin blood flow was
      determined by measuring the transcutaneous oxygen pressure (TcPO(2)) at the
      dorsum of the foot in supine and sitting position. The clinical assessment
      included standard measures of peripheral and autonomic neuropathy, but peripheral
      vascular disease was excluded by Doppler ultrasound. RESULTS: In supine position,
      TcPO(2) was significantly reduced (means +/- SE) in diabetic patients with foot
      at risk (6.04 +/- 0.52 kPa) compared with diabetic (7.14 +/- 0.43 kPa, P = 0.035)
      and nondiabetic (8.10 +/- 0.44 kPa, P = 0.01) control subjects. The
      sitting/supine TcPO(2) difference was higher in diabetic subjects with foot at
      risk (3.13 +/- 0.27 kPa) compared with both diabetic (2.00 +/- 0.18, P = 0.004)
      and nondiabetic (1.77 +/- 0.15 kPa, P = 0.0003) control subjects. The mean
      sitting/supine ratio was 1.70 +/- 0.12 in diabetic patients with foot at risk,
      1.32 +/- 0.04 in diabetic control subjects, and 1.25 +/- 0.03 in nondiabetic
      control subjects (P = 0.007). The sitting/supine TcPO(2) ratio was negatively
      correlated with the heart rate variation coefficient at rest (r = -0.32, P =
      0.044) and at deep respiration (r = -0.31, P = 0.046). CONCLUSIONS: Our data
      indicate that skin oxygen supply is reduced in type 2 diabetic patients with foot
      at risk. This is probably due to an impaired neurogenic blood flow regulation and
      may contribute to capillary hypertension, followed by disturbed endothelial
      function leading to edema and skin damage of the foot. The determination of
      TcPO(2) appears to be a useful tool in screening type 2 diabetic patients for
      foot at risk.

PMID- 11574448
TI  - The Diabetes Quality Improvement Project: moving science into health policy to
      gain an edge on the diabetes epidemic.

PMID- 11574449
TI  - Interventions to improve the management of diabetes in primary care, outpatient,
      and community settings: a systematic review.
AB  - OBJECTIVE: To review the effectiveness of interventions targeted at health care
      professionals and/or the structure of care in order to improve the management of
      diabetes in primary care, outpatient, and community settings. RESEARCH DESIGN AND
      METHODS: A systematic review of controlled trials evaluating the effectiveness of
      interventions targeted at health care professionals and aimed at improving the
      process of care or patient outcomes for patients with diabetes was performed.
      Standard search methods of the Cochrane Effective Practice and Organization of
      Care Group were used. RESULTS: A total of 41 studies met the inclusion criteria.
      The studies identified were heterogeneous in terms of interventions,
      participants, settings, and reported outcomes. In all studies, the interventions
      were multifaceted. The interventions were targeted at health care professionals
      only in 12 studies, at the organization of care only in 9 studies, and at both in
      20 studies. Complex professional interventions improved the process of care, but
      the effect on patient outcomes remained less clear because such outcomes were
      rarely assessed. Organizational interventions that facilitated the structured and
      regular review of patients also showed a favorable effect on process measures.
      Complex interventions in which patient education was added and/or the role of a
      nurse was enhanced led to improvements in patient outcomes as well as the process
      of care. CONCLUSIONS: Multifaceted professional interventions and organizational
      interventions that facilitate structured and regular review of patients were
      effective in improving the process of care. The addition of patient education to
      these interventions and the enhancement of the role of nurses in diabetes care
      led to improvements in patient outcomes and the process of care.

PMID- 11574450
TI  - Angiotensin II receptor blockers and nephropathy trials.

PMID- 11574451
TI  - Blood catalase deficiency and diabetes in Hungary.

PMID- 11574452
TI  - Don't ignore the patients.

PMID- 11574453
TI  - Immune responses to hepatitis B vaccine with and without the pre-S2 antigen in
      children with type 1 diabetes.

PMID- 11574454
TI  - The American Diabetes Association should be a leader in reducing medication
      errors.

PMID- 11574455
TI  - Proinsulin-specific autoantibodies are relatively infrequent in young offspring
      with pre-type 1 diabetes.

PMID- 11574456
TI  - Effect of repaglinide addition to NPH insulin monotherapy on glycemic control in
      patients with type 2 diabetes.

PMID- 11574457
TI  - Loss of awareness of hypoglycemia temporally associated with selective serotonin
      reuptake inhibitors.

PMID- 11574458
TI  - Genetic and environmental factors for type 1 diabetes: data from the province of
      Oristano, Sardinia, Italy.

PMID- 11574459
TI  - Serum nonesterified fatty acids are increased in nonobese Japanese type 2
      diabetic patients with microalbuminuria.

PMID- 11574460
TI  - Insulin therapy does not itself induce weight gain in patients with type 2
      diabetes.

PMID- 11574461
TI  - The crystal structure of Sulfolobus solfataricus elongation factor 1alpha in
      complex with GDP reveals novel features in nucleotide binding and exchange.
AB  - The crystal structure of elongation factor 1alpha from the archaeon Sulfolobus
      solfataricus in complex with GDP (SsEF-1alpha.GDP) at 1.8 A resolution is
      reported. As already known for the eubacterial elongation factor Tu, the SsEF
      1alpha.GDP structure consists of three different structural domains.
      Surprisingly, the analysis of the GDP-binding site reveals that the nucleotide-
      protein interactions are not mediated by Mg(2+). Furthermore, the residues that
      usually co-ordinate Mg(2+) through water molecules in the GTP-binding proteins,
      though conserved in SsEF-1alpha, are located quite far from the binding site.
      [(3)H]GDP binding experiments confirm that Mg(2+) has only a marginal effect on
      the nucleotide exchange reaction of SsEF-1alpha, although essential to GTPase
      activity elicited by SsEF-1alpha. Finally, structural comparisons of SsEF-
      1alpha.GDP with yeast EF-1alpha in complex with the nucleotide exchange factor EF
      1beta shows that a dramatic rearrangement of the overall structure of EF-1alpha
      occurs during the nucleotide exchange.

PMID- 11574462
TI  - Structural insights into the early steps of receptor-transducer signal transfer
      in archaeal phototaxis.
AB  - Electron paramagnetic resonance-based inter-residue distance measurements between
      site-directed spin-labelled sites of sensory rhodopsin II (NpSRII) and its
      transducer NpHtrII from Natronobacterium pharaonis revealed a 2:2 complex with 2
      fold symmetry. The core of the complex is formed by the four transmembrane
      helices of a transducer dimer. Upon light excitation, the previously reported
      flap-like movement of helix F of NpSRII induces a conformational change in the
      transmembrane domain of the transducer. The inter-residue distance changes
      determined provide strong evidence for a rotary motion of the second
      transmembrane helix of the transducer. This helix rotation becomes uncoupled from
      changes in the receptor during the last step of the photocycle.

PMID- 11574463
TI  - Crystal structure of human protein kinase CK2: insights into basic properties of
      the CK2 holoenzyme.
AB  - The crystal structure of a fully active form of human protein kinase CK2 (casein
      kinase 2) consisting of two C-terminally truncated catalytic and two regulatory
      subunits has been determined at 3.1 A resolution. In the CK2 complex the
      regulatory subunits form a stable dimer linking the two catalytic subunits, which
      make no direct contact with one another. Each catalytic subunit interacts with
      both regulatory chains, predominantly via an extended C-terminal tail of the
      regulatory subunit. The CK2 structure is consistent with its constitutive
      activity and with a flexible role of the regulatory subunit as a docking partner
      for various protein kinases. Furthermore it shows an inter-domain mobility in the
      catalytic subunit known to be functionally important in protein kinases and
      detected here for the first time directly within one crystal structure.

PMID- 11574464
TI  - IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL
      17F, and implications for receptor binding.
AB  - The proinflammatory cytokine interleukin 17 (IL-17) is the founding member of a
      family of secreted proteins that elicit potent cellular responses. We report a
      novel human IL-17 homolog, IL-17F, and show that it is expressed by activated T
      cells, can stimulate production of other cytokines such as IL-6, IL-8 and
      granulocyte colony-stimulating factor, and can regulate cartilage matrix
      turnover. Unexpectedly, the crystal structure of IL-17F reveals that IL-17 family
      members adopt a monomer fold typical of cystine knot growth factors, despite
      lacking the disulfide responsible for defining the canonical "knot" structure. IL
      17F dimerizes in a parallel manner like neurotrophins, and features an unusually
      large cavity on its surface. Remarkably, this cavity is located in precisely the
      same position where nerve growth factor binds its high affinity receptor, TrkA,
      suggesting further parallels between IL-17s and neurotrophins with respect to
      receptor recognition.

PMID- 11574465
TI  - Structural basis for the high-affinity interaction of nidogen-1 with
      immunoglobulin-like domain 3 of perlecan.
AB  - Nidogen and perlecan are large multifunctional basement membrane (BM) proteins
      conserved in all metazoa. Their high-affinity interaction, which is likely to
      contribute to BM assembly and function, is mediated by the central G2 domain in
      nidogen and the third immunoglobulin (IG)-like domain in perlecan, IG3. We have
      solved the crystal structure at 2.0 A resolution of the mouse nidogen-1 G2
      perlecan IG3 complex. Perlecan IG3 belongs to the I-set of the IG superfamily and
      binds to the wall of the nidogen-1 G2 beta-barrel using beta-strands C, D and F.
      Nidogen-1 residues participating in the extensive interface are highly conserved,
      whereas the corresponding binding site on perlecan is more variable. We
      hypothesize that a second, as yet unidentified, activity of nidogen overlaps with
      perlecan binding and accounts for the unusually high degree of surface
      conservation in the G2 domain.

PMID- 11574466
TI  - NMR structure of the LCCL domain and implications for DFNA9 deafness disorder.
AB  - The LCCL domain is a recently discovered, conserved protein module named after
      its presence in Limulus factor C, cochlear protein Coch-5b2 and late gestation
      lung protein Lgl1. The LCCL domain plays a key role in the autosomal dominant
      human deafness disorder DFNA9. Here we report the nuclear magnetic resonance
      (NMR) structure of the LCCL domain from human Coch-5b2, where dominant mutations
      leading to DFNA9 deafness disorder have been identified. The fold is novel. Four
      of the five known DFNA9 mutations are shown to involve at least partially solvent
      exposed residues. Except for the Trp91Arg mutant, expression of these four LCCL
      mutants resulted in misfolded proteins. These results suggest that Trp91
      participates in the interaction with a binding partner. The unexpected
      sensitivity of the fold with respect to mutations of solvent-accessible residues
      might be attributed to interference with the folding pathway of this disulfide
      containing domain.

PMID- 11574467
TI  - Exon structure conservation despite low sequence similarity: a relic of dramatic
      events in evolution?
AB  - The evolutionary significance of introns remains a mystery. The current
      availability of several complete eukaryotic genomes permits new studies to probe
      the possible function of these peculiar genomic features. Here we investigate the
      degree to which gene structure (intron position, phase and length) is conserved
      between homologous protein domains. We find that for certain extracellular
      signalling and nuclear domains, gene structures are similar even when protein
      sequence similarity is low or not significant and sequences can only be aligned
      with a knowledge of protein tertiary structure. In contrast, other domains,
      including most intracellular signalling modules, show little gene structure
      conservation. Intriguingly, many domains with conserved gene structures, such as
      cytokines, are involved in similar biological processes, such as the immune
      response. This suggests that gene structure conservation may be a record of key
      events in evolution, such as the origin of the vertebrate immune system or the
      duplication of nuclear receptors in nematodes. The results suggest ways to detect
      new and potentially very remote homologues, and to construct phylogenies for
      proteins with limited sequence similarity.

PMID- 11574468
TI  - Impaired wound healing in transgenic mice overexpressing the activin antagonist
      follistatin in the epidermis.
AB  - Recently, we demonstrated a strong upregulation of activin expression after skin
      injury. Furthermore, overexpression of this transforming growth factor beta
      family member in the skin of transgenic mice caused dermal fibrosis, epidermal
      hyperthickening and enhanced wound repair. However, the role of endogenous
      activin in wound healing has not been determined. To address this question we
      overexpressed the soluble activin antagonist follistatin in the epidermis of
      transgenic mice. These animals were born with open eyes, and the adult mice had
      larger ears, longer tails and reduced body weight compared with non-transgenic
      littermates. Their skin was characterized by a mild dermal and epidermal atrophy.
      After injury, a severe delay in wound healing was observed. In particular,
      granulation tissue formation was significantly reduced, leading to a major
      reduction in wound breaking strength. The wounds, however, finally healed, and
      the resulting scar area was smaller than in control animals. These results
      implicate an important function of endogenous activin in the control of wound
      repair and scar formation.

PMID- 11574469
TI  - A bacterial type III secretion system inhibits actin polymerization to prevent
      pore formation in host cell membranes.
AB  - The bacterial pathogen Yersinia pseudotuberculosis uses type III secretion
      machinery to translocate Yop effector proteins through host cell plasma
      membranes. A current model suggests that a type III translocation channel is
      inserted into the plasma membrane, and if Yops are not present to fill the
      channel, the channel will form a pore. We examined the possibility that Yops act
      within the host cell to prevent pore formation. Yop- mutants of
      Y.pseudotuberculosis were assayed for pore-forming activity in HeLa cells. A YopE
      mutant exhibited high levels of pore-forming activity. The GTPase-downregulating
      function of YopE was required to prevent pore formation. YopE+ bacteria had
      increased pore-forming activity when HeLa cells expressed activated Rho GTPases.
      Pore formation by YopE- bacteria required actin polymerization. F-actin was
      concentrated at sites of contact between HeLa cells and YopE- bacteria. The data
      suggest that localized actin polymerization, triggered by the type III machinery,
      results in pore formation in cells infected with YopE- bacteria. Thus,
      translocated YopE inhibits actin polymerization to prevent membane damage to
      cells infected with wild-type bacteria.

PMID- 11574470
TI  - Proteasomes and ubiquitin are involved in the turnover of the wild-type prion
      protein.
AB  - Prion diseases propagate by converting a normal glycoprotein of the host, PrP(C),
      into a pathogenic "prion" conformation. Several misfolding mutants of PrP(C) are
      degraded through the ER-associated degradation (ERAD)-proteasome pathway. In
      their infectious form, prion diseases such as bovine spongiform encephalopathy
      involve PrP(C) of wild-type sequence. In contrast to mutant PrP, wild-type PrP(C)
      was hitherto thought to be stable in the ER and thus immune to ERAD. Using
      proteasome inhibitors, we now show that approximately 10% of nascent PrP(C)
      molecules are diverted into the ERAD pathway. Cells incubated with N-acetyl
      leucinal-leucinal-norleucinal (ALLN), lactacystin or MG132 accumulated both
      detergent-soluble and insoluble PrP species. The insoluble fraction included an
      unglycosylated 26 kDa PrP species with a protease-resistant core, and a M(r)
      "ladder" that contained ubiquitylated PrP. Our results show for the first time
      that wild-type PrP(C) molecules are subjected to ERAD, in the course of which
      they are dislocated into the cytosol and ubiquitylated. The presence of wild-type
      PrP molecules in the cytosol may have potential pathogenic implications.

PMID- 11574471
TI  - Repression of deoP2 in Escherichia coli by CytR: conversion of a transcription
      activator into a repressor.
AB  - In the deoP2 promoter of Escherichia coli, a transcription activator, cAMP-CRP,
      binds at two sites, centered at -41.5 and -93.5 from the start site of
      transcription, while a repressor, CytR, binds to a space between the two cAMP-CRP
      complexes. The mechanisms for the cAMP-CRP-mediated transcription activation and
      CytR-mediated transcription repression were investigated in vitro using purified
      components. We classified the deoP2 promoter as a class II cAMP-CRP-dependent
      promoter, primarily by the action of cAMP-CRP at the downstream site.
      Interestingly, we also found that deoP2 carries an "UP-element" immediately
      upstream of the downstream cAMP-CRP site. The UP-element overlaps with the DNA
      site for CytR. However, it was observed that CytR functions with the RNA
      polymerase devoid of the C-terminal domain of the alpha-subunit as well as with
      intact RNA polymerase. The mechanism of repression by CytR proposed in this study
      is that the cAMP-CRP bound at -41.5 undergoes an allosteric change upon direct
      interaction with CytR such that it no longer maintains a productive interaction
      with the N-terminal domain of alpha, but instead acts as a repressor to interfere
      with RNA polymerase acting on deoP2.

PMID- 11574472
TI  - Direct interaction between the Arabidopsis disease resistance signaling proteins,
      EDS1 and PAD4.
AB  - The Arabidopsis EDS1 and PAD4 genes encode lipase-like proteins that function in
      resistance (R) gene-mediated and basal plant disease resistance. Phenotypic
      analysis of eds1 and pad4 null mutants shows that EDS1 and PAD4 are required for
      resistance conditioned by the same spectrum of R genes but fulfil distinct roles
      within the defence pathway. EDS1 is essential for elaboration of the plant
      hypersensitive response, whereas EDS1 and PAD4 are both required for accumulation
      of the plant defence-potentiating molecule, salicylic acid. EDS1 is necessary for
      pathogen-induced PAD4 mRNA accumulation, whereas mutations in PAD4 or depletion
      of salicylic acid only partially compromise EDS1 expression. Yeast two-hybrid
      analysis reveals that EDS1 can dimerize and interact with PAD4. However, EDS1
      dimerization is mediated by different domains to those involved in EDS1-PAD4
      association. Co-immunoprecipitation experiments show that EDS1 and PAD4 proteins
      interact in healthy and pathogen-challenged plant cells. We propose two functions
      for EDS1. The first is required early in plant defence, independently of PAD4.
      The second recruits PAD4 in the amplification of defences, possibly by direct
      EDS1-PAD4 association.

PMID- 11574473
TI  - The osmoreactive betaine carrier BetP from Corynebacterium glutamicum is a sensor
      for cytoplasmic K+.
AB  - The isolated glycine betaine uptake carrier BetP from Corynebacterium glutamicum
      was reconstituted in Escherichia coli phospholipid liposomes and its response to
      osmotic stress studied. The transport activity of BetP, which was previously
      shown to comprise both osmosensory and osmoregulatory functions, was used to
      identify the nature of the physicochemical stimulus related to hyperosmotic
      stress. Putative factors modulating transport activity in response to osmotic
      stress were dissected. These include type, osmolality and concentration of
      solutes in the internal and/or external compartment (cationic, anionic,
      zwitterionic, neutral), as well as membrane strain as a response to increased
      osmolality. Osmoresponsive activation of BetP was independent of any external
      factor and of physical alterations of the membrane, but was triggered by a change
      in the internal K+ concentration. Activation did not depend on the type of anion
      present and was K+ (or Cs+ and Rb+) specific, as choline and NH(4)+ did not
      trigger BetP activity. The half-maximal activation of BetP in E.coli phospholipid
      liposomes was correlated to an internal concentration of 221 +/- 23 mM K+.

PMID- 11574474
TI  - A Drosophila MAPKKK, D-MEKK1, mediates stress responses through activation of p38
      MAPK.
AB  - In cultured mammalian cells, the p38 mitogen-activated protein kinase (MAPK)
      pathway is activated in response to a variety of environmental stresses. How
      ever, there is little evidence from in vivo studies to demonstrate a role for
      this pathway in the stress response. We identified a Drosophila MAPK kinase
      kinase (MAPKKK), D-MEKK1, which can activate p38 MAPK. D-MEKK1 is structurally
      similar to the mammalian MEKK4/MTK1 MAPKKK. D-MEKK1 kinase activity was activated
      in animals under conditions of high osmolarity. Drosophila mutants lacking D
      MEKK1 were hypersensitive to environmental stresses, including elevated
      temperature and increased osmolarity. In these D-MEKK1 mutants, activation of
      Drosophila p38 MAPK in response to stress was poor compared with activation in
      wild-type animals. These results suggest that D-MEKK1 regulation of the p38 MAPK
      pathway is critical for the response to environmental stresses in Drosophila.

PMID- 11574475
TI  - A completely foreign receptor can mediate an interferon-gamma-like response.
AB  - A tripartite receptor comprising the external region of the erythropoietin (Epo)
      receptor, the transmembrane and JAK-binding domains of the gp130 subunit of the
      interleukin-6 (IL-6) receptor, and a seven amino acid STAT1 recruitment motif
      (Y440) from the interferon (IFN)-gamma receptor, efficiently mediates an IFN
      gamma-like response. An analogous completely foreign chimeric receptor in which
      the Y440 motif is replaced with the Y905 motif from gp130 also mediates an IFN
      gamma-like response, but less efficiently. The IFNGR1 signal-transducing subunit
      of the IFN-gamma receptor is tyrosine phosphorylated through the chimeric
      receptors and the endogenous IL-6 and OSM receptors. Cross phosphorylation of
      IFNGR1 is not, however, required for the IFN-gamma-like response through the
      chimeric receptors, nor does it mediate an IFN-gamma-like response to IL-6 or
      OSM. The data argue strongly for modular JAK/STAT signalling and against any
      rigid structural organization for the "pathways" involved. They emphasize the
      likely high degree of overlap between the signals generated from disparate JAK
      receptor complexes and show that relatively minor changes in such complexes can
      profoundly affect the response.

PMID- 11574476
TI  - SMN interacts with a novel family of hnRNP and spliceosomal proteins.
AB  - Spinal muscular atrophy (SMA) is a common neurodegenerative disease caused by
      deletion or loss-of-function mutations of the survival of motor neurons (SMN)
      protein. SMN is in a complex with several proteins, including Gemin2, Gemin3 and
      Gemin4, and it plays important roles in small nuclear ribonucleoprotein (snRNP)
      biogenesis and in pre-mRNA splicing. Here, we characterize three new hnRNP
      proteins, collectively referred to as hnRNP Qs, which are derived from
      alternative splicing of a single gene. The hnRNP Q proteins interact with SMN,
      and the most common SMN mutant found in SMA patients is defective in its
      interactions with them. We further demonstrate that hnRNP Qs are required for
      efficient pre-mRNA splicing in vitro. The hnRNP Q proteins may provide a
      molecular link between the SMN complex and splicing.

PMID- 11574477
TI  - Design and development of a catalytic ribonucleoprotein.
AB  - Ribonucleoproteins (RNPs) consisting of derivatives of a ribozyme and an RNA
      binding protein were designed and constructed based upon high-resolution
      structures of the corresponding prototype molecules, the Tetrahymena group I self
      splicing intron RNA and two proteins (bacteriophage lambdaN and HIV Rev proteins)
      containing RNA-binding motifs. The splicing reaction proceeds efficiently only
      when the designed RNA associates with the designed protein either in vivo or in
      vitro. In vivo mutagenic protein selection was effective for improving the
      capability of the protein. Kinetic analyses indicate that the protein promotes
      RNA folding to establish an active conformation. The fact that the conversion of
      a ribozyme to an RNP can be accomplished by simple molecular design supports the
      RNA world hypothesis and suggests that a natural active RNP might have evolved
      readily from a ribozyme.

PMID- 11574478
TI  - Rapid formation of a solvent-inaccessible core in the Neurospora Varkud satellite
      ribozyme.
AB  - We have used hydroxyl radicals generated by decomposition of peroxynitrous acid
      to study Mg(2+)-dependent structure and folding of the Varkud satellite (VS)
      ribozyme. Protection from radical cleavage shows the existence of a solvent
      inaccessible core, which includes nucleotides near two three-helix junctions, the
      kissing interaction between stem-loops I and V and other nucleotides, most of
      which have also been implicated as important for folding or activity. Kinetic
      folding experiments showed that the ribozyme folds very quickly, with the
      observed protections completely formed within 2 s of addition of MgCl(2). In
      mutants that disrupt the kissing interaction or entirely remove stem-loop I,
      which contains the cleavage site, nucleotides in the three-helix junctions and a
      subset of those elsewhere remain protected. Unlike smaller ribozymes, the VS
      ribozyme retains a significant amount of structure in the absence of its
      substrate. Protections that depend on proper interaction between the substrate
      and the rest ribozyme map to a region previously proposed as the active site of
      the ribozyme and along both sides of helix II, identifying candidate sites of
      docking for the substrate helix.

PMID- 11574479
TI  - Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa
      Sm D1-like protein.
AB  - U7 snRNPs were isolated from HeLa cells by biochemical fractionation, followed by
      affinity purification with a biotinylated oligonucleotide complementary to U7
      snRNA. Purified U7 snRNPs lack the Sm proteins D1 and D2, but contain additional
      polypeptides of 14, 50 and 70 kDa. Microsequencing identified the 14 kDa
      polypeptide as a new Sm-like protein related to Sm D1 and D3. Like U7 snRNA, this
      protein, named Lsm10, is enriched in Cajal bodies of the cell nucleus. Its
      incorporation into U7 snRNPs is largely dictated by the special Sm binding site
      of U7 snRNA. This novel type of Sm complex, composed of both conventional Sm
      proteins and the Sm-like Lsm10, is most likely to be important for U7 snRNP
      function and subcellular localization.

PMID- 11574480
TI  - Box C/D small nucleolar RNA trafficking involves small nucleolar RNP proteins,
      nucleolar factors and a novel nuclear domain.
AB  - Nucleolar localization of box C/D small nucleolar (sno) RNAs requires the box C/D
      motif and, in vertebrates, involves transit through Cajal bodies (CB). We report
      that in yeast, overexpression of a box C/D reporter leads to a block in the
      localization pathway with snoRNA accumulation in a specific sub-nucleolar
      structure, the nucleolar body (NB). The human survival of motor neuron protein
      (SMN), a marker of gems/CB, specifically localizes to the NB when expressed in
      yeast, supporting similarities between these structures. Box C/D snoRNA
      accumulation in the NB was decreased by mutation of Srp40 and increased by
      mutation of Nsr1p, two related nucleolar proteins that are homologous to human
      Nopp140 and nucleolin, respectively. Box C/D snoRNAs also failed to accumulate in
      the NB, and became delocalized to the nucleoplasm, upon depletion of any of the
      core snoRNP proteins, Nop1p/fibrillarin, Snu13p, Nop56p and Nop5p/Nop58p. We
      conclude that snoRNP assembly occurs either in the nucleoplasm, or during transit
      of snoRNAs through the NB, followed by routing of the complete snoRNP to
      functional sites of ribosome synthesis.

PMID- 11574482
TI  - Escherichia coli DbpA is an RNA helicase that requires hairpin 92 of 23S rRNA.
AB  - Escherichia coli DbpA is a member of the DEAD/H family of proteins which has been
      shown to have robust ATPase activity only in the presence of a specific region of
      23S rRNA. A series of bimolecular RNA substrates were designed based on this
      activating region of rRNA and used to demonstrate that DbpA is also a non
      processive, sequence-specific RNA helicase. The high affinity of DbpA for the RNA
      substrates allowed both single and multiple turnover helicase assays to be
      performed. Helicase activity of DbpA is dependent on the presence of ATP or dATP,
      the sequence of the loop of hairpin 92 of 23S rRNA and the position of the
      substrate helix with respect to hairpin 92. This work indicates that certain RNA
      helicases require particular RNA structures in order for optimal unwinding
      activity to be observed.

PMID- 11574481
TI  - The major mRNA-associated protein YB-1 is a potent 5' cap-dependent mRNA
      stabilizer.
AB  - mRNA silencing and storage play an important role in gene expression under
      diverse circumstances, such as throughout early metazoan development and in
      response to many types of environmental stress. Here we demonstrate that the
      major mRNA-associated protein YB-1, also termed p50, is a potent cap-dependent
      mRNA stabilizer. YB-1 addition or overexpression dramatically increases mRNA
      stability in vitro and in vivo, whereas YB-1 depletion results in accelerated
      mRNA decay. The cold shock domain of YB-1 is responsible for the mRNA stabilizing
      activity, and a blocked mRNA 5' end is required for YB-1-mediated stabilization.
      Significantly, exogenously added YB-1 destabilizes the interaction of the cap
      binding protein, eIF4E, with the mRNA cap structure. Conversely, sequestration of
      eIF4E from the cap increases the association of endogenous YB-1 with mRNA at or
      near the cap, and significantly enhances mRNA stability. These data support a
      model whereby down-regulation of eIF4E activity or increasing the YB-1 mRNA
      binding activity or concentration in cells activates a general default pathway
      for mRNA stabilization.

PMID- 11574483
TI  - Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining
      chromosomal integrity in vertebrate cells.
AB  - Yeast Rad52 DNA-repair mutants exhibit pronounced radiation sensitivity and a
      defect in homologous re combination (HR), whereas vertebrate cells lacking Rad52
      exhibit a nearly normal phenotype. Bio chemical studies show that both yeast
      Rad52 and Rad55-57 (Rad51 paralogs) stimulate DNA-strand exchange mediated by
      Rad51. These findings raise the possibility that Rad51 paralogs may compensate
      for lack of Rad52 in vertebrate cells, explaining the absence of prominent
      phenotypes for Rad52-deficient cells. To test this hypothesis, using chicken DT40
      cells, we generated conditional mutants deficient in both RAD52 and XRCC3, which
      is one of the five vertebrate RAD51 paralogs. Surprisingly, the rad52 xrcc3
      double-mutant cells were non-viable and exhibited extensive chromosomal breaks,
      whereas rad52 and xrcc3 single mutants grew well. Our data reveal an overlapping
      (but non-reciprocal) role for Rad52 and XRCC3 in repairing DNA double-strand
      breaks. The present study shows that Rad52 can play an important role in HR
      repair by partially substituting for a Rad51 paralog.

PMID- 11574484
TI  - Structure and function of the N-terminal 40 kDa fragment of human PMS2: a
      monomeric GHL ATPase.
AB  - Human MutLalpha, a heterodimer of hMLH1 and hPMS2, is essential for DNA mismatch
      repair. Inactivation of the hmlh1 or hpms2 genes by mutation or epigenesis causes
      genomic instability and a predisposition to hereditary non-polyposis cancer. We
      report here the X-ray crystal structures of the conserved N-terminal 40 kDa
      fragment of hPMS2, NhPMS2, and its complexes with ATPgammaS and ADP at 1.95, 2.7
      and 2.7 A resolution, respectively. The NhPMS2 structures closely resemble the
      ATPase fragment of Escherichia coli MutL, which coordinates protein-protein
      interactions in mismatch repair by undergoing structural transformation upon
      binding of ATP. Unlike the E.coli MutL, whose ATPase activity requires protein
      dimerization, the monomeric form of NhPMS2 is active both in ATP hydrolysis and
      DNA binding. NhPMS2 is the first example of a GHL ATPase active as a monomer,
      suggesting that its activity may be modulated by hMLH1 in MutLalpha, and vice
      versa. The potential heterodimer interface revealed by crystallography provides a
      mutagenesis target for functional studies of MutLalpha.

PMID- 11574485
TI  - T-loop assembly in vitro involves binding of TRF2 near the 3' telomeric overhang.
AB  - Mammalian telomeres contain a duplex TTAGGG-repeat tract terminating in a 3'
      single-stranded overhang. TRF2 protein has been implicated in remodeling
      telomeres into duplex lariats, termed t-loops, in vitro and t-loops have been
      isolated from cells in vivo. To examine the features of the telomeric DNA
      essential for TRF2-promoted looping, model templates containing a 500 bp double
      stranded TTAGGG tract and ending in different single-stranded overhangs were
      constructed. As assayed by electron microscopy, looped molecules containing most
      of the telomeric tract are observed with TRF2 at the loop junction. A TTAGGG-3'
      overhang of at least six nucleotides is required for loop formation. Termini with
      5' overhangs, blunt ends or 3' termini with non-telomeric sequences at the
      junction are deficient in loop formation. Addition of non-telomeric sequences to
      the distal portion of a 3' overhang beginning with TTAGGG repeats only modestly
      diminishes looping. TRF2 preferentially localizes to the junction between the
      duplex repeats and the single-stranded overhang. Based on these findings we
      suggest a model for the mechanism by which TRF2 remodels telomeres into t-loops.

PMID- 11574486
TI  - Gamete donation and anonymity: disclosure to children conceived with donor
      gametes should not be optional.
AB  - The use of donor gametes in reproductive technology raises ethical, psychological
      and social questions that have been significant for the practice of adoption:
      that is, when, or if, to disclose biological origin to the child. The current
      wisdom is that adopted children should be told by their parents as early as
      possible that the family was created through adoption, and we argue that the same
      model should apply to the use of donor gametes. We argue that privacy concerns or
      other goals of parents who would prefer to avoid disclosure are outweighed by the
      negative consequences of holding such family secrets and by the child's right to,
      and medical need for, information about his/her origin. We believe fertility
      programmes and professional organizations ought to strongly encourage those using
      donor gametes to tell their child of their true origin as early as the child can
      understand reproduction in general.

PMID- 11574487
TI  - Gamete donation and anonymity: disclosure to children conceived with donor
      gametes should be optional.
AB  - To force potential parents to tell their child of his/her genetic origin as a
      requirement for admission into an infertility programme is both wrong and
      discriminatory. In addition, comparing the practice of using donor gametes to
      conceive a child with adoption is incorrect for a number of reasons. In this
      article we make the argument that mandatory disclosure is both inappropriate and
      intrusive, and the presently available data do not justify a rigid position.
      Furthermore, no reasonable, practical system can be envisaged to guarantee
      compliance with mandatory disclosure. Although it is entirely reasonable at the
      time of consultation to encourage couples to consider their positions and obtain
      a mutual agreement on their future intent prior to treatment, the final decision
      on this should be a matter of free choice within the context of the couple's own
      value system.

PMID- 11574488
TI  - Screening standards in assisted reproduction technologies: the screening of semen
      donors--where do we draw the line?
AB  - The most recent British Andrology Society guidelines have certainly stirred up
      much debate about the exclusion of donors that are seropositive for
      cytomegalovirus (CMV). Arguments will inevitably go back and forth regarding the
      statistical risk of donors passing on infection and the point at which that risk
      becomes unacceptable. As with many of these debates, a number of different
      opinions will be offered but a consensus will be almost impossible. However, the
      case of CMV highlights difficulties common to the screening of donors for many
      infectious and genetic disorders.

PMID- 11574489
TI  - Experimental inoculation of male mice with murine cytomegalovirus and effect on
      offspring.
AB  - BACKGROUND: Murine cytomegalovirus (MCMV) was used to examine aspects of viral
      infection in male mice, and its possible transmission to their offspring. METHODS
      AND RESULTS: FVB/N mice inoculated intratesticularly with 5x10(5) plaque forming
      units (PFU) of MCMV, developed peritoneal haemorrhagic exudates, spleen
      hypertrophy and acute local infection. Infectiousness was detected until 15 days
      post-inoculation (D15 PI) in the genital organs, and virus DNA up to D35 PI.
      Testicular endothelial and Leydig cells were infected, and peritubular cells
      severely damaged. Spermatogenesis was affected, but neither germ cells nor
      Sertoli cells were infected. No virus was found in the epididymal epithelial
      cells. Viral DNA was detected in cells extracted from vas deferens samples until
      D15 PI. Neither infectious virus nor viral DNA were found in spermatozoa
      recovered from uterine fluid, fertilized oocytes, blastocysts, fetal tissues or
      newborn animals following the mating of infected males with uninfected females.
      CONCLUSIONS: MCMV harboured in the male genital organs was not transmitted to
      their offspring, even when mating occurred during the acute phase of CMV disease.
      Although the infection may have had an impact on spermatogenesis, fertility was
      not affected. These results do not support the hypothesis of conceptus MCMV
      infection by the fertilizing spermatozoon in natural conception.

PMID- 11574490
TI  - The risk of endometriosis and exposure to dioxins and polychlorinated biphenyls:
      a case-control study of infertile women.
AB  - BACKGROUND: A case-control study was designed to determine the possible
      association between chronic exposure to dioxins and polychlorinated biphenyls
      (PCBs), and the occurrence of endometriosis. The study group consisted of 42
      infertile endometriosis cases and 27 mechanical infertile controls, both groups
      attending one of the collaborating Centres for Reproductive Medicine, enrolled
      between 1996-1998. METHODS: Exposure assessment to dioxin-like compounds was
      determined through CALUX (chemical-activated luciferase gene expression)-bioassay
      to measure dioxin-like total toxic equivalents (dioxins and co-planar PCBs),
      whereas non-co-planar PCBs were determined through chemical analysis. RESULTS: No
      association was found between median dioxin-like total toxic equivalents (TEQ)
      and the occurrence of endometriosis in infertile women [cases (n = 34): 29;
      controls (n = 27): 24; NS]. When patients were subdivided based on an arbitrary
      cut-off value of 100 pg TEQ/g serum lipids, no statistically significant
      association between very high exposure to dioxin-like compounds and endometriosis
      was found [crude odds ratio (OR) = 4.33; confidence interval (CI) 0.49-38.19;
      NS]. After adjusting for body mass index, and alcohol consumption, the risk
      increased slightly to OR = 4.6 (CI 0.48-43.62; NS). There was no confounding by
      age, ovulatory dysfunction, caffeine intake, smoking or exposure to non-co-planar
      PCBs. CONCLUSIONS: The study results showed no statistically significant
      association between exposure to dioxin-like compounds and the occurrence of
      endometriosis in infertile women.

PMID- 11574491
TI  - Ovarian tissue harvested from lymphoma patients to preserve fertility may be safe
      for autotransplantation.
AB  - BACKGROUND: Ovarian failure is a common sequel to chemo/radiotherapy in patients
      successfully treated for cancer. Harvesting, cryopreserving and subsequently re
      implanting ovarian cortical grafts can be used to re-establish reproductive
      potential in women with cancer. The safety issue, however, is of great concern
      because residual disease in autografted ovarian tissues might cause recrudescence
      of disease. METHODS: A total of 30 non-obese diabetic severe combined
      immunodeficient (NOD/LtSz-SCID) mice were individually xenografted s.c. with
      frozen-thawed ovarian tissue from 18 patients with lymphoma [13 Hodgkin's
      lymphoma (HL) and 5 non-Hodgkin's lymphoma (NHL)]. The animals were autopsied at
      16 weeks, or earlier if cachectic. The xenograft, liver, spleen, sternum, para
      aortic lymph nodes and thymus were prepared for histology, immunohistochemistry
      and human DNA microsatellite analysis. RESULTS: None of the animals grafted with
      ovarian tissue from lymphoma patients developed disease. However, all 3 animals
      grafted with lymph node tissue from an NHL patient developed B-cell lymphomas
      that were confirmed as human in origin by DNA microsatellite analysis.
      CONCLUSION: Ovarian tissue harvested before high-dose chemotherapy for HL or NHL
      may not carry a risk of disease transmission by autotransplantation, although the
      possibility is difficult to exclude completely.

PMID- 11574492
TI  - Effects of androstenedione, insulin and luteinizing hormone on steroidogenesis in
      human granulosa luteal cells.
AB  - BACKGROUND: The present study was conducted to investigate the effect of
      androstenedione, insulin and LH on human granulosa cell oestrogen and
      progesterone production. We postulated that elevated concentrations of
      androstenedione, insulin and LH may be important modulators of granulosa cell
      steroidogenesis. METHODS: Granulosa cells obtained in connection with IVF
      procedures were cultured for a total of 4 days in serum-free medium containing
      androstenedione (10(-6) mol/l). We tested the effect of androstenedione (10(-5)
      mol/l) on insulin (0-800 microIU/ml), LH (1-10 ng/ml) as well as on insulin + LH
      stimulated oestrogen and progesterone production. RESULTS: Insulin increased the
      basal secretion of steroid hormones, and furthermore augmented LH-stimulated
      oestrogen and progesterone accumulation in granulosa cell cultures.
      Androstenedione (10(-5) mol/l) stimulated basal oestrogen production, but
      significantly reduced (32-58%) insulin + LH-stimulated oestrogen and progesterone
      secretion (P < 0.05). CONCLUSION: These results suggest that high androstenedione
      concentrations may act directly to impair insulin augmentation of LH-stimulated
      oestradiol and progesterone production in cultured human granulosa luteal cells.
      This is compatible with the hypothesis that high androgen levels may inhibit
      oestrogen production in polycystic ovary follicles, and as such may contribute to
      anovulation and infertility in women with polycystic ovary syndrome.

PMID- 11574493
TI  - Clinical, endocrine and metabolic effects of acarbose, an alpha-glucosidase
      inhibitor, in PCOS patients with increased insulin response and normal glucose
      tolerance.
AB  - BACKGROUND: The aim of this study was to evaluate whether treatment with
      acarbose, an alpha-glucosidase inhibitor, improved hyperandrogenic symptoms,
      insulin and androgen serum concentrations in hyperinsulinaemic patients with
      polycystic ovary syndrome (PCOS). METHODS: 30 hyperinsulinaemic women with PCOS
      and 15 controls were evaluated. Patients were randomized, using a computer
      generated randomization list, into two groups of 15 each and treated with placebo
      or 300 mg/day of acarbose for three months. Hirsutism and acne/seborrhoea scores,
      hormonal and sex hormone binding globulin serum concentrations, glycaemia and
      insulin responses to a standard oral glucose load (75g) were measured in all
      patients before and after three months of treatment. RESULTS: A significant
      reduction of the acne/seborrhoea score was observed in patients treated with
      acarbose and eight of them resumed a regular menstrual rhythm. These clinical
      improvements were associated with a significant reduction of the insulin response
      to glucose load, a significant decrease of LH, total testosterone and
      androstenedione and with a significant increase of sex hormone binding globulin
      serum concentrations. The serum concentrations of FSH, dehydroepiandrosterone
      sulphate, prolactin and 17alpha-hydroxyprogesterone did not change significantly.
      No clinical, metabolic and hormonal modifications were observed in PCOS patients
      treated with placebo. CONCLUSIONS: This is the first report showing a reduction
      of the acne/seborrhoea score in hyperinsulinaemic patients with PCOS treated with
      acarbose. This improvement was associated with a significant decrease of the
      insulin response to oral glucose load and of LH and androgen serum concentrations
      and with a significant rise of sex hormone binding globulin concentration.

PMID- 11574494
TI  - Follicular fluid concentration of leukaemia inhibitory factor is decreased among
      women with polycystic ovarian syndrome during assisted reproduction cycles.
AB  - BACKGROUND: The possibility that a specific cytokine profile could be detected in
      the ovaries of patients with polycystic ovarian syndrome (PCOS) was investigated.
      METHOD: Enzyme-linked immunosorbent assay (ELISA) or bioassays were used to
      assess the concentrations of leukaemia inhibitory factor (LIF), tumour necrosis
      factor, interleukin 11, gamma interferon, progesterone and oestradiol in
      follicular fluids from preovulatory follicles collected after ovarian stimulation
      from 15 PCOS patients, 15 infertile control patients with regular cycles, and 8
      oocyte donors. RESULTS: LIF and progesterone concentrations were significantly
      lower in the follicular fluid of PCOS patients (LIF median: 265 pg/ml) compared
      with controls (LIF median: 816 pg/ml); LIF and progesterone follicular fluid
      concentrations were correlated (r = 0.720, P = 0.0001). The LH/FSH ratio was
      negatively correlated with LIF concentrations (r = - 0.714, P = 0.0075). Although
      the PCOS and control patients did not differ significantly in age, ovarian
      reserve or IVF indication, the implantation rate was significantly lower among
      the women with PCOS (IR = 9 versus 21%, P = < 0.01). CONCLUSION: The specific
      cytokine profile of the PCOS patients is probably related to the lower
      implantation rate since follicular fluid LIF appears to function as an
      embryotrophic agent.

PMID- 11574495
TI  - Basal and day 12 inhibin concentrations in the prediction of ovarian response to
      gonadotrophins in women with PCOS.
AB  - BACKGROUND: In this study, we aimed to investigate whether basal and day 12 serum
      total inhibin concentrations in women with polycystic ovarian syndrome (PCOS)
      were of predictive value for the estimation of the ovarian response to
      gonadotrophins. METHODS: Ovulation induction with a very low dose gonadotrophin
      protocol, starting with 37.5 IU/day, was performed for 40 cycles on 35 patients
      with PCOS. Day 3 (basal) serum total inhibin, FSH and oestradiol concentrations;
      day 12 dominant follicle diameter, inhibin and oestradiol concentrations and
      midluteal serum progesterone concentrations were measured during the 40 cycles.
      The correlations between basal and day 12 inhibin concentrations and some
      critical ovulation monitoring parameters were investigated. RESULTS: Ovulation
      was obtained in 14 out of 40 cycles: 21% of cycles with basal inhibin <1.0 IU/ml;
      33.3% of cycles with basal inhibin between 1.0-1.9 IU/ml; and 83.3% of those with
      inhibin concentrations > or =2 IU/ml were ovulatory (P < 0.05). Ovulation was
      achieved in 91.6% of the cycles with a day 12 inhibin concentration > or =4
      IU/ml. CONCLUSIONS: Basal inhibin concentrations may determine poor and good
      responders to ovulation induction with very low dose gonadotrophin protocol in
      patients with PCOS. The day 12 inhibin concentration was found to be a more
      sensitive parameter than the oestradiol concentration in the prediction of
      follicular maturation.

PMID- 11574496
TI  - Incidence of sperm chromosomal abnormalities in a risk population: relationship
      with sperm quality and ICSI outcome.
AB  - BACKGROUND: An increased incidence of chromosome abnormalities has been reported
      in sperm samples of many infertile men by fluorescence in-situ hybridization
      (FISH). METHODS: Sperm aneuploidy and diploidy rates for chromosomes 13, 18, 21,
      X and Y were evaluated in 63 patients with normal karyotypes using dual and
      triple-colour FISH techniques. Indications for sperm FISH analysis were:
      recurrent miscarriages of unknown aetiology (RM, n = 40), repeated implantation
      failure after intracytoplasmic sperm injection (ICSI) (IF, n = 19), previous
      Down's syndrome pregnancies (n = 3), and meiotic abnormalities (MA, n = 1). Nine
      healthy normozoospermic donors were also evaluated as a control group. RESULTS: A
      significant increase in the incidence of sex chromosome disomies was found in the
      RM, IF and MA groups. Oligoasthenoteratozoospermic patients (n = 21) showed
      significantly higher rates of diploidy and disomies for sex chromosomes and
      chromosomes 18 and 21 than normozoospermic patients (n = 14). Thirty-one patients
      with normal and seven with abnormal FISH results had undergone several ICSI
      treatments (108 and 23 cycles respectively). Couples with abnormal sperm FISH
      results showed decreased pregnancy and implantation rates and increased
      miscarriage rates. CONCLUSIONS: Patients with a clinical background of recurrent
      miscarriages of unknown aetiology or implantation failure after ICSI are at risk
      of showing sperm chromosomal abnormalities, the incidence of which is higher in
      oligoasthenoteratozoospermic patients.

PMID- 11574497
TI  - Cystic fibrosis phenotype evaluation and paternity outcome in 50 males with
      congenital bilateral absence of vas deferens.
AB  - BACKGROUND: Most infertile males with congenital bilateral absence of vas
      deferens (CBAVD) carry mutations on the cystic fibrosis transmembrane conductance
      regulator gene and may express mild cystic fibrosis (CF) symptoms. Barriers to
      paternity for these men can now be overcome by assisted reproduction. Our aims
      were to investigate the CF-related phenotype and clinical outcome for 50 patients
      with CBAVD seen at a CF adult centre between 1992 and 1999. METHODS AND RESULTS:
      The investigation of the patients included screening for 22 CF mutations and
      identification of the poly-T variant of intron 8, sweat testing, clinical
      investigation for CF-related extra-genital manifestations, and genetic
      counselling. CFTR mutations were detected on 56 alleles of the 50 patients. A
      total of 15 (30%) was compound heterozygote and 26 (52%) heterozygote. In all,
      38% of the patients had a positive sweat test. Four patients were diagnosed with
      typical CF not detected previously. Twenty-one patients became fathers following
      ICSI (eight cases), artificial insemination by donor or IVF with sperm donor
      (seven cases) or through adoption (six cases). A mail survey allowed the
      identification of CF-related clinical symptoms. Information on the occurrence of
      CF-related symptoms was obtained for 58.5% of patients: in the absence of initial
      symptoms, no new clinical signs were reported. CONCLUSION: Patients diagnosed
      with CBAVD need genetic counselling before assisted reproduction. Even when no
      wish for paternity is expressed, CF gene screening should be associated with at
      least a sweat test and clinical evaluation because of possible mild forms of CF
      disease. Medical follow-up did not reveal any new symptoms.

PMID- 11574498
TI  - Double-blind randomized trial of mifepristone in combination with vaginal
      gemeprost or misoprostol for induction of abortion up to 63 days gestation.
AB  - BACKGROUND: Gemeprost and misoprostol are two of the most widely used
      prostaglandins in combination with mifepristone for medical abortion in early
      pregnancy. However, the efficacy and side-effects of those two drugs given
      vaginally have not been assessed in a randomized trial. METHODS: Randomized
      double-blind controlled trial involving 999 women undergoing an abortion at
      gestational age < or =63 days who received either 0.5 mg gemeprost (group I, n =
      499) or 800 microg misoprostol (group II, n = 500) vaginally approximately 48 h
      after taking 200 mg mifepristone by mouth. The rate of complete abortion and the
      side-effects were compared between the groups. RESULTS: A total of 89 cases was
      excluded from full analysis of outcome because either they aborted after
      mifepristone alone (n = 2), had an ectopic pregnancy (n = 1), or because the
      outcome was uncertain as they failed to attend their follow-up appointment (n =
      86). The rate of complete abortion was very high (>95%) in both groups but
      significantly higher after treatment with misoprostol than with gemeprost
      [436/453 (98.7%) versus 451/457 (96.2%), P = 0.019, difference 2.5%, confidence
      interval 0.4-4.7%] and there were fewer ongoing pregnancies (n = 1 versus n = 8,
      P < 0.018). Surgical intervention rose significantly with gestation in women who
      received gemeprost (P < 0.03) but not with misoprostol. The incidence of side
      effects such as diarrhoea (13.7 versus 16.4%) and vomiting (27.8 versus 29.7%)
      was similar in women who received misoprostol or gemeprost respectively, as was
      the duration and amount of bleeding. CONCLUSIONS: (i) Both regimens using a
      reduced dose of mifepristone are highly effective methods of inducing abortion in
      early pregnancy; (ii) vaginal misoprostol is the preferred prostaglandin because
      it is it is associated with fewer failures than low-dose gemeprost, particularly
      at gestation > or =49 days.

PMID- 11574499
TI  - Effects of the levonorgestrel-releasing intrauterine system on proliferation and
      apoptosis in the endometrium.
AB  - BACKGROUND: The levonorgestrel-releasing intrauterine system (LNg-IUS) has been
      shown to be effective in the management of menorrhagia. In order to evaluate the
      effects of LNg-IUS on endometrial proliferation and apoptosis, proliferating cell
      nuclear antigen (PCNA) expression, apoptosis, Fas and Bcl-2 protein expression in
      the endometrium were determined at the early proliferative phase of the menstrual
      cycle before and 3 months after LNg-IUS insertion. METHODS: PCNA, Fas and Bcl-2
      protein expression were analysed using an avidin-biotin immunoperoxidase method.
      Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated
      deoxy-UTP nick-end labelling (TUNEL) method. RESULTS: PCNA, immunolocalized both
      in the nuclei of endometrial glands and stroma was less abundant 3 months after
      insertion (P < 0.05). Bcl-2 protein, immunolocalized in the cytoplasm of
      endometrial glands but not in the stroma, became scanty 3 months after insertion.
      Fas antigen, immunolocalized only in endometrial glands before insertion, became
      prominent in both endometrial glands and stroma 3 months after insertion. The
      apoptosis-positive rate of the nuclei in both endometrial glands and stroma was
      significantly higher 3 months after insertion relative to that before insertion
      (P < 0.05). CONCLUSIONS: LNg-IUS resulted in a decrease in endometrial
      proliferation and an increase in apoptosis in endometrial glands and stroma. The
      increase in apoptosis associated with increased Fas antigen expression and
      decreased Bcl-2 protein expression in the endometrium may be one of the
      underlying molecular mechanisms by which LNg-IUS insertion causes the atrophic
      change of the endometrium.

PMID- 11574500
TI  - The outcome of intracytoplasmic injection of fresh and cryopreserved ejaculated
      spermatozoa--a prospective randomized study.
AB  - BACKGROUND: The overall aim of this prospective, randomized study was to compare
      the reproductive potential of fresh and frozen-thawed ejaculated spermatozoa from
      oligoasthenoteratozoospermic patients in an intracytoplasmic sperm injection
      (ICSI) procedure. METHODS: All patients consenting to participate in this study
      had a sperm sample frozen prior to the start of a cycle. Patients were randomized
      using a random number table to undergo ICSI with either fresh (group A, n = 118)
      or frozen-thawed (group B, n = 122) spermatozoa. All prognostic variables were
      equally distributed among the two groups. RESULTS: The pregnancy rate per started
      cycle was 29.7% in group A and 38.5% in group B, P > 0.05. A significant
      difference was observed in the rate of ongoing pregnancies between group A
      (23.7%) and group B (35.2%), P < 0.05. CONCLUSION: From our data we can conclude
      that cryopreservation of spermatozoa from men with poor sperm quality does not
      negatively affect fertilization and pregnancy rates after ICSI. A larger study
      will be needed to investigate whether the use of cryopreserved spermatozoa can be
      helpful in selecting the most vital spermatozoa for ICSI.

PMID- 11574501
TI  - Colour Doppler analysis of peri-implantation utero-ovarian haemodynamics in women
      with excessively high oestradiol concentrations after ovarian stimulation.
AB  - BACKGROUND: Gonadotrophins are used in many assisted reproduction units to
      achieve a better success rate by increasing the number of replaced embryos.
      However, high oestradiol concentrations are associated with altered physiological
      functions and its complications. We investigated whether high oestradiol
      concentrations (> or =20 000 pmol/l) after ovarian stimulation in infertile women
      would affect the uterine haemodynamics at the time of embryo transfer. METHODS:
      Colour Doppler indices of utero-ovarian arteries and endometrial colour signals
      were measured. Fifty-eight women undergoing ovarian stimulation for IVF were
      classified according to serum oestradiol concentrations on the day of human
      chorionic gonadotrophin injection into moderate responders (oestradiol <20 000
      pmol/l; n = 39) and high responders (oestradiol > or =20 000 pmol/l; n = 19).
      RESULTS: Haemodynamic parameters were significantly lower in high responders; the
      uterine arterial pulsatility index (PI) and resistance index (RI) were (median;
      range) 1.87 (0.84-2.82) and 0.79 (0.57-0.90) respectively; ovarian artery PI was
      0.57 (0.40-1.12) and RI was 0.43 (0.33-0.64). In moderate responders the uterine
      PI and RI were 2.63 (1.46-5.92) and 0.88 (0.77-1.10) respectively. Ovarian PI was
      0.81 (0.32-3.72) and RI was 0.55 (0.23-0.97). The number of women showing
      endometrial colour signals was significantly lower in high responders (63%) than
      in moderate responders (92%) (P < 0.05). A further increase in oestradiol (> or
      =25 000 pmol/l; n = 8) showed significantly (P = 0.03) fewer endometrial colour
      signals [1.5 (0-8)] compared with moderate responders [4 (0-14)]. CONCLUSION:
      Despite low uterine PI and RI, the endometrial blood flow in high responders
      appears to be impaired. This may contribute to the decline in implantation
      efficiency noted in high responders.

PMID- 11574502
TI  - Tracking of oocyte dysmorphisms for ICSI patients may prove relevant to the
      outcome in subsequent patient cycles.
AB  - BACKGROUND: We determined whether oocyte dysmorphisms, especially repetition of
      specific dysmorphisms from cycle to cycle, had a prognostic impact on
      intracytoplasmic sperm injection (ICSI) outcome. METHODS: ICSI patients (n = 67)
      were grouped as follows: group 1 >50% phenotypically dysmorphic oocytes per
      cohort (cytoplasmic and extra-cytoplasmic dysmorphisms) with no repetition of a
      specific dysmorphism from cycle one to cycle two (36 cycles and 274 oocytes);
      group 2 >50% dysmorphic oocytes per cohort and repetition of the same dysmorphism
      from cycle one to cycle two (32 cycles and 313 oocytes); group 3 (control) <30%
      dysmorphic oocytes (33 cycles and 378 oocytes). RESULTS: In group 2 (repetitive),
      47% of oocytes were observed to have organelle clustering versus 20.5% in group 1
      and 17.3% in group 3 (P < 0.001). There was no difference between the groups in
      fertilization rates, cleavage rates or embryo quality. Embryos derived from
      normal oocytes were transferred in each group (57, 33 and 72% respectively). The
      clinical pregnancy and implantation rates in group 2 (3.1 and 1.7% respectively)
      were lower (P < 0.01, P = 0.005) than both group 1 (28 and 15% respectively) and
      group 3 (45.5 and 26.5% respectively). CONCLUSIONS: The low implantation rate in
      group 2, even though 33% of transferred embryos were derived from morphologically
      normal oocytes, suggests that repetitive organelle clustering may be associated
      with an underlying adverse factor affecting the entire follicular cohort.

PMID- 11574503
TI  - Risk factors for high-order multiple implantation after ovarian stimulation with
      gonadotrophins: evidence from a large series of 1878 consecutive pregnancies in a
      single centre.
AB  - BACKGROUND: High-order multiple pregnancies (triplets or more) have a large
      adverse impact on perinatal morbidity and mortality as well as important economic
      consequences. Most triplets and higher births are due to ovulation induction
      alone or in combination with intrauterine insemination (IUI) rather than to in
      vitro fertilization (IVF). The present investigation was undertaken to determine
      whether there were specific variables that related to patient clinical
      characteristics (age of the woman, duration of infertility, type of infertility,
      body mass index, basal FSH and LH concentrations), treatment characteristics
      (initial dose of gonadotrophins, total dose of gonadotrophins administered,
      number of days of ovarian stimulation, insemination procedure, number of
      spermatozoa inseminated in patients undergoing IUI, type of luteal support), and
      ovarian response (oestradiol serum concentrations, number and size of follicles)
      that might be associated with the occurrence of high-order multiple implantation
      in order to develop a prediction model. METHODS: This study employed univariate,
      multivariate and receiver-operating characteristic (ROC) analysis of a large
      series of 1878 consecutive pregnancies obtained in cycles stimulated with
      gonadotrophins. Of them, 1771 (94.3%) were low-order pregnancies (1477 singletons
      and 294 pairs of twins) and 107 (5.7%) were high-order pregnancies. RESULTS:
      Predictive variables in the multivariate analysis were age of the woman, serum
      oestradiol concentrations and number of follicles >10 mm on the day of HCG
      injection. Stratification of the number of follicles into three categories (1 to
      3, 4 to 5, and >5 follicles respectively), peak serum oestradiol and woman's age
      according to the ROC curves, showed that the risk of high-order multiple
      implantation correlated significantly with increasing total number of follicles
      and was significantly increased in women with a serum oestradiol >862 pg/ml and
      aged < or =32 years. CONCLUSIONS: This three-variable model can help to identify
      patients at high-risk for high-order multiple pregnancy in ovulation induction
      cycles.

PMID- 11574504
TI  - Immunological testing and treatment in reproduction: frequency assessment of
      practice patterns at assisted reproduction clinics in the USA and Australia.
AB  - BACKGROUND: The roles that alloimmunity and autoimmunity may play in reproductive
      failure, including recurrent pregnancy loss and failed IVF, have not been clearly
      established. To help define practice patterns, we investigated what tests
      clinicians in the USA and Australia were offering, to which patients (diagnostic
      groups) the tests were recommended, and in what situations
      immunological/anticoagulation treatment was advised. METHODS: A five section
      survey was completed by senior physicians attending the annual national fertility
      society meetings in the USA and Australia. Results were tabulated and analysed.
      RESULTS: Antiphospholipid antibody testing was offered to patients with recurrent
      pregnancy loss by almost all physicians surveyed. Patients with previous failure
      of IVF were tested much less often. Other immune tests (embryotoxic assay,
      natural killer cells and leukocyte antibodies) were ordered by none of the
      Australian participants and approximately 25% of the American participants. The
      use of immunotherapy and anticoagulation therapy for patients who tested positive
      for various immunological tests was also evaluated for frequency of use and
      reported secondary complications. CONCLUSIONS: Large, well-structured studies
      examining the benefits of immunological evaluation and treatment are necessary
      before definite recommendations can be made.

PMID- 11574505
TI  - An idiopathic infertility with oocytes metaphase I maturation block: case report.
AB  - BACKGROUND: A case of idiopathic primary infertility was attributed to a block in
      oocyte meiosis affecting the transition between metaphase I and metaphase II.
      METHODS AND RESULTS: A couple suffering unexplained primary infertility was
      unsuccessfully treated by various means of assisted reproductive technology.
      After four unsuccessful pregnancy attempts using intrauterine inseminations
      (IUI), IVF was attempted (all oocytes remained unfertilized), followed by an ICSI
      cycle. None of the retrieved oocytes expelled the polar body, and therefore were
      not injected. The failure of these assisted reproduction cycles was, in both
      cases, due to the immaturity of the oocytes recovered. Cytogenetic analysis of
      the oocytes retrieved for ICSI provided evidence of meiotic arrest. Using
      cytogenetic staging criteria we were able to show that this arrest occurred
      between metaphase I and anaphase I. CONCLUSIONS: Meiotic blocks affecting oocytes
      have already been described for various mammals. We discuss here mechanisms that
      might be involved in this possibly inherited disorder in humans, and ways in
      which our knowledge of them could be increased.

PMID- 11574506
TI  - Cryopreservation-induced acrosomal vesiculation in live spermatozoa from
      cynomolgus monkeys (Macaca fascicularis).
AB  - BACKGROUND: Cryopreserved spermatozoa are known to undergo accelerated
      capacitation and require a shorter incubation time for fertilization. However,
      details of their acrosomal membranes following cryopreservation remain unclear.
      METHODS: Percoll density gradient centrifugation was used to remove dead
      spermatozoa; thus >90% live spermatozoa were recovered after cryopreservation,
      and acrosomal status was compared among non-incubated and incubated fresh and
      cryopreserved spermatozoa. RESULTS: Transmission election microscopy (TEM) using
      microwave methods and fluorescein isothiocyanate-conjugated Pisum sativum
      agglutinin (FITC-PSA) staining revealed that 21.1 and 61.6% respectively of non
      incubated, cryopreserved spermatozoa were intact, whereas 97.6% (TEM) or 91.9%
      (FITC-PSA) of non-incubated fresh spermatozoa were intact. TEM revealed that
      28.8% of the cryopreserved spermatozoa were swollen, and probably included among
      those counted as intact by FITC-PSA staining. The non-incubated cryopreserved
      spermatozoa had fused plasma and outer acrosomal membranes, and 36.4% of them had
      vesiculation when observed by TEM. FITC-PSA staining indicated that 22% of the
      live spermatozoa were acrosome reacted. CONCLUSIONS: Acceleration of the acrosome
      reaction was evident by both TEM and FITC-PSA. Incubation of cryopreserved
      spermatozoa for 2 h accelerated vesiculation to a state similar to that of fresh
      spermatozoa that had been incubated for 8 h. These results reveal that in
      cryopreserved spermatozoa, the process of acrosome reaction begins before
      incubation.

PMID- 11574507
TI  - Cryopreservation of fractionated, highly motile human spermatozoa: effect on
      membrane phosphatidylserine externalization and lipid peroxidation.
AB  - INTRODUCTION: This study investigated lipid peroxidation (LPO) and membrane
      integrity following cryopreservation-thawing. METHODS: Infertile men (study
      group) and donors (control group) were examined. Purified populations of highly
      motile spermatozoa were cryopreserved using TEST-yolk buffer and glycerol (TYB-G)
      followed by quick thaw. LPO was measured by a spectrophotometric assay, with and
      without a ferrous ion promoter. Annexin V binding was used to assess membrane
      translocation of phosphatidylserine (PS). RESULTS: Pre-freeze LPO was
      significantly higher in the study than in the control group (P = 0.03). In both
      groups, LPO measurements after thawing were significantly higher than the pre
      freeze samples not exposed to TYB-G (P = 0.002 and P = 0.001 respectively).
      However, when the pre-freeze samples with TYB-G were compared with the post-thaw
      samples (all exposed to TYB-G), these differences were not significant. There was
      a significant increase in PS externalization following cryopreservation in both
      groups (P = 0.02 and P = 0.003 respectively). In donors, pre-freeze LPO
      concentrations had a significant positive correlation with thawed spermatozoa
      depicting PS externalization (r = 0.77, P = 0.04). CONCLUSION: Although patients
      had higher basal LPO than donors, LPO did not differ between fresh and
      cryopreserved-thawed fractionated motile spermatozoa. Freezing-thawing was
      associated with translocation of PS to the external membrane leaflet.

PMID- 11574508
TI  - Percutaneous cutting needle biopsies for histopathological assessment and sperm
      retrieval in men with azoospermia.
AB  - BACKGROUND: Twenty-three men (45 testes) with azoospermia underwent percutaneous
      testicular biopsy under local anaesthesia. METHODS: In all but one of the 45
      testes two biopsies were taken close to each other, one with a 16 gauge (n = 44)
      and another with a 14 gauge (n = 45) cutting needle, both with a 19 mm notch.
      Three quarters of the tissue was used for histopathological assessment and one
      quarter for direct microscopy. RESULTS: The histopathological findings were
      similar between the two needles. The observations with direct microscopy
      corresponded with the histopathological assessments concerning the presence of
      mature spermatids in 41 of 45 (91%) biopsies using the 14 gauge and in 40 of 44
      (91%) biopsies using the 16 gauge needle. There were no post-operative
      complications except for minimal pain and minor local swelling. CONCLUSIONS:
      Percutaneous material retrieved using 16 gauge and 14 gauge needles is sufficient
      for histopathological assessment, and the two needles are equally reliable for
      testicular sperm retrieval. However, needle biopsy with one puncture may not be
      representative of the entire testis.

PMID- 11574509
TI  - Interrelationships between seminal parameters and sperm nuclear DNA damage before
      and after density gradient centrifugation: implications for assisted conception.
AB  - BACKGROUND: With an increase in the use of assisted reproduction technologies the
      requirements of the diagnostic semen analysis are constantly changing. METHODS:
      Spermatozoa from patients undergoing IVF were analysed by examining the
      conventional semen parameters and DNA/chromatin integrity, using in-situ nick
      translation (NT) and the Chromomycin A(3) fluorochrome, which indirectly
      demonstrates a decreased presence of protamine. Samples were examined before and
      after preparation using discontinuous density gradient centrifugation. RESULTS:
      Density gradient centrifugation enriched samples by improving the percentage of
      morphologically normal forms by 138% and sperm nuclear integrity by 450%. Sperm
      nuclear integrity as assessed by in-situ nick translation (NT) demonstrated a
      very clear relationship with sperm concentration, motility and morphology.
      Morphology correlated with fertilization rates of patients undergoing IVF, while
      NT values of the spermatozoa post-preparation were significantly lower in
      pregnant patients. CONCLUSIONS: We have demonstrated that along with the
      classical semen parameters, the assessment of nuclear integrity improves the
      characterization of the semen sample and may be used as a tool for allocating
      patients to specific assisted reproduction treatments.

PMID- 11574510
TI  - The impact of the zona pellucida thickness variation of human embryos on
      pregnancy outcome in relation to suboptimal embryo development. A prospective
      randomized controlled study.
AB  - BACKGROUND: The study represents a prospective randomized controlled study
      evaluating zona pellucida thickness variation (ZPTV) measurements versus
      conventional selection of embryos using classic embryo score criteria, prior to
      embryo transfer in human IVF/intracytoplasmatic sperm injection (ICSI). METHODS:
      Eighty-six patients having > or =3 embryos, with a classic embryo score of < or
      =2.2, were allocated to either ZPTV measurement or classic embryo morphology
      score before embryo transfer. The technician selecting embryos using classic
      embryo scoring was not aware of the ZPTV measurement results. Of the embryos
      allocated to ZPTV measurements, only the embryos with the highest ZPTV were
      transferred. RESULTS: We found no differences in the pregnancy rate per embryo
      transfer between the two groups (34.4 versus 35.7%). Neither did the implantation
      rates differ. However, significantly better results were obtained when ZPTV was
      used as the selection criteria in cases where all embryos had an asynchrony in
      development or a high embryo score (i.e. were of poorer quality) by classical
      evaluation (odds ratio = 2.51, confidence interval = 0.33-198). CONCLUSIONS:
      Using a normally-developed embryo with an optimal embryo score, no beneficial
      effect of using ZPTV measurement was seen. However, when only less optimal
      embryos were available to select for transfer, ZPTV provided a x 2.5 increase in
      the chance of achieving a clinical pregnancy.

PMID- 11574511
TI  - Effect of retinoic acid on implantation and post-implantation development of
      mouse embryos in vitro.
AB  - BACKGROUND: This study was designed to examine the embryotoxic potential of
      retinoic acid (RA) at the blastocyst stage and during early post-implantation
      development of mouse embryos in vitro. METHODS AND RESULTS: All-trans retinoic
      acid (t-RA) was administered to ICR mice embryos at a dose level of 0, 0.001
      micromol/l, 0.1 micromol/l and 10 micromol/l throughout in-vitro culture. A total
      of 404 embryos was randomly assigned to all different dose groups. The percentage
      of embryos in later stages of development changed depending upon the dose of RA
      used. Exposure to 10 micromol/l of t-RA at the blastocyst stage, implanted
      blastocyst stage or early oocyte stage was also found to cause different degrees
      of retardation of embryo development and embryo death. These findings
      demonstrate, for the first time, that RA exerts an adverse effect on embryo
      growth during the early post-implantation stages of development, in comparison
      with day 3 to day 8 of gestation in vivo. CONCLUSIONS: Although isotretinoin (13
      cis-retinoic acid) is effective for the therapy of cystic acne and other
      dermatological disorders, retinoid treatment should be avoided at the early post
      implantation stage of gestation.

PMID- 11574512
TI  - The predictive value of pronuclear morphology of zygotes in the assessment of
      human embryo quality.
AB  - BACKGROUND: Recent studies have shown that zygote morphology could be used for
      the assessment of human embryo quality. Pronuclear (PN) morphology is based on
      certain distinct features seen in zygotes 16-18 h after fertilization. In the
      present study PN stage morphology was assessed and combined with a single embryo
      transfer in order to investigate whether currently used zygote classifications
      are able to predict embryo quality and implantation rates. METHODS AND RESULTS:
      Zygotes were analysed according to two different classification systems. In the
      first, a total of 764 zygotes was analysed according to the degree of
      polarization of nucleolar precursor bodies (NPB). Zygotes with unpolarized PN
      (i.e. scattered localization of NPB) showed significantly slower (P < 0.005)
      cleavage rates (38.9%) than zygotes having at least one pronucleus polarized
      (57.3% and 54%). However, there was no difference in the pregnancy rate in 105
      single embryo transfers between the groups. The appearance of a cytoplasmic halo
      was related to embryo morphology. Embryos derived from halo-positive zygotes had
      significantly better (P < 0.05) morphology (60.9%) compared to halo-negative
      derived embryos (52.2%), but in terms of pregnancy rates no difference was found.
      A total of 1520 zygotes was analysed according to a second classification system,
      which was based on the number and distribution of NPB. In the comparative
      analysis, none of the six different classes produced superior quality embryos or
      higher pregnancy rates in 144 single embryo transfers. CONCLUSIONS: Our results
      indicate that there are no significant differences in embryo quality or
      implantation/pregnancy rates between proposed zygote classes.

PMID- 11574513
TI  - A comparison between quarter, partial and total laser assisted hatching in
      selected infertility patients.
AB  - BACKGROUND: The object of this study was to evaluate the efficacy of laser
      assisted hatching (LAH) of embryos on implantation and pregnancy rates of a
      selected group of infertility patients. METHODS: A total of 322 cycles using LAH
      was undertaken in our Centre between June 1998 and September 1999. Patients were
      offered LAH if they fell in either one or more of the following categories: (i)
      Patients over 37 years of age undergoing either IVF or intracytoplasmic sperm
      injection (ICSI) treatment cycles; (ii) patients with more than 2 previous
      treatment cycle failures; (iii) patients undergoing frozen embryo replacement
      cycles and (iv) women who were considered to be poor responders. The initial
      results of totally breaching the zona pellucida (total LAH; group 1) did not meet
      with our expectations. We subsequently modified the technique to thinning one
      area of the zona pellucida (partial LAH; group 2) and this thinned area was then
      extended to a quarter segment (quarter LAH; group 3). RESULTS: In group 1, the
      pregnancy rate was 14.6% with a clinical pregnancy rate of 5.2%. In group 2 the
      pregnancy rate was 20.9% with a clinical pregnancy rate of 18% and for patients
      in group 3 the pregnancy rate was 29.0% with a clinical pregnancy rate of 22.1%.
      CONCLUSIONS: Overall there was firm statistical evidence that the pregnancy and
      clinical pregnancy rates arising from quarter LAH were higher in comparison with
      partial and total LAH.

PMID- 11574514
TI  - Effective cryopreservation of human embryonic stem cells by the open pulled straw
      vitrification method.
AB  - BACKGROUND: Human embryonic stem (ES) cells originate from the inner cell mass of
      the blastocyst, and retain in culture the properties of pluripotent cells of the
      early embryo. The study aim was to determine whether the open pulled straw (OPS)
      vitrification method, which is highly effective for the cryopreservation of
      embryos, might be also efficient for human ES cells. METHODS AND RESULTS: All
      human ES cell clumps that were vitrified by the OPS method could be recovered
      upon thawing, and gave rise to ES cell colonies after plating. Vitrified colonies
      were significantly smaller and showed an increased level of background
      differentiation compared with control colonies. However, these unwanted effects
      could be overcome by additional cultivation of the colonies for 1 and 2 days
      respectively. The vitrified human ES cells were cultivated for prolonged periods
      and retained the properties of pluripotent cells, including a normal karyotype,
      expression of the transcription factor Oct-4 and surface markers that are
      characteristic to human ES cells. When grafted into SCID mice, the vitrified
      cells gave rise to teratomas containing derivatives of all three embryonic germ
      layers. CONCLUSIONS: Vitrification by the OPS method is reliable and effective
      for the cryopreservation of human pluripotent embryonic stem cells.

PMID- 11574515
TI  - The accuracy of serum interleukin-6 and tumour necrosis factor as markers for
      ovarian torsion.
AB  - BACKGROUND: The aim of this study was to investigate a possible role for
      interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha) as pre-operative
      markers for the diagnosis of ovarian torsion. METHODS: Twenty consecutive
      patients admitted to the gynaecological emergency room with suspected clinical
      diagnosis of ovarian torsion were prospectively assigned to the study. Blood
      samples were drawn pre-operatively and examined for serum concentrations of IL-6
      and TNF-alpha. Surgeons were blinded to laboratory results prior to laparoscopy.
      RESULTS: The pre-operative diagnosis of ovarian torsion was confirmed during an
      urgent diagnostic laparoscopy in 8 (40%) patients. The surgical diagnosis among
      the remaining 12 patients was a large ovarian cyst not in torsion. In six out of
      eight (75.0%) patients with ovarian torsion serum IL-6 concentrations were
      elevated. None of the 12 patients without torsion had elevated serum IL-6
      concentrations. This difference was statistically significant (P < 0.001). There
      was no significant difference in the proportion of women with elevated serum TNF
      alpha concentrations, two of eight (25.0%) patients with torsion and four of 12
      (33.3%) control cases. CONCLUSIONS: Elevated serum IL-6 concentrations, but not
      serum TNF-alpha concentrations, were significantly associated with the occurrence
      of ovarian torsion. In patients with vague clinical signs of ovarian torsion,
      serum IL-6 might help to distinguish which patients should undergo diagnostic
      laparoscopy.

PMID- 11574516
TI  - Aetiology, previous menstrual function and patterns of neuro-endocrine
      disturbance as prognostic indicators in hypothalamic amenorrhoea.
AB  - BACKGROUND: Hypothalamic amenorrhoea (HA) is a syndrome associated with
      infertility and osteopenia in reproductive-age women. METHODS: To understand
      better the natural history of this disorder, 28 women participated in a
      retrospective, questionnaire-based analysis to elucidate factors associated with
      spontaneous recovery. RESULTS: 54% of subjects developed HA related to an eating
      disorder, 21% related to stress +/- weight loss, and 25% without obvious
      contributing factors (idiopathic). HA associated with a clear precipitant had a
      better prognosis than idiopathic HA (71 versus 29% recovery; P < 0.05). Reversal
      of the inciting factor appeared necessary but not sufficient for recovery (83%
      recovery if factor reversed). Normal menarche occurred in 61% of subjects,
      oligomenorrhoea in 32%, and primary amenorrhoea in 7%. Oligomenorrhoea and normal
      menarche showed a trend toward better prognosis than primary amenorrhoea (NS).
      Compared with controls, 46% of HA patients had decreased frequency of LH pulses,
      7% decreased amplitude, 18% decreases in both frequency and amplitude, 18% absent
      pulses, and 11% normal-appearing pulses. Pulse pattern at baseline did not
      predict recovery. CONCLUSIONS: The aetiology of HA at the time of presentation
      predicts subsequent recovery of menstrual function. In stress, weight loss, or
      eating disorder-related HA, rates of recovery exceeded 80% when precipitating
      factors were reversed. Idiopathic HA may represent a different disorder as
      recovery rates were <30%.

PMID- 11574517
TI  - Combined screening for Chlamydia trachomatis and squamous intra-epithelial
      lesions using a single liquid-based cervical sample.
AB  - BACKGROUND: Cervicitis is believed to alter cytological interpretation and could
      compromise a combined screening for Chlamydia trachomatis (CT) cervicitis and
      squamous intra-epithelial lesions (SIL). Liquid-based cytological methods have
      been shown to limit obscuring factors and permit the detection of infectious
      agents by DNA amplification techniques. The aim of this study was to evaluate a
      combined screening for SIL and CT cervicitis with a single liquid-based cervical
      sample. METHODS: Two cervical samples were obtained from each of 590 women
      considered at high risk for CT. The modified Ligase chain reaction (LCR)
      procedure for CT detection using specimens collected in the AutoCyte's
      preservative fluid was compared with the conventional Abbott LCx method using
      cervical swabs. We have also compared the percentage of inflammatory specimens
      and adequacy of cellular material in the populations of CT+ and CT- women.
      RESULTS: The results show total agreement for 588 of 590 cervical samples using
      the two LCR protocols (Kappa = 0.96; 95% confidence interval: 0.91-1.00). The
      quality of cervical cytology was not compromised by CT cervicitis. CONCLUSIONS:
      We demonstrated the feasibility of combined screening for CT and SIL with a
      single liquid-based cervical sample.

PMID- 11574518
TI  - Apoptosis and the expression of Bax and Bcl-2 in hyperplasia and adenocarcinoma
      of the uterine endometrium.
AB  - BACKGROUND: Apoptosis plays a crucial role in carcinogenesis in various tumours.
      This study was designed to investigate the occurrence of apoptosis and the
      expression of Bcl-2 and Bax proteins in endometrial tumours of corpus uteri.
      METHODS: Endometrial tissues were obtained from 20 patients with endometrioid
      adenocarcinoma, 16 patients with endometrial hyperplasia, and 4 patients with
      myoma uteri (which were used as controls). The occurrence of apoptosis was
      examined by using molecular biochemical techniques. The expression of Bcl-2 and
      Bax proteins was also investigated using immunohistochemical staining with
      appropriate antibodies. RESULTS: The labelling of DNA in situ indicated that
      apoptotic cells were sporadically seen in postmenopausal endometrium (5.2 +/-
      2.1, n = 4) and endometrial hyperplasia without atypia (2.6 +/- 0.5, n = 9). In
      contrast, labelled cells were detected in atypical endometrial hyperplasia (15.9
      +/- 2.2, n = 7), and their numbers increased intensely in adenocarcinoma (29.3 +/
      3.7, n = 20). Autoradiographic analysis revealed DNA laddering in many cases of
      carcinoma. Bcl-2 was highly immunopositive in hyperplasia without atypia (36.2 +/
      6.5%, n = 9), but was decreased in the atypical endometrial hyperplasia (16.3 +/
      4.8%, n = 7). Large fractions of the carcinoma (6.3 +/- 1.8%, n = 20) and normal
      endometrium (2.8 +/- 1.4%, n = 4) were immunonegative or slightly immunopositive
      to Bcl-2. In contrast, Bax immunoreactivity was more frequent and stronger in
      adenocarcinoma (43.6 +/- 4.1%, n = 20) than that in normal endometrium (17.6 +/-
      6.7%, n = 4) and hyperplasia (7.2 +/- 2.2%, n = 16). CONCLUSIONS: These results
      suggest that cells in hyperplasia expressing Bcl-2 might have prolonged survival
      ability. Neoplastic cells in adenocarcinoma might show apoptosis in association
      with a decreased expression of Bcl-2 and an increased expression of Bax.
      Therefore, the frequency of apoptosis and the expression of Bcl-2 and Bax might
      be correlated with carcinogenesis in the uterine endometrium of humans.

PMID- 11574519
TI  - Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and
      with subsequent abortions.
AB  - BACKGROUND: This study compared Th1-Th2 cytokine profiles in a subgroup of
      recurrent aborters who had an abortion with those in a subgroup of recurrent
      aborters who had a successful pregnancy. METHODS: Fifty-four women with a history
      of at least three normal pregnancies, 24 women with a history of recurrent
      spontaneous abortion (RSA) followed by abortion (RSA-->A) and 39 women with a
      history of RSA followed by normal pregnancy (RSA-->N) were studied. Blood samples
      and placentas were obtained at the time of delivery or abortion; peripheral blood
      mononuclear cells were stimulated separately with phytohaemagglutinin and with
      autologous placental cells, and the secreted cytokines estimated. RESULTS:
      Peripheral blood mononuclear cells from the RSA-->N subgroup secreted higher
      concentrations of Th1-type cytokines as compared with normal pregnant women,
      indicating a higher Th1 bias in these women. However, women in the RSA-->N
      subgroup had significantly higher concentrations of Th2 cytokines as compared
      with women in the RSA-->A subgroup. A comparison of Th1:Th2 cytokine ratios
      indicated a higher Th2 bias in RSA-->N women as compared with RSA-->A women.
      CONCLUSIONS: We conclude that abortion-prone women who proceed to have successful
      pregnancy are more Th2-biased than abortion-prone women who abort, and that
      recurrent aborters who undergo spontaneous abortion have a stronger Th1 bias than
      aborters who have normal pregnancy.

PMID- 11574520
TI  - Rare association of ovarian implantation site for patients with heterotopic and
      with primary ectopic pregnancies after ICSI and blastocyst transfer.
AB  - Two cases of patients with ruptured ovarian pregnancies (P1 = ovarian heterotopic
      and P2 = primary ovarian ectopic) after intracytoplasmic sperm injection and
      blastocyst transfer are presented. Laparoscopy was performed on day 40 and day 27
      after transfer in cases P1 and P2 respectively. In both cases the ectopic
      pregnancies were located on the left ovary and were successfully removed by
      laparoscopy preserving the ovaries. In case P1 the intrauterine pregnancy was not
      affected. A healthy boy was born after 37 weeks of pregnancy. In this way,
      potential fertility of the patients and the intrauterine pregnancy were
      maintained. These cases occurred during a series of blastocyst transfers in which
      129 pregnancies were obtained. There were no cases of ovarian ectopic/heterotopic
      pregnancies from January 1996 to September 1999 in 814 pregnancies obtained from
      day 2 or day 3 embryo transfers. Because the ovarian ectopic pregnancies occurred
      in patients with day 5 embryo transfer who otherwise did not have any
      predisposing factors for ectopic pregnancy, it is advisable to conduct a large
      scale analysis of future data about the possible association between blastocyst
      stage embryo transfer and the somewhat higher risk of unexpected complications of
      clinical outcome.

PMID- 11574521
TI  - Declining incidence of ectopic pregnancy in a UK city health district between
      1990 and 1999.
AB  - BACKGROUND: On the basis of clinical impression that the number of cases of
      ectopic pregnancy seen in the City and Hackney Health District, London, was
      changing, a retrospective study of the years between 1990 and 1999 was carried
      out. METHODS: From the histopathology databases, cases of ectopic pregnancy and
      early pregnancy failure were identified. The number of deliveries at The Homerton
      Hospital was obtained from the Labour Ward register; the number of terminations
      of pregnancy and the number of fertile women was obtained from the Office for
      National Statistics, UK. RESULTS: There were 73 cases of ectopic pregnancy in
      1990 rising to 96 in 1991 and then a fall to 52 cases in 1999. In terms of
      ectopic pregnancy per 100 deliveries, per all known pregnancies and per 1000
      fertile women per year, there was a peak in 1991 and a fall to 1999. With regard
      to relative incidence per deliveries and per all known pregnancies, these falls
      were significant (P < 0.05). In 1991, there were 2.4 ectopic pregnancies per 100
      deliveries, falling to 1.6 in 1999, a 33% fall. The reasons for this large
      decline are uncertain. CONCLUSIONS: There has been no change in patient
      population, diagnostic aids used or management protocols for patients with
      ectopic pregnancies.

PMID- 11574522
TI  - Screening for human papillomavirus infection in asymptomatic women in Hungary.
AB  - BACKGROUND: A multicentre epidemiological survey was carried out in order to
      determine the prevalence of, and risk factors for, persistent cervical human
      papillomavirus (HPV) infection in women in Hungary. METHODS AND RESULTS: A total
      of 728 women were examined for the prevalence of HPV. The estimated overall rate
      of HPV infection was 17%. In univariate analysis the strongest predictors were
      young age (< or =24 years), unmarried family status, smoking, a pathological
      Papanicolaou (Pap) smear, having a condyloma and previous gynaecological cancer
      in the family (age and marital status being the most important predictors). In
      multiple regression analysis, young age (< or =24 years)(odds ratio = 1.86, 95%
      confidence interval = 1.19-2.90, P < 0.01), smoking (1.78, 1.17-2.71, P < 0.05),
      an abnormal Pap smear (6.92, 2.68-17.84, P < 0.001), having a condyloma (4.22,
      1.42-12.58, P < 0.01) and living in a region where the unemployment rate is
      relatively high (1.56, 1.24-2.82, P < 0.01) were associated risk factors for HPV
      infection. CONCLUSIONS: The prevalence of HPV infection in young women in Hungary
      is high. Screening for HPV is suggested only in women with an unfavourable
      gynaecological history who are < or =24 years old.

PMID- 11574523
TI  - Fetal antecedents of male factor sub-fertility: how important is birthweight?
AB  - BACKGROUND: Severely reduced fetal growth has been linked to gonadal dysfunction.
      The aim of this study was to explore the link between birthweight and subsequent
      male infertility using the Aberdeen Maternity and Neonatal Databank (AMND).
      METHODS AND RESULTS: Assuming 80% power at the 5% significance level, a minimum
      of 126 men (63 in each group) was required to show a mean difference of 0.5 (SD =
      1) in the standardized birthweight scores between cases and controls. Men born
      locally with unexplained male factor infertility (n = 79) were identified from
      the infertility clinic database. Men with normal semen parameters, born in
      Aberdeen and attending the infertility clinic with their partners (n = 104),
      served as controls. The pregnancy records of these men's mothers were obtained
      from the AMND and a standard case-control analysis performed. In addition to
      standardized birthweight scores, the following variables were studied: crude
      birthweight, social class, maternal age, parity, obstetric history, antepartum
      and peripartum events. CONCLUSIONS: No differences were found between the two
      groups, suggesting that low birthweight is unlikely to affect male fertility in
      later life.

PMID- 11574524
TI  - Mifepristone (RU486) and voluntary termination of pregnancy: enigmatic variations
      or anecdotal religion-based attitudes?

PMID- 11574525
TI  - Secrecy and openness in donor offspring.

PMID- 11574526
TI  - Parental ages and the secondary sex ratio.

PMID- 11574527
TI  - Secrecy and openness in donor offspring.

PMID- 11574528
TI  - Variation in the human sex ratio at birth with maternal age, parity and placental
      pathology.

PMID- 11574529
TI  - Historical comment on the debate: embryo implantation is the rubicon for the GnRH
      antagonist, and answer.

PMID- 11574530
TI  - Pharmacological knock-down of the presenilin 1 heterodimer by a novel gamma 
      secretase inhibitor: implications for presenilin biology.
AB  - Intramembranous cleavage of the beta-amyloid precursor protein by gamma-secretase
      is the final processing event generating amyloid-beta peptides, which are thought
      to be causative agents for Alzheimer's disease. Missense mutations in the
      presenilin genes co-segregate with early-onset Alzheimer's disease, and,
      recently, a close biochemical linkage between presenilins and the identity of
      gamma-secretase has been established. Here we describe for the first time that
      certain potent gamma-secretase inhibitors are able to interfere with the
      endoproteolytic processing of presenilin 1 (PS1). In addition, we identified a
      novel gamma-secretase inhibitor, [1S-benzyl-4R-[1-(5-cyclohexyl-2-oxo-2,3-dihydro
      1H-benzo[e][1,4]diazepin-3(R,S)-ylcarbamoyl)-S-ethylcarbamoyl]-2R-hydroxy-5
      phenyl-pentyl]-carbamic acid tert-butyl ester (CBAP), which not only physically
      interacts with PS1, but upon chronic treatment produces a "pharmacological knock
      down" of PS1 fragments. This indicates that the observed accumulation of full
      length PS1 is caused by a direct inhibition of its endoproteolysis. The
      subsequent use of CBAP as a biological tool to increase full-length PS1 levels in
      the absence of exogenous PS1 expression has provided evidence that wild-type PS1
      endoproteolysis is not required either for PS1/gamma-secretase complex assembly
      or trafficking. Furthermore, in cell-based systems CBAP does not completely
      recapitulate PS1 loss-of-function phenotypes. Even though the beta-amyloid
      precursor protein cleavage and the S3 cleavage of the Notch receptor are
      inhibited by CBAP, an impairment of Trk receptor maturation was not observed.

PMID- 11574531
TI  - Ribosomal protein S6 phosphorylation and function during late gestation liver
      development in the rat.
AB  - The phosphorylation of ribosomal protein S6 is thought to be required for
      biosynthesis of the cell's translational apparatus, a critical component of cell
      growth and proliferation. We have studied the signal transduction pathways
      involved in hepatic S6 phosphorylation during late gestation in the rat. This is
      a period during which hepatocytes show a high rate of proliferation that is, at
      least in part, independent of mitogenic signaling pathways that are operative in
      mature hepatocytes. Our initial studies demonstrated that there was low basal
      activity of two S6 kinases in liver, S6K1 and S6K2, on embryonic day 19 (2 days
      preterm). In addition, insulin- and growth factor-mediated S6K1 and S6K2
      activation was markedly attenuated compared with that in adult liver.
      Nonetheless, two-dimensional gel electrophoresis demonstrated that fetal liver S6
      itself was highly phosphorylated. To characterize the fetal hepatocyte pathway
      for S6 phosphorylation, we went on to study the sensitivity of hepatocyte
      proliferation to the S6 kinase inhibitor rapamycin. Unexpectedly, administration
      of rapamycin to embryonic day 19 fetuses in situ did not affect hepatocyte DNA
      synthesis. This resistance to the growth inhibitory effect of rapamycin occurred
      even though S6K1 and S6K2 were inhibited. Furthermore, fetal hepatocyte
      proliferation was sustained even though rapamycin administration resulted in the
      dephosphorylation of ribosomal protein S6. In contrast, rapamycin blocked hepatic
      DNA synthesis in adult rats following partial hepatectomy coincident with S6
      dephosphorylation. We conclude that hepatocyte proliferation in the late
      gestation fetus is supported by a rapamycin-resistant mechanism that can function
      independently of ribosomal protein S6 phosphorylation.

PMID- 11574532
TI  - Complementing yeast rho1 mutation groups with distinct functional defects.
AB  - Saccharomyces cerevisiae is a multifunctional molecular switch involved in
      establishment of cell morphogenesis. We systematically characterized isolated
      temperature-sensitive mutations in the RHO1 gene and identified two groups of
      rho1 mutations (rho1A and rho1B) possessing distinct functional defects.
      Biochemical and cytological analyses demonstrated that mutant cells of the rho1A
      and rho1B groups have defects in activation of the Rho1p effectors Pkc1p kinase
      and 1,3-beta-glucan synthase, respectively. Heteroallelic diploid strains with
      rho1A and rho1B mutations were able to grow even at the restrictive temperature
      of the corresponding homoallelic diploid strains, showing intragenic
      complementation. The ability to activate both of the essential Rho1p effector
      proteins was restored in the heteroallelic diploid. Thus, each of the
      complementing rho1 mutation groups abolishes a distinct function of Rho1p,
      activation of Pkc1p kinase or 1,3-beta-glucan synthase activity.

PMID- 11574533
TI  - Reactivation of peroxisome proliferator-activated receptor alpha is associated
      with contractile dysfunction in hypertrophied rat heart.
AB  - In pressure overload-induced hypertrophy, the heart increases its reliance on
      glucose as a fuel while decreasing fatty acid oxidation. A key regulator of this
      substrate switching in the hypertrophied heart is peroxisome proliferator
      activated receptor alpha (PPARalpha). We tested the hypothesis that down
      regulation of PPARalpha is an essential component of cardiac hypertrophy at the
      levels of increased mass, gene expression, and metabolism by pharmacologically
      reactivating PPARalpha. Pressure overload (induced by constriction of the
      ascending aorta for 7 days in rats) resulted in cardiac hypertrophy, increased
      expression of fetal genes (atrial natriuretic factor and skeletal alpha-actin),
      decreased expression of PPARalpha and PPARalpha-regulated genes (medium chain
      acyl-CoA dehydrogenase and pyruvate dehydrogenase kinase 4), and caused substrate
      switching (measured ex vivo in the isolated working heart preparation). Treatment
      of rats with the specific PPARalpha agonist WY-14,643 (8 days) did not affect the
      trophic response or atrial natriuretic factor induction to pressure overload.
      However, PPARalpha activation blocked skeletal alpha-actin induction, reversed
      the down-regulation of measured PPARalpha-regulated genes in the hypertrophied
      heart, and prevented substrate switching. This PPARalpha reactivation
      concomitantly resulted in severe depression of cardiac power and efficiency in
      the hypertrophied heart (measured ex vivo). Thus, PPARalpha down-regulation is
      essential for the maintenance of contractile function of the hypertrophied heart.

PMID- 11574535
TI  - An isoform of branched-chain aminotransferase is a novel co-repressor for thyroid
      hormone nuclear receptors.
AB  - The functions of thyroid hormone receptors (TRs) are regulated by a host of co
      regulatory proteins. Tissue-specific expression of these co-regulators leads to
      distinct expression patterns and regulation of thyroid hormone (T3) target genes
      in tissues. Previously we have found that human colon carcinoma RKO cells exhibit
      strong T3-independent transcriptional activity. We therefore searched for co
      regulatory proteins in RKO cells using a yeast two-hybrid system with the intact
      TRbeta1 as bait. One of the three positive clones, designated as P3, was
      identified to be an isoform of human mitochondria branched-chain aminotransferase
      (BCATm). P3 was a spliced variant of BCATm with an internal 12-amino acid
      deletion near the carboxyl-terminal region and was abundantly expressed in RKO
      cells. The expressed protein localized both to the mitochondria and the nucleus
      of transfected CV1 cells. P3 physically interacted with TRbeta1 in a T3
      independent manner that led to the inhibition in binding of TRbeta1 to thyroid
      hormone-responsive element. P3 not only enhanced the repressor activity of the
      unliganded TR but also repressed the ligand-dependent activation of TR. This
      repression was reversed by treatment of cells with trichostatin A, suggesting
      that in addition to the inhibition of DNA binding, the repression activity of P3
      on TR may also be mediated by histone deacetylase activity. Thus, unlike the
      currently known co-repressors, P3 is a novel ligand-independent co-repressor for
      TR.

PMID- 11574536
TI  - Geldanamycin restores a defective heat shock response in vivo.
AB  - Induced expression of heat shock proteins (Hsps) plays a central role in
      promoting cellular survival after environmental and physiological stress. We have
      previously shown that scrapie-infected mouse neuroblastoma (ScN2a) cells fail to
      induce the expression of Hsp72 and Hsp28 after various stress conditions. Here we
      present evidence that this impaired stress response is due to an altered
      regulation of HSF1 activity. Upon stress in ScN2a cells, HSF1 was converted into
      hyperphosphorylated trimers but failed to acquire transactivation competence. A
      kinetic analysis of HSF1 activation revealed that in ScN2a cells trimer formation
      after stress was efficient, but disassembly of trimers proceeded much faster than
      in the uninfected cell line. Geldanamycin, a Hsp90-binding drug, significantly
      delayed disassembly of HSF1 trimers after a heat shock and restored stress
      induced expression of Hsp72 in ScN2a cells. Heat-induced Hsp72 expression
      required geldanamycin to be present; following removal of the drug ScN2a cells
      again lost their ability to mount a stress response. Thus, our studies show that
      a defective stress response can be pharmacologically restored and suggest that
      the HSF1 deactivation pathway may play an important role in the regulation of Hsp
      expression.

PMID- 11574534
TI  - Endoplasmic reticulum stress-induced cysteine protease activation in cortical
      neurons: effect of an Alzheimer's disease-linked presenilin-1 knock-in mutation.
AB  - Endoplasmic reticulum (ER) stress elicits protective responses of chaperone
      induction and translational suppression and, when unimpeded, leads to caspase
      mediated apoptosis. Alzheimer's disease-linked mutations in presenilin-1 (PS-1)
      reportedly impair ER stress-mediated protective responses and enhance
      vulnerability to degeneration. We used cleavage site-specific antibodies to
      characterize the cysteine protease activation responses of primary mouse cortical
      neurons to ER stress and evaluate the influence of a PS-1 knock-in mutation on
      these and other stress responses. Two different ER stressors lead to processing
      of the ER-resident protease procaspase-12, activation of calpain, caspase-3, and
      caspase-6, and degradation of ER and non-ER protein substrates.
      Immunocytochemical localization of activated caspase-3 and a cleaved substrate of
      caspase-6 confirms that caspase activation extends into the cytosol and nucleus.
      ER stress-induced proteolysis is unchanged in cortical neurons derived from the
      PS-1 P264L knock-in mouse. Furthermore, the PS-1 genotype does not influence
      stress-induced increases in chaperones Grp78/BiP and Grp94 or apoptotic
      neurodegeneration. A similar lack of effect of the PS-1 P264L mutation on the
      activation of caspases and induction of chaperones is observed in fibroblasts.
      Finally, the PS-1 knock-in mutation does not alter activation of the protein
      kinase PKR-like ER kinase (PERK), a trigger for stress-induced translational
      suppression. These data demonstrate that ER stress in cortical neurons leads to
      activation of several cysteine proteases within diverse neuronal compartments and
      indicate that Alzheimer's disease-linked PS-1 mutations do not invariably alter
      the proteolytic, chaperone induction, translational suppression, and apoptotic
      responses to ER stress.

PMID- 11574538
TI  - The UV-inducible RNA-binding protein A18 (A18 hnRNP) plays a protective role in
      the genotoxic stress response.
AB  - We have previously shown that specific RNA-binding proteins (RBP) are activated
      by genotoxic stress. The role and function of these stress-activated RBP are,
      however, poorly understood. The data presented here indicate that the RBP A18
      heterogeneous ribonucleoprotein (hnRNP) is induced and translocated from the
      nuclei to the cytoplasm after exposure to UV radiation. Using a new in vitro
      system we identified potential cellular targets for A18 hnRNP. Forty-six mRNA
      transcripts were identified, most of which are stress- or UV-responsive genes.
      Two important stress-responsive transcripts, the replication protein A (RPA2) and
      thioredoxin, were studied in more detail. Northwestern analyses indicate that A18
      hnRNP binds specifically to the 3'-untranslated region of RPA2 transcript
      independently of its poly(A) tail, whereas the poly(A) tail of thioredoxin mRNA
      reinforces binding. Overexpression of A18 hnRNP increases the mRNAs stability and
      consequently enhances translation in a dose-dependent manner. Moreover, cell
      lines expressing reduced levels of A18 hnRNP are more sensitive to UV radiation.
      These data suggest that A18 hnRNP plays a protective role against genotoxic
      stresses by translocating to the cytosol and stabilizing specific transcripts
      involved in cell survival.

PMID- 11574537
TI  - Signal transduction pathways mediating neurotensin-stimulated interleukin-8
      expression in human colonocytes.
AB  - Neurotensin (NT), a neuropeptide released in the gastrointestinal tract in
      response to several stimuli, is involved in the pathophysiology of colonic
      inflammation. However, the molecular mechanism(s) mediating this proinflammatory
      response remains unclear. We found that NCM460, non-transformed human
      colonocytes, express a functional high affinity NT receptor that mediates NT
      induced Erk activation. By using NCM460 cells stably transfected with NTR1, we
      show that NTR1 activation leads to interleukin (IL)-8 secretion that is mediated
      via both NF-kappaB- and Erk-dependent pathways. In addition, NT-stimulated NF
      kappaB activation is dependent on intracellular calcium release. NT-stimulated
      Erk activity requires Ras activation because overexpression of the dominant
      negative Ras mutant Ras-17N almost completely inhibits the Erk activation.
      Furthermore, NT directly stimulates Ras-GTP formation as shown by a Ras-GTP pull
      down assay. By using reporter gene constructs containing targeted substitutions
      in the IL-8 promoter, we show that the NF-kappaB, AP-1, and to a lesser degree
      the C/EBP sites in the IL-8 promoter region are required for IL-8 gene expression
      induced by NT. In summary, our results demonstrate that NT stimulates calcium
      dependent NF-kappaB and Ras-dependent Erk pathways that mediate the release of IL
      8 from non-transformed human colonocytes. We speculate that these NT-related
      proinflammatory pathways are important in the pathophysiology of colonic
      inflammation.

PMID- 11574539
TI  - Roles of phytanoyl-CoA alpha-hydroxylase in mediating the expression of human
      coagulation factor VIII.
AB  - The coagulation factor VIII (FVIII) is the coagulation factor deficient in the X
      chromosome-linked bleeding disorder hemophilia A. Previous transfection studies
      demonstrated that factor VIII was 10-100-fold less efficiently expressed than the
      homologous coagulation factor, factor V. To investigate the regulatory mechanisms
      of FVIII synthesis and secretion, we used the yeast two-hybrid system as an
      approach to search for proteins that associated with FVIII. The A2 domain (337
      740 amino acids) of factor VIII (FVIII-A2) was used as a bait and phytanoyl-CoA
      alpha-hydroxylase (PAHX) was identified as a binding protein of FVIII-A2. PAHX
      had potential to interact with the residues 373-508 within the A2 domain, but not
      with A1 and A3 (the homologous domains of A2). The interaction between the A2
      domain and PAHX was independent of the type 2 peroxisomal targeting signal (PTS2)
      of PAHX. Overexpression of PAHX in FVIII-produced cells decreased the expression
      of FVIII by about 70%. The elevated expression of von Willebrand factor had no
      effect on the suppression of FVIII secretion by PAHX. Expression of the green
      fluorescent PAHX fusion protein in SMMC-7721 cells affected the intracellular
      trafficking of FVIII-A2. These results suggested that the interaction between
      PAHX and FVIII-A2 was in part responsible for the low-level expression of factor
      VIII.

PMID- 11574540
TI  - Multiple forms of mouse vascular endothelial growth factor-D are generated by RNA
      splicing and proteolysis.
AB  - The secreted glycoprotein vascular endothelial growth factor-D (VEGF-D) is
      angiogenic, lymphangiogenic, and promotes metastatic spread of tumor cells via
      lymphatic vessels. VEGF-D consists of a receptor-binding domain (VEGF homology
      domain) and N- and C-terminal propeptides. Proteolytic processing produces
      numerous forms of human VEGF-D, including fully processed derivatives (containing
      only the VEGF homology domain), partially processed, and unprocessed derivatives.
      Proteolysis is essential to generate human VEGF-D that binds the angiogenic
      receptor VEGF receptor-2 (VEGFR-2) and the lymphangiogenic receptor VEGFR-3 with
      high affinity. Here, we report that alternative use of an RNA splice donor site
      in exon 6 of the mouse VEGF-D gene produces two different protein isoforms, VEGF
      D(358) and VEGF-D(326), with distinct C termini. The two isoforms were both
      expressed in all adult mouse tissues and embryonic stages of development
      analyzed. Both isoforms are proteolytically processed in a similar fashion to
      human VEGF-D to generate a range of secreted derivatives and bind and cross-link
      VEGFR-3 with similar potency. The isoforms are differently glycosylated when
      expressed in vitro. This study demonstrates that RNA splicing, protein
      glycosylation, and proteolysis are mechanisms for generating structural diversity
      of mouse VEGF-D.

PMID- 11574541
TI  - Estrogen response elements alter coactivator recruitment through allosteric
      modulation of estrogen receptor beta conformation.
AB  - Estrogen receptor beta (ERbeta) activates transcription by binding to estrogen
      response elements (EREs) and coactivator proteins that act as bridging proteins
      between the receptor and the basal transcription machinery. Although the
      imperfect vitellogenin B1, pS2, and oxytocin (OT) EREs each differ from the
      consensus vitellogenin A2 ERE sequence by a single base pair, ERbeta activates
      transcription of reporter plasmids containing A2, pS2, B1, and OT EREs to
      different extents. To explain how these differences in transactivation might
      occur, we have examined the interaction of ERbeta with these EREs and monitored
      recruitment of the coactivators amplified in breast cancer (AIB1) and
      transcription intermediary factor 2 (TIF2). Protease sensitivity, antibody
      interaction, and DNA pull-down assays demonstrated that ERbeta undergoes ERE
      dependent changes in conformation resulting in differential recruitment of AIB1
      and TIF2 to the DNA-bound receptor. Overexpression of TIF2 or AIB1 in transient
      transfection assays differentially enhanced ERbeta-mediated transcription of
      reporter plasmids containing the A2, pS2, B1, and OT EREs. Our studies
      demonstrate that individual ERE sequences induce changes in conformation of the
      DNA-bound receptor and influence coactivator recruitment. DNA-induced modulation
      of receptor conformation may contribute to the ability of ERbeta to
      differentially activate transcription of genes containing divergent ERE
      sequences.

PMID- 11574542
TI  - A novel carbamoyl-phosphate synthetase from Aquifex aeolicus.
AB  - Aquifex aeolicus, an extreme hyperthermophile, has neither a full-length
      carbamoyl-phosphate synthetase (CPSase) resembling the enzyme found in all
      mesophilic organisms nor a carbamate kinase-like CPSase such as those present in
      several hyperthermophilic archaea. However, the genome has open reading frames
      encoding putative proteins that are homologous to the major CPSase domains. The
      glutaminase, CPS.A, and CPS.B homologs from A. aeolicus were cloned,
      overexpressed in Escherichia coli, and purified to homogeneity. The isolated
      proteins could catalyze several partial reactions but not the overall synthesis
      of carbamoyl phosphate. However, a stable 124-kDa complex could be reconstituted
      from stoichiometric amounts of CPS.A and CPS.B proteins that synthesized
      carbamoyl phosphate from ATP, bicarbonate, and ammonia. The inclusion of the
      glutaminase subunit resulted in the formation of a 171-kDa complex that could
      utilize glutamine as the nitrogen-donating substrate, although the catalytic
      efficiency was significantly compromised. Molecular modeling, using E. coli
      CPSase as a template, showed that the enzyme has a similar structural
      organization and interdomain interfaces and that all of the residues known to be
      essential for function are conserved and properly positioned. A steady state
      kinetic study at 78 degrees C indicated that although the substrate affinity was
      similar for bicarbonate, ammonia, and glutamine, the K(m) for ATP was appreciably
      higher than that of any known CPSase. The A. aeolicus complex, with a split gene
      encoding the major synthetase domains and relatively inefficient coupling of
      amidotransferase and synthetase functions, may be more closely related to the
      ancestral precursor of contemporary mesophilic CPSases.

PMID- 11574543
TI  - The G2/M regulator 14-3-3sigma prevents apoptosis through sequestration of Bax.
AB  - In response to DNA damage and genotoxic stress, the p53 tumor suppressor triggers
      either cell cycle arrest or apoptosis. The G(2) arrest after damage is, in part,
      mediated by the p53 target, 14-3-3final sigma (final sigma). Colorectal tumor
      cells lacking final sigma are exquisitely sensitive to DNA damage. Here we
      analyzed the mechanism of this sensitivity in final sigma(-/-) as compared with
      final sigma(+/+) human colorectal tumor cells. Exposure to adriamycin resulted in
      rapid apoptosis only in final sigma(-/-) cells. This was further characterized by
      caspase-3 activation, p21(CIP1) cleavage, and CDK2 activation. Moreover, Bax was
      rapidly translocated out of the cytoplasm, and cytochrome c was released in final
      sigma(-/-) cells. Transient adenovirus-mediated reconstitution of final sigma in
      the final sigma(-/-) cells led to effective rescue of this phenotype and
      protected cells against apoptosis. The association of final sigma, Bax, and CDK1
      in protein complexes may be the basis for this antiapoptotic mechanism. In
      conclusion, final sigma not only enforces the p53-dependent G(2) arrest but also
      delays the apoptotic signal transduction.

PMID- 11574544
TI  - Heme A is not essential for assembly of the subunits of cytochrome c oxidase of
      Rhodobacter sphaeroides.
AB  - The aa(3)-type cytochrome c oxidase of Rhodobacter sphaeroides, a proteobacterium
      of the alpha subgroup, is structurally similar to the core subunits of the
      terminal oxidase in the mitochondrial electron transport chain. Subunit I, the
      product of the coxI gene, normally binds two heme A molecules. A deletion of
      cox10, the gene for the farnesyltransferase required for heme A synthesis, did
      not prevent high level accumulation of subunit I in the cytoplasmic membrane.
      Thus, subunit I can be expressed and stably inserted into the cytoplasmic
      membrane in the absence of heme A. Aposubunit I was purified via affinity
      chromatography to a polyhistidine tag. Copurification of subunits II and III with
      aposubunit I indicated that assembly of the core oxidase complex occurred without
      the binding of heme A. In addition to formation of the apooxidase containing all
      three large structural proteins, CoxI-II and CoxI-III heterodimers were isolated
      from cox10 deletion strains harboring expression plasmids with coxI and coxII or
      with coxI and coxIII, respectively. This demonstrated that subunit assembly of
      the apoenzyme was not an inherently ordered or sequential process. Thus, multiple
      paths must be considered for understanding the assembly of this integral membrane
      metalloprotein complex.

PMID- 11574545
TI  - Regulation of apoptosis during neuronal differentiation by ceramide and b-series
      complex gangliosides.
AB  - Lipid analysis of gestational day E14.5 mouse brain revealed elevation of
      ceramide to a tissue concentration that induced apoptosis when added to the
      medium of neuroprogenitor cells grown in cell culture. Elevation of ceramide was
      coincident with the first appearance of b-series complex gangliosides (BCGs).
      Expression of BCGs by stable transfection of murine neuroblastoma (F-11) cells
      with sialyltransferase-II (ST2) resulted in a 70% reduction of ceramide-induced
      apoptosis. This was most likely due to an 80% reduced expression of prostate
      apoptosis response-4 (PAR-4). PAR-4 expression and apoptosis were restored by
      preincubation of ST2-transfected cells with N-butyl deoxinojirimycin (NB-DNJ) or
      PD98059, two inhibitors of ganglioside biosynthesis or p42/44 mitogen-activated
      protein (MAPK) kinase, respectively. In sections of day E14.5 mouse brain, the
      intermediate zone showed intensive staining for complex gangliosides, but only
      low staining for apoptosis (TUNEL) and PAR-4. Apoptosis and PAR-4 expression,
      however, were elevated in the ventricular zone which only weakly stained for
      complex gangliosides. Whole cell patch clamping revealed a 2-fold increased
      calcium influx in ST2-transfected cells, the blocking of which with nifedipine
      restored apoptosis to the level of untransfected cells. In serum-free culture,
      supplementation of the medium with IGF-1 was required to maintain MAPK
      phosphorylation and the anti-apoptotic effect of BCG expression. BCG-enhanced
      calcium influx and the presence of insulin-like growth factor-1 may thus activate
      a cell survival mechanism that selectively protects developing neurons against
      ceramide-induced apoptosis by up-regulation of MAPK and reduction of PAR-4
      expression.

PMID- 11574546
TI  - The von Hippel-Lindau tumor suppressor protein mediates ubiquitination of
      activated atypical protein kinase C.
AB  - The von Hippel-Lindau tumor-suppressor protein (pVHL) forms a protein complex
      (VCB-Cul2) with elongin C, elongin B, Cul-2, and Rbx1, which functions as a
      ubiquitin-protein ligase (E3). The alpha-subunits of the hypoxia-inducible
      factors have been identified as targets for the VCB-Cul2 ubiquitin ligase.
      However, a variety of cellular defects caused by the depletion of pVHL cannot be
      explained solely by the ubiquitin-mediated degradation of hypoxia-inducible
      factor-alpha. We show here that a member of the atypical protein kinase C (PKC)
      group, PKClambda, is ubiquitinated by the pVHL-containing E3 enzyme. An active
      PKClambda mutant is ubiquitinated more extensively than wild-type PKClambda in
      HEK293 cells, and the ubiquitination is further enhanced by the overexpression of
      pVHL. The activation of wild-type PKClambda by serum stimulation of cells
      enhances the ubiquitination of the protein, supporting the notion that active
      PKClambda is preferentially ubiquitinated by VCB-Cul2 ubiquitin ligase.
      Furthermore, we show that PKClambda can be ubiquitinated in vitro in a cell-free
      ubiquitination assay using purified recombinant components including VCB-Cul2.
      Given the known function of aPKC in the regulation of cell polarity and cell
      growth, PKClambda may be a target of pVHL in its function as a tumor suppressor.

PMID- 11574547
TI  - Transcriptional activation by STAT6 requires the direct interaction with NCoA-1.
AB  - Signal transducer and activator of transcription 6 (STAT6) is a transcription
      factor that is activated by interleukin-4 (IL-4)-induced tyrosine phosphorylation
      and mediates most of the IL-4-induced gene expression. Transcriptional activation
      by STAT6 requires the interaction with coactivators like p300 and the CREB
      binding protein (CBP). In this study we have investigated the function of the CBP
      associated members of the p160/steroid receptor coactivator family in the
      transcriptional activation by STAT6. We found that only one of them, NCoA-1, acts
      as a coactivator for STAT6 and interacts directly with the transactivation domain
      of STAT6. The N-terminal part of NCoA-1 interacts with the far C-terminal part of
      the STAT6 transactivation domain but does not interact with the other members of
      the STAT family. This domain of NCoA-1 has a strong inhibitory effect on STAT6
      mediated transactivation when overexpressed in cells, illustrating the importance
      of NCoA-1 for STAT6-mediated transactivation. In addition, we showed that both
      coactivators CBP and NCoA-1 bind independently to specific regions within the
      STAT6 transactivation domain. Our results suggest that multiple contacts between
      NCoA-1, CBP, and STAT6 are required for transcriptional activation. These
      findings provide new mechanistic insights into how STAT6 can recruit coactivators
      required for IL-4-dependent transactivation.

PMID- 11574548
TI  - Functional analysis of novel multidrug transporters from human pathogens.
AB  - Proteins of the Smr family are the smallest multidrug transporters, about 110
      amino acids long, that extrude various drugs in exchange with protons, thereby
      rendering bacteria resistant to these compounds. One of these proteins, EmrE, is
      an Escherichia coli protein, which has been cloned based on its ability to confer
      resistance to ethidium and methyl viologen and which has been extensively
      characterized. More than 60 genes coding for Smr proteins have been identified in
      several bacteria based on amino acid sequence similarity to the emrE gene. In
      this work we have analyzed the sequence similarity among these homologues and
      identified some distinct signature sequence elements and several fully conserved
      residues. Five of these homologues, from human pathogens Mycobacterium
      tuberculosis, Bordetella pertussis, and Pseudomonas aeruginosa and from
      Escherichia coli, were cloned into an E. coli expression system. The proteins
      were further characterized and show varying degrees of methyl viologen uptake
      into proteoliposomes and [(3)H]TPP binding in solubilized membranes. The
      homologues can also form mixed oligomers with EmrE that exhibit intermediate
      binding characteristics. A comparative study of various homologous proteins
      provides a tool for deciphering structure-function relationship and monomer
      monomer interaction in multidrug transporters and in membrane proteins in
      general.

PMID- 11574549
TI  - Inhibition of axotomy-induced neuronal apoptosis by extracellular delivery of a
      Bcl-XL fusion protein.
AB  - Bcl-2 and Bcl-XL prevent neuronal apoptosis during development, neurodegenerative
      disease, and trauma. To test a new anti-apoptosis strategy for neuroprotection,
      we engineered nontoxic components of anthrax toxin into a Bcl-XL delivery system.
      Delivery of Bcl-XL by this system prevented apoptosis of cultured rat cerebellar
      granule cells and macrophages, and the prevention depended on both the Bcl-XL and
      the anthrax toxin receptor binding/translocation moieties. Furthermore, neuronal
      death in vivo in a retinal ganglion cell model of axotomy-induced apoptosis was
      inhibited by administration of this fusion protein. Thus, Bcl-XL protein can be
      delivered into cells from the medium or interstitial space, offering a new way to
      block apoptosis upstream of many caspases and the mitochondria dysfunction phase
      of apoptosis.

PMID- 11574550
TI  - RecA protein filaments disassemble in the 5' to 3' direction on single-stranded
      DNA.
AB  - RecA protein forms filaments on both single- and double-stranded DNA. Several
      studies confirm that filament extension occurs in the 5' to 3' direction on
      single-stranded DNA. These filaments also disassemble in an end-dependent
      fashion, and several indirect observations suggest that the disassembly occurs on
      the end opposite to that at which assembly occurs. By labeling the 5' end of
      single-stranded DNA with a segment of duplex DNA, we demonstrate unambiguously
      that RecA filaments disassemble uniquely in the 5' to 3' direction.

PMID- 11574551
TI  - Taxonomy and identification of the Burkholderia cepacia complex.

PMID- 11574552
TI  - Widespread occurrence of Pneumocystis carinii in commercial rat colonies detected
      using targeted PCR and oral swabs.
AB  - The genus Pneumocystis contains a family of fungal organisms that infect a wide
      variety of mammalian species. Although it is a cause of pneumonia in
      immunocompromised hosts, recent evidence suggests that these organisms colonize
      nonimmunosuppressed hosts. Detection of cryptic colonization with Pneumocystis
      becomes important in animal studies when infection-free animals are necessary.
      Provocation by chronic immunosuppression, histology, and serology has been widely
      used to detect the presence of Pneumocystis in rat colonies, requiring lengthy
      time periods and/or postmortem tissue. We conducted a study to evaluate the use
      of PCR amplification of oral swabs for the antemortem detection of Pneumocystis
      in 12 rat groups from three commercial vendors. Sera were collected upon arrival,
      and the oral cavity was swabbed for PCR analysis. Ten of these groups of rats
      were then housed in pairs under barrier and immunosuppressed to provoke
      Pneumocystis growth. Once moribund, the rats were sacrificed, and the lungs were
      collected to evaluate the presence of Pneumocystis by PCR and microscopic
      enumeration. DNA was extracted from oral swabs and lung homogenates, and PCR was
      performed using primers targeting a region within the mitochondrial large-subunit
      rRNA of Pneumocystis carinii f. sp. carinii. Upon receipt, 64% of rats were
      positive for P. carinii f. sp. carinii-specific antibodies, while P. carinii f.
      sp. carinii DNA was amplified from 98% of oral swabs. Postmortem PCR analysis of
      individual lungs revealed P. carinii f. sp. carinii DNA in all rat lungs,
      illustrating widespread occurrence of Pneumocystis in commercial rat colonies.
      Thus, oral swab/PCR is a rapid, nonlethal, and sensitive method for the
      assessment of Pneumocystis exposure.

PMID- 11574553
TI  - Epidemiological validation of pulsed-field gel electrophoresis patterns for
      methicillin-resistant Staphylococcus aureus.
AB  - To determine the stability of pulsed-field gel electrophoresis (PFGE) patterns of
      methicillin-resistant Staphylococcus aureus in the nosocomial setting, we
      analyzed isolates from long-term carriers (>1 month) and from patients involved
      in well-defined nosocomial epidemics. The number of fragment differences between
      the first isolate and subsequent isolates in long-term carriers showed a bimodal
      distribution, with one group having 0 to 6 fragment differences and the other
      group having 14 to 24 fragment differences. The PFGE patterns of isolates
      involved in epidemics also presented a similar bimodal distribution of the number
      of fragment differences. Typing these isolates with another molecular method
      (inter-IS256 PCR) showed that isolates of the first group (i.e., with 1 to 6
      fragment differences) were clonally related, whereas the second group (with 14 to
      24 fragment differences) could be considered genetically different. Among long
      term carriers with clonally related isolates, 74 of 84 (88%) of consecutive
      isolates showed indistinguishable patterns, whereas 10 of 84 (12%) showed related
      patterns differing by one to six fragments. Moreover, the frequency of apparition
      of related patterns is higher when the time between the first and the subsequent
      isolate is longer. During seven nosocomial epidemics lasting from 1 to 15 months,
      only 2 of 120 isolates (1.7%) showed a pattern which was different, although
      related, from the predominant one involved in each of these outbreaks.

PMID- 11574554
TI  - Sensitive and specific method for rapid identification of Streptococcus
      pneumoniae using real-time fluorescence PCR.
AB  - Molecular surveillance of pathogens has shown the need for rapid and dependable
      methods for the identification of organisms of clinical and epidemiological
      importance. As the leading cause of community-acquired pneumonia, Streptococcus
      pneumoniae was used as a model organism to develop and refine a real-time
      fluorescence PCR assay and enhanced DNA purification method. Seventy clinical
      isolates of S. pneumoniae, verified by latex agglutination, were screened against
      26 negative control clinical isolates employing a TaqMan assay on a thermocycler
      (LightCycler). The probe, constructed from the lytA gene, correctly detected all
      S. pneumoniae genomes without cross-reaction to negative controls. The speed and
      ease of this approach will make it adaptable to identification of many bacterial
      pathogens and provide potential for adaptation to direct detection from patient
      specimens.

PMID- 11574555
TI  - Molecular analysis of a hospital cafeteria-associated salmonellosis outbreak
      using modified repetitive element PCR fingerprinting.
AB  - A hospital cafeteria-associated outbreak of gastroenteritis due to Salmonella
      enterica serotype Infantis was retrospectively evaluated using modified
      repetitive element PCR (rep-PCR) fingerprinting with the ERIC2 and BOXA1R primers
      and computer-assisted gel analysis and dendrogram construction. Rep-PCR yielded
      objective between-cycler, same-strain similarity values of from 92% (composite
      fingerprints) to 96% (ERIC2 fingerprints). The 70 Salmonella isolates (which
      included 19 serotype Infantis isolates from the hospital outbreak, 10 other
      serotype Infantis isolates, and 41 isolates representing 14 other serotypes) were
      resolved well to the serotype level with each of the three fingerprint types
      (ERIC2, BOXA1R, and composite). Rep-PCR typing uncovered several historical
      serotyping errors and provided presumptive serotype assignments for other
      isolates with incomplete or undetermined serotypes. Analysis of replicate
      fingerprints for each isolate, as generated on two different thermal cyclers,
      indicated that most of the seeming subserotype discrimination noted in single
      cycler dendrograms actually represented assay variability, since it was not
      reproducible in combined-cycler dendrograms. Rep-PCR typing, which would have
      been able to identify the presence of the hospital-associated serotype Infantis
      outbreak after the second outbreak isolate, could be used as a simple surrogate
      for serotyping by clinical microbiology laboratories that are equipped for
      diagnostic PCR.

PMID- 11574556
TI  - Multistate outbreak of Salmonella serovar Muenchen infections associated with
      alfalfa sprouts grown from seeds pretreated with calcium hypochlorite.
AB  - During September 1999, a multistate outbreak of Salmonella serovar Muenchen
      infection associated with eating raw alfalfa sprouts was identified in Wisconsin.
      Despite use of a calcium hypochlorite sanitizing procedure to pretreat seeds
      before sprouting, at least 157 outbreak-related illnesses were identified in
      seven states having sprouters who received alfalfa seed from a specific lot. The
      continued occurrence of sprout-related outbreaks despite presprouting
      disinfection supports the concern that no available treatment will eliminate
      pathogens from seeds before sprouting and reinforces the need for additional
      safeguards to protect the public. A lack of consumer knowledge regarding exposure
      to sprouts documented in this investigation suggests that more-targeted outreach
      to high-risk individuals may be needed to reduce their risk.

PMID- 11574557
TI  - Rapid identification of yeasts in positive blood cultures by a multiplex PCR
      method.
AB  - Yeasts are emerging as important etiological agents of nosocomial bloodstream
      infections. A multiplex PCR method was developed to rapidly identify clinically
      important yeasts that cause fungemia. The method amplified the internal
      transcribed spacer 1 (ITS1) region between the 18S and 5.8S rRNA genes and a
      specific DNA fragment within the ITS2 region of Candida albicans. With this
      method, C. albicans produced two amplicons, whereas other species produced only
      one. Through sequence analysis, the precise lengths of the PCR products were
      found to be as follows: C. glabrata (482 or 483 bp), C. guilliermondii (248 bp),
      C. parapsilosis (229 bp), C. albicans (218 or 219 and 110 bp), C. tropicalis (218
      bp), Cryptococcus neoformans (201 bp), and C. krusei (182 bp). The PCR products
      could be effectively separated by disk polyacrylamide gel electrophoresis. The
      method was used to test 249 positive blood cultures (255 isolates), from which
      the following species (strain number) were isolated: C. albicans (128), C.
      tropicalis (51), C. glabrata (28), C. parapsilosis (23), C. neoformans (9), C.
      krusei (5), C. guilliermondii (3), and other, minor species (8). The test
      sensitivity of the method was 96.9% (247 of 255 isolates). The eight minor
      species were either misidentified (one strain) or not identified (seven strains).
      From the time at which a positive bottle was found, the multiplex PCR could be
      completed within 8 h; the present method is simpler than any previously reported
      molecular method for the identification of blood yeasts.

PMID- 11574558
TI  - Molecular characterization of Cryptosporidium isolates obtained from humans in
      France.
AB  - Cryptosporidium parvum is usually considered the agent of human
      cryptosporidiosis. However, only in the last few years, molecular biology-based
      methods have allowed the identification of Cryptosporidium species and genotypes,
      and only a few data are available from France. In the present work, we collected
      samples of whole feces from 57 patients from France (11 immunocompetent patients,
      35 human immunodeficiency virus [HIV]-infected patients, 11 immunocompromised but
      non-HIV-infected patients) in whom Cryptosporidium oocysts were recognized by
      clinical laboratories. A fragment of the Cryptosporidium 18S rRNA gene
      encompassing the hypervariable region was amplified by PCR and sequenced. The
      results revealed that the majority of the patients were infected with cattle (29
      of 57) or human (18 of 57) genotypes of Cryptosporidium parvum. However, a number
      of immunocompromised patients were infected with C. meleagridis (3 of 57), C.
      felis (6 of 57), or a new genotype of C. muris (1 of 57). This is the first
      report of the last three species of Cryptosporidium in humans in France. These
      results indicate that immunocompromised individuals are susceptible to a wide
      range of Cryptosporidium species and genotypes.

PMID- 11574559
TI  - Development of a Canadian standardized protocol for subtyping methicillin
      resistant Staphylococcus aureus using pulsed-field gel electrophoresis.
AB  - A panel of 24 methicillin-resistant Staphylococcus aureus strains was distributed
      to 15 laboratories in Canada to evaluate their in-house pulsed-field gel
      electrophoresis (PFGE) protocols and interpretation criteria. Attempts to compare
      fingerprint images using computer-aided analysis were not successful due to
      variability in individual laboratory PFGE protocols. In addition, individual site
      interpretation of the fingerprint patterns was inadequate, as 7 of 13 sites (54%)
      made at least one error in interpreting the fingerprints from the panel. A 2-day
      standardized PFGE protocol (culture to gel image) was developed and distributed
      to all of the sites. Each site was requested to use the standardized protocol on
      five strains from the original panel. Thirteen sites submitted gel images for
      comparisons. The protocol demonstrated excellent reproducibility and allowed
      interlaboratory comparisons with Molecular Analyst DST software (Bio-Rad) and
      1.5% band tolerance.

PMID- 11574560
TI  - Molecular analysis of Malassezia microflora on the skin of atopic dermatitis
      patients and healthy subjects.
AB  - Members of the genus Malassezia, lipophilic yeasts, are considered to be one of
      the exacerbating factors in atopic dermatitis (AD). We examined variation in
      cutaneous colonization by Malassezia species in AD patients and compared it with
      variation in healthy subjects. Samples were collected by applying transparent
      dressings to the skin lesions of AD patients. DNA was extracted directly from the
      dressings and amplified in a specific nested PCR assay. Malassezia-specific DNA
      was detected in all samples obtained from 32 AD patients. In particular,
      Malassezia globosa and M. restricta were detected in approximately 90% of the AD
      patients and M. furfur and M. sympodialis were detected in approximately 40% of
      the cases. The detection rate was not dependent on the type of skin lesion. In
      healthy subjects, Malassezia DNA was detected in 78% of the samples, among which
      M. globosa, M. restricta, and M. sympodialis were detected at frequencies ranging
      from 44 to 61%, with M. furfur at 11%. The diversity of Malassezia species found
      in AD patients was greater (2.7 species detected in each individual) than that
      found in healthy subjects (1.8 species per individual). Our results suggest that
      M. furfur, M. globosa, M. restricta, and M. sympodialis are common inhabitants of
      the skin of both AD patients and healthy subjects, while the skin microflora of
      AD patients shows more diversity than that of healthy subjects. To our knowledge,
      this is the first report of the use of a nested PCR as an alternative to fungal
      culture for analysis of the distribution of cutaneous Malassezia spp.

PMID- 11574561
TI  - Quantification of Candida albicans actin mRNA by the LightCycler system as a
      means of assessing viability in a model of cutaneous candidiasis.
AB  - The LightCycler system (two-step reverse transcription-PCR-fluorescent
      hybridization [LC RT-PCR-FH]) was used to quantify Candida albicans actin mRNA as
      a means of assessing its viability in a reconstituted skin model of cutaneous
      candidiasis following the application of an antimycotic. A 192-bp ACT exon
      fragment was ligated into the pCR2.1 plasmid vector, and dilutions of the cloned
      insert (pACT; 4.092 kb) were used as the standard reference template. The LC RT
      PCR-FH system could detect 1 fg of pACT, equivalent to 2.2 copies of the plasmid.
      The ACT exon-based PCR primers and FH probes were C. albicans specific, and
      electrophoretic analysis of the LC RT-PCR-FH assay product showed a 174-bp band
      in agarose gel. The number of copies of C. albicans ACT mRNA per milligram of
      tissue decreased with increasing amounts of amorolfine applied to a C. albicans
      infected skin model, showing a reduction in viability. Detection and
      quantification of ACT mRNA in tissue by the LC RT-PCR-FH assay corresponded with
      cultural isolation of C. albicans from samples. The ACT mRNA-targeted LC RT-PCR
      FH assay represents a sensitive, specific, rapid, and quantitative means of
      assessing the viability of C. albicans in infected tissue. This method may also
      be useful in evaluating the therapeutic efficacies of antifungal drugs in the
      treatment of various forms of candidiasis and other fungal diseases.

PMID- 11574562
TI  - Evaluation of a rapid immunochromatographic test for detection of Streptococcus
      pneumoniae antigen in urine samples from adults with community-acquired
      pneumonia.
AB  - Streptococcus pneumoniae is the most common cause of community-acquired pneumonia
      but is undoubtedly underdiagnosed. Isolation of S. pneumoniae from blood is
      specific but lacks sensitivity, while isolation of S. pneumoniae from sputum may
      represent colonization. We evaluated a new immunochromatographic test (NOW S.
      pneumoniae urinary antigen test; Binax, Portland, Maine) that is simple to
      perform and that can detect S. pneumoniae antigen in urine within 15 min. Urine
      samples from 420 adults with community-acquired pneumonia and 169 control
      patients who did not have pneumonia were tested. Urine from 315 (75%) of the
      pneumonia patients and all controls was tested both before and after 25-fold
      concentration, while the remaining 105 samples were only tested without
      concentration. S. pneumoniae urinary antigen tests were positive for 120 (29%)
      patients with pneumonia and for none of the controls. Of the urine samples tested
      with and without concentration, 96 were positive, of which 6 were positive only
      after concentration. S. pneumoniae antigen was detected in the urine from 16 of
      the 20 (80%) patients with blood cultures positive for S. pneumoniae and from 28
      of the 54 (52%) patients with sputum cultures positive for S. pneumoniae. The
      absence of S. pneumoniae antigen in the urine from controls suggests that the
      specificity is high. Concentration of urine prior to testing resulted in a small
      increase in yield. The NOW S. pneumoniae urinary antigen test should be a useful
      adjunct to culture for determining the etiology of community-acquired pneumonia
      in adults.

PMID- 11574563
TI  - Phospholipase region of Mycobacterium tuberculosis is a preferential locus for
      IS6110 transposition.
AB  - Enzymes with phospholipase C activity in Mycobacterium tuberculosis have been
      recently described. The three genes encoding these proteins, plcA, plcB, and
      plcC, are located at position 2351 of the genomic map of M. tuberculosis H37Rv
      and are arranged in tandem. We have previously described the presence of
      variations in the restriction fragment length polymorphism patterns of the plcA
      and plcB genes in M. tuberculosis clinical isolates. In the present work we
      investigated the origin of this polymorphism by sequence analysis of the
      phospholipase-encoding regions of 11 polymorphic M. tuberculosis clinical
      isolates. To do so, a long-PCR assay was used to amplify a 5,131-bp fragment that
      contains the plcA and plcB genes and part of the plcC gene. In the M.
      tuberculosis strains studied the production of an amplicon approximately 1,400 bp
      larger than anticipated was observed. Sequence analysis of the PCR products
      indicated the presence of a foreign sequence that corresponded to an IS6110
      element. We observed insertion elements in the plcA, plcB, and plcC genes. One
      site in plcB had the highest incidence of transposition (5 out of 11 strains). In
      two strains the insertion element was found in plcA in the same nucleotide
      position. In all the cases, IS6110 was transposed in the same direction. The high
      level of transposition in the phospholipase region can lead to the excision of
      fragments of genomic DNA by recombination of neighboring IS6110 elements, as
      demonstrated by finding the deletion, in two strains, of a 2,837-bp fragment that
      included plcA and most of plcB. This can explain the negative results obtained by
      some authors when detecting the mtp40 sequence (plcA) by PCR. Given the high
      polymorphism in this region, the use of the mtp40 sequence as a genetic marker
      for M. tuberculosis sensu stricto is very restricted.

PMID- 11574564
TI  - Rapid identification of dimorphic and yeast-like fungal pathogens using specific
      DNA probes.
AB  - Specific oligonucleotide probes were developed to identify medically important
      fungi that display yeast-like morphology in vivo. Universal fungal primers ITS1
      and ITS4, directed to the conserved regions of ribosomal DNA, were used to
      amplify DNA from Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides
      immitis, Paracoccidioides brasiliensis, Penicillium marneffei, Sporothrix
      schenckii, Cryptococcus neoformans, five Candida species, and Pneumocystis
      carinii. Specific oligonucleotide probes to identify these fungi, as well as a
      probe to detect all dimorphic, systemic pathogens, were developed. PCR amplicons
      were detected colorimetrically in an enzyme immunoassay format. The dimorphic
      probe hybridized with DNA from H. capsulatum, B. dermatitidis, C. immitis, P.
      brasiliensis, and P. marneffei but not with DNA from nondimorphic fungi. Specific
      probes for H. capsulatum, B. dermatitidis, C. immitis, P. brasiliensis, P.
      marneffei, S. schenckii, C. neoformans, and P. carinii hybridized with homologous
      but not heterologous DNA. Minor cross-reactivity was observed for the B.
      dermititidis probe used against C. immitis DNA and for the H. capsulatum probe
      used against Candida albicans DNA. However, the C. immitis probe did not cross
      react with B. dermititidis DNA, nor did the dimorphic probe hybridize with C.
      albicans DNA. Therefore, these fungi could be differentiated by a process of
      elimination. In conclusion, probes developed to yeast-like pathogens were found
      to be highly specific and should prove to be useful in differentiating these
      organisms in the clinical setting.

PMID- 11574565
TI  - Characterization of newly emerging Newcastle disease virus isolates from the
      People's Republic of China and Taiwan.
AB  - Seven Newcastle disease (ND) virus (NDV) isolates which were recovered from ND
      outbreaks in chicken and pigeon flocks in China and Taiwan between 1996 and 2000
      were genotypically and pathotypically characterized. By phylogenetic analysis of
      the fusion protein genes, isolates Ch-A7/96, Ch/98-3, Ch/99, Ch/2000, and TW/2000
      were placed into two novel subgenotypes, VIIc and VIId. Isolate Ch/98-1 was
      grouped into subgenotype VIb, while Ch-W6/96 was proven to be a mixture of
      isolates Ch-A7/96 and Ch/98-1. These isolates were pathotyped as viscerotropic
      velogenic for Ch/98-3, Ch/99, Ch/2000, and TW/2000; neurotropic velogenic for Ch
      A7/96; and mesogenic for Ch/98-1. Three separate, comparative, genetic analyses
      of the F genes, including genetic distance measurement, phylogenetic tree
      analysis, and residue substitution analysis, were performed with our isolates and
      selected NDV strains from GenBank. Results showed that the close genetic
      similarity provided evidence for the epidemiological linkage between the
      outbreaks in China and Taiwan and that the 1990s outbreaks in Asia, the Middle
      East, Africa, and Europe constituted the fourth panzootic of ND. In combination
      with epidemiological analysis, an evolutionary model of the NDV strains,
      representative of the direction of transmission within the NDV strains, was
      proposed, and epidemiology of NDV transmission was evaluated with emphasis on
      molecular aspects. Finally, a cross-protective experiment indicated that at least
      one strain (Ch-A7/96) among our NDV isolates was an antigenic variant,
      responsible for recent outbreaks of ND in vaccinated chicken flocks.

PMID- 11574566
TI  - Granulicatella and Abiotrophia species from human clinical specimens.
AB  - One hundred one isolates of nutritionally variant streptococci from 97 patients
      were phenotypically characterized and compared with the type strains of
      Granulicatella adiacens (formerly Abiotrophia adiacens) (ATCC 49175(T))
      Abiotrophia defectiva (ATCC 49176(T)), and Granulicatella elegans (formerly
      Abiotrophia elegans) (DSM 11693(T)). Of the isolates, 55 and 43 resembled G.
      adiacens and A. defectiva, respectively, while 3 strains resembled G. elegans.
      Phenotypic characteristics useful in differentiating between species within the
      genera Granulicatella and Abiotrophia (G. adiacens, G. elegans, Granulicatella
      balaenopterae, and A. defectiva) were production of alpha- and beta
      galactosidase; production of beta-glucuronidase; hippurate hydrolysis; arginine
      dihydrolase activity; and acid production from trehalose, sucrose, pullulan, and
      tagatose. From the reports submitted with the specimens, the clinical diagnosis
      was endocarditis in 58% of patients and septicemia or bacteremia in 26% of
      patients.

PMID- 11574567
TI  - Great diversity of group A rotavirus strains and high prevalence of mixed
      rotavirus infections in India.
AB  - We previously observed a marked diversity of rotavirus strains and a high
      prevalence of the uncommon serotype G9 in a small survey of rotavirus strains
      collected from six centers in India. In the present study, we characterized a
      larger collection of strains from children hospitalized with severe diarrhea in
      seven Indian cities between 1996 and 1998. A total of 287 strains were G and P
      genotyped by reverse transcription-PCR, and some were further characterized by
      electropherotyping and subgrouping. Of the four strains common globally, three
      were found in only 43% of samples (P[8], G1, 15%; P[4], G2, 22%; P[8], G4, 6%),
      whereas G9 strains made up 17% of the total. Three different G9 strains were
      present: a P[8], G9 strain, which displayed the long electropherotype and
      subgroup II VP6 specificity, and two P[6], G9 strains, one with the long
      electropherotype and subgroup II specificity and the other with the short
      electropherotype and subgroup I specificity. Marked diversity was observed among
      strains collected from different cities and collected over time. Of the 253
      strains that were fully typed, 54 (21%) had a mixed G or P genotype. Serotype G2
      strains were detected more often in infections caused by single strains than in
      mixed infections (P < 0.05), whereas serotype G1 strains were found more often in
      mixed infections than in infections caused by single strains (P < 0.05). The
      diversity of rotavirus strains and the high prevalence of mixed infections
      confirm trends reported earlier and help to better characterize the strains of
      rotavirus circulating in India. Vaccines under development should clearly target
      G9 strains, and G9 should be included as one of the common global serotypes.

PMID- 11574568
TI  - Nonisotopic detection of human papillomavirus DNA in clinical specimens using a
      consensus PCR and a generic probe mix in an enzyme-linked immunosorbent assay
      format.
AB  - We assessed the value of a new digoxigenin (DIG)-labeled generic probe mix in a
      PCR-enzyme-linked immunosorbent assay format to screen for the presence of human
      papillomavirus (HPV) DNA amplified from clinical specimens. After screening with
      this new generic assay is performed, HPV DNA-positive samples can be directly
      genotyped using a reverse blotting method with product from the same PCR
      amplification. DNA from 287 genital specimens was amplified via PCR using biotin
      labeled consensus primers directed to the L1 gene. HPV amplicons were captured on
      a streptavidin-coated microwell plate (MWP) and detected with a DIG-labeled HPV
      generic probe mix consisting of nested L1 fragments from types 11, 16, 18, and
      51. Coamplification and detection of human DNA with biotinylated beta-globin
      primers served as a control for both sample adequacy and PCR amplification. All
      specimens were genotyped using a reverse line blot assay (13). Results for the
      generic assay using MWPs and a DIG-labeled HPV generic probe mix (DIG-MWP generic
      probe assay) were compared with results from a previous analysis using dot blots
      with a radiolabeled nested generic probe mix and type-specific probes for
      genotyping. The DIG-MWP generic probe assay resulted in high intralaboratory
      concordance in genotyping results (88% versus 73% agreement using traditional
      methods). There were 207 HPV-positive results using the DIG-MWP method and 196
      positives using the radiolabeled generic probe technique, suggesting slightly
      improved sensitivity. Only one sample failed to test positive with the DIG-MWP
      generic probe assay in spite of a positive genotyping result. Concordance between
      the two laboratories was nearly 87%. Approximately 6% of samples that were
      positive or borderline when tested with the DIG-MWP generic probe assay were not
      detected with the HPV type-specific panel, perhaps representing very rare or
      novel HPV types. This new method is easier to perform than traditional generic
      probe techniques and uses more objective interpretation criteria, making it
      useful in studies of HPV natural history.

PMID- 11574569
TI  - Quantitative, fluorogenic probe PCR assay for detection of human herpesvirus 8
      DNA in clinical specimens.
AB  - A quantitative, fluorescence-based PCR assay (TaqMan-based system) was developed
      for detection of human herpesvirus 8 (HHV-8) DNA in clinical specimens. Primers
      and probes chosen from each of five 10-kb segments from the unique region of the
      HHV-8 genome were evaluated for sensitivity with dilution series of DNA extracted
      from a cell line (BCBL-1) that harbors HHV-8 DNA. Although several of the primer
      probe sets performed similarly with BCBL-1 DNA that had been diluted in water,
      their performance differed when target DNA was diluted in a constant background
      of uninfected cell DNA, an environment more relevant to their intended use. The
      two best primer-probe combinations were specific for HHV-8 relative to the other
      known human herpesviruses and herpesvirus saimiri, a closely related
      gammaherpesvirus of nonhuman primates. PCRs included an enzymatic digestion step
      to eliminate PCR carryover and an exogenous internal positive control that
      enabled discrimination of false-negative from true-negative reactions. The new
      assays were compared to conventional PCR assays for clinical specimens (saliva,
      rectal brushings, rectal swab specimens, peripheral blood lymphocytes, semen, and
      urine) from human immunodeficiency virus-positive patients with or without
      Kaposi's sarcoma. In all instances, the new assays agreed with each other and
      with the conventional PCR system. In addition, the quantitative results obtained
      with the new assays were in good agreement both for duplicate reactions in the
      same assay and between assays.

PMID- 11574570
TI  - Geographical heterogeneity between Far Eastern and Western countries in
      prevalence of the virulence plasmid, the superantigen Yersinia pseudotuberculosis
      derived mitogen, and the high-pathogenicity island among Yersinia
      pseudotuberculosis strains.
AB  - Yersinia pseudotuberculosis produces novel superantigenic toxins designated YPMa
      (Y. pseudotuberculosis-derived mitogen), YPMb, and YPMc and has a pathogenicity
      island termed HPI (high-pathogenicity island) and R-HPI (the right-hand part of
      the HPI with truncation in its left-hand part) on the chromosome. Analysis of the
      distribution of these virulence factors allowed for differentiation of species Y.
      pseudotuberculosis into six subgroups, thus reflecting the geographical spread of
      two main clones: the YPMa(+) HPI(-) Far Eastern systemic pathogenic type
      belonging to serotypes O1b, -2a, -2b, -2c, -3, -4a, -4b, -5a, -5b, -6, -10, and
      UT (untypeable) and the YPMs(-) HPI(+) European gastroenteric pathogenic type
      belonging to serotypes O1a and -1b. The YPMa(+) HPI(+) pathogenic type belonging
      to serotypes O1b, -3, -5a, -5b, and UT and the YPMb(+) HPI(-) nonpathogenic type
      belonging to non-melibiose-fermenting serotypes O1b, -5a, -5b, -6, -7, -9, -10, 
      11, and -12 were prevalent in the Far East. The YPMc(+) R-HPI(+) European low
      pathogenicity type belonging to non-melibiose-fermenting serotype O3 and the
      YPMs(-) HPI(-) pathogenic type belonging to 15 serotypes were found to be
      prevalent all over the world. This new information is useful for a better
      understanding of the evolution and spread of Y. pseudotuberculosis.

PMID- 11574571
TI  - Aortic valve endocarditis in a dog due to Bartonella clarridgeiae.
AB  - We report the first documented case of endocarditis associated with Bartonella
      clarridgeiae in any species. B. clarridgeiae was identified as a possible
      etiological agent of human cat scratch disease. Infective vegetative valvular
      aortic endocarditis was diagnosed in a 2.5-year-old male neutered boxer.
      Historically, the dog had been diagnosed with a systolic murmur at 16 months of
      age and underwent balloon valvuloplasty for severe valvular aortic stenosis. Six
      months later, the dog was brought to a veterinary hospital with an acute third
      degree atrioventricular block and was diagnosed with infective endocarditis. The
      dog died of cardiopulmonary arrest prior to pacemaker implantation. Necropsy
      confirmed severe aortic vegetative endocarditis. Blood culture grew a fastidious,
      gram-negative organism 8 days after being plated. Phenotypic and genotypic
      characterization of the isolate, including partial sequencing of the citrate
      synthase (gltA) and 16S rRNA genes indicated that this organism was B.
      clarridgeiae. DNA extraction from the deformed aortic valve and the healthy
      pulmonic valve revealed the presence of B. clarridgeiae DNA only from the
      diseased valve. No Borrelia burgdorferi or Ehrlichia sp. DNA could be identified.
      Using indirect immunofluorescence tests, the dog was seropositive for B.
      clarridgeiae and had antibodies against Ehrlichia phagocytophila but not against
      Ehrlichia canis, Ehrlichia ewingii, B. burgdorferi, or Coxiella burnetii.

PMID- 11574572
TI  - Identification of clinical isolates of actinomyces species by amplified 16S
      ribosomal DNA restriction analysis.
AB  - Amplified 16S ribosomal DNA (rDNA) restriction analysis (ARDRA), using enzymes
      HaeIII and HpaII, was applied to 176 fresh and 299 stored clinical isolates of
      putative Actinomyces spp. referred to the Anaerobe Reference Unit of the Public
      Health Laboratory Service for confirmation of identity. Results were compared
      with ARDRA results obtained previously for reference strains and with
      conventional phenotypic reactions. Identities of some strains were confirmed by
      analysis of partial 16S rDNA sequences. Of the 475 isolates, 331 (70%) were
      clearly assigned to recognized Actinomyces species, including 94 isolates
      assigned to six recently described species. A further 52 isolates in 12 ARDRA
      profiles were designated as apparently resembling recognized species, and 44
      isolates, in 18 novel profiles, were confirmed as members of genera other than
      Actinomyces. The identities of 48 isolates in nine profiles remain uncertain, and
      they may represent novel species of Actinomyces. For the majority of species,
      phenotypic results, published reactions for the species, and ARDRA profiles
      concurred. However, of 113 stored isolates originally identified as A. meyeri or
      resembling A. meyeri by phenotypic tests, only 21 were confirmed as A. meyeri by
      ARDRA; 63 were reassigned as A. turicensis, 7 as other recognized species, and 22
      as unidentified actinomycetes. Analyses of incidence and clinical associations of
      Actinomyces spp. add to the currently sparse knowledge of some recently described
      species.

PMID- 11574573
TI  - Automated high-throughput genotyping for study of global epidemiology of
      Mycobacterium tuberculosis based on mycobacterial interspersed repetitive units.
AB  - Large-scale genotyping of Mycobacterium tuberculosis is especially challenging,
      as the current typing methods are labor-intensive and the results are difficult
      to compare among laboratories. Here, automated typing based on variable-number
      tandem repeats (VNTRs) of genetic elements named mycobacterial interspersed
      repetitive units (MIRUs) in 12 mammalian minisatellite-like loci of M.
      tuberculosis is presented. This system combines analysis of multiplex PCRs on a
      fluorescence-based DNA analyzer with computerized automation of the genotyping.
      Analysis of a blinded reference set of 90 strains from 38 countries (K. Kremer et
      al., J. Clin. Microbiol. 37:2607-2618, 1999) demonstrated that it is 100%
      reproducible, sensitive, and specific for M. tuberculosis complex isolates, a
      performance that has not been achieved by any other typing method tested in the
      same conditions. MIRU-VNTRs can be used for analysis of the global genetic
      diversity of M. tuberculosis complex strains at different levels of evolutionary
      divergence. To fully exploit the portability of this typing system, a website was
      set up for the analysis of M. tuberculosis MIRU-VNTR genotypes via the Internet.
      This opens the way for global epidemiological surveillance of tuberculosis and
      should lead to novel insights into the evolutionary and population genetics of
      this major pathogen.

PMID- 11574574
TI  - Detection of antibodies to a disease-associated herpesvirus of the green turtle,
      Chelonia mydas.
AB  - Lung-eye-trachea disease-associated herpesvirus (LETV) is linked with morbidity
      and mortality in mariculture-reared green turtles, but its prevalence among and
      impact on wild marine turtle populations is unknown. An enzyme-linked
      immunosorbent assay (ELISA) was developed for detection of anti-LETV antibodies
      and could distinguish LETV-exposed green turtles from those with antibodies to
      fibropapillomatosis-associated herpesvirus (FPHV). Plasma from two captive-reared
      green turtles immunized with inactivated LETV served as positive controls. Plasma
      from 42 healthy captive-reared green turtles and plasma from 30 captive-reared
      green turtles with experimentally induced fibropapillomatosis (FP) and anti-FPHV
      antibodies had low ELISA values on LETV antigen. A survey of 19 wild green
      turtles with and 27 without FP (with and without anti-FPHV antibodies,
      respectively) identified individuals with antibodies to LETV regardless of their
      FP status. The seroprevalence of LETV infection was 13%. The presence of
      antibodies to LETV in plasma samples was confirmed by Western blot and
      immunohistochemical analyses. These results are the first to suggest that wild
      Florida green turtles are exposed to LETV or to an antigenically closely related
      herpesvirus(es) other than FPHV and that FPHV and LETV infections are most likely
      independent events. This is the first ELISA developed to detect antibodies for a
      specific herpesvirus infection of marine turtles. The specificity of this ELISA
      for LETV (ability to distinguish LETV from FPHV) makes it valuable for detecting
      exposure to this specific herpesvirus and enhances our ability to conduct
      seroepidemiological studies of these disease-associated agents in marine turtles.

PMID- 11574575
TI  - Direct identification of bacteria from positive blood cultures by amplification
      and sequencing of the 16S rRNA gene: evaluation of BACTEC 9240 instrument true
      positive and false-positive results.
AB  - In a previous study which evaluated the BACTEC 9240 automated blood culture
      system (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.), we noted a
      1.3% "instrument false-positive" rate. That is, the BACTEC system signaled that a
      bottle (BACTEC Plus Aerobic/F bottle or BACTEC Anaerobic Lytic/10 bottle) culture
      was positive but a Gram stain was negative and there was no growth of bacteria or
      yeasts on subculture to chocolate agar. Furthermore, from the same sample of
      blood, cultures for fungi using the Isolator blood culture system (Wampole
      Laboratories, Cranbury, N.J.) were negative for growth. For the present study, we
      evaluated 76 instrument false-positive samples for the presence of 16S ribosomal
      DNA using the MicroSeq 500 kit (PE Biosystems, Foster City, Calif.). These
      samples also were negative for fungi by the Isolator method. This kit has a PCR
      module and sequencing module for the amplification and sequencing of the 16S RNA
      gene and provides a database for sequence alignment and identification of
      bacteria. To optimize the assay, we evaluated the effect of adding 0.5% bovine
      serum albumin to the sample from blood culture bottles and found that it
      decreased the effects of inhibitors on the PCR. Two control groups of blood
      culture specimens were also evaluated. One group (n = 45) were "instrument true
      positives"; the instrument signaled positive, and subsequent Gram stains were
      positive and subcultures on chocolate agar grew bacteria. The other group (n =
      20) were "instrument true negatives"; the instrument signaled negative, the Gram
      stain was negative, and subcultures on chocolate agar and from the Isolator tube
      on fungal media showed no growth. None of the 76 instrument false-positive
      samples had evidence for 16S rRNA gene sequences. All of the instrument true
      positive samples and all of the instrument true-negative specimens were positive
      and negative, respectively, using the MicroSeq 500 kit. Total peripheral white
      blood cell counts were statistically significantly higher for patients who had
      instrument false-positive results than for patients who had instrument true
      positive or true-negative results (P = 0.001). We conclude that instrument false
      positives signaled by the BACTEC 9240 system are not due to bacteria in the blood
      culture samples.

PMID- 11574576
TI  - Rapid identification and antibiotic susceptibility testing of Salmonella enterica
      serovar Typhi isolated from blood: implications for therapy.
AB  - The turnaround time (TAT) for Salmonella enterica serovar Typhi identification
      and reporting of the antibiotic susceptibility profile was determined for 391
      cases of typhoid fever, using the lysis direct plating or lysis centrifugation
      method of blood culture along with rapid antimicrobial susceptibility testing.
      The TAT was more rapid (TAT for 90% of the patients [TAT(90)] = 30 h; TAT(100)
      </= 67 h) than was possible with conventional methodologies and was equivalent to
      that reported previously using more advanced, costly technologies that are
      largely unavailable in developing countries. Antibiotic susceptibility profiles,
      determined by the rapid antimicrobial susceptibility testing method, of randomly
      selected 60 S. enterica serovar Typhi isolates were identical to those determined
      by overnight conventional testing. Preliminary assessment of the impact of the
      reduced TAT on physician practices revealed that initial empirical therapy was
      prescribed at the time of presentation in most cases (87 of 108 [81%]) despite
      awareness that the final report would be available on the following day. Patients
      treated empirically with first-line antibiotics and shown subsequently to be
      infected with a multidrug-resistant strain benefited most (8 cases), since
      therapy was changed appropriately on the following day. In an additional 21
      cases, therapy with an appropriate antibiotic was initiated after culture results
      were available. Thus, in approximately one-fourth (29 of 108 [27%]) of the cases,
      a change in management to an agent active for treatment of the isolate was made
      after receipt of the test results. However, in no case was therapy changed from a
      second-line to a first-line agent, even if the isolate was reported on the day
      after presentation to be sensitive to first-line therapy (33 cases). Ways in
      which to utilize rapid-TAT result reporting in order to positively influence
      physicians' prescribing in Bangladesh are the subject of ongoing research.

PMID- 11574577
TI  - Methicillin-resistant, quinupristin-dalfopristin-resistant Staphylococcus aureus
      with reduced sensitivity to glycopeptides.
AB  - Of 3,052 Staphylococcus aureus strains collected by the European SENTRY
      surveillance study, 35 were found to be nonsusceptible to quinupristin
      dalfopristin (MIC of > or =2 mg/liter). These isolates originated from four
      hospitals in France and one in Spain. In isolates from two Parisian hospitals
      exhibiting the same SmaI macrorestriction pattern, streptogramin resistance was
      based on vatA and vgbA. One isolate from a hospital in Lyon and 22 from a
      hospital in Lille were of the vatB vgaB streptogramin A resistance genotype and
      possessed ermA and/or ermC. As deduced from the loss of either streptogramin A or
      streptogramin B resistance determinants in particular isolates, resistance to
      quinupristin-dalfopristin requires mechanisms conferring resistance to both
      compounds. The SmaI macrorestriction patterns of strains from hospitals in Lille
      and Lyon were different; however, similarity analysis suggested a relatedness of
      20 methicillin-resistant S. aureus strains from the Lille hospital, a finding
      confirmed by PCR typing based on three different genomic polymorphisms. These
      groups of isolates were found to be hetero-glycopeptide-intermediate susceptible
      S. aureus. Information about the failure of glycopeptide chemotherapy has not
      been available.

PMID- 11574578
TI  - Evaluation of two commercial enzyme immunoassays, testing immunoglobulin G (IgG)
      and IgA responses, for diagnosis of Helicobacter pylori infection in children.
AB  - Serological testing to diagnose Helicobacter pylori infection in children is
      still controversial, although commonly used in clinical practice. We compared the
      immunoglobulin G (IgG) and IgA results of two commercially available enzyme
      immunoassays (EIAs) (Pyloriset IgG and IgA and Enzygnost II IgG and IgA) for 175
      children with abdominal symptoms divided into three age groups (0 to < or =6
      years, n = 47; >6 to < or =12 years, n = 77; >12 years, n = 51). A child was
      considered H. pylori infected if at least two of three tests (histology, rapid
      urease test, 13C-urea breath test) or culture were positive and noninfected if
      all results were concordantly negative. Of 175 children, 93 (53%) were H. pylori
      negative and 82 were H. pylori positive. With the recommended cutoff values, the
      overall specificity was excellent for all four EIAs (95.7 to 97.8%) regardless of
      age. Sensitivity varied markedly between tests and was 92.7, 70.7, 47.5, and
      24.4% for Enzygnost II IgG, Pyloriset IgG, Enzygnost II IgA, and Pyloriset IgA,
      respectively. Sensitivity was low in the youngest age group (25 to 33.3%), except
      for Enzygnost II IgG (91.6%). Receiver-operating curve analyses revealed that
      lower cutoff values would improve the accuracy of all of the tests except
      Enzygnost II IgG. Measurement of specific IgA, in addition to IgG, antibodies
      hardly improved the sensitivity. The specificity of commercial serological tests
      is high in children when the cutoff values obtained from adults are used. In
      contrast, sensitivity is variable, with a strong age dependence in some, but not
      all, tests. We speculate that young children may have a different immune response
      to H. pylori, with preferable responses to certain antigens, as well as lower
      titers than adults. The Pyloriset test may fail to recognize these specific
      antibodies.

PMID- 11574579
TI  - Use of random amplified polymorphic DNA PCR to examine epidemiology of
      Stenotrophomonas maltophilia and Achromobacter (Alcaligenes) xylosoxidans from
      patients with cystic fibrosis.
AB  - Stenotrophomonas maltophilia and Achromobacter (Alcaligenes) xylosoxidans have
      been increasingly recognized as a cause of respiratory tract colonization in
      cystic fibrosis (CF). Although both organisms have been associated with
      progressive deterioration of pulmonary function, demonstration of causality is
      lacking. To examine the molecular epidemiology of S. maltophilia and A.
      xylosoxidans in CF, isolates from patients monitored for up to 2 years were
      fingerprinted using a PCR-based randomly amplified polymorphic DNA (RAPD-PCR)
      method. Sixty-one of 69 CF centers screened had 183 S. maltophilia culture
      positive patients, and 46 centers had 92 A. xylosoxidans-positive patients. At
      least one isolate from each patient was genotyped, and patients with > or =10
      positive cultures (12 S. maltophilia cultures, 15 A. xylosoxidans cultures) had
      serial isolates genotyped. In addition, centers with multiple culture-positive
      patients were examined for evidence of shared clones. There were no instances of
      shared genotypes among different CF centers. Some patients demonstrated isolates
      with a single genotype throughout the observation period, and others had
      intervening or sequential genotypes. At the six centers with multiple S.
      maltophilia culture-positive patients and the seven centers with multiple A.
      xylosoxidans-positive patients, there were three and five instances of shared
      genotypes, respectively. The majority of shared isolates were from pairs who were
      siblings or otherwise epidemiologically linked. These findings suggest RAPD-PCR
      typing can distinguish unique CF isolates of S. maltophilia and A. xylosoxidans,
      person-to-person transmission may occur, there are not a small number of clones
      infecting CF airways, and patients with long-term colonization may either have a
      persistent organism or may acquire additional organisms over time.

PMID- 11574580
TI  - Clinical evaluation of anti-tuberculous glycolipid immunoglobulin G antibody
      assay for rapid serodiagnosis of pulmonary tuberculosis.
AB  - Previously we reported the development of a highly sensitive enzyme-linked
      immunosorbent assay specific for anti-tuberculous glycolipid (anti-TBGL) for the
      rapid serodiagnosis of tuberculosis. In this study, the usefulness of an anti
      TBGL antibody assay kit for rapid serodiagnosis was evaluated in a controlled
      multicenter study. Antibody titers in sera from 318 patients with active
      pulmonary tuberculosis (216 positive for Mycobacterium tuberculosis in smear
      and/or culture tests and 102 smear and culture negative and clinically
      diagnosed), 58 patients with old tuberculosis, 177 patients with other
      respiratory diseases, 156 patients with nonrespiratory diseases, and 454 healthy
      subjects were examined. Sera from 256 younger healthy subjects from among the 454
      healthy subjects were examined as a control. When the cutoff point of anti-TBGL
      antibody titer was determined as 2.0 U/ml, the sensitivity for active
      tuberculosis patients was 81.1% and the specificity was 95.7%. Sensitivity in
      patients with smear-negative and culture-negative active pulmonary tuberculosis
      was 73.5%. Even in patients with noncavitary minimally advanced lesions, the
      positivity rate (60.0%) and the antibody titer (4.6 +/- 9.4 U/ml) were
      significantly higher than those in the healthy group. These results indicate that
      this assay using anti-TBGL antibody is useful for the rapid serodiagnosis of
      active pulmonary tuberculosis.

PMID- 11574581
TI  - Molecular typing of Salmonella serotypes prevalent in animals in England:
      assessment of methodology.
AB  - Salmonella enterica serotypes Derby, Mbandaka, Montevideo, Livingstone, and
      Senftenberg were among the 10 most prevalent serotypes isolated from farm animals
      in England and Wales in 1999. These serotypes are of potential zoonotic
      relevance; however, there is currently no "gold standard" fingerprinting method
      for them. A collection of isolates representing the former serotypes and serotype
      Gold Coast were analyzed using plasmid profiling, pulsed-field gel
      electrophoresis (PFGE), and ribotyping. The success of the molecular methods in
      identifying DNA polymorphisms was different for each serotype. Plasmid profiling
      was particularly useful for serotype Derby isolates, and it also provided a good
      level of discrimination for serotype Senftenberg. For most serotypes, we observed
      a number of nontypeable plasmid-free strains, which represents a limitation of
      this technique. Fingerprinting of genomic DNA by ribotyping and PFGE produced a
      significant variation in results, depending on the serotype of the strain. Both
      PstI/SphI ribotyping and XbaI-PFGE provided a similar degree of strain
      differentiation for serotype Derby and serotype Senftenberg, only marginally
      lower than that achieved by plasmid profiling. Ribotyping was less sensitive than
      PFGE when applied to serotype Mbandaka or serotype Montevideo. Serotype Gold
      Coast isolates were found to be nontypeable by XbaI-PFGE, and a significant
      proportion of them were found to be plasmid free. A similar situation applies to
      a number of serotype Livingstone isolates which were nontypeable by plasmid
      profiling and/or PFGE. In summary, the serotype of the isolates has a
      considerable influence in deciding the best typing strategy; a single method
      cannot be relied upon for discriminating between strains, and a combination of
      typing methods allows further discrimination.

PMID- 11574582
TI  - Multiplex PCR using internal transcribed spacer 1 and 2 regions for rapid
      detection and identification of yeast strains.
AB  - Multiplex PCR amplification followed by either agarose gel electrophoresis (PCR
      AGE) or microchip electrophoresis (PCR-ME) was used to test a total of 120 fungal
      strains. The internal transcribed spacer 1 (ITS1) and ITS2 regions and the 5.8S
      ribosomal DNA (rDNA) region of the fungi were amplified by using universal
      primers ITS1 and ITS4. The ITS2 region was simultaneously amplified by using
      universal primers ITS3 and ITS4. Since Trichosporon asahi and T. asteroides
      showed similar lengths for two amplicons, 29 different gel patterns were
      demonstrated for 30 yeast species tested on the basis of differences in the
      lengths of one or two amplicons. Of 75 yeast isolates from clinical materials, 5
      isolates (6.8%) which were incompletely identified or not identified by the
      phenotypic method were identified with our PCR-based method (2 isolates as
      Candida guilliermondii, 2 as C. krusei, and 1 as C. zeylanoides). No differences
      in discriminating power or sensitivity were observed between the PCR-AGE method
      and the PCR-ME method. These methods, prospectively applied to 24 yeast-positive
      blood culture bottles (16 patients), resulted in the correct detection of 24
      yeast strains. In conclusion, multiplex PCR followed by electrophoresis seems to
      be a promising tool for the rapid identification of common and uncommon yeast
      strains from culture colonies and from yeast-positive blood culture bottles (5.5
      h for the PCR-AGE method and 3 h for the PCR-ME method).

PMID- 11574583
TI  - Spoligotype diversity of Mycobacterium bovis strains isolated in France from 1979
      to 2000.
AB  - The molecular fingerprints of 1,349 isolates of Mycobacterium bovis received
      between 1979 and August 2000 at Agence Francaise de Securite Sanitaire des
      Aliments (Afssa) have been obtained by spoligotyping. The majority of the
      isolates (1,266) were obtained from cattle living in France. An apparently high
      level of heterogeneity was observed between isolates. One hundred sixty-one
      spoligotypes were observed in total, of which 153 were from French isolates. The
      two predominant spoligotypes, designated BCG-like and GB54, accounted for 26 and
      12% of the isolates, respectively. In addition, 84% of the spoligotypes were
      found fewer than 10 times. Analysis of the results by clustering and parsimony
      based algorithms revealed that the majority of the spoligotypes were closely
      related. The predominant spoligotype was identical to that of the vaccine strain
      Mycobacterium bovis BCG, which was isolated in France at the end of the 19th
      century. Some spoligotypes were closely associated with restricted geographical
      areas. Interestingly, some spoligotypes, which were frequently observed in
      France, were also observed in neighboring countries. Conversely, few spoligotypes
      were common to France and England, and those that were shared were observed at
      very different frequencies. This last point illustrates the potential role for an
      international data bank, which could help trace the spread of M. bovis across
      national borders.

PMID- 11574584
TI  - Comparison of the Vitek gram-positive susceptibility 106 card, the MRSA-Screen
      latex agglutination test, and mecA analysis for detecting oxacillin resistance in
      a geographically diverse collection of clinical isolates of coagulase-negative
      staphylococci.
AB  - The Vitek automated susceptibility testing system with a modified gram-positive
      susceptibility (GPS) 106 card (bioMerieux Vitek, Inc., Hazelwood. Mo.) and a
      rapid slide latex agglutination test (MRSA-Screen test; Denka Seiken Co., Ltd.,
      Tokyo, Japan) were evaluated for their abilities to detect oxacillin resistance
      in coagulase-negative staphylococci (CoNS). The reference broth microdilution
      method and the detection of the mecA gene by PCR ("gold standard" reference
      result) were used to compare the results obtained with the commercial products. A
      total of 123 clinical isolates consisting of eight species were selected from
      U.S. surveillance collections. Among the mecA-positive isolates (95 strains), 30
      isolates were initially negative on the MRSA-Screen test read at 3 min. When the
      agglutination reaction was extended for 10 min, 26 of the 30 isolates became
      positive. For a different four isolates, the oxacillin MIC was < or =0.25
      microg/ml on the Vitek GPS 106 card. Among the mecA-negative isolates (28
      strains), for two Staphylococcus warneri, two S. lugdunensis, and two S.
      saprophyticus strains MICs were > or =0.5 microg/ml by the reference broth
      microdilution method. Four of these isolates were also categorized as resistant
      with the Vitek GPS 106 card and two isolates were positive by the MRSA-Screen
      test. Overall, the MRSA-Screen test, GPS 106 card, and reference broth
      microdilution method had sensitivities of 95.7 (result at 10 min), 95.7, and
      100%, respectively, and specificities of 92.8, 85.7, and 78.5%, respectively.
      Although the MRSA-Screen test required a slight procedural modification, both
      commercial methods achieved a sensitivity and specificity at detecting oxacillin
      resistance in CoNS at a level that was acceptable for clinical laboratory use.

PMID- 11574585
TI  - Necessity of quality-controlled 16S rRNA gene sequence databases: identifying
      nontuberculous Mycobacterium species.
AB  - The use of the 16S rRNA gene for identification of nontuberculous mycobacteria
      (NTM) provides a faster and better ability to accurately identify them in
      addition to contributing significantly in the discovery of new species. Despite
      their associated problems, many rely on the use of public sequence databases for
      sequence comparisons. To best evaluate the taxonomic status of NTM species
      submitted to our reference laboratory, we have created a 16S rRNA sequence
      database by sequencing 121 American Type Culture Collection strains encompassing
      92 species of mycobacteria, and have also included chosen unique mycobacterial
      sequences from public sequence repositories. In addition, the Ribosomal
      Differentiation of Medical Microorganisms (RIDOM) service has made freely
      available on the Internet mycobacterial identification by 16S rRNA analysis. We
      have evaluated 122 clinical NTM species using our database, comparing >1,400 bp
      of the 16S gene, and the RIDOM database, comparing approximately 440 bp. The
      breakdown of analysis was as follows: 61 strains had a sequence with 100%
      similarity to the type strain of an established species, 19 strains showed a 1-
      to 5-bp divergence from an established species, 11 strains had sequences
      corresponding to uncharacterized strain sequences in public databases, and 31
      strains represented unique sequences. Our experience with analysis of the 16S
      rRNA gene of patient strains has shown that clear-cut results are not the rule.
      As many clinical, research, and environmental laboratories currently employ 16S
      based identification of bacteria, including mycobacteria, a freely available
      quality-controlled database such as that provided by RIDOM is essential to
      accurately identify species or detect true sequence variations leading to the
      discovery of new species.

PMID- 11574586
TI  - Detection of ciprofloxacin-resistant Yersinia pestis by fluorogenic PCR using the
      LightCycler.
AB  - We have developed a fluorescence resonance energy transfer (FRET)-based assay to
      detect ciprofloxacin resistant (Cp(r)) mutants of the biothreat agent Yersinia
      pestis. We selected spontaneous mutants of the attenuated Y. pestis KIM 5 strain
      that were resistant to a ciprofloxacin (CIP) concentration of at least 1
      microg/ml. DNA sequencing of gyrA encoded by 65 of these mutants revealed that
      all isolates contained one of four different point mutations within the quinolone
      resistance-determining region of gyrA. We developed a FRET-based assay that
      detected all of these mutations by using a single pair of fluorescent probes with
      sequences complementary to the wild-type Y. pestis gyrA sequence. Melting peak
      analysis revealed that the probe-PCR product hybrid was less stable when
      amplification occurred from any of the four mutant templates. This instability
      resulted in the PCR product obtained from the Cp(r) Y. pestis strains displaying
      a 4 to 11 degrees C shift in probe melting temperature. Following optimization of
      the reaction conditions, we were able to detect approximately 10 pg of purified
      wild-type template DNA or the presence of approximately 4 CFU of wild-type Y.
      pestis KIM 5 or Cp(r) mutants in crude lysates. Taken together, our results
      demonstrate the utility of FRET-based assays for detection of Cp(r) mutants of Y.
      pestis. This method is both sensitive and rapid.

PMID- 11574587
TI  - Quantitative detection of hepatitis B virus DNA by real-time nucleic acid
      sequence-based amplification with molecular beacon detection.
AB  - We have developed a hepatitis B virus (HBV) DNA detection and quantification
      system based on amplification with nucleic acid sequence-based amplification
      (NASBA) technology and real-time detection with molecular beacon technology.
      NASBA is normally applied to amplify single-stranded target RNA, producing RNA
      amplicons. In this work we show that with modifications like primer design,
      sample extraction method, and template denaturation, the NASBA technique can be
      made suitable for DNA target amplification resulting in RNA amplicons. A major
      advantage of our assay is the one-tube, isothermal nature of the method, which
      allows high-throughput applications for nucleic acid detection. The homogeneous
      real-time detection allows a closed-tube format of the assay, avoiding any
      postamplification handling of amplified material and therefore minimizing the
      risk of contamination of subsequent reactions. The assay has a detection range of
      10(3) to 10(9) HBV DNA copies/ml of plasma or serum (6 logs), with good
      reproducibility and precision. Compared with other HBV DNA assays, our assay
      provides good sensitivity, a wide dynamic range, and high-throughput
      applicability, making it a viable alternative to those based on other
      amplification or detection methods.

PMID- 11574588
TI  - Borrelia burgdorferi sensu lato and Ehrlichia spp. in Ixodes ticks from southern
      Norway.
AB  - We report the results of a study of the prevalence of Ehrlichia and Borrelia
      species in 341 questing Ixodes ricinus ticks from two locations in southern
      Norway. The prevalences of Borrelia burgdorferi sensu lato and Ehrlichia spp.
      were, respectively, 16 and 11.5% at site 1 and 17 and 6% at site 2. Prevalence
      and species composition of Borrelia and Ehrlichia varied with location and date
      of collection. The dominant Borrelia species at both sites was Borrelia afzelii,
      followed by Borrelia burgdorferi sensu stricto. Borrelia garinii was found in
      only a single tick. The dominant member of the Ehrlichia group was a recently
      described Ehrlichia-like organism related to the monocytic ehrlichiae. Variants
      of Ehrlichia phagocytophila and the agent of human granulocytic ehrlichiosis were
      also found. The highest prevalences for B. afzelii, B. burgdorferi sensu stricto,
      and the Ehrlichia-like organism were observed in May. B. afzelii was most
      prevalent in females, less prevalent in nymphs, and least prevalent in males,
      while the prevalence of Ehrlichia was highest in nymphs, lower in females, and
      least in males. Double infections with B. afzelii and B. burgdorferi sensu
      stricto and with B. afzelii and the Ehrlichia-like organism were significantly
      overrepresented. Tick densities were highest in May, when densities of more than
      200 ticks/100 m2 were observed, and declined during the summer months to
      densities as low as 20 ticks/100 m2. We conclude that estimates of the prevalence
      of tick-borne bacteria are sensitive to the choice of date and site for
      collection of ticks. This is the first study of tick-borne Borrelia and Ehrlichia
      in Norway and the lowest reported B. garinii prevalence in Northern Europe. The
      prevalence of the Ehrlichia-like organism is described for the first time in
      questing ticks.

PMID- 11574589
TI  - Flow cytometry compared with indirect immunofluorescence for rapid detection of
      dengue virus type 1 after amplification in tissue culture.
AB  - Dengue virus (DV) was detected early in infected mosquito C6/36 cells by using
      indirect immunofluorescence (IF) in conjunction with flow cytometry. Three
      fixation-permeabilization methods and three DV serotype 1 (DEN-1)-specific
      monoclonal antibodies, 8-8 (anti-E), 16-4 (anti-NS1), and 15F3-1 (anti-NS1), were
      evaluated for the detection of DEN-1 in infected C6/36 cells. We found that these
      three monoclonal antibodies were capable of detecting DV in C6/36 cells as early
      as 24 h postinoculation by using a conventional indirect IF stain. Both 8-8 and
      16-4 detected DV earlier and showed a greater number of DV-positive cells than
      15F3-1. In flow cytometry, 3% paraformaldehyde plus 0.1% Triton X-100 with 16-4,
      the best fixation-permeabilization method for testing DV, showed higher
      sensitivity (up to 1 PFU) than indirect IF stain. The higher sensitivity of 16-4
      in detecting DEN-1 was found with both IF and flow cytometry. Flow cytometry,
      which had a sensitivity similar to that of nested reverse transcription-PCR, was
      more sensitive in detecting DV in the infected mosquito cells 10 h earlier than
      the conventional IF stain. When clinical specimens were amplified in mosquito
      C6/36 cells and then assayed for DV using flow cytometry and conventional virus
      isolation at day 7 postinfection, both methods had 97.22% (35 out of 36)
      agreement. Moreover, among 12 positive samples which were detected by
      conventional culture method, the flow cytometry assay could detect DV in 58.33%
      (7 out of 12) of samples even at day 3 postinfection. In conclusion, both
      monoclonal antibodies 8-8 and 16-4 can be used for the early detection of DEN-1
      infected C6/36 cells, with 16-4 (anti-NS1) being the best choice for the rapid
      diagnosis of DV by both the IF staining and flow cytometry methods.

PMID- 11574590
TI  - Screening of active lyssavirus infection in wild bat populations by viral RNA
      detection on oropharyngeal swabs.
AB  - Brain analysis cannot be used for the investigation of active lyssavirus
      infection in healthy bats because most bat species are protected by conservation
      directives. Consequently, serology remains the only tool for performing
      virological studies on natural bat populations; however, the presence of
      antibodies merely reflects past exposure to the virus and is not a valid marker
      of active infection. This work describes a new nested reverse transcription (RT)
      PCR technique specifically designed for the detection of the European bat virus 1
      on oropharyngeal swabs obtained from bats but also able to amplify RNA from the
      remaining rabies-related lyssaviruses in brain samples. The technique was
      successfully used for surveillance of a serotine bat (Eptesicus serotinus) colony
      involved in a case of human exposure, in which 15 out of 71 oropharyngeal swabs
      were positive. Lyssavirus infection was detected on 13 oropharyngeal swabs but in
      only 5 brains out of the 34 animals from which simultaneous brain and
      oropharyngeal samples had been taken. The lyssavirus involved could be rapidly
      identified by automatic sequencing of the RT-PCR products obtained from 14 brains
      and three bat oropharyngeal swabs. In conclusion, RT-PCR using oropharyngeal
      swabs will permit screening of wild bat populations for active lyssavirus
      infection, for research or epidemiological purposes, in line not only with
      conservation policies but also in a more efficient manner than classical
      detection techniques used on the brain.

PMID- 11574591
TI  - Molecular identification of Campylobacter concisus.
AB  - A 1.6-kb DNA fragment isolated from a Campylobacter concisus genomic library gave
      C. concisus-specific restriction fragment length patterns when it was used as a
      probe in hybridization studies. All of the strains tested, including type strains
      and clinical isolates, contained a 0.5-kb HindIII fragment that hybridized to the
      probe. DNA sequencing of the 1.6-kb fragment identified three open reading frames
      (ORFs). One of the ORFs encodes the carboxy terminus of GyrB, and the
      translational products of ORF2 and ORF3 showed similarity to hypothetical
      proteins, previously identified in Campylobacter jejuni. DNA-DNA hybridization
      studies with a fragment internal to ORF3 showed that this sequence was
      responsible for the signal observed with the 0.5-kb HindIII fragment. A rapid PCR
      assay was developed and evaluated. Primers that annealed to the extremities of
      the 1.6-kb fragment were used to obtain an amplicon of the correct size from both
      reference and clinical strains of C. concisus.

PMID- 11574592
TI  - Serotype-specific detection of coxsackievirus A16 in clinical specimens by
      reverse transcription-nested PCR.
AB  - We describe the development of a coxsackievirus A16 (CVA16) serotype-specific PCR
      which correctly differentiated between CVA16 and other enterovirus serotypes of
      both laboratory isolates and clinical specimens. The assay will be useful for
      monitoring CVA16 outbreaks and studying the disease association, epidemiology,
      and evolution of this common enterovirus serotype.

PMID- 11574593
TI  - Identification of Staphylococcus spp. by PCR-restriction fragment length
      polymorphism of gap gene.
AB  - Oligonucleotide primers specific for the Staphylococcus aureus gap gene were
      previously designed to identify 12 Staphylococcus spp. by PCR. In the present
      study, AluI digestion of PCR-generated products rendered distinctive restriction
      fragment length polymorphism patterns that allowed 24 Staphylococcus spp. to be
      identified with high specificity.

PMID- 11574594
TI  - Evaluation of efficiency of screening extended-spectrum beta-lactamase-producing
      Escherichia coli and Klebsiella pneumoniae in hospitals where the bacteria are
      increasingly prevalent.
AB  - The disk screening methods for extended-spectrum beta-lactamase-producing strains
      were evaluated. The confirmatory work is reduced significantly in settings such
      as those in this study, by changing the cefpodoxime breakpoint to < or =20 mm and
      by not testing cefoxitin-resistant isolates. Cefotaxime and ceftazidime disk
      screening is reliable, and the laboratory-prepared cefotaxime- and ceftazidime
      clavulanic acid disks are stable at -20 degrees C for 12 weeks.

PMID- 11574595
TI  - Rapid detection of methicillin resistance in coagulase-negative staphylococci by
      a penicillin-binding protein 2a-specific latex agglutination test.
AB  - The detection of PBP 2a by the MRSA-Screen latex agglutination test with 201
      clinical coagulase-negative staphylococci had an initial sensitivity of 98% and a
      high degree of specificity for Staphylococcus epidermidis strains compared to PCR
      for mecA. Determination of oxacillin MICs evaluated according to the new
      breakpoint (0.5 microg/ml) of the National Committee for Clinical Laboratory
      Standards exhibited an extremely low specificity for this population.

PMID- 11574596
TI  - Contamination of transplantable human tumor-bearing lines by Helicobacter
      hepaticus and its elimination.
AB  - Helicobacter hepaticus contaminating nonfrozen tumors was transmissible to severe
      combined immunodeficient (SCID) mice, but the organism in cryopreserved samples
      was not. This suggests that H. hepaticus has the ability to spread via
      biomaterials and that freezing-thawing is able to reduce the numbers of organisms
      to levels insufficient for subcutaneous infection of SCID mice.

PMID- 11574597
TI  - Rapid differentiation of "Mycobacterium canettii" from other Mycobacterium
      tuberculosis complex organisms by PCR-restriction analysis of the hsp65 gene.
AB  - A total of 102 isolates of the Mycobacterium tuberculosis complex, including
      available "M. canettii" isolates, were studied by PCR-restriction analysis of a
      441-bp fragment of the hsp65 gene. PRA upon HhaI enzyme digestion (GCGC) allowed
      easy differentiation of "M. canettii" from other members of the M. tuberculosis
      complex (three bands of 260, 105, and 60 bp for "M. canetti," compared to four
      bands of 185, 105, 75, and 60 bp for other members of the M. tuberculosis
      complex). Sequencing of the 441-bp hsp65 fragment of "M. canettii" isolates
      showed the disappearance of an HhaI site at position 235 due to a C-to-T
      transition that corresponded to position 631 of the homologous hsp65 gene of M.
      tuberculosis H37Rv. Considering that "M. canettii" may also exist as a stable
      rough morphotype, we suggest that the true number of "M. canettii" isolates may
      be underestimated in clinical microbiology laboratories.

PMID- 11574598
TI  - Epidemiologic usefulness of spoligotyping for secondary typing of Mycobacterium
      tuberculosis isolates with low copy numbers of IS6110.
AB  - Restriction fragment length polymorphism (RFLP) analysis of IS6110 is commonly
      used to DNA fingerprint Mycobacterium tuberculosis. However, low-copy (< or =5)
      IS6110 M. tuberculosis strains are poorly differentiated, requiring secondary
      typing. When spoligotyping was used as the secondary method, only 13% of Maryland
      culture-positive tuberculosis (TB) patients with low-copy IS6110-spoligotyped
      clustered strains had epidemiologic linkages to another patient, compared to 48%
      of those with high-copy strains clustered by IS6110 alone (P < 0.01).
      Spoligotyping did not improve a population-based molecular epidemiologic study of
      recent TB transmission.

PMID- 11574600
TI  - Rapid detection of Mycobacterium tuberculosis in contaminated BACTEC 12B broth
      cultures by testing with Amplified Mycobacterium Tuberculosis Direct Test.
AB  - Contamination of broth cultures of acid-fast bacilli (AFB) by bacterial species
      other than Mycobacterium species frequently occurs. Many of these contaminated
      cultures require redecontamination and reincubation before the appropriate tests
      can be performed for identification, significantly affecting the turnaround time
      for reporting culture results. In this study, the Amplified Mycobacterium
      Tuberculosis Direct Test (MTD; Gen-Probe) was performed to detect the
      Mycobacterium tuberculosis complex (MTBC) in 125 BACTEC 12B broth cultures with
      positive growth indices. Among these, 41 grew non-AFB bacteria only, and all 41
      were negative by the MTD. The remaining 84 bottles contained contaminated
      cultures that grew both AFB and other bacteria or yeasts. Repeat decontamination
      and reincubation of these specimens required a mean time of 13 days (range, 3 to
      40 days). The MTD results were positive for 10 samples, 9 of which were MTBC
      culture positive and 1 of which grew Myobacterium celatum, a species known to
      cross-react in the MTD. All cultures growing other mycobacterial species were
      negative by the MTD. The results of this study demonstrate that the MTD is both
      sensitive and specific in detecting MTBC in contaminated broth cultures and that,
      when used selectively, the MTD can potentially rule in or out a diagnosis of MTBC
      as much as 12 days earlier than using nonamplified DNA probe testing alone can.

PMID- 11574599
TI  - PCR for specific detection of H7 flagellar variant of fliC among extraintestinal
      pathogenic Escherichia coli.
AB  - A newly developed PCR-based assay for the H7 variant of the Escherichia coli
      flagellin gene, fliC, was 100% sensitive and specific in comparison with serology
      and probe hybridization. It revealed broad conservation of the H7 fliC variant
      among phylogenetically diverse lineages of extraintestinal pathogenic E. coli
      (ExPEC) and superseded serotyping for certain isolates with ambiguous or non-H7
      serotyping results. The H7 primers functioned well when incorporated into a
      multiplex PCR assay for diverse virulence-associated genes of ExPEC.

PMID- 11574601
TI  - Ultrastructural study of Chlamydia pneumoniae in a continuous-infection model.
AB  - We have established an in vitro model of long-term continuous Chlamydia
      pneumoniae infection in HEp-2 cells. Using transmission electron microscopy, we
      demonstrated the presence of spontaneous abnormal chlamydial inclusions similar
      in appearance to the persistent chlamydial forms induced in vitro by treatment
      with cytokines or antibiotics or by nutrient deprivation.

PMID- 11574602
TI  - Increased prevalence of class I integrons in Escherichia coli, Klebsiella
      species, and Enterobacter species isolates over a 7-year period in a German
      university hospital.
AB  - The prevalence of integrons in five enterobacterial species was analyzed in 900
      blood culture isolates from 1993, 1996, and 1999. Remarkably, the prevalence
      increased from 4.7% in 1993 to 9.7% in 1996 and finally to 17.4% in 1999 (P <
      0.01). Within 7 years the combined percentage of P1 strong promoters and P1 weak
      plus P2 active promoters with high transcription efficacies has increased from
      23.1 to 33.3 and finally 60% (P < 0.05).

PMID- 11574603
TI  - Epidemiology and susceptibility of 3,051 Staphylococcus aureus isolates from 25
      university hospitals participating in the European SENTRY study.
AB  - A total of 3,051 methicillin-susceptible Staphylococcus aureus (MSSA) isolates
      and methicillin-resistant S. aureus (MRSA) isolates in Europe were compared. MRSA
      isolates constituted 25% of all isolates and were more prevalent in southern
      Europe. MRSA isolates appeared to be more prevalent in intensive care units than
      in outpatient departments. Only a small minority of MSSA isolates were multidrug
      resistant, whereas the majority of MRSA isolates were multidrug resistant.

PMID- 11574604
TI  - Evaluation of the Vitek card GPS105 and VTK-RO7.01 software for detection of
      oxacillin resistance in clinically relevant coagulase-negative staphylococci.
AB  - The performance of Vitek cards GPS105 with software version VTK-R07.01 for
      detection of oxacillin resistance in coagulase-negative staphylococci (CoNS) was
      compared to disk diffusion and PCR detection for mecA. The sensitivity and
      specificity of the Vitek GPS105 method were 97.6 and 85.5%, respectively.

PMID- 11574605
TI  - Molecular characterization of rifampin-resistant isolates of Mycobacterium
      tuberculosis from Hungary by DNA sequencing and the line probe assay.
AB  - Two regions of rpoB associated with rifampin resistance were sequenced in 29
      rifampin-resistant (determined by the proportion method) isolates of
      Mycobacterium tuberculosis obtained from patients from three counties in Hungary.
      Of the 29 resistant strains, 27 had a mutation in either the 81-bp region (26
      strains) or the N-terminal region (1 strain), while the other 2 strains had no
      mutations in either region. The locations and frequencies of the mutations
      differed from those previously reported. The most common mutation in this study,
      D516V, was found in 38% of the Hungarian strains, a frequency 2 to 10 times
      higher than that found in studies from other countries. These same 29 isolates
      were also evaluated with the Inno-LiPA Rif. TB test (LiPA), a reverse
      hybridization assay for the rapid detection of rifampin resistance. Although LiPA
      detected the presence of an rpoB mutation in 26 of the resistant isolates, the
      type of mutation could not be determined in 4 isolates because the mutations
      present were not among those included on the LiPA strip. In addition, a silent
      mutation in one of the rifampin-susceptible control strains was interpreted as
      rifampin resistant by LiPA. These findings demonstrate the importance of
      validating this rapid molecular test by comparison with DNA sequence results in
      each geographic location before incorporating the test into routine diagnostic
      work.

PMID- 11574606
TI  - Comparative performance of herpes simplex virus type 2-specific serologic assays
      from Meridian Diagnostics and MRL diagnostics.
AB  - MRL Diagnostics and Meridian Diagnostics have recently designed herpes simplex
      virus type 2 (HSV-2)-specific enzyme immunoassays for HSV-2 antibody detection.
      Blood donor sera were assayed for HSV-2 antibodies by both methods. The
      sensitivity, specificity, and efficiency were 97.9, 95.4, and 95.9% for the MRL
      assay and 83.2, 98.2, and 95.5% for the Meridian assay, respectively.

PMID- 11574607
TI  - Diagnostic yield of a PCR assay in focal complications of brucellosis.
AB  - In order to evaluate the diagnostic yield of a PCR assay for patients with focal
      complications of brucellosis, we studied by PCR and by conventional
      microbiological techniques 34 nonblood samples from 32 patients with different
      focal forms of brucellosis. The samples from patients with brucellosis were
      paired to an equal number of control samples from the same locations of patients
      whose illnesses had different etiologies. Thirty-three of the 34 nonblood samples
      (97%) from the brucellosis patients were positive by PCR, whereas Brucella spp.
      were isolated from only 29.4% of the conventional cultures. For 11.4% of the
      patients, the confirmatory serological tests were either negative or showed
      titers below the diagnostic range. Two patients (6.2%) from the control group,
      both with tuberculous vertebral osteomyelitis, had a positive PCR result. The
      brucella PCR of blood from these two patients was also positive, and the two
      strains of Mycobacterium tuberculosis isolated were analyzed by the brucella PCR,
      with no evidence of amplification. These results show that the PCR assay is far
      more sensitive than conventional cultures, and this, coupled with its speed and
      reduction in risk to laboratory workers, makes this technique a very useful tool
      for the diagnosis of focal complications of brucellosis.

PMID- 11574608
TI  - Identification of CTX-M-14 extended-spectrum beta-lactamase in clinical isolates
      of Shigella sonnei, Escherichia coli, and Klebsiella pneumoniae in Korea.
AB  - CTX-M-14 beta-lactamase was identified in a stool isolate of Shigella sonnei and
      in blood isolates of Escherichia coli (one isolate) and Klebsiella pneumoniae
      (two isolates) from different parts of Korea. The amino acid sequence differed by
      one amino acid from CTX-M-9 (Ala-231--> Val) and was identical to that of beta
      lactamases recently found in China and Japan.

PMID- 11574609
TI  - Removal of PCR inhibitors by silica membranes: evaluating the Amplicor
      Mycobacterium tuberculosis kit.
AB  - The effectiveness of PCR inhibitor removal by silica membranes in combination
      with the Amplicor Mycobacterium tuberculosis kit was analyzed for 655 respiratory
      and nonrespiratory specimens. The overall inhibition rate was reduced from 12.5%,
      when applying the Amplicor kit alone, to 1.1% with the addition of silica
      membrane DNA purification.

PMID- 11574610
TI  - Comparison and evaluation of antimicrobial susceptibility testing of enterococci
      performed in accordance with six national committee standardized disk diffusion
      procedures.
AB  - Studies were conducted to compare and evaluate antimicrobial susceptibility test
      results for enterococci obtained by six national committee disk diffusion
      procedures. Variations in the incidence of isolates in resistance categories and
      errors were associated with the use of ciprofloxacin, gentamicin, nitrofurantoin,
      rifampin, and teicoplanin in a number of committee procedures. Results indicate
      that laboratories performing disk diffusion antimicrobial susceptibility testing
      may have problems correctly identifying resistance in enterococci with agents
      used to combat infections and that it may be difficult to compare resistance data
      for surveillance purposes.

PMID- 11574611
TI  - Altering trends in the dominance of Shigella flexneri serotypes and emergence of
      serologically atypical S. flexneri strains in Dhaka, Bangladesh.
AB  - Of 469 recently isolated Shigella flexneri strains, 452 agglutinated with
      Shigella flexneri-specific monoclonal antibodies. Of these, 396 could be assigned
      to 10 of the currently recognized 15 serotypes, with S. flexneri 2b dominating
      (23.2%). Of the 56 untypeable strains which showed invasive properties, 17 were
      serologically atypical and the remaining 39 belonged to a new serotype.

PMID- 11574612
TI  - Longitudinal variability of human immunodeficiency virus type 1 RNA viral load
      measurements by nucleic acid sequence-based amplification and NucliSens assays in
      a large multicenter study.
AB  - Human immunodeficiency virus type 1 (HIV-1) RNA measurements were evaluated
      within an externally controlled multilaboratory program. Three external standards
      (1.5 x 10(3) to 1.5 x 10(6) copies/ml) were included in 814 assay runs by four
      laboratories. Results indicate that HIV-1 RNA levels can be measured with a
      precision equal to that of the pre-highly active antiretroviral therapy era
      (standard deviations, +/-0.16 to 0.25 log10 units).

PMID- 11574613
TI  - Evaluation of BACTEC MGIT 960 and BACTEC 460TB systems for recovery of
      mycobacteria from clinical specimens of a university hospital with low incidence
      of tuberculosis.
AB  - Clinical samples obtained over a period of 8 months (n = 2,624) were processed in
      parallel with the BACTEC 460TB system, with the MGIT 960 system, and in
      Lowenstein-Jensen (LJ) medium, resulting in the recovery of 127 mycobacteria.
      Recovery rates in combinations of the BACTEC 460TB or MGIT 960 system with LJ
      were, respectively, 94.7 and 94.7% for Mycobacterium tuberculosis complex (n =
      57) and 91.4 and 70.0% for nontuberculous mycobacteria (n = 70). Contamination
      rates, elevated in the MGIT 960 system, were associated with patients (cystic
      fibrosis) and type of material but not with transport time. Detection time was
      reduced in the MGIT 960 system.

PMID- 11574614
TI  - Simple and rational approach to the identification of Mycobacterium tuberculosis,
      Mycobacterium avium complex species, and other commonly isolated mycobacteria.
AB  - A novel PCR-restriction fragment length polymorphism analysis of the hsp65 gene
      was developed. The restriction patterns for Mycobacterium tuberculosis and
      Mycobacterium avium complex (MAC) species were designed to be highly distinct,
      and the overall number of restriction patterns was designed to be limited. Four
      hundred specimens (17 reference strains and 383 clinical isolates) were tested,
      of which 98 were M. tuberculosis and 132 were MAC species. The assay was
      virtually 100% sensitive and specific for M. tuberculosis and MAC species.
      Moreover, it gave highly concordant results for other mycobacterial species other
      than M. terrae complex species. This assay can be completed in one day and is
      user-friendly and robust. Therefore, it is highly suitable for large-scale use in
      a clinical laboratory.

PMID- 11574615
TI  - Contamination of the clinical microbiology laboratory with vancomycin-resistant
      enterococci and multidrug- resistant Enterobacteriaceae: implications for
      hospital and laboratory workers.
AB  - We surveyed environmental surfaces in our clinical microbiology laboratory to
      determine the prevalence of vancomycin-resistant enterococci (VRE) and multidrug
      resistant Enterobacteriaceae (MDRE) during a routine working day. From a total of
      193 surfaces, VRE were present on 20 (10%) and MDRE were present on 4 (2%) of the
      surfaces tested. In a subsequent survey after routine cleaning, all of the 24
      prior positive surfaces were found to be negative. Thus, those in the laboratory
      should recognize that many surfaces may be contaminated by resistant organisms
      during routine processing of patient specimens.

PMID- 11574616
TI  - Low concentrations of mupirocin in the pharynx following intranasal application
      may contribute to mupirocin resistance in methicillin-resistant Staphylococcus
      aureus.
AB  - We describe a patient with methicillin-resistant Staphylococcus aureus (MRSA)
      colonizing the pharynx. The MIC of mupirocin was 0.25 microg/ml before treatment
      and increased after treatment to 8 microg/ml. Using pulsed-field gel
      electrophoresis, we confirmed that the genotypes of MRSA that colonized the
      pharynx before and after the use of mupirocin were identical. We measured the
      delivery of mupirocin to the pharynx in three normal volunteers and two patients.
      Low concentrations of mupirocin were present in the pharynx in all cases 10 min
      to 3 days after intranasal application. Our data suggested that low
      concentrations of the drug in the pharynx after intranasal application of
      mupirocin ointment might explain the selection of mupirocin resistance in MRSA.

PMID- 11574617
TI  - Magnetic immuno-PCR assay with inhibitor removal for direct detection of
      Helicobacter pylori in human feces.
AB  - A PCR protocol was developed to detect Helicobacter pylori in human stool
      specimens. This protocol was based on the association of a magnetic immuno-PCR
      assay with a technique to remove inhibitors (agarose-embedded DNA preparation).
      Of the 47 H. pylori-positive and 57 H. pylori-negative patients included in this
      study, 38 were positive and 66 were negative by this new protocol. The
      sensitivity, specificity, and predictive values for a positive or a negative
      result were 80.9% (95% confidence interval [CI], 66.3 to 90.4), 100% (95% CI,
      92.1 to 100), 100% (95% CI, 88.6 to 100), and 86.4% (95% CI, 75.2 to 93.2),
      respectively.

PMID- 11574618
TI  - Optimal inoculation methods and quality control for the NCCLS oxacillin agar
      screen test for detection of oxacillin resistance in Staphylococcus aureus.
AB  - To define more precisely the inoculation methods to be used in the oxacillin
      screen test for Staphylococcus aureus, we tested agar screen plates prepared in
      house with 6 microg of oxacillin/ml and 4% NaCl using the four different
      inoculation methods that would most likely be used by clinical laboratories. The
      organisms selected for testing were 19 heteroresistant mecA-producing strains and
      41 non-mecA-producing strains for which oxacillin MICs were near the susceptible
      breakpoint. The inoculation method that was preferred by all four readers and
      that resulted in the best combination of sensitivity and specificity was a 1
      microl loopful of a 0.5 McFarland suspension. A second objective of the study was
      to then use this method to inoculate plates from five different manufacturers of
      commercially prepared media. Although all commercial media performed with
      acceptable sensitivity compared to the reference lot, one of the commercial lots
      demonstrated a lack of specificity. Those lots of oxacillin screen medium that
      fail to grow heteroresistant strains can be detected by using S. aureus ATCC
      43300 as a positive control in the test and by using transmitted light to
      carefully examine the plates for any growth. However, lack of specificity with
      commercial lots may be difficult to detect using any of the current quality
      control organisms.

PMID- 11574619
TI  - Performance of eight methods, including two new rapid methods, for detection of
      oxacillin resistance in a challenge set of Staphylococcus aureus organisms.
AB  - Using a set of 55 Staphylococcus aureus challenge organisms, we evaluated six
      routine methods (broth microdilution, disk diffusion, oxacillin agar screen,
      MicroScan conventional panels, MicroScan rapid panels, and Vitek cards) currently
      used in many clinical laboratories and two new rapid methods, Velogene and the
      MRSA-Screen, that require less than a day to determine the susceptibility of S.
      aureus to oxacillin. The methods were evaluated by using the presence of the mecA
      gene, as detected by PCR, as the "gold standard." The strains included 19 mecA
      positive heterogeneously resistant strains of expression class 1 or 2
      (demonstrating oxacillin MICs of 4 to >16 microg/ml) and 36 mecA-negative
      strains. The oxacillin MICs of the latter strains were 0.25 to 4 microg/ml when
      tested by broth microdilution with 2% NaCl-supplemented cation-adjusted Mueller
      Hinton broth as specified by the NCCLS. However, when tested by agar dilution
      with 4% salt (the conditions used in the oxacillin agar screen method), the
      oxacillin MICs of 16 of the mecA-negative strains increased to 4 to 8 microg/ml.
      On initial testing, the percentages of correct results (% sensitivity/%
      specificity) were as follows: broth microdilution, 100/100; Velogene, 100/100;
      Vitek, 95/97; oxacillin agar screen, 90/92; disk diffusion, 100/89; MicroScan
      rapid panels, 90/86; MRSA-Screen, 90/100; and MicroScan conventional, 74/97. The
      MRSA-Screen sensitivity improved to 100% if agglutination reactions were read at
      15 min. Repeat testing improved the performance of some but not all of the
      systems.

PMID- 11574620
TI  - Heterogeneity and compartmentalization of Pneumocystis carinii f. sp. hominis
      genotypes in autopsy lungs.
AB  - The extent and importance of genotype heterogeneity of Pneumocystis carinii f.
      sp. hominis within lungs have not previously been investigated. Two hundred forty
      PCR clones obtained from respiratory specimens and lung segments from three
      patients with fatal P. carinii pneumonia were investigated to detect genetic
      diversity in the internal transcribed spacer (ITS) region of the nuclear rRNA
      operon, the mitochondrial large-subunit (mtLSU) rRNA gene, and the
      dihydropteroate synthase-encoding gene. For two of the three examined patients, a
      mixture of different mtLSU rRNA and ITS genotypes was observed. Not all genotypes
      present in the lungs at autopsy were detected in the diagnostic respiratory
      samples. Compartmentalization of specific ITS and mtLSU rRNA sequence types was
      observed in different lung segments. In conclusion, the interpretation of
      genotype data and in particular ITS sequence types in the assessment of
      epidemiological questions should be cautious since genotyping done on respiratory
      samples cannot a priori be assumed to represent all genotypes present within the
      lung.

PMID- 11574621
TI  - Performance of candida ID, a new chromogenic medium for presumptive
      identification of Candida species, in comparison to CHROMagar Candida.
AB  - Candida ID agar allows identification of Candida albicans and differentiation of
      other Candida species. In comparison with CHROMagar Candida, we evaluated the
      performance of this medium directly from 596 clinical specimens. In particular,
      detection of C. albicans after 24 h of incubation was easier on Candida ID
      (sensitivity, 96.8%) than on CHROMagar (sensitivity, 49.6%).

PMID- 11574622
TI  - Amino acid substitution within the VP7 protein of G2 rotavirus strains associated
      with failure to serotype.
AB  - Rotavirus strains collected in the United Kingdom during the 1995-1996 season and
      genotyped as G2 by reverse transcription-PCR failed to serotype in enzyme-linked
      immunosorbent assays using three different G2-specific monoclonal antibodies. The
      deduced amino acid sequences of the antigenic regions A (amino acids 87 to 101),
      B (amino acids 142 to 152), and C (amino acids 208 to 221) of VP7 revealed that a
      substitution at position 96 (Asp-->Asn) correlated with the change in ability to
      serotype these G2 strains.

PMID- 11574623
TI  - Evaluation of BacT/Alert 3D liquid culture system for recovery of mycobacteria
      from clinical specimens using sodium dodecyl (lauryl) sulfate-NaOH
      decontamination.
AB  - A total of 52 mycobacterial isolates were recovered from 1,197 clinical specimens
      decontaminated by a sodium dodecyl (lauryl) sulfate (SDS)-NaOH protocol. Of
      these, 94% were recovered with the BacT/Alert 3D system (Organon Teknika, Durham,
      N.C.) and 79% were recovered on Lowenstein-Jensen (LJ) medium. Mean times to
      detection of organisms of the Mycobacterium tuberculosis complex (n = 47) were
      22.8 days with LJ medium and 16.2 days with the system. The BacT/Alert 3D system
      is a rapid and efficient detection system which can be used with an SDS-NaOH
      decontamination procedure.

PMID- 11574624
TI  - Value of throat swab in diagnosis of melioidosis.
AB  - Throat swab (TS) cultures were performed for 1,011 patients with melioidosis and
      3,524 healthy subjects or patients with other diseases. The specificity of TS
      culture for the diagnosis of melioidosis was 100%, and the overall sensitivity
      was 36% (24% for sputum-negative patients and 79% for sputum-positive patients).
      Direct plating of the TS specimen on Ashdown's medium was rapid (colonies were
      usually evident within 24 h) but only 63% sensitive compared to the results of
      primary culture in a selective broth. A throat swab should be cultured in all
      cases of suspected melioidosis.

PMID- 11574625
TI  - V3 serological subtyping of human immunodeficiency virus type 2 infection is not
      relevant.
AB  - V3 enzyme immunoassays have been shown to discriminate effectively between human
      immunodeficiency virus type 1 (HIV-1) subtypes. The aim of this study was to
      investigate the feasibility of V3 serotyping for HIV-2 infection. We serotyped 29
      sera with three peptides, corresponding to the V3 loop of subtypes A, B, and D of
      HIV-2. Sera were collected from HIV-2-infected patients, whose infecting strains
      were sequenced and subjected to phylogenetic analysis. Our results indicate that
      HIV-2 serotyping using V3 peptides is not relevant. V3 serotyping data were not
      consistent with genotyping results. The V3-A and V3-D peptides displayed poor
      discrimination, and the V3-B peptide was not representative of circulating
      viruses. Comparison of amino acid sequences and serotype reactivities
      demonstrated the importance of positions 309 and 314, located on either side of
      the tip of the V3 loop, in antibody binding.

PMID- 11574626
TI  - Cancer chemoprevention as adjuvant therapy for hepatocellular carcinoma.

PMID- 11574627
TI  - Apoptosis induction by acyclic retinoid: a molecular basis of 'clonal deletion'
      therapy for hepatocellular carcinoma.
AB  - We have shown previously that administration of acyclic retinoid to cirrhotic
      patients who had undergone curative treatment of preceding hepatocellular
      carcinoma (HCC) induced the disappearance of serum lectin-reactive alpha
      fetoprotein (AFP-L3) and subsequently reduced the incidence of second liver
      cancers. AFP-L3 is a tumor marker that indicates the presence of occult tumors
      below the detection limit by diagnostic images. Therefore, we have proposed a new
      concept of 'clonal deletion' therapy with acyclic retinoid for the cancer
      chemoprevention against HCC. Such eradication of AFP-L3-producing latent
      malignant (or premalignant) cells from the liver suggested a new strategy to
      prevent HCC, which may be involved in the same category as cancer chemotherapy.
      In the present series of studies, we explored the molecular mechanism of 'clonal
      deletion' and found a novel mechanism of apoptosis induction by the retinoid. We
      have demonstrated a modification of a retinoid receptor, RXRalpha, by mitogen
      activated protein (MAP) kinase-dependent phosphorylation, resulting in the loss
      of transactivating activity. This may lead HCC cells to be resistant to natural
      retinoic acid. However, acyclic retinoid restored the function of phosphorylated
      RXRalpha and induced its downstream pro-apoptotic genes including tissue
      transglutaminase, an enzyme that is implicated in apoptosis. Tissue
      transglutaminase-dependent apoptosis in HCC cells was independent of the
      activation of caspases. This novel mechanism of retinoid-induced apoptosis may
      give a clue to understand the molecular mechanism of clonal deletion.

PMID- 11574628
TI  - Retrospective comparison of the AJCC 5th edition classification for
      nasopharyngeal carcinoma with the AJCC 4th edition: an experience in Taiwan.
AB  - OBJECTIVE: The aim of this study was to compare the new AJCC 5th edition
      classification system for nasopharyngeal carcinoma (NPC) with the AJCC 4th
      edition by re-evaluating the staging of patients treated in Taiwan. METHODS: From
      1992 through 1996, 117 NPC patients without distant metastasis were treated using
      complete courses of radiotherapy. All patients had complete CT examinations of
      the nasopharynx and neck. Each patient was re-staged according to the 5th edition
      of the AJCC classification system. Their overall survival (OS), loco-regional
      relapse-free survival (LRRFS), distant metastasis-free survival (DMFS) and
      disease-free survival (DFS) were compared between the two staging systems, using
      the Kaplan-Meier method, log-rank test, Wilcoxon test and Cox proportional hazard
      model. RESULTS: After a median follow-up of 58.3 months, the 5-year OS for stage
      I, II, III and IV was 88, 86, 61 and 48%, respectively, according to the new
      staging. A more even distribution of patients was noted among the patients
      classified according to the AJCC 5th edition than the 4th edition. The
      distribution of stages I, II, III and IV was 13.7, 37.6, 15.4 and 33.3%,
      respectively, using the new staging system, whereas it was 0.8, 14.5, 20.5 and
      64.2%, respectively, using the old staging system. More statistically significant
      differences among 5th edition stages and T classifications than the 4th edition
      were also noted. CONCLUSIONS: The 5th edition of the AJCC staging system appears
      to have a more even distribution of patients and more statistically significant
      differences in predicting prognosis than the 4th edition, mostly in stages and T
      classification.

PMID- 11574629
TI  - Clinical effect of irinotecan in advanced and metastatic breast cancer patients
      previously treated with doxorubicin- and docetaxel-containing regimens.
AB  - BACKGROUND: Previous phase II trials in Japan suggested that irinotecan was a
      promising agent for advanced or metastatic breast cancer pretreated with
      anthracycline. However, irinotecan has not yet been evaluated in the salvage
      setting for breast cancer pretreated with both anthracycline and taxane, which
      are two active agents for breast cancer. METHODS: The efficacy and safety of
      irinotecan were retrospectively evaluated in patients with breast cancer who had
      previously been treated with both doxorubicin and docetaxel. From 1996 to 1999,
      irinotecan was administered to 20 patients, all with a performance status of <2.
      Irinotecan treatment was repeated in approximately 6 week cycles consisting of
      the administration of irinotecan once weekly for 4 weeks followed by a 2 week
      rest. The median dose of irinotecan administered was 100 mg/m(2) weekly. The
      median number of irinotecan cycles given was 1 (range: 1-8 cycles). The median
      total dose was 388 mg/m(2) (range: 50-2400 mg/m(2)). RESULTS: Performance status
      declined to >3 after treatment with irinotecan in four patients. Two patients had
      grade 3 leukopenia; three had grade 3 anemia and one had a creatinine elevation
      of grade 4. The objective response rate for all patients was 5.0% (95% CI: 0
      15.5%). The median time to progression and overall survival were 35 days (range:
      17-285 days) and 124 days (range: 17-667 days), respectively, since the start of
      the administration of irinotecan. CONCLUSIONS: Salvage chemotherapy with
      irinotecan may be inactive against advanced and metastatic breast cancer
      pretreated with doxorubicin and docetaxel. We will evaluate irinotecan for
      advanced and metastatic breast cancer patients as first- or second-line
      chemotherapy combined with anthracycline or taxane.

PMID- 11574630
TI  - Concurrent chemoradiotherapy for squamous cell carcinoma of thoracic esophagus:
      feasibility and outcome of large regional field and high-dose external beam boost
      irradiation.
AB  - OBJECTIVE: To assess the feasibility and outcome of concurrent chemoradiotherapy
      (CT-RT) with large regional field and high-dose external beam boost irradiation
      in thoracic esophageal cancer. METHODS: Patients with clinical stage T1
      (submucosal)-4N0-1M0 (UICC 1997) squamous cell carcinoma of the thoracic
      esophagus were eligible. Radiotherapy consisted of regional irradiation
      (extending from supraclavicular fossa to the paracardial area) with 39.6 Gy
      followed by high-dose external beam boost up to 66.6 Gy (1.8 Gy/day, five times
      per week). Two-hour infusion of cisplatin (80 mg/m(2) on day 1) and continuous
      infusion of 5-fluorouracil (800 mg/m(2)/day on days 2-6) were administered
      concurrently with radiotherapy, every 3-4 weeks, for two cycles. RESULTS: Thirty
      patients (stage I, 3; stage II, 11; stage III, 16) were entered into the study.
      Twenty-one patients (70%) completed the planned treatment. In elderly (> or = 70
      years) patients, four of six withdrew. Grade 3 and 4 toxicities (NCI-CTC) were
      observed in 20 (67%) and three (10%) patients, respectively. Major toxicities
      were blood, gastrointestinal (i.e. nausea and esophagitis) and pulmonary. There
      was no grade 5 (fatal) toxicity. The median follow-up period for surviving
      patients was 27 months (range: 9-49 months). The median survival time was 21
      months. The 1- and 2-year survival rates were 65 and 49% for all 30 patients. The
      incidence of esophageal stricture (grade 1-2: RTOG) was 21%. No patient suffered
      fistula formation. CONCLUSIONS: Despite poor compliance for elderly patients and
      frequent severe toxicities, our concurrent CT-RT resulted in a favorable outcome
      in thoracic esophageal cancer.

PMID- 11574631
TI  - Retrospective study of hyponatremia in gastric cancer patients treated with a
      combination chemotherapy of 5-fluorouracil and cisplatin: a possible warning sign
      of severe hematological toxicities?
AB  - BACKGROUND: Some anti-neoplastic agents induce hyponatremia. The relationship
      between hyponatremia and other toxicities in gastric cancer patients treated with
      5-fluorouracil and cisplatin (FP) was investigated retrospectively to clarify its
      clinical significance. METHODS: The subjects were 50 advanced gastric cancer
      patients treated with FP. Patients' performance status, oral intake,
      nausea/vomiting, diarrhea, fever, urine volume, presence of ascites or pleural
      effusion, laboratory data and administration of diuretics, corticosteroid and
      contents and volume of hydration before and during the first 5 days after
      chemotherapy were reviewed. RESULTS: The serum sodium level decreased after
      initiation of chemotherapy in all patients and the lowest level (nadir) was most
      frequently observed on day 8 (range, days 2-14), which preceded hematological
      toxicities. In 10 patients (20%) the nadir of serum sodium was lower than 125
      mEq/l. We classified these 10 patients as a low-sodium group and the others into
      a normal-sodium group. Six (60%) and seven (70%) of the 10 patients in the low
      sodium group had complications with grade 3 or 4 leukopenia and thrombocytopenia,
      whereas only one (3%) and two (5%) were seen in the normal-sodium group (p <
      0.0001). Stomatitis and diarrhea were also slightly more severe in the former
      than the latter group. With respect to sensitivity and probability, receiver
      operating characteristic curves showed the nadir ((> or = ) or <125 mEq/l) of the
      serum sodium level was the best marker for both leukopenia and thrombocytopenia.
      CONCLUSION: Hyponatremia after initiation of chemotherapy with FP may be a
      warning sign of subsequent severe hematological toxicity.

PMID- 11574632
TI  - High preoperative plasma D-dimer level is associated with advanced tumor stage
      and short survival after curative resection in patients with colorectal cancer.
AB  - BACKGROUND: An elevated plasma D-dimer level indicates activation of coagulation
      and fibrinolysis. Previous studies demonstrated that the preoperative plasma D
      dimer level correlates with tumor stage in patients with colorectal cancer. This
      study examined the relationship between preoperative plasma D-dimer level and
      both pathological findings and TNM classification and examined the prognostic
      significance of preoperative plasma D-dimer level. METHODS: Preoperative plasma D
      dimer levels were measured in 93 patients who underwent curative resection of
      colorectal cancer and 40 patients with benign colorectal diseases other than
      inflammatory bowel disease. The results were analyzed for correlations between
      preoperative plasma D-dimer levels in patients with colorectal cancer and
      pathological findings, TNM classification and postoperative survival. RESULTS:
      Preoperative plasma D-dimer levels were significantly higher in patients with
      colorectal cancer than in patients with benign colorectal diseases. Plasma D
      dimer levels were higher in patients with tumors that were relatively large, had
      relatively deep wall penetration and were at a relatively advanced TNM stage.
      Higher preoperative plasma D-dimer levels were significantly associated with
      shorter postoperative overall survival. Results of analysis with a multivariate
      proportional hazard model suggested that preoperative plasma D-dimer level was
      the third strongest prognostic factor; exceeded in importance only by lymph node
      status and preoperative carcinoembryonic antigen level. CONCLUSIONS: Elevated
      plasma D-dimer levels in patients with colorectal cancer are associated with
      relatively advanced tumor stage and short postoperative survival after curative
      resection. It appears that measurement of preoperative D-dimer level would be
      useful in the preoperative diagnosis of tumor stage and prediction of
      postoperative survival.

PMID- 11574633
TI  - Weekly 1 hour paclitaxel infusion in patients with recurrent gynecological
      tumors: a pilot study.
AB  - BACKGROUND: Intensifying the dose of paclitaxel given in a weekly schedule is
      useful towards improving the therapeutic index of paclitaxel in treating a
      variety of advanced and recurrent malignancies and is suitable for outpatient
      administration. This pilot study was carried out to evaluate the safety of weekly
      paclitaxel administration by 1 h infusion in the outpatient setting. METHODS:
      Eleven patients with recurrent gynecological tumors who had previously been
      treated with at least one platinum-based chemotherapy regimen participated in the
      study between May 1999 and March 2000. Paclitaxel was given at a dose of 70
      mg/m(2 ) as a 1 h infusion every week for at least 20 consecutive weeks unless
      lesions became progressive. Intravenous dexamethasone and cimetidine and oral
      diphenhydramine were administered 30 min before paclitaxel infusion. RESULTS: The
      11 patients received a total of 166 cycles of therapy. All patients received 70
      mg/m(2 ) doses of paclitaxel without treatment delay. No hypersensitivity
      reactions were elicited. Grade 3 or 4 leukopenia and neutropenia occurred in 9
      and 36% of the patients, respectively. Granulocyte colony-stimulating factor was
      required for only one patient and no patients experienced febrile neutropenia.
      Neurotoxicity was the most serious adverse effect and all patients experienced
      grade 1 or 2 peripheral neuropathy. Grade 1 or 2 myalgias were observed in 45% of
      the patients. Alopecia was universal. No Grade 3 or higher non-hematological
      toxicities were observed. CONCLUSION: Weekly 1 h paclitaxel administration is
      considered safe as a salvage therapy for recurrent gynecological tumors, making
      its use more convenient and easier in the outpatient setting. The current results
      support further evaluation.

PMID- 11574634
TI  - Prognostic variables in patients who have undergone radical cystectomy for
      transitional cell carcinoma of the bladder.
AB  - OBJECTIVE: To evaluate whether several clinicopathological factors could be used
      as prognostic predictors in patients who have undergone radical cystectomy for
      transitional cell carcinoma (TCC) of the bladder. METHODS: Between January 1985
      and June 2000, 154 patients underwent radical cystectomy and pelvic
      lymphadenectomy for TCC of the bladder at a single institution. Their
      clinicopathological findings were analyzed based on the criteria of the Japanese
      Urological Association. RESULTS: Histopathological examination revealed that the
      tumor grade was 1 or 2 in 22 patients and 3 in 132 patients; the pathological
      stage was pT1 or less in 30 patients, pT2 in 51 patients, pT3 in 53 patients and
      pT4 in 20 patients. Vascular involvement and lymph node metastasis were found in
      85 and 33 patients, respectively. The cause-specific 5-year survival rate was
      64.2% for all patients, 74.4% for patients with grade 1 or 2 tumors, 62.9% for
      those with grade 3 tumors; 90.9% for those with stage pT1 or less, 77.9% for
      those with stage pT2, 45.0% for those with stage pT3 and 29.2% for those with
      stage pT4 (p < 0.001); 83.2% for patients without vascular involvement and 42.0%
      for those with vascular invasion (p < 0.001); and 76.5% for patients without
      lymph node metastasis and 22.7% for those with lymph node metastasis (p < 0.001).
      Multivariate analysis revealed a strong independent correlation of the
      pathological stage and lymph node metastasis with poor prognosis and,
      furthermore, the incidence of lymph node metastasis was significantly related to
      the increase in pathological stage. CONCLUSIONS: In this series, the pathological
      stage, lymph node metastasis and vascular involvement, but not tumor grade, were
      significantly useful prognostic factors in patients who have undergone radical
      cystectomy for TCC and among them only pathological stage and lymph node
      metastasis could be used as independent predictors for poor prognosis.

PMID- 11574635
TI  - Dendritic cells activate antitumor immunity for malignant intracranial germ cell
      tumor: a case report.
AB  - We report a 22-year-old male patient with a history of intracranial malignant
      germ cell tumor (GCT) who had undergone tumor resection twice, followed by
      radiation and chemotherapy. The tumor had rapidly recurred along the entire
      ventricular wall with extensive invasion into the brain parenchyma. The serum
      level of human beta-chorionic gonadotropin (beta-hCG) was 232.3 ng/ml on
      admission. Although tissue samples of the recurrent tumor could not be obtained,
      the previous histological diagnosis of germinoma and elevated serum beta-hCG
      levels suggested recurrence of malignant GCT. The patient declined chemotherapy
      but accepted dendritic cell (DC)-based immunotherapy. DC inoculation five times
      resulted in rapid tumor shrinkage and a significant decrease in the serum level
      of beta-hCG. Here we discuss the effectiveness of immunotherapy using DCs for
      recurrent intracranial malignant GCTs.

PMID- 11574636
TI  - A case of bone metastasis from gastric carcinoma after a nine-year disease-free
      interval.
AB  - A case featuring very late and unusual metastasis of gastric cancer is presented.
      A 49-year-old woman presented with metastatic disease in the seventh cervical
      vertebra 9 years after a total gastrectomy for gastric carcinoma. The resected
      primary tumor was a Borrman type III, poorly differentiated adenocarcinoma which
      had invaded the subserosal layer of the stomach and had generated lymph node
      metastases. The patient was treated for the metastatic tumor with sequential
      administration of cisplatin, calcium leucovorin and 5-fluorouracil and subsequent
      irradiation. Remission was achieved and she survived for a further 13 months
      without major symptoms.

PMID- 11574637
TI  - Cancer incidence and incidence rates in Japan in 1996: estimates based on data
      from 10 population-based cancer registries.

PMID- 11574640
TI  - Surgically induced Charcot's foot.
AB  - The neuropathic foot has the potential to develop Charcot arthropathy. This study
      describes multiple cases of Charcot's foot following surgery. Of all the cases
      described, only one patient had any preexisting Charcot deformity or acute
      Charcot event. The study concludes that alterations of mechanical forces in the
      foot play an important role in triggering an acute Charcot episode.

PMID- 11574641
TI  - Flake-Austin modification of the STA-Peg arthroereisis: a retrospective study.
AB  - The Smith subtalar arthroereisis implant (STA-peg) is used to correct severe
      collapsing pes valgoplanus in children. Flake and Austin modified the placement
      of this implant to block the leading wall of the lateral talus. Twenty-one
      patients with a total of 40 STA-peg procedures were evaluated subjectively and
      objectively. The average age at the time of surgery was 9.7 years (4 to 16
      years). The follow-up period averaged 36 months (12 to 90 months). The
      subjective, objective, and radiographic results were positive and the
      complication rate was low. A significant advantage of the Flake-Austin
      modification of the STA-peg placement in transverse planar dominant foot types is
      also noted.

PMID- 11574642
TI  - Hemophilic arthropathy: considerations in management.
AB  - The authors evaluate nonsurgical and surgical approaches to treating patients
      with hemophilic arthropathy and review the functional and economic limitations
      imposed on treating these patients. Indications for surgery are discussed and a
      case study that incorporates both conservative and surgical management options is
      presented. While the advent of factor replacement therapy has dramatically
      changed the course of treatment and prognosis for patients with hemophilia, the
      authors argue that the economic burden of treating these patients is still very
      high. The authors recommend that proper conservative and surgical management
      options for patients with hemophilia should be based upon a thorough
      understanding of the disease process.

PMID- 11574643
TI  - Talar fractures: three case studies.
AB  - Three case studies of fractures are presented that demonstrate the potential
      morbidity that these injuries can cause as well as the acceptable outcomes if
      treated appropriately. Two of the cases are talar fracture dislocations; the
      third is an osteochondral fracture of the talus. The importance of early
      treatment with open reduction and internal fixation is demonstrated. Success
      following surgical intervention in a nonhealed osteochondral fracture of the
      talus is also demonstrated.

PMID- 11574645
TI  - Arthrodesis of the interphalangeal joint of the hallux: a simple and effective
      technique.
AB  - The authors present a simple and effective technique to achieve arthrodesis of
      the hallucal interphalangeal joint. Stabilization is achieved by external
      fixation with crossing Kirschner wires joined together to create a single
      functional unit, a technique that avoids common problems often associated with
      Kirschner-wire fixation. The authors propose that this simple technique be
      considered for patients in whom it has been determined that screw fixation should
      not be used to obtain fusion of the interphalangeal joint.

PMID- 11574644
TI  - Posterior facet talocalcaneal coalition.
AB  - Posterior facet talocalcaneal coalition is one of the rarest forms of
      talocalcaneal coalition. When a posterior facet coalition occurs, it typically
      involves a majority of the posterior facet articular surface. The authors present
      a rare form of posterior facet talocalcaneal coalition in an 11- year-old girl. A
      brief review of the literature is provided, along with the case history,
      including radiographic findings and intraoperative and postoperative
      illustrations.

PMID- 11574646
TI  - Commentary: ensuring adequate reporting of randomized, controlled trials: the
      CONSORT statement.

PMID- 11574648
TI  - The CONSORT statement: revised recommendations for improving the quality of
      reports of parallel-group randomized trials.
AB  - To comprehend the results of a randomized, controlled trial (RCT), readers must
      understand its design, conduct, analysis, and interpretation. That goal can be
      achieved only through complete transparency from authors. Despite several decades
      of educational efforts, the reporting of RCTs needs improvement. Investigators
      and editors developed the original CONSORT (Consolidated Standards of Reporting
      Trials) statement to help authors improve reporting by using a checklist and flow
      diagram. The revised CONSORT statement presented in this paper incorporates new
      evidence and addresses some criticisms of the original statement. The checklist
      items pertain to the content of the Title, Abstract, Introduction, Methods,
      Results, and Discussion. The revised checklist includes 22 items selected because
      empirical evidence indicates that not reporting the information is associated
      with biased estimates of treatment effect or because the information is essential
      to judge the reliability or relevance of the findings. We intended the flow
      diagram to depict the passage of participants through an RCT. The revised flow
      diagram depicts information from four stages of trial (enrollment, intervention
      allocation, follow-up, and analysis). The diagram explicitly includes the number
      of participants, for each intervention group, that are included in the primary
      data analysis. Inclusion of these numbers allows the reader to judge whether the
      authors have performed an intention-to-treat analysis. In sum, the CONSORT
      statement is intended to improve the reporting of an RCT, enabling readers to
      understand a trial's conduct and to assess the validity of its results.

PMID- 11574649
TI  - Fighting to level the playing field with managed care.

PMID- 11574650
TI  - The new ethics of abortion.

PMID- 11574651
TI  - Is there a 'new ethics of abortion'?
AB  - This paper argues that the central issue in the abortion debate has not changed
      since 1967 when the English parliament enacted the Abortion Act. That central
      issue concerns the moral status of the human fetus. The debate here is not, it is
      argued, primarily a moral debate, but rather a metaphysical debate and/or a
      theological debate--though one with massive moral implications. It concerns the
      nature and attributes that an entity requires to have "full moral standing" or
      "moral inviolability" including a "right to life". It concerns the question when,
      in its development from newly fertilised ovum to unequivocally mature, autonomous
      morally inviolable person does a human being acquire that nature and those
      attributes, and thus a "right to life". The paper briefly reviews standard
      answers to these questions, outlining some problems associated with each. Finally
      there is a brief discussion of one way in which the abortion debate has changed
      since 1967--notably in the increasingly vociferous claim, especially from
      disability rights sectors, that abortion on grounds of fetal abnormality implies
      contempt for and rejection of disabled people--a claim that is rebutted.

PMID- 11574652
TI  - Reproductive autonomy and the ethics of abortion.
AB  - Abortion is one of the most controversial issues in today's world. People tend to
      turn to the law when trying to decide what is the best possible solution to an
      unwanted pregnancy. Here the author's views on abortion are discussed from a
      lawyer's and a woman's point of view. By taking into consideration the rights of
      the fetus an "antagonistic relationship" between the woman and her unborn child
      may occur. Therefore, women should have more autonomy in the issue. The article
      concludes with examples of cases in the United States and Ireland where the
      rights of the fetus are considered more important than those of the mother
      because of existing laws. This article suggests that a more inclusive ethics of
      abortion is required rather than a new ethics of abortion when "translating fetal
      life into law".

PMID- 11574653
TI  - Medical paternalism and the fetus.
AB  - A number of developments in the medical field have changed the debate about the
      ethics of abortion. These developments include: advances in fetal physiology, the
      increase in neonatal intensive care and the survival rates of premature infants.
      This paper discusses the idea of selective termination and the effects that these
      decisions have on disabled people of today. It presents a critique of the
      counselling services that are provided for the parents of a disabled fetus and
      discusses how this is viewed from a social perspective. The article ends with an
      argument that the mother deserves to be autonomous in the decision of abortion.
      The easiest and most fair way to develop her autonomy is to consider the
      relationship between a professional and a mother as an expert-expert
      relationship. Here both parties are considered experts in diagnostic information,
      treatment options, possibilities, and their history, family roots, philosophy and
      way of life, respectively.

PMID- 11574654
TI  - Screening for disability: a eugenic pursuit?
AB  - This article is written in response to the idea that selective termination may be
      eugenic. It points out that a mixture of motives and goals may inform screening
      programmes and selective termination for fetal abnormality without the intention
      being "eugenic". The paper locates modern genetics within the tradition of
      humanist medicine by suggesting that parents who choose to terminate a pregnancy
      because of fetal abnormalities are not making moral judgments about those who are
      living with these abnormalities already. Rather they are making judgments about
      their own lives and the lives of their children in relation to this genetic
      disorder. It concludes by introducing several caveats about the counselling that
      parents receive after the results of the testing and suggests that counselling
      inevitably contains a directive element because of the nature of the information
      covered.

PMID- 11574655
TI  - The place for individual conscience.
AB  - From a liberationist, feminist, and Catholic point of view, this article attempts
      to understand the decision of abortion. People are constantly testing their
      principles and values against the question of abortion. Advances in technology,
      the rise of communitarianism and the rejection of individualism, and the
      commodification of children are factors in the way in which the abortion debate
      is being constructed in society. The paper offers solutions to end the ugliness
      of the abortion debate by suggesting that we would be able to progress further on
      the issue of abortion if we looked for the good in the opposing viewpoint. The
      article continues with a discussion of Catholics For a Free Choice's position on
      abortion, and notes firstly that there is no firm position within the Catholic
      Church on when the fetus becomes a person; secondly that the principle of
      probablism in Roman Catholicism holds that where the church cannot speak
      definitively on a matter of fact (in this case, on the personhood of the fetus),
      the consciences of individual Catholics must be primary and respected, and
      thirdly that the absolute prohibition on abortion by the church is not
      infallible. In conclusion, only the woman herself can make the abortion decision.

PMID- 11574656
TI  - Issues for service providers: a response to points raised.
AB  - The issue of abortion has evolved since 1967. In this paper, the shift in the
      discourses of abortion are discussed. The article suggests that abortion is used
      as a "back-up" method of family planning and that this is broadly acceptable.
      Although there is little public opposition to abortion as such, there are
      influences that undermine abortion provision as it now exists. Growing concern
      about the status of the fetus shapes a number of debates. For example the issue
      of what the fetus feels during abortion influences abortion practice. Advances in
      technology and the increase in knowledge about the unborn fetus will not change a
      woman's decision about having a late termination. The article concludes with the
      idea that a woman is a moral, civilised human being that deserves the right to
      make decisions about her reproductive life.

PMID- 11574657
TI  - About abortion in Britain.

PMID- 11574658
TI  - About BPAS. The British Pregnancy Advisory Service.

PMID- 11574659
TI  - Sperm nuclear matrix association of the PRM1-->PRM2-->TNP2 domain is independent
      of Alu methylation.
AB  - Genes or multigenic chromosomal regions are organized by the nuclear matrix into
      a series of functionally discrete genic domains. Biophysical analysis of the
      human chromosome 16p13.13 region has shown that the PRM1-->PRM2-->TNP2 protamine
      containing multigenic locus is bounded by two sperm nuclear matrix attachment
      regions (MAR). This domain exists in a transcriptionally readied or potentiated
      (i.e. open) chromatin state when associated with the nuclear matrix. The MAR
      bounded PRM1-->PRM2-->TNP2 locus is nestled in an Alu repetitive element dense
      region. Fluorescence in-situ hybridization, analysis of sperm nuclear matrix/halo
      preparations showed that the PRM1-->PRM2-->TNP2 domain specifically localizes to
      the sperm nuclear matrix. This raised the question of whether nuclear matrix
      association and gene expression in this locus is mediated by Alu methylation. The
      methylation status of the various Alu elements contained within the human PRM1-
      >PRM2-->TNP2 locus was therefore assayed. The seven Alu elements tested,
      including those associated with the matrix attachment regions within the PRM1-
      >PRM2-->TNP2 locus, were fully methylated in sperm DNA. Conversely, these same
      Alu repeats were hypomethylated within the erythroleukaemic cell line, K562,
      which does not express any of the genes from this domain. This study shows that
      Alu methylation status is independent of attachment of PRM1-->PRM2-->TNP2 locus
      to the nuclear matrix and that Alu methylation does not play a leading role in
      the regulation of this domain.

PMID- 11574660
TI  - Tyrosine nitration in human spermatozoa: a physiological function of
      peroxynitrite, the reaction product of nitric oxide and superoxide.
AB  - Tyrosine nitration is a widely used marker of peroxynitrite (ONOO-) produced from
      the reaction of nitric oxide (NO.) with superoxide (O2(.-)). Since human
      spermatozoa are able to produce both NO. and O2(.-) during capacitation in vitro,
      we investigated whether spontaneous tyrosine nitration of proteins occurs in
      human spermatozoa and evaluated the physiological effects of peroxynitrite on
      sperm function. We report here that human spermatozoa, incubated for 8 h under
      conditions conducive to capacitation, display a reproducible pattern of protein
      tyrosine nitration. Several proteins with mol. wt of 105-14 kDa become
      increasingly tyrosine-nitrated after 15 min incubation and then minimal changes
      are observed. Treatment of capacitated spermatozoa with human follicular fluid or
      calcium ionophore causes an increase of the nitrotyrosine content of proteins at
      the mol. wt of 85 kDa. Moreover, exposure of spermatozoa to ONOO- (2.5-50
      micromol/l) increases motility and primes spermatozoa to respond earlier to human
      follicular fluid. ONOO- also increases protein tyrosine nitration and
      phosphorylation in a concentration-dependent manner. Taken together, these
      results demonstrate that tyrosine nitration of sperm proteins occurs in
      capacitated human spermatozoa, and that low concentrations of ONOO- modulate
      sperm functions, emphasizing the concept that capacitation is part of an
      oxidative process.

PMID- 11574661
TI  - Co-localization of the inositol 1,4,5-trisphosphate receptor and calreticulin in
      the equatorial segment and in membrane bounded vesicles in the cytoplasmic
      droplet of human spermatozoa.
AB  - Modulation of the intracellular calcium concentration within mammalian
      spermatozoa is important in several pre-fertilization events including
      hyperactivated motility and the acrosome reaction. To identify calcium binding
      proteins (CBP) potentially regulating these processes, a (45)Ca overlay technique
      was employed on 2-D blots of human sperm extracts. Microsequencing by Edman
      degradation and CAD mass spectrometry identified a relatively abundant 60.5 kDa
      CBP with a pI of 4.2 as calreticulin (CRT). Immunofluorescent labelling with anti
      CRT antibodies localized CRT to the acrosome, with highest fluorescence in the
      equatorial segment, and in the cytoplasmic droplets of 94 and 48% of human
      spermatozoa respectively. Double immunolabelling experiments demonstrated co
      localization of CRT and the inositol 1,4,5-trisphosphate receptor (IP(3)R) in the
      acrosome, in the equatorial segment, and vesicular structures in the cytoplasmic
      droplets of the neck region. Electron microscopic immunogold labelling localized
      CRT to the equatorial segment of acrosome-reacted spermatozoa and to membrane
      enclosed vesicles within the cytoplasmic droplet of both acrosome-intact and
      acrosome-reacted spermatozoa. Localization of the IP(3) receptor to the CRT
      containing vesicles, in the sperm neck and to the acrosome, suggests that
      capacitative calcium entry in human spermatozoa may be regulated from these
      putative calcium storage sites.

PMID- 11574663
TI  - Characterization of telomerase activity in the human oocyte and preimplantation
      embryo.
AB  - Telomerase, a ribonucleoprotein, has been described as an essential component of
      highly proliferative cells as it stabilizes the telomeres and avoids cellular
      senescence. The objective of this study was to modify the polymerase chain
      reaction-based telomeric repeat amplification protocol to detect telomerase
      activity in the single cell and to characterize the activity expressed in the
      human oocyte through to the blastocyst stage embryo. A comparative evaluation of
      telomerase activity and developmental stage was conducted using discarded or
      donated human oocytes and embryos. Telomerase activity was detected in all
      developmental stages evaluated from immature oocytes through to blastocyst stage
      embryos. Immature oocytes and blastocysts had similar levels of telomerase
      activity; however, both groups had significantly (P < 0.05) higher activity than
      zygote through to pre-morula stage embryos. Seventy-five thawed zygotes were
      cultured to day 3, biopsied by removing 1-2 cells, and the biopsied embryos were
      cultured to blastocyst stage. There was no difference (P < 0.05) in telomerase
      activity between cells biopsied from embryos that reached the blastocyst stage
      and cells from those that arrested in growth. This study has shown that human
      oocytes through to blastocyst stage embryos express telomerase activity, but that
      the level of telomerase activity in biopsied blastomeres, of the day 3 cleavage
      stage embryo, is not predictive of embryonic growth potential.

PMID- 11574662
TI  - Epididymal epithelium immortalized by simian virus 40 large T antigen: a model to
      study epididymal gene expression.
AB  - Primary cultures of the differentiated, adult epididymal duct epithelium were
      immortalized by retroviral transduction with the simian virus (SV)40 large T
      antigen. The canine epididymis was chosen here as a model with high human
      relevance, representing a convenient and acceptable source of differentiated
      epididymal tissue and, compared to other animal models, expressing a relatively
      large number of gene products which are also expressed by the human epididymis.
      To determine whether the immortalized canine epididymal (IMCE) cells retained a
      phenotype comparable to the original tissue, epithelial cytokeratins, various
      epididymal transcription factors as well as mRNAs encoding abundant epididymal
      secretory proteins, were studied as molecular markers. All IMCE populations
      obtained after transduction were of epithelial origin. The nuclear androgen
      receptor (AR) and the polyoma enhancer activator (PEA3), as well as the
      epididymal mRNA encoding the canine counterparts of human HE1, HE4 and HE5/CD52
      epididymal mRNA, were retained in all populations tested. The majority of tested
      clones were oestrogen receptor ERalpha-positive, but ERbeta-negative, while one
      ERalpha-negative cell population was positive for ERbeta. The IMCE populations
      described thus represent useful permanent tools for studying gene expression of
      the epididymal duct epithelium, and for other types of experiments, examples
      including drug effects and toxicity on the epididymis.

PMID- 11574664
TI  - The effect of cAMP on ion transport in Fallopian tube epithelial cells in vitro.
AB  - The coupled movement of ions and water across epithelia determines the
      composition and volume of fluid present in the lumen of organs. The second
      messenger cAMP is important in effecting electrolyte and water transport in many
      transporting epithelia; however, its role in Fallopian tube transport is
      uncertain. We have conducted electrophysiological studies on Fallopian tube
      epithelial cell monolayers in Ussing chambers and have demonstrated that
      exogenously added cAMP and agents that generate its intracellular production
      results in an increase in short-circuit current consistent with the transport of
      net electrical charge from a basal to mucosal direction. In contrast to the known
      effects of ATP in this tissue, the increase in short-circuit current was not
      explicable in terms of electrogenic chloride secretion as it was not affected by
      the chloride channel inhibitors, 4-acetamido-4'-isothiocyanostilbene-2,2
      disulphonic acid 1 mmol/l (SITS) and frusemide. Instead the current was reduced
      by the sodium channel inhibitor, amiloride, and was therefore, in part,
      explicable in terms of electrogenic Na+ absorption. These findings will enhance
      our understanding of the physiological mechanisms responsible for human Fallopian
      tubal fluid formation and composition.

PMID- 11574665
TI  - Characterization of relaxin binding in the uterus of the marmoset monkey.
AB  - The ovarian peptide hormone relaxin (RLX) plays an important role in the
      regulation of the endometrium both during the cycle and in early pregnancy. RLX
      interacts with specific receptors on endometrial stromal cells causing these to
      decidualize. In order to characterize the molecules with which RLX interacts in
      the primate uterus, a methodology based on a fully bioactive preparation of
      biotinylated porcine RLX was applied to cryosections of the uterus of female
      marmoset monkeys. Specific RLX binding was weakly detected in the proliferative
      phase in isolated endometrial stromal cells. In the secretory phase, the
      positively reacting cells increased in staining intensity and in number and also
      included some epithelial cells. Further increases occurred in pregnancy, but RLX
      binding in the endometrium decreased at the end of the cycle if pregnancy did not
      occur. The myometrium showed weak staining which did not vary through the cycle,
      but increased in pregnancy. Electrophoretic analysis of the RLX-binding moieties
      in these tissue sections indicated that a protein of approximately 40 kDa was the
      principal RLX-binding molecule, while minor specific bands were detectable at
      approximately 100 and approximately 200 kDa. The binding of biotinylated RLX
      could be specifically suppressed by co-incubation with unlabelled RLX, but not by
      insulin, IGF-I or biotin. This technique therefore allows the detection and
      molecular characterization of specific RLX binding in the primate uterus. In the
      marmoset monkey, the pattern of specific binding closely reflects the RLX
      dependent physiology during implantation and early pregnancy, implying the
      probable involvement of a specific RLX receptor.

PMID- 11574666
TI  - Interleukin-10 is produced by human uterine natural killer cells but does not
      affect their production of interferon-gamma.
AB  - A predominance of T helper (Th)2-type cytokines and a weakening of Th1 responses
      seem to be critical for the maintenance of a successful gestation. Among Th2-type
      cytokines, interleukin (IL)-10 is produced by human cytotrophoblasts and defects
      in this production result in specific pathological conditions of pregnancy. The
      current opinion is that IL-10 serves to protect the fetus from a harmful maternal
      immune response. However, production of the cytokine and its direct effect on
      uterine natural killer (uNK) cells, which represent the predominant lymphocyte
      population infiltrating the pregnant endometrium, are largely unknown. Thus, to
      shed light on the cytokine network at the maternal-fetal barrier during early
      pregnancy, we investigated the IL-10 system in uNK cells. We showed that uNK
      cells express the mRNA transcripts for IL-10 and IL-10 receptor. Production of IL
      10 by the uNK cells was enhanced by both IL-2 and IL-12. Treatment with IL-10
      alone enhanced uNK cell cytotoxic activity. In contrast, the cytokine did not
      modify the basal or stimulated production of interferon (IFN)-gamma by uNK. Thus,
      IL-10 does not act as a direct antagonist of uNK cell function and activation.
      However, IL-10 produced by uNK cells in response to IL-12 and IL-2 may still have
      a feedback inhibitory effect on the production of deleterious cytokines within
      the uterine microenvironment.

PMID- 11574667
TI  - Nitric oxide increases matrix metalloproteinase-1 production in human uterine
      cervical fibroblast cells.
AB  - Since uterine cervical ripening is an active biochemical process similar in part
      to an inflammatory reaction, nitric oxide (NO) has been proposed as a key
      mediator of this event. However, the mechanism by which NO modulates human
      cervical ripening has not been fully elucidated. In the present study we
      investigated the presence of NO synthases in human uterine cervix by
      immunohistochemistry and reverse transcriptase-polymerase chain reaction
      analysis. Furthermore, we examined the presence of NO-mediated regulation of
      matrix metalloproteinase-1 (MMP-1) production in cultured human uterine cervical
      fibroblast cells using enzyme-linked immunosorbent assay and Northern blot
      analysis. Endothelial and inducible NO synthases were detected in the form of
      mRNA and protein expression in pregnant uterine cervix. Interleukin-1alpha (IL
      1alpha) increased the expression of inducible NO synthase mRNA in cultured human
      uterine cervical fibroblast cells. IL-1alpha also increased MMP-1 secretion from
      the cultured cervical fibroblast cells. This IL-1alpha-augmented MMP-1 secretion
      was partially but significantly blocked by an NO synthase inhibitor, N(G)-nitro-L
      arginine methyl ester. On the other hand, NO donors increased MMP-1 production in
      the cultured cervical fibroblast cells. These findings together suggest that NO
      contributes to the process of cervical ripening via enhancement of MMP-1
      production, and that IL-1alpha increases MMP-1 secretion from cervical
      fibroblasts at least in part via NO synthesis.

PMID- 11574668
TI  - High deletion frequency of the complete AZFa sequence in men with Sertoli-cell
      only syndrome.
AB  - We have developed a rapid screening protocol for deletion analysis of the
      complete AZFa sequence (i.e. 792 kb) on the Y chromosome of patients with
      idiopathic Sertoli-cell-only (SCO) syndrome. This Y deletion was mapped earlier
      in proximal Yq11 and first found in the Y chromosome of the SCO patient JOLAR,
      now designated as the AZFa reference patient. We now show that similar AZFa
      deletions occur with a frequency of 9% in the SCO patient group. In two multiplex
      polymerase chain reaction experiments, deletions of the complete AZFa sequence
      were identified by a typical deletion pattern of four new sequence-tagged sites
      (STS): AZFa-prox1, positive; AZFa-prox2, negative; AZFa-dist1, negative; AZFa
      dist2, positive. The STS were established in the proximal and distal
      neighbourhoods of the two retroviral sequence blocks (HERV15yq1 and HERV15yq2)
      which encompass the break-point sites for AZFa deletions of the human Y
      chromosome. We have found deletions of the complete AZFa sequence always
      associated with a uniform SCO pattern on testicular biopsies. Patients with other
      testicular histologies as described in the literature and in this paper have only
      partial AZFa deletions. The current AZFa screening protocols can therefore be
      improved by analysing the extension of AZFa deletions. This may provide a
      valuable prognostic tool for infertility clinics performing testicular sperm
      extraction, as it would enable the exclusion of AZFa patients with a complete SCO
      syndrome.

PMID- 11574669
TI  - Six unaffected livebirths following preimplantation diagnosis for spinal muscular
      atrophy.
AB  - Spinal muscular atrophy (SMA) is a severe neurodegenerative autosomal recessive
      disorder, second only in frequency to cystic fibrosis. In its most severe form,
      SMA type I (Werdnig-Hoffman), death invariably ensues before age 2 years from
      respiratory failure or infection. Around 98% of clinical cases of SMA are caused
      by the homozygous absence of a region of exons 7 and 8 of the telomeric copy of
      the SMN gene (SMN1) on chromosome 5. We have developed a novel means of
      preimplantation diagnosis of SMA using a nested polymerase chain reaction (PCR)
      amplification of exon 7 of SMN, followed by a HinfI restriction digest of the PCR
      product enabling the important SMN1 gene to be distinguished from the centromeric
      SMN2 gene which has no clinical phenotype. This method was designed to reduce the
      likelihood of misdiagnosis. Five couples were treated using this method. Four
      proceeded to embryo transfer which resulted in six liveborns (one singleton, one
      twin and one triplet), all free of SMA. Embryo transfer was not performed in one
      cycle because of PCR contamination.

PMID- 11574670
TI  - Clinical application of multiplex quantitative fluorescent polymerase chain
      reaction (QF-PCR) for the rapid prenatal detection of common chromosome
      aneuploidies.
AB  - The clinical application of quantitative fluorescent polymerase chain reaction
      (QF-PCR) for rapid prenatal detection of chromosome aneuploidies has been limited
      in most studies to the detection of autosomal trisomies. Recently it has been
      shown that a newly identified highly polymorphic marker, termed X22, which maps
      to the Xq/Yq pseudoautosomal region of the sex chromosomes, used together with
      the X-linked short tandem repeat (STR) HPRT, allows the accurate detection of
      gonosome aneuploidies. We have developed a rapid assay, which includes these STR
      markers together with a sequence of the amelogenin region of the sex chromosomes
      and selected highly polymorphic autosomal STR. Two more X chromosome markers, as
      yet not used in previous QF-PCR applications, were also included in the assay.
      The molecular test was then used in a clinical trial on 551 uncultured amniotic
      fluid samples, allowing the assessment of copy number for chromosomes X, Y and 21
      in 100% of cases. In the course of this study, two fetuses with Turner's syndrome
      and one with Klinefelter's syndrome were identified along with 17 autosomal
      trisomies. The assay proved to be so efficient and reliable that in most
      aneuploidy cases, in which ultrasound findings were in agreement with the
      molecular result, therapeutical interventions were possible without waiting for
      the result of cytogenetic analysis.

PMID- 11574671
TI  - Identification of functionally relevant histidine residues in the apoptotic
      nuclease CAD.
AB  - The caspase-activated DNase CAD (DFF40/CPAN) degrades chromosomal DNA during
      apoptosis. Chemical modification with DEPC inactivates the enzyme, suggesting
      that histidine residues play a decisive role in the catalytic mechanism of this
      nuclease. Sequence alignment of murine CAD with four homologous apoptotic
      nucleases reveals four completely (His242, His263, His304 and His308) and two
      partially (His127 and His313) conserved histidine residues in the catalytic
      domain of the enzyme. We have changed these residues to asparagine and
      characterised the variant enzymes with respect to their DNA cleavage activity,
      structural integrity and oligomeric state. All variants show a decrease in
      activity compared to the wild-type nuclease as measured by a plasmid DNA cleavage
      assay. H242N, H263N and H313N exhibit DNA cleavage activities below 5% and H308N
      displays a drastically altered DNA cleavage pattern compared to wild-type CAD.
      Whereas all variants but one have the same secondary structure composition and
      oligomeric state, H242N does not, suggesting that His242 has an important
      structural role. On the basis of these results, possible roles for His127,
      His263, His304, His308 and His313 in DNA binding and cleavage are discussed for
      murine CAD.

PMID- 11574672
TI  - Modelling ion binding to AA platform motifs in RNA: a continuum solvent study
      including conformational adaptation.
AB  - Binding of monovalent and divalent cations to two adenine-adenine platform
      structures from the Tetrahymena group I intron ribozyme has been studied using
      continuum solvent models based on the generalised Born and the finite-difference
      Poisson-Boltzmann approaches. The adenine-adenine platform RNA motif forms an
      experimentally characterised monovalent ion binding site important for ribozyme
      folding and function. Qualitative agreement between calculated and experimental
      ion placements and binding selectivity was obtained. The inclusion of solvation
      effects turned out to be important to obtain low energy structures and ion
      binding placements in agreement with the experiment. The calculations indicate
      that differences in solvation of the isolated ions contribute to the calculated
      ion binding preference. However, Coulomb attraction and van der Waals
      interactions due to ion size differences and RNA conformational adaptation also
      influence the calculated ion binding affinity. The calculated alkali ion binding
      selectivity for both platforms followed the order K(+) > Na(+) > Rb(+) > Cs(+) >
      Li(+) (Eisenman series VI) in the case of allowing RNA conformational relaxation
      during docking. With rigid RNA an Eisenman series V was obtained (K(+) > Rb(+) >
      Na(+) > Cs(+) > Li(+)). Systematic energy minimisation docking simulations
      starting from several hundred initial placements of potassium ions on the surface
      of platform containing RNA fragments identified a coordination geometry in
      agreement with the experiment as the lowest energy binding site. The approach
      could be helpful to identify putative ion binding sites in nucleic acid
      structures determined at low resolution or with experimental methods that do not
      allow identification of ion binding sites.

PMID- 11574673
TI  - Characterisation of PAUSE-1, a powerful silencer in the human plasminogen
      activator inhibitor type 2 gene promoter.
AB  - Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor
      traditionally regarded as a regulator of fibrinolysis and extracellular matrix
      degradation. More recently, PAI-2 has been implicated in diverse processes such
      as keratinocyte differentiation, cell death and viral pathogenesis. The PAI-2
      promoter tightly regulates PAI-2 gene expression in a cell-specific manner and
      this control is mediated, in part, by the upstream silencer element, PAUSE-1.
      Here we have defined PAUSE-1 and investigated its activity as a silencer. A
      series of mutations were generated within the PAUSE-1 element and analysed for
      transcription factor binding and transcriptional silencing activity. These
      studies have defined the minimal functional PAUSE-1 element as
      TCTN(x)AGAN(3)T(4), where x = 0, 2 or 4. Examination of related elements present
      in other promoters, such as the human IFNbeta promoter, suggests that PAUSE-1 is
      a member of a family of universal silencers with the consensus sequence
      TCTN(x)AGA. UV crosslinking analyses determined that the PAUSE-1 binding protein
      was approximately 67 kDa. Insertion of PAUSE-1 into the heterologous (SV40) or
      the minimal PAI-2 promoters silenced transcription by 2.5-fold. These data show
      that PAUSE-1 acts as a powerful silencer of PAI-2 gene transcription and is
      likely to be important in the silencing of other genes as well.

PMID- 11574674
TI  - A computational approach to identify genes for functional RNAs in genomic
      sequences.
AB  - Currently there is no successful computational approach for identification of
      genes encoding novel functional RNAs (fRNAs) in genomic sequences. We have
      developed a machine learning approach using neural networks and support vector
      machines to extract common features among known RNAs for prediction of new RNA
      genes in the unannotated regions of prokaryotic and archaeal genomes. The
      Escherichia coli genome was used for development, but we have applied this method
      to several other bacterial and archaeal genomes. Networks based on nucleotide
      composition were 80-90% accurate in jackknife testing experiments for bacteria
      and 90-99% for hyperthermophilic archaea. We also achieved a significant
      improvement in accuracy by combining these predictions with those obtained using
      a second set of parameters consisting of known RNA sequence motifs and the
      calculated free energy of folding. Several known fRNAs not included in the
      training datasets were identified as well as several hundred predicted novel
      RNAs. These studies indicate that there are many unidentified RNAs in simple
      genomes that can be predicted computationally as a precursor to experimental
      study. Public access to our RNA gene predictions and an interface for user
      predictions is available via the web.

PMID- 11574675
TI  - PNRC2 is a 16 kDa coactivator that interacts with nuclear receptors through an
      SH3-binding motif.
AB  - PNRC2 (proline-rich nuclear receptor co-regulatory protein 2) was identified
      using mouse steroidogenic factor 1 (SF1) as bait in a yeast two-hybrid screening
      of a human mammary gland cDNA expression library. PNRC2 is an unusual coactivator
      in that it is the smallest coactivator identified so far, with a molecular weight
      of 16 kDa, and interacts with nuclear receptors using a proline-rich sequence. In
      yeast two-hybrid assays PNRC2 interacted with orphan receptors SF1 and estrogen
      receptor-related receptor alpha1 in a ligand-independent manner. PNRC2 was also
      found to interact with the ligand-binding domains of estrogen receptor,
      glucocorticoid receptor, progesterone receptor, thyroid receptor, retinoic acid
      receptor and retinoid X receptor in a ligand-dependent manner. A functional
      activation function 2 domain is required for nuclear receptors to interact with
      PNRC2. Using the yeast two-hybrid assay, the region amino acids 85-139 was found
      to be responsible for the interaction with nuclear receptors. This region
      contains an SH3 domain-binding motif (SEPPSPS) and an NR box-like sequence
      (LKTLL). A mutagenesis study has shown that the SH3 domain-binding motif is
      important for PNRC2 to interact with all the nuclear receptors tested. Our
      results reveal that PNRC2 has a structure and function similar to PNRC, a
      previously characterized coactivator. These two proteins represent a new type of
      nuclear receptor co-regulatory proteins.

PMID- 11574676
TI  - Crystallographic studies on damaged DNAs IV. N( 4)-methoxycytosine shows a second
      face for Watson-Crick base-pairing, leading to purine transition mutagenesis.
AB  - To investigate the mutation mechanism of purine transitions in DNA damaged with
      methoxyamine, a DNA dodecamer with the sequence d(CGCAAATTmo(4)CGCG), where
      mo(4)C is 2'-deoxy-N(4)-methoxycytidine, has been synthesized and the crystal
      structure determined by X-ray analysis. The duplex structure is similar to that
      of the original undamaged B-form dodecamer, indicating that the methoxylation
      does not affect the overall DNA conformation. Electron density maps clearly show
      that the two mo(4)C residues form Watson-Crick-type base pairs with the adenine
      residues of the opposite strand and that the methoxy groups of mo(4)C adopt the
      anti conformation to N(3) around the C(4)-N(4) bond. For the pair formation
      through hydrogen bonds the mo(4)C residues are in the imino tautomeric state.
      Together with previous work, the present work establishes that the methoxylated
      cytosine residue can present two alternate faces for Watson-Crick base-pairing,
      thanks to the amino<-->imino tautomerism allowed by methoxylation. Based on this
      property, two gene transition routes are proposed.

PMID- 11574677
TI  - Protein and DNA requirements of the bacteriophage HP1 recombination system: a
      model for intasome formation.
AB  - A fundamental step in site-specific recombination reactions involves the
      formation of properly arranged protein-DNA structures termed intasomes. The
      contributions of various proteins and DNA binding sites in the intasome determine
      not only whether recombination can occur, but also in which direction the
      reaction is likely to proceed and how fast the reaction will go. By mutating
      individual DNA binding sites and observing the effects of various mixtures of
      recombination proteins on the mutated substrates, we have begun to categorize the
      requirements for intasome formation in the site-specific recombination system of
      bacteriophage HP1. These experiments define the binding site occupancies in both
      integrative and excessive recombination for the three recombination proteins: HP1
      integrase, HP1 Cox and IHF. This data has allowed us to create a model which
      explains many of the biochemical features of HP1 recombination, demonstrates the
      importance of intasome components on the directionality of the reaction and
      predicts further ways in which the role of the intasome can be explored.

PMID- 11574678
TI  - Nuclear antisense effects of neutral, anionic and cationic oligonucleotide
      analogs.
AB  - The antisense activity of oligomers with 2'-O-methyl (2'-O-Me) phosphorothioate,
      2'-O-methoxyethyl (2'-O-MOE) phosphorothioate, morpholino and peptide nucleic
      acid (PNA) backbones was investigated using a splicing assay in which the
      modified oligonucleotides blocked aberrant and restored correct splicing of
      modified enhanced green fluorescent protein (EGFP) precursor to mRNA (pre-mRNA),
      generating properly translated EGFP. In this approach, antisense activity of each
      oligomer was directly proportional to up-regulation of the EGFP reporter. This
      provided a positive, quantitative readout for sequence-specific antisense effects
      of the oligomers in the nuclei of individual cells. Nuclear localization of
      fluorescent labeled oligomers confirmed validity of the functional assay. The
      results showed that the free uptake and the antisense efficacy of neutral
      morpholino derivatives and cationic PNA were much higher than that of negatively
      charged 2'-O-Me and 2'-O-MOE congeners. The effects of the PNA oligomers were
      observed to be dependent on the number of L-lysine (Lys) residues at the C
      terminus. The experiments suggest that the PNA containing Lys was taken up by a
      mechanism similar to that of cell-penetrating homeodomain proteins and that the
      Lys tail enhanced intracellular accumulation of PNA oligomer without affecting
      its ability to reach and hybridize to the target sequence.

PMID- 11574679
TI  - Promiscuous patching of broken chromosomes in mammalian cells with
      extrachromosomal DNA.
AB  - To study double-strand break (DSB)-induced mutations in mammalian chromosomes, we
      stably transfected thymidine kinase (tk)-deficient mouse fibroblasts with a DNA
      substrate containing a recognition site for yeast endonuclease I-SceI embedded
      within a functional tk gene. Cells were then electroporated with a plasmid
      expressing endonuclease I-SceI to induce a DSB, and clones that had lost tk
      function were selected. In a previous study of DSB-induced tk-deficient clones,
      we found that approximately 8% of recovered tk mutations involved the capture of
      one or more DNA fragments at the DSB site. Almost half of the DNA capture events
      involved the I-SceI expression plasmid, and several events involved
      retrotransposable elements. To learn whether only certain DNA sequences or motifs
      are efficiently captured, in the current work we electroporated an I-SceI
      expression plasmid along with HaeIII fragments of &phi;X174 genomic DNA. We
      report that 18 out of 132 tk-deficient clones recovered had captured DNA
      fragments, and 14 DNA capture events involved one or more fragments of &phi;X174
      DNA. Microhomology existed at most junctions between &phi;X174 DNA and genomic
      sequences. Our work suggests that virtually any extrachromosomal DNA molecule may
      be recruited for the patching of DSBs in a mammalian genome.

PMID- 11574680
TI  - Class-1 translation termination factors: invariant GGQ minidomain is essential
      for release activity and ribosome binding but not for stop codon recognition.
AB  - Previously, we have shown that all class-1 polypeptide release factors (RFs)
      share a common glycine-glycine-glutamine (GGQ) motif, which is critical for RF
      activity. Here, we subjected to site-directed mutagenesis two invariant amino
      acids, Gln185 and Arg189, situated in the GGQ minidomain of human eRF1, followed
      by determination of RF activity and the ribosome binding capacity for mutant
      eRF1. We show that replacement of Gln185 with polar amino acid residues causes
      partial inactivation of RF activity; Gln185Ile, Arg189Ala and Arg189Gln mutants
      are completely inactive; all mutants that retain partial RF activity respond
      similarly to three stop codons. We suggest that loss of RF activity for Gln185
      and Arg189 mutants is caused by distortion of the conformation of the GGQ
      minidomain but not by damage of the stop codon recognition site of eRF1. Our data
      are inconsistent with the model postulating direct involvement of Gln185 side
      chain in orientation of water molecule toward peptidyl-tRNA ester bond at the
      ribosomal peptidyl transferase centre. Most of the Gln185 mutants exhibit reduced
      ability to bind to the ribosome, probably, to rRNA and/or (peptidyl)-tRNA(s). The
      data suggest that the GGQ motif is implicated both in promoting peptidyl-tRNA
      hydrolysis and binding to the ribosome.

PMID- 11574681
TI  - PROSPECT improves cis-acting regulatory element prediction by integrating
      expression profile data with consensus pattern searches.
AB  - Consensus pattern and matrix-based searches designed to predict cis-acting
      transcriptional regulatory sequences have historically been subject to large
      numbers of false positives. We sought to decrease false positives by
      incorporating expression profile data into a consensus pattern-based search
      method. We have systematically analyzed the expression phenotypes of over 6000
      yeast genes, across 121 expression profile experiments, and correlated them with
      the distribution of 14 known regulatory elements over sequences upstream of the
      genes. Our method is based on a metric we term probabilistic element assessment
      (PEA), which is a ranking of potential sites based on sequence similarity in the
      upstream regions of genes with similar expression phenotypes. For eight of the 14
      known elements that we examined, our method had a much higher selectivity than a
      naive consensus pattern search. Based on our analysis, we have developed a web
      based tool called PROSPECT, which allows consensus pattern-based searching of
      gene clusters obtained from microarray data.

PMID- 11574682
TI  - Methylation of the nucleobases in RNA oligonucleotides mediates duplex-hairpin
      conversion.
AB  - We have systematically investigated the duplex to hairpin conversion of
      oligoribonucleotides under the aspect of nucleobase methylation. The first part
      of our study refers to the self-complementary sequence rCGCGAAUUCGCGA, which
      forms a stable Watson-Crick base paired duplex under various buffer conditions.
      It is shown that this sequence is forced to adopt a hairpin conformation if one
      of the central 6 nt is replaced by the corresponding methylated nucleotide, such
      as 1-methylguanosine N(2),N(2)-dimethylguanosine, N(6),N(6)-dimethyladenosine
      (m(6)(2)A) or 3-methyluridine. On the other hand, the duplex structure is
      retained and even stabilized by replacement of a central nucleotide with N(2)
      methylguanosine (m(2)G) or N(4)-methylcytidine. A borderline case is represented
      by N(6)-methyladenosine (m(6)A). Although generally a duplex-preserving
      modification, our data indicate that m(6)A in specific strand positions and at
      low strand concentrations is able to effectuate duplex-hairpin conversion. Our
      studies also include the ssu ribosomal helix 45 sequence motif,
      rGACCm(2)GGm(6)(2)Am(6)(2)AGGUC. In analogy, it is demonstrated that the tandem
      m(6)(2)A nucleobases of this oligoribonucleotide prevent duplex formation with
      complementary strands. Therefore, it can be concluded that nucleobase
      methylations at the Watson-Crick base pairing site provide the potential not only
      to modulate but to substantially affect RNA structure by formation of different
      secondary structure motifs.

PMID- 11574683
TI  - A computational scan for U12-dependent introns in the human genome sequence.
AB  - U12-dependent introns are found in small numbers in most eukaryotic genomes, but
      their scarcity makes accurate characterisation of their properties challenging. A
      computational search for U12-dependent introns was performed using the draft
      version of the human genome sequence. Human expressed sequences confirmed 404 U12
      dependent introns within the human genome, a 6-fold increase over the total
      number of non-redundant U12-dependent introns previously identified in all
      genomes. Although most of these introns had AT-AC or GT-AG terminal
      dinucleotides, small numbers of introns with a surprising diversity of termini
      were found, suggesting that many of the non-canonical introns found in the human
      genome may be variants of U12-dependent introns and, thus, spliced by the minor
      spliceosome. Comparisons with U2-dependent introns revealed that the U12
      dependent intron set lacks the 'short intron' peak characteristic of U2-dependent
      introns. Analysis of this U12-dependent intron set confirmed reports of a biased
      distribution of U12-dependent introns in the genome and allowed the
      identification of several alternative splicing events as well as a surprising
      number of apparent splicing errors. This new larger reference set of U12
      dependent introns will serve as a resource for future studies of both the
      properties and evolution of the U12 spliceosome.

PMID- 11574684
TI  - An active retrotransposon in Candida albicans.
AB  - Tca2 is a Ty1/copia-type retrotransposon from the pathogenic yeast Candida
      albicans. It was originally identified as an abundant, linear, extrachromosomal,
      double-stranded DNA molecule. Here we show that Tca2 is widespread in C.albicans,
      but that the abundance of extrachromosomal Tca2 DNA varies greatly among
      different strains and is strongly dependent on the growth temperature. The
      relative levels of Tca2 RNA vary in a similar pattern to the extrachromosomal
      DNA, raising the possibility that the variations in extrachromosomal DNA levels
      are introduced predominantly at the level of transcription. We have also analysed
      the retrotranspositional activity of the element by developing a transposition
      assay involving a cloned Tca2 element tagged with a selectable marker gene that
      is activated by passage through an RNA intermediate. We show that the marked Tca2
      is transpositionally active as transposed copies of the marked element became
      integrated at a variety of new positions in the genome and an intron in the donor
      element was precisely removed in the newly transposed copies. This is the first
      report of transposition in C.albicans.

PMID- 11574685
TI  - Covalent capture of a human O(6)-alkylguanine alkyltransferase-DNA complex using
      N(1),O(6)-ethanoxanthosine, a mechanism-based crosslinker.
AB  - The DNA repair protein O(6)-alkylguanine alkyltransferase (AGT) is responsible
      for removing promutagenic alkyl lesions from exocyclic oxygens located in the
      major groove of DNA, i.e. the O(6) and O(4) positions of guanine and thymine. The
      protein carries out this repair reaction by transferring the alkyl group to an
      active site cysteine and in doing so directly repairs the premutagenic lesion in
      a reaction that inactivates the protein. In order to trap a covalent AGT-DNA
      complex, oligodeoxyribonucleotides containing the novel nucleoside N(1),O(6)
      ethanoxanthosine ((e)X) have been prepared. The (e)X nucleoside was prepared by
      deamination of 3',5'-protected O(6)-hydroxyethyl-2'-deoxyguanosine followed by
      cyclization to produce 3',5'-protected N(1),O(6)-ethano-2'-deoxyxanthosine, which
      was converted to the nucleoside phosphoramidite and used in the preparation of
      oligodeoxyribonucleotides. Incubation of human AGT with a DNA duplex containing
      (e)X resulted in the formation of a covalent protein-DNA complex. Formation of
      this complex was dependent on both active human AGT and (e)X and could be
      prevented by chemical inactivation of the AGT with O(6)-benzylguanine. The
      crosslinking of AGT to DNA using (e)X occurs with high yield and the resulting
      complex appears to be well suited for further biochemical and biophysical
      characterization.

PMID- 11574686
TI  - Suppression of sterol 12alpha-hydroxylase transcription by the short heterodimer
      partner: insights into the repression mechanism.
AB  - Cholesterol conversion to bile acids is subject to a feedback regulatory
      mechanism by which bile acids down-regulate their own synthesis. This regulation
      occurs at the level of transcription of several genes encoding enzymes in the
      bile acid biosynthetic pathway. One of these enzymes is sterol 12alpha
      hydroxylase/CYP8B1 (12alpha-hydroxylase), the specific enzyme required for cholic
      acid synthesis. The levels of this enzyme determine the ratio of cholic acid to
      chenodeoxycholic acid and thus the hydrophobicity of the circulating bile acid
      pool. Previous studies from this laboratory showed that fetoprotein transcription
      factor (FTF) is required for 12alpha-hydroxylase promoter activity and bile acid
      mediated regulation. Here, we report that the short heterodimer partner (SHP)
      suppresses 12alpha-hydroxylase promoter activity via an interaction with FTF.
      Hepatic nuclear factor-4 (HNF-4) binds and activates the 12alpha-hydroxylase
      promoter and is required for 12alpha-hydroxylase promoter activity. Although HNF
      4 interacts with SHP, it is not involved in SHP-mediated suppression of 12alpha
      hydroxylase promoter activity. FTF and not HNF-4 is the factor involved in
      regulation of 12alpha-hydroxylase promoter activity by bile acids through its
      interaction with SHP. Finally, interaction of SHP with FTF displaces FTF binding
      to its sites within the 12alpha-hydroxylase promoter. These results provide
      insights into the mechanism of action of bile acid-mediated regulation of sterol
      12alpha-hydroxylase transcription.

PMID- 11574687
TI  - Specific distribution of the Saccharomyces cerevisiae linker histone homolog
      HHO1p in the chromatin.
AB  - In virtually all eukaryotic organisms, linker DNA between nucleosomes is
      associated with a histone termed linker histone or histone H1. In Saccharomyces
      cerevisiae, HHO1 encodes a putative linker histone with very significant homology
      to histone H1. The encoded protein is expressed in the nucleus, but has not been
      shown to affect global chromatin structure, nor has its deletion shown any
      detectable phenotype. In vitro chromatin assembly experiments with recombinant
      HHO1p have shown that it is able to complex with dinuncleosomes in a similar
      manner to histone H1. Here we report that while disruption of HHO1 has little
      affect on RNA levels of most cellular transcripts, there are numerous exceptions.
      Measurement of HHO1p concentration in the wild-type cell showed a stoichiometry
      of about one HHO1p molecule per 37 nucleosomes. Localization of HHO1p in the
      chromatin, using an immunoprecipitation technique, showed preferential HHO1p
      binding to rDNA sequences. These results suggest that HHO1p may play a similar
      role to linker histones, but at restricted locations in the chromatin.

PMID- 11574688
TI  - Psoralen-modified clamp-forming antisense oligonucleotides reduce cellular c-Myc
      protein expression and B16-F0 proliferation.
AB  - The c-myc protooncogene plays an important role in the abnormal growth pattern of
      melanoma cells. In an attempt to inhibit c-Myc expression and the growth of an
      established murine melanoma cell line, we targeted homopurine sequences within
      the mouse myc mRNA with modified antisense oligonucleotides (AS ODNs). Psoralen
      was conjugated to the 5'-end of these clamp-forming oligonucleotides (clamp
      ODNs). Gel mobility shift analysis demonstrated a sequence-specific interaction
      between the active clamp ODNs (Myc-E2C and Myc-E3C) and the 1.4 kb c-myc mRNA,
      but no interaction with the control clamp ODN (SCR**). This association was
      further confirmed by thermal denaturation studies. In vitro translation assays
      demonstrated that both Myc-E2C and Myc-E3C at 5 microM inhibited c-Myc expression
      >99% after UV activation at 366 nm. Immunostaining of B16-F0 cells with a c-Myc
      monoclonal antibody revealed a significant reduction in c-Myc after clamp ODN
      treatment compared with the untreated or SCR** control-treated cells. This result
      was corroborated by western blot analysis. Utilizing the MTT assay to determine
      the effects of ODN-mediated c-Myc reduction on B16-F0 growth, we observed 60 and
      64% reductions in growth after treatment with 5 microM Myc-E3C and Myc-E2C,
      respectively. We attribute the enhanced effectiveness of the clamp ODNs to
      psoralen activation. Our preliminary data suggest that inhibiting c-Myc
      overexpression results in a significant reduction in abnormal proliferation of
      B16-F0 melanoma cells and that the increased efficiency of clamp ODNs may provide
      an important advantage for their use in antisense therapies.

PMID- 11574689
TI  - New chemically reactive dsDNAs containing single internucleotide
      monophosphoryldithio links: reactivity of 5'-mercapto-oligodeoxyribonucleotides.
AB  - Novel modified DNA duplexes with single bridging 5'-SS-monophosphoryldithio links
      [-OP(=O)-O(-)-SS-CH(2)-] were synthesized by autoligation of an oligonucleotide
      3'-phosphorothioate and a 5'-mercapto-oligonucleotide previously converted to a 2
      pyridyldisulfide adduct. Monophosphoryldisulfide link formation is not a
      stringent template-dependent process under the conditions used and does not
      require strong binding of the reactive oligomers to the complementary strand. The
      modified internucleotide linkage, resembling the natural phosphodiester bond in
      size and charge density, is stable in water, easily undergoes thiol-disulfide
      exchange and can be specifically cleaved by the action of reducing reagents. DNA
      molecules containing an internal -OP(=O)-O(-)-SS-CH(2)- bridge are stable to
      spontaneous exchange of disulfide-linked fragments (recombination) even in the
      single-stranded state and are promising reagents for autocrosslinking with
      cysteine-containing proteins. The chemical and supramolecular properties of
      oligonucleotides with 5'-sulfhydryl groups were further characterized. We have
      shown that under the conditions of chemical ligation the 5'-SH group of the
      oligonucleotide has a higher reactivity towards N-hydroxybenzotriazole-activated
      phosphate in an adjacent oligonucleotide than does the OH group. This
      autoligation, unlike disulfide bond formation, proceeds only in the presence of
      template oligonucleotide, necessary to provide the activated phosphate in close
      proximity to the SH-, OH- or phosphate function.

PMID- 11574690
TI  - Activation of the human PAX6 gene through the exon 1 enhancer by transcription
      factors SEF and Sp1.
AB  - PAX6 is a transcription factor that plays a major role in ocular morphogenesis.
      PAX6 is expressed in the eye, central nervous system and pancreas. Two
      alternative promoters, P0 and P1, which are differentially regulated during
      development, drive PAX6 transcription. We identified a 57 bp cis-regulatory
      element in exon 1 of the human PAX6 gene exon 1 enhancer (EIE). EIE enhances P1
      driven PAX6 expression. Three regions in E1E (E1E-1, E1E-2 and E1E-3) have
      sequence similarities with binding sites of transcription factors ARP-1, Isl-1
      and SEF, respectively. As shown by electrophoretic mobility shift assays, E1E-3,
      but not E1E-1 or E1E-2, bound to proteins in nuclear extracts of human glioma
      cells and transcription factor SEF bound to E1E-3. As shown by transient
      transfection experiments, deletion or site-specific mutations in E1E-3
      dramatically decreased P1 promoter activity. Mutations in E1E-2, however, did not
      affect function of the P1 promoter. Co-transfection of SEF and PAX6 promoter
      reporter constructs showed that SEF up-regulates PAX6 gene expression through the
      P1 promoter. Two Sp1 sites in the E1E region were also shown to be important by
      transient co-transfection assays. Data from immunoprecipitation and transient
      transfection assays demonstrated that SEF and Sp1 interacted in vitro and may act
      together in vivo to regulate PAX6 expression.

PMID- 11574691
TI  - Identification and characterisation of a developmentally regulated mammalian gene
      that utilises -1 programmed ribosomal frameshifting.
AB  - Translational recoding of mRNA through a -1 ribosomal slippage mechanism has been
      observed in RNA viruses and retrotransposons of both eukaryotes and prokaryotes.
      Whilst this provides a potentially powerful mechanism of gene regulation, the
      utilization of -1 translational frameshifting in regulating mammalian gene
      expression has remained obscure. Here we report a mammalian gene, Edr, which
      provides the first example of -1 translational recoding in a eukaryotic cellular
      gene. In addition to bearing functional frameshift elements that mediate
      expression of distinct polypeptides, Edr bears both CCHC zinc-finger and putative
      aspartyl protease catalytic site retroviral-like motifs, indicative of a relic
      retroviral-like origin for Edr. These features, coupled with conservation of Edr
      as a single copy gene in mouse and man and striking spatio-temporal regulation of
      expression during embryogenesis, suggest that Edr plays a functionally important
      role in mammalian development.

PMID- 11574692
TI  - Comparison between CUUG and UUCG tetraloops: thermodynamic stability and
      structural features analyzed by UV absorption and vibrational spectroscopy.
AB  - CUUG loop is one of the most frequently occurring tetraloops in bacterial 16S
      rRNA. This tetraloop has a high thermodynamic stability as proved by previous UV
      absorption and NMR experiments. Here, we present our results concerning the
      thermodynamic and structural features of the 10mer 5'-r(GCG-CUUG-CGC)-3', forming
      a highly stable CUUG tetraloop hairpin in aqueous solution, by means of several
      optical techniques (UV and FT-IR absorption, Raman scattering). UV melting
      profile of this decamer provides a high melting temperature (60.7 degrees C). A
      set of Raman spectra recorded at different temperatures allowed us to analyze the
      order-to-disorder (hairpin-to-random coil) transition. Assignment of vibrational
      markers led us to confirm the particular nucleoside conformation, and to get
      information on the base stacking and base pairing in the hairpin structure.
      Moreover, comparison of the data obtained from two highly stable CUUG and UUCG
      tetraloops containing the same nucleotides but in a different order permitted an
      overall discussion of their structural features on the basis of Raman marker
      evidences.

PMID- 11574693
TI  - Sugar additives for MALDI matrices improve signal allowing the smallest
      nucleotide change (A:T) in a DNA sequence to be resolved.
AB  - Sample preparation for matrix-assisted laser desorption/ionization (MALDI) mass
      spectrometry (MS) of DNA is critical for obtaining high quality mass spectra.
      Sample impurity, solvent content, substrate surface and environmental conditions
      (temperature and humidity) all affect the rate of matrix-analyte co
      crystallization. As a result, laser fluence threshold for desorption/ionization
      varies from spot to spot. When using 3-hydroxypicolinic acid (3-HPA) as the
      matrix, laser fluence higher than the threshold value reduces mass resolution in
      time-of-flight (TOF) MS as the excess energy transferred to DNA causes metastable
      decay. This can be overcome by either searching for 'hot' spots or adjusting the
      laser fluence. However, both solutions may require a significant amount of
      operator manipulation and are not ideal for automatic measurements. We have added
      various sugars for crystallization with the matrix to minimize the transfer of
      excess laser energy to DNA molecules. Fructose and fucose were found to be the
      most effective matrix additives. Using these additives, mass resolution for DNA
      molecules does not show noticeable deterioration as laser energy increases.
      Improved sample preparation is important for the detection of single nucleotide
      polymorphisms (SNPs) using primer extension with a single nucleotide. During
      automatic data acquisition it is difficult to routinely detect heterozygous A/T
      mutations, which requires resolving a mass difference of 9 Da, unless a sugar is
      added during crystallization.

PMID- 11574694
TI  - DNA microarrays with stem-loop DNA probes: preparation and applications.
AB  - We have developed DNA microarrays containing stem-loop DNA probes with short
      single-stranded overhangs immobilized on a Packard HydroGel chip, a 3-dimensional
      porous gel substrate. Microarrays were fabricated by immobilizing self
      complementary single-stranded oligonucleotides, which adopt a partially duplex
      structure upon denaturing and re-annealing. Hybridization of single-stranded DNA
      targets to such arrays is enhanced by contiguous stacking interactions with stem
      loop probes and is highly sequence specific. Subsequent enzymatic ligation of the
      targets to the probes followed by stringent washing further enhances the
      mismatched base discrimination. We demonstrate here that these microarrays
      provide excellent specificity with signal-to-background ratios of from 10- to 300
      fold. In a comparative study, we demonstrated that HydroGel arrays display 10-30
      times higher hybridization signals than some solid surface DNA microarrays. Using
      Sanger sequencing reactions, we have also developed a method for preparing nested
      3'-deletion sets from a target and evaluated the use of stem-loop DNA arrays for
      detecting p53 mutations in the deletion set. The stem-loop DNA array format is
      simple, robust and flexible in design, thus it is potentially useful in various
      DNA diagnostic tests.

PMID- 11574695
TI  - Quantitative detection of single nucleotide polymorphisms for a pooled sample by
      a bioluminometric assay coupled with modified primer extension reactions
      (BAMPER).
AB  - A new method for SNP analysis based on the detection of pyrophosphate (PPi) is
      demonstrated, which is capable of detecting small allele frequency differences
      between two DNA pools for genetic association studies other than SNP typing. The
      method is based on specific primer extension reactions coupled with PPi
      detection. As the specificity of the primer-directed extension is not enough for
      quantitative SNP analysis, artificial mismatched bases are introduced into the 3'
      terminal regions of the specific primers as a way of improving the switching
      characteristics of the primer extension reactions. The best position in the
      primer for such artificial mismatched bases is the third position from the primer
      3'-terminus. Contamination with endogenous PPi, which produces a large background
      signal level in SNP analysis, was removed using PPase to degrade the PPi during
      the sample preparation process. It is possible to accurately and quantitatively
      analyze SNPs using a set of primers that correspond to the wild-type and mutant
      DNA segments. The termini of these primers are at the mutation positions. Various
      types of SNPs were successfully analyzed. It was possible to very accurately
      determine SNPs with frequencies as low 0.02. It is very reproducible and the
      allele frequency difference can be determined. It is accurate enough to detect
      meaningful genetic differences among pooled DNA samples. The method is sensitive
      enough to detect 14 amol ssM13 DNA. The proposed method seems very promising in
      terms of realizing a cost-effective, large-scale human genetic testing system.

PMID- 11574696
TI  - C-SPACE (cleavage-specific amplification of cDNA ends): a novel method of
      ribozyme-mediated gene identification.
AB  - A hairpin ribozyme, RzCR2A, directed against position 323 of the hepatitis C
      virus 5'-untranslated region (HCV 5'-UTR) was used to establish and validate a
      novel method for the detection of cellular target molecules for hairpin
      ribozymes, termed C-SPACE (cleavage-specific amplification of cDNA ends). For C
      SPACE, HeLa mRNA containing the transcript of interest was subjected to in vitro
      cleavage by RzCR2A in parallel with a control ribozyme, followed by reverse
      transcription using a modified SMART cDNA amplification method and cleavage
      specific PCR analysis. C-SPACE allowed identification of the RzCR2A target
      transcript from a mixture containing the entire cellular mRNA while only
      requiring knowledge of the ribozyme binding sequence for amplification. In a
      similar approach, C-SPACE was used successfully to identify human 20S proteasome
      alpha-subunit PSMA7 mRNA as the cellular target RNA of Rz3'X, a ribozyme
      originally designed to cleave the negative strand HCV 3'-UTR. Rz3'X was found to
      substantially inhibit HCV internal ribosome entry site (IRES) activity and PSMA7
      was subsequently confirmed to be involved in HCV IRES-mediated translation.
      Thereby, C-SPACE was validated as a powerful tool to rapidly identify unknown
      target RNAs recognized and cleaved by hairpin ribozymes.

PMID- 11574697
TI  - Molecular indexing of human genomic DNA.
AB  - Molecular indexing sorts DNA fragments into subsets for inter-sample comparisons.
      Type IIS or interrupted palindrome restriction endonucleases, which result in
      single-stranded ends not including the original recognition sequence of the
      enzyme, are used to produce the fragments. The ends can then be any sequence but
      will always be specific for a given fragment. Fragments with particular ends are
      selected by ligation to a corresponding indexing adapter. We describe iterative
      indexing, a new process that after an initial round of indexing uses a Type IIS
      restriction endonuclease to expose additional sequence for further indexing. New
      plasmids, pINDnn, were produced for novel use as indexing adapters. Together, the
      plasmids index all 16 possible dinucleotides. Their large size can be increased
      by dimerisation in vitro and allows the isolation of indexed material by size
      separation. Fragments produced from human genomic DNA by Type II restriction
      endonucleases were sorted using six bases in total to a possible enrichment of
      1920-fold. By comparison with the public human sequence databases, fidelity of
      indexing was shown to be high and was tolerant of repetitive sequences. Genome
      wide comparisons on a candidate or non-candidate basis are made possible by this
      approach.

PMID- 11574698
TI  - The ageism survey: first findings.
AB  - PURPOSE: To develop an instrument that can be used to answer three questions:
      What is the prevalence of ageism in various societies? Which types of ageism are
      more prevalent? Which subgroups of older people report more ageism? METHODS: A
      survey instrument was developed listing 20 types of ageism. This instrument was
      tested on a convenience sample of 84 persons older than age 60. RESULTS: The
      instrument appears to have satisfactory reliability and validity. The survey
      found that the experience of ageism was widespread and frequent among these
      respondents. The majority reported several incidents of ageism and over half of
      the incidents were reported to have occurred "more than once." The most frequent
      types were persons showing disrespect for older people, followed by persons
      showing assumptions about ailments or frailty caused by age. IMPLICATIONS:
      Researchers now have a reliable and valid instrument for measuring the prevalence
      of ageism in various societies and of various types of ageism experienced by
      various groups of older persons. This may aid in reducing the prevalence of
      ageism in our society.

PMID- 11574699
TI  - The complex nature of ageism: what is it? Who does it? Who perceives it?

PMID- 11574700
TI  - Eradication of ageism requires addressing the enemy within.

PMID- 11574702
TI  - Should disability items in the census be used for planning services for elders?
AB  - PURPOSE: The main goal of this study was to determine how well the disability
      questions of both the 1990 and 2000 Census correlated with a standard measure of
      disability. If the census questions were to correlate moderately well with a
      standard measure of disability, then Area Agencies on Aging (AAA) and other
      organizations would be able to use census information in estimating service needs
      for their catchment (service) area. DESIGN AND METHODS: Questionnaires containing
      both the census disability questions and a standard measure of disability were
      mailed to 4,508 older adults; 1,514 completed surveys were returned. In order to
      assess reliability, 472 of the respondents who completed the mail survey were
      reinterviewed by phone. All three disability measures were collapsed into the
      following three categories: no needs, instrumental activities of daily living
      (IADL) needs only, and activities of daily living (ADL) needs. RESULTS: All three
      disability measures exhibited moderate to good test-retest reliability. Using a
      standard measure of disability as the criterion, validity for the 1990 Census
      measure was quite low (Kappas of approximately 0.35). Validity for the 2000
      Census measure was moderate to good (Kappas of approximately 0.60). IMPLICATIONS:
      These results suggest that the 2000 Census disability questions may be
      sufficiently valid for planning purposes. However, additional research with more
      representative samples of older adults is needed.

PMID- 11574703
TI  - Resident contact with family and friends following nursing home admission.
AB  - PURPOSE: This study explored factors that are related to the level of contact
      (number of visits and calls) between newly admitted nursing home residents and
      their family and friends. In addition to reexamining factors studied previously,
      several new factors were explored: contact level prior to nursing home placement,
      dementia status, and resident race. DESIGN AND METHODS: Interviews were conducted
      with the significant others of 1,441 residents from a representative sample of
      nursing homes in Maryland. RESULTS: Contact decreased by approximately half
      following admission, compared to reported preadmission contact. Rates of contact
      are positively related to nonuse of Medicaid, kinship closeness, support network
      proximity, nondemented status, and White race. After controlling for preadmission
      contact, postadmission contact is positively associated with kinship closeness,
      support network proximity, nondemented status, and White race. IMPLICATIONS: The
      study identifies factors that are useful to consider when designing interventions
      to increase family involvement with nursing home residents.

PMID- 11574704
TI  - State Medicaid nursing home reimbursement rates: adjusting for ancillaries.
AB  - PURPOSE: State variation in inclusion of ancillary services in daily Medicaid
      nursing home reimbursement rates, versus covering ancillary costs outside of such
      rates, makes rate comparisons difficult. The purpose of this study is to adjust
      for inclusion of ancillaries when comparing Medicaid rates across states. DESIGN
      AND METHODS: Data for 1987-1998 were drawn from a national survey of Medicaid
      reimbursement. Employing a random-effects model, the PANEL option in the LIMDEP
      software was used to estimate effects on state average Medicaid nursing facility
      constant-dollar rates of the inclusion in those rates of a set of ancillaries:
      physical therapy, occupational therapy, prescription drugs, nonprescription
      drugs, durable medical equipment (DME), medical supplies, and physician services.
      RESULTS: Rates averaged higher when they included occupational therapy, physician
      services, nonprescription drugs, and both DME and medical supplies. Adjusting for
      the inclusion of ancillaries leads to a much different ranking of states than for
      unadjusted rates. IMPLICATIONS: Public and industry policy makers should consider
      the inclusion of ancillaries in rates when considering the relative adequacy of
      rates across states.

PMID- 11574705
TI  - The identification of residents capable of accurately describing daily care:
      implications for evaluating nursing home care quality.
AB  - PURPOSE: The goal of this study was to develop a method of identifying
      incontinent nursing home (NH) residents capable of providing accurate interview
      information about daily NH care. DESIGN AND METHODS: In 177 incontinent NH
      residents from four facilities, selected Minimum Data Set (MDS) ratings were
      compared with two standardized, performance-based, cognitive screening
      instruments to predict which residents could accurately answer questions
      concerning receipt of daily incontinence and mobility care practices. RESULTS:
      MDS ratings of activity of daily living performance and cognition significantly
      predicted residents' ability to accurately describe daily care practices.
      Performance-based measures of cognitive functioning did not outperform the MDS
      ratings. Selecting residents who scored two or more on four orientation items
      composing the MDS Recall subscale identified residents capable of accurately
      describing daily care practices with a sensitivity of 64% and a specificity of
      75%. IMPLICATIONS: The MDS-based criteria identified are a promising, objective
      method for selecting incontinent NH residents for interview to verify the
      occurrence of specific daily care practices.

PMID- 11574706
TI  - Analysis of key decision-making incidents in the life of a nursing home resident.
AB  - PURPOSE: This study examined change in the decision-making autonomy of a single
      nursing facility resident. DESIGN AND METHODS: This case analysis was part of a
      larger 3-year ethnographic investigation of decision-making events in four
      nursing facilities. In this case analysis, the resident, her daughter, and three
      staff members closely associated with the resident's care were each interviewed
      five times over a 15-month period. RESULTS: Analysis of interview transcripts
      revealed four themes in decision making. Temporal change was evident in a complex
      scenario regarding room changes. Spatial context reflected the need for
      predictability and adaptability in decisions using space. Interdependence of
      decisions and decision makers was most evident with medical treatment and health
      care decisions. Awareness, being informed, and knowing what was going on was the
      final theme. IMPLICATIONS: Despite having the best interests of the resident in
      mind, the process of decision making in nursing facilities may contribute to a
      pattern of gradual withdrawal of decisional autonomy from residents regardless of
      their ability to make decisions.

PMID- 11574707
TI  - Measuring resident satisfaction in residential aged care.
AB  - PURPOSE: The aims of this study were to assess the factor structure, reliability,
      and validity of an existing Resident Satisfaction Questionnaire (RSQ) and to
      develop a short-form RSQ for regular use in residential aged care settings.
      DESIGN AND METHODS: A cross-sectional survey design was adopted to collect the
      required information, with facilities being selected using stratified random
      sampling. Both exploratory and confirmatory factor analyses were conducted on a
      sample of 1,146 residents in 70 residential aged care facilities in Western
      Australia. RESULTS: The RSQ is confirmed to be a reliable, valid, context
      relevant, and easy-to-use instrument for assessing residents' satisfaction with
      their residential aged care facilities. Resident satisfaction, as assessed via
      the RSQ, was found to be a multidimensional construct comprising six factors
      Room, Home, Social Interaction, Meals Service, Staff Care, and Involvement.
      IMPLICATIONS: A 24-item short version of the RSQ can be constructed based on the
      six-factor resident satisfaction measurement model and used as a regular
      monitoring tool of resident satisfaction for quality improvement purposes.

PMID- 11574708
TI  - Age, consumer direction, and outcomes of supportive services at home.
AB  - PURPOSE: Supportive services at home are essential for older people with severe
      chronic impairments. Newer "consumer-directed" models of organizing home-based
      services rely heavily on service recipients rather than home care agencies to
      arrange and direct care at home. This study examined differences in service
      experience and outcomes between recipients over and under age 65 who direct their
      own services in one large Medicaid program. DESIGN AND METHODS: A random sample
      of 1,095 recipients of In-Home Supportive Services in California was selected and
      interviewed by telephone. Interviews were conducted in English, Spanish, and
      three Asian languages; those with severe cognitive impairment were excluded from
      the study. RESULTS: Findings indicate that although younger recipients embrace
      self-direction more enthusiastically than older ones, age differences are small
      on a majority of service outcomes. On average, older users embrace this model and
      manage within it much like younger users. Some differences emerge between the
      young-old (65-74) and old-old (75+), but these are neither consistent nor
      determinative. IMPLICATIONS: Old age is far from an inevitable barrier to self
      direction. As with other age groups, there are opportunities and obstacles to be
      addressed as this newer approach to home care is disseminated.

PMID- 11574709
TI  - Profile of discrete emotions in affective disorders in older primary care
      patients.
AB  - PURPOSE: This research examined whether the frequencies of specific emotions are
      associated with major and minor depression in older primary care patients. DESIGN
      AND METHODS: Older primary care patients (N = 146), prescreened with a depression
      questionnaire, completed a diagnostic interview and an emotions questionnaire.
      RESULTS: Controlling for age, sex, and other psychiatric and medical illnesses,
      major depressives differed from nondepressed controls in nine emotions; minor
      depressives differed from controls in four emotions. Major depressives differed
      from the controls more in sadness, joy, and interest--but not anger, fear, or
      guilt--than in comparison sets of emotions. Minor depressives differed from the
      controls more in sadness and inner-directed hostility--but not guilt, anger,
      fear, joy, or interest--than in comparison sets of emotions. IMPLICATIONS: The
      frequencies of discrete emotions are differentially associated with major and
      minor depression; future research is needed to determine their specific
      diagnostic and treatment implications.

PMID- 11574710
TI  - The Zarit Burden Interview: a new short version and screening version.
AB  - PURPOSE: The purpose of the study was to develop a short and a screening version
      of the Zarit Burden Interview (ZBI) that would be suitable across diagnostic
      groups of cognitively impaired older adults, and that could be used for cross
      sectional, longitudinal, and intervention studies. DESIGN AND METHODS: We used
      data from 413 caregivers of cognitively impaired older adults referred to a
      memory clinic. We collected information on caregiver burden with the 22-item ZBI,
      and information about dependence in activities of daily living (ADLs) and the
      frequency of problem behaviors among care recipients. We used factor analysis and
      item-total correlations to reduce the number of items while taking into
      consideration diagnosis and change scores. RESULTS: We produced a 12-item version
      (short) and a 4-item version (screening) of the ZBI. Correlations between the
      short and the full version ranged from 0.92 to 0.97, and from 0.83 to 0.93 for
      the screening version. Correlations between the three versions and ADL and
      problem behaviors were similar. We further investigated the behavior of the short
      version with a two-way analysis of variance and found that it produced identical
      results to the full version. IMPLICATIONS: The short and screening versions of
      the ZBI produced results comparable to those of the full version. Reducing the
      number of items did not affect the properties of the ZBI, and it may lead to
      easier administration of the instrument.

PMID- 11574711
TI  - A comprehensive, stage-sensitive model of grief in dementia caregiving.
AB  - PURPOSE: Grief is an overlooked but important element of the caregiver
      experience. This study defines a model of caregiver grief to aid in clinical
      intervention and to support further research. DESIGN AND METHODS: This study
      addressed the grief responses of 87 spouse and adult-child caregivers of patients
      with progressive dementia representing mild, moderate, severe, and postdeath.
      Questionnaire data and qualitative findings from 16 semistructured focus group
      interviews provide the basis for a descriptive model of anticipatory grief in
      dementia caregiving. RESULTS: Significant differences emerged between spouse and
      adult-child caregiver groups as a whole and as a function of Clinical Dementia
      Rating impairment level. Caregiver grief was found to fluctuate between
      intellectual, affective, and existential poles depending upon current care
      demands and expectations. IMPLICATIONS: These findings suggest that anticipatory
      grief in dementia caregiving is "real" grief, equivalent in intensity and breadth
      to death-related grief.

PMID- 11574712
TI  - Development of a test of physical performance for the nursing home setting.
AB  - PURPOSE: This study was undertaken to develop a performance-based instrument to
      measure a range of function present among nursing home (NH) residents and to
      establish the reliability and validity of the measures. DESIGN AND METHODS:
      Fourteen items integral to daily life in a NH setting were administered to 95 NH
      residents with sufficient cognitive ability to follow a one-step command at
      baseline, 1 week later, and 6 months later. Intraclass correlation coefficients
      and Cronbach's coefficient alpha were calculated for reliability estimates. The
      Minimum Data Set (MDS), Katz, and Multidimensional Observational Scale for
      Elderly Subjects (MOSES) were used to establish concurrent validity. Factor
      analysis, correlation matrices, and other objective criteria were used for item
      reduction. RESULTS: Test-retest reliability for items ranged between.73 and.93.
      Factor analysis and correlations between Nursing Home Physical Performance Test
      (NHPPT) items and scales with measures of activities of daily living (ADL)
      suggest that the NHPPT taps aspects of gross motor function (Factor 1) and fine
      motor coordination and task sequencing (Factor 2) required for ADL function and
      mobility. The NHPPT may also tap aspects of ADL function and mobility not
      measured by the MDS (r = -.72-.75), MOSES (r = -.82-.84), or Katz (r = -.75-.77)
      scales. Effect sizes based on mean change scores were larger for the NHPPT scales
      (.38-.53) than for the other functional scales (.27-.33). IMPLICATIONS: The NHPPT
      is a reliable performance-based instrument that discriminates among frail NH
      residents. Further studies are necessary to assess the value of this instrument
      for prediction and monitoring of functional status in the NH.

PMID- 11574713
TI  - Assessing need for intensive case management in long-term care.
AB  - This article presents a brief screening tool to help case managers identify
      clients in a home- and community-based services (HCBS) program who need more
      intensive social work case management (CM). Using existing data from a case
      management time study (N = 242) and a content analysis of 70 cases in a Medicaid
      waiver-funded HCBS program, this study highlights a number of issues, such as
      dementia-related behavior problems, noncompliance with treatment, poor informal
      caregiver health and mental health, and a conflicted or problematic relationship
      between client and caregiver, which are useful in predicting need for intensive
      case management. Kappas for interrater reliability and t tests for discriminant
      validity show these items to be reliable and valid. This tool will allow for
      better allocation of CM resources in terms of case manager time and type of
      expertise needed to address these issues.

PMID- 11574714
TI  - Medicaid long-term care expenditures in Fiscal Year 2000.

PMID- 11574715
TI  - Longevity news and trends in the United States and abroad.

PMID- 11574717
TI  - Phosphate tungsten bronze series: crystallographic and structural properties of
      low-dimensional conductors.
AB  - Phosphate tungsten bronzes have been shown to be conductors of low
      dimensionality. A review of the crystallographic and structural properties of
      this huge series of compounds is given here, corresponding to the present
      knowledge of the different X-ray studies and electron microscopy investigations.
      Three main families are described, monophosphate tungsten bronzes,
      Ax(PO2)4(WO3)2m, either with pentagonal tunnels (MPTBp) or with hexagonal tunnels
      (MPTBh), and diphosphate tungsten bronzes, Ax(P2O4)2(WO3)2m, mainly with
      hexagonal tunnels (DPTBh). The general aspect of these crystal structures may be
      described as a building of polyhedra sharing oxygen corners made of regular
      stacking of WO3-type slabs with a thickness function of m, joined by slices of
      tetrahedral PO4 phosphate or P2O7 diphosphate groups. The relations of the
      different slabs with respect to the basic perovskite structure are mentioned. The
      structural description is focused on the tilt phenomenon of the WO6 octahedra
      inside a slab of WO3-type. In this respect, a comparison with the different
      phases of the WO3 crystal structures is established. The various modes of tilting
      and the different possible connections between two adjacent WO3-type slabs
      involve a great variety of structures with different symmetries, as well as the
      existence of numerous twins in MPTBp's. Several phase transitions, with the
      appearance of diffuse scattering and modulation phenomena, were analysed by X-ray
      scattering measurements and through the temperature dependence of various
      physical properties for the MPTBp's. The role of the W displacements within the
      WO3-type slabs, in two modulated structures (m = 4 and m = 10), already solved,
      is discussed. Finally, the complexity of the structural aspects of DPTBh's is
      explained on the basis of the average structures which are the only ones solved.

PMID- 11574718
TI  - Ab initio determination of the valence electron distribution in the average
      structure of the incommensurately modulated calaverite AuTe2.
AB  - The valence-electron density distribution of the average structure of
      incommensurately modulated calaverite, AuTe2, has been computed using density
      functional theory. High-density regions, centered around the Au and Te atoms, are
      not spheric, but present charge concentrations along the Au-Te and Te-Te bonds.
      The electronic band structure and its corresponding density of states reveal the
      presence of three electronic band groups, constituted mainly by Te 5s, Au 5d and
      hybrids of Te 6p + Au 6s + Au 5d orbitals. The electrons belonging to the last
      block are responsible for the chemical bonds.

PMID- 11574719
TI  - Experimental electron density in the triclinic phase of Co2(CO)6(mu-CO)(mu
      C4O2H2) at 120 K.
AB  - The experimental electron density (ED) of the triclinic phase of Co2(CO)6(mu
      CO)(mu-C4O2H2), mu-carbonyl-mu-5-oxo-2,5-dihydrofuran-2-ylbis(tricarbonylcobalt),
      has been determined through X-ray diffraction at 120 K. The presence of a 'closed
      shell' Co-Co bond in the title compound, found in an experimental ED study of its
      orthorhombic form, is confirmed by the Quantum Theory of Atoms in Molecules.
      However, the two phases show a significant Co-Co bond length difference
      [triclinic: 2.4402 (2) A; orthorhombic: 2.4222 (3) A]. The flat distribution of
      the experimental ED along the Co-Co bond path and on the two Co2C rings allows
      for variations of the Co-Co bond length which may be easily induced by the
      different packing arrangements of the two forms.

PMID- 11574720
TI  - A pentagonal cluster in certain approximants to decagonal quasicrystals.
AB  - A certain pentagonal cluster occurring in several approximants to the decagonal
      quasicrystal is discussed. The term 'cluster' is used here to denote a structure
      motif which is a certain assemblage of coordination polyhedra. The cluster
      resembles a wheel with an 'axis' and a 'tyre'. It is built up of seven intergrown
      icosahedra. The 'wheel cluster' builds up structures of infinite strands or nets
      perpendicular to the pentagonal wheel cluster axis. The wheel cluster is the main
      constituent of the decagonal approximant structure types Al3Mn, Al60Mn11Ni4 and
      Ga137Mn123.

PMID- 11574721
TI  - Charge distribution as a tool to investigate structural details. II. Extension to
      hydrogen bonds, distorted and hetero-ligand polyhedra.
AB  - It is shown that one of the main reasons for most failures of the methods for
      calculating distance-dependent bond strengths is related to the distortion of the
      coordination polyhedra. The charge distribution (CD) method which depends on only
      one universal empirical parameter (contraction parameter) is modified to include:
      (i) an iterative calculation of the effective coordination number (ECoN), to deal
      with structures containing very distorted coordination polyhedra; (ii) a specific
      contraction parameter to treat structures containing any type of hydrogen bond;
      (iii) scale factors for coordination subshells, to treat structures with hetero
      ligand polyhedra. The contraction parameter for the hydrogen bonds was obtained
      from 119 well refined structures based on neutron diffraction data. Examples of
      the application of the iterative charge distribution (CD-IT) are presented to
      show the efficiency of the new method in dealing with distorted (including
      hydrogen bonding) and hetero-ligand polyhedra. In particular, analysis of a
      series of 74 structures with pentacoordinated cations shows that deviations from
      overall trends are related to structure instability. The possible failure of the
      method with polyionic structures and 'dynamic' structures is discussed.

PMID- 11574722
TI  - Bulk modulus and non-uniform compression of Nb3Te4 and InxNb3Te4 (x < 1) channel
      compounds.
AB  - The crystal structures of Nb3Te4 and InxNb3Te4 [x = 0.539 (4)] are reported for a
      series of pressures between 0 and 40 GPa. Both compounds crystallize in space
      group P6(3)/m with a = b = 10.671 and c = 3.6468 A for Nb3Te4, and a = b = 10.677
      and c = 3.6566 A for InxNb3Te4 at ambient conditions. Phase transitions were not
      observed. High-pressure X-ray powder diffraction was measured using a diamond
      anvil cell and synchrotron radiation. Full Rietveld refinements provided the
      values of the lattice parameters and the values of the atomic coordinates at each
      pressure. The bulk modulus is found as K(0) = 70 (5) GPa for Nb3Te4 and as K(0) =
      73 (4) GPa for InxNb3Te4. The analysis of the pressure dependences of the
      detailed crystal structures shows that the compression along c involves the
      folding up of the quasi-one-dimensional zigzag chains of Nb. The compression
      perpendicular to c is entirely due to the reduction of the diameter of the
      channels. The presence of intercalated In atoms is found to have hardly any
      influence on the compression behaviour up to 40 GPa.

PMID- 11574723
TI  - Disordered crystal structure of pentamethylcyclopentadienylsodium as seen by high
      resolution X-ray powder diffraction.
AB  - The crystal structure of pentamethylcyclopentadienylsodium, [NaC10H15] (NaCp*),
      has been determined from high-resolution X-ray powder diffraction. The compound
      crystallizes in space group Cmcm with lattice parameters a = 4.61030 (3), b =
      16.4621 (3), c = 14.6751 (2) A, V = 1113.77 (4) A(3) (Z = 4). NaCp* forms
      polymeric multidecker chains along the a axis. The Rietveld refinement (R(p) =
      0.050 and R(F) = 0.163) shows that the Cp* moieties occupy, with disorder, two
      different orientations rotated away from the eclipsed conformation by +/-13.8
      degrees.

PMID- 11574724
TI  - Perchlorophenalenyl radical, C13Cl9: a modulated structure with nine threefold
      symmetric molecules in the asymmetric unit.
AB  - The odd-alternant perchlorophenalenyl radical, C13Cl9, forms molecular stacks
      centered on crystallographic threefold rotation axes, but the spacing within the
      stacks (3.78 A) is too large to allow good overlap of the orbitals in which the
      spin density is localized. The radical is ruffled because of the intramolecular
      repulsions between alpha Cl atoms (the Cl...Cl peri interactions); the average
      displacement of an alpha Cl atom from the molecular plane is approximately 0.7 A.
      The deviations from molecular planarity do not, however, determine the spacing
      within the stacks, which is determined instead by interactions between stacks.
      The modulations found in the P3c1 superstructure are a response to the short
      interstack contacts that would occur in the average pseudocell structure (R3;m,
      c' = c/6). The primary modulation is a pattern of enantiomeric alternation; a
      secondary modulation involves small rotations of the molecules around their
      threefold axes. The number (9) of independent molecules in the true cell is
      exceptionally large because of the conflict between the preference within the
      molecular stacks for threefold rotational symmetry and the preference in
      directions perpendicular to the stack axes for twofold alternation of
      enantiomers. The structural complexity reduces the precision of the distances and
      angles determined, but the average values found are in excellent agreement with
      those calculated by density functional theory.

PMID- 11574725
TI  - Determination of the structure of 2(benzene-1,3,5-tricarboxylic acid)-1.5(pyrene)
      2(methanol) and comparison with that of 2(benzene-1,3,5-tricarboxylic acid)
      pyrene-2(ethanol).
AB  - The structure of the title methanol complex (P1;, Z = 2) has been determined and
      compared with that of the title ethanol complex (C2/c, Z = 8) using published
      data. Both complexes have layer structures, the (essentially planar) layers being
      constructed from rings of six TMA molecules, hydrogen bonded through four
      'carboxyl dimers' and two 'interrupted dimers', where methanol (ethanol) is
      included in the R4(4)(12) (graph set) ring. The packing of the layers differs in
      the two complexes, leading to different three-dimensional structures. In the
      methanol complex, one pyrene molecule is located within the layer and the other,
      at a centre of symmetry, between the layers in one type of interlayer space,
      while the methyls of methanol protrude into the other type of interlayer space.
      In the ethanol complex, the superpositioning of the layers is such that two types
      of stack are formed; one of these is mixed, containing pyrene and one of the
      independent TMA molecules in alternating sequence, while the other stack contains
      only the second type of TMA. Spectroscopic study is needed to establish whether
      the partial mixed stack arrangement in the crystalline ethanol complex implies
      donor-acceptor interaction.

PMID- 11574726
TI  - Polymorphism of maleic hydrazide. I.
AB  - The third polymorph (denoted MH3) of maleic hydrazide (3,6-dihydroxypyridazine in
      the monolactim form, 6-hydroxy-3-pyridazinone, C4H4N2O2) has been studied by X
      ray diffraction and shown to be monoclinic, space group P2(1)/n. Polymorph MH3
      was found as the prevailing form along with the rare triclinic polymorph MH1,
      space group P1;, but they were obtained separately from monoclinic MH2, space
      group P2(1)/c. The structure of MH1, previously studied by photographic methods,
      has been redetermined. Polymorph MH3 exhibits the same scheme of molecular
      association into hydrogen-bonded ribbons as in MH1 and MH2, but the arrangements
      of the aggregates and details of their supramolecular conformations are
      different. The accommodation of the supramolecular conformations to the
      requirements of close packing of the aggregates in crystal lattices, as well as
      the symmetries of the polymorphs, are analyzed.

PMID- 11574727
TI  - Self-association and stereochemistry study of 2-methylthio-, 2
      dimethylaminocyclohexanone oximes and the parent cyclohexanone oxime.
AB  - X-ray diffraction analyses of 2-substituted cyclohexanone oximes C5H9(X)C=NOH [X
      = SMe (1), NMe2 (2)] and of the parent compound [X = H (3)] showed that their
      cyclohexyl rings are in a slightly distorted chair conformation. These compounds
      assume in the solid state the (E) configuration bearing the 2-substituents in the
      axial conformation. Compounds (1) and (2) exist as dimeric and polymeric hydrogen
      bond associates, respectively. Low-temperature X-ray analysis of the
      cyclohexanone oxime (3) showed that the molecules are associated forming two
      independent trimers. The dimer in (1) and the trimer in (3) are built up via [O
      H...N=C] hydrogen bonds, while the polymer of (2) is via the [OH...NMe2] hydrogen
      bond. The comparative IR nu(OH) and nu(C=N) analysis of the title compounds, in
      the solid state and in CCl4 solution, fully supports the nature of the associates
      for (1)-(3) obtained by X-ray diffraction. The IR azomethyne frequency shift
      analysis (Deltanu(C=N)) also suggests the occurrence of the pi(C=N)/sigma*(C-X)
      orbital interaction which stabilizes the axial conformations of (1) and (2).

PMID- 11574728
TI  - Studies of molecular structure parameters of 20-piperidin-2-yl-5alpha-pregnan
      3beta,20-diol and its N-methyl derivative: two inhibitors of Delta24(25) sterol
      methyl transferase and Delta24(24') sterol methyl reductase of Trypanosoma cruzi.
AB  - Molecular structural parameters of two potential drugs against Trypanosoma cruzi
      epimastigotes, 20-piperidin-2-yl-5alpha-pregnan-3beta,20-diol (1) and 20-N
      methylpiperidin-2-yl-5alpha-pregnan-3beta, 20-diol (2) were studied using a
      combination of a stereoselective synthetic route, spectroscopic characterization
      and single-crystal X-ray analysis. Both compounds were synthesized with an R
      configuration at C20. This chirality is a consequence of the stereoselectivity
      observed during the formation of the intermediate 20-pyridin-2-yl-5alpha-pregnan
      3beta,20R-diol (4). NMR data indicated that the six-membered aza ring of (2) is
      conformationally more restrained, in CDCl3 solution, than (1). X-ray studies
      showed that maximum deviations among structural molecular parameters of (1) and
      (2) correspond to torsion angles along the C20-C22 bonds, leading to a different
      relative orientation of the N atom; a critical structural parameter for the
      binding properties of aza-sterols to Delta(24(25)) sterol methyl transferase.
      Cremer-Pople parameters of the five-membered rings of (1) and (2) lie in the
      observed range for a family of tetracyclic fused ring systems retrieved from the
      CSD. The phi2 parameter of (1) lies just on the mean of the family, while phi2 of
      (2) deviates significantly towards the lower limit.

PMID- 11574729
TI  - Space-group changes: a revision to a revision.
AB  - The space group for the entry under the reference codes FEBMUU and FEBMUU01 in
      the Cambridge Structural Database (1992) should be further corrected to space
      group C2/c rather than P1 (FEBMUU) or C2 (FEBMUU01).

PMID- 11574730
TI  - Does nanotechnology apply to dialysis?

PMID- 11574731
TI  - Disease management: what have we learned so far?
AB  - Disease management (DM) is becoming an increasingly important tool for use in end
      stage renal disease (ESRD). The goal of a DM program is to offer a continuum of
      care that uses guidelines and case management protocols to prevent acute care
      episodes, achieve improved outcomes and reduce health care costs. This article
      reviews the theory behind DM, describes key components of DM programs and
      explains the financial incentives for DM in ESRD. Of key importance in the
      increasing role of DM for ESRD has been the development of nationally recognized
      guidelines, the effects of which are now beginning to emerge. At the same time,
      recent studies have identified targeted opportunities for DM programs to improve
      outcomes and costs, including anemia management, dialysis dose, and vascular
      access. DM, through the use of guidelines and targeted toward these and other
      areas, has the potential to significantly impact the quality of care provided to
      ESRD patients.

PMID- 11574732
TI  - Newly developed immobilized polymyxin B fibers improve the survival of patients
      with sepsis.
AB  - BACKGROUND: Sepsis and septic shock are still major causes of morbidity and
      mortality in spite of the availability of powerful and broadly active
      antibiotics. METHODS: A prospective, open and randomized trial of the effect of
      immobilized polymyxin fibers (PMX-F) on the survival of patients with sepsis
      throughout a follow-up period of 28 days or until discharge, if earlier, was
      carried out. Ninety-eight patients were included who met at least 4 of the
      criteria for systemic inflammatory response syndrome due to infection. The
      patients were classified into three groups based on their Acute Physiology and
      Chronic Health Evaluation (APACHE) II score. RESULTS: The overall survival rate
      was significantly improved by using PMX-F compared to the control group (41 vs.
      11%) (p = 0.002). In patients with an APACHE II score less than 20, treatment
      with PMX-F was shown to improve outcome (65 vs. 19%) (p = 0.01). In cases of more
      severe sepsis with an APACHE II score of 20-29, PMX-F still maintained efficacy
      in improving outcome (40 vs. 11%) (p = 0.04). However, PMX-F treatment did not
      improve the survival rate in patients with an APACHE II score of greater than 30
      (survival rate 7 vs. 0%) (p = 0.59). CONCLUSION: From these results, it is
      concluded that treatment with PMX-F in patients with sepsis is effective and
      prolongs the survival rate when applied at an early stage of sepsis. However, in
      severe sepsis, this therapy does not improve the survival rate.

PMID- 11574733
TI  - Biocompatibility of hemodialysis membranes: interrelations between plasma
      complement and cytokine levels.
AB  - Hemodialysis (HD) membrane biocompatibility is defined as absence of complement
      activation. We have recently shown that circulating levels of interleukin (IL) 1
      and IL-2 predict death and survival, respectively, of HD patients. Studies have
      assessed IL-1 in treatments with biocompatible and less biocompatible dialysis
      membranes, but no study has correlated circulating levels of all these
      immunoreactants. We assessed these immunoreactants, and temperature as an
      outcome, during HD in patients treated with different membranes. Twelve stable
      patients, receiving thrice-weekly chronic bicarbonate HD, were randomly dialyzed
      with three different types of membranes, composed of: Cuprophan, cuprammonium
      rayon modified cellulose, and Hemophan. Blood was drawn from the arterial line
      port before (Pre) and 15, 30, and 60 min during and after (Post) HD. Patients'
      temperatures were measured before and after each treatment. The plasma
      concentrations of IL-1 and IL-2 and factors C3a and C5a were assessed by ELISA.
      There were no differences between baseline levels of any of the immunoreactants
      in patients treated with different dialyzers. C3a, C5a, and IL-1 levels increased
      significantly during HD treatments with all three different membranes. C3a, C5a,
      and IL-1 levels during Cuprophan and Hemophan treatments were significantly
      higher than the levels during modified cellulose treatment at 30 and 60 min and
      Post (p < 0.01). For all the immunoreactants, however, the Post levels were
      higher than the Pre levels. In contrast to IL-1, there were no differences in
      mean IL-2 levels during treatments when different membranes were compared. There
      were few correlations of plasma C3a and C5a levels with plasma IL-1 levels, but
      there was only one treatment time in one dialyzer group during which IL-2 and any
      of the other factors were correlated. Pre and Post temperature values and percent
      change in temperature were not correlated with any of the immunoreactants
      measured. These data show that C3a, C5a, and IL-1 responses are similar, but not
      identical, during treatments with different membranes. The response of
      circulating IL-2 levels to treatments is quite different from that of plasma C3a,
      C5a and IL-1 levels and suggests that these changes are not solely due to
      treatment factors. Treatment with modified cellulose membranes is associated with
      a different immunoreactive profile as compared with patients dialyzed using other
      cellulose membranes. We suggest that circulating IL-1 levels are good
      biocompatibility markers.

PMID- 11574734
TI  - Blood components influence cytokine induction by bacterial substances.
AB  - While some studies clearly demonstrated transfer of cytokine-inducing substances
      (CIS) through dialysis membranes, other authors were unable to reproduce such a
      transfer. This inconsistency may have been caused by marked differences in
      experimental design. We performed a systematic evaluation of cytokine induction
      in whole blood and from separated peripheral blood mononuclear cells (PBMC) using
      either purified lipopolysaccharide (LPS) or culture supernatants from various
      bacterial strains. An in vitro hemodialysis circuit with whole blood in the blood
      compartment was employed; the dialysate was contaminated with sterile filtrates
      from Pseudomonas aeruginosa cultures. Addition of plasma samples from the blood
      side to PBMC readily induced interleukin (IL)-1beta and IL-6 after contamination
      of the dialysate, while the same samples failed to induce cytokine production in
      whole blood. In experiments using direct incubation, purified P. aeruginosa LPS
      induced more IL-1beta and IL-6 in whole blood compared to PBMC. In contrast,
      bacterial filtrates from Escherichia coli, Enterobacter cloacae and especially P.
      aeruginosa induced significantly less cytokines in whole blood compared to PBMC.
      Addition of erythrocytes but not granulocytes decreased cytokine induction by
      bacterial filtrates as well as by LPS, probably by adsorption of these
      substances. The addition of 30% plasma increased cytokine induction by LPS but
      decreased cytokine induction by P. aeruginosas filtrates. Our results suggest
      that cellular and plasmatic components of whole blood interact with bacterial CIS
      altering their pyrogenic activity. The detection of CIS depends on the test
      system used; whole blood cultures are not as sensitive for the detection of CIS
      from bacterial filtrates as PBMC cultures.

PMID- 11574735
TI  - Analysis of beta(2)-microglobulin kinetics in hemodialysis by a modified variable
      volume one-compartment model.
AB  - It has been reported that deposition of beta(2)-microglobulin (BMG) is associated
      with the occurrence of dialysis-related amyloidosis (DRA) in long-term
      hemodialysis (HD) patients. Though reduction of the BMG burden is essential in
      preventing DRA, simple BMG kinetic models applicable to clinical practice have
      not been established. We have reported a modified variable-volume one-compartment
      model (1CM) for analyzing urea nitrogen (UN) kinetics, in which no specific
      parameters other than a modification factor are necessary. If there is a constant
      relation between the BMG concentration of the dialyzer arterial line and the mean
      BMG concentration in the body during HD, the modified 1CM may also be applied to
      BMG. As such, in order to verify its validity, we analyzed UN and BMG kinetics by
      the modified 1CM in 28 HD patients in whom polysulfone dialyzers were used, and
      compared the calculated and measured solute rebound. In 3 of the patients, the
      spent dialysate was collected in a tank, and the BMG removal mass, calculated by
      the modified 1CM, was compared with that recovered in the tank. The BMG rebound
      ratio (%), calculated by the modified 1CM, was not different from the measured
      one (36.3 +/- 9.9 vs. 36.5 +/- 11.5, p = 0.954), as in the case of UN (15.8 +/-
      4.5 vs. 16.3 +/- 4.6, p = 0.541). The solute dilution in the blood circuit by
      solute disequilibrium and blood recirculations for BMG was estimated to be 74%
      stronger than that for UN. The normalized solute generation rate (mg/min/l) and
      the time-averaged solute concentration over a 1-week period (mg/l) were 0.142 +/-
      0.023 and 448 +/- 68 for UN and 0.00578 +/- 0.00125 and 22.4 +/- 4.6 for BMG,
      respectively. The differences between these two solutes resulted in a Dilution
      index for BMG that was 23% lower than that for UN (2.62 +/- 0.44 vs. 3.21 +/-
      0.39, p < 0.0001). The modified 1CM overestimated the BMG removal mass (mg) by
      about 20% compared with that recovered in the tank (195 +/- 22 vs. 162 +/- 17, p
      < 0.0001). One of the causes of this discrepancy was speculated to be adsorption
      of BMG by polysulfone dialyzers. It was concluded that, despite several problems
      in quantitative analysis, the modified 1CM would be a useful model for estimating
      the dialysis efficiency for BMG removal in clinical practice.

PMID- 11574736
TI  - Changes in heart rate variability in chronic uremic patients during
      ultrafiltration and hemodialysis.
AB  - BACKGROUND: The analysis of heart rate variability (HRV) is a useful tool to
      evaluate cardiac autonomic modulation, which is frequently impaired in chronic
      uremia. AIMS: The aim of this study was to evaluate HRV in chronic uremics and to
      separately investigate the acute changes induced by volume depletion and solute
      removal during a hemodialysis session. METHODS: Fourteen uremic patients (8 males
      and 6 females, aged 50 +/- 15 years) on maintenance hemodialysis and 14 sex- and
      age-matched healthy controls were studied. Both groups underwent ambulatory
      electrocardiogram monitoring to evaluate the HRV time and frequency domain
      indices. The hemodialysis session was performed by 1 h of high-rate isolated
      ultrafiltration followed by 3 h of bicarbonate diffusive procedure. RESULTS: In
      uremic patients, the overall variability in the frequency [low-frequency power
      (LF): 505 +/- 473, vs. 1,446 +/- 654; high-frequency power (HF): 133 +/- 162 vs.
      512 +/- 417; p < 0.001] and time domain indices (standard deviation of normal R-R
      intervals: 101.9 +/- 33.3 vs. 181.7 +/- 44.1 ms; p < 0.001) was markedly reduced
      compared to controls, whereas mean heart rate (83 +/- 12.4 vs. 60.9 +/- 8.8 bpm;
      p < 0.001) and LF/HF ratio (5.8 +/- 3.5 vs. 2.2 +/- 0.8; p < 0.001) were
      increased. Isolated ultrafiltration produced a marked further decrease in HRV
      indices, but the subsequent diffusive hemodialysis procedure, with a low
      ultrafiltration rate, made HRV increase again. CONCLUSIONS: Chronic uremics
      showed abnormal autonomic modulation with sympathetic-vagal imbalance. The
      unbalanced hypersympathetic response to body fluid depletion is related to the
      ultrafiltration rate. Low interdialytic weight gain and a low ultrafiltration
      rate, associated with adequate hemodialysis, should be the preferable strategy
      for uremic patients with autonomic dysfunction.

PMID- 11574737
TI  - Long-term outcome of permanent hemodialysis catheters: a controlled study.
AB  - AIMS: Hemodialysis tunneled catheters are widely used nowadays. However, their
      complications, infection and dysfunction, remain much too frequent. Different
      types of tunneled silicone hemodialysis catheters are available. We prospectively
      compared the long-term outcome of the two most popular devices, Permcath cuffed
      double catheter and TwinCath uncuffed twin catheter, both inserted
      percutaneously. METHODS: From January 1994 to April 1998, 125 tunneled catheters
      were inserted in the internal jugular vein of 86 chronic hemodialysis patients,
      63 TwinCath MedComp (TC) and 62 Permcath Quinton (PC). They were prospectively
      followed looking for technical patency, infection and dysfunction rate. RESULTS:
      TC were used more often for iterative access (52 vs. 25%, p = 0.01) and were
      inserted more frequently in the left internal jugular vein (59 vs. 16% p <
      0.001). Their median technical survival rate was longer (869 vs. 433 days for PC,
      p < 0.01) with a 1-year patency rate of 80 vs. 53% (p = 0.002). Total catheter
      extrusion was also slightly less frequent with TC (4.7 vs. 9.6%), but partial
      extrusion happened more frequently (43 vs. 16%, p = 0.02). No significant
      difference in infection rate was observed, 0.77 for TC vs. 1.3 local
      infection/1,000 catheter days; 1.08 vs. 1.30 bacteremia/1,000 catheter days. A
      persistent catheter thrombosis was observed in 7.9 vs. 20.9% in PC (p = 0.04),
      the number of dysfunction was 10.5 vs. 24/1,000 days in use (p = 0.0001) and the
      number of urokinase infusion was 4.4 vs. 12/1,000 days (p = 0.001). PC needed
      more radiological interventions for dysfunction with endolumenal brushes (4 vs.
      0) or fibrin sleeve removal (4 vs. 0). The vena cava thrombosis incidence was not
      different (2 vs. 3). CONCLUSION: Although the study was not randomized, TC
      appears more efficient allowing for a longer patency with a lower dysfunction
      rate than PC. This was reinforced by less favorable conditions of TC including
      more left jugular side and more iterative catheters. The cuff does not offer a
      better bacteriological barrier or protection against extrusion, and the TC seems
      at a less risk of fibrin sleeves. However, a large randomized study is needed to
      definitively conclude.

PMID- 11574738
TI  - The influence of hypoalbuminemia on maximal flow rates and transmembrane pressure
      during plasmapheresis--an in vitro study.
AB  - BACKGROUND: Plasmapheresis has been used for the treatment of acute liver failure
      (ALF). In these patients, hypoalbuminemia is often observed. Since albumin
      improves the disaggregability of erythrocytes, hypoalbuminemia might deteriorate
      rheology and thus influence the overall performance of plasmapheresis. METHODS:
      Hypoalbuminemia was mimicked by using porcine blood because of its
      physiologically low albumin/globulin ratio (AGR). Filters (n = 16) were
      integrated in a closed extracorporeal in vitro system. In the control group (n =
      8), native porcine blood (AGR 0.8) was used. In the study group (n = 8), we used
      porcine blood supplemented with human albumin to obtain the human AGR value of
      1.2. Two different heparinization protocols were compared in each group (2.5
      IU/ml: n = 4 with albumin and n = 4 without albumin versus 5 IU/ml: n = 4 with
      and n = 4 without albumin). RESULTS: In both heparinization protocols the higher
      AGR led to lower transmembrane pressure (TMP) levels compared to the lower AGR.
      The reduced TMPs enabled higher blood flow and filtration rates. CONCLUSION:
      Maintenance of a physiological AGR in ALF patients might improve the performance
      of plasmapheresis and--as opposed to raised heparinization--contribute to a safer
      application.

PMID- 11574740
TI  - A comparison of selected antihypertensives and the use of conventional vs
      ambulatory blood pressure in the detection and treatment of hypertension.
AB  - This multicenter, randomized, double-blind, parallel group study was undertaken
      to determine the effectiveness of selected antihypertensives (doxazosin,
      amlodipine, enalapril, and bendrofluazide) in maintaining 24-hour control of
      blood pressure (BP). The predictive value of ambulatory (A)BP versus clinic (C)BP
      measurements as a method for detecting patients with hypertension was also
      evaluated. A total of 204 patients were screened and of these 110 were diagnosed
      as mild to moderately hypertensive with clinic diastolic BP 100-110 mm Hg (> or
      =95 mm Hg in patients with coronary heart disease risk factors). The 4
      antihypertensives were all equally effective at controlling BP over 24 h, as
      shown by 24-hour ABP measurements. The incidence of adverse events was similar
      for all 4 treatment groups; headache was the most common event, being reported by
      22 patients (20%). There was a clinically relevant reduction in total cholesterol
      for the doxazosin (-15.4 mg/dl) and amlodipine (-11.6 mg/dl) treatment groups in
      comparison with enalapril and bendrofluazide. Our results from ABP measurements
      suggest that the antihypertensives studied are effective first-line therapy in
      the regulation of hypertension and that ABP is a reproducible measure. ABP may
      also be useful in identifying patients with various types of high BP, for
      instance those with 'white coat' hypertension, enabling more accurate screening
      and diagnosis.

PMID- 11574741
TI  - Amlodipine: effective for treatment of mild to moderate essential hypertension
      and left ventricular hypertrophy.
AB  - This was a 20-week, open-label, uncontrolled clinical investigation of the long
      acting calcium antagonist amlodipine in 33 male or female patients with essential
      hypertension and left ventricular hypertrophy (LVH). A once-daily dose (5-10
      mg/day) of amlodipine provided a consistent antihypertensive effect, reducing the
      sitting diastolic (-13.8% change) and systolic (-13.0% change) blood pressures by
      clinically meaningful and statistically significant (p = 0.0001, n = 33) amounts.
      Amlodipine had no effect on heart rate. A significant regression in LVH was seen
      (left ventricular mass index reduced from 169.0 [SD 30.7] g/m(2) to 140.6 [SD
      19.6] g/m(2), p < 0.01, n = 12). There was also a significant reduction in total
      peripheral resistance and improvement in left ventricular diastolic filling (E/A
      ratio increased from 0.86 pre-treatment to 1.03 post-treatment, p = 0.038, n =
      12). These results are consistent with other studies in showing that a relatively
      short treatment regimen with amlodipine is associated with a significant
      reduction in left ventricular mass index.

PMID- 11574742
TI  - Is postural hypotension a real problem with antihypertensive medication?
AB  - Historically, postural hypotension has been cited as a consideration which might
      influence the selection of antihypertensive therapy. The common symptoms
      (dizziness, blackouts, syncope) give cause for concern but they are not
      attributed to every class of antihypertensive drug. For example, administration
      of a beta-blocker is not generally associated with symptomatic postural
      hypotension, whereas the alpha-blocker prazosin was particularly problematical,
      with a significant and well-recognized risk of first-dose postural effects.
      Titration from a low starting dose and careful selection/monitoring of patients
      have been successfully used to circumvent this problem. However, since there is a
      relatively high incidence of postural hypotensive symptoms in elderly patients in
      general, it may be a misconception to attribute such symptoms to any particular
      type of antihypertensive drug. Furthermore, with the newer alpha(1)-blockers,
      such as doxazosin, which have a more gradual onset of action, there is a markedly
      reduced tendency for postural hypotension to occur. Thus, it is perhaps time to
      reassess the real significance of iatrogenic postural hypotension in the
      selection of antihypertensive therapy.

PMID- 11574743
TI  - [Physical exercise, nutrition and sunshine exposure for the prevention of
      osteoporosis].
AB  - BACKGROUND: Social and economic impact of osteoporosis is growing. Prevention
      deserves more attention than at present. Since previous reviews on prevention of
      osteoporosis by the author, many original papers and reviews on the subject have
      been published. Which interventions are effective? METHODS: A MEDLINE search was
      performed using the search terms 'osteoporosis' and 'calcium' or 'vitamin D' or
      'ultraviolet' or 'sunshine' or 'nutrition' or 'exercise' or 'hormone'.
      Additionally, references of recent publications were searched for significant
      contributions. Relevant publications as assessed by the author were included into
      the present review. RESULTS AND CONCLUSIONS: Regular high-impact physical
      exercise, a daily allowance of at least 1000 mg calcium, a sufficient
      supplementation with vitamin D through UVB-exposure of the skin or oral
      supplementation, and hormonal replacement therapy in deficiency states are the
      fundamentals of prevention of osteoporosis.

PMID- 11574744
TI  - Antiviral action of Euphorbium compositum and its components.
AB  - INTRODUCTION: Euphorbium compositum SN (Biologische Heilmittel Heel GmbH, Baden
      Baden, Germany, a homeopathic combination preparation available in form of drops,
      nasal spray, and injection solution), is prescribed for inflammation of the
      mucosae of the nose and sinuses. Infections in these areas are primarily of viral
      origin although bacterial superinfections are also common. OBJECTIVE: The main
      question was whether or not this homeopathic remedy shows an activity against
      viruses responsible for infections of the respiratory tract. METHODS: This in
      vitro study using virus plaque reduction assays examined the effect of Euphorbium
      compositum SN against pathogens causing various viral infections: influenza A
      virus, respiratory syncytial virus (RSV), human rhinovirus (HRV) and herpes
      simplex virus type 1 (HSV-1). RESULTS: Analysis of virus production after
      treatment of the infected cells with the remedy showed an antiviral activity of
      Euphorbium compositum SN against RSV and HSV-1. In addition, an antiviral effect
      against influenza A virus and HRV, though minimal, was, also noted. Analyses of
      the plant-derived components of Euphorbium compositum SN, e.g. Euphorbium
      resinifera, Pulsatilla pratensis and Luffa operculata for their antiviral
      activity revealed a clear activity of Euphorbium resinifera and Pulsatilla
      pratensis against RSV. In contrast, no effect was detected using the same
      protocol with Luffa operculata. CONCLUSIONS: Euphorbium resinifera and Pulsatilla
      pratensis as components of Euphorbium compositum SN are responsible for its
      antiviral activity.

PMID- 11574745
TI  - [Can homeopathy be integrated in a university hospital?].
AB  - BACKGROUND AND OBJECTIVE: The Dr. von Hauner Children's Hospital Munich has
      conducted a pilot project for 4 years, aiming at the integration of homeopathic
      concomitant treatment into daily clinical practice. This study was carried out to
      clarify whether the project is successful and accepted by physicians, nurses, and
      parents. METHODS: Questionnaires, all standardized and anonymous, were handed out
      to 137 physicians, 212 nurses and paramedics, and 1,048 parents of children
      treated at the hospital. RESULTS: 69% of the physicians appreciated concomitant
      homeopathic treatments, more than 60% believed the integration of homeopathy is
      suggestive, 75% saw a need for clinical research in homeopathy. 25% of the staff
      now had a more positive view towards homeopathy. 63% of the parents appreciated
      concomitant treatment, but only 19% are willing to participate in double-blind
      studies. CONCLUSIONS: Integration of homeopathy in a university hospital is
      possible. Therapeutic work should be accompanied by scientific research.

PMID- 11574746
TI  - [Quality of outcome in treating patients with chronic headache within a hospital
      specialized for migraine. A cohort study with one-year follow-up].
AB  - AIMS: To describe characteristics of in-patients with chronic headache syndromes
      being treated with complementary methods, short-term effects at time of discharge
      as well as long-term effects covering a catamnesis of 1 year. METHODS: The study
      was designed as a prospective cohort study with outcome measurements 2 months in
      advance of admission to the hospital, at admission, and at time of discharge,
      continued by follow-up queries 2, 6 and 12 months after discharge from the
      hospital. The parameters for describing the course of headache symptoms were
      registered by questionnaires and diaries. During the first 6 months in 1996, a
      total of 424 consecutive patients with migraine or tension-type headache at the
      'Migrane-Klinik Konigstein' were included. RESULTS: 82.9% of the patients were
      women, the mean age was 46.3 +/-13.0 years. The median of the duration of the
      disease was 23 years. At discharge from the hospital there was a marked
      improvement regarding frequency of headache attacks, intensity of headaches, and
      concomitant symptoms. 60.5% of the patients were classified as 'responders'.
      67.5% responded to follow-up questionnaires. With exception of the duration of
      headache attacks, a significant improvement regarding the 6-month follow- up
      compared to base level was observed. Intake of drugs could be diminished and
      quality of life was improved. Patients suffering from tension-type headache
      showed smaller effects in general. CONCLUSIONS: Taking into account the mean
      duration of disease of more than 20 years the results suggest a clinically
      relevant success from the patients' view regarding the short-term as well as the
      long-term course. The problem of data loss with follow-up queries and missing
      comparative data reduce the conclusiveness of the results.

PMID- 11574747
TI  - [Clinical remission of an HLA B27-positive sacroiliitis on vegan diet].
AB  - BACKGROUND: Positive effects of fasting and vegan diet in patients with rheumatic
      diseases are reported in the literature. MEDICAL HISTORY: We present a 33-year
      old patient with double-sided HLA B27-positive sacroiliitis, which was diagnosed
      by magnetic resonance tomography. Since about 10 years he therefore had pain in
      the iliosacral region. Numerous sessions of physiotherapy, a cure treatment, and
      treatment with sulfasalazine and doxycycline were not effective. The patient was
      dependent on the daily intake of the nonsteroidal antirheumatics meloxicam 2 x
      7.5 mg and ibuprofen 400-800 mg and the analgetic tramadol 50-150 mg, but evening
      and night pain and morning stiffness persisted under this treatment. TREATMENT:
      We recommended a temporary vegan diet, i.e. to completely avoid animal fats and
      proteins. COURSE: 3-4 days after changing on vegan diet the complaints improved
      distinctly and persistently. After consumption of meat 6 weeks later, complaints
      worsened. Consequent vegan diet again resulted in significant improvement of the
      pain and morning stiffness. At follow-up 3 months after the initial contact,
      tramadol and ibuprofen intakes had been stopped, meloxicam had been reduced to 1
      x 7.5 mg. The patient was almost completely free of complaints. CONCLUSIONS: It
      was demonstrated that in a single case of sacroiliitis which was refractory to
      other treatment, vegan diet resulted in a convincingly improvement of complaints.

PMID- 11574748
TI  - Chemoattractant receptors expressed on type 2 T cells and their role in disease.
AB  - The existence of two functionally distinguished populations among T cells has
      been established in both mice and humans. Type 1 T helper (Th1) cells are
      involved in the defense against intracellular bacteria and many viruses, while
      type 2 Th cells (Th2) are the major actors in the response against parasites and
      play a central role in allergic inflammation. More recently, several data have
      suggested that some chemokine receptors are tightly regulated on T cells, and in
      accordance with this selective expression, Th1 and Th2 cells can be
      differentially recruited by specific chemokines to the inflammatory sites. Among
      Th2-associated chemokine receptors, CCR3, CCR4 and CCR8 have been described to
      play a central role in allergic inflammation. However, CCR3 is mainly expressed
      on basophils, eosinophils and mast cells, but it is poorly expressed by Th2
      cells, and CCR4 is also expressed by Th subsets different from Th2 cells. So far,
      the chemoattractant receptors which among T cells appear to be selectively
      expressed by Th2 cells or their subsets are CCR8 and CRTH2. The ligand for CRTH2
      is not a chemokine, but is prostaglandin (PG)D2, which is able to attract
      basophils, eosinophils, Th2 cells and type 2 cytotoxic (Tc2) CD8+ T lymphocytes.
      The selective expression of CRTH2 on Th2 and Tc2 cells may be useful to develop
      new therapeutic strategies against allergic diseases and against other immune
      disorders. Additional studies, however, are required to understand its effective
      importance in the induction and maintenance of Th2- or Tc2-mediated response and
      inflammation.

PMID- 11574749
TI  - Cupressaceae pollinosis: identification, purification and cloning of relevant
      allergens.
AB  - Allergy to Cupressaceae pollen is a worldwide pollinosis caused by several
      species. Pollen extracts prepared from allergenic species belonging to this
      family are characterised by low protein and high carbohydrate content. The
      allergenic components represented in the pollen extracts from different species
      of the Cupressaceae family show high levels of cross-reactivity when probed with
      human IgE from allergic subjects and share a number of common epitopes also
      identified by polyclonal rabbit antisera and monoclonal antibodies. A close
      relationship has also been described with the Taxodiaceae and Podocarpaceae
      families. Although both proteic and carbohydrate epitopes appear to be involved
      in IgE recognition and allergenic cross-reactivity, a large portion of the IgE
      reactivity of Cupressaceae-allergic patients seems to be associated with sugar
      moieties present on the relevant allergenic molecules. From this point of view,
      Cupressaceae/Taxodiaceae allergens constitute a particularly useful model to
      study IgE cross-reactivity, as they have been shown to display different levels
      of homology. Moreover, the availability of the purified allergens, together with
      their recombinant counterparts, may shed light on the actual role played by
      carbohydrate in allergic sensitisation, IgE recognition and allergenic cross
      reactivity.

PMID- 11574750
TI  - The role of eosinophils in asthma: Sarastro or the Queen of the Night?
AB  - Eosinophils used to be thought of as regulators of allergic inflammation, but
      there is now evidence to the contrary; eosinophils have been found to be the
      major effector cells responsible for the late asthmatic response (LAR), airway
      hyperresponsiveness (AHR) and, at least in part, airway remodeling by releasing
      leukotrienes and highly basic and cytotoxic proteins such as major basic protein
      (MBP). However, a recent clinical trial using humanized anti-interleukin-5
      monoclonal antibody found a failure to reduce AHR and the LAR, whereas the
      antibody entirely abolished tissue eosinophilia. In addition, abundant MBP has
      recently been found in mast cells as well as in eosinophils by our transcriptome
      (the whole transcripts that a cell expresses) screening of all leukocyte types.
      Eosinophils are indeed unlikely to be involved in the LAR and may not be unique
      cytotoxic cells in asthma. It is now necessary to determine the real role of
      eosinophils and whether early intervention to block eosinophil recruitment into
      the asthmatic lung does prevent airway remodeling and AHR.

PMID- 11574751
TI  - Allergy to dermatophagoides in a group of Spanish gypsies: genetic restrictions.
AB  - BACKGROUND: Spanish gypsies have traditionally lived as nomads, a reason why few
      epidemiological studies were done in this ethnic group. However, the high
      prevalence of asthmatic diseases demonstrated in a population residing in the
      North of Spain induces us to analyse whether it was due to the influence of
      genetic loci previously implicated in other population studies as causing the
      disorders. METHODS: DRB1* and DQB1* HLA class II, TCR-Valpha8.1, FcepsilonRI-beta
      Rsa I exon 7 and intron 2, TNF-beta (LTalpha-Nco I) and CD14, were tested for
      association with asthma and atopy by multiple regression analysis, in 5 families
      comprising 87 individuals. RESULTS: Significant associations were found with
      DQB1*02 (p = 0.02) and DQB1*0301 (p = 0.008) and elevated levels of total serum
      IgE. A negative association (p = 0.02) was found between total serum IgE and
      DRB1*14. FcepsilonRI-beta Rsa I-In2 allele 1 was associated with high levels of
      total serum IgE (p = 0.04). Levels of Der p 1 IgE antibodies were negatively
      associated with DRB1*11-DQB1*0301 (p = 0.007), and positively with TCR Valpha-8
      allele 1 (p = 0.04) and with FcepsilonRI-beta Rsa I-In2 allele 1 (p = 0.009).
      CONCLUSIONS: Our results do not show any association between asthma and the
      genetic loci studied although they do suggest the existence of multiple genetic
      influences on the allergic response in these families.

PMID- 11574752
TI  - Suppression of specific and bystander IgE responses in a mouse model of oral
      sensitization to beta-lactoglobulin.
AB  - BACKGROUND: Mechanisms of systemic IgE suppression by oral tolerance have been
      extensively studied, but less is known about oral tolerance induction in mice
      challenged at mucosal sites. We have previously shown in systemically challenged
      mice that high-dose tolerance suppressed specific but not bystander IgE. In an
      attempt to mimic oral tolerance in food-allergic patients, we have investigated
      how IgE suppression could be induced in mice sensitized orally against beta
      lactoglobulin (BLG). METHODS: Mice were immunized orally against BLG using
      cholera toxin as adjuvant. Before oral sensitization, mice were administered milk
      whey proteins, either in the form of a single high-dose gavage, or by prolonged
      ad libitum administration of various doses. RESULTS: Orally sensitized mice
      mounted a BLG-specific IgE response. In contrast to systemically challenged mice,
      a single high-dose gavage of whey protein given prior to the onset of oral
      sensitization resulted in the suppression of both specific and bystander IgE.
      When mice were fed moderate to low doses of milk whey proteins daily ad libitum
      in the drinking water during 3 weeks prior to oral sensitization, all doses
      effectively suppressed antigen-specific IgE. However, bystander IgE suppression
      was observed only at the lowest doses. When mice were tolerized during 4 days
      instead of 3 weeks, IgE titers remained unchanged. CONCLUSIONS: In orally
      sensitized mice, bystander IgE suppression depended on the dose of tolerogen, but
      also on its mode of administration. Mucosally induced IgE responses were
      suppressed by a mechanism that was distinct from that operating in the periphery.

PMID- 11574753
TI  - Sensitizing capacity and residual allergenicity of hydrolyzed cow's milk
      formulae: results from a murine model.
AB  - BACKGROUND: Cow's milk allergy is the most common cause of clinically relevant
      adverse reactions to food in infants and children. Partially and extensively
      hydrolyzed formulae are used for the therapy and prevention of cow's milk
      allergy. However, the immunogenic potency of hydrolyzed cow's milk formulae to
      induce and/or enhance the allergic phenotype in vivo is still under debate. The
      aim of this study was to assess the sensitizing capacity and residual
      allergenicity of various partially and extensively hydrolyzed cow's milk formulae
      in a murine model of cow's milk allergy. METHODS: BALB/c mice were immunized with
      either a cow's milk formula or various partially and extensively hydrolyzed
      formulae. Immediate cutaneous hypersensitivity reactions and allergen-specific
      antibody production were assessed. RESULTS: Although immunization with cow's milk
      resulted in 12/13 cases in a positive skin test response to intradermal injection
      of cow's milk formulae, only 1 mouse showed a positive skin test to one of the
      partially hydrolyzed formulae, and none showed positive reactions to other
      partially hydrolyzed formulae, any of the extensively hydrolyzed formulae,
      phosphate-buffered saline or the amino acid formula. However, 6 of 8 mice showed
      positive skin tests when immunized with partially hydrolyzed formulae and with
      one of the extensively hydrolyzed formulae. CONCLUSIONS: The residual allergenic
      potential is markedly reduced in many hydrolyzed formulae, but most of the
      formulae investigated could induce an allergic immune response in BALB/c mice.
      Our murine model seems to be suitable to investigate the sensitizing capacity of
      hydrolyzed formulae and to differentiate even between extensively hydrolyzed
      formulae.

PMID- 11574754
TI  - Upon prolonged allergen exposure IL-4 and IL-4Ralpha knockout mice produce
      specific IgE leading to anaphylaxis.
AB  - BACKGROUND: IL-4 and IL-13 are key regulators in atopic disorders and both signal
      through the receptor chain IL-4Ralpha. IL-4 and IL-13 are also the only cytokines
      known to induce class switching to IgE. We sought to compare allergen-specific
      IgE responses and allergic reactivity of wild-type (wt) mice with IL-4-/- and IL
      4Ralpha-/- mice, which lack both IL-4 and IL-13 functions. METHODS: BALB/c wt, IL
      4-/- and IL-4Ralpha-/- mice were immunized with ovalbumin intranasally or
      intraperitoneally and specific antibody titers were measured by ELISA.
      Bronchoalveolar lavage fluids and lung tissue were analyzed cytologically and
      histologically. Allergic reactivity was determined by active cutaneous
      anaphylaxis and anaphylactic shock. RESULTS: wt mice immunized intranasally or
      intraperitoneally showed high titers of specific IgE 3 and 6 weeks after primary
      sensitization, resulting in cutaneous anaphylaxis and anaphylactic shock upon
      challenge. Intranasal sensitization resulted in airway eosinophilia and goblet
      cell metaplasia. In contrast, IL-4-/- and IL-4Ralpha-/- mice showed no specific
      IgE after 3 weeks, but produced high titers after 6 weeks. At this time cutaneous
      anaphylaxis and anaphylactic shock could be induced as in wt mice, but lung
      pathology was absent. CONCLUSIONS: We conclude that upon long-term allergen
      exposure, alternative switch mechanisms independent of IL-4 and IL-4Ralpha may
      induce IgE but not asthma-like lung pathology. This may be relevant for the
      development of allergic disease, since long-term allergen exposure is a frequent
      condition during allergic sensitization.

PMID- 11574755
TI  - Dietary cholesterol enhances pulmonary eosinophilic inflammation in a murine
      model of asthma.
AB  - BACKGROUND: Epidemiological studies have suggested that the dietary pattern may
      be associated with the prevalence of asthma. We previously reported that an
      increased intake of foods of animal origin was associated with the occurrence of
      allergic rhinitis and asthma in adolescents. Here we examined the effect of
      dietary cholesterol in a murine model of allergic pulmonary inflammation.
      METHODS: Weanling C57BL/6 mice were fed a control diet containing 0.02%
      cholesterol or a diet supplemented with 1% or 2% cholesterol. Four weeks later
      the mice were sensitized with intraperitoneal ovalbumin (OVA) followed by OVA or
      saline inhalation 2 weeks later. OVA aerosol-induced inflammation was
      significantly enhanced by dietary supplementation of 1% or 2% cholesterol.
      RESULTS: Among OVA-challenged mice, leukocyte numbers, particularly those of
      eosinophils, in the bronchoalveolar space increased by 3- to 5-fold with the
      cholesterol supplement. Among OVA aerosol-challenged mice, the levels of
      interleukin-5 and cysteinyl leukotrienes in the bronchoalveolar lavage fluid were
      significantly higher in those fed the 2% cholesterol diet compared with mice on
      the control diet. CONCLUSIONS: Dietary cholesterol may enhance pulmonary allergic
      inflammation.

PMID- 11574756
TI  - Theophylline inhibits TNF-alpha-induced CD4 expression on human eosinophils and
      CD4+ eosinophil migration.
AB  - BACKGROUND: Increasing evidence regarding asthma suggests that CD4+ cells are
      preferentially recruited to sites of bronchial inflammation. Interleukin (IL)-16
      has been reported as playing an important role in the accumulation of CD4+ cells.
      We have shown that the CD4 molecule is expressed on normal human eosinophils by
      tumor necrosis factor (TNF)-alpha stimulation. METHODS: We evaluated the effects
      of theophylline, KF19514 [a selective phosphodiesterase (PDE) IV inhibitor] and
      dexamethasone on CD4 expression on eosinophils and eosinophil migration in
      response to IL-16, a natural soluble ligand of the CD4 molecule. RESULTS: The
      maximum eosinophil migration was observed when eosinophils were cultured with TNF
      alpha at 10 ng/ml for 18 h and the concentration of IL-16 was 10 pg/ml. CD4+
      eosinophil migration in response to IL-16 was mostly, if not fully, chemokinetic
      and this migration was significantly inhibited by Fab of anti-CD4 monoclonal
      antibody. Theophylline (10(-4)-10(-3) M), KF19514 (10(-7)-10(-6) M) and
      dexamethasone (10(-8)- 10(-6) M) significantly inhibited CD4 expression on
      eosinophils induced by TNF-alpha. Theophylline (10(-3) M) and KF19514 (10(-6) M)
      inhibited CD4+ eosinophil migratory responses induced by IL-16, but 10(-6) M
      dexamethasone did not. Theophylline and KF19514 augmented the intracellular
      adenosine-3',5'-cyclic monophosphate (cAMP) concentration in eosinophils,
      suggesting modulation by cAMP of CD4 expression and eosinophil migration.
      CONCLUSIONS: These data suggest that TNF-alpha-induced CD4+ eosinophils may
      contribute to eosinophil migratory responses induced by IL-16. Theophylline and
      selective PDE IV inhibitor may prevent airway inflammation by downregulating CD4
      expression on eosinophils and inhibiting eosinophil migration through CD4 and IL
      16 interaction.

PMID- 11574757
TI  - Effect of low-dose cyclosporin a microemulsion on disease severity, interleukin
      6, interleukin-8 and tumor necrosis factor alpha production in severe pediatric
      atopic dermatitis.
AB  - BACKGROUND: The release of cytokines [interleukin-6 (IL-6), IL-8 and tumor
      necrosis factor-alpha (TNF-alpha)] by skin cells is involved in the pathogenesis
      of atopic dermatitis (AD). OBJECTIVE: To evaluate the effect of low-dose
      cyclosporin A (CyA) on clinical symptoms and cytokine secretion in severe
      pediatric AD. METHODS: Ten children with severe AD (SCORAD index >50) were
      treated for 8 weeks with CyA. The initial dose of 2.5 mg/kg/day was titrated to a
      maximum of 5 mg/kg/day until a SCORAD reduction of >or =35% was achieved
      ("treatment response"). After stopping CyA all patients entered a 4-week follow
      up period. Cytokine secretion (IL-6, IL-8 and TNF-alpha) from patients' PBMC was
      assessed by ELISA before and after CyA treatment and was compared with 18 healthy
      nonatopic controls. Only the data of patients, who responded to CyA and did not
      experience a relapse during the follow-up period, were evaluated for this paper.
      RESULTS: Seven patients responded to CyA without relapse during the follow-up
      period. The median SCORAD index in these patients improved from 71 at baseline to
      22 after CyA treatment (p < 0.001). AD patients' PBMC produced more IL-6, IL-8
      and TNF-alpha than PBMC of controls. Suppression of IL-6 (p < 0.05) and IL-8 (p <
      0.05) production was observed after CyA treatment. TNF-alpha levels were
      unchanged by CyA in all patients. CONCLUSIONS: The reduction in severity of
      pediatric AD with CyA is associated with decreased production of IL-6 and IL-8,
      but not TNF-alpha by PBMC.

PMID- 11574758
TI  - Allergic and immunologic parameters in patients with Fanconi's anemia.
AB  - BACKGROUND: Fanconi's anemia (FA) is a rare recessive chromosomal instability
      disorder, characterized by progressive bone marrow failure and congenital
      defects. Patients with FA present with recurrent infections, particularly those
      of the respiratory tract. OBJECTIVE: The aim of the present study was to evaluate
      whether patients with FA have altered antibody-mediated immune responses.
      METHODS: A group of 12 patients with FA, 5-32 years old (6 males) was studied.
      Serum levels of IgG, IgM, IgA and IgG subclasses, isohemagglutinin titers and
      specific IgG antibodies to poliovirus and measles were determined using standard
      methods. Immediate skin tests to common inhalant allergens were performed, and
      total and specific serum IgE was quantitated using a fluoroenzymatic assay (Uni
      CAP, Pharmacia). Antipneumococcal antibodies were measured by ELISA before and 4
      8 weeks after immunization with pneumococcal vaccine (Pneumo 23, Pasteur Merieux
      Connaught). Responses to serotypes 1, 3, 5, 6B, 9V and 14, which are the most
      prevalent in our country, were studied. RESULTS: Ten patients had elevated IgE
      levels in sera, and 7 of them had detectable specific IgE and positive immediate
      skin tests. An inadequate response to pneumococcal vaccination was found in 2 of
      the 12 patients. Isohemagglutinin titers and levels of IgG, IgM, IgA and IgG
      subclasses and antipoliovirus and antimeasles antibodies were within the normal
      limits for age in all patients. Two patients had undetectable IgG4 levels (below
      5 mg/dl). CONCLUSIONS: The results indicate that a proportion of patients with FA
      (2/12) in our study had inadequate responses to pneumococcal vaccination. No
      other significant abnormalities of the immune system were found in these
      patients.

PMID- 11574759
TI  - Impact of chemotherapy on male fertility.
AB  - Testicular tumors and malignant lymphomas are, with increasing incidence, the
      most frequent malignant diseases in men between the age of 15 and 34. With the
      introduction of cisplatin-based polychemotherapy, cure rates rose to over 90% in
      patients with germ cell tumors and were comparably favorable at around 80% in
      those with malignant lymphomas. In view of these high cure rates, increasing
      clinical importance is attached to chemotherapy induced fertility disorders. One
      problem involved in assessing the influence of chemotherapy on fertility is the
      fact that the malignant disease itself strongly alters spermatogenesis. This
      complicates an evaluation of the effect of cytostatic therapy on fertility
      disorders. There are significant cytostatic- and dose-specific differences.
      Longterm infertility due to cytostatic therapy may be expected in more than 50%
      of the patients at a cumulative dose of cisplatin > 0.6 g/m(2), cyclophosphamide
      > 6 g/m(2), and procarbazine >/= 4 g/m(2). However, it takes up to 3 years or
      more for spermatogenesis to recover after the termination of chemotherapy. An
      individual assessment of the post-therapeutic fertility status is extremely
      limited, since variance of the pretherapeutic fertility status causes
      interindividual differences, and the numerical data mentioned above only permit a
      vague estimation. Before patients undergo cytostatic therapy, cryopreservation of
      germ cells should thus be suggested or, in some cases, testicular extraction of
      spermatozoa.

PMID- 11574760
TI  - Treatment of inoperable stage III and IV non-small-cell lung cancer: the
      'average' radiotherapist's point of view.
AB  - Stage III non-small-cell lung cancer (NSCLC) presents a major therapeutic problem
      for the radiation oncologist who treats patients outside of clinical trials. It
      is a heterogeneous disease with great variation of the clinical extent, and the
      optimal therapeutic decision must be based on various parameters: the most
      important unfavorable characteristics are represented by a low Karnofsky
      performance status, weight loss > 5%, locally too advanced disease (e.g. T4,
      positive pleural effusion), intensive symptomatology, and distant metastases. The
      presence of these factors advocates the use of short hypofractionated
      radiotherapy (RT) schemes of one or two fractions (e.g., 1 x 10 Gy, 2 x 8.5 Gy),
      which results in fast and effective palliation. Radical treatment must be given
      to patients without the above-mentioned unfavorable characteristics. Results from
      randomized clinical trials support the use of high RT doses, preferably
      hyperfractionated/ accelerated. The CHART schedule could be used in case of
      squamous-cell histology. Elderly patients could be treated by the standard scheme
      of 30 x 2 Gy (or equivalent). Chemotherapy reduces the risk of (other than brain)
      distant metastases and improves the median survival time, especially for patients
      with non-squamous-cell NSCLC. Platinum-based chemotherapy is usually administered
      in conjunction with RT as inductive and/or concurrent. Patients of stage IV are
      probably candidates for chemotherapy in case of good performance status and for a
      short-term radiotherapy if local symptoms are predominant.

PMID- 11574761
TI  - New developments in the treatment of cervical cancer.
AB  - Cervical cancer is world-wide the second most frequent cancer found in women and
      represents 12% of all female malignancies. In fact, it is the most common female
      cancer in developing countries. There is now sufficient evidence to recommend
      that women with locally advanced cervical cancer confined to the pelvis receive
      concurrent pelvic radiation and chemotherapy. New surgical techniques such as
      laparoscopically assisted radical vaginal hysterectomy and trachelectomy (a
      fertility-preserving radical operation technique) are being established and have
      to be evaluated for their long-term safety. Causal treatment by developing
      multivalent antiviral drugs and vaccines is no longer a pure theoretical
      approach. Despite these improvements, the early diagnosis by colposcopy and
      gynaecological cytology remains the safest method to ensure early treatment
      avoiding death of cervical cancer.

PMID- 11574762
TI  - Targeting protein kinases for tumor therapy.
AB  - Phosphorylation is the most common biochemical modification of cellular
      molecules, regulating fundamental cellular processes like growth,
      differentiation, proliferation, movement, and death. It is now clear that protein
      and lipid kinases as well as phosphatases are causally involved in human disease,
      especially in cancer. The first part of this review tries to compile our current
      knowledge about the involvement of protein kinases in human cancer. Phosphatases
      as well as phospholipid kinases will be omitted from this article for the purpose
      of simplification. In the second part an updated list of ongoing clinical trials
      involving protein kinases as targets for tumor therapy will be given, together
      with a brief summary of technical approaches in targeting protein kinases for
      therapy.

PMID- 11574763
TI  - Mito-flag as salvage therapy for relapsed and refractory acute myeloid leukemia.
AB  - BACKGROUND: This study was performed to examine the feasibility and toxicity of
      the combination of mitoxantrone, fludarabine, cytarabine as bolus (B) or
      continuous infusion (CI) and granulocyte- colony stimulating factor (G-CSF) in
      patients with recurrent and refractory acute myeloid leukemia (AML). PATIENTS AND
      METHODS: 29 patients with relapsed (n =17) or refractory (n =12) AML were treated
      with the Mito-FLAG protocol consisting of mitoxantrone (7 mg/m(2), days 1/3/5),
      fludarabine (15mg/m(2), every 12 h, days 1-5), cytarabine (Ara-C) as bolus
      infusion (1000 mg/m(2) over 1 h, every 12 h, days 1-5) (n =15) or as continuous
      infusion (100-150 mg/m(2) over 24 h, days 1-5) (n =14), and G-CSF (5 mgr;g/
      kg/day, day 0 until a neutrophile count of 0.5 x10(9)/l). RESULTS: 17 patients
      (59%) and 1 patient (3%) achieved complete remission (CR) and partial remission
      (PR), respectively; thus the overall response rate was 62%. Following Mito-FLAG,
      5 patients with CR underwent high-dose therapy (HDT) with allogeneic (n = 2) or
      autologous (n = 3) stem cell transplantation (SCT). With a median follow-up of 28
      (range 6-54) months, 4 transplanted patients are alive in CR (n = 2) or in
      relapse (n = 2). The median duration of event-free survival (EFS) and overall
      survival (OS) was 3.2 and 6.8 months, and probabilities of EFS and OS after 1
      year were 14 and 34%, respectively. The 1-year rates for EFS and OS in this group
      were 18 and 53%, respectively. Median duration of WHO grade 4 granulocytopenia
      and thrombocytopenia was 20 and 23 days, respectively. Nonhematological side
      effects were moderate, predominantly reaching WHO grades 1-2. Neutropenic fever
      was seen in 85% of courses, with a median duration of 4 (1-38) days. Four
      patients (14%) suffered an early death because of aplasia (n = 2), pneumonia (n
      =1) or progressive AML (1 nonresponding patient). CONCLUSIONS: Our data suggest
      that the Mito-FLAG protocol is feasible and can be safely performed with both
      schedules of Ara-C. In this study the regimens have shown high efficacy and
      acceptable toxicity in patients with relapsed or refractory AML. We currently
      examine the importance of bolus versus continuous infusion of Ara-C as part of
      the Mito-FLAG regimen in a prospective randomized multicenter trial.

PMID- 11574764
TI  - Palliation by intratumoral infiltration with natural interferon-beta.
AB  - BACKGROUND: Curative approaches to tumor therapy have achieved greater importance
      through new developments such as cytostatic agents and their combination with
      other therapy concepts, but for the majority of tumor patients only palliative
      therapy is possible. Size or location of tumor manifestations can result in
      severe discomfort for patients, in some cases even in a reduction of
      functionality. PATIENTS AND METHODS: For the purpose of this study, a total of 55
      patients with a variety of advanced malignant diseases nonresponding or
      progressive under radio- and/or chemotherapy were treated by intratumoral
      injection of natural human fibroblast interferon (nIFN-beta). nIFN-beta was
      administered intralesionally 3 times per week for at least 4 weeks at doses of 2
      8 MIU, depending on tumor size. Local tumor response was observed over a median
      follow-up period of 18 weeks. RESULTS: In 37 patients (67%) a complete or partial
      remission of the local tumor manifestation was achieved. Survival times of these
      patients were improved compared with those of patients without local tumor
      remission. 16 patients without significant change of tumor volume benefited from
      the palliative (extensive analgesic) effect of the nIFN-beta therapy. During
      treatment, none of the patients showed a progression of the locally treated
      tumor, even when the basic malignant disease progressed. The side effects of the
      nIFN-beta therapy were tolerable, and no patient discontinued therapy.
      CONCLUSION: From these observations, intralesional nIFN-beta therapy of malignant
      tumors appears to be a useful palliative addition to radio- and/or chemotherapy
      with the aim of local control of tumor growth.

PMID- 11574765
TI  - Inflammatory myofibroblastic tumor with CNS involvement.
AB  - BACKGROUND: Inflammatory myofibroblastic tumors (IMT) represent a spectrum of
      neoplasms that occur in the mesentery and retroperitoneum and less frequently in
      the mediastinum of children and young adults. Transformation into inflammatory
      fibrosarcoma and metastases are rare. CASE REPORT: We report the case of a 16
      year-old patient with an inflammatory myofibroblastic tumor of the mesentery with
      mediastinal metastases. Partial remission was obtained by chemotherapy with
      ifosfamide, dactinomycine, and vincristine. Two months later, relapse with
      infiltration of the meninges developed, and the patient died. CONCLUSION: This
      case demonstrates unusual features of an IMT: presentation with metastases,
      excellent response to chemotherapy, dissemination to the CNS.

PMID- 11574766
TI  - [Multimodal therapy of high-grade gliomas in adults].
AB  - Multimodal Therapy of High Grade Gliomas in Adults For chemotherapy of high-grade
      gliomas only few substances with proven efficacy are available. Today, even the
      newest substances are not proven to be superior to nitrosoureas. Although
      nitrosoureas are still considered as commonly accepted standard treatment, these
      results are based on studies in which response evaluation was not performed
      according to standardized criteria: prognostic criteria were not taken into
      account and statistical power of these studies is limited. However, a lot of
      questions remain to be dealt with and are currently under investigation in
      multicentric randomized studies. Therefore, patients should be encouraged to
      participate in prospectively randomized trials. With or after chemotherapy,
      supportive and palliative care including neurorehabilitation are important to
      improve patients' quality of life.

PMID- 11574767
TI  - [Significance of networking for clinical research in the future].

PMID- 11574768
TI  - [Treatment of multiple myeloma in elderly patients: consensus of the Geriatric
      Oncology Working Group of the German Society of Hematologic Oncology and the
      German Society of Geriatrics].
AB  - Treatment of Multiple Myeloma in the Elderly: Consensus of the Cooperative Group
      of Geriatric Oncology of the DGHO and DGG Multiple myeloma is an illness of old
      age. Often, in elderly people the diagnosis is delayed by the fact that bone
      pain, which is the most frequently presenting symptom, is not correctly
      interpreted because this is a common complaint in the elderly. In contrast to
      younger patients with multiple myeloma, elderly patients often present with
      infections at diagnosis. After the diagnosis is established, careful observation
      is very important. This applies both to patients who require still no therapy and
      to patients under treatment. In order to optimize the care of older patients,
      apart from tumor-specific investigations multidimensional geriatric assessment is
      helpful. This specifically applies for multiple myeloma which predisposes the
      patient to 'instability' and 'immobility', both belonging to the typical
      geriatric symptoms. Geriatric assessment may also be helpful in the selection of
      those elderly patients who are candidates for a possible prognosis-improving
      experimental intense chemotherapy. For the majority of the elderly patients in
      need of treatment the standard is melphalan/prednisone accompanied by one of the
      biphosphonates. Nevertheless, in order to improve prospects also for this group
      of patients, as many elderly patients as possible should be included into
      studies. This is the only way to compile valid recommendations for the treatment
      of elderly patients with multiple myeloma.

PMID- 11574769
TI  - [Quality management and certification in oncology].

PMID- 11574770
TI  - Documentation of normal and leukemic myelopoietic progenitor cells with high
      resolution phase-contrast time-lapse cinematography.
AB  - The high-resolution phase-contrast, time-lapse cinematography using oil immersion
      lenses and 16-mm film demonstrates the kinetic cell events as maturation,
      locomotion, mitosis, and apoptosis of cells cultivated at 37 degrees C for up to
      10 days. 0.5 v/v frozen-thawed sera with presumably high cytokine concentrations
      were added to the plasma or agar clot. Vital progenitor cells from human bone
      marrow and blood have a large, bright, unstructured nucleus with a large
      nucleolus and a narrow rim of cytoplasm (nuclear/cytoplasmic volume ratio = 0.7).
      Their nuclei are 6-14 micrometer in diameter and double their volume within 8 h.
      Many (70%) move at a mean speed of 2 micrometer/min, and many (30%) multiply with
      alpha-2alpha mitoses, generating progenitor cell families. Various disturbances
      during the course of mitosis lead to the formation of polyploid cells, thereby
      yielding the megakaryocytic cell line. Some of the progenitor cells undergo
      asymmetric alpha-alphan mitoses: One of the two initially identical daughter
      cells remains a progenitor cell in the morphological sense, whereas the other
      daughter cell - depending on the size of its mother cell - matures in the same
      culture medium to form a granulocytopoietic, monocytopoietic or
      erythrocytopoietic cell line. - In acute myeloid leukemias (AML), the blasts and
      their nuclei are slightly larger than the corresponding progenitor cells and move
      faster (5 micrometer/min). Symmetric alpha-2alpha mitoses permit unlimited
      multiplication of the leukemic blasts if contact with cytotoxic lymphocytes does
      not render them apoptotic. This results in more stromal cells than normal.
      Granulocytopenia, monocytopenia, and anemia occur due to the genetic impairment
      of signaling control for asymmetric alpha-alphan mitoses, and thrombocytopenia
      occurs due to the reduction in polyploidization.

PMID- 11574771
TI  - Chemotherapy for a patient with advanced non-small-cell lung cancer during
      pregnancy: a case report and a review of chemotherapy treatment during pregnancy.
AB  - BACKGROUND: Lung cancer is the most common cause of cancer death in women in the
      USA. Lung cancer arising during pregnancy is rare and has been reported only 15
      times since the 1950s. However, the use of chemotherapy for lung cancer during
      pregnancy has not previously been reported. METHODS: The history, treatment and
      outcome of a patient with stage IV non-small-cell lung carcinoma (NSCLC)
      diagnosed during pregnancy is presented. Previous published reports on lung
      cancer were retrieved by a literature search of Medline and Cancerlit. RESULTS: A
      31-year-old woman was diagnosed as having stage IV NSCLC with bilateral pulmonary
      involvement when 26 weeks pregnant. Her shortness of breath progressed to dyspnea
      at rest on 100% inspired oxygen. Therefore, she was treated with systemic
      chemotherapy using cisplatin and vinorelbine. Despite this treatment, her
      oxygenation declined further over the next 4 days and thus the baby was delivered
      via cesarean section after 27 weeks of gestation. Four cycles of vinorelbine and
      cisplatin have now been administered. Following this treatment, the patient has
      experienced a significant clinical improvement and no longer requires
      supplemental oxygen. No chemotherapy-related adverse effects have been noted in
      the baby. In the 15 previously reported patients with concurrent lung cancer and
      pregnancy, chemotherapy administration during pregnancy has not been described.
      CONCLUSIONS: Treatment of lung cancer with chemotherapy during pregnancy should
      be considered on an individual basis with regard to the stage of the cancer and
      the maturity of the fetus. To our knowledge, the case presented here is the first
      report of a woman receiving chemotherapy for lung cancer while pregnant.

PMID- 11574772
TI  - Isolated central nervous system relapse of non-seminomatous germ cell tumour of
      the testis. A case report and review of the literature.
AB  - Isolated central nervous system (CNS) relapse of non-seminomatous germ cell
      tumour (NSGCT) of the testis has been reported in only 12 patients previously. We
      report a patient with an isolated CNS relapse of NSGCT, following a prior
      systemic relapse. From a review of previous cases, isolated CNS relapse appears
      to be more common in patients with embryonal cell histology (alone or mixed with
      other elements) and occurred after a median of 8.5 months following initial
      presentation. Long-term survival appears possible using multi-modal treatment
      with whole-brain radiotherapy, surgery and/or chemotherapy. However, the optimal
      treatment of isolated CNS relapse remains undefined.

PMID- 11574773
TI  - Late recurrence of a primitive neuro-ectodermal tumor.
AB  - Late recurrences after therapy are rare in primitive neuro-ectodermal tumor
      (PNET). Most recurrences occur within the first 2 years after therapy, although a
      small number of recurrences may occur up to 5 years after therapy. We present a
      rare case of a recurrence of PNET in a 31-year-old woman 17 years after her
      initial presentation. The potential biological implications of this late
      recurrence as well as responses to subsequent therapy, including temozolomide,
      are discussed.

PMID- 11574774
TI  - Evaluation of a standardized protocol of intracavitary recombinant interferon
      alpha-2b in the palliative treatment of malignant peritoneal effusions. A
      prospective pilot study.
AB  - OBJECTIVE: Several schedules with variable doses of intracavitary interferon have
      been proposed for the management of metastatic peritoneal effusions. This
      prospective pilot study evaluated the efficacy of a standardized schedule of
      intraperitoneal interferon alpha(2b). METHODS: In 41 cancer patients with
      malignant ascites a 9-french intraperitoneal catheter was placed under
      sonographic guidance, and ascites was drained until abdominal ultrasound showed
      complete absence of effusion. Interferon alpha(2b), 6 or 9 million units (body
      weight <or= or >50 kg, respectively), was then administered via the tube, which
      was clamped for 6 h. 6 courses were given at 4-day intervals. In comparison with
      pretreatment levels, the 30-day response was classified as complete (CR) = no
      fluid recurrence, partial (PR) = fluid recurrence <50% and no response (NR) =
      >50%. Responders were monitored until fluid recurrence requiring paracentesis.
      RESULTS: 12 patients had CR, 15 PR, 14 NR. Global response (GR) was 65.9%. In
      ovarian cancer, GR was 75% and was not influenced by the quantity of the
      pretreatment daily fluid production. In the other cancers, a pretreatment fluid
      production <or=500 ml/day was associated with a significantly higher response (p
      < 0.05). Patients not showing response within the first 3 courses did not respond
      after the next courses. 60-day GR was 41.5%, 90-day GR was 26.8%. The mean time
      to fluid reaccumulation was 70.5 +/- 75.3 versus 11.4 +/- 4.4 days before
      treatment (p < 0.001). The survival of responders was 38-394 days (mean 131), and
      the average duration of response was 101 days. CONCLUSION: This protocol could be
      reasonably applied to ovarian cancer patients and to patients with other cancers
      having a fluid production of <or=500 ml/day, and it should be stopped if no
      response is observed after 3 courses of treatment.

PMID- 11574775
TI  - Clinical prognostic factors for patients with recurrent head and neck cancer:
      implications for randomized trials.
AB  - The purpose of our study was to determine the clinical prognostic factors for the
      duration of the overall survival from recurrence (OSR) in patients with recurrent
      head and neck squamous-cell carcinoma. We performed a retrospective analysis on
      496 patients treated between 1982 and 1993 at the Antoine Lacassagne Center. The
      significant favorable prognostic factors for the OSR were: initial T(1-2) (p =
      0.008), no initial nodal involvement (p = 0.002), no initial chemotherapy
      exposure (p = 0.002), induction chemotherapy response (p = 0.001), duration of
      disease-free interval (DFI; p = 0.0001), performance status (PS) 0-1 (p = 0.004)
      and local-regional recurrence (p = 0.001). In the multivariate analysis, the
      apparent nonsignificance of all factors apart from the DFI suggested that
      relevant prognostic factors could be embedded in the DFI. Multivariate analysis
      was performed after excluding the DFI. The results indicated that local-regional
      recurrence, PS 0-1 and no initial chemotherapy exposure remained significant
      favorable prognostic factors for the OSR. The advantages of taking into account
      such prognostic factors are to eliminate the patient selection bias and to ensure
      a fairer comparative evaluation of new or already existing agents in recurrent
      head and neck cancer.

PMID- 11574776
TI  - Reduced Fhit expression occurs in the early stage of esophageal tumorigenesis: no
      correlation with p53 expression and apoptosis.
AB  - The FHIT gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a
      candidate tumor suppressor gene involved in multiple tumors, including esophageal
      carcinoma. We analyzed Fhit expression using an immunohistochemical method in
      invasive carcinoma, carcinoma in situ (CIS) and dysplasia, in paraffin sections
      of 75 esophageal squamous cell carcinomas (ESCs) to further elucidate the role of
      Fhit protein in esophageal carcinogenesis. In addition, we also examined whether
      Fhit expression correlated with p53 expression and apoptosis. Compared to
      adjacent normal mucosa, significant loss or reduction of Fhit expression was
      noted in 67 of 75 (89.3%) invasive ESCs, in 13 of 19 (68.4%) CIS lesions, and in
      10 of 23 (43.5%) dysplastic lesions. There was a progressive loss or reduction of
      Fhit expression with progressive increases in the severity of histopathological
      changes (p < 0.001). However, there was no association between Fhit expression
      and clinicopathological findings, including tumor stage, lymph node metastasis,
      or overall survival. Moreover, Fhit expression was not significantly associated
      with p53 expression and apoptosis. These results indicate that abnormal Fhit
      expression is a common event in the early stage of ESC development and may occur
      independently of p53 expression and apoptosis mechanisms.

PMID- 11574777
TI  - Gastric and intestinal phenotypic marker expression in gastric carcinomas and its
      prognostic significance: immunohistochemical analysis of 136 lesions.
AB  - OBJECTIVE: It is well known that both gastric and intestinal phenotypic cell
      markers are expressed in gastric carcinomas, irrespective of their histologic
      type. However, the clinicopathologic significance of these expressions has not
      yet been clarified. METHODS: We analyzed the correlations among gastric and
      intestinal phenotypic marker expression patterns of the tumor, clinicopathologic
      findings and the patient's outcome in 136 advanced gastric carcinomas. RESULTS:
      Phenotypic marker expression was immunohistochemically evaluated using the
      monoclonal antibodies 45M1 (anti-human gastric mucin; HGM), CLH5 (anti-MUC6),
      Ccp58 (anti-MUC2) and 56C6 (anti-CD10). All tumors were classified as gastric
      (G), gastric and intestinal mixed (GI), intestinal (I) or unclassified (UC)
      phenotype. Of the 136 gastric carcinomas, 50 (36.8%), 56 (41.2%), 21 (15.4%) and
      9 (6.6%) were classified as G, GI, I and UC phenotype, respectively. The G
      phenotype tumors were associated with a higher rate of undifferentiated-type and
      infiltrative histology as compared with the I-phenotype tumors (p < 0.05 and p <
      0.001, respectively). Furthermore, both univariate and multivariate analysis of
      survival revealed the G-phenotype tumor to be associated with a significantly
      poorer outcome than the I-phenotype tumor (p < 0.05). CONCLUSION: Our present
      results indicate that the gastric and intestinal phenotypic marker expression
      pattern of tumors, determined by the combination of HGM, MUC6, MUC2 and CD10
      expression, is prognostically useful for patients with gastric carcinoma.

PMID- 11574778
TI  - Expression of p57/Kip2 protein in hepatocellular carcinoma.
AB  - Evaluation of the biological character of carcinomas requires understanding of
      cell cycle regulators. In the present study, we investigated the expression of
      p57 (Kip2) in 90 hepatocellular carcinomas and 66 noncancerous lesions. The
      average p57 labeling index in noncancerous lesions was 72.3 +/- 19.7. The
      labeling index significantly decreased (p < 0.0001) in hepatocellular carcinoma
      (54.9 +/- 19.7). It was significantly lower in hepatocellular carcinoma cases
      with high biological aggressiveness such as advanced stage (p = 0.0041), poor
      differentiation (p < 0.0001), larger size (p = 0.0400), portal invasion (p <
      0.0001), satellite tumor (p = 0.0023), high proliferating activity (p = 0.0002)
      and cyclin D(1) overexpression (p = 0.0416). Furthermore, cases with low p57
      expression showed worse outcomes for disease-free survival in univariate analysis
      (p = 0.0235), although p57 expression could not be recognized as an independent
      prognostic factor. These findings suggest that p57 contributes to the
      downregulation of cell proliferation and to the progression of hepatocellular
      carcinoma.

PMID- 11574779
TI  - Correlation of beta-catenin and cyclin D1 expression in colon cancers.
AB  - OBJECTIVE: Beta-catenin activates transcription by TCF/LEF and has been regarded
      as an oncogene in a wide range of malignant tumors. Among various molecules
      regulated by beta-catenin/Tcf, cyclin D1 is the most likely candidate for
      stimulation of the oncogenic pathway. The association between beta-catenin and
      cyclin D1 was investigated using clinical samples from colorectal cancers.
      METHODS: The expression of beta-catenin and cyclin D1 was investigated by
      immunohistochemical analyses of samples from 70 patients with colorectal cancers.
      In 28 of the fresh tumor samples, beta-catenin protein was separated into soluble
      and insoluble fractions and quantitatively correlated with cyclin D1 protein by
      Western blot analysis. RESULTS: Compared with noncancerous epithelium, beta
      catenin and cyclin D1 were overexpressed (+) in 35 (50%) and 30 cases (43%),
      respectively. Cyclin D1 (+) was observed in 74% (26/35) of beta-catenin (+)
      cases, but only in 11% (4/35) of the beta-catenin (-) cases. Thus, there was a
      strong association between the expression of beta-catenin and that of cyclin D1
      (p < 0.001). In the Western blot analysis, the amount of cyclin D1 correlated
      well with beta-catenin expression in the soluble fraction (p = 0.0016), but not
      with beta-catenin in the insoluble fraction or with E-cadherin expression. Beta
      catenin (-)/cyclin D1 (-) cases displayed less tumor invasion than the remaining
      cases. However, there were no significant differences in lymph node metastasis or
      other clinicopathological findings. CONCLUSION: Our results indicate that beta
      catenin overexpression in the cytoplasm may promote malignant transformation by
      triggering cyclin D1 expression in colorectal cancers.

PMID- 11574781
TI  - Evaluation of polysaccharopeptide effects against C6 glioma in combination with
      radiation.
AB  - Long-term control of high-grade brain tumors is rarely achieved with current
      therapeutic regimens. The major goal of this study was to determine whether
      polysaccharopeptide (PSP), a crude polysaccharide peptide extract derived from
      Coriolus versicolor, a fungus, could enhance the effects of radiation against
      glioma cells in culture and in xenografted tumors in vivo. PSP significantly
      augmented radiation-induced damage to C6 rat glioma cells in vitro. Nude mice
      injected subcutaneously with the C6 cells were treated with PSP (injected
      intraperitoneally at 2 mg/injection) and radiation (2 Gy/fraction, 8 Gy in total)
      using three different time-dose protocols. Tumor volumes were consistently
      smaller in all treated groups compared to the non-treated tumor-bearing controls
      except in one group which received PSP prior to tumor implantation. The
      administration of radiation alone resulted in the slowest tumor progression,
      whereas PSP alone had no effect. Furthermore, PSP in combination with radiation
      treatment did not increase radiation efficacy. Natural killer cell, lymphocyte
      and granulocyte counts in blood and spleen were significantly higher in PSP
      treated animals, demonstrating that PSP has protective effects on immunological
      function. Collectively, these results warrant further investigation to determine
      if PSP can be effectively utilized to upregulate immune responsiveness in case of
      neoplasia and other diseases in which immunosuppression is a prominent feature.

PMID- 11574780
TI  - A novel 9-aza-anthrapyrazole effective against human prostatic carcinoma
      xenografts.
AB  - OBJECTIVES: Systematic investigation of a novel series of intercalating agents, 9
      aza-anthrapyrazoles, has led to the identification of a promising analogue, BBR
      3438. This study describes the antitumour efficacy of the novel compound in human
      prostate carcinoma models and the molecular/cellular basis of its activity.
      METHODS AND RESULTS: The novel 9-aza-anthrapyrazole BBR 3438 was significantly
      more effective than doxorubicin and losoxantrone (DuP-941) in two of the three
      tested prostate carcinoma models. The superior activity was more evident in PC3
      tumour, since BBR 3438 produced an appreciable rate of complete tumour
      regressions. Under these conditions, the drug-induced antiproliferative activity
      paralleled delayed apoptosis. Tumour response to in vivo drug treatment was
      associated with an early down-regulation of Bcl-2, which was somewhat more marked
      for the aza compound. In fact, the 9-aza-anthrapyrazole induced DNA cleavage in
      vitro with isolated DNA topoisomerase II (isoform alpha) and DNA strand breaks in
      prostatic carcinoma cells. Although the molecular effects of losoxantrone and the
      9-aza analogue on the enzyme target were comparable, the cytotoxic effects of BBR
      3438 could be enhanced by long-term exposure as a consequence of favourable
      cellular accumulation and prominent DNA-binding affinity. In addition, a lower
      reduction potential of the 9-aza-anthrapyrazole in comparison with classical
      anthrapyrazoles suggests an increased ability of the drug to induce oxidative
      stress following free radical production, which may be a contributing factor in
      determining the long-term response (i.e. delayed cell death) to genotoxic damage.
      CONCLUSIONS: BBR 3438 exhibited a unique profile of preclinical activity with a
      superior efficacy against prostatic carcinoma models compared to reference
      compounds (doxorubicin and losoxantrone). The antitumour efficacy of BBR 3438
      against prostatic carcinoma could be the result of a combination of favourable
      events, including enhanced intracellular accumulation and an increased DNA
      binding affinity favouring the accumulation of multiple sublethal or lethal
      damage. In spite of its enhanced cytotoxic potency, the 9-aza compound was better
      tolerated in vivo than losoxantrone, thus improving the therapeutic index. The
      preclinical profile of efficacy against prostatic carcinoma, a tumour resistant
      to conventional antitumour drugs, makes the novel 9-aza-anthrapyrazole BBR 3438 a
      promising candidate for clinical evaluation.

PMID- 11574782
TI  - Statin therapy and stroke prevention.
AB  - Hypercholesterolemia has not traditionally been considered an important risk
      factor in the pathogenesis of stroke. However, recent studies show that statin
      therapy significantly reduces ischemic stroke for patients with established
      coronary artery disease. Statin therapy may reduce stroke through amelioration of
      precerebral atherosclerosis in the carotid artery and the aorta. Anti
      atherosclerotic, anti-inflammatory, and antithrombotic actions of statins occur
      within the blood and in plaque. Statins may also protect against cerebral
      ischemia through beneficial modulation of the brain endothelial nitric oxide
      system. Ongoing studies are exploring the role of statin therapy in the primary
      prevention of stroke and in the prevention of cognitive decline and multi-infarct
      cerebrovascular disease.

PMID- 11574783
TI  - Endovascular repair of lesions of descending thoracic aorta: aneurysms and
      dissections.
AB  - The morbidity and mortality of open repair of descending thoracic aortic lesions
      remains uncomfortably high. Shortly after the advent of an endovascular approach
      for infrarenal abdominal aortic aneurysms, attempts have been made to apply
      similar technologies to the thoracic aorta. Early experiences with endovascular
      grafts for thoracic aortic aneurysms have met with good to moderate success but
      have provided a framework for development of improved technologies specifically
      designed for this anatomic region. Early studies with second generation devices
      have shown more promise. Aortic dissections, a disease state associated with an
      exceptionally high morbidity and mortality, represent another condition that is
      readily treated with an endovascular approach.

PMID- 11574784
TI  - Recent advances in myocardial contrast echocardiography.
AB  - Myocardial contrast echocardiography (MCE) has undergone many advances in the
      past several years through remarkable developments in contrast agent and
      ultrasound equipment technology. Microbubble ultrasound contrast agents can now
      safely transit the pulmonary circulation to provide opacification of the left
      ventricular cavity, improved endocardial border definition, and detection of
      myocardial perfusion. The role of contrast echocardiography in enhancing
      technically difficult images is now well established in clinical practice, and
      has proven especially useful in the stress and intensive care unit settings.
      Major progress has been made in the application of MCE for myocardial perfusion
      assessment in acute and chronic ischemic heart disease syndromes, and comprises
      the focus of this review. Advances in novel applications of contrast
      echocardiography, including targeted delivery of genetic and pharmaceutical
      materials, have also occurred, but remain in a preclinical phase. In summary, the
      combination of recent innovations in ultrasound equipment, and microbubble
      acoustics, allows for exciting exploration of the expanding role of contrast
      echocardiography in clinical practice.

PMID- 11574785
TI  - Echocardiographic assessment of diastolic function.
AB  - Abnormal diastolic function is increasingly appreciated as a major contributor to
      cardiac morbidity and mortality. Accurate noninvasive assessment of the presence
      and severity of diastolic impairment is crucial to the broad application and
      understanding of this common condition. Echocardiographic parameters have become
      the backbone of this noninvasive assessment. Active investigation into both old
      and new Doppler variables will provide the framework that can lead to a more
      uniform assessment and reporting that will be essential as we prepare to confront
      clinically the next frontier in cardiac pathophysiology. This review discusses
      the clinical impact of recent echocardiographic contributions to the field of
      diastology.

PMID- 11574786
TI  - Echocardiographic evaluation of mitral regurgitation.
AB  - Accurate evaluation of mitral regurgitation (MR) severity remains a challenging
      task in clinical cardiology. The importance of proper quantification of
      regurgitation cannot be underestimated because a delayed decision to replace or
      repair a defective valve may lead to worsening ventricular function and increased
      perioperative and long-term mortality. In this review we discuss both recent
      developments in the quantification of MR as well as new insights into the
      pathophysiology and progression of this lesion.

PMID- 11574787
TI  - Genetic predisposition to coronary artery disease.
AB  - Understanding the genetic basis of coronary artery disease (CAD) can improve
      management and prevention. Family and twin studies, animal models and gene
      association studies support a genetic basis for CAD. Genes contribute to CAD
      development and progression, and response to risk factor modification and
      lifestyle choices. Family history is the best indicator of a predisposition to
      CAD and further refinement is possible with biochemical and DNA testing. Many
      inherited cardiovascular risk factors can be modified, such as LDL cholesterol,
      homocysteine and lipoprotein(a). Early detection of CAD might lead to earlier
      intervention for genetically susceptible individuals. However, data are lacking
      regarding the efficacy of this approach in preventing clinical events. Despite
      this lack of evidence, knowledge of genetic CAD susceptibility has value in
      providing risk information and guiding decision making. Further research that
      investigates outcomes regarding genetic risk assessment for CAD is necessary.

PMID- 11574788
TI  - Triglycerides: risk factor or fellow traveler?
AB  - An unresolved issue in preventive cardiology is whether the serum triglyceride
      level is an independent risk factor for coronary heart disease and, as a direct
      practical consequence, whether it has value as a diagnostic test. Evidence
      published in the past year has contributed substantially to clarifying these
      issues. In this review, we discuss the data that bears upon the importance of
      triglycerides as a risk factor and the implications of recent clinical trials
      directed at lipid lowering. We then discuss the alternatives for triglyceride
      lowering therapy in the light of this new knowledge.

PMID- 11574789
TI  - Pediatric cardiology in a digital world.

PMID- 11574790
TI  - An emergency department-based randomized trial of nonbronchoscopic
      bronchoalveolar lavage for early pathogen identification in severe community
      acquired pneumonia.
AB  - STUDY OBJECTIVES: Many patients with community-acquired pneumonia are treated
      empirically without an aggressive search for causative pathogens, an approach
      adopted largely because of the costs and difficulties encountered during efforts
      to identify the causative organisms. Blood and sputum cultures are not sensitive,
      and the more invasive techniques of bronchoscopy and lung biopsy are generally
      time consuming and not cost-effective. The technique of nonbronchoscopic
      bronchoalveolar lavage (BAL) has been shown to accurately diagnose the causes of
      nosocomial pneumonia. The purpose of this study was to determine whether an
      emergency department-based BAL protocol would lead to more frequent isolation of
      pneumonia pathogens and result in more changes to tailored antibiotic therapy in
      comparison with standard care. METHODS: We studied all adult patients admitted
      with a diagnosis of pneumonia who were tracheally intubated and who had
      obtainable familial consent in the ED of an urban county hospital from March 1998
      to October 1999. Exclusions included antibiotic use within the past 5 days,
      pneumothorax, hemoptysis, or persistent hypoxia using 100% oxygen. Patients were
      randomized to standard care versus standard care plus BAL. Blood culture
      specimens were drawn from all patients before the initiation of antibiotics. All
      other diagnostic tests were ordered at the discretion of treating physicians. BAL
      fluid, sputum, and blood culture specimens were tracked, and patient antibiotic
      course was followed to assess any change in regimen. RESULTS: Twenty-six of 64
      patients evaluated for study participation met all eligibility criteria; 14
      patients received standard care, and 12 patients received standard care plus BAL.
      Pneumonia pathogens were identified in 10 (83.3%) of 12 patients in the BAL group
      and in 4 (28.6%) of 14 patients in the standard care group (P =.007). Comparing
      BAL versus non-BAL groups, there was no significant difference in the likelihood
      of overall antibiotic regimen changes (P =.149), but there was a difference with
      regard to antibiotic changes made in patients with positive culture test results
      (P =.026). No major complications occurred with BAL catheterizations. CONCLUSION:
      ED-based BAL catheterization allows for early identification of pathogens in
      severe community-acquired pneumonia, which leads to changes in antibiotic
      therapy.

PMID- 11574791
TI  - Validation of the Ottawa Knee Rules.
AB  - STUDY OBJECTIVE: We sought to validate the Ottawa Knee Rules for determining the
      need for radiography in patients with acute knee injury. METHODS: A prospective
      cohort study was performed in emergency departments of 11 hospitals of the
      Osakidetza-Basque Country Health Service. The patient population was composed of
      a convenience sample of 1,522 eligible adults of 2,315 patients with acute knee
      injuries. The attending emergency physicians assessed each patient for
      standardized clinical variables and determined the need for radiography according
      to the decision rule. Radiography was performed in each patient, irrespective of
      the determination of the rule, after clinical evaluation findings were recorded.
      The rule was assessed for the ability to correctly identify fracture of the knee.
      RESULTS: The decision rule had a sensitivity of 1.0 (95% confidence interval [CI]
      0.96 to 1.0), identifying 89 patients with clinically important fractures. The
      potential reduction in use of radiography was estimated to be 49%. The
      probability of fracture, if the decision rules were negative, is estimated to be
      0% (95% CI 0% to 0.5%). CONCLUSION: Prospective validation has shown the Ottawa
      Knee Rules to be 100% sensitive for identifying fractures of the knee and to have
      the potential to allow physicians to reduce the use of radiography in patients
      with acute knee injuries.

PMID- 11574792
TI  - Psychologic morbidity and health-related quality of life of patients assessed in
      a chest pain observation unit.
AB  - STUDY OBJECTIVES: We sought to measure psychologic morbidity and health-related
      quality of life among patients attending the hospital with acute chest pain both
      at presentation and 1 month after rigorous assessment for cardiac disease.
      METHODS: Consecutive patients undergoing assessment on the chest pain observation
      unit of a large, urban emergency department were asked to complete 3
      questionnaires: the Short Form-36 Health Survey (SF-36), the Euroqol Health
      Utility Questionnaire, and the Hospital Anxiety and Depression Scale. The same
      questionnaires were mailed 1 month later, along with a questionnaire documenting
      subsequent pain and reassurance. RESULTS: At enrollment (n=166), 32 (19%)
      participants (95% confidence interval [CI] 15% to 26%) were experiencing moderate
      levels of anxiety, and 21 (13%, 95% CI 8% to 19%) were experiencing moderate
      levels of depression. Health utility and all SF-36 dimensions of quality of life
      were substantially below age-adjusted normal values. One month after assessment
      (n=110), only the Pain dimension score of SF-36 had significantly improved. Most
      scores were unchanged, and the Physical Role and Mental Health dimension scores
      of SF-36 had significantly deteriorated. Seventy (64%) patients (95% CI 54% to
      72%) had further pain after discharge. Despite these findings, 98 (86%) patients
      (95% CI 78% to 91%) responded that their assessment was "completely reassuring"
      or "quite reassuring." CONCLUSION: Patients with acute, undifferentiated chest
      pain have substantial psychologic morbidity and impairment of quality of life.
      Although patients respond that they are reassured by chest pain observation unit
      assessment, anxiety and depression remain prevalent and quality of life remains
      impaired 1 month after assessment.

PMID- 11574793
TI  - Bedside echocardiography by emergency physicians.
AB  - STUDY OBJECTIVE: Timely diagnosis of a pericardial effusion is often critical in
      the emergency medicine setting, and echocardiography provides the only reliable
      method of diagnosis at the bedside. We attempt to determine the accuracy of
      bedside echocardiography as performed by emergency physicians to detect
      pericardial effusions in a variety of high-risk populations. METHODS: Emergency
      patients presenting with high-risk criteria for the diagnosis of pericardial
      effusion underwent emergency bedside 2-dimensional echocardiography by emergency
      physicians who were trained in ultrasonography. The presence or absence of a
      pericardial effusion was determined, and all images were captured on video or as
      thermal images. All emergency echocardiograms were subsequently reviewed by the
      Department of Cardiology for the presence of a pericardial effusion. RESULTS:
      During the study period, a total of 515 patients at high risk were enrolled. Of
      these, 103 patients were ultimately deemed to have a pericardial effusion
      according to the comparative standard. Emergency physicians detected pericardial
      effusion with a sensitivity of 96% (95% confidence interval [CI] 90.4% to 98.9%),
      specificity of 98% (95% CI 95.8% to 99.1%), and overall accuracy of 97.5% (95% CI
      95.7% to 98.7%). CONCLUSION: Echocardiography performed by emergency physicians
      is reliable in evaluating for pericardial effusions; this bedside diagnostic tool
      may be used to examine specific patients at high risk. Emergency departments
      incorporating bedside ultrasonography should teach focused echocardiography to
      evaluate the pericardium.

PMID- 11574794
TI  - The injury pattern of a new law enforcement weapon: the police bean bag.
AB  - STUDY OBJECTIVE: This case series describes the injury pattern of the police bean
      bag, a new weapon adopted by US law enforcement agencies. METHODS: Retrospective
      chart review between 1996 and 2000 identified bean bag injuries. Autopsy data
      were gathered for 1 fatality. Circumstances of the shootings, toxicology results,
      and psychiatric diagnoses, if any, were recorded. RESULTS: Thirty-nine men and 1
      woman between the ages of 16 and 77 years were shot by officers of either the Los
      Angeles Police Department or the Los Angeles Sheriff's Department. The fatality
      was caused by massive hemothorax after thoracic penetration. The locations of
      serious penetrating injuries included the thoracic cavity, eye, abdomen, arm, and
      leg. Blunt injuries included splenic rupture, pneumothorax, compartment syndrome,
      testicular fracture, subcapsular liver hematoma, and cardiac contusion.
      Complications included hemothorax, pneumopericardium, wound infection,
      compartment syndrome, and osteomyelitis. Psychiatric consultation was requested
      for 27 (69.2%) of 39 surviving patients. The Diagnostic and Statistical Manual of
      Mental Disorders, fourth edition (DSM-IV) Axis I was used for diagnosis in all 27
      patients. Psychosis was diagnosed in 16 (59.3%), suicidal ideation in 15 (55.6%),
      and major depression in 6 (22.2%) of the 27 cases. Schizophrenia had previously
      been diagnosed in 7 (25.9%) of the 27 cases. All but 1 of the patients had
      toxicology screenings performed, and the results of 29 (74.4%) of 39 were
      positive. Of these 29 positive results, 15 (51.7%) were positive for alcohol and
      8 (27.6%) were positive for cocaine. CONCLUSION: Awareness of the broad scope of
      potential injuries mandates a thorough evaluation of both blunt and penetrating
      trauma in patients shot with police bean bags. The scope of these injuries raises
      significant public health considerations because use of this weapon has been
      adopted by law enforcement agencies in all 50 states and at least 10 countries.

PMID- 11574795
TI  - Emergency department evaluation of acute stress disorder symptoms in violently
      injured youths.
AB  - STUDY OBJECTIVE: We assess the feasibility of evaluating acute stress disorder
      (ASD) symptoms in the emergency department and provide an initial estimate of the
      prevalence, severity, and variability of these symptoms in violently injured
      urban children and young adults. METHODS: The Immediate Stress Response Checklist
      (ISRC) was administered to violently injured patients between the ages of 8 and
      24 years who presented to 2 urban, academic medical center EDs during a 10-week
      period. The ISRC is designed to assess ASD symptoms in children and youths
      immediately after a traumatic event. Responses are described using summed symptom
      severity scores and counts of symptoms. RESULTS: Out of 109 identified youths, 81
      participated. Fear, helplessness, or horror during the injury event was reported
      by 59 (73%) of study participants. Each of the following categories of ASD
      symptoms was reported by a significant number of youths: peritrauma dissociation,
      63 (78%); posttrauma dissociation, 33 (41%); re-experiencing intrusive thoughts
      or images, 66 (82%); avoidance, 53 (65%); and hyperarousal, 32 (39%). The ISRC
      demonstrated high internal consistency (Cronbach alpha=.88) in this cohort.
      CONCLUSION: The ISRC can be used to assess acute stress reactions in violently
      injured youths in the immediate period after injury. Although these reactions
      appear to be common, there is substantial variability among distinct symptom
      categories. These results support the need for further investigation of the
      relationship between immediate stress responses and longer-term emotional impact
      of violent injury. Clinicians should consider assessing the emotional responses
      of children and adolescents who are injured by interpersonal violence, even when
      these injuries seem minor.

PMID- 11574796
TI  - Monitoring a clinical trial conducted under the Food and Drug Administration
      regulations allowing a waiver of prospective informed consent: the diaspirin
      cross-linked hemoglobin traumatic hemorrhagic shock efficacy trial.
AB  - In 1996, the US Food and Drug Administration (FDA) enacted Rule 21 CFR section
      50.24, which allows a narrow exception to the requirement for prospective
      informed consent from human research subjects in clinical trials investigating
      potentially beneficial therapies for acute, life-threatening conditions. The
      first clinical trial to be conducted under this rule was sponsored by Baxter
      Healthcare Corporation and approved by the FDA on November 21, 1996. This large,
      multicenter, randomized clinical trial was designed to compare the addition of
      diaspirin cross-linked hemoglobin (DCLHb) with standard care in the initial
      resuscitation of adults experiencing severe, uncompensated, traumatic hemorrhagic
      shock. Before the first planned interim analysis of the data, review of fatal
      adverse events revealed an imbalance in mortality between the 2 treatment groups.
      The Data Monitoring Committee (DMC) recommended suspension of patient enrollment
      24 days later. Additional data collection and analyses confirmed the excess
      number of deaths in patients treated with DCLHb but failed to reveal the cause of
      these deaths. The trial was formally terminated after only 112 of the planned 850
      patients had been enrolled. We review the events leading up to and the rationale
      behind the DMC recommendations for suspension of patient enrollment and trial
      termination. Although the DCLHb trial was unsuccessful in achieving its goals,
      the monitoring process worked well. Emergency research was facilitated by DMC
      oversight, and the interests of research subjects were protected by the actions
      of the DMC.

PMID- 11574797
TI  - Injury prevention and control in children.
AB  - Injury is the number one cause of death and life-years lost for children. In
      children, injury mortality is greater than childhood mortality from all other
      causes combined. Modern injury prevention and control seeks to prevent and limit
      or control injuries through the 4 Es of injury prevention: engineering,
      enforcement, education, and economics. Emergency physicians are often placed in a
      critical role in the lives of individuals, are respected authorities on the
      health and safety of children and adults, and have daily exposure to high-risk
      populations. This gives emergency physicians a unique perspective and an
      opportunity to take an active role in injury control and prevention. Specific
      methods or strategies for promulgating injury prevention and control in our
      emergency medicine practices are suggested, ranging from education (for our
      patients and health professionals); screening and intervention for domestic
      violence, child maltreatment, drug-alcohol dependency and abuse; data collection;
      reporting unsafe products; research; legislation; serving in regulatory and
      governmental agencies; emergency medical services-community involvement; and
      violence prevention. Emergency physicians can play a significant role in
      decreasing pediatric injury and its concomitant morbidity and mortality.

PMID- 11574798
TI  - Alcohol-related motor vehicle crashes: deterrence and intervention.
AB  - Impaired driving continues to be a major factor in many injuries and fatalities
      on our nation's highways. In 1998, alcohol was involved in 38% of all fatal
      crashes, contributing to 15,935 deaths. The combination of improved public
      awareness and strong legal sanctions for driving under the influence has been
      shown to reduce the incidence of impaired driving. A few states have instituted
      new statutes for mandatory health care reporting of impaired drivers who have
      been involved in motor vehicle crashes. Current research into establishing
      emergency department-based effective, efficient, and "user-friendly" methods for
      screening, intervention, and referral on behalf of the problem drinker offers
      promise for emergency physicians to become empowered to better manage this
      individual and public health problem. Emergency physicians may soon need to
      reassess their role in reducing the occurrence of alcohol-related motor vehicle
      crashes through widespread screening, intervention, and referral of these
      patients.

PMID- 11574799
TI  - Community-level firearm injury surveillance: local data for local action.
AB  - In the United States, firearms are used to commit homicide more frequently than
      all other methods combined. According to the US Department of Justice, firearms
      are used to commit more than 1 million crimes each year. Despite the magnitude of
      this problem, little is known about the epidemiology of firearm crimes and
      assaults. Many states require medical personnel to report all nonfatal shootings
      to law enforcement, but the rate of compliance with this requirement is unknown.
      To enhance cooperation between community emergency departments and law
      enforcement agencies, we created a unified firearm injury notification system for
      the City of Atlanta, Georgia, and 5 surrounding counties: Fulton, DeKalb, Cobb,
      Gwinnett, and Clayton. Our findings are reported here.

PMID- 11574800
TI  - Emergency medicine and police collaboration to prevent community violence.
AB  - An important responsibility of emergency departments is the management of
      injuries sustained in assaults. Most assaults, including many causing serious
      injury, are not reported and not recorded by the police. This is important
      because police investigation and the conviction of offenders has a substantial
      deterrent effect and because information about the circumstances of intentional
      injury is key to prevention. Recent investigation of ED-police collaboration has
      shown that many of the injured, and ED staff want offenses to be reported but
      that there are attitudinal, logistic, and ethical-legal obstacles to achieving
      this. Organized joint efforts by emergency medicine personnel and police
      departments, on the basis of a sound legal and ethical framework to protect the
      rights of both victims and offenders, should deter more violent offenders and
      would-be violent offenders. They also provide the police with unique aggregate,
      nonconfidential information that is of substantial help in tackling violence. ED
      data can be used to measure and refine violence prevention initiatives and are
      being developed as the basis of a new, independent measure of police performance.
      Strategies, practical ideas to overcome obstacles, and directions for future
      research are suggested.

PMID- 11574801
TI  - Docs and cops: a collaborating or colliding partnership?

PMID- 11574802
TI  - Emergency medicine in Japan.
AB  - We describe the development and current state of the practice of acute care
      medicine in Japan. Included are descriptions of the structure and organization of
      the critical care transfer system, out-of-hospital care system, and hospital
      classification. We also outline the training and equipment necessary for the
      various levels of out-of-hospital care providers, as well as that needed for
      certification as an emergency physician.

PMID- 11574803
TI  - Airway compromise secondary to lingual hematoma complicating administration of
      tissue plasminogen activator for acute ischemic stroke.
AB  - Hemorrhagic complications of tissue plasminogen activator (tPA) are well known.
      We report a case of a lingual hematoma that developed after tPA administration
      for an acute ischemic stroke that necessitated orotracheal intubation to maintain
      the patient's airway. This case demonstrates the need for thorough
      preadministration physical examination, as well as careful monitoring during
      infusion and after administration of this potent therapeutic agent.

PMID- 11574804
TI  - Poststreptococcal glomerulonephritis presenting as impending airway obstruction.
AB  - The presence of poststreptococcal glomerulonephritis in the pediatric patient
      remains a diagnostic challenge to the emergency physician. The variability of
      both patient presentation and laboratory parameters often obscures the diagnosis.
      We describe a child who presented to the emergency department with subglottic
      edema and the possibility of impending airway compromise. The child was admitted
      to the hospital under close observation, and several days later, the diagnosis of
      poststreptococcal glomerulonephritis was made.

PMID- 11574805
TI  - Commentary: automatic collision notification: ready or not, here it comes.

PMID- 11574808
TI  - Elevated blood lead levels in urban moonshine drinkers.

PMID- 11574809
TI  - American College of Emergency Physicians. Use of ultrasound imaging by emergency
      physicians.

PMID- 11574810
TI  - American College of Emergency Physicians. ACEP emergency ultrasound guidelines
      2001.

PMID- 11574811
TI  - American College of Emergency Physicians. Bloodborne infections in emergency
      medicine.

PMID- 11574812
TI  - American College of Emergency Physicians. Boarding of admitted and intensive care
      patients in the emergency department.

PMID- 11574813
TI  - American College of Emergency Physicians. Expert witness guidelines for the
      specialty of emergency medicine.

PMID- 11574814
TI  - American College of Emergency Physicians. Managed health care organizations and
      emergency care.

PMID- 11574815
TI  - The biology of aging.

PMID- 11574816
TI  - Histamine stimulates alveolar macrophages to release neutrophil and monocyte
      chemotactic activity.
AB  - Histamine and serotonin are important inflammatory mediators in the
      pathophysiology of asthma, and asthmatic patients have higher plasma histamine
      and serotonin levels than non-asthmatic control subjects. Alveolar macrophages
      (AMs) synthesize and secrete a large number of substances that play a key role in
      acute and chronic inflammation including asthma. We postulated that AMs might
      release chemotactic activity for neutrophils and monocytes in response to
      histamine or serotonin. To test this hypothesis, bovine AMs were cultured, and
      the supernatant fluids were evaluated for neutrophil chemotactic activity (NCA)
      and monocyte chemotactic activity (MCA) by a blind well chamber technique. AMs
      released chemotactic activity in response to histamine and serotonin in a dose-
      and time-dependent manner (P <.05). Partial characterization and molecular sieve
      column chromatography revealed that low-molecular-weight lipid-soluble activity
      was predominant. Lipoxygenase inhibitors significantly blocked the release of
      chemotactic activity. Leukotriene B(4) receptor antagonists blocked the
      chemotactic activity. Immunoreactive leukotriene B(4) significantly increased in
      supernatant fluids in response to histamine and serotonin. The receptor
      responsible for the release of chemotactic activity in response to histamine was
      the H2 receptor. These data demonstrate that AMs release NCA and MCA in response
      to histamine or serotonin (or both) and may modulate the inflammatory cell
      recruitment into the lung.

PMID- 11574817
TI  - E-cadherin is essential for gastric epithelial restitution in vitro: a study
      using the normal rat gastric mucosal cell line RGM1.
AB  - The proliferation and migration of epithelial cells appear to have important
      roles in intercellular adhesion and the regeneration of gastric mucosal lesions.
      However, the role of E-cadherin, an important intercellular adhesion molecule, in
      restitution after gastric mucosal damage is unknown. This study was designed to
      investigate the possible role of E-cadherin in the regeneration of gastric
      mucosal lesions. Artificial small wounds were made in an RGM1 confluent monolayer
      sheet, and the healing process was monitored with or without the presence of
      different concentrations of anti-E-cadherin antibodies. E-cadherin mRNA and
      protein expression were determined by Northern blot analysis and immunostaining,
      respectively. Epithelial restitution in anti-E-cadherin antibody-treated
      monolayers was inhibited as compared with that in the controls without antibody.
      E-cadherin mRNA and protein expression were up-regulated transiently during the
      healing process. E-cadherin plays an important role during wound healing of
      gastric epithelial lesions and is crucial for sheet migration.

PMID- 11574818
TI  - Amphotericin B decreases adenylyl cyclase activity and aquaporin-2 expression in
      rat kidney.
AB  - The present study was intended to examine whether the amphotericin-induced
      urinary concentration defect can be related to an altered regulation of aquaporin
      (AQP) water channels in the kidney. Male Sprague-Dawley rats were injected with
      amphotericin B (6 mg/kg/d, IP ) for 21 days. The protein expression of AQP1-3,
      Gsalpha, and adenylyl cyclase was determined in the kidney. To further specify
      the primary point of dysregulation of AQP channels that are activated by the
      arginine vasopressin/cyclic adenosine monophosphate (AVP/cAMP) pathway, different
      components of adenylyl cyclase complex were separately examined for their cAMP
      generating activities. Amphotericin treatment resulted in kidney failure
      associated with decreased tubular water reabsorption and increased urinary flow
      rate. The expression of AQP2 proteins was significantly decreased in the outer
      medulla and inner medulla but not in the cortex. The expression of AQP2 proteins
      in the membrane fraction changed in parallel with that in the cytoplasmic
      fraction, suggesting a preserved targeting. Neither the expression of AQP1 nor
      that of AQP3 was significantly affected in the cortex, outer medulla, or inner
      medulla. The cAMP generation in response to AVP or sodium fluoride was decreased,
      whereas that to forskolin was not significantly altered. The expression of
      Gsalpha proteins was decreased in the inner medulla, whereas that of adenylyl
      cyclase VI remained unaltered. These findings indicate that the amphotericin
      induced urinary concentration defect may in part be causally related to a reduced
      abundance of AQP2 channels in the kidney. It is also suggested that the primary
      impairment in the pathway leading to the activation of AQP channels that are
      regulated by the AVP/cAMP pathway lies at the level of G proteins.

PMID- 11574819
TI  - Zinc activates NF-kappaB in HUT-78 cells.
AB  - Zinc is essential for human health, and its deficiency in human beings results in
      growth failure, immune disorders affecting Th1 functions, decreased interleukin-2
      (IL-2) production, and cognitive impairment. Nearly 2000 transcription factors
      require zinc for their structural integrity; however, it is not known whether
      cellular zinc deficiency results in any change in activation of any of the
      transcription factors. Inasmuch as NF-kappaB binds to the promoter enhancer area
      of IL-2 and IL-2Ralpha genes, we investigated the effect of zinc deficiency on
      activation of NF-kappaB and its binding to DNA in HUT-78, a Th0 malignant human
      lymphoblastoid cell line. We show here for the first time that in zinc-deficient
      HUT-78 cells, phosphorylated IkappaB, and IKK, ubiquitinated IkappaB and binding
      of NF-kappaB to DNA were all significantly decreased. Zinc increased the
      translocation of NF-kappaB from cytosol to nucleus. We also demonstrate that the
      binding of recombinant NF-kappaB (p50)(2) to DNA in HUT-78 cells was zinc
      specific. We conclude that zinc plays an important role in the activation of NF
      kappaB in HUT-78 cells.

PMID- 11574820
TI  - Colon epithelial cellular protein induces oral tolerance in the experimental
      model of colitis by trinitrobenzene sulfonic acid.
AB  - Rectal administration of trinitrobenzene sulfonic acid (TNBS) produces chronic
      colitis in experimental animals. However, the role of epithelial cellular
      protein(s) in this model is unknown. We examined whether oral tolerance can be
      induced in this model with colon epithelial cell proteins and whether it is organ
      specific. Rats were fed five times with extracts of LS-180 human colon cancer
      cells or HT 1080 human fibroblast cells. Syngeneic normal rat colon or small
      intestinal extracts were fed to separate groups of rats. After oral feedings,
      each rat received TNBS by enema. Rats were killed 15 days later, and the
      following were measured: gross and histologic disease score, weight, thickness,
      and myeloperoxidase values of colon and serum interferon-gamma (IFN-gamma) and
      transforming growth factor-beta (TGF-beta) levels. Rectal TNBS alone produced
      severe colitis with a 26% mortality rate. Rats fed LS-180 or rat colon extract
      before TNBS enema were protected, as evidenced by reductions in mortality rate,
      disease scores, and myeloperoxidase values. However, rats fed HT 1080 or small
      intestine extract lacked such protection. To examine the possible mechanism of
      the oral tolerance, T lymphocytes from mesenteric lymph nodes and spleen of LS
      180 extract-fed rats were passively transferred to naive rats, and this was
      followed by TNBS enema. These rats showed clear protection. Protected animals had
      low IFN-gamma and high TGF-beta levels. This study demonstrates that cellular
      protein(s) from human colon epithelial cells, but not from human fibroblasts, can
      induce oral tolerance in experimental colitis. This oral tolerance is mediated by
      primed mesenteric and splenic T lymphocytes.

PMID- 11574821
TI  - Role of nitric oxide in acidosis-induced intestinal injury in anesthetized rats.
AB  - We investigated the pathogenic mechanism(s) of small intestinal injury during
      acidosis in relation to circulating nitric oxide (NO) in an experimental rat
      model. Rats were anesthetized, paralyzed, and mechanically ventilated with room
      air. Hydrochloric acid (0.16 mmol bolus followed by 0.132 mmol/kg/h) was infused
      through the jugular vein for 5 hours. Control rats received a saline infusion.
      Arterial blood gases, blood pressure, and blood pH were measured every 30
      minutes. The involvement of NO in this acidosis model was assessed by measuring
      plasma concentration of nitrite/nitrate (NOx) and by evaluating inducible NO
      synthase (iNOS) expression in small intestinal mucosa. Intestinal injury was
      assessed by measuring myeloperoxidase (MPO) activity, thiobarbituric acid
      reactants (TBARS), and histologic scores. HCl infusion was associated with
      hypotension, decreased blood pH, increased plasma concentration of NOx, augmented
      intestinal mucosal iNOS expression, MPO activity, TBARS, and histopathologic
      injury scores. Pretreatment with an iNOS inhibitor, aminoguanidine (AG, 50
      mg/kg), reversed HCl-induced hypotension without a change in blood pH. HCl
      induced lesions, MPO activity, TBARS, and plasma NOx production were decreased by
      AG. Our data show that the pathogenic mechanisms of acidosis-induced small
      intestinal lesions involve up-regulation of NO production by increased expression
      of iNOS and augmentation of superoxide radicals and MPO activity.

PMID- 11574822
TI  - Use of digoxin in diastolic heart failure.

PMID- 11574823
TI  - Carrie Buck's pedigree.

PMID- 11574824
TI  - A new policy on financial disclosure.

PMID- 11574825
TI  - Signal transduction by target-derived neurotrophins.

PMID- 11574826
TI  - pRIMing synaptic vesicles for fusion.

PMID- 11574827
TI  - Moving molecules make synapses.

PMID- 11574828
TI  - Vision to action: new insights from a flip of the wrist.

PMID- 11574831
TI  - Ectopic expression of Olig1 promotes oligodendrocyte formation and reduces
      neuronal survival in developing mouse cortex.

PMID- 11574832
TI  - Rapid formation and remodeling of postsynaptic densities in developing dendrites.
AB  - The dynamics of postsynaptic density (PSD) formation and remodeling were
      investigated in live developing hippocampal tissue slices. Time lapse imaging of
      transfected neurons expressing GFP-tagged PSD95, a prominent PSD protein,
      revealed that up to 40% of PSDs in developing dendrites are structurally dynamic;
      they rapidly (<15 min) appear or disappear, but also grow, shrink and move within
      shafts and spines. New spines containing PSDs were formed by conversion of
      dynamic filopodia-like spine precursors in which PSDs appeared de novo, or by
      direct extension of spines or spine precursors carrying preformed PSDs from the
      shaft. PSDs are therefore highly dynamic structures that can undergo rapid
      structural alteration within dendrite shafts, spines and spine precursors,
      permitting rapid formation and remodeling of synaptic connections in developing
      CNS tissues.

PMID- 11574834
TI  - Reviewing cancer and immunology.

PMID- 11574833
TI  - Japan's beef scandal.

PMID- 11574835
TI  - 'Identity crisis' racks depleted research arms of spy agencies.

PMID- 11574836
TI  - Swift move to collect fallout data.

PMID- 11574837
TI  - Support for science is firm as emergency raises budget.

PMID- 11574838
TI  - Japan's first BSE case fuels fears elsewhere.

PMID- 11574839
TI  - Transgenic corn found growing in Mexico.

PMID- 11574840
TI  - British archaeology boost may uncover old enthusiasm.

PMID- 11574841
TI  - Crushing victory could help in quest for fusion energy.

PMID- 11574842
TI  - China plans 'hybrid' embryonic stem cells.

PMID- 11574846
TI  - All creatures great and small.

PMID- 11574847
TI  - Storm in a culture dish.

PMID- 11574848
TI  - Need for public debate about fertility treatments.

PMID- 11574849
TI  - Risk that websites could break code of anonymity.

PMID- 11574850
TI  - IVF and the history of stem cells.

PMID- 11574864
TI  - Bridge or ravine?

PMID- 11574865
TI  - More than words.

PMID- 11574866
TI  - Once upon an asteroid.

PMID- 11574867
TI  - Human genetics. Testing telomerase.

PMID- 11574869
TI  - Statistical physics. The salesman and the tourist.

PMID- 11574870
TI  - Plant hormones. Transporters on the move.

PMID- 11574871
TI  - Quantum physics. Entangled atomic samples.

PMID- 11574873
TI  - Patrick D. Wall (1925-2001).

PMID- 11574874
TI  - Transatlantic robot-assisted telesurgery.

PMID- 11574875
TI  - Microbiology. Cyanobacteria track water in desert soils.

PMID- 11574876
TI  - Intracellular signalling. Receptor-specific messenger oscillations.

PMID- 11574877
TI  - Hospital waiting-lists. Do power laws imply self-regulation?

PMID- 11574878
TI  - Two-component circuitry in Arabidopsis cytokinin signal transduction.
AB  - Cytokinins are essential plant hormones that are involved in shoot meristem and
      leaf formation, cell division, chloroplast biogenesis and senescence. Although
      hybrid histidine protein kinases have been implicated in cytokinin perception in
      Arabidopsis, the action of histidine protein kinase receptors and the downstream
      signalling pathway has not been elucidated to date. Here we identify a eukaryotic
      two-component signalling circuit that initiates cytokinin signalling through
      distinct hybrid histidine protein kinase activities at the plasma membrane.
      Histidine phosphotransmitters act as signalling shuttles between the cytoplasm
      and nucleus in a cytokinin-dependent manner. The short signalling circuit reaches
      the nuclear target genes by enabling nuclear response regulators ARR1, ARR2 and
      ARR10 as transcription activators. The cytokinin-inducible ARR4, ARR5, ARR6 and
      ARR7 genes encode transcription repressors that mediate a negative feedback loop
      in cytokinin signalling. Ectopic expression in transgenic Arabidopsis of ARR2,
      the rate-limiting factor in the response to cytokinin, is sufficient to mimic
      cytokinin in promoting shoot meristem proliferation and leaf differentiation, and
      in delaying leaf senescence.

PMID- 11574879
TI  - The landing of the NEAR-Shoemaker spacecraft on asteroid 433 Eros.
AB  - The NEAR-Shoemaker spacecraft was designed to provide a comprehensive
      characterization of the S-type asteroid 433 Eros (refs 1,2,3), an irregularly
      shaped body with approximate dimensions of 34 x 13 x 13 km. Following the
      completion of its year-long investigation, the mission was terminated with a
      controlled descent to its surface, in order to provide extremely high resolution
      images. Here we report the results of the descent on 12 February 2001, during
      which 70 images were obtained. The landing area is marked by a paucity of small
      craters and an abundance of 'ejecta blocks'. The properties and distribution of
      ejecta blocks are discussed in a companion paper. The last sequence of images
      reveals a transition from the blocky surface to a smooth area, which we interpret
      as a 'pond'. Properties of the 'ponds' are discussed in a second companion paper.
      The closest image, from an altitude of 129 m, shows the interior of a 100-m
      diameter crater at 1-cm resolution.

PMID- 11574880
TI  - Shoemaker crater as the source of most ejecta blocks on the asteroid 433 Eros.
AB  - The loose material--regolith--on the surfaces of asteroids is thought to
      represent ballistically emplaced ejecta from impacts but the identification of
      source craters and the detailed study of the regolith modification have been
      hampered by the limited spatial resolution and area coverage of the few asteroids
      imaged by spacecraft. Here we report the results of global mapping of the
      asteroid 433 Eros from high-resolution images obtained by the NEAR-Shoemaker
      spacecraft. Based on the images and ejecta-emplacement models, we suggest that
      most large ejecta blocks on Eros originate from a relatively young 7.6-km
      diameter crater. A large fraction of the ejecta from impacts pre-dating that
      crater has apparently been buried or eroded. The images also show evidence for
      the action of a variety of sorting environments for regolith particles after they
      are deposited on the surface.

PMID- 11574881
TI  - The nature of ponded deposits on Eros.
AB  - One of the surprises of the NEAR-Shoemaker mission was that Eros's surface
      exhibits a wide variety of landforms, which are indicative of a global covering
      of loose fragmental debris. At one extreme in roughness is the Shoemaker Regio
      area, which is characterized by a high density of boulders up to 100 m across,
      slumps, slides, and finer blanketing material. At the other extreme are
      distinctive, flat deposits that appear smooth down to a resolution of 1.2 cm per
      pixel. Here we report the results of global mapping and colour analysis of these
      smooth deposits. They have formed most efficiently in restricted areas, and
      appear to be the result of deposition of finer material sorted from the upper
      portion of the asteroid's regolith. The smooth deposits constitute a family of
      features with a range of morphologies, but all appear to be the result of
      sedimentation. The geography of the deposits is consistent with some predicted
      aspects of photoelectric sorting, but these exotic transport and depositional
      mechanisms are not well understood. Deposits with the properties seen on Eros
      have no obvious analogues in previous lunar or asteroid data.

PMID- 11574882
TI  - Experimental long-lived entanglement of two macroscopic objects.
AB  - Entanglement is considered to be one of the most profound features of quantum
      mechanics. An entangled state of a system consisting of two subsystems cannot be
      described as a product of the quantum states of the two subsystems. In this
      sense, the entangled system is considered inseparable and non-local. It is
      generally believed that entanglement is usually manifest in systems consisting of
      a small number of microscopic particles. Here we demonstrate experimentally the
      entanglement of two macroscopic objects, each consisting of a caesium gas sample
      containing about 1012 atoms. Entanglement is generated via interaction of the
      samples with a pulse of light, which performs a non-local Bell measurement on the
      collective spins of the samples. The entangled spin-state can be maintained for
      0.5 milliseconds. Besides being of fundamental interest, we expect the robust and
      long-lived entanglement of material objects demonstrated here to be useful in
      quantum information processing, including teleportation of quantum states of
      matter and quantum memory.

PMID- 11574883
TI  - A Bragg glass phase in the vortex lattice of a type II superconductor.
AB  - Although crystals are usually quite stable, they are sensitive to a disordered
      environment: even an infinitesimal amount of impurities can lead to the
      destruction of crystalline order. The resulting state of matter has been a long
      standing puzzle. Until recently it was believed to be an amorphous state in which
      the crystal would break into 'crystallites'. But a different theory predicts the
      existence of a novel phase of matter: the so-called Bragg glass, which is a glass
      and yet nearly as ordered as a perfect crystal. The 'lattice' of vortices that
      contain magnetic flux in type II superconductors provide a good system to
      investigate these ideas. Here we show that neutron-diffraction data of the vortex
      lattice provides unambiguous evidence for a weak, power-law decay of the
      crystalline order characteristic of a Bragg glass. The theory also predicts
      accurately the electrical transport properties of superconductors; it naturally
      explains the observed phase transitions and the dramatic jumps in the critical
      current associated with the melting of the Bragg glass. Moreover, the model
      explains experiments as diverse as X-ray scattering in disordered liquid crystals
      and the conductivity of electronic crystals.

PMID- 11574884
TI  - The jamming route to the glass state in weakly perturbed granular media.
AB  - It has been suggested that a common conceptual framework known as 'jamming' (refs
      1 and 2) may be used to classify a wide variety of physical systems; these
      include granular media, colloidal suspensions and glass-forming liquids, all of
      which display a critical slowdown in their dynamics before a sudden transition to
      an amorphous rigid state. Decreasing the relevant control parameter (such as
      temperature, drive or inverse density) may cause geometrical constraints to build
      up progressively and thus restrict the accessible part of the system's phase
      space. In glass-forming liquids (thermal molecular systems), jamming is provided
      by the classical vitrification process of supercooling, characterized by a
      rapidly increasing and apparently diverging viscosity at sufficiently low
      temperatures. In driven (athermal) macroscopic systems, a similar slowdown has
      been predicted to occur, notably in sheared foam or vibrated granular media. Here
      we report experimental evidence for dynamic behaviour, qualitatively analogous to
      supercooling, in a driven granular system of macroscopic millimetre-size
      particles. The granular medium is perturbed by isolated tapping or continuous
      vibration, with the perturbation intensity serving as a control parameter. We
      observe the random deflection of an immersed torsion oscillator that moves each
      time the grains rearrange, like a 'thermometer' sensing the granular noise. We
      caution that our granular analogy to supercooling is based on similarities in the
      dynamical behaviour, rather than quantitative theory.

PMID- 11574885
TI  - Photochemical cycling of iron in the surface ocean mediated by microbial
      iron(III)-binding ligands.
AB  - Iron is a limiting nutrient for primary production in large areas of the oceans.
      Dissolved iron(III) in the upper oceans occurs almost entirely in the form of
      complexes with strong organic ligands presumed to be of biological origin.
      Although the importance of organic ligands to aquatic iron cycling is becoming
      clear, the mechanism by which they are involved in this process remains
      uncertain. Here we report observations of photochemical reactions involving
      Fe(III) bound to siderophores--high-affinity iron(III) ligands produced by
      bacteria to facilitate iron acquisition. We show that photolysis of Fe(III)
      siderophore complexes leads to the formation of lower-affinity Fe(III) ligands
      and the reduction of Fe(III), increasing the availability of siderophore-bound
      iron for uptake by planktonic assemblages. These photochemical reactions are
      mediated by the alpha-hydroxy acid moiety, a group which has generally been found
      to be present in the marine siderophores that have been characterized. We suggest
      that Fe(III)-binding ligands can enhance the photolytic production of reactive
      iron species in the euphotic zone and so influence iron availability in aquatic
      systems.

PMID- 11574886
TI  - Earliest presence of humans in northeast Asia.
AB  - The timing of the earliest habitation and oldest stone technologies in different
      regions of the world remains a contentious topic in the study of human evolution.
      Here we contribute to this debate with detailed magnetostratigraphic results on
      two exposed parallel sections of lacustrine sediments at Xiaochangliang in the
      Nihewan Basin, north China; these results place stringent controls on the age of
      Palaeolithic stone artifacts that were originally reported over two decades ago.
      Our palaeomagnetic findings indicate that the artifact layer resides in a reverse
      polarity magnetozone bounded by the Olduvai and Jaramillo subchrons. Coupled with
      an estimated rate of sedimentation, these findings constrain the layer's age to
      roughly 1.36 million years ago. This result represents the age of the oldest
      known stone assemblage comprising recognizable types of Palaeolithic tool in east
      Asia, and the earliest definite occupation in this region as far north as 40
      degrees N.

PMID- 11574887
TI  - Lagged effects of ocean climate change on fulmar population dynamics.
AB  - Environmental variation reflected by the North Atlantic Oscillation affects
      breeding and survival in terrestrial vertebrates, and climate change is predicted
      to have an impact on population dynamics by influencing food quality or
      availability. The North Atlantic Oscillation also affects the abundance of marine
      fish and zooplankton, but it is unclear whether this filters up trophic levels to
      long-lived marine top predators. Here we show by analysis of data from a 50-year
      study of the fulmar that two different indices of ocean climate variation may
      have lagged effects on population dynamics in this procellariiform seabird.
      Annual variability in breeding performance is influenced by the North Atlantic
      Oscillation, whereas cohort differences in recruitment are related to temperature
      changes in the summer growing season in the year of birth. Because fulmars
      exhibit delayed reproduction, there is a 5-year lag in the population's response
      to these effects of environmental change. These data show how interactions
      between different climatic factors result in complex dynamics, and that the
      effects of climate change may take many years to become apparent in long-lived
      marine top predators.

PMID- 11574888
TI  - Histamine regulates T-cell and antibody responses by differential expression of
      H1 and H2 receptors.
AB  - Many pathological processes, including those causing allergies and autoimmune
      diseases, are associated with the presence of specialized subsets of T helper
      cells (TH1 and TH2) at the site of inflammation. The diversity of TH1 and TH2
      function is not predetermined but depends on signals that drive the cells towards
      either subset. Histamine, released from effector cells (mast cells and basophils)
      during inflammatory reactions can influence immune response. Here we report that
      histamine enhances TH1-type responses by triggering the histamine receptor type 1
      (H1R), whereas both TH1- and TH2-type responses are negatively regulated by H2R
      through the activation of different biochemical intracellular signals. In mice,
      deletion of H1R results in suppression of interferon (IFN)-gamma and dominant
      secretion of TH2 cytokines (interleukin (IL)-4 and IL-13). Mutant mice lacking
      H2R showed upregulation of both TH1 and TH2 cytokines. Relevant to T-cell
      cytokine profiles, mice lacking H1R displayed increased specific antibody
      response with increased immunoglobulin-epsilon (IgE) and IgG1, IgG2b and IgG3
      compared with mice lacking H2R. These findings account for an important
      regulatory mechanism in the control of inflammatory functions through effector
      cell-derived histamine.

PMID- 11574889
TI  - Auxin transport inhibitors block PIN1 cycling and vesicle trafficking.
AB  - Polar transport of the phytohormone auxin mediates various processes in plant
      growth and development, such as apical dominance, tropisms, vascular patterning
      and axis formation. This view is based largely on the effects of polar auxin
      transport inhibitors. These compounds disrupt auxin efflux from the cell but
      their mode of action is unknown. It is thought that polar auxin flux is caused by
      the asymmetric distribution of efflux carriers acting at the plasma membrane. The
      polar localization of efflux carrier candidate PIN1 supports this model. Here we
      show that the seemingly static localization of PIN1 results from rapid actin
      dependent cycling between the plasma membrane and endosomal compartments. Auxin
      transport inhibitors block PIN1 cycling and inhibit trafficking of membrane
      proteins that are unrelated to auxin transport. Our data suggest that PIN1
      cycling is of central importance for auxin transport and that auxin transport
      inhibitors affect efflux by generally interfering with membrane-trafficking
      processes. In support of our conclusion, the vesicle-trafficking inhibitor
      brefeldin A mimics physiological effects of auxin transport inhibitors.

PMID- 11574890
TI  - Voltage-induced membrane movement.
AB  - Thermodynamics predicts that transmembrane voltage modulates membrane tension and
      that this will cause movement. The magnitude and polarity of movement is governed
      by cell stiffness and surface potentials. Here we confirm these predictions using
      the atomic force microscope to dynamically follow the movement of voltage-clamped
      HEK293 cells in different ionic-strength solutions. In normal saline,
      depolarization caused an outward movement, and at low ionic strength an inward
      movement. The amplitude was proportional to voltage (about 1 nm per 100 mV) and
      increased with indentation depth. A simple physical model of the membrane and tip
      provided an estimate of the external and internal surface charge densities (-5 x
      10(-3) C x m(-2) and -18 x 10(-3) C x m(-2), respectively). Salicylate (a
      negative amphiphile) inhibited electromotility by increasing the external charge
      density by -15 x 10(-3) C x m(-2). As salicylate blocks electromotility in
      cochlear outer hair cells at the same concentration, the role of prestin as a
      motor protein may need to be reassessed.

PMID- 11574891
TI  - The RNA component of telomerase is mutated in autosomal dominant dyskeratosis
      congenita.
AB  - Dyskeratosis congenita is a progressive bone-marrow failure syndrome that is
      characterized by abnormal skin pigmentation, leukoplakia and nail dystrophy. X
      linked, autosomal recessive and autosomal dominant inheritance have been found in
      different pedigrees. The X-linked form of the disease is due to mutations in the
      gene DKC1 in band 2, sub-band 8 of the long arm of the X chromosome (ref. 3). The
      affected protein, dyskerin, is a nucleolar protein that is found associated with
      the H/ACA class of small nucleolar RNAs and is involved in pseudo-uridylation of
      specific residues of ribosomal RNA. Dyskerin is also associated with telomerase
      RNA (hTR), which contains a H/ACA consensus sequence. Here we map the gene
      responsible for dyskeratosis congenita in a large pedigree with autosomal
      dominant inheritance. Affected members of this family have an 821-base-pair
      deletion on chromosome 3q that removes the 3' 74 bases of hTR. Mutations in hTR
      were found in two other families with autosomal dominant dyskeratosis congenita.

PMID- 11574892
TI  - DNA topoisomerase IIalpha is required for RNA polymerase II transcription on
      chromatin templates.
AB  - In the nucleus of the cell, core RNA polymerase II (pol II) is associated with a
      large complex called the pol II holoenzyme (holo-pol). Transcription by core pol
      II in vitro on nucleosomal templates is repressed compared with that on templates
      of histone-free naked DNA. We found that the transcriptional activity of holo
      pol, in contrast to that of core pol II, is not markedly repressed on chromatin
      templates. We refer to this property of holo-pol as chromatin-dependent
      coactivation (CDC). Here we show that DNA topoisomerase IIalpha is associated
      with the holo-pol and is a required component of CDC. Etoposide and ICRF-193,
      specific inhibitors of topoisomerase II, blocked transcription on chromatin
      templates, but did not affect transcription on naked templates. Addition of
      purified topoisomerase IIalpha reconstituted CDC activity in reactions with core
      pol II. These findings suggest that transcription on chromatin templates results
      in the accumulation of superhelical tension, making the relaxation activity of
      topoisomerase II essential for productive RNA synthesis on nucleosomal DNA.

PMID- 11574894
TI  - Are you part of the Canadian Drug Advertising Self-Regulation System?

PMID- 11574895
TI  - Major depression: prevalence, treatment utilization and age in Canada.
AB  - OBJECTIVE: To determine the relationships between age, prevalence of major
      depression and antidepressant treatment in Canadian populations by using data
      from three health surveys. BACKGROUND: Major depression is an important disorder,
      and there is a concern that treatment for it may be underutilized. Age may have
      an impact on treatment use. METHODS: Two of the surveys incorporated into the
      present analysis were random digit dial telephone surveys, with sample sizes of
      2542 subjects and 796 subjects, respectively. The third data source was the
      National Population Health Survey (n=73,402), which used some face to face and
      some telephone-based data collection methods. In each of these studies, major
      depression was evaluated using a short form version of the Composite
      International Diagnostic Interview for Major Depression. Diagnostic status was
      evaluated in relation to current use of antidepressant medications, age and other
      relevant factors. All analyses accounted for unequal selection probabilities and
      clustering inherent in the sampling procedures. RESULTS: The prevalence of major
      depression was consistently found to be highest in subjects under the age of 45
      years. However, older subjects were more likely to report having depression
      diagnosed. Antidepressant treatment was found to be less frequent in young
      subjects, despite these subjects being in the group with the highest prevalence
      of depression. Younger respondents were less likely to see a physician about
      their depressive symptoms, and when they did they were less likely to be told
      that they had a depressive disorder. CONCLUSIONS: The data presented indicate
      that antidepressant medications tend to be used less frequently in younger than
      older age groups in Canada. Additional studies are needed to confirm optimal use
      rates in relation to age.

PMID- 11574896
TI  - Physician characteristics in relation to cardiovascular drugs commonly prescribed
      for hypertension in Nova Scotia.
AB  - BACKGROUND: Cardiovascular drugs are the most frequently prescribed class of
      drugs in Canada. Among them, drugs used to treat hypertension are the single
      largest component. Variability in how these drugs are prescribed should be based
      on the specific characteristics of patients. However, some evidence shows that
      physician characteristics can also play a substantial role in prescribing trends.
      Such variation is also associated with varying beneficial and adverse patient
      outcomes. PURPOSE: To determine whether prescribing patterns of drugs used to
      treat hypertension in elderly patients in Nova Scotia varied by physician
      characteristics. METHODS: A retrospective, population-based descriptive study was
      done using the Nova Scotia Pharmacare program data for the fiscal year 1995/96.
      The unit of analysis was the individual physician. All drugs indicated in the
      management of hypertension were included for the analysis. RESULTS: Of 1466
      physicians included in the analysis, 1004 were family physicians (FPs) and/or
      general practitioners (GPs), 155 were internal medicine specialists and 307 were
      other specialists. Fifty-eight per cent of 103,193 eligible senior citizens
      received at least one of the study medications. FPs and/or GPs prescribed 95.9%
      of all the study drugs. Internists prescribed proportionately fewer angiotensin
      converting enzyme inhibitors, thiazides and other diuretics compared with the FPs
      and/or GPs but more beta-blockers and calcium channel blockers. A large
      proportion of the FPs and/or GPs (55.3%) prescribed less than 10% of the total
      day's supply of drugs, whereas a small proportion of FPs and/or GPs (16.3%)
      prescribed 52.6% of all the study drugs. There was no variation in the
      distribution of the types of antihypertensives prescribed based on physician age,
      sex or volume of prescribing. A slight variation in prescribing was seen with
      location of practice. CONCLUSIONS: Patterns of prescribing cardiovascular drugs
      used to treat hypertension were remarkably unaffected by physician
      characteristics. This finding counters other evidence in the literature that has
      raised concerns over prescribing patterns of certain types of physicians.
      Prescribing patterns may vary for other drug classes, but for this group of
      antihypertensives, little variability was found.

PMID- 11574897
TI  - Examining the Saskatchewan health drug database for antidepressant use: the case
      of fluoxetine.
AB  - OBJECTIVE: To examine the use of fluoxetine in an adult population in
      Saskatchewan. METHODS: All adults in the Saskatchewan health care databases who
      had begun fluoxetine therapy between January 1992 and June 1996 and had not
      received an antidepressant in the six months before the index fluoxetine
      prescription were identified. Fluoxetine use for the subsequent six-month period
      was examined. The rates of completion of six months of fluoxetine, rates of
      stopping, switching to another serotonin-selective reuptake inhibitor (SSRI) or
      other class of antidepressant, resumption of fluoxetine, as well as average
      dosages taken and mean duration of therapy were determined. Rates were summarized
      as means with standard deviation. RESULTS: Data were obtained for 11,322
      subjects, of whom 68.2% were women; 17.4% were 65 years of age or older. The
      average prescribed daily dose of fluoxetine was 22.5 mg (SD=21.7) and the average
      duration was 88.1 days (SD=57.2). Only 18.9% of patients filled prescriptions for
      six months, 7049 (62.3%) stopped fluoxetine at least once for one month or more,
      and 17.3% were titrated to a higher dose, on average 71 days (SD=44) after the
      initiation of fluoxetine. The proportion of patients switching to another
      antidepressant was 13.6% (3.3% to another SSRI, 10.3% to other classes), after a
      mean of 69 days (SD=51) of fluoxetine treatment. CONCLUSIONS: The authors' data
      suggest that there is a potential underutilization of fluoxetine in the study
      population. Further research may be warranted to determine the proportion of
      depressed patients in this population and to better understand the stop-switch
      resume pattern of antidepressant use.

PMID- 11574898
TI  - In human therapy, is the drug-drug interaction or the adverse drug reaction the
      issue?
AB  - In recent years, many publications in scientific journals have reported, in
      healthy volunteers, potential food-drug or drug-drug interactions. The lay press
      has frequently emphasized such interactions and extrapolated on the dangers of
      food-drug or drug-drug interactions. However, the clinical relevancy of these
      interactions has not always been substantiated in patients. The aim of the
      present review was to assess the clinical relevancy of drug-drug interactions
      occurring at the level of the biotransformation of the drug. For this purpose,
      the incidence of serious, life-threatening adverse drug reactions (ADRs) of drugs
      metabolized by different enzymes of cytochrome P450 found in the safety reports
      issued in megatrials were compared with those from placebo trials. It was
      concluded that serious ADRs secondary to drug-drug interactions are infrequent;
      drug-drug interactions including selected drugs with a narrow therapeutic index
      and eliciting life-threatening undesired effects occur; and serious ADRs
      secondary to drug-drug interactions are most frequent in elderly patients, in the
      presence of polypharmacy, in the psychiatric patient population, and in the
      presence of inappropriate prescriptions and of multiple prescriptors.

PMID- 11574899
TI  - Journal supplements and evidence-based medicine.

PMID- 11574902
TI  - Understanding the neuropsychological syndrome of dementia.
AB  - The syndrome of dementia is most commonly caused by Alzheimer's disease (AD), an
      age-related neurodegenerative process that primarily affects the cortex.
      Approximately 4 million Americans carry the diagnosis, and the number is expected
      to rise to 14 million by the year 2040. Affected individuals suffer multiple
      cognitive deficits that progressively affect the ability to communicate.
      Typically the earliest symptom is impairment of episodic memory, but other forms
      of declarative memory are ultimately impaired. To understand the communication
      problems of individuals with Alzheimer's, clinicians need to understand disease
      effects on knowledge stores and cognitive and memory processes. Using spared
      memory systems and less effortful cognitive processes to compensate for impaired
      stores and processes is the primary means by which optimal care can be provided.
      Recent advances in our understanding of disease effects on semantic memory
      suggest a greater potential for habilitation than previously thought. In this
      article, the neuropathology of AD is reviewed, effects on cognitive and
      communicative functions are specified, and principles for providing optimal
      patient care are discussed.

PMID- 11574903
TI  - Retained neuropsychological abilities of individuals with Alzheimer's disease.
AB  - Individuals with Alzheimer's disease (AD) retain certain cognitive abilities over
      the course of the disease. In this article, we describe retained cognitive
      linguistic abilities and the status of activities of daily living (ADLs) of
      individuals in the early, middle, and late stages of AD. Knowledge of preserved
      abilities in AD is necessary for clinicians to structure communication
      stimulation programs and to train caregivers in the most effective ways to
      facilitate communication. Using the Global Deterioration Scale (GDS) for staging
      severity of AD, an outline of preserved abilities by disease stage is provided.
      Attention, memory, and communication abilities are discussed, and samples of
      discourse from patients at different stages are included.

PMID- 11574904
TI  - Comprehensive assessment for dementia: a necessity for differential diagnosis and
      management.
AB  - A fundamental purpose of comprehensive assessment is to identify impaired and
      spared abilities of the individual with Alzheimer's disease (AD). In the hands of
      a skilled professional, the results of a comprehensive assessment provide the
      basis for the design of meaningful care plans, document the need for appropriate
      services, and result in optimal patient care. To obtain valid test results,
      clinicians must be able to recognize and, when possible, control the influence of
      age-associated variables on test performance. Also, clinicians must be
      knowledgeable about the many purposes of assessment and consider them when
      selecting appropriate test instruments. Standardized tests are now available that
      have been designed specifically to assess communicative and cognitive function in
      persons with dementia of varying severity. In this article, four standardized
      tests are described, with particular focus on the information they provide about
      impaired and spared abilities. Measures that have been found to be useful in
      screening for the presence of dementia also are discussed.

PMID- 11574905
TI  - Direct interventions for improving the performance of individuals with
      Alzheimer's disease.
AB  - Direct interventions are being used increasingly to maintain and improve the
      communicative and cognitive functioning of patients with Alzheimer's dementia.
      Speech-language pathologists can play an integral role in maximizing the
      functioning of dementia patients by selecting appropriate direct interventions
      that capitalize on spared neuropsychological abilities to compensate for impaired
      abilities. Successful direct interventions use techniques that facilitate
      learning and retention of information and skills. In this article, direct
      intervention techniques-repeated exposure via spaced retrieval training and
      quizzes; errorless learning; multisensory stimulation using music, toys, pets,
      and memory wallets; and other approaches to cognitive-linguistic stimulation such
      as the use of personal computers; the Montessori method; and activity programming
      are reviewed. The rationale for use of these direct interventions and available
      efficacy data with Alzheimer's patients also are presented.

PMID- 11574906
TI  - Indirect interventions to facilitate communication in Alzheimer's disease.
AB  - Indirect interventions are designed to maximize the functioning of individuals
      with Alzheimer's disease (AD) through training of caregivers, modifying the
      physical environment, and developing therapeutic routines and activities. In this
      article, characteristics of AD caregivers are described, caregiver communication
      strategies are discussed, and examples of caregiver communication training
      programs are provided. Environmental modifications and routines and activities to
      improve communication are detailed.

PMID- 11574908
TI  - Transcriptional regulation of major histocompatibility complex class I by
      flavivirus West Nile is dependent on NF-kappaB activation.
AB  - Infection by the flavivirus West Nile (WNV) is associated with a virus-specific
      increase of major histocompatibility complex class I (MHC-I) molecules on the
      cell surface of diploid vertebrate cells. The increased MHC-I cell surface
      expression is functional and is associated with increased susceptibility to
      secondary WNV-immune and alloimmune cytotoxic T cells. WNV-induced up-regulation
      of cell surface MHC-I expression is associated with NF-kappaB activation and
      increased transcription of MHC-I mRNA. WNV infection increases luciferase
      activity of RAWa4 long terminal repeat (LTR) cells, which are transfected stably
      with a plasmid containing 2 NF-kappaB binding sites, the human immunodeficiency
      virus LTR linked to a luciferase reporter gene. The NF-kappaB-induced complexes
      are a p50/p65 heterodimer and another faster migrating species containing p50
      homodimers. WNV-induced activation of NF-kappaB and the up-regulation of MHC-I
      were blocked by the protein kinase C inhibitor H-7 and salicylate, both of which
      block phosphorylation of inhibitor kappaB.

PMID- 11574907
TI  - Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a
      new form of oculocutaneous albinism, OCA4.
AB  - Oculocutaneous albinism (OCA) affects approximately 1/20,000 people worldwide.
      All forms of OCA exhibit generalized hypopigmentation. Reduced pigmentation
      during eye development results in misrouting of the optic nerves, nystagmus,
      alternating strabismus, and reduced visual acuity. Loss of pigmentation in the
      skin leads to an increased risk for skin cancer. Two common forms and one
      infrequent form of OCA have been described. OCA1 (MIM 203100) is associated with
      mutations of the TYR gene encoding tyrosinase (the rate-limiting enzyme in the
      production of melanin pigment) and accounts for approximately 40% of OCA
      worldwide. OCA2 (MIM 203200), the most common form of OCA, is associated with
      mutations of the P gene and accounts for approximately 50% of OCA worldwide. OCA3
      (MIM 203290), a rare form of OCA and also known as "rufous/red albinism," is
      associated with mutations in TYRP1 (encoding tyrosinase-related protein 1).
      Analysis of the TYR and P genes in patients with OCA suggests that other genes
      may be associated with OCA. We have identified the mouse underwhite gene (uw) and
      its human orthologue, which underlies a new form of human OCA, termed "OCA4." The
      encoded protein, MATP (for "membrane-associated transporter protein") is
      predicted to span the membrane 12 times and likely functions as a transporter.

PMID- 11574909
TI  - Cytomegalovirus-specific cellular immune responses and viremia in recipients of
      allogeneic stem cell transplants.
AB  - The immune suppression inherent in allogeneic stem cell transplantation (SCT)
      offers a favorable environment for infection by opportunistic agents, such as
      human cytomegalovirus (CMV). Despite the application of potent antiviral
      prophylaxis, patients remain at risk for CMV infection until adequate immunity is
      restored. CMV-specific CD8(+) T cell counts were monitored, using HLA-A2
      tetrameric complexes, to establish the level of immune response to the viral
      phosphoprotein UL83 in patients after allogeneic SCT. Correlating this with viral
      replication and clinical status shows that the level of tetramer-positive T cells
      provides an assessment of CMV immune reconstitution after stem cell
      transplantation. Most patients with seropositive donors did reconstitute long
      term CMV immunity, unless prolonged immunosuppression to control graft-versus
      host disease was induced. Together with polymerase chain reaction testing, this
      technique provides measurable parameters that can be a guide to therapeutic
      decision making and can form the basis of CMV immunotherapy.

PMID- 11574910
TI  - Early intervention with high-dose acyclovir treatment during primary herpes
      simplex virus infection reduces latency and subsequent reactivation in the
      nervous system in vivo.
AB  - There remains a lack of agreement on the effect of antiviral therapy on herpes
      simplex virus (HSV) latency and subsequent reactivation. To gain insight into
      this important issue, a single-cell polymerase chain reaction assay was used to
      quantify the effects of high-dose acyclovir on latent infection in a mouse model.
      Treatment with 50 mg/kg of acyclovir every 8 h reduced the number of latently
      infected neurons by >90% when treatment was begun before 24 h after infection and
      by 80% and 70% when begun at 48 or 72 h after infection, respectively. The
      biologic significance of these reductions was evaluated by using a well
      established in vivo reactivation model. The number of animals in which virus
      reactivated was reduced significantly, even when acyclovir therapy was delayed
      until 72 h after infection, a time when animals had developed lesions. These
      findings indicate that potent antiviral therapy during early primary HSV
      infection can reduce the magnitude of the latent infection, such that a
      significant decrease in reactivation is observed.

PMID- 11574911
TI  - Specific cellular immune response and cytokine patterns in patients coinfected
      with hepatitis C virus and Schistosoma mansoni.
AB  - Patients coinfected with hepatitis C virus (HCV) and Schistosoma mansoni show
      high incidence of viral persistence and accelerated fibrosis. To determine
      whether immunological mechanisms are responsible for this alteration in the
      natural history of HCV, the HCV-specific peripheral CD4(+) T cell responses and
      cytokines were analyzed in patients with chronic hepatitis C monoinfection, S.
      mansoni monoinfection, or HCV and S. mansoni coinfection. An HCV-specific CD4(+)
      proliferative response to at least 1 HCV antigen was detected in 73.3% of
      patients infected with HCV, compared with 8.6% of patients coinfected with HCV
      and S. mansoni. Stimulation with HCV antigens produced a type 1 cytokine profile
      in patients infected with HCV alone, compared with a type 2 predominance in
      patients coinfected with HCV and S. mansoni. In contrast, there was no difference
      in response to schistosomal antigens in patients infected with S. mansoni alone,
      compared with those coinfected with HCV and S. mansoni. These findings suggest
      that the inability to generate an HCV-specific CD4(+)/Th1 T cell response plays a
      role in the persistence and severity of HCV infection in patients with S. mansoni
      coinfection.

PMID- 11574912
TI  - Secondary mutations in the protease region of human immunodeficiency virus and
      virologic failure in drug-naive patients treated with protease inhibitor-based
      therapy.
AB  - The role of mutations in protease (PR) and reverse-transcriptase (RT) of human
      immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248
      antiretroviral-naive HIV-positive patients who began a PR inhibitor-containing
      antiretroviral regimen. Genotypic testing was performed on plasma samples stored
      before the start of therapy. Twenty-seven patients (10.9%) had mutations in the
      RT, 5 (2%) carried primary mutations in the PR, and 131 (52.8%) showed only
      secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of
      248 patients. There was a statistically significant correlation between virologic
      failure and the number of PR mutations (P= .04, chi(2) test). Mutations at codons
      10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed,
      respectively) were identified by stepwise logistic regression as the strongest
      predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30
      3.75; P= .004). If confirmed in independent studies, this result may justify the
      increased use of HIV genotyping in drug-naive patients requiring antiretroviral
      therapy.

PMID- 11574913
TI  - Trimethoprim-sulfamethoxazole (TMP-SMZ) dose escalation versus direct rechallenge
      for Pneumocystis Carinii pneumonia prophylaxis in human immunodeficiency virus
      infected patients with previous adverse reaction to TMP-SMZ.
AB  - Trimethoprim-sulfamethoxazole (TMP-SMZ) is the most effective Pneumocystis
      carinii pneumonia (PCP) prophylactic agent, but adverse reactions are common
      among human immunodeficiency virus (HIV)-infected patients and limit its use.
      This randomized, double-blind controlled trial compared 2 methods of TMP-SMZ
      reintroduction, 6-day dose escalation and direct rechallenge, for PCP prophylaxis
      in HIV-infected patients who had experienced previous treatment-limiting
      reactions. The primary end point was the ability to take single-strength TMP-SMZ
      daily for 6 months. Seventy-five percent of the dose-escalation group and 57% of
      the direct-rechallenge group continued to receive daily single-strength TMP-SMZ
      for 6 months (P= .014). Among premature discontinuations, 58% of the dose
      escalation group and 70% of the direct-rechallenge group were due to adverse
      reactions. None of these reactions was serious. This study provides evidence that
      it is possible to successfully reintroduce TMP-SMZ to a significant proportion of
      HIV-infected patients who have experienced mild-to-moderate treatment-limiting
      adverse reactions.

PMID- 11574914
TI  - Human immunodeficiency virus type 1 reverse-transcriptase and protease subtypes:
      classification, amino acid mutation patterns, and prevalence in a northern
      California clinic-based population.
AB  - Phylogenetic analysis of the reverse transcriptase (RT) and protease of 117
      published complete human immunodeficiency virus (HIV) type 1 genome sequences
      demonstrated that these genes cluster into distinct subtypes. There was a
      slightly higher proportion of informative sites in the RT (40.4%) than in the
      protease (34.8%; P= .03). Although most variation between subtypes was due to
      synonymous nucleotide substitutions, several subtype-specific amino acid patterns
      were observed. In the protease, the subtype-specific variants included 7
      positions associated with drug resistance. Variants at positions 10, 20, 36, and
      82 were more common in non-B isolates, whereas variants at positions 63, 77, and
      93 were more common in subtype B isolates. In the RT, the subtype-specific
      mutations did not include positions associated with anti-retroviral drug
      resistance. RT and protease sequences from 2246 HIV-infected persons in northern
      California were also examined: 99.4% of the sequences clustered with subtype B,
      whereas 0.6% clustered with subtype A, C, or D.

PMID- 11574915
TI  - Early immunologic events in mucosal and systemic lymphoid tissues after
      intrarectal inoculation with simian immunodeficiency virus.
AB  - The pathogenesis of human immunodeficiency virus transmission via the rectal
      route remains poorly understood. By use of the simian immunodeficiency virus
      (SIV)-rhesus macaque model and intrarectal inoculation with pathogenic SIVmac251,
      a significant increase was found in the percentage of CD11b(+) monocyte lineage
      cells expressing HLA-DR and/or B7-2 in local and peripheral immune inductive
      sites, but not in mucosal effector sites, as early as 7 days after inoculation
      and up to 50 days after inoculation. Moreover, at 21 and 50 days after
      inoculation, not only the gut but also the lung mucosa were depleted of CD4(+) T
      cells, which suggests that early loss of CD4(+) T cells may be a common feature
      of mucosal effector sites. These data suggest that, after intrarectal inoculation
      with SIV, early activation occurs within the monocyte lineage cell population at
      immunologic inductive sites, which is followed by a loss of CD4(+) T cells at
      local and distant mucosal effector sites.

PMID- 11574916
TI  - Increased macrophage chemoattractant protein-1 in cerebrospinal fluid precedes
      and predicts simian immunodeficiency virus encephalitis.
AB  - Macrophage chemoattractant protein-1 (MCP-1) may be a key trigger for the influx
      of macrophages into the brain in human immunodeficiency virus (HIV) encephalitis.
      In this study, simian immunodeficiency virus-infected macaques that developed
      moderate-to-severe encephalitis had significantly higher MCP-1 levels in
      cerebrospinal fluid (CSF) than in plasma as early as 28 days after inoculation,
      which was before the development of brain lesions. In contrast, CSF:plasma MCP-1
      ratios remained constant at preinoculation levels in macaques that developed
      minimal or no encephalitis. Abundant MCP-1 protein and mRNA were detected in both
      macrophages and astrocytes in the brain. Macaques with increased MCP-1 in CSF had
      significantly greater expression of markers of macrophage and microglia
      activation and infiltration (CD68; P= .003) and astrocyte activation (glial
      fibrillary acidic protein; P= .019 and P= .031 in white and gray matter,
      respectively). The results suggest that the CSF:plasma MCP-1 ratio may be a
      valuable prognostic marker for the development of HIV-induced central nervous
      system disease.

PMID- 11574917
TI  - Level of maternal antibody required to protect neonates against early-onset
      disease caused by group B Streptococcus type Ia: a multicenter, seroepidemiology
      study.
AB  - Because of the difficulty of conducting efficacy trials of vaccines against group
      B streptococcus (GBS), the licensure of these vaccines may have to rely on
      studies that measure vaccine-induced antibody levels that correlate with
      protection. This study estimates the level of maternal antibody required to
      protect neonates against early-onset disease (EOD) caused by GBS type Ia. Levels
      of maternal serum IgG GBS Ia antibodies, measured by ELISAs in 45 case patients
      (neonates with EOD caused by GBS Ia) and in 319 control subjects (neonates
      colonized by GBS Ia but without EOD) born at > or =34 weeks gestation were
      compared. The probability of developing EOD declined with increasing maternal
      levels of IgG GBS Ia antibody (P = .03). Neonates whose mothers had levels of IgG
      GBS Ia antibody > or =5 microg/mL had an 88% lower risk (95% confidence interval,
      7%-98%) of developing type-specific EOD, compared with those whose mothers had
      levels < 0.5 microg/mL. A vaccine that induces IgG GBS Ia antibody levels > or =5
      microg/mL in mothers can be predicted to confer a high degree of type-specific
      immunity to EOD to their infants.

PMID- 11574918
TI  - Population-based incidence and characteristics of community-onset Staphylococcus
      aureus infections with bacteremia in 4 metropolitan Connecticut areas, 1998.
AB  - This study retrospectively analyzed the magnitude and epidemiology of community
      onset Staphylococcus aureus (COSA) infections and methicillin-resistant S. aureus
      (MRSA) infections in 4 Connecticut metropolitan areas (population, 1.1 million).
      The study looked at hospital medical records of persons admitted with S. aureus
      bacteremia in 1998. COSA was categorized as "health care associated," "with
      underlying medical condition," or "no underlying medical condition." Overall, 48%
      of S. aureus bacteremic infections were COSA (incidence, 17 cases/100,000
      persons). Incidence increased with age and higher population density. In all, 62%
      of infections were health care associated; 85% of the remaining cases had
      underlying medical conditions. MRSA accounted for 16% of health care-associated
      cases and cases with underlying conditions but no cases with no underlying
      conditions. COSA bacteremic infections are as common as those due to pneumococci.
      MRSA is a well-established cause of COSA among persons at high medical risk for
      S. aureus infection. Additional study to understand community-onset MRSA
      acquisition is needed.

PMID- 11574919
TI  - Diphtheria in Thailand in the 1990s.
AB  - Diphtheria remains endemic in developing countries, but there are limited
      published data on the subject. Thailand's diphtheria surveillance data are
      relatively complete and may give a fuller picture of the situation in similar
      countries. After routine immunization began in 1977, the incidence of reported
      diphtheria decreased by >98% to <0.1 case per 100,000 persons annually in the
      1990s. Despite infant immunization coverage of >90%, diphtheria cases were
      reported throughout the 1990s, primarily among children <15 years old. Outbreaks
      were linked to both persistent endemic circulation and to importation of
      toxigenic Corynebacterium diphtheriae; suboptimal immunization coverage in
      minority and disadvantaged groups contributed. A serologic survey found 25% of
      adults 20-39 years old and 14% of adolescents 10-19 years old lacked immunity to
      diphtheria; these data indicate an accumulation of susceptible adolescents and
      adults. Diphtheria remains a threat in Thailand; improvements in diphtheria
      control will depend on improving childhood immunization coverage in Thailand and
      the surrounding region.

PMID- 11574920
TI  - Identification of DNA sequences from a second pathogenicity island of
      uropathogenic Escherichia coli CFT073: probes specific for uropathogenic
      populations.
AB  - Uropathogenic Escherichia coli is the leading cause of urinary tract infection
      and hospital visits in North America. Cystitis and acute pyelonephritis,
      infection of the bladder and kidney, respectively, are the two most common
      syndromes encountered in patients with urinary tract infection. We sequenced and
      annotated 71,684 bases of a previously unidentified pathogenicity-associated
      island (PAI) from E. coli strain CFT073. This PAI contained 89 open-reading
      frames encoding a pap operon, iron-regulated genes, mobile genetic elements, and
      a large proportion of unknown or unidentified open-reading frames. Dot blot
      analysis with 11 DNA sequences from this PAI demonstrated that 7 sequences were
      more prevalent among uropathogens: 2 probes were more prevalent among cystitis
      and pyelonephritis isolates, 2 among pyelonephritis isolates only, and 3 among
      cystitis isolates only than among fecal isolates. These data suggest that groups
      of uropathogens have genetic differences that may be responsible for the
      different clinical outcomes.

PMID- 11574921
TI  - A large outbreak of foodborne infection attributed to Providencia alcalifaciens.
AB  - The enteropathogenicity of Providencia alcalifaciens, a member of the family
      Enterobacteriaceae, has not yet been well established. In November 1996, a large
      outbreak of foodborne infection occurred in Fukui, Japan. In this study, the
      etiology of the outbreak was investigated. No other recognized enteropathogens
      were detected in patient fecal samples, but P. alcalifaciens was detected in 7 of
      18 samples. The isolates were found to be clonal by pulsed-field gel
      electrophoresis. The patients who presented with gastroenteritis had elevated
      levels of specific antibody against the isolated P. alcalifaciens. The isolates
      showed invasion of Caco-2 cells and fluid accumulation in rabbit ileal loops.
      This study strongly suggests that the outbreak was caused by P. alcalifaciens.
      This is the first report of a large outbreak of foodborne infection attributed to
      the organism and provides definitive evidence that P. alcalifaciens is a
      causative agent of gastroenteritis.

PMID- 11574922
TI  - Salp25D, an Ixodes scapularis antioxidant, is 1 of 14 immunodominant antigens in
      engorged tick salivary glands.
AB  - Rabbits or guinea pigs infested with Ixodes scapularis acquire resistance to tick
      bites, a phenomenon, known as tick immunity, that is partially mediated by
      antibody. To determine the salivary gland antigens that elicit antibodies in the
      host, an I. scapularis salivary gland cDNA expression library was probed with
      serum from tick-immune rabbits. Sera from sensitized rabbits strongly recognized
      47 of 100,000 library clones in an antibody-screening assay. These 47 clones
      encoded 14 different I. scapularis genes, including a glutathione peroxidase
      homologue. Expression of these 14 genes in engorged tick salivary glands was
      confirmed by reverse-transcription polymerase chain reaction. The I. scapularis
      glutathione peroxidase homologue, named salp25D, was expressed in both unfed and
      fed nymphal salivary glands. Recombinant Salp25D was able to catalyze the
      reduction of hydrogen peroxide in the presence of reduced glutathione and
      glutathione reductase. These results categorize the prominent salivary gland
      proteins in I. scapularis and demonstrate the presence of a potent antioxidant in
      tick saliva.

PMID- 11574923
TI  - Role of Candida in antibiotic-associated diarrhea.
AB  - To quantitatively assess the role of Candida species in antibiotic-associated
      diarrhea (AAD), stool samples from a total of 395 patients and control subjects
      were cultured in differential isolation medium: 98 patients had AAD, 93 patients
      were taking antibiotics but did not have diarrhea (A(+)D(-)), 97 patients were
      not taking antibiotics but had diarrhea (A(-)D(+)), and 107 patients were control
      subjects (A(-)D(-)). In addition, secreted aspartyl proteinase (Sap) production
      was tested. In AAD patients, Candida positivity (77/98) and Candida overgrowth
      (62/98) were not different from that among A(+)D(-) patients (75/93 [P= .860] and
      52/93 [P= .375], respectively). Candida overgrowth among A(-)D(+) patients
      (40/97, P= .003) was less frequent than among AAD patients, but Candida
      positivity was not different (80/97, P= .612). In control subjects, Candida
      positivity and overgrowth were less common than in all other groups. Production
      of Sap did not differ between patients with AAD and control subjects (P= .568 and
      P= .590, respectively). Data indicate that elevated Candida counts are a result
      of antibiotic treatment or diarrhea rather than a cause of AAD.

PMID- 11574924
TI  - Yield of large-volume blood cultures in patients with early Lyme disease.
AB  - To improve yield, 6 3-mL plasma cultures (18 mL total) were established for adult
      patients with early Lyme disease associated with erythema migrans. Borrelia
      burgdorferi was recovered from the blood of 22 (44.0%) of 50 evaluable patients.
      The recovery rate per plasma culture and the frequency of positive results for
      plasma cultures for individual patients were consistent with a level of
      spirochetemia of approximately 0.1 cultivable cell/mL of whole blood. Our
      findings suggest that, if further improvements in the yield of blood cultures are
      possible, they probably will depend on enhancing the sensitivity of the culture
      method rather than increasing the volume of material cultured.

PMID- 11574925
TI  - Plasma bioavailable interleukin-6 is elevated in human immunodeficiency virus
      infected patients who experience herpesvirus-associated immune restoration
      disease after start of highly active antiretroviral therapy.
AB  - This study compared plasma bioavailable interleukin (IL)-6 levels in 3 groups:
      human immunodeficiency virus (HIV)-infected patients who had a human herpesvirus
      (HHV)-associated immune restoration disease (IRD) during highly active
      antiretroviral therapy (HAART); patients who experienced an IRD initiated by
      Mycobacterium avium complex, hepatitis C virus, or human papillomavirus; and
      control patients who had uneventful immune reconstitution. Total IL-6, soluble IL
      6 receptor (sIL-6R), and soluble gp130 were measured by ELISA, and levels of free
      IL-6 and sIL-6/IL-6R complex were modeled mathematically. Persons who had an HHV
      associated IRD had increased plasma bioavailable IL-6 before HAART, compared with
      patients who experienced a non-HHV-associated IRD and with control patients, and
      their plasma bioavailable IL-6 increased progressively over 3-4 years of
      treatment. Increased IL-6 production may be a feature of HAART-induced
      restoration of immune responses to HHV infections and may have long-term
      immunopathologic consequences.

PMID- 11574926
TI  - Human cytomegalovirus immediate-early messenger RNA in blood of pregnant women
      with primary infection and of congenitally infected newborns.
AB  - Human cytomegalovirus (HCMV) immediate-early messenger RNA (IEmRNA) in sequential
      blood samples from 32 pregnant women with primary infection and from 14
      congenitally infected newborns was qualitatively investigated by nucleic acid
      sequence-based amplification. IEmRNA was detected in 100%, 75%, 36.3%, 22.2%, and
      0% of samples collected 1, 2, 3, 4-6, and >6 months after onset of primary HCMV
      infection, respectively, showing 83.7% sensitivity and 92.2% specificity,
      compared with results of quantitative DNAemia (detection of viral DNA in blood).
      In infected newborns, IEmRNA was positive in 100% of samples collected 1-7 days
      (median, 1.5 days) and in 46.4% of samples collected 27-260 days (median, 88
      days) after birth, showing 75.7% sensitivity and 100% specificity, compared with
      DNAemia results. IEmRNA was not detected in HCMV-immune individuals with remote
      or recurrent HCMV infection or in uninfected newborns. IEmRNA determination
      appears to be a valuable tool for early diagnosis of both primary and congenital
      HCMV infection.

PMID- 11574927
TI  - Granulysin-dependent killing of intracellular and extracellular Mycobacterium
      tuberculosis by Vgamma9/Vdelta2 T lymphocytes.
AB  - Contribution of Vgamma9/Vdelta2 T lymphocytes to immune protection against
      Mycobacterium tuberculosis is still a matter of debate. It was reported earlier
      that Vgamma9/Vdelta2 T lymphocytes kill macrophages harboring live M.
      tuberculosis through a granule-dependent mechanism that results in killing of
      intracellular bacilli. This study found that Vgamma9/Vdelta2 T lymphocytes reduce
      the viability of both extracellular and intracellular M. tuberculosis. Granulysin
      and perforin, both detected in Vgamma9/Vdelta2 T lymphocytes, play a major role,
      which indicates that Vgamma9/Vdelta2 T lymphocytes directly contribute to a
      protective host response against M. tuberculosis infection.

PMID- 11574928
TI  - Nitric oxide and cytokine synthesis in human African trypanosomiasis.
AB  - Plasma and cerebrospinal fluid (CSF) concentrations of nitrate and the cytokines
      interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-10,
      and IL-4 were measured in 91 African trypanosomiasis patients before and after
      treatment. Nitrate levels overall were not significantly elevated over those for
      control persons, but a marginal increase in plasma nitrate was detected in
      patients reporting illness of <40 days' duration. Plasma IFN-gamma and total TNF
      alpha concentrations increased during infection, but free TNF-alpha levels were
      low in all patients. The most dramatic cytokine response was for IL-10, which was
      significantly elevated in both plasma and CSF during infection but returned to
      control levels after treatment. The results indicate that human African
      trypanosomiasis leads to the development of a strong anti-inflammatory cytokine
      response.

PMID- 11574929
TI  - Procalcitonin levels in severe Plasmodium falciparum malaria: predictor of
      outcome or reflection of pathomechanisms?

PMID- 11574931
TI  - A comparison of normal and leukemic stem cell biology in Chronic Myeloid
      Leukemia.
AB  - Chronic Myeloid Leukemia (CML), a myeloproliferative disease of stem cell origin,
      is characterized by the presence of the Philadelphia (Ph) chromosome and the bcr
      abl oncogene. The BCR-ABL fusion gene product, thought to be causative in CML,
      has multiple effects on diverse cell functions such as growth, differentiation
      and turnover as well as adhesion and apoptosis. Persistent Ph-negative
      progenitors co-exist with leukemic cells, both in the marrow and blood of
      patients, in the early chronic phase of the disease. Despite accumulating
      knowledge of hemopoiesis and the disease process, CML remains incurable with
      conventional chemotherapy. Nonetheless, with the efficacy of the ABL tyrosine
      kinase inhibitor STI-571 (signal transduction inhibitor 571) as a novel therapy
      in CML recently being realized in clinical trials, it is therefore timely to
      review our current understanding of the cell biology of this fascinating disease.

PMID- 11574932
TI  - Recent advances in the treatment of AML.

PMID- 11574933
TI  - Recent publications in hematological oncology.

PMID- 11574934
TI  - When life begins ...

PMID- 11574935
TI  - Interactions between prostate volume, filling cystometric estimated parameters,
      and data from pressure-flow studies in 565 men with lower urinary tract symptoms
      suggestive of benign prostatic hyperplasia.
AB  - The aim of this study was to establish the characteristics and to investigate the
      interactions between prostate volume, degree of obstruction, bladder
      contractility, the prevalence of residual volume, bladder compliance, bladder
      capacities, and the prevalence of instability in a large, well-defined group of
      men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic
      hyperplasia (BPH). The 565 consecutive men included in this study met the
      criteria of the International Consensus Committee on BPH and voided more than 150
      mL during uroflowmetry. Their residual urine volume and prostate size were
      estimated, and filling cystometry and pressure-flow studies were performed. Fifty
      three percent of the men appeared to have obstruction. We found a positive
      correlation between prostate volume and Schafer's obstruction grade, except that
      mean prostate volume decreased at Schafer's grades 5 and 6. Significant negative
      correlations existed between Schafer's grade and cystometric bladder capacity and
      effective capacity. Bladder outlet obstruction results in incomplete emptying. Of
      all men, 26% had a significant residual volume ( > 20% of cystometric capacity).
      Thirty-nine percent did not have residual volume. Of the 565 men, 46% had an
      unstable bladder. In particular, patients with an unstable bladder in the sitting
      and lying positions have a significantly higher Schafer's grade and contractility
      grade and a significantly lower cystometric and effective bladder capacity
      compared with patients without instability. Patients with a residual volume or
      instability were significantly older. We conclude that in men with LUTS
      suggestive of BPH, abnormalities of bladder and bladder outlet function vary
      greatly and have complex mutual interactions.

PMID- 11574936
TI  - Effectiveness of two conservative modes of physical therapy in women with urinary
      stress incontinence.
AB  - Stress incontinence is the most prevalent form of female urinary incontinence and
      it affects approximately 5% of younger women to nearly 50% of elderly women.
      Women have traditionally been treated with pelvic floor muscle exercises alone or
      with the use of vaginal cones. A new treatment mode, vaginal balls, has been
      developed. The aim of this study was to compare pelvic floor muscle training with
      and without vaginal balls and to collect information on women's subjective
      feelings about the two training modes. The study was carried out as a prospective
      randomized clinical trial. Thirty-seven women aged 25-65 were assigned either to
      a pelvic floor muscle training program or to a training program using weighted
      vaginal balls for 4 months. Treatment outcomes were assessed by a pad-test with a
      standardized bladder volume, vaginal palpation, and by women's self-reported
      perceptions. The sense of coherence score was compared with the score for a
      normal population. Ninety-three percent of the women completed the study. Both
      training modes were effective in reducing urinary leakage: with vaginal balls (P
      < 0.0001) and without (P < 0.019); and increasing pelvic floor muscle strength:
      with vaginal balls (P < 0.0039) and without (P < 0.0002). However, the reduction
      of urinary leakage after four months of exercise in the training group with
      vaginal balls was significantly better (P < 0.03) than the results in the group
      training with pelvic floor muscle exercises alone. The study found the weighted
      vaginal balls to be a good alternative for training pelvic floor muscles in women
      with stress urinary incontinence.

PMID- 11574937
TI  - Characterisation of lower urinary tract disorders: a new view.

PMID- 11574939
TI  - Bladder response to urethral flow in the awake ewe.
AB  - The flowing of fluid along the urethra can facilitate the bladder micturition
      contraction, a reflex appropriate to achieve complete bladder emptying. The
      response has been observed in animals studied in the decerebrate, spinal, or
      anesthetized intact state but is difficult to demonstrate in awake, healthy
      humans. The aim of this study was to investigate this reflex in the awake, intact
      state using urodynamics in the ewe. The animals were fully awake and lay gently
      restrained on a recording table. The bladder was catheterized, and urethral flows
      were obtained by slowly injecting saline at the level of the proximal urethra.
      Bladder and rectal pressure were monitored, and the responses to urethral flow
      were tested at various bladder volumes. Urethral flows consistently evoked
      detrusor contractions in all animals. The response started approximately 2
      seconds after the beginning of the flow and largely outlasted the stimulus. Its
      amplitude was similar to that of the bladder-to-bladder micturition reflex, and,
      like the latter, it always required some degree of bladder filling to appear. The
      reflex was selectively suppressed by local anesthesia of the urethral mucosa,
      indicating that the effect must originate from urethral receptors. Small urethral
      flows thus appear to elicit large bladder micturition contractions in awake
      healthy animals, and the reflex could be quite significant during the normal
      micturition. That this reflex is found in all studied species further supports
      the notion that the negative results in normal awake humans are owing to
      descending inhibitory controls rather than to the lack of appropriate pathways.

PMID- 11574938
TI  - Effects of the atypical neuroleptic clozapine on micturition parameters in
      anesthetized rats.
AB  - Clozapine, an atypical antipsychotic, has resulted in a number of reports of
      urinary disturbances in the clinical literature. We examined the effects of
      clozapine on urodynamic parameters in the anesthetized rat and compared the
      effects to those of the typical antipsychotic haloperidol and the selective D2
      and D4 antagonists, raclopride and L-745,870, respectively. Clozapine abolished
      high-frequency oscillations (HFO) during the expulsion phase, and profoundly
      altered a number of other parameters (e.g., intercontraction interval and resting
      pressure). Clozapine did not affect the peak contraction pressure during
      cystometrograms but displayed peripheral inhibition of bladder contractions
      elicited by electrical stimulation of the pelvic nerve (possibly mediated via
      clozapine's anti-muscarinic effects). Haloperidol had less potent effects than
      clozapine since it reduced the amplitude of HFO to 25% of control and also
      affected several other parameters but without peripheral bladder inhibition.
      Raclopride only resulted in a modest decrease (approximately 70% of control) in
      the HFO and no alteration in other parameters. L-745,870 was effective only at
      highest dose tested suggesting that it might not be acting selectively at D4
      receptors. Therefore, we propose that clozapine primarily interferes with the
      function of the external urethral sphincter. These effects can only be partly
      explained through antagonism of D2 receptors. Since both clozapine and
      haloperidol have interactions with other transmitter systems beside dopamine, we
      suggest that central antagonism of D2 receptors, coupled to central antagonism of
      another receptor system and peripheral muscarinic receptor blockade, may account
      for clozapine's potent effects on micturition.

PMID- 11574942
TI  - Terminal effects of ethanol on dopamine dynamics in rat nucleus accumbens: an in
      vitro voltammetric study.
AB  - To assess the direct effects of acute ethanol on dopamine (DA) terminals, evoked
      DA release and uptake were measured in rat nucleus accumbens slices using fast
      scan cyclic voltammetry. Low and moderate concentrations of ethanol (20, 45 and
      100 mM) did not alter evoked DA release, while high concentrations (150 and 200
      mM) significantly decreased DA release (18 and 36%, respectively) in a calcium
      dependent manner. No significant difference was found between the rate of DA
      disappearance measured before and after the drug. These data indicate that uptake
      of DA through the dopamine transporter is unaffected by ethanol, even at high
      concentrations. Therefore, low to moderate concentrations of ethanol have no
      effect on DA dynamics at the level of the nerve terminal in the nucleus
      accumbens. This is consistent with the hypothesis that cell body regions of DA
      neurons are the primary target for the stimulating and reinforcing effects of
      ethanol. High concentrations of ethanol can locally depress DA release, and this
      may correlate with the sedative actions of the drug.

PMID- 11574941
TI  - Acute and chronic caffeine administration differentially alters striatal gene
      expression in wild-type and adenosine A(2A) receptor-deficient mice.
AB  - In order to assess for the respective involvement of adenosine A(1) and A(2A)
      receptors (A(2A)-R) in the consequences of short- and long-term caffeine exposure
      on gene expression, the effects of acute caffeine administration on striatal,
      cortical, and hippocampal expression of immediate early genes (IEG), zif-268 and
      arc, and the effects of long-term caffeine or 1,3-dipropyl-8-cyclopentylxanthine
      (DPCPX) exposure (once daily for 15 days) on striatal gene expression of
      substance P, enkephalin, and glutamic acid decarboxylase isoforms, GAD65 and
      GAD67, were evaluated in wild-type and A(2A)-R-deficient (A(2A)-R(-/-)) mice. In
      situ hybridization histochemistry was performed using oligonucleotides followed
      by quantitative image analysis. Our results demonstrated that a biphasic response
      of IEG expression to acute caffeine observed in the wild-type striatum was
      resumed in a monophasic response in the mutant striatum. In the cerebral cortex
      and hippocampus, the effect of caffeine was weak in wild-type, whereas in mutant
      mice it induced a 2-3-fold increase in the IEG expression to restore a level
      similar to the wild-type basal expression. Chronic caffeine and DPCPX-mediated
      regulation in neuropeptide and GADs striatal gene expression typically showed the
      mimicking of alterations resulting from the A(2A)-R genetic deficiency in 25
      mg/kg caffeine-treated wild-type mice as well as the dose-dependent normalization
      of substance P and enkephalin expression in A(2A)-R(-/-) mice. These results
      indicate that, depending on the dose, the blockade of A(2A)-R or A(1) receptors
      by caffeine is preferentially revealed leading to highly differential alterations
      in striatal gene expression and they also suggested the central role of these two
      receptors on the control of dopaminergic functions.

PMID- 11574943
TI  - Prenatal cocaine exposure increases mesoprefrontal dopamine neuron responsivity
      to mild stress.
AB  - Children whose mothers used cocaine during pregnancy appear to have an increased
      incidence of certain neurobehavioral deficits. Rodent models of prenatal cocaine
      exposure have mimicked these deficits in the offspring, yet the biochemical basis
      of the behavioral abnormalities is unknown. We have been able to reproduce short
      term memory deficits in our rat intravenous model of prenatal cocaine exposure,
      and as short-term memory is dependent on the function of dopamine neurons
      innervating the medial prefrontal cortex, we hypothesized that prenatal cocaine
      induces a dysfunction in the regulation of this pathway. Here we report that mild
      footshock stress, which preferentially activates the mesoprefrontal dopamine
      system, leads to an enhanced increase in dopamine turnover in the ventromedial
      prefrontal cortex of adolescent (postnatal day 35-37) rats exposed to cocaine in
      utero, suggesting that the dopamine neurons innervating this region are
      hyperresponsive in these rats. Thus, this biochemical alteration may be central
      to some of the cognitive deficits exhibited by offspring that were exposed to
      cocaine during fetal development.

PMID- 11574944
TI  - Uptake of D-serine by synaptosomal P2 fraction isolated from rat brain.
AB  - We have demonstrated that the crude synaptosome P2 fraction prepared from the rat
      brain is able to accumulate [(3)H]D-serine in a saturable, temperature-dependent
      and partially sodium- and potassium-dependent manner with an affinity of a
      hundred micromolar range. The inhibition profile of D-serine accumulation by
      various amino acids is different from those of uptake systems reported for
      glycine and other amino acids. The present data suggest that the endogenous D
      serine may be taken up mainly through a carrier-mediated transport system to
      regulate its extracellular concentration in the mammalian brain.

PMID- 11574945
TI  - Morphine acutely and persistently attenuates nonvesicular GABA release in rat
      nucleus accumbens.
AB  - Withdrawal from repeated exposure to morphine causes a long-lasting increase in
      the reactivity of nucleus accumbens nerve terminals towards excitation. The
      resulting increase in action potential-induced exocytotic release of
      neurotransmitters, associated with behavioral sensitization, is thought to
      contribute to its addictive properties. We recently showed that activation of N
      methyl-D-aspartate (NMDA) as well as dopamine (DA) D1 receptors in rat striatum
      causes tetrodotoxin-insensitive transporter-dependent GABA release. Since
      sustained changes in extracellular GABA levels may play a role in drug-induced
      neuronal hyperresponsiveness, we examined the acute and long-lasting effect of
      morphine on this nonvesicular GABA release in rat nucleus accumbens slices. The
      present study shows that morphine, through activation of mu-opioid receptors,
      reduces nonvesicular NMDA-induced [(3)H]GABA release in superfused nucleus
      accumbens slices. Moreover, prior repeated morphine treatment of rats (10 mg/kg,
      sc, 14 days) caused a reduction in NMDA-stimulated [(3)H]GABA release in vitro
      until at least 3 weeks after morphine withdrawal. This persistent neuroadaptive
      effect was not observed studying dopamine D1 receptor-mediated [(3)H]GABA release
      in nucleus accumbens slices. Moreover, this phenomenon appeared to be absent in
      slices of the caudate putamen. Interestingly, even a single exposure of rats to
      morphine (>2 mg/kg) caused a long-lasting inhibition of NMDA-induced release of
      GABA in nucleus accumbens slices. These data suggest that a reduction in
      nonvesicular GABA release within the nucleus accumbens, by enhancing the
      excitability of input and output neurons of this brain region, may contribute to
      the acute and persistently enhanced exocytotic release of neurotransmitters from
      nucleus accumbens neurons in morphine-exposed rats.

PMID- 11574946
TI  - Effects of bilateral olfactory bulbectomy on N-methyl-D-aspartate receptor
      function: autoradiographic and behavioral studies in the rat.
AB  - Rat bilateral olfactory bulbectomy (OBX) serves as a useful model in the study of
      depression and the mechanisms of action of antidepressant treatments. Considering
      the evidence of NMDA receptors involvement in depression, the present study was
      undertaken in order to investigate the time-course effects of OBX on the NMDA
      receptor function. Following bilateral olfactory bulbectomy, rats display an
      increase in locomotor activity and changes in other types of behavior in a novel
      environment. Autoradiographic experiments using the noncompetitive NMDA
      antagonist [(125)I]-iodo-MK-801 as the labeling agent showed that this increase
      in behavioral activities corresponds to a decrease in [(125)I]-iodo-MK-801
      binding in a number of brain regions. In most regions, this reduction reached
      significance by the third week following OBX. However, in some cortical areas-a
      nucleus of the thalamus (AV) and one of the amygdala (LA)-this reduction was
      already significant in the first or second week following OBX and lasted
      throughout the 4 weeks of the study. We also compared the behavioral
      modifications induced by a challenge injection of MK-801 (0.2 mg/kg i.p.) in OBX
      and sham-operated rats. This challenge is known to induce hyperlocomotion and a
      number of stereotypies in naive rats. These effects were drastically reduced in
      OBX as compared to sham-operated rats. These data are consistent with the above
      mentioned decrease in cerebral binding of MK-801 to NMDA receptors.

PMID- 11574947
TI  - Expression of serotonin 5-HT(2A) receptors in the human cerebellum and
      alterations in schizophrenia.
AB  - The occurrence of human cerebellar serotonin 5-HT(2A) receptors (5-HT(2A)R) is
      equivocal and their status in schizophrenia unknown. Using a range of techniques,
      we investigated cerebellar 5-HT(2A)R expression in 16 healthy subjects and 16
      subjects with schizophrenia. Immunocytochemistry with a monoclonal antibody
      showed labelling of Purkinje cell bodies and dendrites, as well as putative
      astrocytes. Western blots showed a major band at approximately 45 kDa. Receptor
      autoradiography and homogenate binding with [(3)H]ketanserin revealed cerebellar
      5-HT(2A)R binding sites present at levels approximately a third of that in
      prefrontal cortex. 5-HT(2A)R mRNA was detected by reverse transcriptase
      polymerase chain reaction, with higher relative levels in men than women. Several
      aspects of 5-HT(2A)R expression were altered in schizophrenia. 5-HT(2A)R
      immunoreactivity in Purkinje cells was partially redistributed from soma to
      dendrites and was increased in white matter. 5-HT(2A)R mRNA was decreased in the
      male patients. 5-HT(2A)R measured by dot blots and [(3)H]ketanserin binding
      (B(max) and K(d)) were not significantly altered in schizophrenia. These data
      show that 5-HT(2A)R gene products (mRNA, protein, binding sites) are expressed in
      the human cerebellum at nonnegligible levels; this bears upon 5-HT(2A)R imaging
      studies which use the cerebellum as a reference region. 5-HT(2A)R expression is
      altered in schizophrenia; the shift of 5-HT(2A)R from soma to dendrites is
      noteworthy since atypical antipsychotics have the opposite effect. Finally, the
      results emphasise that expression of a receptor gene is a mutifaceted process.
      Measurement of multiple parameters is necessary to give a clear picture of the
      normal situation and to show the profile of alterations in a disease.

PMID- 11574948
TI  - Comparison of paired-pulse facilitation of AMPA and NMDA synaptic currents in the
      lateral amygdala.
AB  - Stimulating thalamic fibers exiting from the internal capsule evokes a
      glutamatergic excitatory postsynaptic current (EPSC) recorded in vitro with patch
      electrodes in neurons of the rat lateral amygdala (LA). The purpose of this study
      is to compare paired-pulse facilitation (PPF), a form of short-term synaptic
      plasticity, of AMPA and NMDA receptor-mediated EPSCs. Analysis of PPF at this
      synapse is important since, in fear-conditioned animals, PPF reflects an enhanced
      transmitter release but the amplitude of only AMPA EPSCs is facilitated. PPF
      magnitude of the composite EPSC is a result of both AMPA and NMDA receptor
      activation; however, the characteristics of AMPA and NMDA PPF are dissimilar.
      Specifically, the NMDA EPSC shows greater PPF (NMDA PPF) than does the AMPA EPSC
      whether measuring the NMDA PPF magnitude in an AMPA antagonist/Mg(2+)-free
      solution or by subtracting the AMPA EPSC from the composite EPSC in normal
      Mg(2+). Presynaptic NMDA receptors neither influence AMPA PPF nor account for the
      difference between the NMDA and AMPA PPF. Another difference was that removal of
      inhibitory tone enhanced AMPA PPF, while it had mixed effects on NMDA PPF.
      Furthermore, AMPA PPF was independent of stimulus intensity and postsynaptic
      voltage, unlike the NMDA PPF. Another dissimilarity was that the amplitudes of
      pairs of AMPA EPSCs were not correlated, suggesting presynaptic mechanisms. In
      contrast, NMDA PPF was dependent on stimulus intensity and postsynaptic voltage
      and the amplitudes of paired NMDA EPSCs had a positive correlation, suggesting a
      postsynaptic influence. Both AMPA and NMDA PPF were influenced by GABA inhibition
      and this could be a factor in the magnitude disparity. These data show that AMPA
      and NMDA PPF have different characteristics and contribute to the composite PPF
      in the thalamic to lateral amygdala pathway.

PMID- 11574949
TI  - Multisite evaluation of a new dipstick for albumin, protein, and creatinine.
AB  - The goal of our study was to perform a multisite evaluation of a new urine
      dipstick called Multistix PROtrade mark (Bayer, Elkhart, IN), which has reagent
      pads for the simultaneous assay of urinary albumin, protein, and creatinine.
      Patients' urine specimens were assayed at four sites with these dipsticks and
      with the familiar Bayer Multistix 10SG dipsticks for protein. The new dipstick
      pads for albumin are impregnated with bis (3',3"-diiodo-4',4"-dihydroxy-5',5"
      dinitrophenyl)-3,4,5,6-tetrabromo-sulfonephthalein (DIDNTB) dye. These dipsticks
      also have a novel pad that estimates urinary creatinine using the peroxidase
      activity of the copper-creatinine complex. We determined the interlaboratory
      agreement of these dipsticks by comparing dipstick results to values obtained by
      quantitative analytical methods. We found that dividing the dipsticks' albumin or
      protein results by the creatinine concentration reduced the number of false
      positive albumin or protein values observed in concentrated urines, and reduced
      the number of false negatives in dilute urines. The ratio of albumin to
      creatinine, or protein to creatinine gives a better measure of albumin or protein
      excretion. Compared to reading by eye, the dipstick results agreed better with
      the quantitative assays when they were read by a reflectometer (Bayer Clinitek).

PMID- 11574950
TI  - Significance of cerebrospinal fluid adenosine deaminase isoenzymes in tuberculous
      (TB) meningitis.
AB  - Adenosine deaminase (ADA) exists as two isoenzymes, ADA(1) and ADA(2). It appears
      that the ADA(2) isoenzyme originates mainly from monocytes and macrophages. In
      tuberculous pleural effusions most of the ADA activity consists of ADA(2). The
      aim of this prospective study was to analyse ADA isoenzymes in the CSF of
      patients with meningitis to investigate whether the expected rise of the ADA(2)
      isoenzyme would occur in tuberculous meningitis. ADA isoenzyme analysis was
      performed on the CSF of 15 patients with tuberculous and 11 patients with
      bacterial meningitis by an automated kinetic enzyme coupled assay in the presence
      and absence of a specific ADA inhibitor. The ratio of ADA(2)/ADA(Total) was > 0.8
      in 14/15 patients with tuberculous meningitis. In bacterial meningitis the ratio
      was > or =0.8 in 10/11 patients. The ADA(2) isoenzyme is the major contributor to
      increased ADA activity in the CSF of patients with tuberculous meningitis,
      probably reflecting the monocyte-macrophage origin of the ADA.

PMID- 11574951
TI  - Is skeletal muscle damaged by the oxidative stress following anaerobic exercise?
AB  - We investigated whether the injury of skeletal muscle owing to the action of free
      radicals and the subsequent oxidative damage to tissues occurred during anaerobic
      exercise. To estimate injury to skeletal muscle, we determined certain indices of
      oxidative damage to skeletal muscle; i.e., leukocyte counts, concentrations of
      hypoxanthine, xanthine, urate, tissue- and serum-type CK-M isoforms, myoglobin,
      and total antioxidant capacity (TAC) of serum. Blood for these tests was
      collected at 3 min post-exercise. Post-anaerobic exercise concentrations of
      lactate were significantly increased from pre-exercise. The neutrophil and
      lymphocyte counts and alanine concentration were significantly increased by
      anaerobic exercise, even when the results were corrected for plasma volume
      changes; the plasma concentrations of hypoxanthine, urate, and TAC of serum were
      also significantly increased. The plasma concentration of xanthine was negatively
      correlated with TAC of serum. The activities of tissue- and serum-type CK-M were
      significantly increased post-exercise. When the hypoxanthine, urate, TAC of
      serum, myoglobin, and tissue- and serum-type CK-M were corrected for plasma
      volume changes, the post-exercise increases were no longer significantly
      different from the pre-exercise results. We suggest that these latter test
      results following anaerobic exercise exclude the presence of oxidative damage to
      skeletal muscle.

PMID- 11574952
TI  - Rapid in vitro conversion of fosphenytoin into phenytoin in sera of patients with
      liver disease: role of alkaline phosphatase.
AB  - Fosphenytoin, a phosphate ester pro drug of phenytoin, also cross-reacts with the
      fluorescence polarization immunoassay (FPIA) for phenytoin. We measured
      fosphenytoin concentrations using the FPIA kit and TDx analyzer. We prepared
      serum pools from normal volunteers and patients with liver disease. None of them
      received either fosphenytoin or phenytoin. Fosphenytoin standard solution (1
      mg/ml) was prepared in water. We supplemented aliquots of normal and liver pools
      with known amounts of fosphenytoin and measured the concentrations at different
      time intervals. The conversion of fosphenytoin to phenytoin was slow in sera with
      normal alkaline phosphatase activities. The conversion was rapid in sera
      collected from patients with liver disease who also had high alkaline phosphatase
      activities. The observed concentrations were close to target concentrations
      within 0-2 min of supplementation with fosphenytoin. Surprisingly, the observed
      concentration then started to decline slightly but significantly with longer
      incubation time. In contrast, the observed concentration increased steadily in
      serum with normal alkaline phosphatase activity. For example, in the normal pool
      supplemented with 15.0 microg/ml fosphenytoin (as the phenytoin equivalent), the
      observed concentrations were 6.9, 7.3, 7.7, 8.3, and 9.8 microg/ml at 0-2, 10,
      20, 30, and 60 min, respectively. However, in a serum pool prepared from patients
      with liver disease and supplemented with 15.0 microg/ml of fosphenytoin (alkaline
      phosphatase: 2547 U/l), the observed phenytoin concentrations were 12.9, 12.1,
      11.0, 10.7, and 10.7 microg/ml at 0-2, 10, 20, 30, and 60 min, respectively. When
      we added alkaline phosphatase to the normal serum pool, we observed rapid
      conversion of fosphenytoin into phenytoin within 10 min, but the concentrations
      then declined with longer incubation time. However, when we repeated the
      experiment with protein-free ultrafiltrate, we observed rapid conversion of
      fosphenytoin to phenytoin, but the concentration did not decline with longer
      incubation time.

PMID- 11574953
TI  - Relation of polymorphism in the promotor region for the human osteocalcin gene to
      bone mineral density and occurrence of osteoporosis in postmenopausal Chinese
      women in Taiwan.
AB  - Osteoporosis is a common disorder with a strong genetic component. Our aim was to
      evaluate the correlation of the HindIII osteocalcin gene polymorphism to bone
      mineral density (BMD) and their relationship to osteoporosis. We determined the
      HindIII osteocalcin gene polymorphism using polymerase chain reaction (PCR)-based
      restriction analysis in postmenopausal Chinese women in Taiwan. The osteocalcin
      gene polymorphism was detected by the restriction enzyme HindIII, where the H
      allele indicated the absence of the cuttable site and the h allele indicated its
      presence. We then related the genotypes to BMD and occurrence of osteoporosis in
      these women. The allelic frequencies for postmenopausal Chinese women in Taiwan
      were 64% for h and 36% for H in HindIII restriction fragment length
      polymorphisms. The prevalence of each genotype in the study population was 37.7%
      hh, 52.6% Hh, and 9.7% HH. The subjects with genotype hh had the greatest BMD at
      the lumbar spine and the femoral neck, and those with HH had the smallest BMD at
      the femoral neck, but these differences did not reach statistical significance.
      The HindIII osteocalcin genotype showed a significant effect on the prevalence of
      osteoporosis in the subjects at the femoral neck, that is, women with genotype HH
      had a 6.4 times greater risk for osteoporosis (P < 0.05), and those with genotype
      Hh had a 1.2 times greater risk than women with genotype hh. In conclusion, the
      HindIII osteocalcin gene polymorphism is associated with reduced BMD and
      predisposes women to osteoporosis at the femoral neck.

PMID- 11574954
TI  - Detection of apoB-100 R3500Q mutation by competitive allele-specific polymerase
      chain reaction.
AB  - The apolipoprotein B-100 mutation R3500Q is one of the most common inherited
      defects causing abnormality of the lipid metabolism. We describe a one-step,
      single-tube PCR technique for detection of the mutation based on competition
      between allele-specific primers. Three oligonucleotides are used: two allele
      specific primers differing in their 3' nucleotide (for the wild-type and the
      mutant allele) together with a common primer, resulting in simultaneous
      amplification of both alleles. This provided internal control of successful
      amplification and is expected to result in increased specificity. The allele
      specific primers differ also in length, allowing us to distinguish both alleles
      by their size in a single electrophoretic run. For optimization of the protocol,
      DNAs genotyped before by oligonucleotide ligation assay were used. The individual
      genotypes obtained by CAS-PCR coincided fully with the ones from a referent OLA
      test: seven heterozygous individuals were found, 4 of them among 150 unrelated
      hypercholesterolemic individuals studied and other three in the pedigrees of
      heterozygous carriers. On the overall 160 genotypes were determined, neither
      false-positive (0 out of 153 non-carriers) nor false-negative (0 out of 7
      carriers) results were obtained. No homozygous mutant genotypes were identified
      in this sample.

PMID- 11574955
TI  - Ratio of baseline erythropoietin (EPO) level and corrected reticulocyte count as
      an indicator for a favourable response to recombinant human erythropoietin
      (rhEPO) therapy in anaemic cancer patients.
AB  - PURPOSE: Recently, recombinant human erythropoietin (rhEPO) was introduced for
      the management of anemia in malignancy. To identify an indicator for a favourable
      response to rhEPO, 28 anaemic cancer patients undergoing chemotherapy and treated
      with rhEPO were evaluated. METHODS: Patients were classified into responder (16
      of 28, 57%) and nonresponder (12 of 28, 43%) groups according to their responses
      to rhEPO therapy (response being defined as an increase in Hb level of > 2 g/dl
      from baseline without blood transfusion). RESULTS: Treatment with rhEPO showed
      significant improvements in the red blood cell (RBC) count, haemoglobin (Hb),
      packed cell volume (PCV), and reticulocyte count (ret. count) after 4 weeks. Upon
      analysing the baseline value of the EPO level and the corrected ret.count in
      these two groups, we found that the ratio of the EPO level and the corrected
      ret.count (EPO/ret.count) demonstrated a statistical significance (P = 0.03) in
      the prediction of response to rhEPO therapy. This ratio showed a sensitivity of
      87.5%, specificity of 66.7%, and overall accuracy of 78.6%. CONCLUSION: Our study
      suggested that the baseline ratio of EPO/ret.count should be used as an indicator
      for a favourable response to rhEPO therapy.

PMID- 11574956
TI  - Reticulocytes and reticulocyte enumeration.

PMID- 11574957
TI  - Albuminuria and proteinuria in hospitalized patients as measured by quantitative
      and dipstick methods.
AB  - We tested patients' urines for albumin, protein, and creatinine by quantitative
      and dipstick methods. The concentrations of these analytes were established by
      quantitative, cuvet-based chemistry methods that we assumed gave the "correct"
      values. There was good to excellent agreement of the dipstick results with the
      quantitative methods for the above three analytes. We found many patients who
      excreted pathological amounts of albumin and/or protein who did not have a
      diagnosis of kidney disease or other likely causes of proteinuria, suggesting
      that albuminuria and/or proteinuria were underdiagnosed in our group of patients.
      Those with cardiovascular disease, kidney disease, or diabetes showed the
      greatest predictive value of a positive test for albumin or protein by dipstick.
      Dipstick testing for albumin, protein, and creatinine had good or excellent
      agreement with quantitative methods. The dipstick tests were easy to use, simple,
      and low in cost, and can serve well for point-of-care testing.

PMID- 11574958
TI  - Adaptive control of mobile robots using a neural network.
AB  - A Neural Network - based control approach for mobile robot is proposed. The
      weight adaptation is made on-line, without previous learning. Several possible
      situations in robot navigation are considered, including uncertainties in the
      model and presence of disturbance. Weight adaptation laws are presented as well
      as simulation results.

PMID- 11574959
TI  - Backpropagation algorithm adaptation parameters using learning automata.
AB  - Despite of the many successful applications of backpropagation for training multi
      layer neural networks, it has many drawbocks. For complex problems it may require
      a long time to train the networks, and it may not train at all. Long training
      time can be the result of the non-optimal parameters. It is not easy to choose
      appropriate value of the parameters for a particular problem. In this paper, by
      interconnection of fixed structure learning automata (FSLA) to the feedforward
      neural networks, we apply learning automata (LA) scheme for adjusting these
      parameters based on the observation of random response of neural networks. The
      main motivation in using learning automata as an adaptation algorithm is to use
      its capability of global optimization when dealing with multi-modal surface. The
      feasibility of proposed method is shown through simulations on three learning
      problems: exclusive-or, encoding problem, and digit recognition. The simulation
      results show that the adaptation of these parameters using this method not only
      increases the convergence rate of learning but it increases the likelihood of
      escaping from the local minima.

PMID- 11574960
TI  - Design of a neurofuzzy controller with simplified architecture.
AB  - This work presents the design of a neurofuzzy controller with simplified
      architecture that minimizes the processing time used in several stages associated
      with systems and processes modelling. The basic procedures of fuzzification and
      defuzzification are very simplified, whereas the inference procedures are
      computed in a direct way. The simplified architecture has allowed a fast and easy
      configuration of the neurofuzzy controller, as consequence, the control rules
      that define the control actions are obtained automatically. To validate the
      proposed approach, this neurofuzzy system is used in an industrial application
      for fluid flow control.

PMID- 11574961
TI  - CDMA and TDMA based neural nets.
AB  - CDMA and TDMA telecommunication techniques were established long time ago, but
      they have acquired a renewed presence due to the rapidly increasing mobile phones
      demand. In this paper, we are going to see they are suitable for neural nets, if
      we leave the concept "connection" between processing units and we adopt the
      concept "messages" exchanged between them. This may open the door to neural nets
      with a higher number of processing units and flexible configuration.

PMID- 11574963
TI  - Training SVMs with EDR algorithm.
AB  - The aim of this work is to present a new training algorithm for SVMs based on the
      pattern selection strategy called Error Dependent Repetition (EDR). With EDR, the
      presentation frequency of a pattern depends on its error: patterns with larger
      errors are selected more frequently and patterns with smaller error (or learned)
      are presented with minor frequency. Using a simple iterative process based on
      gradient ascent, SVM-EDR can solve the dual problem without any assumption about
      support vectors or the Karush-Kuhn-Tucker (KKT) conditions.

PMID- 11574962
TI  - A study on rule extraction from several combined neural networks.
AB  - The problem of rule extraction from neural networks is NP-hard. This work
      presents a new technique to extract "if-then-else" rules from ensembles of DIMLP
      neural networks. Rules are extracted in polynomial time with respect to the
      dimensionality of the problem, the number of examples, and the size of the
      resulting network. Further, the degree of matching between extracted rules and
      neural network responses is 100%. Ensembles of DIMLP networks were trained on
      four data sets in the public domain. Extracted rules were on average
      significantly more accurate than those extracted from C4.5 decision trees.

PMID- 11574964
TI  - Recent advances in the MOBJ algorithm for training artificial neural networks.
AB  - This paper presents a new scheme for training MLPs which employs a relaxation
      method for multi-objective optimization. The algorithm works by obtaining a
      reduced set of solutions, from which the one with the best generalization is
      selected. This approach allows balancing between the training error and norm of
      network weight vectors, which are the two objective functions of the multi
      objective optimization problem. The method is applied to classification and
      regression problems and compared with Weight Decay (WD), Support Vector Machines
      (SVMs) and standard Backpropagation (BP). It is shown that the systematic
      procedure for training proposed results on good generalization neural models, and
      outperforms traditional methods.

PMID- 11574965
TI  - A proposed max-product threshold unit for classification of pattern vectors.
AB  - This paper proposes a max-product threshold unit (maptu) that can successfully
      perform dichotomous classifications of pattern vectors. Maptu, with weight
      vector, w, classifies a pattern vector, x, by comparing x max-prod w to 0.5.
      Results obtained by other methods in classification of benchmark data are used
      for comparison to the method using maptu. The benchmark data consists of the
      Australian credit data set, cervical cell data set, diabetes data set and the
      iris data set.

PMID- 11574966
TI  - Three case studies of the GasNet model in discrete domains.
AB  - A new neural network model - the GasNet - has been recently reported in the
      literature, which, in addition to the traditional electric type, point-to-point
      communication between units, also uses communication through a diffilsable
      chemical modulator. Here we assess the applicability of this model in three
      different scenarios, the XOR problem, a food gathering task for a simulated
      robot, and a docking task for a virtual spaceship. All of them represent discrete
      domains, a contrast with the one where the GasNet was originally introduced,
      which had an essentially continuous nature. These scenarios are well-known
      benchmark problems from the literature and, since they exhibit varying degrees of
      complexity, they impose distinct performance demands on the GasNet. The
      experiments were primarily intended to better understand the model, by extending
      the original problem domain where GasNet was introduced. The results reported
      point at some difficulties with the current GasNet model.

PMID- 11574967
TI  - A late-stopping method for optimal aggregation of neural networks.
AB  - Ensembles of artificial neural networks have been used in the last years as
      classification/regression machines, showing improved generalization capabilities
      that outperform those of single networks. However, it has been recognized that
      for aggregation to be effective the individual networks must be as accurate and
      diverse as possible. An important problem is, then, how to tune the aggregate
      members in order to have an optimal compromise between these two conflicting
      conditions. We propose here a simple method for constructing
      regression/classification ensembles of neural networks that leads to overtrained
      aggregate members with an adequate balance between accuracy and diversity. The
      algorithm is favorably tested against other methods recently proposed in the
      literature, producing an improvement in performance on the standard statistical
      databases used as benchmarks. In addition, and as a concrete application, we
      apply our method to the sunspot time series and predict the remainder of the
      current cycle 23 of solar activity.

PMID- 11574968
TI  - A goal-driven neural propositional interpreter.
AB  - This work presents ARQ-PROP-II, the propositional version of a neural engine for
      finding proofs by refutation using the Resolution Principle. This neural
      architecture does not require special arrangements or modules to do forward or
      backward reasoning, being driven by the goal posed to it. ARQ-PROP-II is capable
      of integrated monotonic reasoning with complete and incomplete knowledge. The
      neural mechanism presented herein is the first to our knowledge that does not
      require that the knowledge base be either pre-encoded or learnt.

PMID- 11574969
TI  - Family practice between the waves.

PMID- 11574970
TI  - Defining medical necessity.

PMID- 11574971
TI  - Lists welcome here.

PMID- 11574973
TI  - Coding and documentation. Answers to your questions.

PMID- 11574972
TI  - Medicare clarifies preoperative services reimbursement policy.

PMID- 11574974
TI  - Seven reasons to dictate in the presence of your patients.

PMID- 11574975
TI  - Is it time to re-examine family practice?

PMID- 11574976
TI  - Involving patients in medical decisions: what happens in real-world practice?

PMID- 11574977
TI  - Effect of dehydroepiandrosterone and its sulfate metabolite on neuronal cell
      viability in culture.
AB  - BACKGROUND: The neurosteroids dehydroepiandrosterone (DHEA) and its sulfated
      metabolite (DHEAS) have been reported to possess neuroprotective as well as anti
      tumoral activity in vitro and in vivo. OBJECTIVES: To compare the effect of the
      two neurohormones on cell viability in primary whole-brain fetal mouse culture
      and isolated neuronal culture, as well as in a human neuroblastoma cell line (SK
      N-SH). METHODS: Cell viability and cell proliferation were determined with the
      neutral red and 3H-thymidine uptake methods. Apoptosis in propidium iodide
      stained neuroblastoma cells was determined using flow cytometry. RESULTS: DHEA (1
      nM-10 microM) decreased the viability of selected primary neuronal cells (33-95%
      after 24 and 72 hours) but not of whole-brain cultured cells (neuron + glia).
      DHEAS did not significantly modify cell viability in either primary culture. In a
      human neuroblastoma cell line, DHEA (1 nM-1 microM) decreased 3H-thymidine uptake
      (30-60%) and cell viability (23-52%) after 24 hours. DHEAS did not significantly
      modify, or only slightly stimulated, cell viability and uptake of 3H-thymidine
      (132% of controls). The combination of DHEA and DHEAS neutralized the toxic
      effect of DHEA in both primary neuronal culture and neuroblastoma cell line. Flow
      cytometric analysis of DNA fragmentation in neuroblastoma cells treated with 100
      nM DHEA/DHEAS for 24 hours showed an increase in apoptotic events (31.9% and
      26.3%, respectively, vs. control 2.54%). CONCLUSIONS: Our results do not confirm
      a neuroprotective role for DHEA and suggest that DHEA and DHEAS have a
      differential role; DHEA possesses a neurotoxic (expressed only in isolated
      neurons) and anti-proliferative effect; DHEAS demonstrates only a slight
      neuroprotective effect.

PMID- 11574978
TI  - Amelioration of experimental colitis by thalidomide.
AB  - BACKGROUND: Rectal administration of iodoacetamide induces colitis by blocking
      sulphhydryl groups and generating inflammatory mediators. Thalidomide, a non
      barbiturate hypnotic, also has an anti-inflammatory effect, presumably by
      suppressing the production of tumor necrosis factor alpha. In patients with
      Crohn's disease, neutralization or suppression of TNF alpha reduces inflammation.
      OBJECTIVES: To evaluate the effects of thalidomide in a model of experimental
      colitis. METHODS: Colitis was induced in rats by intracolonic administration of
      3% iodoacetamide. In the treatment group, thalidomide 50 mg/kg was given daily by
      gavage and continued for 7 days until the rats were sacrificed. Their colons were
      then processed for wet weight, lesion area, weight of mucosal scraping,
      myeloperoxidase activity and histology. Serum levels of TNF were determined.
      RESULTS: Colonic wet weight, lesion area, myeloperoxidase activity and serum
      levels of TNF alpha were significantly lower (P < 0.05) in the treatment group
      (iodoacetamide + thalidomide) than the control group (iodoacetamide only).
      Histologically, colonic inflammation in the treated group was markedly decreased.
      CONCLUSIONS: Thalidomide effectively decreases colitis induced by iodoacetamide.
      The mechanism is probably associated with inhibition of TNF alpha, and should be
      further studied.

PMID- 11574979
TI  - Ultrasound-guided thrombin injection for the treatment of iatrogenic
      pseudoaneurysm of the femoral artery.
AB  - BACKGROUND: Pseudoaneurysm occurring after catheterization of the femoral artery
      is associated with significant morbidity. Percutaneous ultrasound-guided thrombin
      injection has recently emerged as a potential first-line therapy. OBJECTIVES: To
      evaluate the efficacy of this treatment in eight patients with iatrogenic femoral
      artery pseudoaneurysm. METHODS: After attempted treatment with external
      compression had failed, eight patients with iatrogenic femoral artery
      pseudoaneurysm were treated with thrombin injection. Treatment performed between
      2 and 9 days following arterial puncture. The study group comprised seven males
      and one female ranging in age from 23 to 89 years (median 70). Seven had
      undergone cardiac catheterization with or without intervention, and five were
      receiving antiplatelet and/or anticoagulant drugs. Arterial pseudoaneurysm
      resulted from femoral vein catheterization in one patient. Using a sterile
      technique and real-time Doppler ultrasound guidance, a dilute solution of bovine
      thrombin (average dose 250 units, range 100-600), was slowly injected directly
      into the pseudoaneurysm until cessation of flow was seen. Patients were allowed
      to walk within 2 hours of the procedure and were followed up clinically and by
      color Doppler ultrasound during the admission. RESULTS: Cardiac catheterization
      had been inadvertently performed via the superficial or profunda femoris arteries
      in four of the eight patients. Thrombin injection was initially successful in all
      eight patients without complication. Thrombosis occurred immediately in every
      case. Early recanalization of pseudoaneurysm occurred in one patient despite
      repeat thrombin injection and attempted ultrasound-guided compression. He
      eventually required surgical repair. The final success rate was 87.5% (7/8).
      CONCLUSION: Faulty puncture technique is an important risk factor for the
      development of post-catheterization femoral artery pseudoaneurysm. Ultrasound
      guided thrombin injection is a safe, rapid, well-tolerated, inexpensive and
      successful therapy. If initial external compression with a sandbag fails to
      result in thrombosis of the pseudoaneurysm then thrombin injection should be
      considered as first-line therapy. If unsuccessful, it does not preclude the use
      of alternative treatment modalities. Further study is necessary to assess the
      long-term effects of thrombin injection.

PMID- 11574980
TI  - Etiology and incidence of endotracheal intubation following spinal anesthesia for
      cesarean section.
AB  - BACKGROUND: The incidence of spinal failure necessitating general anesthesia and
      endotracheal intubation following spinal anesthesia for cesarean section is
      extremely low. Aspiration prophylaxis prior to spinal anesthesia is often
      recommended in case of spinal failure or excessive spinal block requiring the
      emergency administration of general anesthesia. OBJECTIVES: To determine the
      incidence of endotracheal intubation following spinal anesthesia for cesarean
      section. METHODS: We retrospectively reviewed the peri-operative course of
      parturients undergoing cesarean section under spinal anesthesia at our
      institution from February 1991 to December 1993. If spinal failure occurred, 10
      ml of sodium bicarbonate was administered by mouth prior to induction of general
      anesthesia. RESULTS: Among the 743 cases that we reviewed, spinal failure
      occurred in 15 patients (2%) because of inadequate analgesia in 14 patients
      (1.9%) and unexpected prolonged surgery for hysterectomy in one patient (0.1%).
      No patient required intubation due to excessive spinal block. In none of the
      patients was a record of pulmonary aspiration identified. CONCLUSIONS: The
      extremely low incidence of spinal failure or excessive block necessitating
      endotracheal intubation suggests that routine aspiration prophylaxis may not be
      necessary prior to spinal anesthesia. However, these results should be confirmed
      by a prospective, controlled study on larger populations. An antacid should be
      readily available and administered whenever general anesthesia is required.

PMID- 11574981
TI  - The dietary composition of pre-fast meals and its effect on 24 hour food and
      water fasting.
AB  - BACKGROUND: Fasting is required by the Jewish and Islamic religions, and may
      sometimes be necessary for non-religious reasons as well. Very little empiric
      data are available on the effect of 24 hours of food and water deprivation.
      OBJECTIVES: To compare the effects of the dietary composition of different pre
      fast meals on subjective discomfort and various other parameters of a 24 hour
      food and water fast. METHODS: Thirteen volunteers of both genders participated in
      a non-randomized crossover study. Each consumed three different equicaloric pre
      fast meals in which the main source of calories was protein (49% of calories),
      carbohydrate (86%), or fat (69%). Weight, heart rate, blood pressure, blood and
      urine were tested before and after 24 hours of fasting, and the subjective
      evaluations of the discomfort during the three fasts were compared. RESULTS:
      After the protein-rich meal greater discomfort and more side effects were
      reported. Weight and blood pressure decreased at the end of the fasts that
      followed each of the three meals; heart rate increased after the high fat and
      carbohydrate meals but not after the protein meal. The main laboratory findings
      were a 40% increase in blood urea nitrogen and higher urine osmolarity after the
      protein-rich meal than after the other meals. CONCLUSION: A protein-poor pre-fast
      meal is likely to be followed by easier fasting.

PMID- 11574982
TI  - Urinary incontinence in women: prevalence, characteristics and effect on quality
      of life. A primary care clinic study.
AB  - BACKGROUND: Urinary incontinence in older women is common. Its characteristics
      and impact on quality of life is not well established since these women are
      usually reluctant to tell their healthcare providers about the problem.
      OBJECTIVE: To determine the characteristics of urinary incontinence in women and
      the manner in which it affects patients' quality of life. METHODS: Twenty family
      physicians were requested to distribute a questionnaire to the first 25
      consecutive women aged 30 to 75 years who visited their clinic for any reason.
      The questionnaire covered general health issues, symptoms of urinary
      incontinence, and quality of life. RESULTS: A total of 418 women, mean age 50.0
      +/- 11.8 years, completed the questionnaire (84% response rate). Of these, 148
      (36%) reported having episodes of urinary incontinence. Urinary incontinence was
      found to be associated with older age, menopause, obesity and coexisting chronic
      disorders. Sixty percent of the women with urinary incontinence found it to be a
      disturbing symptom, and 44% reported that it had a detrimental effect on their
      quality of life. Only 32% of the affected women had sought medical advice, half
      of them from their family physician. Treatment was recommended to 66% of those
      who sought help, and in about two-thirds of these it brought some measure of
      relief. CONCLUSIONS: Urinary incontinence is a common complaint among women
      attending primary care clinics, but it does not receive appropriate attention.
      Though it often adversely affects quality of life, only a small proportion of
      women seek medical advice. Family physicians should raise the issue as a part of
      the routine general health check-up.

PMID- 11574983
TI  - Fasting, food composition, health and belief.

PMID- 11574984
TI  - Rheumatoid arthritis: the future is not yet now.

PMID- 11574985
TI  - How B12 deficiency can impact on the individual and how society can impact on B12
      deficiency.

PMID- 11574987
TI  - Reactive arthritis.
AB  - Reactive arthritis is a disease affecting mostly young adults. Owing to a greater
      general awareness the diagnosis has become more common during recent years. It is
      well established that ReA is caused by an infection, mostly in genetically
      susceptible individuals. The pathogenetic mechanisms are still poorly understood,
      and the treatment rests mainly on anti-inflammatory drugs or steroids. Vigorous
      and early treatment of the triggering infection may prevent the development of
      ReA but this is rarely possible in everyday clinical practice. Despite its name,
      the disease should be considered as a general disorder that affects not only the
      joints. The prognosis is not as good as earlier believed, and relapses or chronic
      development are not unusual.

PMID- 11574986
TI  - Rheumatoid arthritis as an autoimmune disease caused by Proteus urinary tract
      infections: a proposal for a therapeutic protocol.

PMID- 11574988
TI  - Tumor necrosis factor inhibitors: new options for treating rheumatoid arthritis.
AB  - There is accumulating evidence that tumor necrosis factor plays a major role in
      the pathogenesis of rheumatoid arthritis. Recent biotechnological advances have
      allowed for the development of agents that directly target TNF, a proinflammatory
      cytokine. In the last 2 years, the U.S. Food and Drug Administration and the
      European Union's Commission of the European Communities have approved two
      biological agents for the treatment of refractory RA, etanercept and infliximab.
      Etanercept is a fusion protein, composed of the Fc portion of immunoglobulin G1
      and the extracellular domain of a TNF receptor (p75). Infliximab is a chimeric
      monoclonal antibody composed of murine variable and human constant regions. In
      placebo-controlled trials, both agents have proven to be effective and well
      tolerated in RA patients.

PMID- 11574989
TI  - The status of hemoglobin-based red cell substitutes.
AB  - Red cell substitutes are currently under development for use in a variety of
      surgery and trauma-related clinical conditions. The need for artificial oxygen
      carrying fluids continues to be driven by the shortage of donor blood, the
      complex logistics of blood banking, the risk of virally transmitted diseases,
      current transfusion practices, and the projected increased demand for blood
      products in the future. The effort to develop a replacement for the red cell
      component has evolved over the last century and has presented a number of
      significant challenges including safety and efficacy concerns. Recent progress in
      understanding the fundamental interactions of hemoglobin with the body at the
      molecular, cellular and tissue levels has led to the production of improved red
      cell substitutes suitable for clinical testing. Currently, seven products are
      being tested for a variety of applications including trauma, surgery, sepsis,
      cancer and anemia. Although some of these trials were unsuccessful, the majority
      of the available products exert no toxicity or only low level side effects.
      Encouraging results in early clinical trials with oxygen-carrying fluids support
      further development of these products and have increased the hope that a usable
      oxygen-carrying fluid will soon be available in the clinic. The purpose of this
      review is to provide up-to-date information on the status of these products with
      special emphasis on pre-clinical and clinical experience.

PMID- 11574990
TI  - Shrinkage of melanoma metastases following high dose intravenous immunoglobulin
      treatment.

PMID- 11574991
TI  - Suprapatellar pouch rupture in acute gouty arthritis.

PMID- 11574992
TI  - Cobalamin-responsive psychosis as the sole manifestation of vitamin B12
      deficiency.

PMID- 11574993
TI  - Myalgia, fever, abnormal muscle enzymes and blue urine in a farmworker from
      Thailand.

PMID- 11574994
TI  - Gingival hypertrophy due to drugs.

PMID- 11574995
TI  - First national workshop on treatment modalities for healing chronic wounds.

PMID- 11574996
TI  - Levonorgestrel-releasing IUD and breast cancer.

PMID- 11574997
TI  - Beryllium-induced lung disease.

PMID- 11574998
TI  - Venous hyperoxemia may be multifactorial.

PMID- 11574999
TI  - Ten years of recurrent syncope due to mastocytosis.

PMID- 11575000
TI  - [Respiratory problems in children after severe pneumonia].
AB  - In the course of complicated pneumonia in children diffuse inflammatory
      infiltrations with the risk of durable destruction of lung parenchyma are
      confirmed clinically and radiologically. The aim of the study was an evaluation
      of the general health state and respiratory problems in 55 children who had been
      earlier hospitalized for pneumonia with signs of localized changes and severe
      symptoms. The evaluation was done 2-10 years after the onset of the disease. In
      89.1% of children a planned treatment was continued after hospital discharge. The
      period of recovery lasted over 6 weeks in 50.8% of examined children, and it was
      shorter than 2 weeks only in 23.6% of children. The relapses of the lower
      respiratory tract inflammation occurred in 43.6% of children in the form of
      bronchitis and in 9.1% of children a recurrent pneumonia was diagnosed. Only
      12.7% of children needed subsequent hospitalization for respiratory problems. In
      34.5% of children a limitation of physical activity was noted. 40 children
      underwent a functional examination of the respiratory system. In this group 35%
      of children ventilation problems of restrictive character were stated, whereas in
      17.5% spirometry revealed bronchial obstruction. Presented results suggest the
      necessity of the specialistIc care of children after severe pneumonia including
      the monitoring of clinical and spirometric parameters of respiratory function and
      adequate rehabilitation.

PMID- 11575001
TI  - [Levels of soluble thrombomodulin in blood of patients with lung cancer].
AB  - Thrombomodulin /TM/ is a surface glycoprotein involved in the regulation of blood
      coagulation and fibrinolysis. TM has been reported to be expressed in variety of
      tumors. The purpose of this study was to evaluate the concentration of soluble TM
      in patients with planoepithelial lung cancer. Study group consisted of 33
      patients aged 51 years in IB /15/ and IIIB /18/ stage of cancer and 20 adults as
      control. Concentration of TM in plasma with ELISA method was performed. Mean
      level of TM in lung cancer patients was 4.98 +/- 0.94 ng/ml and was similar to
      control--4.60 +/- 0.88 ng/ml. No significant differences were found between
      patients with IB and IIIB stage of cancer.

PMID- 11575002
TI  - [Sarcoid reaction in patients with lung neoplasm--personal experiments].
AB  - In two cases histological examination of the lymph nodes excised during
      mediastinoscopy showed non-caseous epithelioid granulomas. In one patient with
      hilar lymphadenopathy sarcoidosis was misdiagnosed. One-year later progression of
      lesions in lungs was found and adenocarcinoma was diagnosed. In second patient
      with tumour in chest x-ray examination after misdiagnosed sarcoidosis thoracotomy
      was done and histological examination of samples from tumour showed nonsmall cell
      lung cancer. In both carcinomatous cases sarcoid reaction was recognised.

PMID- 11575003
TI  - [Differential cell count of sputum in patients with asthma challenged with
      allergen provocation].
AB  - Inhalation of hypertonic saline aerosol is a noninvasive method of obtaining
      sputum for examination of inflammatory processes in the airways. The aim of our
      investigation was to evaluate the effect of the bronchial provocation test with
      Dermatophagoides pteronyssinus on both total and differential cell counts in the
      sputum of allergic asthma patients. The studies were carried out on 20 mild or
      moderate allergic asthmatics. In each case the studies were performed on three
      consecutive days. Sputum was induced on the first day of the study, the next day
      the bronchial provocation test with the allergen was performed and on the last
      day the sputum induction was repeated again. Twenty-four hours after the allergen
      challenge an increase in the total cell count and in eosinophils and a decrease
      in the percentage of macrophages were found in the induced sputum. The above
      changes were more marked in the patients demonstrating the dual asthmatic
      reaction after allergen challenge.

PMID- 11575004
TI  - [Pulmonary tuberculosis during a course of ankylosing spondylitis].
AB  - 61 years old man with 30-years history of ankylosing spondylitis was admitted to
      hospital because of respiratory and cardiac failure. Chest X-ray and CT scan
      showed nonspecific inflammation but microbiological diagnosis allowed to
      establish the diagnosis of pulmonary tuberculosis. During antibioticotherapy and
      antituberculous treatment respiratory failure regressed.

PMID- 11575005
TI  - [Allergic broncho-pulmonary tuberculosis--a case without bronchial asthma].
AB  - Aspergillus fumigatus can cause a number of lung diseases. One of them is
      allergic bronchopulmonary aspergillosis (ABPA) characterized by pulmonary
      eozynophilia, asthma, an allergic type of immune response in the bronchi and
      proximal bronchiectases. ABPA was recognised in 28-years old man (round shadows
      in the lung, obturated bronchus with mucoid impaction, positive skin tests with
      aspergillin and presence of precipitins to Aspergillus fumigatus, elevated serum
      IgE level). Patient was treated for 6 months with corticosteroids. After 2 years
      of regression there was an exacerbation of ABPA was recognised. The steroid
      therapy was repeated.

PMID- 11575006
TI  - [Alveolar hemorrhage caused by exposure to pesticides].
AB  - 17 years old boy was admitted because of cough, hemoptysis and mild fever. These
      symptoms appeared a day after exposure to Decis-pesticide of relatively low
      toxicity for people. In hospital respiratory failure (pO2 48.5 mmHg) and alveolar
      haemorrhage (the presence of bloody fluid with hemosiderin loaded macrophages,
      the signs of alveolar filling in chest HRCT scan and elevation of diffuse
      capacity) were recognised. All symptoms completely disappeared after 5 month of
      corticosteroids therapy.

PMID- 11575007
TI  - [Psychological and psychiatric consequences of obstructive sleep apnea].

PMID- 11575008
TI  - [The effect of second generation histamine antagonists on the heart].
AB  - The review summarizes recent progress in the study of the cardiac actions of
      second--generation antihistamines. Terfenadine and astemizole, two antihistamines
      of the second generation, are in vitro potent blockers of potassium channels
      (K+). It has been considered to be responsible for QT prolongation of the
      electrocardiogram and life--treating ventricular tachycardias called torsades de
      pointes. Loratadine and descarboethoxyloratadine, the major metabolite of
      loratadine were studied on a human cardiac K+ channel (hKv 1.5) cloned from human
      ventricle. Parent compound and its metabolite in high concentration blocked
      hKv1.5 channels. However, loratadine (10 mumol/L) failed to inhibit HERG
      potassium channel and HERG K+. Ebastine also inhibit potassium channels, cloned
      human Kv 1.5. Cetirizine was completely devoid of any inhibitory action on HERG
      K+ channels in concentration up to 30 mumd/L. On the other hand terfenadine and
      astemizole effectively blocked HERG K+ channels with nanomolar affinities (330
      and 480 nmol/L, respectively), whereas loratadine was about 300-fold less potent.
      Fexofenadine--the major metabolite of terfenadine, does not block either HERG or
      Kv1.5. The quinea pig model (in vitro) revealed that only terfenadine, astemizole
      and ebastine produced significant QT interval prolongation and arrhythmogenic
      effects. The other nonsedating antihistamines including cetirizine, loratadine
      and the major metabolite of ebastine (carabastine), terfenadine (feksofenadine)
      and astemizole (norastemizole) were devoid of QT interval prolongation and other
      adverse ECG effects.

PMID- 11575009
TI  - 'Freshly washed little cherubs'.

PMID- 11575010
TI  - Improving dental access.

PMID- 11575011
TI  - Soft drinks and caries.

PMID- 11575012
TI  - Unsupported conclusions?

PMID- 11575013
TI  - Removal loops.

PMID- 11575014
TI  - JADA online has arrived.

PMID- 11575015
TI  - Porphyromonas gingivalis genome sequenced.

PMID- 11575016
TI  - Using packable composites for direct posterior placement.
AB  - BACKGROUND: Although dentists have been using resin-based composites successfully
      to restore posterior teeth in Class II situations for several years, creating a
      functional, anatomical proximal contact remains a clinical challenge for many
      clinicians. OVERVIEW: This article presents a step by-step technique for creating
      a predictable proximal contact using a packable resin-based composite as the
      restorative material. Using a technique that is similar to that for amalgam will
      enable the dentist to make a successful transition to using composite as an
      alternative to amalgam in some posterior teeth. PRACTICE IMPLICATIONS: More
      patients today are well-informed about dental care and are seeking tooth-colored
      restorative alternatives. Excellent materials and proven techniques are making
      the transition from traditional metallic restorations easier and more
      predictable. With this article, the authors aim to help dentists gain confidence
      in their technique and enable them to provide this service for their patients.

PMID- 11575017
TI  - Simulated shape design. Helping patients decide their esthetic ideal.
AB  - BACKGROUND: Esthetic care is changing dentistry from a need-based to a want-based
      practice. Patients are asking for esthetic treatment, and clinicians are
      retooling their practices to satisfy this need. One important part of providing
      esthetic dentistry is ensuring that the patient is as well-informed as possible
      about treatment outcomes. DESCRIPTION OF TECHNIQUE: This article describes a tool
      dentists can use to show patients potential tooth sizes, shapes and arrangements
      before carrying out treatment. Simulated shape design, or SSD, is a reversible
      method of demonstrating potential esthetic outcomes that involves creating trial
      restoration shapes and placing them over a patient's teeth. SSD is a simple
      technique that any dentist can perform. In essence, the technician makes new
      tooth shapes in wax, the dentist places these in the patient's mouth and the
      patient evaluates them. The dentist then makes modifications in the SSD, which he
      or she reports to the technician. CLINICAL IMPLICATIONS: With the decisions of
      shape, arrangement and size made at chairside, the whole flow of esthetic
      treatment can be handled smoothly. Preparations can be cut more accurately to
      better support the restorative material; decisions can be made to open or not
      open the contacts; and shapes can be agreed on in the earliest stage of
      evaluation, then duplicated faithfully in the provisional and final restorations.
      There are no surprises for the patient, the dentist or the technician. Both the
      esthetic (smile design) and functional elements (anterior guidance) of the
      restoration can be checked with SSD. SSD could become the standard in determining
      whether or not to proceed with esthetic treatment.

PMID- 11575018
TI  - Clinical performance of resin-modified glass ionomer cement restorations in
      primary teeth. A retrospective evaluation.
AB  - BACKGROUND: The authors retrospectively evaluated the clinical performance of one
      resin-modified glass ionomer cement as a restorative material in Class I, Class
      II, Class III and Class V restorations in primary teeth. METHODS: A total of 306
      patients who had received a total of 864 resin-modified glass ionomer
      restorations, which had been in their mouths for a minimum of three years, were
      included in this evaluation. The authors assessed the clinical observations
      recorded in patients' records and used bitewing radiographs to assess Class II
      restorations. RESULTS: The authors found an overall restoration success rate of
      93.0 percent, with Class I restorations having a 92.6 percent success rate, Class
      II restorations having a 93.3 percent success rate, Class III restorations having
      a 100 percent success rate, and Class V restorations having a 98.0 percent
      success rate. CONCLUSIONS: The resin-modified glass ionomer cement functioned
      well as a Class I, Class II, Class III and Class V restorative material in
      primary teeth. CLINICAL IMPLICATIONS: Resin-modified glass ionomer restorative
      cement is a durable and reliable material to use for Class I, Class II, Class III
      and Class V restorations in primary teeth. Therefore, dentists have a proven
      alternative to silver amalgam and resin-based composite for primary tooth
      restoration.

PMID- 11575019
TI  - Clinical evaluation of two one-bottle dentin adhesives at three years.
AB  - BACKGROUND: The method currently used to adhere resin to dentin involves etching,
      priming and bonding. Many commercial adhesives now combine priming and bonding
      functions in a single solution, and these are frequently called one-bottle
      adhesives. The purpose of this study was to compare the 36-month clinical
      performance of two commercial one-bottle adhesives. METHODS: The authors enrolled
      33 patients with noncarious cervical lesions in the study. A total of 101 lesions
      were restored with either a filled, ethanol-based adhesive (OptiBond Solo, SDS
      Kerr) or an unfilled, acetone-based adhesive (Prime & Bond 2.1, Dentsply Caulk)
      and a hybrid resin-based composite. Enamel margins were not beveled, and no
      mechanical retention was placed. The restorations were evaluated at baseline and
      six months, 18 months and 36 months after placement using modified Cvar/Ryge
      criteria. RESULTS: The retention rates at 36 months were 93.3 percent for the
      ethanol-based adhesive and 89.4 percent for the acetone-based adhesive. The
      difference in retention rates was not statistically significant. In both groups,
      12 percent of the retained restorations had marginal staining, but no recurrent
      caries was detected around any restoration. Other restoration characteristics
      such as marginal adaptation and color match remained excellent three years after
      placement. CONCLUSIONS: The performance of both adhesives was excellent during
      this 36-month clinical trial. At the most recent recall evaluation (that is, 36
      months), the filled, ethanol-based adhesive exhibited slightly better bond
      durability, but the difference between the two materials was not statistically
      significant. CLINICAL IMPLICATIONS: The one-bottle adhesives evaluated in this
      study provided excellent clinical retention of Class V restorations without
      mechanical retention. When the materials are used properly, restorations are
      retained at a high rate during at least three years of clinical service.

PMID- 11575020
TI  - Severe oral manifestations of chronic graft-vs.-host disease.
AB  - BACKGROUND: Graft-vs.-host-disease, or GVHD, is the main cause of morbidity in
      patients who have received bone marrow transplants. Chronic GVHD, or cGVHD,
      occurs 100 days or more after the transplant procedure and may take the form of
      various oral manifestations. CASE DESCRIPTION: A 23-year-old woman received an
      allogeneic bone marrow transplant. Although prophylactic therapy was provided,
      the patient developed cGVHD. Appropriate therapy was initiated, and it received a
      good clinical response at all sites affected by cGVHD, except in the oral cavity.
      The patient received complete symptomatic relief through revised systemic
      therapy, improved oral hygiene, use of topical medications and a monitored diet.
      CLINICAL IMPLICATIONS: Effective intervention by dentists is an important part of
      increasing treatment effectiveness and improving quality of life in patients who
      received bone marrow transplants.

PMID- 11575021
TI  - Using diagnostic impressions to evaluate the fit of existing removable
      prostheses.

PMID- 11575022
TI  - Carotid artery atheromas in postmenopausal women. Their prevalence on panoramic
      radiographs and their relationship to atherogenic risk factors.
AB  - BACKGROUND: More than 60 percent of the deaths in the United States attributed to
      stroke occur in postmenopausal women. As estrogen levels decline, atherosclerotic
      lesions (that is, atheromas) develop in the region of the carotid bifurcation and
      have been implicated as the precipitating cause in the majority of these strokes.
      Atheromas often are calcified and have been detected on the panoramic radiographs
      of neurologically asymptomatic male veterans; however, similar studies have not
      been conducted among female veterans. METHODS: The authors assessed panoramic
      radiographs and medical records of 52 neurologically asymptomatic female veterans
      (mean age, 70.4 years), with a history of amenorrhea of more than 12 months'
      duration, for atheromas and risk factors associated with atherosclerosis.
      RESULTS: The radiographs of 16 subjects (31 percent) exhibited atheromas located
      in the neck about 2.0 centimeters inferior and posterior to the angle of the
      mandible. These findings were confirmed in all instances by the presence of
      atheromas on anteroposterior cervical spine radiographs. The medical histories of
      these subjects were heavily laden with atherogenic risk factors (hypertension, 94
      percent; body mass index of 27 to 29.9 [characterized as overweight], 25 percent;
      body mass index of 30 or higher [characterized as obese], 25 percent; smoking
      more than 15 pack-years, 38 percent; hyperlipidemia, 69 percent; type 2 diabetes
      mellitus, 21 percent). Hypertension was significantly associated with the
      presence of atheromas. CONCLUSIONS: Some neurologically asymptomatic women at
      high risk of developing stroke can be identified in the dental office via
      panoramic radiography. Women whose X-rays show calcified carotid artery atheromas
      are almost always hypertensive and have medical histories heavily laden with
      other atherogenic risk factors. CLINICAL IMPLICATIONS: Dentists should refer
      patients with such calcifications to an appropriate physician for further
      evaluation and treatment.

PMID- 11575023
TI  - The impact of insurance coverage on children's dental visits and expenditures,
      1996.
AB  - BACKGROUND: Health insurance coverage has been shown to relate positively with
      the use of dental services. The purpose of the authors' study was to describe the
      level of dental coverage among U.S. children and to assess the impact of dental
      coverage on children's use of dental services and expenditures for dental care.
      METHODS: The focus of these analyses is on dental care coverage, use and
      expenditures for U.S. children during 1996. National estimates are provided for
      the population with dental coverage, the population with a dental visit, and mean
      total expenditure for each of several socioeconomic and demographic categories
      during 1996 using data from the Medical Expenditure Panel Survey. RESULTS: Fifty
      two percent of children younger than 18 years of age had private dental coverage
      during 1996. Approximately 56 percent of children in families with a poverty
      status level of 133 percent of the federal poverty level or below were covered by
      Medicaid during 1996. Fifty-six percent of children with private coverage had
      made at least one dental visit, compared with 28 percent of noncovered children.
      Twenty-eight percent of children covered by Medicaid had made at least one dental
      visit compared with 19 percent of noncovered children. CONCLUSION: Medicaid
      dental coverage seems to have had a lesser effect on the likelihood of a child's
      having a dental visit than had private coverage. Improving oral health for poorer
      children may depend partly on improving the design of Medicaid dental coverage
      programs. PRACTICE IMPLICATIONS: By understanding these analyses, practitioners,
      advocates and policymakers will be better positioned to provide care, improve
      access and better meet the needs of all American children.

PMID- 11575024
TI  - National Institutes of Health Consensus Development Conference statement.
      Diagnosis and management of dental caries throughout life, March 26-28, 2001.
AB  - OBJECTIVE: To provide health care providers, patients and the general public with
      a responsible assessment of currently available data regarding the diagnosis and
      management of dental caries throughout life. PARTICIPANTS: A nonfederal,
      nonadvocate, 13-member panel representing the fields of dentistry, epidemiology,
      genetics, medicine, oral biology, oral radiology, pathology, periodontics, public
      health, statistics and surgery, as well as a public representative. In addition,
      31 experts in these same fields presented data to the panel and to a conference
      audience of approximately 700. EVIDENCE: Presentations by experts; a systematic
      review of the dental research literature provided by the Agency for Healthcare
      Research and Quality; and an extensive bibliography of dental caries research
      articles, prepared by the National Library of Medicine. Scientific evidence was
      given precedence over clinical anecdotal experience. CONSENSUS PROCESS: Answering
      predefined questions, the panel drafted a statement based on the scientific
      evidence presented in open forum and the scientific literature. The draft
      statement was read in its entirety on the final day of the conference and
      circulated to the experts and the audience for comment. The panel then met in
      executive session to consider these comments and released a revised statement at
      the end of the conference. The statement was made available on the World Wide Web
      at "consensus.nih.gov" immediately after the conference. This statement is an
      independent report of the panel and is not a policy statement of the National
      Institutes of Health or the federal government.

PMID- 11575025
TI  - The credibility of dentists.

PMID- 11575026
TI  - A setback for collective bargaining.

PMID- 11575027
TI  - The school-police partnership. Identifying at-risk youth through a truant
      recovery program.
AB  - A substantial amount of research has established that truancy is a consistent at
      risk indicator of future criminality. This article studies the experiences of 178
      juveniles targeted by the Truant Recovery Program, a collaborative and
      nonpunitive school-law enforcement effort, and considers questions regarding its
      impact through examination of juvenile justice and school information in the
      years before and after the truancy sweep. In particular, the article suggests
      that intensive cooperative efforts between school and police may be effective in
      identifying troubled youth and raises questions about appropriate school and
      justice system responses for children who demonstrate at-risk behavior.

PMID- 11575028
TI  - A design for a relational database for the calculation and storage of greenhouse
      gas emissions.
AB  - The Intergovernmental Panel on Climate Change (IPCC) has published guidelines for
      the development of national greenhouse gas-emissions inventories and
      recommendations for collecting data necessary to calculate greenhouse gas
      emissions. Many regional and local jurisdictions will be performing inventories
      of greenhouse gas emissions and estimating the benefits of mitigation strategies
      to reduce emissions. This article advocates the development of relational
      databases to calculate and store emissions estimates based on IPCC guidelines and
      quantities of precursors of greenhouse gases. Specific examples of tables and
      queries are used to illustrate calculation methods and formulae, the choice of
      database keys, and the choice of methods for joining tables to construct queries.

PMID- 11575029
TI  - Tools for evaluating research output. Are citation-based rankings of economics
      journals stable?
AB  - Journal rankings are important for evaluating research output, for academic
      promotions, and for allocating funds. Examining the assignment of economics
      journals to different quartiles of citation-based rankings, the authors found
      that about 60% of journals remain in the same quartile and about 95% of journals
      remain in the same or move in a neighborhood quartile within 5- to 10-year
      intervals. Top journal rankings exhibit even more inertia, which is a desirable
      property for decisions on promotion, tenure, or institutional evaluation. A
      reexamination of journal assignment to different quality categories every 5 or 10
      years, therefore, suffices for practical evaluation purposes.

PMID- 11575030
TI  - Do participation rates change when active consent procedures replace passive
      consent.
AB  - Researchers face considerable ambiguity and controversy regarding the issue of
      informed consent. Decisions about consent procedures can affect study
      participation rates and prevalence estimates among specific populations. Changing
      from passive to active parental consent procedures was examined in a case study
      with an anonymous survey of sixth- through eighth-grade students' substance use.
      Four types of procedures for obtaining parental consent were examined. Results
      suggest that certain types of consent procedures can yield high levels of
      participation. This study also demonstrates that low participation rates with
      some active consent procedures can cause biases in sample characteristics and
      outcome data.

PMID- 11575031
TI  - Has our profession become its own worst enemy?

PMID- 11575032
TI  - Respect the friendly adversary.

PMID- 11575033
TI  - Change professional title for increased recognition of osteopathic physicians.

PMID- 11575034
TI  - Marketing lessons and retaining the traditional osteopathic internship.

PMID- 11575035
TI  - Knowing more than the score: providing sideline medical care coverage for
      athletic competition.

PMID- 11575036
TI  - Decline in structural examination compliance in the hospital medical record with
      advancing level of training.
AB  - A retrospective review of 115 randomly pulled hospital charts of patients
      admitted to the care of osteopathic physicians at an American Osteopathic
      Association-accredited primary care hospital revealed a significant decline in
      the frequency of structural examinations in history and physical examinations
      during a merger and relocation, as well as with increasing level of training of
      the examiner (chi 2 test, P < .001). Attending physicians completed fewer
      structural examinations (45% of their history and physical examinations) compared
      to house staff (70%) and students (92%). A follow-up anonymous survey of 100
      osteopathic physicians and students (response rate, 58%) revealed that the low
      overall frequency of structural examination completion (60%) was due primarily to
      attending physicians who considered this examination less relevant or impractical
      for their hospitalized patients. These results indicate that education on
      relevance of structural examination and manipulative treatment for acutely ill
      patients needs to be directed not only to house staff and students but also to
      attending physicians to preserve and improve the use of osteopathic principles at
      osteopathic hospitals.

PMID- 11575037
TI  - Elbow injuries in golf.
AB  - Golf is not a sport known for its high injury level; however, injuries do occur.
      Such mishaps usually involve overuse-type injuries that are more common among
      amateur golfers than among professional golfers. This article attempts to provide
      an overview of golf injuries to the elbow, with a concentration on incidence,
      proper diagnosis, adequate treatment (including rehabilitation), and prevention
      strategies. After reading this article, primary care physicians should be able to
      manage most golfing injuries to the elbow.

PMID- 11575038
TI  - Adjunctive osteopathic manipulative treatment in women with depression: a pilot
      study.
AB  - The authors assessed the impact of osteopathic manipulative treatment (OMT) as an
      adjunct to standard psychiatric treatment of women with depression. Premenopausal
      women with newly diagnosed depression were randomly assigned to either control
      (osteopathic structural examination only; n = 9) or treatment group (OMT; n = 8).
      Both groups received conventional therapy consisting of the antidepressant
      paroxetine (Paxil) hydrochloride plus weekly psychotherapy for 8 weeks. Attending
      psychiatrists and psychologists were blinded to group assignments. No significant
      differences existed between groups for age or severity of disease. After 8 weeks,
      100% of the OMT treatment group and 33% of the control group tested normal by
      psychometric evaluation. No significant differences or trends were observed
      between groups in levels of cytokine production (IL-1, IL-10, IL-2, IL-4, and IL
      6) or in levels of anti-HSV-1, anti-HSV-2, and anti-EBV antibody. There was no
      pattern to the osteopathic manipulative structural dysfunctions recorded. The
      findings of this pilot study indicate that OMT may be a useful adjunctive
      treatment for alleviating depression in women.

PMID- 11575040
TI  - A research program for the osteopathic profession, our great and only hope.

PMID- 11575039
TI  - Dual components of optimal asthma therapy: scientific and clinical rationale for
      the use of long-acting beta-agonists with inhaled corticosteroids.
AB  - The authors describe the scientific rationale for using an inhaled corticosteroid
      with an inhaled long-acting beta 2-agonist. They discuss the clinical trials
      demonstrating that using an inhaled corticosteroid with an inhaled long-acting
      beta 2-agonist provides greater overall asthma control compared with increasing
      the dose of inhaled corticosteroid. In addition, they review the clinical trials
      comparing the addition of a leukotriene modifier to an inhaled corticosteroid
      versus using an inhaled corticosteroid with an inhaled long-acting beta 2
      agonist. Discussion also includes descriptions of trials showing reduced
      exacerbations of asthma when using an inhaled corticosteroid with an inhaled long
      acting beta 2-agonist. Finally, the authors provide evidence for the ability to
      detect deteriorating asthma when using an inhaled corticosteroid with an inhaled
      long-acting beta 2-agonist, and they provide a comparison of salmeterol and
      formoterol, two long-acting beta 2-agonists.

PMID- 11575041
TI  - Recent discoveries in assessment of coronary heart disease: impact of vascular
      mechanisms on development of atherosclerosis.
AB  - Until recently, arterial stenosis and occlusion due to buildup of atherosclerotic
      plaque were recognized as the primary causes of coronary heart disease (CHD).
      Currently, CHD is viewed as a lifelong process of endothelial inflammation,
      thrombosis, and plaque instability and rupture. Lifestyle modification is an
      important first step in prevention of CHD, but even those patients who are the
      most committed to following a healthy diet and lifestyle frequently require the
      addition of drug therapy to further reduce risk. The 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitors (statins) reduce risk by lowering low-density
      lipoprotein cholesterol levels, as well as by stabilizing plaques, restoring
      endothelial function, and counteracting oxidative and inflammatory processes.
      Angiotensin-converting enzyme inhibitors also have antiatherogenic properties.
      Early, aggressive lipid intervention is the key to primary and secondary
      prevention of CHD.

PMID- 11575042
TI  - Managing borderline levels of risk for coronary heart disease: two illustrative
      case presentations.
AB  - Much has been learned about preventing and treating coronary heart disease (CHD)
      since publication of the National Cholesterol Education Program (NCEP) Adult
      Treatment Panel II (ATP II) guidelines in 1993. Even with the recent release of
      the ATP III guidelines, clinical decision making has become increasingly complex
      as a result of the tremendous volume of new data, and because many common patient
      types do not fit precisely into the defined risk categories. The case studies
      presented here illustrate how data from recent trials and the clinician's
      judgment should be weighed together in the decision to initiate cholesterol
      lowering therapy in patients with borderline risk levels, as part of a strategy
      for primary and secondary prevention of CHD.

PMID- 11575043
TI  - Preventive strategies for reducing coronary heart disease-related morbidity and
      mortality in patients with multiple risk factors.
AB  - Based on epidemiologic and clinical evidence, the National Cholesterol Education
      Program Adult Treatment Panel has identified low-density lipoprotein cholesterol
      as the primary target for lipid intervention to promote the reduction of high
      cholesterol through increased awareness and aggressive management of
      cardiovascular risk factors. These guidelines provide the basis for management of
      multiple risk factors and applied intervention using diet, exercise, and drug
      therapy to lower cholesterol levels. Data from primary- and secondary-prevention
      trials strongly support the rationale for aggressive therapy with 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitors (statins) to significantly reduce
      morbidity and mortality from coronary heart disease.

PMID- 11575044
TI  - Peripherally inserted central catheters in children with cystic fibrosis. Eight
      cases of difficult removal.
AB  - Peripherally inserted central catheters (PICCs) are widely used in the management
      of cystic fibrosis (CF) in children and adults. The authors present a collection
      of eight case reports of patients with CF in whom removal of PICCs was difficult,
      including two PICCs that required surgical removal. The cases were observed in a
      regional pediatric CF unit in the United Kingdom. Possible etiology and
      strategies that can be used to achieve catheter removal are discussed.

PMID- 11575045
TI  - Ethical issues in genetic testing. The experiences of one family diagnosed with
      an inherited cancer syndrome.
AB  - This article describes selected ethical issues faced by members of a family with
      genetic predisposition to the cancer syndrome multiple endocrine neoplasia type
      2a. The bioethical principles of autonomy, nonmaleficence, beneficence, and
      justice are the moral guides for nurses and other health professionals, who may
      apply them to help patients, family members and peers resolve ethical issues and
      moral dilemmas. Sometimes, however, issues that are morally problematic cannot be
      settled by simply referring to standards of practice and bioethical norms. In
      these cases all stakeholders must struggle together to resolve the conflict.

PMID- 11575046
TI  - Haploidentical transplantation. Importance of histocompatibility testing and
      chimerism studies in allogeneic bone marrow/stem cell transplantation.
AB  - The transplantation of hematopoietic stem cells is sometimes the only treatment
      option for certain types of malignancies and hematological disorders. The best
      way to ensure a positive outcome from this type of procedure is to secure an
      identical human lymphocyte antigen-matched donor or use an autologous graft. This
      article reviews the indications for transplantation, the recipient and donor
      selection process, and posttransplant follow-up. The advantages of using
      haploidentical donors and the typing process also will be discussed.

PMID- 11575048
TI  - Nurse-driven interventional technology. A cost and benefit perspective.
AB  - The article describes the institution of a cost-effective, efficient, nurse
      driven advanced intervention for peripherally inserted central catheter (PICC)
      placement using microintroducers and venous ultrasound. Obstacles are identified
      and steps taken to overcome these obstacles are described. The importance of
      gathering support from key groups including the i.v. Team is discussed. Results
      showed a significant cost savings and additional benefits. Nurse-driven
      interventional technology is a positive advancement in the placing of PICCs.

PMID- 11575047
TI  - Pharmacological update on new infusion drugs.
AB  - Ongoing clinical research and development of new infusion medications can
      challenge the infusion specialist's knowledge base in daily practice. This
      article reviews new and soon-to-be marketed infusion drugs, with an emphasis on
      biopharmaceuticals. The author also discusses mechanisms of action, drug
      interactions, side effects, and infusion specialist interventions for safe
      administration of these medications.

PMID- 11575049
TI  - Relationship between peripheral intravenous catheter Dwell time and the
      development of phlebitis and infiltration.
AB  - The purpose of this study was to evaluate whether lengthening the dwell time of
      peripheral i.v. catheters from 72 hours to 144 hours resulted in increased rates
      of phlebitis and/or infiltration. The study was conducted in medical/surgical
      units at a 110-bed teaching hospital with an i.v. team. Kaplan-Meier estimates of
      the success and failure and conditional failure probabilities were calculated for
      phlebitis and infiltration scores. Log rank tests were used to test for an
      association between the covariates and the time until failure. Drug irritation
      was the most significant predictor of phlebitis and infiltration rates in this
      study. The total difference in the estimated failure rates for the catheter
      lasting 6 days versus a new catheter inserted for another 3 days is 1.3%. Because
      the conditional failure probability estimates for days 4, 5, and 6 are slightly
      higher than for days 1, 2, and 3, consideration may be given to extending the
      dwell time of a peripheral i.v. catheter beyond 72 hours under certain
      circumstances.

PMID- 11575050
TI  - Differences in dietary patterns of nonsmoking adults married to smokers vs.
      nonsmokers.
AB  - PURPOSE: To compare dietary intakes of nonsmoking adults married to smokers or
      nonsmokers. DESIGN: Respondents to the U.S. Department of Agriculture's
      Continuing Survey of Food Intakes by Individuals (CSFII), 1994 to 1996 (response
      rate = 76.1% for 2 days of dietary intake). Nonsmoking adults aged 18 and older
      were grouped according to the smoking status of their spouse. SETTING: In-home
      interviews in all 50 states and Washington, D.C. SUBJECTS: The selected sample
      included 757 men and 754 women who were married to nonsmokers, and 197 men and
      262 women who were married to smokers. MEASURES: Selected demographic variables,
      food group servings, food energy, and densities of selected nutrients were
      compared using chi 2 and analysis of covariance. RESULTS: Men and women married
      to smokers had greater (p < or = .025) energy-adjusted intakes of total and
      saturated fat but significantly lower (p < or = .05) energy-adjusted intakes of
      fiber and vitamin A. Men married to smokers consumed significantly more (p <
      .025) energy-adjusted cholesterol and ethanol but significantly less calcium (p =
      .026); women married to smokers consumed significantly less (p = .014) energy
      adjusted folate. Men married to smokers consumed significantly more (p < or =
      .05) alcoholic beverages, coffee, and soft drinks; women married to smokers
      consumed significantly less water (p = .014) but more cheese and table sweeteners
      (p < or = .05). CONCLUSIONS: Nonsmoking men and women who were married to smokers
      had compromised dietary intakes. Nonsmoking men whose wives smoked, in
      particular, had unhealthy diets due to elevated intakes of fat and cholesterol
      and low intakes of vitamin A, calcium, and fiber. Health professionals should
      continue to provide tobacco cessation instruction and dietary guidance, but also
      be aware of at-risk patients' immediate family members who likely share an
      increased risk of disease because of poor diet quality and exposure to
      environmental tobacco smoke.

PMID- 11575051
TI  - The cardiovascular health impact of an incentive worksite health promotion
      program.
AB  - PURPOSE: We examined the cardiovascular health profiles of benefit-eligible
      hospital employees who participated in an incentive screen program for 4 years.
      We also determined if cardiovascular health changes differed between participants
      (CHAP) who enrolled in structured follow-up risk reduction programs (CHAPplus)
      compared with those who chose less formal options (CHAPonly). METHODS: CHAP
      consisted of cardiovascular screens, results counseling, and encouragement to
      participate in education and behavioral support programs. After adjusting for
      gender, medication use, and baseline levels of adiposity and physical activity,
      cardiovascular health changes were tested with repeated-measures analysis of
      covariance (ANCOVA) among CHAP participants and by CHAP type. RESULTS: CHAP 4
      year members (n = 278) were generally healthy and mostly women (87%) with an
      average age of 40.6 +/- .5 years at baseline. Despite increases in overall (p =
      .034) and central adiposity (p = .001), cardiovascular health improvements were
      found for the total cholesterol/high-density lipoprotein ratio (TCHOL/HDL; p =
      .007), low-density lipoprotein (p = .009), and blood glucose (p = .018) among 4
      year CHAP members. CHAPonly employees showed greater improvements in most
      cardiovascular health indicators than CHAPplus participants, although these
      differences did not achieve statistical significance. DISCUSSION: Cardiovascular
      health improvements were associated with long-term participation in a hospital
      worksite incentive screen program. The cardiovascular health benefits tended to
      be greatest for CHAP employees who chose informal follow-up risk reduction
      options (CHAPonly) than those who enrolled in structured programs (CHAPplus).

PMID- 11575052
TI  - The impact of an incentive-based worksite health promotion program on modifiable
      health risk factors.
AB  - A health promotion program consisting of an annual health screening and financial
      rebates for good health practices was offered to all 2540 employees of Salt Lake
      County in Utah. Changes in health risks were measured for the 304 full time
      employees who participated in assessments for four years. Significant
      improvements were seen in body fat, cholesterol, systolic and diastolic blood
      pressure, seat belt use, and overall physical health among the high risk group
      and the low risk group. There was a net increase in the number of people in the
      high risk group over the four year period.

PMID- 11575053
TI  - Effect of health lifestyle pattern on dietary change.
AB  - PURPOSE: To examine the effect of lifestyle on the effectiveness of a low
      intensity dietary intervention. DESIGN: A secondary data analysis was performed
      using data from the Eating Patterns Study, a randomized controlled trial that
      found that self-help materials with physician advice was effective in changing
      dietary intake and behavior. SETTING: Primary care clinics in a large health
      maintenance organization. SUBJECTS: A total of 2111 patients with a routine
      scheduled appointment with their primary care physicians. MEASURES: Participants
      were grouped into one of six health lifestyle patterns based on similarities in
      baseline measures of alcohol intake, smoking, diet quality, and exercise. Within
      each lifestyle pattern, changes from baseline in usual fat and fiber intake
      (based on a food frequency) and a fat and fiber behavior score were compared at 3
      months and 12 months for intervention vs. control participants. INTERVENTION:
      Self-help materials delivered by a physician with advice to change diet. RESULTS:
      Intervention participants in the fitness lifestyle group made the largest changes
      relative to controls for each dietary outcome at 3 and 12 months. For
      intervention participants defined by their alcohol intake or current smoking,
      either no changes in diet were observed compared with controls, or early changes
      were not sustained over time. Intervention-control comparisons within the
      remaining lifestyle patterns showed smaller dietary changes compared with the
      fitness lifestyle. This finding was similar to previously published results.
      CONCLUSIONS: This randomized controlled trial had limited power to detect
      subgroup differences; however, these results suggest that lifestyle patterns may
      be useful in the development of effective, targeted interventions to change
      behavior.

PMID- 11575054
TI  - A new measure for assessing the physical activity behaviors of persons with
      disabilities and chronic health conditions: the Physical Activity and Disability
      Survey.
AB  - PURPOSE: Assess the psychometric properties of the Physical Activity and
      Disability Survey (PADS), a new physical activity measure for persons with
      disabilities and chronic health conditions. DESIGN: Cross-sectional and pre-post
      designs were employed. SETTING: A Midwestern university fitness center. SUBJECTS:
      Participants were 103 individuals with disabilities and/or chronic health
      conditions. MEASURES: The Physical Activity and Disability Survey (PADS), peak
      oxygen uptake (peak VO2), maximum workload (MW), and time to exhaustion (TE)
      during exercise. RESULTS: Factor analysis revealed a four-factor model that
      generally corresponded to PADS subscales. Cronbach alpha coefficients ranged from
      .67 (Exercise) to .77 (Time Indoors). Test-retest reliability (1-week interval)
      ranged from .78 (Time Indoors) to .95 (Leisure Time Physical Activity).
      Interrater reliability ranged from .92 (Household Activities) to .99 (Exercise,
      Leisure Time Physical Activity, Total Activity). Significant (p < .05)
      correlations were found between PADS subscales and absolute peak VO2 (Leisure
      Time Physical Activity, Household Activity, Total Activity), relative peak VO2
      (Exercise, Time Indoors), MW (Time Indoors, Household Activity), and TE
      (Household Activity, Total Activity). Analyses of variance revealed that, unlike
      controls, health promotion program participants evidenced significant pre-post
      gains as measured by the Exercise subscale and Total Activity score. CONCLUSIONS:
      The findings lend support for the reliability and validity of the PADS as a
      measure of physical activity of groups who are sedentary and disabled.

PMID- 11575055
TI  - Changes in health risks among the participants in the United Auto Workers-
      General Motors LifeSteps Health Promotion Program.
AB  - PURPOSE: To examine health risk changes among participants of a multicomponent
      worksite health promotion program. DESIGN: A study using health risk changes
      among health risk appraisal (HRA) participants linked to program participation
      records. Baseline risk and participation in multiple programs were examined in
      relation to risk change in multivariate models. SETTING: Worksite health
      promotion programming sponsored by the United Auto Workers (UAW) and General
      Motors (GM). SUBJECTS: Active employees (12,984) who voluntarily participated in
      an HRA in each of two program years. INTERVENTION: The nationwide program was a
      mailed HRA and a 1-800 nurse line. A pilot program (implemented in two cities)
      added screening, wellness programs, a materials resource, and, for high risk
      participants, health coaching and vouchers for medical office visits. MEASURES:
      Using 13 selected health risk factors from the HRA, changes in overall health
      risks were measured as program outcomes in three ways: one-directional, net, and
      risk status change. RESULTS: A greater decrease in the number of health risks was
      observed with increased program participation. The decrease was significantly
      related to the number of baseline risk factors and eligibility for high risk
      programs. Associated with program participation, the number of people at low risk
      status increased from 70.1% to 71.3% at year 2 among nationwide participants and
      from 52.4% to 58.9% among pilot participants. CONCLUSIONS: Participation was
      associated with a significant impact on health risk. Baseline risk of
      participants and eligibility for high risk programs were necessary factors to
      control when measuring program effects on health risk changes.

PMID- 11575057
TI  - The use of patient registers to estimate migration.
AB  - This article presents information discussed at the recent regional seminars on
      population statistics. It describes a new data source for estimating internal
      migration between local and health authorities in England and Wales, discusses
      the way that the data have been collected and processed, and how limitations in
      the raw data have been addressed. It then goes on to explain the way that the new
      internal migration estimates have been used in the calculation of population
      estimates for local and health authorities. This is a change to the method of
      estimating migration in the calculation of population estimates.

PMID- 11575056
TI  - Social inequalities in later life: the socio-economic position of older people
      from ethnic minority groups in Britain.
AB  - There are now nearly a quarter of a million individuals aged 60 years or over
      belonging to ethnic minority groups living in Britain. As the ethnic minority
      groups in Britain continue to age, information regarding their circumstances in
      later life will be of increasing importance for the development of appropriate
      services and policy. This article uses data from the General Household Survey
      (1991-96) to investigate the household living arrangements, lifestyle, socio
      economic status, economic resources and experience of multiple deprivation in
      later life amongst older people from ethnic minority groups in Britain. The
      findings indicate that there are significant differences both between and within
      ethnic minority groups in access to material and social resources, which need to
      be taken into account by policy makers and planners.

PMID- 11575058
TI  - Fragmented life courses: the changing profile of Britain's ethnic populations.
AB  - This article describes the potential of the Longitudinal Study to analyse
      different ethnic groups by broad period of entry. This is illustrated with the
      use of one variable (childlessness), but could be the basis for further
      analytical work on other variables. Each group has a unique demographic profile,
      which is largely explained by its migration history. Migration influences
      important life course transitions. Differences between more established residents
      (present in 1981 and 1991) and less established residents (present in 1991 only)
      imply that generalisations for the entire ethnic group or future generations
      should not be made.

PMID- 11575059
TI  - It isn't something to yodel about, but it exists! Faeces, nurses, social
      relations and status within a mental hospital.
AB  - In medical settings, emotion-provoking work creates a hierarchy among health care
      professionals. "Lower" emotions like disgust, contempt or aversion that are
      evoked by "body work" with elderly patients often remain invisible, but they play
      an important role in morality and shape the social relations between the patients
      and the professionals. With the help of ethnographic data from the nursing wards
      of a mental hospital, the author shows how feelings about excrement are
      determined not only by their nature, but also by the nature of the relationships
      among the nurses and the relationships between the nurses and the elderly
      patients. Body care and the emotions that are evoked are connected to morality
      and moral care. Dealing with bodily and moral "dirt" gives nurses a special
      position within the hospital as a whole, which will have effects on the care for
      elderly.

PMID- 11575060
TI  - Correlates of psychotropic drug use in the elderly compared to adults aged 18-64:
      results from the Quebec Health Survey.
AB  - This study documents correlates of psychotropic drug use among older adults and
      compares the results observed in this group to those observed in individuals aged
      18-64. A multivariate logistic regression analysis using data from the Quebec
      Health Survey (1992-1993) was employed to study predisposing and facilitating
      factors of this behavior. Results showed that 22% of the elderly reported having
      used anxiolytics, sedatives or hypnotics during the two days preceding the
      survey, compared to 4.9% of the respondents aged 18-64. Combining both samples,
      perceived health status, physical functional status, and health services
      utilization for psychological distress symptoms were the main health factors
      associated with psychotropic drug use. A significant difference was observed
      between the two age groups with regard to the association between the
      respondents' health status and the use of anxiolytics, sedatives or hypnotics.
      When the effect of other explanatory factors was controlled, older adults in poor
      health used anxiolytics, sedatives or hypnotics 2.21 times more than individuals
      aged 18-64 with a similar health condition, whereas older adults in good health
      used these drugs 7.49 times more than healthy individuals aged 18-64.
      Furthermore, after controlling for the effect of the respondents' physical and
      psychological health status, our results showed that more women than men used
      psychotropic drugs (OR = 1.57; 99% CI = 1.26-1.94). Low-income respondents were
      also more likely to report using these medications (OR = 1.53; 99% CI = 1.22
      1.90). These results were interpreted as supporting the socio-cultural hypothesis
      of psychotropic drug use, which suggests that the prescribing and utilization of
      psychotropic drugs is influenced not only by symptoms but also by the social
      characteristics of individuals. It is suggested that future research may
      contribute to a better understanding of psychotropic drug utilization in the
      older adult community-dwelling population by examining consumers' attitudes and
      health care providers' social values concerning the appropriateness of this
      behavior.

PMID- 11575061
TI  - Mental health, stress correlates and psychotropic drug use or non-use among aged
      caregivers to elders with dementia.
AB  - The goal of the study was to compare caregivers who used psychotropic drugs with
      caregivers who were non-users in order to pinpoint differences in coping styles
      between the two groups. We performed a secondary analysis of a study on the
      stress and psychological well-being of persons caring for relatives with
      dementia. We compared elderly caregivers, as either psychotropic drug users (n =
      61) or non-users (n = 133), over various psychosocial characteristics relating to
      the care-giving context. Results reveal that users, as compared to non-users
      were: (a) more disturbed (appraised a greater stress) by the relative's
      dysfunctional behaviours, after controlling for the frequency of the behaviours;
      and (b) experienced more conflict during interpersonal interactions, although
      their appraisal of self-satisfaction with formal and informal support to their
      care-giving activities did not differ significantly. Strikingly, users combined
      and called on a greater number of problem-focused and emotion-reducing coping
      strategies than did non-users. They more frequently used affective regulation and
      information seeking coping styles. Stress-related measures (especially stress
      appraisal and conflict) contributed more to the variation in mental distress of
      users than of non-users. Results provide a theoretical and empirical rationale
      for therapeutic interventions such as the cognitive behavioural approach.

PMID- 11575062
TI  - Use of drugs by Old Age Psychiatrists in the treatment of psychotic and
      behavioural symptoms in patients with dementia.
AB  - The objective was to elicit the prescribing practises of Old Age Psychiatrists in
      the UK in the treatment of psychotic and behavioural symptoms in patients with
      dementia. A structured questionnaire was sent to all Old Age Psychiatrists in the
      United Kingdom. Respondents were questioned regarding their use of both typical
      and atypical antipsychotics and the most common dosages prescribed. Information
      was sought about usage of depot medication and dosages; use of alternative or
      adjunctive medications to antipsychotics and use of parenteral medication for
      acute management of agitation. The most commonly used antipsychotic to treat
      psychotic symptoms was haloperidol, and thioridazine to treat behavioural
      symptoms. A wide range of dosages was used. Use of depot medication was common,
      with flupenthixol decanoate being the most frequently used. Most respondents use
      at least one of the atypical antipsychotics, risperidone being most popular. Use
      of other psychotropic medication used as alternatives to antipsychotics or
      adjunctives in the treatment of behavioural symptoms was common, the most popular
      being trazodone. Of the respondents, 62.7% use parenteral medication for the
      acute management of agitation, the most popular drug being haloperidol. The
      typical antipsychotics are still the most commonly used despite the reputed
      better safety profile of the atypicals. There was wide variation in the dosages
      prescribed. Use of psychotropics other than phenothiazines was common. More
      research is needed into the use of psychotropic medication for dementia and there
      is need for consensus in this area. Forming an expert group may be the best way
      to create uniformity of prescription.

PMID- 11575063
TI  - Social comparison in Chinese older adults.
AB  - Depression is quite common among the elderly members of Hong Kong Chinese
      society. This study examined the role of social comparison in the relationship
      between depressive symptoms and four key life domains including: physical health,
      financial situation, relationships with adult children, and social support from
      friends. The respondents were 411 people aged 60 years or older from a survey of
      a representative community sample of the elderly population in Hong Kong. Using
      multiple regression models, the authors found that social comparison mediated the
      effect of support from friends on depressive symptoms and social comparison was
      the partial mediator in the linkage between financial strain and depressive
      symptoms. Moreover, social comparison also moderated the effect of physical
      health and support from friends on depressive symptoms. Lastly, we found that
      self-efficacy and self-esteem were moderators in the relationship between
      depressive symptoms and all four key life domains including physical health,
      financial situation, relationship with adult children, and social support from
      friends, whereas sense of control over physical health and sense of control over
      support from friends moderated the effect of social comparison on physical health
      and support from friends, respectively, on depressive symptoms.

PMID- 11575064
TI  - The needs and mental health of older people in 24-hour care residential
      placements.
AB  - At present one in five men and one in three women who reach the age of 65 in the
      UK today can expect to require 24-hour residential care. They are assessed
      according to needs as to the type of placement that is required. Little is known
      about the changing needs and symptoms of residential clients over 65 with mental
      health problems. The needs and neuropsychiatric symptoms of older people living
      in residential, nursing and hospital settings were assessed by standardized
      questionnaire. Seventy-seven residents were interviewed using the Camberwell
      Assessment of Needs for the Elderly (CANE) and the Neuropsychiatric Inventory
      (NPI). The mean CANE for all settings was high. The highest mean CANE was for a
      residential home and the lowest for a hospital setting. Similar settings had
      varying NPI and CANE. The data suggests that once placed, subjects needs and
      neuropsychiatric symptoms do not remain static. It may make both clinical and
      fiscal sense to reassess subjects. The development of more residential settings,
      which allow flexibility of degree of care, is recommended.

PMID- 11575065
TI  - Measuring the well-being of people with dementia living in formal care settings:
      the use of Dementia Care Mapping.
AB  - Over the years there have been advances in the quality of care provision for
      people with dementia. How to measure the impact of care on the person with
      dementia has challenged researchers as, until recently, no evaluation tool
      offered a comprehensive overview of the behaviour patterns and well-being of
      persons with dementia. Dementia Care Mapping (DCM) is a tool used by care
      practitioners and researchers to capture both the process (behaviours) and
      outcome (well-being) of care and is therefore of use as a tool to evaluate
      quality of care. This study aims to assess, through DCM, the experience of
      dementia care provision in residential and nursing homes in two voluntary
      organizations in England. The data illustrates similarities in the well-being and
      behaviour patterns of 76 persons with dementia living in six care settings
      throughout England. Examples of instances when people with dementia were "put
      down" and when well-being was enhanced, are outlined. The homes in the study were
      meeting the physical care but not the broader psychosocial care needs of the
      observed residents. The action taken by the organizations as a result of the DCM
      evaluations is summarized.

PMID- 11575066
TI  - Worry content reported by older adults with and without generalized anxiety
      disorder.
AB  - This study investigated worry content in older adults with and without
      generalized anxiety disorder (GAD). This is an important topic of research, where
      findings may promote improved recognition and treatment of this disorder in late
      life, as well as provide information about the nature of worry across the
      lifespan. Worry content was compared for 44 older adults diagnosed with GAD and
      44 normal control (NC) volunteers matched for age, gender, and ethnicity. Results
      indicated that older adults with GAD reported a wider variety of worry topics
      than did NC participants. However, there were no differences in worry content
      patterns between older adults with and without GAD. These results suggest that
      pathological worry in later life is not uniquely defined by content, and
      implications of these findings for assessment and treatment of GAD in older
      adults are discussed. Worry content reported by older adults also was compared
      with previously published younger adult worry content data. Age differences in
      worry content were found in both the clinical and non-clinical groups in patterns
      that were generally consistent with common age-related developmental changes.
      Directions for future research of worry across the lifespan are proposed.

PMID- 11575067
TI  - Accuracy of self-reported stroke among elderly veterans.
AB  - The objective was to use secondary analysis of prevalence data from a prospective
      cohort study to ascertain the accuracy of self-reported stroke among veterans.
      The study comprised a community-dwelling population of 88 elderly veterans (from
      five counties in the Northern Piedmont of North Carolina, USA) who received
      health care at the local Veterans Health Administration (VHA) medical center and
      were respondents at the North Carolina site of the NIH-funded Established
      Populations for Epidemiologic Studies of the Elderly (EPESE) project. Self-report
      of stroke from the baseline interview of the EPESE project; and occurrence of
      stroke as verified by the national VHA hospital discharge database and the
      patients' medical records was measured. Results showed that self-report of stroke
      had a sensitivity of 86% and a specificity of 100%; the predictive value of a
      positive report was 100%. Veterans' self-reports of stroke are sufficiently
      accurate to use in preliminary epidemiological studies and health services
      research of cerebrovascular disease.

PMID- 11575068
TI  - The moderating effect of aggressive problem behaviors in the generation of more
      positive attitudes toward nursing home residents.
AB  - This study examined the ability of a social history intervention to generate more
      positive attitudes toward nursing home patients, and to increase staff members'
      perceived rewards of care-giving. In contrast to prior studies, residents'
      problem behaviors were examined as potential moderators in the relationship.
      Forty-three staff members participated in an experimental, 3 (informational
      condition: social history, medical, control) x 2 (time: pre-test, post-test)
      within-subjects factorial design that employed newly admitted residents as target
      patients. Findings showed that the social history intervention alone did not
      generate more positive attitudes toward patients or greater rewards of care
      giving. Although a larger proportion of target patients manifested other problem
      behaviors with greater frequently, only aggressive problem behavior was
      associated with more negative attitudes toward patients. A post-hoc analysis
      revealed that after statistically controlling for the impact of patients'
      aggressive behavior, the social history information appeared to allow staff
      members to maintain more neutral attitudes toward patients. Considerations for
      the use of social history information in long-term care settings are addressed.

PMID- 11575069
TI  - Effects of individualized memory aids on the conversation of persons with severe
      dementia: a pilot study.
AB  - Bourgeois has shown that use of simple memory aids enhances the quality of
      conversation of persons with moderate Alzheimer-type dementia. We replicated
      Bourgeois' intervention with five people with severe dementia (Mini-Mental State
      Examination scores 0-4) and diagnoses of Alzheimer-type or vascular dementia, and
      evaluated the impact of the aids on the proportion of time participants spent on
      topic in conversation with carers. For three participants, use of the memory aid
      did not increase the proportion of time-spent on-topic. The remaining two
      participants, however, spent approximately twice as much time on-topic when using
      the aid as when conversing without it. Our results extend Bourgeois' work by
      showing that memory aids are helpful to some people with severe dementia.

PMID- 11575070
TI  - Do people with Alzheimer's disease have a disproportionate deficit in functional
      knowledge? Verbal versus motoric access to semantic memory.
AB  - Healthy elderly and Alzheimer's disease (AD) volunteers participated in four
      conditions in which they were asked to demonstrate the function and category of a
      series of objects either verbally or non-verbally. When responding verbally to
      category judgement questions, volunteers with mild-moderate AD showed levels of
      performance comparable with age and IQ-matched healthy elderly, but when
      responding verbally to questions about an item's function, they show marked
      deficits. This deficit was substantially reduced, however, when they were
      encouraged to provide the information motorically. Healthy elderly were able to
      use either mode of access without difficulty. The results of this study suggest
      that functional semantic knowledge may not be disproportionately degraded, but
      that when cognitive resources are compromised, retrieval may depend more
      critically upon mode of access. Functional information, for example, is usually
      acquired by actually using the object. Verbalizing such functions would require
      suppressing the direct (motoric) route and accessing information in a less
      familiar (verbal) form. In short, for people with AD, apparent deficits in
      semantic knowledge may reflect deficient use of unfamiliar routes of access to
      the information rather than degradation of semantic knowledge per se.

PMID- 11575071
TI  - Use of activated carbon and natural zeolite as support materials, in an anaerobic
      fluidised bed reactor, for vinasse treatment.
AB  - In Cuba, the alcohol distillation process from cane sugar molasses, produces a
      final waste (vinasse), with an enormous polluting potential and a high sulfate
      content. Applying the anaerobic technology, most of the biodegradable organic
      matter can turn into biogas, rich in methane but with concentrations of sulfide
      above 1%. The present work develops two experiences with anaerobic fluidized bed
      reactors (AFBR) using both Cuban raw material, activated carbon and natural
      zeolite, as support media, with the purpose of obtaining high organic matter
      removal rates and keeping sulfide and ammonium concentrations in the permissible
      ranges. The reactors were operated during 120 days, achieving an organic loading
      rate of 10 kg COD/m3 day, with COD removal above 70%, and a methane production of
      2 L/d. The activated carbon and natural zeolite used support materials in
      anaerobic fluidized bed reactors, and showed good results of distillery waste
      removal.

PMID- 11575072
TI  - Effect of inoculum-substrate ratio on the start-up of solid waste anaerobic
      digesters.
AB  - The anaerobic systems start-up for solid waste treatment is a fundamental step,
      especially for those with two phases. It is necessary to know both the waste
      characteristics and the inoculum conditions. The objective of this work was to
      study the inoculum-substrate ratio (ISR) influence as a previous step of the
      start-up of an anaerobic system for the solid waste digestion. During this
      research spent grain was chosen as residue, working at three different
      concentrations (7; 13 and 20% w/v), studying the ISR effect in terms of anaerobic
      degradability (AD) and specific methane productivity (SMP). The initial
      acetoclastic activities (A0) were calculated based on the equation which
      describes the methane accumulation during each test. The model constants were
      also calculated and were adjusted to the experimental data. The results showed
      that in general the ISR variation has less impact on AD than on SMP. While
      maximum AD were reached in those tests with high ISR, the greatest values of SMP
      were with the lowest values of ISR ratio. A low ISR caused a slow hydrolysis,
      although the methane production was fast. So, during the start-up of a two-phase
      anaerobic system an elevated ISR would not be necessary in order to reach a good
      AD and a good intermediate products production, because the hydrolysis and the
      VFA production must be optimised in the first phase of these systems. While in
      conventional systems, where phases are together, it is much better to optimise
      the methane production. The ISR and the SMP indicated which inoculum percentage
      would be interesting based on the objective of the whole system; methane or
      intermediate compounds (VFA) production. All this information is important during
      the conventional anaerobic reactors operation because these tests would show
      which ISRs avoid inhibition.

PMID- 11575073
TI  - Study of thermal hydrolysis as a pretreatment to mesophilic anaerobic digestion
      of pig slurry.
AB  - Feasibility of anaerobic digestion of pig slurry is dependent, among other
      factors, on the biogas production rate, which is low compared with other organic
      wastes, and on the profitable uses of surplus thermal energy produced, a limiting
      factor in warm geographical areas. The objectives of this work are determining
      whether low temperature thermal pretreatment (< 90 degrees C) improves pig slurry
      anaerobic digestion, and determining whether organic matter degradation during
      the thermal pretreatment is due to thermal phenomena (80 degrees C) or to
      enzymatic ones (60 degrees C). The thermal degradation tests showed that
      hydrolysis occurring during the thermal pretreatment is due to thermal phenomena.
      The increase in soluble substances were significantly larger at 80 degrees C than
      at 60 degrees C (both during 3 h). Two types of slurry were used in the batch
      anaerobic digestion tests. The effect of thermal pretreatment differed with the
      type of slurry: it was positive with almost non-degraded slurries containing low
      NH4(+)-N concentration, and negative (inhibition of the anaerobic digestion
      process) when using degraded slurries with high NH4(+)-N content.

PMID- 11575074
TI  - Biodegradation of 1,1,1,2-tetrachloroethane under methanogenic conditions.
AB  - Chlorinated aliphatic hydrocarbons are widely used as solvents and as
      intermediates in chemical synthesis, so they can be found in industrial
      wastewaters and released to the environment where they became a serious health
      risk due to their toxic properties and high chemical stability. Most of these
      compounds are xenobiotic and recalcitrant to biodegradation. In this article we
      report the effect of different co-substrates in the 1,1,1,2-tetrachloroethane
      (1,1,1,2-TeCA) degradation by anaerobic granular sludge, and its degradative
      pathway. Our results show that this compound is easy and rapidly biodegradable
      under methanogenic conditions, even in the absence of external electron donors.
      1,1,1,2-TeCA is equimolecularly degraded to 1,1-dichloroethene (1,1-DCE) by
      reductive dichloroelimination. 1,1-DCE is only completely biodegraded in the
      presence of lactic acid as co-substrate. Although 1,1,1,2-TeCA can be apparently
      removed by autoclaved granular sludge, the compound is not transformed but
      retained inside the granules. The primary biodegradation of 1,1,1,2-TeCE to 1,1
      DCE is a biotic process mediated by anaerobic bacteria.

PMID- 11575075
TI  - Enhanced decolourisation of acid orange 7 in a continuous UASB reactor with
      quinones as redox mediators.
AB  - The reductive biotransformation of acid orange 7 (AO7) was explored in a lab
      scale upflow anaerobic sludge blanket (UASB) reactor at low hydraulic residence
      times (HRT). A colour removal of 85% was achieved when the reactor was operated
      at a HRT of 6 hours, but decreased up to 70% when the HRT was lowered to 2 hours.
      Addition of the quinone model compound, anthraquinone 2,6-disulfonate (AQDS), as
      redox mediator, allowed for a considerably higher decolourising efficiency (> 90%
      at all the HRT evaluated). The results indicate that the use of catalytic
      concentrations of AQDS (AQDS/AO7 molar ratio about 0.01) can accelerate
      decolourising processes achieving satisfying extent of decolourisation.

PMID- 11575076
TI  - Thermophilic anaerobic digestion of methanol in UASB reactor.
AB  - A 5.1 L laboratory scale upflow anaerobic sludge bed (UASB) reactor was operated
      at 55 degrees C over 130 days in order to investigate the feasibility of treating
      methanol-containing wastewater under thermophilic conditions, focussing on start
      up and process stability. Batch assays were conducted to elucidate the most
      probable pathway for methanol conversion. The results demonstrated a good
      performance, with a chemical oxygen demand (COD) removal averaging 82% throughout
      the experiment. No significant VFA accumulation was detected in the effluent,
      even with bicarbonate concentration exceeding 20 mM. Acetate was the main
      component of the VFA at relatively low organic loading rates (OLR). At high OLR,
      the main components were propionate and butyrate. Reactor performance was hardly
      affected when the system was exposed to non-optimal conditions, i.e., temperature
      drop, overloading and no feeding. Good thermophilic granular sludge was retained
      in the reactor. Washout of biomass was not severe during the experiment. From the
      pathway analysis it could be concluded that indirect pathways play an important
      role in the methanol degradation by the cultivated consortia.

PMID- 11575077
TI  - Anaerobic oxidation of cholesterol by a denitrifying enrichment.
AB  - Sterols (e.g. cholesterol) present in wool scouring effluent represent the most
      recalcitrant fraction in anaerobic treatment. This study was conducted to examine
      the feasibility of removal of this organic load through a denitrifying post
      treatment stage. A stable cholesterol-denitrifying enrichment (CHOL-1) was
      obtained from sludge of a bench-scale upflow sludge bed (USB) denitrifying
      reactor integrated to a carbon and nitrogen removal system for sanitary landfill
      leachate. According to the amounts of cholesterol degraded and of nitrite and
      nitrogen gas formed, the capacity for complete cholesterol oxidation under
      anaerobic conditions by CHOL-1 can be assumed. Nitrite accumulation observed at a
      low C/N ratio outlines the importance of determining the optimal C/N ratio for
      adequate denitrifying reactor performance. The enrichment was partly identified
      with molecular analysis of cloned 16S rDNA sequences revealing the presence of
      two groups of bacteria belonging to the beta subclass of the Proteobacteria.
      According to analysis of sequences, it can be inferred that a yet uncultivated
      new bacterium is the one responsible for cholesterol oxidation. Results of this
      study suggest that sludge from a denitrifying reactor treating leachate is
      potentially useful in a combined anaerobic-anoxic system for degradation of
      cholesterol that remains after methanogenic treatment.

PMID- 11575078
TI  - Simultaneous organic nitrogen and sulfate removal in an anaerobic GAC fluidised
      bed reactor.
AB  - A granular activated carbon (GAC) anaerobic fluidised bed reactor treating
      vinasse from an ethanol distillery of sugar beet molasses was operated for 250
      days under three different organic loading rates. The reactor showed good
      performance in terms of organic matter removal and methane production but an
      anomalous behaviour in terms of unusual high concentrations of molecular nitrogen
      and low concentration of hydrogen sulphide in the biogas. The analysis of the
      different nitrogenous and sulphur compounds and the mass balances of these
      species in the liquid and gas phases clearly indicated an uncommon evolution of
      nitrogen and sulphur in the reactor. Up to 55% of the TKN and up to 80% of the
      sulphur disappear in the liquid phase. This is the opposite to any previously
      reported results in the bibliography. The new postulated anaerobic process of
      ammonia and sulphate removal seems to follow the mechanism: SO4 = +2 NH4+-->S +
      N2 + 4H2O (delta G degree = -47.8 kJ/mol).

PMID- 11575079
TI  - Degradation of p-nitrophenol in a batch biofilter under sequential
      anaerobic/aerobic environments.
AB  - A combined process anaerobic/aerobic in a single reactor was studied, P
      nitrophenol (PNP) was used as the model compound. During the anaerobic stage the
      target compound is modified in such a way that the intermediate product is more
      readily biodegradable by the aerobic phase. A pilot biofilter was used for the
      experiment. The biofilter was packed with a volcanic stone (puzolane) to serve as
      support to the microorganisms and it was inoculated with activated sludge. The
      microorganisms were acclimated with an initial concentration of 25 mg PNP/l
      during 75 days (25 cycles). After 230 days of operation, the reaction time of the
      cycles was reduced to 11.5 h (8 h for the anaerobic phase and 3.5 h for the
      aerobic one). The PNP was transformed to p-aminophenol (PAP) in the anaerobic
      phase, with efficiencies near to 100%. A mineralization of 100% of the PAP was
      found in the oxidative stage. Global efficiencies of PNP mineralization of 98%
      were obtained. The reaction rates were 16 mg PNP/l-h (PNP uptake), 14 mg PAP/l-h
      (PAP formation) and 20 mg/l-h (PAP mineralization).

PMID- 11575080
TI  - Biodegradation of disperse blue 79 using sequenced anaerobic/aerobic biofilters.
AB  - A sequential anaerobic/aerobic treatment process was used to biodegrade the azo
      dye disperse blue 79 (DB79). The integrated process was successfully tested and
      operated for the mineralization of the DB79 dye until a concentration of 120 mg/l
      in 96 h. In the first stage, the anaerobic biofilter biotransformed the DB79 to
      amines with efficiencies of decolorization higher than 95% in 72 h. The amines
      produced in the first stage were degraded in the aerobic biofilter with
      efficiencies of 65% in 24 h. It was observed that the use of a co-substrate on
      the anaerobic biofilter influenced the performance of the bioreactor only when
      the concentration of the DB79 was higher than 48 mg/l. It was found that the
      residual dye in the effluent of the anaerobic stage inhibits the performance of
      the aerobic microorganisms.

PMID- 11575081
TI  - Phenol degradation in horizontal-flow anaerobic immobilized biomass (HAIB)
      reactor under mesophilic conditions.
AB  - A bench-scale horizontal-flow anaerobic immobilized biomass (HAIB) reactor was
      assayed aiming to verify its potential use for phenol degradation. The HAIB
      reactor consisted of a bore-silicate tube (100 cm long; 5.04 cm diameter) filled
      with polyurethane foam matrices containing immobilized anaerobic sludge. Before
      being subjected to phenol, the reactor was fed with synthetic substrate at the
      influent chemical oxygen demand (COD) of 1,028 mg.l-1 achieving 98% of COD
      removal efficiency. Thereafter, phenol as the sole carbon source was added under
      step-increasing concentrations from 50 to 1,200 mg.l-1. Phenol degradation was
      evaluated by gas chromatographic analysis of influent and effluent samples.
      Process monitoring included determinations of pH, volatile acids, alkalinity and
      COD. The HAIB reactor was operated at a constant hydraulic detention time (HDT)
      of 12 hours. After 33 days with 50 mg/l of phenol in the influent, the reactor
      achieved 98% of COD removal efficiency. Successful phenol degradation (efficiency
      removal of 99%) occurred for influent concentrations of 100, 300, 600, 900 and
      1,200 mg.l-1 after 148, 58, 47, 29 and 7 days, respectively. The predominance of
      Methanosaeta-like, rods and methanogenic cocci could be observed in all the
      operating conditions, besides the presence of phenol oxidizing microorganisms as
      irregular rods. The results indicate that phenol degradation at very high rates
      can be accomplished in HAIB reactors containing acclimatized biomass.

PMID- 11575082
TI  - Anaerobic digestion of a nonionic surfactant: inhibition effect and
      biodegradation.
AB  - Nonionic surfactants are used worldwide in various industrial and household
      applications. Since these compounds are used in aqueous solutions, they primarily
      enter the environment through sewage and industrial wastewater treatment plants.
      The objective of this work was to evaluate the inhibitory effect of Triton X-100,
      a commercial nonionic surfactant, on the anaerobic digestion of lactose. Thus non
      ionic surfactants acts as a non-competitive inhibitor with K1 = 250 mgL-1 and a
      inhibition order of 2.4. Nonetheless if give enough time the sludge was able to
      degrade 79% of Triton at 0.1 gL-1 d-1 in a UASB reactor. An activity test of this
      sludge showed that Triton inhibited the acetogenic (both propionic and butyric)
      and acetoclastic activities, while there were high fermentative and
      hydrogenotrophic activities (80% and 95%, respectively).

PMID- 11575083
TI  - Degradation of lineal alkylbenzene sulphonate (LAS) in an acidogenic reactor
      bioaugmented with a Pseudomonas aeruginosa (M113) strain.
AB  - The degradation of of lineal alkylbenzene sulphonate (LAS) was studied in a two
      stage anaerobic system where the acidogenic reactor was bioaugmented with a
      strain of Pseudomonas aeruginosa (M113). This is a strain, which under aerobic
      and denitrifying conditions uses LAS as carbon source. Results show that LAS was
      only degraded within the acidogenic stage while in the methanogenic reactor there
      was no degradation and eventually there was an inhibition due to a LAS
      accumulation in the sludge. During the experiment, the M113 strain remained in
      the acidogenic conglomerate (at around 10(4) CFU/mL) although there is no
      evidence of their involvement in LAS degradation.

PMID- 11575084
TI  - Anaerobic treatment for C and S removal in "zero-discharge" paper mills: effects
      of process design on S removal efficiencies.
AB  - Stringent environmental laws in Europe and Northern America lead to the
      development towards closure of the process water streams in pulp and paper mills.
      Application of a "zero-discharge" process is already a feasible option for the
      board and packaging paper industry, provided in-line treatment is applied.
      Concomitant energy conservation inside the mill results in process water
      temperatures of 50-60 degrees C. Thermophilic anaerobic treatment complemented
      with appropriate post-treatment is considered as the most cost-effective solution
      to meet re-use criteria of the process water and to keep its temperature. In the
      proposed closed-cycle, the anaerobic treatment step removes the largest fraction
      of the biodegradable COD and eliminates "S" as H2S from the process stream,
      without the use of additional chemicals. The anaerobic step is regarded as the
      only possible location to bleed "S" from the process water cycle. In laboratory
      experiments, the effect of upward liquid velocity (Vupw) and the specific gas
      loading rate (Vgas) on the S removal capacity of thermophilic anaerobic bio
      reactors was investigated. Acidifying, sulphate reducing sludge bed reactors were
      fed with partly acidified synthetic paper mill wastewater and were operated at 55
      degrees C and pH 6. The reactors were operated at organic loading rates up to 50
      g COD.l-1.day-1 at COD/SO4(2-) ratios of 10. The effect of Vupw was researched by
      comparing the performance of a UASB reactor operated at 1.0 m.h-1 and an EGSB
      reactor, operated at 6.8 m.h-1. The Vupw had a strong effect on the fermentation
      patterns. In the UASB reactor, acidification yielded H2, acetate and propionate,
      leading to an accumulation of reducing equivalents. These were partly disposed of
      by the production of n-butyrate and n-valerate from propionate. In the EGSB
      reactor net acetate consumption was observed as well as high volumetric gas (CO2
      and CH4) production rates. The higher gas production rates in the EGSB reactor
      resulted in higher S-stripping efficiencies. The effect of Vgas was further
      researched by comparing 2 UASB reactors which were sparged with N2 gas at a
      specific gas loading rate of 30 m3.m-2.day-1. In contrast to the regular UASB
      reactors, the gas-supplied UASB showed a more stable performance when the organic
      loading rates were increased. Also, the H2S stripping efficiency was 3-4 times
      higher in the gas-supplied UASB, reaching values of 67%. Higher values were not
      obtained owing to the relatively poor sulphate reduction efficiencies.

PMID- 11575085
TI  - Influence of porosity and composition of supports on the methanogenic biofilm
      characteristics developed in a fixed bed anaerobic reactor.
AB  - This paper reports on the influence of the material porosity on the anaerobic
      biomass adhesion on four different inert matrices: polyurethane foam, PVC,
      refractory brick and special ceramic. The biofilm development was performed in a
      fixed-bed anaerobic reactor containing all the support materials and fed with a
      synthetic wastewater containing protein, lipids and carbohydrates. The data
      obtained from microscopic analysis and kinetic assays indicated that the material
      porosity has a crucial importance in the retention of the anaerobic biomass. The
      polyurethane foam particles and the special ceramic were found to present better
      retentive properties than the PVC and the refractory brick. The large specific
      surface area, directly related to material porosity, is fundamental to provide a
      large amount of attached biomass. However, different supports can provide
      specific conditions for the adherence of distinct microorganism types. The
      microbiological exams revealed a distinction in the support colonization. A
      predominance of methanogenic archaeas resembling Methanosaeta was observed both
      in the refractory brick and the special ceramic. Methanosarcina-like
      microorganisms were predominant in the PVC and the polyurethane foam matrices.

PMID- 11575086
TI  - Flotation technique with coagulant and polymer application applied to the post
      treatment of effluents from anaerobic reactor treating sewage.
AB  - This paper presents the results of a study performed with a lab-scale batch DAF
      unit fed with previously coagulated (with FeCl3 and/or cationic polymer) effluent
      from a pilot-scale expanded bed anaerobic reactor treating domestic sewage. The
      association between ferric chloride and polymers was studied, aimed at sludge
      reduction. Ferric chloride dosages ranging from 15 to 65 mg.l-1, and polymer
      dosages from 0.25 to 7.0 mg.l-1 were investigated. Flocculation conditions were
      kept constant: 20 min of time (Tf) and 80 s-1 of mean velocity gradient (Gf). Air
      requirement was kept to 19.0 g of air.m-3 wastewater, using 20% recycle ratio and
      saturation pressure at 450 kPa. When the anaerobic reactor was operating at
      steady state conditions, it was possible to reduce the FeCl3 dosage from 65 to 30
      mg.l-1 after applying 0.4 mg.l-1 of non-ionic polymer, before the DAF process.
      For these dosages, 79% COD removal (residual of 23 mg.l-1), 86% total phosphate
      removal (residual of 0.9 mg.l-1) and 98% turbidity removal (residual of 2.6 NTU)
      were observed. Furthermore, the use of adequate polymer together with 30
      mgFeCl3.l-1 leads to the production of high rising rate flocs.

PMID- 11575087
TI  - Post-treatment of anaerobic effluents in constructed wetland systems.
AB  - This papers describes the behaviour of wetlands as a post-treatment unit for
      anaerobically treated sewage for the removal of organic matter, suspended solids,
      nutrients (nitrogen and phosphorus) and faecal coliforms. Raw sewage was treated
      in a UASB reactor with a retention time of 5 h and the effluent was used in four
      units of wetlands with coarse sand as the medium and operated with different
      hydraulic loads. Three of the units had emerging macrophytes (Juncus sp), whereas
      the fourth one was operated as a control unit without plants. During the 12
      months of operation, the organic material removal efficiency (measured as COD)
      was in the range of 79 to 85%, whereas suspended solids removal varied from 48 to
      71%. Faecal coliform removal was very high (99.99%); phosphorus was also
      efficiently removed (average efficiency of 90% for the lowest hydraulic load),
      but nitrogen removal was only partial (45 to 70% for ammonia and 47 to 70% for
      TKN). The experimental results clearly show the technical feasibility of using
      wetlands for treatment of municipal sewage after a pre-treatment in the UASB
      reactor.

PMID- 11575088
TI  - Feasibility of a pilot-scale UASB/trickling filter system for domestic sewage
      treatment.
AB  - This paper presents the results of pilot system comprised of one UASB reactor
      followed by one trickling filter (TF). The UASB reactor had a volume of 416
      litres, being operated at an average hydraulic retention time (HRT) of 4 hours.
      The trickling filter had a useful volume of 60 litres, being operated at
      hydraulic and organic loading rates varying from 3.4 to 30.6 m3/m2.d and 0.3 to
      3.9 kg BOD/m3.d, respectively. These different operational conditions
      characterised eight research phases. Both reactors were fed with domestic sewage
      pumped directly from the main interceptor of Belo Horizonte City, Brazil. After
      almost 16 months of continuous monitoring, the UASB/TF system produced very good
      results in terms of COD and BOD removal, and also very low solids concentration
      in the final effluent. The average results of COD and BOD removal varied from 74
      to 88% and from 80 to 94%, respectively, sufficient to maintain the COD
      concentration in the final effluent in the range of 60 to 120 mg/L and the BOD
      values systematically below 60 mg/L. The overall averages of SS in the final
      effluent were kept below 30 mg/L. The UASB/TF system is a very promising
      alternative for the treatment of domestic sewage in Brazil and other developing
      countries, since the system can be designed with very short hydraulic retention
      times, resulting in a very compact and low cost treatment unit. Besides, the
      energy consumption and the labour costs are minimal.

PMID- 11575089
TI  - Polishing ponds for post-treatment of digested sewage. Part 1: Flow-through
      ponds.
AB  - Polishing ponds are used to improve the quality of effluents from efficient
      anaerobic sewage treatment plants like UASB reactors, so that the final effluent
      quality becomes compatible with legal or desired standards. The residual organic
      material and suspended solids concentrations in the digested sewage are reduced,
      but often the main objective of polishing ponds is to improve the hygienic
      quality, measured by the concentration of two indicator organisms: helminth eggs
      and faecal coliforms (FC). The FC removal is normally the slowest process and for
      that reason becomes the main design criterion for a polishing pond. By contrast
      in conventional waste stabilisation pond (WSP) systems the organic material
      removal is the governing design parameter. The feasibility of operating a single
      polishing pond for the post-treatment of UASB effluent is shown in this paper and
      the final effluent quality as a function of the retention time is discussed. Even
      under the most adverse weather conditions (several weeks of rain) the population
      of algae remained stable and produced enough oxygen to maintain a predominantly
      aerobic environment. The final effluent TSS and BOD concentrations were not very
      low for retention times of less than 1 week, but this could be attributed to the
      presence of algae in the final effluent. Filtered effluent BOD and TSS
      concentrations were very low. For retention times of more than 1 week algae were
      efficiently removed from the liquid phase by the action of predators and algae
      flocculation and settling, so that a final effluent with a very low BOD and TSS
      concentrations was produced. To maximise the FC removal efficiency the polishing
      pond was constructed with the objective of approaching a plug flow regime.
      However, the observed efficiency was well below the expected value for all
      retention times, which was attributable to imperfections of the flow regime. From
      tracer studies it was established that the dispersion number was in the range of
      0.14 to 0.16, which means that moderate mixing occurred, even though the pond was
      designed to avoid mixing as much as possible. Also the dead volume fraction
      ranging from 0.12 to 0.15 was quite considerable. Due to these imperfections the
      required retention time for an effluent to be used in unrestricted irrigation was
      produced for a retention time of about 10 days, twice the value of the minimum
      retention time for a batch or true plug flow pond. Although the plug flow regime
      could not be approached in practice, the required retention time of 10 days is
      still very much shorter than the value used in conventional WSPs (20 to 30 days).

PMID- 11575090
TI  - Domestic sewage treatment in a pilot system composed of UASB and SBR reactors.
AB  - The results obtained from the operation of a treatment system composed of an
      anaerobic (up-flow sludge blanket-UASB) reactor followed by an aerobic
      (sequencing batch-SBR) reactor treating domestic sewage are presented and
      discussed. The pilot plant was monitored during 6 months, aiming to obtain
      performance data on organic matter, nitrogen and phosphate removal under
      different operating conditions. The UASB reactor was operated at a constant
      hydraulic detention time (0) of 6 h while the SBR performance was monitored in
      four different duration cycles (24, 12, 6 and 4 h) corresponding to aeration
      times (AT) of 22, 10, 4 and 2 h, respectively. COD and TSS overall removal
      efficiencies (Eo) up to 91% and 84%, respectively, were achieved independently on
      the aeration time applied to the SBR. In respect to nitrification and phosphate
      removal, AT was found to be a determining operating parameter. TKN removal of
      approximately 90% was achieved for AT equal to or higher than 10 h; complete
      nitrification occurred for AT higher than 4 h; significant phosphate removal
      (72%) occurred only at the AT of 2 h. It was not possible to achieve simultaneous
      efficient removal of nitrogen and phosphate, under the operating conditions
      imposed on the treatment system.

PMID- 11575091
TI  - Combined anaerobic/aerobic (UASB + UBAF) system for organic matter and nitrogen
      removal from a high strength industrial wastewater.
AB  - The paper presents the experimental results collected from seven months of
      operation of a combined anaerobic/aerobic system treating an industrial effluent
      with averaged content of organic matter and nitrogen of 10.4 g COD/L and 790 mg
      NKT/L, respectively. The system was formed by an upflow anaerobic sludge blanket
      (UASB) and an upflow biological aerated filter (UBAF) connected in series, with a
      recycling line of the UBAF effluent into the UASB for its denitrification. The
      best results were obtained when operating the two reactors, UASB and UBAF, with
      hydraulic retention times (HRT) of 3.3 and 1.3 days, respectively, and a
      recycling ratio of 6.7. Under these conditions the system removed 98% of the
      organic matter and ammonia and 91% of the total nitrogen entering the system. The
      activity of the different microorganisms was followed through activity assays
      consisting of measuring the consumption or production rate of any specific
      substrate or metabolism product. Thus when operating the system under the
      aforementioned conditions the reported values for the specific activity of
      methanogenic microorganisms and denitrifiers coexisting in the UASB were 1.05 g
      COD/g VS d and 32.08 mg NO3-N/g VS d, respectively. While the activity of ammonia
      and nitrite oxidizers within the UBAF were 47.65 and 4.36 mg O2/g VS h,
      respectively.

PMID- 11575092
TI  - Removal of organic carbon, nitrogen and phosphorus in sequential batch reactors
      integrating the aerobic/anaerobic processes.
AB  - The performance of a bench-scale apparatus composed of two sequential batch
      reactors (SBR), forming an anaerobic/aerobic treatment system, was evaluated as
      to its potential use for biological removal of organic matter and nutrients. Both
      the reactors with 12.5 L of useful volume each were operated for the batch cycles
      of 12 hours receiving 8.0 L of substrate in each cycle. The first reactor (SBRAn)
      fed with synthetic substrate simulating domestic sewage was meant to remove the
      largest fraction of carbonic matter and to promote the substrate ammonification.
      The second reactor (SBRAe) was operated under alternating aerobic and anoxic
      conditions to establish conditions for achieving nitrification; denitrification
      and biological phosphate removal in the same batch cycle. Sodium acetate was used
      as an external carbon source for phosphate removal. Processes monitoring included
      the analyses of: COD, NTK-N, NH4(+)-N, NO2(-)-N, NO3(-)-N, PO4(3-)-P, alkalinity,
      volatile acids, pH, redox potential total, fixed and volatile solids. Under the
      operating conditions imposed, the system exhibited high performance in removing
      organic matter (COD), nitrogen and phosphorus, producing effluent with COD, NTK-N
      and PO4(3-)-P concentrations lower than 50.0 mg/L, 4.0 mg/L and 1.0 mg/L,
      respectively.

PMID- 11575093
TI  - Evaluation of an anaerobic/aerobic system for carbon and nitrogen removal in
      slaughterhouse wastewater.
AB  - In this work the performance of an anaerobic UASB reactor coupled with an
      activated sludge reactor for carbon and nitrogen removal in slaughterhouse
      wastewater is investigated. Periods with and without recirculation of aerobic
      effluent over 165 days are analysed. Working with a recirculation ratio of 2,
      removal efficiencies up to 90% and 65% are obtained for DQO and total nitrogen
      (TN), respectively. Higher recirculation ratios caused severe washout of active
      biomass in both reactors due to the high hydraulic loading rates applied.
      Denitrification in the UASB reactor was complete, with no nitrite accumulation
      and mainly to nitrogen gas. Significant decreases in COD removal efficiencies in
      the UASB reactor were observed at recirculation ratio of 2. Sudden decreases in
      total nitrogen efficiencies were related to inhibition process of nitrifying
      microorganisms, especially at high recirculation ratios.

PMID- 11575094
TI  - Nitrification-denitrification of UASB effluents highly loaded with nitrogen in an
      activated sludge reactor operated with short cycled aeration.
AB  - A conventional activated sludge reactor operated with short cycled aeration was
      used for total nitrogen removal of UASB anaerobic reactor effluent containing
      nitrogen (up to 1,200 mg NKT/L) and organic matter (up to 2,000 mg COD/L).
      Initially the reactor was fed with synthetic water to progressively introduce the
      UASB effluent. This favored the acclimation of the microorganisms to the real
      environment. The results obtained throughout this study showed that initially the
      tested technology is feasible and can report significant cuts on operation and
      maintenance when compared to conventional activated sludge processes. Total
      nitrogen removal up to 66% was attained treating the effluent of an UASB process
      designed for treating the wastewater of a potato starch factory. Total nitrogen
      removal capacities ranging between 0.1 and 0.58 kg of nitrogen per cubic metre
      per day are reported. Short-cycled aeration allowed for a more efficient use of
      the oxygen supply for nitrification and the organic carbon content present in the
      wastewater for denitrification. This operating protocol has demonstrated serious
      advantages in terms of operation costs and simplicity when total nitrogen removal
      is wanted. Most of the existing activated sludge processes, i.e. single
      continuous flow reactors, can be updated for total nitrogen removal essentially
      at no cost, the inversion (aeration control system) is rapidly returned as
      reduction in energy expenditure.

PMID- 11575095
TI  - Methanogenic activity measurements by the MAIA biosensor: instructions guide.
AB  - The MAIA (Methanogenic Activity and Inhibition Analyser) is a titration (pH-stat)
      biosensor designed to determine the activity and inhibition related to
      acetoclastic methanogens. The main operational problems encountered in using this
      instrument are described.

PMID- 11575096
TI  - Application of an innovative methodology to improve the starting-up of UASB
      reactors treating domestic sewage.
AB  - This study shows the results obtained during the starting-up evaluation of an
      UASB reactor treating domestic sewage. It is located in the municipality of
      Ginebra, Valle del Cauca region in Colombia. Its design flow is 7.5 l/s with a
      maximum capacity of 10 l/s. The reactor was seeded with a deficient quality
      inoculum which accounted for 20% of the total reactor volume. The starting-up
      methodology comprised the sequential washing of the sludge (inoculum) by applying
      three different upflow velocities. This procedure resembles what other authors
      term the "selective pressure method". Once the sludge was washed, the reactor was
      started-up with an initial hydraulic retention time (HRT) of 24.9 hours, which
      was steadily reduced down to 6.7 hours in the final stage. Along the starting-up
      phase, there was a positive evolution in terms of quantity, quality and spatial
      distribution of the sludge. Consequently, there was a positive evolution in
      organic matter removal mechanisms. For HRT above 14 hours, the removal mechanisms
      were mainly physical whilst for HRT below 9 hours the removal mechanisms were
      mostly biological. Based on the above considerations and on the water quality
      parameters measured, it may be concluded that the start-up of an UASB reactor for
      domestic sewage treatment seeded with a low quality inoculum can be done with HRT
      as low as 15 or 12 hours. In this way, it is possible to reduce the starting-up
      period of these reactors down to 4 to 6 weeks, provided that the starting-up
      methodology is properly applied.

PMID- 11575097
TI  - Influence of agitation rate on the performance of a stirred anaerobic sequencing
      batch reactor containing immobilized biomass.
AB  - The present work reports on the influence of the mechanical agitation rates on
      the performance of a stirred anaerobic sequencing batch reactor containing
      immobilized biomass on polyurethane foam, as inert support, treating synthetic
      domestic wastewater. The reactor was operated at 30 degrees C and an 8-hour cycle
      was used to treat approximately 0.5 L of the synthetic substrate with a COD
      concentration of nearly 500 mg/L. The studied agitation rates ranged from no
      agitation to 750 rpm. The system attained non-filtered substrate removal
      efficiency greater than 83% when agitation was employed. A very short start-up
      period and good solid retention could be observed. The use of agitation increased
      the efficiency of the reactor and enabled reduction of the total cycle time. An
      empirical equation and a first-order kinetic model are proposed to analyze the
      influence of agitation rates on the reactor's performance.

PMID- 11575098
TI  - Anaerobic treatment of domestic sewage at low temperature.
AB  - The results of research concerning the feasibility of anaerobic treatment of
      domestic sewage at low temperature are summarized in this article. The batch
      tests demonstrated a high biodegradability of domestic sewage at 20 degrees C
      (74%). Both batch and continuous experiments for the treatment of domestic sewage
      showed that the removal of SS prior to anaerobic treatment of domestic sewage not
      only provides a stable reactor performance but also improves the removal of both
      colloidal (CODcol) and dissolved COD (CODdis). The results of the pre-treatment
      of domestic sewage in an anaerobic filter (AF) and an anaerobic hybrid (AH)
      reactor showed that the AF reactor is an efficient process for the removal of
      suspended COD (CODss), viz. 82%, at an HRT of 4 h and 13 degrees C. The novel AF
      reactor consists of vertical sheets of reticulated polyurethane foam with knobs,
      where the biomass was only in attached form. For the treatment of pre-settled
      sewage at 13 degrees C, the AH reactor, with granular sludge, showed a higher
      total COD (CODt) removal than the UASB reactor as a result of higher CODcol
      removal. Therefore, the performance of a two-step system, AF + AH (with granular
      sludge) reactor, was investigated with different HRTs at 13 degrees C. For
      optimization of CODss and CODdis an HRT of 4 + 4 h is needed, while for
      optimization of CODcol removal an HRT of 4 + 8 h is required. A CODt removal of
      71% was achieved with 60% conversion to methane from the removed CODt when the AF
      + AH system was operated at an HRT of 4 + 8 h at 13 degrees C.

PMID- 11575099
TI  - An integrated anaerobic--physico-chemical treatment concept for wool scouring
      wastewater.
AB  - The strong flow wastewater from a wool scouring industry is treated by a
      combination of anaerobic digestion and physico-chemical postreatment. Based on
      previous laboratory results (Gutierrez et al., 1999), three anaerobic baffled
      reactors (ABR) of 300 m3 each were built, processing 60% of the strong flow of a
      wool scouring mill for about two years. COD and grease removal in the anaerobic
      reactors were 47-50% and 50-55% respectively, with an organic load between 8.9
      and 6.7 kg COD/m3 d. The effluent of the anaerobic reactors was assayed with
      additives in an industrial decanter centrifuge. As results of these assays, all
      the effluent of the three reactors was sent to the decanter centrifuge after
      dosing additives. Overall COD and grease removal of the integrated system were
      87% and 93% respectively. Dosage of coagulation-flocculation additives was
      optimized in a continuous flocculation device. The proposed treatment is cheaper
      and easier to control than others alternatives with COD removal higher than 93%.

PMID- 11575100
TI  - Effects of organic, hydraulic and fat shocks on the performance of UASB reactors
      with intermittent operation.
AB  - Three lab-scale UASB reactors operated at 35 degrees C in an intermittent mode
      were subject to different step shocks: hydraulic, organic and feed fat content.
      The results show that the reactors have good resistance to the applied shocks and
      suggest that a feedless period is beneficial to the performance of the reactors,
      due to stabilisation of accumulated organic matter.

PMID- 11575101
TI  - Blanket development in a malting wastewater anerobic treatment.
AB  - A 3 m3 pilot UASB reactor was operated with malting wastewater. In order to find
      the aggregation characteristics, the sludge concentration profile was determined
      throughout time. Reactor behaviour concerning the physical properties of the
      sludge can be evaluated using this procedure. Moreover, organic load per VSS can
      be calculated from this profile. The organic load based per VSS is more accurate
      as a design parameter than the volumetric load. Under the study conditions
      imposed the COD removal efficiencies achieved were about 85%. Organic loads of
      0.6-0.7 kg COD/(kgVSS.d) were reached. After operating at 30 degrees C,
      temperatures of 28 degrees C and 15 degrees C were tested, showing no decrease in
      COD removal efficiency. At week 15 the presence of granules was verified, and
      after that, sludge concentrations of 30-35 kg VSS/m3 were measured at the bottom
      of the reactor. The SVI of the granular sludge decreased to values below 20
      mL/gVSS. The settlement velocity was 10 m/h, which is much greater than the
      recommended values for the settlement zone; therefore, no problems are to be
      expected in the settler regarding the sludge sedimentation. The biomass yield
      coefficient obtained was 0.10 gVSS/gCOD in agreement with literature values for
      brewering effluent.

PMID- 11575102
TI  - Bamboo as an anaerobic medium: effect of filter column height.
AB  - Sewage was treated in anaerobic filters filled with rings of bamboo (either whole
      or cut), and their effectiveness in the reduction of chemical oxygen demand (COD)
      was monitored along the entire extension of the filter. This efficiency was
      determined based on the COD reduction in both the brute effluent (COD-T) and that
      passed through a glass filter (COD-F). The quantity of total suspended solids
      (TSS) present at various heights in the filter column, measured at approximately
      10-cm intervals from the false bottom to the height of the filter outflow (80 cm
      above) for various hydraulic detention times (HDT). The performance of the system
      resulted in little variation up to 5 hours of HDT, with the percentage of
      reduction of COD-T and COD-F being situated in the range of 60-80% and 40-80%,
      respectively. The first 40 cm of the filter proved to be relatively effective,
      and no significant differences in performance between whole and cut rings of
      bamboo were observed. A shock in pH occurring after 562 days of operation
      provoked an immediate and marked decrease in the performance of the reactors,
      especially that operating with a HDT of only 2 hours. This latter filter required
      more time to return to normal operational conditions than did the other reactors
      operating with longer HDT.

PMID- 11575103
TI  - Influence of HRT (hydraulic retention time) and SRT (solid retention time) on the
      hydrolytic pre-treatment of urban wastewater.
AB  - This work presents the results obtained from a study on the pretreatment of urban
      wastewater using a digester that acted as a system for the retention of solids
      (sedimentation-filtration), hydrolysis of the retained solids and acidification
      of the dissolved substances. After start-up (Phase I), the digester was operated
      at hydraulic retention times (HRT) of 4.4, 3.4 and 2.2 h and at solid retention
      times (SRT) of 24, 16 and 14 d, during Phases II, III and IV, respectively. The
      retention and removal of suspended solids (SS) was maintained slightly above 60%,
      independently of HRT and SRT. Conversely, eliminated chemical oxygen demand (COD)
      decreased slightly upon reducing HRT and SRT. The influence of these two
      parameters on the generation of volatile fatty acids (VFA) is more notable,
      reaching effluent VFA concentration of 29 (Phase II), 96 (Phase III), and 107
      (Phase IV) mg COD/I. VFA to SS generation ratios were 0.13 (II), 0.35 (III), and
      0.48 (IV) g VFACOD/g SS added. Optimum values were reached at an HRT of 2.2 h.
      Taking 100 kg influent COD as a base, the conversion of different kinds of COD
      was as follows (in kg influent: kg effluent): VFACOD(4:17), non-VFA soluble COD
      (45:23), VSSCOD (51:23). Simultaneously to these conversions, 2 kg VSSCOD are
      generated as purge stream and 35 kg COD are eliminated during the process.

PMID- 11575104
TI  - Denitrification on the top of UASB reactors of rice wastewaters.
AB  - Parboiled rice industry is one of main food industries in the south of Brazil.
      The main parts of the processing are the humidification and gelatinization of the
      grain. This procedure increases the productivity and nutritive and cooking values
      of the product. Some of these industries in the region utilize upflow anaerobic
      sludge blanket (UASB) reactors as a biological treatment for carbon removal. For
      nitrogen removal, the proposed system aims to eliminate an extra denitrification
      reactor, making this step in the top of the UASB, an anoxic zone of the reactor.
      Nitrification was performed in aerated mixed reactor of 3.6 L.A fraction of the
      NR was recycled in the top of UASB reactor above the sludge blanket. Recycled
      ratio varied from 0; 1:0.5; 1:1.0; to 1:1.5. The maximum removal efficiency of
      NTK was 80%. The results confirm the viability of the proposed system for
      denitrification.

PMID- 11575105
TI  - The use of upflow anaerobic sludge blanket reactors in the treatment of poultry
      slaughterhouse wastewater.
AB  - This work studied the performance of the dissolved air flotation (DAF) system and
      the start-up and the operation of two 450 m3 UASB reactors in a poultry
      slaughterhouse in Sorocaba, Brazil. The DAF presented reduction efficiency of
      grease and fats, suspended solids and COD 50% higher. The reactors were seeded
      with non-adapted sludge. The average COD of the reactor influent was 2,695 mg/L;
      and the initial organic loading rate (OLR) and the initial sludge loading rate at
      the start-up were 0.51 kg COD/m3.day and 0.04 kg COD/kg VTS.day, respectively.
      The start-up period was 144 days. During this time the reactor flow rate and OLR
      were gradually increased. At the reactor start-up, the maximum OLR value was 2.1
      kg COD/m3.day, the COD reduction was higher than 80%, and the concentration of
      volatile fatty acids (VFA) was below 100 mg/L. The COD reductions, considering
      the reactor effluent raw COD and soluble COD were similar throughout the period
      studied in both reactors. The reactor effluent raw COD was approximately 10%
      higher than the soluble COD until the 225th day of operation. From the 225th day
      of operation this value increased 20%-30% due to the sludge washout. The effluent
      soluble COD reduction, the effluent VFA concentration and the operational
      stability attested the good performance of UASB reactors in poultry
      slaughterhouse wastewater treatment.

PMID- 11575106
TI  - Production and oxidation of methane at low temperature by the microbial
      population of municipal sludge checks situated in north-east Europe.
AB  - Methanogenic and methane-oxidizing activities of the microbial population of
      sewage sludge checks (Moscow and Syktyvkar regions) were studied at temperatures
      ranging from 5 to 25 degrees C. The number of methanogens in silt samples reached
      10(10) cells/ml. A temperature decrease from 25 to 5 degrees C led to a sharp
      decrease of methanogenesis in the silt samples. Nevertheless, methanogenesis was
      still significant even at 5 degrees C. Different organic substrates, including
      polymeric and aromatic compounds, were degraded with methane production at 6
      degrees C. At depths of 20-40 cm the number of methanotrophic bacteria reached
      10(11) cells/ml. Methane oxidative activity of the microbial populations in the
      silt was less sensitive to the 25 degrees to 5 degrees C temperature decrease.
      Ten methanotrophic species, able to grow at 6 degrees C, were enriched from the
      Syktyvkar sludge lagoon and identified by indirect immunofluorescence.
      Enrichments obtained from the Syktuvkar region (62 N) contained more species of
      methane oxidizing bacteria able to grow at low temperature then methanogenic
      enrichments obtained from Moscow region (56 N).

PMID- 11575107
TI  - Removal of fecal indicator organisms and parasites (fecal coliforms and helminth
      eggs) from municipal biologic sludge by anaerobic mesophilic and thermophilic
      digestion.
AB  - In this work, two egg-shaped, 5L-volume, anaerobic sludge digesters were used,
      one under mesophilic conditions (35 degrees C, M1), and the other under
      thermophilic conditions (55 degrees C, T1). Both digesters were fed with the
      purged sludge from an anaerobic treatment plant (start-up period) and from an
      activated sludge plant (stabilization period), treating municipal wastewaters.
      The purpose of the study was to establish the technical feasibility of the
      anaerobic thermophilic sludge treatment comparatively, during the stages of start
      up and stabilization of the process, for removing pathogenic microorganisms and
      parasites efficiently. The results show that, in both stages, the anaerobic
      thermophilic digester presents higher efficiency on the removal of pathogens and
      parasites, than the mesophilic digester. Anaerobic thermophilic digestion is
      close to complying with the EPA (1998) limits for "Class A" type biosolids,
      referring to the number of parasitic helminth eggs (0.25 HELarval/gTS), and to
      the pathogen indicator fecal coliforms (< 1000 MPN/gTS). Therefore, the results
      show that thermophilic anaerobic digestion of biologic sludge may be considered
      as a suitable technology for the production of Class A biosolids, for further use
      in agriculture without restrictions.

PMID- 11575108
TI  - Long-term follow-up of peripheral ossifying fibroma: report of three cases.
AB  - Peripheral ossifying fibroma is a non-neoplastic enlargement of the gingiva that
      is classified as a reactive hyperplastic inflammatory lesion. It is possible to
      misdiagnose peripheral ossifying fibroma as pyogenic granuloma, peripheral giant
      cell granuloma, or odontogenic tumors. Therefore, histopathological examination
      is essential for an accurate diagnosis of such lesions. Differential diagnosis is
      important, because peripheral ossifying fibroma has a tendency to recur. This
      article describes three cases of peripheral ossifying fibroma, which were
      followed for 4 years without any sign of recurrence. By presenting these cases,
      we emphasize the importance of proper excision and aggressive curettage of the
      adjacent tissues for prevention of recurrence.

PMID- 11575109
TI  - Blood flow of free gingival grafts measured by xenon-133 clearance.
AB  - Blood circulation of free gingival grafts by Xe-133 clearance was evaluated in
      this study with special attention to the relationship between the amount of
      circulation and graft thickness, surface area and contraction during the initial
      healing phase. Following baseline clinical examination and initial periodontal
      therapy, 32 patients received mucogingival surgery with free gingival grafts for
      treatment of insufficient attached gingiva. Blood flow in recipient and donor
      areas was measured by injection of Xe-133. Xenon clearance in the free gingival
      grafts was measured at the first, tenth, twentieth, and fortieth days. Mean blood
      flow was observed to decrease on the first day and then gradually increased at 10
      and 20 days and finally reached the initial value of the recipient area on the
      fortieth day. It was observed that circulation in the grafted tissue was
      positively correlated with graft thickness, but negatively correlated with graft
      contraction during healing.

PMID- 11575110
TI  - Clinical significance of antibiotic therapy in guided tissue regeneration with a
      resorbable membrane.
AB  - This study was designed to evaluate the clinical significance of antibiotic
      therapy combined with guided tissue regeneration (GTR) therapy with a collagen
      membrane. The subjects were 20 adults diagnosed with periodontitis (20 intrabony
      periodontal defects). Ten patients were treated with GTR alone (control group)
      and the other 10 patients were treated with a combination of GTR and antibiotics
      (antibiotic group). In the antibiotic group, minocycline ointment was applied
      locally before GTR therapy, and doxycycline and amoxyline were systemically
      administered after GTR therapy. Clinical manifestations, the presence or absence
      of exposed membrane, and microbiological findings were assessed 1 month before,
      immediately after, and 2 weeks, 6 weeks, and 3 months after GTR therapy. The
      results showed no significant differences in reduction of probing depth, probing
      attachment gain (PAG), or the ratio of PAG to intraoperative depth of the
      intrabony defect (vertical relative attachment gain) between the antibiotic group
      and the control group before and 3 months after GTR therapy. A DNA probe test and
      specific enzymatic activity test revealed no significant differences in the
      improvement and the rate of bacterial negativity before, and 6 weeks and 3 months
      after, GTR therapy. These findings indicate that antibiotic therapy is not
      clinically beneficial when combined with GTR therapy with a collagen membrane.

PMID- 11575112
TI  - Periodontal and alveolar bone abnormalities associated with
      pachydermoperiostosis.
AB  - Pachydermoperiostosis (PDP) is an unusual syndrome manifested clinically by
      finger clubbing, extremity enlargement, hypertrophic skin changes, and periosteal
      bone formation. A rare case of pachydermoperiostosis (primary hypertrophic
      osteoarthropathy) with oral manifestations in a 47-year-old man is presented. The
      possible correlation between physiological mechanisms of this disease and their
      influence on oral periodontal tissues and alveolar bone is discussed.

PMID- 11575111
TI  - Epithelioid hemangioendothelioma of the maxilla: case report and review of
      literature.
AB  - Epithelioid Hemangioendothelioma (EH) is a rare, low-grade malignant vascular
      tumor, first defined as a soft tissue tumor by Enzinger and Weiss in 1982. The
      tumor was later reported in virtually all sites, including liver, lung, brain,
      and bone. The epithelioid neoplastic cells are of endothelial origin, staining
      positive for Factor VIII and CD-34. In our review of EH of bone medline
      literature, and including the present case report, a total of 73 cases were
      found. Forty-one (56%) patients had multifocal bone involvement and thirty-two
      (44%) patients had solitary EH of bone. Resection was the primary recommended
      treatment. Visceral involvement appears to affect prognosis and survival
      adversely. We report a case of EH of the maxilla, which occurred in a 32-year-old
      male.

PMID- 11575113
TI  - ART--what for?

PMID- 11575114
TI  - Evaluation of Atraumatic Restorative Treatment restorations and sealants under
      field conditions.
AB  - Conventional restorative procedures require the use of dental materials,
      expensive equipment, instruments and electricity. This makes dental restorations
      costly and limits the availability and accessibility of the service to areas
      where these facilities are available. The new philosophy of restorative care
      requires minimal intervention and advocates early interception of the caries
      process through the use of glass-ionomers as sealants and as restorations. This
      new approach makes dental care accessible to all members of society in developing
      countries. The aim of this study was to evaluate the use of Atraumatic
      Restorative Treatment (ART) restorations and sealants under field conditions.
      Both were assessed for their retentive properties and the development of
      secondary caries adjacent to the procedures. A longitudinal study design was
      followed. ART restorations and sealants were assessed at intervals of 6 and 12
      months. After 12 months 56.5% of ART restorations were still present in the
      primary dentition and 84% in the permanent dentition. Of these 85.1% had no
      defects in the primary and 78.6% no defects in the permanent teeth. 72.3% of
      primary and 92% of permanent teeth on which ART restorations were placed had no
      caries after 1 year. Even though most of the sealants were absent due to poor
      retention after 12 months (89.6%), 98.9% of the teeth where the sealant was
      initially placed had no caries. Only 6.3% of sealants present had marginal
      defects. The ART technique is strongly recommended for the management of small,
      occlusal carious lesions in primary and permanent teeth.

PMID- 11575115
TI  - Surface roughness of aesthetic restorative materials: an in vitro comparison.
AB  - The purpose of this study was to compare the surface roughness of three types of
      aesthetic restorative material. Six standard samples of two brands of each type
      of material were prepared namely: hybrid composites (Prodigy, Z100), compomers
      (Compoglass F, Hytac Aplitip) and glass ionomer cements (Photac-Fil, Vitremer) in
      a perspex mould (N = 36). Upper and lower surfaces were covered with Mylar strips
      which, in turn, were covered with glass slides and compressed to express excess
      material. After light curing, specimens were stored in distilled water for 14
      days. Thereafter, one side of each specimen was polished sequentially with
      medium, fine and super fine Soflex discs (treatment). Untreated surfaces served
      as controls. All surfaces were examined with Talysurf and the surface roughness
      (Ra) of each specimen was recorded. Three measurements were made of each
      specimen. A 4-way ANOVA and Tukey's Studentised range test were used to analyse
      the data. Statistically significant effects were found for both type of material
      (P = 0.0001) and for treatment process (P = 0.0065). Among unpolished specimens:
      Compoglass F is significantly rougher than Vitremer, Z100, Prodigy and Hytac
      Aplitip, and compomers are significantly rougher than hybrids. Among polished
      specimens: Photac-Fil is significantly rougher than Z100 but does not differ from
      Compoglass F, Vitremer, Prodigy and Hytac Aplitip, and glass ionomers are also
      significantly rougher than hybrids. The smoothest surface is obtained when curing
      materials against a Mylar strip.

PMID- 11575117
TI  - Implementation of the ART approach in South Africa: an activity report.
AB  - The Atraumatic Restorative Treatment (ART) approach has been adopted in public
      dental services in South Africa as an appropriate and economical means to provide
      basic restorative care in communities where it was not possible before. The
      approach also offers a less-traumatic treatment concept for fearful patients and
      children in the private dental practice. In 2000, the Division of Community
      Dentistry, University of the Witwatersrand, implemented a training, research and
      service programme in the ART approach. The aim of these activities was the
      promotion of ART at various levels within the oral health care system in the
      Republic of South Africa. The objectives of the programme were to initiate and
      provide training of oral health workers in ART, to evaluate the outcome of
      training and service programmes and to disseminate results. This paper describes
      the Division's ART activities in 2000, regarding public, private and refugee
      health services.

PMID- 11575118
TI  - Dental information systems (Pty) Ltd and managed dental care.

PMID- 11575119
TI  - [Mathematical model of the heat exchange between blood of large arteries and
      veins].

PMID- 11575120
TI  - [Oxygen consumption in the rat heart during superdeep hyperthermia].

PMID- 11575121
TI  - [Correlation of spatial EEG synchronization with verbal-logical and visual
      spatial abilities in humans].
AB  - The EEG was recorded from five monopolar leads: a spontaneous one as well as the
      EEG during verbal-logical or visual-spatial tests, in humans. The subjects with
      prevailing visual-spatial abilities had a spontaneous EEG with a low
      intercorrelation between the hemispheres and a higher level of the EEG
      synchronisation in parietal-occipital areas as compared with the frontal those,
      whereas subjects with prevailing verbal abilities had an inverse correlation of
      the above EEG parameters. The parameters' interrelationships in subjects'
      spontaneous EEG seem to reflect an individual and specific character of cerebral
      neurodynamics suggesting a negative correlation between the verbal-logical and
      visual-spatial abilities in humans.

PMID- 11575122
TI  - [Rheological of blood and oxygen transport in long-term adaptation to muscular
      load].
AB  - The blood viscosity became reduced after a long-term muscular adaptation in dogs.
      The main adaptation mechanism is associated with an autoregulated haemodilution
      and improvement of the red blood cells' microrheology (deformities and
      aggregation). The findings suggest that reduction in the haemodilution and the
      blood oxygen capacity are accompanied by a heightened efficiency of the oxygen
      transport. A sufficient correlation exists between the blood fluidity parameters
      and the oxygen balance in the body. Value of the optimum haematocrit in oxygen
      transport, is discussed.

PMID- 11575123
TI  - [Contraction-relaxation dynamics and mechanical restitution in the developing
      myocardium of the chick embryo].
AB  - Parameters of the contraction-relaxation cycle and mechanical restitution (MR)
      were assessed in isolated ventricular preparations of 3- and 4-day chick embryos
      (EM) and posthatched (PH) chicks. Ryanodine reduced the relaxation rate in the EM
      but increased it in the PH chicks. It also suppressed a rest-induced potentiation
      and the MR in all the preparations. Low Na superfusion significantly suppressed
      the relaxation and decreased the rest potentiation in the myocardial preparations
      all ages. The findings substantiate existence of a sarcolemmal Ca pool which
      participates in regulation of twitch parameters and Ca outflux via the Na-Ca
      exchange.

PMID- 11575124
TI  - [Participation of the dopaminergic brain system in effects of glucocorticoid
      hormones].
AB  - Following the conditioning with dexamethasone, a dose-dependent place preference
      in non-preferred compartment was observed on the second test day in male Wistar
      rats. Amphetamine in subthreshold dose exerted no effect if administered alone
      and induced a place preference in an unbiased paradigm after pre-treatment with
      dexamethasone. Administration of D2-dopamine receptors' antagonist sulpiride 30
      min prior to dexamethasone conditioning completely blocked the acquisition of the
      place preference. The D1-dopamine receptors' antagonist SCH23390 exerted no
      effect on the place conditioning. The findings suggest that the D2-dopamine
      receptors take part in conditioned place preference with dexamethasone.

PMID- 11575125
TI  - [Effect of cross-fostering on catalepsy and the brain monoamine level in rat
      offspring prone to catalepsy and in the control strain].
AB  - Duration of cataleptic reactions in male rats of Wistar and GC strains depended
      both on the genotype and on the type of rearing: it was longer in the GC rats
      than in the Wistar ones. In the GC males reared by Wistar foster mothers this
      parameter was smaller than in the control GC but higher than in Wistar rats. The
      NA content was significantly lower in the GC cortex, hypothalamus and striatum,
      and the level of serotonin and 5-HIAA was lower in cortex of the GC as compared
      with Wistar rats. The cross-fostering affected monoamine content in some brain
      structures. On the whole, serotonin, DA and NA systems of the GC rats proved to
      be more susceptible to stress caused by cross-fostering than those of the Wistar
      rats. The cross-fostering diminished interstrain differences in the NA level in
      cortex, striatum, and hypothalamus.

PMID- 11575126
TI  - [Individual typological characteristics of hormonal responses in dogs during
      psychoemotional stress].
AB  - Effects of psycho-emotional stress on contents of steroid hormones in the blood
      were studied in dogs with different typological properties of the higher nervous
      activity. Under stress condition, a significant correlation between the cortisol
      and testosterone levels and the dogs' typological characteristics was found. The
      more obvious fluctuations in the hormones level occurred in animals with strong
      and excitable type of the nervous system as compared with dogs belonging to weak
      and inert type.

PMID- 11575127
TI  - [Effect of calcium ion level in blood on physiological functions in rat subjected
      to immersion hypothermia].
AB  - I.v. administration of disodium salt of the ethylenediamine tetra-acetic acid to
      continuously immersed white rats intensified the rats' amplitude and rate of the
      respiration movement. I.v. administration of calcium chloride to the cooled rats
      diminished by 11.3% the respiration movement amplitude and by 20.7%--the muscles
      electrical activity. The findings confirm important role of the calcium ions in
      infringement of physiological functions under conditions of hypothermia.

PMID- 11575128
TI  - [Effect of chronic stress in prepubertal period on sexual arousal in the male
      rats].
AB  - Effects of two models of chronic stress were studied in adult male rats with
      inherited stress-induced arterial hypertension (ISIAH) and in Wistar rats. Intact
      males of both rat strains demonstrated a similar behavioural and hormonal
      activation in sexual arousal. Prepubertal chronic stress decreased the female
      induced behavioural response and the effect depended on the character of stress
      and the animal genotype. No long-lasting effects of pre-pubertal stress on the
      plasma corticosterone level in males under sexual arousal were observed.

PMID- 11575129
TI  - [Activation of latent pacemakers in the guinea pig ureter].
AB  - Guinea pig's ureter rhythmogenic autonomous latent pacemaker was shown to
      generate a significantly higher-frequency rhythm than the pericystic pacemaker.
      The latent pacemakers of the ureter middle portion can be activated with a breach
      of electrical conductivity across the organ or with chemical agents
      (noradrenaline, histamine).

PMID- 11575130
TI  - [Irregular zonal distribution of actinin and tropomyosin in the rat kidney].
AB  - The cortical actinin contents was found to be higher in the inner medulla of the
      rat kidney. Tropomyosin was distributed differently: it is lower in the cortex
      than in outer or inner medulla. The processes controlled by these proteins seem
      to be important for the vasopressin renal effects, and the irregular distribution
      of these proteins reflects participation of different renal areas in facultative
      water reabsorption.

PMID- 11575131
TI  - [Effect of vasopressin on water permeability of epithelial cells in the kidney
      collecting duct during postnatal ontogenesis in rats].
AB  - Desmopressin caused a statistically significant increase in the water
      permeability of the outer medullary collecting ducts (OMCD) in 22-days old rats.
      Concentration of specific V2 receptors increased during postnatal period.
      Comparison of the V2 receptors concentration, mRNA contents, and changes of water
      permeability in response to desmopressin suggests that parts of transduction
      mechanism is situated deeper than the receptors, determines the physiological
      mechanism at the end of weaning period.

PMID- 11575132
TI  - [Mechanisms of glucose absorption at a high carbohydrate level in the rat small
      intestine in vivo].
AB  - At low maltose concentations, the rates of maltose hydrolysis and glucose
      absorption increased with increasing substrate concentration in the infusate. A
      significant fluid secretion occurred in the isolated intestinal loop perfused
      with hypertonic maltose solution, but water fluxes were close to zero in case of
      almost isotonic perfusion solutions. The findings suggest that the active
      transport remains a main mechanism of glucose absorption at super-high maltose
      concentration as well. The rates of maltose hydrolysis and released glucose
      absorption in the isolated intestinal loops perfused with super-high maltose
      concentration, enhance mainly due to an increase of effective digestive
      absorptive surface of the villi and, in part, to substrate diffusion across the
      intestinal epithelium rather than paracellular solvent drag.

PMID- 11575133
TI  - [Generalized and selective feedback inhibition of secretion of pancreatic
      enzymes].
AB  - Selective inhibition of secretion of proteinases, amylase and lipase by the
      pancreas, was revealed. The inhibition is directly dependent on the dose of
      intraluminal enzymes. The latter's increase transforms the selective inhibition
      into a generalised one. Possible mechanisms of selective and generalised feedback
      inhibition of the exocrine pancreatic secretion is discussed, the secretion
      playing an important role in urgent adaptation of the pancreatic enzymes
      secretion to the duodenal chyme properties.

PMID- 11575134
TI  - [Mother thyroid status and development of enzymes of initial and final phases of
      carbohydrate hydrolysis].
AB  - The daily treatment of a lactating mother with thyroxine 50 micrograms/100 g b.w.
      from the first to 21st day of lactation resulted in an increase of the thyroxine
      level in serum and earlier induction of alpha-glycosidases (pancreatic alpha
      amylase and enteral maltase, saccharase) and in the earlier repression of beta
      galactosidases (intestinal lactase) in rats. In contrast, sucklings fed by
      hypothyroid mothers showed a low level of thyroxine and a delayed induction of
      alpha-glucosidases but ameliorated the repression of lactase.

PMID- 11575135
TI  - [More power for patients: the patients' forum--a joint platform for the medical
      profession and patient self-help groups].
AB  - New ways of cooperation between doctors and representatives of patients are
      followed with the help of the patients' forum which was founded on the initiative
      of the German Medical Association. Members of the German Association 'Help for
      the Handicapped People', the 'Forum of the Chronic Ill and Handicapped People' of
      the 'Equal Charitable Organisation' (Paritatischer Wohlfahrtsverband), the
      'German Association of Self-Help Groups' as well as representatives of the
      committees and the management of the German Medical Association and the National
      Association of Statutory Health Insurance Physicians form the patients' forum.
      The major aim of this cooperation is to discuss the possibilities and the ways to
      improve the quality in health care. A direct participation of patients'
      representatives is for the moment planned in the evaluation of the quality of
      medical information for the lay public. In cooperation with the Agency for
      Quality in Medicine--a joint institution of the German Medical Association and
      the National Association of Statutory Health Insurance Physicians--the quality of
      information on health care that is published in the internet should be examined.
      The patients' information service which was developed by the Agency for Quality
      in Medicine and is found under www.patienten-information.de is the basis for this
      examination.

PMID- 11575136
TI  - [Analysis of German language consumer information brochures on screening for
      colorectal cancer].
AB  - A total of 17 consumer brochures that deal with the screening for colorectal
      cancer were analysed by two independently working researchers. The aim was to
      assess the quality of the information as a basis for evidence-based informed
      decision making using pre-defined evaluation criteria. No brochures fulfilled the
      necessary criteria. In most brochures there was a lack of transparency of the
      information process. No data was provided for estimating individual risks of
      colorectal cancer morbidity or mortality. With respect to the efficacy of
      screening no data was provided about relative or absolute risk reductions, number
      needed to screen, number needed to harm, predictive rates and false positive
      rates. In conclusion, presently available information brochures in Germany do not
      allow informed decision-making by consumers.

PMID- 11575137
TI  - [Temporomandibular disorders: quality assessment of patient information on the
      world wide web].
AB  - AIM: Assessing of the methodological and medical-scientific quality of the German
      information on temporomandibular disorders (TMDs) provided then the World Wide
      Web (WWW). METHODS: The investigation was carried out with selected search
      machines (subject and index catalogues) as well as health portals. The search
      strategy involved the option "simple search" and the keyword "Kiefergelenk"
      ("temporomandibular joint"). The methodological quality was assessed using the
      DISCERN instrument. To assess the medical-scientific quality, a brief
      questionnaire based on comparisons with the current state of the scientific
      literature on TMDs was used. RESULTS: Twenty-seven of the 47 identified websites
      are longer than half a printed page (1/2 p). The methodological quality of all
      websites ranges between "low" and "moderate"; it is higher for information > 1/2
      p. There is no clear relationship between methodological (DISCERN) and medical
      scientific quality. For example, only five of seven websites with acceptable
      medical-scientific quality reach a moderate methodological quality, whereas the
      remaining two of these publications have a low methodological quality.
      CONCLUSIONS: There is a discrepancy between quantity and quality of the available
      information on TMDs. In general, there is a lack of evidence-based high-quality
      information for patients seeking information related to TMDs in the WWW. The
      available data suggests that TMD patients are not constantly provided with
      information regarding to the latest developments in research. Therefore, measures
      to improve the quality of care of these patients are necessary.

PMID- 11575138
TI  - [Systematic literature search to make HTA (health technology assessment)
      reports].
AB  - Health technology assessment should describe the existing evidence of a medical
      technology independently and complete. Because of the enormous amount of
      scientific publications worldwide, systematic literature investigation is
      essential to identify all publications of relevance. Systematic investigation
      implies especially hierarchical and standardized modes. The most important
      resources to identify publications that already contain a synthesis of
      information are specialized databases covering secondary literature. A
      standardized search strategy consists of several steps: conception (incl.
      specification of methodological and content-related inclusion and exclusion
      criteria), selection of databases, preparation of a query, and carrying out the
      search, finally. The identified publications--this could be several hundreds up
      to some thousands--have to be assessed by applying the a priori defined criteria
      and a decision has to be made whether to include or exclude documents for the
      health technology assessment report.

PMID- 11575139
TI  - [Current approaches for the implementation of guidelines by means of information
      technologies].
AB  - Clinical practice guidelines (CPGs) play an increasingly important role in the
      harmonisation process of health care delivery and disease management. It is known
      that nationally or internationally produced guidelines that have no consistent
      implementation strategy, have limited impact in changing physicians' behaviour
      and patterns of care. The literature provides evidence for the effectiveness of
      computerisation of CPGs for increasing compliance and improving patient outcomes.
      The integration of knowledge-based functions for decision support or monitoring
      in clinical information systems is one effective way. Another approach relies on
      the original, mostly text-based, guidelines. By structuring these resources with
      the eXtensible Markup Language (XML) we are able to improve the availability of
      clinically relevant knowledge at the point of care. XML allows for in-context
      searching and the customized presentation of guideline content. We are confident
      that this new approach will improve the acceptance and the benefits of the
      increasing number of guidelines in medicine.

PMID- 11575140
TI  - [Guideline development for general medicine: the problem of dichotomized
      algorithm development].
AB  - Development of clinical guidelines in Germany is based on two divergent
      principles. One is the clinical position of individuality and clinical
      experience. The other is the strong adherence to the principles of evidence-based
      medicine and the scientific method, as demonstrated by the clear, algorithmic
      methodology of critical pathway development. We discuss the pros and cons of both
      concepts and try to find some sort of practical middle ground between the two
      extremes.

PMID- 11575141
TI  - [Description of Internet-based models for continuing medical education. First
      results and experiences with asthma patients].
AB  - The Pilot study "Quality Development through the Internet" by the Horten Center
      is an integral part of a concept on dissemination of medical knowledge. It offers
      participants the possibility to compare interactively their own and their peers'
      performance with their competence and with accepted guidelines within a web-based
      Audit-Cycle. The participants can discuss the evidence-based recommendations
      which are offered. In addition, changes in behavior and care can be documented
      objectively.

PMID- 11575142
TI  - [Proceedings of the French Society for the Study of Fertility meeting on the
      placenta. Montpellier, France, May 10, 2001].

PMID- 11575143
TI  - [Morphological variability and placental function].
AB  - In mammals, the blastocyst defines with the maternal organism, a structure which
      allows embryonic development during gestation: the placenta. The structure of
      this organ varies remarkably across species. In this review the different type of
      placentation have been described in a comparative manner using terms of
      classification such as: placental materno-fetal interdigitation, matemofetal
      blood flow interrelationships, layers of the placental interhemal barrier,
      trophoblast invasiveness and decidual cell reaction, formation of
      syncytiotrophoblast. The human hemomonochorial placenta is characterized by a
      strong decidualization of the uterus and a major invasiveness of the extravillous
      trophoblast. Furthermore, there is a spectrum of placental endocrine activities
      across species. In some mammals (e.g., mouse and rat) the placenta eclipses the
      pituitary in the maintenance of ovarian function. In the human and in the sheep,
      horse, cat and guinea pig, the placenta acquires the ability to substitute for
      the ovaries in the maintenance of gestation at various time during pregnancy. The
      human placenta is characterized by a high rate of steroidogenesis (progesterone
      and estrogens) and by the production of a primate specific trophoblastic hormone:
      human chorionic gonadotropin (hCG). Recently, it was demonstrated that mutation
      of many genes in mice results in embryonic mortality or fetal growth restriction,
      due to defects in placental development. Furthermore, distinct molecular pathways
      regulate the differentiation of various trophoblast cell subtype of the mouse
      placenta. An important question is whether or not placental differentiation in
      other mammals is regulated by the same molecular mechanisms. Due to the striking
      diversity in placental structure, endocrine function and gene expression, caution
      must be exercised in extrapolating findings regarding placental function and
      development from one species to another.

PMID- 11575144
TI  - [The 2 differentiation pathways of the human trophoblast].
AB  - The trophoblast is the major component of the human placenta. It is directly
      involved in blastocyst implantation and in feto-placental growth and development.
      Human trophoblast follows two major pathways of differentiation: the villous
      trophoblast, bathing in maternal blood of intervillous spaces and involved in
      matemo-fetal exchanges and in placental endocrine functions; the extra-villous
      trophoblast involved in uterine spiral arteries remodeling and in the placental
      anchorage into the uterine wall. It is essential to understand the cellular and
      molecular mechanisms involved in human trophoblast differentiation: cellular
      proliferation, migration, invasion and differentiation by cell-cell fusion.
      Abnormal trophoblast differentiation is implicated in the major pathologies of
      human pregnancy such as pre-eclampsia and intrauterine growth retardation.

PMID- 11575145
TI  - Maternal vascularisation of the human placenta: does the embryo develop in a
      hypoxic environment?
AB  - Compared to other mammals, implantation in the human establishes a precocious and
      intimate apposition between the maternal and fetal tissues. In the past it has
      been assumed that this relationship permits early onset of haemotrophic exchange,
      which in turn confers evolutionary advantage by supporting higher development.
      However, there is now strong evidence from a number of different disciplines to
      suggest that human pregnancy comprises two contrasting periods. During the first
      trimester there is little maternal bloodflow to the placenta, the oxygen tension
      within the feto-placental unit is low, and the uterine glands may provide much of
      the nutrient supply. At the start of the second trimester the maternal
      circulation within the intervillous space becomes fully established, the oxygen
      tension rises and haemotrophic nutrition becomes dominant. During the transition
      period there is a period of placental oxidative stress, and the response of the
      tissues to the changing oxygen concentration may play a pivotal role in
      determining the success or otherwise of the pregnancy.

PMID- 11575146
TI  - [Uteroplacental vascularization].
AB  - The intervillous space is considered as receiving the most important part of the
      uterine flow input (> 90%), reaching the placenta through the modified spiral
      arteries network. The low vascular resistance detected on the uterine arteries is
      thought to be due to the presence of the placental shunt. Using a 3D Colour
      Doppler technology (ATL 5000), a complex anastomotic and intra-myometrial network
      has been detected. This vascular network is always detected during the first 48
      hours of after delivery. During this time, the placenta has been removed, the
      uterine muscle is contracted, a low resistance of the uterine flow is
      systematically detected. A extraplacental vascular component must be considered
      as taking a functional part in the foeto-maternal exchanges.

PMID- 11575147
TI  - [Regulation of fetal placental circulation].
AB  - The development and the reactivity of fetoplacental circulation appear to be
      extremely well coordinated phenomena which follow a precise chronology and are
      regulated by numerous angiogenic and vasoactive factors. The endothelium of the
      villous vessels, due to its capacity to release vasodilatating substances, would
      appear to play a crucial role in the gradual decrease in the vascular resistance
      of the placenta, thereby enabling it to meet the growing needs of the fetus right
      up until the end of pregnancy. In the endothelium, as in the smooth muscle of the
      placental vessels, control of production and mechanisms of action of the signal
      modulators of placental tone--endothelin 1, nitric oxide, prostanoids, etc.--as
      well as their dependence on oxygen, are far from being entirely elucidated. The
      study of their interactions could contribute to better evaluating the relative
      importance of each of them in the particular balances which are established at
      different stages of normal pregnancy, as well as during pathological situations
      (pre-eclampsia, intrauterine growth retardation, etc.) when placental blood flow
      and fetal development are at risk of being compromised.

PMID- 11575148
TI  - The pathogenesis of pre-eclampsia.
AB  - Syncytiotrophoblast normally sheds redundant placental debris into the maternal
      circulation, a process, which depends on apoptosis. It is renewed from the
      underlying mononuclear cytotrophoblast. We propose that the continual clearance
      of this debris from the maternal circulation causes a systemic inflammatory
      response that is present in all pregnant women in the third trimester. Pre
      eclampsia occurs when the systemic inflammatory response decompensates. This may
      occur if the burden of the debris is abnormally high, or if the woman's response
      to the process is excessive. There is evidence that oxidative stress in the
      placenta could lead to an overload of debris by stimulating apoptosis or necrosis
      or both. Such stress would be most likely with spiral artery disease either from
      deficient placentation or acute atherosis, In this model, deficient placentation
      is not the cause of pre-eclampsia but a powerfully predisposing condition.

PMID- 11575149
TI  - [HLA molecules, immunity and gestation].
AB  - During pregnancy, the fetus develops particularly efficient molecular regulatory
      mechanisms to prevent possible maternal anti-paternal alloimmune response and
      avoid viral spreading from maternal tissue. Among the different mechanisms, there
      has been noted a selective expression of HLA molecules on trophoblast cells: the
      absence of HLA class II and of polymorphic HLA-A and HLA-B expression but
      presence of both non polymorphic HLA-G and HLA-E class Ib as well as of HLA-C
      class Ia. The functional consequences of such a particular pattern of HLA
      expression in gestation are examined here.

PMID- 11575150
TI  - [Placental hormones and fetal growth].
AB  - Fetal growth is controlled by the placenta which mediates fetal nutritional
      supplies. During pregnancy, the placenta secretes a specific placental growth
      hormone which replaces the pituitary growth hormone in the maternal circulation.
      Placental growth hormone is one example of the materno-placental cooperation
      which is impaired in cases of intra-uterine growth retardation.

PMID- 11575151
TI  - [Placental leptin and pregnancy pathologies].
AB  - Leptin, the protein encoded by the Ob gene, is produced by the white adipose
      tissue and by the placenta during pregnancy. Placental leptin production makes a
      substantial contribution to maternal circulating levels during pregnancy which
      rapidly decrease and return to normal after delivery. Leptin has been detected in
      fetal plasma as early as week 18 of gestation, and umbilical leptin
      concentrations are closely related to birth weight. This has led to the
      hypothesis that fetal fat mass mainly determines fetal circulating leptin.
      Placental leptin production is increased in choriocarcinoma, preeclampsia and
      type 1 diabetes. Estrogens, hypoxia and insulin have been suggested as positive
      regulators of placental leptin production. Maternal leptinemia might act as a
      sensor of energy balance during pregnancy. The presence of both leptin and leptin
      receptors in the placenta suggests that leptin can act by autocrine or endocrine
      pathways in the human placenta. The roles of fetal leptin and consequences of
      increased placental leptin production in pathological pregnancies have yet to be
      elucidated.

PMID- 11575152
TI  - [Placenta and trisomy 21].
AB  - Trisomy 21 is the most frequent genetic anomaly leading to mental retardation,
      and is prenatally diagnosed by fetal karyotyping usually performed on amniotic
      fluid cells. Amniocentesis is offered to patients according to three criteria:
      maternal age (over 38 years), fetal anomalies detected by ultrasonography, and
      abnormal maternal serum markers most of which are produced by the placenta.
      Placental development in trisomy 21 is poorly understood. We therefore studied
      the syncytiotrophoblast, which plays a key role in pregnancy through its
      involvement in fetal-maternal exchanges and in the secretion of pregnancy
      specific hormones. The multinucleated syncytiotrophoblast is formed by the
      differentiation and fusion of mononucleated cytotrophoblasts. We show that in
      trisomy 21, syncytiotrophoblast formation is defective and/or delayed. This
      anomaly is associated with defective synthesis and the secretion of pregnancy
      specific hormones. These findings enhance the understanding of placental serum
      markers used in the prenatal screening of trisomy 21 and clarify the impact of
      placental abnormalities on fetal development in trisomy 21.

PMID- 11575153
TI  - [Placental metastasis of breast cancer].
AB  - The authors report an unusual case of extensive placental micrometastases of
      breast carcinoma occurring in a 43 years-old woman, seen at 31 weeks gestation
      with metastatic disease. A female infant was delivered by caesarean section.
      Physical examination of the newborn was normal. The mother rapidly died of
      metastatic disease. Placental metastases from maternal tumours are rarely
      reported in the literature. The diagnosis is made by histologic examination.
      Placental metastases are associated with bad prognosis for the mother. The foetus
      is usually free of tumours when the metastases are limited to the intervillous
      space.

PMID- 11575154
TI  - [The intrauterine contraceptive implant without armature].

PMID- 11575155
TI  - [Intrauterine insemination or fertilization in vitro? Intrauterine insemination:
      when is it necessary to choose fertilization in vitro?].

PMID- 11575156
TI  - [Intrauterine insemination of fertilization in vitro? Why choose intrauterine
      insemination first in most situations?].

PMID- 11575157
TI  - The regulation of eIF4F during cell growth and cell death.

PMID- 11575158
TI  - Phosphorylation of mammalian eIF4E by Mnk1 and Mnk2: tantalizing prospects for a
      role in translation.

PMID- 11575159
TI  - Control of translation by the target of rapamycin proteins.

PMID- 11575160
TI  - Regulation of the activity of eukaryotic initiation factors in stressed cells.

PMID- 11575161
TI  - Initiation factor eIF2 alpha phosphorylation in stress responses and apoptosis.
AB  - The alpha subunit of polypeptide chain initiation factor eIF2 can be
      phosphorylated by a number of related protein kinases which are activated in
      response to cellular stresses. Physiological conditions which result in eIF2
      alpha phosphorylation include virus infection, heat shock, iron deficiency,
      nutrient deprivation, changes in intracellular calcium, accumulation of unfolded
      or denatured proteins and the induction of apoptosis. Phosphorylated eIF2 acts as
      a dominant inhibitor of the guanine nucleotide exchange factor eIF2B and prevents
      the recycling of eIF2 between successive rounds of protein synthesis. Extensive
      phosphorylation of eIF2 alpha and strong inhibition of eIF2B activity can result
      in the downregulation of the overall rate of protein synthesis; less marked
      changes may lead to alterations in the selective translation of alternative open
      reading frames in polycistronic mRNAs, as demonstrated in yeast. These mechanisms
      can provide a signal transduction pathway linking eukaryotic cellular stress
      responses to alterations in the control of gene expression at the translational
      level.

PMID- 11575162
TI  - Elongation factor-2 phosphorylation and the regulation of protein synthesis by
      calcium.

PMID- 11575163
TI  - Insulin signaling and the control of PHAS-I phosphorylation.

PMID- 11575164
TI  - The p70 S6 kinase integrates nutrient and growth signals to control translational
      capacity.

PMID- 11575165
TI  - Regulation of translation initiation by amino acids in eukaryotic cells.
AB  - The translation of mRNA in eukaryotic cells is regulated by amino acids through
      multiple mechanisms. One such mechanism involves activation of mTOR (Fig. 1).
      mTOR controls a myriad of downstream effectors, including RNA polymerase I, S6K1,
      4E-BP1, and eEF2 kinase. In yeast, and probably in higher eukaryotes, mTOR
      signals through Tap42p/alpha 4 to regulate protein phosphatases. Through
      phosphorylation of Tap42p/alpha 4, mTOR abrogates dephosphorylation of the
      downstream effectors by PP2 A and/or PP6, resulting in their increased
      phosphorylation. Although at this time still speculative, in vitro results using
      mTOR immunoprecipitates suggest that mTOR, or an associated kinase, may also be
      directly involved in phosphorylating some effectors. Enhanced RNA polymerase I
      activity results in increased transcription of rDNA genes, whereas increased S6K1
      activity promotes preferential translation of TOP mRNAs, such as those encoding
      ribosomal proteins. Together, stimulated RNA polymerase I and S6K1 activities
      enhance ribosome biogenesis, increasing the translational capacity of the cell.
      Phosphorylation of 4E-BP1 prohibits its association with eIF4E, allowing eIF4E to
      bind to eIF4G and form the active eIF4F complex. Increased eIF4F formation
      preferentially stimulates translation of mRNAs containing long, highly-structured
      5' UTRs. Finally, amino acids cause inhibition of the eEF2 kinase, resulting in
      an increase in the proportion of eEF2 in the active, dephosphorylated form. By
      inhibiting eEF2 phosphorylation, amino acids may not only stimulate translation
      elongation, but may also prevent activation of GCN2 by enhancing the rate of
      removal of deacylated tRNA from the P-site on the ribosome; a potential activator
      of GCN2. GCN2 may also be regulated directly by the accumulation of deacylated
      tRNA caused by treatment with inhibitors of tRNA synthetases or in cells
      incubated in the absence of essential amino acids. However, because the Km of the
      tRNA synthetases for amino acids is well above the amino acid concentrations
      found in plasma of fasted animals, such a mechanism may not be operative in
      mammals in vivo. Activation of GCN2 results in increased phosphorylation of the
      alpha-subunit of eIF2, which in turn causes inhibition of eIF2B. Thus, by
      preventing activation of GCN2, amino acids preserve eIF2B activity, which
      promotes translation of all mRNAs, i.e., global protein synthesis is enhanced.

PMID- 11575166
TI  - Insulin, phorbol ester and serum regulate the elongation phase of protein
      synthesis.

PMID- 11575167
TI  - Regulation of protein synthesis by insulin through IRS-1.

PMID- 11575168
TI  - Regulation of eukaryotic initiation factor eIF2B.

PMID- 11575169
TI  - A classroom mind/body wellness intervention for older adults with chronic
      illness: comparing immediate and 1-year benefits.
AB  - The authors tested the efficacy of a mind/body wellness intervention for older
      adults with chronic illness. They randomly assigned 243 physician-referred
      patients from an urban HMO to a classroom intervention or a wait-list control
      group. The intervention provided instruction on mind/body relationships;
      relaxation training; cognitive restructuring; problem-solving; communication; and
      behavioral treatment for insomnia, nutrition, and exercise. At posttreatment, the
      intervention group had significant decreases in self-reported sleep difficulties,
      pain, anxiety, and depression symptoms compared with controls. The intervention
      also led to a significant decrease in "chance" and "powerful others" health locus
      of control beliefs. At 1-year follow-up, the intervention group maintained
      benefits in sleep and health locus of control and also reported a significant
      increase in health behaviors compared with controls. Pain, anxiety, and
      depression benefits were not maintained. This type of classroom intervention
      appears to have some lasting effects on health behaviors and beliefs.

PMID- 11575170
TI  - Type A behavior pattern today: relevance of the JAS-S factor to predict heart
      rate reactivity.
AB  - The authors used 89 undergraduate students' scores in the S-factor of the Jenkins
      Activity Survey, a measure of speed and impatience, to classify 45 participants
      as high scorers and 44 as low scorers. They then measured the students' tonic and
      phasic heart rates during an examination, a genuinely stressful situation. The
      experiment consisted of three phases: adaptation, task, and recovery. The
      findings confirmed the authors' hypothesis that the high-S scorers would show
      higher cardiac reactivity values than the low-S scorers. The authors also
      observed that the high-S scorers took more time than the low-S scorers to recover
      their initial heart rate values after being exposed to the stress situation. This
      finding led the authors to suggest that each group may have different response
      patterns. They call for further research on individuals with "fast activation
      fast recovery" and "fast activation-slow recovery" profiles.

PMID- 11575171
TI  - Are biomarkers a useful aid in smoking cessation? A review and analysis of the
      literature.
AB  - Healthcare providers' ability to motivate people to try to quit smoking or to
      remain abstinent is limited. Even with our best treatments, most smokers relapse
      within 1 year. Therefore it is important that we constantly strive to develop and
      test new, effective smoking interventions. Providing feedback on one's biomarkers
      (e.g., biological indices of smoking-related harm, harm exposure, or genetic
      susceptibility to disease) have been suggested as potentially useful for
      increasing smokers' motivation or ability to quit smoking. In fact, variations of
      this strategy are commonly incorporated into behavioral smoking-cessation
      interventions, but little empirical evidence has specifically addressed whether
      this approach is effective. In this article, the author reviews the theoretical
      rationale and empirical evidence regarding this practice. Although the
      preliminary evidence is promising, more research is needed to determine the
      efficacy of using biomarkers and the limits of the strategy's effectiveness.
      Future investigations should address these issues.

PMID- 11575172
TI  - Mental models of women with breast implants: local complications.
AB  - Twenty-five women with breast implants participated in semistructured interviews
      designed to reveal their "mental models" of the processes potentially causing
      local (i.e., nonsystemic) problems. The authors analyzed their responses in terms
      of an "expert model," circumscribing scientifically relevant information. Most of
      the women interviewed had something to say about most elements in the expert
      model. Nonetheless, gaps in their mental models undermined decision making about
      their implants. One woman misunderstood the terms used by the medical community
      to describe implant failure (e.g., rupture, leak, and bleed). Another exaggerated
      the implants' vulnerability to direct impacts, such as car accidents.
      Participants also overestimated their ability to detect localized problems and to
      select medical remedies. Although they were generally satisfied with their own
      implants, many participants were dissatisfied with the decision-making processes
      that lead to their choice. Their interviews are interpreted by the form and
      content of communications that women with implants need to help them manage their
      health decisions better.

PMID- 11575173
TI  - [The evolution of quinolone: from nalidixic acid to the quinolones of the third
      generation].

PMID- 11575174
TI  - [Action and reaction. Actions and resistance mechanisms of quinolone].

PMID- 11575175
TI  - [How do we use quinolones? Indications from the viewpoint of clinical
      microbiology].

PMID- 11575176
TI  - [How are quinolones used in clinical practice? Gyrase antagonists from the
      viewpoint of the hospital pharmacist].

PMID- 11575177
TI  - [What should be used for salmonella and company? Antibiotic therapy for bacterial
      diarrhea].

PMID- 11575178
TI  - [Well tolerated or risky? Adverse effect of quinolones].

PMID- 11575179
TI  - [How well do gyrase inhibitors work? The pharmacokinetics of quinolones].

PMID- 11575180
TI  - [Caution with methylxanthines, antacids or warfarin! Drug interactions with
      quinolones].

PMID- 11575181
TI  - [How can we protect against broad-band pathogens? The situation with quinolone
      resistance].

PMID- 11575182
TI  - [Where are quinolones going? New agents in development].

PMID- 11575183
TI  - [Quinolones in the environment: biological breakdown of gyrase inhibitors].

PMID- 11575184
TI  - Adaptation to night shifts and synchronisation processes of night workers.
AB  - Human beings are accustomed to being active and awake during the day, and asleep
      and rest at night. Since we live in a society which is organised predominantly
      along daytime activity, therefore working in the night shift may deeply disrupt
      our social and family life. It is also a well-known fact that night shift causes
      fatigue and circadian disruption. The basic manifestation of fatigue and
      circadian rhythm has been linked to health and safety problems, involving
      decrements in psychophysical and physiological functions, plus subjective
      complaints. In this context quantitative relationships between shift work and
      circadian rhythm need to be assessed to explore suitable time schedule, and to
      minimise sleep depth and fatigue. There is also a great need to discuss circadian
      disruption, sleepiness and the increasing cost of work related illness among
      night workers. In this regard, some aspects of fatigue and circadian disruption
      caused from night shift work are revealed in this paper aiming to increase
      workers' health, safety and well being as well as productivity. Light/dark cycle
      and social stimuli issues acting on the circadian timing systems are also
      explored to solicit opinions and discussion on the controversy of night work.
      Suggestions are therefore likewise given to enhance workers' adaptation to night
      shift and synchronization process.

PMID- 11575185
TI  - Characteristics of body heat balance of paraplegics during exercise in a hot
      environment.
AB  - The purpose of this investigation was to clarify the characteristics of body
      temperature regulation in paraplegics due to spinal cord injury (SCI) during an
      arm cranking exercise in a hot environment. Twelve paraplegics with lesions
      located between Th3 and L1,2 and seven able-bodied subjects (AB) participated in
      this study. The subjects were exposed to a hot (33 degrees C) or a moderate
      temperature (25 degrees C) environment for one hour and during the last 10 min of
      the exposure, the subjects performed arm cranking exercises at an exercise
      intensity of 40 W. The skin temperatures at the chest, the upper arm, the thigh
      and the calf, the tympanic membrane temperature (Tty), and the skin blood flow of
      the thigh (SBFT) were continuously monitored during the experiment. Although no
      systematical variation was found in the Tty at 25 degrees C, the Tty at 33
      degrees C in paraplegics during exercise was significantly greater than that at
      rest (P < 0.01), which indicated a pronounced heat stress for paraplegics at 33
      degrees C. SBFT of paraplegics with high lesions of the SCI remained unchanged
      during the experiment at 25 degrees C and 33 degrees C, while paraplegics with
      low lesions in this study showed consecutive increases in SBFT during exercise in
      both environmental conditions similar to AB. The increased core temperature in
      paraplegics with high lesions was considered to be due to a lack of sweat
      response and vasomotor activity in the paralyzed area. On the basis of the
      findings in this study, it can be suggested that high core temperature without
      any increment of SBFT may be characterized as body heat balance of paraplegics
      with high lesions during exercise in a hot environment.

PMID- 11575186
TI  - The effect of short-term (10- and 15-min) running at self-selected intensity on
      mood alteration.
AB  - The primary purpose of this study was to contrast the effects of two short
      duration exercises on mood changes. A secondary goal was to examine the
      relationship between pre-exercise and post-exercise mood states. The subjects
      were 15 healthy male graduate students. They were involved in a within-subject
      design in which each individual completed two trials of running on a treadmill,
      one trial for 10 minutes and the other for 15 minutes. The Mood Checklist Short
      form 1 (MCL-S1) used in the present study represents the participants' mood
      states before, during, and after exercise. This questionnaire has three sub
      scales measuring (a) pleasantness, (b) relaxation, and (c) anxiety. Participants
      ran on a treadmill for the assigned time at a self-selected intensity after being
      told to run at a rate that felt good and was not painful. ANOVA results showed
      that both of the short bouts of exercise affected the subjects' mood, because the
      main effect of time spent exercising was observed in all sub-scales of the MCL-S1
      and there were no significant differences in trial-by-time interaction. In
      addition to these results, there was a significant correlation between the two
      trial lengths in the amount of pleasantness and the amount of anxiety felt at
      post-exercise. There were moderate differences in the effect size (ES) for pre-
      and post-exercise pleasantness and anxiety levels. These results revealed similar
      patterns of change. It seems reasonable to conclude, based on this study, that
      exercise between 10 and 15 minutes results in similar psychological benefits for
      the person exercising.

PMID- 11575187
TI  - A comparative study of foot dimension between adult male and female and
      evaluation of foot hazards due to using of footwear.
AB  - Using footwear often becomes troublesome and creates many problems. Most of these
      problems are associated with the wearing of ill-fitting footwear, as it leads to
      biomechanical imbalance and ultimately give rise to different foot problems. In
      the present investigation different foot problems, viz., discomfort, pain and
      other hazards related to the use of footwear have been evaluated and attempts
      have been made to study different foot dimensions of men and women that are
      related to the design of footwear. For the present study different foot
      dimensions of both right and left feet of the subjects were measured on 300
      Bengalee (Indian) subjects having the age range of 20-35 years. The subjects
      reported that they had got discomfort, pain, blister and corn due to using
      different footwear. It was noted that the occurrence of these problems in right
      foot was greater than that in left foot. There was no significant correlation
      between foot troubles and type of footwear. Results also showed that there was no
      significant difference in most of the foot dimensions between left foot and right
      foot. However, significant difference (P < 0.001) in all foot dimensions was
      observed between male and female subjects. Correlation coefficient among
      different foot dimensions has also been evaluated and it was noted that foot
      length was highly correlated with stature and foot volume, particularly in left
      foot. Footwear should be made according to the foot dimensions of the user
      population. The database collected from the Bengalee (Indian) population may be a
      helpful guide for manufacturing different footwear.

PMID- 11575188
TI  - Evaluation of disuse atrophy of rat skeletal muscle based on muscle energy
      metabolism assessed by 31P-MRS.
AB  - The purpose of this study was to evaluate disuse atrophy of skeletal muscle using
      a hind-limb suspension model, with special reference to energy metabolism. Twenty
      four Sprague-Dawley rats were divided into four groups: control group (C), hind
      limb suspended for 3 days (HS-3), for 7 days (HS-7) and for 14 days (HS-14). The
      gastrocnemius-plantaris-soleus (GPS) muscles in each group were subjected to the
      following measurements. After a 2-min rest, contraction of the GPS muscles was
      induced by electrical stimulation of the sciatic nerve at 0.25 Hz for 10 min,
      then the frequency was increased to 0.5 and 1.0 Hz every 10 min. During the
      stimulation, twitch forces were recorded by a strain gauge, and 31P-MRS was
      performed simultaneously. Maximum tension was measured at the muscle contraction
      induced at 0.25 Hz; the wet weight of the whole and each muscle in the GPS
      muscles was also measured. From the 31P-MR spectra during muscle contraction, the
      oxidative capacity was calculated and compared among the groups. The weights of
      the whole GPS muscles in C, HS-3, HS-7 and HS-14, were 2.66 +/- 0.09, 2.39 +/-
      0.21, 2.34 +/- 0.21 and 2.18 +/- 0.14 (g) respectively. Thus, the muscle mass
      significantly decreased with time (p < 0.05). Among the GPS muscles, the decrease
      in weight of the soleus muscle was especially remarkable; in the HS-14 group its
      weight decreased to 60% of that in the C group. We evaluated maximum tension and
      oxidative capacity as the muscle function. The maximum tensions in C, HS-3, HS-7
      and HS-14 were 519 +/- 43, 446 +/- 66, 450 +/- 23 and 465 +/- 29 (g),
      respectively. This was significantly greater in the C group than in any other
      groups, however there were no significant differences among the three HS groups.
      The oxidative capacity during muscle contraction in the C group was higher than
      in any HS group and it did not further decrease even if the suspension of the
      limbs was prolonged beyond 3 days. The present study showed that in disuse
      atrophy, muscle mass and muscle function did not change simultaneously. Thus, it
      is necessary to develop countermeasures to prevent muscle atrophy and muscle
      function deterioration independently.

PMID- 11575189
TI  - The challenges of neuropathic pain.

PMID- 11575190
TI  - Osteoarthritis of the temporomandibular joint organ and its relationship to disc
      displacement.
AB  - To overcome disagreements with regard to the relationship between disc
      displacement and osteoarthritis of the temporomandibular joint (TMJ), the
      evidence for suggested disease mechanisms and clinical course of these disorders
      is reviewed. The TMJ behaves as a complex organ in which biochemical and
      biomechanical processes regulate the physiology of cartilage, bone, synovium,
      ligaments, and synovial fluid. In this concept, TMJ osteoarthritis is an organ
      failure involving all its structures. The development of as well as recovery from
      disease appears to be intimately related to exceeding and supporting the adaptive
      capacity of the tissues that make up the joint organ. Loss of fibrocartilage and
      inflammation appear to be major pathobiologic processes, while serious doubts
      exist about the significance of disc position in joint pathology.

PMID- 11575191
TI  - The influence of experimentally induced osteoarthrosis on articular nerve fibers
      of the sheep temporomandibular joint.
AB  - AIMS: To study the effect of experimentally induced osteoarthrosis, or non
      inflammatory degenerative changes, on the innervation of the sheep
      temporomandibular joint (TMJ) through the use of indirect immunohistochemistry
      and image analysis quantification. METHODS: Bilateral condylar scarification was
      performed in 8 sheep, which were killed at 16 weeks post-operation; 3 unoperated
      sheep served as controls. Tissues from 8 osteoarthrotic joints and 4 control
      joints were processed for the immunostaining with antisera for protein gene
      product 9.5 (PGP 9.5), substance P (SP), calcitonin gene-related peptide (CGRP),
      neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and tyrosine
      hydroxylase (TH). An additional 10 joints were decalcified to study the
      morphologic changes induced by the condylar abrasion. RESULTS: Osteoarthrotic
      changes were commonly seen in the anterior and lateral regions of the joint and
      included fibrosis, peripheral osteophyte formation, cysts, and erosion of
      articular surfaces. In the osteoarthrotic joints, the distribution of PGP 9.5-,
      CGRP-, and SP-immunoreactive (IR) nerve fibers was similar to that observed for
      control joints in the capsule, synovium, and capsule/disc junction. There were
      statistically detectable decreases in the percent surface area of IR nerve fibers
      in the capsule for both PGP 9.5 and CGRP in arthrotic joints compared with
      control joints. The lateral and anterior regions of the capsule had greater
      density of PGP 9.5- and CGRP-IR nerve fibers than other parts of the capsule in
      both control and arthrotic joints, and the medial capsule was poorly innervated
      in all joints. Immunostaining for substance P was always weaker. CONCLUSION: This
      study suggests that while inflammatory arthritis has a marked influence on the
      density of sensory and autonomic nerve fibers in synovium in a variety of joints
      in different species, experimentally induced non-inflammatory osteoarthrosis in
      the sheep TMJ also leads to a depletion of the density of nerve fibers in the
      capsule, especially in the lateral part of the joint. Further work is required to
      determine whether other parts of the joint, such as synovium and marrow, respond
      differently to experimentally induced osteoarthrosis.

PMID- 11575192
TI  - Psychosocial functioning and dental factors in adolescents with temporomandibular
      disorders: a case-control study.
AB  - AIMS: To examine the influence of psychosocial functioning and dental factors in
      adolescents with temporomandibular disorders (TMD) versus healthy subjects.
      METHODS: The TMD sample comprised 63 patients (21 boys and 42 girls, 33% and 67%,
      respectively, with a mean age of 14.9 years; range 12 to 18 years) and was
      compared with 64 healthy control subjects (17 boys and 47 girls, 27% and 73%,
      respectively, with a mean age of 14.8 years). Subjects in the TMD group had to
      report pain once a week or more and to have a TMD pain diagnosis according to the
      Research Diagnostic Criteria for TMD. Participants were clinically examined and
      filled out a questionnaire in which self-reported psychosocial functioning was
      assessed on standardized measures, including the Youth Self-Report (YSR), somatic
      complaints, and stress. RESULTS: No significant differences were found in dental
      factors among adolescents in the TMD group compared with those in the control
      group. Multiple pains in the body and fatigue were significantly more common in
      the TMD group compared with the control group. Adolescents with TMD also reported
      significantly higher levels of stress, somatic complaints, and aggressive
      behavior than their counterparts in the control group. In particular, young
      adolescents with TMD reported high levels of psychosocial problems. CONCLUSION:
      In adolescents with TMD, psychosocial factors such as increased levels of stress,
      somatic complaints, and emotional problems seem to play a more prominent role
      than dental factors.

PMID- 11575193
TI  - Prevalence of symptoms associated with temporomandibular disorders in Hong Kong
      Chinese.
AB  - AIMS: To estimate the prevalence of self-reported symptoms associated with
      temporomandibular disorders (TMD) and treatment-seeking in adult Chinese in Hong
      Kong. METHODS: A telephone survey technique was used to identify 1,526 randomly
      selected Cantonese-speaking individuals aged 18 years or over. Standard questions
      were asked about joint and jaw muscle pain, jaw opening, and joint sounds. In
      addition, questions on tooth grinding and clenching, sleep patterns, and
      treatment-seeking behavior were posed. RESULTS: Jaw pain was reported by 33% of
      the population. Only 5% of them had frequent pain, with two thirds of this
      subgroup having moderate to severe symptoms. The prevalence of frequent problems
      with jaw opening and joint clicking was 0.3% and 1.8%, respectively. There were
      no gender-related differences in the reporting of TMD symptoms or related
      conditions. CONCLUSION: One percent of the Hong Kong Chinese population had TMD
      related jaw pain that was of moderate or severe intensity and occurred
      frequently; 0.6% of the population had sought treatment for jaw pain, impaired
      jaw opening, or joint clicking that occurred often in the previous year.

PMID- 11575194
TI  - Preliminary psychologic survey of orofacial outpatients. Part 1: Predictors of
      anxiety or depression.
AB  - AIMS: To identify predictors for anxiety and depression in orofacial outpatients
      and to investigate the patients' compliance rate in taking a series of
      psychologic tests. METHODS: Three thousand six hundred sixty-six patients
      completed a battery of questionnaires. These consisted of items inquiring about
      sex, age, past history of disease, presence of pain, the Hospital Anxiety and
      Depression Scale (HADS), the Eysenck Personality Questionnaire Short Form (S
      EPQ), a Japanese dental version of the McGill Pain Questionnaire (JDMPQ), a
      visual analog scale (VAS) of pain, pain duration, and diagnosis. After univariate
      analyses had determined those variables with significant differences between an
      over-probable group (OPG, HADS scores > or = 8) and an absent group (AG, HADS
      scores < 8), we estimated the odds ratios of these variables for OPG as
      independent variables, and every variable was adjusted between the independent
      variables by multiple logistic regression models. RESULTS: For anxiety, 3
      variables were independently related to the OPG and considered to be meaningful:
      age 30 or older, neuroticism score on the S-EPQ, and selection of the JDMPQ pain
      expression term "sickening." For depression, 4 variables were independently
      related to the OPG and considered to be meaningful: age 30 or older, neuroticism
      and extroversion scores on the S-EPQ, and selection of the JDMPQ pain expression
      term "sickening." The compliance rate for the tests was under half of the
      patients (3,666 of 7,542 patients). CONCLUSION: Although the predictability for
      anxiety or depression by some baseline parameters is considered to be low, age,
      personality traits, and choice of certain pain expression terms are useful
      predictors of anxiety or depression. The improvement of the compliance rate for
      psychologic screening will be a future challenge for Japanese clinics managing
      orofacial patients.

PMID- 11575196
TI  - Space maintenance in the transitional dentition.

PMID- 11575195
TI  - Effect of jaw muscle pain and soreness evoked by capsaicin before sleep on
      orofacial motor activity during sleep.
AB  - AIMS: Sleep bruxism, which is a form of orofacial motor activity (OMA), and jaw
      muscle pain and soreness have for a long time been thought to be mutually linked.
      The aim of this study was to investigate the effect of clinical and experimental
      jaw muscle pain and soreness on sleep OMA. METHODS: Twelve healthy subjects aged
      21 to 31 years old participated in this study. All of them were aware of signs or
      symptoms of sleep OMA and were subdivided into a group with clinical pain
      complaints (n = 5) and a group without pain (n = 7). All subjects slept in the
      laboratory for 3 consecutive nights, including a habituation night, a baseline
      night, and an experimental night. Electroencephalographic (EEG) activity and
      electromyographic (EMG) activity from the masseter muscles were recorded during
      sleep. On the experimental night, before sleep, all subjects received an
      injection of capsaicin (0.1 mL, 100 micrograms/mL) into the masseter muscle that
      had demonstrated the most EMG activity during the previous recordings. The OMA
      events and episodes were quantified and were compared between the baseline night
      and the experimental night. Every evening and morning during the study period,
      pain intensity, unpleasantness, and soreness were scored by the subjects on a
      visual analog scale (VAS), and pain detection thresholds (PDTs) in the masseter
      muscles and maximal voluntary occlusal force (MVOF) were also measured. RESULTS:
      Pre-sleep injection of capsaicin did not cause significant differences between
      groups in peak pain intensity on the VAS. The PDT and MVOF did not show any
      significant differences between groups, injection and non-injection sides, or
      baseline and experimental nights and mornings. The number of EMG episodes/hour
      sleep, the number of bursts/hour sleep, and total area of all bursts and episodes
      during the baseline night were significantly higher in the subjects without pain
      than in the subjects with pain. However, the capsaicin injection did not cause
      any significant changes in these parameters. CONCLUSION: This study suggests that
      an acute pre-sleep painful stimulus does not have any effect on OMA during sleep,
      but the study extends previous findings that clinical jaw muscle pain and
      soreness are associated with less EMG activity in the masticatory muscles.

PMID- 11575197
TI  - The professional.

PMID- 11575198
TI  - 116 years of practice experience: wit and wisdom from two Muskogee practitioners.
      Interview by Sidney Nicholson.

PMID- 11575199
TI  - [Doppler echocardiographic study of arterial distensibility. Comparison with
      ambulatory arterial pressure monitoring].
AB  - Echocardiography Doppler (ED) is a common tool in hypertension to assess left
      ventricular (LV) mass or LV function. Echography doppler is also available to
      assess some arterial distensibility (AD) indexes, but it is less frequently used.
      The aim of this study is to compare AD indexes obtained from echographie doppler
      with timing of Korotkoff sound (QKd interval), obtained from ambulatory blood
      pressure monitoring (APM). Sixty-two patients with or without cardiac diseases
      were prospectively enrolled, except those with left bundle branch, atrial
      fibrillation or pacemaker. Echography doppler study collected timing of abdominal
      pulse (QtAA), interval time between Q ECG and the foot of doppler wave velocity
      in abdominal aorta pulse wave velocity (PWV) between two points of descending
      thoracic aorta; and Stroke index. APM study collected simultaneous usual pressure
      indexes (systolic diastolic, pulse pressure) instantaneous and over 24 h, and QKd
      interval times between Q ECG and diastolic Korotkoff sound instantaneous and over
      24 h. Absolute AD Index (Burton index) was defined as Stroke index/pulse
      pressure. QtAA intra observer variability was the coefficient of variation
      (mean/SD). QtAA inter observer variability was QtAA assessments by two observers.
      RESULTS: QtAA was correlated with QKdi (r = 0.78; p < 0.001) and QKd24 h (r =
      0.64; p < 0.001). PWV was correlated with QKdi (r = 0.35; p = 0.009), but not
      with QKd24 h (r = 0.17; p = 0.24, NS). Burton index was correlated with QKdi (r =
      0.48; p < 0.001), and QKd24 h (r = 0.53; p < 0.001). CONCLUSION: Echography
      doppler may provide some arterial distensibility indexes. Among these indexes,
      QtAA is easy to obtain and well correlated with QKd. However, further studies are
      needed to assess normal and pathological values.

PMID- 11575200
TI  - [Aorta-left ventricular relationship evaluated by Doppler echocardiography and
      ambulatory arterial prsesure monitoring].
AB  - Arterial distensibility is one of the components of afterload. Arterial
      distensibility, left ventricular (LV) mass and LV function are closely linked.
      The aim of this study is to describe the relations between LV mass LV function
      and arterial distensibility evaluated by echography Doppler (echography Doppler)
      and ambulatory monitoring pressure. Sixty-two patients with or without cardiac
      disease were prospectively enrolled excepted those with atrial fibrillation, left
      bundle branch block pace maker, or valvulopathy. Echography Doppler study
      collected stroke volume, LV diameters and wall thickness, ejection time (ET) and
      preejection time (PET); were calculated ejection fraction (EF), systolic
      pressure/systolic diameter ratio, LV mass index (LVMI), relative wall thickness
      ratio (e/r). AMP collected usual pressure datas and QKd, time interval between
      QECG and diastolic Korotkoff sound, instantaneous, over 24 h (i, 24 h), and for a
      pressure of 100 mm Hg and a heart rate of 60 bpm (QKd 100-60). RESULTS: QKd 24 h
      was correlated with LVMI (r = 0.40, p = 0.006) and e/r (r = 0.32, p = 0.028).
      QKdi was correlated with EF (p < 0.001, r = 0.65), with systolic
      pressure/systolic diameter ratio (p < 0.001, r = 0.75), and with ET/PET (r =
      0.56, p < 0.001). When PET was withdrawn from QKd, no correlation exist between
      QKd-PET and LV function index, excepted QKd-PET versus systolic pressure/systolic
      diameter (r = 0.46, p = 0.005). CONCLUSION: QKd is not only an arterial
      distensibility index but also a LV function index, because PET is included in it.
      Echography Doppler and AMP are available and common tools to study the aorta/LV
      relationship.

PMID- 11575201
TI  - [Sensitivity and specificity of criteria of left ventricular hypertrophy for
      predicting cardiovascular complications in the Bordeaux cohort of hypertensive
      patients].
AB  - Left ventricular hypertrophy (LVH) is associated with an increased risk of
      cardiovascular complications independently of other known risk factors. Since
      1983, we have followed up a cohort of initially untreated hypertensive patients
      with echocardiographic measurements of left ventricular mass (LVM). We analyzed
      the data on 474 patients with more than five years' follow-up to assess the
      prognostic value of LVM and the sensitivity and specificity of the different ways
      to index for LVM through ROC curves. Forty patients were lost to follow-up. The
      mean follow-up period was 89 +/- 31 months. A cardiovascular complication was
      recorded in 40 individuals. There was a strong link between increased LVM and the
      occurrence of complications. Indexation by body surface area or height to the
      power 2.7 give the [table: see text] greatest area under the curve (AUC) to
      discriminate between patient with or without cardiovascular events. To get the
      same sensitivity in females and in males for the prediction of future events,
      lower cut-off must be used in females.

PMID- 11575202
TI  - [Inhibition of iron-catalyzed oxidative reactions restores mathcing between
      coronary blood flow and myocardial metabolic demand in type 2 diabetes].
AB  - In diabetes, endothelium-dependent dilation of large and small coronary arteries
      is impaired, which results in a mismatch between myocardial metabolic demand and
      coronary blood flow. It has been proved that deferoxamine, an iron chelator that
      inhibits Fenton and Haber-Weiss reactions, restores a normal response to cold
      pressor test and flow increase in angiographically normal epicardial coronary
      arteries of diabetic patients. This result suggests that nitric oxide could be
      inactivated by reactive oxygen species. The aim of this study was to assess the
      effects of deferoxamine on coronary microcirculation vasomotion when myocardial
      oxygen demand is increased by sympathetic stimulation elicited by cold pressor
      test in type 2 diabetic patients. In 17 patients with angiographically normal
      coronary arteries and without any other coronary risk factors, coronary blood
      flow has been measured using quantitative angiography and intracoronary Doppler
      at baseline and during a cold pressor test, before and after intravenous
      administration of 500 mg deferoxamine. Increase in rate-pressure product, an
      estimate of myocardial metabolic demand, was similar before and after
      deferoxamine (+21.1 +/- 8.7% vs +20.5 +/- 8.9%, respectively), but coronary blood
      flow increase was significantly higher after deferoxamine (+6.3 +/- 12.9% vs
      +31.8 +/- 16.7%, respectively, p < 0.001), and coronary resistance was increased
      before deferoxamine and decreased after (+14.8 +/- 21.9% vs -7.9 +/- 10.9%,
      respectively, p < 0.001). Moreover, before deferoxamine, the negative correlation
      between coronary blood flow and rate-pressure product changes before deferoxamine
      (R = 0.518, P < 0.05) was turned in a positive relationship after deferoxamine (r
      = 0.546, p < 0.05). In conclusion, in type 2 diabetic patients, endothelium
      dependent dilation of the coronary microcirculation is restored when iron
      catalysed oxidative reactions are inhibited by deferoxamine, which restores the
      normal matching between myocardial oxygen demand and coronary blood flow.

PMID- 11575203
TI  - [Frequency and detection rate of silent myocardial ischemia by Holter monitoring
      in patients with stable coronary insufficiency under treatment. Study of 95,725
      recorded hours].
AB  - AIM OF THE STUDY: To determine in standard living conditions the circadian
      variation of the symptomatic and silent electrocardiographic ischaemia in
      patients with chronic stable coronary insufficiency. To evaluate the influence of
      the past history of the patients on the circadian variations of the symptomatic
      and silent ischaemic events. METHODS: The patients included in the study
      presented with stable angina pectoris and have undergone a 96 hours Ambulatory
      ECG (AECG) monitoring with a low-weight and compact material which did not modify
      their daily activities (R-test). The system records the trace that the patient
      has initiated it himself following the onset of symptoms and makes possible to
      distinguish between silent and symptomatic ischaemia. The same experienced
      cardiologist validated all the AECG records. RESULTS: 1,022 patients aged 64.6 +/
      11.0 years suffering of coronary insufficiency from 5.8 +/- 6.0 years have
      undergone an electrocardiographic record by an R-test for a total duration of
      95,725 hours. Of the 1,022 records, 3,258 ischaemic events have been validated:
      295 (9.1%) were symptomatic and 2,963 (90.9%) were silent which correspond to a
      ratio of 1 versus 9 while this ratio is usually described as 1 versus 4. By 26.5%
      (n = 271) of the patients, ischaemia have been detected and among them more than
      a half (54.6%, n = 148) were presenting only silent ischaemia. Of these patients
      who present silent ischaemia, it was recorded during the first 24 hours by only
      63.7% of them which is the usual duration of an ambulatory ECG monitoring. This
      percentage increases to 83.1% after 48 hours and to 94.1% after 72 hours.
      CONCLUSION: By more than one third (36.3%) of the patients with stable coronary
      insufficiency, an ambulatory ECG monitoring recorded during only 24 hours is
      insufficient to detect a silent ischaemia which will happen later. A record
      duration of 48 hours reduces this risk to 20% of the patients and of 72 hours to
      less than 5%.

PMID- 11575204
TI  - [Arterial dysfunction after treatment of coarctation of the aorta].
AB  - The long term follow-up after successful coarctation repair has a late
      cardiovascular morbidity, includes systemic hypertension at rest or/and after
      exercise. The pathophysiology mechanisms responsible have not been well
      determined. We studied 70 normotensive subjects at rest (age, 14 +/- 5 y;
      pressure, 116 +/- 13/56 +/- 9 mmHg), who had an isolated coarctation with a good
      repair defined by the absence of gradient between upper and lower right limb (0.
      26 mmHg). After exercise testing we defined two groups: Coa HT: Hypertension at
      exercise equal or over 200 mmHg, n = 20 (228 +/- 23 mmHg) and Coa HT:
      Normotensive at exercise = 10 (163 +/- 24 mmHg). These subjects were mached sex
      age and blood pressure to 70 controls (age, 13 +/- 3 y; pressure, 115 +/- 10/56
      +/- 6 mmHg). Using a high-resolution echographic technique, we assessed the
      systolic, diastolic diameter and the intima media thickness (IMT) of the common
      carotid artery (CCA) to define mechanical indexes: Cross sectional compliance
      (CSC), distensibility (CSD) and incremental elastic modulus (Einc) in each group.
      CCA pressure waveform and the local pulse pressure were determined in 32 subjects
      to define augmentation index (AI). The changes of the brachial artery diameter in
      response to reactive hyperaemia (flow mediated dilation: FDM) and to
      glyceryltrinitrate (GTNMD) were measured. The IMT was significantly increased in
      the Coa group (by 8%, p < 0.001) and higher in the Coa HT group compared with the
      Coa NT group (0.57 +/- 0.04 mm vs 0.54 +/- 0.05 mm, p < 0.05). The CSD was lower
      and the Einc was higher in both groups. The carotid pulse pressure amplitude was
      significantly higher in the Coa HT Group (41 +/- 14 vs 33 +/- 7 mmHg; p < 0.05).
      The AI was higher in both Coa repair groups. Both flow-mediated dilation (FMD)
      and GTN-mediated dilation (GTNMD) of the brachial artery were lower in the Coa
      group (respectively 5 +/- 3 vs 7 +/- 3%; p < 0.01; 16 +/- 8 vs 23 +/- 9%; p <
      0.01). GTNMD was inversely correlated with maximum systolic blood pressure on
      exercise (r = 0.31, p = 0.03). The IMT of the CCA was related to the local pulse
      pressure in both groups of coarctation repair. The combination of distensibility
      decrease in the proximal arterial bed with an impairment of distal artery
      reactivity would account for the elevation of exercise blood pressure in subjects
      who had coarctation repair. The increase of local pulse pressure influences the
      carotid wall hypertrophy.

PMID- 11575205
TI  - [Left ventricular hypertrophy and sinus variability in arterial hypertension].
AB  - BACKGROUND: Previous studies of heart rate variability (HRV) in systemic
      hypertension have yielded conflicting results. We sought to assess the
      alterations of HRV in hypertensive patients with or without left ventricular
      hypertrophy (LVH). METHODS: 195 hypertensive patients in sinus rhythm, mean age
      53 +/- 11 years, without diabetes mellitus, nor symptomatic coronary disease or
      systolic dysfunction, were prospectively enrolled. Echocardiographic examination
      allowed their subdivision in 3 groups: normal geometry (112), concentric
      remodeling (43) and LVH (40). Time and frequency domain measures of HRV were
      obtained from 24 h Holter ECG recordings in all patients as in 40 control
      subjects. RESULTS: In comparison with control subjects, the 3 hypertensive groups
      presented a significant decrease of SDNN and total frequency power both indexes
      of global HRV; a significant decrease of pNN50 and high frequency power, indexes
      of HRV reflecting parasympathetic tone, and a significant decrease of SDANN and
      low frequency power, indexes reflecting sympathetic modulation of HRV.
      Comparisons among the three hypertensive groups showed that patients with LVH had
      significantly (p < 0.05) lower low frequency power (5.5 +/- 1.0 Ln m2) than
      patients with left ventricular normal geometry (5.9 +/- 0.8 Ln m2) or concentric
      remodeling (5.9 +/- 0.9 Ln m2). CONCLUSION: Assessment of HRV in hypertensive
      patients shows a constant decrease of parasympathetic indexes and a more markedly
      reduction of sympathetic parameters in presence of LVH.

PMID- 11575206
TI  - [Microalbuminuria, pulse wave velocity and common carotid artery intima-media
      thickness in type 2 diabetes].
AB  - The aim of the study was to evaluate pulse wave velocity (PWV) and carotid intima
      media thickness (IMT) in type 2 diabetics with microalbuminuria (mualb). The
      study concerned 37 patients type 2 diabetics, age: 53.4 +/- 6.6, years free of
      cardiovascular complications. HbA1C was 7.73 +/- 1.39%, waist circumference 104.2
      +/- 11.7 cm. 19 patients with BP > 130/85 mmHg were identified as mild
      hypertensives (17/19 under treatment). All patients underwent ABPM, PWV and IMT
      measurements. The study population was separated into 2 subgroups according to
      median of mualb (mg/24 h): 18.9. [table: see text] In patients with mualb > 18.9
      mg/24, IMT and PWV were significantly increased (p = 0.06; p < 0.01). After
      adjustment to BP and age, there was no significant difference in IMT and PWV in
      the subgroups. In this selected population of type 2 diabetics, microalbuminuria
      appears associated to a pressure-dependant vascular remodeling.

PMID- 11575207
TI  - [Role of AT1 receptors in functional adaptation to ischemia-reperfusion in
      solated rat hearts in relationship to oxidative stress].
AB  - Implication of AT1 receptors (AT1R) in functional and metabolic modifications
      associated with ischemia-reperfusion is not clearly defined. The aim of this
      study was:--to evaluate the role of AT1R in isolated rat hearts subjected to a
      reversible ischemia:--to establish possible relationships between functional
      parameters and oxidative stress during reperfusion period. Isolated hearts
      perfused by the Langendorff method underwent 30 min of a global total ischemia
      followed by 30 min of reperfusion. Functional parameters and LDH release were
      recorded under AT1R stimulation by angiotensin II (AII) (10(-7) M) and/or AT1R
      blockade by losartan (10(-6) M). Quantification of oxidative stress was performed
      in coronary effluents 1) directly, using ESR spectroscopy associated with PBN
      spin trapping and 2) indirectly, using HPLC method to detect glutathione (GSH +
      GSSG) release. Our results showed that All induced vasoconstrictive and negative
      inotropic effects during control period. During reperfusion. All reduced
      incidence of reperfusion arrhythmia and LDH release. From the onset of
      reperfusion, a large and long lasting release of alkyl/alkoxyl radicals and
      glutathione was detected and the intensity of the oxidative stress was not
      significantly changed in the groups treated will All and/or losartan. In
      conclusion, no relationship has been clearly demonstrated between the oxidative
      stress intensity and AT1R activation, but these results couldn't exclude the
      contribution of free radical in some myocardial effects of AT1R stimulation such
      as vasoconstriction and negative inotropic effect.

PMID- 11575208
TI  - [Effect of a non-antihypertensive dose of ramipril on the plasma and tissue renin
      angiotensin system in 27 TGR (mRen2) rats].
AB  - It is admitted that low dose of angiotensin converting enzyme (ACE) inhibitors
      allows the regression of left ventricular hypertrophy (HVG) in experimental
      models where plasma renin activity (PRA) is high. The use of low dose of
      ramipril, an ACE inhibitor, make it possible to explore the place of cardiac
      renin-angiotensin system (RAS) in the regression of HVG independently of blood
      pressure (BP). Twenty rats TGR (mRen2) 27, heterozygous male, 10 weeks old were
      treated by daily oral gavage during 6 weeks by 10 micrograms/kg/jour ramipril or
      distilled water and compared to 10 normotensive Sprague Dawley (SD) rats. BP was
      measured. After the period of treatment, plasma, left kidney and the ventricles
      were removed. On each tissue samples and plasma, angiotensinogen (Aogen), the
      renin activity, angiotensins I (Ang I) and II (Ang II) were determined by
      radioimmuno assay and the activity of ACE was measured by fluorimetry. BP does
      not differ between treated and untreated groups during 6 weeks of treatment but
      is significantly higher compared to SD rats. PRA of untreated rats is high (36 +/
      5 ng Ang I/mL/h). However, treatment did not make it possible to decrease HVG.
      In plasma and kidney treatment's effect on SRA is confirmed by the increase in
      renin activity (plasma: 63 +/- 9 vs 36 +/- 5 ng Ang I/mL/h; kidney: 127 +/- 11 vs
      92 +/- 7 micrograms Ang I/g/h) which is accompanied by an increase of Ang I rates
      (plasma: 297 +/- 31 vs 15 +/- 10 fmol/mL; kidney: 241 +/- 37 vs 160 +/- 12
      fmol/g) and of the reduction in Aogen. An inhibition of ACE is perceptible with
      low dose of ramipril in heart (left ventricle: 1.7 +/- 0.1 vs 2.5 +/- 0.3 nmol
      HisLeu/min/mg protein), but it does not appear significant modifications of the
      other elements of the RAS in this tissue. The Ang II cardiac rates are probably
      not solely defined by cardiac ACE activity, other ways of synthesis being
      described. The absence of regression of the HVG in TGR (mRen2) 27 rat with low
      dose of ramipril could be related to the absence of effect on cardiac Ang II
      rates. In addition, the relation between high PRA rates and the effectiveness of
      low dose of ACE inhibitor in the HVG are not confirmed.

PMID- 11575209
TI  - [In contrast to captopril and enalapril, losartan does not increase mortality of
      gerbils after carotid ligation].
AB  - OBJECTIVE: To check wether the deleterious effect of enalaprilat administered
      before unilateral caroid ligation in the gerbil reported by Fernandez et al. (J
      Cardiovasc Pharmacol 1994; 24: 937) is not a molecule specific effect but an
      angiotensin converting enzyme inhibitor class effect. DESIGN AND METHOD: Survival
      rate of gerbils (an animal with incomplete Willis hexagona) was measured after
      unilateral carotid ligation with preadministration (2 hours before by gavage) of
      saline (0.75 ml) (n = 37); losartan (20 mg/kg) (n = 37), enalaparil (10 mg/kg) (n
      = 37); a combination of losartan and enalapril at the same dose (n = 37); and of
      captopril (75 mg/kg) (n = 35). RESULTS: The survival rate of the gerbils 72 hours
      after carotid ligation was 65% in control, 62% in losartan, 30% in enalapril, 32%
      in enalapril + losartan, and 32% in captopril groups. Statistical analysis (log
      rank test) of the Kaplan-Meier survival curves over 72 hours showed no difference
      between losartan and controls nor between the various groups treated with ACEI.
      However survival was significantly lower in the ACEI groups than in the group
      treated by losartan alone (p < 0.02) or controls (p < 0.02). Intraaortic mean
      arterial pressure was measured in 6 controls, 6 animals treated with losartan and
      6 other treated with enalapril. It was comparable in the losartan and enalapril
      treated animals (65 +/- 2 mm Hg vs 64 +/- 2) but significantly lower than in the
      controls (77 +/- 2 mmHg) (p < 0.02). CONCLUSIONS: In contrast to oral
      preadministration of enalapril and captopril that of losartan does not increase
      the mortality of the gerbil after unilateral carotid ligation in spite of the
      same decrease in systemic blood pressure. Although a lower mortality than in
      controls was not observed with losartan as in the princeps study of Fernandez,
      these data are consistent with the demonstration by this author that angiotensin
      II plays a critical protective role in acute ischemia probably by promoting
      collateral circulation recruitment through non-AT1 receptors stimulation.

PMID- 11575210
TI  - [Autoregulation of renal blood flow and blood pressure variability in the
      conscious rat].
AB  - It is often proposed that autoregulatory mechanisms prevent acute changes in
      systemic blood pressure (BP) from being transmitted to the glomerular capillary
      circulation. However, it is not known whether renal blood flow (RBF) is still
      autoregulated when the kidney is exposed to exaggerated BP fluctuations, in
      particular hypertensive episodes. The aim of the present study was therefore to
      evaluate the efficacy of renal autoregulatory responses in an animal model of BP
      lability, the sinoaortic denervated (SAD) rat. BP and RBF were simultaneously
      recorded in 8 SAD (2 wks before study) and 8 baroreceptor intact (INT) Sprague
      Dawley rats during approximately 3 h of spontaneous activity. The left kidney
      used for RBF recordings was denervated to prevent the interference of changes in
      renal sympathetic tone with autoregulatory responses. The SAD procedure modified
      neither the mean BP nor the mean RBF levels (111 +/- 1 mmHg and 11.3 +/- 1.3
      mL/min in INT rats: 113 +/- 6 mmHg and 11.1 +/- 0.9 mL/min in SAD rats). However,
      SAD strongly increased the BP variability (coefficient of variation: 5.9 +/- 0.2%
      and 18.2 +/- 1.1% in INT and SAD rats, respectively). In spite of this marked BP
      lability, RBF variability was not significantly affected by the SAD procedure
      (9.1 +/- 0.8% and 12.4 +/- 1.6% in INT and SAD rats, respectively). In SAD rats,
      spontaneous hypertensive episodes (top 1% of BP values: 174 +/- 10 mmHg) did not
      induce increases in RBF (10.5 +/- 1.0 ml/min). Fast Fourier transform analysis
      revealed that in SAD rats, autoregulatory mechanisms attenuated approximately 80%
      of BP fluctuations in the 0.0015-0.01 Hz frequency range, suggesting a major
      involvement of the tubuloglomerular feedback. In conclusion, autoregulatory
      mechanisms have an ample capacity to protect the kidney against spontaneous BP
      fluctuations in the conscious rat. Consequently, BP variability per se is
      probably not detrimental to the kidney, as long as autoregulatory mechanisms are
      normally functioning.

PMID- 11575211
TI  - [Regional management of arterial hypertension in France. Report of a survey of
      general practitioners].
AB  - A survey was conducted in 14 regional samples of general practitioners (GPs)
      included in Gallup-up poll. 2,423 GPs contributed to the study and had to include
      all patients > 18 years old over a period of one week. Patients were considered
      hypertensives if the mean of two recorded BP measurements was > or = 140/90 mmHg
      and/or < 140/90 mmHg if they were under antihypertensive treatment. Hypertensives
      were considered as controlled if there BP levels were overall < 140/90 mmHg under
      treatment. The risk factors associated with hypertension were collected in order
      to evaluate the cardiovascular risk, according to 1999 ISH-OMS recommendations.
      156,470 patients recruited by 2423 GPs were included in the study representing 14
      different French regions: Ile-de-France I (1), Ile-de-France II (2), Ile-de
      France-Pays-de-la-Loire (3), Bretagne (4), Normandie-Picardie (5), Nord-Pas-de
      Calais (6), Alsace-Lorraine (7), Bourgogne-Franche Comte (8), Rhones-Alpes (9),
      Provence-Cote d'Azur (10), Languedoc-Provence (11), Limousin-Auvergne (12), Midi
      Pyrenees (13), Aquitaine (14). Among 70,073 hypertensives, 23,054 had never
      received antihypertensive treatment, and 32,059 (47%) had a high or a very high
      cardiovascular risk. 67% of hypertensives (47,019) were treated, and 32.8% of
      treated hypertensives (15,422) had a BP < 140/90 mmHg. The study illustrated few
      differences in prevalence and control of hypertension in the different French
      regions: BP control at the 140/90 mmHg threshold vary from 28.5 to 36.6% among
      treated hypertensives and % of patients at high cardiovascular risk from 42.1%
      (South-France) to 49.7% (East-France).

PMID- 11575212
TI  - [Are demographic characteristics of hypertensive patients different with renal
      artery stenosis?].
AB  - Atheromatous renal disease is more and more involved in end stage renal failure
      in polyatheromatous patients. The goal of this work was to study the demographic
      differences between hypertensive patients with renal artery stenosis (RAS) or
      without RAS. METHOD: Between November 1995 and July 1997, 49 hypertensive
      patients were included consecutively for a suspicion of RAS. Age, sex,
      hypertension history, tabagism, cardiovascular heredity, body mass index,
      diabetes history, hypercholesterolemia, kalmia, serum creatinine, creatinine
      clearance, systolic blood pressure (SBP), diastolic blood pressure (DBP) and
      pulse pressure (PP) were studied. A renal echo-doppler and a renal TDM were
      performed in all patients. A renal arteriography was performed in 23 patients
      with a RAS suspicion after the two morphologic exams. The demographic
      characteristics of both clinical groups control (group 1) and patients with
      unilateral RAS (group 2), were compared. STATISTICS: Descriptive analysis,
      Wilcoxon test, Khi 2 test, spearman correlation (p < 0.05). RESULTS: Group 2
      patients were significantly older than group 1 patients (p = 0.008) with a mean
      age difference of 8 years. Creatinine clearance was lower in patients suffering
      from RAS with a mean difference of 23 mL/min between groups 1 and 2 (p = 0.0007)
      but we also had to take into account the negative correlation existing between
      creatinine clearance and age (r = 0.63; p = 0.0001) when interpreting these
      results. The DBP was lower (p = 0.03) and the PP higher (p = 0.01) in group 2.
      The SBP was higher in group 2 but this result was not significant. Mean
      differences in SBP and PP between group 1 and group 2 were 6 mmHg and 15 mm Hg
      respectively. Smoking was more common in group 2 (p = 0.04). The history of
      hypertension, cardiovascular heredity, sex ratio (M/F), body mass index and
      prevalence of diabetic were comparable between the two clinical groups.
      CONCLUSION: Although there were demographic differences between the two clinical
      groups, no clinical or biological variable could be used alone to identify which
      patients suffered from renal stenosis, because the distribution of these
      variables did not differ significantly between the two groups and the effective
      was small. Then, we thought that Krijnen's predictive rule is interesting in the
      screening of hypertensive patients with RAS suspicion.

PMID- 11575213
TI  - [Differences between management guidelines and global health strategies for
      arterial hypertension with metabolic disorders in France in 1999. Ohara study].
AB  - Taking into account all the risk factors and blood pressure levels, as indicated
      by several American and European recommendations available since 1997, is a
      leading strategy to reduce mortality and morbidity of hypertensive patients. The
      aim of this study was to quantify how, in 1999. French practitioners applied
      recommendations on hypertension (HTN), diabetes and hypercholesterolemia in
      recently diagnosed hypertensive patients and to evaluate whether or not the
      recommended targets were met. 1639 French GPs and cardiologists included 5831
      recently diagnosed (7.5 +/- 3.6 months) hypertensives (57 +/- 12 years of age,
      M/F = 55/45%). Initial BP was 173 +/- 15/99 +/- 9 mmHg. 56% had no concomitant
      disease, 36% had either diabetes, dyslipidemia or coronary heart disease, 8% had
      at least two concomitant diseases. At the time of the study corresponding to 6.3
      +/- 3.8 months after initiation of diet and/or medical treatment, their BP was
      148 +/- 17/86 +/- 11 mmHg (-25/-19 mmHg). At that time only 37% of patients with
      stage 2 HTN were encouraged to adopt lifestyle modifications without any medical
      treatment as recommended by the JNC VI. Among these hypertensives, measurement of
      plasma cholesterol was performed in only 61%, HDL-C/LDL-C in 26% and blood
      glucose in 51%. In the patients with dyslipidemia, LDL-C was measured in only
      47%. In the 677 diabetic patients only 27% had a glycated hemoglobin measurement.
      The percentage of patients reaching target BP was 59% as regard DBP < 90 mmHg,
      25% as regard SBP < 140 mmHg, and 23% reached both target values of BP. In
      addition, 30% of patients with dyslipidemia reached the target LDL-C as defined
      by French recommendations (ANAES 1996) and 30% of the diabetic patients reached
      the target value for glycemia recommended by ADA (1997). In 1999 in France, a
      minority of patients reaches the national or international recommended target
      values for blood pressure, glycemia and plasma LDL-cholesterol. In spite of that,
      French practitioners do not implement all the available diagnostic tools to
      improve the treatment of metabolic disorders in hypertensive patients. As a
      conclusion, to improve the prognosis of hypertensive patients, it is mandatory to
      raise the awareness of physicians about multiple risk factor management and help
      them implement the recommendations in their daily practice.

PMID- 11575214
TI  - [Evaluation of patient compliance among hypertensive patients treated by
      specialists].
AB  - OBJECTIVES: To evaluate compliance with antihypertensive therapy by a self-report
      in patients referred to hypertension specialists. METHODS: We studied 484 treated
      hypertensive subjects referred to several hypertension clinics and who were
      treated since at least one year. Patients were asked to fill in the Compliance
      Evaluation Test (CET), a questionnaire with 6 questions previously validated to
      assess factors that could affect medication compliance. We defined patients as
      "good compliant" when "No" was answered to the 6 items, as "minor noncompliant"
      when 1 or 2 "Yes" were answered, and as "noncompliant" when 3 or more "Yes" were
      answered. A good agreement was demonstrated between CET score and compliance
      evaluated by the number of pills missed during the previous month according to
      patient interview. RESULTS: We observed 8% of "noncompliant", 53% of "minor
      noncompliant" and 39% of "good compliant". [table: see text] Logistic regression
      analysis including age, sex, education level, blood pressure level and the number
      of antihypertensive tablets confirm the statistical differences observed.
      CONCLUSIONS: In clinical practice, a method of assessing medication compliance is
      to ask the patient for a self-report interview. We demonstrated that the
      compliance evaluation test is able to detect factors usually associated with poor
      compliance (young age, elevated blood pressure, number of tablets per day). The
      use of the compliance evaluation test may help physicians to face the problem of
      nonadherence among their hypertensive patients.

PMID- 11575215
TI  - [Arterial hypertension management in general practice in France according to
      global risk factors].
AB  - OBJECTIVE: The absolute benefit of antihypertensive medications increases with
      the level of cardiovascular risk. Moreover in high risk groups, it has been
      demonstrated that tight blood pressure (BP) control conferred a substantial
      reduction in the risk of cardiovascular events compared to less tight BP control.
      Taking into accounts these data, the WHO guidelines recommend to achieve normal
      BP in high risk subjects. The aim of the study was to assess BP control in a
      large population of hypertensives (HT) after stratification by cardiovascular
      risk. METHODS: 15,514 HT defined as office BP > or = 140/90 or the presence of
      antihypertensive treatment were recruited in France by 3,152 general
      practitioners. Cardiovascular risk factors and office BP were recorded.
      Controlled hypertension was defined as a BP < 140/90 mmHg. In patients free of
      cardiovascular disease, 10-year cardiovascular risks were calculated on the basis
      of the equations derived from the Framingham Study. RESULTS: 10-year risks were
      available in 13,560 HT. Those in the highest quartile had greater body mass index
      (BMI) and the highest concentration of diabetics and current smokers (upper
      quartile versus lower quartile: BMI: 28.15 vs 26.51 kg/m2; diabetics: 45% vs 3%;
      current smoking 32% vs 12%; p < .001). [table: see text] Increasing quartiles of
      risk were associated with the prevalence of uncontrolled hypertension and at a
      lesser extent with the use of combination therapy. Subjects in the upper quartile
      had more frequent calcium-blockers, ACE inhibitors and diuretics use and a less
      frequent betablocker use. CONCLUSION: In general practice, 85% of hypertensives
      at highest risk are uncontrolled whereas half of them are under monotherapy. An
      antihypertensive strategy based on global risk may improve BP control in high
      risk patients.

PMID- 11575216
TI  - [Influence of cardiovascular risk factors on prescribing of antihypertensives].
AB  - OBJECTIVE: The World Health Organization Guidelines on the management of
      Hypertension recommends to take care of cardiovascular risk factors for selecting
      drug treatment. The aim of the study was to analyze relationship between
      cardiovascular risk factors and use of antihypertensive drugs in general practice
      in France. METHODS: This was a national cross sectional epidemiological survey
      performed by 3,152 general practitioners between September 1999 and May 2000.
      Each investigator had to include 5 consecutive hypertensives (HT) (BP > or =
      140/90 or presence of antihypertensive treatment). Cardiovascular risk factors,
      antihypertensive treatments and office BP were recorded. A stepwise logistic
      regression analysis was performed for each class of antihypertensive treatment in
      order to determine risk factors associated with prescription. Significant
      threshold was fixed at 0.05. Results are expressed in the form of odds ratios
      (OR). RESULTS: 14,551 treated hypertensives (mean age 60 +/- 10 years, male 56%)
      were analyzed. Sixteen per cent of patients were diabetics, 17% current smokers
      and the mean value of cholesterol was 2.29 +/- 0.37 g/L. ACE inhibitors,
      diuretics, beta-blockers (BB), dihydropyridines, angiotensin II antagonists
      (AAII), non DHP calcium antagonists (CA) were prescribed in respectively 47%,
      35%, 28%, 18%, 14% and 12% of patients. The main risk factors associated with
      each kind of prescription was diabetes for ACE (OR = 1.36), coronary artery
      disease for BB, DHP and non-DHP CA (OR = 2.53; 1.51; 1.4 respectively) and BMI
      for AAII (OR = 1.03). OR > 1 indicates that risk factors was positively linked to
      prescription. Age had minor influence on selecting drug treatment. Conversely to
      BB and AAII, the use of ACE and non-DHP CA increases with presence of diabetes
      and cholesterol increase. CONCLUSION: In general practice, presence of
      cardiovascular risk factors influences mildly management of hypertension.
      Conversely to BB, ACE are more prescribed in HT with metabolic disorders.

PMID- 11575217
TI  - [APOC3, CETP, beta-fibrinogen and MTHFR are genetic determinants of carotid intim
      media thickness (Stanislas cohort)].
AB  - The purpose of this study was to examine the relationship between carotid intima
      media thickness (CIMT) interindividual variability and 16 polymorphisms of 11
      genes associated with cardiovascular risk factors (genes among lipid and
      homocysteine metabolisms, blood viscosity, platelet aggregation, leukocyte
      adhesion and renin-angiotensin system). CIMT was measured by high resolution B
      mode ultrasonography in an healthy population of 77 men and 84 women, aged 35-54
      years and selected from a French cohort: the Stanislas cohort. The polymorphisms
      studied were genotyped by a multilocus approach. Statistical analysis were done
      by ANOVA after adjustment of CIMT for age, BMI and smoking and by multiple
      regression analyses. No association was found with APOB Thr71 Ile, APOC3 -482C/T,
      -455T/C, GpIIIa P1A, AT1R 1166A/C, AGT Met235Thr, CBS Ile278Thr, SELE 98G/T and
      SELE Ser128Arg, polymorphism neither in men nor in women. Although, in women we
      found always no association for the APOC3 3206T/G, 3175C/G, 1100C/T, the CETP
      Ile405Val, the MTHFR 677C/T and the fibrinogen -455G/A polymorphism's, in men
      these polymorphism's were associated with CIMT variability (0.01 < or = p < or =
      0.05). The most interesting finding was that altogether these genes in men were
      able to explain a considerable part, 20.6%, of CIMT variability. Therefore, our
      study gives a new opportunity to understand CIMT variability.

PMID- 11575218
TI  - [Association between E-selectin Leu554Phe polymorphism and blood pressure in the
      Stanislas cohort].
AB  - We investigated the relationship between polymorphisms of the E-selectin gene,
      SELE (L/F554, S/R128 and 98G/T), a cell adhesion molecule, and interindividual
      variability in blood pressure and changes over time. The study population was
      extracted from the Stanislas Cohort (1006 families), a cohort of nuclear families
      volunteering for a free health check-up and recruited by the Centre of Preventive
      Medicine in Nancy (CMP) between 1993 and 1994. For this specific study, 359 men
      and 337 women were selected from families that had already visited the CMP 11
      years before the recruitment of the Stanislas Cohort. Measurements of blood
      pressure at the time -11 years (t-11) and at the time of recruitment (t0), and
      all other measurements necessary for the analysis (BMI, lipids, SELE genotypes)
      were available. Pregnant women or subjects taking antihypertensive, lipid
      lowering or anti-inflammatory medications were excluded from the study. During
      the follow-up period, systolic and diastolic blood pressure (SBP and DBP) were
      lower in SELE F554 allele carriers than in those with the L/L554 genotype (p < or
      = 0.05), whereas longitudinal changes were not related to any SELE polymorphism.
      Multiple regression analysis showed that at t-11 SELE L/F554 polymorphism was
      associated with both SBP and DBP levels (p < or = 0.01 and p < or = 0.05,
      respectively). However, these associations were no longer present at t0. Our
      results suggest an age-specific effect of the SELE L/F554 polymorphism on blood
      pressure levels. If confirmed in other studies, these findings would suggest that
      assessment of common variation in an adhesion molecule could be useful in
      predicting blood pressure.

PMID- 11575219
TI  - [Blood pressure control after acute coronary events. Results of the PREVENIR
      study].
AB  - OBJECTIVE: The difficulty in controlling hypertension in coronary patients has
      been underlined. The aim of the study was to assess blood pressure profile (BP)
      at hospital discharge in a large population of survivors of an acute coronary
      syndrome. DESIGN AND METHODS: An observational study was conducted in France in
      77 cardiological centers. The medical records of all patients admitted in these
      hospitals on January 1998 for a myocardial infarction or unstable angina and who
      survived were studied. Clinical characteristics and BP at hospital discharge were
      recorded. Patients with blood pressure > or = 140/90 mmHg were considered as
      uncontrolled hypertensives (HT). RESULTS: Data were available in 1327 of the 1394
      patients recruited: at hospital discharge, 344 patients (25.9%) were controlled
      and 431 (32.4%) were uncontrolled hypertensives. Among these patients, 406
      (94.1%) had systolic blood pressure > or = 140 mmHg, 139 (32.2%) had diastolic
      blood pressure > or = 90 mmHg and 292 patients (67.7%) had systolic blood
      pressure > or = 140 mmHg and diastolic blood pressure < 90 mmHg. Pulse pressure
      in controlled hypertensives (51.02 +/- 10.93 mmHg) was quite similar to that in
      normotensives (47.81 +/- 9.84 mmHg) whereas pulse pressure was significantly
      higher in uncontrolled hypertensives (65.86 +/- 13.29 mmHg). CONCLUSION: At
      hospital discharge after a coronary event, arterial hypertension is uncontrolled
      in 32.4% of patients mainly because of poor systolic blood pressure control.
      Achieving normal blood pressure throughout the hospitalisation should improve
      long term blood pressure control, reduce pulse pressure and improve the prognosis
      in this high risk population.

PMID- 11575220
TI  - [Study of blood pressure, hemodynamic, ventilatory and metabolic responses to
      isometric exercise performed during dynamic exercise in health subjects].
AB  - The object of this study was to study the blood pressure, haemodynamic,
      ventilatory and metabolic changes on isometric exercise during a dynamic effort
      in healthy subjects. Twelve healthy subjects underwent isometric exercise by
      manual prehension at 40% maximal capacity under these conditions: isolated (A),
      five minutes after the onset of rectangular dynamic exercise on a cycle at 60% of
      ventilatory threshold (B) and at the fourth minute of the recovery phase of
      dynamic exercise (C). The blood pressure, heart rate, stroke volume and cardiac
      index measured by Doppler echocardiography, systemic arterial resistances,
      respiratory flow and respiratory rate, were measured before and after each
      isometric exercise. The results showed blood pressure and heart rate to increase
      in a similar manner during isometric exercise under all conditions. The cardiac
      index increased by 29.5% +/- 8.3% (p < 0.01) under condition A and by 38.1% +/-
      10% (p < 0.01) under conditions C but did not change significantly under
      conditions B. On the other hand, the systemic arterial resistances increased by
      15.5% +/- 6.5% (p < 0.05) under conditions B, decreased by 8.8% +/- 3.9% (p <
      0.05) under conditions C but did not change significantly under conditions A. The
      respiratory flow increased under all three conditions although the respiratory
      rate was only increased under conditions B. The authors conclude that, in healthy
      subjects, the increase in blood pressure during isometric and dynamic exercise is
      the result of an increase in systemic resistances whereas, during isometric
      exercise, it is flow-dependant.

PMID- 11575221
TI  - [Aterial hypertension and cardiovascular risk factors associated with diabetes.
      Report of the PHARE survey in general practice].
AB  - OBJECTIVE: To evaluate the characteristics of diabetic hypertensive patients
      (Pts), in term of associated cardiovascular risk factors and blood pressure
      control in a representative population issued from a survey "PHARE" conducted in
      general practice in France in 1999. DESIGN AND METHODS: PHARE survey was
      conducted in a sample of 225 GPs representative of the French medical population
      included in a gallup poll. GPs had to include all patients > 18 years old over a
      period of one week. Pts were considered as hypertensives (HP) if the mean of two
      recorded BP measurements was = 140/90 mmHg and/or < 140/90 mmHg if they were
      under antihypertensive treatment. Patients were considered as diabetics if they
      were previously known and/or if they received a medication for diabetes.
      Hypertensives were considered as controlled if their BP levels were overall <
      140/90 mmHg or at the recommended threshold < 130/85 mmHg under treatment.
      RESULTS: 877 diabetic Pts (7%) among 12.342 Pts and 5.190 HP were included in the
      study. When compared to normotensives, diabetic HP had more frequently associated
      risk factors with hypertension and diabetes: overweight 71% vs 45%, dyslipidemia
      61% vs 34%, sendentarily 73% vs 63%, tobacco consumption 27% vs 20%. The BP
      control at 140/90 mmHg threshold among treated diabetic HP was 21%, and only 8%
      at 130/85 mmHg. Regarding WHO classification, 79% of these diabetics had a high
      or very high cardiovascular risk. The were no difference in antihypertensive
      drugs used in HP diabetics and non diabetics and 50% of them received ACEI.
      CONCLUSIONS: 8 from 10 diabetics taken in charge in general practice are
      hypertensives and 8 from 10 have a very high cardiovascular risk due to a poor BP
      control and associated cardiovascular risk factors.

PMID- 11575222
TI  - [Adrenal vein catheterization in primary hyperaldosteronism: aid in surgical
      decision making?].
AB  - The localisation of aldosterone-producing adenomas (APA's) remains difficult.
      Indeed, CT scan may not detect small APA's while CT detected tumours do not
      necessarily produce aldosterone. OBJECTIVE: To evaluate the value of adrenal vein
      catheterization (AVC) for the diagnosis of APA's and also the rates of
      unsuccessful procedures and complications. PATIENTS: One-hundred-and-nine
      hypertensives with biological features of primary hyperaldosteronism were
      included. Plasma sodium, potassium, aldosterone and renin levels were obtained
      after one night in lying position. Aldosterone and renin levels were also
      measured after a one-hour walking period and after a sodium expansion with
      saline. All patients underwent a CT scan and AVC. For adrenal samples, the ratio
      of aldosterone to cortisol concentrations was calculated for both sides. Both
      ratios were divided by the opposite one and the higher was retained as an index
      of laterization (IL). For lack of a golden standard variable, we have taken as a
      working hypothesis that operated patients had an APA (n = 38) and the non
      operated ones bilateral hypereplasia (n = 71). RESULTS: Operated patients had a
      shorter history of hypertension, more frequently a left ventricular hypertrophy
      on ECG, and lower serum creatinine and potassium levels, along with a higher
      sodium level. None of these features appeared discriminant, however. Presence of
      a 10-mm tumour on CT scan was not significantly different between the 2 groups.
      Operated patients had more than a five-fold higher IL compared with that of non
      operated patients. Analysis using a ROC curve showed that the value of 12 for
      "IL" was an acceptable operational criterium of lateralization, producing a
      specificity of 90%, while maintaining a sensitivity of 62%. AVC appeared most
      useful in case of middle-range pre-test probability of an APA being present, that
      is when when clinical, biological, or radiological features are not fully
      concordant. The rate of unsuccessful procedure and the rate of complications were
      low (1.8% and 3.6%, respectively). CONCLUSION: With a low iatrogenicity, AVC
      appears helpful in indicating surgery mostly when clinical, biological, and CT
      scan features are not fully concordant. A value of 12 for IL appears to allow a
      high specificity while retaining an acceptable sensitivity.

PMID- 11575223
TI  - [Blood pressure self-monitoring contributes to improved patient education among
      hypertensive subjects].
AB  - Education of hypertensive subject must sensitize the patient to its pathway and
      to the prescribed treatment. Self-measurement of blood pressure, which directly
      implicates the patient, should ameliorate the education of hypertensive subject.
      OBJECTIVES: To evaluate if the possession of a self-measurement blood pressure
      device improves patients' knowledge of hypertension. METHODS: In 484 treated
      hypertensive subjects referred to hypertension specialists, a questionnaire
      evaluating patients knowledge of hypertension and its treatment was given before
      the consultation. During this consultation, the practitioner evaluated the
      concordance between antihypertensive treatments declared by the patient and those
      effectively prescribed. RESULTS: In this population, aged 61 +/- 12 years, with
      55% of men, a self-measurement blood pressure device was possessed by 165
      subjects (34%). These devices have been bought without medical advice by 83
      patients. For a minority of subjects (n = 41), self-measurements of blood
      pressure were made at the wrist. Blood pressure level was similar in subjects
      with (141 +/- 19/80 +/- 10 mmHg) or without (140 +/- 19/80 +/- 10 mmHg) self
      measurement devices. Subjects possessing a self measurement device had a better
      knowledge of their usual blood pressure level and of the normal blood pressure
      values (< 140/90 mmHg), than subjects without self measurement device (93% vs
      77%, p < 0.01, and 56% vs 33%, p < 0.01, respectively). Moreover, subjects in
      possession of self-measurement devices had a better knowledge of their
      antihypertensive treatment than those without device (83% vs 70%, p < 0.05).
      Logistic regression analysis including age, sex, smoking, education level, blood
      pressure level and the number of antihypertensive tablets confirm the statistical
      differences observed. CONCLUSION: Hypertensive subjects who possess a self
      measurement blood pressure device have a better knowledge of their hypertension.
      These results indicate that the possession of a self-measurement device
      contributes to the education of hypertensive patients.

PMID- 11575224
TI  - [Quality of blood pressure measurement in the management of arterial
      hypertension. Pilot study].
AB  - In clinical practice, diagnosis and follow-up of hypertension is based on blood
      pressure (BP) as measured by auscultatory method. BP is usually measured using a
      stethoscope to auscultate the Korotkoff sounds and mercury or an aneroid
      sphygmomanometer. However due to the lack of regulatory rules, the devices are
      rarely checked making the quality of the measures doubtful. OBJECTIVE: To compare
      BP measured following the WHO recommendations, using 2 different devices: the
      mercury or aneroid sphygmomanometer used by the physician and a SECURUS manometer
      that has been calibrated just before the implementation of the study. METHOD: The
      study was performed with 1694 French general practitioners. Every physician
      included 2 ambulatory patients: a newly diagnosed non-treated hypertensive
      patient and a treated hypertensive patient. The physician was asked to include
      the first patient of each category attending his office. BP was measured
      sequentially with the 2 devices in a random order. Collected data were socio
      demographic parameters, cardiovascular risk factors, hypertension related
      diseases, drug treatment for hypertension and BP levels. RESULTS: Mean BPs differ
      by less than 1 mmHg between the 2 devices. However 10% of the treated
      hypertensive patients are not classified as having normalised BP values (BP <
      140/90 mmHg) or high BP values, in the same way by the 2 devices. Mean absolute
      difference between the 2 devices is > 5 mmHg in 22% and 13% of the physicians for
      SBP and DBP respectively. CONCLUSION: This pilot study emphasises the need of BP
      measurements of good quality in clinical practice, because of the possible impact
      on the care of the patients and the related costs. Regulatory rules on the
      control of the devices might improve the quality of BP measurements.

PMID- 11575225
TI  - [Evaluation of blood pressure control by repeated ambulatory automatic blood
      pressure measurements].
AB  - The aim of this study was to compare the evaluation of blood pressure control in
      using an automatic blood pressure device (ABPD) and an ambulatory blood pressure
      measurement (ABPM). METHOD: 41 patients with essential hypertension (HTA) were
      screened prospectively from April to June 2000 (22 men and 19 female) mean age 63
      years old, 2.6 antihypertensive drug per patient). The blood pressure was
      randomly measure by 2 physicians with an automatic blood pressure device OMRON
      705 CP, 3 times. All the patients had a 24 hours ABPM in the month before and
      after this measure, without change in medication. RESULTS: The mean blood
      pressure measured was 151/81 mmHg by the first physician, 149/85 mmHg with the
      physician observer and 131/81 mmHg with the ABPM. The percentage of patient who
      have an optimal control was significantly less in the ABPD estimation (27% <
      140/90 mmHg) than ABPM (Day ABPM < 135/85 mmHg = 51%). In conclusion, the control
      of hypertension still remains insufficiency even if the utilisation of ABPM may
      increase the accuracy of that estimation.

PMID- 11575226
TI  - [Influence of protocol on the quality of blood pressure self-monitoring].
AB  - OBJECTIVES: To determine the minimum number of self-measurements of blood
      pressure to provide the maximum quality and reliability during home-blood
      pressure monitoring. METHODS: We studied 38 hypertensive subjects in which we
      compared self-reported with electronically stored home BP (OMRON HEM 720 CIC).
      Subjects were asked to measure BP in the sitting position, three times
      consecutively in the morning and three times in the evening during 7 consecutive
      days. BP values over the 7 days were averaged and the differences with BP
      recorded over the first day (6 values per day), the first 2 days, the first 3
      days, the first 4 days, the first 5 days and the first 6 days were calculated.
      Confidence interval were calculated. RESULTS: We observed that 47% of patients
      completed the entire protocol (42 measurements over 7 days), but 89% completed 4
      days with 6 measurements. Erroneous reporting was evident in 10% of patients. In
      patients which performed 100% of the 42 planned values, confidence interval for
      the mean value was < 4 mmHg for SBP and < 3 mmHg for DBP when the patient
      completed a 4 days protocol with a minimum of 4 measurements per day.
      CONCLUSIONS: These results indicate that determining average home blood pressure
      over 4 consecutive days with 2 measurements twice daily, is the minimum protocol
      that provides a reliable estimate of home blood pressure with a good quality of
      patient reporting.

PMID- 11575227
TI  - [The REVEIL study: feasibility study of blood pressure self-monitoring.
      Preliminary results and patient opinions].
AB  - The REVEIL study is a pilot studies to determine the feasibility of self blood
      pressure measurement (SBPM). Feasibility was assessed by the quality of
      measurements and the patient opinion. This preliminary report focused on the
      patient opinion. Patients were included in the study by their general
      practitioner or cardiologist when he thought there was an indication for SBPM.
      Patients were excluded if their physical or mental autonomy was not sufficient to
      perform SBPM or if they were arrhythmic. The lending of the device was free
      (against a guarantee of 800 F) and it was available in one of the 44 drugstores
      that participated to the study. The physician performed patient education about
      SBPM and the druggist explained the handling of the device. SBPM was performed
      over a 7-day period: every day two series of 3 consecutive measurements were
      requested in the morning before taking the antihypertensive treatment, and in the
      evening between dinner and bedtime. The device was the validated OMRON 705 CP.
      428 patients were included in the study. Among them, 385 (90%) accepted to
      participate to the study and 43 refused (10%). Almost half of the refusals were
      due to patients that did not want to take care of them and 16% were justified by
      a technical problem. Preliminary data included 362 patients aged 55.2 years, 79
      of them older than 70 years. 80 patients (22%) experienced difficulties to
      perform SBPM, 28 of them (7.3%) to perform measurements and 13 (3.4%) to
      understand how worked the device. At the end of the study, 82 patients (23%) had
      better understanding of their hypertension, 90 patients (25%) felt themselves
      more motivated to take their medication and 111 patients (31%) found that their
      physician took better charge of them. 286 patients (79%) evaluated the overall
      satisfaction at SBPM. Among them, 276 patients (97%) were very satisfied (57%) or
      satisfied (40%) with SBPM when only 3% of patients were not. In summary, SBPM was
      easily performed in the conditions of the REVEIL study, and the majority of
      patients was satisfied with this experience.

PMID- 11575228
TI  - [REVEIL Trial: Study validity, information and logistics. Preliminary results.
      Quality measures].
AB  - Self blood pressure measurement (SBPM) is not fully applied because of the cost
      of devices and the lack of efficient dedicated medical networks. The aim of the
      REVEIL study was to allow patients to freely rent SBPM devices by their
      pharmacist after initial medical prescription. Practitioners taught SBPM methods
      to the patients with a booklet and the pharmacist explained them how to use the
      device. This preliminary report focuses on the 428 first patients included from
      September 1999 to June 2000 by their general practitioner (n = 59) or
      cardiologist (n = 12) in the centre of the city of Reims (France), when he
      thought there was an indication for a SBPM period. The patient received a medical
      prescription and took a validated device (Omron 705CP) by one of the 44
      pharmacists who accepted to participate. After 7 days the patient consulted his
      practitioner with the filled booklet. The prescription was for 7 days with 3
      measurements each morning (before intake of antihypertensive drugs) and each
      evening (12 hours later). Patients reported the results on the booklet and
      enclosed the report printed by the device. From the 428 included patients, 362
      (85%) gave analyzable data, the difference being explained by refusals (n = 39)
      and by the lag between inclusion and completion. Mean age was 55.2 (range 20 to
      90). Education levels were: no graduation (n = 71), primary school (n = 172),
      college (n = 59), university (n = 86) [no answer in n = 40]. Seventy nine percent
      (n = 286) performed at least 12 measurements on three consecutive days. There is
      no significant difference between morning and evening completions. According to
      themselves, 294 patients fully succeeded in SBPM. Eighteen failed (6 reported a
      failure of the device, 2 had not understood the procedure, 5 had forgotten, 5
      reported another cause), 50 did not answer. These results establish the fair
      applicability of SBPM under the realistic conditions of the REVEIL study (free
      rent of devices after medical prescription) as 85% of patients gave contributive
      information with a good quality in 79% of them.

PMID- 11575229
TI  - [Antihypertensive effect of valsartan 80 mg and hydrochlorothiazide 12.5 mg
      evaluated by ambulatory blood pressure monitoring].
AB  - OBJECTIVE: The aim of the study was to evaluate by ambulatory blood pressure
      measurement (ABPM) the 24 hours antihypertensive efficacy of the fixed
      combination therapy, valsartan 80 mg + hydrochlorothiazide 12.5 mg (V + H), once
      daily, after 6 weeks of treatment, in patients with mild to moderate
      hypertension. STUDY DESIGN: It was a French, multicenter, double blind,
      randomized trial in parallel groups comparing V + H and placebo. After an initial
      two weeks placebo period, patients were assigned to receive either V + H or
      placebo for six weeks. Were eligible those with clinical arterial blood pressure,
      measured by sphygmomanometer, between 160/95 and 209/114 mmHg after monotherapy.
      A 26 hours ABPM, with Spacelabs 90,207, was done at J0 and J42 (one measurement
      every 15 minutes, in day time and at night). Responders were defined as a fall in
      day diastolic blood pressure > or = 5 mmHg and/or day diastolic blood pressure <
      90 mmHg with ABPM. RESULTS: 123 of the 138 randomized patients had two
      interpretative measurements. Their average age was 59 + 10 years. 57% (78) of
      them were males and their average ABPM before treatment was 143 +/- 15/88 +/- 11
      mmHg. With V + H, the reduction of the systolic and the diastolic blood pressure
      measured by ABPM, was significantly more important than with placebo (SBP: -15.4
      +/- 10.9 mmHg versus -0.6 +/- 7.7 mmHg, p < 0.001; DBP: -9.1 +/- 7 mmHg versus 
      0.4 +/- 5.4 mmHg, p < 0.001). Pulse pressure (PP) was also significantly reduced
      with the combination therapy V + H, but it was not modified with placebo (-6.3 +
      5.5 mmHg versus -0.2 + 4.1 mmHg, p < 0.001). ABPM responder rate was 73% with V +
      H versus 24% with placebo (p < 0.001). Trough/peak ratio was 80.3% for systolic
      blood pressure and 57.3% for diastolic blood pressure. The combination V + H was
      as well tolerated as placebo. CONCLUSION: The fixed combination V + H used for
      treatment of hypertension, after failure of monotherapy, is very effective in
      reducing pulse pressure, systolic and diastolic blood pressure, over 24 hours,
      homogeneously, and is as well tolerated as placebo.

PMID- 11575230
TI  - [Effect of acupuncture on radial artery hemodynamics. Two controlled studies in
      pre-exposed and naive healthy subjects].
AB  - Palpation of the radial pulses is one of the most important techniques in
      traditional Chinese medicine. Two double-blind randomised trials of the effects
      of real and sham acupuncture on radial artery hemodynamics were conducted in 19
      patients regularly exposed to acupuncture (sensitised subjects), and in 8 healthy
      subjects devoid of previous exposure (naive subjects), respectively. Radial
      artery diameter and pulse waveform was measured with a high-resolution
      echotracking system and aplanation tonometry, respectively, before and during a
      20-minute's acupuncture period. In sensitised patients, arterial diameter
      significantly increased during real acupuncture, compared to the sham group (+7.5
      +/- 2.8% vs -2.9 +/- 2.7%, respectively; p < 0.01). By contrast, in naive
      subjects, arterial diameter did not change during real or sham acupuncture. In
      both populations, no significant difference was observed between real and sham
      acupuncture, concerning the time-course of blood pressure, radial artery
      distensibility and pressure waveform. Our results demonstrate that real
      acupuncture can determine an objective vasodilatation of the radial artery in
      patients regularly exposed to acupuncture, but not in naive subjects.

PMID- 11575231
TI  - [Method of studying renal morphology in hypertensive patients with and without
      renal artery stenosis].
AB  - Although the size of the kidney is still the most commonly used as morphological
      parameter, it is not enough sensitive for early detection of ischemic
      nephropathy. PURPOSE: To study a novel method of renal morphology analysis using
      spiral computed tomography angiography (CTA) in hypertensive patients with or
      without unilateral atheromatous renal artery stenosis (RAS). METHODS: Forty-nine
      hypertensive patients suspected RAS underwent spiral CTA. Arteriography showed
      significant RAS in 26 patients. Renal length, 3 upper and 3 lower cortical
      thicknesses were measured in 46 control kidneys (C) i.e. 23 patients without RAS
      (group 1), in 26 stenosed (S) and in 26 opposite kidneys (OPP) i.e. 26 patients
      with unilateral RAS (group 2). Mean cortical thickness (MCT), cortical area (CA),
      medullary length (ML) were calculated in the same groups. The reproducibility and
      agreement of measurements were investigated in two groups. The demographic
      parameters (age, sex, bodymass index, and history of hypertension) were
      correlated with morphological parameters in group 1. RESULTS: The reproducibility
      and agreement of measurements were confirmed (R2 = 0.53 to 0.93) except for
      anterosuperior thickness. The C kidneys were of comparable morphology: MCT (mm) =
      9.1 +/- 0.6; 9.2 +/- 1.0, CA (mm2) = 950 +/- 119; 934 +/- 157, ML (mm) = 85 +/-
      11. In group of Opp kidneys, MCT = 7.9 +/- 1.4 mm, CA = 806 +/- 210 mm2, ML = 84
      +/- 13 mm. In group of S kidneys, MCT = 6.6 +/- 1.6 mm, CA = 612 +/- 193 mm2, ML
      = 77 +/- 14 mm. Demographic parameters were not correlated to renal morphology.
      CONCLUSION: Spiral CTA is a suitable method to study renal morphology. Cortical
      thickness and medullary length could be used to obtain a reliable diagnosis of
      early ischemic nephropathy.

PMID- 11575232
TI  - [Smoking and atheromatous stenosis of the renal arteries].
AB  - Renal vascular pathologies are important causes of the chronic renal failure
      progression. In these pathologies, the role of smoking in so far as factor of
      risk was discussed. This work aims to evaluate the effect of smoking exposure on
      renal arteries of patients with both renal failure and hypertension. 67 patients
      more than 50 years old, having both renal failure and hypertension, have been
      explored by arteriography. The active smoking was required among all patients.
      Patients were classified in 2 groups: group (I) of 45 patients with one or more
      atheromatous stenoses of renal arteries considered to be significant and group
      (II) of 22 patients without significant atheromatous stenoses of renal arteries.
      [table: see text] 80.5% of patients of group (I) have smoked against only 44.4%
      in group (II). The fact that the presence of atheromatous stenoses of renal
      arteries was connected to the number of cigarettes and the exposure time, and not
      to the current comportment of patients towards smoking, this suggested a
      cumulative effect of smoking. CONCLUSION: This work shown a relation between the
      consumption of smoking and the existence of atheromatous stenoses of renal
      arteries, a reason moreover to fight against smoking. The prevention of smoking
      intoxication appears important to decrease the incidence of the renal vascular
      pathologies.

PMID- 11575233
TI  - [Prospective follow-up study of renal function in type 2 diabetes].
AB  - Type 2 diabetes mellitus is the main cause of increase in patients suffering from
      end-stage renal failure in France. We performed an observational study of the
      change in renal function of type 2 diabetic patients, attending our diabetology
      clinic. Clinical and biological data were regularly entered in an informatic
      database (Penelope, Poitiers University Hospital). We prospectively followed 351
      type 2 diabetic patients (age at diagnosis: 40 to 75 years), for 32 months
      (extremes: 1-120). Renal function was graded in 4 stages according to plasma
      creatinine and urinary albumin excretion (UAE) determined by nephelometry on
      random urinary sample: absent (UAE < 20 mg/L et creatinine < 150 mumol/L),
      incipiens (UAE 20 to 200 mg/L and creatinine < 150 mumol/L), established (UAE =
      200 mg/L et creatinine < 150 mumol/L) advanced (creatinine = 150 mumol/L).
      Glycated haemoglobin (HbA1c) was determined by HPLC. Systolic/Diastolic Blood
      Pressure (SBP/DBP) was measured with a mercury sphygmomanometer. We defined renal
      events as the change from one stage of nephropathy to a higher one. A total of
      351 type 2 diabetic subjects were studied: 194 men/157 women mean age 63 +/- 11
      years, mean diabetes duration 10 +/- 9 yr. At baseline, 206 patients had no
      nephropathy, 98 incipient nephropathy, 28 established nephropathy and 19-advanced
      nephropathy. Baseline stage of nephropathy was related to SBP (p < 0.0001), DBP
      (p = 0.0002), diabetes duration (p = 0.0064) but not HbA1c (p = 0.2182) or sex (p
      = 0.4794). Among those 332 subjects without baseline advanced nephropathy, 134
      progressed in nephropathy. Progression of nephropathy was not related to the
      presence of hypertension (SBP/DBP > or = 160/95 mmHg) (log-rank = 0.22; p =
      0.6377). Conversely, patients with a poor glycaemic control (HbA1c > or = 10%)
      had a worse renal-event free survival (log-rank = 4.89; p = 0.0269). Glycaemic
      control is a risk factor for the progression in nephropathy of type 2 diabetic
      patients.

PMID- 11575234
TI  - [Microalbuminuria in hypertensive, non-proteinuric renal transplant recipients:
      role of previous acute rejection episodes and sodium intake].
AB  - Microalbuminuria (Malb: albuminuria: 30-299 mg/24 h) is associated with many
      cardiovascular parameters (high systolic (SAP) and diastolic (DAP) arterial
      pressure, total cholesterol, triglycerides, fasting glucose and body weight, low
      HDL-cholesterol) and may be a marker of cardiovascular and renal risk in the
      general population. Whether MAlb could be an integrated marker of cardiovascular
      and renal risk in transplant recipients is unknown. PATIENTS AND METHODS: 75
      hypertensive non-proteinuric renal transplant recipients were selected.
      Antihypertensive medications were stopped for a month prior to the studies. MAlb
      (on a 24-hour urine collection), cyclosporine trough levels (CsA-L), fasting
      glucose and lipids were measured. SAP and DAP were determined with a semi
      automatic device. RESULTS: 29 patients (12 W/17M) had normal levels of
      albuminuria (Nalb: albuminuria < 30 mg/24 h) and 46 had MAlb. As compared to Nalb
      patients, those with Malb were younger (M +/- SD: 44.3 +/- 13 vs 51.2 +/- 9.7
      respectively, p = 0.009), had higher SAP (152 +/- 16 vs 146 +/- 15 mmHg, p =
      0.09) et DAP (86 +/- 11 vs 81 +/- 10 mmHg, p = 0.01). No difference in smoking
      habits, serum creatinine (125 +/- 27 vs 119 +/- 28 mumol/L), total-, HDL- and LDL
      cholesterol, triglycerides, fasting glucose, CsA-L (142 +/- 29 vs 144 +/- 26
      ng/mL), 24 h-urine urea excretion was observed. History of acute rejection
      episodes (45.7% vs 17.2%, p = 0.01) was more frequent and 24-hour natriuresis
      (192 +/- 70 vs 152 +/- 79 mmol/24 h, p < 0.01) was higher in Malb than in Nalb.
      CONCLUSION: The determinants of microalbuminuria in renal transplant recipients
      are different from those found in the general population. History of acute
      rejection episodes was more frequent in renal transplant recipients with Malb
      than in those with NAlb despite similar renal function, suggesting that Malb may
      a marker of subclinical renal lesions due to immunological aggression. The
      relationship between natriuresis and Malb suggests that sodium intake modulates
      target-organ damage associated with hypertension.

PMID- 11575236
TI  - [Relationship between vasosympathetic activity and insulin resistance in
      normotensive and mildly hypertensive obese patients].
AB  - Several studies have well demonstrated that obesity is associated with changes in
      cardiovascular vagosympathetic activity. The aim of the present work was to
      evaluate this activity in normotensive and in mildly hypertensive obese patients,
      and to correlate this activity with clinical and biological indexes of insulin
      resistance. Heart rate (HR) and systolic blood pressure (sBP) were examined by
      spectral analysis in 70 normotensive obese patients (group 1), 32 mildly
      hypertensive obese patients (group 2), and 21 controls. The high frequency peak
      of HR variations at a controlled breathing rate (vagal activity) was
      significantly reduced in both groups (p < 0.001). The mid frequency peak of sBP
      in the standing position (sympathetic activity) was similar in both groups and in
      the control group. In groups 1 and 2, the high frequency peak correlated
      negatively with age (p = 0.005 and 0.034 respectively). In group 1, the mid
      frequency peak correlated positively with fat mass, fasting plasma insulin and
      triglyceride levels, and insulin resistance index (p < or = 0.03). In group 2,
      the mid frequency peak correlated positively with fasting insulin and insulin
      resistance index (p = 0.006 and 0.007 respectively). This study shows that, in
      obese patients: 1. cardiac vagal activity is reduced in normotensive and mildly
      hypertensive subjects; 2. vascular sympathetic activity is unchanged in means but
      may be increased as a consequence of adiposity, hyperinsulinemia and insulin
      resistance, and this increase is likely to be involved in the increase of blood
      pressure.

PMID- 11575235
TI  - [Altered heart rate variability but preserved temporal relationship with sleep
      stages in a patient with primary aldosteronism].
AB  - OBJECTIVE: In a previous study, we found oscillations in the autonomic nervous
      system activity--as estimated by spectral analysis of R-R intervals--strongly
      linked to the non-rapid-eye movement (NREM)--REM sleep cycles, with low
      sympathetic activity during NREM sleep and predominant sympathetic activity
      during REM sleep. In the present study we established the 5-min nighttime
      profiles in various measures of heart rate variability (HRV) in one patient with
      primary aldosteronism before and after successful surgery of Conn adenoma.
      METHODS: One patient (female, 36 years old) with primary aldosteronism underwent
      two experimental nights a few weeks before and after surgery by coeliscopy in
      which sleep and cardiac recordings were made. Power spectral analysis was
      performed on ectopic-free R-R intervals with a fast Fourier transform. We
      calculated also the standard deviation of normal R-R intervals (SDNN) and the
      root mean square difference among successive R-R intervals (RMSSD). RESULTS:
      While removal of adenoma resulted in a rapid complete normalization of blood
      pressure and classical signs and biological symptoms of aldosterone
      hypersecretion, HRV profile did not changed a few weeks after surgery. The
      overnight SDNN was low although not abnormal at 38 and 33 ms before and after
      surgery respectively vs 58 +/- 15 ms (33 to 83) in normal female controls. RMSSD
      was low although not abnormal at 33 and 31 ms before and after surgery
      respectively vs 60 +/- 20 ms (20 to 105). The total spectrum power was low
      although not abnormal at 2.3 and 1.8 ms2 before and after surgery, respectively
      vs 3.2 +/- 1.1 ms2 (1.4 to 4.9). One out of the 8 controls had comparable or
      lower SDNN (33 ms), RMSSD (20 ms) and total power (1.4 ms2) values. While LF/HF
      ratio was comparable, the VLF (0.003-0.04 Hz) and LF (0.04-0.15 Hz) relative
      power were decreased and increased respectively in the patient compared in
      controls. Despite this reduced HRV, the normal temporal relationship of spectral
      parameters with specific sleep stages was preserved. CONCLUSION: Altered HRV with
      normal temporal relationships with specific sleep stages was observed in a
      patient with primary hyperaldosteronism. This HRV profile did not changed 20
      weeks after successful surgery i.e. complete remission of classical signs and
      symptoms of aldosterone hypersecretion.

PMID- 11575237
TI  - [Arterial rigidity and cardiovascular vagosympathetic activity in normotensive
      and hypertensive obese patients and type 2 diabetics].
AB  - An increase in arterial rigidity is associated with a poor cardiovascular
      prognosis. Several studies have suggested that an increase in sympathetic
      activity may be involved in essential hypertension. We have recently shown that
      vagal control of heart rate (HR) variations during standardised tests is altered
      in normotensive obese and diabetic patients. The aim of the present study was to
      compare cardiovascular vagosympathetic activity in obese and type 2 diabetic
      patients, either normotensive or hypertensive, and to investigate the
      relationship between pulse pressure (an index of arterial rigidity) and
      sympathetic activity in this population. Seventy normotensive obese and 32 mildly
      hypertensive obese patients, 18 normotensive type 2 diabetic patients and 14
      mildly hypertensive type 2 diabetic patients were compared with 21 control
      subjects. Finapres studied HR and blood pressure variations. In the four groups,
      during a 6-min period at a controlled breathing rate, the high frequency peak of
      HR variations was significantly reduced (p < 0.001). The mid-frequency peak of
      systolic BP variations in the standing position, which depends on sympathetic
      activity, did not differ significantly between the four groups and control
      subjects. In obese and diabetic hypertensive patients, this peak correlated
      significantly with pulse pressure measured in the lying position (r = 0.379; p =
      0.043 and r = 0.81; p < 0.0001, respectively). This study 1, confirms that vagal
      control of HR variations is reduced to a similar extent in obese and diabetic
      patients; and 2, suggests that cardiovascular sympathetic activity is relatively
      increased in these patients without significant difference between normotensive
      and hypertensive patients, but interestingly that the increase in arterial
      rigidity is associated with a higher sympathetic activity.

PMID- 11575238
TI  - Prevalence of anemia in children 6-59 months old in the state of Pernambuco,
      Brazil.
AB  - OBJECTIVE: To determine the prevalence of anemia in children 6-59 months old in
      Pernambuco, a state in northeastern Brazil, so as to help guide health and
      nutrition policies there. METHODS: In 1997 a representative sample of 777 young
      children had their hemoglobin concentration measured. The sampling process was in
      three stages. First, 18 municipalities were randomly selected to represent the
      state and its three geographic areas (metropolitan region of Recife, urban
      interior, and rural interior). Next, using census lists, 45 census sectors were
      randomly chosen. Finally, 777 children aged 6-59 months old were selected. Blood
      was collected by venipuncture, and hemoglobin was measured with a portable
      hemoglobinometer. In the analysis, prevalence was weighted to reflect the census
      age distribution. RESULTS: The prevalence of anemia among children 6-59 months
      old was 40.9% for the state as a whole. Prevalence in the metropolitan region of
      Recife was 39.6%, and it was 35.9% in the urban interior. The rural interior had
      the highest prevalence, 51.4%. Prevalence was twice as high in children aged 6-23
      months as among those 24-59 months old, 61.8% vs. 31.0% (chi 2 = 77.9, P <
      0.001). The mean hemoglobin concentrations in the younger and older age groups
      were 10.4 g/dL (standard deviation (SD) = 1.5) and 11.4 g/dL (SD = 1.4),
      respectively. There was no statistically significant difference between the sexes
      in terms of prevalence. CONCLUSIONS: This is the first statewide assessment of
      anemia prevalence among young children in Brazil. Given the very high prevalence
      of anemia among the children studied in Pernambuco, especially those in the age
      group of 6-23 months, public health interventions are needed.

PMID- 11575239
TI  - [Exposure to fluorides from drinking water in the city of Aguascalientes,
      Mexico].
AB  - OBJECTIVE: Determine the fluoride content in all the wells that supply drinking
      water to the city of Aguascalientes, Mexico, in order to establish the
      population's degree of exposure. METHODS: The fluoride content of the 126 wells
      that supply drinking water to the city of Aguascalientes was determined, using
      the SPADNS method, in accordance with two Mexican regulations, NMX-AA-77-1982 and
      NMX-014-SSAI-1993. Using that data, we created fluoride isopleth maps showing the
      distribution of fluoride concentrations in the water supplies for the city of
      Aguascalientes. We also estimated exposure doses for the city's inhabitants.
      RESULTS: The mean analysis uncertainty was 3.9%. Seventy-three wells had a
      fluoride concentration of" 1.5 mg/L, which was the maximum permissible value set
      by the Mexican standards then in effect. All the maximum exposure doses surpassed
      the minimum risk level set by Agency for Toxic Substances and Disease Registry
      (ATSDR) of the Department of Health and Human Services of the United States of
      America. In the children under 1 year of age, even the minimum does was slightly
      higher than the ATSDR risk level. CONCLUSIONS: From estimating the fluoride
      exposure doses caused by water consumption in the city of Aguascalientes and
      comparing those doses with ones from other states in Mexico, we concluded that
      the fluoride intake in Aguascalientes represents a potential risk for
      inhabitants' health. The fluoride content of the city's drinking water should be
      reduced to 0.69 mg/L.

PMID- 11575241
TI  - Hearing aids and services for developing countries.

PMID- 11575240
TI  - [Preventing opportunistic infections in patients infected with the human
      immunodeficiency virus].
AB  - Highly active antiretroviral therapy (HAART), which has been provided since 1995
      to patients infected with human immunodeficiency virus (HIV), has produced
      noticeable results in regard to preventing opportunistic infections in this
      population. Nevertheless, it is still useful to administer specific prophylactic
      treatment against opportunistic infections in patients treated with HAART and
      also in patients who do not respond to HAART or who cannot or do not wish to take
      that treatment. Prophylactic treatment can be halted when, due to HAART, there is
      a sustained increase in the CD4+ T-lymphocytes count (that count indicates the
      degree of susceptibility that a person has to opportunistic infections).
      Guidelines for preventing opportunistic infections were developed in 1995 by the
      United States Public Health Service and the Infectious Diseases Society of
      America, and they have been reviewed periodically. The last review, done in 1999,
      marked the introduction of important changes regarding clinical parameters to
      halt primary and secondary prophylaxis against Pneumocystis carinii pneumonia,
      Toxoplasma gondii, and Mycobacterium avium complex. These changes, along with the
      latest information concerning the transmission of human herpesviruses,
      immunization of children infected with HIV or exposed to the virus, and certain
      drug interactions, are the major focus of this review.

PMID- 11575242
TI  - [Obesity and its patterns in the region].

PMID- 11575243
TI  - A comparison of distribution curves of body mass index from Brazil and the United
      States for assessing overweight and obesity in Brazilian adolescents.
AB  - OBJECTIVE: To assess the validity of recommendations for use of the 85th and 95th
      percentiles of body mass index (BMI) of the population in the United States of
      America as a screening tool to assess overweight/obesity in adolescents. METHODS:
      We investigated the relation between BMI and percent body fat in 1,540
      adolescents (717 males and 823 females) aged 10 to 17.9 years old from a private
      high school in Niteroi, a city in the state of Rio de Janeiro, Brazil. We used
      bioelectric impedance, with the appropriate equations for adolescents, to
      estimate percent body fat, which served as the gold standard (30% for girls and
      25% for boys) to calculate the sensitivity and specificity of the 85th and 95th
      percentiles of the United States and Brazilian distribution curves of BMI.
      RESULTS: Sensitivity and specificity were high (above 80%) for the Niteroi boys,
      except for the 85th percentile of the Brazilian curve (specificity = 61.8%) and
      for the 95th percentile of the United States curve (sensitivity = 55.4%). For the
      Niteroi girls, the 85th- and 95th-percentile BMI cutoff points, from both the
      United States and Brazilian curves, showed low sensitivity, and that sensitivity
      decreased with age. Specificity was high for the girls, and much higher than it
      was for the boys. CONCLUSIONS: These data suggest that using BMI to screen for
      overweight/obesity in adolescents can generate a high percentage of false
      positives for Niteroi boys and an even higher percentage of false-negatives for
      Niteroi girls. A more universal approach to using anthropometric measures to
      screen for overweight/obesity should be developed, preferably linked to stages of
      maturation.

PMID- 11575244
TI  - [A model of primary prevention of sexually transmitted diseases and HIV/AIDS in
      adolescents].
AB  - OBJECTIVE: To develop, apply, and evaluate an educational model for the primary
      prevention of sexually transmitted diseases (STDs) and acquired immunodeficiency
      syndrome (AIDS) that was based on the sexual knowledge, attitudes, and practices
      (KAPs) of adolescents and on their perceptions and behaviors in this area, with
      the ultimate goal of helping develop educational tools to prevent infection with
      STDs and the human immunodeficiency virus (HIV). METHODS: An STD/HIV/AIDS primary
      prevention model was applied with adolescent schoolchildren (12 to 15 years old)
      in the canton of Santo Domingo de los Colorados, Ecuador. Two groups with similar
      characteristics were formed: the experimental group, with 358 students, and the
      control group, with 288 students. Schools were selected according to inclusion
      criteria, and adolescents at each school were chosen at random. A discussion
      guide was applied with 16 focus groups, and the resulting information was used to
      prepare a KAP survey. After being validated, the KAP survey was applied to the
      experimental group and to the control group. A prevention education program
      geared to students and teachers was implemented with the experimental group.
      Eight months later a second KAP survey was done with the experimental group and
      the control group. The differences in KAPs before and after the intervention were
      evaluated using the chi-square test. RESULTS: There were no statistically
      significant differences between the two groups before the intervention, but
      afterwards the differences were statistically significant (P = 0.012), with an
      increase in the knowledge of sexuality and STDs/AIDS in the experimental group,
      even though the long-term behavior changes have not been evaluated. CONCLUSIONS:
      This study validated a multifactorial STD/AIDS prevention model adapted to the
      reality of adolescents, and it suggests the possibility of extrapolating this
      experience more broadly to contexts similar to those of this Ecuador population.

PMID- 11575245
TI  - [Allocation of health care resources in the state of Santa Catarina, Brazil: a
      contribution to a discussion on health financing].
AB  - OBJECTIVE: To describe the health situation in municipalities in the state of
      Santa Catarina, Brazil, in 1996, and to investigate how that correlated with
      federal health spending in 1997. METHODS: Multiple regression analysis was used
      to investigate the association between federal health care funding and
      proportional mortality, supply of health services (hospitals and outpatient
      clinics), and the municipality's population (number of inhabitants). Also
      investigated was the association between mortality from broad groups of causes
      and socioeconomic structure, supply of health services, and the municipality's
      population. RESULTS: The multiple regression analysis showed an association
      between proportional mortality due to: 1) infectious diseases and: infant
      mortality, number of non-doctor medical professionals per 10,000 inhabitants, and
      number of physicians per 10,000 inhabitants (negative association); 2) chronic
      degenerative diseases and: percentage of individuals 60 years and older, infant
      mortality (negative association), and number of non-doctor medical professionals
      per 10,000 inhabitants (negative association); and 3) external causes of death
      and: the municipality's population, number of hospitals per 10,000 inhabitants
      (negative association), and percentage of children younger than 1 year. Health
      spending per inhabitant in 1997 was mainly associated with the municipality's
      population, number of outpatient clinics per 10,000 inhabitants, Swaroop and
      Uemura mortality rate, and deaths due to chronic degenerative diseases in 1996.
      CONCLUSIONS: Municipalities with a better morbidity and mortality profile and a
      better health services structure received more federal health care resources. To
      improve this situation, special strategies should be considered in order to
      ensure additional resources for municipalities that have poorer health
      indicators.

PMID- 11575246
TI  - Non-metal post systems.
AB  - For many years metals, whether cast or prefabricated, have been exclusively used
      to construct posts as foundations for indirect restorations. Developments in
      composite and ceramic materials have resulted in the introduction of metal-free
      post systems as alternatives. This article provides an overview of the systems
      currently available, gives guidance on their use, and discusses some of the
      principles underlying the clinical performance of posts.

PMID- 11575247
TI  - Update on orthognathic surgery.
AB  - This article gives an account of contemporary methods in orthognathic surgery,
      highlighting which patients are appropriate for such surgery. In order to make
      the case relevant, a single patient is tracked through her orthodontic treatment,
      surgery and final outcome.

PMID- 11575248
TI  - Treatment planning for the problem patient: restorative, ethical, legal and
      psychological perspectives. Case 3: Mary.
AB  - Mary' is the third of a series of four articles that aims to look at some of the
      problems patients may present with when they visit their dentist. Each article
      starts with a brief scenario about the hypothetical patient and his/her clinical
      problems. As well as the clinical problem, each case also raises ethical, legal
      or psychological problems. All of these issues are discussed and possible
      management strategies and treatment options investigated.

PMID- 11575249
TI  - What, when and how to back up your data.
AB  - This article defines and describes the process of backing up data files, which
      should be undertaken by anyone who routinely uses a computer. The important
      points to be considered when developing a backup strategy are explained and a
      resume given of the backup devices currently available.

PMID- 11575250
TI  - The neural mechanisms of oral and facial pain.
AB  - Pain is a complex and variable phenomenon that can be influenced by many factors.
      The neural pathways serving pain are not passive conduits, but are part of a
      dynamic system which can result in different levels of pain resulting from
      similar injuries under different circumstances. The passage of signals in these
      pathways may be inhibited or enhanced at almost any level, from the peripheral
      sensory receptors to the higher centres of the brain. This review will describe
      recent developments in our understanding of these mechanisms and how this
      knowledge may be used in controlling pain.

PMID- 11575251
TI  - Tax-free sale of a dental practice.

PMID- 11575252
TI  - Award of the G. Whitaker International Burns Prize for 2001, Palermo, Italy.

PMID- 11575253
TI  - [Periodontal status among the population of Geneva, Vaud and Neuchatel].
AB  - The aim of the present study was to evaluate the periodontal status among the
      population of Geneva, Vaud and Neuchatel. A representative sample of the
      population was selected on the basis of age, sex and location. The rate of
      participation was 51%. In total, 268 subjects were examined; this corresponds to
      1:4000 inhabitants. The results showed that a majority of the subjects presented
      signs of inflamed gingiva. Moderate periodontitis affected a large proportion of
      the population, whereas severe periodontitis affected only a small percentage of
      subjects. We observed that the severity of periodontal destruction increased with
      age and there was no difference between both sexes. The findings revealed that
      most of the periodontal treatment needs could be provided by general dentists.
      Complex treatment needs were limited in extent.

PMID- 11575254
TI  - [Styloid process: radiograph and craniomandibular dysfunction (CMD)].
AB  - The aim of the study was to investigate the suitability of orthopantomograms for
      measuring the length of the styloid process (SP), and to determine the frequency
      of elongated SP in patients with craniomandibular dysfunction (CMD). For 350
      patients, two ortho-pantomograms were available, produced by a SIEMENS Orthophos
      5 using programs P1 and P6, respectively, plus a craniomandibular function index.
      The SP length measurements from the orthopantomograms and the palpation findings
      were correlated. In 34,7% of the 700 orthopantomograms the SP was measurable. The
      mean length was determined to be 29.1 mm in OPT1 films on both sides. In the OPT6
      films the length values were 30.1 mm on the right, and 30.4 mm on the left side.
      In CMD patients there was no evidence of the SP causing the complaints. Two
      conclusions can be made: For epidemiologic studies on the length of the styloid
      process, the orthopantomogram is of limited use. In CMD patients the elongated
      styloid process is of negligible importance as a cause of complaints.

PMID- 11575255
TI  - Technical framework for using digital interactive television in home telecare.

PMID- 11575256
TI  - Photo quiz. Lesion on the arm of a returning traveler. Cutaneous leishmaniasis.

PMID- 11575257
TI  - Photo quiz. Healthy student with a papule. New World cutaneous leishmaniasis.

PMID- 11575258
TI  - China launches drive to curb HIV in blood.

PMID- 11575259
TI  - India: Cipla launches 3-in-1 AIDS pill.

PMID- 11575260
TI  - Adverse reaction to anti-tetanus human gammaglobulin.

PMID- 11575261
TI  - Temporary henna tattoos: an increasing risk of contact dermatitis.

PMID- 11575262
TI  - Ongoing clinical trials.

PMID- 11575263
TI  - Dilated cardiomyopathy in thyrotoxicosis and Moyamoya disease.
AB  - A 37-year-old Korean woman was admitted at 31 weeks gestation with exertional
      dyspnea. Three years ago she was diagnosed as having Graves' disease.
      Thyrotoxicosis-induced dilated cardiomyopathy was diagnosed by echocardiography.
      During management, a first attack of seizure occurred. Brain MRI and MRA showed
      occlusion of both internal carotid arteries, which confirmed the diagnosis of
      Moyamoya disease. Coexistence of dilated cardiomyopathy in thyrotoxicosis and
      Moyamoya disease is rare and the pathogenic correlation is discussed.

PMID- 11575264
TI  - Apical hypertrophic cardiomyopathy mimics acute coronary syndrome.
AB  - We present a case who was initially thought to have an acute coronary syndrome
      but who was later diagnosed to have an apical hypertrophic cardiomyopathy.
      Interestingly, the diagnosis could be established with left heart
      catheterization, not echocardiography.

PMID- 11575265
TI  - Enoxaparin in unstable angina patients with renal failure.
AB  - The dosage of the subcutaneous low molecular weight heparin enoxaparin in
      unstable angina patients undergoing coronary angiogram and coronary angioplasty
      depends clearly on the renal function. It should be significantly reduced to 64%
      of the standard dose (1 mg/kg per 12 h) in patients with severe renal failure
      (creatinine clearance<30 ml/min) to provide a safe anticoagulant profile.

PMID- 11575266
TI  - A case of severe hypoglycemia due to pimobendan.

PMID- 11575267
TI  - Congenital bilateral aplasia of external iliac arteries.
AB  - A child with bilateral aplasia of external iliac arteries with normal internal
      iliac arteries, demonstrated by vascular Doppler and digital subtraction
      angiography is presented. Popliteal artery is reformed by collaterals. This
      anomaly is extremely rare.

PMID- 11575268
TI  - Inverse association between sense of humor and coronary heart disease.
AB  - Prospective studies have suggested that antisocial Type A personality traits may
      be associated with an increased incidence of coronary heart disease (CHD).
      However, few data have addressed whether more favorable personality
      characteristics may be inversely correlated with CHD. Therefore, two standardized
      questionnaires designed to either assess anger and hostility or to measure the
      propensity to laugh under a variety of situations encountered in everyday life,
      were administered to 300 consecutive subjects. Compared to controls, CHD subjects
      were significantly less likely to experience laughter during daily activities,
      surprise situations or social interactions (P<0.005). Logistic regression
      analysis revealed an inverse correlation between humor and CHD, even after
      adjustment for other covariates, including hypercholesterolemia, hypertension and
      diabetes mellitus (P=0.03). A significant inverse association was also observed
      between humor production and antisocial Type A personality traits (P=0.0001).
      These data extend previous observations linking antisocial Type A personality
      traits to CHD and raise the possibility that the propensity to laugh may
      contribute to cardioprotection.

PMID- 11575269
TI  - Anomalous left circumflex coronary artery from pulmonary artery and left anterior
      descending artery from right coronary artery.

PMID- 11575270
TI  - Relevance of simultaneous ST segment elevation and depression in an exercise
      treadmill test.
AB  - Simultaneous ST segment elevation and depression recorded during an exercise
      treadmill test and its correlation with coronary angiogram is a new finding that
      does not find a place in medical literature. We conclude that in the presence of
      simultaneous ST segment elevation and ST segment depression during exercise
      treadmill test (1) the localizing value of isolated ST elevation is lost and (2)
      there is severe triple vessel disease warranting early intervention.

PMID- 11575271
TI  - Simultaneous intervention of five coronary and extra-coronary vessels.

PMID- 11575272
TI  - Pole position.

PMID- 11575273
TI  - Edging forward.

PMID- 11575274
TI  - Caught in the actin.

PMID- 11575275
TI  - The replication connection.

PMID- 11575276
TI  - Escape from death.

PMID- 11575277
TI  - Summaries for patients. Predicting risk for prolonged high INR after too much
      anticoagulation.

PMID- 11575278
TI  - Summaries for patients. Diagnosis of renal artery stenosis.

PMID- 11575280
TI  - Summaries for patients. Bupropion to prevent relapse in people who quit cigarette
      smoking.

PMID- 11575279
TI  - Summaries for patients. Itraconazole and amphotericin B to treat fungal
      infections in patients with cancer who are receiving chemotherapy.

PMID- 11575281
TI  - Summaries for patients. Fatal inflammatory condition in a patient with a variant
      bacterial strain.

PMID- 11575282
TI  - Fatal reactivation of cytomegalovirus infection after use of rituximab for a post
      transplantation lymphoproliferative disorder.

PMID- 11575283
TI  - Preventable deaths and injuries during magnetic resonance imaging.

PMID- 11575284
TI  - Selective postoperative inhibition of gastrointestinal opioid receptors.
AB  - BACKGROUND: Postoperative recovery of gastrointestinal function and resumption of
      oral intake are critical determinants of the length of hospital stay. Although
      opioids are effective treatments for postoperative pain, they contribute to the
      delayed recovery of gastrointestinal function. METHODS: We studied the effects of
      ADL 8-2698, an investigational opioid antagonist with limited oral absorption
      that does not readily cross the blood-brain barrier, on postoperative
      gastrointestinal function and the length of hospitalization. We randomly assigned
      79 patients--including 1 whose surgery was canceled--to receive one capsule
      containing 1 mg or 6 mg of ADL 8-2698 or an identical-appearing placebo capsule
      two hours before major abdominal surgery and then twice daily until the first
      bowel movement or until discharge from the hospital. Data were analyzed for 26
      patients in each of the three groups; all received opioids for postoperative pain
      relief. Observers who were unaware of the group assignments evaluated the
      outcomes. RESULTS: Fifteen patients underwent partial colectomy and 63 underwent
      total abdominal hysterectomy. Patients given 6 mg of ADL 8-2698 had significantly
      faster recovery of gastrointestinal function than those given placebo. The median
      time to the first passage of flatus decreased from 70 to 49 hours (P=0.03), the
      median time to the first bowel movement decreased from 111 to 70 hours (P=0.01),
      and the median time until patients were ready for discharge decreased from 91 to
      68 hours (P=0.03). Effects in the group that received 1 mg of ADL 8-2698 were
      less pronounced. CONCLUSIONS: Selective inhibition of gastrointestinal opioid
      receptors by an antagonist with limited oral absorption that does not readily
      cross the blood-brain barrier speeds recovery of bowel function and shortens the
      duration of hospitalization.

PMID- 11575285
TI  - Effects of inhaled glucocorticoids on bone density in premenopausal women.
AB  - BACKGROUND: Inhaled glucocorticoids are the most commonly used medications for
      the long-term treatment of patients with asthma. Whether long-term therapy with
      inhaled glucocorticoids reduces bone mass, as oral glucocorticoid therapy does,
      is controversial. In a three-year prospective study, we examined the relation
      between the dose of inhaled glucocorticoids and the rate of bone loss in
      premenopausal women with asthma. METHODS: We studied 109 premenopausal women, 18
      to 45 years of age, who had asthma and no known conditions that cause bone loss
      and who were treated with inhaled triamcinolone acetonide (100 microg per puff).
      We measured bone density by dual-photon absorptiometry at base line, at six
      months, and at one, two, and three years. Serum osteocalcin and parathyroid
      hormone and urinary N-telopeptide, cortisol, and calcium excretion were measured
      serially. We measured inhaled glucocorticoid use by means of monthly diaries,
      supported by the use of an automated actuator-monitoring device. RESULTS: Inhaled
      glucocorticoid therapy was associated with a dose-related decline in bone density
      at both the total hip and the trochanter of 0.00044 g per square centimeter per
      puff per year of treatment (P= 0.01 and P=0.005, respectively). No dose-related
      effect was noted at the femoral neck or the spine. Even after the exclusion of
      all women who received oral or parenteral glucocorticoids at any time during the
      study, there was still an association between the decline in bone density and the
      number of puffs per year of use. Serum and urinary markers of bone turnover or
      adrenal function did not predict the degree of bone loss. CONCLUSIONS: Inhaled
      glucocorticoids lead to a dose-related loss of bone at the hip in premenopausal
      women.

PMID- 11575286
TI  - Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate
      cancer.
AB  - BACKGROUND: Treatment with a gonadotropin-releasing hormone agonist decreases
      bone mineral density and increases the risk of fracture in men with prostate
      cancer. We conducted a controlled study of the prevention of osteoporosis in men
      undergoing treatment with a gonadotropin-releasing hormone agonist. METHODS: In a
      48-week, open-label study, we randomly assigned 47 men with advanced or recurrent
      prostate cancer and no bone metastases to receive either leuprolide alone or
      leuprolide and pamidronate (60 mg intravenously every 12 weeks). Bone mineral
      density of the lumbar spine and the proximal femur was measured by dual-energy x
      ray absorptiometry. Trabecular bone mineral density of the lumbar spine was
      measured by quantitative computed tomography. Forty-one men completed the study.
      RESULTS: In men treated with leuprolide alone, the mean (+/-SE) bone mineral
      density decreased by 3.3+/-0.7 percent in the lumbar spine, 2.1+/-0.6 percent in
      the trochanter, and 1.8+/-0.4 percent in the total hip, and the mean trabecular
      bone mineral density of the lumbar spine decreased by 8.5+/-1.8 percent (P<0.001
      for each comparison with the base-line value). In contrast, the mean bone mineral
      density did not change significantly at any skeletal site in men treated with
      both leuprolide and pamidronate. There were significant differences between the
      two groups in the mean changes in bone mineral density at 48 weeks in the lumbar
      spine (P<0.001), trochanter (P = 0.003), total hip (P=0.005), and trabecular bone
      of the lumbar spine (P=0.02). CONCLUSIONS: Pamidronate prevents bone loss in the
      hip and lumbar spine in men receiving treatment for prostate cancer with a
      gonadotropin-releasing hormone agonist.

PMID- 11575287
TI  - Deep-brain stimulation of the subthalamic nucleus or the pars interna of the
      globus pallidus in Parkinson's disease.
AB  - BACKGROUND: Increased neuronal activity in the subthalamic nucleus and the pars
      interna of the globus pallidus is thought to account for motor dysfunction in
      patients with Parkinson's disease. Although creating lesions in these structures
      improves motor function in monkeys with induced parkinsonism and patients with
      Parkinson's disease, such lesions are associated with neurologic deficits,
      particularly when they are created bilaterally. Deep-brain stimulation simulates
      the effects of a lesion without destroying brain tissue. METHODS: We performed a
      prospective, double-blind, crossover study in patients with advanced Parkinson's
      disease, in whom electrodes were implanted in the subthalamic nucleus or pars
      interna of the globus pallidus and who then underwent bilateral high-frequency
      deep-brain stimulation. We compared scores on the motor portion of the Unified
      Parkinson's Disease Rating Scale when the stimulation was randomly assigned to be
      turned on or off. We performed unblinded evaluations of motor function
      preoperatively and one, three, and six months postoperatively. RESULTS:
      Electrodes were implanted bilaterally in 96 patients in the subthalamic-nucleus
      group and 38 patients in the globus-pallidus group. Three months after the
      procedures were performed, double-blind, crossover evaluations demonstrated that
      stimulation of the subthalamic nucleus was associated with a median improvement
      in the motor score (as compared with no stimulation) of 49 percent, and
      stimulation of the pars interna of the globus pallidus with a median improvement
      of 37 percent (P<0.001 for both comparisons). Between the preoperative and six
      month visits, the percentage of time during the day that patients had good
      mobility without involuntary movements increased from 27 percent to 74 percent
      (P<0.001) with subthalamic stimulation and from 28 percent to 64 percent
      (P<0.001) with pallidal stimulation. Adverse events included intracranial
      hemorrhage in seven patients and infection necessitating removal of the leads in
      two. CONCLUSIONS: Bilateral stimulation of the subthalamic nucleus or pars
      interna of the globus pallidus is associated with significant improvement in
      motor function in patients with Parkinson's disease whose condition cannot be
      further improved with medical therapy.

PMID- 11575288
TI  - Images in clinical medicine. Pneumatosis coli and colonic intussusception.

PMID- 11575289
TI  - A computerized reminder system to increase the use of preventive care for
      hospitalized patients.
AB  - BACKGROUND: Although they are effective in outpatient settings, computerized
      reminders have not been proved to increase preventive care in inpatient settings.
      METHODS: We conducted a randomized, controlled trial to determine the effects of
      computerized reminders on the rates at which four preventive therapies were
      ordered for inpatients. During an 18-month study period, a computerized system
      processed on-line information for all 6371 patients admitted to a general
      medicine service (for a total of 10,065 hospitalizations), generating preventive
      care reminders as appropriate. Physicians who were in the intervention group
      viewed these reminders when they were using a computerized order-entry system for
      inpatients. RESULTS: The reminder system identified 3416 patients (53.6 percent)
      as eligible for preventive measures that had not been ordered by the admitting
      physician. For patients with at least one indication, computerized reminders
      resulted in higher adjusted ordering rates for pneumococcal vaccination (35.8
      percent of the patients in the intervention group vs. 0.8 percent of those in the
      control group, P<0.001), influenza vaccination (51.4 percent vs. 1.0 percent, P<
      0.001), prophylactic heparin (32.2 percent vs. 18.9 percent, P<0.001), and
      prophylactic aspirin at discharge (36.4 percent vs. 27.6 percent, P<0.001).
      CONCLUSIONS: A majority of hospitalized patients in this study were eligible for
      preventive measures, and computerized reminders significantly increased the rate
      of delivery of such therapies.

PMID- 11575290
TI  - Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of
      the young.

PMID- 11575291
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 30-2001. A 22-year-old man with hyperthyroidism, fever, abdominal
      pain, and arthralgia.

PMID- 11575292
TI  - An opioid antagonist for postoperative ileus.

PMID- 11575293
TI  - Bone loss accompanying medical therapies.

PMID- 11575294
TI  - Making it easy to do it right.

PMID- 11575295
TI  - Trastuzumab and breast cancer.

PMID- 11575296
TI  - Trastuzumab and breast cancer.

PMID- 11575297
TI  - Trastuzumab and breast cancer.

PMID- 11575298
TI  - Trastuzumab and breast cancer.

PMID- 11575299
TI  - Effects of beta-blocker therapy in severe chronic heart failure.

PMID- 11575300
TI  - Effects of beta-blocker therapy in severe chronic heart failure.

PMID- 11575301
TI  - A long-term survivor with the immune dysregulation, polyendocrinopathy,
      enteropathy, X-linked syndrome.

PMID- 11575302
TI  - Endoscopic treatments for GERD: are they ready for prime time?

PMID- 11575303
TI  - Is it colic or is it gastroesophageal reflux?

PMID- 11575304
TI  - Clinical quiz. Gaucher disease.

PMID- 11575305
TI  - What's new in eosinophilic homing? Something is in the air.

PMID- 11575306
TI  - DNA microarray gene expression analysis technology and its application to
      neurological disorders.
AB  - DNA microarray technology is currently an area of great interest. Also called
      "genechip" technology, it incorporates molecular genetics and computer science on
      a massive scale. This technology can rapidly provide a detailed view of the
      simultaneous expression of entire genomes and provide new insights into gene
      function, disease pathophysiology, disease classification, and drug development.
      In this review, the author discusses the basic theory behind genechip and the
      other biologic chip technologies, their limitations given the current state of
      biologic knowledge and computational abilities, and their potential applications
      to the understanding of neurologic disorders.

PMID- 11575307
TI  - Welding-related parkinsonism: clinical features, treatment, and pathophysiology.

PMID- 11575308
TI  - Zoonotic sporotrichosis. Transmission to humans by infected domestic cat
      scratching: report of four cases in Sao Paulo, Brazil.
AB  - BACKGROUND: Sporotrichosis is a chronic, granulomatous, deep mycosis caused by
      the dimorphic fungus Sporothrix schenckii that usually results in indolent
      cutaneous lesions. OBJECTIVE: To describe four cases of human sporotrichosis
      transmitted by domestic cats in south-eastern Brazil. METHODS: Confirmation of
      the diagnosis was performed by histopathology, culture, and/or inoculation of
      hamsters. RESULTS: In all cases, the clinical findings in both cat and human
      groups were highly distinctive of the disease. In all human cases, there was a
      previous history of cat scratching before the development of lymphocutaneous
      lesions. Histopathology of the human lesions demonstrated the classical
      granulomatous and exudative pattern with scarce or absent fungal elements.
      Conversely, in cats, the cutaneous lesions were multiple, extensive, necrotic,
      exudative, and ulcerated. Histopathology revealed a widespread histiocytic
      reaction with a large number of fungal organisms. Disseminated lymphatic and
      visceral mycotic infection was observed in two necropsied cats. CONCLUSIONS:
      Domestic cats may be an important carrier of agents of sporotrichosis to humans.

PMID- 11575310
TI  - From the Centers for Disease control and Prevention. National, state, and urban
      area vaccination coverage levels among children aged 19-35 months--United States,
      2000.

PMID- 11575309
TI  - From the Centers for Disease control and Prevention. Temporal variations in
      school-associated student homicide and suicide events--United States, 1992-1999.

PMID- 11575311
TI  - From the Centers for Disease control and Prevention. Effectiveness of a middle
      school vaccination law--California, 1999-2001.

PMID- 11575312
TI  - From the Centers for Disease control and Prevention. Norwalk-like virus outbreaks
      at two summer camps--Wisconsin, June 2001.

PMID- 11575313
TI  - JAMA patient page. Antibiotics.

PMID- 11575314
TI  - Mortality after discharge from intensive care. Only normalisation of physiology
      will reduce risk of mortality after discharge.

PMID- 11575315
TI  - Mortality after discharge from intensive care. Research in intensive care needs
      to find balance between scientific method and ethics.

PMID- 11575316
TI  - Mortality after discharge from intensive care. Only community debate on
      appropriate end of life care will limit ballooning budget.

PMID- 11575317
TI  - Dysfunctional breathing and asthma. Trial shows benefits of Buteyko breathing
      techniques.

PMID- 11575318
TI  - Dysfunctional breathing and asthma. Panic disorder needs to be considered.

PMID- 11575319
TI  - Report may lead to population collection by the back door.

PMID- 11575320
TI  - Effects of legislation restricting pack sizes of paracetamol on self poisoning.
      Authors did not look at effects on all deliberate and accidental self poisoning.

PMID- 11575321
TI  - Effects of legislation restricting pack sizes of paracetamol on self poisoning.
      Paracetamol should be packaged with its antidote.

PMID- 11575322
TI  - Bibliography. Current world literature. Critical care outcomes.

PMID- 11575323
TI  - Bibliography. Current world literature. The surgical patient.

PMID- 11575324
TI  - Bibliography. Current world literature. Pharmacology, metabolism, and nutrition.

PMID- 11575325
TI  - From the Centers for Disease Control and Prevention. Human anthrax associated
      with an epizootic among livestock--North Dakota, 2000.

PMID- 11575326
TI  - From the Centers for Disease Control and Prevention. Draft of Guidelines for the
      Prevention of Opportunistic Infections (OIs) in persons infected with human
      immunodeficiency virus.

PMID- 11575327
TI  - From the Centers for Disease Control and Prevention. Update on spectinomycin
      availability in the United States.

PMID- 11575328
TI  - From the Centers for Disease Control and Prevention. Health-related quality of
      life--Los Angeles County, California, 1999.

PMID- 11575329
TI  - JAMA patient page. Peripheral arterial disease.

PMID- 11575330
TI  - Overview: the current role of the vascular diagnostic laboratory.

PMID- 11575331
TI  - Polycystin-1: immunoaffinity isolation and characterisation by mass spectrometry.
AB  - Polycystin-1 is a putative 460 kDa membrane protein with a unique structure and
      is possibly representative of a new family of proteins. Its structure suggests an
      involvement in cell signalling and cell-matrix interactions. The amino acid
      sequence of polycystin-1 has to date been predicted from its gene sequence. This,
      to our knowledge, is the first report of the isolation and analysis of polycystin
      1 at the protein level using mass spectrometry to confirm its predicted
      structure. The availability of purified polycystin-1 will allow a new approach to
      unravelling the complexity of the cell-cell and cell-matrix interactions of this
      large molecule in normal cells and its perturbation in disease.

PMID- 11575332
TI  - Mapping the anatomy of unconsciousness--imaging anaesthetic action in the brain.

PMID- 11575333
TI  - How can we improve the outcome of oesophagectomy?

PMID- 11575334
TI  - Development of the concept of a liquid pulmonary alveolar lining layer.

PMID- 11575335
TI  - Correlating in vivo anaesthetic effects with ex vivo receptor density data
      supports a GABAergic mechanism of action for propofol, but not for isoflurane.
AB  - If the in vivo effects of anaesthesia are mediated through a specific receptor
      system, then a relationship could exist between the regional changes in brain
      metabolism caused by a particular agent and the underlying regional distribution
      of the specific receptors affected by that agent. Positron emission tomography
      data from volunteers studied while unconscious during propofol (n=8) or
      isoflurane (n=5) anaesthesia were used retrospectively to explore for evidence of
      relationships between regional anaesthetic effects on brain glucose metabolism
      and known (ex vivo) regional distribution patterns of human receptor binding
      sites. The regional metabolic reductions caused by propofol differed
      significantly from those of isoflurane. Propofol's reductions negatively
      correlated most significantly with the regional distribution of [3H]diazepam and
      [3H]flunitrazepam (benzodiazepine) binding site densities (r=-0.86, P<0.0005; r=
      0.79, P<0.005, respectively) and less strongly with [3H]naloxone (opioid) binding
      density (r=-0.69, P<0.05). Isoflurane's reductions positively correlated only
      with muscarinic (acetylcholine) binding density (r=0.85, P<0.05). These findings
      are consistent with the hypothesis that some of propofol's in vivo anaesthetic
      effects may be mediated through a GABAergic mechanism and suggest some of
      isoflurane's in vivo effects might involve antagonism of central acetylcholine
      functioning.

PMID- 11575336
TI  - Clonidine decreases propofol requirements during anaesthesia: effect on
      bispectral index.
AB  - Assessment of the effect of clonidine on depth of anaesthesia is difficult
      because clonidine combines analgesic, sedative and direct haemodynamic effects.
      We thus evaluated the influence of clonidine on the bispectral index (BIS) and
      its potential dose-sparing effect on propofol. After induction of anaesthesia
      with target-controlled infusion of propofol and obtaining an unchanged bispectral
      index (pre-BIS), clonidine 4 microg kg(-1) or placebo was administered randomly
      to 50 patients in a double-blind manner. Subsequently, if there was a decrease in
      BIS we reduced the target concentration of propofol until pre-BIS was reached.
      The pre-BIS was maintained and a remifentanil infusion was added during surgery.
      The courses of the BIS, heart rate and blood pressure were recorded and the total
      amounts of intra-operative propofol and remifentanil were determined. Assessment
      of implicit memory during anaesthesia was performed with an auditory implicit
      memory test consisting of item sequences. Administration of clonidine resulted in
      a decrease in the BIS from 45 (SD 4) to 40 (6) (P<0.001), which allowed a
      reduction of propofol target concentration from 3.3 (0.6) to 2.7 (0.7) microg ml(
      1) (P<0.001) and measured propofol concentration from 2.9 (0.6) to 2.5 (0.7) kg
      ml(-1) (P=0.009) in order to maintain the pre-BIS value. During subsequent
      surgery, propofol requirements were reduced by 20% (P=0.002) in the clonidine
      group and a similar amount of remifentanil was used in each group. The increase
      in anaesthetic depth given by clonidine can therefore be measured with bispectral
      EEG analysis and allows reduction of the propofol dose to achieve a specific
      depth of anaesthesia.

PMID- 11575337
TI  - Peri-operative risk factors for acute lung injury after elective oesophagectomy.
AB  - Acute lung injury after oesophagectomy is well recognized but the risk factors
      associated with its development are poorly defined. We analysed retrospectively
      the effect of a number of pre-, peri- and post-operative risk factors on the
      development of lung injury in 168 patients after elective oesophagectomy
      performed at a single centre. The acute respiratory distress syndrome (ARDS)
      developed in 14.5% of patients and acute lung injury in 23.8%. Mortality in
      patients developing ARDS was 50% compared with 3.5% in the remainder. Features
      associated with the development of ARDS included a low pre-operative body mass
      index, a history of cigarette smoking, the experience of the surgeon, the
      duration of both the operation and of one-lung ventilation, and the occurrence of
      a post-operative anastomotic leak. Peri-operative cardiorespiratory instability
      (measured by peri-operative hypoxaemia, hypotension, fluid and blood requirements
      and the need for inotropic support) was also associated with ARDS. Acute lung
      injury after elective oesophagectomy is associated with intraoperative
      cardiorespiratory instability.

PMID- 11575338
TI  - Comparison of pattern of breathing with other measures of induction of
      anaesthesia, using propofol, methohexital, and sevoflurane.
AB  - We assessed change of the pattern of breathing as a marker of induction of
      anaesthesia, using a method of maintaining spontaneous breathing throughout the
      induction period. We compared this index with a measure used clinically, the lash
      reflex, and measures used for drug investigations such as loss of grip of an
      object, cessation of finger tapping, and loss of arm tone. Ninety female patients
      (mean age 32 (17-63) yr, mean weight 63 (10) kg) were randomly allocated to
      induction of anaesthesia using propofol, methohexital, or sevoflurane. The i.v.
      agents were given by slow injection estimated to give an induction dose (for
      weight drop end point) in 90 s. Sevoflurane was given by progressively increasing
      the inhaled concentration to 8% so that induction should occur within 90-120 s.
      We measured time to change in breathing pattern, loss of voluntary finger
      tapping, loss of the lash reflex (tested at 15 s intervals), loss of postural
      tone in an outstretched arm, and loss of grip of a small metal cylinder held
      between finger and thumb. For methohexital and sevoflurane, the mean times for
      induction of anaesthesia occurred in the above order. With propofol, the lash
      reflex and tone were lost at the same time. The mean (SD) time to induction, by
      loss of arm tone was 64 (16) s for propofol, 83 (23) s for methohexital, and 94
      (31) s for sevoflurane. The mean time to change in breathing pattern was 47 (20)
      s for propofol, 53 (14) s for methohexital, and 78 (29) s for sevoflurane.
      Although the time to achieve each end point was different, all the end points
      (except the lash reflex) appeared to provide similar measures of induction of
      anaesthesia. The pattern of breathing is an early sign of the onset of
      anaesthesia.

PMID- 11575339
TI  - Uptake of isoflurane during prolonged clinical anaesthesia.
AB  - Recent evidence has suggested that the rate of uptake of inhalational anaesthetic
      is constant during maintenance of anaesthesia, contrary to the predictions of
      multi-compartment uptake models. We measured isoflurane uptake using a totally
      closed anaesthetic system during up to 10 h of stable anaesthesia for maxillo
      facial surgery on 12 adult patients. Liquid isoflurane was injected into the
      system under computer control to produce an end tidal concentration of 1.3 MAC of
      isoflurane. Bench tests demonstrated that the leakage from the system was less
      than 8 microl min(-1), confirming that the rate of injection of isoflurane into
      the system was a close upper bound on the patients' uptake. Anaesthetic usage for
      a 70 kg patient was 0.44e(-0.51t)+0.044e(-0.013t)+0.058e(-0.00098t) ml min(-1) of
      liquid isoflurane, where t is duration of anaesthesia in minutes. There was a
      continuing reduction in anaesthetic requirement even at the end of the period of
      study that was statistically significant. These data do not support the notion
      that isoflurane uptake is constant during stable maintenance of anaesthesia but
      is compatible with the conventional multi-compartment model of anaesthetic uptake
      and distribution.

PMID- 11575340
TI  - Effects of dexmedetomidine on adrenocortical function, and the cardiovascular,
      endocrine and inflammatory responses in post-operative patients needing sedation
      in the intensive care unit.
AB  - We have compared the effects of dexmedetomidine and propofol on endocrine,
      metabolic, inflammatory and cardiovascular responses in patients in the intensive
      care unit (ICU) after major surgery. Twenty patients who were expected to require
      8 h of post-operative sedation and ventilation were allocated randomly to receive
      either an infusion of dexmedetomidine 0.2-2.5 microg kg(-1) h(-1) or propofol 1-3
      mg kg(-1) h(-1). Arterial pressure, heart rate and sequential concentrations of
      circulating cortisol, adrenocorticotrophic hormone (ACTH), growth hormone,
      prolactin, insulin, glucose and interleukin 6 were measured. An ACTH stimulation
      test was performed in all patients who received dexmedetomidine. Heart rate was
      significantly lower in the dexmedetomidine patients. There were no differences in
      arterial pressure, cortisol, ACTH, prolactin and glucose concentrations between
      the two groups. A positive response to the ACTH stimulation test varied depending
      on the diagnostic criteria used. The insulin concentration was significantly
      lower in the dexmedetomidine group at 2 h (P=0.021), although this did not affect
      blood glucose concentrations. Growth hormone concentrations were significantly
      higher in dexmedetomidine-treated patients overall (P=0.036), but circulating
      concentrations remained in the physiological range. Interleukin 6 decreased in
      the dexmedetomidine group. We conclude that dexmedetomidine infusion does not
      inhibit adrenal steroidogenesis when used for short-term sedation after surgery.

PMID- 11575341
TI  - Does the optimization of cardiac output by fluid loading increase splanchnic
      blood flow?
AB  - We studied the effects of increasing cardiac output by fluid loading on
      splanchnic blood flow in patients with haemodynamically stabilized septic shock.
      Eight patients (five female, 39-86 yr) were assessed using a transpulmonary
      thermo-dye-dilution technique for the measurement of cardiac index (CI)
      intrathoracic blood volume (ITBV) as a marker of cardiac preload and total blood
      volume (TBV). Splanchnic blood flow was measured by the steady state indocyanine
      green technique using a hepatic venous catheter. Gastric mucosal blood flow was
      estimated by regional carbon dioxide tension (PRCO2). Hydroxyethyl starch was
      infused to increase cardiac output while mean arterial pressure was kept
      constant. In parallel, mean norepinephrine dosage could be reduced from 0.59 to
      0.33 microg kg(-1) min(-1). Mean (SD) TBV index increased from 2549 (365) to 3125
      (447) ml m(-2), as did ITBV index from 888 (167) to 1075 (266) ml m(-2) and CI
      from 3.6 (1.0) to 4.6 (1.0) litre min(-1) m(-2). Despite marked individual
      differences, splanchnic blood flow did not change significantly neither
      absolutely (from 1.09 (0.96) to 1.19 (0.91) litre min(-1) m(-2)) nor fractionally
      as part of CI (from 28.4 (19.5) to 24.9 (16.3)%). Gastric mucosal PRCO2 increased
      from 7.7 (2.6) to 8.3 (3.1) kPa. The PCO2-gap, the difference between regional
      and end-tidal PCO2, increased slightly from 3.2 (2.7) to 3.4 (3.1) kPa. Thus, an
      increase in cardiac output as a result of fluid loading is not necessarily
      associated with an increase in splanchnic blood flow in patients with stabilized
      septic shock.

PMID- 11575342
TI  - Amrinone can accelerate the cooling rate of core temperature during deliberate
      mild hypothermia for neurosurgical procedures.
AB  - We investigated the effects of i.v. amrinone on intraoperative changes of core
      temperature during deliberate mild hypothermia for neurosurgery. The patients in
      a control group (n=10) did not receive amrinone and patients in the amrinone
      group (n=10) received amrinone 5 microg kg(-1) min(-1) after a loading dose of
      1.0 mg kg(-1). Anaesthesia was maintained with nitrous oxide in oxygen, propofol
      and fentanyl. After the induction of anaesthesia, patients were cooled and
      tympanic membrane temperature was maintained at 34.5 degrees C. After completion
      of the main surgical procedures, patients were rewarmed in the operating room.
      Tympanic membrane temperatures between 30 and 90 min after cooling were
      significantly lower in the amrinone group than in the control group. During
      cooling, the times taken to cool to 35 degrees C and to the lowest temperature
      were significantly shorter in the amrinone group than in the control group. These
      results suggest that i.v. amrinone can accelerate the cooling rate of core
      temperature during deliberate mild hypothermia for neurosurgical procedures.

PMID- 11575343
TI  - Autologous blood transfusion in total knee replacement surgery.
AB  - We compared allogeneic blood usage for two groups of patients undergoing total
      knee replacement surgery (TKR). Patients were randomized to receive either their
      post-operative wound drainage as an autotransfusion (n=115) after processing or
      to have this wound drainage discarded (n=116). Allogeneic blood was transfused in
      patients of either group whose haemoglobin fell below 9 g dl(-1). Only 7% of
      patients in the autotransfusion group required an allogeneic transfusion compared
      with 28% in the control group (P<0.001). There was no hospital mortality and only
      3% mortality from all causes at the study completion, which spanned 6 months to 3
      yr. There was a higher incidence of infection requiring intervention in the
      allogeneic group (P<0.036). Total patient costs were Pound Sterling 113 greater
      in the autotransfusion group. We conclude that in this type of surgery post
      operative cell salvage is a safe and effective method for reducing allogeneic
      blood use.

PMID- 11575344
TI  - Double-blind comparison of ropivacaine 7.5 mg ml(-1) with bupivacaine 5 mg ml(-1)
      for sciatic nerve block.
AB  - Two groups of 12 patients had a sciatic nerve block performed with 20 ml of
      either ropivacaine 7.5 mg ml(-1) or bupivacaine 5 mg ml(-1). There was no
      statistically significant difference in the mean time to onset of complete
      anaesthesia of the foot or to first request for post-operative analgesia. The
      quality of the block was the same in each group. Although there was no
      statistically significant difference in the mean time to peak plasma
      concentrations the mean peak concentration of ropivacaine was significantly
      higher than that of bupivacaine. There were no signs of systemic local
      anaesthetic toxicity in any patient in either group.

PMID- 11575345
TI  - Rocuronium: high risk for anaphylaxis?
AB  - Patients suspected of anaphylaxis during anaesthesia have been referred to the
      senior author's clinic since 1974 for investigation. Since release of rocuronium
      on to the worldwide market, concern has been expressed about its propensity to
      cause anaphylaxis. We identified 24 patients who met clinical and laboratory
      (intradermal, mast cell tryptase and morphine radioimmunoassay) criteria for
      anaphylaxis to rocuronium. The incidence of rocuronium allergy in New South
      Wales, Australia has risen in parallel with sales, while there has been an
      associated fall in reactions to other neuromuscular blocking drugs. Data from
      intradermal testing suggested that rocuronium is intermediate in its propensity
      to cause allergy in known relaxant reactors compared with low-risk agents (e.g.
      pancuronium, vecuronium) and higher-risk agents (e.g. alcuronium,
      succinylcholine).

PMID- 11575346
TI  - Effects of haemoglobin-based oxygen carrier hemoglobin glutamer-200 (bovine) on
      intestinal perfusion and oxygenation in a canine hypovolaemia model.
AB  - The objective of this investigation was to study the effects of the first
      marketed haemoglobin-based oxygen carrier, Hemoglobin glutamer-200 (bovine) (Hb
      200) (Oxyglobin) on splanchnic perfusion and oxygenation in a canine model of
      acute hypovolaemia. Twelve anaesthetized dogs [mean weight 30.8 (S.D. 1.4) kg]
      were instrumented for recordings of heart rate (HR), mean arterial pressure
      (MAP), central venous pressure (CVP), cardiac output and cranial mesenteric
      arterial (CMA) and venous blood flows (CMV). Total and plasma haemoglobin (Hb),
      oxygen content and saturation, lactate concentration, pH and blood gases were
      analysed in arterial, mixed venous and mesenteric venous blood samples.
      Measurements were made before (baseline) and after 1 h of haemorrhage, after
      which animals were resuscitated with either shed blood (controls) or Hb-200 until
      HR, MAP and CVP returned to prehaemorrhage levels. Recordings were repeated
      immediately and 3 h after termination of fluid resuscitation, after which organ
      specimens were obtained for microscopic examination. Haemorrhage (average 32 ml
      kg(-1)) reduced MAP to 50 mm Hg, increased HR and systemic vascular resistance
      (SVR), and was accompanied in both the systemic and the splanchnic circulation by
      significant decreases in blood flow, Hb content and oxygen delivery (DO2), and
      lactic acidosis. In controls, all variables recovered to baseline after
      isovolaemic resuscitation with shed blood. In dogs resuscitated with a small
      volume of Hb-200 (10 ml kg(-1)), HR, MAP, CVP and CMA and CMV blood flows
      returned to baseline. However, cardiac output, total Hb, oxygen content and
      systemic and mesenteric DO2 remained depressed while SVR increased further.
      Mesenteric and systemic acid-base status recovered in both groups, and there was
      no difference in microscopic tissue damage between groups. Thus, Hb-200
      reconstituted splanchnic perfusion and oxidative metabolism in spite of
      pronounced systemic vasoconstriction and insufficient restoration of CO and DO2;
      it may improve diffusive oxygen transport in the microvasculature by virtue of
      haemodilution and its high efficiency in the uptake and release of oxygen.

PMID- 11575347
TI  - Tissue/blood and tissue/water partition coefficients for propofol in sheep.
AB  - The primary objective of this study was to determine in vivo tissue/blood
      partition coefficients of propofol for use in physiological modelling of its
      pharmacokinetics. The sheep was used as an animal model. In the main series of
      experiments, crossbred ewes received a bolus of propofol 1% (Diprivan) followed
      by an infusion during which blood concentrations were measured at intervals.
      After 2 h, the sheep were killed with an injection of potassium chloride, and
      tissue samples were taken for storage at -20 degrees C and subsequent analysis.
      Tissue/blood partition coefficients depend on the amount of triglyceride which
      accumulates in blood from the propofol vehicle; for blood, free of added
      triglyceride, the following coefficients were calculated: brain, 3.23; heart,
      5.94; kidney, 2.46; spleen, 1.86; semimembranosus muscle, > or = 1.61; triceps
      muscle, > or = 1.47. Calculated tissue/water coefficients were 35 times greater.
      There was indirect evidence of extraction of propofol by the lungs.

PMID- 11575348
TI  - Antinociceptive properties of neurosteroids III: experiments with alphadolone
      given intravenously, intraperitoneally, and intragastrically.
AB  - The veterinary neurosteroid anaesthetic Saffan has the same formulation as
      Althesin now withdrawn from human use and is a mixture of two neurosteroids,
      alphadolone, and alphaxalone. The molecular structures of these two pregnanes and
      their properties as i.v. anaesthetics were reported to be similar. Preliminary
      experiments showed that alphadolone caused powerful antinociceptive effects
      without sedation when given i.p. In this study, alphadolone was given to rats
      (weight 100-200 g) i.v., i.p., and intragastrically. I.v. injections of
      alphadolone (25 mg kg(-1)) caused anaesthesia and sedation, whereas i.p. (0.1-100
      mg kg(-1)) and intragastric administration (750 mg kg(-1)) produced no such
      effects. Intragastric alphadolone caused antinociceptive effects assessed with
      the electrical current threshold test (response 2.2 x pre-drug control values)
      without sedation. These effects were reversed at the level of the spinal cord by
      intrathecally-administered bicuculline (10 pmol). We conclude that a metabolite
      of alphadolone acetate produced in the liver leads to antinociceptive effects
      after i.p. and intragastric administration of the parent compound. This
      antinociception involves spinal cord GABA(A) receptors, even though the drug was
      administered via a non-spinal route.

PMID- 11575349
TI  - Hormone replacement therapy (HRT) and anaesthesia.

PMID- 11575350
TI  - Abnormal pupillary activity in a brainstem-dead patient.
AB  - The pupils in brainstem-dead patients are classically fixed and dilated. We
      present a case of a brainstem-dead patient whose pupils displayed persistent
      asynchronous pupillary constriction and dilatation independent of external
      physical stimuli. Central causes for the phenomenon were excluded leaving an
      unexplained peripheral cause as the most likely explanation. Early recognition of
      this phenomenon prevents delay in the diagnosis of brainstem death, lessening to
      some extent the distress for the family, and facilitating earlier organ donation
      and allowing the better use of resources.

PMID- 11575351
TI  - Subdural haematoma after dural puncture headache treated by epidural blood patch.
AB  - Subdural haematoma is a well-documented complication of accidental dural
      puncture, and is thought to be preventable by prompt treatment with an epidural
      blood patch. An accidental dural puncture occurred in a 39-yr-old primagravida
      during the siting of an epidural catheter for pain relief in labour. Twenty hours
      after the puncture, the mother developed a typical postdural puncture headache,
      which increased in severity over the subsequent 24 h. An epidural blood patch was
      performed at 48 h, and this initially relieved the headache. After discharge from
      hospital, and 14 days after the dural puncture, the headache recurred, together
      with expressive dysphasia, poor co-ordination and sensory loss in the right arm.
      A magnetic resonance imaging scan demonstrated a left sided subdural haematoma,
      which was drained successfully with complete recovery.

PMID- 11575352
TI  - Incremental spinal anaesthesia for elective Caesarean section in a patient with
      Eisenmenger's syndrome.
AB  - We describe a new approach to anaesthesia for elective Caesarean section in a
      woman with Eisenmenger's syndrome. Incremental regional anaesthesia was performed
      using a microspinal catheter and haemodynamic monitoring included transthoracic
      bioimpedance cardiography. This approach allowed the disadvantages of general
      anaesthesia and invasive cardiac output monitoring to be avoided.

PMID- 11575353
TI  - Undiagnosed myasthenia gravis unmasked by neuromuscular blockade.
AB  - Myasthenia gravis is an uncommon autoimmune disease resulting in destruction of
      the postsynaptic nicotinic receptors at the neuromuscular junction. We describe a
      43-yr-old, 95 kg patient who presented for elective laparoscopic cholecystectomy.
      She was given vecuronium 10 mg to facilitate tracheal intubation. At the end of
      the procedure the patient could not maintain adequate spontaneous ventilation
      despite administration of two doses of neostigmine 2.5 mg. Subsequent
      investigation led to a diagnosis of myasthenia gravis. We discuss the
      investigation, diagnosis, and subsequent management of such a patient and
      emphasize that tactile estimation of the train-of-four ratio is not a reliable
      indicator of adequate recovery of neuromuscular function.

PMID- 11575354
TI  - Haemodynamic changes during retroperitoneoscopic adrenalectomy for
      phaeochromocytoma.
AB  - Surgical removal of phaeochromocytoma may be accompanied by acute cardiovascular
      changes. We report the haemodynamic changes in seven patients with
      retroperitoneal laparoscopic adrenalectomy for phaeochromocytoma. Transient
      hypertension (systolic pressure (SBP) > 160 mm Hg) was observed in all patients
      during manipulation of the tumour, in two patients during pneumoretroperitoneum
      insufflation, and in one patient during intubation. Small doses of nicardipine
      were sufficient to control these episodes of hypertension. Transient hypotension
      (SBP < 100 mm Hg) was observed in two patients during exsufflation and in one
      patient during repositioning to the lateral position. Our observations suggest
      that this approach provides relative haemodynamic stability, especially during
      pneumoretroperitoneum insufflation.

PMID- 11575355
TI  - Conflicts of interest: are they a problem for anaesthesia journals?

PMID- 11575356
TI  - Skin testing and the anaesthetist.

PMID- 11575358
TI  - Location of anaesthetic monitors.

PMID- 11575357
TI  - Lobectomy for cavitating lung abscess.

PMID- 11575359
TI  - Electromyography and acceleromyography do not measure the same physiological
      event.

PMID- 11575360
TI  - The use of salbutamol aerosol inhaler interferes with anaesthetic agent
      monitoring.

PMID- 11575361
TI  - Researcher, clinician, or teacher?

PMID- 11575362
TI  - Researcher, clinician, or teacher?

PMID- 11575363
TI  - Researcher, clinician, or teacher?

PMID- 11575364
TI  - Researcher, clinician, or teacher?

PMID- 11575365
TI  - Researcher, clinician, or teacher?

PMID- 11575366
TI  - Researcher, clinician, or teacher?

PMID- 11575367
TI  - Missing HIV kits in Pakistan.

PMID- 11575368
TI  - Missing HIV kits in Pakistan.

PMID- 11575369
TI  - Global tobacco control.

PMID- 11575370
TI  - Integrity in Science Database.

PMID- 11575371
TI  - Poisson distribution to assess actinic keratoses in xeroderma pigmentosum.

PMID- 11575372
TI  - Poisson distribution to assess actinic keratoses in xeroderma pigmentosum.

PMID- 11575373
TI  - Outcome in anorexia nervosa.

PMID- 11575374
TI  - Fetal origins hypothesis in India.

PMID- 11575375
TI  - A non-sense mutation and protection from severe malaria.

PMID- 11575376
TI  - A non-sense mutation and protection from severe malaria.

PMID- 11575377
TI  - Effective provision of antenatal   care.

PMID- 11575378
TI  - Countries' health performance.

PMID- 11575379
TI  - It could only happen to a vet.

PMID- 11575380
TI  - Another sniffer dog for the clinic?

PMID- 11575381
TI  - Standard methods to measure HIV drug concentrations.

PMID- 11575382
TI  - Can we characterize the central nervous system actions of alpha2-adrenergic
      agonists?

PMID- 11575383
TI  - Mechanical and electrophysiological effects of thiopental on rat cardiac left
      ventricular papillary muscle.
AB  - Thiopental induces a negative inotropic effect on mammalian heart muscle, where
      it decreases Ca2+ current and Ca2+ release from the sarcoplasmic reticulum and
      reduces K+ currents. We analysed the effects of thiopental on the mechanical and
      electrical activities of rat myocardium, which differ markedly from those of
      other mammals. The effects of thiopental on mechanical parameters and on the
      transmembrane resting (RP) and action (AP) potentials of rat left ventricular
      papillary muscle were investigated. These effects were also studied in the
      presence of atenolol, a beta-blocking agent, and 4-aminopyridine (4-AP), a
      blocker of the transient outward K+ current. Thiopental (3.8 x 10(-6), 3.8 x 10(
      5) and 1.1 x 10(-4) M) induced a dose-dependent positive inotropic effect. This
      positive inotropic effect persisted in the presence of atenolol (1 x 10(-6) M)
      but did not develop in the presence of 1 mM 4-AP; 4-AP had a positive inotropic
      effect but not in the presence of thiopental. Moreover, thiopental (3.8 x 10(-5)
      M) lengthened the plateau and the slow repolarizing phase of the AP, while 1 mM 4
      AP only prolonged the plateau duration. In rat myocardium, the positive inotropic
      effect of thiopental in part mimics that of 4-AP, and in part may be explained by
      the lengthening of the slow repolarizing phase of the AP.

PMID- 11575384
TI  - Lazaroids: efficacy and mechanism of action of the 21-aminosteroids in
      neuroprotection.

PMID- 11575385
TI  - Model-based administration of inhalation anaesthesia. 1. Developing a system
      model.
AB  - This paper is the first of a series of reports on a system model for the
      administration of inhalation anaesthesia. We present the development and basic
      testing of the model. It is a multiple-gas model; it covers fresh-gas flow rates
      from basal to more than total ventilation and includes an actual, not an
      idealized, circle-absorber breathing system featuring a standing bellows
      ventilator. Kinetics of nitrogen, oxygen, carbon dioxide, nitrous oxide, inhaled
      anaesthetic agents and helium are described. Their partial pressures sum to the
      total pressure. Ventilation and cardiac output are treated as continuous, not
      cyclical. The model of the breathing system was empirically matched to the chosen
      one (a GMS absorber and 7850 ventilator (Datex-Ohmeda)). Predictions for the wash
      in of isoflurane and the uptake of desflurane and isoflurane agree well with
      observed data. The results obtained by continuously checking total gas pressures,
      calculating mass balances and simulating the measurement of alveolar space by the
      closed-circuit helium dilution method support the mathematical credibility of the
      model. It thus merits further exploration.

PMID- 11575386
TI  - Pharmacokinetic profile of epidurally administered methylnaltrexone, a novel
      peripheral opioid antagonist in a rabbit model.
AB  - Methylnaltrexone (MNTX) is the first peripheral opioid receptor antagonist used
      in man to treat acute and chronic opiate-mediated side-effects. We describe in a
      rabbit model the pharmacokinetics of epidurally administered MNTX 0.66 mg kg(-1),
      and we tested the hypothesis that epidurally administered MNTX does not penetrate
      the dura into the subarachnoid space. There were minimal concentrations of MNTX
      (40 ng ml(-1)) detected in the CSF at 10 and 20 min and none thereafter in
      comparison with the high serum levels. The serum drug concentration-time profile
      fitted a two-compartment pharmacokinetic model. Further studies are warranted as
      epidurally administered MNTX may have the potential to reverse epidural opioid
      mediated side-effects whilst preserving analgesia.

PMID- 11575387
TI  - Influence of head and neck position on cuff position and oropharyngeal sealing
      pressure with the laryngeal mask airway in children.
AB  - We studied how head and neck position affect the cuff position and oropharyngeal
      sealing pressures of the laryngeal mask airways (LMAs) in children. We studied 39
      non-paralyzed healthy children aged 1.5-8.0 yr, weighing 10.3-27.0 kg, managed
      with size 2 or 2.5 LMAs during elective surgery. Head and neck movements did not
      adversely affect airway patency in 97% of patients. One child developed apparent
      airway obstruction with head and neck flexion, which was relieved in the neutral
      position. Oropharyngeal sealing pressure was significantly greater during neck
      flexion compared with the neutral position (P<0.02). Fibreoptic examination
      revealed that the epiglottis covered a larger area of the LMA aperture during
      neck flexion, compared with the neutral position (P<0.02).

PMID- 11575388
TI  - Waste gas exposure to sevoflurane and nitrous oxide during anaesthesia using the
      oesophageal-tracheal Combitube small adult.
AB  - Exposure to sevoflurane (SEV) and nitrous oxide during ventilation using a
      Combitube (37Fr) small adult (SA) was compared with waste gas exposure using
      conventional endotracheal tubes. Trace concentrations of SEV and nitrous oxide
      were assessed using a direct reading spectrometer during 40 gynaecological
      laparoscopic procedures under general anaesthesia. Measurements were made at the
      patients' mouth and in the anaesthetists' breathing zone. Mean (SD)
      concentrations of SEV and nitrous oxide measured at the patients' mouth were
      comparable in the Combitube SA (SEV 0.6 (0.2) p.p.m.; nitrous oxide 9.7 (8.5)
      p.p.m.) and endotracheal tube group (SEV 1.2 (0.8) p.p.m.; nitrous oxide 17.2
      (10.6) p.p.m.). These values caused comparable contamination of the
      anaesthetists' breathing zone (SEV 0.6 (0.2) p.p.m. and nitrous oxide 4.3 (3.7)
      p.p.m. for the Combitube SA group, compared with SEV 0.5 (0.2) p.p.m. and nitrous
      oxide 4.1 (1.8) p.p.m. for the endotracheal tube group). We conclude that the use
      of the Combitube SA during positive pressure ventilation is not necessarily
      associated with increased waste gas exposure, especially when air conditioning
      and scavenging devices are available.

PMID- 11575389
TI  - Effect of two anaesthetic regimens on airway nitric oxide production in horses.
AB  - There is evidence that halothane inhibits nitric oxide synthase in vitro, but the
      effect of intravenous anaesthetic agents is less clear. This study was undertaken
      to compare the rate of exhaled nitric oxide production (VNO) in spontaneously
      breathing horses anaesthetized with halothane or an intravenous regimen. Seven
      adult horses were studied twice in random order. After premedication with
      romifidine 100 microg kg(-1), anaesthesia was induced with ketamine 2.2 mg kg(-1)
      and maintained with halothane in oxygen (HA) or by an intravenous infusion of
      ketamine, guaiphenesin and romifidine (IV). Inhaled and exhaled nitric oxide (NO)
      concentrations, respiratory minute ventilation (VE), pulmonary artery pressure
      (PPA), fractional inspired oxygen concentration (FIO2), end-tidal carbon dioxide
      concentration (E'CO2), cardiac output (Q) and partial pressures of oxygen and
      carbon dioxide in arterial blood (PaO2, PaCO2) were measured. Exhaled nitric
      oxide production rate was significantly lower (40 min, P<0.01; 60 min, P<0.02)
      during HA [40 min, 1.4 (SD 1.4) pmol l(-1) kg(-1) min(-1); 60 min, 0.7 (0.7) pmol
      l(-1) kg(-1) min(-1)] than during IV [40 min, 9.3 (9.9) pmol l(-1) kg(-1) min(
      1); 60 min, 12.5 (13.3) pmol l(-1) kg(-1) min(-1)). Mean pulmonary artery
      pressure was significantly higher (40 min, P<0.01; 60 min, P<0.001) during HA [40
      min, 5.9 (1.1) kPa; 60 min, 5.9 (0.9) kPa] compared with IV (40 min, 4.4 (0.4)
      kPa; 60 min, 4.4 (0.5) kPa]. NO is reduced in the exhalate of horses
      anaesthetized with halothane compared with an intravenous regimen. It is
      suggested that increased mean pulmonary artery pressure during halothane
      anaesthesia may be linked to the differences in NO production.

PMID- 11575390
TI  - Use of cisatracurium during fast-track cardiac surgery.
AB  - We prospectively studied spontaneous recovery from cisatracurium-induced
      neuromuscular block in 18 patients scheduled for cardiac surgery, and its
      suitability for fast-track cardiac surgery. Neuromuscular block was induced by an
      i.v. bolus (range 0.15-0.3 mg kg(-1)) and maintained by a continuous infusion
      (range 1.1-3.2 microg kg(-1) min(-1)) of cisatracurium until sternal closure. In
      the intensive care unit (ICU), spontaneous recovery was evaluated by the train-of
      four (TOF) ratio measured at the adductor pollicis muscle. The ICU medical staff
      were unaware of the TOF ratios until sedation was stopped. At that time, if the
      TOF ratio was less than 0.9, sedation was recommenced. On arrival in ICU, all
      patients had residual paralysis. The mean time to reaching a TOF ratio of at
      least 0.9 was 102 min (range 74-144 min) after discontinuation of the
      cisatracurium infusion. Fifteen patients (83%) were successfully extubated during
      the first 8 h after stopping the cisatracurium infusion. Only one patient showed
      residual paralysis when sedation was discontinued. These results support the use
      of cisatracurium as a suitable neuromuscular blocking agent for fast-track
      cardiac surgery.

PMID- 11575391
TI  - Successful epidural anaesthesia for Caesarean section in a patient with
      spondyloepiphyseal dysplasia.
AB  - Spondyloepiphyseal dysplasia congenita is a rare genetic entity in which it is
      very important to involve anaesthetists early on to discuss the possible
      anaesthetic complications for both general or regional anaesthesia. A case is
      described of a patient with spondyloepiphyseal dysplasia and multifetal pregnancy
      in which successful epidural anaesthesia for caesarean section was performed.

PMID- 11575392
TI  - Use of remifentanil in a patient with peripartum cardiomyopathy requiring
      Caesarean section.
AB  - We describe a case of a 26 yr old primigravida at 39 weeks' gestation, with a
      diagnosis of peripartum cardiomyopathy, requiring urgent Caesarean section. The
      patient presented in severe heart failure and active labour. A general
      anaesthetic, using a target-controlled infusion of propofol and an intravenous
      infusion of remifentanil, was used to provide stable anaesthesia and analgesia
      for a successful delivery. The unusual diagnosis of peripartum cardiomyopathy and
      the potential benefits of the use of remifentanil in high-risk obstetric surgery
      are discussed.

PMID- 11575393
TI  - Reduction of vasopressor requirement by hydrocortisone administration in a
      patient with cerebral vasospasm.
AB  - A 67-yr-old female received hypertensive, hypervolaemic treatment for cerebral
      vasospasm after severe subarachnoid haemorrhage. After 3 days of continuous
      vasopressor infusion and despite adequate hydration and normal cardiac function,
      the phenylephrine dose had to be increased to obtain the same systolic blood
      pressure. This tachyphylaxis to phenylephrine infusion was probably caused by
      down-regulation of alpha adrenoceptors, and was reversed by giving i.v.
      hydrocortisone.

PMID- 11575394
TI  - Paradoxical changes in bispectral index during nitrous oxide administration.
AB  - I report two patients undergoing open heart surgery, with nitrous oxide and
      isoflurane anaesthesia, for whom bispectral index (BIS) monitoring showed high
      BIS values with nitrous oxide and isoflurane anaesthesia. The BIS decreased
      immediately after nitrous oxide was stopped and increased again after nitrous
      oxide was restarted.

PMID- 11575395
TI  - Therapeutic embolization of an internal mammary artery damaged by placement of a
      central venous catheter.
AB  - We describe the embolization of a left internal mammary artery damaged by left
      internal jugular venous catheterization. Because potentially serious
      complications can occur with a blind approach for central venous catheterization,
      portable ultrasound machines should be used more often to ensure correct
      placement of the catheter.

PMID- 11575396
TI  - Parenteral nutrition: down but not out!

PMID- 11575397
TI  - Parenteral nutrition: down but not out!

PMID- 11575398
TI  - Pre-operative evaluation of the cervical spine in rheumatoid arthritis using
      dynamic magnetic resonance imaging.

PMID- 11575399
TI  - Intravenous opioids reduce airway irritation during induction of anaesthesia with
      desflurane in adults.

PMID- 11575400
TI  - Epidural analgesia during labour.

PMID- 11575401
TI  - Epidural analgesia during labour.

PMID- 11575402
TI  - Low-dose spinal morphine for postoperative analgesia following knee arthroplasty.

PMID- 11575403
TI  - Oral ketoprofen in children--could it have been done differently?

PMID- 11575404
TI  - Huntington's chorea.

PMID- 11575405
TI  - Accidental detection of tracheal bronchus: alternative airway management.

PMID- 11575406
TI  - Model-based administration of inhalation anaesthesia. 2. Exploring the system
      model.
AB  - We explored our model by displaying its new capabilities, testing its sensitivity
      to variations in input data and illustrating its use. Its multiple-gas character
      allows simulation of the mechanisms governing concentration and second gas
      effects. Simulating the volume of a standing bellows makes it possible to test
      algorithms for automated closed-circuit anaesthesia. Using desflurane, the
      model's sensitivity to changes in blood/gas partition coefficient (range 0.42
      0.576), cardiac output and minute ventilation was analysed. The model was very
      sensitive to changes in blood solubility; other results agreed with those
      reported previously. An alveolar isoflurane tension of 1% atm was rapidly
      attained and maintained, even using 0.5 litres min(-1) of fresh gas, when
      isoflurane was 'co-administered' through a vaporizer set to 3.5 vol% and a single
      aliquot (1.25 ml liquid) injected into the expiratory limb. As a result of its
      credibility and capabilities, the model is to be tested in the clinical setting.

PMID- 11575407
TI  - Effects of sevoflurane and propofol on pulmonary shunt fraction during one-lung
      ventilation for thoracic surgery.
AB  - Forty patients requiring one-lung ventilation (OLV) for thoracic surgery were
      randomly assigned to receive propofol (4-6 mg kg(-1) h(-1)) or sevoflurane (1
      MAC) for maintenance of anaesthesia. Three sets of measurements were taken: (i)
      after 30 min of two-lung ventilation (TLV), (ii) after 30 min of one-lung
      ventilation (OLV-1) in the supine position and (iii) during OLV in the lateral
      position (OLV-2) with the chest open and before surgical manipulation of the
      lung. There were no differences between groups in patient characteristics or
      preoperative condition. Increases in shunt fraction during OLV-1 were 17.4% and
      17.2% (P=0.94), those during OLV-2 were 18.3% and 16.5% (P=0.59) for the propofol
      and sevoflurane group, respectively. Cardiac index and other haemodynamic and
      respiratory variables were similar for the two groups. We conclude that
      inhibition of hypoxic pulmonary vasoconstriction by sevoflurane may only account
      for small increases in shunt fraction and that much of the overall shunt fraction
      during OLV has other causes.

PMID- 11575408
TI  - Recovery and neurological examination after remifentanil-desflurane or fentanyl
      desflurane anaesthesia for carotid artery surgery.
AB  - We studied 44 patients undergoing carotid endarterectomy (CEA) to compare
      recovery after general anaesthesia with desflurane supplemented with either
      remifentanil or fentanyl. Remifentanil was infused at 0.1 microg kg(-1) min(-1)
      and desflurane was adjusted at 2 vol% end-tidal. Fentanyl was given as a bolus
      dose of 2 microg kg(-1) before induction and repeated at skin incision;
      desflurane was adjusted as needed. Times for early recovery and response to
      simple neurological tests (digit symbol substitution test (DSST) and Trieger dot
      test (TDT)) were measured 30, 60 and 90 min after operation. Emergence from
      remifentanil-desflurane anaesthesia was significantly quicker than that from
      fentanyl-desflurane anaesthesia: mean times to extubation were 4.1 (SD 1.7) and
      8.2 (4.9) min, respectively; mean times for patients to state their name
      correctly were 6.0 (2.8) and 13.8 (9.0) min, respectively. Patients in the
      remifentanil-desflurane group successfully performed neurological tests
      significantly earlier than those in the fentanyl-desflurane group; for example,
      patients in the former group completed the arm holding test at 7.9 (3.0) min,
      while those in the latter group did this at 20.6 (19.7) min (P < or = 0.01).
      Intermediate recovery was less impaired at 30 min (DSST, TDT) and at 60 min
      (DSST). More rapid awakening and an earlier opportunity for neurological
      examination suggest that remifentanil-desflurane is a suitable alternative to a
      standard fentanyl-based general anaesthetic technique in patients undergoing CEA.

PMID- 11575409
TI  - Sedative, analgesic and cognitive effects of clonidine infusions in humans.
AB  - This placebo-controlled, randomized study evaluated, on separate days, the dose
      response relationship for 1 h infusions of clonidine 1, 2 and 4 microg kg(-1) h(
      1), in eight healthy volunteers aged 22-30 yr. Response end-points included
      sedation (bispectral index, visual analogue scale and observer assessment of
      sedation), analgesia to a cold pressor test, memory (recall of word lists),
      cognitive function (digit symbol substitution test (DSST)), respiratory function
      (respiratory rate, end-tidal carbon dioxide, oxygen saturation) and haemodynamic
      stability (heart rate and mean arterial pressure). Clonidine infusions resulted
      in significant and progressive sedation, but all subjects were easily awoken to
      perform tests and evaluations. Statistically significant analgesia, memory
      impairment and reduced performance on the DSST occurred during 4 microg kg(-1) h(
      1) infusions (resulting in a plasma concentration of 2 ng ml(-1). There were no
      statistically significant changes in cardiorespiratory variables throughout the
      study.

PMID- 11575410
TI  - Comparison of changes in electroencephalographic measures during induction of
      general anaesthesia: influence of the gamma frequency band and electromyogram
      signal.
AB  - Recent research has shown that high-frequency, gamma-band electroencephalographic
      (EEG) oscillations (40-60 Hz) may be an important marker of the conscious state.
      We compared the ability of the bispectral index (BIS) to distinguish the awake
      and anaesthetized states during the induction of general anaesthesia with: (i)
      components of the BIS (BetaRatio, SynchFastSlow); (ii) a new EEG variable--the
      median frequency of the first time derivative of the EEG signal (SE50d); and
      (iii) the SE50d derived from an EEG signal that has had the frequencies above 30
      Hz removed (SE50d(30Hz)). Two groups of subjects were studied: (i) nine
      volunteers undergoing a short propofol infusion until loss of response to verbal
      command, and (ii) 84 patients undergoing routine anaesthesia for a variety of
      surgical procedures. In the volunteer group, the changes in the BetaRatio and
      SE50d were comparable with changes in the BIS. The changes in the SE50d(30Hz)
      were less consistent. In the patient group, the BIS components were equivalent to
      the BIS in separating the awake from the surgically anaesthetized states (area
      under receiver operating curve: BIS 0.95, SE50d 0.95, BetaRatio 0.96). Using the
      submental electromyogram (EMG) signal to estimate the frontalis EMG (30-47 Hz)
      signal, the changes in EMG signal were, on average, about one-tenth the magnitude
      of the EEG. We conclude that: (i) there exist simpler derived EEG variables that
      are similar in accuracy to the BIS; (ii) it is important to avoid filtering out
      the EEG frequencies above 30 Hz; and (iii) in most patients the confounding
      effects of the frontalis EMG on the EEG are minimal.

PMID- 11575411
TI  - Effects of different concentrations of sevoflurane and desflurane on subcortical
      somatosensory evoked responses in anaesthetized, non-stimulated patients.
AB  - Twenty-four patients were recruited and given either sevoflurane or desflurane as
      their sole anaesthetic. Each patient was given sequentially increasing or
      decreasing doses at 0.5 MAC intervals, and the median nerve somatosensory evoked
      response recorded after an equilibration at each concentration. The N20-P25 and
      P25-N35 amplitudes decreased with increasing agent concentration. However, for
      both agents the P15-N20 amplitude response was quadratic in shape. The peak
      inflection points were at 3.2% for sevoflurane and 4.9% for desflurane. There
      were no differences between the ascending and descending groups. This increase in
      activity in the midbrain at 'surgical' end-tidal anaesthetic concentrations
      suggests more complex neuroelectrical responses to anaesthesia than simple global
      suppression.

PMID- 11575412
TI  - Pre-existing cognitive impairment as a factor influencing outcome after cardiac
      surgery.
AB  - Conventional methodology to investigate cognitive impairment after coronary
      artery bypass graft (CABG) surgery leaves unclear the potential for pre-existing
      cognitive deficits to influence outcome. Individuals with pre-existing deficits
      may be more vulnerable to the effects of CABG, hence biasing the results of a
      typical prospective trial if account is not taken of their state. The present
      study examined the effect of pre-existing cognitive impairment upon cognitive
      outcome in 81 patients undergoing CABG. Patients performed the Stroop
      Neuropsychological Screening Test and other psychometric assessments prior to and
      at 6 days and 6 months after CABG. Those with pre-existing cognitive deficits
      were significantly more likely to display impairment at 6-day and 6-month follow
      ups than were those without pre-existing deficits. Greater age and lower pre
      morbid intelligence were also significant predictors of post-CABG deficit,
      confirming earlier findings. The results imply both that pre-existing cognitive
      impairments may render patients more vulnerable to post-operative deficits and
      that, in the absence of such pre-existing impairments, CABG surgery does not
      inevitably lead to later deficits. The study also replicated previous findings
      showing a similar influence of pre-existing depression upon emotional state after
      CABG. Overall, the results confirm the importance both of a patient's pre
      existing cognitive and emotional states, and the methodology to assess them, in
      influencing outcome after cardiac surgery and the conclusions to be drawn as to
      the supposed adverse effects of the procedure.

PMID- 11575413
TI  - Fast-track cardiac anaesthesia in the elderly: effect of two different
      anaesthetic techniques on mental recovery.
AB  - Elderly patients may be considered for 'fast-track' cardiac anaesthesia, but can
      suffer psychological complications and slow recovery of mental function after
      surgery, which can interfere with recovery. Reduced metabolism and changed
      distribution of anaesthetic and sedative agents can cause poor recovery. We made
      a prospective randomized comparison of mental function, haemodynamic stability
      and extubation and discharge times in elderly patients (65-79 yr) receiving two
      premedication, anaesthetic and sedative techniques. Patients received either
      propofol (n=39) (fentanyl 10-15 microg kg(-1) and propofol 2-6 mg kg(-1)
      intraoperatively and a propofol infusion for 3 h postoperatively) or
      premedication with lorazepam followed by midazolam for anaesthesia (n=39)
      (fentanyl 10-15 microg kg(-1) and midazolam 0.05-0.075 mg kg(-1) intraoperatively
      and a midazolam infusion for 3 h postoperatively). Impairment of mental function
      was noted in 41% of patients in the propofol group and 83% in the lorazepam and
      midazolam group (P=0.001) 18 h after extubation. Patients in the propofol group
      were extubated earlier [1.4 (SD 0.6) vs 1.9 (0.8) h, P=0.02]; and reached
      standard intensive care unit discharge criteria [7.6 (4.6) vs 14.2 (13) h,
      P=0.02] and hospital discharge criteria [4.3 (1.0) vs 4.9 (1.1) days, P=0.04)
      sooner than patients in the lorazepam and midazolam group, but actual discharge
      times did not differ between the groups. Haemodynamic values were stable in both
      groups.

PMID- 11575414
TI  - Intrathecal midazolam increases the analgesic effects of spinal blockade with
      bupivacaine in patients undergoing haemorrhoidectomy.
AB  - In the present double-blind study we aimed to evaluate the postoperative
      analgesic effects of intrathecal midazolam with bupivacaine following
      haemorrhoidectomy. Forty-five patients were randomly allocated to one of three
      groups: the control group received 1 ml of 0.5% heavy bupivacaine plus 0.2 ml of
      0.9% saline intrathecally, group BM1 received 1 ml of 0.5% bupivacaine plus 0.2
      ml of 0.5% preservative-free midazolam and group BM2 received 1 ml of 0.5%
      bupivacaine plus 0.4 ml of 0.5% midazolam. Time to first analgesia was
      significantly greater in the midazolam groups than in the placebo and
      significantly less in the BM1 group than in the BM2 group.

PMID- 11575415
TI  - Comparison of two neurostimulation techniques for axillary brachial plexus
      blockade.
AB  - This prospective, randomized, double-blind study compared two techniques of
      axillary brachial plexus block using a peripheral nerve stimulator. Both groups
      received initial musculocutaneous nerve block followed by either a single
      injection on median nerve stimulation (group 1) or a double injection divided
      between median and radial nerves (group 2). All 60 patients received a total of
      30 ml of lidocaine 15 mg/ml with epinephrine 5 microg/ml. Complete sensory
      blockade of all six peripheral nerves occurred in 53% and 97% of patients in
      groups 1 and 2, respectively (P<0.001), with a more rapid onset of blockade
      occurring in group 2 patients (P<0.001). Complete motor blockade was evident in
      30% and 83% of patients in groups 1 and 2, respectively (P<0.001).

PMID- 11575416
TI  - Dexamethasone is a cost-effective alternative to ondansetron in preventing PONV
      after paediatric strabismus repair.
AB  - This study evaluated the antiemetic efficacy, cost-effectiveness and clinical
      utility of prophylactic ondansetron and dexamethasone compared with placebo in
      the prevention of postoperative nausea and vomiting (PONV) in 135 children (2-15
      yr, ASA I-II) undergoing strabismus repair. After induction with halothane and
      nitrous oxide in oxygen or i.v. thiopental, the children received i.v.
      dexamethasone 1 mg kg(-1) to a maximum of 25 mg, ondansetron 100 microg kg(-1) to
      a maximum of 4 mg or placebo (n=45). Episodes of PONV were recorded for the first
      24 h after the operation. True outcome measures (parental satisfaction score,
      duration of stay in the postanaesthesia care unit and fast tracking time),
      therapeutic outcome measures (number needed to prevent (NNTP) PONV) and the cost
      to benefit a child with each drug were analysed. The incidence and severity of
      PONV in the first 24 h were significantly less in the dexamethasone and
      ondansetron groups than in the placebo group (P<0.05). The incidence (P=0.04) and
      severity (P=0.03) of PONV at the 6-24 h epoch were significantly less in the
      dexamethasone group than in the ondansetron group. Recovery time (P=0.07), fast
      tracking time (P=0.6), parental satisfaction scores (P=0.08) and NNTP PONV were
      comparable (NNTP=2) in both the ondansetron and the dexamethasone group. The cost
      to benefit a child with dexamethasone was approximately 22 times less than that
      of ondansetron.

PMID- 11575417
TI  - Comparison of effects of remifentanil and alfentanil on cardiovascular response
      to tracheal intubation in hypertensive patients.
AB  - In a randomized double-blind study, we compared the effect of remifentanil and
      alfentanil on the cardiovascular response to laryngoscopy and tracheal intubation
      in patients on long-term treatment for hypertension. Forty ASA II-III patients
      were allocated to receive (i) remifentanil 0.5 microg kg(-1) followed by an
      infusion of 0.1 microg kg min(-1) or (ii) alfentanil 10 microg kg(-1) followed by
      an infusion of saline; all patients received glycopyrrolate 200 microg before the
      study drug. Anaesthesia was induced with propofol and rocuronium and maintained
      with 1% isoflurane and 66% nitrous oxide in oxygen. Laryngoscopy and tracheal
      intubation were performed after establishment of neuromuscular block. Arterial
      pressure and heart rate (HR) were measured non-invasively at 1 min intervals from
      3 min before induction until 5 min after intubation. Systolic (SAP), diastolic
      and mean arterial pressure decreased significantly after induction in both groups
      (P<0.05). Maximum increases in mean SAP after laryngoscopy and intubation were 35
      and 41 mm Hg in the remifentanil and alfentanil groups, respectively. After
      intubation, arterial pressure did not increase above baseline values in either
      group. HR remained stable after induction of anaesthesia, but increased above
      baseline values after intubation. Mean maximum HR was 87 beats min(-1) for the
      remifentanil group (12 beats min(-1) above baseline; P=0.065) and 89 beats min(
      1) for the alfentanil group (15 beats min(-1) above baseline; P<0.05). There were
      no significant differences between groups in HR or arterial pressure at any time.
      There were no incidences of bradycardia. Seven patients in the remifentanil group
      and four in the alfentanil group received ephedrine for hypotension (i.e. SAP<100
      mm Hg).

PMID- 11575418
TI  - Comparison of coagulation and blood loss during anaesthesia with inhaled
      isoflurane or intravenous propofol.
AB  - Propofol has been reported to affect blood coagulation. This prospective,
      randomized study compared coagulation and blood loss during anaesthetic
      maintenance with target-controlled intravenous propofol infusion vs. inhaled
      isoflurane. Thirty-eight ASA I-III patients undergoing head and neck surgery were
      allocated randomly to receive either inhaled isoflurane at end-tidal
      concentration 1-1.5% (group I, n=20) or target-controlled infusion (TCI) of
      propofol at target concentration 2-5 microg ml(-1) (group P, n=18).
      Thrombelastography on recalcified whole blood was performed pre-induction, and at
      15, 30, 60, 90, 120 min post-induction and 30 min after anaesthesia in both
      groups. Blood loss was estimated from weighing swabs and the volume in suction
      bottles. Induced hypotension was not used, and perioperative body temperature was
      similar between groups. There were no significant differences in
      thrombelastographic coagulation (R-time, K-time, maximum amplitude and angle) or
      fibrinolytic variables (lysis index at 30 and 60 min) at all times between
      groups. Total blood loss was also not significantly different (median group I:
      350 ml, range 20-1200 ml; group P: 200 ml, range 50-800 ml). Shortening of R-time
      and widening of angle developed over time in both groups (P<0.05 groups I and P,
      repeated measures ANOVA). We conclude that maintenance of anaesthesia with
      propofol TCI at 2-5 microg ml(-1) does not cause detectable coagulation changes
      on thrombelastography nor increase surgical blood loss when compared to inhaled
      isoflurane.

PMID- 11575419
TI  - Decontamination of laryngoscopes in The Netherlands.
AB  - In this study the decontamination procedures of laryngoscopes in Dutch hospitals
      are described, based on a structured telephone questionnaire. There were
      substantial differences between decontamination procedures in Dutch hospitals and
      the standards of the APIC (Association of Professionals in Infection Control and
      Epidemiology), CDC (Centers of Disease Control) and ASA (American Society of
      Anesthesiology) were met in full in 19.4% of the hospitals. The standards of
      manual decontamination, used in 78% of the 139 hospitals, were particularly
      disappointing; manual cleaning was considered inadequate in 22.9% of these
      hospitals and manual disinfection did not meet the standards of the APIC, CDC or
      ASA in any of these hospitals. Decontamination by instrument cleaning machines as
      a standard procedure was used in 30 (22%) hospitals. In three of these hospitals
      the blades were subsequently sterilized. We suggest adherence to the infection
      control guidelines of the CDC, APIC and ASA, until the safety of less
      conservative infection control practices are demonstrated.

PMID- 11575420
TI  - Autophagic cell death and its execution by lysosomal cathepsins.
AB  - In the last decade, the molecular mechanisms of apoptosis, a major type of active
      cell death (type I cell death) have largely been clarified in mammalian cells.
      Particularly, the caspase family of proteinases has been shown to play crucial
      roles in the execution of apoptosis. Differing from apoptosis, type II cell death
      is known to be associated with autophagosomes/autolysosomes and appear in the
      developing nervous system (CLARKE, 1990). We have previously shown that delayed
      neuronal death occurring in the CA1 pyramidal layer of the gerbil hippocampus
      after brief forebrain ischemia is apoptotic in nature and
      autophagosomes/autolysosomes abundantly appear in the neurons before DNA
      fragmentation. To further understand the roles of autophagosomes/autolysosomes in
      active cell death, we examined the apoptosis of PC12 cells using morphological
      and biochemical techniques. PC12 cells are known to undergo apoptosis when
      cultured in the absence of serum. In such an environment, the mitochondrial
      pathway of apoptosis is activated; cytochrome c is released from mitochondria,
      and caspase-9/caspase-3 are activated. We have first examined morphological
      features of PC12 cells during the apoptotic process following serum deprivation,
      and found that autophagy is induced from the early stage of the process in the
      cells before typical nuclear changes. When autophagy is inhibited in the cells by
      3-methyladenine, an autophagy inhibitor, they are largely protected from
      apoptosis. In relation to the induction of autophagy in PC12 cells following
      serum deprivation, immunoreactivity, protein amounts, and the proteolytic
      activity of lysosomal proteinases, particularly cathepsins B and D, are all
      greatly altered; those of cathepsin B drastically decrease in the cells from the
      early stage of serum-deprived cultures, whereas those of cathepsin D increase.
      Moreover, PC12 cells overexpressing cathepsin D undergo apoptosis more rapidly in
      serum-deprived cultures than wild-type cells, whereas those overexpressing
      cathepsin B increase the viability. These lines of evidence suggest that
      autophagy is involved in PC12 cell death following serum deprivation, this type
      of cell death being regulated by lysosomal proteinases, cathepsins B and D,
      downstream autophagy.

PMID- 11575421
TI  - Formation of unique vacuoles in tenotomized rat soleus muscle fibers.
AB  - The formation of unique vacuoles in tenotomized rat soleus muscle fibers was
      examined by light and electron microscopy. After tenotomy at both proximal and
      distal tendons, virtually all muscle fibers underwent characteristic degenerative
      changes with a disorganization of myofibrils called the central core lesion, but
      eventually recovered. At 3 days after tenotomy, some muscle fibers showed small
      vacuoles in the sarcoplasm of the end segments, which were larger in diameter and
      paler in staining than those of the control fibers in light microscopy. At 5
      days, more fibers formed larger vacuoles together with the extensive
      disorganization of myofibrils. Such vacuole formation was more conspicuous in the
      distal end than in the proximal end. At 1 week the myofibrillar disorganization
      was most extensive in the central areas, and vacuoles were considerably enlarged
      in some fibers to occupy most of the sarcoplasm near the fiber ends. Vacuoles
      decreased in number and size with time and could rarely be seen at 4 weeks
      postoperative. In thin-section electron microscopy, the early forms of vacuoles
      were often connected with the T-system tubules. The limiting membrane of such
      vacuoles possessed many caveolae, some of which appeared to be continuous with
      the T-system networks. The vacuole membrane was closely associated with the
      sarcoplasmic reticulum to form dyadic connections. In later stages, the vacuole
      membrane was lined in part with the basal lamina. From these findings, it can be
      concluded that the vacuoles are sarcolemmal in nature and derived from the T
      system. The significances of the vacuole formation are discussed with special
      reference to the mechanism and fate of the vacuoles and their clinical
      implications.

PMID- 11575422
TI  - Morphological and histochemical changes in the secretory granules of mucous cells
      in the early postnatal mouse parotid gland.
AB  - It has previously been known that the developing parotid glands in humans and
      rats contain mucous cells in their terminal clusters and acini, but these cells
      disappear within a short period of time. Using rat parotid glands, IKEDA and
      AIYAMA (1997, 1999) suggested that the mucous cells might change into serous
      cells in the early postnatal period, but it is uncertain whether mucous cells
      appear only in the developing parotid gland of a few species such as humans and
      rats, or whether the cell transformation actually occurs. To clarify these
      points, the present study investigated the developing mouse parotid glands. Light
      microscopy showed cells with secretory granules that stained extensively with PAS
      and alcian blue in the terminal clusters of a 1-day-old mouse parotid gland.
      Mucous cell numbers in the terminal clusters and the acini reached a peak on day
      5 and decreased on day 7. By day 10, the mucous cells had disappeared altogether.
      Thus, the presence of mucous cells in the developing mouse parotid gland was
      confirmed. Electron microscopy showed granules of low-electron-density and
      bipartite granules in the mucous cells. Bipartite granules and highly electron
      dense granules sometimes co-existed in a single cell. Immuno-electron microscopy
      revealed a positive reaction for amylase to the low-electron-density granules and
      the low-electron-density portions of the bipartite granules, in addition to the
      highly electron-dense granules and the electrondense cores of the bipartite
      granules. No mucous cells with nuclei displaying characteristics of apoptosis
      were recognizable. Lectin histochemistry both at the light and electron
      microscopic levels showed that the secretory granules in the mouse parotid gland
      mucous cells had sugar residues similar to those of the mature serous granules.
      These findings demonstrate that mucous cells appear in the early postnatal mouse
      parotid gland, and that almost all of these cells may be converted into serous
      cells.

PMID- 11575423
TI  - Target specific organization and neuron types of the dog pelvic ganglia: a
      retrograde-tracing and immunohistochemical study.
AB  - The major pelvic ganglion in both the rat and guinea pig has been extensively
      studied because of its anatomical simplicity. To clarify the target specific
      neural pathway in the diffusely distributed pelvic ganglia of larger animals, the
      pelvic plexus of the female dog was investigated by retrograde tracing and
      immunohistochemistry. The whole mount staining of the pelvic plexus with
      acetylcholinesterase histochemistry revealed 70-100 ganglia of varying sizes.
      Neurons retrogradely labeled from the rectum were mainly found in ganglia located
      in the dorso-caudal part of the plexus. The majority of these were non
      catecholaminergic, immunoreactive for either calbindin (Calb) or neuropeptide Y
      (NPY), and characteristically associated with baskets of enkephalin (ENK)
      immunoreactive varicose fibers. Neurons projecting to the utero-vaginal walls
      were distributed in ganglia located in the ventro-caudal part of the plexus.
      These mainly consisted of two major neuron groups: catecholaminergic Calb
      immunoreactive neurons, and non-catecholaminergic neurons containing nitric oxide
      synthase (NOS) and/or vasoactive intestinal peptide (VIP), which were
      preferentially associated with a network of ENK-immunoreactive varicose fibers.
      Neurons retrogradely labeled from the urinary bladder mainly occurred in ganglia
      located around the junction between the ureter and the bladder. These consisted
      of catecholaminergic Calb neurons and noncatecholaminergic neurons containing
      Calb or NOS. Only a few ENK-immunoreactive fibers were found within the clusters
      of catecholaminergic neurons. These results indicate that organ specific neurons
      are located in separate ganglia and have both a distinctive composition of neuron
      types as well as different innervation by preganglionic fibers.

PMID- 11575424
TI  - Locations and innervation of cell bodies of sympathetic neurons projecting to the
      gastrointestinal tract in the rat.
AB  - The locations of cell bodies of sympathetic neurons projecting to the stomach,
      the duodenum, the ileum, the colon, the spleen and the pancreas have been studied
      using retrograde tracing. Projections arose from both pre- and paravertebral
      ganglia. In the rat, the prevertebral ganglia are the paired coeliac ganglia
      lying caudo-lateral to the root of the coeliac artery, paired splanchnic ganglia
      in the abdominal segments of the greater splanchnic nerves, unpaired superior
      mesenteric and inter-renal ganglia and the inferior mesenteric ganglia. The
      projections from the prevertebral sympathetic ganglia to the different parts of
      the gut were organised somatotopically. The most rostral ganglia (splanchnic,
      coeliac, and superior mesenteric ganglia) contained neurons innervating all
      regions of the gastrointestinal tract, the pancreas and the spleen. The inter
      renal and inferior mesenteric ganglia, located more caudally, contained neurons
      innervating the distal part of the gut (distal ileum and colon). The innervation
      of the spleen and the pancreas came from the closest ganglia (sympathetic chains,
      splanchnic and coeliac ganglia). This organotopic organisation was not found in
      the sympathetic chain ganglia; the innervation of all organs came predominantly
      from the lower part of the thoracic chains. A large proportion of the
      retrogradely labelled nerve cells in the splanchnic ganglia received nitric oxide
      synthase immunoreactive innervation probably from the spinal cord. In the other
      prevertebral ganglia, most of the neurons received nitric oxide synthase
      immunoreactive innervation and/or bombesin immunoreactive innervation. This leads
      to the conclusion that, in these ganglia, many neurons receive projections from
      the gastrointestinal tract in addition to the spinal cord.

PMID- 11575425
TI  - Distribution of amylin-immunoreactive neurons in the monkey hypothalamus and
      their relationships with the histaminergic system.
AB  - Amylin (AMY) is a 37 amino acid peptide of pancreatic origin that has been
      localized in peripheral and central nervous structures. Both peripheral and
      central injection of the peptide causes various effects, including anorectic
      behavior in rats. Prompted by previous reports showing that the anorectic effect
      of AMY is mediated by histamine release, we immunohistochemically investigated
      possible relationships between these two systems at the light microscopical
      level. Monkey (Macaca fuscata japonica) hypothalamus specimens were submitted to
      immunohistochemical double staining procedures using AMY and histidine
      decarboxylase (HDC) antisera. AMY-immunoreactive neurons were found widely
      distributed in several nuclei of the monkey hypothalamus including the
      supraoptic, paraventricular, perifornical, periventricular, ventromedial,
      arcuate, and tuberomammillary nuclei. We detected AMY-immunoreactive nerve fibers
      throughout the hypothalamus, the median eminence and hypothalamus
      neurohypophysial tract. Although AMY- and HDC-immunoreactive neuronal cell bodies
      occupied distinct hypothalamic zones, many HDC-immunoreactive cell bodies and
      dendrites, particularly those in the periventricular, arcuate, and rostral
      tuberomammillary regions, were surrounded by numerous AMY-immunoreactive nerve
      fiber varicosities. These findings demonstrate for the first time the presence of
      a discrete number of AMY-immunoreactive neurons in the monkey hypothalamus and
      add morphological support to the experimental data demonstrating that AMY
      probably exerts its influence on food intake via the histaminergic system.

PMID- 11575426
TI  - Seromucous cells in human sublingual glands: examination by immunocytochemistry
      of lysozyme.
AB  - This study examined the occurrence and morphological features of serous-type
      cells in human sublingual gland, using immunocytochemistry for lysozyme. Lysozyme
      positive cells usually formed demilunes and occasionally their own acini. They
      were also found among cells of an intercalated duct and in its immature acinus
      consisting of a small number of secretory cells. All these serous cells could be
      classified as seromucous cells because they simultaneously revealed reactivity
      for mucus, i.e., a periodic acid-Schiff (PAS) and a periodic acid
      thiocarbohydrazide-silver proteinate (PA-TCHSP) reaction under the light- and
      electron-microscope, respectively. Immunogold labeling of lysozyme in the
      seromucous cells was distributed on variously sized secretory granules. These
      usually possessed a single electron-dense spherule in an electron-lucent matrix,
      while granules of a homogenous structure were also present. Lysozyme-positive
      cells filled with large, lucent secretory granules could hardly be
      morphologically distinguished from the lysozyme-negative mucous cells; they
      corresponded to "intermediate" cells designated under the light microscope. All
      "immature" secretory cells with only a few secretory granules were also lysozyme
      positive seromucous cells. The present study demonstrated that the seromucous
      cells in the human sublingual glands conform closely with those in the human
      labial glands (MIYAZAKI et. al., 1998).

PMID- 11575427
TI  - The intensely positively charged perineuronal net in the adult rat brain, with
      special reference to its reactions to oxine, chondroitinase ABC, hyaluronidase
      and collagenase.
AB  - Light microscopic observations of healthy adult rat brain sections stained with
      anionic iron colloid indicated that 5-10% of neurons in the hippocampal subiculum
      and all neurons in the medial cerebellar nucleus possessed an intensely
      positively charged perineuronal net. This net was demonstrated to react to oxine,
      and therefore suggested to consist of guanidino compounds. It was further shown
      that the intensely positively charged perineuronal net, in accordance with the
      intensely negatively charged perineuronal net of proteoglycans, was digested by
      chondroitinase ABC, hyaluronidase, and collagenase, but not by endo-alphaN
      acetylgalactosaminidase. This finding suggested that the former positively
      charged net might be linked to the latter negatively charged one.

PMID- 11575428
TI  - Cellular distribution of napsin (kidney-derived aspartic protease-like protein,
      KAP) mRNA in the kidney, lung and lymphatic organs of adult and developing mice.
AB  - Kidney-derived aspartic protease-like protein (KAP), initially identified in the
      mouse kidney, is a novel aspartic protease exclusively expressed in the lung and
      spleen as well as the kidney. Its orthologues have been identified in the human
      and rat, and termed napsin. We performed in situ hybridization analysis to
      determine the cellular expression of napsin mRNA in the kidney, lung, and
      lymphatic organs of adult mice and to demonstrate, for the first time, its
      expression patterns in ontogeny. In the adult mouse kidney, extremely intense
      signals for napsin mRNA were observed in the proximal straight and convoluted
      tubules, in agreement with a previous study. The first signals for napsin mRNA
      during nephrogenesis occurred selectively in mesonephric tubules at embryonic day
      13, and in metanephric tubules from embryonic day 14. In the lung, a distribution
      restricted to type II alveolar cells or their precursors was found from embryonic
      day 15, at the onset of type II cell differentiation, to the adult stage. In the
      spleen, the mRNA was expressed in lymph nodules of the white pulp and the
      marginal zone-namely, B-lymphocyte-rich regions from postnatal day 0 to adult.
      The lymph node and Peyer's patch displayed similar expression patterns, but T
      cell-dependent areas in these organs and the thymus lacked such signals. These
      findings suggest that mouse napsin possesses crucial functional roles not only in
      the kidney but also in the lung and lymphatic tissues, even during fetal stages.

PMID- 11575429
TI  - Expression and immunolocalization of AQP6 in intercalated cells of the rat kidney
      collecting duct.
AB  - The expression and localization of AQP6 were examined in rat kidneys. In the
      kidney compartments, the expression was more intense in the outer medulla than in
      the cortex or inner medulla, and was negative in the glomerulus. During
      development, the AQP6 mRNA expression in the kidney was not detected in the
      fetus, but was recognized at birth, increased gradually by 4 weeks of age, and
      was unchanged thereafter. In situ hybridization demonstrated significant signals
      for AQP6 mRNA along the outer and inner medullary collecting ducts. Since the
      localization of the AQP6 mRNA-expressing cells was comparable to that of
      immunoreactive H+ ATPase-bearing cells in the collecting duct, they were
      identified as intercalated cells. No AQP6 mRNA signals were recognizable in other
      cells in the kidneys, including glomerular cells. No glomerular expression of
      AQP6 mRNA was confirmed by RT-PCR using total RNA extracted from the glomeruli.
      Immunohistochemistry using an antibody raised against recombinant rat AQP6
      protein could localize the immunoreactivity in a population of collecting duct
      cells. Serial section observations indicated that the AQP6-immunoreactive cells
      corresponded to H+ ATPase bearing intercalated cells.

PMID- 11575430
TI  - A combined SEM and TEM study on the basal labyrinth of the collecting duct in the
      rat kidney.
AB  - The three-dimensional ultrastructure of principal cells in the rat renal
      collecting duct was studied by scanning electron microscopy (SEM) using the NaOH
      digestion technique and the aldehyde prefixosmium-DMSO-osmium method, as well as
      by transmission electron microscopy (TEM). Special reference was given to the
      basal labyrinth of the cells and its numerous ruffles and infoldings of the basal
      plasma membrane. Observations showed that, as the collecting duct descends from
      the cortical collecting duct (CCD) to the terminal portion of the inner medullary
      collecting duct (t-IMCD), the pattern of the labyrinth gradually simplified and
      the ruffles grew thinner. In the CCD, the labyrinth was conspicuously complicated
      in structure, being formed of tightly arranged ruffles of uniform shape and
      thickness (70 nm). From the outer medullary collecting duct (OMCD) to the initial
      portion of inner medullary collecting duct (i-IMCD), the labyrinth became less
      complicated due to the mingling of wide flattened ruffles. Also, the basal
      infoldings were reduced in depth (from 700 nm in CCD to 500-600 nm in i-IMCD). In
      the t-IMCD, the labyrinth was rudimental, and instead presented small grooves
      (300 nm in depth) which corresponded to indentions of the basal plasma membrane.
      The regional simplification of the labyrinth was accompanied by morphological
      changes in mitochondria suggesting their functional decline: the electron density
      and number of cristae were reduced, these being changed in shape from plate-like
      to vesicular. These morphological data readily account for the potential for
      active transport by the collecting duct, which is highest in the CCD and is
      decreased towards the t-IMCD, and which may function merely as an excretory duct
      of urine from the papilla. The present study three-dimensionally demonstrates
      fine-structural heterogeneity in different segments of the collecting duct of the
      rat kidney.

PMID- 11575431
TI  - Regeneration of liver with marked fatty change following partial hepatectomy in
      rats.
AB  - Resection of liver for primary and metastatic tumors and living donor liver
      transplantation has become a common clinical practice. The success of recovery
      depends on the regeneration and functions of the remnant liver. However,
      information on the regenerative potential of liver with steatosis and
      steatohepatitis, a common clinical problem in this country, is incomplete.
      Therefore, we evaluated regeneration after two-thirds partial hepatectomy (PH) in
      male F-344 rats with marked steatosis and mild steatohepatitis induced by feeding
      choline-deficient diet. Choline-deficient rats and control rats were killed at
      24, 36, 48, 72, and 96 h after PH. Liver regeneration was determined by measuring
      mitotic activity and bromodeoxyuridine (BrdU) labeling in hepatocytes. Livers of
      rats maintained on the choline-deficient diet showed marked steatosis and mild
      steatohepatitis. In these animals the levels of serum and liver triacylglycerols
      (TG) were low and very high, respectively, when compared to controls. In control
      rats mitotic and BrdU labeling indices were maximal at 24 h followed by a rapid
      decline, whereas in choline-deficient rats both these indices increased
      significantly at 36 h and decreased gradually over the next 60 h. By 96 h the
      size of livers in both groups was comparable. The results of this study indicate
      that regeneration in the liver of rats with marked steatosis is not impaired.

PMID- 11575432
TI  - Role of tube design and selection in occurrence of gastric lesser curvature
      ulceration by percutaneous gastrostomy tubes: an issue for adult patients?

PMID- 11575433
TI  - Does Helicobacter pylori gastritis affect motor function of proximal stomach in
      dyspeptic patients?
AB  - The role of Helicobacter pylori infection in proximal gastric motor function and
      its relation to symptoms in patients with functional dyspepsia is still unclear.
      We prospectively studied 26 patients with dyspepsia, no structural abnormalities
      found during endoscopy and biopsy-proven Helicobacter pylori-positive gastritis
      before and three months after Helicobacter pylori treatment. We used an 11-item
      score list to evaluate symptoms, gastric biopsies for histology, and a gastric
      barostat (isobaric inflation-deflation) for proximal gastric motility. Minimal
      distending pressure (MDP), mean gastric volume at operating pressure, AUC of
      inflation-deflation cycles, and hysteresis (difference in AUC during inflation
      and AUC during deflation) were calculated. After three months, Helicobacter
      pylori was eradicated in 96% of patients. MDP, mean gastric volume at operating
      pressure, gastric compliance, and hysteresis did not change significantly.
      Aggregate symptom score as well as histology scores in antrum and corpus
      decreased significantly. Reduction in postprandial pain correlated with a change
      in hysteresis (r = 0.567, P < 0.01), but other symptoms did not. Reduction of
      corpus inflammatory activity correlated with changes in hysteresis (r = 0.604, p
      < 0.005), suggesting that the stomach attains it original shape faster when
      inflammation is reduced. These observations suggest that inflammatory changes or
      release of inflammatory substances associated with Helicobacter pylori infection
      may influence proximal gastric motor characteristics.

PMID- 11575434
TI  - Applied potential tomography in liquid gastric emptying measurement: design,
      assembling, calibration, and clinical application.
AB  - The present study aimed to validate the accuracy of a homemade applied potential
      tomography (APT) apparatus for liquid gastric emptying (GE). Twelve electrodes
      were placed in a circular array around the subjects. Ten electrodes in a rotated
      order recorded electrical current delivered from a driving pair of electrodes.
      Based on tomography, averaged signals of changed resistivity were constructed to
      display area changes. Six beakers were respectively placed into a saline-filled
      Perspex tank to measure their cross-sections. True beaker cross-sections are
      2.01, 15.9, 18.8, 30.19, 38.48, and 63.61 cm2, respectively, whereas APT
      generated cross-sections were 7.9 +/- 2.9, 16.7 +/- 3.3, 22.4 +/- 4.9, 28 +/-
      4.8, 48.7 +/- 7.6, 67 +/- 6.1 cm2, respectively (r = 0.98, P < 0.001). Twenty
      four healthy males ingested 500-ml test solution to assess GE using both APT and
      scintigraphy. Only 20 (83.3%) subjects had a successful measurement. The APT half
      emptying time was 15.6 +/- 4.8 min, whereas scintigraphy was 21.9 +/- 6.3 min (r
      = 0.67, P < 0.01). In conclusion, our APT apparatus is a simple, noninvasive, and
      inexpensive way to assess liquid GE. Its clinical usefulness is confirmed using
      both phantom and human models.

PMID- 11575435
TI  - Postcibal gastric emptying of pancreatin pellets: effects of dose and meal oil.
AB  - To treat pancreatic exocrine insufficiency, physicians often prescribe
      enterically coated pellets of pancreatin to be taken with meals. The pellets are
      only partially effective in correcting the digestion and absorption of fat. We
      sought to determine in normal subjects whether emptying of pellets from the
      postcibal stomach was dose-related and whether the gastric emptying of lipophilic
      Creon-20 or Pancrease was altered by the presence or the absence of oil in a
      meal. Gastric emptying of pellets surface-labeled with 113mIn or 99mTc was
      followed with a gamma camera for 300 min after isocaloric meals. From our
      observations, we concluded that gastric emptying of 0.28-1.12 g of 1-mm or 2-mm
      pellets was dose-related (P < 0.01) and emptying of neither Creon-20 nor
      Pancrease was much affected by oil in the meal.

PMID- 11575436
TI  - Differential effects of nucleoside analogs on oxidative phosphorylation in human
      pancreatic cells.
AB  - Although nucleoside analogs as a group inhibit mtDNA replication, individually
      they target specific organs for toxicity. For example, dideoxyinosine (ddI) is
      most closely associated with clinical pancreatitis and dideoxycytosine (ddC) with
      peripheral neuropathy. Comparison of the differential effects of these analogs on
      mitochondrial function in relevant human cell lines could provide general clues
      as to the mechanisms of their differential toxicity. We compared the effects of
      ddI [and its intracellular metabolite dideoxyadenosine (ddA)], with other
      nucleoside analogs ddC, Azidothymidine (AZT) and didehydrodeoxythymidine (d4T) on
      mtDNA elongation, cytotoxicity, oxidative phosphorylation, and cellular ATP
      concentration in a human pancreatic cell line, Capan-1 cells. AZT, like all the
      other analogs tested, altered mtDNA elongation, but had no other effect on these
      cells. Both ddC and d4T, but not ddI (20 microm and 50 microM), reduced total
      dish protein (a measure of cell numbers) in cells grown to confluence. The effect
      of ddA was intermediate. All (except AZT) increased lactate concentration in the
      cell culture medium. Dideoxycytosine (ddC) and d4T did not significantly affect
      cell oxygen consumption, expressed as a fraction of total dish protein. By
      contrast, ddI and ddA reduced basal and/or FCCP-stimulated oxygen consumption.
      Dideoxycytosine (ddC) but not ddI or ddA (50 microM) was cytotoxic to cells after
      six days of growth. Nevertheless, the ATP content (expressed as a fraction of
      surviving cells) for ddC-, ddI-, and ddA-treated cells was similar to control
      cells. Cytotoxicity was apparent for ddI, ddA, as well as ddC after seven days.
      Paradoxically, cell ATP content was now significantly higher than control cells.
      Electron microscopy of cells treated with ddI confirmed significant
      ultrastructural changes affecting the inner mitochondria membrane and cristae. In
      conclusion, these data suggest that nucleoside analogs uniformly induce damage to
      mtDNA. However, the mitochondrial phenotypic damage induced by ddI and ddA appear
      to result in less Capan-1 cytotoxicity than ddC and d4T. The link between these
      differential effects and ddI pancreatitis is unclear.

PMID- 11575437
TI  - External biliary drainage plus bile acid feeding is not equal to internal
      drainage in preserving the cellular immunity following prolonged obstructive
      jaundice.
AB  - This study investigates the importance of intestinal bile flow in cellular
      immunity. Sprague-Dawley rats undergoing bile duct ligation (BDL) and sham
      ceiliotomy (Sham) for 14 and 21 days were investigated. Experimental animals
      following BDL were further divided into an external drainage (ED) group, an ED
      group with rat chow mixed with 2:2:1 cholic acid, chenodeoxycholic acid, and
      deoxycholic acid (ED + BF), and an internal drainage (ID) group. Fourteen days
      later, they were killed and analyzed for spleen lymphocytic [3H] thymidine uptake
      (LHU) under mitogen stimulation with phytohemagglutinin, blood biochemistry,
      hemogram, and liver pathology. In the 14-day BDL experiment, LHU and serum
      albumin level were decreased in the BDL group (P < 0.05). After drainage, they
      were not significantly different among sham, ED, ED + BF, and ID groups. In the
      21-day BDL experiment, the red cell volume was decreased (P < 0.05). After
      drainage, the ED, ED + BF, and ID groups still had a significantly lower LHU than
      the sham group (P < 0.05). However, the ID group had higher LHU than the ED and
      ED + BF groups (P < 0.05). The ED + BF group had a slightly higher LHU than the
      ED group but not statistically significant. Liver pathology returned to normal
      after drainage in the 14-day BDL model. In contrast, the 21-day BDL group had
      prominent periportal necrosis and developed periportal fibrosis after drainage.
      The present study reveals the duration of BDL determines the severity of hepatic
      damage. In the 14-day BDL groups, all kinds of drainage completely reverse the
      impaired liver function and cellular immunity. In the 21-day BDL group, 14-day
      drainage is inadequate for recovery because irreversible pathological changes are
      found. The reversal of cellular immunity in ID is better and faster, because it
      provides a better hepatic functional, nutritional, and hematological recovery
      besides the presence of primarily secreted bile acids.

PMID- 11575438
TI  - Lysophosphatidylcholine activates transcription factor NF-kappaB and AP-1 in
      AR42J cells.
AB  - Phospholipase A2 (PLA2) has been suggested in the pathogenesis of acute
      pancreatitis, in part through the PLA2-generated phospholipid by-products, most
      notably lysophosphatidylcholine (lyso-PC). The effects of lyso-PC on pancreatic
      acinar cells other than necrosis are poorly characterized. Recent studies have
      suggested a role of the activation of transcription factors such as nuclear
      factor kappa B (NF-kappaB) for the pathogenesis of acute pancreatitis. Here we
      examined the effects of lyso-PC on the activation of transcriptional factors in
      rat pancreatic AR42J cells. Lyso-PC induced apoptosis at concentrations > or = 10
      microM. At 10 and 25 microM, lyso-PC increased the NF-kappaB- and activator
      protein-1 (AP-1)-specific DNA binding activity as determined by electrophoretic
      mobility shift assay. Lyso-PC also increased the transcriptional activity of NF
      kappaB and AP-1 as assessed by luciferase assay. Lyso-PC increased the mRNA level
      of pancreatitis-associated protein-I and c-jun. Lyso-PC activated three classes
      of mitogen activated protein kinases: extracellular signal-regulated kinase 1/2,
      c-Jun NH2-terminal kinase/stress-activated protein kinase and p38 kinases.
      Activation of transcription factors by lyso-PC was not altered by a specific
      platelet activating factor receptor antagonist, TCV-309, suggesting that the
      activation was independent of the platelet activating factor receptor. These
      molecular events may suggest a novel role of lyso-PC for the modulation of acinar
      cell function.

PMID- 11575439
TI  - Acute pancreatitis due to captopril treatment.

PMID- 11575440
TI  - Human colon cancer cells deficient in DCC produce abnormal transcripts in
      progression of carcinogenesis.
AB  - Expressive loss of the tumor suppressor deleted in colon cancer (DCC) may be
      superior to lymph node status in predicting patient survival for intermediate
      stage colon cancer. A polymerase chain reaction (PCR)-based method for detecting
      DCC would be ideal as a prognostic indicator. DCC is an alternatively spliced
      molecule; thus, reliability of a PCR test for DCC will depend on amplifying only
      those regions of the molecule that are lost in the progression of colon cancer.
      For this reason, we studied a colon cancer cell line model at different stages of
      tumor progression to determine the alternative splice pattern for DCC. A
      commercially available colon cancer cell line system at different stages of tumor
      progression was used to identify which DCC exons are lost by western blot
      analysis, PCR, and RT-PCR techniques. Colon cancers express abnormal DCC
      transcripts. The proximal and distal exons are present (exons 2 and 28-29). Exons
      located in the center of the molecule are absent (6-7 and 18-23). This correlated
      to DCC protein loss in the cell lines. For clinical utility as a disease marker,
      exons in the middle portion of the DCC molecule that are spliced out should be
      utilized. Amplification of the proximal and distal regions will result in falsely
      concluding that DCC is present when its protein product is not expressed.

PMID- 11575441
TI  - Rigorous surveillance protocol increases detection of curable cancers associated
      with Barrett's esophagus.
AB  - Esophageal adenocarcinoma is increasing in incidence and has a high mortality
      unless detected early. Barrett's esophagus is the only known risk factor for this
      cancer; however, whether endoscopic surveillance reduces morbidity and mortality
      is controversial. Endoscopic cancer surveillance programes for Barrett's
      esophagus are not routinely practiced in the UK, and this is the first study to
      examine whether a rigorous surveillance protocol increases the detection rate of
      early oesophageal cancer. All patients with a diagnosis of Barrett's esophagus or
      associated adenocarcinoma attending Havering Hospitals NHS Trust between 1992 and
      1998 were included. A retrospective analysis was made of patients undergoing
      informal surveillance (96 patients, 1992-1997) and a prospective analysis was
      conducted following the implementation of a rigorous protocol (108 patients, 1997
      1998). Over the same time periods Barrett's associated cancers diagnosed in
      patients not undergoing surveillance were analyzed (262 patients 1992-1997, 98
      patients 1997-1998). From 1992 to 1997, one case of high-grade dysplasia was
      detected (N = 96, 1%). From 1997 to 1998, two cancers and three high-grade
      dysplasias were detected during rigorous surveillance (N = 108, 4.6%). Three of
      these patients have had curative esophagectomies (one high-grade dysplasia and
      two T1,N0,M0 tumors). In 1992-1997, 10 patients were found to have cancer in
      previously undiagnosed Barrett's esophagus (N = 262, 3.8%). Of 3/10 cancers
      treated surgically, one patient had a curative procedure (T1,N0,M0). In 1997
      1998, nine patients were found to have de novo Barrett's esophagus cancer (N =
      88, 10.2%) and three had curative resections (T1,N0,M0). Two of the patients with
      T1 lesions had no endoscopic evidence of cancer but were detected as a result of
      the multiple biopsy protocol. In conclusion, a rigorous biopsy protocol increases
      the detection of early cancer in Barrett's esophagus.

PMID- 11575442
TI  - Architecture and function of the gastroesophageal barrier in the piglet.
AB  - We describe the anatomy and function of the gastroesophageal barrier in the
      piglet. Male piglets underwent dissection (N = 6) and gastroesophageal muscle
      layer histometry (N = 6). Sedated, nonintubated animals (N = 13) underwent four
      probe perfusion esophageal manometry and the pressure profiles were related to
      the muscular thickness in the four quadrants. Hiatal and gastroesophageal anatomy
      are similar to our own. The muscle is thicker at the point where the clasp (on
      the right side) and sling fibers (on the left) concentrate. The pressure profiles
      were axially and radially asymmetric in coincidence with the thickness variations
      of the corresponding muscle layers. Sphincteric pressure was recorded as a
      plateau, whereas diaphragmatic crural pressure appeared as phasic oscillations in
      synchrony with respiration. The sphincter relaxed upon deglutition. In
      conclusion, the gastroesophageal structure and physiology are so similar in men
      and piglets that piglets are excellent models for research in this area.

PMID- 11575443
TI  - Effect of acute copper exposure on gastrointestinal permeability in healthy
      volunteers.
AB  - In vitro studies indicate that treating cells with copper results in alteration
      of tight junction permeability. In humans, ingestion of a single bolus of up to
      10 mg Cu/L (as copper sulfate) causes nausea and vomiting in approximately 20 and
      5% of the volunteers, respectively. To understand better the gastric and
      intestinal effects of copper, in this study we evaluated in asymptomatic
      volunteers (1) the effects of acute copper ingestion on gastric and intestinal
      permeability and (2) whether the appearance of gastrointestinal symptoms is
      associated with changes in mucosal permeability. Thirty-one asymptomatic subjects
      were assessed in a randomized, double-blind, crossover study that included two
      permeability tests, one after ingesting 200 ml distilled water and the other
      after ingesting 200 ml water containing 10 mg Cu/L (as copper sulfate). Fifteen
      minutes after ingestion subjects drank a second solution containing 40 g sucrose,
      7.5 g lactulose, and 2 g mannitol, and urine was collected for 5 hr. Sugar
      concentrations were determined by gas chromatography. Symptoms during the trials
      were recorded in self-administered questionnaires. Ingestion of the 10 mg/L
      copper solution significantly increased gastric permeability to sucrose [20.8
      (11.8-73.4) vs 28.4 (16.6-113.9) mg, respectively; P = 0.0064] but did not change
      intestinal permeability to lactulose/mannitol [0.87 (0.53-2.06) vs 1.17 (0.58
      2.39)%, respectively; P = 0.18]. Gastrointestinal symptoms were reported during
      both the basal and the experimental conditions, but after copper ingestion they
      increased to 22.6% of the subjects and were significantly more intense than under
      basal conditions (P = 0.047). However, changes in permeability were not related
      to the appearance of symptoms. These results indicate that acute oral exposure to
      10 mg Cu/L exerts an effect on gastric but not intestinal mucosa, reducing the
      gastric mucosal barrier capacity, independently of the appearance of
      gastrointestinal symptoms.

PMID- 11575444
TI  - Postprandial GLP-1, norepinephrine, and reactive hypoglycemia in dumping
      syndrome.
AB  - Rapid gastric emptying and exaggerated plasma concentrations of the
      insulinotropic hormone GLP-1 precede reactive hypoglycemia after oral glucose in
      gastrectomy patients. We suspected that the plasma volume drop associated with
      rapid gastric emptying (early dumping) would be accompanied by elevated plasma
      concentrations of norepinephrine. In order to study any relationship between
      postprandial norepinephrine, the enteroinsular axis, and plasma glucose, twelve
      patients with dumping syndrome and nine controls were studied. The plasma
      concentrations of norepinephrine, GLP-1, GIP, glucagon, insulin, and glucose were
      measured following a 1.5 g/kg lean body mass glucose meal. The early (0-30 min)
      integrated norepinephrine concentration was significantly higher in dumpers (22.1
      +/- 3.8 nmol/ml/min) compared to controls (14.7 +/- 3.1 nmol/ml/min; P < 0.001)
      and correlated closely with the postprandial hematocrit increment (r = 0.71; P <
      0.05). Early immunoreactivities of GLP-1, GIP, and glucagon peaked 30 min after
      glucose ingestion and were significantly higher in dumpers. Insulin peaked after
      60 min and correlated with early GLP-1. In 11 of the patients glucose fell below
      baseline after a median interval of 120 min. Glucose at 120 min, when most of the
      nadirs occurred was lowest in patients with high early GLP-1 concentrations (r =
      0.78; P < 0.001). Gel filtration chromatography of the dumpers' plasma revealed
      that pancreatic glucagon was detectable at time 0 and after 20 min, but not after
      120 min. It is concluded that in dumpers pancreatic glucagon is augmented in the
      early postprandial period, probably through stimulation by catecholamines. At 120
      min, when most of the hypoglycemias are encountered, pancreatic glucagon is no
      longer detectable, probably through inhibition by GLP-1.

PMID- 11575445
TI  - Prevention of acute NSAID-related gastroduodenal damage: a meta-analysis of
      controlled clinical trials.
AB  - No consensus exists as to whether cotherapy is effective in the short-term
      prevention of severe NSAID-related gastroduodenal damage. The aim of this study
      was to provide a quantitative systematic review of the efficacy of
      gastroprotective drugs, such as misoprostol, H2-blockers, and proton pump
      inhibitors (PPI) in preventing the severe acute NSAID-related gastroduodenal
      damage. Placebo-controlled randomized clinical trials on the use of misoprostol,
      H2-blockers, and PPIs as preventative agents published between January 1986 and
      May 1999 were identified through Medline and reference lists from clinical
      reviews. Studies on patients or healthy subjects were considered to be eligible
      for data pooling if they were performed in acute NSAID users (not longer than 30
      days) and with at least one endoscopic evaluation during therapy that reported
      results specifically for gastric and duodenal damage. Risk difference (RD),
      heterogeneity chi2 test, publication bias assessment and number needed to treat
      (NnT) were calculated for each meta-analysis by a customized program. Twenty-one
      trials met the inclusion criteria evaluating a total of 636 healthy subjects and
      1904 patients with arthritis randomized to active drug or placebo. The baseline
      risk of NSAID-related gastric (68% vs 16.6%, P < 0.001) and duodenal (22% vs
      8.5%, P < 0.001) damage was higher in healthy subjects compared to patients with
      arthritis. Meta-analysis demonstrated a significant heterogeneity between trials
      performed in the two populations (P < 0.0001). In healthy subjects the active
      drug treatment induced a significant prevention of severe gastric (misoprostol RD
      = 69%, 95% CI = 60.3-77.7, H2-blocker RD = 38.3%, 95% CI = 17.8-58.9 and PPI RD =
      43%, 95% CI = 28.2-57.7) and duodenal damage (misoprostol RD = 22.3%, 95% CI =
      13.6-31, H2-blocker RD = 13.2%, 95% CI = 5.2-21.3 and PPI RD = 17.7%, 95% CI =
      3.5-31.8). NnT values were, respectively, 1, 3, and 2 for gastric and 4, 8, and 6
      for duodenal damage. In patients with arthritis lower RD and higher NnT values
      were found compared to healthy subjects. In conclusions, cotreatment with
      gastroprotective drugs for short-term prevention of severe gastroduodenal NSAID
      related damage was more effective in healthy subjects than in patients with
      arthritis; misoprostol and PPIs were more effective than H2-blockers in the
      prevention of both gastric and duodenal severe damage; more studies need to
      evaluate the role of short-term prevention in patients with arthritis who require
      acute NSAID treatment.

PMID- 11575446
TI  - Compliance measurement of lower esophageal sphincter and esophageal body in
      achalasia and gastroesophageal reflux disease.
AB  - Little is known about the effect of achalasia and gastroesophageal reflux disease
      (GERD) on compliance of the esophageal body and the lower esophageal sphincter
      (LES). Twenty-two patients with achalasia, 14 with GERD, and 14 asymptomatic
      volunteers were assessed. Recording apparatus consisted of a specially developed
      PVC bag tied to a compliance catheter, a barostat, and a polygraph. Intrabag
      pressures were increased incrementally while the bag volume was recorded. In each
      subject, pressure-volume graphs were constructed for both the esophageal body and
      LES and the compliance calculated. In achalasia, compliance of the esophageal
      body was significantly higher (P < 0.01) than in controls, whereas LES compliance
      was similar. Patients with GERD had a highly compliant LES in comparison to both
      controls and to patients with achalasia (P < 0.01 and P < 0.001, respectively);
      however there was no difference in their esophageal body compliance. In
      conclusion, foregut motility disorders can cause changes in organ compliance that
      are detectable using a barostat and a suitably designed compliance bag. Further
      measurement of compliance may provide clues to the pathogenesis of these
      disorders.

PMID- 11575447
TI  - Characterization of virulence factors of mouse-adapted Helicobacter pylori strain
      SS1 and effects on gastric hydrophobicity.
AB  - Gastric infection with Helicobacter pylori results in chronic active gastritis
      and in some individuals is associated with complications such as peptic
      ulceration and gastric cancers. A balance between bacterial factors and host
      responses may determine disease outcome. The mouse-adapted H. pylori strain SS1
      has been utilized as a model to study disease pathogenesis. Although chronic
      gastritis is observed in this murine model of H. pylori infection, other
      complications of disease seen in the human host (such as peptic ulceration) are
      not identified. The objectives of this study were to characterize virulence
      factors of the mouse-adapted H. pylori strain SS1 and determine host responses to
      infection. Vacuolating cytotoxin activity of H. pylori strain SS1 was determined
      after incubation of HEp-2 cells with culture supernatant for 24 hr. Polymerase
      chain reaction was performed to detect the presence of the cagA and cagE genes.
      Chemokine responses from human gastric epithelial cells infected with H. pylori
      SS1 were assessed by measurement of the concentration of interleukin-8 in cell
      free supernatants. C57BL/6 and gld mice were infected with strain SS1 or sham
      infected. Eight weeks following infection, gastric tissues were obtained for
      histological analysis and surface hydrophobicity was measured by axisymmetric
      drop-shape analysis. H. pylori strain SS1 was cytotoxin negative, cagA positive,
      and cagE positive, but induced only a modest interleukin-8 response (684 +/- 140
      pg/ml) from AGS gastric epithelial cells in comparison to a clinical isolate
      (4170 +/- 410 pg/ml, P < 0.0005). Increased inflammation was observed in the
      stomachs of H. pylori strain SS1-infected animals compared to uninfected
      controls. Gastritis was not associated with any disease complications. Despite
      mucosal inflammation, infected mice did not demonstrate alterations in gastric
      surface hydrophobicity (42.2 degrees +/- 2.2 degrees and 41.4 degrees +/- 3.2
      degrees for C57BL/6 and gld, respectively) compared to uninfected mice (43.2
      degrees +/- 2.3 degrees and 39.5 degrees +/- 1.6 degrees, respectively). In
      conclusion, murine infection with H. pylori SS1, which contains putative
      bacterial virulence factors, results in gastric inflammation. However, the
      mucosal changes are not associated with alterations in surface hydrophobicity.
      Therefore, the mouse model of infection with H. pylori, strain SS1 may not serve
      as an entirely appropriate model to study host factors associated with disease
      complications.

PMID- 11575448
TI  - Impairment of gastric secretion modulation in duodenal ulcer and in long-term PPI
      treatment: quantitative morphologic findings and pathophysiologic implications.
AB  - Helicobacter pylori affects gastric secretion. This functional effect might have
      a morphometric counterpart. Therefore, the gastric cell secretory compartment was
      morphometrically assessed in different pathophysiologic conditions related to
      Helicobacter pylori infection. Nineteen Helicobacter pylori-positive nonduodenal
      ulcer subjects, 15 omeprazole chronically treated subjects, and 19 duodenal ulcer
      patients were studied against 19 controls. Somatostatin, gastrin,
      enterochromaffin-like, and parietal cell density was assessed in gastric
      biopsies. No differences in any cell type density were found between Helicobacter
      pylori-positive nonduodenal ulcer subjects and controls. On the contrary,
      differences were significant when comparing omeprazole and duodenal ulcer
      patients to controls (higher density of gastrin, enterochromaffin-like, and
      parietal cells, lower density of somatostatin cells). In duodenal ulcer a
      reversion to control values followed Helicobacter pylori eradication and ulcer
      healing. A direct linear correlation between enterochromaffin-like, gastrin, and
      parietal cell density was demonstrated. An almost complete map of mucosal cells
      involved in gastric secretion is provided by this study. The cell density
      pattern, identical to the omeprazole group, points to an impaired feedback
      control of secretion in duodenal ulcer. The reversion to control values after
      Helicobacter pylori eradication and ulcer healing demonstrates the pathogenetic
      role of Helicobacter pylori-host interaction in these changes.

PMID- 11575449
TI  - Achalasia with high-amplitude esophageal body contractions: a case presentation
      of truly vigorous achalasia.

PMID- 11575450
TI  - Rectal passage of intestinal endometriosis.

PMID- 11575452
TI  - Enterotachogram analysis to distinguish irritable bowel syndrome from Crohn's
      disease.
AB  - Crohn's disease is often initially misdiagnosed as irritable bowel syndrome. The
      goal of this research was to determine if computerized auscultation (fasting
      enterotachogram analysis) could have a role in distinguishing between these
      diagnoses. Patients with irritable bowel syndrome, Crohn's disease, and a control
      group were enrolled in the study. The fasting sound-to-sound interval, standard
      deviation of the interval, sounds per minute, and percentage time involved with
      bowel sounds was determined by computerized enterotachogram analysis. The mean
      sound-to-sound interval for the Crohn's group (1232 msecs) and the controls (1706
      msecs) was significantly higher than the irritable bowel group (511 msecs, P <
      0.0001). We conclude that Crohn's is not characterized by a shortened interval.
      The high negative predictive value of the fasting enterotachogram for irritable
      bowel syndrome suggests that an interval greater than 740 msecs should trigger a
      search for an alternative diagnosis to irritable bowel. Crohn's disease should be
      included in that differential.

PMID- 11575451
TI  - Butyrate inhibits interleukin-1-mediated nuclear factor-kappa B activation in
      human epithelial cells.
AB  - Nuclear factor-kappa B (NF-kappaB) is a critical transcription factor for the
      inducible expression of multiple genes involved in inflammation. NF-kappaB is
      sequestered in the cytoplasm by inhibitory IkappaB proteins. Extracellular
      stimuli, notably interleukin-1beta (IL-1beta) and tumor necrosis factor alpha
      (TNF-alpha) activate NF-kappaB nuclear translocation via IkappaB phosphorylation
      and degradation. Since previous reports suggest that the short chain fatty acid
      butyrate has antiinflammatory properties, the effects of butyrate on NF-kappaB
      nuclear translocation in human epithelial cells (HeLa229) were tested. In cells
      pretreated with butyrate, a time- and dose-dependent inhibition of IL-1beta
      mediated NF-kappaB nuclear translocation was observed. However, IkappaB alpha
      phosphorylation and degradation occurred rapidly in both butyrate pretreated and
      nonpretreated cells, respectively. These data indicate that inhibition of IL
      1beta-induced NF-kappaB activation by butyrate does not require an intact IkappaB
      alpha protein.

PMID- 11575453
TI  - Intestinal regrowth is amplified after jejunal but not ileal resection during
      tapeworm infection in the rat.
AB  - The ileum possesses functions required by a healthy individual that are not fully
      supplanted by the duodenum or jejunum. Evidence suggests that the ileum may also
      be necessary to maintain an enteric parasite-host interaction. We hypothesized
      that the ileum is essential to the survival of the lumen-dwelling, rat tapeworm,
      H. diminuta. Male rats were divided into three groups: those with ileal or
      jejunal resections and nonresected controls. Half of each rat group was infected
      with the tapeworm. After jejunal resection, the weight but not length of
      intestinal remnant (duodenum + ileum) in infected rats returned to that of
      control, nonresected intestine 29 days after surgery and tapeworm numbers were
      fully maintained. In contrast, after ileal removal intestinal length and weight
      of the remaining duodenum and jejunum in infected rats were significantly
      decreased and tapeworm survival diminished. Data indicates that intestinal growth
      following resection is amplified by tapeworm infection when the ileum remains but
      diminished when the ileum is removed. Furthermore, loss of the ileum results in
      decreased infection intensity and dry weight of the tapeworm.

PMID- 11575454
TI  - Somatostatin antagonism prevents elemental diet-induced intestinal atrophy in the
      rat.
AB  - Somatostatin is a peptide with known antiproliferative effects on the intestine.
      The aim of the present work was to determine whether somatostatin (SST)
      antagonism reduces elemental diet-induced intestinal atrophy in the rat. Male
      Wistar rats were fed a standard diet and treated for seven days with either
      continuous infusion of saline or low and high doses of a putative somatostatin
      antagonist; another group was given a SST antagonist in a pulsatile high dose.
      All these groups received an elemental diet to induce gut mucosa atrophy. Rats
      were killed and samples were obtained for morphometric and proliferative
      measurements of the intestine and for SST and insulin-like growth factor-1 (IGF
      1) level determination. The elemental diet decreased mucosal length and
      proliferation. Pulsatile administration of SST antagonist improved or prevented
      both effects, whereas continuous SST antagonist delivery prevented decreased
      crypt proliferation induced by the elemental diet. Somatostatin plasma levels
      were lowest in rats receiving pulsatile administration of SST antagonist. In
      conclusion, somatostatin antagonism increases proliferation in the intestinal
      mucosa, improving elemental diet-induced intestinal atrophy; however,
      morphological growth is not affected.

PMID- 11575455
TI  - Loading of mechanical pressure activates mitogen-activated protein kinase and
      early immediate gene in intestinal epithelial cells.
AB  - Intestinal mucosa is continuously exposed to mechanical forces. We examined
      whether pressure loading activates mitogen-activated protein kinase (MAPK) and
      expression of early immediate genes in intestinal epithelial cells. Pressure was
      applied to IEC18 cells by helium gas in a culture flask and pressure-induced cell
      proliferation was examined. The expression of early immediate genes, MAPK
      activity, and activation of nuclear factor activator protein-1 (AP-1) were also
      examined. Pressures significantly promoted cell proliferation with peak effect at
      80 mm Hg. Pretreatment with either a protein kinase C inhibitor or tyrosine
      kinase inhibitors, but not calcium chelating agents significantly inhibited cell
      proliferation promoted by pressure. Early inductions of c-myc and c-fos proteins,
      increased activity of MAPK, and activation of AP-1 were observed by pressure
      loading. Our study showed that intestinal mucosal cell proliferation is promoted
      by mechanical pressure and various intracellular signaling pathways are involved
      in the process.

PMID- 11575456
TI  - IL-5 and TNF-alpha participate in recruitment of eosinophils to intestinal mucosa
      in ulcerative colitis.
AB  - There is an increased influx of activated eosinophils to the intestinal mucosa in
      active ulcerative colitis, and an increased release of eosinophil-derived
      proteins, such as ECP, has also been observed. These findings indicate that
      eosinophils may contribute to tissue damage and intestinal inflammation in this
      disease. The relative importance of different chemotactic factors and the impact
      of steroid treatment on their effect in active ulcerative colitis are not known.
      We measured the eosinophil chemotactic activity in perfusion fluids from 11
      patients with ulcerative colitis before and after steroid treatment and from 7
      control patients. The effect of neutralizing antibodies to IL-5 and -8, RANTES,
      eotaxin, MCP-3, TNF-alpha, GM-CSF was investigated. The chemotactic activity was
      higher in perfusion fluids from patients than from controls (P = 0.0043). Anti-IL
      5 (P = 0.005) and -TNF-alpha (P = 0.017) inhibited the activity in perfusion
      fluids obtained before treatment. Steroid treatment prevented the effect of all
      antibodies but had no significant effect on the chemotactic activity. The
      chemotactic activity correlated with the levels of eosinophil granule proteins in
      the perfusion fluids. In conclusion, in ulcerative colitis, eosinophils are
      attracted to the intestinal tissue by chemotactic factors, of which IL-5 and TNF
      alpha may be the most prominent steroid-sensitive ones. The steroid-insensitive
      chemotactic activities remain unidentified.

PMID- 11575457
TI  - Combination therapy with Bifidobacterium breve, Lactobacillus casei, and
      galactooligosaccharides dramatically improved the intestinal function in a girl
      with short bowel syndrome: a novel synbiotics therapy for intestinal failure.

PMID- 11575458
TI  - Ursodeoxycholic acid and in vitro vasoactivity of hydrophobic bile acids.
AB  - Lipophilic bile acids, such as deoxycholic acid (DCA), are nonspecific
      endothelium-independent vasorelaxants whose underlying basis is complex,
      involving membrane calcium channels blockade and receptor antagonism. The
      vasorelaxant action of these acids has also been linked to the generation of
      reactive oxygen species and an increased extent of lipid peroxidation.
      Ursodeoxycholic acid (UDCA) is a naturally occurring tertiary dihydroxy
      hydrophilic acid whose mechanism of action has been attributed to minimizing the
      effects of lipophilic bile acids. Hence, we considered UDCA might be a useful
      pharmacological tool to delineate the role of enhanced lipid peroxidation in
      lipophilic bile acid-induced vasorelaxation. UDCA abrogates in vitro DCA-induced
      vasorelaxation in rat aortic rings and can suppress DCA-initiated lipid
      peroxidation in vascular smooth muscle microsomal membrane fractions prepared
      from the rat aortae. Three different studies were performed. In study 1, the
      ability of UDCA to restore the DCA-blunted contractile response to the alpha1
      adrenoceptor, phenylephrine in rat aortic rings, was evaluated. In study 2, the
      ability of UDCA to restore DCA-induced vasorelaxation in precontracted rat aortic
      rings was assessed. In study 3, the ability of UDCA to suppress the increased
      extent of lipid peroxidation effected by DCA in vascular smooth muscle microsomal
      membrane fractions prepared from rat aortae was measured using the thiobarbituric
      acid reactive substance (TBARS) assay. UDCA, at a concentration equivalent to
      that seen in the plasma of patients with cholestatic liver disease treated with
      the bile acid, partially restored DCA-induced impaired contractility, prevented
      DCA-induced vasorelaxation, and abolished DCA-induced increases in the extent of
      lipid peroxidation. In conclusion, these data suggest that DCA-induced
      vasorelaxation is mediated by increasing the extent of lipid peroxidation in
      vascular tissue.

PMID- 11575459
TI  - Serum collagen type VI and XIV and hyaluronic acid as early indicators for
      altered connective tissue turnover in alcoholic liver disease.
AB  - Hepatic fibrosis in alcoholic liver disease often heralds progression to
      cirrhosis and, therefore, noninvasive parameters are required for early diagnosis
      and follow-up. Collagens VI and XIV, procollagen-III-N-propeptide, hyaluronic
      acid, and active transforming growth factor-beta1 (TGF-beta1) were measured in
      healthy volunteers, patients with alcoholic cirrhosis, and heavy drinkers without
      cirrhosis. Noncirrhotic alcoholics were assigned to two groups with either normal
      aspartate aminotransferase or levels > or = 2 normal. Collagens VI and XIV were
      elevated in all alcoholic patients compared to controls (P < 0.0001, all
      instances). Procollagen-III-N-propeptide and hyaluronic acid levels were higher
      in alcoholic patients with elevated liver enzymes and in cirrhotics as compared
      to controls. Procollagen-III-N-propeptide revealed a significant correlation with
      serum levels of TGF-beta1 (P < 0.0001). Collagens VI, and XIV, procollagen-III-N
      propeptide, and hyaluronic acid appear to be sensitive markers indicating
      fibrotic transformation in alcoholics. The correlation between procollagen-III-N
      propeptide and TGF-beta1 emphasizes its role in hepatic fibrogenesis.

PMID- 11575460
TI  - Coagulation protein function: enhancement of the anticoagulant effect of
      acetaldehyde by sulfated glycosaminoglycans.
AB  - In view of the increased anticoagulant effect of acetaldehyde-treated heparin,
      other glycosaminoglycans (GAGs) such as chondroitin sulfates A and C, dermatan
      sulfate (chondroitin sulfate B), heparan sulfate, and hyaluronic acid were tested
      for anticoagulant activity before and after exposure to acetaldehyde. Clotting
      times of human plasma Ci-Trol coagulation control, level I (Baxter Healthcare
      Corp.), were tested in the presence of 1.8, 3.0, 3.6, or 4.5 microg heparin
      (0.32, 0.54, 0.64, 0.81 units heparin). Additionally, 9, 27, or 90 microg of
      chondroitin sulfates A, B, or C was utilized in lieu of heparin. The effects of 2
      microg heparin (0.36 units), chondroitin sulfates A, B, and C, (20 microg each),
      2 microg heparan sulfate, and 2 microg hyaluronic acid, respectively, in the
      presence of 44.7 mM acetaldehyde on the clotting time of plasma were studied. It
      was observed that chondroitin sulfate B (dermatan sulfate) prolonged the clotting
      time of plasma, although to a lesser extent than heparin. Chondroitin sulfates A
      and C, heparan sulfate, and hyaluronic acid did not prolong clotting time.
      However, pretreatment of all the sulfated GAGs with acetaldehyde gave products
      that enhanced the anticoagulant effect of acetaldehyde, notwithstanding the lack
      of anticoagulant effect of the GAGs. In contrast, hyaluronic acid exhibited no
      effect upon clotting time nor did its acetaldehyde-treated product. Furthermore,
      ethanol exhibited no effect upon the clotting times of the GAG-plasma mixtures.
      These results suggest that sulfated GAGs may be modified by acetaldehyde, a
      component of plasma in chronic alcoholics, and that the resultant products may
      contribute to the prolonged clotting times.

PMID- 11575461
TI  - A case of coexisting primary biliary cirrhosis and primary sclerosing
      cholangitis: a new overlap of autoimmune liver diseases.
AB  - Although the etiology of AIH, PBC, and PSC remains unknown, it is apparent that
      these autoimmune liver diseases share many common features and can coexist in the
      same patient. Our patient had features of PBC and later clearly developed a
      picture of PSC. This case suggests that PBC, PSC, AIH, and autoimmune cholangitis
      are part of a spectrum of chronic autoimmune liver disease that develop in
      response to some yet unidentified antigen.

PMID- 11575462
TI  - Simulation studies of the ischemic vulnerability of the subendocardium.
AB  - Changes in the subendo-subepi flow ratio were studied by using a simple
      electronic circuit model of the coronary vessel consisting of a resistor,
      capacitor and field effect transistor in order to provide a better understanding
      of the ischemic vulnerability of the subendocardium. The simulated subendo-subepi
      flow ratio was found to be approximately 1.2 under normal condition. Changes in
      the flow ratio were observed while varying the main arterial resistance, mean
      arterial pressure and intramyocardial pressure individually. The mean flow in the
      subendocardium was found to decrease at a rate faster than that in the
      subepicardium with the increase in the septal arterial resistance and the
      intramyocardial pressure. The same tendency was also observed while the arterial
      pressure was lowered. This decrease in the mean subendocardial flow is considered
      to be the effect of higher end-systolic resistance in the subendocardial venule
      compared to that in the subepicardial venule. These results would be helpful in
      understanding the vulnerability of the subendocardium to ischemia and in
      providing clinical treatment to patients with that disease.

PMID- 11575463
TI  - Mechanism of burn injury during magnetic resonance imaging (MRI)--simple loops
      can induce heat injury.
AB  - To determine the mechanism of burn injury associated with magnetic resonance
      imaging (MRI), the induced current in the loops of a conductive lead was
      measured. Seven types of loops with effective areas within the range from 100 to
      12 000 cm2 were made and then each loop was placed in the bore of a whole-body MR
      system at 0.5 T and MRI was carried out. During radio frequency (RF) irradiation,
      an induced voltage was observed in loops that were placed with their axes
      parallel to the linearly polarized transmitting RF field. The voltage had a
      sincfunction characteristic and was within the range 55-235 V at the RF pulse
      sequence for usual MR imaging. When the axis was vertical, negligible current was
      observed. A resistor inserted into the circuit of a 30 x 40 cm loop sparked and
      burned out. Simple loops of conductive material may result in the induction of a
      large and potentially hazardous voltage in the imaging system. Self-resonance of
      such a loop may add greatly to hazards by increasing the effective coupling to
      the RF transmitter. Also, impedance matching of the inserted resistor with the
      impedance of the loop increases the dissipated power at the resistor.

PMID- 11575465
TI  - Domestic pharmaceutical production in 1999 reaches yen 6.29 trillion.

PMID- 11575464
TI  - ECG data reduction method for medical telemetry systems.
AB  - In current medical practice, all transmitters used for monitoring an ECG send
      data continuously. If transmission could be limited to only the ECG data that
      requires the attention of a technician, the likelihood of interference and power
      consumption would be reduced considerably. In this paper, we propose a new ECG
      telemetry system. The transmitter has a simple ECG analyzer and it only transmits
      data when abnormal waveforms are detected. As part of this system, we propose a
      simple algorithm to detect an abnormal ECG. The algorithm is composed of a
      baseline drift canceller (utilizing a moving average calculation), a waveform
      detector (using a modified second order derivative) and an ECG analyzer. In order
      to test the effectiveness and feasibility of the algorithm, computer simulations
      (with a MIT-BIH ECG database) and experiments (with microprocessor-based
      hardware) were performed. The results of the simulations show that the detection
      performance and data compression performance of the algorithm are adequate. The
      results of the experiment show that the algorithm even performs adequately when
      used with microprocessor-based hardware that is of limited size or limited power
      consumption.

PMID- 11575466
TI  - Biomedical Imaging and Bioengineering Institute authorized at the National
      Institutes of Health (NIH).

PMID- 11575467
TI  - Not innocent, though 'not guilty'.

PMID- 11575468
TI  - Impedance computed tomography using an adaptive smoothing coefficient algorithm.
AB  - In impedance computed tomography, a fixed coefficient regularization algorithm
      has been frequently used to improve the ill-conditioning problem of the Newton
      Raphson algorithm. However, a lot of experimental data and a long period of
      computation time are needed to determine a good smoothing coefficient because a
      good smoothing coefficient has to be manually chosen from a number of
      coefficients and is a constant for each iteration calculation. Thus, sometimes
      the fixed coefficient regularization algorithm distorts the information or fails
      to obtain any effect. In this paper, a new adaptive smoothing coefficient
      algorithm is proposed. This algorithm automatically calculates the smoothing
      coefficient from the eigenvalue of the ill-conditioned matrix. Therefore, the
      effective images can be obtained within a short computation time. Also the
      smoothing coefficient is automatically adjusted by the information related to the
      real resistivity distribution and the data collection method. In our impedance
      system, we have reconstructed the resistivity distributions of two phantoms using
      this algorithm. As a result, this algorithm only needs one-fifth the computation
      time compared to the fixed coefficient regularization algorithm. When compared to
      the fixed coefficient regularization algorithm, it shows that the image is
      obtained more rapidly and applicable in real-time monitoring of the blood vessel.

PMID- 11575469
TI  - Study of a (trimethylenecarbonate-co-epsilon-caprolactone) polymer--part 2: in
      vitro cytocompatibility analysis and in vivo ED1 cell response of a new nerve
      guide.
AB  - Future surgical strategies to restore neurological function in peripheral nerve
      loss may involve replacement of nerve tissue with cultured Schwann cells using
      biodegradable guiding implants. Random copolymers of trimethylene carbonate and
      epsilon caprolactone (P(epsilonCL-TMC), 50: 50) have been synthesized by ring
      opening polymerization using rare earth alkoxides as initiator. Their potential
      use as nerve guide repairs has been assessed through indirect and direct in vitro
      biocompatibility tests and in vivo soft tissue response to EDI subclass
      macrophages. In vitro, we exposed monolayers of human skin fibroblasts and an
      established continuous cell line (Hela) to liquid extracts (either pure or
      diluted in the culture medium) of epsilonCL-TMC copolymer including positive
      (phenol) and negative controls. Then, colorimetric assays (Neutral red and MTT)
      were performed. The extracts of epsilonCL-TMC induced no significant cytotoxic
      effect. We also exposed in vitro Schwann cells to pieces of P(epsilonCL-TMC) and
      P(LA-GA) copolymers. We evaluated cell attachment at 1 and 3 h by measuring the
      activity of the lysosomal enzyme (N-acetyl-beta-hexosaminidase) and cell
      proliferation at 1, 3, 6 and 9 days by measuring the cell metabolic activity (MTT
      assay). Values for attachment slightly decreased between 1 and 3 h but were
      significantly higher than on agars (negative control). Cells plated on epsilonCL
      TMC showed a rate of proliferation comparable with that of normalized controls
      and higher than on PGA-PLA at day 9. Finally, we evaluated in vivo the soft
      tissue response after implantation of cylindrical tubes of P(epsilonCL-TMC) and
      P(LA-GA) copolymers with an immunohistochemistry staining procedure for the newly
      recruited ED1 macrophages. An image analysis system automatically measured the
      optical density of labelled positive ED1 cells at 9, 21 and 60 days after
      implantation. epsilonCL-TMC copolymer showed a mild soft tissue reaction with no
      adverse chronic inflammatory reaction. These data allowed us to consider this
      conduit as a potential effective substitute in nerve repair. El sevier Science
      Ltd. All rights reserved.

PMID- 11575470
TI  - The effect of chitin and chitosan on the proliferation of human skin fibroblasts
      and keratinocytes in vitro.
AB  - The effects of chitin [(1 --> 4)-2-acetamido-2-deoxy-beta-D-glucan] and its
      partially deacetylated derivatives, chitosans, on the proliferation of human
      dermal fibroblasts and keratinocytes were examined in vitro. Chitosans with
      relatively high degrees of deacetylation strongly stimulated fibroblast
      proliferation while samples with lower levels of deacetylation showed less
      activity. Fraction, CL313A, a shorter chain length, 89% deacetylated chitosan
      chloride was further evaluated using cultures of fibroblasts derived from a range
      of human donors. Some fibroblast cultures produced a positive mitogenic response
      to CL313A treatment with proliferation rates being increased by approximately 50%
      over the control level at an initial concentration of 50 microg/ml, whilst others
      showed no stimulation of proliferation or even a slight inhibition (< 10%). The
      stimulatory effect on fibroblast proliferation required the presence of serum in
      the culture medium suggesting that the chitosan may be interacting with growth
      factors present in the serum and potentiating their effect. In contrast to the
      stimulatory effects on fibroblasts, fraction CL313A inhibited human keratinocyte
      mitogenesis with up to 40% inhibition of proliferation being observed at 50
      microg/ml. In general highly deacetylated chitosans were more active than those
      with a lower degree of deacetylation. These data demonstrate that highly
      deacetylated chitosans can modulate human skin cell mitogenesis in vitro.
      Analysis of their effects on cells in culture may be useful as a screen for their
      potential activity in vivo as wound healing agents, although in the case of
      fibroblasts it is important to select appropriate strains of cells for use in the
      screen.

PMID- 11575471
TI  - Relationship between complement activation, cellular uptake and surface
      physicochemical aspects of novel PEG-modified nanocapsules.
AB  - The aim of our work was to examine the relationship between modifications of the
      surface of nanocapsules (NC) by adsorption or covalent grafting of poly(ethylene
      oxide) (PEG), and changes in their phospholipid (PL) content on complement
      activation (C3 cleavage) and on uptake by macrophages. The physicochemical
      characterization of the NC included an investigation of their properties, such as
      surface charge, size, hydrophilicity, morphology and homogeneity. This is the
      first time that such properties have been correlated with biological interactions
      for NC, a novel carrier system with a structure more complex than nanospheres. C3
      crossed immunoelectrophoresis revealed the reduced activation for NC with longer
      PEG chain and higher density, although all formulations induced C3 cleavage to a
      lesser or greater extent. NC bearing PEG covalently bound to the surface were
      weaker activators of complement than plain PLA [poly(D,L-lactide)] NC or
      nanospheres (NS). Furthermore, the fluorescent/confocal microscopy of J774A1
      cells in contact with NC reveal a dramatically reduced interaction with PEG
      bearing NC. However, the way in which PEG was attached (covalent or adsorbed)
      seemed to affect the mechanism of uptake. Taken together, these results suggest
      that the low level of protein binding to NC covered with a high density of 20kDa
      PEG chains is likely to be due to the steric barriers surrounding these
      particles, which prevents protein adsorption and reduces their interaction with
      macrophages.

PMID- 11575472
TI  - Petal-like apatite formed on the surface of tricalcium phosphate ceramic after
      soaking in distilled water.
AB  - In the present study six types of tricalcium phosphate ceramic were prepared and
      soaked in distilled water for different periods to investigate whether a surface
      apatite layer was formed on TCP ceramics or not. X-ray diffractometry (XRD) and
      Fourier-transformed infrared (FTIR) spectrometer were used to examine the changes
      in crystalline phases and functional groups of TCP ceramics for different soaking
      periods. Calcium and phosphate ions released from TCP ceramics during soaking
      were recorded by atomic absorption analysis and ion-coupled plasma. Results
      revealed that alphaTCP, alphaTCP/betaTCP mixture (alphabetaTCP) and betaTCP
      ceramic were gradually dissolved. There was no apatite layer formed on their
      surface after being immersed in distilled water for different durations of time.
      Mg-TCP ceramic, tricalcium phosphate doped with Mg ions, exhibited a lower
      dissolution rate than the other types of TCP ceramics. Apatite crystals were also
      not formed on the surface of Mg-TCP ceramic when immersed in distilled water.
      Tribasic calcium phosphate, prepared from wet precipitation method, was converted
      to betaTCP/HAP (HbetaTCP) or alphaTCP/betaTCP/HAP (HalphabetaTCP) crystalline
      composition at different sintering temperatures (1,150 degrees C and 1,300
      degrees C). The surface apatite layer did not appear on HbetaTCP ceramic after
      soaking. We observed that petal-like apatite was formed on the HalphabetaTCP
      ceramic surface after being immersed for 2 weeks. alphaTCP phase of HalphabetaTCP
      ceramic was not directly converted to apatite during soaking. The surface apatite
      layer formed on the HalphabetaTCP ceramic surface was due to the precipitation of
      the calcium and phosphate ions released from alphaTCP dissolution. HAP, which
      existed in the structure of HalphabetaTCP ceramic, plays a role as apatite
      precipitating seed to uptake calcium and phosphate ions. TCP ceramics which
      lacked alphaTCP and HAP content neither converted to apatite nor formed surface
      apatite on their surfaces during immersion.

PMID- 11575473
TI  - Accumulation of cyclic AMP in Swiss 3T3 cells adhering to a cellulose biomaterial
      substratum through interaction with adenylyl cyclase.
AB  - Controlling cell shape induced by cell-substrata interaction appears of prime
      importance to influence subsequent biological processes such as cell migration,
      proliferation, differentiation or apoptosis. Studies on Swiss 3T3 fibroblasts
      have recently provided evidence that cell spreading is mediated by integrins and
      RhoA. Our previous studies showed that on Cuprophan, a cellulose membrane (CU) to
      which vitronectin adhesive protein is poorly adsorbed, Swiss 3T3 cells are
      rounded and undergo cAMP-dependent aggregation. In contrast, on a
      polyacrylonitrile membrane (AN69) that favours the adsorption of vitronectin and
      fibronectin, cells spread out and contain low concentrations of cAM P. We have
      now examined the parts played by the three components in the cAMP pathway
      (receptors, G-proteins and adenylyl cyclase itself) in cAM P-dependent cell
      aggregation on CU. Experiments with intact cells showed no interaction between
      the CU and receptors, or between the CU and G-proteins. Assays on membrane
      preparations plus the Mn-ATP substrate, which uncouples G-proteins and adenylyl
      cyclase, demonstrated that activation of the cAMP pathway by CU depends primarily
      on the catalytic activity of the adenylyl cyclase. These investigations provide
      essential data for the development of biomaterials that favour cell
      functionality.

PMID- 11575474
TI  - Design and evaluation of drug-loaded wound dressing having thermoresponsive,
      adhesive, absorptive and easy peeling properties.
AB  - In order to develop a novel unique wound dressing, a combination of self-adhesive
      Eudragit E film with antibacterial drug-loaded poly (N-isopropyl-acrylamide)
      (PNIPAAm) microgel beads was designed. The result indicates that the tack
      property of Eudragit E film increased with an increase of the PNIPAAm microgel
      beads added, but there was no significant difference between the dried PNIPAAm
      microgel beads with or without adsorbing drug. In addition, the peel strength of
      Eudragit E film initially decreased with the addition of PNIPAAm microgel beads,
      but increased to a maximum value when PNIPAAm microgel beads were added from 4%
      to 7.6%. then decreased again after 7.6%. The optimal concentration of PNIPAAm
      microgel beads was 7.6% (w/v) which had better tack and peel adhesive properties.
      The water uptake ratio of Eudragit E film containing PNIPAAm microgel beads was
      found to be temperature-dependent, suggesting that the Eudragit E film containing
      PNIPAAm microgel beads enabled to absorb the wound fluid. Eudragit E film
      containing PNIPAAm microgel beads with or without adsorbing drug had
      significantly reduced peel strength after 12 h-immersion in solution. All these
      results suggest that a novel drug-loaded wound dressing has been developed by
      binding a self-adhesive Eudragit E film with an antibacterial drug-loaded PNIPAAm
      microgel beads to achieve thermo-responsive, adhesive, absorptive and easy
      peeling functions.

PMID- 11575475
TI  - Rheological properties of PMMA bone cements during curing.
AB  - The rheological behaviour of poly(methyl methacrylate) bone cements has been
      characterised during the curing phase using an oscillating parallel plate
      rheometer. Viscosity has been measured as a function of time for a range of
      commercial cements showing different viscosity-time profiles. Measurements have
      been made over a range of temperatures from 19-25 degrees C, and the results show
      a strong dependence of rate of viscosity rise on temperature. Viscoelastic
      parameters, such as storage modulus, loss modulus and phase angle have been
      obtained and show the change from primarily viscous to elastic behaviour as the
      cements set. It is suggested that these parameters more completely describe the
      rheological behaviour of bone cements than viscosity alone and may provide a
      better measure of handling and setting characteristics.

PMID- 11575476
TI  - Stearyl poly(ethylene oxide) grafted surfaces for preferential adsorption of
      albumin.
AB  - An ideal surface for many biomedical applications would resist non-specific
      protein adsorption while at the same time triggering a specific biological
      pathway. Based on the approach of selectively binding albumin to free fatty
      acids, stearyl groups were immobilized onto poly(styrene) backbone via
      poly(ethylene oxide) side chains. X-ray photoelectron spectroscopy (XPS) analysis
      indicates substantial surface enrichment of the stearyl poly(ethylene oxide)
      (SPEO). In an aqueous environment, the surface rearrangement is limited, as
      proved by dynamic contact angle tests. The comb-like copolymer presents a special
      hydrophobic surface with high SPEO surface density, which may be due to the 'tail
      like' SPEO architecture at the copolymer/water interface. Protein adsorption
      tests confirm that the comb-like surfaces adsorb high levels of albumin and
      resist fibrinogen adsorption very significantly. The surfaces prepared in this
      research attract and reversibly bind albumin due to the synergistic action of the
      PEO chains and the stearyl end groups.

PMID- 11575477
TI  - Hydrolytic degradation of poly(carbonate)-urethanes by monocyte-derived
      macrophages.
AB  - Polycarbonate (PCN)-based polyurethanes (PCNU) are rapidly becoming the chosen
      polyurethane (PU) for long-term implantation since they have shown decreased
      susceptibility to oxidation. However, monocyte-derived macrophages (MDM), the
      cell implicated in biodegradation, also contain hydrolytic activities. Hence, in
      this study, an activated human MDM cell system was used to assess the
      biostability of a PCNU, synthesized with 14C-hexane diisocyanate (HDI) and
      butanediol (BD), previously shown to be susceptible to hydrolysis by cholesterol
      esterase (CE). Monocytes, isolated from whole blood and cultured for 14 days on
      polystyrene (PS) to mature MDM, were gently trypsinized and seeded onto 14C-PCNU.
      Radiolabel release and esterase activity, as measured with p-nitrophenylbutyrate,
      increased for almost 2 weeks. At 1 week, the increase in radiolabel release and
      esterase activity were diminished by more than 50% when the protein synthesis
      inhibitor, cycloheximide, or the serine esterase/protease inhibitor,
      phenylmethylsulfonylfluoride was added to the medium. This strongly suggests that
      in part, it was MDM esterase activity which contributed to the PU degradation. In
      an effort to simulate the potential combination of oxidative and hydrolytic
      activities of inflammatory cells. 14C-PCNU was exposed to HOCl and then CE.
      Interestingly, the release of radiolabeled products by CE was significantly
      inhibited by the pre-treatment of PCNU with HOCl. The results of this study show
      that while the co-existing roles of oxidation and hydrolysis in the
      biodegradation of PCNUs remains to be elucidated, a clear relationship is drawn
      for PCNU degradation to the hydrolytic degradative activities which increase in
      MDM during differentiation from monocytes, and during activation in the chronic
      phase of the inflammatory response.

PMID- 11575478
TI  - Amphiphilic poly-N-vinylpyrrolidones: synthesis, properties and liposome surface
      modification.
AB  - Certain amphiphilic water-soluble polymers including amphiphilic derivatives of
      polyvinyl pyrrolidone (PVP) were found to be efficient steric protectors for
      liposomes in vivo. In this study, we have tried to develop synthetic pathways for
      preparing amphiphilic PVP and to investigate the influence of the
      hydrophilic/hydrophobic blocks on some properties of resulting polymers and
      polymer-coated liposomes. To prepare amphiphilic PVP with the end stearyl (S) or
      palmityl (P) residues, amino- and carboxy-terminated PVP derivatives were first
      synthesized by the free-radical polymerization of vinyl pyrrolidone in the
      presence of amino- or carboxy-mercaptans as chain transfer agents, and then
      modified by interaction of amino-PVP with stearoyl chloride or palmitoyl
      chloride, or by dicyclohexyl carbodiimide coupling of stearylamine with carboxy
      PVP. ESR-spectra of the hydrophobic spin-probe, nitroxyl radical N-oxyl-2-hexyl-2
      (10-methoxycarbonyl)decyl-4,4'-dimethyl oxazoline, in the presence of amphiphilic
      PVP demonstrated good accessibility of terminal P- and S-groups for the
      interaction with other hydrophobic ligands. Spontaneous micellization and low CMC
      values (in a low micromolar range) were found for amphiphilic PVP derivatives
      using the pyrene method. In general, S-PVP forms more stable micelles than P-PVP
      (at similar MW, CMC values for S-PVP are lower than for P-PVP). It was found that
      amphiphilic PVP incorporated into negatively charged liposomes effectively
      prevents polycation(poly-ethylpyridinium-4-vinylchloride)-induced liposome
      aggregation, completely abolishing it at ca. 10 mol% polymer content in
      liposomes. Additionally, the liposome-incorporated PVP prevents the fluorescence
      quenching of the membrane-incorporated hydrophobic fluorescent label [N-(4
      fluoresceinthiocarbamoyl)dipalmitoyl-PE] by the free polycation. PVP-modified
      liposomes were loaded with a self-quenching concentration of carboxyfluorescein,
      and their destabilization in the presence of mouse serum was investigated
      following the release of free dye. Amphiphilic PVP with MW between 1,500 and
      8,000 provides good steric protection for liposomes. The degree of this
      protection depends on both polymer concentration and molecular size of the PVP
      block.

PMID- 11575479
TI  - Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and
      proteolytically degradable domains: synthetic ECM analogs for tissue engineering.
AB  - Photopolymerizable polyethylene glycol (PEG) derivatives have been investigated
      as hydrogel tissue engineering scaffolds. These materials have been modified with
      bioactive peptides in order to create materials that mimic some of the properties
      of the natural extracellular matrix (ECM). The PEG derivatives with
      proteolytically degradable peptides in their backbone have been used to form
      hydrogels that are degraded by enzymes involved in cell migration, such as
      collagenase and elastase. Cell adhesive peptides, such as the peptide RGD, have
      been grafted into photopolymerized hydrogels to achieve biospecific cell
      adhesion. Cells seeded homogeneously in the hydrogels during photopolymerization
      remain viable, proliferate, and produce ECM proteins. Cells can also migrate
      through hydrogels that contain both proteolytically degradable and cell adhesive
      peptides. The biological activities of these materials can be tailored to meet
      the requirements of a given tissue engineering application by creating a mixture
      of various bioactive PEG derivatives prior to photopolymerization.

PMID- 11575481
TI  - Biomechanical properties in titanium implants with integrated maintenance free
      shock absorbing elements.
AB  - Good functional properties are essential in dental implantology. Bio-kinetic
      elements are imitating dental resilience. In this study a new kind of implants
      with maintenance free shock absorbing elements will be introduced and their bio
      mechanic properties reported. The mobile implant (SIS Inc., Klagenfurt, Austria)
      is a self-cutting conical screw implant with an integrated bio-kinetic element.
      The shock absorber is a central part of the implant and a titanium ring closes
      the shock absorbing unit within the implant. The resilience of the implant was
      tested by axial and horizontal loading in a special testing unit. Furthermore, a
      survival test of the elastic titanium ring in the most exposed cervical part of
      the implant was performed. The region was examined by electron microscopy after
      12 million movements in the axial and horizontal direction. A progressive shock
      absorption was registered during horizontal and axial movements. The maximum
      movements were 0.06 mm in the axial and 0.16 mm in the horizontal direction.
      There were seen no signs of material destruction in the electron microscopic
      analysis. A maintenance-free bio-kinetic implant with progressive shock absorbing
      qualities was registered.

PMID- 11575480
TI  - Intracellular delivery mediated by an ethosomal carrier.
AB  - The goal of this work was to investigate the efficiency of transcellular delivery
      into Swiss albino mice 3T3 fibroblasts of molecules with various physico-chemical
      characteristics from ethosomes, phospholipid vesicular carriers containing
      ethanol. The probes chosen were: 4-(4-diethylamino) styryl-N-methylpyridinium
      iodide (D-289), rhodamine red dihexadecanoylglycerophosphoethanolamine (RR) and
      fluorescent phosphatidylcholine (PC*). The penetration of these fluorescent
      probes into fibroblasts and nude mice skin was examined by CLSM and FACS. CLSM
      micrographs showed that ethosomes facilitated the penetration of all probes into
      the cells, as evident from the high-intensity fluorescence. In comparison, when
      incorporated in hydroethanolic solution or classic liposomes, almost no
      fluorescence was detected. The intracellular presence of each of the three probes
      tested, was evident after 3 min of incubation. Furthermore, with ethosomal D-289,
      fluorescence was also seen in the fibroblast nucleus. Enhanced delivery of
      molecules from the ethosomal carrier was also observed in permeation experiments
      with the hydrophilic calcein and lypophilic RR to whole nude mouse skin. Calcein
      penetrated the skin to a depth of 160, 80 and 60 microm from ethosomes,
      hydroethanolic solution and liposomes, respectively. Maximum fluorescence
      intensities measured for RR delivered from ethosomes, hydroethanolic solution and
      liposomes were 150, 40 and 20 AU, respectively. Fibroblast viability tests showed
      that the ethosomal carrier is not toxic to the cultured cells.

PMID- 11575482
TI  - In vitro study of the effect of titanium on porphyromonas gingivalis in the
      presence of metronidazole and spiramycin.
AB  - Septic peri-implantitis is the main clinical complication encountered following
      the insertion of titanium implants. It may be resistant to conventional
      antibiotic treatments. Reports in the literature about antibiotic behavior in the
      presence of titanium remain controversial. They vary from a bacteriostat to a
      decreased effect of antibiotic. This study examined, in vitro, the viability of
      Porphyromonas gingivalis, frequently associated with periodontal diseases, in the
      presence of titanium and antibiotics (spiramycin and metronidazole alone or in
      combination). Viability of P. gingivalis was determined, versus a standard curve
      using the Live/dead Baclight Bacteria Viability Kit on 96 well microplates. The
      results of 48 experiments (60 measurements each) were compiled in a database and
      compared to each other using the chi2p < 0.05 test. When used alone, titanium
      enhanced bacterial growth as the nickel-chrome control. However, when titanium
      was used in the presence of antibiotics, antibiotics kept their own effects. Even
      more, titanium was shown to potentialize the effect of metronidazole. The
      strengthening of effectiveness of metronidazole by titanium may be due to the
      oxidation potential of the metal. This chemical property could explain the
      conflicting data reported in the literature.

PMID- 11575483
TI  - Characterization of poly(L-lactic acid) microspheres loaded with holmium
      acetylacetonate.
AB  - Holmium-loaded PLLA microspheres are useful systems in radioembolization therapy
      of liver metastases because of their low density, biodegradability and favourable
      radiation characteristics. Neutron activated Ho-loaded microspheres showed a
      surprisingly low release of the relatively small holmium complex. In this paper
      factors responsible for this behaviour are investigated, in particular by the use
      of differential scanning calorimetry, scanning electron microscopy, infrared
      spectroscopy and X-ray diffraction. The holmium complex is soluble in PLLA up to
      8% in films and 17% in microspheres. Interactions between carbonyl groups of
      PLLA, and the Ho-ion in the HoAcAc complex, explain very satisfactorily the high
      stability of holmium-loaded microspheres.

PMID- 11575484
TI  - Effect of written and computerized decision support aids for the U.S. Agency for
      Health Care Policy and Research depression guidelines on the evaluation of
      hypothetical clinical scenarios.
AB  - OBJECTIVE: The objective of this study was to compare the effects of written and
      computerized decision support aids (DSAs) based on U.S. Agency for Health Care
      Policy and Research depression guidelines. METHODS: Fifty-six internal medicine
      residents were randomized to evaluate clinical scenarios using either a written
      or a computerized DSA after first assessing scenarios without a DSA. The paired
      difference between aided and unaided scores was determined for diagnostic
      accuracy, treatment selection, severity and subtype classification, antipsychotic
      use, and mental health consultations. RESULTS: Diagnostic accuracy with the
      written DSA increased from 64% to 73%, and with the computerized DSA decreased
      from 67% to 64% (P=0.0065). Residents using the computerized DSA (vs. no DSA)
      requested fewer consultations (65% vs. 52%, P=0.028). In post hoc analysis, the
      written DSA increased sensitivity (66% to 89%, P<0.001) and the computerized DSA
      improved specificity (66% to 86%, P=0.0020) but reduced sensitivity (67% to 49%,
      P = 0.011). CONCLUSIONS: A written DSA improved diagnostic accuracy, whereas a
      computerized DSA did not. However, the computerized DSA improved specificity and
      reduced mental health consultations.

PMID- 11575485
TI  - Cost-effectiveness of harm reduction in preventing hepatitis C among injection
      drug users.
AB  - OBJECTIVES: Hepatitis C (HCV) has emerged as a major epidemic among injection
      drug users (IDUs), with observed prevalence exceeding 70% in many American and
      European cities. This article explores the potential of syringe exchange programs
      (SEPs) to reduce HCV incidence and prevalence. DESIGN: A random-mixing
      epidemiological model is used to examine the potential impact of harm reduction
      interventions. METHODS: Steady-state analysis is used to scrutinize the impact of
      SEP on HCV incidence and prevalence and to examine the accuracy of short-term
      incidence analysis in predicting long-run program effects. RESULTS: SEP is
      predicted to have little impact on HCV incidence and prevalence within realistic
      populations of IDUs. CONCLUSIONS: Short-term incidence analysis substantially
      overstates SEP effectiveness and cost-effectiveness in preventing HCV. More
      comprehensive harm reduction models, coupled with referral of active IDUs to
      treatment, must complement syringe exchange to successfully contain highly
      infectious blood-borne diseases.

PMID- 11575486
TI  - Identifying diagnostic errors with induced decision trees.
AB  - OBJECTIVE: The purpose of this article is to compare the diagnostic accuracy of
      induced decision trees with that of pruned neural networks and to improve the
      accuracy and interpretation of breast cancer diagnosis from readings of thin
      needle aspirate by identifying cases likely to be misclassified by induced
      decision rules. METHOD: Using an online database consisting of 699 cases of
      suspected breast cancer and their corresponding readings of fine-needle aspirate,
      decision trees were induced from half of the cases, randomly selected. Accuracy
      was determined for the remaining cases in successive partitions. The pattern of
      errors in the multiple decision trees was examined. A smaller data set was
      created with 2 classes: (1) correctly classified and (2) misclassified by a
      decision tree, rather than the original benign and malignant classes. From this
      data set, decision trees that describe the misclassified cases were induced.
      RESULTS: Larger, less severely pruned decision trees were more accurate in breast
      cancer diagnosis for both training and test data. The accuracy of the induced
      decision trees exceeded that reported for the smaller pruned neural networks.
      Combining classifications from 2 trees was effective in identifying malignancies
      missed by a single tree. Induced decision trees were able to identify patterns
      associated with misclassified cases, but the identification of errors inductively
      did not improve the overall error rate. CONCLUSION: In this application, a model
      that is too compact identifies fewer cases of the minority class, malignancy. New
      methods that combine models and examine classification errors can improve
      diagnosis by identifying more malignancies and by describing ambiguous cases.

PMID- 11575487
TI  - The beguiling pursuit of more information.
AB  - BACKGROUND: The authors tested whether clinicians make different decisions if
      they pursue information than if they receive the same information from the start.
      METHODS: Three groups of clinicians participated (N=1206): dialysis nurses
      (n=171), practicing urologists (n=461), and academic physicians (n=574). Surveys
      were sent to each group containing medical scenarios formulated in 1 of 2
      versions. The simple version of each scenario presented a choice between 2
      options. The search version presented the same choice but only after some
      information had been missing and subsequently obtained. The 2 versions otherwise
      contained identical data and were randomly assigned. RESULTS: In one scenario
      involving a personal choice about kidney donation, more dialysis nurses were
      willing to donate when they first decided to be tested for compatibility and were
      found suitable than when theyknew they were suitable from the start (65% vs. 44%,
      P= 0.007). Similar discrepancies were found in decisions made by practicing
      urologists concerning surgery for a patient with prostate cancer and in decisions
      of academic physicians considering emergency management for a patient with acute
      chest pain. CONCLUSIONS: The pursuit of information can increase its salience and
      cause clinicians to assign more importance to the information than if the same
      information was immediately available. An awareness of this cognitive bias may
      lead to improved decision making in difficult medical situations.

PMID- 11575488
TI  - Assessing values for health: numeracy matters.
AB  - BACKGROUND: Patients' values are fundamental to decision models, cost
      effectiveness analyses, and pharmacoeconomic analyses. The standard methods used
      to assess how patients value different health states are inherently quantitative.
      People without strong quantitative skills (i.e., low numeracy) may not be able to
      complete these tasks in a meaningful way. METHODS: To determine whether the
      validity of utility assessments depends on the respondent's level of numeracy,
      the authors conducted in-person interviews and written surveys and assessed
      utility for the current health for 96 women volunteers. Numeracy was measured
      using a previously validated 3-item scale. The authors examined the correlation
      between self-reported health and utility for current health (assessed using the
      standard gamble, time trade-off, and visual analog techniques) across levels of
      numeracy. For half of the women, the authors also assessed standard gamble
      utility for 3 imagined health states (breast cancer, heart disease, and
      osteoporosis) and asked how much the women feared each disease. RESULTS:
      Respondent ages ranged from 50 to 79 years (mean = 63), all were high school
      graduates, and 52% had a college or postgraduate degree. Twenty-six percent
      answered 0 or only 1 of the numeracy questions correctly, 37% answered 2
      correctly, and 37% answered all 3 correctly. Among women with the lowest level of
      numeracy, the correlation between utility for current health and self-reported
      health was in the wrong direction (i.e., worse health valued higher than better
      health): for standard gamble, Spearman r=-0.16, P = 0.44;for time trade-off,
      Spearman r=-0.13, P=0.54. Among the most numerate women, the authors observed a
      fair to moderate positive correlation with both standard gamble (Spearman r=0.22,
      P=0.19) and time trade-off (Spearman r=0.50, P=0.002). In contrast, using the
      visual analog scale, the authors observed a substantial correlation in the
      expected direction at all levels of numeracy (Spearman r= 0.82, 0.50, and 0.60
      for women answering 0-1, 2, and 3 numeracy questions, respectively; all Ps < or =
      0.003). With regard to the imagined health states, the most feared disease had
      the lowest utility for 35% of the women with the lowest numeracy compared to 76%
      of the women with the highest numeracy (P=0.03). CONCLUSIONS: The validity of
      standard utility assessments is related to the subject's facility with numbers.
      Limited numeracy may be an important barrier to meaningfully assessing patients'
      values using the standard gamble and time trade-off techniques.

PMID- 11575489
TI  - Optimal investment in a portfolio of HIV prevention programs.
AB  - OBJECTIVES: In this article, the authors determine the optimal allocation of HIV
      prevention funds and investigate the impact of different allocation methods on
      health outcomes. METHODS: The authors present a resource allocation model that
      can be used to determine the allocation of HIV prevention funds that maximizes
      quality-adjusted life years (or life years) gained or HIV infections averted in a
      population over a specified time horizon. They apply the model to determine the
      allocation of a limited budget among 3 types of HIV prevention programs in a
      population of injection drug users and nonusers: needle exchange programs,
      methadone maintenance treatment, and condom availability programs. For each
      prevention program, the authors estimate a production function that relates the
      amount invested to the associated change in risky behavior. RESULTS: The authors
      determine the optimal allocation of funds for both objective functions for a high
      prevalence population and a low-prevalence population. They also consider the
      allocation of funds under several common rules of thumb that are used to allocate
      HIV prevention resources. It is shown that simpler allocation methods (e.g.,
      allocation based on HIV incidence or notions of equity among population groups)
      may lead to alloctions that do not yield the maximum health benefit. CONCLUSIONS:
      The optimal allocation of HIV prevention funds in a population depends on HIV
      prevalence and incidence, the objective function, the production functions for
      the prevention programs, and other factors. Consideration of cost, equity, and
      social and political norms may be important when allocating HIV prevention funds.
      The model presented in this article can help decision makers determine the health
      consequences of different allocations of funds.

PMID- 11575490
TI  - Parametric three-way receiver operating characteristic surface analysis using
      mathematica.
AB  - Three-way receiver operating characteristic (ROC) surface analysis involves the
      calculation of a volume under an ROC surface (VUS), which is a measure of
      discriminatory accuracy of 2 diagnostic tests for 3 diseases. Nonparametric
      methods for calculating VUS and its standard error have been developed. The
      author presents the code for roc3D, a Mathematica computer program for performing
      parametric ROC surface analysis. roc3D calculates VUS assuming a multinormal
      distribution of test results in the 3 diseased populations, provides user
      specified pointwise confidence limits for VUS, and displays a 3-dimensional plot
      of the ROC surface. Limitations of the roc3D program are discussed.

PMID- 11575491
TI  - Law and ethics.

PMID- 11575492
TI  - Area under the ROC curve for a binary diagnostic test.

PMID- 11575493
TI  - A common on "response shift and adaptation in chronically ill patients" by
      Postulart and Adang.

PMID- 11575494
TI  - Do mycoplasmas cause human cancer?
AB  - A linkage between mycoplasmas and malignancy was mainly proposed in the 1960s
      when human-associated mycoplasmas were becoming of interest given the novel
      characterization of the human respiratory pathogen Mycoplasma pneumoniae.
      Associations with leukemia and other malignancies, however, were largely ascribed
      to tissue-culture contamination, which is now recognized as a significant
      potential problem in molecular biology circles. A few epidemiological studies,
      however, continue to raise concern over such a linkage. As well, in vitro data
      have demonstrated the potential for some mycoplasmas to induce karyotypic changes
      and malignant transformation during chronic tissue-culture infestation. As
      cellular and molecular mechanisms for such transformation become studied, a
      resurgence of interest in this area is inevitable. A role for mycoplasmas in
      malignancy of any sort is conjectural, but there remains a need to continue with
      focussed epidemiological and laboratory investigations.

PMID- 11575495
TI  - Involvement of gacS and rpoS in enhancement of the plant growth-promoting
      capabilities of Enterobacter cloacae CAL2 and UW4.
AB  - The plant growth-promoting bacteria Enterobacter cloacae CAL2 and UW4 were
      genetically transformed with a multicopy plasmid containing an rpoS or gacS gene
      from Pseudomonas fluorescens. The transformed strains were compared with the
      nontransformed strains for growth, indoleacetic acid (IAA) production, antibiotic
      production, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity,
      siderophore production, cell morphology, and the ability to promote canola root
      elongation. All transformed strains had a longer lag phase, were slower in
      reaching stationary phase, and attained a higher cell density than the
      nontransformed strains. Transformation resulted in cells that were significantly
      shorter than the nontransformed cells. The transformed strains also produced
      significantly more IAA than the nontransformed strains. Introduction of rpoS or
      gacS from Pseudomonas fluorescens was associated with a reduction in the
      production of both antibiotics, 2,4-diacetylphloroglucinol and mono
      acetylphloroglucinol, produced by Enterobacter cloacae CAL2. With Enterobacter
      cloacae CAL2, plasmid-borne rpoS, but not gacS, increased the level of ACC
      deaminase activity, while introduction of rpoS in Enterobacter cloacae UW4 caused
      a decrease in ACC deaminase activity. Neither gacS nor rpoS significantly
      affected the level of siderophores synthesized by either bacterial strain.
      Overproduction of either GacA or RpoS in Enterobacter cloacae CAL2 resulted in a
      significant increase in the root lengths of canola seedlings when seeds were
      treated with the bacteria, and overproduction of RpoS caused an increase in
      canola shoot as well as root lengths.

PMID- 11575496
TI  - Sterol composition of itraconazole-resistant and itraconazole-susceptible
      isolates of Aspergillus fumigatus.
AB  - Sterol composition of four clinical isolates of Aspergillus fumigatus resistant
      to itraconazole was determined by gas chromatography--mass spectrometry and
      compared with that of four susceptible strains. For all strains, the major sterol
      was ergosterol. Sterol compositions were qualitatively and quantitatively similar
      for the resistant and susceptible strains. These results suggest that
      itraconazole resistance is not related, for the strains studied, to alterations
      in the ergosterol synthesis pathway.

PMID- 11575497
TI  - Isolation and characterization of a chromosomally encoded disulphide
      oxidoreductase from Salmonella enterica serovar Typhimurium.
AB  - In this study, the chromosomally encoded disulphide oxidoreductase dsbA from
      Salmonella typhimurium was cloned and characterized. A survey of a number of
      serovars of Salmonella subspecies I showed that dsbA is highly conserved in most,
      but not all members of this subclass of Salmonella species. Using motility, beta
      galactosidase, and alkaline phosphatase assays as indirect indicators of
      disulphide oxidoreductase activity, we demonstrated that DsbA from S. typhimurium
      LT2 can only partially complement an Escherichia coli dsbA-null strain. This is
      surprising considering the high degree of conservation between these two DsbA
      proteins (87% amino acid identity). To determine the contribution of DsbA to the
      proper folding and assembly of proteins of S. typhimurium, deletion mutants were
      created in the avirulent strain LT2 and in the virulent strain SL1344. These null
      alleles were constructed by partial deletion of the dsbA-coding region and then
      insertion of an antibiotic resistance marker in the gene. Mutants no longer
      expressing a functional disulphide oxidoreductase exhibit pleitropic effects,
      including an increase in colony mucoidy, a dramatic decrease in motility, and an
      increased susceptibility to the cationic peptide protamine sulphate. The
      disruption of disulphide bond formation was also shown to specifically affect the
      stability of several proteins secreted into the extracellular environment.

PMID- 11575498
TI  - Precise excision of bacteriophage Mu DNA.
AB  - The temperate bacteriophage Mu is a transposable element that can integrate
      randomly into bacterial DNA, thereby creating mutations. Mutants due to an
      integrated Mu prophage do not give rise to revertants, as if Mu, unlike other
      transposable elements, were unable to excise precisely. In the present work,
      starting with a lacZ::Muc62(Ts) strain unable to form Lac+ colonies, we cloned a
      lacZ+ gene in vivo on a mini-Mu plasmid, under conditions of prophage induction.
      In all lac+ plasmids recovered, the wild-type sequence was restored in the region
      where the Mu prophage had been integrated. The recovery of lacZ+ genes shows that
      precise excision of Mu does indeed take place; the absence of Lac+ colonies
      suggests that precise excision events are systematically associated with loss of
      colony-forming ability.

PMID- 11575499
TI  - Extrusion of actin-positive strands from Hep-2 and Int 407 cells caused by outer
      membrane preparations of enteropathogenic Escherichia coil and specific
      attachment of wild type bacteria to the strands.
AB  - Enteropathogenic Escherichia coli (EPEC) causes persistent infantile diarrhoea.
      This nontoxigenic E. coli exhibits a complicated pathogenic mechanism in which
      its outer membrane proteins and type III secretory proteins damage intestinal
      epithelium and cause diarrhoea. In accordance with this, our previous study using
      HEp-2 cells demonstrated cytopathic effects caused by cell-free outer membrane
      preparations of EPEC. In this study, we report the extrusion of actin-positive
      strands from HEp-2 and Int 407 cells when treated with outer membrane
      preparations. An interesting observation of this work, perhaps relevant to the
      characteristic localized three-dimensional colony formation of EPEC, is the
      attachment of a wild type EPEC strain to these actin-positive strands.

PMID- 11575500
TI  - Reduction of linoleic acid inhibition in production of conjugated linoleic acid
      by Propionibacterium freudenreichii ssp. shermanii.
AB  - A method for the production of conjugated linoleic acid (CLA) from linoleic acid
      (LA) using growing cultures of Propionibacterium freudenreichii ssp. shermanii JS
      was developed. The growth inhibitory effect of LA was eliminated by dispersing it
      in a sufficient concentration of polyoxyethylene sorbitan monooleate detergent.
      For the whey permeate medium used, the optimum LA:detergent ratio was 1:15 (w/w).
      As a result, the cultures tolerated at least 1000 microg x mL(-1) LA, which was
      converted to CLA with 57%-87% efficiency. The cis-9, trans-11 and trans-9, cis-11
      isomers constituted 85%-90% of the CLA produced. The feasibility of the method
      was demonstrated also in de Man Rogosa-Sharpe (MRS) broth.

PMID- 11575501
TI  - Characterization of the interaction between the dark septate fungus Phialocephala
      fortinii and Asparagus officinalis roots.
AB  - Phialocephala fortinii Wang & Wilcox is a member of root-inhabiting fungi known
      collectively as dark septate endophytes (DSE). Although very common and
      distributed worldwide, few studies have documented their interaction with roots
      on a structural basis. The objective of this study was to determine the early
      colonization events and formation of microsclerotia of P. fortinii in roots of
      Asparagus officinalis L., a species known to have DSE. A loose network of hyphae
      accumulated at the root surface, and coils formed around root hairs and external
      to epidermal cells overlying short cells of the dimorphic, suberized exodermis.
      Root penetration occurred via swollen, appressorium-like structures into
      epidermal cells where coiling of hyphae occurred along the periphery of the
      cells. Hyphae penetrated from the epidermis into short exodermal cells and from
      these into cortical cells. Hyphae colonized the cortex up to the endodermis and
      sometimes entered the vascular cylinder. Some root tips were colonized as well.
      Microsclerotia in epidermal and exodermal short cells accumulated glycogen,
      protein, and polyphosphate. Energy-dispersive X-ray spectroscopy on distinct
      bodies visible in microsclerotial hyphae revealed high levels of phosphorus.

PMID- 11575502
TI  - The effects of sequential inoculation of mixed rumen protozoa on the degradation
      of orchard grass cell walls by anaerobic fungus Anaeromyces mucronatus 543.
AB  - The effects of protozoa on the degradation of plant cell walls (CW) during
      different growth stages of the fungus Anaeromyces mucronatus have been
      investigated. Since fungi show a marked lag in their in vitro cultures and many
      protozoa rapidly die during a prolonged incubation time, the effects of protozoa
      may vary according to the growth phase of the fungi. Therefore, the approach
      adopted was (i) to inoculate CW with fungus monoculture, (ii) to inoculate CW
      with fungus-protozoa coculture, or (iii) to sequentially inoculate fungal
      cultures that had been grown in CW for 24 (initial stage of growth), 48, and 72 h
      (late stage of growth) with mixed protozoa. When a fungus was associated with
      protozoa, a growth phase dependent effect was observed. Ruminal protozoa
      adversely affected the growth and activity when introduced in the initial growth
      stage of A. mucronatus, but a synergetic interaction was detected when added to
      late growth stage cultures. Although there is no immediate explanation for these
      results, the data suggested that protozoa can engulf the fungal zoospores, which
      are in ruminal fluids and (or) attached to small feed particles, but cannot
      engulf the fungal thallus that is tightly attached to feed particles by a
      rhizoidal system. Our data indicated that the protozoa did not influence
      cellulolysis by the fungi in exponential and (or) stationary phase, but they had
      a marked inhibitory effect on fungi that were in lag phase. Inhibition during lag
      phase could result from the protozoal predation of fungal zoospores that had
      failed to attach to substrates.

PMID- 11575503
TI  - The occurrence of cyanobacteria in pulp and paper waste-treatment systems.
AB  - Pulp and paper secondary waste-treatment systems in Brazil, Canada, New Zealand,
      and the U.S.A. contained dynamic cyanobacterial communities, some of which
      exceeded heterotrophic bacterial biomass. No other viable photoautotrophic
      populations were detected in the ponds. Regardless of geographical location,
      Oscillatoriales including Phormidium, Geitlerinema, and Pseudanabaena were the
      dominant taxa. As well, Chroococcus (Chroococcales) was an important genus in
      Brazil and New Zealand. The possible impact of cyanobacteria on waste-treatment
      efficiency deserves further study given their large biomass and diverse metabolic
      characteristics.

PMID- 11575504
TI  - Physicochemical properties of a novel alpha-L-arabinofuranosidase from Rhizomucor
      pusillus HHT-1.
AB  - The zygomycete fungus Rhizomucor pusillus HHT-1, cultured on L(+)arabinose as a
      sole carbon source, produced extracellular alpha-L-arabinofuranosidase. The
      enzyme was purified by (NH4)2SO4 fractionation, gel filtration, and ion exchange
      chromatography. The molecular mass of this monomeric enzyme was 88 kDa. The
      native enzyme had a pI of 4.2 and displayed a pH optimum and stability of 4.0 and
      7.0-10.0, respectively. The temperature optimum was 65 degrees C, and it was
      stable up to 70 degrees C. The Km and Vmax for p-nitrophenyl alpha-L
      arabinofuranoside were 0.59 mM and 387 micromol x min(-1) x mg(-1) protein,
      respectively. Activity was not stimulated by metal cofactors. The N-terminal
      amino acid sequence did not show any similarity to other arabinofuranosidases.
      Higher hydrolytic activity was recorded with pnitrophenyl alpha-L
      arabinofuranoside, arabinotriose, and sugar beet arabinan; lower hydrolytic
      activity was recorded with oat-spelt xylan and arabinogalactan, indicating
      specificity for the low molecular mass L(+)-arabinose containing oligosaccharides
      with furanoside configuration.

PMID- 11575505
TI  - Influence of the zinc hyperaccumulator Thlaspi caerulescens J. & C. Presl. and
      the nonmetal accumulator Trifolium pratense L. on soil microbial populations.
AB  - Metal hyperaccumulator plants like Thlaspi caerulescens J. & C. Presl. are used
      for phytoremediation of contaminated soils. Since little is known about the
      rhizosphere of hyperaccumulators, the influence of T. caerulescens was compared
      with the effects of Trifolium pratense L. on soil microbes. High- and low-metal
      soils were collected near a zinc smelter in Palmerton, Penn. Soil pH was adjusted
      to 5.8 and 6.8 by the addition of Ca(OH)2. Liming increased bacterial populations
      and decreased metal toxicity to levels allowing growth of both plants. The
      effects of the plants on total (culturable) bacteria, total fungi, as well as
      cadmium- and zinc-resistant populations were assessed in nonrhizosphere and
      rhizosphere soil. Both plants increased microbial populations in rhizosphere soil
      compared with nonrhizosphere soil. Microbial populations were higher in soils
      planted with T. pratense, but higher ratios of metal-resistant bacteria were
      found in the presence of T. caerulescens. We hypothesize that T. caerutescens
      acidifies its rhizosphere. Soil acidification in the rhizosphere of T.
      caerulescens would affect metal uptake by increasing available metals around the
      roots and consequently, increase the selection for metal-resistant bacteria. Soil
      acidification may be part of the hyperaccumulation process enhancing metal uptake
      from soil.

PMID- 11575506
TI  - Effects of antecedent fermentative and respiratory growth on the detection of
      chloramine-stressed Escherichia coil and Salmonella typhimurium.
AB  - In vitro laboratory studies were performed to assess the effects of antecedent
      growth conditions on the recovery of Escherichia coli ATCC 25922 and Salmonella
      typhimurium ATCC 14028 following chloramine disinfection. Six- and 18-h cultures
      of each organism were grown under aerobic, fermentative, and nitrate-reducing
      conditions prior to disinfection. At predetermined time intervals during a 10-min
      exposure to chloramine, survivors were surface plated on nonselective recovery
      media to determine C(n)t values. It was observed that nitrate-reducing growth
      predisposed the test organisms towards an increased sensitivity to chloramine
      stress over cells grown under fermentation or aerobic conditions (p < 0.01).

PMID- 11575507
TI  - Detection of Aeromonas hydrophila in a drinking-water distribution system: a
      field and pilot study.
AB  - A 16-month study was conducted on the presence of Aeromonas hydrophila in
      drinking water in Indiana, U.S.A. Enumeration was conducted in source water, in
      various sites within a water treatment plant, and in the distribution system in
      both bulk water and biofilm, as well as in a simulated (annular reactors)
      drinking-water distribution system. Presumptive Aeromonas spp. counts on source
      waters regularly approached 10(3)-10(4) CFU/100 mL, during summer months and
      granular activated carbon - filtered water counts ranged from <1 to 490 CFU/100
      mL. In source water, presumptive Aeromonas levels were related to water
      temperature. Aeromonas hydrophila was never detected in the treatment plant
      effluent or distributed bulk water, showing disinfectant efficiency on suspended
      bacteria; however, isolates of A. hydrophila were identified in 7.7% of the
      biofilm samples, indicating a potential for regrowth and contamination of
      drinking-water distribution systems.

PMID- 11575508
TI  - A procedure for quantifying adhesion of conidia of Botrytis cinerea to the skin
      of apple fruit.
AB  - Ultrasonication was evaluated as a nonchemical means to quantitatively remove
      conidia of Botrytis cinerea from the skin of Golden Delicious apple (Malus
      domestica Borkh.) fruit. A probe immersed in a suspension of conidia and
      generating 20 kHz at 150 W for 30- or 60-s pulses destroyed 13.3% or 29% of
      conidia, respectively. Destruction at 150 W for 10 s or at 30-120 W for up to 60
      s was <2%. The procedure for quantifying adhesion of conidia to the skin of fruit
      consisted of pipetting a 50-microL water droplet containing 5 x 10(4) conidia
      onto the skinside of a slice of fruit, incubating the slices inside sealed 500
      cm3 glass jars, excising a 1 cm diameter piece of skin bearing the droplet, and
      sonicating the skin in 8 mL of ice-cold water at 150 W for 10 s. The skin was
      removed, the suspension was centrifuged at 1250 x g for 15 min, and the
      supernatant was reduced to 1 mL by vacuum suction using a pipet. Conidia were
      stained with crystal violet and counted in a hemacytometer. Adhesion of conidia
      to skin was 3.0%, 14.6%, 20.8%, 39.4%, 57.6%, and 73.1% after 0, 2, 4, 8, 12, and
      24 h incubation, respectively. Sonication was more effective than two other
      procedures for recovery of conidia. Conidia on the skin of fruit exposed to 4
      microL of butyl acetate in the headspace of glass jars for 4 h at 23 degrees C
      increased the adhesion of conidia 107% above that for unexposed conidia.
      Sonication with a programmable power- and time-controlled probe was a simple,
      rapid, safe, and effective method for quantifying adhesion of B. cinerea conidia
      to the skin of apple fruit.

PMID- 11575509
TI  - Identification and its relation to identity development.
AB  - Two meanings of identification-as a developmental process and as a mechanism of
      defense-were investigated as they relate to identity status. Identification with
      parents was assessed by comparing participants' "ideal self" Adjective Q-sort
      (Block, 1978) with the same Q-sort done for either mother or father. Defense
      identification was assessed from TAT stories using Cramer's (1991a) Defense
      Mechanism Manual. Marcia's (1966, 1980) categories of identity status were
      determined from Mallory's (1989) prototypes based on the California Adult Q-sort
      (Block, 1961/1978). The results indicated that the four identity statuses are
      differentially predicted by parent identification, by defense identification, and
      by an interaction between the two types of identification. Further, the nature of
      these relations differs by gender. Caution should be used in applying these
      findings to other populations.

PMID- 11575510
TI  - The relation of self-esteem variability to emotion variability, mood, personality
      traits, and depressive tendencies.
AB  - The relation of self-esteem variability to personality, mood, and behavior was
      investigated. Self-esteem variability was measured by calculating the standard
      deviation of self-ratings made during a week of experience-sampling. Participants
      high in self-esteem variability were self-conscious, socially anxious, and
      avoidant of social contexts. Self-esteem variability was partially independent of
      the conceptually similar trait of affect-intensity. The contributions of the
      study to work on self-esteem stability are discussed.

PMID- 11575511
TI  - Analyses of Digman's child-personality data: derivation of Big-Five factor scores
      from each of six samples.
AB  - One of the world's richest collections of teacher descriptions of elementary
      school children was obtained by John M. Digman from 1959 to 1967 in schools on
      two Hawaiian islands. In six phases of data collection, 88 teachers described
      2,572 of their students, using one of five different sets of personality
      variables. The present report provides findings from new analyses of these
      important data, which have never before been analyzed in a comprehensive manner.
      When factors developed from carefully selected markers of the Big-Five factor
      structure were compared to those based on the total set of variables in each
      sample, the congruence between both types of factors was quite high. Attempts to
      extend the structure to 6 and 7 factors revealed no other broad factors beyond
      the Big Five in any of the 6 samples. These robust findings provide significant
      new evidence for the structure of teacher-based assessments of child personality
      attributes.

PMID- 11575512
TI  - Neuroticism and social comparison orientation as moderators of affective
      responses to social comparison at work.
AB  - In a study among 72 nurses, the affective consequences of social comparison were
      examined and related to neuroticism (N) and to social comparison orientation
      (SCO). Participants were confronted with a bogus interview with an upward versus
      a downward comparison target. Positive affect and identification were higher, and
      negative affect was lower, in the upward than in the downward comparison
      condition. Independent of their SCO, the higher individuals were in N, the less
      they identified with the upward comparison target, the more they identified with
      the downward comparison target, and the less positive affect they showed
      following confrontation with the upward comparison target. In contrast,
      independent of their level of N, the higher individuals were in SCO, the more
      negative affect they showed following confrontation with the downward comparison
      target. The effects on negative affect stayed the same when controlling for
      positive affect, and the effects on positive affect stayed the same when
      controlling for negative affect. These effects were also obtained when perceived
      direction was used as a predictor instead of the experimentally manipulated
      direction. It is concluded that, although N and SCO are correlated, these
      variables seem to have independent and distinct effects upon the responses to
      social comparison information.

PMID- 11575513
TI  - Discriminative facility and its role in the perceived quality of interactional
      experiences.
AB  - Discriminative facility refers to an individual's sensitivity to subtle cues
      about the psychological meaning of a situation. This research aimed at examining
      (a) the conceptual distinctiveness of discriminative facility, (b) the situation
      appropriate aspect of this construct, and (c) the relationship between
      discriminative facility and interpersonal experiences. Discriminative facility
      was assessed by a new measure of situation-appropriate behaviors across a variety
      of novel stressful situations. Results from study 1 showed that discriminative
      facility had weak positive relationships with cognitive complexity and
      nonsignificant relationships with self-monitoring and social desirability,
      indicating that discriminative facility is a unique construct. Results from Study
      2 revealed that higher levels of discriminative facility were associated with
      higher levels of perceived social support and a greater number of pleasant
      interpersonal events experienced, thus providing support for the theoretical
      proposition that discriminative facility is an aspect of social intelligence.

PMID- 11575514
TI  - Contemporary concepts of urinary diversion.

PMID- 11575515
TI  - Ureteroileal anastomosis in orthotopic urinary diversion: how much or how little
      is necessary?
AB  - PURPOSE: An increasing number of patients with an orthotopic neobladder and their
      expanding life expectancy necessitate an effective antireflux protection of the
      upper urinary tract. During the evolution of urinary diversion in the 20th
      century, several techniques to perform an ureteroileal anastomosis have been
      introduced. Those techniques most commonly used for orthotopic neobladders are
      discussed. MATERIALS AND METHODS: Vascularization of both the ureteral ends and
      the recipient bowel as well as a meticulous surgical technique are necessary to
      reduce the reported postoperative stricture rate, which ranges between 3% and
      30%. Variations such as preservation of additional periureteral adventitial
      tissue and its use for coverage of the ureterointestinal suture line are
      described. High-pressure urinary reflux may lead to mechanical damage of the
      renal parenchyma, whereas low-pressure occasional reflux in conjunction with
      chronic bacteriuria will lead to pyelonephritic changes and eventually
      deterioration of renal function. An intraluminal valve mechanism with increasing
      efficiency during pouch filling is clearly the most physiological form of
      antireflux mechanism. Interposition of an afferent ileal limb in addition to the
      antireflux valve seems advantageous due to the favorable vascularization in the
      dissected midureter. CONCLUSIONS: Increased life expectancy in patients with
      orthotopic neobladders will increase the number of cases where access to the
      upper urinary tract becomes necessary due to a benign or malignant disease. Any
      technique that simultaneously provides an efficient antireflux mechanism and
      facilitates retrograde manipulation of the ureters (via the pouch) will be
      greatly appreciated by both patients and treating physicians.

PMID- 11575516
TI  - Orthotopic urinary diversion with the ileal neobladder.
AB  - Orthotopic lower urinary tract reconstruction is the procedure of choice in
      appropriately selected men and women requiring cystectomy. Despite extensive
      experience with this technique, no consensus exists regarding which intestinal
      segment or reservoir configuration provides the best results. Consequently,
      various bowel segments and neobladder designs have been described. In 1988,
      Hautmann and colleagues initially described the ileal neobladder as a safe,
      reliable method of orthotopic urinary diversion. In this article, we describe our
      technique and experience with the modified ileal neobladder.

PMID- 11575517
TI  - Ureterointestinal anastomosis in continent urinary diversion: an antirefluxing
      procedure--is it necessary?

PMID- 11575518
TI  - T-mechanism applied to urinary diversion: the orthotopic T-pouch ileal neobladder
      and cutaneous double-T-pouch ileal reservoir.
AB  - PURPOSE: As the evolution of lower urinary tract reconstruction continues, newer
      and improved forms of urinary diversion have developed. Critical components of
      continent urinary reservoirs included an antireflux and continent mechanism that
      is effective, durable, easily constructed, and associated with little morbidity.
      MATERIALS AND METHODS: We describe the flap valve known as the T-mechanism as it
      applies to an afferent antireflux mechanism in an orthotopic ileal reservoir (T
      pouch) and as an antireflux and efferent continence mechanism in the continent
      cutaneous ileal reservoir (double T-pouch). CONCLUSIONS: We believe the T
      mechanism is an extremely effective and versatile flap-valve technique that can
      be easily learned and applied to the construction of continent urinary
      diversions.

PMID- 11575519
TI  - Spiral ileal neobladder substitution with orthotopic ureteral reimplantation:
      early results.
AB  - PURPOSE: The aim of this report is to present our experience with the spiral
      ileal neobladder. MATERIALS AND METHODS: From September 1996 to August 1999, 39
      patients (35 men and 4 women) underwent radical cystectomy and spiral ileal
      orthotopic substitution for muscle invasive bladder cancer. Seventy ureters in 37
      patients were reimplanted orthotopically using the nonrefluxing Ghoneim
      technique. Evaluation of these patients included video urodynamics, intravenous
      pyelogram, renal ultrasound, and patient history relating to urinary
      incontinence. RESULTS: There were no perioperative deaths. There were 8 (20.5%)
      early complications. One patient developed a small bowel anastomotic leak, and
      another patient presented with a vesicovaginal fistula repaired transabdominally.
      Of the 70 ureters reimplanted in Ghoneim fashion, 5 (7.1%) developed an
      anastomotic stricture. Three of these patients had stable hydronephrosis and were
      managed by observation alone; one stricture was treated successfully
      transurethrally with balloon dilation; and the last patient was managed with a
      percutaneous nephrostomy tube and surgical reimplantation. Urodynamics in eight
      patients revealed a Valsalva leak point pressure >50 in two patients and >100 in
      the six patients. All women experienced mild daytime and nighttime urinary
      incontinence. Ninety percent of the men were either dry or complained of mild
      daytime incontinence. No patient experienced bowel dysfunction from the ileal
      resection. CONCLUSIONS: The spiral ileal neobladder offers the potential
      advantages of construction from a relatively short bowel segment, excellent
      length for ureteral anastomosis, acceptable continence rates, and orthotopically
      reimplanted ureters, which allow transurethral upper tract access. The
      nonrefluxing ureteral anastomosis has a high stricture rate, and we currently are
      reimplanting the ureters orthopically in a nontunneled fashion.

PMID- 11575520
TI  - Male perineal sling.
AB  - PURPOSE: Postprostatectomy incontinence remains a significant problem for both
      patients and their urologists. Treatment options include placement of an
      artificial urinary sphincter or collagen injections. Many patients with only
      minimal or moderate stress incontinence after prostatectomy shy away from AUS
      placement and do not benefit from collagen injections. We evaluate the placement
      of the male perineal sling as an option in the treatment of post-prostatectomy
      stress urinary incontinence. METHODS AND MATERIALS: Ten patients had placement of
      a male perineal sling with cadaveric fascia lata. Their pre- and postoperative
      symptoms, including quality of life scores, were evaluated with a standard
      validated incontinence questionnaire. RESULTS: Preliminary results show that 70%
      of patients were dry, 10% showed improvement, and 20% were dry but had sudden
      return of their symptoms. The last two patients had pelvic x-rays which revealed
      migration of the bone anchors out of the pubic rami. All patients had improvement
      in their quality of life. Mean operative time was 30 minutes, and no operative
      complications were encountered. CONCLUSIONS: The male perineal sling is a quick
      and simple procedure in the treatment of post-prostatectomy stress urinary
      incontinence.

PMID- 11575521
TI  - Effect of prostate size and isotope selection on dosimetric quality following
      permanent seed implantation.
AB  - PURPOSE: The aim of this study was to assess retrospectively the influence of
      prostate size and the effect of isotope selection on implant quality in patients
      undergoing transperineal ultrasound-guided permanent prostate brachytherapy.
      PATIENTS AND METHODS: Two hundred forty-eight consecutive patients without prior
      transurethral resection of the prostate gland underwent permanent seed
      implantation using either iodine 125 or palladium 103 as monotherapy or a boost
      following moderate doses of external-beam radiation therapy from January 1998
      through November 1999. Postimplant dosimetry was obtained on day 0 using thin
      slice computed tomography (CT) scans. Dosimetric quality was reported in terms of
      the following parameters: D90, V100, V150, and V200, where D90 is defined as the
      minimum dose covering 90% of the prostate volume, and V100, V150, and V200 are
      defined as the percentage volume of the prostate receiving at least 100%, 150%,
      and 200% of the prescribed minimal peripheral dose (mPD), respectively. In
      addition, the urethral dose was evaluated. Preimplant prostate size was divided
      into the following categories: <20, 20-30, 30-40, 40-50, and >50 cm3. Prostate
      volume was determined via transrectal ultrasound volumetric study. In addition,
      within each of the five size categories, the effect of isotope on implant quality
      was evaluated. RESULTS: No statistically significant volume dependence in D90,
      V100, or urethral doses was discerned, whereas V150 and V200 were volume
      dependent. Between isotopes, the following differences in dosimetric quality were
      statistically significant: V100, V150, V200, and mean and medial urethral dose.
      125I implants had higher values of V100 (95% vs. 94%, p = .004) and urethral dose
      (118% vs. 110% of mPD, p < .001), and 103Pd implants had higher V150 and V200
      (57% vs. 51% and 31% vs. 22%, respectively). Only the isotopic differences in
      V200 persisted for all the volumetric subgroups. There was no significant overall
      volume dependence based on neoadjuvant hormone use or nonuse for any of the
      quality parameters analyzed. CONCLUSIONS: The most important indicators of the
      quality of dosimetric coverage, V100 and D90, were not dependent on preimplant
      prostate volume or use of neoadjuvant hormones. The mean, median, and maximum
      urethral doses also showed no dependence on prostate size. Although there were
      isotopic differences in day 0 dosimetric parameters following permanent prostate
      brachytherapy, we do not consider the magnitude of any of these differences to be
      clinically significant.

PMID- 11575522
TI  - Hypospadias repair using a modified Foley catheter (hole-end catheter).
AB  - PURPOSE: The aim of this study was to test the effectiveness of a modified Foley
      catheter for improving the results of hypospadias repair by decreasing the
      incidence of obstruction. MATERIALS AND METHODS: Seventy-two patients (age 3 to
      21 years) with variable types of hypospadias were treated. Bladder drainage was
      performed by urethral catheter insertion. The patients were divided equally into
      two groups of 36 patients each, according to the type of catheter used. In the
      first group of patients, a Foley catheter was inserted; in the second group, a
      modified Foley catheter (hole-end catheter) was introduced for urine drainage.
      RESULTS: Fourteen patients (19.4%) required secondary surgical repair: 8 (22.2%)
      in the first group and 6 (16.7%) in the second group. The rate of complications
      was lower in the second group than in the first group (25% and 50%,
      respectively). In the first group, 4 patients (11.1%) had urethral catheter
      obstruction: one was relieved by catheter flushing using sterile normal saline
      and three by suprapubic diversion. In the second group, urine retention was
      recorded in 2 patients (5.5%) and relieved by saline wash. CONCLUSION: The hole
      end catheter provides better bladder drainage with the ability to easily dislodge
      precipitations.

PMID- 11575523
TI  - Use of a urethral occlusion device for treatment of incontinence in a patient
      with heterotopic urinary diversion.
AB  - Incontinence is a frequent complication of continent cutaneous urinary diversion
      that usually requires surgical intervention for correction. We report a novel
      nonsurgical therapy for reservoir incontinence in a woman who underwent anterior
      pelvic exenteration with formation of an Indiana pouch urinary diversion for
      treatment of adenocarcinoma of the urethra. When she subsequently developed
      urinary incontinence that was only partially responsive to anticholinergic
      therapy, stomal continence was restored by using a disposable urethral occlusion
      device.

PMID- 11575524
TI  - Corporoscopic-assisted removal of ruptured inflatable penile prosthesis.
AB  - Despite the recent availability of effective oral agents for treatment of
      erectile dysfunction, many patients do not respond to oral therapy and do not
      desire injection therapy. For some of these patients, inflatable prostheses
      remain an effective form of treatment for erectile dysfunction; however,
      prostheses are not without their own set of complications. The most common
      complications are infection and mechanical failure. We present the case of
      mechanical failure of a prosthesis and the use of corporoscopy to assist in the
      removal and subsequent successful reimplantation of a new inflatable prosthesis.

PMID- 11575525
TI  - Pain and postoperative recovery.

PMID- 11575526
TI  - Postoperative visual loss: still no answers--yet.

PMID- 11575527
TI  - Acute pain induces insulin resistance in humans.
AB  - BACKGROUND: Painful trauma results in a disturbed metabolic state with impaired
      insulin sensitivity, which is related to the magnitude of the trauma. The authors
      explored whether pain per se influences hepatic and extrahepatic actions of
      insulin. METHODS: Ten healthy male volunteers underwent two randomly sequenced
      hyperinsulinemic-euglycemic (insulin infusion rate, 0.6 mU x kg(-1) x min(-1) for
      180 min) clamp studies 4 weeks apart. Self-controlled painful electrical
      stimulation was applied to the abdominal skin for 30 min, to a pain intensity of
      8 on a visual analog scale of 0-10, just before the clamp procedure (study P). In
      the other study, no pain was inflicted (study C). RESULTS: Pain reduced whole
      body insulin-stimulated glucose uptake from 6.37+/-1.87 mg x kg(-1) x min(-1)
      (mean +/- SD) in study C to 4.97+/-1.38 mg x kg(-1) x min(-1) in study P (P <
      0.01) because of a decrease in nonoxidative glucose disposal, as determined by
      indirect calorimetry (2.47+/-0.88 mg x kg(-1) x min(-1) in study P vs. 3.41+/
      1.03 mg x kg(-1) x min(-1) in study C; P < 0.05). Differences in glucose
      oxidation rates were not statistically significant. The suppression of
      isotopically determined endogenous glucose output during hyperinsulinemia tended
      to be decreased after pain (1.67+/-0.48 mg x kg(-1) x min(-1) in study P vs.
      2.04+/-0.45 mg x kg(-1) x min(-1) in study C; P = 0.06). Pain elicited a twofold
      to threefold increase in serum cortisol (P < 0.01), plasma epinephrine (P <
      0.05), and serum free fatty acids (P < 0.05). Similarly, circulating
      concentrations of glucagon and growth hormone tended to increase during pain.
      CONCLUSIONS: Acute severe pain decreases insulin sensitivity, primarily by
      affecting nonoxidative glucose metabolism. It is conceivable that the
      counterregulatory hormonal response plays an important role. This may indicate
      that pain relief in stress states is important for maintenance of normal glucose
      metabolism.

PMID- 11575528
TI  - Dose-dependent enhancement of in vivo GABA(A)-benzodiazepine receptor binding by
      isoflurane.
AB  - BACKGROUND: Abundant in vitro and animal model data suggest the postsynaptic
      gamma-aminobutyric acid receptor type A (GABA(A)-R) is an important target for
      volatile general anesthetics, but the relevance of these models is untested in
      humans. Because benzodiazepines have also been shown to act via a specific
      GABA(A)-R site, they provide sensitive probes for the GABA(A)-R. Availability of
      the 11C-labeled benzodiazepine ligand, flumazenil, allowed us to quantitatively
      test in humans whether the volatile anesthetic isoflurane affects GABA(A)-Rs in
      vivo in a dose-dependent manner. METHODS: 11C-flumazenil positron emission
      tomography scans were obtained in 12 healthy subjects while awake (control
      condition) and anesthetized with either 1.0 or 1.5 minimum alveolar concentration
      isoflurane (n = 7 and 5, respectively; isoflurane conditions). Regions of
      interest included areas of high, intermediate, and low GABA(A)-benzodiazepine
      site density. For each subject and experimental condition, the binding of 11C
      flumazenil, expressed as distribution volume (which linearly correlates to
      maximal binding site density and apparent ligand affinity), was obtained by curve
      fitting using a two-compartment model. RESULTS: The ratio of distribution volume
      increased significantly in each examined region during the isoflurane conditions
      compared with control conditions (P < 0.01, one-tailed t test). Furthermore, the
      increases in ratio of distribution volume during the 1.5-minimum alveolar
      concentration isoflurane condition were significantly greater than those measured
      during 1.0 minimum alveolar concentration isoflurane inhalation (P < 0.002, one
      tailed t test). CONCLUSIONS: Isoflurane exposure appeared to enhance receptor
      specific 11C-flumazenil binding in a dose-dependent manner. The results suggest
      the possibility that a conformational change of the GABA(A)-R is involved in the
      mechanism of action of isoflurane in the living human brain.

PMID- 11575529
TI  - North American malignant hyperthermia population: screening of the ryanodine
      receptor gene and identification of novel mutations.
AB  - BACKGROUND: Malignant hyperthermia (MH) is a disorder of skeletal muscle
      manifested as a life-threatening hypermetabolic crisis in susceptible individuals
      after exposure to inhalational anesthetics and depolarizing muscle relaxants.
      Mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1) are
      considered a common cause of the disorder, and, to date, more than 20 RYR1
      mutations have been reported in European and Canadian families. Some studies
      suggest that differences may exist in the frequencies and distribution of
      mutations in the RYR1 gene between European and North American MH families the
      frequency and distribution of mutations in the RYR1 gene. METHODS: Skeletal
      muscle samples from 73 unrelated individuals diagnosed as MH susceptible
      according to the North American MH caffeine-halothane contracture test were
      studied. Genomic DNA of MH-susceptible patients was investigated by polymerase
      chain reaction-based restriction fragment length polymorphism, single-strand
      conformation polymorphism, and sequencing analysis. The majority of known RYR1
      mutations were analyzed using the restriction fragment length polymorphism
      method, whereas new mutations were searched by single-strand conformation
      polymorphism in exons 12, 15, 39, 40, 44, 45, and 46 of the gene. RESULTS: Seven
      known RYR1 mutations (Arg163Cys, Gly248Arg, Arg614Cys, Val2168Met, Thr2206Met,
      Gly2434Arg, and Arg2454His) were detected at frequencies of 2.7, 1.4, 1.4, 1.4,
      1.4, 5.5, and 4.1%, respectively. In addition, three novel amino acid
      substitutions (Val2214Ile, Ala2367Thr, and Asp2431Asn) were detected at frequency
      of 1.4% each. These 10 mutations account for 21.9% of the North American MH
      susceptible population. CONCLUSION: Three novel candidate mutations in the RYR1
      gene were identified in these MH patients. The frequency and distribution of RYR1
      mutations observed in this North American MH population was markedly different
      from that previously identified in Europe. Larger-scale studies are necessary to
      clarify the type and frequency of mutations in RYR1 associated with MH in North
      American families.

PMID- 11575530
TI  - Response to mivacurium in a patient compound heterozygous for a novel and a known
      silent mutation in the butyrylcholinesterase gene: genotyping by sequencing.
AB  - BACKGROUND: Patients who are homozygous for the atypical mutation, compound
      heterozygous for atypical and silent mutations, or homozygous for silent
      mutations (SS) respond to mivacurium with extensively prolonged neuromuscular
      block. Although important, exact phenotyping of these patients is difficult. This
      article presents the pharmacodynamics and pharmacokinetics of a normal dose of
      mivacurium in a patient with phenotype SS, including a pedigree analysis and
      delineation of the molecular genetic method used to identify the genotype.
      METHODS: The neuromuscular block following administration of mivacurium, at a
      dose of 0.14 mg/kg, was monitored in a 30-yr-old healthy man with use of a
      mechanosensor and mechanomyography, and times to different levels of recovery
      were measured. Venous samples for determination of the mivacurium isomers were
      collected during the interval 134-494 min after administration of mivacurium, and
      the terminal half-lives were calculated. Butyrylcholinesterase activity,
      phenotype, and genotype were determined for both the patient and the family.
      Complete nucleotide sequencing was used to identify the genotype. RESULTS: A
      train-of-four ratio of 0.75 was reached 469 min after the injection of
      mivacurium. The terminal elimination half-lives of the mivacurium isomers, cis
      trans and trans-trans, were 90 min. Complete nucleotide sequencing revealed two
      point mutations, the known silent variant S7 and a previously undescribed
      mutation of amino acid residue 170 introducing a stop codon. CONCLUSIONS: The
      patient was compound heterozygous for silent mutations in the
      butyrylcholinesterase gene. The response to mivacurium was an extensively
      prolonged duration of action. Identification of the rare silent mutations
      presupposes access to modern molecular genetic methods such as complete
      nucleotide sequencing.

PMID- 11575531
TI  - Predictability of processed electroencephalography effects on the basis of
      pharmacokinetic-pharmacodynamic modeling during repeated propofol infusions in
      patients with extradural analgesia.
AB  - BACKGROUND: Pharmacokinetic-pharmacodynamic (PKPD) modeling can be used to
      characterize the concentration-effect relation of drugs. If the concentration
      effect relation of a hypnotic drug is stable over time, an effect parameter
      derived from the processed electroencephalographic signal may be used to control
      the infusion for hypnosis. Therefore, the stability of the propofol concentration
      electroencephalographic effect relation over time was investigated under non
      steady state conditions. METHODS: Three propofol infusions (25 mg x kg(-1) x h(
      1) for 10 min, 22 mg x kg(-1) x h(-1) for 10 min, and 12.5 mg x kg(-1) x h(-1)
      for 20 min) were administered to 10 patients during extradural analgesia. Each
      successive infusion was started immediately after the patient had regained
      responsiveness after termination of the preceding infusion.
      Electroencephalography was recorded from bilateral prefrontal to mastoid leads.
      Electroencephalographic amplitude in the 11- to 15-Hz band and the Bispectral
      Index were used as electroencephalographic effect variables. PKPD parameters were
      calculated with use of parametric and nonparametric models based on
      electroencephalographic data and arterial propofol concentrations derived during
      the initial infusion, and these were used to predict electroencephalographic
      effect during the subsequent infusions. The predictability of the
      electroencephalographic effects was determined by the coefficient of
      determination (R2) and of the -2 log likelihood of the sequential infusions.
      RESULTS: The direction of electroencephalographic changes in response to the
      infusions was reproducible. Although PKPD parameters could be estimated well
      during the initial infusion (median [range] parametric R2 = 0.74 [0.56-0.95] for
      electroencephalographic amplitude and 0.90 [0.27-0.99] for Bispectral Index),
      none of the modeling techniques could predict accurately the
      electroencephalographic effect during subsequent infusions (R2 = 0.00 [-0.31
      0.46] for electroencephalographic amplitude and 0.15 [-.46-0.57] for Bispectral
      Index; P < 0.01). CONCLUSIONS: The relation between blood propofol concentrations
      and the electroencephalographic effect under non-steady state conditions is not
      stable over time and is too complex to be modeled by any of the applied PKPD
      models.

PMID- 11575532
TI  - Randomized controlled trial of total intravenous anesthesia with propofol versus
      inhalation anesthesia with isoflurane-nitrous oxide: postoperative nausea with
      vomiting and economic analysis.
AB  - BACKGROUND: To assess the incidence of postoperative nausea and vomiting after
      total intravenous anesthesia (TIVA) with propofol versus inhalational anesthesia
      with isoflurane-nitrous oxide, the authors performed a randomized trial in 2,010
      unselected surgical patients in a Dutch academic institution. An economic
      evaluation was also performed. METHODS: Elective inpatients (1,447) and
      outpatients (563) were randomly assigned to inhalational anesthesia with
      isoflurane-nitrous oxide or TIVA with propofol-air. Cumulative incidence of
      postoperative nausea and vomiting was recorded for 72 h by blinded observers.
      Cost data of anesthetics, antiemetics, disposables, and equipment were collected.
      Cost differences caused by duration of postanesthesia care unit stay and
      hospitalization were analyzed. RESULTS: Total intravenous anesthesia reduced the
      absolute risk of postoperative nausea and vomiting up to 72 h by 15% among
      inpatients (from 61% to 46%, P < 0.001) and by 18% among outpatients (from 46% to
      28%, P < 0.001). This effect was most pronounced in the early postoperative
      period. The cost of anesthesia was more than three times greater for propofol
      TIVA. Median duration of stay in the postanesthesia care unit was 135 min after
      isoflurane versus 115 min after TIVA for inpatients (P < 0.001) and 160 min after
      isoflurane versus 150 min after TIVA for outpatients (P = 0.039). Duration of
      hospitalization was equal in both arms. CONCLUSION: Propofol TIVA results in a
      clinically relevant reduction of postoperative nausea and vomiting compared with
      isoflurane-nitrous oxide anesthesia (number needed to treat = 6). Both anesthetic
      techniques were otherwise similar. Anesthesia costs were more than three times
      greater for propofol TIVA, without economic gains from shorter stay in the
      postanesthesia care unit

PMID- 11575533
TI  - Ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in
      outpatient surgery.
AB  - BACKGROUND: A longer-acting local anesthetic agent, such as ropivacaine, may
      offer advantages over lidocaine for intravenous regional anesthesia. The
      objectives of this study were to evaluate whether the findings of volunteer
      investigations with intravenous regional anesthesia with ropivacaine (which have
      shown prolonged analgesia after release of the tourniquet) translates into
      improved pain control after surgery. METHODS: With Human Investigation Committee
      approval and a double-blind study design, 20 healthy patients with American
      Society of Anesthesiologists physical status I or II classification who were
      scheduled to undergo forearm and hand surgery were randomly assigned to
      administration of 40 ml of either 0.2% ropivacaine or 0.5% lidocaine for
      intravenous regional anesthesia. Evidence of central nervous system side effects,
      such as lightheadedness, tinnitus, and metallic taste, as well as cardiac
      arrhythmias, were evaluated and treated (if necessary) after local anesthetic
      administration, before and during surgery, and after release of the tourniquet
      until discharge from the postanesthesia care unit. Regression of sensory
      anesthesia in the nerve distributions of the forearm and hand was recorded.
      Verbal numerical pain scores were monitored and quantified until the patients
      were discharged to home from the postanesthesia care unit. Patient pain scores,
      side effect profiles, time to first oral intake, and total amount of oral
      analgesics were recorded 24 h postoperatively. RESULTS: Intravenous regional
      anesthesia with 0.2% ropivacaine and 0.5% lidocaine provided equivalent levels of
      surgical anesthesia. After release of the tourniquet, the first evidence for
      return of sensation in the distribution of the five peripheral nerves occurred
      later in the ropivacaine group (median, 20 min; range, 15-40 min) than in the
      lidocaine group (median, 1 min; range, 1-25 min). Verbal numerical pain scores
      were significantly lower at the time of admission, whereas during the remainder
      of the postanesthesia care unit stay and later at home, the difference in verbal
      numerical pain scores between the two groups was no longer statistically
      significant. CONCLUSIONS: Ropivacaine 0.2% may be an alternative to 0.5%
      lidocaine for intravenous regional anesthesia in the outpatient surgical setting.
      Longer-lasting analgesia in the immediate postoperative period may be due to a
      more profound and prolonged tissue binding effect of ropivacaine.

PMID- 11575534
TI  - Effects of lithotomy position and external compression on lower leg muscle
      compartment pressure.
AB  - BACKGROUND: Case reports have suggested that externally applied pressure from
      antithrombosis devices may contribute to the development of compartment syndromes
      during extended surgery in the lithotomy position. The purpose of this study was
      to assess the effects of a pneumatic compression device on directly measured
      intracompartment pressure in the lower leg with the leg positioned in the
      lithotomy position. METHODS: In 25 conscious, healthy men and women, the authors
      measured pressure within the tibialis anterior muscle compartment with the leg
      supine and in the lithotomy position with and without intermittent compression.
      Three different devices were used to keep the leg in the lithotomy position,
      supporting the leg either behind the knee, under the calf, or at the ankle.
      RESULTS: The lithotomy position with support behind the calf or knee increased
      intracompartment pressure to 16.5+/-3.4 versus 10.7+/-5.8 mmHg supine (mean +/-
      SD; P < 0.05). The addition of intermittent compression decreased pressure to
      13.4+/-5.1 mmHg during lithotomy (P < 0.05) and to 9.1+/-7.0 mmHg in the supine
      position (P < 0.05). In contrast, the lithotomy position with support near the
      ankle decreased intracompartment pressure to 8.7+/-5.6 versus 13.3+/-5.1 mmHg
      supine (P < 0.05). The addition of intermittent compression decreased pressure to
      6.5+/-5.4 mmHg during lithotomy (P < 0.05) and to 10.3+/-4.7 mmHg in the supine
      position (P < 0.05). CONCLUSIONS: These results show that the lithotomy position
      is associated with changes in intracompartment pressure that are dependent on the
      method of leg support used. Furthermore, they indicate that intermittent external
      compression can reduce intracompartment pressure in the lower leg. Therefore,
      increases in intracompartment pressure during surgery in the lithotomy position
      with the calf or knee supported may be one of the factors that contribute to the
      development of compartment syndrome. Further, use of intermittent external
      compression may significantly reduce this pressure increase.

PMID- 11575535
TI  - Clinical experience of percutaneous femoral venous catheterization in critically
      ill preterm infants less than 1,000 grams.
AB  - BACKGROUND: Venous access is relatively difficult in preterm infants. Central
      venous catheterization is indicated for pressure monitoring, drug therapy, and
      nutrition supplementation, which are often critical in the anesthetic management
      of infants undergoing major surgery. METHODS: In 49 critically ill preterm
      infants weighing less than 1,000 g, the femoral vein was cannulated using a 22
      gauge Angiocath (25 mm; Beckton Dickinson, Sandy, UT). A 2.5-ml syringe was
      attached to the Angiocath, and the Angiocath was advanced with constant negative
      pressure over the syringe. When blood return was observed, the cannula was
      advanced. When free blood reflux was achieved, a J wire was inserted, followed by
      a 24-gauge central venous catheter. RESULTS: The overall catheterization success
      rate was 79.6% (39 of 49 attempts). The time required for successful
      catheterization was less than 10 min in 18 cases (46.2%), 10-20 min in 17 cases
      (43.6%), and 20-30 min in 4 cases (10.3%). In the successful group, 1 catheter
      tip was positioned in the vein of the liver (2.6%), 2 were in the common iliac
      vein (5.1%), 6 were in the right atrium (15.4%), and 30 were in the infracardiac
      inferior vena cava (76.9%). Complications included hematoma in six cases (12.2%),
      arterial puncture in five cases (10.2%), bleeding in two cases (4.1%), and
      transient bradycardia in two cases (4.1%). CONCLUSIONS: The results indicate that
      percutaneous femoral venous catheterization is a reliable and valuable technique
      for critically ill preterm infants weighing less than 1,000 g.

PMID- 11575536
TI  - Magnesium sulfate does not reduce postoperative analgesic requirements.
AB  - BACKGROUND: Because magnesium blocks the N-methyl-D-aspartate receptor and its
      associated ion channels, it can prevent central sensitization caused by
      peripheral nociceptive stimulation. However, transport of magnesium from blood to
      cerebrospinal fluid (CSF) across the blood-brain barrier is limited in normal
      humans. The current study was designed to evaluate whether perioperative
      intravenous magnesium sulfate infusion affects postoperative pain. METHODS: Sixty
      patients undergoing abdominal hysterectomy received 50 mg/kg intravenous
      magnesium sulfate as a bolus dose followed by a continuous infusion of 15 mg x
      kg(-1) x h(-1) for 6 h (magnesium group) or the same volume of isotonic saline
      (control group). At the end of surgery, serum and CSF magnesium concentration
      were measured in both groups. The cumulative postoperative analgesic consumption
      was measured to assess the analgesic effect using a patient-controlled epidural
      analgesia device. Pain intensities at rest and during forced expiration were
      evaluated at 6, 24, 48, and 72 h postoperatively. RESULTS: At the end of surgery,
      patients in the magnesium group had significantly greater postoperative serum
      magnesium concentrations compared with both preoperative and control group values
      (P < 0.001). Despite significantly higher serum magnesium concentrations in the
      magnesium group, there was no significant difference in magnesium concentration
      measured in postoperative CSF. Cumulative postoperative analgesic doses were
      similar in both groups. However, there was observed an inverse relation between
      cumulative postoperative analgesic consumption and the CSF magnesium
      concentration in both groups. Visual analog pain scores at rest and during forced
      expiration were similar and less than 4 in both groups. CONCLUSIONS:
      Perioperative intravenous administration of magnesium sulfate did not increase
      CSF magnesium concentration and had no effects on postoperative pain. However, an
      inverse relation between cumulative postoperative analgesic consumption and the
      CSF magnesium concentration was observed. These results suggest that
      perioperative intravenous magnesium infusion may not be useful for preventing
      postoperative pain.

PMID- 11575537
TI  - Hemodynamic and catecholamine responses to laryngoscopy and tracheal intubation
      in patients with complete spinal cord injuries.
AB  - BACKGROUND: Endotracheal intubation in patients undergoing general anesthesia
      often causes hypertension and tachycardia, which may be altered when the efferent
      sympathetic fiber to the cardiovascular system is interrupted. The aim of the
      current study was to investigate the effects of different levels of spinal cord
      injury on the cardiovascular responses to intubation. METHODS: Fifty-four
      patients with traumatic complete cord injuries requiring tracheal intubation were
      grouped into quadriplegics (above C7; n = 22), high paraplegics (T1-T4, n = 8),
      and low paraplegics (below T5, n = 24) according to the level of injury. Twenty
      patients without spinal injury served as controls. Arterial pressure, heart rate,
      and rhythm were recorded at intervals for up to 5 min after intubation. Plasma
      concentrations of catecholamines were also measured. RESULTS: The intubation
      increased the systolic blood pressure similarly in control, high-paraplegic, and
      low-paraplegic groups (P < 0.05), whereas it did not alter the blood pressure in
      the quadriplegic group. Heart rate was significantly increased in all groups;
      however, the magnitude was more pronounced in the high-paraplegic group (67%)
      than in the control (38%) and quadriplegic (33%) groups. Plasma concentrations of
      norepinephrine were significantly increased after intubation in all groups;
      however, values were lower in the quadriplegic group and higher in the low
      paraplegic group compared with those in the control group. Incidence of
      arrhythmias did not differ among groups. CONCLUSIONS: The cardiovascular and
      plasma catecholamine changes associated with endotracheal intubation may differ
      according to the affected level in patients with complete spinal cord injuries.

PMID- 11575539
TI  - Different patterns of mast cell activation by muscle relaxants in human skin.
AB  - BACKGROUND: Activation of mast cells and systemic release of histamine are major
      side effects of intravenously administered muscle relaxants. In the current
      study, dermal microdialysis was used for the investigation of mast cell
      activation by muscle relaxants. Dermal microdialysis enabled simultaneous
      assessment of mediator release, vascular reactions, and sensory effects induced
      by intradermal application of muscle relaxants without systemic side effects.
      METHODS: Succinylcholine, the isoquinolines cisatracurium, atracurium, and
      mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and
      rapacuronium were tested in human volunteers (n = 6 each). After intradermal
      insertion of microdialysis capillaries (0.4 mm diameter, cutoff 3,000 kd) and a
      60-min equilibration period, the muscle relaxants were delivered via the
      capillaries for 30 min, followed by a 30-min washout period. Dialysate was
      sampled at 15-min intervals, and histamine, mast cell tryptase, and protein
      extravasation were determined. Changes in skin blood flow were measured using a
      laser Doppler imager. Potency and efficacy were derived from nonlinear fittings
      of the dose-response curves. RESULTS: For succinylcholine and the isoquinolines,
      dose-response curves for the vascular and sensory effects paralleled the
      histamine and tryptase release. In contrast, aminosteroids evoked a rapid
      histamine release that was accompanied by a delayed increase in tryptase.
      CONCLUSIONS: Dermal microdialysis has been successfully used to simultaneously
      assess mediator release, vascular reactions, and sensory effects. The different
      pattern of tryptase release by isoquinolines and aminosteroids suggests different
      mechanisms of mast cell activation.

PMID- 11575538
TI  - Use of intraoperative transesophageal echocardiography to predict atrial
      fibrillation after coronary artery bypass grafting.
AB  - BACKGROUND: Postoperative atrial fibrillation in coronary artery bypass graft
      surgery occurs in 10-40% of patients. It is associated with a significant degree
      of morbidity and results in prolonged lengths of stay in both the intensive care
      unit and hospital. METHODS: The authors prospectively evaluated patients
      undergoing coronary artery bypass with detailed transesophageal echocardiography
      examinations conducted before and after cardiopulmonary bypass to study whether
      risk factors for atrial fibrillation could be identified. Demographic and
      surgical parameters were also included in the analysis. Selected variables were
      subjected to univariate and subsequent multivariate analyses to test for their
      independent or joint influence on atrial fibrillation. RESULTS: Seventy-nine
      patients had assessable transesophageal echocardiography examinations.
      Significant univariate predictors of atrial fibrillation included advanced age (P
      = 0.002), pre-cardiopulmonary bypass left atrial appendage area (P = 0.04), and
      post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity
      ratio (P = 0.03). When these three factors were considered together in a multiple
      logistic regression analysis, left upper pulmonary vein systole/diastole velocity
      ratio was a significant predictor (P < 0.05), as was the joint effect of age plus
      pre-cardiopulmonary bypass left atrial appendage area (P = 0.005). The
      probability of developing atrial fibrillation for the combination of age = 75 yr,
      post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity
      ratio = 0.5, and left atrial appendage area = 4.0 cm was 0.83 (95% confidence
      interval, 0.51-0.96). CONCLUSIONS: Early identification of patients at risk for
      postoperative atrial fibrillation may be feasible using the parameters identified
      in this study.

PMID- 11575540
TI  - Phenylephrine added to prophylactic ephedrine infusion during spinal anesthesia
      for elective cesarean section.
AB  - BACKGROUND: Because ephedrine infusion (2 mg/min) does not adequately prevent
      spinal hypotension during cesarean delivery, the authors investigated whether
      adding phenylephrine would improve its efficacy. METHODS: Thirty-nine parturients
      with American Society of Anesthesiologists physical status I-II who were
      scheduled for cesarean delivery received a crystalloid preload of 15 ml/kg.
      Spinal anesthesia was performed using 11 mg hyperbaric bupivacaine, 2.5 microg
      sufentanil, and 0.1 mg morphine. Maternal heart rate and systolic blood pressure
      were measured at frequent intervals. A vasopressor infusion was started
      immediately after spinal injection of either 2 mg/min ephedrine plus 10
      microg/min phenylephrine or 2 mg/min ephedrine alone. Treatments were assigned
      randomly in a double-blind fashion. The infusion rate was adjusted according to
      systolic blood pressure using a predefined algorithm. Hypotension, defined as
      systolic blood pressure less than 100 mmHg and less than 80% of baseline, was
      treated with 6 mg ephedrine bolus doses. RESULTS: Hypotension occurred less
      frequently in the ephedrine-phenylephrine group than in the ephedrine-alone
      group: 37% versus 75% (P = 0.02). Ephedrine (36+/-16 mg, mean +/- SD) plus 178+/
      81 microg phenylephrine was infused in former group, whereas 54+/-18 mg ephedrine
      was infused in the latter. Median supplemental ephedrine requirements and nausea
      scores (0-3) were less in the ephedrine-phenylephrine group (0 vs. 12 mg, P =
      0.02; and 0 vs. 1.5, P = 0.01, respectively). Umbilical artery pH values were
      significantly higher in the ephedrine-phenylephrine group than in the group that
      received ephedrine alone (7.24 vs. 7.19). Apgar scores were similarly good in
      both groups. CONCLUSION: Phenylephrine added to an infusion of ephedrine halved
      the incidence of hypotension and increased umbilical cord pH.

PMID- 11575541
TI  - Low-concentration lidocaine rapidly inhibits axonal transport in cultured mouse
      dorsal root ganglion neurons.
AB  - BACKGROUND: Axonal transport plays a critical role in supplying materials for a
      variety of neuronal functions such as morphogenetic plasticity, synaptic
      transmission, and cell survival. In the current study, the authors investigated
      the effects of the analgesic agent lidocaine on axonal transport in neurites of
      cultured mouse dorsal root ganglion neurons. In relation to their effects, the
      effects of lidocaine on the growth rate of the neurite were also examined.
      METHODS: Isolated mouse dorsal root ganglion cells were cultured for 48 h until
      full growth of neurites. Video-enhanced microscopy was used to observe particles
      transported within neurites and to measure the neurite growth during control
      conditions and in the presence of lidocaine. RESULTS: Application of 30 microM
      lidocaine immediately reduced the number of particles transported in anterograde
      and retrograde axonal directions. These effects were persistently observed during
      the application (26 min) and were reversed by lidocaine washout. The inhibitory
      effect was dose-dependent at concentrations from 0.1 to 1,000 microM (IC50 = 10
      microM). In Ca2+-free extracellular medium, lidocaine failed to inhibit axonal
      transport. Calcium ionophore A23187 (0.1 microM) reduced axonal transport in both
      directions. The inhibitory effects of lidocaine and A23187 were abrogated by 10
      microM KN-62, a Ca2+-calmodulin-dependent protein kinase II inhibitor.
      Application of such low-concentration lidocaine (30 microM) for 30 min reduced
      the growth rate of neurites, and this effect was also blocked by KN-62.
      CONCLUSIONS: Low-concentration lidocaine rapidly inhibits axonal transport and
      neurite growth via activation of calmodulin-dependent protein kinase II.

PMID- 11575542
TI  - Propofol attenuates capacitative calcium entry in pulmonary artery smooth muscle
      cells.
AB  - BACKGROUND: Depletion of intracellular Ca2+ stores results in capacitative Ca2+
      entry (CCE) in pulmonary artery smooth muscle cells (PASMCs). The authors aimed
      to investigate the effects of propofol on CCE and to assess the extent to which
      protein kinase C (PKC) and tyrosine kinases mediate propofol-induced changes in
      CCE. METHODS: Pulmonary artery smooth muscle cells were cultured from explants of
      canine intrapulmonary artery. Fura 2-loaded PASMCs were placed in a dish (37
      degrees C) on an inverted fluorescence microscope. Intracellular Ca2+
      concentration was measured using fura 2 in PASMCs using a dual-wavelength
      spectrofluorometer. Thapsigargin (1 microM), a sarcoplasmic reticulum Ca2+
      adenosine triphosphatase inhibitor, was used to deplete intracellular Ca2+ stores
      after removing extracellular Ca2+. CCE was activated when extracellular Ca2+ (2.2
      mM) was restored. RESULTS: Thapsigargin caused a transient increase in
      intracellular Ca2+ concentration (182+/-11%). Restoring extracellular calcium (to
      induce CCE) resulted in a peak (246+/-12% of baseline) and a sustained (187+/-7%
      of baseline) increase in intracellular Ca2+ concentration. Propofol (1, 10, 100
      microM) attenuated CCE in a dose-dependent manner (peak: 85+/-3, 70+/-4, 62+/-4%;
      sustained: 94+/-5, 80+/-5, 72+/-5% of control respectively). Tyrosine kinase
      inhibition (tyrphostin 23) attenuated CCE (peak: 67+/-4%; sustained: 74+/-5% of
      control), but the propofol-induced decrease in CCE was still apparent after
      tyrosine kinases inhibition. PKC activation (phorbol 12-myristate 13-acetate)
      attenuated CCE (peak: 48+/-1%; sustained: 53+/-3% of control), whereas PKC
      inhibition (bisindolylmaleimide) potentiated CCE (peak: 132+/-11%; sustained:
      120+/-4% of control). Moreover, PKC inhibition abolished the propofol-induced
      attenuation of CCE. CONCLUSION: Tyrosine kinases activate and PKC inhibits CCE in
      PASMCs. Propofol attenuates CCE primarily via a PKC-dependent pathway. CCE should
      be considered a possible cellular target for anesthetic agents that alter
      vascular smooth muscle tone.

PMID- 11575543
TI  - Desflurane, sevoflurane, and isoflurane affect left atrial active and passive
      mechanical properties and impair left atrial-left ventricular coupling in vivo:
      analysis using pressure-volume relations.
AB  - BACKGROUND: The effects of volatile anesthetics on left atrial function in vivo
      have not been described. The authors tested the hypothesis that desflurane,
      sevoflurane, and isoflurane alter left atrial mechanics evaluated with invasively
      derived pressure-volume relations. METHODS: Barbiturate-anesthetized dogs (n =
      24) were instrumented for measurement of aortic, left atrial, and left
      ventricular pressures (micromanometers) and left atrial volume (orthogonal
      sonomicrometers). Left atrial contractility and chamber stiffness were assessed
      with end-systolic and end-reservoir pressure-volume relations, respectively,
      obtained from differentially loaded diagrams. Relaxation was determined from the
      slope of left atrial pressure decline after contraction. Stroke work and
      reservoir function were assessed by A and V loop areas, respectively. Left atrial
      left ventricular coupling was determined by the ratio of left atrial
      contractility and left ventricular elastance. Dogs received 0.6, 0.9, and 1.2
      minimum alveolar concentration desflurane, sevoflurane, or isoflurane in a random
      manner, and left atrial function was determined after 20-min equilibration at
      each dose. RESULTS: Desflurane, sevoflurane, and isoflurane decreased heart rate,
      mean arterial pressure, and maximal rate of increase of left ventricular pressure
      and increased left atrial end-diastolic, end-systolic, and maximum volumes. All
      three anesthetics caused dose-related reductions in left atrial contractility,
      relaxation, chamber stiffness, and stroke work. Administration of 0.6 and 0.9
      minimum alveolar concentration desflurane, sevoflurane, and isoflurane increased
      V loop area. All three anesthetics decreased the ratio of stroke work to total
      left atrial pressure-volume diagram area, increased the ratio of conduit to
      reservoir volume, and reduced left atrial contractility-left ventricular
      elastance to equivalent degrees. CONCLUSIONS: The results indicate that
      desflurane, sevoflurane, and isoflurane depress left atrial contractility, delay
      relaxation, reduce chamber stiffness, preserve reservoir and conduit function,
      and impair left atrial-left ventricular coupling in vivo.

PMID- 11575544
TI  - Myocardial and coronary effects of propofol in rabbits with compensated cardiac
      hypertrophy.
AB  - BACKGROUND: Myocardial effects of propofol have been previously investigated but
      most studies have been performed in healthy hearts. This study compared the
      cardiac effects of propofol on isolated normal and hypertrophic rabbits hearts.
      METHODS: The effects of propofol (10-1,000 microM) on myocardial contractility,
      relaxation, coronary flow and oxygen consumption were investigated in hearts from
      rabbits with pressure overload-induced left ventricular hypertrophy (LVH group, n
      = 20) after aortic abdominal banding and from sham-operated control rabbits (SHAM
      group, n = 10), using an isolated and erythrocyte-perfused heart model. In
      addition, to assess the myocardial and coronary effects of propofol in more
      severe LVH, hearts with a degree of hypertrophy greater than 140% were selected
      (severe LVH group, n = 7). RESULTS: The cardiac hypertrophy model induced
      significant left ventricular hypertrophy (136+/-21%, P < 0.05). The pressure
      volume relation showed normal systolic function but an altered diastolic
      compliance in hypertrophic hearts. Propofol only decreased myocardial
      contractility and relaxation at supratherapeutic concentrations (> or = 300
      microM) in SHAM and LVH groups. The decrease in myocardial performances was not
      significantly different in SHAM and LVH groups. Propofol induced a significant
      increase in coronary blood flow which was not significantly different between
      groups. In severe LVH group, the degree of hypertrophy reached to 157+/-23%.
      Similarly, the effects of concentrations of propofol were not significantly
      different from the SHAM group. CONCLUSIONS: Propofol only decreased myocardial
      function at supratherapeutic concentrations. The myocardial and coronary effects
      of propofol were not significantly modified in cardiac hypertrophy.

PMID- 11575545
TI  - Lesions of the basolateral amygdala complex block propofol-induced amnesia for
      inhibitory avoidance learning in rats.
AB  - BACKGROUND: As the unitary theory of anesthesia gives way to the "multiple sites,
      multiple mechanisms" concept, the sites involved in mediating the components of
      anesthesia must be identified. In the current study, we test the hypothesis that
      the basolateral amygdala complex (BLAC) is a brain site involved with mediating
      propofol-induced amnesia. METHODS: Male Sprague-Dawley rats were divided into two
      groups, sham-operated control animals and rats given bilateral excitotoxic N
      methyl-D-aspartate lesions of the BLAC. For each group, animals were given
      intraperitoneal saline or propofol (25 mg/kg) 5 min before inhibitory avoidance
      learning. Rats were given a foot shock (0.4 mA) upon entering the dark side of a
      two-sided apparatus. Rats could escape additional shock by returning to and
      staying in the light side. Training ended after shock avoidance for greater than
      60 s. Memory was tested at 24 h. Longer latencies to enter the dark side 24 h
      after training imply better memory. RESULTS: Sham-saline-treated animals had a
      robust memory latency (median latency [interquartile range] = 300 [163-567] s).
      Sham-propofo-treated animals exhibited a significant anterograde amnesia (latency
      = 63 [14-111] s) (P < 0.05 vs. sham-saline-treated animal). Both the saline
      injected and propofol-injected animals with BLAC lesions showed robust memory
      (latency = 300 [264-485] and 323 [143480] s, respectively). These latencies did
      not differ from performance in the sham-saline-treated group and were
      significantly higher than the latency of the sham-propofol-treated group (both P
      < 0.05). CONCLUSIONS: Discrete BLAC lesions blocked the amnestic effect of
      propofol. BLAC activity appears to be a requirement for propofol-induced amnesia.
      This finding suggests that the BLAC is a key brain site mediating anesthetic
      induced amnesia.

PMID- 11575546
TI  - Autosomal dominant canine malignant hyperthermia is caused by a mutation in the
      gene encoding the skeletal muscle calcium release channel (RYR1).
AB  - BACKGROUND: Malignant hyperthermia (MH) is an inherited disorder of skeletal
      muscle characterized by hypercarbia, rhabdomyolysis, generalized skeletal muscle
      contracture, cardiac dysrhythmia, and renal failure, that develops on exposure to
      succinylcholine or volatile anesthetic agents. All swine and up to 50% of human
      MH events are thought to be associated with mutations in the calcium release
      channel of the sarcoplasmic reticulum, also known as the ryanodine receptor
      (RYR1). Events resembling MH have been reported in other species, but none have
      undergone genetic investigation to date. METHODS: To determine the molecular
      basis of canine MH, a breeding colony was established with a male, mixed-breed,
      MH-susceptible (MHS) dog that survived an in vivo halothane-succinylcholine
      challenge. He was mated to three unaffected females to produce four litters and
      back-crossed to an affected daughter to produce one litter. One of his MHS sons
      was mated to an unaffected female to produce an additional litter. Forty-seven
      dogs were phenotyped with an in vitro contracture test and diagnosed as MHS or MH
      normal based on the North American in vitro contracture test protocol. Nine
      microsatellite markers in the vicinity of RYR1 on canine chromosome 1 (CFA01)
      were tested for linkage to the MHS phenotype. Mutational analysis in two MHS and
      two MH-normal dogs was performed with direct sequencing of polymerase chain
      reaction products and of cloned fragments that represent frequently mutated human
      RYR1 regions. A restriction fragment length polymorphism was chosen to detect the
      candidate mutation in the pedigree at large. RESULTS: Pedigree inspection
      revealed that MHS in this colony is transmitted as an autosomal dominant trait.
      FH2294, the marker closest to RYR1, is linked to MHS at a theta = 0.03 with a LOD
      score of 9.24. A T1640C mutation gives rise to an alanine for valine substitution
      of amino acid 547 in the RYR1 protein, generating a maximum LOD score of 12.29 at
      theta = 0.00. All dogs diagnosed as MHS by in vitro contracture test were
      heterozygous for the mutation, and all MH-normal dogs were homozygous for the
      T1640 allele. CONCLUSIONS: These results indicate that autosomal dominant canine
      MH is caused by a mutation in the gene encoding the skeletal muscle calcium
      release channel and that the MHS trait in this pedigree of mixed-breed dogs is in
      perfect cosegregation with the RYR1 V547A mutation.

PMID- 11575547
TI  - Direct neurotoxicity of tetracaine on growth cones and neurites of growing
      neurons in vitro.
AB  - BACKGROUND: Local anesthetics have direct neurotoxicity on neurons. However,
      precise morphologic changes induced by the direct application of local
      anesthetics to neurons have not yet been fully understood. Also, despite the fact
      that local anesthetics are sometimes applied to the sites where peripheral nerves
      may be regenerating after injury, the effects of local anesthetics on growing or
      regenerating neurons have never been studied. METHODS: Three different neuronal
      tissues (dorsal root ganglion, retinal ganglion cell layer, and sympathetic
      ganglion chain) were isolated from an age-matched chick embryo and cultured for
      20 h. Effects of tetracaine were examined microscopically and by a quantitative
      morphologic assay, growth cone collapse assay. RESULTS: Tetracaine induced growth
      cone collapse and neurite destruction. Three neuronal tissues showed
      significantly different dose-response, both at 60 min and at 24 h after the
      application of tetracaine (P < 0.01). The ED50 values (mean +/- SD) at 60 min
      were 1.53+/-1.05 mM in dorsal root ganglion, 0.15+/-0.05 mM in retinal, and
      0.06+/-0.02 mM in sympathetic ganglion chain cultures. The ED50 values at 24 h
      were 0.43+/-0.15 mM in dorsal root ganglion, 0.07+/-0.03 mM in retinal, and
      0.02+/-0.01 mM in sympathetic ganglion chain cultures. Concentration of nerve
      growth factor in the culture media did not influence the ED50 values. The growth
      cone collapsing effect was partially reversible in dorsal root ganglion and
      retinal neurons. However, in the sympathetic ganglion culture, no reversibility
      was observed after exposure to 1 mM tetracaine for 10 or for 60 min. Bupivacaine
      had similar neurotoxicity to the three types of growing neurons. (The ED50 values
      at 60 min were 2.32+/-0.50 mM in dorsal root ganglion, 0.96+/-0.16 mM in retinal,
      and 0.18+/-0.05 mM in sympathetic ganglion chain cultures. The ED50 values at 24
      h were 0.34+/-0.09 mM in dorsal root ganglion, 0.21+/-0.06 mM in retinal, and
      0.45+/-0.10 mM in sympathetic ganglion chain cultures.) CONCLUSIONS: Short-term
      exposure to tetracaine produced irreversible changes in growing neurons. Growth
      cones were quickly affected, and neurites degenerated subsequently. Sensitivity
      varied with neuronal type and was not influenced by the concentration of nerve
      growth factor. Because a similar phenomenon was observed after exposure to
      bupivacaine, the toxicity to growing neurons may not be unique to tetracaine.

PMID- 11575548
TI  - Minimum alveolar concentration of volatile anesthetics in rats during postnatal
      maturation.
AB  - BACKGROUND: Although neonatal rats have become widely used as experimental
      laboratory animals, minimum alveolar concentration (MAC) values of volatile
      anesthetics in rats during postnatal maturation remain unknown. METHODS: We
      determined MAC values of volatile anesthetics in spontaneously breathing neonatal
      (2-, 9-, and 30-day-old) and adult Wistar rats exposed to increasing (in 0.1-0.2%
      steps) concentrations of halothane, isoflurane, or sevoflurane (n = 12-20 in each
      group), using the tail-clamp technique. MAC and its 95% confidence intervals were
      calculated using logistic regression and corrected for body temperature (37
      degrees C). RESULTS: In adult rats, inspired MAC values corrected at 37 degrees C
      were as follows: halothane, 0.88% (confidence interval, 0.82-0.93%); isoflurane,
      1.12% (1.07-1.18%); and sevoflurane, 1.97% (1.84-2.10%). In 30-day-old rats, the
      values were as follows: halothane, 1.14% (1.07-1.20%); isoflurane, 1.67% (1.58
      1.76%); and sevoflurane, 2.95% (2.75-3.15%). In 9-day-old rats, inspired MAC
      values were as follows: halothane, 1.68% (1.58-1.78%); isoflurane, 2.34% (2.21
      2.47%); and sevoflurane, 3.74% (3.64-3.86%). In 2-day-old rats, inspired MAC
      values were as follows: halothane, 1.54% (1.44-1.64%); isoflurane, 1.86% (1.72
      2.01%); and sevoflurane, 3.28% (3.09-3.47%). CONCLUSION: As postnatal age
      increases, MAC value significantly increases, reaching the greatest value in 9
      day-old rats, and decreases thereafter, and at 30 days is still greater than the
      adult MAC value.

PMID- 11575549
TI  - Opioid action on respiratory neuron activity of the isolated respiratory network
      in newborn rats.
AB  - BACKGROUND: Underlying mechanisms behind opioid-induced respiratory depression
      are not fully understood. The authors investigated changes in burst rate,
      intraburst firing frequency, membrane properties, as well as presynaptic and
      postsynaptic events of respiratory neurons in the isolated brainstem after
      administration of opioid receptor agonists. METHODS: Newborn rat brainstem-spinal
      cord preparations were used and superfused with mu-, kappa-, and delta-opioid
      receptor agonists. Whole cell recordings were performed from three major classes
      of respiratory neurons (inspiratory, preinspiratory, and expiratory). RESULTS: Mu
      and kappa-opioid receptor agonists reduced the spontaneous burst activity of
      inspiratory neurons and the C4 nerve activity. Forty-two percent of the
      inspiratory neurons were hyperpolarized and decreased in membrane resistance
      during opioid-induced respiratory depression. Furthermore, under synaptic block
      by tetrodotoxin perfusion, similar changes of inspiratory neuronal membrane
      properties occurred after application of mu- and kappa-opioid receptor agonists.
      In contrast, resting membrane potential and membrane resistance of preinspiratory
      and majority of expiratory neurons were unchanged by opioid receptor agonists,
      even during tetrodotoxin perfusion. Simultaneous recordings of inspiratory and
      preinspiratory neuronal activities confirmed the selective inhibition of
      inspiratory neurons caused by mu- and kappa-opioid receptor agonists. Application
      of opioids reduced the slope of rising of excitatory postsynaptic potentials
      evoked by contralateral medulla stimulation, resulting in a prolongation of the
      latency of successive first action potential responses. CONCLUSIONS: Mu- and
      kappa-opioid receptor agonists caused reduction of final motor outputs by mainly
      inhibiting medullary inspiratory neuron network. This inhibition of inspiratory
      neurons seems to be a result of both a presynaptic and postsynaptic inhibition.
      The central respiratory rhythm as reflected by the preinspiratory neuron burst
      rate was essentially unaltered by the agonists.

PMID- 11575550
TI  - Only carbon dioxide absorbents free of both NaOH and KOH do not generate compound
      A during in vitro closed-system sevoflurane: evaluation of five absorbents.
AB  - BACKGROUND: Insufficient data exist on the production of compound A during closed
      system sevoflurane administration with newer carbon dioxide absorbents. METHODS:
      A modified PhysioFlex apparatus (Drager, Lubeck, Germany) was connected to an
      artificial test lung (inflow at the top of the bellow approximately/= 160 ml/min
      CO2; outflow at the Y piece of the lung model approximately/= 200 ml/min,
      simulating oxygen consumption). Ventilation was set to obtain an end-tidal carbon
      dioxide partial pressure of approximately 40 mmHg. Various fresh carbon dioxide
      absorbents were used: Sodasorb (n = 6), Sofnolime (n = 6), and potassium
      hydroxide (KOH)-free Sodasorb (n = 7), Amsorb (n = 7), and lithium hydroxide (n =
      7). After baseline analysis, liquid sevoflurane was injected into the circuit by
      syringe pump to obtain 2.1% end-tidal concentration for 240 min. At baseline and
      at regular intervals thereafter, end-tidal carbon dioxide partial pressure, end
      tidal sevoflurane concentration, and canister inflow (T degrees(in)) and canister
      outflow (T degrees(out)) temperatures were measured. To measure compound Ainsp
      concentration in the inspired gas of the breathing circuit, 2-ml gas samples were
      taken and analyzed by capillary gas chromatography plus mass spectrometry.
      RESULTS: The median (minimum-maximum) highest compound Ainsp concentrations over
      the entire period were, in decreasing order: 38.3 (28.4-44.2)* (Sofnolime), 30.1
      (23.9-43.7) (KOH-free Sodasorb), 23.3 (20.0-29.2) (Sodasorb), 1.6 (1.3-2.1)*
      (lithium hydroxide), and 1.3 (1.1-1.8)* (Amsorb) parts per million (*P < 0.01 vs.
      Sodasorb). After reaching their peak concentration, a decrease for Sofnolime, KOH
      free Sodasorb, and Sodasorb until 240 min was found. The median (minimum-maximum)
      highest values for T degrees(out) were 39 (38-40), 40 (39-42), 41 (40-42), 46 (44
      48)*, and 39 (38-41) degrees C (*P < 0.01 vs. Sodasorb), respectively.
      CONCLUSIONS: With KOH-free (but sodium hydroxide [NaOH]-containing) soda limes
      even higher compound A concentrations are recorded than with standard Sodasorb.
      Only by eliminating KOH as well as NaOH from the absorbent (Amsorb and lithium
      hydroxide) is no compound A produced.

PMID- 11575551
TI  - Effects of volatile anesthetics on N-methyl-D-aspartate excitotoxicity in primary
      rat neuronal-glial cultures.
AB  - BACKGROUND: Volatile anesthetics are known to ameliorate experimental ischemic
      brain injury. A possible mechanism is inhibition of excitotoxic cascades induced
      by excessive glutamatergic stimulation. This study examined interactions between
      volatile anesthetics and excitotoxic stress. METHODS: Primary cortical neuronal
      glial cultures were exposed to N-methyl-D-aspartate (NMDA) or glutamate and
      isoflurane (0.1-3.3 mM), sevoflurane (0.1-2.9 mM), halothane (0.1-2.9 mM), or 10
      microM (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen
      maleate (MK-801). Lactate dehydrogenase release was measured 24 h later. In other
      cultures, effects of volatile anesthetics on Ca++ uptake and mitochondrial
      membrane potential were determined in the presence or absence of NMDA (0-200
      microM). RESULTS: Volatile anesthetics reduced excitotoxin induced lactate
      dehydrogenase release by up to 52% in a dose-dependent manner. At higher
      concentrations, this protection was reversed. When corrected for olive oil
      solubility, the three anesthetics offered equivalent protection. MK-801 provided
      near-complete protection. Ca++ uptake was proportionally reduced with increasing
      concentrations of anesthetic but did not account for reversal of protection at
      higher anesthetic concentrations. Given equivalent NMDA-induced Ca++ loads, cells
      treated with volatile anesthetic had greater lactate dehydrogenase release than
      those left untreated. At protective concentrations, volatile anesthetics
      partially inhibited NMDA-induced mitochondrial membrane depolarization. At higher
      concentrations, volatile anesthetics alone were sufficient to induce
      mitochondrial depolarization. CONCLUSIONS: Volatile anesthetics offer similar
      protection against excitotoxicity, but this protection is substantially less than
      that provided by selective NMDA receptor antagonism. Peak effects of NMDA
      receptor antagonism were observed at volatile anesthetic concentrations
      substantially greater than those used clinically.

PMID- 11575552
TI  - Lidocaine and mexiletine inhibit mitochondrial oxidation in rat ventricular
      myocytes.
AB  - BACKGROUND: Accumulating evidence suggests that mitochondrial rather than
      sarcolemmal adenosine triphosphate-sensitive K+ (K(ATP)) channels may have an
      important role in the protection of myocardium during ischemia. Because both
      lidocaine and mexiletine are frequently used antiarrhythmic drugs during
      myocardial ischemia, it is important to investigate whether they affect
      mitochondrial K(ATP) channel activities. METHODS: Male Wistar rats were
      anesthetized with ether. Single, quiescent ventricular myocytes were dispersed
      enzymatically. The authors measured flavoprotein fluorescence to evaluate
      mitochondrial redox state. Lidocaine or mexiletine was applied after
      administration of diazoxide (25 microM), a selective mitochondrial K(ATP) channel
      opener. The redox signal was normalized to the baseline flavoprotein fluorescence
      obtained during exposure to 2,4-dinitrophenol, a protonophore that uncouples
      respiration from ATP synthesis and collapses the mitochondrial potential.
      RESULTS: Diazoxide-induced oxidation of flavoproteins and the redox changes were
      inhibited by 5-hydroxydecanoic acid, a selective mitochondrial K(ATP) channel
      blocker, suggesting that flavoprotein fluorescence can be used as an index of
      mitochondrial oxidation mediated by mitochondrial K(ATP) channels. Lidocaine (10(
      3) to 10 mM) and mexiletine (10(-3) to 10 mM) reduced oxidation of the
      mitochondrial matrix in a dose-dependent manner with an EC50 of 98+/-63 microM
      for lidocaine and 107+/-89 microM for mexiletine. CONCLUSIONS: Both lidocaine and
      mexiletine reduced flavoprotein fluorescence induced by diazoxide in rat
      ventricular myocytes, indicating that these antiarrhythmic drugs may produce
      impairment of mitochondrial oxidation mediated by mitochondrial K(ATP) channels.

PMID- 11575553
TI  - Thoracic paravertebral block.

PMID- 11575554
TI  - The anesthesiologist in critical care medicine: past, present, and future.

PMID- 11575555
TI  - From control of airway and breathing to cardiopulmonary-cerebral resuscitation.
      1958.

PMID- 11575556
TI  - Unilateral blindness after prone lumbar spine surgery.

PMID- 11575557
TI  - Off-pump coronary artery bypass surgery in a patient with C1 esterase inhibitor
      deficiency.

PMID- 11575558
TI  - Successful use of combined high-frequency oscillatory ventilation, inhaled nitric
      oxide, and prone positioning in the acute respiratory distress syndrome.

PMID- 11575559
TI  - Anesthetic management for patients with postpolio syndrome receiving
      electroconvulsive therapy.

PMID- 11575560
TI  - Prolonged Horner syndrome due to neck hematoma after continuous interscalene
      block.

PMID- 11575561
TI  - Comparison between sevoflurane and propofol neuromuscular effects in a patient
      with myasthenia gravis: effective doses of vecuronium.

PMID- 11575562
TI  - In vitro effects of fluoride on pseudocholinesterase activity and the metabolism
      of the cis-trans and trans-trans isomers of mivacurium.

PMID- 11575563
TI  - Methodological remarks on transcranial Doppler ultrasonography for PFO detection.

PMID- 11575564
TI  - Is chloride or dilution of bicarbonate the cause of metabolic acidosis from fluid
      administration?

PMID- 11575565
TI  - What is the clinical relevance of dilutional acidosis?

PMID- 11575566
TI  - Rhinorrhea by nasal fentanyl.

PMID- 11575567
TI  - Costs and recovery profiles of caudal anesthesia for anorectal surgery in adults.

PMID- 11575569
TI  - Using a spinal needle as an introducer for a spinal needle.

PMID- 11575568
TI  - Opening anesthesiologist-proof vials.

PMID- 11575570
TI  - A leak in a capnography sampling line induced a difference between arterial and
      end-tidal CO2.

PMID- 11575571
TI  - The release of dissolved gases from solution during decompression after
      hyperbaric treatment: effervescent tables and Henry's law.

PMID- 11575572
TI  - Folic acid-responsive neurological diseases in Japan.
AB  - Folic acid (folate) levels were measured in the serum of patients with various
      neurological diseases in Japan. Thirty-six patients showed decreased serum folate
      levels among 343 consecutive neurological patients (10.5%). Folate administration
      (15 mg/d) to folate-deficient patients improved neurological symptoms in 24 of 36
      cases (67%). Serum folate levels were significantly lower in female than in male
      folate-deficient patients. Folate-deficient patients showed predominantly axonal
      neuropathy, which responded to folate supplementation more markedly. Male
      patients more frequently exhibited neuropathy, especially demyelinating and motor
      dominant neuropathy, than females. Anemia was correlated with male sex and low
      serum folate levels. Male patients were more responsive than females to folate
      treatment. More male patients had taken excess alcohol or received gastrectomies
      than females. Neurological symptoms were more frequently improved by folate
      supplementation in patients with neuropathy than exclusive encephalopathy. Serum
      folate levels were lower in patients with encephalopathy, especially those with
      dementia, while folate therapy was more effective in neurological patients
      without dementia. Dysgeusia and anemia improved in all patients after folate
      administration. Neurological patients with malabsorption or treated with
      continuous drip infusion were resistant to folate therapy. Since folate
      responsive neuroencepahlopathies are not rare among patients with neurological
      diseases in Japan, the serum folate level would serve as a valuable indicator for
      folate supplement therapy.

PMID- 11575573
TI  - Effect of vitamin B6 deficiency on the synthesis and accumulation of S
      adenosylhomocysteine and S-adenosylmethionine in rat tissues.
AB  - The effect of vitamin B6-deficiency on the B6-vitamer concentrations, level of S
      adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) were studied in rat
      tissues. The plasma pyridoxal 5'-phosphate (PLP) and, pyridoxal (PL) levels were
      lower in the B6-deficient group compared to the control group. After 5 weeks of
      feeding the experimental diets, tissue PLP, pyridoxamine 5'-phosphate (PMP) and
      PL concentrations were significantly lower in the B6-deficient group compared to
      the control and the pair-fed control groups. Thymus PLP and PL levels were lower
      in the B6-deficient group. The concentration of SAM in the B6-deficient group
      decreased to approximately 50% and 25% in liver and thymus, respectively. However
      SAH concentration was 3.5 and 2 fold higher compared to the control and the pair
      fed control groups. Thus, the ratio of SAM/SAH was significantly decreased in the
      B6-deficient group compared to the control or the pair fed-control group. In
      addition, the S-adenosylhomocysteine hydrolase (EC 3.3.1.1) activity increased by
      45% and 15% in liver and thymus, respectively, in the B6-deficient group compared
      to the pair-fed control and the control groups. However, the activity of L
      methionine S-adenosyltransferase (EC 2.5.1.6) was also unaffected. Concentrations
      of SAH and SAM, SAM/SAH ratio and activities of S-adenosylhomocysteine hydrolase
      and L-methionine S-adenosyltrasferase in rat brain were not affected by the B6
      deficiency. We infer that the alteration of B6 metabolism, especially the
      reduction of PLP contents in liver and thymus, caused by the B6 deficiency,
      resulted in accumulation of SAH as well as reduction of SAM and the SAM/SAH
      ratio. The reduction of the SAM/SAH ratio was due to a block in the catabolism of
      methionine via the trans-sulfuration pathway. These may lead to inhibition of
      transmethylation reaction of DNA, RNA and protein, the synthesis and function of
      thymic lymphocyte and result in damage to tissues.

PMID- 11575574
TI  - Change in calcium balance and bone mineral density during pregnancy in female
      rats.
AB  - This study investigated changes in Ca balance and BMD during pregnancy in female
      rats. During pregnancy, the intestinal Ca absorption increased significantly, and
      Ca accumulation was also markedly elevated. However, BMD values for the lumbar
      spine decreased significantly during pregnancy. Twenty female SD rats, 10 weeks
      of age (Japan SLC Co., Shizuoka, Japan) were acclimated for 2 weeks. Then, the
      rats were divided into two groups; the control (no pregnancy) group (n=10) and
      the pregnant group (n=10). The rats in the pregnant group were kept in a cage
      with a male rat for 5 days at 12 weeks of age, and all 10 were successfully
      impregnated. During the pregnancy period, the values for intestinal Ca absorption
      and the rate of the intestinal Ca absorption in the pregnant group were
      significantly greater than those of the control group. In addition, in spite of
      the significant increase in urinary Ca excretion in the pregnant group, the Ca
      accumulation was markedly elevated during the latter half of pregnancy. On the
      other hand, the BMD value in the lumbar spine for the pregnant group
      significantly decreased during pregnancy. These findings suggest that pregnancy
      accelerated intestinal Ca absorption and Ca accumulation in female rats, while
      the lumbar spine BMD decreased during pregnancy.

PMID- 11575575
TI  - Subchronic toxicity of fish oil concentrates in male and female rats.
AB  - There are an overwhelming number of reports indicating the beneficial effects of
      fish oil supplements in human and animal nutrition. The purpose of this study,
      second in a series, was to evaluate the effects, particularly those that may be
      harmful, of high-dose, long-term consumption of fish oil concentrates (FOC) using
      male and female rats. One hundred and twenty male and 120 female rats were
      gavaged daily with oils and oil mixtures in a volume equal to 0.5% body weight (5
      mL/kg/d) for 13 weeks. The administered oils were corn oil, pure menhaden oil
      (MO), pure MaxEPA fish oil or different mixtures of corn oil with MO. The
      stability and the homogeneity of the dosing solutions were tested under study
      conditions. The animals received isocaloric and isonitrogenous diets throughout.
      Food and pure water were supplied ad libitum. At the end of the in-life phase of
      the study, the animals were anaesthetized with CO2 and humanely killed by
      exsanguination. Blood and other tissues were prepared for various clinical,
      histopathological and laboratory tests. Some beneficial effects of FOC, such as
      reduction in total serum cholesterol, in rats were confirmed. However, we also
      observed a significant reduction in absolute amount of serum HDL and a
      significant increase in relative liver and spleen weights in both sexes with the
      high dose of FOC. High doses of FOC (5 mL/kg/d) reduced serum iron and vitamin E
      concentrations. A reduction in osmotic fragility of RBC as well as an increase in
      RBC deformity were also observed in rats treated with high doses of FOC. These
      rats showed a significant overall increase in WBC count. We conclude that in
      rats, subchronic consumption of high levels of FOC can be beneficial but may also
      be harmful because of induction of clinical abnormalities including increased red
      cell deformity, increased relative liver and spleen weights, and reduced serum
      HDL, iron and vitamin E concentrations.

PMID- 11575577
TI  - A validation study on a method to estimate nutrient intake by family members
      through a household-based food-weighing survey.
AB  - The aim of the present study is to investigate the validity of a new method to
      estimate the food intake of individual subjects by a household-based dietary
      survey. The new method is based on the combination of household-based food
      weighing and approximating the proportions by which family members shared each
      dish or food in the household, which has been one of the components of the
      National Nutrition Survey, Japan, since 1995. We analyzed two sets of data from
      64 volunteers (female students taking a dietitian course and their mothers) in 32
      households by the approximated proportion method (method A) and the individual
      based food weighing method (B) as a reference measurement. Energy and
      macronutrient intake by individual subjects estimated by method A was highly
      correlated to the corresponding values by method B (Pearson's correlation
      coefficients: r=0.90-0.92). Average energy intake was likely to be underestimated
      by method A compared with method B, being lower by 94 kcal (6.2% of the reference
      value in method B), at least in the young and middle-aged female adults that were
      the subjects of this study. When intake of boiled rice was separately analyzed,
      underestimation of energy intake by method A was 44 kcal, which contributed to
      approximately 50% of the total magnitude of the underestimation. The procedure
      manual for the National Nutrition Survey requests the participants to
      individually weigh the amount of boiled rice taken by family members in the
      household. However, this procedure is not observed in many actual settings.
      Therefore, following this procedure would be an effective measure to improve the
      accuracy of the dietary data.

PMID- 11575576
TI  - Effects of tomato juice consumption on plasma and lipoprotein carotenoid
      concentrations and the susceptibility of low density lipoprotein to oxidative
      modification.
AB  - Effects of tomato juice supplementation on the carotenoid concentration in
      lipoprotein fractions and the oxidative susceptibility of LDL were investigated
      in 31 healthy Japanese female students. These subjects were randomized to one of
      three treatment groups; Control, Low and High. The Control, Low and High groups
      consumed 480 g of a control drink, 160 g of tomato juice plus 320 g of the
      control drink, and 480 g of tomato juice, providing 0, 15 and 45 mg of lycopene,
      respectively, for one menstrual cycle. The ingestion of tomato juice, rich in
      lycopene but having little beta-carotene, increased both lycopene and beta
      carotene. Sixty-nine percent of lycopene in plasma was distributed in the LDL
      fraction and 24% in the HDL fraction. In the Low group, the lycopene
      concentration increased 160% each in the VLDL+IDL, LDL and HDL fractions
      (p<0.01). In the High group, the lycopene concentration increased 270% each in
      the VLDL+IDL and LDL fractions, and 330% in the HDL fraction (p<0.01). Beta
      carotene also increased 120% and 180% in LDL fractions of the Low and the High
      groups, respectively. Despite these carotenoid increases in LDL, the lag time
      before oxidation was not prolonged as compared with that of the Control group.
      The propagation rate decreased significantly after consumption in the High group.
      Multiple regression analysis showed a positive correlation between lag time
      changes and changes in the alpha-tocopherol concentration per triglyceride in
      LDL, and a negative correlation between propagation rate changes and changes in
      the lycopene concentration per phospholipid in LDL. These data suggest that alpha
      tocopherol is a major determinant in protecting LDL from oxidation, while
      lycopene from tomato juice supplementaion may contribute to protect phospholipid
      in LDI, from oxidation. Thus, oral intake of lycopene might be beneficial for
      ameliorating atherosclerosis.

PMID- 11575578
TI  - Investigation of gene expressions related to cholesterol metabolism in rats fed
      diets enriched in n-6 or n-3 fatty acid with a cholesterol after long-term
      feeding using quantitative-competitive RT-PCR analysis.
AB  - We have developed a method to quantitate hepatic apolipoprotein (apo) B, LDL
      receptor, 3-hydroxy-3-methylglutary coenzyme A reductase (HMG-CoA reductase) and
      cholesterol 7alpha-hydroxylase mRNA expression in rats fed a cholesterol-enriched
      diet after long-term feeding using competitive RT-RCR. Rats (8 wk of age) fed a
      conventional diet were shifted to diets containing 10% perilla oil (PEO, oleic
      acid+linoleic acid+alpha-linolenic acid), borage oil (BRO, oleic acid+linoleic
      acid+gamma-linolenic acid), evening primrose oil (EPO, linoleic acid+gamma
      linolenic acid), mixed oil (MIO, oleic acid+linoleic acid+gamma-linolenic
      acid+alpha-linolenic acid), or palm oil (PLO, palmitic acid+oleic acid+linoleic
      acid) with 0.5% cholesterol for 15 wk. There were no significant differences in
      the food intake and body weight gain among the groups. The liver weight in the
      PEO and PLO groups was significantly higher than other groups. The serum total
      cholesterol and very low density lipoprotein (VLDL)+intermediate density
      lipoprotein (IDL)+low density lipoprotein (LDL)-cholesterol concentrations were
      consistently higher in PLO group than in the other groups. The serum high density
      lipoprotein cholesterol concentration was significantly lower in the PEO group
      than in the other groups. The liver cholesterol concentration group was
      significantly higher in the PEO than in the other groups. There were no
      significant differences in the hepatic LDL receptor mRNA level among the groups.
      Hepatic apo B, HMG-CoA reductase and cholesterol 7alpha-hydroxylase mRNA levels
      were not affected by the experimental conditions. However, hepatic cholesterol
      7alpha-hydroxylase mRNA level in the PEO and MIO groups tended to be higher than
      in the other groups. The fecal cholesterol extraction was significantly higher in
      the MIO and PLO groups than in the PEO and EPO groups and the total bile acid
      extraction was significantly higher in the PEO and MIO groups than in the PLO
      group. The results of this study demonstrated that both n-6 fatty acid and n-3
      fatty acids such as gamma-linolenic acid and alpha-linolenic acid lowered serum
      total cholesterol and VLDL+IDL+LDL-cholesterol concentrations of rats in the
      presence of excess cholesterol in the diet compared with dietary saturated fatty
      acid.

PMID- 11575579
TI  - The nutritional status of elderly bed-ridden patients receiving tube feeding.
AB  - Long-term enteral feeding by tube has become a frequently used procedure in
      elderly patients. However, only a few studies dealing with the nutritional
      assessment of such patients are currently available. This study was designed to
      clarify this issue. Anthropometric and biochemical variables, energy expenditure
      and dietary intake were investigated in 44 hospitalized bed-ridden patients with
      and without tube feeding over 65 years of age and 41 age-matched free-eating
      elders in a nursing home. All patients with tube feeding received enteral
      nutrition by nasogastric tube. The body weight, body mass index, mid-upper-arm
      circumference, arm muscle circumference and serum level of albumin were
      significantly lower in the patients with and without tube feeding, compared with
      free-eating elders of both genders (p<0.05). Energy intakes of the patients with
      tube feeding were 1,171+/-286 kcal/d (about 26 kcal/kg/d), which is comparable to
      the predicted total energy expenditure (1.2 x basal energy expenditure). Protein
      intake was 44.9+/-13.1 g/d (about 1.0 g/kg/d) and the percentage of protein per
      total energy was 15%. These intakes are generally considered to be optimal for
      bed-ridden patients receiving tube feeding. However, the incidence of protein
      malnutrition, as evidenced by decreased arm muscle circumference (<80% of normal)
      and hypoalbuminemia (<35 g/L), in the patients with tube feeding was
      significantly higher than that in the healthy elders. In addition, the orally fed
      bed-ridden patients were also malnourished, suggesting that the bed-ridden
      patients easily became malnourished even if they were fed energy and protein
      which approximated calculated predicted values. These findings raise a problem
      concerning nutritional management of bed-ridden patients.

PMID- 11575580
TI  - Effect of dietary seal and fish oils on lipid metabolism in hamsters.
AB  - Eicosapentaenoic and docosahexaenoic acids were distributed mainly in the sn-1
      and 3 positions of seal oil triacylglycerols and in the sn-2 position of fish oil
      triacylglycerols. Seal oil-rich or fish oil-rich fats having constant
      polyunsaturated (PUFAs)/monounsaturated/saturated fatty acids and n-6/n-3 PUFAs
      ratios were fed to hamsters for 3 weeks. The control fat contained linoleic acid
      as the sole PUFA. The concentration of triacylglycerols in the liver was
      significantly lower in the fish oil group than in the control group. Phospholipid
      concentration in serum was lower and that in the liver was higher in the seal oil
      group compared with the fish oil group. The activities of fatty acid synthase
      (FAS), glucose-6-phosphate dehydrogenase (G6PDH), and the malic enzyme were
      significantly lower in both the fish and seal oil groups than in the control
      group. Dietary seal oil more effectively reduced arachidonic acid content in
      liver phosphatidylcholine and phosphatidylethanolamine and serum
      phosphatidylcholine than fish oil. These results showed that different
      intramolecular distribution of n-3 PUFAs influenced glycerolipid metabolism and
      arachidonic acid content in serum and liver phospholipids of hamsters.

PMID- 11575581
TI  - Quantitative evaluation of selenium contained in tea by high performance liquid
      chromatography.
AB  - For determination of selenium (Se) in biological materials, an improved method
      based on high performance liquid chromatographic determination of the fluorophore
      formed by reaction of selenite with 2,3-diaminonapththalene was developed. The
      concentration detection limits were 0.5 ng/g in dried materials and 0.03 ng/mL in
      fluid materials. In quadruplicate assays of 11 biological reference materials
      using the proposed method, measured Se concentrations were not significantly
      different from their certified values. Thus, the proposed method is reliable and
      suitable for the determination of trace levels of Se in foods. Using the proposed
      method, Se concentrations in various kinds of tea were determined to assess the
      contribution of tea to daily Se intake in the Japanese population. Se
      concentration in the leaves of general black, green and oolong tea obtained in
      local retail stores was 33 +/- 19 ng/g (n=440). The leaves of a particular
      Chinese green tea sold under the name "high Se tea" were found to contain 455 +/-
      184 ng/g (n= 14) of Se. While the percentage of Se extractable by infusion was
      less than 5% for the general teas, that in the high Se tea was more than 20%.
      These results indicated that intake of tea does not contribute to daily Se intake
      in the Japanese population. However, since infusions from high Se tea contained
      over 5 ng/mL of Se, consumption of over 1 L/d of tea derived from such high Se
      teas may increase the daily Se intake by close to 10%.

PMID- 11575582
TI  - Effect of dietary cabbage fermentation extract and young barley leaf powder on
      immune function of Sprague-Dawley rats.
AB  - We investigated dietary effects of cabbage fermentation extract (CFE) and young
      barley leaf powder (YBLP) on rat immune functions. Male Sprague-Dawley rats of 4
      wk age were fed for 3 wk diets containing these samples at 0.1 or 1% level. After
      the feeding period, serum IgG level was significantly higher in the rats fed 1%
      CFE. IgG productivity of spleen lymphocytes was enhanced dose-dependently in both
      groups of CFE and YBLP. Furthermore, IgG productivity of mesenteric lymph node
      (MLN) lymphocytes was approximately 2 times higher in the rats fed 1% CFE diet
      than in the control ones. IgA productivity of MLN lymphocytes tended to increase
      in both of CFE and YBLP groups. From these results, it was suggested that dietary
      CFE and YBLP reinforced Ig productivity in both systemic and intestinal immune
      systems. Moreover, CFE feeding tended to enhance the production of TNF-alpha by
      spleen lymphocytes. In spleen phospholipids, the level of arachidonic acid, a
      substrate for inflammatory lipid mediators, was not affected by CFE or YBLP
      feeding.

PMID- 11575583
TI  - Purification and properties of L-gulono-1,4-lactone oxidase from Grifola
      frondosa.
AB  - L-Gulono-1,4-lactone oxidase activity was detected in G. frondosa: therefore its
      properties were studied after purification. A 766-fold purified preparation of
      the enzyme from fresh fruit bodies was obtained by means of a seven-step
      procedure, the overall yield being 14%. The purified enzyme gave a single band on
      polyacrylamide gel electrophoresis and its absorption spectrum exhibited the
      characteristic of a flavoenzyme. The enzyme produced L-ascorbic acid and H2O2,
      with L-gulono-1,4-lactone (GL) as the substrate and oxygen as the electron
      acceptor, and was optimally active at around pH 7.0 and 45 degrees C. Its
      molecular mass was determined to be 250 kDa on gel filtration, while the
      dissociated enzyme exhibited a molecular mass of 69 kDa on SDS-polyacrylamide gel
      electrophoresis, but the true molecular weight is unknown because of the trypsin
      treatment in the purification process. The apparent Km value for GL was 24+/-1
      mM. Its substrate specificity was extremely high and, assuming that for GL to be
      100, the following results were obtained: D-mannono-, 25: D-glucono-, 4; L-idono
      , 3; L-galactono-1,4-lactone, 2; and 15 other lactones tested, 0. It is presumed
      that this enzyme is similar to animal GL-oxidase, ascomycetes D-arabinonolactone
      oxidase, etc.

PMID- 11575584
TI  - Increased conversion ratio of tryptophan to niacin by dietary di-n
      butylphthalate.
AB  - We reported that the growth promoting activity of di-n-butylphthalate (DBP) was
      observed when rats were fed with a niacin-free and tryptophan-limiting diet
      (Shibata et al.. 1982. J Nutr Sci Vitaminol 28, 173-177). The present experiment
      was performed to investigate whether this phenomenon is attributable to the
      increase in the conversion ratio of tryptophan to niacin. The weaning rats were
      fed with a 10% (low protein diet) or 20% protein (conventional protein diet) diet
      with or without adding 1% DBP. The conversion ratio of tryptophan to niacin was
      significantly higher in the DBP group than in the control group; for 10% casein
      diets, it increased two-fold and for 20% casein diet, about five-fold. From these
      results, the previous finding is possibly explained by DBP increasing the
      conversion ratio of tryptophan to niacin.

PMID- 11575585
TI  - Effect of triacylglycerols containing medium- and long-chain fatty acids on body
      fat accumulation in rats.
AB  - Effect of triacylglycerols containing medium- and long-chain fatty acids (TML) on
      body fat accumulation was studied in rats. Male Wistar rats were fed an
      experimental diet containing 25% soybean oil or TML for 6 weeks. The food intake
      for 6 weeks did not significantly differ between the two diet groups. However,
      the perirenal and mesenteric adipose tissue weight and carcass fat content were
      significantly lower in the TML diet group than in the soybean oil diet group. The
      epididymal adipose tissue weight and liver triacylglycerol content did not
      significantly differ between the two diet groups. The digestibility of dietary
      fat did not significantly differ between the two diet groups. These results
      suggest that an intake of TML decreases body fat accumulation compared to an
      intake of soybean oil in rats.

PMID- 11575586
TI  - Antibacterial compounds of licorice against upper airway respiratory tract
      pathogens.
AB  - The antibacterial activity of compounds obtained from licorice was measured
      against upper airway respiratory tract bacteria such as Streptococcus pyogenes,
      Haemophilus influenzae and Moraxella catarrhalis. Among the tested compounds,
      licoricidin exhibited the highest activity against all tested microorganisms with
      an MIC of 12.5 microg/mL. Three coumarin derivatives, glycyrol, glycyrin and
      glycycoumarin also showed antibacterial activity.

PMID- 11575587
TI  - Differential effects of left and right cerebral vascular accidents on language
      competency.
AB  - While language facility was once considered to be the sole province of the
      "dominant" left hemisphere, clinical and experimental findings suggest the right
      hemisphere plays an equally important role in many language tasks. To elucidate
      differential hemispheric language processes, Right Hemisphere Language Battery
      and Western Aphasia Battery data from left (LHD) and right (RHD) hemisphere
      cerebral vascular accident (CVA) patients and controls were subjected to
      multivariate discriminant analysis. The highly significant group differences and
      overall 95% classification rate obtained confirms the utility of the dependent
      measures in differential diagnosis. Results suggest CVA patients experience
      disparate language deficits, with the LHD group experiencing concordant
      convergent language deficits and the RHD group displaying discordant-divergent
      deficits that interfere with the receptive and expressive language skills
      necessary for successful social discourse.

PMID- 11575588
TI  - Depression in multiple sclerosis: relationship to planning ability.
AB  - Recent research has demonstrated deficits on effortful executive tasks involving
      planning in multiple sclerosis (MS) patients. Given the high prevalence of
      depression in MS and the commonly reported link between depression and
      performance on executive tasks, planning impairments in MS may be associated with
      depression. We compared the performance of depressed and nondepressed MS patients
      on a planning task (Tower of London-TOL) to evaluate this hypothesis. Compared
      with nondepressed MS patients, depressed MS patients made significantly (p < .05)
      more moves and took more time per trial on the TOL. A follow-up regression
      analysis was conducted that included the TOL and speeded attentional/working
      memory task indices found to be associated with depression in MS from the
      authors' prior reports. This analysis revealed that 25% of the variance in
      depression scores was predicted by the most sensitive speeded attentional/working
      memory task. Furthermore, this variance overlapped completely with variance
      predicted by the TOL-time/trial index. The only clearly nonspeeded task index,
      TOL-moves per trial, was associated with unique variance (8%) in predicting MS
      depression scores. These results suggest that slowed information processing speed
      and, secondarily, deficient nonspeeded central executive skill, may be core to
      the cognitive deficits characteristic of depressed MS patients.

PMID- 11575589
TI  - Ecologic validity in neuropsychological assessment: prediction of wayfinding.
AB  - This study compared the ability of clinical and ecologic simulation measures to
      predict performance on environment-specific criterion measures of wayfinding.
      Thirty-one unilateral stroke participants comprised the right and left hemisphere
      groups (16 patients with left sided and 15 patients with right sided strokes).
      Participants completed a battery of clinical tasks (e.g., traditional paper-and
      pencil measures of visualization, mental rotation, visual memory and spatial
      orientation), ecologic simulations (e.g., slide route recall and visualization of
      a model town from differing perspectives) and environment specific criterion
      tasks (e.g., route recall and directional orientation). The groups were
      equivalent in age, sex, education, handedness, and weeks since stroke. Both
      ecologic simulation tasks were found to have fairly good internal consistency and
      1 simulation task was significantly related to real world wayfinding. Of the
      clinical tasks, 1 visual memory test was correlated with a directional
      orientation criterion task, but none correlated with route navigation ability.
      Results are consistent with literature purporting the benefits of ecologic
      simulation tasks as predictors of real world functioning.

PMID- 11575590
TI  - Attentional-inhibitory control and social-behavioral regulation after childhood
      closed head injury: do biological, developmental, and recovery variables predict
      outcome?
AB  - Attentional-inhibitory control and social-behavioral regulation are two outcome
      domains commonly impaired after childhood closed head injury (CHI). We compared
      neuropsychological tests of attentional-inhibitory control (vigilance, selective
      attention, response modulation) and social discourse and intentionality
      (inferencing, figurative language, and speech acts) with parent ratings of
      attention and behavioral regulation in relation to four injury-related variables:
      age at CHI, time since CHI, CHI injury severity, and frontal lobe injury
      moderated by CHI severity. Participants were 105 school-aged children in the
      chronic stage of CHI, divided into mild, moderate, and severe injury severity
      groups, and further subdivided according to frontal lobe injury. Outcome indices
      were imperfectly correlated in the group as a whole, although several relations
      between neurocognitive tests and parent ratings were observed within CHI
      subgroups. Different domains of cognitive function had different predictors. For
      attentional-inhibitory control, age at injury and time since injury were most
      predictive of outcome; for social discourse, predictors were injury severity and
      frontal lobe injury moderated by injury severity. Variability in cognitive
      outcome after childhood CHI is not random, but appears related to age, time, and
      biological features of the injury.

PMID- 11575591
TI  - Sensitivity and specificity of standardized neurocognitive testing immediately
      following sports concussion.
AB  - Neuropsychology, with its emphasis on standardized and empirically based methods,
      has made a number of scientific contributions to address growing concerns about
      concussions resulting from sports injuries. This study employs a test-retest
      paradigm to determine the immediate effects of concussion in high-school and
      college athletes. The Standardized Assessment of Concussion (SAC) was
      administered to 1,313 male athletes prior to the beginning of the competitive
      season. Reliable change indices and multiple regression models were computed on
      retest scores obtained from 68 noninjured athletes who were readministered the
      SAC at either 60 or 120 days following baseline testing. Receiver operating
      characteristic (ROC) curve analyses were used to test these models with data
      obtained on 50 athletes tested immediately following concussion. The results
      indicate that a decline of I point on the SAC at retesting classified injured and
      noninjured participants with a level of 94% sensitivity and 76% specificity. The
      RCI and multiple regression models provided comparable levels of group
      classification, but provided cut-offs that are conservative for use with this
      population. The results support and extend previous research findings indicating
      that the SAC is a valid instrument for detecting the immediate effects of mild
      traumatic brain injury.

PMID- 11575592
TI  - Menstrual effects on asymmetrical olfactory acuity.
AB  - Gender specific discrepancies on psychometric examination are often interpreted
      to reflect static differences in cerebral hemisphere specialization, but dynamic
      alterations relating to circulating gonadal hormones may also be relevant after
      puberty. The often cited inference of a right hemisphere advantage in males and
      left hemisphere advantage in females derived from small but reliable differences
      on spatial tasks and verbal tasks, for example, may to some extent relate to
      gender-specific differences in circulating gonadal hormones. Performance
      fluctuations on other higher order cognitive tasks through the menstrual cycle
      tend to support a temporal association between alterations in cerebral laterality
      and hormone fluctuations. A potential left hemisphere advantage after
      menstruation when estrogen and progesterone levels are high in contrast to a
      right hemisphere advantage at menstruation when estrogen and progesterone levels
      are low has also received support from shifts in visual field perception. The
      present investigation continues this line of work by measurement of prospective
      changes in unirhinal olfactory acuity in the menstrual, ovulatory, and midluteal
      phases of the menstrual cycle in 11 healthy women who agreed to blood assays of
      estradiol and progesterone prior to completing a modified version of the
      Connecticut Chemosensory Perception Exam (CCPE). The CCPE detection of n-butanol
      showed a clear pattern of changes over the menstrual cycle marked by an asymmetry
      favoring the right nostril during menstruation when estradiol and progesterone
      levels were low, an asymmetry favoring the left nostril during ovulation when
      estradiol levels were high and progresterone levels were low, and an absence of
      asymmetry during the midluteal phase when estradiol levels decreased and
      progesterone levels increased. Preliminary correlation analyses revealed a
      potential competitive influence of estradiol and progesterone on this apparent
      shift in cerebral laterality. There is thus sufficient evidence to conclude that
      dynamic changes in relative cerebral hemisphere advantages have a temporal
      relation to fluctuations in circulating gonadal hormones and to suggest the value
      of additional investigation of more specific causal relations.

PMID- 11575593
TI  - Striatal contributions to category learning: quantitative modeling of simple
      linear and complex nonlinear rule learning in patients with Parkinson's disease.
AB  - The contribution of the striatum to category learning was examined by having
      patients with Parkinson's disease (PD) and matched controls solve categorization
      problems in which the optimal rule was linear or nonlinear using the perceptual
      categorization task. Traditional accuracy-based analyses, as well as quantitative
      model-based analyses were performed. Unlike accuracy-based analyses, the model
      based analyses allow one to quantify and separate the effects of categorization
      rule learning from variability in the trial-by-trial application of the
      participant's rule. When the categorization rule was linear, PD patients showed
      no accuracy, categorization rule learning, or rule application variability
      deficits. Categorization accuracy for the PD patients was associated with their
      performance on a test believed to be sensitive to frontal lobe functioning. In
      contrast, when the categorization rule was nonlinear, the PD patients showed
      accuracy, categorization rule learning, and rule application variability
      deficits. Furthermore, categorization accuracy was not associated with
      performance on the test of frontal lobe functioning. Implications for
      neuropsychological theories of categorization learning are discussed.

PMID- 11575594
TI  - Encoding and complex figure recall.
AB  - This study investigated the effects of type of encoding strategy (organized and
      disorganized) and of active versus passive encoding on memory for interrelated
      spatial material. Delayed recall performance for a complex, nonrepresentational
      two dimensional figure was measured in 120 normal young adults assigned to one of
      three groups that varied as to the approach used during the initial construction
      of the figure. Those applying self-generated strategies performed best. In
      addition, recall performances were significantly better for those applying a
      prescribed, organized strategy as compared with performances of those applying a
      prescribed, disorganized strategy. These effects were not attributable to
      differences on measures of IQ or spatial information processing. The findings
      indicated that, independent of memory ability, both the degree of organization
      and of active strategizing at encoding are determinants of recall ability for
      complex spatial information and suggest that these factors have implications for
      memory processes more generally.

PMID- 11575595
TI  - Attention problems in adolescents with congenital hypothyroidism: a
      multicomponential analysis.
AB  - Even though early treatment of congenital hypothyroidism (CH) with newborn
      screening prevents the mental retardation previously seen in cretinism, affected
      children still exhibit subtle persisting neurocognitive deficits. One of their
      commonest problems is poor attention, which reflects both early disease severity
      and later (high) circulating thyroid hormone levels. While attention is currently
      regarded as multicomponential in nature, with different processing components
      supported by different brain regions, the specific components of attention
      affected by CH have not been identified. In light of animal evidence showing that
      neonatal thyroid hormone deficiencies impede the neurodevelopment of structures
      important for selective aspects of attention, we proposed a multicomponential
      approach to study attention in children with CH. This was accomplished via
      retrospective analysis of existing data on adolescents with CH whose attention
      was previously evaluated using multiple tests. Results showed significantly
      poorer overall attention in CH than controls with differences occurring mainly on
      focus and inhibit indices. However, performance on various indices was associated
      with different disease parameters. Poor encode and focus were correlated with
      more severe hypothyroidism and a longer period of thyroid hormone insufficiency
      and poor select and shift with higher thyroid hormone levels at testing. These
      results signify that thyroid hormone is important for the development and later
      regulation of brain structures supporting distinct aspects of attention.

PMID- 11575596
TI  - Inflammatory and hormonal measures predict neuropsychological functioning in
      systemic lupus erythematosus and rheumatoid arthritis patients.
AB  - Abnormalities of inflammatory and hormonal measures are common in SLE patients.
      Although cognitive dysfunction has been documented in SLE patients, the
      biological mechanism of these deficits has not been clarified. The goal of this
      study was to explore the relationship between inflammatory and hormonal activity
      and measures of learning, fluency, and attention in systemic lupus erythematosus
      patients without neuropsychiatric symptoms (non-CNS-SLE), patients with
      rheumatoid arthritis (RA), and healthy controls (HC). Fifteen non-CNS-SLE
      patients, 15 RA patients and 15 HC participants similar in age, education, and
      gender (female) were compared on tests of cognition, depression, and plasma
      levels of interleukin-6 (IL-6), dehydroepiandrosterone (DHEA),
      dehydroepiandrosterone sulfate (DHEA-S) and cortisol. Non-CNS-SLE patients
      demonstrated lower learning and poorer attention. Furthermore, non-CNS-SLE and RA
      patients had significantly lower levels of DHEA and DHEA-S than HC participants.
      Hierarchical regression analysis demonstrates that DHEA-S and IL-6 accounts for a
      unique portion of the variance in subject performance on measures of learning and
      attention after controlling for depression and corticosteroid treatment. This
      data highlights the value of hierarchical analyses with covariates, and provides
      evidence in humans of a relationship between peripheral cytokine levels and
      cognitive function.

PMID- 11575597
TI  - Bidirectional child-family influences on outcomes of traumatic brain injury in
      children.
AB  - Child behavior problems, injury-related family burden, and parent psychological
      distress were assessed longitudinally over the first year post injury in 40
      children with severe traumatic brain injury (TBI), 52 with moderate TBI, and 55
      with orthopedic injuries not involving brain insult. Parents rated children's
      preinjury behavior soon after injury. Postinjury child behavior and family
      outcomes were assessed at 6- and 12-month follow-ups. Findings from path analysis
      revealed both direct and indirect effects of TBI on child behavior and family
      outcomes, as well as cross-lagged child-family associations. Higher parent
      distress at 6 months predicted more child behavior problems at 12 months,
      controlling for earlier behavior problems; and more behavior problems at 6 months
      predicted poorer family outcomes at 12 months, controlling for earlier family
      outcomes. Support for bidirectional influences is tentative given that limited
      sample size precluded use of structural equation modeling. The findings
      nevertheless provide impetus for considering the influences of person-environment
      interactions on outcomes of TBI.

PMID- 11575598
TI  - CADASIL: neuropsychological findings in three generations of an affected family.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is a hereditary brain disease with a variety of
      neurologic and psychiatric manifestations. We studied 3 members of a family who
      each had leukoencephalopathy on neuroimaging studies and a characteristic
      mutation for CADASIL in the notch 3 region of chromosome 19q12. In all 3 cases,
      neurobehavioral impairment dominated the clinical picture, and a pattern of
      psychiatric dysfunction heralding cognitive decline emerged. Neuropsychological
      evaluation revealed diverse deficits, but a profile of frontal lobe dysfunction,
      declarative memory impairment suggestive of a retrieval deficit, and relatively
      preserved language was evident. These cases provide a cross-sectional study of
      the evolution of CADASIL, and suggest that, as in other diseases characterized by
      white matter dementia, psychiatric dysfunction may occur initially, followed by
      pervasive cognitive dysfunction later in the course of the disease. CADASIL
      should be considered in young adults with unexplained leukoencephalopathy on
      neuroimaging studies, and in those with neurobehavioral dysfunction and a
      suggestive family history.

PMID- 11575599
TI  - Emotional deficit as a neuropsychopathological disturbance in HIV infection.

PMID- 11575600
TI  - The ketogenic diet: an effective medical therapy with side effects.

PMID- 11575601
TI  - Increased medial thalamic choline in pediatric obsessive-compulsive disorder as
      detected by quantitative in vivo spectroscopic imaging.
AB  - The thalamus has been implicated in the pathophysiology of obsessive-compulsive
      disorder. Using a multislice spectroscopic imaging sequence, we reported
      reductions in right and left medial thalamic N-acetylaspartate/cytosolic choline
      + creatine/phosphocreatine and N-acetylaspartate/cytosolic choline levels in 11
      pediatric patients with obsessive-compulsive disorder, 8 to 15 years, versus 11
      case-matched healthy controls. These changes may reflect a change in N
      acetylaspartate, cytosolic choline, or creatine concentrations. Therefore, using
      a validated phantom replacement methodology, we obtained absolute measures
      (mmol/L) of N-acetylaspartate, a putative marker of neuronal viability, cytosolic
      choline, and creatine in these subjects. A significant increase in cytosolic
      choline was observed in right and left medial but not lateral thalami in patients
      with obsessive-compulsive disorder versus controls. N-acetylaspartate and
      creatine did not differ significantly between case-control pairs in the medial or
      lateral thalamus. These findings provide new evidence of cytosolic choline
      abnormalities in the thalamus in pediatric obsessive-compulsive disorder.

PMID- 11575602
TI  - Carnitine-deficient myopathy as a presentation of tyrosinemia type I.
AB  - Carnitine deficiency secondary to renal Fanconi's tubulopathy has been described
      in only a few inborn errors of metabolism: cystinosis, galactosemia, and Fanconi
      Bieckel syndrome. We report a 27-month-old infant who presented with a sudden
      change in gait owing to proximal muscle weakness. The laboratory evaluation
      showed carnitine deficiency associated with Fanconi's tubulopathy. Eventually,
      tyrosinemia type I was diagnosed. Carnitine deficiency can contribute to the
      clinical picture of hepatorenal tyrosinemia and should therefore be evaluated and
      treated.

PMID- 11575603
TI  - Profile of referrals for early childhood developmental delay to ambulatory
      subspecialty clinics.
AB  - The objective of this study was to determine the profile and pattern of referral
      to subspecialty clinics of young children with suspected developmental delay
      together with the factors prompting their referral. All children under 5 years of
      age referred to either developmental pediatrics or pediatric neurology clinics at
      a single tertiary hospital over an 18-month period were prospectively identified.
      Standardized demographic and referral information were collected at intake, final
      developmental delay subtype diagnosed was identified, and referring physicians
      were surveyed regarding factors prompting referral. A total of 224 children met
      study criteria. There was a marked male preponderance (166/224), especially among
      those with either cognitive or language delay. Two delay subtypes, global
      developmental delay and developmental language disorder, accounted for two thirds
      of the diagnoses made. For slightly more than one third of the children (75/224),
      the delay subtype diagnosed following specialty evaluation was different from
      that initially suspected by the referring physician. A mean delay of 15.5 months
      was observed for the cohort as a whole between initial parental concern and
      specialty assessment. For referring physicians, the major factor prompting
      referral was the severity of the observed delay. The most important aspects of
      the specialty evaluation according to referral sources were the identification of
      a possible etiology and confirmation of delay. A profile of referrals and the
      rationale thereof for a cohort of children with suspected developmental delay is
      presented that, although locale specific, has implications for service provision
      and training.

PMID- 11575604
TI  - Prenatal and perinatal determinants of neonatal seizures occurring in the first
      week of life.
AB  - To evaluate prenatal and perinatal risk factors for early neonatal seizures, we
      conducted a case-control study including 100 newborns with neonatal seizures in
      the first week of life and 204 controls randomly selected from a list of healthy
      newborns born in the same hospital during the study period. Generalized tonic
      seizures were the most common seizures observed (29%), although the majority of
      newborns (71%) experienced more than one type of seizure. The most frequent
      presumed etiology of neonatal seizures was hypoxic-ischemic encephalopathy (30%).
      A history of epilepsy in first-degree relatives was found only for cases.
      Neonatal seizures were found to be associated with maternal disease in the 2
      years before pregnancy, mother's weight gain > 14 kg during pregnancy, placental
      pathology, preeclampsia, low birthweight, low gestational age, and jaundice in
      the first 3 days of life. The need for cardiopulmonary resuscitation was found
      only for cases (37%). The causal pathways for neonatal seizures often begin
      before birth, and some of the factors identified may be preventable.

PMID- 11575605
TI  - Schistosomiasis in Madagascar.

PMID- 11575606
TI  - Lactic acid elevation in extramitochondrial childhood neurodegenerative diseases.
AB  - We report three children, each of whom seemed to have a primary mitochondrial
      disorder at presentation but was eventually diagnosed with an extramitochondrial
      inherited metabolic disease. The first patient presented at 6 months with
      developmental delay. Magnetic resonance imaging showed an abnormal signal in the
      white matter, and magnetic resonance spectroscopy showed elevated lactate peaks.
      A muscle biopsy showed complex IV deficiency, but leukocyte measurement of
      galactosylceramide beta-galactosidase activity was markedly diminished,
      consistent with Krabbe's disease. The second patient presented at birth with
      seizures and later had developmental delays. There was brain atrophy on
      neuroimaging. Serum and cerebrospinal fluid lactate levels were elevated. She had
      persistently elevated urine thiosulfate, which was diagnostic for molybdenum
      cofactor deficiency. The third child presented at 2 months with seizures and
      hypotonia. Magnetic resonance imaging showed an abnormal signal in the basal
      ganglia and surrounding white matter, whereas magnetic resonance spectroscopy
      showed elevated lactate peaks. A brain biopsy was diagnostic for Alexander's
      disease. These cases and others in the literature suggest that lactic acid
      elevation in the central nervous system can be found in a number of
      extramitochondrial neurologic diseases. Such diseases would constitute a third
      category of lactic acidosis.

PMID- 11575607
TI  - Comparison of electroencephalographic dipoles of interictal spikes from prolonged
      scalp video-electroencephalography and magnetoencephalographic dipoles from short
      term recording in children with extratemporal lobe epilepsy.
AB  - We retrospectively compared electroencephalographic (EEG) dipoles of interictal
      spikes from prolonged video-EEG monitoring with magnetoencephalographic dipoles
      from short-term recording in four children with extratemporal lobe epilepsy. We
      analyzed both sets of dipoles using individual interictal spikes and single
      moving dipole modeling and evaluated the profiles of spike appearance, dipole
      position, and orientation in EEG and magnetoencephalography. We obtained more
      than 100 magnetoencephalographic spikes in two patients who manifested frequent
      interictal EEG spikes throughout both day and night but fewer than 40
      magnetoencephalographic spikes in two patients who had interictal EEG spikes
      mainly during sleep. The dipole positions of EEG and magnetoencephalography were
      in close proximity and included in the surgical resection area. Most of the
      dipoles between EEG and magnetoencephalography were oriented perpendicularly. A
      combination of EEG dipole analysis from prolonged video-EEG monitoring and
      magnetoencephalographic dipole analysis provides complementary information for
      presurgical evaluation in children with intractable extratemporal lobe epilepsy.

PMID- 11575608
TI  - Clinical correlates of white-matter abnormalities on head magnetic resonance
      imaging.
AB  - We undertook this study to investigate the relationship between white-matter
      abnormalities (seen on brain magnetic resonance imaging [MRI]) and muscle tone
      and muscle stretch reflexes on clinical examination. We identified all patients
      less than 5 years of age who had undergone cranial MRI studies at Riley Hospital
      for Children between June 30, 1999, and July 1, 2000, whose scans were read as
      showing white-matter abnormalities. We measured two ratios and the thickness of
      the corpus callosum as indicators of the quantity of cerebral white matter. The
      ratios were R1, the ratio of the thickness of the white matter at the level just
      above the body of the lateral ventricle compared with the width of the
      hemisphere, and R2, the ratio of the thickness of the white matter to the width
      of the hemisphere at the level of the trigone of the lateral ventricle. The
      thickness of the corpus callosum was measured at the junction of the anterior two
      thirds and the posterior third. We also evaluated the signal intensity of the
      cerebral white matter by reviewing the fluid-attenuated inversion-recovery images
      and grading the signal as normal to severely abnormal depending on the degree and
      extent of high signal intensity seen (0 = normal to 4+). Thirty-eight children
      less than 5 years of age who underwent MRI scans between June and August 2000 and
      who were found to have normal tone prospectively and normal MRI scan on review
      served as a control group. We identified 215 patients who had white-matter
      abnormalities; of these, only 142 (66%) had documented tone assessments in their
      medical record. Our study group was divided into three groups: increased (n =
      35), decreased (n = 53), and normal tone (n = 54). All three measurements of
      white matter in each of the three study groups were significantly below values
      for control children. The children with white-matter abnormalities and decreased
      tone had significantly less signal intensity abnormality than the other study
      groups. Children with white-matter abnormalities and increased tone had a greater
      frequency of increased reflexes and tended to have more signal abnormalities than
      the other groups. The group of children with white-matter abnormalities and
      normal tone had the least amount of cerebral white-matter deficiency of the three
      study groups. In patients with strikingly decreased quantities of cerebral white
      matter, those with normal signal-intensity white matter are likely to be
      hypotonic with normal reflexes and those with increased signal intensity in the
      white matter are likely to be spastic.

PMID- 11575609
TI  - Acute pancreatitis causing death in a child on the ketogenic diet.
AB  - The ketogenic diet has demonstrated good efficacy in children with
      pharmacologically resistant seizures. Relatively few serious complications have
      been reported in the more than 70 years in which the diet has been used. We
      report a child who developed acute pancreatitis and died. A 9-year-old girl had a
      seizure disorder with associated developmental delay owing to glucose transport
      protein deficiency. The ketogenic diet with medium chain triglyceride oil had
      been initiated shortly after diagnosis in infancy. She was not on
      anticonvulsants. She presented in coma with decreased respiratory effort and
      shock, requiring resuscitation. Investigations were consistent with pancreatitis.
      Despite fluid resuscitation and inotropic support, she had prolonged hypotension
      and acidosis. She subsequently had a cardiac arrest and died. A postmortem
      examination confirmed hemorrhagic pancreatitis. Hypertriglyceridemia is a risk
      factor for developing acute pancreatitis. The high fat content of the ketogenic
      diet often causes hyperlipidemia. The outcome for this patient raises concern
      regarding a potential consequence of the ketogenic diet.

PMID- 11575610
TI  - Central nervous system Sjogren's syndrome in a child: case report and review of
      the literature.
AB  - We describe a case of pediatric Sjogren's syndrome with progressive neurologic
      involvement. At age 4 years, she had been diagnosed with Melkersson-Rosenthal
      syndrome. After being stable with facial diplegia and swelling for 5 years, she
      acutely presented with diplopia, vertigo, and ataxia. Cranial magnetic resonance
      imaging (MRI) showed a left dorsal midbrain lesion. Serologic and histopathologic
      findings confirmed primary Sjogren's syndrome. She responded well to intravenous
      methylprednisolone, with subsequent clinical improvement and MRI resolution. This
      report reviews the pediatric literature and underscores the importance of
      considering Sjogren's syndrome in a child with unexplained facial weakness and in
      the differential diagnosis of pediatric stroke.

PMID- 11575611
TI  - Cavernous hemangioma in a child presenting with hemichorea: response to pimozide.
AB  - The case of a 9-year-old boy with hemichorea due to cavernous hemangioma in the
      left caudate nucleus is presented. To our knowledge, only two children have been
      reported with hemichorea associated with cavernous hemangioma. Hemichorea in our
      patient responded to pimozide, a neuroleptic that blocks central nervous system
      dopaminergic receptors.

PMID- 11575612
TI  - Homocystinuria with transverse sinus thrombosis.
AB  - A case of cerebral venous thrombosis caused by undiagnosed homocystinuria is
      reported. The pitfalls regarding the diagnosis of a potentially medically
      treatable condition are discussed. Cerebral venous thrombosis in children has a
      variable type of onset and a multiplicity of causes. This type of pathology,
      although not frequent, is more common than previously thought. Among the
      different etiologies, undiagnosed homocystinuria is not routinely considered. We
      report a case of venous thrombosis of the left transverse cerebral sinus in a
      girl with drug-resistant partial epilepsy and homocystinuria. This diagnosis was
      considered and confirmed after the appearance of acute cerebral symptoms caused
      by venous thrombosis.

PMID- 11575613
TI  - Optic neuropathy in primary antiphospholipid syndrome in childhood.
AB  - Neurologic symptoms associated with antiphospholipid antibodies in children
      include thrombotic events, unilateral movement disorders, or migraine. We present
      a 7-year-old girl with bilateral optic neuropathy, cerebral white-matter lesions,
      and antiphospholipid IgM that responded to prednisone and tended to relapse when
      it was stopped. Remission was obtained under maintenance corticosteroid therapy,
      and the antiphospholipid antibodies disappeared. This case suggests a role for
      antiphospholipid antibodies in the pathogenesis of optic neuropathy in childhood.

PMID- 11575614
TI  - Optic neuritis: a novel presentation of Schilder's disease.
AB  - The clinical features of a 7-year-old girl who presented with unilateral optic
      neuritis are presented. Magnetic resonance imaging (MRI) showed lesions in the
      affected optic nerve and the centrum semiovale bilaterally. Biopsy of one of the
      cerebral lesions was consistent with a diagnosis of Schilder's disease. Visual
      acuity returned to normal, and the demyelinating MRI lesions improved markedly
      with corticosteroid treatment. Optic neuritis is a novel mode of presentation in
      Schilder's disease.

PMID- 11575615
TI  - Persistence of breath-holding spells into late childhood.
AB  - Breath-holding spells commonly occur during infancy. The disorder represents a
      self-limited, benign phenomenon, and breathholding spells almost always resolve
      by school age. Their continuing occurrence beyond this age is exceedingly
      uncommon and may create diagnostic confusion. We recently encountered an 8-year
      old boy who continues to experience breath-holding spells.

PMID- 11575616
TI  - Visual agnosia after treatment of a posterior fossa ependymoma in a 16-month-old
      girl.
AB  - We present the clinical observation of a 16-month-old girl treated for a
      posterior fossa ependymoma who experienced severe and delayed visual dysfunction.
      She was initially treated by surgery and conventional chemotherapy. When she
      relapsed at age 3 years, the salvage treatment combined high-dose chemotherapy,
      second surgery, and local irradiation. At age 4 years, disturbed gait and
      dysarthric speech appeared rapidly, and she became unable to recognize objects
      and people. Computed tomography revealed bilateral calcifications in the
      cerebellum and temporal and occipital lobes but no relapse. The neuropsychologic
      evaluations revealed signs of visual agnosia and marked intellectual impairment.
      The role of the different treatment modalities in the pathogenesis of this
      unusual syndrome is discussed.

PMID- 11575617
TI  - Concentrations of nucleotides, nucleosides, purine bases, oxypurines, uric acid,
      and neuron-specific enolase in the cerebrospinal fluid of children with sepsis.
AB  - To determine the effects of sepsis on cerebral energy metabolism, the
      cerebrospinal fluid adenosine monophosphate, inosine monophosphate, inosine,
      adenosine, guanosine, hypoxanthine, xanthine, and urate concentrations were
      determined by high-performance liquid chromatography and the neuron-specific
      enolase levels by means of an enzyme immunoassay method in 32 children with
      sepsis, without meningitis, aged between 2 months and 13 years, and in 160 age
      matched controls. The septic group had significantly higher cerebrospinal fluid
      concentrations of inosine, adenosine, xanthine, and urate than controls. These
      results suggest that sepsis could provoke some degree of neuronal hypoxia and
      significant alterations of cerebral energy metabolism homeostasis.

PMID- 11575618
TI  - Evading detection on the MMPI-2: does caution produce more realistic patterns of
      responding?
AB  - Studies on MMPI and MMPI-2 malingering indexes often sacrifice generalizability
      in an attempt to control internal validity. This study improves external validity
      while still maintaining internal validity by providing graduate student
      participants with a realistic context for malingering on the MMPI-2 (n=94) and
      MMPI (n=30). Contextual parameters include a realistic life predicament,
      psychological knowledge, an incentive, the presence versus absence of a specific
      diagnosis, and a caution to be realistic. This study found that cautioning
      participants not to overexaggerate their responses significantly improves their
      ability to evade detection on the MMPI-2 and MMPI. Standard malingering indexes
      (Infrequency, F; Back Side, F, Fb; F-Correction, F-K; and Infrequency
      Psychopathology, F(p)) were insufficiently sensitive in identifying simulators
      using common cutoff scores for these cautious simulators.

PMID- 11575619
TI  - Detection of deception on the Schedule for Nonadaptive and Adaptive Personality:
      validation of the validity scales.
AB  - This study used a simulation design to investigate the validity scales of the
      Schedule for Nonadaptive and Adaptive Personality (SNAP). Undergraduates (N=192)
      were randomly assigned to two positive distortion (PD) groups, two negative
      distortion (ND) groups, and a control group. Controls responded normally, whereas
      the deception groups responded according to assigned characters. Preliminary
      analyses indicated no significant differences within distortion valence; thus,
      the groups were collapsed into single PD (n=76), ND (n=79), and control groups
      (n=37). Mean-level analyses revealed that, consistent with previous studies, ND
      profiles are easier to detect than PD profiles. Cutoff scores were suggested, and
      the classification accuracy of these scores converged with the results of several
      discriminant function analyses to indicate that Rare Virtues and Deviance predict
      group membership at least as well as MMPI-2 validity scales. Structural analyses
      revealed that two moderately correlated factors-positive distortion and negative
      distortion-underlie scores on these validity scales.

PMID- 11575620
TI  - Two- and three-factor solutions of the WAIS-III.
AB  - The third edition of the Wechsler Adult Intelligence Scale manual reports four
      factor solutions for the WAIS-III, and subsequent research has validated four
      factor solutions for a variety of samples. These four factors consistently
      correspond to the four Factor Indexes that are yielded by the WAIS-III. However,
      the WAIS-III still provides Verbal and Performance IQs, in addition to the
      Indexes, making it desirable to examine two-factor solutions as well. In
      addition, because the Wechsler literature includes much interpretation of three
      factor solutions, these solutions were likewise examined. Principal factor
      analysis followed by Varimax and Oblimin rotations of two and three factors were
      performed on data for the total WAIS-III sample ages 16 to 89 years (N=2,450).
      The two-factor solutions were viewed as a construct validation of Wechsler's two
      separate IQs, although the Working Memory subtests tended to load higher on the
      Performance scale than on their intended scale (Verbal); three-factor solutions
      were interpreted within the context of Horn's expanded fluid-crystallized theory
      and research on working memory. Both the two- and three-factor Varimax-rotated
      solutions were related to similar factor analyses conducted previously for the
      Wechsler Adult Intelligence Scale-Revised and the Wechsler Intelligence Scale for
      Children-III. Coefficients of congruence between like-named factors consistently
      exceeded .90, and usually .98, across different Wechsler batteries.

PMID- 11575621
TI  - The utility of MMPI-2 suicide items for assessing suicidal potential: development
      of a Suicidal Potential Scale.
AB  - The assessment of suicidal potential is one of the most challenging and stress
      inducing tasks facing clinicians. Studies that have attempted to identify
      specific MMPI codetypes, scales, or individual items predictive of completed
      suicide have produced inconsistent findings. This study focused on the
      relationship between the six most direct MMPI-2 suicide items (Items 150, 303,
      506, 520, 524, and 530) and verbally reported history of suicidal ideation and
      behavior among a sample of psychotherapy outpatients (n =116). These six MMPI-2
      suicide items provided valuable information regarding suicidal ideation and
      behavior above and beyond that of verbal self-report. These items were grouped
      together to create a single scale, the Suicidal Potential Scale (SPS) that
      manifested strong internal consistency. The SPS provides the clinician with a
      reliable method of assessing for self-reported suicidal ideation and behavior.

PMID- 11575622
TI  - Use of structured self-report assessment to diagnose borderline personality
      disorder during major depressive episodes.
AB  - Diagnosis of borderline personality disorder (BPD) during episodes of major
      depression (MDE), although clinically important, is complicated in several
      respects when using self-report methods. Structured interview data were used to
      select a group of patients with comorbid BPD (n=21) from a sample of outpatients
      presenting with MDE. This group was compared with a group of MDE patients without
      BPD (n=24) and with a group of community controls (n=20) using self-report data
      from the Personality Assessment Inventory (PAI), the revised Personality
      Diagnostic Questionnaire (PDQ), and the Beck Depression Inventory (BDI). Analyses
      revealed that the BPD group obtained significantly higher scores on PAI and PDQ
      scales measuring features of BPD and on the PAI Negative Impression Management
      scale. The severity and type of MDE symptoms reported on the PAI and BDI did not
      differentiate the clinical groups. These data show that useful information for
      the diagnosis of BPD during depressive episodes can be gathered from self-report
      assessment instruments like the PAI.

PMID- 11575623
TI  - Development and validation of the Theoretical Orientation Scale for Clinicians:
      reflecting solution-focused principles.
AB  - This article describes the development and validation of the 40-item Theoretical
      Orientation Scale for Clinicians (TOSCsF), an instrument designed to (a)
      operationalize attitudes towards the principles of solution-focused brief therapy
      (SFBT), and (b) assess clinicians' endorsement of this therapeutic approach.
      Participants (N=284) were members of the National Association of Alcoholism and
      Drug Abuse Counselors (NAADAC) who responded (63%) to a mail questionnaire
      containing the TOSCsF. Reliability (Cronbach's alpha = .82) and validity of
      scores on the TOSCsF are examined in light of the detection of an acquiescent
      response pattern in 40 respondents. A subsequent three-factor structure derived
      from a principal components analysis (accounting for 28% of the variance)
      suggests modest, but positive, support for the construct validity of the TOSCsF.
      Recommendations for further refinement of the instrument are discussed.

PMID- 11575624
TI  - Age at earliest reported memory: associations with personality traits, behavioral
      health, and repression.
AB  - The present study examined relationships between the age at earliest memory and
      the personality traits and behavioral health of 107 undergraduates. Participants
      answered questions on their earliest memory and completed the Myers-Briggs Type
      Indicator (MBTI) and a medical history form. Analyses indicated that continuous
      scores on two MBTI scales (Sensing-Intuition and Judging-Perceiving) were
      inversely related to age at earliest memory as were participant's self-reported
      drug and alcohol problems, emotional and psychological symptoms, accident rates,
      physical symptoms, and satisfaction with health. Respondents who reported first
      memories at or after 7 years of age (i.e., approximately 1 SD above the mean age
      at recalled memory) were classified as repressors. Repressors scored in the
      Sensing and Judging directions on the MBTI and reported significantly fewer
      emotional symptoms, accidents, psychological symptoms, and less health
      satisfaction than nonrepressors. Results are consistent with the age at earliest
      memory and repression literature and support the use of earliest memory age as an
      index of repression.

PMID- 11575625
TI  - Qualitative analysis of verbal fluency output: review and comparison of several
      scoring methods.
AB  - We compared three approaches to scoring qualitative aspects of verbal fluency
      performance in 88 healthy young adults. Phonemic and semantic fluency output was
      scored for word clustering and switching between clusters. Convergent validity
      analyses using other tests presumed to tap into strategy use (California Verbal
      Learning Test, Ruff Figural Fluency Test) support scoring of phonemic and
      semantic clusters on both fluency tasks. Task-discrepant clustering (e.g.,
      semantic clustering on phonemic fluency) may index intentional strategy use on
      both fluency tasks, whereas task consistent clustering (e.g., phonemic clustering
      on phonemic fluency) appears strategic only on semantic fluency. Switching can be
      decomposed into subtypes that appear to reflect different cognitive processes on
      phonemic versus semantic fluency. Principal components analyses suggest that
      earlier scoring methods do not fully capture the "process" aspects of verbal
      fluency performance.

PMID- 11575626
TI  - A comparative view of the new journal: Assessment.
AB  - The reference sections from all articles in the 1997 volumes of Assessment,
      Journal of Personality Assessment, and Psychological Assessment were entered into
      a database and analyzed. An article published in Assessment averaged almost 31
      references. An article published in Journal of Personality Assessment contained
      an average of 33 references. Psychological Assessment averaged 38 references per
      article. The median age of the references in the three journals was 8 years with
      an interquartile range of 4 to 14 years. The Journal of Personality Assessment
      had the largest number of citations in this database of 5,316 references. Each of
      these received a relatively large number of their citations from articles
      published in the same journal (self-citations). Randomly selected articles from
      the 1997 volume of Assessment received fewer citations in the Social Science
      Citation Index than a similar set of articles from the other two journals.
      However, the data on Assessment, when compared with data available on other new
      scientific publications, suggests that Assessment is doing as well as other
      fledgling journals.

PMID- 11575627
TI  - Test-retest reliability of the Advanced Psychodiagnostic Interpretation (API)
      scoring system for the Bender Gestalt in chronic schizophrenics.
AB  - This study assesses the test-retest reliability of the revised Advanced
      Psychodiagnostic Interpretation (API) scoring system for the Bender Gestalt Test
      (BGT). The API system identifies 207 possible distortions in a BGT protocol. Test
      retest reliability for 40 schizophrenic patients tested twice with a mean
      interval of 6.4 years (SD=3.8 years) was good, ranging from .71 to .80. Further
      reliability and validity studies are needed to further demonstrate the
      effectiveness of the system.

PMID- 11575628
TI  - Deviant vocal fold vibration as observed during videokymography: the effect on
      voice quality.
AB  - Videokymographic images of deviant or irregular vocal fold vibration, including
      diplophonia, the transition from falsetto to modal voice, irregular vibration
      onset and offset, and phonation following partial laryngectomy were compared with
      the synchronously recorded acoustic speech signals. A clear relation was shown
      between videokymographic image sequences and acoustic speech signals, and the
      effect of irregular or incomplete vocal fold vibration patterns was recognized in
      the amount of perceived breathiness and roughness and by the harmonics-to-noise
      ratio in the speech signal. Mechanisms causing roughness are the presence of
      mucus, phase differences between the left and right vocal fold, and short-term
      frequency and amplitude modulation. It can be concluded that the use of
      simultaneously recorded videokymographic image sequences and speech signals
      contributes to the understanding of the effect of irregular vocal fold vibration
      on voice quality.

PMID- 11575629
TI  - Vocal tract resonance analysis of aging voice using long-term average spectra.
AB  - This study is the first to use long-term average spectra (LTAS) to investigate
      resonance characteristics of dynamic speech in young adulthood and old age. A
      total of 80 speakers participated, divided equally by age group and gender. All
      elderly speakers were healthy, active members of the community. Measurement of
      the first three spectral peaks in LTAS from the first paragraph of the Rainbow
      Passage revealed significant lowering of peak 1 from young adulthood to old age
      in both men and women. Peaks 2 and 3 also lowered significantly across the adult
      lifespan in women and showed a tendency to lower in men. These acoustic findings
      are consistent with anatomic data suggesting that aging results in lengthening of
      the supraglottic vocal tract. Findings that women demonstrate more substantial
      lowering of spectral peaks with aging than men suggest that women may undergo
      more pronounced age-related lengthening of the supraglottic vocal tract.
      Alternatively, it is possible that elderly men systematically alter tongue
      position during vowel articulation while elderly women are less inclined to do
      so. Taken in conjunction with previous research, these findings suggest a "mixed
      model" of vocal tract resonance changes with aging in which an interaction exists
      between gender, the resonance effects of laryngeal lowering, and vowel
      articulatory patterns.

PMID- 11575630
TI  - Effects of microphone type on acoustic measures of voice.
AB  - Acoustic measures provide an objective means to describe pathological voices and
      are a routine component of the clinical voice examination. Because the voice
      sample is obtained using a microphone, microphone characteristics have the
      potential to influence the values of parameters obtained from a voice sample.
      This project examined how the choice of microphone affects key voice parameters
      and investigated how one might compensate for such microphone effects through
      filtering or by including additional parameters in the decision process. A
      database of 53 normal voice samples and 100 pathological voice samples was used
      in four experiments conducted in an anechoic chamber using four different
      microphones. One omnidirectional microphone and three cardioid microphones were
      used in these experiments. The original voice samples were presented to each
      microphone through a speaker located in an anechoic chamber, and the output of
      each microphone sampled to computer disk. Each microphone modified the frequency
      spectrum of the voice signal; this, in turn, affected the values of the voice
      parameters obtained. These microphone effects reduced the accuracy with which
      acoustic measures of voice could be used to discriminate pathological from normal
      voices. Discrimination performance improved when the microphone output was
      filtered to compensate for microphone frequency response. Performance also
      improved when spectral moment coefficient parameters were added to the vocal
      function parameters already in use.

PMID- 11575631
TI  - Comparison of singer's formant, speaker's ring, and LTA spectrum among classical
      singers and untrained normal speakers.
AB  - Many studies have described and analyzed the singer's formant. A similar
      phenomenon produced by trained speakers led some authors to examine the speaker's
      ring. If we consider these phenomena as resonance effects associated with vocal
      tract adjustments and training, can we hypothesize that trained singers can carry
      over their singing formant ability into speech, also obtaining a speaker's ring?
      Can we find similar differences for energy distribution in continuous speech?
      Forty classically trained singers and forty untrained normal speakers performed
      an all-voiced reading task and produced a sample of a sustained spoken vowel /a/.
      The singers were also requested to perform a sustained sung vowel /a/ at a
      comfortable pitch. The reading was analyzed by the long-term average spectrum
      (LTAS) method. The sustained vowels were analyzed through power spectrum
      analysis. The data suggest that singers show more energy concentration in the
      singer's formant/speaker's ring region in both sung and spoken vowels. The
      singers' spoken vowel energy in the speaker's ring area was found to be
      significantly larger than that of the untrained speakers. The LTAS showed similar
      findings suggesting that those differences also occur in continuous speech. This
      finding supports the value of further research on the effect of singing training
      on the resonance of the speaking voice.

PMID- 11575632
TI  - Objective voice quality analysis before and after onset of unilateral vocal fold
      paralysis.
AB  - This study was designed to investigate objective voice quality measurements in
      unilateral vocal fold paralysis (UVFP) by eliminating intersubject variability.
      To our knowledge this is the first report objectively analyzing paralytic
      dysphonia as compared to the same voice before onset of UVFP. The voices of two
      male subjects were prospectively recorded before and after the onset of
      iatrogenic UVFP (thoracic surgery). The following acoustic measurements of the
      vowel /a/ were performed using the CSL and MDVP (Kay Elemetrics): jitter,
      shimmer, harmonics-to-noise ratio, cepstral peak prominence, the relative energy
      levels of the first harmonic, the first formant and the third formant, the
      spectral slope in the low-frequency zone (0-1 kHz and 0-2 kHz), and the relative
      level of energy above 6 kHz. Distribution of spectral energy was analyzed from a
      long-term average spectrum of 40 seconds of text. Laryngeal aerodynamic
      measurements were obtained for one patient before and after onset of paralysis
      using the Aerophone II (Kay Elemetrics). Pitch and amplitude perturbation
      increased secondary to UVFP, while the harmonics-to-noise ratio and the cepstral
      peak prominence decreased. A relative increase in the mid-frequency and high
      frequency ranges and a decrease in the low-frequency spectral slope were
      observed. Mean airflow rate and intraoral pressure increased, and glottal
      resistance and vocal efficiency decreased secondary to UVFP. The findings of this
      self-paired study confirm some but not all the results of previous studies.
      Measures involving the fundamental and the formants did not corroborate previous
      findings. Further investigation with vocal tract modeling is warranted.

PMID- 11575633
TI  - Acoustic measures of symptoms in abductor spasmodic dysphonia.
AB  - Speech of patients with abductor spasmodic dysphonia (ABSD) was analyzed using
      acoustic analyses to determine: (1) which acoustic measures differed from
      controls and were independent factors representing patients' voice control
      difficulties, and (2) whether acoustic measures related to blinded perceptual
      counts of the symptom frequency in the same patients. Patients' voice onset time
      for voiceless consonants in speech were significantly longer than the controls (p
      = 0.015). A principle components analysis identified three factors that accounted
      for 95% of the variance: the first factor included sentence and word duration,
      frequency shifts, and aperiodic instances; the second was phonatory breaks; and
      the third was voice onset time. Significant relationships with perceptual counts
      of symptoms were found for the measures of acoustic disruptions in sentences and
      sentence duration. Finally, a multiple regression demonstrated that the acoustic
      measures related well with the perceptual counts (r2 = 0.84) with word duration
      most highly related and none of the other measures contributing once the effect
      of word duration was partialed out. The results indicate that some of the voice
      motor control deficits, namely aperiodicity, phonatory breaks, and frequency
      shifts, which occur in patients with ABSD, are similar to those previously found
      in adductor spasmodic dysphonia. Results also indicate that acoustic measures of
      intermittent disruptions in speech, voice onset time, and speech duration are
      closely related to the perception of symptom frequency in the disorder.

PMID- 11575634
TI  - Consistency of inhalatory breathing patterns in professional operatic singers.
AB  - Respiratory behavior is generally considered important to voice function, the
      assumption being that it affects the voice source. Accurate and consistent
      control of the voice source is particularly important in professional operatic
      singing. An erratic behavior of a factor influencing voice production is
      incompatible with a well-controlled vocal behavior. We analyzed the consistency
      of inhalatory breathing patterns during singing in five professional operatic
      singers, using the same material as in a previous investigation of phonatory
      breathing patterns. Rib cage (RC) and abdominal wall (AW) movements were recorded
      by respiratory inductive plethysmography. Consistency was analyzed in terms of
      the mean correlation between three takes of ten musical phrases. Results revealed
      a high consistency in lung volume (LV) change and RC movements in all singers and
      in AW movements in three singers. Consistency across different phrases was
      slightly lower. The results are compatible with the idea that inhalatory behavior
      is important to voice source in singing. A high correlation between LV change and
      RC movement was found in all singers and between LV change and AW movement in
      three. The contribution to LV change from RC was greater than that from AW in all
      singers.

PMID- 11575635
TI  - Effects of inhalatory abdominal wall movement on vertical laryngeal position
      during phonation.
AB  - The configuration of the body resulting from inhalatory behavior is sometimes
      considered a factor of relevance to voice production in singing and speaking
      pedagogy and in clinical voice therapy. The present investigation compares two
      different inhalatory behaviors: (1) with a "paradoxical" inward movement of the
      abdominal wall, and (2) with an expansion of the abdominal wall, both with regard
      to the effect on vertical laryngeal position during the subsequent phonation.
      Seventeen male and 17 female healthy, vocally untrained subjects participated. No
      instructions were given regarding movements of the rib cage. Inhaled air volume
      as measured by respiratory inductive plethysmography, was controlled to reach 70%
      inspiratory capacity. Vertical laryngeal position was recorded by two-channel
      electroglottography during the subsequent vowel production. A significant effect
      was found; the abdomen-out condition was associated with a higher laryngeal
      position than the abdomen-in condition. This result apparently contradicted a
      hypothesis that an expansion of the abdominal wall would allow the diaphragm to
      descend deeper in the torso, thereby increasing the tracheal pull, which would
      result in a lower laryngeal position. In a post-hoc experiment including 6 of the
      subjects, body posture was studied by digital video recordings, revealing that
      the two inhalatory modes were clearly associated with postural changes affecting
      laryngeal position. The "paradoxical" inward movement of the abdominal wall was
      associated with a recession of the chin toward the neck, such that the larynx
      appeared in a lower position in the neck, for reasons of a postural change. The
      results suggest that the laryngeal position can be affected by the inhalatory
      behavior if no attention is paid to posture, implying that instructions from
      clinicians and pedagogues regarding breathing behavior must be carefully
      formulated and adjusted in order to ensure that the intended goals are reached.

PMID- 11575636
TI  - Efficacy of a behaviorally based voice therapy protocol for vocal nodules.
AB  - The aim of this study was to assess the effects on vocal function of voice
      therapy for vocal nodules. Perceptual and physiological progressive changes were
      examined during a strictly structured, behaviorally based voice therapy protocol
      in which 11 women with vocal nodules participated. Randomized audio recordings
      from pretherapy and from each of the therapy approaches (vocal hygiene,
      respiration, direct facilitation, carryover) were used for perceptual
      evaluations. Six speech-language pathologists rated ten voice quality parameters.
      Two evaluation procedures were performed and compared. Interlistener reliability
      was sufficiently high in both tests. Significant effects of therapy were found
      for decreased overall dysphonia, press, instability, gratings, roughness, vocal
      fry, and "scrape." Nonsignificant group effects were found for breathiness,
      aphonic instances, and lack of sonority. No significant parameter changes
      occurred between baseline assessment and the completion of the initial (vocal
      hygiene) phase of therapy. Significant changes were found following the direct
      facilitation and respiration phases of therapy. Videostroboscopic evaluations
      made by two laryngologists showed that in no case were the nodules completely
      resolved. However, the nodules had decreased in size and edema was reduced after
      therapy for all clients, but one. Combined results suggest: (1) Alterations in
      vocal function were reflected in perceptual parameters, and (2) the voice therapy
      had a positive effect on voice quality, vocal status, and vocal function for the
      majority of the vocal nodule clients.

PMID- 11575637
TI  - The prevalence of voice disorders among day care center teachers compared with
      nurses: a questionnaire and clinical study.
AB  - The acceptance of voice disorders by day care center teachers as an occupational
      disease is not an invariably established practice. This is due to the lack of
      reliable evidence of a higher risk for voice disorders in this profession. To
      find out the risk of voice disorders, an epidemiological study was conducted
      among day care center teachers (n = 262), using hospital nurses (n = 108) as a
      control group. Symptoms were charted by a questionnaire. In a clinical
      examination made by a laryngologist, the voice quality was assessed and the
      laryngeal status noted. Teachers at day care centers had significantly more voice
      disorders than did nurses. Vocal nodules and laryngitis findings appeared
      significantly more frequently among day care center teachers than among those in
      the control group. The results prove voice disorders to be more frequent among
      day care center teachers than among control group subjects, and also that the
      main cause for this may be a higher vocal loading among day care center teachers
      than among control group subjects.

PMID- 11575638
TI  - Shifts in relative prevalence of laryngeal pathology in a treatment-seeking
      population.
AB  - The prevalence of laryngeal pathology in a treatment-seeking population of
      southwestern Ohio underwent a 15-year reexamination. Relationships between
      pathology and demographic variables of age, gender, and occupation were
      investigated. Data were collected from 1,158 new patients seen by participating
      otolaryngologists between 1996 and 1998. The most frequent pathologies were
      reflux laryngitis, functional (including diagnoses of laryngeal myasthenia and
      hoarseness), vocal fold paralysis, nodules, and laryngitis. Pathologies were
      found to occur more often in females, with some pathologies more common to one
      gender. Pathologies occurred more often in the older age categories. The most
      common occupations found in the sample were retired persons, executives/managers,
      and homemakers. Comparisons were made to an earlier investigation of laryngeal
      pathology in the same otolaryngology practices. Differences from the previous
      study were noted in the prevalence of pathology and the distribution of
      demographic variables. Relationships between pathology and demographic variables
      reported by the two studies were examined for consistency.

PMID- 11575639
TI  - Bamboo node: primary vocal fold lesion as evidence of autoimmune disease.
AB  - Descriptions of vocal fold lesions related to autoimmune diseases are rare in the
      literature, and focus mainly on rheumatoid nodules. This is the first report in
      which autoimmune diseases were promptly suspected by the observation of a unique
      white transverse submucosal lesion in the vocal fold during clinical examination.
      This lesion, reported only in autoimmune disease, has been called the bamboo node
      and its features are different from those of rheumatoid nodules. We report here
      on two patients who did not have a diagnosis of systemic disease before
      investigation of their main complaint of hoarseness. At the patients' first
      visit, vocal fold bamboo nodes were seen in the vocal fold and the
      otolaryngologist suspected the presence of an autoimmune disease. We requested
      clinical investigation to clarify our suspicion that there was an underlying
      systemic disease. After the investigation, both patients were shown to have
      autoimmune disease, Sjogren's syndrome and systemic lupus erythematous,
      respectively. This paper emphasizes the important role of the otolaryngologist in
      the detection of these unique lesions in the vocal folds through the conventional
      laryngeal methods. These methods consisted of direct observation with a rigid
      laryngeal endoscope and investigation of the patient's distinctive vibratory
      pattern by means of laryngeal stroboscopy. The method of treatment we used to
      obtain the best outcome in terms of voice improvement is also discussed.

PMID- 11575640
TI  - Vocal fold mucosal tears: maintaining a high clinical index of suspicion.
AB  - Vocal fold mucosal tears have been discussed in the literature rarely, although
      they are not uncommon clinically. Disruptions in the epithelium usually follow
      trauma that may result from voice abuse and/or misuse, coughing, and other
      causes. A high index of suspicion is necessary to avoid missing vocal fold
      mucosal tears, and strobovideolaryngoscopy is indispensable in making the
      diagnosis. A brief period of complete voice rest is the standard of care and
      appears to be helpful in avoiding adverse sequelae and advancing the healing
      process, but there are no scientific studies to confirm its efficacy. Mucosal
      tears may heal completely or may be followed by the development of vocal fold
      masses, scar, and permanent dysphonia.

PMID- 11575641
TI  - Diagnostic accuracy of fine needle aspiration cytology of the thyroid: impact of
      ultrasonography and ultrasonographically guided aspiration.
AB  - OBJECTIVE: To determine the impact of ultrasonography on the diagnostic accuracy
      of fine needle aspiration cytology (FNAC) of the thyroid. STUDY DESIGN: We
      compared two FNAC series. In period 1 we used neither ultrasonograph nor
      ultrasonographically-guided FNAC in the evaluation of thyroid nodules, while both
      tools were routinely applied in period 2. Moreover, in the former period all
      cellular follicular lesions were encountered among suspicious findings, while in
      period 2 we advised regular follow-up examinations instead of immediate surgery
      for patients with no significant atypia. The basis of follow-up examinations was
      ultrasonographic volumetry of the nodule and repeat FNAC on growing nodules.
      RESULTS: The number of FNAC, positive predictive value of FNAC, number of
      malignancies, sensitivity, the specificity and diagnostic accuracy were higher in
      period 2 as compared with period 1: 3,446 vs. 1,448; 45% vs. 16%, 39 vs. 29, 92%
      vs. 76%, 65% vs. 87% and 66% vs. 87%, respectively. CONCLUSION: The introduction
      of ultrasonography permits higher diagnostic accuracy of the evaluation process.
      This is achieved not only by lessening false negative reports but, more
      important, by decreasing false positive results.

PMID- 11575642
TI  - Aylesbury and cervitula spatulas: a comparative study to assess the adequacy of
      cervical smears.
AB  - OBJECTIVE: To assess whether the Aylesbury (Pharmaceutical Enterprises Ltd.,
      Pinelands, Capetown, South Africa) or Cervitula spatula (Harwill Medical,
      Capetown, South Africa) is more effective for adequate cervical smears in
      obstetric and gynecology patients. STUDY DESIGN: The Cervitula spatula was
      compared with the Aylesbury spatula by taking a total of 160 smears, which were
      examined cytologically. This consisted of 40 obstetric and 40 gynecology
      patients. The sequence in which the spatiulas were used was determined by
      computer randomization. Our main outcome criterion was whether both ectocervical
      and endocervical cells were present, thus making the smear adequate. Our numbers
      were too small to draw conclusions on the cytologic abnormalities detected
      between the two spatulas. RESULTS: The Cervitula was more effective for the
      identification of endocervical cells in obstetric patients (P = .0008). When
      combining the obstetric and gynecology groups, the Cervitula was also better in
      obtaining endocervical cells, but this did not reach statistical significance (P
      = .016). CONCLUSION: Pap smear sampling with the Cervitula reduces the number of
      cases without endocervical cells, which would constitute an inadequate smear,
      requiring unnecessary recall of patients for repeat smears.

PMID- 11575643
TI  - Summer spores of birch rust fungus in Papanicolaou smears from healthy mass
      screening participants.
AB  - OBJECTIVE: To evaluate the origin and identification of mysterious particles in
      Papanicolaou smears from healthy, asymptomatic women participating in a local
      mass screening program. STUDY DESIGN: The material consisted of 16,000
      cerricovaginal smears studied at the cytology laboratory of Pathology Laboratory
      of South-Western Finland Ltd. Unidentified particles were found in four
      apparently independent smears. All the slides were rescreened, but no further
      positive cases were found. RESULTS: Several swab samples were collected from the
      investigation room, but all were negative. Attempts at identification included
      numerous consultations. A telepathology consultation with the Cellular Division,
      Armed Forces Institute of Pathology, Washington, D.C., U.S.A., was conducted.
      Another teleconsultation with the reference laboratoryfor intestinal parasites in
      Iceland was conducted. Finally, the Aerobiology Unit, University of Turku, was
      consulted. The aerobiologist suggested that the particles were most probably
      summer spores of birch rust fungus (Melampsoridium betulinum). To confirm this we
      obtained a reference specimen of the fungus from the herbarium at the University
      of Turku. The morphology of the spore particles was identical to that in the
      cervicovaginal smears, proving that the smears were contaminated with birch rust
      fungus spores. CONCLUSION: Birch rust is ubiqutitous in Finland. Outside the
      hospital window there is a wide lawn behind which, at a distance of 70 m, there
      is a forest of birch trees. It is most likely that the rust spores flew in
      through the open window, to settle down on the surface of material that was used
      in sample taking. Airborne dust may cause misleading and surprising artefacts.
      Protection of specimens and instruments against dust should minimize the problem.

PMID- 11575644
TI  - Establishment and characterization of a cell line, MT-213-VGH, isolated from a
      mixed mullerian tumor of the uterus.
AB  - OBJECTIVE: To establish a cell line from a woman with malignant mixed mullerian
      tumor of the uterus and to examine the biologic properties of this cell line (MT
      213-VGH). STUDY DESIGN: Cells were cloned by the limiting dilution method.
      Histologic staining of mixed mullerian (mesodermal) tumor (MMMT) cells was
      performed with May-Grunwald-Giemsa and hematoxylin and eosin stain. After more
      than 20 passages, cells were used to estimate the population-doubling time and
      colony-forming efficiency of MMMT cells. The cell line exhibited considerable
      variation in the degree of sensitivity to diverse chemotherapy drugs in vitro.
      RESULTS: MMMT cells containing antigens for vimentin and myoglobin were detected,
      but those for CA-125, carcinoembryonic antigen, cytoskeleton, desmin, epithelial
      membrane antigen and fibronectin were not found. In addition, MT-213-VGH cells
      contained a mucinous substance; its chromosome model number is 45. This cell line
      showed differential sensitivities to chemotherapeutic agents, such as bleomycin,
      cisplatin, 5-fluorouracil and vinblastine. CONCLUSION: The establishment and
      availability of the number cell line MT-213-VGH for a malignant mixed mullerian
      tumor of the uterus should assist in research on new methods of managing this
      type of gynecologic cancer.

PMID- 11575645
TI  - Identification of a high-risk subgroup in cytology-positive stage IIIA
      endometrial cancer.
AB  - OBJECTIVE: To identify a high-risk subgroup among patients with cytology-positive
      stage IIIA endometrial cancer. STUDY DESIGN: Fifty-four stage IIIA endometrial
      cancer patients who were positive only on peritoneal cytology were divided into
      two groups based on the cytologic pattern of their peritoneal smears. In group A,
      malignant cell clusters had well-defined edges, while the tumor cell clusters had
      scalloped edges in group B. The prognostic significance of these findings was
      investigated. RESULTS: The five-year disease-free survival rate was 97.5% in
      group A (n=40) versus 50% in group B (n = 14). Multivariate analysis confirmed
      that the cytologic pattern had an independent influence on survival. CONCLUSION:
      Positive peritoneal cytology composed of malignant cell clusters with well
      defined edges has no impact on survival. Only endometrial cancer patients who
      show tumor cell clusters with scalloped edges in peritoneal smears are worth
      considering for upstaging.

PMID- 11575646
TI  - Interobserver and intraobserver variability in the cytologic diagnosis of normal
      and abnormal metaplastic squamous cells in pap smears.
AB  - OBJECTIVE: Interoberver variability has important implications for patient care,
      diagnostic error and medical litigation. In the management of any cervical
      epithelial abnormality, its biologic significance as well as diagnostic
      reproducibility is very important. Interobserver variability has not been
      measured adequately for metaplastic squamous lesions. We analyzed interobserver
      and intraobserver variability and diagnostic accuracy in the diagnosis of
      dysplastic metaplastic cells. STUDY DESIGN: Sixty Pap smears from patients with
      abnormalities of metaplastic squamous cells of varying severity were selected
      from the files of Lankenau Hospital, Wynnewood, Pennsylvania, U.S.A., diagnosed
      between 1990 and 1996. These were reviewed by four observers with different
      levels of cytology experience. Each of the observers blindly and independently
      reviewed all Pap smears. Tabulated results were analyzed to determine
      interobserver and intraobserver variability and diagnostic accuracy. RESULTS:
      Statistically significant interobserver reproducibility was found between both
      inexperienced observers as well as between observers 1 (experienced) and 3
      (inexperienced) and between observers 2 (experienced) and 4 (inexperienced). The
      observed degree of agreement between both experienced observers (1 and 2)
      reflected random rating rather than reproducibility. There was no difference in
      interobserver reproducibility in low vs. high grade lesions. Intraobserver
      reproducibility had no significant correlation with experience of the observer.
      The sensitivity ranged from 0.69 to 0.97 (mean, 0.79), while the specificity
      ranged from 0.09 to 0.46 (mean, 0.30). Mean diagnostic accuracy was better in
      benign and low grade squamous intraepithelial lesions in comparison to high grade
      squamous intraepithelial lesions. CONCLUSION: There was good interobserver
      agreement in classifying squamous metaplastic lesions. The agreement did not
      correlate with grade of dysplasia or experience of the cytopathologists. These
      findings should be considered in making treatment, quality assurance and legal
      decisions. A larger study is indicated to study interobserver and intraobserver
      variability and define cytologic criteria for lesions of metaplastic squamous
      cells.

PMID- 11575647
TI  - Performance of the AutoPap Primary Screening System in the detection of high-risk
      cases in cervicovaginal smears.
AB  - OBJECTIVE: To assess the performance of the AutoPap Primary Screening System
      (APSS) (TriPath Imaging, Inc., Burlington, North Carolina, U.S.A.) for the
      detection of high grade cervical squamous intraepithelial lesions and invasive
      cervical cancer. STUDY DESIGN: A total of 14,779 consecutive conventional Pap
      smears were processed by the APSS. All slides designated as "Review" by the
      device were manually screened according to the Bethesda System. The ranking
      scores obtained from the device were compared with the cytologic interpretations
      in all cases and with the final histologic diagnoses in the cases with cytologic
      severe abnormalities. RESULTS: The device classified 10,349 slides as Review
      (78%) and 2,912 (22%) as "No Further Review." In the 78% Review cases, the
      samples were ranked in descending order of potential abnormality, broken into
      quintiles. The correlation between the slide quintile ranks and the manual
      cytologic diagnosis indicated that 90% of abnormal smears were categorized by the
      device as in the first and second quintile rank, and the correlation between the
      rank report of the device and the histologic diagnosis showed that all cases of
      HSIL or invasive carcinoma were in the top two ranks. No significant
      abnormalities were observed in any of the smears categorized as No Further
      Review. CONCLUSION: This study confirmed the effectiveness of APSS for the
      detection of Pap smears with severe abnormalities.

PMID- 11575648
TI  - Does liquid-based technology really improve detection of cervical neoplasia? A
      prospective, randomized trial comparing the ThinPrep Pap Test with the
      conventional Pap Test, including follow-up of HSIL cases.
AB  - OBJECTIVE: To compare the sensitivity, specificity and specimen adequacy of the
      ThinPrep Pap Test (TP) with the conventional Pap Test (CV) in a low-risk
      population with subsequent follow-up of HSIL cases. STUDY DESIGN: A prospective,
      randomized, controlled design was chosen to compare the TP with CV. Cytologic
      diagnosis and specimen adequacy were evaluated and compared with histology data
      in high grade squamous intraepithelial lesion (HSIL) cases. Fifteen gynecologists
      in private practice, all trained in colposcopy, participated in the trial.
      Cytologic diagnosis, specimen adequacy and follow-up of the cytologic HSIL cases
      were compared in the two groups. In total, 1,999 patients were included, 997 in
      the TP group and 1,002 in the CV group. Randomization assignments were designated
      on cytology case report forms, which were placed in sealed envelopes. Each
      envelope had a sequential randomization number on the outside to allow tracking
      and authentication of randomization assignments. RESULTS: Comparison of results
      between CVs and TPs revealed no statistically significant differences in all
      diagnostic categories, ranging from "within normal limits" to HSIL. Specimen
      adequacy, however, was superior with CVs (P < .001). The cytologic diagnosis of
      HSIL correlated with the histologic diagnosis in 91% of the TP group and 100% of
      the CV group. CONCLUSION: Because there was no statistically significant
      difference in sensitivity and specificity of the two techniques, improved
      detection of cervical abnormalities and better specimen adequacy might not be a
      consequence of utilizing liquid-based preparations but of a better sampling
      technique. Removing mucus and cellular debris from the cervical surface with a
      cellulose swab before sampling cells with a proper sampling device results in the
      same sensitivity and specimen adequacy and is much less expensive than the liquid
      based technique.

PMID- 11575649
TI  - Aspiration cytology in the diagnosis of primary tumors of skin adnexa.
AB  - OBJECTIVE: To evaluate the cytologic features and pitfalls in the cytodiagnosis
      of certain tumors of skin adnexa. STUDY DESIGN: Smears from five nodular basal
      cell carcinomas, two chondroid syringomas and one case each of primary mucinous
      carcinoma, Merkel cell tumor, trichoepithelioma, pilomatrixoma and eccrine
      spiradenocarcinoma, all histologically confirmed, were evaluated with special
      attention to cytologic features that may aid the diagnoses. RESULTS: Ten of 12
      (83.3%) adnexal tumors were correctly recognized on aspiration cytology. The five
      basal cell carcinomas were atypical in presentation and clinically unsuspected
      but were diagnosed on cytology. The chondroid syringomas and Merkel cell tumor
      could also be diagnosed due to awareness of the cytologic features and sound
      clinical correlation. The eccrine spiradenocarcinoma was diagnosed as spiradenoma
      because of improper assessment of local invasion and incorrect mitotic count in
      the aspirates. The diagnosis was inaccurate in primary mucinous carcinoma as the
      aspirate yielded mainly mucin. CONCLUSION: Although exact subtyping of tumors of
      skin adnexa may not always be essential, certain benign adnexal tumors have
      aggressive counterparts (e.g., eccrine spiradenomas), while others clinically
      mimic metastases or small round cell carcinomas (e.g., Merkel cell tumors). Thus,
      correct cytodiagnoses and awareness of the limitations of cytology (such as in
      the assessment of local invasion) in these instances help to outline surgical
      management.

PMID- 11575650
TI  - Fine needle aspiration cytologic findings of breast mucinous neoplasms:
      differential diagnosis between mucocelelike tumor and mucinous carcinoma.
AB  - OBJECTIVE: To report the cytologic findings of mucocelelike tumor and mucinous
      carcinoma. STUDY DESIGN: All mucinous neoplasms diagnosed by fine needle
      aspiration and confirmed by histologic examination were reviewed to detect the
      cytologic findings helpful for the differentiation. The cytologic findings were
      correlated with the histologic findings. RESULTS: Cytologically, mucinous
      carcinomas were highly cellular and showed many single epithelial cells and
      variably formed epithelial cell clusters in abundant extracellular mucin.
      Malignant cells exhibited round, atypical nuclei; granular chromatin; and small
      nucleoli. Mucocele like tumor showed low cellularity with scanty, monolayered,
      small sheets of epithelial cells and abundant, extracellular mucin. Myoepithelial
      cells were present within the epithelial cell sheets. Tumor cells were usually
      small, with uniform, round nuclei; fine chromatin; and absence of nucleoli.
      CONCLUSION: Cytologic findings of mucocelelike tumor and mucinous carcinoma were
      different in cellularity, shape of cell clusters and nuclear features, although
      mucocelelike tumors having a carcinoma component were similar to mucinous
      carcinoma. Awareness of the cytologic findings of breast mucinous neoplasms is
      important to make a specific diagnosis.

PMID- 11575651
TI  - Presence of endocervical cells and number of slides in cervicovaginal smears:
      differences in performance between gynecologists.
AB  - OBJECTIVE: To study the association of precancerous cervical lesions with the
      presence of endocervical cells on Pap smears; and to evaluate gynecologists'
      approaches to the information on smear reports regarding endocervical cell
      status. STUDY DESIGN: Pap smear reports on 1,637 samples sent by 12 gynecologists
      were analyzed. The presence of endocervical cells, number of glass slides used
      per patient, and frequency and distribution of "atypia" and of pathogenetic
      microorganisms were recorded. Gynecologists' performances were compared, and
      their reactions to the reported lack of endocervical cells in their smears were
      evaluated. RESULTS: Atypia was detected significantly more frequently in samples
      with endocervical cells (1 in 664 versus 31 in 973, P < .01). Likelihood of
      detecting a pathogenetic microorganism, however, was not affected by the presence
      or absence of endocervical cells. In samples from certain gynecologists,
      endocervical cells were present most of the time, and in others they were
      generally lacking. This pattern did not change over time; specifically, the
      performance of the latter group of gynecologists did not improve in spite of
      their receiving information on the absence of endocervical cells in their
      samples. CONCLUSION: The performance of the "smear taker" is an important
      component of Pap smear screening practice. Efforts to increase the quality of
      service should cover not only laboratories but also gynecologists and others who
      take smears. Screening can only be successful as a system in the presence of good
      samples.

PMID- 11575652
TI  - Fine needle aspiration cytology diagnosis of renal medullary carcinoma: a case
      report.
AB  - BACKGROUND: Renal medullary carcinoma is a recently described, highly aggressive
      neoplasm that affects predominantly young African American males with a history
      of sickle cell trait. To the best of our knowledge, this is the first report of
      fine needle aspirate cytology (FNAC) findings of renal medullary carcinoma. CASE:
      A 14-year-old, African American male with a history of sickle cell trait
      presented with the sudden onset of third cranial nerve palsy. Radiographic
      examination demonstrated possible tumor masses in the brain, thorax and left
      kidney. Ultrasound-guided fine needle aspiration was performed on the left
      kidney, and a cytologic diagnosis of "suspect renal medullary carcinoma" was
      rendered. The cytologic diagnosis was confirmed by tissue examination.
      CONCLUSION: The cytologic features of renal medullary carcinoma include loosely
      cohesive clusters and single epithelioid cells with cytologic atypia, including
      high nuclear/cytoplasmic ratios, hyperchromasia, prominent nucleoli and
      cytoplasmic vacuolation. These cytologic findings, coupled with clinical findings
      (young black male with sickle cell trait), allow recognition of this rare renal
      neoplasm.

PMID- 11575653
TI  - Neuroblastoma with concomitant giardiasis: report of a case with diagnosis by
      fine needle aspiration cytology.
AB  - BACKGROUND: Diagnosis of two pathologies, including a neoplasm and infectious
      condition, by fine needle aspiration (FNA) cytology in the same patient is rare.
      CASE: A 2-year-old, male child presented with fever, abdominal pain and abdominal
      mass. Imaging findings were strongly in favor of a neuroblastoma. FNA smears from
      the mass revealed fecal material containing numerous trophozoites of Giardia
      lamblia. FNA was repeated in view of the imaging findings. Repeat smears showed a
      small round cell tumor with rosettes and background filamentous/fibrillar
      material consistent with a neuroblastoma. Chemotherapy reduced the mass
      considerably. Histopathology of the resected residual mass revealed a
      ganglioneuroma in addition to remnants of neuroblastoma. The patient was free of
      disease two years after the initiation of chemotherapy. CONCLUSION: When FNA
      cytology shows an infectious pathology in the clinical and imaging setting of a
      tumor, FNA should be repeated so that an important component of the diagnosis is
      not missed.

PMID- 11575654
TI  - Fine needle aspiration cytology of the malignant variant of ossifying fibromyxoid
      tumor of soft parts: a case report.
AB  - BACKGROUND: Ossifying fibromyxoid tumor (OFMT) of soft parts is a rare, recently
      defined, fibroosseous neoplasm, generally regarded as clinically benign; however,
      one-third of cases recur locally, and several malignant examples have been
      reported. Fine needle aspiration (FNA) cytology of the tumor is rarely described
      in the literature. We provide the first cytomorphologic study of the malignant
      variant. CASE: A 70-year-old man presented with an intramuscular mass in the
      right buttock. Computed tomography revealed ossification within the mass and
      multiple pulmonary nodules. FNA biopsy showed round and polygonal to spindled
      tumor cells, arrayed singly, cordlike or in small aggregates, with scattered
      dense stromal fragments and a slightly myxoid background. The nuclei showed
      significant pleomorphism accompanied by coarse chromatin with clumping, irregular
      contours, and one to two distinct nucleoli. The tumor cells were recognizable as
      sarcoma, with no evidence of high grade malignancy. The tumor was totally
      excised, histopathologically confirmed as the malignant variant of OFMT of soft
      parts, and immunohistochemically and ultrastracturally analyzed as of neural
      origin. CONCLUSION: The FNA specimen revealed that the cytomorphology was
      consistent with the histologic features of the malignant variant of OFMT, but
      several characteristic histologic parameters, such as multilobular proliferation
      and peripherally placed mature, bony trabeculae, were not reflected in the
      aspirates. Although FNA cytologic findings may be of limited diagnostic utility
      in OFMT, radiographic evidence of calcification/ossification suggests that OFMT
      should be subjected to differential diagnosis with fine needle aspiration biopsy
      of soft tissue tumors. Additional studies will be required for further
      clarification.

PMID- 11575655
TI  - Amelanotic malignant melanoma arising in an ovarian cystic teratoma: a case
      report.
AB  - BACKGROUND: Malignant melanoma arising in a cystic teratoma is extremely rare. We
      report the clinicopathologic and cytopathologic features of an amelanotic
      malignant melanoma arising in an ovarian cystic teratoma. CASE: A 55-year-old
      woman presented with an asymptomatic right ovarian mass, showing features of
      cystic teratoma according to preoperative computed tomography and magnetic
      resonance imaging. The resected teratoma was suspected to include a nonepithelial
      malignancy in a touch preparation from a solid component. The tumor showed
      immunoreactivity for Melan-A, S-100 and HMB-45 in the absence of melanin
      granules, which established the diagnosis of amelanotic malignant melanoma
      arising in an ovarian cystic teratoma. CONCLUSION: Cytopathologic findings from
      touch preparations and immunohistochemical staining are useful for the diagnosis
      of amelanotic malignant melanoma arising in an ovarian cystic teratoma.

PMID- 11575657
TI  - Fine needle aspiration cytology of sclerosing lobular hyperplasia of the breast:
      a case report.
AB  - BACKGROUND: Sclerosing lobular hyperplasia presenting as a palpable,
      circumscribed nodular mass in a young female's breast is characterized
      histologically by prominent hyperplasia of the lobules and sclerosis of the
      intralobular connective tissue. The cytomorphologic features and differential
      diagnosis of the lesion are presented. CASE: A 14-year-old female presented with
      a painless, progressively increasing, nodular, firm, mobile lump measuring 5 x 5
      cm in the right breast. The clinical and radiologic diagnosis was fibroadenoma.
      Fine needle aspiration smears showed a clean background with uniform, round to
      oval epithelial cells in flat sheets, round clusters and rosettelike (acinar)
      arrangements. A few naked nuclei were present, while stromal fragments were not
      seen. CONCLUSION: When analyzed in the context of the clinical findings, the
      cytologic features of sclerosing lobular hyperplasia help to differentiate it
      from other benign palpable nodular lesions of the juvenile breast.

PMID- 11575656
TI  - Fine needle aspiration biopsy of anaplastic thyroid carcinoma developing from a
      Hurthle cell tumor: a case report.
AB  - BACKGROUND: Anaplastic thyroid carcinoma is a highly malignant tumor in elderly
      people with a long history of multinodular goiter and is usually associated with
      a rapidly fatal clinical evolution. The tumor often develops as a result of
      anaplastic transformation of a slowly growing papillary carcinoma or follicular
      neoplasm. CASE: An 85-year-old woman had a multinodular goiter and had been
      asymptomatic, with a normal white blood cell count and chest radiograph three
      months prior to her hospital admission for the treatment. The tumor presented
      with low grade fever, leukocytosis, multiple metastatic lung nodules and
      enlargement of the intrathoracic thyroid in a period of three months, causing
      compression of the esophagus and trachea. Despite a total thyroidectomy, the
      tumor recurred within one month and caused dysphagia and death. CONCLUSION: FNAB
      permitted the diagnosis of an anaplastic thyroid carcinoma arising from an
      intrathoracic Hurthle cell tumor.

PMID- 11575658
TI  - Fine needle aspiration cytology of metastatic hepatic adrenocortical carcinoma
      mimicking hepatocellular carcinoma: a case report.
AB  - BACKGROUND: Adrenocortical carcinoma (AC) is a rare neoplasm, usually considered
      one of the most morbid and lethal human tumors. It occurs primarily in children
      and young adults and often presents with advanced and/or metastatic disease.
      CASE: A 9-year-old boy with a previous diagnosis of adrenocortical carcinoma
      underwent computed tomography (CT)-guided fine needle aspiration (FNA) for
      preoperative investigation of a hepatic mass. All smears revealed abundant groups
      of cells surrounding an interconnective, thin-walled, central vascular core.
      These cells showed finely vacuolated, large cytoplasm with eccentrically placed
      nuclei. Occasionally, cells underwent a sudden, marked increase in size, with
      prominent atypia. Multinucleated, atypical giant cells and high mitotic rate were
      also evident. The cytologic findings resembled the previous histologic
      adrenocortical carcinoma features. CONCLUSION: The cytologic features of
      metastatic hepatic adrenocortical carcinoma may mimic those of hepatocellular
      carcinoma. However, the presence of atypical multinucleated and pleomorphic cells
      with microvacuolated cytoplasm and eccentric nuclei as well as the absence of
      naked nuclei and endothelial linings yield the diagnosis of adrenocortical
      carcinoma. Nevertheless, other space-occupying liver lesions in children must
      also be considered. This case demonstrates the usefulness of CT-localized FNA
      biopsy in hepatic masses in children, and discusses the possible cytologic
      differential diagnosis.

PMID- 11575659
TI  - Voided urine cytology of papillary renal cell carcinoma and renal calculus:
      report of a case with emphasis on the importance of cytologic screening in high
      risk individuals.
AB  - BACKGROUND: Preoperative diagnosis of cases of renal calculus complicated with
      papillary renal cell carcinoma (RCC) by image analysis is usually difficult.
      CASE: A 50-year-old man who had a past history of renal calculus suffered from
      macrohematuria and abdominal pain for one month was admitted to our hospital.
      Ultrasonographic examination revealed a 4-cm tumor shadow in the right kidney; it
      was hypovascular in arteriography. Papillary cell clusters with abundant
      cytoplasm were found by the cytologic examination of voided urine. Their nuclei
      were oval and situated eccentrically in the cytoplasm. The nuclear/cytoplasmic
      ratio was increased. Fine, granular chromatin was distributed evenly, and the
      nuclear membrane was thin and nearly smooth. Several small nucleoli were evident.
      All these findings were indicative of a diagnosis of papillary RCC. Histology of
      nephrectomy specimens confirmed the diagnosis. CONCLUSION: Voided urine cytology
      can be useful for screening and follow-up of patients with papillary RCC.

PMID- 11575660
TI  - Basal cell adenocarcinoma of the salivary gland: report of a case with morphology
      on fine needle aspiration cytology.
AB  - BACKGROUND: Basal cell adenocarcinoma of the parotid is rare and prone to recur.
      CASE: A 54-year-old woman had a history of afacial mass 12 years earlier that had
      been excised and was diagnosed as low grade adenocarcinoma of the parotid. Over
      the years, the patient had multiple local and lymph node recurrences. Histology
      of the excised local recurrent tumor showed basal cell adenocarcinoma, and FNAC
      of a separate recurrent nodule was performed. The aspirate showed moderate
      cellularity of basaloid cells with mildly pleomorphic nuclei, small nucleoli and
      occasional mitotic figures. The cells were mostly single, but some formed
      clusters with a rosettelike pattern of tumor cells surrounding central
      eosinophilic globules. A second, less prominent population of smaller cells with
      dark-staining nuclei was also noted. The differential diagnosis included adenoid
      cystic carcinoma, polymorphous low grade adenocarcinoma, and basal cell and
      pleomorphic adenoma. CONCLUSION: The cytologic features of basal cell
      adenocarcinoma are not distinctive, but the presence of two cell populations with
      moderate pleomorphism and a rosettelike pattern with central, eosinophilic
      globules may assist with its differentiation from other salivary gland neoplasms.

PMID- 11575661
TI  - Fine needle aspiration cytology of mucinous cystadenocarcinoma of the lung:
      report of a case with radiographic and histologic correlation.
AB  - BACKGROUND: Mucinous cystadenocarcinoma of the lung is an uncommon tumor. Because
      it contains relatively few neoplastic cells relative to the amount of mucin
      produced, diagnosis of this entity, particularly on small specimens, is
      exceedingly difficult. CASE: The diagnosis of adenocarcinoma was made on
      transthoracic fine needle aspiration from a patient with a right upper lobe lung
      mass. Abundant mucoid material suggested a mucin-producing neoplasm.
      Histopathology revealed a mucinous cystadenocarcinoma with focal mucinous
      bronchoalveolar carcinoma. CONCLUSION: The presence of copious extracellular
      mucin in fine needle aspirates from the lung otherwise diagnostic of
      adenocarcinoma should raise the possibility of a mucinous tumor. In particular,
      the diagnosis of mucinous cystadenocarcinoma may be suggested in cases that have
      a cystic appearance on imaging studies.

PMID- 11575662
TI  - Cytodiagnosis of hydatid disease presenting with Horner's syndrome: a case
      report.
AB  - BACKGROUND: The diagnosis of echinococcosis is based on clinical, radiologic and
      serologic findings. Fine needle aspiration (FNA) is useful in evaluating the
      lesion when the presentation is atypical. We report a case of hydatid cyst at the
      lung apex in which the diagnosis was made on FNA, with no adverse reaction to the
      aspiration. CASE: A 30-year-old male, a chronic smoker, presented with pain
      radiating to the medial two fingers of the right hand for two years. He also had
      miosis and ptosis of the right eye and anhidrosis of the right side of theface.
      There was wasting of small muscles in the right hand. Magnetic resonance imaging
      revealed a hyperintense mass at the apex of the right lung, thoracic inlet and
      adjacent vertebral bodies. A clinical diagnosis of Horner's syndrome due to
      pancoast tumor was rendered. Ultrasound-guided FNA showed protoscolices,
      scattered hooklets and bits of acellular laminated membrane, characteristic of
      echinococcosis. Surgical excision of the cyst was done. Gross and histopathologic
      examination of the excised cyst confirmed the diagnosis. CONCLUSION: FNA, though
      traditionally contraindicated, is a highly desirable, rapid, noninvasive
      diagnostic mode for echinococcosis. In view of its pathognomonic cytomorphologic
      features and numerous reports on cytodiagnosis in the literature, it is time to
      evaluate the diagnostic benefits and weigh the risks against the advantages of
      the technique.

PMID- 11575663
TI  - Mucinous adenocarcinoma of the ovary metastatic to the eye: report of a case with
      diagnosis by fine needle aspiration biopsy.
AB  - BACKGROUND: Metastatic malignancy involving the ocular uveal tract is rare.
      Approximately one-third of patients will present without a known primary site.
      This is the ninth reported clinically detected case of ovarian carcinoma
      metastatic to the eye, the second with mucinous differentiation and the first in
      which the diagnosis was established by fine needle aspiration (FNA). CASE: A
      woman developed ovarian mucinous adenocarcinoma metastatic to the choroid layer
      of the eye. CONCLUSION: FNA is useful in diagnosing lesions of the eye and orbit,
      including diagnosis of rare metastatic lesions.

PMID- 11575664
TI  - Nodular fasciitis of the breast: report of a case initially diagnosed by fine
      needle aspiration cytology.
AB  - BACKGROUND: Nodular fasciitis is a rare benign pseudosarcomatous proliferation of
      fibroblasts in the breast, in which the clinical examination and mammographic
      findings may closely mimic mammary carcinoma. CASE: A case of nodular fasciitis
      was diagnosed by fine needle aspiration. A 15-year-old girl was admitted to our
      hospital with a recently noticed, rapidly growing mass in the right breast. The
      aspirate contained cohesive groups of fusiform cells with elongated and oval
      nuclei, regular nuclear membranes and inconspicuous nucleoli, intermingled with
      scattered lymphocytes, red blood cells and characteristic granular background
      substance. A cytologic diagnosis of nodular fasciitis was made and confirmed
      histologically. CONCLUSION: Mammary nodular fasciitis is often clinically
      suspicious for carcinoma and rarely diagnosed by fine needle aspiration cytology.
      A literature search yielded only five reported cases. The cytologic diagnosis of
      this entity helps to choose the correct surgical procedure, preventing
      psychological trauma to the patient.

PMID- 11575665
TI  - Granulomatous inflammation of the breast in a pregnant woman: report of a case
      with fine needle aspiration diagnosis.
AB  - BACKGROUND: Granulomatous inflammation of the breast is an inflammatory process
      with multiple etiologies. It can accompany breast carcinoma or be idiopathic. It
      often presents clinically in a fashion mimicking carcinoma. Idiopathic
      granulomatous mastitis is strongly associated with lactation and is reported to
      occur in postpartum patients. This is the second fine needle aspiration (FNA)
      report of idiopathic granulomatous inflammation in the breast of a pregnant
      woman. CASE: A 27-year-old, 7-month-pregnant woman presented with a hard nodule
      in her right breast; on ultrasound examination it showed mixed echogenicity,
      suspicious for carcinoma. FNA showed granulomatous inflammation. The smears were
      highly cellular, with many clusters of and single epithelioid cells displaying
      moderate pleomorphism and prominent nucleoli in a background composed of
      neutrophils, plasma cells, lymphocytes and multinucleated cells. Core needle
      biopsy revealed a nonnecrotizing, granulomatous lesion. CONCLUSION: The diagnosis
      of granulomatous inflammation can be challenging, and the cytologic features can
      be difficult to separate from those of carcinoma. The relatively rare occurrence
      of this lesion and its cytologic features make it a potentially difficult
      diagnosis and diagnostic pitfall.

PMID- 11575666
TI  - Cytomorphologic features of nonspecific granulomatous mastitis diagnosed by
      imprint cytology.

PMID- 11575667
TI  - "Pick and smear" tissue concentration technique for bloody aspirates.

PMID- 11575668
TI  - Detecting chlamydia trachomatis infection in women.

PMID- 11575669
TI  - Cytology of cardiac angiosarcoma in fine needle aspirates.

PMID- 11575670
TI  - Seminal vesicle epithelium as a potential pitfall in the cytodiagnosis of
      presacral masses.

PMID- 11575671
TI  - Fine needle sampling cytology of palpable breast lesions with immediate
      reporting.

PMID- 11575672
TI  - Fine needle aspiration appearance of clear cell myoepithelioma of the salivary
      gland.

PMID- 11575673
TI  - Microfilaria in peritoneal fluid from an amicrofilaremic, pregnant woman.

PMID- 11575674
TI  - Vascular patterns as an aid to cytodiagnosis in fine needle aspiration.

PMID- 11575675
TI  - Cavitary lung mass representing primary pulmonary malignant lymphoma with initial
      diagnosis by fine needle aspiration biopsy.

PMID- 11575676
TI  - The "polka dot" cell.

PMID- 11575677
TI  - Fine needle aspiration biopsy of pancreatic endocrine neoplasms by endoscopic
      ultrasonographic guidance.

PMID- 11575678
TI  - The effects of dietary selenium on the immune system in healthy men.
AB  - Eleven men were fed foods naturally high or low in selenium for 120 d. Selenium
      intake was stabilized at 47 microg/d for 21 d, then changed to either 13 or 297
      microg/d for 99 d, leading to significantly different blood selenium and
      glutathione peroxidase concentrations. Serum immunoglobulins, complement
      components, and primary antibody responses to influenza vaccine were unchanged.
      Antibody titers against diphtheria vaccine were 2.5-fold greater after
      reinoculation in the high selenium group. White blood cell counts decreased in
      the high-selenium group and increased in the low-selenium group, resulting
      primarily from changes in granulocytes. Apparent increases in cytotoxic T
      lymphocytes and activated T-cells in the high-selenium group only approached
      statistical significance. Lymphocyte counts increased on d 45 in the high
      selenium group. In vitro proliferation of peripheral lymphocytes in autologous
      serum in response to pokeweed mitogen was stimulated in the high-selenium group
      by d 45 and remained elevated throughout the study, whereas proliferation in the
      low selenium group did not increase until d 100. This study indicates that the
      immune-enhancing properties of selenium in humans are the result, at least in
      part, of improved activation and proliferation of B-lymphocytes and perhaps
      enhanced T-cell function.

PMID- 11575679
TI  - Zinc and diabetes mellitus: is there a need of zinc supplementation in diabetes
      mellitus patients?
AB  - Diabetes mellitus is a group of metabolic disorders, the incidence of which
      varies widely throughout the world. The treatment of diabetes mellitus includes
      insulin, oral antidiabetic agents, and dietary regimens. Although the emphasis is
      on macronutrients intakes, there is strong evidence that there is an abnormal
      metabolism of several micronutrients in diabetic individuals. Zinc is one of the
      essential micronutrients of which status and metabolism is altered in this
      condition. This work is a short review about the close relation among zinc,
      glucose metabolism, and insulin physiology, as well as about the few experimental
      data about zinc absorption and zinc supplementation in diabetes mellitus
      patients.

PMID- 11575680
TI  - Influence of selenium on mercuric chloride cellular uptake and toxicity
      indicating protection: studies on cultured K-562 cells.
AB  - Selenium and mercuric chloride (MC) interactions regarding cellular uptake and
      selenium protection on MC toxicity have been studied. Human K-562 cells were
      pretreated or simultaneously treated with either selenite (5 or 50 microM) or
      selenomethionine (10 or 50 microM) together with MC (35 or 50 microM). Both
      treatments with selenite showed an increase of mercury uptake with increased
      selenium dose. In the pretreated or simultaneously treated selenite and 35 microM
      MC combinations, no inhibition of growth was seen, whereas all 50-microM MC
      combinations were toxic to the cells. A selenite-dependent protection was
      obtained for both exposure protocols when considering the cellular uptake of
      mercury. The cells died when the accumulation on d 4 reached more than about 0.8
      x 10(-15) mol/cell of mercury, whereas they survived up to twofold more mercury
      uptake when exposed to selenite. Selenomethionine gave, with a few exceptions,
      similar effects as selenite on MC uptake and toxicity.

PMID- 11575681
TI  - Relationship of blood trace elements to liver damage, nutritional status, and
      oxidative stress in chronic nonalcoholic liver disease.
AB  - Trace elements are involved in chronic liver diseases because these elements may
      have a direct hepatic toxicity or may be decreased as a consequence of the
      impaired liver function, particularly in patients with alcoholic cirrhosis and/or
      malnutrition. In this study, we determined plasma and erythrocytes trace elements
      in 50 inpatients with nonalcoholic chronic liver disease (11 with biopsy-proven
      chronic hepatitis, 39 with cirrhosis [16 in stage A according to Child-Pugh
      criteria, 23 Child B+C]), and in a control group of 10 healthy subjects by the
      proton induced x-ray emission method. The relationship between trace element
      concentration and the extent of liver damage, the nutritional status (by
      anthropometric evaluations), and various blood markers of oxidative stress-
      reduced glutathione, total lipoperoxides and malonyldialdehyde--was investigated.
      We found that cirrhotics had a significant decrease of Fe, Zn, Se, and GSH levels
      in the plasma and of GSH and Se in the erythrocytes with respect to the control
      and chronic hepatitis groups. GSH levels were related to the degree of liver
      damage; a significant direct correlation was observed among Se, Zn, and GSH
      plasma values and between GSH and Se in the erythrocytes. The trace element
      decrease was, on the contrary, independent of the degree of liver function
      impairment and only partially affected by the nutritional status. Data indicate
      that liver cirrhosis, even if not alcohol related, induces a decrease of Se and
      Zn and that, in these patients, an oxidative stress is present, as documented by
      the significant correlation between Se and GSH. The plasma Br level was higher in
      cirrhotics with respect to the control and chronic hepatitis groups.

PMID- 11575682
TI  - Assessment of fertility and infertility in boron-exposed Turkish subpopulations:
      3. Evaluation of fertility among sibs and in "borate families".
AB  - As a part of a work to reveal the health effects of boron and its compounds,
      fertility and infertility states of sibs of probands, contacted and interviewed
      in the field, and of their spouses were given. The purposes were to prevent
      duplications seemingly inevitable in a relatively small community with prevailing
      consanguinity while analyzing marriages over respective generations and to reveal
      if there occurred an aggregation of infertile couples. Any family without
      offspring after about the second year of marriage was considered primary
      infertile as adopted throughout the study and such families were ascertained
      through the individual pedigree charts set up according to the instructions of
      the proband, he (she) himself (herself) being excluded. The rates of childless
      families of this type were 0.0-3.4% among male and 0.9-3.8% among female sibs of
      the participant, and 2.3-10.0% among male and 0.0-5.6% among female sibs of his
      (her) spouse with averages of 2.3% of 1589, 2.6% of 1589, 4.0% of 1314, and 3.3%
      of 1436 instances, respectively. The differences were insignificant and the rates
      were not different from those concerning probands themselves and that of a
      comparable segment of the Turkish population. "Borate families/kindreds" with two
      or more members engaged in the borate industry were also assessed in order to
      detect if there was a significant clustering of infertiles within the kindred.
      Although it was difficult to compare with a matched group, few couples were
      examples of familial concentration of infertility. These results provided further
      support that boron exposure does not affect human reproduction primarily and most
      probably secondarily.

PMID- 11575683
TI  - Importance of storage conditions for the stability of zinc- and cadmium-induced
      metallothionein.
AB  - We examined the storage stability of metallothionein (MT), a cysteine-rich
      protein that has diagnostic potential as a cancer marker and in the assessment of
      Zn status and heavy-metal toxicity. MT was rapidly degraded in samples of rat
      whole liver at -20 degrees C or -70 degrees C. MT in supernatants from heat
      treated rat liver homogenates stored as 1:5 dilutions of liver from Zn- or Cd
      induced rats were stable (recovery >98%) for 100 d at temperatures of -70 degrees
      C and -196 degrees C but not at -20 degrees C, regardless of the presence of
      dithiothreitol (DTT) or argon. The variability of MT measurement by the 109Cd
      hemoglobin affinity assay was however greatest in samples from Zn-induced rats
      stored without DTT. The integrity of the MT protein in supernatants of heat
      treated homogenates stored for 100 d was demonstrated by Sephadex G-75
      chromatography. When heat-treated supernatants were stored as dilute solutions
      (1:125 of liver), MT was unstable regardless of treatment or storage temperature.
      Our findings show that liver MT is stable for at least 4 mo as a supernatant of a
      heat-treated homogenate (1:5 dilution of liver) when stored at or below -70
      degrees C and in the presence of DTT.

PMID- 11575684
TI  - Evaluation of the All Stars character education and problem behavior prevention
      program: effects on mediator and outcome variables for middle school students.
AB  - The effects of All Stars, a character education and problem behavior prevention
      program, on variables theorized to mediate problem behaviors and on the problem
      behavior variables of substance use, sexual behavior, and violence among middle
      school students are reported. In an independent, randomized, single-cohort,
      longitudinal evaluation of the program, 1,655 students completed pretest,
      posttest, and 1-year follow-up surveys measuring demographics, mediating
      variables, and behavioral outcome variables. Results indicate that the All Stars
      program, when administered by teachers, had an immediate effect on mediating
      variables that did not persist over time. Inclusion of ethnicity in the design
      showed that the program, when administered by specialists, had delayed effects on
      mediating variables for African American and Hispanic students. However, no
      consistent effects were found for student problem behaviors in either condition.
      Implications for prevention practice and directions for future research are
      discussed.

PMID- 11575685
TI  - The feasibility of a web-based surveillance system to collect health risk
      behavior data from college students.
AB  - This study examined the feasibility of collecting health risk behavior data from
      undergraduate students using a Web-based survey. Undergraduates were randomly
      selected and assigned randomly to a mail survey group and a Web survey group.
      There were no statistically significant differences between the two groups for
      demographics, response rates, item completion, and item completion errors. Yet
      differences were found for response time and sensitive item completion. This is
      the first study to demonstrate the feasibility of collecting health risk behavior
      data from undergraduates using the Web. Undergraduates are just as likely to
      respond to a Web survey compared with a mail survey and more likely to answer
      socially threatening items using this method. Also, the Web format and protocol
      required less time to administer. Researchers and practitioners conducting health
      survey research with college students or other homogeneous populations who have
      access to e-mail and the Web should consider using a Web-based survey design as
      an altemative to a mail, self-administered survey. In such a population, a Web
      based survey should not discourage participation, particularly if participants
      are interested in the questionnaire content.

PMID- 11575686
TI  - Photovoice ethics: perspectives from Flint Photovoice.
AB  - Photovoice is a participatory health promotion strategy in which people use
      cameras to document their health and work realities. As participants engage in a
      group process of critical reflection, they may advocate for change in their
      communities by using the power of their images and stories to communicate with
      policy makers. In public health initiatives from China to California, community
      people have used photovoice to carry out participatory needs assessment, conduct
      participatory evaluation, and reach policy makers to improve community health.
      This article begins to address ethical issues raised by the use of photovoice:
      the potential for invasion of privacy and how that may be prevented; issues in
      recruitment, representation, participation, and advocacy; and specific
      methodological techniques that should be used to minimize participants' risks and
      to maximize benefits. The authors describe lessons learned from the large-scale
      Flint Photovoice involving youth, adults, and policy makers.

PMID- 11575687
TI  - Factors related to cancer screening in Hispanics: a comparison of the perceptions
      of Hispanic community members, health care providers, and representatives of
      organizations that serve Hispanics.
AB  - Hispanics have lower rates of screening for cervical, breast, and colon cancer
      than non-Hispanics. Activities to increase cancer screening in this population
      may not be informed by Hispanics, which may have implications for success rates
      of interventions. In this study, the perceptions about cancer screening behaviors
      in Hispanics are compared among three groups: a random sample of respondents (75%
      Hispanic) to a population-based survey, health care providers (primarily non
      Hispanic), and representatives of organizations that serve Hispanics (36%
      Hispanic). While there was agreement that socioeconomic factors were important
      for cancer screening, differing views were expressed regarding the importance of
      cultural factors for cancer screening among Hispanics. Interventions developed by
      those who serve the Hispanic population may be based on inaccurate perceptions
      about the beliefs and practices of the population served. For effective
      interventions, it will be necessary to understand the factors important to
      Hispanics for cancer screening.

PMID- 11575688
TI  - Using theory to understand the multiple determinants of low participation in
      worksite health promotion programs.
AB  - Low participation at the employee or worksite level limits the potential public
      health impact of worksite-based interventions. Ecological models suggest that
      multiple levels of influence operate to determine participation patterns in
      worksite health promotion programs. Most investigations into the determinants of
      low participation study the intrapersonal, interpersonal, and institutional
      influences on employee participation. Community- and policy-level influences have
      not received attention, nor has consideration been given to worksite-level
      participation issues. The purpose of this article is to discuss one macrosocial
      theoretical perspective--political economy of health--that may guide
      practitioners and researchers interested in addressing the community- and policy
      level determinants of participation in worksite health promotion programs. The
      authors argue that using theory to investigate the full spectrum of determinants
      offers a more complete range of intervention and research options for maximizing
      employee and worksite levels of participation.

PMID- 11575689
TI  - Health risk behavior of rural secondary school students in Zimbabwe.
AB  - A socioculturally appropriate health risk behavior instrument, modeled after the
      U.S. Centers for Disease Control and Prevention's Youth Risk Behavior Survey
      (YRBS), was administered to 717 secondary school students in a rural area of
      Zimbabwe. Comparisons of risk behaviors by gender and school grade were made
      using univariate procedures and multiple logistic regression. Males were
      significantly more likely than females to have had sexual intercourse (odds ratio
      = 5.02, p < .0001) and to report drug use behaviors. Males also were
      significantly more likely to report early initiation (by age 13 years) of alcohol
      use, cigarette smoking, and marijuana use. School site violence and drug use
      behaviors also were prevalent in this sample. An interaction between gender and
      grade was evident for some behaviors. Additional research may further the
      understanding of these risk behaviors and facilitate development of effective,
      culturally relevant risk reduction programs.

PMID- 11575690
TI  - When is sex safe? Insiders' views on sexually transmitted disease prevention and
      treatment.
AB  - STD prevention programs promote practices and messages that are presumed to fit
      with most conditions of U.S. communities. Yet, the social and cultural contexts
      for low-income ethnic communities may frame STD prevention differently, so that
      people calculate their risk and take actions based on what they have learned
      through their own observations and life experiences. To understand how people at
      high risk for STDs make decisions and take actions to protect themselves from
      these diseases, the authors conducted 38 ethnographic interviews with individuals
      living in arural community in the South. Practices they reported include
      selecting "safe" partners on the basis of appearance, familiarity, or church
      attendance; washing before and after sex to prevent infection; self-treatment
      with antibiotics obtained without a prescription; and visiting the clinic
      frequently for checkups for asymptomatic infections. The authors compare and
      contrast their worldview with the public health concepts of primary and secondary
      STD prevention.

PMID- 11575691
TI  - AOA Presidential Address to the 2001 Congress.

PMID- 11575692
TI  - Optometry's paradigm shift.

PMID- 11575693
TI  - Sensory eye dominance.

PMID- 11575694
TI  - Arranging conditions for learning.

PMID- 11575695
TI  - A summary of the findings from the Collaborative Longitudinal Evaluation of
      Keratoconus (CLEK) Study. CLEK Study Group.
AB  - BACKGROUND: This summary of the Collaborative Longitudinal Evaluation of
      Keratoconus (CLEK) Study includes the study design and results to date. METHODS:
      The CLEK Study is a longitudinal, observational study of 1,209 patients with
      keratoconus. The study's main outcome measures are corneal scarring, visual
      acuity, corneal curvature, and quality of life. RESULTS: These patients' mean age
      at baseline was 39.3 +/- 10.9 years, and they had moderate to severe keratoconus.
      Ninety-five percent of the patients had steep keratometric readings of at least
      45 D, and 78% had best-corrected visual acuity of 20/40 or better in both eyes.
      Sixty-five percent of the patients wore rigid gas-permeable contact lenses in
      both eyes, and most of those (73%) reported that their lenses were comfortable.
      Most rigid gas-permeable contact lens wearers were fitted with apical touch
      (88%). Fifty-three percent had corneal scarring in one or both eyes, and corneal
      scarring was associated with corneal staining, contact lens wear, age, the
      presence of a Fleischer's ring, and a steeper cornea. Corneal scarring was
      associated with decreased high- and low-contrast visual acuity. CONCLUSIONS:
      These results characterize keratoconus patients as rigid gas-permeable contact
      lens wearers with moderately steep corneas. Corneal scarring is associated with
      decreased vision in keratoconus.

PMID- 11575696
TI  - Two differing presentations of optic nerve head drusen.
AB  - BACKGROUND: Optic nerve head drusen was recognized histologically in 1858 by
      Heinrich Muller The majority of optic nerve head drusen cases have been benign in
      nature. However, optic nerve head drusen can be visually devastating. CASE
      REPORTS: Two patients were diagnosed with optic nerve head drusen. They were
      similar in age and each had a best-corrected visual acuity of 20/20 OU. Although
      the diagnosis was the same, the disease affected each person very differently.
      One is currently asymptomatic; the other is legally blind secondary to severely
      constricted visual fields. These cases demonstrate the diversity of visual
      effects produced by optic nerve head drusen. Appropriate ocular workup, including
      visual fields, B-scan ultrasonography, computed tomography, and other tests, are
      presented. CONCLUSION: There is no existing treatment for optic nerve head
      drusen. Proper diagnosis and patient education is the best-available modality of
      care. Patients need to be aware of potential complications which, while rare, can
      affect vision. Visual-field testing can aid in monitoring for subtle changes in
      vision.

PMID- 11575697
TI  - Congenital retinal macrovessel: a case report.
AB  - BACKGROUND: A 24-year-old woman with symptoms of chronic, recurrent headache,
      presumably secondary to migrainous etiology, came to our clinic and was found to
      have a congenital retinal macrovessel encircling an area superior to (but not
      passing through) the macula. CONCLUSIONS: Congenital retinal macrovessels are
      rare, aberrantly large branches of retinal arteries or veins that typically cross
      the horizontal raphe to either supply or drain the macular area. These unusual
      vascular entities must be distinguished from prepapillary vascular loops,
      racemose hemangiomas, Wyburn-Mason syndrome, or other arteriovenous malformations
      with potential neuro-ocular sequelae.

PMID- 11575698
TI  - What is my practice really worth?

PMID- 11575699
TI  - Lifestyle dispensing.

PMID- 11575700
TI  - Documentation guidelines revisited.

PMID- 11575701
TI  - Mechanisms of HIV-1 nucleoside reverse transcriptase inhibitor resistance: is it
      all figured out?
AB  - The mechanistic basis for some examples of HIV-1 NRTI-resistance can be examined
      using altered incorporation of nucleoside analogs and surveying what is known
      about the more recently described mechanisms of chain-terminator removal. The
      complexity of these resistance mechanisms and the interplay with other factors
      that contribute to NRT1 resistance are only just beginning to be appreciated.

PMID- 11575702
TI  - BMS-232632 (Novartis/Bristol-Myers Squibb).
AB  - BMS-232632, an azapeptide HIV protease inhibitor, is in development by Bristol
      Myers Squibb (BMS), under license from Novartis, as a potential treatment for
      HIV/AIDS [248556]. Early preclinical work was carried out by Novartis [248556].
      BMS-232632 was developed as part of a series of compounds (as CGP-73547) and
      evaluated against drug-resistant strains of HIV; the compounds in this series
      belong to a series of azadipeptide analogs and are bis(L-tert-leucine)
      derivatives that exhibit good antiviral activity and satisfactory pharmacokinetic
      profiles [297907]. Novartis subsequently discontinued evaluation of the compound
      in November 1999 [347827]. Phase II trials had already begun by July 1999
      [334335] and BMS expects NDA filing to take place in 2001 [358937]. Use of BMS
      232632 in combination with other antiretroviral agents has demonstrated that it
      may be used in combination with a variety of nucleoside analogs and protease
      inhibitors [298464]. It is thought to have a genotypic resistance profile that
      differs from that of other protease inhibitors [302157]. In February 1999, Lehman
      Brothers predicted the drug had a 30% probability of reaching market, with an
      estimated first launch date in 2001. The analysts predicted peak sales would
      occur in 2007, with sales of $500 million in the US and $300 million in the rest
      of the world at that time [319225].

PMID- 11575703
TI  - DAPD (Emory University/Triangle Pharmaceuticals/Abbott Laboratories).
AB  - Triangle Pharmaceuticals is developing DAPD, a prodrug of the viral replication
      inhibitor dioxolane guanosine, as a potential therapy for HIV and HBV infection.
      Phase I/II dose range studies have commenced for HIV, and clinical development
      for HBV was to have commenced by late 1999 [319145], [319956]. Phase II trials
      are scheduled for the second quarter of 2001. The FDA has designated DAPD as a
      Fast Track product [365894]. DAPD is from a different nucleoside series to FTC
      and CS-92, which are also in development by Triangle. The compound may offer
      advantages over several nucleosides from other series that are already on the
      market because of its unique structure and pharmacological properties [247083].
      Both DAPD and DXG are dioxolane purine nucleoside analogs [319660]. Preclinical
      data suggest DAPD may be of use in combination therapies for HIV-infected
      patients who are therapy-naive, in addition to patients who have previously
      received treatment and including those infected with drug-resistant strains of
      HIV-1 [341145], [341335]. Triangle licensed DAPD from Emory University [216900].
      In June 1999, Triangle and Abbott Laboratories entered into an alliance for the
      development and marketing of six antiviral products, including DAPD [326824].

PMID- 11575704
TI  - TAK-779 (Takeda).
AB  - TAK-779 is a CCR5 antagonist under investigation by Takeda and Kagoshima
      University for the potential treatment of HIV [324663], [342114]. TAK-779
      inhibits chemokine binding to the CCR5 receptor at nanomolar concentrations.
      However, it has no effect on the binding of chemokines to the CXCR4 receptor
      [346835]. A US IND for injectable TAK-779 was filed in june 1999, with Takeda
      initially planning to commence phase I trials in August 1999. However, the FDA
      did not clear the IND and recommended that Takeda altered the study protocol to
      include non-invasive measurement of local toxicities and to evaluate other routes
      of administration. By September 1999, Takeda had conducted some studies in
      response to the FDA's recommendations and had made efforts to develop an oral
      formulation. At this time, the company planned to file a new IND application upon
      completion of the oral formulation [342114]. In August 1995, Lehman Brothers
      predicted potential worldwide peak sales of US $300 million in

PMID- 11575705
TI  - Treatment of transplant rejection: are the traditional immunosuppressants good
      enough?
AB  - Due to the improvement in the understanding of the anti-allogenic immune
      response, the success of transplantation medicine has increased rapidly over the
      last two decades. The knowledge that the T-lymphocyte played an integral role in
      transplant rejection, brought cyclosporine A and FK-506 to the fore as
      therapeutic immunosuppressants. However, the current mainstays in transplant
      rejection are not without their problems and many drug companies are exploring
      the possibilities of improving the available therapies by developing drugs with
      reduced toxicity, improved long-term survival and efficacy against chronic
      rejection and improved immunosuppressive selectivity. The advances in the
      understanding of T-cell activation and lymphocyte trafficking has highlighted
      ways to improve the existing therapies and more selective immunosuppressant
      targets.

PMID- 11575706
TI  - TP-10 (AVANT Immunotherapeutics).
AB  - AVANT Immunotherapeutics is developing TP-10, a recombinant soluble complement
      receptor type 1 (sCR1), for the potential treatment of reperfusion injury
      (following surgery, ischemic disease and organ transplantation), organ rejection,
      acute inflammatory injury to the lungs and autoimmune diseases [348669]. TP-10
      has been awarded Orphan Drug status from the FDA for the prevention and reduction
      of adult respiratory distress syndrome (ARDS) and as a treatment for infants
      undergoing cardiac surgery [180849], [359588]. A placebo-controlled phase II
      trial, conducted at approximately 30 sites in the US and involving approximately
      600 adult patients undergoing cardiac surgery utilizing cardiopulmonary bypass,
      was initiated in November 2000. This safety and efficacy study was designed to
      assess the ability of TP-10 to mitigate the injury to the heart, brain and other
      organs that occurs when patients are placed on cardiopulmonary bypass circuits,
      thus potentially improving postoperative outcomes [391437]. In September 2000,
      the company was planning a double-blind, placebo controlled phase IIb trial in
      infants undergoing cardiac surgery; AVANT expected to initiated in 30 infants in
      January 2001 [395086]. The data from this trial will enable the company to
      further define its clinical endpoints before inititating a pivotal phase III
      trial in 2001 [382529]. A phase I/II trial of TP-10 involving 15 infants, under
      12 months of age, undergoing cardiac surgery for congenital heart defects was
      initiated by the company in September 1999. The trial will evaluate the ability
      of TP-10 to mitigate the injury to the heart and other organs when patients are
      placed on cardiopulmonary bypass circuits [340602]. Enrollment was complete by
      January 2000 [352458]. Phase I safety trials of TP-10, including studies in adult
      patients at risk for adult respiratory distress syndrome (ARDS), adult patients
      with first-time myocardial infarction (heart attack), and pediatric patients
      undergoing cardiac surgery demonstrated that TP-10 is well tolerated. However,
      after completion, in December 1997, of a phase IIa trial in nine patients with
      ARDS, AVANT decided to cease development for this indication. TP-10 was licensed
      to Novartis AG for use in xeno- and allotransplantation in July 1999. Extensive
      animal studies have shown TP-10 to have potential in a wide variety of complement
      mediated conditions, including organ transplantation, multiple sclerosis,
      rheumatoid arthritis and lupus [238093]. Early work demonstrated favorable
      results in animal models of reperfusion injury [180849] and hyperacute xenograft
      rejection in guinea pig to rat and pig to primate organ transplants [191552].
      AVANT has received Notices of Allowance (July 1998) from the USPTO for three
      separate patent applications covering pharmaceutical compositions of TP-10,
      methods of purification and methods of certain TP-10 glycoforms for treating
      diseases or disorders resulting from inappropriate complement activation
      [291776]. In January 1999, the company was awarded US-05856297 which covers
      pharmaceutical compositions of TP-10. US-05856300 was also awarded covering
      compositions and methods of producing the drug [312267].

PMID- 11575707
TI  - Tresperimus (Laboratoires Fournier).
AB  - Tresperimus (LF-08-0299) is an immunosuppressant under development by
      Laboratoires Fournier for its potential use in organ transplant rejection.
      Fournier has commenced phase III trials in the US and Europe [304203].
      Tresperimus began phase I/II trials in 1995 for graft versus host rejection in
      combination with cyclosporine and tacrolimus, but later as first-line therapy. It
      demonstrated efficient immunosuppressive activity in a rat model of cardiac
      rejection [182951]. The company is seeking licensees for the product

PMID- 11575708
TI  - Reverse cholesterol transport and future pharmacological approaches to the
      treatment of atherosclerosis.
AB  - The apparent protective effect of high density lipoprotein cholesterol (HDL) with
      respect to coronary heart disease (CHD) is generally thought to reside in its
      ability to transport cholesterol from peripheral cells to the liver for excretion
      from the body. Knozon as reverse cholesterol transport (RCT), this process
      involves many key steps and lipoprotein interconversions, and there is no
      consensus as to which step is most suitable for possible drug intervention. The
      membrane proteins, scavenger receptor class B, type 1 (SR-B1) and the ATP-binding
      cassette 1 (ABC1), have been strongly implicated as being important in
      cholesterol efflux; the former as a bona fide receptor for HDL and the latter as
      a lipid transporter. Lecithin:cholesterol acyltransferase (LCAT) then esterifies
      the effluxed cholesterol to form cholesteryl esters (Step 2), which are then
      transferred to apoB-containing lipoproteins by cholesteryl ester transfer protein
      (CETP, Step 3). Despite the complexities and uncertainties, drugs should be
      developed which impact all of the above steps, and short-term endpoints need to
      be defined for a cautious, systematic approach to clinical evaluation.

PMID- 11575709
TI  - A clinical focus on statins.
AB  - Clinical trials have demonstrated that inhibitors of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase (statins) significantly reduce cardiovascular
      related morbidity and mortality in patients with and without coronary artery
      disease. Furthermore, statins are currently the most potent cholesterol-lowering
      drugs available. Subanalyses of the LIPID study have shown that patients
      suffering from unstable angina pectoris had at least the same benefit from statin
      therapy as did patients after myocardial infarction. Studies, recently published
      (AVERT or MIRACL) provide more information on the topic of therapy with statins
      in the early phase of acute coronary syndromes.

PMID- 11575710
TI  - Ezetimibe (Schering-Plough).
AB  - Ezetimibe (Sch-58235) is a cholesterol absorption inhibitor being developed by
      Schering-Plough for the potential treatment of atherosclerosis and
      hypercholesterolemia. By January 2000, it was in phase III trials in the US
      [353762], [363364]. Schering-Plough is studying ezetimibe as a monotherapy for
      lowering lipid levels and, by February 2000, it was also planning combination
      studies with commonly used statin (HMG-CoA reductase inhibitor) therapies. The
      company believes that ezetimibe will have additive effects with the statins,
      inhibiting the absorption of cholesterol in the intestine while the statins work
      by inhibiting the production of cholesterol in the liver [363364]. In May 2000,
      Merck signed an agreement with Schering-Plough to develop and market in the US a
      once-daily, fixed-combination tablet with simvastatin (Zocor) [368021]. This
      combination has been shown to improve LDL reduction to 52% as compared to 35%
      with Zocor alone [375966].

PMID- 11575711
TI  - S-8921 (Shionogi).
AB  - S-8921 is a sodium/bile acid transport inhibitor under development by Shionogi
      for the potential treatment of hyperlipidemia. As of June 2000, phase I trials
      had commenced in Japan and were planned in Europe [370602]. S-8921 acts by
      altering sodium-dependent transport mechanisms of the brush-borders in the
      intestinal mucosa, causing bile acids that re-enter the intestine to be excreted
      rather than reabsorbed [281476].

PMID- 11575712
TI  - Differential gene expression--how to find new analgesic targets.

PMID- 11575714
TI  - Donitriptan (Pierre Fabre).
AB  - Pierre Fabre is developing donitriptan, a piperazide 5-HT1D agonist, as a
      potential treatment for migraine [175854]. In January 2001, donitriptan had
      completed phase I trials for migraine and was scheduled to enter phase II
      development [396027]. This compound has an increased potency and, importantly,
      markedly higher intrinsic activity in comparison to the well described tryptamine
      derivatives, naratriptan, zolmitriptan and sumatriptan [295769].

PMID- 11575713
TI  - Cannabinoids and pain.
AB  - Recent advances have dramatically increased our understanding of cannabinoid
      pharmacology: the psychoactive constituents of Cannabis sativa have been
      isolated, synthetic cannabinoids described and an endocannabinoid system
      identified, together with its component receptors, ligands and their
      biochemistry. Strong laboratory evidence now underwrites anecdotal claims of
      cannabinoid analgesia in inflammatory and neuropathic pain. Sites of analgesic
      action have been identified in brain, spinal cord and the periphery, with the
      latter two presenting attractive targets for divorcing the analgesic and
      psychotrophic effects of cannabinoids. Clinical trials are now required, but are
      hindered by a paucity of cannabinoids of suitable bioavailability and therapeutic
      ratio.

PMID- 11575715
TI  - MT-500 (POZEN).
AB  - MT-500 (formerly RS-127445) is a 5-HT2B antagonist being developed for the
      prophylactic treatment of migraine. POZEN acquired MT-500 from Roche in November
      1999, and assumed full responsibility for its development for migraine
      propylaxis. Roche may elect to reacquire the compound at certain stages. The
      company expected to commence phase II trials during the first half of 2000
      [348204]. POZEN has three other compounds, MT-400, MT-300 and MT-100, in phases
      I, II and III, respectively, for the treatment of acute migraine. Before
      outlicensing the compound, Roche Bioscience had completed phase I trials with MT
      500 which indicate that it has a favorable side effect and safety profile
      [348204]. In January 2001, US Bancorp Piper Jaffray predicted phase II
      development beginning in 2001, with a launch in 2006 [396247].

PMID- 11575716
TI  - Recent success with the tyrosine kinase inhibitor STI-571--lessons for targeted
      therapy of cancer.

PMID- 11575717
TI  - CT-2584 (Cell Therapeutics).
AB  - CT-2584, an anticancer agent that inhibits phospholipid signaling, is under
      development by Cell Therapeutics Inc (CTI) as a potential treatment for various
      types of cancer. Phase II trials are underway for the treatment of prostate
      cancer and soft-tissue sarcoma [306617], [324290]. According to CIBC World
      Markets, completion of enrolment for these trials was expected in the fourth
      quarter of 2000. Furthermore, the initiation of phase II/III trials in
      combination with taxotere for the treatment of prostate cancer was anticipated in
      the second half of 2000, as were phase I/II trials in combination with cisplatin
      for the treatment of other cancers, including lung cancer [396582]. Results of a
      phase II study in patients with soft-tissue sarcomas evaluating pharmacokinetics,
      tolerance and therapeutic activity were presented at the 2000 American Society of
      Clinical Oncology (ASCO) meeting [367283]. Further data are expected to be
      presented at the ASCO meeting in May 2001 [396582]. Cell Therapeutics is seeking
      development and commercialization partners for CT-2584 [386398].

PMID- 11575718
TI  - ZD-1839 (AstraZeneca).
AB  - AstraZeneca is developing ZD-1839, an inhibitor of epidermal growth factor
      receptor 1 (EGFR1) tyrosine kinase, for potential treatment of cancers which
      overexpress EGF receptors, including non-small cell lung cancer (NSCLC) and
      pancreatic cancer [196279], [270898]. Phase III studies had started by August
      2000 [349551], [350295], [353050], [377656], with first results being expected at
      the 2001 meetings of the American Association for Cancer Research (AACR) and the
      American Society for Clinical Oncology (ASCO). The US FDA has issued ZD-1839 with
      Fast Track status [350295], [353050]. In September 2000, the company expected
      global NDA filing to take place at the end of 2001, with launch in the next four
      to five years [383469]. In January 1999, ABN Amro predicted sales of US $25
      million in 2004 rising to $82 million in 2005 [316250]. In March 1999, Lehman
      Brothers predicted a 30% probability that the drug would reach worldwide markets
      and be launched onto the market in 2004 [336599]. In June 2000, Deutsche Bank
      predicted sales of US $8 million in 2002, rising to $100 million in 2003
      [374500]. In September 2000, analysts Merrill Lynch predicted a launch in 2002
      with sales estimated at UK 50 million  pounds, rising to 360 million pounds in
      2004, while in December 2000, the analysts predicted a filing date in the fourth
      quarter of 2001 [383742], [396280]. Also in December 2000, Lehman Brothers
      predicted a filing date late in 2001, and a possible Fast Track review. They also
      estimated peak sales of US $1 billion [394606].

PMID- 11575719
TI  - Dual targeting properties of the N-terminal signal sequence of Arabidopsis
      thaliana THI1 protein to mitochondria and chloroplasts.
AB  - thi1 has been recently isolated from Arabidopsis thaliana and is probably
      involved in both thiamine biosynthesis and as protection of organellar DNA from
      damage. Studies of thiamine biosynthesis in plants suggests a plastid location
      for the pathway, which is in agreement with the predicted THI1 N-terminal
      chloroplastic transit peptide (TP). On the other hand, thiamine is synthesized in
      mitochondria in yeast cells. Interestingly, A. thaliana thi1 cDNA complements a
      yeast strain disrupted for the homologous gene. Analysis of THI1 amino acid
      sequence revealed the presence of a putative amphiphilic alpha-helix, which is
      typical for mitochondrial presequences, located downstream of the chloroplast
      transit peptide. To define the putative role of the two predicted targeting
      sequences in tandem, we produced two chimeric genes encompassing the
      chloroplastic THI1 TP and either 4 or 27 (including the putative mitochondrial
      presequence) N-terminal residues of the mature THI1, both linked to the reporter
      (gusA) gene. Analysis of GUS distribution in subcellular fractions of transgenic
      plants revealed that in the construct retaining only 4 residues of mature THI1,
      GUS was found in the chloroplastic fraction. Extension of the THI1 transit
      peptide to 27 residues of the mature protein allowed import and processing of GUS
      into both mitochondria and chloroplasts. Direct analysis by immunogold-labeling
      with an anti-THI1 polyclonal antibody identified THI1 in both organelles in
      Arabidopsis. We also provide evidence that the precursors of both organellar
      isoforms are encoded by a single nuclear transcript. Thus, THI1 is targeted
      simultaneously to mitochondria and chloroplasts by a post transcriptional
      mechanism.

PMID- 11575720
TI  - cDNA cloning of two isoforms of ornithine carbamoyltransferase from Canavalia
      lineata leaves and the effect of site-directed mutagenesis of the carbamoyl
      phosphate binding site.
AB  - The immunoscreening method was used to isolate cDNAs of 1323 bp (ClOCT1) and 1433
      bp (ClOCT2) encoding two ornithine carbamoyltransferases (OCT, EC 2.1.3.3) from
      the cDNA expression library of Canavalia lineata leaves constructed in a
      lambdaZAP Express vector. ClOCT1 and ClOCT2 encode 359 and 369 amino acids,
      respectively. The N-terminals of deduced amino acid sequences of the two cDNAs
      showed typical features of the transit peptide of chloroplast targeting proteins.
      The ornithine-binding domain (FMHCLP) and catalytic domain (HPXQ) of ClOCT1 and
      ClOCT2 and the carbamoyl phosphate (CP)-binding site of ClOCT1 (SMRTR) are
      identical to OCTs of other plant species, pea and Arabidopsis thaliana. However,
      the CP-binding site sequence of ClOCT2, SLRTH, has not yet been reported. Both
      ClOCT1 and ClOCT2 cDNAs were expressed in Escherichia coli BL21 (DE3) by using
      expression vector pET30a. Recombinant ClOCT1 protein showed 14 times higher
      ornithine-dependent OCT activity than canaline-dependent OCT activity. In
      contrast, recombinant ClOCT2 protein showed 13 times higher canaline-dependent
      OCT activity than ornithine-dependent OCT activity. The two amino acids of the CP
      binding site of ClOCT2 (SLRTH) were combinatorially changed to those of the CP
      binding site of ClOCT1 (SMRTR) by site-directed mutagenesis. When Leu-118 of
      ClOCT2 was changed to Met, ornithine-dependent activity was increased
      significantly. It is assumed that the substrate specificity of ClOCT1 or ClOCT2
      proteins partially depends on the amino acid sequence of the CP-binding site.

PMID- 11575721
TI  - Molecular cloning of a novel pathogen-inducible cDNA encoding a putative acyl-CoA
      synthetase from Capsicum annuum L.
AB  - By means of differential display, a pool of salicylic acid (SA)-induced mRNAs
      were identified and subsequently their cDNAs were isolated from a cDNA library
      prepared from SA-induced leaf tissues of hot pepper. One of these cDNA clones,
      designated CaSIG4, was 1900 bp and contained an open reading frame encoding 523
      amino acids with a calculated molecular mass of 56.3 kDa. The predicted amino
      acid sequence of CaSIG4 showed high sequence similarity to the AMP-binding
      protein family of both prokaryotic and eukaryotic acyl-CoA synthetases. CaSIG4
      transcripts accumulated rapidly after SA treatment and in response to both
      incompatible and compatible interactions with Xanthomonas campestris pv.
      vesicatoria race 1. To investigate the cis-acting elements mediating CaSIG4
      expression, the CaSIG4 5'-flanking region was isolated by inverse PCR. Database
      searches indicated that a potential cis-regulatory element is almost identical to
      the consensus core sequences ACC(A/T)ACC(A/C) which are conserved among promoters
      of other phenylpropanoid biosynthetic genes. The subcellular localization of the
      CaSIG4 protein was studied by using a soluble modified GFP gene fusion delivered
      into epidermal cells of onion by biolistic bombardment. The CaSIG4-smGFP fusion
      protein was localized to the plasma membrane. Taken together, CaSIG4 encoding a
      putative acyl-CoA synthetase could function as a plasma membrane-bound protein
      with a role in signaling in plant defense.

PMID- 11575722
TI  - Establishment of Arabidopsis thaliana ribosomal protein RPL23A-1 as a functional
      homologue of Saccharomyces cerevisiae ribosomal protein L25.
AB  - Arabidopsis thaliana ribosomal protein (r-protein) RPL23A-1 shows 54% amino acid
      sequence identity to the Saccharomyces cerevisiae equivalent r-protein, L25.
      AtRPL23A-1 also shows high amino acid sequence identity to members of the L23/L25
      r-protein family in other species. R-protein L25 in S. cerevisiae has been
      identified as a primary rRNA-binding protein that directly binds to a specific
      site on yeast 26S rRNA. It is translocated to the nucleolus where it binds to 26S
      rRNA during early large ribosome subunit assembly; this binding is thought to
      play an important role in ribosome assembly. The S. cerevisiae mutant strain
      YCR61 expresses L25 when grown on galactose, but not glucose, medium.
      Transformation of YCR61 with a shuttle vector containing the AtRPL23A-1 cDNA
      allowed transformed colonies to grow in and on glucose selection medium. R
      protein AtRPL23A-1 can complement the L25 mutation, demonstrating the functional
      equivalence of the two r-proteins and introducing AtRPL23A-1 as the first plant
      member of the L23/L25 r-protein family.

PMID- 11575723
TI  - Expression and phylogeny of the multiple antenna genes of the low-light-adapted
      strain Prochlorococcus marinus SS120 (Oxyphotobacteria).
AB  - In contrast to typical cyanobacteria, Prochlorococcus strains possess an
      intrinsic divinyl-chlorophyll (Chl) a/b-protein complex instead of phycobilisomes
      as the major light-harvesting system. These pigment-protein complexes are encoded
      by a variable number of pcb genes depending on the ecotype to which the
      Prochlorococcus strain belongs: low-light-adapted strains possess several pcb
      gene copies whereas only a single copy is present in high-light-adapted strains.
      In this study, the light-regulated expression of the seven pcb genes of
      Prochlorococcus marinus SS120 was examined. The pcbF gene was found to exhibit a
      high turnover and its mRNA could only be detected as a degraded product under all
      light conditions. Steady-state levels of transcripts originating from the six
      other pcb gene copies varied over several orders of magnitude but were not
      significantly differentially regulated by light intensity. Transcript levels of
      most pcb genes increased between 4.5 and 8.5 micromol quanta m(-2) s(-1), peaked
      at 45 micromol m(-2) s(-1) and decreased at the highest irradiance (72 micromol
      m(-2) s(-1)). A phylogenetic analysis of the Pcb proteins and other members of
      the six-helix Chl protein superfamily revealed that PcbC and PcbG make a separate
      cluster with regard to the other Pcbs from SS120. In contrast, Pcb sequences from
      four high-light-adapted Prochlorococcus sp. strains were found to cluster
      together and to be less variable than SS120 Pcbs. Thus, pcb genes likely evolved
      at a different rate in the two Prochlorococcus ecotypes. Their early
      multiplication and diversification is likely a key factor in the successful
      adaptation of some genotypes to very-low-light conditions.

PMID- 11575724
TI  - A library of Arabidopsis 35S-cDNA lines for identifying novel mutants.
AB  - We have developed a system to over-express or co-suppress random cDNAs in
      Arabidopsis thaliana upon Agrobacterium tumefaciens-mediated transformation. We
      constructed a binary vector containing a novel Arabidopsis cDNA library driven by
      the cauliflower mosaic virus (CaMV) 35S promoter. The vector, 35SpBARN, offers in
      terra selection with glufosinate ammonium (BASTA) and the ability to identify the
      cDNA insert using PCR with flanking primers. We introduced this overexpression
      library into Arabidopsis and selected over 30,000 transformants. A random sample
      of 50 T1 plants was analyzed to determine the quality of the cDNA library in
      planta. About 90% of T1 plants in the collection have inserts, the average insert
      size is ca. 1.1 kb, and ca. 43% of these inserts appear to encode full-length
      proteins. T1 plants were screened for visible abnormalities, and one mutant, V5,
      was chosen for further study. This mutant displays a pale green phenotype, and
      its transgene contains a partial petH cDNA encoding chloroplast ferredoxin-NADP+
      reductase (EC 1.18.1.2). This construct co-suppresses the endogenous petH
      transcript. We recapitulated the mutant phenotype by expressing either the full
      length or truncated petH cDNA from the CaMV 35S promoter in wild-type
      Arabidopsis. Our results indicate that co-suppressing endogenous genes can cause
      dominant phenotypes as expected. As we have also used the 35SpBARN vector to
      successfully over-express other transcripts in planta, we predict that this
      system will be generally useful for identifying genes that yield phenotypes upon
      over-expression as well.

PMID- 11575725
TI  - Tissue-specific and developmental-specific expression of an Arabidopsis thaliana
      gene encoding the lipoamide dehydrogenase component of the plastid pyruvate
      dehydrogenase complex.
AB  - We describe an Arabidopsis thaliana gene, ptlpd2, which codes for a protein with
      high amino acid similarity to lipoamide dehydrogenases (LPDs) from diverse
      species. Ptlpd2 codes for a precursor protein possessing an N-terminal extension
      predicted to be a plastid-targeting signal. Expression of the ptlpd2 cDNA in
      Escherichia coli showed the encoded protein possessed the predicted LPD activity.
      PTLPD2 protein, synthesized in vitro, was efficiently imported into isolated
      chloroplasts of Pisum sativum and shown to be located in the stroma. In addition,
      fusion proteins containing the predicted transit peptide of PTLPD2 or the entire
      protein fused at the N-terminus with the green fluorescent protein (GFP), showed
      accumulation in vivo in chloroplasts but not in mitochondria of A. thaliana.
      Expression of ptlpd2 was investigated by introducing ptlpd2 promoter-beta
      glucuronidase (GUS) gene fusions into Nicotiana tabacum. GUS expression was
      observed in seeds, flowers, root tips and young leaves. GUS activity was highest
      in mature seeds, decreased on germination and increased again in young leaves.
      Expression was also found to be temporally regulated in pollen grains where it
      was highest in mature grains at dehiscence. Database searches on ptlpd2 sequences
      identified a second A. thaliana gene encoding a putative plastidial LPD and two
      genes encoding proteins with high similarity to the mitochondrial LPD of P.
      sativum.

PMID- 11575726
TI  - Expression of the FAE1 gene and FAE1 promoter activity in developing seeds of
      Arabidopsis thaliana.
AB  - Plant fatty acid elongase which catalyzes very-long-chain fatty acid (VLCFA)
      biosynthesis is a membrane-bound multienzyme complex. It is composed of four
      enzymes, a 3-ketoacyl-CoA synthase (condensing enzyme), a 3-ketoacyl-CoA
      reductase, a 3-hydroxyacyl-CoA dehydrase, and an enoyl-CoA reductase required for
      completion of each step of 2-carbon elongation of fatty acids. To improve our
      understanding of the overall regulation of the fatty acid elongase, we
      investigated the spatial and temporal expression of its key component, the FAE1
      condensing enzyme, and examined the activity of the promoter of the FAE1 gene in
      Arabidopsis. In situ hybridization results revealed that FAE1 transcripts were
      found exclusively in the embryo. RNA blot analysis and histochemical analysis of
      GUS activity in pFAE1::GUS transgenic Arabidopsis lines demonstrated that the
      FAE1 gene was already transcribed in the early torpedo stage embryos 4-5 days
      after flowering, with transcription reaching its peak 9-11 days after flowering.
      VLCFA deposition closely paralleled FAE1 transcript accumulation. FAE1 promoter
      was highly active and embryo-specific. Because its timing coincides with the
      period of major storage lipid accumulation, and because its in vivo activity in
      Arabidopsis is superior to the napin promoter, FAE1 promoter may be ideal for
      genetic engineering of seed oil composition.

PMID- 11575727
TI  - Manipulation of the napin primary structure alters its packaging and deposition
      in transgenic tobacco (Nicotiana tabacum L.) seeds.
AB  - Napin is a 2S storage protein found in the seeds of oilseed rape (Brassica napus
      L.) and related species. Using protein structural prediction programs we have
      identified a region in the napin protein sequence which forms a 'hydrophilic
      loop' composed of amino acid residues located at the protein surface. Targeting
      this region, we have constructed two napin chimeric genes containing the coding
      sequence for the peptide hormone leucine-enkephalin as a topological marker. One
      version has a single enkephalin sequence of 11 amino acids including linkers and
      the second contains a tandem repeat of this peptide comprising 22 amino acids,
      inserted into the napin large subunit. The inserted peptide sequences alter the
      balance of hydrophilic to hydrophobic amino acids and introduce flexibility into
      this region of the polypeptide chain. The chimeric genes have been expressed in
      tobacco plants under the control of the seed-specific napA gene promoter.
      Analyses indicate that the engineered napin proteins are expressed, transported,
      post-translationally modified and deposited inside the protein bodies of the
      transgenic seeds demonstrating that the altered napin proteins behave in a
      similar fashion to the authentic napin protein. Detailed immunolocalisation
      studies indicate that the insertion of the peptide sequences has a significant
      effect on the distribution of the napin proteins within the tobacco seed protein
      bodies.

PMID- 11575728
TI  - Differential expression of two cinnamate 4-hydroxylase genes in 'Valencia' orange
      (Citrus sinensis Osbeck).
AB  - Two different full-length cDNAs for cinnamate 4-hydroxylase (C4H1 and C4H2) were
      isolated from Citrus sinensis Osbeck cv. Valencia libraries. C4H1 (1708 bp) and
      C4H2 (1871 bp) share only 65% identity on nucleotide and 66% identity on the
      amino acid level, respectively. C4H1 is most homologous to a cinnamate 4
      hydroxylase sequence from French bean (Phaseolus vulgaris), but codes for a
      unique N-terminus. C4H2 shows highest similarity to a poplar (Populus
      kitakamiensis) sequence, but also shows a unique N-terminus. The two genes are
      expressed differentially in orange flavedo, C4H2 is constitutive, C4H1 is wound
      induced. In competitive RT-PCR, the mRNA for both genes in wounded and untreated
      tissue was quantified. C4H1 is strongly wound-inducible from 'not detectable' to
      about 35 fg mRNA per 50 ng total RNA 8 h after wounding. The first detectable
      C4H1 mRNA was found 4 h after wounding. After reaching peak levels 4 h later the
      levels slightly declined, but stayed elevated until the end of the experiment (48
      h). C4H2 is expressed 3-10 times higher than wound-induced C4H1 even in the
      control sample; wounding transiently increases the level of expression another 2
      3 times. The existence of different N-termini and their effects on the possible
      role of both genes in phenylpropanoid pathways is discussed.

PMID- 11575729
TI  - Beta-cyanoalanine synthase and cysteine synthase from potato: molecular cloning,
      biochemical characterization, and spatial and hormonal regulation.
AB  - Beta-cyanoalanine synthase (CAS, L-3-cyanoalanine synthase; EC 4.4.1.9) is the
      most important enzyme in cyanide metabolism. In addition to CAS, cysteine
      synthase (CS, EC 4.2.99.8) possesses CAS activity. To explore the physiological
      significance of cyanide metabolism, we isolated the cDNA clones corresponding to
      purified CAS (designated PCAS-1 and PCAS-2) and CS (designated PCS-1 and PCS-2)
      from potato using the information of these amino acid sequences. The recombinant
      proteins of PCS-1, PCS-2 and PCAS-1 catalyzed both CAS and CS reactions, although
      the ratios between CAS and CS activity were remarkably different. PCAS-1
      preferred the substrates for the CAS reaction to the substrates for the CS
      reaction. From the kinetic characters and homology of amino acid sequences with
      known CS-like proteins, PCS-1, PCS-2 and PCAS-1 were identified as cytosolic CS,
      plastidic CS and mitochondrial CAS, respectively. The highest level of CAS
      activity, CAS protein and its mRNA were detected in potato buds. Stimulation of
      CAS activity and protein accumulation by ethylene without the concomitant
      increase of its mRNA suggested that ethylene induces CAS protein accumulation at
      the post-transcriptional level.

PMID- 11575730
TI  - Switching antidepressants for treatment-resistant major depression.
AB  - A substantial proportion of patients suffering from major depression experience
      insufficient clinical response, despite appropriate treatment. Switching to a
      different monotherapy antidepressant medication is the preferred option for many
      patients and clinicians. The possible advantages of switching to a different
      monotherapy, as compared with adding a second agent (i.e., augmenting or
      combining), include reduced medication costs, fewer drug interactions, better
      adherence, and less patient burden over time. Response rates for switching, are
      based largely on open trials, which reveal a response rate of approximately 50%.
      These response rates are comparable to the response rates reported with
      augmentation or combination, again established largely by noncomparative open
      trials. This review article summarizes clinical considerations and available
      evidence regarding switching antidepressants in the treatment of major
      depression. Practical issues, such as when to consider switching and how to
      switch from one medication to another, are addressed.

PMID- 11575731
TI  - Management of treatment-resistant depression: psychotherapeutic perspectives.
AB  - Treatment-resistant depression is a heterogeneous condition that occurs within a
      psychosocial milieu. The impact of prior pharmacologic interventions may have
      been adversely affected by a poor therapeutic alliance, low social support, life
      stress, or chronic adversity and cognitive or personality factors such as
      neuroticism or pessimism. This article considers the psychosocial factors that
      predispose to treatment-resistant depression and the psychotherapeutic principles
      thought to be helpful in both shorter- and longer-term treatment plans. We focus
      on the interpersonal, cognitive, and behavioral forms of treatment that
      constitute the depression-focused psychotherapies, which have been studied in
      major depressive disorder. Also discussed are modifications in treatment planning
      necessary to take into account the complexity of treatment-resistant depression.

PMID- 11575732
TI  - Using treatment algorithms for the effective management of treatment-resistant
      depression.
AB  - Increasingly, clinicians are looking to evidence-based medicine for information
      about treatment options. Treatment algorithms have been used with a variety of
      psychiatric disorders to assist physicians in making treatment decisions. The
      direct, prescriptive nature of algorithms also makes them suitable for use in
      treatment-resistant depression. Two major projects, the Texas Medication
      Algorithm Project and Sequenced Treatment Alternatives to Relieve Depression,
      have begun to address the questions of sequenced treatment options. Future
      directions for algorithm development and implementation are discussed.

PMID- 11575733
TI  - Augmentation and combination strategies in treatment-resistant depression.
AB  - A substantial proportion of depressed patients show only partial or no response
      to antidepressants, and even among responders to antidepressant treatment,
      residual symptoms are rather common. When depressions do not respond adequately
      to treatment with an antidepressant, clinicians may choose to keep the same
      antidepressant and add another "augmenting" compound. Such augmentation
      strategies involve the use of a pharmacologic agent that is not considered to be
      a standard antidepressant but may boost or enhance the effect of an
      antidepressant. Alternatively, clinicians may choose combination strategies, in
      which they combine the antidepressant that did not produce adequate response with
      another antidepressant, typically of a different class. There are only a few
      controlled clinical trials of these 2 strategies among patients with treatment
      resistant depression or among patients who have only partially benefited from
      antidepressant treatment. Most of the time, clinicians' decisions are, therefore,
      guided by anecdotal reports, case series, and by some relatively smaller,
      uncontrolled clinical trials. These augmentation and combination strategies
      appear to be relatively safe and effective approaches to treatment-resistant
      depressions, although there is a relative paucity of controlled studies to
      support their efficacy. These strategies typically aim at obtaining a different
      neurochemical effect than the one obtained with the antidepressant that has not
      produced adequate response. While drug-drug interactions may limit the use of
      some of these strategies, the potential loss of partial benefit from the failed
      drug inherent in switching may increase the acceptability of augmentation and
      combination strategies among partial responders. Further studies are clearly
      needed to evaluate the comparative efficacy and tolerability of these different
      approaches in treatment-resistant depressions.

PMID- 11575734
TI  - Tuberculosis today: a brief review.

PMID- 11575735
TI  - In vitro activity of Melaleuca alternifolia (tea tree) oil against bacterial and
      Candida spp. isolates from clinical specimens.
AB  - This study investigates the in vitro activity of tea tree oil (TTO) against a
      range of wild strains of microorganisms isolated from clinical specimens of leg
      ulcers and pressure sores. The antimicrobial effectiveness of TTO is determined
      in terms of minimum inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC) or minimum fungicidal concentration (MFC). The isolates
      include methicillin-resistant Staphylococcus aureus (MRSA), S. aureus, faecal
      streptococci, beta-haemolytic streptococci, coagulase-negative staphylococci,
      Pseudomonas spp. and coliform bacilli. Eleven Candida spp. isolates from skin and
      vaginal swabs also are tested. Using an agar dilution assay, the MICs of TTO in
      88 out of 90 isolates was 0.5-1.0% (v/v), whilst with P. aeruginosa it was >2%
      (v/v). A broth microdilution method was used to determine MIC and minimum cidal
      concentration (MCC) of 80 isolates. In 64 isolates, TTO produced an inhibitory
      and cidal effect at 3% and 4% (v/v), respectively. S. aureus and Candida spp.
      were the most susceptible to TTO, with MICs and MBCs of 0.5% and 1%,
      respectively. P. aeruginosa and the faecal streptococci isolates, with MICs and
      MBCs of >8%, were resistant to TTO.

PMID- 11575736
TI  - Oxoid aura system as a semi-automated, standard antimicrobial susceptibility test
      method.
AB  - The need for a national strategy for antimicrobial resistance surveillance is
      well recognised. The diversity of susceptibility testing methods in the UK has
      led to the development of a standard method by the British Society for
      Antimicrobial Chemotherapy. Here, use of an early manual-measurement Oxoid Aura
      system is compared with an in-house, non-standard method. The usefulness of such
      a system in the evaluation of antibiotic susceptibility data collected for
      Staphylococcus aureus, including methicillin-resistant S. aureus, is also
      examined. An automated version of this equipment is now available.

PMID- 11575737
TI  - Improved detection of Mycobacterium spp. using the Bactec MGIT 960 system.
AB  - Until 1987, the notification rate for mycobacterial infection was on the decline;
      however, it now appears to be increasing once more. The reason for this may be
      multifactoral and include improved reporting of diagnosed cases, increased
      infection of an ageing population, homelessness, immunosuppression (e.g. due to
      human immunodeficiency virus infection), and immigration of people from countries
      where tuberculosis is endemic. This rising incidence and the increasing
      importance of resistant organisms mean that rapid identification by the clinical
      microbiology laboratory is required, and this is where an automated detection
      system can be an advantage. Over a two-year period, 2743 clinical specimen were
      examined for Mycobacterium spp. using the Bactec MGIT 960, and 286 were positive.
      Time to detection ranged from three to 14 days (mean: 9.3 days), and M.
      tuberculosis was recovered from 214 (75.5%). Contamination rate was higher (8.6%)
      than with manual methods, however. On balance, the Bactec MGIT 960 system proved
      a valuable tool in the routine microbiology laboratory.

PMID- 11575738
TI  - Assessment of murine lung tumour development: a comparison of two techniques.
AB  - Two techniques (surface photographic analysis [SPA] and microscopic tumour
      analysis [MTA]) are described for assessing the stage of tumour development
      induced by intraperitoneal 4-(methyl nitrosamino)- 1-(3 pyridyl)-1-butanone in
      syngeneic A/J mice. Parameters used to assess the number and size of tumours were
      surface tumour count (STC), surface tumour area (STA). and relative tumour
      surface area (RTSA)--all using SPA; and mean tumour count (MTC), mean tumour
      area, and relative tumour area (RTA)--all using MTA. In a study examining the
      possible effects of Millipore chamber implantation on lung tumours, the stage of
      tumour development was assessed in 239 mice using both SPA and MTA. Statistically
      significant correlations (Spearman-Rank) were apparent between the derived
      parameters: STC vs. MTC (r = 0.6, P <0.0001); STA vs. mean tumour area (r = 0.5,
      P <0.0001); RTSA vs. RTA (r = 0.4, P <0.0001). Therefore, it is concluded that
      SPA--the simpler technique--is an appropriate method for assessing the stage of
      tumour development in this model.

PMID- 11575739
TI  - Effect of pleuran (beta-glucan from Pleurotus ostreatus) on the antioxidant
      status of the organism and on dimethylhydrazine-induced precancerous lesions in
      rat colon.
AB  - The effect of pleuran (beta-1,3-D-glucan isolated from the oyster mushroom
      Pleurotus ostreatus) on the antioxidant status of the organism and on the
      development of precancerous aberrant crypt foci (ACF) lesions in the colon is
      studied in the male Wistar rat. A diet containing either 10% pleuran or 10%
      cellulose was compared with a cellulose-free diet and both were found to
      significantly reduced conjugated diene content in erythrocytes and in liver.
      Particularly significant was the reduction of conjugated dienes in the colon
      following pleuran administration. Diets containing cellulose and pleuran reduced
      glutathione peroxidase (GSH-PX) activity and increased catalase activity in
      erythrocytes. Pleuran increased superoxide dismutase (SOD) and GSH-PX activity
      (compared with the cellulose diet), and glutathione reductase activity (compared
      with the cellulose-free diet) in liver; and both diets reduced glutathione levels
      significantly in the colon. ACF lesions developed in the colon of all animals fed
      a cellulose-free diet; however, the incidence was reduced to 64% and 60%
      following the cellulose and pleuran diets, respectively. The highest average
      count of the most frequent small ACF lesions--and highest total count--was seen
      in animals fed a cellulose-free diet. Although ACF lesions were reduced by the
      cellulose diet, the more significant reduction statistically (>50%) was achieved
      with the pleuran diet.

PMID- 11575740
TI  - Effect of nitric oxide and malondialdehyde on sister-chromatid exchanges in
      breast cancer.
AB  - Nitric oxide (NO) and malondialdehyde (MDA) play a significant role in DNA
      damage, sister-chromatid exchanges (SCEs) and carcinogenesis. Here, we determine
      plasma NO and MDA to evaluate their role in carcinogenesis and their effect on
      the frequency of SCEs in 45 female breast cancer patients and in 35 age- and sex
      matched controls. Plasma NO (P<0.01) and MDA (P<0.001) was significantly higher
      in the breast cancer group, and a direct correlation were found between plasma NO
      and MDA concentration and tumour grade. Patients with stage II disease showed the
      highest levels of both NO and MDA, compared with controls. Simultaneously, SCE
      frequency per lymphocyte in the breast cancer group was found to be significantly
      (P<0.001) higher; the greatest increase being found in patients with stage IV
      disease. Positive correlation was found between SCEs and both NO and MDA in the
      breast cancer group; however, both NO and MDA production decreased with
      increasing severity of the disease. Lower NO production in stage IV disease may
      be due to lower expression of nitric oxide synthase (NOS), further facilitating
      the production of superoxide anions (O2*-). The reaction between NO and O2*-
      results in peroxynitrite (OONO-) formation, which works efficiently at the
      molecular level and may induce higher SCE frequency. This work suggests that
      further cytogenetic and molecular study is required to provide definite answers
      for the therapeutic use of NO in breast cancer.

PMID- 11575741
TI  - TGF-beta1 is elevated in breast cancer tissue and regulates nitric oxide
      production from a number of cellular sources during hypoxia re-oxygenation
      injury.
AB  - Cellular response to treatment is dependent on the metabolic preconditioning of
      individual cells, which is a reflection of environmental conditions. Within solid
      tumours there are areas of different oxygen tension, which, we hypothesise, may
      indicate that cells are exposed to conditions that change continually. Other
      characteristics of the solid-tumour microenvironment include the production of
      growth factors, one of which is transforming growth factor (TGF)-beta1. As part
      of this study, we measured TGF-beta1 and found it raised in the serum of breast
      cancer patients compared with controls (98.24+/-13.25 vs. 48.87+/-12.14 ng/mL; P
      < 0.05; n = 7), and in the conditioned medium of breast tumour explant tissue
      compared with matched normal tissue (21.1+/-5.3 vs. 4.7+/-1.2 ng TGF-beta1/gram
      of tissue; P < 0.05; n = 11). Nitric oxide (NO) is a cytotoxic molecule produced
      by a large number of cells and thought to have antimetastatic properties. In
      order to observe the effect of conditions within breast tumours on NO production,
      we exposed macrophages, endothelial cells and tumour cells to hypoxia re
      oxygenation in vitro, both in the presence and absence of TGF-beta1. Hypoxia
      stimulated increased NO production in both macrophages (normoxia: 0.34+/-0.04
      nmol/L nitrite vs. hypoxia: 1.04+/-0.18 nmol/L nitrite; P < 0.05) and endothelial
      cells (normoxia: 0.02+/-0.01 nmol/L nitrite vs. hypoxia: 0.21+/-0.07 nmol/L
      nitrite; P < 0.05). NO production in macrophages, endothelial cells and tumour
      cells was reduced significantly following hypoxia in the presence of TGF-beta1 in
      a concentration-dependent manner. These results suggest that, within breast
      tumours, tumour-derived TGF-beta1 in combination with environmental conditions
      may result in decreased local NO production, which could have implications for
      tumour growth.

PMID- 11575742
TI  - Hybrid capture as a means of detecting human papillomavirus DNA from liquid-based
      cytology specimens: a preliminary evaluation.
AB  - The connection between human papillomavirus (HPV) and cervical cancer is well
      documented, as is the benefit of an adjunctive, standardised objective test to
      complement cervical screening. Here, 197 liquid-based cytology (LBC) specimens
      previously processed for cytological examination (75 negative, 108
      borderline/mild dyskaryosis, and 14 moderate/severe dyskaryosis) are examined for
      the presence of HPV using a hybrid capture assay. Of the 197 specimens tested for
      HPV DNA, 97 (49.2%) were positive using the combined high/low-risk probe, and 59
      (29.9%) were negative cytologically and with the hybrid capture HPV test;
      however, 16/175 (21.3%) specimens classified as negative cytologically with LBC
      proved positive for HPV by hybrid capture. Of the 122 samples that showed
      abnormal cytology, 81 (66.4%) were positive for HPV. Although the number of
      samples tested is small, the results show that the use of LBC technology for both
      cervical cytological screening and the hybrid capture test has the potential to
      reduce both false-negative and -positive rates associated with cytological
      screening alone.

PMID- 11575743
TI  - Unmasking antigens for immunohistochemistry.
AB  - Preservation of tissue by fixation in a formalin solution, followed by
      dehydration and paraffin-wax embedding remains the predominant method of
      preparation for microscopic analysis of morphology. Whilst this may be optimal
      for morphological assessment, this technique has major disadvantages for
      subsequent immunohistochemical study as a result of the structural alteration of
      antigens that occurs during the processing procedure. However, the introduction
      of a range of antigen unmasking procedures has revolutionised
      immunohistochemistry, establishing the technique as a powerful tool in diagnostic
      pathology. Here, the development of enzymatic, non-enzymatic and heat-based
      antigen retrieval techniques is reviewed, and the methods in use currently are
      appraised.

PMID- 11575744
TI  - Pulmonary aspergillosis: clinical presentation, diagnosis and therapy.
AB  - Pulmonary aspergillosis is a serious threat to those immunocompromised as a
      result of disease or therapy, and has been identified as a major cause of
      morbidity and mortality in asthmatic and cystic fibrosis patients. Pulmonary
      aspergillosis can occur in three principal forms: saprophytic, allergic and
      invasive. Saprophytic aspergillosis involves colonisation of the airways, without
      invasion or damage of viable tissue, and may present as an aspergilloma (fungus
      ball) consisting of a tangled mass of mycelium, fibrin, inflammatory cells and
      epithelial-cell debris. Necrotic tissue also may be invaded but usually only in
      those severely immunocompromised. Allergic aspergillosis is referred to
      frequently as allergic bronchopulmonary aspergillosis (ABPA), and may occur in
      approximately 25% of asthmatic and 10% of cystic fibrosis patients. ABPA presents
      as a non-infectious, potentially fatal inflammatory disease where antigens
      released by the fungal mycelium provoke an immune response. Invasive
      aspergillosis is probably the most serious form of the disease and involves the
      invasion of viable tissue. It occurs predominantly in patients with pre-existing
      lung damage, and can spread to other organs and distant sites in the body.
      Aspergillomas may be detected on chest X-ray as spherical-shaped objects, whilst
      allergic aspergillosis may be visualised by radiological techniques and computed
      tomography (CT) scan. Surgery may be employed in the case of aspergilloma, and
      chemotherapy relies upon the use of amphotericin B (liposomal and aerosolised)
      and itraconazole.

PMID- 11575745
TI  - Occlusal magic..

PMID- 11575746
TI  - Whistle blowing.

PMID- 11575749
TI  - Tracing students.

PMID- 11575750
TI  - Community care.

PMID- 11575751
TI  - Community care.

PMID- 11575752
TI  - Professional flexibility.

PMID- 11575754
TI  - Dental tape--a cautionary tale.

PMID- 11575753
TI  - NHS proposals for change.

PMID- 11575755
TI  - Self-evaluation skills in dentistry.

PMID- 11575757
TI  - Evaluating the training.

PMID- 11575758
TI  - A clinical guide to occlusion: an introduction.

PMID- 11575759
TI  - What is occlusion?
AB  - The aim of this series of papers is to explore the role of occlusion in dental
      practice. The range of opinion in the dental profession as to the importance of
      occlusion is enormous. It is very important that the profession in general and
      practising dentists in particular have a balanced view of occlusion. This is more
      important than every patient having a balanced occlusion. The fact that the study
      of occlusion is characterised by extremes makes it confusing and possibly
      difficult for individual dentists to find a philosophy which is in line with
      contemporary good practice supported by evidence from practice-based research.

PMID- 11575760
TI  - Can audit improve antibiotic prescribing in general dental practice?
AB  - OBJECTIVE: To investigate whether clinical audit can improve general dental
      practitioners' prescribing of antibiotics. DESIGN: An intervention study carried
      out in general dental practice in the North West of England. METHOD: Information
      was collected over an initial six-week period from 175 general dental
      practitioners on their current antibiotic prescribing practices. The information
      collected was the antibiotic prescribed including dose, frequency and duration,
      the clinically presenting signs and conditions, the medical history (if for
      prophylaxis), and any other reasons for prescribing. This was compared to the
      practitioners' antibiotic prescribing for a further six-week period following an
      audit, which included an educational component and the issuing of guidelines.
      RESULTS: During the initial period practitioners issued 2316 prescriptions for
      antibiotics. This was reduced by 42.5% to 1330 during the audit. The majority of
      the antibiotics (81%) for both periods were prescribed for therapeutic reasons.
      The most commonly prescribed antibiotics were amoxycillin (57.6%), metronidazole
      (23.8%), penicillin (9.3%), erythromycin (4.8%) and a combination of amoxycillin
      and metronidazole (1.7%). The antibiotic regimens used by practitioners were
      significantly changed by the audit (P<0.001) and there was a significant
      reduction in the number of prescriptions (P<0.05) which did not conform to
      national guidelines. CONCLUSIONS: The results from this investigation support the
      conclusion that clinical audit, with the issuing of guidelines and an educational
      component, can change prescribing practices leading to a more rational and
      appropriate use of antibiotics in general dental practice.

PMID- 11575761
TI  - Children and informed consent: a study of children's perceptions and involvement
      in consent to dental treatment.
AB  - AIM: The aim of the study was to find out to what extent children are involved in
      consenting to their dental care. METHODS: It was conducted using a structured
      interview with 60 8-13-year-old children. In the control group, verbal consent
      was given by the parent, whilst in the study group written consent was given by
      the parent and verbal assent by the patient. Interviews were conducted after
      dental treatment. RESULTS: The findings indicate that children in the study group
      felt they were more involved in deciding about their dental treatment compared
      with the control group. CONCLUSION: Children want to be more involved in
      consenting to their dental treatment.

PMID- 11575762
TI  - Clinical record keeping by general dental practitioners piloting the Denplan
      'Excel' accreditation programme.
AB  - BACKGROUND: Denplan is a private capitation-based system of providing primary
      dental care in the UK. An additional programme called Denplan Excel has been
      developed which requires General Dental Practitioners to instigate various
      quality processes within their practices in order to become accredited. Clinical
      record keeping is one area where standards are monitored. This study reports
      changes in record keeping at patient recall appointments following the
      implementation of the Denplan Excel programme. METHOD: Fifty dentists
      participating in the Denplan Excel pilot programme from different areas of the UK
      were sampled by means of cluster sampling. Twenty records for each dentist were
      sampled and items recorded for patients recalled both pre- and post-pilot were
      compared. RESULTS: The majority of dentists recorded presenting complaint,
      diagnosis and treatment plan both pre- and post-pilot. However, post-pilot there
      were a number of improvements in record keeping. Caries recorded on a grid
      increased from 7% of records to 46%, basic periodontal examination increased from
      48% to 85% of records and the updating of medical history increased from 51% to
      65% of records. These findings were all significant at the p<0.01 level.
      CONCLUSION: Changes can be achieved by voluntary participation in a system of
      structured record keeping.

PMID- 11575764
TI  - Classification of coordination polygons and polyhedra according to their mode of
      self-assembly.
AB  - This work extends techniques for the controlled formation of synthetic molecular
      containers by metal-mediated self-assembly. A new classification system based on
      the self-assembly of such species is proposed. The system: 1) allows a systematic
      identification of suitable acceptor-donor combinations, 2) widens the variety of
      design possibilities available, 3) allows a ready comparison of the self-assembly
      of different compounds, 4) reveals useful commonalities between different
      compounds, 5) aids in the development of novel architectures, and 6) permits
      identification of systems capable of being switched back-and-forth between
      architectures.

PMID- 11575763
TI  - Experiences and perceptions of vocational training reported by the 1999 cohort of
      vocational dental practitioners and their trainers in England and Wales.
AB  - OBJECTIVE: To assess the self-reported confidence of vocational dental
      practitioners (VDPs) in clinical procedures together with vocational trainers'
      perceptions of the VDPs confidence in the same procedures, immediately after
      qualification and towards the end of the vocational training year. DESIGN: A
      questionnaire-based cohort study. SETTING: A general practice study carried out
      in 1999. SUBJECTS: Vocational Dental Practitioners and vocational trainers in
      England and Wales. METHOD: VDPs and trainers were asked on a single occasion to
      grade the clinical confidence of the VDP at the beginning and near the end of
      vocational training as high, satisfactory or low. RESULTS: Questionnaires were
      sent to 531 VDPs and 555 trainers; 82 per cent of VDPs and trainers responded.
      Approximately half the VDPs were male and 57 per cent were white, whilst 89 per
      cent of trainers were male and 81 per cent white. A large proportion of both VDPs
      and trainers reported low confidence in orthodontics, molar endodontics and
      surgical extractions at the start of the training year. Towards the end of
      training, both groups reported improved confidence levels in most clinical
      procedures. However, a higher proportion of trainers reported low confidence than
      their VDPs in most clinical procedures at both time points (p<0.001). VDPs
      appeared to gain most from experience and training in administration/management
      and interpersonal skills. CONCLUSION: Vocational training appears to satisfy its
      aim to enhance clinical and administrative confidence.

PMID- 11575765
TI  - Rhodium/iridium-titanium azaheterometallocubanes.
AB  - Treatment of [[Ti(eta5-C5Me5)(mu-NH)]3(mu3-N)] (1) with the diolefin complexes
      [[MCl(cod)]2] (M = Rh, Ir; cod = 1,5-cyclooctadiene) in toluene afforded the
      ionic complexes [M-(cod)(mu3-NH)3Ti3(eta5-C5Me5)3(mu3-N)]Cl [M = Rh (2), Ir (3)].
      Reaction of complexes 2 and 3 with [Ag(BPh4)] in dichloromethane leads to anion
      metathesis and formation of the analogous ionic derivatives [M(cod)(mu3-NH)3Ti3
      (eta5-C5Me5)3(mu3-N)][BPh4] [M = Rh (4), Ir (5)]. An X-ray crystal structure
      determination for 5 reveals a cube-type core [IrTi3N4] for the cationic fragment,
      in which 1 coordinates in a tripodal fashion to the iridium atom. Reaction of the
      diolefin complexes [[MCl(cod))2] (M = Rh, Ir) and [[RhCl(C2H4)2]2] with the
      lithium derivative [[Li(mu3-NH)2(mu3-N)-Ti3(eta5-C5Me5)3(mu3-N)]2] x C7H8 (6
      C7H8) in toluene gave the neutral cube-type complexes [M(cod)(mu-NH)2(mu3-N)Ti3
      (eta5-C5Me5)3(mu3-N)] [M = Rh (7), Ir (8)] and [Rh(C2H4)2(mu3-NH)2(mu3-N)Ti3(eta5
      C5Me5)3(mu3-N)] (9), respectively. Density functional theory calculations have
      been carried out on the ionic and neutral azaheterometallocubane complexes to
      understand their electronic structures.

PMID- 11575766
TI  - Trigonal-prismatic versus octahedral molecular structures in [CH3)nMX6-n]]
      compounds.
AB  - The molecular structures of [(CH3)5MoOCH3], [(CH3)4Mo(OCH3)2], [(CH3)5WCl], and
      [(CH3)3WCl(OCH3)2] are reported. The first three structures are based on trigonal
      prismatic geometry, the last one on octahedral geometry.

PMID- 11575767
TI  - Structural variations and bonding in gold halides: a quantum chemical study of
      monomeric and dimeric gold monohalide and gold trihalide molecules, AuX, Au2X2,
      AuX3, and Au2X6 (X = F, Cl, Br, I).
AB  - The molecular structures of all gold mono- and trihalides and of their dimers
      have been calculated at the B3LYP, MP2, and CCSD(T) levels of theory by using
      relativistic pseudopotentials for all atoms except fluorine. Our computations
      support the experimental observation that the relative stability of the
      monohalides increases from the fluoride toward the iodide, while the stability
      trend of the trihalides is the opposite. The potential energy surface (PES) of
      all gold trihalides has been investigated. These molecules are typical Jahn
      Teller systems; the trigonal planar D3h-symmetry geometry does not correspond to
      the minimum energy structure for any of them. At the same time, the amount and
      character of their Jahn-Teller distortion changes gradually from AuF3 to AuI3.
      The minimum energy geometry is a T-shaped structure for AuF3 and AuCl3, with a Y
      shaped transition-state structure. For AuI3, the Y-shaped structure lies lower
      than the T-shaped structure on the PES. For AuBr3 and AuI3, neither of them is
      the global minimum but instead an L-shaped structure, which lies outside the Jahn
      Teller PES. This structure can be considered to be a donor-acceptor system, or a
      closed-shell interaction, with I2 acting as donor and AuI as acceptor. The dimers
      of gold monohalides have very short gold-gold distances and demonstrate the
      aurophilic interaction. The dimers of the trihalides are planar molecules with
      two bridging halogen atoms.

PMID- 11575768
TI  - Novel oxorhenium and oxotechnetium complexes from an aminothiol[NS]/thiol[S]
      mixed-ligand system.
AB  - The simultaneous action of a bidentate aminothiol ligand, LnH, (n = 1:
      (CH3CH2)2NCH2CH2SH and n = 2: C5H10NCH2CH2SH) and a monodentate thiol ligand, LH
      (LH: p-methoxythiophenol) on a suitable MO (M = Re, 99gTc) precursor results in
      the formation of complexes of the general formula [MO(Ln)(L)3] (1, 2 for Re and
      5. 6 for 99gTc). In solution these complexes gradually transform to [MO(Ln)(L)2]
      complexes (3, 4 for Re and 7, 8 for 99gTc). The transformation is much faster for
      oxotechnetium than for oxorhenium complexes. Complexes 1-4, 7, and 8 have been
      isolated and fully characterized by elemental analysis and spectroscopic methods.
      Detailed NMR assignments were made for complexes 3, 4, 7, and 8. X-ray studies
      have demonstrated that the coordination geometry around rhenium in complex 1 is
      square pyramidal (tau = 0.06), with four sulfur atoms (one from the L1H ligand
      and three from three molecules of p-methoxythiophenol) in the basal plane and the
      oxo group in the apical position. The L1H ligand acts as a monodentate ligand
      with the nitrogen atom being protonated and hydrogen bonded to the oxo group. The
      four thiols are deprotonated during complexation resulting in a complex with an
      overall charge of zero. The coordination geometry around rhenium in complex 4 is
      trigonally distorted square pyramidal (tau = 0.41), while in the oxotechnetium
      complex 7 it is square pyramidal (tau = 0.16). In both complexes LnH acts as a
      bidentate ligand. The NS donor atom set of the bidentate ligand and the two
      sulfur atoms of the two monodentate thiols define the basal plane, while the
      oxygen atom occupies the apical position. At the technetium tracer level (99mTc),
      both types of complexes, [99mTcO(Ln)(L)3] and [99mTcO(Ln)(L)2], are formed as
      indicated by HPLC. At high ligand concentrations the major complex is
      [99mTcO(Ln)(L)3], while at low concentrations the predominant complex is
      [99mTcO(Ln)(L)2]. The complexes [99mTcO(Ln)(L)3] transform to the stable
      complexes [99mTcO(Ln)(L)2]. This transformation is much faster in the absence of
      ligands. The complexes [99mTcO(Ln)(L)2] are stable, neutral, and also the
      predominant product of the reaction when low concentrations of ligands are used,
      a fact that is very important from the radiopharmaceutical point of view.

PMID- 11575769
TI  - Reaction mechanism and structure-reactivity relationships in the stereospecific
      1,4-polymerization of butadiene catalyzed by neutral dimeric allylnickel(II)
      halides [Ni(C3H5)X]2 (X- = Cl-, Br-, I-): a comprehensive density functional
      theory study.
AB  - For the first time, a comprehensive and consistent picture of the catalytic cycle
      of 1,4-polymerization of butadiene with neutral dimeric allylnickel(II) halides
      [Ni(C3H5)X]2 (X = Cl- (I), Br- (II), and I- (III)) as single-site catalysts has
      been derived by means of quantum chemical calculations that employ a gradient
      corrected density-functional method. All crucial reaction steps of the entire
      catalytic course have been scrutinized, taking into account butadiene pi complex
      formation, symmetrical and asymmetrical splitting of dimeric pi complexes, cis
      butadiene insertion, and anti-syn isomerization. The present investigation
      examines, in terms of located structures, energies and activation barriers, the
      participation of postulated intermediates, in particular it aimed to clarify
      whether monomeric or dimeric species are the catalytically active species. Prior
      qualitative mechanistic assumptions are substituted by the presented
      theoretically well-founded and detailed analysis of both the thermodynamic and
      the kinetic aspects, that substantially improve the insight into the reaction
      course and enlarge them with novel mechanistic proposals. From a mechanistic
      point of view, all three catalysts exhibit common characteristics. First, chain
      propagation occurs by cis-butadiene insertion into the pi-butenylnickel(II) bond
      with nearly identical intrinsic free-energy activation barriers. Second, the
      reactivity of syn-butenyl forms is distinctly higher than that of anti forms.
      Third, the chain-propagation step is rate-determining in the entire
      polymerization process, and the pre-established anti-syn equilibrium can always
      be regarded as attained. Accordingly, neutral dimeric allylnickel(II) halides
      catalyze the formation of a stereo-regular trans-1,4-polymer under kinetic
      control following the k1t channel with butenyl(halide)(butadiene)NiII complexes
      being the catalytically active species. Production of a stereoregular cis-1,4
      polymer with allylnickel chloride can only be explained by making the k2c channel
      accessible by the formation of polybutadienyl(butadiene) complexes, which is
      accompanied by the coordination of the next double bond in the growing chain to
      the NiII center.

PMID- 11575770
TI  - Oxygen capture by lithiated organozinc reagents containing aromatic 2
      pyridylamide ligands.
AB  - The sequential reaction of ZnMe2 with a 2-pyridylamine (HN(2-C5H4N)R, R = Ph: 1;
      3,5-Xy (=3,5-xylyl): 2; 2,6-Xy: 3; Bz (=benzyl): 4; Me: 5), tBuLi and thereafter
      with oxygen affords various lithium zincate species, the solid-state structures
      of which reveal a diversity of oxo-capture modes. Amine 1 reacts to give both
      dimeric THF [Li(Me)OZn[N(2-C5H4N)Ph]2] (6), wherein oxygen has inserted into the
      Zn-C bond of a [MeZn[N(2-C5H4N)-Ph]2] ion, and the trigonal Li2Zn complex,
      bis(OtBu)-capped (THF x Li)2-[[(mu3-O)tBu]2Zn[N(2-C5H4N)Ph]2] (7). The structural
      analogue of 6 (8) results from the employment of 2, while the use of more
      sterically congested 3 yields a pseudo-cubane dimer [(THF x
      [Li(tBu)OZn(OtBu)Me]]2] (9) notable for the retention of labile Zn-C(Me). Amines
      4 and 5 afford the oxo-encapsulation products [mu4-O)Zn4[(2-C5H4N)-NBz]6] (10b),
      and [tBu(mu3-O)-Li3(mu6-O)Zn3[(2-C5H4N)NMe]6] (11), respectively, with
      concomitant oxo-insertion into a Li-C interaction resulting in capping of the fac
      isomeric (mu6-O)M3M'3 distorted octahedral core of the latter complex by a tert
      butoxide group.

PMID- 11575771
TI  - Characterisation of zeolitic materials with a HEU-type structure modified by
      transition metal elements: definition of acid sites in nickel-loaded crystals in
      the light of experimental and quantum-chemical results.
AB  - Nickel-loaded HEU-type zeolite crystals have been obtained by well-known
      synthetic procedures and characterised by X-ray fluorescence (XRF), scanning
      electron microscopy/ energy-dispersive spectroscopy (SEM-EDS), FT-IR, diffuse
      reflectance UV/ Vis spectroscopy (DR(UV/Vis)S) and X-ray photoelectron
      spectroscopy (XPS) measurements as non-homoionic and non-stoichiometric
      substances containing exchangeable hydrated Ni2+ ions in the micropores and
      nickel hydroxide phases supported on the surface. Thermogravimetric
      analysis/differential gravimetry (TGA/DTG) and differential thermal analysis
      (DTA) demonstrated that full dehydration below approximately 400 degrees C
      follows a clearly endothermic process, whereas at higher temperatures the zeolite
      is amorphised and finally partially recrystallised to Ni(Al,Si) oxides, detected
      by powder X-ray powder diffraction (XRD). The solid acidity of NiHEU, initially
      determined by temperature-programmed desorption (TPD) of ammonia to be 8.93 mgg(
      1) NH3, is attributed to the weak acid sites (fundamentally Lewis sites) resolved
      at approximately 183 degrees C, and to the strong acid sites (essentially
      Bronsted sites) resolved at approximately 461 degrees C in the TPD pattern. A
      more sophisticated study based on in situ/ex situ FT-IR with in situ/ex situ 27Al
      MAS NMR and pyridine (Py) as a probe molecule, revealed that the Lewis acid sites
      can be attributed primarily to Ni2+ ions, whereas the Bronsted ones can probably
      be associated with the surface-supported nickel hydroxide phases. The
      spectroscopic measurements in conjunction with powder XRD and 29Si MAS NMR data
      strongly suggest that distorted Al tetrahedra are formed during the dehydration
      process and Py chemisorption/complexation (NiHEU-Py), whereas the crystal
      structure is remarkably well preserved in the rehydrated material (NiHEU-Py/R).
      The structural, electronic, energetic and spectroscopic properties of all
      possible nickel(II) aqua and dihydroxy complexes absorbed in the zeolite
      micropores or supported on the zeolite surface were studied theoretically by
      density functional theory (DFT). The computed proton affinity, found to be in the
      range 182.0-210.0 kcalmol(-1), increases with increasing coordination number of
      the aqua and dihydroxy nickel(II) complexes.

PMID- 11575772
TI  - Cationic host-guest polymerization of N-vinylcarbazole and vinyl ethers in MCM
      41, MCM-48, and nanoporous glasses.
AB  - The synthesis of poly(vinyl ether)s or polyvinylcarbazole under the conditions of
      constricted geometry can be achieved by means of cationic host-guest
      polymerisation of the corresponding monomers in the pores of MCM-41 (pore
      diameter 3.6 nm), MCM-48 (pore diameter 2.4 nm) and in nanoporous glasses (Gelsil
      with a pore diameter of 5 nm) with bis(4-methoxyphenyl)methyl chloride (BMCC) or
      triphenylmethyl chloride as the internal surface initiator. The reaction products
      are new polymer/ MCM-41, polymer/MCM-48 etc., host-guest hybrid materials. The
      molecular mass of the enclosed polymer and the degree of loading of the host
      compounds can be adjusted within certain limits. The molecular dynamics were
      investigated by using broad-band dielectric spectroscopy. Under the conditions of
      constricted geometry, molecular fluctuation is observed as well as a secondary
      beta-relaxation, which is hardly affected (in comparison with the free melt) and
      which corresponds to the relaxation between structural substates (dynamic glass
      transition). This process is several orders of magnitude faster in its relaxation
      rate than in the free melt and thus follows a confinement effect. This is already
      well known in lower molecular weight systems with constricted geometry.

PMID- 11575774
TI  - Dipolar donor-acceptor-substituted schiff base complexes with large off-diagonal
      second-order nonlinear optical tensor components.
AB  - The synthesis, characterization, and two-dimensional second-order nonlinear
      optical (NLO) response of a dipolar NiII donor- acceptor Schiff base complex and
      the related ligand are reported. Electric-field-induced second-harmonic
      generation and harmonic light (hyper-Rayleigh) scattering techniques, in
      combination with INDO/SCI-SOS theoretical calculations, were used to investigate
      the vector part of the hyperpolarizability tensor and the two-dimensional
      character of the molecular nonlinearity, respectively. Off-diagonal
      hyperpolarizability tensors can be related to charge-transfer transitions that
      are polarized perpendicular to the molecular dipolar axis, while parallel
      transitions account for the diagonal hyperpolarizability tensor. The role of the
      metal center in enhancing the two-dimensional NLO response of such molecules is
      twofold since it acts both as the donor and the bridging moiety of the planar
      donor-(pi-conjugate-bridge)-acceptor system. These dipolar two-dimensional
      molecules are interesting candidates from the perspective of polarization
      independent NLO materials.

PMID- 11575773
TI  - Stabilities and isomeric equilibria in solutions of monomeric metal-ion complexes
      of guanosine 5'-triphosphate (GTP4-) and inosine 5'-triphosphate (ITP4-) in
      comparison with those of adenosine 5'-triphosphate (ATP4-).
AB  - Under experimental conditions in which the self-association of the purine
      nucleoside 5'-triphosphates (PuNTPs) GTP and ITP is negligible, potentiometric pH
      titrations were carried out to determine the stabilities of the M(H;PuNTP) and
      M(PuNTP)2-complexes where M2+ = Mg2+, Ca2+, Sr2+. Ba2+, Mn2+, Co2+, Ni2+, Cu2+,
      Zn2+, or Cd2+ (I = 0.1 M, 25 degrees C). The stabilities of all M(GTP)2- and
      M(ITP)2- complexes are significantly larger than those of the corresponding
      complexes formed with pyrimidine-nucleoside 5'-triphosphates (PyNTPs), which had
      been determined previously under the same conditions. This increased complex
      stability is attributed, in agreement with previous 1H MNR shift studies, to the
      formation of macrochelates of the phosphate-coordinated metal ions with N7 of the
      purine residues. A similar enhanced stability (despite relatively large error
      limits) was observed for the M(H;PuNTP) complexes, in which H+ is bound to the
      terminal y-phosphate group, relative to the stability of the M(H;PyNTP)- species.
      The percentage of the macrochelated isomers in the M(GTP)2- and M(ITP)2- systems
      was quantified by employing the difference log KMM(PuNTP)-log KMM(PyNTP); the
      lowest and highest formation degrees of the macrochelates were observed for
      Mg(ITP)2- and Cu(GTP)2- with 17 +/- 11% and 97 +/- 1%, respectively. From
      previous studies of M(ATP)2- complexes, it is known that innersphere and
      outersphere macrochelates may form; that is, in the latter case a water molecule
      is between N7 and the phosphate-coordinated M2+. Similar conclusions are reached
      now by comparisons with earlier 1H MNR shift measurements, that is, that Mg(GTP)2
      (21 +/- 11%), for example, exists largely in the form of an outersphere
      macrochelate and Zn(GTP)2- (68 +/- 4%) as an innersphere one. Generally, the
      overall percentage of macrochelate falls off for a given metal ion in the order
      M(GTP)2- > M(ITP)2- > M(ATP)2-; this is in accord with the decreasing basicity of
      N7 and the steric inhibition of the (C6)NH2 group in the adenine residue.
      Furthermore, although the absolute stability constants of the previously studied
      M(GMP), M(IMP), and M(AMP) complexes differ by about two to three log units from
      the present M(PuNTP)2- results, the formation degrees of the macrochelates are
      astonishingly similar for the two series of nucleotides for a given metal ion and
      purine-nucleobase residue. The conclusion that N7 of the guanine residue is an
      especially favored binding site for metal ions is also in accord with
      observations made for nucleic acids.

PMID- 11575775
TI  - Efficient synthesis of isofagomine and noeuromycin.
AB  - Starting from D-arabinose the synthesis of the very strong glycosidase inhibitors
      isofagomine (2) and noeuromycin (3) was achieved in six and seven steps,
      respectively. Keystep in the reaction sequence is the application of an efficient
      C-4 oxidation method to benzyl alpha-D-arabino-pyranoside. Subsequent Henry
      reaction of the obtained aldoketose with nitromethane provided the required
      branched carbohydrate precursors, which gave access to 2 and 3 in 17-21% overall
      yield.

PMID- 11575776
TI  - Catalytic antibodies induced by a zwitterionic hapten.
AB  - A zwitterionic hapten 4 featuring both positively and negatively charged
      functional groups was designed and synthesized with the goal of generating
      catalytic antibodies for the hydrolysis of ester 6 and amide 7. Of the 36
      monoclonal antibodies specific to BSA-4 (bovine serum albumin) that were
      isolated, six accelerated the hydrolysis of 6. Two catalytic antibodies with
      distinctively different and representative kinetic behaviors were selected for
      detailed kinetic studies. Whereas H8-2-6F11 showed burst kinetic behavior, which
      can be attributed to the formation of an acyl intermediate, H8-1-2D5 did not, but
      it did exhibit high multiple turnover activity. The rate of hydrolysis of 6
      catalyzed by H8-1-2D5 followed Michaelis-Menten kinetics; the apparent values of
      the Michaelis-Menten constant Km and the catalytic constant kcat were 488 microM
      and 3.5 min(-1), respectively. The catalytic rate enhancement (kcat/kun) observed
      for H8-1-2D5 was 1.3 x 10(5), which is approximately two orders of magnitude
      greater than those for monofunctional haptens. Thus H8-1-2D5 compares well in
      catalytic activity with antibodies isolated by a related approach called
      heterologous immunization.

PMID- 11575777
TI  - The charge density distribution in a model compound of the catalytic triad in
      serine proteases.
AB  - Combined low temperature (28(1) K) X-ray and neutron diffraction measurements
      were carried out on the co-crystallised complex of betaine, imidazole, and picric
      acid (1). The experimental charge density was determined and compared with ab
      initio theoretical calculations at the B3LYP/6-311G(d,p) level of theory. The
      complex serves as a model for the active site in, for example, the serine
      protease class of enzymes, the so-called catalytic triad. The crystal contains
      three short strong N-H...O hydrogen bonds (HBs) with dN...O < 2.7 A. The three
      HBs have energies above 13 kcalmol(-1), although the hydrogen atoms are firmly
      localized in the "nitrogen wells". This suggests that low-barrier hydrogen
      bonding in catalytic enzyme reactions may be a sufficient, but not a necessary,
      condition for obtaining transition-state stabilization. Structural analysis
      (e.g., covalent N-H bond lengthening) indicates that the hydrogen bond between
      H3A and 08 of imidazole and betaine respectively (HB2) is slightly stronger than
      the bond between H1A and O1A of imidazole and picric acid (HB1), although HB1 is
      shorter than HB2: (dN...O(HB1)= 2.614(1) A, dN...O(HB2) = 2.684(1) A, dH...O(HB1)
      = 1.630(1) A, dH...O(HB2)= 1.635(1) A, dN-H(HB1) = 1.046(1) A, dN-H(HB2) =
      1.057(1) A). Furthermore, the charge density analysis reveals that HB2 has a
      larger covalent character than HB1, with considerable polarization of the density
      towards the acceptor atom. The Gatti and Bader source function (S) is introduced
      to the analysis of strong HBs. The source function is found to be a sensitive
      measure for the nature of a hydrogen bond, and comparison with low-barrier and
      single-well hydrogen bonding systems (e.g., benzoylacetone and nitromalonamide)
      shows that the low-barrier hydrogen bond (LBHB) state is characterized by an
      enormously increased hydrogen atom source contribution to the bond critical point
      in the HB. In this context, HB2 can be characterized as intermediate between
      localized HBs and delocalized LBHBs.

PMID- 11575778
TI  - AAA in KAT/DYKAT processes: first- and second-generation asymmetric syntheses of
      (+)- and (-)-cyclophellitol.
AB  - Kinetic resolutions and kinetic asymmetric transformations (KAT) as well as
      dynamic kinetic resolutions and dynamic kinetic asymmetric transformations
      (DYKAT) are important synthetic protocols. The feasibility of KAT and DYKAT
      processes for asymmetric allylic alkylations (AAA) is explored utilizing a single
      substrate--conduritol B tetraesters. Both processes can be performed resulting in
      excellent enantioselectivity. The impact of nucleophile and leaving group on the
      effectiveness of each is outlined. The ability to differentiate the various
      hydroxyl groups is also described. For this purpose, 4-tert-butyldimethylsiloxy
      2,2-dimethylbutyric acid was developed as a nucleophile. The utility of effecting
      KAT/DYKAT processes through the Pd-catalyzed AAA reaction is demonstrated by
      efficient syntheses of both enantiomers of the potent glycosidase inhibitor
      cyclophellitol.

PMID- 11575779
TI  - Asymmetric epoxidation with a photoactivated [Ru(salen)] complex.
AB  - (Nitrosyl)(salen)ruthenium(II) complex 1 was found to serve as an efficient
      catalyst for the epoxidation of conjugated olefins under photoirradiation, with
      2,6-dichloropyridine N-oxide (2) or tetramethylpyrazine N,N'-dioxide as a
      stoichiometric oxidant. High enantioselectivity was achieved irrespective of the
      substitution pattern of olefins. The choice of solvent depends on stability of
      the resulting epoxides: high enantioselectivity is generally observed in the
      reaction with ethereal solvents, but use of benzene is recommended when the
      resulting epoxides are acid-sensitive.

PMID- 11575780
TI  - Crown compounds for anions: sandwich and half-sandwich complexes of cyclic
      trimetric perfluoro-o-phenylenemercury with polyhedral closo-[B10H10]2- and closo
      [B12H12]2- anions.
AB  - It has been shown by IR and NMR spectroscopy that cyclic trimeric perfluoro-o
      phenylenemercury (o-C6F4-Hg)3 (1) is capable of binding closo-[B10H10]2- and
      closo-[B12H12]2- anions to form complexes [[(o-C6F4Hg)3](B10-H10)]2- (2), [[(o
      C6F4Hg)3]2(B10H10)]2-(3), [[(o-C6F4Hg)3](B12H12)]2- (4), and [[(o
      C6F4Hg)3]2(B12H12)]2- (5). According to IR data, the bonding of the [B10H10]2-
      and [B12H12]2- ions to the macrocycle in these complexes is accomplished through
      the formation of B-H-Hg bridges. Complexes 2, 3, and 5 have been isolated in
      analytically pure form and have been characterized by spectroscopic means. X-ray
      diffraction studies of 3 and 5 have revealed that these compounds have unusual
      sandwich structures, in which the polyhedral di-anion is located between the
      planes of two molecules of 1 and is bonded to each of them through two types of B
      H-Hg bridges. One type is the simultaneous coordination of a B-H group to all
      three Hg atoms of the macrocycle. The other type is the coordination of a B-H
      group to a single Hg atom of the cycle. According to X-ray diffraction data,
      complex 2 has an analogous but half-sandwich structure. The obtained complexes 2
      5 are quite stable; their stability constants in THF/acetone (1:1) at 20 degrees
      C have been determined as 1.0 x 10(2)Lmol(-1), 2.6 x 10(3)L(2)mol(2), 0.7 x
      10(2)Lmol(-1), and 0.98 x 10(3)L(2)mol(-2), respectively.

PMID- 11575781
TI  - Organometallic supramolecular chemistry with monosaccharides: triethylammonium mu
      chloro-bis[chloro(eta5-cyclopentadienyl)-(methyl 4,6-o-benzylidene-beta-D
      glucopyranosidato-1kappaO2,1:2kappaO3) zirconate].
AB  - The reaction of [CpZrCl3(thf)2] with methyl 4,6-O-benzylidene-beta-D
      glucopyranoside (beta-MeBGH2, 1) in the presence of Et3N results in the formation
      of the zirconate complex [Et3NH] [(CpZrCl)2(mu-Cl) (mu-(beta-MeBG)]2] (2). X-ray
      structure analyses were performed from the ligand precursor beta-MeBGH2 1 as well
      as from 2. Compound 1 crystallizes in the monoclinic chiral space group P2(1).
      The molecules show a flat arrangement including the benzylidene protecting group,
      and are packed in columns. The columns are held together in pairs by the
      formation of hydrogen bonds between the hydroxy functions in positions 2 and 3.
      Compound 2 crystallizes in the orthorhombic space group P2(1)2(1)2(1). The beta
      MeBG ligands are chelating the Zr atoms through the oxygen atoms in positions 2
      and 3 of the glucopyranosidato ligand revealing a 1-zircona-2,5-dioxolane moiety
      each; the oxygen atom in position 3 is linked to both of the Zr atoms.
      Additionally one chloro ligand is bridging the two Zr centers. Two terminally
      bound chloro ligands stick out from the two Zr atoms into a chiral U-shaped
      cavity constructed by the two beta-MeBG ligands. The cavity incorporates the
      tertiary ammonium cation [Et3NH]+ which is bound to one of the terminal chloro
      ligands through a hydrogen bond. The inclusion of the [Et3NH]+ cation in the U
      shaped cavity, even in solution, is demonstrated by NMR spectroscopic data.

PMID- 11575782
TI  - Solid- and solution-phase synthesis of vancomycin and vancomycin analogues with
      activity against vancomycin-resistant bacteria.
AB  - Vancomycin, the prototypical member of the glycopeptide family of antibiotics, is
      a clinically used antibiotic employed against a variety of drug-resistant
      bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA).
      The recent emergence of vancomycin resistance, viewed as a growing threat to
      public health, prompted us to initiate a program aimed at restoring the potency
      of this important antibiotic through chemical manipulation of the vancomycin
      structure. Herein, we describe the development of synthetic technology based on
      the design of a novel selenium safety catch linker, application of this
      technology to a solid-phase semisynthesis of vancomycin, and the solid- and
      solution-phase synthesis of vancomycin libraries. Biological evaluation of these
      compound libraries led to the identification of a number of in vitro highly
      potent antibacterial agents effective against vancomycin-resistant bacteria. In
      addition to aiding these investigations, the solid-phase chemistry described
      herein is expected to enhance the power of combinatorial chemistry and facilitate
      chemical biology and medicinal chemistry studies.

PMID- 11575783
TI  - Synthesis and biological evaluation of vancomycin dimers with potent activity
      against vancomycin-resistant bacteria: target-accelerated combinatorial
      synthesis.
AB  - Based on the notion that dimerization and/or variation of amino acid 1 of
      vancomycin could potentially enhance biological activity, a series of synthetic
      and chemical biology studies were undertaken in order to discover potent
      antibacterial agents. Herein we describe two ligation methods (disulfide
      formation and olefin metathesis) for dimerizing vancomycin derivatives and
      applications of target-accelerated combinatorial synthesis (e.g. combinatorial
      synthesis in the presence of vancomycin's target Ac2-L-Lys-D-Ala-D-Ala) to
      generate libraries of vancomycin dimers. Screening of these compound libraries
      led to the identification of a number of highly potent antibiotics effective
      against vancomycin-suspectible, vancomycin-intermediate resistant and, most
      significantly, vancomycin-resistant bacteria.

PMID- 11575784
TI  - High-speed GC and GC/time-of-flight MS of lemon and lime oil samples.
AB  - The high-speed GC separation and MS characterization of lime oil and lemon oil
      samples using programmable column selectivity and time-of-flight mass
      spectrometry is described. The volatile essential oils are separated on a series
      coupled (tandem) column ensemble consisting of a polar trifluoropropylmethyl
      polysiloxane column and a nonpolar 5% phenyl dimethyl polysiloxane column. Both
      columns are 7 m long. A 50 degrees C/min linear temperature ramp from 50 to 200
      degrees C is used, giving an analysis time of approximately 2.5 min. A time-of
      flight MS with time array detection and automated peak finding and
      characterization software was used to identify 50 components in lime oil samples
      and 25 components in lemon oil samples. Despite numerous cases of extensive peak
      overlap, spectral deconvolution software was very successful in the
      characterization of most overlapping peaks. For cases where a more complete
      chromatographic separation is desirable, the tandem column ensemble is operated
      in the first-column stop-flow mode to enhance the separation of selected
      overlapping clusters of peaks. A valve between the junction point of the tandem
      column ensemble and a source of carrier gas at the GC inlet pressure is opened
      for 2-5-s intervals to stop the flow of carrier gas in the first column. This is
      used to increase the separation of target component groups that overlap in the
      ensemble chromatogram without first-column stop-flow operation. This procedure is
      used to isolate the peak for limonene, the largest peak in the analytical-ion
      chromatogram of both the lime and lemon oil samples.

PMID- 11575785
TI  - Study of the hydrolysis of a sulfonylurea herbicide using liquid chromatography
      with diode array detection and mass spectrometry by three-way multivariate curve
      resolution-alternating least squares.
AB  - This research is focused on the development of a novel, automated chemometric
      method for obtaining relevant chemical information from time-course measurements
      of an evolving chemical system. This paper describes an investigation of the
      hydrolysis of Ally, which is a sulfonylurea herbicide. The hydrolysis of this
      compound is observed at different pHs and temperatures by reversed-phase liquid
      chromatography using a diode array detector. The data are analyzed using a three
      way, multivariate curve resolution technique. Of special interest was the
      application of a closure constraint in the kinetic dimension followed by the
      determination of the rate constants for each step of the pathway by using a
      differential equation solver and nonlinear fitting of the data.

PMID- 11575786
TI  - Application of solid-phase microextraction in the determination of diazepam
      binding to human serum albumin.
AB  - In this paper, protein-drug interactions were studied by solid-phase
      microextraction (SPME) using diazepam binding to human serum albumin as a model
      system. Since drug compounds are normally polar and nonvolatile by nature, direct
      SPME is used in this work. The SPME extraction is an equilibrium process among
      the concentrations of the analyte partitioned onto the SPME fiber, free and bound
      drug in the solution. A calibration curve was first constructed by employing the
      amount of the analytes partitioned on the fiber versus the free analyte
      concentration in the solution in the absence of protein. In method I, the
      extraction was performed in the protein solution with known diazepam
      concentration. In method II, diazepam was first loaded onto the fiber by
      extracting in solution with known diazepam concentration. This fiber was
      subsequently transferred into the protein solution for desorption. The amount of
      the analyte left on the fiber was analyzed after the system reached equilibrium.
      The free drug concentration was then obtained from the calibration curve for both
      methods. The Scatchard plot was finally employed to obtain the number of binding
      sites and the equilibrium binding constants. Since only a very small amount of
      the protein solution is required (150 microL for each extraction), method II is
      very useful for circumstances where the protein amount is very limited. The
      direct measurement method proposed in this paper does not need a GC response
      factor, which significantly decreases the experimental error. The only
      measurement needed is the area count change (ratio) of the fiber injections
      before and after the protein was introduced into the solution. The difference
      between the direct measurement method for method I and method II is discussed.
      The result illustrated that the SPME direct measurement method provided both
      theoretical accuracy and simplicity in such applications.

PMID- 11575787
TI  - Development of tunable picosecond dye laser for multiphoton ionization of dioxin
      precursors in supersonic jet/time-of-flight mass spectrometry.
AB  - A distributed-feedback dye laser has been developed for achieving the efficient
      multiphoton ionization of chlorobenzene and dichlorobenzene, that is, precursor
      molecules of dioxins. This tunable picosecond laser with a narrow spectral line
      width, that is, a nearly transform-limited pulse, provides a more efficient
      ionization than the nanosecond laser, which is currently in use in supersonic jet
      spectrometry. The advantage of picosecond over nanosecond and femtosecond lasers
      is also discussed on the basis of the theoretical model reported in a previous
      paper.

PMID- 11575788
TI  - A method for the quantitative analysis of iron speciation in meat by using a
      combination of spectrophotometric methods and high-performance liquid
      chromatography coupled to sector field inductively coupled plasma mass
      spectrometry.
AB  - The determination of the heme and non-heme iron fractions in raw and cooked beef
      steak by using spectrophotometric methods and high-performance liquid
      chromatography coupled to a double-focusing sector field inductively coupled
      plasma mass spectrometer (HPLC-SF-ICPMS) is reported. Size exclusion
      chromatography coupled to SF-ICPMS was used to measure the iron-containing
      biomolecules in the samples. This approach allowed for the direct on-line
      detection of the most abundant iron isotope 56Fe without interference from
      40Ar16O. The HPLC-ICPMS results for the iron speciation analysis of a raw beef
      steak, used as an analytical quality control (AQC) sample, showed that the main
      iron biomolecule present was the heme iron-containing protein myoglobin. For the
      AQC sample, the agreement among the HPLC-ICPMS method, the non-heme iron
      spectrophotometric method, and the total iron concentration showed 100% recovery
      of iron. The sum of the different iron-containing compounds determined using the
      developed HPLC-ICPMS method accounted for all the iron-containing compounds
      extracted. The analysis of myoglobin in steak by HPLC-ICPMS showed that on
      cooking the concentration was reduced by 85%. However, a spectrophotometric
      method specific for heme iron showed that it was still intact, even after heating
      to 80 degrees C. The measurement of the total iron in the cooked steak and the
      HPLC extracts by inductively coupled plasma optical emission spectroscopy (ICP
      OES) indicated that the extraction method for the HPLC analysis was no longer
      applicable and that loss of the heme group from the protein rendered it
      incompatible with the size exclusion separation. The detection limit
      (concentration equivalent to 3 times the baseline for a blank injection) of the
      HPLC-ICPMS method was 2.4 ng as iron. The results demonstrate that a combination
      of analytical methods can be used to provide valuable information about dietary
      levels of nutritionally important metal-containing compounds as well as the
      efficiency of established extraction methods for raw and cooked meat samples.

PMID- 11575789
TI  - Nonaqueous catalytic fluorometric trace determination of vanadium based on the
      pyronine B-hydrogen peroxide reaction and flow injection after cloud point
      extraction.
AB  - The catalytic effect of vanadium on the pyronine B-H2O2 system is examined.
      Enhancement of the catalytic reaction rate along with the efficiency and
      selectivity against vanadium is achieved in a formic acid environment in the
      presence of a nonionic surfactant (Triton X-114). Elimination of drastic
      interference caused by inorganic acids and aqueous matrix along with a 50-fold
      preconcentration of vanadium are facilitated through cloud point extraction of
      its neutral complex with 8-quinolinol in an acidic solution. Subsequent flow
      injection analysis (FIA) with fluorometric detection renders the proposed method
      ideal for selective and cost-effective determination of as little as 0.020
      microng L(-1) vanadium in environmental, biological, and food substrates. The
      preconcentration step can be applied simultaneously to multiple samples, allowing
      for massive preparation prior to analysis, compensating, thus, for the time
      consuming procedure.

PMID- 11575790
TI  - Combinatorial screening of heterogeneous catalysis in selective oxidation of
      naphthalene by laser-induced fluorescence imaging.
AB  - Heterogeneous catalysis is one of the most important processes in the petroleum
      and the chemical industries. To be able to screen catalysts at high throughput
      will dramatically improve performance and reduce costs. Here we used laser
      induced fluorescence imaging as a high-throughput screening technique in the
      combinatorial discovery of active catalysts for naphthalene oxidation. Binary
      catalysts of V-Mo-O, V-Sn-O, V-Ti-O, and V-W-O in various 15-member libraries
      were screened. Laser ablation ICPMS was employed to confirm the composition of
      the individual catalysts in the combinatorial library. The addition of MoO3, WO3,
      SnO2, and TiO2 to V2O5 did not improve the catalytic activity in the conversion
      of naphthalene to naphthoquinone, but the overall activity was found to increase
      for certain binary samples. The screening of ternary catalysts of V-Sn-Mo-O
      revealed that the combination of V (45%)-Sn (45%)-Mo (10%) gave 70% higher
      catalytic activity than pure V2O5 in converting naphthalene to naphthoquinone.
      Reaction temperature and sample preparation effects on the activity and
      selectivity of catalysts are also studied in a combinatorial manner.

PMID- 11575791
TI  - Core-shell nanostructured nanoparticle films as chemically sensitive interfaces.
AB  - This paper reports the results of an investigation of vapor molecule sorption at
      different types of nanostructured nanoparticle films. Core-shell nanoparticles of
      two different core sizes, AU2-nm and Au5-nm, and molecular linkers of two
      different binding properties, 1,9-nonanedithiol and 11-mercaptoundecanoic acid,
      are utilized as building blocks for constructing chemically sensitive interfaces.
      The work couples measurements of two different transducers, interdigitated
      microelectrodes and quartz crystal microbalance, to determine the correlation of
      the electronic resistance change and the mass loading with vapor sorption. The
      responses to vapor sorption at these nanostructured interfaces are demonstrated
      to be dependent on the core size of nanoparticles and the chemical nature of
      linking molecules. The difference of molecular interactions of vapor molecules at
      the nanostructured interface is shown to have a significant impact on the
      response profile and sensitivity. For the tested vapor molecules, while there are
      small differences for the sorption of nonpolar and hydrophobic vapor molecules,
      there are striking differences for the sorption of polar and hydrophilic vapor
      molecules at these nanostructured interfacial materials. The implication of the
      findings to the delineation of design parameters for constructing core-shell
      nanoparticle assemblies as chemically sensitive interfacial materials is also
      discussed.

PMID- 11575792
TI  - Gold nanoparticle-based quantitative electrochemical detection of amplified human
      cytomegalovirus DNA using disposable microband electrodes.
AB  - An electrochemical DNA detection method has been developed for the sensitive
      quantification of an amplified 406-base pair human cytomegalovirus DNA sequence
      (HCMV DNA). The assay relies on (i) the hybridization of the single-stranded
      target HCMV DNA with an oligonucleotide-modified Au nanoparticle probe, (ii)
      followed by the release of the gold metal atoms anchored on the hybrids by
      oxidative metal dissolution, and (iii) the indirect determination of the
      solubilized AuIII ions by anodic stripping voltammetry at a sandwich-type screen
      printed microband electrode (SPMBE). Due to the enhancement of the AuIII mass
      transfer by nonlinear diffusion during the electrodeposition time, the SPMBE
      allows the sensitive determination of AuIII in a small volume of quiescent
      solution. The combination of the sensitive AuIII determination at a SPMBE with
      the large number of AuIII released from each gold nanoparticle probe allows
      detection of as low as 5 pM amplified HCMV DNA fragment.

PMID- 11575793
TI  - Sulfur and oxygen isotope analysis of sulfate at micromole levels using a
      pyrolysis technique in a continuous flow system.
AB  - The discovery of a mass-independent isotopic composition (delta17O = (delta17O -
      0.512 * delta18O) no equal to 0) in aerosol sulfate and the identification of its
      origin (aqueous-phase oxidation by 03 and H2O2) have renewed interest in
      measuring the oxygen isotopic content of sulfate. In this paper, we present a new
      method to measure both delta17O and delta18O in SO4, with the possibility of
      sulfur isotope analysis on the same sample. The technique takes advantage of the
      easy pyrolysis of Ag2SO4 to SO2, O2, and Ag metal in a continuous flow system.
      Because the technique is not quantitative in oxygen (yield approximately 45% for
      O2), a calibration is needed. Correction factors of +0.87 and +0.44% were
      obtained for delta18O and delta17O, respectively. A technique to convert
      micromole levels of sulfate in any form to silver sulfate is described. To reach
      this goal, a solid electrolyte (Nafion membrane) is used in an electrolysis
      apparatus. Reproducibilities for micromole sample sizes are (1sigma) 0.5, 0.3,
      and 0.1% for delta18O, delta17O, and delta17O, respectively. No memory effects or
      isotopic exchange during the treatment of the sample is observed. The main
      advantages of this new method over the existing ones are no fluorinating agent is
      needed, both oxygen and sulfur isotopes can be measured on the same sample, only
      very small amounts of sulfate are needed (down to 100 microg (1 micromol)), it is
      relatively fast and inexpensive, and the possibility exists to couple this
      technique to an on-line analysis.

PMID- 11575794
TI  - Electrochemical evaluation of the interfacial capacitance upon phosphorylation of
      amino acid analogue molecular films.
AB  - An approach based on electrochemistry to differentiate between phosphorylated and
      nonphosphorylated amino acid analogues adsorbed on gold is presented. Analogues
      of serine, threonine, and tyrosine, containing thiohexadecyl headgroups, were
      synthesized and assembled on gold, and the surface capacitance was evaluated
      using electrochemical impedance spectroscopy. A procedure for deprotection of
      tert-butyl phosphate protecting groups, on the monolayer, is also described.
      Characterizations of the assembled analogues by cyclic voltammetry, infrared
      spectroscopy, and ellipsometry are used to confirm the insulating properties of
      the monolayers and the outcome of surface modifications. The results from cyclic
      voltammetry show good insulating properties for the monolayers even after
      phosphate deprotection. The infrared measurements reveal well-ordered monolayers,
      and the thickness from ellipsometry is in good agreement with expectations from
      molecular modeling. The impedance experiments show a capacitance increase up to
      0.6 microF/cm2 as phosphate groups are introduced. The results in this study
      indicate the possibility of using a surface chemical and impedance spectroscopy
      approach to detect the kinase/phosphatase activity and kinetics involved in
      phosphorylation reactions.

PMID- 11575795
TI  - Electroporation of single cells and tissues with an electrolyte-filled capillary.
AB  - We show how an electrolyte-filled capillary (EFC) coupled to a high-voltage power
      supply can be used as a versatile electroporation tool for the delivery of dyes,
      drugs, and biomolecules to the cytoplasm of single cells and cells in tissues. A
      large-voltage pulse applied across the EFC (fused silica, 30 cm long, 375-microm
      o.d., 30-microm i.d.) gives rise to a small electric field outside the terminus
      of the EFC, which causes pore formation in cell membranes and induces an
      electroosmotic flow of electrolyte. When the EFC contains cell-loading agents,
      then the electroosmotic flow delivers the agents at the site of pore formation.
      The combination of pore formation and delivery enables loading of materials into
      the cytoplasm. By patch-clamp and fluorescence microscopy, formation of pores was
      observed at estimated transmembrane voltages of <85 mV with half-maximum values
      around 206 mV. The electroporation protocol was demonstrated by introduction of
      fluorogenic dyes into single NG108-15 cells, cellular processes, and small
      populations of cells in organotypic hippocampal cultures. Preliminary results are
      shown in which this protocol was employed for in vivo electroporation of ventral
      mesencephalon in rat brains. The technique was also used to access organelle
      based detection systems inside cells. As a demonstration, 1,4,5
      inositoltriphosphate was added to the electrolyte and detected by intracellular
      organelles in electroporated cells.

PMID- 11575796
TI  - Separation of selected basic pharmaceuticals by reversed-phase and ion-exchange
      chromatography using thermally tuned tandem columns.
AB  - The separation of basic pharmaceuticals is usually performed on C8 or C18 bonded
      silica supports. Silanolphilic interactions between basic analytes and surface
      silanol groups often lead to tailed peaks, poor efficiency, and irreproducible
      retention times. To solve these problems, many new types of silica-, zirconia-,
      and polymer-based columns, which provide unique selectivities, improved stability
      at high pH, or both, have been developed for the analysis of basic compounds. The
      essence of method development for the chromatographic analysis of basic compounds
      is to choose a system in which the band spacing can be varied dramatically,
      quickly, and conveniently while minimizing the tailing due to silanolphilic
      interactions. The thermally tuned tandem column (T3C) approach has been shown to
      provide an effective way to adjust stationary-phase selectivity for nonionic
      compounds. In this study, a tandem combination of an octadecylsilane (ODS) and a
      polybutadiene-coated zirconia (PBD-ZrO2) phase was used to separate nine
      antihistamines. Selectivity is tuned by independently adjusting the isothermal
      temperatures of the two columns. We found dramatic differences in the retention
      factors, elution sequences, and band spacing for the above set of basic drugs on
      the two types of columns. The T3C model has been used successfully to locate the
      optimal temperatures based on only four exploratory runs. The nine antihistamines
      were baseline separated on the tandem column combination even though they could
      not be separated on the individual phases. The effect of the buffer concentration
      on retention of the basic antihistamines was also studied. We conclude that
      cation-exchange interactions predominate on the PBD-ZrO2 phase, while reversed
      phase interactions are more important on the ODS phase. Interestingly, an
      increase in column temperature causes a significant increase in the retention on
      the ODS column and a decrease of retention on the PBD-ZrO2 column. This can be
      explained by the change in the analyte's degree of ionization with temperature.
      The T3C combination of silica- and zirconia-based RPLC columns is demonstrated to
      be a powerful approach for the separation of this mixture of basic analytes.

PMID- 11575797
TI  - Optimized gating scheme for rapid lifetime determinations of single-exponential
      luminescence lifetimes.
AB  - The rapid lifetime method (RLD) for determining excited-state lifetimes uses the
      ratio of the areas under two regions of the decay. To get good precision with the
      standard method, prior knowledge of the lifetime is essential to selecting the
      integration regions. As will be shown, the usual method of selecting integration
      regions is far from optimal. An optimal gating scheme that is more precise and
      much more forgiving in the selection of integration region than any of the prior
      methods will be shown. Monte Carlo simulations were performed to determine the
      optimal gating. Experimental data was used to confirm the capabilities of the
      optimized RLD. The speed of the optimal RLD is similar to the standard RLD but
      without the necessity of matching the integration interval to the lifetime for
      precise results.

PMID- 11575798
TI  - An integrated fluorescence detection system in poly(dimethylsiloxane) for
      microfluidic applications.
AB  - This paper describes a prototype of an integrated fluorescence detection system
      that uses a microavalanche photodiode (microAPD) as the photodetector for
      microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS). The prototype
      device consisted of a reusable detection system and a disposable microfluidic
      system that was fabricated using rapid prototyping. The first step of the
      procedure was the fabrication of microfluidic channels in PDMS and the
      encapsulation of a multimode optical fiber (100-microm core diameter) in the
      PDMS; the tip of the fiber was placed next to the side wall of one of the
      channels. The optical fiber was used to couple light into the microchannel for
      the excitation of fluorescent analytes. The photodetector, a prototype solid
      state microAPD array, was embedded in a thick slab (1 cm) of PDMS. A thin (80
      microm) colored polycarbonate filter was placed on the top of the embedded
      microAPD to absorb scattered excitation light before it reached the detector. The
      microAPD was placed below the microchannel and orthogonal to the axis of the
      optical fiber. The close proximity (approximately 200 microm) of the microAPD to
      the microchannel made it unnecessary to incorporate transfer optics; the pixel
      size of the microAPD (30 microm) matched the dimensions of the channels (50
      microm). A blue light-emitting diode was used for fluorescence excitation. The
      microAPD was operated in Geiger mode to detect the fluorescence. The detection
      limit of the prototype (approximately 25 nM) was determined by finding the
      minimum detectable concentration of a solution of fluorescein. The device was
      used to detect the separation of a mixture of proteins and small molecules by
      capillary electrophoresis; the separation illustrated the suitability of this
      integrated fluorescence detection system for bioanalytical applications.

PMID- 11575799
TI  - Coulomb fission event resolved progeny droplet production from isolated
      evaporating methanol droplets.
AB  - An electrodynamic balance was used to levitate a single methanol droplet while it
      evaporated down to, and just beyond, its first encountered Coulomb fission limit
      as ascertained by the time dependence of its laser light scatter signal. At its
      Coulomb limit, the primary droplet fragmented and approximately 81% of its net
      charge was released in the form of small droplets that are termed progeny. The
      window of time over which the progeny droplets were ejected from the
      electrodynamic balance was deltat = 850 ms, indicating that these droplets were
      formed with a range of mass-to-charge values. An average of 13.2 (+/-4.4) progeny
      droplets were detected as a result of this fragmentation event. On the assumption
      that the average initial radius of the progeny droplets were one-tenth the radius
      of the droplet undergoing the Coulomb fission event, approximately 50% of the
      total net charge ejected would not have been carried by the 13 progeny droplets
      detected.

PMID- 11575800
TI  - Identification of nucleotides with identical fluorescent labels based on
      fluorescence polarization in surfactant solutions.
AB  - A solution-phase steady-state polarization-based method for discriminating among
      the four DNA nucleotides labeled identically with tetramethylrhodamine is
      described and demonstrated. Labeled nucleotides were dissolved in buffered
      surfactant solutions. In room temperature 4.5 mM Triton X-100 solutions at
      neutral pH, the measured steady-state polarizations of tetramethylrhodamine
      labeled dATP, dCTP, dGTP and dUTP were 0.261 +/- 0.003, 0.112 +/- 0.003, 0.288 +/
      0.003, and 0.147 +/- 0.003, respectively. A blind test of 40 samples showed no
      errors in classification based on polarization. The reproducibility obtained
      during this study demonstrates that the four dye-labeled nucleotides can be
      discriminated with more than 99.8% confidence.

PMID- 11575801
TI  - Genotyping of simple and compound short tandem repeat loci using electrospray
      ionization Fourier transform ion cyclotron resonance mass spectrometry.
AB  - The utility of electrospray ionization Fourier transform ion cyclotron resonance
      (ESI-FIICR) mass spectrometry as a new approach for genotyping short tandem
      repeats (STRs) is demonstrated. STRs are currently valued as a powerful source of
      genetic information with repeats that range in structure from simple to
      hypervariable. Two tetranucleotide STR loci were chosen to evaluate ESI-FTICR
      mass spectrometry as a tool for genotyping: HUM-TH01, a simple STR with
      nonconsensus alleles, and vWA, a compound STR with nonconsensus alleles. For HUM
      TH01, the genotype (i.e., repeat number of each allele) was determined for each
      of 30 individuals using mass measurements of double-stranded amplicons. Low
      intensity peaks observed in the spectra of amplicons derived from heterozygous
      individuals were identified by mass as heteroduplexes that had formed between
      nonhomologous strands. Mass measurement of the double-stranded vWA amplicon was
      not sufficient for determining whether the individual was homozygous for allele
      subtype 18 or 18' since the amplicons differ by only 0.99 Da. Therefore, single
      stranded amplicons were generated by incorporating a phosphorylated primer,
      prepared using T4 polynucleotide kinase, into the PCR phase and subsequently
      digesting the bottom strand using lambda-exonuclease. Accurate mass measurements
      were obtained for the single-stranded amplicons using internal calibration and
      the addition of a correction factor to adjust for the natural variation of
      isotopic abundances, confirming that the individual is homozygous for allele 18.
      Our results clearly demonstrate that ESI-FTICR mass spectrometry is a powerful
      approach to characterize both simple and compound STRs beyond the capabilities of
      electrophoretic technologies.

PMID- 11575802
TI  - Organic chloramine analysis and free chlorine quantification by electrospray and
      atmospheric pressure chemical ionization tandem mass spectrometry.
AB  - Atmospheric pressure chemical ionization (APCI) and electrospray ionization
      (ESI), together with tandem mass spectrometry (MSn), are used to study the
      mechanism of chlorination of amines and to develop a method for qualitative and
      quantitative determination of organic chloramines. Cyclohexylamine and 1,4
      butanediamine (putrescine) are used as model compounds to investigate the
      mechanisms of the reactions between primary aliphatic amines and hypochlorous
      acid (aqueous Cl2). The chlorination products are identified and characterized by
      collision-induced dissociation (CID) and H/D exchange. Chlorination occurs by
      electrophilic addition of Cl+ and may be followed by HCl elimination, hydrolysis,
      or, in the case of diamines, amine elimination by intramolecular nucleophilic
      substitution. The relative rates of chlorination at amine and chloramine
      nitrogens are a function of pH and depend on the basicity of the amine. A novel
      method for active chlorine quantification using ESI or APCI mass spectrometry is
      suggested on the basis of the extent of chlorination of a sacrifical amine
      standard. This measurement has a limit of detection for N-chlorocyclohexylamine
      in the range of 0.1-10 microM, a linear dynamic range of 10(2)-10(3), and an
      accuracy of +/-10%, as determined for wastewater samples.

PMID- 11575803
TI  - Electron capture dissociation and infrared multiphoton dissociation MS/MS of an N
      glycosylated tryptic peptic to yield complementary sequence information.
AB  - Glycoproteins are a functionally important class of biomolecules for which
      structural elucidation presents a challenge. Fragmentation of N-glycosylated
      peptides, employing collisionally activated dissociation, typically yields
      product ions that result from dissociation at glycosidic bonds, with little
      occurrence of dissociation at peptide backbone sites. We have applied two
      dissociation techniques, electron capture dissociation (ECD) and infrared
      multiphoton dissociation (IRMPD), in a 7-T Fourier transform ion cyclotron
      resonance mass spectrometer, in the investigation of an N-glycosylated peptide
      from an unfractionated tryptic digest of the lectin of the coral tree, Erythrina
      corallodendron. ECD provided c and z. ions derived from the peptide backbone,
      with no observed loss of sugars. Cleavage at 11 of 15 backbone amine bonds was
      observed. The lack of cleavage at sites located close to the glycosylated
      asparagine residue may result from steric blocking by the glycan. IRMPD provided
      abundant fragment ions, primarily through dissociation at glycosidic linkages.
      The monosaccharide composition and the presence of three glycan branch sites
      could be determined from the IRMPD fragments. The two types of spectra, obtained
      with the same instrument, thus provide complementary structural information about
      the glycopeptide. The current result extends the applicability of ECD for
      glycopeptide analysis to N-glycosylated peptides and to peptides containing
      branched, highly substituted glycans.

PMID- 11575804
TI  - Accurate molecular mass determination of mycolic acids by MALDI-TOF mass
      spectrometry.
AB  - Mycolic acids, major and specific long-chain fatty (C70-C90) acid components of
      the mycobacterial cell envelope, were analyzed for the first time using matrix
      assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry
      operating in a reflectron mode. The various types of purified mycolates from
      representative mycobacterial species were analyzed using 2,5-DHB as matrix,
      because less than 10 pmol of mycolates was sufficient to obtain well-resolved
      mass spectra composed exclusively of pseudomolecular [M + Na]+ ions consistent
      with the structures deduced from the chemical analytical techniques applied to
      these molecules. Examination of the MALDI mass spectra demonstrated that the
      chain lengths of the various mycolates correlated with the growth rate of
      mycobacterial strains. Although slow growers, such as Mycobacterium tuberculosis
      and Mycobacterium ulcerans, produced a series of odd carbon numbers (C74-C82) of
      alpha-mycolic acids, rapid growers synthesized both odd and even carbon numbers.
      In addition, the main chain of oxygenated mycolic acids from slow growers were
      four to six carbon atoms longer than the corresponding alpha-mycolic acids,
      whereas rapid growers elaborated oxygenated homologues possessing the same chain
      lengths as their alpha-mycolic acids. Furthermore, a comparative analysis of the
      crude fatty acid mixtures from a wild-type strain of M. tuberculosis and its
      isogenic mutant effected in the synthesis of oxygenated mycolates by MALDI mass
      spectrometry revealed structural differences between the alpha-mycolates from the
      two strains. Thus, this technique appeared to be a rapid and highly sensitive
      technique for the analysis of mycolic acids, not only by providing accurate
      molecular masses and new structural information, but also by both reducing sample
      consumption and saving time.

PMID- 11575805
TI  - A miniaturized liquid core waveguide-capillary electrophoresis system with flow
      injection sample introduction and fluorometric detection using light-emitting
      diodes.
AB  - A novel miniaturized capillary electrophoresis (CE) system is described where a
      Teflon AF-coated silica capillary serves both as the separation channel and as a
      transversely illuminated liquid core waveguide. This device uniquely uses flow
      injection (FI)-based split-flow sample introduction through a falling-drop
      interface. An H-channel structure fixed on a microscope glass slide utilizes a
      horizontal separation capillary with tubular sidearms on each end that serve as
      inlet and outlet flow-through electrode reservoirs. The inlet reservoir also
      functions as a falling-drop interface for coupling to the FI system. A blue LED
      is used as excitation source. A large-core optical fiber takes the emitted
      fluorescence to an inexpensive PMT with two layers of green plastic used for
      optical filtering. No focusing arrangement is needed. Continuous FI introduction
      of a series of 30-microL samples containing a mixture of of fluorescein
      isothiocyanate (FITC)-labeled amino acids allowed a throughput rate up to 144
      samples/ h, with approximately 2% carryover and good precision (3.2% RSD).
      Baseline separation was achieved for FITC-labeled arginine, phenylalanine,
      glycine, and FITC in sodium tetraborate buffer (pH 9.5) with plate heights of 5.4
      5.5 microm and plate numbers of 2.34 x 10(4)-2.37 x 10(4) under electrical field
      strengths of 214 V/cm for injection and 500 V/cm for separation (14-cm capillary,
      48-microm i.d.). Detection limits (S/N = 3) were 1.3 microM for arginine and 1.9
      microM for phenylalanine and glycine.

PMID- 11575806
TI  - Is ASAIO an existentialist society?

PMID- 11575807
TI  - Thrombogenic influence of biomaterials in patients with the Omni series heart
      valve: pyrolytic carbon versus titanium.
AB  - An opportunity to assess the thromboembolic rates caused by the construction
      materials on valve replacements is possible with the Omni series of mechanical
      heart valves. The Omnicarbon and Omniscience valves are identical in form but
      differ in that the Omnicarbon valve is constructed entirely of pyrolytic carbon,
      whereas the Omniscience valve uses titanium for its housing, the rest of its
      structure being pyrolytic carbon. The literature was reviewed and a comparison in
      similar groups of patients was made between these two model valves for their
      thromboembolic rates in the mitral and aortic positions. A total of 569 aortic
      Omnicarbon valves (4,146 patient years [pt yrs.1) had a thromboembolic events
      (T/E rate) of 0.5% compared with 1.7% for 468 aortic Omniscience (1,552 pt yrs);
      p < 0.0001. A total of 298 mitral Omnicarbon valves (3,333 pt yrs) had a T/E rate
      of 1.6% compared with 2.6% for 716 mitral Omniscience valves (2,134 pt yrs), p <
      0.001. There was no difference in the anticoagulation management between the two
      model valves although the Omniscience valve required higher prothrombin or
      International Normalized Rate maintenance levels, which resulted in higher
      bleeding rates among patients with Omniscience valves.

PMID- 11575809
TI  - Rationale for daily hemodialysis.

PMID- 11575808
TI  - Acute in vivo testing of an intravascular respiratory support catheter.
AB  - Current treatment for acute respiratory failure (ARF) includes the use of
      mechanical ventilation and/or extracorporeal membrane oxygenation, both of which
      can exacerbate lung injury. Intravenous respiratory support, using hollow fiber
      membranes placed in the vena cava, represents an attractive potential treatment
      for ARF, which could help reduce or eliminate ventilator induced trauma and/or
      other problems. Our group has been developing a respiratory support catheter (the
      Hattler catheter [HC]) that consists of a constrained hollow fiber bundle with a
      centrally located balloon. The balloon can be pulsated rapidly to increase blood
      flow across the fibers and decrease diffusional transfer resistance there, thus
      increasing gas exchange. The purpose of this study was to evaluate the HC in
      acute animal implants and to compare performance with that achieved in previous
      ex vivo studies. The HC was implanted into four calves by means of the external
      jugular vein and placed in the superior and inferior vena cava spanning the right
      atrium. Gas exchange, hemodynamics, and hematologic parameters were assessed over
      a range of balloon pulsation rates from 30 to 300 beats/minute. A <10% reduction
      in cardiac output was associated with catheter insertion and operation. The
      maximum CO2 exchange rate occurred at the highest pulsation rate and averaged 56
      +/- 3 ml/min, or 327 +/- 15 ml/min per m2 when averaged to catheter membrane
      area, a level comparable to that achieved in the previous ex vivo studies.
      Balloon pulsation did not produce significant levels of hemolysis, as plasma-free
      hemoglobin remained below 10-15 mg/dl.

PMID- 11575810
TI  - The case for short daily hemodialysis, why sDHD will be the predominant modality
      for frequent dialysis.

PMID- 11575811
TI  - The case for nocturnal hemodialysis.

PMID- 11575812
TI  - Short daily versus long nocturnal hemodialysis. Daily/Nocturnal Dialysis Study
      Group.

PMID- 11575813
TI  - Nocturnal dialysis in the inner city.

PMID- 11575814
TI  - Cost of daily hemodialysis.

PMID- 11575815
TI  - The role of managed care in daily dialysis.

PMID- 11575816
TI  - Will HCFA/CMS' new process and proposed criteria for making national coverage
      decisions help or hurt payment for DHD?

PMID- 11575817
TI  - Is HCFA's reimbursement policy controlling quality of care for end-stage renal
      disease patients?

PMID- 11575818
TI  - My experience with daily dialysis.

PMID- 11575819
TI  - Thoughts on the ASAIO conference and text of the presentation.

PMID- 11575820
TI  - Safety observations in phase I clinical evaluation of the Excorp Medical
      Bioartificial Liver Support System after the first four patients.
AB  - A Phase I clinical safety evaluation of the Excorp Medical, Inc, Bioartificial
      Liver Support System (BLSS) is in progress. Inclusion criteria are patients with
      acute liver failure of any etiology, presenting with encephalopathy deteriorating
      beyond Parson's Grade 2. The BLSS consists of a blood pump, heat exchanger to
      control blood temperature, oxygenator to control oxygenation and pH, bioreactor,
      and associated pressure and flow alarm systems. Patient liver support is provided
      by 70-100 g of porcine liver cells housed in the hollow fiber bioreactor. A
      single support period evaluation consists of 12 hour extracorporeal perfusion
      with the BLSS sandwiched between 12 hours of pre (baseline) and 12 hours of post
      support monitoring. Blood chemistries and hematologies are obtained every 6 hours
      during monitoring periods and every 4 hours during perfusion. Physiologic
      parameters are monitored continuously. The patient may receive a second treatment
      at the discretion of the clinical physician. Preliminary evaluation of safety
      considerations after enrollment of the first four patients (F, 41, acetaminophen
      induced, two support periods; M, 50, Wilson's disease, one support period; F, 53,
      acute alcoholic hepatitis, two support periods; F, 24, chemotherapy induced, one
      support period) is presented. All patients tolerated the extracorporeal perfusion
      well. All patients presented with hypoglycemia at the start of perfusion,
      treatable by IV dextrose. Transient hypotension at the start of perfusion
      responded to an IV fluid bolus. Only the second patient required heparin
      anticoagulation. No serious or unexpected adverse events were noted. Moderate
      biochemical response to support was noted in all patients. Completion of the
      Phase I safety evaluation is required to fully characterize the safety of the
      BLSS.

PMID- 11575821
TI  - Construction of a differentiated human hepatocyte cell line expressing the herpes
      simplex virus-thymidine kinase gene.
AB  - Transient support using a hybrid artificial liver (HAL) device is a promising
      treatment for the patients with acute liver failure. Primary human hepatocytes
      are an ideal source for HAL therapy; however, the number of human livers
      available for hepatocyte isolation is limited by competition for use in whole
      organ transplantation. To overcome this problem, we previously established a
      highly differentiated human fetal hepatocyte cell line OUMS-29. Considering the
      potential risk when using these genetically engineered cells in humans,
      additional safeguards should be added to make the cells more clinically useful.
      In this work, the herpes simplex virus thymidine kinase (HSVtk) gene was
      retrovirally introduced into OUMS-29 cells. One of the HSVtk-expressed clones,
      OUMS-29/thymidine kinase (TK), grew in chemically defined serum free medium and
      expressed the genes of albumin, asialoglycoprotein receptor, glutamine
      synthetase, glutathione-S-transferase pi, and blood coagulation factor X. In
      vitro sensitivity of the cells to ganciclovir was evaluated. Intrasplenic
      transplantation of 50 x 10(6) OUMS-29/TK cells prolonged the survival of 90%
      hepatectomized rats compared with medium injection alone (control). In the
      present study, we have established highly differentiated immortalized human
      hepatocytes with tight regulation. The cells may be clinically useful for HAL
      treatment.

PMID- 11575822
TI  - Expansion of human hepatocyte populations by a retroviral gene transfer of simian
      virus 40 large T antigen.
AB  - A hybrid artificial liver (HAL) could be used to treat acute liver failure or to
      serve as a temporary support until orthotopic liver transplantation is available.
      Primary human hepatocytes are ideal as a source of hepatic function in a HAL
      device. However, the worldwide shortage of human livers available for hepatocyte
      isolation severely limits this form of therapy. A possible alternative is to use
      a tightly regulated cell line that can be economically grown in culture to have
      differentiated liver function. In this work, human hepatocytes were immortalized
      with a retroviral vector SSR#69 expressing the genes of simian virus 40 large T
      antigen and herpes simplex virus-thymidine kinase. One of the resulting clones,
      NKNT-3 , showed the gene expression of differentiated liver function and were
      sensitive to the antiviral agent ganciclovir. When transplanted into the spleen
      of rats subjected to 90% hepatectomy, NKNT-3 cells prolonged the survival of 90%
      hepatectomized rats. The cells provide the advantages of unlimited availability,
      sterility, uniformity, and freedom from pathogens. This work represents a
      potential novel strategy for resolving the organ shortage that currently limits
      the use of primary human hepatocytes to develop a HAL.

PMID- 11575823
TI  - Development of an ambulatory artificial lung in an ovine survival model.
AB  - We are developing an artificial lung (AL) as an eventual bridge to lung
      transplant or recovery. The device is rigidly housed, noncompliant, and has a
      very low resistance to blood flow. In eight sheep, arterial cannulae were
      anastomosed end-to-side to the proximal and distal main pulmonary artery, and
      attached to the AL. A pulmonary artery snare between anastomoses diverted full
      pulmonary blood flow through the AL. Eight of eight sheep survived the
      preparation. Mean pressure gradient across the AL was 8 mm Hg (3 Wood units; 8 mm
      Hg/2.8 L/min). Four of eight sheep tolerated immediate full diversion of blood
      flow and died at 24 and 40 hours (exsanguination) or 168 and 168 hours (elective
      sacrifice). Four of eight sheep were intolerant of full flow: two died of right
      heart failure at <8 hours with full flow through the device (full snare); the
      other two survived with partial device flow (partial snare), but the device
      clotted. These two then underwent successful closed-chest cannula thrombectomy
      and device change-out at 53 and 75 hours, and subsequently tolerated full flow.
      Long-term (up to 7 day) survival with complete diversion of pulmonary blood flow
      through a non-compliant, low-resistance AL is possible. Initial right heart
      failure in this model was 50% (4 of 8).

PMID- 11575824
TI  - Blood trauma induced by clinically accepted oxygenators.
AB  - Hemolysis remains one of the most serious problems during cardiopulmonary bypass
      (CPB), extracorporeal membrane oxygenation (ECMO), and percutaneous
      cardiopulmonary support (PCPS). However, the hemolytic characteristics associated
      with oxygenators are not well defined. A specialized hemolysis test protocol for
      oxygenators was developed. A comparative study was performed following this
      protocol to determine the hemolytic characteristics of the clinically available
      oxygenators during CPB; pressure drop measurements in the blood chamber were also
      performed. Four oxygenators (Medtronic Affinity, Cobe Optima, Terumo Capiox SX25,
      and Bard Quantum) were evaluated. Fresh blood from healthy Dexter calves
      anticoagulated with citrate phosphate dextrose adenine solution was used. The
      blood flow was fixed at 5 L/min, similar to that used in CPB. The Normalized
      Index of Hemolysis for Oxygenators (NIHO) has been modified according to the
      American Society of Testing and Materials (ASTM) standards. The NIH value, which
      was obtained from the circuit without an oxygenator, was subtracted from the
      primary NIH value, obtained from the circuit with an oxygenator to eliminate the
      effects of a centrifugal pump or other artifacts. The NIHO value was the lowest
      in the Affinity (0.0116 +/- 0.0017) and increased from Affinity < Optima (0.0270
      +/- 0.0038) < Capiox (0.0335 +/- 0.0028) < Quantum (0.0416 +/- 0.0015 g/100 L).
      The Optima and Capiox did not demonstrate a significant difference. In addition,
      this NIHO value has a close relationship to the pressure drop. In conclusion,
      this new evaluation method is suitable to compare the biocompatibility
      performance of different types of clinically available oxygenators for CPB usage.

PMID- 11575825
TI  - Replacement of a tracheal defect with autogenous mucosa lined tracheal prosthesis
      made from polypropylene mesh.
AB  - Reliable prosthetic or tissue grafts for the trachea have not, as yet, been
      developed for reconstruction of large, circumferential tracheal defects. Major
      limitations are anastomotic dehiscence and stenosis, attributed to the poor
      epithelialization and vascularization of the prosthetic graft. We have developed
      a new tracheal prosthesis that has a well vascularized and viable mucosa. The
      prosthesis consists of a Prolene mesh reinforced with polypropylene rings, and
      coated with gelatin. We lined the luminal surface of the prosthesis with
      transplanted autogenous oral mucosa, wrapped the prosthesis with greater omentum,
      and placed it in the peritoneal cavity for 2 weeks. Complete surgical resection
      and replacement of a segment (5 cm in length, 8 to 10 tracheal rings) of the
      thoracic trachea was then performed in nine adult mongrel dogs. The transplanted
      mucosa was well vascularized and maintained its normal histology in
      prereplacement analysis. Dogs with tracheal replacement regained their full
      activity and did not show any respiratory problems until sacrifice at 1, 2, and 6
      months. After 6 months, the prostheses were completely incorporated by the host
      trachea in all dogs and confluent epithelialization was confirmed histologically
      from the upper to the lower anastomotic site of the prosthesis; furthermore, the
      transplanted mucosal cells had changed to ciliated columnar epithelium.

PMID- 11575826
TI  - Effects of systemic hemodynamics on flow within vascular accesses used for
      hemodialysis.
AB  - Absolute value of access flow (QA) and change in flow (deltaQA) over time are
      major determinants of access patency. However, QA may change in response to
      variation in systemic hemodynamics among dialysis sessions. We examined the
      effect of mean arterial pressure (MAP), cardiac output (CO), and segmental
      resistances (R) on QA. Access flow and CO (L/min) were determined by Transonic
      ultrasound dilution. Static intra-access pressures (mm Hg) at the arterial
      segment (AS) and venous segment (VS) were determined with the access unoccluded.
      During access occlusion (O), the AS pressure was equated to arterial pressure
      (MAPo), whereas the VS pressure reflected venous pressure (VP). Total and
      segmental vascular resistances (mm Hg-min/L) were calculated as deltaP/Q. We
      studied 58 arteriovenous (AV) grafts and 35 autologous AV fistulae (AVF) with
      measurements on two or more occasions in 43 grafts and 25 AVF. MAPC differed from
      MAPo by >20 mm Hg in 22% of patients. AS (58 +/- 2 vs. 31 +/- 2) and VS (40 +/- 1
      vs. 25 +/- 2) were greater in grafts than in AVF, whereas VP was equal. Access
      flow (0.91 +/- 0.03 vs. 0.91 +/- 0.05 L/min), cardiac output (5.1 +/- 0.1 vs. 5.5
      +/- 0.2 L/min), and total access resistance (115 +/- 5 vs. 11 +/- 6) were equal
      in grafts and AVF, but non-access systemic R was lower in patients with AVF that
      those with grafts (26 +/- 1 vs. 30 +/- 1). AS and VS resistances were greater in
      AVF than grafts (87 +/- 6 vs. 54 +/- 3 and 37 +/- 3 vs. 16 +/- 3). Multivariate
      analysis indicated that CO and ipsilateral MAPo affected flow in both access
      types. In grafts, all three access resistance elements, AS, VS, and total
      independently influenced flow, whereas in AVF, the VS did not. Unexpectedly, the
      ratio of systemic to access resistance also influenced access flow. The pressure
      in the venous system draining the access affected access flow in AVF but not
      grafts. We conclude that the hemodynamics of grafts and AVF differ. Cardiac
      output, MAP, and the arterial segment resistance influence QA in both access
      types and need to be considered when evaluating QA as part of the trend analysis
      for detecting access dysfunction.

PMID- 11575827
TI  - Antibodies to prothrombin, factor V, and beta2-glycoprotein I and vascular access
      thrombosis.
AB  - We studied 88 hemodialysis patients for the presence of antibodies to human
      factor II (hFII), bovine factor V (bFV), and human beta2-glycoprotein 1
      (beta2GPI). Forty-one patients had elevated anti-hFII antibodies, 17 had elevated
      anti-bFV antibodies, and 9 had elevated anti-beta2GPI antibodies. Fifty-two
      patients had elevated antibodies to one or more protein. Patients with PTFE
      grafts had elevated antibodies most frequently (21 [75%] vs. 20 fistulas [45%; p
      = 0.016 compared with PTFE] and 11 tunneled catheters [68.8%]). Twelve of 13
      patients (92.3%) with PTFE grafts and thrombosis had elevated antibody levels,
      compared with 9 of 15 without thrombosis (60%; p = 0.049). The number of
      thromboses and mean thrombosis rates were significantly higher in PTFE patients
      with antibodies (1.24 vs. 0.14 thromboses, p < 0.01; 42.67 vs. 6.44
      thromboses/100 patient years, p < 0.05). When analyzed individually, thrombotic
      complications occurred more frequently in patients with PTFE grafts and elevated
      anti-bFV antibodies (p = 0.016), but did not correlate with anti-hFII or anti
      beta2GPI antibodies. Thrombotic complications did not correlate with elevated
      antibody levels in patients with AV fistulas or cuffed catheters. In conclusion,
      hemodialysis patients with PTFE grafts frequently have elevated antibodies to
      FII, FV, and beta2GPI, and the presence of elevated antibody levels to one or
      more of these proteins is associated with an increased thrombotic risk. Further
      studies are necessary to determine whether limiting exposure to bovine thrombin
      preparations will decrease the incidence of these antibodies and PTFE graft
      thrombosis.

PMID- 11575828
TI  - Anemia and iron target realization in 1998: clinical management of anemia in
      1,639 patients on hemodialysis.
AB  - Anemia management in hemodialysis patients continues to evolve, and recently,
      greater emphasis has been placed on the wider use of intravenous iron to maintain
      adequate iron levels. This survey provides scarcely available yet potentially
      useful information on the clinical treatment of anemia in a large cohort of
      hemodialysis patients. The erythropoietin and iron administration details and
      pertinent laboratory measurements from 1,639 patients were analyzed for the month
      of December, 1998. A standardized protocol had been used in that erythropoietin
      was begun at a total weekly dose of 150 U/kg IV or 100 U/kg subcutaneously and
      was then adjusted to maintain a hematocrit (Hct) of 33-36%. Iron supplements,
      oral, IV, or both, were administered to maintain percent transferrin saturation
      (TSAT) at 20-30% and/or a serum ferritin of 100-500 ng/ml. No intravenous iron
      was administered if the ferritin was more than 500 ng/ml. Although 82% of
      patients were on iron supplementation and, among them, 58% were on IV iron, the
      percentage of patients with TSAT >20, i.e., bioavailable iron, was only 51%. The
      serum ferritin was high at 498 +/- 10 ng/ml (mean +/- SEM) and 88% and 10% of
      patients had serum ferritin >100 and >1,000 ng/ml, respectively, suggestive of
      sequestration of part of the infused iron. Erythropoietin was administered to 96%
      of patients, 99.5% by IV route. The latter was consistent with the US dialysis
      population at large but in variance with DOQI preference for the subcutaneous
      route. The target Hct range of 33-36 was found in 33%, with a mean Hct of 34.0 +/
      0.12. When the data were reanalyzed by excluding patients who had not been
      receiving erythropoietin and had not been on dialysis for at least 3 months, the
      percentage of patients achieving the target Hct increased to 37%. Paired analysis
      of 875 patients present in 1996 and 1998 showed that, although there was a marked
      increase in the use of IV iron, the improvement in anemia was modest, and there
      was evidence for increased iron accumulation. In summary, this 1998 survey on the
      clinical practice of anemia management in a large hemodialysis population
      indicates that there is a marked increase in need-based IV iron usage that was
      associated with modest improvement in anemia and evidence for increased iron
      storage. A maintenance iron dosing protocol with smaller doses of iron, such as
      25 mg of iron dextran per hemodialysis, may make bioavailable iron continuously
      present for erythropoiesis, yet may reduce the chance for iron catalyzed lipid
      peroxidation and tissue iron deposition.

PMID- 11575829
TI  - Do different dialytic techniques have different atherosclerotic and antioxidant
      activities?
AB  - To compare the chronic effect of several dialytic techniques (bicarbonate
      dialysis, BHD; acetate free biofiltration, AFB; hemodiafiltration, HDF; paired
      filtration dialysis, PFD) on atherosclerosis and antioxidant activity, three
      different indices were created. The first (atherosclerotic index = AI) is formed
      using the sum of three plasma substances: MDA, Hcy, and Cys (malondialdehyde,
      homocysteine, cysteine). The second (antioxidant activity index = AOAI) is the
      sum of five erythrocyte (E) parameters: E-GSH, GPx, CAT, SOD, GR (E-glutathione,
      E-glutathione peroxidase, E-catalase, E-superoxide dismutase, E-glutathione
      reductase). The third (defense index = DI) is derived from the previous two:
      (AOAI - AI). The indices were so expressed as AI in mmol/L, AOAI in U/g
      hemoglobin (Hb), and DI in arbitrary units. These indices were calculated in 20
      controls and 51 chronic HD patients (26 female, 25 male) before, during, and
      after the first session of the week. HD patients were divided according to their
      dialytic technique: BHD, n = 35; AFB, n = 5 patients; HDF, n = 7 patients; or PFD
      = 4 patients. All patients had been treated with a given technique for at least
      12 months, before entering the study. As expected, HD patients had AI values
      higher than controls, both before and after the session, with a mean value of 541
      (before) and 331 (after), whereas controls had a mean value of 205. The AOAI was
      lower than controls, both before and after the session, the mean value being
      1,122 (before) and 1,582 (after), that of controls being 2,424. In all cases, PFD
      gave the best "acute" results; at the end of a PFD session, near normal values of
      AI, AOAI, and DI (defensive index = AOAI - AI) were obtained.

PMID- 11575830
TI  - Prediction of the shelf life of cellulose acetate hemodialyzers by Monte Carlo
      simulation.
AB  - A previous investigation by our laboratory linked cellulose acetate degradation
      with adverse health effects in hemodialysis patients. To establish the
      accumulation of degradation products with time, a Monte Carlo model of
      degradation kinetics was developed. The model tracks changes in a population of
      molecules representative of the dialyzer membrane during the degradation process.
      The degradation calculation is a two step process: First, the model uses a random
      number to select an individual polymer molecule out of the population, and then a
      second random number is used to identify a site on the selected molecule for the
      degradation reaction to occur. After the reaction calculation, the resulting
      degraded molecules are redistributed into the population. The course of the
      reaction is determined by recalculating the molecular weight averages in the
      changing population as the calculations proceed. The model was validated using
      gel permeation chromatography molecular weight results and total acetyl content
      measurements on dialyzers stored up to 13.3 years after manufacture. It was found
      that the degradation reactions can be accurately modeled as random events and
      that the chain scissions and deacetylation events occur at constant rates. The
      shelf life of these devices was estimated using the model predictions and animal
      test results.

PMID- 11575831
TI  - Utility of the inferior vena cava diameter as a marker of dry weight in
      nonoliguric hemodialyzed patients.
AB  - We have previously reported that the maximal inferior vena cava (IVC) diameter
      during quiet expiration (IVCe) measured by ultrasonography correlates well with
      the amount of body fluid, especially the circulating blood volume(2) and proposed
      using the criteria of IVC diameter to determine dry weight (DW) in anuric
      hemodialyzed (HD) patients: standard IVCe of pre- and post-HD are 14.9 +/- 0.4
      and 8.2 +/- 0.3 mm, respectively (1). However, the same post-HD IVC criterion
      should not be applied to nonoliguric HD patients because it could result in rapid
      deterioration of residual renal function due to forced dehydration. Although the
      biochemical DW marker plasma atrial natriuretic peptide (ANP) is useful to
      evaluate hypervolemia but not hypovolemia, both hyper- and hypovolemia can be
      detected by IVC measurement. In the present study, we investigated whether the
      IVC diameter serves as an optimal evaluation of DW in nonoliguric HD (NO-HD)
      patients, avoiding not only overhydration but also dehydration. The IVCe and
      plasma ANP levels were measured in 14 euvolemic patients with chronic renal
      failure at conservative period (CP-CRF) and 11 NO-HD patients, in whom the
      average daily urine volume was more than 500 ml/day. In NO-HD patients, DW was
      adjusted to attain the euvolemic state with normotensive blood pressure, lack of
      edema, and lack of temporal oliguria after HD. The ANP in CP-CRF patients was
      109.3 +/- 15.3 pg/ml, and pre- and post-HD ANP levels in NO-HD patients were
      145.3 +/- 23.5 and 97.5 +/- 13.5 pg/ml, respectively. IVCe in CP-CRF was 13.4 +/-
      0.9 mm, and pre- and post-HD IVCe in NO-HD patients were 14.2 +/- 1.0 mm and 11.9
      +/- 0.9 mm, respectively. Although the post-HD IVCe was greater (i.e., less
      hypovolemic) than that in anuric HD patients, and close to the IVCe in CP-CRF,
      pre-HD IVCe was comparable with that in anuric HD patients. In addition, the pre
      HD ANP level was no higher than that in CP-CRF. Thus, in NO-HD patients, the post
      IVCe of 11.9 +/- 0.9 mm would be a marker for an appropriate DW setting avoiding
      severe post-HD dehydration as well as excessive hypervolemia during the
      interdialytic period.

PMID- 11575832
TI  - Direct detection of red blood cell fragments: a new flow cytometric method to
      evaluate hemolysis in blood pumps.
AB  - Pump induced hemolysis is presently evaluated by measuring plasma free hemoglobin
      (fHb). However, this method has disadvantages because quantification of fHb
      depends on hematocrit (HCT) and hemoglobin (Hb) levels. The aim of this work was
      to devise a hemoglobin independent method, capable of quantifying cell trauma
      directly by measuring the number of red blood cell (RBC) fragments. Whole blood
      flow cytometry was used to quantify circulating RBC fragments derived from a
      roller pump (Sarns, Inc. Model 2 M 6,002) and a centrifugal pump (Gyro C1E3,
      Kyocera Corp.). The pumps were tested in a mock circuit for 2 hr (5 L/min flow
      against 100 mm Hg pressure head). Red blood cell fragments were quantified by a
      phycoerythrin (PE) labeled glycophorin A antibody specific for erythrocytes. Red
      blood cell fragments were smaller than the intact RBC population and overlapped
      in size with the platelet population (based on forward- and side-light scattering
      measurements). For the roller pump, the values for RBC fragments increased from
      1,090 +/- 260/microl at 0 min to 14,880 +/- 5,900/microl after 120 min. In
      contrast, using the centrifugal pump, there was little increase in RBC fragments
      (from 730 +/- 270/microl at 0 min to 1,400 +/- 840/microl after 120 min). Flow
      cytometry can be used for the rapid, sensitive, hemoglobin independent evaluation
      of pump induced RBC trauma.

PMID- 11575834
TI  - Sustained skeletal muscle power for cardiac assist devices: implications of
      metabolic constraints.
AB  - A device to harness power from skeletal muscle contracting in a linear
      configuration is under development. This application requires a sustained level
      of power that is dependent upon muscle mechanics and metabolic properties. A
      biomechanical muscle model and a metabolic model constructed from experimental
      data were used to predict maximum power available in a sustainable region of
      loading and stimulation conditions. Latissimus dorsi (LD) of four goats were
      evaluated in vivo after a 10 week in situ conditioning protocol with an implanted
      Telectronics myostimulator. The LD insertion was reconnected to a hydraulic
      loading system, allowing isometric and isotonic contractions for biomechanical
      characterization. Metabolic utilization was measured by a thermister based
      myothermic technique. Brief fatigue tests of working isotonic contractions
      revealed stimulation conditions associated with sustained power. The results show
      metabolic utilization was dependent on contraction duration, rate, force, and
      stroke. The region of sustainable contractions was found for a range of durations
      of 0.1 to 0.6 sec and rates of 10 to 120 bpm. The boundary for the sustainable
      power region was well approximated by a constant value of metabolic utilization.
      A constant duty cycle (contraction to cycle duration ratio) also approximated the
      sustained power but differed by as much as 30% during the shorter contraction
      durations. The results demonstrate that a mechanical muscle model can predict
      maximum sustained power when the operating conditions are constrained to a
      sustainable range determined by a metabolic model. Furthermore, metabolic
      constraints influence the optimum conditions for sustained power needed in the
      design of skeletal muscle powered assist devices.

PMID- 11575833
TI  - Left ventricular assist system recipients exposed to bovine thrombin preparations
      have a higher frequency of antiphospholipid antibodies than nonexposed
      recipients.
AB  - After left ventricular assist system (LVAS) placement, recipients often develop
      antiphospholipid antibodies (aPL) that are associated with thrombosis. Fibrin
      glue containing a bovine thrombin preparation is used routinely in LVAS placement
      surgery. We investigated whether exposure to the thrombin preparation is
      responsible for stimulating aPL development in LVAS recipients. Pre-LVAS and
      weekly post-LVAS sera from six fibrin glue-exposed LVAS recipients and five
      nonexposed recipients were tested by enzyme-linked immunosorbent assay for IgG,
      IgA, and IgM anti-phosphatidylserine (aPS), anticardiolipin (aCL), anti
      phosphatidylethanolamine (aPE), and anti-phosphatidylcholine (aPC). Fibrin glue
      exposed recipients developed a significantly greater number of aPL than the
      nonexposed recipients (24 vs. 8; p = 0.0069). In particular, a higher frequency
      of IgG aCL (6/6 vs. 1/5; p = 0.015) and IgG aPE (4/6 vs. 0/5; p = 0.045) were
      noted. Exposure to the bovine thrombin component of fibrin glue seems to
      stimulate aPL development in LVAS recipients.

PMID- 11575835
TI  - Gastric intramucosal pH during lower body circulatory arrest under open distal
      anastomosis with selective cerebral perfusion in aortic arch repair.
AB  - Selective cerebral perfusion (SCP) and open distal anastomosis (OD) with
      hypothermia has been used as a popular means for circulatory assistance in aortic
      arch surgery. Although SCP has become accepted for brain protection, the
      influence of OD accompanying circulatory arrest on lower body ischemia is not
      known. We studied gastric tonometry (gastric intramucosal pH [pHi]) to estimate
      splanchnic ischemia during OD, and its relationship to postoperative organ
      function. In five patients (pts) (range, 65-78 years; mean, 71 years; group OD)
      who underwent arch replacement using SCP and OD with moderate hypothermia (25
      degrees C) during the period from March to August of 1999, pHi was measured
      precardiopulmonary bypass (pre-CPB), 30 min of CPB (CPB30), 10 min after OD
      (OD10), at end of CPB, and post-CPB. Eight pts (range, 52-78 years; mean; 66
      years) who underwent standard CPB (33 degrees C) during the same period (coronary
      artery bypass surgery in six and valve surgery in two) served as controls (group
      C). In group OD, pHi was significantly decreased at OD10 (7.35 +/- 0.03 at CPB30
      vs. 7.23 +/- 0.07 at OD10, p < 0.05) but recovered by the end of CPB (7.32 +/-
      0.02). Creatinine clearance on the first postoperative day (1POD) was
      significantly (p < 0.05) lower in group OD (82 +/- 40 ml/min) than in group C
      (126 +/- 25 ml/min), although there was no significant difference in preoperative
      values between the two groups. The pHi at OD10 did not correlate with the
      duration of OD (range, 30-47 min; mean, 38 min), whereas pHi at OD10
      significantly correlated with BUN (r = -0.973, p = 0.0054), Cr(r = -0.977, p =
      0.0043), and CCr (r = 0.908, p = 0.0328) on 1POD. One patient in group OD
      developed paraplegia and renal failure postoperatively. His pHi at OD10 was
      severely decreased to 7.11. These results suggest that intraoperative monitoring
      of pHi may be useful for the evaluation of visceral organ ischemia during OD in
      arch replacement and may contribute to improved technique for circulatory
      assistance in aortic surgery.

PMID- 11575836
TI  - Computational fluid dynamics and experimental validation of a microaxial blood
      pump.
AB  - Intravascular application of microaxial blood pumps as heart assist devices
      requires a maximum in size reduction of the pump components. These limitations
      affect the design process in many ways and restrict the number of applicable
      experimental procedures, but a detailed knowledge of the hemodynamics of the pump
      is of great interest for efficiency enhancement and reduction of blood trauma and
      thrombus formation. Computational fluid dynamics (CFD) offers a convenient
      approach to this goal. In this study, the inlet, vane, and outlet regions of a
      microaxial blood pump used as an intraaortic left ventricular assist device are
      analyzed by CFD and 3-dimensional (3-D) particle tracking velocimetry (PTV). For
      this purpose, a mock loop is set up that facilitates 3-D flow visualization. Flow
      in the main part of this testing device is modeled and computed by means of CFD.
      Pump head/flow (HQ) characteristics, axial pressure distribution, and particle
      images are then compared with numerical flow data. Results show that the pump
      performance characteristics, as well as inlet and outlet swirl predicted by the
      CFD model, are quite accurate compared with measured data. Proper boundary
      condition definitions and spatial discretization topology requirements for
      satisfactory results are discussed.

PMID- 11575837
TI  - Performance of a newly developed implantable centrifugal blood pump.
AB  - The performance of the newly developed implantable centrifugal blood pump was
      investigated in vitro. The pump was developed with the end goal of building a
      versatile system that includes a left ventricular assist system with an internal
      secondary battery or an implantable biventricular assist system with two
      implantable blood pumps. The hydrodynamic characteristics and efficiency of the
      blood pump were evaluated, and the mechanical damage to the blood caused by the
      blood pump was assessed through a hemolysis test using fresh goat blood. The pump
      could generate 120 mm Hg at a flow rate of 5 L/min and a motor speed of 2,500
      rpm. The electric input power to the pump was approximately 5 watts under these
      working conditions. The hemolysis caused by the pump was a bit higher than that
      by the former model, but stayed within an acceptable range. Performance of the
      pump in vitro was considered sufficient for a left ventricular assist device,
      although further design improvement is necessary in terms of hemolysis and system
      efficiency to improve biocompatibility of the pump.

PMID- 11575838
TI  - An unusual complication associated with the Carpentier-Edwards porcine
      bioprosthesis.
AB  - Primary tissue failure of bioprosthetic heart valves refers primarily to
      calcification of the leaflets of the bioprosthesis. A 75 year old patient
      underwent reoperation 15 years after mitral valve replacement with a Carpentier
      Edwards porcine bioprosthesis. The extracted bioprosthetic valve was found to
      have one prolapsed leaflet and a small amount of calcification on all three
      leaflets without tear or perforation. The two commissures suspending the
      prolapsed leaflet were detached, causing mitral valve regurgitation.

PMID- 11575839
TI  - The use of alteplase for the resolution of an intravesical clot in a neonate
      receiving extracorporeal membrane oxygenation.
AB  - We present a case of the use of alteplase for the lysis of a large urinary
      bladder clot. A neonate presented with respiratory failure, secondary to a left
      diaphragmatic hernia necessitating the need for extracorporeal membrane
      oxygenation (ECMO) support. On day 3 of ECMO support, hematuria was noted, and a
      subsequent urinary bladder ultrasound revealed a significant urinary bladder
      clot. Alteplase (0.5-1 mg) was instilled into the urinary bladder via a 10 French
      Foley catheter (Sherwood Medical, St. Louis, MO). The catheter was clamped for 1
      hour, followed by irrigation with normal saline. Multiple doses of alteplase were
      administered, resulting in complete resolution of the bladder clot. No adverse
      effects were attributed to the use of the intravesical alteplase. Alteplase seems
      to be safe and effective for the resolution of bladder clots, thereby potentially
      avoiding more invasive surgical procedures.

PMID- 11575840
TI  - Hepatitis B virus infection and the response to erythropoietin in end-stage renal
      disease.
AB  - In patients with end-stage renal disease (ESRD), viral or bacterial infections
      are postulated to abolish or impair response to recombinant erythropoietin
      (Epogen). However, previous reports revealed that response to Epogen among
      hemodialysis patients with a particular viral infection--human immunodeficiency
      virus (HIV)--seems to be variable and is independent of illness severity. To
      further explore the issue of response to Epogen in hemodialysis patients with
      viral infection, we retrospectively studied four patients with hepatitis B virus
      infection over a 3 month period to compare their response to Epogen and
      endogenous erythropoietin levels with those of a control group of patients
      without hepatitis B virus infection. Weekly predialysis hematocrit, and monthly
      serum albumin concentration, transferrin saturation as well as percent reduction
      of urea were obtained from patient records, and mean values were calculated for
      each subject. Mean age of the patients (n = 4) was 63 +/- 7.5 years compared with
      55 +/- 23 years for the control subjects (n = 4)(p = 0.02). The mean hematocrit
      of the study patients was 33.7 +/- 2.8% compared with 34.7 +/- 4.9% in the
      control subjects (p = 0.49), and the mean endogenous erythropoietin level in the
      study patients was 27 +/- 22 mlU/ml compared with 5.7 +/- 1.9 mlU/ml in the
      control group (p = 0.001). The mean dose of thrice weekly Epogen, both at onset
      of the study and when endogenous erythropoietin was measured, was 61 +/- 19 U/kg
      body weight in the patients, compared with 74 +/- 8 U/kg body weight in the
      control subjects (p = 0.002). We conclude that patients with ESRD and hepatitis B
      surface antigenemia respond to Epogen as well as their counterparts without
      hepatitis B virus infection. In addition, patients with hepatitis B surface
      antigenemia have much higher serum levels of endogenous erythropoietin and
      require less exogenous erythropoietin injections than their counterparts.

PMID- 11575841
TI  - Evaluation of a novel vitamin E coated cellulosic membrane hollow fiber dialyzer.

PMID- 11575842
TI  - Molecular mechanisms in neurologic disorders.
AB  - Although many pediatric neurologic disorders, such as epilepsy and mental
      retardation, are the result of a combination of genetic and environmental
      factors, many others are the result of mutations of single genes. Most of these
      single gene traits are inherited in autosomal dominant, autosomal recessive, or X
      linked fashion. The diversity of mutations that are responsible for these
      diseases produces variability in phenotypic expression. However, there are other
      important features of many neurologic disorders that cannot be explained by
      standard models of mendelian inheritance. This review focuses on recently
      described mechanisms, such as genomic imprinting, germline mosaicism,
      mitochondrial inheritance, and triplet repeat expansion. The diagnostic
      evaluation, prognostic significance, and recurrence risk for specific
      neurogenetic disorders is correlated with these underlying disease mechanisms.

PMID- 11575843
TI  - Molecular cytogenetics.
AB  - In the past decade, clinical cytogenetics has undergone remarkable advancement as
      molecular biology techniques have been applied to conventional chromosome
      analysis. The limitations of conventional banding analysis in the accurate
      diagnosis and interpretation of certain chromosome abnormalities have largely
      been overcome by these new technologies, which include fluorescence in situ
      hybridization (FISH), comparative genomic hybridization (CGH), and multicolor
      FISH (M-FISH, SKY, and Rx-FISH). Clinical applications include diagnosis of
      microdeletion and microduplication syndromes, detection of subtelomeric
      rearrangements in idiopathic mental retardation, identification of marker and
      derivative chromosomes, prenatal diagnosis of trisomy syndromes, and gene
      rearrangements and gene amplification in tumors. Molecular cytogenetic methods
      have expanded the possibilities for precise genetic diagnoses, which are
      extremely important for clinical management of patients and appropriate
      counseling of their families.

PMID- 11575844
TI  - Relationships between neurologic disorders and hereditary hearing loss.
AB  - Hearing loss is a common disorder that often has a neurologic etiology. Recently,
      there has been significant progress in the discovery of the genes that cause
      sensorineural hearing loss, and this has led to increased understanding of the
      pathophysiology of both syndromic and nonsyndromic hearing problems. These genes
      cover the range of processes involved in neurologic development and function,
      including structural genes, transcription factors, and tumor suppressors; genes
      involved in signal transduction processes, such as ion homeostasis and
      intracellular transport; and mitochondrial genes responsible for oxidative
      phosphorylation and energy production. Interactions between genes as well as
      between genes and environmental factors have also been documented. Understanding
      of these processes should lead to earlier and more accurate diagnosis and more
      effective treatment for neurologic disorders and hearing loss.

PMID- 11575845
TI  - Genetics of neural tube defects.
AB  - Neural tube defects (NTDs) are common congenital malformations that occur when
      the embryonic neural tube fails to close properly during early development.
      Although multifactorial in origin, NTDs appear to have a strong genetic
      component. Mouse NTD mutants provide useful models for the study of candidate
      genes involved in neural tube development and closure. Because maternal
      nutrition, specifically folate supplementation, is a significant modulator of NTD
      risk, genes involved in folate transport and metabolism are a focus of
      investigation. In addition, transcription factors, as well as genes involved in
      mitosis, actin regulation, and methylation appear to be implicated in the causes
      of NTDs. The heterogeneity of function of candidate genes suggests that
      alterations in multiple developmental pathways may lead to the same clinical
      malformation.

PMID- 11575846
TI  - Inherited epilepsies.
AB  - Epilepsy may be acquired or inherited. At least one half of epilepsy is genetic
      in origin; this figure is likely higher in children regardless of whether
      seizures are generalized or partial. Inherited epilepsies are classified as
      benign, cryptogenic, or symptomatic depending on associated clinical,
      electrographic, and neuroimaging features. To date, genetic mutations in the
      idiopathic inherited epilepsies affect channel function within the central
      nervous system; genes underlying symptomatic epilepsies are more heterogeneous.
      Accurate diagnosis of an inherited epilepsy syndrome provides useful prognostic
      information; it also may help guide diagnostic evaluation, including request for
      specific gene testing. In the near future, the relationship between genetic
      defect and response to specific anticonvulsants may also be better defined.

PMID- 11575847
TI  - Genetic counseling issues in predictive genetic testing for familial adult-onset
      neurologic diseases.
AB  - Genetic counseling is important in any genetic testing situation in order to
      address the various issues related to obtaining a genetic diagnosis.
      Presymptomatic testing for adult-onset neurodegenerative disease, in particular,
      presents a complex counseling scenario. It is imperative to discuss the potential
      impact of test results on patients' family dynamics, insurability and
      employability, family planning, and future health in addition to ascertaining a
      complete understanding of recurrence, inheritance, and testing parameters. The
      Huntington disease presymptomatic testing protocol is well-defined and has been
      used for more than 10 years. These guidelines, which protect both patient and
      provider, can now be applied to other diseases as further presymptomatic testing
      capabilities are realized.

PMID- 11575848
TI  - Message from the president of the American Thyroid Association.

PMID- 11575849
TI  - The protein kinase C pathway inhibits iodide uptake by calf thyroid cells via
      sodium potassium-adenosine triphosphatase.
AB  - The effect of the phorbol esther phorbol myristate acetate (PMA) on iodide uptake
      was studied in primary cultures of calf thyroid cells. PMA caused a dose- and
      time-dependent inhibition of thyrotropin (TSH), forskolin, and db-cAMP
      stimulation, indicating an effect distal to both TSH receptor and cAMP
      generation. No action was found on iodide efflux, indicating a selective
      inhibition of iodide uptake. This inhibition was observed even after 5 minutes of
      incubation, thus excluding a possible genomic action. Bisindolmaleimide (BS), a
      specific inhibitor of the protein kinase C (PKC) pathway, reverted the effect of
      PMA. A similar degree of inhibition of the Na+/K+ adenosine triphosphatase
      (ATPase) and iodide uptake by PMA was found, thus suggesting a link between both
      parameters. These results indicate that the PKC pathway inhibits thyroid iodide
      uptake by an action distal to cAMP generation and probably because of a decrease
      in Na+/K+-ATPase activity.

PMID- 11575850
TI  - A high-sensitivity enzyme-linked immunosorbent assay for serum thyroglobulin.
AB  - A sensitive enzyme-linked immunosorbent assay (ELISA) for measuring serum
      thyroglobulin (Tg) is described. The assay has a functional sensitivity of 0.03
      ng/mL and values obtained in sera from patients with treated differentiated
      thyroid cancer (DTC; n = 24, 17 of whom showed some evidence of recurrence) and
      from healthy blood donors (n = 48) were in agreement with those obtained by Tg
      immunoradiometric assay (IRMA) (functional sensitivity = 0.6 ng/ml) (r = 0.99 and
      0.98 for the two groups, respectively). The Tg levels measured by ELISA in 47 of
      the healthy blood donor sera ranged from 2.3 to 139 ng/ml with 1 serum giving a
      value of 0.03 ng/mL. The mean +/- standard deviation (SD) Tg concentration for
      the healthy blood donors was 20.3+/-23 ng/mL. Studies with a recovery test
      suggest that Tg measurements by ELISA were not always reliable when Tg
      autoantibodies were present. Analysis of samples from 167 patients treated
      successfully for DTC (papillary carcinoma, 94; follicular carcinoma, 73) showed
      that 139 were negative for Tg autoantibodies and of these 106 (76%) had Tg levels
      measurable by ELISA (0.03 ng/mL or greater). In contrast, only 7 (5%) of these
      139 sera had Tg levels measurable by IRMA (0.6 ng/mL or greater). It is possible
      that this ability to measure Tg simply and easily in most treated DTC patients
      will have significant advantages for patient care. In particular, the Tg level
      after initial ablative treatment will usually be measurable rather than
      undetectable. Furthermore, any increases in serum Tg levels which may herald
      relapse will be detectable earlier.

PMID- 11575852
TI  - Expression of intracellular adhesion molecule-1 and vascular cell adhesion
      molecule-1 and homing factor CD44 after engraftment of Graves' lymphocytes in
      xenotransplanted human thyroid tissue in athymic nude mice.
AB  - The expression of adhesion molecules on thyrocytes and endothelium cells plays an
      important role in the pathogenesis of Graves' disease (GD). The intercellular
      adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule-1 (VCAM-1), and
      the homing receptor CD44 are responsible for the specific migration of
      lymphocytes in autoimmune thyroid diseases (AITD) (homing). Eight weeks after
      transplantation of thyroid tissue from 26 patients with nonautoimmune thyroid
      disease (nontoxic nodular goiter [NTG]) into nude mice, peripheral (PBL) and
      intrathyroidal lymphocytes (ITL) from 14 patients with NTG and 12 patients with
      GD were grafted into the animals. Two days after lymphocyte engraftment, the
      thyroid transplants were examined histologically (HE) and immunohistologically
      stained with monoclonal antibodies directed against ICAM-1, VCAM-1, and CD44.
      After injection of GD lymphocytes, thyroid transplants expressed significantly
      more ICAM-1, VCAM-1, and CD44 than after injection of NTG lymphocytes. This
      expression was even more pronounced after grafting of GD intrathyroidal
      lymphocytes. Our data demonstrate that only GD lymphocytes induce the expression
      of adhesion molecules and homing factor CD44, both of which play an important
      role in the migration of lymphocytes and induction of the autoimmune process.

PMID- 11575851
TI  - Sodium iodide symporter and pendrin expression in human thyroid tissues.
AB  - Thyroid cells synthesize thyroid hormones through a multistep process during
      which iodide is transported through the basolateral and the apical membranes of
      thyrocytes. Two genes that participate in these transports and the corresponding
      proteins, namely sodium iodide symporter (NIS) and pendrin, the product of the
      Pendred syndrome gene, have recently been characterized. We studied NIS and
      pendrin expression at the mRNA and protein levels by a quantitative reverse
      transcription-polymerase chain reaction (RT-PCR) method and by single and double
      immunostaining in normal and pathological human thyroid tissues. In normal
      tissue, NIS and pendrin were detected in about 20% and 40%-60% of thyrocytes,
      respectively. The number of NIS- and pendrin-positive cells was much higher in
      hyperfunctioning tissue from Graves' disease or toxic adenoma. In hypofunctioning
      adenomas and carcinomas, the number of NIS- and pendrin-positive cells was low or
      nonexistent. Three types of follicular cells were observed in positive tissues:
      NIS-negative/pendrin-negative cells, NIS-positive/pendrin-positive cells, and NIS
      negative/pendrin-positive cells. The first two types of cells appear to be
      resting and active cells, respectively, but the functional status of NIS
      negative/pendrin-positive thyrocytes remains to be determined.

PMID- 11575853
TI  - Sodium iodide symporter-based strategies for diagnosis and treatment of thyroidal
      and nonthyroidal malignancies.
AB  - The recent cloning and molecular characterization of the sodium iodide-symporter
      (NIS) has inspired novel approaches to the diagnosis and treatment of thyroidal
      and nonthyroidal malignancies. This article briefly reviews the physiologic
      regulation of NIS expression by cytokines, the expression in benign and malignant
      thyroidal diseases, and the expression in extrathyroidal tissues. Current
      concepts for NIS-based cancer therapy in thyroidal and extrathyroidal tumors are
      presented. The recent discovery of NIS expression in a majority of breast cancers
      as well as its promising application for prostate cancer imply potential
      applications in diagnostic imaging and radioiodine anticancer therapy for these
      highly common and lethal malignancies.

PMID- 11575854
TI  - The Sardinian Autoimmunity Study: 3. Studies on circulating antithyroid
      antibodies in Sardinian schoolchildren: relationship to goiter prevalence and
      thyroid function.
AB  - The relationship among iodine intake, goiter prevalence, and thyroid autoimmunity
      remains controversial. In the present article, we report the prevalence of
      antithyroid antibodies (ATA) in relation to iodine intake, frequency of goiter,
      and thyroid function in a large group of Sardinian schoolchildren living in areas
      with borderline iodine sufficiency, or mild to moderate iodine deficiency. A
      total of 8,040 schoolchildren (4,194 males, 3,846 females, ages 6-15 years) from
      29 communities were examined between 1986-1994. Thyroid size was assessed by
      palpation, according to the Pan American Health Organization (PAHO) criteria. In
      all cases antimicrosomal (MAb) or antithyroid peroxidase antibodies (TPOAb) and
      thyrotropin (TSH) were assayed. Urinary iodine was determined in a subgroup of
      820 children. ATA was detected in 235 (2.92%) sera (88 males, 2.12%; 147 females,
      3.82%; chi2 = 20.41, p < 0.0001). ATA prevalence ranged between 0.0%-7.3% in the
      29 communities without any geographical correlation with goiter prevalence and
      urinary iodine excretion. However, ATA was more frequently detected in goitrous
      children, especially in females. The presence of ATA was not age-dependent in
      males, whereas a significant increase of ATA was observed in females older than
      11 years of age. Seventy-seven (0.96%) children showed borderline to slightly
      increased serum TSH (>5.2-32 mU/L). Increased serum TSH concentration was more
      frequently found in children with ATA, especially at higher titers. In summary,
      our study in Sardinian schoolchildren indicates: (1) ATA display geographical
      heterogeneity, which seems to be unrelated to goiter prevalence and/or to iodine
      supply; (2) ATA are more frequently detected in females older than 11 years of
      age, suggesting that puberty has a role in determining the predominance in
      females of thyroid autoimmunity; (3) although most goitrous children are ATA
      negative, the prevalence of ATA is increased in children with enlarged glands;
      (4) ATA is associated with an increased prevalence of subclinical hypothyroidism.

PMID- 11575855
TI  - Immunostaining for ret oncogene proteins in papillary thyroid carcinoma: a
      correlation of ret immunoreactivity and potential of lymph node metastasis.
AB  - Ret oncogenes, particularly Ret/PTC, have been associated with the potential of
      local invasion of papillary thyroid carcinoma (PTC). The purpose of this study
      was to investigate the correlation between the Ret oncogene expression and the
      potential of lymph node metastasis of PTC. A total of 107 PTC were
      microscopically reviewed to identify areas of infiltrating carcinoma (IC). IC was
      defined as tumor cells disposed in a haphazard pattern and in lobules, nests,
      follicles, or single cells within a desmoplastic or sclerotic stroma. All cases
      were submitted to immunostaining for Ret oncogene. There were 36 noninfiltrating
      PTC with lymph node metastasis in 1 case and 71 infiltrating PTC with lymph node
      metastasis in 40 cases. For non-PTC, the positive immunoreactivity was often weak
      to moderate and focal. For infiltrating PTC with IC, the IC displayed strong
      immunoreactivity. The noninfiltrating component of PTC with IC usually showed
      stronger reactivity than PTC without an infiltrating component. Furthermore, 36
      of 40 metastatic PTC in lymph node were immunoreactive. Three follicular adenomas
      with areas of scar caused by fine-needle aspiration biopsy were not
      immunoreactive for Ret. In view of the high potential of infiltrating PTC for
      lymph node metastasis, distinction of this type of carcinoma from its
      noninfiltrating form is clinically important. Because immunoreactivity for Ret is
      usually positive in areas of infiltrating PTC and is often negative or focally
      positive in noninfiltrating PTC, immunostaining for Ret is helpful to identify
      infiltrating PTC and distinguish it from changes caused by fine-needle aspiration
      biopsy in benign thyroid lesions.

PMID- 11575856
TI  - Radioiodine ablation of thyroid remnants after preparation with recombinant human
      thyrotropin.
AB  - Radioiodine ablation (RA) of normal thyroid remnants after thyroidectomy for
      differentiated thyroid carcinoma improves the sensitivity of subsequent
      radioiodine scans and serum thyroglobulin measurements for detection of residual
      thyroid carcinoma. Local cancer recurrences are also lower after RA. One standard
      preparation for RA involves rendering the patient hypothyroid in order to
      stimulate endogenous thyrotropin (TSH) secretion and sodium iodide symporter
      (NIS) activity. An alternative approach is to prescribe thyroxine after
      thyroidectomy and to stimulate NIS with exogenous recombinant human thyrotropin
      (rhTSH). This latter approach was used in 10 patients at our medical center.
      Complete resolution of all visible 131I thyroid bed uptake was achieved in all
      when follow-up scans were performed 5 to 13 months later. This approach has the
      potential to successfully ablate thyroid remnants without the need to induce
      hypothyroidism.

PMID- 11575857
TI  - Thyroxine and illness severity in very low-birth-weight infants.
AB  - The objective of this study was to determine the relationship between thyroxine
      (T4) and illness severity in a population of preterm infants. We investigated a
      cohort of infants with birth weights 1,500 g or less from a single level III
      neonatal intensive care unit who received a minimum of one cranial sonogram to
      screen for intraventricular hemorrhage (IVH) and one newborn screen for T4 during
      a 2-year period, (n = 284). The Score for Neonatal Acute Physiology (SNAP) was
      used to measure illness severity. T4 and SNAP were investigated in relationship
      to mortality, IVH, and severe IVH. T4 correlated inversely with SNAP (R = -0.46,
      p < 0.01). Infants with severe IVH and mortality had lower T4 and higher SNAP
      scores when compared to infants without these conditions. These differences
      persisted after controlling for the confounding effect of gestational age.
      Analysis of receiver operator curves indicated that high SNAP and low T4 were
      equivalently associated with IVH, severe IVH, and mortality. Our data indicate
      that T4 is associated with illness severity in very low-birth-weight infants. Low
      T4 levels and high SNAP scores are both associated with the outcomes of IVH and
      mortality in very low-birth-weight infants.

PMID- 11575858
TI  - Contralateral papillary thyroid cancer is frequent at completion thyroidectomy
      with no difference in low- and high-risk patients.
AB  - Total (or near-total) thyroidectomy (TT) is considered by many as the most
      adequate treatment for papillary thyroid carcinoma (PTC). In patients who have
      undergone lobectomy, the necessity of performing a completion thyroidectomy (CT)
      is still discussed. The aim of this retrospective study was to evaluate tumor
      bilaterality in patients initially treated with partial thyroidectomy for PTC and
      who then underwent CT. We studied 182 patients treated with CT after lobectomy
      and/or isthmectomy for PTC diagnosed from 1969-1998. Mean age at diagnosis was
      40+/-14.5 years and mean interval between partial thyroidectomy and CT was 19.8+/
      56.8 months. At CT, 80 of 182 patients (44%) had one or more foci of tumor in the
      remaining thyroid lobe, always of the same papillary histotype, associated with
      ipsilateral lymph node metastases in 22 cases. In addition, 10 patients with no
      tumoral foci in the thyroid specimen had evidence of lymph node metastases. The
      rate of bilateral tumor was not different when patients were analyzed according
      to the classification of "low-" or "high-risk." Among several clinical features,
      the presence of lymph node metastases at the first surgical treatment and time
      interval between first treatment and CT were correlated with higher frequency of
      bilaterality (p = 0.033 and p = 0.044, respectively). The postsurgical 131I whole
      body scan revealed the presence of persistent lymph node metastases or diffuse
      micronodular lung metastases in 7 and 6 patients, respectively. In conclusion,
      PTC was frequently bilateral in our series and this bilaterality was independent
      from the "low-" or "high-risk" classification. On these bases, we believe that
      PTC should be treated with TT when diagnosed before surgery and submitted to CT,
      if partial surgery was the initial intervention.

PMID- 11575859
TI  - Severe thyrotoxicosis induced by thyroid metastasis of lung adenocarcinoma: a
      case report and review of the literature.
AB  - A 50-year-old woman who had undergone lung lobectomy because of lung
      adenocarcinoma presented with thyrotoxicosis, neck swelling, and cervical
      lymphadenopathy one month after the operation. The total serum triiodothyronine
      (T3) and thyroxine (T4) levels were markedly elevated to 514 ng/dL and 26.4
      microg/dL, respectively, and serum thyrotropin (TSH) was suppressed to less than
      0.005 microU/mL. Although the thyroid gland had been normal before surgery, chest
      computed tomography (CT) scan revealed a markedly enlarged thyroid gland only 1
      month after surgery. 123I uptake for 24 hours was suppressed to 4% in the thyroid
      gland with no uptake elsewhere including the lung. Fine-needle aspiration
      cytology (FNAC) of the thyroid showed invasion of poorly differentiated
      adenocarcinoma cells, cytologically identical to the cells obtained from sputum
      and those infiltrating the resected sections of the lung adenocarcinoma.
      Immunohistochemical studies of resected lung tissues did not show positive
      staining for thyroglobulin, carcinoembryonic antigen (CEA), or surfactant protein
      A. Clinically, the thyrotoxicosis had spontaneously improved, followed by a
      hypothyroid state with shrinkage of the thyroid gland after chemotherapy. Despite
      repeated chemotherapy and the administration of thyroxine for hypothyroidism, the
      patient died of respiratory failure 9 months after the onset of thyrotoxicosis.
      From these findings and the clinical course, thyroid metastasis, developing
      subacutely from lung adenocarcinoma, was diagnosed. We speculate that aggressive
      invasion of tumor cells into the thyroid gland resulted in highly destructive
      thyrotoxicosis.

PMID- 11575860
TI  - Malignant struma ovarii: an unusual presentation.
AB  - Malignant struma ovarii is a rare disease; only a few cases are well documented
      in the literature. Thus, the overall prognosis and modalities of treatment are
      still somewhat controversial. In this article, the authors report a case of
      malignant struma ovarii discovered 4 years after ovariectomy after metastasis to
      the lungs and bones. Review of the pathology of the ovarian struma did not reveal
      the classic criteria of malignancy, there were, however, many features considered
      to be atypical and thus suspicious. The patient was treated by total
      thyroidectomy followed by repetitive doses of 131I. However, because of
      difficulties in increasing the level of endogenous thyrotropin (TSH) because of
      functional thyroid metastases in such an advanced disease, recombinant human
      thyrotropin (rhTSH; Thyrogen, thyrotropin alpha, Genzyme Corporation, Cambridge,
      MA) was used before administration of radioiodine. With this therapeutic
      protocol, the patient is still clinically stable 2 years after diagnosis.

PMID- 11575861
TI  - Hashimoto's thyroiditis presenting as a functioning adenoma.

PMID- 11575862
TI  - Myasthenia gravis.

PMID- 11575863
TI  - The spinocerebellar ataxias.
AB  - The spinocerebellar ataxias (SCAs) are diseases characterized by the progressive
      degeneration and subsequent loss of neurons accompanied by reactive gliosis,
      degeneration of fibers from the deteriorating neurons, and clinical symptoms
      reflecting the locations of the lost neurons. The degenerative changes affect
      specific neuronal groups while others remain preserved, and these diseases can
      therefore be viewed as system degenerations. The SCAs result from either
      genetically transmitted diseases with dominant inheritance or unknown causes with
      sporadic occurrence. Most of these disorders affect the cerebellum and its
      pathways, resulting in progressive deterioration of cerebellar function
      manifested by increasing unsteadiness of gait, incoordination of limb movements
      with impairment of skilled movements such as handwriting, and a distinctive
      dysarthria. Other neuronal systems are affected in some of these disorders,
      notably the corticospinal pathway, basal ganglia, and autonomic nuclei of the
      brain stem and spinal cord.

PMID- 11575864
TI  - Dynamic and kinetic effects of chronic citalopram treatment in experimental
      hepatic encephalopathy.
AB  - Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome that arises in
      liver-impaired subjects. Patients with HE display various neuropsychiatric
      symptoms including affective disturbances and may therefore likely receive
      treatment with novel thymoleptics like citalopram (CIT). The simultaneous
      pharmacokinetic and pharmacodynamic outcome of the commonly used serotonin
      selective thymoleptic drugs in liver-impaired subjects with pending chronic HE is
      far from understood today. We therefore investigated the effects of chronic, body
      weight-adjusted (10 mg x kg(-1) x day(-1)), treatment with CIT in rats with and
      without portacaval shunts (PCS). Open-field activity was monitored. The 5-HT, 5
      HIAA, noradrenaline (NA), and dopamine (DA) output were assessed in the frontal
      neocortex. The racemic levels of CIT and its metabolites DCIT and DDCIT,
      including the S- and R-enantiomers, were determined in serum, brain parenchyma,
      and extracellular fluid. The rats with PCS showed higher (2-3-fold) levels of CIT
      than rats undergoing a sham treatment with CIT in all compartments investigated.
      The PCS rats also showed elevated levels of DCIT and DDCIT. No major differences
      in the S/R ratios between PCS rats and control rats could be detected. The CIT
      treatment resulted in neocortical output differences between PCS rats and control
      rats mainly within the 5-HT and DA systems but not within the NA system. For the
      5-HT system, this change was further evidenced by outspoken elevation in 5-HT
      output after KCI-depolarizing challenges. Moreover, the CIT treatment to PCS rats
      was shown to "normalize" the metabolic turnover of 5-HT, measured as a profound
      lowering of a basal elevation in the 5-HIAA levels. The CIT treatment resulted in
      an increased or "normalized" behavioral activity in the PCS group. Therefore, a
      dose-equal chronic treatment with CIT in PCS rats produced pharmacokinetic and
      pharmacodynamic changes not observed in control rats. The results further support
      the contention of an altered 5-HT neurotransmission prevailing in the chronic HE
      condition. However, the tentatively beneficial behavioral response also seen
      following chronic CIT treatment to PCS rats in this study has to be viewed in
      relation to both the pharmacokinetic and pharmacodynamic changes observed.

PMID- 11575865
TI  - Cations of cisternal cerebrospinal fluid in humans and the effect of different
      doses of nimodipine on CSF calcium after stroke.
AB  - Cisternal samples of cerebrospinal fluid (CSF) were analyzed for protein,
      albumin, sodium (Na), potassium (K), and calcium (Ca) content in 21 control
      subjects and 64 patients who had experienced acute stroke. A second cisternal CSF
      sample was taken in 37 of the stroke patients after 2-3 weeks treatment with the
      calcium antagonist nimodipine. Increased permeability of the blood-brain barrier
      was reflected by the significantly higher CSF/serum ratio of albumin in stroke
      patients than in control subjects (0.0046 vs. 0.0028,p = 0.0012). Serum and CSF
      concentrations of Na, K, and Ca did not differ between control subjects and
      stroke patients. In control subjects and in stroke patients, concentration of
      calcium in cisternal CSF ([Ca]) was smaller than values reported by others in
      lumbar samples. In stroke patients, the pH of CSF was lower than that of
      simultaneously taken blood (7.38 vs. 7.44, p < 0.001). No differences between
      stroke patients and control subjects were found for the cisternal CSF/serum
      ratios of Na (1.0 and 0.99), K (0.61 and 0.63), and Ca (0.25 and 0.24). When
      patients and controls were pooled together, CSF total [Ca] correlated weakly with
      serum total [Ca] (Spearman r = 0.28, p = 0.014) and with serum ionized [Ca]
      (Spearman r = 0.27, p = 0.016). After 2-3 weeks of nimodipine treatment, CSF [Ca]
      was significantly lower in the subgroup treated with 60 mg nimodipine four times
      daily (240 mg/d) than with 30 mg four times daily. A nimodipine dosage of 30 mg
      four times daily (120 mg/d) did not affect CSF [Ca]. A 240 mg daily dosage, but
      not a 120 mg daily dosage, of nimodipine may affect the Ca transport system in
      humans at the choroid plexus.

PMID- 11575866
TI  - Rasagiline mesylate, a new MAO-B inhibitor for the treatment of Parkinson's
      disease: a double-blind study as adjunctive therapy to levodopa.
AB  - Rasagiline mesylate (TVP-1012) is a potent, selective, non-reversible MAO-B
      inhibitor, without the tyramine-potentiating effect and with neuroprotective
      activities. The benefit of rasagiline as monotherapy in patients with early
      Parkinson's disease (PD) has already been reported. To evaluate the safety,
      tolerability, and clinical effect of rasagiline as adjunctive therapy to
      levodopa, a multicenter, double-blind, randomized, placebo-controlled, parallel
      group study (0.5, 1, and 2 mg/d) was conducted for 12 weeks in 70 patients with
      PD (mean age, 57.4 y; mean disease duration, 5.7 y; 32 patients had motor
      fluctuations). A beneficial clinical effect was observed in fluctuating patients
      treated with rasagiline (all doses), expressed as a decrease in total Unified
      Parkinson's Disease Rating Scale (UPDRS) score (23.0% vs 8.5% in the placebo
      group). The treatment effect was still evident 6 weeks after drug discontinuation
      (in all doses). The safety and tolerability of rasagiline were good. Adverse
      events were no different than those of patients taking placebo. Almost complete
      platelet MAO-B inhibition was obtained at all rasagiline doses. This study has
      demonstrated that rasagiline (up to 2 mg/day) has a good safety profile and a
      beneficial clinical effect in fluctuating patients with PD when given as an add
      on to chronic levodopa therapy.

PMID- 11575867
TI  - Cognitive and motor function in patients with Parkinson's disease with and
      without depression.
AB  - The objective of this study was to define risk factors for depression in patients
      with idiopathic Parkinson's disease (PD) and to evaluate the correlation of
      depression with cognitive function and the primary domains of parkinsonian motor
      dysfunction tremor, bradykinesia, rigidity, gait and balance impairment. The risk
      factors for depression in patients with PD remain controversial. Several
      investigators have demonstrated a significant association between cognitive
      dysfunction and depression, but motoric and disease variables can confound this
      evaluation and have shown an inconsistent relation to depression. A consecutive
      series of 88 patients with PD were examined using the motor subscale of the
      Unified Parkinson's Disease Rating Scale (UPDRSm), Hoehn-Yahr stage (HY), and
      Hamilton Rating Scale for Depression (HRSD). Major depression was diagnosed
      according to the criteria in the Diagnostic and Statistic Manual of Mental
      Disorders, 4th edition. Gender, age, handedness, PD duration, side of PD onset,
      motor fluctuations, UPDRSm total score, daily Levodopa dose, and Mini-Mental
      State Examination score (MMSE) were analyzed using multivariate and univariate
      logistic regression, Fisher's Exact test, and Pearson correlations. Major
      depression was diagnosed in 12 patients (7.3%). Low MMSE score, axial
      bradykinesia, gait and balance impairment were strongly significant predictors of
      depression. In conclusion, depression and physical function are important factors
      impairing the quality of life for patients with PD, and regular depression
      screening and treatment should focus on patients with PD who have cognitive
      impairment, high axial bradykinesia, gait and balance impairment.

PMID- 11575868
TI  - Risperidone in the treatment of psychotic depression.
AB  - Risperidone has been primarily marketed for the treatment of schizophrenia. There
      are reports about its potential role for the treatment of affective illness. We
      report here another case of a patient with psychotic depression who was treated
      successfully with risperidone as monotherapy. This case report suggests that
      risperidone can be an efficient treatment mode for psychotic depression; however,
      it needs more data based on controlled study.

PMID- 11575869
TI  - Orofacial effects of antiretroviral therapies.
AB  - This paper summarises some of the oral adverse effects of antiretroviral agents.
      Some are related to bone marrow suppression which may also predispose to mouth
      ulcers. Erythema multiforme and toxic epidermal necrolysis are especially well
      recognized in HIV disease, particularly as reactions to sulphonamides and to
      antiretroviral agents. Oral lichenoid reactions have been described in HIV
      disease often relating to zidovudine use. Didanosine has also produced erythema
      multiforme and not unusually induces xerostomia, again by an unknown mechanism.
      Xerostomia may be seen in up to one-third of patients taking didanosine. Taste
      abnormalities are common with the protease inhibitors and oral and perioral
      paraesthesia can be a disturbing adverse effect. Ritonavir in particular can give
      rise to circumoral paraesthesia in over 25% of patients. Indinavir can also
      produce cheilitis.

PMID- 11575870
TI  - Inhalational and topical steroids, and oral candidosis: a mini review.
AB  - Candidosis is by far the commonest oral fungal infection in man and could
      manifest as an adverse effect of drug therapy such as inhaled or topically
      applied corticosteroids. Due to the anti-inflammatory and immunosuppressive
      effect steroids are used in the management of bronchial asthma and oral mucosal
      diseases. In this mini review we discuss the clinical and laboratory findings on
      the relationship between steroid inhalers, other topical steroids and oral
      candidosis, possible mechanisms of pathogenicity following such therapy as well
      as the precautions that could be taken to minimize this adverse side effect.

PMID- 11575871
TI  - Exfoliative cytology: a helpful tool for the diagnosis of paracoccidioidomycosis.
AB  - OBJECTIVE: To describe the main cytological findings associated with smears
      collected from oral lesions of paracoccidioidomycosis and to appraise the use of
      cytology as a diagnostic tool for the disease. STUDY DESIGN: Cytological smears
      and biopsies were collected from 40 lesions with a clinical suspicion of
      paracoccidioidomycosis. Evaluation of the sensitivity, specificity, positive and
      negative predictive values, accuracy and the positive likeness ratio of the oral
      smear when compared with the histological diagnosis, was performed. The latter is
      considered the 'gold standard' for comparison. RESULTS: The main morphological
      findings were the rounded-shaped, birefringent and multiple-budded fungi,
      Langhans' giant cells and epithelioid cells. The following associative measures
      were found: sensitivity, 67.9%; specificity, 91.7%; positive predictive value,
      95.0%; negative predictive value, 55.0%; accuracy, 75.0%; and positive likeness
      ratio, 8.14. CONCLUSION: The cytological findings of paracoccidioidomycosis are
      characteristic and cytology is accurate in the diagnosis of the disease. Positive
      patients should be treated. Negative patients should be submitted to biopsy to
      confirm or to dismiss the diagnosis of this mycosis.

PMID- 11575872
TI  - LongoVital and herpes labialis: a randomised, double-blind, placebo-controlled
      study.
AB  - OBJECTIVE: LongoVital (LV) (DK. Reg. No. 5178/75) is a herbal-based tablet
      enriched with the recommended daily doses of vitamins. The present study was
      undertaken to investigate possible prevention of recurrent herpes labialis (RHL)
      during 4 months' daily intake of LV. DESIGN: Placebo-controlled, double-blind,
      randomised, clinical trial. SUBJECTS: Fifty-two patients with a minimum of 4
      yearly HL episodes. METHODS: The patients were given either LV or placebo for 4
      months and followed-up for another 4 months. The number, duration and maximal
      size of lesions were assessed. RESULTS: Twenty-seven patients (Group A) received
      LV and 25 patients placebo (Group B). There were no statistically significant
      differences between Group A and Group B with respect to number, duration and size
      of lesions. Within Group A, however, there was a decrease in all three parameters
      after 2 months' intake of LV (P < 0.05). The decrease in the number of HL
      episodes in Group A lasted during the entire follow-up period (P < 0.05). At the
      end of the medication period, significantly more patients in Group A than in
      Group B assessed the number and duration of recurrences to be reduced compared
      with before the trial (P < 0.05). CONCLUSION: LV was not superior to placebo in
      the prevention of RHL although subjective assessment was in favour of LV, and the
      LV group had less episodes after 2 months on the tablets.

PMID- 11575873
TI  - Oligodontia is associated with extra-oral ectodermal symptoms and low whole
      salivary flow rates.
AB  - INTRODUCTION: Ectodermal dysplasias (EDs) involve abnormal development of hair,
      teeth, nails, and sweat glands. OBJECTIVES: (1) To investigate the frequency of
      extraoral ectodermal symptoms in persons with oligodontia (>6 congenitally
      missing teeth). (2) To examine whole salivary flow rates in oligodontia patients,
      with special emphasis on persons with EDs. SURVEY GROUP AND METHODS: Sixty-eight
      persons with oligodontia and 39 healthy control persons were included. All
      participants underwent an interview, general and oral examinations, and whole
      salivary secretory tests. RESULTS: Thirty-nine (57%) of the oligodontia patients
      had disturbances in either hair, nails and/or sweat production in addition to
      teeth and were classified as the ED group. The remaining 29 oligodontia patients
      had no obvious signs of EDs (non-ED group). The prevalences of dry skin, asthma
      and eczema were higher, and whole salivary secretory rates lower, in the ED group
      as compared to the control group. Intermediate values were observed in the non-ED
      group. Incisors, canines and molars were more frequently missing in the ED group
      than in the non-ED group, whereas no differences were observed in the frequency
      of missing premolars. Negative correlations between the number of missing teeth
      and unstimulated and chewing stimulated whole salivary secretory rates were
      found.

PMID- 11575874
TI  - Effect of Actinobacillus actinomycetemcomitans protease on the proliferation of
      gingival epithelial cells.
AB  - OBJECTIVE: Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) has
      been implicated as an important pathogen in periodontal disease. The aim of this
      report is to examine the effect of in vitro application of A.
      actinomycetemcomitans protease on the cell growth, DNA synthesis, and fibronectin
      level of human gingival epithelial cells. MATERIALS AND METHODS: A.
      actinomycetemcomitans protease was isolated from the culture supernatant of A.
      actinomycetemcomitans. Human gingival epithelial cells were incubated in the
      presence or absence of A. actinomycetemcomitans protease (0.01, 0.1, or I U) for
      48 h. The proliferation of cells were tested with the MTT assay and the BrdU
      assay. The fibronectin level was examined by flow cytometric analysis. RESULTS:
      The cell growth rate, DNA synthesis rate, and fibronectin level of the gingival
      epithelial cells that had been incubated with protease, were lower than the
      respective values in the untreated gingival epithelial cells; as the dose of A.
      actinomycetemcomitans protease increased, the cell growth rate, DNA synthesis
      rate, and fibronectin level of the gingival epithelial cells decreased. A.
      actinomycetemcomitans protease may inhibit the proliferation of human gingival
      epithelial cells. CONCLUSIONS: This protease may play a key role as a major
      virulence factor in the development of periodontal disease.

PMID- 11575875
TI  - The roles of the N-terminal portions of various tachykinins in promoting
      salivation.
AB  - OBJECTIVES: In order to determine the active sites for salivation of various
      tachykinins, the regulatory roles of the N-terminal portion of various newly
      synthesized tachykinins were studied after i.p. injection of rats using the
      submandibular glands as model organs. METHODS: N-shortened oligopeptides from
      kassinin, eledoisin, neurokinins A (NKA) and NKB were synthesized by the multipin
      peptide synthesis method. Amino acids were eliminated one by one to form octa- to
      undeca-peptides adjoining the inactive or less active heptapeptides and various
      heptapeptides, in which an amino acid in position 8 (Xaa8), numbering as in an
      undecapeptide, was replaced with Tyr, Phe, Ile or Val. RESULTS: The N-terminal
      amino acids in positions 1 to 4 could be activators or inhibitors, depending on
      whether the C-terminal heptapeptide was inactive or less active. The Xaa8
      residue, in combination with amino acids in positions 5 and 6, seemed to be very
      important in determining the sialogogic activity of a heptapeptide. The
      discrimination between NKA and NKB appeared due to the N-terminal amino acid
      sequence in positions I to 4 including Phe or Ser in position 6. CONCLUSIONS: It
      is concluded that the N-terminal amino acids in positions I to 4 serve as either
      activators or inhibitors depending upon the sialogogic activity of the C-terminal
      heptapeptide, in which particular amino acids in positions 5, 6 and 8 regulate
      its activity.

PMID- 11575876
TI  - Mast cell degranulation and the role of T cell RANTES in oral lichen planus.
AB  - OBJECTIVES: The present study investigated mast cell degranulation in oral lichen
      planus (OLP) and the effect of OLP lesional T cell supernatants on mast cell
      degranulation. MATERIALS AND METHODS: Immunohistochemistry was used to identify
      mast cell degranulation in both OLP (n = 22) and normal control (n = 14) tissues.
      OLP lesional T cell lines (n = 5) and HMC-1 (a human leukemia mast cell line)
      were used to examine the effects of OLP T cell supernatants on mast cell
      degranulation in vitro. RESULTS: Approximately 60% of mast cells were
      degranulated in OLP. OLP lesional T cells expressed mRNA for RANTES, and TNF
      alpha stimulation upregulated OLP lesional T cell RANTES secretion. OLP lesional
      T cell supernatants induced degranulation of HMC-1 with release of TNF-alpha and
      histamine. Human recombinant RANTES similarly induced mast cell degranulation.
      Anti-RANTES antibody blocked OLP lesional T cell supernatant-induced mast cell
      degranulation. CONCLUSIONS: This study is the first to show that OLP lesional T
      cells produce and secrete RANTES which triggers human mast cell degranulation.
      Degranulating mast cells release TNF-alpha which upregulates OLP lesional T cell
      RANTES secretion. Such a cyclical mechanism may underlie disease chronicity and
      future therapies may include blocking RANTES or TNF-alpha activity in OLP.

PMID- 11575877
TI  - Permeability barrier properties of oral keratinocyte cultures: a model of intact
      human oral mucosa.
AB  - OBJECTIVES: The aim of this study was to establish whether an in vitro model of
      human oral mucosa had similar permeability characteristics to normal oral mucosa.
      Such a model would have considerable value as an alternative to the use of
      mucosal biopsies in studies of transmucosal drug delivery. MATERIALS AND METHODS:
      Keratinocytes obtained from buccal mucosa, hard palate and abdominal skin were
      seeded onto inert collagen membranes (Cellagen Discs) or dead de-epidermised
      dermis (DDED) and grown either as submerged or air-liquid interface cultures.
      Subsequently the ultrastructural characteristics, permeability to water and
      barrier lipid content of the epithelial cultures were assessed and compared with
      samples of intact mucosa and skin. RESULTS: All the cultures stratified into
      multilayered epithelia and displayed features of differentiation including
      tonofilaments, desmosomes and membrane coating granules. The permeability
      characteristics and barrier lipid content of the oral mucosal cultures resembled
      those of intact mucosa. By contrast, epidermal keratinocytes failed to produce a
      permeability barrier comparable with that of skin and had low levels of barrier
      associated lipids. CONCLUSIONS: Cultures of human oral mucosal keratinocytes
      obtained from healthy adults develop similar permeability properties and barrier
      lipid composition to their site of origin. This model system may be useful for
      the evaluation of local and systemic oral mucosal drug delivery.

PMID- 11575878
TI  - Implantation of octacalcium phosphate nucleates isolated bone formation in rat
      skull defects.
AB  - OBJECTIVE: Our previous radiographic examinations have indicated that the
      synthetic octacalcium phosphate (OCP) may provide the core for nucleating
      multiple osteogenic sites in the experimentally created cranial defect. DESIGN:
      The present study was designed to confirm the possibility that the implanted OCP
      causes the osteoinduction as well as the osteoconduction in the rat cranial
      defect. MATERIALS AND METHODS: Standardized defects were created in male Wistar
      rat calvaria, and the OCP granules were implanted into the defect. The sham
      operated rats were processed in the same way except that nothing was implanted.
      The rats were fixed at 4 weeks after implantation of OCP or the sham operation.
      We examined bone formed on the implanted OCP, analyzing serial sections
      histologically combined with immunohistochemistry for the bone specific protein,
      osteocalcin. RESULTS: In the defects treated with OCP, the radiopacity was
      scattered throughout the defect besides being observed along the defect margin of
      the parietal bone. Examination of the serial sections showed that some of new
      bones on the implanted OCP were formed away from the defect margin of the
      parietal bone with regard to both histological identification and specific
      molecular marker. CONCLUSIONS: The present study suggested that the implanted OCP
      can serve as a core for initiating bone formation and cause the osteoinduction as
      well as the osteoconduction in the defect.

PMID- 11575879
TI  - Diesel engines: environmental impact and control.

PMID- 11575880
TI  - The influence of human activity patterns on personal PM exposure: a comparative
      analysis of filter-based and continuous particle measurements.
AB  - Particulate matter (PM) exposure data from the U.S. Environmental Protection
      Agency (EPA)-sponsored 1998 Baltimore and 1999 Fresno PM exposure studies were
      analyzed to identify important microenvironments and activities that may lead to
      increased particle exposure for select elderly (>65 years old) subjects.
      Integrated 24-hr filter-based PM2.5 or PM10 mass measurements [using Personal
      Environmental Monitors (PEMs)] included personal measurements, indoor and outdoor
      residential measurements, and measurements at a central indoor site and a
      community monitoring site. A subset of the participants in each study wore
      passive nephelometers that continuously measured (1-min averaging time) particles
      ranging in size from 0.1 to approximately 10 microm. Significant activities and
      locations were identified by a statistical mixed model (p < 0.01) for each study
      population based on the measured PM2.5 or PM10 mass and time activity data.
      Elevated PM concentrations were associated with traveling (car or bus),
      commercial locations (store, office, mall, etc.), restaurants, and working. The
      modeled results were compared to continuous PM concentrations determined by the
      nephelometers while participants were in these locations. Overall, the
      nephelometer data agreed within 6% of the modeled PM2.5 results for the Baltimore
      participants and within approximately 20% for the Fresno participants
      (variability was due to zero drift associated with the nephelometer). The
      nephelometer did not agree as well with the PM10 mass measurements, most likely
      because the nephelometer optimally responds to fine particles (0.3-2 microm).
      Approximately one-half (54 +/- 31%; mean +/- standard deviation from both
      studies) of the average daily PM2.5 exposure occurred inside residences, where
      the participants spent an average of 83 +/- 10% of their time. These data also
      showed that a significant portion of PM2.5 exposure occurred in locations where
      participants spent only 4-13% of their time.

PMID- 11575881
TI  - A 13-week comparison of passive and continuous ozone monitors at forested sites
      in north-central Pennsylvania.
AB  - Ogawa passive O3 samplers were used in a 13-week study (June 1-September 1, 1999)
      involving 11 forested and mountaintop sites in north-central Pennsylvania. Four
      of the sites were collocated with TECO model 49 O3 analyzers. A significant
      correlation (p < 0.0001) was found for 24-hr average weekly O3 concentrations
      between the two methodologies at the four sites with collocated monitors. As
      expected, there were positive relationships between increasing elevation of the
      sites and increasing O3 concentrations. No O3 exposure patterns were found on a
      west-to-east or south-to-north basis; however, the area known for lower O3
      exposures within a smaller subsection of the study area showed consistently lower
      O3 exposures. Preliminary results regarding relationships of symptom responses
      within O3-sensitive bioindicators are also presented with black cherry (Prunus
      serotina, Ehrh.) and common milkweed (Asclepias syriaca, L.) showing clear
      evidence of increasing injury with increasing O3 exposures. Due to the extremely
      dry conditions encountered in north-central Pennsylvania during the 1999 growing
      season, O3-induced symptoms were sporadic and quite delayed until late-season
      rains during the latter portion of the observation period.

PMID- 11575882
TI  - Deposition of Mn from automotive combustion of methylcyclopentadienyl manganese
      tricarbonyl beside the major highways in the greater Toronto area, Canada.
AB  - Methylcyclopentadienyl manganese tricarbonyl (MMT) has been used in Canada since
      1976 as an antiknock agent in gasoline, completely replacing Pb in 1990. An early
      study of much higher Mn concentrations in gasoline showed that the combustion of
      MMT leads to the formation of inorganic manganese oxides, especially Mn3O4.
      Recent emission testing by Lawrence Livermore National Laboratory for Ethyl Corp.
      has shown that Mn is primarily emitted as a phosphate or sulfate along with minor
      amounts of oxides. The main objective of this research was to analyze the
      deposition of Mn from MMT to the terrestrial environment beside the major
      highways in the greater Toronto area (GTA), Canada. The results were compared
      with Pb and other trace elements such as Al, Ca, Fe, Mg, Cu, Zn, Na, and the Cl
      ion (water extractable) to study the behavior of Mn in soil. The study area was
      located near major Toronto highways 401 (urban) and 400 (rural), at 43 degrees
      67' N and 79 degrees 37' W (latitude and longitude) (278,560 and 47,835
      cars/day), respectively. Surface soil samples (0-5 cm depth) were collected at
      distances up to 40 m from the roadside. Parameters evaluated included total and
      available Mn and other trace elements, particle size, pH, organic content, and
      cation exchange capacity. Based on high traffic density along 401, higher Mn
      deposition was expected. No significant differences were found between the 401
      and 400 Barrie (E(+1)) sites, attributable to the natural background levels of Mn
      or its contribution by other sources such as Mn-enriched road dust or naturally
      occurring crustal Mn. However, the 400 King City (E(+2)) site had significantly
      lower Mn levels than did the other three sites, 401 and 400 Barrie. This may be
      explained by the types of soil along the 401 and 400 sites. The King City site
      along 400 was found to be higher in sand content than were the 401 sites. A
      higher sand content could result in higher leaching of Mn to the bottom layer of
      the soil. Although MMT has been used continuously for approximately 25 years in
      Canada, its contribution to the terrestrial environment has been very low and has
      not significantly increased Mn levels along the highways, as demonstrated by this
      study.

PMID- 11575883
TI  - Determination of fine particulate semi-volatile organic material at three eastern
      U.S. sampling sites.
AB  - Correct assessment of fine particulate carbonaceous material as a function of
      particle size is, in part, dependent on the determination of semi-volatile
      compounds, which can be lost from particles during sampling. This study gives
      results obtained for the collection of fine particulate carbonaceous material at
      three eastern U.S. sampling sites [Philadelphia, PA; Shenandoah National Park,
      VA; and Research Triangle Park (RTP), NC] using diffusion denuder technology. The
      diffusion denuder samplers allow for the determination of fine particulate
      organic material with no artifacts, due to the loss of semi-volatile organic
      particulate compounds, or collection of gas-phase organic compounds by the quartz
      filter during sampling. The results show that an average of 41, 43, and 59% of
      fine particulate organic material was lost as volatilized semi-volatile organic
      material during collection of particles on a filter at Philadelphia, RTP, and
      Shenandoah, respectively. The particle size distribution of carbonaceous material
      retained by a filter and lost from a filter during sampling was obtained for the
      samples collected at Philadelphia and Shenandoah. The carbonaceous material
      retained by the particles during sampling was found predominantly in particles
      smaller than 0.4 microm in aerodynamic diameter. In contrast, the semi-volatile
      organic material lost from the particles during sampling had a mass median
      diameter of approximately 0.5 microm.

PMID- 11575884
TI  - Development and evaluation of a continuous coarse (PM10-PM2.5) particle monitor.
AB  - In this paper, we describe the development and laboratory and field evaluation of
      a continuous coarse (2.5-10 microm) particle mass (PM) monitor that can provide
      reliable measurements of the coarse mass (CM) concentrations in time intervals as
      short as 5-10 min. The operating principle of the monitor is based on enriching
      CM concentrations by a factor of approximately 25 by means of a 2.5-microm cut
      point round nozzle virtual impactor while maintaining fine mass (FM)--that is,
      the mass of PM2.5 at ambient concentrations. The aerosol mixture is subsequently
      drawn through a standard tapered element oscillating microbalance (TEOM), the
      response of which is dominated by the contributions of the CM, due to
      concentration enrichment. Findings from the field study ascertain that a TEOM
      coupled with a PM10 inlet followed by a 2.5-microm cut point round nozzle virtual
      impactor can be used successfully for continuous CM concentration measurements.
      The average concentration-enriched CM concentrations measured by the TEOM were 26
      27 times higher than those measured by the time-integrated PM10 samplers [the
      micro-orifice uniform deposit impactor (MOUDI) and the Partisol] and were highly
      correlated. CM concentrations measured by the concentration-enriched TEOM were
      independent of the ambient FM-to-CM concentration ratio, due to the decrease in
      ambient coarse particle mass median diameter with an increasing FM-to-CM
      concentration ratio. Finally, our results illustrate one of the main problems
      associated with the use of real impactors to sample particles at relative
      humidity (RH) values less than 40%. While PM10 concentrations obtained by means
      of the MOUDI and Partisol were in excellent agreement, CM concentrations measured
      by the MOUDI were low by 20%, and FM concentrations were high by a factor of 5,
      together suggesting particle bounce at low RH.

PMID- 11575885
TI  - The use of indoor air measurements to evaluate intrusion of subsurface VOC vapors
      into buildings.
AB  - The implementation of a risk-based corrective action approach often requires
      consideration of soil vapor migration into buildings and potential inhalation
      exposure and risk to human health. Due to the uncertainty associated with models
      for this pathway, there may be a desire to analyze indoor air samples to validate
      model predictions, and this approach is followed on a somewhat frequent basis at
      sites where risks are considered potentially significant. Indoor air testing can
      be problematic for a number of reasons. Soil vapor intrusion into buildings is
      complex, highly dependent on site-specific conditions, and may vary over time,
      complicating the interpretation of indoor air measurements when the goal is to
      deduce the subsurface-derived component. An extensive survey of indoor air
      quality data sets highlights the variability in indoor volatile organic compound
      (VOC) concentrations and numerous sources that can lead to elevated VOC levels.
      The contribution from soil vapor is likely to be small relative to VOCs from
      other sources for most sites. In light of these challenges, we discuss how
      studies that use indoor air testing to assess subsurface risks could be improved.
      To provide added perspective, we conclude by comparing indoor air concentrations
      and risks arising from subsurface VOCs, predicted using standard model equations
      for soil vapor fate and intrusion into buildings, to those associated with indoor
      sources.

PMID- 11575886
TI  - The nonlinearity and related band strength of carbon monoxide when applied in
      ambient air measurement using open long-path Fourier transform infrared
      spectrometry.
AB  - The accuracy of CO concentration determination by open-path Fourier transform
      infrared (FTIR) spectrometry has been re-evaluated in detail. The evaluation
      focuses on the correction of the calibration curve--the integrated intensity of a
      standard spectrum--that is used as a comparison spectrum when doing quantitative
      analysis of CO. Results show that the calibration curve (with 0.5 cm(-1) or 1 cm(
      1) resolution) is apparently inclined to be nonlinear under standard conditions,
      and that the threshold point of nonlinearity is approximately 0.1 atm-cm. Two
      commercial FTIR field monitoring systems have been used to investigate the
      nonlinearity trend. The experimental method consists of using open-path FTIR
      systems in combination with nondispersive infrared (NDIR) monitors to establish
      the calibration curve in a semi-closed corridor The results have been double
      checked using closed-cell dynamic equilibrium systems. When the optical density
      is larger than a certain value, the curves begin to bend, and when the optical
      density approaches zero, the band strength is around 178 +/- 3 atm(-1) cm(-2) and
      173 +/- 2 atm(-1) cm(-2), respectively, for 0.5 and 1 cm(-1) resolution at
      standard temperature and pressure (STP). These values are quite different from
      other published data that have been acquired by the pressurized method or by high
      resolution (<0.006 cm(-1)) spectrometers. It is thought that a higher accuracy is
      achieved when these new calibration results are used to quantify the CO
      concentration. The error in concentration determination within 0.1 optical
      density is less than 2%, and that in the higher optical density region is less
      than 5%.

PMID- 11575887
TI  - Regional variations in sulfate and nitrate on annual, seasonal, and synoptic time
      scales.
AB  - Ambient data from Interagency Monitoring of Protected Visual Environments
      (IMPROVE) monitors are analyzed to evaluate the spatial structure of SO4 and NO3
      aerosols in the mid-Atlantic region. Sub-weekly, seasonal, and annual data values
      are compared between the IMPROVE Washington, DC, site and three rural sites.
      Synoptic perturbations are compared between sites to quantify similarities in
      short-term temporal perturbations of SO4 and NO3. Based on these comparisons
      between the rural and urban IMPROVE monitors, the spatial structure of SO4 shows
      broad regional homogeneity that is recognizable from both the long-term average
      values and the short-term variations. NO3 data on a seasonal and annual basis
      show much larger spatial gradients between the urban Washington monitor and the
      three rural monitors than do SO4 data. Short-term NO3 perturbations at the three
      rural monitors also differ significantly from those at the Washington site. These
      dissimilarities in NO3 levels between the rural and urban IMPROVE monitors on
      both short-term and longer-term time scales indicate little homogeneity of NO3
      aerosols in the mid-Atlantic region considered here. The volatility of NO3
      aerosols and the removal rate of HNO3 via dry deposition could contribute to the
      spatial variability differences shown here between SO4 and NO3.

PMID- 11575888
TI  - Multivariate space analysis of the major precipitation ions over Europe, 1986
      1997.
AB  - The annual average concentrations (1986-1997) of the major ions SO4(2-), NO3-, Cl
      , NH4+, Na+, Mg2+, Ca2+, and K+ in precipitation are analyzed for selected EMEP
      stations. The objective is to determine the ion patterns or typologies in
      precipitation by principal component analysis (PCA) combined with a cluster
      analysis. SO4(2-) and NO3- ions are predominant in central and eastern Europe.
      This area corresponds to high emissions of SO2 and NO2. Sea spray ions are
      predominant in coastal sites. The soil components show an important contribution
      in southern Europe, possibly due to the soil dust transported from northern
      Africa.

PMID- 11575889
TI  - Removal of hydrocarbons from wastewater using treated bark.
AB  - This paper explores the possibility of removing hydrocarbons (HCs) and trace
      elements from synthetic and industrial effluents using treated bark as
      biosorbent. Coniferous bark was treated either chemically (Tc) or biologically
      (Tb) to eliminate soluble organic compounds of bark. The removal efficiency (RE)
      of the HCs from a synthetic oil-water mixture containing spent diesel motor oil
      exceeds 95% using 2 g/L of treated bark mixed with a synthetic oil-water mixture
      containing 2 g/L of spent oil. Under these conditions, the retention capacity
      (RC) was approximately 1 g HC/g dry substrate. The sorption reaction seems to be
      quasi-instantaneous, and the retention capacity of spent oil on treated bark
      increases as the temperature augments. This implies that the retention mechanism
      is related to the capillary action. Results of Fourier transform infrared (FTIR)
      spectroscopy indicate that spent oil is mainly composed of alkanes. They also
      suggest that no chemical bonds between Tc and spent oil were established.
      Measurement of the surface tension of spent oil and the wetting index of the bark
      suggests that only spent oil will be retained by the substrate. Treatment of an
      industrial effluent containing 14.4 g/L of total HCs was performed using Tc. It
      was possible to remove 97% of HCs and retain some trace elements such as Al, Ca,
      Fe, Mg, S, and so on.

PMID- 11575890
TI  - Aldehyde and monocyclic aromatic hydrocarbon mixing ratios at an urban site in
      Las Vegas, Nevada.
AB  - Oxidation of benzene, toluene, ethylbenzene, and xylenes (BTEX) in air, of
      significance due to, for example, the potential for O3 formation, is believed to
      be initiated by OH attack on the ring (addition) or on the alkyl side chain (H
      abstraction). A series of ring-breaking reactions follows, with major products
      predicted to be alpha-dicarbonyls, simple aldehydes, and organic acids. To test
      this prediction, ambient air mixing ratios of aldehydes (formaldehyde,
      acetaldehyde, benzaldehyde, glyoxal, and pyruvaldehyde), along with some
      supporting BTEX data, were measured at an urban site in Las Vegas, NV. Samples
      were collected on sorbents and determined by chromatographic methods; mixing
      ratios were compared to ambient levels of CO, O3, and NOx. A meteorological
      analysis (temperature, wind speed, and wind direction) was also included.
      Statistically significant relationships were noted among the BTEX hydrocarbons
      (HCs) and among the photochemically derived species (e.g., O3, NO2, and some of
      the aldehydes), although there was seasonal variation. The observations are
      consistent with a common primary source (i.e., vehicular exhaust or fuel
      evaporation) for the BTEX compounds and a common secondary source (e.g., OH
      attack) for glyoxal and pyruvaldehyde.

PMID- 11575891
TI  - History and future perspectives of treating asthma as a systemic and small
      airways disease.
AB  - Asthma is an inflammatory disorder in which the small airways of the lung play an
      important role. There is also evidence for the systemic nature of asthma. No
      current method adequately measures small airways function alone. Therefore, a
      combination of functional and clinical parameters should be used to ensure that
      patients with asthma are adequately treated with due consideration of the small
      airways. Previously therapeutic strategies have focused on bronchodilation and
      attenuation of airway inflammation. While early oral therapies had the advantage
      of reaching the small airways and treating the systemic aspect of asthma, they
      were associated with serious side-effects. Inhaled therapies were therefore
      developed to limit these effects. However, inhaled therapies have the
      disadvantage of limited penetration into the peripheral airways and an inability
      to treat the systemic component of asthma. They are also associated with local
      and systemic side-effects. The future for asthma treatment is likely to be a
      systemically administered medication with few side-effects targeting disease
      specific mediators. The leukotriene receptor antagonists and anti-IgE monoclonal
      antibodies are examples of such therapies and the emergence of other new
      strategies is awaited.

PMID- 11575893
TI  - Benzalkonium chloride as a preservative in nasal solutions: re-examining the
      data.
AB  - Recent studies have suggested that benzalkonium chloride (BKC), an antimicrobial
      agent used as a preservative in nasal sprays, lacks deleterious effects on the
      nasal ciliated epithelium. Other data, including recent in vivo findings, suggest
      that BKC may, in fact, produce adverse clinical effects on human nasal tissue,
      including the aggravation of rhinitis medicamentosa. Toxic effects have also been
      reported. In light of the discrepancy between negative results and studies
      suggesting no safety concerns, we consider the possibility of problems in the
      design and methodology of some of the studies and in the interpretation of
      results. Clearly, further research is warranted to clarify the significance of
      conflicting findings. In the meantime, without conclusive data regarding BKC and
      the possibility of harmful effects, the use of nasal formulations without BKC
      might be a reasonable alternative.

PMID- 11575892
TI  - A comparison of the lung deposition of budesonide from Easyhaler, Turbuhaler and
      pMDI plus spacer in asthmatic patients.
AB  - Inhaled corticosteroids in pressurized metered does inhalers (pMDIs) are often
      delivered via a large volume spacer device, but these are bulky and inconvenient.
      Dry powder inhalers (DPIs) provide a highly portable and convenient propellant
      free alternative to pMDIs for asthma maintenance therapy However, each DPI could
      have unique in vivo delivery characteristcs. In order to quantify the total and
      regional lung deposition of budesonide (200 microg) from (a) Easyhaler, (b)
      Turbuhaler and (c) pMDI plus Nebuhaler 750 ml spacer, a three-way randomized
      cross-over study was carried out in 12 mild to moderate asthmatic patients.
      Deposition was quantified by the imaging technique of gamma scintigraphy Optimal
      inhalation techniques were used throughout. Mean (SD) whole lung deposition (%
      metered dose) was similar for Easyhaler [18.5 (7.8) %] and Turbuhaler [21.8 (8.2)
      %], but was significantly higher for pMDI plus Nebuhaler [44.1 (10.0) %, P <
      0.01]. The regional distribution patterns in the lungs were predominantly central
      for all three devices. Nebuhaler reduced oropharyngeal deposition significantly
      compared with the two DPIs. Easyhaler showed comparable deposition to Turbuhaler
      and hence drugs delivered by Easyhaler would be expected to have a similar
      clinical effect to those delivered by Turbuhaler in asthma maintenance therapy.

PMID- 11575894
TI  - Budesonide but not nedocromil sodium reduces exhaled nitric oxide levels in
      asthmatic children.
AB  - Exhaled nitric oxide (ENO) has been proposed as a marker of airway inflammation
      in asthma and could be useful to evaluate the response to anti-inflammatory
      treatment. We investigated the effect of budesonide and nedocromil sodium on ENO
      levels and lung function in asthmatic children. Twenty stable steroid-naive
      asthmatic children were randomized in a single blind, cross-over study to receive
      inhaled budesonide (group A) or nedocromil sodium (group B) for 6 weeks. ENO was
      measured with a chemiluminescence analyser at baseline and at the end of each
      treatment period. Repeated-measures ANOVA was carried out. In asthmatic baseline
      ENO levels [mean 32.5 ppb, 95% confidence interval (CI) 26.4 to 38.7] were
      significantly higher compared to reference values (8.7 ppb, 95% CI 8.1 to 9.2,
      P<0.001). There were no treatment-order effect, no carry-over effect and in both
      groups the response pattern was the same: budesonide significantly lowered ENO
      levels from 41.0 ppb to 22.8 ppb in group A (mean, P<0.01) and from 22.6 ppb to
      13.0 ppb in group B, (mean, P<0.05), while nedocromil did not reduce ENO values
      (from 24.4 ppb to 22.6 ppb in group B and from 22.8 ppb to 38.0 ppb in group A,
      mean, P = NS and P<0.01 respectively). After budesonide treatment ENO values of
      asthmatics were still significantly higher than in healthy children The baseline
      values of FEV1 and FEF(25-75) were normal in both groups and no significant
      changes were observed during the study. In conclusion, our study shows that
      budesonide, but not nedocromil sodium, significantly reduces ENO levels in stable
      asthmatic children even in absence of changes in the lung function.

PMID- 11575895
TI  - Long-acting bronchodilators in premenstrual exacerbation of asthma.
AB  - Premenstrual exacerbation (PME) of asthma occurs during the 5-10 days leading up
      to the menses and can be demonstrated in about 40% of asthmatic females. Peak
      expiratory flow rate (PEFR) and beta2-agonist consumption were recorded during
      three menstrual cycles in 67 females with mild-severe asthma. All were treated
      with inhaled glucocorticosteroids (IGC) and beta2-agonists, as required.
      Following, the patients with a premenstrual reduction in PEFR > 20%, received
      either salmeterol, 50 microg x 2 day(-1) or placebo, in the 10 days leading up to
      the menses, in a randomized, double-blind, cross-over design. Thirteen patients
      (19.4%) showed PME (mean +/- SEM decrease in PEFR 27 +/- 2.2%) in association
      with a significant increase in the mean daily beta2-agonist consumption.
      Following administration of salmeterol, there was a complete ablation of the PME
      in seven patients, a partial ablation in two patients and no effect in the
      remaining four patients. Only one patient showed a partial ablation of the PME
      following placebo. There was also a significant decrease in the beta2-agonists
      consumption in the responders. About 20% of the women with asthma, under chronic
      IGC treatment, had PME of asthma. In 54% of them, it could be prevented by the
      use of long-acting bronchodilators (LABD) during the 10 days leading up to the
      menses, and partially prevented in another 15%.

PMID- 11575896
TI  - Prevalence of obstructive lung diseases and respiratory symptoms in relation to
      living environment and socio-economic group.
AB  - We wanted to test whether living environment, occupation and social position are
      risk factors for asthma and chronic bronchitis/emphysema (CBE). The prevalence of
      bronchial asthma, CBE, respiratory symptoms and smoking habits in a random sample
      of 12,071 adults aged 20-59 years was assessed in a postal survey with a slightly
      modified questionnaire previously used in central and northern Sweden (The OLIN
      studies). Occupation was coded according to a socio-economic classification
      system. Six different living environment areas were defined; city-countryside,
      seaside-not seaside and living close to heavy traffic-not living close to heavy
      traffic. Multiple logistic regression analysis (forward conditional) was applied
      to estimate the association between the proposed set of risk factors and self
      reported obstructive lung diseases and lower respiratory symptoms controlling for
      age, gender and smoking. After two reminders, the response rate was 70.1%
      (n=8469); 33.8% of the responders were smokers. In all, 469 subjects (5.5%)
      stated that they had asthma and 4.6% reported CBE. Besides smoking, which was a
      risk for both asthma and CBE, there were different risk patterns for self
      reported asthma and CBE. In the economically active population there was a
      tendency that CBE was more common among 'unskilled and semi-skilled workers'.
      This fact was further emphasized when the population was merged into the two
      groups 'low social position' and 'middle/high social position', with 'low social
      position' as a risk for CBE (OR=1.35, 95% CI=1.06-1.72). No social risk factors
      were identified for asthma. Living close to heavy traffic was a risk factor for
      asthma (OR=1.29, 95% CI=1.02-1.62) but not for CBE. Apart from this no living
      environmental risk factors for obstructive pulmonary diseases were identified.
      Asthma symptoms and long-standing cough were more common among those subjects
      living close to heavy traffic compared to those not living close to heavy
      traffic. To conclude, low social position was a risk factor for CBE and living
      close to heavy traffic was a risk factor for asthma.

PMID- 11575897
TI  - A cost-effectiveness study comparing the as-needed use of formoterol (Oxis) and
      terbutaline (Bricanyl) in patients with moderate to severe asthma.
AB  - This study evaluated the economic and health-related consequences of the as
      needed use of a long-acting beta2-agonist with fast onset (formoterol, Oxis
      Turbuhaler 4.5 microg) versus a short-acting beta2-agonist (terbutaline, Bricanyl
      Turbuhaler 0.5 mg) in patients with moderate to severe asthma. A multi-national
      (Sweden, Norway, The Netherlands and Greece), multi-centre (35 centres),
      randomized, double-blind clinical trial was conducted using 362 patients on
      inhaled steroids during a 12-week period. The effectiveness results were pooled
      and the total costs included estimates for beta2-agonists, inhaled steroids, oral
      steroids, physician visits and sick-leave. The 182 patients in the formoterol
      group had 14,404 days of exposure and 29 severe exacerbations, and the 180
      patients in the terbutaline group had 13,655 days of exposure and 48 severe
      exacerbations. The terbutaline group had 62% more severe exacerbations than the
      formoterol group (P=0.039), based on exposure time. Per patient, the calculated
      total costs were SEK 3386 for the formoterol group and SEK 3709 for the
      terbutaline group over the 12-week period. The conclusion is that the use of Oxis
      Turbuhaler instead of Bricanyl Turbuhaler for as-needed treatment is a more
      effective treatment generating cost savings from a societal perspective.

PMID- 11575898
TI  - Screening of obstructive sleep apnoea: heart rate spectral analysis of nocturnal
      pulse oximetric recording.
AB  - Using heart rate spectral analysis of nocturnal pulse oximetry, we prospectively
      evaluated the utility of this methodology in patients clinically suspected of
      having obstructive sleep apnoea (OSA). A hundred and ninety-seven outpatients
      referred with symptoms compatible with the diagnosis of OSA were studied. All
      participants had nocturnal pulse oximetry performed simultaneously with
      conventional polysomnography. Power density of heart rate obtained by nocturnal
      pulse oximetry was analysed using fast Fourier transformation of a Hamming
      windowed signal. Recording test results were classified as abnormal (suspicion of
      OSA) in the presence of a peak in the periodogram between period boundaries 30-70
      sec. A normal test result was defined as the absence of the 30-70 sec peak in the
      periodogram. The total area of the periodogram (S(TOT)), the area enclosed in the
      periodogram between the period boundaries 30-70 sec (S(30-70)), the area enclosed
      in the period boundaries 30-70 sec with respect to the total area of the
      periodogram (S) and the peak amplitude 30-70 sec (PA) were measured. The presence
      of a peak in the periodogram has a sensitivity of 81.3%, a specificity of 91.5% a
      positive predictive value of 89.1% and a negative predictive value of 85.1% for
      OSA diagnosis. The OSA patients were found to have higher values of S(TOT), S(30
      70), S and PA than the non OSA patients. Receiver operating characteristics (ROC)
      curve was constructed at different thresholds of S(TOT), S(30-70) S and PA. For a
      PA threshold of 10(%)2, heart rate spectra analysis sensitivity for OSA was 58%
      and specificity was 92%. Furthermore, the positive and negative predictive values
      for diagnosis of OSA were 87 and 72% respectively. Apnoea hypopnea index (AHI)
      correlated significantly with S(TOT) (r=0.44; P<0.001), S(30-70) (r=0.59:
      P<0.001), S (r=0.58; P<0.001) and PA (r=0.58; P<0.001). According to our results,
      heart rate spectral analys s obtained by nocturnal pulse oximetry and
      identification of peak in the periodogram between period boundaries 30-70 sec
      could be useful as a diagnostic technique for OSA patients.

PMID- 11575899
TI  - Pneumonia as the sole presentation of brucellosis.

PMID- 11575900
TI  - Re: Capsaicin cough sensitivity is decreased in smokers. (Respir. Med. 2001;
      95:19-21).

PMID- 11575901
TI  - Disfluency rates in conversation: effects of age, relationship, topic, role, and
      gender.
AB  - After reviewing situational and demographic factors that have been argued to
      affect speakers' disfluency rates, we examined disfluency rates in a corpus of
      task-oriented conversations (Schober & Carstensen, 2001 ) with variables that
      might affect fluency rates. These factors included: speakers' ages (young, middle
      aged, and older), task roles (director vs. matcher in a referential communication
      task), difficulty of topic domain (abstract geometric figures vs. photographs of
      children), relationships between speakers (married vs. strangers), and gender
      (each pair consisted of a man and a woman). Older speakers produced only slightly
      higher disfluency rates than young and middle-aged speakers. Overall, disfluency
      rates were higher both when speakers acted as directors and when they discussed
      abstract figures, confirming that disfluencies are associated with an increase in
      planning difficulty. However, fillers (such as uh) were distributed somewhat
      differently than repeats or restarts, supporting the idea that fillers may be a
      resource for or a consequence of interpersonal coordination.

PMID- 11575902
TI  - Perceiving non-native speech.
AB  - In a series of experiments using monosyllabic words produced by a native and a
      non-native speaker of English, native English speakers monitored the word-initial
      consonants of the words to decide which of two consonants was present on each
      trial. In some of the experiments, a secondary task of a linguistic nature,
      deciding whether the target-bearing word was a noun or verb, was also required.
      When the words were presented in silence, the native and non-native stimuli were
      processed in a like manner. Specifically, when the secondary task was not
      required, phonemic decisions tended to be made on the basis of prelexical
      information, whereas when the secondary task was required, they tended to be made
      on the basis of postlexical information (see Eimas, Marcovitz Hornstein, &
      Payton, 1990). However, when the listening conditions were degraded by presenting
      the words at a lower level and in noise, the two types of stimuli yielded
      different patterns. Native speech was processed as before, whereas for non-native
      speech phonemic decisions now tended to be made on the basis of postlexical
      information both when a secondary task was required and when it was not. The
      contrasting results for native and non-native speech are discussed in terms of
      models of phoneme processing.

PMID- 11575903
TI  - Voornaam is not (really) a homophone: Lexical prosody and lexical access in
      Dutch.
AB  - Four experiments examined Dutch listeners' use of suprasegmental information in
      spoken-word recognition. Isolated syllables excised from minimal stress pairs
      such as VOORnaam/voorNAAM could be reliably assigned to their source words. In
      lexical decision, no priming was observed from one member of minimal stress pairs
      to the other, suggesting that the pairs' segmental ambiguity was removed by
      suprasegmental information. Words embedded in nonsense strings were harder to
      detect if the nonsense string itself formed the beginning of a competing word,
      but a suprasegmental mismatch to the competing word significantly reduced this
      inhibition. The same nonsense strings facilitated recognition of the longer words
      of which they constituted the beginning, but again the facilitation was
      significantly reduced by suprasegmental mismatch. Together these results indicate
      that Dutch listeners effectively exploit suprasegmental cues in recognizing
      spoken words. Nonetheless, suprasegmental mismatch appears to be somewhat less
      effective in constraining activation than segmental mismatch.

PMID- 11575904
TI  - Rate-induced resyllabification revisited.
AB  - This paper presents the results of a rate scaling speech production experiment
      which seeks to replicate and examine in greater detail the results of a set of
      experiments reported in Stetson (1951). Stetson observed, based on a set of
      pioneering articulatory experiments, that coda consonants resyllabify as onset
      consonants in syllables repeated at fast speech rates. In the current experiment,
      speakers produced repetitions of simple CV and VC syllables in time to a
      metronome pacer which systematically changed in period. Data indicate that, while
      durational patterns for CV and VC syllables are very different at slow rates, the
      patterns tend to converge at fast rates. However, closer examination of fast rate
      tokens, reveals that differences between CV and VC tokens persist at fast rates,
      even though such tokens are generally heard as CV tokens. These results are
      discussed with respect to the nature of CV and VC organization and the effect of
      the rate-changing task.

PMID- 11575905
TI  - A direct assessment of the relation between shared knowledge and communication in
      a referential communication task.
AB  - The present paper introduces a way to document quantitatively the changing
      relation between shared knowledge and communication over time. It is often
      assumed that people engaged in prolonged interaction come to share more knowledge
      over the course of interaction, and, further, it is assumed that this increase in
      shared knowledge enables them to communicate more efficiently with each other. In
      Experiments 1 and 2, this assumption was evaluated by monitoring the
      participants' knowledge of the experimental stimuli and their estimates about
      each other's knowledge periodically during several trials of a referential
      communication task. The results confirmed that participants developed more shared
      knowledge over the course of interaction, and that their estimates about shared
      knowledge become more accurate over successive trials. Experiment 3 was conducted
      in order to examine whether the use of intervening questionnaires in the earlier
      experiments prompted the participants to behave differently than they otherwise
      would. Although the use of the questionnaires encouraged a more active exchange
      of information, the overall pattern of behavior exhibited by the participants was
      not affected by this procedure.

PMID- 11575906
TI  - Can we make a difference?

PMID- 11575907
TI  - Bioabsorbable implants in orthopaedics: new developments and clinical
      applications.
AB  - The use of bioabsorbable implants in orthopaedic surgical procedures is becoming
      more frequent. Advances in polymer science have allowed the production of
      implants with the mechanical strength necessary for such procedures.
      Bioabsorbable materials have been utilized for the fixation of fractures as well
      as for soft-tissue fixation. These implants offer the advantages of gradual load
      transfer to the healing tissue, reduced need for hardware removal, and
      radiolucency, which facilitates postoperative radiographic evaluation. Reported
      complications with the use of these materials include sterile sinus tract
      formation, osteolysis, synovitis, and hypertrophic fibrous encapsulation. Further
      study is required to determine the clinical situations in which these materials
      are of most benefit.

PMID- 11575908
TI  - Orthopaedics in the developing world: present and future concerns.
AB  - Half of the world's population lack access to adequate primary health care, and
      two thirds lack access to orthopaedic care. Globally, the need for health care
      outstrips the available resources. This problem is compounded in the developing
      world by a lack of trained medical personnel, a lack of medical facilities, and,
      in many regions, an inability to access existing facilities. There is little
      specific epidemiologic data about the exact burden of musculoskeletal disease in
      these countries, but most agree that it is reasonable to assume that it will
      increase. In the least developed and developing nations, problems with access are
      related to fundamental issues such as infrastructure, physical facilities,
      equipment, and trained personnel. There are a number of ways in which the
      orthopaedic community can become involved in ameliorating the burden. Education
      is the most effective method of providing a sustainable solution. The objective
      of educational organizations should be to train local health-care workers at all
      levels in their own environment to provide sustainable and appropriate care so
      that the programs become self-sufficient and ensure a continued supply of
      competent medical personnel.

PMID- 11575909
TI  - Posterior cruciate ligament injuries: evaluation and management.
AB  - Posterior cruciate ligament (PCL) injuries commonly occur during sports
      participation or as a result of motor vehicle accidents. Careful history taking
      and a comprehensive physical examination are generally sufficient to identify PCL
      injuries. Most authors recommend nonoperative treatment for acute isolated PCL
      tears. This involves initial splinting in extension followed by range-of-motion
      and strengthening exercises. Recovery of quadriceps strength is necessary to
      compensate for posterior tibial subluxation and to facilitate return to preinjury
      activity levels. In isolated PCL tears, surgical treatment is reserved for acute
      bone avulsions and symptomatic chronic high-grade PCL tears. Arthroscopic single
      tunnel reconstruction techniques will improve posterior laxity only moderately.
      Newer double-tunnel and tibial-inlay techniques offer theoretical advantages, but
      the available clinical results are only preliminary. When a PCL injury occurs in
      combination with other ligament injuries, most patients will require surgical
      treatment.

PMID- 11575910
TI  - Pediatric foot fractures: evaluation and treatment.
AB  - Foot fractures account for 5% to 8% of all pediatric fractures and for
      approximately 7% of all physeal fractures. A thorough understanding of the
      anatomy of the child's foot is of central importance when treating these
      injuries. Due to the difficulties that may be encountered in obtaining an
      accurate physical examination of a child with a foot injury and the complexities
      of radiographic evaluation of the immature foot, a high index of suspicion for
      the presence of a fracture facilitates early and accurate diagnosis. Although the
      treatment results in pediatric foot trauma are generally good, potential pitfalls
      in the treatment of Lisfranc fractures, talar neck and body fractures, and lawn
      mower injuries to the foot must be anticipated and avoided if possible.

PMID- 11575911
TI  - Primary osteoarthritis of the hip: etiology and epidemiology.
AB  - Primary osteoarthritis (OA) of the hip has a distinct etiology and epidemiology
      compared with other types of arthropathy in the hip joint. Arthritis of the hip
      can be secondary to conditions such as osteonecrosis, trauma, sepsis, or
      rheumatoid arthritis. Certain conditions, such as congenital hip disease and
      slipped capital femoral epiphysis, involve predisposing anatomic abnormalities;
      in such cases, the term "secondary OA" is used. When either an anatomic
      abnormality cannot be determined or other specific causative entities are not
      identified, primary OA is the diagnosis of exclusion. The prevalence of hip OA is
      about 3% to 6% in the Caucasian population and has not changed in the past four
      decades. In contrast, studies in Asian, black, and East Indian populations
      indicate a very low prevalence of hip OA. Statistics on patients who underwent
      total hip replacement for primary OA in San Francisco and Hawaii demonstrate a
      virtual absence of the condition in Asians and low rates in the black and
      Hispanic populations. Family studies from Sweden, Britain, and the United States
      show increased rates of hip OA in first-degree relatives of the index patient
      when compared with the normal population. Occupations requiring heavy lifting,
      farming, and elite sports activity are associated with increased rates of hip OA.
      The low prevalence of hip OA in Asian and black populations in their native
      countries; the low incidence of total joint replacement for primary OA in Asian,
      black, and Hispanic populations in North America; and the familial association of
      hip OA in Caucasians all suggest that genetic factors may be involved in the
      occurrence of this disease.

PMID- 11575912
TI  - Axillary nerve injury: diagnosis and treatment.
AB  - Axillary nerve injury is infrequently diagnosed but is not a rare occurrence.
      Injury to the nerve may result from a traction force or blunt trauma applied to
      the shoulder. The most common zone of injury is just proximal to the
      quadrilateral space. Atraumatic causes of neuropathy include brachial neuritis
      and quadrilateral space syndrome. The vast majority of patients recover with non
      operative treatment. Baseline electromyographic and nerve conduction studies
      should be obtained within 4 weeks after injury, with a follow-up evaluation at 12
      weeks. If no clinical or electromyographic improvement is noted, surgery may be
      appropriate. The results of operative repair are best if surgery is performed
      within 3 to 6 months from the injury. Surgical options include neurolysis, nerve
      grafting, and neurotization. The results of repair of axillary nerve injuries
      have been good compared with treatment of other peripheral nerve lesions, due to
      the monofascicular composition of the nerve and the relatively short distance
      between the zone of injury and the motor end-plate.

PMID- 11575913
TI  - Meralgia paresthetica: diagnosis and treatment.
AB  - Meralgia paresthetica is a symptom complex that includes numbness, paresthesias,
      and pain in the anterolateral thigh, which may result from either an entrapment
      neuropathy or a neuroma of the lateral femoral cutaneous nerve (LFCN). The
      condition can be differentiated from other neurologic disorders by the typical
      exacerbating factors and the characteristic distribution of symptoms. The disease
      process can be either spontaneous or iatrogenic. The spontaneous form is usually
      mechanical in origin. The LFCN is subject to compression throughout its entire
      course. Injuries most commonly occur as the nerve exits the pelvis. The regional
      anatomy of the LFCN is highly varied and may account for its susceptibility to
      local trauma. Relief of pain and paresthesias after injection of a local
      anesthetic agent is helpful in establishing the diagnosis. If no improvement is
      found, proximal LFCN irritation should be sought. Idiopathic meralgia
      paresthetica usually improves with nonoperative modalities, such as removal of
      compressive agents, nonsteroidal anti-inflammatory drugs, and, if necessary,
      local corticosteroid injections. If intractable pain persists despite such
      measures, surgery can be considered, although whether neurolysis or transection
      is the procedure of choice is still controversial. Iatrogenic meralgia
      paresthetica has been found to occur after a number of orthopaedic procedures,
      such as anterior iliac-crest bone-graft harvesting and anterior pelvic
      procedures. Prone positioning for spine surgery has also been implicated.
      Variations in the anatomy of the LFCN about the anterior superior iliac spine may
      place the nerve at higher risk for damage. Although nonoperative management
      usually results in satisfactory results, efforts should be made to avoid injury
      at the time of surgery.

PMID- 11575914
TI  - Pneumatic tourniquets in extremity surgery.
AB  - Pneumatic tourniquets maintain a relatively bloodless field during extremity
      surgery, minimize blood loss, aid identification of vital structures, and
      expedite the procedure. However, they may induce an ischemia-reperfusion injury
      with potentially harmful local and systemic consequences. Modern pneumatic
      tourniquets are designed with mechanisms to regulate and maintain pressure.
      Routine maintenance helps ensure that these systems are working properly. The
      complications of tourniquet use include postoperative swelling, delay of recovery
      of muscle power, compression neurapraxia, wound hematoma with the potential for
      infection, vascular injury, tissue necrosis, and compartment syndrome. Systemic
      complications can also occur. The incidence of complications can be minimized by
      use of wider tourniquets, careful preoperative patient evaluation, and adherence
      to accepted principles of tourniquet use.

PMID- 11575915
TI  - Promoter-specific involvement of the FixJ receiver domain in transcriptional
      activation.
AB  - The "two-component" FixLJ system activates nitrogen fixation genes via nifA and
      fixK in Sinorhizobium meliloti. Like other response regulators, the FixJ protein
      can be decomposed into an N-terminal phosphorylatable "receiver" domain FixJN and
      a C-terminal transcriptional activator domain FixJC. The FixJN receiver domain
      was known to regulate activity of FixJC negatively at the nifA promoter. Here we
      show a different situation at the fixK promoter where FixJN also contributes
      positively to transcriptional activation. This promoter-specific effect was
      mapped by alanine-scanning mutagenesis to the beta2 strand of the receiver
      domain. This interaction with FixJN is required for the recruitment of RNA
      polymerase at the fixK promoter by phosphorylated FixJ. Altogether the FixJ
      receiver domain appears to carry at least four functions, some of which can be
      separated by mutation: (1) autophosphorylation; (2) inhibition of FixJC; (3)
      dimerization; (4) transcriptional activation at pfixK. This example illustrates
      the formidable functional plasticity of receiver domains.

PMID- 11575916
TI  - Porous silicon: an effective nucleation-inducing material for protein
      crystallization.
AB  - Protein crystals play a pivotal part in structural genomics, hence there is an
      urgent requirement for new and improved methodology to aid crystal growth.
      Considerable effort has been invested in the search of substances (nucleants)
      that will induce efficient nucleation of protein crystals in a controlled manner.
      To date, nucleation has been facilitated mainly by seeding, epitaxy, charged
      surfaces or mechanical means. A different approach is introduced here, involving
      the use of a mesoporous material that is likely to constrain protein molecules
      and thereby encourage them to aggregate in crystalline order. Large single
      crystals were obtained using porous silicon at conditions that are not sufficient
      for spontaneous nucleation, for five out of six proteins that were investigated.
      We propose that this success is due to the size distribution of pores in the
      specially designed porous silicon.

PMID- 11575917
TI  - Multiple procyclin isoforms are expressed differentially during the development
      of insect forms of Trypanosoma brucei.
AB  - Transmission of Trypanosoma brucei by the tsetse fly entails several rounds of
      differentiation as the parasite migrates through the digestive tract to the
      salivary glands of its vector. Differentiation of the bloodstream to the
      procyclic form in the fly midgut is accompanied by the synthesis of a new coat
      consisting of EP and GPEET procyclins. There are three closely related EP
      isoforms, two of which (EP1 and EP3) contain N-glycans. To identify the
      individual EP isoforms that are expressed early during synchronous
      differentiation in vitro, we exploited the selective extraction of GPI-anchored
      proteins and mass spectrometry. Unexpectedly, we found that GPEET and all
      isoforms of EP were coexpressed for a few hours at the onset of differentiation.
      At this time, the majority of EP1 and EP3 molecules were already glycosylated.
      Within 24 hours, GPEET became the major surface component, to be replaced in turn
      by glycosylated forms of EP, principally EP1, at a later phase of development.
      Transient transfection experiments using reporter genes revealed that each
      procyclin 3' untranslated region contributes to differential expression as the
      procyclic form develops. We postulate that programmed expression of other
      procyclin species will accompany further rounds of differentiation, enabling the
      parasite to progress through the fly.

PMID- 11575918
TI  - The RING domains of the promyelocytic leukemia protein PML and the arenaviral
      protein Z repress translation by directly inhibiting translation initiation
      factor eIF4E.
AB  - The promyelocytic leukemia protein (PML) is a mammalian regulator of cell growth
      which is characteristically disrupted in acute promyelocytic leukemia and by a
      variety of viruses. PML contains a RING domain which is required for its growth
      suppressive and antiviral properties. Although normally nuclear, in certain
      pathogenic conditions, including arenaviral infection, PML is relocated to the
      cytoplasm, where its functions are poorly understood. Here, we observe that PML
      and arenavirus protein Z use regions around the first zinc-binding site of their
      respective RING domains to directly interact, with sub-micromolar affinity, with
      the dorsal surface of translation initiation factor eIF4E, representing a novel
      mode of eIF4E recognition. PML and Z profoundly reduce the affinity of eIF4E for
      its substrate, the 5' 7-methyl guanosine cap of mRNA, by over 100-fold.
      Association with the dorsal surface of eIF4E and direct antagonism of mRNA cap
      binding by PML and Z lead to direct inhibition of translation. These activities
      of the RING domains of PML and Z do not involve ubiquitin-mediated protein
      degradation, in contrast to many RINGs which have been observed to do so.
      Although PML and Z have well characterized physiological functions in regulation
      of growth and apoptosis, this work establishes the first discrete biochemical
      mechanism which underlies the biological activities of their RING domains. Thus,
      we establish PML and Z as translational repressors, with potential contributions
      to the pathogenesis of acute promyelocytic leukemia and variety of viral
      infections.

PMID- 11575919
TI  - Leucine-regulated self-association of leucine-responsive regulatory protein (Lrp)
      from Escherichia coli.
AB  - Lrp is a global regulatory protein in Escherichia coli that activates expression
      of more than a dozen operons and represses expression of another dozen. For some
      operons, exogenous leucine reduces the extent of Lrp action, for others it
      potentiates the effect of Lrp, and for yet other operons it has no effect. In an
      effort to understand how leucine affects Lrp-mediated expression, we examined Lrp
      self-association and the effect of leucine on self-association using light
      scattering, chemical cross-linking, and analytical ultracentrifugation. The
      following results were obtained. (i) Lrp self-associates to a hexadecamer and
      octamer with the predominant species being hexadecamer at microM concentrations.
      (ii) Lrp undergoes a leucine-induced dissociation of hexadecamer to octamer.
      (iii) A mutant Lrp lacking 11 amino acid residues at the C terminus does not form
      higher-order oligomers, suggesting that the C terminus is involved in subunit
      association. (iv) At nM concentrations, Lrp dissociates to a dimer. It is
      proposed that leucine regulates the equilibrium between Lrp oligomers and thus
      Lrp occupancy of sites within different operons, leading to diverse regulatory
      patterns.

PMID- 11575920
TI  - High affinity cooperative DNA binding by the yeast Mlh1-Pms1 heterodimer.
AB  - We demonstrate here that the Saccharomyces cerevisiae Mlh1-Pms1 heterodimer
      required for DNA mismatch repair and other cellular processes is a DNA binding
      protein. Binding was evaluated using a variety of single and double-stranded DNA
      molecules. Mlh1-Pms1 bound short substrates with low affinity and showed a slight
      preference for single-stranded DNA. In contrast, Mlh1-Pms1 exhibited a much
      higher affinity for long DNA molecules, suggesting that binding is cooperative.
      High affinity binding required a duplex DNA length greater than 241 base-pairs.
      The rate of association with DNA was rapid and dissociation of protein-DNA
      complexes following extensive dilution was very slow. However, in competition
      experiments, we observed a rapid active transfer of Mlh1-Pms1 from labeled to
      unlabeled DNA. Binding was non-sequence specific and highly sensitive to salt
      type and concentration, suggesting that Mlh1-Pms1 primarily interacts with the
      DNA backbone via ionic contacts. Cooperative binding was observed visually by
      atomic force microscopy as long, continuous tracts of Mlh1-Pms1 protein bound to
      duplex DNA. These images also showed that Mlh1-Pms1 simultaneously interacts with
      two different regions of duplex DNA. Taken together, the atomic force microscope
      images and DNA binding assays provide strong evidence that Mlh1-Pms1 binds duplex
      DNA with positive cooperativity and that there is more than one DNA binding site
      on the heterodimer. These DNA binding properties of Mlh1-Pms1 may be relevant to
      its participation in DNA mismatch repair, recombination and cellular responses to
      DNA damage.

PMID- 11575921
TI  - SF2/ASF binds to a splicing enhancer in the third HIV-1 tat exon and stimulates
      U2AF binding independently of the RS domain.
AB  - Splicing of a single HIV-1 primary transcript into more than 30 different mRNAs
      is regulated by a combination of suboptimal splice sites, cis-acting RNA splicing
      enhancers and silencers, and trans-acting factors. We have studied the splicing
      of the second tat intron (SD4 to SA7) and find that activation of splicing by
      SF2/ASF is mediated by a degenerate exon splicing enhancer (ESE3), consisting of
      at least three functionally independent sub-elements. One of these sub-elements
      appears to have both enhancing and silencing properties, depending on the
      context. SF2/ASF stimulates U2AF65 binding to the suboptimal tat polypyrimidine
      tract in an ESE3-dependent manner, whereas the exon splicing silencer (ESS3) that
      is located downstream of the ESE3 inhibits this step. Truncated SF2/ASF protein
      without the RS domain binds specifically to the ESE3 and retains almost full
      capacity to stimulate U2AF65 binding and activate splicing. This suggests that
      SF2/ASF can stimulate the recruitment of U2AF65 by an RS domain-independent
      mechanism.

PMID- 11575922
TI  - The A730 loop is an important component of the active site of the VS ribozyme.
AB  - The core of the VS ribozyme comprises five helices, that act either in cis or in
      trans on a stem-loop substrate to catalyse site-specific cleavage. The structure
      of the 2-3-6 helical junction indicates that a cleft is formed between helices II
      and VI that is likely to serve as a receptor for the substrate. Detailed analysis
      of sequence variants suggests that the base bulges of helices II and VI play an
      architectural role. By contrast, the identity of the nucleotides in the A730 loop
      is very important for ribozyme activity. The base of A756 is particularly vital,
      and substitution by any other nucleotide or ablation of the base leads to a major
      reduction in cleavage rate. However, variants of A756 bind substrate efficiently,
      and are not defective in global folding. These results suggest that the A730 loop
      is an important component of the active site of the ribozyme, and that A756 could
      play a key role in catalysis.

PMID- 11575923
TI  - The peptidyl-prolyl isomerase Pin1 interacts with hSpt5 phosphorylated by Cdk9.
AB  - We identify and characterize several phosphorylated forms of the hSpt5 subunit of
      the DRB sensitivity-inducing factor (DSIF). A 175-kDa phosphorylated form of
      hSpt5 is bound to nuclei of interphase HeLa cells. This form is rapidly
      dephosphorylated when cultured cells are exposed to various drugs belonging to
      distinct chemical families. All these compounds are known to inhibit the protein
      kinase Cdk9, which phosphorylates in vitro hSpt5 and Rpb1, the largest subunit of
      RNA polymerase II. The efficiency to promote the dephosphorylation of both
      proteins matches their capacity to inhibit purified Cdk9 kinase, suggesting that
      Cdk9 is the major kinase phosphorylating hSpt5 and Rpb1 in vivo. We show that
      Cdk9 phosphorylates both the CTR1 and the CTR2 domains of recombinant hSpt5.
      These domains contain numerous serine-proline and threonine-proline residues
      similar to those found in the carboxyl-terminal domain (CTD) of Rpb1. The
      structural homology between hSpt5 CTRs and the Rpb1 CTD is further highlighted by
      the presence on both proteins of a phosphoepitope recognized by the monoclonal
      antibody CC-3. Of particular interest, the peptidyl-prolyl isomerase Pin1
      interacts with Cdk9-phosphorylated hSpt5. Cdk9 dependent phosphorylation of Rpb1
      and hSpt5 followed by Pin1 interaction might thus contribute to the regulation of
      transcription, pre-mRNA maturation, and the dynamics of these proteins in
      interphase and mitosis.

PMID- 11575924
TI  - DNA cleavage by type III restriction-modification enzyme EcoP15I is independent
      of spacer distance between two head to head oriented recognition sites.
AB  - The type III restriction-modification enzyme EcoP15I requires the interaction of
      two unmethylated, inversely oriented recognition sites 5'-CAGCAG in head to head
      configuration to allow an efficient DNA cleavage. It has been hypothesized that
      two convergent DNA-translocating enzyme-substrate complexes interact to form the
      active cleavage complex and that translocation is driven by ATP hydrolysis. Using
      a half-automated, fluorescence-based detection method, we investigated how the
      distance between two inversely oriented recognition sites affects DNA cleavage
      efficiency. We determined that EcoP15I cleaves DNA efficiently even for two
      adjacent head to head or tail to tail oriented target sites. Hence, DNA
      translocation appears not to be required for initiating DNA cleavage in these
      cases. Furthermore, we report here that EcoP15I is able to cleave single-site
      substrates. When we analyzed the interaction of EcoP15I with DNA substrates
      containing adjacent target sites in the presence of non-hydrolyzable ATP
      analogues, we found that cleavage depended on the hydrolysis of ATP. Moreover, we
      show that cleavage occurs at only one of the two possible cleavage positions of
      an interacting pair of target sequences. When EcoP15I bound to a DNA substrate
      containing one recognition site in the absence of ATP, we observed a 36
      nucleotide DNaseI-footprint that is asymmetric on both strands. All of our
      footprinting experiments showed that the enzyme did not cover the region around
      the cleavage site. Analyzing a DNA fragment with two head to head oriented
      recognition sites, EcoP15I protected 27-33 nucleotides around the recognition
      sequence, including an additional region of 26 bp between both cleavage sites.
      For all DNA substrates examined, the presence of ATP caused altered footprinting
      patterns. We assume that the altered patterns are most likely due to a
      conformational change of the enzyme. Overall, our data further refine the
      tracking-collision model for type III restriction enzymes.

PMID- 11575925
TI  - Changing the direction of flagellar rotation in bacteria by modulating the ratio
      between the rotational states of the switch protein FliM.
AB  - One of the major questions in bacterial chemotaxis is how the switch, which
      controls the direction of flagellar rotation, functions. It is well established
      that binding of the signaling molecule CheY to the switch protein FliM shifts the
      rotation from the default direction, counterclockwise, to clockwise. How this
      shift is done is still a mystery. Our aim in this study was to determine the
      correlation between the fraction of FliM molecules in the clockwise state (i.e.
      occupied by CheY) and the probability of clockwise rotation. For this purpose we
      gradually expressed, from a plasmid, a clockwise FliM mutant protein in cells
      that express, from the chromosome, wild-type FliM but no chemotaxis proteins. We
      verified that plasmid-borne FliM exchanges chromosomal FliM in the switch.
      Surprisingly, a substantial clockwise probability was not obtained before the
      large majority of the FliM molecules in the switch were clockwise molecules.
      Thereafter, the rise in clockwise probability was very steep. These results
      suggest that an increase in the clockwise probability requires a high level of
      FliM occupancy by CheY approximately P. They further suggest that the steep
      increase in clockwise rotation upon increasing CheY levels, reported in several
      studies, is due, at least in part, to cooperativity of post-binding interactions
      within the switch. We also carried out the inverse experiment, in which wild-type
      FliM was gradually expressed in a background of a clockwise fliM mutant. In this
      case, the level of the clockwise mutant protein, required for establishing a
      certain clockwise probability, was lower than in the original experiment. If our
      system (in which the ratio between the rotational states of FliM in the switch is
      established by slow exchange) and the native system (in which the ratio is
      established by fast changes in FliM occupancy) are comparable, the results
      suggest that hysteresis is involved in the switch function. Such a situation
      might reflect a damping mechanism, which prevents a situation in which
      fluctuations in the phosphorylation level of CheY throw the switch from one
      direction of rotation to the other.

PMID- 11575926
TI  - Molecular dissection of the CD2-CD58 counter-receptor interface identifies CD2
      Tyr86 and CD58 Lys34 residues as the functional "hot spot".
AB  - The heterophilic CD2-CD58 adhesion interface contains interdigitating residues
      that impart high specificity and rapid binding kinetics. To define the hot spot
      of this counter-receptor interaction, we characterized CD2 adhesion domain
      variants harboring a single mutation of the central Tyr86 or of each amino acid
      residue forming a salt link/hydrogen bond. Alanine mutations at D31, D32 and K34
      on the C strand and K43 and R48 on the C' strand reduce affinity for CD58 by 47
      127-fold as measured by isothermal titration calorimetry. The Y86A mutant reduces
      affinity by approximately 1000-fold, whereas Y86F is virtually without effect,
      underscoring the importance of the phenyl ring rather than the hydroxyl moiety.
      The CD2-CD58 crystal structure offers a detailed view of this key functional
      epitope: CD2 D31 and D32 orient the side-chain of CD58 K34 such that CD2 Y86
      makes hydrophobic contact with the extended aliphatic component of CD58 K34
      between CD2 Y86 and CD58 F46. The elucidation of this hot spot provides a new
      target for rational design of immunosuppressive compounds and suggests a general
      approach for other receptors.

PMID- 11575927
TI  - Kinetic mechanism of end-to-end annealing of actin filaments.
AB  - We investigated the effect of actin filament length and capping protein on the
      rate of end-to-end annealing of actin filaments. Long filaments were fragmented
      by shearing and allowed to recover. Stabilizing filaments with phalloidin in most
      experiments eliminated any contribution of subunit dissociation and association
      to the redistribution of lengths but did not affect the results. Two different
      assays, fluorescence microscopy to measure filament lengths and polymerization to
      measure concentration of barbed filament ends, gave the same time-course of
      annealing. The rate of annealing declines with time as the average filament
      length increases. Longer filaments also anneal slower than short filaments. The
      second-order annealing rate constant is inversely proportional to mean polymer
      length with a value of 1.1 mM(-1) s(-1)/length in subunits. Capping protein slows
      but does not prevent annealing. Annealing is a highly favorable reaction with a
      strong influence on the length of polymers produced by spontaneous polymerization
      and should be considered in thinking about polymer dynamics in cells.

PMID- 11575928
TI  - Substrate specificity determinants of human macrophage elastase (MMP-12) based on
      the 1.1 A crystal structure.
AB  - The macrophage elastase enzyme (MMP-12) expressed mainly in alveolar macrophages
      has been identified in the mouse lung as the main destructive agent associated
      with cigarette smoking, which gives rise to emphysema, both directly via elastin
      degradation and indirectly by disturbing the proteinase/antiproteinase balance
      via inactivation of the alpha1-proteinase inhibitor (alpha1-PI), the antagonist
      of the leukocyte elastase. The catalytic domain of human recombinant MMP-12 has
      been crystallized in complex with the broad-specificity inhibitor batimastat (BB
      94). The crystal structure analysis of this complex, determined using X-ray data
      to 1.1 A and refined to an R-value of 0.165, reveals an overall fold similar to
      that of other MMPs. However, the S-shaped double loop connecting strands III and
      IV is fixed closer to the beta-sheet and projects its His172 side-chain further
      into the rather hydrophobic active-site cleft, defining the S3 and the S1-pockets
      and separating them from each other to a larger extent than is observed in other
      MMPs. The S2-site is planar, while the characteristic S1'-subsite is a continuous
      tube rather than a pocket, in which the MMP-12-specific Thr215 replaces a Val
      residue otherwise highly conserved in almost all other MMPs. This alteration
      might allow MMP-12 to accept P1' Arg residues, making it unique among MMPs. The
      active-site cleft of MMP-12 is well equipped to bind and efficiently cleave the
      AlaMetPhe-LeuGluAla sequence in the reactive-site loop of alpha1-PI, as occurs
      experimentally. Similarities in contouring and particularly a common surface
      hydrophobicity both inside and distant from the active-site cleft explain why MMP
      12 shares many substrates with matrilysin (MMP-7). The MMP-12 structure is an
      excellent template for the structure-based design of specific inhibitors for
      emphysema therapy and for the construction of mutants to clarify the role of this
      MMP.

PMID- 11575929
TI  - Crystal structure of human macrophage elastase (MMP-12) in complex with a
      hydroxamic acid inhibitor.
AB  - Human macrophage elastase (MMP-12) is a member of the family of matrix
      metalloproteinases (MMPs) that plays, like other members of the family, an
      important role in inflammatory processes contributing to tissue remodelling and
      destruction. In particular, a prominent role of MMP-12 in the destruction of
      elastin in the lung alveolar wall and the pathogenesis of emphysema has been
      suggested. It is therefore an attractive therapeutic target. We describe here the
      crystal structure of the catalytic domain of MMP-12 in complex with a hydroxamic
      acid inhibitor, CGS27023A. MMP-12 adopts the typical MMP fold and binds a
      structural zinc ion and three calcium ions in addition to the catalytic zinc ion.
      The enzyme structure shows an ordered N terminus close to the active site that is
      identical in conformation with the superactivated form of MMP-8. The S1'
      specificity pocket is large and extends into a channel through the protein, which
      puts MMP-12 into the class of MMPs 3, 8 and 13 with large and open specificity
      pockets. The two crystallographically independent molecules adopt different
      conformations of the S1'-loop and its neighbouring loop due to differing crystal
      packing environments, suggesting that flexibility or the possibility of
      structural adjustments of these loop segments are intrinsic features of the MMP
      12 structure and probably a common feature for all MMPs. The inhibitor binds in a
      bidentate fashion to the catalytic zinc ion. Its polar groups form hydrogen bonds
      in a substrate-like manner with beta-strand sIV of the enzyme, while the
      hydrophobic substituents are either positioned on the protein surface and are
      solvent-exposed or fill the upper part of the specificity pocket. The present
      structure enables us to aid the design of potent and selective inhibitors for MMP
      12.

PMID- 11575930
TI  - Zipper-like Watson-Crick base-pairs.
AB  - A series of DNA heptadecamers containing the DNA analogues of RNA E-like 5'
      d(GXA)/(AYG)-5' motifs (X/Y is complementary T/A, A/T, C/G, or G/C pair) were
      studied using nuclear magnetic resonance (NMR) methodology and distance geometry
      (DG)/molecular dynamics (MD) approaches. Such oligomers reveal excellent
      resolution in NMR spectra and exhibit many unusual nuclear Overhauser effects
      (NOEs) that allow for good characterization of an unusual zipper-like
      conformation with zipper-like Watson-Crick base-pairs; the potential canonical
      X.Y H-bonding is not present, and the central X/Y pairs are transformed instead
      into inter-strand stacks that are bracketed by sheared G.A base-pairs. Such
      phenomenal structural change is brought about mainly through two backbone
      torsional angle adjustments, i.e. delta from C2'-endo to C3'-endo for the sugar
      puckers of unpaired residues and gamma from gauche(+) to trans for the following
      3'-adenosine residues. Such motifs are analogous to the previously studied
      (GGA)(2) motif presumably present in the human centromeric (TGGAA)(n) tandem
      repeat sequence. The novel zipper-like motifs are only 4-7 deg. C less stable
      than the (GGA)(2) motif, suggesting that inter-strand base stacking plays an
      important role in stabilizing unusual nucleic acid structures. The discovery that
      canonical Watson-Crick G.C or A.T hydrogen-bonded pairs can be transformed into
      stacking pairs greatly increases the repertoire for unusual nucleic acid
      structural motifs.

PMID- 11575931
TI  - Solution structure of a DNA double helix incorporating four consecutive non
      Watson-Crick base-pairs.
AB  - A series of DNA 21-mers containing a variety of the 4 x 4 internal loop sequence
      5'-CAAG-3'/3'-ACGT-5' were studied using nuclear magnetic resonance (NMR)
      methodology and distance geometry (DG)/molecular dynamics (MD) approaches. Such
      oligomers exhibit excellent resolution in the NMR spectra and reveal many unusual
      NOEs (nuclear Overhauser effect) that allow for the detailed characterization of
      a DNA hairpin incorporating a track of four different non-Watson-Crick base-pairs
      in the stem. These include a wobble C.A base-pair, a sheared A.C base-pair, a
      sheared A.G base-pair, and a wobble G.T base-pair. Significantly different
      twisting angles were observed between the base-pairs in internal loop that
      results with excellent intra-strand and inter-strand base stacking within the
      four consecutive mismatches and the surrounding canonical base-pairs. This
      explains why it melts at 52 degrees C even though five out of ten base-pairs in
      the stem adopt non-Watson-Crick pairs. However, the 4 x 4 internal loop still
      fits into a B-DNA double helix very well without significant change in the
      backbone torsion angles; only zeta torsion angles between the tandem sheared base
      pairs are changed to a great extent from the gauche(-) domain to the trans domain
      to accommodate the cross-strand base stacking in the internal loop. The
      observation that several consecutive non-canonical base-pairs can stably co-exist
      with Watson-Crick base-pairs greatly increases the limited repertoire of
      irregular DNA folds and reveals the possibility for unusual structural formation
      in the functionally important genomic regions that have potential to become
      single-stranded.

PMID- 11575932
TI  - Internalins from the human pathogen Listeria monocytogenes combine three distinct
      folds into a contiguous internalin domain.
AB  - Listeria monocytogenes is an opportunistic, food-borne human and animal pathogen.
      Host cell invasion requires the action of the internalins A (InlA) and B (InlB),
      which are members of a family of listerial cell-surface proteins. Common to these
      proteins are three distinctive N-terminal domains that have been shown to direct
      host cell-specific invasion for InlA and InlB. Here, we present the high
      resolution crystal structures of these domains present in InlB and InlH, and show
      that they constitute a single "internalin domain". In this internalin domain, a
      central LRR region is flanked contiguously by a truncated EF-hand-like cap and an
      immunoglobulin (Ig)-like fold. The extended beta-sheet, resulting from the
      distinctive fusion of the LRR and the Ig-like folds, constitutes an adaptable
      concave interaction surface, which we propose is responsible for the specific
      recognition of the host cellular binding partners during infection.

PMID- 11575933
TI  - Structural mechanisms of drug resistance for mutations at codons 181 and 188 in
      HIV-1 reverse transcriptase and the improved resilience of second generation non
      nucleoside inhibitors.
AB  - Mutations at either Tyr181 or Tyr188 within HIV-1 reverse transcriptase (RT) give
      high level resistance to many first generation non-nucleoside inhibitors (NNRTIs)
      such as the anti-AIDS drug nevirapine. By comparison second generation
      inhibitors, for instance the drug efavirenz, show much greater resilience to
      these mutations. In order to understand the structural basis for these
      differences we have determined a series of seven crystal structures of mutant RTs
      in complexes with first and second generation NNRTIs as well as one example of an
      unliganded mutant RT. These are Tyr181Cys RT (TNK-651) to 2.4 A, Tyr181Cys RT
      (efavirenz) to 2.6 A, Tyr181Cys RT (nevirapine) to 3.0 A, Tyr181Cys RT (PETT-2)
      to 3.0 A, Tyr188Cys RT (nevirapine) to 2.6 A, Tyr188Cys RT (UC-781) to 2.6 A and
      Tyr188Cys RT (unliganded) to 2.8 A resolution. In the two previously published
      structures of HIV-1 reverse transcriptase with mutations at 181 or 188 no side
      chain electron density was observed within the p66 subunit (which contains the
      inhibitor binding pocket) for the mutated residues. In contrast the mutated side
      chains can be seen in the NNRTI pocket for all seven structures reported here,
      eliminating the possibility that disordering contributes to the mechanism of
      resistance. In the case of the second generation compounds efavirenz with
      Tyr181Cys RT and UC-781 with Tyr188Cys RT there are only small rearrangements of
      either inhibitor within the binding site compared to wild-type RT and also for
      the first generation compounds TNK-651, PETT-2 and nevirapine with Tyr181Cys RT.
      For nevirapine with the Tyr188Cys RT there is however a more substantial movement
      of the drug molecule. We conclude that protein conformational changes and
      rearrangements of drug molecules within the mutated sites are not general
      features of these particular inhibitor/mutant combinations. The main contribution
      to drug resistance for Tyr181Cys and Tyr188Cys RT mutations is the loss of
      aromatic ring stacking interactions for first generation compounds, providing a
      simple explanation for the resilience of second generation NNRTIs, as such
      interactions make much less significant contribution to their binding.

PMID- 11575934
TI  - Unusual molecular architecture of the Yersinia pestis cytotoxin YopM: a leucine
      rich repeat protein with the shortest repeating unit.
AB  - Many Gram-negative bacterial pathogens employ a contact-dependent (type III)
      secretion system to deliver effector proteins into the cytosol of animal or plant
      cells. Collectively, these effectors enable the bacteria to evade the immune
      response of the infected organism by modulating host-cell functions. YopM, a
      member of the leucine-rich repeat protein superfamily, is an effector produced by
      the bubonic plague bacterium, Yersinia pestis, that is essential for virulence.
      Here, we report crystal structures of YopM at 2.4 and 2.1 A resolution. Among all
      leucine-rich repeat family members whose atomic coordinates have been reported,
      the repeating unit of YopM has the least canonical secondary structure. In both
      crystals, four YopM monomers form a hollow cylinder with an inner diameter of 35
      A. The domain that targets YopM for translocation into eukaryotic cells adopts a
      well-ordered, alpha-helical conformation that packs tightly against the proximal
      leucine-rich repeat module. A similar alpha-helical domain can be identified in
      virulence-associated leucine-rich repeat proteins produced by Salmonella
      typhimurium and Shigella flexneri, and in the conceptual translation products of
      several open reading frames in Y. pestis.

PMID- 11575935
TI  - The structure of helix III in Xenopus oocyte 5 S rRNA: an RNA stem containing a
      two-nucleotide bulge.
AB  - The solution structure of an oligonucleotide containing the helix III sequence
      from Xenopus oocyte 5 S rRNA has been determined by NMR spectroscopy. Helix III
      includes two unpaired adenosine residues, flanked on either side by G:C base
      pairs, that are required for binding of ribosomal protein L5. The consensus
      conformation of helix III in the context provided by this oligonucleotide has the
      two adenosine residues located in the minor groove and stacked upon the 3'
      flanking guanosine residue, consistent with biochemical studies of free 5 S rRNA
      in solution. A distinct break in stacking that occurs between the first adenosine
      residue of the bulge and the flanking 5' guanosine residue exposes the base of
      the adenosine residue in the minor groove and the base of the guanosine residue
      in the major groove. The major groove of the helix is widened at the site of the
      unpaired nucleotides and the helix is substantially bent; nonetheless, the G:C
      base-pairs flanking the bulge are intact. The data indicate that there may be
      conformational heterogeneity centered in the bulge region. The corresponding
      adenosine residues in the Haloarcula marismortui 50 S ribosomal subunit form a
      dinucleotide platform, which is quite different from the motif seen in solution.
      Thus, the conformation of helix III probably changes when 5 S rRNA is
      incorporated into the ribosome.

PMID- 11575936
TI  - Solution NMR structure and folding dynamics of the N terminus of a rat non-muscle
      alpha-tropomyosin in an engineered chimeric protein.
AB  - Tropomyosin is an alpha-helical coiled-coil protein that aligns head-to-tail
      along the length of the actin filament and regulates its function. The solution
      structure of the functionally important N terminus of a short 247-residue non
      muscle tropomyosin was determined in an engineered chimeric protein, GlyTM1bZip,
      consisting of the first 19 residues of rat short alpha-tropomyosin and the last
      18 residues of the GCN4 leucine zipper. A gene encoding GlyTM1bZip was
      synthesized, cloned and expressed in Escherichia coli. Triple resonance NMR
      spectra were analyzed with the program AutoAssign to assign its backbone
      resonances. Multidimensional nuclear Overhauser effect spectra, X-filtered
      spectra and (3)J(H(N)-H(alpha)) scalar coupling were analyzed using
      AutoStructure. This is the first application of this new program to determine the
      three-dimensional structure of a symmetric homodimer and a structure not
      previously reported. Residues 7-35 in GlyTM1bZip form a coiled coil, but neither
      end is helical. Heteronuclear (15)N-(1)H nuclear Overhauser effect data showed
      that the non-helical N-terminal residues are flexible. The (13)C' chemical shifts
      of the coiled-coil backbone carbonyl groups in GlyTM1bZip showed a previously
      unreported periodicity, where resonances arising from residues at the coiled-coil
      interface in a and d positions of the heptad repeat were displaced relatively
      upfield and those arising from residues in c positions were displaced relatively
      downfield. Heteronuclear single quantum coherence spectra, collected as a
      function of temperature, showed that cross-peaks arising from the alpha-helical
      backbone and side-chains at the coiled-coil interface broadened or shifted with
      T(M) values approximately 20 degrees C lower than the loss of alpha-helix
      measured by circular dichroism, suggesting the presence of a folding
      intermediate. The side-chain of Ile14, a residue essential for binding
      interactions, exhibited multiple conformations. The conformational flexibility of
      the N termini of short tropomyosins may be important for their binding
      specificity.

PMID- 11575937
TI  - Acidic conditions stabilise intermediates populated during the folding of Im7 and
      Im9.
AB  - The helical bacterial immunity proteins Im7 and Im9 have been shown to fold via
      kinetic mechanisms of differing complexity, despite having 60 % sequence
      identity. At pH 7.0 and 10 degrees C, Im7 folds in a three-state mechanism
      involving an on-pathway intermediate, while Im9 folds in an apparent two-state
      transition. In order to examine the folding mechanisms of these proteins in more
      detail, the folding kinetics of both Im7 and Im9 (at 10 degrees C in 0.4 M sodium
      sulphate) have been examined as a function of pH. Kinetic modelling of the
      folding and unfolding data for Im7 between pH 5.0 and 8.0 shows that the on
      pathway intermediate is stabilised by more acidic conditions, whilst the native
      state is destabilised. The opposing effect of pH on the stability of these states
      results in a significant population of the intermediate at equilibrium at pH 6.0
      and below. At pH 7.0, the folding and unfolding kinetics for Im9 can be fitted
      adequately by a two-state model, in accord with previous results. However, under
      acidic conditions there is a clear change of slope in the plot of the logarithm
      of the folding rate constant versus denaturant concentration, consistent with the
      population of one or more intermediate(s) early during folding. The kinetic data
      for Im9 at these pH values can be fitted to a three-state model, where the
      intermediate ensemble is stabilised and the native state destabilised as the pH
      is reduced, rationalising previous results that showed that an intermediate is
      not observed experimentally at pH 7.0. The data suggest that intermediate
      formation is a general step in immunity protein folding and demonstrate that it
      is necessary to explore a wide range of refolding conditions in order to show
      that intermediates do not form in the folding of other small, single-domain
      proteins.

PMID- 11575938
TI  - Dynamic regimes and correlated structural dynamics in native and denatured alpha
      lactalbumin.
AB  - Understanding the mechanisms of protein folding requires knowledge of both the
      energy landscape and the structural dynamics of a protein. We report a neutron
      scattering study of the nanosecond and picosecond dynamics of native and the
      denatured alpha-lactalbumin. The quasielastic scattering intensity shows that
      there are alpha-helical structure and tertiary-like side-chain interactions
      fluctuating on sub-nanosecond time-scales under extremely denaturing conditions
      and even in the absence of disulfide bonds. Based on the length-scale dependence
      of the decay rate of the measured correlation functions, the nanosecond dynamics
      of the native and the variously denatured proteins have three dynamic regimes.
      When 0.05<Q<0.5 A(-1) (where the scattering vector, Q, is inversely proportional
      to the length-scale), the decay rate, Gamma, shows a power law relationship,
      Gamma proportional to Q(2.42+/-0.08), that is analogous to the dynamic behavior
      of a random coil. However, when 0.5<Q<1.0 A(-1), the decay rate exhibits a Gamma
      proportional to Q(1.0+/-0.2) relationship. The effective diffusion constant of
      the protein decreases with increasing Q, a striking dynamic behavior that is not
      found in any chain-like macromolecule. We suggest that this unusual dynamics is
      due to the presence of a strongly attractive force and collective conformational
      fluctuations in both the native and the denatured states of the protein. Above
      Q>1.0 A(-1) is a regime that displays the local dynamic behavior of individual
      residues, Gamma proportional to Q(1.8+/-0.3). The picosecond time-scale dynamics
      shows that the potential barrier to side-chain proton jump motion is reduced in
      the molten globule and in the denatured proteins when compared to that of the
      native protein. Our results provide a dynamic view of the native-like topology
      established in the early stages of protein folding.

PMID- 11575939
TI  - Sequencing and two-dimensional structure prediction of a phospholipase A(2)
      inhibitor from the serum of the common tiger snake (Notechis scutatus).
AB  - A phospholipase A(2) inhibitor has been identified in the serum of the common
      tiger snake (Notechis scutatus). The inhibitor is composed of two chains, an
      alpha-chain and a beta-chain, that form a non-covalently associated complex
      capable of inhibiting the enzymatic activity of all phospholipase A(2) enzymes it
      was tested against. The alpha and beta-chains have been purified to homogeneity,
      digested and sequenced. From the peptide sequence generated, degenerate PCR
      primers were designed and used to elucidate the complete cDNA sequence of the
      chains using 5' and 3' RACE PCR. A total of three alpha-chain isoforms were
      identified, only one isoform of the beta-chain was detected. The two-dimensional
      structure of the three alpha-chains and one beta-chain were predicted using five
      prediction programs (discrimination of secondary structure class; nearest
      neighbour secondary structure, profile network from Heidelberg; self-optimised
      prediction method from multiple alignment, SSPAL). For each protein chain a
      consensus prediction was generated. Results are discussed in relation to the
      function of the protein, and how they may influence the three-dimensional
      structure of the inhibitor. Additionally, the sequences of several snake
      phospholipase A(2) inhibitors were used as the input for a motif prediction
      algorithm (MEME). The results are discussed in relation to the activity of these
      proteins.

PMID- 11575940
TI  - Prediction of functionally important residues based solely on the computed
      energetics of protein structure.
AB  - Catalytic and other functionally important residues in proteins can often be
      mutated to yield more stable proteins. Many of these residues are charged
      residues that are located in electrostatically unfavorable environments. Here it
      is demonstrated that because continuum electrostatics methods can identify these
      destabilizing residues, the same methods can also be used to identify
      functionally important residues in otherwise uncharacterized proteins. To
      establish this point, detailed calculations are performed on six proteins for
      which good structural and mutational data are available from experiments. In all
      cases it is shown that functionally important residues known to be destabilizing
      experimentally are among the most destabilizing residues found in the
      calculations. A larger scale analysis performed on 216 different proteins
      demonstrates the existence of a general relationship between the calculated
      electrostatic energy of a charged residue and its degree of evolutionary
      conservation. This relationship becomes obscured when electrostatic energies are
      calculated using Coulomb's law instead of the more complete continuum
      electrostatics method. Finally, in a first predictive application of the method,
      calculations are performed on three proteins whose structures have recently been
      reported by a structural genomics consortium.

PMID- 11575941
TI  - Heliotropium huascoense resin exudate: chemical constituents and defensive
      properties.
AB  - From the resinous exudate of Heliotropium huascoense a new compound, rel-(8R,9R)
      carrizaloic acid, (1) (3-[rel-(8R,9R-9-hydroxy-9,13,13-trimethyl-12-oxo-10
      cyclohexenyl)methyl]-4-methoxybenzoic acid), and three known flavonoids, [3
      methylgalangin, 3,7-dimethylgalangin, and (-)-alpinone] have been isolated. The
      structure of 1 was determined by spectral and chemical methods. Several plant
      defensive properties of 1 (insecticidal and antifungal) have been evaluated.

PMID- 11575942
TI  - New spirostanol steroids and steroidal saponins from roots and rhizomes of
      Dracaena angustifolia and their antiproliferative activity.
AB  - The MeOH extract of Nam ginseng (roots and rhizomes of Dracaena angustifolia)
      afforded nine new compounds, including three spirostanol sapogenins, named
      namogenins A-C (1-3), four spirostanol saponins, named namonins A-D (4-7), a
      furostanol saponin, named namonin E (8), and a pregnan glycoside, named namonin F
      (9), along with another eight known steroidal saponins (10-17). Their structures
      were determined on the basis of spectral analyses and chemical methods. All
      compounds were tested for their antiproliferative activity against murine colon
      26-L5 carcinoma, human HT-1080 fibrosarcoma, and B-16 BL6 melanoma cells.
      Compounds 4, 5, and 10 showed potent antiproliferative activity against HT-1080
      fibrosarcoma cells, having IC(50) values of 0.2, 0.3, and 0.6 microM,
      respectively, comparable to that of doxorubicin.

PMID- 11575943
TI  - Dysideaprolines A-F and barbaleucamides A-B, novel polychlorinated compounds from
      a Dysidea species.
AB  - Chemical investigation of a marine sponge, Dysidea sp., collected at Bararin
      Island, Philippines, has afforded the novel metabolites 1-6, proline-derived
      analogues of dysidenin (7). We have termed compounds 1-6 dysideaprolines A-F,
      respectively. Also isolated were compounds 8 and 9, structural analogues of
      barbamide (10), a metabolite originally isolated from the cyanobacterium Lyngbya
      majuscula. We have termed these novel compounds barbaleucamides A (8) and B (9).
      It is most probable that the compounds presented here are actually derived from a
      symbiotic cyanobacterium found in close association with the Dysidea sp.
      Structure elucidation of the isolated metabolites involved high-field 2D NMR
      spectroscopy including (1)H-(1)H COSY, HSQC, and HMBC.

PMID- 11575944
TI  - Structures of carotenoids with 5,6-dihydro-beta-end groups from the spindle shell
      Fusinus perplexus.
AB  - A series of pirardixanthin derivatives, 1, 2, 3, 4, and 5, possessing the 5,6
      dihydro-beta-end group were isolated from the spindle shell Fusinus
      perplexus.(1,2) Their structures and absolute configurations were determined by
      modern spectroscopic analysis to be (4S,5S,6S,4'S,5'S,6'S)-5,6,5',6'-tetrahydro
      beta,beta-carotene-4,4'-diol (1), (3S,4R,5S,6S,4'S,5'S,6'S)-5,6,5',6'-tetrahydro
      beta,beta-carotene-3,4,4'-triol (2), (3S,4R,5S,6S,3'S,4'R,5'S,6'S)-5,6,5',6'
      tetrahydro-beta,beta-carotene-3,4,3',4'-tetrol (3), (5S,6S,4'S,5'S,6'S)-4'
      hydroxy-5,6,5',6'-tetrahydro-beta,beta-caroten-4-one (4), and (4'S,5'S,6'S)-4'
      hydroxy-5',6'-dihydro-beta,beta-caroten-4-one (5).

PMID- 11575945
TI  - Quinoline alkaloids and other constituents of Melicope semecarpifolia with
      antiplatelet aggregation activity.
AB  - Three new quinoline alkaloids, 2-acetylevolitrine (1), 2-acetylpteleine (2), and
      semecarpifoline (3), along with 26 known compounds were isolated from the root
      bark of Melicope semecarpifolia. The structures of 1-3 were elucidated by means
      of spectral analysis. In addition, (2S)-(--)-7,8-dimethoxyplatydesmine (4), cis
      (+)-7,8-dimethoxymyrtopsine (5), and (3R)-(--)-8,9-dimethoxygeibalansine (6) were
      isolated as new natural products. Several of these isolates were determined as
      exhibiting significant antiplatelet aggregation activities in vitro.

PMID- 11575946
TI  - Isolation and structure of five new cancer cell growth inhibitory bufadienolides
      from the Chinese traditional drug Ch'an Su.
AB  - Five new bufadienolides, 3beta-formyloxyresibufogenin (1), 19-oxobufalin (2), 19
      oxodesacetylcinobufagin (3), 6alpha-hydroxycinobufagin (4), and 1beta
      hydroxybufalin (5), have been isolated together with the previously known
      bufadienolides 6-20 from the Chinese traditional drug "Ch'an Su". The structures
      were elucidated employing spectroscopic methods. Bufadienolides 1-5 provided
      significant inhibitory activity against the KB and HL-60 cancer cell lines. In
      addition, bufadienolide 1 was found active against the MH-60 cancer cell line.

PMID- 11575947
TI  - A new naphthopyrone derivative from Cassia quinquangulata and structural revision
      of quinquangulin and its glycosides.
AB  - A novel naphthopyrone derivative, named quinquangulone (1), has been isolated
      from Cassia quinquangulata, along with the known compounds quinquangulin (2) and
      its two glycosides (3 and 4), rubrofusarin (5) and its two glycosides (6 and 7),
      nor-rubrofusarin (8) and its 6-O-glucoside (9), and three stilbenes (10-12). The
      structure of quinquangulone was established by spectral interpretation as 5,9
      dihydroxy-8-methoxy-2,9-dimethyl-6-oxo-4H,6H,9H-naphtho-[2,3-b]pyran-4-one.
      Reinvestigation of the NMR spectra of quinquangulin led to revision of its
      structure as 5,6-dihydroxy-8-methoxy-2,9-dimethyl-4H-naphtho[2,3-b]pyran-4-one
      (2a). The structures of two quinguangulin glycosides, 3 and 4, were also revised
      accordingly. Compound 2a exhibited activity against Staphylococcus aureus and
      methicillin-resistant S. aureus (MIC, 3.125 and 6.25 microg/mL, respectively).

PMID- 11575948
TI  - The alkaloids of Artabotrys uncinatus.
AB  - A novel type of alpha,beta-butenolide alkaloid, uncinine (1), two novel
      oxoaporphines, artabonatine C (2) and artabonatine D (3), a new oxazoloaporphine,
      artabonatine E (4), and a new 7,7'-bisdehydroaporphine, artabonatine F (5), along
      with 25 known alkaloids, were isolated from Artabotrys uncinatus. The structures
      of 1-5 were determined using NMR and mass spectral data. Atherospermidine and
      squamolone exhibited cytotoxicity against hepatocarcinoma cancer cell lines (Hep
      G(2) and 2,2,15), and the activity of some of the alkaloids in an antithrombin
      assay is also discussed.

PMID- 11575949
TI  - Cytotoxicity of Rhamnosylanthraquinones and Rhamnosylanthrones from Rhamnus
      nepalensis.
AB  - An extract of the fruits of Rhamnus nepalensis collected in Hoa Binh Province,
      Vietnam, was cytotoxic to KB cells. A bioassay-guided fractionation led to the
      isolation of a series of known anthraquinones and anthrones, one new
      rhamnosylanthraquinone, 3'-O-acetylfrangulin A (8), several new
      rhamnosylanthrones, the prinoidin-emodin bianthrones (9A-D), the prinoidin
      bianthrones (10A,B), and the rhamnepalins (11A-C). A structure-cytotoxic activity
      relationship study was performed on these isolates and some semisynthetic
      derivatives.

PMID- 11575950
TI  - Haterumaimides F-I, four new cytotoxic diterpene alkaloids from an ascidian
      Lissoclinum species.
AB  - Four new monochlorinated diterpene alkaloids, haterumaimides F-I (1-4), and two
      known ones, dichlorolissoclimide and chlorolissoclimide, were isolated from an
      ascidian Lissoclinum sp. Their structures with absolute stereochemistries were
      elucidated by chemical and spectral analyses. Haterumaimides F-I (1-4) inhibited
      the first cleavage of fertilized sea urchin eggs and exhibited potent to weak
      cytotoxicities against P388 cells.

PMID- 11575951
TI  - A hemicellulose B fraction from grape skin (Vitis vinifera, Palomino variety).
AB  - The structure of a hemicellulose B fraction (B-1) isolated from grape skins
      (Vitis vinifera) of the Palomino variety has been studied by methylation
      analysis, (1)H NMR and (13)C NMR spectroscopy, and partial acid hydrolysis.
      Hemicellulose B-1 appeared to be homogeneous by gel filtration with a weight
      average molecular weight of 22 600. This polysaccharide is a linear xyloglucan
      chain composed of xylopyranosyl and glucopyranosyl residues linked by beta-(1-
      >4) glycosidic bonds. Attached to this backbone, 4-O-methyl-D-glucuronopyranosyl
      acid, D-glucopyranosyl, and L-fucopyranosyl residues occur at position 2 in a
      ratio of one residue for every five units of xylose in the main chain, with D
      xylopyranosyl residues attached at position 6 of glucose units in a ratio of one
      residue for every two glucose-derived moieties in the main chain.

PMID- 11575952
TI  - Secondary metabolites from the roots of Astragalus zahlbruckneri.
AB  - Four new phenolic glycosides, beta-apiofuranosyl-(1-->2)-beta-glucopyranosides (1
      4), along with the cycloartane triterpenes 20(R),25-epoxy
      3beta,6alpha,16beta,24alpha-tetrahydroxycycloartane (5) and 20(R),24(S)-epoxy
      3beta,6alpha,25-trihydroxycycloartan-16-one (6) were isolated from roots of
      Astragalus zahlbruckneri. The structure elucidation of all compounds was based on
      their (1)H and (13)C NMR spectral data including 1D-TOCSY, DQF-COSY, HSQC, and
      HMBC experiments.

PMID- 11575953
TI  - Sequestered chemistry of the Arminacean nudibranch Leminda millecra in Algoa Bay,
      South Africa.
AB  - Extracts of the endemic nudibranch Leminda millecra collected in Algoa Bay, South
      Africa, yielded four known metabolites, millecrones A (1) and B (2),
      isofuranodiene (5), and (+)-8-hydroxycalamenene (9), and nine new compounds,
      algoafuran (7), cubebenone (8), and a series of seven triprenylquinones and
      hydroquinones (21-27). A subsequent GC-MS survey of extracts of 21 of L.
      millecra's possible octocoral prey species in Algoa Bay identified the soft coral
      Alcyonium fauri as the source of 1 and the gorgonian Leptogorgia palma as the
      species producing 2 and 8.

PMID- 11575954
TI  - Xanthones from Garcinia parvifolia.
AB  - Nine new xanthones, parvixanthones A-I (1-9), isolated from the dried bark of
      Garcinia parvifolia, were found to have a common 1,3,6,7-oxygenated pattern for
      their xanthone nucleus, but various oxygenated isoprenyl or geranyl substituent
      groups. The structures were determined by spectroscopic methods.

PMID- 11575955
TI  - Three new sesquiterpene glycosides from Dendrobium nobile with immunomodulatory
      activity.
AB  - Dendroside A (1) and dendronobilosides A and B (2 and 3), three new sesquiterpene
      glycosides, have been isolated from the stems of Dendrobium nobile, a plant used
      in Chinese traditional medicine. Their structures and stereochemistry were
      determined as 10beta,12,14-trihydroxyalloaromadendrane 14-O-beta-D
      glucopyranoside (1), 10,12-dihydroxypicrotoxane 10,12-di-O-beta-D-glucopyranoside
      (2), and 6alpha,10,12-trihydroxypicrotoxane 10-O-beta-D-glucopyranoside (3),
      respectively, on the basis of spectroscopic and chemical methods. Quantum
      chemistry calculations were used in support of the structural determination of 1.
      Compounds 1 and 2 were found to stimulate the proliferation of murine T and B
      lymphocytes in vitro, while compound 3 showed inhibitory activity in this same
      assay.

PMID- 11575956
TI  - Synthesis of new artemisinin analogues from artemisinic acid modified at C-3 and
      C-13 and their antimalarial activity.
AB  - Artemisinic acid (2) was modified through allylic oxidation at C-3 or conjugate
      addition at C-13 to afford 12 methyl artemisinate derivatives (4-15).
      Photooxidation of the derivatives yielded eight new artemisinin analogues,
      including 13-cyanoartemisinin (16), 13-methoxycarbonyl artemisinin (17), 13
      methoxyartemisinin (18), 13-ethylsulfonylartemisinin (19), 13
      nitromethylartemisinin (20), 13-(1-nitroethyl)artemisinin (21), (3R)-3
      hydroxyartemisinin (22), and (3R)-3-acetoxyartemisinin (23). Among the analogues,
      only compound 20 had antimalarial activity comparable to artemisinin (1).

PMID- 11575957
TI  - Five new diprenylated flavonols from the leaves of Broussonetia kazinoki.
AB  - Five new diprenylated flavonols, broussonol A (1), broussonol B (2), broussonol C
      (3), broussonol D (4), and broussonol E (5), along with two known compounds, were
      isolated from an ethanolic extract of the leaves of Broussonetia kazinoki. Their
      structures were elucidated by chemical and spectral methods. Cytotoxic activities
      were evaluated against several different cell lines.

PMID- 11575958
TI  - Sex pheromones of the hair crab Erimacrus isenbeckii. II. Synthesis of ceramides.
AB  - To confirm their structures and to assess the pheromonal activity, novel
      ceramides, possible sex pheromones of the hair crab Erimacrus isenbeckii, were
      synthesized from D-galactose. The synthetic ceramides were identical with the
      natural ceramides.

PMID- 11575959
TI  - Rocaglamides, glycosides, and putrescine bisamides from Aglaia dasyclada.
AB  - A phytochemical analysis of the leaves of Aglaia dasyclada collected in Yunnan
      Province (People's Republic of China) yielded five cyclopentabenzofurans (1-5) of
      the rocaglamide family that are common secondary metabolites of Aglaia species as
      well as four biogenetically related compounds of the aglain (7), aglaforbesin (8)
      and forbaglin (9, 10) types. In addition, the cinnamic acid amide dasyclamide
      (6), which is a putative biogenetic precursor of these compounds (7-10), was
      isolated. The structures of the new compounds (6-10) were assigned unambiguously
      from the combined use of 1D and 2D NMR spectroscopy and mass spectrometry.

PMID- 11575960
TI  - Bioactive acridone alkaloids from Swinglea glutinosa.
AB  - A new prenylated acridone alkaloid, 1,3,5-trihydroxy-2,8-bis(3-methylbut-2-enyl)
      10-methyl-9-acridone (1), was isolated from the stembark of Swinglea glutinosa,
      along with three known acridone alkaloids, 5-hydroxynoracronycine (2), 1,3,5
      trihydroxy-4-methoxy-2-(3-methylbut-2-enyl)-10-methyl-9-acridone (3), and 1,3,5
      trihydroxy-4-methoxy-10-methylacridone (4). The isolated alkaloids were assessed
      in vitro against chloroquine-sensitive and -resistant Plasmodium falciparum
      strains and for cytotoxicity using HeLa cells.

PMID- 11575961
TI  - Isolation and characterization of two new alkaloids, norpandamarilactonine-A and 
      B, from Pandanus amaryllifolius by spectroscopic and synthetic methods.
AB  - Two new alkaloids, norpandamarilactonine-A (1) and -B (2), which have a
      pyrrolidinyl-alpha,beta-unsaturated gamma-lactone moiety as in the known
      pandamarilactonine alkaloids, were isolated from the leaves of Pandanus
      amaryllifolius. Their structures were determined by spectroscopic analysis and
      total synthesis.

PMID- 11575962
TI  - New bisdesmosidic triterpene saponins from the roots of Pulsatilla chinensis.
AB  - Further phytochemical analysis aimed at the triterpene saponin constituents of
      the roots of Pulsatilla chinensis has resulted in the isolation of four new
      bisdesmosidic triterpene saponins whose aglycons are based on the lupane skeleton
      (1-4), together with three known saponins (5-7). The structures of the new
      compounds were determined by spectroscopic analysis and acid-catalyzed
      hydrolysis.

PMID- 11575963
TI  - Suillusin, a unique benzofuran from the mushroom Suillus granulatus.
AB  - A unique benzofuran named suillusin was isolated from the methanolic extract of
      the fruiting body of the mushroom Suillus granulatus. Its structure was assigned
      on the basis of various spectroscopic analyses as a highly substituted novel 1H
      cyclopenta[b]benzofuran (1). Suillusin is suggested to be biogenerated from
      polyporic acid.

PMID- 11575964
TI  - Cytotoxic and novel compounds from Solanum indicum.
AB  - Solavetivone (1), cytotoxic to OVCAR-3 cells with an IC(50) value of 0.1 mM, has
      been isolated from Solanum indicum. In addition, a novel solafuranone (2) and
      three known compounds, scopoletin, N-(p-trans-coumaroyl)tyramine, and N-trans
      feruloyltyramine, were isolated for the first time from this plant. The
      structures of the above compounds were established by means of spectroscopic and
      X-ray analyses.

PMID- 11575965
TI  - Immunomodulatory constituents from an Ascomycete, Eupenicillium crustaceum, and
      revised absolute structure of macrophorin D.
AB  - Fractionation guided by immunomodulatory activity of the EtOAc extract of the
      Ascomycete Eupenicillium crustaceum has afforded two new naturally occurring
      products, 4'-oxomacrophorin D (1) and 4'-oxomacrophorin A (2), as the
      immunosuppressive components of this fungus [1: 3-hydroxy-3-methylglutaryl (HMG)
      conjugate of 2]. The structures including the absolute configurations of 1 and 2
      have been determined on the basis of chemical correlation of 1 with macrophorin D
      (3). The absolute configuration of the HMG moiety in 3 has been revised from 3R
      to 3S.

PMID- 11575966
TI  - Coumarins with monoamine oxidase inhibitory activity and antioxidative coumarino
      lignans from Hibiscus syriacus.
AB  - A previously undescribed coumarin and a new coumarino-lignan, together with the
      known compounds scopoletin and cleomiscosins A, C, and D, have been isolated from
      the root bark of Hibiscus syriacus, and their structures were assigned on the
      basis of various spectral studies. The coumarin analogue and scopoletin inhibited
      monoamine oxidase with moderate IC(50) values. The new coumarino-lignan and
      cleomiscosin C showed lipid peroxidation inhibitory activity comparable to
      vitamin E.

PMID- 11575967
TI  - Junceol A, a new sesquiterpenoid from the sea pen Virgularia juncea.
AB  - A new sesquiterpenoid, junceol A(1), as well as two known diterpenoids,
      sclerophytin A (2) and cladiellisin (3), have been isolated from the sea pen
      octocoral Virgularia juncea. The structure of metabolite 1 was determined by
      extensive spectral analysis. Compounds 1-3 have been shown to exhibit
      cytotoxicity toward P-388 cancer cells.

PMID- 11575968
TI  - New multiflorane-type triterpenoid acids from Sandoricum indicum.
AB  - Three new 12beta-hydroxymultiflorane triterpenoid acids, sandorinic acids A-C (1
      3), were isolated from the stem bark of Sandoricum indicum together with five
      known triterpenes (4-8). The structures of 1-3 were elucidated by spectral data
      interpretation. Compounds 1-8 were evaluated for their inhibiting activity
      against several tumor cell lines and for their effects on lymphocyte
      proliferation.

PMID- 11575969
TI  - Novel ceramides from the fungus Lactarium volemus.
AB  - Two novel ceramides, lactariamides A (N-2'-hydroxytetracosanoyl-2-amino-3,4
      epoxyoctadecan-1-ol (1)) and B ((4E,8E)-N-2'-hydroxyoctadecanoyl-2-amino-9-methyl
      4,8-octadecadine-1,3-diol (2)), were isolated from the fungus Lactarium volemus,
      together with a known compound, cerebroside D (3). Their structures were
      determined on the basis of chemical evidence and spectral methods.

PMID- 11575970
TI  - A new isoquinoline alkaloid from the marine sponge Haliclona species.
AB  - Two isoquinoline alkaloids, including the new compound 1, were isolated from the
      cytotoxic fractions of an aqueous extract of the marine sponge Haliclona sp. The
      structures of these compounds were established as 1-hydroxymethyl-7
      methoxyisoquinolin-6-ol (1) and mimosamycin (2) by conventional spectroscopic
      methods and by comparison with related compounds. Mimosamycin (2) was the
      principal cytotoxin with an IC(50) of approximately 10 microg/mL against melanoma
      and ovarian human tumor cell lines.

PMID- 11575971
TI  - Scorpinone: a new natural azaanthraquinone produced by a Bispora-like tropical
      fungus.
AB  - Scorpinone (1), 3-methyl-6,8-methoxy-2-aza-9,10-anthraquinone, has been isolated
      from the mycelium of a cultured sterile fungus of Caribbean origin. The structure
      was elucidated by X-ray crystallography, and 2D NMR spectral data have been
      assigned. The compound is one of very few known fungal azaanthraquinones.

PMID- 11575972
TI  - (9Z)-capsanthin-5,6-epoxide, a new carotenoid from the fruits of Asparagus
      falcatus.
AB  - From the fruits of Asparagus falcatus a novel minor (Z)-carotenoid has been
      isolated and, on the basis of spectral data interpretation, characterized as (9Z)
      capsanthin-5,6-epoxide [(9Z,3S,5R,6S,3'S,5'R)-5,6-epoxy-3,3'-dihydroxy-5,6
      dihydro-beta,kappa-caroten-6'-one, (1)]. In addition, seven other (Z)-carotenoids
      [namely, (9Z)-, (9'Z)-, (13Z)-, and (13'Z)-capsanthins, (9Z)- and (13Z)
      capsorubins, and (9Z)-violaxanthin], which have been previously described from
      other plants, were isolated and identified.

PMID- 11575973
TI  - Improving access to care for the underserved: state-supported volunteerism as a
      successful component.

PMID- 11575974
TI  - The fats of life: the role of omega-3 fatty acids in the prevention of coronary
      heart disease.
AB  - Epidemiological and clinical trial evidence suggests that omega-3 polyunsaturated
      fatty acids (PUFAs) might have a significant role in the prevention of coronary
      heart disease. Dietary sources of omega-3 PUFA include fish oils rich in
      eicosapentaenoic acid and docosahexaenoic acid along with plants rich in alpha
      linolenic acid. Randomized clinical trials with fish oils (eicosapentaenoic acid
      and docosahexaenoic acid) and alpha-linolenic acid have demonstrated reductions
      in risk that compare favorably with those seen in landmark secondary prevention
      trials with lipid-lowering drugs. Several mechanisms explaining the
      cardioprotective effect of omega-3 PUFAs have been suggested, including
      antiarrhythmic, hypolipidemic, and antithrombotic roles. Although official US
      guidelines for the dietary intake of omega-3 PUFAs are not available, several
      international guidelines have been published. Fish is an important source of
      omega-3 PUFAs in the US diet; however, vegetable sources, including grains and
      oils, offer an alternative source for those who are unable to regularly consume
      fish.

PMID- 11575975
TI  - An evaluation of Choose to Move 1999: an American Heart Association physical
      activity program for women.
AB  - BACKGROUND: Rates of physical inactivity and poor nutrition, which are 2 of the
      most important modifiable risk factors for cardiovascular disease in women, are
      substantial. Even so, studies of interventions designed to improve lifestyle
      behaviors in women have been limited and often confined to particular
      geographical areas. OBJECTIVE: To evaluate the effect of Choose to Move on
      increasing women's physical activity, improving their knowledge of heart disease
      and stroke, and improving their nutrition. PARTICIPANTS AND METHODS: A
      prospective, nonrandomized, 12-week educational intervention designed by the
      American Heart Association for women across the United States. Participants
      received a welcome kit and manual with weekly information about how to manage
      cardiovascular disease risk factors and how to build a support system for
      lifestyle change. Women (N = 23 171) aged 25 years or older were recruited by
      direct mail, the media, health care providers, and other means. Follow-up
      evaluations were returned from 6389 women at 2 weeks, 5338 at 4 weeks, 4209 at 8
      weeks, 3916 at 10 weeks, and 3775 at 12 weeks. Participants self-reported their
      physical activity, diet, and knowledge about heart disease, stroke, and related
      symptoms. RESULTS: Ninety percent of the participants were white and 56% were
      aged between 35 and 54 years. Among the participants who completed the week 12
      follow-up evaluation, the percentage who reported being active (at least moderate
      exercise > or =5 times per week or >2(1/2) hours per week for the past 1 to 6
      months) increased from 32% at baseline to 67% at the program's end (P =.001).
      Participants currently limiting excess calories or fat increased from 72% to 91%
      at week 10 follow-up evaluation (P =.001). The proportion correctly identifying
      heart disease as the leading cause of death increased from 84% to 91% at week 10
      follow-up evaluation (P<.001). CONCLUSIONS: Women who completed the Choose to
      Move program evaluation reported that they significantly increased their levels
      of physical activity, reduced their consumption of high-fat foods, and increased
      their knowledge and awareness of cardiovascular disease risk and its symptoms.
      This program provides an important model for public health, voluntary, and other
      health organizations of population-based, targeted low-cost self-help programs
      that support the Healthy People 2010 objectives for physical activity, nutrition,
      and cardiovascular health.

PMID- 11575976
TI  - Gallstone disease and related risk factors in patients with Crohn disease:
      analysis of 330 consecutive cases.
AB  - BACKGROUND: The reported prevalence of gallstone disease (GD), defined as current
      gallstones or previous cholecystectomy for gallstones, in patients with Crohn
      disease ranges from 13% to 34%. The aim of this study was to characterize the
      still undefined risk factors of this complication. METHODS: A total of 330
      consecutive patients with Crohn disease (189 males and 141 females aged 17-82
      years, mean +/- SD age, 41 +/- 14 years) underwent liver ultrasonography.
      RESULTS: A diagnosis of GD was made in 78 patients (24%), 54 with current
      gallstones and 24 who had undergone previous cholecystectomy. Its frequency was
      comparable in males and females (23% vs 25%), but was significantly associated
      with age (P =.001), being 13%, 36%, and 51% in patients aged 44 years and
      younger, 45 to 59 years, and 60 years and older, respectively (P =.001). Its
      prevalence significantly differed according to the site of the disease at
      diagnosis (P =.02) and was unrelated to disease duration. Gallstone disease was
      more frequent in patients who had undergone surgery (34% vs 14%; P =.001) and was
      significantly associated with the number (P =.001) and site of bowel resections
      (P =.001), increasing from 28% in the patients who had undergone 1 resection to
      53% in those having had 2 or more resections (P =.005) and being significantly
      higher in patients with a resection involving the ileocecal region. Multivariate
      analysis showed that age; site of disease at diagnosis; and the presence, number,
      and site of bowel resections were significantly related to GD. CONCLUSIONS: In
      patients with Crohn disease, the frequency of GD is significantly higher than
      that reported in the general population with comparable characteristics (z =
      5.04, P<.001). Age; site of disease at diagnosis; and the history, number, and
      site of bowel resections are independently associated with GD.

PMID- 11575977
TI  - Is "isolated home" hypertension as opposed to "isolated office" hypertension a
      sign of greater cardiovascular risk?
AB  - BACKGROUND: The SHEAF (Self-Measurement of Blood Pressure at Home in the Elderly:
      Assessment and Follow-up) study is an observational study (from February 1998 to
      early 2002) designed to determine whether home blood pressure (BP) measurement
      has a greater cardiovascular prognostic value than office BP measurement among
      elderly (> or =60 years) French patients with hypertension. The objective of this
      present work is to describe the baseline characteristics of the treated patients
      in the SHEAF study from February 1998 to March 1999, placing special emphasis on
      "isolated office" and "isolated home" hypertension. METHODS: Baseline office BP
      measurement was assessed using a mercury sphygmomanometer. Home BP measurement
      was performed over a 4-day period. A 140/90-mm Hg threshold was chosen to define
      office hypertension, and a 135/85-mm Hg threshold to define home hypertension.
      RESULTS: Of the 5211 hypertensive patients in the SHEAF study with a valid home
      BP measurement, 4939 received treatment with at least 1 antihypertensive drug.
      Patients with isolated office hypertension represented 12.5% of this population,
      while patients with isolated home hypertension represented 10.8%. The
      characteristics of the patients with isolated office hypertension were similar to
      those of patients with controlled hypertension. However, patients with isolated
      office hypertension had fewer previous cardiovascular complications. In contrast,
      rates of cardiovascular risk factors and history of cardiovascular disease in
      patients with isolated home hypertension resembled those in patients with
      uncontrolled hypertension. CONCLUSIONS: This retrospective analysis suggests that
      patients with isolated home hypertension belong to a high-risk subgroup. The 3
      year follow-up of these patients will provide prospective data about the
      cardiovascular prognosis of these subgroups.

PMID- 11575978
TI  - Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as
      prophylaxis against venous thromboembolism after total knee replacement: a phase
      2 dose-finding study.
AB  - BACKGROUND: Up to one third of patients who undergo total knee replacement
      develop deep vein thrombosis after surgery despite receiving low-molecular-weight
      heparin prophylaxis. Ximelagatran is a novel direct inhibitor of free and clot
      bound thrombin. METHODS: We performed a randomized, parallel, dose-finding study
      of 600 adults undergoing elective total knee replacement at 68 North American
      hospitals to determine the optimum dose of ximelagatran to use as prophylaxis
      against venous thromboembolism after total knee replacement. Patients received
      either ximelagatran twice daily by mouth in blinded fixed doses of 8, 12, 18, or
      24 mg or open-label enoxaparin sodium, 30 mg, subcutaneously twice daily,
      starting 12 to 24 hours after surgery and continuing for 6 to 12 days. We
      measured the 6- to 12-day cumulative incidence of symptomatic or venographic deep
      vein thrombosis, symptomatic pulmonary embolism, and bleeding. RESULTS: A total
      of 594 patients received at least 1 dose of the study drug; 443 patients were
      evaluable for efficacy. Rates of overall venous thromboembolism (and proximal
      deep vein thrombosis or pulmonary embolism) for the 8-, 12-, 18-, and 24-mg doses
      of ximelagatran were 27% (6.6%), 19.8% (2.0%), 28.7% (5.8%), and 15.8% (3.2%),
      respectively. Rates of overall venous thromboembolism (22.7%) and proximal deep
      vein thrombosis or pulmonary embolism (3.1%) for enoxaparin did not differ
      significantly compared with 24-mg ximelagatran (overall difference, -6.9%; 95%
      confidence interval, -18.0% to 4.2%; P=.3). There was no major bleeding with
      administration of 24 mg of ximelagatran twice daily. CONCLUSION: Fixed-dose,
      unmonitored ximelagatran, 24 mg twice daily, given after surgery appears to be
      safe and effective oral prophylaxis against venous thromboembolism after total
      knee replacement.

PMID- 11575979
TI  - The benefit of implementing a heart failure disease management program.
AB  - BACKGROUND: To handle the increasing complexity of congestive heart failure (CHF)
      care, several new models for the care of patients with CHF have been developed to
      replace traditional strategies. We undertook this study to evaluate the potential
      benefit of implementing a CHF disease management program at a tertiary care
      center, particularly in terms of beta-blocker use and cost to the health care
      system. METHODS: After reviewing the literature regarding therapies and
      management strategies for patients with CHF, we developed the Duke Heart Failure
      Program. All enrolled patients had 1 of the following: recent CHF
      hospitalization, ejection fraction less than 20%, or symptoms consistent with New
      York Heart Association class III or IV. We compared preenrollment and
      postenrollment medication use and resource utilization. RESULTS: We enrolled 117
      patients from July 1998 to April 1999. Mean enrollment time was 4.7 months. beta
      Blocker use and dose significantly increased (52% vs 76% for beta-blocker, P<.01;
      6% vs 13% of target dose, P<.01). The hospitalization rate decreased (1.5 vs 0
      hospitalizations per patient-year, P<.01), while the number of clinic visits
      increased (4.3 vs 9.8 clinic visits per patient-year, P<.01). The Duke University
      Health System saved a median of $8571 per patient-year. CONCLUSIONS: Implementing
      a CHF disease management program was associated with improved CHF medication
      dosing and with decreased hospitalization for patients with CHF. A CHF disease
      management program is an effective method for a health care system to care for
      patients with CHF.

PMID- 11575980
TI  - Costs of hepatitis C.
AB  - OBJECTIVE: To estimate the direct and indirect costs of the hepatitis C virus
      (HCV) in the United States in 1997. DESIGN: Aggregation and analysis of national
      data sets collected by the National Center for Health Statistics, the Health Care
      Financing Administration, and other government bureaus and private firms. To
      estimate costs, we used the human capital method, which decomposes costs into
      direct categories, such as medical expenses, and indirect categories, such as
      lost earnings and lost home production. We consider HCV that results in chronic
      liver disease separate from HCV that results in primary liver cancer. RESULTS: We
      estimate $5.46 billion as the cost of HCV in 1997. Costs are split as follows:
      33% for direct and 67% for indirect costs. Hepatitis C virus that results in
      chronic liver disease contributes roughly 92% of the costs, and HCV that results
      in primary liver cancer contributes the remaining 8%. The total estimate of $5.46
      billion is conservative, because we ignore costs associated with pain and
      suffering and the value of care rendered by family members. CONCLUSIONS: To our
      knowledge, only one estimate of the annual costs of HCV in the 1990s has appeared
      in the literature, $0.6 billion. However, that estimate was not supported by an
      explanation of the methods. Our estimate, which relies on detailed methods, is
      nearly 10 times the original estimate. Our estimate of $5.46 billion is on a par
      with the cost of asthma ($5.8 billion [1994]).

PMID- 11575981
TI  - Comparison of exercise test scores and physician estimation in determining
      disease probability.
AB  - BACKGROUND: The recent American College of Cardiology/American Heart Association
      exercise testing guidelines provided equations to calculate treadmill scores and
      recommended their use to improve the predictive accuracy of the standard exercise
      test. However, if physicians can estimate the probability of coronary artery
      disease as well as the scores can, there would be no reason to add this
      complexity to test interpretation. To compare the exercise test scores with
      physician's estimation of disease probability, we used clinical, exercise test,
      and coronary angiographic data to compute the recommended scores and print
      patient summaries and treadmill reports. OBJECTIVE: To determine whether exercise
      test scores can be as effective as expert cardiologists in diagnosing coronary
      disease. METHODS: Five hundred ninety-nine consecutive male patients without
      previous myocardial infarction with a mean +/- SD age of 59 +/- 11 years were
      considered for this analysis. With angiographic disease defined as any coronary
      lumen occlusion of 50% or more, 58% had disease. The clinical/treadmill test
      reports were sent to expert cardiologists and to 2 other groups, including
      randomly selected cardiologists and internists, who classified the patients as
      having high, low, or intermediate probability of disease and estimated a
      numerical probability from 0% to 100%. RESULTS: Forty-five expert cardiologists
      returned estimates on 336 patients, 37 randomly chosen practicing cardiologists
      returned estimates on 129 patients, 29 randomly chosen practicing internists
      returned estimates on 106 patients, 13 academic cardiologists returned estimates
      on 102 patients, and 27 academic internists returned estimates on 174 patients.
      When probability estimates were compared, the scores were superior to all
      physician groups (0.76 area under the receiver operating characteristic curve to
      0.70 for experts [P=.046], 0.73 to 0.58 for cardiologists [P=.003], and 0.76 to
      0.61 for internists [P=.006]). Using a probability cut point of greater than 70%
      for abnormal, predictive accuracy was 69% for scores compared with 64% for
      experts, 63% to 62% for cardiologists, and 70% to 57% for internists. CONCLUSION:
      Although most similar to the disease estimates of the presence of clinically
      significant angiographic coronary artery disease provided by the expert
      cardiologists, the scores outperformed the nonexpert physicians.

PMID- 11575982
TI  - Effect of maximal daily doses of acetaminophen on the liver of alcoholic
      patients: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Retrospective reports suggest that therapeutic doses of acetaminophen
      may be associated with fulminant hepatic failure and death in alcoholic patients.
      Millions of patients use acetaminophen; the prevalence of alcoholism in the
      United States is 5% to 10%. OBJECTIVE: To determine if hepatic injury was
      associated with maximal therapeutic dosing of acetaminophen to chronic alcohol
      abuse patients immediately following cessation of alcohol intake (the presumed
      time of maximal vulnerability). METHODS: Patients entering an alcohol
      detoxification center were enrolled in a randomized, double-blind, placebo
      controlled trial. Exclusion criteria were baseline values of aspartate or alanine
      aminotransferase greater than 120 U/L, international normalized ratio greater
      than 1.5, serum acetaminophen level greater than 20 mg/L, or a history of
      ingesting more than 4 g/d of acetaminophen. Acetaminophen, 1000 mg, or placebo
      was administered orally 4 times daily for 2 consecutive days and liver test
      results were monitored for 2 more days. Acetaminophen was not administered until
      the alcohol had been eliminated. RESULTS: There were 102 patients in the
      acetaminophen-treated group and 99 patients in the placebo-treated (control)
      group. Demographic data, alcohol history, and baseline blood test results were
      similar in both groups. The mean (SD) aspartate aminotransferase level on day 4
      was 38.0 +/- 26.7 U/L in the acetaminophen-treated group and 37.5 +/- 27.6 U/L in
      the placebo-treated group. There were 4 patients in the acetaminophen-treated
      group and 5 in the placebo-treated group who developed an increase in their serum
      aspartate aminotransferase level to greater than 120 U/L; it did not exceed 200
      U/L in any patient. The mean (SD) international normalized ratio on day 4 was
      0.96 +/- 0.09 in the acetaminophen-treated group and 0.98 +/- 0.11 in the placebo
      treated group. CONCLUSION: Repeated administration of the maximum recommended
      daily doses of acetaminophen to long-term alcoholic patients was not associated
      with evidence of liver injury.

PMID- 11575984
TI  - Primary infection with a multidrug-resistant HIV-1 strain.

PMID- 11575983
TI  - Transmission of Mycobacterium tuberculosis through casual contact with an
      infectious case.
AB  - BACKGROUND: An ongoing restriction fragment length polymorphism study of
      Mycobacterium tuberculosis isolates from tuberculosis cases showed an identical
      12-band IS6110 pattern unique to 3 unrelated patients (Patients A-C) diagnosed as
      having tuberculosis within a 9-month period. METHODS: In an attempt to identify
      epidemiologic links between the 3 patients, we performed site visits to the
      retail business work site of patient A and conducted detailed interviews with all
      3 patients and their contacts. RESULTS: Patient B had visited patient A's work
      site 3 times during patient A's infectious period, spending no more than 15
      minutes each time. Patient C visited patient A's work site on 6 to 10 occasions
      during this period for no more than 45 minutes at any one time. There were no
      other epidemiologic links between these 3 cases other than the contact at the
      store. Contact investigation identified 4 tuberculin skin test conversions among
      8 (50%) of patient A's coworkers, 6 positive tests among 15 household contacts
      (40%), and 8 positive tests among 16 identified customers who were casual
      contacts (50%). Patient B and patient C were most likely infected by patient A
      during one of their brief visits to patient A's work site. CONCLUSIONS: These
      data demonstrate that some tuberculosis is spread through casual contact not
      normally pursued in traditional contact investigations and that, in certain
      situations, M tuberculosis can be transmitted despite minimal duration of
      exposure. In addition, this outbreak emphasizes the importance of DNA
      fingerprinting data for identifying unusual transmission in unexpected settings.

PMID- 11575985
TI  - Quadricyclic antidepressant overdosage in a patient with AIDS under mega-highly
      active antiretroviral therapy.

PMID- 11575986
TI  - Myoclonus and generalized seizures associated with gatifloxacin treatment.

PMID- 11575987
TI  - Retinal vasculitis and vitreitis in a patient with chronic hepatitis C virus.

PMID- 11575988
TI  - Anaphylactic reaction to ondansetron.

PMID- 11575989
TI  - Another look at the impact of a disease management on the outcomes of patients
      with congestive heart failure.

PMID- 11575990
TI  - Impact of a guideline-based management on outcomes of very old persons with heart
      failure living in nursing homes.

PMID- 11575992
TI  - Color blindness and health care personnel.

PMID- 11575993
TI  - Color-blind physicians and the detection of blood in body products.

PMID- 11575994
TI  - Vision impairment and health.

PMID- 11575996
TI  - Fluconazole and Candida krusei fungemia.

PMID- 11575998
TI  - Shame on who?

PMID- 11576000
TI  - Writing for publication in Archives of pediatrics & adolescent medicine.

PMID- 11576001
TI  - The questions we need to ask now.

PMID- 11576002
TI  - Should watchful waiting be used more often for acute otitis media?

PMID- 11576003
TI  - Improving survival of vulnerable infants increases neonatal intensive care unit
      nosocomial infection rate.
AB  - OBJECTIVE: To determine the factors associated with an increasing rate of
      nosocomial infections in infants with very low birth weights. METHODS:
      Retrospective review of clinical and nosocomial infection databases for all
      infants with birth weights of 1500 g or less admitted to an academic neonatal
      intensive care unit between January 1, 1991, and December 31, 1997 (N = 1184).
      Two study periods were compared: 1991-1995 and 1996-1997. RESULTS: Among the 1085
      infants who survived beyond 48 hours, the proportion who developed nosocomial
      infections increased from 22% to 31% (P =.001) and the infection rate increased
      from 0.5 to 0.8 per 100 patient-days (P<.001) during the period from 1996 to
      1997. In that same period, the median duration of indwelling vascular access
      increased from 10 to 16 days (P<.001), and the median duration of mechanical
      ventilation increased from 7 to 12 days (P<.001). Although the device-specific
      rate of bloodstream or respiratory infections did not change, the increase in
      infections was directly attributable to the increasing proportion of infants who
      required these devices. In both study periods, the peak incidence of initial
      infection occurred between 10 and 20 days of age. For the entire sample,
      proportional hazard models identified birth weight, duration of vascular access,
      and postnatal corticosteroid exposure as significant contributors to the risk of
      infection. CONCLUSIONS: The increasing number of technology-dependent infants was
      the primary determinant in the increase of nosocomial infections. Because these
      infections occur in a small proportion of infants, understanding the host factors
      that contribute to this vulnerability is necessary to decrease nosocomial
      infections in neonatal intensive care units.

PMID- 11576004
TI  - Hospitalizations for pediatric intoxication in Washington State, 1987-1997.
AB  - BACKGROUND: Intoxication (or poisoning) that necessitates hospitalization remains
      an important source of morbidity in children. OBJECTIVE: To determine changes,
      during an 11-year period (1987-1997), in the incidence of hospitalization due to
      intoxication among children in Washington State and circumstances of ingestion,
      agents used, hospital length of stay, charges, and mortality. METHODS: A
      computerized database of all hospital discharges (Comprehensive Hospital Abstract
      Reporting System [CHARS] database) in Washington was used. Cases included all
      children younger than 19 years with a primary or secondary diagnosis for an
      intoxication or with an external cause of injury code (E code) for an
      intoxication from 1987 to 1997. RESULTS: There were 7322 hospitalizations (45 per
      100 000 children per year); the annual rate significantly decreased during the
      study period. Most patients (75%) were teenagers. Sixty-five percent were female.
      Pharmaceutical agents were used in 80% of cases. Analgesics were the most
      commonly used (34%), followed by antidepressants (12%) and psychotropic drugs
      (8%). Nonpharmaceutical agents were more prevalent in children younger than 12
      years than in teenagers. Self-inflicted intoxication was the most frequent cause
      identified by E codes (47%). Median length of stay was 1 day, and median hospital
      charges were $2096. Mortality was low (0.2%) and did not change significantly
      over time. CONCLUSIONS: Acute intoxication continues to be an important cause of
      hospitalization in children. The type of agent involved did not change
      significantly over time. Teenage girls continue as the highest risk group for
      suicide attempt from ingestions. Self-inflicted intoxications were associated
      with higher costs, length of stay, and readmissions. Although preventive measures
      and development of poison centers have contributed to decrease mortality from
      acute intoxication in children in the last 50 years, efforts need to be targeted
      toward suicide prevention, especially among teenage girls.

PMID- 11576005
TI  - Corticosteroid prescription filling for children covered by Medicaid following an
      emergency department visit or a hospitalization for asthma.
AB  - OBJECTIVE: To identify predictors of corticosteroid prescription filling
      following an emergency department (ED) visit or a hospitalization for asthma.
      DESIGN: A retrospective cohort study. PATIENTS: Tennessee children (defined as
      those aged 2-17 years in this study) covered by Medicaid were included in the
      cohort if they had an ED visit or a hospitalization for asthma between July 1,
      1995, and December 31, 1997. MAIN OUTCOME MEASURES: Prescriptions filled in the
      child's name for an oral corticosteroid within 7 days of the latest ED visit or
      hospitalization for asthma. RESULTS: Of 6035 Tennessee children covered by
      Medicaid with an ED visit for asthma and of 2102 covered by Medicaid with a
      hospitalization for asthma during the study period, less than half (44.8%
      following an ED visit and 55.5% following a hospitalization) had prescriptions
      filled for oral corticosteroids within 7 days. Factors independently predicting a
      child's not having an oral corticosteroid prescription filled included older age,
      black race, and residence in rural regions of the state. Conversely, children
      with oral corticosteroid prescriptions in the previous 6 months were more likely
      to have oral corticosteroid prescriptions filled following an ED visit for
      asthma, and children with more than 3 beta-agonist prescriptions in the previous
      6 months were more likely to have oral corticosteroid prescriptions filled
      following a hospitalization for asthma. CONCLUSIONS: Overall, fewer than half of
      Tennessee children covered by Medicaid had an oral corticosteroid prescription
      filled following an ED visit or a hospitalization for asthma. Age, race, and
      county of residence predicted failure to have a prescription filled. Further
      study is needed to determine whether variations in corticosteroid prescription
      filling relate to physician practice, family behavior, or both.

PMID- 11576006
TI  - Long-term effects of a middle school- and high school-based human
      immunodeficiency virus sexual risk prevention intervention.
AB  - OBJECTIVE: To determine the longer-term effect (mean +/- SD, 41.2 +/- 15.3 weeks;
      range, 14.1-80.5 weeks) of a middle school (MS)- and high school (HS)-based human
      immunodeficiency virus and sexuality intervention (Rochester AIDS Prevention
      Project for Youth [RAPP]) on knowledge, self-efficacy, behavior intention, and
      behaviors. DESIGN: Quasi-experimental design with 3 intervention groups and 1
      control group. SETTING: Urban, predominantly ethnic, minority MS and HS health
      classes. PARTICIPANTS: Middle school and HS students (N = 4001) enrolled in
      health classes in 10 schools. Fifty percent were African American; 16%, Hispanic;
      20%, white; and 14%, other. Less than 10% of the students refused participation.
      INTERVENTIONS: There were 4 study conditions: (1) control, usual health education
      curriculum taught by a classroom teacher; (2) RAPP adult health educator,
      intervention curriculum implemented by highly trained health educators; (3) RAPP
      peer educator, intervention implemented by extensively trained HS students; and
      (4) a comparison of the RAPP intervention curriculum taught by regular health
      teachers, implemented with MS students only. MAIN OUTCOME MEASURE: A confidential
      questionnaire was administered to all study subjects before and at long-term
      follow-up after the intervention, containing scales to measure knowledge, self
      efficacy, behavior intention, and behaviors, including onset of sexual
      intercourse experience and engagement in risky sexual behaviors. RESULTS: Rates
      of baseline sexual activity in the sample were comparable to those found in other
      urban school-based surveys. Long-term knowledge (MS females, P<.001; and MS
      males, P<.01) and sexual self-efficacy (MS females, P<.05; and HS females, P<.01)
      scores were higher among the intervention groups (male and female are used in
      this study to describe those aged 9(1/2)-23 years). Intention to remain safe
      regarding sexual behavior was also greater among intervention groups in MS but
      not HS. However, subjects who were already sexually active at pretest were less
      likely to show a positive intervention effect. An intervention effect for the
      onset of intercourse and risky sexual behavior was found most significantly among
      MS females. CONCLUSIONS: A positive long-term effect from the RAPP intervention
      was observed, particularly for youth who were involved in less risk (eg, not yet
      sexually active) at study enrollment. Thus, we propose that the most appropriate
      time for intervention implementation is earlier in adolescence, before the onset
      of risky behaviors.

PMID- 11576007
TI  - Is human immunodeficiency virus sexual risk prevention intervention effective?

PMID- 11576008
TI  - Empowering children and families with information technology.
AB  - Patient empowerment is the enhanced ability of patients to actively understand
      and influence their health status. Information is the key to patient empowerment.
      Without information, children and families cannot engage in meaningful
      discussions or make thoughtful decisions regarding medical care. Information
      sharing is a model for patient interaction with the health care system that may
      significantly improve the care of children and families. This article focuses on
      information technologies that utilize user-centered design principles and
      interactive capabilities to facilitate information sharing and to empower
      children and families. Examples include electronic pediatric personal medical
      records, customized health information systems, and interactive physician offices
      with electronic mail (e-mail) and telemedicine capabilities. Ideally, these
      systems would all be integrated. Successful implementation of new technologies
      will require thoughtful attention and balanced solutions to tensions between
      information sharing vs security, and curatorship vs censorship. Issues related to
      access and the digital divide must also be addressed. Acceptance and usability of
      new technologies is predicated on close collaboration among physicians,
      researchers in informatics, librarians, educators, and other professionals with
      expertise in the human-computer interface. Child and family empowerment will be
      both the driving force and ultimate outcome of information-sharing technologies.

PMID- 11576009
TI  - Assessing diagnostic accuracy and tympanocentesis skills in the management of
      otitis media.
AB  - BACKGROUND: The distinction between acute suppurative otitis media (AOM) and
      otitis media with effusion (OME) is important for antibiotic treatment decisions.
      Tympanocentesis may be useful in the diagnosis of AOM in selected patients.
      OBJECTIVES: To assess physician accuracy in diagnosing AOM and OME from physical
      examination findings and technical competence in performing tympanocentesis.
      DESIGN AND SUBJECTS: Five hundred fourteen pediatricians and 188
      otolaryngologists viewed 9 different videotaped pneumatic otoscopic examinations
      of tympanic membranes during a continuing medical education course. Diagnostic
      differentiation of AOM, OME, and a normal tympanic membrane was ascertained. An
      infant mannequin model was used to assess the technical proficiency of performing
      tympanocentesis on artificial tympanic membranes. RESULTS: Overall, the average
      correct diagnosis by pediatricians was 50% (range, 25%-73%) and by
      otolaryngologists was 73% (range, 48%-88%). Pediatricians and otolaryngologists
      correctly recognized the absence of normality 89% to 100% and 93% to 100% of the
      time, respectively, but overdiagnosed AOM in 7% to 53% (mean, 27%) and in 3% to
      23% (mean, 10%) of examinations. Performance of tympanocentesis was optimally
      performed by 89% of otolaryngologists and by 83% of pediatricians. CONCLUSIONS:
      The use of video-presented examinations to assess diagnostic ability suggests
      that AOM and OME may be misdiagnosed often. Interactive continuing medical
      education courses with simulation technology may enhance skills and improve
      diagnostic accuracy and treatment paradigms.

PMID- 11576010
TI  - Are perceived neighborhood hazards a barrier to physical activity in children?
AB  - BACKGROUND: We hypothesized that children's perceptions of more neighborhood
      hazards would be associated with less physical activity, less aerobic fitness,
      and a higher body mass index. OBJECTIVE: To examine the association between a
      hazardous neighborhood context and physical activity in children. METHODS: Fourth
      grade students (n = 796) of diverse ethnic and economic backgrounds completed
      measures of neighborhood hazards, self-reported physical activity, physical
      fitness, height, and weight. Parents (n = 518) completed telephone interviews and
      provided data on their education level and occupation. RESULTS: As expected,
      children from families of lower socioeconomic status perceived significantly more
      neighborhood hazards. Contrary to our hypothesis, the perception of more hazards
      was significantly associated with more reported physical activity. This finding
      was not explained by school heterogeneity, alteration of the hazards measure, or
      differences in socioeconomic status. CONCLUSION: To further examine the
      relationship between neighborhood hazards and physical activity, we suggest that
      future studies include assessments of sedentary behavior, parental fear of
      violence, parental regulation of children's leisure activities, and cost and
      quality of available play areas and organized sports.

PMID- 11576011
TI  - Improved documentation of retinal hemorrhages using a wide-field digital
      ophthalmic camera in patients who experienced abusive head trauma.
AB  - OBJECTIVE: To describe the clinical use of a wide-field digital ophthalmic camera
      (RetCam 120; Massie Research Laboratories, Inc, Dublin, Calif) for the
      documentation of retinal hemorrhages in patients who experienced abusive head
      trauma. DESIGN: Case series. SETTING: Pediatric intensive care unit at a tertiary
      care center. PARTICIPANTS: Children with suspected abusive head trauma. RESULTS:
      Eight children were studied during a 9-month period. The median age of the
      children was 2.25 months (range, 0.8-18.0 months). There were 4 male and 4 female
      patients. All patients had intracranial bleeding, documented by computed axial
      tomographic scans of the head. Of the 8 patients, 6 had bilateral retinal
      hemorrhages. All patients underwent a formal examination by a pediatric
      ophthalmologist (R.S. and others) using a wide-field digital ophthalmic camera.
      Three children died. CONCLUSIONS: The wide-field digital ophthalmic camera
      allowed good visualization and produced high-quality photographic images,
      resulting in instant bedside documentation of retinal pathological features. The
      wide-field digital ophthalmic camera provides a new tool for the evaluation and
      precise documentation of retinal hemorrhages in suspected and confirmed cases of
      abusive head trauma.

PMID- 11576012
TI  - Prevalence of mental disorders in children living in Alberta, Canada, as
      determined from physician billing data.
AB  - BACKGROUND: The prevalence of mental disorders is often assessed using survey
      techniques. Although providing good estimates of prevalence, these techniques are
      time-consuming and expensive. OBJECTIVE: To estimate the prevalence of mental
      disorders among children aged 0 to 17 years living in Alberta, Canada, using
      health care administrative data. DESIGN: This was a cross-sectional study.
      International Classification of Diseases, Ninth Revision, Clinical Modification
      chapter 5 diagnostic codes from physician billing data were used. Codes were
      grouped into 10 categories. Prevalence rates for each category were calculated,
      stratified by age, sex, and premium subsidy status (a proxy for socioeconomic
      status). The age pattern, times of greatest risk, and the effect of sex on type
      and prevalence of mental disorder were estimated. SETTING: All fee-for-service
      health care venues in Alberta between April 1, 1995, and March 31, 1996,
      providing services to children registered with the Alberta Health Care Insurance
      Commission on March 31, 1996. RESULTS: Prevalence of mental disorders varied by
      disorder category, age, sex, and premium subsidy status. For boys, maximum
      prevalence of 9.5% occurred at age 10 years; for girls, maximum prevalence of
      12.0% occurred at age 17 years. Mental disorders were most common in young boys
      and adolescent girls and among children receiving welfare. Distinct patterns of
      disorder were evident and comorbidity was common. CONCLUSIONS: Administrative
      data can be used to estimate the prevalence of mental disorders in a pediatric
      population. The estimates made are lower than those obtained by using surveys of
      similar populations, perhaps indicating the difference between treated and
      untreated prevalence. Strengths of this study are that the estimates reflect the
      entire population, are more easily and obtained at less cost, and are useful for
      the planning of mental health services.

PMID- 11576013
TI  - Low family income and food insufficiency in relation to overweight in US
      children: is there a paradox?
AB  - OBJECTIVES: To investigate associations between family income, food
      insufficiency, and being overweight in US children aged 2 to 7 and 8 to 16 years,
      to discuss mechanisms that may explain these associations, and to propose design
      and data requirements for further research that could effectively examine this
      issue. METHODS: Data from the Third National Health and Nutrition Examination
      Survey were analyzed. Children were classified as food insufficient if the family
      respondents reported that their family sometimes or often did not get enough food
      to eat. The prevalence of overweight was compared by family income category and
      food sufficiency status within age-, sex-, and race-ethnic-specific groups. Odds
      ratios for food insufficiency are reported, adjusted for family income and other
      potential confounding factors. RESULTS: Among older non-Hispanic white children,
      children in families with low income were significantly more likely to be
      overweight than children in families with high income. There were no significant
      differences by family income for younger non-Hispanic white children, non
      Hispanic black children, or Mexican American children. After adjusting for
      confounding variables, there were no differences in overweight by food
      sufficiency status, except that younger food-insufficient girls were less likely
      to be overweight, and non-Hispanic white older food-insufficient girls were more
      likely to be overweight than food-sufficient girls (P<.10). CONCLUSION: Further
      research to evaluate whether food insecurity causes overweight in American
      children requires longitudinal quantitative and in-depth qualitative methods.

PMID- 11576014
TI  - Picture of the month. Endogenous endophthalmitis.

PMID- 11576015
TI  - Radiological case of the month. Thoracic actinomyces.

PMID- 11576016
TI  - Pathological case of the month. Tuberculosis pleural effusion.

PMID- 11576017
TI  - Is public health ready for genetics? An unanswered question.

PMID- 11576019
TI  - Piracetam therapy for Down syndrome: a rush to judgment?

PMID- 11576020
TI  - Piracetam study: poorly designed and misinterpreted.

PMID- 11576022
TI  - Why ethnicity and race are so important in child health services research today.

PMID- 11576026
TI  - Cortical serotonin transporter density and verbal memory in individuals who
      stopped using 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"): preliminary
      findings.
AB  - BACKGROUND: Although the popular drug 3,4-methylenedioxymethamphetamine (MDMA or
      "ecstasy") has been shown to damage brain serotonin (5-HT) neurons in animals,
      the fate and functional consequences of 5-HT neurons after MDMA injury are not
      known in humans. We investigated the long-term effects of MDMA use on cortical 5
      HT neurons in humans and memory function, because brain 5-HT has been implicated
      in memory function. METHODS: Twenty-two recent MDMA users, 16 ex-MDMA users who
      had stopped using MDMA for more than 1 year, and 13 control subjects. The effects
      of MDMA use on cortical 5-HT neurons was studied by means of single-photon
      emission computed tomography with iodine 123-labeled 2beta-carbomethoxy-3beta-(4
      iodophenyl) tropane ([(123)I]beta-CIT) by quantification of brain 5-HT
      transporter densities. Verbal memory performance was assessed with the Rey
      Auditory Verbal Learning Test. RESULTS: Mean cortical [(123)I]beta-CIT-labeled 5
      HT transporter density was significantly lower in recent MDMA users than in
      controls (1.17 vs. 1.28 [-9%]) but not in ex-MDMA users (1.24 vs. 1.28 [-3%]).
      Recent and ex-MDMA users recalled significantly fewer words than did controls on
      the immediate recall (47.0 and 48.0 vs 60.0, respectively; P =.001) as well as
      the delayed recall (9.8 and 10.1 vs. 13.1, respectively; P =.003). Greater use of
      MDMA was associated with greater impairment in immediate verbal memory. However,
      memory performance was not associated with [(123)I]beta-CIT binding to cortical 5
      HT transporters or duration of abstinence from MDMA. CONCLUSION: The present
      study suggests that, while the neurotoxic effects of MDMA on 5-HT neurons in the
      human cortex may be reversible, the effects of MDMA on memory function may be
      long-lasting.

PMID- 11576027
TI  - "Ecstasy" and serotonin neurotoxicity: new findings raise more questions.

PMID- 11576028
TI  - Neuropsychological performance in long-term cannabis users.
AB  - BACKGROUND: Although cannabis is the most widely used illicit drug in the United
      States, its long-term cognitive effects remain inadequately studied. METHODS: We
      recruited individuals aged 30 to 55 years in 3 groups: (1) 63 current heavy users
      who had smoked cannabis at least 5000 times in their lives and who were smoking
      daily at study entry; (2) 45 former heavy users who had also smoked at least 5000
      times but fewer than 12 times in the last 3 months; and (3) 72 control subjects
      who had smoked no more than 50 times in their lives. Subjects underwent a 28-day
      washout from cannabis use, monitored by observed urine samples. On days 0, 1, 7,
      and 28, we administered a neuropsychological test battery to assess general
      intellectual function, abstraction ability, sustained attention, verbal fluency,
      and ability to learn and recall new verbal and visuospatial information. Test
      results were analyzed by repeated-measures regression analysis, adjusting for
      potentially confounding variables. RESULTS: At days 0, 1, and 7, current heavy
      users scored significantly below control subjects on recall of word lists, and
      this deficit was associated with users' urinary 11-nor-9-carboxy-Delta9
      tetrahydrocannabinol concentrations at study entry. By day 28, however, there
      were virtually no significant differences among the groups on any of the test
      results, and no significant associations between cumulative lifetime cannabis use
      and test scores. CONCLUSION: Some cognitive deficits appear detectable at least 7
      days after heavy cannabis use but appear reversible and related to recent
      cannabis exposure rather than irreversible and related to cumulative lifetime
      use.

PMID- 11576029
TI  - Marijuana abstinence effects in marijuana smokers maintained in their home
      environment.
AB  - BACKGROUND: Although withdrawal symptoms are commonly reported by persons seeking
      treatment for marijuana dependence, the validity and clinical significance of a
      marijuana withdrawal syndrome has not been established. This controlled
      outpatient study examined the reliability and specificity of the abstinence
      effects that occur when daily marijuana users abruptly stop smoking marijuana.
      METHODS: Twelve daily marijuana smokers were assessed on 16 consecutive days
      during which they smoked marijuana as usual (days 1-5), abstained from smoking
      marijuana (days 6-8), returned to smoking marijuana (days 9-13), and again
      abstained from smoking marijuana (days 14-16). RESULTS: An overall measure of
      withdrawal discomfort increased significantly during the abstinence phases and
      returned to baseline when marijuana smoking resumed. Craving for marijuana,
      decreased appetite, sleep difficulty, and weight loss reliably changed across the
      smoking and abstinence phases. Aggression, anger, irritability, restlessness, and
      strange dreams increased significantly during one abstinence phase, but not the
      other. Collateral observers confirmed participant reports of these symptoms.
      CONCLUSIONS: This study validated several specific effects of marijuana
      abstinence in heavy marijuana users, and showed they were reliable and clinically
      significant. These withdrawal effects appear similar in type and magnitude to
      those observed in studies of nicotine withdrawal.

PMID- 11576030
TI  - Magnetic resonance imaging correlates of depression after ischemic stroke.
AB  - BACKGROUND: Depression affects up to 40% of patients with ischemic stroke. The
      relationship between site and size of brain infarcts and poststroke depression is
      still not well characterized. Further possible contribution and interaction of
      white matter lesions and brain atrophy has not been studied previously. We
      conducted a magnetic resonance image-based study of the radiologic correlates of
      depression in a large, well-defined series of patients with ischemic stroke.
      METHODS: Modified DSM-III-R and DSM-IV criteria were used to diagnose depressive
      disorders during a comprehensive psychiatric evaluation in 275 of 486 consecutive
      patients aged 55 to 85 years 3 to 4 months after ischemic stroke. A standardized
      magnetic resonance imaging protocol detailed side, site, type, and extent of
      brain infarcts and extent of white matter lesions and brain atrophy. RESULTS:
      Depressive disorders were diagnosed in 109 patients (40%). Patients with
      depression had a higher number and larger volume of infarcts affecting the
      prefrontosubcortical circuits, especially the caudate, pallidum, and genu of
      internal capsule, with left-sided predominance. Extent of white matter lesions
      and atrophy did not differ in patients with and without depression. Independent
      correlates of poststroke depression in a logistic regression model were mean
      frequency of infarcts in the genu of internal capsule on the left side (odds
      ratio [OR], 3.2; 95% confidence interval [CI], 1.0-10.1), mean frequency of
      infarcts in the pallidum of any side (OR, 1.6; 95% CI, 1.1-2.3), and mean volume
      of infarcts in the right occipital lobe (OR, 0.98; 95% CI, 0.96-0.99).
      CONCLUSION: Lesions affecting the prefrontosubcortical circuits, especially on
      the left side, are correlates of depression after ischemic stroke.

PMID- 11576031
TI  - Two-year effects of quality improvement programs on medication management for
      depression.
AB  - BACKGROUND: Significant underuse of evidence-based treatments for depression
      persists in primary care. We examined the effects of 2 primary care-based quality
      improvement (QI) programs on medication management for depression. METHODS: A
      total of 1356 patients with depressive symptoms (60% with depressive disorders
      and 40% with subthreshold depression) from 46 primary care practices in 6
      nonacademic managed care organizations were enrolled in a randomized controlled
      trial of QI for depression. Clinics were randomized to usual care or to 1 of 2 QI
      programs that involved training of local experts who worked with patients'
      regular primary care providers (physicians and nurse practitioners) to improve
      care for depression. In the QI-medications program, depression nurse specialists
      provided patient education and assessment and followed up patients taking
      antidepressants for up to 12 months. In the QI-therapy program, depression nurse
      specialists provided patient education, assessment, and referral to study-trained
      psychotherapists. RESULTS: Participants enrolled in both QI programs had
      significantly higher rates of antidepressant use than those in the usual care
      group during the initial 6 months of the study (52% in the QI-medications group,
      40% in the QI-therapy group, and 33% in the usual care group). Patients in the QI
      medications group had higher rates of antidepressant use and a reduction in long
      term use of minor tranquilizers for up to 2 years, compared with patients in the
      QI-therapy or usual care group. CONCLUSIONS: Quality improvement programs for
      depression in which mental health specialists collaborate with primary care
      providers can substantially increase rates of antidepressant treatment. Active
      follow-up by a depression nurse specialist in the QI-medications program was
      associated with longer-term increases in antidepressant use than in the QI model
      without such follow-up.

PMID- 11576032
TI  - Prevalence of psychiatric disorders among persons convicted of driving while
      impaired.
AB  - BACKGROUND: Large numbers of convicted drunk drivers are entering alcohol
      treatment programs, yet little information is available about their need for
      psychiatric treatment. This study of convicted drunk drivers estimates lifetime
      and 12-month prevalence of DSM-III-R psychiatric disorders (alcohol and drug
      abuse and dependence, major depressive disorder, dysthymic disorder, generalized
      anxiety disorder, posttraumatic stress disorder, and antisocial personality
      disorder) and compares rates with estimates from a US population-based survey.
      METHODS: Six hundred twelve women and 493 men, aged 23 to 54 years, convicted of
      driving while impaired, who had been referred to a screening program in
      Bernalillo County, New Mexico, were located and interviewed using the Diagnostic
      Interview Schedule between January 25, 1994, and June 30, 1997. Psychiatric
      diagnoses were compared with findings from the National Comorbidity Survey for
      the western region of the United States, conducted between September 14, 1990,
      and February 6, 1992. RESULTS: Eighty-five percent of female and 91% of male
      offenders reported a lifetime alcohol-use disorder, compared with 22% and 44%,
      respectively, in the National Comorbidity Survey sample. Thirty-two percent of
      female and 38% of male offenders had a drug-use disorder, compared with 16% and
      21%, respectively, in the National Comorbidity Survey sample. For offenders with
      alcohol-use disorders, 50% of women and 33% of men had at least 1 additional
      psychiatric disorder other than drug abuse or dependence, mainly posttraumatic
      stress disorder or major depression. CONCLUSION: Drunk-driving offenders need
      assessment and treatment services not only for alcohol problems but also for drug
      use and the other psychiatric disorders that commonly accompany alcohol-related
      problems.

PMID- 11576033
TI  - More reasons to buckle your seat belt.

PMID- 11576034
TI  - Aberrant tyrosine transport across the cell membrane in patients with
      schizophrenia.
AB  - BACKGROUND: There is evidence that patients with schizophrenia exhibit
      abnormalities, not only in the brain but also in peripheral organs. An abnormal
      cell membrane composition has been suggested to be a common denominator,
      supported by findings of alterations in membrane phospholipid levels. In a
      previous study, the transport of amino acids across the plasma membrane was
      investigated with fibroblasts from patients with schizophrenia and controls. An
      isolated decrease in the maximal transport capacity (V(max)) of tyrosine was
      observed in the cells from patients. In this context, tyrosine transport across
      the fibroblast membrane was investigated in patients with schizophrenia and
      healthy control subjects. METHODS: Skin fibroblasts were obtained from 36
      patients with schizophrenia (15 first episode and 21 chronic) and 10 healthy
      controls. Tyrosine transport across the cell membrane was studied in cultivated
      fibroblasts. The V(max) and the affinity of the tyrosine binding sites (K(m))
      were determined. RESULTS: Significantly lower V(max) (F(1,41) = 12.80; P =.001;
      effect size = 1.36) and K(m) (F(1,41) = 24.85; P<.001; effect size = 1.00) were
      observed in fibroblasts from the patients. The findings were present in both
      neuroleptic-naive patients with their first episode and patients with chronic
      schizophrenia. CONCLUSIONS: The lower V(max) and K(m) are compatible with a cell
      membrane disturbance and support the view of schizophrenia as a systemic
      disorder. The decreased V(max) and K(m) observed in cells from schizophrenic
      patients probably reflect a genetic trait, as the changes were transmitted
      through several cell generations of cultured fibroblast.

PMID- 11576035
TI  - Association between nonpsychotic psychiatric diagnoses in adolescent males and
      subsequent onset of schizophrenia.
AB  - BACKGROUND: Nonpsychotic psychiatric symptoms may occasionally herald the later
      development of schizophrenia. This study followed a population-based cohort of
      adolescents with nonpsychotic, non-major affective psychiatric disorders to
      ascertain future hospitalization for schizophrenia. METHODS: Results of the
      medical and mental health assessments on 124 24416- to 17-year-old males screened
      by the Israeli draft board were cross-linked with the National Psychiatric
      Hospitalization case registry, which contains data on all psychiatric
      hospitalizations in the country, during a 4- to 8-year-long follow-up through age
      25 years. In the cohort, 9365 adolescents were assigned a nonpsychotic, non-major
      affective diagnosis by the draft board. RESULTS: After excluding 167 adolescents
      who were hospitalized before or up to 1 year after the draft board assessment,
      1.03% of the adolescents assigned a nonpsychotic, non-major affective psychiatric
      diagnosis, compared with only 0.23% of the adolescents without any psychiatric
      diagnosis, were later hospitalized for schizophrenia. Of the patients with
      schizophrenia, 26.8%, compared with only 7.4% in the general population, had been
      assigned a nonpsychotic, non-major affective psychiatric diagnosis in adolescence
      (overall odds ratio [OR], 4.5; 95% confidence interval [CI], 3.6-5.6), ranging
      from OR, 21.5 (95% CI, 12.6-36.6) for schizophrenia spectrum personality
      disorders to OR, 3.6 (95% CI, 2.1-6.2) for neurosis. CONCLUSION: These results
      reflect the relatively common finding of impaired functioning in patients later
      hospitalized for schizophrenia and the relatively low power of these disorders in
      predicting schizophrenia.

PMID- 11576036
TI  - Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month
      randomized and double-blind comparison.
AB  - BACKGROUND: Despite the demonstrated efficacy of clozapine in severely refractory
      schizophrenia, questions remain regarding its efficacy for primary negative
      symptoms, comparison with a moderate dose of a first-generation antipsychotic,
      and adverse effects during a longer-term trial. This study examined its efficacy
      in partially responsive, community-based patients, compared clozapine with
      moderate-dose haloperidol, and extended treatment to 6 months. METHODS:
      Randomized, double-blind, 29-week trial comparing clozapine (n = 37) with
      haloperidol (n = 34). Subjects with schizophrenia who were being treated in
      community settings at 3 collaborating clinical facilities were enrolled. RESULTS:
      Subjects treated with haloperidol were significantly more likely to discontinue
      treatment for lack of efficacy (51%) than were those treated with clozapine
      (12%). A higher proportion of clozapine-treated subjects met an a priori
      criterion of improvement (57%) compared with haloperidol-treated subjects (25%).
      Significantly greater improvement was seen in symptoms of psychosis, hostile
      suspiciousness, anxiety-depression, thought disturbance, and total score measured
      on the Brief Psychiatric Rating Scale. No differences were detected in negative
      symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment
      of Negative Symptoms. Subjects treated with clozapine experienced more excess
      salivation, dizziness, and sweating and less dry mouth and decreased appetite
      than those treated with haloperidol. CONCLUSIONS: Compared with a first
      generation antipsychotic given in a moderate dose, clozapine offers substantial
      clinical benefits to treatment-refractory subjects who can be treated in the
      community. Advantages are seen in a broad range of symptoms but do not extend to
      negative symptoms.

PMID- 11576037
TI  - Lithium: an orphan drug.

PMID- 11576038
TI  - Repetitive transcranial magnetic stimulation at the frontopolar cortex reduces
      skin conductance but not heart rate: reduced gray matter excitability in
      orbitofrontal regions.

PMID- 11576040
TI  - Chronic pain after sternotomy.

PMID- 11576041
TI  - Pharmacokinetics and drug dosing adjustments during continuous venovenous
      hemofiltration or hemodiafiltration in critically ill patients.
AB  - Continuous renal replacement therapy (CRRT) in critically ill patients with renal
      failure may significantly increase drug clearance, requiring drug dosing
      adjustments. Drugs significantly eliminated by the kidney often undergo
      substantial removal during CRRT, and a supplemental dose corresponding to the
      amount of drug removed by CRRT should be administered. Clearance by CRRT can
      either be measured or estimated. The high-flux membranes used in CRRT make no
      filtration barrier to most drugs, and the filtrate concentration can be estimated
      by the unbound fraction of the drug in plasma. When adding dialysis to
      filtration, this approach overestimates drug clearance, and a correcting factor
      should be used. A method for estimating drug clearance as a function of
      creatinine clearance is also suggested, but it has the same limitations in
      overestimating drug clearance when dialysis is combined with filtration. For non
      toxic drugs, doses can safely be increased 30% above actual estimates to ensure
      adequate dosing. For drugs with a narrow therapeutical margin, monitoring plasma
      concentrations are mandatory. When appropriate, the use of a readily available
      reference for drug dosing is recommended.

PMID- 11576042
TI  - Chronic post-sternotomy pain.
AB  - BACKGROUND: Chronic postoperative pain is a well-recognised problem. The
      incidence of severe incapacitating pain is about 3-5% after various types of
      surgery such as thoracotomy, repair of inguinal hernias and mastectomy.
      Sternotomy causes considerable postoperative pain and patients with chronic post
      sternotomy pain are often referred to pain clinics. Epidemiological studies on
      chronic post-sternotomy pain are scarce, however. The aim of this paper was to
      study the incidence and possible risk factors of chronic pain following
      sternotomy operations performed for coronary bypass grafting or thymectomy.
      METHODS: Two groups of patients were studied for persistent pain following
      sternotomy operations. A questionnaire was sent in January 1997 to 71 patients
      with myasthenia gravis (MG) who had undergone a thymectomy during 1985-1996 and
      720 patients who had had coronary bypass grafting (CABG) in 1994 were interviewed
      by letter. The patients were asked about the presence of pain and other symptoms
      in the chest, shoulders, arms or legs that they thought were connected to
      surgery. They were also asked about the quality of the pain and its evolvement
      with time. The patients' records were checked for details about surgery,
      anaesthesia and the state of the coronary disease. RESULTS: The response rate was
      87%. The interval between the interview and surgery varied from 6 months to 12
      years in the MG group and it was 2-3 years in the CABG group. In the MG group,
      27% of the patients reported chronic post-sternotomy pain, which was moderate to
      severe in 48% of the patients. In the CABG group, 28% of the patients still had
      post-sternotomy pain, which was moderate to severe in 38% of patients. Of the
      patients who had post-sternotomy pain, one-third reported sleep disturbances due
      to the pain. CONCLUSION: Chronic post-sternotomy pain is an important
      complication that may have a significant impact on the patient's everyday life.
      Future studies will show whether minimising complications, improving
      postoperative care and starting early adequate pain management will reduce the
      incidence of this problem.

PMID- 11576043
TI  - The incidence of chronic post-sternotomy pain after cardiac surgery--a
      prospective study.
AB  - BACKGROUND: Post-sternotomy pain is sometimes a sequela of cardiac surgery. The
      incidence, characteristics and clinical course of post-sternotomy pain are not
      well known. The aim of our study was to determine the incidence of chronic post
      sternotomy pain in patients undergoing sternotomy for cardiac surgery in general
      and according to the specific surgical procedure. METHOD: In a prospective
      manner, a group of 349 consecutive patients were evaluated for chronic post
      sternotomy pain one year after surgery. The patients were asked in a postal
      questionnaire to describe and score any persistent pain following the surgical
      procedure. The patients were classified into 3 sub-groups according to surgical
      procedure. The first group consisted of patients operated for coronary artery by
      pass grafting (CABG) including internal thoracic artery grafting (ITAG). The
      second group included patients operated with CABG without ITAG and the third
      group of patients with valve replacement without CABG. RESULT: A total of 318
      patients (91%) answered the questionnaire of whom 90 (28%) reported chest
      discomfort different from what they experienced before surgery. The scoring on
      the visual analogue scale (VAS, 0-100 mm) showed that 41 patients (13%) reported
      maximum pain intensity > or =30 mm (moderate pain), and 14 of these patients (4%)
      scored > or =54 mm (severe pain). There was no statistically significant
      difference in pain incidence and pain intensity when comparing the patients
      subjected to different surgical procedures. CONCLUSIONS: This prospective study
      shows that the overall incidence of non-cardiac pain after sternotomy for cardiac
      surgery is high (28%). Most patients experience a modest pain intensity but some
      (1%) report severe pain, never being lower than 54 mm on VAS. The study also
      indicates that the incidence of pain after sternotomy is not only associated with
      harvest of the ITA and additional aetiological factors must be sought.

PMID- 11576044
TI  - Evidence that spinal segmental nitric oxide mediates tachyphylaxis to peripheral
      local anesthetic nerve block.
AB  - BACKGROUND: Tachyphylaxis to sciatic nerve blockade in rats correlates with
      hyperalgesia. Spinal inhibition of nitric oxide synthase with N(G)nitro-L
      arginine methyl ester (L-NAME) has been shown to prevent hyperalgesia. Given
      systemically, L-NAME also prevents tachyphylaxis. The action of L-NAME in
      preventing tachyphylaxis therefore may be mediated at spinal sites. We compared
      systemic versus intrathecal potency of L-NAME in modulating tachyphylaxis to
      sciatic nerve block. METHODS: Rats were prepared with intrathecal catheters.
      Three sequential sciatic nerve blocks were placed. Duration of block of thermal
      nocifensive, proprioceptive and motor responses was recorded. We compared spinal
      versus systemic dose-response to L-NAME, and examined effects of intrathecal
      arginine on tachyphylaxis. An additional group of rats underwent testing after
      T10 spinal cord transection. In these rats duration of sciatic nerve block was
      assessed by determining the heat-induced flexion withdrawal reflex. RESULTS: L
      NAME was 25-fold more potent in preventing tachyphylaxis given intrathecally than
      intraperitoneally. Intrathecal arginine augmented tachyphylaxis. Spinalized rats
      exhibited tachyphylaxis to sciatic block. CONCLUSION: The increased potency of
      intrathecal versus systemic L-NAME suggests a spinal site of action in inhibiting
      tachyphylaxis. Descending pathways are not necessary for the development of
      tachyphylaxis since it occurs even after T10 spinal cord transection. Thus
      tachyphylaxis, like hyperalgesia, is mediated at least in part by a spinal site
      of action.

PMID- 11576045
TI  - Effect of naloxone on primary and secondary hyperalgesia induced by the human
      burn injury model.
AB  - BACKGROUND: Opioid antagonists may change the responses in models of experimental
      hyperalgesia. This indicates a possible involvement of the endogenous opioid
      system in these models. The aim of the present study was to evaluate whether
      activation of the endogenous opioid system could be demonstrated in the human
      burn injury model of cutaneous hyperalgesia, using an intravenous challenge with
      the non-selective opioid antagonist naloxone. METHODS: We studied 25 healthy male
      volunteers aged 20-31 yrs in a randomised, double-blind, triple crossover design.
      A 25x50 mm rectangular burn injury was produced on the calf on 3 separate days,
      at least 1 week apart. Subjects received an intravenous bolus dose of naloxone
      0.4 mg, 10 mg or placebo 3 h after induction of the burn injury. RESULTS: Primary
      and secondary hyperalgesia was induced by the burn injury. Naloxone did not
      affect any of the measured variables: heat pain detection threshold in non
      injured or injured tissue, pain produced by short or prolonged noxious heat in
      non-injured or injured tissue, secondary hyperalgesia elicited by pin prick or
      stroke, or pain produced by short or prolonged noxious mechanical stimulation in
      non-injured tissue. No significant adverse effects of naloxone were encountered.
      CONCLUSIONS: Activation of an endogenous opioid response following induction of
      hyperalgesia in human volunteers by a burn injury could not be demonstrated with
      an intravenous naloxone challenge. These findings suggest that the endogenous
      opioid response is not a confounding factor in this model.

PMID- 11576046
TI  - Comparison of lignocaine 2% with adrenaline, bupivacaine 0.5% with or without
      hyaluronidase and a mixture of bupivacaine, lignocaine and hyaluronidase for
      peribulbar block analgesia.
AB  - PURPOSE: Each of the freely available local analgesic agents may be used, alone
      or in combination, with or without hyaluronidase, epinephrine and sodium
      bicarbonate for peribulbar block analgesia (PBA). A prospective audit of four
      solutions was undertaken to rationalize choice of local analgesic agent for PBA.
      METHODS: A randomized, prospective study on 200 middle-aged to elderly patients
      undergoing cataract extraction was undertaken to compare the efficacy of: (1)
      bupivacaine 0.5% (bup 0.5% plain); (2) bupivacaine 0.5% plus hyaluronidase 100
      i.u. ml-1 (bup 0.5% hyalase); (3) lidocaine 2% plus epinephrine 1:200 000 (lido
      2% epi); or (4) a mixture of lidocaine 2% and bupivacaine 0.5% (2:3 volume per
      volume mix) containing hyaluronidase 25 i.u. ml-1 (lido/bup/hyalase). A
      standardized deep peribulbar block technique, akinesia scoring system (each 5
      minx4), and supplemental protocol was followed. Onset of block and
      supplementation rates to achieve akinesia were recorded by a blinded observer;
      the requirement for augmentation with topical oxybuprocaine or subconjunctival
      lidocaine during surgery and the time from first PBA injection to the completion
      of surgery (the duration of surgical access) were also recorded. RESULTS: Groups
      (N=50) were comparable. Akinesia scores were similar after each agent at 5 min,
      better with lido 2% epi compared with bup 0.5% plain at 10 min (P<0.05), and
      better with bup 0.5% hyalase, lido 2% epi, and lido/bup/hyalase, than with bup
      0.5% plain at 15 min (P<0.01, <0.01, <0.05, respectively) and at 20 min (P<0.05,
      <0.05, <0.025, respectively). The supplementation rate at 5 min was least with
      lido 2% epi, greater with bup 0.5% plain (P<0.01) and bup 0.5% hyalase (P<0.0005)
      and greatest with lido/bup/hyalase (P<0.0005), but similar in each group at 10,
      15 and 20 min. Overall, those given lido 2% epi required the least number of
      supplemental injections to achieve globe akinesia. Mean supplemental injectate
      volumes, augmentation rates during surgery and the durations of surgical access
      provided by each agent were similar. CONCLUSION: All four agents provided
      adequate analgesia during cataract extraction lasting approximately 95-100 min
      after PBA injection. Lido 2% epi demonstrated most rapid onset and required least
      number of injections to establish block. A hyaluronidase effect was evident only
      after 15 min in the bup 0.5% hyalase and lido/bup/hyalase groups. Bup 0.5% plain
      was overall the least satisfactory, and the greatest supplementation rate
      occurred with lido/bup/hyalase, suggesting that either lido 2% epi or bup 0.5%
      hyalase are the most suitable of the agents tested for this type of surgery.

PMID- 11576047
TI  - A comparison of 0.5% ropivacaine and 1% mepivacaine for sciatic nerve block in
      the popliteal fossa.
AB  - BACKGROUND: The purpose of this study was to compare anesthetic efficacy and
      postoperative analgesia of 0.5% ropivacaine and 1% mepivacaine for sciatic nerve
      block in the popliteal fossa (popliteal block). METHODS: A prospective, double
      blind study was carried out in 58 adult patients scheduled for outpatient foot or
      ankle surgery. They were randomized to receive popliteal block with 40 ml of
      either 0.5% ropivacaine (group R) or 1% mepivacaine (group M). An atraumatic,
      Teflon-coated needle connected to a neurostimulator was used to make a single
      puncture using a posterior approach. The times to onset of sensory and motor
      block, and the need for intraoperative sedation were recorded. Before discharge,
      patients were asked to document the time to first analgesic use, time to return
      of full sensation in the foot, and their evaluation of the technique. RESULTS:
      Onset time (mean+/-standard deviation, 95% confidence interval) of both sensory
      block (6.5+/-5.1 min, 4.47-8.49, in group R and 6.2+/-3.7 min, 4.83-7.69, in
      group M) and motor block (6.6+/-4.4 min, 4.81-8.23, in group R and 7.9+/-4.1 min,
      6.29-9.53, in group M) was similar in both groups. Postoperative analgesia lasted
      longer in group R (15.2+/-5.1 h, 13.25-17.21) than in group M (5.7+/-1.8 h, 5.01
      6.41; P<0.001). Duration of sensory block was longer in group R (20.7+/-6.2 h,
      18.51-23.01) than in group M (6.5+/-1.7 h, 5.86-7.16; P<0.001). Acceptance of the
      anesthetic procedure was similar in both groups. CONCLUSION: In this study we
      demonstrated that both 0.5% ropivacaine and 1% mepivacaine for popliteal block
      produced rapid, effective and safe anesthesia but postoperative analgesia was
      more long-lasting with ropivacaine.

PMID- 11576048
TI  - Effects of remifentanil/propofol in comparison with isoflurane on dynamic
      cerebrovascular autoregulation in humans.
AB  - BACKGROUND: This study investigates the effects of remifentanil and propofol in
      comparison to isoflurane on dynamic cerebrovascular autoregulation in humans.
      METHODS: In 16 awake patients dynamic cerebrovascular autoregulation was measured
      using transcranial Doppler sonography (TCD). Thereafter patients were intubated,
      ventilated with O2/air (FiO2=0.33) and randomly assigned to one of the following
      anesthetic protocols: group 1 (n=8): 0.5 microg x kg(-1) x min(-1) remifentanil
      combined with a propofol-target plasma concentration of 1.5 microg x ml(-1) group
      2 (n=8): 1.8 % isoflurane (1.5 MAC). Following 20 min of equilibration the
      autoregulatory challenge was repeated. Arterial blood gases and body temperature
      were maintained constant over time. STATISTICS: Mann-Whitney U-test and Wilcoxon
      signed-rank test. RESULTS: Dynamic autoregulation was intact in all patients
      prior to induction of anesthesia expressed by an autoregulatory index (ARI) of
      5.4+/-1.21 (mean+/-SD, group 1) and 5.9+/-0.98 (mean+/-SD, group 2). With
      remifentanil/propofol anesthesia dynamic autoregulation was similar to the awake
      state (group 1: ARI=4.9+/-0.88). In contrast, autoregulatory response was delayed
      with 1.5 MAC isoflurane (group 2, ARI=2.1+/-0.92) (P<0.05). CONCLUSION: These
      data show that dynamic cerebrovascular autoregulation is maintained with
      remifentanil-based total intravenous anesthesia. This is consistent with the view
      that narcotics (and hypnotics) do not alter the physiologic cerebrovascular
      responses to changes in MAP. In contrast, 1.5 MAC isoflurane delays
      cerebrovascular autoregulation compared to the awake state.

PMID- 11576049
TI  - Intracerebral microdialysis and bedside biochemical analysis in patients with
      fatal traumatic brain lesions.
AB  - BACKGROUND: Microdialysis with bedside biochemical analysis was used to monitor
      cerebral biochemical alterations that precede and accompany increase in
      intracranial pressure (ICP), resulting in a complete cessation of cerebral blood
      flow. METHODS: Seven patients, who died due to an untreatable increase in ICP,
      were included. The patients originate from a large, consecutive series of
      severely head injured patients (n: 95) monitored with intracerebral microdialysis
      (perfusion rate 0.3 microl/min). One microdialysis catheter was inserted via a
      separate burr hole frontally to that used for the intraventricular catheter
      ("better" position) and one catheter was inserted into cerebral cortex
      surrounding an evacuated focal contusion or underlying an evacuated haematoma
      ("worse" position). Biochemical analyses of glucose, lactate, glycerol, urea,
      glutamate, and pyruvate were performed at the bedside. All samples were frozen
      for subsequent HPLC (high-performance liquid chromatography) analyses of amino
      acids and ions. RESULTS: Decreases in glucose and pyruvate and increases in
      lactate, glycerol, glutamate, and lactate/pyruvate (la/py) ratio characterized
      cerebral ischaemia. The measured markers give information regarding substrate
      availability (glucose), redox state of the tissue (la/py ratio), degradation of
      glycerophospholipids in cell membranes (glycerol), and extracellular
      concentration of excitatory amino acids (glutamate). In the "worse" position
      biochemical deterioration occurred before the increase in ICP. In the "better"
      position biochemical deterioration was usually observed after the increase in
      ICP. CONCLUSION: Changes of cerebral energy metabolism that accompany cerebral
      ischaemia follow a certain pattern and may be detected at the bedside by
      intracerebral microdialysis before the secondary damage causes an increase in
      ICP.

PMID- 11576050
TI  - Lung recruitment at birth does not improve lung function in immature lambs
      receiving surfactant.
AB  - BACKGROUND: In mature animals with surfactant deficiency induced by lung lavage,
      the therapeutic effect of exogenous surfactant is enhanced by a lung recruitment
      maneuver. We then tested whether a lung recruitment maneuver at birth immediately
      before surfactant treatment would improve lung function also in preterm lambs
      with surfactant deficiency due to immaturity. METHODS: Ten newborn lambs with a
      gestational age of 127 days were randomized to receive surfactant either before
      the first breath or immediately after a lung recruitment maneuver consisting of
      five sustained inflations of 8, 16 or 32 ml/kg. Functional residual capacity was
      measured by sulfur hexafluoride washout, and inspiratory capacity as well as
      maximal compliance were obtained from a static expiratory pressure-volume curve
      after the lungs had been inflated to 35 cm H2O. In addition, blood gases were
      obtained. Measurements were made at 15, 45, 175, 135, 170 and 230 min after
      birth. Post mortem histological examinations of the lungs were performed in a
      blinded fashion. RESULTS: The lung recruitment maneuvers did not improve
      oxygenation. Inspiratory capacity, static compliance and functional residual
      capacity at 4 h, as well as post mortem intrapulmonary air volume, had an inverse
      relation to the size of inflations given at birth. There was also a negative
      correlation between size of inflations at birth and response to surfactant
      therapy, as assessed by lung microscopy. CONCLUSION: Lung recruitment at birth
      does not improve the response to surfactant in immature lambs, but may instead
      have an adverse effect on lung function and morphology.

PMID- 11576051
TI  - Moderate hypothermia blunts the inflammatory response and reduces organ injury
      after acute haemorrhage.
AB  - BACKGROUND: Reduced body temperature is a common companion to trauma/haemorrhage.
      Several clinical studies have identified hypothermia as an independent risk
      variable predisposing to increased morbidity and mortality. At the same time it
      is known that most enzymatic reactions are downregulated at temperatures below 37
      degrees C. Theoretically this should restrain the inflammatory response and
      protect the host from remote organ injury. The study was performed to test this
      hypothesis. METHODS: Twenty-six male Sprague Dawley rats were used for the
      experiments. Volume controlled haemorrhagic shock was induced by withdrawal of
      2.5 ml blood/100 g body weight over 10 min. Half of the animals (n=13) were then
      cooled to 32.5-33 degrees C, the other half (n=13) were kept normothermic (37.5+/
      0.5 degrees C). Seventy-five minutes after initiation of bleeding, two-thirds of
      the blood was retransfused. Thereafter the rats were observed for 2 h. Key
      substances of systemic inflammation were determined (plasma values of TNF-alpha,
      IL-6, IL-10, and corticosterone; reactive oxygen species in peritoneal
      phagocytes), plasma markers of organ function and integrity (AST, ALT, alphaGST,
      creatinine, urea), and survival. RESULTS: Hypothermia reduced the release of IL-6
      (P<0.01). The reductions of plasma levels of TNFalpha (P=0.07) and IL-10 (P=0.09)
      were less clear-cut. The release of reactive oxygen species diminished (P<0.01).
      Organ injury was ameliorated, as reflected by decreased levels of AST (P<0.01),
      alphaGST (P<0.01), and creatinine (P<0.01). Both groups experienced an almost
      identical increase of plasma corticosterone. None of the hypothermic rats died,
      compared to two normothermic. CONCLUSION: Moderate hypothermia had an organ
      protective effect in this model of controlled haemorrhagic shock. This coincided
      with a significant reduction of the proximal cytokine IL-6 and reactive oxygen
      species, which conceivably influenced the outcome.

PMID- 11576052
TI  - Spontaneous movements, local reactions and pain on injection of rocuronium. A
      comparison between female and male patients.
AB  - BACKGROUND: We investigated the incidence of withdrawal, local reactions and pain
      on injection of rocuronium in 120 adult ASA I-II patients undergoing general
      anaesthesia (group A: 60 male patients, group B: 60 female patients). METHODS:
      After induction of anaesthesia with propofol and remifentanil, rocuronium 0.6 mg
      kg(-1) was injected in a separate intravenous cannula on the opposite arm. The
      patient's response to the injection of rocuronium was graded using a four-point
      scale. The appearance of local signs (i.e. erythema, venous sequelae) on the arm
      where rocuronium had been injected was recorded at the end of the injection as
      well as 1 h and 24 h after recovery from anaesthesia. Moreover, patients were
      asked 24 h after recovery from anaesthesia whether they had recall of pain or
      movements in this arm during induction of anaesthesia. RESULTS: In 26 of the 120
      patients (22%) included, withdrawal reactions after injection of rocuronium were
      observed. Of these 26 patients, 16 (13%) had severe movements. The overall
      incidence of withdrawal reactions after rocuronium as well as the incidence of
      severe reactions was significantly higher in female patients compared to male
      patients (overall incidence: 18 females (30%) vs. 8 males (13%), P<0.05; severe
      reaction: 13 females (22%) vs. 3 males (5%), P<0.05). No local reactions were
      observed and no patient remembered any pain or movements during induction of
      anaesthesia. CONCLUSION: The incidence and the degree of withdrawal reactions in
      response to the injection of rocuronium were significantly higher in women than
      in men. This was not associated with adverse clinical consequences for the
      patient's outcome.

PMID- 11576053
TI  - Dose-response relationship of propofol on mid-latency auditory evoked potentials
      (MLAEP) in cardiac surgery.
AB  - BACKGROUND: Propofol-sufentanil anaesthesia has become popular during cardiac
      surgery for its titrability and short recovery time. Avoidance of awareness is a
      major goal during cardiac surgery. We therefore investigated the dose-response
      relationship of propofol and cortical responses (mid-latency auditory evoked
      potentials, MLAEP). METHODS: One hundred patients undergoing cardiac surgery were
      investigated. Basic anaesthesia was performed with sufentanil (4.5 microg kg(-1)
      h(-1)) / flunitrazepam (9 microg kg(-1) h(-1)) infusion (control group); the
      other groups received in addition a loading dose of propofol 2 mg kg(-1) and a
      maintainance infusion of 1-3.5 mg kg(-1) h(-1). MLAEP were evaluated by using
      Pa/Nb-amplitudes and Nb-latencies. Haemodynamics were monitored by ECG, arterial
      blood pressure and cardiac function with pulmonary artery catheterization.
      RESULTS: In the control group, median amplitude of MLAEP decreased by 50% with a
      wide range, but were detectable in >90% of patients throughout surgery. Propofol
      suppressed amplitude Pa/Nb of MLAEP dose dependently. With 3.5 mg kg(-1) h(-1)
      amplitudes disappeared in >40% of patients throughout cardiac surgery. Median Nb
      latencies increased in the control group from 44 to a range from 50 to 60 ms. In
      groups with propofol >2 mg kg(-1) h(-1), Nb-latencies, detectable in the patients
      without complete suppression of MLAEP, increased to median 60 ms. Haemodynamic
      parameters and cardiac function did not differ among the groups. The use of
      vasopressors was not increased even with the highest propofol dose used.
      CONCLUSION: The dose-response effect of propofol on auditory evoked potentials
      reveals that combining a loading dose of 2 mg kg-1 with a consecutive infusion of
      3.5 mg kg(-1) h(-1) significantly suppresses MLAEP during cardiac surgery. Thus,
      auditory information may not be processed and awareness with recall becomes
      unlikely.

PMID- 11576054
TI  - Assessment of the efficacy of esmolol on the haemodynamic changes induced by
      laryngoscopy and tracheal intubation: a meta-analysis.
AB  - BACKGROUND: Adrenergic stress response induced by laryngoscopy and tracheal
      intubation (LTI) appears to be attenuated by esmolol, but its potential clinical
      benefits have not been fully weighed against possible adverse effects. METHODS: A
      systematic search up to May 2000 was performed using MEDLINE, EMBASE, LILACS,
      Cochrane library, manual searching and bibliographies in all languages. All
      randomised comparisons of esmolol with placebo on the haemodynamic changes
      elicited by LTI were obtained. Trials were included in the present meta-analysis
      if they recorded heart rate (HR), systolic pressure (SBP), mean arterial pressure
      (MAP) or diastolic pressure (DBP) at three different stages: pre-induction,
      immediately prior to intubation, and in the post-intubation period. Weighted mean
      differences (WMD) and 95% confidence intervals (CI) of the changes in the
      haemodynamic variables between treatment and placebo groups were calculated.
      RESULTS: Of 72 publications identified, 38 randomised controlled trials
      containing a total of 2009 patients were finally included. Eleven different
      regimens and doses of esmolol demonstrated effectiveness in the attenuation of HR
      and BP after LTI in a dose-dependent manner. The most effective regimen was a
      loading dose of 500 microg x kg(-1) x min(-1) over 4 min followed by continuous
      infusion dose of 200-300 microg x kg(-1) x min(-1) [WMD: 20.2 bpm (95% CI: 15.6
      to 24.7)]. High bolus dose (200 mg) of esmolol produced a considerable decrease
      in DBP [WMD 10.1 mmHg (95% CI: 7.3 to 12.8)]. CONCLUSION: Esmolol is effective,
      in a dose-dependent manner, in the attenuation of the adrenergic response to LTI.
      To minimise its adverse effects it should be administered, when considered
      clinically appropriate, as a continuous infusion regimen.

PMID- 11576055
TI  - Propofol and gastric effects of morphine.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether propofol abolishes
      morphine-induced effects on gastric emptying and gastric tone. METHOD: The study
      was carried out before anesthesia in 40 patients (ASA I-II). Gastric tone was
      measured in 20 patients by an electronic barostat. Volume changes were thereby
      registered continuously in an intragastric flaccid bag with a constant preset
      pressure. All patients received i.v. morphine 0.1 mg x kg(-1) before the
      measurements and, in a randomized order, 10 of the patients also received a bolus
      dose of propofol 1 mg. kg-1 before morphine. Gastric emptying was studied with
      the paracetamol method in 20 patients. All patients received morphine 0.1 mg x
      kg(-1) i.v. 10 min before oral ingestion of 1.5 g paracetamol in 200 ml water
      and, in a randomized order, 10 of the patients also received propofol, a bolus
      dose of 0.3 mg x kg(-1) before morphine, followed by an infusion of 1 mg x kg(-1)
      x h(-1) during the whole study (2 h). RESULTS: The volume in the intragastric bag
      increased in all patients receiving morphine without propofol. In the group that
      received propofol before morphine, the volume in the intragastric bag decreased
      in all patients. The volume differences between the groups were statistically
      significant (P<0.01). There were no statistically significant differences of the
      AUC60, Cmax and Tmax of serum paracetamol concentrations between the morphine and
      propofol-morphine groups. CONCLUSION: Propofol did not abolish morphine-induced
      delay of gastric emptying even if propofol abolished the decrease of gastric tone
      induced by morphine.

PMID- 11576056
TI  - Preoperative blood pressure and intraoperative hypothermia during lower abdominal
      surgery.
AB  - BACKGROUND: Preoperative factors including age and body habitus affect
      intraoperative hypothermia during general anesthesia. We hypothesized that
      preoperative blood pressure also plays a contributory role in the induction of
      intraoperative hypothermia. METHODS: We evaluated the effect of preoperative
      systolic blood pressure (SBP) on core temperature during lower abdominal surgery
      under general anesthesia. In 36 female patients under 65 years of age, patients
      with a preoperative SBP of 140 mmHg or greater upon arrival in the operating
      theater were assigned to the high SBP group (n=18), while those with SBP below
      140 mmHg were assigned to the normal SBP group (n=18). Anesthesia was maintained
      with isoflurane and nitrous oxide combined with epidural buprenorphine, and
      routine thermal care was provided intraoperatively. RESULTS: There were no
      significant differences in age, height or weight between the two groups. Tympanic
      membrane temperature in the normal SBP group started to decrease significantly
      from 15 min after induction of anesthesia compared to that in the high SBP group,
      and continued to decrease further at two hours after induction. Vasoconstriction
      threshold, determined to be tympanic membrane temperature at the time when a
      forearm minus finger skin surface gradient exceeded 0 degrees C, was
      significantly higher in the high SBP group than in the normal SBP group.
      CONCLUSION: These results suggest that preoperative SBP has some preventive
      effect on the decrease in intraoperative core temperature during lower abdominal
      surgery under general anesthesia.

PMID- 11576057
TI  - How do anaesthesiologists treat malignant hyperthermia in a full-scale
      anaesthesia simulator?
AB  - BACKGROUND: Clinical malignant hyperthermia (MH) is rare and usually occurs
      unexpectedly. Prompt diagnosis and correct treatment is crucial for survival of
      the patient developing fulminant MH. The aims of the present study were to
      investigate whether anaesthesiologists could make a correct diagnosis of MH and
      to evaluate their treatment of fulminant MH in a simulator. METHODS: Thirty-two
      teams (one anaesthesiologist/one nurse anaesthetist) were exposed to an event of
      clinical MH in a full-scale simulator. Their performance was videotaped for
      retrospective analysis of the treatment on the basis of the recommendations of
      the Danish Malignant Hyperthermia Register. RESULTS: All 32 teams asked the
      surgeon to terminate the surgery as fast as possible, switched off the vaporiser
      and administered 100% oxygen. Although all intended to hyperventilate the
      patient, only 14 teams actually managed to perform the hyperventilation. Most
      problems were found in teams that switched to manual ventilation. All teams
      treated the patient with dantrolene, and symptomatic treatment was initiated by
      all even though some elements of the full treatment were lacking, possibly due to
      the limited time available. CONCLUSION: All teams diagnosed MH in the simulator
      satisfactorily. The surprising negative finding was that more than half of the
      participants failed to hyperventilate the "patient" although they intended to do
      so. This investigation shows that the problem in these teams' treatment of MH was
      more a question of practical management of the resources than lack of theoretical
      knowledge.

PMID- 11576058
TI  - Probability of acceptable intubation conditions with low dose rocuronium during
      light sevoflurane anaesthesia in children.
AB  - BACKGROUND: To define the rocuronium doses which would provide 50%, 90%, and 95%
      probability of 'acceptable' intubation conditions during light sevoflurane
      anaesthesia, we studied 60 children aged 2-7 years in a prospective, randomised,
      assessor blinded study. METHODS: After mask ventilation with 1 MAC
      sevoflurane/N2O for 17+/-1 (x+/-SD) min we administered rocuronium (either 0.15,
      0.22, 0.3, 0.5, or 1.0 mg. kg(-1)) or placebo, and quantified the evoked force of
      the adductor pollicis muscle. Intubation conditions were assessed before and 2
      min after injection of the test drug. RESULTS: Intubation conditions were
      improved significantly with rocuronium and scored 'acceptable' in 70%, 90%, and
      100% of the children after injection of rocuronium 0.15, 0.22, and 0.3 mg x kg(
      1), respectively. In parallel, twitch tension decreased to 53% (6-100), 26% (11
      100), and 11% (0-19) of baseline (median (range)). Recovery of train-of-four
      ratio to 0.8 was achieved 13 (7-19), 16 (8-28), and 27 (23-44) min after
      injection of the respective rocuronium doses. Higher rocuronium doses did not
      further improve intubation conditions but only prolonged time of neuromuscular
      recovery. Logistic regression analysis revealed that rocuronium 0.11 (CI 0.05
      0.16), 0.21 (0.14-0.28), and 0.25 (0.15-0.34) mg x kg(-1) provides a 50%, 90%,
      and 95% probability of 'acceptable' intubation conditions in children during 1
      MAC sevoflurane/N2O anaesthesia, respectively. Furthermore, we calculated that
      force depression of adductor pollicis muscle to 81% (CI 72-90), 58% (42-74), and
      50% (29-71) of baseline is associated with 50%, 90%, and 95% probability of
      'acceptable' intubation conditions. CONCLUSIONS: Submaximal depression of muscle
      force with low dose rocuronium improves intubation conditions in children during
      light sevoflurane anaesthesia while allowing rapid recovery of neuromuscular
      function. However, when using low dose rocuronium neuromuscular monitoring may be
      helpful to detect children with inadequate response to the relaxant so as to
      avoid an unsuccessful intubation attempt.

PMID- 11576059
TI  - Vocal cord paralysis as a consequence of peritonsillar infiltration with
      bupivacaine.
AB  - Reduction of postoperative pain is an important goal in the perioperative
      management of tonsillectomy patients. This is particularly the case for children,
      who often exhibit resistance to intramuscular or rectal administration of drugs.
      Peritonsillar bupivacaine infiltration, a relatively safe method of pain control,
      is in some centers frequently used by otolaryngologists for pain relief. We
      present the case of a 5-year-old girl who developed bilateral vocal cord
      paralysis following preoperative peritonsillar bupivacaine infiltration. After an
      uneventful tonsillectomy and extubation, stridor and respiratory distress
      developed. Bilateral vocal cord paralysis was seen on laryngoscopy. The patient
      was reintubated and five hours later was successfully extubated without further
      sequelae. Anesthesiologists and surgeons should be aware of this uncommon
      complication than can occur with the use of peritonsillar bupivacaine
      infiltration for pain control in tonsil surgery.

PMID- 11576060
TI  - Bilateral eye hemorrhage after laparoscopic cholecystectomy.
AB  - A case of bilateral eye hemorrhage after laparoscopic cholecystectomy, probably
      caused by an increase in venous blood pressure due to carbon dioxide
      insufflation, is reported.

PMID- 11576061
TI  - Direct tracheal airway pressure measurements.

PMID- 11576063
TI  - Neuroexcitatory symptoms after propofol: a phenol related neurotoxic effect?

PMID- 11576064
TI  - Post-operative pancreatitis after propofol administration.

PMID- 11576065
TI  - The palm print as predictor of difficult intubation.

PMID- 11576066
TI  - Thrombolytic therapy in sustained ventricular fibrillation.

PMID- 11576067
TI  - Single injection paravertebral block.

PMID- 11576069
TI  - Inhaled steroids and local side-effects.

PMID- 11576070
TI  - Molecular mechanisms of corticosteroids in allergic diseases.

PMID- 11576071
TI  - Predictive testing in contact allergy: facts and future.

PMID- 11576072
TI  - Local side-effects of inhaled corticosteroids in asthmatic children: influence of
      drug, dose, age, and device.
AB  - BACKGROUND: The objective was to investigate the local side-effects of inhaled
      corticosteroids (ICS) in daily life in asthmatic children, particularly the
      younger ones, by an observational prospective cross-sectional cohort study.
      METHODS: Asthmatic children (n=639, 75.9+/-48.9 months, 61.3% boys), treated with
      beclomethasone dipropionate (BDP) (721.0+/-287.3 microg per day) or budesonide
      (BUD) (835.5+/-684.9 microg per day) for at least 1 month, were recruited at the
      time of a scheduled visit. Local side-effects were researched by questionnaire
      (cough during inhalation, hoarseness, dysphonia, and thirsty feeling) and
      clinical examination (perioral dermatitis, oral candidiasis, and tongue
      hypertrophy). RESULTS: Exactly 63.3% of the children aged under 6 years and 59.5%
      of the older ones reported one local side-effect. Cough (39.7%) was dependent on
      young age, use of BDP, and mainly use of spacer device, with an OR of 4.7 (95%
      CI: 2.7-8.2). Thirsty feeling (21.9%) and hoarseness (14.1%) occurred in children
      using ICS and long-acting beta2-agonists. Dysphonia (11.1%) was favored by high
      doses of BDP and BUD, and by inhalation from spacer devices or nebulizers. No
      factor favored oral candidiasis (10.7%). Perioral dermatitis (2.9%) and tongue
      hypertrophy (0.1%) were associated with nebulization. CONCLUSION: Local side
      effects of ICS are common in asthmatic children of all ages, and the device used
      constitutes the most influential factor.

PMID- 11576073
TI  - Prolonged nasal eosinophilia in allergic patients after common cold.
AB  - BACKGROUND: Viral respiratory tract infections may cause both harmless common
      colds and severe asthma exacerbations; the differences in disease expression
      probably depend on the allergic status of the patient. To determine whether
      altered immunologic mechanisms underlie these differences, we investigated nasal
      inflammation during naturally acquired common cold. METHODS: In a group of 16
      patients (eight allergic), nasal brush samples were taken, and nasal symptoms
      were recorded during common cold, 2 weeks later (convalescence), and at baseline
      (>4 weeks without nasal symptoms). Nasal brush cells were stained
      immunohistochemically for Langerhans cells, T cells, monocytes, neutrophils, B
      cells, macrophages, natural killer (NK) cells, mast cells, eosinophils, eotaxin,
      and RANTES. RESULTS: Four rhinovirus, four coronavirus, three RSV, one Mycoplasma
      pneumoniae, and one influenza A/enterovirus double infection were confirmed.
      Increased numbers of T cells, monocytes, macrophages, NK cells, eosinophils, and
      RANTES- and eotaxin-positive cells, but not neutrophils, were observed during
      common cold in allergic and nonallergic patients, and increased numbers of mast
      cells in allergic patients. Compared to nonallergic patients, in allergic
      patients eosinophil influx persisted into convalescence. CONCLUSION: Prolonged
      nasal eosinophil influx was observed in allergic patients after common cold. What
      immunologic factors can induce prolonged eosinophil influx and whether this may
      increase the risk of subsequent allergen-induced hypersensitivity reactions must
      be studied further.

PMID- 11576074
TI  - Generic or disease-specific quality of life scales to characterize health status
      in allergic rhinitis?
AB  - BACKGROUND: In patients with allergic rhinitis (AR), various instruments have
      been validated for the measurement of quality of life (QOL), which may be greatly
      reduced. However, it is not clear which QOL instruments should be used for the
      different types of AR and whether they are sensitive to treatment. METHODS: The
      QOL of patients suffering from symptomatic seasonal AR (sSAR) (before and during
      treatment with a topical or systemic antihistamine), symptomatic perennial AR
      (sPAR), and asymptomatic seasonal AR (aSAR) was determined with the
      Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) as disease specific and
      with the Munich Life Dimension List (MLDL) and the Visual Analogue Scale for
      Quality of Life (VAS-QOL) as generic QOL instruments. RESULTS: The different
      forms of AR were associated with typical QOL patterns. In sSAR, we found severe
      limitation of the global QOL, reduced global life satisfaction, high ranking of
      practical problems, high limitation of activity, and a high degree of disturbance
      in all subscales of the RQLQ. In sPAR, there were moderate limitation of the
      global QOL, normal global life satisfaction, high ranking of practical problems,
      moderate limitation of activity, and a high degree of disturbance by common
      symptoms. Under antihistamine treatment, both systemic and nasal, a significant
      improvement of QOL parameters was found, reaching the levels of patients with
      aSAR after 2 weeks. CONCLUSION: QOL instruments can distinguish the impairment
      resulting from sSAR from that of sPAR and are sensitive to treatment with topical
      and systemic antihistamines. However, as the RQLQ was not designed to measure the
      short-term variations of disease status that appear in SAR, it may not
      demonstrate the rapid improvement of QOL under antihistamine treatment.

PMID- 11576075
TI  - Working with male rodents may increase risk of allergy to laboratory animals.
AB  - BACKGROUND: Our aim was to study the risk of laboratory animal allergy (LAA)
      among research staff working in laboratories separate from the animal confinement
      area. The roles of atopy and exposure intensity in LAA were studied with special
      regard to exposure to male rodents, who excrete higher levels of urinary
      allergens than female rodents. METHODS: Eighty rodent-exposed subjects gave blood
      samples for the analysis of total IgE, Phadiatop, and specific IgE against rat
      (RUA) and mouse urinary allergens (MUA), and answered questionnaires. Air samples
      were collected for RUA and MUA aeroallergen measurement in both laboratories and
      animal confinement facilities. RESULTS: Twenty percent of the subjects had IgE
      >0.35 kU/l to RUA and/or MUA, and 32% had experienced animal work-related
      symptoms, although 90% of aeroallergen samples from the research department
      laboratories were below the detection limit (<0.26 ng RUA per m(3) and <0.8 ng
      MUA per m(3)). Atopy (positive Phadiatop), total IgE >100 kU/l, other allergies
      (especially to other animals), or more than 4 years of exposure significantly
      increased laboratory animal sensitization and symptoms. Working with mainly male
      rodents gave odds ratios (95% CI) of 3.8 (0.97-15) for sensitization and 4.4 (1.4
      14) for symptoms. Subjects with both exposure to mainly male rodents and atopy or
      elevated total IgE had a 10-fold higher frequency of sensitization than exposed
      subjects with neither risk factor. CONCLUSION: A majority of subjects with a
      combination of exposure to mainly male rodents and atopy or elevated total IgE
      developed sensitization to and symptoms from laboratory animals. Current low
      exposure seems to maintain the presence of specific IgE. Further measures must be
      undertaken to provide a safe workplace for laboratory animal workers.

PMID- 11576076
TI  - Asthma in relation to personality traits, life satisfaction, and stress: a
      prospective study among 11,000 adults.
AB  - BACKGROUND: While patients' personality has been thought to affect allergic
      diseases, the association of asthma and psychological factors is still debated.
      Stress is believed to predispose to asthma, but no clear evidence of causality
      has been found. We have studied the role of psychological factors in prevalent as
      well as in incident asthma cases among the adult population. METHODS: A total of
      11540 adults initially aged 18-45 years responded to three questionnaires in
      1975, 1981, and 1990, respectively. The association of psychological factors
      (including extroversion and neuroticism scales, subjective stress, and life
      satisfaction) and prevalent asthma was studied, as well as the predisposing
      effect of these factors on the risk of adult onset asthma. Logistic regression
      was used for risk calculations. RESULTS: Low life satisfaction was associated
      with asthma prevalence (age- and sex-adjusted OR=2.27: 1.04-4.93 for prevalent
      asthma among those with low life satisfaction compared to those with high life
      satisfaction), as was neuroticism (age and sex-adjusted OR=1.78:1.12-2.84 for
      those with a high neuroticism score compared to those with a low score). A high
      extroversion score was significantly associated with the risk of adult onset
      asthma among women (age-adjusted OR=2.72: 1.44-5.12 for new asthma among those
      with high score compared to those with a low extroversion score). CONCLUSION: No
      specific personality type is associated with adult onset asthma, but there is a
      significant sex difference in the effect of psychological factors in asthma risk.
      A high extroversion score is a strong predictor of incident asthma among women.
      Prevalent asthma decreases life satisfaction and is associated with a high
      neuroticism score.

PMID- 11576077
TI  - Rapid isolation, characterization, and glycan analysis of Cup a 1, the major
      allergen of Arizona cypress (Cupressus arizonica) pollen.
AB  - BACKGROUND: A rapid method for the purification of the major 43-kDa allergen of
      Cupressus arizonica pollen, Cup a 1, was developed. METHODS: The salient feature
      was a wash of the pollen in acidic buffer, followed by an extraction of the
      proteins and their purification by chromatography. Immunoblotting, ELISA, and
      lectin binding were tested on both the crude extract and the purified Cup a 1.
      Biochemical analyses were performed to assess the Cup a 1 isoelectric point, its
      partial amino-acid sequence, and its glycan composition. RESULTS: Immunochemical
      analysis of Cup a 1 confirmed that the allergenic reactivity is maintained after
      the purification process. Partial amino-acid sequencing indicated a high degree
      of homology between Cup a 1 and allergenic proteins from the Cupressaceae and
      Taxodiaceae families displaying a similar molecular mass. The purified protein
      shows one band with an isoelectric point of 5.2. Nineteen out of 33 sera (57%)
      from patients allergic to cypress demonstrated significant reactivity to purified
      Cup a 1. MALDI-TOF mass spectrometry indicated the presence of three N-linked
      oligosaccharide structures: GnGnXF(3) (i.e., a horseradish peroxidase-type
      oligosaccharide substituted with two nonreducing N-acetylglucosamine residues),
      GGnXF(3)/GnGXF(3) (i.e., GnGnXF with one nonreducing galactose residue), and
      (GF)GnXF(3)/Gn(GF)XF(3) (with a Lewisa epitope on one arm) in the molar ratio
      67:8:23. CONCLUSION: The rapid purification process of Cup a 1 allowed some fine
      studies on its properties and structure, as well as the evaluation of its IgE
      reactivity in native conditions. The similarities of amino-acid sequences and
      some complex glycan stuctures could explain the high degree of cross-reactivity
      among the Cupressaceae and Taxodiaceae families.

PMID- 11576078
TI  - Comparison of the effects of levocetirizine and loratadine on histamine-induced
      wheal, flare, and itch in human skin.
AB  - BACKGROUND: This randomized, double-blind, crossover study compared the effects
      of the R-enantiomer of cetirizine, levocetirizine, with those of loratadine on
      the wheal, flare, and itch response to histamine in human skin. METHODS:
      Levocetirizine (5 mg), loratadine (10 mg), or placebo was taken orally 4 h before
      the intradermal injection of histamine (20 microl, 100 microM) or the control
      vehicle into the forearm skin of healthy volunteers. Flare areas were assessed by
      scanning laser Doppler imaging before and at 30-s intervals for a period of 9
      min. Wheal areas were measured by planimetry at 10 min. Itch was scored every 30
      s with a visual analogue scale. RESULTS: After placebo administration, the mean
      peak flare area was 23.01+/-1.94 cm(2), the wheal area 248+/-27 mm(2), and the
      cumulative itch score 28.8+/-4.6% (mean+/-SEM). Levocetirizine reduced the flare,
      wheal, and itch by 60%, 68%, and 91%, respectively (all P<0.001, Student's t-test
      for paired data). The effects of loratadine were variable and not statistically
      significant. CONCLUSION: Levocetirizine (5 mg) is a potent inhibitor of the
      effects of histamine in human skin with an efficacy that exceeded that of
      loratadine (10 mg) when single doses of the drugs were administered 4 h before
      the test.

PMID- 11576079
TI  - Safety of sublingual immunotherapy with monomeric allergoid in adults:
      multicenter post-marketing surveillance study.
AB  - BACKGROUND: Sublingual immunotherapy (SLIT) appears to be acceptably safe in
      clinical trials, but post-marketing data are needed to provide essential
      information. This study specifically evaluated the safety of commercial SLIT in
      adult patients in a post-marketing phase. METHODS: A total of 198 patients (83
      male, 115 female, mean age 24.4 years) receiving SLIT for respiratory allergy
      were followed up for 3 years by a specific questionnaire for side-effects. SLIT
      (LAIS, Lofarma SpA, Milan, Italy), a monomeric allergoid in tablets, was
      administered, in association with drug therapy, pre- or pre-coseasonally for
      pollen and continuously for mites. The average duration was 12-36 months, and the
      total of doses was about 32 800. Side-effects were grouped as ocular,
      gastrointestinal, rhinitis, asthma, urticaria, edema of tongue/lips, and
      anaphylaxis. The severity was graded as low (no need for treatment or dose
      adjusting, no interference with activities), moderate (interference with
      activities/need for drugs/SLIT discontinuation), and severe (life
      threatening/hospitalization/emergency care). RESULTS: Seventeen events
      corresponding to 7.5% of patients and 0.52 per 1000 doses were reported. Seven
      episodes of rhinitis (two in two patients), three of oral itching, and one of
      abdominal pain were self-limiting. Two cases of urticaria and two of abdominal
      pain/nausea were controlled by a temporary dose-adjustment, and one case of
      urticaria and conjunctivitis required oral antihistamines. Medical intervention
      was needed in six patients only during a 3-year period. CONCLUSION: The results
      of this study, performed in a real situation of clinical practice, confirm the
      satisfactory safety profile of SLIT.

PMID- 11576080
TI  - Comparison of quantitative ELISA and semiquantitative Dustscreen for
      determination of Der p 1, Der f 1, and Fel d 1 in domestic dust samples.
AB  - BACKGROUND: Quantitative ELISA kits used for the measurement of indoor allergens
      are time-consuming. Therefore, an immunodot assay (Dustscreen) has been
      introduced, so that results can be obtained within 4 h. In order to assess the
      potential applications of the new method, we compared quantitative ELISA methods
      and Dustscreen. METHODS: We compared the measurements of the mite allergens Der p
      1 and Der f 1, and Fel d 1 by both Dustscreen and one brand of ELISA in 82 dust
      samples, and we also compared the measurement of the cat allergen Fel d 1 by
      Dustscreen and a different brand of ELISA in 77 dust samples. Optimum dilutions
      of dust extracts were compared between the ELISA and the immunodot assay. The
      nonparametric coefficient of correlation (Spearman's rank) was calculated for
      each allergen. RESULTS: The immunodot assay was easy to perform. There was a good
      correlation between the results of the ELISA and Dustscreen (Der p 1: r=0.98, Der
      f 1: r=0.93, and Fel d 1: r=0.98). However, the coefficient of variation varied
      between 50% and 100% for Fel d 1 above 100 000 ng/g in Dustscreen. No cockroach
      allergen (Bla g 2) was detected in domestic dust samples in Berlin, and lower
      concentrations of group 2 allergen of mite (from not detectable to 19 500 ng/gm;
      median concentration 2000 ng/g) were found than mite group 1 allergens (sum of
      Der p 1 plus Der f 1: median 12 350 ng/g, minimum n.d., maximum 153 120 ng/g).
      CONCLUSION: Our results indicate that quantification of indoor allergens in house
      dust samples can be performed easily with Dustscreen, and both the technology and
      methodology are satisfactory.

PMID- 11576081
TI  - Increased plasma eotaxin in atopic dermatitis and acute urticaria in infants and
      children.
AB  - BACKGROUND: The previously reported eotaxin overexpression in the lesional skin
      of atopic dermatitis (AD) led us to the assumption that circulating levels of
      eotaxin may be elevated too. We sought to investigate the plasma expression of
      eotaxin in children with skin allergy in relation to clinical activity and type
      of lesions. METHODS: Plasma eotaxin was assayed in 78 infants and children, of
      whom 16 had AD, 19 had acute urticaria (AU), and 43 were healthy matched
      subjects. Seven children in the group of AU were resampled for plasma eotaxin
      after clinical remission. RESULTS: The plasma eotaxin levels in AD (median=158
      pg/ml, mean [SD]=168 [61] pg/ml) were significantly higher than the control
      values (median=60 pg/ml, mean [SD]=59.5 [18.5] pg/ml). Not only did patients with
      AU demonstrate elevated plasma eotaxin levels (median=126 pg/ml, mean [SD]=124
      [33] pg/ml), but also a significant decline occurred on follow-up. The
      coexistence of angioedema with AU did not cause any further increase in plasma
      eotaxin expression. Plasma eotaxin levels were significantly higher in AD than in
      AU, probably reflecting the chronic nature of eczematous AD lesions. The plasma
      eotaxin levels did not correlate with serum total IgE, peripheral blood absolute
      eosinophil count, or age of the patients. However, there was a positive
      correlation between age and plasma eotaxin in the control group. CONCLUSION: Our
      findings imply that circulating levels of eotaxin increase in AD and during
      flares of AU, probably to serve in the recruitment and activation of eosinophils.
      It may also represent a biomarker of lesional activity.

PMID- 11576082
TI  - Serum CD23 is not altered in gastroallergic anisakiasis, but correlates with the
      production of specific IgE and the amount of polyclonal stimulation.
AB  - BACKGROUND: Previous studies have shown elevated serum levels of the cytokines IL
      4 and sCD23 in atopic patients and parasitic disease. Gastroallergic anisakiasis
      is an acute parasitic disease, accompanied by IgE-mediated clinical symptoms and
      an important increase of specific and total IgE. METHODS: Sixteen patients with
      acute urticaria/angioedema due to parasitism by Anisakis simplex after intake of
      raw or undercooked fish were selected, and serum samples were taken in the
      emergency room within 24 h (day 0; n=16), after 1 month (n=16), and after 6
      months (n=10). Serum samples were studied for specific IgE against A. simplex,
      total IgE, sCD23, and IL-4. RESULTS: Mean values for sCD23 did not change in the
      observation period. Only 4/16 serum samples showed measurable IL-4 levels.
      Specific IgE and total IgE levels were found to be elevated after 1 month; after
      6 months, they fell to nearly basal values. There was a positive correlation
      between sCD23 and specific IgE at day 0 and follow-up (r=0.55-0.69, P<0.026); a
      positive correlation between sCD23 and total IgE (r=0.54-0.62, P<0.056). Basal
      sCD23 could moderately predict the percentual increment of total IgE in the first
      month (r=0.56, P<0.038). CONCLUSION: Thus, it seems that interindividual
      variability of sCD23 is an important factor, with higher values predisposing to
      more production of unrelated IgE, independently of the parasite's action.

PMID- 11576083
TI  - Occupational allergic contact urticaria to yucca (Yucca aloifolia), weeping fig
      (Ficus benjamina), and spathe flower (Spathiphyllum wallisii).
AB  - BACKGROUND: Occupational contact urticaria (CU) from plants is often reported,
      but it is less often attributed to decorative houseplants. We present an atopic
      gardener and caretaker of plants who developed CU when occupationally exposed to
      weeping fig, spathe flower, and yucca. METHODS: Sensitization was evaluated by
      skin prick tests (SPT) and analyses for IgE antibodies. RESULTS: SPT were
      positive to all three plants, and IgE antibodies were found to weeping fig and
      spathe flower. SPT were also performed with several decorative houseplants in
      more than 600 patients. Positive SPT was found to weeping fig (12%), African milk
      tree (8.3%), yucca (5.8%), Chinese rose (4.7%), massangana (4.6%), bird's nest
      fern (3.2%), and spathe flower (3.2%). CONCLUSION: Our study indicates that SPT
      and tests for IgE antibody are useful in detecting occupational CU caused by
      houseplants.

PMID- 11576084
TI  - The effect of sieving on Der p 1 levels.

PMID- 11576085
TI  - Allergic contact dermatitis to henna.

PMID- 11576086
TI  - Allergy to cow bone dust.

PMID- 11576087
TI  - Delayed exanthema to nonionic contrast medium.

PMID- 11576088
TI  - Basotest and suxamethonium allergy.

PMID- 11576089
TI  - Rofecoxib safe in NSAID hypersensitivity.

PMID- 11576090
TI  - Sensitization to rubber additives.

PMID- 11576091
TI  - Anaphylaxis to buckwheat.

PMID- 11576092
TI  - The acute pain service: a model for outreach critical care.

PMID- 11576093
TI  - Acupuncture versus ondansetron in the prevention of postoperative vomiting. A
      study of children undergoing dental surgery.
AB  - This study compares the anti-emetic effect of acupuncture with that of
      ondansetron and a placebo. Ninety children undergoing dental treatment under
      general anaesthesia were randomly allocated to one of the three equal groups, to
      receive acupuncture needle insertion, intravenous ondansetron 0.15 mg x kg(-1) or
      a placebo. Parental satisfaction scores and the incidence of emetic episodes were
      recorded. A significant difference was found in the number of patients who
      vomited and the total number of the emetic episodes when comparing the two
      treatment groups with the placebo group (p < 0.0001). A significant difference
      was also found between the treatment groups and the placebo group with respect to
      parental satisfaction score (p < 0.03). We conclude that traditional Chinese
      acupuncture is a valid non-pharmacological alternative anti-emetic treatment that
      can be recommended as a prophylactic technique in children undergoing dental
      surgery under general anaesthesia.

PMID- 11576094
TI  - Speed of collapse of the non-ventilated lung during one-lung anaesthesia: the
      effects of the use of nitrous oxide in sheep.
AB  - By enhancing gaseous uptake from the non-ventilated lung during procedures
      performed thoracoscopically, the rapid diffusion properties of nitrous oxide
      would be expected to speed lung collapse and so facilitate surgery. To assess the
      effect of nitrous oxide on the speed of absorptive lung collapse, a study was
      conducted using 11 anaesthetised sheep. Speed of collapse was assessed in an
      indirect manner by recording the time required in a closed-chest situation for
      the airway pressure distal to a single lung airway occlusion to decrease to - 1.0
      kPa. The influence of nitrous oxide was assessed by comparing the time taken for
      this decrease in airway pressure when the animal was being mechanically
      ventilated with 50% nitrous oxide in oxygen with the time taken when using 100%
      oxygen. In all assessments, it was found that the decrease in airway pressure to 
      1.0 kPa occurred in a shorter time when nitrous oxide was used. The findings
      lend support to the hypothesis that during thoracoscopic surgery, mechanical lung
      ventilation with an oxygen/nitrous oxide mixture will increase the rate of
      gaseous uptake from the non-ventilated lung and so hasten its absorptive
      collapse.

PMID- 11576095
TI  - Speed of collapse of the non-ventilated lung during single-lung ventilation for
      thoracoscopic surgery: the effect of transient increases in pleural pressure on
      the venting of gas from the non-ventilated lung.
AB  - A study of 10 anaesthetised patients placed in the lateral position for
      thoracoscopic surgery assessed whether transient increases in pleural pressure on
      the side of the non-ventilated lung might increase the speed at which gas vents
      from that lung. The transient increases in pleural pressure were generated by the
      mediastinal displacement that occurs with each inspiratory phase of positive
      pressure ventilation of the dependent lung. When combined with a unidirectional
      valve allowing gas to flow out of the non-ventilated lung, and a second valve
      allowing ambient airflow into, but not out of, the thoracic cavity via an initial
      thoracoscopy access site, this mediastinal displacement could conceivably serve
      to 'pump' gas out of the non-ventilated lung. Using the four different
      combinations of valve inclusion or omission, the volume of gas that vented from
      the non-ventilated lung into a measuring spirometer was recorded during a 120-s
      measurement sequence. It was found that the speed of venting was not increased by
      the transient increases in pleural pressure, and that in all but one of a total
      of 34 measurement sequences, venting had ceased by the end of the sequence. Gas
      venting was a mean (SD) of 85.5 (11.9)% complete in 25 s (five breaths), and 96.6
      (6.1)% complete in 60 s. This prompt partial lung collapse very likely reflected
      the passive elastic recoil of the lung, while the failure of transient increases
      in pleural pressure to result in ongoing venting of gas was probably a
      consequence of airways closure as the lung collapsed. It is concluded that
      techniques that aim to speed lung collapse by increasing pleural pressure are
      unlikely to be effective.

PMID- 11576096
TI  - The influence of nitroglycerin and prostaglandin E1 on dynamic cerebral
      autoregulation in adult patients during propofol and fentanyl anaesthesia.
AB  - We investigated dynamic cerebral autoregulation in 24 normocapnic adult patients
      during propofol and fentanyl anaesthesia. Hypotension was induced, to a mean
      arterial pressure (MAP) of 60-65 mmHg, using nitroglycerin or prostaglandin E1.
      Time-averaged mean cerebral blood flow velocity in the right middle cerebral
      artery was measured continuously using transcranial Doppler sonography. Dynamic
      autoregulatory response was activated by a sudden decrease in MAP following
      release of bilateral thigh cuffs (thigh cuff test) and evaluated as a dynamic
      rate of autoregulation (dRoR in % x s(-1)). The cuff test was repeated to obtain
      two values of dRoR during baseline and during induced hypotension; the data were
      then averaged. The mean value of dRoR during baseline and during induced
      hypotension was 14.2 (2.9) and 14.2 (1.6) % x s(-1), respectively, in the
      nitroglycerin group, and 14.6 (2.6) and 14.4 (2.4) % x s(-1), in the
      prostaglandin E1 group. We were unable to demonstrate significant between- or
      within-group differences in dRoR. Thus, we conclude that nitroglycerin and
      prostaglandin E1 do not attenuate dynamic cerebral autoregulation.

PMID- 11576097
TI  - Fenoldopam: renal and splanchnic effects in patients undergoing coronary artery
      bypass grafting.
AB  - Impairment of renal and splanchnic perfusion during and after cardiopulmonary
      bypass may be responsible for acute renal failure and endotoxin-mediated systemic
      inflammation, respectively. We hypothesised that fenoldopam, a selective dopamine
      receptor agonist, would preserve renal function after cardiopulmonary bypass
      through its selective renal vasodilatory and natriuretic effects, and increase
      gastrointestinal mucosal perfusion by selective splanchnic vasodilation. We
      examined the effects of fenoldopam on haemodynamic parameters, creatinine
      clearance, fractional excretion of sodium, urine output, free water clearance and
      gastric mucosal pH in 31 patients undergoing elective coronary revascularisation.
      Patients were randomly assigned to receive continuous infusions of fenoldopam 0.1
      microg x kg(-1) x min(-1) (n = 16) or placebo (n = 15). Renal parameters were
      measured: during a 24-h period before hospital admission, during cardiopulmonary
      bypass, from completion of cardiopulmonary bypass until 4 h later, from 4 to 8 h
      after cardiopulmonary bypass, and from 8 to 14 h after cardiopulmonary bypass.
      Gastric intramucosal pH was measured using a gastric tonometer before, during and
      after cardiopulmonary bypass. In the placebo group, but not the fenoldopam group,
      mean (SD) creatinine clearance decreased after separation from cardiopulmonary
      bypass, from 107 (36) to 71 (22) ml x min(-1) (p < 0.01) and from 107 (36) to 79
      (26) ml x min(-1) (p < 0.01) for the 0-4 h and 4-8 h intervals after
      cardiopulmonary bypass, respectively. Changes in intramucosal pH were similar in
      both groups. The findings are consistent with the hypothesis that fenoldopam
      possesses a renoprotective effect in patients undergoing cardiopulmonary bypass.

PMID- 11576098
TI  - Bloodletting acupuncture for the prevention of stridor in children after tracheal
      extubation: a randomised, controlled study.
AB  - Bloodletting acupuncture has been used for the treatment of a variety of upper
      respiratory tract problems, especially those of laryngeal origin. This study
      assesses its efficacy in reducing the incidence of stridor after tracheal
      extubation in children undergoing general anaesthesia with halothane. Sixty
      children were randomly allocated to an acupuncture group and a control group. In
      the acupuncture group, bloodletting acupuncture was performed before extubation.
      A blinded observer determined the presence and severity of postextubation
      stridor. The incidence of stridor in the acupuncture group was significantly
      higher than in the control group. In addition, the severity of stridor was
      significantly greater in the acupuncture group. It is concluded that in children
      undergoing halothane anaesthesia, the incidence of postextubation stridor cannot
      be reduced by bloodletting acupuncture.

PMID- 11576099
TI  - Pharmaceutics for the anaesthetist.
AB  - Pharmaceutics is that branch of science concerned with the manufacture and
      formulation of pharmaceutical products, and is a subject almost exclusively in
      the domain of pharmacists and those concerned with pharmaceutical manufacture.
      However, there are some aspects of pharmaceutics that are of particular
      importance to the anaesthetist, such as the pharmacology of the various
      preservatives, antimicrobials and other additives found in anaesthetic products,
      and an understanding of basic processes such as emulsification and
      lyophylisation. This review aims to survey those areas.

PMID- 11576100
TI  - Compartment syndrome associated with the Lloyd Davies position. Three case
      reports and review of the literature.
AB  - The Lloyd Davies position was developed to facilitate access to the pelvis for
      gynaecological, urological and colorectal procedures. Previous case reports have
      demonstrated that prolonged adoption (> 4 h) of this position has been associated
      with the development of bilateral compartment syndrome of the calves. All three
      patients reported here suffered severe bilateral calf pain despite the use of
      thoracic epidurals. All three cases required three-compartment fasciotomies and,
      6 months after surgery, were all still severely disabled as a consequence of the
      compartment syndrome. These case reports stress the dangers of use of the Lloyd
      Davies position for prolonged procedures and demonstrate that some patients are
      at risk after relatively short periods (< 3 h). Previous case reports and
      clinical studies have focused on the effect of limb elevation in stirrups on the
      arterial pressure in the lower limb. We review the pathophysiology of compartment
      syndrome and consider factors other than a decrease in arterial pressure that may
      predispose to compartment syndrome during adoption of the Lloyd Davies position.

PMID- 11576101
TI  - A survey of pre-operative optimisation of high-risk surgical patients undergoing
      major elective surgery.
AB  - Pre-operative optimisation of high-risk patients undergoing major elective
      surgery has been shown to decrease peri-operative morbidity and mortality. It is
      also cost effective because of the resulting decrease in postoperative
      complications. A questionnaire was sent to 170 intensive care and high dependency
      units in Britain in order to quantify the number of units practising pre
      operative optimisation. There was a 91% response rate. Of the respondents
      familiar with the evidence advocating pre-operative optimisation, 91% believe pre
      operative optimisation improves outcome but only 62% admit patients for such
      preparation. Moreover, only eight units (6%) admit more than 25% of eligible
      patients. The reasons given for not admitting such patients pre-operatively are a
      lack of manpower, beds or both. This survey demonstrates the need for greater
      investment of resources into intensive care and high dependency units, so that
      clinicians can deliver high-quality evidence-based healthcare in accordance with
      the principles of clinical governance.

PMID- 11576102
TI  - Oral midazolam premedication for day case breast surgery, a randomised
      prospective double-blind placebo-controlled study.
AB  - We conducted a randomised prospective double-blind placebo-controlled study to
      assess the efficacy of oral midazolam premedication in 50 ASA I and II female
      patients scheduled to undergo day case breast surgery. Anxiety was assessed using
      100-mm visual analogue scales (VAS) and The State-Trait Anxiety Inventory (STAI)
      psychometric questionnaire. Midazolam premedication did not significantly reduce
      either VAS or STAI score, although heart rate and systolic arterial pressure
      immediately before induction of anaesthesia were significantly lower in patients
      who received midazolam (p = 0.006 and 0.039, respectively). Induction of
      anaesthesia was achieved with a lower dose of propofol (p = 0.0009) and excellent
      (Grade I) conditions for insertion of a laryngeal mask airway were achieved more
      often after midazolam premedication (p = 0.038). Arterial desaturation during
      induction of anaesthesia and insertion of a laryngeal mask airway occurred more
      often in patients who received placebo (p = 0.022). There was a good correlation
      between VAS and STAI used to assess the anxiolytic effects of premedication.
      (Spearman coefficient 0.58, p < 0.0001).

PMID- 11576103
TI  - Tracking the early acquisition of skills by trainees.
AB  - A form of sequential analysis has been developed to track performance of tracheal
      intubation by novice intubators. One hundred and nineteen trainees completed
      logbooks during their attachment to the Departments of Anaesthesia and these data
      were used to produce rates of success for sequential attempts at the procedure. A
      grid was created from this on which future trainees could report their
      performance. A boundary drawn on the grid can be used as a trigger to indicate
      the need for more basic instruction.

PMID- 11576104
TI  - Effect of nitrous oxide on the bispectral index and the 95% spectral edge
      frequency of the electroencephalogram during surgery.
AB  - We studied the effect of nitrous oxide on the bispectral index and 95% spectral
      edge frequency of the electroencephalogram in 20 patients undergoing lumbar
      surgery under general anaesthesia combined with epidural administration of 5 mg
      morphine. Anaesthesia was induced with propofol and sufentanil, and maintained
      with sevoflurane in air/oxygen adjusted to keep the bispectral index between 40
      and 60. One and a half hours after the start of surgery, nitrous oxide was
      administered in a randomised sequence of concentrations (20, 40 and 60% end
      expired). Under steady-state conditions, mean (SD) bispectral index and spectral
      edge frequency decreased as end-tidal concentration of nitrous oxide increased,
      from 47.7 (4.3) and 15.6 (1.3) at 0% nitrous oxide to 39.8 (6.3) and 14.3 (1.8)
      at 60% nitrous oxide. A negative correlation was found between nitrous oxide
      concentration and bispectral index (r = -0.48; p < 0.01) and spectral edge
      frequency (r = -0.39; p < 0.05). We conclude that this dose-dependent decrease in
      bispectral index and spectral edge frequency induced by nitrous oxide may reflect
      the level of analgesia associated with the anaesthetic regimen.

PMID- 11576105
TI  - An audit of audit and continued educational and professional development.

PMID- 11576106
TI  - Secondary transfer of intensive care patients by helicopter.

PMID- 11576107
TI  - The unfasted elective patient.

PMID- 11576109
TI  - Anaesthesia induction rooms--sheer luxury!

PMID- 11576110
TI  - Anaesthetic machine checklists 1.

PMID- 11576112
TI  - Anaesthetic machine checklists 2.

PMID- 11576113
TI  - Checking the anaesthetic machine: a useful parallel in aviation safety.

PMID- 11576115
TI  - An uncommon cause of vaporiser failure.

PMID- 11576116
TI  - The ProSeal laryngeal mask airway.

PMID- 11576117
TI  - Airway management device (AMD).

PMID- 11576119
TI  - Short nasal tracheal tubes.

PMID- 11576121
TI  - Orthodontic appliances and insertion of the laryngeal mask airway.

PMID- 11576122
TI  - Protective effects of acidosis.

PMID- 11576124
TI  - The use of central venous cannulae in neuroanaesthesia.

PMID- 11576126
TI  - The effects of diathermy on haemodynamic stability in phaeochromocytoma.

PMID- 11576127
TI  - Pain on injection with propofol.

PMID- 11576128
TI  - Persistent cough following target-controlled infusion (TCI) with propofol.

PMID- 11576129
TI  - Unrecognised fatal anaphylactic reaction to propofol or fentanyl.

PMID- 11576131
TI  - Can propofol cause keratitis?

PMID- 11576132
TI  - Systemic spread of vecuronium following use in peribulbar regional anaesthesia.

PMID- 11576133
TI  - Huntington's chorea: use of rocuronium.

PMID- 11576134
TI  - Sevoflurane in acute intermittent porphyria.

PMID- 11576136
TI  - A sensitive anaesthetist?

PMID- 11576137
TI  - Anaesthesia in an unusual location.

PMID- 11576138
TI  - A national survey of epidural practice.

PMID- 11576139
TI  - Combinations of opioids for epidural analgesia.

PMID- 11576140
TI  - Misconnection misadventure.

PMID- 11576141
TI  - Luer-lock epidural connections.

PMID- 11576143
TI  - Paraesthesia during spinal needle placement.

PMID- 11576142
TI  - Hip flexion for lumbar puncture--not easy in obstetric practice.

PMID- 11576144
TI  - Abdominal field block: a new approach via the lumbar triangle.

PMID- 11576145
TI  - EMLA or Ametop, and for how long?

PMID- 11576146
TI  - EMLA--1 h is not enough for venous cannulation.

PMID- 11576147
TI  - Unexpected benefit from 'recovery' positioning.

PMID- 11576148
TI  - A risk associated with the shared airway in reconstructive palate surgery.

PMID- 11576149
TI  - Pre-oxygenation: silence the flush.

PMID- 11576150
TI  - Paternal pulse oximetry.

PMID- 11576151
TI  - Effects of pharmacological adrenergic and vagal modulation on fractal heart rate
      dynamics.
AB  - Breakdown of short-term fractal-like behaviour of HR indicates an increased risk
      for adverse cardiovascular events and mortality, but the pathophysiological
      background for altered fractal HR dynamics is not known. Our aim was to study the
      effects of pharmacological modulation of autonomic function on fractal
      correlation properties of heart rate (HR) variability in healthy subjects. Short
      term fractal scaling exponent (alpha1) along with spectral components of HR
      variability were analysed during the following pharmacological interventions in
      healthy subjects: (i) noradrenaline (NE) infusion (n=22), (ii) NE infusion after
      phentolamine (PHE) (n=8), (iii) combined NE + adrenaline (EPI) infusion (n=12),
      (iv) vagal blockade with high dose of atropine (n=10), (v) and vagal activation
      by low dose of atropine (n=10). Then alpha1 decreased progressively during the
      incremental doses of NE (from 0.85 +/- 0.250 to 0.55 +/- 0.23, P<0.0001). NE also
      decreased the average HR (P<0.001) and increased the high frequency spectral
      power (P<0.001). Vagal blockade with atropine increased the alpha1 value (from
      0.82 +/- 0.22 to 1.24 +/- 0.41, P<0.05). Combined NE + EPI infusion and vagal
      activation with a low dose atropine did not result in any changes in alpha1, and
      alpha-adrenergic blockade by PHE did not completely reverse the effects of NE on
      alpha1. Increased levels of circulating NE result in reduction of short-term
      correlation properties of HR dynamics. The results suggest that coactivation of
      cardiac vagal outflow at the time of high levels of a circulating sympathetic
      transmitter explains the breakdown of fractal-like behaviour of human HR
      dynamics.

PMID- 11576152
TI  - Forearm blood flow measurements using computerized R-wave triggered strain-gauge
      venous occlusion plethysmography: unilateral vs. bilateral measurements.
AB  - The human forearm is a well established model to study local vascular reactivity
      in humans in vivo, using strain-gauge venous occlusion plethysmography to measure
      blood flow and changes in blood flow in the forearm. To reduce the intra
      individual variability of the forearm blood flow (FBF), it has been advocated
      that simultaneous measurements of contralateral forearm blood flow is obligatory.
      Therefore, the use of the calculated forearm ratio (FR) is recommended instead of
      using the actual FBF. In the present study we compared the intra-individual
      variability of forearm blood flow measurements and the forearm ratio, by using
      computerized R-wave triggered strain-gauge venous occlusion plethysmography, to
      test if bilateral expression of measurements is better than unilateral. Results
      were obtained in eight volunteers. Intra-arterial infused sodium nitroprusside
      induced a dose dependent increase in forearm blood flow and a dose dependent
      increase in the calculated forearm ratio. Intra-arterial infused norepinephrine
      induced a dose dependent decrease in forearm blood flow and a dose dependent
      decrease in the calculated forearm ratio. The differences between the variation
      coefficients of the forearm blood flow measurements and the calculated forearm
      ratio were different. These results support our hypothesis that by using a
      computerized, R-wave triggered system for unilateral forearm blood flow
      measurement is a more reliable outcome than the calculated forearm ratio derived
      from bilateral measurements.

PMID- 11576153
TI  - Effects of caffeine and high ambient temperature on haemodynamic and body
      temperature responses to dynamic exercise.
AB  - Caffeine can enhance mean arterial blood pressure (MAP) and attenuate forearm
      blood flow (FBF) and forearm vascular conductance (FVC) during exercise in
      thermal neutral conditions without altering body temperature. During exercise at
      higher ambient temperatures, where a greater transfer of heat from the body core
      to skin would be expected, caffeine-induced attenuation of FBF (i.e. cutaneous
      blood flow) could attenuate heat dissipation and increase body temperature
      (T(re)). We hypothesized that during exercise at an ambient temperature of 38
      degrees C, caffeine increases MAP, and attenuates FBF and FVC such that T(re) is
      increased. Eleven caffeine-naive, active men, were studied at rest and during
      exercise after ingestion of a placebo or 6 mg kg(-1) of caffeine. MAP, heart rate
      (HR), FBF, FVC, T(re) skin temperature (T(sk)) and venous lactate concentrations
      (lactate) were assessed sequentially during rest at room temperature, after 45
      min of exposure to an ambient temperature of 38 degrees C, and during 35 min of
      submaximal cycling. Heat exposure caused increases in MAP, FBF, FVC and T(sk)
      that were not altered by caffeine. HR, T(re), and lactate were unaffected. During
      exercise, only MAP (95 +/- 2 vs. 102 +/- 2 mmHg), HR (155 +/- 10 vs. 165 +/- 10
      beats min(-1)), and lactate (2.0 +/- 0.4 vs. 2.3 +/- 0.4 mmol l(-1)) were
      increased by caffeine. These data indicate that increases in cutaneous blood flow
      during exercise in the heat are not reduced by caffeine. This may be because of
      activation of thermal reflexes that cause cutaneous vasodilation capable of
      offsetting caffeine-induced reductions in blood flow. Caffeine-induced increases
      in lactate, MAP and HR during exercise suggest that this drug and high ambient
      temperatures increase production of muscle metabolites that cause reflex
      cardiovascular responses.

PMID- 11576154
TI  - Atrioventricular conduction: a determinant for the manifestation of ventricular
      preexcitation in patients with Wolff-Parkinson-White syndrome.
AB  - The relation between the atrioventricular conduction properties of the
      atrioventricular node and the anterograde conduction ability over the accessory
      pathway in the Wolff-Parkinson-White syndrome has never been studied.
      Atrioventricular nodal characteristics were studied in 285 patients with manifest
      and 204 with concealed accessory pathway who underwent radiofrequency ablation,
      and compared with 146 controls. First and second degree atrioventricular block
      was observed in 13 (5%) preexcitation patients after ablation, compared with none
      in concealed accessory pathway (P=0.001) and control patients (P=0.006). The
      atrial-His intervals in preexcitation patients (88 +/- 20 ms) was significantly
      longer than in concealed accessory pathway (76 +/- 15 ms, P<0.0001) and control
      patients (77 +/- 15 ms, P=0.0007), as was PR intervals (165 +/- 25 versus 149 +/-
      20 and 150 +/- 21 ms, P<0.0001, respectively) even after excluding those with
      atrioventricular block. Significant differences in PR and atrial-His intervals
      were not observed between concealed accessory pathway and control patients. More
      preexcitation patients had ventriculoatrial dissociation than had patients in the
      other groups. The results indicate that atrioventricular block is not uncommon in
      preexcitation patients and a relatively long atrioventricular conduction time is
      an electrophysiological prerequisite for the manifestation of preexcitation in
      the Wolff-Parkinson-White syndrome.

PMID- 11576155
TI  - A new method to quantify postexercise ST-deviation--the ST-deficit. A study in
      men at high and low-risk for coronary heart disease.
AB  - BACKGROUND: Quantitative heart rate adjusted exercise ST criteria like
      microV/beats per minute (bpm) improve the diagnostic accuracy of the exercise
      ECG. However, there are few quantitative HR adjusted postexercise variables
      available. The aim of the present exercise study was to evaluate a new such
      variable from computerized averaging of the postexercise ECG. METHODS: The
      presence of possible myocardial ischaemia in a population based sample of 74
      elderly male hypertensives at high-risk of coronary heart disease, and in 42 age
      matched clinically healthy males (reference group) at low-risk was assessed by
      exercise ECG. All men had a normal resting ECG without signs of ischaemia.
      VARIABLES STUDIED: standard ST-criteria, ST/HR slope < or =-2.4 microV. bpm-1,
      shape of the rate-recovery loop, the latter also with a new quantitative
      variable, the ST-deficit. RESULTS: In spite of a normal resting ECG many subjects
      showed an abnormal ST/HR slope during exercise, 43% in the hypertension group and
      26% in the reference group. An abnormal rate-recovery loop (ST-deficit) also
      contributed substantially to identify patients with possible myocardial
      ischaemia, 30 vs. 10%, respectively (P<0.02); cumulatively for the two HR
      adjusted criteria 53% vs. 29%, respectively (P<0.02). Mean ST-deficit was
      significantly lower in the high-risk group. CONCLUSIONS: Effort-related
      myocardial ischaemia is frequently silent in elderly high-risk hypertensives and
      necessitates testing, preferably with computerized exercise ECG and heart rate
      adjusted ST criteria. A new quantitative variable to assess the postexercise rate
      recovery loop in the time domain, the ST-deficit is described. This variable
      seems to effectively discriminate between subjects with low and high-risk for
      coronary heart disease and thus provides new information. Further studies are
      warranted to validate this variable against myocardial perfusion scintigraphy and
      coronary angiography.

PMID- 11576156
TI  - Interindividual variability of surface EMG changes during cycling exercise in
      healthy humans.
AB  - We studied surface electromyogram (SEMG) changes during 1-h endurance cycling in
      12 healthy subjects of whom five were involved in mountain bike training
      programme. The work load was set at 50% of the predicted maximal heart rate. The
      surface EMG and the compound evoked muscle action potential (M-wave) from the
      vastus lateralis muscle were recorded at rest, during the 1-h cycling period, and
      the 20-min recovery period. The root mean square (RMS) and the median frequency
      (MF) of SEMG power spectrum were computed. In all subjects, there was no shift in
      the median frequency throughout the cycling period and the increase in RMS
      remained stable. In subjects untrained to endurance cyclism, the M-wave duration
      increased at the end of the cycling period and these changes persisted for a
      consecutive 15-min period during recovery of exercise. By contrast, in trained
      mountain bikers the M-wave duration decreased after 2 min of exercise--the effect
      persisting for 2 min during recovery. These data suggest that the interpretation
      of M-wave changes during cycling must take into consideration the sport practices
      of the subjects and also that SEMG power spectrum and M-wave explore different
      electrophysiological events.

PMID- 11576157
TI  - Computerized analysing system using the active contour in ultrasound measurement
      of carotid artery intima-media thickness.
AB  - BACKGROUND AND PURPOSE: B-mode measurement of the carotid intima-media (IM)
      thickness (T) based on manual tracing (MT) procedures are dependent on the
      subjectivity of the reader and the existing automatic tracing procedures often
      fail to detect the IM boundaries accurately. The purpose of this study was to
      compare the tracing results of the IM boundaries of the carotid wall with a new
      automatic identification (AI) procedure, based on an active contour model, and
      computer-assisted manual tracing (MT). METHODS: The detection of the IM
      boundaries was performed with both procedures in 126 ultrasound images [63 each
      of the common carotid artery (CCA) and carotid bulb] along the far wall of the
      distal CCA and the carotid bulb. Intra- and inter-reader variability for mean and
      maximum IMT with AI and MT and accuracy of identification of both IM boundaries
      were evaluated. RESULTS: Using MT the intra- and inter-reader variability
      amounted to 0.01-0.03 and 0.03-0.07 mm, respectively. The variability was
      slightly higher in the carotid bulb than in the CCA. Using AI the variability was
      almost eliminated. Mean and maximum IMT were measured systematically lower by AI
      compared with MT in all regions by 0.01 mm. The accuracy of identification was
      similar for both IM boundaries, but lower in the carotid bulb region than in the
      CCA. CONCLUSIONS: The new AI procedure identifies both IM boundaries in the
      region of the far wall of the CCA and carotid bulb with high precision, and
      eliminates most of the intra- and inter-reader variability of the IMT measurement
      using MT.

PMID- 11576158
TI  - Effect of local cold provocation on systolic blood pressure and skin blood flow
      in the finger.
AB  - Demonstration of increased vascular cold reactivity in patients with Raynaud's
      syndrome is difficult. For medico-legal reasons, it is important to get objective
      measures of vasospasm in these patients. Evaluation of the degree of vasospasm
      also provides prognostic information which is useful for patient management. In
      this study, we compare two methods of arterial circulation measurement. The laser
      Doppler scanning is a new method, which uses the recently developed laser Doppler
      perfusion imaging (LDPI) instrument. The aim of the present study was to compare
      the effect on finger skin blood flow measured with LDPI with changes in finger
      systolic blood pressure during local cold provocation. The effect of such
      provocation, skin blood flow and systolic blood pressure, were studied in 15
      healthy controls. Six patients with known traumatic vasospastic disease (TVD)
      were also tested with both methods. Finger skin blood flow was measured with LDPI
      on the distal phalanx of the index finger of the left hand, every minutes during
      6 min of local heating at 40 degrees C followed by local cooling for 3 min at 15
      degrees C and then for 3 min at 10 degrees C. Finger systolic blood pressure was
      measured with strain-gauge method before and after local cooling to 10 degrees C
      with a cuff perfused with water of desired temperature. The test was performed in
      the same finger within a week of the laser Doppler scanning. Local finger cooling
      to 15 degrees C and 10 degrees C caused a significant decrease in blood flow,
      most marked at 10 degrees C. There was, however, no correlation between the
      decrease in blood flow and blood pressure. In the TVD-patients decreases in skin
      blood flow were similar compared with the healthy controls. In contrast, the
      changes in systolic blood pressure, were outside normal range (systolic quotient
      <0.65) in five of the six patients (83%), and also in 11 of the 15 healthy
      controls (73%). In conclusion, there is no correlation between the decrease in
      finger skin blood flow and systolic blood pressure during local cold provocation.
      For diagnosis of traumatic vasospastic disease (TVD), local cold-induced changes
      in finger systolic blood pressure seems superior to changes in skin blood flow,
      but the ideal clinical method for demonstrating increased cold-induced vasospasm
      is, however, still lacking.

PMID- 11576159
TI  - High-frequency components in ECG analysed in guinea-pig Langendorf preparations.
AB  - High-frequency components in ECG during global ischaemia were studied in isolated
      guinea-pig hearts perfused ad modum Langendorf. Electrocardiograph recordings
      were carried out from the epicardial surface both in normo- and low-flow
      perfusion. After bandpass filtering (5-500 Hz), signal-averaging, was undertaken.
      The high-frequency components either increased or decreased after low-flow
      perfusion was instituted. Root-mean-square voltage (RMS) of the depolarization
      signal correlated poorly with the signal amplitude, but highly with the first and
      second derivative, i.e. the velocity and the acceleration of the signal. It is
      concluded that high-frequency components are not pathological phenomena per se,
      but reflect the shape of the original electrocardiographic signal.

PMID- 11576160
TI  - Ventilation-perfusion inequality and carbon dioxide sensitivity in hypoxaemic
      chronic obstructive pulmonary disease (COPD) and effects of 6 months of long-term
      oxygen treatment (LTOT).
AB  - The aim of our study was to find out how blood gas disturbances in stable,
      eucapnic, severe chronic obstructive pulmonary disease (COPD) patients with an
      arterial oxygen tension (PaO(2)) value of 7.7 (6.1-8.4) kPa are affected by
      ventilation-perfusion (V(A)/Q) relationships and carbon dioxide (CO(2))
      sensitivity and how these parameters are influenced by 6 months of long-term
      oxygen treatment (LTOT). V(A)/Q ratios were measured using the multiple inert gas
      elimination technique (MIGET). Mouth occlusion pressure 0.1 s after onset of
      inspiration (Pi0.1) and minute ventilation (V(E)) were measured to assess
      respiratory drive response (DeltaPi0.1/DeltaPCO(2)) and hypercapnic ventilatory
      response (HCVR) to CO(2) rebreathing. At the start of LTOT, a normal median
      respiratory drive response level of 1.2 (0.2-2.3) cm H2O/kPa and a low median
      HCVR as compared with healthy individuals (P<0.001) were found. However, 7.9 (0
      29.8)% of the VE, was directed towards hypoperfused lung areas. The dispersion of
      ventilation (log SDV; 0.47-1.76), and the dispersion of perfusion (log SDQ; 0.66
      1.07) were wider than normal. The PaO(2) level correlated inversely with mean
      V(A)/Q ratio for ventilation (V mean) and shunt. The PaCO(2) level correlated
      inversely with HCVR and vital capacity. After 6 months of LTOT, no significant
      changes in daytime blood gas levels, CO(2)-sensitivity or VA/Q ratios were found.
      VE tended to be reduced by 1.0 l min-1. CONCLUSIONS: An elevated V mean and
      probably shunting are important contributing factors for the reduced PaO(2) and
      hypercapnic ventilatory response is a major determinant of PaCO(2) in eucapnic
      stable hypoxaemic COPD. Six months of LTOT does not affect blood gases, CO(2)
      sensitivity or ventilation-perfusion relationships.

PMID- 11576161
TI  - Heart rate variability and its determinants in patients with severe or mild
      essential hypertension.
AB  - How cardiac autonomic nervous control is related to the severity of essential
      hypertension in patients receiving long-term antihypertensive therapy is not well
      known. The aim of this study was to examine heart rate variability (HRV), a non
      invasive measure of cardiac autonomic function, in patients with long-term and
      medically treated mild and severe essential hypertension and healthy control
      subjects, and to assess the clinical determinants of HRV in these patients.
      Thirty-four patients with severe essential hypertension (SEHT) and 29 with mild
      essential hypertension (MEHT) as well as healthy age- and sex-matched control
      subjects were studied. HRV was assessed from 10 min ECG-recordings during paced
      (0.2 Hz) breathing at rest and expressed as time and frequency domain measures.
      In the SEHT group time (SDNN, RMSSD) and frequency domain measures (total power,
      low-frequency (LF) power and high-frequency (HF) power of HRV in absolute units,
      and LF and HF power of HRV in normalized units) of HRV were significantly lower
      when compared with those of the control group. The MEHT and control groups did
      not differ from each other with respect to time or frequency domain measures of
      HRV. Comparison between the hypertensive groups showed that SDNN, total power, LF
      power and HF power were lower in the SEHT group compared with the MEHT group
      (P<0.05 for all). Among hypertensive patients RR-interval, age, gender, systolic
      finger blood pressure and diastolic office blood pressure as well as 24-h blood
      pressure were significant determinants of HRV. In conclusion, we found that the
      severity of chronic essential hypertension seems to be related to the severity of
      impairment of cardiac autonomic control.

PMID- 11576162
TI  - Effects of resistance training on cardiovascular responses to lower body negative
      pressure in the elderly.
AB  - The purpose of the present study was to determine whether resistance training
      alters the cardiovascular responses to submaximal lower body negative pressure
      (LBNP) in the elderly. Twenty-one subjects were randomized into a control (C:
      n=10; 70 +/- 3 years, mean +/- SD) or a resistance training (TR: n=11; 67 +/- 7
      years) group. Subjects in the TR underwent 12 weeks of training consisting of
      three sets of 8-12 contractions at approximately 60-80% of their initial maximal
      one repetition, three times per week, on 10 different machines. Before (Pre) and
      after (Post) training, all subjects underwent exposures of LBNP of -10, -20 and 
      40 Torr and muscle biopsy sampling at the vastus lateralis. TR increased (P< or
      =0.05) knee extension (Pre=379 +/- 140 N, Post=534 +/- 182 N) and chest press
      (Pre=349 +/- 137 N, Post=480 +/- 192 N) strength. Neither body weight nor
      percentage body fat were altered (P >0.05) by training. Resistance training
      increased (P< or =0.05) cross-sectional area in both Type I (4203 +/- 1196 to
      5248 +/- 1728 microm2) and Type II (3375 +/- 1027 to 4286 +/- 1892 microm2)
      muscle fibres. Forearm blood flow, forearm vascular conductance, mean arterial
      pressure, and heart-rate responses to LBNP were not altered by the training.
      These data suggest that the cardiovascular responses of elderly to LBNP are
      unaffected by 12 weeks of whole-body resistance training despite increases in
      muscle strength and size.

PMID- 11576163
TI  - Human G protein beta3 subunit variant does not alter hypercarbic or hypoxic
      ventilatory response.
AB  - Hypercarbic respiratory drive is mainly determined by PCO(2) and pH with activity
      of the intracellular Na+/H+ exchanger (NHE) playing an important role in
      maintaining intracellular pH and respiratory drive. Because NHE activity varies
      with genetically different G-protein beta3 subunits (GNB3) (C/T polymorphism at
      nucleotide position 825) different genotypes might alter respiratory regulation.
      To test the hypothesis that short-term ventilatory responses vary with different
      GNB3 healthy volunteers with different genotypes (CC, TC, TT) were exposed to
      either hyperoxic hypercarbia (n=33) or to isocapnic hypoxia (n=31), respectively.
      There was no difference between CC, TC, and TT genotypes in hypercarbic and
      hypoxic respiratory drive when assessed as the ratio of minute ventilation over
      endexpiratory PCO(2) changes (DeltaV.E/DeltaPETCO(2)), maximal tolerable
      PETCO(2), and ratio of changes in ventilation over arterial haemoglobin
      desaturation (DeltaV.E/DeltaSO(2)), respectively. Thus, short-term hypercarbic
      and hypoxic ventilatory drive do not differ between individuals with genotypes
      encoding different GNB3. Whilst respiratory control may still be influenced by G
      protein aberration, other mechanisms seem to have a more important role in
      controlling ventilation.

PMID- 11576164
TI  - Atrioventricular plane displacement correlates closely to circulatory dimensions
      but not to ejection fraction in normal young subjects.
AB  - AIMS: Mitral atrioventricular plane displacement (AVPD) provides information
      about left ventricular systolic function. M-mode of systolic annulus amplitude or
      tissue Doppler imaging of systolic annulus velocity are the current methods of
      evaluating AVPD. A correlation to ejection fraction (EF) has been demonstrated in
      patients with coronary artery disease and left ventricular dysfunction. Our aim
      was (i) to investigate the mitral AVPD of normal subjects with different physical
      work capacities and (ii) to further evaluate AVPD as an index of left ventricular
      systolic function. METHODS AND RESULTS: Twenty-eight healthy men mean age 28
      years (20-39) were included: endurance trained (ET) (n=10), strength trained (ST)
      (n=9) and untrained (UT) (n=9). The systolic AVPD was recorded at four sites,
      septal, lateral, anterior and posterior, using M-mode. Left ventricular volumes
      were calculated according to Simpson's rule. Systolic AVPD was higher in
      endurance trained, 16.9 +/- 1.5 mm, as compared with both strength trained, 13 +/
      1.6 (P<0.001) and untrained, 14 +/- 1.6 (P<0.001). Left ventricular systolic
      AVPD correlated strongly with end-diastolic volume (r=0.82), stroke volume
      (r=0.80) and maximal oxygen consumption per body weight (r=0.72). The correlation
      between AVPD and EF was poor (r=0.22). CONCLUSION: In the subjects studied, with
      a range of normal cardiac dimensions, AVPD correlated to stroke volume, end
      diastolic volume and maximal oxygen consumption per body weight, but not to EF.
      On theoretical grounds, it also seems reasonable that a dimension like AVPD is
      related to other cardiac dimensions and volumes, rather than to a fraction, like
      EF. AVPD is one parameter that is useful for evaluation of left ventricular
      systolic function but is not interchangeable with other measurements such as EF.

PMID- 11576165
TI  - Standardized submaximal exercise testing in never smokers: a normative study.
AB  - In a population survey on the south-western coast of Norway, 373 never smokers
      aged 18-73 years (230 women) without respiratory symptoms performed a
      standardized, progressive, incremental submaximal bicycle exercise test. All
      individuals were able to do an exercise involving oxygen uptake of 1.0 l min(-1),
      80% of the subjects reached 1.5 l min(-1) and 50% of the subjects reached 2.0 l
      min(-1). The respiratory frequency (RF), ventilation (VE) and heart rate (HR) for
      a given oxygen uptake were all higher in women than in men. Significant
      predictors of failure to reach oxygen uptake of 1.5 and 2.0 l min(-1) were sex,
      age, body height and weight. Prediction equations are given for respiratory
      frequency, heart rate and ventilation for an oxygen uptake of 1.0 l min(-1) in
      women and 1.5 l min(-1) in men; and body height is a strong predictor for all
      dependent variables. A multiple linear regression analysis in women showed that
      age was a significant predictor of respiratory frequency (P<0.05), ventilation
      (P<0.001) and heart rate (P<0.001), while in men age was a significant predictor
      only of ventilation (P<0.001) during the bicycle exercise protocol.

PMID- 11576166
TI  - Pluripotent cells (stem cells) and their determination and differentiation in
      early vertebrate embryogenesis.
AB  - Mammalian embryonic stem cells can be obtained from the inner cell mass of
      blastocysts or from primordial germ cells. These stem cells are pluripotent and
      can develop into all three germ cell layers of the embryo. Somatic mammalian stem
      cells, derived from adult or fetal tissues, are more restricted in their
      developmental potency. Amphibian ectodermal and endodermal cells lose their
      pluripotency at the early gastrula stage. The dorsal mesoderm of the marginal
      zone is determined before the mid-blastula transition by factors located after
      cortical rotation in the marginal zone, without induction by the endoderm.
      Secreted maternal factors (BMP, FGF and activins), maternal receptors and
      maternal nuclear factors (beta-catenin, Smad and Fast proteins), which form
      multiprotein transcriptional complexes, act together to initiate pattern
      formation. Following mid-blastula transition in Xenopus laevis (Daudin) embryos,
      secreted nodal-related (Xnr) factors become important for endoderm and mesoderm
      differentiation to maintain and enhance mesoderm induction. Endoderm can be
      induced by high concentrations of activin (vegetalizing factor) or nodal-related
      factors, especially Xnr5 and Xnr6, which depend on Wnt/beta-catenin signaling and
      on VegT, a vegetal maternal transcription factor. Together, these and other
      factors regulate the equilibrium between endoderm and mesoderm development. Many
      genes are activated and/or repressed by more than one signaling pathway and by
      regulatory loops to refine the tuning of gene expression. The nodal related
      factors, BMP, activins and Vg1 belong to the TGF-beta superfamily. The
      homeogenetic neural induction by the neural plate probably reinforces neural
      induction and differentiation. Medical and ethical problems of future stem cell
      therapy are briefly discussed.

PMID- 11576167
TI  - Multiple personalities: synaptic target cells as introverts and extroverts.
AB  - The intricate process of wiring a neuronetwork requires a high degree of accuracy
      in the communication between pre- and post-synaptic cells. While presynaptic
      cells have been widely recognized for their dynamic role in synaptic matchmaking,
      post-synaptic cells have historically been overlooked as passive targets. Recent
      studies in the Drosophila embryonic neuromuscular system provide compelling
      evidence that post-synaptic cells participate actively in the synaptogenic
      process. Endocytosis allows them to quickly modify the array of molecular cues
      they provide on their surfaces and the extension of dynamic filopodia allows post
      synaptic cells to engage in direct long-distance communication. By making use of
      familiar cellular mechanisms such as endocytosis and filopodia formation, post
      synaptic cells may be able to communicate more effectively with potential
      synaptic partners.

PMID- 11576168
TI  - Origin and evolution of the neural crest: a hypothetical reconstruction of its
      evolutionary history.
AB  - The neural crest has long been regarded as one of the key novelties in vertebrate
      evolutionary history. Indeed, the vertebrate characteristic of a finely patterned
      craniofacial structure is intimately related to the neural crest. It has been
      thought that protochordates lacked neural crest counterparts. However, recent
      identification and characterization of protochordate genes such as Pax3/7, Dlx
      and BMP family members challenge this idea, because their expression patterns
      suggest remarkable similarity between the vertebrate neural crest and the
      ascidian dorsal midline epidermis, which gives rise to both epidermal cells and
      sensory neurons. The present paper proposes that the neural crest is not a novel
      vertebrate cell population, but may have originated from the protochordate dorsal
      midline epidermis. Therefore, the evolution of the vertebrate neural crest should
      be reconsidered in terms of new cell properties such as pluripotency,
      delamination-migration and the carriage of an anteroposterior positional value,
      key innovations leading to development of the complex craniofacial structure in
      vertebrates. Molecular evolutionary events involved in the acquisitions of these
      new cell properties are also discussed. Genome duplications during early
      vertebrate evolution may have played an important role in allowing delamination
      of the neural crest cells. The new regulatory mechanism of Hox genes in the
      neural crest is postulated to have developed through the acquisition of new roles
      by coactivators involved in retinoic acid signaling.

PMID- 11576169
TI  - Role of the FGF and MEK signaling pathway in the ascidian embryo.
AB  - In the ascidian embryo, a fibroblast growth factor (FGF)-like signal from
      presumptive endoderm blastomeres between the 32-cell and early 64-cell stages
      induces the formation of notochord and mesenchyme cells. However, it has not been
      known whether endogenous FGF signaling is involved in the process. Here it is
      shown that 64-cell embryos exhibit a marked increase in endogenous extracellular
      signal-regulated kinase (ERK/MAPK) activity. The increase in ERK activity was
      reduced by treatment with an FGF receptor 1 inhibitor, SU5402, and a MEK (ERK
      kinase/MAPKK) inhibitor, U0126. Both drugs blocked the formation of notochord and
      mesenchyme when embryos were treated at the 32-cell stage, but not at the 2- or
      110-cell stages. The dominant-negative form of Ras also suppressed notochord and
      mesenchyme formation. Both inhibitors suppressed induction by exogenous basic
      FGF. These results suggest that the FGF signaling cascade is indeed necessary for
      the formation of notochord and mesenchyme cells during ascidian embryogenesis. It
      is also shown that FGF signaling is required for formation of the secondary
      notochord, secondary muscle and neural tissues, and at least ERK activity is
      necessary for the formation of trunk lateral cells and posterior endoderm.
      Therefore, FGF and MEK signaling are required for the formation of various
      tissues in the ascidian embryo.

PMID- 11576170
TI  - Changes in adhesive properties of epithelial cells during early morphogenesis of
      the mammary gland.
AB  - Previous studies have demonstrated that cell adhesion systems are downregulated
      in epithelial buds at the earliest stages of submandibular gland and hair
      follicle development, but are restored at subsequent stages. Here it is shown
      that epithelial cell adhesion systems are also remodeled during early mammary
      gland development. Immunofluorescence and electron microscopy of the mouse
      mammary bud demonstrated that cell-cell adhesion systems were hardly detectable,
      with significant downregulation of expression of desmosomal molecules, but not of
      E-cadherin and beta-catenin. Hemidesmosomal structures were also rarely found,
      although their component molecules were expressed. Differences in cell adhesivity
      between cells of the mammary bud and those of the overlying epidermis were shown
      by the finding that the mammary cells formed smaller aggregates than the
      epidermal cells and were not randomly mixed with the epidermal cells. At
      subsequent stages, the mammary epithelium restored cell-cell adhesion systems
      along with de novo expression of tight junction molecules. These data, together
      with previous findings, indicate that remodeling of epithelial cell adhesion
      systems is a general feature underlying the early development of several ectoderm
      derived organs and support the idea that segregation and rearrangements of cells
      are involved in early epithelial morphogenesis.

PMID- 11576171
TI  - Maternal Nanos and Pumilio regulate zygotic vasa expression autonomously in the
      germ-line progenitors of Drosophila melanogaster embryos.
AB  - vasa (vas) is transcribed earliest among reported genes expressed in the germ
      line progenitors, or pole cells, in Drosophila melanogaster embryos. Its
      expression is detected in the germ-line cells throughout their development,
      making vas expression a useful marker for the establishment of germ-line fate. In
      the present report, it is shown that maternal Nos and Pum are required for normal
      expression of vas in pole cells. First, expression of enhancer-trap marker BC69,
      which reflects vas expression, is promoted by maternal Nos and Pum. Second,
      expression of vas mRNA in pole cells is promoted by maternal Nos and Pum. Third,
      pole cell transplantation experiments reveal that maternal Nos and Pum are
      required autonomously in pole cells for proper expression of vas. Finally, Nos
      and Pum are dispensable for vas expression in oogenesis, although they are
      expressed zygotically in adult ovaries. These observations show that germ-line
      specific vas expression is promoted by autonomous function of maternal Nos and
      Pum in the germ-line progenitors during embryogenesis, and is regulated
      differentially in embryogenesis and oogenesis.

PMID- 11576172
TI  - Upregulation of cellular retinoic acid-binding protein I expression by ethanol.
AB  - Acute and chronic ethanol ingestion cause embryopathy similar to that of hyper-
      or hypovitaminosis A. Experimental data have suggested interaction between
      vitamin A and alcohol signaling pathways at the level of metabolic interference,
      which ultimately affects the concentration of retinoic acid (RA) in animals. The
      present study was set up to examine the possible effects of alcohol on cellular
      RA binding protein I (CRABP-I) expression during embryonic development by using
      transgenic mouse embryos and P19 embryonal carcinoma cells as experimental
      models. It was found that expression of the mouse CRABP-I gene was elevated in
      developing embryos at mid-gestation stages as a result of ethanol consumption by
      the mothers. Specific elevation of this gene was detected in the limb bud and the
      gut. In the P19 model, the CRABP-I gene was directly upregulated by ethanol,
      which was not blocked by a protein synthesis inhibitor. Furthermore, the
      regulation of the CRABP-I gene by ethanol was mediated by the 5' upstream
      regulatory region of the CRABP-I gene promoter. A potential interaction of
      vitamin A and ethanol at the level of CRABP-I gene expression is discussed.

PMID- 11576173
TI  - XCL-2 is a novel m-type calpain and disrupts morphogenetic movements during
      embryogenesis in Xenopus laevis.
AB  - We identified a novel cDNA, XCL-2, encoding an m-type calpain, a calcium
      dependent intracellular protease. This protein has all characteristic structures
      and active sites of canonical calpains. Zygotic transcription of the gene was
      first detected at stage 10. It is expressed exclusively in the ventral
      circumblastoporal collar and the mesoderm-free zone at the most anterior tip of
      neural fold in late gastrulae and neurulae. In later stages, expression is only
      found in cement gland and proctodeum. It is also expressed in a tissue-specific
      manner. In adult tissues, various levels of expression were detected in brain,
      eye, heart, intestine, kidney, lung, stomach and testis, but not in liver,
      muscle, nerve, ovary, skin and spleen. Overexpression of wild-type XCL-2 suggests
      that this gene is involved in gastrulation movement and convergent extension
      during gastrulation and neurulation. Overexpression of a dominant-negative mutant
      caused a phenotype morphologically similar to, but histologically different from,
      that caused by overexpression of wild-type XCL-2. The mutant phenotype can be
      rescued by injection of wild-type XCL-2. These data suggest that XCL-2 plays an
      important role in convergent extension movements during embryogenesis in Xenopus
      laevis.

PMID- 11576174
TI  - Ascidian Wnt-5 gene is involved in the morphogenetic movement of notochord cells.
AB  - Wnt proteins play important roles in many developmental events. Wnts are divided
      into two groups according to biological function. The Wnt-5a class proteins
      function in morphogenetic movement during embryogenesis. Previously, a Wnt-5
      homolog has been isolated from the ascidian, Halocynthia roretzi. HrWnt-5 is
      expressed in the notochord until the tail-bud stage, implying a role in the
      notochord. In this study, the function of HrWnt-5 was investigated. When HrWnt-5
      mRNA was injected into fertilized eggs, the embryos showed morphologic defects at
      around the neurula stage. The anterior-posterior axis was shorter than in control
      embryos. These defects were caused by the abnormal movement of notochord cells.
      However, the overexpression of HrWnt-5 mRNA did not affect the differentiation of
      tissues, suggesting that HrWnt-5 solely regulates the morphogenetic movement.
      Although endogenous HrWnt-5 is expressed in the notochord, the overexpression of
      HrWnt-5 mRNA caused the defects, suggesting that the amount of HrWnt-5 mRNA in
      the notochord is strictly regulated. These results suggest that HrWnt-5 regulates
      the morphogenetic movement of notochord cells during ascidian embryogenesis.

PMID- 11576175
TI  - Myb-binding site regulates the expression of glucosamine-6-phosphate isomerase in
      Dictyostelium discoideum.
AB  - A homolog of the glucosamine-6-phosphate isomerase in the cellular slime mold
      Dictyostelium discoideum has been analyzed. The gene disruption mutant was
      arrested at the mound stage, demonstrating that the gene is important for
      development. The gene was expressed in vegetatively growing cells, silenced on
      starvation and expressed again in prestalk cells during the multicellular stages.
      The upstream region of the gene (1376 bp relative to ATG) was cloned and
      sequenced to study the transcription control mechanisms. Analysis of deletion
      mutants and a site-directed mutant indicated that the Myb-binding sequence (5'
      AACTG-3') localized in the upstream region is important for gene expression. The
      results of gel-shift assays showed the presence of an Myb-related protein binding
      to the sequence at the growing phase and another protein binding to the sequence
      at developmental stages.

PMID- 11576176
TI  - Analysis of haploid development based on expression patterns of developmental
      genes in the medaka Oryzias latipes.
AB  - The abnormalities of haploid medaka embryos were characterized by comparative
      analysis of histologic sections and expression patterns of some developmental
      marker genes between haploids and diploids to clarify whether medaka haploids are
      useful for identifying mutants. During gastrulation, an obvious defect was first
      observed as a delay of epiboly and involution. This delay was shown to be caused
      not by the perturbation of mesoderm induction, but by widespread cell death and
      disorganization of cell arrangement in the blastoderm. This disorganization of
      cell arrangement was also detected in various organs, such as the brain, somite
      and notochord, at a late developmental stage. Ten days after fertilization, a
      small head and a short body axis were formed; these changes were also observed in
      haploid embryos in other species, but their cause is unknown. Based on the
      expression patterns of HNF3beta and goosecoid, it was demonstrated that a short
      and impotent prechordal plate induced near the marginal zone in haploid embryos
      was responsible for this defect. However, in these experiments it was also
      demonstrated that many major organs in haploids, such as the somite and
      notochord, differentiated incompletely but were present. Therefore, it was
      concluded that haploid screening is suitable for identifying mutations revealed
      by an obvious phenotype, such as dorsoventral polarity.

PMID- 11576177
TI  - An RGDS peptide-binding receptor, FR-1R, localizes to the basal side of the
      ectoderm and to primary mesenchyme cells in sand dollar embryos.
AB  - Immunoblotting using polyclonal antibodies (pAb) raised against an FR-1 receptor
      (FR-1R), a 57 kDa Arg-Gly-Asp-Ser (RGDS)-binding protein, of the sand dollar
      Clypeaster japonicus showed that the pAb monospecifically bound to the protein.
      FR-1R was present in purified plasma membrane, suggesting that the protein is a
      membrane-bound protein. The molecular structure of FR-1R did not change
      throughout the early embryogenesis, whereas its expression changed significantly
      during this period. FR-1R was present in the cortex of unfertilized eggs and was
      then transferred to the hyaline layer soon after the fertilization. The hyaline
      layer retained FR-1R immunoreactivity during early embryogenesis. FR-1R appeared
      on the basal side of the ectoderm at the morula stage and was retained
      basolaterally, at least, to the early gastrula stage. In mesenchyme blastulae, FR
      1R was also present on the surface of primary mesenchyme cells (PMC). FR-1R was
      localized on the basal side of the ectoderm in early gastrulae, exclusively at
      the place where PMC formed ventrolateral aggregates, and at the apical tuft
      ectoderm. In vitro, PMC bound to FR-1R and its binding was inhibited in the
      presence of a synthetic RGDS peptide or the pAb. The pAb introduced into the
      blastocoele perturbed PMC migration and gastrulation. FR-1R was weakly recognized
      by antihuman integrin beta5 subunit pAb.

PMID- 11576178
TI  - Developmental study of the different effects on the hybrid sterility of Kit and
      KitW-v alleles paired with Kit from Mus spretus.
AB  - The combination of the KitW or KitW-n mutant alleles and KitS from Mus spretus
      results in male hybrid sterility with small testes. In the present study,
      reproduction of the combination between KitW-v and KitS alleles was examined. The
      KitW-v/KitS male was fertile and the histologic structure was normal; the
      seminiferous tubules showed all of the normal stages of spermatogenesis. The
      postnatal development of the testis at 8, 12, 16 and 20 days was also studied in
      the fertile +Kit/+Kit and KitW-v/KitS males and the sterile KitW/KitS. The
      results showed that at 8 days there was no noticeable difference among the three
      genotype combinations, while from 12 to 20 days spermatogenesis in the KitW/KitS
      male nearly stopped before the meiosis stage. The expression of Kit receptor
      protein from the KitS allele in the sterile testis of the KitW/KitS male was
      confirmed using western blot analysis. The Kit ligand derived from M. spretus
      showed two amino acid changes in the extracellular domain compared with that from
      C57BL and it appears that the ligand-receptor interaction between C57BL and SPR
      may influence the male hybrid sterility of KitW/KitS.

PMID- 11576180
TI  - Scaffolding proteins organize multimolecular protein complexes for sensory signal
      transduction.
AB  - Scaffolding proteins composed of protein-protein interaction domains have emerged
      as organizers of multiprotein complexes in diverse cellular compartments,
      including neuronal synapses, cell-cell junctions of epithelial cells, and the
      stimulus perceiving structures of sensory neurons. This review focuses on the
      INAD-assembled signalling complex of Drosophila photoreceptors, which organizes
      key components of the phototransduction cascade into a multiprotein signal
      transduction unit. The structure, the physiological consequences, and the
      assembly and targeting of the members of the INAD signalling complex will be
      described. In addition, the existence of signalling complexes in vertebrate
      photoreceptors, olfactory neurons and mechanosensitive hair cells will be
      discussed.

PMID- 11576181
TI  - Glutamate receptor stimulation induces a persistent rhythmicity of the GABAergic
      inputs to rat midbrain dopaminergic neurons.
AB  - The substantia nigra pars compacta and the ventral tegmental area are part of a
      complex network in the basal ganglia involved in behaviours as diverse as motor
      planning, generation of pleasure and drug addiction. Here we report that in the
      dopaminergic neurons of the rat ventral midbrain a brief coactivation of group I
      metabotropic and NMDA glutamate receptors may transform a temporally dispersed
      synaptic GABAergic input into a rhythmic pattern (range 4.5-22.5 Hz), probably
      through a mechanism involving electrotonic couplings. The plastic and long
      lasting modification in the temporal code of the inhibitory synaptic activity
      induced by glutamate may be a key element in determining the function of midbrain
      dopaminergic neurons in both normal and pathological behaviour.

PMID- 11576182
TI  - Development of brain-derived neurotrophic factor and neurotrophin-3
      immunoreactivity in the lower auditory brainstem of the postnatal gerbil.
AB  - The localization of brain-derived neurotrophic factor (BDNF) and neurotrophin-3
      (NT-3) in the gerbil auditory brainstem was studied during normal postnatal
      development. The principal objective of this paper was to compare the
      developmental distribution of BDNF and NT-3 proteins to the known developmental
      distribution of their cognate, high-affinity tyrosine kinase receptors. BDNF and
      NT-3 proteins were localized using standard immunohistochemistry. No specific
      immunoreactivity for BDNF or NT-3 was detected on the day of birth (P0) in any
      auditory structure, although fibers comprising the spinal tract of the Vth
      cranial nerve were well labelled with antibodies against BDNF. Diffuse
      immunoreactivity for both BDNF and NT-3 was first detected at P3 in the cochlear
      nucleus and in several second order auditory nuclei in the superior olivary
      complex. This diffuse immunoreactivity became clustered and restricted to
      neuronal cell bodies by P10. Immunoreactivity for both BDNF and NT-3 transiently
      disappeared in the lateral and medial superior olivary nuclei at P10. However,
      neurons in the medial nucleus of the trapezoid body remained immunopositive for
      both BDNF and NT-3. Fibers in the trapezoid body were labelled with BDNF
      immunoreactivity by P12. Between P12 and P15, the distribution of BDNF and NT-3
      immunoreactivity in the cochlear nucleus and superior olivary complex became
      comparable to adult (P140) immunolabel. These results show that the normal
      developmental distribution of the neurotrophins BDNF and NT-3 in the lower
      auditory brainstem occurs during the first two postnatal weeks in parallel with
      the developmental expression of their cognate receptors, trkB and trkC.

PMID- 11576183
TI  - Choroid plexus and ageing in rats: a morphometric and ultrastructural study.
AB  - Choroid plexuses (CP) are intraventricular structures involved in the production
      of cerebrospinal fluid (CSF) and in the synthesis and transport of numerous CSF
      components. Age-related modifications of the CP structure are still ill defined.
      We performed an ultrastructural and morphometric study of ageing CP in nine
      Sprague-Dawley rats 6, 18 and 30 months of age. Epithelial cells of CP villi were
      cubic in shape at 6 months, more dome-like at 18 months, and significantly
      flattened at 30 months of age. Epithelial basement membranes were thin and
      regular at 6 months, significantly thicker at 18 months and thicker and irregular
      at 30 months. Intravillous stroma increased nonhomogeneously with age. The ageing
      of CP in rats is characterized morphologically by epithelial atrophy, irregular
      fibrosis of the stroma and a thickening of epithelial basement membranes. These
      modifications suggest an alteration of secretory and filtrating functions in
      ageing CP.

PMID- 11576184
TI  - Control elements between -9.5 and -3.0 kb in the human tissue-type plasminogen
      activator gene promoter direct spatial and inducible expression to the murine
      brain.
AB  - Tissue-type plasminogen activator (t-PA) participates in the control of synaptic
      plasticity and memory formation in the central nervous system (CNS). Transgenic
      mice harbouring either 9.5, 3.0 or 1.4 kb of the human t-PA promoter fused to the
      LacZ reporter gene were used to assess t-PA promoter-directed expression in vivo.
      The 9.5 kb t-PA promoter directed expression to the brain, most notably to the
      dentate gyrus, superior colliculus, hippocampus, thalamus and piriform cortex.
      Staining was also observed in the retrosplenial and somatosensory cortex. The 3.0
      kb t-PA promoter directed generalized and poorly defined expression to the cortex
      and hippocampus, while the 1.4 kb t-PA promoter directed expression selectively
      to the medial habenula. Intravenous administration of lipopolysaccharide into
      mice harbouring the 9.5 kb t-PA promoter resulted in an increase in reporter gene
      activity in the lateral orbital cortex and thalamus. Results of in vitro
      transfection experiments of NT2 cells with a series of t-PA promoter deletion
      constructs confirmed the presence of regulatory elements throughout the 9.5 kb
      promoter region. Finally, we describe a cis-acting element related to the NFAT
      recognition site that provides a protein-binding site and which may play a role
      in the selective expression of the 1.4 t-PA promoter in the medial habenula.
      These results indicate that elements between -3.0 and -9.5 kb of the t-PA
      promoter confer constitutive and inducible expression to specific regions of the
      CNS.

PMID- 11576185
TI  - Optical imaging of spreading depolarization waves triggered by spinal nerve
      stimulation in the chick embryo: possible mechanisms for large-scale coactivation
      of the central nervous system.
AB  - Using a multiple-site optical recording technique with a voltage-sensitive dye,
      we found that widely spreading depolarization waves were evoked by dorsal root
      stimulation in embryonic chick spinal cords. Spatiotemporal maps of the
      depolarization waves showed that the signals were mainly distributed in the
      ventral half of the slice, with the highest activity in the ventrolateral area.
      The propagation velocity of the waves was estimated to be in the order of mm/s.
      Depolarization waves were evoked in the ventral root-cut preparation, but not in
      the dorsal root-cut preparation, suggesting that the wave was triggered by
      synaptic inputs from the primary afferents, and that activation of the
      motoneurons was not essential for wave generation. In intact spinal cord-brain
      preparations, the depolarization wave propagated rostrally and caudally for a
      distance of several spinal segments in normal Ringer's solution. In a Mg(2+)-free
      solution, the amplitude and extent of the signals were markedly enhanced, and the
      depolarization wave triggered in the cervical spinal cord propagated to the
      brainstem and the cerebellum. The depolarization wave demonstrated here had many
      similarities with the vagus nerve-evoked depolarization wave reported previously.
      The results suggest that functional cell-to-cell communication systems mediated
      by the depolarization wave are widely generated in the embryonic central nervous
      system, and could play a role in large-scale coactivation of the neurons in the
      spinal cord and brain.

PMID- 11576186
TI  - Beta-bungarotoxin is a potent inducer of apoptosis in cultured rat neurons by
      receptor-mediated internalization.
AB  - The neurotoxic phospholipase A(2), beta-bungarotoxin (beta-BuTx), is a component
      of the snake venom from the Taiwanese banded krait Bungarus multicinctus. beta
      BuTx affects presynaptic nerve terminal function of the neuromuscular junction
      and induces widespread neuronal cell death throughout the mammalian and avian
      CNS. To analyse the initial events of beta-BuTx-mediated cell death, the toxin
      was applied to cultured rat hippocampal neurons where it induced neuronal cell
      death in a concentration-dependent manner (EC(50) approximately equal to 5 x 10(
      13) M) within 24 h. Fluorescence labelled beta-BuTx was completely incorporated
      by neurons within < 10 min. Binding and uptake of beta-BuTx, as well as induction
      of cell death, were efficiently antagonized by preincubation with dendrotoxin I,
      a blocker of voltage-gated potassium channels devoid of phospholipase activity.
      Binding of beta-BuTx was selective for neurofilament-positive cells. As evident
      from intense annexin-V and TUNEL stainings, application of beta-BuTx induced
      apoptotic cell death exclusively in neurons, leaving astrocytes unaffected. No
      evidence was obtained for any contribution of either caspases or calpains to beta
      BuTx-induced apoptosis, consistent with the inability of the inhibitors Z-Asp-DCB
      and calpeptin, respectively, to protect neurons from beta-BuTx-induced cell
      death. These observations indicate that induction of cell death by beta-BuTx
      comprises several successive phases: (i) binding to neuronal potassium channels
      is the initial event, followed by (ii) internalization and (iii) induction of
      apoptotic cell death via a caspase-independent pathway.

PMID- 11576187
TI  - Regeneration in avian hair cell epithelia: identification of intracellular
      signals required for S-phase entry.
AB  - Balance epithelia in birds closely resemble their mammalian counterparts, but
      their cells turnover rapidly and they quickly regenerate hair cells, leading to
      functional recovery from damage that would be permanent for a mammal. We isolated
      and cultured sheets of the chicken's utricular epithelium in bromo-deoxyuridine
      and specific inhibitors of different intracellular signalling pathways to
      identify signals that influence turnover and regeneration. Synthesis (S-phase)
      entry was effectively blocked by inhibition of PI3-K, TOR or MAPK, and
      significantly decreased by inhibitors of PKC. Comparisons indicate that activated
      PI3-K and TOR are required for S-phase entry in both avian and mammalian balance
      epithelia, but activation of the MAPK pathway appears to have a more significant
      role in avian utricles than in mammals. The dissimilarities in the requirements
      for these signalling pathways do not appear sufficient to explain the marked
      difference in regenerative capacity between the ears of birds and mammals.

PMID- 11576188
TI  - High expression and anterograde axonal transport of aminoterminal sonic hedgehog
      in the adult hamster brain.
AB  - Sonic hedgehog (SHH) is considered to play an important role in tissue induction
      and patterning during development, particularly in determining neuronal cell fate
      in the ventral neural tube and in the embryonic forebrain. SHH precursor is
      autoproteolytically cleaved to an aminoterminal fragment (SHHN) which retains all
      known SHH biological activities. Here, we demonstrate the expression of a 22-kDa
      SHHN immunoreactive peptide in developing and adult hamster brain regions using a
      rabbit antiserum directed against a mouse SHHN fragment. Interestingly, SHHN was
      developmentally regulated with the highest expression observed in the adult
      brain, was resistant to Triton X-100 solubilization at 4 degrees C and
      partitioned with the raft component ganglioside GM1 during density gradient
      centrifugation. In rat brain, Shh transcripts were identified by double in situ
      hybridization in GABAergic neurons located in various basal forebrain nuclei
      including globus pallidus, ventral pallidum, medial septum-diagonal band complex,
      magnocellular preoptic nucleus and in cerebellar Purkinje cells as well as in
      motoneurons of several cranial nerve nuclei and of the spinal cord. We show that
      radiolabelled SHHN peptides are synthesized in the adult hamster retina and are
      transported axonally along the optic nerve to the superior colliculus in vivo.
      Our data indicate that SHHN is associated with cholesterol rich raft-like
      microdomains and anterogradely transported in the adult brain, and suggest that
      the roles of this extracellular protein are more diverse than originally thought.

PMID- 11576189
TI  - Involvement of intrinsic cholinergic and GABAergic innervation in the effect of
      NMDA on striatal dopamine efflux and metabolism as assessed by microdialysis
      studies in freely moving rats.
AB  - Microdialysis perfusion was used to study the participation of striatal
      cholinergic and gamma-aminobutyric acid-ergic (GABAergic) neurotransmission in
      basal and N-methyl-D-aspartate (NMDA) receptor-modulated dopamine release and
      metabolism in the striatum of the freely moving rat. Reverse dialysis of atropine
      (1-50 microM) induced a concentration-related increase in dopamine efflux and
      decrease in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
      efflux. (+)-Bicuculline (10-100 microM) similarly increased dopamine efflux, but
      was without consistent effect on metabolite efflux. Reverse dialysis of NMDA (1
      mM) evoked an approximately twofold increase in dopamine efflux and decreased
      DOPAC and HVA efflux to 30-40% of basal levels. The effect of NMDA on dopamine
      efflux was completely abolished by coadministration of tetrodotoxin (TTX; 1
      microM) or atropine (10 microM), and markedly potentiated (approximately
      fourfold) by coadministration of (+)-bicuculline (50 microM). The NMDA-induced
      decrease in dopamine metabolite efflux was inhibited by coadministration of TTX
      or (+)-bicuculline, but was unaffected by atropine. Our data suggest that
      dopamine release in the striatum is subject to both cholinergic and GABAergic
      tonic inhibitory mechanisms mediated through muscarinic and GABAA receptors,
      respectively. Furthermore, NMDA-stimulated dopamine release also involves
      obligatory cholinergic facilitation and an inhibitory GABAergic component
      mediated through these respective receptors.

PMID- 11576190
TI  - Dominance of the lurcher mutation in heteromeric kainate and AMPA receptor
      channels.
AB  - Homomeric glutamate receptor (GluR) channels become spontaneously active when the
      last alanine residue within the invariant SYTANLAAF-motif in the third membrane
      segment is substituted by threonine. The same mutation in the orphan GluRdelta2
      channel is responsible for neurodegeneration in "Lurcher" (Lc) mice. Since most
      native GluRs are composed of different subunits, we investigated the effect of an
      Lc-mutated subunit in heteromeric kainate and AMPA receptors expressed in HEK293
      cells. Kainate receptor KA2 subunits, either wild type or carrying the Lc
      mutation (KA2(Lc)), are retained inside the cell but are surface-expressed when
      assembled with GluR6 subunits. Importantly, KA2(Lc) dominates the gating of
      KA2(Lc)/GluR6(WT) channels, as revealed by spontaneous activation and by slowed
      desensitization and deactivation kinetics of ligand-activated whole-cell
      currents. Moreover, the AMPA receptor subunit GluR-B(Lc)(Q) which forms
      spontaneously active homomeric channels with rectifying current-voltage
      relationships, dominates the gating of heteromeric GluR-B(Lc)(Q)/GluR-A(R)
      channels. The spontaneous currents of these heteromeric AMPAR channels show
      linear current-voltage relationships, and the ligand-activated whole-cell
      currents display slower deactivation and desensitization kinetics than the
      respective wild-type channels. For heteromeric Lc-mutated kainate and AMPA
      receptors, the effects on kinetics were reduced relative to the homomeric Lc
      mutated forms. Thus, an Lc-mutated subunit can potentially influence heteromeric
      channel function in vivo, and the severity of the phenotype will critically
      depend on the levels of homomeric GluR(Lc) and heteromeric GluR(Lc)/GluR(WT)
      channels.

PMID- 11576191
TI  - Detection of animals in natural images using far peripheral vision.
AB  - It is generally believed that the acuity of the peripheral visual field is too
      poor to allow accurate object recognition and, that to be identified, most
      objects need to be brought into foveal vision by using saccadic eye movements.
      However, most measures of form vision in the periphery have been done at
      eccentricities below 10 degrees and have used relatively artificial stimuli such
      as letters, digits and compound Gabor patterns. Little is known about how such
      data would apply in the case of more naturalistic stimuli. Here humans were
      required to categorize briefly flashed (28 ms) unmasked photographs of natural
      scenes (39 degrees high, and 26 degrees across) on the basis of whether or not
      they contained an animal. The photographs appeared randomly in nine locations
      across virtually the entire extent of the horizontal visual field. Accuracy was
      93.3% for central vision and decreased almost linearly with increasing
      eccentricity (89.8% at 13 degrees, 76.1% at 44.5 degrees and 71.2% at 57.5
      degrees ). Even at the most extreme eccentricity, where the images were centred
      at 70.5 degrees, subjects scored 60.5% correct. No evidence was found for
      hemispheric specialization. This level of performance was achieved despite the
      fact that the position of the image was unpredictable, ruling out the use of
      precued attention to target locations. The results demonstrate that even high
      level visual tasks involving object vision can be performed using the relatively
      coarse information provided by the peripheral retina.

PMID- 11576192
TI  - Electrical responses reveal the temporal dynamics of brain events during
      involuntary attention switching.
AB  - Surviving in the natural environment requires the rapid switching of attention
      among potentially relevant stimuli. We studied electrophysiologically the
      involuntary switching time in humans performing a task designed to study brain
      mechanisms of involuntary attention and distraction (C. Escera et al., 1998, J.
      Cogn. Neurosci., 10, 590-604). Ten subjects were instructed to discriminate
      visual stimuli preceded by a task-irrelevant sound, this being either a
      repetitive tone (P = 0.8) or a distracting sound, i.e. a slightly higher deviant
      tone (P = 0.1) or an environmental novel sound (P = 0.1). In different
      conditions, the sounds preceded the visual stimuli by 245 or 355 ms. Deviant
      tones and novel sounds prolonged reaction times significantly to subsequent
      visual stimuli by 7.4 (P < 0.02) and 15.2 ms (P < 0.003), respectively. In
      addition to a mismatch negativity (MMN) and a positive-polarity, 320-ms latency,
      P3a event-related potential associated, respectively, with detection of the
      distracting sound and the subsequent orienting of attention to it, a late frontal
      negative deflection was observed in distracting trials. The peak latency of this
      brain response from sound onset was 580 ms in the 245-ms condition and 115 ms
      longer in the 355-ms condition (P < 0.001), peaking consequently at 340 ms from
      visual stimulus onset, irrespective of the onset of the distracting sound. We
      suggest that this late frontal negative response may signal over the scalp the
      process of reallocating attention back to the original task after momentary
      distraction, and therefore that recovering from distraction may take a similar
      shifting time as orienting attention involuntarily towards unexpected novelty.

PMID- 11576193
TI  - The psychoactive ingredient of marijuana induces behavioural sensitization.
AB  - Here we describe, for the first time, the occurrence of behavioural sensitization
      after chronic exposure to Delta9-tetrahydrocannabinol. Rats were treated twice a
      day, for five days, with increasing doses (5, 10, 20, 40, 40 mg/kg i.p.) of
      Delta9-tetrahydrocannabinol or its vehicle and after 20 days of withdrawal,
      animals were challenged with 5 mg/kg (i.p.) of the drug and their behaviour was
      assessed. Contrary to the motor inhibition induced in control rats, challenge
      with Delta9-tetrahydrocannabinol in pre-exposed animals elicited a complex
      behavioural syndrome mainly characterized by oral stereotyped items. Due to the
      relevance of behavioural sensitization in drug-seeking behaviour that persists
      long after discontinuation of drug use, our findings suggest that cannabinoids
      could trigger neurobiological alteration not dissimilar from those observed with
      more harmful abused drugs.

PMID- 11576194
TI  - Temporal characterization of memory retrieval processes: an fMRI study of the
      "tip of the tongue" phenomenon.
AB  - "Tip of the tongue" (TOT) is a natural phenomenon in which people cannot retrieve
      a target word immediately, even though they feel confident that they know the
      target. This provides us an opportunity to understand the human memory system,
      because cognitive components of memory retrieval such as retrieval effort and
      successful retrieval are temporally dissociated from each other during the TOT
      states. The purpose of the present study was to reveal the neural correlates of
      the cognitive components of the retrieval process by separating cognitive phases
      of the TOT phenomenon using event-related functional magnetic resonance imaging
      with multiple regression analysis. We demonstrated that the left dorsolateral
      prefrontal cortex (DLPFC) and anterior cingulate cortex were activated at the
      time of successful retrieval, and the left DLPFC also showed activation when the
      subjects successfully retrieved the target names as compared to when they gave
      up. This result suggests that the left DLPFC is specific to the successful
      retrieval process. During the TOT state, a number of regions were activated, and
      this suggests that widely distributed brain regions are engaged when people make
      a hard effort to retrieve a proper name in the TOT state. Our new approach
      employing temporal resolution of the TOT phenomenon may contribute to the
      understanding of the mechanisms of the human memory system.

PMID- 11576195
TI  - Striatal projections from the cat visual thalamus.
AB  - Anterograde transport methods reveal an extensive thalamostriate projection from
      the extrageniculate visual thalamus. These projections distribute to
      approximately the same regions of the striatum innervated by the corticostriate
      projections from over a dozen higher visual cortical areas [visual-recipient
      sector; Updyke, B.V. (1993) J. Comp. Neurol., 327, 159-193.]. Like their cortical
      counterparts, the thalamostriate projections to the caudate distribute in a
      patchy manner that suggests potential overlap or intermingling spatial
      relationships between the two major afferents. All of the visually related
      thalamic nuclei projecting to the striatum receive ascending signals from the
      superior colliculus, suggesting that the constraints placed upon tectal
      processing by striatonigral control have important consequences for central
      perceptuomotor processing at the striatal and cortical levels.

PMID- 11576196
TI  - Pallidal activity is involved in visuomotor association learning in monkeys.
AB  - In order to examine whether the basal ganglia are involved in arbitrary
      visuomotor association, we recorded neuronal activity in the internal segment of
      the globus pallidus (GPi) of monkeys during a conditional visuomotor learning
      task. Two monkeys were presented a cueing visual stimulus, and following a delay
      period required to push, pull or turn a manipulator according to the cue. GPi
      neurons showed changes in activity during the delay period when the animals
      performed the task on the basis of a familiar stimulus-response association.
      Those changes in delay activity were enhanced as the monkeys were learning a new
      visuomotor association. The enhancement of the changes was selective to a
      following response. These results suggest that the basal ganglia are involved in
      arbitrary visuomotor association, especially during the learning of new
      associations.

PMID- 11576197
TI  - Preference comparison of rizatriptan ODT 10-mg and sumatriptan 50-mg tablet in
      migraine.
AB  - OBJECTIVE: To compare the proportion of patients who prefer rizatriptan orally
      disintegrating tablet (ODT) 10-mg to sumatriptan 50-mg tablet. BACKGROUND:
      Migraineurs express treatment preference based on a variety of attributes
      including the speed of pain relief and medication formulation. Rizatriptan ODT is
      an orally disintegrating formulation of rizatriptan, a selective 5-HT1B/1D
      receptor agonist. This study was conducted to determine patient preference
      between rizatriptan ODT 10-mg and sumatriptan 50-mg tablet for the acute
      treatment of migraine. METHODS: This was a multicenter, randomized, open-label,
      two-period crossover study conducted in the United States with 524 enrolled
      patients. Patients treated a single moderate or severe headache in each treatment
      period. Patients treated one migraine with either rizatriptan ODT 10-mg or
      sumatriptan 50-mg tablet, then treated a second migraine with the alternate
      therapy. Patients completed diary assessments at baseline, and 30, 45, 60, 90,
      and 120 minutes postdose and rated headache severity on a 4-point scale (0 =
      none, 1 = mild, 2 = moderate, and 3 = severe). At the final study visit following
      treatment of their second migraine, patients expressed preference for one of the
      two study medications by completing an interviewer-administered Global Preference
      Question and then responded to a self-administered series of questions to capture
      their most important reason for preferring one study medication over the other.
      Safety measurements were recorded through standard adverse experience reporting.
      RESULTS: Three hundred eighty-six patients treated two migraine attacks. For
      those patients who expressed a preference for either rizatriptan ODT or
      sumatriptan (n = 374), the percentage of patients who preferred rizatriptan ODT
      10-mg (57%, n = 213) was significantly greater than those who preferred
      sumatriptan 50-mg tablet (43%, n = 161) (P<.01). For those patients who treated
      two migraine attacks and had drug severity measures for both attacks (n = 384), a
      significantly greater percentage of patients reported pain relief after taking
      rizatriptan ODT than sumatriptan at the 45- and 60-minute time points (38% versus
      29% and 58% versus 49%, respectively) (P<.01). In addition, a significantly
      greater percentage of patients taking rizatriptan ODT reported a pain-free status
      at the 60- and 120-minute time points (23% versus 17% [P<.05] and 60% versus 52%
      [P<.01], respectively). Both rizatriptan ODT and sumatriptan were well tolerated.
      CONCLUSIONS: A significantly greater proportion of patients preferred rizatriptan
      ODT 10-mg to sumatriptan 50-mg tablet for the acute treatment of migraine.
      Efficacy and safety data are consistent with the preference findings.

PMID- 11576198
TI  - Effect of rizatriptan and other triptans on the nausea symptom of migraine: a
      post hoc analysis.
AB  - OBJECTIVE: To compare the effects of oral rizatriptan, sumatriptan, naratriptan,
      and zolmitriptan on the relief and emergence of nausea during a migraine attack.
      METHODS: Data from five randomized, placebo-controlled, double-blind clinical
      trials in which oral rizatriptan 10 mg was directly compared with oral
      sumatriptan 100 mg (N = 772), 50 mg (N = 1168), 25 mg (N = 1180), naratriptan 2.5
      mg (N = 406), or zolmitriptan 2.5 mg (N = 571) for the acute treatment of a
      migraine attack were retrospectively analyzed. Migraine was diagnosed according
      to International Headache Society criteria. Presence or absence of nausea was
      recorded at baseline and at 0.5, 1, 1.5, and 2 hours after dosing. The end points
      analyzed were relief of nausea in those who had it at baseline and emergence of
      nausea in those who were free of it at baseline. Treatments were compared using
      odds ratios estimated from logistic regression models at 2 hours, and averaged
      odds ratios for the first 2 hours posttreatment. RESULTS: Approximately 60% of
      patients in each treatment group had nausea at baseline. In those patients with
      nausea at baseline, significantly more patients treated with rizatriptan 10 mg
      were free of nausea at 2 hours compared with sumatriptan 100 mg (66% versus 58%,
      P =.043), sumatriptan 50 mg (68% versus 57%, P =.010), sumatriptan 25 mg (68%
      versus 59%, P =.017), and naratriptan 2.5 mg (59% versus 45%, P =.014). Averaging
      over the four posttreatment time points in the first 2 hours, significantly more
      patients treated with rizatriptan 10 mg were free of nausea compared with
      sumatriptan 100 mg (P =.004), sumatriptan 50 mg (P =.001), and naratriptan 2.5 mg
      (P =.015). No significant differences in nausea relief were seen between
      rizatriptan 10 mg and zolmitriptan 2.5 mg, either at 2 hours (65% versus 61%, P
      =.210) or over the first 2 hours (P =.781). Rates of treatment-emergent nausea at
      2 hours ranged from 11% to 18% with placebo, from 5% to 13% with rizatriptan 10
      mg, and from 10% to 20% with other comparator triptans. CONCLUSIONS: Oral
      rizatriptan 10 mg was more effective than oral sumatriptan and naratriptan at
      eliminating nausea within 2 hours in patients who had it at baseline. Rates of
      emergent nausea in patients who were free of it at baseline were low, and no
      consistent differences were observed between active treatments.

PMID- 11576199
TI  - Immunological aspects in migraine: increase of IL-10 plasma levels during attack.
AB  - In the present study, 23 patients with migraine without aura were monitored
      during a migraine attack. Plasma levels of interleukin (IL)-4, IL-5, IL-10, and
      interferon-gamma were measured by enzyme-linked immunosorbent assay techniques.
      Interestingly, we observed low to undetectable IL-5 and IL-4 levels, whereas high
      IL-10 levels were seen in 52.2% of the patients. Interferon-gamma plasma levels
      were undetectable in all patients. After treatment with sumatriptan, 10 patients
      showed a subsequent decrease in IL-10 and an increase in both IL-4 and IL-5
      plasma levels. Although these findings are derived from a limited number of
      patients, the apparent return to the IL-4 and IL-5 cytokine profile observed
      during the interictal period leads us to speculate that a preferential
      enhancement of TH2-type cytokine production may contribute to the pathogenesis of
      migraine.

PMID- 11576200
TI  - Reduction in the intensity of abortive migraine drug use during coumarin therapy.
AB  - OBJECTIVE: To investigate the impact of coumarin therapy on migraine attack
      frequency. BACKGROUND: Sporadic case reports and clinical studies have described
      beneficial effects of coumarin therapy on migraine severity. DESIGN AND METHODS:
      A retrospective follow-up study based on a prescription database covering a
      population of 450 000 was conducted. All patients using an abortive migraine drug
      (ergotamine or sumatriptan) and subsequently treated with either coumarin (index
      group) or low-dose acetylsalicylic acid (control group) were analyzed. The impact
      of coumarin and low-dose acetylsalicylic acid on the frequency of migraine
      attacks was assessed by measuring the intensity of ergotamine and sumatriptan
      use, in defined daily doses per month per patient, before and during coumarin or
      acetylsalicylic acid treatment. In addition, a "therapeutic intensity reduction"
      was determined for each patient. RESULTS: The study population consisted of 92
      patients; 35% had been prescribed coumarin and 65% had been prescribed low-dose
      acetylsalicylic acid after the initiation of ergotamine or sumatriptan. Two
      thirds of the study population was treated with ergotamine. Overall, ergotamine
      and sumatriptan use for the coumarin cohort decreased from 6.4 defined daily
      doses per month prior to coumarin treatment to 3.0 defined daily doses during
      coumarin treatment, compared with a reduction from 5.2 defined daily doses per
      month to 4.4 defined daily doses per month for the low-dose acetylsalicylic acid
      cohort (P>.05). The therapeutic intensity of ergotamine and sumatriptan use was
      significantly decreased by 40% for the coumarin cohort, compared with 4.7% for
      the low-dose acetylsalicylic acid cohort (P=.004). CONCLUSIONS: We observed that
      coumarin treatment was clearly associated with a reduction in the therapeutic
      intensity of abortive migraine drug use in comparison with low-dose aspirin
      treatment. This suggests that, overall, the coumarin cohort had experienced a
      substantial reduction in the frequency of migraine attacks during anticoagulation
      treatment. Our findings, as well as those of others, justify a controlled
      clinical trial to further establish the effects of coumarin therapy on migraine
      severity and its possible role in the prophylactic management of patients
      suffering from migraine.

PMID- 11576201
TI  - Valproic acid is effective in migraine prophylaxis at low serum levels: a
      prospective open-label study.
AB  - OBJECTIVE: We evaluated the efficacy of prophylactic valproic acid treatment (6
      months) on the frequency of migraine attacks and the number of migraine headache
      days with respect to serum levels. BACKGROUND: Valproic acid, a GABAergic drug,
      has been shown to be effective for migraine prophylaxis. Results from several
      dose- and serum level-adjusted studies have recommended valproic acid doses
      within a range of 500 to 1500 mg per day for migraine prophylaxis. DESIGN AND
      METHODS: In this prospective open-label study, 52 patients received valproic acid
      doses of 300 to 1200 mg per day; 45 patients were treated per protocol. Valproic
      acid serum levels increased linearly in relation to the valproic acid dose and
      were between 21 and 107 microg/mL at the end of the treatment period. Patients
      were divided into two groups: those with valproic acid serum levels less than 50
      microg/mL (group 1) and those with serum levels greater than 50 microg/mL (group
      2). RESULTS: The frequency of migraine attacks was significantly reduced in group
      1 from 3.5 +/- 0.9 to 2.0 +/- 0.9 attacks per month. Migraine headache days also
      decreased (6.4 +/- 3.5 to 4.6 +/- 2.9 days per month). In the high serum level
      group, a reduction of migraine attacks from 3.5 +/- 0.9 to 2.8 +/- 1.0 attacks
      per month and only a slight decrease in headache days (6.4 +/- 3.5 to 6.1 +/- 2.4
      days per month) was observed. The outcome of group 1 (low serum level) was
      significantly better than that of group 2 with respect to both parameters
      (P<.05). Side effects were generally mild and temporary. CONCLUSIONS: Due to the
      lack of additional benefit from higher valproic acid doses (more than 600 mg per
      day), we recommend daily valproic acid doses of 500 to 600 mg with a target serum
      level less than 50 microg/mL for the prophylactic treatment of migraine.

PMID- 11576202
TI  - Is blood homocysteine elevated in migraine?
AB  - OBJECTIVE: To determine total serum homocysteine levels in a large group of
      patients with migraine with and without aura. BACKGROUND: Hypercoagulable state
      is a known risk factor for stroke in the young. The existence of a
      hypercoagulable state has been postulated in migraine and homocysteinemia with
      young-onset stroke. To the best of our knowledge, blood homocysteine has not been
      studied in a significant number of patients with various forms of migraine.
      METHODS: Total serum homocysteine was measured with high-performance liquid
      chromatography in 78 patients with migraine and in 126 age- and sex-matched
      healthy volunteers. RESULTS: Seventy-eight patients aged 18 to 65 years were
      studied: 22 with migraine with aura and 56 with migraine without aura. Only 1 man
      had significantly elevated blood homocysteine (38.6 micromol/L), while another
      had a borderline elevation (15.8 micromol/L) (reference value for both sexes in
      our laboratory is 4 to 14 micromol/L). Both patients suffered from migraine
      without aura. CONCLUSIONS: Blood homocysteine is not elevated in migraine.

PMID- 11576203
TI  - Effects of medication use on health state in postictal migraineurs.
AB  - We investigated whether headache-free patients with migraine report a lower
      health state compared with healthy controls, and whether health state is
      differently affected during the postattack period after using sumatriptan versus
      habitual nonvasoactive medication. Mood, health state, and personality
      questionnaires were administered once during an interictal period and twice
      within 30 hours after different migraine attacks treated with sumatriptan or
      habitual nonvasoactive medication. Twenty migraineurs without aura, 10
      migraineurs with aura, and 30 matched and headache-free controls participated in
      this study. During an interictal period, patients with migraine reported more
      problems regarding social activities and pain compared with healthy controls.
      During the postictal period, mood (fatigue and emotional state) was negatively
      affected by an attack that was treated with habitual medication, whereas health
      state (physical pain, social activities, current pain) was similar to the
      migraine-free period. Sumatriptan treatment had beneficial effects on aspects of
      health state and mood during the postictal period.

PMID- 11576204
TI  - Spectral analysis of visual potentials evoked by pattern-reversal checkerboard in
      juvenile patients with headache.
AB  - Changes in visual evoked potentials, mainly affecting the amplitude of the major
      positive wave, are referred to by many authors and are related to the
      pathophysiological basis of primary headache. We performed both transient pattern
      reversal visual evoked potentials and spectral analysis by means of fast Fourier
      transform of 8-Hz steady-state pattern-reversal visual evoked potentials in 34
      children affected with migraine (14 with aura, 20 without aura), and compared
      them with 14 patients with tension-type headache and 10 healthy subjects. The
      amplitude of the response to the transient stimulation (P100) was higher and the
      latency shorter in the patients with headache compared with the controls, but the
      difference was not statistically significant. The absolute power of the first
      harmonic (1F) obtained by the spectral analysis of the steady-state stimulation
      was increased in all the patients with headache compared with the controls, and
      the increase was significant in patients with migraine. These data seem to
      confirm the hypothesis of abnormal processing of visual input in migraineurs and
      could be interpreted as neurophysiological support for the theory that different
      headache types are related conditions. Furthermore, the spectral analysis of
      steady-state pattern-reversal visual evoked potentials could be proposed as a
      test to diagnose migraine.

PMID- 11576205
TI  - Prevalence and clinical characteristics of headache in medical students in oman.
AB  - OBJECTIVES: To perform a descriptive epidemiological study of headache in medical
      students at Sultan Qaboos University, analyzing prevalence, symptom profile, and
      pattern of health care utilization. BACKGROUND: Headache is one of the most
      common complaints in medical practice. To our knowledge, headache has not been
      the subject of investigation in medical students in the Arabian Gulf. METHODS:
      Lifetime and last-year prevalence of headache was based on a detailed structured
      headache assessment questionnaire. Besides demographic data, headache
      characteristics and pattern of health care utilization were evaluated. In
      addition, questions were included referring to the use of traditional remedies.
      Interviewers included three previously trained final-year medical students. The
      evaluation was done per cohort, and the students were guided through the
      assessment questionnaire by the interviewers. Migraine and tension-type headache
      were diagnosed according to the criteria of the International Headache Society.
      RESULTS: Four hundred three students (95.3%) completed the questionnaire: 151 men
      (37.5%) and 252 women (62.5%). The lifetime and last-year prevalence of headache
      was 98.3% and 96.8%, respectively. A positive family history of headache was
      found in 57.6% of students. The prevalence rate of migraine and tension-type
      headache was found to be the same (12.2%), with a difference in distribution
      across sexes: 6.6% of the men and 15.5% of the women had migraine, while 13.9% of
      the men and 11.1% of the women suffered from tension-type headache. Only 23.3% of
      students sought medical assistance during headache episodes, and 80.3% took
      medication: 24.6% took prescribed medication, 72.9% took nonprescription
      medication, and only 2.5% took traditional remedies. Acetaminophen (83.1%)
      followed by mefenamic acid (24.6%) were the most commonly used drugs.
      CONCLUSIONS: The results of this prospective epidemiological study show that
      headache is highly prevalent among medical students at this university. The high
      prevalence rate of migraine sufferers in this student population might be due to
      the high female-to-male ratio (1.7:1). It is likely that analgesic use/overuse
      also coexists with headache in medical students at Sultan Qaboos University,
      since a large majority of them rely on nonprescription medications.

PMID- 11576206
TI  - Prevalence of migraine in Croatia: a population-based survey.
AB  - OBJECTIVES: The aim of the present study was to estimate the prevalence of
      migraine among Croatian adults. This is the first epidemiological study of
      migraine in Croatia in which the operational diagnostic criteria of the
      International Headache Society have been applied. METHODS: The study population
      consisted of all residents (aged 15 to 65 years) of Bakar, County of The Coast
      and Gorski Kotar, Croatia. A population-based survey was undertaken using a "face
      to-face, door-to-door" interview METHOD: The participation rate was 73.3%. All
      participants were screened for headache history according to the International
      Headache Society criteria. Headache screen positive responders (65.7%) were
      interviewed by trained medical students with a structured detailed interview
      focused on migraine. RESULTS: A total of 720 lifetime migraineurs were
      identified. The lifetime prevalence of migraine was 22.9% (95% confidence
      interval, 20.9 to 25.1) in women, 14.8% (95% confidence interval, 13.1 to 16.8)
      in men, and 19% (95% confidence interval, 17.6 to 20.5) in both sexes. The
      highest lifetime prevalence of migraine was in women in the age group 40 to 49
      years (38.1%). Among 636 active migraineurs, 399 (62.7%) were women and 237
      (37.3%) were men; 55.8% had migraine without aura, 35.2% migraine with aura, and
      6.9% migraine both with and without aura. The 1-year prevalence of migraine,
      migraine without aura, migraine with aura, and migraine both with and without
      aura in women was 18%, 11.3%, 8.6%, and 2.2%, respectively. In men, the 1-year
      prevalence of migraine, migraine without aura, migraine with aura, and migraine
      both with and without aura was 12.3%, 7.3%, 3%, and 0.7%, respectively.
      CONCLUSIONS: The prevalence of migraine in this Croatian population showed rates
      quite similar to those reported in neighboring countries, such as Italy and
      France. Further studies are needed to estimate the prevalence rates of migraine
      in the total Croatian population.

PMID- 11576207
TI  - Olanzapine as an abortive agent for cluster headache.
AB  - OBJECTIVE: To evaluate olanzapine as a cluster headache abortive agent in an open
      label trial. BACKGROUND: Cluster headache is the most painful headache syndrome
      known. There are very few recognized abortive therapies for cluster headache and
      fewer for patients who have contraindications to vasoconstrictive drugs. METHODS:
      Olanzapine was given as an abortive agent to five patients with cluster headache
      in an open-label trial. The initial olanzapine dose was 5 mg, and the dose was
      increased to 10 mg if there was no pain relief. The dosage was decreased to 2.5
      mg if the 5-mg dose was effective but caused adverse effects. To be included in
      the study, each patient had to treat at least two attacks with either an
      effective dose or the highest tolerated dose. RESULTS: Five patients completed
      the investigation (four men, one woman; four with chronic cluster, one with
      episodic cluster). Olanzapine reduced cluster pain by at least 80% in four of
      five patients, and two patients became headache-free after taking the drug.
      Olanzapine typically alleviated pain within 20 minutes after oral dosing and
      treatment response was consistent across multiple treated attacks. The only
      adverse event was sleepiness. CONCLUSIONS: Olanzapine appears to be a good
      abortive agent for cluster headache. It alleviates pain quickly and has a
      consistent response across multiple treated attacks. It appears to work in both
      episodic and chronic cluster headache.

PMID- 11576208
TI  - Prolonged recovery from rebound headaches.
AB  - OBJECTIVE: To document that some patients with rebound headache require prolonged
      complete avoidance of the pain relief medications which might cause the daily or
      almost daily headaches in order to achieve a goal of 6 consecutive headache-free
      days. BACKGROUND: Most articles on rebound headache imply that the patient
      improves after stopping the offending agents, but they fail to state the pattern
      of recovery, the time required for recovery, or the specific end point achieved.
      DESIGN: Selected from the histories of approximately 1000 patients with suspected
      rebound headache who have been seen in a university headache referral clinic are
      the records of four patients who kept careful headache diaries, followed the
      treatment protocol (with minimal noncompliance by two patients), and required
      more than 6 months to achieve our goal of 6 consecutive headache-free days.
      CONCLUSIONS: Hopefully, other physicians treating patients with suspected rebound
      headache will benefit from this report and will be able to better manage their
      patients.

PMID- 11576209
TI  - Persistent migrainous visual phenomena might be responsive to lamotrigine.
AB  - Two patients with migraine reported having experienced persistent auralike visual
      phenomena for months to years. All laboratory investigations were normal except
      for occipital hypoperfusion on the brain single photon emission computed
      tomography. After lamotrigine treatment for 2 weeks, they both had a resolution
      of the visual symptoms. Persistent migrainous visual phenomena are potentially
      benign and probably a status of spontaneous aura.

PMID- 11576210
TI  - Statuslike SUNCT in two young women.
AB  - OBJECTIVE: To describe the statuslike pattern of SUNCT (short-lasting unilateral
      neuralgiform pain with conjunctival injection and tearing) in two young women.
      BACKGROUND: SUNCT syndrome is a rare condition characterized by a short-lasting
      periocular pain associated with marked autonomic symptoms. Twenty-five cases have
      been reported in the literature with a high preponderance of males and a mean age
      of 51 years. The frequency of episodes shows a wide variability, not just among
      individuals but also in the same patient, and a statuslike pattern of almost
      continuous attacks has been described. METHODS: We report the cases of two young
      women (aged 26 and 23 years) with typical SUNCT features who suffered bouts of up
      to 60 paroxysms of pain per hour. Paraclinical investigations showed no
      abnormalities. CONCLUSIONS: Although unusual, paroxysms in SUNCT may overlap into
      a clinical status. A strong relationship with hormonal changes was noted in one
      patient. In both cases, the pain was refractory to treatment with indomethacin,
      carbamazepine, and hypnotics, and only intravenous methylprednisolone with oral
      carbamazepine may have been partially effective in one case.

PMID- 11576211
TI  - Etiology and treatment of new daily persistent headache.

PMID- 11576212
TI  - Topiramate for headaches.

PMID- 11576213
TI  - Immunotherapy of melanoma.

PMID- 11576214
TI  - Regulated T-cell development: a victim of multiple conspiracies.

PMID- 11576215
TI  - Assessing a role for enhancer-blocking activity in gene regulation within the
      murine T-cell receptor alpha/delta locus.
AB  - Although situated close together within the T-cell receptor (TCR) alpha/delta
      locus, TCR delta and TCR alpha gene segments are controlled by two developmental
      stage-specific enhancers and are activated according to distinct developmental
      programmes. We previously used a stable transfection colony assay to identify an
      enhancer-blocking element, blocking element alpha/delta-1 (BEAD-1), between the
      TCR delta and alpha gene segments of the human TCR alpha/delta locus. We
      hypothesized that enhancer-blocking by BEAD-1 might be required to prevent the
      TCR delta enhancer from activating TCR alpha gene segment transcription and
      rearrangement at the double negative stage of thymocyte development. Here, we
      used a transfection approach to define partial enhancer-blocking activity in an
      analogous position of the murine TCR alpha/delta locus. To test the functional
      significance of this activity in vivo, we used gene targeting to delete the
      region from the endogenous locus. We found no perturbation of TCR delta and TCR
      alpha gene expression and rearrangement on targeted alleles, indicating that
      enhancer-blocking activity in this region is not required to maintain the
      developmentally distinct activation profiles of the two genes. We suggest that
      appropriate regulation may be achieved as a result of intrinsic biases in
      enhancer-promoter interactions or a developmental stage specificity to promoter
      function that is distinct from any additional specificity imposed by the
      enhancers themselves.

PMID- 11576216
TI  - In vitro stimulation with a non-peptidic alkylphosphate expands cells expressing
      Vgamma2-Jgamma1.2/Vdelta2 T-cell receptors.
AB  - The majority of peripheral blood gammadelta T cells in healthy adult humans
      express the Vgamma2/Vdelta2 T-cell receptor (TCR) and generate TCR-mediated,
      major histocompatibility complex (MHC)-unrestricted proliferative responses to
      low molecular weight alkylphosphates. Vgamma2/Vdelta2 populations after antigen
      proliferation maintained diversity in the CDR3s of Vgamma2 mRNA, indicating that
      the response was polyclonal or oligoclonal, and were enriched for Vgamma2 TCR
      chains containing the Jgamma1.2 segment. Alkylphosphate stimulation further
      skewed an already biased peripheral blood gammadelta T-cell population and
      increased the abundance of Vgamma2-Jgamma1.2/Vdelta2 T cell receptors, suggesting
      similarities between the alkylphosphate response and peripheral selection
      mechanisms shaping this repertoire in human beings.

PMID- 11576217
TI  - Inhibition of the function of the FcgammaRIIB by a monoclonal antibody to thymic
      shared antigen-1, a Ly-6 family antigen.
AB  - Thymic shared antigen-1 (TSA-1) is a member of the Ly-6 family of glycosyl
      phosphatidylinositol (GPI)-linked proteins. While it has been proposed that TSA-1
      may play a role in thymic development, a physiological ligand for this antigen
      has not been identified. Here we report that a monoclonal antibody (mAb) to TSA
      1, generated by immunizing a hamster with CD40 ligand (CD40L)-activated B cells,
      interferes with the function of FcgammaRIIB on splenic B cells and the B-cell
      lymphoma cell line, M12, by binding to TSA on the same cells. The interaction of
      anti-TSA with FcgammaRIIB resulted in an inhibition of the ability of the
      FcgammaRIIB to cross-link and/or aggregate soluble anti-CD3 or soluble anti-Cbeta
      T-cell receptor (TCR), leading to an inhibition of induction of expression of
      CD25 and CD69, interleukin (IL)-2 production and proliferation of naive T cells.
      Cross-blocking studies with mAbs strongly suggested that a physical association
      exists between TSA-1 and the FcgammaRIIB on the surface of activated B cells and
      favour the view that a functional intermolecular association exists between these
      two distinct membrane antigens.

PMID- 11576218
TI  - Cleavage of E2F-1-regulating proteins and activation of E2F-1 during CD95-induced
      death of thymocytes.
AB  - The CD95 death receptor activates caspases that cleave a variety of intracellular
      substrates, including cell cycle control proteins. However, the significance of
      this cleavage for the induction of apoptosis is unclear. In this study, CD95
      induced cleavage of the G1/S checkpoint regulator proteins, retinoblastoma
      protein (pRb) and murine-double-minute-2 (mdm-2), was associated with an
      increased protein concentration of a key transcription factor, E2F-1, which is
      regulated by both of them. Furthermore, DNA-binding activity to E2F sites is
      increased. In thymocytes, CD95-induced apoptosis was associated with increased
      E2F-1 DNA-binding activity, while thymocytes that lacked E2F-1 were less
      susceptible to CD95-induced apoptosis. We conclude that the G1/S checkpoint is an
      important target of CD95 signalling. CD95-activated caspases cleave regulator
      proteins to increase E2F-1 activity, and inappropriate activation of E2F-1 is
      part of the mechanism of CD95-induced apoptosis.

PMID- 11576220
TI  - Schiff base-mediated co-stimulation primes the T-cell-receptor-dependent calcium
      signalling pathway in CD4 T cells.
AB  - In addition to macromolecular interactions that provide co-stimulation during
      antigen-presenting cell (APC) and CD4+ T-cell conjugation, covalent chemical
      events between specialized ligands have been implicated in T-cell co-stimulation.
      These take the form of transient Schiff base formation between carbonyls and
      amines expressed on APC and T-cell surfaces. Small Schiff base-forming molecules,
      such as tucaresol, can substitute for the physiological donor of carbonyl groups
      and provide co-stimulation to T cells, thereby functioning as orally active
      immunopotentiatory drugs. The Schiff base co-stimulatory pathway in T cells has
      been partially characterized in terms of changes in Na+ and K+ transport, and
      activation of the mitogen activated protein kinase (MAPK) ERK2. In the present
      study, the effects of Schiff base co-stimulation by tucaresol on the T-cell
      receptor (TCR)-dependent pathway leading to Ca2+ release were investigated.
      Schiff base co-stimulation by tucaresol was found to prime for enhanced TCR
      dependent phospholipase C-gamma phosphorylation, inositol 1,4,5-triphosphate
      production, and Ca2+ mobilization that correlated with functional enhancement of
      interleukin-2 production in primary T cells. The effects on Ca2+ occurred
      comparably in Jurkat and primary CD4+ T cells responding to anti-CD3 monoclonal
      antibody. Enhancement of the Ca2+ response required a 10-min priming period and
      was prevented by prior covalent ligation of cell-surface free amino groups by
      sulpho-N-hydroxy succinimido-biotin; clofilium-mediated inhibition of tucaresol
      induced changes in intracellular K+; and selective inhibition of the MAPK
      pathway. The data are consistent with a priming mechanism in which late co
      stimulation-triggered events exert a positive influence on early TCR-triggered
      events. In additional studies of murine T cells expressing trans-gene TCRs,
      tucaresol was likewise shown to prime for enhanced Ca2+ mobilization in response
      to physiological TCR-engagement by MHC-peptide complexes.

PMID- 11576219
TI  - Enhancement of stromal cell-derived factor-1alpha-induced chemotaxis for CD4/8
      double-positive thymocytes by fibronectin and laminin in mice.
AB  - Stromal cell-derived factor-1alpha (SDF-1alpha) is a chemokine abundantly
      expressed in the thymus. However, a potential role of SDF-1alpha in the thymus
      has been under consideration, since no appreciable difference was detected in the
      migratory responsiveness to the SDF-1alpha between cortical and medullary
      thymocytes. In the present study, we examined the effects of extracellular matrix
      (ECM) on the responsiveness of murine thymocytes to several chemokines including
      SDF-1alpha. In the absence of ECM, chemotactic activity of SDF-1alpha for
      cortical (CD4/8 double-positive) thymocytes was almost same as that for medullary
      (CD4 or CD8 single-positive) thymocytes. In contrast, the chemotactic activity of
      SDF-1alpha for cortical thymocytes was considerably (more than 10-fold) enhanced
      by laminin or fibronectin as compared with that for medullary thymocytes.
      Chemotactic activities of macrophage-derived chemokine and macrophage
      inflammatory protein-3beta for both cortical and medullary thymocytes were only
      slightly enhanced by fibronectin or laminin. Thus, fibronectin and laminin appear
      to enhance the chemotactic activity of SDF-1alpha for cortical thymocytes
      selectively. Addition of a monoclonal antibody against CD29 showed no inhibitory
      effect on the enhanced chemotactic activity of SDF-1alpha, suggesting that the
      other unknown receptor(s) is involved in this enhancement. Our present data
      demonstrate that SDF-1alpha in the presence of fibronectin or laminin is involved
      in the distribution of developing thymocytes.

PMID- 11576221
TI  - Identification of canine helper T-cell epitopes from the fusion protein of canine
      distemper virus.
AB  - The fusion protein of canine distemper virus (CDV-F), a 662 amino-acid envelope
      protein, was used as the target molecule for identification of canine T helper
      (Th) epitopes. A library of 94 peptides, each 17 residues in length overlapping
      by 10 residues and covering the entire sequence of CDV-F, was screened using a
      lymphocyte proliferation assay with peripheral blood mononuclear cells (PBMC)
      obtained from dogs inoculated with canine distemper virus (CDV) vaccine.
      Initially we observed low and inconsistent proliferation of PBMC in response to
      these peptides, even when using cells obtained from dogs that had received
      multiple doses of CDV. Subsequently, the use of expanded cell populations derived
      by in vitro stimulation of canine PBMC with pools of peptides allowed the
      identification of a number of putative canine Th-epitopes within the protein
      sequence of CDV-F. There were two major clusters of Th-epitopes identified close
      to the cleavage site of the F0 fusion protein, while some others were scattered
      in both the F1 and F2 fragments of the protein. Some of these peptides, in
      particular peptide 35 (p35), were stimulatory in dogs of different breeds and
      ages. The identification of such promiscuous canine Th-epitopes encouraged us to
      assemble p35 in tandem with luteinising hormone releasing hormone (LHRH) a 10
      amino-acid residue synthetic peptide representing a B-cell epitope which alone
      induces no antibody in dogs. The totally synthetic immunogen was able to induce
      the production of very high titres of antibodies against LHRH in all dogs tested.
      These results indicate that p35 could be an ideal candidate for use as a Th
      epitope for use in outbred dogs.

PMID- 11576222
TI  - Evidence of the extrathymic development of tyrosinase-related protein-2
      recognizing CD8+ T cells with low avidity.
AB  - The majority of the human tumour-associated antigens characterized to date are
      derived from non-mutated self-proteins. However, nothing is known about the
      development of autoreactive and tumour-associated antigen-recognizing T cells.
      Tyrosinase-related protein (TRP)-2 is a non-mutated melanocyte differentiation
      antigen and TRP-2-recognizing CD8+ T cells are known to show responses to
      melanoma both in humans and mice. In addition, TRP-2-reactive T cells with low
      avidity have been suggested to be readily induced from the spleen cells of naive
      mice. On the other hand, recent reports suggest that self antigen-reactive CD8+ T
      cells can be positively selected in the periphery. In this study, we tested the
      possibility that TRP-2-reactive CD8+ T cells in naive mice could develop via the
      extrathymic pathway. As a consequence, TRP-2-reactive CD8+ T cell precursors in
      naive C57BL/6 mice were suggested to express both interleukin-2 (IL-2) receptor
      beta chain (IL-2Rbeta) and CD44 molecules, in a manner similar to that of
      extrathymically developed T cells. Furthermore, IL-2Rbeta+ CD44+ CD8+ T cells
      were detected in the adult thymectomized and bone marrow-reconstituted mice, and
      functional TRP-2-reactive T cells were generated from their spleen cells.
      Overall, these results suggest that low avidity CD8+ T cells recognizing TRP-2
      can be developed extrathymically.

PMID- 11576223
TI  - Enumeration of hepatitis B surface antigen-specific B lymphocytes in responder
      and non-responder normal individuals vaccinated with recombinant hepatitis B
      surface antigen.
AB  - Determination of the frequency of specific B lymphocytes has important
      implications for investigation of the immune response to different antigens and
      pathogens. Unresponsiveness to some viruses and antigens, such as hepatitis B
      virus (HBV) and its surface antigen (HBsAg), has been attributed to lack or
      insufficient production of the specific B-cell repertoire. In this study,
      peripheral blood B lymphocytes of 45 adult normal individuals vaccinated with
      recombinant hepatitis B vaccine were transformed with Epstein-Barr virus (EBV)
      and cultured at different dilutions on human fetal fibroblasts as a feeder layer.
      The vaccinees were classified into good, poor and non-responder groups. Following
      2 to 3 weeks of incubation, culture supernatants were collected from wells
      containing transformed and proliferating B lymphocytes. The supernatants were
      subsequently screened for the presence of total immunoglobulin and antibody to
      HBsAg (anti-HBs) by enzyme-linked immunosorbent assay (ELISA). Accordingly,
      positive and negative wells were enumerated in each plate and the frequency of B
      lymphocytes producing anti-HBs antibody was estimated based on the Poisson
      statistical analysis. The total number of CD19+ B lymphocytes were counted in the
      peripheral blood of all subjects by flow cytometry. Our results demonstrated a
      similar precursor frequency of specific B lymphocytes in all subject groups
      before vaccine administration (< 2 x 10(-5)). Following vaccination, however, a
      significant increase in the number of specific B lymphocytes was observed in good
      responder (1.5 x 10(-4)) and to a lesser extent poor-responder (3.5 x 10(-5))
      individuals, but not in non-responders. These findings suggest a defect in either
      the primary B-cell repertoire or helper T-cell function in non-responder
      individuals.

PMID- 11576224
TI  - Medroxyprogesterone acetate enhances in vivo and in vitro antibody production.
AB  - In the present study we examine the effects of medroxyprogesterone acetate (MPA)
      on the specific antibody secretion to T-dependent antigens. Our results show that
      the in vivo administration of MPA to mice, 7 or 90 days before immunization with
      sheep red blood cells (SRBC), significantly enhanced both, primary and secondary
      antibody responses, without affecting delayed-type hypersensitivity (DTH). These
      effects could be counteracted by the anti-progestin onapristone or ZK 98299 (ZK)
      suggesting that MPA interacted with progesterone (PRG) receptors to increase B
      cell response. To better understand the mechanisms involved in MPA activity we
      carried out cultures of splenocytes, bone marrow cells or lymph node cells from
      immunized mice in the presence of MPA, and evaluated the amount of antibody
      release to supernatants. We found that low doses of MPA (10(-9) M and 10(-10) M)
      significantly enhanced the in vitro production of specific immunoglobulin G (IgG)
      antibodies, an effect that appears to involve the interaction of the progestin
      with PRG receptors, as judged by the inhibition of MPA effects with ZK (10(-8) M)
      or RU486 (10(-9) M). These receptors were detected by flow cytometry analysis in
      a proportion of T lymphocytes. Because MPA did not increase the number of
      immunoglobulin-secreting cells, our findings suggest that MPA enhanced the
      capacity of individual cells to produce specific immunoglobulin.

PMID- 11576225
TI  - Fcgamma receptor polymorphisms in populations in Ethiopia and Norway.
AB  - Seventy-seven healthy Ethiopians were genotyped for polymorphisms in the
      immunoglobulin G Fc receptors (FcgammaR) FcgammaRIIa, FcgammaRIIIa and
      FcgammaRIIIb, including the SH allele. The genotype and allele frequencies were
      compared with those of 96 healthy Norwegians. Ethiopians had higher frequencies
      of the SH-FcgammaRIIIb (P = 0.001), FcgammaRIIIa-158 V (P = 0.026) and
      FcgammaRIIIb-Na2 (P = 0.046) alleles. The genotype distributions of FcgammaRIIa,
      FcgammaRIIIa and FcgammaRIIIb, however, did not differ significantly from those
      of the Norwegians. The data were also compared with those reported from studies
      on other ethnic groups. The variation of different polymorphisms both within and
      between ethnic groups may influence differences in the incidence rates of
      infectious and autoimmune diseases.

PMID- 11576226
TI  - Neutralization of interferon-gamma in neonatal SOCS1-/- mice prevents fatty
      degeneration of the liver but not subsequent fatal inflammatory disease.
AB  - Mice lacking the suppressor of cytokine signalling-1 (SOCS1) die within weeks of
      birth with extensive fatty degeneration of the liver, consistent with acute
      hepatic toxicity to interferon-gamma (IFN-gamma), and inflammation of multiple
      organs. We show here that treatment for 1 week from birth with neutralizing
      antibody to IFN-gamma rescues SOCS1-/- mice from lethal liver disease but the
      mice subsequently succumb to chronic inflammatory lesions characterized by T
      lymphocyte infiltration of skeletal muscle, pancreas, lung, liver and skin.
      Elevated blood levels of eosinophils, neutrophils and platelets were also
      observed and the thymic lymphocyte population was depleted of CD4+ CD8+ T cells
      and showed a reduced CD4 : CD8 ratio. All T-cell populations in thymus, spleen
      and lymph node exhibited an increased proportion of cells bearing the activation
      marker CD44. These data suggest an important role for SOCS1 in T-lymphocyte
      regulation.

PMID- 11576227
TI  - Changes in gene expression in macrophages infected with Mycobacterium
      tuberculosis: a combined transcriptomic and proteomic approach.
AB  - We investigated the changes which occur in gene expression in the human
      macrophage cell line, THP1, at 1, 6 and 12 hr following infection with
      Mycobacterium tuberculosis. The analysis was carried out at the transcriptome
      level, using microarrays consisting of 375 human genes generally thought to be
      involved in immunoregulation, and at the proteomic level, using two-dimensional
      gel electrophoresis and mass spectrometry. The analysis of the transcriptome
      using microarrays revealed that many genes were up-regulated at 6 and 12 hr. Most
      of these genes encoded proteins involved in cell migration and homing, including
      the chemokines interleukin (IL)-8, osteopontin, monocyte chemotactic protein-1
      (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha), regulated on
      activation, normal, T-cell expressed and secreted (RANTES), MIP-1beta, MIP
      3alpha, myeloid progenitor inhibitory factor-1 (MPIF-1), pulmonary and activation
      regulated chemokine (PARC), growth regulated gene-beta (GRO-beta), GRO-gamma, MCP
      2, I-309, and the T helper 2 (Th2) and eosinophil-attracting chemokine, eotaxin.
      Other genes involved in cell migration which were up-regulated included the
      matrix metalloproteinase MMP-9, vascular endothelial growth factor (VEGF) and its
      receptor Flk-1, the chemokine receptor CCR3, and the cell adhesion molecules
      vesicular cell adhesion molecule-1 (VCAM-1) and integrin a3. In addition to the
      chemokine response, genes encoding the proinflammatory cytokines IL-1beta
      (showing a 433-fold induction), IL-2 and tumour necrosis factor-alpha (TNF
      alpha), were also found to be induced at 6 and/or 12 hr. It was more difficult to
      detect changes using the proteomic approach. Nevertheless, IL-1beta was again
      shown to be strongly up-regulated. The enzyme manganese superoxide dismutase was
      also found to be strongly up-regulated; this enzyme was found to be macrophage-,
      rather than M. tuberculosis, derived. The heat-shock protein hsp27 was found to
      be down-regulated following infection. We also identified a mycobacterial
      protein, the product of the atpD gene (thought to be involved in the regulation
      of cytoplasmic pH) in the infected macrophage extracts.

PMID- 11576229
TI  - Tumor suppressor genes: new pathways in gynecological cancer.
AB  - The Retinoblastoma (Rb-1) and p53 genes appear to play an important role in
      controlling cell division, and mutations in Rb-1 and p53 have been reported
      widely in non-gynecological cancers. Unlike other cancer-related genes, which
      become activated during carcinogenesis, it is the loss of wild type p53 and
      Retinoblastoma protein (RB) function that is thought to contribute to cancer
      development. These genes therefore, have been called tumor suppressor genes since
      normal function appears to be necessary for negative control of cell growth.
      Several viral oncoproteins have been shown to interact with RB and p53. It seems
      likely that the formation of these complexes inactivates the cellular protein
      resulting in an overall effect similar to somatic mutation of the Rb-1 or p53
      genes. The HPV16 transforming proteins E7 and E6 complex with protein products of
      Rb-1 and p53, respectively. In HPV positive anal and cervical tumors the normal
      function of RB and p53 may be inhibited by these viral proteins and so mutation
      within the RB-1 and p53 gene coding sequences would not appear to be a necessary
      step in the genesis of these tumors. However, in HPV negative tumors from the
      same tissues, loss of wild type Rb-1 and p53 activity may only be achieved by
      somatic mutation of these genes.

PMID- 11576228
TI  - Murine gammaherpesvirus-68-induced interleukin-10 increases viral burden, but
      limits virus-induced splenomegaly and leukocytosis.
AB  - Based on its genomic sequence and its pathogenesis, murine gammaherpesvirus-68
      (gammaHV-68) has been established as a tractable model for the study of viral
      infections caused by the human gammaherpesviruses, Epstein-Barr virus or human
      herpesvirus-8. Despite significant advances, the mechanisms responsible for
      gammaHV-68-induced alterations in the protective host response, and the
      accompanying virus-induced leukocytosis, are not clear. In the present study, we
      questioned whether viral infection resulted in endogenous interleukin-10 (IL-10)
      production that might alter the host response. Infection of C57BL/6 mice resulted
      in increased IL-10 expression, demonstrating that gammaHV-68 could induce
      endogenous production of this cytokine. Infected C57BL/6 mice demonstrated the
      characteristic splenomegaly associated with this viral infection, however, we
      were surprised to discover that the splenomegaly was greater in syngeneic mice
      genetically deficient in IL-10 (IL-10-/-). These results strongly suggested that
      endogenously produced IL-10 might serve to limit leukocytosis in wild-type mice.
      Quantification of viral burden demonstrated a significant elevation in C57BL/6
      versus IL-10-/- mice, with increases in virus being observed in both the
      macrophage and B-lymphocyte populations. The decreased viral load in syngeneic IL
      10-/- mice correlated with an increased expression of endogenous IL-12,
      suggesting a mechanism of protection that was IL-12 dependent. Taken together,
      these studies demonstrate a surprising dichotomy for endogenous IL-10 production
      during gammaHV-68 infection. While the lack of IL-10 results in increased IL-12
      expression and a lower viral burden, IL-10-/- mice also experience an increased
      leukocytosis.

PMID- 11576230
TI  - Carcinoma of the endometrium in Norway: a histopathological and prognostic survey
      of a total population.
AB  - In a histopathological review of a total population, 1974 cases of endometrial
      carcinoma were found from 1970 to 1977. Of these 1566 (79.3%) were
      adenocarcinomas of the endometrioid type, 181 (9.2%) adenoacanthomas, 97 (4.9%)
      clear cell carcinomas, 74 (3.7%) adenosquamous carcinomas, 31 (1.6%)
      undifferentiated carcinomas, 22 (1.1%) serous papillary carcinomas and 3 (0.1%)
      squamous cell carcinomas. Thirty percent of the tumors were well differentiated,
      44% moderately and 25.9% poorly differentiated. The mean age at diagnosis was
      62.0 years (range 32-93 years). Age was clearly related to histologic type, grade
      and extent of myometrial infiltration. Crude 5- and 10-year survival rates for
      the entire group were 73.1 and 61%. For the different subtypes of endometrial
      carcinoma the 5- and 10-year crude survival rates were as follows: adenoacanthoma
      91.2 and 79.6%, adenocarcinoma of the endometrioid type 74.1 and 62.2%,
      adenosquamous carcinoma 64.9 and 52.7%, undifferentiated carcinoma 58 and 48%,
      clear cell carcinoma 42.3 and 30.9% and serous papillary carcinoma 27 and 14%.
      All three patients with squamous cell carcinoma died within a year. The 5- and 10
      year survival rates were 87.8 and 79.7% for grade 1 tumors, 76.6 and 62.1% for
      grade 2, and 60.1 and 48.6% for grade 3. The extent of myometrial infiltration
      was a string predictor of prognosis. The 5- and 10-year survival rates of
      patients with intramucosal tumors and tumors infiltrating the inner half of the
      myometrium were, respectively 89.6 and 82.5%, and 84.7 and 72.7%. Only 48.3 and
      29.3% of the patients with tumors reaching the serosa survived, respectively 5
      and 10 years. Patients without demonstrable vessel invasion had a significantly
      better prognosis than those with vessel invasion with a survival rate of 83.5 and
      61.1% at 5- and 10-years, compared with 64.5 and 53.8%, respectively. Age at the
      time of diagnosis was an important prognostic factor for crude survival. Surgico
      pathological staging was significantly better than clinical staging in predicting
      prognosis only in advanced stages.

PMID- 11576231
TI  - Radioimmunotargeting in ovarian carcinoma patients with indium-111 labeled
      monoclonal antibody OV-TL 3 F(ab')2: pharmacokinetics, tissue distribution, and
      tumor imaging.
AB  - Safety and feasibility of tumor targeting with radiolabeled monoclonal antibodies
      was studied in 28 patients suspected of having ovarian carcinoma, after i.v.
      administration of 1 mg F(ab')2 fragments of the murine monoclonal antibody OV-TL
      3, labeled with 150 MBq Indium-111. There were no adverse reactions,
      hematological and biochemical serum parameters were stable. In one patient a
      (subclinical) HAMA-response was found. Plasma clearance of the immunoconjugate
      was biphasic with half lives of t(1/2)}alpha = 1.4+/-0.8 h and t(1/2)}beta =
      25.1+/-3.7 h, resulting in an optimal time period for immunoscintigraphy at 24-48
      h after administration. In 20 patients, undergoing extensive explorative surgery,
      a total of 271 samples of tumorous and normal tissues were analyzed for
      radiolabel uptake and tumor presence. The mean uptake in tumor deposits was 5.6
      times (range 2.2-19.3) as high as the uptake in normal tissues (fat, peritoneum,
      muscle, skin). The diagnostic accuracy of immunosctigraphy was compared with that
      obtained with computer tomography, magnetic resonance imaging, ultrasonography
      and physical examination. While pelvic localizations were equally well detected
      by all methods, 48% of the abdominally located tumor deposits were correctly
      diagnosed by immunoscintigraphy, with only 12% detected by ultrasonography, 8% by
      CT-scanning and physical examination, and 6% by MRI. Immunoscintigraphy has
      potential as a diagnostic tool in ovarian cancer patients and biolocalization
      results justify further research into the therapeutic application of labeled
      monoclonal antibodies.

PMID- 11576232
TI  - A phase II trial of intravenous etoposide (VP-16-213) in epithelial ovarian
      cancer resistant to cisplatin or carboplatin: clinical and serological evidence
      of activity.
AB  - Etoposide (VP16) was administered intravenously at a dose of 150 mg/m2 daily for
      2 days every 2 weeks to 24 patients with progressing epithelial ovarian carcinoma
      which was resistant to platinum analogues. Using standard response criteria there
      were five clinical partial responses (21%, 95% confidence limits 5-37%) and three
      disease stabilizations. However, the aim of our study was to determine if
      etoposide was non-cross-resistant with platinum analogues and therefore we also
      developed additional response criteria based on serial CA 125 levels. This was to
      enable us to differentiate within the heterogeneous group of responses that form
      the stable disease category. Nine of 23 patients (39%, 95% confidence limits 19
      59%) demonstrated a fall (all rising prior to etoposide) and of these, three had
      a serologic partial remission (65% or greater fall). The serologic and clinical
      responses were strongly correlated. Falling CA 125 levels occurred in the eight
      patients with either clinical partial responses or disease stabilizations.

PMID- 11576233
TI  - An in vitro study of ovarian atypical proliferating (borderline) serous tumors.
AB  - Seven human serous ovarian atypically proliferating tumors (tumors of borderline
      malignancy) were grown in primary culture and compared morphologically with
      established cell lines derived from serous carcinomas (stage III-IV). Several
      parameters were investigated in order to establish the place of these tumors in a
      neoplastic spectrum between benign and frankly malignant serous neoplasms. The
      atypically proliferating tumors showed serous features, including prominent
      microvilli and multiple cilia, similar to those found in the malignant serous
      cells. DNA flow cytometric studies of the atypically proliferating tumors showed
      them to be diploid. Keratins were strongly expressed immunohistochemically by all
      the atypically proliferating tumors. Vimentin was also detected in six of the
      original tumors but only in one primary culture. The capacity to culture and
      study cells which represent possible intermediate stages in the evolution of
      ovarian malignancy may prove useful as an in vitro model for this disease.

PMID- 11576234
TI  - Cervical epithelial abnormalities among women with vulval warts-no more common
      than among controls.
AB  - Eighty-four women with vulval warts and 46 controls were examined for cervical
      epithelial abnormalities by cytology and colposcopy. The prevalence of
      colposcopically detected abnormalities was the same in the two groups. Minor
      cytologic abnormalities (less than moderate dyskaryosis) were more common among
      women with warts than among controls. It is concluded that women with vulval
      warts are no more likely than controls to have evidence of cervical epithelial
      abnormalities. These findings are discussed in the light of apparently
      contradictory findings by other workers.

PMID- 11576235
TI  - Regression of peritoneal leiomyomatosis after treatment with gonadotropin
      releasing hormone analogue.
AB  - A case of a 42-year-old woman with peritoneal leiomyomatosis (PL) unrelated to
      pregnancy or any other obvious hormonal source is presented. After treatment with
      leuprolide acetate for six months, a second-look operation revealed that the
      majority of the nodules totally regressed. The few remaining ones were
      substantially reduced in size and exhibited histopathologic evidence of fibrotic
      change. This response to treatment is documented here for the first time. Since
      this case was not associated with initial abnormally raised hormonal levels, the
      regression was caused solely by the treatment and not by the removal of any
      hormonal stimulus. The usefulness of GnRH analogues in the treatment of PL is
      proposed.

PMID- 11576236
TI  - 'Is there a role for adjuvant pelvic radiotherapy after radical hysterectomy in
      early stage cervical cancer?'

PMID- 11576237
TI  - Flow cytometric DNA analysis in gynecological oncology.
AB  - The relevance of flow cytometric DNA analysis in neoplasia of the female genital
      tract is reviewed. The virtues and limitations of the technique are discussed.
      There is good evidence, mainly from retrospective studies, that DNA ploidy and/or
      the tumor S-phase fraction are valuable prognostic indicators in patients with
      carcinoma of the ovary and endometrium. Further prospective studies are needed,
      however, to establish the precise value of flow cytometric DNA analysis before it
      can be used safely for stratification of therapeutic regimes.

PMID- 11576238
TI  - Relationship between epidermal growth factor receptor (EGF-R) and various
      prognostic factors in human endometrial carcinoma.
AB  - Eighty primary endometrial carcinomas were analyzed for the presence of epidermal
      growth factor receptors (EGF-R) by the use of a single point (1ng 125I-EGF) EGF-R
      assay. Fifty percent of the analyzed specimens were EGF-R positive (EGF-R(+))
      with binding capacities > 1 fmol mg-1 and 15% bound > 7 fmol mg-1. The EGF-R
      status was correlated with different clinically relevant prognostic factors and
      the survival rates were analyzed. The correlations revealed no significant
      differences in the grade of tumor differentiation and in the depth of myometrial
      invasion. The advanced tumor stages III and IV and tumors with a squamous cell
      component in the histologic examination expressed EGF-R in a higher percentage.
      Between the EGF-R and the steroid receptor status existed a weak negative
      correlation. Estrogen receptor positive tumors were in 47% and progesterone
      receptor positive tumors in 45% EGF-R (+). The corresponding number for the
      receptor negative tumors were 57 and 65%. Life table analyses were performed with
      different cut-off limits for specific EGF binding ranging from > 1, > 3, > 5 and
      > 7 fmol mg-1. Dependent on the cut-off limits the analysis demonstrates a
      reduced survival probability for patients with EGF-R+ tumors. These differences
      were mainly found in the small group with a high number of EGF-R's (> 7 fmol).
      The analysis of tissue extracts for the presence of factors binding to the EGF-R
      revealed in some specimens high concentrations of EGF-like factors. By the use of
      TGFa (transforming growth factor alpha) immunohistochemistry we were able to
      demonstrate that the tumor cells produce TGFa, whereas the stroma is TGFa
      negative. We assume that the EGF-like factors consist mainly of TGFa.

PMID- 11576239
TI  - A scoring system for predicting recurrence of cervical cancer.
AB  - An evaluation was made of factors that affect the recurrence of cervical cancer
      after primary surgery, these including age, clinical stage, histology, grade,
      involvement of uterine body, parametrium or vagina and lymph node metastases.
      During a period of at least 3 years, 702 of 1508 patients who underwent radical
      hysterectomy and pelvic lymph node dissection were studied by using a scoring
      system. A comparison between the group of women scored at or greater than 13 that
      scored less than 13 revealed that the risk of recurrence was higher in the former
      group. One hundred and twenty five of 702 patients found to have positive pelvic
      node involvement scored greater than 13, which rendered them eligible for further
      mangement as follows: the recurrence rate in 99 patients receiving multi-agent
      chemotherapy was 34.4%, compared with 65.4% in 26 patients receiving no treatment
      (P < 0.01). Applying this score to other patients in planning adjuvant therapy,
      the recurrence rate may be reduced further. The number of patients needlessly
      exposed to the toxic effects of multi-agent chemotherapy may be reduced also.

PMID- 11576240
TI  - Cervical carcinoma: a hazard model in early stage disease.
AB  - The 235 patients with stage IB/IIA cervical carcinoma treated by Wertheim's
      hysterectomy, as a primary procedure, at St Mary's Hospital, Manchester between
      1975 and 1989 inclusive, form the basis of this study. Using Cox's regression
      model, four variables were shown to have independent prognostic significance.
      These were: (1) lymphatic permeation (adjacent to the tumor); (2) tumor volume;
      (3) being pregnant at diagnosis and (4) lymph node metastases. A heuristic model
      was formulated which was based upon these four factors and by using this
      information it was possible to separate the patients into four distinct
      prognostic groups. It is suggested that this model may prove useful in
      identifying those patients at a higher risk of dying of disease and who would
      benefit from early adjuvant systemic therapy.

PMID- 11576241
TI  - Patients with squamous cell versus adeno(squamous) carcinoma of the cervix, what
      factors determine the prognosis?
AB  - Patients with squamous cell carcinoma of the cervix FIGO stages IB to IV (n =
      306) were compared to patients with adeno(squamous) carcinoma (n = 70). There was
      no difference between the mean ages of the groups. In the patients who underwent
      radical surgical treatment, whether or not in combination with radiotherapy (n =
      209), stepwise regression analysis showed that a positive lymph node status was
      the most unfavorable prognostic factor, followed by the histologic type
      (adeno(squamous) carcinoma) and the tumor diameter (> 3 cm). Vascular-space
      invasion had no additional prognostic value. Patient's age did not affect the
      prognosis. Distant metastases were not found to be more prevalent in the patients
      with adeno(squamous) carcinoma. In patients with adeno(squamous) carcinoma and
      positive lymph nodes, it is worth considering more intensive locoregional
      treatment than is usually prescribed for these patients and/or adjunctive
      chemotherapy, because there is a high risk of tumor recurrence.

PMID- 11576242
TI  - A cervical smear review in women developing cervical carcinoma with particular
      reference to age, false negative cytology and the histologic type of the
      carcinoma.
AB  - A review of all available cervical smears from 96 women who subsequently
      developed invasive cervical carcinoma was undertaken. The aim of the study was to
      determine the incidence of confirmed negative smears prior to the histologic
      diagnosis of carcinoma and investigate the relationship between the duration and
      grade of smear abnormality, the patients' age and the histologic types of
      cervical carcinoma. The results indicate that only 10% of women had confirmed
      negative smears, the majority occurring more than 7 years before the diagnosis of
      carcinoma. In contrast, 89% of young women (under 40 years of age) had a
      significant abnormality (moderate dyskaryosis or worse) up to 6 years before
      diagnosis. There is evidence to suggest that the preinvasive phase of cervical
      carcinoma may be shorter in younger women and that the less common types of
      cervical carcinoma occur more frequently in this group. The combination of
      inadequate clinical follow up and false negative cytology may have allowed a
      significant proportion of these women to develop invasive cervical carcinoma.
      Possible reasons for false negative smears have been identified and methods aimed
      at decreasing their frequency are discussed.

PMID- 11576243
TI  - Characterization of an estradiol-independent but estradiol-responsive growth
      phenotype in a human endometrial adenocarcinoma heterotransplanted into nude
      mice.
AB  - The tumor growth phenotype was characterized in relation to concentration of
      circulating estradiol, estradiol receptor (ER) activation and progesterone
      receptor (PgR) induction. Ten tumor pieces from an ER and PgR positive human
      endometrial adenocarcinoma grown in non-oophorectomized nude mice for one year
      were randomly selected to grow during a preparation phase of 4 weeks either in
      oophorectomized nude mice - to adapt tumor growth to the absence of estradiol
      (group A), or in non-oophorectomized nude mice (group B). For the experimental
      phase, tumor pieces from each group were again randomly assigned to either of two
      subgroups (i.e., 4 subgroups in all): with estradiol treatment (subgroups A+ and
      B+), or without (subgroups A- and B-) as control subgroups. There were no
      differences in take rate or tumor growth rate between the control subgroups (A-
      vs. B-), indicating tumor growth to be estradiol-independent. The tumor was
      estradiol-sensitive, however, as tumor growth could be stimulated by estradiol.
      Despite its estradiol-independence of growth, the tumor's estradiol-binding
      capacity varied according to whether the host animals were oophorectomized or
      not; and despite the similar growth patterns during the experimental phase, the
      values of high affinty bound ER (ER activation) were greater for tumors grown in
      non-oophorectomized mice during the preparation phase than for those grown in
      oophorectomized mice. Thus, our findings show that an ovarain (estradiol)
      independent but responsive phenotype of tumor growth is present in human
      endometrial adenocarcinomas growing in nude mice. This growth phenotype may
      represent an intermediate state of tumor progression to hormone independence and
      resistance, which has hitherto been observed only in rodent tumors.

PMID- 11576244
TI  - Low complication rate during intraperitoneal therapy through a totally implanted
      peritoneal access port in patients with ovarian cancer.
AB  - Fifty-three patients with histologically proven ovarian cancer were treated with
      intraperitoneally administered cisplatin or human recombinant interferon-alpha
      through a totally implanted peritoneal access port. A total of 281 treatment
      courses were given. No complications related to surgical implantation of the port
      were seen. Infectious complications, intra-abdominal problems or subcutaneous
      drug extravasation did not occur. In two patients the number of treatment courses
      was limited due to inflow obstruction. A totally implanted peritoneal access port
      proves to be a reliable route for the intraperitoneal treatment of patients with
      ovarian cancer. The strict aseptic technique we used contributes to its safety by
      preventing intra-abdominal infections.

PMID- 11576245
TI  - Operative staging and conservative surgery in the management of low malignant
      potential ovarian tumors.
AB  - The medical records of 45- patients with intraoperative diagnosis of borderline
      or low malignant potential (LMP) ovarian tumor were reviewed to identify factors
      affecting intraoperative management. The correlation between gross and histologic
      staging was examined, as was the complication rate following surgery. Patient age
      and presence of qualifying pathologic terms on frozen section diagnosis were the
      only important factors relating to performance of surgical procedure. Surgical
      complications were closely associated with non-conservative surgery. Thirteen of
      14 (92.8%) patients with significant complications had a hysterectomy. These 14
      patients had staging procedures at essentially the same rate as the entire
      population. Thirteen of 45 patients (28.8%) thought to have LMP by frozen section
      had a different diagnosis on permanent review; 5 were benign and 8 were frankly
      malignant, confirming the limitations of frozen section in the diagnosis of LMP
      ovarian tumor. Of 40 with LMP or frankly malignant tumors 5(12.5%) were upstaged
      based on unsuspected histopathologic findings. These results indicate the need
      for a standard approach to staging in patients who are suspected to have an LMP
      ovarian tumor and should encourage the performance of conservative surgery when
      appropriate.

PMID- 11576246
TI  - Preoperative discrimination between ovarian carcinoma, non-ovarian gynecological
      malignancy and benign adnexal masses using serum levels of CA125 and the
      polymorphic epithelial mucin antigens CASA, OSA and MSA.
AB  - Serum levels of the tumor associated antigens CA125, CASA, OSA and MSA were
      determined preoperatively in a non-consecutive series of patients with: invasive
      epithelial ovarian cancer (OC, n = 87), ovarian tumors of low malignant potential
      (LMP, n = 9), benign adnexal masses (BAM, n = 48) and other peritoneal and pelvic
      malignancies (n = 48). In addition, serum levels of CASA, OSA, and MSA were
      determined in 3477 asymptomatic well women. Ninety-eight percent of the
      asymptomatic women had CASA levels < 6.0 U ml-1, OSA levels < 5.5 U ml-1 and MSA
      levels < 80.0 U ml-1. Serum CA125 levels were> 35 U ml-1 in 89% of OC, in 44% of
      LMP, and in 23% of BAM. Serum CASA levels were> 6.0 U ml-1 in 58% of OC, in 0% of
      LMP, and in 0% of BAM. Serum OSA levels were> 5.5 U ml-1 in 61% of OC in 0% of
      LMP and in 4% of BAM. Serum MSA levels were> 80.0 U ml-1 in 56% of OC, in 11% of
      LMP, and in 10% of BAM. When cut-off levels were set to exclude all patients with
      BAM, the best discrimination from OC using a single assay was achieved using CASA
      (58%). However, a combination of CASA and CA125 gave positive levels in 69% of OC
      at levels which precluded BAM. All markers were also elevated in some colon
      cancers, cervical cancers, uterine cancers and other peritoneal malignancies. A
      combination of CA125 and CASA levels, obtained preoperatively may assist the
      general gynecologist in avoiding potentially difficult oncologic surgery.

PMID- 11576247
TI  - The impact of loop diathermy on management of early invasive cervical cancer.
AB  - Large loop excision of the transformation zone (LLETZ) allows complete histologic
      assessment of cervical neoplasia. However, selective colposcopically directed
      punch biopsy followed by local ablation allows the possibility of inappropriate
      local ablation of early invasive lesions missed at punch biopsy. The onus of
      accurate diagnosis lies on the colposcopist. We have studied 1143 patients
      managed with loop diathermy and identified 35 invasive squamous carcinomas and 9
      invasive adenocarcinomas. The data show that the cut-off for accurate colposcopic
      detection of invasive squamous lesions is not breach of the basement membrane but
      invasion up to a depth of 1 mm. On the other hand, colposcopy is an unreliable
      guide for the diagnosis of early adenocarcinoma. Diagnosis based on loop excision
      allows accurate, rational individualization of management for the unexpected
      diagnosis of colposcopically occult early invasive disease whilst retaining the
      logistic benefits of a 'see and treat' policy.

PMID- 11576248
TI  - Investigation of the c-neu proto-oncogene related protein, p185, in the serum of
      primary epithelial ovarian cancer patients.
AB  - The relatively high incidence of amplification and overexpression of the neu (c
      erb B2/HER-2) oncogene in breast cancer, and its association with poor prognosis,
      particularly in node negative patients, may allow identification of patients who
      require aggressive therapy to prevent an early relapse. It's association with
      ovarian cancer, however, is less well defined than in breast cancer. An ELISA for
      the c-neu proto-oncogene related protein, p185, has been developed recently using
      the monoclonal antibodies NB3 and TA1. In the first study of it's kind, we
      assayed serum samples from patients with primary epithelial ovarian cancer for
      circulating c-neu p185. Elevated levels were found in 21/178 (11.8%) patients. No
      correlation was found between serum levels and either the presence or volume of
      tumor, when assessed either after primary or at second-look surgery. A change in
      c-neu p185 levels did not correlate with response to chemotherapy. When subjected
      to univariate and multivariate analyses together with other known prognostic
      factors, serum c-neu p185 was not a significant predictor of progression-free
      survival or overall survival. Although c-neu p185 may be involved in the
      pathogenesis of ovarian cancer, it's assay in serum has no value in prognosis or
      monitoring.

PMID- 11576249
TI  - Nuclear volume and prognosis in ovarian cancer.
AB  - The prognostic value of the volume-weighted mean nuclear volume (MNV) was
      investigated retrospectively in 100 ovarian cancer patients with FIGO-stage IB-II
      (n = 51) and stage III-IV (n = 49) serous tumors. No association was demonstrated
      between the MNV and the survival or between the MNV and two of five additional
      parameters: age and amount of residual tumor. However, both in stage IB-II and
      stage III-IV carcinomas, the MNV increased significantly with increasing tumor
      grade and DNA-index. Furthermore, FIGO-stage IB-II patients had significantly
      smaller nuclei than patients with stage III-IV disease.

PMID- 11576250
TI  - Synergistic cytotoxic effects of recombinant human tumor necrosis factor and
      Etoposide (VP16) or Doxorubicin on A2774 human epithelial ovarian cancer cell
      line.
AB  - Recombinant human tumor necrosis factor (rHuTNF) is a cytokine, with some
      antitumor activity, released by stimulated monocytes-macrophages. In vivo and in
      vitro cytotoxicity studies testing the effectiveness of rHuTNF alone or in
      combination with chemotherapeutic agents have been carried out. We have evaluated
      the direct cytotoxic effect of rHuTNF on a human epithelial ovarian cancer cell
      line in vitro (A2774), alone or in combination with Etoposide (VP16) or
      Doxorubicin (Doxo), some topoisomerase II (Topo II) targeted drugs, or in
      combination with Cisplatin (CDDP), a not Topo II interactive drug. Our results
      suggest that rHuTNF is directly cytotoxic and that it is also able to induce a
      potentiation of VP16- or Doxo-cytotoxicity, but it is unable to potentiate CDDP
      cytotoxicity. These data represent a reasonable basis for combining rHuTNF with
      Topo II inhibitors within phase I studies. The combination regimen could be
      tested in ovarian cancer patients.

PMID- 11576251
TI  - Signet-ring cells in squamous cell carcinoma of the cervix and in non-neoplastic
      ectocervical epithelium.
AB  - Two cases of cervical carcinoma and two cases of normal ectocervical epithelium
      with a squamous signet-ring cell component are presented. In one carcinoma the
      vacuolization was so prominent that it partially obliterated the epithelial
      pattern of the tumor. Paraffin specimens were studied with a panel of histo- and
      immunohistochemical stains and by electron microscopy. The vacuoles of the
      squamous signet-ring cells did not contain glycogen, mucopolysaccharides or
      masses of intermediate filaments. The findings are discussed in relation to
      possible human papillomavirus and Chlamydia trachomatis infection. The true
      nature and possible clinicopathologic implications of the squamous carcinoma with
      signet-ring cells remain to be established, but the phenomenon may cause
      diagnostic difficulties, especially in biopsy specimens.

PMID- 11576252
TI  - A stage Ia vulvar carcinoma with an inguinal lymph node recurrence after local
      excision. A case report and literature review.
AB  - A patient with a stage Ia vulvar squamous cell carcinoma (< 1 mm invasion) is
      reported in which an inguinal recurrence one and a half years after partial
      radical vulvectomy and superficial inguinal lymph node sampling was noted. After
      the initial biopsy showing a tumor invading 0.3 mm into the stroma, residual
      tumor could not be shown in the vulvectomy specimen nor in the superficial lymph
      nodes. A review of the literature indicates that this is only the second reported
      case of stage Ia vulvar carcinoma with lymph node metastases.

PMID- 11576254
TI  - Lactic acidosis and hypoglycemia: a metabolic complication of advanced
      gynecologic malignancy.
AB  - Refractory lactic acidosis and hypoglycemia characterize a paraneoplastic
      syndrome observed in advanced gynecologic cancer, as illustrated by a patient
      with a large malignant mixed Mullerian tumor. Massive infusions of sodium
      bicarbonate and glucose failed to reverse her metabolic abnormalities, and the
      patient suffered a rapidly fatal course. The biochemical basis for this metabolic
      complication is reviewed, including how medical intervention can lead to
      iatrogenic exacerbation of the metabolic imbalance.

PMID- 11576253
TI  - Goserelin a GnRH-analogue as third-line therapy of refractory epithelial ovarian
      cancer.
AB  - Between October 1988 and March 1991, 23 ovarian cancer patients with progressive
      disease whilst receiving second- or third-line polychemotherapy received
      subcutaneously 3.6 mg Goserelin, a GnRH analogue, at monthly intervals until
      further tumor progression. Four patients (17.4%) achieved partial response, 7
      patients (30.4%) had stable disease and 12 patients (52.2%) showed further tumor
      progression. Median time to tumor progression was 8.5, 5.3 and 2.1 months,
      respectively (Mantel test, P = 0.0003). Ten out of 11 patients who showed partial
      response or no change had grade 2 or grade 3 tumors. We conclude that Goserelin
      shows evidence of antitumor activity also in grade 2 and grade 3 ovarian
      carcinoma. It offers a therapeutic alternative to a group of patients, in whom we
      usually terminate cytotoxic treatment.

PMID- 11576255
TI  - Flow cytometric DNA measurements in squamous cell carcinoma of the vulva: an
      important prognostic method.
AB  - One hundred and thirty-one squamous cell carcinomas of the vulva were examined by
      FCM-DNA measurements. Samples were prepared from paraffin-embedded tissue. Of
      these, 66 were found to be diploid, 52 aneuploid and 13 could not be evaluated.
      The 5-year crude survival rate was 62% for the diploid and 23% for the aneuploid
      tumors (P < 0.001). The aneuploid tumors without lymph node (LN) metastases
      showed a 5-year cancer-related survival rate of 44% as compared to 58% for the
      diploid tumors with LN metastases. In a multivariate Cox regression analysis the
      most important independent prognostic parameters were (1) LN involvement (P <
      0.0001), (2) tumor ploidy (P = 0.0001) and (3) tumor size (P = 0.0039). By using
      ploidy and lymph node involvement in this way as prognostic factors we are able
      to identify high- and low-risk groups of patients. We strongly believe that these
      results should lead to a different attitude towards therapy in vulva cancer
      patients.

PMID- 11576256
TI  - Outpatient management of malignant ascites using ultrasound, a trocar, and a
      Tenckhoff catheter.
AB  - The Tenckhoff catheter provides useful access to the peritoneal cavity for
      chronic peritoneal dialysis and treatment of intraperitoneal malignancy. The
      usual methods of placement of Tenckhoff catheters include: blind insertion, open
      surgical implantation and peritoneoscopic guided placement. This is a description
      of a technique for percutaneous introduction using a trocar. Sonographic guidance
      is used to assure a safe insertion and proper location. This technique has been
      used in the office to provide access to the peritoneal cavity to allow palliative
      management of massive, intractable malignant ascites. The patient or selected
      caretaker can care for and access the catheter intermittently at home for relief
      of symptoms.

PMID- 11576257
TI  - Symptomatology, localization and treatment of recurrent cervical carcinoma.
AB  - In a group of 367 women treated for invasive carcinoma of the cervix tumor
      recurrence was discovered at an asymptomatic stage in 16 (23%) patients. The
      tumor recurrence was localized to the pelvis in 29 (41%) cases, in the vaginal
      wall in 3 (4%) cases, and 39 (55%) patients had distant metastases (with or
      without recurrent tumor in the pelvis). Curative treatment (surgery, n = 2;
      radiotherapy, n = 8) was applied in 5/29 (17%) patients whose recurrent disease
      was confined to the pelvis, in all 3 patients with vaginal recurrence and in 2/39
      (5%) of the patients with distant metastases. Permanent remission (follow-up > 36
      months) was observed in 2 patients with vaginal recurrence and in one with
      central recurrence. Temporary complete remission (mean 22 months, range 12-30
      months) was observed in 3 patients (2 with central recurrence and one with
      vaginal recurrence). In 20 (69%) of the patients with central or locoregional
      recurrence, the primary treatment had been so radical (including adjuvant
      postoperative or full radiotherapy) that surgical treatment or radiotherapy of
      the recurrence was not considered possible or worthwhile; moreover, 4 of the
      patients were older than 80 years of age. In retrospect, exenterative treatment
      could have been considered in 14 patients (< 70 years) and based on 50%
      operability, could have led to a cure in 2 to 4 patients with tumor recurrence in
      the pelvis without distant metastases. Chemotherapy was applied to 10 patients,
      one of whom went into complete remission of lung metastases (follow-up 108
      months).

PMID- 11576258
TI  - Epithelial ovarian tumors of borderline malignancy: a study of 50 cases.
AB  - Of 50 patients with borderline epithelial ovarian tumors, 32 (64%) had serous, 17
      (34%) had mucinous and one (2%) had endometrioid tumor. All patients with
      mucinous tumor had stage I disease, whereas 4 patients with serous tumor had
      stage II-III disease. Five patients (10%) were pregnant at the time of diagnosis.
      Seventeen patients (34%) had initial surgery with ovarian conservation and 7 of
      them were not subjected to further surgery. Five patients (10%) received adjuvant
      chemotherapy. Five-year survival and 5-year disease-free survival rates were 100%
      and 96.4%, respectively. It is concluded that for patients with stage IA disease
      unilateral salpingo-oophorectomy seems to be adequate treatment and for those
      with more than stage IA disease, surgery should include total abdominal
      hysterectomy and bilateral salpingo-oophorectomy. Although the effectiveness of
      chemotherapy in these tumors is uncertain, adjuvant chemotherapy is advocated for
      patients in whom spread of the tumor beyond the ovaries has occurred.

PMID- 11576259
TI  - Nuclear morphometry: a strong prognostic factor for survival after secondary
      surgery in advanced ovarian cancer.
AB  - Nuclear morphometry was performed on the diagnostic biopsy in 65 cases of non
      mucinous ovarian carcinoma (FIGO stage IIB-IV) and its prognostic value regarding
      patient survival after the second-look operation was compared to that of
      morphology and clinical observations. In a univariate Cox survival analysis four
      morphometric factors were found to be significant predictors of survival (the
      standard deviations (SD) of the nuclear area, perimeter, largest perpendicular
      axis, and largest axis). Age, the size of residual tumor after the primary
      operation, and a combined variable describing the status at the second-look
      operation and also the result of tumor reduction were significant clinical
      variables. None of the morphologic variables proved to be significant. In the
      multivariate Cox analysis the SD of the largest perpendicular nuclear axis gave
      independent prognostic information together with either the size of residual
      tumor after the primary laparotomy (P = 0.00004) or the second-look variable (P <
      0.00001). When the SD of the largest perpendicular nuclear axis and the second
      look variables were included in the model the size of residual tumor after the
      primary operation added no further prognostic information. We conclude that
      nuclear morphometry is a simple, easily implemented and cheap quantitative method
      which gives objective and valuable prognostic information regarding survival in
      advanced ovarian cancer.

PMID- 11576260
TI  - Carcinoma of the cervix-recurrences in Queensland 1982-1986.
AB  - A retrospective study of recurrent cancer of the cervix was carried out on
      patients who attended the Gynaecologic Oncology Unit, Royal Brisbane Hospital,
      between the years 1982 and 1986. Ninety-four recurrences were assessed out of 526
      patients (17.7%). The likely recurrence was related to stage. Sixty-seven percent
      had pelvic recurrences with 33% recurring in extrapelvic sites alone. The most
      common site of tumor recurrence was central pelvis (47%). Histopathology
      recurrences were analyzed and recurrence was found to be more common with the
      rare tumor types. Mortality of recurrent carcinoma of the cervix is high.
      Multivariate analysis shows lymph node metastases and histologic status of
      resection margins to be independent variables predictive of recurrence.
      Lymphvascular space involvement has not been an independent variable after
      adjusting for nodes and margins. Cytology of vaginal vault or residual cervix
      smear shows that 58% of patients with central recurrence had an abnormal smear.
      The relative literature was discussed in relation to the findings of our unit.

PMID- 11576261
TI  - A phase I/II study combining radical radiotherapy with concurrent cisplatin in
      the treatment of advanced squamous cell carcinoma of the cervix.
AB  - Sixteen patients with advanced cervix cancer have been treated in a phase I/II
      study of concurrent radiotherapy and cisplatin chemotherapy. The external beam
      radiotherapy was given as a 'split course' because of initial concerns about
      acute toxicity. The treatment was well tolerated with all patients completing the
      prescribed radiotherapy and all patients received the intended four doses of
      cisplatin. One of 5 patients with stage IVB disease is alive and disease free 35
      months after treatment. Six of the 11 patients with disease confined to the
      pelvis are alive and disease free between 28 and 53 months after treatment. One
      patient has required surgery for a recto-sigmoid stricture.

PMID- 11576262
TI  - Myxoid liposarcoma of the broad ligament.
AB  - A patient diagnosed as having a myxoid liposarcoma of the broad ligament is
      presented. She was treated with surgical resection and radiation therapy and is
      free of disease 2 years after completing surgery.

PMID- 11576263
TI  - The clinical significance of malignant peritoneal cytology in stage I endometrial
      carcinoma.
AB  - The prevalence of malignant peritoneal cytology in patients with International
      Federation of Obstetrics and Gynecology (1971) stage I endometrial carcinoma and
      its predictive value for recurrence of disease following hysterectomy were
      analyzed by numerically pooling the crude results of independent studies.
      Malignant cytology occurred in 8.3, 12.1 and 15.9% of patients with grade 1, 2
      and 3 histology, respectively, and in 7.6% and 17.2% of patients with superficial
      and deep myometrial invasion, respectively. Prevalence was heterogeneous in the
      groups with grade 1 histology, grade 2 histology and superficial invasion, and
      homogeneous in the groups with grade 3 histology and deep invasion. This,
      together with a technical false positive rate of approximately 5% in the
      diagnosis of malignant cytology, suggests that the pooled values of prevalence
      for the low grade and superficially invasive groups may be overestimated.
      Malignant cytology was strongly associated with disease recurrence (pooled odds
      ratio of 4.7 with a 95% confidence interval of 3.5-6.3). Qualitative review of
      the literature suggests that this is largely due to the association of malignant
      cytology with other adverse prognostic factors which dominate the clinical course
      of the disease. In the absence of other adverse prognostic factors, the true
      prevalence of malignant cytology is low. This limits the clinical utility of
      cytology as an independent predictor of either overall recurrence or site of
      recurrence. Routine adjuvant treatment of patients with malignant cytology is
      therefore not justified.

PMID- 11576264
TI  - Carboplatin with cyclophosphamide in patients with advanced ovarian cancer: an
      efficacy and quality-adjusted survival analysis.
AB  - The efficacy and toxicity of a combination of carboplatin and cyclophosphamide
      (CC) were studied in a group of 76 patients with advanced ovarian cancer.
      Progression-free (PFS) and overall survival were compared with a historical group
      of 65 patients treated with CAP-5 (cyclophosphamide, adriamycin, cisplatin).
      Subjective toxicity was compared by the measurement of TWiST, the Time Without
      Symptoms of Disease or Treatment. Of 75 evaluable patients treated with CC, 18
      (24%) had a pathologically complete remission (pCR), and 31 (41%) a partial
      remission (PR). CC led to leukopenia grade III in 38% and grade IV in 3% of 421
      treatment cycles. Thrombocytopenia grade III was seen after 7% and grade IV after
      2% of cycles. Treatment delay occurred in 11.5% and dose reduction in 21% of
      cycles. Nephro- or neurotoxicity did not occur. After a median follow-up of 18
      months, the median PFS was 24 months and the overall survival was 25 months.
      Median duration of TWiST was 22 versus 10 months after CAP-5 (P < 0.01). Compared
      with historical controls, treatment with CC is equivalent to CAP-5. It is free of
      nephro- and neurotoxicity, but is more myelosuppressive. Quality of life,
      measured by TWiST, is significantly better during CC. As a consequence of its
      equivalent efficacy, but lower subjective toxicity, carboplatin should replace
      cisplatin in treating patients with advanced ovarian cancer.

PMID- 11576265
TI  - A randomized trial comparing platinum-based chemotherapy followed by radiotherapy
      vs. radiotherapy alone in patients with locally advanced cervical cancer.
AB  - Seventy-one patients with stage IIb-IVa cervical cancer were entered on a
      randomized trial comparing standard pelvic radiotherapy vs. 3 cycles of
      combination chemotherapy with cisplatin, vinblastine and bleomycin followed by
      pelvic radiotherapy. Four out of 34 patients randomized to PVB followed by
      radiotherapy received no PVB and a further 3 patients had only one or 2 cycles of
      chemotherapy prior to radiotherapy due to drug-related toxicity or progressive
      disease. After a median follow-up of 3.1 years, no significant difference in
      survival has emerged between the two randomized groups. However, a difference in
      the pattern of relapse is emerging with a relatively reduced frequency of
      systemic relapse in patients receiving chemotherapy prior to local radiotherapy
      compared to radiotherapy alone. Tumor response was seen following PVB treatment
      and prior to radiotherapy in 47% of patients. Overall the tumor response rate
      following completion of radiotherapy was 89% in those treated by radiotherapy and
      94% after PVB+radiotherapy. Thirty-three percent of patients randomized to
      radiotherapy alone relapsed first at a distant (extra pelvic site), and only 18%
      of patients randomized to initial PVB followed by radiotherapy relapsed
      systemically initially. When results are presented according to treatment
      actually given, these trends in patterns of treatment failure are magnified. No
      treatment-related deaths were reported, and there was no excess of complications
      with pelvic radiotherapy in the group who had received prior PVB chemotherapy.

PMID- 11576266
TI  - Abdominopelvic computed tomography in the preoperative evaluation of suspected
      ovarian masses.
AB  - To evaluate the efficacy of computed tomography (CT) in 175 patients scheduled to
      undergo surgery for a suspected ovarian mass, we compared preoperative CT
      findings with the findings at surgery and histology. At surgery, 115 patients
      were found to have epithelial ovarian malignancies (20 stage 1, 7 stage II, 50
      stage III and 38 stage IV) while 60 had benign pelvic tumors. CT findings were
      suggestive of malignancy in 4 (7%) of 60 patients with benign tumors and
      suggestive of benign disease in 3 (3%) of 115 patients with malignant ovarian
      tumors; 30% of all scans were inconclusive. The sensitivity of CT for predicting
      pelvic or para-aortic lymph node involvement in 42 patients who underwent
      lymphadenectomy was 62 and 70%, respectively; the specificity was 100%. The
      results of this series suggest that the routine use of CT in the preoperative
      evaluation of patients does not seem justified.

PMID- 11576267
TI  - Clinical significance of endocervical curettage as part of colposcopic
      evaluation. A review.
AB  - This paper addresses the role of endocervical curettage (ECC) as an adjunct of
      colposcopic evaluation of patients with abnormal cervical cytology. In a meta
      analysis of literature data the contribution of ECC to the diagnostic accuracy of
      colposcopic examination and in the predictive value with regard to the final
      histologic diagnosis is discussed. The clinical impact of the application of ECC
      appears to be limited. Figures suggest a reduction in underdiagnosis of
      (micro)carcinoma in patients with satisfactory colposcopy and an increase of
      predictive value in diagnosis of invasive disease in unsatisfactory colposcopy.

PMID- 11576268
TI  - Immunohistochemical detection of CA-125 and carcinoembryonic antigen in ovarian
      tumors in relation to corresponding preoperative serum levels.
AB  - The immunohistochemically detectable expression of CA-125 and CEA in ovarian
      tumor tissue from 187 patients was related to corresponding preoperative serum
      levels. A strong positive association between tissue expression and the serum
      level of both the CA-125 and CEA antigens was found in cases of invasive
      epithelial ovarian carcinoma. However, this relationship was absent for CA-125 in
      borderline cases and patients with benign ovarian tumors, although the antigen
      frequently was detectable in them. The presence of ascites could be verified in 3
      of 10 cases with benign CA-125 negative tumors, but elevated CA-125 levels in
      serum. 'False negative' CA-125 levels were found in 6 borderline and 7 true
      invasive carcinoma cases despite positive tissue staining. Eight of those
      patients had limited stage I disease. The data suggests that although the tissue
      expression of the CA-125 and CEA antigens in invasive ovarian carcinoma has an
      important influence in the corresponding serum level, compartment barriers and
      low cell turnover in benign, and to a lesser extent borderline, cases result in
      low serum levels. In addition, other factors influence serum levels of CA-125,
      such as secondary peritoneal response with or without ascites, which may cause
      'falsely elevated' CA-125 results in benign disease.

PMID- 11576269
TI  - Tissue expression of CA-125 and carcinoembryonic antigen in ovarian carcinoma in
      relation to nuclear DNA content, histologic grade, and patient survival.
AB  - In a prospective study the immunohistochemically detectable tissue expression of
      the antigens CA-125 and CEA in 112 epithelial ovarian carcinomas and 23
      borderline tumors was related to histologic features of the tumor and to patient
      survival. The CA-125 antigen was expressed mainly in non-mucinous tumors, with no
      evident association between histologic grade and immunoreactivity. CEA was
      expressed in mucinous tumors regardless of tumor grade. Flow cytometric DNA
      analysis was performed on fresh frozen tissue in a subgroup of 60 cases. There
      was no association between DNA ploidy or S-phase fraction and the CA-125 or CEA
      antigen expression. Tumor stage, size of residual tumor masses after surgery and
      DNA ploidy had independent associations with patient survival in multivariate log
      rank analysis of prognostic factors. However, there was no association between
      the CA-125 or CEA antigen expression and patient survival. Thus, in ovarian
      carcinoma the expression of the CA-125 and CEA antigens seems to be independent
      of the inherent malignant potential of the tumor epithelium, while DNA analysis
      provides valuable prognostic information.

PMID- 11576270
TI  - Psychosexual functioning after treatment for gynecological cancer: an integrative
      model, review of determinant factors and clinical guidelines.
AB  - This review summarizes investigations dealing with the sexual functioning of
      women with gynecological cancer. A critical review of methods of investigation
      and results is presented and an outline for future research. The literature
      review is preceded by a short theoretical introduction on cancer and sexual
      behavior relevant to the conceptualization and assessment of sexual functioning
      under these circumstances. The review is concluded by some guidelines to help
      patients and partners cope with sexual problems after treatment of gynecological
      cancer. 

PMID- 11576271
TI  - Amplification of HER-2/neu oncogene in human ovarian cancer.
AB  - Amplification and/or increased expression of the HER-2/neu oncogene has been
      reported to occur in ovarian tumors and possibly to correlate with biologic
      behavior and prognosis. The frequency with which amplification is reported to
      occur is quite variable ranging from 0-30% in different series and this
      variability is probably accounted for by technical and methodologic factors. The
      variability and lack of reproducibility has raised questions about the usefulness
      of assessing amplification of the HER-2/neu oncogene and in particular its
      clinical relevance. In this study by using strict criteria for amplification and
      using multiple controls we could demonstrate unequivocal amplification of the HER
      2/neu oncogene by Southern blot analysis in only 11% of malignant ovarian tumors.
      The potential pitfalls with the techniques used to detect HER-2/neu oncogene
      amplification and overexpression are reviewed and possible ways to overcome some
      of the problems are suggested. 

PMID- 11576272
TI  - Primary treatment failure in patients with malignant ovarian germ cell neoplasms.
AB  - Between 1970 and 1990, 160 patients with malignant non-dysgerminomatous ovarian
      germ cell tumors have been treated at our own institution. Primary therapy failed
      in 42 of these patients, who constitute the basis for this study. Seventeen
      patients had stage I disease, 5 stage II, 17 stage III, and 3 stage IV.
      Histologic type included 13 immature teratomas, 8 endodermal sinus tumors, and 21
      mixed germ cell tumors. Primary therapy for 14 patients was surgery alone, for
      23, surgery plus chemotherapy, for 2, surgery plus radiotherapy and for 3, all
      three modalities. Median progression-free survival from initial diagnosis lasted
      6.8 months (range, 0.9-24 months). Thirty-four patients received chemotherapy as
      part of salvage; 5/11 (45%) who received VAC are disease-free, and 6/11 (55%) who
      received cisplatin combinations are disease-free. When primary VAC failed, 3/7
      (43%) were salvaged with cisplatin combinations. When primary cisplatin
      combinations failed, 2/5 (40%) were salvaged. Twelve of the 42 patients (29%) are
      currently alive disease-free. Primary treatment failure was attributed to surgery
      alone for 14 patients (7 because of misdiagnosis), radiotherapy for 5, and
      toxicity for 1. Of the 22 patients who failed chemotherapy, 12 did so because of
      a suboptimal regimen, 3 because of possible dose-intensity problems, one because
      of non-compliance, and 6 for unexplained reasons. Patients with ovarian germ cell
      tumors have an excellent probability of cure with aggressive primary therapy, but
      successful salvage may be difficult when primary treatment fails. 

PMID- 11576273
TI  - Novel, dose intensive, single-agent cisplatin in the first-line management of
      advanced stage ovarian cancer.
AB  - Cisplatin-based combination chemotherapy is the current standard chemotherapy for
      the management of advanced stage, epithelial ovarian cancer. However, correlation
      has been demonstrated previously between dose intensity and response for
      cisplatin, but not for the other cytotoxic drugs commonly used. We treated 46
      consecutive, newly diagnosed patients following standard debulking laparotomy
      with cisplatin 60 mg m-2 every 2 weeks for a total of 8 cycles. Survival and
      toxicity were compared with those of a similar cohort of 24 consecutive, newly
      diagnosed patients treated with cisplatin 75 mg m-2 plus cyclophosphamide 600 mg
      m-2 every 4 weeks for 6 cycles, at the same institution immediately prior to the
      current cohort. The single-agent cisplatin cohort received a mean relative
      cisplatin-equivalent dose intensity of 1.43 compared with a received mean
      relative cisplatin-equivalent dose intensity of 0.88 in the combination
      chemotherapy cohort, a 62.5% increase in the cisplatin dose intensity. At 2
      years, 69% of the patients receiving single-agent cisplatin were alive, compared
      with 38% of the group receiving the combination chemotherapy (P = 0.014).
      Alopecia (P < 0.00001) and myelosuppression (P < 0.0000001) were markedly less in
      the patient group receiving single-agent cisplatin. There was no significant
      difference in the incidence of neurotoxicity (P = 0.28) or nephrotoxicity (P =
      0.38) between the two patient groups. In summary, relatively dose intensive,
      single-agent cisplatin given in a biweekly schedule for the first-line management
      of advanced stage, ovarian cancer produced a survival advantage compared with the
      previous combination cyclophosphamide/platinum combination chemotherapy. This
      novel therapy takes one-third less time to complete and causes fewer side effects
      than the current standard of combination cyclophosphamide and cisplatin. 

PMID- 11576274
TI  - A new approach to the histologic study of ovarian tumors by analytical
      morphometry.
AB  - In recent years, borderline epithelial tumors of the ovary have been investigated
      by morphometric techniques to allow for a differential diagnosis from benign and
      malignant neoplasms. In order to enhance this discriminant power, we have applied
      a new analytical procedure to the evaluation of the nuclear shape in epithelial
      ovarian tumors. Sixty nuclei of benign ovarian serous neoplasms, 60 nuclei of
      serous borderline tumors and 60 nuclei of serous carcinomas (18 cases in all)
      were examined using the software system SAM (Shape Analytical Morphometry). The
      morphometric procedure consisted of three different phases: (i) extraction of
      nuclear fundamental curve: this is a function curve giving the smoothing of the
      original contour by two parametric equations (separately for x and y values as
      dependent variables); (ii) evaluation of nuclear contour irregularities by
      Fourier analysis; (iii) evaluation of nuclear shape asymmetry by SAE (Shape
      Asymmetry Evaluator): this is the ratio between the length of a segment of a
      parabola interpolating the original curve points and a straight line joining its
      extremities for a 180 degrees barycentric rotation according 10 degrees steps.
      All the obtained independent parameters were submitted to statistical analysis.
      Nuclei of borderline tumors showed dimensional parameters which were intermediate
      between those of benign and malignant tumors. Both the asymmetry and the
      irregularities of nuclear contour were greatest in carcinomas. 

PMID- 11576275
TI  - Human papillomavirus, Epstein-Barr virus, and cervical carcinoma in Greenland.
AB  - The incidence of cervical cancer in Greenland is one of the highest in the world.
      This is in accordance with known epidemiologic risk factors, in particular of
      sexual lifestyle and tobacco smoking. Yet a recent study of cervical smears from
      randomly selected Greenlandic women failed to demonstrate any elevated prevalence
      of human papillomavirus (HPV), of which particularly HPV types 16 and 18 are
      assumed to play a role in the development of cervical dysplasia and carcinoma.
      Another oncogenic virus, Epstein-Barr virus (EBV) is known to be widespread in
      the Greenlandic population and the virus has been reported to infect the female
      genital tract. We therefore used the polymerase chain reaction to examine
      paraffin-embedded tissues of cervical carcinomas from 11 indigenous Greenlandic
      women and, for comparison, also cervical carcinoma tissues from 11 Danish
      patients, for EBV, HPV 16 and HPV 18 DNA sequences. None of the 22 cervical
      tissues contained EBV DNA. Six Greenlandic and five Danish carcinomas harbored
      HPV 16 DNA, and one carcinoma of each group was HPV 18-positive. In conclusion,
      cervical carcinoma is not associated with EBV infection. Further, the oncogenic
      HPVs are probably encountered at the same rate in carcinomas from Greenland and
      from Denmark. 

PMID- 11576276
TI  - Cervical carcinoma after negative Pap smears: evidence against rapid-onset
      cancers.
AB  - Recently, suggestions have been made that a 'rapid-onset' type of cervical cancer
      is emerging. Evidence for this entity is based on the diagnosis of invasive
      cervical carcinoma within 2 or 3 years of a 'normal' Pap smear. Analysis of 237
      patients presenting to our unit between November 1986 and July 1990 with the
      histologic diagnosis of invasive carcinoma of the cervix revealed 51 patients
      (21.5%) who reported having had a 'normal' Pap smear within 2 years of diagnosis.
      Strenuous efforts were made to verify and retrieve these smears in an attempt to
      isolate a group of 'rapid-onset' cancers. Despite the patients' claim to the
      contrary, there was no record of a smear being performed in 15 patients (29%).
      The slides of six patients could not be located either due to lack of laboratory
      co-operation or because the slides had been destroyed: four of these patients had
      very early adenocarcinomas. The slides of 30 patients were retrieved and
      reviewed: 16 slides reported as negative contained cells consistent with either
      invasive carcinoma or carcinoma in-situ; four cases had virtually no cellular
      material on the slide; four cases contained atypical cells but requests for
      further material were not followed-up. Six patients had previously been treated
      for pre-invasive lesions over a range of 3-18 years. We found no case of invasive
      carcinoma in a patient with a confirmed adequate negative smear within 2 years of
      diagnosis. At most, six patients (2.52%) could have had 'rapid-onset' cancers but
      this could not be confirmed as these slides could not be reviewed. In summary,
      this study suggests that in our patient population, 'rapid-onset' cervical
      carcinoma is rare. 

PMID- 11576277
TI  - Carcinoma of the cervix: an analysis of prognostic factors, treatment and
      patterns of failure following Wertheims hysterectomy.
AB  - A clinicopathologic analysis of 70 patients treated by radiotherapy and/or
      chemotherapy following primary radical surgery has been undertaken. Clinical
      stage at presentation was IB (58 patients) and IIA (12 patients). Thirty-five
      patients (50%) had squamous carcinoma, 23 (33%) had adenosquamous carcinoma, 9
      (13%) had adenocarcinoma and 3 (4%) had an undifferentiated neoplasm. The reasons
      for further treatment were: (i) pelvic lymph node metastases (PLNM), 35 (50%);
      (ii) inadequate central clearance (ICC), 13 (18%); (iii) recurrent disease (RD),
      17 (24%); (iv) others, 5 (8%) cases. Sixty-seven patients had radiotherapy, one
      of whom also received adjuvant chemotherapy, three patients had chemotherapy
      alone, and 12 patients received chemotherapy for recurrence following
      radiotherapy. The 5-year survival in the above referral groups were: (i) 66%;
      (ii) 62%; (iii) 12%. The site of relapse following treatment was primarily pelvic
      in groups 2 (ICC) and 3 (RD) and extrapelvic in group 1 (PLNM). Of the histologic
      parameters studied the only factor of statistical significance in predicting
      outcome in this group who are recognized to have a generally poor prognosis was
      the presence of parametrial extension (P = 0.0066). Six cases (9%) developed
      complications following therapy, lymphoedema being the most common (66%). 

PMID- 11576278
TI  - Resolution of pulmonary metastases with chemotherapy in a patient with placental
      site trophoblastic tumor.
AB  - Placental site trophoblastic tumor (PSTT), a rare variant of gestational
      trophoblastic disease, was first described in 1976. PSTT is usually seen in young
      women, generally treated by hysterectomy, and is associated with a 20% fatality
      rate. The development of metastases secondary to PSTT is associated with an
      extremely poor prognosis. Metastatic PSTT has generally been resistant to
      chemotherapy although one complete and some partial responses have been noted
      previously. We report a case of a complete chemotherapeutic response in a patient
      with pulmonary metastases. 

PMID- 11576279
TI  - The incidence of persistent functioning endometrial tissue following successful
      radiotherapy for cervical carcinoma.
AB  - Sixty-three patients under the age of 50 years who were long-term survivors
      following radiotherapy for cervical cancer and had been placed on hormone
      replacement therapy (HRT) were identified. The median age at treatment was 37
      years and the mean delay from treatment to the initiation of HRT was over 15
      months. Fifteen of the 63 patients had experienced vaginal bleeding attributable
      to the effects of HRT on persisting endometrial tissue. The significance of this
      is discussed. 

PMID- 11576280
TI  - Organization of gynecological cancer care: a time for change.

PMID- 11576281
TI  - Tamoxifen and the female genital tract.
AB  - Ugwumadu AHN, Carmichael P, Neven P. Tamoxifen and the female genital tract. Int
      J Gynecol Cancer 1998; 8: 6-15. Tamoxifen was originally developed by Imperial
      Chemical Industries (England) (ICI) in 1966 as an anti-estrogenic contraceptive.
      Ironically, it found a role in the treatment of anovulatory infertility, but its
      most important application to date is in adjuvant hormonotherapy for breast
      cancer. Tamoxifen has a complex and poorly understood mix of estrogenic and anti
      estrogenic properties with variable and contrasting effects on hormone-sensitive
      target tissues, such as the endometrium. This article reviews the gynecologic
      lesions associated with tamoxifen therapy and discusses the merits and
      acceptability of endometrial surveillance tests and the role of progestogens.

PMID- 11576282
TI  - Survival of patients with primary fallopian tube carcinoma.
AB  - Vaughan MM, Evans BD, Weitzer MJ. Survival of patients with primary fallopian
      tube carcinoma. Int J Gynecol Cancer 1998; 8: 16-22. Thirty-seven patients with
      primary fallopian tube carcinoma (PFTC) presenting between 1952 and 1995 were
      studied. The mean age was 57 years. Seven patients had stage I disease, 20 stage
      II, 8 stage III, and 2 stage IV. Actuarial 5-year survivals were 73% for stage I,
      33% for stage II and 0% for stage III. Stage was a significant predictor of
      survival at 5 years (Stage I vs. III, P = 0.0006; stage II vs. III, P = 0.0001),
      however, the majority of patients, even with early stage disease, died of
      progressive PFTC within 10 years. Grade appeared highly significant at 5 and 10
      years (Grades 1 & 2 vs. 3, P = 0. 0023). Neither age nor lymphocytic infiltrate
      appeared definitely predictive of survival. Eleven of 22 stage II patients
      received adjuvant treatment. While their median and 5-year survivals were
      superior to those not receiving adjuvant treatment (51 vs. 30 months, 47% vs.
      22%), the difference was not statistically significant. This retrospective
      analysis confirms the poor prognosis of patients with PFTC. The majority of
      patients, even with early stage tumors, eventually succumb to their disease.
      Larger studies may identify a group of patients potentially curable with surgery
      alone, and clarify the role of adjuvant therapy.

PMID- 11576283
TI  - Prognostic factors in surgically treated stage IB-IIB carcinoma of the cervix
      with negative lymph nodes.
AB  - Comerci G, Bolger BS, Flannelly G, Maini M, de Barros Lopes A, Monaghan JM.
      Prognostic factors in surgically treated stage IB-IIB carcinoma of the cervix
      with negative lymph nodes. Int J Gynecol Cancer 1998; 8: 23-26. Two hundred and
      seventy-five females with stage IB-IIB negative lymph node cervical cancer,
      treated between January 1988 and December 1994 by radical hysterectomy and pelvic
      lymph node dissection, form the basis of this analysis. The clinical records were
      reviewed for all patients including histopathology, clinical features at
      presentation, and follow-up. Tumors were re-staged according to the 1995 FIGO
      classification. Median follow-up was 55 months and 85.8% were followed for longer
      than two years. There were 21 recurrences, 12 of which were true central
      recurrence (disease-free survival at 5 years: 91.66%). Fifteen of 25 deaths were
      due to cervical cancer (crude survival at 5 years: 93.27%). In univariate log
      rank analysis, stage (P = 0.005), tumor size (P = 0.0002), and lymph-vascular
      space involvement (LVSI) (P = 0.01) appeared to be statistically significant
      factors for tumor recurrence. Other factors including age, histology type,
      differentiation, adjacent cervical intraepithelial neoplasia or cervical
      glandular intraepithelial neoplasia, and presence of intraepithelial disease at
      resection margin were not found to be statistically significant. In multivariate
      analysis (Cox regression) tumor size (P = 0.02) and LVSI (P = 0.03) were the only
      independent variables. In the presence of negative lymph nodes and complete
      surgical excision, tumor size and LVSI are important predictors of local
      recurrence.

PMID- 11576284
TI  - The effects of the adenovirus-mediated wild-type p53 delivery in human epithelial
      ovarian cancer cell line in vitro and in vivo.
AB  - Hwang ES, Kim J, Kim JS, Kao C, Ko S-C, Chung L, Lee J-H. The effects of the
      adenovirus-mediated wild-type p53 delivery in human epithelial ovarian cancer
      cell lines in vitro and in vivo. Int J Gynecol Cancer 1998; 8: 27-36. The effect
      of p53 overexpression on the proliferation of various ovarian cancer cell lines
      was tested by using an adenovirus vector, Avp53, that expresses wild-type human
      p53. Cell lines SKOV3, 2774, and OVCAR3, which bear mutations in the endogenous
      p53 gene, were all affected by Avp53 treatment, undergoing growth suppression and
      apoptosis at a dose that had little effect on the growth of normal fibroblasts.
      In these cells, p21WAF1/CIP1 was readily induced and the hypophosphorylated pRb
      protein accumulated by the treatment of Avp53, suggesting that the growth
      inhibitory pathway can be activated in these cells by the expression of wild-type
      p53. However, in PA-1 cell line which endogenously expresses wild-type p53,
      p21WAF1/CIP1 was not induced by p53 transduction, although p53 was found
      transcriptionally active. These results indicate that the tested ovarian cancer
      cell lines bear defects either in p53 itself or in the responsiveness to p53. The
      cytocidal effect of Avp53 was also examined in vivo against tumors developed in
      the peritoneal cavity of nude mice. Avp53 administered intraperitoneally
      eradicated microscopic and small-sized tumor nodules, demonstrating that the
      intraperitoneal administration of Avp53 may serve as an effective adjuvant
      therapy for ovarian cancers.

PMID- 11576285
TI  - Difficulties using the Franco-Italian Glossary in assessing toxicity of cervical
      cancer treatment.
AB  - Shakespeare TP, Ferrier AJ, Holecek MJ, Jagavkar RS, Stevens MJ. Difficulties
      using the Franco-Italian Glossary in assessing toxicity of cervical cancer
      treatment. Int J Gynecol Cancer 1998; 8: 51-55 We assessed the toxicities of
      patients treated for cervical cancer using the revised Franco-Italian Glossary
      (FIG). A total of 69 separate complications were appraised in 47 patients;
      however, only 43.5% of these side-effects could be accurately graded. In all,
      56.5% of toxicities could not be scored for a variety of reasons: (1) the FIG
      does not account for all possible complications of cervical cancer treatment; (2)
      some important toxicities are regarded as too minor to be graded; (3) subjective
      assessment of some side-effects did not allow consensus to be reached when
      assigning a grade; (4) we could not accurately score toxicities using the FIG in
      a retrospective manner. Previous studies utilizing the FIG retrospectively have
      noted few problems with its use, with no indication of the number of toxicities
      unable to be graded. In view of the inability to grade the majority of
      complications in the present study in an accurate manner, we conclude that the
      revised FIG requires detailed data that are best collected prospectively and that
      several minor modifications of the glossary should be considered. Results of
      studies using the glossary retrospectively should be viewed with caution.

PMID- 11576286
TI  - Restricted surgical management of vulvar intraepithelial neoplasia 3: Focus on
      exclusion of invasion and on relief of symptoms.
AB  - van Beurden M, van der Vange N, ten Kate FJW, de Craen AJM, Schilthuis MS, Lammes
      FB. Restricted surgical management of vulvar intraepithelial neoplasia 3: Focus
      on exclusion of invasion and on relief of symptoms. Int J Gynecol Cancer 1998; 8:
      73-77. A study was undertaken to determine the effectiveness of extensive and
      restricted surgery for vulvar intraepithelial neoplasia (VIN) 3. All consecutive
      patients with VIN 3 admitted to a tertiary referral hospital were included. The
      main outcome measures were relief and recurrence of symptoms and progression to
      invasive disease in patients with VIN 3 after extensive or restricted surgery. Of
      every vulvoscopic visible lesion a biopsy was taken to establish extent and grade
      of VIN and to rule out invasive carcinoma. Patients with unifocal VIN 3 underwent
      extensive surgery. Patients with multifocal VIN 3 underwent extensive or
      restricted surgery or an expectant management was adopted, depending on the
      existence of symptoms and the presence of invasive vulvar carcinoma. Forty-seven
      patients were evaluated. Eighty-three percent of patients had a long history of
      symptoms. Eight patients (17%) had unifocal VIN 3. In 9% of the patients a
      superficially invasive vulvar carcinoma was found, ie with a depth of invasion of
      1 mm or less. Only 20% of the extensively operated patients had free surgical
      margins. There was recurrence of symptoms in all of the extensively operated
      patients, in contrast to a 26% persistence or recurrence rate of symptoms in the
      restrictedly operated patients. In patients with multifocal VIN 3 who underwent
      restricted surgery, young age of the patient (P = 0.02) and large extension of
      VIN 3 (P = 0.02) were significant factors in predicting persistence or recurrence
      of symptoms. Only once was a superficially invasive vulvar carcinoma diagnosed
      during follow-up, and this was in an extensively operated patient.
      Vulvoscopically directed biopsies in VIN 3 are a safe method to exclude invasive
      disease. Restricted surgery is effective in relieving symptoms in multifocal VIN
      3.

PMID- 11576287
TI  - Recurrent cervical carcinoma after radical hysterectomy: an analysis of clinical
      aspects and prognosis.
AB  - Samlal RAK, van der Velden J, van Eerden T, Schilthuis MS, Gonzalez Gonzalez D,
      Lammes FB. Recurrent cervical carcinoma after radical hysterectomy: an analysis
      of clinical aspects and prognosis. Int J Gynecol Cancer 1998; 8: 78-84. The
      purpose of the present study was to evaluate the clinical aspects and prognosis
      of patients with tumor recurrence in surgically treated stage IB and IIA cervical
      carcinoma patients. Two hundred and seventy-one stage IB and IIA cervical
      carcinoma patients underwent a Wertheim Okabayashi radical hysterectomy with
      pelvic lymphadenectomy. The median follow-up time was 60 months. Recurrence
      occurred in 27 patients (10%): 14 had a pelvic recurrence and 13, and extrapelvic
      recurrence. The site of recurrence was influenced by various pathological factors
      as well as by the primary treatment mode. 77% of recurrences were detected within
      three years after primary treatment. The median recurrence-free interval in
      patients with a pelvic recurrence was significantly shorter than in patients with
      an extrapelvic recurrence (14 months vs. 17 months, P = 0.03). The mortality rate
      of the group of patients with recurrent disease was 85% (23/27). Patients with a
      pelvic central recurrence had a significantly better outcome than did patients
      whose recurrences were located at the pelvic sidewall. Two patients with a
      pulmonary recurrence were treated with surgery and show no evidence of disease
      after 4 and 8 years respectively, of follow-up. The overall detection rate of
      recurrent disease by routine follow-up was only 36%. However, asymptomatic
      patients had a significantly better prognosis when compared with symptomatic
      patients. Therefore, we recommend frequent follow-up visits during the first 3
      years after primary treatment to detect recurrence in an early stage.

PMID- 11576288
TI  - The importance of using confidence intervals when reporting results of studies in
      abstract form.

PMID- 11576290
TI  - A history of influenza.

PMID- 11576291
TI  - Vaba, Haiza, Kholera, Foklune or Cholera: in any language still the disease of
      seven pandemics.

PMID- 11576292
TI  - The Great Pox that was...syphilis.

PMID- 11576293
TI  - The life and works of Louis Pasteur.

PMID- 11576294
TI  - Coccidioides immitis as a Select Agent of bioterrorism.

PMID- 11576295
TI  - Plague vaccine research and development.

PMID- 11576296
TI  - The development of new vaccines against Bacillus anthracis.

PMID- 11576297
TI  - Preliminary analysis and annotation of the partial genome sequence of Francisella
      tularensis strain Schu 4.

PMID- 11576298
TI  - Dangerous Pathogens 2000: an overview of the international conference.

PMID- 11576299
TI  - Succession of microbial communities during a biostimulation process as evaluated
      by DGGE and clone library analyses.
AB  - AIMS: The objective of this study was to investigate the changes in the
      indigenous bacterial community structure for assessing the impact of
      biostimulation on spilled oil. METHODS AND RESULTS: Changes in the bacterial
      community structure were monitored by denaturing gradient gel electrophoresis
      (DGGE) and clone library methods based on 16S rRNA gene (rDNA) sequences. The
      results of DGGE, coupled with the use of the Shannon index and principal
      component analysis (PCA) and clone library analyses, were consistent. In the
      treated (fertilized) area, one operational taxonomic unit (OTU) became dominant
      during the fertilization period, and it was most closely related to Pseudomonas
      putida. CONCLUSIONS: The bacterial community structure in the treated area was
      markedly different from that in the control (non-fertilized) area during the
      fertilization period, but in the two areas it became similar at 14 weeks after
      the end of fertilization. SIGNIFICANCE AND IMPACT OF THE STUDY: The results
      suggest that the bacterial community structure was disrupted by the
      biostimulation treatment, but that it recovered immediately after the end of
      fertilization.

PMID- 11576300
TI  - Purification and characterization of a bacteriocin-like compound (Lichenin)
      produced anaerobically by Bacillus licheniformis isolated from water buffalo.
AB  - AIMS: To characterize a bacteriocin-like factor from Bacillus licheniformis 26 L
      10/3RA isolated from buffalo rumen. METHODS AND RESULTS: The culture supernatant
      exhibited the antibacterial activity against a number of indicator organisms in a
      cut-well agar assay under anaerobic conditions. The inhibitory component was
      purified by following ammonium sulphate precipitation, gel filtration and ion
      exchange chromatography and confirmed to be a single peptide. A single band on
      tricine-sodium dodecyl sulphate-polyacrylamide gel electrophoresis confirmed that
      the peptide was purified to homogeneity and having an estimated molecular mass of
      approximately 1400 dalton. Complete amino acid sequence of the peptide yielded 12
      amino acids from the N-terminal end (ISLEICXIFHDN). No homology with previously
      reported bacteriocins was observed and has been designated as Lichenin. Lichenin
      was found to be hydrophobic, sensitive to atmospheric oxygen, retained biological
      activity even after boiling for 10 min and was active over a pH range of 4.0-9.0.
      CONCLUSIONS: The Lichenin represents the first anaerobiosis specific expression
      of bacteriocin-like compound isolated from Bacillus licheniformis 26 L-10/3RA of
      buffalo rumen origin. SIGNIFICANCE AND IMPACT OF THE STUDY: Lichenin could be a
      potential candidate for manipulating the rumen function at molecular level
      intended for improving the productivity of the ruminant.

PMID- 11576301
TI  - Biofilms and microbially influenced cuprosolvency in domestic copper plumbing
      systems.
AB  - AIMS: To survey biofilm accumulation within domestic copper plumbing pipes in
      South Australian drinking water distribution systems and examine its role in
      copper solvation (cuprosolvency). METHODS AND RESULTS: Cold water copper pipes
      were sampled from two different plumbing systems receiving filtered and
      unfiltered potable water respectively. Biomass was quantified by total organic
      carbon measurements and viable cell counts and microbial activity by
      respirometry. Biofilm accumulation was related to water chemistry within the
      systems, particularly nutrients, alkalinity and conductivity, as well as water
      turbulence. Laboratory coupon experiments were used to determine the effect of
      extracted biofilm on copper solvation. Biofilms were shown to be capable of both
      increasing and decreasing aqueous copper concentrations in comparison to sterile
      controls. CONCLUSIONS: The results suggest that water quality may influence the
      accumulation of biofilms in copper plumbing systems, as well as potential
      cuprosolvency activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of
      biofilms in copper plumbing systems and their ability to influence aqueous copper
      concentrations has implications for both public health and the management of
      distribution systems.

PMID- 11576302
TI  - Mode of antagonism of Brevibacillus brevis against Botrytis cinerea in vitro.
AB  - AIMS: To assess the activity of Brevibacillus brevis (formerly Bacillus brevis)
      Nagano and the antibiotic it produces, gramicidin S, against the plant pathogen
      Botrytis cinerea. METHODS AND RESULTS: Germination and growth of Bot. cinerea
      were assessed in the presence of B. brevis or gramicidin S in liquid media, on
      solid media and on leaf sections of Chinese cabbage. Germination was 10-fold more
      sensitive to gramicidin S than growth. Inhibition of Bot. cinerea was greater in
      liquid media compared with on solid media. Activity of gramicidin S against Bot.
      cinerea on leaf sections was much lower than in vitro. In vitro inhibition of
      Bot. cinerea by B. brevis Nagano was similar to equivalent levels of gramicidin.
      CONCLUSIONS: Antibiosis, via gramicidin S, is the mode of antagonism exhibited by
      B. brevis Nagano against Bot. cinerea in vitro. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The mode of antagonism of B. brevis against Bot. cinerea was elucidated.
      The differing activity of gramicidin S against Bot. Cinerea in vitro and on leaf
      sections indicates one mechanism by which biocontrol activity may differ between
      laboratory and field conditions.

PMID- 11576303
TI  - The use of Lenticules for the process control of enumeration techniques in food
      and environmental microbiology.
AB  - AIMS: Lenticules consist of control-dried plano convex discs in which
      biologically-active materials are contained within a water-soluble matrix. They
      can be produced to contain stable numbers of bacteria from 10 cfu lenticule-1 to
      108 cfu lenticule-1 with a wide variety of organisms. These experiments were
      carried out to validate their use as a tool for internal quality control in
      quantitative microbiology. METHODS AND RESULTS: The Lenticules were used
      routinely in standard quantitative microbiological procedures across five
      laboratories. Results showed the materials to be stable, homogeneous and capable
      of identifying systematic errors. CONCLUSIONS: The Lenticules provide suitable,
      stable control materials. SIGNIFICANCE AND IMPACT OF THE STUDY: Routine internal
      quality control of quantitative measurements is greatly improved; the materials
      are easy to use and enable comparisons between laboratories to be made.

PMID- 11576304
TI  - Microcosm enrichment of 1,3-dichloropropene-degrading soil microbial communities
      in a compost-amended soil.
AB  - AIMS: A microcosm-enrichment approach was used to investigate bacterial
      populations that may represent 1,3-dichloropropene (1,3-D)-degrading micro
      organisms in compost-amended soil. METHODS AND RESULTS: After 8 weeks of
      incubation, with repeated application of 1,3-D, volatilization fluxes were much
      lower for compost-amended soil (CM) than with the unamended soils, indicating
      accelerated degradation due to addition of compost, or development of new
      microbial populations with enhanced degradation capacity. Denaturing gradient gel
      electrophoresis (DGGE) profiles of the PCR-amplified region of 16S rDNA genes
      were used to identify dominant bacterial populations in the fumigant-degrading
      soil. The DGGE results indicated that specific bacterial types had been enriched,
      and a more diverse fingerprint was observed in the community derived from the
      compost-amended soil compared with the unamended soil. Fragments from 16
      different DGGE bands were cloned, sequenced and compared with published 16S rDNA
      sequences. Two clones, designated E1 and E4, were unique to all soils to which
      compost was added, and corresponded to strains of Pseudomonas and Actinomadura,
      respectively. CONCLUSIONS: The results show that the addition of compost to soil
      increases specific microbial populations and results in the accelerated
      degradation of fumigants. SIGNIFICANCE AND IMPACT OF THE STUDY: Application of
      compost manure to soil can help degrade soil fumigants at a faster rate.

PMID- 11576305
TI  - Subcellular distribution of glycanases and related components in Ruminococcus
      albus SY3 and their role in cell adhesion to cellulose.
AB  - AIMS: To compare the subcellular distribution of glycanase-related components
      between wild-type Ruminococcus albus SY3 and an adhesion-defective mutant, to
      identify their possible contribution to the adhesion process, and to determine
      their association with cellulosome-like complexes. METHODS AND RESULTS: Cell
      fractionation revealed that most of the cellulases and xylanases were associated
      with capsular and cell-wall fractions. SDS-PAGE and gel filtration indicated that
      most of the bacterial enzyme activity was not integrated into cellulosome-like
      complexes. The adhesion-defective mutant produced significantly less (5- to 10
      fold) overall glycanase activity, and the 'true cellulase activity' appeared to
      be entirely confined to the cell membrane fractions. Antibodies specific for the
      cellulosomal scaffoldin of Clostridium thermocellum recognized a single 240 kDa
      band in R. albus SY3. CONCLUSIONS: The adhesion-defective mutant appeared to be
      blocked in exocellular transport of enzymes involved in true cellulase activity.
      A potential cellulosomal scaffoldin candidate was identified in R. albus SY3.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Several glycanase-related proteins and more
      than one mechanism appear to be involved in the adhesion of R. albus SY3 to
      cellulose.

PMID- 11576306
TI  - Use of ribotyping and random amplified polymorphic DNA to differentiate isolates
      of Burkholderia andropogonis.
AB  - AIMS: The aim of this study was to determine the genetic diversity among isolates
      of Burkholderia andropogonis from various host plant species and geographic
      locations. METHODS AND RESULTS: Both random amplified polymorphic DNA (RAPD) and
      ribotyping analyses were used to assess the diversity of B. andropogonis isolates
      and compare these results with pathogenicity assays carried out on a number of
      common hosts of the organism. CONCLUSIONS: Both RAPD and ribotyping analyses
      revealed a high level of genetic diversity between isolates of B. andropogonis.
      Both methods demonstrated a similar clustering of isolates. However, there was no
      strict correlation between the genetic diversity revealed and the original host,
      geographic location or pathogenicity of the isolates. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This is the first report on the genetic diversity of isolates of B.
      andropogonis. The great degree of diversity revealed in this study contrasts with
      the lack of phenotypic diversity within this species.

PMID- 11576307
TI  - Heat inactivation data for Mycobacterium avium subsp. paratuberculosis:
      implications for interpretation.
AB  - AIMS: We discuss several factors that are critical for heat inactivation
      experiments and which should be taken into account for future research. METHODS
      AND RESULTS: On the basis of examples from the literature we discuss critical
      factors influencing the calculated heat inactivation of Mycobacterium avium
      subsp. paratuberculosis (MAP). Furthermore, using a modelling approach, we show
      that tailing of the inactivation curve of MAP is caused by the presence of cell
      clumps and not by a more heat-resistant cell fraction. CONCLUSIONS: The
      experimental conditions of the MAP heat inactivation studies of different
      research groups vary significantly and lead to considerable differences in
      results and conclusions. Therefore, a more consensual approach should be employed
      in future studies. In addition, our model on clumping of MAP can be used to
      predict the decimal reduction of MAP during heat treatment and to study the
      effect of clumping on other lethal effects. SIGNIFICANCE AND IMPACT OF THE STUDY:
      We discuss several factors that should be carefully considered in heat resistance
      experiments. This is essential for a thorough interpretation of results from
      experiments and should be given proper attention in future experiments and
      publications on this topic.

PMID- 11576308
TI  - pH-controlled cell release and biomass distribution of alginate-immobilized
      Lactococcus lactis subsp. lactis.
AB  - AIMS: To investigate the growth and release of Lactococcus lactis subsp. lactis
      in gel beads and to affect rates of cell release by changing the growth
      conditions. METHODS AND RESULTS: The rate of release and the distribution of
      immobilized L. lactis subsp. lactis in alginate beads were studied in continuous
      fermentations for 48 h. A change in operating pH from 6.5 to 9.25 initially
      reduced the ratio of the rates of cell release to lactate production by almost a
      factor of 105. Compared with fermentations at pH 6.5, growth at pH 9.25 also
      increased the final internal bead biomass concentration by a factor of 5 and
      increased the final rate of lactate production by 25%. After 48 h, the ratio of
      the rates of cell release to lactate production was still 10 times lower than in
      fermentations at pH 6.5. CONCLUSIONS: A change in the operating pH from 6.5 to
      9.25 reduced rates of cell release throughout 48 h of fermentation and increased
      the final rates of lactate production and internal bead biomass concentration.
      SIGNIFICANCE AND IMPACT OF THE STUDY: These data illustrate that diffusional
      limitations and corresponding pH gradients can be exploited in affecting the
      distribution of immobilized growing cells and their concomitant release.

PMID- 11576309
TI  - Temperature shock, injury and transient sensitivity to nisin in Gram negatives.
AB  - AIMS: The effect of thermal stresses on survival, injury and nisin sensitivity
      was investigated in Salmonella Enteritidis PT4, PT7 and Pseudomonas aeruginosa.
      METHODS AND RESULTS: Heating at 55 degrees C, rapid chilling to 0.5 degrees C or
      freezing at -20 degrees C produced transient sensitivity to nisin. Cells were
      only sensitive if nisin was present during stress. Resistance recovered rapidly
      afterwards, though some cells displayed residual injury. Injury was assessed by
      SDS sensitivity, hydrophobicity changes, lipopolysaccharide release and NPN
      uptake. LPS release and hydrophobicity were not always associated with transient
      nisin sensitivity. Uptake of NPN correlated better but persisted longer after
      treatment. CONCLUSIONS: Thermal shocks produce transient injury to the outer
      membrane, allowing nisin access. After treatment, the permeability barrier is
      rapidly restored by a process apparently involving reorganization rather than
      biosynthetic repair. SIGNIFICANCE AND IMPACT OF THE STUDY: Inclusion of nisin
      during food treatments that impose sub-lethal stress on Gram negatives could
      increase process lethality, enhancing microbiological safety and stability.

PMID- 11576310
TI  - Adsorption, attachment and biofilm formation among isolates of Listeria
      monocytogenes using model conditions.
AB  - AIMS: To determine whether isolates of Listeria monocytogenes differ in their
      ability to adsorb and form biofilms on a food-grade stainless steel surface.
      METHODS AND RESULTS: Strains were assessed for their ability to adsorb to a test
      surface over a short time period. Although some differences in numbers of bound
      cells were found among the strains, there were no correlations between the degree
      of adsorption and either the serotype or source of the strain. The ability of
      each strain to form a biofilm when grown with the test surface was also assessed.
      With the exception of a single strain, all strains adhered as single cells and
      did not form biofilms. Significant differences in adherence levels were found
      among strains. Strains demonstrating enhanced attachment produced extracellular
      fibrils, whereas those which adhered poorly did not. A single strain formed a
      biofilm consisting of adhered single cells and aggregates of cells. CONCLUSIONS:
      Significant differences were found in the ability of various L. monocytogenes
      strains to attach to a test surface. In monoculture, the majority of strains did
      not form biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: Differences in
      attachment and biofilm formation among strains provide a basis to study these
      characteristics in L. monocytogenes.

PMID- 11576311
TI  - Challenge testing of the lactoperoxidase system in pasteurized milk.
AB  - AIMS: To determine the role of lactoperoxidase (LP) in inhibiting the growth of
      micro-organisms in pasteurised milk. METHODS AND RESULTS: Four micro-organisms of
      importance in the spoilage of pasteurized milk were challenged in lactoperoxidase
      (LP)-enriched ultra-heat treated (UHT) milk after subsequent pasteurization. Milk
      samples were stored at the optimum temperatures for growth of the individual
      bacteria. Pasteurization was carried out at 72 degrees C/15 s and 80 degrees C/15
      s to determine the effect of the LP system on the micro-organisms. An active LP
      system was found to greatly increase the keeping quality (KQ) of milks inoculated
      with Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus thermophilus
      and pasteurized at 72 degrees C, but had little or no effect in milks heated at
      80 degrees C, presumably due to virtual inactivation of LP at 80 degrees C.
      However, pasteurization temperature had no effect on the KQ of milks challenged
      with Bacillus cereus spores. CONCLUSIONS: This study suggests that the LP system,
      rather than heat-shocking of spores, is responsible for the greater KQ of milk
      pasteurized at 72 degrees C/15 s compared with 80 degrees C/15 s. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The study emphasizes the care required in selecting
      pasteurization temperatures in commercial practice and to avoid the temptation to
      compensate for inferior quality of raw milk by increasing pasteurization
      temperature.

PMID- 11576312
TI  - Diversity of pseudomonads isolated from three different plant rhizospheres.
AB  - AIMS: To study the diversity of the Pseudomonas populations isolated from three
      different plant rhizospheres, namely pearl millet, cotton and paddy, grown in
      saline soils along the coastline of Southern India. METHODS AND RESULTS: The
      Pseudomonas populations were analysed for their biochemical characters and
      genetic diversity using molecular tools including RAPD and PCR-RFLP. The
      biochemical characterization, antibiotic resistance assay and RAPD profiles
      revealed a largely homogeneous population. Even in PCR-RFLP restriction studies,
      only two groups of isolates were seen. One group was predominant in all three
      rhizospheres, while the other minor group consisted of salt-sensitive isolates
      restricted to the paddy rhizosphere alone. CONCLUSIONS: It was observed that
      increasing salinity caused a predominant selection of salt-tolerant species, in
      particular Ps. pseudoalcaligenes and Ps. alcaligenes, irrespective of the host
      rhizosphere. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has reinstated the
      importance of the soil over the host plant with regard to rhizosphere
      populations. It has also resulted in the isolation of several salt-tolerant
      Pseudomonas strains, which are being screened for their biological control
      activity against common plant pathogens of the coastal agri-ecosystem.

PMID- 11576313
TI  - Persistence of Escherichia coli, Salmonella choleraesuis, Aujeszky's Disease
      virus and Blue Eye Disease virus in ensilages based on the solid fraction of pig
      faeces.
AB  - AIMS: This study was carried out to determine the survival time of Escherichia
      coli, Salmonella choleraesuis, Aujeszky's Disease virus and Blue Eye Disease
      virus in ensilages based on the solid fraction of pig faeces. METHODS AND
      RESULTS: The four micro-organisms were inoculated into microsilos based on the
      solid fraction of pig faeces, sorghum and molasses. They were left for 0, 7, 14,
      28 and 56 days, after which the state of each microsilo was evaluated, and
      isolation of the inoculated agents was attempted. The four inoculated agents were
      isolated only on day 0 of ensilage. The viral agents were identified through the
      cytopathic effect and fluorescence. CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE
      STUDY: It is concluded that ensilages based on the solid fraction of pig faeces
      appear to reduce the risk of the transmission of the agents inoculated in this
      study and help to reduce the environmental impact by using the solid in animal
      feed.

PMID- 11576314
TI  - Drug safety--important to us all!

PMID- 11576315
TI  - Developing an optimal approach to global drug safety.
AB  - An increasing number of media reports on a number of marketed drugs withdrawn
      because of harmful effects, a scientific report on epidemic proportions of
      serious adverse drug reactions in hospitalized patients, and a disturbing report
      on medical mistakes that includes medication errors have recently all brought
      drug safety into intense focus and placed it under greater scrutiny. Concerted
      efforts are now being made to understand the causes of drug safety problems and
      to find ways to reduce their frequency. An international symposium, 'Developing
      an Optimal Approach to Drug Safety' was held at Wake Forest University in the
      Fall of 2000 to identify the issues and solutions to extant problems in this
      area. This report summarizes the resulting discussions of global postmarketing
      surveillance initiatives and describes efforts to reduce medication errors, and
      improve global communication about drug safety.

PMID- 11576316
TI  - Fruit and vegetable consumption in the prevention of cancer: an update.
AB  - Fruit and vegetables are considered to be important means of preventing cancer
      through diet. However, several recent large prospective cohort studies and
      clinical trials have found no associations regarding several major cancers,
      including cancers of the colon, breast and stomach. Although these results are
      disconcerting, especially for health-conscious individuals, there is also
      mounting evidence that people who avoid fruit and vegetables completely, or
      consume very little, are indeed at increased risk of these cancers. These
      individuals in particular should be identified, with the goal of helping them
      find ways to include more fruit and vegetables in their diets.

PMID- 11576317
TI  - Factors influencing the relation between alcohol and mortality--with focus on
      wine.
AB  - The impact of alcohol intake on mortality has been described in a large number of
      prospective population studies from many countries. Most have shown a J-shaped
      relation between alcohol intake and subsequent mortality, indicating that there
      are both beneficial and harmful effects of ethanol on health. In exploring the
      French paradox, it has been suggested that wine may have beneficial effects
      additional to that of ethanol. Recently, several prospective population studies
      have supported this idea. However, it is also likely that the apparent additional
      beneficial effect of wine on health is confounding.

PMID- 11576318
TI  - Idiopathic environmental intolerances (formerly multiple chemical sensitivity)
      psychiatric perspectives.
AB  - Idiopathic environmental intolerances (IEI)/multiple chemical sensitivity (MCS)
      is characterized by various somatic symptoms which cannot be explained
      organically, but are attributed to the influences of toxic environmental
      chemicals in low, usually harmless doses. In the absence of a widely accepted
      definition of IEI, contradictory aetiological hypotheses and therapeutic
      suggestions are discussed. Some authors doubt the existence of IEI/MCS as a
      disease entity of its own. The label IEI does not implicate neither a diagnosis
      of somatic disease nor that it is caused by an avoidable exposure. Many IEI
      patients suffer from psychiatric diseases. A majority of them can be diagnosed as
      somatoform disorders. Consequently, psychiatric therapies could be effective.
      This review describes the current knowledge about IEI/MCS, outlines a diagnostic
      algorithm and a psychotherapeutic concept for variants of IEI understood as a
      somatoform disorder.

PMID- 11576320
TI  - Fatal adverse drug events: the paradox of drug treatment.
AB  - OBJECTIVE: Study patient characteristics, morbidity patterns and drug regimens
      associated with fatal adverse drug events (FADEs) amongst medical department
      inpatients. DESIGN: An observational, descriptive study using aggregated medical
      records, autopsies and pre and postmortem drug analyses. SETTING: A department of
      internal medicine at a Norwegian county hospital. SUBJECTS: All patients dying in
      the department over a 2-year period. RESULTS: The incidence of FADEs were 18.2%
      (133/732). Compared with non-FADE cases, FADE cases were older, used more drugs
      both on admission and at death, and had higher comorbidity (P < 0.001). Drugs
      suspected to cause or contribute to fatal outcome were mainly those used for
      treating chronic pulmonary diseases (terbutaline, theophylline), antithrombotic
      drugs (aspirin, warfarin, heparines) and drugs for treating coronary heart
      disease and heart failure (e.g. diuretics, nitrates, angiotensin converting
      enzymes (ACE) inhibitors, calcium channel blockers). Bronchodilatory drugs,
      antithrombotic drugs and cardiovascular drugs account for 26, 31 and 30 FADE
      cases, respectively. Patients dying from gastrointestinal diseases had the
      highest relative FADE occurrence (42%), cancer patients the lowest occurrence
      (4%). Serious drug-drug and drug-disease interactions were frequently suspected.
      Various degrees of inappropriateness in choice of drug, dosage or administration
      route were seen in 50% of FADE cases. CONCLUSIONS: This study shows a high
      incidence of FADEs associated with high age, high comorbidity and polypharmacy,
      and partly to inappropriate drug prescribing or use. Treatments frequently
      associated with FADEs were bronchodilatory treatment of patients with both
      chronic obstructive lung disease and coronary heart disease, vasodilatory
      treatment in patient with endstage heart failure and the combination of several
      antithrombotic drugs. A systematic strategy is needed to avoid unnecessary
      adverse drug events (ADEs).

PMID- 11576319
TI  - Effective blood pressure treatment improves LDL-cholesterol susceptibility to
      oxidation in patients with essential hypertension.
AB  - OBJECTIVES: LDL-cholesterol particles from hypertensive patients exhibit enhanced
      susceptibility to in vitro oxidation, an abnormality thought to increase
      cardiovascular risk. We tested whether blood pressure (BP) normalization can
      reverse this abnormality. DESIGN: Double-blind, randomized pharmacological
      intervention trial. SETTING: Clinical research centre. Subjects. A total of 29
      nondiabetic, normolipidaemic patients with essential hypertension (BP= 151 +/-
      3/99 +/- 1 mmHg) and 11 normotensive controls (BP=125 +/- 3/85 +/- 1 mmHg)
      matched for gender, age, obesity, glucose tolerance and lipid profile.
      Intervention. Anti-hypertensive treatment for 3 months with a calcium-antagonist
      in randomized combination with either an ACE inhibitor or a beta-blocker. MAIN
      OUTCOME MEASURES: Lag phase of copper-induced LDL oxidation, cell-mediated (human
      umbilical vein endothelium) generation of malondialdehyde (MDA) by LDL and
      vitamin E content in LDL. RESULTS: At baseline in hypertensives versus controls,
      lag phase was shorter (89 +/- 3 vs. 107 +/- 6 min, P < 0.04), MDA generation was
      higher (5.8 +/- 0.1 vs. 5.1 +/- 0.2 nmol L(-1), P=0.002), and vitamin E was
      reduced (6.40 +/- 0.05 vs. 6.67 +/- 0.11 microg mg(-1), P=0.03). At 3 months, BP
      was normalized (124 +/- 3/81 +/- 1, P < 0.0001 vs. baseline, P=ns versus
      controls), lag phase was prolonged (to 98 +/- 3 min, P=0.0005), MDA generation
      was reduced (5.6 +/- 0.1 nmol L-1, P = 0.001), and vitamin E was increased (6.53
      +/- 0.05 microg mg(-1), P=0.003), with no significant differences between the
      randomized groups. CONCLUSIONS: In nondiabetic, nonobese, normolipidaemic
      patients with essential hypertension, LDL susceptibility to copper- and cell
      mediated oxidation is increased. BP normalization is associated with a
      significant improvement, but not a full reversal, of this abnormality.

PMID- 11576321
TI  - Chronic mild neutropenia in adults: relation to IgG3 deficiency and infection
      susceptibility.
AB  - OBJECTIVES: Chronic mild neutropenias (NP, i.e. absolute neutrophil blood
      counts/ANC/0.5-1.5 x 10(9) L(-1)) are accompanied by a variable infection
      susceptibility, which may or may not be as a result of concomitant conditions.
      Here, we assessed whether such patients also displayed an immunoglobulin
      deficiency and if this condition contributed to infection proneness. DESIGN,
      SETTING AND SUBJECTS: Thirty consecutive adult Caucasian patients with chronic
      mild NP were followed at one university hospital for up to 28 years. Comparisons
      were made with 49 IgG3 deficiency patients at an immunodeficiency clinic. MAIN
      OUTCOME MEASURES: Recorded infections, ANC and serum immunoglobulin levels; flow
      cytometry assessments of blood lymphocyte subsets and tests for autoimmunity were
      run to determine neutropenia subtypes. RESULTS: Forty per cent of the NP patients
      were treated for severe or recurrent infections. The mean IgG3 value for the NP
      patients was significantly lower than for healthy controls (P < 0.005) and 33% of
      the patients displayed IgG3 values below the reference values (i.e. below 0.21 g
      L(-1)), and an additional 13% had IgG3 values within the range others consider
      low (0.21-0.41 g L(-1)). Unexpectedly, neutropenic IgG3 deficiency patients
      exhibited less infection proneness than those with normal IgG3 values (P=0.03).
      Patients with autoimmune, large granular lymphocyte-associated or idiopathic NP
      had IgG3 deficiency in 63, 44 and 38%, respectively. In addition, none of IgG3
      deficiency patients followed at the immunodeficiency clinic displayed
      neutropenia. CONCLUSION: IgG3 deficiency is common amongst chronic mild
      neutropenia patients, particularly in those with autoimmune background, but
      contributes not significantly to infection susceptibility.

PMID- 11576322
TI  - Gender specific associations of the Trp64Arg mutation in the beta3-adrenergic
      receptor gene with obesity-related phenotypes in a Mediterranean population:
      interaction with a common lipoprotein lipase gene variation.
AB  - OBJECTIVE: To investigate the association between the Trp64Arg beta3-adrenergic
      receptor (ADRB3) mutation and obesity-related phenotypes in a Mediterranean
      Spanish population considering the effect of other genetic and environmental
      factors. DESIGN AND SUBJECT: Cross-sectional study in 1063 (476 men and 587
      women) randomly selected from this population (aged: 18-68 years). MEASUREMENTS:
      Anthropometric (weight, height and waist-to-hip ratio), blood pressure,
      biochemical (lipids, fasting glucose, and uric acid), life-style variables, and
      the Trp64Arg, HindIII-Lipoprotein lipase (LPL) and apolipoprotein E polymorphism.
      RESULTS: Frequency of the Arg64 allele was low (0.051; 95% CI: 0.042-0.060). We
      found gender-specific associations between the Trp64Arg mutation and obesity
      related phenotypes. In men, carriers of the Arg64 variant had higher body mass
      index (BMI) (27.63 +/- 3.81 vs. 26.34 +/- 3.57 kg m-2, P=0.049) and total
      cholesterol (5.85 +/- 1.45 vs. 5.28 +/- 1.06 mmol L-1; P=0.011) compared with
      wild-type individuals. Logistic regression analysis, revealed that the risk of
      overweight was two times higher in male carriers of the Arg64 allele. In women,
      the Arg64 variant was only associated with higher fasting glucose (P=0.031).
      These genotype effects persisted after adjustment for age, genetic and life-style
      variables. For the LPL polymorphism, the H-/H- genotype was associated with lower
      BMI and with lower risk of overweight (OR: 0.49; 95% CI: 0.30-0.81) in both men
      and women. However, after adjustment for covariates, these associations only
      remained statistically significant (P < 0.02) in women. Moreover, in women, a
      statistically significant interaction (P=0.026) between the LPL and the ADRB3
      gene loci in determining BMI was found. Thus, the Arg64 allele was associated
      with a higher BMI only in H+/H+ women. CONCLUSIONS: The Trp64Arg mutation was
      associated with BMI and lipids in men. In women, an additional gene-gene
      interaction with the LPL-HindIII polymorphism may explain the results.

PMID- 11576323
TI  - Prevalence of undiagnosed coeliac syndrome in osteoporotic women.
AB  - OBJECTIVES: The aims of the study were to quantify the prevalence of asymptomatic
      coeliac disease (CD) in a cohort of osteoporotic females, and to investigate the
      features of bone loss. DESIGN AND SUBJECTS: We studied 255 women (mean age 66.6
      +/- 8.5 SD) with primary osteoporosis (WHO diagnostic criteria). After the first
      CD screening with the measure of serum IgG antigliadin antibodies (IgG-AGA), 53
      women showed a positive test: antibodies to tissue transglutaminase (TG-ab) were
      subsequently determined to confirm the diagnosis of CD. Bone metabolism was
      evaluated by: serum and urinary calcium, serum and urinary phosphate, serum
      alkaline phosphatase, urinary crosslaps, serum 25(OH)D and serum parathyroid
      hormone. RESULTS: High levels of IgG-AGA and TG-ab were observed in 24 patients
      with a prevalence of serological disease of 9.4%. These women were characterized,
      in comparison with the other patients, by a statistically significant reduction
      in serum 25(OH)D (17.8 +/- 7.2 vs. 55.1 +/- 20.3 nmol L(-1), P < 0.01) together
      with a significant increase of iPTH (65.1 +/- 29.7 vs. 35.1 +/- 20.0 pg mL(-1); P
      < 0.01). Patients with high TG-ab levels showed also slightly raised values of
      urinary crosslaps (288 +/- 88 vs. 270 +/- 90 microm mol(-1) Cr). In IgG-AG
      positive patients a statistically significant inverse correlation was found
      between 25(OH)D serum levels and log-transformed TG-ab values (r: -0.95, P <
      0.001). Intestinal biopsies were obtained in 10 TG-ab positive women and verified
      CD in six patients. CONCLUSIONS: These data support the hypothesis that patients
      with undiagnosed celiac disease develop high remodelling processes related to
      calcium malabsorption, secondary hyperparathyroidism and unavailability of
      vitamin D with a consequent more marked bone loss.

PMID- 11576324
TI  - Vincent duVigneaud 1901-1978: a personal tribute.

PMID- 11576325
TI  - Solution structures of the cytoplasmic linkers between segments S4 and S5 (S4-S5)
      in domains III and IV of human brain sodium channels in SDS micelles.
AB  - The two cytoplasmic linkers connecting segment S4 and segment S5 (S4-S5 linker)
      of both domain III (III/S4-S5) and IV (IV/S4-S5) of the sodium channel alpha
      subunit are considered to work as a hydrophobic receptor for the inactivation
      particle because of the three hydrophobic amino acids of Ile-Phe-Met (IFM motif)
      in the III-IV linker of the sodium channel alpha-subunit. To date, the solution
      structures of the peptides related to III/S4-S5 (MP-D3: A1325-M1338) and IV/S4-S5
      (MP-D4: T1648-L1666) of human brain sodium channels have been investigated using
      CD and (1)H NMR spectroscopies. SDS micelles were employed as a solvent. The
      micelles mimic either biological membranes or the interior of a protein and can
      be a relevant environment at the inactivated state of the channels. It was found
      that the secondary structures of both MP-D3 and MP-D4 assume alpha-helical
      conformations around the N-terminal half-side of the sequences, i.e. the residues
      between V1326 and L1331 in MP-D3 and between L1650 and S1656 in MP-D4. Residue
      A1329 in MP-D3, which is considered to interact with F1489 of the IFM motif, was
      found to be located within the alpha-helix. Residues F1651, M1654, M1655, L1657
      and A1669 in MP-D4, which also play an important role in inactivation, formed a
      hydrophobic cluster on one side of the helix. This cluster was concluded to
      interact with the hydrophobic cluster due to the III-IV linker before the
      inactivation gate closes.

PMID- 11576326
TI  - Structural and biosensor analyses of a synthetic biotinylated peptide probe for
      the isolation of adenomatous polyposis coli tumor suppressor protein complexes.
AB  - Large numbers of colon tumors stem from mutations in the gene coding for the
      production of the adenomatous polyposis coli (APC) tumor suppressor protein. This
      protein contains a coiled-coil N-terminal domain that is known to be responsible
      for homodimerization. Previous work by others has led to the design of a specific
      54-residue anti-APC peptide (anti-APCp1) that dimerizes preferentially with this
      domain. We have undertaken the chemical synthesis of a modified form of this
      peptide (anti-APCp2) that bears a biotin moiety at its N-terminus for use in
      subsequent ligand-binding analysis studies. The peptide was subjected to
      comprehensive chemical characterization to confirm its purity. Secondary
      structural analysis by circular dichroism spectroscopy and Fourier transform
      infrared spectroscopy indicated that the peptide could assume a wide range of
      potential conformations, depending upon the precise microenvironment.
      Significantly, a stable alpha-helical structure was generated when the solvent
      conditions supported intramolecular salt-bridge formation along the helix barrel.
      The biotinylated anti-APCp2 was immobilized onto a streptavidin sensor surface,
      in a specific orientation leaving all amino acids available to form a coiled
      structure. In one experiment, injection of colonic cell lysate extracts (LIM1215)
      onto a size-exclusion column resulted in the isolation of a high molecular mass
      protein peak (> 600 kDa) that reacted specifically with the immobilized anti
      APCp2 on the biosensor surface. In another experiment, a high molecular mass
      protein (M(r) > 250 kDa on SDS-PAGE) could be specifically immunoprecipitated
      from this peak using either the anti-APCp2 peptide or an anti-APC polyclonal
      antibody. This demonstrates the specific interaction between the anti-APCp2
      peptide and native APC and highlights the potential use of the former peptide in
      a multidimensional micropreparative chromatographic/biosensor/proteomic protocol
      for the purification of APC alone and APC complexed with different biopolymers in
      various cell lines, and stages of tumor development.

PMID- 11576327
TI  - Effects of temporins on molecular dynamics and membrane permeabilization in lipid
      vesicles.
AB  - Temporins are a novel family of small (10-13 residues) cationic antimicrobial
      peptides recently isolated from the skin of the European red frog Rana
      temporaria. Although recently acquired evidence shows that temporins have the
      potential to kill bacteria by permeabilizing the cytoplasmic membrane, the
      molecular mechanisms of membrane selectivity and permeabilization are largely
      unknown. In this study, it was found that temporins cause the release of
      fluorescent markers entrapped in phosphatidylcholine liposomes in a manner that
      depends significantly on the size of the solute. Temporins were also shown to
      lack a detergent-like effect on lipid vesicles, indicating that marker leakage
      caused by these peptides is not due to total membrane disruption but to
      perturbation of bilayer organization on a local scale. Binding of temporins to
      liposomes did lead to a small increase in lipid hydrocarbon chain mobility, as
      revealed by EPR spectroscopy of nitroxide-labeled fatty acids incorporated in the
      bilayer. Reference experiments were conducted using the bee venom peptide
      melittin, whose properties and behavior in natural and model membrane systems are
      well known. Our findings for temporins are discussed in relation to the models
      proposed to date to account for the action of antimicrobial peptides on
      membranes.

PMID- 11576328
TI  - Immunological evaluation of Escherichia coli-derived hepatitis C virus second
      envelope protein (E2) variants.
AB  - Two variants of the hepatitis C virus (HCV) E2 envelope protein, lacking the C
      terminal domain and comprising amino acids 458-650 (E2A) and 382-605 (E2C),
      respectively, were efficiently produced in BL21 (DE3) Escherichia coli cells. E2A
      and E2C were used to immunize mice. The E2C variant induced the maximal mean
      antibody titer. Anti-E2C mouse sera reacted mainly with E2 synthetic peptides
      covering the 70 amino acid N-terminal region of the E2 protein. Moreover, a panel
      of anti-HCV positive human sera recognized only the E2C protein (28.2%) and the
      synthetic peptide covering the HVR-1 of the E2 protein (23.1%). These data
      indicate the existence of an immunologically relevant region in the HVR-1 of the
      HCV E2 protein.

PMID- 11576329
TI  - 11-Demethylcyclosporins exhibit a single conformation in methanol and
      dimethylsulfoxide.
AB  - NMR studies showed that 11-demethylcyclosporin A (cyclosporin E) and 11
      demethylcyclosporin B exist as single species both in polar and nonpolar
      solvents. They adopt the same conformation that was found in the solid state.

PMID- 11576330
TI  - The nature of the bond between peptide and carrier molecule determines the
      immunogenicity of the construct.
AB  - The influence of the nature of the bond between a peptide and a (lipidic) carrier
      molecule on the immunogenicity of that construct was investigated. As types of
      bonds a thioester-, a disulfide-, an amide- and a thioether bond were
      investigated. As carrier molecules a peptide, an N-palmitoylated peptide or a
      C(16)-hydrocarbon chain were used. The biostability of the bond between peptide
      and carrier molecule is thioether > amide > disulfide >> thioester. However, the
      immunogenic potency of the constructs used was found to be thioester > disulfide
      > amide > thioether. In conclusion, a construct with a bond between peptide and
      (lipidic) carrier molecule that is more susceptible to biological degradation is
      more immunogenic when used in a peptide-based vaccine than a bond that is less
      susceptible to biological degradation.

PMID- 11576331
TI  - Development of a synthetic cyclized peptide derived from alpha-fetoprotein that
      prevents the growth of human breast cancer.
AB  - The peptide, EMTPVNPG, derived from alpha-fetoprotein, inhibits estrogen
      stimulated growth of immature mouse uterus and estrogen-dependent proliferation
      of human breast cancer cells. However, the biological activities of the peptide
      diminish over time in storage, even when in the lyophilized state, probably
      because of peptide aggregation through hydrophobic interaction among monomers.
      Two analogs of EMTPVNPG were designed with the intent of minimizing aggregation
      and retaining biological activity during prolonged storage. EMTOVNOG, where O is
      4-hydroxyproline, is a linear peptide generated by substituting 4-hydroxyproline
      for the two prolines, thereby increasing peptide hydrophilicity. This analog
      exhibited a dose-dependent inhibition of estrogen-stimulated growth of immature
      mouse uterus similar to that of EMTPVNPG (maximal activity at 1 microg/mouse). A
      second analog, cyclo-(EMTOVNOGQ), a hydrophilic, cyclic analog with increased
      conformational constraint, was as potent as the other peptides in its inhibition
      of estrogen-dependent growth of immature mouse uterus, and had an expanded
      effective dose range. Both linear and cyclized hydroxyproline-substituted analogs
      exhibited indefinite shelf-life. Furthermore, both analogs inhibited the estrogen
      dependent growth of MCF-7 human breast cancer growing as a xenograft in SCID
      mice. These analogs may become significant, novel agents for the treatment of
      breast cancer.

PMID- 11576332
TI  - A hydrophilic residue at position 2 can improve specific biological responses in
      fMLP-OMe analogs.
AB  - The peptides for-Met-Ser-Phe-OMe 1, for-Met-Cys-Phe-OMe 2, for-Met-Lys-Phe-OMe 3,
      and for-Met-Tyr-Phe-OMe 4 were synthesized in order to investigate the importance
      of a hydrophilic side-chain on the residue at position 2 on biological activities
      of human neutrophils. Our results seem to highlight that this type of
      substitution does not facilitate good chemotaxis, although it elicits both
      superoxide anion production and particularly lysozyme release, in some cases even
      more potent than the parent fMLP-OMe, if the hydrophilicity is associated with
      steric hindrance.

PMID- 11576333
TI  - The influence of steric interactions on the conformation and biology of oxytocin.
      Synthesis and analysis of penicillamine(6)-oxytocin and penicillamine(6)-5-tert
      butylproline(7)-oxytocin analogs.
AB  - Six [Pen(6)]oxytocin analogs were synthesized by substituting penicillamine for
      cysteine in oxytocin, [Mpa(1)]oxytocin, [dPen(1)]oxytocin, [5-t
      BuPro(7)]oxytocin, [Mpa(1), 5-t-BuPro(7)]oxytocin and [dPen(1), 5-t
      BuPro(7)]oxytocin. When tested in the uterotonic test in vitro [Pen(6)]oxytocin,
      [Pen(6), 5-t-BuPro(7)]oxytocin, [Mpa(1), Pen(6)]oxytocin and [Mpa(1), Pen(6), 5-t
      BuPro(7)]oxytocin, all were found to possess both agonistic and antagonistic
      properties. Their agonistic potency ranged from negligible (0.08 IU/mg) to low
      (5.85 IU/mg) and their antagonistic potency (pA2) was estimated to range from 6.6
      to 7.9. [dPen(1), Pen(6)]Oxytocin and [dPen(1), Pen(6), 5-t-BuPro(7)]oxytocin
      were found to be pure antagonists with similarly high pA2 values of approximately
      8.2. Replacement of proline by 5-tert-butylproline increased binding affinity by
      a factor of two in [Pen(6)]oxytocin and had no influence on the binding affinity
      of [Mpa(1), Pen(6)]oxytocin and [dPen(1), Pen(6)]oxytocin. Assignment of the
      proton signals for prolyl amide cis- and trans-isomers by NMR experiments in
      water indicated that the Pen(6)-5-tert-BuPro(7) peptide bond cis-isomer
      population was augmented relative to the prolyl peptides and measured,
      respectively, at 20, 35 and 35% in the 5-tert-butylproline(7) analogs of
      [Pen(6)]oxytocin, [Mpa(1), Pen(6)]oxytocin and [dPen(1), Pen(6)]oxytocin. This
      augmentation in cis-isomer population was correlated with a 21-fold reduction in
      the agonistic potency and 2-fold augmentation in antagonistic potency for
      [Pen(6), 5-t-BuPro(7)]oxytocin relative to [Pen(6)]oxytocin. Augmentation of cis
      isomer population was also correlated to reduced agonist potency without effect
      on antagonism on conversion of [Mpa(1), Pen(6)]oxytocin to [Mpa(1), Pen(6), 5-t
      BuPro(7)]oxytocin. In the potent oxytocin antagonist, [dPen(1), Pen(6)]oxytocin,
      substitution of 5-tert-butylproline for proline augmented the cis-isomer
      population without affecting antagonistic potency. The synthesis and evaluation
      of [Pen(6)]oxytocin and [Pen(6), 5-t-BuPro(7)]oxytocin analogs 1-6 indicated that
      steric interactions influenced agonist and antagonist activity by modifying
      peptide conformation. Augmentations in the prolyl cis-isomer population caused by
      5-tert-butylproline occurred concurrently with enhanced or maintained
      antagonistic potency and binding affinity and reduced agonistic potency.

PMID- 11576335
TI  - Difficulties in understanding human "acute tubular necrosis": limited data and
      flawed animal models.
AB  - This review summarizes the current understanding of the renal biopsy in "acute
      tubular necrosis" and the attempts to mimic this phenomenon in animal models.
      Paradoxically, only very limited necrosis is present in the biopsy of patients
      with this condition and differences in biopsies of patients with sustained and
      recovering renal failure cannot be clearly defined. The small amount of material
      examined, the variation in timing of the biopsy, the ability of the nephron to
      recover from sublethal injury, and the complexity of the clinical situation
      compound the difficulties in understanding this condition. Morphological findings
      in the animal studies are not equivalent to those in the human biopsy of "acute
      tubular necrosis," because they either have too much proximal tubular necrosis
      (ischemia-reflow model) or show severe injury to distal nephron segments (distal
      nephron model), the degree of which has not been clearly documented, as yet, in
      human material. The direct relevance of animal models in part may be tested by
      new noninvasive methods that define and quantify excreted proteins that reflect
      nephron injury or measure the status of renal oxygenation by radiological imaging
      techniques. Finally, it may be time to re-examine the morphology of "acute
      tubular necrosis," utilizing new techniques that illustrate induction of heat
      shock proteins, sublethal and apoptotic cellular injury, and alteration of gene
      expression.

PMID- 11576336
TI  - Further evidence for linkage of autosomal-dominant medullary cystic kidney
      disease on chromosome 1q21.
AB  - BACKGROUND: Autosomal-dominant medullary cystic kidney disease (ADMCKD) is
      characterized by the development of cysts at the corticomedullary border of the
      kidneys. It resembles nephronophthisis (NPH) with an autosomal-recessive mode of
      inheritance. Genetic linkage has been shown either on chromosome 1q21 (ADMCKD1)
      or 16p12 (ADMCKD2), and families exist who are not linked to the aforementioned
      loci. No disease-causing gene underlying this disorder has been reported.
      METHODS: The Finnish Transplantation Register and hospital records were searched
      to identify all of the ADMCKD families in the Finnish population. Detailed
      clinical information of the patients was collected. Linkage analysis was used to
      study whether the Finnish families originating from a homogeneous population
      showed genetic linkage to the ADMCKD1 or ADMCKD2 loci. Also, the coding region of
      a strong candidate gene, natriuretic peptide receptor A (NPRA), located on the
      chromosome 1q21 critical region, was sequenced using polymerase chain reaction
      sequencing with an ABI 377XL Automated DNA sequencer (Applera Corp., Norwalk, CT,
      USA). RESULTS: Five of the six families showed linkage to the previously
      identified region of chromosome 1q21. Family 6 with hyperuricemia as a prominent
      clinical feature was linked to neither of the ADMCKD loci. Wide interfamiliar and
      intrafamiliar variability in the clinical picture of the patients was detected.
      The NPRA gene mutation was excluded as a causative gene by sequencing.
      CONCLUSION: This study locates the gene for ADMCKD1 close to a marker D1S1595 in
      a region <5 cM, and further confirms the existence of at least three loci for the
      medullary cystic kidney disease. Heterogeneity of the symptoms complicates the
      clinical diagnosis and classification of the patients. Further studies are needed
      to identify the disease-causing gene.

PMID- 11576337
TI  - Confirmation of a gene locus for medullary cystic kidney disease (MCKD2) on
      chromosome 16p12.
AB  - BACKGROUND: Autosomal-dominant medullary cystic kidney disease (MCKD) is an
      interstitial nephropathy characterized by structural renal tubular defects that
      result in salt wasting and a reduction in urinary concentration. The condition
      has clinical and morphological similarities to autosomal-recessive juvenile
      nephronophthisis. Two genes predisposing to MCKD have been localized. MCKD1 on
      chromosome 1q21 was localized in two Cypriot families, and MCKD2 on chromosome
      16p12 was localized in a single Italian family. We have evaluated a large Welsh
      MCKD family for linkage at these two loci. METHODS: Clinical data and DNA samples
      were collected from affected family members. Polymorphic microsatellite markers
      spanning the critical regions on chromosome 1 and chromosome 16 that encompass
      MCKD1 and MCKD2 were analyzed. Two-point and multipoint LOD scores were
      calculated. RESULTS: The family fulfilled previously published criteria for the
      diagnosis of MCKD, but hyperuricemia and gout were not prominent features. Twenty
      one affected individuals were identified. Mean age at death or end-stage renal
      disease was 47 years (37 to 60). Linkage and haplotype analysis generated
      strongly negative results at MCKD1 on chromosome 1q21 (two-point LOD score = 
      5.32). Strong evidence of linkage to MCKD2 was generated with a maximum multi
      point LOD score of 3.75. CONCLUSION: These results provide the first independent
      confirmation of a gene predisposing to MCKD on chromosome 16p12 and indicate that
      mutation of this gene is not restricted to a single family or population. The
      absence of hyperuricemia and gout in our family indicates that these are not
      obligatory features of MCKD2 mutations.

PMID- 11576338
TI  - A novel inhibitor of tumor necrosis factor-alpha converting enzyme ameliorates
      polycystic kidney disease.
AB  - BACKGROUND: Transforming growth factor-alpha (TGF-alpha) expression is abnormal
      in polycystic kidney disease. We previously demonstrated that blockade of the
      epidermal growth factor receptor (EGFR), the receptor for TGF-alpha,
      significantly slowed disease progression in the bpk murine model of autosomal
      recessive kidney disease (ARPKD). In the present study, kidney TGF-alpha
      expression in this model is characterized, and the therapeutic potential of
      inhibiting TGF-alpha in ARPKD is examined using a novel inhibitor of tumor
      necrosis factor-alpha converting enzyme (TACE), the metalloproteinase that
      cleaves membrane-bound TGF-alpha to release the secreted ligand. METHODS:
      Immunohistochemistry (IH) and Western analysis were performed on kidneys from
      cystic bpk mice and noncystic littermates at postnatal days 7, 14, and 21. Bpk
      mice and normal controls were treated with WTACE2, a competitive inhibitor of
      TACE, from day 7 until day 21, and the effects on kidney histology and renal
      function were assessed. RESULTS: Increased TGF-alpha expression by IH was
      demonstrated in the proximal tubules (PT) at postnatal day 7 and collecting
      tubules (CT) by day 21. A parallel increase in kidney TGF-alpha expression was
      demonstrated by Western analysis. Treatment of cystic bpk mice with WTACE2
      resulted in a 43% reduction in kidney weight to body weight ratio (11.2 vs.
      19.7%), improved cystic index (3.2 vs. 4.8), reduced cystic CT to PT ratio (1.2
      vs. 8), and a greater than 30% reduction in BUN and serum creatinine.
      CONCLUSIONS: These findings support the pathophysiological role of the TGF
      alpha/EGFR axis in murine ARPKD and demonstrate that inhibition of TGF-alpha
      secretion has therapeutic potential in PKD.

PMID- 11576339
TI  - Dipyridamole inhibits TGF-beta-induced collagen gene expression in human
      peritoneal mesothelial cells.
AB  - BACKGROUND: Peritoneal matrix accumulation is characteristic of peritoneal
      fibrosis (PF). Continuous ambulatory peritoneal dialysis (CAPD) patients who had
      persistent transforming growth factor-beta (TGF-beta) in their drained effluent
      had an increased risk of PF. We previously reported that TGF-beta stimulates the
      expression of types I and III collagen mRNA in cultured human peritoneal
      mesangial cells (HPMCs), which may predispose them to develop PF. Pharmacological
      interventions to attenuate TGF-beta-stimulated matrix accumulation in HPMC may
      have therapeutic potential for the treatment of PF. The SMAD family and the
      extracellular signal-regulated protein kinase (ERK1/2, p44/p42) pathways have
      been shown to participate in TGF-beta signaling. Our current study identified
      these signal pathways in HPMCs and investigated the molecular mechanisms involved
      in the inhibitory effects of dipyridamole on TGF-beta-induced collagen gene
      expression in HPMCs. METHODS: HPMCs were cultured from human omentum by an enzyme
      digestion METHOD: Expression of collagen alpha1(I) mRNA was determined by
      Northern blotting. The SMAD proteins and the ERK1/2 activity were determined by
      Western blotting. RESULTS: TGF-beta-stimulated collagen alpha1(I) mRNA expression
      of HPMC was inhibited by dipyridamole in a dose-dependent manner. Smad2 and
      ERK1/2 were activated in response to TGF-beta; however, TGF-beta had little
      effect on the protein expression of Smad4. The addition of PD98059, which blocked
      activation of ERK1/2, suppressed TGF-beta-induced collagen alpha1(I) mRNA
      expression in a dose-dependent manner. At a concentration that inhibited collagen
      gene expression (17 microg/mL), dipyridamole suppressed ERK1/2 activation by TGF
      beta. In contrast, the same concentration of dipyridamole had no effect on TGF
      beta-induced activation of Smad2. CONCLUSION: Dipyridamole inhibits TGF-beta
      induced collagen gene expression in HPMC through modulation of the ERK pathway.
      Our study of dipyridamole may provide therapeutic basis for clinical applications
      in the prevention of PF.

PMID- 11576340
TI  - Effects of C-peptide on glomerular and renal size and renal function in diabetic
      rats.
AB  - BACKGROUND: Strict glycemic control and antihypertensive treatment may decrease
      but not eliminate the risk of progressive nephropathy in diabetic patients. C
      peptide has been shown to exert beneficial effects on complications, including
      incipient nephropathy, in type 1 diabetes. METHODS: Renal effects of 14 days of
      intravenous infusion of C-peptide or NaCl (placebo) were studied in three groups
      of rats: one nondiabetic NaCl-treated (normal, N = 7), one streptozotocin
      diabetic NaCl-treated (D-placebo, N = 7), and one streptozotocin diabetic C
      peptide-treated group (D-C-p, N = 7). Metabolic data and albuminuria were
      measured in metabolic cages every fourth day. After 14 days, the glomerular
      filtration rate (GFR) was measured by inulin clearance and available renal
      functional reserve (RFR) by glycine infusion, whereupon one kidney was perfusion
      fixed for morphological studies. RESULTS: Glucose levels were 36.7 +/- 1.3 and
      34.0 +/- 1.7 mmol/L in the D-placebo and D-C-p groups, respectively. The D
      placebo group presented a 32% (P < 0.001) larger glomerular volume than the D-C-p
      group. The D-placebo group also presented a significantly larger renal weight
      than the normal group in contrast to the D-C-p group. Urinary albumin excretion
      increased in the D-placebo group in contrast to the other groups. GFR was 1.72 +/
      0.12 mL/min (normal), 3.73 +/- 0.19 mL/min (D-placebo, P < 0.001 vs. normal) and
      2.16 +/- 0.16 mL/min (D-C-p, nonsignificant vs. normal). Available RFR was 93 +/-
      25% (normal), 10 +/- 4% (D-placebo, P < 0.05 vs. normal) and 57 +/- 13% (D-C-p,
      nonsignificant vs. normal) of basal GFR. CONCLUSIONS: Physiological doses of
      homologous C-peptide prevent the development of glomerular hypertrophy,
      albuminuria, and glomerular hyperfiltration in rats with experimentally induced
      diabetes.

PMID- 11576341
TI  - Role of aquaporin-2 gene expression in hyponatremic rats with chronic vasopressin
      induced antidiuresis.
AB  - BACKGROUND: In a state of chronic arginine vasopressin (AVP) excess, the action
      of antidiuresis has been attenuated, resulting in some water diuresis. This state
      has been termed an "AVP escape" phenomenon. The present study was designed to
      determine what mechanisms underlie this attenuation in renal concentrating
      ability, which is found in chronic AVP excess, both in the presence and absence
      of volume expansion. METHODS: Two groups of experimental rats were established.
      One group received solid chow with water ad libitum. The second group received
      chow, which was offered as a liquid diet. Both groups received subcutaneous
      administration of 1-deamino-8-D-arginine vasopressin (dDAVP) at 5 ng/h for the
      entire observation period of one week. Over the course of the observation period,
      tissue levels of aquaporin-2 (AQP-2) mRNA and protein were measured. Levels of
      AVP V2 receptor were monitored, both by measuring mRNA levels and by ligand
      binding studies using [3H]AVP. Tissue levels of cAMP also were determined.
      RESULTS: Experimental rats with the syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH) had severe hyponatremia below 120 mmol/L, and
      impaired urinary concentrating ability, during the seven-day observation period.
      In contrast, the dDAVP-excess rats, given solid chow, maintained maximally
      concentrated urine and normal levels of serum sodium. The down-regulation of AVP
      V2 receptor function was comparable in the two groups. The maximal binding
      capacity (Bmax) fell to the nadir on day 2 and was thereafter suppressed at
      approximately 60% of control rats during the experiment. Up-regulation of AQP-2
      mRNA expression was found, but this up-regulation was significantly less in the
      SIADH rats compared with the dDAVP-excess rats (153.5 +/- 29.8% vs. 323.7 +/-
      23.8% on day 7, P < 0.05). This differential response between these two groups
      was affirmed by measured differences in AQP-2 protein levels, both in tissue and
      in urinary excretion. CONCLUSIONS: These results indicate that the attenuated
      regulation of the AQP-2 gene leads to the decrease in urinary concentrating
      ability in the experimental SIADH rats, suffering from hypervolemic state,
      compared with the normonatremic rats receiving AVP. Either hypervolemia or
      hypotonicity may diminish the post-receptor signaling of AVP in renal collecting
      duct cells, under the chronic AVP excess state found in SIADH.

PMID- 11576342
TI  - Regulation of vitamin D-1alpha-hydroxylase in a human cortical collecting duct
      cell line.
AB  - BACKGROUND: Recent studies have shown that renal expression of 25-hydroxyvitamin
      D3-1alpha-hydroxylase (1alpha-OHase) is not restricted to proximal tubules. To
      investigate the significance of this expression, we characterized the regulation
      of 1alpha-OHase expression and activity in a human cortical collecting duct cell
      line (HCD). METHODS: Expression of 1alpha-OHase mRNA and protein was assessed by
      reverse transcription-polymerase chain reaction (RT-PCR) and Western blot
      analyses. Enzyme activity was quantified using 25-hydroxyvitamin D3 as the
      substrate; conversion to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 24,25
      dihydroxyvitamin D3 was then determined by thin-layer chromatography. RESULTS:
      HCD cells expressed mRNA and protein for 1alpha-OHase. However, basal 1,25(OH)2D3
      production was lower than that observed in proximal tubule HKC-8 cells. In both
      cell lines, synthesis of 1,25(OH)2D3 was increased by forskolin, parathyroid
      hormone, and low calcium medium. Conversely, treatment with 1,25(OH)2D3 itself
      decreased 1alpha-OHase activity. This effect was more pronounced in HCD cells,
      which also demonstrated significantly higher levels of 24-hydroxylase activity.
      The most striking induction of 1alpha-OHase activity was observed in the HCD
      cells following incubation with lipopolysaccharide, which was coincident with the
      expression of mRNA for both CD14 and Toll-like receptor 4. CONCLUSIONS: These
      results highlight the capacity for synthesis of 1,25(OH)2D3 in cells from more
      distal areas of the nephron. However, more sensitive feedback regulation and
      immune induction of 1alpha-OHase in the HCD cells suggest a more localized role
      for 1,25(OH)2D3 production in the distal nephron.

PMID- 11576343
TI  - Increased expression of heparanase in puromycin aminonucleoside nephrosis.
AB  - BACKGROUND: The beta-D-endoglycosidase heparanase has been proposed as an
      important contributor to loss of glomerular charge in proteinuria. Expression of
      heparanase was, therefore, determined in acute puromycin aminonucleoside (PAN)
      nephrosis. METHODS: A rabbit polyclonal antibody was produced against a 17-amino
      acid peptide derived from the predicted amino acid sequence of heparanase. The
      antibody was validated by Western blot. Immunohistochemical staining and Western
      blotting were used to localize heparanase protein in normal kidneys and kidneys
      from rats with PAN nephrosis. Northern blot analysis was used to determine mRNA
      expression. RESULTS: Immunohistochemical staining showed that heparanase protein
      was localized to tubular cells in the distal convoluted tubules, thick ascending
      limb of the loop of Henle, and transitional cell epithelium in normal kidney.
      Minimal expression was noted in normal glomeruli. Western blot analysis of
      protein from isolated normal glomeruli showed minimal expression of the 65 kD
      proheparanase protein. A marked increase in the staining for heparanase was found
      at day 5 of the PAN nephrosis model, at approximately the time of onset of
      proteinuria, and at day 14. Expression was predominantly seen in podocytes. At
      day 5, only the 65 kD proheparanase species was identified, but at day 14, mature
      58 kD heparanase also was present. Northern blot analysis of sieved glomeruli at
      day 14 confirmed an increase in heparanase mRNA. The human podocyte cell line
      56/10A1 also produced both proheparanase and mature heparanase, suggesting that
      podocytes can activate heparanase without other cell types. CONCLUSION: The
      previously mentioned data confirm that the novel beta-D-endoglycosidase
      heparanase is up-regulated and activated in glomeruli from rats with proteinuria.
      Heparanase may be involved, therefore, in the loss of glomerular charge seen in
      proteinuria. Moreover, the presence of heparanase in normal tubules suggests that
      it may also be involved in cell migration or turnover.

PMID- 11576344
TI  - Vascular endothelial growth factor (VEGF121) protects rats from renal infarction
      in thrombotic microangiopathy.
AB  - BACKGROUND: Renal thrombotic microangiopathy, typified by the hemolytic uremic
      syndrome, is associated with endothelial cell injury in which the presence of
      cortical necrosis, extensive glomerular involvement, and arterial occlusive
      lesions correlates with a poor clinical outcome. We hypothesized that the
      endothelial survival factor vascular endothelial growth factor (VEGF) may provide
      protection. METHOD: Severe, necrotizing, thrombotic microangiopathy was induced
      in rats by the renal artery perfusion of antiglomerular endothelial antibody,
      followed by the administration of VEGF or vehicle, and renal injury was
      evaluated. RESULTS: Control rats developed severe glomerular and
      tubulointerstitial injury with extensive renal necrosis. The administration of
      VEGF significantly reduced the necrosis, preserved the glomerular endothelium and
      arterioles, and reduced the number of apoptotic cells in glomeruli (at 4 hours)
      and in the tubulointerstitium (at 4 days). The prosurvival effect of VEGF for
      endothelium may relate in part to the ability of VEGF to protect endothelial
      cells from factor-induced apoptosis, as demonstrated for tumor necrosis factor
      alpha (TNF-alpha), which was shown to be up-regulated through the course of this
      model of renal microangiopathy. Endothelial nitric oxide synthase expression was
      preserved in VEGF-treated rats compared with its marked decrease in the surviving
      glomeruli and interstitium of the antibody-treated rats that did not receive
      VEGF. CONCLUSIONS: VEGF protects against renal necrosis in this model of
      thrombotic microangiopathy. This protection may be mediated by maintaining
      endothelial nitric oxide production and/or preventing endothelial cell death.

PMID- 11576345
TI  - Glomerulosclerosis and progression: effect of subantihypertensive doses of alpha
      and beta blockers.
AB  - BACKGROUND: Uremia is characterized by inadequately increased sympathetic
      activity. Sympathetic overactivity is involved in the genesis of hypertension in
      uremia, but its potential role on progression has not been well investigated. To
      address this issue, the effect of subantihypertensive doses of an alpha blocker
      and a beta blocker, and their combination on renal morphology and on albuminuria
      were investigated in the model of the subtotally nephrectomized rat. METHODS:
      Male Sprague-Dawley rats were subjected to surgical ablation (SNX) or sham
      operation (sham). Three days after surgery groups were treated either with
      phenoxybenzamine (PBZ, 5 mg/kg body weight/day), metoprolol (MET, 150 mg/kg body
      weight/day) or their combination (PBZ 2.5 mg/kg body weight/day + MET, 50 mg/kg
      body weight/day). Renal morphology was evaluated after 12 weeks by quantitative
      histology, immunohistochemistry, and electron microscopy. Urine albumin excretion
      and kidney endothelin-1 (ET-1), platelet-derived growth factor (PDGF), and
      transforming growth factor-beta (TGF-beta) mRNA expression were assessed.
      RESULTS: Systolic blood pressure was significantly higher in all SNX groups
      compared with sham-operated controls with no difference in the SNX groups. The
      number of glomeruli per left kidney was reduced from 30,904 +/- 3212 to 17,480 +/
      2341 by SNX (-43.5%). Mean glomerular volume increased from 2.63 +/- 0.7 in
      untreated sham operated to 4.11 +/- 0.48 microm 3 x 10(6) in untreated SNX
      (56.3%). The glomerulosclerosis index did not change in SNX + PBZ rats, but was
      significantly lower in SNX + MET (0.56 +/- 0.14) and particularly SNX + PBZ + MET
      rats (0.49 +/- 0.11) than in untreated SNX (0.74 +/- 0.24). Glomerular capillary
      length density (LV) as a sensitive index of capillary obliteration was
      significantly lower in SNX and almost normalized in the three intervention
      groups. The same was true for the mean podocyte number per glomerulus. Glomerular
      ultrastructure in SNX was largely preserved by all treatments. The albumin
      excretion rate was significantly higher in untreated SNX than in sham; it was
      significantly lower in all treated SNX groups. CONCLUSION: The beneficial effect
      of non-hypotensive doses of alpha and beta blockers and their combination on
      renal morphology and albuminuria in the model of renal ablation argue for a blood
      pressure-independent role of sympathetic overactivity in the genesis of
      progression. In addition, the beneficial effect of adrenergic receptor blockade
      indicates that a substantial part is not mediated by sympathetic cotransmitters
      such as adenosine 5'-triphosphate (ATP) and neuropeptide Y (NPY).

PMID- 11576346
TI  - Restricted gammadelta T-cell receptor repertoire in IgA nephropathy renal
      biopsies.
AB  - BACKGROUND: We have previously reported that gammadelta T cells are involved in
      the progression of IgA nephropathy (IgAN) to renal failure. Our current study
      examined the diversity of the CDR3 region of the gammadelta T-cell receptor
      (TCR), and characterized the junctional sequences of gammadelta chain TCR
      transcripts from T cells infiltrating renal biopsies from patients with IgAN and
      in peripheral blood T cells (PBLs) from the same patients. METHOD: RNA extracted
      from renal biopsies and PBLs of IgAN patients (N = 15) was transcribed and then
      amplified with primers specific for the four Vgamma and six Vdelta families.
      Controls were renal biopsies from thin basement membrane disease (N = 6) and a
      sample from a kidney with suppurative pyelonephritis. CDR3 length spectratyping
      and sequencing of TCR gammadelta-chain were used to analyze the diversity of CDR3
      region of these receptors. RESULTS: CDR3 spectratyping of gammadelta TCR
      junctional diversity demonstrated that TCR gammadelta chains (Vgamma1-3 and
      Vdelta1-3) expressed by T cells from PBLs of IgAN patients and the infected
      kidney showed highly diverse junctional lengths that were broadly distributed. In
      contrast, the junctional lengths of Vgamma1 (Vgamma2, 3, 4, 5, and 8 genes) and
      Vdelta1 transcripts in the T cells infiltrating kidneys with IgAN were much more
      restricted than those of PBLs. Renal biopsies from thin basement membrane disease
      demonstrated no significant signal for any Vgamma or Vdelta family. Sequence
      analysis of Vgamma1 and Vdelta1 transcripts from those patients with restricted
      CDR3 spectratyping profiles confirmed oligoclonal expansion of gammadelta T cells
      infiltrating the kidneys in those IgAN patients and also revealed recurrent
      junctional amino acid motifs in the TCR Vdelta1 chain in the kidney with IgAN.
      CONCLUSION: The data show that gammadelta T cells infiltrating the kidneys of
      IgAN patients use a restricted subset of gammadelta T cells, indicating clonal
      expansion of individual gammadelta T cells in the kidneys with IgAN. The feature
      of recurrent junctional amino acid motifs in Vdelta1 T cells may indicate antigen
      driven selection.

PMID- 11576347
TI  - Aristolochic acid impedes endocytosis and induces DNA adducts in proximal tubule
      cells.
AB  - BACKGROUND: Aristolochic acid (AA), present in Aristolochia plants, appears to be
      the toxin responsible for Chinese herbs nephropathy (CHN), a rapidly progressive
      tubulointerstitial nephritis. One of the earliest sign of CHN is the urinary
      excretion of low-molecular-weight proteins (LMWP), suggesting that AA is toxic to
      proximal tubules (PT). METHODS: The effects of AA on PT functions including
      reabsorption of LMWP were investigated on the well-established opossum kidney
      (OK) cell line, a model for PT, and compared with those of the classical PT toxin
      cadmium chloride (CdCl2). RESULTS: OK cell monolayers internalized albumin and
      beta2-microglobulin by receptor-mediated endocytosis, both proteins apparently
      competing for the same receptor, a complex of megalin and cubulin. The process
      was significantly impaired by 24-hour preincubation with AA (10 or 20 micromol/L)
      or CdCl2 (15 micromol/L). Furthermore, 24-hour exposure to AA followed by its
      removal during one to six days led to a persistent inhibition of the uptake of
      albumin, in contrast to the substantial recovery observed after CdCl2 removal.
      Neither AA nor CdCl2 affected cell viability, Na+-glucose cotransport or total
      rate of protein synthesis. AA significantly decreased megalin expression and
      formed specific DNA adducts in OK cells, similar to those found in kidneys from
      CHN patients. CONCLUSIONS: The present data support the involvement of AA in the
      early PT dysfunction found in CHN; furthermore, they suggest a causal
      relationship between DNA adduct formation, decreased megalin expression, and
      inhibition of receptor-mediated endocytosis of LMWP.

PMID- 11576348
TI  - Nrf2-deficient female mice develop lupus-like autoimmune nephritis.
AB  - BACKGROUND: NF-E2-related factor 2 (Nrf2) is a basic leucine zipper
      transcriptional activator essential for the coordinate transcriptional induction
      of antioxidant enzymes and phase II drug metabolizing enzymes through the
      antioxidant response element/electrophile response element. The Nrf2-deficient
      mice were found to develop normally under standard laboratory conditions.
      However, upon closer examination, we found that aged female Nrf2-deficient mice
      displayed a shortened lifespan and developed severe glomerulonephritis. The
      present study investigated the glomerulonephritis findings in Nrf2-deficient
      mice. METHODS: To evaluate glomerular lesions of Nrf2-deficient mice,
      histological and functional analyses were performed. The amounts of serum
      immunoglobulins, anti-double-stranded (ds) DNA antibody, and lipid peroxidation
      using thiobarbituric acid reactive substances (TBARS) also were measured.
      RESULTS: Nrf2-deficient female mice over 60 weeks of age developed severe
      nephritis characterized by cellular proliferation, lobular formation, crescent
      formation, and subepithelial electron-dense deposits. In immunofluorescent
      assays, Nrf2-deficient female mice showed mesangial deposits and massive granular
      deposits of IgG, IgM, and C3 along the capillary walls. Higher serum levels of
      IgG, anti-dsDNA antibody, lower creatinine clearance, and slight splenomegaly
      also were found in Nrf2-deficient female mice. A higher concentration of TBARS
      also was found in Nrf2-deficient female mice. CONCLUSIONS: These data indicate
      that the aged Nrf2-deficient female mice develop lupus-like autoimmune nephritis
      and suggest that nrf2 is one of the genes determining susceptibility to
      autoimmune disease. Analysis of nephritis in the Nrf2-deficient female mouse may
      clarify the mechanisms leading to the development of lupus disease.

PMID- 11576349
TI  - LF15-0195 prevents the induction and inhibits the progression of rat anti-GBM
      disease.
AB  - BACKGROUND: LF15-0195 is a novel immunosuppressant that is currently in phase II
      clinical trials for the treatment of vasculitis. This study examined whether LF15
      0195 could suppress the induction and progression of rat anti-glomerular basement
      membrane (anti-GBM) glomerulonephritis. METHODS: Rapidly progressive
      glomerulonephritis was induced in primed rats by the administration of anti-GBM
      serum. In the first experiment, LF15-0195 was given daily by subcutaneous
      injection (days 0 to 14) to treat the induction of anti-GBM disease analyzed at
      day 14. In a second experiment, rats received LF15-0195 as an intervention
      treatment from days 7 to 28 (continuous therapy) or days 7 to 12 (pulse therapy)
      to treat the progression of disease assessed at day 28. RESULTS: Continuous LF15
      0195 treatment during the induction of anti-GBM disease (experiment 1) prevented
      proteinuria and loss of renal function, and markedly reduced histological kidney
      lesions and renal fibrosis. LF15-0195 also reduced kidney leukocyte infiltrate,
      urine excretion of interleukin-1beta (IL-1beta) and transforming growth factor
      beta (TGF-beta), and the serum antibody response, but not kidney deposition of Ig
      and C3. When LF15-0195 treatment was initiated at day 7, both continuous and
      pulse therapy partially inhibited disease progression by suppressing the loss of
      renal function, interstitial macrophage and T-cell accumulation, tubular cell
      proliferation, and renal fibrosis. CONCLUSION: LF15-0195 prevents the induction
      and suppresses the progression of rat anti-GBM disease through multiple
      mechanisms of action, suggesting that this drug may have significant therapeutic
      potential in human glomerulonephritis. The similar efficacy of continuous and
      pulse intervention treatment in this model indicates that short-term LF15-0195
      treatment may achieve optimal benefit without prolonged bone marrow suppression.

PMID- 11576350
TI  - Tubular NF-kappaB and AP-1 activation in human proteinuric renal disease.
AB  - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) and activated protein-1 (AP-1) are
      transcription factors that regulate many genes involved in the progression of
      renal disease. Recent data have shown that NF-kappaB is activated in tubules and
      glomeruli in various experimental models of renal injury. In vitro studies also
      suggest that proteinuria could be an important NF-kappaB activator. We therefore
      approached the idea that NF-kappaB may be an indicator of renal damage
      progression. METHODS: Paraffin-embedded renal biopsy specimens from 34 patients
      with intense proteinuria [14 with minimal change disease (MCD) and 20 with
      idiopathic membranous nephropathy (MN)] and from 7 patients with minimal or no
      proteinuria (IgA nephropathy) were studied by Southwestern histochemistry for the
      in situ detection of activated transcription factors NF-kappaB and AP-1. In
      addition, by immunohistochemistry, we performed staining for the NF-kappaB
      subunits (p50 and p65) and AP-1 subunits (c-fos, c-jun). By immunohistochemistry
      and/or in situ hybridization, the expression of some chemokines [monocyte
      chemoattractant protein-1 (MCP-1), RANTES, osteopontin (OPN)] and profibrogenic
      cytokines [transforming growth factor-beta (TGF-beta)], whose genes are regulated
      by NF-kappaB and/or AP-1, were studied further. RESULTS: NF-kappaB was detected
      mainly in the tubules of proteinuric patients, but rarely in nonproteinuric IgA
      nephropathy (IgAN) patients. In addition, there was a significant relationship
      between the intensity of proteinuria and NF-kappaB activation in MCD (r = 0.64, P
      = 0.01) and MN patients (r = 0.64, P < 0.01). Unexpectedly, patients with MCD had
      a significantly higher NF-kappaB tubular activation than those with MN (P <
      0.01). To assess whether there was a different composition of NF-kappaB protein
      components, immunostaining was performed for the NF-kappaB subunits p50 and p65.
      However, no differences were noted between MCD and MN patients. In those
      patients, there was a lower tubular activation of AP-1 compared with NF-kappaB.
      Moreover, a strong correlation in the expression of both transcription factors
      was observed only in MN (r = 0.7, P = 0.004). Patients with progressive MN had an
      overexpression of MCP-1, RANTES, OPN, and TGF-beta, mainly in the proximal
      tubules, while no significant expression was found in MCD patients. CONCLUSIONS:
      On the whole, our results show that a tubular overactivation of NF-kappaB and AP
      1 and a simultaneous up-regulation of certain proinflammatory and profibrogenic
      genes are markers of progressive renal disease in humans. Increased activation of
      solely NF-kappaB and/or AP-1 may merely indicate the response of tubular renal
      cells to injury.

PMID- 11576351
TI  - Ganglioside as an endogenous growth suppressor for glomerular mesangial cells.
AB  - BACKGROUND: Glomerular mesangial cells potentially secrete many growth-modulating
      substances that could regulate mesangial cell proliferation. To date, however,
      the properties of such factors have not been fully evaluated. METHODS: For that
      purpose, conditioned medium (CM) from mesangial cells was used for cross-feeding
      experiments. Cell proliferation was evaluated by 3H-thymidine incorporation assay
      and direct cell counting. The growth-regulatory molecule was further
      characterized using biochemical techniques. RESULTS: Cross-feeding this CM to
      mesangial cells in vitro, despite stimulation with platelet-derived growth factor
      (PDGF), effectively suppressed the cells' synthesis of DNA in a dose-dependent
      manner. The inhibitory substance derived from mesangial cells was less than 3 kD
      in molecular mass, was heat stable, and was insensitive to proteinase K. After
      neuraminidase digestion, this inhibitory activity was lost. These data indicated
      that the inhibiting substance bore the typical features of gangliosides, which
      are multifunctional glycolipids that reside in cell membrane. Gangliosides were
      abundant in the CM from mesangial cells, as detected by metabolic radiolabeling
      and thin-layer chromatography (TLC). This result suggested that mesangial cells
      constitutively shed gangliosides. The growth suppressive activity in the CM was
      blunted when mesangial cells were pretreated with the ganglioside synthesis
      inhibitor d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol-HCl (d-threo
      PDMP; 20 micromol/L) in accordance with the decreased ganglioside content in
      cells. Finally, gangliosides isolated from CM of mesangial cells suppressed PDGF
      induced DNA synthesis of mesangial cells. CONCLUSIONS: These results suggest that
      mesangial cells constitutively shed gangliosides that then suppress the division
      of these cells in an autocrine-like manner.

PMID- 11576352
TI  - Expression of rat thick limb Na/H exchangers in potassium depletion and chronic
      metabolic acidosis.
AB  - BACKGROUND: Regulation of renal transporter expression has been shown to support
      adaptation of transporter activities in several chronic situations. Basolateral
      and apical Na/H exchangers (NHE) in medullary thick ascending limb (MTAL) are
      involved in NH4+ and HCO3+ absorption, respectively. The NH4+ absorption rate in
      Henle's loop is increased in chronic metabolic acidosis (CMA) and potassium
      depletion (KD), which may be secondary to the increased NH4+ concentration in
      luminal fluid and/or to an increased NH4+ absorptive capacity of MTAL. HCO3-
      absorptive capacity in Henle's loop is increased in CMA and decreased in
      metabolic alkalosis, but is unchanged in KD despite the presence of metabolic
      alkalosis. The present study compared the effects of NH4Cl-induced CMA and KD on
      the expression of basolateral NHE-1 and the effect of KD on the expression of
      apical NHE-3 in MTAL. METHODS: NHE-1 and NHE-3 mRNAs and proteins were assessed
      by a competitive reverse transcription-polymerase chain reaction (RT-PCR) method
      and semiquantitative immunoblots, respectively, in MTAL-purified suspensions from
      rats with CMA and KD. RESULTS: NHE-1 protein abundance was similarly increased
      (approximately 90%) at two and five weeks of KD, while NHE-1 mRNA amount in MTAL
      cells was increased at two weeks of KD and returned to normal values by five
      weeks of KD. In contrast, NHE-1 mRNA and protein abundance did not change in CMA.
      NHE-3 protein abundance remained unchanged in both two and five weeks of KD,
      while NHE-3 mRNA was unchanged by two weeks of KD and reduced by approximately
      50% at five weeks of KD. CONCLUSIONS: The results suggest the following: (1) in
      KD, where the increased NH4+ concentration of luminal fluid that favors NH4+
      absorption is counterbalanced by a decrease in BSC1 expression and activity, the
      increased NHE-1 expression may support an increased MTAL NH4+ absorptive capacity
      in CMA, NHE-1 expression is not specifically regulated and remains unchanged,
      suggesting that the increase in NH4+ concentration in luminal fluid is the main
      determinant of increased NH4+ absorption in MTAL. (2) In KD, NHE-3 expression did
      not decrease despite the presence of metabolic alkalosis, in agreement with the
      unchanged HCO3- absorptive capacity of Henle's loop.

PMID- 11576353
TI  - Preeclampsia and maladaptation to pregnancy: a role for atrial natriuretic
      peptide?
AB  - BACKGROUND: The majority of women with a history of preeclampsia have either an
      underlying thrombophilic disorder or a vascular disorder. In this study, we
      tested the hypothesis that only the latter condition predisposes for abnormal
      hemodynamic adaptation to pregnancy. METHODS: Thirty-seven formerly preeclamptic
      subjects were subdivided into a hypertensive (HYPERT, N = 10), a normotensive
      thrombophilic (THROMB, N = 13) and a normotensive nonthrombophilic subgroup
      (NONTHROMB, N = 14). In these women and in 10 normal parous controls, the
      following variables were measured at least five-months postpartum at day 5 (+/-2)
      of the menstrual cycle and again at five- and seven-weeks amenorrhea in the next
      pregnancy: mean arterial pressure, heart rate, cardiac output, central
      cardiovascular dimensions, plasma volume, glomerular filtration rate, effective
      renal plasma flow, 17-beta estradiol, progesterone, the hormones of the renin
      angiotensin-aldosterone (RAAS) axis, catecholamines and alpha-atrial natriuretic
      peptide. RESULTS: The early pregnancy rise in cardiac output, renal variables,
      RAAS activity, and plasma volume was comparable in all groups. However, the
      HYPERT and NONTHROMB subgroups differed from controls by a lower plasma volume in
      the prepregnant state. In addition, only the women in these two subgroups
      responded to pregnancy by a rise in circulating alpha-atrial natriuretic peptide.
      In addition, at seven weeks, in the subjects belonging to the HYPERT and
      NONTHROMB subgroups, plasma volume was the lowest and correlated inversely with
      the concomitant circulating level of alpha-atrial natriuretic peptide.
      CONCLUSION: The hemodynamic adaptation to pregnancy in the HYPERT and NONTHROMB
      subgroups differs from that in THROMB and controls by an early pregnancy rise in
      alpha-atrial natriuretic peptide. As a consequence, the early pregnancy plasma
      volume expansion in the NONTHROMB and HYPERT subgroups is less than in normal
      parous controls.

PMID- 11576354
TI  - Effects of enhanced oxygen release from hemoglobin by RSR13 in an acute renal
      failure model.
AB  - BACKGROUND: Acute renal failure is believed to be caused, in some circumstances,
      by impaired oxygen delivery to the outer medulla. This study examined the effect
      of RSR13, a synthetic allosteric modifier of hemoglobin oxygen-binding affinity,
      on renal function in a setting of acute renal failure in rats. METHODS: An in
      vivo model of acute renal failure in the rat produced by reduced renal mass, salt
      restriction, volume depletion, prostaglandin inhibition, and radiocontrast
      administration was used. A computer-based simulation of oxygen tensions along the
      nephron was utilized to interpret the findings. Mechanistic studies were
      subsequently performed using oxygen-sensitive electrodes and 31P nuclear magnetic
      resonance (NMR) spectroscopy to define the effect of RSR13 on renal function in
      the setting of compromised acute renal failure. RESULTS: RSR13 did not attenuate
      acute renal failure in this model; rather, serum creatinine increased to a
      greater degree in the RSR13-treated rats than in rats receiving saline vehicle as
      the control (P < 0.05). Simulations explained this finding under conditions of
      severe medullary hypoxia. Mechanistic studies demonstrated marked worsening of
      medullary hypoxia following RSR13 under conditions similar to our experimental
      model. Furosemide pretreatment to reduce the imbalance between oxygen supply and
      demand markedly attenuated the basal-medullary hypoxia produced in the presence
      of indomethacin and RSR13 (P < 0.01). Additionally, 31P NMR studies demonstrated
      renal adenosine 5'-triphosphate (ATP) depletion in rats with acute renal failure
      treated with RSR13 (45% decrease, P < 0.01); again, this effect of RSR13 was
      completely prevented by pretreatment with furosemide. CONCLUSIONS: Under
      conditions of severe renal medullary hypoxia, induced in part by indomethacin
      mediated reductions in outer medullary blood flow, the administration of RSR13
      can exacerbate acute renal dysfunction. However, reducing the rate of oxygen
      consumption by inhibiting sodium transport with furosemide pretreatment or post
      treatment appears to be functionally protective.

PMID- 11576355
TI  - Anti-B7-1 blocks mononuclear cell adherence in vasa recta after ischemia.
AB  - BACKGROUND: Blocking the costimulatory pathway by CTLA-4 Ig, reactive with both
      B7-1 and B7-2 costimulatory molecules, protects the kidney during acute
      ischemia/reperfusion injury. This study investigated whether and how B7-1 and/or
      B7-2 proteins are involved in renal ischemia/reperfusion injury (IRI). METHODS:
      Uninephrectomized rats were submitted to warm renal ischemia (30 min) and
      received control monoclonal antibody (mAb; 17E3), anti-B7-1 (3H5), anti-B7-2
      (24F), a combination of anti-B7-1/B7-2, or CTLA-4 Ig. Renal function, morphology,
      and the kinetics of inflammatory cells were studied for a ten-day period. Binding
      sites of the injected antibodies were detected by secondary staining with anti
      mouse Ab. RESULTS: Compared with controls, acute renal failure (ARF) in the anti
      B7-1 group was attenuated both functionally and morphologically. Anti-B7-1/B7-2
      and CTLA-4 Ig also were protective in IRI. ARF was not altered by anti-B7-2
      treatment. Two hours after reperfusion, B7-1 was expressed along the endothelial
      cells of the ascending vasa recta. Expression of B7-1 increased over time during
      the first 24 hours and decreased thereafter. Two hours after reperfusion,
      adherence/accumulation of T cells and monocytes/macrophages was found in the vasa
      recta of the ischemic kidney. Anti-B7-1-treated animals had fewer T cells and
      monocytes/macrophages in the vasa recta compared with controls. Leukocyte
      accumulation in these vessels after anti-B7-2 treatment was not different from
      IRI controls. CONCLUSION: These observations strongly support the key role of the
      B7-1 protein in the protection of renal IRI through inhibition of T cell and
      monocyte adherence at the level of the ascending vasa recta.

PMID- 11576356
TI  - Dinucleotide repeat polymorphism of matrix metalloproteinase-9 gene is associated
      with diabetic nephropathy.
AB  - BACKGROUND: Although genetic susceptibility has been proposed as an important
      factor for the development and progression of diabetic nephropathy, the
      definitive gene has not been identified. To identify the genetic marker for
      diabetic nephropathy, we examined the association between the (A-C)n dinucleotide
      repeat polymorphism upstream of the matrix metalloproteinase-9 (MMP-9) gene and
      diabetic nephropathy in a group of Japanese patients with type 2 diabetes.
      METHODS: Patients were divided into three groups based on their urinary albumin
      excretion rate (AER) and the stage of diabetic retinopathy as follows:
      uncomplicated group (U), normal albuminuria (AER <20 microg/min) without
      proliferative retinopathy and with the duration of diabetes more than 20 years (N
      = 32); microalbuminuria group (M), 20 < or = AER < 200 microg/min (N = 155);
      overt nephropathy group (O), AER > or = 200 microg/min (N = 63). The region
      containing the dinucleotide repeat upstream of MMP-9 gene was amplified by
      polymerase chain reaction (PCR). The amplified products were analyzed with 7%
      formamide/urea acrylamide gel electrophoresis. The promoter constructs of the MMP
      9 gene were transfected with the CMV-beta-galactosidase construct into 293 cells
      using the liposome method. Twenty-four hours after transfection, cells were
      harvested, and luciferase and beta-galactosidase activities were measured.
      RESULTS: Nine alleles of the dinucleotide repeat polymorphism (17 to 25 repeats)
      were identified, and the frequency of each allele in diabetic subjects was not
      different from that in nondiabetic controls. The frequency of the allele
      containing 21 repeats (A21) was most abundant (42.4% in control and 45.6% in
      diabetic subjects), followed by the allele with 23 repeats (A23; 35.4% in control
      and 27.6% in diabetic subjects). The A21 allele was less frequent in M and O than
      U (O, 38.9%; M, 45.5%; U, 59.3%, chi2 = 7.18; P < 0.05, O vs. U), while the
      frequency of the alleles other than A21 was not different among each group. The
      calculated odds ratio for nephropathy in the noncarrier, heterozygote, or
      homozygote of A21 allele was 3.38, 1.97, and 0.2, respectively. Furthermore, the
      promoter assay for the MMP-9 gene revealed that the A21 allele had a higher
      promoter activity compared with other alleles. No significant correlation was
      observed between serum MMP-9 concentrations and the MMP-9 gene polymorphism.
      CONCLUSION: These results indicate that the patients with A21 allele of the MMP-9
      gene may be protected from the development and progression of diabetic
      nephropathy. Thus, the microsatellite polymorphism upstream of the MMP-9 gene
      could be a useful genetic marker for diabetic nephropathy.

PMID- 11576357
TI  - Autoregulated glomerular filtration rate during candesartan treatment in
      hypertensive type 2 diabetic patients.
AB  - BACKGROUND: Impaired autoregulation of the glomerular filtration rate (GFR)
      implies disturbances in the downstream transmission of the systemic blood
      pressure into the glomerulus, leading to capillary hypertension or hypotension
      dependent of the level of blood pressure. The impact on renal autoregulation of
      different antihypertensive drugs in animals has been elucidated, whereas
      information in humans is lacking. METHODS: A randomized, double-blind crossover
      study with candesartan cilexetil 16 mg o.d. and placebo was performed in 17
      hypertensive type 2 diabetic patients without nephropathy. Each treatment arm
      lasted four weeks. On the last day, GFR (single shot [51Cr] EDTA plasma clearance
      technique for 4 hours) was measured twice between 8 a.m. and 5 p.m., first
      without clonidine and then after an intravenous injection of clonidine 75 microg.
      Blood pressure (Takeda TM2420, A&D, Tokyo, Japan) was measured every ten minutes,
      and the urinary albumin excretion rate (UAER) was measured by ELISA during each
      GFR determination. RESULTS: Candesartan induced a mean (SE) reduction in mean
      arterial blood pressure (MABP) of 6 (2) mm Hg (P < 0.02) and had a tendency to
      reduce UAER (P = 0.07), while GFR remained unchanged (95 vs. 93 mL/min/1.73 m2).
      Clonidine reduced MABP with 17 (2) versus 16 (1) mm Hg during placebo versus
      candesartan 16 mg o.d., respectively (NS). GFR diminished in average from 95 (3)
      to 92 (4) mL/min/1.73 m2 with placebo (NS), and from 93 (3) to 89 (4) mL/min/1.73
      m2 during treatment with candesartan (NS). The mean difference (95% CI) in the
      changes in GFR between the examination with placebo and with candesartan was 0.1
      (-5.5 to 5.8) mL/min/1.73 m2 (NS). CONCLUSION: Candesartan reduces blood pressure
      without adversely altering the preserved ability to autoregulate GFR in
      hypertensive type 2 diabetic patients without nephropathy.

PMID- 11576358
TI  - Type of vascular access and mortality in U.S. hemodialysis patients.
AB  - BACKGROUND: Vascular access (VA) complications account for 16 to 25% of hospital
      admissions. This study tested the hypothesis that the type of VA in use is
      correlated with overall mortality and cause-specific mortality. METHODS: Data
      were analyzed from the U.S. Renal Data System Dialysis Morbidity and Mortality
      Study Wave 1, a random sample of 5507 patients, prevalent on hemodialysis as of
      December 31, 1993. The relative mortality risk during a two-year observation was
      analyzed by Cox-regression methods with adjustments for demographic and comorbid
      conditions. Using similar methods, cause-specific analyses also were performed
      for death caused by infection and cardiac causes. RESULTS: In diabetic mellitus
      (DM) patients with end-stage renal disease, the associated relative mortality
      risk was higher for those with arteriovenous graft (AVG; RR = 1.41, P < 0.003)
      and central venous catheter (CVC; RR = 1.54, P < 0.002) as compared with
      arteriovenous fistula (AVF). In non-DM patients, those with CVC had a higher
      associated mortality (RR = 1.70, P < 0.001), as did to a lesser degree those with
      AVG (RR = 1.08, P = 0.35) when compared with AVF. Cause-specific analyses found
      higher infection-related deaths for CVC (RR = 2.30, P < 0.06) and AVG (RR = 2.47,
      P < 0.02) compared with AVF in DM; in non-DM, risk was higher also for CVC (RR =
      1.83, P < 0.04) and AVG (RR = 1.27, P < 0.33). In contrast to our hypothesis that
      AV shunting increases cardiac risk, deaths caused by cardiac causes were higher
      in CVC than AVF for both DM (RR = 1.47, P < 0.05) and non-DM (RR = 1.34, P <
      0.05) patients. CONCLUSION: This case-mix adjusted analysis suggests that CVC and
      AVG are correlated with increased mortality risk when compared with AVF, both
      overall and by major causes of death.

PMID- 11576359
TI  - Correlates of acute renal failure in patients receiving parenteral amphotericin
      B.
AB  - BACKGROUND: While parenteral amphotericin B is an effective therapy for serious
      fungal infections, it frequently causes acute renal failure (ARF). This study
      identified correlates of ARF in amphotericin B therapy and used them to develop
      clinical prediction rules. METHODS: All 643 inpatients receiving parenteral
      amphotericin B therapy at one tertiary care hospital were included. Data
      regarding correlates were obtained both electronically and from manual chart
      review in a subsample of 231 patients. ARF was defined as a 50% increase in the
      baseline creatinine with a peak > or =2.0 mg/dL. RESULTS: Among 643 episodes, ARF
      developed in 175 (27%). In the larger group, the only independent correlate of
      ARF was male gender (OR = 2.2, 95% CI, 1.5 to 3.3). In the subsample (N = 231),
      independent correlates of ARF were maximum daily amphotericin dosage, location at
      the time of initiation of amphotericin therapy, and concomitant use of
      cyclosporine. These data were used to develop two clinical prediction rules. A
      rule using only data available at initiation of therapy stratified patients into
      groups with probability of ARF ranging from 15 to 54%, while a rule including
      data available during therapy (maximum daily dose) stratified patients into
      groups with probability of ARF ranging from 4 to 80%. CONCLUSIONS: Acute renal
      failure occurred in a quarter of the patients. Correlates of ARF at the beginning
      and during the course of amphotericin therapy were identified and then combined
      to allow stratification according to ARF risk. These data also provide evidence
      for guidelines for the selection of patients for alternative therapies.

PMID- 11576360
TI  - Improved assessment of bone turnover by the PTH-(1-84)/large C-PTH fragments
      ratio in ESRD patients.
AB  - BACKGROUND: The "intact" parathyroid hormone (PTH) assay recognizes PTH-(1-84) as
      well as amino terminally truncated PTH fragments, that is, large carboxyterminal
      PTH fragments (C-PTH fragments). The present study investigated whether the use
      of the plasma PTH-(1-84)/C-PTH fragment ratio enhances the noninvasive assessment
      of bone turnover in patients on dialysis. METHODS: Bone biopsies and blood
      samples for determinations of routine indices of bone turnover and PTH peptides
      were obtained in 51 adult patients on dialysis not treated with drugs affecting
      bone such as vitamin D or corticosteroids. Blood levels of large C-PTH fragments
      were calculated by subtracting PTH-(1-84) from "intact" PTH. Patients were
      classified according to their levels of bone turnover based on
      histomorphometrically obtained results of activation frequency. Prediction of
      bone turnover by the various blood indices was done by using proper statistical
      methods. In addition, hypercalcemia was induced by calcium gluconate infusion in
      a subset of patients, and levels of PTH-(1-84), "intact" PTH, and PTH-(1-84)/C
      PTH fragment ratio were determined. RESULTS: The PTH-(1-84)/C-PTH fragment ratio
      was the best predictor of bone turnover. A ratio> 1 predicted high or normal bone
      turnover (sensitivity 100%), whereas a ratio <1 indicated a high probability
      (sensitivity 87.5%) of low bone turnover. Calcium infusion resulted in decrease
      in PTH-(1-84)/C-PTH fragment ratio. CONCLUSIONS: The PTH-(1-84)/C-PTH fragment
      ratio predicts bone turnover with acceptable precision for biological
      measurements. Moreover, a change in serum calcium levels is one of the regulators
      of the relative amount of circulating PTH-(1-84) and its large C-PTH fragments.

PMID- 11576361
TI  - Renal and neurohormonal responses to increasing levels of lower body negative
      pressure in men.
AB  - BACKGROUND: The stimulation of efferent renal sympathetic nerve activity induces
      sequential changes in renin secretion, sodium excretion, and renal hemodynamics
      that are proportional to the magnitude of the stimulation of sympathetic nerves.
      This study in men investigated the sequence of the changes in proximal and distal
      renal sodium handling, renal and systemic hemodynamics, as well as the hormonal
      profile occurring during a sustained activation of the sympathetic nervous system
      induced by various levels of lower body negative pressure (LBNP). METHODS: Ten
      healthy subjects were submitted to three levels of LBNP ranging between 0 and 
      22.5 mm Hg for one hour according to a triple crossover design, with a minimum of
      five days between each level of LBNP. Systemic and renal hemodynamics, renal
      water and sodium handling (using the endogenous lithium clearance technique), and
      the neurohormonal profile were measured before, during, and after LBNP. RESULTS:
      LBNP (0 to -22.5 mm Hg) induced an important hormonal response characterized by a
      significant stimulation of the sympathetic nervous system and gradual activations
      of the vasopressin and the renin-angiotensin systems. LBNP also gradually reduced
      water excretion and increased urinary osmolality. A significant decrease in
      sodium excretion was apparent only at -22.5 mm Hg. It was independent of any
      change in the glomerular filtration rate and was mediated essentially by an
      increased sodium reabsorption in the proximal tubule (a significant decrease in
      lithium clearance, P < 0.05). No significant change in renal hemodynamics was
      found at the tested levels of LBNP. As observed experimentally, there appeared to
      be a clear sequence of responses to LBNP, the neurohormonal response occurring
      before the changes in water and sodium excretion, these latter preceding any
      change in renal hemodynamics. CONCLUSIONS: These data show that the renal sodium
      retention developing during LBNP, and thus sympathetic nervous stimulation, is
      due mainly to an increase in sodium reabsorption by the proximal segments of the
      nephron. Our results in humans also confirm that, depending on its magnitude,
      LBNP leads to a step-by-step activation of neurohormonal, renal tubular, and
      renal hemodynamic responses.

PMID- 11576362
TI  - Outcome of living unrelated (commercial) renal transplantation.
AB  - BACKGROUND: Due to inadequate cadaveric and living related organ supply, many end
      stage renal disease patients go to Third World countries for commercial
      transplantation, although the high risk of complications is well established and
      ethical arguments debate this practice. METHODS: The midterm outcome of 115
      patients who had been commercially transplanted in various countries and admitted
      to our center for post-transplant care and follow-up between 1992 and 1999 was
      retrospectively analyzed. Data considering the transplantation practice and post
      transplant course were collected from the patient files. Outcome of these
      patients was compared with those with a living related transplant performed at
      our center. RESULTS: The patients (91 male and 24 female; mean age of 42 +/- 12
      years) were transplanted in India (N = 106), Iraq (N = 7), and Iran (N = 2). The
      mean follow-up period was 64.5 +/- 23.9 months. Post-transplant course was
      complicated by numerous surgical and/or medical complications, and many of the
      latter were unconventional infections caused by malaria, invasive fungal
      infections, and pneumonia due to various opportunistic pathogens. Overall, 52
      patients still have functioning allografts, while 22 lost their grafts, 20 died,
      and 21 were lost to follow-up. Graft survival rates at two, five, and seven years
      were 84, 66, and 53%, respectively, for the study group, while it was 86, 78, and
      73% for living related transplantations performed at our center (P = 0.036).
      Patient survival rates for the same periods were 90, 80, and 74% for the study
      group and 90, 85, and 80% for the living related transplantations (P = 0.53).
      CONCLUSIONS: Besides the ongoing ethical debate, commercial transplantation
      carries a high risk of unconventional complications, and despite that the patient
      survival rate is comparable, graft survival is worse than conventional living
      related transplantations at the midterm.

PMID- 11576363
TI  - Proteinuria in obstructive sleep apnea.
AB  - BACKGROUND: Previous studies have reported an association between obstructive
      sleep apnea (OSA) and proteinuria, but are limited in their ability to assess
      proteinuria accurately, to adjust for confounders such as obesity, or to exclude
      confidently underlying renal disease in patients with OSA and nephrotic-range
      proteinuria. METHODS: The spot urine protein/creatinine ratio was measured in a
      prospective consecutive series of 148 patients referred for polysomnography who
      were not diabetic and had not been treated previously for OSA. The urine
      protein/creatinine ratio was compared across four levels of OSA severity, based
      on the frequency of apneas and hypopneas per hour: <5 (absent), 5 to 14.9 (mild),
      15 to 29.9 (moderate), and > or =30 (severe). RESULTS: The median level of urine
      protein/creatinine ratio in all categories of OSA was <0.2 (range 0.03 to 0.69;
      median 0.06 in patients with normal apnea hypopnea index, 0.06, 0.07, 0.07 in
      patients with mild, moderate, and severe OSA, respectively). Eight subjects had a
      urine protein/creatinine ratio greater than 0.2. Univariate analysis showed a
      significant association between urine protein/creatinine ratio and older age (P <
      0.0001), hypertension (P < 0.0001), coronary artery disease (P = 0.003), and
      arousal index (P = 0.003). Body mass index (P = 0.16), estimated creatinine
      clearance (P = 0.17), and apnea hypopnea index (P = 0.13) were not associated
      with the urine protein/creatinine ratio. In multiple regression analysis, only
      age and hypertension were independent positive predictors of the urine
      protein/creatinine ratio (P < 0.0001, R2 = 0.17). CONCLUSION: Clinically
      significant proteinuria is uncommon in sleep apnea. Nephrotic range proteinuria
      should not be ascribed to sleep apnea and deserves a thorough renal evaluation.

PMID- 11576364
TI  - Severity of renal vascular disease predicts mortality in patients undergoing
      coronary angiography.
AB  - BACKGROUND: Renal artery stenosis (RAS) is a relatively uncommon but potentially
      reversible cause of renal failure. In a previous report, we demonstrated that the
      presence of RAS is independently associated with mortality in a group of patients
      undergoing coronary angiography. Our current study expands on this cohort,
      investigating the effect of the severity of RAS on all-cause mortality. METHODS:
      A total of 3987 patients underwent abdominal aortography immediately following
      coronary angiography. For the purpose of survival analysis, significant RAS was
      defined as > or =75% narrowing in the luminal diameter. RESULTS: Significant RAS
      was present in 4.8% of patients studied and was bilateral in 0.8%. Factors
      associated with the presence of RAS included female gender, older age,
      hypertension, congestive heart failure, elevated serum creatinine, and congestive
      heart failure. The four-year unadjusted survivals for patients with and without
      significant RAS were 57 and 89%, respectively (P < 0.001). Using the Cox
      proportional hazards model, the factors independently associated with decreased
      survival were the presence of RAS, increased age, the severity of coronary artery
      disease, the presence of comorbid disease, reduced ejection fraction, symptoms of
      congestive cardiac failure, and the mode of treatment of coronary artery disease.
      In the multivariate model, the presence of RAS conferred a hazard ratio of 2.01
      (95% CI, 1.51 to 2.67, P < 0.001). We demonstrated an incremental effect on
      mortality according to the severity of RAS at baseline. Four-year adjusted
      survival for patients with 50%, 75%, and > or =95% stenosis was 70%, 68%, and
      48%, respectively. In addition, bilateral disease was associated with four-year
      survival of 47% as compared with 59% for patients with unilateral disease (P <
      0.001). The impact of RAS on survival remained robust regardless of the manner of
      treatment of coronary artery disease [that is, medical, percutaneous transluminal
      coronary angioplasty (PTCA), or coronary artery bypass graft (CABG)].
      CONCLUSIONS: In this patient population, the presence of RAS is a strong
      independent predictor of mortality. Increasing severity of RAS has an incremental
      effect on survival probability.

PMID- 11576365
TI  - Comorbidity assessment using the Index of Coexistent Diseases in a multicenter
      clinical trial.
AB  - BACKGROUND: The Hemodialysis (HEMO) Study is a multicenter trial designed to
      determine whether hemodialysis dose and membrane flux affect survival. Comorbid
      conditions are also important determinants of survival, and thus, an accurate and
      reliable method to assess comorbidity was required. Comorbidity was being
      assessed at baseline and annually in the HEMO Study using the Index of Coexistent
      Disease (ICED). We describe the instrument, its implementation in the HEMO Study,
      and the results of comorbidity assessment in the first 1000 randomized patients
      in the trial. METHODS: The ICED aggregated the presence and severity of 19
      medical conditions and 11 physical impairments within two scales: the Index of
      Disease Severity (IDS) and the Index of Physical Impairment (IPI). The final ICED
      score was determined by an algorithm combining the peak scores for the IDS and
      IPI. The range of the ICED was from 0 to 3, reflecting increasing severity.
      RESULTS: Study personnel at 15 clinical centers were trained to update and
      abstract data from the dialysis medical records. Availability of data, measures
      of construct validity, and measures of reliability were adequate; 99.8% and 60.6%
      of patients had comorbid conditions in at least one IDS or IPI category,
      respectively. The distribution of patients by ICED level was 0 (0.2%), 1 (34.9%),
      2 (31.2%), and 3 (33.7%). In multivariable analysis, the following factors were
      significantly associated with more severe comorbidity: older age, diabetes and
      other causes of renal disease, a lower level of education, employment status
      (unemployed and retired), longer duration of dialysis, and lower serum
      creatinine. There was a significant variation in the severity of comorbidity
      among clinical centers after adjustment for other factors. The R2 of the model
      was 25.3%, indicating that a substantial proportion of the variation in the ICED
      was not explained by these factors. CONCLUSIONS: We conclude that comorbidity
      assessment using the ICED is feasible in multicenter clinical trials of dialysis
      patients. There is a large burden of comorbidity in dialysis patients, which is
      not well explained by the cause of renal disease, demographic, and socioeconomic
      factors and common clinical and laboratory measurements. These variables should
      not be considered substitutes for comorbid conditions in case-mix adjustment.
      Comorbidity assessment is useful to describe the sample population, to improve
      the precision of the treatment effect, and to use possibly as an outcome
      measurement.

PMID- 11576366
TI  - Vancomycin-resistant enterococci colonization in patients at seven hemodialysis
      centers.
AB  - BACKGROUND: Vancomycin-resistant enterococci (VRE) are increasing in prevalence
      at many institutions, and are often reported in dialysis patients. We studied the
      prevalence of and risk factors for VRE at seven outpatient hemodialysis centers
      (three in Baltimore, MD, USA, and four in Richmond, VA, USA). METHODS: Rectal or
      stool cultures were performed on consenting hemodialysis patients during December
      1997 to April 1998. Consenting patients were recultured during May to July 1998
      (median 120 days later). Clinical and laboratory data and functional status (1 to
      10 scale: 1, normal function; 9, home attendant, not totally disabled; 10,
      disabled, living at home) were recorded. RESULTS: Of 478 cultures performed, 20
      (4.2%) were positive for VRE. Among the seven centers, the prevalence of VRE
      positive cultures varied from 1.0 to 7.9%. Independently significant risk factors
      for a VRE-positive culture were a functional score of 9 to 10 (odds ratio 6.9, P
      < 0.001), antimicrobial receipt within 90 days before culture (odds ratio 6.1, P
      < 0.001), and a history of injection drug use (odds ratio 5.4, P = 0.004).
      CONCLUSIONS: VRE-colonized patients were present at all seven participating
      centers, suggesting that careful infection-control precautions should be used at
      all centers to limit transmission. In agreement with previous studies, VRE
      colonization was more frequent in patients who had received antimicrobial agents
      recently, underscoring the importance of judicious antimicrobial use in limiting
      selection for this potential pathogen.

PMID- 11576367
TI  - Effect of renal center characteristics on mortality and technique failure on
      peritoneal dialysis.
AB  - BACKGROUND: Recent studies report decreased mortality in patients on peritoneal
      dialysis (PD) over time, suggesting that advances in PD have resulted in improved
      patient outcomes. Our investigation sought to assess the effect of renal center
      characteristics on mortality and technique failure (TF) rates. METHODS:
      Covariates of interest included center-specific cumulative number of PD patients
      treated, percentage of patients who initiated dialysis on PD, and academic
      status. Using data obtained from the Canadian Organ Replacement Register, the
      17,900 patients who received PD during the 1981 to 1997 period were studied.
      Mortality and TF rate ratios (RR) were estimated using Poisson regression,
      adjusting for age, gender, race, primary renal diagnosis, province, follow-up
      time, and type of PD. RESULTS: As the cumulative number of PD patients treated
      increased, covariate-adjusted mortality significantly decreased (P < 0.05); a
      weaker yet significant association was observed between number of PD patients
      treated and TF. As the percentage of patients initiating dialysis on PD
      increased, TF rates decreased significantly. No association was observed between
      center academic status and PD mortality or TF rates. CONCLUSIONS: These results
      imply that a center's experience with and degree of specialization toward PD
      impact strongly on PD outcomes. One hypothesis is that a center's propensity to
      exploit technical and non-technical advances in PD increases directly with these
      variables. It is also possible that, through experience, centers become more
      adept at identifying appropriate patients to receive PD. More detailed research
      is required to evaluate these hypotheses.

PMID- 11576368
TI  - Increase in plasma esterified F2-isoprostanes following intravenous iron infusion
      in patients on hemodialysis.
AB  - BACKGROUND: In epoetin-treated dialysis patients, currently iron is administered
      by the intravenous route to maintain optimum erythropoiesis. However, rapid
      infusion of iron in excess of transferrin binding capacity can lead to the
      availability of unbound iron that can theoretically catalyze peroxidation of
      lipids, such as low-density lipoprotein (LDL), which when oxidatively modified is
      proinflammatory and promotes atherogenesis. METHODS: To address this issue, our
      study used one of the most specific measures of lipid peroxidation available,
      namely gas chromatography/mass spectometry (GC/MS) analysis of F2-isoprostanes.
      Using a prospective design, blood samples were collected 15 minutes before (pre)
      and 30 minutes after (post) a one-hour infusion of 700 mg bolus of intravenous
      iron in 22 adult home-hemodialysis patients on a non-hemodialysis day. RESULTS:
      With iron-dextran infusion, serum iron markedly increased (mean +/- SE, 42 +/- 4
      vs. 311 +/- 92 microg/dL, P < 0.0001) and exceeded the transferrin saturation of
      100% in 22 out of 22 patients (pre 23 +/- 3 vs. post 165 +/- 8%, P < 0.0001).
      Plasma concentrations of free F2-isoprostanes did not change significantly
      following infusion of iron (pre 40 +/- 5 vs. post 39 +/- 6 pg/mL). However,
      levels of F2-isoprostanes esterified in plasma lipoproteins increased
      significantly in the postinfusion samples (pre 199 +/- 19 vs. post 233 +/- 25
      pg/mL, P < 0.004). Pre-infusion levels of serum iron correlated directly with pre
      infusion levels of esterified F2-isoprostanes (r = 0.56, P = 0.008), which
      persisted in the postinfusion period (r = 0.43, P = 0.04). However, there was no
      correlation between esterified F2-isoprostanes and serum ferritin levels. In the
      last four patients in whom blood samples were collected five hours after the
      intravenous iron infusion, there were further increases in esterified F2
      isoprostanes that very closely correlated with postinfusion serum iron levels (r
      = 0.99, P = 0.013). In a control study, the in vitro addition of iron dextran to
      blood samples did not increase free or esterified F2-isoprostanes, suggesting
      that the increase in esterified F2-isoprostanes seen in vivo after iron infusion
      in patients is not due to a procedural artifact. CONCLUSION: Collectively our
      data suggest that high levels of serum iron appearing soon after a large bolus of
      iron infusion is associated with significant, albeit modest, increases in levels
      of F2-isoprostanes esterified in plasma lipoproteins that tended to increase with
      time. Although it is uncertain whether this degree of lipid peroxidation may have
      deleterious effects, it may be sagacious to explore whether this can be prevented
      by slow infusion of frequent smaller doses of iron and, if necessary, along with
      administration of antioxidants.

PMID- 11576369
TI  - Comparison of transposed brachiobasilic fistulas to upper arm grafts and
      brachiocephalic fistulas.
AB  - BACKGROUND: Renewed interest in transposed brachiobasilic fistulas has occurred
      since the release of the National Kidney Foundation-Dialysis Outcomes Quality
      Initiative (NKF-DOQI) guidelines because it is an alternative method to achieve
      an upper arm fistula in patients who cannot achieve a functional brachiocephalic
      fistula. The objective of this study was to compare outcomes among transposed
      brachiobasilic fistulas, upper arm grafts, and brachiocephalic fistulas. METHODS:
      A cohort of patients with upper arm accesses was retrospectively identified.
      Access outcomes were determined from medical records and contact with physicians,
      dialysis providers, and patients. Primary outcome was thrombosis-free survival.
      Secondary outcomes were primary failure, time to use, risk of catheter-related
      bacteremia, need for intervention, incidence of access-related complications,
      cumulative, and functional patency. Group differences in age, sex, race,
      diabetes, peripheral vascular disease, and number of previous accesses were
      adjusted for in the analysis where appropriate. RESULTS: Transposed
      brachiobasilic fistulas, upper arm grafts, and brachiocephalic fistulas were
      compared in 59, 82, and 56 patients, respectively. Compared with transposed
      brachiobasilic fistulas, upper arm grafts were more likely to thrombose with an
      adjusted relative risk (RR) of 2.6 (95% CI, 1.3 to 5.3) excluding primary
      failures and 1.6 (95% CI, 1.0 to 2.7) when accounting for the lower risk of
      primary failure for grafts. Transposed brachiobasilic fistulas also required less
      intervention (0.7 vs. 2.4 per access-year, P < 0.01) and were less likely to
      become infected (0 vs. 13%, P < 0.05) than grafts. Mature brachiocephalic
      fistulas were less likely to fail (RR 0.3, 95% CI, 0.1 to 1.0) and showed a trend
      for less thrombosis (RR 0.3, 0.1 to 1.1) than mature brachiobasilic fistulas.
      There was no significant difference in cumulative patency (failure-free survival)
      among the three types of access if primary failure was included at the median
      follow-up of 594 days. Transposed brachiobasilic fistulas provided catheter-free
      access one month sooner than brachiocephalic fistulas and one month later than
      upper arm grafts. CONCLUSIONS: Transposed brachiobasilic fistulas provide
      cumulative patency equivalent to upper arm grafts and brachiocephalic fistulas.
      They are less likely to thrombose and become infected than upper arm grafts.
      Compared with brachiocephalic fistula, they are more likely to mature but are at
      increased risk of thrombosis after maturation. Transposed brachiobasilic fistulas
      should be considered before placing an upper arm graft for patients that cannot
      achieve a functional brachiocephalic fistula.

PMID- 11576370
TI  - Evaluation of renal Kt/V as a marker of renal function in predialysis patients.
AB  - BACKGROUND: The use of renal Kt/V (r-Kt/V) as an indicator for the need of
      dialysis initiation has been recommended in the NKF-DOQI guidelines. In analogy
      to clinical practice in peritoneal dialysis, a fall of r-Kt/V below a threshold
      of 2.0 per week may indicate inadequate renal toxin elimination. However, there
      are no studies linking r-Kt/V with other parameters of glomerular filtration rate
      (GFR) in predialysis patients, and the validity of r-Kt/V as parameter for timing
      of dialysis initiation is unknown. METHODS: Renal function was assessed
      repeatedly in 125 patients (N = 465 measurements). In predialysis patients (r
      Kt/V <2.5 per week) r-Kt/V was compared with creatinine [CCr], urea [CUr],
      averaged creatinine/urea clearance [CCr/Ur], Cockcroft-Gault formula [CCG], and
      MDRD prediction equation 6 (MDRD6-GFR). The diagnostic performance of r-Kt/V as a
      parameter for timing the initiation of dialysis was evaluated. RESULTS: Renal
      Kt/V <2.5 was prevalent in 24.9% of cases (N = 116, mean 1.92 +/- 0.34). In this
      group mean CCr was 13.8 +/- 4.9, mean CUr 6.7 +/- 1.3, and CCr/Ur 10.2 +/- 2.9
      mL/min/1.73 m2. There was no correlation of r-Kt/V with serum creatinine and
      MDRD6-GFR, but a significantly positive correlation with CCr/Ur (r2 = 0.3382, P <
      0.001). Sensitivity of r-Kt/V to detect CCr/Ur < 10.5 mL/min/1.73 m2, defined as
      the threshold for dialysis initiation, was 73.6% with a specificity of 91.9%.
      CONCLUSIONS: These results suggest that r-Kt/V is a parameter of acceptable
      specificity but poor sensitivity for the timing of dialysis initiation.
      Additional measures of renal function, such as the average of measured creatinine
      and urea clearance, also should be taken into consideration when deciding on the
      timing of dialysis initiation prior to the development of clinical signs of
      uremia and malnutrition.

PMID- 11576371
TI  - Late referral and modality choice in end-stage renal disease.
AB  - BACKGROUND: We sought to determine whether late versus early referral to a
      nephrologist in patients with chronic kidney disease influences the initial
      choice of hemodialysis (HD) versus peritoneal dialysis (PD) or the likelihood of
      switching treatment modalities in the first six months of therapy. METHODS: Using
      New Jersey Medicare/Medicaid claims, all patients who started RRT between January
      1991 and June 1996 and were diagnosed with renal disease more than one year prior
      to RRT were identified. In the resulting cohort of 3014 patients, 35% had their
      first nephrologist consultation < or =90 days prior to initiation of dialysis.
      RESULTS: After controlling for demographic characteristics, socioeconomic status
      and underlying renal disease, age, black race [Odds ratio (OR) = 0.56], race
      other than black or white (OR = 0.56), and socioeconomic status (OR = 0.68)
      influenced the choice of initial treatment modality, but timing of the referral
      did not. However, patients starting on PD who were referred late were 50% more
      likely to switch to HD than were patients who saw a nephrologist earlier
      [Hazard's ratio (HR) = 1.47]. In patients originally on HD, diabetic nephropathy
      (HR = 1.49) and black race (HR = 0.69) influenced the likelihood of switching to
      PD, but the timing of referral did not. CONCLUSIONS: These results refute earlier
      findings that late referral may limit access to PD. We found that modality choice
      depends on factors such as age, race, or socioeconomic status, rather than on
      than timing of nephrologist referral. Late referral does not influence the
      likelihood to switch modality in patients starting on HD, but does so in patients
      starting on PD.

PMID- 11576372
TI  - Short daily hemodialysis rapidly improves nutritional status in hemodialysis
      patients.
AB  - BACKGROUND: Malnutrition is a common problem in maintenance hemodialysis patients
      and is associated with increased mortality and morbidity. Interventions such as
      oral or intravenous nutritional supplements have often failed to improve
      nutritional status. We studied the effect of a daily dialysis program on
      nutritional parameters. METHODS: Eight patients treated with standard
      hemodialysis (SHD) 4 to 5 hours three times per week were converted to daily
      hemodialysis (DHD) 2 to 2.5 hours six times per week. Serum albumin, prealbumin,
      and total cholesterol were evaluated every three months. Anthropometry and
      dietary evaluation were performed every six months. RESULTS: Serum albumin rose
      from 39.0 +/- 2.6 to 42.0 +/- 3.1 and 43.0 +/- 2.6 g/L, prealbumin from 0.36 +/-
      0.04 to 0.41 +/- 0.05 and 0.42 +/- 0.1 g/L, total cholesterol from 1.7 +/- 0.4 to
      1.9 +/- 0.4 and 1.8 +/-0.3 g/L at baseline and at 6 and 12 months, respectively,
      after switching patients to DHD. Daily protein intake increased from 1.29 +/-
      0.20 g/kg/day to 1.48 +/- 0.60 and 1.90 +/- 0.70 (P < 0.05). These changes were
      accompanied by a dry body weight increase of 2.4 +/- 1.6 kg (P < 0.005) at month
      6 and 4.2 +/- 2.8 kg at one year (P < 0.05). Lean body mass increased from 47.7
      +/- 4.9 kg to 49.1 +/- 5.9 (P < 0.05) and 50.5 +/- 6.2 (P < 0.05). CONCLUSIONS:
      Daily hemodialysis appears to be a suitable method to improve nutritional status
      in maintenance dialysis patients.

PMID- 11576373
TI  - Serum cystatin C-immunoglobulin high-molecular-weight complexes in kidney and
      liver transplant patients.
AB  - BACKGROUND: It has been suggested recently that the glomerular filtration rate
      (GFR) in renal transplant patients is underestimated by serum cystatin C due to
      an impaired filtration of complexed cystatin C with immunoglobulins.
      Consequently, serum cystatin C may not be a reliable marker of GFR in these
      patients. Our study was designed to determine whether this supposition is
      correct. METHODS: In 87 serum samples from patients with various kidney diseases,
      182 samples from renal transplant patients, and 72 samples from liver transplant
      patients, the concentrations of cystatin C and creatinine were determined, as
      well as the residual concentration of cystatin C after precipitation of
      macromolecules with polyethylene glycol (PEG; 6000 molecular weight). RESULTS:
      The residual concentration of serum cystatin C after precipitation with PEG in
      all cases was much higher (70 to 100%) than that expected in the case of the
      existence of cystatin C-immunoglobulin complexes. In the kidney and liver
      transplant patients, there was no significant correlation between the residual
      concentration of cystatin C and the postoperative time (r = -0.098). CONCLUSIONS:
      The results suggest that in renal or liver transplant patients there is no
      formation of high molecular weight serum cystatin C-immunoglobulin complexes,
      regardless of the post-transplant period.

PMID- 11576374
TI  - The natural history of azathioprine compliance after renal transplantation.
AB  - BACKGROUND: Successful renal transplantation requires long-term adherence to
      complex medical regimens, yet knowledge of post-transplant medication compliance
      is still inadequate. METHODS: The natural history of medication compliance was
      quantitatively documented using electronic medicine bottle monitors. Azathioprine
      use was recorded with medication monitors beginning at hospital discharge in a
      prospective cohort of 180 renal transplant recipients. These patients and 87
      other eligible patients, declining study participation, were followed up to five
      years. Compliance rates were associated with discrete clinical outcomes: acute
      rejection, allograft loss, and death. RESULTS: During the first six months, only
      8% of all azathioprine doses were missed. However, individual compliance rates
      varied widely, ranging from 16 to 100%, and each month, on average, 18% of
      patients skipped medication for four or more days. Outcome events were not
      different between study participants and those refusing study. However, lower
      compliance rates during the first six months were associated in a "dose-response"
      fashion with acute rejection (P = 0.006) and allograft loss (P = 0.002).
      Declining compliance during the first 90 days was a strong risk factor both for
      later acute rejection (odds ratio = 13.9, 95% CI, 2.9 to 68, P = 0.001), and
      allograft loss (odds ratio = 4.3, 95% CI, 1.1 to 16, P = 0.032). CONCLUSIONS:
      Electronic monitoring provides a temporal description and quantitation of
      medication compliance. Reduced azathioprine compliance was highly associated with
      acute rejection and allograft loss. Trends in early compliance behavior predict
      later outcomes, thus providing unique opportunities for intervention.

PMID- 11576375
TI  - Filtration of native and glycated beta2-microglobulin by charged and neutral
      dialysis membranes.
AB  - BACKGROUND: It has been postulated that protein glycation and formation of
      advanced glycation end products (AGE) are among toxic factors in chronic uremia,
      whether the renal disease is of diabetic or nondiabetic origin. In this setting,
      AGE-modified beta2-microglobulin (beta2m) may favor dialysis beta2m-related
      dialysis amyloidosis. Consequently, efficient removal of modified beta2m by
      highly permeable dialysis membranes is as important as removal of native beta2m
      to postpone the development of dialysis amyloidosis. METHODS: To define the role
      of dialysis membrane surface electronegativity on plasma protein transfer, an in
      vitro model was used to test the interactions of native and glycated beta2m with
      various highly permeable dialysis membranes. An experimental circuit with
      minidialyzers was used. The neutral high-flux polysulfone membrane (PS), the
      electronegative polymethylmetacrylate membrane (PMMA), the electronegative AN69
      membrane and a modified AN69 membrane, the surface of which was neutralized with
      polyethyleneimine (AN69-PEI), were tested using both native beta2m and the more
      acidic glycated beta2m. Protein mass transfer and binding to the membrane were
      measured. RESULTS: Mass transfer of glycated beta2m was significantly decreased
      through all membranes tested when compared with native beta2m. This result was
      due to the increased molecular weight of beta2m, which became less permeable to
      porous membranes, whereas adsorption of both native and glycated beta2m to
      membranes, due to ionic interactions, decreased similarly with AN69 and AN69-PEI,
      but remained unchanged with PS and PMMA. Moreover, surface neutralization of AN69
      membrane did not alter its core binding capacity, since beta2m absorption
      accounted for 98 and 97% and glycated beta2m for 83.7 and 81.4% of the protein
      removed with AN69 and AN69-PEI, respectively. CONCLUSION: Clearance of glycated
      beta2m through highly permeable neutral and negatively charged membranes was
      lower than that of native beta2m, reflecting a decreased sieving coefficient for
      the neoformed higher molecular weight and conformationally altered molecule. The
      binding capacity of the neutral PS was roughly half that of the charged
      membranes. Neutralizing surface electronegativity of the AN69 membrane with PEI
      did not alter its binding capacity. These results suggest that it would be useful
      for dialysis protocols to include comparative studies of both serum native and
      modified beta2m in order to prevent beta2m-amyloidosis.

PMID- 11576376
TI  - Differential effects of growth hormone therapy in malnourished hemodialysis
      patients.
AB  - BACKGROUND: Malnutrition is common in chronic hemodialysis patients and is
      associated with increased morbidity and mortality. Several factors such as
      metabolic acidosis, hyperparathyroidism, and insulin as well as growth hormone
      (GH) resistance may lead to enhanced protein catabolism. Recombinant human growth
      hormone (rhGH) has been proposed as treatment of malnutrition because of its
      anabolic effects. METHODS: In the present placebo-controlled, double blind study,
      the effects of three months of rhGH therapy on nutritional and anthropometric
      parameters, on bone metabolism and bone mineral density (BMD), as well as on
      polymorphonuclear leukocyte (PMNL) function and quality of life (QoL) were
      evaluated in 19 malnourished hemodialysis patients (10 females and 9 males) with
      a mean age of 59.3 +/- 13.4 years. RhGH (0.125 IU/kg) was given three times a
      week during the first four weeks and 0.25 IU/kg thereafter three times a week
      after each dialysis session. RESULTS: Insulin-like growth factor I (IGF-I)
      concentration rose significantly from 169.2 +/- 95.6 ng/mL to 262.9 +/- 144.4
      ng/mL (p< 0.01) in the group receiving rhGH. Albumin, prealbumin, transferrin,
      cholesterol, high-density lipoprotein (HDL) cholesterol, cholinesterase,
      predialytic creatinine, and blood urea nitrogen showed no significant changes
      during the three months in both groups. Total body fat (%TBF) was slightly
      reduced after three months (P = NS) in the patients receiving GH, whereas lean
      body mass (LBM) remained stable during therapy. Procollagen I carboxy terminal
      peptide (PICP), a marker of bone formation, increased significantly after three
      months from 250.1 +/- 112.6 to 478.5 +/- 235.2 microg/L (P < 0.01) in the GH
      treated patients, whereas parameters of bone resorption like telopeptide ICTP
      showed only a slight increase (50.3 +/- 18.5 vs. 70.0 +/- 39.5 microg/L, P = NS).
      BMD at the lumbar spine decreased significantly after three months in the
      treatment group (0.8 +/- 0.17 vs. 0.77 +/- 0.16 g/cm2, P < 0.01), whereas BMD at
      the femoral neck remained stable in both groups. Phagocytic activity of PMNLs
      increased significantly after three months of therapy with rhGH, whereas other
      parameters of PMNL function were not affected by GH. QoL was slightly improved in
      the GH treated group, but decreased markedly in the placebo group. CONCLUSIONS:
      Three months of treatment with rhGH in malnourished patients on chronic
      hemodialysis causes a significant increase in IGF-I levels without significant
      changes in nutritional and anthropometric parameters. In contrast, bone turnover
      was enhanced with an initial decrease in BMD at the lumbar spine, and phagocytic
      activity of PMNLs was increased.

PMID- 11576377
TI  - Determinants of physical performance in ambulatory patients on hemodialysis.
AB  - BACKGROUND: Physical performance measures, particularly gait speed, have been
      useful as predictors of loss of independence, institutionalization, and mortality
      in older nonuremic individuals. Gait speed has not been evaluated as a predictor
      of these important outcomes in patients on hemodialysis, nor have the
      determinants of gait speed in the dialysis population been studied. METHODS: We
      performed a cross-sectional analysis to determine whether demographic, clinical,
      or nutritional status variables were related to physical performance in a group
      of 46 hemodialysis patients treated at three University of California San
      Francisco-affiliated dialysis units. Three physical performance measures were
      examined, including gait speed, time to climb stairs, and time to rise from a
      chair five times in succession. Forward stepwise linear-regression analysis was
      performed with each physical performance measure as the dependent variable and
      the following candidate predictor variables: age, gender, body mass index,
      dialysis vintage, Kt/V, albumin, blood urea nitrogen, creatinine, hematocrit,
      lean body mass, phase angle, ferritin, and the following comorbidities:
      hypertension, diabetes mellitus, coronary artery disease, peripheral vascular
      disease, and cerebrovascular disease. RESULTS: Subjects included 31 men and 15
      women aged 22 to 87 years (mean +/- SD, 52 +/- 17). The mean gait speed for the
      group was 113.1 +/- 34.5 cm/s (low compared with norms established for persons of
      similar age). Results of multivariable regression showed that age, albumin, and
      Kt/V were important determinants of gait speed in this population. Overall, the
      model explained 52% of the variability in gait speed (r = 0.72, P < 0.0001).
      Qualitatively similar results were obtained using stair-climbing time or chair
      rising time as the dependent variables, except that comorbidity was more
      important than age for stair climbing. The addition of physical activity level to
      the models did not eliminate the associations of albumin or Kt/V with physical
      performance. CONCLUSIONS: Physical performance is significantly impaired in
      ambulatory hemodialysis patients and is related to age, serum albumin, and
      dialysis dose. Prospective studies are needed to determine whether modification
      of dialysis dose or nutritional interventions can improve physical performance in
      patients on hemodialysis.

PMID- 11576378
TI  - Physiological aspects of pig-to-primate renal xenotransplantation.
AB  - BACKGROUND: Few data exist on the physiological aspects of pig-to-primate renal
      xenotransplantation. METHODS: Use of organs transgenic for human decay
      accelerating factor has allowed assessment of the metabolic and hormonal
      functions of these xenografts. RESULTS: Porcine renal xenografts largely maintain
      plasma electrolyte homeostasis. An increase in proteinuria was detected that may
      result from graft injury. In contrast to allotransplantation a severe anaemia
      developed requiring recipient treatment with exogenous human erythropoietin.
      CONCLUSIONS: Our experience provides qualified encouragement for the likely
      physiological compatibility of pig and primate species, but identifies areas
      where a xenograft may not match the performance of an allograft.

PMID- 11576379
TI  - Hemofiltration reduces the serum priming activity on neutrophil chemiluminescence
      in septic patients.
AB  - BACKGROUND: Priming of the polymorphonuclear neutrophil (PMN) response has been
      implicated in the activation of oxidative burst and tissue injury in patients
      with septic shock and acute renal failure (ARF). This study evaluated whether
      hemofiltration (HF) removes substances able to enhance the oxidative burst of
      PMNs. METHODS: Chemiluminescence (CL) priming activity induced by sera and
      ultrafiltrates of seven patients with septic shock, multiorgan dysfunction
      syndrome, and ARF (ARF/HF group) and of 10 uremic stable patients (Control/HF
      group) was evaluated on normal human PMNs stimulated with bacterial formyl
      methionyl-leucyl-phenylalanine (FMLP). Patients submitted to HF were studied by
      determining blood and ultrafiltrate interleukin-8 (IL-8), platelet-activating
      factor (PAF), and CL priming activity at the beginning (T0), and after four hours
      (T4) of treatment. RESULTS: Preincubation of normal human PMNs with sera and
      ultrafiltrates from septic patients induced a potent priming of CL activity in
      subsequent FMLP stimulation. In the ARF/HF group, the prefilter blood
      concentrations of IL-8 and CL PMN-priming activity significantly decreased during
      the four hours of HF treatment, with a loss of IL-8 in the ultrafiltrate of 6930
      (median, range 4292 to 9282) ng per four hours. PAF detected in the ultrafiltrate
      and associated with the membrane (7.3 ng, range 1.45 to 9.89) was minimal. In the
      ARF/HF group, a significantly positive correlation between CL PMN-priming
      activity and IL-8 concentrations was observed. The CL priming activity in blood
      and ultrafiltrates was reduced to 55 and 46% by preabsorption with monoclonal
      antibody (mAb) anti-IL-8. In contrast, the PAF receptor antagonist WEB 2170 did
      not affect CL priming activity. In the control/HF group, the CL PMN-priming
      activity was significantly lower than in the ARF/HF group and was independent of
      IL-8. CONCLUSIONS: Sera from septic patients demonstrate an enhanced CL priming
      activity on PMNs. This activity is reduced by ultrafiltration and is due, at
      least in part, to ultrafiltered IL-8.

PMID- 11576380
TI  - Nephritis promoted by oxidative injury.

PMID- 11576381
TI  - Escape from antidiuresis: a good story.

PMID- 11576382
TI  - Does choice of membrane or modality impact oxidant stress in hemodialysis
      therapy?

PMID- 11576383
TI  - Familial cases of Berger's disease and anaphylactoid purpura.

PMID- 11576384
TI  - Inhibition of renin secretion by angiotensin II receptor blockage?

PMID- 11576386
TI  - ANCA-associated renal vasculitis.

PMID- 11576388
TI  - Enteric nervous system disorders: genetic and molecular insights for the
      neurogastroenterologist.
AB  - The goals of this review are to summarize some of the novel observations on the
      genetic and molecular basis of enteric nervous system disorders, with particular
      emphasis on the relevance of these observations to the practicing
      neurogastroenterologist. In the last two decades, there has been a greater
      understanding of genetic loci involved in congenital forms of pseudo-obstruction
      and Hirschsprung's disease; and the contribution of endothelins and nuclear
      transcription factors to the development of the enteric nervous system. In
      addition, clarification of the molecules involved in the activation of the
      peristaltic reflex, the disorders of the interstitial cells of Cajal, the
      clinical manifestations of mitochondrial cytopathies affecting the gut, and the
      application of neurotrophic factors for disorders of colonic function have
      impacted on practical management of patients with gut dysmotility.

PMID- 11576389
TI  - Do gap junctions couple interstitial cells of Cajal pacing and neurotransmission
      to gastrointestinal smooth muscle?
AB  - Interstitial cells of Cajal (ICC) pace gastrointestinal phasic activity and
      transmit nerve activity. Gap junctions may couple these cells to smooth muscle,
      but no functional evidence exists. The objective of this study was to use
      uncouplers of gap junctions, 18 alpha-glycyrrhetenic acid and its water-soluble
      analogue carbenoxolone, to evaluate if gap junctions function in pacing and
      neurotransmission. After inhibition of nerve function with tetrodotoxin (TTX) and
      N(G)-nitro-L-arginine (L-NOARG), ionomycin- or carbachol-initiated regular phasic
      activities of circular muscle strips from canine colon and ileum. In some cases,
      the primary ICC network responsible for pacing was removed. The effects of
      inhibitors of gap junction conductance (10(-5)-10(-4) mol L(-1)) on frequencies
      and amplitudes of contraction were compared to appropriate time controls. Lower
      oesophageal sphincter (LOS) relaxations to nerve stimulation were studied before
      and after inhibition of gap junction functions. No major changes in LOS
      relaxations or frequencies of colonic or ileal contractions occurred, but
      amplitudes of contractions decreased from these agents. Similar results were
      obtained when the myenteric plexus-ICC network of ileum was removed. Regular
      phasic activity was not obtained after removal of the colon submuscular plexus
      ICC. These findings suggest that mechanisms other than gap junctions couple gut
      pacemaking activity and nerve transmission.

PMID- 11576390
TI  - Two-dimensional high-resolution motility mapping in the isolated feline duodenum:
      methodology and initial results.
AB  - Several types of electrical events occur in the small intestine but their spatial
      and temporal contributions to overall motility are not clear. In order to
      quantify local motility in greater detail, a new technique of recording and
      analysing movements at multiple sites was developed. Use was made of isolated
      segments of feline duodenum superfused in a tissue bath. Multiple marker dots (20
      75) were placed on the serosal surface by applying fine spots of candle soot in
      rectangular arrays (1-2 mm dot separation). A digital video camera was used to
      record spontaneous movements of the dots for periods of 10-30 min. After each
      experiment, 4-6 periods (10-60 s each) of video frames were transferred to a
      computer (25 fps, 720 x 576 pixels) and the movements of the dots was tracked
      every 40 ms using custom-made software. Initial results (eight experiments) show
      that spontaneous motility is remarkably variable, both in space and time. Three
      types of movement could be discerned: (i) periodic, rolling or pendular
      movements, with a frequency of approximately 15 min-1 occurring predominantly in
      the longitudinal direction; (ii) twitches, wherein a subset of dots were suddenly
      displaced longitudinally; and (iii) drifts of most of the dots in a circular or
      oblique direction. All three types of movement occurred throughout every
      recording session although their relative magnitudes differed greatly from moment
      to moment. Occasionally, it was possible to detect propagated 'contractions' with
      an apparent velocity of 10 mm s(-1). Immobilizing the preparation at one point by
      inserting a needle through the middle of the array of markers had a negligible
      effect on the displacements, whereas application of verapamil (10(-5) mol L(-1))
      reduced or abolished motility. In summary, we present a new technique to map in
      detail two-dimensional motility at the surface of the intestine. Initial results
      seem to suggest that motility at the serosal surface is not uniform and highly
      anisotropic.

PMID- 11576391
TI  - Effect of sildenafil, a phosphodiesterase-5 inhibitor, on oesophageal peristalsis
      and lower oesophageal sphincter function in cats.
AB  - The propagation of oesophageal peristaltic contractions and lower oesophageal
      sphincter (LOS) relaxation depends on neural release of nitric oxide (NO) which
      acts to increase intracellular cGMP. Sildenafil, a phosphodiesterase-5 inhibitor
      that increases cGMP, reduces basal LOS pressure in patients with achalasia. We
      investigated the effect of sildenafil on the propagation of oesophageal
      contractions and LOS relaxation in the cat. Oesophageal manometry was performed
      in five cats under light sedation. Peristaltic contractions were monitored at 1,
      2, 3, 4 and 8 cm proximal to the LOS, at the LOS using a Dent sleeve, and at 3 cm
      distal to the upper oesophageal sphincter. Swallow-induced oesophageal
      contractions and LOS relaxation were recorded during 30 min before and 30 min
      after intravenous administration of sildenafil. Sildenafil reduced the amplitude
      of oesophageal contractions only in the smooth muscle oesophagus. The latency
      from swallow to distal oesophageal contractions was significantly delayed. LOS
      pressure was significantly reduced but the relaxation nadir was not modified by
      sildenafil. Sildenafil has profound effects on oesophageal motility: it modifies
      propagation and amplitude of oesophageal contractions and reduces LOS pressure.
      Slowing down the propagation of contractions in the transitional zone between the
      striated and smooth muscle can be a useful tool in patients with segmental
      aperistalsis or intermittent simultaneous contractions, while the effect on the
      LOS can benefit patients with achalasia.

PMID- 11576392
TI  - Colonic mechanoreceptor inputs to rat lumbo-sacral dorsal horn neurones:
      distribution, thresholds and chemosensory modulation.
AB  - In order to better understand the central processing of visceral sensory
      information, we studied the responses of lumbo-sacral dorsal horn (L4-S1)
      neurones to colonic stimuli in anaesthetized rats. Twenty-four neurones responded
      to distal colonic distension with a 2.5-cm balloon; six of these were tested with
      proximal colonic distension, to which none responded. All neurones tested
      responded to somatic non-noxious inputs (tail movement). Responses to colonic
      distension were excitatory (n=22) or inhibitory (n=2). Sixteen neurones responded
      at a threshold of 20 mmHg or less, five at 20-40 mmHg, and three at 40-80 mmHg.
      Three of 10 neurones tested showed increased responses to colonic distension
      after intraluminal perfusion with bile. Bile itself did not evoke a response. We
      conclude that lumbo-sacral spinal neurones selectively receive mechanosensory
      inputs from the distal colon. Neurones respond at thresholds within and above the
      physiological range. Dorsal horn neurones receiving colonic mechanosensory inputs
      are not directly modulated by chemosensory inputs, but their responsiveness to
      distension may be augmented.

PMID- 11576393
TI  - Effect of 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced ileitis on the motor
      function of non-inflamed rat gastric fundus.
AB  - During intestinal inflammation, motility disturbances are not restricted to
      inflamed regions, but may also occur in remote non-inflamed sites of the
      gastrointestinal tract. Our aim was to investigate the motor function of the
      gastric fundus after the induction of terminal ileitis in the rat. Ileal
      inflammation was induced by intraluminal installation of 2,4,6
      trinitrobenzenesulphonic acid (TNBS) into the ileum. Inflammation was assessed
      both histologically and biochemically. Contractions and relaxations of
      longitudinal muscle strips from the gastric fundus were studied 36 h and 1 week
      later. During the acute phase of ileal inflammation (36 h), the non-inflamed
      stomach was distended. The contractility of longitudinal muscle strips of the
      gastric fundus was decreased due to a post-receptor defect. In addition,
      nonadrenergic noncholinergic (NANC) relaxations were inhibited due to neuronal
      dysfunction. Aortic contractility remained normal and the mere presence of food
      in the stomach did not account for the disturbed neuromuscular function in the
      gastric fundus. Ablation of extrinsic primary afferent neurones by capsaicin
      further impaired gastric fundus contractility. Transection and re-anastomosis of
      the jejunum reversed the effect of TNBS-induced ileitis on the neuromuscular
      function of the gastric fundus. One week after TNBS, cholinergic
      neurotransmission was increased in the gastric fundus. During acute ileitis,
      smooth muscle cell contractility and inhibitory NANC neurotransmission are
      inhibited in the non-inflamed gastric fundus. This phenomenon may be mediated by
      intrinsic connections within the enteric nervous system.

PMID- 11576394
TI  - Effect of calcitonin gene-related peptide (CGRP) on motility and on the release
      of substance P, neurokinin A, somatostatin and gastrin in the isolated perfused
      porcine antrum.
AB  - We studied the effect of porcine CGRP (pCGRP) in concentrations from 10(-10) to
      10(-8) mol L(-1) on the motility and on the release of substance P, neurokinin A,
      somatostatin and gastrin in the antrum using the isolated perfused porcine antrum
      as experimental model. In addition, we studied the localization of CGRP by
      immunohistochemistry in the porcine antrum. CGRP-immunoreactive nerve fibres were
      found mainly in the submucous layer and in the external muscle coat, where they
      were seen in all layers, and in the ganglia of the myenteric nervous plexus. The
      frequency of contraction was significantly and dose-dependently increased from a
      basal level of 11.8 +/- 0.5 contractions per 5 min to 24.4 +/- 3.6 contractions
      per 5 min at pCGRP 10(-8) mol L(-1). At this dose, the release of substance P and
      neurokinin A was significantly increased to 470 +/- 149% and 217 +/- 26%,
      respectively, compared to basal release. The effect of pCGRP was unaffected by
      the addition of the nonpeptide antagonists for the NK-1 (CP-99994) and NK-2
      receptors (SR48968), both at 10(-6) mol L(-1), whereas atropine (10(-6) mol L(
      1)) completely abolished the motor effect of pCGRP. The release of somatostatin
      was significantly increased by 154 +/- 15% in response to CGRP at 10(-8) mol L(
      1). The release of gastrin was unaffected by pCGRP. In conclusion, pCGRP
      increases contractile activity in the porcine antrum, an effect that involves
      cholinergic mechanisms but is independent of the release of substance P and
      neurokinin A. in addition, pCGRP increases the release of somatostatin but has no
      effect on gastrin release in the isolated perfused porcine antrum.

PMID- 11576395
TI  - Manometric abnormalities of the oesophagus in patients with Parkinson's disease.
AB  - Dysphagia in Parkinson's disease (PD) is known to correlate with abnormalities of
      oropharyngeal function. Oesophageal abnormalities have not been previously
      demonstrated to correlate with dysphagia. The aim of the study was to determine
      if motor dysfunction of the oesophageal body correlates with dysphagia or disease
      severity in PD. Twenty-two patients with PD were assessed for the severity of
      their dysphagia (scale of 1-7) and severity of PD (Hoehn and Yahr scale 1-4). All
      underwent oesophageal manometry. Dysphagia was present daily in 10 patients
      (45%). Parkinson's disease was graded as severe (Hoehn and Yahr > or =3) in eight
      (36%) patients. Oesophageal manometry was abnormal in 16 (73%) patients. Thirteen
      patients had either complete aperistalsis or multiple simultaneous contractions
      (diffuse oesophageal spasm). These findings were significantly more common in
      patients with daily dysphagia (90% vs. 33%; P < 0.005), and were not related to
      duration or severity of PD. We conclude that the presence of aperistalsis or
      multiple simultaneous contractions in the oesophagus does correlate with
      dysphagia and is independent of PD severity or duration. This may reflect
      selective involvement of either the dorsal motor nucleus of the vagus or the
      oesophageal myenteric plexus.

PMID- 11576396
TI  - ATP-gated ion channel P2X(3) is increased in human inflammatory bowel disease.
AB  - P2X(3) is a novel ATP-gated cation channel that is selectively expressed by small
      diameter sensory neurones in rodents, and may play a role in nociception by
      binding ATP released from damaged or inflamed tissues. We have studied, for the
      first time, P2X(3) immunoreactivity in human inflammatory bowel disease, using
      Western blotting and immunohistochemistry. A major 66-kDa specific protein was
      found by Western blotting in all colon extracts. In the inflamed group there was
      a significant two-fold increase in the relative optical density of the 66-kDa
      band (21.2 +/- 3.1; n=8) compared to controls (11.4 +/- 3.7; n=8; P=0.009). In
      the control colon, P2X(3)-immunoreactive neurones were scattered throughout the
      myenteric and submucosal plexuses, with some neurones showing immunopositive
      axons/dendrites. The pattern of immunostaining was similar to the neuronal marker
      peripherin. In general, the intensity of the staining was greater in myenteric
      than submucosal neurones. The number of P2X(3)-immunoreactive neurones was
      significantly increased in the myenteric plexus of inflamed colon compared to
      controls (n=13; P=0.01). In humans, unlike rodents, P2X(3) is thus not restricted
      to sensory neurones. Increased P2X(3) in inflamed intestine suggests a potential
      role in dysmotility and pain, for which it represents a new therapeutic target.

PMID- 11576397
TI  - Familial cutaneous mastocytosis.
AB  - Cutaneous mastocytosis appears to occur sporadically; however, familial
      inheritance has been reported in 50 families since the mid-1880s. We report four
      cases of telangiectasia macularis eruptiva perstans (TMEP) occurring in three
      generations of a family. Whereas most patients with TMEP manifest in adulthood,
      all of the members of this family developed initial lesions during childhood.
      This is the third documented instance of familial mastocytosis affecting members
      of three generations, and the first report of familial TMEP. Although the
      inheritance pattern is unknown, the presentation of disease in this family
      further supports the hypothesis of an autosomal dominant mode of transmission
      with incomplete penetrance.

PMID- 11576398
TI  - The use of digital dermoscopy for the follow-up of congenital nevi: a pilot
      study.
AB  - One of the main problems in the management of congenital nevi is the potential
      risk for malignant transformation and the resulting need for follow-up
      examination. Dermoscopy is a noninvasive technique that has been shown to be
      useful for the follow-up of benign melanocytic skin lesions as well as the early
      diagnosis of malignant melanoma. Therefore we thought to use the digital
      dermoscopy (DD) technique for the follow-up of congenital nevi. For documentation
      purposes we registered an overview, and the following standardized dermoscopic
      images of every lesion: representative architectural pattern, border of the
      lesion, and regions of "special interest." In all instances the examination with
      digital dermoscopy was well tolerated by the patients and the integration of the
      parents to the "live" examination on the computer screen was appreciated. The
      follow-up was easy to perform with these standardized documents. We showed the
      feasibility of follow-up of congenital nevi using digital dermoscopy.
      Furthermore, we identified three different patterns as well as some typical
      structures seen in congenital nevi by DD.

PMID- 11576399
TI  - Effects of breathable disposable diapers: reduced prevalence of Candida and
      common diaper dermatitis.
AB  - Infants wearing breathable disposable diapers experienced significantly less
      diaper dermatitis (DD) compared to infants wearing standard, nonbreathable
      disposable diapers in a series of double-blind clinical trials. Severe DD,
      including confirmed infection with Candida albicans, was reduced by 38-50% among
      infants wearing highly breathable (HB) diapers. The prevalence of DD was
      inversely related to the breathability of the garments. The inhibitory effect of
      breathable diapers on the survival of Candida was further confirmed in controlled
      experiments with adult volunteers. A suspension of C. albicans cells was applied
      to delineated sites on the volar forearm. Each site was then covered by a full
      thickness patch from either an HB or a standard diaper. Survival of Candida
      colonies was reduced by almost two-thirds in the breathable diaper-covered sites
      compared to the control sites.

PMID- 11576400
TI  - Occurrence of supernumerary nipples in children with kidney and urinary tract
      malformations.
AB  - The reported data on the association of kidney and urinary tract malformations
      with supernumerary nipples are contradictory. We examined 200 children, ages 1
      month-16 years, who were being followed because of recurrent urinary tract
      infection for supernumerary nipples. The patients were divided into two groups:
      those who were found to have urinary tract malformations on radiographic studies
      (n=92) and those who were not (n=108). All children were examined for any
      abnormal pigmentation along the milk line, and the entire body was examined for
      ectopic supernumerary nipples. Two of the children with proved urinary tract
      pathology and two of the children with no urinary tract pathology had
      supernumerary nipples. The odds ratio for having supernumerary nipples among the
      first group was 1.18 (95% CI: 0.084-16.53, p=0.627). Our results indicate no
      association between kidney and urinary tract malformations and supernumerary
      nipples. We believe the message to the practicing physician is that there is no
      need for radiographic or ultrasonographic investigation of the urinary tract in
      asymptomatic children found to have supernumerary nipples on routine physical
      examination.

PMID- 11576401
TI  - Minocycline hypersensitivity syndrome with hypotension mimicking septic shock.
AB  - Minocycline is a semisynthetic tetracycline derivative that is often used in the
      treatment of acne vulgaris. A serious but rare adverse effect caused by
      minocycline therapy is a hypersensitivity syndrome (HS), consisting of fever,
      skin eruption, and internal organ involvement that begins within 8 weeks of
      therapy initiation. We report a case of minocycline HS with unique features,
      namely, associated hypotension, and a rebound of the cutaneous eruption upon
      discontinuation of systemic steroids.

PMID- 11576402
TI  - Pigmented purpuric eruptions of childhood: a series of cases and review of
      literature.
AB  - Pigmented purpuric eruptions comprise a group of benign dermatoses that are
      characterized clinically by pinpoint petechiae and purpura on a hyperpigmented
      base and histologically by capillaritis. The etiology of this group of disorders
      is unknown, although aberrant cell-mediated immunity has been proposed. Pigmented
      purpuric eruptions are well characterized in the pediatric population. In this
      case series we present three children with these disorders and review the
      clinical subtypes of pigmented purpuric eruptions that have been described in the
      literature.

PMID- 11576403
TI  - Self-healing generalized infantile myofibromatosis with elevated urinary bFGF.
AB  - We report a case of generalized infantile myofibromatosis with favorable outcome
      despite systemic involvement. Elevated urinary bFGF levels during the active
      phase of the disease suggested an angiogenic stimulation in the pathogenesis of
      myofibromatosis.

PMID- 11576404
TI  - Pyoderma gangrenosum in two siblings: a familial predisposition.
AB  - We report pyoderma gangrenosum in two siblings with onset during childhood and no
      associated systemic abnormalities. The patients were born of nonconsanguineous,
      healthy parents. Treatment with oral corticosteroids produced an excellent
      clinical response, followed by recurrence after cessation of therapy. Steroids
      were restarted in combination with dapsone to prevent further recurrence.

PMID- 11576405
TI  - Urticaria pigmentosa associated with Wilms tumor.
AB  - Urticaria pigmentosa is the most common manifestation of mastocytosis, with the
      majority of cases undergoing spontaneous resolution, especially in children.
      Several reports have documented hematologic malignancies developing in patients
      with urticaria pigmentosa. We present a 4.5-year-old boy with urticaria
      pigmentosa who developed Wilms tumor. To our knowledge, coexisting urticaria
      pigmentosa and Wilms tumor have not previously been described.

PMID- 11576407
TI  - Giant congenital nevus with progressive sclerodermoid reaction in a newborn.
AB  - Giant congenital melanocytic nevi are a rare occurrence in the pediatric
      population. The risk of malignant transformation associated with these lesions
      has been well established; however, the management strategies for giant
      congenital nevi remain controversial. We report an unusual sclerodermoid reaction
      in a giant congenital nevus in a 6-week-old Caucasian girl. Given its abnormal
      clinical appearance, the entire lesion was excised. The histology was consistent
      with an atypical compound/sclerosing spindle and epithelioid cell congenital
      nevus. No evidence of malignant change was seen histologically. The incidence of
      malignant transformation in giant congenital nevi has been difficult to
      calculate. Review of the literature yields an incidence of between 4 and 9%,
      favoring surgical excision of these lesions where possible. Atypical
      presentations of giant congenital nevi are rare, and we have found no other
      reported cases with a stromal change similar to that seen in our patient. We
      hypothesize that this change may represent an atypical host reaction to the nevus
      cells.

PMID- 11576406
TI  - Necrobiosis lipoidica in a 9-year-old girl with new-onset type II diabetes
      mellitus.
AB  - Necrobiosis lipoidica (NL) is an idiopathic dermatologic condition that is
      strongly associated with, but not pathognomonic for, diabetes mellitus. It is
      more commonly seen in women than men and in adults than children. We present the
      youngest child, to our knowledge, diagnosed with NL at initial presentation with
      type II diabetes mellitus. We review the literature and discuss pathogenesis,
      clinical features, and treatment options for NL.

PMID- 11576408
TI  - Pseudo-Kaposi sarcoma with arteriovenous malformation.
AB  - Pseudo-Kaposi sarcoma with vascular malformation (Stewart-Bluefarb syndrome) is
      an uncommon and important entity characterized by congenital arteriovenous
      malformation and skin lesions that may resemble Kaposi sarcoma. This is usually
      seen in the lower limb of young people. We report a case of this syndrome in a 17
      year-old boy who had skin lesions on the right leg and foot.

PMID- 11576409
TI  - Scrofuloderma with multiple organ involvement in a 5-year-old child.
AB  - Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis seen in
      children in developing countries. We report a 5-year-old child with cutaneous
      tuberculosis with involvement of lymph nodes, lungs, and the musculoskeletal and
      central nervous systems, which was not clinically obvious. Antituberculous
      treatment led to marked clinical improvement. The importance of a thorough search
      for internal organ involvement in patients presenting with cutaneous tuberculosis
      is emphasized.

PMID- 11576410
TI  - Cranioectodermal dysplasia: a new patient with an inapparent, subtle phenotype.
AB  - Cranioectodermal dysplasia is a rare syndrome characterized by craniofacial and
      skeletal anomalies and ectodermal dysplasia. Life-threatening associated
      conditions (i.e., kidney failure and abnormal regulation of the parathyroid-bone
      axis) can also develop. We report a patient whose features are suggestive of an
      inapparent, subtle phenotype of the syndrome. The patient is a 4-year-old girl
      with only dolichocephaly and clinodactyly; microdontia, hypodontia, and
      taurodontia (i.e., cone-shaped teeth); anteverted nares, full cheeks, and everted
      lower lip; epicanthal folds, hypertelorism and hyperopia; and corpus callosum
      hypoplasia. She has no rhizomelic limb shortening or hair abnormalities. In view
      of the rarity of the cranioectodermal dysplasias, the variability of the
      phenotype, and the uncertain outcome of some previously described patients, we
      believe this inapparent, subtle case should reported to enable better
      understanding and treatment of this rare syndrome.

PMID- 11576411
TI  - Vegetant bromoderma in an Infant.
AB  - Bromoderma is a cutaneous reaction caused by the use of products containing
      bromide. In this report we describe a 2-month-old girl who was admitted to our
      institution with vegetative lesions on the face and scalp owing to the
      administration of a syrup containing sodium bromide.

PMID- 11576412
TI  - Doubled dose of oral terbinafine is required for Microsporum canis tinea capitis.
AB  - Fourteen children, ages 1-15 years, with Microsporum canis tinea capitis were
      given oral terbinafine for 4 weeks at the recommended daily dose according to
      their weight: 10-20 kg, 62.5 mg; 20-40 kg, 125 mg; > 40 kg, 250 mg. Because none
      of the patients had clinically responded to treatment by week 4 the dose of
      terbinafine was doubled (up to 250 mg) for an additional 4-8 weeks in six
      patients, and continued at the original dose in six patients. Two patients
      dropped out of the study. On final evaluation, four patients were cured after 8
      12 weeks of treatment. All cured patients received the doubled dose of
      terbinafine, except for one who was on the usual adult dose of 250 mg from the
      onset. Oral terbinafine was well tolerated by all but one patient, who
      experienced gastrointestinal disturbance and slightly raised transaminase levels
      during the first 4 weeks of treatment. Terbinafine side effects were not
      correlated with dosage or duration of treatment. We conclude that oral
      terbinafine should be dosed for M. canis tinea capitis at a revised schedule
      according to body weight: 10-25 kg, 125 mg/day and > 25 kg, 250 mg/day. The
      appropriate duration of terbinafine treatment remains to be determined.

PMID- 11576413
TI  - The effectiveness of wet wrap dressings using 0.1% mometasone furoate and 0.005%
      fluticasone proprionate ointments in the treatment of moderate to severe atopic
      dermatitis in children.
AB  - Various types of dressings have been used successfully in the treatment of atopic
      dermatitis. In this study we looked at the efficacy of two of the newer topical
      steroids when applied under wet wrap dressings for the treatment of refractory
      atopic dermatitis in children. Forty children with moderate to severe disease
      were randomized to receive either one-tenth-strength diluted 0.1% mometasone
      furoate ointment or one-tenth-strength diluted 0.005% fluticasone proprionate
      ointment. These were applied once a day over a 4-week period without wet wraps,
      or for 2 weeks without wet wraps followed by 2 weeks of application under wet
      wraps. There was a 2-week period for all patients when the topical treatment was
      standardized. At weekly follow-ups, patients were assessed by a single, blinded
      observer and objectively scored for disease extent and severity. A subjective
      score was also given for the impact of eczema on daily living. There was
      significant improvement in the disease severity from baseline during the first 2
      weeks of the open application arm (p=0.043), however, additional beneficial
      effects were limited after week 2. Wet wraps further improved the disease
      severity and extent after week 2 (p < 0.05), and were well tolerated. We
      concluded that both 0.1% mometasone furoate and 0.005% fluticasone proprionate
      ointments are effective in the treatment of atopic dermatitis, and that wet wraps
      are useful in further improving refractory disease in children.

PMID- 11576414
TI  - Cimetidine and levamisole versus cimetidine alone for recalcitrant warts in
      children.
AB  - Various immunomodulating agents have been used in the treatment of recalcitrant
      warts, but none is uniformly effective. Aggressive surgical therapy of warts in
      children is painful and may require general anesthesia. Drugs such as cimetidine
      and levamisole have been tried with varying success rates. Given the different
      target of activities of immunomodulation by cimetidine and levamisole, we
      questioned whether the combination might be more effective and conducted a double
      blind comparative trial of a combination of cimetidine and levamisole versus
      cimetidine alone. Forty-four patients with multiple recalcitrant warts were
      assigned to one of two treatment groups (groups A and B) in double-blind fashion.
      Of the 44 patients, 19 in group A and 20 in group B could be evaluated. At the
      end of therapy, cure rates (complete clearance) obtained were 31.5% of those in
      group A and 65% of those in group B (combination treatment). A statistically
      significant improvement was seen in patients treated with the combination of
      levamisole and cimetidine (p=0.0150). The rate of regression was faster in group
      B (average regression period of 7.8 weeks compared with 11 weeks in group A). The
      present study demonstrated that the combination of cimetidine with levamisole is
      more effective than cimetidine alone and is a highly effective therapy for the
      treatment of recalcitrant warts.

PMID- 11576415
TI  - What syndrome is this? Chronic mucocutaneous candidiasis.

PMID- 11576416
TI  - Solitary, lobulated, firm nodule.

PMID- 11576417
TI  - Vernix caseosa: a "natural biofilm" in very low birthweight infants.

PMID- 11576419
TI  - Macrodactyly in tuberous sclerosis.

PMID- 11576420
TI  - Congenital cutis laxa (dermatochalasia) with cardiac valvular disease.

PMID- 11576421
TI  - Disseminated and cutaneous aspergillosis in a premature infant: a fatal
      nosocomial infection.

PMID- 11576422
TI  - Localization and targeting of the VP14 epoxy-carotenoid dioxygenase to
      chloroplast membranes.
AB  - Abscisic acid (ABA) is a key regulator of seed dormancy and plant responses to
      environmental challenges. ABA is synthesized via an oxidative cleavage of 9-cis
      epoxy-carotenoids, the first committed and key regulatory step in the ABA
      biosynthetic pathway. Vp14 of maize encodes an epoxy-carotenoid dioxygenase that
      is soluble when expressed in E. coli. An important goal has been to determine how
      the soluble VP14 protein is targeted to epoxy-carotenoid substrates that are
      located in the thylakoid and envelope membranes of chloroplasts and other
      plastids. Using an in vitro chloroplast import assay, we have shown that VP14 is
      imported into chloroplasts with cleavage of a short stroma-targeting domain. The
      mature VP14 exists in two forms, one which is soluble in stroma and the other
      bound to thylakoid membranes. Analysis of a series of truncated VP14 mutants
      mapped the membrane targeting signal to the 160 amino acid N-terminal sequence. A
      putative amphipathic alpha-helix within this region is essential, but not
      sufficient, for the membrane targeting. Either deletion of or insertion of helix
      breaking residues into this region abolished the membrane binding, whereas a
      chimeric protein carrying just the amphipathic region fused with bacterial
      glutathione S-transferase failed to associate with the thylakoid membrane. The
      membrane-bound VP14 was partially resistant to chaotropic washes such as 0.1 M
      Na2CO3 (pH 11.5) and 6 M urea. Unlabelled recombinant VP14 inhibited the tight
      binding of imported VP14, suggesting that VP14 is associated with specific
      components of the thylakoid membrane.

PMID- 11576423
TI  - Phage display selection of hairpin loop soyacystatin variants that mediate high
      affinity inhibition of a cysteine proteinase.
AB  - Two hairpin-loop domains in cystatin family proteinase inhibitors form an
      interface surface region that slots into the active site cleft of papain-like
      cysteine proteinases, and determine binding affinity. The slot region surface
      architecture of the soybean cysteine proteinase inhibitor (soyacystatin N, scN)
      was engineered using techniques of in vitro molecular evolution to define
      residues that facilitate interaction with the proteinase cleft and modulate
      inhibitor affinity and function. Combinatorial phage display libraries of scN
      variants that contain mutations in the essential motifs of the first (QVVAG) and
      second (EW) hairpin-loop regions were constructed. Approximately 1010-1011 phages
      expressing recombinant scN proteins were subjected to biopanning selection based
      on binding affinity to immobilized papain. The QVVAG motif in the first hairpin
      loop was invariant in all functional scN proteins. All selected variants (30) had
      W79 in the second hairpin-loop motif, but there was diversity for hydrophobic and
      basic amino acids in residue 78. Kinetic analysis of isolated scN variants
      identified a novel scN isoform scN(LW) with higher papain affinity than the wild
      type molecule. The variant contained an E78L substitution and had a twofold lower
      Ki (2.1 pM) than parental scN, due to its increased association rate constant
      (2.6 +/- 0.09 x 107 M-1sec-1). These results define residues in the first and
      second hairpin-loop regions which are essential for optimal interaction between
      phytocystatins and papain, a prototypical cysteine proteinase. Furthermore, the
      isolated variants are a biochemical platform for further integration of mutations
      to optimize cystatin affinity for specific biological targets.

PMID- 11576424
TI  - The ubiquitin-specific protease UBP14 is essential for early embryo development
      in Arabidopsis thaliana.
AB  - The ubiquitin/26S proteasome pathway is a major route for selectively degrading
      cytoplasmic and nuclear proteins in eukaryotes. In this pathway, chains of
      ubiquitins become attached to short-lived proteins, signalling recognition and
      breakdown of the modified protein by the 26S proteasome. During or following
      target degradation, the attached multi-ubiquitin chains are released and
      subsequently disassembled by ubiquitin-specific proteases (UBPs) to regenerate
      free ubiquitin monomers for re-use. Here, we describe Arabidopsis thaliana UBP14
      that may participate in this recycling process. Its amino acid sequence is most
      similar to yeast UBP14 and its orthologues, human IsoT1-3 and Dictyostelium UbpA,
      and it can functionally replace yeast UBP14 in a ubp14Delta mutant. Like its
      orthologues, AtUBP14 can disassemble multi-ubiquitin chains linked internally via
      epsilon-amino isopeptide bonds using Lys48 and can process some, but not all,
      translational fusions of ubiquitin linked via alpha-amino peptide bonds. However,
      unlike its yeast and Dictyostelium orthologues, AtUBP14 is essential in
      Arabidopsis. T-DNA insertion mutations in the single gene that encodes AtUBP14
      cause an embryonic lethal phenotype, with the homozygous embryos arresting at the
      globular stage. The arrested seeds have substantially increased levels of multi
      ubiquitin chains, indicative of a defect in ubiquitin recycling. Taken together,
      the data demonstrate an essential role for the ubiquitin/26S proteasome pathway
      in general and for AtUBP14 in particular during early plant development.

PMID- 11576425
TI  - At-HSP17.6A, encoding a small heat-shock protein in Arabidopsis, can enhance
      osmotolerance upon overexpression.
AB  - Owing to their sessile lifestyle, it is crucial for plants to acquire stress
      tolerance. The function of heat-shock proteins, including small heat-shock
      proteins (smHSPs), in stress tolerance is not fully explored. To gain further
      knowledge about the smHSPs, the gene that encoded the cytosolic class II smHSP in
      Arabidopsis thaliana (At-HSP17.6A) was characterized. The At-HSP17.6A expression
      was induced by heat and osmotic stress, as well as during seed development.
      Accumulation of At-HSP17.6A proteins could be detected with heat and at a late
      stage of seed development, but not with osmotic stress, suggesting stress-induced
      post-transcriptional regulation of At-HSP17.6A expression. Overproduction of At
      HSP17.6A could increase salt and drought tolerance in Arabidopsis. The chaperone
      activity of At-HSP17.6A was demonstrated in vitro.

PMID- 11576426
TI  - The tomato Rme1 locus is required for Mi-1-mediated resistance to root-knot
      nematodes and the potato aphid.
AB  - The tomato Mi-1 gene confers resistance against root-knot nematodes (Meloidogyne
      spp.) and a biotype of the potato aphid (Macrosiphum euphorbiae). Four
      mutagenized Mi-1/Mi-1 tomato populations were generated and screened for altered
      root-knot nematode resistance. Four independent mutants belonging to two
      phenotypic classes were isolated. One mutant was chosen for further analyzes;
      rme1 (for resistance to Meloidogyne) exhibited levels of infection comparable
      with those found on susceptible controls. Molecular and genetic data confirmed
      that rme1 has a single recessive mutation in a locus different from Mi-1. Cross
      sections through galls formed by feeding nematodes on rme1 roots were identical
      to sections from galls of susceptible tomato roots. In addition to nematode
      susceptibility, infestation of rme1 plants with the potato aphid showed that this
      mutation also abolished aphid resistance. To determine whether Rme1 functions in
      a general disease-resistance pathway, the response against Fusarium oxysporum
      f.sp. lycopersici race 2, mediated by the I-2 resistance gene, was studied. Both
      rme1 and the wild type plants were equally resistant to the fungal pathogen.
      These results indicate that Rme1 does not play a general role in disease
      resistance but may be specific for Mi-1-mediated resistance.

PMID- 11576427
TI  - Mutagenesis and computer modelling approach to study determinants for recognition
      of signal peptides by the mitochondrial processing peptidase.
AB  - Determinants for the recognition of a mitochondrial presequence by the
      mitochondrial processing peptidase (MPP) have been investigated using mutagenesis
      and bioinformatics approaches. All plant mitochondrial presequences with a
      cleavage site that was confirmed by experimental studies can be grouped into
      three classes. Two major classes contain an arginine residue at position -2 or 
      3, and the third class does not have any conserved arginines. Sequence logos
      revealed loosely conserved cleavage motifs for the first two classes but no
      significant amino acid conservation for the third class. Investigation of
      processing determinants for a class III precursor, Nicotiana plumbaginifolia
      F1beta precursor of ATP synthase (pF1beta), was performed using a series of
      pF1beta presequence mutants and mutant presequence peptides derived from the C
      terminal portion of the presequence. Replacement of -2 Gln by Arg inhibited
      processing, whereas replacement of either the most proximally located -5 Arg or 
      15 Arg by Leu had only a low inhibitory effect. The C-terminal portion of the
      pF1beta presequence forms a helix-turn-helix structure. Mutations disturbing or
      prolonging the helical element upstream of the cleavage site inhibited processing
      significantly. Structural models of potato MPP and the C-terminal pF1beta
      presequence peptide were built by homology modelling and empirical conformational
      energy search methods, respectively. Molecular docking of the pF1beta presequence
      peptide to the MPP model suggested binding of the peptide to the negatively
      charged binding cleft formed by the alpha-MPP and beta-MPP subunits in close
      proximity to the H111XXE114H115X(116-190)E191 proteolytic active site on beta
      MPP. Our results show for the first time that the amino acid at the -2 position,
      even if not an arginine, as well as structural properties of the C-terminal
      portion of the presequence are important determinants for the processing of a
      class III precursor by MPP.

PMID- 11576428
TI  - Contrasting modes of evolution acting on the complex N locus for rust resistance
      in flax.
AB  - Three rust resistance specificities, N, N1 and N2, map to the complex N locus of
      flax. We used a degenerate PCR approach, with primers directed to the nucleotide
      binding site (NBS) domain characteristic of many plant resistance genes, to
      isolate resistance gene analogs (RGAs) from flax. One RGA clone detected RFLPs co
      segregating with alleles of the N locus. With this probe we isolated four related
      genes that occur within a 30kbp region and encode proteins with NBS and leucine
      rich repeat (LRR) domains and N-terminal Toll/Interleukin-1 Receptor homology
      (TIR) domains. One of these four genes was identified as the N resistance gene by
      sequence analysis of three mutant alleles and by transgenic expression. We
      isolated homologous genes from two flax lines containing the N1 or N2
      specificities and from flax lines carrying no N locus resistance specificities.
      Analysis of shared polymorphisms among this set of 18 N locus sequences revealed
      three groups of genes with independent lineages. Sequence exchanges have only
      occurred between genes within each group, but not between groups. Two of the
      groups contain only one sequence from each haplotype and probably represent
      orthologous genes. However, the third group contains two genes from each
      haplotype. We suggest that the re-assortment of variation by recombination/gene
      conversion at this locus is limited by the degree of sequence identity between
      genes.

PMID- 11576429
TI  - Identification of 4-coumarate:coenzyme A ligase (4CL) substrate recognition
      domains.
AB  - 4-coumarate:CoA ligase (4CL), the last enzyme of the general phenylpropanoid
      pathway, provides precursors for the biosynthesis of a large variety of plant
      natural products. 4 CL catalyzes the formation of CoA thiol esters of 4-coumarate
      and other hydroxycinnamates in a two step reaction involving the formation of an
      adenylate intermediate. 4 CL shares conserved peptide motifs with diverse
      adenylate-forming enzymes such as firefly luciferases, non-ribosomal peptide
      synthetases, and acyl:CoA synthetases. Amino acid residues involved in 4 CL
      catalytic activities have been identified, but domains involved in determining
      substrate specificity remain unknown. To address this question, we took advantage
      of the difference in substrate usage between the Arabidopsis thaliana 4 CL
      isoforms At4CL1 and At4CL2. While both enzymes convert 4-coumarate, only At4CL1
      is also capable of converting ferulate. Employing a domain swapping approach, we
      identified two adjacent domains involved in substrate recognition. Both substrate
      binding domain I (sbd I) and sbd II of At4CL1 alone were sufficient to confer
      ferulate utilization ability upon chimeric proteins otherwise consisting of
      At4CL2 sequences. In contrast, sbd I and sbd II of At4CL2 together were required
      to abolish ferulate utilization in the context of At4CL1. Sbd I corresponds to a
      region previously identified as the substrate binding domain of the adenylation
      subunit of bacterial peptide synthetases, while sbd II centers on a conserved
      domain of so far unknown function in adenylate-forming enzymes (GEI/LxIxG).
      At4CL1 and At4CL2 differ in nine amino acids within sbd I and four within sbd II,
      suggesting that these play roles in substrate recognition.

PMID- 11576430
TI  - Tissue-specific patterns of a maize Myb transcription factor are epigenetically
      regulated.
AB  - The maize p1 gene encodes a Myb-homologous regulator of red pigment biosynthesis.
      To investigate the tissue-specific regulation of the p1 gene, maize plants were
      transformed with constructs combining promoter and cDNA sequences of two alleles
      which differ in pigmentation patterns: P1-wr (white pericarp/red cob) and P1-rr
      (red pericarp/red cob). Surprisingly, all promoter/cDNA combinations produced
      transgenic plants with red pericarp and red cob (RR pattern), indicating that the
      P1-wr promoter and encoded protein can function in pericarp. Some of the RR
      patterned transgenic plants produced progeny plants with white pericarp and red
      cob (WR pattern), and this switch in tissue-specificity correlated with increased
      transgene methylation. A similar inverse correlation between pericarp
      pigmentation and DNA methylation was observed for certain natural p1 alleles,
      which have a gene structure characteristic of standard P1-wr alleles, but which
      confer red pericarp pigmentation and are consistently less methylated than
      standard P1-wr alleles. Although we cannot rule out the possible existence of
      tissue-specific regulatory elements within the p1 non-coding sequences or
      flanking regions, the data from transgenic and natural alleles suggest that the
      tissue-specific pigmentation pattern characteristic of the P1-wr phenotype is
      epigenetically controlled.

PMID- 11576433
TI  - The monarch butterfly controversy: scientific interpretations of a phenomenon.
AB  - The future development and use of agricultural biotechnology has been challenged
      by two preliminary studies indicating potential risk to monarch butterfly
      populations by pollen from corn engineered to express proteins from Bacillus
      thuringiensis. Likewise, these studies have also challenged the way in which
      science should be performed, published in scientific journals and communicated to
      the public at large. Herein, we provide a history of the monarch controversy to
      date. We believe a retrospective view may be useful for providing insights into
      the proper roles and responsibilities of scientists, the media and public
      agencies and the consequences when they go awry.

PMID- 11576434
TI  - Development and commercial use of Bollgard cotton in the USA--early promises
      versus today's reality.
AB  - Bollgard cotton is the trademark given to a number of varieties of cotton bio
      engineered to produce an insecticidal protein from Bacillus thuringiensis (Bt).
      When produced by the modified cotton plants, this protein controls certain
      lepidopterous cotton insect pests. Commercially available since 1996, these
      cotton varieties are purchased under a license agreement in which the growers pay
      a fee and agree to abide by the terms, which include a 1-year license to use the
      technology and agreement to participate in an insect resistance management
      program. Today, Bollgard cotton is grown on more than one-third of all cotton
      acreage in the USA. This product has reduced cotton production costs and
      insecticide use by providing an effective alternative to chemical insecticides
      for the control of tobacco budworm, Heliothis virescens; cotton bollworm,
      Helicoverpa zea; and pink bollworm, Pectinophora gossypiella. The specificity and
      safety profile of the Bt protein produced in planta in cotton was maintained. It
      has retained its selectivity for lepidopterous insects and lacks the
      characteristics found in potential allergenic proteins. Fiber quality, the
      agronomic characteristics of the plant and seed composition remain unchanged. New
      cotton technology is being developed to provide improved insect control and a
      wider spectrum of activity. These future products could further reduce
      insecticide use in the production of cotton, while maintaining the high level of
      safety and reliability that has been demonstrated by five seasons of Bollgard
      cotton use.

PMID- 11576435
TI  - Assessment of the food safety issues related to genetically modified foods.
AB  - International consensus has been reached on the principles regarding evaluation
      of the food safety of genetically modified plants. The concept of substantial
      equivalence has been developed as part of a safety evaluation framework, based on
      the idea that existing foods can serve as a basis for comparing the properties of
      genetically modified foods with the appropriate counterpart. Application of the
      concept is not a safety assessment per se, but helps to identify similarities and
      differences between the existing food and the new product, which are then subject
      to further toxicological investigation. Substantial equivalence is a starting
      point in the safety evaluation, rather than an endpoint of the assessment.
      Consensus on practical application of the principle should be further elaborated.
      Experiences with the safety testing of newly inserted proteins and of whole
      genetically modified foods are reviewed, and limitations of current test
      methodologies are discussed. The development and validation of new profiling
      methods such as DNA microarray technology, proteomics, and metabolomics for the
      identification and characterization of unintended effects, which may occur as a
      result of the genetic modification, is recommended. The assessment of the
      allergenicity of newly inserted proteins and of marker genes is discussed. An
      issue that will gain importance in the near future is that of post-marketing
      surveillance of the foods derived from genetically modified crops. It is
      concluded, among others that, that application of the principle of substantial
      equivalence has proven adequate, and that no alternative adequate safety
      assessment strategies are available.

PMID- 11576436
TI  - Trans-dominant suppression of plant TGA factors reveals their negative and
      positive roles in plant defense responses.
AB  - Salicylic acid (SA) is a key regulator for the induction of systemic acquired
      resistance (SAR), and NPR1 is a critical mediator for the biological effects of
      SA. Physical interactions between NPR1 and TGA factors, a conserved family of
      basic-leucine-zipper (bZip) proteins in plants, have suggested a role for these
      transcription factors in mediating SAR induction via the regulation of defense
      genes. To elucidate this function, we constructed a trans-dominant mutant that
      specifically eliminates DNA-binding activities of this class of bZip proteins in
      transgenic tobacco plants. Our results demonstrate that the loss of TGA DNA
      binding activities is correlated with suppression of two xenobiotic-responsive
      genes, GNT35 and STR246, and enhanced induction of pathogenesis-related (PR)
      genes by SA. In addition, these TGA-suppressed plants exhibited higher levels of
      PR gene induction by pathogen challenge and an enhanced SAR. These results
      suggest that TGA transcription factors serve both negative and positive
      regulatory roles in mediating plant defense responses.

PMID- 11576437
TI  - Hydrophobic residues within the predicted N-terminal amphiphilic alpha-helix of a
      plant mitochondrial targeting presequence play a major role in in vivo import.
AB  - A deletion and mutagenesis study was performed on the mitochondrial presequence
      of the beta-subunit of the F(1)-ATP synthase from Nicotiana plumbaginifolia
      linked to the green fluorescent protein (GFP). The various constructs were tested
      in vivo by transient expression in tobacco protoplasts. GFP distribution in
      transformed cells was analysed in situ by confocal microscopy, and in vitro in
      subcellular fractions by Western blotting. Despite its being highly conserved in
      different species, deletion of the C-terminal region (residues 48-54) of the
      presequence did not affect mitochondrial import. Deletion of the conserved
      residues 40-47 and the less conserved intermediate region (residues 18-39)
      resulted in 60% reduction in GFP import, whereas mutation of conserved residues
      within these regions had little effect. Further shortening of the presequence
      progressively reduced import, with the construct retaining the predicted N
      terminal amphiphilic alpha-helix (residues 1-12) being unable to mediate
      mitochondrial import. However, point mutation showed that this last region plays
      an important role through its basic residues and amphiphilicity, but also through
      its hydrophobic residues. Replacing Arg4 and Arg5 by alanine residues and
      shifting the Arg5 and Leu6 (in order to disturb amphiphilicity) resulted in
      reduction of the presequence import efficiency. The most dramatic effects were
      seen with single or double mutations of the four Leu residues (positions 5, 6, 10
      and 11), which resulted in marked reduction or abolition of GFP import,
      respectively. We conclude that the N-terminal helical structure of the
      presequence is necessary but not sufficient for efficient mitochondrial import,
      and that its hydrophobic residues play an essential role in in vivo mitochondrial
      targeting.

PMID- 11576438
TI  - Arabidopsis polyamine biosynthesis: absence of ornithine decarboxylase and the
      mechanism of arginine decarboxylase activity.
AB  - Unlike other eukaryotes, which can synthesize polyamines only from ornithine,
      plants possess an additional pathway from arginine. Occasionally non-enzymatic
      decarboxylation of ornithine could be detected in Arabidopsis extracts; however,
      we could not detect ornithine decarboxylase (ODC; EC 4. 1.1.17) enzymatic
      activity or any activity inhibitory to the ODC assay. There are no intact or
      degraded ODC sequences in the Arabidopsis genome and no ODC expressed sequence
      tags. Arabidopsis is therefore the only plant and one of only two eukaryotic
      organisms (the other being the protozoan Trypanosoma cruzi) that have been
      demonstrated to lack ODC activity. As ODC is a key enzyme in polyamine
      biosynthesis, Arabidopsis is reliant on the additional arginine decarboxylase
      (ADC; EC 4.1.1.9) pathway, found only in plants and some bacteria, to synthesize
      putrescine. By using site-directed mutants of the Arabidopsis ADC1 and
      heterologous expression in yeast, we show that ADC, like ODC, is a head-to-tail
      homodimer with two active sites acting in trans across the interface of the
      dimer. Amino acids K136 and C524 of Arabidopsis ADC1 are essential for activity
      and participate in separate active sites. Maximal activity of Arabidopsis ADC1 in
      yeast requires the presence of general protease genes, and it is likely that
      dimer formation precedes proteolytic processing of the ADC pre-protein monomer.

PMID- 11576439
TI  - Identification of a novel genetically controlled step in mycorrhizal
      colonization: plant resistance to infection by fungal spores but not extra
      radical hyphae.
AB  - Vesicular arbuscular mycorrhizal fungi infect plants by means of both spores and
      vegetative hyphae at early stages of symbiosis. Using 2500 M2 fast-neutron
      mutagenized seeds of the miniature tomato (Lycopersicon esculentum) cultivar,
      Micro-Tom, we isolated a mutant, M161, that is able to resist colonization in the
      presence of Glomus intraradices spores. The myc(-) phenotype of the mutant was
      stable for nine generations, and found to segregate as a single Mendelian
      recessive locus. The mutant exhibited morphological and growth-pattern
      characteristics similar to those of wild-type plants. Alterations of light
      intensity and day/night temperatures did not eliminate the myc(-) characteristic.
      Resistance to mycorrhizal fungal infection and colonization was also evident
      following inoculation with the fungi Glomus mosseae and Gigaspora margarita.
      Normal colonization of M161 was evident when mutant plants were grown together
      with arbuscular mycorrhizal-inoculated wild-type plants in the same growth
      medium. During evaluation of the pre-infection stages in the mutant rhizosphere,
      spore germination and appressoria formation of G. intraradices were lower by 45
      and 70%, respectively, than the rates obtained with wild-type plants. These
      results reveal a novel, genetically controlled step in the arbuscular mycorrhizal
      colonization process, governed by at least one gene, which significantly reduces
      key steps in pre-mycorrhizal infection stages.

PMID- 11576440
TI  - VFK1, a Vicia faba K(+) channel involved in phloem unloading.
AB  - In search of a K(+) channel involved in phloem transport we screened a Vicia faba
      cotyledon cDNA library taking advantage of a set of degenerated primers, flanking
      regions conserved among K(+) uptake channels. We cloned VFK1 (for Vicia faba K(+)
      channel 1) characterised by a structure known from the Shaker family of plant
      K(+) channels. When co-expressed with a KAT1 mutant in Xenopus oocytes,
      heteromers revealed the biophysical properties of a K(+) selective, proton
      blocked channel. Northern blot analyses showed high levels of expression in
      cotyledons, flowers, stem and leaves. Using in situ PCR techniques we could
      localise the K(+) channel mRNA in the phloem. In the stem VFK1 expression levels
      were higher in the lower internodes. There channel transcripts increased in the
      light and thus under conditions of increased photosynthate allocation. VFK1
      transcripts are elevated in sink leaves, and rise in source leaves during the
      experimental transition into sinks. Fructose- rather than sucrose- or glucose
      feeding via the petiole induced VFK1 gene activity. We therefore monitored the
      fructose sensitivity of the sieve tube potential through cut aphid stylets. In
      response to an 1 h fructose treatment the sieve tube potential shift increased
      from 19 mV to 53 mV per 10-fold change in K(+) concentration. Under these
      conditions K(+) channels dominated the electrical properties of the plasma
      membrane. Based on the phloem localisation and expression patterns of VFK1 we
      conclude that this K(+) channel is involved in sugar unloading and K(+)
      retrieval.

PMID- 11576441
TI  - Construct design for efficient, effective and high-throughput gene silencing in
      plants.
AB  - Post-transcriptional silencing of plant genes using anti-sense or co-suppression
      constructs usually results in only a modest proportion of silenced individuals.
      Recent work has demonstrated the potential for constructs encoding self
      complementary 'hairpin' RNA (hpRNA) to efficiently silence genes. In this study
      we examine design rules for efficient gene silencing, in terms of both the
      proportion of independent transgenic plants showing silencing, and the degree of
      silencing. Using hpRNA constructs containing sense/anti-sense arms ranging from
      98 to 853 nt gave efficient silencing in a wide range of plant species, and
      inclusion of an intron in these constructs had a consistently enhancing effect.
      Intron-containing constructs (ihpRNA) generally gave 90-100% of independent
      transgenic plants showing silencing. The degree of silencing with these
      constructs was much greater than that obtained using either co-suppression or
      anti-sense constructs. We have made a generic vector, pHANNIBAL, that allows a
      simple, single PCR product from a gene of interest to be easily converted into a
      highly effective ihpRNA silencing construct. We have also created a high
      throughput vector, pHELLSGATE, that should facilitate the cloning of gene
      libraries or large numbers of defined genes, such as those in EST collections,
      using an in vitro recombinase system. This system may facilitate the large-scale
      determination and discovery of plant gene functions in the same way as RNAi is
      being used to examine gene function in Caenorhabditis elegans.

PMID- 11576442
TI  - The auxin signal for protoplast swelling is perceived by extracellular ABP1.
AB  - Protoplasts of corn coleoptiles and Arabidopsis hypocotyls respond to the plant
      hormone auxin with a rapid change in volume. We checked the effect of antibodies
      directed against epitopes of auxin-binding protein 1 from Arabidopsis thaliana
      (AtERabp1) and Zea mays (ZmERabp1), respectively. Antibodies raised against the C
      terminus of AtERabp1 inhibited the response to auxin, while antibodies raised
      against a part of box a, the putative auxin-binding domain, induced a swelling
      response similar to that caused by auxin treatment. Synthetic C-terminal
      oligopeptides of ZmERabp1 also caused a swelling response. These effects occurred
      regardless of whether the experiments were carried out with homologous (anti
      AtERabp1 antibodies on Arabidopsis protoplasts or anti-ZmERabp1 antibodies in
      maize protoplasts) or heterologous immunological tools. The results indicate that
      the auxin signal for protoplast swelling is perceived by extracellular ABP1.

PMID- 11576443
TI  - The nuclear envelope in muscular dystrophy and cardiovascular diseases.
AB  - Considerable interest has been focused on the nuclear envelope in recent years
      following the realization that several human diseases are linked to defects in
      genes encoding nuclear envelope specific proteins, most notably A-type lamins and
      emerin. These disorders, described as laminopathies or nuclear envelopathies,
      include both X-linked and autosomal dominant forms of Emery-Dreifuss muscular
      dystrophy, dilated cardiomyopathy with conduction system defects, limb girdle
      muscular dystrophy 1B with atrioventricular conduction disturbances, and Dunnigan
      type familial partial lipodystrophy. Certain of these diseases are associated
      with nuclear structural abnormalities that can be seen in a variety of cells and
      tissues. These observations clearly demonstrate that A-type lamins in particular
      play a central role, not only in the maintenance of nuclear envelope integrity
      but also in the large-scale organization of nuclear architecture. What is not
      obvious, however, is why defects in nuclear envelope proteins that are found in
      most adult cell types should give rise to pathologies associated predominantly
      with skeletal and cardiac muscle and adipocytes. The recognition of these various
      disorders now raises the novel possibility that the nuclear envelope may have
      functions that go beyond housekeeping and which impact upon cell-type specific
      nuclear processes.

PMID- 11576444
TI  - Protein export from the nucleus.
AB  - The evolution of the nucleus imposed on eukaryotic cells the necessity to
      strictly control exchange of molecules between the nucleus and the remainder of
      the cell, not only to protect and correctly transmit genetic information, but
      also to coordinate nuclear and cytoplasmic functions. Studies over the past 10
      years have provided major insights into the molecular mechanisms responsible for
      transport of molecules between the nucleus and the cytoplasm. In addition,
      regulation of the nucleocytoplasmic distribution of diverse cellular factors has
      emerged as one of the most efficient mechanism to adapt gene expression to the
      cell environment, for example by controlling the access of transcriptional
      regulators to their target genes. In this review, we focus on the molecular basis
      of protein nuclear export that relies on interactions between targeting sequences
      present on the cargoes, specific export receptors or exportins and nuclear pore
      proteins, with special emphasis on the role of the Ran GTPase and associated
      proteins in this process.

PMID- 11576445
TI  - To find the road traveled to tumor immunity: the trafficking itineraries of
      molecular chaperones in antigen-presenting cells.
AB  - Molecular chaperones, both endoplasmic reticulum and cytosol derived, have been
      identified as tumor rejection antigens; in animal models, they can elicit
      prophylactic and therapeutic immune responses against their tumor of origin.
      Chaperone immunogenic activity derives from three principal characteristics: they
      bind an array of immunogenic (poly)peptides, they can be efficiently internalized
      by professional antigen-presenting cells, and once internalized, they traffic to
      a subcellular compartment(s) where peptide release can occur. Within the antigen
      presenting cell, chaperone-derived peptides can be assembled onto major
      histocompatibility class I molecules for presentation at the antigen-presenting
      cell surface, thereby yielding the requisite and specific CD8+ T-cell responses
      that contribute to the process of tumor rejection. Though it is clear that
      chaperones, in particular GRP94 (gp96), calreticulin and Hsp70, can elicit
      cellular immune responses, the subcellular basis of chaperone processing by
      antigen-presenting cells remains mysterious. In this review, we discuss recent
      reports describing the identification of a chaperone internalization receptor and
      the physiological release of chaperones from necrotic cells, and we present views
      on the trafficking pathways within antigen-presenting cells that may function to
      deliver the chaperone-associated peptides to subcellular organelles for their
      subsequent exchange onto major histocompatibility complex molecules.

PMID- 11576446
TI  - Regulation of organelle membrane fusion by Pkc1p.
AB  - Membrane fusion relies on complex protein machineries, which act in sequence to
      catalyze the fusion of bilayers. The fusion of endoplasmic reticulum membranes
      requires the t-SNARE Ufe1p, and the AAA ATPase p97/Cdc48p. While the mechanisms
      of membrane fusion events have begun to emerge, little is known about how this
      fusion process is regulated. We provide first evidence that endoplasmic reticulum
      membrane fusion in yeast is regulated by the action of protein kinase C.
      Specifically, Pkc1p kinase activity is needed to protect the fusion machinery
      from ubiquitin-mediated degradation.

PMID- 11576447
TI  - Yeast ribosomes bind to highly purified reconstituted Sec61p complex and to
      mammalian p180.
AB  - To determine whether the yeast Sec61p translocation pore is a high-affinity
      ribosome receptor in the endoplasmic reticulum, we isolated the Sec61p complex
      using an improved protocol in which contaminants found previously to be
      associated with the complex are absent. The purified complex, which contains
      Sec61p with an amino terminal hexahistidine tag, was active since it rescued a
      sec61-3 post-translational translocation defect in a reconstituted system. Co
      reconstitution of the Sec61p and Sec63p complexes into liposomes failed to
      support post-translational translocation, suggesting that Sec62p is required for
      this process. By Scatchard analysis, the purified Sec61p complex bound to yeast
      ribosomes when reconstituted into liposomes with a KD of 5.6 nM, a value similar
      to the KD obtained when ribosome binding to total microsomal protein was measured
      (2.7 nM). In addition, a mammalian protein, p180, which has been proposed to be a
      ribosome receptor, was expressed in yeast, and endoplasmic reticulum-derived
      microsomes isolated from this strain exhibited approximately 2.3-fold greater
      binding to yeast ribosomes. Despite this increase in ribosome binding, neither co
      nor post-translational translocation was compromised in vivo. In sum, our data
      suggest that the Sec61p complex is a ribosome receptor in the yeast endoplasmic
      reticulum membrane.

PMID- 11576448
TI  - Actin microfilaments facilitate the retrograde transport from the Golgi complex
      to the endoplasmic reticulum in mammalian cells.
AB  - The morphology and subcellular positioning of the Golgi complex depend on both
      microtubule and actin cytoskeletons. In contrast to microtubules, the role of
      actin cytoskeleton in the secretory pathway in mammalian cells has not been
      clearly established. Using cytochalasin D, we have previously shown that
      microfilaments are not involved in the endoplasmic reticulum-Golgi membrane
      dynamics. However, it has been reported that, unlike botulinum C2 toxin and
      latrunculins, cytochalasin D does not produce net depolymerization of actin
      filaments. Therefore, we have reassessed the functional role of actin
      microfilaments in the early steps of the biosynthetic pathway using C2 toxin and
      latrunculin B. The anterograde endoplasmic reticulum-to-Golgi transport monitored
      with the vesicular stomatitis virus-G protein remained unaltered in cells treated
      with cytochalasin D, latrunculin B or C2 toxin. Conversely, the brefeldin A
      induced Golgi membrane fusion into the endoplasmic reticulum, the Golgi-to
      endoplasmic reticulum transport of a Shiga toxin mutant form, and the subcellular
      distribution of the KDEL receptor were all impaired when actin microfilaments
      were depolymerized by latrunculin B or C2 toxin. These findings, together with
      the fact that COPI-coated and uncoated vesicles contain beta/gamma-actin
      isoforms, indicate that actin microfilaments are involved in the endoplasmic
      reticulum/Golgi interface, facilitating the retrograde Golgi-to-endoplasmic
      reticulum membrane transport, which could be mediated by the orchestrated
      movement of transport intermediates along microtubule and microfilament tracks.

PMID- 11576449
TI  - Elevated endosomal pH in HeLa cells overexpressing mutant dynamin can affect
      infection by pH-sensitive viruses.
AB  - Many viruses gain access to the cell via the endosomal route and require low
      endosomal pH for infectivity. The GTPase dynamin is essential for clathrin
      dependent endocytosis, and in HeLa cells overexpressing the nonfunctional
      dynaminK44A mutant the formation of clathrin-coated vesicles is halted. HRV2, a
      human minor group rhinovirus, is internalized by members of the low-density
      lipoprotein receptor family in a clathrin-independent manner. The low endosomal
      pH then leads to conversion of the capsid to C-antigen, which is required for
      release (uncoating) and transfer of the viral RNA into the cytosol and de novo
      synthesis of infectious virus. We here demonstrate that overexpression of
      dynaminK44A reduces this antigenic conversion and results in diminished viral
      synthesis. In contrast, lysosomal degradation is unaffected. The kinetics of the
      formation of C-antigen in vitro and in vivo suggest that the pH in endosomes is
      elevated by about 0.4 units upon overexpression of dynaminK44A. As a consequence,
      HRV2 uncoating is diminished early after internalization but attains control
      levels upon prolonged internalization. Thus, overexpression of dynaminK44A, in
      addition to trafficking defects, results in an elevated endosomal pH and thereby
      affects virus infection and most likely endosomal sorting and processing.

PMID- 11576450
TI  - Vacuolar sorting determinants within a plant storage protein trimer act
      cumulatively.
AB  - The mechanism for vacuolar sorting of seed storage proteins is as yet poorly
      understood and no receptor has been identified to date. The homotrimeric
      glycoprotein phaseolin, which is the major storage protein of the common bean,
      requires a transient tetrapeptide at the C-terminus for its vacuolar sorting. A
      mutated construct without the tetrapeptide is secreted. We show here that
      coexpression of wild-type phaseolin and the mutated, secreted form in transgenic
      tobacco results in the formation of mixed trimers and partial vacuolar delivery
      of the mutated polypeptides and partial secretion of wild-type polypeptides. This
      indicates that the sorting signal has a cumulative effect within a phaseolin
      trimer. The result is discussed in the light of the hypothesized mechanisms for
      vacuolar sorting of seed storage proteins.

PMID- 11576451
TI  - Biophysical modelling of proton radiation effects based on amorphous track
      models.
AB  - PURPOSE: To define a photon-equivalent dose in charged particle therapy one needs
      to know the RBE (Relative Biological Effectiveness) in the target region as well
      as in the surrounding tissue. RBE estimates are difficult since both the physical
      input parameters, i.e. LET distributions, and, even more so, the biological input
      parameters, i.e. cell nucleus size and local response, are not known in general.
      Track structure theory provides a basis for predicting dose-response curves for
      particle irradiation. There are (at least) two somewhat different algorithms: the
      Amorphous Track Partition model (ATP) and the Amorphous Track Local effect model
      (ATL). Both have been reported to give good agreement with observed
      radiobiological data. We were interested in a general comparison and in the
      predictive power of these models for protons. MATERIALS AND METHODS: We compared
      the principles of the two track structure approaches. The general dependencies of
      the model predictions on the input parameters are investigated. The model
      predictions for protons with respect to cell survival of V79 cells are compared
      with measurements. RESULTS: Although based on similar assumptions, the
      application of track structure theory in terms of the computational procedure is
      different for the two models. The ATP model provides a set of equations to
      predict inter- and intratrack radiation response whereas the ATL model is based
      on Monte Carlo simulations. One conceptual difference is the use of average doses
      in subtargets in the ATP model compared with the use of local doses in
      infinitesimal compartments in the ATL model. The ATP concept introduces an
      empirical scaling of the cross-section from subcellular to cellular response. The
      ATL concept inherently requires a critical adjustment of parameters handling the
      high local dose region near the track centre. The models predict proton survival
      curves reasonably well but neither shows good agreement with experimental data
      over the entire range of proton energy and absorbed dose considered. CONCLUSION:
      Designed for heavy ion applications, the models show weaknesses in the prediction
      of proton radiation effects. Amorphous track models are based on assumptions
      about the properties of the biological target and the radiation field that can be
      questioned. In particular, the assumption of subtargets and the
      multitarget/single-hit response function on one hand and the parameterization of
      radial dose and high dose cellular response on the other hand leave question
      marks.

PMID- 11576452
TI  - Relationship between cellular radiosensitivity and DNA damage measured by comet
      assay in human normal, NBS and AT fibroblasts.
AB  - PURPOSE: To study the relationship between cellular radiosensitivity and DNA
      damage measured by the comet assay. MATERIALS AND METHODS: Experiments were
      performed with nine human fibroblast lines (six normal, one NBS, and two AT).
      Cellular radiosensitivity was determined by colony assay and DNA damage was
      assessed by the comet assay. RESULTS: The cellular radiosensitivity of the
      fibroblast lines used covered a broad range with SF2 values varying between 1.3%
      and 53%. The comets analysed immediately after irradiation with doses up to 5 Gy
      showed marked differences among the cell lines; the relative initial tail moment
      at a dose of 5 Gy, ITM5, varied from 2.7+/-0.2 to 5.0+/-0.3. This variation was
      considered not to result from different numbers of DNA strand breaks induced but
      from differences in chromatin structure. There was an inverse correlation between
      SF2 and ITM5, i.e. radiosensitive cell lines exhibited a higher initial tail
      moment than radioresistant cell lines. In contrast, the repair kinetics measured
      with the comet assay for a dose of 2Gy followed by an incubation of up to 2h
      showed little variation and were found not to correlate with SF2. Repair kinetics
      as well as the amount of residual damage measured by this version of the comet
      assay were fairly similar to those measured by the alkaline unwinding technique
      and unlike that measured by neutral gel electrophoresis, indicating that this
      comet assay detects primarily single-strand breaks and alkali-labile sites, not
      double-strand breaks. CONCLUSIONS: The correlation between SF2 and the initial
      tail moment at 5 Gy found here suggests that the cellular radiosensitivity of
      human fibroblasts also depends on the chromatin structure.

PMID- 11576453
TI  - Radiation response of apoptosis in C57BL/6N mouse spleen after whole-body
      irradiation.
AB  - PURPOSE: Primary conditioning low dose irradiation suppresses the molecular
      responses against secondary challenge high dose irradiation; this phenomenon has
      been termed the radioadaptive response. The mechanism of the radioadaptive
      response is not yet clear. This study was undertaken to elucidate the radiation
      response of apoptosis in mouse spleen after whole-body irradiation. MATERIALS AND
      METHODS: The induction of apoptosis was analysed in the spleens of C57BL/6N mice
      after chronic irradiation with gamma-rays at 1.5 Gy (0.001 Gy/min for 25 h)
      followed by challenge irradiation with X-rays at 3.0Gy (1 Gy/min). RESULTS:
      Accumulation of p53 and Bax, and the induction of apoptosis were observed dose
      dependently in mouse spleen 12 h after acute irradiation at a high dose-rate.
      However, it was found that there was significant suppression of the accumulation
      of p53 and Bax, and induction of apoptosis 12 h after challenge irradiation at
      3.0Gy at a high dose-rate following chronic preirradiation at 1.5Gy at a low dose
      rate. In addition, the combination of pre-irradiation at 1.5Gy at a high dose
      rate and challenge irradiation at 3.0Gy at a high dose-rate could not suppress
      the accumulation of p53 and Bax or the induction of apoptosis. CONCLUSIONS:
      Chronic pre-irradiation at a low dose-rate suppressed Bax-mediated apoptosis.
      These findings suggest that the radioadaptive response in mouse spleen may be due
      to a suppression of p53-mediated apoptosis.

PMID- 11576454
TI  - Impact of pulmonary metastases of the R1H-tumour on radiation tolerance of rat
      lung.
AB  - PURPOSE: The aim was to investigate the influence of pulmonary metastases of the
      rhabdomyosarcoma R1H on the radiation response of the lung of the WAG/Rij rat.
      MATERIAL AND METHODS: Three groups of animals were investigated: metastases-free
      animals treated with fractionated irradiation of the lungs; metastases-bearing
      animals receiving no irradiation; and metastases-bearing animals treated with
      fractionated irradiation initiated 14, 21 or 28 days after induction of pulmonary
      metastases of the R1H-tumour by i.v. injection of viable tumour cells. Metastases
      were thus treated at various well-defined sizes. Total doses of 20-60Gy were
      applied in fractions of 2 Gy within 11 days. Complication rate and survival time
      were used as endpoints. RESULTS: About 2 months after onset of irradiation
      treatment, animals had to be sacrificed because of severe respiratory distress
      either caused by irradiation-induced lung damage (median 57 days, range 36-77
      days), or because of development of lung metastases (65, 20-160 days). A decrease
      of the ED(50) (dose required to induce lethal lung damage in 50% of irradiated
      animals) was determined for metastases-bearing animals. This effect increased
      with metastatic volume. CONCLUSIONS: The results suggest that the presence of
      tumours in the lung decreased the lung tolerance to radiation. This effect can
      hardly be explained by a reduction in functional lung volume by metastatic
      volume.

PMID- 11576455
TI  - Cytotoxicity of 125I-oestrogen decay in non-oestrogen receptor-expressing human
      breast cancer cells, MDA-231 and oestrogen receptor-expressing MCF-7 cells.
AB  - PURPOSE: To compare the cytotoxicity of 125I-oestrogen (E-17alpha[125I]iodovinyl
      11betamethoxyoestradiol or 125IVME2) decay accumulation in human breast
      adenocarcinoma cells that do not express oestrogen receptor (ER) (MDA-231 cells)
      with human breast adenocarcinoma cells that do express ER (MCF-7 cells).
      MATERIALS AND METHODS: MDA-231 cells were labelled with 125IVME2 or
      [125I]iododeoxyuridine (125IdU), frozen for decay accumulation, thawed and then
      plated for colony formation. gamma-irradiation survival was also determined. A
      whole-cell 3H-oestrogen-binding assay and a specific-binding assay were used to
      detect ER. RESULTS: No MDA-231 cell killing by accumulated 125IVME2 decays (up to
      440 dpc) was observed but ER-positive MCF-7 cells were killed by 125IVME2
      (D(o)=28 dpc). MDA-231 cells were not significantly more radioresistant to gamma
      rays (D(o)=1.7Gy for MDA-231 cells; 1 Gy for MCF-7 cells) or to 125IdU decays
      (D(o)= 44dpc for MDA-231 cells; 30 dpc for MCF-7 cells). No ER were detected in
      MDA-231 cells. CONCLUSIONS: ER-negative cells, MDA-231, are not killed by
      125IVME2 decay accumulation. It is speculated that without ER (required to
      translocate the 125IVME2 to its nuclear target), formation of the 125IVME2-ER-DNA
      oestrogen-response element (ERE) complex and subsequent specific irradiation of
      the DNA at the ERE cannot occur. These results support the hypothesis that the
      nuclear genome is a critical target for radiation-induced cell death.

PMID- 11576456
TI  - Solar UV radiation: differential effectiveness of UVB subcomponents in causing
      cell death, micronucleus induction and delayed expression of heritable damage in
      human hybrid cells.
AB  - PURPOSE: To determine the effectiveness of two UV spectra with different UVB
      components for cell kill and micronucleus induction in irradiated human HeLaxskin
      fibroblast (CGL1) hybrid cells and their progeny. To determine the presence of
      reactive oxygen species (ROS) in the progeny of the irradiated cells at various
      post-irradiation times and their relationship with induced delayed biological
      effects. MATERIAL AND METHODS: A commercial solar ultraviolet simulator was used.
      Two different filters were employed: the first transmitted radiation with
      lambda>284nm and the second radiation with lambda>293nm. The resulting spectra
      have different UVB components (lambda between 284 and 320nm, 19 W/m(2), and
      between 293 and 320nm, 13 W/m(2)) and the same UVA component (lambda between 320
      and 400nm, 135 W/m(2)). CGL1 cells were irradiated with various doses. Clonogenic
      survival and micronucleus formation were scored in the irradiated cells and their
      progeny. ROS were detected by incubation of cultures at various post-irradiation
      times with dichlorodihydrofluorescein diacetate followed by flow cytometric
      measurement of the final product, dichlorofluorescein. RESULTS: The biological
      effectiveness of the lambda>284nm spectrum was higher by a factor of 3 compared
      to the lambda>293nm spectrum for cell kill, and by a factor of 5 for micronucleus
      induction. No delayed cell death or micronucleus formation was found in the
      progeny of cells exposed to lambda>293nm, while a large and dose-dependent effect
      was found in the progeny of cells exposed to lambda>284nm for both of these
      endpoints. ROS levels above those in unirradiated controls were found only in the
      progeny of cells exposed to the lambda>284nm spectrum. CONCLUSIONS: The spectrum
      with lambda>284nm was more effective than that with lambda>293nm for induction of
      cell kill and micronucleus formation in the directly irradiated cells as well as
      induction of delayed effects in the progeny in the form of delayed reproductive
      death and micronucleus formation. The presence of ROS in the progeny of the
      irradiated cells may be the cause of the delayed effects.

PMID- 11576457
TI  - Detection of stable chromosome aberrations by FISH in A-bomb survivors:
      comparison with previous solid Giemsa staining data on the same 230 individuals.
AB  - PURPOSE: To evaluate the relative abilities of the solid Giemsa staining
      (conventional) and fluorescence in situ hybridization (FISH) methods in the
      detection of stable chromosome aberrations in the peripheral blood lymphocytes of
      A-bomb survivors. MATERIALS AND METHODS: Lymphocytes from a total of 230 A-bomb
      survivors for whom prior chromosome aberration data had been obtained by the
      conventional method were recently examined afresh using FISH in which chromosomes
      1, 2 and 4 were painted with composite probes. RESULTS: It was found that the
      early use of the solid Giemsa staining method had allowed the detection of
      translocations with a mean frequency of 73% of the value for the genome
      equivalent translocation frequency (F(G)) that was now obtained using FISH. The
      disparity may at least in part be due to the reciprocal exchange of seemingly
      identical amount of chromosome material; such exchanges can escape detection by
      the conventional method but can be readily identified using FISH. CONCLUSION: It
      has previously been established that the conventional method can detect about 20%
      of radiation-induced translocations as abnormal monocentric chromosomes. Present
      results indicate that an additional 50% can be detected if proper karyotyping is
      conducted and the remaining 30% are not likely to be detected unless FISH or
      banding methods are used. Thus, solid Giemsa staining accompanied by karyotyping
      may not be quite as unsuitable as is generally assumed for retrospective
      biodosimetry analyses, which deal mainly with stable aberrations.

PMID- 11576458
TI  - Survival, lung clearance, dosimetry and gross pathology of rats exposed to either
      NpO2 or PuO2 aerosols.
AB  - PURPOSE: To compare survival, lung dosimetry and gross pathology after inhalation
      exposure of rats to either NpO2 or industrial PuO2 aerosols with similar
      granulometric parameters. Because the specific alpha activity ratio Pu/Np is
      about 600, a much more homogeneous lung irradiation was expected for NpO2.
      MATERIALS AND METHODS: Male Sprague Dawley rats were exposed once and their lung
      burdens were measured by X-ray spectrometry at different times post-exposure up
      to death. The time-course of doses delivered to the lungs were estimated, taking
      into account individual lung clearance parameters and body and lung weights.
      Gross lung pathologies were scored at autopsy. RESULTS: In the range of initial
      lung deposits (ILD) studied (0.1-4 kBq), lung clearance impairment and reduced
      lifespan were only observed after exposure to NpO2. For similar ILD or doses, the
      highest incidences of lung lesions assumed to be tumours were observed for NpO2
      with a saturation of lung tumour induction for doses larger than 8 Gy (ILD:
      1.5kBq). Up to 22Gy (ILD: 3.5kBq), such saturation was not observed for PuO2.
      CONCLUSIONS: NpO2 appears much more toxic than PuO2. Before saturation, lung
      tumour incidence increased nearly linearly with dose, the slope of the curve for
      NpO2 being about twice as steep as that for PuO2.

PMID- 11576459
TI  - Clinical tolerance and profile of cytokine induction in healthy volunteers
      following the simultaneous administration of ifn-alpha and the synthetic
      immunomodulator murabutide.
AB  - As the therapeutic use of interferon-alpha (IFN-alpha) is limited by a dose
      dependent toxicity and variable efficacy, ways of improving the therapeutic index
      of the cytokine are being sought. Murabutide (N-acetyl muramyl-L-alanyl-D
      glutamine-O-n-butyl-ester) (ISTAC Biotechnology, Lille, France) is a safe
      synthetic and clinically acceptable immunomodulator that enhances the biologic
      activities of IFN-alpha in different experimental models. We evaluated in healthy
      human volunteers tolerance of the coadministration of Murabutide with increasing
      doses of IFN-alpha. The simultaneous administration of the two drugs was well
      tolerated without any increased or prohibiting toxicity, and all recipients
      experienced side effects that were similar to those observed after the
      administration of IFN-alpha alone. We also profiled the serum levels of cytokines
      induced following coinjection of the two drugs. We mostly detected an induction
      of anti-inflammatory cytokines and of human immunodeficiency virus type 1 (HIV-1)
      suppressive beta-chemokines, in the absence of release of key proinflammatory
      cytokines. Therefore, the simultaneous administration of Murabutide and IFN-alpha
      is well tolerated and does not lead to increased toxicity. In addition, the
      selectivity in the profile of cytokines and chemokines induced following the
      coadministration of Murabutide and IFN-alpha points to the potential use of this
      combination in the treatment of inflammatory diseases and chronic viral
      infections.

PMID- 11576460
TI  - Interferon-induced rat Mx proteins confer resistance to Rift Valley fever virus
      and other arthropod-borne viruses.
AB  - Mx proteins belong to the interferon (IFN)-induced antiviral defense. The rat
      genome contains three Mx genes, ratMx1, ratMx2, and ratMx3. The Mx gene products
      differ in their subcellular localization and antiviral specificity. The nuclear
      ratMx1 protein confers resistance to influenza A virus, and the cytoplasmic
      ratMx2 is active against vesicular stomatitis virus (VSV), whereas the
      cytoplasmic ratMx3 protein is antivirally inactive. To investigate the antiviral
      potential of the rat Mx proteins against arboviruses, a phylogenetically diverse
      group of viruses that frequently infect rodents, we studied the replication of
      LaCrosse virus (LACV). Rift Valley fever virus (RVFV) (both family Bunyaviridae),
      and Thogoto virus (THOV) (family Orthomyxoviridae). To that end, we used
      transfected Vero cells constitutively expressing one of the rat Mx proteins. We
      observed that the antiviral activity of rat Mx proteins against these arboviruses
      correlates with their intracellular localization: ratMx1 is active against THOV,
      which replicates in the nucleus, whereas ratMx2 inhibits bunyaviruses that
      replicate in the cytoplasm. The results indicate that rats have evolved two Mx
      proteins to efficiently control viruses with different replication strategies.

PMID- 11576461
TI  - Influence of IFN-alpha on plasma erythropoietin levels in patients with hepatitis
      B virus-associated chronic active hepatitis.
AB  - The influence of 3-month interferon-alpha (IFN-alpha) treatment on plasma
      erythropoietin (EPO) concentration in patients with chronic active hepatitis
      (CAH) induced by hepatitis B virus (HBV) infection was investigated. The study
      was carried out in 44 nonanemic patients divided into two groups: CAH B, 30
      subjects not treated with IFN-alpha, and CAH B-IFN, 14 subjects treated with IFN
      alpha for the first 3 months of the study (5 MU/m(2) body surface subcutaneously
      (s.c.) three times per week). In all patients, blood samples were taken at the
      beginning of the study (0) and after 1, 2, 3, 6, 9, and 12 months of observation.
      At the beginning, plasma EPO levels in the CAH B (27.8 +/- 2.21 mU/ml) and CAH B
      IFN (27.3 +/- 3.04 mU/ml) groups did not differ significantly from each other and
      were significantly higher (p < 0.0001) than in healthy subjects (10.4 +/- 1.06
      mU/ml). In patients in the CAH B group, plasma EPO concentrations did not change
      significantly during the whole observation period. In patients in the CAH B-IFN
      group, a transient, significant increase in plasma EPO level was found. The
      highest plasma EPO concentration in this group was noted after the third month of
      treatment (41.1 +/- 3.41 mU/ml). In conclusion, patients with CAH induced by HBV
      infection are characterized by increased plasma EPO concentrations, and IFN-alpha
      treatment in these patients causes a transient increase in the plasma EPO level.

PMID- 11576462
TI  - Phenotypic and ultrastructural characteristics of bronchoalveolar lavage cells of
      lentivirus-infected lambs treated with recombinant ovine IFN-tau.
AB  - Ovine lentivirus (OvLV) belongs to the family Retroviridae and closely resembles
      the human immunodeficiency virus (HIV). Pulmonary lesions in OvLV-infected sheep
      consist of lymphoid interstitial pneumonia (LIP) and lymphocytic alveolitis.
      Similar pulmonary lesions occur in up to 40% of HIV-infected children and in some
      adults with AIDS. Interferon-tau (IFN-tau), a type I IFN, is produced by
      trophectoderm of ruminant conceptuses and is the pregnancy recognition signal in
      these species. To evaluate changes in phenotypes of bronchoalveolar lavage (BAL)
      cells of OvLV-infected lambs treated with recombinant ovine IFN-tau (rOvIFN-tau),
      24 lambs were randomly allocated to one of four groups (n = 6 per group): 1, no
      virus + placebo (NVP); 2, no virus + rOvIFN-tau (NVI); 3, virus + placebo (VP);
      4, virus + rOvIFN-tau (VI). The BAL cells from 3 lambs in each group were labeled
      with monoclonal antibodies (mAb) to cell surface markers at 16 weeks of
      treatment, and cells from the remaining 3 lambs in each group were labeled with
      mAb at 34 weeks of treatment. After labeling, BAL cells were analyzed by flow
      cytometry. The morphology of BAL cells from all experimental lambs was examined
      by transmission electron microscopy (TEM). At week 16, no differences in the
      relative proportions of BAL cell phenotypes were detected among the experimental
      groups. At week 34, VI lambs had higher proportions of CD8(+), gammadelta(+), MHC
      class II(+), and L-selectin (LS(+)) BAL cells compared with VP lambs. Higher
      proportions of CD14(+) and CD44(+) cells were found in VP lambs compared with NVP
      lambs at 34 weeks. OvLV-like particles were detected only in bronchoalveolar
      macrophages of VP lambs. In this study, rOvIFN-tau increased the proportions of
      primary antiviral gammadelta(+) and CD8(+) immune cells in OvLV-infected lambs.
      This may represent a cellular mechanism to explain the antiviral and therapeutic
      efficacy of this cytokine, in addition to its direct antiviral effect. However,
      because the actual number of cells labeled with mAb CD8 was low and some subsets
      of gammadelta cells may coexpress the CD8 marker, further studies are necessary
      to better define the role of rOvIFN-tau in the modulation of these cells in vivo.

PMID- 11576463
TI  - Immune responsiveness following academic stress in first-year medical students.
AB  - Many studies illustrate that physical or psychologic stressors can alter human
      immune function, which might predispose one to an increased susceptibility to
      infections. In the present study, we monitored immune responsiveness in 16 first
      year medical students (age 23.8 +/- 2.2 years) during the first examination
      session. Baseline blood samples were collected 30 days prior to the first
      examination session. Subsequently, subjects were randomly assigned to two groups,
      and blood samples were collected at 24 h (POST24h) or 48 h (POST48h) after an
      examination. The percentage of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+),
      CD3(+)CD45RO(+), CD3(+)CD45RA(+), CD3(-)CD16(+)56(+), CD19(+), and CD14(+) cells
      in whole blood was examined to determine changes in circulating immune cell
      populations. Activation of peripheral blood mononuclear cells (PBMC) with a
      mixture of phorbol myristate acetate (PMA) and ionomycin or lipopolysaccharide
      (LPS) for 4 h was used to assess the distribution of interleukin-2 (IL-2)
      secreting or interferon-gamma (IFN-gamma)-secreting CD4(+) and CD8(+) cells, as
      well as IL-1alpha-secreting CD14(+) cells. Activation with a combination of
      phytohemagglutinin (PHA) and LPS was used to assess secretion of IL-2, IFN-gamma,
      IL-4, IL-10, soluble IL-2 receptor-alpha (sIL-2Ralpha), IL-1beta, and IL-1R
      antagonist (IL-1Ra) by PBMC in 48-h cell culture. A significantly higher level of
      total T cells was found at POST24h, and CD14(+) was elevated at both POST24h and
      POST48h. The percentage of CD4(+) and CD8(+) cells significantly declined at
      POST24 and POST48h. A significant elevation in the percentage of memory T cells
      was observed at POST48h, whereas the percentage of naive T cells was elevated at
      POST24h and POST48h. These changes were accompanied by a significant decline in
      percentage of natural killer (NK) cells 24 h after the examination. The
      percentage of IL-2-producing CD4(+) and CD8(+) cells was significantly lower at
      POST24h, and the percentage of CD8(+)IFN-gamma(+) cells significantly declined at
      POST48h. The percentage of CD14(+)IL-1alpha(+) significantly declined at both
      POST24 and POST48h. A significant decrease was observed in IL-2 secretion 24 h
      after the examinations, and the secretion of IL-4 and IL-1beta significantly
      declined at POST48h. No changes in IFN-gamma, IL-10, sIL-2Ralpha, and IL-1Ra
      secretion were observed. We conclude that the stress outcomes of academic
      examinations in first-year medical students can significantly alter immune cell
      distribution and in vitro production and secretion of specific cytokines.

PMID- 11576464
TI  - Interleukin-11 induces osteoblast differentiation and acts synergistically with
      bone morphogenetic protein-2 in C3H10T1/2 cells.
AB  - Interleukin-11 (IL-11) is a pleiotropic cytokine that supports various types of
      hematopoietic cell growth and is involved in bone resorption. We report here the
      involvement of recombinant human IL-11 (rHuIL-11) in osteoblast differentiation
      in mouse mesenchymal progenitor cells, C3H10T1/2. rHuIL-11 alone increased
      alkaline phosphatase (ALP) activity and upregulated expression levels of
      osteocalcin (OC), bone sialo protein (BSP), and parathyroid hormone receptor
      (PTHR) mRNA. rHuIL-11 had no effect on expression of type II collagen, peroxisome
      proliferator-activated receptor-gamma2 (PPAR-gamma2), adipocyte fatty acid
      binding protein P2 (aP2), and myogenic MyoD protein (MyoD). Recombinant human
      bone morphogenetic protein (rHuBMP)-2 increased ALP activity and mRNA expression
      of these genes except for MyoD. The expression patterns of ALP activity and
      osteoblast-specific or chondrocyte-specific genes suggest that rHuIL-11 may be
      involved in early differentiation of osteoblasts at a step earlier than that
      which is affected by rHuBMP-2. In support of this hypothesis, combined treatment
      with rHuIL-11 and rHuBMP-2 synergistically increased ALP activity and mRNA
      expression of OC and type II collagen, rHuIL-11 also abrogated the increased
      levels of PPAR-gamma2, aP2 mRNA caused by rHuBMP-2. Our results suggest that
      rHuIL-11 alone and in combination with rHuBMP-2 can induce osteoblastic
      differentiation of progenitor cells and plays an important role in osteogenesis.

PMID- 11576465
TI  - Mechanism of antitumor activity of a single-chain interleukin-12 IgG3 antibody
      fusion protein (mscIL-12.her2.IgG3).
AB  - We have constructed an antibody interleukin-12 (IL-12) fusion protein (mscIL
      12.her2.IgG3) that demonstrates significant antitumor activity against the murine
      carcinoma CT26-expressing human HER2/neu. We now report that this antitumor
      activity is dose dependent and comparable to or better than recombinant murine IL
      12 (rMuIL-12) using subcutaneous and metastatic models of disease. The antitumor
      activity of mscIL-12.her2.IgG3 is reduced in Rag2 knockout mice, suggesting that
      T cells play a role in tumor rejection. In SCID-beige mice, the antitumor
      activity is further reduced, suggesting that natural killer (NK) cells or
      macrophages or both are also important. The isotype of the antibody response to
      HER2/neu is consistent with a switch from a Th2 to a Th1 immune response and the
      infiltration of mononuclear cell in tumors from mice treated with mscIL
      12.her2.IgG3. Immunohistochemistry reveals that mscIL-12.her2.IgG3 is
      antiangiogenic. Thus, the mechanism of the antitumor activity exhibited by mscIL
      12.her2.IgG3 is highly complex and involves a combination of T and NK cell
      activity, a switch to a Th1 immune response, and antiantiogenic activity. This is
      the first study comparing the in vivo antitumor activity of an antibody-IL-12
      fusion protein and free IL-12. Our results suggest that antibody-IL-12 fusion
      proteins may be useful for the treatment of human cancer.

PMID- 11576466
TI  - Low-dose orally administered type I interferon reduces splenic B cell numbers in
      mice.
AB  - The beneficial effects of low-dose orally administered type I interferon (LDOA
      IFN) have been demonstrated in various animal models of disease and in some human
      clinical trials. The mechanisms by which LDOA IFN therapy has its effects,
      however, remain to be established. In the present study, groups of mice were
      administered 10 IU murine IFN-alpha/beta (MuIFN-alpha/beta) orally for 7 days.
      Spleens were then collected and analyzed. No differences were detected between
      the spleen weights of treated mice compared with controls, although reductions in
      total splenic white blood cell (WBC) number ranging from 15.5% to 35% were
      observed. Further analysis showed this reduction to be largely restricted to the
      B cell population, with only minor reductions in CD4(+) or CD8(+) populations
      being detected. Dose-response studies showed the WBC loss from the spleen to be
      optimal at 1 IU MuIFN-alpha/beta, whereas both higher and lower doses showed less
      significant effects. Time course studies show these effects had developed after 2
      days of treatment. It is hypothesized that this observed WBC movement from the
      spleen is part of the mechanism of action of LDOA IFN.

PMID- 11576467
TI  - The neutralization of interferons by antibody. I. Quantitative and theoretical
      analyses of the neutralization reaction in different bioassay systems.
AB  - The highly specific ability of antibodies to inhibit the biologic activity of
      cytokines or other therapeutic proteins is widely used in research and a subject
      of increasing clinical importance. The need exists for a standardized approach to
      the reporting of neutralizing antibody potency soundly based on theoretical and
      practical considerations and tested by experimental data. Pursuant to the
      original studies of Kawade on the theoretical and functional aspects of
      neutralization of interferons (IFN), experimental data were obtained by different
      laboratories employing varied methodology to address two hypotheses concerning
      the nature of IFN neutralization reactions, based on a derived formula that
      allows expression of neutralizing power as the reduction of 10 laboratory units
      (LU)/ml to 1 LU/ml, the end point of most bioassays. Two hypotheses are posed:
      (1) antibody acts to neutralize a fixed amount of biologically active IFN
      molecules, or (2) antibody reduces IFN activity in a set ratio of added/residual
      biologically active IFN. The first, or fixed amount, hypothesis relates to the
      reactivity of high-affinity antibodies neutralizing equimolar amounts of antigen,
      whereas the second, or constant proportion, hypothesis postulates a reduction in
      the ratio of total added IFN to residual active IFN molecules, such as a low
      affinity antibody might exhibit. Analyses of data of the neutralization of IFN
      alpha and IFN-beta are presented, employing human polyclonal antibodies and
      murine monoclonal antibodies (mAb). The theoretical constructs of Kawade are
      extended in the Appendix and correlated with new experimental data in the text.
      The data clearly indicate that the low-antibody affinity, constant proportion
      hypothesis, rather than the high-antibody affinity, fixed amount hypothesis, is
      applicable, if the bioassay is sensitive to IFN. The findings presented here and
      in the following paper (pp. 743-755, this issue) taken together provide the basis
      for a standardized method of expression of neutralizing potency and substantiate
      the earlier operational 10/1 LU/ml approach recommended by the World Health
      Organization. The accompanying paper relates neutralization results to the
      sensitivity of the bioassay to IFN and describes the rationale for a recommended
      unit of antibody neutralization.

PMID- 11576468
TI  - The neutralization of interferons by antibody. II. Neutralizing antibody unitage
      and its relationship to bioassay sensitivity: the tenfold reduction unit.
AB  - The importance of establishing a common method of reporting neutralizing antibody
      levels is emphasized by the fact that patients injected repeatedly with a human
      interferon (HuIFN) may develop such antibodies that can abrogate the beneficial
      effects of the treatment. The earlier experimental and theoretical constructs of
      Kawade led to certain recommendations by the World Health Organization (WHO)
      concerning the methodology of neutralization tests and how to report the
      resultant data. A WHO international collaborative study on two human sera with
      antibodies against HuIFN-alpha and HuIFN-beta provided the opportunity not only
      to test the theoretical concepts concerning the neutralization reaction with data
      obtained in different bioassay systems in different laboratories but also to
      obtain enough data points for statistical evaluation with bioassays having a
      great range of sensitivity to IFN. The analyses substantiate and extend the
      original conclusions of Kawade that the neutralization follows the reaction mode
      of low-affinity antibody, in accord with the constant proportion hypothesis by
      which antibody reduces IFN activity in a set ratio of added/residual biologically
      active IFN, a consequence of the low molar concentration of free IFN at the
      neutralization end point. The present results support the recommendation that the
      preferred way to state the index of neutralization of antibodies is a titer (t),
      calculated by the formula t = f(n - 1)/9, where f is the reciprocal of the
      antibody dilution achieving the end point, and n is the IFN concentration
      measured in that day's titration. The tenfold reduction unit (TRU) of
      neutralization is proposed for use in expressing the quantity, or unitage, of IFN
      neutralizing antibody. The utility of its application is explained. The use of
      the index of neutralization described and the proposed derivative term of
      antibody unitage, TRU, should help make the results from different laboratories
      employing different bioassay systems more readily comparable and interpretable,
      provided the bioassays are sufficiently sensitive to IFN.

PMID- 11576469
TI  - Hypoxic upregulation of TNF receptor type 2 expression involves NF-IL-6 and is
      independent of HIF-1 or HIF-2.
AB  - Tumor necrosis factor (TNF) exerts its biologic activity via two distinct
      membrane receptors, TNF receptor type 1 (p55TNFR) and TNF receptor type 2
      (p75TNFR). Whereas the p55TNFR gene is rather constitutively expressed,
      transcription of p75TNFR is strongly modulated by a number of stimulatory agents.
      Experimental evidence suggested the involvement of p75TNFR in endothelial cell
      activation. Therefore, we have tested the transcriptional activity of p75TNFR
      under conditions of hypoxia and reoxygenation. Northern blot analysis revealed
      that p75TNFR mRNA is upregulated in NIH3T3 cells under hypoxia and reoxygenation.
      This observation directly originates from transcriptional activation of the
      p75TNFR gene, as shown by reporter gene analysis. Cotransfection experiments
      clearly showed that the transcriptional induction of the p75TNFR gene is
      independent of the hypoxia-induced factors, HIF-1alpha and HIF-2alpha. Using
      deletion mutants of the 5'-flanking region of the p75TNFR gene, we were able to
      identify a putative DNA binding site for the transcription factor nuclear factor
      interleukin-6 (NF-IL-6) to be responsible for the transcriptional upregulation of
      the p75TNFR gene under conditions of hypoxia and reoxygenation.

PMID- 11576470
TI  - Myeloid dendritic cells stimulate both Th1 and Th2 immune responses depending on
      the nature of the antigen.
AB  - It has been shown that different types of pathogens induce different immune
      responses. Recovery from intracellular bacterial and viral infection is dependent
      on the secretion of Th1 cytokines, such as interferon-gamma (IFN-gamma), and on
      the generation of cytotoxic T cells. In contrast, responses to some parasitic
      invaders are of the Th2 type, characterized by secretion of interleukin-4 (IL-4).
      At present, it is not clear what directs this choice, and the most prevalent
      hypotheses are based on the dendritic cells (DC). In this work, we studied the
      immune responses generated in mice to a number of antigens, both replicating and
      nonreplicating, using bone marrow-derived DC as vehicles for immunization. We
      demonstrate that DC infected with influenza virus prime for a pure Th1 response
      in vivo devoid of IL-4 induction. This immune response correlates with the
      induction of DC maturation by the virus. In contrast, nonreplicating antigens,
      such as fetal bovine serum (FBS), beta-galactosidase, or inactivated influenza
      virus, do not mature the DC and prime for responses characterized by the
      secretion of large amounts of IL-4. These data support the hypothesis that
      myeloid DC are capable of eliciting both types of responses depending on the
      nature of the antigen.

PMID- 11576471
TI  - Telemedicine and developing countries--successful implementation will require a
      shared approach.
AB  - Telemedicine is often proposed as a solution to certain health-care problems in
      the developing world. There seems to be little published experience on which to
      make judgements. A literature search revealed 39 articles, of which only two
      related to any kind of direct clinical work; most of them were review articles or
      editorials. The majority of the work reported was educational in nature, and
      there has been little clinical experience. It seems probable that telemedicine
      can help with the education of health-care workers and patients; it seems likely
      that it could bring major benefits to the organization of health-care. Without
      proper trials, it will be impossible to determine the place of health-care in the
      developing world. Trials are the only way in which rational decisions can
      ultimately be reached regarding whether scarce resources should be devoted to
      telemedicine in developing countries, or whether they should be employed in more
      conventional health-care measures whose outcomes are known to be cost-effective.

PMID- 11576472
TI  - The effect of resolution, compression, colour depth and display modality on the
      accuracy of accident and emergency telemedicine.
AB  - There are no current recommendations regarding the minimum technical
      specification for realtime telemedicine consultation in accident and emergency (A
      and E) practice. We assessed the effect of image resolution, compression, colour
      depth and display modality on perceived image quality and telediagnosis. Test
      sets of digitized radiographs and clinical images were subjected to a series of
      standardized manipulations and the resulting output files were evaluated by an
      expert panel using image scoring and receiver operating characteristic (ROC)
      analysis. For telemedicine in A and E work, the minimum technical specification
      should be regarded as images containing at least 250,000 pixels, compressed at up
      to JPEG 50 (or GIF for colour images) and displayed on a high-resolution computer
      monitor. These specifications resulted in average file sizes of 17 kByte for
      digital images and 9 kByte for radiographs.

PMID- 11576473
TI  - The use of telepsychiatry in the brief counselling of non-psychotic patients from
      an inner-London general practice.
AB  - Brief counselling of 13 non-psychotic patients was carried out using an
      interactive television link, in order to assess patient satisfaction with this
      technique. Informed consent was obtained from all patients before the
      videoconferencing sessions, which were conducted at 128 kbit/s. Over the four
      month study period, 11 men and two women participated in a total of 29 sessions.
      A total of 28 questionnaires were completed. After the sessions, 93% of patients
      agreed that they would like to use this medium for communication again, 75%
      stated that they were able to see everything that they needed to see and 86%
      agreed that they were able to hear everything they needed to hear. Overall, these
      findings indicate that patients were happy with the standard of care they
      received.

PMID- 11576474
TI  - Telehealth consultations in rheumatology: cost-effectiveness and user
      satisfaction.
AB  - We conducted a feasibility study to assess user satisfaction with and the cost
      effectiveness of a rheumatology telehealth clinic in northern Alberta. Six
      telehealth clinics were organized between a rural health centre and the
      specialist rheumatology centre, which was about a 4 h drive away. Fifty-two new
      patients were seen. Their median age was 54 years (range 7-81 years). After the
      teleconsultation, no patient required a conventional face-to-face consultation.
      Overall, patients agreed that the teleconsultation met their needs and that the
      care they received was as good as conventional care. The physicians involved in
      the study thought the process practical and effective. The total costs of service
      delivery would be equal for teleconsultation and for traditional consultation at
      a workload of 247 consultations a year.

PMID- 11576475
TI  - The potential of telemedicine: barriers, incentives and possibilities in the
      implementation phase.
AB  - Between 1998 and 1999, the Swedish Institute for Health Services Development
      (Spri) evaluated three applications in which specialist competence was being
      accessed via telemedicine. The results indicated that these kinds of application
      can be cost-effective in an organization well adapted to new technology and that
      telemedicine can improve continuity of care for patients. However, the new
      technology was seldom supported by the old organization and better education and
      technical support are needed. In a study called 'Incentives and Implementation',
      the Federation of Swedish County Councils interviewed people in Swedish health
      care with a lot of experience of telemedicine. The interviewees agreed that
      telemedicine was likely to affect the whole structure of health-care. Peripheral
      competence was expected to increase and referral patterns to change, as well as
      the functions of the personnel and the hospitals. New working conditions and
      methods of work were expected to be made possible by telemedicine and health-care
      was expected to become more process oriented, partly because patients are likely
      to be more demanding and better informed. To be able to utilize this potential,
      health-care managers will have to show more interest in and commitment to
      telemedicine. Old organizational patterns must be called into question and be
      developed along with information technology and telemedicine. It is also
      important to give priority to training in telemedicine for physicians and nurses.

PMID- 11576476
TI  - Effect of wavelet compression on data transmission in a multipurpose wireless
      telemedicine system.
AB  - We have developed a novel emergency telemedicine system which allows the
      transmission of physiological data (electrocardiogram, oximetry, blood pressure
      and temperature) and still images of the patient. The transmission is performed
      through wireless links using either GSM mobile phones or satellite. Because of
      the low bandwidth available through these links, data compression is required to
      allow realtime transmission of electrocardiographic (ECG) data. A new integrated
      design approach for an optimal zonal wavelet compression (OZWC) method was
      implemented for the ECG data. The performance of the mobile system with
      compressed ECG data segments was evaluated in terms of the percentage root-mean
      square difference and visual inspection. The optimum wavelet algorithm achieved a
      maximum compression ratio of 18:1 with low distortion.

PMID- 11576477
TI  - Telemedicine options appraisal for a health district--a strategic clinical and
      business case.
AB  - A clinical and business plan examined five areas in which telemedicine could be
      introduced to support the strategic objectives of a large health authority:
      coronary heart disease; links between community hospitals and local care centres
      and acute hospitals; store-and-forward consultations; care in the community; and
      mental health. The plan identified substantial clinical, organizational and
      economic potential benefits, which were greatest when a radical re-engineering of
      the service was envisaged. Similar studies in other health districts would help
      to test these conclusions and inform future health service planning.

PMID- 11576478
TI  - Utilization and practical aspects of tele-ophthalmology between South Africa and
      the UK.
AB  - A tele-ophthalmology service was established between a regional hospital in South
      Africa and a specialist eye hospital in the UK. The aim of the service was to
      provide secondary specialist advice in the diagnosis and treatment of difficult
      ophthalmology cases in South Africa. Over 12 months, the South African medical
      officers saw 16,458 ophthalmology patients and would have liked a second opinion
      in 5.7% of these cases. Case discussions conducted by videoconferencing at 384
      kbit/s were carried out in 0.5% of cases. No significant connection problems were
      experienced during the 12-month study period. On 4% of occasions, the case
      discussions were conducted at a bandwidth of 256 kbit/s, but this did not affect
      the quality of the still images. The South African medical officers valued the
      educational benefits gained from the case discussions with the UK specialists.

PMID- 11576479
TI  - A simulation model for analysing patient activity in dermatology.
AB  - We developed a general model to assess patient activity within the primary and
      secondary health-care sectors following a dermatology outpatient consultation.
      Based on observed variables from the UK teledermatology trial, the model showed
      that up to 11 doctor-patient interactions occurred before a patient was
      ultimately discharged from care. In a cohort of 1000 patients, the average number
      of health-care visits was 2.4 (range 1-11). Simulation analysis suggested that
      the most important parameter affecting the total number of doctor-patient
      interactions is patient discharge from care following the initial consultation.
      This implies that resources should be concentrated in this area. The introduction
      of teledermatology (either realtime or store and forward) changes the values of
      the model parameters. The model provides a quantitative tool for planning the
      future provision of dermatology health-care.

PMID- 11576480
TI  - Tele-ophthalmology for the treatment in primary care of disorders in the anterior
      part of the eye.
AB  - Desktop videoconferencing at 384 kbit/s was used for a trial of tele
      ophthalmology consultations between a general practitioner (GP) and an
      experienced ophthalmologist. Forty-two consecutive patients from St Erik's Eye
      Hospital emergency ward with disorders in the anterior part of the eye were
      examined. There was an excellent correlation between the diagnoses made with
      telemedicine support and those made by the ophthalmologist directly.
      Subsequently, the GP made 121 eye examinations in two years out of a total of
      approximately 300-400 examinations at the health-care centre. In the first year
      the GP examined and treated 45-50% of the cases on his own and 30-50% with
      telemedicine support. In the second year he treated 55-80% of the cases on his
      own and 5-35% with telemedicine support. Tele-ophthalmology in primary care
      appears to be reliable and is likely to be valuable in rural areas, where the
      distance to an ophthalmologist can be a significant obstacle to satisfactory
      diagnosis and treatment.

PMID- 11576481
TI  - Early experience with transmission of data from moving ambulances to improve the
      care of patients with myocardial infarction.
AB  - We conducted a feasibility study of a mobile unit capable of recording a 12-lead
      electrocardiogram (ECG) and transmitting it to a receiving hospital workstation.
      Two ambulances were equipped with the mobile unit and the ECGs recorded were
      compared with standard ECGs recorded on the hospital ward after admission. In six
      months, 62 patients participated in the study. The ambulance crew transmitted
      messages to the coronary care unit for 56 patients. Thirty-five patients were
      directed to the coronary care unit, four were directed to the emergency
      department as no beds were available and then transferred to the coronary care
      unit later, and the remaining 23 were directed to the emergency department.
      Comparative hospital and mobile ECGs were available for 31 patients. Although the
      mobile unit recorded smaller R- and S-wave deflections than on the standard
      hospital ECGs, the medical and nursing staff were able to differentiate between
      normal and abnormal tracings. The mobile unit may be useful to triage patients
      with chest pain before they reach hospital.

PMID- 11576482
TI  - Subspecialty adnexal ophthalmological examination using telemedicine.
AB  - We studied the clinical outcome of examination of a group of patients with
      adnexal (eyelid and orbit) conditions. Seventeen patients with adnexal problems
      were assessed by an ophthalmologist at a distance using telemedicine, and then
      subsequently by an ophthalmologist in a face-to-face consultation. Measurements
      such as palpebral aperture, levator muscle function and eyelid skin crease
      position were recorded. The clinical outcomes from both consultations were
      recorded independently by the consultants and then compared. The study showed
      that certain adnexal conditions, such as congenital and involutional ptosis,
      could be accurately assessed using telemedicine, but that other conditions, such
      as socket problems in patients who had a previous enucleation or those with non
      specific ocular pain with less clear-cut features, were better assessed in a face
      to-face consultation. Overall, teleconsultations appeared to be suitable for the
      assessment of uncomplicated ptosis but not for less well defined conditions.
      Other factors, such as family dynamics and language problems, also limited the
      usefulness of the technique.

PMID- 11576484
TI  - The provision of a telepsychology service to Shetland: client and therapist
      satisfaction and the ability to develop a therapeutic alliance.
AB  - We conducted a pilot study to assess the feasibility and acceptability of
      videoconferencing as a means of providing a clinical psychology service in the
      Shetland Islands. A general practitioner was equipped with a desktop PC-based
      system connected to a mainland hospital videoconferencing system by ISDN at 128
      kbit/s. Qualitative methods were used to assess user satisfaction, the ability to
      form a therapeutic relationship and client improvement. Over one year, 10
      patients (eight female, two male) participated in the videoconferencing therapy
      sessions. The psychologist and all but one of the clients were highly satisfied
      with the videoconferencing therapy sessions. The clients were able to develop a
      positive therapeutic relationship with the psychologist and all reported some
      improvement from therapy. The results showed that videoconferencing is a feasible
      and acceptable means of providing therapy to patients in remote areas.

PMID- 11576483
TI  - Hospital-managed advanced care of children in their homes.
AB  - A hospital-managed project for the advanced care of children in their homes
      (SABH) has been established in Sweden. The aim was to provide an alternative to
      inpatient paediatric care by providing hospital-at-home care to stable infants
      and children using mobile units based on advanced information and communication
      technology. The Karolinska Hospital children's ward and emergency room referred
      children to SABH care. A medical care plan was drawn up by the physicians and
      nurses responsible for the patient while in hospital, in conjunction with the
      parents and the patient. In one year, 350 episodes of care requiring 3000 bed
      days were managed by SABH in the children's homes rather than at hospital. Forty
      two per cent of the patients were aged less than one year, 41% were between one
      and six years old, and 17% were older than six years. SABH care was at least 30%
      cheaper than conventional hospital care and patient satisfaction with the service
      was high. At the conclusion of the two-year project, the SABH became a permanent
      unit at the Karolinska Hospital.

PMID- 11576485
TI  - Telemedicine in Greenland--the creation of an evaluation plan.
AB  - Implementation of telemedicine in Greenland is a continuing process based on a
      plan of operation for the years 1999-2002. In this context, a plan of evaluation
      was designed as a health technology assessment in interdisciplinary cooperation
      between the Telemedicine Team of Greenland and the Norwegian Centre of
      Telemedicine in Tromso. The geography of Greenland, the financial situation and
      the shortage of medical staff influenced the way in which the evaluation was
      designed. This has implications for the extent to which the results may be
      generalized.

PMID- 11576486
TI  - Avoiding artificiality in teleconsultations.
AB  - The ideal videoconferencing environment would produce the minimum feeling of
      artificiality for its users. We assessed nurse and patient perceptions of
      artificiality by varying the technical and operational procedures for
      telemedicine in a minor injuries unit. Twenty-five patients and eight emergency
      nurse practitioners (ENPs) participated in simulated teleconsultations under a
      variety of different conditions and completed a Likert-scale survey. There was a
      close correlation between the ENPs' ratings and the patients' ratings for the
      various factors (r > 0.99). In relation to technical factors, a flicker-free
      television screen and the user being seated close to the screen were preferred.
      Similarly, in relation to operational procedures, an initial explanation of
      telemedicine, introductions and adequate preparation were also preferred. The
      study suggests that careful attention to technical specifications and operational
      procedures can reduce the perceived artificiality of teleconsultations.

PMID- 11576487
TI  - Using telemedicine for distance education.
AB  - We assessed the use of videoconferencing as an educational tool for students and
      emergency nurse practitioners based at a minor injuries unit. Nineteen teaching
      sessions were conducted by videoconferencing, followed by a debriefing session in
      which the participants made observations about their educational experience. The
      participants observed that the experience was rewarding. The success of the
      teaching session depended on group size: an upper limit of six is recommended.
      The teaching sessions encouraged debate, independent thinking and peer
      communication.

PMID- 11576488
TI  - Patient satisfaction with store-and-forward teledermatology.
AB  - We assessed patient satisfaction with a nurse-led store-and-forward
      teledermatology service in Manchester. A teledermatology nurse obtained the
      patient's history, took digital photographs of the patient's skin lesion and then
      sent the information to a hospital dermatologist, who responded with management
      advice the following week. Of 141 patients who attended their teledermatology
      appointment, 123 (50 male, 73 female) completed the study questionnaire (87%).
      The average age of respondents was 42 years (SD 17, range 18-90 years). Ninety
      three per cent reported that they were happy with the teleconsultation while 86%
      reported that it was more convenient than going to the outpatient clinic. Forty
      per cent agreed that they would feel more comfortable seeing the dermatologist in
      person while only 58% were comfortable with not speaking to the dermatologist
      about their skin condition. The absence of interaction with the dermatologist and
      the delay in receiving management advice may have contributed to the somewhat low
      satisfaction rates.

PMID- 11576489
TI  - Clinical outcomes in a prison telepsychiatry clinic.
AB  - The effectiveness of a prison telepsychiatry service was evaluated from a user
      perspective. Forty-five inmates (41 male, 4 female) completed the Symptom Rating
      Checklist-90-Revised (SCL-90-R) on three occasions, once before the
      teleconsultation and twice during treatment. The psychiatrist completed the
      Clinical Global Impression Scale--Severity Index (CGI) after each
      teleconsultation. Forty-nine per cent of inmates were aged under 30 years, 24%
      were aged between 30 and 39 years, while 27% were aged over 40 years. The
      inmates' mean SCL-90-R scores decreased over time, indicating less psychiatric
      distress. The psychiatrist reported patient improvement over time as assessed by
      the CGI. Telepsychiatry is an effective means of delivering mental health
      services to the prison population.

PMID- 11576490
TI  - The potential for telemedicine to improve coronary heart disease services.
AB  - The potential of telemedicine to improve services for patients suffering from
      coronary heart disease (CHD) was explored. Key issues surrounding the delivery of
      CHD services in London were identified, such as a shortage of skilled staff, the
      need for appropriate patient information and problems with waiting times,
      particularly for diagnostic test results. Telemedicine has the potential to
      improve service delivery in each of these areas. It is unlikely that some of the
      targets for CHD service delivery set out by the Department of Health's National
      Service Frameworks can be met without the use of telemedicine.

PMID- 11576491
TI  - Store-and-forward teleneurology in developing countries.
AB  - We assessed the feasibility of a store-and-forward email teleneurology service
      between a UK neurologist and a rehabilitation hospital in Bangladesh. Over 12
      months, email advice was requested for 12 patients (mean age 43 years, range 15
      57 years). Each patient generated an average of 5.2 email messages. Eight cases
      were considered complicated by the neurologist, who would have preferred a video
      link consultation for these. The referring doctor found the neurologist's advice
      beneficial in 75% of the complex cases and in all of the more straightforward
      cases. Patient care was changed in 50% of the cases as a result of the specialist
      advice and one patient transfer out of the country was avoided. Store-and-forward
      teleneurology is effective for delivering expert neurological advice.

PMID- 11576492
TI  - A knowledge-based multimedia telecare system to improve the provision of formal
      and informal care for the elderly and disabled.
AB  - We have developed a knowledge-based multimedia telecare system, based on a
      multimedia PC connected by ISDN at 128 kbit/s. The user display is a television.
      Multimedia material is accessed through a browser-based interface. A remote
      control handset is used as the main means of interaction, to ensure ease of use
      and overcome any initial reservations resulting from 'technophobia' on the part
      of the informal carer. The system was used in 13 family homes and four
      professional sites in Northern Ireland. The evaluations produced positive
      comments from the informal carers. There are plans to expand the use of the
      system.

PMID- 11576493
TI  - Experience with a low-cost telemedicine system in three developing countries.
AB  - The Swinfen Charitable Trust was established in 1998 with the aim of helping the
      poor, sick and disabled in the developing world. It does this by setting up
      simple telemedicine links based on email to support doctors in isolated
      hospitals. The first telemedicine link was established to support the lone
      orthopaedic surgeon at the Centre for the Rehabilitation of the Paralysed (CRP)
      in Savar, near Dhaka in Bangladesh, in July 1999. An evaluation of the 27
      referrals made during the first year of operation showed that the telemedical
      advice had been useful and cost-effective. Based on the success of the Bangladesh
      project, the Swinfen Charitable Trust supplied digital cameras and tripods to
      more hospitals in other developing countries. These are Patan Hospital in Nepal
      (March 2000), Gizo Hospital in the Solomon Islands (March 2000), Helena Goldie
      Hospital on New Georgia in the Solomon Islands (September 2000) and LAMB Hospital
      in Bangladesh (September 2000).

PMID- 11576494
TI  - The development of a telemedicine system for a centralized maxillofacial unit
      serving four towns.
AB  - Following the amalgamation on one site of inpatient oral and maxillofacial
      surgical (OMFS) services serving four towns, patients attending accident and
      emergency (A and E) departments in Bolton, Burnley and Bury who required
      specialist OMFS care were transferred to Blackburn. This sometimes led to
      inappropriate transfer, with inconvenience for patients, sub-standard care and
      wasted resources. To reduce these problems, a videoconferencing system was
      established, linking the A and E departments of three peripheral hospitals to the
      central site. This allowed realtime visualization of patients and their
      radiographs, discussion between clinicians and transfer of a summary data-sheet.
      The aim was to improve remote diagnosis and to deliver a cost-effective, high
      quality specialist service. In the first 12 months, there were an average of 25
      remote consultations per month, with favourable feedback from both patients and
      clinicians.

PMID- 11576495
TI  - Transmission trials with a support system for the treatment of cardiac arrest
      outside hospital.
AB  - A mobile electrocardiogram (ECG) transmission system was developed which could
      transmit single-lead ECG data via GSM mobile telephony. Ambulance transmission
      trials comprised a total of 72 communications, of which 94% were successful. The
      system was able to redial up to a predetermined number of times until the GSM
      call was re-established (during the trials this value was set to five). The
      average number of GSM call tries was 1.3 per connection. The mean time required
      to establish a connection was 45 s; the minimum was 34 s, when only one attempt
      was needed to establish a GSM call. The average duration of ECG transmission
      between communication breakdowns was 5 min 12 s. When a link breakdown occurred,
      the user had to wait for an average of only 42 s to continue monitoring the
      signal.

PMID- 11576496
TI  - Cost implications of outpatient teleneurology.
AB  - A randomized controlled trial was conducted to compare the costs of realtime
      teleneurology with the cost of conventional neurological care. Two district
      hospitals in Northern Ireland were equipped with videoconferencing units and were
      connected to the regional neurological centre by ISDN at 384 kbit/s. Of 168
      patients randomized to the study, 141 kept their appointments (76 male, 65
      female). Sixty-five patients were randomized to a conventional consultation while
      76 were randomized to a teleconsultation. The average age was 44 years of those
      seen conventionally and 42 years of those seen by telemedicine. The groups had
      similar diagnoses. The telemedicine group required more investigations and
      reviews than the conventional group. The average cost of the conventional
      consultation was 49 pounds sterling compared with 72 pounds sterling for the
      teleconsultation. Realtime teleneurology was not as cost-effective as
      conventional care.

PMID- 11576497
TI  - Modelling home televisiting services using systems dynamic theory.
AB  - A quantitative model was developed to study the provision of a home televisiting
      service. Systems dynamic theory was used to describe the relationships between
      quality of care, accessibility and cost-effectiveness. Input information was
      gathered from the telemedicine literature, as well as from over 75 sessions of a
      televisiting service provided by the Severo Ochoa Hospital to 18 housebound
      patients from three different medical specialties. The model allowed the Severo
      Ochoa Hospital to estimate the equipment needed to support increased medical
      contacts for intensive cardiac and other patients.

PMID- 11576498
TI  - Implementation and evaluation of telemedicine for remote health-care--the
      European Northern Periphery Programme Project.
AB  - We evaluated the provision of telemedicine services based on information
      technology in four northern European countries. Improved communication and access
      to specialist care was reported, as well as cost reductions in certain areas.

PMID- 11576499
TI  - The development of a new model for community telemedicine services.
AB  - Two trials of a telemedicine monitoring system were conducted in the UK. The
      SAFE21 system records the patient's physiological data, which are transmitted via
      a modem to the health service provider. The first trial was conducted on nine
      muscular dystrophy patients under 18 years of age. Eight of the patients felt
      that the monitoring system was reliable and were happy with it, as it avoided the
      need to go to hospital for monitoring. The second trial was carried out on 14
      patients suffering from respiratory illness. Thirteen of these patients felt that
      the service was useful and 12 reported satisfaction with the system. The SAFE21
      telemedicine monitoring system appears to be an acceptable means of delivering
      care.

PMID- 11576500
TI  - Patient and physician satisfaction with telemedicine for monitoring vital signs.
AB  - We evaluated user satisfaction with realtime telemedicine for monitoring vital
      signs. Over eight weeks, 20 patients and 12 residents in family medicine
      participated in the study. At the end of the study, the patients and doctors
      completed a questionnaire detailing satisfaction with the service. Responses were
      obtained from 18 of the 20 patients and were generally positive: 61% were
      comfortable using the system and 94% did not believe that the technology had a
      negative effect on their relationship with the health-care provider. Eleven
      physician responses were obtained. Physicians were more uncertain about the
      benefits of the service: only 45% felt that telemedicine could adequately assess
      patients, although 82% felt that telemedicine would be an important part of
      primary-care services. From a user perspective, our study showed that patients
      were more satisfied with the telemedicine service than were doctors.

PMID- 11576501
TI  - Teleradiology in Croatia.
AB  - A teleradiology system connecting 35 workstations in 27 hospitals was established
      in Croatia. In two years of operation, 2071 consultations were conducted using
      the system at an average rate of four neurosurgical teleconsultations per day.
      Eighty patients required urgent transfer to the tertiary hospital and 181
      required non-urgent transfer. An additional 181 patients remained in their local
      hospital and were treated under the supervision of the tertiary hospital. The
      avoidance of unnecessary patient transfer led to significant cost savings.

PMID- 11576502
TI  - The use of a new continuous wireless cardiorespiratory telemonitoring system by
      elderly patients at home.
AB  - The diagnosis and management of increasing numbers of patients with chronic
      diseases in the community require new technologies and strategies of care. We
      have used a new wireless cardiorespiratory telemonitoring system to monitor 14
      elderly patients with a variety of chronic diseases at home. The
      electrocardiogram (ECG), heart rate and variability, and breathing were recorded
      on two separate occasions for 24 h. There was no difference in the data recorded
      when a research nurse applied the monitoring system and when the patients applied
      it themselves. The ECG and heart rate were recorded for 98% of the monitored
      time, and the frequency and periodicities of breathing were recorded for 74% and
      61% of sleep and rest time by visual and automatic analysis, respectively. The
      results show that 24 h activity and cardiorespiratory telemonitoring can be
      performed by elderly patients at home. Significant unsuspected abnormalities of
      breathing and heart rhythm, amenable to treatment, were also detected.

PMID- 11576518
TI  - Introduction.

PMID- 11576519
TI  - Pathophysiologic mechanisms of postprandial hyperglycemia.
AB  - The role of postprandial hyperglycemia in the etiology of diabetes-related
      complications and outcomes, although still being elucidated, is greater than
      previously thought. Acute glucose elevations after meal ingestion are associated
      with a variety of glucose-mediated tissue defects-oxidative stress, glycation,
      and advanced glycation end product formation-which have far-reaching structural
      and functional consequences for virtually every human organ system. Lowering
      glycosylated hemoglobin to levels that prevent or delay these complications can
      be achieved only by reducing both postprandial and fasting plasma glucose levels.
      The alpha-glucosidase inhibitors (acarbose, voglibose, miglitol) have been
      effective in delaying the digestion and absorption of carbohydrates, thus
      diminishing the postprandial surge in blood glucose levels without loss of
      calories. However, greater emphasis needs to be placed on the measurement of
      postprandial glycemia, so that readings can be used to guide treatment.

PMID- 11576520
TI  - Postprandial dyslipidemia: an atherogenic disorder common in patients with
      diabetes mellitus.
AB  - The increased risk of coronary artery disease among patients with diabetes
      mellitus is attributable, in part, to specific disorders of lipoprotein
      metabolism that are common in this population. These include disordered
      metabolism of very-low-density lipoprotein and/or chylomicrons that may be
      proatherogenic. Elevated postprandial triglycerides, peak postprandial
      triglyceridemia, and late postprandial triglyceride levels have been associated
      in clinical trials with both early coronary artery and carotid artery
      atherosclerosis for persons with normal lipid profiles and those with mild-to
      moderate hyperlipidemia, independently of established risk factors. If
      hyperlipidemia cannot be managed through better glycemic control, diet, and
      exercise, then hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors, fibric acid derivatives, and omega-3 fatty acids are safe and
      effective lipid-altering agents that can be used to correct these disorders.

PMID- 11576521
TI  - Impaired glucose tolerance as a disease.
AB  - Current criteria for diagnosing diabetes, based on fasting plasma glucose levels
      during administration of the oral glucose tolerance test (OGTT), are poorly
      sensitive and are only modestly predictive of microvascular risk. The period
      after administration of OGTT is far more predictive and more closely resembles
      the postprandial state where microvascular risk is elevated. However, persons who
      do not yet exhibit symptoms of diabetes may nonetheless have impaired glucose
      tolerance or dysglycemia, whereby macrovascular disease can develop at a glucose
      level lower than the threshold for microvascular disease and can progress in a
      graded fashion. This article reviews the factors that may cause dysglycemia
      (including insulin resistance and obesity) and how diet, blood pressure control,
      and the use of statins or glycemic/insulin sensitizing may reduce cardiovascular
      risk in this prediabetic population.

PMID- 11576522
TI  - Effect of the postprandial state on nontraditional risk factors.
AB  - Hyperglycemia is the cause of chronic microvascular complications in diabetes.
      Increased macrovascular disease occurring in diabetes is multifactorial, with
      hyperglycemia being only 1 of the factors responsible. A major deficiency in our
      understanding of the role of hyperglycemia in the pathogenesis of chronic
      diabetic complications is the contribution made by exaggerated postprandial
      glycemic excursions, in contrast to that made by chronic fasting hyperglycemia.
      Hyperglycemia is thought to cause chronic diabetic complications through > or = 1
      of the following biochemical mechanisms: (1) an exaggerated polyol pathway, (2)
      protein glycation and the formation of advanced glycation end products, (3)
      excessive activation of protein kinase C (PKC) isoenzymes in vascular and
      mesangial cells, and (4) greater oxidative stress. The focus of this article is
      how postprandial hyperglycemia and glucose excursions might specifically activate
      > or = 1 of these mechanisms and how they might contribute to the development of
      the chronic complications of diabetes by causing endothelial dysfunction, a
      procoagulant state, carbonyl stress, and/or vascular and oxidative effects
      secondary to PKC activation.

PMID- 11576523
TI  - Controlling postprandial hyperglycemia.
AB  - A growing body of evidence indicates that measurements of postprandial glucose
      levels, in combination with glycosylated hemoglobin, are a more accurate
      predictor of metabolic abnormality than fasting or preprandial glucose levels for
      individuals with type 2 diabetes. Early identification of elevated postprandial
      blood glucose levels is an important step in predicting the onset of
      microvascular and macrovascular complications that can progress to full
      symptomatic diabetes. This article summarizes the research conducted to date on
      the diagnostic import of postprandial glucose and the parameters established for
      judging the need for treatment. When individuals cannot reach target glucose
      levels through diet and exercise, medical treatment is necessary. The article
      reviews a range of treatment options, including insulin secretagogues, insulin
      sensitizers, antiabsorptive agents, weight reduction agents, and insulin and
      combination medical therapy.

PMID- 11576524
TI  - Postprandial hyperglycemia: implications for practice.
AB  - Despite the growing consensus that postprandial glucose levels provide a more
      accurate and valuable early marker of diabetes symptoms than fasting plasma
      glucose, the ability to forestall diabetic complications by managing postprandial
      hyperglycemia has not been proved. Patients who are not considered to have
      diabetes mellitus may have impaired glucose tolerance (and increased risk for
      developing cardiovascular disease), and targeting nonfasting glucose can reduce
      insulin requirements for patients with insulin-dependent diabetes mellitus (type
      1 diabetes mellitus). The challenge now is to determine what fasting glucose
      levels merit intervention, when and how they should be determined, and who should
      measure them. After outlining the discrepancies and lack of consensus between
      measurement guidelines developed by different professional organizations, the
      author then reviews options for treating postprandial hyperglycemia, including
      prepackaged meals, alpha-glucosidase inhibitors, acarbose therapy, and fast
      acting insulin preparations.

PMID- 11576525
TI  - Chaperonins--keeping a lid on folding proteins.
AB  - Two classes of chaperonins are known in all groups of organisms to participate in
      the folding of newly synthesized proteins. Whereas bacterial type I chaperonins
      use a reversibly binding cofactor to temporarily sequester folding substrate
      proteins within the cylindrical chaperonin cavity, type II chaperonins in archaea
      and the eukaryotic cytosol appear to have evolved a built-in lid for this
      purpose. Not entirely surprisingly, this has consequences for the folding modes
      of the two types of chaperonins.

PMID- 11576526
TI  - Insulin antagonizes AMP-activated protein kinase activation by ischemia or anoxia
      in rat hearts, without affecting total adenine nucleotides.
AB  - AMP-activated protein kinase (AMPK) is known to be activated by phosphorylation
      on Thr172 in response to an increased AMP/ATP ratio. We report here that such an
      activation indeed occurred in anaerobic rat hearts and that it was antagonized
      (40-50%) when the hearts were pre-treated with 100 nM insulin. The effect of
      insulin (1) was blocked by wortmannin, an inhibitor of phosphatidylinositol-3
      kinase; (2) only occurred when insulin was added before anoxia, suggesting a
      hierarchical control; (3) resulted in a decreased phosphorylation state of Thr172
      in AMPK and (4) was unrelated to changes in the AMP/ATP ratio. This is the first
      demonstration that AMPK activity could be changed without a detectable change in
      the AMP/ATP ratio of the cardiac cell.

PMID- 11576527
TI  - The central plug in the reconstituted undecameric c cylinder of a bacterial ATP
      synthase consists of phospholipids.
AB  - The isolated rotor cylinder of the ATP synthase from Ilyobacter tartaricus was
      reconstituted into two-dimensional crystalline arrays. Atomic force microscopy
      imaging indicated a central cavity on one side of the rotor and a central plug
      protruding from the other side. Upon incubation with phospholipase C, the plug
      disappeared, but the appearance of the surrounding c subunit oligomer was not
      affected. This indicates that the plug consists of phospholipids. As the
      detergent-purified c cylinder is completely devoid of phospholipids, these are
      incorporated into the central hole from one side of the cylinder during the
      reconstitution procedure.

PMID- 11576528
TI  - Inhibition of lipoprotein-associated phospholipase A2 diminishes the death
      inducing effects of oxidised LDL on human monocyte-macrophages.
AB  - The death of macrophages contributes to atheroma formation. Oxidation renders low
      density lipoprotein (LDL) cytotoxic to human monocyte-macrophages. Lipoprotein
      associated phospholipase A2 (Lp-PLA2), also termed platelet-activating factor
      acetylhydrolase, hydrolyses oxidised phospholipids. Inhibition of Lp-PLA2 by
      diisopropyl fluorophosphate or Pefabloc (broad-spectrum serine esterase/protease
      inhibitors), or SB222657 (a specific inhibitor of Lp-PLA2) did not prevent LDL
      oxidation, but diminished the ensuing toxicity and apoptosis induction when the
      LDL was oxidised, and inhibited the rise in lysophosphatidylcholine levels that
      occurred in the inhibitors' absence. Hydrolysis products of oxidised
      phospholipids thus account for over a third of the cytotoxic and apoptosis
      inducing effects of oxidised LDL on macrophages.

PMID- 11576529
TI  - The site of production of superoxide radical in mitochondrial Complex I is not a
      bound ubisemiquinone but presumably iron-sulfur cluster N2.
AB  - The mitochondrial respiratory chain is a powerful source of reactive oxygen
      species, considered as the pathogenic agent of many diseases and of aging. We
      have investigated the role of Complex I in superoxide radical production in
      bovine heart submitochondrial particles and found, by combined use of specific
      inhibitors of Complex I and by Coenzyme Q (CoQ) extraction from the particles,
      that the one-electron donor in the Complex to oxygen is a redox center located
      prior to the binding sites of three different types of CoQ antagonists, to be
      identified with a Fe-S cluster, most probably N2 on the basis of several known
      properties of this cluster. Short chain CoQ analogs enhance superoxide formation,
      presumably by mediating electron transfer from N2 to oxygen. The clinically used
      CoQ analog, idebenone, is particularly effective in promoting superoxide
      formation.

PMID- 11576530
TI  - Slotoxin, alphaKTx1.11, a new scorpion peptide blocker of MaxiK channels that
      differentiates between alpha and alpha+beta (beta1 or beta4) complexes.
AB  - A novel peptide from Centruroides noxius Hoffmann scorpion venom was isolated and
      sequenced. The 37 amino acid peptide belongs to the charybdotoxin sub-family
      (alphaKTx1) and was numbered member 11. alphaKTx1.11 has 75% sequence identity
      with iberiotoxin and 54% with charybdotoxin. alphaKTx1.11 revealed specificity
      for mammalian MaxiK channels (hSlo), thus, was named slotoxin. Slotoxin blocks
      the MaxiK pore-forming alpha subunit reversibly (K(d)=1.5 nM). Slotoxin
      association with alpha+beta (beta1 or beta4) channels was approximately 10 times
      slower than iberiotoxin and charybdotoxin, leading to a lack of effect on
      alpha+beta4 when tested at 100 nM for 5 min. Thus, slotoxin is a better tool to
      distinguish MaxiK alpha+beta complexes.

PMID- 11576531
TI  - AFM force measurements on microtubule-associated proteins: the projection domain
      exerts a long-range repulsive force.
AB  - Microtubule-associated proteins (MAPs) are thought to control spacing between
      microtubules. We propose that the projection domain is largely unstructured and
      exerts a long-range repulsive force that is predominantly entropic in origin,
      providing a physical mechanism for maintaining spacing. To test this hypothesis,
      we developed an experimental system where MAPs are electrostatically end-attached
      to a flat surface, such that the projection domains extend away from the surface.
      Atomic force microscopy force measurements on this system show that projection
      domains exert a long-range (>100 nm) repulsive force. This force depends on the
      ionic strength of the solution in a way that is consistent with a polyelectrolyte
      polymer brush.

PMID- 11576532
TI  - AS-48: a circular protein with an extremely stable globular structure.
AB  - The unfolding thermodynamics of the circular enterocin protein AS-48, produced by
      Enterococcus faecalis, has been characterized by differential scanning
      calorimetry. The native structure of the 70-residue protein is extremely
      thermally stable. Thus, at pH 2.5 and low ionic strength thermal denaturation
      occurs under equilibrium at 102 degrees C, while the unfolded state irreversibly
      aggregates at neutral and alkaline pH. Calorimetric data analysis shows that the
      specific enthalpy change upon unfolding is unusually small and the heat capacity
      change is quite normal for a protein of this size, whereas the Gibbs energy
      change at 25 degrees C is relatively high. At least part of this high stability
      might be put down to entropic constraints induced by the circular organization of
      the polypeptide chain.

PMID- 11576533
TI  - A ligand that Trypanosoma cruzi uses to bind to mammalian cells to initiate
      infection.
AB  - We purified a soluble gp83 trans-sialidase (gp83-TSA), from phospholipase C
      treated Trypanosoma cruzi trypomastigote membranes, which binds to myoblasts,
      fibroblasts and macrophages to mediate trypanosome entry. Myoblasts display a
      single class of receptors for the gp83-TSA present at 4x10(4) per myoblast with a
      K(d) of 8 nM. Monovalent Fab fragments of the monoclonal antibody 4A4 specific
      for gp83-TSA inhibit gp83-TSA binding to myoblasts, fibroblasts and macrophages,
      block the trypanosomes from attaching to and entering these cells and neutralize
      T. cruzi infection in BALB/c mice. This is the first demonstration that gp83-TSA
      is a ligand that T. cruzi uses to attach to cells.

PMID- 11576534
TI  - Glucose-dependent and -independent signalling functions of the yeast glucose
      sensor Snf3.
AB  - The yeast Snf3 protein has been described to function as a sensor for low
      concentrations of extracellular glucose. We have found that Snf3 is able to
      transduce a signal in the complete absence of extracellular glucose. High basal
      activity of the HXT7 promoter during growth on ethanol required Snf3 as well as
      other components of the signalling pathway activated by Snf3. Moreover, the C
      terminal domain of Snf3 was sufficient to complement the role of Snf3 in this
      regulation. As the C-terminal tail of Snf3 interacted with other components at
      the plasma membrane independent of the carbon source, our data suggest that Snf3
      is involved in signalling complexes which can be activated by other signals than
      extracellular glucose.

PMID- 11576535
TI  - Molecular characterization of two ammonium transporters from the ectomycorrhizal
      fungus Hebeloma cylindrosporum.
AB  - Heterologous expression of the yeast triple Mep mutant has enabled the first
      molecular characterization of AMT/MEP family members in an ectomycorrhizal
      fungus. External hyphae, which play a key role in nitrogen nutrition of trees,
      are considered as the absorbing structure of the ectomycorrhizal symbiosis and
      therefore molecular studies on ammonium transport in hyphae are urgently needed.
      The kinetic properties of AMT2 and AMT3 from Hebeloma cylindrosporum were studied
      in Saccharomyces cerevisiae. Expression of HcAmts in the yeast triple Mep mutant
      restored ammonium retention within cells. The HcAmts did not complement the
      ammonium sensing defect phenotype of Mep2Delta cells during pseudohyphal
      differentiation. Northern blot analysis in H. cylindrosporum showed that the
      HcAMTs were up-regulated upon nitrogen deprivation and down-regulated by
      ammonium.

PMID- 11576536
TI  - Regulation of apoptosis by respiration: cytochrome c release by respiratory
      substrates.
AB  - Cytochrome c release from mitochondria is essential for apoptosis. Using human
      myelogenous leukemia ML-1a, its respiration-deficient and reconstituted cells, we
      demonstrated that respiratory function is essential for tumor necrosis factor
      induced cytochrome c release. In a cell free system using mitochondrial fraction
      from ML-1a, initiation of respiration by substrates for complexes I, II, and III
      but not IV released cytochrome c, suggesting that reduction of coenzyme Q or
      complex III is essential for cytochrome c release. In the same system, disruption
      of mitochondrial outer membrane was neither enough nor the cause for cytochrome c
      release by succinate. These observations define an early pathway in which a
      change in respiration releases cytochrome c.

PMID- 11576537
TI  - Sites of interaction of thioredoxin with sorghum NADP-malate dehydrogenase.
AB  - The activation pathway of the chloroplastic NADP-dependent malate dehydrogenase
      (MDH) by reduced thioredoxin has been examined using a method based on the
      mechanism of thiol/disulfide interchanges, i.e. the transient formation of a
      mixed disulfide between the target and the reductant. This disulfide can be
      stabilized when each of the partners is mutated in the less reactive cysteine of
      the disulfide/dithiol pair. As NADP-MDH has two regulatory disulfides per
      monomer, four different single cysteine mutants were examined, two for the C
      terminal bridge and two for the N-terminal bridge. The results clearly show that
      the nucleophilic attack of thioredoxin on the C-terminal bridge proceeds through
      the formation of a disulfide with the most external Cys377. The results are less
      clear-cut for the N-terminal cysteines and suggest that the Cys24-Cys207
      disulfide bridge previously proposed to be an intermediary step in MDH activation
      can form only when the C-terminal disulfide is reduced.

PMID- 11576538
TI  - Structure requirement and identification of a cryptic cleavage site in the
      mitochondrial processing of a plant F1-ATPase beta-subunit presequence.
AB  - We sought to determine the structural features involved in the processing of the
      mitochondrial F1-ATPase beta-subunit (F1beta) presequence (54 residues) from
      Nicotiana plumbaginifolia. The cleavage efficiency of F1beta presequence mutants
      linked to the green fluorescent protein (GFP) was evaluated in vivo in tobacco by
      in situ microscopy and Western blotting. The residue at position -1 (Tyr) was
      required to be an aromatic residue and the residue at position +2 (Thr) was found
      to be important for F1beta processing, while, unexpectedly, changing the distal
      (Arg-15) and proximal (Arg-5) arginine residues did not strongly reduce
      processing. In addition, results also supported the requirement of a helical
      structure around the cleavage position. Sequencing of the mature form of a
      precursor containing the first 30 residues of the F1beta presequence linked to
      GFP revealed the presence of a cryptic cleavage site between residues 26 and 27,
      which showed the features of a classical mitochondrial processing site,
      suggesting dual processing of the F1beta presequence. In vitro processing
      confirmed these data and showed that processing was sensitive to o
      phenanthroline, thus catalyzed by mitochondrial processing peptidase.

PMID- 11576539
TI  - Direct observation of membrane retrieval in chromaffin cells by capacitance
      measurements.
AB  - This study was focussed on the identification of the endocytic organelles in
      chromaffin cells which retrieve large, dense core vesicle (LDCV)-membrane
      components from the plasma membrane. For this purpose, 'on-cell' capacitance
      measurements and electron microscopy were employed. We found capacitance steps
      and capacitance flickers, corresponding to single exo- and endocytic events. The
      analysis revealed that the total membrane surface of completely fused LDCVs is
      recycled by large endocytic vesicles and smaller, most likely clathrin-coated
      vesicles, at approximately the same ratio. These results were confirmed by rapid
      freeze immuno-electron microscopy, where an extracellular marker was rapidly
      internalized into endocytic vesicles that morphologically resembled LDCVs.

PMID- 11576540
TI  - Identification of the cardiac ryanodine receptor channel in membrane blebs of
      sarcoplasmic reticulum.
AB  - Blebs of the sarcoplasmic reticulum (SR) membrane of heart muscle cells were
      generated after saponin perforation of the plasma membrane followed by complete
      hypercontraction of the cell. Although characteristic proteins of the plasma
      membrane, namely the beta1-adrenoreceptor and Galphai, were stained by monoclonal
      antibodies in the hypercontracted cells, these proteins could not be detected in
      the adjacent blebs. Monoclonal antibodies to the cardiac ryanodine receptor
      (RyR2), calsequestrin and SERCA2 bound at different amounts to surface components
      of the blebs and to components of the hypercontracted cells. From the
      immunofluorescence signals we conclude that the blebs are mainly constituted of
      corbular and junctional SR membrane, and only to a lesser extent of network SR
      membrane. Deconvolution microscopy revealed that the membrane location of RyR2,
      calsequestrin and SERCA2 in the bleb is comparable to native SR membrane. At the
      bleb membrane giga-ohm seals could be obtained and patches could be excised in a
      way that single-channel currents could be measured, although these are not
      completely identified.

PMID- 11576541
TI  - Identification of essential acidic residues of outer membrane protease OmpT
      supports a novel active site.
AB  - Escherichia coli outer membrane protease OmpT has previously been classified as a
      serine protease with Ser(99) and His(212) as active site residues. The recently
      solved X-ray structure of the enzyme was inconsistent with this classification,
      and the involvement of a nucleophilic water molecule was proposed. Here, we
      substituted all conserved aspartate and glutamate residues by alanines and
      measured the residual enzymatic activities of the variants. Our results support
      the involvement of a nucleophilic water molecule that is activated by the
      Asp(210)/His(212) catalytic dyad. Activity is also strongly dependent on Asp(83)
      and Asp(85). Both may function in binding of the water molecule and/or oxyanion
      stabilization. The proposed mechanism implies a novel proteolytic catalytic site.

PMID- 11576542
TI  - Investigating the conformational coupling between the transmembrane and
      cytoplasmic domains of a single-spanning membrane protein. A 1H-NMR study.
AB  - PMP1 is a 38-residue single-spanning membrane protein whose C-terminal
      cytoplasmic domain, Y25-F38, is highly positively charged. The conformational
      coupling between the transmembrane span and the cytoplasmic domain of PMP1 was
      investigated from 1H-nuclear magnetic resonance data of two synthetic fragments:
      F9-F38, i.e. 80% of the whole sequence, and Y25-F38, the isolated cytoplasmic
      domain. Highly disordered in aqueous solution, the Y25-F38 peptide adopts a well
      defined conformation in the presence of dodecylphosphocholine micelles. Compared
      with the long PMP1 fragment, this structure exhibits both native and non-native
      elements. Our results make it possible to assess the influence of a hydrophobic
      anchor on the intrinsic conformational propensity of a cytoplasmic domain.

PMID- 11576543
TI  - Stability and DNA-binding properties of the omega regulator protein from the
      broad-host range Streptococcus pyogenes plasmid pSM19035.
AB  - At the transcriptional level, the pSM19035-encoded omega protein coordinates the
      expression of proteins required for control of copy number and maintenance of
      plasmids. Using circular dichroism, fluorescence spectroscopy,
      ultracentrifugation and an electrophoretic mobility shift assay, the wild-type
      omega protein and a variant with a C-terminal hexa-histidine tag (omega-H(6))
      were characterized. The omega protein is mainly alpha-helical (42%), occurs as
      homodimer in solution, unfolds thermally with half transition temperatures, T(m),
      between approximately 43 and approximately 78 degrees C depending on the ionic
      strength of the buffer, and binds PcopS-DNA with high affinity. The omega-H(6)
      protein has a modified conformation with lower alpha-helix content (29%), lower
      thermal stability, and strongly reduced affinity to PcopS-DNA.

PMID- 11576544
TI  - Skeletal and cardiac ryanodine receptors bind to the Ca(2+)-sensor region of
      dihydropyridine receptor alpha(1C) subunit.
AB  - In striated muscles, excitation-contraction coupling is mediated by the
      functional interplay between dihydropyridine receptor L-type calcium channels
      (DHPR) and ryanodine receptor calcium-release channel (RyR). Although
      significantly different molecular mechanisms are involved in skeletal and cardiac
      muscles, bidirectional cross-talk between the two channels has been described in
      both tissues. In the present study using surface plasmon resonance spectroscopy,
      we demonstrate that both RyR1 and RyR2 can bind to structural elements of the C
      terminal cytoplasmic domain of alpha(1C). The interaction is restricted to the CB
      and IQ motifs involved in the calmodulin-mediated Ca(2+)-dependent inactivation
      of the DHPR, suggesting functional interactions between the two channels.

PMID- 11576545
TI  - Heparan N-sulfatase: cysteine 70 plays a role in the enzyme catalysis and
      processing.
AB  - Sulfatases are members of a highly conserved family of enzymes that catalyze the
      hydrolysis of sulfate ester bonds from a variety of substrates. The functional
      correlation reflects a high degree of amino acid sequence similarity along the
      entire length, in particular in the active site where the C(X)PSR consensus
      sequence is present. Cysteine undergoes an important co- or post-translation
      modification essential for the accomplishment of catalytic activity: conversion
      in formylglycine. In this work, the cysteine of heparan N-sulfatase (NS) was
      replaced either by a serine (C70S) or by a methionine (C70M) using site-directed
      mutagenesis. C70S and C70M mutant cDNAs were expressed and analyzed in COS cells;
      both mutations caused a loss of NS activity; however, while C70S showed a normal
      precursor form undergoing processing to a reduced mature form within the
      lysosomes, C70M was poorly synthesized and formed a complex with the molecular
      chaperone immunoglobulin binding protein.

PMID- 11576546
TI  - 'Empty' minicircles and petB/atpA and psbD/psbE (cytb559 alpha) genes in tandem
      in Amphidinium carterae plastid DNA.
AB  - Amphidinium carterae minicircle chloroplast DNA was separated from total DNA by
      centrifugation through a sucrose/NaCl gradient. Sequences of minicircles with
      psbA and 23S rRNA contained a common region of 67 bp. Primers designed from this
      generated numerous polymerase chain reaction products of 1.5-2.6 kb. These
      contained psaA and psaB as one gene/circle, and petB/atpA and psbD/psbE as two
      genes/circle. 'Empty' minicircles of 1.7-2.5 kb containing no identifiable genes
      or parts of genes were more abundant than gene-containing circles. From 15
      minicircles a minimum common region of 48 bp was identified, with little identity
      to that from other dinoflagellate minicircles.

PMID- 11576547
TI  - Oligomeric C-terminal truncated Bax preferentially releases cytochrome c but not
      adenylate kinase from mitochondria, outer membrane vesicles and proteoliposomes.
AB  - The mechanism by which the proapoptotic protein Bax releases cytochrome c from
      mitochondria is not fully understood. The present work approaches this problem
      using C-terminal truncated oligomeric Bax (BaxDeltaC). Micromolar concentrations
      of BaxDeltaC released cytochrome c from isolated rat heart and liver
      mitochondria, while the release of adenylate kinase was not significantly
      affected. BaxDeltaC also released cytochrome c but not adenylate kinase from
      outer membrane vesicles filled with these proteins. However, BaxDeltaC was
      ineffective in releasing cytochrome c when outer membrane vesicles were obtained
      in the presence of glycerol, conditions under which the number of contact sites
      was drastically reduced. BaxDeltaC did not liberate encapsulated cytochrome c and
      adenylate kinase from pure phospholipid vesicles or vesicles reconstituted with
      porin. However, when the hexokinase-porin-adenine nucleotide translocase complex
      from brain mitochondria was reconstituted in vesicles, BaxDeltaC released
      internal cytochrome c but not adenylate kinase. In all these systems, only a
      small portion of total cytochrome c present in either mitochondria or vesicles
      could be liberated by BaxDeltaC. BaxDeltaC also increased the accessibility of
      external cytochrome c to either oxidation by complex IV or reduction by complex
      III in intact liver and heart mitochondria. CONCLUSIONS: (1) BaxDeltaC
      selectively releases cytochrome c and enables a bidirectional movement of
      cytochrome c across the outer mitochondrial membrane. (2) A multiprotein complex
      that resembles the mitochondrial contact sites is a prerequisite for BaxDeltaC
      action. (3) A limited pool of cytochrome c becomes the first target for
      BaxDeltaC.

PMID- 11576548
TI  - Inhibition of Src by direct interaction with protein phosphatase 2A.
AB  - In this study, we report that Src kinase is inhibited by protein phosphatase 2A
      (PP2A), a serine/threonine phosphatase. We carried out experiments in vitro using
      purified PP2A (AC dimer) and full-length v-Src or truncated forms of v-Src. The
      inhibition of v-Src by PP2A is concentration- and time-dependent. Addition of
      okadaic acid, a PP2A phosphatase inhibitor, abolished the PP2A-dependent
      inhibition of v-Src. When experiments were carried out at 4 degrees C under
      conditions where PP2A activity is inhibited, Src activity was unaffected by the
      presence of PP2A, suggesting that PP2A binding alone is insufficient to block Src
      activity. These results imply that PP2A activity is essential for inhibition of v
      Src. We also demonstrate that PP2A binds to the catalytic and the regulatory
      domains of v-Src.

PMID- 11576551
TI  - Using an in vivo phagemid system to identify non-compatible loxP sequences.
AB  - The site-specific recombination system of bacteriophage P1 is composed of the Cre
      recombinase that recognizes a 34-bp loxP site. The Cre/loxP system has been
      extensively used to manipulate eukaryotic genomes for functional genomic
      investigations. The creation of additional heterologous loxP sequences
      potentially expands the utility of this system, but only if these loxP sequences
      do not recombine with one another. We have developed a stringent in vivo assay to
      examine the degree of recombination between all combinations of each previously
      published heterologous loxP sequence. As expected, homologous loxP sequences
      efficiently underwent Cre-mediated recombination. However, many of the
      heterologous loxP pairs were able to support recombination with rates varying
      from 5 to 100%. Some of these loxP sequences have previously been reported to be
      non-compatible with one another. Our study also confirmed other heterologous loxP
      pairs that had previously been shown to be non-compatible, as well as defined
      additional combinations that could be used in designing new recombination
      vectors.

PMID- 11576559
TI  - Low level viral persistence after infection with LCMV: a quantitative insight
      through numerical bifurcation analysis.
AB  - Many important viruses persist at very low levels in the body in the face of host
      immunity, and may influence the maintenance of this state of 'infection
      immunity'. To analyse low level viral persistence in quantitative terms, we use a
      mathematical model of antiviral cytotoxic T lymphocyte (CTL) response to
      lymphocytic choriomeningitis virus (LCMV). This model, described by a non-linear
      system of delay differential equations (DDEs), is studied using numerical
      bifurcation analysis techniques for DDEs. Domains where low level LCMV
      coexistence with CTL memory is possible, either as an equilibrium state or an
      oscillatory pattern, are identified in spaces of the model parameters
      characterising the interaction between virus and CTL populations. Our analysis
      suggests that the coexistence of replication competent virus below the
      conventional detection limit (of about 100 pfu per spleen) in the immune host as
      an equilibrium state requires the per day relative growth rate of the virus
      population to decrease at least 5-fold compared to the acute phase of infection.
      Oscillatory patterns in the dynamics of persisting LCMV and CTL memory, with
      virus population varying between 1 and 100 pfu per spleen, are possible within
      quite narrow intervals of the rates of virus growth and precursor CTL population
      death. Whereas the virus replication rate appears to determine the stability of
      the low level virus persistence, it does not affect the steady-state level of the
      viral population, except for very low values.

PMID- 11576560
TI  - On the importance of risky behavior in the transmission of sexually transmitted
      diseases.
AB  - We consider a population with two types of individuals: those who engage in risky
      sexual behavior (the core) and those who do not (the majority). We are interested
      in the situation where the majority would not be able to sustain an epidemic
      without the presence of a core. We show that even if the core is randomly spread
      out in the general population and is very infectious there will be no epidemic if
      the proportion of individuals in the core is below a certain threshold (that
      depends on the infection rates). Risky behavior does put the whole population at
      risk but only if the behavior is widespread enough. This gives support to the
      idea of concentrating resources to fight sexually transmitted diseases on the
      core group in order to lower the proportion of individuals in the core. We show
      our results for two models: one with total mixing and the other with limited
      mixing.

PMID- 11576561
TI  - Dispersal, disease and life-history evolution.
AB  - Discrete-time susceptible-infective-susceptible (S-I-S) disease transmission
      models can exhibit bistability (alternative stable equilibria) over a wide range
      of parameter values. We illustrate the richness generated by such 'simple' non
      linear systems in the study of two patch epidemic models with disease-enhanced or
      disease-suppressed dispersal. Dispersal between patches can have a profound
      impact on local patch disease dynamics. In fact, dispersal between patches may
      give rise to bistability in parameter regimes without bistability in single patch
      models.

PMID- 11576562
TI  - Lights! Camera! Action!

PMID- 11576563
TI  - Privacy lost.

PMID- 11576564
TI  - Let's take the high road.

PMID- 11576565
TI  - Caring.

PMID- 11576566
TI  - Active phase labor arrest: revisiting the 2-hour minimum.
AB  - OBJECTIVE: To generate contemporary uterine activity and labor progress data for
      oxytocin-augmented labor, and assess whether 2 hours of active phase labor arrest
      with at least 200 Montevideo units justifies cesarean delivery. METHODS: Five
      hundred and one consecutive spontaneously laboring term women with abnormally
      progressive labor were managed by a standardized protocol: oxytocin and
      intrauterine pressure catheter with an intent to sustain at least 200 Montevideo
      units for 4 hours or more before cesarean for labor arrest. Uterine activity was
      measured, and maternal and neonatal outcomes were evaluated. With a sample of
      this size, the upper 95% confidence interval limit for an event with an observed
      rate of 1% is below 3%. RESULTS: During oxytocin augmentation, nulliparas who
      were delivered vaginally dilated at a median rate of 1.4 cm/hour versus 1.8
      cm/hour for parous women. In both groups, the 5th percentile of cervical dilation
      rate was 0.5 cm/hour. Thirty-eight women experienced labor arrest for over 2
      hours despite at least 200 sustained Montevideo units; 23 (61%) achieved a
      vaginal delivery. Rates of chorioamnionitis and endometritis for the 38 women
      were 26%. None of their infants sustained a serious complication, including
      brachial plexus injury, even though three of the 23 vaginal deliveries (13%) were
      complicated by shoulder dystocia. CONCLUSION: These data demonstrate that
      oxytocin-augmented labor proceeds at substantially slower rates than spontaneous
      labor, and support our previous contention that the criteria of labor arrest for
      2 hours, despite at least 200 sustained Montevideo units, are insufficiently
      rigorous for the performance of cesarean.

PMID- 11576567
TI  - Sulindac to prevent recurrent preterm labor: a randomized controlled trial.
AB  - OBJECTIVE: To assess the efficacy of oral sulindac in low doses for prolonged
      duration to decrease the risk of recurrent preterm labor and extend gestation.
      METHODS: This was a randomized, double-blind, placebo-controlled study of
      patients between 24 and 34 weeks' gestation with preterm labor treated with
      intravenous magnesium sulfate. After successful tocolysis, patients were
      randomized by the pharmacy to receive either oral sulindac (100 mg) or placebo
      orally every 12 hours until 34 weeks' gestation. A power analysis required 43
      patients in each group. RESULTS: Ninety-five patients were enrolled (46 in the
      sulindac group, 49 controls). No significant differences were found with respect
      to time gained in utero (39 +/- 25 versus 45 +/- 26 days, P = .29), delivery at
      more than 35 weeks' gestation (61% versus 74%, P = .29), recurrent preterm labor
      (20% versus 18%, P = .86), birth weight (2562 +/- 623 versus 2624 +/- 543 g, P =
      .62), or time spent in the neonatal intensive care unit (2.8 +/- 9.2 versus 2.4
      +/- 8.6 days, P = .83) for the sulindac and control groups, respectively.
      CONCLUSION: The use of oral sulindac until 34 weeks' gestation after successful
      parenteral tocolysis failed to reduce the incidence of readmission for preterm
      labor.

PMID- 11576568
TI  - Uterine relaxant effects of cyclooxygenase-2 inhibitors in vitro.
AB  - OBJECTIVE: To compare the effects of three cyclooxygenase-2 (COX-2) inhibitors:
      nimesulide, meloxicam, and celecoxib, which exhibit varying COX-2 selectivity, on
      contractile activity in pregnant (before and after labor) and nonpregnant human
      myometrial tissue in vitro. METHODS: Isometric tension recording was performed
      under physiologic conditions in isolated myometrial strips obtained from 33 women
      undergoing hysterectomy or either elective or emergency cesarean section. The
      effects of cumulative additions of nimesulide, meloxicam, and celecoxib (between
      1 nmol/L and 100 micromol/L) on myometrial contractility were measured, and
      values for -log(10) EC(50) and mean maximal inhibition were compared. RESULTS:
      Nimesulide, meloxicam, and celecoxib exerted significant relaxant effects on
      contractility in nonpregnant, pregnant nonlabor, and pregnant labor myometrial
      strips. Values for -log(10) EC(50) values (+/- standard error of the mean) were
      as follows: nimesulide (nonpregnant) 5.14 +/- 0.93 (n = 6), (pregnant nonlabor)
      4.91 +/- 0.75 (n = 6), and (pregnant labor) 5.84 +/- 0.35 (n = 6); meloxicam
      (nonpregnant) 6.53 +/- 0.57 (n = 6), (pregnant nonlabor) 4.80 +/- 0.71 (n = 6),
      and (pregnant labor) 5.62 +/- 0.21 (n = 6); celecoxib (nonpregnant) 6.15 +/- 0.99
      (n = 6), (pregnant nonlabor) 7.08 +/- 0.98 (n = 6), and (pregnant labor) 7.25 +/-
      0.99 (n = 3). Celecoxib exhibited greater potency than nimesulide or meloxicam (P
      < .01). The range of maximal relaxation values achieved in the three tissue types
      were as follows: nimesulide 68-70% (n = 18; P < .01), meloxicam 69-84% (n = 18; P
      < .01), and celecoxib 69-77% (n = 15; P < .01). CONCLUSION: COX-2 inhibitors
      exert significant relaxation in human myometrium with a similar potency in
      nonpregnant and pregnant (before and after labor onset) tissues. Celecoxib, a COX
      2 specific inhibitor, was more potent than nimesulide or meloxicam, COX-2
      preferential inhibitors.

PMID- 11576569
TI  - Emergency contraception: randomized comparison of advance provision and
      information only.
AB  - OBJECTIVE: To determine whether multiple courses of emergency contraceptive
      therapy supplied in advance of need would tempt women using barrier methods to
      take risks with their more effective ongoing contraceptive methods. METHODS: We
      randomly assigned 411 condom users attending an urban family planning clinic in
      Pune, India, to receive either information about emergency contraception along
      with three courses of therapy to keep in case of need, or to receive only
      information, including that about the locations where they could obtain emergency
      contraception if needed. For up to 1 year, women returned quarterly for follow
      up, answering questions about unprotected intercourse, emergency contraceptive
      use, pregnancies, sexually transmitted infections, and acceptability. RESULTS:
      Women given advance supplies reported unprotected intercourse at rates nearly
      identical to those among women given only information (0.012 versus 0.016 acts
      per month). Among those who did have unprotected intercourse, however, supply
      recipients were nearly twice as likely (79% versus 44%) to have taken emergency
      contraception, although numbers were too small to permit statistically
      significant inferences. No women used emergency contraception more than once
      during the study, even though everyone in the advance-supplies group had extra
      doses available. All women found knowing about emergency contraception useful,
      and all those receiving only information wished they had received supplies as
      well. CONCLUSION: Multiple emergency contraception doses supplied in advance did
      not tempt condom users to risk unprotected intercourse. After unprotected
      intercourse, however, those with pills on hand used them more often. Women found
      advance provision useful.

PMID- 11576571
TI  - Outcome and resource use associated with myomectomy.
AB  - OBJECTIVE: To evaluate the outcomes and cost of myomectomy through retrospective
      claims data analysis. METHODS: The study was performed using a retrospective
      database of private insurance claims from 1995 to 1997. Records were selected for
      analysis based on the presence of ICD-9-CM procedure and/or CPT-4 codes
      associated with myomectomy. In addition, diagnosis of uterine leiomyoma and
      related symptoms for these patients were confirmed through ICD-9-CM diagnosis
      codes. Inpatient, outpatient, and physician costs were estimated. All cost data
      were converted into 1997 dollars. RESULTS: A total of 4394 women, between the
      ages of 14 and 70, were available for analysis. Of these, 3305 were classified by
      type of myomectomy procedure, and complete data were available on 820 at 1 year
      and 236 at 2 years. Abdominal myomectomies were the most common procedures,
      followed by hysteroscopic and laparoscopic myomectomies. Conversion to a more
      invasive procedure occurred in 5.4% of the patients. The rate of additional
      surgeries was 8.3% in 6 months, 10.6% in 1 year, and 16.5% in 2 years. Overall
      cost increased from an initial 6,737 dollars per patient to 7,575 dollars in 1
      year and to 8,001 dollars in 2 years. CONCLUSION: The repeat procedures required
      after the initial myomectomy add significantly to total cost and highlight the
      importance of assessing post-procedure health care use. This comprehensive
      analysis facilitates the systematic evaluation of myomectomy with current and
      emerging alternative treatments for uterine leiomyomas.

PMID- 11576570
TI  - A prospective, controlled study of the effects of hormonal contraception on bone
      mineral density.
AB  - OBJECTIVE: To compare the effect of depot medroxyprogesterone acetate (DMPA) and
      two types of oral contraceptives (OC) on bone mineral density (BMD) among women
      18-33 years of age with those not using hormonal contraception. METHODS: Data
      from 155 women were analyzed. Depot medroxyprogesterone acetate was administered
      to 33 women; 63 women who chose oral contraception were randomly assigned to
      receive either a norethindrone-containing pill (n = 28) or a desogestrel
      containing pill (n = 35). Fifty-nine women who did not use hormonal contraception
      served as controls. Lumbar spine BMD was determined using dual-energy x-ray
      absorptiometry at baseline and after 12 months of contraceptive use. We analyzed
      method-related percent change in BMD while controlling for body mass index,
      calcium intake, exercise, and smoking. We had approximately 90% power to detect a
      2.5% difference between any two groups. RESULTS: Users of DMPA experienced a mean
      BMD loss of 2.74% over 12 months compared with controls who sustained a 0.37%
      loss (P = .01). Users of OCs generally demonstrated a gain (2.33% for
      norethindrone-containing pills, 0.33% for desogestrel-containing pills), which
      was different from controls among users of norethindrone-containing pills (P =
      .01), but not among users of desogestrel-containing pills (P = .99). Observed
      changes in BMD among DMPA users differed from women who used either type of pill
      (P < .002). CONCLUSION: Depot medroxyprogesterone acetate has an adverse effect
      on BMD, in comparison with OCs or nonhormonal methods, when used for 12 months.
      Results must be interpreted cautiously until it is determined whether these
      effects endure or are reversible.

PMID- 11576572
TI  - Clobetasol propionate in the treatment of premenarchal vulvar lichen sclerosus.
AB  - OBJECTIVE: To assess the effectiveness of treating premenarchal vulvar lichen
      sclerosus with clobetasol propionate. METHODS: A retrospective chart review was
      performed of girls presenting to the University of Michigan Pediatric and
      Adolescent Gynecology Clinic from January, 1995, to July, 2000, with premenarchal
      lichen sclerosus. Subjects in the study were treated with topical clobetasol
      propionate ointment 0.05% for 2-4 weeks, and then tapered to a less potent
      steroid. Information was extracted concerning age at onset, symptoms, vulvar
      examination, previous treatments, effectiveness of clobetasol, follow-up, and
      complications. The parents were contacted for a follow-up telephone survey.
      RESULTS: Fifteen girls averaging 5.7 years at the start of symptoms met criteria.
      The diagnosis of lichen sclerosus was made visually in 11 and by biopsy in four.
      Follow-up ranged from 2 months to 6 years. Fourteen girls had good improvement
      within 4-7 weeks. One girl developed a yeast superinfection and one developed
      transient erythema. At least 1 year of follow-up by clinic visit or telephone
      interview was available in 11 girls. Of these 11, two girls had no further vulvar
      symptoms after the initial treatment, five had one or two total flares, three
      reported three to eight flares per year, and one girl continues to be
      unresponsive to therapy. CONCLUSION: Clobetasol propionate was an effective
      treatment of premenarchal vulvar lichen sclerosus in this small group; however,
      recurrences were common and required additional steroid treatment. Furthermore,
      complications of treatment were infrequent, minor, and easily treatable.

PMID- 11576573
TI  - Lidocaine versus plain saline for pain relief in fractional curettage: a
      randomized controlled trial.
AB  - OBJECTIVE: To compare the efficiency of lidocaine with that of plain saline for
      paracervical pain relief during fractional curettage. METHODS: This double-blind,
      randomized, controlled trial included 140 women who underwent fractional
      curettage. Seventy women were allocated to the lidocaine group and 70 to the
      plain saline group. The main outcome measure was the intensity of pain measured
      by visual analog scale during and after the procedure. RESULTS: The intensity of
      pain was significantly lower in the lidocaine group than in the plain saline
      group over the course of the procedure (P = .02), especially during fractional
      curettage. There were no serious adverse effects in this study. CONCLUSION:
      Lidocaine is more effective than plain saline for paracervical pain relief during
      fractional curettage. The anesthetic mechanisms of lidocaine are mechanical
      distention of tissue and peripheral nerve block.

PMID- 11576574
TI  - Preeclampsia: is there value in assessing before clinically evident disease?

PMID- 11576575
TI  - Plasma placenta growth factor levels in midtrimester pregnancies.
AB  - OBJECTIVE: Previous studies have shown decreased levels of placenta growth factor
      in serum of pregnant women with preeclampsia. The aim of this study was to
      investigate whether levels of placenta growth factor are decreased before the
      clinical onset of preeclampsia, and whether placenta growth factor levels are
      decreased in pregnancies complicated by intrauterine growth restriction. METHODS:
      From an ongoing longitudinal study, 101 plasma samples were collected from 72
      pregnant women at weeks 11-21 of gestation. Placenta growth factor levels were
      determined retrospectively in plasma using an enzyme-linked immunosorbent assay.
      Correlations between plasma concentrations of placenta growth factor and
      pregnancy outcome were evaluated. RESULTS: Plasma samples of 72 patients were
      analyzed. Forty-four patients had no pregnancy complications, 18 developed
      preeclampsia, and 10 women had pregnancies complicated by intrauterine growth
      restriction. Between week 17 and week 21 of pregnancy, a significantly lower
      level of placenta growth factor was found in plasma of patients who later
      developed preeclampsia (n = 10), compared with control pregnancies (n = 25, P =
      .004). In women with a growth-restricted baby at birth (n = 5), levels of
      placenta growth factor were also low. CONCLUSIONS: Our results show that plasma
      placenta growth factor levels are decreased before preeclampsia is clinically
      evident. The data suggest that placenta growth factor may be useful to determine
      the relative risk of developing preeclampsia and intrauterine growth restriction.

PMID- 11576576
TI  - First-trimester maternal serum levels of placenta growth factor as predictor of
      preeclampsia and fetal growth restriction.
AB  - OBJECTIVE: To determine whether the reported decrease in maternal serum placenta
      growth factor concentration in preeclampsia is evident from the first trimester
      and before clinical onset of the disease. We also examined levels in pregnancies
      that subsequently resulted in fetal growth restriction (FGR). METHODS: Placenta
      growth factor concentration was measured in stored maternal serum samples
      obtained at 11-14 weeks of gestation from 131 women who subsequently developed
      preeclampsia, 137 women who subsequently developed FGR, and 400 randomly selected
      controls who did not develop preeclampsia or FGR. Preeclampsia was defined as
      diastolic blood pressure of 90 mmHg or more on two occasions 4 hours apart,
      accompanied by proteinuria (more than 300 mg of total protein in a 24-hour urine
      collection or a positive test for albumin on reagent strip) in women with no pre
      existing hypertensive or renal disease. Fetal growth restriction was considered
      present if a woman subsequently delivered a live infant with a birth weight below
      the fifth centile for gestation. RESULTS: In the control group, maternal serum
      placenta growth factor concentration increased with gestation. Compared with the
      controls (median multiple of the median 0.98, standard deviation [SD] 0.51),
      levels in the preeclampsia group (median multiple of the median 1.09, SD 0.52)
      were not significantly different (t = 1.83, P = .07), but in the FGR group
      (median multiple of the median 1.57, SD 0.74), levels were significantly
      increased (t = 10.85, P < .001). CONCLUSION: The previously reported decrease in
      serum placenta growth factor levels in women with preeclampsia might not precede
      clinical onset of the disease and is not apparent in the first trimester of
      pregnancy. Levels are significantly increased in pregnancies resulting in FGR.

PMID- 11576577
TI  - Polymorphisms in the tumor necrosis factor and lymphotoxin-alpha gene region and
      preeclampsia.
AB  - OBJECTIVE: To investigate potential association or linkage among nine
      polymorphisms in the genes encoding tumor necrosis factor (TNF) alpha or
      lymphotoxin (LT) alpha and preeclampsia. METHODS: Four di-allelic polymorphisms
      and five microsatellite markers in the genes encoding TNF-alpha (TNF) and LTalpha
      (LTA) and their haplotypes were studied in 150 Dutch families. These families
      contained sib-pairs of women affected with preeclampsia; eclampsia; the
      hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (strict
      criteria); or pregnancy-induced hypertension (mild criteria). Frequencies were
      compared with 98 healthy controls. Nonparametric affected sib-pair analyses for
      allele sharing among siblings were carried out for all nine markers. Each sibship
      was composed of an affected index woman and one or more affected sisters.
      RESULTS: Although we found a striking association with the TNF-I haplotype in 30
      index women with (pre-)eclampsia or HELLP syndrome compared with controls (odds
      ratio [OR] 3.8; 95% confidence interval [CI] 1.6, 8.9), this association was not
      found in their 30 sisters meeting similar disease criteria. Analyses in all 150
      families showed a similar TNF-I association in 122 index women meeting the strict
      criteria compared with controls (OR 1.9; 95% CI 1.1, 3.3), but, again, not in
      their 91 sisters meeting similar disease criteria. This association was stronger
      in a subgroup of 75 index women with preeclampsia only (OR 2.3; 95% CI 1.2, 4.2).
      No excess allele sharing for any marker was seen between the siblings.
      CONCLUSION: The nine polymorphisms studied in the TNF-LTA region did not show
      evidence for association or linkage with familial preeclampsia.

PMID- 11576578
TI  - Infant mortality from congenital malformations in the United States, 1970-1997.
AB  - OBJECTIVE: We examined a trend in infant mortality caused by congenital
      malformations in the United States, particularly for the racial disparity between
      whites and nonwhites. METHODS: We used US annual summary data on cause-specific
      infant mortality for 1970-97 and detailed birth and infant death linked data for
      1985-87, 1989-91, and 1995-97. RESULTS: Congenital malformations became a more
      prominent cause of infant mortality in 1997 and accounted for 22.1% of all infant
      deaths compared with 15.1% in 1970. Congenital malformations of nervous,
      cardiovascular, and respiratory systems accounted for more than 60% of all
      malformation deaths. Malformations incompatible with life (anencephaly,
      encephalocele, hypoplastic lungs, renal agenesis, and trisomies 13 and 18) were
      the cause of one-third of all malformation deaths. In 1970-71, infant mortality
      caused by congenital malformations in nonwhites was lower, 2.6 (confidence
      interval [CI] 2.5, 2.7) per 1000, compared with whites, 3.1 (CI 3.0, 3.1) per
      1000. However, in 1996-97, the rate of congenital malformation-specific infant
      mortality was higher in nonwhites, 1.7 (CI 1.7, 1.8) per 1000, compared with
      whites, 1.6 (CI 1.5, 1.6) per 1000. This trend was most pronounced with central
      nervous system malformations. Although whites had an almost two-fold higher
      infant mortality rate from central nervous system malformations compared with
      nonwhites in 1970-71, this disparity was no longer present by 1996-97.
      CONCLUSION: Congenital malformations have become a leading cause of infant
      mortality in the 1990s. Over the last several decades, this mortality declined
      more slowly in nonwhites than in whites.

PMID- 11576579
TI  - Is incontinence associated with menopause?
AB  - OBJECTIVES: To estimate (1) the prevalence of urinary incontinence in a
      population-based sample of Australian women aged 45-55 and to identify the
      factors associated with urinary incontinence; (2) the incidence of urinary
      incontinence over a 7-year follow-up period and to identify whether the
      transition from pre- to postmenopause is associated with the development of
      urinary incontinence. METHODS: This was a cross-sectional study of 1897 women and
      a 7-year longitudinal follow-up of 373 of these women who were premenopausal at
      baseline. Annual interviews and physical measurements were taken in their homes.
      RESULTS: Cross-sectional: the prevalence of urinary incontinence was 15%;
      multivariate analysis found that urinary incontinence patients were significantly
      more likely than those without incontinence to have higher body mass index (odds
      ratio [OR] 1.50, 95% confidence interval [CI] 1.15, 1.95), have had gynecologic
      surgery (OR 2.17, 95% CI 1.42, 3.32), report urinary tract infections (OR 4.75,
      95% CI 2.28, 9.90), diarrhea or constipation (OR 1.95, 95% CI 1.27, 3.00), and
      have had three or more children (OR 1.47, 95% CI 1.06, 2.05). Longitudinal:
      during the 7-year follow-up, the average prevalence of urinary incontinence was
      18% and the overall incidence 35%. Women who experienced a hysterectomy during
      the follow-up period had a higher incidence. CONCLUSION: Urinary incontinence in
      middle-aged women is more closely associated with mechanical factors than with
      menopausal transition.

PMID- 11576580
TI  - Enterocele: is there a histologic defect?
AB  - OBJECTIVE: To examine the histology of the vaginal wall in women with an
      enterocele confirmed by physical examination, cystoproctography, and
      intraoperative exploration. METHODS: Thirteen women with posthysterectomy apical
      and posterior wall prolapse were evaluated with a detailed physical examination,
      cystoproctography, and intraoperative exploration. All women had enterocele
      repair. A specimen of full thickness vaginal wall from the leading edge of the
      enterocele was excised and examined histologically. The histology of these
      patients was compared with the histology of two comparison groups, five women
      undergoing hysterectomy without prolapse and 13 women undergoing radical
      hysterectomy. RESULTS: One woman with an enterocele repaired intraoperatively did
      not have an enterocele by cystoproctography. One woman with an enterocele
      repaired intraoperatively did not have an enterocele detected by physical
      examination. All women with an enterocele repaired had an intact vaginal wall
      muscularis. No woman had vaginal wall epithelium in direct contact with the
      peritoneum. The average vaginal wall muscularis thickness in women with
      enteroceles was 3.5 +/- 1.4 mm, in women with no prolapse 3.2 +/- 0.8 mm, and in
      women undergoing radical hysterectomy 2.8 +/- 0.9 mm. CONCLUSION: Women with
      enteroceles have a well-defined vaginal muscularis between the peritoneum and
      vaginal epithelium.

PMID- 11576581
TI  - Effect of tension-free vaginal tape procedure on urodynamic continence indices.
AB  - OBJECTIVE: To assess the difference in measured urethral function before and
      after tension-free vaginal tape procedure (TVT). METHODS: Women who underwent TVT
      for genuine stress incontinence with or without intrinsic sphincter deficiency
      completed this study. Multichannel urodynamic testing was performed
      preoperatively and 6 weeks postoperatively. Maximum urethral closure pressure and
      pressure transmission ratio were recorded. Valsalva leak point pressures were
      determined at 150 mL and at full bladder capacity. Resting and straining urethral
      angles were measured using the cotton swab technique. Subjects completed both the
      Incontinence Impact Questionnaire and Urodynamic Distress Inventory
      preoperatively and postoperatively. RESULTS: Thirty-five consecutive women were
      studied. Twenty-three (65.7%) had a preoperative diagnosis of intrinsic sphincter
      deficiency as defined by maximum urethral closure pressure less than 20 cm H(2)O
      and/or Valsalva leak point pressure less than 60 cm H(2)O. Subjective and
      objective success rates were 91% and 83%, respectively. Subjects showed an 86.8%
      (95% CI 71.9%, 100.0%) improvement in their Incontinence Impact Questionnaire
      score and a 72.9% (95% CI 62.6%, 83.1%) improvement in their Urodynamic Distress
      Inventory score. The mean change in maximum urethral closure pressure was -1.3 cm
      H(2)O (95% CI -5.9, 3.3), whereas the pressure transmission ratio increased 15.7%
      (95% CI 5.0%, 26.3%). The mean decrease in straining urethral angle was 16.3
      degrees (95% CI -23.9 degrees, -8.7 degrees ). Cured subjects demonstrating
      hypermobility preoperatively continued to do so postoperatively. CONCLUSION:
      There was a significant increase in pressure transmission ratio, but not maximum
      urethral closure pressure, after TVT. These changes are similar to those reported
      after retropubic urethropexy and traditional sling procedures. The effectiveness
      of the TVT sling does not appear to depend on a clinically significant change in
      the straining urethral angle.

PMID- 11576582
TI  - Cost of pelvic organ prolapse surgery in the United States.
AB  - OBJECTIVE: To estimate the annual direct cost to society of pelvic organ prolapse
      operations in the United States. METHODS: We multiplied the number of pelvic
      organ prolapse operations identified in the 1997 National Hospital Discharge
      Survey by national average Medicare reimbursement for physician services and
      hospitalizations. Although this reimbursement does not estimate the actual cost,
      it is a proxy for cost, which estimates what society pays for the procedures.
      RESULTS: In 1997, direct costs of pelvic organ prolapse surgery were 1012 million
      dollars (95% confidence interval [CI] 775 dollars, 1251 million), including 494
      dollars million (49%) for vaginal hysterectomy, 279 million dollars (28%) for
      cystocele and rectocele repair, and 135 million dollars (13%) for abdominal
      hysterectomy. Physician services accounted for 29% (298 million dollars) of total
      costs, and hospitalization accounted for 71% (714 million dollars). Twenty-one
      percent of pelvic organ prolapse operations included urinary incontinence
      procedures (218 million dollars). If all operations were reimbursed by non
      Medicare sources, the annual estimated cost would increase by 52% to 1543 million
      dollars. CONCLUSION: The annual direct costs of operations for pelvic organ
      prolapse are substantial.

PMID- 11576583
TI  - Should we allow a trial of labor after a previous cesarean for dystocia in the
      second stage of labor?
AB  - OBJECTIVE: To estimate the rate of successful vaginal birth including operative
      vaginal delivery in patients with a previous cesarean for cephalopelvic
      disproportion in the second stage of labor. METHODS: Data from all patients who
      underwent trial of labor after a previous cesarean between 1990 and 2000 at our
      tertiary care institution were analyzed. Medical records were reviewed and data
      collected for the following variables: indication for the previous cesarean,
      birth weight and cervical dilatation at previous cesarean delivery, as well as
      the mode of delivery (spontaneous, vacuum, forceps, cesarean) and the birth
      weight for the subsequent pregnancy. Pearson's chi(2) test and one-way analysis
      of variance were used for statistical analyses. RESULTS: There were 2002 patients
      included in the study. Two hundred fourteen (11%) had their previous cesarean for
      dystocia in the second stage of labor, 654 (33%) for dystocia in the first stage
      of labor, and 1134 (57%) for other indications. The vaginal birth after cesarean
      success rate was 75.2% (P = .015 vs other indications), 65.6% (P < .001 vs other
      indications), and 82.5%, respectively. The rate of operative vaginal delivery was
      15%, 12%, and 10% (P = .109). CONCLUSION: A trial of labor is reasonable in women
      whose previous cesarean was for dystocia in the second stage of labor. In this
      series, patients who underwent a trial of labor after a previous cesarean for
      dystocia in the second stage had 75.2% (95% confidence interval 69.5, 81.0)
      chance of achieving vaginal delivery.

PMID- 11576584
TI  - Longitudinal analysis of bacterial vaginosis: findings from the HIV epidemiology
      research study.
AB  - OBJECTIVE: To determine the natural history of bacterial vaginosis in women with
      or at risk for human immunodeficiency virus (HIV). METHODS: A cohort of 854 HIV
      infected women and 434 HIV-uninfected women from four US sites was followed
      prospectively with gynecologic exams every 6 months over a 5-year period. The
      prevalence, incidence, persistence, and severity of bacterial vaginosis, which
      was defined using a Gram-staining scoring system, were calculated using
      generalized estimating equation methods. RESULTS: In adjusted analyses, HIV
      infected women had a higher prevalence of bacterial vaginosis than HIV-uninfected
      women (adjusted odds ratio [OR] 1.29; 95% confidence interval [CI] 1.08, 1.55).
      Although HIV-infected women were not more likely to have incident infections,
      they were more likely to have persistence of their infections (adjusted OR 1.49;
      95% CI 1.18, 1.89). Similarly, immunocompromised women (CD4+ cell count less than
      200 cells/microL) were more likely than HIV-infected women with higher CD4+ cell
      counts (more than 500 cells/microL) to have prevalent (adjusted OR 1.29; 95% CI
      1.03, 1.60) and persistent (adjusted OR 1.38; 95% CI 1.01, 1.91) bacterial
      vaginosis infections, but not more likely to have incident infections.
      Immunocompromised women had more severe bacterial vaginosis by both clinical
      criteria (adjusted OR 1.40; 95% CI 1.08, 1.82) and by Gram-staining criteria
      (adjusted OR 1.50; 95% CI 1.12, 2.00). CONCLUSIONS: Bacterial vaginosis is more
      prevalent and persistent among HIV-infected women, particularly among those who
      are immunocompromised. Immunocompromised women are more likely than HIV-infected
      women with higher CD4+ cell counts to have severe bacterial vaginosis.

PMID- 11576585
TI  - Tryptophan hydroxylase gene polymorphism (A218C) and idiopathic recurrent
      miscarriage.
AB  - OBJECTIVE: To investigate the frequency of a polymorphism in intron 7 of the
      tryptophan hydroxylase gene among women with idiopathic recurrent miscarriage and
      healthy controls. METHODS: In a case control study, we studied 125 women with a
      history of three or more consecutive pregnancy losses before 20 weeks' gestation
      and 137 healthy controls with at least two live births and no history of
      pregnancy loss. Peripheral venous puncture, DNA extraction, and polymerase chain
      reaction followed by restriction fragment length polymorphism analysis were used
      to genotype women for the presence of the A218C polymorphism in intron 7 of the
      tryptophan hydroxylase gene. RESULTS: Allele frequencies among women with
      idiopathic recurrent miscarriage and controls were 32.4% and 38.7%, respectively,
      for allele A (wild type) and 67.6% and 61.3%, respectively, for allele C
      (mutant). No association between the presence of allele C and idiopathic
      recurrent miscarriage was found (P = .3; odds ratio 1.31; 95% confidence interval
      0.93, 1.87). Genotype frequencies also were not significantly different between
      the study group (C/C: 44.8%; A/C: 45.6%; A/A: 9.6%) and the control group (C/C:
      37.2%; A/C: 48.2%; A/A: 14.6%; P = .2). Between women with primary and women with
      secondary idiopathic recurrent miscarriage, no statistically significant
      differences with respect to allele frequencies were observed (63% vs 62% for
      allele C and 31% vs 38% for allele A; P = .3). CONCLUSION: The A218C polymorphism
      in intron 7 of the tryptophan hydroxylase gene is not associated with idiopathic
      recurrent miscarriage.

PMID- 11576586
TI  - Macrophage secretory products and sperm zona pellucida binding.
AB  - OBJECTIVE: To determine if exposure of human gametes to macrophage secretory
      products reduces sperm binding to the zona pellucida, and to determine which
      cytokine(s) may be responsible for this effect. METHODS: A human macrophage cell
      line was cultured and either activated with lipopolysaccharide for 2 hours and
      then washed or left unactivated. Culture-conditioned media from activated or
      unactivated cells was used in hemizona assay. Hemizonae were incubated with sperm
      suspended in culture medium from either unactivated macrophages or activated
      macrophages, with the matching hemizona incubated with sperm suspended in control
      medium. Matching hemizonae were incubated with sperm suspended in unactivated
      macrophage medium paired with sperm suspended in activated macrophage culture
      medium. Conditioned medium from activated macrophages was found to have elevated
      levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, and
      transforming growth factor-beta, therefore, gametes were also exposed to these
      cytokines followed by the hemizona assay. After each incubation, the number of
      sperm tightly bound to the outer surface of each hemizona was determined.
      RESULTS: Exposure of gametes to activated and unactivated macrophage culture
      conditioned media significantly decreases sperm binding to the zona pellucida,
      with medium from activated macrophages inducing the greatest effect (P < .05).
      Exposure of sperm to TNF-alpha significantly impaired sperm binding (P < .05),
      whereas other cytokines tested had no effect. CONCLUSION: These results suggest
      that macrophage secretory products in the basal and activated state may be a
      factor in endometriosis-associated infertility through the interference of sperm
      binding to the zona pellucida, and that TNF-alpha is a key cytokine responsible
      for this effect.

PMID- 11576587
TI  - Management choice and adherence to follow-up after colposcopy in women with
      cervical intraepithelial neoplasia 1.
AB  - OBJECTIVE: To determine women's preference when given a choice of management
      between cryotherapy and cytology surveillance and to compare subsequent adherence
      to serial cytologic follow-up after being diagnosed with cervical intraepithelial
      neoplasia grade 1 (CIN1). METHODS: Two hundred nineteen low-income women with
      biopsy-proven CIN1 seen in a reproductive health clinic from August 1995 through
      December 1999 were offered cryotherapy or cytology surveillance, followed by
      cytologic testing every 4 months until three consecutive results were normal.
      Endpoints of the study were: successful completion of follow-up; transferred or
      referred out of clinic; or lost to follow-up. RESULTS: Ninety-four women (42.9%)
      chose cryotherapy, compared with 125 women (57.1%) who chose cytology
      surveillance (P < .05). Cryotherapy patients were more likely to return for at
      least one visit (their treatment visit) after colposcopy compared with cytology
      surveillance patients (P < .001). In contrast to their initial return for
      treatment of 98.9%, cryotherapy patients were less likely to return for their
      first follow-up cytology visit compared to surveillance-only patients (68.1% and
      83.2%, respectively, P < .01). Thirty-seven percent of the total group
      successfully completed follow-up at the clinic, 30.1% transferred or were
      referred, and 32.9% were lost to follow-up. CONCLUSION: Successful completion of
      a commonly recommended protocol for serial cytology follow-up was low. Management
      choice affected initial adherence but not adherence to long-term follow-up.

PMID- 11576588
TI  - Recurrence of invasive cervical carcinoma more than 5 years after initial
      therapy.
AB  - OBJECTIVE: To estimate the probability of and risk factors for the recurrence of
      invasive cervical carcinoma over 5 years after initial therapy. METHODS: Patients
      (n = 827) with invasive cervical carcinoma were treated and received follow-up
      care for up to 29 years. Late recurrence was defined as recurrence more than 5
      years after initial therapy. The probability of late recurrence was evaluated in
      terms of clinical stage, histologic type, and type of initial therapy. RESULTS:
      Late recurrence was seen in 21 of 569 patients who had survived 5 years (3.7%).
      Recurrence rates were 1.8% (six of 331) in stage I, 5.2% (eight of 154) in stage
      II, 8.6% (seven of 81) in stage III, and 0% (none of three) in stage IV. The
      probability of late recurrence in patients with stage I disease was significantly
      lower than that in stage II and stage III diseases (stage I compared with stage
      II, P = .038, stage I compared with stage III, P = .002). Late recurrence
      occurred in 21 (3.8%) of 547 cases of squamous cell carcinoma, whereas no late
      recurrences were found in 22 cases of adenocarcinoma. The late recurrence rate in
      patients who received radiation (7.1%, 17 of 241) was significantly higher than
      that in patients who received surgery (1.2%, four of 328; P = .001). CONCLUSION:
      Patients with uterine cervical squamous cell carcinoma, especially those with
      stage II or stage III diseases who received radiation therapy as initial
      treatment, warrant annual follow-up care beyond the standard 5 years after
      initial therapy.

PMID- 11576589
TI  - An odd measure of risk: use and misuse of the odds ratio.
AB  - OBJECTIVE: To determine how often the odds ratio, as used in clinical research of
      obstetrics and gynecology, differs substantially from the risk ratio estimate and
      to assess whether the difference in these measures leads to misinterpretation of
      research results. METHODS: Articles from 1998 through 1999 in Obstetrics &
      Gynecology and the American Journal of Obstetrics and Gynecology were searched
      for the term "odds ratio." The key odds ratio in each article was identified,
      and, when possible, an estimated risk ratio was calculated. The odds ratios and
      the estimated risk ratios were compared quantitatively and graphically. RESULTS:
      Of 151 studies using odds ratios, 107 were suitable to estimate a risk ratio. The
      difference between the odds ratio and the estimated risk ratio was greater than
      20% in 47 (44%) of these articles. An odds ratio appears to magnify an effect
      compared with a risk ratio. In 39 (26%) articles the odds ratio was interpreted
      as a risk ratio without explicit justification. CONCLUSION: The odds ratio is
      frequently used, and often misinterpreted, in the current literature of
      obstetrics and gynecology.

PMID- 11576591
TI  - Lethal pulmonary hypoplasia after in-utero myelomeningocele repair.
AB  - BACKGROUND: In-utero surgical repair of fetal myelomeningocele has been performed
      as a means to improve the postnatal condition of affected infants. CASE: A
      nulliparous woman underwent in-utero surgical repair of a fetal lumbosacral
      myelomeningocele at 24 weeks' gestation. Her postoperative convalescence was
      complicated by pulmonary edema, abdominal pain, chronic oligohydramnios, and
      preterm labor. The infant was delivered by cesarean at 33 weeks' gestation, but
      expired from respiratory distress caused by pulmonary hypoplasia at 9 hours of
      age. CONCLUSION: Until the benefits of in-utero repair of fetal myelomeningoceles
      are determined by well-controlled clinical trials, this technique remains
      investigational. Physicians and their patients who are considering this procedure
      must be fully aware of the potential risks that can occur.

PMID- 11576590
TI  - Toward the ethical evaluation and use of maternal-fetal surgery.
AB  - BACKGROUND: Important clinical, social, and ethical questions are associated with
      the evaluation and use of surgical approaches aimed at correcting fetal anatomic
      abnormalities. In particular, the expansion of maternal-fetal surgery to
      ameliorate nonlethal fetal conditions has intensified the need to address issues
      about the adequacy of technology assessment and the safety of those who undergo
      these novel procedures. APPROACH: After discussions at a multidisciplinary
      conference, we reviewed the development and current practices of maternal-fetal
      surgery and analyzed the relevant ethical issues concerning the use of maternal
      fetal surgery for nonlethal conditions, focusing on the correction of
      myelomeningocele. FINDINGS: Characterizing nonvalidated maternal-fetal surgery
      procedures as "innovative therapy" blurs the boundaries between research and
      therapy and creates uncertainty about the obligations of clinicians and
      researchers. Further, maternal-fetal surgery raises ethical issues related to
      maternal risks and benefits, informed consent, distinguishing lethal from
      nonlethal conditions, withholding unproven treatments, entrepreneurship, and
      prioritization. RECOMMENDATIONS: To help ensure that maternal-fetal surgery will
      be studied and eventually applied in a scientifically and ethically sound manner,
      we offer several recommendations. First, innovation in maternal-fetal surgery
      should be conducted and evaluated as research. Second, women must be considered
      research subjects in these trials. Third, the informed consent process must
      ensure adequate comprehension and genuine voluntariness in those considering
      participation. Fourth, discriminatory and fearful attitudes toward individuals
      with disabilities should be addressed explicitly prior to making a decision to
      proceed with maternal-fetal surgery in an attempt to correct such disabilities.
      Fifth, maternal-fetal surgery should not be performed for cosmetic indications
      unless and until there is reliable evidence that maternal-fetal surgery can be
      performed safely and that long-term side effects on women and their offspring are
      minimal. Sixth, centers of excellence should be established for conducting
      research and providing maternal-fetal surgery. Seventh, funding for research on
      maternal-fetal surgery should be considered in the context of societal needs.

PMID- 11576593
TI  - Cardiac glycosides from Cryptostegia grandiflora.
AB  - From the leaves of Cryptostegia grandiflora, four new cardiac glycosides
      oleandrigenin 3-O-beta-glucopyranosyl-(1-->4)-beta-cymaropyranosyl-(1-->4)-beta
      digitoxopyranoside, cryptostigmin I, oleandrigenin 3-O-beta-glucopyranosyl-(1-
      >4)-alpha-rhamnopyranoside, cryptostigmin II, 16-propionylgitoxigenin 3-O-beta
      glucopyranosyl-(1-->4)-alpha-rhamnopyranoside, cryptostigmin III and
      oleandrigenin 3-O-beta-glucopyranosyl-(1-->6)-beta-glucopyranosyl-(1-->4)-beta
      cymaropyranosyl-(1-->4)-beta-digitoxopyranoside, cryptostigmin IV have been
      isolated together with two known cardenolides subalpinosid and 16-O-acetyl
      digitalinum verum. The structures of the isolated compounds were verified by
      means of MS and NMR spectral analyses.

PMID- 11576594
TI  - Enmein type diterpenoids from Isodon japonica.
AB  - Two enmein type diterpenoids, taibaijaponicains A and B, were isolated from the
      ethanol extract of the leaves and branches of Isodon japonica. Their structures
      are designated as 6beta,11alpha-dihydroxy-16alpha-methoxymethyl-6,20-epoxy-6,7
      seco-ent-kaur-15-one-1,7-olide and 3beta-acetoxy-6beta,11alpha-dihydroxy-16alpha
      methoxymethyl-6,20-epoxy-6,7-seco-ent-kaur-15-one-1,7-olide, respectively, on the
      basis of detailed spectroscopic analyses.

PMID- 11576595
TI  - Essential oil analysis of 10 Piperaceae species from the Brazilian Atlantic
      forest.
AB  - The volatile composition of ten Piperaceae species, comprising three genera
      (Ottonia, Piper and Peperomia) has been studied. The species were collected in a
      typical fragment of the Brazilian Atlantic forest, constantly being damaged by
      human action. The essential oils were obtained by hydrodistillation in a modified
      Clevenger-type apparatus and their analyses were performed by GC and GC/MS.
      Identification of the substances was made by comparison of mass spectra and
      retention indices with literature records. A great number of non-oxygenated
      monoterpenes and sesquiterpenes were identified. Most of these sesquiterpenes are
      derived from E,E-farnesyl-PP, suggesting a preference of these species to
      synthesize metabolites from this pathway. Arylpropanoids, although being common
      compounds produced by Piperaceae species, were not found in these oils.

PMID- 11576596
TI  - Bacopaside I and II: two pseudojujubogenin glycosides from Bacopa monniera.
AB  - Two saponins, designated as bacopaside I and II, have been isolated from Bacopa
      monniera Wettst. and their structures have been elucidated as 3-O-alpha-L
      arabinofuranosyl-(1-->2)-[6-O-sulphonyl-beta-D-glucopyranosyl-(1-->3)]-alpha-L
      arabinopyranosyl pseudojujubogenin (1) and 3-O-alpha-L-arabinofuranosyl-(1-->2)
      [beta-D-glucopyranosyl (1-->3)]-beta-D-glucopyranosyl pseudojujubogenin (2)
      mainly on the basis of 2D NMR and other spectral analyses.

PMID- 11576597
TI  - Bufadienolides from Drimia robusta and Urginea altissima (Hyacinthaceae).
AB  - The bufadienolides, 6beta-acetoxy-3beta,8beta,12beta,14beta-tetrahydroxybufa
      4,20,22-trienolide (12beta-hydroxyscillirosidin) (1) and 14beta-hydroxybufa
      4,20,22-trienolide 3beta-O-[alpha-L-rhamnopyranosyl-[(1-->4)-beta-D
      glucopyranosyl]-(1-->3)-alpha-L-rhamnopyranoside] (urginin) (2) were isolated
      from Drimia robusta and Urginea altissima, respectively.

PMID- 11576598
TI  - Biflavonoids from the aerial part of Stephania tetrandra.
AB  - Investigation of the aerial part of Stephania tetrandra led to the isolation of
      two biflavonoids, stephaflavone A and stephaflavone B, with a 3-6" linkage
      pattern, together with beta-sitosterol. Their structures were established on the
      basis of their spectroscopic data and their physicochemical properties.

PMID- 11576599
TI  - A cytotoxic diarylheptanoid from Viscum cruciatum.
AB  - A diarylheptanoid, 1,7-di-(3',4'-dihydroxyphenyl)-4-hepten-3-one, hirsutanone,
      has been isolated from the methanolic extract of the aerial parts of Viscum
      cruciatum (Viscaceae) and characterized by spectroscopic methods and chemical
      transformations. This compound showed cytotoxic activity against melanoma (UACC
      62), renal (TK-10) and breast (MCF-7) cancer cell lines.

PMID- 11576600
TI  - Cytotoxic coumarins from Calophyllum dispar.
AB  - Six coumarins have been isolated from the fruits and the stem bark of Calophyllum
      dispar (Clusiaceae). The structures of these minor components were established by
      means of spectroscopic analysis, including extensive 2D NMR studies. Some of
      these coumarins exhibited a significant cytotoxic activity against KB cells.

PMID- 11576601
TI  - Flavonol glycosides from the stems of Trigonella foenum-graecum.
AB  - Two kaempferol glycosides [kaempferol 3-O-beta-D-glucosyl(1-->2)-beta-D
      galactoside 7-O-beta-D-glucoside and kaempferol 3-O-beta-D-glucosyl(1-->2)-(6"-O
      acetyl)-beta-D-galactoside 7-O-beta-D-glucoside] as well as the quercetin
      glycoside [quercetin 3-O-beta-D-glucosyl(1-->2)-beta-D-galactoside 7-O-beta-D
      glucoside] were isolated from the stems of Trigonella foenum-graecum L.
      (Leguminosae) along with a known kaempferol glycoside, lilyn [kaempferol 3-O-beta
      D-glucosyl(1-->2)-beta-D-galactoside]. Their structures were established by
      analysis of chemical and spectral evidence.

PMID- 11576602
TI  - Phenanthrene derivatives from the orchid Coelogyne cristata.
AB  - Coeloginanthridin, a 9,10-dihydrophenanthrene derivative, and coeloginanthrin,
      the corresponding phenanthrene analogue, were isolated from the orchid Coelogyne
      cristata which earlier afforded coelogin (1a) and coeloginin (1b). The structures
      of coeloginanthridin and coeloginanthrin were established as 3,5,7-trihydroxy-1,2
      dimethoxy-9,10-dihydrophenanthrene (2a) and 3,5,7-trihydroxy-1,2
      dimethoxyphenanthrene (2c), respectively, from spectral and chemical evidence
      including the conversion of coeloginanthridin triacetate (2b) to coeloginanthrin
      triacetate (2d) by dehydrogenation with DDQ. In the light of earlier reports on
      structurally similar compounds, 2a and 2c may have biological activities of
      phytoalexins and endogenous plant growth regulators.

PMID- 11576603
TI  - An oligomer from flaxseed composed of secoisolariciresinoldiglucoside and 3
      hydroxy-3-methyl glutaric acid residues.
AB  - A straight-chain oligomeric structure composed of five
      secoisolariciresinoldiglucoside (SDG) residues interconnected by four 3-hydroxy-3
      methyl glutaric acid (HMGA) residues (molecular weight ca. 4000 Da) was assigned
      to the main lignan of flaxseed on the basis of nuclear magnetic resonance
      spectroscopy (NMR).

PMID- 11576604
TI  - Stilbenoids from the lianas of Gnetum pendulum.
AB  - Two stilbenoids, gnetupendin A and B, were isolated from the lianas of Gnetum
      pendulum C. Y. Cheng, together with four known compounds, resveratrol,
      isorhapontigenin, shegansu B and beta-daucosterol. Their structures were
      determined on the basis of analysis of spectral evidence, especially 2D NMR
      spectroscopic techniques.

PMID- 11576606
TI  - A weakly antimalarial biflavanone from Rhus retinorrhoea.
AB  - The biflavanone (2S,2"S)-7,7"-di-O-methyltetrahydroamentoflavone and five known
      flavonoids, 7-O-methylnaringenin, 7,3'-O-dimethylquercetin, 7-O-methylapigenin, 7
      O-methylluteolin, and eriodictyol were isolated from the leaves of Rhus
      retinorrhoea Steud, Ex Olive. The biflavanone exhibited moderate antimalarial
      activity with IC50 0.98 microg/ml against Plasmodium falciparum (W2 Clone) and
      weak activity against P. falciparum (D6 Clone) with IC50 2.8 microg/ml.
      Nevertheless, it did not display any cytotoxicity. 7-O-Methylnaringenin showed
      weak antimicrobial activity against Candida albicans, C. krusei, Staphylococcus
      aureus, Mycobacterium smegmatis, M. intracellulare, and M. xenopi with MIC
      approximately 100 microg/ml. Characterization of each compound was based on
      spectral analysis and comparison with reported data.

PMID- 11576605
TI  - Flavonoids from Glycyrrhiza pallidiflora hairy root cultures.
AB  - Glycyrrhiza pallidiflora hairy roots were induced from axenic young plants by
      direct infection with Agrobacterium rhizogenes. The chemical constituents were
      then investigated after mass culture. The isoflavone, licoagroisoflavone and the
      coumestan, licoagroside C, were isolated along with seven known flavonoids. Their
      structures were determined on the basis of spectroscopic evidence.

PMID- 11576607
TI  - Phenanthropyran derivatives from Phalaenopsis equestris.
AB  - Two phenanthropyran derivatives, 3-methoxy-2,7-dihydroxy-5H-phenanthro[4,5
      bcd]pyran and 2,3,7-trihydroxy-5H-phenanthro[4,5-bcd]pyran were isolated from the
      orchid Phalaenopsis equestri. Their chemical structures were elucidated from
      spectroscopic (NMR, MS etc.) analyses.

PMID- 11576608
TI  - Flavone C-glycosides from Scleranthus uncinatus.
AB  - Two flavone C-glycosides, 5,7,4'-trihydroxy-3'-methoxyflavone-8-C-beta-D
      xylopyranoside-2"-O-glucoside, 5,7-dihydroxy-3'-methoxy-4'-acetoxyflavone-8-C
      beta-D- xylopyranoside-2"-O-glucoside and one known maltol beta-D-glucopyranoside
      were isolated for the first time from the Scleranthus uncinatus and their
      structures deduced by high field 1D and 2D 400 MHz NMR and (+) FAB-MS spectra.

PMID- 11576609
TI  - Polyphenols from Cornulaca monacantha.
AB  - The aerial parts of the Egyptian herb Cornulaca monacantha have yielded two new
      galloyltannin analogs (named monacanthin A and monacanthin B) characterized by
      protoctechuoyl moiety at C-6, and also a new flavonol glycoside, quercetin-4'-O
      beta-D-galactoside. The structures of the new compounds were established by
      conventional analytical methods and confirmed by spectral analyses. Two known
      flavonoids, luteolin-7-O-rhamnoside, luteolin-7-O-glucoside, and two known
      gallotannins, penta-O-galloyl-beta-D-glucose and 1,2,3,6-tetra-O-galloyl-beta-D
      glucose were also isolated.

PMID- 11576610
TI  - Phenylpropanoid glucosides from Chrozophora obliqua.
AB  - From the aerial parts of Chrozophora obliqua, two phenylpropanoid glucosides: 4-O
      methyl guaiacylglycerol 9-O-beta-glucopyranoside (1) and 4-O-methyl
      guaiacylglycerol 8-O-beta-glucopyranoside (2) together with syringin, benzyl
      alcohol glucoside, isorhamnetin-3-O-beta-glucopyranoside-7-O-alpha
      rhamnopyranoside and quercetin-3-O-beta-glucopyranoside-7-O-alpha
      rhamnopyranoside have been isolated. The structures of the isolated compounds
      were verified by means of MS and NMR spectral analyses.

PMID- 11576612
TI  - Indolopyridoquinazoline alkaloid from Leptothyrsa sprucei.
AB  - The indolopyridoquinazoline alkaloid, 3-hydoxyrutaecarpine, was isolated from
      Leptothyrsa sprucei, along with 8-methoxypsoralen, 5-methoxypsoralen,
      imperatorin, isoimperatorin, kaempferol 3-O-alpha-L-rhamnopyranoside, clematine
      and cnidioside B. The usefulness of the gradient 1H-15N HMBC NMR spectroscopy in
      the structure elucidation of 3-hydroxyrutaecarpine is noted.

PMID- 11576611
TI  - 5',6'-dehydroguiachrysine and 5',6'-dehydroguiaflavine, two curarizing quaternary
      indole alkaloids from the stem bark of Strychnos guianensis.
AB  - Two new quaternary indole alkaloids 5',6'-dehydroguiachrysine (1) and 5',6'
      dehydroguiaflavine (2) were isolated from Strychnos guianensis stem bark. Their
      structures were determined by analysis of spectral data. Their inhibitory effects
      on neuromuscular transmission are also reported and compared to that of other
      quaternary alkaloids.

PMID- 11576613
TI  - Quinones from Heliotropium ovalifolium.
AB  - Two new benzoquinones, heliotropinones A and B, have been isolated from the
      aerial parts of Heliotropium ovalifolium. Their structures were elucidated by
      spectrometric methods including high resolution electrospray ionization (ESI-HR),
      EI mass spectrometry, 1H, 13C and 2D NMR experiments. The two quinones
      demonstrated antifungal activities against Cladosporium cucumerinum and Candida
      albicans as well as antibacterial activity against Bacillus subtilis.

PMID- 11576614
TI  - Benzoxazinoid glucosides from Acanthus ilicifolius.
AB  - From the aerial parts of Acanthus ilicifolius, two benzoxazinoid glucosides, 7
      chloro-(2R)-2-O-beta-D-glucopyranosyl-2H-1,4-benzoxazin-3(4H)-one and (2R)-2-O
      beta-D-glucopyranosyl-5-hydroxy-2H-1,4-benzoxazin-3(4H)-one have been isolated,
      together with six known compounds. The structural elucidations were based on the
      analyses of spectroscopic data.

PMID- 11576615
TI  - Glucides of Cnidium monnieri fruit.
AB  - From the fruit of Cnidium monnieri Cusson (Umbelliferae), two glucides were
      isolated together with other known glucides. Their structures were clarified as
      glycerol 2-O-alpha-L-fucopyranoside and D-quinovitol (6-deoxy-D-glucitol),
      respectively.

PMID- 11576616
TI  - Glycosides and xanthine oxidase inhibitors from Conyza bonariensis.
AB  - Fractionation of the xanthine oxidase inhibitory methanol extract of Conyza
      bonariensis afforded three glycosides, in addition to nine known compounds
      including amyrin, beta-sitostero1 daucosterol, syringic acid 3-hydroxy-5
      methoxybenzoic acid, eugenol 4-O-glucopyranoside, and luteolin, apigenin and
      takakin 8-O-glucuronide. The structures of the glycosides were established by a
      combination of spectroscopic methods (IR, MS, 1H and 13C NMR, DEPT, COSY, HMQC
      and HMBC) as 4-hydroxypyridin-3-carboxylic acid 4-O-glucopyranoside, 8-hydroxy
      6,7-dihydrolinalool 8-O-glucopyranoside and bonaroside [viz. 1,3,4,12
      tetrahydroxy-2-(9-hexadecenoylamino)octadecane 1-O-glucopyranoside]. The in vitro
      enzyme assay showed that syringic acid and takakin 8-O-glucuronide displayed weak
      inhibitory activity against xanthine oxidase with IC50 values of 500+/-41 microM
      and 170+/-12 microM, respectively.

PMID- 11576617
TI  - Sesquiterpenes and alkaloids from Scorodocarpus borneensis.
AB  - A new sesquiterpene, scodopin, and a mixture of three tryptamine-type alkaloids,
      scorodocarpines A-C, were isolated from the fruits of Scorodocarpus borneensis,
      together with a known hemisynthetic sesquiterpene, cadalene-beta-carboxylic acid,
      which was isolated from the bark. The structures of the new compounds were
      elucidated by interpretation of spectral data, especially tandem mass
      spectrometry for the alkaloid mixture.

PMID- 11576619
TI  - Substrate interaction with 5alpha-reductase enzyme: influence of the 17beta-chain
      chirality in the mechanism of action of 4-azasteroid inhibitors.
AB  - A series of steroidal compounds were synthesized in order to evaluate the
      possible influence of the configuration of a stereocenter in the 17beta-side
      chain on the inhibitory activity on the enzyme 5alpha-reductase (5AR). For this
      purpose diastereomerically pure 4-azasteroids epimers at C-22 were prepared
      (compounds 1-11) and tested as inhibitors of 5AR in "in vitro" tests. The
      obtained data showed that in most cases the couples of epimers possess a
      significant difference in their biological activity. We also considered, for the
      tested molecules, a series of chemico-physical parameters in order to find a
      possible correlation with their biological activity. The findings allowed us to
      propose a model of the binding site of 5AR which comprises also, for 4-azasteroid
      inhibitors, the configurational aspect of the 17beta-side chain.

PMID- 11576618
TI  - Hydrolysis of conjugated steroids by the combined use of beta-glucuronidase
      preparations from helix pomatia and ampullaria: determination of urinary cortisol
      and its metabolites.
AB  - This study describes the enzymatic hydrolysis of urinary conjugates of cortisol,
      cortisone, tetrahydrocortisol, allotetrahydrocortisol, and tetrahydrocortisone
      with beta-glucuronidase preparations from Helix pomatia and Ampullaria. The
      objective of the present studies was to find optimal hydrolysis conditions for
      these conjugated steroids. Assay of the isolated steroids was carried out by GC
      MS using deuterium-labeled compounds as internal standards. The
      allotetrahydrocortisol conjugate was clearly the hardest to hydrolyze with enzyme
      from Helix pomatia and required increased enzyme concentration and prolonged
      incubation. Hydrolysis of a urine sample for 2.0 h with the simultaneous use of
      3400 units/ml Ampullaria and 5400 units/ml Helix pomatia enzymes in 0.5 M acetate
      buffer at 55 degrees C achieved more complete cleavage of the urinary conjugates
      of the five steroids examined. It is thus advantageous to use the Ampullaria and
      Helix pomatia enzymes in combination to obtain the highest yield in the urinary
      corticosteroid assay.

PMID- 11576620
TI  - Synthesis and analgesic effects of kyotorphin-steroid linkers.
AB  - Kyotorphin (KTP, H-Tyr-Arg-OH) was covalently bonded with hydrocortisone or
      estrone to form the corresponding hydrocortisone-21-O-yl-succinyl-Tyr-ArgOH or
      estrone-3-O-yl-acyl-Tyr-Arg-OH. Their analgesic activities were investigated
      using the tail flick test. The potency of the two linkers were significantly
      higher than that of KTP and the mixture of KTP and hydrocortisone or estrone in
      the CNS and/or the periphery administration.

PMID- 11576621
TI  - Effect of glucocorticoid excess on the cortisol/cortisone ratio.
AB  - OBJECTIVE: The conversion of cortisol, which binds avidly to the
      mineralocorticoid receptor, to cortisone, which no longer has mineralocorticoid
      function, is predominantly catalyzed by the 11beta-hydroxysteroid dehydrogenase
      type 2 (11beta-HSD 2). It was the objective of the present study to examine the
      impact of different forms of glucocorticoid excess on the cortisol/cortisone
      ratio and to differentiate their role in the genesis of hypertension. DESIGN AND
      METHODS: Plasma cortisol and cortisone levels were determined in 12 adults with
      Cushing's disease, 12 adults with hypercortisolism due to an adrenal tumor, and
      20 healthy volunteers before and after an intravenous ACTH test, using specific
      radioimmunoassays after automated Sephadex LH 20 chromatography. RESULTS: The
      cortisol/cortisone ratios were significantly higher in patients with Cushing's
      disease (13.9 +/- 1.1), adrenal tumors (11.5 +/- 2.3), and in healthy volunteers
      after ACTH stimulation (14.1 +/- 2.0) than in untreated controls (6.0 +/- 0.5) (P
      < 0.001, P < 0.05, and P < 0.001, respectively). Similar differences were seen
      for cortisol plasma concentrations, whereas cortisone concentrations did not
      differ among the groups. CONCLUSIONS: Our data suggest that the excessive
      mineralocorticoid effects in patients with hypercortisolism are inflicted by
      elevated cortisol/cortisone ratios possibly due to an insufficient conversion of
      cortisol to cortisone by 11beta-HSD 2. This may provide a possible explanation
      for the occurrence of hypertension. This effect seems to be independent of the
      role of ACTH in the mechanism of hypercortisolism.

PMID- 11576622
TI  - Chemical synthesis of 16beta-propylaminoacyl derivatives of estradiol and their
      inhibitory potency on type 1 17beta-hydroxysteroid dehydrogenase and binding
      affinity on steroid receptors.
AB  - The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) are members of a family of
      enzymes that catalyze the interconversion of weakly active sexual hormones
      (ketosteroids) and potent hormones (17beta-hydroxysteroids). Among the known
      isoforms of 17beta-HSD, the type 1 catalyzes the NAD(P)H-mediated reduction of
      estrone (E(1)) to estradiol (E(2)), a predominant mitogen for the breast cancer
      cells. Therefore, the inhibition of this particular enzyme is a logical approach
      to reduce the concentration of estradiol in breast tumors. To develop inhibitors
      of type 1 17beta-HSD activity, we hypothesized that molecules containing both
      hydrophobic and hydrophilic components should be interesting candidates for
      interacting with both the steroid binding domain and some amino acid residues of
      the cofactor binding domain of the enzyme. Firstly, a conveniently protected
      16beta-(3-aminopropyl)-E(2) derivative was synthesized from commercially
      available E(1). Then, a representative of all class of NHBoc-protected amino
      acids (basic, acid, aromatic, aliphatic, hydroxylated) were coupled using
      standard procedures to the amino group of the precursor. Finally, cleavage of all
      protecting groups was performed in a single step to generate a series of 16beta
      propylaminoacyl derivatives of E(2). The enzymatic screening revealed that none
      of the novel compounds can inhibit the reductive activity of type 1 17beta-HSD.
      On the other hand, all of these E(2) derivatives did not show any significant
      binding affinity on four steroid receptors including the estrogen receptor.
      Additional efforts aimed at improving the inhibitory potency of these steroidal
      derivatives on type 1 17beta-HSD without providing estrogenic activities is under
      investigation using a combinatorial chemistry approach.

PMID- 11576623
TI  - Configurational analysis and relative binding affinities of 16-methyl-5alpha
      androstane derivatives.
AB  - The four possible isomers 16beta-hydroxymethyl-5alpha-androstane-3beta,17beta
      diol 1, 16alpha-hydroxymethyl-5alpha-androstane-3beta,17beta-diol 2, 16beta
      hydroxymethyl-5alpha-androstane-3beta,17alpha-diol 3 and 16alpha-hydroxymethyl
      5alpha-androstane-3beta,17alpha-diol 4 with proven configuration were converted
      into the corresponding 16beta-methyl-5alpha-androstane-3beta,17beta-diol 5,
      16alpha-methyl-5alpha-androstane-3beta,17beta-diol 6, 16beta-methyl-5alpha
      androstane-3beta,17alpha-diol 7, 16alpha-methyl-5alpha-androstane-3beta,17alpha
      diol 8, furthermore into the 16beta-methyl-17beta-hydroxy-5alpha-androstane-3-one
      13, 16alpha-methyl-17beta-hydroxy-5alpha-androstan-3-one 14, 16beta-methyl
      17alpha-hydroxy-5alpha-androstan-3-one 15 and 16alpha-methyl-17alpha-hydroxy
      5alpha-androstan-3-one 16. The steric structures of the resulting epimers were
      determined by means of 1H-, and 13C-NMR spectroscopy. In this way, comparison was
      possible with the C-16 epimers 5, 6 and 13, 14 prepared earlier by a different
      route, and the series of isomers could be completed with the steric structures of
      16beta-methyl-17alpha-hydroxy-5alpha-androstan-3beta-ol 7 and 16alpha-methyl
      17alpha-hydroxy-5alpha 8 and with their 3-keto derivatives 15 and 16. The
      relative binding affinities of the 16-methyl-5alpha-androstane-3beta,17-diols 5,
      6, 7, 8 and 17-hydroxy-16-methyl-5alpha-androstan-3-ones 13, 14, 15, 16 were
      studied. The introduction of a 16-methyl substituent into 5alpha-androstane
      molecules substantially decreases the binding affinity to the androgen receptor
      and 16alpha-methyl derivatives were always bound more weakly than the 16beta
      methyl isomers.

PMID- 11576624
TI  - The 11beta hydroxysteroid dehydrogenase 2 exists as an inactive dimer.
AB  - The 11beta-hydroxysteroid dehydrogenase types 1 and 2 enzymes (11beta-HSD1 and
      11beta-HSD2), modulate glucocorticoid occupation of the mineralocorticoid and
      glucocorticoid receptors by interconverting corticosterone and cortisol to the
      inactive metabolites 11-dehydrocorticosterone and cortisone within the target
      cells. The NAD(+)-dependent 11-HSD 2 in the kidney inactivates corticosterone and
      cortisol, allowing aldosterone, which is not metabolized, access to the receptor.
      Studies of the kinetics of 11-HSD 2 activity in the rat kidney have produced
      inconsistent results. Western blots done in the absence of the reducing agent
      beta-mercaptoethanol showed two bands with approximate MW of 40 and 80 kDa. When
      beta-mercaptoethanol was used, only the 40 kDa was detected, indicating that
      under non-denaturing conditions a significant proportion of the 11beta-HSD 2
      exists as a dimer. NAD(+)-dependent conversion of 3H-corticosterone by 20 microg
      of microsomal protein increased approximately 10 fold with the addition of 5 mM
      DTT concentration. NADP(+)-dependent activity with 20 microg of microsomal
      protein was very low and did not change significantly when using DTT. In the
      presence of DTT, the predominant 11-HSD activity in the rat kidney is NAD(+)
      dependent with a K(m) of 15.1 nM, similar to that of the cloned and expressed
      enzyme. These data suggest that dimerization and subsequent enzyme inactivation
      occur when protocols promoting oxidation of this protein are used.

PMID- 11576625
TI  - The first product of phospholipid N-methylation,
      phosphatidylmonomethylethanolamine, is a lipid mediator for progesterone action
      at the amphibian oocyte plasma membrane.
AB  - Progesterone has been shown to act at plasma membrane receptors on the amphibian
      oocyte to trigger a cascade of changes in membrane phospholipids and to initiate
      the G(2)/M transition of the first meiotic division. The earliest event (0-1 min)
      is the transient N-methylation of phosphatidylethanolamine (PE) to form
      phosphatidylmonomethylethanolamine (PME), demonstrated using [(3)H]glycerol to
      prelabel oocyte plasma membrane PE. [(3)H]Glycerol-labeled PME rises 10-fold
      within the 1-2 min after exposure to progesterone and accounts for conversion of
      about 50% of the [3H]Glycerol-labeled PE. [(3)H]PME levels slowly decline over
      the following 10-30 min. [(3)H] or [(14)C] labeled fatty acid experiments showed
      that newly formed PME is enriched in linoleic or palmitic, but not in arachidonic
      acid, indicating that specific PE pools undergo progesterone-induced N
      methylation. Two plasma membrane changes: activation of serine protease, and
      Ca(2+) release from the oocyte surface coincide with PME formation; both are
      prevented by pretreatment of oocytes with the N-methylation inhibitor, 2
      methylaminoethane. Media containing PME micelles release both protease and Ca(2+)
      from intact oocytes within the first 1-2 min. The immediate downstream
      metabolites of PME, PDE and PC, do not induce serine protease activity or Ca(2+)
      release. We conclude that progesterone initially activates N-methyltransferase in
      the oocyte plasma membrane, and that the first product, PME, is responsible for
      activation of serine protease in the plasma membrane and the release of Ca(2+)
      from the oocyte surface.

PMID- 11576626
TI  - Histopathology and molecular genetics of hearing loss in the human.
AB  - Hearing loss is among the most common disabilities of man. It has been estimated
      that over 70 million individuals in the world are hearing impaired with pure tone
      averages greater than 55 dB. A genetic etiology is thought to be responsible for
      over half of early onset hearing loss and at least one third of late onset
      hearing loss. In this review, examples of the histopathology of the inner ear in
      known genetic syndromes in the human will be presented in order to provide a
      structural basis for understanding molecular mechanisms of development and
      maintenance in the inner ear, and to serve the essential function of validating
      the applicability of animal genetic models of hearing loss to the human
      condition.

PMID- 11576627
TI  - Prognostic factors of sudden hearing loss in children.
AB  - OBJECTIVE: Sudden hearing loss in children under 15 years old is rare and its
      pathophysiology remains unclear. The aim of this retrospective study was to
      define prognostic factors of sudden hearing loss in children under 15 years old.
      METHODS: Among the patients referred to our institution during the period 1990
      1999 for sudden hearing loss, 12 children were considered eligible for this study
      (mean age=9.5 years old). Patients were divided into three groups according to
      hearing recovery and seven putative prognostic factors were analyzed. RESULTS:
      Total hearing recovery (group I: 90-100%) occurred in 28.5% of cases, partial
      hearing recovery (group II: 11-89%) occurred in 28.5% of cases and absence of
      recovery (group III: 0-10%) was reported in 43% of cases. Factors such as age,
      sex, and bilaterality of hearing loss were not correlated with hearing recovery.
      CONCLUSIONS: Initial severe hearing loss, associated vertigo and 'downward'
      audiometric curve were three negative prognostic factors of hearing recovery.
      Tinnitus has only been reported in children with partial or total hearing
      recovery.

PMID- 11576629
TI  - Histological insight into the pathogenesis of severe laryngomalacia.
AB  - OBJECTIVE: To correlate clinical and histological findings in patients with
      laryngomalacia who required surgical intervention. METHODS: Retrospective study
      of all patients undergoing supraglottoplasty by a single surgeon (MEG) for severe
      laryngomalacia between October, 1999 and November, 2000. RESULTS: Nine patients
      were identified, of which seven had clinical evidence of GER. Seven patients had
      co-existing abnormalities or delays of neuromuscular development including
      seizure disorder, agenesis of the corpus callosum, obstructive sleep apnea,
      primary aspiration, a history of apparent life-threatening events, and
      craniosynostosis. Varying degrees of subepithelial edema and significant dilation
      of the subepithelial lymphatics were noted in all specimens. Submucosal
      inflammation was minimal to mild, and intraepithelial inflammation was rare to
      absent in all sections. No submucosal gland hyperplasia was seen in the samples
      from any patient. Two specimens contained cuneiform cartilage, both of which were
      histologically characterized as fibrocartilage. CONCLUSIONS: In this series, the
      histopathology of tissue excised during the treatment of severe laryngomalacia
      was dominated by submucosal edema and lymphatic dilation. Further study is needed
      to investigate comorbidities that may contribute to the need for intervention in
      children with laryngomalacia.

PMID- 11576628
TI  - Pattern changes of mucin gene expression with pneumococcal otitis media.
AB  - OBJECTIVE: mucins, known to be important components of the mucociliary transport
      system in the middle ear and Eustachian tube, are subject to changes under
      inflammatory conditions. Which mucin genes are up-regulated or activated during
      an inflammatory reaction of the middle ear and Eustachian tube, however, is
      poorly understood. The purpose of this study was to characterize mucin gene
      expression in middle ears and Eustachian tubes with pneumococcal ear infection.
      METHODS: sixteen rats received intrabullar inoculation of Streptococcus
      pneumoniae type 6A at 2.5x10(6) colony forming units (CFU). Four animals were
      sacrificed on days 1, 3, 7, and 14, respectively. The profile of mucin gene
      expression in the middle ear and Eustachian tube was examined by reverse
      transcription polymerase chain reaction (RT-PCR) at the above time points.
      Sixteen rats that received intrabullar inoculation of phosphate-buffered saline
      (PBS) served as controls. RESULTS: the Muc2 mucin gene was expressed in middle
      ear mucosa of the control rats. Following pneumococcal inoculation, Muc1-Muc5
      mucin genes were expressed in the middle ear mucosa in a time-dependent manner.
      In the Eustachian tube, the Muc2, Muc4 and Muc5 mucin genes were expressed in
      both control and pneumococcal inoculation groups. CONCLUSION: Muc1, Muc3, Muc4,
      and Muc5 mucin genes were activated in the middle ear mucosa by pneumococci,
      which may contribute to hyper-production of mucin in acute pneumococcal otitis
      media.

PMID- 11576630
TI  - Screening for auditory neuropathy in a school for hearing impaired children.
AB  - OBJECTIVE: Hearing loss in children may be due to a wide variety of pathologies.
      Recently, use of otoacoustic emission technology has led to identification of
      auditory neuropathy as a distinct hearing disorder. Children with auditory
      neuropathy require audiological and educational management that may differ from
      that required by other hearing impaired students. For this reason, screening for
      auditory neuropathy may be appropriate for children attending schools for the
      hearing impaired. The study investigated the utility of using otoacoustic
      emission measures for school screening of hearing impaired children. METHODS: In
      this study, 81 children aged 6-12 years who attended one school for the deaf were
      screened for indications of auditory neuropathy. Children found to have
      consistent otoacoustic emissions were given a full diagnostic audiological test
      battery. RESULTS: Two children had transient otoacoustic emission results
      indicating normal outer hair cell function in one or both ears. A follow-up
      diagnostic assessment for the two positive cases was strongly suggestive of
      auditory neuropathy. CONCLUSIONS: There is a need for routine auditory neuropathy
      screening at schools for hearing impaired children.

PMID- 11576631
TI  - Restricted use of antibiotic prophylaxis for recurrent acute otitis media in the
      era of penicillin non-susceptible Streptococcus pneumoniae.
AB  - OBJECTIVE/INTERVENTION: To compare the annual rates of acute otitis media (AOM)
      episodes, antibiotic days, and ventilating tube insertion during the first 3
      years of life before and after a practice change to restrict use of antibiotic
      chemoprophylaxis for recurrent AOM. METHODS SETTING: The sole pediatric private
      practice in a rural Kentucky community. PATIENTS: Population-based sample of all
      children born consecutively in two different 13 month intervals. Cohort 1 (n=251)
      was born before and Cohort 2 (n=274) was born after restricted use of
      chemoprophylaxis and documented emergence of widespread penicillin non
      susceptible Streptococcus pneumoniae (PNSP). DESIGN: Retrospective case cohort
      comparison. MAIN OUTCOME MEASURES: Suppurative AOM diagnosed by validated
      experienced otoscopists using stringent tympanic membrane criteria. RESULTS:
      Children were mostly white with the majority (50-65%) enrolled in daycare during
      each year. The first episode of AOM was experienced by 6 and 12 months of age in
      64 and 86%, respectively. Rates of children with recurrent AOM in Cohorts 1 and 2
      were 28 and 31% in Year 1, 17 and 23% in Year 2, and 7 and 10% in Year 3,
      respectively. Rates of new onset AOM and persistent AOM episodes were similar
      between cohorts in the first 2 years. Number of days of antibiotic prophylaxis
      were reduced from 11.2 to 3.4 days in Year 1, from 11.9 to 2.6 days in Year 2,
      and from 6.9 to 0.7 days in Year 3, respectively (P<0.0001 for each year). Total
      antibiotic days for Years 1, 2 and 3 were reduced commensurately with
      prophylactic days from 61.7 to 55.5 days (nonsignificant), from 56.3 to 45.8 days
      (P=0.047), and from 38.7 to 25.7 days (P<0.0001), respectively. For each year a
      non-significant trend for increased ventilating tube placement from Cohort 1 to
      Cohort 2, respectively, was observed, 2 versus 2.2%, 4 versus 5.8%, and 0.8
      versus 2.6%. Daycare attendance and white race were consistently significant risk
      factors for AOM and recurrent AOM. CONCLUSIONS: In the era of PNSP, restricted
      use of antibiotic chemoprophylaxis for recurrent AOM was not associated with
      significantly increased rates of new onset AOM episodes or tube placement in the
      first 24 months of life. Total antibiotic days were also significantly reduced in
      Cohort 2 during Years 2 and 3.

PMID- 11576632
TI  - Negative pressure tympanograms in children less than 2 years of age--different
      bacterial findings in otitis media by tympanometric results.
AB  - OBJECTIVE: The interpretation of negative pressure tympanograms as indicators of
      the presence of middle ear fluid has been ambiguous. Our purpose was to assess
      the occurrence and implications of negative pressure tympanograms and to study
      their association with bacterial pathogens in otitis media. METHODS: Altogether
      329 infants were enrolled at a well-baby clinic for the Finnish Otitis Media
      Cohort Study, a longitudinal prospective cohort study. The children were closely
      followed in a special study clinic from 2 to 24 months of age for respiratory
      diseases, especially acute otitis media. Children were examined at the study
      clinic with tympanometry and pneumatic otoscopy whenever visiting the study
      clinic for respiratory disease. Myringotomy with aspiration was performed if
      middle ear fluid was suspected in otoscopy. Occurrence of middle ear fluid in
      ears with negative pressure tympanograms (less than -100 daPa) was assessed.
      Nested case control design matched by visit type (acute or follow-up visit) and
      month of visit was used for analysis of association of bacterial pathogens and
      tympanometric results. RESULTS: Middle ear fluid was encountered in 15% of ears
      with negative tympanometric peak pressure, a lower proportion than described
      previously. In otitis media with a negative tympanometric peak pressure, 71% of
      bacterial cultures remained negative for the main pathogens, compared to 36% in
      matched controls (P<0.001). Especially Streptococcus pneumoniae but also
      Haemophilus influenzae were rarely found in samples from negative pressure ears.
      Moraxella catarrhalis was equally often found. CONCLUSIONS: Negative pressure
      tympanogram is a poor indicator for the presence of middle ear fluid.
      Furthermore, if otitis media is diagnosed with negative tympanometric peak
      pressure negative middle ear bacterial culture for the main pathogens is highly
      probable. Expectant follow-up might be more appropriate than routine antibiotic
      treatment.

PMID- 11576633
TI  - Assessment of congenital bony nasal obstruction by 3-dimensional CT volume
      rendering.
AB  - The nature and extent of congenital bony nasal obstruction is best determined by
      X-ray computed tomography (CT) imaging. Three-dimensional volume rendering of CT
      images provides an integrated perspective that can assist in clinical decision
      making and in operative planning. Clinical cases of choanal atresia and pyriform
      aperture stenosis are reviewed with their images. The authors propose this
      modality as an evolving standard for imaging of congenital bony nasal
      obstruction.

PMID- 11576634
TI  - Fetal rhabdomyoma of the posterior cervical triangle.
AB  - Rhabdomyoma is an uncommon benign tumor, with the majority arising from cardiac
      muscle. Seventy to 90% of extracardiac rhabdomyomas are found in the head and
      neck region, usually within the upper aerodigestive tract. The case of a 7-month
      old boy with an enlarging posterior triangle neck mass found to be fetal
      rhabdomyoma is presented. This location is quite rare for benign rhabdomyoma,
      with previous literature search showing overwhelming predilection for the upper
      aerodigestive tract.

PMID- 11576635
TI  - Laryngo-pharyngeal carcinoma in childhood.
AB  - Laryngo-pharyngeal carcinoma is rare in children. We present two cases of
      squamous cell carcinoma of the laryngopharynx in children less than 15 years of
      age. Both patients presented with a prolonged history of symptoms and extensive
      disease at diagnosis. Early visualisation the vocal cords with flexible
      larygnoscopy is important in children presenting with symptoms suggestive of
      laryngeal pathology. Long-term complications of definitive local therapy for
      laryngopharyngeal carcinoma are important in young children. Evidence from
      studies in adult patients suggests that adjuvant chemotherapy may play a role in
      laryngeal preservation in a select group of patients.

PMID- 11576636
TI  - Sequence and phylogenetic analysis of the sigmaA-encoding gene of avian reovirus.
AB  - The full-length sigmaA-encoding gene nucleotide sequences (1251 bp) of ten avian
      reovirus (ARV) field-isolates and three vaccine strains were determined and
      analyzed to study the degree of genetic divergence and evolution. Strains were
      isolated over a 23-year period from different hosts, pathotypes, and geographic
      locations. A phylogenetic tree constructed from variation in the sigmaA
      nucleotide sequences among ARV isolates showed that Taiwanese isolates from
      different dates of isolation were grouped into two distant groups, indicating
      that they have evolved in nature. In paired identity analysis, there was over
      97.3% nucleotide sequence identity in the sigmaA-encoding genes between group I
      Taiwanese isolates (T6, 750505, 919, and 918) and Japanese isolate OS161 as well
      as three US vaccine strains, suggesting that they might have descended from a
      common ancestor. However, the nucleotide sequences of these sigmaA-encoding genes
      varied extensively from those of group II Taiwanese isolates (601SI, R2/TW, 1017
      1, 916, and 601G), displaying only 86% identity. These results revealed that the
      genetic diversity in the sigmaA-encoding gene of ARV correlated with the date of
      isolation and geographic locations.

PMID- 11576637
TI  - A comparison of techniques for detecting Invertebrate iridescent virus 6.
AB  - The aim of this study was to compare the sensitivity and precision of various
      methods for the detection and quantification of Invertebrate iridescent virus 6
      (IIV-6) (Iridoviridae) isolated from a the stem-boring moth Chilo suppressalis,
      and to apply these techniques to the detection of covert infections in the wax
      moth, Galleria mellonella. The relationship between the virus concentration and
      absorbance at 260 nm was linear over the range of 1.6 x 10(9)-5.6 x 10(10)
      particles/ml. TCID(50) assays using 12 different cell lines indicated that two
      Drosophila lines, DL2 and DR1, had the highest susceptibility whereas cell lines
      from Aedes albopictus and Plutella xylostella were four orders of magnitude less
      sensitive. TCID(50) values for IIV-6 in Spodoptera frugiperda Sf9 cells gave the
      particle-infectivity ratios of 15-64 virus particles/IU. An insect bioassay
      involved injecting doses of 1-100 IIV-6 particles into the third instar G.
      mellonella larvae. The prevalence of patent infection was 20-26% at a dose of 1
      particle per larva rising to 86-92% at 10 particles and 100% at doses of 50 or
      100 particles. Of the insects that survived to adulthood, between 5.8 and 75%
      caused patent infections when injected into G. mellonella larvae, indicating that
      they were covertly infected. A PCR technique resulted in 95% detection at 1000
      virus particles per insect. Of the insects that proved positive for covert
      infection by insect bioassay, 41% also proved positive by PCR analysis. It is
      concluded that the G. mellonella bioassay is highly reliable for detection of
      doses of 10 particles or more and for determining the relative activity of IIV-6
      preparations at doses as low as 1 particle per insect. PCR had a slightly lower
      sensitivity followed by the insect cell culture assay.

PMID- 11576638
TI  - Comparison of techniques for extracting viral RNA from isolation-negative serum
      for dengue diagnosis by the polymerase chain reaction.
AB  - Aiming at the improvement of the molecular diagnosis of dengue, three well
      established methods of RNA extraction from serum of patients with clinical
      symptoms of dengue were compared. The methods were based on the QIAamp Viral RNA
      kit, the Chomczynski-Sacchi technique and TRIzol. One hundred samples were
      examined using the same protocol for reverse transcription-polymerase chain
      reaction (RT-PCR). Out of the 100 samples tested, none was positive by either the
      Chomczynski-Sacchi technique or TRIzol, and six were positive using the QIAamp
      viral RNA kit. Of the six positive samples, only one was collected before 5 days
      of the beginning of the disease, and it was also positive for viral isolation.
      These results were confirmed later by serology (MAC-ELISA) that showed that 19
      samples were positive for IgM antibodies against dengue. These data indicate that
      PCR is a useful method for detection of dengue virus infections in IgM-positive
      samples, and the best method of RNA extraction from clinical samples, to be used
      for dengue diagnosis by PCR is the QIAamp Viral RNA kit.

PMID- 11576639
TI  - Optimization of cottontail rabbit papilloma virus challenge technique.
AB  - Disease induced by Cottontail Rabbit Papilloma Virus (CRPV) scarification in
      domestic rabbits shares many attributes with disease induced by human papilloma
      virus (HPV). CRPV induces squamous papillomas in domestic rabbits, of which
      approximately 70% transform into invasive carcinomas. In advanced tumors, virus
      is often undetectable, and occasionally, some rabbits undergo spontaneous
      regression of papillomas. Techniques utilized to scarify rabbit skin are diverse,
      often labor intensive and time consuming with the possibility for significant
      variability. Using four unique infection techniques, resultant papilloma
      incidence, time to onset, and total papilloma volumes were compared to determine
      an optimal challenge method. Five rabbits were each infected with CRPV via a
      tattoo gun with and without ink, an intradermal injection, manual use of a tattoo
      needle, or a sterile blade followed by manual use of a tattoo needle. Papilloma
      formation was monitored weekly after inoculation for 6 weeks. CRPV papillomas
      began as pinpoint foci at 3 weeks post challenge and grew exponentially
      throughout the course of measurement. Individual foci coalesced rapidly to form
      larger papilloma aggregates. Although intradermal injection was well tolerated
      and easily performed, it was the worst method of papilloma production (2.2 mm(3)
      at 6 weeks). The best method, a sterile blade followed by manual use of a tattoo
      needle, produced significantly larger papillomas over all time periods (>1100
      mm(3) at 6 weeks, P<0.01). Inoculation of CRPV using this method produces highly
      repeatable papillomas beginning 3 weeks post-infection.

PMID- 11576640
TI  - Transmission of viral RNA and DNA to maize kernels by vascular puncture
      inoculation.
AB  - Vascular puncture inoculation (VPI) is an effective technique for transmission of
      maize viruses without using arthropods or other biological vectors. It involves
      using a jeweler's engraving tool to push minuten pins through a droplet of virus
      inoculum toward the major vascular bundle in the scutellum of germinating
      kernels. Here, VPI is shown to be useful for introducing RNA and DNA viral
      genomes into maize. Maize dwarf mosaic potyvirus (MDMV) virions, MDMV genomic
      RNA, foxtail mosaic potexvirus (FoMV) genomic RNA and maize streak geminivirus
      (MSV) DNA were introduced into kernels by VPI, and infection rates determined. At
      high concentrations, both MDMV virion and genomic RNA preparations produced 100%
      infection of susceptible maize. However, MDMV genomic RNA was transmitted with
      about 100-fold lower efficiency than virions. FoMV genomic RNA and MSV DNA were
      transmitted at lower efficiency than the MDMV RNA, and the highest transmission
      rates were about 50%. Ribonuclease A pretreatment prevented genomic MDMV and FoMV
      RNA transmission, but not MDMV virion transmission indicating the viral RNA was
      the infectious entity. Proteinase K (ProK) pretreatment reduced transmission of
      MDMV RNA suggesting that integrity of the viral genomic protein bound covalently
      to the viral RNA may be important for efficient transmission.

PMID- 11576641
TI  - A human immunodeficiency virus Env inducible transcription system to examine
      consequences of gp120 expression.
AB  - According to several studies, the HIV-1 envelope gp120 protein and the co
      receptor CXCR4 play an essential role in HIV-1 induced cell toxicity.
      Characterisation of the CD4-independent m7NDK isolate provided the opportunity of
      studying the effects of direct interactions between m7NDK gp120 and CXCR4.
      Therefore, an inducible expression system was designed enabling synthesis of HIV
      1 Env proteins upon doxycycline induction. Analysis of the expression of the env
      gene of the m7NDK HIV-1 isolate revealed, unexpectedly, that even long-term
      expression of m7NDK gp120 did not result in cytotoxycity in CXCR4-positive or 
      negative cell lines. This is the first report of a CD4-independent HIV-1-protein
      inducible expression regulated through the Tet-On system and by an alternative
      splicing. Env inducible expression cell lines could constitute a useful cellular
      tool to undertake analysis of HIV Env protein expression.

PMID- 11576642
TI  - Determination of hepatitis B virus genotype G by polymerase chain reaction with
      hemi-nested primers.
AB  - Hepatitis B virus (HBV) has been classified into six genotypes designated A-F by
      sequence divergence in the entire genome exceeding 8%. Very recently, the seventh
      genotype was reported and named genotype G. HBV genotype G is distinct from
      genomes of the other six genotypes in that it possesses an insertion of 36
      nucleotides in the core gene, and has been found so far in France and the United
      States. A method for determining HBV genotype G was developed by polymerase chain
      reaction (PCR) with primers deduced from the 36-nucleotide (nt) insertion in five
      isolates of HBV genotype G the sequences of which have been deposited in DNA
      databases. The validity of this method, for specifically detecting HBV genotype
      G, was verified on a panel consisting of 142 HBV isolates of six major genotypes
      and four of genotype G. A total of 540 sera containing HBV in Japan covering
      symptom free carriers and patients with a spectrum of chronic liver disease were
      tested by this method, but not a single HBV genotype G sample was found. A
      possible method for serological determination of hepatitis B surface antigen of
      genotype G is suggested, without amplification or sequencing nucleotides, which
      would expand epidemiological and clinical researches on HBV genotype G.

PMID- 11576643
TI  - The replication of certain Coxsackie B virus strains in CHO cells.
AB  - Cell surface molecules that can act as viral receptors may exert an important
      selective pressure on RNA viral quasi-species. Coxsackie-Adenovirus Receptor and
      Decay Accelerating Factor (DAF, CD55) have been identified as receptors for
      Coxsackie B virus. In studies of viral replication using different strains of
      Coxsackievirus serotype 4 (CBV-4), it was found that despite lack of expression
      of these cell surface molecules on Chinese Hamster Ovary (CHO) cells and despite
      their common use as negative controls in Coxsackie B virus receptor assays, two
      strains were able to replicate, one (V89-4557) without cytopathic effect (CPE),
      and the other (T318) with strong CPE. A weak signal was obtained using antibodies
      against enterovirus, visualized with FITC-conjugated antibodies, when the
      Coxsackievirus B4 strain V89-4557 was inoculated on CHO cells compared to no
      signal with the non-replicating Coxsackievirus B4 strain VD2921, indicating some
      degree of binding of the former to the cells.

PMID- 11576644
TI  - Increasing the efficiency of virus infectivity assays: small inoculum volumes are
      as effective as centrifugal enhancement.
AB  - Improving the virus particle:infectious unit ratio is a continuing goal for
      animal virologists. It is demonstrated for an influenza A virus that decreasing
      the size of the inoculum volume to 10 microl per well of a 96-well plate was as
      effective as using centrifugal force with inoculum up to 250 microl. Both
      achieved a 7.5-fold increase in infectivity in monolayers of MDCK cells compared
      with standard conditions. The underlying principle of both methods is to bring
      virus particles into close contact with cell receptors.

PMID- 11576646
TI  - That's your left foot and...
AB  - Olfaction involves pattern recognition processes: in the olfactory bulb each odor
      is represented as a specific spatial activity pattern, serving as the basis for
      downstream spatiotemporal encoding and odor perception. The principle of pattern
      generation, the general properties of the patterns and new evidence regarding the
      functions of the patterns are discussed.

PMID- 11576647
TI  - Peripheral metabotropic glutamate receptors: fight the pain where it hurts.
AB  - Recent anatomical and behavioral data show the expression of G-protein coupled
      metabotropic glutamate receptors in the periphery on nociceptive primary afferent
      nerve terminals, and provide evidence for a functional role of peripheral
      metabotropic glutamate receptors in inflammatory pain. These findings have
      important implications for new therapeutic strategies that target peripheral
      metabotropic glutamate receptors for pain relief. They also alert us to the
      necessity of assessing drug effects at different levels of the nervous system:
      peripheral and central.

PMID- 11576648
TI  - Plasticity: downstream of glutamate.
AB  - Glutamate neurotransmission is an essential component of many forms of neuronal
      plasticity, however, the intracellular mechanisms that mediate plasticity are
      only beginning to be elucidated. The emerging image of the NMDA receptor complex
      reminds us that the similarity between mechanisms of plasticity in various model
      systems is greater than their apparent differences. For example, the cAMP
      dependent protein kinase A signalling pathway is crucial for plasticity in a
      variety of neuronal systems and across a wide variety of species.

PMID- 11576649
TI  - Dual use of the transcriptional repressor (CtBP2)/ribbon synapse (RIBEYE) gene:
      how prevalent are multifunctional genes?
AB  - Vertebrates have ribbon synapses in the retina and in other sensory structures
      that are specialized for rapid, tonic release of synaptic vesicles (1). The
      lamellar sheets of the ribbon situated at right angles to the plasma membrane are
      lined with synaptic vesicles that undergo exocytosis under the influence of
      Ca(2+). Synaptic ribbons act as a conveyer belt to accelerate the release of this
      ready supply of synaptic vesicles at the presynaptic membranes. Although the
      protein composition of the terminals of ribbon synapses is generally similar to
      that of ordinary synapses in nervous tissue, much less is known about the
      composition of the ribbons themselves. RIM, a universal component of presynaptic
      active zones that interacts with rab3 on the synaptic vesicle, has been localized
      to the ribbons (2). In addition, the kinesin motor protein, KIF3A, is associated
      with the ribbons and other organelles in presynaptic nerve terminals (3).
      Recently, an approximately 120 kDa protein called RIBEYE has been identified in
      purified ribbons of bovine retina. The RIBEYE cDNA was cloned and its gene
      identified in the database.

PMID- 11576650
TI  - Susceptibility gene(s) for Alzheimer's disease on chromosome 10.
AB  - The majority of Alzheimer's disease is inherited in a complex manner involving
      environmental factors and several genes. One of these genes is Apolipoprotein E
      where the polymorphic allele (APOE epsilon 4) has been robustly shown to modify
      risk and the course of Alzheimer's disease. The epsilon 4 allele however, only
      accounts for approximately 50% of late onset Alzheimer's disease. Here we review
      three quite different approaches that have led to convincing evidence that there
      is at least one other susceptibility gene for complex inherited forms of
      Alzheimer's disease on chromosome 10q. Two linkage studies give strong evidence
      of a locus at almost exactly the same location: one using the amyloid beta brain
      deposited fragment of the amyloid precursor protein as a continuous phenotype,
      and the other using a categorical disease phenotype. A third candidate gene
      linkage and association analysis approach interestingly finds a maximum signal
      approximately 35-60cM distal to the previous studies.

PMID- 11576651
TI  - LTP gets culture.
AB  - In a recent breakthrough, a methodology has been developed for studying
      persistent enhancement of excitatory synaptic transmission in primary cultures of
      hippocampus. Results from the use of this method have already pointed to a
      previously unsuspected differential role for synaptic versus extrasynaptic NMDA
      receptors in lasting synaptic potentiation.

PMID- 11576652
TI  - A database generator for human brain imaging.
AB  - Sharing scientific data containing complex information requires new concepts and
      new technology. NEUROGENERATOR is a database generator for the neuroimaging
      community. A database generator is a database that generates new databases. The
      scientists submit raw PET and fMRI data to NEUROGENERATOR, which then processes
      the data in a uniform way to create databases of homogeneous data suitable for
      data sharing, met-analysis and modelling the human brain at the systems level.
      These databases are then distributed to the scientists.

PMID- 11576656
TI  - Untangling the enigmatic tau.

PMID- 11576669
TI  - Vitamin D: the neglected neurosteroid?

PMID- 11576670
TI  - Do active cerebral neurons really use lactate rather than glucose?
AB  - Glucose has long been considered the substrate for neuronal energy metabolism in
      the brain. Recently, an alternative explanation of energy metabolism in the
      active brain, the astrocyte-neuron lactate shuttle hypothesis, has received
      attention. It suggests that during neural activity energy needs in glia are met
      by anaerobic glycolysis, whereas neuronal metabolism is fueled by lactate
      released from glia. In this article, we critically examine the evidence
      supporting this hypothesis and explain, from the perspective of enzyme kinetics
      and substrate availability, why neurons probably use ambient glucose, and not
      glial-derived lactate, as the major substrate during activity.

PMID- 11576671
TI  - The neurobiology of learning and memory: some reminders to remember.
AB  - We have learned much about the neurobiology of learning and memory in the past
      100 years. We have also learned much about how we should, and should not,
      investigate these complex processes. However, with the rapid recent growth in the
      field and the influx of investigators not familiar with this past, these crucial
      lessons too often fail to guide the research of today. Here we highlight some
      major lessons gleaned from this wealth of experience. These include the need to
      carefully attend to the learning/performance distinction, to rely equally on
      synthetic as well as reductionistic thinking, and to avoid the seduction of
      simplicity. Examples in which the lessons of history are, and are not, educating
      current research are also given.

PMID- 11576672
TI  - Ischemic injury and faulty gene transcripts in the brain.
AB  - The brain has the highest metabolic rate of all organs and depends predominantly
      on oxidative metabolism as a source of energy. Oxidative metabolism generates
      reactive oxygen species, which can damage all cellular components, including
      protein, lipids and nucleic acids. The processes of DNA repair normally remove
      spontaneous gene damage with few errors. However, cerebral ischemia followed by
      reperfusion leads to elevated oxidative stress and damage to genes in brain
      tissue despite a functional mechanism of DNA repair. These critical events occur
      at the same time as the expression of immediate early genes, the products of
      which trans-activate late effector genes that are important for sustaining
      neuronal viability. These findings open the possibility of applying genetic tools
      to identify molecular mechanisms of gene repair and to derive new therapies for
      stroke and brain injury.

PMID- 11576673
TI  - Neural activity: sculptor of 'barrels' in the neocortex.
AB  - A major portion of the primary somatosensory cortex of rodents is characterized
      by the discrete and patterned distribution of thalamocortical axons and layer IV
      granule cells ('barrels'), which correspond to the spatial distribution of
      whiskers and sinus hairs on the snout. In recent years several mutant mouse
      models began unveiling the cellular and molecular mechanisms by which these
      patterns emerge presynaptically and are reflected postsynaptically. Neural
      activity plays a crucial role in conferring presynaptic patterns to postsynaptic
      cells via neurotransmitter receptor-mediated intracellular signals. Here we
      review recent evidence that is finally opening the doors to understanding the
      cellular and molecular mechanisms of pattern formation in the neocortex.

PMID- 11576674
TI  - The thalamic matrix and thalamocortical synchrony.
AB  - High-frequency synchronous activity of neurons in the cerebral cortex and
      thalamus is a concomitant of discrete conscious events. In the primate thalamus,
      a newly identified population of neurons provides a basis for this
      synchronization. A matrix of calbindin-immunoreactive neurons extends throughout
      the thalamus and projects to superficial layers of cortex over wide areas,
      unconstrained by boundaries between areas. In some nuclei, a core of parvalbumin
      immunoreactive neurons is superimposed upon the matrix. Core neurons project in a
      topographically ordered fashion to middle layers of the cortex in an area
      specific manner. Matrix neurons, recruited by corticothalamic connections, can
      disperse activity across cortical areas and thalamic nuclei. Their superficial
      terminations can synchronize specific and nonspecific elements of the
      thalamocortical network in coherent activity that underlies cognitive events.

PMID- 11576675
TI  - Structural complexity and functional diversity of endoplasmic reticulum Ca(2+)
      stores.
AB  - Considerable evidence, including recent direct observations, suggest that
      endoplasmic reticulum (ER) Ca(2+) stores in neurons, glia, and other cell types,
      consists of spatially-distinct compartments that can be individually loaded and
      unloaded. In addition, sub-plasmalemmal ('junctional') components of the ER (jER)
      are functionally coupled to the overlying plasmalemmal (PL) microdomains in PL
      jER units named 'PLasmERosomes'. The PL microdomains and the jER contain clusters
      of specific transport proteins that regulate Na(+) and Ca(2+) concentrations in
      the tiny cytosolic space between the PL and jER. This organization helps the ER
      to produce the many types of complex local and global Ca(2+) signals that are
      responsible for the simultaneous control of numerous neuronal and glial
      functions.

PMID- 11576676
TI  - Self-referent phenotype matching: theoretical considerations and empirical
      evidence.
AB  - In most birds and mammals, young are raised in family groups. The phenotypes of
      nestmates and parents are thus reliable cues for recognition of conspecifics and
      kin. However, in some species, young develop alone, or in broods of mixed
      relatedness (e.g. because of multiple paternity or maternity), or among
      heterospecifics or unrelated conspecifics (brood parasites). Under these
      circumstances, the best referent (model) for discriminating close from distant
      kin and heterospecifics from conspecifics might be one's own self. This
      recognition process is known as self-referent phenotype matching. Here we review
      recent experimental evidence of self-referencing and suggest that behavioral
      neuroscience can provide new tools and insights into how it works (its proximate
      mechanistic and ontogenetic bases) and why it exists (its adaptive significance).

PMID- 11576677
TI  - Environment complexity stimulates visual cortex neurogenesis: death of a dogma
      and a research career.
AB  - Over the past few years, the classic idea that no new nerve cells are born in the
      adult mammalian brain has finally and conclusively been refuted by the scientific
      community. Yet, the first indications that neurogenesis occurs in the brain of
      adult mammals were obtained using light and electron microscopy over two decades
      ago. Why this went unrecognized is described in a personal account by the
      researcher who pioneered those studies: Michael Kaplan.

PMID- 11576678
TI  - Novel vaccine strategies to T-independent antigens.
AB  - T cell independent antigens do not require T cell help to induce an immune
      response, and are characterized by a lack of immunologic memory. These antigens
      can be divided into two classes, TI-1 or TI-2. TI-1 antigens, such as bacterial
      lipopolysaccharide, are potent B-cell mitogens, capable of non-specific,
      polyclonal activation of B cells. In contrast, TI-2 antigens can only activate
      mature B cells and consist of highly repetitive structures, such as capsular
      polysaccharides (CPS) from bacteria. Many vaccines currently in use consist of
      purified capsular polysaccharides from pathogenic bacteria such as Streptococcus
      pneumoniae and Neisseria meningitidis. These vaccines are efficacious in immune
      competent adults, however, due to their TI-2 nature, are not effective in
      children <2 years of age. Converting polysaccharides into T cell dependent (TD)
      antigens, allows children, <2, to produce an effective immune response. This
      review focuses on various strategies used to convert the immune response to
      polysaccharide antigens from TI-2 to a TD response. Conjugate vaccines, anti
      idiotypic antibodies, phage display library technology and DNA vaccines are
      discussed.

PMID- 11576679
TI  - Animal models of infection and inflammation and their role in experimental
      nuclear medicine.
AB  - In this review, basic aspects of nuclear medicine are described. One of the
      fields of research in nuclear medicine is the development of new
      radiopharmaceuticals for imaging infection and inflammation in humans. For this
      development, animal models are identified and modified to needs of a particular
      research question. In this review, a wide variety of models that are available in
      our laboratory are presented and the strengths and pitfalls are discussed.

PMID- 11576680
TI  - A novel method for the measurement of dissolved adenosine and guanosine
      triphosphate in aquatic habitats: applications to marine microbial ecology.
AB  - A novel method for the measurement of dissolved adenosine-5'-triphosphate and
      guanosine-5'-triphosphate (D-ATP and D-GTP, respectively) in marine and
      freshwater habitats was developed and applied to samples collected from the
      oligotrophic North Pacific Ocean. Both D-ATP and D-GTP are co-precipitated by
      authigenically formed Mg(OH)(2) and can be concentrated by factors greater than
      200-fold, for subsequent measurement by the firefly luciferin-luciferase
      bioluminescence reaction. The detection limit for this method was 2-3 pmol ml(-1)
      of concentrated sample (equivalent to an in situ concentration of 10 pM) with a
      5% precision at concentrations of 10 pmol ml(-1) or above.A significant positive
      correlation (P<0.001) was observed between particulate ATP (P-ATP) and D-ATP in
      water samples collected from Station ALOHA (22.75 degrees N, 158 degrees W; depth
      profiles 0-1000 m). The highest concentrations of dissolved nucleotides were
      found in the euphotic zone (0-175 m) below which the concentrations were low and
      relatively invariant. The dissolved nucleotide pools generally exceeded their
      corresponding particulate pools.Using radioisotopic tracer techniques and the new
      concentration method, turnover times for both particulate and dissolved
      nucleotides can be determined. The ability to measure concentrations and follow
      nucleotide tracers accurately in a very dilute environment provides a unique
      opportunity to address questions on microbial community metabolism, nutrient
      dynamics and energy flux.

PMID- 11576681
TI  - Objective threshold selection procedure (OTS) for segmentation of scanning laser
      confocal microscope images.
AB  - The determination of volumes and interface areas from confocal laser scanning
      microscopy (CLSM) images requires the identification of component objects by
      segmentation. An automated method for the determination of segmentation
      thresholds for CLSM imaging of biofilms was developed. The procedure, named
      objective threshold selection (OTS), is a three-dimensional development of the
      approach introduced by the popular robust automatic threshold selection (RATS)
      method. OTS is based on the statistical properties of local gray-values and
      gradients in the image. By characterizing the dependence between a volumetric
      feature and the intensity threshold used for image segmentation, the former can
      be determined with an arbitrary confidence level, with no need for user
      intervention. The identification of an objective segmentation procedure renders
      the possibility for the full automation of volume and interfacial area
      measurement. Images from two distinct biofilm systems, acquired using different
      experimental techniques and instrumental setups were segmented by OTS to
      determine biofilm volume and interfacial area. The reliability of measurements
      for each case was analyzed to identify optimal procedure for image acquisition.
      The automated OTS method was shown to reproduce values obtained manually by an
      experienced operator.

PMID- 11576682
TI  - Colorimetric assay for Lindane dechlorination by bacteria.
AB  - A colorimetric microtitre plate-based assay that detects haloalkane dehalogenase
      activity was modified to detect dechlorination of gamma-hexachlorocyclohexane
      (Lindane). Dechlorination is indicated by the colour change of phenol red from
      red to yellow, in a weakly buffered solution, as the solution becomes acidic due
      to HCl formed during dechlorination. Enzyme activity can be monitored by reading
      the absorbance of each well at 540 nm. Positive controls for the assay were the
      known Lindane-degrading microorganisms, Rhodanobacter lindaniclasticus and
      Sphingomonas paucimobilis UT26. Dechlorination in a scaled-up version of the
      assay was confirmed by GC/ECD detection of known metabolites of the test
      microorganisms from which the enzyme extracts were prepared. The assay was used
      to measure the rate of dechlorination in cell-free extracts of R.
      lindaniclasticus. It was also used to screen the cell-free extracts of 24
      bacterial isolates, from a Lindane-contaminated soil, for Lindane dechlorination
      activity. Although no isolates tested positive, the assay represents a new
      inexpensive and rapid screening tool for the detection of Lindane-degrading
      microorganisms.

PMID- 11576683
TI  - Development of respirometry methods to assess the microbial activity of
      thermophilic bioleaching archaea.
AB  - Respirometry methods have been used for many years to assess the microbial
      activity of mainly heterotrophic bacteria. Using this technique, the consumption
      of oxygen and evolution of carbon dioxide for heterotrophic carbon catabolism can
      be used to assess microbial activity. In the case of autotrophic bioleaching
      bacteria, carbon dioxide is used as a carbon source resulting in the consumption
      of both oxygen and carbon dioxide. The use of such respirometry techniques at
      high temperatures (up to 80 degrees C) for the investigation of bioleaching
      Archaea, however, poses particular difficulties. At these elevated temperatures,
      the solubility of oxygen into the liquid phase is particularly poor. This work
      details specific methods by which high temperature constraints are overcome while
      monitoring the activity of thermophilic Archaea using a Micro-Oxymax respirometer
      (Columbus Instruments). The use of elevated headspace oxygen concentrations, in
      order to overcome low oxygen solubility, is demonstrated as well as the effect of
      such elevated oxygen concentrations on microbial oxygen consumption rates. The
      relative rates of oxygen and carbon dioxide consumption are also illustrated
      during the oxidation of a chalcopyrite concentrate. In addition, this paper
      details generic methods by which respirometry data can be used to quantify
      inhibitory effects of a compound such as Na(2)SO(4). The further use of such data
      in predicting minimum hydraulic reactor retention times for continuous culture
      bioleaching reactors, as a function of concentration of potentially inhibitory
      compounds, is also demonstrated.

PMID- 11576684
TI  - Bacterial inoculum enhances keratin degradation and biofilm formation in poultry
      compost.
AB  - Native microbial populations can degrade poultry waste, but the process can be
      hastened by using feather-degrading bacteria. Strains of Bacillus licheniformis
      and a Streptomyces sp. isolated from the plumage of wild birds were grown in a
      liquid basal medium and used to inoculate feathers in compost bioreaction
      vessels. Control vessels had only basal medium added to the feathers, litter and
      straw. Temperature, ammonia, carbon and nitrogen were monitored for 4 weeks.
      Scanning electron microscopy of the feather samples showed more complete keratin
      degradation, more structural damage, and earlier microbial biofilm formation on
      inoculated feathers than on uninoculated feathers. A diverse community of aerobic
      bacteria and fungi were cultured early, but declined rapidly. Thermophilic B.
      licheniformis and Streptomyces spp. were abundant throughout. Enteric gram
      negative bacteria, (e.g., Salmonella, E. coli) originally found on waste feathers
      were not recovered after day 4. Vessel temperatures reached 64-71 degrees C
      within 36 h and stabilized at 50 degrees C. When tumble-mixed at day 14, renewed
      activity peaked at 59 degrees C and quickly dropped as available carbon was used.
      Feathers soaked in an inoculum of B. licheniformis and Streptomyces degraded more
      quickly and more completely than feathers that were not presoaked. Inoculation of
      feather waste could improve composting of the large volume of feather waste
      generated every year by poultry farms and processing plants.

PMID- 11576685
TI  - Rapid duplex PCR assay for the detection of pathogenic Yersinia enterocolitica
      strains.
AB  - For the detection of pathogenic Yersinia enterocolitica strains, a duplex PCR has
      been developed based on differences observed between the fingerprint profiles of
      pathogenic and non-pathogenic strains. The profiles were obtained by using a
      primer derived from the Enterobacterial Repetitive Intergenic Consensus (ERIC)
      sequences. From the sequence of one pathogen-specific amplified fragment, a
      discriminative primer has been designed bridging the sequence of the highly
      conserved core region and 3' end of the ERIC element. In combination with three
      other primers, all located within the detected open reading frame that resembled
      the sequence of the bipA gene, this primer was applied in a duplex PCR assay to
      simultaneously detect Y. enterocolitica and to discriminate between pathogenic
      and non-pathogenic strains. The same primer combinations were used in an on line
      rapid cycling real-time PCR assay. The used SYBR Green I format allowed for the
      easy translation of the PCR conditions and confirmation of the resulting
      amplicons. The time of analysis was reduced to approximately 60 min.

PMID- 11576686
TI  - Comparison of methods for monitoring bacterial transport in the subsurface.
AB  - The purpose of this study was to compare in a laboratory experiment, a suite of
      methods developed to track viable bacteria during field transport experiments.
      The criteria for development and selection of these methods included: (1) the
      ability to track bacteria within the environment from which they were isolated;
      (2) the lack of any effect upon the viability or the transport characteristics of
      the strain; (3) low detection limits; (4) a quantification range that covered
      several orders of magnitude; and (5) an analytical cost and turnover time
      commensurate with the analysis of several thousands of samples in a few months.
      The approaches developed included: enumeration of bacteria labeled with a vital
      fluorescent stain (CFDA/SE) using microplate spectrofluorometry, flow cytometry,
      and ferrographic (immunomagnetic) capture; enumeration of highly (13)C-enriched
      bacteria using combustion-IRMS; and quantitative PCR. These methods were compared
      to direct microscopic enumeration and plate counts during a bacterial transport
      experiment performed in an intact sediment core and designed to simulate the
      field experiment. Four of the seven methods had equivalent recoveries for the
      breakthrough of a pulse of bacteria eluting from a 50-cm long sediment core, and
      all of the methods detected the arrival of cells in the effluent prior to the
      conservative tracer. Combustion IRMS and ferrographic enumeration had the lowest
      quantification limits (approximately 2 to 20 cells/ml), whereas microplate
      spectrofluorometry had the highest quantification limit (approximately 10(5)
      cells/ml). These methods have the potential for numerous applications beyond
      tracking bacteria injected into the subsurface.

PMID- 11576687
TI  - Convenient fluorescence-based methods to measure membrane potential and
      intracellular pH in the Archaeon Methanobacterium thermoautotrophicum.
AB  - New and improved methods to determine the membrane potential (Delta Psi) and the
      Delta pH in methanogenic archaea were developed and tested in Methanobacterium
      thermoautotrophicum strain Delta H. The Delta pH measurements took advantage of
      the pH-dependent fluorescence properties of coenzyme F(420), the major
      intracellular electron carrier in the organism. The protonophore p-nitrophenol
      did not show any interference with the F(420) fluorescence spectra and was
      therefore suitable to equalize internal and external pH. The method developed
      allowed the determination of the intracellular pH with an error of less than 0.05
      pH units.Membrane potentials could easily be assessed using the fluorescent probe
      bis-(1,3-dibutylbarbituric acid)trimethine oxonol (DiBAC(4)(3)) with an accuracy
      of approximately 10 mV. Both methods were tested with cell suspensions of M.
      thermoautrophicum incubated at medium pH values between 5.5 and 8. It was found
      that Delta Psi and Delta pH values remained constant under these conditions.
      Membrane potentials were about -160 mV and Delta pH was kept at 0.35 pH units
      (inside minus outside) resulting in a total proton motive force of about -180 mV
      (inside negative).

PMID- 11576688
TI  - Performance of Pseudomonas CFC-selective medium in the fish storage ecosystems.
AB  - Pseudomonas agar base supplemented with cephaloridine, fucidin, and cetrimide
      (CFC) was used to count Pseudomonas populations on fish. Both Enterobacteriaceae
      and Shewanella putrefaciens were able to grow on the CFC medium. Evaluation of
      the performance of CFC-selective for pseudomonads medium, on fish samples stored
      aerobically and under a modified atmosphere at 0, 10 and 20 degrees C was tested.
      The selectivity of the medium was affected by storage temperatures and the type
      of packaging of the fish samples. The selectivity of the medium diminished as the
      population increased and for samples stored at high temperature (20 degrees C) or
      under modified atmospheres. When designing adequate selectivity of a medium,
      interfering organisms should be taken into account, especially when the
      background flora tends to be more robust than the organisms to be counted or
      detected.

PMID- 11576689
TI  - Effects of preparation method, age, and plating technique of thin agar layer
      media on recovery of Escherichia coli O157:H7 injured by sodium chloride.
AB  - The thin agar layer (TAL) method was experimentally tested to determine its
      ability to recover Escherichia coli O157:H7 injured by sodium chloride (NaCl).
      Cells grown in Brain Heart Infusion broth with 0%, 5%, or 7.5% (w/v) NaCl were
      spread and spiral plated onto Tryptic Soy agar (TSA), MacConkey Sorbitol agar
      (MSA), and TSA/MSA TAL combinations. Generally, TSA recovered more injured cells
      than TAL (p < or =0.05), and TAL recovered more cells than MSA (p < or =0.05).
      Preparation mode (two vs. three layers) and age (0, 1, or 7 days) of TAL had
      negligible effect on resuscitation of injured cells (p > 0.05). TAL, which is
      conventionally used to recover heat, cold, and acid-injured foodborne pathogens,
      may be used to recover NaCl-injured E. coli O157:H7.

PMID- 11576692
TI  - The drug efflux-metabolism alliance: biochemical aspects.
AB  - The considerable overlap in the substrate selectivity and tissue localization of
      CYP3A and P-glycoprotein has led to the hypothesis that this transporter and
      enzyme pair act as a coordinated absorption barrier against xenobiotics. A
      historical perspective on the investigation of this interactive alliance is
      given, starting from the understanding of the role of intestinal metabolism in
      explaining cyclosporine clinical data. Several animal studies using mdr1a-/-
      knockout mice have demonstrated P-glycoprotein's importance in limiting drug
      absorption and decreasing bioavailability. Human clinical studies investigating
      the importance of intestinal CYP3A and P-glycoprotein through inhibition or
      induction of these proteins have provided further evidence of this interaction.
      Recent in vitro studies using CYP3A4-expressing Caco-2 cells are reported. These
      studies reveal that the role of P-glycoprotein in the intestine extends beyond
      simply limiting parent drug absorption but also includes increasing the access of
      drug to metabolism by CYP3A through repeated cycles of absorption and efflux.

PMID- 11576693
TI  - Intestinal drug efflux: formulation and food effects.
AB  - The intestine, primarily regarded as an absorptive organ, is also prepared for
      the elimination of certain organic acids, bases and neutral compounds depending
      on their affinity to intestinal carrier systems. Several of the transport systems
      known to mediate efflux in the major clearing organs--liver and kidney--are also
      expressed in the intestine. Examples of secretory transporters in the intestine
      are P-glycoprotein, members of the multidrug resistance associated protein
      family, breast cancer resistance protein, organic cation transporters and members
      of the organic anion polypeptide family. In this communication, the P
      glycoprotein mediated intestinal secretion of talinolol, a model compound showing
      metabolic stability, has been investigated in the jejunum, ileum and colon of rat
      intestine by single-pass perfusion. A model has been developed which demonstrates
      an increase in carrier-mediated secretion in the order jejunum<ileum<colon.
      Furthermore, the potency of common excipients in peroral drug products towards
      inhibition of P-gp mediated secretion has been investigated using a radioligand
      binding assay and transport studies in Caco-2 cell monolayers. Finally, evidence
      is provided which demonstrates that constituents of grapefruit juice not only may
      influence intestinal drug metabolism, but can also interfere with secretory
      transport systems, leading to a new and yet undescribed mechanism in drug-food
      interactions.

PMID- 11576694
TI  - Pharmacogenomics of drug transporters: the next drug delivery challenge.
AB  - Scientifically, the third millennium begins with a major triumph--the publishing
      of the human genomic map, which is destined to have a momentous impact on the
      quality of life in our time. Disease prevention, individualized medicine, and
      genotyped-based medicine will soon become a reality. Pharmacogenetics, the
      forerunner of pharmacogenomics, began in the 1950s with a series of observations
      relating drug response to various genetic factors. It took almost two more
      decades for scientists to discover that cytochrome p450 2D6 was responsible for
      the metabolism of many drugs. This landmark discovery helped focus attention on
      how gene expression could impact the response to drugs. The stage was set for a
      revolution in therapeutics some 30 years later as the Human Genome Project
      crossed the finishing line triumphantly. A parallel development in drug delivery
      that may also benefit from the fruits of the Human Genome Project is the growing
      acceptance/awareness of drug transporters as a gateway to epithelial drug
      transport. This presentation addresses an area in need of attention: the possible
      impact of genetic polymorphism of drug transporters in pharmacokinetics and the
      challenge it poses in drug delivery.

PMID- 11576695
TI  - Predicting the impact of physiological and biochemical processes on oral drug
      bioavailability.
AB  - Recent advances in computational methods applied to the fields of drug delivery
      and biopharmaceutics will be reviewed with a focus on prediction of the impact of
      physiological and biochemical factors on simulation of gastrointestinal
      absorption and bioavailability. Our application of a gastrointestinal simulation
      for the prediction of oral drug absorption and bioavailability will be described.
      First, we collected literature data or we estimated biopharmaceutical properties
      by application of statistical methods to a set of 2D and 3D molecular
      descriptors. Second, we integrated the differential equations for an advanced
      compartmental absorption and transit (ACAT) model in order to determine the rate,
      extent, and approximate gastrointestinal location of drug liberation (for
      controlled release), dissolution, passive and carrier-mediated absorption, and
      saturable metabolism and efflux. We predict fraction absorbed, bioavailability,
      and C(p) vs. time profiles for common drugs and compare those estimates to
      literature data. We illustrate the simulated impact of physiological and
      biochemical processes on oral drug bioavailability.

PMID- 11576696
TI  - Transcytosis of nanoparticle and dendrimer delivery systems: evolving vistas.
AB  - The translocation of particulate matter across the gastrointestinal tract is now
      a well documented phenomenon offering new potential for the delivery of drugs
      with poor dissolution profiles and labile chemistries via encapsulation in
      biodegradable nanoparticles. The last few years have seen an acceleration in the
      number of publications describing the varying facets of this approach and the
      multidisciplinary nature of this field. This review delineates data from this
      rather fragmented area and from cognate fields to provide a physicochemical
      viewpoint of the importance of surface chemistries of oral drug delivery vehicles
      and their interactions in and with gut contents prior to uptake. The role of
      lymphoid and non-lymphoid tissues is examined, and the role of bioadhesion is
      discussed. The exciting potential of molecular encapsulation of drugs via
      dendrimers and star branched molecules is discussed in the context of
      nanotechnological applications for the oral route. Evolving vistas include a
      better understanding of the plasticity of the intestinal epithelium and M-cell
      induction as well as the influence of disease states on particulate uptake. In
      this review we address a number of issues deemed vital to an understanding of the
      subject including (i) some background knowledge on particulate uptake (the
      subject of several reviews), (ii) factors affecting uptake such as diameter and
      surface charge and character, (iii) the dynamic nature of particle interactions
      in the gut, (iv) the dynamic nature of the processes of capture, adhesion,
      uptake, transcytosis and translocation, and (v) the influence of surface ligands.

PMID- 11576697
TI  - Chitosan and its derivatives as intestinal absorption enhancers.
AB  - Chitosan is a non-toxic, biocompatible polymer that has found a number of
      applications in drug delivery including that of absorption enhancer of
      hydrophilic macromolecular drugs. Chitosan, when protonated (pH<6.5), is able to
      increase the paracellular permeability of peptide drugs across mucosal epithelia.
      Chitosan derivatives have been evaluated to overcome chitosan's limited
      solubility and effectiveness as absorption enhancer at neutral pH values such as
      those found in the intestinal tract. Trimethyl chitosan chloride (TMC) has been
      synthesized at different degrees of quaternization. This quaternized polymer
      forms complexes with anionic macromolecules and gels or solutions with cationic
      or neutral compounds in aqueous environments and neutral pH values. TMC has been
      shown to considerably increase the permeation of neutral and cationic peptide
      analogs across Caco-2 intestinal epithelia. The mechanism by which TMC is
      enhancing the intestinal permeability is similar to that of protonated chitosan.
      It reversibly interacts with components of the tight junctions, leading to
      widening of the paracellular routes. This chitosan derivative does not provoke
      damage of the cell membrane, and does not alter the viability of intestinal
      epithelial cells. Co-administrations of TMC with peptide drugs were found to
      substantially increase the bioavailability of the peptide in both rats and
      juvenile pigs compared with administrations without the polymer.

PMID- 11576698
TI  - From interaction of lipidic vehicles with intestinal epithelial cell membranes to
      the formation and secretion of chylomicrons.
AB  - Lipophilic drugs are carried by chylomicrons that are secreted by the small
      intestine and transported in lymph. This review discusses the digestion, uptake,
      and transport of dietary lipids and the impact that these processes have on the
      absorption of lipophilic drugs by the gastrointestinal tract. This chapter
      complements Dr. Chris Potter's chapter on the "pre-absorptive" events of drug
      processing and solubilization. This chapter reviews the digestion of lipids in
      the gastric and intestinal lumen and the role of bile salts in the solubilization
      of lipid digestion products for uptake by the gut. Both the passive and active
      uptake of lipid digestion products is discussed. How intestinal lipid
      transporters located at the brush border membrane may play a role in the uptake
      of lipids by the enterocytes is examined, as is the regulation of the absorption
      of cholesterol by the human ATP-binding cassette transporter-1 (ABC1). The
      intracellular trafficking and the resynthesis of complex lipids from lipid
      digestion products are explored, and the formation and secretion of chylomicrons
      are described.

PMID- 11576699
TI  - In vitro assessment of oral lipid based formulations.
AB  - In recent years there has been an increase in interest in the utility of lipid
      based delivery systems, at least in part as a result of the effective development
      of lipid based products such as Sandimmun Neoral (cyclosporin), Norvir
      (ritonavir) and Fortovase (saquinavir). The development pathway for lipid based
      formulations, however, is still largely empirical, and in vitro models that are
      predictive of oral bioavailability enhancement are lacking. The use of modified
      dissolution media, reflecting the bile salt and phospholipid levels in the
      intestine, has met with some success in terms of the ability to predict the
      bioavailability of poorly water soluble drugs and the potential bioavailability
      enhancing effects of food. These approaches, however, do not have the flexibility
      or complexity to deal with the interactions inherent in the digestion, dispersion
      and solubilisation of a lipid based formulation and the coincident dissolution
      profile of a co-administered drug. In this review, the utility of modified
      dissolution media to predict the impact of food on the absorption of poorly water
      soluble, lipophilic drugs, is explored. These dissolution based systems are
      subsequently contrasted with the use of lipid digestion models which have found
      increasing application in assessment of the interaction of digestible dose forms
      with the gastrointestinal milieu.

PMID- 11576701
TI  - Principles of surgical treatment in localized non-small cell lung cancer.
AB  - Non-small cell cancer has become the leading cause of cancer-related deaths in
      women and men in the western hemisphere. Surgical resection remains the mainstay
      of therapy in stage I and II disease. Surgical therapy has an acceptable
      morbidity and mortality rate. Analysis of 5-year survival shows 70-75% in
      experienced centers for stage I and 40% for stage II, including tumors extending
      to the chest wall. Local and distant recurrence account for the disappointing
      survival rates after complete resection. In the future, appropriate selection of
      surgical procedures and effective use of systemic therapies might depend upon the
      elucidation of prognostic factors that predict recurrence and poor outcome. Thus,
      parameters need to be identified that characterize those patients preoperatively.

PMID- 11576702
TI  - Lung cancer surgery--preoperative risk assessment and patient selection.
AB  - Lung resection remains the therapy of choice offering the greatest potential for
      cure in non spread lung cancer. As these procedures have a significant rate of
      cardiopulmonary complications, risk assessment and evaluation of functional
      operability is essential for successful resectional surgery. The most valuable
      parameters for evaluation of lung function and risk assessment are FEV1, DLCO and
      VO2max as well as the calculation of predicted postoperative lung function. With
      preoperative preparatory physical therapy and treatment of comorbidities, also
      marginal patients may become operable for resectional surgery.

PMID- 11576703
TI  - Prognostic factors in stage I/II non-small cell lung cancer.
AB  - Even in localized stages of non-small cell lung cancer, which are amenable to
      curative surgery, prognosis has remained disappointing over the last decades.
      Thus, in these tumor stages, adjuvant therapy strategies are discussed. In the
      last decade, numerous prognostic factors have been investigated, which might
      select patients for additional treatment. In this review, the prognostic impact
      of individual tumor cell dissemination, tumor cell proliferation, apoptosis,
      several parameters of angiogenesis (microvessel density, VEGF, bFGF, VEGF
      receptors), p53, bcl-2, ras, p27(Kip1), erbB-2, telomerase as well as the
      retinoblastoma tumor suppressor gene is analysed. Up to now, none of these
      factors has gained a sufficient selectivity to serve as an exclusive
      discriminator for adjuvant therapy. Nevertheless, a combination of several
      parameters might contribute to characterize patient subgroups with localized non
      small cell lung cancer at high risk for distant relapse.

PMID- 11576704
TI  - Chemotherapy in stage I+II non-small cell lung cancer.
AB  - Although surgical resection offers the best chance for long-term survival for
      patients with non-small cell lung cancer (NSCLC), the limited number of
      resectable patients and the presence of micrometastatic disease is limiting the
      effectiveness of this modality as sole treatment. Results of randomized trials
      demonstrated a survival benefit for preoperative (neoadjuvant) cisplatin-based
      chemotherapy in patients with stage IIIA NSCLC compared to surgery alone. In
      stage I+II NSCLC preoperative chemotherapy, although still experimental, clearly
      offers encouraging results. However, there is no evidence of its superiority over
      adjuvant chemotherapy. Moreover, for adjuvant therapy a benefit has not been
      established yet. Possibly current ongoing or recently finished trials may change
      the recommendations on adjuvant or neoadjuvant therapy for completely resected or
      resectable early disease in the future.

PMID- 11576705
TI  - Postoperative radiotherapy in localized non-small cell lung cancer.
AB  - Surgery alone can cure 40-85% of patients with localized non-small cell lung
      cancer, depending on tumor stage and metastatic lymph-node involvement. As local
      failure rates occur in up to 50% of the cases, postoperative radiotherapy as an
      adjuvant treatment option has been evaluated in several trials. This review
      briefly summarizes the published data mainly from randomized trials. While most
      of the studies showed a decrease in local recurrence rate, especially in stage
      III/N2 tumors after postoperative radiotherapy, no impact could be shown on
      overall survival. In early stages a detrimental effect of postoperative
      radiotherapy has been postulated, but those findings have to be interpreted with
      caution as radiation techniques used were suboptimal and probably not today's
      state of the art. A carefully designed randomized trial using modern radiotherapy
      techniques is warranted to define the impact of irradiation on completely
      resected NSCLC.

PMID- 11576706
TI  - Dose and fractionation concepts in the primary radiotherapy of non-small cell
      lung cancer.
AB  - At present, radiotherapy alone or in combination with chemotherapy offers the
      only chance of cure of medically inoperable or locally advanced unresectable non
      small cell lung cancer. The radiobiological basis and clinical results of current
      dose and fractionation concepts in the primary radiotherapy of NSCLC are briefly
      reviewed. Whenever possible, focus is given to the results of randomized phase
      III trials. With the exception of early disease treated to doses higher than 60
      Gy, the prognosis of inoperable localized NSCLC is very poor. Local recurrence is
      the major cause of failure after radiation therapy calling for intensified local
      treatment. Dose-escalation using conventional fractionation or moderate
      hypofractionation is promising but randomized trials are presently not available.
      Dose-escalated hyperfractionation theoretically offers advantages, however, there
      appears currently no strong evidence from randomized trials supporting this
      approach in NSCLC. The highly accelerated CHART regimen significantly improved
      survival by 9% compared to standard radiotherapy. Nevertheless, even when treated
      with CHART, about 80% of all patients will eventually develop local recurrence
      and 60% distant metastases. Many trials on combined radiochemotherapy have used
      radiotherapy regimens that are not optimal from a current perspective. Because of
      the high rate of both, local recurrence and distant metastases, future research
      should be directed to further intensify radiotherapy as well as to integrate such
      protocols with systemic treatment in carefully selected patients. Since toxicity
      is expected to increase, state-of-the-art 3D conformal radiation techniques need
      to be part of clinical trials testing such strategies.

PMID- 11576707
TI  - Therapy of localized non-small cell lung cancer (take home messages).
AB  - Surgery remains the mainstay in curative therapy of stage I and II NSCLC and
      selected patients with stage III disease. The high rate of distant metastases
      occurring in patients after complete surgical resection demonstrates the need for
      effective adjuvant systemic therapy. However, outside of trials, (neo)adjuvant
      chemotherapy is currently not considered as an established standard in localized
      NSCLC. Postoperative radiotherapy increases local tumor control in completely
      resected N2 disease and after R1/R2 resections and is generally recommended in
      these situations. In inoperable patients radiotherapy offers the only chance of
      cure. Combined radiochemotherapy and the highly accelerated CHART radiotherapy
      have been shown to be superior to standard radiotherapy. Progress in the
      treatment of localized NSCLC over the last decades has been only modest and with
      the exception of favourable subgroups, prognosis of NSCLC remains grim. In the
      light of the high rate of local and distant metastases multidisciplinary
      approaches appear necessary in the vast majority of patients.

PMID- 11576708
TI  - Preoperative treatment strategies in stage III non-small cell lung cancer.
AB  - Recent experience has emphasized the need to include systemic chemotherapy in
      combined-modality management of locally advanced non-small cell lung cancer stage
      III. If definitive surgery is planned in these situations, preoperative
      application of drugs-induction chemotherapy-has many advantages in comparison to
      postoperative delivery. Patients' compliance to treatment, achievable dose
      intensities of drugs, possible locoregional downstaging, and frequent
      postoperative problems following complex resections are some of the arguments
      favouring preoperative chemotherapy. Despite numerous phase-II investigations,
      little evidence from randomized phase-III trials has been generated. Early
      inclusion of radiotherapy prior to definitive resection may help to improve
      preoperative downstaging. Besides available mature phase-II data, phase-III
      results from ongoing randomized trials are lacking to define the overall value of
      such a complex approach. Important issues in the future will aim at
      individualizing these intensive programs according to findings in clinical
      prognostic factor analyses and to prospectively validate a prognostic risk
      stratification. Data from translational and molecular research may further help
      to develop such evidence-based guidelines.

PMID- 11576709
TI  - Sequential chemo-radiotherapy in non-small cell lung cancer.
AB  - Locally advanced non-small cell lung cancer (NSCLC) stage IIIA/IIIB represents
      approximately 30% of NSCLC and still has a poor prognosis. In this article we
      give a short review on several randomized phase III trials that showed a slight
      but significant survival benefit for sequential chemo-radiotherapy in the
      treatment of locally advanced NSCLC.

PMID- 11576710
TI  - Concomitant radiochemotherapy of advanced non-small-cell lung cancer.
AB  - Concurrent radiochemotherapy (RCT) is a promising new therapy option in advanced
      non-small cell lung cancer (NSCLC). In randomized trials concomitant RCT has been
      shown to be superior compared to radiotherapy alone and to sequential
      radiochemotherapy. In most treatment schedules platinum salts alone or in
      combination with etoposide, mitomycin C or vinca-alkaloids have been used. Up to
      now altered fractionation schemas-particularly hyperfractionated radiotherapy
      have not been demonstrated to be superior to conventional fractionation (2 Gy
      daily up to 56-60 Gy), when employed concurrently to chemotherapy. Nevertheless
      open questions remain: (1) What is the best chemotherapy administered
      simultaneously to radiotherapy? (2) Might newer drugs (e.g. taxanes, inhibitors
      of topoisomerase I and II, gemcitabine) be more effective and reveal fewer side
      effects compared to platinum salts? (3) Is there a role for adjuvant chemotherapy
      following RCT? (4) What is the most effective radiotherapy schedule in concepts
      with RCT? (5) What radiation dose is necessary to optimize local control in RCT?

PMID- 11576711
TI  - Oxygenation of human tumors--implications for combined therapy.
AB  - Recent studies show that the presence of hypoxia is associated with poor local
      control and overall survival in patients with cervical cancer and head and neck
      cancer. An indirect support for the influence of hypoxia on radiation response is
      derived from observations of a correlation between tumor control and hemoglobin
      level. Most of the clinical studies have shown better tumor control in patients
      with higher hemoglobin levels than in patients with levels below normal range due
      to tumor associated or therapy-induced anemia. The problem of chemotherapy
      induced anemia is particularly of clinical relevance in patients with lung
      cancer. This manuscript reviews the clinical investigations in patients with lung
      cancer which have been performed with regard to improve tumor oxygenation
      increasing the amount of hemoglobin available to transport oxygen.

PMID- 11576712
TI  - Trends and perspectives in multimodality therapy of locoregionally advanced non
      small cell lung cancer.
AB  - In recent years progress has been made in the therapy of patients with stage III
      non-small cell lung cancer. Induction chemotherapy and concomitant
      chemoradiotherapy have been proven to be superior to radiation therapy alone for
      unresectable stage disease. In direct comparisons of induction and concomitant
      chemoradiotherapy, the latter has been found to lead to higher median survival
      times, albeit at the cost of increased toxicity within the irradiated field.
      Additional trials have explored the administration of both induction chemotherapy
      and concomitant chemoradiotherapy in sequence and the integration of the taxanes,
      gemcitabine and vinorelbine and irinotecan into the multimodality therapy
      setting. These and other novel concepts are discussed.

PMID- 11576713
TI  - Development of treatment strategies in locally advanced non-small cell lung
      cancer (take home messages).
AB  - In the last decade combined modality treatment approaches contributed to the
      progress of therapy in locally advanced non-small cell lung cancer. With this
      management strategies younger patients (<70 years) with locally advanced disease
      and a good performance status (ECOG 0,1) have survival benefits compared to sole
      locoregional treatment. Further development of these treatment concepts is
      warranted. To adopt optimal tailored therapy to prognostic consistent patient
      groups exact staging of disease is mandatory. Moreover, refinements of the
      staging system would be helpful to identify in defined anatomical stages, patient
      subgroups who will benefit from systemic treatment options different from
      chemotherapy (i.e. tyrosine kinase-inhibition of the epidermal growth factor
      receptor family, anti-angiogenic treatment). The current status of developing
      treatment strategies in locally advanced non-small cell lung cancer is discussed.

PMID- 11576714
TI  - Chemotherapy as treatment of primary and recurrent small cell lung cancer.
AB  - Chemotherapy is the treatment of choice in metastatic stage of small-cell lung
      cancer (SCLC). Radiation therapy, surgery and other forms of therapy are only
      included in special treatment situations, particularly for different local
      problems. A wide range of chemotherapeutic agents have proven to be effective in
      SCLC, including carboplatin, cisplatin, cyclophosphamide, doxorubicin,
      epirubicin, etoposide, ifosfamide, teniposide and vincristine. However, treatment
      results could not be improved over the last 10 years and the median survival of
      patients with metastatic disease is limited to 7-10 months. New agents like
      docetaxel, gemcitabine, irinotecan, paclitaxel, topotecan and vinorelbine have
      shown promising results in phase-II investigations. Yet, no evidence is provided
      from randomized trials to employ these drugs in first line treatment. Clearly,
      polychemotherapy is superior to single agent treatment. Compared to the
      combination of cisplatin and etoposide, no other combination has clearly shown
      improved results in large phase-III randomised trials, yet. The combination of
      cisplatin and irinotecan has also shown promising results in a single randomised
      trial with the need to be confirmed in larger settings. Neither extending the
      initial treatment beyond the median number of six cycles, nor maintenance
      treatment have-so far-resulted in any increase in survival results for patients
      with metastasised SCLC. Nor has dose-intensification, which causes significantly
      higher toxicities in patients, shown a clear impact on the overall survival of
      these patients. Brain metastases represent a high frequent complication
      associated with SCLC. In these cases, the combination of chemotherapy and whole
      brain radiation therapy is advocated. Second-line treatment should always be
      considered in patients with relapse or failure to first-line therapy. In addition
      to a rechallenging with the prior drug combination or selecting a different
      potentially non-cross resistant one, monotherapy with topotecan proved to be
      effective as well. In summary, up to now, no standard chemotherapy combination
      exists for metastatic SCLC. The individual therapy strategy can only be selected
      by considering the clinically relevant conditions of the patient.

PMID- 11576715
TI  - Indications for chemotherapy in stage IV non-small cell lung cancer.
AB  - Treatment of stage IV NSCLC has been a controversial issue during the last
      decade. However, there is now clear evidence that cisplatin-containing
      chemotherapy regimens lead to prolonged survival with an increase of the 1-year
      survival rates at about 10%. New drugs like gemcitabine, the taxanes (paclitaxel,
      docetaxel), and vinorelbine have shown very promising single-agent activity and
      have been included into modern combination chemotherapy regimens achieving
      response rates of 40 to 50% and 1-year survival rates of between 30 and 40%. In
      comparison to single-agent cisplatin or cisplatin/etoposide as 'standard
      treatment approaches', most of these modern combinations could demonstrate
      advantages in terms of response, survival and improved QOL. Patients with
      favourable prognostic factors are at the moment frequently treated with platinum
      based combination chemotherapy often including one of these newer active drugs.
      Patients with adverse prognostic factors such as elderly or stage IV patients
      with a reduced performance status are preferably treated with single agents such
      as gemcitabine, paclitaxel or vinorelbine.

PMID- 11576716
TI  - Influence of age and comorbidities on the chemotherapeutic management of lung
      cancer.
AB  - More than 60% of all patients with cancer are currently older than 65 years.
      Correspondingly, the peak of lung cancer incidence is reached in the age group
      between 75 and 80 years. As a consequence to this ageing patient population,
      three factors become of major importance for the chemotherapeutic management of
      lung cancer, namely functional status, age-specific phenomenon and the presence
      of comorbidities. While the functional status is dependent on physiological
      changes in organ function, ageing-specific phenomena include depression,
      alterations of mental status, reduced nutritional status and missing social
      support. Comorbidities frequently have a risk profile comparable to that of lung
      cancer. Clinical studies with a special focus on elderly patients are still rare.
      In small-cell lung cancer retrospective analyses have demonstrated that age alone
      is not a major prognostic factor compared to performance status, tumor stage or
      gender. Nevertheless elderly patients with lung cancer are still frequently
      excluded from clinical trials, and receive less optimal or even no
      chemotherapeutic treatment at all. Studies evaluating less aggressive treatment
      figured out that single agent therapy with etoposide is inferior compared to
      combination chemotherapy in patients with small cell lung cancer (SCLC). In
      elderly patients with non-small cell lung cancer (NSCLC), single agent treatment
      with vinorelbine plus 'Best Supportive Care' was significantly superior to 'Best
      Supportive Care (BSC)' alone; with respect to survival and symptom palliation.

PMID- 11576717
TI  - Chemotherapy in stage IV lung cancer (take home messages).

PMID- 11576718
TI  - Dose intensive chemotherapy in small cell lung cancer.
AB  - The rationale for treatment intensification is to overcome the occurrence of drug
      resistance and to improve the outcome in SCLC. Several different approaches have
      been tested in the past two decades. Increasing the dose of conventional
      chemotherapy has failed to improve survival in extensive stage. In limited stage
      patients one randomized trial demonstrated a significant survival advantage by a
      20% increase of the dose of cisplatin and cyclophosphamide given during the first
      cycle of chemotherapy. Shortening treatment intervals is achievable by weekly
      chemotherapy or by use of hematopoietic growth factors. Neither weekly
      chemotherapy, tested in four randomized trials, nor the application of
      hematopoietic growth factors significantly improved survival. However, two
      studies described a better survival for patients receiving chemotherapy in
      shorter treatment intervals. In one trial a 3-week interval was superior to a 4
      week interval, and in a second one a 2-week interval superior to a 3-week
      interval. One smaller study, comparing a 4-week interval with a 2-week interval
      with stem cell augmentation by whole blood, revealed no difference in survival
      between both groups. A randomized trial comparing chemotherapy in intervals as
      short as possible with or without growth factor application showed no difference
      for the two groups. Thus, growth factor application seems not to be essential for
      treatment in short intervals and was not associated with superior survival in
      randomized trials. To achieve a more than two-fold increase in dose intensity
      some kind of stem cell support is mandatory. Several phase II trials with small
      patient numbers tested the concept of late intensification with bone marrow
      support in the 1980s. These trials did not show any convincing benefit. There is
      one randomized trial available testing the late intensification approach in which
      a superior progression free survival and a trend for better survival was
      demonstrated, but this difference was not statistically significant due to a high
      mortality rate and a substantial number of local relapses in the high dose arm.
      Newer concepts involving high dose therapy are combining high dose strategies
      with approaches for better local tumor control, administer high dose regimens
      earlier in the treatment course, or use multiple sequential high dose cycles.
      With these approaches 3-year survival rates of up to 40% have been reported. So
      up to date, the superiority of an intensified treatment strategy has not been
      demonstrated in a convincing way and further controlled trials will be necessary
      to clarify the role of dose intense chemotherapy in SCLC.

PMID- 11576719
TI  - Role of radiotherapy in small cell lung cancer.
AB  - Traditionally, small cell lung cancer has been considered as a disease with early
      onset of distant metastases. Therefore, the role of locoregional therapy
      (radiotherapy or surgery) was thought to be very limited. This was supported by
      the first trials investigating the role of radiotherapy since there was no
      improvement of median survival. Recently, two meta-analyses changed this point of
      view: radiotherapy is essential to achieve long term survival. The possible
      biological explanation may be that uncontrolled distant metastases may cause the
      death of patients during the first months of their disease. The longer patients
      survive the more important local therapy becomes. Today, there is growing
      acceptance that adequate systemic and local therapy contributes to better
      treatment results of limited small cell lung cancer.

PMID- 11576720
TI  - Thoracic radiotherapy in the treatment of limited disease of small-cell cancer:
      sequence and fractionation.
AB  - Since two meta-analyses showed improved survival rates at 3 years of
      approximately 5%, thoracic radiotherapy is accepted as an essential component of
      optimal management of limited-disease. However, optimal sequencing, timing,
      fractionation, dose, and field size still remain a matter of controversy. The
      issue has changed since the traditional doxorubicin-based chemotherapy has been
      substituted by cisplatin based regimens which clearly produce less acute toxicity
      and allow concomitant chemoradiation protocols. Up-front radiotherapy seems to
      improve 5-years survival rates compared to the traditional sequential modality.
      Different fractionation schedules and escalated total doses are tested
      prospectively in order to reduce the intrathoracic relapse rate. Increased
      intensity of intrathoracic radiotherapy seems to augment long term survival
      rates.

PMID- 11576721
TI  - Can surgery improve local control in small cell lung cancer?
AB  - Current therapy for small cell lung cancer (SCLC) consists of chemotherapy with
      or without radiotherapy. Radiotherapy is generally accepted as an essential
      treatment component of limited stage disease. However, the local failure rate
      after chemo- and radiotherapy is still high and ranges from 30 to 70%.
      Furthermore, despite having obtained a complete radiographic response, up to 75%
      of these patients will have residual disease in the tumor specimen, if resection
      is performed. Therefore, more effective means are needed to eradicate the primary
      tumor and to obtain an improved local disease control. Recent phase two trials of
      multimodal regimens for stage I-IIIA SCLC demonstrate that in selected patients
      with early stage SCLC the combination of surgery and chemotherapy with or without
      radiotherapy is feasible with low morbidity and mortality rates. The combination
      therapy results in satisfying long term outcome depending on the pathological
      tumor stage and a local disease control is achieved in almost all patients. It is
      remarkable that the pneumonectomy rate has decreased over the past decades from
      almost 100 to 27-39%. In order to confirm these promising results, a German
      multicenter prospective randomized phase III trial has been designed for patients
      with stage I-IIIA SCLC consisting of induction chemotherapy, followed by surgery,
      adjuvant thoracic radiotherapy and prophylactic cranial radiation compared to
      thoracic radiotherapy and prophylactic cranial radiation.

PMID- 11576722
TI  - The role of prophylactic cranial irradiation in the treatment of lung cancer.
AB  - Patients with lung cancer face concurrent risks of their disease by local,
      regional as well as distant failure. The brain is one of the major sites of
      distant relapse and the prevention of cerebral metastasis has therefore gained
      rising interest. A recent meta-analysis has confirmed the benefit of prophylactic
      cranial irradiation in patients with limited disease small-cell lung cancer in
      complete remission following induction therapy. In non-small-cell lung cancer,
      aggressive multimodality therapy regimens including surgery have achieved
      locoregional control rates of 50% and higher. In these patient groups the
      relatively high incidence of brain relapses as a site of first failure causes
      substantial morbidity and worsens the prognosis. Given the proven efficacy of
      prophylactic cranial irradiation (PCI) to prevent metastases to the brain, the
      introduction of PCI into the treatment of non-small cell lung cancer in the
      curative setting seems promising.

PMID- 11576723
TI  - Therapy of small cell lung cancer without distant metastases (take home
      messages).

PMID- 11576724
TI  - Results on single cell PCR for Huntington's gene and WAVE product analysis for
      preimplantation genetic diagnosis.
AB  - Triple repeat base pair amplification is the basis for a number of prevalent
      genetic diseases such as Huntington's, Fragile X, Myotonic Dystrophy and others.
      We have chosen to investigate the use of PCR to amplify a portion of the
      Huntington's gene in single cells in order to develop a clinical test system for
      preimplantation genetic diagnosis (PGD). Amplification of CAG triple repeat
      sequences poses difficulties due to resistance of GC melting for amplification.
      Special PCR modifications are necessary to carry out the amplification of GC rich
      areas found in most triple base pair expansions. We have used a modified
      polymerase chain reaction (PCR) protocol to amplify the expanded repeat sequence
      of the Huntington's gene with satisfactory efficiency. Detection of the amplified
      expanded CAG repeats is shown to be possible using both agarose gel
      electrophoresis and high definition denaturing high pressure liquid (DHPLC)
      chromatography. The incidence of allele dropout (ADO) is documented.

PMID- 11576725
TI  - Using MF-PCR to diagnose multiple defects from single cells: implications for
      PGD.
AB  - Single cell genetic analysis is generally performed using PCR and FISH. Until
      recently, FISH has been the method of choice. FISH however is expensive, has
      significant misdiagnosis rates, can result in interpretation difficulties and is
      labour intensive making it unsuitable for high throughput processing. Recently
      fluorescent PCR reliability has increased to levels at or surpassing FISH whilst
      maintaining low cost. However, PCR accuracy has been a concern due to allelic
      dropout. Multiplex PCR can now increase accuracy by using multiple markers for
      each chromosome to firstly provide diagnosis if markers fail and/or secondly
      confirm diagnosis. We compare a variety of diagnostic methods and demonstrate for
      the first time a multiplex PCR system providing simultaneous diagnosis and
      confirmation of the major aneuploidy chromosomes (21,18,13) and sex as well as
      DNA fingerprint in single cells. We also discuss the implications of using PCR
      for aneuploidy screening in preimplantation genetic diagnosis.

PMID- 11576726
TI  - The in vivo and in vitro efficiency and efficacy of PGD for aneuploidy.
AB  - Preimplantation genetic diagnosis for aneuploidy was implemented on 1782
      morphologically normal embryos generated in vitro by patients with a poor
      prognosis of pregnancy. Only 592 of them (34%) were diagnosed as chromosomally
      normal. Embryo transfer was accomplished in 240 cycles resulting in 79 clinical
      pregnancies (33%) and an implantation rate of 22.6%. The in vitro efficiency of
      the procedure was established by analysing all the blastomeres obtained from 311
      non transferrable embryos and resulted to be 97.1%. The in vivo efficiency of the
      technique was calculated with the data derived from the prenatal diagnoses by
      examination of the infants at birth and was 97.8%. In consideration of the
      reported inaccuracy rate, patients are still recommended to undergo prenatal
      diagnosis. The transfer of PGD selected embryos in women of advanced reproductive
      age reduces by half the risk of having a trisomic pregnancy.

PMID- 11576727
TI  - Preembryonic diagnosis for sickle cell disease.
AB  - Embryos found to be abnormal during preimplantation genetic diagnosis are
      discarded or analyzed to confirm the diagnosis. The destruction of affected
      embryos is ethically unacceptable to some couples. We developed a preembryonic
      genetic diagnosis, that uses sequential first and second polar body removal,
      followed by oocyte freezing at the pronuclear stage. This was applied in a
      patient at risk of having a child with sickle cell disease, who suffered hyper
      stimulation syndrome. Fourteen oocytes were obtained and tested for the maternal
      sickle cell allele by PCR analysis of the first and second polar body.
      Immediately after procedure of polar body removal, the pronuclear-stage oocytes
      were frozen. Six mutation-free oocytes detected by polar body analysis were then
      thawed, allowed to cleave, and transferred in the two consecutive clinical
      cycles, both resulting in clinical pregnancies, one of which resulted in birth of
      a healthy child. The oocytes predicted to contain abnormal beta-globin gene were
      not further cultured, to avoid formation and discard of the affected embryos. The
      results demonstrate feasibility of preembryonic diagnosis for single gene
      disorders, avoiding the establishment and destruction of mutant embryos.

PMID- 11576728
TI  - Studies on sperm chromosomes in patients with severe male factor infertility
      undergoing assisted reproductive technology treatment.
AB  - The aim of the study was to determine the rate of chromosome abnormalities in
      testicular sperm after intracytoplasmic sperm injection due to severe male factor
      infertility. The study groups included patient with non-obstructive azoospermia
      (n=9), obstructive azoospermia (n=10), Klinefelter's syndrome (n=5) and normal
      controls (n=6, groups I-VI, respectively). The mean serum levels of FSH 17.5+/
      8.2 (P<0.05), 3.5+/-2.6, 29.8+/-13.0 (P<0.05) and 3.1+/-0.4 mIU/ml, respectively.
      The rates of chromosome abnormalities were 19.6% (P<0.001), 8.2% (P<0.001), 6.3
      and 1.6%, respectively. Chromosomes X and Y were significantly more involved in
      the aneuploidy than chromosome 18 in groups I and II. The present findings
      demonstrate a linkage between gonadal failure (high serum FSH levels) and sperm
      chromosome abnormalities. Our findings may explain the increased incidence of
      perinatal sex chromosome abnormalities found in severe male factor patients.
      Patients with non-mosaic Klinefelter's syndrome have comparable risk for sex
      chromosomes aneuploidy as the rest of the patients with azoospermia. Therefore,
      genetic screening during pregnancy or before embryo replacement should be
      carefully considered in severe male factor patient following in vitro
      fertilization (IVF).

PMID- 11576729
TI  - Chromosomal abnormalities in embryos.
AB  - Chromosomal analysis was performed on 1620 embryos generated in vitro by patients
      with a poor prognosis of pregnancy. A diagnosis was yielded in 1596 embryos: 536
      (34%) were euploid and 1060 (66%) carried chromosomal abnormalities. The results
      revealed a strong association between chromosomal abnormalities, cellular stage
      and percentage of fragmentation. In addition, 92% of embryos with multinucleated
      cells were diagnosed mosaics, whereas the presence of cytoplasmic concentration
      was associated to 86% chromosomal abnormalities. The rate of development to
      expanded blastocysts was dependent on both the cleavage stage at the time of
      blastomere biopsy and the chromosomal status of the embryos. The highest
      percentage of blastocyst growth derived from embryos with 7-8 cells on the
      morning of day 3: 68% were generated from euploid embryos and 43% from
      chromosomally abnormal embryos. These findings suggest that morphological
      criteria alone are not sufficient in poor prognosis patients to guarantee the
      best embryo selection.

PMID- 11576730
TI  - Expression of imprinted genes in human preimplantation development.
AB  - Imprinted gene expression in preimplantation development has been extensively
      studied in the mouse. Different imprinted genes vary in their time of onset of
      expression and also in the timing and tissue-specificity of mono-allelic
      expression. We have surveyed a range of imprinted genes for expression, and mono
      allelic expression, in human development. Due to the scarcity of human embryos
      available for research, we first prepared amplified cDNA from replicate samples
      of human oocytes, four-cell, eight-cell and blastocyst stages. We then analysed
      these cDNAs for expression of a range of imprinted genes. Three of six genes
      analysed (SNRPN, PEG1 and UBE3A) are clearly expressed in preimplantation
      embryos. Expression was confirmed by direct analysis of embryos for these genes.
      For one of the expressed genes, SNRPN, we have shown that expression is mono
      allelic from the paternal allele in human preimplantation embryos. This gene is
      also mono-allelically expressed in mouse preimplantation embryos. In our earlier
      work, we investigated the molecular mechanisms governing mono-allelic expression
      of the paternal allele of the Xist gene in preimplantation mouse embryos. We
      found that mono-allelic expression was correlated with differential methylation
      of Xist promoter sites in egg and sperm, and specific binding of a protein only
      to the methylated maternal (egg) allele. However, extension of these studies to
      the human showed that, unlike the mouse, XIST is expressed from both parental
      alleles in human preimplantation embryos. Since perturbation of imprinting is
      associated with disease and tumourigenesis, it is important to know the
      expression profiles of imprinted genes in human embryos and to monitor for normal
      imprinted gene expression with the introduction of new procedures in assisted
      conception.

PMID- 11576731
TI  - Towards a full karyotype screening of interphase cells: 'FISH and chip'
      technology.
AB  - Numerical chromosome aberrations are incompatible with normal human development.
      Our laboratories develop hybridization-based screening tools that generate a
      maximum of cytogenetic information for each polar body or blastomere analyzed.
      The methods are developed considering that the abnormality might require
      preparation of case-specific probes and that only one or two cells will be
      available for diagnosis, most of which might be in the interphase stage.
      Furthermore, assay efficiencies have to be high, since there is typically not
      enough time to repeat an experiment or reconfirm a result prior to fertilization
      or embryo transfer. Structural alterations are delineated with breakpoint
      spanning probes. When screening for numerical abnormalities, we apply a Spectral
      Imaging-based approach to simultaneously score as many as ten different
      chromosome types in individual interphase cells. Finally, DNA micro-arrays are
      under development to score all of the human chromosomes in a single experiment
      and to increase the resolution with which micro-deletions can be delineated.

PMID- 11576732
TI  - Chromosomal abnormalities in the first and second polar body.
AB  - Aneuploidy free oocytes may be pre-selected by testing the first and second polar
      bodies removed from oocytes following their maturation and fertilization. We
      present here our experience on the application of the method in IVF cycles from
      patients of advanced maternal age. Overall, 5590 oocytes were obtained from 917
      cycles and tested by polar body sampling and fluorescent in situ hybridization
      (FISH) analysis using specific probes for chromosomes 13,16,18,21 and 22. FISH
      results were available in 4599 (82.2%) of 5590 oocytes studied, from which
      2077(45.2%) were with aneuploidies. Thirty six point one percent of aneuploidies
      were of the first meiotic origin, and 29.3% of the second meiotic origin. Most
      errors in the first meiotic division were represented by chromatid errors. The
      transfer of embryos deriving from 2014 of 2520 aneuploidy free oocytes in 821
      treatment cycles resulted in 182 (22.2%) clinical pregnancies and 140 healthy
      children born after confirmation of the polar body diagnosis. Polar body testing
      of oocytes provides an approach for pre-selection of aneuploidy free embryos,
      improving pregnancy rate in IVF patents of advanced maternal age.

PMID- 11576733
TI  - Chromosomal abnormalities in sperm.
AB  - The use of FISH (fluorescent in situ hybridization) in decondensed sperm nuclei
      has allowed, during the last decade, to indirectly study the chromosome
      constitution of human spermatozoa. Studies in control populations have been used
      to set up the basal level of aneuploidy for all human chromosomes and, based on
      conservative estimates, the percentage of chromosomally abnormal sperm in the
      general population could be considered to be at least 6.7%. In carriers of sex
      chromosome numerical anomalies and in severe oligozoospermic males (both frequent
      candidates for intracytoplasmic sperm injection), in structural chromosome
      carriers (enrolled in preimplantation genetic diagnosis programs) and in couples
      with recurrent miscarriage, sperm chromosome analyses by FISH could help to
      better establish a reproductive prognosis.

PMID- 11576734
TI  - Preimplantation genetic diagnosis of structural abnormalities.
AB  - Preimplantation genetic diagnosis (PGD) of translocations can be achieved through
      a variety of methods. For female carriers, a possibility is by polar body biopsy
      and analysis of its metaphase chromosomes using painting probes. For male
      carriers or female carriers with terminal breakpoints, metaphase chromosomes can
      also be studied by fusing blastomeres to enucleated oocytes. Otherwise,
      interphase analysis of the translocation can be performed using distal,
      subtelomeric or breakpoint spanning probes. The results obtained after PGD of
      translocations indicate a significant decrease in spontaneous abortions after the
      procedure, a good selection against unbalanced oocytes and embryos, and pregnancy
      rates that depend on the type of translocation involved. Balanced translocations
      occur in 0.2% of the neonatal population, but at a higher rate among infertile
      couples and patients with recurrent abortions. In a recent report, balanced
      translocations were found in 0.6% of infertile couples, 3.2% of couples that
      failed over ten IVF cycles, and 9.2% among fertile couples experiencing three or
      more consecutive first-trimester abortions (Hum. Reprod. 14 (1999) 2097). They
      were also found in 2-3.2% of males requiring ICSI (Hum. Reprod. 11 (1996) 2609;
      Hum. Reprod. 13 (1998) 576). PGD can be offered to carriers of balanced
      translocations as an alternative to prenatal diagnosis and pregnancy termination
      of unbalanced fetuses. In recent years, PGD for structural chromosome
      abnormalities has been attempted by a variety of approaches. The aims of PGD for
      translocations are to reduce the rate of spontaneous abortions that this
      population suffers and to minimize the risk of conceiving an unbalanced baby.

PMID- 11576735
TI  - Chromosomal abnormalities in oocytes.
AB  - Since the beginning of in vitro fertilization (IVF), basic research has provided
      insight in the field of human reproduction, especially in genetics. Indeed, the
      contribution of chromosomal abnormalities to oocyte disorders and impaired
      embryonic development is now well known. Of oocytes that fail to fertilize after
      in vitro insemination, 26.5% have been found to be abnormal, with 13.3% showing
      hypohaploidy, 8.1% hyperhaploidy, 1.6% structural abnormalities and 3.5%
      diploidy. The total incidence of abnormalities seems to be correlated with the
      fertility status of the woman. It is higher in oocytes from women with tubal or
      unexplained infertility than in those from women whose husband's infertility is
      the sole cause of infertility in the couple. Although few oocytes recovered
      during natural cycles have been studied, gonadotropins, which are widely used to
      stimulate follicle growth and ovulation, do not increase the risk of
      abnormalities. The effect of maternal age on fetal aneuploidy, well documented at
      birth, has not been unambiguously shown to result from an increase in the
      frequency of aneuploid oocytes. Intra- and extra-follicular influences
      (perifollicular microvasculature, oxygenation, and the presence of residues from
      cigarette smoke) may disturb maturation, leading to immaturity and aneuploidy.
      Thus, oocyte meiosis is very sensitive to endogenous and exogenous factors that
      could result in oocytes with chromosomal abnormalities and therefore, abnormal
      zygotes.

PMID- 11576736
TI  - Reliability of preimplantation diagnosis for single gene disorders.
AB  - Reliability of preimplantation genetic diagnosis (PGD) depends on controlling one
      of the most important limitations of single cell PCR, undetected allele drop out
      (ADO), which may lead to misdiagnosis. To avoid this we introduced mutation
      analysis simultaneously with linked polymorphic markers, pre-selecting only those
      embryos whose unaffected status could be confirmed by at least one linked
      polymorphic marker. We applied this strategy for testing 1047 oocytes, from which
      237 unaffected ones were pre-selected for transfer back to patients, resulting in
      34 unaffected pregnancies and birth of 23 healthy children. Embryos originating
      from mutant oocytes and those with insufficient marker information were followed
      up by multiplex PCR to confirm single cell PCR diagnosis. Of 75 (8.5%) detected
      ADO, only seven (under 1%) were missed in the actual PGD, demonstrating high
      reliability of PGD (98%) based on multiplex single cell PCR.

PMID- 11576737
TI  - Changing indications for preimplantation genetic diagnosis (PGD).
AB  - Preimplantation genetic diagnosis (PGD) is an attractive addition to prenatal
      genetic diagnosis. Not only were traditional PGD indications valid, but newer
      indications should be envisioned. The major new indication is aneuploidy testing
      by PGD for transfer of euploid embryos. This could increase fertilization success
      in ART, and extend to couples experiencing repeated IVF failures or repeated
      spontaneous abortions. Other novel indications can be envisioned for the future.

PMID- 11576738
TI  - PGD in the lab for triplet repeat diseases - myotonic dystrophy, Huntington's
      disease and Fragile-X syndrome.
AB  - Myotonic dystrophy (DM), Huntington's disease (HD) and Fragile X syndrome (FRAXA)
      are three monogenic disease which are caused by so-called dynamic mutations.
      These mutations are caused by triplet repeats inside or in the vicinity of the
      gene which have the tendency to expand beyond the normal range thus disrupting
      the normal functioning of the gene. We describe here our experiences from 1995 to
      May 2000 with PGD for these three triplet repeat diseases.

PMID- 11576739
TI  - Complex regional pain syndrome: how to resolve the complexity?

PMID- 11576740
TI  - The role of fear-avoidance beliefs in acute low back pain: relationships with
      current and future disability and work status.
AB  - Fear-avoidance beliefs have been identified as an important psychosocial variable
      in patients with chronic disability doe to low back pain. The importance of fear
      avoidance beliefs for individuals with acute low back pain has not been explored.
      Seventy-eight subjects with work-related low back pain of less than 3
      weeks'duration were studied. Measurements of pain intensity, physical impairment,
      disability, nonorganic signs and symptoms, and depression were taken at the
      initial evaluation. Fear-avoidance beliefs were measured with the work and
      physical activity subscales of the Fear-avoidance Beliefs Questionnaire.
      Disability and work status were re-assessed after 4 weeks of physical therapy.
      Patterns of correlation between fear-avoidance beliefs and other concurrently
      measured variables were similar to those reported in patients with chronic low
      back pain. Fear-avoidance beliefs did not explain a significant amount of the
      variability in initial disability levels after controlling for pain intensity and
      physical impairment. Fear-avoidance beliefs about work were significant
      predictors of 4-week disability and work status even after controlling for
      initial levels of pain intensity, physical impairment, and disability, and the
      type of therapy received. Fear-avoidance beliefs are present in patients with
      acute low back pain, and may be an important factor in explaining the transition
      from acute to chronic conditions. Screening for fear-avoidance beliefs may be
      useful for identifying patients at risk of prolonged disability and work absence.

PMID- 11576741
TI  - Differential effects of NMDA and group I mGluR antagonists on both nociception
      and spinal cord protein kinase C translocation in the formalin test and a model
      of neuropathic pain in rats.
AB  - Coincident with nociception, both noxious chemical stimulation of the hind paw
      and chronic constriction injury (CCI) of the sciatic nerve produce an increase in
      protein kinase C (PKC) translocation in the spinal cord of rats. Noxious stimulus
      induced PKC translocation likely depends on glutamate activity at either N-methyl
      D-aspartate (NMDA) receptors or group I metabotropic glutamate receptors
      (mGluR1/5) in the spinal cord dorsal horn. This study compares nociceptive
      responses to, and the alterations in membrane-associated PKC, induced by noxious
      chemical stimulation of the hindpaw and CCI of the sciatic nerve, as well as
      their modulation by both NMDA and mGluR1/5 receptor antagonists. Three groups of
      rats were given a single intrathecal (i.t.) injection of either vehicle,
      dizocilpine maleate (MK-801, 60 nmol), an NMDA receptor antagonist, or (S)-4
      carboxyphenylglycine (S)-4CPG, (150 nmol), an mGluR1/5 antagonist, 10 min prior
      to a 50 microl of 2.5% formalin injection into the ventral surface of one hind
      paw. Another three groups of rats were given twice daily injections of either
      vehicle, MK-801 (30 nmol) or (S)-4CPG (90 nmol) i.t. for 5 days starting 30 min
      before CCI or sham injury of the sciatic nerve. Nociceptive responses were
      assessed for a 60 min period after the formalin injection in the first three
      groups, and tests of mechanical and cold allodynia were performed on days 4, 8,
      12 and 16 after CCI for the latter three groups. Furthermore, changes in the
      levels of membrane-associated PKC, as assayed by quantitative autoradiography of
      the specific binding of [3H]-phorbol 12,13-dibutyrate ([3H]-PDBu) in the dorsal
      horn of the lumbar spinal cord sections, were assessed in formalin-injected rats
      (at 5, 25 and 60 min) and in neuropathic rats 5 days after CCI, treated (as
      above) with vehicle, MK-801 or (S)-4CPG. The results indicate that i.t. treatment
      with MK-801 significantly reduced nociceptive scores in the formalin test and
      also produced a significant suppression of formalin-induced increases in [3H]
      PDBu binding in laminae I-II, III-VI and X of the lumbar spinal cord. In
      contrast, i.t. treatment with (S)-4CPG failed to significantly affect either
      nociceptive behaviours in the formalin test or formalin-induced increases in [3H]
      PDBu binding in laminae I-II and III-VI of the lumbar spinal cord. On the other
      hand, i.t. treatment with either MK-801 or (S)-4CPG produced a significant
      reduction in mechanical and cold hypersensitivity, as well as [3H]-PDBu binding
      in laminae I-II and III-VI of the lumbar spinal cord, after CCI. These results
      suggest that while NMDA, but not mGluR1/5, receptors are involved in
      translocation of PKC and nociception in a model of persistent acute pain, both
      types of receptors influence the translocation of PKC in dorsal horn and
      mechanical and cold allodynia in a model of chronic neuropathic pain.

PMID- 11576742
TI  - Antinociceptive effect of continuous intrathecal administration of endomorphin-1.
AB  - Endomorphin-1 is a novel endogenous opioid peptide with high affinity and
      selectivity for the mu-opioid receptor. Earlier results have shown that it causes
      antinociception in different pain tests, but its effect is short-lasting. The
      purpose of the present study was to investigate the antinociceptive potency of
      continuously administered endomorphin-1 on carrageenan-induced thermal
      hyperalgesia by means of a paw withdrawal test in awake rats. The possible
      interaction between endomorphin-1 and the C-terminal octapeptide of the novel
      endogenous peptide nocistatin (bPNP-3-8P) was examined in the same experimental
      set-up. Continuous administration of endomorphin-1 (0.1, 0.3, 1 or 2 microg/min
      for 60 min) did not influence the paw withdrawal latencies of the normal paws. On
      the inflamed side, endomorphin-1 dose-dependently decreased the thermal
      hyperalgesia during continuous administration. The cessation of administration
      resulted in a gradual decrease in the antinociceptive effect of endomorphin-1.
      bPNP-3-8P (0.003-30 microg, administered cumulatively) significantly decreased
      the heat hyperalgesia at higher doses (3 and 30 microg). Continuous
      administration of bPNP-3-8P (0.03, 0.1 and 1 microg/min) did not potentiate the
      antinociceptive effect of endomorphin-1; instead, it even shortened the duration
      of its effect. The results demonstrate that continuous administration of
      endomorphin-1 is an effective method of inhibiting thermal hyperalgesia in rats.
      Furthermore, the fragment bPNP-3-8P itself has low antinociceptive potency and
      does not potentiate the antinociceptive effect of endomorphin-1 under these
      circumstances.

PMID- 11576743
TI  - Protein kinase A modulates spontaneous activity in chronically compressed dorsal
      root ganglion neurons in the rat.
AB  - Protein kinase A (PKA) can play a critical role in the modulation of neuronal
      excitability. We examined the role of PKA in the modulation of abnormal
      spontaneous activity (SA) originating from the chronically compressed dorsal root
      ganglion (CCD). The L(4) and L(5) dorsal root ganglia (DRGs) were compressed by
      inserting a stainless steel rod into each corresponding intervertebral foramen.
      After 1-14 postoperative days, SA in DRG neurons with myelinated axons was
      recorded in vitro from teased dorsal root microfilaments. Rp-cAMPS (5-500
      microM), a specific inhibitor of PKA, caused a dose-dependent decrease in the
      discharge rate of SA when topically applied to the DRG. The highest dose
      completely blocked the SA, but not the conduction of action potentials. H89 (10
      microM), another PKA inhibitor, also markedly decreased SA. Sp-cAMPS (500
      microM), a specific activator of PKA, increased the discharge rate of SA in all
      injured units tested, but did not trigger firing in silent neurons. Okadaic acid
      (0.1 microM), a protein phosphatase inhibitor, and forskolin (1 microM), an
      adenyl cyclase activator, each significantly increased the discharge rate of SA.
      These results strongly suggest that PKA modulates the SA in injured DRG neurons
      with myelinated axons.

PMID- 11576744
TI  - Nitric oxide synthase in spinal cord central sensitization following intradermal
      injection of capsaicin.
AB  - Nitric oxide (NO) is believed to be an important messenger molecule in signal
      transduction pathways that enhance nociceptive transmission in the central
      nervous system (CNS). The role of nitric oxide synthase (NOS) I and II, which
      synthesize NO, in central sensitization induced by an intradermal capsaicin
      injection was investigated. To elucidate whether changes in NOS I and NOS II
      activities caused by capsaicin injection contribute to behavioral changes,
      responses to von Frey filaments with two different innocuous bending forces
      applied on the rat foot were tested. The allodynic responses induced by capsaicin
      injection in the foot were partially reversed by the administration of either the
      selective NOS I inhibitor, 7-nitroindazole (7-NINA), or the selective NOS II
      inhibitor, 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT). To confirm changes
      at the level of single nociceptive neurons, extracellular recordings were made
      from rat dorsal horn neurons. The electrophysiological results showed that
      increased responses to noxious and innocuous stimuli caused by capsaicin
      injection were blocked by either 7-NINA or AMT delivered through a microdialysis
      fiber inserted through the dorsal horn. Finally, the expression of both NOS I and
      NOS II in the spinal cord as demonstrated by Western blots was increased by 20
      min following intradermal capsaicin injection in the rat foot. These results
      suggest that both NOS I and NOS II are upregulated following intradermal
      capsaicin injection and that both cause NO release that contributes to the
      secondary hyperalgesia and allodynia following this noxious chemical stimulus.

PMID- 11576745
TI  - Enhanced formalin nociceptive responses following L5 nerve ligation in the rat
      reveals neuropathy-induced inflammatory hyperalgesia.
AB  - The development of mechanical and thermal hypersensitivity following peripheral
      nerve injury is well known and a great deal of research has been directed towards
      understanding the mechanisms underlying these phenomena. However, there has been
      very little research examining if hypersensitivity to an inflammatory condition
      following nerve injury also develops. Therefore, the purpose of the present study
      was to determine if hypersensitivity to an inflammatory condition produced in the
      formalin test develops following ligation of the L5 spinal nerve. Male Sprague
      Dawley rats received tight ligation of the L5 spinal nerve or were given sham
      surgery. Following a 14-day recovery period, the threshold to produce a
      withdrawal response to a mechanical stimulus was measured using von Frey
      monofilaments and then formalin behavioral responses were measured. Compared to
      sham animals, L5 ligated animals exhibited significantly lower mechanical paw
      withdrawal thresholds as well as elevated and prolonged nociceptive responses
      during the second phase (20-60 min) of the formalin test. These results reveal
      enhanced inflammatory nociceptive processes following peripheral nerve damage and
      might provide a useful approach to study underlying neural mechanisms associated
      with clinical neuropathic pain syndromes.

PMID- 11576746
TI  - Responses of the supra-sylvian (SII) cortex in humans to painful and innocuous
      stimuli. A study using intra-cerebral recordings.
AB  - In this study we compare the intrinsic characteristics and localization of
      nociceptive CO(2) laser evoked potential (LEP) and non-nociceptive electrical EP
      (SEP) sources recorded by deep electrodes (one to two electrodes per patient, 10
      15 contacts per electrode) directly implanted in the supra-sylvian cortex of 15
      epileptic patients. Early CO(2) laser (N140-P170) and electrical (N60-P90) evoked
      potentials were recorded by all of the electrodes implanted in the supra-sylvian
      cortex contralateral to stimulation. SEPs and LEPs had similar waveforms and
      inter-peak latencies. The LEPs appeared 84+/-15 ms later and were, on average,
      14.2+/-22.2 microV smaller than the SEPs. These differences may be accounted for
      by the characteristics and the sizes of the different peripheral fibers (Adelta
      vs. Abeta) activated by the two types of stimuli. The stereotactic Talairach
      coordinates of the SEP and LEP sources covered the pre- and post-rolandic upper
      bank of the sylvian fissure, and were not significantly different for noxious and
      non-noxious stimuli. The spatial distribution of these contralateral responses
      fits with that of the modeled sources of scalp CO(2) LEPs, magneto
      encephalographic studies, and PET data from pain and vibrotactile activation
      studies. These results permit us to define the SII cortex as a cortical
      integration area of non-nociceptive and nociceptive inputs. This is supported by:
      (i) anatomical data reporting that the SII area receives inputs from both
      posterior columns and spino-thalamic pathways conveying the non-noxious and
      noxious information, respectively, and (ii) single cell recordings in monkeys,
      demonstrating that the SII area contains both nociceptive-specific neurons and
      wide-dynamic-range neurons receiving convergent input from nociceptive and non
      nociceptive somatosensory afferents.

PMID- 11576747
TI  - Prevalence and management of cancer pain in South Africa.
AB  - Inadequate relief from cancer pain is an international health problem. The aim of
      this study was to document the prevalence and patterns of cancer pain management
      in the Republic of South Africa. The first phase of this study consisted of
      screening 263 patients to document the prevalence of cancer pain in varying
      settings. A total of 94 patients were experiencing cancer-related pain; this
      comprised 35.7% of the sample. Inpatients had a higher prevalence than
      outpatients, which is likely due to the fact that these patients are more acutely
      ill. Blacks (56.1%) had a higher prevalence of pain than whites (29.4%, P<0.005);
      this difference was most pronounced in the outpatient setting. Phase 2 consisted
      of asking 426 patients with cancer pain from different settings to complete a
      questionnaire that included the brief pain inventory and was designed to learn
      about their pain and how it was managed. Nearly one-third of the entire sample
      experienced 'worst pain' of severe intensity. There was little difference between
      the public and private cancer care centers. The lowest percentage of patients
      with severe 'worst pain' was in the hospice setting, but even in this group about
      one-fourth of the patients had peak pain that was severe. Of non-whites combined,
      81% experienced 'worst pain' of moderate to severe intensity as compared to 65%
      of whites (P<0.001). Only 21% of patients reported that they had achieved 100%
      pain relief. Patients experienced interference in general activity, mood,
      walking, working, relations with others, sleeping, and enjoyment of life related
      to their pain. 30.5% of the entire sample had a negative score on the pain
      management index, a comparison of the most potent analgesic used by a patient
      relative to their worst pain. Of this group, 58.1% were experiencing severe
      'worst pain'. Unrelieved cancer pain is a significant problem. Government and non
      government leaders, educators, and practitioners must collaborate to address the
      barriers to effective pain management and to implement improvements in education,
      health policy, and health care delivery.

PMID- 11576748
TI  - Pain self-efficacy beliefs and pain behaviour. A prospective study.
AB  - This study examined the relationship between pain self-efficacy beliefs and a
      range of pain behaviours, as measured by the pain behaviour questionnaire (PBQ),
      using a prospective design. A heterogeneous sample of 145 chronic pain patients
      completed sets of questionnaires on four occasions over a nine-month period.
      Multiple hierarchical regression analyses revealed that the subjects' confidence
      in their ability to perform a range of tasks despite pain (assessed at baseline),
      was predictive of total pain behaviour and avoidance behaviour over the nine
      month study period. This finding was particularly significant because the
      analyses controlled for the possible effects of pain severity (at each
      measurement occasion), pain chronicity, age, gender, physical disability,
      depression, neuroticism and catastrophising. These findings suggest that pain
      self-efficacy beliefs are an important determinant of pain behaviours and
      disability associated with pain, over and above the effects of pain, distress and
      personality variables. In particular, higher pain self-efficacy beliefs are
      predictive of reduced avoidance behaviours over an extended period.

PMID- 11576749
TI  - Reversible analgesia, atonia, and loss of consciousness on bilateral
      intracerebral microinjection of pentobarbital.
AB  - Concussion, asphyxia, and systemically administered general anesthetics all
      induce reversible depression of the organism's response to noxious stimuli as one
      of the elements of loss of consciousness. This is so even for barbiturate
      anesthetics, which have only modest analgesic efficacy at subanesthetic doses.
      Little is known about the neural circuits involved in this form of
      antinociception, although for anesthetic agents, at least, it is usually presumed
      that the drugs act in widely distributed regions of the nervous system. We now
      report the discovery of a focal zone in the brainstem mesopontine tegmentum in
      rats at which microinjection of minute quantities of pentobarbital induces a
      transient, reversible anesthetic-like state with non-responsiveness to noxious
      stimuli, flaccid atonia, and absence of the righting reflex. The behavioral
      suppression is accompanied by slow-wave EEG and, presumably, loss of
      consciousness. This zone, which we refer to as the mesopontine tegmental
      anesthesia locus (MPTA), apparently contains a barbiturate-sensitive 'switch' for
      both cortical and spinal activity. The very existence of the MPTA locus has
      implications for an understanding of the neural circuits that control motor
      functions and pain sensation, and for the cerebral representation of
      consciousness.

PMID- 11576750
TI  - Acute pain in herpes zoster: the famciclovir database project.
AB  - The results of a considerable number of recent prospective studies have
      demonstrated that greater acute pain severity in herpes zoster patients is
      associated with a significantly greater risk of developing postherpetic neuralgia
      (PHN). Only a few studies have examined the relationships between acute pain
      severity and demographic characteristics and clinical features of patients with
      herpes zoster, however, and the results of these studies have been inconsistent.
      To clarify these relationships, data from 1778 herpes zoster patients studied
      within 72 h of rash onset in four clinical trials of the antiviral agent
      famciclovir were examined. Univariate and multivariate analyses indicated that
      greater acute pain severity was significantly associated with greater age, female
      sex, greater rash severity, the presence of a prodrome, and primary involvement
      of non-trigeminal dermatomes. These results demonstrate that three of the
      established risk factors for PHN - older age, greater rash severity, and the
      presence of a prodrome - are also associated with more severe acute pain assessed
      soon after rash onset in patients with herpes zoster. The results of this study
      are consistent with the recommendation that herpes zoster patients who are older,
      who have had a prodrome, or who have severe rash or severe acute pain should be
      targeted for interventions designed to prevent PHN.

PMID- 11576751
TI  - Systemic adenosine infusions alleviated neuropathic pain.
AB  - A 15-year-old boy suffering from a degenerative neurometabolic disorder was
      treated in a palliative home care unit. Opioid administered by continuous
      intravenous infusion gave excellent relief from headache, muscle pain and pain
      from renal calculi. He continued to complain of burning pain in response to
      tactile stimuli. A prior quantitative sensory test had shown changes in
      sensation. Intravenous adenosine (ADO) infusions were given weekly. After 5 weeks
      of infusions, there was no recurrence of pain between treatments. ADO infusions
      were continued for 7 months without any side effects or signs of tolerance to the
      drug. There are indications that ADO may play a role as a modulator of
      neuropathic and nociceptive pain. In this case with pronounced allodynia, our
      interpretation is that neuropathic mechanisms were responsible and that ADO
      infusions played an important role in controlling pain.

PMID- 11576752
TI  - Foreword.

PMID- 11576753
TI  - Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood
      disorders. A review and a Western blot study of synaptophysin, GAP-43 and the
      complexins.
AB  - There are several reports of ultrastructural and protein changes affecting
      synapses in the anterior cingulate cortex in schizophrenia. Altered
      cytoarchitecture has also been described in this region in schizophrenia as well
      as in mood disorders. In this paper we review the literature and present a new
      study investigating synaptic abnormalities in the anterior cingulate cortex (area
      24) in the Stanley Foundation brain series. We used Western blotting to assess
      four synaptic proteins: synaptophysin, growth-associated protein-43 (GAP-43),
      complexin I and complexin II, which inform about somewhat different aspects of
      the synaptic circuitry. Synaptophysin, complexin II and GAP-43 were reduced in
      bipolar disorder. The decreases correlated with the duration of illness and
      tended to be greater in subjects without a family history. Complexin II was also
      reduced in major depression. Complexin I and the housekeeping protein beta-actin
      did not differ between groups. None of the proteins changed significantly in
      schizophrenia. The results indicate the presence of a synaptic pathology in the
      anterior cingulate cortex in mood disorders, especially bipolar disorder. The
      abnormalities may contribute to the dysfunction of cingulate neural circuits. The
      loss of synaptophysin is suggestive of decreased synaptic density whilst the
      decrease in GAP-43 may denote impaired synaptic plasticity and the reduction of
      complexin II but not complexin I implies that the alterations particularly affect
      excitatory connections. The reductions may be progressive.

PMID- 11576754
TI  - Neurochemical correlates of cortical GABAergic deficits in schizophrenia:
      selective losses of calcium binding protein immunoreactivity.
AB  - Deficits in a variety of different neurochemical species are consistent with a
      loss of cortical gamma-aminobutyric acid (GABA)ergic interneurons in
      schizophrenia. As well as neurochemical markers that indicate all neurons using
      GABA as a transmitter, and which include GABA uptake sites and glutamate
      decarboxylase, deficits of certain neuropeptides and calcium binding proteins
      coexisting with GABA have been reported. These abnormalities are indicative of
      losses specific to certain subtypes of GABAergic neurons. The calcium binding
      proteins in particular demonstrate selective deficits; we find losses of
      parvalbumin- and calbindin-, but not calretinin-immunoreactive cells in the
      prefrontal cortex in schizophrenia. These selective reductions in the density of
      parvalbumin- and calbindin-containing neurons could reflect functional loss of
      expression in intact cells or alternatively a deficit in the density of certain
      GABAergic neuronal subtypes. The latter interpretation is consistent with a
      neurodevelopmental pathogenesis involving neuronal damage at a time prior to the
      expression of these protective calcium-binding proteins. In this review we
      discuss the evidence for altered GABAergic transmission in schizophrenia.

PMID- 11576755
TI  - Glial cell abnormalities in major psychiatric disorders: the evidence and
      implications.
AB  - Recent quantitative post-mortem investigations of the cerebral cortex have
      convincingly demonstrated cortical glial cell loss in subjects with major
      depression. Evidence is also mounting that glial cell loss may also be a feature
      of schizophrenia. These findings coincide with a re-evaluation of the importance
      of glial cells in normal cortical function. In addition to their traditional
      roles in neuronal migration and inflammatory processes, glia are now accepted to
      have roles in providing trophic support to neurons, neuronal metabolism, and the
      formation of synapses and neurotransmission. Consequently, reduced cortical glial
      cell numbers could be responsible for some of the pathological changes in
      schizophrenia and depression, including reduced neuronal size, reduced levels of
      synaptic proteins, and abnormalities of cortical neurotransmission. Additionally,
      as astrocytes provide the energy requirements of neurons, deficient astrocyte
      function could account for aspects of the functional magnetic imaging
      abnormalities found in these disorders. We discuss the possible basis of glial
      cell loss in these disorders and suggest that elevated levels of glucocorticoids,
      due to illness-related stress or to hyperactivity of the hypothalamic-pituitary
      adrenal may down-regulate glial activity and so predispose to, or exacerbate
      psychiatric illness through enhanced excitotoxicity. The potential therapeutic
      impact of agents which up-regulate glial activity or normalise glial cell numbers
      is also discussed.

PMID- 11576756
TI  - Electron microscopy of oligodendroglia in severe mental illness.
AB  - Qualitative electron microscopy was performed to verify whether brain pathology
      in schizophrenia and bipolar disorder is associated with alterations of
      oligodendroglial cells and myelinated fibers. Ultrastructural signs of apoptosis
      and necrosis of oligodendroglial cells were found in the prefrontal area 10 and
      the caudate nucleus in both schizophrenia and bipolar disorder. Damage of myelin
      sheath lamellae, with the formation of concentric lamellar bodies, were detected
      in both brain structures in schizophrenia. There was also a significant decrease
      in the area of the nucleus and the volume density of mitochondria in
      oligodendrogliocytes in the caudate nucleus and in the prefrontal cortex in
      schizophrenia, as compared to normal controls. Volume density of heterochromatin
      was significantly increased (+14%) in the caudate nucleus in schizophrenia. The
      density of concentric lamellar bodies (as an indicator of damage of myelinated
      fibers) was dramatically increased (4.5-fold) in the caudate nucleus in
      schizophrenia, as compared to controls, and was positively correlated with volume
      density of heterochromatin. Multiple regression analysis and analysis of
      covariance demonstrated that these changes could not be explained by the effects
      of postmortem delay, age, neuroleptic medication, or gender. Pathology of
      oligodendroglia might be an essential feature of severe mental disorders.

PMID- 11576757
TI  - A quantitative immunohistochemical study of astrocytes in the entorhinal cortex
      in schizophrenia, bipolar disorder and major depression: absence of significant
      astrocytosis.
AB  - A number of macroscopic changes have been reported in the temporal lobe in
      schizophrenia. We have evaluated the density of glial fibrillary acidic protein
      (GFAP)-positive astrocytes in cortical layers 2 through 6 in the intermediate
      subarea of entorhinal cortex in two cohorts: the first, 15 cases, made up of
      schizophrenic (n = 7) and normal nonpsychiatric control subjects (n = 8), and the
      second, 56 cases, composed of schizophrenic (n = 14), bipolar disorder (n = 13),
      major depressive (n = 14) and normal control subjects (n = 15). No significant
      difference in density of GFAP-positive astrocytes was detected between the
      psychiatric diagnostic groups and the normal controls in either of the two
      cohorts. In both cohorts there was a positive correlation between increasing age
      and astrocytic density which reached statistical significance in only the larger
      cohort (r = 0.38, p = 0.004). Our results find no evidence for astrocytosis in
      the entorhinal cortex in several mental illnesses. Although other studies have
      reported macroscopic and other structural abnormalities in this region, we have
      not detected astrocytic proliferation, which is a typical hallmark of atrophy
      and/or progressive neuronal loss.

PMID- 11576758
TI  - Prodynorphin and kappa opioid receptor mRNA expression in the cingulate and
      prefrontal cortices of subjects diagnosed with schizophrenia or affective
      disorders.
AB  - The present study examined the prodynorphin and kappa opioid receptor mRNA
      expression levels in the anterior cingulate and dorsolateral prefrontal cortices
      of subjects diagnosed with schizophrenia, bipolar disorder, or major depression
      as compared with normal controls without a psychiatric diagnosis. Multivariate
      analyses failed to reveal any differences in the mRNA expression levels between
      the four diagnostic groups, though a group trend (non-significant) was evident
      for the expression of the kappa opioid receptor and prodynorphin mRNAs in the
      prefrontal cortex. The mRNA expression levels were not associated with lifetime
      history of antipsychotic treatment or with suicide as a cause of death. The
      results, however, suggested an influence of certain drugs of abuse on the
      prodynorphin cortical mRNA expression. Prodynorphin mRNA expression levels were
      found to be elevated in individuals with a history of marihuana or stimulant use,
      but not alcohol. Overall, our data do not provide strong evidence for impaired
      prodynorphin or kappa opioid receptor mRNA levels in the dorsolateral prefrontal
      or cingulate cortices of schizophrenic, bipolar disorder, or major depressed
      subjects.

PMID- 11576759
TI  - Abnormalities in the cAMP signaling pathway in post-mortem brain tissue from the
      Stanley Neuropathology Consortium.
AB  - There is an established relationship between the monoaminergic neurotransmitter
      system and mood disorders. In an attempt to define further the pathophysiology of
      mood disorders, research is focussing on intracellular second messenger systems,
      including cyclic adenosine 3',5'-monophosphate (cAMP) and the polyphosphoinositol
      generated second messengers. The availability of tissue from the Stanley
      Foundation Neuropathology Consortium has offered us the opportunity to make a
      number of observations with respect to these second messenger systems in tissue
      from patients with major depressive disorder and bipolar affective disorder.
      There is evidence that antidepressants stimulate components of the cAMP pathway
      in patients with depression while mood stabilizers blunt the same pathway in
      patients with bipolar disorder. Furthermore, downstream targets of this pathway
      appear to be altered in patients with mood disorders. The relations between
      changes in second messenger systems, gene transcription, and clinical effects of
      current therapeutic regimens has implications for development of novel treatments
      of mood disorders.

PMID- 11576760
TI  - Striatal ionotropic glutamate receptor expression in schizophrenia, bipolar
      disorder, and major depressive disorder.
AB  - Abnormalities of the ionotropic glutamate receptors (N-methyl-D-aspartate, alpha
      amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid [AMPA], and kainate) have
      been reported in the brain in schizophrenia, although in complex, region-specific
      patterns. While limbic cortex and medial temporal lobe structures have been most
      often studied in psychiatric illnesses, glutamate receptors are expressed in
      other brain regions associated with limbic circuitry, especially the striatum. In
      this study, we have determined striatal ionotropic glutamate receptor expression
      in brains from persons with schizophrenia, bipolar disorder, major depression,
      and a comparison group, using samples from the Stanley Foundation Neuropathology
      Consortium. We have determined the expression of these receptors at multiple
      levels of gene expression by using both in situ hybridization and receptor
      autoradiography. The expression of nearly all of these molecules was not
      different in these psychiatric conditions. The only significant changes noted
      were NR2D and gluR1 transcripts, and [(3)H]AMPA binding. This is the first
      comprehensive study of striatal ionotropic glutamate receptor expression in
      schizophrenia and affective disorders, and suggests that there are minimal
      changes in these receptors in this region of the brain in these illnesses.

PMID- 11576761
TI  - Application of cDNA microarrays to examine gene expression differences in
      schizophrenia.
AB  - Using cDNA microarrays we have investigated gene expression patterns in brain
      regions of patients with schizophrenia. A cDNA neuroarray, comprised of genes
      related to brain function, was used to screen pools of samples from the
      cerebellum and prefrontal cortex from a matched set of subjects, and middle
      temporal gyrus, from a separate subject cohort. Samples of cerebellum and
      prefrontal cortex from neuroleptic naive patients were also included. Genes that
      passed a 3% reproducibility criterion for differential expression in independent
      experiments included 21 genes for drug-treated patients and 5 genes for drug
      naive patients. Of these 26 genes, 10 genes were increased and 16 were decreased.
      Many of the differentially expressed genes were related to synaptic signaling and
      proteolytic functions. A smaller number of these genes were also differentially
      expressed in the middle temporal gyrus. The five genes that were differentially
      expressed in two brain regions from separate cohorts are: tyrosine 3
      monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide;
      sialyltransferase; proteasome subunit, alpha type 1; ubiquitin carboxyl-terminal
      esterase L1; and solute carrier family 10, member 1. Identification of patterns
      of changes in gene expression may lead to a better understanding of the
      pathophysiology of schizophrenia disorders.

PMID- 11576762
TI  - Multivariate analysis of prefrontal cortical data from the Stanley Foundation
      Neuropathology Consortium.
AB  - Prefrontal cortical tissue from the Stanley Foundation Neuropathology Consortium,
      which contains samples from patients with schizophrenia, bipolar disorder, non
      psychotic depression, and normal controls (n = 15 per group), was studied in a
      blinded fashion in 14 different laboratories between 1997 and 2000. The results
      of 69 separate data sets were analyzed with univariate and multivariate
      techniques. A total of 17 abnormal markers were identified that pertained to a
      variety of neural systems and processes, including neuronal plasticity,
      neurotransmission, signal transduction, inhibitory interneuron function, and
      glial cells. Schizophrenia was associated with the largest number of
      abnormalities, many of which were also present in bipolar disorder. Major
      depression was associated with relatively few abnormalities. The majority of
      abnormal findings represented a decline in function and could not be easily
      explained by exposure to psychotropic or illicit drugs. It is argued that the
      abnormal findings are not simply due to stochastic processes but represent viable
      markers for independent replication and further study as candidate genes or
      targets for new treatments.

PMID- 11576763
TI  - UV absorption method should not be applied for determining amoxycillin in acidic
      dissolution test medium.
AB  - In order to clarify the suitability of assay method, the stability of amoxycillin
      (AMX) in the acidic solution at pH 1.2 was determined by two different methods,
      ultraviolet absorption (UV) and HPLC methods. The determination was
      simultaneously performed for the same sample solutions. The data from HPLC method
      indicated that AMX degraded and the concentration of AMX in the acidic solution
      was decreased. The apparent first-order rate constant (k(obs)) for the
      degradation was 9.83x10(-2) h(-1), and the half-life was calculated to be 7.04 h.
      On the other hand, the data obtained from UV method apparently represented that
      the concentration of AMX increased with time-course. This phenomena was brought
      about by the increase of UV absorption at 272 nm, which accompanied with the
      degradation of AMX. These results clearly indicate that UV method can not be used
      for determining the samples accompanying the degradation of AMX. In general, the
      dissolution test (drug release test) has been used for the evaluation of a
      sustained-release dosage form of AMX. It is impossible to avoid the degradation
      of AMX in the test under acidic conditions. The results indicated that the UV
      method should not be used for the determination of AMX in the test.

PMID- 11576764
TI  - A critical review of the probable reasons for the poor variable bioavailability
      of rifampicin from anti-tubercular fixed-dose combination (FDC) products, and the
      likely solutions to the problem.
AB  - The problem of poor/variable bioavailability of rifampicin, which is shown in
      particular when the drugs are present in anti-tubercular fixed-dose combination
      (FDC) products, is a matter of serious concern. There is a potential of failure
      of therapy in patients with an active disease. It perhaps also is a contributory
      factor towards the increasing resistance to anti-tubercular drugs. Unfortunately,
      the origin and cause of the problem is not clearly understood, though GMP and
      crystalline changes in the drug are invariably cited as the principal reasons. In
      this write-up, various probable physical and/or chemical reasons are critically
      reviewed. The enhanced decomposition of rifampicin in the presence of isoniazid
      in stomach after ingestion is indicated to be the key factor behind the problem.
      Some simple solutions offered by the knowledge of the cause are discussed and it
      is concluded that there is a need to have a multifaceted approach to handle the
      problem.

PMID- 11576765
TI  - Production of griseofulvin nanoparticles using supercritical CO(2) antisolvent
      with enhanced mass transfer.
AB  - Griseofulvin (GF) is a poor water soluble, antifungal agent. The bioavailability
      of the drug and its absorption from the gastrointestinal tract can be greatly
      improved by particle size reduction. In this work, supercritical antisolvent
      precipitation with enhanced mass transfer (SAS-EM) has been proposed for the
      production of GF nanoparticles. SAS-EM is a modification of the currently
      existing supercritical antisolvent (SAS) precipitation technique and also
      utilizes supercritical CO(2) as the antisolvent. In SAS-EM however, the solution
      jet is deflected by a surface vibrating at an ultrasonic frequency that atomizes
      the jet into small micro droplets. Further, the ultrasound field generated by the
      vibrating surface inside the supercritical media enhances mass transfer and
      prevents agglomeration due to increased mixing. GF nanoparticles of different
      sizes and morphologies have been obtained by varying the vibration intensity of
      the deflecting surface, which in turn is adjusted by changing the power supply to
      the attached ultrasound transducer. GF nanoparticles as low as 130 nm in size
      have been obtained corresponding to a power supply of 180 W. The effect of using
      different solvents on the size and morphology of the particles has also been
      studied.

PMID- 11576766
TI  - Controlled release of antifungal drug terbinafine hydrochloride from poly(N-vinyl
      2-pyrrolidone/itaconic acid) hydrogels.
AB  - Adsorption and controlled release of terbinafine hydrochloride (TER-HCl) to and
      from pH-sensitive poly(N-vinyl 2-pyrrolidone/itaconic acid) P(VP/IA) hydrogels
      were investigated. P(VP/IA) hydrogels were prepared by irradiating the ternary
      monomer mixtures of N-vinyl 2-pyrrolidone/itaconic acid/ethylene glycol
      dimethacrylate in aqueous solution by gamma-rays at ambient temperature.
      Hydrogels containing antifungal drug TER-HCl, at different drug-to-polymer
      ratios, were prepared by direct adsorption method. The influence of IA content in
      the gel on the adsorption capacities of hydrogels and the effect of pH on the
      releasing behavior of TER-HCl from the gel matrix were investigated. Terbinafine
      adsorption capacity of hydrogels was found to increase from 6 to 82 mg of TER-HCl
      per gram of dry gel with increasing drug concentration and amount of IA in the
      gel system. In-vitro drug-release studies in different buffer solutions showed
      that the basic parameters affecting the drug-release behavior of hydrogels are
      the pH of the solution and the IA content of the hydrogel.

PMID- 11576767
TI  - Preparation and in vitro evaluation of liposomal/niosomal delivery systems for
      antipsoriatic drug dithranol.
AB  - Dithranol is one of the mainstays in the topical treatment of psoriasis. However,
      the use of dithranol in psoriatic condition is inconvenient and troublesome, as
      it has irritating, burning, staining and necrotizing effect on the normal as well
      as the diseased skin. The entrapment of drug in vesicles is viewed to help in the
      localized delivery of the drug and an improved availability of the drug at the
      site will reduce the dose and in turn, the dose-dependent side effects like
      irritation and staining. The investigations deal with critical parameters
      controlling the formulation and stabilization of dithranol loaded liposomes and
      niosomes. The entrapment efficiency of dithranol in liposomes was optimized by
      altering the proportion of phosphatidyl choline and cholesterol, and in case of
      niosomes it was between Span 60 and cholesterol. Hydration and permeation mediums
      were also established keeping in view the poor solubility and stability of
      dithranol. The mean liposome and niosomes sizes were 4+/-1.25 and 5+/-1.5 microm,
      respectively. The drug-leakage study carried out at different temperatures of 4
      8, 25+/-2 and 37 degrees C for a period of two months affirms that the drug
      leakage increased at a higher temperature. The in vitro permeation study using
      mouse abdominal skin shows significantly enhanced permeation with vesicles as
      indicated by flux of dithranol from liposomes (23.13 microg/cm(2)/h) and niosomes
      (7.78 microg/cm(2)/h) as compared with the cream base (4.10 microg/cm(2)/h).

PMID- 11576768
TI  - Impaired bioavailability of rifampicin in presence of isoniazid from fixed dose
      combination (FDC) formulation.
AB  - The present study describes comparative bioavailability of rifampicin (RIF) after
      administration of a single component RIF (450 mg) capsule and rifampicin
      isoniazid (RIF-INH) (450+300 mg) fixed dose combination (FDC) capsule
      formulations. Six healthy male volunteers participated in a single dose, two
      treatment, two period, cross-over study. A sensitive, specific and accurate HPTLC
      method was developed, validated and employed for estimation of RIF and its major
      active metabolite, 25-Desacetylrifampicin (25-DAR) levels, in urine. Using the
      urinary excretion data various pharmacokinetic parameters: AUC(0-24), AUC(0
      infinity), cumulative amount excreted in 24 h, peak excretion rate, etc. for both
      RIF and 25-DAR were calculated and compared statistically (ANOVA, 90% confidence
      interval for ratio). Significant decrease in the bioavailability ( approximately
      32% as RIF and approximately 28% as 25-DAR) of RIF from FDC capsules was
      observed. The present bioavailability study confirms our serious doubts about the
      stability of RIF in presence of INH in acidic environment of stomach, which
      probably is the main factor responsible for the reduced bioavailability of RIF
      from RIF-INH combination formulations. This study underlines the fact that there
      is an urgent need to reconsider the formulation of the FDC product in order to
      minimize or avoid the decomposition of RIF in gastrointestinal tract.

PMID- 11576769
TI  - In vitro study of low-frequency ultrasound-enhanced transdermal transport of
      fentanyl and caffeine across human and hairless rat skin.
AB  - The effect of low-frequency sonophoresis on fentanyl and caffeine permeation
      through human and hairless rat skin was studied in vitro. Experiments were
      performed using 20 kHz ultrasound applied at either continuous or discontinuous
      mode and with an average intensity of 2.5 W/cm(2). The results showed that low
      frequency ultrasound enhanced the transdermal transport of both fentanyl and
      caffeine across human and hairless rat skin. This was explained by both
      increasing flux during sonication and shortening the lag time. Discontinuous mode
      was found to be more effective in increasing transdermal penetration of fentanyl
      while transdermal transport of caffeine was enhanced by both continuous and
      pulsed mode. Histological and electron microscopy studies showed that human and
      hairless rat skin was unaffected by ultrasound exposure. Further studies will be
      necessary to determine the relative contribution of ultrasound parameters in low
      frequency ultrasound-induced percutaneous enhancement of drug transport.

PMID- 11576770
TI  - Evaluation of in vitro percutaneous absorption of lorazepam and clonazepam from
      hydro-alcoholic gel formulations.
AB  - Clonazepam and lorazepam are two anxiolytics, antidepressant agents, having
      suitable features for transdermal delivery. The objectives of this study were to
      evaluate the in vitro percutaneous absorption of these drugs through excised
      human skin (stratum corneum and epidermis, SCE) and to determine their in vitro
      permeation behavior from a series of hydro-alcoholic gel formulations containing
      various enhancing agents. The best permeation profile was obtained for both drugs
      applying them together with Azone in combination with propylene glycol (PG):
      these enhancers were able to increase the clonazepam and lorazepam percutaneous
      fluxes at steady-state about threefold, compared to the free enhancer
      formulations (Control). To explain the mechanism of the used promoters, the
      benzodiazepine diffusion and partitioning coefficients from the gel containing
      the enhancers were calculated. The results indicated that the Azone in
      combination with PG could act by increasing the benzodiazepine diffusion
      coefficients, Transcutol increased only the SC/vehicle partition coefficients,
      limonene in combination with PG appeared to increase both partition and diffusion
      coefficients moderately, while PG did not increase both the parameters.
      Furthermore, to evaluate the potential application of tested benzodiazepine
      formulations containing Azone in combination with PG using the flux values from
      the in vitro experiments, the corresponding steady-state plasma concentrations
      (C(SS)) were calculated. The obtained calculated C(SS) values are within the
      lorazepam therapeutic range and suggest that transdermal delivery of this drug
      could be regarded as feasible.

PMID- 11576771
TI  - Effect of melting point of chiral terpenes on human stratum corneum uptake.
AB  - The effect of melting point of chiral penetration enhancers on their stratum
      corneum uptake was investigated. The pure enantiomers of a chiral compound often
      possess different melting points, and therefore dissimilar solubilities, to the
      racemate because of variations in their crystal structure. Two terpenes, menthol
      and neomenthol, saturated in propylene glycol/water, were applied to stratum
      corneum. Racemic menthol melts at approximately 33 degrees C, some 9 degrees C
      lower than the pure enantiomers, whereas racemic neomenthol melts at 26 degrees C
      higher than the study temperature, considered as the theoretical melting point of
      its enantiomers, which are both liquids. Terpene solubility increased with the
      propylene glycol content of the vehicle. The lower melting forms of both
      penetration enhancers possessed the highest solubility in every vehicle. Maximum
      stratum corneum uptake was obtained from formulations containing the lower
      melting forms of each enhancer in 60% w/w propylene glycol systems (highest
      concentration used). Compared with menthol, the larger melting point difference
      between optical forms of neomenthol produced bigger differences in their uptake.
      Thus melting point depression of menthol and neomenthol, by selection of the
      appropriate optical form, increased the amount of terpene delivered to the
      stratum corneum, in agreement with theoretical predictions.

PMID- 11576772
TI  - The effect of surfactants on the skin penetration of diazepam.
AB  - The percutaneous permeation of diazepam was investigated in rat skin after
      application of a water-propylene glycol (50:50% v/v) using a diffusion cell
      technique. The effect of various surfactants (sodium lauryl sulfate (SLS),
      cetyltrimethylammonium bromide (CTAB), benzalkonium chloride or Tween 80) with
      different concentrations on skin permeability were evaluated. Flux, K(p), lag
      time and enhancement ratios (ERs) of diazepam were measured over 10 h and
      compared with control sample (containing no surfactant). Furthermore, diazepam
      solubility in presence of surfactants was determined. The in vitro permeation
      experiments with rat skin revealed that the surfactant enhancers varied in their
      ability to enhance the flux of diazepam. Benzalkonium chloride which possessed
      the highest lipophilicity (logP=1.9) among cationic surfactants provided the
      greatest enhancement for diazepam flux (7.98-fold over control). CTAB (logP<1) at
      a concentration of 1% w/w exhibited no significant increase in flux of diazepam
      compared to control (1.16-fold over control). The results also showed that the
      highest ER was obtained in presence of 1% w/w surfactant with the exception of
      SLS and CTAB. The increase in flux at low enhancer concentrations is normally
      attributed to the ability of the surfactant molecules to penetrate the skin and
      increase its permeability. Reduction in the rate of transport of the drug present
      in enhancer systems beyond 1% w/w is attributed to the ability of the surfactant
      to form micelles and is normally observed only if interaction between micelle and
      the drug occurs. The results showed that the nature of enhancer greatly
      influences cutaneous barrier impairment.

PMID- 11576773
TI  - Physicochemical properties of microemulsion analogues of low density lipoprotein
      containing amphiphatic apoprotein B receptor sequences.
AB  - Low density lipoprotein (LDL) has been proposed as a drug targeting vector in
      cancer chemotherapy, however, research has been limited due to the necessity to
      isolate material from plasma. In this study, the physicochemical properties of
      synthetic lipid microemulsions containing an amphiphatic version of the
      apoprotein B receptor binding sequence have been examined. The effect of peptide
      sequence length, lipid anchor type and location along with microemulsion lipid
      composition were investigated via changes in particle size and zeta potential.
      Size increases were related to the amphiphatic peptides lipophilic portion and
      too a lesser extent by amino acid sequence length. Two lipophilic anchors,
      retinoic acid and cholesterol, produced large size increases whilst a single
      anchor (retinoic acid) did not affect size. The amphiphatic peptide reversed
      measured zeta potential from negative to positive values in a concentration
      dependent manner. This was related to peptide structure and could be effected by
      changes in pH, indicating that the peptide was surface located and responsive to
      the external environment. Alteration of microemulsion lipid composition also
      affected physicochemical properties but to a lesser degree than changes in the
      amphiphatic peptide. These novel systems may represent a useful synthetic
      alternative to native LDL for a variety of applications.

PMID- 11576774
TI  - Preparation and in vitro evaluation of verapamil HCl and ibuprofen containing
      carrageenan beads.
AB  - The objective of this study was to prepare and evaluate carrageenan beads as a
      controlled release system for a freely water soluble drug verapamil hydrochloride
      and a slightly water soluble drug ibuprofen. Beads were prepared by ionotropic
      gelation method. The influence of formulation factors (drug content, polymer
      concentration, counterion type and concentration, outer phase volume) on the
      particle size, encapsulation efficiency and in vitro release characteristics of
      beads was investigated. The encapsulation efficiency of veraparnil HCl in the
      beads (34.8-71.1%) was higher than that of ibuprofen (23.6-58%). While about 30%
      of ibuprofen was released at 6 h, about 70% of verapamil HCl was released in 5 h
      from the carrageenan beads prepared.

PMID- 11576775
TI  - Macromolecular prodrugs. IX. Synthesis of polymer-fenoprofen conjugates.
AB  - Synthesis of several polymer-fenoprofen conjugates is described. Fenoprofen was
      first chemically modified into benzotriazolide 2 and amino acid amide
      derivatives: glycine fenoprofenamide (3a) and beta-alanine fenoprofenamide (3b)
      and their benzotriazolides 6a and 6b. Compounds 2 and 6 readily reacted with
      polyhydroxy aspartamide-type polymers, i.e. poly[alpha,beta-(N-2-hydroxyethyl-DL
      aspartamide)] (PHEA) and poly[alpha,beta-(N-3-hydroxypropyl-DL-aspartamide)]
      (PHPA) forming conjugates 5, 8a,b and 9a,b, respectively. Conjugate 11 was
      obtained by partial aminolysis of poly-DL-(2,5-dioxo-1,3-pyrrolidinediyl) (PSI)
      with 2-aminoethyl fenoprofenamide (3c), followed by total aminolysis with 2
      hydroxyethylamine. The synthesised polymer-drug conjugates differed in type of
      covalent bounding, type and/or length of spacer and drug-loading.

PMID- 11576776
TI  - Micro-scale measurement of the mechanical properties of compressed pharmaceutical
      powders. 2: The dynamic moduli of microcrystalline cellulose.
AB  - The use of two 'micro-scale' dynamic mechanical testing techniques for
      determining the viscoelastic properties of very small microcrystalline cellulose
      compacts ( approximately 20 mg) is reported. The first method is a simple tensile
      'stretching' test, and the second is a dynamic version of the three-point beam
      bending technique. For both approaches the storage (elastic) and loss (viscous)
      moduli could be readily determined for compacts of a wide range of porosities.
      The experimentally determined storage moduli were consistently one order of
      magnitude greater than the corresponding loss moduli indicating a dominating
      elastic response for the microcrystalline cellulose compacts. The moduli
      determined using the oscillating three-point beam-bending technique were slightly
      lower than expected and this was attributed to sample anisotropy and imperfect
      sample alignment/friction during testing. The moduli obtained using the simple
      dynamic tension tests were practically identical to complex moduli values
      reported for much larger specimens, and it appears that this technique is well
      suited to measuring the dynamic mechanical properties of very small
      pharmaceutical powder compacts.

PMID- 11576777
TI  - Heparin penetration into and permeation through human skin from aqueous and
      liposomal formulations in vitro.
AB  - The transport of unfractionated (UH) and low molecular weight Heparin (LMWH) in
      human skin was investigated in vitro using heat separated epidermal membrane and
      dermis and the effect of liposomal formulations with Phospholipon(R) 80 (PL80)
      and Sphingomyelin (SM) was assessed. The distribution of Heparin within skin
      tissue was studied by the tape stripping method. Heparin concentrations were
      measured with a biological assay. Transepidermal water loss was determined to
      characterize barrier properties of skin. No consistent permeation of Heparin
      through epidermal membrane was detected. Penetration into the epidermal membrane
      was for LMWH significantly greater than for UH. Accumulation of UH was largely
      restricted to the outermost layers of the stratum corneum while LMWH penetrated
      into deeper epidermal layers. UH penetration into epidermis was detected for the
      PL80 liposomal formulation only. The extent of LMWH penetration was independent
      of the formulation, LMWH, however, showed a trend to accumulate in deeper
      epidermal layers for the PL80 compared to the aqueous formulation. Thus,
      molecular weight and liposomal formulations influenced the penetration pattern of
      Heparin in the epidermis. It can not be concluded whether the concentration of
      LMWH achieved at the blood capillaries is sufficient to exert a pharmacological
      effect. UH permeated readily through dermis irrespectively of formulation and its
      accumulation in the dermis was significantly enhanced and its lag time of
      permeation increased in the presence of SM liposomes.

PMID- 11576778
TI  - Transdermal delivery of ketoprofen using microemulsions.
AB  - A transdermal preparation containing ketoprofen was developed using O/W
      microemulsion system. Of the oils tested, oleic acid was chosen as the oil phase
      of the microemulsion, as it showed a good solubilizing capacity and excellent
      skin permeation rate of the drug. Pseudoternary phase diagrams were constructed
      to obtain the concentration range of oil, surfactant and cosurfactant for
      microemulsion formation, and the effect of these additives on skin permeation of
      ketoprofen was evaluated with excised rat skins. The optimum formulation of the
      microemulsion consisted of 3% ketoprofen, 6% oleic acid, 30% Labrasol/Cremophor
      RH 40 (1:1) and water. Terpenes were added to the microemulsion at the level of
      5% and their effect on the skin permeation of ketoprofen from the microemulsion
      was evaluated. Of the four terpenes used, only limonene resulted in a powerful
      enhancing activity (3-fold increase over control).

PMID- 11576779
TI  - Modulation of P-glycoprotein activity in Calu-3 cells using steroids and beta
      ligands.
AB  - The purpose of this work was to investigate if P-glycoprotein (Pgp) efflux pump
      activity could be inhibited in the sub-bronchial epithelial cell line, Calu-3, by
      glucocorticosteroids and beta-ligands. The Pgp modulation efficiency of each
      compound was determined by its ability to increase the accumulation of the Pgp
      substrate rhodamine 123 (Rh123) accumulation in these cells. Pgp inhibition was
      observed at > or =100 microM steroids and beta-ligand. The modulation
      effectiveness of the beta-ligands increased with increasing hydrophobicity
      (logP(octanol/aqueous)) whereas an obvious correlation was not obtained with the
      complete set of steroids tested. Steroidal Pgp substrates did not affect Rh123
      accumulation (e.g. aldosterone, dexamethasone, 11beta,17alpha,21-OH
      progesterone). In contrast, two hydrophobic non-Pgp steroidal substrates
      (testosterone and progesterone) displayed different effects on Rh123
      accumulation, with progesterone being the more potent modulator. The most
      hydrophobic beta-ligand, propranolol, a known Pgp substrate, gave the largest
      increase in Rh123 accumulation in this therapeutic class. The beta-ligand
      modulation efficiency could also be correlated to Pgp structural recognition
      elements such as hydrogen bonding potential, the presence of a basic nitrogen and
      planar aromatic ring. No effect on Rh123 accumulation was observed with the
      formulation additives tested (ethanol, glycerol and palmitoyl carnitine) at
      concentrations previously reported to be non-toxic to Calu-3 cells.

PMID- 11576780
TI  - Optimized conditions of bio-mimetic artificial membrane permeation assay.
AB  - Effects of pH and co-solvents on the bio-mimetic artificial membrane permeation
      assay were investigated to determine the optimal conditions for the prediction of
      oral absorption. The permeability (P(am)) of 33 structurally diverse drugs to the
      PC/PE/PS/PI/CHO/1,7-octadiene membrane system (bio-mimetic lipid (BML) membrane)
      was measured at pH 5.5, 6.5, and 7.4. The pH dependence of P(am) was in
      accordance with the pH partition theory. The better prediction of oral absorption
      (fraction of a dose absorbed) was shown under the pH 5.5 condition (r=0.866,
      n=25) and/or pH 6.5 (r=0.865, n=28), rather than pH 7.4 (r=0.767, n=24). Then,
      the appropriate conditions for determining the permeability of poorly soluble
      compounds were examined. Dimethysulfoxide (DMSO), ethanol (EtOH) and
      polyoxyethyleneglycol 400 (PEG 400) were added up to 30% to the transport medium
      as solubilizers. DMSO, EtOH and PEG 400 decreased P(am) of hydrocortisone and
      propranolol. For example, DMSO (30%) decreased P(am) of hydrocortisone by 60% and
      by 70% in the case of propranolol. DMSO and PEG 400 also decreased P(am) of
      ketoprofen. In contrast, EtOH produced an opposite effect on permeability, i.e.
      an increased P(am) of ketoprofen. Therefore, the high concentration of these co
      solvents could lead to the under- or overestimation of drug permeability.

PMID- 11576781
TI  - Factors influencing drug release from stearic acid based compacts.
AB  - Fatty acids are potentially suitable carriers for use in the design of drug
      delivery systems, being biocompatible, biodegradable inexpensive and of low
      toxicity. The release of the model compound benzoic acid from fatty acid compacts
      of stearic acid was evaluated using the USP Apparatus 2 dissolution assembly in
      phosphate buffer pH 7.4. Matrix controlled drug release was expected. Release
      profiles were approximated by square root of time kinetics. Release rate was
      independent of stirring speed in the rpm range 50-150, however, at 200 rpm a
      significant increase in release rate was observed particularly at later times,
      the amount released versus square root of time plots becoming non-linear. Release
      was independent of compression pressure in the range 1-7 tons. The particle size
      of the benzoic acid and stearic acid used had a significant influence on release.
      The use of particles in the range 250-500 microm gave release rate constants (k,
      g/cm(2) per min(0.5)) approximately 1.5 greater than those of smaller particle
      size (63-125 microm). The formation factor (F) tended to increase exponentially
      with drug loading, the increase being steeper for compacts prepared from the
      larger particle sizes. At 80% drug loading for large sized systems the matrix
      appeared to offer little resistance to drug release and F approached one.

PMID- 11576782
TI  - Determination of partial solubility parameters of five benzodiazepines in
      individual solvents.
AB  - Three and four component partial solubility parameters for diazepam, lorazepam,
      oxazepam, prazepam and temazepam were determined using the extended and expanded
      Hansen regression models. A comparison was made also with solubility parameters
      calculated by the group contribution method proposed by Van Krevelen. Although a
      limited number of solvents was used, the results from the present study indicate
      that the partial solubility parameters obtained from the experimental regression
      models clearly reflect the structural differences in these five structurally
      related molecules. High R(2)-values were observed in the regression models (0.932
      < or =R(2)< or =0.984), except for lorazepam (0.606 < or =R(2)< or =0.825). This
      was attributed to difficulties in obtaining reliable values of the temperature
      and heat of fusion due to thermal decomposition of this compound. Introduction of
      the Flory-Huggins size correction parameter did not improve the R(2)- and F
      values in any of the regression models used.

PMID- 11576783
TI  - Evaluation of the mechanical destructive force in the stomach of dog.
AB  - Orally administered dosage forms receive a destructive force in the
      gastrointestinal (GI) tract due to peristalsis. In this study, the destructive
      force was measured with a 'destructive force-dependent release system' (DDRS).
      DDRS is a press-coated tablet with an extremely brittle outer layer composed of
      highly hydrophobic Teflon(R) powder, which is molded with a weak compression
      force. Teflon(R) powder forms a porous but water-impermeable layer around the
      core tablet. A marker drug contained in the core tablet is released only when the
      tablet receives a force larger than its pre-determined crushing strength. A
      comparison of the physiological conditions in the GI tract of dogs with those of
      humans, including the destructive force against tablets in the stomach, helps us
      to understand their difference in bioavailability of oral dosage forms. With
      DDRS, it is possible to evaluate the destructive force of both human and dog
      stomach using the same method. Therefore, the destructive force data from human
      and dog can be directly compared. The destructive force in the dog stomach was
      evaluated to be 3.2 N, which was considerably stronger than that of humans.

PMID- 11576784
TI  - Resistivities of placebo and active Diskus inhalers compared.
AB  - OBJECTIVE: Verbal instruction and demonstration of inhalation technique are
      essential to enhance the effectiveness of inhalation therapy. Placebo devices are
      commonly used to instruct patients. It is not obvious that patients, who inhale
      with an adequate flow through an empty placebo Diskus, would also be able to do
      so with active inhalers containing a strip with powder. The presence of powder
      may result in a change in resistivity. We compared the resistivities of a placebo
      Diskus being empty; a powder filled Diskus inhaler and a Diskus inhaler with an
      empty blister. METHODS: A Diskus inhaler was placed in a box, which enabled
      measurement of pressure drop and flow rates. Ten placebo and ten Ventolin Diskus
      inhalers were measured. Twelve pressure- and flow-profiles were recorded through
      each device. After each simulated inhalation through a powder filled blister, a
      second inhalation was performed through the empty blister. The resistivity was
      calculated by pressure-flow equation. RESULTS: The resistivity of the empty
      placebo Diskus inhaler was slightly but significantly higher than both blister
      filled inhalers, with or without powder (0.0215 vs. 0.0211 and 0.0211 (kPa)(0.5)
      (l min(-1))(-1)) (P<0.001). CONCLUSION: Patients who are capable of generating
      sufficient flow through a placebo Diskus will surely be capable of generating
      equivalent flows through a Diskus inhaler containing a strip with active drug
      substance.

PMID- 11576785
TI  - PCR and sequencing of independent genetic targets for the diagnosis of culture
      negative bacterial endocarditis.
AB  - Molecular methods utilizing broad-range primers for 16S rDNA PCR and sequencing
      have been widely evaluated for their utility in culture negative diagnostic
      bacteriology. Difficulties in determining the incidence of false positive PCR
      results, especially in the absence of an equally sensitive confirmatory method
      however, have prevented wide clinical use of this sensitive technology. Here we
      report two cases of culture-negative endocarditis, in which PCR using 16S rDNA
      broad-range primers generated sequences specific for Bartonella spp. and
      Streptococcus oralis, respectively. To confirm these results, a second species-
      or genus-specific molecular target was chosen for each organism and detected in
      the split samples sequencially. Thus, molecular detection of a second species
      specific target can be used to confirm PCR results generated from 16S rDNA broad
      range primers and to control for potential false positive results due to
      environmental and amplicon carry-over contamination during specimen processing
      and testing in the laboratory.

PMID- 11576786
TI  - EPEC, EAEC and STEC in stool specimens: prevalence and molecular epidemiology of
      isolates.
AB  - Stool specimens of Finns (n = 695) with (n = 603) and without (n = 92) diarrhea
      were studied for enteropathogenic (EPEC), enteroaggregative (EAEC) and Shiga
      toxin-producing (STEC) Escherichia coli by PCR. The specific isolates were
      subsequently investigated for their O:H serotypes and were genotyped by pulsed
      field gel electrophoresis (PFGE). A subset (n = 506) of the diarrheal and all non
      diarrheal specimens were also searched for conventional enteric bacterial
      pathogens by standard methods. Diarrheagenic E. coli were found in 5.5% and other
      enteric pathogens in 6.7% of the patients with and in 2.2% and 1.1% of the
      subjects without diarrhea, respectively. Campylobacter (3.8%), EPEC (3.2%) and
      Salmonella (2.0%) were the most common findings, and were detected in diarrheal
      patients only. STEC were associated with bloody diarrhea (8/9 isolates), whereas
      EAEC were equally common (1%) in diarrheal and non-diarrheal subjects. Great
      genomial heterogeneity was seen among diarrheagenic E. coli, and only one EPEC
      isolate belonged to the "classic" EPEC serogroup (O55).

PMID- 11576787
TI  - Evaluation of an automated system for the identification and antimicrobial
      susceptibility testing of enterococci.
AB  - The performance of a new version of an automated system panel, the Positive Combo
      Panel Type 11 of MicroScan WalkAway 96 (WA96; Dade Behring) was evaluated and
      compared to that of reference methods for the identification and for
      antimicrobial susceptibility testing of the different enterococcal species. A
      total of 376 enterococcal isolates were tested. The MicroScan WA96 correctly
      identified 99.6% (266/267), 78.3% (18/23) and 68.6% (59/86) of Enterococcus
      faecalis, Enterococcus faecium and species other than E. faecalis and E. faecium,
      respectively. Although low probability of accurate identification was obtained
      for 37 (9.8%) strains, the system indicated that supplementary tests were
      necessary for precise identification of 8 (9.3%) among the 86 strains included in
      the non-faecalis/non-faecium group and of 3 (13.0%) among the E. faecium
      isolates. In comparison to the agar screening method, the percentage of agreement
      for detection of resistance markers by the automated system was 90.2% (37/41) for
      ampicillin, 90.6% (48/53) for high-level resistance to streptomycin (HLRS), 96.4%
      (80/83) for high-level resistance to gentamicin (HLRG), and 100% (14/14) for
      vancomycin. The results indicate that the MicroScan WA96 performed well for the
      identification of E. faecalis and typical E. faecium isolates, and for the
      detection of resistance to vancomycin and HLRG. However, the system still needs
      further improvement in order to provide reliable results for the characterization
      of the other enterococcal species, including atypical variants of E. faecium.

PMID- 11576788
TI  - Amplification of the DNA polymerase I gene of Treponema pallidum from whole blood
      of persons with syphilis.
AB  - Previous reports suggest that Treponema pallidum bacteremia occurs in persons
      with syphilis exposure ('incubating syphilis') and in persons with primary or
      secondary syphilis. During a recent syphilis outbreak, whole blood samples from
      32 persons with suspected syphilis or syphilis exposure were screened using
      polymerase chain reaction (PCR) to amplify the DNA polymerase I gene (polA) of T.
      pallidum. Of the 32 samples, polA was amplified from 13 (41%). Of these 13, three
      were determined to have incubating syphilis; two had primary or secondary
      syphilis and eight had latent syphilis. This study demonstrates that
      spirochetemia can occur throughout the course of T. pallidum infection.

PMID- 11576789
TI  - Comparative anti-staphylococcal effects of gemifloxacin and trovafloxacin in an
      in vitro dynamic model in terms of AUC/MIC and dose relationships.
AB  - To compare the antimicrobial effects of gemifloxacin and trovafloxacin on
      Staphylococcus aureus, their pharmacodynamics were studied in an in vitro dynamic
      model. A series of pharmacokinetic profiles of gemifloxacin and trovafloxacin
      with half-lives of 7.4 and 9.2 h, respectively, were simulated in vitro over an
      eightfold range of area under the curve (AUC)-to-MIC ratio, from 58 to 466 h. The
      relationships observed between the intensity of antimicrobial effect (I(E)) and
      log AUC/MIC were linear, species- and strain-independent and were distinct (not
      superimposed) for both gemifloxacin and trovafloxacin (r(2) = 0.99 in both
      cases). At AUC/MICs > 100 h, trovafloxacin had greater effects than gemifloxacin.
      For example, at an AUC/MIC of 250 h, the antimicrobial effect of trovafloxacin
      was 17% higher than gemifloxacin. However, due to its higher intrinsic activity,
      gemifloxacin may be as efficient as trovafloxacin at their clinical doses (320
      and 200 mg, respectively): the I(E)s on a hypothetical strain of S. aureus with
      gemifloxacin's and trovafloxacin's MICs corresponding to the MIC(50)s were
      similar-290 and 310 (log CFU/mL)x h, respectively. This analysis suggests that
      both AUC/MIC and dose relationships of the antimicrobial effect are needed for
      comprehensive comparisons of fluoroquinolone pharmacodynamics.

PMID- 11576790
TI  - In vitro antimicrobial activity of GAR-936 tested against antibiotic-resistant
      gram-positive blood stream infection isolates and strains producing extended
      spectrum beta-lactamases.
AB  - GAR-936, a new, semisynthetic glycylcycline, has shown good antibacterial
      activity against a wide range of clinically important Gram-positive and -negative
      aerobic bacteria including Streptococcus pneumoniae, Hemophilus influenzae,
      Moraxella catarrhalis, Neisseria gonorrhoeae, most Enterobacteriaceae,
      Staphylococcus aureus and Enterococcus spp. The purpose of this study was to
      determine the activity of GAR-936 against a range of Gram-positive and -negative
      bloodstream isolates including many strains producing extended-spectrum beta
      lactamases (ESBLs). Six hundred four bloodstream isolates of Gram-positive cocci
      collected as part of the SENTRY surveillance program were selected for their
      geographic diversity. GAR-936 was also tested against an additional 176 Gram
      negative cocci isolates (Klebsiella pneumoniae, 98 strains; Escherichia coli, 78
      strains), 96 of which were ESBL-producers. Broth microdilution testing was used
      to determine the susceptibility of the selected organisms and a range of
      comparator antimicrobial agents whose choice was based on their activities
      against the selected pathogens and included a mix of both newer and older agents.
      Presence of an ESBL-producing strain was confirmed using the clavulanate test.
      GAR-936 demonstrated impressive activity against all 604 strains of Gram-positive
      cocci, with an MIC range of <or=0.015-1 microg/mL, and MIC(90)s ranging from
      <or=0.05 microg/mL for S. pneumoniae to 0.25 for S. aureus and coagulase-negative
      staphylococci. MICs against the 176 Gram-negative isolates were higher (range
      0.06-4 microg/mL), with MIC(90)s of 0.25-1 microg/mL. The activity of GAR-936 was
      relatively unaffected by the presence of ESBLs. The activity of GAR-936 was
      particularly impressive against Gram-positive cocci when compared against the
      test results for vancomycin and the newer antimicrobial agents, linezolid and
      quinupristin/dalfopristin. The MIC(90)s for GAR-936 were significantly lower than
      the comparator agents for all species tested with particularly impressive results
      against S. pneumoniae and enterococci.

PMID- 11576791
TI  - Evaluation of E test, disk diffusion and broth microdilution to establish
      tentative quality control limits and review susceptibility breakpoints for two
      aerobic actinomycetes.
AB  - A single laboratory study was carried out to compare E Test with broth
      microdilution and disk diffusion to establish tentative quality control ranges
      for Nocardia asteroides ATCC 19247 and Rhodococcus equi ATCC 6939 against a panel
      of eight antimicrobial agents. Reproducibility testing was performed on 12
      consecutive days to establish tentative quality control ranges. A total of 36
      clinical strains of the Nocardia asteroides complex and 5 Rhodococcus strains
      were used in the study. Both candidate control strains and clinical strains grew
      well on cation-adjusted Mueller-Hinton agar. Adequate growth occurred at 48 to 72
      h for the Nocardia isolates and 24 to 48 h for Rhodococcus. A standardized
      primary inoculum of 5 x 10(4) CFU/mL was used for performance of E Test and disk
      diffusion for the Nocardia isolates. Tentative population-based error rates were
      calculated using current breakpoints for Enterobacteriaceae for E Test compared
      with disk diffusion for the 36 clinical strains of Nocardia species. Significant
      very major error rates were observed for imipenem (22%) and minor error rates
      varied from 2.7% to 50%. These methods require more extensive validation before
      definitive breakpoint criteria can be established.

PMID- 11576792
TI  - Comparative in vitro activity of gemifloxacin against gram-positive and gram
      negative clinical isolates in Argentina.
AB  - The in vitro activity of gemifloxacin against 1,000 clinical isolates of 147
      Streptococcus pneumoniae (115, penicilin susceptible; 26, intermediate penicillin
      resistant and 6, penicillin-resistant), 127 Hemophilus influenzae (109, beta
      lactamasa non-producer; 18, beta lactamase producers), 95 Streptococcus pyogenes
      (6, azytromycin-resistant), 84 Moraxella catarrhalis (79, beta lactamase
      producers), 110 Staphilococcus aureus (89, methicillin-susceptible; 21,
      methicilin-resistant), 98 Eenterococcus faecalis and 339 Enterobacteriacea,
      (recovered from patients with respiratory tract infection; skin and soft tissue
      infection and urinary tract infection), was compared with the activities of four
      fluorquinolones and five other antimicrobial agents. Of the quinolones tested,
      gemifloxacin was the most potent against Streptococcus pneumoniae, including
      penicillin intermediate and resistant strains. Mic(90) values obtained for
      gemifloxacin, ciprofloxacin, ofloxacin, levofloxacin and trvafloxacin were 0.03,
      2, 2, 1 and 0.25 mg/L respectively. Gemifloxacin was 16 fold more potent than
      ciprofloxacin against methicillin-susceptible Staphylococcus aureus and 32 fold
      more potent than ciprofloxacin against Streptococcus pyogenes. When tested
      against Hemophilus influenzae, Moraxella catarrhalis and Enterobacteriaceae, all
      the quinolones showed similar activity. Our results demonstrate that gemifloxacin
      has similar activity than the other quinolones tested against Gram-negative
      organisms and is considerably more potent against Gram-positive organisms.

PMID- 11576793
TI  - Fluoroquinolone susceptibility, resistance, and pharmacodynamics versus clinical
      isolates of Streptococcus pneumoniae from Indiana.
AB  - The in vitro activity and pharmacodynamics (AUC(0-24)/MIC) of levofloxacin,
      gatifloxacin, moxifloxacin, and gemifloxacin were evaluated against 307 clinical
      isolates of Streptococcus pneumoniae from Indianapolis, Indiana. Organisms were
      collected between January 1999 and April 2000, and MICs were determined by broth
      microdilution. Serum concentration-time profiles were simulated for the following
      oral regimens administered once daily: levofloxacin 500 mg and 750 mg;
      gatifloxacin 400 mg; moxifloxacin 400 mg; gemifloxacin 320 mg. Free 24 h area
      under the serum concentration-time curves (AUC(0-24)) were calculated, and the
      average AUC(0-24)/MIC was calculated for each regimen. Differences in AUC(0
      24)/MIC among agents were determined by analysis of variance (Scheffe post-hoc
      test, p < 0.05). Overall, gemifloxacin was the most potent agent tested. Five
      (1.7%), 4 (1.3%), and 2 (0.7%) isolates were resistant to levofloxacin,
      gatifloxacin, and moxifloxacin, respectively. None of the isolates was resistant
      to gemifloxacin. Gemifloxacin AUC(0-24)/MIC was significantly greater than all
      other regimens (p < 0.0001), with the exception of moxifloxacin. However, the
      percent of isolates for which an AUC(0-24)/MIC >or= 30-50 can be achieved is
      similar for gemifloxacin, moxifloxacin, gatifloxacin, and levofloxacin 750 mg.
      Large comparative studies are needed to determine if the differences in AUC(0
      24)/MIC among fluoroquinolones are clinically significant.

PMID- 11576794
TI  - Enzymatic characterization of TEM-63, a TEM-type extended spectrum beta-lactamase
      expressed in three different genera of Enterobacteriaceae from South Africa.
AB  - The extended-spectrum beta-lactamase, TEM-63, was identified in three separate
      genera of South African isolates: Proteus mirabilis, Klebsiella pneumoniae, and
      Escherichia coli. This paper describes identification of the gene in these
      isolates and compares relative rates of hyrolysis between TEM-63 and other known
      ceftazidimases.

PMID- 11576795
TI  - Oxacillin susceptibility testing of Staphylococcus saprophyticus using disk
      diffusion, agar dilution, broth microdilution, and the Vitek GPS-105 card.
AB  - Eighty-three mecA negative isolates of S. saprophyticus had oxacillin zone
      diameters <or= 15 mm or MICs ranging from <or= 0.25-1.0 microg/ml when tested by
      either agar dilution, broth microdilution, or the Vitek GPS-105 card. Greater
      than 90% of these isolates would be considered resistant using NCCLS M7-A5, M100
      S10 criteria. These results suggest that the current NCCLS MIC and zone diameter
      breakpoints for oxacillin resistance in coagulase-negative Staphylococci are not
      appropriate for S. saprophyticus as they do not correlate with the presence of
      the mecA gene.

PMID- 11576796
TI  - Effect of extended pre-incubation with chlamydia pneumoniae and extended
      incubation with antimicrobial on the minimum inhibitory concentrations (MICs) of
      five antimicrobials.
AB  - There is no single standard methodology for in vitro susceptibility testing for
      Chlamydia pneumoniae, but many investigators pre-incubate this organism with the
      cell monolayer for 1 h prior to adding antimicrobial and incubating for 72 h. The
      aim of this study was to determine the effect of extended C. pneumoniae pre
      incubation, and extended incubation in the presence of antimicrobial, on the MICs
      of 5 antimicrobials. MICs were determined for 5 ATCC strains of C. pneumoniae by
      employing similar methods as those previously described in the literature. MICs
      were then determined following 1, 4, 6, 20 and 24 h C. pneumoniae pre-incubation.
      Finally, MICs were determined following 1 and 24 h C. pneumoniae pre-incubation,
      and 48 and 72 h incubation with antimicrobial and organism. Extending the
      incubation time in the presence of antimicrobial from 48 to 72 h had little or no
      effect on MICs. Similarly, pre-incubation periods of less than 20 h had little
      effect on MICs, but MICs increased significantly with 20 and 24 h pre-incubation.

PMID- 11576797
TI  - Confronting the prospect of dying. reports of terminally ill patients.
AB  - To identify dominant themes characterizing patients' perspectives on death during
      their last months of life, an ethnographic technique of interviewing and an
      inductive qualitative approach to analysis were employed. Serial, in-depth, semi
      structured interviews were conducted with 30 patients (mean = 4.2
      interviews/patient) followed as close to the time of death as possible. The
      interviews were audiotaped, transcribed, and subjected to independent analysis by
      both authors using standard qualitative techniques. Patients were referred to the
      study by Beth Israel Medical Center clinicians if they had a diagnosis of a life
      threatening condition of which they were aware; were likely to die within one
      year according to their physician; had experienced symptoms of the illness; were
      sufficiently alert to discuss the topics addressed in the study; conversed easily
      in English; and consented to participate. Outlooks on dying were thoroughly
      grounded in patients' frames of reference for giving meaning and consistency to
      other major events in their lives. Seven motifs characterizing these perspectives
      on death were distilled: struggle (living and dying are difficult), dissonance
      (dying is not living), endurance (triumph of inner strength), coping (finding a
      new balance), incorporation (belief system accommodates death), quest (seeking
      meaning in death), and volatile (unresolved and unresigned). Patients
      demonstrated a striking capacity for coherence, integrating their responses to
      dying with broader motifs in their life stories. Health care providers would be
      well advised to become aware of such motifs so as to better understand patient
      preferences for care and responses to treatment recommendations.

PMID- 11576798
TI  - Xerostomia in patients with advanced cancer.
AB  - The aim of the study was to investigate the features of xerostomia in patients
      with advanced cancer. The protocol involved completion of the Memorial Symptom
      Assessment Scale, and measurement of the unstimulated whole salivary flow rate
      (UWSFR) and the stimulated whole salivary flow rate (SWSFR). One hundred twenty
      patients participated in the study. Xerostomia was the fourth most common symptom
      (78% of patients). It was associated with a poor performance status (P = 0.01).
      The usual cause of xerostomia was drug treatment. There was an association with
      the total number of drugs prescribed (P = 0.009): the median number of xerostomic
      drugs prescribed was 4. Xerostomia was ranked the third most distressing symptom.
      Its severity was correlated with the severity of oral discomfort, dysgeusia,
      dysmasesia, dysphagia, dysphonia, and anorexia. The UWSFR was a relatively
      sensitive, but nonspecific, investigation. In contrast, the SWSFR was a
      relatively specific, but insensitive, investigation.

PMID- 11576799
TI  - The impact of delirium on the circadian distribution of breakthrough analgesia in
      advanced cancer patients.
AB  - Most cancer patients will experience pain requiring opioid therapy during their
      illness. Standard opioid therapy includes fixed scheduled doses and so-called
      "rescue" doses for breakthrough pain. Circadian rhythms seem to influence the
      expression of pain and the responsiveness to analgesic medication. Delirium is a
      common complication in advanced cancer patients and it also may modify the
      expression of pain and the use of analgesic medication. We reviewed the circadian
      distribution of breakthrough analgesia (BTA) doses in 104 advanced cancer
      patients who were part of a prospective study of the occurrence of delirium. We
      found that the circadian distribution of BTA is significantly different from a
      random distribution in the case of patients with and without delirium. Patients
      without delirium tended to use more BTA (P < 0.001) in the morning, whereas
      patients with delirium tended to use more BTA in the evening and at night (P =
      0.02). We conclude that delirium is associated with changes in the circadian
      distribution of BTA, which is possibly related to reversal of the normal
      circadian rhythm.

PMID- 11576800
TI  - "Burst" ketamine for refractory cancer pain: an open-label audit of 39 patients.
AB  - The results of a novel approach to the use of ketamine in refractory cancer pain
      are reported. In this prospective, multicenter, unblinded, open-label audit, 39
      patients (with a total of 43 pains) received a short duration (3 to 5 days)
      ketamine infusion. The initial dose of 100 mg/24 hr was escalated if required to
      300 mg/24 hr and then to a maximum dose of 500 mg/24hr. The overall response rate
      was 29/43 (67%). Analysis of results according to pain mechanisms showed that
      15/17 somatic and 14/23 neuropathic pains responded. In 5 patients who appeared
      to respond, it is possible that another concurrent intervention may have
      contributed in whole or part for the pain relief observed. After cessation of
      ketamine, 24/29 maintained good pain control, with a maximum documented duration
      of eight weeks. However, 5 of the initial 29 responders experienced a recurrence
      of pain within 24 hours, and ketamine was recommenced. Of these, 2 underwent
      another intervention for pain control while 3 continued on ketamine until their
      deaths between two and four weeks later. Twelve patients reported adverse
      psychomimetic effects, with the incidence rising with increasing dose. Four of
      these were non-responders and the ketamine was stopped. Eight were responders,
      and in 3 the adverse effects were rendered acceptable with dose reduction; the
      other 5 rejected a dose reduction. The results reported suggest the need for
      further investigation of the place of ketamine in cancer pain management.

PMID- 11576801
TI  - The role of patients' expectations in the development of anticipatory nausea
      related to chemotherapy for cancer.
AB  - Although anticipatory nausea (AN), which is reported by one-third of patients
      receiving chemotherapy for cancer, is thought to develop primarily by classical
      conditioning, response expectancies may also be important. The role of patients'
      expectations of nausea in the development of AN was examined in 63 female cancer
      patients receiving their first course of chemotherapy. Twenty women (32%)
      expected to experience nausea and twelve (19%) reported AN before the third
      cycle. Pretreatment expectations predicted AN at cycle three (Spearman's r =
      0.41, P = 0.001). AN developed in 40% of patients who expected nausea, 13% of
      those who were uncertain whether they would develop it, and no patients who did
      not expect nausea. Logistic regression indicated that expecting nausea was the
      strongest predictor (chi(2) =13.15; P < 0.001). Results support a role for
      cognitive factors in the development of chemotherapy side effects and suggest
      testing psychologic interventions to modify patients' expectations.

PMID- 11576802
TI  - Parents as distraction coaches during i.v. insertion: a randomized study.
AB  - This study investigated the effectiveness of a brief Distraction Education
      intervention for parents prior to their preschool children's medical procedures.
      Forty-four preschool children with chronic non-life-threatening conditions were
      having intravenous catheters (IVs) placed for medical tests. Parent-child dyads
      were randomized into two groups. The experimental group received Distraction
      Education prior to IV insertion; the control group received standard care. Data
      were analyzed for two phases of the IV procedure. Phase 1 was the preparation for
      needle insertion; Phase 2 began with needle insertion. Experimental group parents
      used significantly more distraction than did control group parents during both
      phases (P < 0.001). There were no group differences for child behavioral distress
      or self-report of pain. There was a trend toward a group by phase interaction for
      behavioral distress (P = 0.07); more experimental group children showed decreased
      behavioral distress over time (from phase 1 to phase 2) than did control group
      children (P = 0.02).

PMID- 11576803
TI  - Long-term intrathecal infusion of drug combinations for chronic back and leg
      pain.
AB  - Continuous intrathecal infusion of analgesic drugs by implantable pumps is
      recognized as an established treatment option for patients with chronic pain
      resistant to oral or parenteral medication. Polyanalgesia, the simultaneous use
      of more than one intrathecal analgesic drug, is practiced relatively often, but
      there are only a few published clinical studies on intrathecal polyanalgesia for
      chronic nonmalignant pain. This pilot study represents a long-term evaluation of
      a treatment regimen consisting of intrathecal morphine admixed with bupivacaine,
      clonidine, or midazolam in patients with chronic nonmalignant back and leg pain
      due to degenerative lumbar spinal disease. Twenty-six adult patients have been
      treated by intrathecal programmable pump-controlled infusion of analgesic drugs
      and followed for up to 3.5 years (27 +/- 11 months). Combination of morphine with
      a second drug was used in 10 cases, morphine with 2 additional drugs in 12 cases,
      and morphine with 3 additional drugs in 4 cases. Mean daily doses at 24 months
      after pump implantation were 6.2 +/- 2.8 mg for morphine, 2.5 +/- 1.5 mg for
      bupivacaine, 0.06 +/- 0.03 mg for clonidine, and 0.8 +/- 0.4 mg for midazolam.
      Nineteen patients reported excellent or good long-term treatment results, 6
      patients had sufficient results, and only 1 patient complained of poor
      therapeutic efficacy. No long-term clinical side effects of intrathecal
      polyanalgesia were noted. Mean morphine dose had to be increased from 1.2 mg at
      baseline to 5.1 mg at 24 months due to tolerance development and disease
      progression. This experience suggests that intrathecal polyanalgesia employing
      morphine combined with additional nonopioid drugs can have a favorable analgesic
      efficacy in patients with complex chronic pain of spinal origin, and lacks major
      drug-related complications.

PMID- 11576804
TI  - Establishing a cancer pain clinic in a developing country: effect of a
      collaborative link project with a UK cancer pain center.
AB  - This paper describes a project for the establishment of a cancer pain clinic in a
      developing country. The project was conducted according to guidelines from the
      World Health Organization and utilized a link with an existing cancer pain clinic
      in the UK. The principal methods used for establishing the new pain clinic
      included: an assessment of barriers to effective cancer pain control, teaching
      programs for nurses and trainee doctors, educational links with a UK cancer pain
      clinic, and analgesic guidelines and introduction of a pain assessment tool. As a
      result of these interventions, a new cancer pain clinic was founded. The methods
      used serve as one possible model for establishing cancer pain treatment
      facilities in developing countries.

PMID- 11576805
TI  - Spinal manipulation: a systematic review of sham-controlled, double-blind,
      randomized clinical trials.
AB  - For many years, spinal manipulation has been a popular form of treatment. Yet the
      debate about its clinical efficacy continues. The research question remains: Does
      spinal manipulation convey more than a placebo effect? To summarize the evidence
      from sham-controlled clinical trials of spinal manipulation as a treatment of
      various conditions, and to assess the methodological quality of these studies, a
      comprehensive search strategy was designed to locate all sham-controlled, double
      blind, randomized trials of spinal manipulation as a treatment of any medical
      condition. Data were extracted from these trials and validated by two independent
      reviewers in a standardized fashion. All trials were critically analyzed and
      their methodological quality evaluated. Eight studies fulfilled the pre-defined
      inclusion/exclusion criteria. Three trials (two on back pain and one on enuresis)
      were judged to be burdened with serious methodological flaws. The results of the
      three most rigorous studies (two on asthma and one on primary dysmenorrhea) do
      not suggest that spinal manipulation leads to therapeutic responses which differ
      from an inactive sham-treatment. This analysis demonstrates that sham-controlled
      trials of spinal manipulation are sparse but feasible. The most rigorous of these
      studies suggest that spinal manipulation is not associated with clinically
      relevant specific therapeutic effects.

PMID- 11576806
TI  - Is ankle-brachial blood pressure measurement of clinical utility for asymptomatic
      elderly?
AB  - The article by Abbott, et al. "Ankle-Brachial Blood Pressure in Elderly Men and
      the Risk of Stroke: The Honolulu Heart Program," further extends the strong,
      consistent association of lower ankle-brachial blood pressure ratios to the risk
      of stroke.

PMID- 11576807
TI  - Ankle-brachial blood pressure in elderly men and the risk of stroke: the Honolulu
      Heart Program.
AB  - Although low ankle/brachial blood pressure index (ABI) is a marker of generalized
      atherosclerosis in the elderly, it has not been identified as a risk factor for
      stroke. The purpose of this report is to examine the relation between ABI and
      stroke in elderly men. ABI was measured from 1991 to 1993 in 2767 men aged 71 to
      93 years in the Honolulu Heart Program without a history of stroke and coronary
      heart disease. Subjects were followed for 3 to 6 years for fatal and nonfatal
      thromboembolic and hemorrhagic stroke. During follow-up, there were 91 strokes.
      There was an age-adjusted 2-fold excess in men with an ABI < 0.9 (6.0%) versus
      men with an ABI > or = 0.9 (2.9%, P < 0.01). Thromboembolic events occurred in
      4.6% of men with an ABI < 0.9 and in 2.0% in those with an ABI > or = 0.9 (P <
      0.01). Hemorrhagic stroke was also more frequent in men with a low ABI (< 0.9)
      versus a higher ABI (1.9 vs. 0.8%, respectively). After adjusting for other
      factors, the risk of total and thromboembolic strokes increased with declining
      ABI (P = 0.019 and P = 0.004, respectively). The relation between ABI and stroke
      was similar and statistically significant in the presence and absence of diabetes
      and hypertension (P < 0.05). Findings suggest that ABI is inversely related to
      the incidence of stroke. Simple measurement of ABI in an outpatient setting could
      be an important tool for assessing the risk of stroke in the elderly.

PMID- 11576808
TI  - Logistic regression in the medical literature: standards for use and reporting,
      with particular attention to one medical domain.
AB  - Logistic regression (LR) is a widely used multivariable method for modeling
      dichotomous outcomes. This article examines use and reporting of LR in the
      medical literature by comprehensively assessing its use in a selected area of
      medical study. Medline, followed by bibliography searches, identified 15 peer
      reviewed English-language articles with original data, employing LR, published
      between 1985 and 1999, pertaining to patient interest in genetic testing for
      cancer susceptibility. Articles were examined for each of 10 criteria for proper
      use and reporting of LR models. Substantial shortcomings were found in both use
      of LR and reporting of results. For many studies, the ratio of the number of
      outcome events to predictor variables (events per variable) was sufficiently
      small to call into question the accuracy of the regression model. Additionally,
      no studies reported validation analysis, regression diagnostics, or goodness-of
      fit measures. It is recommended that authors, reviewers, and editors pay greater
      attention to guidelines concerning the use and reporting of LR models.

PMID- 11576809
TI  - Modelling time-dependent hazard ratios in relative survival: application to colon
      cancer.
AB  - The Cox model is widely used in the evaluation of prognostic factors in clinical
      research. In population-based studies, however, which assess long-term survival
      of unselected populations, relative survival models are often considered more
      appropriate. In both approaches, the validity of proportional hazard hypothesis
      should be evaluated. To explore the validity of the proportional hazard
      assumption in a population-based study of colon cancer, to propose non
      proportional hazard relative survival models and to evaluate their utility. The
      use of a piecewise proportional hazard relative survival model in colon cancer
      has shown that the effects of most clinical prognostic factors such as age,
      period of diagnosis and stage are non-proportional. The non-proportional hazard
      relative survival models developed in this article have been found to be
      efficient tools for better understanding the time-dependent aspect of prognostic
      factors.

PMID- 11576810
TI  - Statistical analysis of failure times in total joint replacement.
AB  - Time to revision is an important criterion describing the quality of implants in
      total joint surgery. Estimates of failure probabilities are required to inform a
      patient about the risk of suffering a reoperation. Also, regression models are
      used for comparing different prosthesis designs. Typically, patients dying before
      a revision are considered as censored for time to prosthesis failure. We argue
      that this technique is inadequate for estimation of failure probabilities and
      insufficient for comparison of different designs. We propose a new approach based
      on a competing risk model to account for concurrent mortality. We describe
      differences in the estimation of failure probabilities and in the interpretation
      of regression models for implant failure. Additionally, we introduce a random
      effects term in the regression model to account for potential dependencies in the
      failure times of bilaterally treated patients. The new approach is illustrated
      with fictitious data and data from an observational study conducted at a
      specialized hospital in Switzerland.

PMID- 11576811
TI  - Sensitivity and specificity of the RAND/UCLA Appropriateness Method to identify
      the overuse and underuse of coronary revascularization and hysterectomy.
AB  - There is no empirical evidence on the sensitivity and specificity of methods to
      identify the possible overuse and underuse of medical procedures. To estimate the
      sensitivity and specificity of the RAND/UCLA Appropriateness Method. Parallel
      three-way replication of the RAND/UCLA Appropriateness Method for each of two
      procedures, coronary revascularization and hysterectomy. Maximum likelihood
      estimates of the sensitivity and specificity of the method for each procedure.
      These values were then used to re-calculate past estimates of overuse and
      underuse, correcting for the error rate in the appropriateness method. The
      sensitivity of detecting overuse of coronary revascularization was 68% (95%
      confidence interval 60-76%) and the specificity was 99% (98-100%). The
      corresponding values for hysterectomy were 89% (85-94%) and 86% (83-89%). The
      sensitivity and specificity of detecting the underuse of coronary
      revascularization were 94% (92-95%) and 97% (96-98%), respectively. Past
      applications of the appropriateness method have overestimated the prevalence of
      the overuse of hysterectomy, underestimated the prevalence of the overuse of the
      coronary revascularization, and provided true estimates of the underuse of
      revascularization. The sensitivity and specificity of the RAND/UCLA
      Appropriateness Method vary according to the procedure assessed and appear to
      estimate the underuse of procedures more accurately than their overuse.

PMID- 11576812
TI  - Health-related quality of life with coronary heart disease prevention and
      treatment.
AB  - Estimating the net benefits of dyslipidemia treatment is limited by the lack of
      comprehensive and standardized information on the preference for dyslipidemia and
      coronary heart disease. In a hospital-based study, we measured the health-related
      quality of life (HRQOL) of healthy participants without dyslipidemia (n = 307)
      and with dyslipidemia (n = 251) and patients with coronary heart disease (n =
      320). Compared to the healthy participants without dyslipidemia, those with
      dyslipidemia reported lower adjusted mean scores on the Rating Scale (-2.8
      points, P = 0.02) and the SF-36 General Health Scale (-3.3 points, P = 0.02). No
      differences were observed on the Time Trade-off and the Standard Gamble Scales.
      Coronary patients reported lower scores on all preference scales and most SF-36
      scales. The causes of the small but real reduction in HRQOL reported by
      dyslipidemic individuals should be identified in order to optimize the net
      benefits of lipid therapy.

PMID- 11576813
TI  - Prevalence of disability in three birth cohorts at old age over time spans of 10
      and 20 years.
AB  - The prevalence of disability at the age of 75+ measured by the Katz Index of
      Activities of Daily Living (ADL) was compared among three birth cohorts: those
      born < or = 1903 (n = 348), those born < or = 1913 (n = 586), and those born < or
      = 1923 (n = 758). Significant risk factors for disability were female sex and
      age; the cohort effect was not significant. The prevalence rates of disability
      were 29.0% (95% CI 24.2-33.8), 34.8% (30.9-38.7), and 28.8% (25.5-32.0) for the
      first, second, and third cohorts. In the age group 75-79 years the rates were
      20.1% (95% CI 13.8-26.4), 25.5% (20.2-30.7), and 14.4% (10.6-18.1). The change
      was due to the declining disability of women. The distributions in the three
      cohorts based on the numbers of ADL limitations did not differ. As far as the
      whole aged populations were concerned, longer life was not accompanied by
      improving health.

PMID- 11576814
TI  - Cardiac rehabilitation for community-based patients with myocardial infarction:
      factors predicting discharge recommendation and participation.
AB  - Although there is substantial evidence that cardiac rehabilitation is beneficial
      for post myocardial infarction (MI) patients, such programs are currently under
      utilized. This study examined systematic criteria predicting physician referral
      to and patients' participation in cardiac rehabilitation programs. Patients
      discharged for MI were interviewed in-hospital and at 6-12 weeks post discharge
      to determine referral, participation, and completion. Stepwise logistic
      regression analyzed factors associated with rehabilitation. Factors associated
      with referral to rehab were catheterization (p < 0.001), bypass surgery (p <
      0.01), cardiologist/cardiac surgeon appointment (p < 0.02), and age (p < 0.01).
      Participation was increased for those with bypass surgery (p < 0.001), and
      referral to cardiologist or cardiac surgeon (p < 0.001). Type of provider
      significantly influences referral to and participation in cardiac rehabilitation.
      This suggests that encouragement plays a strong role in attendance for
      rehabilitation. The same strong encouragement should be given to the broader
      range of MI patients who stand to benefit from cardiac rehabilitation.

PMID- 11576815
TI  - Sample exchange to compare insulin measurements between the San Antonio Heart
      Study and the Framingham Offspring Study.
AB  - Lack of assay standardization has precluded cross-study comparison of insulin
      levels. We exchanged blood samples between the San Antonio Heart and Framingham
      Offspring Studies to compare insulin measurements. Two randomly selected
      specimens were chosen for each non-diabetic man and woman in each of the bottom
      four quintiles and top two deciles of the originally assayed fasting and 2-hour
      post-challenge insulin distributions: 48 plasma samples from Framingham, and
      after further stratification by ethnicity, 96 serum samples from San Antonio.
      Total immunoreactive insulin was originally measured in both studies; we repeated
      the identical assay on exchanged samples. Repeat assays were performed a mean
      (SD) of 7.0 (0.8) years after collection in the Framingham study and 4.6 (1.1)
      years in the San Antonio study. Repeat insulin levels were highly correlated with
      original levels for both San Antonio samples repeated in Framingham (Pearson
      r=0.923) and for Framingham samples repeated in San Antonio (r=0.959). Original
      and repeat San Antonio serum insulin levels were similar (mean fasting and 2-hour
      combined original level 154 pmol/l vs. 142 pmol/l on repeat in Framingham).
      Framingham plasma insulin levels repeated in San Antonio were substantially lower
      than original levels (120 pmol/l vs. 336 pmol/l), as were an additional 12
      samples repeat assayed in Framingham (93 pmol/l vs. 320 pmol/l). Repeat rank
      ordering in both studies was excellent: over 90% of subjects originally
      classified as hyperinsulinemic (top tertile of the combined distribution) were
      again classified as hyperinsulinemic upon repeat assay. We conclude that sample
      exchange for insulin measurement is simple and feasible. Original and repeat
      insulin levels are highly correlated; subjects originally classified as
      hyperinsulinemic remain so classified upon repeat assay. Associated regression
      curves can be used to calibrate insulin levels to a common reference standard,
      allowing epidemiology studies to compare levels of insulin and associated risk
      factors.

PMID- 11576816
TI  - Accurate case finding using linked electronic clinical and administrative data at
      a children's hospital.
AB  - To link hospital administrative data and an electronic medical record at a
      children's hospital in order to identify children with cancer admitted for fever
      and neutropenia. Hospital administrative data concerning 13,374 inpatient and
      outpatient encounters were validated against and linked to clinical data stored
      in an electronic medical record. Queries of the linked databases identified
      children with fever and neutropenia. Sensitivity and specificity of the
      experimental case-finding strategy were determined and compared to a control case
      finding strategy utilizing administrative data alone. Linking of the clinical
      record to the administrative record was achieved in 233 (99%) of the 235 records.
      Of 1680 data elements reviewed from the administrative data that were also
      potentially available in the clinical data system, 1679 (99.9%) were verified in
      the electronic medical record. The experimental strategy for case finding had a
      sensitivity of 73.1% (95% CI: 58.1, 88.3), specificity 99.6% (95% CI: 99.1, 100).
      If only administrative data such as diagnosis-related group and hospital service
      were used for case finding, both the sensitivity (P < 0.01) and specificity (P <
      0.01) were significantly lower. Linking a children's hospital administrative data
      system with clinical data is feasible and can be utilized for specific case
      finding for a common and costly condition in children.

PMID- 11576817
TI  - Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis.
AB  - Asymmetry in funnel plots may indicate publication bias in meta-analysis, but the
      shape of the plot in the absence of bias depends on the choice of axes. We
      evaluated standard error, precision (inverse of standard error), variance,
      inverse of variance, sample size and log sample size (vertical axis) and log odds
      ratio, log risk ratio and risk difference (horizontal axis). Standard error is
      likely to be the best choice for the vertical axis: the expected shape in the
      absence of bias corresponds to a symmetrical funnel, straight lines to indicate
      95% confidence intervals can be included and the plot emphasises smaller studies
      which are more prone to bias. Precision or inverse of variance is useful when
      comparing meta-analyses of small trials with subsequent large trials. The use of
      sample size or log sample size is problematic because the expected shape of the
      plot in the absence of bias is unpredictable. We found similar evidence for
      asymmetry and between trial variation in a sample of 78 published meta-analyses
      whether odds ratios or risk ratios were used on the horizontal axis. Different
      conclusions were reached for risk differences and this was related to increased
      between-trial variation. We conclude that funnel plots of meta-analyses should
      generally use standard error as the measure of study size and ratio measures of
      treatment effect.

PMID- 11576818
TI  - Discontinuation of postmenopausal hormone therapy in a Massachusetts HMO.
AB  - Long-term postmenopausal hormone therapy alleviates menopausal symptoms,
      decreases women's risk of osteoporosis and has been shown to reduce
      cardiovascular morbidity and mortality in more than 30 observational studies.
      However, nearly half of all women initiating hormone therapy discontinue within
      the first year. This study was conducted to determine the rate and predictors of
      hormone therapy discontinuation in a clinical practice setting. We identified 992
      women aged 45-59 who began hormone therapy between 1993 and 1995 in a
      Massachusetts health maintenance organization. Women were followed 2 years from
      the day they filled a prescription for estrogen. 53% discontinued hormone therapy
      by the end of the first year and one-fifth stopped after the first prescription.
      A prescription from a gynecologist (RR = 0.82, 95% CI: 0.68, 0.99) and a
      mammogram a year prior to initiation (RR = 0.75, 95% CI: 0.63, 0.89) were
      associated with a lower rate of discontinuation. Women who were using monoamine
      oxidase inhibitors (MAOI) or selective serotonin reuptake inhibitors (SSRI)
      antidepressants 3 months prior to initiation (RR = 2.07, 95% CI: 1.26, 3.39) or
      who had been enrolled in the health plan for less than 3 years (RR = 1.33, 95%
      CI: 1.10, 1.62) had an increased risk of discontinuing hormone therapy. The year
      a woman entered the cohort was also associated with a higher rate of
      discontinuation (RR = 1.40, 95% CI: 1.14, 1.74 for 1994 and RR = 1.95, 95% CI:
      1.52, 2.50 for 1995). The results indicate that long-term hormone therapy use is
      uncommon in clinical practice, particularly when a woman or her physician
      attempts to use hormone therapy as an alternative to antidepressant therapy, and
      that the rates of discontinuation of hormone therapy were rising rapidly in the
      mid-1990s.

PMID- 11576819
TI  - The effects of different kinds of user fees on prescribing quality in rural
      Nepal.
AB  - This study evaluated the effects of three different kinds of user fee on the
      quality of prescribing in rural Nepal. Using data from 33 public health
      facilities, we performed a controlled before-and-after study, comparing a fee per
      prescription (covering all drugs in whatever amounts) against one- and two-band
      fees per drug item (covering a full course of treatment for each item). With the
      one-band item fee, each item incurred the same fee; with the two-band item fee,
      more expensive items incurred a higher fee and cheaper ones a lower fee. Thirteen
      indicators of prescribing quality were evaluated based on an average of 400
      prescribing episodes per facility per year. The percentage of prescriptions
      conforming to standard treatment guidelines was 12% (95% confidence interval [CI]
      3% to 21%) and 15% (95% CI 6% to 24%) greater with the one- and two-band item
      fees, respectively, than with the fee per prescription. Prescribing quality
      improved through a reduction in the number of unnecessary, but not necessary,
      drug items prescribed per patient. Item-based fees are associated with
      significantly better prescribing quality than a fee per prescription; therefore,
      item-based fees are preferred over a fee per prescription when considering
      methods of cost recovery.

PMID- 11576821
TI  - Oral vaccination in man using antigens in particles: current status.
AB  - Over 30 publications suggest that antigens given orally to mice in biocompatible
      microspheres stimulate an immune response and, in some cases, can give rise to
      protective immunity. Of those responses in mice that have been reproduced,
      confirmation in large animal models and in Phase 1 studies has not resulted.
      Particles containing antigens given orally and mixed with soluble adjuvants like
      cholera toxin have generally not produced any better data in mice than that seen
      with mixed solutions of unprotected antigens and adjuvants. Peyer's patch M cell
      targeting of antigens in particles remains however a relatively untested
      hypothesis. While binding and uptake of M cell-targeted latex particles and
      stable liposomes by mouse M cells has been clearly shown using the mouse M cell
      specific lectin, Ulex europaeus 1 (UEA-1), a direct relationship between M cell
      particle uptake and immune outcome remains illusive. Some studies have produced
      increased serum antibodies from UEA-1- and cholera toxin B (CTB)-coated liposomes
      containing antigens. Other groups are currently working on developing novel human
      M cell ligands for attachment to stable particles for oral delivery. Use of
      untargeted antigen-containing particles with adjuvants administered by the nasal
      route remains an alternative option.

PMID- 11576822
TI  - TOGA analysis of gene expression to accelerate target development.
AB  - With the availability of new technologies for analysis of gene expression, drug
      targets may now be identified through more focused rational approaches. We have
      developed an extremely sensitive, reproducible, and accurate method called TOGA,
      enabling analysis of nearly all genes within an RNA sample. This technology can
      be used to identify genes regulated in a great variety of situations. For
      example, we have been able to find genes with expression restricted to specific
      brain regions, and in a recent example, we found a gene regulated in specific
      brain regions in response to clozapine treatment. These studies will quickly lead
      to identification of genes critical to specific biological and clinical
      processes, accelerating the development of new targets and therapies.

PMID- 11576823
TI  - Random sampling or 'random' model in skin flux measurements? [Commentary on
      "Investigation of the mechanism of flux across human skin in vitro by
      quantitative structure-permeability relationships"].
AB  - Transdermal therapy receives increasing attention as an attractive alternative to
      traditional drug delivery. Unfortunately the exact algorithm of transdermal
      permeation that could guide medicinal chemists towards delivery optimization at
      an early stage of the drug design process still remains to be decoded. This paper
      discusses some major hurdles on the way to full understanding of Quantitative
      Structure-Activity Relationships (QSAR) of skin permeation. From the statistical
      perspective, a recently published combined data set is found to be inappropriate
      with respect to the distribution of major molecular descriptors, and therefore
      should be approached cautiously as a source for QSAR model training and in
      modelling of occupational and environmental skin exposures.

PMID- 11576824
TI  - Chitosan and its derivatives in mucosal drug and vaccine delivery.
AB  - Numerous studies have demonstrated that chitosan and their derivatives (N
      trimethyl chitosan, mono-N-carboxymethyl chitosan) are effective and safe
      absorption enhancers to improve mucosal (nasal, peroral) delivery of hydrophylic
      macromolecules such as peptide and protein drugs and heparins. This absorption
      enhancing effect of chitosans is caused by opening of the intercellular tight
      junctions, thereby favouring the paracellular transport of macromolecular drugs.
      Chitosan nano- and microparticles are also suitable for controlled drug release.
      Association of vaccines to some of these particulate systems has shown to enhance
      the antigen uptake by mucosal lymphoid tissues, thereby inducing strong systemtic
      and mucosal immune responses against the antigens. The aspecific adjuvant
      activity of chitosans seems to be dependent on the degree of deacetylation and
      the type of formulation. From the studies reviewed it is concluded that chitosan
      and chitosan derivatives are promising polymeric excipients for mucosal drug and
      vaccine delivery.

PMID- 11576825
TI  - Synthesis, in vitro and in vivo cytotoxicity, and prediction of the intestinal
      absorption of substituted 2-ethoxycarbonyl-imidazo[2,1-b]benzothiazoles.
AB  - The imidazobenzothiazole compounds 3-17 together with the imidazobenzoxazole 18,
      and the imidazobenzoimidazole 19 were prepared and their cytotoxic activity
      evaluated at the National Cancer Institute (NCI) for testing against a panel of
      approximately 60 tumor cell lines. Compounds 5, 7, 8, and 16 exhibited
      interesting in vitro cytotoxic activity. The most active imidazobenzothiazole
      derivative 8 was further evaluated as a cytotoxic agent in the hollow fiber assay
      and showed a score greater than the minimum values for xenograft testing together
      with a net cell kill. Comparison with the results displayed in the in vivo assay
      by standard antitumor drugs in clinical use revealed a significant in vivo
      activity of the benzothiazole compound. COMPARE analyses for compounds 4-19
      against the NCI's standard agent database show poor or no correlation, and it
      might suggest for these compounds a mechanism of action unrelated to that of any
      known drug. Furthermore, the benzothiazole 8 did not show significant antitumor
      activity in a panel of two xenotransplanted tumors (i.e. colon and non-small cell
      lung tumors). By computing the polar surface area of compounds 3-19 with the
      MAREA computer program it was established that the most active compounds 5, 7, 8,
      and 16 should experience good intestinal permeability.

PMID- 11576826
TI  - Evaluation of skin sensitization potential of melatonin and nimesulide by murine
      local lymph node assay.
AB  - Melatonin is a good candidate for transdermal delivery considering its short
      plasma half life, low molecular weight and a favorable octanol:water partition
      coefficient. Nimesulide is a nonsteroidal anti-inflammatory agent used orally and
      rectally for inflammatory disorders. The objective of this study was to
      investigate the skin sensitization potential of melatonin and nimesulide using
      the standard murine local lymph node assay (LLNA). Melatonin (0.5, 2.5, 5.0 and
      10.0%, w/v) and nimesulide (0.5, 2.5, 5.0 and 10.0%, w/v) dissolved in
      acetone:olive oil (4:1, AOO) was applied (25 microl) on the dorsal surface of
      each ear of female CBA/Ca mice for three consecutive days. On the sixth day,
      [3H]methyl thymidine was administered intravenously and the uptake of [3H]methyl
      thymidine (dpm) by the draining lymph nodes was determined by established
      methods. Dinitrochlorobenzene (DNCB, 0.25%, w/v) and para-aminobenzoic acid
      (PABA, 2.5%, w/v) were used as positive and negative control, respectively. The
      mean dpm obtained with melatonin and nimesulide treatment at all concentrations
      were not significantly different (P>0.05) from that of AOO. The stimulation index
      (SI) values of melatonin and nimesulide at different concentrations were close to
      1. The results of the present study using the standard LLNA approved by US
      Interagency Coordinating Committee in the Validation of Alternative Methods
      (ICCVAM) indicate that melatonin and nimesulide are not skin sensitizers.
      However, since LLNA has shown false negatives with many drugs, clinical trials
      are certainly needed to exclude the possibility of a weak or delayed type skin
      sensitization reaction. Further studies using modified LLNA procedures (extended
      exposure, alternative vehicle systems, pre-abrasion, etc.) may be useful in
      identifying the weak or delayed type skin sensitization reactions.

PMID- 11576827
TI  - Synthesis, hydrolysis kinetics and anti-platelet effects of isosorbide
      mononitrate derivatives of aspirin.
AB  - Two isomeric aspirin derivatives of isosorbide-5-mononitrate (ISMN) were prepared
      and evaluated as potential mutual prodrugs of aspirin and nitric oxide. The
      hydrolysis of both compounds was studied in pH 7.4 phosphate buffer solution,
      buffered alpha-chymotrypsin solution and 10% buffered rabbit plasma. The
      benzodioxin-4-one derivative was hydrolysed to salicylic acid and ISMN acetate in
      buffer solution (t(1/2) 32.1 h), 10% buffered rabbit plasma (t(1/2) 25.7 min) and
      alpha-chymotrypsin (t(1/2) 86.6 min). The carboxylic acid ester derivative ISMNA
      was hydrolysed via the salicylate ester in buffer solution (t(1/2) 48.5 h) but
      was rapidly and almost exclusively hydrolysed to aspirin and ISMN in plasma
      solution (t(1/2) 2.8 min). The hydrolysis appeared to be enzyme mediated as it
      was suppressed by co-incubation with eserine. ISMNA was evaluated for its ability
      to inhibit platelet aggregation in rabbit PRP in response to the following
      agonists: arachidonic acid (AA) (100 microM), ADP (1.2 microM), phorbol ester
      (0.5 microM), platelet activating factor (PAF) (5 nM) and the thromboxane mimic
      U46619 (1.5 microM). ISMNA suppressed platelet response to AA at 1 microM whereas
      10 microM aspirin showed no inhibitory effects.

PMID- 11576828
TI  - In vitro permeation profile of a local anaesthetic compound from topical
      formulations with different rheological behaviour--verified by in vivo efficacy
      data.
AB  - The object of this study was to develop a topical cream of suitable consistency,
      i.e. with a high apparent yield stress, without affecting the in vitro permeation
      profile and the subsequent in vivo efficacy of the formulation. Different
      formulations of a model compound were manufactured, an oil-in-water (o/w)
      emulsion, a cream consisting of the o/w emulsion thickened with various
      concentrations of neutralised Carbopol934P gel, and a semisolid water-in-oil
      (w/o) emulsion. Rheological measurements were performed giving the apparent yield
      stress of the formulations. The in vitro permeation rate of the compound was
      measured, using static diffusion cells with both guinea pig and human skin as
      membrane. The o/w emulsion without polymer was used as reference. The in vivo
      efficacy of the formulations was investigated on guinea pigs by the pinprick
      method. The apparent yield stress of the w/o emulsion was in the same range as
      that of the most viscous o/w cream while the o/w emulsion behaved as a Newtonian
      liquid. Furthermore, the yielding property of the w/o emulsion was not as
      temperature-sensitive as that of the o/w cream. The permeation rate of the
      compound from the two emulsions, o/w and w/o, was similar at 6% (w/w), while the
      o/w cream resulted in a significantly lower permeation rate at the same
      concentration. The two emulsions produced sufficient and comparable in vivo
      efficacy, while the o/w cream was less efficient. In conclusion, a reversed-phase
      emulsion may be used to produce the appropriate apparent yield stress, without
      affecting the in vivo efficacy of the formulation. The viscosity of a w/o
      emulsion depends on the amount of the aqueous phase and the degree of dispersity.
      Thus, the transport of the active compound is not prevented by the excipients
      present in the formulation, as is the case for the o/w cream.

PMID- 11576829
TI  - A dynamic in vitro lipolysis model. II: Evaluation of the model.
AB  - A lipolysis model was characterised and evaluated by investigating the
      composition of the aqueous phase and the concentration of probucol and danazol in
      the aqueous phase. Effects of bile salt levels at 5, 10, 20, and 30 mM were
      investigated. Samples were taken at 0%, 50%, 75% and 95% hydrolysis of the
      triglycerides, and the aqueous phases were isolated by ultra-centrifugation,
      whereby the concentrations of bile salts, fatty acids, mono-, di-, triglycerides,
      and drug substances were measured. At high Ca(2+)-concentrations, bile salts were
      believed to precipitate with Ca(2+). The concentration of lipolytic products
      (fatty acids + monoglycerides) was dependent on the bile salt concentration. The
      ratio between lipolytic product and bile salts was 1.55+/-0.09 (S.D.). This ratio
      is equivalent to mixed bile salt micelles and vesicles in equilibrium. The
      aqueous solubility of probucol and danazol was increased in the presence of bile
      salts. The concentration of danazol in the aqueous phase was dependent on the
      solubilisation capacity of the aqueous phase. In the case of probucol, the
      concentration in the aqueous phase was dependent on the partition of probucol
      between the aqueous phase and the remaining triglyceride phase. This difference
      between danazol and probucol was attributed to the effect of different
      lipophilicity.

PMID- 11576830
TI  - Plasticisation of amylodextrin by moisture. Consequences for compaction behaviour
      and tablet properties.
AB  - PURPOSE: Amylodextrin, a starch-based controlled release excipient, spontaneously
      absorbs moisture during storage. The aim of this study was to investigate
      plasticisation of amylodextrin by moisture and its effect on compaction and
      tablet characteristics. METHODS: The glass transition temperature (T(g)) of
      amylodextrin powders with moisture fractions (x(w)) 0.070<x(w)<0.40 was studied
      by conventional and modulated DSC. Elastic modulus and yield stress were
      determined from compressive stress-strain experiments. Compaction behaviour was
      studied at 3 and 300 mm/s using a compaction simulator. RESULTS: The T(g) of
      amylodextrin-water blends showed a smooth reduction with increasing x(w),
      equalling room temperature at x(w)=0.19. Experimentally obtained T(g) values were
      close to temperatures as predicted by the Gordon-Taylor/Kelley-Bueche model and
      the modified Couchman-Karasz model. The elastic modulus decreased steeply between
      x(w)=0.17 and 0.23. Compaction experiments showed that moisture facilitated
      consolidation due to increasing powder compressibility and reduced compact
      relaxation. However, at x(w)=0.23, compressibility was reduced and relaxation
      significantly higher due to the rubbery character of this powder. Consequently,
      the lowest tablet porosities were obtained around x(w)=0.15. Although decreasing
      porosities enhanced tablet strengths, the maximum obtainable tablet strengths
      decreased with moisture due to reduced particle bonding and lowering of the
      elastic modulus. CONCLUSION: Moisture largely affects the visco-elastic and
      compaction characteristics of amylodextrin. Hence, control over moisture content
      is essential to produce tablets with reproducible porosity, strength and
      dissolution characteristics.

PMID- 11576831
TI  - "What really goes on in Brussels?".

PMID- 11576832
TI  - Editorial comment on detection of Epstein-Barr virus DNA in peripheral blood of
      paediatric patients with Hodgkin's disease by real-time polymerase chain reaction
      by Wagner and colleagues.

PMID- 11576834
TI  - The impact of age on local control in women with pT1 breast cancer treated with
      conservative surgery and radiation therapy.
AB  - The aim of the study was to evaluate the importance of young age with regard to
      local control in a prospective cohort of 1085 women with pathological T1 tumours
      treated with breast conservative treatment (BCT). Patients were divided into two
      age groups: 40 years or younger, 7.8%, and older than 40 years, 92.2%. With a
      median follow-up of 71 months, the local recurrence rate was 10.6% in women < or
      =40 years, and 3.7% in older women. The local recurrence-free survival (LRFS) was
      significantly different for the two age groups, respectively 89%, < or =40 years,
      and 97.6%, >40 years (P=0.0046). A separate analysis showed a significantly
      decreased LRFS for young women with a positive family history, 75.4% versus 98.4%
      5-year LRFS for older women. A worse LRFS for young women with a negative lymph
      node status was also observed, respectively 84% versus 98% 5-year LRFS (both
      P<0.001). In a multivariate analysis, taking into account the pre-treatment and
      treatment factors, age < or =40 years, was the only significant predictor of a
      decreased LRFS. Thus, young age is an important factor in relation to local
      control. In a subset analysis, this significant adverse effect of young age on
      outcome appears to be limited to the node-negative patients and those with a
      positive family history. To date, there is no evidence that young women with pT1
      breast cancer, treated by mastectomy have an improved outcome when compared with
      those treated with conservative surgery and radiotherapy. Taking into account
      results from a subset analysis suggests that giving systemic therapy to a
      subgroup of women who are < or =40 years, node-negative and/or have a positive
      family history might give a better local control.

PMID- 11576833
TI  - STI571: a magic bullet?

PMID- 11576835
TI  - A weekly 24-h infusion of high-dose 5-fluorouracil (5-FU)+leucovorin and bi
      weekly cisplatin (CDDP) was active and well tolerated in patients with non-colon
      digestive carcinomas.
AB  - In patients with non-colon digestive carcinomas, various schedules and doses of 5
      fluorouracil (5-FU) and leucovorin combined with cisplatin (CDDP) have been used
      extensively. The present study explored the toxicity and activity of a weekly 24
      h infusion of high dose 5-FU modulated by high dose leucovorin with bi-weekly
      CDDP. 59 patients with measurable disease were treated with a weekly infusion of
      high dose 5-FU (2 or 2.6 g/m2)+leucovorin 500 mg/m2 for 6 weeks and a bi-weekly
      dose of CDDP (50 mg/m2). All patients had metastatic or locoregionally advanced
      disease and had a performance status < or =3. All patients were evaluable for
      toxicity and 58 for response. Toxicity was different according to the schedule of
      5-FU. Serious adverse events occurred most frequently when 5-FU was given at a
      dose of 2.6 g/m2 with a high incidence of grade 3/4 neutropenia (16%) and febrile
      neutropenia (13%), and led to dose reductions in both CDDP and 5-FU in 13
      patients (34%). For patients who started 5-FU at a dose of 2 g/m2, no reduction
      in 5-FU was required, and only 4 patients required a dose reduction of CDDP
      (19%). Grade 3/4 neutropenia was seen in 10% of patients of this group and only 1
      patient required hospitalisation for febrile neutropenia. Other grade 3/4
      toxicities were rare in both groups. Renal toxicity was infrequent and mild and
      did not require dose adjustments. The overall response rate was 33%; 19 patients
      achieved a partial responses (PR). No patient had a complete response (CR). The
      median duration of response was 5.7 months (range 2-24 months) and the median
      survival was 7.9 months ( range: 1-30, 95% confidence interval (CI): 7-9). The
      combination of weekly 24-h infusion of high dose 5-FU with leucovorin and bi
      weekly cisplatin seems a well-tolerated and active treatment in non-colon
      digestive carcinomas. A dose of 2 g/m2 of 5-FU seems to be recommended.

PMID- 11576836
TI  - First-line chemotherapy with docetaxel for unresectable or metastatic carcinoma
      of the biliary tract. A multicentre phase II study.
AB  - The purpose was to evaluate the efficacy and safety profile of docetaxel as first
      line chemotherapy for patients with locally advanced or metastatic biliary tract
      carcinoma. 25 chemotherapy-naive patients with unresectable or metastatic biliary
      tract carcinoma were entered into this phase II trial. Docetaxel was given at the
      dose of 100 mg/m2 as a 1-h infusion on day 1, after appropriate premedication
      with dexamethasone; treatment was repeated every 21 days. Patients were assessed
      for response every three chemotherapy cycles. 24 patients were evaluable for
      response and 25 for toxicity. A total of 98 cycles were administered with a
      median of three cycles/patient. Two complete (CR=8%) and three partial (PR=12%)
      responses were observed (overall response rate: 20%; 95% confidence interval
      (C.I.) 4-36%); in addition, 6 (24%) patients had stable disease and 14 (58%)
      progressive disease. With a median follow-up of 8 months, the median duration of
      response was 4 months, the median time to tumour progression (TTP) was 6 months
      and the overall median survival was 8 months. The 1-year survival rate was 26%.
      Grade 3 and 4 granulocytopenia occurred in 36 and 20% of the patients,
      respectively, and febrile neutropenia was observed in 16% of them; there were no
      treatment-related deaths. Grade 2-3 fatigue was reported in 24% of patients.
      These results indicate that docetaxel is an active drug against adenocarcinomas
      of the biliary tract.

PMID- 11576837
TI  - mRNA expression of matrix metalloproteases and their inhibitors differs in
      subtypes of renal cell carcinomas.
AB  - Altered expression of matrix metalloproteases (MMPs) and their inhibitors, the
      tissue inhibitors of matrix metalloproteases (TIMPs), has been demonstrated in
      various tumour tissues. mRNA expression patterns of MMP-1, MMP-2, MMP-3, MMP-9,
      MMP-11, MMP-12, MMP-14 and TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were evaluated by
      quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in 30 renal
      cell carcinomas (RCC), as well as in the surrounding tissues. Expression of the
      MMPs was significantly stronger in the carcinomas than in non-malignant tissues.
      High levels were demonstrated particularly in clear cell RCCs (CC-RCC). Except
      for MMP-1, MMP expression in the papillary RCCs (P-RCC) was, for most MMPs,
      significantly lower. Expression of the TIMPs in malignant cells of both subtypes
      was weak, with the exception of TIMP-4 which was strongly expressed in the P-RCCs
      and downregulated in the CC-RCCs. The latter was correlated with chromosomal loss
      of 3p, harbouring the TIMP-4 gene locus. In conclusion, deregulated expression of
      the MMPs and TIMPs in RCCs differs according to histology, grade, size and
      cytogenetic characteristics, suggesting that MMP and TIMP expression patterns
      play an important role for the typical histomorphological features of RCC
      subtypes and their respective biological behaviour.

PMID- 11576838
TI  - Bone marrow micrometastases in patients with stage I-II localised prostate
      cancer.
AB  - Prostate cancer commonly metastasises to the bones. Detection of bone marrow
      micrometastases (BMM) may give important information that helps define treatment
      strategies. This study was undertaken to analyse BMM in early prostate cancer
      patients and to determine the accuracy of immunohistochemical (IHC) and
      morphological methods in detecting cancerous cells. Preoperative core bone marrow
      biopsy (BMB) was performed in 103 patients with T1-2, N0, M0 prostate cancer
      after neoadjuvant androgen blockade. BMB were examined by IHC using monoclonal
      antibodies for cytokeratins (CK) (18, 19, PAN) and by cytomorphology of IHC
      positive cells. In 103 patients, BMM were detected in 2 cases (2%) and an
      additional 3 cases (3%) were classified as suspicious. IHC alone revealed
      positive cells in 19 patients (18%). Cytomorphology disclosed IHC false-positive
      staining of some apparently normal bone marrow elements such as plasmocytes. The
      study shows a rather low rate of BMM in early prostate cancer. It also stresses
      the importance of cytomorphology as an adjunct to IHC as IHC alone may not be
      sufficient and appropriate for BMM detection.

PMID- 11576839
TI  - Detection of Epstein-Barr virus DNA in peripheral blood of paediatric patients
      with Hodgkin's disease by real-time polymerase chain reaction.
AB  - Hodgkin's disease (HD) is commonly associated with latent Epstein-Barr virus
      (EBV) infection. The aim of our study was a detailed molecular analysis of the
      EBV status in the peripheral blood of paediatric patients with HD. Blood samples
      from HD patients were examined before (n=28) and after treatment (n=12). The
      control group consisted of 20 healthy children and 10 immunosuppressed children
      with primary EBV infection. EBV load in plasma and peripheral blood mononuclear
      cells (PBMC) were determined by real time quantitative polymerase chain reaction
      (RQ-PCR) as recently described. Before treatment, EBV DNA was detected in the
      plasma of 13/24 EBV-seropositive HD patients, whereas in plasma of healthy
      controls no EBV DNA was detectable (P<0.001). After treatment, no EBV genomes
      were found in the plasma of 6 HD patients in stable and complete remission. In
      contrast, 2/5 HD patients with relapse of disease were positive for EBV DNA in
      the plasma. In PBMCs, no differences were found in EBV load measured in HD
      patients before or after treatment and healthy controls. A high EBV load was
      found in both the plasma and PBMCs of all immunosuppressed patients with primary
      EBV infection. Thus, EBV DNA detection in the plasma of paediatric HD patients
      might be of value for non-invasive diagnostic, prognostic and follow-up tests for
      HD.

PMID- 11576840
TI  - Long-term follow-up following childhood cancer: maximising the contribution from
      nursing.

PMID- 11576843
TI  - Predicting stages of adoption of mammography screening in a general population.
AB  - This study assessed predictions of the Transtheoretical Model (TTM) of behaviour
      change applied to mammography screening in a random sample of 909 Swiss women
      aged 40-80 years. We examined stages of mammography adoption, positive and
      negative attitudes toward screening (pros, cons and decisional balance), and
      additional predisposing, enabling and reinforcing characteristics. The stage of
      mammography adoption was defined for 827 women, of whom 46.9% reported on
      schedule screening (action 10.2%, maintenance 29.7%, relapse risk 7.0%) and 53%
      did not (precontemplation 23.1%, contemplation 13.5%, relapse 16.4%). Independent
      factors associated with more advanced stages (from precontemplation to
      maintenance) were high pros, low cons, belief that mammography screening is
      recommended every 2 years, high objective risk of breast cancer, being married
      and higher income. Independent correlates of stage regression (from
      action/maintenance to relapse) were high cons, belief that mammography screening
      is recommended every 4 years or not at all and not being married. Perceived
      utility of an organised screening programme and reluctance to pay for a mammogram
      were independently associated with only certain transitions between stages of
      adoption. Our results confirm the applicability of the TTM to mammography
      screening in a European context. They also suggest that constructs other than
      pros and cons may be useful in predicting mammography use.

PMID- 11576844
TI  - Familial testicular cancer and second primary cancers in testicular cancer
      patients by histological type.
AB  - The Swedish Family-Cancer Database was used to assess familial cancer risks in
      first-degree relatives and the risks of second primary cancers in testicular
      cancer patients by the histological type of their testicular cancers.
      Standardised incidence ratios (SIRs) were employed to estimate cancer risks.
      Among 4650 patients, 1.3% were familial testicular cancer. Seminomas showed a 10
      years later median age of onset than teratomas (30 versus 40 years). The familial
      risks of testicular cancer were 3.8 for fathers, 8.3 for brothers and 3.9 for
      sons; they were similar for the two histologies. The fraternal risks were
      elevated 2- to 2.8-fold for pure histologies compared with the mixed histologies.
      Significantly increased risks for subsequent cancers were observed in the
      stomach, pancreas, testis, kidney, bladder, thyroid and connective and lymphatic
      tissues in the patients. Our data support the contention that genetic
      predisposition is one of the major contributors to familial and multiple
      testicular cancers.

PMID- 11576845
TI  - Second primary neoplasms after 19281 endocrine gland tumours: aetiological links?
AB  - The nationwide Swedish Family-Cancer Database of 9.6 million individuals was used
      to analyse the development of second neoplasia after 6909 thyroid and 12697 other
      endocrine tumours. Tumour cases were retrieved from the Swedish Cancer Registry
      from 1958 to 1996. The risk of a second endocrine tumour was markedly increased
      compared with first endocrine tumour; e.g. the standardised incidence ratios
      (SIRs) were well over 10 for adrenal tumours after thyroid cancer, and vice
      versa. Familial risks were higher for the development of second compared with
      first neoplasms, and the SIRs for men were usually higher than those for women.
      Many increases between different endocrine glands can probably be ascribed to
      known cancer syndromes. Even cancers at some other sites were increased after the
      development of primary endocrine tumours. Notably, small intestinal carcinoids
      were increased after thyroid and other endocrine tumours, and brain menigiomas
      were increased after parathyroid and pituitary adenomas. These novel associations
      suggest shared risk factors for these sites. However, many endocrine tumours are
      benign and the diagnosis of the first tumour may increase the likelihood of a
      second diagnosis.

PMID- 11576846
TI  - Survival of patients with primary CNS tumours in Estonia.
AB  - We studied a population-based survey that included 1417 patients with a primary
      central nervous system (CNS) tumour diagnosed in Estonia between 1986 and 1996.
      Survival rates at 1 and 5 years and median survival by histology and patient's
      age at diagnosis were estimated. Median survival time for all tumours was 33.2
      months and 1- and 5-year survival rates were 59.3 and 46.0%, respectively. In
      multivariate analysis, younger age, better clinical condition (i.e. a Karnofsky
      Performance Status (KPS) score of 60 and more) and tumour histology were all
      dependent prognostic factors for better survival. Risk of death was more than 8
      times greater for glioblastoma (Risk Ratio (RR) 8.31) and approximately seven
      times greater for anaplastic astrocytoma (RR 7.22) and other gliomas (RR 5.74)
      compared with meningiomas. Comparing the first (1986-1989) and the third (1994
      1996) time periods, statistically significant improvements in survival occurred
      for all tumours and astrocytomas. Declines in survival during the second period
      (1990-1993) were statistically significant for all the tumour groups, but the
      most striking decrease took place in patients with glioblastoma. Age-specific
      rates showed that the increase in survival was more evident for patients aged
      between 45 and 64 years.

PMID- 11576847
TI  - A founder mutation of the BRCA1 gene in Western Sweden associated with a high
      incidence of breast and ovarian cancer.
AB  - The aim of this study was to describe and characterise a founder mutation of the
      BRCA1 gene in western Sweden. Of 62 families screened for BRCA mutations, 24 had
      BRCA1 mutations and two had BRCA2 mutations. Tumours that occurred in family
      members were histologically reviewed and mutational status was analysed using
      archival paraffin-embedded tissues. The same BRCA1 mutation, 3171ins5, was found
      in 16 families who were clustered along the western coast of Sweden. Mutation
      analysis revealed a maternal linkage in 13 families and a paternal linkage in 3.
      There was complete agreement between mutation analysis results obtained from
      blood and archival tissues. The penetrance of breast or ovarian cancer by age 70
      years was estimated to be between 59 and 93%. There were no differences in
      survivals between breast or ovarian cancer patients with the mutation and age
      matched controls. Thus, a predominant BRCA1 gene founder mutation associated with
      a high risk of breast and ovarian cancer has been identified and found to occur
      in a restricted geographical area, thereby allowing timely and cost-effective
      mutation screening using blood samples or archival histological material.

PMID- 11576848
TI  - Immunotherapy of C3H/HeJ mammary adenocarcinoma with interleukin-2, mistletoe
      lectin or their combination. effects on tumour growth, capillary leakage and
      nitric oxide (NO) production.
AB  - Clinical application of interleukin (IL)-2-based immunotherapy of cancer has been
      limited by a major side-effect known as 'capillary leak syndrome', resulting from
      nitric oxide (NO) overproduction. A galactoside-specific lectin from Viscum album
      L. (VAA) has been reported to induce certain lymphokines and upregulate IL-2
      receptors on lymphocytes. Present study was, therefore, designed to compare the
      effects of combination therapy with IL-2 (10(4) Cetus units/mouse,
      intraperitoneal (i.p). every 8 h, given as 5 day rounds per week, for one or two
      rounds) and VAA (1 ng/kg subcutaneous (s.c.), biweekly) with those of IL-2 or VAA
      therapy alone in C3H/HeJ female mice bearing s.c. transplants of a highly
      metastatic C3L5 mammary adenocarcinoma. IL-2 therapy alone reduced tumour growth
      and metastasis, but caused significant water retention indicative of capillary
      leakage in the kidneys after both rounds of therapy, whereas pleural effusion was
      only evident after the first round and not the second round. A sharp rise in the
      systemic NO levels after the first round, followed by a decline after the second
      round of IL-2 therapy suggested a causal relationship of increased NO levels to
      pleural effusion. A strong immunostaining for nitrotyrosine (a marker for the
      production of peroxynitrite) was noted in the renal tubules at the end of both
      rounds of therapy suggestive of a causal association of this toxic NO-metabolite
      with capillary leakage in the kidneys. Addition of VAA to IL-2 therapy had no
      effect on any of the above parameters. Unexpectedly, however, VAA therapy alone
      stimulated tumour growth as well as lung metastases. NO induction in the C3L5
      cells by VAA was excluded as a possible reason for this stimulation. Present
      results suggest the need for exercising caution in the use of VAA as an
      immunoadjuvant in human cancer therapy.

PMID- 11576849
TI  - Methaemoglobin enhances the proliferation of transformed human epithelial cells:
      a possible outcome of neovascularisation and haemorrhage in tumours?
AB  - The effect of human methaemoglobin (metHb), possibly derived from extravasated
      red blood cells in tumours showing neovascularisation and haemorrhage, on the
      growth of transformed human epithelial cells was investigated. MetHb stimulated
      the growth of immortalised epithelial cells or transformed cells at precrisis
      stage (cells have bypassed M1, but not M2, the two mortality checkpoints). The
      stimulatory effect was due to the release of haemin from metHb that was isolated
      by a Sephadex column and identified by its characteristic light absorption
      spectrum. Although all the degradation products of haemin are currently known to
      be physiologically significant, only ferric iron derived from metHb or haemin
      could stimulate cell growth. High concentrations of metHb or haemin inhibited
      cell growth possibly due to the generation of high concentrations of bilirubin.
      However, bilirubin formed in the cells of human body is known to be transported
      to the liver for further processing and excretion. Haemoglobin oxidised to where
      tumours show neovascularisation and haemorrhage likely contributes significantly
      to the increased proliferation of cancerous cells.

PMID- 11576850
TI  - The antitumour agent 5,6-dimethylxanthenone-4-acetic acid acts in vitro on human
      mononuclear cells as a co-stimulator with other inducers of tumour necrosis
      factor.
AB  - 5,6-dimethylxanthenone-4-acetic acid (DMXAA), currently in phase I trials,
      demonstrates excellent activity against transplantable murine tumours with
      established vasculature. The induction of cytokines, particularly of tumour
      necrosis factor (TNF), appears to be critical to its action. We investigated TNF
      induction by DMXAA in cultured human peripheral blood leucocytes (HPBL). TNF was
      measured by an enzyme-linked immunosorbent assay after 8 h, and NF-kappaB
      induction by electrophoretic mobility shift assays (EMSA) after 2 h. DMXAA (800
      microg/ml) had no effect alone on TNF production but augmented, by up to 4-fold,
      the ability of bacterial lipopolysaccharide (LPS) to induce TNF. Previously
      reported results showing TNF production by DMXAA alone were traced to the
      presence in an earlier batch of DMXAA of a small amount of LPS, the action of
      which could be blocked by polymyxin B. DMXAA stimulated TNF production by
      deacylated LPS, which alone had little effect. An antibody (MEM-18) to the CD14
      receptor, while blocking the induction of TNF by LPS, enabled DMXAA to both
      synthesise TNF and induce NF-kappaB. The structurally related drug, flavone
      acetic acid (FAA), did not induce TNF or synergise with anti-CD14 antibody. DMXAA
      strongly augmented the ability of suboptimal concentrations of interleukin-1 (IL
      1) (25 ng/ml), okadaic acid (OA) (20 ng/ml) and phorbol-12-myristate-13-acetate
      (PMA) (5 ng/ml) to induce TNF production, suggesting that it affects multiple
      pathways converging on NF-kappaB activation. Sodium salicylate, a drug reported
      to inhibit the beta-subunit of IkappaB kinase (IKK), appeared to competitively
      inhibit TNF production by DMXAA in the presence of anti-CD14 antibody. Taken
      together, the results indicate DMXAA acts in vitro on HPBL to co-stimulate TNF
      production by a wide variety of agents, and suggests that IKK is the target that
      mediates this action.

PMID- 11576851
TI  - Extended-term effects of head and neck irradiation in a rodent.
AB  - Radiotherapy to the head and neck is a common treatment for malignancies of the
      region. Unfortunately, exposure to irradiation often results in a variety of
      complications, most of which are localised and expressed in the short term
      following irradiation. However, prolonged and systemic effects may have greater
      clinical importance as the survival rate of head and neck irradiated patients is
      increasing yearly. Six groups of 18-20 rats were evaluated during a 1 year study.
      The non-irradiated control group was compared with 2.5 Gy, 5, 7.5, 10 and 15 Gy
      irradiated groups. We found a dose-dependent reduction in both survival and body
      weight in our rat models following a delayed, prolonged and chronic process.
      Dying animals were emaciated, dehydrated and starved, and many were blind and
      immunocompromised. While the exact underlying mechanism of this delayed, but
      devastating, phenomenon has not yet been determined, the delayed xerostomia
      inflicted on these animals may, at least partially, explain it. The clinical
      implications for head and neck patients require further evaluation, but our data
      should be considered, in the context of the available evidence for the long-term
      effects of head and neck irradiation in humans.

PMID- 11576852
TI  - Transcriptional activity of human papillomavirus type 16 variants having
      deletions in the long control region.
AB  - Transcription of the E6 and E7 viral oncogenes of human papillomavirus (HPV) type
      16 is regulated by the P97 major early promoter, and enhancer and silencer
      elements found in the long control region (LCR). In this study, we tested the
      transcriptional activity of natural HPV 16 variants having long deletions in the
      LCR. The HPV 16 LCR regions were amplified from invasive cervical cancer
      specimens, and cloned into the reporter vector pALuc. Transcriptional activity of
      the different clones was measured by luciferase test after transient transfection
      into HeLa cells. The deletions found in the LCR encompassed parts of the enhancer
      and either the YY1-specific silencer alone or together with the CDP-specific
      silencer. The transcriptional activity of these deletion variants were usually
      reduced compared with that of the corresponding full-length clones. However, a
      deletion variant lacking the whole enhancer and both silencer regions retained
      substantial enhancer activity on the P97 promoter. These results point to the
      existence of a novel context-dependent enhancer element in the 5' LCR of HPV 16.

PMID- 11576853
TI  - Cell growth inhibition, G2M cell cycle arrest and apoptosis induced by the
      imidazoacridinone C1311 in human tumour cell lines.
AB  - The cytotoxic activity of the imidazoacridinone C1311 was assessed on two ovarian
      cancer cell lines (A2780, OAW42) and one osteogenic sarcoma cell line (U2-OS) and
      their sublines (A2780Cp8, OAW42-MER and U2-OS-R) with experimentally induced
      resistance to cisplatin. A 1-h exposure to C1311 significantly inhibited the
      growth of all cell lines, with IC50 values ranging from 0.50 +/-0.11 to 4.10+/
      0.36 microM. No or only partial cross-resistance was found between C1311 and
      cisplatin in the different cell lines. Treatment with equitoxic (IC50) C1311
      concentrations consistently induced accumulation of cells in the G2M phase. The
      cyclin B1-associated p34(cdc2) kinase activity in cells arrested in G2M was
      superimposable to that of control cells in the OAW42-MER and U2-OS cell lines,
      whereas a reduction of cdc2 catalytic activity was observed in OAW42 and U2-OS-R
      cells. Exposure to C1311 (IC50) induced apoptosis in the U2-OS and U2-OS-R cell
      lines, whereas in the OAW42 and OAW42-MER cell lines there was a negligible
      percentage of apoptotic cells. In U2-OS, U2-OS-R and OAW42 cells, C1311 induced
      an increase in p53 expression and an increase in p21waf1 protein, whereas p53
      failed to transactivate p21waf1 in OAW42-MER cells. An almost complete abrogation
      of bcl-2 was observed in U2-OS-R cells in correspondence with the peak of
      apoptosis induction. Our results indicate that C1311 is active against human
      ovarian cancer and osteogenic sarcoma cells and is not cross-resistant with CDDP.
      Moreover, C1311 blocks cells in the G2M phase and induces apoptosis in a small
      percentage of osteogenic sarcoma cells.

PMID- 11576855
TI  - 6th International Symposium on Biological Therapy of Cancer: From Basic Research
      to Clinical Application. Munich, Germany, 12-15 September 2001. Abstracts.

PMID- 11576856
TI  - Is transdermal drug delivery research still important today?
AB  - When measured by the number of medicines consumed or prescriptions written, the
      topical and transdermal routes of drug delivery pale into insignificance compared
      with oral therapy. Industrial colleagues, therefore, occasionally adopt a
      somewhat utilitarian stance and question the value of academic research into skin
      treatment and drug permeation, with the rather parochial argument that it is of
      limited use to the UK pharmaceutical industry. To consider the validity of this
      somewhat dismissive approach, which in its extreme form essentially regards
      universities as servants of industry, we can consider the worldwide position with
      respect to commercial activity in dermatologicals and patches. We can then look
      at the intellectual challenges that make transdermal research so demanding (a
      prime role of universities is to seek out and tackle the difficult problems and,
      particularly, to pose such challenges to their PhD students). In skin research,
      it is essential that investigators apply fundamental physicochemical principles
      to an extremely variable and complex biological tissue. The work discussed here
      provides avenues for further research.

PMID- 11576857
TI  - New drug leaves cancer cells gasping for air.

PMID- 11576858
TI  - Depleting cholesterol to make sex safer.

PMID- 11576859
TI  - New option for reversible suppression of menstruation.

PMID- 11576862
TI  - Private prescription: Science with a smile - more limericks.

PMID- 11576863
TI  - A thermodynamic exploration into pharmaceutical drug solubility.

PMID- 11576864
TI  - Straightening out DNA replication - molecular combing.

PMID- 11576865
TI  - Rational drug discovery revisited: interfacing experimental programs with bio-
      and chemo-informatics.
AB  - Over the past few years, bio- and chemo-informatics have rapidly evolved as
      related yet distinct disciplines. In drug discovery, it is increasingly
      recognized that combining and integrating these approaches is crucial for their
      successful application. In addition, the use of complementary experimental and
      informatics techniques increases the chances of success in many stages of the
      discovery process, from the identification of novel targets and elucidation of
      their functions to the discovery and development of lead compounds with desired
      properties. This review highlights recent trends that emphasize the role of
      integrated bio- and chemo-informatics research in drug discovery and discusses
      representative concepts and methodologies.

PMID- 11576866
TI  - Recent developments in computational proteomics.
AB  - The mapping of the human genome was completed earlier this year and efforts are
      underway to understand the role of gene products (i.e. proteins) in biological
      pathways and human disease and to exploit their functional roles to derive
      protein therapeutics and protein-based drugs. A key component to the next
      revolution in the 'post-genomic' era will be the increasingly widespread use of
      protein structure in rational experimental design. Improvements in quality,
      availability and utility of large-scale three- and four-dimensional protein
      structural information are enabling a revolution in rational design, having
      particular impact on drug discovery and optimization. New computational
      methodologies now yield modeled structures that are, in many cases,
      quantitatively comparable with crystal structures, at a fraction of the cost.

PMID- 11576867
TI  - Tumor angiogenesis as a therapeutic target.
AB  - Angiogenesis - the formation of new blood vessels within a tumor (or many other
      tissue types) - has become a hotbed of pharmacological research as well as
      industrial drug discovery. This is the result of the efforts of a generation of
      scientists elucidating the complex (patho)physiological, biochemical and
      molecular events accompanying angiogenesis. It is estimated that >300 drug
      candidates are currently in various stages of testing, and it is, therefore,
      impossible to capture all of this in a brief review. Therefore, the emphasis here
      is on relatively advanced projects that are either in preclinical or clinical
      development, thus neglecting, to a large extent, the many exciting avenues being
      pursued in both academic and biotechnology laboratories. Although the potential
      of the approaches described cannot be overestimated, it is also important to note
      that there is still no drug on the market that achieves clinical benefit based on
      a selective modulation or inhibition of angiogenesis.

PMID- 11576869
TI  - System for time and/or site-specific oral drug delivery.

PMID- 11576868
TI  - Monitor: molecules and profiles.

PMID- 11576870
TI  - Erratum.

PMID- 11576871
TI  - Enzymes inside lipid vesicles: preparation, reactivity and applications.
AB  - There are a number of methods that can be used for the preparation of enzyme
      containing lipid vesicles (liposomes) which are lipid dispersions that contain
      water-soluble enzymes in the trapped aqueous space. This has been shown by many
      investigations carried out with a variety of enzymes. A review of these studies
      is given and some of the main results are summarized. With respect to the vesicle
      forming amphiphiles used, most preparations are based on phosphatidylcholine,
      either the natural mixtures obtained from soybean or egg yolk, or chemically
      defined compounds, such as DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) or
      POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine). Charged enzyme
      containing lipid vesicles are often prepared by adding a certain amount of a
      negatively charged amphiphile (typically dicetylphosphate) or a positively
      charged lipid (usually stearylamine). The presence of charges in the vesicle
      membrane may lead to an adsorption of the enzyme onto the interior or exterior
      site of the vesicle bilayers. If (i) the high enzyme encapsulation efficiencies;
      (ii) avoidance of the use of organic solvents during the entrapment procedure;
      (iii) relatively monodisperse spherical vesicles of about 100 nm diameter; and
      (iv) a high degree of unilamellarity are required, then the use of the so-called
      'dehydration-rehydration method', followed by the 'extrusion technique' has shown
      to be superior over other procedures. In addition to many investigations in the
      field of cheese production--there are several studies on the (potential) medical
      and biomedical applications of enzyme-containing lipid vesicles (e.g. in the
      enzyme-replacement therapy or for immunoassays)--including a few in vivo studies.
      In many cases, the enzyme molecules are expected to be released from the vesicles
      at the target site, and the vesicles in these cases serve as the carrier system.
      For (potential) medical applications as enzyme carriers in the blood circulation,
      the preparation of sterically stabilized lipid vesicles has proven to be
      advantageous. Regarding the use of enzyme-containing vesicles as submicrometer
      sized nanoreactors, substrates are added to the bulk phase. Upon permeation
      across the vesicle bilayer(s), the trapped enzymes inside the vesicles catalyze
      the conversion of the substrate molecules into products. Using physical (e.g.
      microwave irradiation) or chemical methods (e.g. addition of micelle-forming
      amphiphiles at sublytic concentration), the bilayer permeability can be
      controlled to a certain extent. A detailed molecular understanding of these
      (usually) submicrometer-sized bioreactor systems is still not there. There are
      only a few approaches towards a deeper understanding and modeling of the
      catalytic activity of the entrapped enzyme molecules upon externally added
      substrates. Using micrometer-sized vesicles (so-called 'giant vesicles') as
      simple models for the lipidic matrix of biological cells, enzyme molecules can be
      microinjected inside individual target vesicles, and the corresponding enzymatic
      reaction can be monitored by fluorescence microscopy using appropriate
      fluorogenic substrate molecules.

PMID- 11576872
TI  - Zinc-mediated thermal stabilization of carboxypeptidase A.
AB  - In this study we investigated the contribution of Zn ions to the catalytic and
      structural thermostability of carboxypeptidase A (CPA). Structural studies on CPA
      molecule, performed in the presence of a number of ligands, demonstrated the
      multiple binding models around Zn ions which may affect the enzyme functions.
      Zinc was reported to bind at various sites in the CPA molecule at room
      temperature leading to inhibition of its enzymic activity. In this study we found
      that binding of Zn to CPA molecule followed by exposure to 50 degrees C did not
      inhibit the enzymic activity but activates and protects it against heat
      denaturation. The stabilization effect was found to be dependent on the
      increasing Zn/CPA ratios. The moderate changes of CPA activity as well as the UV
      and fluorescence spectra analyses indicate that the main function of the newly
      introduced zinc atoms is structural rather than catalytical.

PMID- 11576873
TI  - Methylation of episomal plasmids as a barrier to transient gene expression via a
      synthetic delivery vector.
AB  - Efficient and sustained transgene expression are desirable features for many
      envisioned gene therapy applications, yet synthetic vectors tested to date are
      rarely successful in achieving these properties. Substantial research efforts
      have focused on protection of plasmid DNA from nuclease attack as well as
      increasing nuclear transport of plasmids, resulting in significant but still
      limited gains. We show here that a further barrier to efficient and sustained
      expression exists for synthetic vectors: plasmid DNA methylation. We have
      investigated this barrier for transient expression of a green fluorescent protein
      (GFP) transgene delivered via Lipofectamine, by testing the effects of culturing
      C3A human hepatoblastoma cells with 5-Azacytidine (AzaC), an irreversible
      inhibitor of DNA methyltransferase. To control for loss of plasmids by dilution
      during mitosis, transfected cells were growth-arrested for 1 week and their
      subsequent GFP expression quantified by FACS. In the presence of AzaC, a
      significantly greater fraction of transfected cells remained GFP-positive and
      possessed higher levels of GFP production relative to AzaC-untreated cells.
      Additionally, we have applied a Methyl-Assisted PCR (MAP) assay to quantify a
      subset of methylated CpG sites in the GFP gene. When MAP was performed on
      plasmids isolated from transfected cells, the extent of methylation was found to
      be inversely related to the level of GFP expression.

PMID- 11576874
TI  - Use of base in the treatment of severe acidemic states.
AB  - Severe acidemia (blood pH < 7.1 to 7.2) suppresses myocardial contractility,
      predisposes to cardiac arrhythmias, causes venoconstriction, and can decrease
      total peripheral vascular resistance and blood pressure, reduce hepatic blood
      flow, and impair oxygen delivery. These alterations in organ function can
      contribute to increased morbidity and mortality. Although it seemed logical to
      administer sodium bicarbonate to attenuate acidemia and therefore lessen the
      impact on cardiac function, the routine use of bicarbonate in the treatment of
      the most common causes of severe acidemia, diabetic ketoacidosis, lactic
      acidosis, and cardiac arrest, has been an issue of great controversy. Studies of
      animals and patients with these disorders have reported conflicting data on the
      benefits of bicarbonate, showing both beneficial and detrimental effects.
      Alternative alkalinizing agents, tris-hydroxymethyl aminomethane and Carbicarb,
      have shown some promise in studies of animals and humans, and reevaluation of
      these buffers in the treatment of severe acidemic states seems warranted. The
      potential value of base therapy in the treatment of severe acidemia remains an
      important issue, and further studies are required to determine which patients
      should be administered base therapy and what base should be used.

PMID- 11576875
TI  - Predicting progression in IgA nephropathy.
AB  - Immunoglobulin A (IgA) nephropathy is one of the most common primary types of
      glomerulonephritis to progress to end-stage renal disease. Its variable and often
      long natural history makes it difficult to predict outcome. We investigated the
      association of the rate of renal function decline based on the slope of
      creatinine clearance over time with demographic, clinical, laboratory, and
      histological data from 298 patients with biopsy-proven IgA nephropathy with a
      mean follow-up of 70 months. Using univariate analysis, urinary protein excretion
      at baseline and Lee pathological grading, as well as mean arterial pressure (MAP)
      and urinary protein excretion during follow-up, were associated with the rate of
      deterioration in renal function. Of these, only MAP and urinary protein excretion
      during follow-up were identified as independent factors by multiple linear
      regression analysis. The combination of best accuracy of prediction and shortest
      observation time using these two parameters was reached between the second and
      third years of follow-up. A semiquantitative method of estimating the rate of
      progression by using these factors was developed. These results indicate that MAP
      and severity of proteinuria over time are the most important prognostic
      indicators of IgA nephropathy. The potential relevance of the algorithm in
      patient management is shown.

PMID- 11576876
TI  - Tonsillectomy and steroid pulse therapy significantly impact on clinical
      remission in patients with IgA nephropathy.
AB  - We conducted a retrospective investigation of renal outcome in 329 patients with
      immunoglobulin A (IgA) nephropathy with an observation period longer than 36
      months (82.3 +/- 38.2 months) in our renal unit between 1977 and 1995. Clinical
      remission, renal progression, and the impact of covariates were estimated by
      Kaplan-Meier analysis and a Cox regression model. In 157 of 329 patients (48%),
      disappearance of urinary abnormalities (clinical remission) was obtained. None of
      these 157 patients showed progressive deterioration, defined as a 50% increase in
      serum creatinine (Scr) level from baseline, during the observation period.
      Conversely, in patients without clinical remission, the Kaplan-Meier estimate of
      probability of progressive deterioration was 21% +/- 5% at 10 years. In the
      multivariate Cox regression model with 13 independent covariates, initial Scr
      level, histological score, tonsillectomy, and high-dose methylprednisolone
      therapy had a significant impact on clinical remission, whereas proteinuria, age,
      sex, levels of hematuria, blood pressure, conventional steroid therapy,
      angiotensin-converting enzyme inhibitor therapy, and cyclophosphamide therapy had
      no significant effect. These findings indicate that interventions aimed at
      achieving clinical remission have provided encouraging results applicable to
      managing patients with IgA nephropathy.

PMID- 11576877
TI  - Comparison of cross-sectional renal function measurements in African Americans
      with hypertensive nephrosclerosis and of primary formulas to estimate glomerular
      filtration rate.
AB  - Renal function measurements were obtained in 1,703 African Americans with
      presumed hypertensive nephrosclerosis who were screened for entry into the
      African-American Study of Hypertension and Kidney Disease (AASK). We examined the
      effect of race on relationships involving renal variables by comparing African
      Americans enrolled into the AASK with non-African Americans enrolled into the
      Modification of Diet in Renal Disease (MDRD) study. We examined the effect of
      gender on renal variables by comparing African American men and women. We
      compared various methods for estimating glomerular filtration rate (GFR) with
      iodine 125-labeled ((125)I)-iothalamate GFR. AASK data were also used to derive a
      new formula for estimating GFR in African Americans. After adjusting for age,
      sex, and baseline GFR, African American patients on the AASK study were heavier
      and had larger body surface areas and body mass indices than either MDRD African
      Americans or non-African Americans. African Americans had greater serum
      creatinine levels and urinary creatinine excretions for any given level of GFR.
      Mean GFR was greater in African American men than African American women (59.7
      versus 51.7 mL/min/1.73 m(2)), although serum creatinine levels were also greater
      in men (1.91 versus 1.73 mg/dL). Seventy-eight percent of women with serum
      creatinine levels between 1.2 and 1.5 mg/dL had GFRs less than 65 mL/min/1.73
      m(2). For African Americans in the AASK, GFR was overestimated by the 24-hour
      creatinine clearance and underestimated by the Cockcroft-Gault formula. A
      prediction formula developed in the MDRD study more accurately predicted GFR in
      AASK patients than these measurements. AASK data were also used to derive a new
      five-term formula for estimating GFR that was slightly more accurate in the
      African Americans in the AASK than the MDRD formula (median percentage of error,
      12.4% for the MDRD formula versus 12.1% for the AASK formula). Important
      differences exist in renal variables between African Americans and non-African
      Americans and between African American men and African American women. Formulas
      using demographic data and readily measured serum values estimate (125)I
      iothalamate GFR.

PMID- 11576878
TI  - Long-term treatment of focal segmental glomerulosclerosis in children with
      cyclosporine given as a single daily dose.
AB  - Cyclosporine (CsA) has been successfully used for treatment of children with
      focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome (NS) for the
      last decade. Response rates of 50% to 100% have been reported using twice-daily
      dosing of 5 to 32 mg/kg/d, achieving trough blood levels of 70 to 500 ng/mL.
      Treatment has been associated with a high incidence of side effects, including
      nephrotoxicity, hypertension, gingival hyperplasia, and hirsutism. To determine
      whether once-daily low-dose CsA could minimize side effects and still induce
      remission, 21 children with biopsy-proven FSGS and NS, each treated with CsA, 4.6
      +/- 0.8 mg/kg/d, with no predetermined target trough blood levels, were studied.
      Eleven of 21 children (52%) attained complete remission and 5 of 21 children
      (24%) attained partial remission, for a total response rate of 76%. Mean time to
      response was 2.8 +/- 0.8 months, and mean duration of therapy was 20.6 +/- 13.7
      months. CsA dosage was tapered or stopped in 9 responders; 3 of these patients
      maintained remission at last follow-up 6 to 13 months later, and 6 patients
      relapsed at 1.5 to 18.7 months (mean, 8.7 months). Five of these 6 patients
      responded again when CsA therapy was restarted or the dosage was increased.
      Twelve of 16 responders were still being administered CsA at last follow-up 11 to
      60 months (mean, 24.6 months) later. Five of 21 patients (24%) had no response to
      CsA during 2 to 27 months of therapy; 4 of these 5 patients developed end-stage
      renal disease after CsA therapy was stopped. Side effects of CsA therapy were
      minimal: 1 patient each developed new-onset hypertension or gingival hyperplasia,
      and no patient had hirsutism or nephrotoxicity. Single daily low-dose CsA appears
      to be effective for long-term treatment of children with FSGS and NS, with fewer
      side effects than twice-daily dosing.

PMID- 11576879
TI  - Tubular phenotypic change in progressive tubulointerstitial fibrosis in human
      glomerulonephritis.
AB  - There is much debate over the origins of fibroblast-type cells that accumulate in
      interstitial fibrosis. A controversial hypothesis, supported by data from animal
      and cell-culture studies, is that fibroblast-type cells can derive from tubular
      epithelial cells by a process of epithelial-mesenchymal transdifferentiation.
      However, to date, no evidence supports this postulate in human
      glomerulonephritis. This study sought to provide evidence that tubular epithelial
      cells can undergo phenotypic change toward a fibroblast-like cell in human
      glomerulonephritis. One hundred twenty-seven open renal biopsy specimens from
      patients with minimal change disease (MCD), immunoglobulin A (IgA) nephropathy,
      and rapidly progressive glomerulonephritis (RPGN) were examined for tubular
      phenotypic change by two-color immunohistochemistry using the criteria of de novo
      expression of alpha-smooth muscle actin (alpha-SMA), a myofibroblast marker; loss
      of the epithelial marker cytokeratin; and collagen production. In normal human
      kidney and MCD, tubular epithelial cells expressed cytokeratin with no evidence
      of alpha-SMA staining. However, in 36 of 90 cases of IgA nephropathy and 9 of 18
      cases of RPGN, small numbers of tubular epithelial cells in areas of fibrosis
      showed de novo alpha-SMA expression, accounting for 0.4% +/- 0.2% (IgA
      nephropathy) and 3.8% +/- 1.5% (RPGN) of cortical tubules. An intermediate stage
      of phenotypic change was observed in some cuboidal epithelial cells that
      expressed both cytokeratin and alpha-SMA. Tubules containing alpha-SMA-positive
      (alpha-SMA(+)) cells also stained for collagen types I and III, suggesting that
      tubular cells undergoing phenotypic change have an active role in the fibrotic
      process. There also was a marked increase in transforming growth factor-beta1
      (TGF-beta1) tubular expression in areas with interstitial fibrosis, including
      tubules with phenotypic change. There was a highly significant correlation
      between tubular alpha-SMA expression and interstitial fibrosis, interstitial
      alpha-SMA(+) myofibroblast accumulation, deposition of collagen types I and III,
      tubular TGF-beta1 expression, and renal dysfunction. In conclusion, this study
      provides evidence that tubular epithelial cells can undergo phenotypic change
      toward a myofibroblast-like phenotype on the basis of de novo alpha-SMA
      expression, loss of cytokeratin, and de novo collagen staining. These data,
      although not conclusive, provide the first support for the hypothesis that
      transdifferentiation of tubular epithelial cells has a role in progressive renal
      fibrosis in human glomerulonephritis.

PMID- 11576880
TI  - Familial clustering of ruptured intracranial aneurysms in autosomal dominant
      polycystic kidney disease.
AB  - Ruptured intracranial aneurysm (RICA) is a life-threatening complication of
      autosomal dominant polycystic kidney disease (ADPKD). A family history of RICA
      may be a risk factor for RICA. Six hundred eight adult members of 199 ADPKD
      families were interviewed, and family pedigrees were constructed. Individuals
      were classified as having definite, probable, or possible RICAs from evidence and
      history obtained in interviews. Central nervous system (CNS) events not
      consistent with RICA were classified as other CNS events. Seventy-seven CNS
      events occurred in 906 subjects with ADPKD (8.5%) versus 13 events in 823
      subjects without ADPKD (1.6%; P < 0.0001). No event in subjects without ADPKD was
      consistent with an RICA. Twenty-seven other (non-RICA) CNS events occurred in
      subjects with ADPKD (3%) versus 13 events in subjects without ADPKD (1.6%; P =
      0.05). The frequency of RICA was increased in subjects with ADPKD: 21 definite
      RICAs in subjects with ADPKD (2%) versus none in subjects without ADPKD (P <
      0.001); 28 definite and probable RICAs in subjects with ADPKD (3%) versus none in
      subjects without ADPKD (P < 0.001); and 50 definite, probable, and possible RICAs
      in subjects with ADPKD (5.5%) versus none in subjects without ADPKD (P < 0.001).
      The null hypothesis that RICAs are randomly distributed among subjects with ADPKD
      was tested for definite RICAs (n = 21), definite and probable RICAs (n = 28), and
      definite, probable, and possible RICAs (n = 50). In the three categories, the
      null hypothesis was rejected at P less than 0.05, P less than 0.05, and P less
      than 0.005, respectively. Vascular CNS events occurred more frequently in ADPKD
      than non-ADPKD family members, and clustering of RICAs occurred in families with
      ADPKD.

PMID- 11576881
TI  - Survival after end-stage renal disease in autosomal dominant polycystic kidney
      disease: contribution of extrarenal complications to mortality.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) accounts for 8% to 10% of
      patients with end-stage renal disease (ESRD) in the United States and Europe.
      Progressive expansion of multiple bilateral renal cysts leads to massive
      enlargement of the kidneys and progressive renal failure. Extrarenal
      manifestations of ADPKD, such as liver cysts, intracranial aneurysms, cardiac
      valvular disease, and perhaps diverticulosis, have been documented extensively in
      cross-sectional studies, but little is known about their natural history. It is
      thought that extrarenal aspects of ADPKD contribute to increased mortality, yet
      survival on dialysis of the ADPKD population surpasses that of the general
      dialysis population. To address this issue, we analyzed the relative risk and
      causes of death after ESRD in ADPKD versus nondiabetic controls using data from
      the United States Renal Data System. Relative risk of death from any cause,
      including the major extrarenal manifestations of ADPKD, was determined as a
      function of ESRD treatment modality (dialysis or transplantation). We found a
      lower total mortality rate in ADPKD ESRD patients compared with nondiabetic
      control ESRD patients (relative risk of death in ADPKD = 0.57; P < 0.001).
      Mortality rates of extrarenal complications except for polycystic liver disease
      were similar or lower in ADPKD patients than in nondiabetic controls. Mortality
      secondary to extrarenal complications was substantially lower than that secondary
      to cardiovascular or cerebrovascular disease.

PMID- 11576882
TI  - N(epsilon)-(carboxymethyl)lysine levels in patients with type 2 diabetes: role of
      renal function.
AB  - Advanced glycation end products (AGEs) such as N(epsilon)-(carboxymethyl)lysine
      (CML) have been implicated in the development and progression of diabetic
      nephropathy. The aim of the present study is to investigate AGE levels in
      patients with type 2 diabetes with special regard to the role of renal
      impairment. Serum and urine CML levels (using a newly developed enzyme-linked
      immunosorbent assay), as well as serum AGE-fluorescence, were measured in 109
      patients with type 2 diabetes. Patients were divided into groups with normal and
      impaired renal function. We found elevated serum fluorescent AGE and CML levels,
      as well as decreased urinary CML excretion rates, in patients with diabetes with
      renal impairment, but not those with normal renal function. In the presence of
      impaired renal function, serum CML and fluorescent AGE levels showed a
      significant inverse relation with creatinine clearance and a significant direct
      correlation with each other. No relationship could be found between serum AGE
      levels and parameters of blood glucose control or the presence of the following
      clinical complications: ischemic heart disease, diabetic retinopathy, and
      neuropathy. We conclude that the decline in renal function leads to increased
      serum AGE levels in patients with type 2 diabetes.

PMID- 11576883
TI  - A placebo-controlled trial to evaluate immunomodulatory effects of paricalcitol.
AB  - Calcitriol has shown a benefit in various small uncontrolled studies of ex vivo
      immune function. We hypothesized that paricalcitol, a new vitamin D derivative,
      will have a positive effect on the immune system with minimal adverse effects on
      calcium homeostasis. Thirty-one hemodialysis patients not administered vitamin D
      because of low intact parathyroid hormone (PTH) levels were randomized to placebo
      or 4 microg of paricalcitol intravenously with the hemodialysis session three
      times weekly for 12 weeks. Effects on in vivo and ex vivo assessments of immune
      function were evaluated. All patients achieved the target dose of paricalcitol.
      Twenty patients were anergic at the start of the study; 4 of 11 patients in the
      paricalcitol group and 0 of 9 patients in the placebo group converted to reactive
      (P = 0.09). The in vivo response to standard hepatitis B booster vaccine and in
      vitro proliferation and release of interleukin-2 (IL-2), IL-6, tumor necrosis
      factor-alpha, and interferon-gamma from stimulated lymphocytes were not different
      between the groups. In contrast to clinical immune effects, paricalcitol
      increased serum calcium levels and decreased PTH and bone alkaline phosphatase
      levels (all P < 0.05). However, hypercalcemia was infrequent. In vitro
      experiments showed that paricalcitol led to greater dose-dependent thymidine
      uptake than calcitriol in lymphocytes isolated from either dialysis patients or
      control subjects. Paricalcitol has a tendency toward improving delayed
      hypersensitivity reactions, but did not have other proimmune effects. However, as
      expected, paricalcitol had significant effects on calcium homeostasis compared
      with placebo. Thus, patients with low PTH levels are unlikely to experience the
      proimmune effects of vitamin D therapy without more profound and potentially
      adverse oversuppression of PTH.

PMID- 11576884
TI  - Anemia: an early complication of chronic renal insufficiency.
AB  - The strong association between anemia and cardiovascular complications among
      patients with end-stage renal disease suggests that anemia during chronic renal
      insufficiency (CRI) may also have important consequences. We performed a
      retrospective cohort study to identify factors associated with severe anemia
      (hematocrit [Hct] < 30%) and examine anemia management practices in CRI. The CRI
      cohort was composed of 604 adult patients with elevated serum creatinine levels.
      There was a direct correlation between predicted glomerular filtration rate and
      Hct (r = 0.49) and an inverse correlation between serum creatinine level and Hct
      (r = -0.37). Anemia was noted early in CRI; 45% of patients with serum creatinine
      levels of 2 mg/dL or less had an Hct less than 36%, and 8% had an Hct less than
      30%. During the course of the study, mean Hct decreased from 35.1% +/- 5.6% to
      31.8% +/- 5.6%. Iron studies were obtained in only 19% of patients, and among
      these, the prevalence of iron deficiency (transferrin saturation < 20%) was 54%.
      Only 30% and 26% of patients were administered recombinant human erythropoietin
      (rHuEPO) and iron, respectively. Multivariate analyses showed that diabetes as
      the cause of renal disease, greater serum creatinine level, and having a single
      nephrology visit were associated with greater odds for the presence of anemia. A
      lower Hct and having a single nephrology visit were associated with greater odds
      for rHuEPO use. These results show that anemia begins early in the course of CRI,
      and management of anemia is suboptimal, even among patients under the care of
      nephrologists. Educational programs to optimize anemia management among patients
      with CRI are needed.

PMID- 11576885
TI  - Duration of dialysis and its relationship to dialysis adequacy, anemia
      management, and serum albumin level.
AB  - An analysis of the relationship between intermediate outcomes and duration of
      dialysis therapy in hemodialysis patients was performed by linking Health Care
      Financing Administration (HCFA) Core Indicators data with data obtained from HCFA
      form 2728 at the initiation of dialysis therapy. Patients who recently initiated
      hemodialysis therapy were less likely to meet Dialysis Outcomes Quality
      Initiative guidelines than patients with a longer duration of dialysis therapy.
      For both urea reduction ratio and Kt/V, odds ratios for adequate dialysis were
      approximately 0.20 for a duration of dialysis therapy less than 0.5 years and
      0.42 to 0.63 for a duration of dialysis therapy of 0.5 to 1.0 years compared with
      a duration of dialysis therapy of 2.0 years or greater. For patients with a
      duration of dialysis therapy less than 0.5 years (compared with >/=2.0 years),
      the odds ratio for a hematocrit less than 28% was approximately 3.0, that for a
      hematocrit 33% or greater was approximately 0.6, and that for a serum albumin
      level of 3.5 g/dL or greater (bromcresol green method) or 3.2 g/dL or greater
      (bromcresol purple method) was approximately 0.4. There was a direct relationship
      between glomerular filtration rate at the initiation of dialysis therapy and both
      serum albumin and hematocrit values. Patients administered recombinant human
      erythropoietin (rHuEPO) predialysis were more likely to have greater hematocrits.
      There also was a direct relationship between hematocrit and serum albumin level.
      Therefore, several actionable items in regard to attentive overall medical care
      can result in an improvement in the percentage of patients newly started on
      hemodialysis therapy who meet intermediate outcomes, including the administration
      of rHuEPO predialysis, correction of iron deficiency, and timely placement of a
      permanent dialysis access.

PMID- 11576886
TI  - Extent and sources of geographic variation in Medicare end-stage renal disease
      expenditures.
AB  - Geographic variations in practices and expenditures have been widely documented,
      leading to concerns that care in some regions is clinically suboptimal and/or
      economically inefficient. Our objectives are to determine the extent and sources
      of geographic variation in Medicare expenditures per patient with end-stage renal
      disease (ESRD) per year. The study population included all patients with ESRD
      with Medicare as primary payer during 1997 (n = 284,670). Medicare expenditures
      were summarized at the hospital referral region (HRR) level. Using regression
      analysis, we estimated the relationship between expenditures and demographics,
      case mix, dialysis provider characteristics, distribution of patients across
      renal replacement therapy modalities, standardized hospitalization ratios, and
      healthcare wages. Spending per patient-year varied threefold across HRRs, ranging
      from $17,791 to $59,025 (mean, $38,966 +/- $6,774 [SD]). The regression equation
      explained 80% of this variation. Although several demographic and case-mix
      indicators that have been related to spending at the individual level were
      statistically significant predictors of spending at the HRR level, they did not
      show enough geographic variation to explain a large fraction of spending
      variation. Rather, patient distributions across renal replacement modalities,
      hospitalization patterns, and healthcare wages were the most powerful predictors
      of spending. Compared with Medicare generally, both the mean and SD of ESRD
      expenditures were approximately seven times larger. The substantial geographic
      variability in expenditures for patients with ESRD indicates the potential for
      improving efficiency and quality of care. Interventions designed to increase
      transplantation rates, ensure access to peritoneal dialysis, and reduce
      hospitalization appear most promising.

PMID- 11576887
TI  - Role of bioimpedance spectroscopy in assessment of body water compartments in
      hemodialysis patients.
AB  - Bioimpedance spectroscopy (BIS) has been advocated as a tool to assess fluid
      status in hemodialysis (HD) patients. However, uncertainty remains about the
      reliability of BIS in patients with abnormalities in fluid status. Aims of the
      study are to assess the agreement between total-body water (TBW) and
      extracellular volume (ECW) measured by BIS and tracer dilution (deuterium oxide
      [D(2)O] and sodium bromide [NaBr]), the influence of the relative magnitude of
      water compartments (expressed as TBW(D(2)O) and ECW(NaBr):body weight) on the
      agreement between BIS and tracer dilution, and the ability of BIS to predict
      acute changes in fluid status. BIS and tracer dilution techniques were performed
      in 17 HD patients before a dialysis session. Moreover, the relation between BIS
      and gravimetric weight changes was assessed during both isolated ultrafiltration
      and HD. Correlation coefficients between TBW and ECW measured by BIS and tracer
      dilution were r = 0.71 and r = 0.71, respectively. Mean differences (tracer-BIS)
      were 6.9 L (limits of agreement, -1.5 to 21.6 L) for TBW and 2.3 L (limits of
      agreement, -1.7 to 9.7 L) for ECW. There was a significant relationship between
      the relative magnitude of TBW and ECW compartments and disagreement between BIS
      and tracer dilution (r = 0.65 and r = 0.77; P < 0.05). During both isolated
      ultrafiltration and HD, there was a significant relation between gravimetric
      changes and change in ECW(BIS) (r = 0.83 and r = 0.76; P < 0.05), but not with
      change in TBW(BIS). In conclusion, agreement between BIS and tracer dilution
      techniques in the assessment of TBW and ECW in HD patients is unsatisfactory. The
      discrepancy between BIS and dilution techniques is related to the relative
      magnitude of body water compartments. Nevertheless, BIS adequately predicted
      acute changes in ECW during isolated ultrafiltration and HD, in contrast to
      changes in TBW.

PMID- 11576888
TI  - Depression and marital dissatisfaction in patients with end-stage renal disease
      and in their spouses.
AB  - Little research has been performed assessing patients with end-stage renal
      disease (ESRD) as parts of marital dyads or within family structures. Recent
      findings suggest patient interactions within such systems are associated with
      patient outcomes. To evaluate the relationship between level of patient
      depression and spouse psychosocial status, 55 couples in which one partner was
      undergoing chronic hemodialysis therapy for ESRD were interviewed. Two variables
      that alone and in interaction with one another were expected to relate to the
      spouse's level of depression and marital satisfaction were investigated: patient
      depression level and spouse's perceived social support. Depression was assessed
      using the Beck Depression Inventory (BDI). Spouses' levels of depressive affect
      correlated directly with patient BDI scores. A significant two-way interaction
      for spousal depression (patient depression and spousal support) supported viewing
      spouses' adjustment as a function of the interaction between spouse and patient
      factors. Additionally, a main effect of perceived spousal social support on
      spousal marital satisfaction indicated that spouses reporting high levels of
      social support had the least marital strain. The severity of the patient's
      illness did not correlate with any of the predictor variables or measures of
      spousal adjustment, but spouses reported significantly lower functional status
      for patients than did nephrologists. Spouse and patient levels of depression are
      related, although causal relationships cannot be determined by these studies.
      Moreover, spouse perception of marital satisfaction is related to depression
      scores. These findings suggest the patient with ESRD functions in a psychosocial
      dyad. Spouse psychosocial status could impact on the level of patient depression,
      and the spouse might be amenable to interventions that could improve patient
      outcome.

PMID- 11576889
TI  - Attitudes of patients toward cardiopulmonary resuscitation in the dialysis unit.
AB  - Some dialysis units have a policy of performing cardiopulmonary resuscitation
      (CPR) on all patients who experience cardiac arrest while undergoing dialysis.
      However, to perform CPR on patients who do not want it is contrary to ethics and
      the law. We interviewed hemodialysis patients in 12 units in Missouri, New York,
      and West Virginia to learn their attitudes about CPR. Four hundred sixty-nine of
      830 patients (57%) agreed to be interviewed. Eighty-seven percent of patients
      wanted to undergo CPR if cardiac arrest were to occur while undergoing dialysis.
      Patients who had seen CPR on television were more likely to report that they knew
      what CPR was (94% versus 68%; P < 0.001) and to want CPR (88% versus 78%; P =
      0.033). Thirteen percent of patients did not want CPR if cardiac arrest were to
      occur while undergoing dialysis. Compared with patients who wanted CPR, those who
      did not were older (69 versus 59 years; P = 0.026), had more comorbid conditions
      (2.0 versus 1.5 comorbid conditions; P = 0.016), and were more likely to have a
      living will (61% versus 43%; P = 0.01), be widowed (36% versus 20%; P = 0.026),
      and live in a nursing home (9% versus 3%; P = 0.017). Blacks were significantly
      more likely to want CPR than whites (adjusted odds ratio, 6.56; 95% confidence
      interval, 2.57 to 22.27). Only 20 of 58 patients (35%) who did not want CPR were
      certain they had a do-not-resuscitate order in their dialysis chart. Ninety-two
      percent of patients who wanted CPR agreed that patients who did not want CPR
      should have their wishes respected by the dialysis unit. We conclude that most
      dialysis patients want to undergo CPR, but also want other patients' preferences
      not to be resuscitated to be respected. Dialysis units need to do a better job of
      identifying patients who prefer not to be resuscitated and respecting their
      wishes in the event of cardiac arrest while undergoing dialysis. Most
      importantly, nephrologists and dialysis unit staff need to educate dialysis
      patients about the poor outcomes with CPR so that dialysis patients' decisions
      about CPR are informed.

PMID- 11576890
TI  - Buzz in the axilla: a new physical sign in hemodialysis forearm graft evaluation.
AB  - The value of physical signs in predicting flow rates or polytetrafluoroethylene
      (PTFE) hemodialysis graft survival is not well known. Simultaneous physical
      examination and flow measurements were performed in 67 dialysis patients with
      PTFE grafts over a period of 1 month. Physical signs included the presence and
      location of a palpable thrill, location and auscultatory nature of the bruit, and
      presence or absence of a pulsation. Patients were followed up for 1 year to
      detect the time to failure defined by angioplasty, clotting, or surgical
      revision. There was a fair correlation between physical signs and graft flow
      rates. In a multivariate model, systolic blood pressure, location of the thrill,
      and patient age were the best predictors of graft flow. During follow-up, there
      were 68 graft failures (30 grafts, angioplasty alone; 38 grafts, thrombosis
      followed by interventional or surgical revisions). The median survival of a graft
      without a thrill in the axilla was 154 days compared with 321 days when a thrill
      was present (P = 0.05, log-rank test). Dialysis graft physical examination is a
      useful test to predict graft flows, as well as graft failure. The single best
      test is the location of the thrill along the venous limb of the graft. Average
      flow rates for no thrill, thrill but distal to the midarm, and axillary buzz were
      approximately 500, 750, and 1,000 mL/min, respectively. This single physical sign
      also correlated with subsequent graft failure and should be incorporated into
      physical examinations of all dialysis grafts.

PMID- 11576891
TI  - A scanning electron microscopy analysis of a spontaneous hemodialysis catheter
      fracture.
AB  - Central venous catheters have become increasingly important in hemodialysis
      treatment. With their increased use, catheter-related problems will be seen more
      frequently, and more rare complications may be observed. We describe the first
      case of asymptomatic spontaneous breakdown of a tunneled cuffed silicone catheter
      used for long-term hemodialysis treatment. This was discovered on removal of the
      catheter, leaving behind a catheter fragment in the left lower pulmonary lobe. An
      extensive scanning electron microscopy study showed accumulation of lumps of
      nonsilicone material at the place of the fracture, leading to severe disruption
      of the original cross-linked elastomer structure. Using energy-dispersive X-ray
      spectral analysis, which shows all elements with an atomic number of 11 or
      greater in a material, we found the lumps were aggregates of barium sulfate
      particles used to visualize the catheter on fluoroscopy. We suggest that the use
      of too small or too many barium sulfate particles led to high viscosity of the
      raw silicone before polymerization, causing improper mixing of barium sulfate
      particles in the silicone matrix. This resulted in insufficient removal of
      admixed air bubbles and unequal dispersion of barium sulfate, with the potential
      for weak spots after extrusion of the silicone into its definitive shape. With
      the increasing use of hemodialysis catheters for prolonged periods, catheter
      related complications related to materials or manufacturing errors can be
      expected to occur more often.

PMID- 11576892
TI  - Creatinine excretion in continuous peritoneal dialysis: a systematic error of the
      Cockroft-Gault formula.
AB  - We investigated the hypothesis that the rate of loss of creatinine excretion with
      age in peritoneal dialysis (PD) patients differs from the rate predicted from the
      Cockroft-Gault formula (Cr(Pred)) by analyzing creatinine excretion data obtained
      from clearance studies of 925 patients on continuous ambulatory PD therapy with
      an age range of 12 to 91 years. Measured creatinine generation (Cr(Meas)) is the
      sum of creatinine excretion in urine plus dialysate (Cr(Excr)) plus an estimated
      metabolic degradation of creatinine. The effect of age on Cr(Excr) and the
      differences Cr(Excr) - Cr(Pred) and Cr(Meas) - Cr(Pred) were analyzed by linear
      regression. In 373 women, Cr(Excr) = W(16.9360 - 0.084A), r = -0.342, P < 0.001
      (where W is weight in kilograms and A is age in years). The regression slope was
      one half of the slope in the Cockroft-Gault formula. Cr(Excr) - Cr(Pred) = 
      413.91 + 4.78A, r = 0.300, P < 0.001. Cr(Meas) - Cr(Pred) = -176.36 + 4.37A, r =
      0.278, P < 0.001. In 552 men, Cr(Excr) = W(21.079 - 0.108A), r = -0.338, P <
      0.001. The regression slope was approximately one half of the slope in the
      Cockroft-Gault formula. Cr(Excr) - Cr(Pred) = -493.25 + 6.28A, r = 0.267, P <
      0.001. Cr(Meas) - Cr(Pred) = -66.41 + 3.63A, r = 0.143, P = 0.001. The rate of
      loss of creatinine excretion with age is one half of the rate predicted by the
      Cockroft-Gault formula in both women and men on PD therapy. Therefore, the
      difference between excretion (or measured generation) of creatinine and
      creatinine generation predicted by the Cockroft-Gault formula is not constant,
      but increases with age. The Cockroft-Gault formula systematically overestimates
      the effect of age on creatinine excretion in PD patients and is not suitable for
      predicting creatinine excretion in these subjects.

PMID- 11576893
TI  - Peritoneal dialysis fluids with a physiologic pH based on either lactate or
      bicarbonate buffer-effects on human mesothelial cells.
AB  - Conventional lactate (Lac)-buffered peritoneal dialysis (PD) solutions have
      turned out to be detrimental to human peritoneal cells, especially because of a
      low pH. In the present study, we focus on potential differences between Lac and
      bicarbonate (Bic) as a buffer when adjusted to a physiological pH. All test
      fluids were buffered with either 40 mmol/L of Lac or 34 mmol/L of Bic, sterile
      filtered, and adjusted to a pH of 7.4. Osmotic agents used were 1.36% glucose
      (Glu), 3.86% Glu, 1% amino acids (AA), and 7.5% Glu polymer (Glupoly). Human
      peritoneal mesothelial cells (HPMCs) were isolated from the omentum majus, grown
      to confluence, and incubated after the second passage for 15 minutes (37 degrees
      C and 5% carbon dioxide) with the test fluids. Cytotoxicity was controlled by
      measuring apoptotic and necrotic cells with cytofluorometry. Aerobic cell
      metabolism (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT]
      assay) and intracellular adenosine triphosphate (ATP) concentrations were
      measured to assess cell viability. Release of interleukin-6 (IL-6) from HPMCs was
      determined as a parameter of cellular host defense. No significant difference in
      apoptosis or necrosis rates was found between the solutions adjusted to normal
      pH. However, in the MTT assay, Bic solutions were superior to corresponding Lac
      pendants at an identical pH of 7.4 (P < 0.01). Intracellular ATP concentrations
      reflected a very similar pattern (P < 0.05). Glupoly in combination with Lac
      showed an impaired pattern with both the MTT and ATP assays. Regarding IL-1beta
      stimulated IL-6 release, there was a small, but not significantly better,
      response for Bic. Differences in manifest cell cytotoxicity reflected by
      apoptosis and necrosis rates could not be detected comparing PD solutions
      buffered with Lac or Bic at a physiological pH. However, distinct parameters of
      cell metabolism were superior with Bic compared with Lac. Especially Glupoly was
      inferior in combination with Lac as a buffer.

PMID- 11576894
TI  - Acute oxalate nephropathy induced by star fruit in rats.
AB  - In this study, we intend to establish a connection between star fruit and acute
      oxalate nephropathy and also investigate predisposing factors for its
      development. Male Sprague-Dawley rats of 180 to 200 g were assigned to four
      groups; namely, control, experimental, fasting, and water-deprivation groups. The
      former two groups were subjected to both fasting and water deprivation, whereas
      the latter two groups were subjected to either fasting or water deprivation,
      respectively. Except for tap water for controls, the remaining groups were
      administered 4 mL/100 g of body weight of sour star fruit juice with an oxalate
      concentration of 2.46 g/dL. After these procedures, serial measurement of serum
      creatinine levels and kidney pathological examination were performed. Peak serum
      creatinine levels in the control, experimental, fasting, and water-deprivation
      groups were 0.50 +/- 0.04, 1.46 +/- 0.26, 0.68 +/- 0.20, and 0.52 +/- 0.08 mg/dL,
      respectively. The experimental group had a greater peak serum creatinine level (P
      < 0.05). Mean serum creatinine levels of the experimental group days 0, 1, 2, 3,
      4, and 5 were 0.43 +/- 0.03, 1.11 +/- 0.18, 1.31 +/- 0.27, 1.16 +/- 0.28, 0.8 +/-
      0.26, and 0.82 +/- 0.28 mg/dL, respectively. Mean serum creatinine levels days 1
      to 3 were greater than that day 0 (P < 0.05). Pearson's correlation analysis of
      peak serum creatinine level and kidney weight for the experimental group showed a
      significant correlation (R = 0.75; P < 0.05; n = 9). In addition to typical
      changes of oxalate nephropathy, kidney pathological examination showed many
      refractile oxalate crystals with all rainbow colors under polarized light
      microscopy in the experimental group. In conclusion, sour star fruit with
      abundant oxalate contents could cause acute oxalate nephropathy in rats under the
      conditions of fasting and water deprivation.

PMID- 11576895
TI  - Predicting prognosis in IgA nephropathy.

PMID- 11576896
TI  - Supportive care for patients with renal disease: time for action.

PMID- 11576897
TI  - Transforming growth factor-beta as a target for treatment in diabetic
      nephropathy.

PMID- 11576898
TI  - A new role for progesterone: an agonist for mineralocorticoid receptor activation
      and pregnancy-related hypertension.

PMID- 11576899
TI  - An uncommon disease in a patient with a solitary kidney.

PMID- 11576900
TI  - Discontinuing immunosuppression in a child with a renal transplant: are there
      limits to withdrawing life support?

PMID- 11576901
TI  - Use of vascular access blood flow to evaluate vascular access.

PMID- 11576904
TI  - Rhabdomyolysis: an unusual feature with mushroom poisoning.
AB  - Rhabdomyolysis resulting from mushroom poisoning previously has been unreported
      in the literature. We present an outbreak of Russula subnigricans poisoning with
      rhabdomyolysis. The most severely ill patient presented with rhabdomyolysis,
      severe electrolyte disturbance (hyperkalemia, hypocalcemia), respiratory failure,
      acute renal failure, pulmonary edema, ventricular tachycardia, and circulatory
      shock. Mycotoxin may be the cause of rhabdomyolysis. In areas where mushroom
      gathering is common, mushroom poisoning should be included in the differential
      diagnosis of rhabdomyolysis.

PMID- 11576905
TI  - Shunt nephritis from Propionibacterium acnes in a solitary kidney.
AB  - Since its initial description in 1965, immune complex glomerulonephritis
      associated with ventriculoatrial shunts (VAS) has been reported widely in the
      literature. The most common incriminating organism is Staphylococcus epidermidis,
      but less often, an organism generally regarded as nonpathogenic, such as
      Propionibacterium acnes, has been noted as the cause. Shunt infection usually
      occurs within a few months after placement or manipulation of the shunt, and
      shunt nephritis (SN) develops gradually over months to years after. Treatment
      involves mandatory removal of the shunt and antibiotics; prognosis is variable.
      We report a case of SN with P acnes that is unusual because of its occurrence in
      a solitary kidney 6 years after shunt placement, persistently negative blood
      cultures, and normal complement levels. Percutaneous biopsy of a solitary kidney
      should be considered if it is expected that the result may guide therapy of
      progressive renal failure.

PMID- 11576906
TI  - A successfully treated case of disseminated tuberculosis-associated
      hemophagocytic syndrome and multiple organ dysfunction syndrome.
AB  - We report the case of a patient who presented with disseminated tuberculosis
      associated hemophagocytic syndrome (HPS). A 40-year-old man was admitted because
      of fatigue, fever, and renal dysfunction. Chest radiograph and computed
      tomography scan showed diffuse reticulonodular shadow, and Mycobacterium
      tuberculosis was identified. Peripheral blood counts decreased rapidly, and bone
      marrow aspiration revealed hemophagocytosis by macrophages. Despite
      antituberculous and steroid pulse therapy, multiple organ dysfunction syndrome
      developed. After plasma exchange and continuous hemodiafiltration were started,
      hypercytokinemia and vital signs improved dramatically. Although disseminated
      tuberculosis-associated HPS carries a poor prognosis, acute blood purification
      may be an effective means of treating HPS involving multiple organ dysfunction
      syndrome.

PMID- 11576907
TI  - Linezolid for treatment of vancomycin-resistant enterococcal peritonitis.
AB  - A 42-year-old woman on continuous ambulatory peritoneal dialysis (CAPD) developed
      peritonitis secondary to vancomycin-resistant Enterococcus faecium and Candida
      albicans while hospitalized for pneumonia. She was treated successfully with
      intravenous linezolid, fluconazole given by nasogastric tube, and removal of the
      peritoneal catheter. A concentration of linezolid above the minimum inhibitory
      concentration for most gram-positive pathogens, including vancomycin-resistant E
      faecium, was achieved in the dialysate fluid after an oral loading dose of 1200
      mg. Additional data are needed to establish the role of linezolid in treating
      CAPD-associated peritonitis.

PMID- 11576908
TI  - Acute renal failure secondary to spontaneous acute tumor lysis syndrome in
      myelofibrosis.
AB  - A 70-year-old man with myelofibrosis developed nonoliguric acute renal failure in
      association with acute uric acid nephropathy in the absence of chemotherapy or
      radiotherapy. The patient had an 18-month history of transfusion-dependent
      myelofibrosis and moderate chronic renal insufficiency. Admission laboratory
      findings were remarkable for severe hyperuricemia, hyperphosphatemia,
      hyperkalemia, and hypocalcemia with acute deterioration of renal function,
      consistent with a diagnosis of acute uric acid nephropathy. Treatment, including
      hemodialysis and allopurinol administration, resulted in clinical improvement
      with normalization of serum uric acid concentrations and resolution of acute
      renal failure. With long-term allopurinol therapy, renal function has remained at
      his previous baseline, and there has been no transformation to acute leukemia.
      This case represents a rare instance of acute renal failure related to the
      occurrence of acute uric acid nephropathy associated with myelofibrosis and
      emphasizes the importance of early recognition and aggressive management, which
      can lead to recovery of renal function.

PMID- 11576909
TI  - Two cases of non-O157:H7 Escherichia coli hemolytic uremic syndrome caused by
      urinary tract infection.
AB  - Escherichia coli serotype O157:H7 is a leading cause of diarrhea and hemolytic
      uremic syndrome (HUS). Because of the limitations of current diagnostic
      techniques, the prevalence of non-O157:H7 Shiga toxin-producing E coli strains is
      not known. We describe two patients with HUS in whom no E coli O157:H7 was
      demonstrable in stool cultures. On culture of the urine, the first patient was
      found to have E coli O113:H21 strain, and the second patient had E coli O6:H1
      serotype. Shiga toxin production (stx2) by the O113:H21 isolate was confirmed.
      The first patient required 15 days of peritoneal dialysis and subsequently
      recovered renal function. At last follow-up, serum creatinine was 0.9 mg/dL. The
      second patient had preservation of renal function throughout the acute illness
      with serum creatinine of 0.5 mg/dL. The clinical presentation, bacteriology,
      course, and outcome as well as epidemiologic implications of the increasing
      number of patients with E coli urinary tract infections associated with HUS are
      discussed. These cases illustrate the need to investigate patients with
      nondiarrheal HUS for infection with Shiga toxin-producing E coli of the non-O157
      strain variety.

PMID- 11576911
TI  - Proceedings of the Second International Congress on Uremia Research. April 26-28,
      2001. Nara, Japan.

PMID- 11576910
TI  - Indinavir nephropathy revisited: a pattern of insidious renal failure with
      identifiable risk factors.
AB  - Indinavir is a well-known cause of crystal-induced acute renal failure, dysuria
      and flank pain, and nephrolithiasis. Recently a more insidious tubulointerstitial
      lesion has been recognized as secondary to the drug. We report a case of a
      hepatitis C-positive patient on long-term indinavir therapy for human
      immunodeficiency virus (HIV) who developed a slowly progressive rise in serum
      creatinine. Renal biopsy revealed a diffuse interstitial infiltrate with numerous
      eosinophils and scarring. The tubules showed focal necrosis and dilation with
      elongated crystals present within their lumina. The elevated serum creatinine
      decreased to a new baseline over several months with the discontinuation of
      indinavir. We review the literature of renal syndromes associated with indinavir
      focusing on chronic progressive tubulointerstitial injury and speculate on risk
      factors and potential mechanisms of indinavir-induced renal injury.

PMID- 11576913
TI  - Paradox of risk factors for cardiovascular mortality in uremia: is a higher
      cholesterol level better for atherosclerosis in uremia?
AB  - Patients with chronic uremia have a substantially elevated risk of death from
      cardiovascular disease than do the general population. Although uremic and
      nonuremic groups share some of the risk factors for cardiovascular mortality,
      such as older age, diabetes, and inflammation, other factors appear to affect
      cardiovascular mortality in the opposite direction. For example, being overweight
      and having hyperlipidemia are established risk factors in the general population,
      whereas lower body mass index and lower plasma cholesterol have been shown to be
      risk factors for cardiovascular mortality in end-stage renal disease (ESRD). This
      paradoxical phenomenon is explained by two facts: (1) that malnutrition is a
      strong predictor of cardiovascular mortality in ESRD and (2) that plasma lipid
      levels are lowered in malnutrition. However, it is not known whether
      atherosclerosis is promoted by malnutrition or by low cholesterol level. Because
      the cardiovascular mortality rate is theoretically the product of event rate and
      fatality rate after an event, risk factors for cardiovascular mortality could
      fall into two categories: those raising the event rate and those affecting the
      fatality rate. Some factors could work both ways. Patients with ESRD show a
      significant increase in both event rate and fatality rate. Dyslipidemia is an
      independent factor affecting atherosclerotic arterial wall changes and
      cardiovascular events in ESRD. Other factors affecting the cardiovascular event
      rate in ESRD include diabetes and an elevated homocysteine level. In contrast,
      factors associated with poor survival after an event include diabetes and anemia.
      Malnutrition could be a factor causing the fatality rate to rise, although there
      is no direct evidence supporting this possibility. Further studies are needed to
      show the differential effects of a risk factor on event rate and fatality rate.
      Patients with ESRD would have a better chance of living longer by better
      management of the two categories of risk factors.

PMID- 11576914
TI  - Proteinuria and cardiovascular disease.
AB  - In the last few decades, clinical and experimental data have established
      microalbuminuria/proteinuria as an independent risk factor for renal disease and
      for progression of renal disease in patients with diabetes and in those with
      essential hypertension. Reduction of proteinuria with the use of angiotensin
      converting enzyme inhibitors has been shown in clinical trials to delay or
      stabilize the rate of progression of renal disease. This effect appears to be
      independent of any effect on blood pressure control. In conjunction with other
      therapeutic interventions such as dietary modification and control of serum
      lipids, it appears that for at least a subgroup of patients, it is possible to
      delay or prevent progression of kidney failure. More recently, evidence has
      accumulated that establishes microalbuminuria/proteinuria as an independent risk
      factor for cardiovascular morbidity and mortality even in those without other
      clinical evidence of kidney disease. There is frequently a clustering of risk
      factors in these individuals that includes insulin resistance, salt-sensitivity,
      hypertension, and dyslipidemia. The mechanism of this relationship of proteinuria
      and cardiovascular disease is unclear, but the presence of proteinuria as a
      marker for cardiovascular disease has important implications for the
      identification and treatment of individuals at risk.

PMID- 11576915
TI  - Abnormalities in uremic lipoprotein metabolism and its impact on cardiovascular
      disease.
AB  - Patients with end-stage renal disease (ESRD) suffer from a secondary form of
      complex dyslipidemia consisting of both quantitative and qualitative
      abnormalities in serum lipoproteins resulting from alterations in lipoprotein
      metabolism and composition. The prominant features of uremic dyslipidemia are an
      increase in serum triglyceride levels (due to elevated very low density
      lipoprotein [VLDL]-remnants and intermediate-density lipoprotein [IDL]) and low
      high-density lipoprotein (HDL) cholesterol. Low-density lipoprotein (LDL)
      cholesterol often is normal, but the cholesterol may originate from the
      atherogenic small and dense LDL subclass (sdLDL). The apolipoprotein B (apoB)
      containing part of the lipoprotein may undergo modifications (enzymatic- and
      advanced glycation end-product [AGE]-peptide modification, oxidation, or
      glycosilation). Modifications contribute to impaired LDL receptor-mediated
      clearance from plasma and promote prolonged circulation. While LDL particles
      undergo a vicious cycle of accumulation and modification, reverse cholesterol
      transport is also impaired due to low lecithin:cholesterol acyltransferase (LCAT)
      and paraoxonase activity. Therefore, discoid HDL particles are structurally
      altered and hepatic cholesterol clearance is limited. The composition of HDL may
      also be altered during states of inflammation. The contribution of this complex
      and atherogenic form of dyslipidemia to cardiovascular disease in patients with
      renal disease is unclear at present. Most studies are negative in demonstrating
      the predictive power of serum lipids for the development of cardiovascular
      disease. This is most likely due to interference with deteriorating aspects of
      the activated acute-phase response. Nevertheless, patients with renal disease
      belong to a very high cardiovascular risk group and dyslipidemia should most
      likely be subjected to sufficient lipid-lowering therapy in most patients.
      Because it is also still unclear whether we have available therapies with
      sufficient impact on LDL size, remnant lipoprotein-lowering, and restoration of
      HDL function, we urgently need the results from large scale intervention trials
      such as the 4D-trial and the CHORUS study.

PMID- 11576916
TI  - Effect of erythropoietin on cardiovascular diseases.
AB  - Cardiac diseases account for almost 50% of deaths in long-term dialysis patients.
      Left ventricular dysfunction is present in approximately 80% of these patients
      and is highly predictive of future ischemic heart disease, cardiac failure, and
      death. Anemia has been identified as one of several risk factors responsible for
      cardiac complications. Cardiovascular consequences of renal anemia begin
      relatively early in the course of renal failure and progress with the decline of
      renal function and also during dialysis therapy. In chronic renal failure
      patients with severe anemia (hemoglobin levels <10 g/dL), increased cardiac
      output, high left ventricular mass, left ventricular end-diastolic and end
      systolic diameters, and cardiac symptoms improve after partial correction of
      anemia (hemoglobin levels >11 g/dL according to the European Best Practice
      Guidelines). It is disappointing that normalization of hemoglobin levels has only
      minor effects with respect to regression of left ventricular hypertrophy and left
      ventricular dilation. There is no benefit of hemoglobin normalization on all
      cause mortality of dialysis patients or on survival of end-stage renal disease
      patients with congestive heart failure or ischemic heart disease. Therefore,
      prevention of renal anemia may be more efficient than its treatment. Hypertension
      is one of the major side effects of recombinant human erythropoietin (rHuEPO)
      therapy. Multiple factors are involved in rHuEPO-induced hypertension. High blood
      pressure can usually be controlled readily in the majority of the patients.

PMID- 11576917
TI  - Cardiovascular disease in end-stage renal disease patients.
AB  - This study evaluates risk factor monitoring in end-stage renal disease (ESRD)
      patients with cardiovascular disease. Death rates from cardiovascular disease in
      ESRD patients are 20 to 40 times higher than in the general population, and 72%
      of ESRD patients with an acute myocardial infarction (AMI) are dead within 2
      years of follow-up. Patients who have sustained an AMI rarely receive definitive
      testing to assess coronary circulation, and cardiac catheterization rates and
      revascularization rates are low, even after the high-risk event of an AMI. Risk
      factor intervention to treat lipid disorders in the ESRD population has received
      little attention, with the USRDS reporting that in 1998, 58% of dialysis and 64%
      of transplant patients had no lipid monitoring performed within a year. Of those
      tested, only 33% of dialysis and 27% of transplant patients had two or more tests
      within 1 year. Glycemic control monitoring in the form of HbA1c, recommended for
      diabetes management, is also underutilized in ESRD patients, with fewer than half
      receiving a single test within 1 year and only 10% receiving three or more tests.
      This raises concerns that diabetic glycemic control monitoring may be suboptimal
      in the ESRD population. The use of diabetic eye examinations and diabetic glucose
      monitoring is also low, as are influenza vaccination rates. These data suggest
      that the clinical care of cardiovascular disease in the ESRD patients needs more
      attention.

PMID- 11576918
TI  - Atherogenic lipoproteins in end-stage renal disease.
AB  - Cardiovascular mortality is substantially higher in patients with end-stage renal
      disease (ESRD). Lipoprotein abnormality in ESRD is one of the possible risk
      factors for advanced atherosclerosis. Uremic dyslipidemia is characterized by
      increased plasma triglycerides due to elevated very low density lipoprotein
      (VLDL) and decreased high-density lipoprotein (HDL). Plasma total or low-density
      lipoprotein (LDL) cholesterol is rarely elevated in hemodialysis patients. The
      "LDL" by standard assay methods consists of intermediate-density lipoprotein
      (IDL) and LDL devoid of IDL. Although "LDL" is not increased, IDL is markedly
      elevated in uremic plasma. We previously showed that aortic stiffness of
      hemodialysis patients was associated positively with VLDL, IDL, and LDL devoid of
      IDL and that IDL is the best lipoprotein predictor of aortic stiffness. The IDL
      level is correlated positively with plasma total cholesterol, triglyceride, and
      "LDL" levels. Importantly, increased IDL is found in ESRD patients with "normal"
      "LDL"cholesterol levels, indicating that the target "LDL" level should be lower
      than that for the general population. More than 40% of hemodialysis patients
      exceeded the upper limit (15 mg/dL, 95th percentile level) of IDL cholesterol in
      healthy subjects. Based on a linear relationship between IDL and "LDL," the
      normal range of IDL cholesterol (<15 mg/dL) corresponds to "LDL" cholesterol by
      the Friedewald equation below 100 mg/dL in hemodialysis patients. Statins
      effectively and safely reduce "LDL," including IDL in patients treated with
      hemodialysis or peritoneal dialysis. The effect of lipid-lowering therapy on
      cardiovascular mortality in ESRD, however, awaits the results of ongoing
      prospective trials.

PMID- 11576919
TI  - Vascular calcification and inorganic phosphate.
AB  - Vascular calcification is highly correlated with elevated serum phosphate levels
      in uremic patients. To shed light on this process, we examined the ability of
      extracellular inorganic phosphate (Pi) levels to regulate human aortic smooth
      muscle cell (HSMC) culture mineralization in vitro. When cultured in media
      containing normal physiological levels of Pi (1.4 mmol/L Pi), HSMC grew in
      monolayers and did not mineralize. In contrast, HSMC cultured in media containing
      Pi levels comparable to those seen in hyperphosphatemic individuals (>1.4
      mmol/L), showed dose-dependent increases in cell culture calcium deposition.
      Mechanistic studies showed that elevated Pi treatment of HSMC also enhanced the
      expression of the osteogenic markers, osteocalcin and Cbfa-1. The effects of
      elevated Pi on HSMC were mediated by a sodium-dependent phosphate cotransporter
      (NPC), as indicated by the ability of the specific NPC inhibitor, phosphonoformic
      acid (PFA), to dose-dependently inhibit Pi-induced calcium deposition as well as
      osteocalcin and Cbfa-1 gene expression. Using polymerase chain reaction and
      Northern blot analyses, the NPC in HSMC was identified as Pit-1 (Glvr-1), a
      member of the type III NPCs. Interestingly, platelet-derived growth factor-BB
      (PDGF-BB), a potent atherogenic stimulus, increased the maximum velocity (Vmax)
      but not the affinity (Km) of phosphate uptake, enhanced the expression of Pit-1
      mRNA, and induced HSMC culture calcification in a time- and dose-dependent
      manner. Importantly, in the presence of PDGF, HSMC culture calcification occurred
      under normophosphatemic conditions. These data suggest that elevated Pi may
      directly stimulate HSMC to undergo phenotypic changes that predispose to
      calcification and may help explain both the phenomena of human metastatic
      calcification under hyperphosphatemic conditions as well as increased
      calcification in PDGF-rich atherosclerotic lesions.

PMID- 11576921
TI  - Monckeberg's medial sclerosis and inorganic phosphate in uremia.
AB  - Monckeberg's medial sclerosis (MMS) is one of the characteristic calcified
      lesions of uremic artery disease and often exhibits osseous metaplasia. Although
      its pathogenic mechanism is largely unknown, MMS may contain two different
      pathologic processes: degenerative process leading to apoptosis or necrosis of
      medial smooth muscle cells and osteogenic process leading to formation of bone
      like structures. It has long been known that calcification follows necrosis.
      Apoptotic/necrotic cells often release matrix vesicles or membranous cellular
      degradation products resulting from disintegration of the cells that frequently
      serve as the nidus of calcification. On the other hand, vascular cells may
      exhibit osteoblastic phenotype in vitro, and some of the markers for osteoblastic
      differentiation and noncollagenous proteins regulating mineralization have been
      demonstrated in calcified arterial lesions. As a possible etiologic factor
      inducing these two responses, hyperphosphatemia among various metabolic
      disturbances recognized in uremia may play an important role in the development
      of MMS in uremia.

PMID- 11576920
TI  - The heart in uremia: role of hypertension, hypotension, and sleep apnea.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in end
      stage renal disease. Causes include those usually found in the general
      population, those related to the uremic status, and those related to dialytic
      treatment. Hypertension, hypotension, anemia, hypoalbuminemia, malnutrition,
      dyslipidemia, reactive C protein, calcium-phosphate product, dialysis modalities,
      and hyperhomocysteinemia are discussed extensively. Special emphasis is put on
      hyperparathyroidism as a traditional toxin. The emergent role of sleep apnea has
      been confirmed in animal models as well as in humans studied using
      polysomnography. There are difficulties in diagnosing coronary disease, because
      angiography is not risk-free, is expensive, and should be reserved for patients
      having symptoms of heart failure and/or patients having diabetes mellitus, and/or
      patients entering a transplantation list. This allows patients with coronary
      disease to undergo coronary artery bypass (preferably) or percutaneous
      transluminal angioplasty. Patients for whom surgery is not appropriate should be
      treated using more traditional medical procedures.

PMID- 11576922
TI  - Efficient and ligand-dependent regulated erythropoietin production by naked dna
      injection and in vivo electroporation.
AB  - The development of an in vivo gene transfer approach to deliver physiologic
      levels of recombinant proteins to the systemic circulation would represent a
      significant advance in the treatment of protein deficiencies-disorders. However,
      the ability to regulate transgene expression will become paramount for safety and
      efficacy in gene transfer therapy. We have described the construction of an
      efficient and ligand-dependently regulated erythropoietin (EPO) production system
      using naked plasmid and in vivo electroporation. Two plasmids, one encoding the
      chimeric GeneSwitch protein and the other encoding an inducible transgene for
      human EPO, were developed. Modulation of the level of secretion of EPO into the
      serum was achieved by intraperitoneal administration of mifepristone (MFP). Rats
      were divided into 4 groups: one group received EPO plasmid with MFP for 30 days,
      a second group received with EPO plasmid MFP for 9 days, a third group received
      EPO plasmid without MFP, and a fourth group received control plasmid. A pair of
      electrodes was inserted into the muscle of the right thigh and 100 micrograms of
      each plasmid was injected. In vivo electrporation (8 times at 100 V for 50
      milliseconds) was performed. The presence of vector-derived EPO mRNA was detected
      by reverse transcriptase-polymerase chain reaction only in the EPO and MFP(+)
      group. The hematocrit levels increased continuously from the preinjection level
      of 42.7% to 53.8% on day 28 in the EPO and MFP(+) group. The serum EPO levels
      increased only in the EPO and MFP(+) group. There was no significant change in
      hematocrit levels and EPO levels in the EPO and MFP(-) group. These results
      demonstrate that EPO gene transfer with the GeneSwitch system by in vivo
      electroporation is a useful procedure for efficient and drug-dependent regulated
      delivery of EPO.

PMID- 11576923
TI  - Increased Fas antigen in uremia accelerates adhesion of mononuclear cells to
      endothelial and sinovial cells via stimulated hyaluronan production.
AB  - We examined influences of increased soluble Fas (sFas) and hyaluronan in uremia
      on apoptosis and peripheral blood mononuclear cell (MNC) adhesiveness.
      Synovocytes, human umbilical cord endothelial cells (HUVEC), human coronary
      artery smooth muscle cells (CASMC), and MNC were prepared in this study. In
      cultures of synovocytes, HUVEC, and CASMC, sFas or high molecular hyaluronan was
      added to media at medium change. After 1 day, Fas-positive cells were calculated
      by fluorescence-activated cell sorting. Uremic level of sFas enhanced Fas
      positive cells in all cell lines (P < 0.01) not in CASMC. On the contrary,
      hyaluronan inhibited Fas expression in all cell lines (P < 0.05). In culture with
      uremic serum, Fas were induced in all cell lines. At this time, the hyaluronan
      levels of the supernatant were measured and hyaluronan production was estimated.
      In contrast to the results using sFas supplement, hyaluronan production was
      increased in culture with sFas and uremic sera. MNC adhesiveness was increased in
      synovocytes and HUVEC lines by adding hyaluronan or sFas. Higher adherent cell
      numbers were recognized when both sFas and hyaluronan were added to the media. A
      most remarkable increase in cell numbers was observed in uremic MNC suspension as
      compared with that of MNC from healthy subjects. In conclusion, these results
      indicate that increased sFas in uremia stimulates apoptosis and hyaluronan
      production. Both sFas and hyaluronan are responsible for accelerated MNC
      adhesiveness in uremia.

PMID- 11576924
TI  - Insulin secretion in uremia.

PMID- 11576925
TI  - Carnitine metabolism in uremia.
AB  - Carnitine is a conditionally essential metabolite that plays a critical role in
      cell physiology by participating in transesterification reactions and preventing
      organic acid accumulation. A number of disease states are characterized by
      carnitine depletion that may lead to metabolic and clinical disturbances. In
      maintenance hemodialysis, carnitine is lost through dialytic membranes, leading
      in selected patients to carnitine depletion with a relative increase of the
      esterified forms. Carnitine supplementation after or during dialysis counteracts
      such alterations and may be associated with some clinical benefits. Recent meta
      analyses of the literature indicate that carnitine supplementation in
      hemodialysis patients may improve the hematological status (allowing a reduction
      of the requirement for erythropoietin), the exercise tolerance, the plasma lipid
      profile, and the intradialytic symptoms. In addition, carnitine supplementation
      may improve cardiac functions, protein metabolism, and insulin resistance.
      Carnitine supplementation has been recently approved by the US Food and Drug
      Administration not only for the treatment, but also for the prevention of
      carnitine depletion in dialysis patients. Furthermore, clinical guidelines
      developed by both American and European nephrological societies suggest that a
      trial with carnitine supplementation could be recommended in selected dialysis
      patients who do not adequately respond to standard therapy for certain
      conditions, such as severe and persistent muscle cramps or hypotension during
      dialysis, lack of energy affecting quality of life, skeletal muscle weakness or
      myopathy, cardiomyopathy, and anemia of uremia unresponsive to or requiring large
      doses of erythropoietin.

PMID- 11576926
TI  - The National Kidney Foundation K/DOQI clinical practice guidelines for dietary
      protein intake for chronic dialysis patients.
AB  - This paper discusses two of the National Kidney Foundation Kidney Disease
      Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for nutrition
      in chronic renal failure. These are the guidelines that recommend a dietary
      protein intake of 1.2 g protein/kg body weight/day for clinically stable
      maintenance hemodialysis (MHD) patients (Guideline 15) and 1.2 to 1.3 g
      protein/kg/day for clinically stable chronic peritoneal dialysis (CPD) patients
      (Guideline 16). These recommended protein intakes are greater than the usually
      ingested protein intakes of MHD and CPD patients and are also greater than the
      recommended protein intakes for healthy, nonpregnant, nonlactating adults. The
      possible mechanisms that engender these increased protein needs include (1) the
      substantial quantity of amino acids, peptides, and proteins removed by the
      dialysis procedure and (2) the protein catabolic or antianabolic state caused by
      the uremic milieu, the inflammatory state, the oxidative and carbonyl stress, and
      the bioincompatible dialysis materials to which MHD and CPD patients are exposed.
      There are a number of nitrogen balance studies that have been performed to
      identify the dietary protein needs of MHD and CPD patents. The results of this
      research as well as some of the methodological limitations of these studies are
      reviewed. The concepts of the average dietary protein intake required to maintain
      protein balance in MHD or CPD patients and the safe protein intake that will
      maintain protein balance in virtually all MHD and CPD patients are discussed.

PMID- 11576927
TI  - Effect of chronic renal failure on nitric oxide metabolism.
AB  - Chronic renal failure (CRF) is associated with hypertension, endothelial
      dysfunction, and a strong propensity for arteriosclerotic cardiovascular disease.
      Nitric oxide (NO) is an endogenous modulator with diverse biological functions.
      Chronic inhibition of NO synthases (NOS) has been shown to cause hypertension and
      vasculopathy. In light of these considerations, numerous studies have explored
      the effect of CRF on NO metabolism with the assumption that NO deficiency may be
      involved in the pathogenesis of cardiovascular and other consequences of uremia.
      The purpose of this review is to provide a brief overview of the effect of CRF on
      (1) the bioavailability of NO substrate, L-arginine; (2) the expression of NOS
      isoforms in the relevant organs; (3) the interaction of NO with reactive oxygen
      species that are known to be increased in CRF, and (4) the accumulation of uremic
      inhibitors of NOS.

PMID- 11576928
TI  - Thyroid function in patients with chronic renal failure.
AB  - Chronic renal failure affects thyroid function in multiple ways, including low
      circulating thyroid hormone concentration, altered peripheral hormone metabolism,
      disturbed binding to carrier proteins, possible reduction in tissue thyroid
      hormone content, and increased iodine store in thyroid glands. Both plasma
      triiodothyronine (T(3)) and thyroxine (T(4)) are reduced. The low serum T(3) is
      not due to increased T(3) degradation or to decreased thyroidal T(3) secretion
      but is a result of impaired extrathyroidal T(4) to T(3) conversion. The reduction
      in T(4) is attributed to the presence of circulating inhibitors, which impair
      binding of T(4) to thyroxine-binding globulin. Despite decreased circulating T(4)
      and T(3), thyroid-stimulating hormone (TSH) is not elevated. This absence of TSH
      elevation is not due to dysfunction of the hypothalamo-pituitary axis, because
      truly hypothyroid renal failure patients can mount a high TSH response. Thyroid
      hormone losses during hemodialysis and peritoneal dialysis are trivial and do not
      require replacement. Serum inorganic iodide and thyroidal iodine content are
      increased in renal failure patients, and thyroid gland enlargement is frequently
      encountered. Experiments performed to correct the low serum T(3) level by
      administration of small doses of LT(3) to renal failure patients resulted in
      lesser nitrogen balance, greater leucine flux, and protein degradation. We
      speculate that the low thyroid state in uremia serves to defend against protein
      wasting and that misguided attempts to replete thyroid hormone stores may worsen
      protein malnutrition.

PMID- 11576929
TI  - Metabolic consequences of hyperhomocysteinemia in uremia.
AB  - An elevated blood level of homocysteine (Hcy), a sulfur amino acid, is associated
      with increased cardiovascular risk. Hcy is generated from S-adenosylhomocysteine
      (AdoHcy), the demethylated product of S-adenosylmethionine (AdoMet) in
      transmethylation reactions. AdoHcy is a competitive inhibitor of AdoMet-dependent
      methyltransferases. AdoHcy accumulation is prevented by rapid metabolism of its
      products. Chronic renal failure (CRF) is almost constantly associated with
      hyperhomocysteinemia. It has been shown that: (1) AdoHcy concentration is
      significantly increased and the AdoMet-AdoHcy ratio is reduced in erythrocytes of
      patients with CRF; (2) erythrocyte membrane protein methyl esterification,
      catalyzed by the enzyme protein L-isoaspartyl O-methyltransferase (PCMT; EC
      2.1.1.77), is reduced in CRF; PCMT catalyzes a repair reaction involved in the
      conversion of an isopeptide bond (detrimental to protein structure and function)
      into a normal peptide bond; (3) D-aspartate residues, a side product of protein
      methylation and repair, are significantly reduced in erythrocyte membrane
      proteins of patients with CRF; and (4) folate treatment significantly reduces
      plasma Hcy levels and improves AdoMet-AdoHcy ratios. Stable isotope studies
      recently confirmed that the rate of methyl transfer reactions is significantly
      reduced in uremia. Additional evidence, obtained by independent groups, is
      consistent with this interpretation. We recently found increased isoaspartyl
      content of circulating plasma protein levels, particularly albumin, which was
      only partially reduced after folate treatment, in uremia. This kind of molecular
      damage possibly is caused by protein increased intrinsic instability as a result
      of interference with the uremic milieu. In conclusion, Hcy is an uremic toxin
      involved in protein molecular damage through the inhibition of methylation
      reactions and protein PCMT-mediated repair.

PMID- 11576930
TI  - Treatment of hyperhomocysteinemia in end-stage renal disease.
AB  - Mild to moderate hyperhomocysteinemia (Hhcy) is observed in more than 90% of
      patients with end-stage renal disease (ESRD) undergoing maintenance dialysis and
      approximately 60% to 70% of chronic stable renal transplant recipients. The
      reported association between Hhcy and the development of arteriosclerotic
      cardiovascular disease may account, in part, for the disproportionate risk for
      cardiovascular morbidity and mortality in patients with chronic renal disease.
      Treatment with the recommended daily allowances of folic acid and vitamins B(6)
      and B(12), which consistently normalizes total homocysteine (tHcy) levels in the
      general population free of chronic renal disease, rarely results in the
      normalization of tHcy levels in patients with ESRD. A large number of
      investigations now have shown that even grossly supraphysiological doses of folic
      acid and vitamins B(6) and B(12) fail to normalize tHcy levels in more than 90%
      of dialysis-dependent patients with ESRD with baseline Hhcy. Conversely, such
      treatment consistently normalizes tHcy levels among hyperhomocysteinemic chronic
      stable renal transplant recipients or patients with mild to moderate renal
      insufficiency. A randomized, placebo-controlled, tHcy-lowering intervention trial
      involving approximately 4,000 chronic stable US renal transplant recipients (RO1
      DK56486 01A2) will soon be underway to formally address the tenable hypothesis
      that tHcy-lowering treatment may reduce the risk for arteriosclerotic outcomes.
      Data from this trial should be applicable to patients with chronic renal
      insufficiency in general.

PMID- 11576931
TI  - Association of endothelial dysfunction with sulfur amino acid metabolism in
      chronic renal failure.
AB  - Moderate hyperhomocysteinemia and endothelial dysfunction are consistent findings
      in uremic patients. Although an exceedingly high incidence of cardiovascular
      disease and stroke has been shown in dialysis patients, several traditional risk
      factors are relatively limited predictors. Hyperhomocysteinemia could be a
      principal candidate for endothelial dysfunction. Recent findings suggest that
      hyperhomocysteinemia may impair endothelial function by the generation of oxygen
      species and decreased nitric oxide (NO) bioavailability. However, the precise
      mechanisms underlying the link between hyperhomocysteinemia and impaired
      endothelial function in chronic renal failure remain unclear. Endothelial
      function was evaluated by the response to reactive hyperemia and donor of NO. We
      observed impairment in both endothelium-dependent and endothelium-independent
      vasodilation in dialysis patients. These data suggest that patients with chronic
      renal failure may have defective NO-mediated function in the endothelium and
      smooth muscle of vessels. Most reports have shown only impairment of endothelium
      dependent vasodilation, whereas another report observed impaired smooth muscle
      function and intact endothelial function. Only a few previous observations
      included a full set of vascular function data, such as baseline vessel diameter,
      reactive hyperemia, and responses of endothelium to hyperemia and NO donor,
      although all these observations could be essential for comparison with other
      reports. Treatment with folic acid was reported to reduce plasma homocysteine
      levels, but not to normal levels, and failed to improve impaired endothelial
      function in patients in a predialysis phase and on maintenance dialysis therapy.
      Another investigation, directed at reducing homocysteine levels in earlier stages
      of renal failure, may be necessary to clarify the link between
      hyperhomocysteinemia and endothelial function.

PMID- 11576932
TI  - Advanced glycation end products and the progressive course of renal disease.
AB  - In experimental and human diabetic nephropathy (DN), it has been shown that
      advanced glycation end products (AGEs), in particular, carboxymethyl-lysine and
      pentosidine, accumulate with malondialdehyde in glomerular lesions in relation to
      disease severity and in the presence of an upregulated receptor for AGE (RAGE) in
      podocytes. Toxic effects of AGEs result from structural and functional
      alterations in plasma and extracellular matrix (ECM) proteins, in particular,
      from cross-linking of proteins and interaction of AGEs with their receptors
      and/or binding proteins. In mesangial and endothelial cells, the AGE-RAGE
      interaction caused enhanced formation of oxygen radicals with subsequent
      activation of nuclear factor-kappaB and release of pro-inflammatory cytokines
      (interleukin-6, tumor necrosis factor-alpha), growth factors (transforming growth
      factor-beta1 [TGF-beta1], insulin-like growth factor-1), and adhesion molecules
      (vascular cell adhesion molecule-1, intercellular adhesion molecule-1). In
      tubular cells, incubation with AGE albumin was followed by stimulation of the
      mitogen-activating protein (MAP) kinase pathway and its downstream target, the
      activating protien-1 (AP-1) complex, TGF-beta1 overexpression, enhanced protein
      kinase C activity, decreased cell proliferation, and impaired protein degradation
      rate, in part caused by decreased cathepsin activities. The pathogenic relevance
      of AGEs was further verified by in vivo experiments in euglycemic rats and mice
      by the parenteral administration of AGE albumin, leading in the glomeruli to TGF
      beta1 overproduction, enhanced gene expression of ECM proteins, and morphological
      lesions similar to those of DN. Evidence for the pathogenic relevance of AGEs in
      DN also comes from experimental studies in which the formation and/or action of
      AGEs was modulated by aminoguanidine, OPB-9195, pyridoxamine, soluble RAGEs,
      serine protease trypsin, and antioxidants, resulting in improved cell and/or
      renal function.

PMID- 11576933
TI  - Localization of imidazolone in the peritoneum of capd patients: a factor for a
      loss of ultrafiltration.
AB  - The presence of dicarbonyl compounds, potent precursors of advanced glycation end
      products (AGEs), has been recognized in unused peritoneal dialysis (PD) fluids.
      Accumulation of AGEs has been implicated in the alteration of peritoneal membrane
      properties during continuous ambulatory peritoneal dialysis (CAPD) therapy. To
      determine whether imidazolone, an AGE specifically derived from 3-deoxyglucosone
      (3-DG), contributes to a decrease in ultrafiltration (UF) capacity of the
      peritoneal membrane in CAPD patients, we immunohistochemically evaluated the
      localization of imidazolone in peritoneal tissues from CAPD patients. Mesothelial
      thickening in the peritoneum was found in six of seven CAPD patients. Imidazolone
      distinctly accumulated in peritoneal tissues of CAPD patients, whereas it was
      hardly detected in those of patients with nonrenal disease. CAPD patients with a
      low UF capacity showed more extensive peritoneal deposition of imidazolone and
      more pronounced mesothelial thickening than those with a normal UF capacity. A
      CAPD patient with sclerosing peritonitis showed the most abundant localization of
      imidazolone among all CAPD patients. Gas chromatography/mass spectrometry showed
      that unused PD fluids contained high 3-DG concentrations (mean, 34.6 +/- 14.1
      [SD] microgram/mL). In conclusion, the accumulation of imidazolone was noted in
      peritoneal tissues of CAPD patients, which preceded a decrease in UF capacity.
      Imidazolone modification may alter the quality of peritoneal membranes,
      presumably leading to a loss of UF and finally the development of sclerosing
      peritonitis.

PMID- 11576934
TI  - Platelet aggregation and prostaglandin metabolism in uremic patients.
AB  - The pathogenesis of depressed platelet activity in uremia is still unknown. The
      influence of some uremic toxins on platelet aggregation (PLA) and prostaglandin
      metabolism in 50 uremic patients treated by hemodialysis (HD) or continuous
      ambulatory peritoneal dialysis (CAPD) was studied. Fifty-seven healthy volunteers
      (HVs) served for reference values. Adenosine diphosphate (ADP) and thrombin (Thr)
      were used as agonists of PLA. PLA was determined using the Born method.
      Malonyldialdehyde (MDA) levels in platelets as an indicator of prostaglandin
      metabolism, after stimulation with arachidonic acid, were measured according to
      Stuart. The relationship of PLA and prostaglandin metabolism with plasma
      concentrations of methylguanidine (MG), guanidinosuccinic acid (GSA), and
      creatinine (Cr) was assessed. PLA-ADP values in regular HD patients (42 +/- 5 mm)
      were significantly lower than in CAPD patients (65 +/- 8 mm) and HVs (73 +/- 3
      mm). PLA-Thr values in HD patients (25 +/- 4 mm) were significantly lower than in
      CAPD patients (34.9 mm) and HVs (36 +/- 3 mm). MDA levels in HD patients (7 +/- 1
      nmol/L/10(9)) were significantly lower than in CAPD patients (12 +/- 2
      nmol/L/10(9)) and HVs (15 +/- 1 nmol/L/10(9)). In HD patients, inverse
      correlations of PLA-ADP with MG levels (r = -0.92), PLA-Thr with Cr levels (r = 
      89), and MDA levels with GSA levels (r = -0.86) were found. In CAPD patients, no
      relationship of PLA and MDA with uremic toxins was observed. Depressed activity
      of platelets and prostaglandin metabolism was strongly expressed in HD patients.

PMID- 11576935
TI  - Erectile dysfunction in uremic dialysis patients: diagnostic evaluation in the
      sildenafil era.
AB  - The two words that mean sexual dysfunction, impotence and erectile dysfunction
      (ED), express two different concepts. Impotence is a general male sexual
      dysfunction that includes libidinal, orgasmic, and ejaculatory dysfunction. ED is
      the inability to achieve or maintain an erection sufficient to allow satisfactory
      sexual intercourse and is part of the general male sexual dysfunction termed
      impotence that includes libidinal, orgasmic, and ejaculatory dysfunction. Uremic
      men of different ages report a variety of sexual problems, including sexual
      hormonal pattern alterations, reduction in or loss of libido, infertility, and
      impotence, conditioning their well-being status. In evaluating and treating
      sexual dysfunction, a nephrologist must consider factors involved in its
      pathogenesis, such as hypothalamic-pituitary-gonadal axis alterations,
      psychological problems related to chronic disease, secondary hyperparathyroidism,
      anemia, autonomic neuropathy, derangements in arterial supply or venous outflow,
      and the normal structure of cavernous body smooth muscle cells. The introduction
      of sildenafil to treat impotent patients has completely changed the approach to
      evaluating these subjects because this drug is considered an effective well
      tolerated treatment for men with ED. In the past, we proposed an algorithm that
      gave the opportunity to explore the previously mentioned factors using such
      instrumental interventions as the nocturnal penile tumescence test, penile echo
      color Doppler, nervous conduction velocity, and cavernous body biopsy, addressed
      to prescribe needed surgical or medical interventions. The complexity of the
      proposed algorithm requires many diagnostic procedures and much time and economic
      resources to localize the pathological lesions responsible for ED. Because of the
      new oral drug sildenafil, we propose a new algorithm to test the possibility of
      obtaining an erection and classify patients as responders or nonresponders to the
      sildenafil test.

PMID- 11576936
TI  - Autonomic dysfunction in uremia.
AB  - Autonomic nervous system dysfunction is a common feature in uremia and may have a
      number of clinical sequelae. Simple cardiovascular reflex screening can be
      performed in patients during conservative treatment, on periodic dialysis
      therapy, or after kidney transplantation to diagnose and follow up autonomic
      function impairment. Other approaches, such as heart-rate variability studies in
      the frequency domain by power spectral analysis, can provide a more accurate
      investigation of the disease.

PMID- 11576937
TI  - Central nervous dysfunction in uremia.
AB  - The mechanisms of central nervous system dysfunction in uremia are multifactorial
      and only partially characterized. Studies using sealed presynaptic nerve
      terminals (synaptosomes) for in vitro ion transport and metabolism of
      neurotransmitter in chronic renal failure (CRF) neuronal cell culture and in vivo
      brain structure microdialysis generated significant new information. An increase
      in total calcium content of the cerebral cortex accompanied by increased levels
      of cytosolic calcium ([Ca(2+)]i) in synaptosomes are common findings in rats with
      CRF. Mechanisms leading to the increase in [Ca(2+)]i include increased calcium
      uptake mediated by parathyroid hormone and decreased activity of Na(+),K(+)
      adenosine triphosphatase (ATPase) and Ca(2+)-ATPase of synaptosomes in CRF rats.
      Moreover, these synaptosomes respond inappropriately to depolarization, which can
      impair neurotransmitter metabolism. Brain gamma-aminobutyric acid content,
      norepinephrine, and acetylcholine release uptake and degradation are affected by
      uremia. These may lead to certain somatic, behavioral, and motor dysfunctions in
      uremia. Many derangements of the central nervous system in uremia appear to be
      mediated by secondary hyperparathyroidism of CRF because parathyroidectomy of
      animals with CRF prevented the increase in basal levels of [Ca(2+)]i and
      derangements in neurotransmitter metabolism. The role of other neurotoxins, such
      as guanidinosuccinic acid, are also reviewed.

PMID- 11576938
TI  - Depressed cerebral oxygen metabolism in patients with chronic renal failure: a
      positron emission tomography study.
AB  - To elucidate brain oxygen metabolism in uremic patients, regional cerebral blood
      flow (rCBF), oxygen extraction (rOEF), and oxygen metabolism (rCMRO(2)) were
      measured by positron emission tomography (PET) in 10 hemodialysis (HD) patients
      and 13 predialysis patients with chronic renal failure (CRF). Data were compared
      with 20 nonuremic patients (controls) without neurological abnormalities,
      congestive heart failure, history of cerebrovascular accident, diabetes mellitus,
      or symptomatic brain lesion on magnetic resonance imaging. In the hemisphere,
      rCMRO(2) in both HD (1.82 +/- 0.10 mL/min/100 g) and CRF patients (1.95 +/- 0.09
      mL/min/100 g) showed significantly lower values compared with controls (2.23 +/-
      0.05 mL/min/100 g; P < 0.01). Hemispheric rCBF in HD (35.6 +/- 2.1 mL/100 g/min)
      and CRF patients (36.1 +/- 2.1 mL/100 g/min) was not different from controls
      (31.8 +/- 1.4 mL/100 g/min). Hemispheric rOEF in CRF patients (45.7% +/- 1.6%)
      was significantly greater than that in controls (40.5% +/- 1.2%; P < 0.02), but
      rOEF in HD patients (43.7% +/- 1.9%) did not increase significantly. These
      tendencies were similar in all regions of interest, especially cerebral cortices.
      All PET parameters in frontal cortices tended to show the lowest values in
      patients with renal failure. For all HD patients, rCBF in both the frontal cortex
      and white matter correlated inversely with HD therapy duration (P < 0.05). In
      conclusion, brain oxygen metabolism is depressed in patients with renal failure
      on or before the start of HD therapy. The cause for depressed brain oxygen
      metabolism is considered to be either dysregulation of cerebral circulation or
      lower brain cell activity.

PMID- 11576939
TI  - Role of connective tissue growth factor in profibrotic action of transforming
      growth factor-beta: a potential target for preventing renal fibrosis.
AB  - Tubulointerstitial fibrosis is a crucial process determining the progression and
      prognosis of various renal diseases. Connective tissue growth factor (CTGF), a
      novel fibrogenic protein induced by transforming growth factor-beta (TGF-beta),
      is upregulated in various clinical and experimental nephropathies, but the
      significance of CTGF in the profibrotic action of TGF-beta is still poorly
      defined. To explore the implication of CTGF in renal fibrosis, we investigated
      gene expression of CTGF, fibronectin, and alpha1(I) collagen in an obstructive
      nephropathy model in rats. Furthermore, to elucidate the role of CTGF in TGF-beta
      stimulated extracellular matrix accumulation, we analyzed the effects of blockade
      of endogenous CTGF using antisense oligodeoxynucleotides (ODNs) in cultured rat
      renal fibroblasts. After unilateral ureteral obstruction, TGF-beta1 and CTGF
      messenger RNA (mRNA) expression in the obstructed kidney was coordinately
      upregulated from the early stage of interstitial fibrosis, followed by marked
      induction of fibronectin and alpha1(I) collagen mRNA expression. In cultured
      normal rat kidney fibroblast (NRK-49F) cells, CTGF antisense ODN transfection
      significantly attenuated TGF-beta1-induced fibronectin and alpha1(I) collagen
      mRNA expression compared with control reverse ODNs. These results indicate that
      CTGF has a crucial role in the profibrotic action of TGF-beta in renal
      fibroblasts, providing a potential therapeutic target against tubulointerstitial
      fibrosis.

PMID- 11576940
TI  - Impaired secretion of parathyroid hormone is coherent to diabetic hemodialyzed
      patients.
AB  - Diabetic bone disease is characterized by low bone turnover resulting from
      impaired secretion of parathyroid hormone (PTH). However, it was suggested that
      the difference in duration of hemodialysis (HD) therapy and age of patients
      between HD patients with and without diabetes mellitus (DM) may be responsible
      for a significant reduction in serum intact PTH (iPTH) level in HD patients with
      DM. The present study showed that although such major factors affecting PTH
      secretion as age, sex, HD duration, and serum calcium, phosphate, and magnesium
      levels did not differ significantly between HD patients with and without DM,
      serum iPTH levels were still significantly lower in HD patients with than without
      DM. Among biochemical markers for bone metabolism, serum levels of intact
      osteocalcin (iOC) and deoxypyridinoline (DPD) were significantly lower in HD
      patients with than without DM, whereas serum bone-specific alkaline phosphatase,
      pyridinoline, and beta-crosslaps did not differ significantly between the two
      groups of patients. In summary, our findings indicate that PTH secretion may be
      significantly impaired in HD patients with DM compared with those without DM, and
      serum iOC and DPD are bone markers sensitive enough to detect low bone turnover
      in HD patients with DM.

PMID- 11576941
TI  - Genetic aspects of secondary hyperparathyroidism in uremia.
AB  - In addition to the well-known uremia-related factors calcium, phosphate, and
      vitamin D, genetic polymorphisms and gene mutations appear to have a role as well
      in modulating parathyroid function. Allelic polymorphisms of the vitamin D
      receptor gene have been most often examined but to date their precise place is
      not yet certain in patients with chronic renal failure. The frequent
      transformation of parathyroid cell proliferation from polyclonal to monoclonal
      growth in patients with severe secondary hyperparathyroidism must be attributed
      to mutations or deletions of various tumor-suppressor genes, and probably more
      rarely also to an activation of tumor-enhancer genes.

PMID- 11576942
TI  - Clinical effects of maxacalcitol on secondary hyperparathyroidism of uremic
      patients.
AB  - Maxacalcitol (22-oxacalcitriol [OCT]) is a newly developed vitamin D analogue in
      Japan. OCT has shown less calcemic action and a strong suppressive effect on
      parathyroid hormone (PTH) in uremic rats and dogs. In uremic patients with
      secondary hyperparathyroidism, OCT dose-dependently suppressed PTH secretion and
      increased serum calcium levels. However, more than 60% of patients achieved a
      greater than 30% decrease in intact PTH level from baseline with long-term OCT
      treatment up to 1 year without an unphysiological increase in mean serum calcium
      levels. Long-term treatment also brought about a reduction in bone metabolic
      markers, including bone alkaline phosphatase, tartrate-resistant acid
      phosphatase, and bone gra-protein. These results suggest that although careful
      attention should be paid to the onset of hypercalcemia and oversuppression of
      PTH, OCT is one of the effective tools for the treatment of secondary
      hyperparathyroidism.

PMID- 11576943
TI  - Skeletal resistance to pth as a basic abnormality underlying uremic bone
      diseases.
AB  - Skeletal resistance to parathyroid hormone (PTH) was suggested initially as a
      mechanism of PTH hypersecretion in uremia. Because of the effective suppression
      of PTH by recently developed therapeutic modalities, this background abnormality
      has been uncovered and currently recognized as relative hypoparathyroidism in
      terms of its relation to bone turnover. Thus, PTH levels two to three times
      greater than normal are usually required to keep bone turnover normal in uremia.
      Recent studies suggested that PTH activity may be overestimated using the
      conventional intact PTH assay. In addition, several steps to osteoclastogenesis
      are suspected to be disturbed in uremia. Additional studies at cellular and
      molecular levels are needed to establish preventive and therapeutic modalities
      for this abnormality.

PMID- 11576944
TI  - Osteoclastogenesis and osteoclast activation in dialysis-related amyloid
      osteopathy.
AB  - Dialysis-related amyloid osteopathy (DRAO) is characterized by local
      osteoarticular lytic lesions, which sometimes cause a pathological fracture and
      reduce the quality of life in affected patients. In DRAO, active osteoclastic
      bone resorption is found at the bone surface facing the invaded synovial tissue
      and/or intervertebral disc, whereas reactive bone formation is absent. The eroded
      bone surface is covered with osteoclasts, suggesting the local promotion of
      osteoclastogenesis and osteoclast activation around DRAO. Inflammatory cells
      infiltrating the synovial tissue are likely to promote inflammatory osteolysis.
      Three possible pathways can be considered for the osteoclastogenesis and/or
      osteoclast activation in inflammatory osteolysis in DRAO: (1) indirect action of
      the inflammatory cytokines through the receptor activator of nuclear factor
      kappaB ligand/osteoprotegerin ligand (RANKL/OPGL) expression in osteoblasts, (2)
      direct action of inflammatory cytokines, and (3) RANKL/OPGL expression in
      inflammatory cells. To apply antiosteoclastic agents as another therapy for DRAO,
      we have to clarify the roles of those pathways in local osteoclastogenesis and/or
      osteoclast activation.

PMID- 11576945
TI  - Role of advanced glycation end products in adynamic bone disease in patients with
      diabetic nephropathy.
AB  - Adynamic bone disease and elevated serum levels of advanced glycation end
      products (AGEs) often are found in patients with renal failure caused by diabetic
      nephropathy. To clarify the role of AGEs in adynamic bone disease, we
      investigated the effect of these substances on cultured human osteoblasts and
      parathyroid cells. After 72 hours of incubation with AGEs-bovine serum albumin
      (BSA) (1,000 microgram/mL), there was significant inhibition of the synthesis of
      type I collagen and osteocalcin in response to stimulation with 10(-10) to 10(-8)
      M of 1,25-dihydroxycholecalciferol. In a human osteoblastic cell line (MG 63),
      AGEs-BSA did not affect human osteocalcin promoter activity. In human parathyroid
      cells, a receptor for AGEs was detected by reverse-transcriptase polymerase chain
      reaction. Incubation with AGEs-BSA for 48 hours significantly inhibited
      parathyroid hormone secretion in response to a low calcium concentration of 0.81
      mM (P < 0.01). In HEK-293 cells, expressing calcium-sensing receptors, the same
      AGE concentration caused a significant potentiation of the extracellular Ca(2+)
      induced-intracellular calcium concentration after 24 and 48 hours of incubation
      (P < 0.05 and P < 0.01). These data suggest that AGEs are involved in the
      pathogenesis of adynamic bone disease by inhibiting osteoblastic activity and by
      inhibiting parathyroid hormone secretion in response to hypocalcemia.

PMID- 11576946
TI  - Putative parathyroid tumor suppressor on 1p: independent molecular mechanisms of
      tumorigenesis from 11q allelic loss.
AB  - Multiple endocrine neoplasia type 1 (MEN1) gene was identified to be a tumor
      suppressor that encodes menin, playing an important role in the development of
      MEN1-associated tumors. Somatic MEN1 gene mutations also were detected in
      sporadic non-MEN1 endocrine tumors. Frequent loss of chromosomal arm 1p has been
      reported in parathyroid adenomas, suggesting the existence of putative tumor
      suppressor genes on 1p. In this study, we performed allelotyping of chromosomes
      1p and 11q on 60 sporadic parathyroid adenomas. Thirteen of 48 (27%) informative
      tumors had allelic loss on 1p, and 18 of 50 (36%) had allelic loss on 11q. Ten of
      18 tumors with 11q allelic loss successfully completed the sequence of the MEN1
      gene coding region and splice junctions, and 3 of 10 (30%) tumors had no somatic
      mutation, indicating that other putative tumor-suppressor genes on 11q may
      contribute to their tumorigenesis. Frequency of allelic losses on 1p was
      significantly higher in tumors without 11q allelic losses (7 of 11 informative
      tumors [64%]) than in tumors with 11q allelic losses (3 of 17 informative tumors
      [18%]) by chi-square test (P = 0.0131; chi-square = 6.152). These observations
      suggested that putative tumor-suppressor genes locate on 1p, and pathways of
      their tumorigenesis are independent from inactivation of tumor-suppressor genes
      on 11q.

PMID- 11576947
TI  - More than 1,000 cases of total parathyroidectomy with forearm autograft for renal
      hyperparathyroidism.
AB  - Between March 1981 and December 2000, we performed 1,053 total
      parathyroidectomies with forearm autograft for advanced renal hyperparathyroidism
      (HPT). Based on histopathologic and pathophysiologic investigations, surgical
      treatment should be considered when parathyroid glands show nodular hyperplasia.
      Measuring parathyroid volume by ultrasonography was useful to detect nodular
      glands and to determine surgical indications. The clinical effect of
      parathyroidectomy on the symptoms and biochemical variables was striking.
      Skeletal deformity, progressive bone loss, and vessel calcification leading to
      high mortality risk could not be alleviated by even successful surgery, however.
      To prevent cardiovascular complications, parathyroidectomy should be performed in
      the relatively early stage of renal HPT. Total parathyroidectomy with forearm
      autograft is a suitable procedure for renal HPT, especially in patients who
      require long-term hemodialysis. For surgeons, it is important to remove all
      parathyroid glands, including supernumerary glands, at the initial operation and
      to choose adequate parathyroid tissue for the autograft to prevent persistent and
      recurrent HPT. Although the risk of graft-dependent recurrent HPT is not
      negligible, enlarged transplanted parathyroid tissue can be removed easily and
      noninvasively from the forearm under local anesthesia. There is no risk of
      hypofunction of the autograft.

PMID- 11576948
TI  - Comparison of intact PTH assay and whole PTH assay in long-term dialysis
      patients.
AB  - Adynamic bone disease has become a major problem in long-term dialysis patients.
      It has been suggested that higher levels of parathyroid hormone (PTH) are needed
      to maintain normal bone turnover in uremia. PTH levels currently are evaluated
      routinely by intact PTH assay, which may detect inactive 7-84 PTH fragments as
      well as 1-84 PTH. We examined the efficacy of whole PTH assay, which detects 1-84
      PTH exclusively, in 99 nondiabetic patients on maintenance dialysis for more than
      10 years, without any residual renal function. PTH levels determined by whole PTH
      assay were lower than those determined by intact PTH assay in all cases. Serum
      markers of bone metabolism, such as serum activity of bone alkaline phosphatase,
      correlated well with whole PTH levels. Because 7-84 PTH has been shown to inhibit
      the effects of 1-84 PTH, the biologic activity of circulating PTH in uremic
      patients may be much lower than the values assayed by conventional intact PTH
      assay. Despite an attempt to correlate 1-84 PTH/7-84 PTH ratio with bone
      histology, we could find only 1 patient out of 99 with 1-84 PTH/7-84 PTH ratio
      less than 1, which has been suggested to be indicative of low turnover bone. A
      cutoff value of this ratio should be set in the future for patients with a long
      hemodialysis history, with various modes of medical therapy.

PMID- 11576949
TI  - Osteoprotegerin levels before and after renal transplantation.
AB  - Osteoprotegerin (OPG) is a newly identified glycoprotein that belongs to the
      tumor necrosis factor receptor superfamily and regulates bone mass by inhibiting
      osteoclastic bone resorption. The regulatory mechanism of OPG is still unclear
      after successful renal transplantation (RTX), however, resulting in resolution of
      uremia. The present study was designed to clarify the potential role of OPG in
      uremia and after RTX under immunosuppressive therapy. We evaluated circulating
      OPG levels by measuring them before and after RTX (postoperative days 2, 14, and
      28). Our protocol of immunosuppressive drugs was dual therapy using cyclosporine
      and steroids. Serum OPG was quantitated using enzyme-linked immunosorbent assay.
      After successful RTX, serum OPG levels decreased significantly on day 14 and day
      28 compared with the baseline level (P < 0.05). Creatinine clearance dramatically
      increased until day 14 and decreased thereafter. Serum OPG declines for the first
      2 weeks after RTX owing to functioning allograft and decreases again for the next
      2 weeks because of steroids and possible immunosuppressive agents.

PMID- 11576950
TI  - Cellular mechanisms in the development and progression of diabetic nephropathy:
      activation of the DAG-PKC-ERK pathway.
AB  - Diabetic nephropathy is characterized functionally by glomerular hyperfiltration
      and albuminuria and histologically by the expansion of glomerular mesangium. We
      and others have found that protein kinase C (PKC) is activated through an
      increase in de novo synthesis of diacylglycerol (DAG) from glucose in glomerular
      mesangial cells cultured under high glucose conditions and in glomeruli of
      diabetic rats. The activation of PKC could activate further various intracellular
      signal transduction systems, such as extracellular regulated kinase (ERK). The
      activation of the DAG-PKC-ERK pathway is considered to be one of the important
      molecular mechanisms of the development and progression of diabetic nephropathy.
      To prove this hypothesis, we examined whether the inhibition of the DAG-PKC-ERK
      pathway could prevent the development of glomerular dysfunction in diabetic
      animals. First, we found that thiazolidinedione compounds could inhibit PKC
      activation by activating DAG kinase. Thiazolidinedione compounds were able to
      prevent glomerular hyperfiltration, albuminuria, and excessive production of
      extracellular matrix proteins in glomeruli in streptozotocin-induced diabetic
      rats, a model for type 1 diabetes. Second, we tried to inhibit PKC directly by
      oral administration of PKC beta inhibitor. PKC beta inhibitor could prevent
      albuminuria and mesangial expansion in db/db mice, a model for type 2 diabetes.
      These results confirmed the importance of the activation of the DAG-PKC-ERK
      pathway in the development of glomerular dysfunction in diabetes.

PMID- 11576951
TI  - Association of transforming growth factor-beta1 T29C polymorphism with the
      progression of diabetic nephropathy.
AB  - Diabetes mellitus is a leading cause of end-stage renal disease in the Western
      world. Histologically, mesangial expansion with increased extracellular matrix
      protein is observed in patients with diabetic nephropathy. Because transforming
      growth factor (TGF)-beta promotes extracellular matrix production in response to
      high glucose, TGF-beta is considered to play a central role in the pathogenesis
      of diabetic nephropathy. We investigated the association of TGF-beta1 T29C
      polymorphism and the progression of diabetic nephropathy. Forty patients with
      type 2 diabetes mellitus were enrolled. All patients had had diabetes for more
      than 10 years. DNA was extracted from peripheral blood cells, and genotype was
      determined using real-time polymerase chain reaction method. Patients were
      classified into three groups according to genotype: TT, TC, and CC. Grade of
      diabetic nephropathy was determined using the amount of urinary excretion of
      albumin. Demographic characteristics of the patients with each genotype were not
      statistically different. No differences in the glycemic control and the mode of
      therapy were observed. Among patients with three genotypes, the severity of
      diabetic nephropathy was not statistically different. The patients with TT
      genotype tended to have a higher rate of progression of nephropathy; however, no
      statistically significant difference was observed among the three groups. Our
      results suggest that TGF-beta1 T29C polymorphism is not associated with the
      progression of diabetic nephropathy. Further studies are required to determine
      the exact role of this polymorphism in the progression of diabetic nephropathy.

PMID- 11576952
TI  - Renal insufficiency accelerates atherosclerosis in patients with type 2 diabetes
      mellitus.
AB  - Diabetes mellitus is a strong risk factor for the progression of atherosclerosis.
      In patients with chronic renal failure on hemodialysis, advanced atherosclerosis
      is reported to be present. We examined how renal insufficiency affects intima
      medial thickness (IMT) of the carotid and femoral arteries in patients with type
      2 diabetes mellitus. IMT was measured by B-mode ultrasonography in 115 patients
      with type 2 diabetes mellitus (65 men, 50 women; 58 +/- 13 years old). The IMT of
      the carotid and the femoral artery of patients with creatinine clearance less
      than 80 mL/min (n = 55) were significantly greater than those of patients with
      creatinine clearance 80 mL/min or greater (n = 60; P < 0.01 and P < 0.05). Linear
      regression analyses showed that there was a significant negative correlation
      between creatinine clearance and IMT of the carotid artery (r = -0.330; P <
      0.001) and femoral artery (r = -0.336; P < 0.001). Multiple regression analyses
      revealed that age and creatinine clearance significantly and independently
      affected the IMT of the carotid artery (R(2) = 0.176; P < 0.0001), and age,
      duration of diabetes, and smoking affected the IMT of the femoral artery (R(2) =
      0.287; P < 0.0001). These findings show that decreased renal function accelerates
      atherosclerosis in patients with type 2 diabetes mellitus and that chronic renal
      failure is a significant, independent risk factor for carotid atherosclerosis in
      these patients.

PMID- 11576953
TI  - A clinical trial in type 2 diabetic nephropathy.
AB  - A prospective, randomized, three-armed, double-blind, placebo-controlled clinical
      trial has been completed in 210 sites worldwide to determine whether the
      angiotensin II receptor blocker irbesartan or the calcium channel blocker
      amlodipine has a renoprotective effect in patients with overt type 2 diabetic
      nephropathy. A total of 1,715 subjects randomized during a 3-year period were
      followed a minimum of 2 years. The goal for all treatment groups was to achieve
      equivalent blood pressure control, with the blinded study drug (irbesartan,
      amlodipine, or placebo) as primary therapy with additional antihypertensive
      drugs, excluding angiotensin-converting enzyme inhibitors, calcium antagonists,
      and angiotensin II receptor antagonists, to achieve seated systolic blood
      pressure less than 135 mm Hg and diastolic blood pressure less than 85 mm Hg. The
      primary outcome was the combined endpoint of time to doubling of entry serum
      creatinine, end-stage renal disease, or death. Secondary outcomes included fatal
      and nonfatal cardiovascular events. A Clinical Management Committee monitored the
      conduct of the study. An Outcome Confirmation Committee classified all study
      outcome events in blinded fashion. An external Data Safety Monitoring Committee
      monitored unblinded data for interim safety and efficacy analyses of the study.
      Eligibility criteria included informed consent, age 30 to 70 years, adult-onset
      diabetes, hypertension, urine protein excretion greater than 900 mg/24 hours, and
      serum creatinine values of 90 to 265 micromol/L in women and 110 to 265
      micromol/L in men. Baseline characteristics were age, 59 +/- 8 years; body mass
      index, 31 +/- 7 kg/m(2); 67% male; 73% white, 14% black, and 13% other; duration
      of diabetes, 15 +/- 9 years; retinopathy, 66%; neuropathy, 48%; congestive heart
      failure, 7.5%; screening seated systolic blood pressure, 156 +/- 18 mm Hg, and
      diastolic blood pressure, 85 +/- 11 mm Hg; urine protein excretion, 4.0 +/- 3.5
      g/24 hours; serum creatinine, 150 +/- 53 micromol/L; serum potassium, 4.6 +/- 0.5
      mEq/L; total cholesterol, 229 +/- 58 mg/dL; and hemoglobin A(1c), 8.1 +/- 1.7%.
      This large-scale international trial should help define the clinical course and
      standards of care for hypertensive adults with type 2 diabetes mellitus and
      nephropathy. Results available on May 19, 2001, will help in defining the current
      controversy of the risks and benefits of blockade of the renin-angiotensin system
      versus calcium channel blockade versus standard antihypertensive therapy in this
      large patient population.

PMID- 11576954
TI  - Hemodialysis in diabetic patients.
AB  - Diabetic nephropathy is a leading cause of end-stage renal disease, and its
      prevalence and incidence vary greatly from country to country, being highest in
      the United States and Japan. In the United States, diabetic nephropathy accounts
      for approximately 40% of patients beginning renal replacement therapy. Type 2
      diabetes is the largest and fastest-growing single disease that requires dialytic
      therapy. Most patients succumb to cardiovascular causes, including coronary
      artery disease and myocardial infarction, sudden death, cardiac failure, and
      stroke. The survival from cardiovascular complications is relatively better in
      East Asian countries and to a lesser extent in Mediterranean countries compared
      with countries that traditionally have higher cardiovascular death rates.
      Peripheral vascular disease and sepsis contribute to increased morbidity and
      mortality. Amputation of limbs secondary to peripheral vascular disease in
      particular has adverse effects on rehabilitation. Asymptomatic hypoglycemia may
      develop in hemodialysis patients. Such hypoglycemia is not associated with a
      hormonal balance but is postulated to be due to blunted hormonal response to
      hypoglycemia. Diabetic muscle infarction is another rare complication
      attributable to diabetic microangiopathy; magnetic resonance imaging may help in
      the diagnosis. Risk factors for increased mortality include advanced age, poor
      glycemic control before starting dialysis, smoking, left ventricular hypertrophy,
      hypoalbuminemia, and neuropathy, in particular, autonomic dysfunction. In
      addition to adequate dialysis, it is advisable to achieve tight blood pressure
      control (at least <140/90 mm Hg and preferably much lower), better blood glucose
      control (hemoglobin A(1c), <7%), correction of nutritional status, and
      appropriate foot care.

PMID- 11576955
TI  - Peritoneal dialysis in diabetic patients.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease worldwide.
      Although death rates of diabetic patients on hemodialysis and peritoneal dialysis
      (PD) have decreased substantially, they remain higher than rates in nondiabetics
      on both modalities. PD offers equal or better survival than hemodialysis for
      younger diabetic patients during early years of dialysis. PD technique survival
      does not appear different between diabetic and nondiabetic patients but is
      inferior to hemodialysis technique survival. PD may accelerate changes in
      peritoneal membrane structure and function in diabetics. Peritonitis and
      conventional PD solutions containing high glucose and glucose degradation
      products are implicated in PD technique failure. Increased peritoneal expression
      of vascular endothelial growth factor and transforming growth factor-beta1 and
      excessive accumulation of advanced glycosylation end products may be involved in
      the progressive increase in membrane permeability, loss of ultrafiltration, and
      peritoneal fibrosis. Nonglucose PD solutions or solutions containing low glucose
      degradation products may prevent or delay alterations in peritoneal membrane
      structure and function in diabetic as well as nondiabetic patients during long
      term PD.

PMID- 11576956
TI  - Activation of protein kinase c-delta and c-epsilon by oxidative stress in early
      diabetic rat kidney.
AB  - Hyperglycemia-induced oxidative stress and protein kinase C (PKC) activation are
      implicated in the development and progression of diabetic nephropathy. Although
      PKC activation under hyperglycemia largely is related to an increase in de novo
      synthesis of diacylglycerol (DAG), activation of PKC can be regulated sensitively
      by oxidative stress. We investigated the expression and translocation of PKC
      isoforms in streptozotocin (STZ)-induced diabetic rat glomeruli and tubules and
      the effect of an antioxidant taurine. Experimental diabetes was induced by
      intravenous injection of 50 mg/kg of STZ. Two days after STZ, diabetic rats were
      assigned to one of two groups: untreated or treated with taurine 1% in drinking
      water. Four weeks after STZ, PKC isoforms were measured by Western blot analysis
      in the isolated glomeruli and tubules. DAG-dependent PKC isoforms PKC-alpha, PKC
      betaI, PKC-betaII, PKC-delta, and PKC-epsilon and DAG-independent PKC-zeta all
      were detected in control rat glomeruli and tubules. Streptozotocin increased
      plasma glucose from 167 +/- 11 mg/dL to 575 +/- 35 mg/dL (n = 9, P < 0.01) and
      lipid peroxidation from 1.9 +/- 0.2 nmol/mL to 4.2 +/- 0.6 nmol/mL (P < 0.05) and
      induced proteinuria. In diabetic glomeruli, membrane-associated PKC-delta and PKC
      epsilon content increased 47% and 57% above control, and membrane PKC-betaI
      content decreased to 67% of control. The membrane-associated PKC-alpha, PKC
      betaII, and PKC-zeta content were not influenced. Total PKC-delta (163%) and PKC
      epsilon (157%) increased significantly in diabetic tubules. Taurine prevented
      proteinuria and effectively inhibited alterations in PKC-delta and PKC-epsilon of
      diabetic glomeruli and tubules at dose-inhibiting lipid peroxidation but not
      hyperglycemia. These data suggest that PKC-delta and PKC-epsilon are sensitively
      activated by hyperglycemia-induced oxidative stress in diabetic rat kidney.

PMID- 11576957
TI  - Changes in body fat mass in male hemodialysis patients: a comparison between
      diabetics and nondiabetics.
AB  - Nutritional status is an important factor that affects morbidity and mortality of
      hemodialysis patients. We investigated 1-year changes in body fat mass of male
      patients undergoing hemodialysis (duration, 4.9 +/- 2.5 years). Fat mass of 217
      male patients (age 60 +/- 13 years) was measured by dual x-ray absorptiometry
      twice in a 1-year interval. The patients consisted of 70 with diabetes mellitus
      and 147 without diabetes. At the second measurement compared with the first, a
      significant decrease in fat mass was observed in diabetic patients (12.1 +/- 4.4
      kg versus 11.0 +/- 4.7 kg; P < 0.01); there were no significant changes in fat
      mass in nondiabetic patients (12.2 +/- 5.0 kg versus 11.9 +/- 4.9 kg; P = 0.15).
      Significant differences in percent fat mass changes per year were seen between
      diabetic and nondiabetic patients (P < 0.05). Protein catabolic rates of diabetic
      patients were significantly lower than those of nondiabetic patients (0.86 +/-
      0.18 g/kg/d versus 0.93 +/- 0.19 g/kg/d; P < 0.05). In all patients, there was a
      significant correlation between protein catabolic rates and percent fat mass
      changes per year (r = 0.15; P < 0.05). These results showed that body fat mass
      was decreased significantly in 1 year in male diabetic patients with maintenance
      hemodialysis, suggesting poorer nutritional status in these patients. Poor
      protein intake may be one of the risk factors for the decrease in fat mass. Dual
      x-ray absorptiometry assessment of fat mass changes is suggested as a useful
      method to examine clinically the nutritional status of hemodialysis patients.

PMID- 11576958
TI  - Outcomes of hemodiafiltration based on Japanese dialysis patient registry.
AB  - Effectiveness of various therapeutic modalities was analyzed among 1,196 patients
      entered in the registry of the Japanese Society for Dialysis Therapy who were on
      hemopurification therapy as of the end of 1998 and developed dialysis-related
      amyloidosis during 1999. In the investigation, the effectiveness of various
      hemopurification modalities on the dialysis-related amyloidosis was ranked as
      exacerbation, unchanged, or alleviation, so as to analyze the possible
      relationship between the hemopurification modality and its effectiveness. The
      analysis was performed using a logistic regression approach, and the results were
      shown as "the risk of a worse therapeutic ranking" among the hemopurification
      modalities. The smaller "the risk of a worse therapeutic effect" was, the more
      effective the treatment modality. When the risk of a worse therapeutic effect for
      the hemodialysis patients treated by a regular membrane was put at 1.0, the risk
      for hemodialysis patients using high-flux membrane was 0.489, the off-line
      hemodiafiltration risk was 0.117, the on-line hemodiafiltration risk was 0.013,
      and the risk of push/pull hemodiafiltration was 0.017. For hemodialysis with a
      beta(2)-microglobulin adsorption column, a low risk of 0.054 was found. The
      results indicated that hemodiafiltration therapy and simultaneous hemodialysis
      with beta(2)-microglobulin adsorption therapy were more effective treatment for
      dialysis-related amyloidosis.

PMID- 11576959
TI  - New dialysis membrane for removal of middle molecule uremic toxins.
AB  - Because ultrafiltration provides an alternative pass for removal of middle
      molecules from the bloodstream, high hydraulic permeability is necessary as well
      as high diffusive permeability. For this reason, polysulfone membrane became a
      clinically popular material as a dialysis membrane. The author tested one
      polysulfone dialyzer in vitro (aqueous/bovine plasma) with special interest in
      its internal filtration, ultrafiltration, and reverse filtration observed in one
      dialyzer for removing solutes. Results showed that with higher blood and
      dialysate flow rates, removal of middle molecules was increased as a result of
      the internal filtration. Module design is crucial for larger fluid exchange with
      internal filtration. Hemodialysis with internal filtration may be considered as a
      limited-scale on-line hemodiafiltration with no additional hardware, which may be
      possible with polysulfone or other high flux membranes when highly purified
      dialysate fluid is prepared.

PMID- 11576960
TI  - Programmed filtration, a new method for removing large molecules and regulating
      albumin leakage during hemodiafiltration treatment.
AB  - During hemodiafiltration (HDF) treatment for chronic renal failure patients,
      replacing large volumes using high-flux membranes with relatively large pores is
      preferred from the standpoint of enhancing the elimination of large molecules (10
      to 50 kd). Aggressive protein-permeable treatment often results in massive
      leakage of essential albumin, however, which may cause fatigue, hypotension, and
      a decrease in the plasma albumin concentration in some patients. During 5-hour
      conventional HDF treatment with the filtration rate or pressure set at constant
      values, fractional albumin loss in the dialysate was assayed, which revealed that
      the albumin concentration in the dialysate showed a maximum value in the
      beginning with a steep decline within 1 hour. Approximately 40% to 50% of the
      total amount of albumin leakage occurred during the first 30 minutes.
      Concomitantly the large molecules transferred into the pores by aggressive
      filtration during the beginning partially plugged the pores, resulting in a
      decrease in the permeability for beta(2)-microglobulin. From the standpoint of
      achieving the highest clearance for large molecules, while suppressing albumin
      leakage below the acceptable range, the optimal profiles for filtration
      conditions in HDF have been proposed, in which either the transmembrane pressure
      is regulated according to the sigmoid curve in the pressure control manner or the
      flow rate is set along the concave in the flow control manner. The profiles of
      pressure or flow as a function of time have been programmed and installed in a
      HDF machine to perform an optimal HDF treatment automatically. The new filtration
      methods gave significantly higher beta(2)-microglobulin removal and lower albumin
      leakage than conventional HDF methods with constant filtration.

PMID- 11576961
TI  - Exercise for intermittent claudication. Supervised programmes should be
      universally available.

PMID- 11576962
TI  - Screening for cancer in venous thromboembolic disease.

PMID- 11576963
TI  - Wrong biochemistry results.

PMID- 11576964
TI  - Monitoring the safety of over the counter drugs. We need a better way than
      spontaneous reports.

PMID- 11576965
TI  - Preventive home visits to elderly people. Their effectiveness cannot be judged by
      randomised controlled trials.

PMID- 11576966
TI  - England introduces star system for hospital trusts.

PMID- 11576967
TI  - Breast clinic director accused of bullying and incompetence.

PMID- 11576970
TI  - Belgium cuts antibiotic use by 12%.

PMID- 11576971
TI  - Delay in GMC hearing breached doctor's human rights.

PMID- 11576972
TI  - Fake cows help to reduce sleeping sickness and use of insecticides.

PMID- 11576975
TI  - China admits its AIDS crisis.

PMID- 11576976
TI  - India wakes up to threat of bioterrorism.

PMID- 11576977
TI  - Randomised controlled trial of specialist nurse intervention in heart failure.
AB  - OBJECTIVES: To determine whether specialist nurse intervention improves outcome
      in patients with chronic heart failure. DESIGN: Randomised controlled trial.
      SETTING: Acute medical admissions unit in a teaching hospital. PARTICIPANTS: 165
      patients admitted with heart failure due to left ventricular systolic
      dysfunction. The intervention started before discharge and continued thereafter
      with home visits for up to 1 year. MAIN OUTCOME MEASURES: Time to first event
      analysis of death from all causes or readmission to hospital with worsening heart
      failure. RESULTS: 31 patients (37%) in the intervention group died or were
      readmitted with heart failure compared with 45 (53%) in the usual care group
      (hazard ratio=0.61, 95% confidence interval 0.33 to 0.96). Compared with usual
      care, patients in the intervention group had fewer readmissions for any reason
      (86 v 114, P=0.018), fewer admissions for heart failure (19 v 45, P<0.001) and
      spent fewer days in hospital for heart failure (mean 3.43 v 7.46 days, P=0.0051).
      CONCLUSIONS: Specially trained nurses can improve the outcome of patients
      admitted to hospital with heart failure.

PMID- 11576979
TI  - Attitudes and training of research fellows in surgery: national questionnaire
      survey.

PMID- 11576980
TI  - Analysis of cord blood gas at delivery: questionnaire study of practice in the
      United Kingdom.

PMID- 11576978
TI  - Effectiveness of home based support for older people: systematic review and meta
      analysis.
AB  - OBJECTIVE: To evaluate the effectiveness of home visiting programmes that offer
      health promotion and preventive care to older people. DESIGN: Systematic review
      and meta-analysis of 15 studies of home visiting. PARTICIPANTS: older people
      living at home, including frail older people at risk of adverse outcomes. OUTCOME
      MEASURES: Mortality, admission to hospital, admission to institutional care,
      functional status, health status. RESULTS: Home visiting was associated with a
      significant reduction in mortality. The pooled odds ratio for eight studies that
      assessed mortality in members of the general elderly population was 0.76 (95%
      confidence interval 0.64 to 0.89). Five studies of home visiting to frail older
      people who were at risk of adverse outcomes also showed a significant reduction
      in mortality (0.72; 0.54 to 0.97). Home visiting was associated with a
      significant reduction in admissions to long term institutional care in members of
      the general elderly population (0.65; 0.46 to 0.91). For three studies of home
      visiting to frail, "at risk" older people, the pooled odds ratio was 0.55 (0.35
      to 0.88). Meta-analysis of six studies of home visiting to members of the general
      elderly population showed no significant reduction in admissions to hospital
      (odds ratio 0.95; 0.80 to 1.09). Three studies showed no significant effect on
      health (standardised effect size 0.06; -0.07 to 0.18). Four studies showed no
      effect on activities of daily living (0.05; -0.07 to 0.17). CONCLUSION: Home
      visits to older people can reduce mortality and admission to long term
      institutional care.

PMID- 11576981
TI  - Challenge of culture, conscience, and contract to general practitioners' care of
      their own health: qualitative study.
AB  - OBJECTIVE: To explore general practitioners' perceptions of the effects of their
      profession and training on their attitudes to illness in themselves and
      colleagues. DESIGN: Qualitative study using focus groups and in depth interviews.
      SETTING: Primary care in Northern Ireland. PARTICIPANTS: 27 general
      practitioners, including six recently appointed principals and six who also
      practised occupational medicine part time. MAIN OUTCOME MEASURES: Participants'
      views about their own and colleagues' health. RESULTS: Participants were
      concerned about the current level of illness within the profession. They
      described their need to portray a healthy image to both patients and colleagues.
      This hindered acknowledgement of personal illness and engaging in health
      screening. Embarrassment in adopting the role of a patient and concerns about
      confidentiality also influenced their reactions to personal illness. Doctors'
      attitudes can impede their access to appropriate health care for themselves,
      their families, and their colleagues. A sense of conscience towards patients and
      colleagues and the working arrangements of the practice were cited as reasons for
      working through illness and expecting colleagues to do likewise. CONCLUSIONS:
      General practitioners perceive that their professional position and training
      adversely influence their attitudes to illness in themselves and their
      colleagues. Organisational changes within general practice, including
      revalidation, must take account of barriers experienced by general practitioners
      in accessing health care. Medical education and culture should strive to promote
      appropriate self care among doctors.

PMID- 11576982
TI  - Science, medicine, and the future: Artificial limbs.

PMID- 11576983
TI  - ABC of the upper gastrointestinal tract: Oesophagus: heartburn.

PMID- 11576984
TI  - Raising standards in emergency relief: how useful are Sphere minimum standards
      for humanitarian assistance?

PMID- 11576985
TI  - Wrong SIGN, NICE mess: is national guidance distorting allocation of resources?

PMID- 11576986
TI  - Complexity, leadership, and management in healthcare organisations.

PMID- 11576987
TI  - Author's reply to criticism of study on benzodiazepines and risk of hip fracture.

PMID- 11576988
TI  - Journal should show balance, not bias, when reporting on PFI.

PMID- 11576989
TI  - Implementing clinical governance. Intellectual discussion would have been useful.

PMID- 11576990
TI  - Systematic reviews and Cochrane collaboration. Cochrane library is now available
      free to people working in NHS.

PMID- 11576991
TI  - Duodenal haematoma occurs in children with bicycle injuries.

PMID- 11576992
TI  - Doctors should not participate in executions.

PMID- 11576993
TI  - Plight of Afghan people must not be forgotten.

PMID- 11576996
TI  - Role of the high mobility group A proteins in human lipomas.
AB  - The HMGA family is comprised of four proteins: HMGA1a, HMGA1b, HMGA1c and HMGA2.
      The first three proteins are products of the same gene, HMGA1, generated through
      an alternative splicing mechanism. The HMGA proteins are involved in the
      regulation of chromatin structure and HMGA DNA-binding sites have been identified
      in functional regions of many gene promoters. Rearrangements of the HMGA2 gene
      have been frequently detected in human benign tumors of mesenchymal origin
      including lipomas. 12q13-15 chromosomal translocations involving the HMGA2 gene
      locus, account for these rearrangements. The HMGA proteins have three AT-hook
      domains and an acidic C-terminal tail. The HMGA2 modifications consist in the
      loss of the C-terminal tail and fusion with ectopic sequences. A pivotal role of
      the HMGA2 rearrangements in the process of lipomagenesis is suggested by
      experiments showing that transgenic mice carrying a truncated HMGA2 gene showed a
      giant phenotype together with abdominal/pelvic lipomatosis. As HMGA2 null mice
      showed a great reduction in fat tissue, a positive role of the HMGA2 gene in
      adipocytic cell proliferation is proposed. More recently, similar alterations of
      the HMGA1 gene have been described. As the block of the HMGA1 protein synthesis
      induces an increase in growth rate of the pre-adipocytic cell line 3T3-L1, we
      suggest a negative role of the HMGA1 proteins in adipocytic cell growth and,
      therefore, we propose that adipocytic cell growth derives from the balance of the
      HMGA1 and HMGA2 protein functions.

PMID- 11576997
TI  - Reduction of malignant phenotype of HEPG2 cell is associated with the expression
      of connexin 26 but not connexin 32.
AB  - Connexin (Cx) genes have a negative growth effect on tumour cells with certain
      specificity. However, it is not clear whether each Cx gene can act similarly in
      growth control. Hepatocytes normally express Cx26 and Cx32 as their major gap
      junction genes, but HepG2 cells, a hepatoma cell line, are deficient in gap
      junctional intercellular communication (GJIC) based on the down-regulation of
      Cx26 and aberrant localization of Cx32. In this study, we showed that some of the
      expressed Cx26 protein in HepG2 cells localized in the plasma membrane and
      contributed to recovery of GJIC, while the Cx32 protein remained localized in the
      cytoplasm. The Cx26-transfected clones showed a significantly slower growth in
      vivo as well as in vitro and reduced anchorage-independent growth ability
      compared with a mock-transfected clone. Cx26-transfected cells had more regular
      cell layers due to the re-establishment of the E-cadherin cell adhesion complex.
      E-cadherin expression following Cx26 transfection was induced. Cx26 expression
      simultaneously brought E-cadherin and beta-catenin proteins into the plasma
      membrane without any change in the expression level of beta-catenin protein.
      These results suggest that the expression of Cx26 contributes to negative growth
      control of HepG2 cells and the morphological change through the induction of E
      cadherin and subsequent formation of cell adhesion complex.

PMID- 11576998
TI  - Inhibition of apoptosis in rat hepatocytes treated with 'non-dioxin-like'
      polychlorinated biphenyls.
AB  - Polychlorinated biphenyls (PCBs) are among the most prominent persistent
      environmental pollutants exhibiting neurotoxic, teratogenic and tumour-promoting
      effects in experimental animals. 'Dioxin-like' properties have been assigned to a
      number of PCBs whereas other PCBs have been classified as 'non-dioxin-like'. Many
      of the latter congeners are inducers of cytochrome P450 (CYP) 2B1 and 2B2 similar
      to the liver tumour promoter phenobarbital. In contrast, 'dioxin-like' PCBs
      induce CYP1A isozymes, and other congeners have been classified as 'mixed-type'
      inducers. Inhibition of apoptosis of pre-neoplastic hepatocytes is thought to
      play a central role in tumour promotion in rat liver. We have used the inhibition
      of UV-induced apoptosis in rat hepatocytes in primary culture as an in vitro
      model for mechanistic studies on the inhibition of apoptosis. It could be shown
      that phenobarbital, and the 'non-dioxin-like' PCBs 28, 101 and 187 completely
      inhibit UV-induced apoptosis. The concentration-response curves and EC(50) values
      for this effect, however, were different from those of induction of CYP2B1/2B2
      catalysed 7-pentoxyresorufine O-dealkylase or CYP1A-catalysed 7-ethoxyresorufine
      O-deethylase activities. The PCBs and phenobarbital did not affect the
      spontaneous incidence of apoptotic nuclei. In conclusion, 'non-dioxin-like' PCBs
      are likely to promote liver carcinogenesis via the suppression of apoptosis. The
      signaling events in rat hepatocytes leading to induction of 2B1/2B2 activity by
      the compounds investigated are assumed to differ from those leading to inhibition
      of apoptosis.

PMID- 11576999
TI  - p53-independent apoptosis mediated by tachpyridine, an anti-cancer iron chelator.
AB  - Iron is involved in essential biochemical reactions ranging from respiration to
      DNA synthesis. Consequently, iron deprivation has been proposed as a strategy for
      inhibition of tumor cell growth. We recently described a novel iron chelator,
      tachypyridine [N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane],
      and demonstrated that it not only inhibited growth of cultured tumor cells, but
      was actively cytotoxic. Here we explore the mechanisms underlying tachpyridine
      cytotoxicity. Using several criteria, including time-lapse video microscopy, DNA
      staining and TUNEL assays, tachpyridine was shown to specifically induce
      apoptotic cell death. Further, unlike numerous cytotoxic chemotherapeutic drugs
      which induce apoptosis by activating p53-dependent pathways, tachpyridine
      mediated cell death did not require p53 activation. Although immunoblotting
      revealed rapid accumulation of p53 following treatment with tachpyridine,
      p21(WAF1) was not induced. Further, neither cytotoxicity nor apoptosis required
      p53. p53 null human lung cancer H1299 cells transfected with an ecdysone
      inducible p53 exhibited equivalent sensitivity to tachpyridine in the presence
      and absence of p53, demonstrating the lack of requirement for p53 in an isogenic
      cell system. Further, time-lapse video microscopy and TUNEL assays demonstrated
      that both p53 null and p53 wild-type cells underwent apoptotic cell death in
      response to tachpyridine. In addition, in 55 human cancer cell lines the mean
      GI(50) of tachpyridine in cells with mutant p53 was virtually identical to the
      GI(50) in cells with wild-type p53. These results demonstrate that tachpyridine
      initiates an apoptotic mode of cell death that does not require functional p53.
      Since over 50% of human tumors contain a functionally defective p53 that reduces
      sensitivity to commonly used chemotherapeutic agents, such as etoposide and
      cisplatin, the ability of tachpyridine to induce apoptosis independently of p53
      may offer an advantage in anti-tumor therapy.

PMID- 11577000
TI  - DNA hypermethylation is a mechanism for loss of expression of the HLA class I
      genes in human esophageal squamous cell carcinomas.
AB  - The three human leukocyte antigen (HLA) class I antigens, HLA-A, HLA-B and HLA-C,
      play important roles in the elimination of transformed cells by cytotoxic T
      cells. Frequent loss of expression of these antigens at the cell surface has been
      observed in many human cancers. Various mechanisms for post-transcriptional
      regulation have been proposed and tested but the molecular mechanisms for
      transcriptional regulation are not clear. We show by immunohistochemistry that
      the HLA class I antigens are absent in 26 of 29 (89%) samples of human esophageal
      squamous cell carcinomas (ESCC). Eleven of the 26 ESCC samples lost mRNA
      expression for at least one of the HLA genes, as shown by RT-PCR. DNA from the 29
      pairs of ESCC and neighboring normal epithelium were examined for CpG island
      hypermethylation, homozygous deletion, microsatellite instability (MSI) and loss
      of heterozygosity (LOH). DNA from normal epithelial tissues had no detectable
      methylation of the CpG islands of any of these gene loci. Thirteen of 29 ESCC
      samples (45%) exhibited methylation of one or more of the three HLA loci and six
      samples (21%) exhibited methylation of all three loci. The HLA-B gene locus was
      most frequently methylated (38%). HLA-B mRNA expression in an ESCC cell line,
      where HLA-B was hypermethylated and did not express mRNA, was activated after
      treatment with 5-aza-2'-deoxycytidine. Homozygous deletion of these three gene
      loci was not observed. Relatively low rates of LOH and MSI were observed for the
      microsatellite markers D6S306, D6S258, D6S273 and D6S1666, close to the HLA-A, -B
      and -C loci, although a high ratio of LOH was observed at a nearby locus
      (represented by the markers D6S1051 and D6S1560), where the tumor suppressor gene
      p21(Waf1) resides. A strong correlation between genetic alterations and mRNA
      inactivation was observed in the ESCC samples. Our results indicate that HLA
      class I gene expression was frequently down-regulated in ESCC at both the protein
      and mRNA levels and that hypermethylation of the promoter regions of the HLA-A, 
      B and -C genes is a major mechanism of transcriptional inactivation.

PMID- 11577001
TI  - Insulin-like growth factor-II renders LIM 2405 human colon cancer cells resistant
      to butyrate-induced apoptosis: a potential mechanism for colon cancer cell
      survival in vivo.
AB  - Butyrate has potent anti-tumorigenic effects on many colon cancer cell lines,
      including inhibition of growth and promotion of apoptosis in vitro. Nevertheless,
      despite the butyrate concentration in the colonic lumen being sufficient to
      result in the death of almost all cells in vitro, colon cancers still develop and
      grow in vivo, suggesting that cancer cells must develop mechanisms by which they
      escape the effects of butyrate observed in vitro. Insulin-like growth factor-II
      (IGF-II) is an autocrine growth factor in many colon cancer cells. The aim of
      this study was to determine whether IGF-II influences butyrate-mediated apoptosis
      in LIM 2405 human colon cancer cells. Butyrate and trichostatin A, both of which
      are histone deacetylase inhibitors although the latter is more specific, induced
      apoptosis as determined by floating cell counting, Hoechst 33258 staining, DNA
      laddering and a cell death detection ELISA. IGF-II inhibited the effects of both
      agents. Butyrate but not trichostatin A also induced LIM 2405 cell migration. In
      contrast to the above results, IGF-II enhanced butyrate-induced cell migration.
      Levels of IGF binding protein-3 (IGFBP-3), which may induce apoptosis by IGF
      dependent or -independent mechanisms, were increased by butyrate and trichostatin
      A; IGF-II augmented this effect. It is therefore unlikely that IGFBP-3 mediates
      butyrate-induced apoptosis. We suggest that IGF-II inhibits the pro-apoptotic
      effect of butyrate downstream of histone deacetylase inhibition. In contrast, IGF
      II promotes histone deacetylase-dependent IGFBP-3 expression and histone
      deacetylase-independent migration. IGF-II may promote tumour growth by mediating
      the development of resistance to the pro-apoptotic effects of butyrate.

PMID- 11577002
TI  - Bcl-2 overexpression attenuates resveratrol-induced apoptosis in U937 cells by
      inhibition of caspase-3 activity.
AB  - Resveratrol has been shown to induce anti-proliferation and apoptosis of human
      cancer cell lines. In the present study, we determined the effect of high
      intracellular levels of the anti-apoptosis protein Bcl-2 on caspase-3 activation,
      PLC-gamma1 degradation and cytochrome c release during resveratrol-induced
      apoptosis. For this, we used U937/vector and U937/Bcl-2 cells, which were
      generated by transfection of the cDNA of the Bcl-2 gene. As compared with
      U937/vector, U937/Bcl-2 cells exhibited a 4-fold greater expression of Bcl-2.
      Treatment with 60 or 100 microM resveratrol for 24 h produced morphological
      features of apoptosis and DNA fragmentation in U937/vector cells, respectively.
      This was associated with caspase-3 activation and PLC-gamma1 degradation. In
      contrast, resveratrol-induced caspase-3 activation and PLC-gamma1 degradation and
      apoptosis were significantly inhibited in U937/Bcl-2 cells. Bcl-2 overexpressing
      cells exhibited less cytochrome c release and sustained expression levels of the
      IAP proteins during resveratrol-induced apoptosis. In addition, these findings
      indicate that Bcl-2 inhibits resveratrol-induced apoptosis by a mechanism that
      interferes with cytochrome c release and activity of caspase-3 that is involved
      in the execution of apoptosis.

PMID- 11577003
TI  - Neoplastic transformation and tumorigenesis associated with overexpression of
      phospholipase D isozymes in cultured murine fibroblasts.
AB  - Phospholipase D (PLD) has been suggested to play an important role in a variety
      of cellular functions. PLD activity has been shown to be significantly elevated
      in many tumours and transformed cells, suggesting the possibility that PLD might
      be involved in tumorigenesis. In this study, we have established stable cell
      lines overexpressing PLD1 and PLD2 from fibroblast cells. These cells, but not
      control cells, showed altered growth properties and anchorage-independent growth
      in soft agar. Both PLD1 and PLD2 also induced an up-regulation of the activity of
      matrix metalloprotease-9 as detected by zymograms. Furthermore, both PLD1 and
      PLD2 transformants, but not vector-transfectants, induced undifferentiated
      sarcoma when transplanted into nude mice. Both PLD1- and PLD2-mediated cell cycle
      distributions in stable cell lines revealed an increased fraction of cells in the
      S phase compared with control cells. Interestingly, the level of cyclin D3
      protein, known as an activator of G(1) to S phase transition in the cell cycle,
      was aberrantly high in cells overexpressing PLD1 and PLD2 compared with control
      cells. These results suggest that overexpression of PLD isozymes may play an
      important role in neoplastic transformation.

PMID- 11577005
TI  - Red meat and colon cancer: dietary haem-induced colonic cytotoxicity and
      epithelial hyperproliferation are inhibited by calcium.
AB  - High intake of red meat is associated with increased colon cancer risk. We have
      shown earlier that this may be due to the high haem content of red meat, because
      dietary haem increased cytolytic activity of faecal water and colonic epithelial
      proliferation. Dietary calcium inhibits diet-induced epithelial
      hyperproliferation. Furthermore, it has been shown that supplemental calcium
      inhibited the recurrence of colorectal adenomas. Therefore, we studied whether
      dietary calcium phosphate can exert its protective effects by inhibiting the
      deleterious effects of haem. In vitro, calcium phosphate precipitated haem and
      inhibited the haem-induced cytotoxicity. Subsequently, rats were fed diets,
      differing in haem (0 or 1.3 micromol/g) and calcium phosphate content only (20 or
      180 micromol/g). Faeces were collected for biochemical analyses. Cytolytic
      activity of faecal water was determined from the degree of lysis of erythrocytes
      by faecal water. Colonic epithelial proliferation was measured in vivo using
      [(3)H]thymidine incorporation. In rats fed low calcium diets, dietary haem
      increased cytolytic activity of faecal water (98 +/- 1 versus 1 +/- 1%, P <
      0.001) and the concentration of cations in faeces (964 +/- 31 versus 254 +/- 20
      micromol/g), when compared with controls. This indicates that dietary haem
      increased colonic mucosal exposure to luminal irritants. Colonic epithelial
      proliferation was increased compared with controls (70 +/- 4 versus 48 +/- 8
      d.p.m./microg DNA, P < 0.001). This was accompanied by metabolism of the ingested
      haem and solubilization of haem compounds in the faecal water. A high calcium
      diet largely prevented this metabolism and solubilization. It also inhibited the
      haem-induced cytolytic activity of faecal water and increase in faecal cation
      concentration. In accordance, the haem-induced colonic epithelial
      hyperproliferation was prevented. We therefore suggest that dietary calcium
      phosphate acts as a chemopreventive agent in colon carcinogenesis by inhibiting
      the cytolytic and hyperproliferative effects of dietary haem.

PMID- 11577004
TI  - Wheat germ extract inhibits experimental colon carcinogenesis in F-344 rats.
AB  - It has been demonstrated for the first time that a wheat germ extract prevents
      colonic cancer in laboratory animals. Four-week-old inbred male F-344 rats were
      used in the study. Colon carcinogenesis has been induced by azoxymethane (AOM).
      Ten rats served as untreated controls (group 1). For the treatment of the animals
      in group 2, AOM was dissolved in physiologic saline and the animals were given
      three subcutaneous injections 1 week apart, 15 mg/kg body weight (b/w) each. In
      two additional groups Avemar (MSC), a fermented wheat germ extract standardized
      to 2,6-dimethoxy-p-benzoquinone was administered as a tentative chemo-preventive
      agent. MSC was dissolved in water and was given by gavage at a dose of 3 g/kg b/w
      once a day. In group 3, animals started to receive MSC 2 weeks prior to the first
      injection of AOM daily and continuously thereafter until they were killed 32
      weeks later. In group 4 the basal diet and MSC were administered only. At the end
      of the experiment all the rats were killed by exsanguination, the abdominal large
      vessels were cut under a light ether anesthesia and a complete autopsy was
      performed. Percentage of animals developing colon tumors and number of tumors per
      animals: group 1 - 0 and 0; group 2- 83.0 and 2.3; group 3 - 44.8 (P < 0.001) and
      1.3 (P < 0.004), group 4 - 0 and 0. All the tumors were of neoplastic nature also
      histologically. The numbers of the aberrant crypt foci (ACF) per area (cm(2)) in
      group 2 were 4.85 while in group 3 the ACF numbers were 2.03 only (P < 0.0001).

PMID- 11577006
TI  - COMT genotype, micronutrients in the folate metabolic pathway and breast cancer
      risk.
AB  - Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol
      estrogens (CEs), using S-adenosylmethionine (SAM) as a methyl donor. Several
      studies have indicated that the val108met COMT polymorphism, which results in a 3
      4-fold decrease in activity, is associated with increased breast cancer risk.
      Folate, whose intake levels have also been associated with breast cancer risk,
      and other micronutrients in the folate metabolic pathway influence levels of SAM
      and S-adenosylhomocysteine (SAH), a COMT inhibitor generated by the demethylation
      of SAM. Because these micronutrients have been shown to alter SAM and SAH levels,
      we hypothesized that they could also affect COMT-catalyzed CE methylation.
      Although measurements of SAM and SAH were not initially collected, a secondary
      analysis of data from two nested case-control studies was performed to examine
      whether serum levels of folate, vitamin B12 (B12), pyridoxal 5'-phosphate (PLP),
      cysteine and homocysteine, in conjunction with COMT genotype, were associated
      with breast cancer risk. COMT(HH) (high activity COMT homozygote) breast cancer
      cases had statistically significantly lower levels of homocysteine (P = 0.05) and
      cysteine (P = 0.04) and higher levels of PLP (P = 0.02) than COMT(HH) controls.
      In contrast, COMT(LL) (low activity COMT homozygote) cases had higher levels of
      homocysteine than COMT(LL) controls (P = 0.05). No associations were seen between
      B12, COMT genotype, and breast cancer risk. An increasing number of COMT(L)
      alleles was significantly associated with increased breast cancer risk in women
      with below median levels of folate (P(trend) = 0.05) or above median levels of
      homocysteine (P(trend) = 0.02). These findings are consistent with a role for
      certain folate pathway micronutrients in mediating the association between COMT
      genotype and breast cancer risk.

PMID- 11577007
TI  - Dietary genistin stimulates growth of estrogen-dependent breast cancer tumors
      similar to that observed with genistein.
AB  - The estrogenic soy isoflavone, genistein, stimulates growth of estrogen-dependent
      human breast cancer (MCF-7) cells in vivo. Genistin is the glycoside form of
      genistein and the predominant form found in plants. It is generally believed that
      genistin is metabolized to the aglycone genistein in the lower gut. However, it
      is unclear if the rate of metabolism of genistin to genistein is sufficient to
      produce a level of genistein capable of stimulating estrogen-dependent breast
      cancer cell growth. Our hypothesis was that dietary genistin would stimulate
      tumor growth similar to that observed with genistein in athymic mice. To test
      this hypothesis, genistin or genistein was fed to athymic mice containing
      xenografted estrogen-dependent breast tumors (MCF-7). Mice were fed either
      genistein at 750 p.p.m. (parts per milllion) or genistin at 1200 p.p.m., which
      provides equal molar concentrations of aglycone equivalents in both diets. Tumor
      size was measured weekly for 11 weeks. At completion of the study, half of the
      animals per treatment group were killed and tumors collected for evaluation of
      cellular proliferation and estrogen-responsive pS2 gene expression. Incorporation
      of bromo-deoxyuridine into cellular DNA was utilized as an indicator of cellular
      proliferation. Dietary genistin resulted in increased tumor growth, pS2
      expression and cellular proliferation similar to that observed with genistein.
      The remaining mice were switched to diets free of genistin and genistein. When
      mice were placed on isoflavone free diets, tumors regressed over a span of 9
      weeks. Next, we examined how effectively and where metabolism of genistin to
      genistein occurred in the digestive tract. We present evidence that demonstrates
      conversion of genistin to its aglycone form genistein begins in the mouth and
      then continues in the small intestine. Both human saliva and the intestinal cell
      free extract from mice converted genistin to genistein. In summary, the glycoside
      genistin, like the aglycone genistein, can stimulate estrogen-dependent breast
      cancer cell growth in vivo. Removal of genistin or genistein from the diet caused
      tumors to regress.

PMID- 11577008
TI  - Protective activity of butyrate on hydrogen peroxide-induced DNA damage in
      isolated human colonocytes and HT29 tumour cells.
AB  - Epidemiological studies support the involvement of short-chain fatty acids (SCFA)
      in colon physiology and the protective role of butyrate on colon carcinogenesis.
      Among the possible mechanisms by which butyrate may exert its anti
      carcinogenicity an antioxidant activity has been recently suggested. We
      investigated the effects of butyrate and mixtures of SCFA (butyrate, propionate
      and acetate) on DNA damage induced by H(2)O(2) in isolated human colonocytes and
      in two human colon tumour cell lines (HT29 and HT29 19A). Human colonocytes were
      isolated from endoscopically obtained samples and the DNA damage was assessed by
      the comet assay. H(2)O(2) induced DNA damage in normal colonocytes in a dose
      dependent manner which was statistically significant at concentrations over 10
      microM. At 15 microM H(2)O(2) DNA damage in HT29 and HT29 19A cells was
      significantly lower than that observed in normal colonocytes (P < 0.01). Pre
      incubation of the cells with physiological concentrations of butyrate (6.25 and
      12.5 mM) reduced H(2)O(2) (15 microM) induced damage by 33 and 51% in human
      colonocytes, 45 and 75% in HT29 and 30 and 80% in HT29 19A, respectively.
      Treatment of cells with a mixture of 25 mM acetate + 10.4 mM propionate + 6.25 mM
      butyrate did not induce DNA damage, while a mixture of 50 mM acetate + 20.8 mM
      propionate + 12.5 mM butyrate was weakly genotoxic only towards normal
      colonocytes. However, both mixtures were able to reduce the H(2)O(2)-induced DNA
      damage by about 50% in all cell types. The reported protective effect of butyrate
      might be important in pathogenetic mechanisms mediated by reactive oxygen
      species, and aids understanding of the apparent protection toward colorectal
      cancer exerted by dietary fibres, which enhance the butyrate bioavailability in
      the colonic mucosa.

PMID- 11577009
TI  - Dietary heterocyclic amines and microsatellite instability in colon
      adenocarcinomas.
AB  - Microsatellite instability (MSI) is now an accepted and important pathway in
      colon tumorigenesis, occurring in 10-15% of sporadic colon cancers and almost all
      hereditary nonpolyposis colon cancers. Little is known about possible
      environmental influences on MSI status in colon cancer. We conducted an
      epidemiological study of 276 colon cancer cases in Los Angeles County that was
      designed to determine the population prevalence of MSI(+) colon cancer and to
      identify environmental influences in the development of MSI(+) tumors. Our
      results support the cigarette smoking and MSI(+) association recently reported
      [Slattery,M.L., Curtin,K., Anderson,K. et al. (2000) J. Natl Cancer Inst., 92,
      1831-1836]. Risk of MSI(+) colon cancers increased with increasing dose (number
      of cigarettes per day) and increasing duration (years of smoking) of smoking.
      Compared with never-smokers, those who smoked 1-20 pack-years and >20 pack-years
      showed odds ratios of 1.39 and 1.64, respectively (P for trend = 0.03). In
      addition, our results show, for the first time, that after adjustment for
      cigarette smoking habits and red meat intake, patients with MSI(+) colon cancers
      had significantly higher dietary exposure to heterocyclic aromatic amines (HAA)
      as determined by two surrogates of high dietary HAA exposure: preference for well
      done red meat and high frequencies of certain cooking practices (frying,
      barbecuing, broiling and using meat drippings). The risk of MSI(+) colon cancer
      was increased 3-fold (smoking/red meat intake adjusted OR = 3.03, 95% CI = 1.06,
      8.63) among patients who preferred to eat red meat that was very well-done and
      was increased >2-fold (smoking/red meat adjusted OR = 2.33, 95% CI = 1.00, 5.25)
      among those who frequently fried/barbecued/broiled their meats or used meat
      drippings. The risk of MSI(+) colon cancer associated with cigarette smoking
      remained statistically significant after adjustment for high dietary HAA
      exposure. The significant association between cigarette smoking and dietary HAA
      with a specific subset of colon cancers may explain, at least in part,
      inconsistencies in results linking these two exposures to colon cancers. These
      results provide a potential mechanism of linking HAA exposure and cigarette
      smoking to a specific subset of colon cancers.

PMID- 11577010
TI  - Frequent allelic imbalance on chromosome 6 and 17 correlate with radiation
      induced neoplastic transformation of human breast epithelial cells.
AB  - The development of human breast cancer is a complex multi-step process that
      depends on various exogenous and endogenous factors that modulate the
      transformation of normal human breast epithelial cells into neoplastic ones.
      Using a spontaneously-immortalized human breast epithelial (MCF-10F) cell line,
      we have shown previously that radiation, in combination with estrogen, induces a
      stepwise neoplastic transformation of this cell line. In the present study, we
      investigate the incidence of microsatellite instability and loss of
      heterozygosity using a battery of markers on chromosomes 6 and 17, we correlate
      the genetic alteration with the malignant transformation of the MCF-10F cell line
      ranging from altered morphology to increase in proliferative rate, anchorage
      independent growth and tumorigenicity in nude mice. Microsatellite markers were
      selected from the hot spot regions (6q21-q27, 17p12-p13.3 and 17q12-q21) of both
      chromosomes. We found that the frequency of allelic imbalance occurs at the
      different stages of tumor progression with a range of 21 to 50% depending on the
      marker studied. The relatively high rate of allele imbalance at all these loci
      suggests the presence and inactivation of one or more tumor suppressor genes in
      these regions. Thus, the present data will be useful for systematic studies to
      identify the cellular and molecular changes associated with radiation-induced
      breast carcinogenesis.

PMID- 11577011
TI  - Immunohistochemical localization and semi-quantitation of hepatic tamoxifen-DNA
      adducts in rats exposed orally to tamoxifen.
AB  - Administration of tamoxifen (TAM) has been shown to induce hepatocellular
      carcinogenesis and TAM-DNA adduct formation in rat liver. Here we present TAM-DNA
      adduct localization and semi-quantitation in hepatic tissue of rats by
      immunohistochemical staining followed by image analysis. We have also used a
      quantitative immunoassay to provide a validation for the immunohistochemical
      values. Rats were fed diets containing 0, 5, 50, 150 or 500 p.p.m. TAM for 45
      weeks. Serial sections of paraffin-embedded liver were stained for TAM-DNA
      adducts using a polyclonal TAM-DNA antiserum. Subsequently, visualization of TAM
      DNA adducts was performed by peroxidase-conjugated secondary antibody-mediated
      signal amplification using biotinyl tyramide followed by streptavidin-alkaline
      phosphatase and fast red. Semi-quantitation of nuclear color intensity was
      achieved with an Automated Cellular Imaging System (ACIS), with a detection limit
      of 1 TAM-DNA adduct per 10(7) nt for these experiments. In parenchymal cells of
      liver sections from TAM-exposed animals a dose-dependent increase in nuclear
      staining was observed by ACIS and the TAM-DNA adduct levels determined by ACIS
      were validated in liver DNA by quantitative chemiluminescence immunoassay (CIA).
      Comparison of semi-quantitative values determined by ACIS with quantitative
      values determined by CIA showed a strong correlation (r = 0.924) between the two
      methods. At 45 weeks of TAM exposure the liver cytoplasm contained placental
      glutathione S-transferase (GST-p)-positive foci, as indicated by new fuchsin
      staining. Staining of serial sections revealed a relative lack of TAM-DNA adducts
      within these enzyme-altered foci. In addition, some GST-p foci contained islands
      of cells that did not stain for GST-p but were positive for TAM-DNA adduct
      formation. This study validates the use of ACIS for TAM-DNA adduct formation and
      demonstrates that steady-state TAM-DNA adduct levels observed in livers of rats
      chronically fed TAM for several months increase in relation to dose. In addition,
      unlike the normal surrounding liver, preneoplastic GST-p-positive foci have
      virtually no TAM-DNA adducts.

PMID- 11577012
TI  - Lack of effect of 94 GHz radio frequency radiation exposure in an animal model of
      skin carcinogenesis.
AB  - Although there is no evidence that electromagnetic energy in the radio frequency
      radiation (RFR) band is mutagenic, there have been suggestions that RFR energy
      might serve as either a promoter or co-promoter in some animal models of
      carcinogenesis. Recent developments in electromagnetic technology have resulted
      in the manufacture of RFR sources capable of generating frequencies in the
      millimeter wavelength (MMW) range (30-300 GHz). Because absorption of MMW energy
      occurs in the skin, it is to be expected that long-term detrimental health
      effects, if any, would most likely be manifest in the skin. In this study we
      investigated whether a single (1.0 W/cm(2) for 10 s) or repeated (2
      exposures/week for 12 weeks, 333 mW/cm(2) for 10 s) exposure to 94 GHz RFR serves
      as a promoter or co-promoter in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced
      SENCAR mouse model of skin carcinogenesis. Neither paradigm of MMW exposure
      significantly affected papilloma development, as evidenced by a lack of effect on
      tumor incidence and multiplicity. There was also no evidence that MMW exposure
      served as a co-promoter in DMBA-induced animals repeatedly treated with 12-O
      tetradecanoylphorbol 13-acetate. Therefore, we conclude that exposure to 94 GHz
      RFR under these conditions does not promote or co-promote papilloma development
      in this animal model of skin carcinogenesis.

PMID- 11577013
TI  - Suppression of spontaneous and hydrogen peroxide-induced mutagenesis by the
      antioxidant ascorbate in mismatch repair-deficient human colon cancer cells.
AB  - Genomic instability associated with deficiencies in mismatch repair (MMR) plays a
      critical role in tumorigenesis. Here we have investigated the contribution of
      oxidative damage to this instability in MMR-defective cells. Treatment with
      H(2)O(2) produced less cytotoxicity in MMR-deficient cells than in those
      proficient in MMR, supporting a role for MMR in the recognition and/or processing
      of oxidative damage. Additionally, growth of MMR-defective cells in the presence
      of the antioxidant ascorbate (500 microM) reduced the spontaneous mutation rate
      at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus by up to 50%
      and reduced microsatellite instability by 30%. Induction of HPRT mutants by
      exogenously added H(2)O(2) was also significantly suppressed by ascorbate.
      Collectively, these results suggest that (i) oxidative damage contributes
      significantly to the spontaneous mutator phenotype in MMR-defective cells, (ii)
      this damage may select for MMR-deficient cells due to their increased resistance
      to cell killing and (iii) dietary antioxidants may help to suppress the mutator
      phenotype and resulting carcinogenesis in individuals with compromised MMR.

PMID- 11577014
TI  - Promoter methylation of the DNA repair gene MGMT in astrocytomas is frequently
      associated with G:C --> A:T mutations of the TP53 tumor suppressor gene.
AB  - O(6)-Methylguanine-DNA methyltransferase (MGMT) is a repair protein that
      specifically removes promutagenic alkyl groups from the O(6) position of guanine
      in DNA. Repair of O(6)-alkylguanine adducts by tumour cells has been implicated
      in drug resistance since it reduces the cytotoxicity of alkylating
      chemotherapeutic agents. We assessed promoter methylation of the MGMT gene in
      astrocytic brain tumours by methylation-specific PCR. MGMT promoter methylation
      was detected in 26 of 54 (48%) low-grade diffuse astrocytomas (WHO grade II) and
      in 12 of 16 (75%) of secondary glioblastomas (WHO grade IV) that had progressed
      from low-grade astrocytomas. The frequency of MGMT methylation was significantly
      lower in primary (de novo) glioblastomas (13 of 36, 36%, P = 0.0155). The
      majority of low-grade astrocytomas with MGMT methylation (24/26, 92%) contained a
      TP53 mutation, whereas only 11 out of 28 (39%) cases without MGMT methylation
      carried a TP53 mutation (P < 0.0001). Furthermore, G:C --> A:T transition
      mutations at CpG sites were significantly more frequent in low-grade astrocytomas
      with MGMT methylation (15/26, 58%) than in those without (3/28, 11%, P = 0.0004).
      These results suggest that loss of MGMT expression as a result of promoter
      methylation, which frequently occurs at an early stage in the pathway leading to
      secondary glioblastomas, appears to be associated with increased frequency of
      TP53 mutations, in particular G:C --> A:T transitions.

PMID- 11577015
TI  - Intestinal microflora plays a crucial role in the genotoxicity of the cooked food
      mutagen 2-amino-3-methylimidazo [4,5-f]quinoline.
AB  - We investigated the impact of the intestinal microflora on the genotoxicity of 2
      amino-3-methylimidazo[4,5-f] quinoline (IQ), a mutagenic/carcinogenic
      heterocyclic amine commonly found in fried meats and fish. In parallel, we also
      examined the effect of the microflora on the protective effect of glucotropaeolin
      (GT), a glucosinolate contained in cruciferous vegetables, towards IQ-induced
      genotoxic effect. Conventional (NF), human flora associated (HFA) and germ free
      (GF) rats were treated either with 90 mg/kg IQ alone, 150 mg/kg GT alone or a
      combination of the two by gavage and DNA damage was determined in liver and colon
      cells using the alkaline single cell gel electrophoresis (SCGE) or comet assay.
      IQ caused a significant effect in both organs of all groups. However, DNA damage
      was most pronounced in NF animals. In colon cells, DNA migration was 6-fold more
      in IQ-exposed rats as compared with untreated controls. The effect measured with
      liver cells was similar. In comparison to NF rats, in HFA rats, tail length of
      the comets was 22 and 53% lower in liver and colon cells, respectively.
      Significantly weaker effects were seen in GF animals (66 and 75% lower damage in
      hepatocytes and colonocytes, respectively, than in NF animals). Pretreatment with
      GT led to a complete reduction of IQ-induced DNA damage regardless of the
      microbial status of the animals. In addition, a moderate decrease in spontaneous
      DNA damage was seen in animals that received GT alone. Our results show that the
      microflora has a strong impact on the genotoxic effects of IQ. We conclude that
      the alkaline SCGE assay with rats harbouring different flora opens new
      possibilities to investigate the role of intestinal bacteria on health risks
      caused by dietary carcinogens.

PMID- 11577016
TI  - Lovastatin-induced E2F-1 modulation and its effect on prostate cancer cell death.
AB  - Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitor, induces growth arrest in a variety of cancer cell lines. Its mechanism
      of action, however, has not been completely elucidated. E2F-1 is thought to act
      as an oncogene and a tumour suppressor, with its action probably dependent upon
      the cellular context. We have shown in this study that transcriptional regulation
      and proteasomal degradation of E2F-1 are critical regulatory events in lovastatin
      induced cell death. Accompanying this is a reduction in the E2F-1-regulated
      expression of cell cycle genes such as c-myc, cyclin D1, cyclin A and cyclin B1.
      Cell cycle analysis demonstrated that the accumulation of apoptotic cells was
      preceded by a progressive decrease in the S-phase cell population in response to
      lovastatin. Although expression of E2F-1 was reduced in three prostate cancer
      cell lines-PC-3, LNCaP and DU-145-the p21 and p27 protein levels were not
      increased in all the cell lines treated, suggesting that increase in p21 and p27
      protein expression per se is not responsible for lovastatin-mediated down
      regulation of E2F-1. The subsequent apoptotic death of these cells in the
      presence of lovastatin can be prevented by forced ectopic expression of E2F-1.
      Taken together, these facts imply that E2F-1 is the target of an HMG-CoA
      inhibitor and critical cell death mediator in prostate cancer cells.

PMID- 11577018
TI  - When the thyroid speaks, the heart listens.

PMID- 11577019
TI  - Vascular smooth muscle calcium channels: could "T" be a target?

PMID- 11577020
TI  - Smoking-induced vascular disease: a new twist on an old theme.

PMID- 11577021
TI  - Integrins in vascular development.
AB  - In recent years, there has been a sustained interest in vascularization
      processes. Much, if not all, of the work has included the concept of new vessel
      morphogenesis. Surprisingly, most of the work has not addressed developmental
      mechanisms directly, but rather as an offshoot of a disease process, wound
      healing process, or from the perspective of inducing vessels in an ischemic site.
      One theme has dominated the various studies on capillary or endothelial tube
      morphogenesis-integrin-mediated cell behavior. Integrin biology impacts virtually
      every known step of nascent vessel formation. In this review article, we
      attempted to summarize key findings from the viewpoint of developmental
      biologists/morphologists. We also attempted to summarize and contrast data
      obtained using integrin gene ablation approaches in mice with other experimental
      systems. It is hoped this review will provide a distinct cell biological
      perspective to vascular scientists from the clinical, molecular, and tissue
      engineering communities.

PMID- 11577022
TI  - Constitutive and inducible expression of Cyp1a1 and Cyp1b1 in vascular smooth
      muscle cells: role of the Ahr bHLH/PAS transcription factor.
AB  - Ahr is a ligand-activated bHLH/PAS transcription factor involved in cytochrome
      P450 (CYP) gene regulation and murine susceptibility to atherogenic stimuli. The
      present studies were conducted to examine constitutive and inducible expression
      of Cyp1a1 and Cyp1b1 in vascular smooth muscle cells (VSMCs) from Ahr(+/+) and
      Ahr(-/-) mice. Cyp1a1 mRNA was not expressed constitutively in VSMCs irrespective
      of Ahr phenotype. Although Cyp1a1 was inducible in Ahr(+/+) by 3 micromol/L
      benzo(a)pyrene, a known hydrocarbon inducer, the protein was uninducible. In
      contrast, Cyp1b1 mRNA and protein were expressed under constitutive and inducible
      conditions irrespective of Ahr phenotype or growth status. CYP-encoded aryl
      hydrocarbon hydroxylase activity was higher in Ahr(-/-) VSMCs under constitutive
      conditions and induced by benzo(a)pyrene in Ahr(+/+) and Ahr(-/-) VSMCs. CYP
      expression was influenced by mitogenic status, because randomly cycling cells
      consistently exhibited higher levels than growth-arrested counterparts.
      Actinomycin D (2 microgram/mL) or cycloheximide (10 micromol/L) did not inhibit
      constitutive or hydrocarbon-inducible aryl hydrocarbon hydroxylase activity in
      VSMCs. These data indicate that in murine VSMCs, expression of Cyp1al and Cyp1b1
      is differentially influenced by Ahr phenotype and mitogenic status, with patterns
      that may dictate inherent susceptibility to atherogenic stimuli.

PMID- 11577023
TI  - Thrombin suppresses endothelial nitric oxide synthase and upregulates endothelin
      converting enzyme-1 expression by distinct pathways: role of Rho/ROCK and mitogen
      activated protein kinase.
AB  - An imbalance of nitric oxide and endothelin plays an important role in
      cardiovascular disease. Thrombin exerts profound effects on endothelial function.
      The present study investigated the molecular mechanisms by which thrombin
      regulates endothelial nitric oxide synthase (eNOS) and endothelin-converting
      enzyme (ECE)-1 expression in human endothelial cells. Incubation of human
      umbilical vein endothelial cells with thrombin (0.01 to 4 U/mL) for 15 to 24
      hours markedly downregulated eNOS and increased ECE-1 protein level in a dose
      dependent manner. Thrombin also decreased eNOS mRNA and increased ECE-1 mRNA
      level. In mRNA stability assay, thrombin shortened the half-life of eNOS mRNA but
      not that of ECE-1 mRNA. Activation of protease-activated receptor 1 by the
      agonist (SFLLRN, 10 to 100 micromol/L) had no effect on eNOS expression but
      increased ECE-1 level as thrombin. Thrombin activated Rho A and extracellular
      signal-regulated kinase (ERK)1 and ERK2. Inhibition of Rho A by C3 exoenzyme (20
      microgram/mL) and ROCK by Y-27632 (10 micromol/L) prevented the downregulation of
      eNOS expression by thrombin. Y-27632 also prevented the reduction in NOS activity
      induced by prolonged incubation with thrombin. On the other hand, inhibition of
      ERK1 and ERK2 activation by PD98059 (50 micromol/L) prevented the upregulation of
      ECE-1 expression by thrombin as well as the increase in ECE activity and ET-1
      accumulation in the medium. Treatment of rat aorta with thrombin overnight
      impaired endothelium-dependent relaxations but not endothelium-independent
      relaxations. Thus, thrombin suppresses eNOS and upregulates ECE-1 expression via
      Rho/ROCK and ERK pathway, respectively. These effects of thrombin may be
      important for endothelial dysfunction in cardiovascular disease, particularly
      during acute coronary episodes.

PMID- 11577024
TI  - Regulation of thyroid hormone receptor isoforms in physiological and pathological
      cardiac hypertrophy.
AB  - Physiological and pathological cardiac hypertrophy have directionally opposite
      changes in transcription of thyroid hormone (TH)-responsive genes, including
      alpha- and beta-myosin heavy chain (MyHC) and sarcoplasmic reticulum Ca(2+)
      ATPase (SERCA), and TH treatment can reverse molecular and functional
      abnormalities in pathological hypertrophy, such as pressure overload. These
      findings suggest relative hypothyroidism in pathological hypertrophy, but serum
      levels of TH are usually normal. We studied the regulation of TH receptors (TRs)
      beta1, alpha1, and alpha2 in pathological and physiological rat cardiac
      hypertrophy models with hypothyroid- and hyperthyroid-like changes in the TH
      target genes, alpha- and beta-MyHC and SERCA. All 3 TR subtypes in myocytes were
      downregulated in 2 hypertrophy models with a hypothyroid-like mRNA phenotype,
      phenylephrine in culture and pressure overload in vivo. Myocyte TRbeta1 was
      upregulated in models with a hyperthyroid-like phenotype, TH (triiodothyronine,
      T3), in culture and exercise in vivo. In myocyte culture, TR overexpression, or
      excess T3, reversed the effects of phenylephrine on TH-responsive mRNAs and
      promoters. In addition, TR cotransfection and treatment with the TRbeta1
      selective agonist GC-1 suggested different functional coupling of the TR
      isoforms, TRbeta1 to transcription of beta-MyHC, SERCA, and TRbeta1, and TRalpha1
      to alpha-MyHC transcription and increased myocyte size. We conclude that TR
      isoforms have distinct regulation and function in rat cardiac myocytes. Changes
      in myocyte TR levels can explain in part the characteristic molecular phenotypes
      in physiological and pathological cardiac hypertrophy.

PMID- 11577025
TI  - Upregulation of functional beta(3)-adrenergic receptor in the failing canine
      myocardium.
AB  - Altered expression and functional responses to cardiac beta(3)-adrenergic
      receptors (ARs) may contribute to progressive cardiac dysfunction in heart
      failure (CHF). We compared myocyte beta(3)-AR mRNA and protein levels and myocyte
      contractile, [Ca(2+)](i) transient, and Ca(2+) current (I(Ca,L)) responses to BRL
      37344 (BRL, 10(-8) mol/L), a selective beta(3)-AR agonist, in 9 instrumented dogs
      before and after pacing-induced CHF. Myocytes were isolated from left ventricular
      myocardium biopsy tissues. Using reverse transcription-polymerase chain reaction,
      we detected beta(3)-AR mRNA from myocyte total RNA in each animal. Using a cloned
      canine beta(3)-AR cDNA probe and myocyte poly A(+) RNA, we detected a single band
      about 3.4 kb in normal and CHF myocytes. beta(3)-AR protein was detected by
      Western blot. beta(3)-AR mRNA and protein levels were significantly greater in
      CHF myocytes than in normal myocytes. Importantly, these changes were associated
      with enhanced beta(3)-AR-mediated negative modulation on myocyte contractile
      response and [Ca(2+)](i) regulation. Compared with normal myocytes, CHF myocytes
      had much greater decreases in the velocity of shortening and relengthening with
      BRL accompanied by larger reductions in the peak systolic [Ca(2+)](i) transient
      and I(Ca,L). These responses were not modified by pretreating myocytes with
      metoprolol (a beta(1)-AR antagonist) or nadolol (a beta(1)- and beta(2)-AR
      antagonist), but were nearly prevented by bupranolol or L-748,337 (beta(3)-AR
      antagonists). We conclude that in dogs with pacing-induced CHF, beta(3)-AR gene
      expression and protein levels are upregulated, and the functional response to
      beta(3)-AR stimulation is increased. This may contribute to progression of
      cardiac dysfunction in CHF.

PMID- 11577026
TI  - Mechanisms of L-type Ca(2+) current downregulation in rat atrial myocytes during
      heart failure.
AB  - Downregulation of the L-type Ca(2+) current (I(Ca)) is an important determinant
      of the electrical remodeling of diseased atria. Using a rat model of heart
      failure (HF) due to ischemic cardiopathy, we studied I(Ca) in isolated left
      atrial myocytes with the whole-cell patch-clamp technique and biochemical assays.
      I(Ca) density was markedly reduced (1.7+/-0.1 pA/pF) compared with sham-operated
      rats (S) (4.1+/-0.2 pA/pF), but its gating properties were unchanged. Calcium
      channel alpha(1C)-subunit quantities were not significantly different between S
      and HF. The beta-adrenergic agonist isoproterenol (1 micromol/L) had far greater
      stimulatory effects on I(Ca) in HF than in S (2.5- versus 1-fold), thereby
      suppressing the difference in current density. Dialyzing cells with 100
      micromol/L cAMP or pretreating them with the phosphatase inhibitor okadaic acid
      also increased I(Ca) and suppressed the difference in density between S and HF.
      Intracellular cAMP content was reduced more in HF than in S. The
      phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine had a greater effect on
      I(Ca) in HF than in S (76.0+/-11.2% versus 15.8+/-21.2%), whereas the inhibitory
      effect of atrial natriuretic peptide on I(Ca) was more important in S than in HF
      (54.1+/-4.8% versus 24.3+/-8.8%). Cyclic GMP extruded from HF myocytes was
      enhanced compared with S (55.8+/-8.0 versus 6.2+/-4.0 pmol. mL(-1)). Thus, I(Ca)
      downregulation in atrial myocytes from rats with heart failure is caused by
      changes in basal cAMP-dependent regulation of the current and is associated with
      increased response to catecholamines.

PMID- 11577027
TI  - Potentiation of Ca(2+) release by cADP-ribose in the heart is mediated by
      enhanced SR Ca(2+) uptake into the sarcoplasmic reticulum.
AB  - cADP-Ribose (cADPR) is a novel endogenous messenger that is believed to mobilize
      Ca(2+) from ryanodine-sensitive Ca(2+) stores. Despite intense research, the
      precise mechanism of action of cADPR remains uncertain, and experimental findings
      are contradictory. To elucidate the mechanism of cADPR action, we performed
      confocal Ca(2+) imaging in saponin-permeabilized rat ventricular myocytes.
      Exposure of the cells to cADPR resulted in a slow (>2 minutes) and steady
      increase in the frequency of Ca(2+) sparks. These effects on local release events
      were accompanied by a significant increase in sarcoplasmic reticulum (SR) Ca(2+)
      content. In comparison, sensitization of ryanodine receptors (RyRs) by caffeine,
      a true RyR agonist, caused a rapid (<1 second) and transient potentiation of
      Ca(2+) sparks followed by a decrease in SR Ca(2+) content. When the increase in
      the SR load was prevented by partial inhibition of the SR Ca(2+) with
      thapsigargin, cADPR failed to produce any increase in sparking activity. cADPR
      had no significant impact on activity of single cardiac RyRs incorporated into
      lipid bilayers. However, it caused a significant increase in the rate of Ca(2+)
      uptake by cardiac SR microsomes. Our results suggest that the primary target of
      cADPR is the SR Ca(2+) uptake mechanism. Potentiation of Ca(2+) release by cADPR
      is mediated by increased accumulation of Ca(2+) in the SR and subsequent luminal
      Ca(2+)-dependent activation of RyRs.

PMID- 11577028
TI  - Impaired cardiac functional reserve and left ventricular hypertrophy in adult
      sheep after prenatal dexamethasone exposure.
AB  - We have shown that exposure of pregnant ewes to dexamethasone (11.5 mg/d for 2
      days) at 27 days of gestation (term, 150 days) led to increased blood pressure
      and cardiac output in adult offspring. In this study, we hypothesized that
      dexamethasone-induced hypertension is associated with left ventricular
      hypertrophy and a reduced cardiac functional reserve (CO(max-0)). Six control
      animals (group C) and five dexamethasone-exposed animals (group D) were volume
      loaded with Hemaccel until the wedge pressure was 13 mm Hg (baseline). The wedge
      pressure was held constant during an infusion of dobutamine at incremental doses
      (0.4 to 12 microgram/kg/min) while blood pressure and cardiac output were
      measured. The same protocol was repeated in each animal 5 days later under mild
      general anesthesia (1.5% isoflurane), when transthoracic echocardiography (M
      mode) was obtained. Group D showed a reduced CO(max-0) in response to dobutamine
      during both conscious (89+/-22 versus 150+/-25 mL/kg/min in control; P<0.01) and
      anesthetized states (91+/-38 versus 156+/-56 mL/kg/min in control; P<0.05).
      Reduced CO(max-0) in group D was associated with higher left ventricular mass
      index compared with group C (2.6+/-0.67 versus 1.8+/-0.51 g/kg; P<0.05). In
      addition, group D showed a reduced cardiac contractility reserve (FS(max-0)) in
      response to dobutamine (21+/-22% versus 54+/-34% in group C; P<0.05). An impaired
      cardiac functional reserve in group D was associated with increased left
      ventricular type I collagen content. In conclusion, brief prenatal exposure to
      dexamethasone led to the development of hypertension, left ventricular
      hypertrophy, and reduced cardiac functional reserve in adult life.

PMID- 11577029
TI  - Differential expression of T- and L-type voltage-dependent calcium channels in
      renal resistance vessels.
AB  - The distribution of voltage-dependent calcium channels in kidney pre- and
      postglomerular resistance vessels was determined at the molecular and functional
      levels. Reverse transcription-polymerase chain reaction analysis of
      microdissected rat preglomerular vessels and cultured smooth muscle cells showed
      coexpression of mRNAs for T-type subunits (Ca(V)3.1, Ca(V)3.2) and for an L-type
      subunit (Ca(V)1.2). The same expression pattern was observed in juxtamedullary
      efferent arterioles and outer medullary vasa recta. No calcium channel messages
      were detected in cortical efferent arterioles. Ca(V)1.2 protein was demonstrated
      by immunochemical labeling of rat preglomerular vasculature and juxtamedullary
      efferent arterioles and vasa recta. Cortical efferent arterioles were not
      immunopositive. Recordings of intracellular calcium concentration with digital
      fluorescence imaging microscopy showed a significant increase of calcium in
      response to K(+) (100 mmol/L) in isolated afferent arterioles (140+/-25%) and in
      juxtamedullary efferent arterioles (118+/-21%). These calcium responses were
      attenuated by the L-type antagonist calciseptine and by the T-type antagonist
      mibefradil. Intracellular calcium increased in response to K(+) in cortical
      efferent arterioles (21+/-9%). Mibefradil and nickel concentration dependently
      blocked K(+)-induced contraction of perfused rabbit afferent arterioles.
      Calciseptine blocked the contraction mediated by K(+) (EC(50) 8x10(-14)). S-(-)
      Bay K 8644 had no effect on vascular diameter in the afferent arteriole. We
      conclude that voltage-dependent L- and T-type calcium channels are expressed and
      of functional significance in renal cortical preglomerular vessels, in
      juxtamedullary efferent arterioles, and in outer medullary vasa recta, but not in
      cortical efferent arterioles.

PMID- 11577030
TI  - Interpretation of transcript profiling.

PMID- 11577031
TI  - Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic
      lesion development and stability.
AB  - Interleukin (IL)-18 is the interferon-gamma-inducing factor and has other
      proinflammatory properties. The precise role of IL-18 in immunoinflammatory
      diseases remains poorly understood. In this study, we show that in vivo
      electrotransfer of an expression-plasmid DNA encoding for murine IL-18 binding
      protein (BP) (the endogenous inhibitor of IL-18) prevents fatty streak
      development in the thoracic aorta of apoE knockout mice and slows progression of
      advanced atherosclerotic plaques in the aortic sinus. More importantly,
      transfection with the IL-18BP plasmid induces profound changes in plaque
      composition (decrease in macrophage, T cell, cell death, and lipid content and
      increase in smooth muscle cell and collagen content) leading to a stable plaque
      phenotype. These results identify for the first time a critical role for IL-18/IL
      18BP regulation in atherosclerosis and suggest a potential role for IL-18
      inhibitors in reduction of plaque development/progression and promotion of plaque
      stability. The full text of this article is available at
      http://www.circresaha.org.

PMID- 11577034
TI  - Is it ethical to lie to secure hospital admission? Yes: Lying is sometimes in the
      patient's best interests.

PMID- 11577035
TI  - Is it ethical to lie to secure hospital admission? No: Lying undermines the
      practice of medicine.

PMID- 11577036
TI  - Health care without harm: an ethical imperative. A consensus statement from
      Biomedical Ethicists in Support of Environmentally Sound Healthcare Practices.

PMID- 11577037
TI  - The poor health of farm workers.

PMID- 11577038
TI  - The unhealthy alliance between academia and corporate America.

PMID- 11577040
TI  - It's beginning to look a lot like Christmas.

PMID- 11577042
TI  - Sound surgeons.

PMID- 11577044
TI  - Cervical cancer in the developing world.

PMID- 11577047
TI  - Rape is not violence masquerading as sex.

PMID- 11577048
TI  - Data correction.

PMID- 11577049
TI  - Role conflicts of physicians and their family members: rules but no rulebook.
AB  - OBJECTIVES: To elucidate the difficulties physicians have when a family member
      becomes ill and to elicit their underlying causes. DESIGN: Using a key informant
      technique, we solicited chairs of family medicine departments for their
      experiences with the health care provided to seriously ill family members. We
      then conducted in-depth, semistructured telephone interviews that were then
      transcribed, coded, and labeled for themes. SUBJECTS: 8 senior family physicians
      whose parents had experienced a serious illness within the past 5 years. All of
      the subjects reflected on experiences stemming from their fathers' illness.
      RESULTS: These physicians faced competing expectations: at an internal level,
      those of their ideal role in their family and their ideal professional identity;
      and at an external level, those originating from other family members and from
      other physicians. Reconciling these conflicting expectations was made more
      difficult by what they deemed to be suboptimal circumstances of the modern health
      care system. CONCLUSIONS: Conflicting rules of appropriate conduct, compounded by
      the inadequacies of modern health care, make the role of physician-family member
      especially challenging. The medical profession needs a clearer, more trenchant
      understanding of this role.

PMID- 11577050
TI  - Reliability of bimanual pelvic examinations performed in emergency departments.
AB  - OBJECTIVE: To test the reliability of bimanual pelvic examinations performed in
      emergency departments by emergency medicine physicians. DESIGN: Prospective
      observational study; 2 examiners each recorded various pelvic examination
      findings on 186 patients. SETTING: A private university hospital and a public
      county hospital staffed by attending emergency medicine physicians who share an
      emergency medicine residency program. SUBJECTS: Senior resident (3rd or 4th year)
      and attending emergency physicians. MAIN OUTCOME MEASURES: Percentage of
      agreement and percentage of positive agreement for cervical motion tenderness,
      uterine tenderness, adnexal tenderness, adnexal mass, and uterine size (within 2
      cm). RESULTS: The agreement ranged between 71% and 84%, but the percentage of
      positive agreement was much lower, ranging from 17% to 33%. Agreement for uterine
      size, within 2 cm, was 60%. CONCLUSION: The findings of bimanual pelvic
      examinations performed by emergency physicians in an emergency department have
      poor interexaminer reliability.

PMID- 11577053
TI  - Hyperlipidemia: Part 1. Evaluation and dietary management.

PMID- 11577054
TI  - Addressing the religious and spiritual needs of dying patients.

PMID- 11577055
TI  - An evidence-based approach to managing seizures associated with fever in
      children.

PMID- 11577056
TI  - Sponsorship, authorship, and accountability.

PMID- 11577057
TI  - Who should know about our genetic makeup and why?

PMID- 11577058
TI  - The Stark II regulations: an analysis.

PMID- 11577061
TI  - Are cyclooxygenase 2 inhibitors free of gastrointestinal side effects?

PMID- 11577062
TI  - Hypnosis and relaxation therapies.

PMID- 11577063
TI  - Discriminating positively: preferential acceptance of minorities may be good for
      society.

PMID- 11577064
TI  - Cutaneous melanoma: learning to see.

PMID- 11577065
TI  - Myth: an elevated leukocyte count distinguishes septic arthritis from less
      serious causes of hip pain.

PMID- 11577066
TI  - Immigrant women's health: Infectious diseases - Part 2.

PMID- 11577067
TI  - In the patient's best interest? Revisiting sexual autonomy and sterilization of
      the developmentally disabled.

PMID- 11577069
TI  - Caring for the dying: why is it so hard for physicians?

PMID- 11577070
TI  - Confronting death.

PMID- 11577071
TI  - Regulation of mitochondrial carbamoyl-phosphate synthetase 1 activity by active
      site fatty acylation.
AB  - In addition to its role in reversible membrane localization of signal-transducing
      proteins, protein fatty acylation could play a role in the regulation of
      mitochondrial metabolism. Previous studies have shown that several acylated
      proteins exist in mitochondria isolated from COS-7 cells and rat liver. Here, a
      prominent fatty-acylated 165-kDa protein from rat liver mitochondria was
      identified as carbamoyl-phosphate synthetase 1 (CPS 1). Covalently attached
      palmitate was linked to CPS 1 via a thioester bond resulting in an inhibition of
      CPS 1 activity at physiological concentrations of palmitoyl-CoA. This inhibition
      corresponds to irreversible inactivation of CPS 1 and occurred in a time- and
      concentration-dependent manner. Fatty acylation of CPS 1 was prevented by
      preincubation with N-ethylmaleimide and 5'-p-fluorosulfonylbenzoyladenosine, an
      ATP analog that reacts with CPS 1 active site cysteine residues. Our results
      suggest that fatty acylation of CPS 1 is specific for long-chain fatty acyl-CoA
      and very likely occurs on at least one of the essential cysteine residues
      inhibiting the catalytic activity of CPS 1. Inhibition of CPS 1 by long-chain
      fatty acyl-CoAs could reduce amino acid degradation and urea secretion, thereby
      contributing to nitrogen sparing during starvation.

PMID- 11577072
TI  - Hypoxia-induced regulation of MAPK phosphatase-1 as identified by subtractive
      suppression hybridization and cDNA microarray analysis.
AB  - Subtractive suppression hybridization was used to generate a cDNA library
      enriched in cDNA sequences corresponding to mRNA species that are specifically up
      regulated by hypoxia (6 h, 1% O(2)) in the oxygen-responsive pheochromocytoma
      cell line. The dual specificity protein-tyrosine phosphatase MAPK phosphatase-1
      (MKP-1) was highly represented in this library. Clones were arrayed on glass
      slides to create a hypoxia-specific cDNA microarray chip. Microarray, northern
      blot, and western blot analyses confirmed that MKP-1 mRNA and protein levels were
      up-regulated by hypoxia by approximately 8-fold. The magnitude of the effect of
      hypoxia on MKP-1 was approximately equal to that induced by KCl depolarization
      and much larger than the effects of either epidermal growth factor or nerve
      growth factor on MKP-1 mRNA levels. In contrast to the calcium-dependent
      induction of MKP-1 by KCl depolarization, the effect of hypoxia on MKP-1
      persisted under calcium-free conditions. Cobalt and deferoxamine also increased
      MKP-1 mRNA levels, suggesting that hypoxia-inducible factor proteins may play a
      role in the regulation of MKP-1 by hypoxia. Pretreatment of cells with SB203580,
      which inhibits p38 kinase activity, significantly reduced the hypoxia-induced
      increase in MKP-1 RNA levels. Thus, hypoxia robustly increases MKP-1 levels, at
      least in part through a p38 kinase-mediated mechanism.

PMID- 11577073
TI  - Characterization of single-stranded DNA-binding proteins from Mycobacteria. The
      carboxyl-terminal of domain of SSB is essential for stable association with its
      cognate RecA protein.
AB  - Single-stranded DNA-binding proteins (SSB) play an important role in most aspects
      of DNA metabolism including DNA replication, repair, and recombination. We report
      here the identification and characterization of SSB proteins of Mycobacterium
      smegmatis and Mycobacterium tuberculosis. Sequence comparison of M. smegmatis SSB
      revealed that it is homologous to M. tuberculosis SSB, except for a small spacer
      connecting the larger amino-terminal domain with the extreme carboxyl-terminal
      tail. The purified SSB proteins of mycobacteria bound single-stranded DNA with
      high affinity, and the association and dissociation constants were similar to
      that of the prototype SSB. The proteolytic signatures of free and bound forms of
      SSB proteins disclosed that DNA binding was associated with structural changes at
      the carboxyl-terminal domain. Significantly, SSB proteins from mycobacteria
      displayed high affinity for cognate RecA, whereas Escherichia coli SSB did not
      under comparable experimental conditions. Accordingly, SSB and RecA were
      coimmunoprecipitated from cell lysates, further supporting an interaction between
      these proteins in vivo. The carboxyl-terminal domain of M. smegmatis SSB, which
      is not essential for interaction with ssDNA, is the site of binding of its
      cognate RecA. These studies provide the first evidence for stable association of
      eubacterial SSB proteins with their cognate RecA, suggesting that these two
      proteins might function together during DNA repair and/or recombination.

PMID- 11577074
TI  - The proteasome participates in degradation of mutant alpha 1-antitrypsin Z in the
      endoplasmic reticulum of hepatoma-derived hepatocytes.
AB  - Because retention of mutant alpha(1)-antitrypsin (alpha(1)-AT) Z in the
      endoplasmic reticulum (ER) is associated with liver disease in alpha(1)-AT
      deficient individuals, the mechanism by which this aggregated glycoprotein is
      degraded has received considerable attention. In previous studies using stable
      transfected human fibroblast cell lines and a cell-free microsomal translocation
      system, we found evidence for involvement of the proteasome in degradation of
      alpha(1)-ATZ (Qu, D., Teckman, J. H., Omura, S., and Perlmutter, D. H. (1996) J.
      Biol. Chem. 271, 22791-22795). In more recent studies, Cabral et al. (Cabral, C.
      M., Choudhury, P., Liu, Y., and Sifers, R. N. (2000) J. Biol. Chem. 275, 25015
      25022) found that degradation of alpha(1)-ATZ in a stable transfected murine
      hepatoma cell line was inhibited by tyrosine phosphatase inhibitors, but not by
      the proteasomal inhibitor lactacystin and concluded that the proteasome was only
      involved in ER degradation of alpha(1)-ATZ in nonhepatocytic cell types or in
      cell types with levels of alpha(1)-AT expression that are substantial lower than
      that which occurs in hepatocytes. To examine this important issue in further
      detail, in this study we established rat and murine hepatoma cell lines with
      constitutive and inducible expression of alpha(1)-ATZ. In each of these cell
      lines degradation of alpha(1)-ATZ was inhibited by lactacystin, MG132,
      epoxomicin, and clasto-lactacystin beta-lactone. Using the inducible expression
      system to regulate the relative level of alpha(1)-ATZ expression, we found that
      lactacystin had a similar inhibitory effect on degradation of alpha(1)-ATZ at
      high and low levels of alpha(1)-AT expression. Although there is substantial
      evidence that other mechanisms contribute to ER degradation of alpha(1)-ATZ, the
      data reported here indicate that the proteasome plays an important role in many
      cell types including hepatocytes.

PMID- 11577075
TI  - The matrix attachment region-binding protein SATB1 interacts with multiple
      elements within the gp91phox promoter and is down-regulated during myeloid
      differentiation.
AB  - The gp91(phox) gene encodes a component of the respiratory burst NADPH oxidase
      complex and is highly expressed in mature myeloid cells. The transcriptional
      repressor CCAAT displacement protein binds to at least five sites within the
      proximal gp91(phox) promoter and represses expression prior to terminal phagocyte
      differentiation. The DNA binding activity of CCAAT displacement protein decreases
      during terminal phagocyte differentiation, thus permitting the binding of
      transcriptional activators and induction of gp91(phox) expression. We report here
      that the matrix attachment region-binding protein SATB1 interacts with at least
      seven sites within the -1542 to +12-base pair gp91(phox) promoter. Four
      additional binding sites for CCAAT displacement protein were also identified.
      Furthermore, the most proximal SATB1-binding site within the gp91(phox) promoter
      binds specifically to the nuclear matrix fraction in vitro. SATB1 expression is
      down-regulated during terminal myeloid cell differentiation, coincident with
      induction of gp91(phox) expression. Transient transfection assays demonstrate
      that a SATB1-binding site derived from the gp91(phox) promoter represses promoter
      activity in cells expressing SATB1. These findings underscore the importance of
      transcriptional repression in the regulation of gp91(phox) expression and reveal
      a candidate myeloid cell target gene for SATB1, a factor previously found to be
      essential for T cell development.

PMID- 11577076
TI  - Mimic of photocycle by a protein folding reaction in photoactive yellow protein.
AB  - The blue light receptor photoactive yellow protein (PYP) displays rhodopsin-like
      photochemistry based on the trans to cis photoisomerization of its p-coumaric
      acid chromophore. Here, we report that protein refolding from the acid-denatured
      state of PYP mimics the last photocycle transition in PYP. This implies a direct
      link between transient protein unfolding and photosensory signal transduction. We
      utilize this link to study general issues in protein folding. Chromophore trans
      to cis photoisomerization in the acid-denatured state strongly decelerates
      refolding, and converts the pH dependence of the barrier for refolding from
      linear to nonlinear. We propose transition state movement to explain this
      phenomenon. The cis chromophore significantly stabilizes the acid-denatured
      state, but acidification of PYP results in the accumulation of the acid-denatured
      state containing a trans chromophore. This provides a clear example of kinetic
      control in a protein unfolding reaction. These results demonstrate the power of
      PYP as a light-triggered model system to study protein folding.

PMID- 11577077
TI  - Topoisomerase II poisoning by ICRF-193.
AB  - Antineoplastic bis(dioxopiperazine)s, such as meso-2,3-bis(2,6-dioxopiperazin-4
      yl)butane (ICRF-193), are widely believed to be only catalytic inhibitors of
      topoisomerase II. However, topoisomerase inhibitors have little or no
      antineoplastic activity unless they are topoisomerase poisons, a special subclass
      of topoisomerase-targeting drugs that stabilize topoisomerase-DNA strand passing
      intermediates and thus cause the topoisomerase to become a cytotoxic DNA-damaging
      agent. Here we report that ICRF-193 is a very significant topoisomerase II
      poison. Detection of topoisomerase II poisoning by ICRF-193 required the use of a
      chaotropic protein denaturant in the topoisomerase poisoning assays. ICRF-193
      caused dose-dependent cross-linking of human topoisomerase IIbeta to DNA and
      stimulated topoisomerase IIbeta-mediated DNA cleavage at specific sites on (32)P
      end-labeled DNA. Human topoisomerase IIalpha-mediated DNA cleavage was stimulated
      to a lesser extent by ICRF-193. In vivo experiments with MCF-7 cells also showed
      the requirement of a chaotropic protein denaturant in the assays and selectivity
      for the beta-isozyme of human topoisomerase II. Studies with two topoisomerase
      IIbeta-negative cell model systems confirmed significant topoisomerase II
      poisoning by ICRF-193 in the wild type cells and were consistent with beta
      isozyme selectivity. Common use of only the detergent, SDS, in assays may have
      led to failure to detect topoisomerase II poisoning by ICRF-193 in earlier
      studies.

PMID- 11577078
TI  - Role of the PHTH module in protein substrate recognition by Bruton's
      agammaglobulinemia tyrosine kinase.
AB  - Defects in Bruton's tyrosine kinase (Btk) are responsible for X chromosome-linked
      agammaglobulinemia in patients. Mutations in each of the structural domains of
      Btk have been detected in patients, yet a mechanistic explanation for most of
      these mutant phenotypes is lacking. To understand the possible role of the unique
      pleckstrin homology and Tec homology (PHTH) module of Btk, we have compared the
      enzymatic properties of full-length Btk and a Btk mutant lacking the PHTH module
      (BtkDeltaPHTH). Here we show that Btk and BtkDeltaPHTH have similar basal
      catalytic activity but very different abilities to recognize protein substrates.
      Furthermore, the catalytic domain of Btk is inactive, in contrast to the
      catalytic domain of the prototypical Src tyrosine kinase that retains full
      catalytic ability. These data suggest that the PHTH module plays an important
      role in protein substrate recognition, that Btk and Src likely have different
      interdomain organizations and regulations, and that alterations in substrate
      recognition might play a role in X chromosome-linked agammaglobulinemia.

PMID- 11577079
TI  - The sequence-specific DNA binding of NF-kappa B is reversibly regulated by the
      automodification reaction of poly (ADP-ribose) polymerase 1.
AB  - Recent studies suggest that the synthesis of protein-bound ADP-ribose polymers
      catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1) regulates eucaryotic gene
      expression, including the NF-kappaB-dependent pathway. Here, we report the
      molecular mechanism by which PARP-1 activates the sequence-specific binding of NF
      kappaB to its oligodeoxynucleotide. We co-incubated pure recombinant human PARP-1
      and the p50 subunit of NF-kappaB (NF-kappaB-p50) in the presence or absence of
      betaNAD+ in vitro. Electrophoretic mobility shift assays showed that, when PARP-1
      was present, NF-kappaB-p50 DNA binding was dependent on the presence of betaNAD+.
      DNA binding by NF-kappaB-p50 was not efficient in the absence of betaNAD+. In
      fact, the binding was not efficient in the presence of 3-aminobenzamide (3-AB)
      either. Thus, we conclude that NF-kappaB-p50 DNA binding is protein-poly(ADP
      ribosyl)ation dependent. Co-immunoprecipitation and immunoblot analysis revealed
      that PARP-1 physically interacts with NF-kappaB-p50 with high specificity in the
      absence of betaNAD+. Because NF-kB-p50 was not an efficient covalent target for
      poly(ADP-ribosyl)ation, our results are consistent with the conclusion that the
      auto-poly(ADP-ribosyl)ation reaction catalyzed by PARP-1 facilitates the binding
      of NF-kappaB-p50 to its DNA by inhibiting the specific protein.protein
      interactions between NF-kappaB-p50 and PARP-1. We also report the activation of
      NF-kappaB DNA binding by the automodification reaction of PARP-1 in cultured HeLa
      cells following exposure to H(2)O(2). In these experiments, preincubation of HeLa
      cells with 3-AB, prior to oxidative damage, strongly inhibited NF-kappaB
      activation in vivo as well.

PMID- 11577080
TI  - Phosphorylation of Ser2078 modulates the Notch2 function in 32D cell
      differentiation.
AB  - Notch signaling is involved in the regulation of many cell fate determination
      events in both embryonic development and adult tissue homeostasis. We previously
      demonstrated that Notch1 and Notch2 molecules inhibit myeloid differentiation in
      a cytokine-specific manner and that the Notch cytokine response domain is
      necessary for this functional specificity. We have now investigated the putative
      role of phosphorylation in the activity of Notch in response to cytokine signals.
      Our results show that the granulocyte colony-stimulating factor (G-CSF)
      stimulation of 32D cells expressing the intracellular Notch2 protein induces
      phosphorylation at specific sites of this molecule, rendering the molecule
      inactive and permitting differentiation of these cells. In contrast, when cells
      are stimulated with granulocyte macrophage colony-stimulating factor (GM-CSF),
      intracellular notch2 is not phosphorylated at these residues and differentiation
      is inhibited. We also show that deletion of the Ser/Thr-rich region between amino
      acids 2067 and 2099 abrogates G-CSF-induced phosphorylation and results in a
      molecule that inhibits differentiation in response to either G-CSF or GM-CSF. Our
      results further indicate that Ser(2078) is a critical residue for phosphorylation
      and modulation of Notch2 activity in the context of G-CSF-induced differentiation
      of 32D cells.

PMID- 11577081
TI  - Contrasting effects of IG20 and its splice isoforms, MADD and DENN-SV, on tumor
      necrosis factor alpha-induced apoptosis and activation of caspase-8 and -3.
AB  - We identified a novel cDNA (IG20) that is homologous to cDNAs encoding a protein
      differentially expressed in normal and neoplastic cells (DENN-SV) and human MADD
      (MAPK-activating death domain-containing protein). Furthermore, we show that the
      above variants most likely result from alternative splicing of a single gene.
      Functional analyses of these variants in permanently transfected HeLa cells
      revealed that IG20 and DENN-SV render them more susceptible or resistant to tumor
      necrosis factor alpha (TNF-alpha)-induced apoptosis, respectively. All variants
      tested could interact with TNF receptor 1 and activate ERK and nuclear factor
      kappaB. However, relative to control cells, only cells expressing IG20 showed
      enhanced TNF-alpha-induced activation of caspase-8 and -3, whereas cells
      expressing DENN-SV showed either reduced or no caspase activation. Transfection
      of these cells with a cDNA encoding CrmA maximally inhibited apoptosis in HeLa
      IG20 cells. Our results show that IG20 can promote TNF-alpha-induced apoptosis
      and activation of caspase-8 and -3 and suggest that it may play a novel role in
      the regulation of the pleiotropic effects of TNF-alpha through alternative
      splicing.

PMID- 11577082
TI  - Novel role for RNA-binding protein CUGBP2 in mammalian RNA editing. CUGBP2
      modulates C to U editing of apolipoprotein B mRNA by interacting with apobec-1
      and ACF, the apobec-1 complementation factor.
AB  - Mammalian apolipoprotein B (apoB) mRNA editing is mediated by a multicomponent
      holoenzyme containing apobec-1 and ACF. We have now identified CUGBP2, a 54-kDa
      RNA-binding protein, as a component of this holoenzyme. CUGBP2 and ACF co
      fractionate in bovine liver S-100 extracts, and addition of recombinant apobec-1
      leads to assembly of a holoenzyme. Immunodepletion of CUGBP2 co-precipitates ACF,
      and these proteins co-localize the nucleus of transfected cells, suggesting that
      CUGBP2 and ACF are bound in vivo. CUGBP2 binds apoB RNA, specifically an AU-rich
      sequence located immediately upstream of the edited cytidine. ApoB RNA from McA
      cells, bound to CUGBP2, was more extensively edited than the unbound fraction.
      However, addition of recombinant CUGBP2 to a reconstituted system demonstrated a
      dose-dependent inhibition of C to U RNA editing, which was rescued with either
      apobec-1 or ACF. Antisense CUGBP2 knockout increased endogenous apoB RNA editing,
      whereas antisense knockout of either apobec-1 or ACF expression eliminated apoB
      RNA editing, establishing the absolute requirement of these components of the
      core enzyme. These data suggest that CUGBP2 plays a role in apoB mRNA editing by
      forming a regulatory complex with the three components of the minimal editing
      enzyme, apobec-1, ACF, and apoB RNA.

PMID- 11577083
TI  - Dual mode recognition of two isoacceptor tRNAs by mammalian mitochondrial seryl
      tRNA synthetase.
AB  - Animal mitochondrial translation systems contain two serine tRNAs, corresponding
      to the codons AGY (Y = U and C) and UCN (N = U, C, A, and G), each possessing an
      unusual secondary structure; tRNA(GCU)(Ser) (for AGY) lacks the entire D arm,
      whereas tRNA(UGA)(Ser) (for UCN) has an unusual cloverleaf configuration. We
      previously demonstrated that a single bovine mitochondrial seryl-tRNA synthetase
      (mt SerRS) recognizes these topologically distinct isoacceptors having no common
      sequence or structure. Recombinant mt SerRS clearly footprinted at the TPsiC loop
      of each isoacceptor, and kinetic studies revealed that mt SerRS specifically
      recognized the TPsiC loop sequence in each isoacceptor. However, in the case of
      tRNA(UGA)(Ser), TPsiC loop-D loop interaction was further required for
      recognition, suggesting that mt SerRS recognizes the two substrates by distinct
      mechanisms. mt SerRS could slightly but significantly misacylate mitochondrial
      tRNA(Gln), which has the same TPsiC loop sequence as tRNA(UGA)(Ser), implying
      that the fidelity of mitochondrial translation is maintained by kinetic
      discrimination of tRNAs in the network of aminoacyl-tRNA synthetases.

PMID- 11577084
TI  - The Stat1 binding motif of the interferon-gamma receptor is sufficient to mediate
      Stat5 activation and its repression by SOCS3.
AB  - Signal transduction via the interferon-gamma (IFN-gamma) receptor requires the
      tyrosine phosphorylation of signal transducers and activators of transcription
      (Stats). Whereas tyrosine phosphorylation of Stat1 occurs in all cells,
      activation of Stat5 by IFN-gamma is cell type-restricted. Here we investigated
      the mechanism of Stat5 activation by the IFN-gamma receptor. In transfection
      assays both Stat5 isoforms, Stat5a and Stat5b, were phosphorylated on tyrosine in
      response to IFN-gamma. Stat5 activation required the presence of tyrosine 420
      (Tyr-420) in the murine IFNGR1 receptor chain, which also serves as the Stat1
      binding site. Moreover, a peptide including Tyr-440, the Stat1 binding site of
      the human IFNGR1 chain, conferred the ability upon a synthetic receptor to
      activate Stat5. Suppressor of cytokine signaling 3 (SOCS3) inhibited the
      activation of Stat5 by the IFN-gamma receptor, and the Tyr-440-containing peptide
      stretch was sufficient for repression. SOCS3 expression had little effect on the
      activity of Jak kinases not associated with cytokine receptors. In IFN-gamma
      treated, Stat1-deficient fibroblasts Stat5 was inefficient in inducing
      transcription of a Stat-dependent reporter gene, suggesting it does not per se
      make a major contribution to the expression of IFN-gamma-responsive genes.

PMID- 11577085
TI  - Modulations of glypican-1 heparan sulfate structure by inhibition of endogenous
      polyamine synthesis. Mapping of spermine-binding sites and heparanase, heparin
      lyase, and nitric oxide/nitrite cleavage sites.
AB  - Cell surface heparan sulfate proteoglycans facilitate uptake of growth-promoting
      polyamines (Belting, M., Persson, S., and Fransson, L.-A. (1999) Biochem. J. 338,
      317-323; Belting, M., Borsig, L., Fuster, M. M., Brown, J. R., Persson, L.,
      Fransson, L.-A., and Esko, J. D. (2001) Proc. Natl. Acad. Sci. U. S. A., in
      press). Here, we have analyzed the effect of polyamine deprivation on the
      structure and polyamine affinity of the heparan sulfate chains in various
      glypican-1 glycoforms synthesized by a transformed cell line (ECV 304). Heparan
      sulfate chains of glypican-1 were either cleaved with heparanase at sites
      embracing the highly modified regions or with nitrite at N-unsubstituted
      glucosamine residues. The products were separated and further degraded by heparin
      lyase to identify sulfated iduronic acid. Polyamine affinity was assessed by
      chromatography on agarose substituted with the polyamine spermine. In heparan
      sulfate made by cells with undisturbed endogenous polyamine synthesis, free amino
      groups were restricted to the unmodified, unsulfated segments, especially near
      the core protein. Spermine high affinity binding sites were located to the
      modified and highly sulfated segments that were released by heparanase. In cells
      with up-regulated polyamine uptake, heparan sulfate contained an increased number
      of clustered N-unsubstituted glucosamines and sulfated iduronic acid residues.
      This resulted in a greater number of NO/nitrite-sensitive cleavage sites near the
      potential spermine-binding sites. Endogenous degradation by heparanase and NO
      derived nitrite in polyamine-deprived cells generated a separate pool of heparan
      sulfate oligosaccharides with an exceptionally high affinity for spermine.
      Spermine uptake in polyamine-deprived cells was reduced when NO/nitrite-generated
      degradation of heparan sulfate was inhibited. The results suggest a functional
      interplay between glypican recycling, NO/nitrite-generated heparan sulfate
      degradation, and polyamine uptake.

PMID- 11577086
TI  - Activation and mitochondrial translocation of protein kinase Cdelta are necessary
      for insulin stimulation of pyruvate dehydrogenase complex activity in muscle and
      liver cells.
AB  - In L6 skeletal muscle cells and immortalized hepatocytes, insulin induced a 2
      fold increase in the activity of the pyruvate dehydrogenase (PDH) complex. This
      effect was almost completely blocked by the protein kinase C (PKC) delta
      inhibitor Rottlerin and by PKCdelta antisense oligonucleotides. At variance,
      overexpression of wild-type PKCdelta or of an active PKCdelta mutant induced PDH
      complex activity in both L6 and liver cells. Insulin stimulation of the activity
      of the PDH complex was accompanied by a 2.5-fold increase in PDH phosphatases 1
      and 2 (PDP1/2) activity with no change in the activity of PDH kinase. PKCdelta
      antisense blocked insulin activation of PDP1/2, the same as with PDH. In insulin
      exposed cells, PDP1/2 activation was paralleled by activation and mitochondrial
      translocation of PKCdelta, as revealed by cell subfractionation and confocal
      microscopy studies. The mitochondrial translocation of PKCdelta, like its
      activation, was prevented by Rottlerin. In extracts from insulin-stimulated
      cells, PKCdelta co-precipitated with PDP1/2. PKCdelta also bound to PDP1/2 in
      overlay blots, suggesting that direct PKCdelta-PDP interaction may occur in vivo
      as well. In intact cells, insulin exposure determined PDP1/2 phosphorylation,
      which was specifically prevented by PKCdelta antisense. PKCdelta also
      phosphorylated PDP in vitro, followed by PDP1/2 activation. Thus, in muscle and
      liver cells, insulin causes activation and mitochondrial translocation of
      PKCdelta, accompanied by PDP phosphorylation and activation. These events are
      necessary for insulin activation of the PDH complex in these cells.

PMID- 11577087
TI  - p38 mitogen-activated protein kinase activates peroxisome proliferator-activated
      receptor alpha: a potential role in the cardiac metabolic stress response.
AB  - The expression of enzymes involved in fatty acid beta-oxidation (FAO), the
      principal source of energy production in the adult mammalian heart, is controlled
      at the transcriptional level via the nuclear receptor peroxisome proliferator
      activated receptor alpha (PPARalpha). Evidence has emerged that PPARalpha
      activity is activated as a component of an energy metabolic stress response. The
      p38 mitogen-activated protein kinase (MAPK) pathway is activated by cellular
      stressors in the heart, including ischemia, hypoxia, and hypertrophic growth
      stimuli. We show here that PPARalpha is phosphorylated in response to stress
      stimuli in rat neonatal cardiac myocytes; in vitro kinase assays demonstrated
      that p38 MAPK phosphorylates serine residues located within the NH(2)-terminal
      A/B domain of the protein. Transient transfection studies in cardiac myocytes and
      in CV-1 cells utilizing homologous and heterologous PPARalpha target element
      reporters and mammalian one-hybrid transcription assays revealed that p38 MAPK
      phosphorylation of PPARalpha significantly enhanced ligand-dependent
      transactivation. Cotransfection studies performed with several known coactivators
      of PPARalpha demonstrated that p38 MAPK markedly increased coactivation
      specifically by PGC-1, a transcriptional coactivator implicated in myocyte energy
      metabolic gene regulation and mitochondrial biogenesis. These results identify
      PPARalpha as a downstream effector of p38 kinase-dependent stress-activated
      signaling in the heart, linking extracellular stressors to alterations in energy
      metabolic gene expression.

PMID- 11577088
TI  - 14-3-3 proteins mediate an essential anti-apoptotic signal.
AB  - The 14-3-3 proteins are a family of highly conserved eukaryotic regulatory
      molecules that play important roles in many biological processes including cell
      cycle control and regulation of cell death. They are able to carry out these
      effects through binding and modulating the activity of a host of signaling
      proteins. The ability of 14-3-3 to inhibit Bad and other proapoptotic proteins
      argues that 14-3-3 can support cell survival. To examine this issue in a global
      sense, a specific inhibitor of 14-3-3/ligand interactions, difopein, was used.
      Difopein expression led to induction of apoptosis. Studies using various
      components of survival and death signaling pathways were consistent with a vital
      role for 14-3-3/ligand interactions in signal transduction from upstream pro
      survival kinases to the core apoptotic machinery. Because these kinases often
      become activated during oncogenesis, the effect of difopein on cell death induced
      by antineoplastic drugs was examined. It was found that difopein enhances the
      ability of cisplatin to kill cells. These data support the model that 14-3-3,
      through binding to Bad and other ligands, is critical for cell survival
      signaling. Inhibition of 14-3-3 may represent a useful therapeutic target for
      treatment of cancer and other diseases involving inappropriate cell survival.

PMID- 11577089
TI  - Binding of the beta2 adrenergic receptor to N-ethylmaleimide-sensitive factor
      regulates receptor recycling.
AB  - Following agonist stimulation, most G protein-coupled receptors become
      desensitized and are internalized, either to be degraded or recycled back to the
      cell surface. What determines the fate of a specific receptor type after it is
      internalized is poorly understood. Here we show that the rapidly recycling beta2
      adrenergic receptor (beta2AR) binds via a determinant including the last three
      amino acids in its carboxyl-terminal tail to the membrane fusion regulatory
      protein, N-ethylmaleimide-sensitive factor (NSF). This is documented by in vitro
      overlay assays and by cellular coimmunoprecipitations. Receptors bearing
      mutations in any of the last three residues fail to interact with NSF. After
      stimulation with the agonist isoproterenol, a green fluorescent protein fusion of
      NSF colocalizes with the wild type beta2AR but not with a tail-mutated beta2AR.
      The beta2AR-NSF interaction is required for efficient internalization of the
      receptors and for their recycling to the cell surface. Mutations in the beta2AR
      tail that ablate NSF binding reduce the efficiency of receptor internalization
      upon agonist stimulation. Upon subsequent treatment of cells with the antagonist
      propranolol, wild type receptors return to the cell surface, while tail-mutated
      receptors remain sequestered. Thus, the direct binding of the beta2AR to NSF
      demonstrates how, after internalization, the fate of a receptor is reliant on a
      specific interaction with a component of the cellular membrane-trafficking
      machinery.

PMID- 11577090
TI  - Oxidized low density lipoprotein exposure alters the transcriptional response of
      macrophages to inflammatory stimulus.
AB  - Macrophage-derived foam cells in atherosclerotic lesions are generally thought to
      play a major role in the pathology of the disease. Because macrophages play a
      central role in the inflammatory response, and the atherosclerotic lesion has
      features associated with chronic inflammatory settings, we investigated foam cell
      inflammatory potential. THP-1-derived macrophages were treated with oxidized low
      density lipoprotein (OxLDL) for 3 days to lipid load the macrophages and
      establish a foam cell-like phenotype. The cells were then activated by treatment
      with lipopolysaccharide (LPS), and RNA was harvested at 0, 1, and 6 h after LPS
      addition. RNA from treated and control cells was hybridized to microarrays
      containing approximately 16,000 human cDNAs. Genes that exhibited a 4-fold or
      greater increase or decrease at either 1 or 6 h after LPS treatment were counted
      as LPS-responsive genes. Employing these criteria, 127 LPS-responsive genes were
      identified. Prior treatment of THP-1 macrophages with OxLDL affected the
      expression of 57 of these 127 genes. Among these 57 genes was a group of
      chemokine, cytokine, and signal transduction genes with pronounced expression
      changes. OxLDL pretreatment resulted in a significant perturbation of LPS-induced
      NF kappa B activation. Furthermore, some of the OxLDL effects appear to be
      mediated by the nuclear receptors retinoid X receptor and peroxisomal
      proliferator-activated receptor gamma because pretreatment of THP-1 macrophages
      with ligands for these receptors, followed by LPS treatment, recapitulates the
      OxLDL plus LPS results for several of the most significantly modulated genes.

PMID- 11577091
TI  - Disabled-2 mediates c-Fos suppression and the cell growth regulatory activity of
      retinoic acid in embryonic carcinoma cells.
AB  - F9 embryonic stem cell-like teratocarcinoma cells are widely used to study early
      embryonic development and cell differentiation. The cells can be induced by
      retinoic acid to undergo endodermal differentiation. The retinoic acid-induced
      differentiation accompanies cell growth suppression, and thus, F9 cells are also
      often used as a model for analysis of retinoic acid biological activity. We have
      recently shown that MAPK activation and c-Fos expression are uncoupled in F9
      cells upon retinoic acid-induced endodermal differentiation. The expression of
      the candidate tumor suppressor Disabled-2 is induced and correlates with cell
      growth suppression in F9 cells. We were not able to establish stable Disabled-2
      expression by cDNA transfection in F9 cells without induction of spontaneous cell
      differentiation. Transient transfection of Dab2 by adenoviral vector nevertheless
      suppresses Elk-1 phosphorylation, c-Fos expression, and cell growth. In PA-1,
      another teratocarcinoma cell line of human origin that has no or very low levels
      of Disabled-2, retinoic acid fails to induce Disabled-2, correlating with a lack
      of growth suppression, although PA-1 is responsive to retinoic acid in
      morphological change. Transfection and expression of Disabled-2 in PA-1 cells
      mimic the effects of retinoic acid on growth suppression; the Disabled-2
      expressing cells reach a much lower saturation density, and serum-stimulated c
      Fos expression is greatly suppressed and disassociated from MAPK activation.
      Thus, Dab2 is one of the principal genes induced by retinoic acid involved in
      cell growth suppression, and expression of Dab2 alone is sufficient for
      uncoupling of MAPK activation and c-Fos expression. Resistance to retinoic acid
      regulation in PA-1 cells likely results from defects in retinoic acid up
      regulation of Dab2 expression.

PMID- 11577092
TI  - Cloning and biochemical analysis of the tetrahymena origin binding protein TIF1:
      competitive DNA binding in vitro and in vivo to critical rDNA replication
      determinants.
AB  - Cis-acting type I elements regulate the initiation of DNA replication,
      replication fork movement, and transcription of the Tetrahymena thermophila rDNA
      minichromosome and are required for cell cycle-controlled replication and
      developmentally programmed gene amplification. Previous studies identified three
      in vitro single-stranded type I element binding activities that were proposed to
      play distinct roles in replication control. Here we describe the cloning of one
      of these genes, TIF1, and we provide evidence for its association with type I
      elements in vivo. Furthermore, we show that TIF1 interacts (in vitro and in vivo)
      with pause site elements (PSE), which co-localize with replication initiation and
      fork arrest sites, and are shown to be essential. The in vivo accessibility of
      PSE and type I elements to potassium permanganate suggests that origin regions
      are frequently unwound in native chromatin. TIF1 contains sequence similarity to
      the Solanum tuberosum single strand-specific transcription factor, p24, and a
      related Arabidopsis protein. Antisense inhibition studies suggest that TIF1
      competes with other proteins for PSE and type I element binding. TIF1 displays a
      marked strand bias in vivo, discriminating between origin- and promoter-proximal
      type I elements. We propose that this bias selectively modulates the binding of a
      different subset of proteins to the respective regulatory elements.

PMID- 11577093
TI  - Genetic analysis of the DNA-dependent protein kinase reveals an inhibitory role
      of Ku in late S-G2 phase DNA double-strand break repair.
AB  - Two major complementary double-strand break (DSB) repair pathways exist in
      vertebrates, homologous recombination (HR), which involves Rad54, and non
      homologous end-joining, which requires the DNA-dependent protein kinase (DNA-PK).
      DNA-PK comprises a catalytic subunit (DNA-PKcs) and a DNA-binding Ku70 and Ku80
      heterodimer. To define the activities of individual DNA-PK components in DSB
      repair, we targeted the DNA-PKcs gene in chicken DT40 cells. DNA-PKcs deficiency
      caused a DSB repair defect that was, unexpectedly, suppressed by KU70 disruption.
      We have shown previously that genetic ablation of Ku70 confers RAD54-dependent
      radioresistance on S-G(2) phase cells, when sister chromatids are available for
      HR repair. To test whether direct interference by Ku70 with HR might explain the
      Ku70(-/-)/DNA-PKcs(-/-/-) radioresistance, we monitored HR activities directly in
      Ku- and DNA-PKcs-deficient cells. The frequency of intrachromosomal HR induced by
      the I-SceI restriction enzyme was increased in the absence of Ku but not of DNA
      PKcs. Significantly, abrogation of HR activity by targeting RAD54 in Ku70(-/-) or
      DNA-PKcs(-/-/-) cells caused extreme radiosensitivity, suggesting that the
      relative radioresistance seen with loss of Ku70 was because of HR-dependent
      repair pathways. Our findings suggest that Ku can interfere with HR-mediated DSB
      repair, perhaps competing with HR for DSB recognition.

PMID- 11577095
TI  - Acetylation of MyoD by p300 requires more than its histone acetyltransferase
      domain.
AB  - MyoD, an essential transcription factor involved in muscle cell terminal
      differentiation, is regulated by acetylation, as are a number of other
      transcription factors, but the histone acetyltransferase enzyme responsible for
      this acetylation is a matter of controversy. In particular, contradictory
      findings have been reported concerning the ability of CBP/p300 to acetylate MyoD
      in vitro. Here we provide an explanation for this discrepancy: although full
      length p300 does indeed acetylate MyoD, a fragment of p300 corresponding to its
      histone acetyltransferase domain does not. In addition to clearly demonstrating
      that p300 acetylates MyoD in vitro, these results underscore the necessity of
      using full-length histone acetyltransferase enzymes to draw valid conclusions
      from acetylation experiments.

PMID- 11577094
TI  - Cloning and characterization of two promoters for the human HSAL2 gene and their
      transcriptional repression by the Wilms tumor suppressor gene product.
AB  - HSAL2 is a member of a gene family that encodes a group of putative developmental
      transcription factors. The HSAL gene complex was originally identified on the
      basis of DNA sequence homology to a region-specific homeotic gene (SAL) in
      Drosophila. This study reveals a novel, functional 5' exon for HSAL2 and
      demonstrates that two distinct HSAL2 gene transcripts arise from two overlapping
      transcription units, resulting in proteins that differ by 25 amino acids. By
      utilizing functional luciferase reporter assays, two distinct promoters for
      HSAL2, P1 for the proximal promoter (upstream of exon 1) and P2 for the distal
      promoter (upstream of exon 1A), were identified. Evaluation of mRNA prevalence
      and tissue specificity, with particular focus on adult tissues, revealed that
      production of mRNA from P1 was selective and relatively rare. Production of mRNA
      from P2 was demonstrably higher and was expressed by a greater number of tissues.
      In contradistinction, HSAL2 expression directed by P2 was undetectable in some
      malignant populations as opposed to their normal human counterparts, suggesting a
      potential role as a tumor suppressor gene. Consensus-binding sites were
      identified for several transcriptional factors, with multiple sites for WT-1, and
      Hox-1.3 present within both the P1 and P2 regions. In transient transfection
      assays, transcription from both HSAL2 P1 and P2 was strikingly repressed by the
      WT-1 tumor suppressor protein. These findings suggest that an intracellular WT
      1/HSAL2 pathway may play a role in development and hematopoiesis.

PMID- 11577096
TI  - Inhibition of integrin-linked kinase/protein kinase B/Akt signaling: mechanism
      for ganglioside-induced apoptosis.
AB  - Ganglioside GT1b inhibits keratinocyte attachment to and migration on a
      fibronectin matrix by binding to alpha(5)beta(1) and preventing alpha(5)beta(1)
      interaction with fibronectin. The role of gangliosides in triggering keratinocyte
      apoptosis, however, is unknown. Addition of GT1b to keratinocyte-derived SCC12
      cells, grown in serum-free medium but exposed to fibronectin, suppressed Bad
      phosphorylation, activated caspase-9, and inhibited cyclin D and E expression,
      resulting in cell cycle arrest at G(1) phase and initiation of apoptosis. The
      mechanism of GT1b activation of caspase-9 involved inhibition of beta(1) integrin
      serine/threonine phosphorylation and decreased phosphorylation of both integrin
      linked kinase and protein kinase B/Akt at its Ser-473 site, leading to cytochrome
      c release from mitochondria. Consistently, blockade of GT1b function with anti
      GT1b antibody specifically activated the Ser-473 site of Akt, markedly
      suppressing apoptosis. The ganglioside-induced inhibition of Akt phosphorylation
      was GT1b-specific and was not observed when cells were treated with other
      keratinocyte gangliosides, including GD3. These studies suggest that the
      modulation of keratinocyte cell cycle and survival by GT1b is mediated by its
      direct interaction with alpha(5)beta(1) and resultant inhibition of the
      integrin/integrin-linked kinase/protein kinase B/Akt signaling pathway.

PMID- 11577097
TI  - Quantitative analysis of the effect of phosphoinositide interactions on the
      function of Dbl family proteins.
AB  - Normally, Rho GTPases are activated by the removal of bound GDP and the
      concomitant loading of GTP catalyzed by members of the Dbl family of guanine
      nucleotide exchange factors (GEFs). This family of GEFs invariantly contain a Dbl
      homology (DH) domain adjacent to a pleckstrin homology (PH) domain, and while the
      DH domain usually is sufficient to catalyze nucleotide exchange, possible roles
      for the conserved PH domain remain ambiguous. Here we demonstrate that the
      conserved PH domains of three distinct Dbl family proteins, intersectin, Dbs, and
      Tiam1, selectively bind lipid vesicles only when phosphoinositides are present.
      While the PH domains of intersectin and Dbs promiscuously bind several
      multiphosphorylated phosphoinositides, Tiam1 selectively interacts with
      phosphatidylinositol 3-phosphate (K(D) approximately 5-10 microm). In addition,
      and in contrast to recent reports, catalysis of nucleotide exchange on
      nonprenylated Rac1 provided by various extended portions of Tiam1 is not
      influenced by (a) soluble phosphoinositide head groups, (b) dibutyl versions of
      phosphoinositides, or (c) lipid vesicles containing phosphoinositides. Likewise,
      GEF activity afforded by DH/PH fragments of intersectin and Dbs are also not
      altered by phosphoinositide interactions. These results strongly suggest that
      unless all relevant components are localized to a lipid membrane surface, Dbl
      family GEFs generally are not intrinsically modulated by binding
      phosphoinositides.

PMID- 11577098
TI  - Solution structure of bacteriophage PRD1 vertex complex.
AB  - Bacteriophage PRD1 is a prototype of viruses with an internal membrane. The
      icosahedral capsid and major coat protein share structural similarity with the
      corresponding structures of adenovirus. The present study further explores
      similarities between these viruses, considering the 5-fold vertex assemblies. The
      vertex structure of bacteriophage PRD1 consists of proteins P2, P5, and P31. The
      vertex complex mediates host cell binding and controls double-stranded DNA
      delivery. Quaternary structures and interactions of purified spike proteins were
      studied by synchrotron radiation x-ray solution scattering. Low resolution models
      of the vertex proteins P5, P2, and P31 were reconstructed ab initio from the
      scattering data. Protein P5 is a long trimer that resembles the adenovirus spike
      protein pIV. The receptor-binding protein P2 is a 15.5-nm long, thin monomer and
      does not have an adenovirus counterpart. P31 forms a pentameric base with a
      maximum diameter of 8.5 nm, which is thinner than the adenovirus penton pIII. P5
      further polymerize into a nonameric form ((P5(3))(3)). In the presence of P31, P5
      associates into a P5(6):P31 complex. The constructed models of these assemblies
      provided support for a model of vertex assembly onto the virion. Although similar
      in overall architecture, clear differences between PRD1 and adenovirus spike
      assemblies have been revealed.

PMID- 11577099
TI  - Apolipoprotein A-V: a novel apolipoprotein associated with an early phase of
      liver regeneration.
AB  - Liver regeneration in response to various forms of liver injury is a complex
      process, which ultimately results in restoration of the original liver mass and
      function. Because the underlying mechanisms that initiate this response are still
      incompletely defined, this study was aimed to identify novel factors. Liver genes
      that were up-regulated 6 h after 70% hepatectomy (PHx) in the rat were selected
      by cDNA subtractive hybridization. Besides known genes associated with cell
      proliferation, several novel genes were isolated. The novel gene that was most up
      regulated was further studied. Its mRNA showed a liver-specific expression and
      encoded a protein comprising 367 amino acids. The mouse and human cDNA analogues
      were also isolated and appeared to be highly homologous. The human gene analogue
      was located at an apolipoprotein gene cluster on chromosome 11q23. The protein
      encoded by this gene had appreciable homology with apolipoproteins A-I and A-IV.
      Maximal expression of the gene in the rat liver and its gene product in rat
      plasma was observed 6 h after PHx. The protein was present in plasma fractions
      containing high density lipoprotein particles. Therefore, we have identified a
      novel apolipoprotein, designated apolipoprotein A-V, that is associated with an
      early phase of liver regeneration.

PMID- 11577100
TI  - Transfer of sulfur from IscS to IscU during Fe/S cluster assembly.
AB  - The cysteine desulfurase enzymes NifS and IscS provide sulfur for the
      biosynthesis of Fe/S proteins. NifU and IscU have been proposed to serve as
      template or scaffold proteins in the initial Fe/S cluster assembly events, but
      the mechanism of sulfur transfer from NifS or IscS to NifU or IscU has not been
      elucidated. We have employed [(35)S]cysteine radiotracer studies to monitor
      sulfur transfer between IscS and IscU from Escherichia coli and have used direct
      binding measurements to investigate interactions between the proteins. IscS
      catalyzed transfer of (35)S from [(35)S]cysteine to IscU in the absence of
      additional thiol reagents, suggesting that transfer can occur directly and
      without involvement of an intermediate carrier. Surface plasmon resonance studies
      and isothermal titration calorimetry measurements further revealed that IscU
      binds to IscS with high affinity (K(d) approximately 2 microm) in support of a
      direct transfer mechanism. Transfer was inhibited by treatment of IscU with
      iodoacetamide, and (35)S was released by reducing reagents, suggesting that
      transfer of persulfide sulfur occurs to cysteinyl groups of IscU. A deletion
      mutant of IscS lacking C-terminal residues 376-413 (IscSDelta376-413) displayed
      cysteine desulfurase activity similar to the full-length protein but exhibited
      lower binding affinity for IscU, decreased ability to transfer (35)S to IscU, and
      reduced activity in assays of Fe/S cluster assembly on IscU. The findings with
      IscSDelta376-413 provide additional support for a mechanism of sulfur transfer
      involving a direct interaction between IscS and IscU and suggest that the C
      terminal region of IscS may be important for binding IscU.

PMID- 11577101
TI  - Deletion of the RNA polymerase subunit RPB4 acts as a global, not stress
      specific, shut-off switch for RNA polymerase II transcription at high
      temperatures.
AB  - We used whole genome expression analysis to investigate the changes in the mRNA
      profile in cells lacking the Saccharomyces cerevisiae RNA polymerase II subunit
      RPB4 (Delta RPB4). Our results indicated that an essentially complete shutdown of
      transcription occurs upon temperature shift of this conditionally lethal mutant;
      98% of mRNA transcript levels decrease at least 2-fold, 96% at least 4-fold. This
      data was supported by in vivo experiments that revealed a rapid and greater than
      5-fold decline in steady state poly(A) RNA levels after the temperature shift.
      Expression of several individual genes, measured by Northern analysis, was also
      consistent with the whole genome expression profile. Finally we demonstrated that
      the loss of RNA polymerase II activity causes secondary effects on RNA polymerase
      I, but not RNA polymerase III, transcription. The transcription phenotype of the
      Delta RPB4 mutant closely mirrors that of the temperature-sensitive rpb1-1 mutant
      frequently implemented as a tool to inactivate the RNA polymerase II in vivo.
      Therefore, the Delta RPB4 mutant can be used to easily design strains that enable
      the study of distinct post-transcriptional cellular processes in the absence of
      RNA polymerase II transcription.

PMID- 11577102
TI  - Functional modulation of the glucocorticoid receptor and suppression of NF-kappaB
      dependent transcription by ursodeoxycholic acid.
AB  - Ursodeoxycholic acid (UDCA) is the current mainstay of treatment for various
      liver diseases including primary biliary cirrhosis. UDCA acts as a bile
      secretagogue, cytoprotective agent, immunomodulator, and inhibitor of cellular
      apoptosis. Despite this cumulative evidence of the cytoprotective and
      immunosuppressive effects of UDCA, both the target molecule and pathway of UDCA
      action remain unknown. We previously described that, in the absence of
      glucocorticoid ligand, UDCA activates the glucocorticoid receptor (GR) into DNA
      binding species but does not elicit its transactivational function in a transient
      transfection assay. Here we further studied the molecular mechanism of UDCA
      action and revealed that the ligand binding domain of the GR is responsible for
      UDCA-dependent nuclear translocation of the GR. Indeed, we demonstrated that UDCA
      acts on the distinct region of the ligand binding domain when compared with the
      classical GR agonist dexamethasone, resulting in loss of coactivator recruitment
      and differential regulation of gene expression by the GR. Our data clearly
      indicated that UDCA, at least in part via activation of the GR, suppresses NF
      kappaB-dependent transcription through the intervention of GR-p65 interaction.
      Together with the established clinical safety of UDCA, we may propose that UDCA
      could be a prototypical compound for development of a novel and selective GR
      modifier.

PMID- 11577103
TI  - c-Jun potentiates the functional interaction between the amino and carboxyl
      termini of the androgen receptor.
AB  - The transactivation functions of the human androgen receptor (hAR) are regulated
      by several accessory factors that can be either positive or negative. One factor
      that has been previously shown to mediate hAR transactivation is the proto
      oncoprotein c-Jun. The positive effect is a primary one, can be exerted by both
      endogenous and exogenous c-Jun, and requires multiple regions of c-Jun. However,
      the exact mechanism by which c-Jun exerts its enhancing function is unknown. In
      this study, we have used a mammalian two-hybrid system to ask if c-Jun influences
      the ligand-dependent amino- to carboxyl-terminal (N-to-C) interaction of hAR,
      which is thought to be responsible for the homodimerization of this receptor. Our
      results show that c-Jun enhances both hAR N-to-C terminal interaction and DNA
      binding in vitro. We have also tested a panel of c-Jun and c-Fos mutants for
      their activities on the N-to-C interaction, and the data demonstrate that the
      activities of these mutants parallel their activities on hAR transactivation. A
      mutation in the hAR activation function-2 (AF-2) abrogates N-to-C interaction,
      DNA binding, and transactivation, and these activities are not rescued by
      exogenous c-Jun. Interestingly, the p160 coactivator TIF2 can stimulate hAR N-to
      C interaction, a finding consistent with the effect on hAR transactivation. These
      data strongly suggest that the hAR N-to-C interaction is the target of c-Jun
      action, and this activity requires a functional receptor AF-2.

PMID- 11577104
TI  - Phosphatidylinositol 3,4,5-trisphosphate directs association of Src homology 2
      containing signaling proteins with gelsolin.
AB  - Podosomes are adhesion structures in osteoclasts and are structurally related to
      focal adhesions mediating cell motility during bone resorption. Here we show that
      gelsolin coprecipitates some of the focal adhesion-associated proteins such as c
      Src, phosphoinositide 3-kinase (PI3K), p130(Cas), focal adhesion kinase, integrin
      alpha(v)beta(3), vinculin, talin, and paxillin. These proteins were inducibly
      tyrosine-phosphorylated in response to integrin activation by osteopontin.
      Previous studies have defined unique biochemical properties of gelsolin related
      to phosphatidylinositol 3,4,5-trisphosphate in osteoclast podosomes, and here we
      demonstrate phosphatidylinositol 3,4,5-trisphosphate/gelsolin function in
      mediating organization of the podosome signaling complex. Overlay and GST pull
      down assays demonstrated strong phosphatidylinositol 3,4,5-trisphosphate-PI3K
      interactions based on the Src homology 2 domains of PI3K. Furthermore, lipid
      extraction of lysates from activated osteoclasts eliminated interaction between
      gelsolin, c-Src, PI3K, and focal adhesion kinase despite equal amounts of
      gelsolin in both the lipid-extracted and unextracted experiment. The cytoplasmic
      protein tyrosine phosphatase (PTP)-proline-glutamic acid-serine-threonine amino
      acid sequences (PEST) was also found to be associated with gelsolin in osteoclast
      podosomes and with stimulation of alpha(v)beta(3)-regulated phosphorylation of
      PTP-PEST. We conclude that gelsolin plays a key role in recruitment of signaling
      proteins to the plasma membrane through phospholipid-protein interactions and by
      regulation of their phosphorylation status through its association with PTP-PEST.
      Because both gelsolin deficiency and PI3K inhibition impair bone resorption, we
      conclude that phosphatidylinositol 3,4,5-trisphosphate-based protein interactions
      are critical for osteoclast function.

PMID- 11577105
TI  - Involvement of the flavin si-face tyrosine on the structure and function of
      ferredoxin-NADP+ reductases.
AB  - In ferredoxin-NADP(+) reductase (FNR), FAD is bound outside of an anti-parallel
      beta-barrel with the isoalloxazine lying in a two-tyrosine pocket. To elucidate
      the function of the flavin si-face tyrosine (Tyr-89 in pea FNR) on the enzyme
      structure and catalysis, we performed ab initio molecular orbital calculations
      and site-directed mutagenesis. Our results indicate that the position of Tyr-89
      in pea FNR is mainly governed by the energetic minimum of the pairwise
      interaction between the phenol ring and the flavin. Moreover, most of FNR-like
      proteins displayed geometries for the si-face tyrosine phenol and the flavin,
      which correspond to the more negative free energy theoretical value. FNR mutants
      were obtained replacing Tyr-89 by Phe, Trp, Ser, or Gly. Structural and
      functional features of purified FNR mutants indicate that aromaticity on residue
      89 is essential for FAD binding and proper folding of the protein. Moreover,
      hydrogen bonding through the Tyr-89 hydroxyl group may be responsible of the
      correct positioning of FAD and the substrate NADP(+)

PMID- 11577106
TI  - Folding pathway mediated by an intramolecular chaperone: propeptide release
      modulates activation precision of pro-subtilisin.
AB  - Propeptides of several proteases directly catalyze the protein folding reaction.
      Uncatalyzed folding traps these proteases into inactive molten-globule-like
      conformers that switch into active enzymes only when their cognate propeptides
      are added in trans. Although tight binding and proteolytic susceptibility forces
      propeptides to function as single turnover catalysts, the significance of their
      inhibitory function and the mechanism of activation remain unclear. Using pro
      subtilisin as a model, we establish that precursor activation is a highly
      coordinated process that involves synchronized folding, autoprocessing,
      propeptide release, and protease activation. Our results demonstrate that
      activation is controlled by release of the first free active protease molecule.
      This triggers an exponential cascade that selectively targets the inhibitory
      propeptide in the autoprocessed complex as its substrate. However, a mutant
      precursor that enhances propeptide release can drastically reduce the folding
      efficiency by altering the synergy between individual stages. Our results
      represent the first demonstration that propeptide release, not precursor folding,
      is the rate-determining step and provides the basis for the proposed model for
      precise spatial and temporal activation that allows proteases to function as
      regulators of biological function.

PMID- 11577107
TI  - Crystal structure at 1.5-A resolution of Pyrus pyrifolia pistil ribonuclease
      responsible for gametophytic self-incompatibility.
AB  - The crystal structure of the Pyrus pyrifolia pistil ribonuclease (S(3)-RNase)
      responsible for gametophytic self-incompatibility was determined at 1.5-A
      resolution. It consists of eight helices and seven beta-strands, and its folding
      topology is typical of RNase T(2) family enzymes. Based on a structural
      comparison of S(3)-RNase with RNase Rh, a fungal RNase T(2) family enzyme, the
      active site residues of S(3)-RNase assigned were His(33) and His(88) as catalysts
      and Glu(84) and Lys(87) as stabilizers of an intermediate in the transition
      state. Moreover, amino acid residues that constitute substrate binding sites of
      the two RNases could be superimposed geometrically. A hypervariable (HV) region
      that has an S-allele-specific sequence comprises a long loop and short alpha
      helix. This region is far from the active site cleft, exposed on the molecule's
      surface, and positively charged. Four positively selected (PS) regions, in which
      the number of nonsynonymous substitutions exceeds that of synonymous ones, are
      located on either side of the active site cleft, and accessible to solvent. These
      structural features suggest that the HV or PS regions may interact with a pollen
      S-gene product(s) to recognize self and non-self pollen.

PMID- 11577108
TI  - Hyperthermophilic topoisomerase I from Thermotoga maritima. A very efficient
      enzyme that functions independently of zinc binding.
AB  - Topoisomerases, by controlling DNA supercoiling state, are key enzymes for
      adaptation to high temperatures in thermophilic organisms. We focus here on the
      topoisomerase I from the hyperthermophilic bacterium Thermotoga maritima (optimal
      growth temperature, 80 degrees C). To determine the properties of the enzyme
      compared with those of its mesophilic homologs, we overexpressed T. maritima
      topoisomerase I in Escherichia coli and purified it to near homogeneity. We show
      that T. maritima topoisomerase I exhibits a very high DNA relaxing activity.
      Mapping of the cleavage sites on a variety of single-stranded oligonucleotides
      indicates a strong preference for a cytosine at position -4 of the cleavage, a
      property shared by E. coli topoisomerase I and archaeal reverse gyrases. As
      expected, the mutation of the putative active site Tyr 288 to Phe led to a
      totally inactive protein. To investigate the role of the unique zinc motif (Cys-X
      Cys-X(16)-Cys-X-Cys) present in T. maritima topoisomerase I, experiments have
      been performed with the protein mutated on the tetracysteine motif. Strikingly,
      the results show that zinc binding is not required for DNA relaxation activity,
      contrary to the E. coli enzyme. Furthermore, neither thermostability nor cleavage
      specificity is altered in this mutant. This finding opens the question of the
      role of the zinc-binding motif in T. maritima topoisomerase I and suggests that
      this hyperthermophilic topoisomerase possesses a different mechanism from its
      mesophilic homolog.

PMID- 11577109
TI  - Sheep prion protein synthetic peptide spanning helix 1 and beta-strand 2
      (residues 142-166) shows beta-hairpin structure in solution.
AB  - According to the "protein only" hypothesis, a conformational conversion of the
      non-pathogenic "cellular" prion isoform into a pathogenic "scrapie" isoform is
      the fundamental event in the onset of prion diseases. During this pathogenic
      conversion, helix H1 and two adjacent surface loops L2 and L3 of the normal prion
      protein are thought to undergo a conformational transition into an extended beta
      like structure, which is prompted by interactions with the pre-existing beta
      sheet. To get more insight into the interaction between the helix and one of the
      beta-strands in the partially unfolded prion protein, the solution structure of a
      synthetic linear peptide spanning helix H1 and beta-strand S2 (residues 142-166
      in human numbering) was studied by circular dichroism and nuclear magnetic
      resonance spectroscopies. We found that, in contrast to many prion fragments
      studied earlier, this peptide (i) is highly soluble and does not aggregate up to
      a millimolar concentration range in aqueous medium and (ii) exhibits an intrinsic
      propensity to a beta-hairpin like conformation at neutral pH. This beta
      propensity can be one of the internal driving forces of the molecular
      rearrangement responsible for the pathogenic conversion of the prion protein.

PMID- 11577110
TI  - Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role for
      endocytic accessory proteins.
AB  - Clathrin-mediated endocytosis is a major pathway for the internalization of
      macromolecules into the cytoplasm of eukaryotic cells. The principle coat
      components, clathrin and the AP-2 adaptor complex, assemble a polyhedral lattice
      at plasma membrane bud sites with the aid of several endocytic accessory
      proteins. Here, we show that huntingtin-interacting protein 1 (HIP1), a binding
      partner of huntingtin, copurifies with brain clathrin-coated vesicles and
      associates directly with both AP-2 and clathrin. The discrete interaction
      sequences within HIP1 that facilitate binding are analogous to motifs present in
      other accessory proteins, including AP180, amphiphysin, and epsin. Bound to a
      phosphoinositide-containing membrane surface via an epsin N-terminal homology
      (ENTH) domain, HIP1 associates with AP-2 to provide coincident clathrin-binding
      sites that together efficiently recruit clathrin to the bilayer. Our data
      implicate HIP1 in endocytosis, and the similar modular architecture and function
      of HIP1, epsin, and AP180 suggest a common role in lipid-regulated clathrin
      lattice biogenesis.

PMID- 11577111
TI  - Characteristics and structural requirements of apical sorting of the rat growth
      hormone through the O-glycosylated stalk region of intestinal sucrase-isomaltase.
AB  - The apical sorting of the small intestinal membrane glycoprotein sucrase
      isomaltase (SI) depends on the presence of O-linked glycans and the transmembrane
      domain. Here, we investigate the role of O-glycans carried by the Ser/Thr-rich
      stalk region of SI as an apical sorting signal and evaluate the spatial
      requirements for an efficient recognition of this signal. Several hybrid proteins
      are generated comprising the unsorted and unglycosylated protein, the rat growth
      hormone (rGH), fused to either the transmembrane domain of SI (GH-SI(TM)), or the
      transmembrane and the stalk domains (GH-SI(SR/TM)). Both constructs are randomly
      distributed over the apical and basolateral membranes of MDCK cells indicating
      that neither the transmembrane domain nor the O-glycans are sufficient per se for
      an apical delivery. Only when a polyglycine spacer is inserted between the stalk
      region of SI and the luminal part of rGH in the GH-SI(Gly/SR/TM) fusion protein
      does efficient apical sorting of an O-glycosylated protein as well as a time
      dependent association with detergent-insoluble lipid microdomains occur.
      Obviously, the polyglycine spacer facilitates the accessibility of the O-glycans
      in GH-SI(Gly/SR/TM) to a putative sorting receptor, whereas these glycans are
      inadequately recognized in GH-SI(SR/TM). We conclude that the O-glycans in the
      stalk region of SI act as an apical sorting signal within a sorting machinery
      that comprises at least a carbohydrate-binding protein and fulfills specific
      spatial requirements provided, for example by a polyglycine spacer in the context
      of rGH or the P-domain within the SI enzyme complex.

PMID- 11577112
TI  - The hypocholesterolemic agent LY295427 reverses suppression of sterol regulatory
      element-binding protein processing mediated by oxysterols.
AB  - The sterol LY295427 reduces plasma cholesterol levels in animals by increasing
      the expression of hepatic low density lipoprotein (LDL) receptors. Here we trace
      the hypocholesterolemic activity of LY295427 to an ability to reverse oxysterol
      mediated suppression of sterol regulatory element-binding protein (SREBP)
      processing. Micromolar concentrations of LY295427 induced the metabolism of LDL
      in oxysterol-treated cultured cells and inhibited the stimulation of cholesteryl
      ester synthesis mediated by oxysterols. cDNA microarray and RNA blotting
      experiments revealed that LY295427 increased levels of the LDL receptor mRNA and
      those of other SREBP target genes. The compound stimulated the accumulation of
      SREBPs in the nuclei of cells grown in the presence of oxysterols within 4-6 h of
      addition to the medium. Induction required components of the normal SREBP
      processing pathway, including the SREBP cleavage-activating protein and the Site
      1 protease. LY295427 overcame the suppression of SREBP processing mediated by
      several oxysterols but not by LDL-derived cholesterol. We conclude that LY295427
      achieves a therapeutically desirable end point by an unique mechanism of action.

PMID- 11577113
TI  - Cloning, sequencing, heterologous expression, purification, and characterization
      of adenosylcobalamin-dependent D-ornithine aminomutase from Clostridium
      sticklandii.
AB  - D-Ornithine aminomutase from Clostridium sticklandii catalyzes the reversible
      rearrangement of d-ornithine to (2R,4S)-2,4-diaminopentanoic acid. The two genes
      encoding d-ornithine aminomutase have been cloned, sequenced, and expressed in
      Escherichia coli. The oraS gene, which encodes a protein of 121 amino acid
      residues with M(r) 12,800, is situated upstream of the oraE gene, which encodes a
      protein of 753 amino acid residues with M(r) 82,900. The holoenzyme appears to
      comprise a alpha(2)beta(2)-heterotetramer. OraS shows no significant homology to
      other proteins in the Swiss-Prot data base. The deduced amino acid sequence of
      OraE includes a conserved base-off/histidine-on cobalamin-binding motif, DXHXXG.
      OraE was expressed in E. coli as inclusion bodies. Refolding experiments on OraE
      indicate that the interactions between OraS and OraE and the binding of either
      pyridoxal phosphate or adenosylcobalamin play important roles in refolding
      process. The K(m) values for d-ornithine, 5'-deoxyadenosylcobalamin (AdoCbl), and
      pyridoxal 5'-phosphate (PLP) are 44.5 +/- 2.8, 0.43 +/- 0.04, and 1.5 +/- 0.1
      microm, respectively; the k(cat) is 6.3 +/- 0.1 s(-1). The reaction was
      absolutely dependent upon OraE, OraS, AdoCbl, PLP, and D-ornithine being present
      in the assay; no other cofactors were required. A red-shift in UV-visible
      absorption spectrum is observed when free adenosylcobinamide is bound by
      recombinant D-ornithine aminomutase and no significant change in spectrum when
      free adenosylcobinamide is bound by mutant OraE-H618G, demonstrating that the
      enzyme binds adenosylcobalamin in base-off/histidine-on mode.

PMID- 11577114
TI  - CAD/DFF40 nuclease is dispensable for high molecular weight DNA cleavage and
      stage I chromatin condensation in apoptosis.
AB  - DNA degradation during apoptotic execution generally occurs at two levels: early
      as high molecular weight (HMW) fragments and later on as oligonucleosomal
      fragments. Two nucleases, CAD/CPAN/DFF40 and endonuclease G, can digest nuclear
      chromatin to produce the oligonucleosomal fragments, and it has been suggested
      that CAD might be responsible for HMW DNA cleavage. To more clearly define the
      role of CAD in nuclear disassembly, we have generated CAD(-/-) sublines of
      chicken DT40 cells in which the entire CAD open reading frame has been deleted.
      These cells grow normally and undergo apoptosis with kinetics essentially
      identical to wild type cells. However, they fail to undergo detectable
      oligonucleosomal fragmentation, proving that CAD is essential for this stage of
      DNA cleavage, at least in DT40 cells. Other aspects of nuclear disassembly,
      including HMW DNA cleavage and early stage apoptotic chromatin condensation
      against the nuclear periphery proceed normally in the absence of CAD. However,
      the final stages of chromatin condensation and nuclear fragmentation do not
      occur. Our results demonstrate that CAD is required for complete disassembly of
      the nucleus during apoptosis and reveal the existence of one or more as yet
      unidentified second factors responsible for HMW DNA cleavage and the early stages
      of apoptotic chromatin condensation.

PMID- 11577115
TI  - Fast hydride transfer in proton-translocating transhydrogenase revealed in a
      rapid mixing continuous flow device.
AB  - Transhydrogenase couples the redox reaction between NAD(H) and NADP(H) to proton
      translocation across a membrane. Coupling is achieved through changes in protein
      conformation. Upon mixing, the isolated nucleotide-binding components of
      transhydrogenase (dI, which binds NAD(H), and dIII, which binds NADP(H)) form a
      catalytic dI(2).dIII(1) complex, the structure of which was recently solved by x
      ray crystallography. The fluorescence from an engineered Trp in dIII changes when
      bound NADP(+) is reduced. Using a continuous flow device, we have measured the
      Trp fluorescence change when dI(2).dIII(1) complexes catalyze reduction of
      NADP(+) by NADH on a sub-millisecond scale. At elevated NADH concentrations, the
      first-order rate constant of the reaction approaches 21,200 s(-1), which is
      larger than that measured for redox reactions of nicotinamide nucleotides in
      other, soluble enzymes. Rather high concentrations of NADH are required to
      saturate the reaction. The deuterium isotope effect is small. Comparison with the
      rate of the reverse reaction (oxidation of NADPH by NAD(+)) reveals that the
      equilibrium constant for the redox reaction on the complex is >36. This high
      value might be important in ensuring high turnover rates in the intact enzyme.

PMID- 11577116
TI  - Yeast Ull1/Siz1 is a novel SUMO1/Smt3 ligase for septin components and functions
      as an adaptor between conjugating enzyme and substrates.
AB  - SUMO1/Smt3, a ubiquitin-like protein modifier, is known to conjugate to other
      proteins and modulate their functions in various important processes. Similar to
      the ubiquitin conjugation system, SUMO/Smt3 is transferred to substrate lysine
      residues through the thioester cascade of E1 (activating enzyme) and E2
      (conjugating enzyme). In our previous report (Takahashi, Y., Toh-e, A., and
      Kikuchi, Y. (2001) Gene 275, 223-231), we showed that Siz1/Ull1 (YDR409w) of
      budding yeast, a member of the human PIAS family containing a RING-like domain,
      is a strong candidate for SUMO1/Smt3 ligase because the SUMO1/Smt3 modification
      of septin components was abolished in the ull1 mutant and Ull1 associated with E2
      (Ubc9) and the substrates (septin components) in immunoprecipitation experiments.
      Here we have developed an in vitro Smt3 conjugation system for a septin component
      (Cdc3) using purified recombinant proteins. In this system, Ull1 is additionally
      required as well as E1 (Sua1.Uba2 complex), E2 (Ubc9), and ATP. A cysteine
      residue of the RING-like domain was essential for the conjugation both in vivo
      and in vitro. Furthermore, a region containing the RING-like domain directly
      interacted with Ubc9 and Cdc3. Thus, this SUMO/Smt3 ligase functions as an
      adaptor between E2 and the target proteins.

PMID- 11577117
TI  - Bone marrow trephine biopsy.
AB  - Trephine biopsies of the bone marrow should be carried out, when clinically
      indicated, by trained individuals following a standard operating procedure. A
      bone marrow aspiration should be performed as part of the same procedure. For
      patient safety and convenience, biopsies are usually performed on the posterior
      iliac crest. The biopsy specimen should measure at least 1.6 cm and, if it does
      not, consideration should be given to repeating the procedure, possibly on the
      contralateral iliac crest. If bone marrow aspiration is found to be impossible,
      imprints from the biopsy specimen should be obtained. Otherwise, the specimen is
      placed immediately into fixative and after fixation is embedded in a resin or,
      more usually, decalcified and embedded in paraffin wax. Thin sections are cut and
      are stained, as a minimum, with haematoxylin and eosin and with a reticulin
      stain. A Giemsa stain is also desirable. A Perls' stain does not often give
      useful information and is not essential in every patient. The need for other
      histochemical or immunohistochemical stains is determined by the clinical
      circumstances and the preliminary findings. Trephine biopsy sections should be
      examined and reported in a systematic manner, assessment being made of the bones,
      the vessels and stroma, and the haemopoietic and any lymphoid or other tissue.
      Assessment should begin with a very low power objective, the entire section being
      examined. Further examination is then done with an intermediate and high power
      objective. Ideally, reporting of trephine biopsy sections should be done by an
      individual who is competent in both histopathology and haematology, and who is
      able to make an appropriate assessment of both the bone marrow aspirate and the
      trephine biopsy sections. When this is not possible, there should be close
      consultation between a haematologist and a histopathologist. The report should
      both describe the histological findings and give an interpretation of their
      importance. A signed or computer authorised report should be issued in a timely
      manner. If the report is a preliminary, this must be clearly stated.

PMID- 11577118
TI  - Vaccination to prevent varicella and shingles.
AB  - Vaccination of healthy children against varicella using the live attenuated Oka
      vaccine has been available in Japan and south Korea for several years. In 1996, a
      programme of universal vaccination of children to prevent varicella was
      introduced in the USA and other countries, including Canada, Germany, and Sweden,
      have licensed the vaccine for use in healthy children. This article reviews the
      origin of the Oka vaccine and the evidence for vaccine safety and efficacy in
      children and adults. Universal vaccination of children and targeted vaccination
      of groups at risk of severe varicella are discussed. The possible use of the Oka
      vaccine to prevent zoster is reviewed, and initiatives to develop new varicella
      zoster virus vaccines are outlined.

PMID- 11577119
TI  - Evidence for antibiotic induced Clostridium perfringens diarrhoea.
AB  - Clostridium difficile is a well documented cause of antibiotic associated
      diarrhoea in hospitalised patients, but may account for only approximately 20% of
      all cases. This leader reviews the current knowledge and understanding of the
      pathogenesis, epidemiology, and diagnosis of non-food borne Clostridium
      perfringens diarrhoea. Although enterotoxigenic C perfringens has been implicated
      in some C difficile negative cases of antibiotic associated diarrhoea, C
      perfringens enterotoxin detection methods are not part of the routine laboratory
      investigation of such cases. Testing for C perfringens enterotoxin in faecal
      samples from patients with antibiotic associated diarrhoea and sporadic diarrhoea
      on a routine basis would have considerable resource implications. Therefore,
      criteria for initiating investigations and optimum laboratory tests need to be
      established. In addition, establishing the true burden of C perfringens
      antibiotic associated diarrhoea is important before optimum control and treatment
      measures can be defined.

PMID- 11577120
TI  - An experimental inter-expert telepathology network using static imaging.
AB  - AIMS: To set up a network for remote consultation using static imaging
      telepathology via Internet connection between pathologists in different European
      countries, and to collect some numerical and subjective impressions on the
      usefulness of this form of telepathology. METHODS: A static image remote
      consultation network between 11 pathologists in nine European countries was set
      up; all pathologists were equipped with the same telepathology system. The
      pathologists formed three subject oriented subgroups concerned with prostate,
      melanoma, and soft tissue sarcoma pathology. Each pathologist sent and received a
      small number of cases, and data on each case were collected and analysed. The
      whole experiment was controlled through a World Wide Web site. RESULTS: A total
      of 56 case consultations on 34 different cases were exchanged. The average case
      document contained seven images, and contained 1.97 Mbytes of data. For cases in
      which data were recorded, average case preparation and remote consultation time
      was 55 minutes and 9.2 minutes, respectively. Transmission times averaged 3.9
      minutes. In subjective impressions, reservations were expressed in several cases
      regarding the confidence that could be given to the diagnosis from the images
      presented. CONCLUSIONS: Remote consultation by telepathology via the Internet is
      now technically feasible and reasonably user friendly, but is only suitable as a
      method of disease diagnosis in some cases.

PMID- 11577121
TI  - An audit of pathology lymph node dissection techniques in pylorus preserving
      Kausch-Whipple pancreatoduodenectomy specimens.
AB  - AIMS: To determine whether or not identifying recognised anatomical groupings of
      lymph nodes (LNs) improves LN yield in pancreatoduodenectomy resection specimens.
      METHODS: All the pathology reports from pancreatoduodenectomy resection specimens
      between January 1997 and September 1999, for one specialist pathologist at the
      Royal Liverpool University Hospital, were examined retrospectively. The total
      number of LNs found in each specimen was determined and the method of identifying
      LNs established for each case. LNs were found using either (1) the UICC TNM
      anatomical groupings, termed "grouped"; (2) the Japanese Pancreatic Society
      classification, termed "numbered"; or (3) neither the "grouped" nor "numbered"
      classification, termed "non-grouped". RESULTS: A total of 50 reports (45
      neoplastic, five chronic pancreatitis) were studied, 11 with non-grouped LNs, 14
      with grouped LNs, and 25 with numbered LNs, including the five inflammatory
      cases. A median of 7.0 LNs was found in non-grouped cases, a significantly lower
      number than in the grouped cases (median, 12.0; Mann-Whitney U, p < 0.039) and
      numbered cases (median, 17.0; p < 0.0001). There was no significant difference in
      the LN yield between grouped and numbered cases (p = 0.1066). LNs were found most
      frequently in the inferior, posterior pancreaticoduodenal, and infrapyloric
      regions. CONCLUSIONS: A detailed knowledge of the anatomical distribution of LNs
      in pancreatoduodenectomy resection specimens significantly improves LN yield. It
      is suggested that illustrations of LN sites in resection specimens should be
      included in pathology guidelines/proformas to improve LN detection and,
      therefore, pathological prognostic data.

PMID- 11577122
TI  - Conversion to core biopsy in preoperative diagnosis of breast lesions: is it
      justified by results?
AB  - AIMS: In recent years there has been increased use of core biopsy for the
      preoperative diagnosis of screen detected and symptomatic breast lesions. The aim
      of this study was to compare the quality assessment parameters for preoperative
      diagnosis by fine needle aspiration cytology (FNAC) before conversion to core
      biopsy with those for core biopsy after conversion in screening and symptomatic
      practice. Accuracy of typing and grading of tumours on core biopsy was assessed.
      METHODS: Correlation of FNAC (C1-5) and core biopsy (B1-5) results (total of 1768
      cases) with subsequent available resection histology was performed for 473 FNAC
      samples in 1997/98, 349 core biopsies in 1998/99 performed in symptomatic
      practice, for 561 FNAC samples in 1997/98, and 385 core biopsies in 1998/99
      performed in screening. Quality assessment parameters were calculated using the
      methodology detailed in the National Health Service Breast Screening Programme
      guidelines for cytology practice. RESULTS: Increased absolute and complete
      specificity, lower inadequate rates, and lower suspicious rates were found for
      core biopsy compared with FNAC in both symptomatic and screening practice. Typing
      of tumours was attempted in 86.7% of core biopsies in symptomatic practice and
      was accurate in 93.6% (132 of 141 where type was stated). Grading of tumours was
      attempted in 63.5% of invasive carcinomas, with the provisional grade on core
      biopsy being confirmed on later histology in 75% of grade 1 cases, in 70% of
      grade 2 cases, and in 86% of grade 3 cases. No case provisionally graded as 1 was
      subsequently found to be grade 3 and no provisionally grade 3 case was found to
      be grade 1. CONCLUSION: Conversion to core biopsy for the preoperative diagnosis
      of breast lesions increases specificity and reduces inadequate and suspicious
      rates. Grading and typing of tumours and assessment of oestrogen receptor status
      by immunocytochemistry is also possible in core biopsy, thereby increasing
      diagnostic information available when considering treatment options.

PMID- 11577123
TI  - Malignant mesothelioma: a comparison of biopsy and postmortem material by light
      microscopy and immunohistochemistry.
AB  - AIMS: The diagnosis of malignant mesothelioma in pleural biopsies can be
      difficult. Survival is short and consequently many of these cases are submitted
      to necropsy to assist with medicolegal claims. This study compares the
      histological appearances and immunohistochemical profile of nine biopsy specimens
      with corresponding postmortem specimens. METHODS: Archival, formalin fixed,
      paraffin wax embedded material was obtained from nine biopsy and corresponding
      postmortem cases of malignant mesothelioma. The specimens were examined by light
      microscopy and stained with an immunohistochemical panel of 12 commercially
      available antibodies including CAM5.2, HBME-1, and Ber-EP4, and antibodies to
      thrombomodulin, calretinin, CD44H, WT-1, carcinoembryonic antigen, Leu-M1,
      epithelial membrane antigen and p53. RESULTS: There was greater variation in the
      range of histological appearances of mesotheliomas in postmortem specimens
      compared with biopsy specimens. There was also variability in the
      immunohistochemical staining pattern for certain antibodies including HBME-1, and
      Ber-EP4 and antibodies to calretinin, CD44H, WT-1, and p53. CONCLUSIONS: All
      available information should be taken into account in the histological diagnosis
      of malignant mesothelioma. Interpretation of the immunohistochemical profile
      should be regarded with some caution when only postmortem material is available.
      When reporting a postmortem case of suspected mesothelioma, the pathologist
      should seek to review all available biopsy material in conjunction with the
      necropsy.

PMID- 11577124
TI  - Colonisation density and topographic localisation of Helicobacter pylori do not
      depend on the cagA status.
AB  - AIMS: To explore the correlation between the cagA status of Helicobacter pylori
      and the density and topographic localisation of H pylori. METHODS: Gastric antral
      biopsy specimens were taken from 716 consecutive patients, including 293 H pylori
      positive patients (124 men, 169 women; mean age, 52.6 years; range, 12-87). A
      serum sample was taken for determination of IgG anti-CagA antibodies (sensitivity
      of 94.4% and specificity of 92.5%). The density of H pylori was assessed
      semiquantitatively (grades I-IV) in biopsy specimens stained with the modified
      Giemsa stain. Topographic localisation was classified as follows: score A, H
      pylori closely attached to the mucosa; score B, H pylori attached to the mucosa
      and in the mucus; and score C, H pylori solely in the mucus. RESULTS: CagA
      antibodies were present in 154 (52.5%) of the patients. There was no significant
      difference in colonisation density and cagA status: grade I, 23 (14%); grade II,
      78 (50.6%); grade III, 42 (27.5%); and grade IV, 11 (7.2%) in the cagA(+) strains
      and 29 (21.2%), 57 (40.8%), 38 (27%), and 15 (11%), respectively, in the cagA(-)
      strains. There was no difference in topographic localisation between cagA(+) and
      cagA(-)H pylori. Mean anti-CagA titres were 0.84, 0.84, 0.89, and 0.73 in
      patients with grades I-IV bacterial density, respectively. CONCLUSION: Antibody
      titres do not correlate with H pylori density and there is no difference in
      density between cagA(+) and cagA(-)H pylori strains. In addition there is no
      difference in topographic localisation between cagA(+) and cagA(-) H pylori
      strains.

PMID- 11577125
TI  - Helicobacter heilmannii gastritis: a histological and immunohistochemical trait.
AB  - AIM: Biopsies of the gastric antrum were reviewed over a period of 10 years to
      determine the prevalence of Helicobacter heilmannii in symptomatic subjects from
      this geographical area and to relate its presence to distinctive
      histopathological and immunohistochemical features. METHODS: Biopsies from 7926
      symptomatic patients were reviewed. Ten serial sections were stained with
      haematoxylin and eosin for conventional histology. Another 10 sections were
      stained with the Gram method for spiral bacteria. When H heilmannii was
      suspected, 10 additional serial sections were stained with methylene blue to
      obtain homogeneous colouring. An equal number of sections from patients affected
      by isolated H heilmannii or H pylori gastritis were analysed by
      immunohistochemistry to evaluate lymphoid aggregate/mucosal lymphocyte clonality
      (CD20 and CD3) and tumour necrosis factor alpha (TNF-alpha) in stromal cells.
      RESULTS: The prevalence of H heilmannii was 0.1% (eight of 7926), whereas H
      pylori was present in 60.7% of patients (4813 of 7926). In two of the eight H
      heilmannii positive patients both helicobacters were found. In all subjects
      infected by H heilmannii only, distinctive histology (lymphocyte exudation into
      gastric foveolae) was seen. Lymphoid aggregates, chronic mucosal inflammation
      with patchy activity, and the absence of epithelial mucus depletion were regular
      features of H heilmannii gastritis. Immunohistochemistry did not reveal different
      lymphocyte clonal patterns between H pylori and H heilmannii gastritis: CD20
      positive cells were predominant in the centre of aggregates and mucosal
      infiltrates, whereas CD3 positive cells were prevalent at the periphery of
      follicles. Only H pylori gastritis showed a significant increase in TNF-alpha
      positive stromal cells. CONCLUSION: These data suggest that an unusual lymphocyte
      reaction, with the tendency to invade the foveolar lumen, is a distinctive
      histopathological aspect of H heilmannii chronic gastritis, although further
      studies in a larger series are necessary to confirm this fact. Nevertheless,
      lymphocyte clones do not differ qualitatively from those found in H pylori
      infection. Moreover, compared with H heilmannii, H pylori provokes a more intense
      release of TNF-alpha, suggesting that different inflammatory responses exist to
      these two organisms.

PMID- 11577126
TI  - High quality RNA isolation from tumours with low cellularity and high
      extracellular matrix component for cDNA microarrays: application to
      chondrosarcoma.
AB  - AIMS: High quality RNA isolation from cartilaginous tissue is considered
      difficult because of relatively low cellularity and the abundance of
      extracellular matrix rich in glycosaminoglycans and collagens. Given the growing
      interest and technical possibilities to study RNA expression at a high throughput
      level, research on tissue with these characteristics is hampered by the lack of
      an efficient method for obtaining sufficient amounts of high quality RNA.
      METHODS: This paper presents a robust protocol combining two RNA isolation
      procedures, based on a combination of Trizol and RNA specific columns, which has
      been developed to obtain high molecular weight RNA from fresh frozen and stored
      tissue of normal cartilage and cartilaginous tumours. Using this method, RNA was
      isolated from normal cartilage, peripheral chondrosarcoma, and central
      chondrosarcoma. RESULTS: The yields ranged from 0.1 to 0.5 microg RNA/mg tissue.
      RNA isolated with this method was stable and of high molecular weight. RNA
      samples from normal cartilage and from two chondrosarcomas isolated using this
      method were applied successfully in cDNA microarray experiments. The number of
      genes that give interpretable results was in the range of what would be expected
      from microarray results obtained on chondrosarcoma cell line RNA. Signal to noise
      ratios were good and differential expression between tumour and normal cartilage
      was detectable for a large number of genes. CONCLUSION: With this newly developed
      isolation method, high quality RNA can be obtained from low cellular tissue with
      a high extracellular matrix component. These procedures can also be applied to
      other tumour material.

PMID- 11577127
TI  - Transthyretin values correlate with mucosal recovery in patients with coeliac
      disease taking a gluten free diet.
AB  - AIMS: To assess changes in indicators of nutrition and iron deficiency as
      possible non-invasive markers of mucosal recovery in patients with coeliac
      disease on a gluten free diet. METHODS: Concentrations of transthyretin, retinol
      binding protein, soluble transferrin receptor, IgA anti-gliadin, and IgA anti
      transglutaminase, and titres of IgA anti-endomysial antibody were measured in 36
      newly diagnosed adult patients with coeliac disease and duodenal villous atrophy
      before (T0) and after one year (T1) on a gluten free diet. Duodenal biopsies
      taken at T0 and T1 were compared and graded as no improvement (no change in
      initial grade of villous atrophy) or improvement. RESULTS: Twenty two patients
      showed histological improvement and 14 showed no improvement. Transthyretin
      values increased in all patients with mucosal improvement and decreased in all
      patients showing no improvement. However, transthyretin values did not correlate
      with the degree of villous atrophy at T0 and T1 when assessed separately. Changes
      in retinol binding protein and soluble transferrin receptor values did not
      correlate with mucosal improvement. Coeliac disease associated antibodies (to
      gliadin, endomysium, and transglutaminase) decreased in most patients between T0
      and T1, irrespective of mucosal recovery. CONCLUSIONS: Serial but not single
      measurements of transthyretin may be used as a non-invasive test to monitor
      mucosal recovery and therefore reduce the need for, or frequency of, follow up
      biopsies in treated patients with coeliac disease.

PMID- 11577128
TI  - Wegener's granulomatosis presenting as acute suppurative interstitial nephritis.
AB  - A 78 year old man presented with acute renal failure following a prolonged
      respiratory illness. A renal biopsy demonstrated severe suppurative interstitial
      nephritis with normal glomeruli. After nine weeks of antibiotics he remained
      anuric and a second biopsy demonstrated pauci-immune, necrotising
      glomerulonephritis. His subsequent clinical course was consistent with a
      diagnosis of Wegener's granulomatosis and antineutrophil cytoplasmic antibodies
      (ANCA) were detected. This is the first reported case of Wegener's granulomatosis
      presenting with an isolated tubulointerstitial lesion.

PMID- 11577129
TI  - Simultaneous occurrence of Epstein-Barr virus associated Hodgkin's disease and
      HHV-8 related multicentric Castleman's disease: a fortuitous event?
AB  - Previous serological or molecular studies by means of the polymerase chain
      reaction have failed to show an association between classic Hodgkin's disease
      (HD) and human herpesvirus 8 (HHV-8). Using immunohistochemistry, this study re
      examines (with anti-LNA1 antibody) the possible association of HHV-8 with HD,
      particularly in human immunodeficiency virus (HIV) infected patients. HHV-8 was
      not detected in the Reed Sternberg cells of the cases examined (33 HIV negative
      and 17 HIV positive), thus confirming the lack of involvement of HHV-8 in HD.
      Interestingly, a case of HHV-8 positive multicentric Castleman's disease was
      associated with Epstein-Barr virus positive HD in the same lymph node, which was
      probably a fortuitous occurrence.

PMID- 11577130
TI  - Fatal acute myocarditis in an infant with human herpesvirus 6 infection.
AB  - A 5 month old girl had typical clinical features of acute myocarditis just after
      the febrile period of exanthem subitum and died immediately. She had been
      healthy, with normal development, and there was no family history of particular
      note. Myocardial postmortem findings were compatible with acute myocarditis.
      Although the isolation of human herpesvirus 6 (HHV-6) was not attempted, positive
      IgM antibody to HHV-6 was detected in the patient's serum. Moreover, HHV-6
      variant B DNA was detected in several tissues, including myocardium, by the
      polymerase chain reaction (PCR). In contrast, antibody responses to human
      herpesvirus 7, another causal agent of exanthem subitum, were not found, and
      enteroviral RNA was not detected in myocardial tissues by reverse transcription
      PCR. Apoptotic changes were seen in infiltrating cells within the myocardial
      tissues by means of the TUNEL method. HHV-6 antigen was not detected in several
      tissues (including myocardium) by immunohistochemical analysis. In conclusion,
      HHV-6 may have been the causative agent of fatal acute myocarditis in this
      infant.

PMID- 11577131
TI  - Massive acute thymic haemorrhage and cerebral haemorrhage in an intrauterine
      fetal death.
AB  - Massive acute thymic haemorrhage in the neonate occurs extremely rarely and is
      associated with haemorrhagic disease of the newborn. A 30 year old woman with an
      unremarkable previous obstetric history presenting at 37 weeks and 4 days
      gestation with the complaint of loss of fetal movement was found to have a male
      fetus with findings at necropsy of massive acute thymic haemorrhage, acute
      intracranial haemorrhage, and hydrops fetalis. This is the first report of
      massive acute thymic haemorrhage in utero. Massive thymic haemorrhage should be
      added to the reported causes of lethal non-immunological hydrops.

PMID- 11577132
TI  - alpha-1 antitrypsin phenotypes by isoelectric focusing in a metropolitan southern
      Chinese population.
AB  - AIMS/BACKGROUND: alpha-1 antitrypsin (alpha1AT) is an abundant protease inhibitor
      in human plasma. Its phenotypic variability has been reported to be associated
      with pulmonary emphysema and chronic liver diseases. However, alpha1AT deficiency
      is an uncommon condition in the Chinese population. The aim of this study was to
      describe the phenotypic distribution of alpha1AT in a southern Chinese
      population. METHODS: A total of 1085 healthy blood donors underwent alpha1AT
      phenotyping by isoelectric focusing. RESULTS: Two thirds (66.1%) were homozygous
      for either M1 or M2, whereas 32.6% were heterozygous for two different M
      phenotypes. The frequency of allelic variants was only 0.007, and deficiency
      variants were absent. Compared with earlier studies on southern Chinese
      populations, this study found a lower frequency of M2, and a higher number of
      allelic variants, including E, L, N, P, and S. This phenomenon can be attributed
      to population migration and mixing. CONCLUSIONS: An understanding of the alpha1AT
      pattern is important for evaluating the predisposition of the population to
      selected clinical diseases.

PMID- 11577133
TI  - A retroperitoneal bronchogenic cyst: a rare cause of a mass in the adrenal
      region.
AB  - This report documents a bronchogenic cyst presenting as an adrenal tumour in a 51
      year old man with persistent epigastric pain. The cyst is regarded as a
      developmental abnormality of the primitive foregut, which typically occurs in the
      chest. Subdiaphragmatic, and retroperitoneal locations in particular, are
      unusual. The differential diagnosis of a bronchogenic cyst in the retroperitoneum
      includes cystic teratoma, bronchopulmonary sequestration, cysts of urothelial and
      mullerian origin, and other foregut cysts.

PMID- 11577134
TI  - Improved cultural detection of Burkholderia cepacia from sputum in patients with
      cystic fibrosis.
AB  - AIMS: To evaluate the sensitivity and specificity of two selective media for the
      isolation of Burkholderia cepacia from sputum specimens in patients with cystic
      fibrosis (CF). METHODS: In total, 149 expectorated sputum specimens from 113
      patients with CF (32 cepacia colonised patients and 81 non-cepacia colonised
      patients) attending three CF centres were examined for the presence of B cepacia
      on two selective media: (1) MAST selective agar, a commercially available
      selective medium widely used in the UK and (2) BCSA (B cepacia selective agar), a
      new medium recently described, which is used predominantly in North America.
      RESULTS: Burkholderia cepacia was isolated from 53 of 149 (35.6%) specimens
      examined, representing 32 of 113 (28.3%) patients, using both the MAST and BCSA
      media. Growth was most rapid on BCSA with all (53 of 53) isolates detectable
      after 48 hours, compared with 50 of the 53 isolates on MAST agar, with the
      remaining three isolates detectable at five days. Twenty eight contaminants were
      identified on MAST agar and 13 on BCSA agar; mainly Alcaligenes xylosoxidans and
      yeast on MAST agar and Flavobacterium indologenes on BCSA medium. BCSA was
      equivalent to MAST agar in its ability to isolate B cepacia from patients with CF
      with a history of B cepacia infection. CONCLUSIONS: The increased selectivity and
      reduced time to detection of BCSA makes it an attractive alternative to MAST.
      However, its present limited commercial availability in the UK may delay its use
      in routine diagnostic laboratories because of complications with media
      preparation and quality control.

PMID- 11577135
TI  - Are clinicians failing to supply adequate information when requesting a
      histopathological investigation?
AB  - AIMS: There is a perception among histopathologists that specimens are often
      received without adequate clinical details. This is the first study to determine
      the adequacy of information provided when histopathological investigations are
      requested. METHODS: Two thousand sequential requests for histological examination
      were assessed for adequacy and completeness. RESULTS: There was no significant
      difference in the demographic details supplied by physicians and surgeons.
      Clinical details were inadequate in 6.1% of cases: those from physicians were
      significantly more often adequate (98.7% v 90.6%) and more often included a
      diagnosis (74.4% v 38.8%) than those from surgeons. Physicians were more likely
      to supply their name and contact number but requests frequently lacked details of
      the sender. CONCLUSIONS: Specimens are infrequently received with inadequate
      demographic details, but clinical details and details of the sender are more
      often lacking. Education of clinical colleagues is required if pathologists are
      to manage the demand for the service.

PMID- 11577136
TI  - The use of a standard proforma in breast cancer reporting.
AB  - AIM: To determine whether the introduction of a standard reporting proforma has
      led to an improvement in the completeness of histopathology reports for breast
      cancer excision specimens. METHODS: A standard reporting proforma was designed
      using the Royal College of Pathologists' minimum dataset for breast cancer
      histopathology reports and the national histopathology reporting form of the
      National Health Service (NHS) breast screening programme. This was introduced
      into our department in June 1999, with reports generated from the proforma
      replacing the standard text reports. The pathological information contained in 50
      text reports issued before the introduction of the proforma and 50 reports
      generated using the proforma was compared with the minimum dataset and NHS breast
      screening programme guidelines. RESULTS: A general improvement in documentation
      of individual pathological features was noted after introduction of the proforma.
      This was most significant in relation to documentation of features, such as
      microcalcification and ductal carcinoma in situ. In addition, important features
      such as tumour grade, tumour size, and hormone receptor status were documented
      more frequently in the proforma group. There was an overall increase in the
      number of reports regarded as complete after introduction of the proforma.
      CONCLUSIONS: The introduction of a standard proforma led to a significant
      improvement in the completeness of breast cancer histopathology reports in this
      centre, but continued vigilance is needed to ensure that standards continue to
      improve.

PMID- 11577137
TI  - Time resolved fluorometric immunoassay, using europium labelled antihuman IgG,
      for the detection of human tetanus antitoxin in serum.
AB  - A time resolved fluorometric immunoassay (TRFIA) has been developed and compared
      with an in house enzyme linked immunosorbent assay (ELISA) and commercial ELISA
      (Bindazyme) for the detection of tetanus antitoxin in human sera. A panel of 132
      sera submitted for routine testing was used. Scatterplots showed a high degree of
      correlation between all three assays, although some divergence of results was
      apparent for low titre sera when comparing in house ELISA results with Bindazyme
      ELISA and TRFIA results. The TRFIA appeared to be more sensitive than the in
      house ELISA, and the Bindazyme assay compared well with the TRFIA. The intra
      assay precision of all three assays, in terms of percentage coefficient of
      variation (%CV), was between 2.0% and 4.0%. The interassay precision ranged from
      5% to 8% for the in house ELISA, 13% to 19% for the Bindazyme assay, and 11% to
      13% for TRFIA. Both Bindazyme and TRFIA assays were simple to perform, accurate,
      reproducible, and amenable to automation. A particular benefit of the TRFIA was
      its large dynamic range, enabling tetanus antitoxin values of 0.01 IU/ml to 50
      IU/ml to be measured with just one dilution of serum. TRFIA appears to be a
      useful serological technique worthy of further development.

PMID- 11577138
TI  - Size, volume, length and the control of the bacterial division cycle.

PMID- 11577142
TI  - Weak acid adaptation: the stress response that confers yeasts with resistance to
      organic acid food preservatives.

PMID- 11577143
TI  - FindTarget: software for subtractive genome analysis.
AB  - In silico subtractive/differential genome analysis is a powerful approach for
      identifying genus- or species-specific genes, or groups of genes that are
      responsible for a unique phenotype. By this method, one searches for genes
      present in one group of bacteria and absent in another group. A software package
      has been developed, named FindTarget, that has a user-friendly web interface to
      facilitate differential genome analysis. The user chooses the genomes to compare,
      the similarity criteria and the thresholds to decide if a gene has a counterpart
      in another genome. The searches are based on BLASTP comparisons of proteomes.
      FindTarget also includes access to sequences, coloured multiple alignments,
      phylogenetic trees of conserved proteins and links to public annotated databases
      which provide a means for validation of the results. To illustrate this approach,
      a FindTarget search for genes putatively involved in the specificity of cell
      envelope synthesis of Gram-negative bacteria is presented. The results show that
      most of the identified genes are clearly involved in cell wall processes,
      underlining the power of such an approach in general and that of FindTarget in
      particular.

PMID- 11577144
TI  - Adherence of Burkholderia cepacia to respiratory tract epithelial cells and
      inhibition with dextrans.
AB  - Adherence of Burkholderia cepacia to cells of the respiratory tract of patients
      with cystic fibrosis (CF) appears to be a necessary precondition for colonization
      and infection. To date, no effective anti-adhesive strategy has been devised for
      preventing B. cepacia infection in CF patients. It was found in this study that
      B. cepacia adhered to respiratory epithelial cells both in vitro and in vivo.
      However, strains with cable-like pili (Cbl) exhibited the typical clump formation
      on pneumocytes, whereas non-cable piliated strains predominantly showed single
      cell adherence. Dextrans (nominally 4000-10000 Da) significantly inhibited
      adhesion of B. cepacia to A549 pneumocytes. When compared on an equal weight
      basis, the nominally 10000 Da dextran was most inhibitory. A dose-dependent
      inhibitory effect (up to 80 mg ml(-1)) was observed for most strains. Dextran
      exerted less of an anti-adhesive effect on the two Cbl+ strains than on the
      others which were Cbl-. Dextrans appeared to block the adherence in a non
      specific fashion, as shown by the observations that the inhibitory effect was
      readily reversible and oligosaccharides composed of 2-4 glucose units with the
      same alpha-1,6 linkage were not inhibitory. The mean molecular masses of dextrans
      used in this study, as determined by gel filtration and MS, were approximately 10
      fold lower than those indicated by the manufacturers. Our data suggest that
      dextran of nominal molecular mass 4000 Da at a concentration of 40 mg ml(-1) (10
      mM according to manufacturer's quoted molecular mass) or more may be useful in
      patients with CF to prevent colonization and infection with B. cepacia.

PMID- 11577145
TI  - Prevalence of type III secretion genes in clinical and environmental isolates of
      Pseudomonas aeruginosa.
AB  - The type III secretion system of Pseudomonas aeruginosa transports four known
      effector proteins: ExoS, ExoT, ExoU and ExoY. However, the prevalence of the type
      III secretion system genes or the effector-encoding genes in clinical and
      environmental isolates of P. aeruginosa has not been well studied. Southern
      hybridization analyses and PCR were performed on over 100 P. aeruginosa isolates
      to determine the distribution of these genes. Clinical isolates were obtained
      from urine, endotracheal, blood and wound specimens, from the sputum of cystic
      fibrosis (CF) patients, and from non-hospital environmental sites. The popB gene
      was used as a marker for the presence of the large chromosomal locus encoding the
      type III secretion machinery proteins. Each isolate contained the popB gene,
      indicating that at least a portion of this large chromosomal locus was present in
      all isolates. Likewise, each isolate contained exoT-like sequences. In contrast,
      the exoS, exoU and exoY genes were variable traits. Overall, 72% of examined
      isolates contained the exoS gene, 28% contained the exoU gene, and 89% contained
      the exoY gene. Interestingly, an inverse correlation was noted between the
      presence of the exoS and exoU genes in that all isolates except two contained
      either exoS or exoU but not both. No significant difference in exoS, exoU or exoY
      prevalence was observed between clinical and environmental isolates or between
      isolates cultured from different disease sites except for CF respiratory
      isolates. CF isolates harboured the exoU gene less frequently and the exoS gene
      more frequently than did isolates from some of the other sites of infection,
      including the respiratory tract of patients without CF. These results suggest
      that the P. aeruginosa type III secretion system is present in nearly all
      clinical and environmental isolates but that individual isolates and populations
      of isolates from distinct disease sites differ in their effector genotypes. The
      ubiquity of type III secretion genes in clinical isolates is consistent with an
      important role for this system in human disease.

PMID- 11577146
TI  - The Pseudomonas aeruginosa acsA gene, encoding an acetyl-CoA synthetase, is
      essential for growth on ethanol.
AB  - Pseudomonas aeruginosa ATCC 17933 uses a pyrroloquinoline quinone-dependent
      ethanol oxidation system. Two mutants of P. aeruginosa, unable to grow on ethanol
      and showing no acetyl-CoA synthetase (ACS) activity under standard test
      conditions, were complemented by cosmid pTB3018. Subcloning led to the isolation
      of a gene which encodes a protein with high similarity to acetyl-CoA synthetases.
      Interruption of the putative acsA gene by a kanamycin-resistance cassette
      resulted in a mutant also unable to grow on ethanol and with very low residual
      acetyl-CoA-forming activity. Complementation by the wild-type allele of the acsA
      gene restored growth and led to the expression of ACS activity in excess of that
      of wild-type cells. In wild-type P. aeruginosa, ACS activity was induced upon
      growth on ethanol, 2,3-butanediol, malonate and acetate. The wild-type and
      mutants defective in ACS activity showed an active acetate kinase (ACK) under the
      growth conditions used; however, phosphotransacetylase (PTA) could not be
      detected. The data indicate that P. aeruginosa requires active acsA gene product
      for growth on ethanol.

PMID- 11577147
TI  - Functional assembly of two membrane-binding domains in listeriolysin O, the
      cytolysin of Listeria monocytogenes.
AB  - Listeriolysin O (LLO) is a major virulence factor secreted by the pathogenic
      Listeria monocytogenes and acts as pore-forming cytolysin. Based on sequence
      similarities between LLO and perfringolysin (PFO), the cytolysin from Clostridium
      perfringens of known crystallographic structure, two truncated LLO proteins were
      produced: LLO-d123, comprising the first three predicted domains, and LLO-d4, the
      last C-terminal domain. The two proteins were efficiently secreted into the
      culture supernatant of L. monocytogenes and were able to bind to cell membranes.
      Strikingly, when expressed simultaneously, the two secreted domains LLO-d123 and
      LLO-d4 reassembled into a haemolytically active form. Two in-frame linker
      insertions were generated in the hinge region between the d123 and d4 domains. In
      both cases, the insertion created a major cleavage site for proteolytic
      degradation and abolished cytolytic activity, which might suggest that the region
      connecting d123 and d4 participates in the interaction between the two portions
      of the monomer.

PMID- 11577148
TI  - Relationship between nucleic acid ratios and growth in Listeria monocytogenes.
AB  - Listeria monocytogenes is a pathogen whose distribution in a range of foodstuffs
      requires the development of methods for sensitive and rapid detection. Molecular
      biological methods usually rely on specific detection of L. monocytogenes rDNA
      directly amplified by the application of PCR to DNA extracts. Information on the
      metabolic status of L. monocytogenes populations would be valuable and can, in
      theory, be provided by quantitative detection of rRNA itself. Both fluorometry
      and oligonucleotide probe assays were applied to L. monocytogenes cultures to
      quantify RNA and DNA and produced more meaningful data than previous estimates
      for bacteria based on eukaryotic nucleic acid standards. In batch culture, the
      RNA-DNA ratio was found to be greatest at the end of exponential growth, after
      which RNA became degraded in accordance with the rapid decrease in viability.
      When the pH of the medium was controlled at neutrality, culture viability was
      dramatically extended and although RNA was degraded, intact DNA was maintained
      for the duration of the experiment. Ribosome numbers per cell were estimated to
      decrease from about 25000 observed during mid-exponential growth to about 600
      during stationary phase, under pH-controlled conditions. Like Escherichia coli,
      therefore, L. monocytogenes loses viability and rRNA rapidly once exponential
      growth has ceased in batch culture. However, much improved survival of a
      culturable L. monocytogenes population when pH is controlled has clear
      implications for the persistence of this species in buffered environments such as
      dairy products.

PMID- 11577149
TI  - Porins from Salmonella enterica serovar Typhimurium induce TNF-alpha, IL-6 and IL
      8 release by CD14-independent and CD11a/CD18-dependent mechanisms.
AB  - Lipopolysaccharide (LPS) of Gram-negative bacteria and several surface components
      of Gram-positive bacteria utilize CD14 and CD11a/18 as cellular receptors to
      induce expression and release of cytokines. Of the surface components of Gram
      negative bacteria, porins exhibit a biological activity similar to that of LPS.
      The results in this paper show that the mechanism of stimulation by porins of THP
      1 cells enriched in CD14 receptor after treatment with 1,25-dihydroxyvitamin D(3)
      (vitamin D(3)) is independent of this receptor, but is partially dependent on
      CD11a/18 integrins.

PMID- 11577150
TI  - Genomic analysis and growth-phase-dependent regulation of the SEF14 fimbriae of
      Salmonella enterica serovar Enteritidis.
AB  - Salmonella enterica serovar Enteritidis is a leading cause of food poisoning in
      the USA and Europe. Although Salmonella serovars share many fimbrial operons, a
      few fimbriae are limited to specific Samonella serovars. SEF14 fimbriae are
      restricted to group D Salmonella and the genes encoding this virulence factor
      were acquired relatively recently. Genomic, genetic and gene expression studies
      have been integrated to investigate the ancestry, regulation and expression of
      the sef genes. Genomic comparisons of the Salmonella serovars sequenced revealed
      that the sef operon is inserted in leuX in Salmonella Enteritidis, Salmonella
      Paratyphi and Salmonella Typhi, and revealed the presence of a previously
      unidentified 25 kb pathogenicity island in Salmonella Typhimurium at this
      location. Salmonella Enteritidis contains a region of homology between the
      Salmonella virulence plasmid and the chromosome downstream of the sef operon. The
      sef operon itself consists of four co-transcribed genes, sefABCD, and adjacent to
      sefD there is an AraC-like transcriptional activator that is required for
      expression of the sef genes. Expression of the sef genes was optimal during
      growth in late exponential phase and was repressed during stationary phase. The
      regulation was coordinated by the RpoS sigma factor.

PMID- 11577151
TI  - Genomic analysis of the erythromycin resistance element Tn5398 from Clostridium
      difficile.
AB  - Clostridium difficile is a nosocomial pathogen that causes a range of chronic
      intestinal diseases, usually as a result of antimicrobial therapy. Macrolide
      lincosamide-streptogramin B (MLS) resistance in C. difficile is encoded by the
      Erm B resistance determinant, which is thought to be located on a conjugative
      transposon, Tn5398. The 9630 bp Tn5398 element has been cloned and completely
      sequenced and its insertion site determined. Analysis of the resultant data
      reveals that Tn5398 is not a classical conjugative transposon but appears to be a
      mobilizable non-conjugative element. It does not carry any transposase or site
      specific recombinase genes, nor any genes likely to be involved in conjugation.
      Furthermore, using PCR analysis it has been shown that isolates of C. difficile
      obtained from different geographical locations exhibit heterogeneity in the
      genetic arrangement of both Tn5398 and their Erm B determinants. These results
      indicate that genetic exchange and recombination between these determinants
      occurs in the clinical and natural environment.

PMID- 11577152
TI  - Differentiation of Campylobacter species by AFLP fingerprinting.
AB  - The fluorescent amplified fragment length polymorphism (AFLP) fingerprinting
      method was tested for its ability to identify and subtype the most important
      Campylobacter species found in veterinary infections. Sixty-nine reference
      strains and 19 clinical isolates of Campylobacter jejuni subsp. jejuni,
      Campylobacter jejuni subsp. doylei, Campylobacter upsaliensis, Campylobacter
      coli, Campylobacter lari, Campylobacter fetus subsp. fetus, C. fetus subsp.
      venerealis, Campylobacter hyointestinalis subsp. hyointestinalis, C.
      hyointestinalis subsp. lawsonii, Campylobacter mucosalis, Campylobacter
      helveticus and Campylobacter sputorum were subjected to analysis. The topology of
      the dendrogram obtained by numerical analysis of the AFLP profiles did not
      reflect the phylogenetic relationships as derived from 16S rDNA sequence
      comparison. However, except for C. lari, AFLP analysis grouped the strains that
      belonged to the same genomic species into distinct clusters. C. lari strains were
      separated into two distinct AFLP groups, which corresponded with nalidixic-acid
      sensitive and -resistant variants of C. lari. These results correlated with data
      from whole-cell protein profiling. Within C. jejuni, C. hyointestinalis and C.
      fetus, strains could be identified at the subspecies level. AFLP analysis also
      allowed the subtyping of most species at the strain level. It is concluded that
      AFLP analysis is a valuable tool for concurrent identification of campylobacters
      at the species, subspecies and strain levels. In addition, the data confirm and
      extend previous reports showing that C. lari is a heterogeneous species that may
      comprise multiple taxa.

PMID- 11577153
TI  - Genetic diversity of Pasteurella multocida fowl cholera isolates as demonstrated
      by ribotyping and 16S rRNA and partial atpD sequence comparisons.
AB  - The genetic diversity of Pasteurella multocida, the aetiological agent of fowl
      cholera, was investigated. The strain collection comprised 69 clinical isolates
      representing a wide spectrum of hosts and geographic origin. The three type
      strains for the subspecies of P. multocida were also included. Avian isolates of
      P. multocida subsp. multocida and P. multocida subsp. septica did not represent
      separate lines by HpaII ribotyping and the two type strains of mammalian origin
      (porcine and cat bite) seemed to be representative of avian strains of P.
      multocida subspp. multocida and septica. By ribotyping, all P. multocida subsp.
      gallicida strains, except one chicken isolate and the type strain, clustered
      together. This indicated that the bovine type strain was not representative of
      this subspecies and that most strains of P. multocida subsp. gallicida are
      genetically related and may be distantly related to other P. multocida isolates,
      including those of avian origin. By 16S rRNA and atpD sequence comparisons of
      selected strains, including both P. multocida isolated from birds and mammals and
      selected distantly related Pasteurella species associated with birds and mammals,
      it was found that P. multocida is monophyletic. Extended DNA-DNA hybridizations
      are highly indicated since strains may exist which would connect the existing
      subspecies at species level. The considerable genetic diversity of P. multocida
      fowl cholera isolates is probably related to the clonal nature of this organism,
      resulting in many divergent lines.

PMID- 11577154
TI  - Fermentable-sugar-level-dependent regulation of leukotoxin synthesis in a
      variably toxic strain of Actinobacillus actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans, a Gram-negative periodontopathic bacterium,
      produces a leukotoxin belonging to the RTX family. The production of leukotoxin
      varies greatly among different strains of this species and under different
      culture conditions. A toxin-production-variable strain, 301-b, stably produces
      significant amounts of leukotoxin in anaerobic fructose-limited chemostat
      cultures, but does not do so in the presence of excess fructose. This
      communication describes the cloning and sequencing of the leukotoxin promoter
      region from 301-b, showing that this strain has a promoter region similar to that
      from strain 652, a moderately toxic strain. Northern blot analysis using a
      leukotoxin gene probe demonstrated that change in toxin production in response to
      the level of external fructose was due to alteration in the transcriptional level
      of the leukotoxin gene. Pulsing of fructose into the fructose-limited chemostat
      culture remarkably reduced the intracellular cAMP level from 40 pmol (mg dry wt
      cells)(-1) to 3.1 pmol (mg dry wt cells)(-1), which was restored when the culture
      was returned to fructose-limited conditions. Further, it was found that addition
      of external cAMP to the culture with excess fructose resulted in an apparent
      recovery of leukotoxin production. Taken together, these findings indicate that a
      cAMP-dependent mechanism, possibly a catabolite-repression-like system, may be
      involved in the regulation of leukotoxin production in this bacterium.

PMID- 11577155
TI  - The replicon of pSW800 from Pantoea stewartii.
AB  - A 2019 bp DNA fragment containing the replicon of pSW800 from Pantoea stewartii
      SW2 was cloned and characterized. This replicon contains two genes--repA and
      repB, which encode a 36.5 kDa replication initiation protein (RepA) and a peptide
      of 18 aa, respectively. These two genes overlap by 8 bases with repB situated
      upstream. The replicon also transcribes an antisense RNA (RNAI) that inhibits the
      expression of repA and repB. The ribosome-binding sequence (RBS) of repA is
      likely to be hidden in a stem-loop structure, inhibiting the translation of repA.
      Furthermore, translation of repB is likely to disrupt the stem-loop structure,
      which is one of the criteria allowing the translation of repA to begin. A
      mutagenesis study revealed that a sequence (5'-GCACGGG-3') located 111 nt
      upstream from repA is crucial; mutation of this sequence prevented the
      translation of repA. Additionally, this region and the stem-loop structure
      containing the RBS of repA may form an RNA pseudoknot. Results in this study
      demonstrate that a mechanism similar to that regulating plasmid replication in
      the IncB, IncIalpha and IncL/M groups also regulates pSW800 replication.

PMID- 11577156
TI  - Polycations increase the permeability of Mycobacterium vaccae cell envelopes to
      hydrophobic compounds.
AB  - Polycations [protamine, polymyxin B nonapeptide (PMBN) and polyethyleneimine
      (PEI)] have been shown to increase the cell wall permeability of Mycobacterium
      vaccae to highly hydrophobic compounds, as manifested in enhanced intracellular
      bioconversion of beta-sitosterol to 4-androsten-3,17-dione (AD) and 1,4
      androstadien-3,17-dione (ADD), and cell sensitization to erythromycin and
      rifampicin. The quantity of AD(D) formed per biomass unit was twice as high in
      the presence of PMBN and PEI, and three times higher with protamine. The
      sensitization factor, i.e. the MIC(50) ratio of the control bacteria to those
      exposed to polycations, ranged from 4 to 16, depending on the
      polycation/antibiotic combination. Non-covalently bound free lipids were
      extracted from the control and polycation-treated cells and fractionated with the
      use of chloroform, acetone and methanol. Chloroform- and acetone-eluted fractions
      (mainly neutral lipids and glycolipids, respectively) showed significant
      polycation-induced alterations in their quantitative and qualitative composition.
      The fatty acid profile of neutral lipids was reduced in comparison to control,
      whereas acetone-derived lipids were characterized by a much higher level of
      octadecenoic acid (C(18:1)) and a considerably lower content of docosanoic acid
      (C(22:0)), the marker compound of mycolate-containing glycolipids. Methanol
      eluted fractions remained unaltered. Cell-wall-linked mycolates obtained from
      delipidated cells were apparently unaffected by the action of polycations, as
      judged from the TLC pattern of mycolic acid subclasses, the mean weight of
      mycolate preparations and the C(22:0) acid content in the mycolates, determined
      by GC/MS and pyrolysis GC. The results suggest the involvement of the components
      of non-covalently bound lipids in the outer layer in the M. vaccae permeability
      barrier.

PMID- 11577157
TI  - Fluoranthene metabolism in Mycobacterium sp. strain KR20: identity of pathway
      intermediates during degradation and growth.
AB  - Mycobacterium sp. strain KR20, which was isolated from a polycyclic aromatic
      hydrocarbon (PAH) contaminated soil of a former gaswork plant site, metabolized
      about 60% of the fluoranthene added (0.5 mg ml(-1)) to batch cultures in mineral
      salts medium within 10 d at 20 degrees C. It thereby increased its cell number
      about 30-fold and produced at least seven metabolites. Five metabolites, namely
      cis-2,3-fluoranthene dihydrodiol, Z-9-carboxymethylene-fluorene-1-carboxylic
      acid, cis-1,9a-dihydroxy-1-hydro-fluorene-9-one-8-carboxylic acid, 4
      hydroxybenzochromene-6-one-7-carboxylic acid and benzene-1,2,3-tricarboxylic
      acid, could be identified by NMR and MS spectroscopic techniques and ascribed to
      an alternative fluoranthene degradation pathway. Besides fluoranthene, the
      isolate could not use any of the PAHs tested as a sole source of carbon and
      energy.

PMID- 11577158
TI  - The transcriptional activator NhaR is responsible for the osmotic induction of
      osmC(p1), a promoter of the stress-inducible gene osmC in Escherichia coli.
AB  - Two overlapping promoters, osmC(p1) and osmC(p2), direct the transcription of the
      osmC gene of Escherichia coli. The proximal promoter, osmC(p2), is induced upon
      entry into stationary phase under the control of Esigma(s), the RNA polymerase
      that uses the sigma(s) (RpoS) sigma factor. Transcription from the distal
      promoter, osmC(p1), is independent of sigma(s). Previous analysis demonstrated
      that the osmolarity of the growth medium modulates expression of both promoters.
      The use of an E. coli genomic library showed that the cloned nhaR gene was able
      to stimulate transcription of an osmC-lac reporter fusion. NhaR is a positive
      regulator of the LysR family, previously identified as an activator of nhaA, a
      gene encoding a Na+/H+ antiporter involved in adaptation to Na+ and alkaline pH
      in E. coli and other enteric bacteria. NhaR was shown to activate only the
      expression of osmC(p1) and to be necessary for the induction of this promoter by
      LiCl, NaCl and sucrose. Therefore, activation by NhaR is responsible for the
      osmotic induction of osmC(p1). In contrast to its action on nhaA, NhaR activation
      of osmC(p1) is independent of H-NS. Activation of osmC(p1) by NhaR requires a
      site located just upstream of the atypical -35 region of the promoter.

PMID- 11577159
TI  - Acinetobacter baumannii has two genes encoding glutathione-dependent formaldehyde
      dehydrogenase: evidence for differential regulation in response to iron.
AB  - The adhC1 gene from Acinetobacter baumannii 8399, which encodes a glutathione
      dependent formaldehyde dehydrogenase (GSH-FDH), was identified and cloned after
      mapping the insertion site of Tn3-HoHo1 in a recombinant cosmid isolated from a
      gene library. Sequence analysis showed that this gene encodes a protein
      exhibiting significant similarity to alcohol dehydrogenases in bacterial, yeast,
      plant and animal cells. The expression of the adhC1 gene was confirmed by the
      detection of GSH-FDH enzyme activity in A. baumannii and Escherichia coli cells
      that expressed the cloned gene. However, the construction and analysis of an A.
      baumannii 8399 adhC1::Tn3-HoHo1 isogenic derivative revealed the presence of
      adhC2, a second copy of the gene encoding GSH-FDH activity. Enzyme assays and
      immunoblot analysis showed that adhC2 encodes a 46.5 kDa protein that is produced
      in similar amounts under iron-rich and iron-limited conditions. In contrast, the
      expression of adhC1, which encodes a 45 kDa protein with GSH-FDH activity, is
      induced under iron limitation and repressed when the cells are cultured in the
      presence of free inorganic iron. The differential expression of adhC1 is
      controlled at the transcriptional level and mediated through the Fur iron
      repressor protein, which has potential binding sites within the promoter region
      of this adhC copy. The expression of both adhC copies is significantly enhanced
      by the presence of sub-inhibitory concentrations of formaldehyde in the culture
      media. Examination of different A. baumannii isolates indicates that they can be
      divided into two groups based on the type of GSH-FDH they produce. One group
      contains only the constitutively expressed 46.5 kDa protein, whilst the other
      produces this GSH-FDH type in addition to the iron-regulated isoenzyme. Further
      analysis showed that the presence and expression of the two adhC genes does not
      confer resistance to exogenous formaldehyde, nor does it enable it to utilize
      methylated compounds as a sole carbon source when cultured under iron-rich as
      well as iron-deficient conditions.

PMID- 11577160
TI  - The gene cluster for chloramphenicol biosynthesis in Streptomyces venezuelae
      ISP5230 includes novel shikimate pathway homologues and a monomodular non
      ribosomal peptide synthetase gene.
AB  - Regions of the Streptomyces venezuelae ISP5230 chromosome flanking pabAB, an
      amino-deoxychorismate synthase gene needed for chloramphenicol (Cm) production,
      were examined for involvement in biosynthesis of the antibiotic. Three of four
      ORFs in the sequence downstream of pabAB resembled genes involved in the
      shikimate pathway. BLASTX searches of GenBank showed that the deduced amino acid
      sequences of ORF3 and ORF4 were similar to proteins encoded by monofunctional
      genes for chorismate mutase and prephenate dehydrogenase, respectively, while the
      sequence of the ORF5 product resembled deoxy-arabino-heptulosonate-7-phosphate
      (DAHP) synthase, the enzyme that initiates the shikimate pathway. A relationship
      to Cm biosynthesis was indicated by sequence similarities between the ORF6
      product and membrane proteins associated with Cm export. BLASTX searches of
      GenBank for matches with the translated sequence of ORF1 in chromosomal DNA
      immediately upstream of pabAB did not detect products relevant to Cm
      biosynthesis. However, the presence of Cm biosynthesis genes in a 7.5 kb segment
      of the chromosome beyond ORF1 was inferred when conjugal transfer of the DNA into
      a blocked S. venezuelae mutant restored Cm production. Deletions in the 7.5 kb
      segment of the wild-type chromosome eliminated Cm production, confirming the
      presence of Cm biosynthesis genes in this region. Sequencing and analysis located
      five ORFs, one of which (ORF8) was deduced from BLAST searches of GenBank, and
      from characteristic motifs detected in alignments of its deduced amino acid
      sequence, to be a monomodular nonribosomal peptide synthetase. GenBank searches
      did not identify ORF7, but matched the translated sequences of ORFs 9, 10 and 11
      with short-chain ketoreductases, the ATP-binding cassettes of ABC transporters,
      and coenzyme A ligases, respectively. As has been shown for ORF2, disrupting
      ORF3, ORF7, ORF8 or ORF9 blocked Cm production.

PMID- 11577161
TI  - The Chryseobacterium meningosepticum PafA enzyme: prototype of a new enzyme
      family of prokaryotic phosphate-irrepressible alkaline phosphatases?
AB  - Chryseobacterium meningosepticum is an aerobic Gram-negative rod widely
      distributed in natural environments. Unlike many bacteria, it produces a
      phosphate-irrepressible periplasmic alkaline phosphatase (AP). This work
      describes cloning of the gene encoding that enzyme from C. meningosepticum CCUG
      4310 (NCTC 10585), and preliminary characterization of its product. The gene,
      named pafA, encodes a protein (PafA) of 546 amino acids with a calculated
      molecular mass of the mature peptide of 58682 Da. PafA exhibits high sequence
      identity with the PhoV AP of Synechococcus PCC 7942 (49.9% identity) and with the
      Cda Ca(2+)-dependent ATPase of Myroides odoratus (51.9% identity), while being
      more distantly related to the PhoD AP of Zymomonas mobilis (22.1% identity) and
      to the PhoA AP of Escherichia coli (14.0% identity). PafA was partially purified;
      it exhibits optimal activity at pH 8.5 and is active towards a broad spectrum of
      substrates including both phosphomonoesters and ATP, with preferential activity
      for the latter compound. The present findings allow definition of a new family of
      APs including 60 kDa, periplasmic enzymes whose expression is not influenced by
      freely available P(i) in the medium. Moreover, PafA can be considered an
      evolutionary intermediate between Ca(2+)-ATPase of M. odoratus and the APs PhoV
      of Synechococcus PCC 7942 and PhoD of Z. mobilis.

PMID- 11577162
TI  - Regulation of the gtfBC and ftf genes of Streptococcus mutans in biofilms in
      response to pH and carbohydrate.
AB  - Streptococcus mutans produces a number of extracellular sucrose-metabolizing
      enzymes that contribute to the ability of the organism to cause dental caries,
      including three glucosyltransferases, the products of the gtfB, gtfC and gtfD
      genes, and a fructosyltransferase, encoded by the ftf gene. To better understand
      the regulation of the expression of these genes under environmental conditions
      that more closely mimic those in dental plaque, two strains of S. mutans
      harbouring fusions of the gtfBC (SMS102) and ftf (SMS101) promoters to a
      chloramphenicol acetyltransferase (CAT) gene were examined in biofilms formed in
      vitro. The strains were grown in a Rototorque biofilm reactor in a tryptone-yeast
      extract-sucrose medium. CAT specific activity in biofilm cells was measured at
      quasi-steady state or following additions of 25 mM sucrose or glucose, with or
      without pH control. After approximately 10 generations of biofilm growth, the ftf
      and gtfBC genes of S. mutans were found to be expressed at levels different from
      those reported for planktonic cells growing under otherwise similar conditions.
      The expression of these genes was induced by the addition of sucrose to the quasi
      steady-state cultures. Expression of the gtfBC genes was influenced by
      environmental pH, since CAT specific activities in quasi-steady-state biofilms of
      strain SMS102 grown without pH control were twice those produced by cells grown
      with pH control. Moreover, addition of glucose to quasi-steady-state biofilms
      resulted in increased expression of the gtfBC-cat fusion, although the magnitude
      of the induction was less than that seen with sucrose. The effect of pH on ftf
      expression was negligible. A modest and transient induction of ftf was observed
      in biofilms pulsed with excess glucose and the kinetics and level of induction of
      ftf by excess carbohydrate were dependent on the pH of the biofilms. This study
      demonstrates that the type and amount of carbohydrate and the environmental pH
      have a major influence on transcription of the gtfBC and ftf genes when the
      organisms are growing in biofilms, and provides evidence for previously
      undisclosed regulatory circuits for exopolysaccharide gene expression in S.
      mutans.

PMID- 11577163
TI  - New aspects of the glucose activation of the H(+)-ATPase in the yeast
      Saccharomyces cerevisiae.
AB  - The glucose-induced activation of plasma membrane ATPase from Saccharomyces
      cerevisiae was first described by Serrano in 1983. Many aspects of this signal
      transduction pathway are still obscure. In this paper, evidence is presented for
      the involvement of Snf3p as the glucose sensor related to this activation
      process. It is shown that, in addition to glucose detection by Snf3p, sugar
      transport is also necessary for activation of the ATPase. The participation of
      the G protein, Gpa2p, in transducing the internal signal (phosphorylated sugars)
      is also demonstrated. Moreover, the involvement of protein kinase C in the
      regulation of ATPase activity is confirmed. Finally, a model pathway is presented
      for sensing and transmission of the glucose activation signal of the yeast H(+)
      ATPase.

PMID- 11577164
TI  - Biochemical events leading to the diversion of carbon into storage lipids in the
      oleaginous fungi Mucor circinelloides and Mortierella alpina.
AB  - The biochemical events associated with the onset of lipid accumulation in Mucor
      circinelloides and Mortierella alpina, under conditions of nitrogen-limited
      growth, have been elucidated; they differ in key aspects from those described in
      oleaginous yeasts. The NAD+:isocitrate dehydrogenases of Mc. circinelloides and
      Mort. alpina were not absolutely dependent on AMP for activity. Furthermore,
      changes in the cellular adenine nucleotide pools and energy charge were different
      from those reported for oleaginous yeasts. In Mc. circinelloides ATP, ADP and AMP
      concentrations all decreased by 50% after nitrogen limitation, leading to a
      constant energy charge at the expense of the size of the total adenylate pool.
      Pyruvate carboxylase in Mc. circinelloides was cytosolic, having implications for
      the organization of lipid synthesis in filamentous fungi. As a result of the data
      obtained, a revised and more concerted mechanism for the initiation of storage
      lipid accumulation is put forward for filamentous fungi.

PMID- 11577165
TI  - Cytochrome c oxidase contains an extra charged amino acid cluster in a new type
      of respiratory chain in the amino-acid-producing Gram-positive bacterium
      Corynebacterium glutamicum.
AB  - The membranes from Corynebacterium glutamicum cells contain a hydrophobic di-haem
      C protein as the cytochrome c subunit of the new type of cytochrome bc complex
      (complex III in the respiratory chain) encoded by the qcrCAB operon [Sone, N.,
      Nagata, K., Kojima, H., Tajima, J., Kodera, Y., Kanamaru, T., Noguchi, S. &
      Sakamoto, J. (2001). Biochim Biophys Acta 1503, 279-290]. To characterize complex
      IV, cytochrome c oxidase and its structural genes were isolated. The oxidase is
      of the cytochrome aa(3) type, but mass spectrometry indicated that the haem is
      haem As, which contains a geranylgeranyl side-chain instead of a farnesyl group.
      The enzyme is a SoxM-type haem-copper oxidase composed of three subunits. Edman
      degradation and mass spectrometry suggested that the N-terminal signal sequence
      of subunit II is cleaved and that the new N-terminal cysteine residue is
      diacylglycerated, while neither subunit I nor subunit III is significantly
      modified. The genes for subunits II (ctaC) and III (ctaE) are located upstream of
      the qcrCAB operon, while that for subunit I (ctaD) is located separately. The
      oxidase showed low enzyme activity with extrinsic substrates such as cytochromes
      c from horse heart or yeast, and has the Cu(A)-binding motif in its subunit II. A
      prominent structural feature is the insertion of an extra charged amino acid
      cluster between the beta2 and beta4 strands in the substrate-binding domain of
      subunit II. The beta2-beta4 loop of this oxidase is about 30 residues longer than
      that of major cytochrome c oxidases from mitochondria and proteobacteria, and is
      rich in both acidic and basic residues. These findings suggest that the extra
      charged cluster may play a role in the interaction of the oxidase with the
      cytochrome c subunit of the new type of bc complex.

PMID- 11577166
TI  - The lactococcal secondary multidrug transporter LmrP confers resistance to
      lincosamides, macrolides, streptogramins and tetracyclines.
AB  - The active efflux of toxic compounds by (multi)drug transporters is one of the
      mechanisms that bacteria have developed to resist cytotoxic drugs. The authors
      describe the role of the lactococcal secondary multidrug transporter LmrP in the
      resistance to a broad range of clinically important antibiotics. Cells expressing
      LmrP display an increased resistance to the lincosamide, streptogramin,
      tetracycline and 14- and 15-membered macrolide antibiotics. The streptogramin
      antibiotic quinupristin, present in the fourth-generation antibiotic RP 59500,
      can inhibit LmrP-mediated Hoechst 33342 transport, but is not transported by
      LmrP, indicating that quinupristin acts as a modulator of LmrP activity. LmrP
      expressing Lactococcus lactis cells in which a proton-motive force is generated
      accumulate significantly less tetracycline than control cells without LmrP
      expression. In contrast, LmrP-expressing and control cells accumulate equal
      amounts of tetracycline in the absence of metabolic energy. These findings
      demonstrate that the increased antibiotic resistance in LmrP-expressing cells is
      a result of the active extrusion of antibiotics from the cell.

PMID- 11577167
TI  - Molecular genetics of solid tumours: translating research into clinical practice.
      What we could do now: breast cancer.
AB  - Breast cancer is a common solid malignancy in women. Over the past decade, much
      progress has been made in understanding the biology of breast cancer. The use of
      molecular and immunohistochemical techniques is providing insights that will
      allow us to tailor the management of patients with breast cancer. In this review,
      progress in the understanding of lobular carcinoma in situ and atypical ductal
      hyperplasia, the use of the molecular marker CerbB2, and information gained from
      the morphological analysis of tumours arising in patients with BRCA1 and BRCA2
      mutations is discussed.

PMID- 11577169
TI  - Calprotectin inhibits matrix metalloproteinases by sequestration of zinc.
AB  - BACKGROUND/AIMS: Calprotectin, a 36 kDa protein present in neutrophil cytoplasm,
      has antimicrobial and apoptosis inducing activities, which are reversed by the
      addition of zinc. Matrix metalloproteinases (MMPs), a family of zinc dependent
      enzymes, are important in many normal biological processes including embryonic
      development, angiogenesis, and wound healing, but also pathological processes
      such as inflammation, cancer, and tissue destruction. The aim of this study was
      to investigate whether calprotectin can inhibit MMP activity, and whether such
      inhibition could be overcome by the addition of zinc. METHODS: MMP activity was
      measured by the degradation of substrates precoated on to microwells, and
      visualised by Coomassie blue staining of residual substrate. Seven
      metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, and MMP-13) were
      tested against two substrates: gelatin and alpha-casein. RESULTS: All MMPs except
      MMP-1 were active against gelatin, whereas MMP-7 was the only enzyme active
      against alpha-casein. The addition of calprotectin inhibited the activity of all
      the MMPs, but different concentrations of the protein, from 0.3 microM to >
      11microM, were necessary to produce a 50% inhibition of the MMPs. Inhibition by
      calprotectin was largely overcome by the addition of zinc. CONCLUSIONS: The
      findings suggest that calprotectin inhibits MMPs by sequestration of zinc. The
      data also suggest that MMPs have different affinities for zinc and that
      calprotectin has a lower zinc affinity than the MMPs.

PMID- 11577168
TI  - IGFs and IGFBPs: surrogate markers for diagnosis and surveillance of tumour
      growth?
AB  - Insulin-like growth factors (IGFs), IGF receptors, and IGF binding proteins
      (IGFBPs) constitute the IGF system. Comprehensive data indicate that these
      factors play a pivotal role in tumorigenesis. Epidemiological data indicate that
      cancer risk is associated with high serum IGF-I values. Because dysregulation of
      the IGF system is a frequent pattern in malignancy, IGFs/IGFBPs might represent
      novel tumour markers that could be useful both for diagnosis and surveillance.

PMID- 11577170
TI  - Inhibition of glioma cell growth and tumorigenic potential by CCN3 (NOV).
AB  - AIMS: To establish whether the ectopic expression of CCN3 (NOV) in glioma cells
      can interfere with their tumorigenic potential and assess its potential value in
      molecular medicine. METHODS: Glioma cell lines were used to assess whether
      differences in the degree of intracellular communication induced by the
      expression of the gap junction protein connexin 43 (Cx43) is related to the
      differential expression of CCN3 (NOV). The antiproliferative activity of rat CCN3
      (rCCN3; NOV) in glioma cells, has been assessed both in vitro and in vivo with
      glioma cell lines expressing different amounts of CCN3 (NOV). RESULTS: Upon
      ectopic expression of Cx43, the growth of C6 glioma cells is decreased. An
      increase of CCN3 (NOV) expression matches the reduced tumorigenic potential of
      these transfected cells. The localisation of CCN3 (NOV) is affected by the
      increased expression of Cx43 in the Cx-13 transfected cells, in which it is
      detected at areas of cell-cell contact. In a xenograft model, CCN3 (NOV)
      transfected glioma cells were found to induce tumours to a lesser degree than
      their parental counterparts, which do not express detectable amounts of CCN3
      (NOV). CONCLUSIONS: Previous observations had suggested an inverse relation
      between CCN3 (NOV) expression in glioma cells and their tumorigenicity. These
      results establish a direct association between the establishment of functional
      gap junctional intercellular communication and the expression of rCCN3 (NOV). In
      addition to a negative effect on murine and human cell growth, CCN3 (NOV) has
      antiproliferative activity on tumour cells in vivo. Thus, the antiproliferative
      activity of the CCN3 (NOV) protein might involve reorganisation of cellular
      contacts that play a crucial role in tumorigenesis. The antiproliferative
      activity of CCN3 (NOV) established in this work sets the stage for the potential
      use of CCN proteins in molecular oncology.

PMID- 11577171
TI  - Chromosome 3p allele loss in early invasive breast cancer: detailed mapping and
      association with clinicopathological features.
AB  - AIMS: Chromosome 3p allele loss is a frequent event in many common sporadic
      cancers including lung, breast, kidney, ovarian, and head and neck cancer. To
      analyse the extent and frequency of 3p allelic losses in T1N0 and T1N1 invasive
      sporadic breast cancer, 19 microsatellite markers spread along 3p were analysed
      in 40 such breast carcinomas with known clinicopathological parameters. METHODS:
      Loss of heterozygosity analysis was carried out using 3p microsatellite markers
      that were non-randomly distributed and chosen to represent regions that show
      hemizygous and/or homozygous losses in lung cancer (lung cancer tumour suppressor
      gene region 1 ( LCTSGR1) at 3p21.3 and LCTSGR2 at 3p12), and regions
      demonstrating suppression of tumorigenicity in breast, kidney, lung, and ovarian
      cancer. RESULTS: Allelic loss was seen at one or more loci in 22 of these
      clinically early stage sporadic breast tumours, but none had complete 3p allele
      loss. Several regions with non-overlapping deletions were defined, namely: (1) 18
      tumours showed loss at 3p21-22, a physical distance of 12 Mb; (2) 11 tumours
      showed loss at 3p12 within a physical distance of 1 Mb, this region is contained
      within LCTSGR2; (3) six tumours showed loss at 3p25-24, including the von Hippel
      Lindau (VHL) locus; (4) five tumours showed loss at 3p14.2, including the fragile
      histidine triad (FHIT) locus. CONCLUSIONS: This is the largest study to date
      defining the extent and range of 3p allelic losses in early stage invasive breast
      cancer and the results indicate that region 3p21-22 containing LCTSGR1 and a
      region at 3p12 within LCTSGR2 are the most frequent sites of 3p allelic loss in
      these breast carcinomas. This suggests that tumour suppressor genes located in
      these regions may play important roles in the development of breast cancer. There
      was an association between increasing 3p allelic loss and increasing tumour grade
      and loss of progesterone (p = 0.0098) and oestrogen (p = 0.0472) receptor
      expression, indicating a link between 3p allelic loss and the regulation of
      differentiation.

PMID- 11577172
TI  - IGF status is altered by tamoxifen in patients with breast cancer.
AB  - AIMS: An increased concentration of insulin-like growth factor 1 (IGF-1) is an
      independent risk factor for premenopausal breast cancer. Tamoxifen is thought
      initially to reduce concentrations of IGF-1 and increase concentrations of the
      IGF binding proteins. The aim of this study was to compare concentrations of IGF
      1, IGF binding protein 1 (IGF-BP1), and IGF-BP3 in patients with breast cancer (n
      = 14) with those seen in control subjects (n = 23) and to assess the effect of
      tamoxifen on IGF status in these patients. METHODS: Non-fasting blood samples
      were collected from patients with breast cancer before surgery and after nine,
      18, and 27 months of tamoxifen treatment. The baseline concentrations were
      compared with those of age and sex matched healthy control subjects. RESULTS: IGF
      1, IGF-BP3, and IGF-BP1 concentrations were not significantly different in cases
      and controls. Tamoxifen treatment significantly increased IGF-BP1 after 18 and 27
      months (baseline: mean, 21.6 ng/ml; SD, 16.6; 18 months: mean, 52.0 ng/ml; SD,
      41.8; p = 0.019; 27 months: mean, 40.7 ng/ml; SD, 24.9; p = 0.043) and IGF-BP3
      after nine, 18, and 27 months (baseline: mean, 3119 ng/ml; SD, 507; nine months:
      mean, 3673 ng/ml; SD, 476; p = 0.004; 18 months: mean, 3445 ng/ml; SD, 634; p =
      0.034; 27 months: 3409 ng/ml; SD, 501; p = 0.043) when compared with baseline
      values. IGF-1 was not altered significantly from baseline at any time point.
      However, the IGF-1 to IGF-BP3 ratio was significantly decreased at both nine and
      18 months (baseline: mean, 0.058; SD, 0.014; nine months: mean, 0.039; SD, 0.008;
      p = 0.033; 18 months: mean, 0.044; SD, 0.012; p = 0.01). This ratio was not
      significantly different from baseline at 27 months (mean, 0.054; SD, 0.01; p =
      0.08). CONCLUSIONS: Tamoxifen increases IGF-BP3 and IGF-BP1 concentrations. It
      also decreases the IGF-1 to IGF-BP3 ratio but this effect may be limited after
      long term use. Longer follow up, with larger numbers of patients, should
      determine when, and for how long, tamoxifen can reduce circulating IGF-1.

PMID- 11577173
TI  - Insulin-like growth factor 1 (IGF-1): a growth hormone.
AB  - AIM: To contribute to the debate about whether growth hormone (GH) and insulin
      like growth factor 1 (IGF-1) act independently on the growth process. METHODS: To
      describe growth in human and animal models of isolated IGF-1 deficiency (IGHD),
      such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and
      IGF-1 gene or GH receptor gene knockout (KO) mice. RESULTS: Since the description
      of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS
      are shorter (42-47 cm) than healthy babies (49-52 cm), suggesting that IGF-1 has
      some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30%
      smaller. The postnatal growth rate of patients with LS is very slow, the distance
      from the lowest normal centile increasing progressively. If untreated, the final
      height is 100-136 cm for female and 109-138 cm for male patients. They have
      acromicia, organomicria including the brain, heart, gonads, genitalia, and
      retardation of skeletal maturation. The availability of biosynthetic IGF-1 since
      1988 has enabled it to be administered to children with LS. It accelerated linear
      growth rates to 8-9 cm in the first year of treatment, compared with 10-12
      cm/year during GH treatment of IGHD. The growth rate in following years was 5-6.5
      cm/year. CONCLUSION: IGF-1 is an important growth hormone, mediating the protein
      anabolic and linear growth promoting effect of pituitary GH. It has a GH
      independent growth stimulating effect, which with respect to cartilage cells is
      possibly optimised by the synergistic action with GH.

PMID- 11577174
TI  - The Twisted gastrulation family of proteins, together with the IGFBP and CCN
      families, comprise the TIC superfamily of cysteine rich secreted factors.
AB  - AIMS: To analyse the similarities between the Twisted gastrulation (TSG) proteins
      known to date; in addition, to determine phylogenetic relations among the TSG
      proteins, and between the TSGs and other protein families--the CCN (for example,
      CCN2 (CTGF), CCN1 (CYR61), and CCN3 (NOV)) and IGFBP (insulin-like growth factor
      binding protein) families. METHODS: TBLASTN and FASTA3 were used to identify new
      tsg genes and relatives of the TSG family. The sequences were aligned with
      ClustalW. The predictions of sites for signal peptide cleavage, post
      translational modifications, and putative protein domains were carried out with
      software available at various databases. Unrooted phylogenetic trees were
      calculated using the UPGMA method. RESULTS: Several tsg genes from vertebrates
      and invertebrates were compared. Alignment of protein sequences revealed a highly
      conserved family of TSG proteins present in both vertebrates and invertebrates,
      whereas the slightly less well conserved IGFBP and CCN proteins are apparently
      present only in vertebrates. The TSG proteins display strong homology among
      themselves and they are composed of a putative signal peptide at the N-terminus
      followed by a cysteine rich (CR) region, a conserved domain devoid of cysteines,
      a variable midregion, and a C-terminal CR region. The most striking similarity
      between the TSGs and the IGFBP and CCN proteins occurs in the N-terminal
      conserved cysteine rich domain and the characteristic 5' cysteine rich domain(s),
      spacer region, and 3' cysteine rich domain structure. CONCLUSION: The family of
      highly conserved TSG proteins, together with the IGFBP and CCN families,
      constitute an emerging multigene superfamily of secreted cysteine rich factors.
      The TSG branch of the superfamily appears to pre-date the others because it is
      present in all species examined, whereas the CCN and IGFBP genes are found only
      in vertebrates.

PMID- 11577175
TI  - Differentially expressed genes in association with in vitro invasiveness of human
      epithelioid sarcoma.
AB  - AIMS: Differential display reverse transcription polymerase chain reaction (RT
      PCR) was performed to identify genes associated with the invasive potential of
      human epithelioid sarcoma. METHODS: Two different clonal subpopulations, GRU-1A
      and GRU-1B, derived from the same human epithelioid sarcoma cell line GRU-1 and
      known to differ greatly in their invasive potential were compared by means of
      mRNA fingerprinting. RESULTS: Using a set of 10 arbitrary upstream primers and
      nine anchored oligo-dT primers, 22 candidate gene fragments were identified;
      differential expression was confirmed in four of these fragments by northern blot
      analysis. At the mRNA level, apoferritin light chain was predominantly expressed
      by the highly invasive cell line GRU-1A. In contrast, the mitochondrial gene M1,
      encoding cytochrome c oxidase I, and the TI-227H gene were expressed more
      strongly by the low invasive cell line GRU-1B. Furthermore, a novel gene fragment
      was identified and cloned that was preferentially expressed in the low invasive
      cell line GRU-1B, and therefore might have an inhibitory role in invasion.
      Consequently, this gene fragment was designated as expressed in low invasive
      sarcoma cells (ELISC-1). CONCLUSIONS: A novel gene fragment (ELISC-1) and three
      known genes were identified as potential regulators of tumour invasiveness.
      Cloning of the entire sequence of ELISC-1 and subsequent investigations are
      required to establish its biological role.

PMID- 11577176
TI  - Expression of a human polyomavirus oncoprotein and tumour suppressor proteins in
      medulloblastomas.
AB  - AIMS: Although the aetiology of medulloblastoma remains elusive, several lines of
      evidence suggest an association with the human neurotropic polyomavirus JC and
      its oncoprotein T antigen. The tumour forming properties of JC virus T antigen
      are the result, at least in part, of its ability to bind and inactivate tumour
      suppressor/cell cycle regulatory proteins, such as p53 and the retinoblastoma
      family of proteins. METHODS: To examine potential relations between these
      factors, immunohistochemistry was used to determine associations between the T
      antigen and the expression of p53 and the retinoblastoma proteins pRb, p107, and
      Rb2/p130 in eight medulloblastomas. RESULTS: Only the three medulloblastomas with
      T antigen expression also showed nuclear positivity with antibodies to p53.
      Although immunohistochemistry detected nuclear labelling for pRb in five of the
      cases, the three that were positive for T antigen showed the highest pRb
      labelling. The retinoblastoma related proteins p107 and Rb2/p130 were also
      immunopositive in most T antigen positive medulloblastomas. Double label
      immunohistochemistry also demonstrated p53 and pRb positivity in the same cells
      that were T antigen positive. CONCLUSIONS: These correlations suggest that
      associations between T antigen and p53 and/or T antigen and pRb occur in some of
      these tumours. These data provide indirect evidence that JC virus, acting through
      T antigen, might be involved in the formation and progression of medulloblastoma.

PMID- 11577177
TI  - Steroidal regulation of connective tissue growth factor (CCN2; CTGF) synthesis in
      the mouse uterus.
AB  - AIMS: To determine mechanisms regulating the production of connective tissue
      growth factor (CCN2; CTGF) and transforming growth factor beta1 (TGF-beta1) in
      the mouse uterus. METHODS: In situ hybridisation and immunohistochemistry were
      used to localise CCN2 (CTGF) and TGF-beta1 in uteri from sexually mature female
      mice that had either been (1) mated with sterile males to induce pseudopregnancy
      or (2) ovariectomised (OVX) and administered estradiol-17beta (E2) or
      progesterone (P4), either alone or in combination. Uteri collected on days 0.5,
      1.5, 2.5, 3.5, 4.5, or 5.5 of pseudopregnancy or at one, three, six, 12, or 24
      hours after steroid administration were fixed, sectioned, and incubated with
      specific riboprobes or antibodies to permit detection and localisation of mRNA or
      protein for CTGF and TGF-beta1. RESULTS: On days 0.5-2.5 of pseudopregnancy, CCN2
      (CTGF) and TGF-beta1 were principally colocalised to uterine epithelial cells,
      with much smaller amounts in the stroma. On days 3.5-4.5, there was a reduction
      of CCN2 (CTGF) and TGF-beta1 in the epithelium but an increase in stromal and
      endothelial cells, corresponding to a period of extracellular matrix remodelling
      and neovascularisation within the endometrium. In OVX mice, epithelial cells were
      weakly positive for both CCN2 (CTGF) and TGF-beta1 in the absence of steroid
      hormones. Epithelial CTGF mRNA production were strongly but transiently
      stimulated in OVX mice cells by E2. These effects were antagonised by P4, which
      itself transiently stimulated epithelial CCN2 (CTGF) production, although less
      robustly than E2. CTGF and TGF-beta1 protein amounts were high in epithelial
      cells throughout steroid treatment and were increased in the stroma, where they
      were relatively long lived. Stromal CCN2 (CTGF) and TGF-beta1 were lower after co
      administration of E2 and P4 than in response to each hormone individually.
      Although ccn2 (ctgf) is a TGF-beta1 inducible gene in other systems, and both
      growth factors were often co-localised in uterine tissues in these studies,
      several treatment regimens resulted in high amounts of TGF-beta1 protein in
      stromal cells without the concomitant production of ccn2 (ctgf) mRNA.
      CONCLUSIONS: Maternal factors are principal cues for CCN2 (CTGF) and TGF-beta1
      production in the uterus because (1) their expression during pseudopregnancy is
      comparable to that seen in pregnancy and (2) they are regulated by ovarian
      steroids. TGF-beta dependent and independent mechanisms of ccn2 (ctgf) gene
      transcription exist in the uterus that are variably regulated by steroid
      hormones. Collectively, the data support a role for CCN2 (CTGF) in mediating the
      effects of steroid hormones and TGF-beta on endometrial function.

PMID- 11577178
TI  - Cell cycle dependent DNA break increase in ataxia telangiectasia lymphoblasts
      after radiation exposure.
AB  - The most striking feature of ataxia telangiectasia (AT) cells is their profound
      sensitivity to ionising radiation. A deficiency in the rejoining of radiation
      induced DNA breaks has been suggested to be responsible for AT radiosensitivity;
      however, the existing literature is controversial. A subpopulation, which is
      present in irradiated AT lymphoblasts, but rarely in controls, has been reported
      previously. The cells that make up this subpopulation harbour highly fragmented
      DNA and are responsible for the overall increase in DNA breaks soon after
      irradiation in AT lymphoblasts. This study examines the influence of the cell
      cycle on the highly damaged subpopulation. The frequency of highly damaged cells
      was highest when AT lymphoblasts were irradiated during the G2/M phase. In
      contrast, AT lymphoblasts irradiated during the G0/G1 phase displayed a frequency
      similar to control cells. Thus, only G2/M and to some extent S phase cells
      contribute to an increased DNA break number in AT lymphoblasts early after
      irradiation. These findings might explain several inconsistencies reported in the
      literature.

PMID- 11577179
TI  - PCR amplification introduces errors into mononucleotide and dinucleotide repeat
      sequences.
AB  - The polymerase chain reaction (PCR) is used universally for accurate exponential
      amplification of DNA. We describe a high error rate at mononucleotide and
      dinucleotide repeat sequence motifs. Subcloning of PCR products allowed sequence
      analysis of individual DNA molecules from the product pool and revealed that: (1)
      monothymidine repeats longer than 11 bp are amplified with decreasing accuracy,
      (2) repeats generally contract during PCR because of the loss of repeat units,
      (3) Taq and proofreading polymerase Pfu generate similar errors at mononucleotide
      and dinucleotide repeats, and (4) unlike the parent PCR product pool, individual
      clones containing a single repeat length produce no "shadow bands". These data
      demonstrate that routine PCR amplification alters mononucleotide and dinucleotide
      repeat lengths. Such sequences are common components of genetic markers, disease
      genes, and intronic splicing motifs, and the amplification errors described here
      can be mistaken for polymorphisms or mutations.

PMID- 11577180
TI  - Concomitant progressive multifocal leucoencephalopathy and primary central
      nervous system lymphoma expressing JC virus oncogenic protein, large T antigen.
AB  - This report describes the concomitant occurrence of the JC virus (JCV) induced
      demyelinating disease progressive multifocal leucoencephalopathy (PML) and a
      primary central nervous system lymphoma (PCNS-L) in a patient with AIDS.
      Postmortem neuropathological examination revealed characteristic features of PML
      including multiple lesions of demyelination, enlarged oligodendrocytes with
      hyperchromatic nuclei (many containing eosinophilic intranuclear inclusions), and
      enlarged astrocytes with bizarre hyperchromatic nuclei. Immunohistochemical
      analysis demonstrated the expression of the JCV capsid protein VP-1 in the nuclei
      of infected oligodendrocytes and astrocytes. The PCNS-L lesion located in the
      basal ganglia was highly cellular, distributed perivascularly, and consisted of
      large atypical plasmacytoid lymphocytes. Immunohistochemical examination of this
      neoplasm identified it to be of B cell origin. Moreover, expression of the JCV
      oncogenic protein, T antigen, was detected in the nuclei of the neoplastic
      lymphocytes. This study provides the first evidence for a possible association
      between JCV and PCNS-L.

PMID- 11577181
TI  - Technical advance: an automated device for cryofixation of specimens of electron
      microscopy using liquid helium.
AB  - Metal-contact rapid freezing using liquid helium is theoretically the best method
      for preserving the fine structure of living cells with high temporal resolution
      in preparation of tissue samples for electron microscopy. However, this method is
      not commonly used, because of its technical difficulty and low reproducibility.
      We have designed and constructed an automatic device which allows simple, rapid
      and reproducible preparation of high-quality electron microscopic specimens by
      the non-specialist. We assessed the quality of cryofixation in samples prepared
      using this device by examining the preservation of cellular ultrastructure in
      relation to distance from the freezing block, and found that the region within 10
      microm of the metal-contact plane was fixed with the highest quality. We applied
      this device, in combination with freeze-substitution methods and
      immunocytochemical techniques, to two phenomena involving rapid movement of
      subcellular components: (1) active movement of subcellular structures in the
      papillar cells of stigma and (2) light-induced rapid subcellular translocation of
      phytochrome A. Considering the importance of understanding subcellular processes
      of living cells for molecular and cell biology, this device will be a useful tool
      for diverse biological applications in the near future.

PMID- 11577182
TI  - A proteinase-storing body that prepares for cell death or stresses in the
      epidermal cells of Arabidopsis.
AB  - Plants degrade cellular materials during senescence and under various stresses.
      We report that the precursors of two stress-inducible cysteine proteinases, RD21
      and a vacuolar processing enzyme (VPE), are specifically accumulated in
      approximately 0.5 microm diameter x approximately 5 microm long bodies in
      Arabidopsis thaliana. Such bodies have previously been observed in Arabidopsis
      but their function was not known. They are surrounded with ribosomes and thus are
      assumed to be directly derived from the endoplasmic reticulum (ER). Therefore, we
      propose to call them the ER bodies. The ER bodies are observed specifically in
      the epidermal cells of healthy seedlings. These cells are easily wounded and
      stressed by the external environment. When the seedlings are stressed with a
      concentrated salt solution, leading to death of the epidermal cells, the ER
      bodies start to fuse with each other and with the vacuoles, thereby mediating the
      delivery of the precursors directly to the vacuoles. This regulated, direct
      pathway differs from the usual case in which proteinases are transported
      constitutively from the ER to the Golgi complex and then to vacuoles, with
      intervention of vesicle-transport machinery, such as a vacuolar-sorting receptor
      or a syntaxin of the SNARE family. Thus, the ER bodies appear to be a novel
      proteinase-storing system that assists in cell death under stressed conditions.

PMID- 11577183
TI  - A putative two pore channel AtTPC1 mediates Ca(2+) flux in Arabidopsis leaf
      cells.
AB  - The gene encoding voltage-gated channel with high affinity for Ca(2+) permeation
      has not been cloned from plants. In the present study, we isolated a full-length
      cDNA encoding a putative Ca(2+ )channel (AtTPC1) from Arabidopsis. AtTPC1 has two
      conserved homologous domains, both of which contain six transmembrane segments
      (S1-S6) and a pore loop (P) between S5 and S6 in each domain, and has the highest
      homology with the two pore channel TPC1 recently cloned from rat. The overall
      structure is similar to the half of the general structure of alpha-subunits of
      voltage-activated Ca(2+) channels from animals. AtTPC1 rescued the Ca(2+) uptake
      activity of a yeast mutant cch1. Sucrose-induced luminescence, which reflects a
      cytosolic free Ca(2+) increase in aequorin-expressing Arabidopsis leaves, was
      enhanced by overexpression of AtTPC1 and suppressed by antisense expression of
      it. Sucrose-H(+) symporters AtSUC1 and 2, which depolarize membrane potential of
      cells receiving sucrose, also depressed a Ca(2+) increase by their antisense
      expression. These results suggest that AtTPC1 mediates a voltage-activated Ca(2+
      )influx in Arabidopsis leaf cells.

PMID- 11577184
TI  - Water-soluble chlorophyll protein in Brassicaceae plants is a stress-induced
      chlorophyll-binding protein.
AB  - Two kinds of water-soluble chlorophyll (Chl) proteins (WSCPs) have been found,
      e.g., a WSCP from Chenopodium, Atriplex, Polygonum, and Amaranthus species (class
      I) and that from Brassica, Raphanus, and Lepidium species (class II). Classes I
      and II WSCPs differ mainly in their photoconvertiblity. Class I WSCPs show a
      light-induced absorption change, whereas Class II WSCPs do not. The molecular and
      functional properties of Class I WSCP are largely uncertain. On the other hand,
      recent studies on the adaptation of plants to osmotic stress revealed the
      participation of drought-stress induced proteins with molecular masses of 20-22
      kDa possessing a sequence similarity with class II WSCPs. This mini review
      focuses on the molecular signature of class II WSCPs. The physiological function
      of class II WSCPs has not been clarified either, but, their water-solubility, low
      Chl content, and stress-inducibility suggested little contribution to
      photosynthesis. Several molecular properties predicting its physiological role
      are as follows. The WSCP tetramer, may have only one or no Chl molecules in each
      subunit. All WSCPs possess a motif for Kunitz-type proteinase inhibitor family in
      their sequence. WSCP is induced by drought- and heat-stresses suggesting its
      protective role during stress conditions. Monomeric recombinant apo-WSCP is able
      to remove Chls from the thylakoid membrane in aqueous solution and form into a
      tetramer. Brassica-WSCP contains a signal sequence targeted to endoplasmic
      reticulum. The highly conserved, C-terminal region is missing in the mature WSCP.
      Possible functions of class II WSCPs in plant tissues are discussed.

PMID- 11577185
TI  - Mastoparan alters subcellular distribution of profilin and remodels F-actin
      cytoskeleton in cells of maize root apices.
AB  - Indirect immunofluorescence localization of profilin in cells of maize root
      apices revealed that this abundant protein was present both in the cytoplasm and
      within nuclei. Nucleo-cytoplasmic partitioning of profilin exhibits tissue
      specific and developmental features. Mastoparan-mediated activation of
      heterotrimeric G-proteins, presumably through triggering a phosphoinositide
      signaling pathway based on phosphatidylinositol-4,5-bisphosphate (PIP(2)),
      induced relocalization of profilin from nuclei into the cytoplasm of root apex
      cells. In contrast, PIP(2) accumulated within nuclei of mastoparan-treated root
      cells. Intriguingly, cytoplasmic accumulation of profilin was associated with
      remodeling of F-actin arrays in root apex cells. Specifically, dense F-actin
      networks were dismantled and distinct actin patches became associated with the
      periphery of small vacuoles. On the other hand, disruption of F-actin with the G
      actin sequestering agent latrunculin B does not affect the subcellular
      distribution of profilin or PIP(2). These data suggest that nuclear profilin can
      mediate a stimulus-response action on the actin cytoskeleton which is somehow
      linked to a phosphoinositide-signaling cascade.

PMID- 11577186
TI  - Possible involvement of auxin-induced ethylene in an apoptotic cell death during
      temperature-sensitive lethality expressed by hybrid between Nicotiana glutinosa
      and N. repanda.
AB  - Interspecific hybrids of Nicotiana glutinosa L. x N. repanda Willd. express
      temperature-sensitive lethality induced by apoptotic cell death. Hybrid seedlings
      cultured at 28 degrees C began to exhibit lethal symptoms during early growth
      stages, and then they showed a high level of endogenous auxin compared with those
      of parental seedlings. Meanwhile, the level of auxin in hybrid seedlings cultured
      at 32 degrees C, which is a condition suppressing the lethality of this cross
      combination, was equal to or lower than those of parental seedlings.
      Administration of 2,3,5-triiodobenzoic acid (TIBA) as an auxin transport
      inhibitor into the hybrid seedlings suppressed lethal symptoms and had a life
      extending effect. Additionally, TIBA has an effect to suppress DNA fragmentation,
      which is one of characteristics of apoptosis and has been detected in the hybrid
      seedlings expressing the lethality. Administration of aminooxyacetic acid (AOA)
      as an ethylene synthesis inhibitor, which could inhibit ethylene production, also
      showed the same effects as TIBA for the lethality. From these results, we
      suggested that auxin and ethylene were involved in an apoptotic cell death during
      the lethality, and the abnormal increase of endogenous auxin may lead to the
      ethylene production in hybrid seedlings during early growth stages.

PMID- 11577187
TI  - The distribution of protochlorophyllide and chlorophyll within seedlings of the
      lip1 mutant of Pea.
AB  - The distribution of protochlorophyllide (Pchlide) and NADPH-Pchlide
      oxidoreductase (POR) was characterized in the epicotyls and roots of wild-type
      pea (Pisum sativum L. cv. Alaska) and lip1, a mutant with light-independent
      photomorphogenesis caused by a mutation in the COP1 locus. The upper part of the
      dark-grown lip1 mutant epicotyls had a high Pchlide content that decreased
      downward the organ. The elevated Pchlide level in lip1 seedlings was a result of
      the differentiation of more proplastids into Pchlide-containing plastids. The
      cortex cells in the lip1 epicotyl were filled with such plastids in contrast to
      the cortex cells of wild-type seedlings. The mutant also developed Pchlide
      containing plastids in the roots, indicating the suppressing effect of the COP1
      locus on development of plastids in the corresponding tissues in dark-grown wild
      type plants. The distribution of Pchlide-containing plastids in dark-grown lip1
      mutant stem and root was similar to the distribution of chloroplasts in
      irradiated wild-type plants. Both wild-type and lip1 epicotyls contained mostly
      short wavelength Pchlide fluorescing at 631 nm with only a small shoulder at 654
      nm, which was transformed to a minute amount of chlorophyllide (Chlide) by flash
      irradiation. In contrast, with continuous irradiation a considerable amount of
      Chlide was formed especially in the lip1 epicotyls. Immunoblots indicated the
      presence of POR, as a 36 kDa band, in epicotyls of both dark-grown wild-type and
      lip1 mutant seedlings. However, lip1 stem tissue had a higher content of POR than
      the wild-type pea. The high content of POR was unexpected as lip1 lacked both the
      654 nm fluorescing Pchlide form and the regular PLBs. In light, a significant
      amount of chlorophyll was formed also in the roots of the lip1 seedlings.

PMID- 11577188
TI  - Subcellular localization and targeting of glucocorticoid receptor protein fusions
      expressed in transgenic Arabidopsis thaliana.
AB  - An animal system of inducible activation of protein fusions with the binding
      domain of glucocorticoid receptor (BDGR) was tested in Arabidopsis thaliana by
      monitoring dexamethasone (DEX)-induced nuclear targeting of reporter constructs.
      Two constructs containing green fluorescent protein (GFP), human homeobox protein
      Hanf-1 and Xenopus laevis BDGR were used, GFP/Hanf-1/BDGR and GFP/BDGR. The
      control construct contained GFP alone. In the absence of DEX both fusion proteins
      were uniformly distributed in the cytoplasm of root cells, but showed strong
      association with plastids in plant aerial parts. DEX treatment of roots prompted
      a strong and reversible nuclear accumulation of GFP/Hanf-1/BDGR, but not
      GFP/BDGR. Thus, in roots, the specific nuclear translocation of GFP/Hanf-1/BDGR
      was driven by Hanf-1 and tightly regulated by BDGR. However, in plant aerial
      parts treated with DEX, nuclear translocation of GFP/Hanf-1/BDGR was observed
      only in a few cases, and most part of the fusion protein was incorrectly and
      irreversibly targeted to plastids. Protease X digestion of isolated chloroplasts
      showed that BDGR fusion proteins were translocated into the chloroplast envelope
      and bound to envelope membranes, probably due to association with the chloroplast
      import apparatus. Thus, for efficient use of the glucocorticoid-inducible system
      in plants, it will be necessary to modify BDGR structure to prevent incorrect
      targeting of fusion proteins.

PMID- 11577189
TI  - Distribution of yieldin, a regulatory protein of the cell wall yield threshold,
      in etiolated cowpea seedlings.
AB  - We examined the distribution and the immunohistochemical localization of yieldin
      in etiolated cowpea seedlings with an anti-yieldin antibody. An immunoblotting
      analysis revealed that the yieldin was located in the aerial organs (plumule,
      epicotyl and hypocotyl) but not in the roots. The intensity of the yieldin signal
      in the hypocotyls was highest in the apical pre-elongation region (the hook
      region) and decreased toward the elongated mature base indicating that the
      yieldin disappeared with the ceasing of cell elongation. Tissue-print
      immunoblotting analysis using hypocotyls in different germination stages supports
      this view because the apical yieldin-rich regions, just beneath the cotyledonary
      node (the hook and rapidly elongating regions), acropetally migrated together
      with hypocotyl elongation. Immunohistochemical microscopy demonstrated that
      yieldin was localized in the cell walls of the cortex and epidermis of the germ
      axes. The present results are consistent with the view that yieldin participates
      in the regulation of cell wall yielding during elongation growth.

PMID- 11577190
TI  - Progress of lignification mediated by intercellular transportation of monolignols
      during tracheary element differentiation of isolated Zinnia mesophyll cells.
AB  - Tracheary element (TE) differentiation is a typical example of programmed cell
      death (PCD) in higher plants, and maturation of TEs is completed by degradation
      of all cell contents. However, lignification of TEs progresses even after PCD. We
      investigated how and whence monolignols are supplied to TEs which have undergone
      PCD during differentiation of isolated Zinnia mesophyll cells into TEs. Higher
      densities of cell culture induced greater lignification of TEs. Whereas the
      continuous exchanging of culture medium suppressed lignification of TEs, further
      addition of coniferyl alcohol into the exchanging medium reduced the suppression
      of lignification. Analysis of the culture medium by HPLC and GC-MS showed that
      coniferyl alcohol, coniferaldehyde, and sinapyl alcohol accumulated in TE
      inductive culture. The concentration of coniferyl alcohol peaked at the beginning
      of secondary wall thickening, decreased rapidly during secondary wall thickening,
      then increased again. These results indicated that lignification on TEs
      progresses by supply of monolignols from not only TEs themselves but also
      surrounding xylem parenchyma-like cells through medium in vitro.

PMID- 11577191
TI  - Isolation and purification of tyrosine hydroxylase from callus cultures of
      Portulaca grandiflora.
AB  - Tyrosine hydroxylase was separated from polyphenol oxidase activity and was
      highly purified from betacyanin producing callus cultures of Portulaca
      grandiflora. The purified enzyme catalyzed the formation of DOPA (L-3,4
      dihydroxyphenylalanine) from tyrosine and required the pterin compounds (6-methyl
      5,6,7,8-tetrahydropterin; 5,6,7,8-tetrahydrobiopterin; 6,7-dimethyl-5,6,7,8
      tetrahydropterin) as coenzyme. The K(m) values for tyrosine and 6-methyl-5,6,7,8
      tetrahydropterin were 0.5 mM and 0.15 mM, respectively. This enzyme was activated
      by Fe(2+) and Mn(2+), and inhibited by metal chelating agents.

PMID- 11577192
TI  - An Arabidopsis SNF1-related protein kinase, AtSR1, interacts with a calcium
      binding protein, AtCBL2, of which transcripts respond to light.
AB  - AtSR1 is a protein kinase of Arabidopsis thaliana, which belongs to the SNF1
      related protein kinase subfamily 3. We previously showed accumulation of its
      transcripts to be responsive to light. In this study, we examined the interaction
      between AtSR1 and six calcineurin B like proteins of Arabidopsis and found that
      AtSR1 prominently interacts with one of them, AtCBL2, by yeast two-hybrid assay.
      Interaction between AtSR1 and AtCBL2 could also be directly confirmed in vitro by
      pull down assay. RNA blot and reverse transcription-polymerase chain reaction
      analyses showed that transcripts of AtCBL2, and also of AtCBL1, another CBL,
      increased upon illumination of leaves. The physiological meaning of the
      interaction of AtSR1and AtCBL2 is not clear, but they presumably function in
      signal transduction of light.

PMID- 11577194
TI  - A phycocyanin-deficient mutant of synechocystis PCC 6714 with a single-base
      substitution upstream of the cpc operon.
AB  - The structure and expression of the cpc operon encoding phycocyanin subunits and
      linker polypeptides in a phycocyanin-deficient mutant (PD-1) and the wild-type of
      Synechocystis PCC 6714 were analyzed. The results of sequence and Northern blot
      analyses of the wild type indicate that the cpc operon consists of cpcB, cpcA,
      cpcC1, cpcC2 and cpcD, in that order. The levels of the transcripts in PD-1 were
      one-tenth to one-sixth as high as those in the wild type. In the PD-1 genome, a
      single-base substitution of C for T has occurred at base 259 upstream of the
      translational initiation codon of cpcB (at three bases downstream of the putative
      -10 region). To evaluate the in vivo transcription activities of these promoters
      in a cyanobacterium, we constructed vectors for the transformation of
      Synechococcus PCC7942, pANY1 and pANY2, which contain the upstream region of cpcB
      of the wild type (pANY1) or PD-1 (pANY2) and the promoter-less luxAB fusion. The
      bioluminescence of the transformants with pANY2 was one-tenth to one-sixth as
      high as that with pANY1. The coincidence of the results of Northern analysis and
      the promoter assay shows that the phycocyanin deficiency of PD-1 is due to the
      single-base substitution in the upstream region of the cpc operon.

PMID- 11577193
TI  - The Purple leaf (Pl) locus of rice: the Pl(w) allele has a complex organization
      and includes two genes encoding basic helix-loop-helix proteins involved in
      anthocyanin biosynthesis.
AB  - The Purple leaf (Pl) locus of rice (Oryza sativa L.) affects regulation of
      anthocyanin biosynthesis in various plant tissues. The tissue-specific patterns
      of anthocyanin pigmentation, together with the syntenic relationship, indicate
      that the rice Pl locus may play a role in the anthocyanin pathway similar to the
      maize R/B loci. We isolated two cDNAs showing significant identity to the basic
      helix-loop-helix (bHLH) proteins found in the maize R gene family. OSB1 appeared
      to be allelic to the previously isolated R homologue, Ra1, but showed a striking
      difference at the C-terminus because of a 2-bp deletion. Characterization of the
      corresponding genomic region revealed that the sequence identical to a 5'-portion
      of OSB2 existed approximately 10-kb downstream of the OSB1 coding region. OSB2
      lacks a conserved C-terminal domain. Restriction fragment length polymorphism
      analyses using an F(2) population indicate that both genes co-segregate with the
      purple leaf phenotype. A transient complementation assay showed that the
      anthocyanin pathway is inducible by OSB1 or OSB2. These results suggest that the
      Pl(w) allele may be complex and composed of at least two genes encoding bHLH
      proteins.

PMID- 11577195
TI  - Cold acclimation can induce microtubular cold stability in a manner distinct from
      abscisic acid.
AB  - The response of cortical microtubules to low temperature was investigated for the
      Chinese winter wheat (Triticum aestivum L.) cultivar Jing Nong 934. Microtubules
      in the cortex of the root elongation zone disassembled rapidly in response to a
      cold shock of -7 degrees C and reassembled upon rewarming to 25 degrees C. The
      microtubules acquired resistance against this cold shock in response to cold
      acclimation in chilling, but non-freezing, temperature or after a treatment with
      abscisic acid (ABA). Cold acclimation and ABA differed with respect to the
      appearance of microtubules: fine, transverse strands were observed after cold
      acclimation, whereas ABA produced steeply oblique microtubule bundles. The
      findings are discussed in terms of an ABA-independent pathway for acquired cold
      stability of microtubules.

PMID- 11577196
TI  - Brassinazole, an inhibitor of brassinosteroid biosynthesis, inhibits development
      of secondary xylem in cress plants (Lepidium sativum).
AB  - Brassinazole (Brz) is a specific brassinosteroid biosynthesis inhibitor. Cress
      plants (Lepidium sativum) grown in medium containing Brz exhibited a slight
      predominance of phloem differentiation at the expense of xylem differentiation
      and remarkable inhibition of the development of secondary xylem. This result
      indicates that brassinosteroids function in xylem development in vivo.

PMID- 11577197
TI  - Oxidative stress activates ATMPK6, an Arabidopsis homologue of MAP kinase.
AB  - Mitogen-activated protein kinase (MAPK) cascades function in biotic and abiotic
      stress responses in plants. We analysed effect of oxidative stress on the
      activation of ATMPK6, an Arabidopsis thaliana MAPK, in Arabidopsis T87 cultured
      cells and rosette leaves using anti-ATMPK6 specific antibody. ATMPK6 in T87 cells
      was strongly activated by reactive oxygen species (ROS) such as H(2)O(2) and
      KO(2). In leaves, ATMPK6 was activated by paraquat and 3-amino-1,2,4-triazole (a
      catalase inhibitor). These results indicate that ATMPK6 is one of the candidates
      for signal mediators in response to abiotic or biotic sources for ROS in
      Arabidopsis.

PMID- 11577198
TI  - The Arabidopsis AHK4 histidine kinase is a cytokinin-binding receptor that
      transduces cytokinin signals across the membrane.
AB  - Common histidine-to-aspartate (His-->Asp) phosphorelay is a paradigm of signal
      transduction in both prokaryotes and eukaryotes for the propagation of certain
      environmental stimuli, in which histidine (His)-kinases play central roles as
      sensors for environmental signals. For the higher plant, Arabidopsis thaliana, it
      was recently suggested that the His-kinase (AHK4 / CRE1 / WOL) is a sensor for
      cytokinins, which are a class of plant hormones important for the regulation of
      cell division and differentiation. Interestingly, AHK4 is capable of functioning
      as a cytokinin sensor in the eubacterium, Escherichia coli (Suzuki et al. 2001,
      Plant Cell Physiol. 42: 107). Here we further show that AHK4 is a primary
      receptor that directly binds a variety of natural and synthetic cytokinins (e.g.
      not only N(6)-substituted aminopurines such as isopentenyl-adenine, trans-zeatin,
      benzyl-adenine, but also diphenylurea derivatives such as thidiazuron), in a
      highly specific manner (K(d) = 4.55+/-0.48x10(-9) M). AHK4 has a presumed
      extracellular domain, within which a single amino acid substitution (Thr-301 to
      Ile) was shown to result in loss of its ability to bind cytokinins. This
      particular mutation corresponds to the previously reported wol allele (wooden
      leg) that causes a striking phenotype defective in vascular morphogenesis.
      Collectively, evidence is presented that AHK4 and its homologues (AHK3 and
      possibly AHK2) are receptor kinases that can transduce cytokinin signals across
      the plasma membrane of A. thaliana.

PMID- 11577199
TI  - Liver organogenesis promoted by endothelial cells prior to vascular function.
AB  - The embryonic role of endothelial cells and nascent vessels in promoting
      organogenesis, prior to vascular function, is unclear. We find that early
      endothelial cells in mouse embryos surround newly specified hepatic endoderm and
      delimit the mesenchymal domain into which the liver bud grows. In flk-1 mutant
      embryos, which lack endothelial cells, hepatic specification occurs, but liver
      morphogenesis fails prior to mesenchyme invasion. We developed an embryo tissue
      explant system that permits liver bud vasculogenesis and show that in the absence
      of endothelial cells, or when the latter are inhibited, there is a selective
      defect in hepatic outgrowth. We conclude that vasculogenic endothelial cells and
      nascent vessels are critical for the earliest stages of organogenesis, prior to
      blood vessel function.

PMID- 11577200
TI  - Induction of pancreatic differentiation by signals from blood vessels.
AB  - Blood vessels supply developing organs with metabolic sustenance. Here, we
      demonstrate a role for blood vessels as a source of developmental signals during
      pancreatic organogenesis. In vitro experiments with embryonic mouse tissues
      demonstrate that blood vessel endothelium induces insulin expression in isolated
      endoderm. Removal of the dorsal aorta in Xenopus laevis embryos results in the
      failure of insulin expression in vivo. Furthermore, using transgenic mice, we
      show that ectopic vascularization in the posterior foregut leads to ectopic
      insulin expression and islet hyperplasia. These results indicate that vessels not
      only provide metabolic sustenance, but also provide inductive signals for organ
      development.

PMID- 11577201
TI  - Observation of charge transport by negatively charged excitons.
AB  - We report transport of electron-hole complexes in semiconductor quantum wells
      under applied electric fields. Negatively charged excitons (X-), created by laser
      excitation of a high electron mobility transistor, are observed to drift upon
      applying a voltage between the source and drain. In contrast, neutral excitons do
      not drift under similar conditions. The X- mobility is found to be as high as 6.5
      x 10(4) cm2 V-1 s-1. The results demonstrate that X- exists as a free particle in
      the best-quality samples and suggest that light emission from opto-electronic
      devices can be manipulated through exciton drift under applied electric fields.

PMID- 11577203
TI  - An extraterrestrial impact at the Permian-Triassic boundary?

PMID- 11577202
TI  - Development. Endothelium--chicken soup for the endoderm.
AB  - Endothelial cells in blood vessels are known to be important during the later
      stages of organ development in the embryo. However, their involvement at the
      induction stage of organ formation has not been previously documented. As Bahary
      and Zon explain in their Perspective, new work demonstrates that endothelial
      cells secrete factors early in development that induce embryonic endoderm to
      become liver or pancreas (Matsumoto et al., Lammert et al.).

PMID- 11577205
TI  - Research funding. White House asks community to oppose earmark projects.

PMID- 11577204
TI  - Biological security in a changed world.

PMID- 11577207
TI  - Planetary science. New visitors set for lunar voyage.

PMID- 11577206
TI  - Developmental biology. Organs await blood vessels' go signal.

PMID- 11577208
TI  - Stem cell research. Reports give green light in Australia, Israel.
AB  - BERLIN AND MELBOURNE--After 2 years of deliberation, an Australian government
      committee has endorsed legislation that would allow both human embryonic stem
      cell research and the derivation of ES cells from unwanted embryos created during
      fertility treatments. And in Israel, another country at the forefront of work on
      ES cells, a national bioethics committee has approved both the derivation of ES
      cells and research into therapeutic cloning.

PMID- 11577209
TI  - Condensed matter. Quantum condensate gets a fresh squeeze.
AB  - Cooled to a few billionths of a degree above absolute zero, atoms in a Bose
      Einstein condensate represent an extreme state of matter. But physicists have now
      subjected the atoms in condensates to even more outrageous ordeals, squeezing
      them into one-dimensional lines and two-dimensional planes. The experiments,
      reported in the 24 September Physical Review Letters, open the door to
      investigating a new regime of physics in which the rules are easier to
      understand.

PMID- 11577210
TI  - Paleoanthropology. Tools show humans reached Asia early.

PMID- 11577212
TI  - Magnetospheric physics. Magnetic storms have two drivers, not one.

PMID- 11577211
TI  - French science. Budget backs university research, job creation.

PMID- 11577213
TI  - Malaria research. Two new steps toward a 'better mosquito'.

PMID- 11577214
TI  - Paleontology. Unhatched eggs help dinos get a head.

PMID- 11577215
TI  - Clinical research. India acts on flawed cancer drug trials.

PMID- 11577216
TI  - Forensic anthropology. For Ice Man, the band plays on.

PMID- 11577217
TI  - Swedish bioscience. Karolinska Inc.

PMID- 11577218
TI  - Swedish bioscience. Working Sweden's population gold mine.

PMID- 11577219
TI  - Evolution. Evolutionary pulse found, but complexity as well.

PMID- 11577220
TI  - Ecology. Cave biologists unearth buried treasure.

PMID- 11577221
TI  - Energy. Plutonium and reprocessing of spent nuclear fuel.

PMID- 11577222
TI  - Paleoecology. Measuring past biodiversity.

PMID- 11577223
TI  - Cell biology. Life without caveolae.

PMID- 11577224
TI  - Neuroscience. The face of controversy.

PMID- 11577226
TI  - Astronomy. A stellar merry-go-round.

PMID- 11577225
TI  - Neurobiology. Dopamine's reversal of fortune.

PMID- 11577227
TI  - Superconductivity. The race to beat the cuprates.

PMID- 11577228
TI  - Neutral macroecology.
AB  - The central themes of community ecology-distribution, abundance, and diversity
      display strongly marked and very general patterns. These include the log-normal
      distribution of abundance, the relation between range and abundance, the species
      area law, and the turnover of species composition. Each pattern is the subject of
      a large literature that interprets it in terms of ecological processes, typically
      involving the sorting of differently specialized species onto heterogeneous
      landscapes. All of these patterns can be shown to arise, however, from neutral
      community models in which all individuals have identical properties, as the
      consequence of local dispersal alone. This implies, at the least, that functional
      interpretations of these patterns must be reevaluated. More fundamentally,
      neutral community models provide a general theory for biodiversity and
      conservation biology capable of predicting the fundamental processes and patterns
      of community ecology.

PMID- 11577229
TI  - Distributed and overlapping representations of faces and objects in ventral
      temporal cortex.
AB  - The functional architecture of the object vision pathway in the human brain was
      investigated using functional magnetic resonance imaging to measure patterns of
      response in ventral temporal cortex while subjects viewed faces, cats, five
      categories of man-made objects, and nonsense pictures. A distinct pattern of
      response was found for each stimulus category. The distinctiveness of the
      response to a given category was not due simply to the regions that responded
      maximally to that category, because the category being viewed also could be
      identified on the basis of the pattern of response when those regions were
      excluded from the analysis. Patterns of response that discriminated among all
      categories were found even within cortical regions that responded maximally to
      only one category. These results indicate that the representations of faces and
      objects in ventral temporal cortex are widely distributed and overlapping.

PMID- 11577230
TI  - Field-induced superconductivity in a spin-ladder cuprate.
AB  - We report on the modulation of the transport properties of thin films, grown by
      molecular beam epitaxy, of the spin-ladder compound [CaCu2O3]4, using the field
      effect in a gated structure. At high hole-doping levels, superconductivity is
      induced in the nominally insulating ladder material without the use of high
      pressure or chemical substitution. The observation of superconductivity is in
      agreement with the theoretical prediction that holes doped into spin ladders
      could pair and possibly superconduct.

PMID- 11577231
TI  - Restricting dislocation movement in transition metal carbides by phase stability
      tuning.
AB  - A mechanism to enhance hardness in multilayer coatings is proposed. Using the
      technologically important hard transition metal carbides as prototypes, although
      the principle is transferable also to other systems, we demonstrate, from first
      principles calculations, that by suitable alloying the energy difference between
      several competing structures in the transition metal carbides is small or
      tunable. This creates multiphase/polytypic compounds with a random or
      controllable layer stacking sequence, systems in which the propagation of
      dislocations can be strongly suppressed by a large number of interfaces between
      structures with different glide systems, accordingly allowing the possibility of
      a greatly enhanced hardness. With modern thin-film technologies, it should
      therefore be possible to deposit such materials that will express multilayer
      characteristics with only minor changes in the chemical constitution of the
      material, which is in contrast to conventional superlattices.

PMID- 11577232
TI  - Stability and structure of MgSiO3 perovskite to 2300-kilometer depth in Earth's
      mantle.
AB  - Unexplained features have been observed seismically near the middle
      (approximately 1700-kilometer depth) and bottom of the Earth's lower mantle, and
      these could have important implications for the dynamics and evolution of the
      planet. (Mg,Fe)SiO3 perovskite is expected to be the dominant mineral in the deep
      mantle, but experimental results are discrepant regarding its stability and
      structure. Here we report in situ x-ray diffraction observations of (Mg,Fe)SiO3
      perovskite at conditions (50 to 106 gigapascals, 1600 to 2400 kelvin) close to a
      mantle geotherm from three different starting materials, (Mg0.9Fe0.1)SiO
      enstatite, MgSiO3 glass, and an MgO+SiO2 mixture. Our results confirm the
      stability of (Mg,Fe)SiO3 perovskite to at least 2300-kilometer depth in the
      mantle. However, diffraction patterns above 83 gigapascals and 1700 kelvin (1900
      kilometer depth) cannot presently rule out a possible transformation from Pbnm
      perovskite to one of three other possible perovskite structures with space group
      P2(1)/m, Pmmn, or P4(2)/nmc.

PMID- 11577233
TI  - ENSO-like forcing on oceanic primary production during the Late Pleistocene.
AB  - Late Pleistocene changes in oceanic primary productivity along the equator in the
      Indian and Pacific oceans are revealed by quantitative changes in nanoplankton
      communities preserved in nine deep-sea cores. We show that variations in
      equatorial productivity are primarily caused by glacial-interglacial variability
      and by precession-controlled changes in the east-west thermocline slope of the
      Indo-Pacific. The precession-controlled variations in productivity are linked to
      processes similar to the Southern Oscillation phenomenon, and they precede
      changes in the oxygen isotopic ratio, which indicates that they are not the
      result of ice sheet fluctuations. The 30,000-year spectral peak in the tropical
      Indo-Pacific Ocean productivity records is also present in the Antarctica
      atmospheric CO2 record, suggesting an important role for equatorial biological
      productivity in modifying atmospheric CO2.

PMID- 11577234
TI  - Embryonic skulls of titanosaur sauropod dinosaurs.
AB  - Little is known about the cranial anatomy of the taxonomically diverse and
      geographically widespread titanosaurs, a paucity that has hindered inferences
      about the genealogical history and evolutionary development of the latest
      sauropod dinosaurs. Newly discovered fossil eggs containing embryonic remains
      from the Late Cretaceous of Argentina provide the first articulated skulls of
      titanosaur dinosaurs. The nearly complete fetal skulls shed light on the
      evolution of some of the most notable cranial features of sauropod dinosaurs,
      including the retraction of the external nares, the forward rotation of the
      braincase, and the abbreviation of the infraorbital region.

PMID- 11577235
TI  - Effects of helpers on juvenile development and survival in meerkats.
AB  - Although breeding success is known to increase with group size in several
      cooperative mammals, the mechanisms underlying these relationships are uncertain.
      We show that in wild groups of cooperative meerkats, Suricata suricatta,
      reductions in the ratio of helpers to pups depress the daily weight gain and
      growth of pups and the daily weight gain of helpers. Increases in the daily
      weight gain of pups are associated with heavier weights at independence and at 1
      year of age, as well as with improved foraging success as juveniles and higher
      survival rates through the first year of life. These results suggest that the
      effects of helpers on the fitness of pups extend beyond weaning and that helpers
      may gain direct as well as indirect benefits by feeding pups.

PMID- 11577236
TI  - Trans-suppression of misfolding in an amyloid disease.
AB  - The transthyretin (TTR) amyloid diseases, representative of numerous misfolding
      disorders, are of considerable interest because there are mutations that cause or
      suppress disease. The Val30 --> Met30 (V30M) TTR mutation is the most prevalent
      cause of familial amyloid polyneuropathy in heterozygotes, whereas a Thr119 -->
      Met119 (T119M) mutation on the second TTR allele protects V30M carriers from
      disease. Here, we show that the incorporation of one or more T119M TTR subunits
      into a predominantly V30M tetramer strongly stabilized the mixed tetramer against
      dissociation. Dissociation is required for amyloid formation, so these findings
      provide a molecular explanation for intragenic trans-suppression of amyloidosis.
      The data also suggest a potential therapeutic strategy, provide insight into
      tissue-specific deposition and amyloid composition, and support the validity of
      the amyloid hypothesis in human disease.

PMID- 11577237
TI  - Strand-specific postreplicative processing of mammalian telomeres.
AB  - Telomeres are specialized nucleoprotein structures that stabilize the ends of
      linear eukaryotic chromosomes. In mammalian cells, abrogation of telomeric repeat
      binding factor TRF2 or DNA-dependent protein kinase (DNA-PK) activity causes end
      to-end chromosomal fusion, thus establishing an essential role for these proteins
      in telomere function. Here we show that TRF2-mediated end-capping occurs after
      telomere replication. The postreplicative requirement for TRF2 and DNA-PKcs, the
      catalytic subunit of DNA-PK, is confined to only half of the telomeres, namely,
      those that were produced by leading-strand DNA synthesis. These results
      demonstrate a crucial difference in postreplicative processing of telomeres that
      is linked to their mode of replication.

PMID- 11577238
TI  - Dendrodendritic inhibition through reversal of dopamine transport.
AB  - Synapses in the central nervous system are usually defined by presynaptic
      exocytotic release sites and postsynaptic differentiations. We report here a
      demonstration of dendrodendritic inhibition that does not engage a conventional
      synapse. Using amperometric and patch-clamp recordings in rat brain slices of the
      substantia nigra, we found that blockade of the dopamine transporter abolished
      the dendritic release of dopamine and the resulting self-inhibition. These
      findings demonstrate that dendrodendritic autoinhibition entails the carrier
      mediated release of dopamine rather than conventional exocytosis. This suggests
      that some widely used antidepressants that inhibit the dopamine transporter may
      benefit patients in the early stages of Parkinson's disease.

PMID- 11577239
TI  - A cortical area selective for visual processing of the human body.
AB  - Despite extensive evidence for regions of human visual cortex that respond
      selectively to faces, few studies have considered the cortical representation of
      the appearance of the rest of the human body. We present a series of functional
      magnetic resonance imaging (fMRI) studies revealing substantial evidence for a
      distinct cortical region in humans that responds selectively to images of the
      human body, as compared with a wide range of control stimuli. This region was
      found in the lateral occipitotemporal cortex in all subjects tested and
      apparently reflects a specialized neural system for the visual perception of the
      human body.

PMID- 11577241
TI  - Sema3a is produced by brown adipocytes and its secretion is reduced following
      cold acclimation.
AB  - Heat production in brown adipose tissue (BAT) and brown adipocyte recruitment
      depend heavily on BAT vascular and parenchymal sympathetic and sensory
      innervation. The expression and distribution of Sema3a, a recently discovered
      chemorepellent neuronal factor active on both sympathetic and sensory peripheral
      nerves, were studied in interscapular rat BAT. In rats maintained in
      thermoneutral conditions, brown adipocytes produced both active isoforms of
      Sema3a and showed a distinct peripheral polarized immunostaining pattern. This
      suggests a role for Sema3a secreted by brown adipocytes in the guidance of axons
      toward their correct targets. In cold-acclimated rats, where parenchymal nerve
      density is higher, both the expression and the immunostaining of the two active
      isoforms were slightly but significantly reduced and the distinct staining
      pattern was not observed. These data suggest that the secretion of Sema3a is
      inhibited in the brown adipocytes of cold-acclimated rats. Thus, Sema3a could
      play a role in the plastic adjustment of BAT innervation observed in different
      conditions of functional demand.

PMID- 11577242
TI  - Early development of rat ventral root transitional zone: an immunohistochemical
      and morphometric study.
AB  - Bundles of ventral motoneuron axons cross the white matter of the spinal cord,
      emerge through the cord surface at the CNS-PNS transitional zone (TZ) and
      continue in the PNS as ventral rootlets. This study identifies
      immunohistochemical and morphometric changes which characterise the key events in
      early TZ formation in the rat. E18 is a landmark stage, since it is then that the
      major events of TZ differentiation are initiated. In the glial processes
      associated with the TZ, vimentin expression decreases, while that of GFAP
      increases. In the proximal rootlets the transient expression of CNS markers such
      as GFAP and of neural adhesion molecules such as HNK-1/N-CAM begin to decrease.
      Their resulting differential expression clearly defines the CNS-PNS interface.
      These changes coincide with the arrival of glial nuclei at the TZ. Cell clusters
      which appear on proximal ventral rootlet surfaces shortly after their emergence
      from the cord, have by E18 formed an extensive matrix of processes which
      segregates the axon bundle. This comprises the earliest of two well-defined
      barriers across the axon bundle. An important function may be to prevent Schwann
      cell invasion of the cord. Cluster cells display some immunohistochemical
      features in common with Schwann cells. The second barrier becomes fully
      established only at P2 and forms the definitive CNS-PNS interface. It consists of
      processes arising from astrocytes surrounding the TZ. Changes in the nuclear
      density of the cell types correspond closely to their segregating activity. The
      immunohistochemical and ultrastructural changes complement one another to deepen
      and enhance understanding of TZ development.

PMID- 11577243
TI  - Immunocytochemical localization of acyl-CoA oxidase in the rat central nervous
      system.
AB  - Peroxisomal beta-oxidation, consisting of four steps catalysed by an acyl-CoA
      oxidase, a multifunctional protein and a thiolase, is responsible for the
      shortening of a variety of lipid compounds. The first reaction of this pathway is
      catalysed by a FAD-containing acyl-CoA oxidase, three isotypes of which have been
      so far recognised. Among these, straight-chain acyl-CoA oxidase (ACOX) acts on
      long and very long chain fatty acids, prostaglandins and some xenobiotics. We
      investigated ACOX localisation by means of a sensitive, tyramide based,
      immunocytochemical technique, thus obtaining a complete distribution atlas of the
      enzyme in adult rat CNS. Granular immunoreaction product was found in the
      cytoplasm of neuronal and glial cells, both in the perikarya and in the cell
      processes. ACOX immunoreactive neurons were present to variable extent, in either
      forebrain or hindbrain areas. Specifically, the strongest signal was detected in
      the pallidum, septum, red nucleus, reticular formation, nuclei of the cranial
      nerves, and motoneurons of the spinal cord. We then compared the ACOX
      immunoreactivity pattern with our previous distribution maps of other peroxisomal
      enzymes in the adult rat brain. While ACOX appeared to colocalise with catalase
      in the majority of cerebral regions, some differences with respect to d-amino
      acid oxidase were noted. These observations support the hypothesis of
      heterogeneous peroxisomal populations in the nervous tissue. The wide
      distribution of the enzyme in the brain is consistent with the severe and
      generalised neurological alterations characterising the peroxisomal disorder
      caused by ACOX deficiency (pseudo-neonatal adrenoleukodystrophy).

PMID- 11577244
TI  - Contractile proteins in pericytes at the blood-brain and blood-retinal barriers.
AB  - Evidence from a variety of sources suggests that pericytes have contractile
      properties and may therefore function in the regulation of capillary blood flow.
      However, it has been suggested that contractility is not a ubiquitous function of
      pericytes, and that pericytes surrounding true capillaries apparently lack the
      machinery for contraction. The present study used a variety of techniques to
      investigate the expression of contractile proteins in the pericytes of the CNS.
      The results of immunocytochemistry on cryosections of brain and retina, retinal
      whole-mounts and immunoblotting of isolated brain capillaries indicate strong
      expression of the smooth muscle isoform of actin (alpha-SM actin) in a
      significant number of mid-capillary pericytes. Immunogold labelling at the
      ultrastructural level showed that alpha-SM actin expression in capillaries was
      exclusive to pericytes, and endothelial cells were negative. Compared to alpha-SM
      actin, non-muscle myosin was present in lower concentrations. By contrast, smooth
      muscle myosin isoforms, were absent. Pericytes were strongly positive for the
      intermediate filament protein vimentin, but lacked desmin which was consistently
      found in vascular smooth muscle cells. These results add support for a
      contractile role in pericytes of the CNS microvasculature, similar to that of
      vascular smooth muscle cells.

PMID- 11577245
TI  - An oscillating extracellular voltage gradient reduces the density and influences
      the orientation of astrocytes in injured mammalian spinal cord.
AB  - We have studied the cellular basis for recovery from acute spinal cord injury
      induced by applied electric fields. We have emphasized this recovery is due to
      the regeneration of spinal axons around and through the lesion, and have begun to
      evaluate the contribution of other cells to the recovery process. We have imposed
      a voltage gradient of about 320 microV/mm across puncture wounds to the adult rat
      spinal cord in order to study the accumulation and orientation of GFAP+
      astrocytes within and adjacent to the lesion. This electric field was imposed by
      a miniaturized electronic implant designed to alternate the polarity of the field
      every 15 minutes. Astrocytes are known to undergo hyperplastic transformation
      within injured mammalian cords forming a major component of the scar that forms
      in response to injury. We have made three observations using a new computer based
      morphometry technique: First, we note a slight shift in the orientation of
      astrocytes parallel to the long axis of the spinal cord towards an imaginary
      reference perpendicular to this axis by approximately 10 degrees--but only in
      undamaged white matter near the lesion. Second, the relative number of astrocytes
      was markedly, and statistically significantly, reduced within electrically-
      treated spinal cords, particularly in the lesion. Third, the imposed voltage
      gradient statistically reduced the numbers of astrocytes possessing oriented cell
      processes within the injury site compared to adjacent undamaged regions of spinal
      cord.

PMID- 11577246
TI  - Inhibitory effect of aluminium on the axonal transport of HRP microinjected into
      dorsal root ganglion neurons in vitro.
AB  - In the present study the function of axonal transport in individual neurons under
      aluminium intoxication was investigated experimentally in comparison with
      controls. We used the technique of microinjection of horseradish peroxidase (HRP)
      in dissociated dorsal root ganglia (DRG) neurons and neurons of explant cultures
      of DRG. Different exposure periods (1 and 6 hours as well as 6 and 10 days) to
      aluminium were analysed quantitatively. This analysis revealed an impaired
      anterograde transport of HRP already after a short aluminium intoxication period
      of only 1 hour in DRG cells in vitro, an effect that increased with a prolonged
      aluminium exposure for up to 10 days. Hence, functional alterations of the
      anterograde transport caused by aluminium could be detected even after short
      exposure periods. Furthermore, the effects of aluminium on anterograde transport
      mechanisms were reversible 8 days after removal of aluminium. To determine how
      aluminium affects the cytoskeleton, we performed immunohistochemistry and
      electron microscopy on cultured DRG neurons. Distinct morphological alterations
      of the cytoskeleton, especially the accumulation of phosphorylated
      neurofilaments, appeared after 6 days of aluminium exposure. Our results suggest
      that neurofilaments are indispensable to the functional integrity of the
      cytoskeleton and its ability to mediate microtubule-based axonal transport
      processes.

PMID- 11577247
TI  - Ontogenesis of the snail, Helix aspersa: embryogenesis timetable and ontogenesis
      of GABA-like immunoreactive neurons in the central nervous system.
AB  - Late stages of embryogenesis in the terrestrial snail Helix aspersa L. were
      studied and a developmental timetable was produced. The distribution of gamma
      aminobutyric acid-like immunoreactive (GABA-ir) elements in the CNS of the snail
      was studied from embryos to adulthood in wholemounts. In adults, approximately
      226 GABA-ir neurons were located in the buccal, cerebral and pedal ganglia. The
      population of GABA-ir cells included four pairs of buccal neurons, three neuronal
      clusters in the pedal ganglia, two clusters and six single neurons in the
      cerebral ganglia. GABA-ir fibers were observed in all ganglia and in some nerves.
      The first detected pair of GABA-ir cells in the embryos appeared in the buccal
      ganglia at about 63-64% of embryonic development. Five pairs of GABA-ir cell
      bodies were observed in the cerebral ganglia at about 64-65% of development.
      During the following 30% of development three more pairs of GABA-ir neurons were
      detected in the buccal ganglia and over fifteen cells were detected in each
      cerebral ganglion. At the stage of 70% of development, the first pair of GABA-ir
      neurons was found in the pedal ganglia. In the suboesophageal ganglion complex,
      GABA-ir fibers were first detected at about 90% of embryonic development. In the
      posthatching period, the quantity of GABA-ir neurons reached the adult status in
      four days in the cerebral ganglia, and in three weeks in the pedal ganglia. In
      juveniles, transient expression of GABA was found in the pedal ganglia (fourth
      cluster).

PMID- 11577248
TI  - Immunohistochemical evidence and ultrastructural compartmentalization of a new
      antioxidant enzyme in the rat substantia nigra.
AB  - We previously described in the rat the presence of dehydroascorbate reductase, an
      enzyme regenerating ascorbic acid, which is constantly lost during oxidative
      processes occurring at a fast rate within the central nervous system. In the
      present study, we specifically evaluate the occurrence of this enzyme in the rat
      substantia nigra by using immunohistochemistry, and by analyzing the neuronal
      compartmentalization of dehydroascorbate reductase within nigral neurons by
      immunoblotting and transmission electron microscopy coupled with
      immunocytochemistry. The enzyme occurs in various portions of the substantia
      nigra, but it is more abundant in the ventromedial part extending through the
      ventral tegmental area, and the dorsal portion, involving the pars compacta.
      Within nigral neurons, the cytosolic enzyme is present in a perinuclear position,
      close to mitochondria, and in the nuclear membrane; we also found the enzyme in
      nigral axons close to the myelin sheath. In addition, dehydroascorbate reductase
      was present in the nucleus of nigral neurons. The nuclear occurrence of the
      enzyme was confirmed by immunocytochemical labelling and immunoblotting of
      isolated nuclei. The nuclear enzyme was constantly evident as clusters of
      immunogold particles on chromatin. This localization suggests new roles for
      dehydroascorbate reductase (eg. prevention of DNA oxidative damage and regulation
      of gene transcription).

PMID- 11577249
TI  - Immunolocalization of occludin and claudin-1 to tight junctions in intact CNS
      vessels of mammalian retina.
AB  - The distributions of occludin and claudin-1, two tight junction-associated
      integral membrane proteins were investigated by immunohistochemical analysis of
      whole-mount preparations of the blood vessels in the myelinated streak of the
      rabbit retina. Light microscopy revealed that occludin and claudin-1
      immunoreactivities were abundant along the interface of adjacent endothelial
      cells of all blood vessels. Electron microscopy revealed that both proteins were
      distributed in a regular pattern (at regular intervals of approximately 80 nm)
      along the length of tight junctions, probably in the regions of tight junction
      strands. No other structures or cell types expressed either of these two proteins
      in the myelinated streak. Whereas occludin immunoreactivity was concentrated only
      at the tight junction interface, claudin-1 immunoreactivity also extended into
      the cytoplasm of the endothelial cells, suggesting a different structural role
      for claudin-1 than for occludin at tight junctions. Retinal pigment epithelial
      cells expressed occludin around their entire circumference, consistent with the
      function of these cells as a barrier separating the retina from the leaky vessels
      of the choroid. Also consistent with the association of occludin expression with
      vessels that exhibit functional tight junctions, this protein was expressed at
      only a low level in, and showed an irregular distribution along, the vessels of
      the choroid, a vascular bed that lacks blood-barrier properties. Further, the
      distribution of occludin was examined during formation and remodelling of the rat
      retinal vasculature. Occludin expression was evident at the leading edge of
      vessel formation and was found on all vessels in both the inner and outer
      vascular plexus. Numerous vascular segments at the early stage of vascular
      formation and regression lost occludin expression. The biological significance of
      this transient loss of occludin expression in terms of barrier function remains
      to be elucidated.

PMID- 11577250
TI  - Sciatic nerve transection in neonatal rats induces apoptotic neuronal death in L5
      dorsal root ganglion.
AB  - Transection of a peripheral nerve in neonatal rats induces death of the
      axotomized neurons which may be due to either necrosis or apoptosis. In the
      present investigation, neuronal cell death in L5 dorsal root ganglion was
      evaluated after unilateral sciatic nerve transection in rats at 1, 3, 5, 7 and 10
      days age. After 5 days, right (experimental) and left (control) dorsal root
      ganglia in all groups were removed, fixed, processed and embedded for either
      light or electron microscopy. Normal nucleoli were counted in paraffin embedded
      serial sections, and correction factors for split and multiple nucleoli were
      applied as well as the physical disector. The number of neurons in the right
      dorsal root ganglia, as compared with the controls, was significantly lower in
      all groups, and the percentage of the reduction at 1, 3, 5, 7 and 10 days was
      32.4, 27.2, 23.8, 22.8 and 21.8% respectively. On the other hand, the results of
      neuronal counts using the disector method showed 34.0, 25.7, 20.2, 20.0 and 14.2%
      reduction in the number of neurons at 1, 3, 5, 7 and 10 days, respectively. The
      microscopic and ultrastructural results indicated that there were typical
      morphological changes similar to those of apoptosis, including condensed
      basophilic nuclei, formation of nuclear caps, cell shrinkage and apoptotic body
      formation. We concluded that there is an increase in apoptosis in dorsal root
      ganglia following sciatic nerve axotomy with the greatest neuronal loss on
      postnatal day 1.

PMID- 11577251
TI  - Retinal pigment epithelium melanin granules are phagocytozed by Muller glial
      cells in experimental retinal detachment.
AB  - The ability of retinal Muller glial cells to perform phagocytosis in vivo is
      studied in a rabbit model of experimental retinal detachment where pigment
      epithelial cells are occasionally detached together with the neural retina. While
      macrophages and/or microglial cells phagocytoze most of the cellular debris at
      the sclerad surface of the detached retinae, some Muller cells accumulate melanin
      granules. The granules are virtually intact at the ultrastructural level, and are
      surrounded by a membrane. They are often located close to the sclerad end of the
      cells, but some are distributed throughout the outer stem process up to the soma.
      It is concluded that rabbit Muller cells in vivo are capable of phagocytosis and
      of transporting the phagocytozed material within their cytoplasm.

PMID- 11577252
TI  - Expression of the group II and III metabotropic glutamate receptors in the
      hippocampus of patients with mesial temporal lobe epilepsy.
AB  - By immunocytochemical study by both light and electron microscopy of the
      hippocampus of patients with mesial temporal lobe epilepsy, we have shown that
      mGluR2/3 and mGluR4alpha immunoreaction product was mainly localised in the
      molecular layer of the dentate gyrus and CA2 area. Electron microscopy showed
      that most of the immunoreaction product due to mGluR2/3, 4a and 8 was deposited
      in the postsynaptic elements of the CA2 pyramidal layer and the inner molecular
      layer of the dentate gyrus. Only mGluR8 immunoreaction product in the CA2 area
      and mGluR2/3 in the inner molecular layer of the dentate gyrus were demonstrated
      in presynaptic elements, suggesting that mGluR2/3 and 8 may be involved in
      presynaptic inhibition of glutamate release in these areas. The demonstration of
      some degenerating axon terminals in the inner molecular layer of the dentate
      gyrus suggests that degeneration of interneurons caused by repeated seizures was
      still in progress. The finding of mGluR2/3, 4 and 8 immunoreactive astrocytes in
      patient hippocampus suggests that mGluR2/3, 4 and 8 receptors may be involved in
      gliosis.

PMID- 11577253
TI  - Differential phosphorylation of tau proteins during kitten brain development and
      Alzheimer's disease.
AB  - Differential distribution and phosphorylation of tau proteins were studied in
      developing kitten brain by using several antibodies, and was compared to
      phosphorylation in Alzheimer's disease. Several antibodies demonstrated the
      presence of phosphorylated tau proteins during kitten brain development and
      identified pathological structures in human brain tissue. Antibody AD2,
      recognized tau in kittens and adult cats, but reacted in Alzheimer's tissue only
      with a pathological tau form. Antibody AT8 was prominent in developing kitten
      neurons and was found in axons and dendrites. After the first postnatal month
      this phosphorylation type disappeared from axons. Furthermore, dephosphorylation
      of kitten tau with alkaline phosphatase abolished immunoreactivity of AT8, but
      not that of AD2, pointing to a protection of the AD2 epitope in cats. Tau
      proteins during early cat brain development are phosphorylated at several sites
      that are also phosphorylated in paired helical filaments during Alzheimer's
      disease. In either event, phosphorylation of tau may play a crucial role to
      modulate microtubule dynamics, contributing to increased microtubule instability
      and promoting growth of processes during neuronal development or changing dynamic
      properties of the cytoskeleton and contributing to the formation of pathological
      structures in neurodegenerative diseases.

PMID- 11577254
TI  - On the connection between the T-system and the subsynaptic folds in the motor end
      plate of amphibians.
AB  - Using lanthanum as an extracellular marker, the transition between the
      subsynaptic folds of the motor end plate and the T-system of frog muscle fibres
      is portrayed for the first time. On the lower segment of the subsynaptic folds of
      frogs, there are numerous caveolae which can connect with one another to form
      meandering, branching tubes. The T-system is in contact with these tubes (which
      run through the sarcoplasm) beneath the motor end plate. In those segments of the
      end plate with massed sarcoplasm and a cell nucleus, these tubes form networks in
      close proximity to the cellular organelles. The morphological findings obtained
      here are compared with findings from mammals. The physiological significance of
      the transition between the subsynaptic fold and the T-system is discussed.

PMID- 11577255
TI  - Effect of a single embryonic exposure to alcohol on glucose transporter (GLUT-1)
      distribution in brain vessels of aged mouse.
AB  - Distribution of glucose transporter (GLUT-1) in brain microvascular endothelium,
      representing the anatomic site of the blood-brain barrier (BBB), was studied with
      electron microscopy in 24-month-old mice, which had been exposed prenatally (on
      9th day of gestation) to a single teratogenic dose of ethanol. Offspring of mice
      that had received an equivalent volume of isocaloric dextrose served as controls.
      Sections of brain samples embedded at low temperature in hydrophilic resin
      Lowicryl K4M were exposed to anti-GLUT-1 antiserum followed by gold-labelled
      secondary antibodies. By using morphometry, the labelling density was recorded
      over luminal and abluminal plasma membranes of the endothelial cells of blood
      microvessels supplying four brain regions: cortex, hippocampus, cerebellum and
      olfactory bulb. We found that the density of immunosignals for GLUT-1,
      represented by colloidal gold particles, was unchanged in the olfactory bulb and
      slightly lowered in the abluminal plasmalemma of the vascular endothelium in the
      cerebral cortex of the ethanol-treated mice. In contrast, statistical analysis
      using Mann-Whitney U-test revealed that in the hippocampus and cerebellum, the
      density of immunolabelling of both plasma membranes of microvascular endothelial
      cells was significantly lowered in the ethanol-treated mice. These findings
      suggest that prenatally applied ethanol had a different influence on the
      vasculature supplying different brain regions. In effect, the inefficient supply
      of glucose to selected brain regions can be one of the factors leading to the
      previously observed deficit in long-term memory in a similar alcohol-treated
      group of mice.

PMID- 11577256
TI  - Plasminogen activator inhibitor type-1 (part one): basic mechanisms, regulation,
      and role for thromboembolic disease.
AB  - Plasminogen activator inhibitor type-1 (PAI-1) is a rapid inhibitor of tissue
      plasminogen activator (tPA) in circulation. Evidence suggests that the PAI-1
      concentration is responsible for the regulation of the endogenous fibrinolytic
      system through its tPA/PAI-1 interactions. Accordingly, increased levels of PAI-1
      have emerged as a masker for an increased thrombolic risk. This article
      represents a status report of mechanism of action, regulation of plasma levels,
      as well as the role of PAI-1 in arterial and venous thromboembolic disease.

PMID- 11577257
TI  - Plasminogen activator inhibitor type-1 (part two): role for failure of
      thrombolytic therapy. PAI-1 resistance as a potential benefit for new
      fibrinolytic agents.
AB  - Rapid and sustained reperfusion of an occluded coronary artery is the goal of
      thrombolytic therapy in acute myocardial infarction. However, the clot-dissolving
      efficacy of fibrinolytic agents such as tissue-type plasminogen activator (t-PA)
      is limited, in vivo, in part by the action of plasminogen activator inhibitor
      type-1 (PAI-1). A new generation of fibrinolytic agents has been genetically
      engineered to have greater resistance to PAI-1 inhibition. This article reviews
      the pathophysiologic role of PAI-1 in failure of thrombolytic therapy and
      describes the advantages that PAI-1-resistance may confer upon fibrinolytic
      agents such as TNK-t-PA, the new fibrinolytic agent with the most powerful PAI-1
      resistance.

PMID- 11577258
TI  - Short-term comparative outcomes associated with the use of GP IIb/IIIa
      antagonists in patients undergoing coronary intervention.
AB  - BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa antagonists reduce the occurrence
      of death, myocardial infarction (MI) and urgent revascularization among patients
      undergoing percutaneous coronary intervention (PCI). Despite a similar mechanism
      of platelet inhibition, the three currently approved agents vary widely in cost.
      PURPOSE: The purpose of this prospectively designed, retrospective analysis was
      to determine clinical outcomes for patients receiving abciximab, tirofiban or
      eptifibatide as adjunctive therapy during PCI at a single center. We hypothesized
      that there would be no difference in outcomes during hospitalization following
      PCI in patients receiving tirofiban or eptifibatide compared with those patients
      who received abciximab. Outcomes examined included in-hospital mortality,
      hemorrhagic procedural complications, need for recatheterization, peak creatine
      kinase following intervention and length of hospital stay (LOS). RESULTS: Two
      hundred and sixty seven consecutive patients in whom GP IIb/IIIa antagonist
      therapy was initiated in the catheterization laboratory for PCI were analyzed.
      Abciximab-treated patients were more likely to be undergoing primary (p<0.001)
      and rescue (p=0.022) PCI and to have received fibrinolytic therapy (p=0.013) when
      compared to patients receiving tirofiban or eptifibatide. There were no
      significant differences between abciximab- and non abciximab-treated patients in
      either the primary PCI or non primary PCI groups in any of the studied endpoints.
      In patients undergoing primary PCI, abciximab-treated patients when compared with
      non abciximab-treated patients exhibited a trend toward an increase in hospital
      LOS (7.8+/-7.0 d vs 6.2+/-3.9, p=0.19) and in the frequency of hemorrhagic
      complications (22.1% vs 5.3%, p=0.11). In patients not receiving fibrinolytic
      therapy, abciximab-treated patients experienced a trend toward increased
      hemorrhagic complications following PCI when compared to non abciximab-treated
      patients (10.2% vs 6.0%, p=0.28). Complications distant from the vascular access
      site comprised 62.5% of hemorrhagic complications in the abciximab-treated group,
      but only 20% of the complications in the non-abciximab treated population
      (p<0.001). These data suggest no differences in acute outcomes between groups of
      patients receiving abciximab or other approved GP IIb/IIIa antagonists
      highlighting a potential significant cost saving. These data will require
      interpretation following the publication of comparative trials.

PMID- 11577259
TI  - Elevation in serum troponin I predicts the benefit of tirofiban.
AB  - BACKGROUND: Elevations in serum troponins among patients with acute coronary
      syndromes have been shown to identify those patients who are at high risk for
      poor outcome and who accrue larger relative benefits from aggressive antiplatelet
      and antithrombotic therapies. We studied a group of patients from the PRISM-PLUS
      trial to explore whether simply using serum troponin I, a serum marker of cardiac
      injury, could predict benefit of GP IIb/IIIa receptor antagonism with tirofiban.
      METHODS AND RESULTS: For this study, the subjects consisted of 55 patients
      receiving the combination therapy of tirofiban/heparin, and 55 receiving heparin
      alone. The baseline characteristics were similar between the two treatment
      groups. Serial blood samples were obtained over the first 24-hour period
      following randomization to study drug, and were analyzed for troponin I (TnI)
      levels. Among those patients with elevated serum TnI (>0.5 ng/ml), the 30-day
      event rate for death or myocardial infarction (MI) was reduced from 20.6% among
      the heparin only group to 3.6% for those treated with the combination of
      tirofiban/heparin, an absolute risk reduction of 17% and relative risk reduction
      of 83% (p=0.06). Among the TnI negative patients, the rates of death/MI at 30
      days were 9.5% and 11.1% among the combination and heparin treated groups
      respectively (p=NS). CONCLUSION: Irrespective of high-risk clinical factors,
      including ST segment depression, these data support the hypothesis that serum
      troponins identify those who benefit from aggressive antiplatelet therapy with
      tirofiban.

PMID- 11577260
TI  - Relationship between the heparin management test and the HemoTec activated
      clotting time in patients undergoing percutaneous coronary intervention.
AB  - Point-of-care whole blood coagulation tests are critical in the management of
      patients who undergo percutaneous coronary intervention. The Hemochron and
      HemoTec devices have been traditionally used to measure the activated clotting
      time (ACT) in the cardiac catheterization laboratory. The heparin management test
      (HMT) was recently introduced into clinical practice as an alternative method to
      current ACT measurements that uses a different sample volume, contact activators
      and detection system to measure whole blood coagulation. We compared the HMT to
      the HemoTec ACT in 68 prospectively enrolled patients (127 blood samples)
      undergoing percutaneous coronary intervention. Measurements were performed 10
      minutes after the initial heparin bolus and thereafter at the discretion of the
      attending physician. The mean HMT was 41 seconds higher (approximately 15%) than
      the HemoTec ACT (HMT 304+/-59 vs. ACT 263+/-52, P< 0.0001), but there was a
      significant correlation between the methods (r=0.77, P<0.0001). However, there
      was increasing disagreement between the two methods as the level of
      anticoagulation increased. The relationship between HMT and ACT was similar in
      patients in whom glycoprotein IIb/IIIa inhibitors were used. The HMT, therefore,
      appears to be more sensitive to heparin anticoagulation that the HemoTec ACT and
      correlates well with it in the range required for percutaneous coronary
      intervention.

PMID- 11577261
TI  - Augmentation of in-vitro clot dissolution by low frequency high-intensity
      ultrasound combined with antiplatelet and antithrombotic drugs.
AB  - BACKGROUND: Glycoprotein IIb/IIIa antagonists and heparin are increasingly used
      for treatment of acute coronary syndromes. There is no data on the effect of
      these drugs on clot dissolution when combined with low frequency high-intensity
      ultrasonic energy. We examined a possible additive effect of low frequency high
      intensity ultrasound with an antithrombotic, an antiplatelet and a fibrinolytic
      agent alone or in combinations for in vitro blood clot dissolution. METHODS:
      Human blood clots were incubated for 10', 15' and 30' in normal saline containing
      commonly used concentrations of heparin, tirofiban, t-PA and Optison
      (echocardiographic contrast agent) alone and in combinations. Clots were then
      randomly exposed to low frequency high-intensity ultrasound (27[emsp3 ]kHz) for 5
      minutes. The percent difference in clot weight and the incremental effect of
      ultrasound energy were calculated. RESULTS: The most significant additive effect
      of ultrasound energy was detected with the combination of tirofiban and heparin
      (39+/-2% augmentation after 10' of incubation, p<0.0001). The greatest magnitude
      of percent clot weight reduction was observed with ultrasound energy combined
      with either t-PA alone (72+/-1% after 30' incubation, p=0.0016) or with the
      combination of t-PA, tirofiban, heparin and Optison (68+/-4% after 30'
      incubation, p=0.015). CONCLUSIONS: Application of low frequency high-intensity
      ultrasound has an additive effect to antiplatelet, antithrombotic and
      fibrinolytic drugs, specifically with the combination of tirofiban and heparin or
      with t-PA; this effect is observed after a short incubation period.

PMID- 11577262
TI  - Noninvasive transthoracic low frequency ultrasound augments thrombolysis in a
      canine model of acute myocardial infarction--evaluation of the extent of ST
      segment resolution.
AB  - BACKGROUND: Recently it has been demonstrated that transcutaneous delivery of
      ultrasound combined with tissue plasminogen activator (tPA) is more effective
      than tPA alone in recanalizing acutely thrombosed canine coronary arteries. In
      the present study, we investigated the incidence of partial (> or =50%) and
      complete (> or =70%) ST-segment elevation resolution in the precordial leads of
      dogs with experimental acute myocardial infarction that were treated with tissue
      plasminogen activator (tPA) alone or in combination with noninvasive
      transcutaneous delivery of high-intensity low frequency (27[emsp3 ]kHz)
      ultrasound. METHODS: Thrombotic coronary occlusions were induced in the
      midportion of left anterior descending (LAD) coronary artery by electrical injury
      in 24 dogs. All dogs were given intravenous heparin and tPA. Dogs were randomized
      to tPA alone (n=12) or combined tPA and adjunctive transcutaneous ultrasound (US)
      delivery (n=12). Electrocardiograms were recorded at 1) baseline, 2) after
      coronary occlusion just before initiation of therapy, 3) when coronary
      angiography showed recanalization of the coronary artery (or at 90 minutes after
      initiation of therapy if reperfusion did not occur before then) and 4) 90 minutes
      later. ST amplitude was measured in all 6 precordial leads. RESULTS: ST-segment
      amplitude at baseline was comparable between the tPA and the US group. Before
      initiation of therapy, sum of ST-segment elevation tended to be higher in the US
      group. At reperfusion and 90 minutes thereafter, sum of ST-segment amplitude
      tended to be smaller for the US group than in the tPA group (p<0.001 for the time
      effect; p=0.118 for the time x group interaction). Up to 90 minutes after
      initiation of therapy >/=50% resolution of the sum of precordial ST elevation was
      detected in 7 out of 11 dogs (63.6%) in the tPA group versus 10 out of 11 dogs
      (90.9%) in the US group. Ninety minutes thereafter, 3 out of 7 dogs in the tPA
      group (42.9%) versus 9 of 11 dogs in the US group (81.8%) had >/=50% resolution
      of the sum of precordial ST elevation. CONCLUSIONS: The combination of tPA with
      noninvasive transcutaneous delivery of low frequency high-intensity ultrasound
      resulted in greater resolution of ST-segment elevation when reperfusion occurs
      and 90 minutes thereafter, as well as a higher rate of epicardial coronary artery
      reperfusion.

PMID- 11577263
TI  - Low molecular weight heparin therapy for percutaneous coronary intervention: a
      practice in evolution.
AB  - Unfractionated heparin (UFH) remains the principal antithrombotic agent during
      percutaneous coronary intervention (PCI) but is associated with significant
      limitations including an unpredictable anticoagulation dose response, the
      requirement for frequent monitoring, and transient rebound hypercoagulability.
      Low molecular weight heparin (LMWH) represents an attractive alternative due to
      its predictable dose response relationship, superior antithrombotic efficacy and
      potential for improved clinical safety, and has been used increasingly in
      patients with acute coronary syndromes prior to coronary angiography. The
      rationale and existing data regarding the use of LMWH in PCI is summarized and
      reviewed. Preliminary clinical guidelines for the use of LMWH in the transition
      from medical stabilization of patients with acute coronary syndromes to invasive
      management in the catheterization laboratory are presented.

PMID- 11577264
TI  - Applying scientific criteria to therapeutic interchange: a balanced analysis of
      low-molecular-weight heparins.
AB  - Under pressure to provide cost-effective healthcare, many healthcare systems have
      adopted Therapeutic Interchange (TI) programs-the interchange of therapeutically
      equivalent but chemically unique drugs-to reduce the total cost of therapy
      without compromising patient care. To be appropriate and feasible, a TI program
      for any class of drugs must meet certain rigorous criteria and undergo medical,
      financial, tactical, and legal reviews. Moreover, once a TI program is
      implemented, a process to monitor its success should be established. Application
      of the TI criteria to low-molecular-weight heparins (LMWHs) reveals that a
      blanket TI program for LMWHs does not appear advisable at this time.

PMID- 11577265
TI  - Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS):
      the new thinking.
AB  - TTP and HUS are two disorders with many similarities. Though their first
      descriptions appeared at different time in history, there has been a trend among
      physicians to consider them as the same clinical entity. However, in recent years
      new research findings on the pathophysiology of TTP and HUS have revealed some
      differences between the two disorders. In this paper, we will review the current
      approaches to the clinical and laboratory diagnosis of TTP and HUS, as well as
      therapeutic strategies. We will also summarize the recent advances in three areas
      in the study of the pathophysiology of TTP and HUS, namely the newly discovered
      von Willebrand factor multimer-cleaving protease, endothelial cell apoptosis
      induced by serum from patients with TTP and atypical HUS and the activation of
      complement system. Since distinguishing and differentiating between TTP and HUS
      may help to develop more effective therapies targeted at key steps of the disease
      development, we will discuss possible ways of reclassifying the TTP-HUS
      disorders. In the end, we also present our views on possible future development.

PMID- 11577267
TI  - Contrast-enhanced near-infrared laser mammography with a prototype breast
      scanner: feasibility study with tissue phantoms and preliminary results of
      imaging experimental tumors.
AB  - RATIONALE AND OBJECTIVES: Near-infrared (NIR) optical mammography without
      contrast has a low specificity. The application of optical contrast medium may
      improve the performance. The concentration-dependent detectability of a new NIR
      contrast medium was determined with a prototype optical breast scanner. In vivo
      imaging of experimental tumors was performed. METHODS: The NIR contrast agent
      NIR96010 is a newly synthesized, hydrophilic contrast agent for NIR mammography.
      A concentration-dependent contrast resolution was determined for tissue phantoms
      consisting of whole milk powder and gelatin. A central part of the phantoms
      measuring 2 x 2 cm2 without contrast was replaced with phantom material
      containing 1 micromol/L to 25 nmol/L NIR96010. The composite phantoms were
      measured with a prototype NIR breast scanner with lasers of lambda1 = 785 nm and
      lambda2 = 850 nm wavelength. Intensity profiles and standard deviations of the
      transmission signal in areas with and without contrast were determined by linear
      fit procedures. Signal-to-noise ratios and spatial resolution as a function of
      contrast concentration were determined. Near-infrared imaging of five tumor
      bearing SCID mice (MX1 breast adenocarcinoma, tumor diameter 5-10 mm) was
      performed before and after intravenous application of 2 micromol/kg NIR96010.
      RESULTS: Spectrometry showed an absorption maximum of the contrast agent at 755
      nm. No spectral shifts occurred in protein-containing solution. Signal-to-noise
      ratio in the transmission intensity profiles ranged from 1.1 at 25 nmol/L
      contrast to 28 at 1 micromol/L. At concentrations <40 nmol/L, no differentiation
      from the background was possible. The transitional area between the contrast-free
      edge of the phantom and the central contrast-containing part appeared in the
      profiles as a steep increase with a width of 4.2 +/- 1.8 mm. The experimental
      tumors were detectable in nonenhanced images as well as contrast-enhanced images,
      with better delineation after contrast administration. In postcontrast absorption
      profiles, a 44.1% +/- 11.3% greater absorption increase was seen in tumor tissue
      compared with normal tissue. CONCLUSIONS: The laser wavelength lambda1 of the
      prototype laser mammography device was not situated at maximum absorption of the
      contrast agent NIR96010 but on the descending shoulder of the absorption
      spectrum. This implies a 20% signal loss for contrast detection. Despite the
      nonideal measurement conditions, concentrations as low as 40 nmol/L were
      detectable in vitro. In vivo, all tumors were detectable in color-coded
      nonenhanced scans as well as in contrast-enhanced scans, with better delineation
      after contrast administration.

PMID- 11577266
TI  - Comparative study between gadobenate dimeglumine and gadobutrol in rats with
      brain ischemia: evaluation of somatosensory evoked potentials.
AB  - RATIONALE AND OBJECTIVES: The present study had two main objectives: to validate
      a rat model of brain ischemia in terms of somatosensory evoked potentials (SEPs)
      and to compare, using the validated model, the potential activity on the
      somatosensory function of the new, approved contrast agent gadobenate dimeglumine
      with that of gadobutrol, a specific contrast agent, for magnetic resonance
      imaging of the brain. METHODS: Rats were prepared for SEP recording at least 5
      days before ischemia induction. Ischemia was induced by 30-minute right middle
      cerebral artery occlusion and 3-day reperfusion. The SEP responses, evoked
      contralaterally to the stimulated upper limb, were recorded from the primary
      somatosensory cortical area. Model validation, on day 3 after occlusion, was
      performed using iopromide, an iodinated contrast agent poorly neurotolerated in
      rats, intravenously injected at 7 g I/kg. The comparative study between
      gadobenate dimeglumine and gadobutrol was performed at an intravenously injected
      dose of 2 mmol/kg. Somatosensory evoked potential responses were measured as peak
      latencies (P2 and N2) and peak-to-peak amplitude (P2N2). The brain concentration
      of iopromide was measured by high-performance liquid chromatography, whereas that
      of the gadolinium contrast agent was measured by inductively coupled plasma
      atomic emission spectrometry analysis; given the absence of metabolism for both
      contrast agents, the gadolinium content values can be interpreted as representing
      unmetabolized contrast agent. RESULTS: In the ischemic rats, the SEP responses of
      the lesioned hemisphere showed significant increases in P2, N2, and interpeak N2
      P2 latencies and a significant reduction in peak-to-peak (P2N2) amplitude. In the
      validation experiments, iopromide dramatically increased the P2N2 amplitude of
      the SEP responses recorded from both hemispheres of ischemic rats without
      affecting the P2, N2, and interpeak N2-P2 latencies. The iopromide effect was
      coupled with high concentrations of the contrast agent in the brain. Iopromide
      had no effect on healthy rats. In the comparative study, gadobenate dimeglumine
      did not induce any alteration in SEP components of either the lesioned or
      unlesioned hemisphere of ischemic rats. In fact, no significant difference was
      found between responses obtained before and after gadobenate dimeglumine
      injection. Gadobutrol, administered at the same dose, on the whole showed the
      same behavior as gadobenate dimeglumine, although a slight but significant
      decrease in the P2 latency, a sign of excitatory activity, was observed 2 hours
      after injection. Analytic data indicated higher levels of contrast agent in the
      lesioned hemisphere versus the unlesioned hemisphere 2 hours after injection.
      CONCLUSIONS: Based on these results, three conclusions can be drawn: (1) the
      evaluation of SEPs in ischemic rats is a useful tool for assessing the potential
      neurological effects of a new contrast agent because ischemic and contrast agent
      effects can be clearly differentiated; (2) the experimental conditions used allow
      the contrast agents to penetrate into the brain, where their activity can be
      manifested and evaluated; and (3) the complete absence of neurological activity
      of gadobenate dimeglumine shows its safety profile and confirms its suitability
      for use in neurological diseases for which contrast-enhanced magnetic resonance
      imaging is indicated.

PMID- 11577268
TI  - Comparison of contrast-enhanced fundamental imaging, second-harmonic imaging, and
      pulse-inversion harmonic imaging.
AB  - RATIONALE AND OBJECTIVES: To investigate the feasibility of recent contrast
      specific ultrasound techniques in depicting vascular flow and the effects of
      changing the output power of the transducer and insonation mode on contrast
      enhancement, the authors performed an experimental study with a flow phantom.
      METHODS: While changing the mechanical index and the sound insonation mode
      (continuous and intermittent), images were obtained with three contrast-enhanced
      ultrasound techniques: fundamental, second-harmonic, and pulse-inversion harmonic
      imaging (PIHI) after a bolus injection of microbubble contrast agent. The images
      were compared on a time-intensity curve. RESULTS: In assessing fixed flow (10
      cm/s), PIHI showed the best depiction of flow signal. In intermittent scanning,
      increases in the mechanical index caused stronger flow signals and longer
      enhancement duration in all techniques. However, continuous scanning revealed
      poor depiction of flow signal regardless of the technique or changes in the
      mechanical index because of significant bubble destruction. CONCLUSIONS:
      Microbubble-enhanced PIHI with intermittent scanning at a high mechanical index
      can depict vascular flow highly effectively without shortening the duration of
      enhancement.

PMID- 11577269
TI  - Vascular response to gadolinium-containing contrast media in an ex vivo rabbit
      arterial model.
AB  - RATIONALE AND OBJECTIVES: To assess the influence of gadolinium-containing
      magnetic resonance contrast agents on contractility of the arterial vessel wall.
      METHODS: Bilateral segments of rabbit carotid arteries were mounted in flow
      chambers, surrounded by aerated (95% O2, 5% CO2) Krebs' solution, and perfused at
      a constant rate by separated and aerated Krebs' solution. Therefore, changes in
      pressure of the circulating Krebs' solution indicated alterations of vessel wall
      contractility. Viability of the artery was tested by 124 mmol/L KCl, 3 x 10-5
      mol/L phenylephrine, and 10-5 mol/L acetylcholine. After a washout phase,
      gadopentate (n = 10) or gadoteridol (n = 10) was added to the perfusate of one
      carotid artery in increments of 0.1, 0.3, and 0.6 mmol/L. Concentrations up to
      0.9 mmol/L and 1.2 mmol/L were tested, respectively. The contralateral artery
      served as a control. To assess potential relaxing effects of the media, vessels
      were brought into a contracted status with 3 x 10-5 mol/L phenylephrine and then
      received gadolinium chelates. RESULTS: Potassium chloride and phenylephrine
      increased and acetylcholine decreased the pressure, indicating vasoconstriction
      and vasodilatation, respectively. After gadopentate and gadoteridol infusion, no
      statistically significant pressure changes could be detected, ruling out any
      vasoconstrictor or vasodilator effect. CONCLUSIONS: Gadopentetate and gadoteridol
      in doses of up to 1.2 mmol/L did not alter vessel wall tone. The impact of
      contrast media on blood pressure, as has been shown in some clinical trials,
      probably is not due to direct changes in arterial wall tone.

PMID- 11577270
TI  - Human brain chemical shift imaging at age 60 to 90: analysis of the causes of the
      observed sex differences in brain metabolites.
AB  - RATIONALE AND OBJECTIVES: To assess whether differences in cerebral atrophy and
      white matter lesions or in the presence of lactate and lipid signals can explain
      the observed differences in brain choline, creatine, and N-acetylaspartate levels
      between healthy elderly women and men. METHODS: In addition to standard magnetic
      resonance imaging of the brain, an 8 x 8 x 2-cm3 supraventricular transverse
      brain volume parallel to the canthomeatal line was examined by magnetic resonance
      spectroscopy (automated 1H chemical shift imaging) in 540 healthy elderly
      persons. RESULTS: At P = 0.01, 0.001, and 0.0001, choline differed between women
      and men in 14, 9, and 5 of 36 voxels, respectively. On correction for cerebral
      atrophy (more frequent in men than in women), white matter lesions (more frequent
      in women), and lactate and lipid (more frequent in women), the differences in
      choline were reduced to 13, 6, and 3. Sex differences for creatine and N
      acetylaspartate were similar but less numerous after correction. CONCLUSIONS:
      Elderly women and men in the general population show differences in the levels of
      creatine, N-acetylaspartate, and especially choline in portions of the brain. The
      sex-related differences in brain metabolite levels cannot be explained by
      differences in cerebral atrophy or other aging-related phenomena (white matter
      lesions, lactate, lipid).

PMID- 11577271
TI  - Individually adapted examination protocols for reduction of radiation exposure in
      chest CT.
AB  - RATIONALE AND OBJECTIVES: To develop a simple directive for the reduction of
      radiation exposure without loss of diagnostic information in routine chest CT
      examinations. METHODS: Two hundred fifty adult patients (164 male, 86 female)
      were entered into a prospective trial. All examinations were performed with a
      multislice CT technique (Somatom Volume Zoom, Siemens). Four groups of 50
      patients each were scanned with patient-related specific parameters: individual
      mA-s values were derived from the estimated body weight: kilograms + 10, +/- 0, -
      10, and - 20 mAs. The results were compared with those of 50 patients who were
      examined by a standard chest protocol by using the parameters 120 mAs and 140 kV.
      All other parameters including the tube voltage were kept constant. Subjective
      image quality was rated on a three-point scale: 1 = excellent, 2 = fair, 3 =
      nondiagnostic. In addition, objective criteria based on signal-to-noise
      measurements were assessed by using a region-of-interest methodology. RESULTS:
      Image quality was sufficient in all cases. Mean subjective gradings of image
      quality, based on soft-tissue window settings, were 1.1 for the 120-mAs protocol,
      1.1 for the (body weight [kg] + 10) mAs protocol, 1.1 for the (body weight [kg]
      +/- 0) mAs protocol, 1.3 for the (body weight [kg] - 10) mAs protocol, and 1.2
      for the (body weight [kg] - 20) mAs protocol. Objective criteria based on noise
      measurements showed mean +/- standard deviation values of 5.7 +/- 0.8 Hounsfield
      units (HU) for the 120-mAs protocol. For the reduced-dose protocols, values were
      calculated as 7.6 +/- 1.2 HU (group + 10), 7.9 +/- 1.3 HU (group +/- 0), 8.7 +/-
      1.2 HU (group - 10), and finally 9.1 +/- 1.3 HU (group - 20). The best
      correlation for an entire subgroup was achieved with the - 10 protocol (body
      weight [kg] - 10) mAs, with nearly constant noise related to body weight in all
      patients. CONCLUSIONS: By deriving mAs values from body weight estimation, an
      individually adapted protocol for chest CT can be recommended and easily employed
      in a clinical setting. With an adaptation of the tube current-time product based
      on the estimated body weight of the patient - 10 (body weight [kg] - 10 mAs), a
      well-balanced examination without significant loss of information, even in soft
      tissue window settings, can be performed with this particular scanner. For this
      adapted mAs protocol, a mean reduction of radiation exposure of 45% was
      achievable, compared with the standard protocol. A maximum decrease per case down
      to 31 mAs was obtained, without relevant loss of image quality. Therefore, for
      other types of CT scanners, analogous protocols may be adapted.

PMID- 11577272
TI  - Assessment of the position of the distal portion of the ulna in lateral
      projection radiographs of the wrist: analysis of the influence of pronation
      supination and flexion-extension on the pisoscaphoid and the ulnotriquetral
      distances: a cadaver study.
AB  - RATIONALE AND OBJECTIVES: Accurate assessment of the distal radioulnar joint is
      of paramount importance for the detection of possible dislocation or subluxation.
      Using a cadaveric model, the authors attempted to establish a quantitative method
      that would allow identification of normal and abnormal distal radioulnar joint
      anatomy on well-positioned and rotated conventional radiographs. METHODS: Four
      cadaveric wrists, in which subsequent sectioning confirmed the absence of
      disease, and one cadaveric wrist with a circumscribed lesion of the triangular
      fibrocartilaginous complex were studied. Defined movements in flexion and
      extension (+/- 10 degrees, 20 degrees, 30 degrees ) and in pronation and
      supination (+/- 10 degrees, 20 degrees, 30 degrees ) as well as combined
      flexion/extension and pronation/supination were performed. The ulnotriquetral and
      the pisoscaphoid distances were assessed in each position. Correlation with
      cryosections was achieved. RESULTS: A strong linear correlation between the
      degree of pronation or supination and the pisoscaphoid and ulnotriquetral
      distances was noted. Flexion and extension produced no significant effect on the
      pisoscaphoid distance, but a defined shift of the ulnotriquetral distance
      occurred with increasing flexion and extension. CONCLUSIONS: If all parameters
      are taken into account, this correlation aids in estimating the degree of
      possible malpositioning of the wrist during radiography and the degree of
      subluxation of the distal radioulnar joint. Tabular data with parameters to
      correct for instances of malrotated images and to estimate the extent of
      dislocation or malrotation of the distal radioulnar joint are provided.

PMID- 11577273
TI  - Bile-tagged 3d magnetic resonance colonography after exclusive intravenous
      administration of gadobenate dimeglumine, a contrast agent with partial
      hepatobiliary excretion.
AB  - RATIONALE AND OBJECTIVES: Imaging of the colon is an important diagnostic
      procedure. Endoscopic colonoscopy and x-ray barium enemas are currently the
      standard diagnostic procedures. Magnetic resonance (MR) and computed tomographic
      colonography have been recently introduced with true three-dimensional (3D) cross
      sectional imaging. Up to now, all imaging techniques have required the use of
      oral and/or aboral contrast agents for luminal enhancement and commonly, a
      relaxation medication (glucagon or N-butylscopolamine). While performing several
      phase I, II, and III studies with a new partially hepatobiliary excreted
      gadolinium-based MR contrast agent, we noted substantial intraluminal enhancement
      within the colon and investigated its potential for imaging. METHODS: Three
      dimensional MR angiographic techniques enable imaging of large volumes. We have
      used these sequences to detect contrast enhancement within the hepatobiliary and
      gastrointestinal systems. A 3D volume of 40 x 32 x 12 cm with 42 images was
      acquired under breath-hold. Six volunteers were studied according to the
      protocol. No bowel preparation was performed and no medication given. Subsequent
      follow-ups of the abdomen were performed at 1, 12, 24, 36, 48, 70, and 105 hours
      postinjection. Gadobenate dimeglumine at 0.1 mmol/kg body weight was given
      intravenously. Images were assessed quantitatively and by blinded reader
      analysis. RESULTS: Intense intraluminal contrast enhancement within the colon was
      seen within 24 hours in all subjects. The homogeneous enhancement was of
      sufficient intensity to enable 3D visualization and virtual endoscopy. The
      optimal time window for imaging was determined to be 16 to 50 hours
      postinjection. CONCLUSIONS: We report for the first time the feasibility of
      exclusively bile-tagged MR colonography with the use of only an intravenous MR
      contrast that exhibits partial hepatobiliary excretion. This new diagnostic
      procedure will enable not only morphological assessment of the colon but also
      functional and pathophysiological studies on the transport kinetics of bile and
      stool without any preparation of the patient.

PMID- 11577274
TI  - Emergency nursing around the world.

PMID- 11577275
TI  - If infection control practitioners could say one thing to emergency nurses, what
      would it be?

PMID- 11577276
TI  - Infectious disease--an insidious killer.

PMID- 11577277
TI  - Giving lock of hair to deceased ED patients' families lauded.

PMID- 11577278
TI  - Emergency nursing publications challenged to include end-of-life care content.

PMID- 11577279
TI  - Increase salaries to attract more nurses.

PMID- 11577282
TI  - The importance of quickly initiating antibiotic therapy in a 20-year-old man with
      bacterial meningitis.

PMID- 11577283
TI  - Management of bloodborne fluid exposures with a rapid treatment prophylactic
      caremap: one hospital's 4-year experience.

PMID- 11577284
TI  - Blood exposure--remember the emotional side.

PMID- 11577285
TI  - The role of emergency nurses in the prevention and control of influenza and
      pneumococcal disease.

PMID- 11577286
TI  - Lyme disease: an in-depth look at a formidable infection.

PMID- 11577287
TI  - Responding to the threat of bioterrorism: practical resources and references, and
      the importance of preparation.

PMID- 11577289
TI  - Emergency care during the 1999 World Trade Organization meeting in Seattle.

PMID- 11577290
TI  - How do you isolate contagious patients in the emergency department?

PMID- 11577291
TI  - Something special in the air: American Airlines adds SKYCAARE for RN-assisted
      travel.

PMID- 11577292
TI  - An overview of a few well-known national children's gun safety programs and ENA's
      newly developed program.

PMID- 11577293
TI  - Nurses welcome standards provided by new needlestick law.

PMID- 11577295
TI  - An effective, fun annual emergency competency day/skills fair: St John's 2-year
      experience.

PMID- 11577296
TI  - Pediatric liaison nurses of LA county representing 55 emergency departments
      celebrate 15th anniversary.

PMID- 11577297
TI  - A look at travel nursing: two sides to the coin.

PMID- 11577298
TI  - HIV prophylaxis within a treatment protocol for sexual assault victims: rationale
      for the decision.

PMID- 11577299
TI  - Use of the personal digital assistant for point-of-care trauma documentation.

PMID- 11577300
TI  - A woman with unilateral eye pain and malaise.

PMID- 11577302
TI  - Risk factors for post-ERCP pancreatitis: a prospective, multicenter study.
AB  - BACKGROUND: Post-ERCP pancreatitis is poorly understood. The goal of this study
      was to comprehensively evaluate potential procedure- and patient-related risk
      factors for post-ERCP pancreatitis over a wide spectrum of centers. METHODS:
      Consecutive ERCP procedures were prospectively studied at 11 centers (6 private,
      5 university). Complications were assessed at 30 days by using established
      consensus criteria. RESULTS: Pancreatitis occurred after 131 (6.7%) of 1963
      consecutive ERCP procedures (mild 70, moderate 55, severe 6). By univariate
      analysis, 23 of 32 investigated variables were significant. Multivariate risk
      factors with adjusted odds ratios (OR) were prior ERCP-induced pancreatitis (OR
      5.4), suspected sphincter of Oddi dysfunction (OR 2.6), female gender (OR 2.5),
      normal serum bilirubin (OR 1.9), absence of chronic pancreatitis (OR 1.9),
      biliary sphincter balloon dilation (OR 4.5), difficult cannulation (OR 3.4),
      pancreatic sphincterotomy (OR 3.1), and 1 or more injections of contrast into the
      pancreatic duct (OR 2.7). Small bile duct diameter, sphincter of Oddi manometry,
      biliary sphincterotomy, and lower ERCP case volume were not multivariate risk
      factors for pancreatitis, although endoscopists performing on average more than 2
      ERCPs per week had significantly greater success at bile duct cannulation (96.5%
      versus 91.5%, p = 0.0001). Combinations of patient characteristics including
      female gender, normal serum bilirubin, recurrent abdominal pain, and previous
      post-ERCP pancreatitis placed patients at increasingly higher risk of
      pancreatitis, regardless of whether ERCP was diagnostic, manometric, or
      therapeutic. CONCLUSIONS: Patient-related factors are as important as procedure
      related factors in determining risk for post-ERCP pancreatitis. These data
      emphasize the importance of careful patient selection as well as choice of
      technique in the avoidance of post-ERCP pancreatitis.

PMID- 11577303
TI  - Serum lipase, C-reactive protein, and interleukin-6 levels in ERCP-induced
      pancreatitis.
AB  - BACKGROUND: C-reactive protein (CRP) and interleukin-6 (IL-6) are elevated in
      acute pancreatitis. Limited studies have evaluated their role in ERCP-induced
      pancreatitis. The aim of this study was to assess the role of serum lipase, CRP,
      and IL-6 in ERCP-induced pancreatitis. METHODS: Eighty-five patients (62 women,
      23 men; mean age 43 years; range 16-85 years) who underwent ERCP were entered in
      a prospective trial. ERCP-induced pancreatitis was classified as mild, moderate,
      or severe. Serum levels of lipase, CRP, and IL-6 were measured before ERCP and at
      12 to 24 hours and 36 to 48 hours after ERCP. RESULTS: Mild, moderate, and severe
      pancreatitis occurred, respectively, in 9, 7, and 4 patients after ERCP. There
      were significant differences in levels of CRP and IL-6 but not lipase for
      patients with mild versus moderate and moderate versus severe pancreatitis. The
      mean CRP levels (mg/dL) at 12 to 24 hours were 0.98 +/- 0.24 in mild
      pancreatitis, 3.89 +/- 0.32 in moderate pancreatitis, and 12.0 +/- 1.60 in severe
      pancreatitis. The levels, respectively, at 36 to 48 hours were 1.60 +/- 0.31,
      7.60 +/- 0.74, and 25.0 +/- 2.9. The mean IL-6 levels (pg/mL) at 12 to 24 hours
      were 16.6 +/- 2.06 in mild pancreatitis, 73.0 +/- 15.60 in moderate pancreatitis,
      and 235.5 +/- 26.31 in severe pancreatitis. The levels at 36 to 48 hours were,
      respectively, 18.92 +/- 3.28, 100.17 +/- 11.56, and 438.2 +/- 71.50. CONCLUSIONS:
      Serum CRP and IL-6 levels may be useful early markers for predicting the severity
      of ERCP-induced pancreatitis.

PMID- 11577304
TI  - Randomized controlled trial of EUS-guided fine needle aspiration techniques for
      the detection of malignant lymphadenopathy.
AB  - BACKGROUND: EUS-guided fine needle aspiration (EUS-FNA) is a highly accurate
      method of detecting malignant lymphadenopathy. The optimal methods for performing
      EUS-FNA to maximize sensitivity and to minimize the number of needle passes
      necessary are unknown. This is a report of the results of a prospective
      randomized controlled trial to determine the effect of suction, the site of FNA
      (edge or center of lymph node), and the method of preparation of cytologic
      specimens on accuracy, number of needle passes needed, and specimen quality.
      METHODS: Consecutive patients with lymphadenopathy detected by EUS underwent FNA.
      Each lymph node was sampled with or without suction and from the edge or center
      in a 2 x 2 factorial design. The samples were expressed onto slides for cytology,
      and the residual material in the needle was analyzed by the cytospin-cellblock
      technique. Each aspirate was individually characterized for a diagnosis of
      malignancy, cellularity, and bloodiness. RESULTS: Forty-three patients with a
      total of 46 lymph nodes were evaluated. The final lymph node diagnosis was benign
      in 22 (48%), "suspicious for malignancy" in 6 (13%), and malignant in 18 (39%).
      The use of suction was associated with an increase in the cellularity of the
      specimen, but did not improve the likelihood of obtaining a correct diagnosis (OR
      1.52: 95% CI [0.81, 2.85]). Samples obtained with suction were of worse quality
      because of excessive bloodiness (OR 4.7: 95% CI [1.99, 11.24]). Aspiration from
      the edge of the lymph node (compared with the center) did not increase the
      likelihood of a correct diagnosis (OR 1.16: 95% CI [0.42, 3.21]). For 78% of
      malignant lymph nodes, the correct diagnosis was obtained on the first needle
      pass and for 100% by the third pass. Cytospin-cellblock methods did not add any
      additional diagnostic information compared with direct smear cytology.
      CONCLUSIONS: The traditional method of applying suction during EUS-FNA does not
      improve diagnostic accuracy and worsens specimen bloodiness compared with FNA
      without suction. The site of FNA within the lymph node does not affect accuracy.
      When EUS-FNA is necessary, our recommendation is up to 3 FNAs without suction
      from the most convenient and safe location within abnormal-appearing lymph nodes.

PMID- 11577305
TI  - Duodenal erosions after eradication of Helicobacter pylori infection.
AB  - BACKGROUND: There is interest in the development of GERD after Helicobacter
      pylori eradication. In contrast, the development of duodenal erosions after
      therapy has received scant attention. Patients were examined after eradication of
      H pylori infection to determine the frequency of post-therapy duodenal erosions
      (primary outcome) and whether there was a relation between development of
      duodenal and esophageal erosions. Additionally, factors were searched for that
      would identify patients at increased risk for duodenal erosions. METHODS: A
      single-center, endoscopist-blinded, observational study was conducted of 196
      patients in whom H pylori was eradicated. The presence of esophageal or duodenal
      erosions was evaluated 4 weeks and 6 months after eradication. Serum gastrin and
      pepsinogen I (PG I) and II (PG II) levels were also determined for 83 patients
      entering the study during its final year. RESULTS: Multiple small duodenal
      erosions developed in 8.6% of patients after H pylori eradication and were more
      common in patients with pre-eradication duodenal ulcer (27.8%) compared with
      those with gastric ulcer (6.7%) or atrophic gastritis (1.4%) (p < 0.05). Duodenal
      erosions were associated with high levels of PG I before and after eradication.
      The frequency of duodenal erosions decreased over time (3.1% by 6 months).
      CONCLUSION: Duodenal erosions occur after H pylori eradication and appear to be
      related to duodenal ulcer and increased PG I levels, both of which are associated
      with increased acid secretion. Measurement of PG I may help to identify patients
      who have duodenal erosions develop after H pylori therapy for studies of the
      pathogenesis of these lesions.

PMID- 11577306
TI  - Incidence of gastroesophageal malignancy in patients with dyspepsia in Hong Kong:
      implications for screening strategies.
AB  - BACKGROUND: A "test-and-treat" strategy for H pylori infection has been
      recommended in Europe and North America as safe and cost-effective for management
      of patients with dyspepsia. The primary aim of this study was to determine the
      frequency of gastroesophageal cancer in 2 groups of patients with dyspepsia:
      those 45 years of age or younger without "alarm" symptoms (low-risk group) and
      patients over 45 years of age or any patient with "alarm" symptoms (high-risk
      group). A secondary aim was to determine the frequency of gastric cancer among
      patients in the low-risk group with or without a positive serology for H pylori.
      METHODS: Patients with persistent dyspepsia were recruited from 4 regional
      hospitals in Hong Kong. Those in the low-risk group were evaluated for H pylori
      by using a whole blood serology test; they underwent endoscopy within 1 week.
      Those in the high-risk group and those taking nonsteroidal anti-inflammatory
      drugs (NSAIDs) underwent endoscopy promptly. Alarm symptoms were as follows:
      weight loss (10 or more pounds over 8 weeks), recurrent vomiting, dysphagia,
      bleeding, or anemia. RESULTS: Of 2627 patients enrolled, 1017 were in the low
      risk group and 1610 in the high-risk group. Twenty-three patients (0.9%) had
      gastroesophageal cancers (20 gastric, 3 esophageal). Four patients with cancer
      (17.4%) were in the low-risk group (3 gastric, 1 esophageal); all except the
      patient with esophageal cancer had a positive serology test. In the high-risk
      group, 19 patients had cancer (17 gastric, 2 esophageal). CONCLUSION: Gastric
      cancer is relatively frequent among young patients with dyspepsia who have no
      alarm features in Hong Kong. This finding raises concerns as to the safety of the
      "test-and-treat" strategy for the management of patients with dyspepsia in Asia.

PMID- 11577307
TI  - Medium-term effects of endoscopic papillary balloon dilation on gallbladder
      motility.
AB  - BACKGROUND: Endoscopic papillary balloon dilation (EPBD) for removal of bile duct
      stones tends to preserve papillary function. However, EPBD may exert beneficial
      or deleterious effects on gallbladder motility. This was a prospective, medium
      term investigation (2 years) of the effects of EPBD on gallbladder motility.
      METHODS: Twelve patients with intact gallbladders (6 with and 6 without
      gallbladder stones) who underwent EPBD for choledocholithiasis were enrolled in
      this study. Gallbladder motility was examined before EPBD and at 7 days, 1 month,
      1 year, and 2 years after EPBD. Gallbladder volumes, measured after fasting and
      after ingestion of dried egg yolk, were determined by US. RESULTS: All patients
      were asymptomatic during the 2-year follow-up period. Before EPBD, particularly
      in patients with cholelithiasis, the gallbladder had a larger fasting volume and
      lower yolk-stimulated maximum contraction compared with normal control subjects.
      Seven days after EPBD, fasting volume was decreased and maximum contraction was
      increased, both significantly compared with pre-EPBD values and regardless of the
      presence or absence of gallbladder stones. At 1 month, 1 year, and 2 years after
      EPBD, these changes were far less evident and gallbladder function did not differ
      significantly from baseline. CONCLUSION: EPBD does not adversely affect
      gallbladder motility in the medium-term (2 years). In terms of gallbladder
      motility, EPBD does not appear to increase the future risk of acute cholecystitis
      or gallbladder stone formation.

PMID- 11577308
TI  - Clinical characteristics of double pylorus.
AB  - BACKGROUND: Double pylorus can occur as either a congenital abnormality or an
      acquired complication of peptic ulcer disease. There has been no report of long
      term follow-up of a large series of patients treated for double pylorus. The
      objective of this study was to determine the course of double pylorus in 20
      patients by serial endoscopic examination. METHODS: Among 102,958 endoscopic
      examinations conducted from 1987 to 1999, a diagnosis of double pylorus was made
      in 20 patients, 18 of whom were followed from 2 months to 10 years. The
      demographics, clinical presentations, and outcome, as well as endoscopic patterns
      of double pylorus, were retrospectively reviewed. The rates of ulcer recurrence
      and symptoms were estimated and compared. RESULTS: Most fistulous rings were
      located on the lesser curve of the gastric antrum (75%). Evolution from an
      original ulcer to fistula was observed in 9 patients. The fistula disappeared in
      1 patient, remained open in 12, and converged with the normal pyloric ring in 5
      patients. One or more associated systemic diseases and extensive treatment with
      various drugs were noted in 12 patients. Eradication of Helicobacter pylori in
      infected patients resulted in a lower percentage of patients with symptoms (36%
      vs. 100%) and ulcer recurrence (55% vs. 100%) compared with uninfected patients,
      but the differences were not statistically significant. CONCLUSION: In this
      study, fistula closure did not occur in the majority of patients. Associated
      systemic diseases and extensive use of medications might be important factors in
      persistence of double pylorus. Eradication of Helicobacter pylori was not
      beneficial in terms of relief of symptoms, prevention of ulcer recurrence, and
      fistula closure. Surgical intervention should be considered for patients with
      refractory symptoms, recurrent ulcers, and other complications.

PMID- 11577309
TI  - Endoscopic treatment of post-liver transplantation biliary leaks with stent
      placement across the leak site.
AB  - BACKGROUND: Biliary tract leaks occur in over 10% of patients undergoing liver
      transplantation and are the most common cause of biliary tract-related death in
      these patients. A number of treatment options are available, but a standard
      approach has not been established. METHODS: Twenty-six patients were
      retrospectively studied who had post-transplantation leaks develop with special
      reference to those who underwent endoscopic placement of a "leak-bridging" stent.
      RESULTS: Endoscopic retrograde cholangiography was performed in all cases with no
      procedure-related complications. Twenty-four patients had a leak-bridging stent,
      1 a transpapillary stent, and 1 a nasobiliary drain. Leak resolution occurred in
      23 cases (88%) after initial stent placement. The median time to stent removal
      was 8 weeks. Three patients did not respond to initial treatment; 2 were
      successfully treated with another stent and a single patient required surgical
      repair. Four deaths occurred during follow-up, all unrelated to the biliary leak.
      CONCLUSIONS: Placement of a leak-bridging stent is a safe and effective initial
      treatment for post-liver transplantation biliary leaks.

PMID- 11577310
TI  - Laparoscopic adhesiolysis for recurrent small bowel obstruction: long-term follow
      up.
AB  - BACKGROUND: Recurrent small bowel obstruction caused by postoperative adhesions
      has traditionally been treated by conventional laparotomy, but laparoscopic
      management of acute small bowel obstruction has been reported. The aim of this
      study was to assess the long-term efficacy and clinical outcome of laparoscopic
      adhesiolysis for recurrent small bowel obstruction. METHODS: After conservative
      treatment, elective laparoscopic treatment was attempted in 17 patients
      hospitalized for recurrent small bowel obstruction after abdominal or pelvic
      surgery. RESULTS: Postoperative adhesions were identified laparoscopically in all
      patients. Laparoscopic treatment was possible in 14 patients (82.4%). Conversion
      to laparotomy was required for 3 patients (17.6%) because of intestinal
      perforation (n = 1) or a convoluted mass of adherent bowel (n = 2). Long-term
      follow-up was possible in 16 patients. Two recurrences of small bowel
      obstructions were noted over a mean follow-up period of 61.7 months. CONCLUSIONS:
      Laparoscopic adhesiolysis is a safe and effective treatment for recurrent small
      bowel obstruction. Conversion to laparotomy should be considered in patients with
      dense adhesions.

PMID- 11577311
TI  - Benign esophageal strictures in infants and children: results of Savary-Gilliard
      bougie dilation in 107 Indian children.
AB  - BACKGROUND: Little information is available regarding the safety and efficacy of
      dilation of esophageal strictures in children with Savary-Gilliard bougies. This
      is a report of our experience with this form of dilation in Indian children.
      METHODS: One hundred seven Indian children age 14 years or younger with benign
      esophageal strictures underwent dilation. Clinical information including etiology
      was recorded. Dilation was performed at 2- to 3-week intervals by using Savary
      Gilliard bougies under ketamine sedation and was considered adequate if the
      esophageal lumen could be dilated to 15 mm diameter (12.8 mm in children <5 years
      of age) with complete relief of symptoms. Subsequently, dilation was performed on
      an "as needed" basis. RESULTS: Mean age was 4.8 +/- 3.4 years; male to female
      ratio was 3:1. Fifty-four children had corrosive strictures (acid 34, alkali 20).
      Noncorrosive strictures were sclerotherapy-induced (23), postsurgical (14),
      congenital (10), peptic (4), and due to other causes (2). Dilation was successful
      in all but 3 cases. Corrosive strictures required a significantly higher number
      of sessions to achieve adequate initial dilation (2.4 +/- 1.9 vs. 1.3 +/- 0.5, p
      < 0.01). Patients with corrosive strictures also required a higher number of
      subsequent sessions for recurrence (7.3 +/- 6.5 vs. 0.7 +/- 1.3, p = 0.10).
      Dilation was also successful in patients with strictures 5 cm or more in length
      and/or patients with multiple corrosive strictures, although these required a
      higher number of sessions to achieve adequate dilation (p < 0.05) and also higher
      number of subsequent sessions for recurrence. Six esophageal perforations
      occurred during 648 dilation sessions (0.9%); 5 occurred in patients with
      corrosive strictures. One patient required surgery. CONCLUSIONS: Corrosive injury
      is the most common cause of benign esophageal strictures in Indian children.
      Savary-Gilliard bougie dilation is safe and effective, even for long and/or
      multiple corrosive strictures.

PMID- 11577312
TI  - Interactive role of the cytopathologist in EUS-guided fine needle aspiration: an
      efficient approach.

PMID- 11577313
TI  - Multiple lymphangiomas of the small intestine.

PMID- 11577315
TI  - Ileal vasculitis in Henoch-Schonlein purpura.

PMID- 11577314
TI  - Multiple lymphomatous polyposis.

PMID- 11577316
TI  - Broken T-tube branch causing bile duct stone.

PMID- 11577317
TI  - Gastric wall elasticity assessed by dynamic holographic endoscopy: ex vivo
      investigations in the porcine stomach.
AB  - BACKGROUND: Holographic interferometry is based on the superimposition of the
      holograms of different motional states of an object on a single holographic
      storage medium. It has been used to detect structural changes in prosthetic heart
      valves. The combination of holographic interferometry and endoscopic imaging were
      applied to assess disturbances of porcine stomach wall elasticity. METHODS: By
      connecting an electronic speckle pattern interferometry (ESPI) camera system
      (light source: continuous wave argon-ion laser, lambda = 514.5 nm) to different
      types of endoscopes, ex vivo experiments were performed on porcine stomachs to
      detect areas characterized by altered tissue elasticity. With linkage of the
      endoscopic ESPI camera complex to a fast image processing system, the method of
      double pulse exposure image subtraction was applied at a video frame rate of 12.5
      Hz. RESULTS: The speckle correlation patterns resulting from gentle gastric wall
      deformation were analyzed in a series of experiments in 16 porcine stomachs.
      Interferograms of gastric wall areas without structural abnormalities exhibited
      concentric fringes, whereas fringe patterns corresponding to areas of reduced
      tissue elasticity were characterized by parallel lines. CONCLUSION: Applying the
      nondestructive method of dynamic holographic endoscopy, abnormalities of the
      gastric wall leading to diminished tissue elasticity can be distinguished
      reliably from surrounding healthy tissue.

PMID- 11577318
TI  - Experimental endoscopic repair of gastric perforations with an omental patch and
      clips.
AB  - BACKGROUND: The omental patch is a standard surgical treatment of gastroduodenal
      ulcer perforation. This is a report of an experimental method for endoscopic
      repair of anterior gastric perforations with an omental patch developed by using
      a porcine model. METHODS: A standardized gastric perforation was created in 10
      pigs. The omentum was pulled into the gastric lumen and fixed endoscopically to
      the muscularis propria layer of the stomach with metallic clips. RESULTS: The
      postoperative course was normal in 9 animals. An ulcer was evident at the site of
      repair at follow-up endoscopy. At autopsy, the omentum was adherent to the
      external side of gastric wall. One animal died with peritonitis, presumably
      because the muscularis propria layer could not be seen during the procedure, and
      the clips attached the omentum only to the mucosa. CONCLUSIONS: Endoscopic repair
      with an omental patch appears to be an effective procedure for closure of gastric
      perforations.

PMID- 11577319
TI  - Polyp retrieval after colonoscopic polypectomy: use of the Roth Retrieval Net.
AB  - BACKGROUND: All colon polyps removed during colonoscopy should be recovered and
      submitted for histopathologic analysis. Published information is scant regarding
      techniques and devices for retrieval of polyps after polypectomy. The Roth
      Retrieval Net is a novel device that has been used to retrieve foreign bodies
      from the GI tract, but its use as a polyp retrieval device has not previously
      been described. METHODS: A chart review was conducted over a 7-month period by
      one gastroenterologist in an office setting of all patients who had polyps
      retrieved after piecemeal polypectomy by using the Roth Retrieval Net. RESULTS:
      All resected polyps were completely retrieved in a time-efficient manner.
      Histopathologic evaluation was not compromised by the use of this device.
      CONCLUSIONS: The Roth Retrieval Net is well suited for retrieval of multiple
      polyp fragments after colonoscopic polypectomy.

PMID- 11577320
TI  - Treatment of complications of hepatic hydatid disease by ERCP.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of endoscopic
      sphincterotomy for preoperative and postoperative complications of hepatic
      hydatid disease. METHODS: Nineteen patients underwent endoscopic treatment for
      complications of hepatic hydatid disease. Indications for ERCP in 5 patients
      treated before surgery (Group A) were obstructive jaundice in 1 and acute
      cholangitis in 4. In 14 patients treated after surgery (Group B), the indication
      was acute cholangitis in 6, obstructive jaundice 2, and persistent external
      drainage in 6 patients. OBSERVATIONS: In group A, ERCP detected hydatid vesicles
      within the bile duct. All patients underwent endoscopic sphincterotomy and
      clearance of the duct with no complications. The 6 patients in Group B with
      persistent external drainage had biliary fistulas that resolved after endoscopic
      treatment within 10 to 20 days. Among the 8 patients with postoperative
      obstructive jaundice or acute cholangitis, 7 had cyst remnants obstructing the
      bile duct and 1 had findings of sclerosing cholangitis. All underwent endoscopic
      sphincterotomy and clearance of the bile duct without complications. After
      treatment, all patients, with the exception of the one with sclerosing
      cholangitis, remained asymptomatic. CONCLUSION: Endoscopic sphincterotomy is a
      safe and effective treatment for biliary complications of hepatic hydatid
      disease.

PMID- 11577321
TI  - The rendezvous technique for the treatment of choledocholithiasis.
AB  - BACKGROUND: The rendezvous technique combines endoscopy with percutaneous
      transhepatic cholangiography to facilitate cannulation of the bile duct when
      previous attempts have failed. METHODS: Over a 7-year period, a total of 1753
      ERCPs were performed. Twelve of these patients with a diagnosis of
      choledocholithiasis were poor candidates for surgery. Percutaneous transhepatic
      cholangiography as well as ERCP with precut papillotomy failed to resolve biliary
      obstruction. In a further 2 cases the percutaneous approach was used by means of
      a T-tube positioned at a prior cholecystectomy. OBSERVATIONS: The combined
      procedure was successful in 13 patients (93%). It was unsuccessful in 1 patient
      because of a stone lodged distally near the papilla. There was only 1
      complication (7%), a retroperitoneal perforation that occurred during
      papillotomy; no mortality was directly attributable to the technique.
      CONCLUSIONS: The rendezvous technique is recommended for patients who are not
      eligible for surgery when ERCP is unsuccessful and when it is impossible to
      resolve biliary obstruction by percutaneous transhepatic cholangiography.

PMID- 11577322
TI  - Esophageal squamous cell carcinoma with lymphoid stroma: report of 3 cases with
      immunohistochemical analyses.

PMID- 11577323
TI  - Colonic infiltration associated with myelodysplastic syndrome.

PMID- 11577324
TI  - Esophageal schwannoma: first report of successful management by endoscopic
      removal.

PMID- 11577325
TI  - A novel technique for endoscopic removal of a migrated colonic stent.

PMID- 11577326
TI  - Rendu-Osler-Weber disease successfully treated by argon plasma coagulation.

PMID- 11577327
TI  - Gastric outlet obstruction secondary to heterotopic pancreas in the antrum: case
      report and review.

PMID- 11577328
TI  - Systemic mastocytosis and giant gastroduodenal ulcer.

PMID- 11577329
TI  - Endoscopic dilation of an ileocolonic stricture in an infant with short gut
      syndrome.

PMID- 11577330
TI  - ERCP is most dangerous for people who need it least.

PMID- 11577332
TI  - Overall publication rates.

PMID- 11577331
TI  - The current status of the treatment of common bile duct stones in Brazil: a plea
      for communication.

PMID- 11577333
TI  - A concern with use of the "push technique" in patients with multiple esophageal
      rings.

PMID- 11577334
TI  - Why are significant (older) studies omitted from "new" reports? Cholangitis, a
      case in point.

PMID- 11577335
TI  - Helicobacter pylori and duodenogastric reflux.

PMID- 11577336
TI  - The analysis of clinical studies: the analysis of count data, part I.

PMID- 11577338
TI  - More about peer review: is it time for double-blind reviews?

PMID- 11577339
TI  - The end of immunology?

PMID- 11577340
TI  - Beating a kinase?

PMID- 11577341
TI  - Can we apply the TH1-TH2 paradigm to all lymphocytes?

PMID- 11577342
TI  - Redirecting T cell specificity by TCR gene transfer.

PMID- 11577343
TI  - Hypermutation: give us a break.

PMID- 11577344
TI  - The T cell receptor SLAPs integrins together.

PMID- 11577346
TI  - Nitric oxide and the immune response.
AB  - During the past two decades, nitric oxide (NO) has been recognized as one of the
      most versatile players in the immune system. It is involved in the pathogenesis
      and control of infectious diseases, tumors, autoimmune processes and chronic
      degenerative diseases. Because of its variety of reaction partners (DNA,
      proteins, low-molecular weight thiols, prosthetic groups, reactive oxygen
      intermediates), its widespread production (by three different NO synthases (NOS)
      and the fact that its activity is strongly influenced by its concentration, NO
      continues to surprise and perplex immunologists. Today, there is no simple,
      uniform picture of the function of NO in the immune system. Protective and toxic
      effects of NO are frequently seen in parallel. Its striking inter- and
      intracellular signaling capacity makes it extremely difficult to predict the
      effect of NOS inhibitors and NO donors, which still hampers therapeutic
      applications.

PMID- 11577347
TI  - Final steps of natural killer cell maturation: a model for type 1-type 2
      differentiation?
AB  - Analysis of cytokine and differentiation antigen expression in human natural
      killer (NK) cells revealed that interleukin 13 (IL-13) and interferon gamma (IFN
      gamma) are produced at sequential stages during irreversible IL-12-induced
      differentiation. In human NK cell clones, polyclonal CD3-CD161+CD56- cells and
      peripheral lymphocytes, IL-4 induced the proliferation of both IL-13+ NK and T
      cells, whereas IL-12 allowed a proliferation-independent accumulation of IFN
      gamma+ cells. These data disproved the NK1-NK2 hypothesis and challenge the
      current T helper 1 (TH1)-TH2 paradigm. We propose that the cytokine environment
      regulates a type 2-->0-->1 developmental progression, with IL-12 needed for
      terminal differentiation and IL-4 delaying this process, rather than a type 1
      versus type 2 decision of a type 0 cell.

PMID- 11577348
TI  - Direct inhibition of Bruton's tyrosine kinase by IBtk, a Btk-binding protein.
AB  - Bruton's tyrosine kinase (Btk) is required for human and mouse B cell
      development. Btk deficiency causes X-linked agammaglobulinemia (XLA) in humans
      and X-linked immunodeficiency in mice. Unlike Src proteins, Btk lacks a negative
      regulatory domain at the COOH terminus and may rely on cytoplasmic Btk-binding
      proteins to regulates its kinase activity by trans-inhibitor mechanisms.
      Consistent with this possibility, IBtk, which we identified as an inhibitor of
      Btk, bound to the PH domain of Btk. IBtk downregulated Btk kinase activity, Btk
      mediated calcium mobilization and nuclear factor-kappaB-driven transcription.
      These results define a potential mechanism for the regulation of Btk function in
      B cells.

PMID- 11577349
TI  - Immunotherapy through TCR gene transfer.
AB  - The antigen specificity of T lymphocytes is dictated solely by the T cell
      receptor (TCR) alpha and beta chains. Consequently, genetic transfer of TCR
      chains may be an appealing strategy with which to impose a desirable virus- or
      tumor-antigen specificity onto cytotoxic or helper T cell populations. We
      describe here the genetic introduction of a virus-specific TCR into peripheral T
      cells in a mouse model system. These experiments showed that T cells redirected
      by TCR gene transfer expanded upon viral infection of mice and efficiently homed
      to effector sites. In this setting, TCR gene transfer was not associated with any
      significant autoimmune pathology. In addition, small numbers of TCR-transduced T
      cells promoted the rejection of antigen-expressing tumors in vivo. These data
      suggest that the redirection of T cells by TCR gene transfer is a viable strategy
      for the rapid induction of virus- or tumor-specific immunity.

PMID- 11577352
TI  - [The relationship between cerebral blood flow (CBF) and the cerebral blood flow
      velocity (CBFV): Influence of halothane and cerebral CO2 reactivity].

PMID- 11577350
TI  - Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene
      transfer.
AB  - We identified a tumor-associated cytotoxic T lymphocyte (CTL) epitope derived
      from the widely expressed human MDM2 oncoprotein and were able to bypass self
      tolerance to this tumor antigen in HLA-A*0201 (A2.1) transgenic mice and by
      generating A2.1-negative, allo-A2.1-restricted human T lymphocytes. A broad range
      of malignant, as opposed to nontransformed cells, were killed by high-avidity
      transgenic mouse and allogeneic human CTLs specific for the A2.1-presented MDM2
      epitope. Whereas the self-A2.1-restricted human T cell repertoire gave rise only
      to low-avidity CTLs unable to recognize the natural MDM2 peptide, human A2.1+ T
      lymphocytes were turned into efficient MDM2-specific CTLs upon expression of wild
      type and partially humanized high-affinity T cell antigen receptor (TCR) genes
      derived from the transgenic mice. These results demonstrate that TCR gene
      transfer can be used to circumvent self-tolerance of autologous T lymphocytes to
      universal tumor antigens and thus provide the basis for a TCR gene transfer-based
      broad-spectrum immunotherapy of malignant disease.

PMID- 11577353
TI  - [Effects of dexamethasone on extravascular lung water and pulmonary haemodynamics
      in patients undergoing coronary artery bypass surgery].

PMID- 11577354
TI  - [Changes in the cytokine network through escalating SIRS after heart surgery].
AB  - Changes in the Cytokine Network Through Escalating SIRS After Heart Surgery.
      Cardiopulmonary bypass is associated with an injury that may cause
      pathophysiological changes in form of systemic inflammatory response syndrome
      (SIRS) or multiple organ dysfunction syndrome (MODS). There is a lot of
      information about the immunologic alterations in patients undergoing
      cardiopulmonary bypass, but only little is known about the expression of
      cytokines in patients with severe SIRS or MODS following cardiovascular surgery.
      In the present study, we investigated the inflammatory response of patients with
      an escalating SIRS following open heart surgery. Plasma levels of cytokines (IL
      1beta, IL-6, IL-8, IL-10, IL-12, IL-18, GM-CSF and TGF-beta) were measured at the
      first four postoperative days in 12 adult male patients with severe SIRS (SIRS
      group), and 15 patients with uncomplicated course (control-group) following
      myocardial revascularization. All cytokines (except IL-1beta) were significantly
      elevated in SIRS-patients, the analysis of differences between the survivors and
      non-survivors within the SIRS-group showed dramatically elevated levels of IL-8
      and IL-18 in non-survivors. From the results of our investigation we can conclude
      that monitoring of immunologic parameters, e.g. IL-8 and/or IL-18 may be helpful
      for the early detection and prognosis of high-risk patients with severe SIRS and
      MODS following cardiac surgery.

PMID- 11577355
TI  - [Measurement of water vapour pressure in the airways of mechanically ventilated
      patient using different types of humidifiers].
AB  - AIM OF THE INVESTIGATION: To evaluate the performance of different types of
      humidifying systems (heat and moisture exchanger, HME, and heated humidifier, HH)
      in the tracheo bronchial airway system of intubated mechanically ventilated
      patients. METHODS: A heated and fast responding capacitive sensor with a time
      constant of 0,23 s was used to measure the water vapor pressure at different
      locations in the tracheo bronchial airway system of 12 patients after therapeutic
      bronchoscopy. The sensor was immersed in an airstream of app. 1 ml/s continuously
      sampled with a bronchoscope in which the working pipe and the handle have been
      equipped with a heating system to prevent condensation. The sampling positions
      were 3 cm distal of the bifurcation in the right main bronchus, 2 cm proximal of
      the bifurcation and at the tube connector respectively. RESULTS: Without any
      humidifying system there was a dramatic reduction of the climatisation index
      respectively increase of the pulmonary water loss index, most prominently visible
      at the tube connector. There were significant differences between different types
      of HME (Pall BB 100 vs. Medisize Hygrovent S) but no significant differences
      between the Hygrovent S and the HH Fisher & Paykel 630 set at 34 degrees C. In
      consideration of applied tidalvolumens between 550 and 950 ml, isothermic
      saturation has not been reached in close vicinity to the bifurcation.
      CONCLUSIONS: HME may differ substantially from one type to the other and should
      not be used as climatisation system without careful consideration of their
      performance data. Effective HME are equivalent to HH at 34 degrees C and may
      therefore also be used for long term ventilation.

PMID- 11577356
TI  - [Attempted CPR in nursing homes - life-saving at the end of life?].
AB  - AIM: We studied the course and success rate of cardiopulmonary resuscitation
      (CPR) attempted on nursing home residents by a physician-staffed pre-hospital
      advanced cardiac life support (ACLS) team. METHODS: Ambulance records of nursing
      home residents from Goettingen/Germany who had a cardiac arrest were examined
      retrospectively. RESULTS: During a seven-year period (1992 - 1998) the ACLS team
      was called to 71 residents (mean age 81.8 years) who sustained cardiac arrest. In
      25 patients no CPR was attempted: 20 were pronounced dead by the arriving
      emergency physician, though only in 7 patients obvious clinical signs of death
      were present. Five patients suffered from a continuous deterioration of their
      health status and the ACLS team arrived after the process of dying had already
      started. No CPR attempt was initiated. The ACLS team performed CPR on 46 nursing
      home residents. In 33 patients (72 % of CPR attempts) no return of spontaneous
      circulation (ROSC) was achieved. In three patients (6%) palpable pulse returned
      only transiently. Ten patients (22 %) who showed ROSC were transported to the
      hospital. Six patients died within 24 hours after having been admitted to the
      hospital, two patients within the next 8 days. Two patients survived to hospital
      discharge. The first was a 79-year old woman who returned to the nursing home
      after three weeks and survived severely mentally disabled another five days. The
      second was an 83-year-old man who was hospitalised for 20 days, returned in a
      persistent vegetative state to the nursing home and died 10 months later. A
      comparison of the arrest characteristics demonstrated that in patients with
      successful CPR there was a higher incidence of a witnessed collapse, bystander
      CPR, ventricular fibrillation and cardiac aetiology of arrest. CONCLUSION: In a
      high rate (35 %) the ACLS team with the emergency physician at the scene withheld
      CPR efforts in nursing home residents. Even if CPR was initiated, the benefits
      were very limited with only two patients (4,3 %) surviving severely disabled to
      hospital discharge.

PMID- 11577357
TI  - [Bystander CPR - results and consequences from the Gottingen Pilot Project].

PMID- 11577358
TI  - [Treatment of chronic low back pain through intensive activation - an assessment
      of 10 years].
AB  - AIM OF THE STUDY: Treatment of chronic low back pain is a difficult problem and
      usually of low effectiveness. Aim of the study was to analyse the effectiveness
      of a multimodal treatment procedure. METHODS: From the basis of functional
      restoration concepts primarily established in the USA we conceptualized a
      treatment program which initially was funded by the German ministry of research.
      Over the years the regimen was modified in several respects (programs of
      different intensity). From 1990 to 2000 762 patients were treated in this way
      with one-year follow-up examination. RESULTS: Patients who were off work had
      significant differences in psychosocial and pain-related variables in comparison
      to those patients who were still working. Treatment procedures were in general
      very effective, although a modification of the program with less treatment (no
      work-hardening) failed in repeating the same effects. Pain intensity, disability,
      amount of depression and psychological distress improved significantly as well as
      work capability and use of the health care system. Nearly all results were seen
      to stabilize at the 12-month evaluation. DISCUSSION: Functional restoration
      programs for treatment of chronic low back pain have demonstrated effectiveness
      in several countries. By early use of these programs the high amount of costs due
      to back pain disability may be consequently reduced. Up to now in Germany these
      concepts are not well-known and insurance companies as well as the health system
      do not yet acknowledge them.

PMID- 11577360
TI  - [Importance of prevention of infectious complications in pediatric hematologic
      oncologic patients].
AB  - The control of severe infectious complications by preventive strategies, early
      diagnosis of infections and empiric broad-spectrum antibiotic therapy contributed
      to a marked improvement of survival in children with cancer over the last 20
      years. This article overviews of the importance of prevention of infectious
      complications in immunocompromised pediatric patients with hematologic or
      oncologic diseases. The particular challenge of this age group with respect to
      the acquisition and the spread of pathogens, the spectrum of causative
      microorganisms and the principal issues of anti-infectious prophylaxis are
      considered.

PMID- 11577361
TI  - [Non-pharmacologic strategies to prevent and control infectious complications in
      pediatric hematology/oncology patients].
AB  - Preventive strategies besides the use of prophylactic antibiotic or antifungal
      regimens are fundamental ingredients of infection control in pediatric hematology
      oncology patients. The clinical spectrum and the routes of transmission of
      infectious diseases in children have to be considered and preventive strategies
      should be adjusted to host dependent risk factors, in particular to the degree
      and duration of severe immunosuppression (i.e. neutropenia). This article
      overviews practical guidelines to prevent exposure and to reduce external sources
      of infection in immunocompromised children. Scientific evidence from controlled
      randomized studies is lacking or incomplete for many of these measures. A
      systematic and pragmatic approach to the critical control points of patient care
      in pediatric hematology/oncology is prudent to solve this problem in clinical
      practice. The corresponding recommendations are categorized in IV different
      levels of evidence.

PMID- 11577362
TI  - [Antimicrobial prophylaxis of bacterial infections in pediatric oncology
      patients].
AB  - Bacterial infections are still a major challenge in the treatment of pediatric
      cancer patients. Considering the evidence in the literature and published
      consensus opinions of experts the following strategies of antibacterial
      chemoprophylaxis (ABCP) in pediatric cancer patients can be recommended (or not
      recommended): Accompanying the implantation of a ventriculoperitoneal shunt (or a
      Rickham-reservoir) ABCP is recommended, until prospective controlled studies
      including pediatric cancer patients have investigated this issue. In bone marrow
      or stem cell transplant recipients, the prophylactic administration of penicillin
      should be considered, if severe oral mucositis is a common adverse event in
      cancer departments with high rates of penicillin-susceptible strains of
      Streptococcus viridans. Prospective surveillance of resistant bacterial pathogens
      should be an indispensable tool of quality control in pediatric oncology
      departments. The risk of infection with antimicrobial-resistant isolates should
      be balanced against the real benefit of antimicrobial prophylaxis in every
      instance. ABCP should neither be given during implantation nor during prolonged
      usage to prevent bacterial infection of a central venous access device (unproven
      efficacy and potential hazards of Vancomycin-resistant gram-positive infections).
      The oral administration of non-absorbable ABCP or Trimetoprim-Sufomethoxazole is
      not recommended for the prevention of bacterial infections (unproven efficacy)
      and no recommendation can be given for the oral ABCP with chinolones (lacking
      data, risk of antimicrobial resistance).

PMID- 11577363
TI  - [Guidelines for Prevention of Pneumocystis carinii Pneumonitis in Children and
      Adolescents with Cancer].
AB  - Pneumocystis carinii pneumonitis (PCP) is one of the most important opportunistic
      infections in children and adolescents with cancer. Its high frequency and a
      considerable mortality have led to primary chemoprophylaxis in patients with
      hematological malignancies and following allogeneic hematopoietic stem cell
      transplantation. Although less well characterized, patients with autologous stem
      cell transplantation and patients with dose-intensive chemotherapy for pediatric
      solid tumors may have a similarly high risk for PCP based on their profound T
      cell depletion. For more than two decades, effective chemoprophylaxis for PCP has
      been available. Trimethoprim and sulfamethoxazole (TMP/SMX) is the prophylactic
      modality of first choice. The combination has been shown to be almost 100 %
      efficacious in pediatric cancer patients at highest risk, and it is usually well
      tolerated in this setting. Secondary alternatives to TMP/SMX include oral
      dapsone, oral atovaquone, and aerosolized pentamidine-isethionate. These
      modalities are less effective than TMP/SMX, and have been evaluated predominantly
      in HIV-infected patients. This article reviews epidemiology and current
      approaches to chemoprophylaxis for PCP in children and adolescents with cancer
      and/or hematopoietic stem cell transplantation, and provides evidence-based
      guidelines for indications and modalities of PCP prophylaxis in this population.

PMID- 11577364
TI  - [Prevention of fungal infections in children and adolescents with cancer].
AB  - Opportunistic mycoses have emerged as important causes for morbidity and
      mortality in pediatric cancer patients, particularly in those with intensively
      treated hematological malignancies, allogeneic hematopoetic stem cell
      transplantation, and aplastic anemia. The incidence of invasive fungal infections
      in these settings may range from 10 to 25 % despite empirical antifungal therapy
      with an overall case fatality rate of up to 50 and 75 % depending on the
      organism. Preventive interventions are thus warranted, including but not limited
      to chemoprophylaxis with antifungal agents. Effective chemoprophylaxis of
      invasive Candida infections with a long-term benefit for overall survival has
      been demonstrated in patients with allogeneic bone marrow transplantation.
      However, its benefit in other high-risk populations is less well established, and
      a clearly effective approach to chemoprophylaxis for invasive Aspergillus
      infections has not been documented in appropriately designed clinical trials.
      This article reviews epidemiology and current approaches to chemoprophylaxis of
      opportunistic invasive fungal infections in children and adolescents with cancer
      and/or stem cell transplantation, and provides evidence-based guidelines for
      indications and modalities of antifungal prophylaxis and antifungal infection
      control measures in this population.

PMID- 11577365
TI  - [Antiviral prophylaxis].
AB  - Antiviral prophylaxis in pediatric oncology and pediatric bone marrow
      transplantation (BMT)/stem cell transplantation (SCT) focuses herpes viruses:
      herpes simplex virus (HSV), varicella zoster virus (VZV) and cytomegalovirus
      (CMV) since these viruses cause significant morbidity and mortality due to
      primary infection or to reactivation in long term latency. The majority of
      studies on antiviral prophylaxis, especially those on CMV-prophylaxis, have been
      conducted in adult patients. Recommendations for antiviral prophylaxis have been
      published recently by the German "Deutsche Gesellschaft fur padiatrische
      Infektiologie" and by the following American institutions and societies "Centers
      for Disease Control and Prevention", "Infectious Diseases Society of America",
      "American Society of Blood and Marrow Transplantation" who published the
      "Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell
      Transplant Recipients". Concerning HSV- and VZV-prophylaxis there are almost no
      differences between recommendations of the german society and the american
      institutions, however recommendations for preventing CMV-disease and CMV
      recurrence do differ considerably. Controversial aspects of antiviral
      prophylaxis, e.g. VZV vaccination or CMV prevention, should be studied in
      oncology and infectious diseases working groups to define consensus in the near
      future.

PMID- 11577366
TI  - [Vaccination].
AB  - Vaccination has been an important part of antiinfectious prophylaxis in pediatric
      oncology comprising immunizations with special indication like varicella vaccine
      and follow-up of routine immunizations after chemotherapy and bone marrow
      transplantation (BMT). Studies from the last decade demonstrate a loss of long
      term immunity to immunization preventable disease in most patients with
      chemotherapy and BMT who had received appropriate immunization before. So far
      routine vaccination programs following intensive chemotherapy have not been
      studied prospectively. Immunization programs following BMT have shown that
      immunizations with tetanus toxoid, diphtheria toxoid, inactivated poliovirus
      vaccine and influenza vaccine - given at least 12 months after transplantation -
      are safe and effective. Vaccination with live attenuated trivalent vaccine
      against measles, mumps and rubella in patients without chronic "graft versus host
      disease" (GVHD) and without ongoing immunosuppressive therapy, performed 24
      months after transplantation, proved to be safe too. Recommendations have been
      published by 5 different official groups: (1.) "Standige Impfkommission" (STIKO)
      and (2.) "Deutsche Gesellschaft fur padiatrische Infektiologie" (DGPI) recommend
      varicella vaccine fur children with leukemia in remission for at least 12 months,
      for children with solid tumors and for patients getting an organ transplantation.
      Both societies do not comment on the schedule of booster vaccinations (with live
      attenuated vaccines) after the end of chemotherapy and after BMT. (3.)
      "Qualitatssicherungsgruppe" der "Gesellschaft fur padiatrische Onkologie und
      Hamatologie" (QS-GPOH) recommends immunization with nonliving vaccines when the
      patient is off therapy for at least 3 months and immunization with live
      attenuated vaccines when he is off therapy for at least 6 months. This group does
      not comment on varicella vaccine which has been controversial among pediatric
      oncologists. (4.) The " Infectious disease working party of the European group
      for Blood and Marrow Transplantation" (EBMT) recommends immunization with
      nonliving vaccines when the patient is off transplantation for at least 12
      months, without GVHD and without immunosuppressive therapy. (5.) The "Guidelines
      for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant
      (HSCT) Recipients" published by the following american institutions and
      societies: "Centers for Disease Control and Prevention", "Infectious Diseases
      Society of America" and "American Society of Blood and Marrow Transplantation"
      recommend that patients should be routinely revaccinated after transplantation if
      they are off immunosuppressive therapy and do not suffer from GVHD: beginning of
      vaccinations with nonliving vaccines in the second year after HSCT, beginning of
      vaccinations with live attenuated vaccines in the third year after HSCT. Life
      long seasonal influenza vaccination is recommended for all HSCT candidates and
      recipients, beginning during the influenza season before HSCT and resuming > 6
      months after HSCT. IT would be appreciated if working groups of these societies
      could find consensus recommendations on open and controversial questions in the
      near future.

PMID- 11577367
TI  - [Antiinfectious prophylaxis in asplenia].
AB  - Asplenia in childhood may be congenital (e.g. Ivemark-syndrome) or acquired
      (functional hyposplenism in sickle cell disease; after splenectomy or bone marrow
      transplantation). Hereditary spherocytosis is the most common indication for
      splenectomy in childhood. Virtually every patient without spleen has a
      significantly increased risk of severe postsplenectomy infection (mostly caused
      by Streptococcus pneumoniae). Therefore, vaccinations against pneumococci,
      haemophilus influenzae and, under certain circumstances, meningococci are
      recommended. In addition a continuous prophylaxis with antibiotics should be
      performed for at least three years (or even longer depending on the disease)
      after splenectomy followed by lifelong interventional application of broad
      spectrum antibiotics in case of any unclear infection or high fever. This
      prophylaxis must be started as early as four months of age in sickle cell
      disease. In future the use of penicillin may be hampered by the growing
      resistance of pneumococci. Due to this fact the indication for splenectomy in
      childhood should be restricted to patients with hematologic disease
      (spherocytosis and other hemolytic anemias, chronic ITP etc.) and moderate to
      severe symptoms. It is unclear whether partial splenectomy for spherocytosis (and
      other hemolytic anemias) is an alternative regarding both longlasting reduction
      of hemolysis and prevention of severe infection. After trauma every effort should
      be undertaken to preserve a splenic remnant.

PMID- 11577368
TI  - [Hematopoietic growth factors in the prevention of infections complications in
      children with hematologic-oncologic diseases].
AB  - The hematopoietic colony-stimulating factors have been introduced into clinical
      practice as additional supportive measures that can reduce, but not eliminate
      infectious complications associated with therapy-induced neutropenia. Over the
      past decade, we have begun to appreciate the subtler aspects of the proper use of
      G-CSF and GM-CSF, identifying appropriate indications and contraindications. In
      the course of evaluating the multitude of studies, a set of formal
      recommendations have been propagated for the judicious use of these expensive
      growth factors. To prevent serious infection, the use of G- or GM-CSF is
      recommended in a subset of pediatric cancer patients shortly after receiving
      chemotherapy or a marrow transplant. Children with intensive chemotherapy (e.g.,
      children with high risk ALL, NHL or metastatic neuroblastoma) seem to benefit
      from hematopoietic growth factors whereas it is not clear that this applies to
      children undergoing therapy for solid tumors such as rhabdomyosarcoma or Ewing's
      sarcoma. An exciting development is the use of G-CSF and GM-CSF to mobilize
      peripheral-blood progenitor cells. Future studies in pediatric cancer patients
      are clearly warranted to address several issues. Prospective clinical trials are
      still needed to define specific treatment groups who can benefit from growth
      factor support. In this regard, efforts must be directed at better defining the
      endpoints and in particular, assigning value to reduction in treatment of
      possible infectious complications, such as days in hospital, antibiotic usage and
      costs. In addition, randomized studies are required to evaluate the proper dosage
      and duration of therapy, which most likely will vary between groups, depending
      upon underlying malignancy and therapy given. In addition, combinations of
      different growth factors have to be tested, particularly if ex vivo expansion and
      the storage of hematopoietic stem cells are to be utilized in a wider spectrum of
      patients.

PMID- 11577369
TI  - [Intravenous immunoglobulins in the prevention of infection in children with
      hematologic-oncologic diseases].
AB  - Treatment with intensive myelosuppressive therapy results in decreased levels of
      immunoglobulins. Whereas pediatric cancer patients undergoing chemotherapy do not
      benefit from the routine administration of intravenous immunoglobulins,
      prophylactic intravenous immunoglobulins given after bone marrow transplantation
      or after peripheral stem cell transplantation reduce infectious complications.
      Still, prospective clinical trials are needed to define specific treatment groups
      who can benefit from immunoglobulin support. In addition, randomized studies are
      required to evaluate the proper dosage and duration of therapy. Passive
      immunization of children potentially incubated with varicella or measles is
      generally recommended.

PMID- 11577370
TI  - [Surveillance for nosocomial infections in pediatric hematology/oncology
      patients].
AB  - Immunocompromised patients in pediatric hematology-oncology are faced with an
      increased risk of nosocomial infections (NI). The incidence of NI and the
      contribution of certain risk factors have not sufficiently been investigated in
      this population. It is therefore unknown how many NI are preventable through
      infection control measures. The surveillance of NI in pediatric hematology
      oncology departments should focus on device-associated infections (central venous
      catheter infection, urinary tract infection), on nosocomial pneumonia (in
      particular due to Aspergillus) and on infectious complications caused by
      Respiratory Syncytial-Virus and Rotavirus. The surveillance protocol should be
      based on a modified version of the Centers for Disease Control and Prevention
      methods (established definitions of NI can not be completely applied to pediatric
      oncology patients). Prospective surveillance for NI on pediatric
      hematology/oncology units is an indispensable tool for internal quality control.
      The careful evaluation of specific NI-rates permits the identification of
      critical control points, that may be targeted by infection control programs.

PMID- 11577371
TI  - Haploinsufficiency for one COL3A1 allele of type III procollagen results in a
      phenotype similar to the vascular form of Ehlers-Danlos syndrome, Ehlers-Danlos
      syndrome type IV.
AB  - Mutations in the COL3A1 gene that encodes the chains of type III procollagen
      result in the vascular form of Ehlers-Danlos syndrome (EDS), EDS type IV, if they
      alter the sequence in the triple-helical domain. Although other fibrillar
      collagen-gene mutations that lead to allele instability or failure to incorporate
      proalpha-chains into trimers-and that thus reduce the amount of mature molecules
      produced-result in clinically apparent phenotypes, no such mutations have been
      identified in COL3A1. Furthermore, mice heterozygous for Col3a1 "null" alleles
      have no identified phenotype. We have now found three frameshift mutations
      (1832delAA, 413delC, and 555delT) that lead to premature termination codons
      (PTCs) in exons 27, 6, and 9, respectively, and to allele-product instability.
      The mRNA from each mutant allele was transcribed efficiently but rapidly
      degraded, presumably by the mechanisms of nonsense-mediated decay. In a fourth
      patient, we identified a point mutation, in the final exon, that resulted in a
      PTC (4294C-->T [Arg1432Ter]). In this last instance, the mRNA was stable but led
      to synthesis of a truncated protein that was not incorporated into mature type
      III procollagen molecules. In all probands, the presenting feature was vascular
      aneurysm or rupture. Thus, in contrast to mutations in genes that encode the
      dominant protein of a tissue (e.g., COL1A1 and COL2A1), in which "null" mutations
      result in phenotypes milder than those caused by mutations that alter protein
      sequence, the phenotypes produced by these mutations in COL3A1 overlap with those
      of the vascular form of EDS. This suggests that the major effect of many of these
      dominant mutations in the "minor" collagen genes may be expressed through protein
      deficiency rather than through incorporation of structurally altered molecules
      into fibrils.

PMID- 11577372
TI  - Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior
      polar cataract in humans.
AB  - Congenital cataracts are an important cause of bilateral visual impairment in
      infants. In a four-generation family of English descent, we mapped dominant
      congenital posterior polar cataract to chromosome 11q22-q22.3. The maximum LOD
      score, 3.92 at recombination fraction 0, was obtained for marker D11S898, near
      the gene that encodes crystallin alpha-B protein (CRYAB). By sequencing the
      coding regions of CRYAB, we found in exon 3 a deletion mutation, 450delA, that is
      associated with cataract in this family. The mutation resulted in a frameshift in
      codon 150 and produced an aberrant protein consisting of 184 residues. This is
      the first report of a mutation, in this gene, resulting in isolated congenital
      cataract.

PMID- 11577374
TI  - A randomized, double-blind, double-dummy, multicenter trial of voriconazole and
      fluconazole in the treatment of esophageal candidiasis in immunocompromised
      patients.
AB  - The efficacy, safety, and tolerability of voriconazole and fluconazole were
      compared in 391 immunocompromised patients with mycology- and biopsy-proven
      esophageal candidiasis. Primary efficacy analysis (256 patients) of esophageal
      treatment as assessed by esophagoscopy revealed success rates of 98.3% with
      voriconazole and 95.1% with fluconazole. The 95% confidence interval for the
      difference in success rates ranged from -1.0% to 7.5%. The overall safety and
      tolerability of both antifungals were acceptable. Fewer patients discontinued
      voriconazole treatment because of insufficient clinical response (4 patients
      [2.0%] vs. 5 patients [2.6%]). More patients discontinued voriconazole than
      fluconazole treatment because of laboratory test abnormalities (7 patients [3.5%]
      vs. 2 patients [1.0%]) or treatment-related adverse events (5 patients [2.5%] vs.
      1 patient [0.5%]). The most frequent adverse events (23%) with voriconazole were
      mild, transient visual disturbances. Voriconazole (200 mg, b.i.d.) was shown to
      be at least as effective as fluconazole in the treatment of biopsy-proven
      esophageal candidiasis in immunocompromised patients.

PMID- 11577373
TI  - At the speed of sound: gene discovery in the auditory system.
AB  - As auditory genes and deafness-associated mutations are discovered at a rapid
      rate, exciting opportunities have arisen to uncover the molecular mechanisms
      underlying hearing and hearing impairment. Single genes have been identified to
      be pathogenic for dominant or recessive forms of nonsyndromic hearing loss,
      syndromic hearing loss, and, in some cases, even multiple forms of hearing loss.
      Modifier loci and genes have been found, and investigations into their role in
      the hearing process will yield valuable insight into the fundamental processes of
      the auditory system.

PMID- 11577375
TI  - Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient
      receiving antiviral maintenance: clinical and molecular evidence of drug
      resistance.
AB  - We describe a case of CMV ventriculoencephalitis in a severely immunocompromised
      bone marrow transplant recipient who was receiving combination therapy with
      ganciclovir and foscarnet for treatment of viremia and retinitis. Analysis of
      sequential viral isolates recovered from the patient's cerebrospinal fluid
      suggested that disease developed because of the presence of viral resistance and,
      possibly, low tissue penetration of antiviral agents.

PMID- 11577376
TI  - Cerebrospinal fluid penetration of levofloxacin in patients with spontaneous
      acute bacterial meningitis.
AB  - We have assessed levofloxacin penetration in cerebrospinal fluid (CSF) and the
      liquor-to-plasma ratio (C(L)/C(P)) at 2 hours after dosing in 5 patients with
      spontaneous acute bacterial meningitis. CSF levofloxacin concentration at 2 hours
      after dosing was 1.99+/-0.67 microg/mL, and the C(L)/C(P) at 2 hours after dosing
      was 0.34+/-0.09.

PMID- 11577377
TI  - Complement C4 deficiency and HLA homozygosity in patients with frequent intraoral
      herpes simplex virus type 1 infections.
AB  - Three consecutive patients with no apparent immunodeficiency who had frequent
      intraoral herpes simplex type 1 recurrences, a rare complication of herpes
      simplex virus infection, were found to have a total deficiency of either the A or
      B isotype of the complement component C4 and to be homozygous for the studied HLA
      antigens. A combination of HLA homozygosity, which may lead to impaired T cell
      recognition of viral peptides, and deficiency in the classical complement
      pathway, which can compromise virus neutralization, may predispose to severe and
      frequent herpes simplex virus infections.

PMID- 11577378
TI  - Device-associated infections: a macroproblem that starts with microadherence.
AB  - Medical devices are responsible for a large portion of nosocomial infections,
      particularly in critically ill patients. Device-associated infections can cause
      major medical and economic sequelae. Bacterial colonization of the indwelling
      device can be a prelude to both infection and malfunction of the device. The
      pathogenesis of device-associated infection centers around the multifaceted
      interaction among the bacteria, the device, and the host. Bacterial factors are
      probably the most important in pathogenesis of infection, whereas device factors
      are the most amenable to modification with the objective of preventing infection.
      Some, but not all, of the studied bacterial receptors satisfy the proposed
      "adherence/infection" version of Koch's postulates. Traditional surface-modifying
      preventive approaches have largely focused on antimicrobial coating of devices
      and resulted in variable clinical success in preventing device-associated
      infections. The potential protective role of newer innovative approaches, such as
      biofilm modification and bacterial interference, ought to be further
      investigated.

PMID- 11577379
TI  - Measuring the economic costs of antimicrobial resistance in hospital settings:
      summary of the Centers for Disease Control and Prevention-Emory Workshop.
AB  - Health systems administrators and clinicians need refined calculations of the
      attributable cost of infections due to drug-resistant microorganisms to develop
      and assess cost-effective prevention strategies that deal with these infections.
      To date, however, efforts to provide this information have yielded widely
      variable and often conflicting estimates. This lack of reproducibility is largely
      attributable to problems in study design and in the methods used to identify and
      measure costs. Addressing these methodological issues was the focus of a workshop
      that included participants from a broad range of backgrounds, including
      economics, epidemiology, health care management, health care outcomes research,
      and clinical care. This workshop summary presents the advantages and
      disadvantages of various research designs as well as particular methodological
      issues related to the measurement of the economic cost of resistance in health
      care settings. Suggestions are made for needed common definitions and approaches,
      study areas for future research are considered, and priority investigations are
      identified.

PMID- 11577380
TI  - A novel approach for solving constrained nonlinear optimization problems using
      neurofuzzy systems.
AB  - A neural network model for solving constrained nonlinear optimization problems
      with bounded variables is presented in this paper. More specifically, a modified
      Hopfield network is developed and its internal parameters are computed using the
      valid-subspace technique. These parameters guarantee the convergence of the
      network to the equilibrium points. The network is shown to be completely stable
      and globally convergent to the solutions of constrained nonlinear optimization
      problems. A fuzzy logic controller is incorporated in the network to minimize
      convergence time. Simulation results are presented to validate the proposed
      approach.

PMID- 11577381
TI  - Evolutionary optimization of RBF networks.
AB  - One of the main obstacles to the widespread use of artificial neural networks is
      the difficulty of adequately defining values for their free parameters. This
      article discusses how Radial Basis Function (RBF) networks can have their
      parameters defined by genetic algorithms. For such, it presents an overall view
      of the problems involved and the different approaches used to genetically
      optimize RBF networks. A new strategy to optimize RBF networks using genetic
      algorithms is proposed, which includes new representation, crossover operator and
      the use of a multiobjective optimization criterion. Experiments using a benchmark
      problem are performed and the results achieved using this model are compared to
      those achieved by other approaches.

PMID- 11577382
TI  - Public gives hospitals scores in customer satisfaction.

PMID- 11577383
TI  - Improving data collection in four easy steps.

PMID- 11577384
TI  - Medical privacy--what you need to know.

PMID- 11577385
TI  - The 6.8 quake--Seattle style.

PMID- 11577386
TI  - Jumping in ... are you ready to take the ASP plunge?

PMID- 11577387
TI  - The automation of coordination of benefits.

PMID- 11577388
TI  - [Use of liquid chromatography/mass spectrometry in food analysis].

PMID- 11577389
TI  - [Comparison of photometric, electrochemical and post-column fluorescence
      detection for the determination of flavonoids by HPLC].
AB  - For the analysis of flavonoids by HPLC, we compared three different detection
      methods, namely UV, electrochemical detection and post-column chelation with
      aluminum followed by fluorescence detection. Ten flavonoids were used: apigenin,
      myricetin, luteorin, taxifolin, quercetin-3-O-sulfate, kaempferol, isorhamnetin,
      isoquercitrin, quercetin and rutin. Nine flavonoids except apigenin were
      efficiently detected by the electrochemical method with a detection limit of
      0.025-0.05 pmol. Flavonols having free 3-hydroxyl and 4-keto oxygen formed a
      fluorescent complex by post-column chelation and were detected by the
      fluorescence method. The detection limit of the fluorescence method was 0.05-0.5
      pmol. Nine flavonoids except taxifolin were detected by the UV method (absorbance
      at 370 nm), but the detection level was poor (5-10 pmol). Flavonols added to
      human plasma were recovered by solid phase extraction, and were analyzed using
      the three detection methods. Most of the flavonols were efficiently detected by
      the electrochemical and fluorescence methods, and the detection limits were
      similar to those of standard samples.

PMID- 11577390
TI  - [Residual chemicals in natural rubber products for food contact use].
AB  - The residues of additives and other chemicals were investigated by GC/MS in
      natural rubber products for food contact, which included nipples, packing, gloves
      and a net for ham. The packings and gloves contained 980-6,570 micrograms/g of
      vulcanization accelerators, such as zinc dimethyldithiocarbamate, zinc
      diethyldithiocarbamate (EZ), zinc di-n-buthyldithiocarbamate (BZ) and 2
      mercaptobenzothiazole. Some samples contained BHT, Irganox 1076 and Yoshinox
      2246R as antioxidants; dibutyl phthalate and di(2-ethylhexyl) phthalate as
      plasticizers; and palmitic acid, stearic acid, palmitamide, stearamide and
      hydrocarbons as lubricants. Two unknown peaks were identified as stigmasterol and
      beta-sitosterol, and others were estimated to be fucosterol, oryzanol and alpha
      sitosterol. These sterols are widely distributed in plants, so their origin was
      presumed to be the rubber plants. The sterols were detected at a level of 340
      2,940 micrograms/g in all natural rubber samples. A migration test was carried
      out for some samples. No chemicals were released into water, 4% acetic acid or
      20% ethanol at 60 degrees C for 30 min, though BHT, Yoshinox 2246R, EZ, BZ and
      sterols were released into n-heptane at 25 degrees C for 60 min.

PMID- 11577391
TI  - [Establishment of animal model for elucidating the mechanism of intoxication by
      the poisonous mushroom Clitocybe acromelalga].
AB  - Dietary intake of a poisonous mushroom, Clitocybe acromelalga, causes
      acromelalgia. The symptom continues for over a month. Some papers reported that
      treatment with nicotinic acid is effective. We have established an animal model
      to elucidate the mechanism of toxicity of the poisonous mushroom Clitocybe
      acromelalga. Diet containing Clitocybe acromelalga was fed to niacin-deficient
      rats for 24 hours (designated as day 0). The food intake decreased to about one
      half compared with that of day before, and body weight loss was noted. Although
      the diet was returned to the control diet on day 1, the food intake did not
      recover until day 7, and body weight gain was not seen until day 6. A severe
      symptom resembling acromelalgia in humans started to appear on day 3. This is the
      first report of an animal model for the intoxication of Clitocybe acromelalga in
      humans. Since no similar symptom resembling human intoxication was seen in a
      previous rodent study, the niacin-free/tryptophan-limited diet used in the
      present study may have contributed to the result.

PMID- 11577392
TI  - [Effect of feeding with a poisonous mushroom Clitocybe acromelalga on the
      metabolism of tryptophan-niacin in rats].
AB  - The poisonous mushroom Clitocybe acromelalga contains clitidine, which resembles
      nicotinic acid mononucleotide, and 4-amino-pyridine-2,3-dicarboxylic acid, which
      resembles quinolinic acid. Both are important intermediates in the tryptophan
      niacin pathway. Therefore, we investigated the effect of feeding a niacin-free
      and tryptophan-limited diet containing the toadstool Clitocybe acromelalga on the
      metabolism of tryptophan to niacin in rats. The toadstool diet was fed to the
      rats for only one day (this day was designated day 0). Urinary excretion of
      intermediates in the tryptophan-niacin pathway, such as anthranilic acid,
      kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, quinolinic acid,
      nicotinamide, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1
      methyl-4-pyridone-3-carboxamide, was higher in the toadstool group than in the
      control on day 0-day 1 and day 1-day 2. The blood levels of tryptophan and NAD on
      day 1 were also higher in the toadstool group. Accordingly, intake of Clitocybe
      acromelalga appeared to increase the conversion of tryptophan to niacin.

PMID- 11577393
TI  - [A detection method for recombinant DNA from genetically modified maize CBH351].
AB  - A method using polymerase chain reaction (PCR) was designed for the detection of
      genetically modified maize CBH351, which has not authorized as safe for use in
      foods and feeds in Japan yet. We analyzed a recombinant DNA (r-DNA) sequence
      introduced into CBH351 maize and designed specific primer pairs to amplify a
      segment including part of the r-DNA. The PCR products obtained by using the
      designed primer pairs are specific for CBH351 and should prevent false positive
      results caused by other maizes and other main cereal crops. The r-DNA introduced
      into CBH351 could be detected from maize samples containing 0.05-0.1% CBH351
      maize. This sensitivity is theoretically equivalent to a level of several genome
      copies and so this technique is a very efficient means to detect CBH351 maize.

PMID- 11577394
TI  - [Origin of sennosides in health teas including Malva leaves].
AB  - The aim of this study is to clarify whether sennosides are contained in the leaf
      of Malva verticillata L., and then to clarify the source of sennosides in health
      teas including malva leaves. The identification and determination of sennosides
      were performed with thin layer chromatography and high performance liquid
      chromatography. The leaf of Malva verticillata L. did not contain sennosides A or
      B and could be easily distinguished from senna leaf. Our previous report showed
      that sennosides are contained in weight-reducing herbal teas including malva
      leaves, and that senna leaf is a herbal component in some teas. Furthermore, in
      10 samples of health tea including malva leaves that were bought last year, the
      smallest amount of sennosides was 6.1 mg/bag, and all health teas including malva
      leaves contained the leaf and midrib of senna. We suggest that sennosides A and B
      are not contained in the leaf of Malva verticillata L., and that the sennosides
      in health teas including malva leaves are not derived from malva leaf but from
      senna leaf.

PMID- 11577395
TI  - [Detection of O,O,S-trimethyl phosphorodithioate, an impurity in phenthoate
      (PAP), in komatsuna].
AB  - An unknown peak (peak A) was detected in a mass chromatogram of komatsuna extract
      containing a high concentration of phenthoate (PAP), and it was considered to be
      O,O,S-trimethyl phosphorodithioate (OOS). Although it is generally known that OOS
      exists as an impurity in technical malathion and PAP, it has not been reported
      that OOS is present in crops. Since an OOS standard is not commercially
      available, OOS was separated and purified from commercial emulsifiable malathion.
      Peak A was confirmed to be OOS by GC/MS using the purified OOS. The concentration
      of OOS was estimated to be 0.02 microgram/g. It is supposed that OOS was detected
      in crops because they contained a high concentration of PAP residue.

PMID- 11577396
TI  - [Method-performance studies of notified analytical method for fenbutatin oxide
      and cyhexatin].
AB  - Method-performance studies were conducted for the notified revised analytical
      method of fenbutatin oxide (FBTO) and cyhexatin (CHT). FBTO and CHT spiked into
      rice, soybeans, spinach, orange, tea powder and tea extract at the level of 0.5
      microgram/g for FBTO and 0.1 microgram/g for CHT were analyzed in replicate in 6
      laboratories. Means recoveries of FBTO were 85.2-96.5% and those of CHT were 83.5
      89.2% except from soybeans (46.5%). Repeatability relative standard deviation
      values of FBTO and CHT in each crop were in the ranges of 2.3-9.4% and 3.2-6.3%,
      respectively. Reproducibility relative standard deviations were 3.9-12.6% for
      FBTO and 8.3-12.9% for CHT. Detection limits were 0.015-0.05 microgram/g for FBTO
      and 0.005-0.02 microgram/g for CHT.

PMID- 11577397
TI  - [Food labelling system by the amendment of Japan Agricultural Standard Law].

PMID- 11577398
TI  - [Quality of raw milk produced in Hokkaido and quality control activity on farm].

PMID- 11577399
TI  - [Method of tumor-promoters using cultured cells].

PMID- 11577400
TI  - [Japanese children with rheumatic diseases are not satisfied].

PMID- 11577401
TI  - [Therapeutic plasmapheresis for the prevention of congenital complete heart block
      associated with anti-SS-A/Ro antibody and anti-SS-B/La antibody].
AB  - OBJECTIVES: Neonatal lupus erythematosus is characterized by transient lupus
      abnormalities, various systemic and hematological abnormalities, and congenital
      complete heart block (CCHB). It is well known that anti-SS-A/Ro antibody (52
      kD/60 kD) and anti-SS-B/La antibody are associated with CCHB. This study was
      conducted to evaluate the effects of the removal of anti-SS-A/Ro antibody (52
      kD/60 kD) and anti-SS-B/La antibody from plasma in pregnant women whose fetuses
      are at a high risk of developing CCHB. MATERIALS & METHODS: Fifteen pregnant
      patients positive for anti-SS-A/Ro antibody and anti-SS-B/Laantibody were
      subjected weekly to double filtration plasmapheresis to remove both antibodies.
      Antibody titers were measured by double immunodiffusion (DID) and ELISA. RESULTS:
      As a result, all women gave birth to live babies, but CCHB was recognized in one
      baby. No transient lupus abnormalities were recognized in any of the babies.
      Fourteen patients showed decreased antibody titers by ELISA during
      plasmapheresis. However, the patient who was delivered of a baby with CCHB showed
      an increase of antibody titers by ELISA while the DID method showed a decrease of
      antibody titers. CONCLUSION: Our study suggested that plasmapheresis prevents
      CCHB associated with anti-SS-A/Ro and anti-SS-B/La antibody. Also, it is
      important to monitor the antibody titer regularly during the course of pregnancy,
      because it may increase due to worsening of the mother's primary disease.

PMID- 11577402
TI  - [Clinical study on mortality of rheumatoid arthritis compared with malignant
      rheumatoid arthritis].
AB  - OBJECTIVE: To determine how the mortality of patients with rheumatoid arthritis
      (RA) behave in comparison with that of patients with malignant rheumatoid
      arthritis (MRA). METHODS: The mortality of RA patients selected at randam
      identified in 1991-2000 (n = 104) was compared with that of 18 MRA patients.
      Hazard ratios of death were calculated with a multivariate survival analysis. A
      clinical study of patients with both RA and MRA was performed in mortality.
      RESULTS: Excess mortality was seen in MRA patients in Kaplan-Meier survival
      curves (p = 0.02 by log-rank test). MRA patients were treated more often with
      cytostatic and immunosuppressive drugs. Infection was the main cause of death in
      both RA and MRA patients. Vasculitis was not reported as the cause of death in
      MRA patients. Secondary amyloidosis played an important role in RA death rather
      than MRA. CONCLUSION: There remained an excess mortality in MRA patients compared
      with RA, and infection was attributable to the key cause of death in both RA and
      MRA suggesting therapeutic side effects.

PMID- 11577403
TI  - [Minocycline for the treatment of bronchiolitis obliterans associated with
      rheumatoid arthritis].
AB  - We discribe a rare case of rheumatoid arthritis (RA) complicated with
      bronchiolitis obliterans that was successfully treated with minocycline. Sixty
      four-year old woman with a four-years history of RA was admitted to the hospital
      because of dyspnea on exertion and polyarthritis. Pulmonary function test
      revealed marked decrease in V25 (0.10 l/s: 6.9%) and MMFR (12.6%). High
      resolution CT of the lung showed scattered centri-lobular micronodules in both
      lung fields, mucoid impaction, and hyperinflation. These findings indicated the
      presence of bronchiolitis obliterans. After 3 months of the treatment with
      minocycline, the patient showed a significant improvement of both arthritis and
      pulmonary function. Chest CT findings also improved after 1 year. The present
      case suggests that minocycline is effective for the treatment of bronchiolitis
      obliterans seen in patients with RA.

PMID- 11577404
TI  - [Destructed knee in patient with systemic lupus erythematosus treated with total
      knee arthroplasty: a case report].
AB  - We reported a case of a 61-year-old female with arthritis of right knee
      associated with systemic lupus erythematosus (SLE). She suffered from SLE at age
      31 and felt pain around her right knee at age 60. It gradually increased despite
      intraarticular injections of steroid and arthroscopic synovectomy. On admission,
      the range of motion of her right knee was 20 to 135 degrees and remarkable gait
      disturbance were noted due to the pain. Radiographs of the right knee showed
      joint space narrowing and bone erosion. YMCK total knee arthroplasty was
      performed. Operation findings showed smooth and thick synovium and cartilage
      defect. Histological examination revealed fibrin on surface, proliferad
      connective tissue and newly development of vasculature. Synovium eroded both
      cartilage and bone. In SLE, soft tissue contructure was reported to be a main
      cause of joint dislocation, but there were only a few report of progressive joint
      destruction due to SLE. In this case, the main cause of joint destruction may be
      invasion synovium into cartilage and bone.

PMID- 11577405
TI  - [3 cases of polymyalgia rheumatica (PMR), in which serum amyloid A was a useful
      index of the disease activity].
AB  - We encountered 3 cases of polymyalgia rheumatica (PMR), in which serum amyloid A
      (SAA) levels were correlated with clinical pictures after normalization of ESR
      and CRP levels. Therefore, it is suggested that SAA may be a useful index for
      evaluating the severity of intractable PMR. Case 1: The patient was a 75-year-old
      man. Although ESR and CRP levels were normalized after the administration of PSL
      (20 mg/day), myalgia persisted. When the dose of PSL was reduced, PMR recurred,
      which was relieved by administering 15 mg/day of PSL. However, myalgia recurred
      again when the dose of PSL was reduced thereafter. The elevated SAA level (33.0
      micrograms/ml) was normalized by continuous administration of PSL without
      reducing the dose, resulting in the relief of myalgia. Case 2: The patient was a
      65-year-old woman. The administration of PSL was initiated at a dose of 15
      mg/day. Although myalgia was relieved, the symptom and elevated SAA levels
      persisted for approximately 3 months. Thereafter, PMR recurred, and SAA levels
      were markedly increased to 78.2 micrograms/ml. However, the symptom of PMR was
      eliminated by continuously administering PSL without reducing the dose. Although
      the dose of PSL was then reduced after the decrease in SAA levels, PMR did not
      recur. Case 3: The patient was an 88-year-old woman. Although the symptom of PMR
      was relieved by administering 15 mg/day of PSL, myalgia persisted. Since SAA
      levels were increased to 106 micrograms/ml, PSL was continuously administered
      without reducing the dose, resulting in the disappearance of the symptom and
      normalization of SAA levels approximately 3 months later. Although the dose of
      PSL was then reduced to 12.5 mg/day, PMR did not recur.

PMID- 11577406
TI  - [Disease genes of rheumatoid arthritis].

PMID- 11577407
TI  - [DNA chip and disease related genes].

PMID- 11577408
TI  - [NO in host defense and microbial pathogenesis].

PMID- 11577409
TI  - [Vacuolating cytotoxin (VacA) and cag pathogenicity island (PAI) of Helicobacter
      pylori].

PMID- 11577410
TI  - [Serratia marcescens as an opportunistic human pathogen].

PMID- 11577411
TI  - [Treatment of multiple sclerosis: current opinion].

PMID- 11577412
TI  - [Central nervous system involvement in decompression illness].

PMID- 11577413
TI  - [Follow-up study of myasthenia gravis: evaluation of thymectomy in 300 patients].
AB  - From June 1975 to March 1999, 300 patients of myasthenia gravis(MG) have
      undergone thymectomy. Among these patients, 69 cases were classified as ocular
      type of MG(including 15 cases with thymoma), and 231 were generalized type of
      MG(including 86 cases with thymoma). The efficacy of the treatment was
      investigated by evaluating current patients' life activity, which is classified
      in 6 groups(Remission, Much Improved, Improved, Unchanged, Worse, and Died).
      Among the 214 cases without thymoma, Remission was 75, Much Improved was 56, and
      Improved was 55, namely 86.9% of these cases showed Improved or better. Among 86
      cases with thymoma, Remission was 14, Much Improved was 21, and Improved was 32,
      namely 77.9% of these cases showed Improved or better. We concluded that post
      operative outcome of these patients regardless of thymoma were generally
      satisfactory, but it was necessary to carry out long term careful follow-up.

PMID- 11577414
TI  - [The number and form of cerebellar fastigial neurons projecting to the thalamic
      suprageniculate nucleus in cats studied using WGA-HRP tracing method].
AB  - This study was designed to investigate the number and form of cerebellar
      fastigial neurons projecting to the suprageniculate nucleus(Sg) by using
      retrograde axonal transport of wheat germ agglutinin-horseradish peroxidase(WGA
      HRP). Six adult cats(weighing 2.5-3.5 kg) were anesthetized with ketamine
      hydrochloride(30 mg/kg, i.m.) and sodium pentobarbital(15 mg/kg, i.p.). In
      experiments using injected WGA-HRP in the Sg, retrogradely labeled neurons by WGA
      HRP were found only in the caudal part of the bilateral fastigial nucleus (Ft)
      with ipsilateral predominance, and the ratio of labeled neurons in the
      contralateral Ft to that in the ipsilateral Ft in all cats was 496:670(1:1.35).
      Five types of Ft-Sg neurons were distinguished morphologicaly. Of the 246 labeled
      neurons that could be characterized, 6.1% were large stellate neurons, 43.5%
      medium stellate neurons, 24.0% bipolar neurons, 20.3% triangular neurons, and
      6.1% granular neurons. Thus, we concluded that a mixed population of Ft neurons
      projects to the Sg. In summary, as shown in the Figure 4 the Ft-Sg connection is
      an important pathway joining two closed circuits, and can be part of the
      extrageniculate visual system. We also speculate that the Ft-Sg connections may
      have a role in sending visual modulating information.

PMID- 11577416
TI  - [A case of urinary retention secondary to aseptic meningitis].
AB  - A case of a 37-year-old man with urinary retention secondary to aseptic
      meningitis is described. He was admitted to our hospital with complaints of
      fever, nausea, headache, and gait disturbance. He had begun treatment 1 week
      previously for high fever, headache and joint pain at an outpatient department.
      On admission, neurological examination revealed neck stiffness, spasticity and
      hyperreflexia of the extremities, hypesthesia of the lower extremities, and
      ataxic gait. A spinal fluid examination revealed aseptic meningitis. Disturbed
      consciousness, diplopia, aphasia, tetraparesis, and urinary retention appeared
      after admission. Computed tomography and magnetic resonance imaging (MRI) of the
      head revealed no abnormal lesions. On the 2nd day of hospitalization, a Foley
      catheter was inserted for urinary retention. The patient was treated with
      conservative therapy, and his symptoms gradually resolved. The Foley catheter was
      removed on hospital day 13, but bladder dysfunction was persisted. MRI of the
      lumbar spine revealed herniated lumbar discs at level L3-4, L4-5, and L5-S1, but
      the nerve roots were not compressed. The patient was managed with clean
      intermittent catheterization for more than two weeks. Cystometry revealed atonic
      bladder. Nineteen cases of urinary retention secondary to aseptic meningitis have
      been reported in the previous literature. We reviewed their clinical presentation
      and treatment.

PMID- 11577415
TI  - [Risk factor for cerebral hemorrhage for the patient with lacunar infarction:
      investigation of 5 cases associated with both of symptomatic hemorrhagic and
      ischemic strokes].
AB  - BACKGROUND AND PURPOSE: Microangiopathy is regarded as an important cause of
      intracerebral hematoma(ICH) and lacunar infarction. Dot-like low intensity spots
      on T2-weighted echo planar image(EPI) have been regarded as hemosiderin deposit
      associated with microangiopathy. However, clinical significance of dot-like
      hemosiderin spot(dotHS) is still debated. Therefore, we analyzed the number of
      dotHS on EPI of symptomatic lacunar infarction associated with ICH. METHODS: To
      investigate how the dotHS or risk factors contributed to hemorrhagic strokes for
      patients with lacunar infarction, the number of dotHS and various risk factors
      were made a comparison between 20 cases with symptomatic lacunar
      infarctions(lacunar group) and 5 cases with both symptomatic lacunar infarction
      and symptomatic ICH(complicated group). In addition to EPI, fluid attenuated
      inversion recovery image, and T1- and T2-weighted MR images were performed for
      differential diagnosis of dot HS. RESULTS: EPI demonstrated that asymptomatic ICH
      was significantly more frequent in complicated group (60%) than in lacunar
      group(10%), and dotHS were significantly more frequent in complicated group(100%)
      than in lacunar group(50%). The number of dotHS of complicated group was 14.6 +/-
      4.3, which was significantly larger than that of lacunar group(4.1 +/- 9.2). No
      significant difference between two groups were founded in other risk factors
      including hypertension, diabetes mellitus, hyperlipidemia, and smoking.
      CONCLUSION: These results suggested that dotHS was one of the risk factors for
      ICH for patients with symptomatic lacunar infarction, and an increasing number of
      dotHS was one of the predictive factors of symptomatic and/or asymptomatic ICH.

PMID- 11577417
TI  - [A case of anaplastic astrocytoma arising 8 years after initial treatment by
      partial resection and irradiation for central neurocytoma].
AB  - A 31-year-old female developed the anaplastic astrocytoma in the right basal
      ganglia and temporal lobe 8 years after partial resection and irradiation of the
      central neurocytoma. Probably the malignant astrocytoma was an irradiation
      induced tumor. Postoperative radiation therapy for the central neurocytoma
      appears to have a good effect on tumor local control. But it should be carefully
      decided whether to use radiation therapy for residual tumor because of the risk
      of delayed complications of irradiation, such as the present case.

PMID- 11577418
TI  - [Pachymeningitis with autonomic dysfunctions: a case report].
AB  - A 67-year-old man temporarily complained of hearing loss and earache in the left
      side. Afterwards, hearing impairment in the right, pharyngalgia, dysphagia, and
      ipsilateral facial weakness occurred, however, otological treatments did not
      completely improve these symptoms except facial weakness. On admission
      neurological examination revealed right cranial nerve palsies(IX, X, XII), and
      severe orthostatic hypotension was noted one month after admission. Cerebrospinal
      fluid revealed pleocytosis(16/mm3), and increased protein level(91 mg/dl), but
      bacterial, and tuberculotic cultures were negative. Cranial and neck magnetic
      resonance imaging with gadolinium administration showed diffuse dural thickening.
      Autonomic dysfunctions were found in cardiovascular and pupillary systems. Plasma
      noradrenaline level was normal in supine position but noradrenaline infusion test
      showed denervation hypersensitivity. Additionally pupils showed hypersensitivity
      to 1.25% epinephrine. These results suggest that lesions were post-ganglionic
      afferent fibers in both cardiovascular and pupillary systems. Administration of
      corticosteroid hormone resulted in dramatic improvement of his clinical symptoms
      including autonomic dysfunctions. Circulation disorder or infiltration of the
      inflammatory cells to the autonomic nervous system may be the cause of these
      dysfunctions in this patient.

PMID- 11577419
TI  - [Guillain-barre syndrome associated Campylobacter jejuni serotype Penner 2: a
      case report].
AB  - We described a 15-year-old male who had Guillain-Barre syndrome(GBS). Nine days
      after watery diarrhea, the patient developed pain and weakness of foot muscles.
      On admission, the nerve conduction studies revealed peripheral neuropathy with
      axonal degeneration and demyelination. Campylobacter jejuni(C. jejuni) with
      serotype of Lior 4, Penner 2 was isolated from his stool culture. IgM anti-GM 1
      antibody and other various anti-ganglioside antibodies were detected in his
      serum. After receiving plasma exchange and intravenous immunoglobulin therapy, he
      was able to walk without assistance. In general, C. jejuni with the serotype
      Penner 19 has been isolated from many GBS patients. In this patient, C. jejuni
      with the serotype of Penner 2 was isolated. The serotype is detected commonly in
      Miller Fisher syndrome.

PMID- 11577420
TI  - [A high aged case of herpes simplex viral encephalitis associated with
      progressive cerebral white matter lesion].
AB  - An 80-year-old male without abnormal past medical history presented with coma,
      general seizures, and fever subsequent to abnormal behavior. The pressure of the
      cerebrospinal fluid(CSF) elevated(13.5-20.5 cm H2O), and CSF examination revealed
      pleocytosis with predominant mononuclear cells(80-879/mm3) and elevated protein
      level(32-130 mg/dl). DNAs of herpes simplex virus(HSV) type 1 and 2 in CSF were
      not confirmed by polymerase chain reaction method in the acute phase. The
      HSV(type 1) antibody(HSV-1 Ab) ratio of serum to CSF(= [serum HSV-1 Ab]/[CSF HSV
      1 Ab]) was 0.98 and HSV-1 Ab index(= [CSF HSV-1 Ab]/[serum HSV-1 Ab] divided by
      [CSF albumin]/[serum albumin]) was 62.4. Initial fluid attenuated inversion
      recovery(FLAIR) (TR/TE/TI = 6,882/110/1,700 msec) axial magnetic resonance(MR)
      imaging showed hyperintensity in the subfrontal area, inferomedial portions of
      the temporal lobes, cingulate gyri, and insular cortices bilaterally.
      Meningoencephalitis caused by HSV-1 was diagnosed based on the values of HSV-1 Ab
      ratio of serum to CSF(less than 20), of HSV-1 Ab index(larger than 1.91), and the
      findings of MR imaging. Diffuse white matter lesions manifesting hyperintensity
      on FLAIR imaging in the bilateral frontal and temporal lobes close to the
      affected cortices developed approximately six weeks after the onset despite
      administration of antiviral agent and steroid. The lesion extensively involved
      the white matter of the bilateral frontal and temporal lobes finally. The initial
      value of myelin basic protein(MBP) in CSF was 0.9 ng/ml (normal value: less than
      4 ng/ml). Subsequent measurement of MBP in CSF about two, six weeks, two, three,
      and six months after the onset showed a marked increase of 233.9 ng/ml followed
      by a gradual decrease of 25.4 ng/ml, 18.4 ng/ml, 7.4 ng/ml and 4.3 ng/ml,
      respectively. Therefore, demyelination of the lesion in the cerebral white matter
      was suggested by the chronological change in FLAIR imaging and MBP in CSF.

PMID- 11577421
TI  - [Congestive heart failure caused by the thyroid stimulating hormone(TSH)
      secreting pituitary adenoma: report of two cases].
AB  - A 42-year-old man and a 31-year-old man with congestive heart failure caused by
      the thyroid stimulating hormone(TSH) secreting pituitary adenoma were reported.
      Heart failure was improved after transsphenoidal resection of the pituitary
      adenoma in each patient. The syndrome of inappropriate secretion of TSH causes
      hyperthyroidism. Thyroid hormone acts directly on cardiac muscle to increase the
      stroke volume. Hyperthyroidism itself reduces the peripheral vascular resistance
      and an elevated basal metabolism which is the basic physiologic change in
      hyperthyroidism dilates small vessels and reduces vascular resistance. The
      reduced vascular resistance contributes to increase stroke volume. Thyroid
      hormone also acts directly on the cardiac pacemakers to be apt to cause
      tachycardiac atrial fibrillation. These mechanical changes in hyperthyroidism
      increase not only the cardiac output but also the venous return. The increased
      blood volume and the shortened ventricular filling time due to tachycardia result
      in congestive heart failure. TSH secreting pituitary adenoma is a rare tumor,
      however heart failure is common disease. TSH secreting pituitary adenoma should
      be taken into consideration in patients with heart failure. The presented cases
      were very enlightening to understand the relation between brain tumor and heart
      disease.

PMID- 11577422
TI  - [Multiple brain abscesses associated with Rendu-Osler-Weber disease: report of
      two cases].
AB  - Two cases of multiple brain abscesses associated with congenital pulmonary
      arteriovenous fistula are reported. A 57-year-old male with Rendu-Osler-Weber
      disease complicated by pulmonary arteriovenous fistula developed multiple brain
      abscesses in the right parietal region. He responded well to surgical drainage
      and antibiotic therapy, and the pulmonary arteriovenous fistula, located in the
      left lower lobe, was resected. A 26-year-old female with Rendu-Osler-Weber
      disease complicated by pulmonary arterivenous fistula developed recurrent
      multiple brain abscesses in both the frontal and right parietal regions. The
      brain abscesses were successfully treated with aspiration and antibiotic therapy.
      She had a history of two previous brain abscesses in the right parietal regions
      that were excised on separate occasions at 16 and 23 years of age. Although
      pulmonary arteriovenous fistula was confirmed by angiography, in this case
      surgical removal of the pulmonary lesions was not indicated due to multiple
      vascular shunting. The patient had no recurrence of brain abscess with oral
      antibiotic therapy.

PMID- 11577423
TI  - [A case of corticobasal degeneration of which movemental disturbances were
      improved by administration of amantadine].
AB  - Corticobasal degeneration(CBD) is a neurodegenerative disorder characterised
      clinically by apraxia, cortical sensory loss, alien limb, dementia, oculomotor
      abnormalities, dysarthria, postural instability, akinesia, rigidity, and
      pyramidal signs. Brain imaging may demonstrate greater abnormalities
      contralateral to the more affected side. We reported a case of corticobasal
      degeneration of which praxic impairments were improved by administration of
      amantadine. The patient was a 63-year-old right-handed woman. She showed marked
      dysfunction including rigidity, limb kinetic apraxia, cortical sensory loss,
      ideomotor apraxia, and dressing apraxia. A brain MRI scan revealed bilateral
      cortical atrophy centered in the postcentral gyrus, more pronounced in the left
      hemisphere than the right. A SPECT scan showed a decrease in blood flow in the
      temporo-parieto-occipital regions, more pronounced in the left hemisphere than
      the right. An EEG showed a diffuse slowness. L-dopa had no effect on the symptoms
      of rigidity, limb kinetic apraxia, cortical sensory loss, ideomotor apraxia, and
      dressing apraxia. By administration of amantadine, rigidity and cortical sensory
      loss did not improve, but some praxic impairments, such as dressing apraxia and
      ideomotor apraxia, and the EEG improved. Upon withdrawal of amantadine, the
      improved symptoms deteriorated. Amitriptyline did not improve the deteriorated
      symptoms. After amantadine was re-administered, the same praxic impairments and
      the EEG improved again. This suggested that administration of amantadine had some
      effect on certain praxic impairments and the EEG.

PMID- 11577424
TI  - [MR image of an epidermoid tumor in the cerebellopontine angle: the usefulness of
      MRI FLAIR].

PMID- 11577425
TI  - [High signal intensity area in bilateral globus pallidus on T1-weighted image
      after manganese administration].

PMID- 11577426
TI  - [Radiation therapy for prostate cancer].
AB  - In Japan, where the mortality rate of prostate cancer is lower than in Western
      countries, radical prostatectomy or hormonal therapy has been applied more
      frequently than radiation therapy. However, the number of patients with prostate
      cancer has been increasing recently and the importance of radiation therapy has
      rapidly been recognized. Although there have been no randomized trials, results
      from several institutions in Western countries suggest that similar results of
      cancer control are achieved with either radiation therapy or radical
      prostatectomy. For higher-risk cases, conformal high-dose therapy or adjuvant
      hormonal therapy is more appropriate. In this article, the results of radiation
      therapy for prostate cancer were reviewed, with a view to the appropriate choice
      of therapy in Japan.

PMID- 11577427
TI  - [The role of radiologists in hospitals].

PMID- 11577428
TI  - [Present state of radiology in USA].

PMID- 11577429
TI  - [Director of hospital expect radiologist to do...].

PMID- 11577430
TI  - [Health economics in radiology].

PMID- 11577431
TI  - [The importance of radiology in medical malpractice legislation].

PMID- 11577432
TI  - [The future of radiotherapy, from a government perspective].

PMID- 11577433
TI  - [Multislice CT of the thorax: effects of contrast material pushed with saline
      solution using a dual power injector on contrast material dose and perivenous
      artifacts].
AB  - A new method of power injection of contrast material flushed with saline solution
      for thoracic multislice CT using a dual power injector was evaluated in 105
      patients. The patients were categorized into 3 groups of 35 patients each,
      according to the protocol of contrast material administration: (1) 100 mL of non
      ionic contrast material(300 mgI/mL), (2) 75 mL of the same contrast material, and
      (3) 75 mL of the same contrast material flushed with 30 mL of saline solution.
      Scanning was performed in a caudal-to-cranial direction. Mean attenuation for the
      three protocols was measured in the superior vena cava, pulmonary trunk,
      ascending aorta, and descending aorta. Vascular opacification and perivenous
      artifacts were graded using four-point scoring by a consensus panel of three
      blinded radiologists. Intravenous injection of 75 mL of contrast material flushed
      with saline solution provided significantly better vascular opacification in the
      superior vena cava(p < 0.001) and pulmonary trunk(p < 0.02) than that provided by
      a 75 mL or 100 mL injection of contrast material alone. A similar degree of
      enhancement was observed in the ascending and descending aorta. Further,
      perivenous artifacts in the subclavian vein were significantly reduced (p <
      0.05).

PMID- 11577434
TI  - [Fetal MRI: value and limitations--a review of 55 lesions].
AB  - OBJECTIVE: This study was undertaken to evaluate the usefulness and limitations
      of fetal MR imaging. MATERIALS AND METHODS: Fifty-five prenatal MRI examinations
      were performed, and the results were confirmed by postnatal follow-up or from
      pathological examination and clinical findings. All examinations were performed
      between 18 and 40 weeks of gestation without any premedication. A 1.5-Tesla
      superconductive MR imaging unit was used to obtain half-Fourier acquisition
      single-shot turbo spin-echo (HASTE) images. RESULTS: There were two false
      positive cases on US. MRI allowed the diagnosis of serious unsuspected lesions
      such as hypoplastic lung and anorectal malformation. MRI was also useful for the
      precise diagnosis of ventriculomegaly. However, MRI missed two cases of spinal
      dysraphism and one case of laryngotracheoesophageal cleft. CONCLUSION: Fetal MRI
      is a valuable complementary tool when prenatal US is inadequate or doubtful. MRI
      is useful for the evaluation of pulmonary hypoplasia or hydrocephalus and may
      modify obstetric management. MRI may be able to diagnose spinal dysraphism by
      detecting mild widening of the CSF space. However, MRI currently is not useful
      for making a differential diagnosis between laryngotracheoesophageal cleft and
      esophageal atresia.

PMID- 11577435
TI  - [Gadolinium-enhanced MR imaging, T2-weighted MR imaging, and transurethral
      ultrasonography].
AB  - PURPOSE: To assess the value and problems of dynamic gadolinium-enhanced MR
      imaging, T2-weighted MR imaging, and transurethral ultrasonography(TUUS) in
      staging of urinary bladder cancer. MATERIALS AND METHODS: Dynamic gadolinium
      enhanced MR imaging and FSE T2-weighted MR imaging of 64 patients with urinary
      bladder cancer who subsequently had surgery were retrospectively reviewed and
      compared with TUUS findings. RESULTS: Specificity for muscular invasion was 90.5%
      with TUUS, significantly better than with dynamic MR imaging (64.9%) (p < 0.05).
      The rates of overestimation of superficial cancer(pT1) with dynamic MRI and T2
      weighted MR imaging were 35.1%(13/37) and 24.3%(9/37), respectively. The staging
      accuracy of invasive cancer(pT2 or over) was 85.2% with dynamic MR imaging, which
      was better than the rate of 75.0% achieved with T2-weighted MR imaging.
      CONCLUSION: Although TUUS was a better modality for diagnosing superficial
      cancer(pT1), dynamic MR imaging was found to be better for diagnosing
      invasive(pT2 or over) cancer.

PMID- 11577436
TI  - [Whole-body MR imaging for evaluation of bone marrow cellularity in aplastic
      anemia].
AB  - The aim of this study was to investigate the usefulness of whole-body MRI(WB-MRI)
      in the evaluation of cellularity in bone marrow and the distribution of fatty
      marrow in aplastic anemia. WB-MRI was performed on five patients with aplastic
      anemia who ranged in age from 62 to 70 years of age, and on four controls with
      malignant lymphoma who ranged in age from 59 to 67 years. Coronal images were
      obtained using a body coil with an FOV of 48 cm x 48 cm, and with both fast short
      T1 inversion recovery(STIR) and spin-echo T1-weighted(T1-WI) in three regions:
      (1) head to thorax, (2) abdomen to pelvis, and (3) lower extremities. The
      findings on WB-MRI were compared with those of histological studies of bone
      marrow at the sternum and the posterior iliac crest. The results were as follows:
      (1) there was a correlation between the cellularity of histological studies of
      bone marrow and signal intensity on WB-MRI; (2) WB-MRI could detect the activity
      of bone marrow; and (3) in a comparison of signal intensity in aplastic anemia
      and control subjects, there were differences of signal intensity in the central
      marrow.

PMID- 11577437
TI  - Possible effects of endocrine disruptors on male reproductive function.
AB  - Endocrine disruptors act to alter blood hormone levels or the subsequent action
      of hormones, including effects on hormone production, release, transport,
      metabolism and/or elimination together with effects on cognate receptor binding
      and/or subsequent intracellular receptor actions. Confirmed alterations in
      reproductive development in wildlife species together with reports touting an
      increase in the incidence of human male reproductive tract abnormalities and
      decreased adult sperm counts in some parts of the world have increased public
      concern with endocrine disruptors. A biological plausible hypothesis has
      suggested that man-made chemicals act as endocrine disruptors resulting in
      altered development of the reproductive tract causing the observed effects. Based
      on current knowledge, the impact of endocrine disruptors on the male reproductive
      function remains to be appreciated. Epidemiological human studies are necessary
      to fill in the gap in our knowledge. Disturbances of hormonal regulation during
      fetal or postnatal development in humans may induce adverse effects on the male
      reproductive system, but these adverse effects of endocrine disruptors on humans
      are subtle, and difficult to research and detect. We have investigated fetal
      exposure to endocrine disruptors in Japan by analyzing umbilical cords, and
      changes of testis-weight in Japanese men by using analytical data of necropsy.
      This mini-review summarizes current endocrine disruptor issues on possible
      effects of endocrine disruptors on male reproductive function and the results of
      our recent research.

PMID- 11577438
TI  - Genetic characteristics of double hypoglossal canal as a nonmetric trait.
AB  - The hypothesis that the hypoglossal canal bridging or double (HGCD), a nonmetric
      cranial trait, is a powerful discriminator between populations (Dodo, 1980, 1987)
      is still controversial. To examine this issue, the incidences of HGCD were
      investigated in six inbred mice strains (CBA, C57BL, BALB/c, Strong A, NZB, and
      DAB) and one group of wild mice, six matings of CBA and C57BL, and four
      experimental diet groups. The above hypothesis was supported by some results such
      as no effects of diet on the incidences of HGCD and significant differences among
      the incidences of HGCD in some inbred strains. However, significant differences
      were also detected in the incidences of HGCD among groups within an inbred
      strain. Therefore, we think that further conservative and experimental
      assessments should be performed to determine the usefulness of incidences of HGCD
      as a powerful discriminator in skeletal studies on populations and family
      history.

PMID- 11577439
TI  - Scanning electron microscopic observation of Merkel cells in the lamprey
      epidermis.
AB  - The Merkel cell in the epidermis has generally been regarded as a mechanoreceptor
      which detects tissue deformations with its microvilli, and subsequently releases
      certain transmitters to nerve endings. In order to analyze the mechanism of
      mechanoreception, the fine structure of lamprey Merkel cells and their
      relationships with surrounding tissue were examined by scanning electron
      microscopy (SEM) after exposure of the cells by NaOH maceration, as well as by
      transmission electron microscopy (TEM) according to a conventional method. By
      SEM, lamprey Merkel cells revealed small round cell bodies bearing numerous
      microvilli on the upper and lower poles in accord with previous TEM reports.
      Combined SEM and TEM observations showed that the Merkel cell bodies were tightly
      held in corresponding concavities of other epidermal cells, with some desmosomes
      connecting the cells with each other. On the other hand, microvilli of the Merkel
      cells extended freely in intercellular spaces bound with complex microplicae of
      epidermal cells. The regional difference in mechanical anchorage of the Merkel
      cells probably leads to transient deflection and subsequent recovery of their
      microvilli during a given mechanical stimulation, suggesting rapidly adapting
      mechanoreception by the cells.

PMID- 11577440
TI  - [Distribution of 5'-nucleotidase activity in greater omentum of rats].
AB  - The aim of the present study is to demonstrate the cellular basis of 5'
      nucleotidase (5'-Nase) activity in the greater omentum of rats. Enzyme
      histochemistry for 5'-Nase showed that lymphatic vessels in the omentum as well
      as lymphocytes in the milky spots were positively stained. Electron microscopic
      observation revealed-5'-Nase activity at the luminal surface of the lymphatic
      endothelial cells, pinocytotic vesicles in the endothelial cells and the surface
      of fibroblasts located at the intercellular space of adipose cells. Fibroblasts
      extended long cytoplasmic processes toward adipose cells and inflammatory cells.
      These findings suggest that lymphatic endothelial cells as well as fibroblasts in
      the omentum may play an important role in regulation of metabolism and immune
      mechanisms in the greater omentum by supplying adenosin.

PMID- 11577441
TI  - [Keratin filaments in epithelial cells of the excretory ducts of rabbit
      submandibular glands--an immunohistochemical and ultraimmunohistochemical study].
AB  - To clarify the roles of various keratin proteins, the distributions of eight
      keratin intermediate filament proteins (keratins 7, 8, 10, 13, 14, 18, 19 and 20)
      in the epithelial cells of the excretory ducts of rabbit submandibular glands
      were studied immunohistochemically and ultraimmunohistochemically. The epithelia
      of excretory ducts were composed of columnar cells and basal cells. In the
      columnar cells, intermediate filaments formed a network at the apical area, that
      is, an apex network connected with desmosomes. Keratins 7, 18 and 20 were
      detected in the upper layer of the network and keratins 8, 18 and 20 in the lower
      layer. The intermediate filaments containing keratin 7 were also connected with
      hemidesmosomes on the basal side. Keratins 7, 18 and 20 were found throughout the
      entire cytoplasm of the columnar cells. Keratins 8 and 14 were expressed near the
      nucleus, forming a ring-like structure around the Golgi apparatus in the columnar
      cells. In the basal cells, by contrast, the intermediate filaments were
      concentrated around the nucleus, forming a juxtanuclear network which contained
      keratin 10. Keratin 13 was detected between the juxtanuclear network and the cell
      membrane, and was connected with both desmosomes and hemidesmosomes. Kratin 7
      filaments were contained throughout the entire cytoplasm of the basal cells.
      These results suggested that different functional subsets of keratin filaments
      could be distinguished in the epithelial cells of the excretory ducts of the
      submandibular glands. In the columnar cells, keratins 7, 8, 18 and 20 play a role
      in cell-cell contact or cell-matrix contact, and both keratins 8 and 14 seem to
      be involved in the structure of the Golgi apparatus. In the basal cells, keratin
      10 may serve to position and anchor the nucleus within the cell, and keratin 13
      plays a role in cell-cell and cell-matrix contacts.

PMID- 11577442
TI  - [An anomalous case of the thoracic cardiac nerve in the Japanese monkey].
AB  - A rare case of an anomalous right thoracic cardiac nerve that directly
      distributed to the left ventricle and left coronary artery was observed in a
      Japanese monkey. Its nerve arose from 4th and 5th thoracic ganglia on the right
      sympathetic trunk, descended obliquely along the thoracic vertebra toward the
      thoracic aorta at the level of the body of 7th thoracic vertebra. After reaching
      the aorta, it reflected upward and ascended along the medial-ventral surface of
      the aorta. Thereafter, it received a cardiac branch arising from the vagus nerve
      in the upper part of the thoracic aorta, and ran to the left-lateral aspect of
      the heart. Finally, it gave off main branches to the terminal part of the left
      coronary artery and the left ventricle, and small branches to the proximal part
      of the left coronary artery. In a human dissection, similar nerves (the thoracic
      splanchnic nerve or thoracic pulmonary nerve) originating at the thoracic ganglia
      and reaching to the lung, have also been observed. The superior, middle and
      inferior cervical cardiac nerves can easily reach the heart along the common
      carotid artery, the brachiocephalic artery and subclavian artery. But it is not
      easy for the thoracic cardiac nerve to reach the heart because of the
      topographical relationship of its thoracic origin and the peripheral
      distributions of the left side of the heart. Therefore, the thoracic cardiac
      nerve would have to run a complicated course.

PMID- 11577443
TI  - [Considerable supplement on the central cusp in the lower second molar].
AB  - The central cusp, one of morphological anomalies of tooth, is a supernumerary
      tubercle found principally in the center of the occlusal surface of a molar. Most
      central cusps reported are observed in the premolar, but very few studies are
      available on the central cusp in molar, especially in the lower second molar. In
      the present study, the central cusp on either side of the lower second molar were
      reported and discussed according to the previous investigation as a supplement on
      this subject.

PMID- 11577444
TI  - Molecular biological markers and micrometastasis in resected non-small-cell lung
      cancer. Prognostic implications.
AB  - OBJECTIVES: Recent advances in molecular biology and genetics have created new
      diagnostic and treatment possibilities in clinical oncology. We evaluated the
      usefulness of molecular biological factors in primary tumor and micrometastasis
      in the bone marrow and pathological negative (pN0) lymph nodes as prognostic
      parameters in non-small-cell lung cancer (NSCLC) patients. METHODS: Pathological
      specimens were collected from 129 NSCLC patients to analyze molecular biological
      markers, including K-ras, p53, Rb, p16, loss of heterozygosity (LOH) at 3p,
      vascular endothelial growth factor (VEGF), and telomerase activity. Bone marrow
      samples from 250 NSCLC patients and pN0 lymph nodes from 85 of these patients
      were collected for micrometastasis detection by immunohistochemistry against
      cytokeratin. RESULTS: p53 abnormalities and 3p LOH were significantly associated
      with reduced patient survival in adenocarcinoma, whereas VEGF expression was
      significantly associated with reduced survival in a squamous cell carcinoma
      histological subtype by univariate or multivariate analysis. We identified
      micrometastatic tumor cells in bone marrow of 78 (31.2%) of 250 patients and in
      pN0 lymph nodes of 26 (30.6%) of 85 patients. Both bone marrow and lymph nodal
      micrometastases were associated with decreased survival among patients with stage
      I, however, only lymph nodal micrometastasis had a significant impact on
      survival. CONCLUSIONS: Molecular biological features of primary tumor and
      micrometastatic status appear useful in defining groups of patients with a poor
      prognosis who could benefit from adjuvant systemic treatment.

PMID- 11577445
TI  - Lung volume reduction surgery and nutritional status in patients with severe
      emphysema.
AB  - OBJECTIVE: We studied the short-term effect of lung volume reduction surgery on
      nutritional status including body composition and the relationship between
      preoperative nutritional status and postoperative morbidity. METHODS: Subjects
      were 28 patients with emphysema who underwent bilateral thoracoscopic lung volume
      reduction surgery (23 simultaneously, 5 staged). Functional tests, body weight,
      and body composition were measured before and 6 months after surgery. Fat-free
      mass and fat mass were assessed by bioelectrical impedance analysis. RESULTS:
      FEV1.0 improved 35.2% following surgery and maximal oxygen uptake 23.8%. Body
      weight and fat-free mass increased significantly after surgery, while fat mass
      was unchanged. Of the 23 undergoing simultaneous bilateral lung volume reduction
      surgery, 8 had major complications-3 required additional surgery to close air
      leaks, 3 required mechanical ventilation (> 72 hrs), and 2 developed
      postoperative infection. The preoperative percentage of ideal body weight and fat
      free mass was significantly higher among patients without major complications.
      CONCLUSIONS: Bilateral lung volume reduction surgery increases fat-free mass and
      provides functional improvement for underweight patients with severe emphysema.
      We found fat-free mass and body weight to be good predictors of unacceptable
      postoperative complications following bilateral lung volume reduction surgery.

PMID- 11577446
TI  - Risk stratification analysis of operative mortality in coronary artery bypass
      surgery.
AB  - OBJECTIVE: We assessed the operative mortality of coronary artery bypass grafting
      (CABG) surgery using risk stratification. METHODS: In 294 consecutive patients
      who underwent CABG with or without concomitant surgery from August 1994 to
      December 1999, we compared operative mortality calculated conventionally and by
      risk stratification. Scores for each patient were calculated using the Parsonnet
      additive model and stratified based on the probability of operative mortality.
      RESULTS: Overall crude hospital mortality was 4.8%-4.0% among patients younger
      than 80 years and 14% among those 80 years of age or older (p = 0.0692). Hospital
      mortality was 12% in urgent/emergency surgery, and 1.5% in elective surgery (p <
      0.0002), and 4.5% in CABG alone and 7.4% in CABG with concomitant surgery (p =
      0.3763), and 25% in patients receiving vein grafts only and 3.0% in those
      receiving at least 1 artery graft (p = 0.0003). Overall patient distribution was
      32% good, 20% fair, 20% poor, 11% high-risk, and 16% extremely high-risk.
      Predicted mortality was 2.2% for patients who were a good risk, 6.7% for fair
      risk, 12% for poor-risk, 16% for high-risk, and 25% for extremely high-risk
      patients. Actual operative mortality was 1.0% for good-risk, 0% for fair-risk,
      3.4% for poor-risk, 6.3% for high-risk, and 18% for extremely high-risk patients,
      making actual mortality significantly lower than that predicted. CONCLUSION:
      Comparing predicted mortality and actual mortality enabled us to objectively
      calculate operative results and assess operative quality.

PMID- 11577447
TI  - Risk factors reducing blood transfusion requirements in pediatric open heart
      surgery after introduction of vacuum assisted circuits.
AB  - OBJECTIVES: Open heart surgery without homologous blood transfusion remains
      difficult in children. The introduction of vacuum-assisted cardiopulmonary bypass
      circuits to reduce priming volume for pediatric patients has improved the
      percentage of transfusion-free operations. We retrospectively analyzed blood
      transfusion risk factors to further reduce blood transfusion requirements after
      vacuum-assisted circuit introduction. METHODS: From March 1995 to June 1996, 49
      patients weighing between 5 and 20 kg underwent cardiac surgery with
      cardiopulmonary bypass at our institution, excluding hospital deaths. We
      retrospectively analyzed risk factors influencing blood use in 37 patients with
      no blood priming in cardiopulmonary bypass after introducing a vacuum-assisted
      system. Factors selected for univariate analysis were age, body weight, cyanosis,
      preoperative Hb, operation time, cardiopulmonary bypass time, aortic cross
      clamping time, and intraoperative and postoperative bleeding volume. Correlation
      between total bleeding volume/body weight and cardiopulmonary bypass time was
      studied by regression analysis. RESULTS: As risk factors, univariate analysis
      identified cyanotic disease, longer operation time (> 210 minutes), longer
      cardiopulmonary bypass time (> 90 minutes), longer aortic cross-clamping time (>
      45 minutes), greater intraoperative bleeding volume/body weight (> 4 ml/kg), and
      greater postoperative bleeding volume/body weight (> 15 ml/kg). Regression
      analysis showed a significant positive correlation between total bleeding
      volume/body weight and cardiopulmonary bypass time. CONCLUSIONS: Cyanotic disease
      and long bypass time are risk factors in reducing blood transfusion requirements
      in pediatric open heart surgery after introduction of vacuum-assisted circuits.
      Further efforts are needed, however, to reduce blood transfusion requirements,
      particularly in these children.

PMID- 11577448
TI  - Effects of gene transfection of human bcl-2 on concordant cardiac xenografts in
      hamster to rat model.
AB  - OBJECTIVES: Concordant cardiac xenografts are known for delayed vascular
      rejection. Therapy combining with FK506 and cobra venom factor prolongs graft
      survival. The proposed underlying mechanism holds that cytoprotective proteins
      such as Bcl-2 play a role here. We studied the effects of gene transfection of
      human-bcl-2 on graft survival and coronary artery lesions in concordant cardiac
      xenografts, and discuss the role of cytoprotective genes in vascular xenograft
      rejection. METHODS: Golden-Syrian-hamster hearts were heterotopically
      transplanted into Lewis rats given FK506 (1 mg/kg daily) and cobra venom factor
      (0.2 mg/kg; day 0 and 1) intramuscularly. They were divided into 2 groups--grafts
      transfected vector with the human-bcl-2 gene (Group-B(+)) and vector without the
      gene (Group-B(-)) using the HVJ liposome method; 4 or 5 grafts from each group
      were explanted 1, 2, 3, or 4 weeks and more than 1 month after transplantation
      and evaluated by H-E, Elastic-Van-Gieson and immunohistochemical staining of Bcl
      2. Coronary arterial lesions were examined using a scoring method. RESULTS: Bcl-2
      expression in endothelial cells in Group-B(+) was confirmed within 2 weeks after
      transplantation but not thereafter. The coronary score in Group-B(+) was
      significantly lower than that in Group-B(-) within 2 weeks after transplantation
      but not thereafter. CONCLUSIONS: In this hamster-to-rat cardiac xenograft model,
      the bcl-2 gene was successfully transfected to the coronary endothelium and
      lasted 2 weeks. During Bcl-2 expression, coronary vascular lesions were
      suppressed more than in the untransfected group.

PMID- 11577449
TI  - Combined resection of distal aortic arch for T4N0 non-small-cell lung cancer with
      aortic arch invasion.
AB  - Three men age: 39-51 years (mean: 43.3 years) with T4N0 lung cancer infiltrating
      the distal aortic arch underwent combined resection of the left upper lobe,
      distal aortic arch, and left subclavian artery using partial extracorponeal
      circulation. Selective cerebral perfusion was used in 2. One underwent induction
      therapy (CDDP + VP - 16 x 2 + radiation 30 Gy), and all underwent adjuvant
      therapy. No postoperative complications or postoperative death occurred. Average
      ICU stay was 2.3 days. All patients are alive without local recurrence. Two were
      disease-free 37 and 26 months after surgery, and 1 had adrenal gland metastasis 8
      months after surgery. Extended resection of the aortic arch in lung cancer is
      thus feasible and worthwhile in patients with T4N0 non-small-cell lung cancer.

PMID- 11577450
TI  - Ruptured left ventricular pseudoaneurysm penetrating into the left pleural
      cavity.
AB  - We experienced a rare case of ruptured left ventricular pseudoaneurysm
      penetrating into the left pleural cavity. A 77-year-old woman was first diagnosed
      with unstable angina due to sudden chest pain onset and abnormal
      electrocardiographic findings. In 2 days, massive left pleural effusion was
      recognized by chest X-ray, though subsequent computed tomographic scans did not
      show any aortic pathology. We observed her with left thoracentesis alone. Two
      days later, cardiac arrest suddenly occurred and emergency surgery was undertaken
      after resuscitation by percutaneous cardiopulmonary support. In surgery, a
      moderate amount of intrapericardial hematoma caused by rupture of a left
      ventricular pseudoaneurysm penetrating into the left pleural cavity was found and
      successfully repaired. This rare rupture of a left ventricular pseudoaneurysm
      penetrating into the left pleural cavity generated massive hemo-hydrothorax.

PMID- 11577451
TI  - Acute aortic dissection associated with Sheehan's syndrome.
AB  - A 69-year-old woman with Sheehan's syndrome who suffered acute Stanford type A
      aortic dissection had received corticosteroids and thyroid hormones for over 20
      years. The entire ascending aorta was replaced in emergency graft replacement. We
      administered twice the usual dose of methylprednisolone during cardiopulmonary
      bypass and twice the patient's usual dose of prednisolone from postoperative day
      1 to 6. The usual 100 micrograms of levothyroxine sodium was given orally from
      postoperative day 1. The patient's postoperative course was uneventful. This case
      emphasizes the importance of early active supplementary treatment with steroids
      and thyroid hormones for major surgery in patients with Sheehan's syndrome.

PMID- 11577452
TI  - Reoperative minimally invasive axillocoronary artery bypass to the obtuse
      marginal branch.
AB  - A 73-year-old man was admitted with unstable angina, having severe coronary
      artery disease involving 3 vessels. He had undergone coronary artery bypass
      grafting to the left anterior descending artery and the obtuse marginal branch
      using saphenous vein grafts in 1979. Computed tomography showed severe calcium
      deposition and atherosclerosis in the ascending and descending aorta. We
      conducted axillocoronary artery bypass to the obtuse marginal branch and left
      internal thoracic artery as an in situ graft to the left anterior descending
      artery without cardiopulmonary bypass. Grafts were satisfactory and clinical
      results good.

PMID- 11577453
TI  - Pedunculated hemangioma in the right ventricle.
AB  - We report a rare case of right ventricular hemangioma. In an asymptomatic 56-year
      old man, echocardiography as a part of medical checkup demonstrated a
      pedunculated tumor, 1.0 x 1.3 x 1.5 cm, arising from the free wall of the right
      ventricle. No findings were seen of a feeding artery to the tumor or vascular
      blush in preoperative coronary angiography. Successful resection was done through
      right atriotomy under total cardiopulmonary bypass. The histological examination
      revealed capillary hemangioma. The postoperative clinical course was uneventful,
      but requires careful follow-up for possible coronary cardiac fistula. This is the
      fifth case of right ventricular hemangioma, to our knowledge, ever reported in
      Japan.

PMID- 11577454
TI  - Platelet activation and aggregation during normothermic cardiopulmonary bypass.

PMID- 11577455
TI  - [Molecular mechanisms of calcium regulation of striated muscle contraction and
      its genetic disorder].
AB  - Contraction of skeletal and cardiac muscles is regulated by Ca2+ through a
      specific Ca(2+)-receptive protein, troponin, regularly distributed along the thin
      filaments. This protein consists of three different subunits, troponins C, I and
      T. In this article, studies on the structural and biochemical aspects of the
      molecular mechanisms of Ca(2+)-regulation were first reviewed with particular
      reference to the regulatory role of troponin T. Several properties of the
      isoforms of troponin from fast and slow skeletal and cardiac muscles were
      discussed, based on the findings obtained by the use of troponin-exchange
      techniques under physiological conditions. Recent findings on the functional
      consequence of mutations in human cardiac troponins T and I found in familial
      hypertrophic cardiomyopathy were also presented. The results clarified the
      increase in Ca(2+)-sensitivity of contraction to be the critical consequence due
      to this genetic disorder.

PMID- 11577456
TI  - [Studies on histamine with L-histidine decarboxylase, a histamine-forming enzyme,
      as a probe: from purification to gene knockout].
AB  - I have been studying the functions of the histaminergic neuron system in the
      brain, the location and distribution of which we elucidated with antibody raised
      against L-histidine decarboxylase (a histamine-forming enzyme) as a marker in
      1984. For this purpose, we used two methods employing (1) pharmacological agents
      like alpha-fluoromethylhistidine, an HDC inhibitor, and agonists and antagonists
      of H1, H2 and H3 receptors and (2) knockout mice of the HDC- and H1- and H2
      receptor genes. In some cases, we used positron emission tomography (PET) of H1
      receptors in living human brains. It turned out that histamine neurons are
      involved in many brain functions, and particularly, histamine is one of the
      neuron systems to keep awakefulness. Histamine also plays important roles in
      bioprotection against various noxious or unfavorable stimuli (convulsion,
      nociception, drug sensitization, ischemic lesions, stress and so on). Finally, I
      briefly described interesting phenotypes found in peripheral tissues of HDC-KO
      mice; the most striking finding is that mast cells in HDC-KO mice are fewer in
      number, smaller in size and less dense in granule density than those of wild type
      mice, indicating that histamine is related to the proliferation and
      differentiation of mast cells. In conclusion, histamine is important not only in
      the central and peripheral systems as studied so far but also may be related to
      some new functions that are now under investigation in our laboratories.

PMID- 11577457
TI  - [New strategy on medical research after completion of genome sequencing].
AB  - Real advances in biotechnology made it possible to complete human whole genome
      sequencing within a short duration. Although the genome includes a huge amount of
      information about biological functions and the interest is now directed to the
      study using genomic information, the genomic strategy is not clearly understood.
      The following 4 studies were therefore presented and discussed about the strategy
      after the completion of the genomic sequence in the 74th Annual Meeting of
      Japanese Pharmacological Society: 1) Asthma and atopic dermatitis: models for
      genetic and genomic investigations of complex genetic diseases, by W.C.O. Cookson
      (University of Oxford, Asthma Genetics Group, Wellcome Trust Centre for Human
      Genetics); 2) Molecular classification by global gene expression profiling:
      application on oncogenomic research, by H. Aburatani (Genome Science Division,
      Research Center for Advanced Science and Technology, University of Tokyo); 3)
      Functional genomic search of disease-related genes using microarrays with
      normalized rat cDNA library, by G. Tsujimoto, et al. (Department of Molecular,
      Cell Pharmacology, National Children's Medical Research Center: and 4) Acute
      ischemic change of mRNA expression in the hippocampus by GeneChip array analysis:
      a starting point for post-genome strategy, by S. Asai, et al.

PMID- 11577458
TI  - [Activation of ATP-sensitive K+ channels by ADP and K+ channel openers: homology
      model of sulfonylurea receptor carboxyl-termini].
AB  - The ATP-sensitive K+ channels (KATP) are composed of Kir6.0 subunits and
      sulfonylurea receptors (SUR1, 2A and 2B). SUR2A and SUR2B are splice variants and
      differ only in the C-terminal 42 amino acid residue (C42). SURs are supposed to
      be the subunit that determines the different response of KATPs to intracellular
      nucleotides, K+ channel openers and inhibitors. In this study, we report that C42
      of SURs plays critical roles in differential activation of various KATPs by ADP
      and K+ channel openers such as diazoxide and nicorandil. KATPs containing
      distinct SURs and Kir6.2 were reconstructed on HEK293T cells. Much higher
      concentrations of ADP were necessary to activate channels which SUR1 or SUR2B. In
      all KATPs containing different SUR, diazoxide increased the potency of ADP for
      channel activity without affecting its efficacy. From the electrophysiological
      data obtained from C-terminal chimeras and point mutants in the second nucleotide
      binding domain (NBDs), we developed the homology model of each SUR-NBD2 based on
      the crystallgraphically determined structure of HisP, a member of the ABC protein
      superfamily. In this model, C42 is located just beneath the Walker A motif of
      NBD2 and regulates the binding of nucleotide to NBD2 by affecting the 3-D
      construct of NBD2. This homology model well explains the different response of
      KATPs to ADP. Based on this model, it will be possible to develop new ligands for
      KATPs.

PMID- 11577459
TI  - [High throughput pharmacology for drug discovery].
AB  - High Throughput Screening (HTS) now plays an important role in the discovery of
      new lead compounds for novel therapeutic targets. The advantage of HTS over the
      conventional method, now termed as Low Throughput Screening (LTS), is that
      valuable compounds can be selected rapidly from a large number of samples with
      minimal human involvement. In spite of the growing awareness of HTS, the
      importance of the LTS in the drug discovery and development is still not changed.
      Advances in pharmacogenomics will also provide us many pharmacological targets,
      and thus increase the number of compounds that should be assayed by HTS and LTS.
      In this review, we will first describe the outline of HTS. We will next describe
      new approaches to develop and brush up the LTS: 1) screening method of drugs
      acting on ion channels by voltage-sensitive fluorescent dye, 2) functional assay
      method using reconstituted smooth muscle fiber, and 3) organ culture method as a
      useful model of vascular proliferative disease. These approaches, which work
      cooperatively with HTS, will contribute greatly to the development of new drugs.

PMID- 11577460
TI  - [NF-kappa B as a therapeutic drug target].
AB  - The transcription factor NF-kappa B has attracted widespread interest based on
      its unusual regulation, the variety of stimuli that activate it, the diverse
      genes and biological responses that it controls, the striking evolutionary
      conservation of structure and function among family members, and its apparent
      involvement in a variety of human diseases. Recently NF-kappa B has been shown to
      be the target of new drug discovery. Here, we discuss the so-called NF-kappa B
      inhibitors and consider the development of new therapeutic agents.

PMID- 11577461
TI  - [Bioassay for endocrine disruptors by using yeast two-hybrid system].
AB  - One of the urgent tasks in understanding endocrine disruptors (EDs) is to compile
      a list of suspected substances among the huge number of chemicals by using the
      screening test method. An in vitro screening test is a more useful tool for
      primary selection of suspected EDs. We have developed an assay for EDs using the
      yeast two-hybrid system. The assay is based on the ligand-dependent interaction
      of two proteins, a hormone receptor and a coactivator, and the hormonal activity
      is detected by beta-galactosidase activity. This assay is a very simple and
      inexpensive test method with high repeatability to detect the agonist, and it is
      applicable for the detection of antagonist and active compounds after metabolism.
      Accordingly, it has been used in more than 40 laboratories in Japan. To date, we
      have tested the estrogenic activity of more than 500 chemicals including natural
      substances, medicines, pesticides and industrial chemicals. Sixty-four compounds
      were evaluated as positive and most of these possessed a common structure: phenol
      with a hydrophobic moiety at the para-position without bulky groups at the ortho
      position. These results are expected to facilitate further risk assessment of
      chemicals, especially EDs.

PMID- 11577462
TI  - [Levofolinate and fluorouracil combination therapy].
AB  - Levofolinate and fluorouracil regimen (l-leucovorin and 5 fluorouracil regimen)
      is a biochemical modulation of 5 fluorouracil (5FU) by leucovorin (LV). In the
      USA and Europe d,l-LV and 5FU regimen is frequently administered for colorectal
      cancer treatment and recognized as the standard regimen. In Japan, multi
      institutional clinical trials of l-leucovorin (l-LV), a bioactive diastereomer of
      leucovorin, and 5FU combination were conducted for the treatment of advanced
      gastrointestinal cancer with comparable results to the US/Europe data. This l-LV
      and 5FU regimen was approved in August 1999 for the indications of advanced
      gastric cancer and colorectal cancer. The dosage and administration is referred
      to the weekly method developed at RPMI. Recently, the irinotecan (CPT-11) or
      oxariplatin plus LV and 5FU combination showed higher antitumor activities than
      the LV and 5FU combination with increased progression-free survival. These
      regimens, however, are not yet properly established because clinical trial
      results with Japanese patients are not completed for agreement of the dosage and
      administration schedule. For the l-LV and 5FU regimen diarrhea and
      leukocytopenia, including grade 3 and higher, were reported as the major adverse
      events. Administration for eligible patients with periodical monitoring of
      diagnostic data is necessary.

PMID- 11577463
TI  - [Cyclooxygenase (COX)-2 selective inhibitors: aspirin, a dual COX-1/COX-2
      inhibitor, to COX-2 selective inhibitors].
AB  - Aspirin was developed as a non-steroidal anti-inflammatory drug (NSAID) in 1899.
      During the century after that, aspirin has been found to show its anti
      inflammatory, analgesic and anti-pyretic activities by reducing prostaglandins
      biosynthesis through inhibition of cyclooxygenase (COX); and then COX was found
      to be constituted of two isoforms, constitutive COX-1 and inducible COX-2.
      Currently, novel NSAIDs, acting through selective inhibition of COX-2, that have
      efficacy as excellent as aspirin with significantly lower incidence of
      gastrointestinal adverse effects are available in America and some other
      countries, but not in Japan. Physiological and pathophysiological roles of COX-1
      and COX-2 have been explained from studies in experimental animals, but there are
      many differences in species and diseases between animals and humans. Thus,
      physiological and pathophysiological roles of COX-2 were considered from the
      standpoint of clinical effects of the two latest COX-2 selective inhibitors,
      celecoxib and rofecoxib, on inflammation, pain, fever and colorectal cancer
      together with their adverse effects on gastrointestinal, renal and platelet
      functions; and the usefulness and limits of COX-2-selective inhibitors were
      discussed with the trends of new NSAIDs development.

PMID- 11577464
TI  - [Effect of combined treatment with vitamin K2 and 1 alpha-(OH)-vitamin D3 on bone
      loss in ovariectomized rats].
AB  - Different types of therapeutic agents for osteoporosis are often simultaneously
      prescribed for the same patient, but limited experimental findings indicate the
      significance of combined treatment. In the present study, the inhibitory effect
      of combined vitamin K2(K2) and 1 alpha-(OH)-vitamin D3(D3) treatment on bone loss
      was compared to that of K2 or D3 alone in ovariectomized rats. Female rats (20
      week-old) were ovariectomized and divided into 4 groups as follows: they were
      treated for 8 weeks with vehicle, K2 (30 mg/kg), D3 (0.3 microgram/kg) and K2 and
      D3 (K2 + D3) at the respective doses. K2 was given as a dietary supplement and D3
      was orally administered 3 times a week. Bone density of the femurs was measured
      by peripheral quantitative computed tomography. Ovariectomy resulted in decreased
      bone density in proximal metaphysis, especially in the trabecular region, and
      treatment with K2, D3 or K2 + D3 inhibited this decrease. Moreover, in the K2 +
      D3 group, bone density and mineral content in the trabecular region in proximal
      metaphysis and cortical bone width in diaphysis were significantly higher than
      those in the D3 group. Consistent with these observations, bone strength in the
      femoral midshaft tended to increase only in the K2 + D3 group compared to that in
      the vehicle group. These findings indicate that combined K2 and D3 treatment is
      more effective for bone loss than that with K2 or D3 alone.

PMID- 11577465
TI  - [Completely an art].

PMID- 11577466
TI  - [Problems posed by the diagnosis and prenatal management of facial clefts].
AB  - OBJECTIVE: To identify the difficulties in relation to prenatal diagnosis of
      cleft lip and/or palate. To provide useful clue to the clinician in order to
      evaluate prognosis and for prenatal management of this malformation. PATIENTS AND
      METHODS: Retrospective study of all cases managed in our fetal medicine unit
      between January 1991 and December 1999. During this study period 64 cases of
      fetal cleft lip and/or palate were retrospectively reviewed. From June 1995, all
      cases were prospectively recorded, giving us the opportunity to compare the
      performance of three ultrasound signs for associated secondary cleft palate.
      RESULTS: The mean gestational age at diagnosis was 26 weeks. Associated
      ultrasound abnormalities were detected in 42% of cases. Chromosome analysis was
      performed in all fetuses with associated ultrasound findings and in 39% of
      fetuses with isolated facial clefts. All fetuses with isolated cleft were
      chromosomally normal, whereas 15 of the 26 with additional abnormalities had
      chromosomal defects. Prospective assessment of three ultrasound signs of
      associated secondary cleft palate was considered possible in 57% of facial
      clefts. Sensitivity of these signs was respectively 78% (interruption of the
      secondary palate midline linear echo in a sagittal view), 87% (abnormal oro
      nasopharyngeal fluid flow with color Doppler imaging) and 31% for ancillary signs
      (amniotic fluid excess and non-visualized fetal stomach) for the prediction of
      associated cleft palate. Only the absence of the three signs to rule out
      secondary cleft palate. CONCLUSION: Prenatal diagnosis of cleft lip and/or palate
      must draw attention to associated sonographic malformations. When cleft lip
      and/or palate is isolated, amniocentesis is recommended apart from selected
      cases. Secondary palate involvement is difficult to ascertain during pregnancy.

PMID- 11577467
TI  - [The growth of the maxilla in humans. What place for the premaxilla?].
AB  - INTRODUCTION: The growth of the maxilla in man is still debated. Many authors
      described an anterior part of the maxillary bone, called premaxilla distinct from
      the maxilla proper. This description referred to the existence in animals of an
      incisive or premaxillary bone which does not exist in man. Is this distinction
      pertinent in the human facial growth? MATERIAL AND METHODS: To settle this
      question, we performed a histologic study in eight embryos and fetuses aged from
      40 days to 10 weeks post conceptional (PC) and an anatomic dissection of 3
      palates of fetuses aged from 22 to 30 weeks PC. RESULTS: We found only one
      maxillary point of ossification, and the growth of the anterior part of the
      maxilla cannot be separated from the global growth of the maxilla. DISCUSSION:
      The independence of the anterior part of the maxilla in man is very limited
      during the growth and cannot justify the term of premaxilla.

PMID- 11577468
TI  - [Palatal aponeurosis and the insertion of the tensor muscle of the soft palate.
      An anatomic study and clinical applications].
AB  - INTRODUCTION: Knowledge of the anatomy of soft palate muscles is of great
      interest in cleft palate surgery, in surgical correction of obstructive sleep
      apnea syndrome and in excision of maxillo-facial carcinomas. Some authors
      described the palatal aponeurosis as the expansion of the tendon of the two
      tensor veli palatini muscles, others stated that the palatal aponeurosis is a
      distinct anatomic entity. METHOD: Ten dissections of the soft palate have been
      performed to improve our knowledge of its anatomy. RESULTS: The palatal
      aponeurosis is a distinct anatomic entity continuous with the periosteum of the
      nasal cavity. The tendon of the tensor veli palatini terminated on the inferior
      side of the aponeurosis. One fifth of the tensor's tendinous fibers terminated on
      the posterior border of the palatine bone and the others are spreading on the
      anterior and inferior side of the palatal aponeurosis. DISCUSSION: In cleft
      palate patients, this aponeurosis is absent, the palatal muscles are attached to
      the posterior border of the palatine bones. So it seems to be logical to
      recommend a soft-palate "pushback" to create a new space between the posterior
      border of the palatine bones and the soft-palate muscles.

PMID- 11577469
TI  - [Development of the maxilla in patients with complete unilateral cleft palate
      surgically treated by a periosteal transplantation technic. A retrospective study
      of 15 surgical cases with an 18 year follow-up].
AB  - PURPOSE: The aim of this study was to assess retrospectively the long-term growth
      of the maxilla in subjects with unilateral total cleft treated initially with the
      tibial periosteal graft technique. PATIENTS AND METHODS: The study group included
      15 patients with a mean 18 years follow-up (range 15-20 years). All patients had
      been operated on by the same surgeon. Only patients in stage DP3, one to two
      years after peak growth were retained for review. Delaire's architectural
      analysis was used to study anteroposterior and vertical growth of the maxilla.
      Transverse growth was studied with the Mars occlusal score. Bone generation
      induced by the periosteum was studied using the Bjork Holmgren analysis. The
      quality of the palatine and nasal repair was studied using Pruzansky's criteria.
      RESULTS: Anteroposterior and vertical growth led to a normal maxilla in 53.3% of
      the cases and a moderate to severe retromaxilla (> 5 mm) in 46.7%. Complete
      symmetry was achieved for the nasal fossae in 20% of the cases and marked
      asymmetry was noted in 26%. The height of the nasal fossae was symmetrical in 60%
      of the cases with marked asymmetry in 26%. Mean production of alveolar bone
      reached 58% of the height of the alveolar bone filling. It was good in 46.6% of
      the cases, fair in 26.7% and weak in 26.7%. The occlusal score evidenced crossed
      occlusion in 33.3% of the cases for a hemisection and in 46.7% of the cases for
      an anterior section. Normal occlusion was achieved in 20%. The quality of
      palatine repair was found to be good with a normal mucosa in 86.7% of the cases.
      A fistula was present in 13.3%. CONCLUSION: The preoperative objectives of
      periosteal graft repair of unilateral complete clefts were achieved. This
      technique provides a closed scar-free palate. Nasal repair favored the
      development of an ample and functional airway. The periosteal graft produced bone
      in the anterior portion allowing a harmonious premaxillary region and stable nose
      support.

PMID- 11577470
TI  - [Comment on "The development of the maxilla in patients with complete unilateral
      cleft palate surgically treated by a periosteal transplantation technic"].

PMID- 11577471
TI  - [The genetics of labio-palatal clefts].
AB  - Labial and/or palatine clefts are an interest in example of the interaction
      between genetic and environmental factors. The OFC1 gene, localized on 6p24.3
      would play a primary role in the development of labial and/or palatine clefts
      while the OFC2 (2p13), OFC3 (19p13.2) and RARA (17q21.1) would play a role in
      modifying genetic susceptibility. Different environmental, nutritional and toxic
      factors (alcohol, tobacco, drugs...) could also directly contribute one-third of
      these oral clefts. Identification of subjects at risk of having a child with
      labial and/or palatine cleft on the basis of both phenotypic and genotypic
      factors would be most helpful in recognizing environmental factors triggering
      their development, a first step towards prevention.

PMID- 11577472
TI  - [Bilateral labio-maxillo-palatal clefts. Therapeutic evaluation].
AB  - The wide diversity of bilateral facial clefts makes it most difficult to assess
      surgical success, particularly in terms of long-term outcome. The aim of this
      work was to examine the rationale for the current protocol used for cleft surgery
      at the Grenoble University Hospital. In a first group of 28 children, a 3-step
      surgical protocol was applied. The first two steps were performed between 4 and 8
      months with at least 3 months between each procedure. Skoog's unilateral cheilo
      rhino-uranoplasty was used, associated with a periosteal tibial graft. The third
      step, performed between 10 and 12 months, was for staphylorraphy. Outcome was
      analyzed at 15 years and evidenced the deleterious effect of excessive and
      asymmetrical premaxillary scars, of the 2-step cheiloplasty and of columella
      lengthenings from the lip. The frequency of secondary revision of the superior
      labial vestibule and the medial labial tubercule (43%) was considered to be high;
      this procedure should be re-examined as should be osteotomy (32% revision).
      Palatine closure, acquired in 82% of the cases and premaxillary stability,
      achieved in 86%, would appear to favor use of the periosteal tibial graft. The
      osteogenic capacity of this graft tissue was less satisfactory after a second
      harvesting (from the same tibia three months later). These results have led us to
      modify our protocol, favoring early and total closure of the bony palate and
      continued use of the periosteal tibial graft. We now use the following operative
      protocol: premaxillary alignment using an active orthopedic plate at 2 months,
      lip adhesion associated with staphylorraphy and passive palatine contention plate
      at 3 months, definitive bilateral cheilo-uranoplasty associated with a single
      periosteal graft at 7 months. The preliminary results with this protocol in a
      group of 12 children have shown better quality scars, more harmonious maxillary
      arches, an excellent occlusion of the deciduous dentition, and preservation of
      the positive results obtained with the periosteal tibial graft.

PMID- 11577473
TI  - [Orthopedic treatment of labio-maxillo-palatal clefts: our approach].
AB  - Many authors use a preliminary orthopedic procedure before cleft lip and palate
      surgical closure in order to prevent possible bone distortion following the
      rupture of the muscle belts resulting from the cleft. Actually, this is generally
      not only an orthopedic treatment but rather a surgical orthopedic step which
      includes lip adhesion before the surgical closure of the clefts. Following the
      procedures proposed by Georgiade and Latham, we have used since 1996 a treatment
      based on traction applied with an elastic chain on splints attached by
      transmaxillary pins for certain types of clefts, namely unilateral complete
      clefts with endognathy of the small fragment, unilateral complete clefts larger
      than 7 mm, bilateral wide complete clefts with premaxilla protrusion, and
      bilateral wide complete clefts with collapsus and premaxillary protrusion.
      Technical procedures vary with the type of cleft. Standard procedures with or
      without jacks are used for the other types of complete clefts. These orthopedic
      procedures with elastic traction are performed between the 3rd and 6th week,
      before lip adhesion of the upper part of the lip (combined with release of skin
      and subcutaneous tissues from the underlying alar cartilage). A palatine plate
      with or without a jack, fitted most of the time with a spring for nostril
      support, is then inserted until surgical closure.

PMID- 11577474
TI  - [Transplantation of the tibial periosteum. Harvesting technics].

PMID- 11577475
TI  - [Gingivoplasty in labio-maxillary clefts].

PMID- 11577476
TI  - [The treatment of labio-palatal clefts. Is nothing new under the sun? Perhaps!].

PMID- 11577477
TI  - Cancer statistics 2001: quo vadis or whither goest thou?
AB  - In his first Guest Editorial for CA as newly elected President of the American
      Cancer Society, Dr. Dileep Bal moves beyond the encouraging trends reported in
      the annual cancer statistics article to target areas for future efforts and
      improvement. Noting that resources and the public health activities of local,
      regional, and national medical communities should focus on cancer prevention,
      screening and early detection/treatment, technology transfer, and research, Dr.
      Bal emphasizes the feasibility of the 2015 goals set by the ACS: A 25% reduction
      in cancer incidence and a 50% reduction in mortality from cancer.

PMID- 11577478
TI  - Cancer statistics, 2001.
AB  - Each year the American Cancer Society compiles estimates of the number of new
      cancer cases and deaths expected in the US in the current year and the most
      recent data on cancer incidence, mortality, and survival. An estimated 1,268,000
      new cases of cancer will be diagnosed in the year 2001 and an estimated 553,400
      Americans will die from cancer. Overall cancer incidence and death rates have
      continued to decrease in men and women since the early 1990s, and the decline in
      overall cancer mortality has been greater in recent years. Despite reductions in
      age-adjusted rates of cancer death, the total number of recorded cancer deaths in
      the US continues to increase, due to an aging and expanding population. Large
      disparities in cancer incidence and mortality across racial/ethnic groups
      continue. Black men and women experience higher incidence of cancer and poorer
      survival than white men and women. The disparity in survival reflects both
      diagnosis of cancer at later disease stages, and poorer survival within each
      stage of diagnosis.

PMID- 11577479
TI  - American Cancer Society guidelines for the early detection of cancer: update of
      early detection guidelines for prostate, colorectal, and endometrial cancers.
      Also: update 2001--testing for early lung cancer detection.
AB  - Updates to the American Cancer Society (ACS) guidelines regarding screening for
      the early detection of prostate, colorectal, and endometrial cancers, based on
      the recommendations of recent ACS workshops, are presented. Additionally, the
      authors review the "cancer-related check-up," clinical encounters that provide
      case-finding and health counseling opportunities. Finally, the ACS is issuing an
      updated narrative related to testing for early lung cancer detection for
      clinicians and individuals at high risk of lung cancer in light of emerging data
      on new imaging technologies. Although it is likely that current screening
      protocols will be supplanted in the future by newer, more effective technologies,
      the establishment of an organized and systematic approach to early cancer
      detection would lead to greater utilization of existing technology and greater
      progress in cancer control.

PMID- 11577480
TI  - Childhood cancer: patterns of protocol participation in a national survey.
AB  - Cancer is still the chief cause of death by disease in children, ages one to 14.
      As improved survival rates have been reported for pediatric cancer patients who
      are treated on controlled clinical trials, it is important to understand the
      national utilization of such protocols. In 1993, a survey of childhood cancer was
      conducted by the Commission on Cancer of the American College of Surgeons. Data
      regarding type of disease, protocol participation, age, sex, race, insurance, and
      geographical region were voluntarily submitted by more than 200 hospital cancer
      registries. Included in this study were 2,208 children and adolescents 21 years
      of age or younger who were diagnosed in 1987, and 2,293 who were diagnosed in
      1992. Pediatric centers (i.e., members of the Pediatric Oncology Group or
      Children's Cancer Group) submitted 55.1% of the cases and other institutions,
      44.9%. It was found that more patients treated at pediatric centers were on
      protocols (53.8%) than were those treated at other institutions (25.1%). In
      general, the younger the patient (five years of age or younger), the greater the
      chance of being on protocol (pediatric centers, 63.7%; others, 42.0%), with very
      poor adolescent protocol participation (pediatric centers, 34.8%; others, 12.1%).
      Nevertheless, overall protocol participation was still lower than expected, even
      in children younger than five years of age, and adolescent participation in
      controlled clinical trials was low and similar to adult figures. The percentage
      of childhood cancer cases seen at pediatric centers was smaller than in other
      series. It was concluded that pediatric cancer centers need to continue to
      encourage patient participation in controlled clinical trials, with special
      emphasis on adolescents.

PMID- 11577481
TI  - Alternative therapies for curing cancer: what do patients want? What do patients
      need?
AB  - Despite her scientific training and experience in medical practice, after being
      diagnosed with an indolent non-Hodgkin's lymphoma, the author was subjected to
      intense pressure about alternative therapies from well-meaning friends and
      relatives. While insulated at first from these forces, disease recurrences and
      progression increased her vulnerability to the lure of seemingly gentler
      approaches. A data-driven study of alternative therapeutic methods, however,
      convinced the author that investigational strategies offered her a better chance
      of cure or improvement than unproven alternative methods. She offers guidelines
      for physicians about what patients want, and emphasizes the importance of hope,
      caring, and information.

PMID- 11577483
TI  - Despite ban, actors continue to light up on screen.

PMID- 11577482
TI  - Cellular phones and risk of brain tumors.
AB  - As cellular telephones are a relatively new technology, we do not yet have long
      term follow-up on their possible biological effects. However, the lack of
      ionizing radiation and the low energy level emitted from cell phones and absorbed
      by human tissues make it unlikely that these devices cause cancer. Moreover,
      several well-designed epidemiologic studies find no consistent association
      between cell phone use and brain cancer. It is impossible to prove that any
      product or exposure is absolutely safe, especially in the absence of very long
      term follow-up. Accordingly, the following summary from the Food and Drug
      Administration Center for Devices and Radiological Health offers advice to people
      concerned about their risk: If there is a risk from these products--and at this
      point we do not know that there is--it is probably very small. But if people are
      concerned about avoiding even potential risks, there are simple steps they can
      take to do so. People who must conduct extended conversations in their cars every
      day could switch to a type of mobile phone that places more distance between
      their bodies and the source of the RF, since the exposure level drops off
      dramatically with distance. For example, they could switch to: a mobile phone in
      which the antenna is located outside the vehicle, a hand-held phone with a built
      in antenna connected to a different antenna mounted on the outside of the car or
      built into a separate package, or a headset with a remote antenna to a mobile
      phone carried at the waist. Again the scientific data do not demonstrate that
      mobile phones are harmful. But if people are concerned about the radiofrequency
      energy from these products, taking the simple precautions outlined above can
      reduce any possible risk. In addition, people who are concerned might choose
      digital rather than analog telephones, since the former use lower RF levels.

PMID- 11577484
TI  - American Cancer Society guidelines for the early detection of cancer.

PMID- 11577485
TI  - Cervical cancer: successes and failures.
AB  - The decline in deaths from cervical cancer in the US, as well as the improved
      survival of women with advanced disease have resulted, according to Dr. Rubin,
      from widespread application of routine screening with the Pap test, the emergence
      of gynecologic oncology as a distinct medical subspecialty, and the completion of
      important clinical trials.

PMID- 11577486
TI  - Cervical cancer: prevention, diagnosis, and therapeutics.
AB  - Cervical cancer is a leading cause of cancer deaths in women worldwide. Because
      of its association with human papilloma virus infection, as well as the ability
      to screen for premalignant stages of the disease, it is now largely a preventable
      disease. This article describes the molecular basis for cervical cancer, and
      presents a clinical overview of current treatment approaches and technological
      advances, emphasizing the unique aspects of this viral disease as it relates to
      the immune system and vaccination or other immunotherapeutic strategies.

PMID- 11577487
TI  - Communicating with patients about quality of life issues.

PMID- 11577488
TI  - Family support in advanced cancer.
AB  - Changes in the health care system have resulted in a shift of cancer care from
      the in-patient arena to ambulatory and home settings. This shift has likewise
      translated into increased family involvement in the day-to-day care of the person
      with cancer. Cancer patients have multifaceted needs, including disease and
      treatment monitoring, symptom management, medication administration, emotional
      support, assistance with personal care, and assistance with instrument care.
      Family caregivers may be ill prepared to assume these tasks, requiring
      information on the disease and treatment, as well as instruction in technical and
      care skills. Moreover, caregiving must be balanced against already established
      roles and role responsibilities. In addition, family caregivers have their own
      emotional responses to the patients' diagnosis and prognosis, and may require
      coaching and emotional support themselves. The health care system can facilitate
      positive outcomes by embracing the family caregiver as a partner in the health
      care team, providing instruction and guidance to the caregiver as he/she assumes
      this role, and evaluating the home care situation. Research to date has only
      scratched the surface of testing interventions that meet the needs of the cancer
      caregiver. A research agenda is proposed to more fully elucidate the cancer
      caregiver's experience throughout the illness and treatment trajectory, and
      identify the means to effecting positive outcomes for the person with cancer,
      their family caregiver, and the health care system.

PMID- 11577489
TI  - Nausea, vomiting, and retching: complex problems in palliative care.
AB  - Patients with advanced cancer commonly experience nausea, vomiting, and/or
      retching (NVR) as a result of the malignant process and its treatment. Recently,
      increasing attention is being focused on end-of-life care, which includes relief
      or reduction of symptoms such as NVR. Pre-chemotherapy preparation and patient
      education in the palliative care setting are essential to preventing acute and
      delayed distress from NVR, as well as anticipatory symptoms. Careful assessment
      of chemotherapy-related symptoms should distinguish between the three phenomena
      rather than taking a global approach. Strategies for preventing anticipatory
      nausea, for instance, may differ significantly from those designed to reduce
      frequency of vomiting. Management of anticancer treatment-related NVR should
      incorporate both pharmacologic and nonpharmacologic approaches, whenever
      appropriate, with the overall goal of improving and/or maintaining the patient's
      quality of life.

PMID- 11577490
TI  - Arsenic.
AB  - The toxicity and carcinogenicity of arsenic are well known, but vexing questions
      remain. The current controversy over the appropriate Federal limit for arsenic in
      drinking water highlights some of the difficult scientific, ethical, economic,
      and political issues that complicate standard-setting in occupational and
      environmental health. These include limitations in the scientific evidence
      concerning the risk at low doses, uncertainty about the appropriate mathematical
      models for estimating the risk at low-level exposures based on data from higher
      level exposures, and controversies concerning the appropriate safety margin,
      level of evidence required for standard-setting, and costs of remediation.

PMID- 11577491
TI  - Multiple myeloma: what's new.
AB  - With conventional therapy, only 5% of multiple myeloma patients achieve complete
      response. But in recent clinical trials of high-dose therapy with autologous
      hematopoietic stem cell transplant, complete remission rates of 25-30% can be
      affected with median survival exceeding 5 years. Newer approaches in clinical
      trials, including more potent induction regimens utilizing thalidomide, alone or
      in combination with dexamethasone, are improving treatment outcomes. The authors
      suggest that potential for a cure now appears to be within reach.

PMID- 11577492
TI  - Multiple myeloma: an old disease with new hope for the future.
AB  - Multiple myeloma is a currently incurable malignancy of terminally differentiated
      plasma cells. It typically occurs in older patients (median age 71 years).
      Clinical manifestations result from monoclonal protein (immunoglobulin)
      production and its accumulation in the serum and/or urine, anemia, lytic bone
      disease, hypercalcemia, renal insufficiency, and immune deficiency. Myeloma cells
      have low proliferative activity--most myeloma experts opine that the initial
      oncogenic event occurs 10-15 years before clinical disease manifestation. In
      addition, myeloma cells develop multiple chromosomal abnormalities, which may
      explain the native resistance of myeloma patients to conventional therapy and our
      inability to completely eradicate the disease. Indeed, with conventional therapy,
      only 5% of patients achieve complete response. Minimal improvement has been
      observed with conventional therapies over the past 20-30 years; the median
      duration of initial response remains approximately 18 months with median survival
      in the 36-month range. However, recent clinical trials have established high-dose
      therapy with autologous hematopoietic stem cell transplant as superior to
      conventional therapy: complete remission rates of 25-30% can be affected with
      median survival exceeding 5 years. Newer approaches to improve treatment outcomes
      are in active clinical trials including: more potent induction regimens utilizing
      thalidomide, alone or in combination with dexamethasone; tandem transplants to
      improve complete remission rates; newer approaches to maintenance therapy using
      thalidomide with corticosteroids; non-myeloablative therapy with allogeneic
      transplant; and post-transplant vaccinations.

PMID- 11577493
TI  - Oral mucositis complicating chemotherapy and/or radiotherapy: options for
      prevention and treatment.
AB  - Chemotherapy- and radiotherapy-induced oral mucositis represents a therapeutic
      challenge frequently encountered in cancer patients. This side effect causes
      significant morbidity and may delay the treatment plan, as well as increase
      therapeutic expenses. The pathogenesis of this debilitating side effect can be
      attributed to the direct mucosal toxicity of cytotoxic agents and ionizing
      radiation and to indirect mucosal damage caused by a concomitant inflammatory
      reaction exacerbated in the presence of neutropenia, and the emergence of
      bacterial, mycotic, and viral infections. The prophylactic and therapeutic
      armamentarium for the treatment of oral mucositis consists of locally and
      systemically applied nonpharmacological measures and pharmacotherapeutics.

PMID- 11577494
TI  - Nutritional advice for cancer survivors.
AB  - A diagnosis of cancer is often accompanied by feelings of loss of control.
      Focusing on nutrition and healthful choices about foods, supplements, and
      activity, Dr. Eyre suggests, helps survivors actively plan and participate in
      self-care strategies.

PMID- 11577495
TI  - Nutrition during and after cancer treatment: a guide for informed choices by
      cancer survivors.
AB  - Many studies have been conducted about dietary interventions aimed at preventing
      cancer. The American Cancer Society has published guidelines on diet, nutrition
      and cancer prevention, which are updated periodically as new evidence emerges,
      and other groups, too, have issued statements or guidelines about nutritional
      strategies to prevent cancer. Much less is known, however, about optimal
      nutrition for cancer survivors. This report looks at the different phases of
      cancer survivorship, from active treatment to advanced disease, and presents
      existing evidence from which informed decisions can be made regarding dietary
      choices. Popular complementary and alternative methods related to dietary
      intervention are reviewed. Nutrition information is also provided according to
      common cancer sites. As this is an area that requires survivors and health care
      providers to communicate effectively, a special section on "frequently asked
      questions" is provided for use as a patient education handout.

PMID- 11577496
TI  - Diesel exhaust.

PMID- 11577498
TI  - Epidemics of meningococcal disease. African meningitis belt, 2001.

PMID- 11577499
TI  - CRGs: a new risk adjustment tool for capitation management.

PMID- 11577497
TI  - PC-SPES: current evidence and remaining questions.

PMID- 11577500
TI  - In role reversal, more provider groups demand concessions from plans.
AB  - Because of their recognizable brand name and position in their communities, some
      provider groups are placing demands on health plans--and getting what they want.
      Here's a look at several places where it's happening, what makes it work, and
      what happens when plans try to push back.

PMID- 11577501
TI  - Risk-based capital requirements may be a boon to capitation.
AB  - Don't count capitation out yet. Especially not when state-imposed risk based
      capital requirements make it attractive. See how the numbers play out.

PMID- 11577502
TI  - WellPoint taking new approach to controlling 'vampire drugs'.
AB  - Are pharmaceutical costs sucking too much money out of the system? A California
      health plan is getting ready to introduce the newest thing in drug cost controls-
      reference pricing. They'll tell what they'll pay for, and stop talking about what
      they won't pay for.

PMID- 11577503
TI  - California Blue Cross redirects incentive dollars from UM to quality.
AB  - In its realignment of physician incentives, a California plan has taken money
      away from the utilization management bonus pool and put it into quality. Here are
      the details.

PMID- 11577504
TI  - Competition will encourage doctors to provide service in defined contribution.

PMID- 11577505
TI  - EMTALA questions and answers.

PMID- 11577506
TI  - Warning: are you prepared to lose your ED after a natural disaster?
AB  - Natural catastrophes that can lead to loss of the ED itself are often overlooked
      in disaster plans and drills. Plans should address evacuation of patients,
      including transportation and equipment to take, and drills should include these
      scenarios. You should have alternatives to cope with loss of power and
      communications, such as oxygen-powered backup generators. To prepare for a deluge
      of individuals coming to the ED after a disaster, decide how to utilize
      volunteers, and limit access by using disaster identification vests. New
      Environment of Care standards from the Joint Commission on Accreditation of
      Healthcare Organizations require you to perform a hazard and vulnerability
      analysis.

PMID- 11577507
TI  - Boost quality of care: track medication use.
AB  - A medication use study conducted by 10 EDs resulted in reduced costs and more
      consistent care. Tracking medication usage can gauge whether clinicians are
      succeeding at resolving symptoms in the ED. The study's findings included
      increased use of pain medicines, antibiotics, breathing treatments,
      gastrointestinal medicines, and anti-inflammatories. You can measure the use of
      expensive medications vs. less costly alternatives.

PMID- 11577508
TI  - ED makes nurses happy by outsourcing calls.
AB  - Outsourcing of patient calls can save significant time, increase satisfaction
      among patients and nursing staff, and reduce unnecessary ED visits. The program
      provides 24-hour triage for patient calls, at a cost of approximately $80,000 a
      year. Each forwarded call saves ED nurses about five or 10 minutes. Patient calls
      are a liability risk for the hospital because of inconsistent information and
      inadequate documentation.

PMID- 11577509
TI  - Victory: you'll be paid for ED observation.

PMID- 11577510
TI  - Model for care of chronically ill blends DM and CM approaches.

PMID- 11577511
TI  - CAD initiative begins at the hospital with medication, lifestyle interventions.
AB  - Re-think the conventional wisdom about when to start cardiac rehab therapies.
      Researchers at the University of California Los Angeles are beginning right after
      heart surgery with education and medication regimens that used to wait until a
      patient returned to home.

PMID- 11577512
TI  - Involve nurses and patients to change physician behavior.
AB  - Even the best physician-directed initiative to boost use of beta blockers, ACE
      inhibitors, and other proven strategies might not be enough to change behavior.
      When University of Michigan clinicians added nurses and patients to the team,
      compliance with these effective strategies soared.

PMID- 11577513
TI  - Feds announce management guidelines to address troubling growth of COPD.
AB  - New guidelines from the federal government point out how to address the fourth
      leading cause of death in the United States.

PMID- 11577514
TI  - Helical CT challenges model for diagnosing pulmonary embolism.
AB  - But, some experts say, it's too soon to rely on this new technology exclusively.
      The best practice for diagnosing PE, according to some hospitalists: an
      integrated approach using pretest probability models, V/Q scanning, helical CT,
      and noninvasive lower extremity testing.

PMID- 11577515
TI  - [Urinary incontinence].

PMID- 11577516
TI  - [Tossing for a clone?].

PMID- 11577517
TI  - [Female pelvic floor].

PMID- 11577518
TI  - [Neurogenic bladder disturbances].
AB  - Knowledge of the neurophysiology of bladder control is growing, as better
      diagnostic methods are developed and because clinical interest in the field is
      greater and treatments are better. It is problematic that the symptoms are very
      few and do not provide much information about the lesions in the nervous system.
      We describe the bladder symptoms in most neurological diseases, and the
      neurophysiology of normal voiding is described. A strategy for handling
      neurological bladder symptoms is outlined.

PMID- 11577519
TI  - [Urologic treatment and control of persons with spinal cord injuries].

PMID- 11577520
TI  - [Is it possible to optimize the use of economical and professional resources in
      the diagnosis and treatment of urinary incontinence?].
AB  - In 1996, the estimated costs in Sweden, owing to urinary incontinence, increased
      to $0.5 billion or 2-3% of the health budget. In Denmark, the cost of urinary
      incontinence is unknown, but probably much the same as that in Sweden. Growth of
      the elderly population, a rise in the costs of routine incontinence care (mostly
      pads), and an increasing ability to cure incontinence challenge the existing
      economic priorities. Economic analysis in this field is sparse. Treatment of
      urinary incontinence imposes a significant financial burden on society. Based on
      a review of the literature, the authors recommend increased focus on health
      economy and preventive possibilities, as well as a change in the diagnostic and
      treatment algorithm of urinary incontinence.

PMID- 11577522
TI  - [Urinary incontinence. Status and current problems].

PMID- 11577521
TI  - ["Tension-free vaginal tape--TVT. Another new surgical procedure for female
      stress incontinence].

PMID- 11577523
TI  - [Lower urinary tract symptoms in fertile women after pregnancy and labor].

PMID- 11577524
TI  - [General practitioners' knowledge of and attitude to assessment and treatment of
      women with urinary incontinence. A questionnaire among general practitioners in
      Denmark].
AB  - INTRODUCTION: Urinary incontinence is a common problem for adult women, and the
      need for assessment and treatment of incontinence is expected to increase in the
      future. The aim of this study was to elucidate the general practitioners' (GPs)
      knowledge about and attitude to women with urinary incontinence. METHODS: A
      questionnaire was posted to 1700 randomly selected GPs in 1998 and 1999. RESULTS:
      A total of 1071 (63%) GPs responded at least once. Five hundred (29%) returned
      the questionnaire both years. About 50% expressed a positive interest in the
      management of urinary incontinence. Only 24% felt that their knowledge was
      sufficient to manage incontinence. About 50% and 66% of the GPs would probably
      refer a patient with stress incontinence or urge incontinence to a specialist.
      The GPs' proposals for assessment and treatment were mainly consistent with good
      clinical practice. There were only minor changes in knowledge and attitude from
      1998 to 1999. DISCUSSION: GPs' interest in urinary incontinence is moderate and
      management is characterised by a high referral rate to a specialist. Most GPs.
      consider their knowledge to be inadequate. There is need for education to ensure
      sufficient knowledge and to change the attitude, so that first-line assessment
      and treatment of urinary incontinence is carried out in general practice.

PMID- 11577525
TI  - [What are the direct costs of an abdominal aortic aneurysm repair in a Danish
      hospital?].
AB  - INTRODUCTION: The aim of the study was to estimate the direct cost of an
      abdominal aortic aneurysm (AAA) repair and to validate it against the national
      Diagnostic Related Group (DRG) costs. MATERIAL: Over a three-year period, between
      January 1996 and December 1998, a total of 100 men were selected at random from a
      series of 197 patients treated with open surgery for (AAA) at the Department of
      Vascular Surgery, Viborg Hospital. RESULTS: The total cost of an AAA operation
      without complications was estimated to be 70,000 DKK, compared to the DRG price
      of 79,000 DKK. Complications were significantly more frequent after emergency
      repair (odds ratio = 4.3 (95% CI; 1.9-10.1)). A statistically significant
      difference was seen in the cost of AAA repair between elective and emergency
      operations with rupture (p < 0.05), mainly because of the longer stay in
      hospital. DISCUSSION: The estimated cost is sufficiently reliable to be used in
      analysis of cost-effectiveness.

PMID- 11577526
TI  - [Tobacco and alcohol are risk factors of complicated peptic ulcers. A prospective
      cohort study].
AB  - Both the incidence of and mortality from bleeding and perforated peptic ulcers
      are growing. We assessed the association between smoking, ingestion of alcohol
      (including the type of alcoholic beverage), and risk of a complicated peptic
      ulcer in a population-based study of 26,518 Danish subjects followed up for an
      average of 13.4 years. There were 214 cases of incident bleeding and 107 cases
      with perforated ulcers. We estimated the relative risks (RRs) of incident
      bleeding and perforated peptic ulcers with the Poisson regression analysis.
      Smoking more than 15 cigarettes a day compared with never smoking increased the
      risk of a perforated ulcer more than threefold (RR = 3.5; 95% confidence interval
      [CI] = 1.7-7.1). Ingestion of more than 42 drinks a week increased the risk of a
      bleeding ulcer fourfold (RR = 4.4; 95% CI = 2.3-8.3) compared with ingestion of
      less than one drink a week. Comparison of the same group, showed that subjects
      who ingested more than 21 drinks a week, but no wine, were at a higher risk of a
      bleeding ulcer (RR = 8.8; 95% CI = 2.2-35) than drinkers of the same amount of
      alcohol, but with more than 25% of their intake as wine (RR = 2.4; 95% CI = 1.0
      6.0).

PMID- 11577527
TI  - [Receptor mapping in living human beings by means of positron emission
      tomography].
AB  - PET can map neurotransmitter synthesis, storage, release, binding to receptors,
      and re-uptake in the brain with tracer concentrations in the picomolar or
      nanomolar range. Tracers are analogues of naturally occurring precursors or
      ligands, or are drugs, which bind with varying degrees of specificity to receptor
      subtypes in the brain. Tracers have been synthesised for many transmitter
      systems, but dopaminergic and serotonergic neurotransmissions are the main foci
      of current efforts to selectively trace synthesis, storage, re-uptake, or post
      synaptic binding of neurotransmitters. Common measures of the tracer uptake and
      binding include precursor clearance (k3), a measure of transmitter synthesis and
      trapping, and binding potential (pB), a measure of the receptor binding per unit
      of unbound tracer, and hence a measure of the release of the endogenous
      transmitter, or the occupancy of a drug. Dopamine tracers are used in diseases of
      the basal ganglia, whereas serotonin, benzodiazepine, and opiate tracers are used
      in lesions of the cerebral cortex. PET has revealed loss of dopaminergic
      terminals and dopamine synthetic capacity in Parkinson's disease, MPTP
      intoxication, and Lesch-Nyhan's syndrome; release of dopamine after
      administration of cocaine and amphetamine, and in motor activity and cognition;
      increased synaptic dopamine and release of dopamine, and the 70-90% neuroleptic
      occupancy of dopamine receptors in the striatum, in patients with schizophrenia;
      loss of muscarinic and nicotinergic receptors in Alzheimer's disease, and
      benzodiazepine and opiate receptors in stroke, epilepsy, and Huntington's chorea;
      altered opiate receptors in chronic pain and drug abuse; and release of opiates
      in analgesia; but changes in serotonin synthesis, transport, and binding in
      affective or psychotic disorders remain elusive.

PMID- 11577528
TI  - [The significance of reproductive history for prognosis of primary breast
      cancer].
AB  - The aetiological impact of a woman's reproductive history on breast cancer is
      well established, whereas the prognostic influence of the reproductive pattern is
      less well described. A literature search with focus on three Danish studies is
      described. Status as parous/nulliparous and number of births appear to have no
      prognostic influence. Women who have their first child at an early age have a
      lower survival than women who have postponed their first childbirth. This may
      eventually be explained by selection, i.e. that women with an early first full
      term pregnancy represent a group with a more malignant disease. Women diagnosed
      in the first two years after childbirth have a significantly lower survival,
      probably because the cancer, being subclinical during pregnancy, is affected by
      the high oestrogen concentrations with aggressive growth as the outcome.
      Pregnancy after treatment of breast cancer does not appear to have a negative
      influence on the prognosis.

PMID- 11577530
TI  - [Pulmonary artery catheter monitoring does not reduce morbidity and or mortality
      in major surgery].

PMID- 11577529
TI  - [Acute deep venous thrombosis and PET scanning with 2-fluoro-2-deoxy-D-glucose,
      FDG].
AB  - A 30-year-old woman with a history of malignant non-Hodgkin lymphoma with a bulky
      tumour on the right thigh, primarily treated with high-dose chemotherapy and
      involving field radiation, developed a deep venous thrombosis (DVT) in her right
      leg two weeks after the end of therapy. Positron emission tomography with
      fluorine-18 flourodeoxyglucose (FDG PET) was performed to assess the response of
      the lymphoma to therapy. The PET scan showed several sites of pathological, high
      tracer uptake corresponding to residual lymphoma, but also intense activity in
      the right calf correlating to the deep veins located peripheral to the site of
      DVT. FDG PET performed two months later showed no pathological FDG uptake in this
      area. CONCLUSION: Acute DVT may cause pathological uptake of FDG and should
      therefore be considered a possible pitfall in the interpretation of FDG PET.

PMID- 11577531
TI  - Treating attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is a chronic childhood disorder
      characterized by inattention, distractibility, impulsivity, and restlessness.
      ADHD symptoms impair the child's ability to function at home, in school, and in
      the community. When ADHD is untreated, the child is at increased risk for school
      failure, substance abuse, and psychiatric disorders. New clinical practice
      guidelines from the American Academy of Pediatrics specify diagnosis and
      treatment for childhood ADHD, including psychosocial interventions,
      psychopharmacology, educational modifications, skill training, and social
      support.

PMID- 11577532
TI  - Finding and evaluating clinical practice guidelines.
AB  - Clinical practice guidelines are valuable, clinical decision-making aids for
      preventive, diagnostic, therapeutic, and palliative patient care. This article
      identifies ways to access clinical practice guidelines and discusses evaluative
      criteria for identifying gold-standard evidence-based practice guidelines.
      Finally, clinicians are reminded of crucial questions to ask before applying any
      guidelines to patient care.

PMID- 11577533
TI  - When to suspect squamous cancer at colposcopy.
AB  - Advanced practice nurses are increasingly using colposcopy to investigate
      abnormal cervical cytology. Specific colposcopic features can lead the clinician
      to suspect squamous cancer. This article discusses vascular pattern study,
      examination evaluation, lesion grading, and correlating colposcopy with histology
      and cytology to aid in identifying squamous cancer.

PMID- 11577534
TI  - Learning from (family) history.

PMID- 11577535
TI  - Guide to care for patients. Hypertension.

PMID- 11577536
TI  - The physiology of primary care provider legislation, Part 2.

PMID- 11577537
TI  - Leukocyte-blood vessel interactions.

PMID- 11577538
TI  - Extracellular matrix.

PMID- 11577539
TI  - The regulation of IgE synthesis.

PMID- 11577540
TI  - Effector roles of IgE antibodies: targeting allergen to the high-affinity IgE
      receptor for Fc epsilon RI-dependent signaling and antigen presentation.

PMID- 11577542
TI  - Cytokines in allergic inflammation.

PMID- 11577541
TI  - Lipid inflammatory mediators: leukotrienes, prostaglandins, platelet-activating
      factor.
AB  - The lipid mediators, leukotrienes, prostaglandins, and PAF play an important role
      in the complex inflammatory process of airway eosinophilia, edema hypersecretion
      of mucus, and AHR observed in patients with asthma. These mediators are also
      likely key participants in the pathogenesis of other allergic diseases. An
      important goal of future research is to clarify the complex interactions between
      the lipid mediators and the inflammatory stimuli that regulate their production.
      Novel inhibitors and antagonists of the lipid mediators, such as the CysLT1
      receptor antagonists, have recently been developed that have great promise in the
      treatment of allergic diseases.

PMID- 11577543
TI  - Mechanisms of allergic rhinitis.

PMID- 11577544
TI  - Nasal polyps and sinusitis.

PMID- 11577545
TI  - Mast cells and basophils.

PMID- 11577546
TI  - Allergic eye disorders.

PMID- 11577547
TI  - Asthma.
AB  - Inflammation plays an integral role in the pathophysiology of asthma. With
      advances in molecular biological techniques and newer animal models, our insight
      into this process is advancing rapidly. A greater understanding of the
      interactions of the various elements of the inflammatory response and their
      interactions is thus evolving. This progress in our knowledge and understanding
      of the disease process appears to raise even more questions, but such is the
      nature of research. It is also known that no single abnormality of cells or
      mediators will suffice to explain the pathogenesis of asthma. Enhanced knowledge
      of molecular and cellular events in the inflammatory process would inevitably
      lead to newer, more specific, therapeutic agents, which would potentially be
      curative rather than palliative.

PMID- 11577548
TI  - Atopic dermatitis.

PMID- 11577549
TI  - Urticaria.

PMID- 11577550
TI  - Anaphylaxis and inflammation.

PMID- 11577551
TI  - Nonanaphylactic drug disorders.

PMID- 11577552
TI  - Eosinophils.

PMID- 11577553
TI  - Vasculitis.
AB  - Progress has been made in the classification, characterization, and
      identification of vasculitis; a heterogeneous disease with various vessel sizes
      and types of involvement. Understanding pathogenetic mechanisms and the kinetics
      of the inflammatory-immune response is still in its infancy. With the
      availability of new tools for diagnosis and the use of molecular biological
      techniques at the cellular, tissue, and fluid phase levels will open the doors
      for new understanding of the etiology and mechanism(s) of this group of diseases.

PMID- 11577554
TI  - Allergic bronchopulmonary aspergillosis, allergic fungal sinusitis, and
      hypersensitivity pneumonitis.

PMID- 11577555
TI  - Pharmacological approaches.
AB  - Treatment of moderate to severe atopic disease may require multidrug regimens,
      reflecting the multifaceted nature of allergic inflammation. Furthermore, despite
      the central role of Th2 inflammation in allergic rhinitis (15), asthma (14), and
      atopic dermatitis (11), specific mediator antagonists may not be uniformly
      successful in the treatment of all atopic disorders. For example, antihistamines
      are very effective treatment for the symptoms of allergic rhinitis (41), but have
      minimal benefit in the treatment of asthma (42-44). Current research efforts are
      ongoing to identify and develop therapies aimed at critical junctures in the
      immunopathological process. For example, animal studies have suggested that IL-4
      and IL-13 are two cytokines that are pivotal in the generation of airway allergic
      inflammation. Blocking the action of these cytokines may markedly decrease the
      allergic inflammation (17,125).

PMID- 11577556
TI  - Synthetic and genetically engineered allergen derivatives for specific
      immunotherapy of type I allergy.

PMID- 11577557
TI  - Anti-IgE antibody therapy.
AB  - From the published studies of E25, it is now clear that this approach to treating
      atopic disease can be successful. But there remain many issues, both practical
      and biological. For the study of atopic disease, a potentially excellent new tool
      has been provided that could allow IgE to be effectively eliminated, given the
      correct-dosing regimen, and provide the investigator with a means to ask
      questions about the role of IgE in the expression of a particular disease. No
      place is this more evident than in the study of asthma for which a long-standing
      debate revolves around the precise contribution of atopy to the genesis and
      maintenance of this disease. Furthermore, use of the drug may finally resolve
      questions about the role of IgE in parasitic rejection. From the perspective of
      the patient, at a minimum, the drug provides a proof-of-concept for all potential
      therapies seeking to reduce circulating IgE levels. With proper consideration of
      dosing, the drug appears as if it could provide remarkable improvement in the
      course of atopic disease. Some concerns still revolve around the improvement
      roles IgE may play in parasitic diseases, the cost of therapy, and that very long
      term treatment effects have yet to be studied.

PMID- 11577558
TI  - Allergen injection immunotherapy.

PMID- 11577559
TI  - DNA immunomodulation of asthma.
AB  - This is an exciting time in the chronology of asthma and allergic diseases.
      Although the pharmacopeia for treatment of these diseases has advanced greatly,
      most of our current therapies are aimed at the symptoms, rather than the
      underlying mechanism. Immunotherapy remains the only therapeutic modality that
      addresses the underlying mechanism, albeit by effects are still not fully
      understood. The approaches summarized in this chapter, alone or in combination,
      may yet allow one to reverse the atopic state. Meanwhile, other innovative DNA
      based approaches are being developed, including the use of allergen DNA with or
      without CpG. Because most of the Th2 cytokines are on chromosome 5, the
      completion of the human genome project may open whole new venues of research
      aimed at controlling these cytokines at the chromosomal level.

PMID- 11577560
TI  - Neutrophils.

PMID- 11577561
TI  - Lymphocytes.

PMID- 11577562
TI  - [Experimental model of infection of Helicobacter pylori in the mouse. A study of
      gastric damage caused by indomethacin].
AB  - INTRODUCTION: The action of non-steroidal anti-inflammatory drugs (NSAIDs) on the
      Helicobacter Pylori (Hp) infected mucosa is a matter of debate. Some authors
      consider them to cause additive iatrogeny whilst others attribute a purportedly
      protective action to them. The development of on experimental animal model could
      help clarify this phenomenon. OBJECTIVES: 1--To develop an animal model of Hp
      gastric infection. 2--To evaluate the aggressiveness of NSAIDs in this model.
      MATERIALS AND METHODS: Male 6 month old BALC/C mice weighing 38 g were studied.
      Pylori Hp infection was ruled out. On three occasions, in the same week, 18 mice
      were inoculated intra-gastrically with 0.6 ml of Hp culture broth (brain-heart
      infusion) containing 1 x 10 8-1 x 10 9 CFU/ml. Another group of mice were
      inoculated with sterile saline. After two months the mice were killed and their
      stomachs studied. They were divided into groups: a) 6 Hp negative control mice.
      b) 8 Hp negative mice with prior intra-peritoneal injection of 25 mg/Kg
      indomethacin (24 hs.) c) 8 mice inoculated with Hp with indomethacin. d) 8 mice
      inoculated with Hp, without indomethacin. The stomachs were opened along the
      greater curvature and photographed macroscopically in order to map the necrotic
      area. The antrums were biopsied to test for urease and separate antrum and body
      specimens were send for staining with Warthin-Starry H & B and histopathology.
      RESULTS: All the mice inoculated with Hp acquired the infection. The necrotic
      area was larger in Group B: 55.5 +/- 7.87 mm than in Group C: 15 +/- 1.82 mm P <
      0.00019. HISTOLOGY: Group A: normal mucosa. Group B: extensive coagulation
      necrosis and focal erosions. Group C: ulcers with inflammatory infiltrate and
      smaller necrotic area, presence of Hp on the surface epithelium. Group D: no
      ulcers, Hp present. CONCLUSION: An animal model of Hp infection was successfully
      developed Hp infection could play a potentially protective role against
      indomethacin aggression in the mouse.

PMID- 11577563
TI  - Sodium-deprived rat distal colon epithelial response to acute hypoxia and
      reoxygenation.
AB  - In normal rat distal colon isolated mucosa, basal short-circuit current (Isc) is
      mostly due to chloride secretion. Isc is depressed by a brief (5 min) acute
      hypoxia and overshoots above baseline during reoxygenation. Sodium deprivation
      raises serum aldosterone levels and leads to expression of functional epithelial
      sodium channels which are amiloride-sensitive. Thus, in sodium-deprived rats
      (SDRs) Isc is dependent on electrogenic sodium absorption. Since the ion
      primarily responsible for the Isc is different in each functional condition, it
      is not known whether hypoxia and reoxygenation affect SDRs epithelial response in
      the same way as in normal rats. Therefore the electrical behavior of isolated
      mucosa preparations from normal and SDRs was studied in an Ussing chamber, and
      the effect of the epithelial sodium channel blocker, amiloride sensitive, basal
      Isc than controls. Their response to hypoxia (expressed as a fraction of basal
      Isc) was similar to controls but upon reoxygenation their recovery was
      incomplete. SDRs response to hypoxia was not affected by amiloride at any
      concentration tested. However, post-hypoxic recovery was modified by amiloride in
      a concentration-dependent way: it was incomplete at 10(-8) M, complete at 10(-6)
      M, and at 10(-4) M it overshooted above baseline values. Therefore, in sodium
      deprived rats, sodium channel blockade reverts the pattern of blunted recovery to
      the overshooting pattern seen normal rats. These results may be explained by two
      non-mutually exclusive hypotheses: Epithelial sodium channel blockade in sodium
      deprived rats might (1) unmask a basal chloride conductance, and (2) interfere
      with a negative interaction between sodium chloride conductances.

PMID- 11577564
TI  - [Granular cell tumor of the esophagus. Morphological and immunohistochemical
      study].
AB  - Granular cell tumor or Abrikosoff's tumor is an infrequent and usually benign
      neoplasm which is found predominantly in the head and neck region, especially in
      the tongue. Its esophageal location is unusual, where most of them present as
      small, well circumscribed lesions which follow a benign course. Because of its
      low incidence in this site (less than 200 cases having been reported until 1993),
      we report two cases of esophageal granular cell tumors, both of them in male
      patients. CASE 1: A 34 year old patient who presented with epigastralgia,
      heartburn and abdominal distention. He was treated endoscopically because he had
      a firm new growth in the lower third of the esophagus measuring 1 cm in diameter.
      CASE 2: A 50 year old patient who presented with digestive tract haemorrhage
      (hematemesis and melena) 5 cm above the cardias a submucosal polyp was found of
      0.8 cm in its largest diameter. MICROSCOPY: Both cases showed a subepithelially
      located new growth, composed of polygonal cells with eosinophilic granular
      cytoplasm, small rounded nuclei, and conspicuous intracytoplasmatic positivity
      for S100 protein. With these elements we reached the diagnosis of granular cell
      tumor. The bibliography is reviewed and an update is made of its histopathologic
      characteristics in addition to histogenetic and clinical considerations.

PMID- 11577565
TI  - [Role of cytokines in chronic gastritis by Helicobacter pylori].
AB  - Helicobacter pylori is a curved, gram negative bacterium that inhabits only the
      gastric mucous membrane. Since its discovery and characterization, it has been
      related to the physiopathology of gastroduodenal diseases, including gastritis,
      peptic ulcers, gastric carcinoma and MALT lymphoma. This has resulted in numerous
      hypotheses that try to explain the different events that take place during the
      inflammation. The bacterium Settler, characterized by a marked infiltration of
      inflammatory cells (neutrophils, monocytes, linfocytes, etc.) which, after being
      activated, liberate locally various chemical mediators, which cause tissue
      damage. Among these, the cytokines are important mediators in this process. We
      have revised the literature related to the various biological functions of
      cytokines in tissue damage of the gastric mucosa.

PMID- 11577567
TI  - [A new approach to the carcinogenetic process: the telomere wearing out].

PMID- 11577566
TI  - The clinical and histological spectrum of esophagitis in pediatrics. Some keys to
      its links to gastritis.
AB  - The purpose of our study was to assess the clinical and histological spectrum of
      esophagitis, seeking possible links between esophagitis and gastritis
      particularly Helicobacter pylori-associated, in pediatric patients. MATERIAL AND
      METHODS: We retrospectively studied 66 sequential and 63 gastric biopsies from 66
      patients fulfilling the histological diagnosis of "esophagitis". Cases were
      arranged in two groups: G1 (H. pylori negative): N = 44 (27 m; 17 f), mean age
      7.3 y (range 7-9 m-18 y) and G2 (H. pylori positive): N = 22 (16 f; 6 m), mean
      age 12.8 y (range 7-16 y). RESULTS: The bases for performing endoscopy and
      biopsies were as follows: in G1 (N44) symptoms of gastroesophageal reflux (GER)
      in 24 cases and non-GER in 20 cases; in G2 (N = 22): symptoms of GER in 13 and
      non-GER in 9 cases. Esophageal endoscopic findings for G1 patients included:
      normal mucosa 39; esophagitis 3; congestive mucosa and esophagitis 1 each.
      Stomach endoscopic findings for G1 patients were normal mucosa 29; nodular antrum
      7; congestive mucosa 4; ulceration 2; unknown 2. G2 children revealed nodular
      antrum 19; congestive antrum 2; normal mucosa 1. Histology of esophageal biopsies
      in G1 was esophagitis grade 1,35; grade 2,4; grade 3, 4, and grade 5, 1. G2
      showed esophagitis grade 1,20, and grade 2,2. The histologic findings of the
      gastric biopsies were as follows: G1 (N = 41): normal mucosa 23; mild chronic
      gastritis 6; mucus depletion in the superficial 5; mild acute gastritis 3;
      hemorrhage 1; insufficient tissue 3. G2: chronic gastritis associated with H.
      pylori with or without follicular hyperplasia 21; mild gastritis 1.

PMID- 11577568
TI  - Inflammatory bowel diseases. Misery needn't be the norm.

PMID- 11577569
TI  - Health tips. Reducing excess gas.

PMID- 11577570
TI  - Phytoestrogens--plant-based alternative to HRT?

PMID- 11577572
TI  - EECP. Putting the squeeze on chest pain.

PMID- 11577571
TI  - Test helps predict recurrent prostate cancer.

PMID- 11577573
TI  - Sudden hearing loss. Prompt evaluation is key.

PMID- 11577574
TI  - Acupuncture. Procedure is gaining acceptance.

PMID- 11577575
TI  - I sweat excessively, even when the weather is cool and I'm just spending a quiet
      day indoors. What can I do?

PMID- 11577576
TI  - Since retiring, I've enjoyed traveling and trying new foods. But over the last
      few months, food just hasn't tasted the same. The flavors seem dull. What might
      cause this?

PMID- 11577577
TI  - [Complications in kidney transplantation].
AB  - DE NOVO DIABETES AND CARDIOVASCULAR RISK: Certain kidney transplant recipients
      who develop de novo diabetes have an unfavorable cardiovascular risk profile,
      comparable to patients with type 2 diabetes mellitus, with advanced age,
      dyslipidemia, obesity and high blood pressure. MYOCARDIAL INFARCTION IN THE
      PERIOPERATIVE PERIOD: Among kidney transplant recipients, those whose risk
      factors include male gender diabetes, age over 50 years and prior
      revascularization procedure for coronary artery disease have a higher risk for
      myocardial infarction in the perioperative period. The usefulness of
      anticoagulant or beta-blockers as preventive treatment for these high-risk
      patients remains to be determined. HYPERLIPIDEMIA: A retrospective analysis of
      530 kidney transplant recipients demonstrated that a very significant proportion
      of those with dyslipidemia are not receiving appropriate care although their
      lipid profile is indicative of a high or very high cardiovascular risk. MASSIVE
      PROTEINURIA: An angiotensin II inhibitor, losartan, has been found to be
      effective against massive proteinuria (> 3.5 g/l) occurring after kidney
      transplantation. CALCINEURIN-INHIBITOR-INDUCED HEMOLYTIC UREMIA SYNDROME: Five to
      ten percent of patients given calcineurin inhibitors develop a hemolytic uremia
      syndrome. Sirolimus appears to be a very interesting alternative for
      immunoprophylaxys against acute rejection.

PMID- 11577578
TI  - [Viral infections in renal transplantation].
AB  - KIDNEY TRANSPLANTATION IN HIV-POSITIVE SUBJECTS: To date, HIV+ patients have
      generally been excluded from transplantation programs. Encouraging results have
      however been obtained in 6 patients suggesting that transplantation and the
      accompanying immunosuppression are feasible in selected HIV-positive patients.
      HUMAN POLYOMAVIRUS INFECTIONS: Polyomavirus BK has been implicated as the
      pathogenic agent causing tubulointerstitial nephropathies in less than 5% of all
      kidney graft recipients. Polyomavirus JC, the causal agent of progressive
      multifocal leucoencephalitis, appears to be a co-infectant with the BK virus. Its
      pathogenic potential remains to be elucidated. POLYOMAVIRUS-LINKED PROBLEMS: It
      is very difficult to make the histological diagnosis of polyomavirus nephropathy
      due to the presence of several disease stages: the basic question is to
      distinguish between acute rejection and BK virus nephropathy. Excessive
      immunosuppression appears to be an predominant factor leading to BK virus
      infection of the kidney graft, sometimes leading to loss of the graft. It is thus
      a general rule to reduce the immunosuppression in patients with BK virus
      nephropathy. EPSTEIN-BARR VIRUS INFECTIONS: Epstein-Barr infections often lead to
      posttransplantation lymphoproliferative disorders that can be diagnosed early
      using quantitative polymerase chain reaction (PCR). PCR is also useful for
      measuring viral load and for adapting treatment.

PMID- 11577579
TI  - [Focus on Islets of Langerhans transplantation].
AB  - INDICATIONS: There are two types of indications for Langerhans islets
      transplantation, patients with type 1 diabetes mellitus who have a functional
      kidney graft but who cannot be candidates for total pancreas transplantation, and
      soon, patients without renal failure who develop particularly uncontrollable
      diabetes mellitus. SEVERAL BASIC CONDITIONS: Several conditions are required for
      the success of Langerhans islet transplantation: a laboratory with demonstrated
      skill is isolating islets, a sufficiently large number of islets for injection
      (600,000 for a 60-kg patient), fresh islets harvested within less than 24 hours
      before transplantation, effective immunosuppressive treatment with no toxic
      effect on Langerhans islets. The injection is a simple procedure performed under
      local anesthesia via transhepatic catheterization of the portal vein. RESULTS:
      Through 2000, 10% to 20% of implanted grafts were functional at 1 year. Islets
      survival has exceeded 80% at 1 year. The gold standard for success is withdrawal
      of insulin therapy and normal glucose control. Islets grafts will undoubtedly
      become the next important step in the treatment of type 1 diabetes mellitus, but
      other techniques are also envisaged for the future.

PMID- 11577580
TI  - [Prevention and treatment of type 1 diabetes].
AB  - LANGERHANS ISLET TRANSPLANTATION: Early results have been promising with insulin
      production in all cases two years after transplantation. These encouraging
      results have been obtained with a specifically designed protocol for islet
      harvesting, immunosuppression and transplantation of a large quantity of islets
      from several donors. EARLY IMMUNOSUPPRESSION: Since diabetes mellitus type 1 is
      an autoimmune disease, immunosuppression could be a most interesting
      etiopathological solution. Results obtained both in mouse models and in humans
      given monoclonal humanized anti-lymphocyte T antibodies (hOKT3 gamma 1) during
      the first 6 weeks following diagnosis have been quite encouraging. TWO APPROACHES
      TO GENE THERAPY: For the first, the goal is to improve the transplantation
      technique by isolating the islets in vitro in an attempt to improve their
      function via ex vivo transfection of different genes. The second approach aims at
      treatment of the complications of diabetes, particularly lower limb arteritis and
      coronary artery disease. Here the vector is an adenovirus carrying a gene coding
      for VEGF, a growth factor with proangiogenic action.

PMID- 11577581
TI  - [Liver transplantation and living donors].
AB  - LIVER SPLITTING: Classically, cadaver livers are split ex situ to provide two
      grafts for transplantation. This procedure could be performed in situ, limiting
      the duration of the operation and improving recovery of liver function. LIVING
      RELATED DONORS: Living donor liver transplantation is a well established
      technique in children. Donor mortality is nil and morbidity very acceptable. For
      adults, the results have been less satisfactory with increasing risk for the
      recipient, with biliary and venous problems due to the "small-for-size" implant.
      ORGAN HARVESTING: The left lobe, classically used for children, can also be
      grafted into adults, but under certain restrictive conditions. If the donor's
      residual liver volume is below 0.8% of the total body mass, the biological
      alterations remain limited and transient. EMERGENCY TRANSPLANTATIONS: Liver
      transplantations using a living donor can save critically ill patients with a
      life expectancy of less than 3 months. Remarkable survival rates have been
      achieved.

PMID- 11577582
TI  - [Specific experiences in females receiving an organ transplant].
AB  - CONTRACEPTION: As in women who do not have a heart transplant, contraception is
      never perfect, irrespective of the method, intrauterine device (risk of
      infection), estrogens, progestogens. PREGNANCY: Besides the general effects also
      observed in all pregnant women, pregnancy in the heart transplant recipient also
      carries the risk of cytomegalovirus infection and preeclampsia.
      IMMUNOSUPPRESSION: Cyclosporin or azathioprine are generally indicated, depending
      on the individual risks. PREVENTION OF BONE DISEASE: Advice concerning diet and
      lifestyle should be given prior to transplantation in order to reduce the risk of
      osteoporosis and osteomalacia. Bone density, particularly of the femoral neck, is
      essential for screening. A rheumatology examination is also quite useful. CANCER:
      De novo cancer is favored by the use of antilymphocyte inductors. Most are breast
      cancers (mean delay 60 months); other gynecology cancers develop after about 50
      months. The risk of recurrence in patients who had breast cancer is highest
      during the first 2 years. The risk of recurrent uterine cancer is constantly
      observed.

PMID- 11577583
TI  - [Ischemia-reperfusion].
AB  - IMPORTANCE OF ISCHEMIA-REPERFUSION LESIONS: After transplantation, ischemia
      reperfusion lesions are associated with an increased risk of acute rejection,
      late recovery of liver function, or chronic graft dysfunction. In all, about 20%
      of the grafts are lost. The importance of prevention is evident. HEME-OXYGENASE:
      It has been shown that heme-oxygenase, an anti-oxidant reducing apoptosis,
      reduces the extent of ischemia-reperfusion lesions after liver, heart, kidney or
      Langerhans islet transplantation. OTHER COMPOUNDS WITH INTERESTING PROPERTIES:
      Other compounds also have interesting properties for preventing ischemia
      reperfusion lesions: a specific metallo-protease inhibitor, L-arginine, a
      selective agonist of the PGE1 receptor, estrogens, low-dose cyclosporine, and
      certain immunosuppressors (FTY 720, anti CD28, anti B7-1), and rPSGL-Ig ligand.

PMID- 11577584
TI  - [Chicago 2001. What impressions to take from Chicago 2001?].

PMID- 11577585
TI  - [Allorecognition].
AB  - TWO TYPES OF RECOGNITION: Direct recognition occurs when the recipient's T cells
      recognize allogenic antigens presented by the donor antigen presenting cells.
      Indirect recognition occurs when donor antigens on recipient antigen presenting
      cells are recognized. DIRECT RECOGNITION: Direct recognition occurs during the
      first days or weeks after transplantation when naive recipient cells recognize
      donor dendritic cells that have migrated to secondary lymphoid organs. This
      explains why acute rejection occurs mainly during the first weeks after
      transplantation. INDIRECT RECOGNITION: This is certainly a less intense mechanism
      than direct recognition. It probably is involved in acute rejection but is known
      to play a major role in chronic rejection. CD4 cells that have been activated by
      indirect recognition play an essential role in activating B cells, leading to the
      formation of anti-HLA antibodies as well as in activating macrophages and
      monocytes, endothelial cells and smooth muscle cells. INDUCTION OF TOLERANCE:
      Three mechanisms of action for regulating the allo-immune response leading to
      graft tolerance have been put forward: consumption of interleukin-2, production
      of suppressive cytokins, direct or indirect suppressive contact. T CELL
      ACTIVATION: Knowledge of the intracellular signals induced by T cell receptor
      activation makes it possible to target key proteins that could be blocked leading
      to better immunosuppression than with calcineurin inhibition.

PMID- 11577586
TI  - [mTOR and FTY 720 inhibitors].
AB  - SIROLIMUS: The leading member of the mTOR inhibitor family, sirolimus or
      rapamycin, has dose-dependent side effects that can generally be well controlled.
      Sirolimus can be combined with tacrolimus at therapeutic doses; likewise for the
      sirolimus-cyclosporine combination at moderate dosage. Effective plasma
      concentrations of sirolimus vary from 5 to 20 ng/ml depending on the combination
      of immunosuppressant agents used. Sirolimus has been shown to inhibit metastatic
      diffusion of renal adenocarcinoma in the mouse. Its complex side effects on
      angiogenesis, fibrosis processes and chronic rejection are still being
      investigated. EVEROLIMUS: Everolimus, or RAD, has a very short half-life, but
      induces fewer hematologic effects. The therapeutic dose must reach at least 3
      ng/ml to prevent rejection. Doses above 15 ng/ml increase the risk of
      thrombocytopenia. FTY 720: A new immunosuppressant agent, FTY 720, does not
      belong to any known family. It has a totally different mechanism of action
      compared with currently available immunosuppressants. FTY 720 increases the
      expression of chemokine receptors on the surface of T cells making them
      unavailable for the rejection reaction. FTY 720 has a very long half-life (108
      hours). Due to its particular liver metabolism, there is a very low risk of drug
      interactions.

PMID- 11577587
TI  - [Immunosuppression, ongoing clinical trials].
AB  - MONOCLONAL ANTIBODIES: Monoclonal antibodies have been humanized to improve their
      duration of action and their tolerance. Lymphocyte-depleting humanized anti-CD3
      antibodies are globally well tolerated. Coupled with an immunotoxin, Campath 1H,
      a humanized anti-CD3 antibody with specific anti-CD52 depleting properties which
      also depletes immunocompetent cells, is being tested. There is increasing
      interest in the use of monoclonal antibodies in combination with rapamycin.
      SIROLIMUS AND EVEROLIMUS: The half-life of sirolimus is twice that of everolimus.
      Otherwise quite similar, these compounds have dose-dependent side effects:
      leukopenia, thrombocytopenia, hyperlipidemia. There use allows a lower dosage for
      the calcineurin inhibitor. Sirolimus is particularly active in reducing intimal
      proliferation within the vessel walls. Precise indications at the present time
      include induction of tolerance, withdrawal of the calcineurin inhibitor, use of
      low-dose calcineurin inhibitor, and corticosteroid withdrawal. ELIMINATING THE
      SIDE EFFECTS OF CORTICOSTEROIDS: Complications resulting from the use of
      corticosteroids, particularly bone complications, are still a problem with the
      low doses used in long-term regimens for transplant recipients. Several means
      have been proposed to reduce the risk. Total withdrawal is possible, but the risk
      of an increased rate of acute rejection limits indications. It appears that total
      withdrawal then complete abstention is not compatible immunologically.
      IMMUNOSUPPRESSORS IN PERSPECTIVE: Three groups of compounds have immunosuppressor
      potential: anti-adhesion molecule antibodies, co-stimulation blockers, and
      molecules inhibiting T-lymphocyte activators and their signalization factors.

PMID- 11577588
TI  - [Antibodies and immunomodulation].
AB  - CURRENT SITUATION: When examining immunosuppressor induction one important
      question is to determine the efficacy of anti-CD25 antibodies or the new compound
      efalizumab compared with anti-lymphocyte globulins and anti-OKT3 agents known to
      be very effective but with important side effects. DACLIZUMAB: Recent work has
      shown that 2 injections at 1 mg/kg (one on day 1 the other between day 10 and day
      14) completely block interleukin-2 receptor for more than 10 weeks in 98% of the
      recipients. Instead of the 5 injections every 15 days as indicated by the
      recommendations, this new protocol is easier to institute and less costly. The
      efficacy remains to be demonstrated. BASILIXIMAB: This chimeric monoclonal
      antibody has affinity for the IL-2 receptor. Balisiximab is administered in 2
      doses at 20 mg, one on day 0 and the other one on day 4. A unique 40 mg dose on
      day 1 has a comparable efficacy. OTHER PROTOCOLS: Among the different induction
      molecules with promising properties, particular attention should be given to
      efalizumab. The antisense oligonucleotide (ICAM-1; ISIS 2302) appears to show
      relatively poor tolerance and no therapeutic efficacy. In association with
      plasmapheresis and intravenous immunoglobulins, it has been shown to be very
      effective when given to graft candidates with a positive cross match or after
      transplantation in case of acute rejection.

PMID- 11577589
TI  - [Minimization of immunosuppression].
AB  - Minimization protocols: The goal of minimization protocols is to reduce the load
      of immunosuppressant agents after transplantation. Besides the basic medical
      objective of reduced deleterious effects of long-term immunosuppression,
      minimization also has an economic impact. Discontinuation of corticosteroid
      therapy: Results obtained with different minimization protocols have shown that
      any interruption of corticosteroid therapy, even if associated with the new
      immunosuppressants, should be conducted carefully in selected patients, tapering
      off late after transplantation. Mycophenolate-mofetil (MMF): MMF withdraw may be
      risked and the beneficial effect of discontinuation remains to be demonstrated.
      Calcineurin inhibitors: Most immunosuppression protocols use cyclosporine. The
      benefit obtained by totally discontinuing cyclosporine in stabilized patients
      does not outbalance the risks induced by withdrawal. However, in this population,
      MMF can be useful for tapering down cyclosporine. In patients with altered renal
      function, introduction of MMF or sirolimus can allow a reduction in dosage or
      complete withdrawal of cyclosporine.

PMID- 11577590
TI  - [What is new on transplantation in 2001?].
AB  - IMMUNOSUPPRESSIVE THERAPY: Intravenous immunoglobulins have demonstrated their
      value for highly immunized cross-match positive transplantation candidates. Graft
      rejection during the first two post-transplantation weeks can be avoided with
      CMPATH-1H, humanized anti-CD52 monoclonal antibody, which produces major and
      persistent T- and B-cell as well as monocyte depletion. FTY 720 is well tolerated
      and has demonstrated its efficacy in preventing acute rejection. Sirolimus would
      have an antiatheromatous effect. Attempts to minimize immunosuppression should be
      followed for several months. OTHER NEW DEVELOPMENTS: There has been considerable
      interest in Langerhans islet transplantation. Work also concerns follow-up
      techniques used to diagnosis rejection. FUNDAMENTAL SCIENCE: New advances in
      basic science that should have an impact on transplantation have been made in the
      area of lymphocyte activation, toll-like receptor structures, and germinal and
      stem cells, as well as in the areas of essay methods and gene therapy.

PMID- 11577592
TI  - [Recommendations on dyslipidemias].

PMID- 11577591
TI  - [Complications in heart transplantation: diagnosis and treatment].
AB  - ACUTE REJECTION: Endomyocardial biopsy is the most reliable method to detect
      acute rejection but is an invasive procedure. Other non-invasive methods have
      been proposed including tissular Doppler ultrasonography with analysis of the
      posterior wall velocity and teletransmitted study of the intramyocardial
      amplitude of the QRS complex. Adding plasmapheresis to the conventional treatment
      is helpful in improving survival and reducing the incidence of late coronary
      disease after severe acute reflection. Plasmapheresis also has a preventive
      effect as do certain inductors such as anti-thrombocyte globulin (ATG).
      INFECTION: Opportunistic infections are the leading cause of mortality in the
      year following heart transplantation, generally related to the
      hypogammaglobulinemia. Intravenous immunoglobulins have helped reduce the
      frequency of infections. CANCER: More than 1/3 of donor cancers diagnosed after
      transplantation will be transmitted to the cardiothoracic organ recipient.
      Melanoma, choriocarcinoma and renal carcinoma with vascular effraction are the
      most transferable tumors. DIABETES: Survival at 5 years is lower in heart
      transplant recipients but at 10 years the incidence of coronary artery disease
      and infection are the same. However at 10 years, creatininemia is higher as is
      the frequency of lower limb arteropathies. RHABDOMYOLYSIS: The incidence of
      rhabdomyolysis after heart transplantation in patients treated with statin is
      much higher than in the general population, but complementary studies are needed
      to compare the muscular effects of the different statins in transplant
      recipients. CORONARY ARTERY DISEASE: Coronary artery disease of the graft is the
      leading cause of late mortality. The known risk factors can be limited by
      normalizing blood pressure and lipidemia and using ATG to prevent rejection.
      GROWTH OF THE GRAFT IN CHILDREN: Growth of the graft has been demonstrated in 17
      recipients aged less than 13 years at the time of transplantation. Growth was
      linear and followed the child's weight and height curves. Ultrasound measures
      normalized 6 months after transplantation. PREGNANCY: The graft continues to
      function normally in female heart transplant recipients during pregnancy and post
      portum. Complementary studies are needed to determine the long-term effect.

PMID- 11577593
TI  - [Hospital management and operational budget].

PMID- 11577594
TI  - [Primary hypothyroidism in the adult older than 60 years. Characteristics and
      follow-up after initiation of replacement treatment in hospital].
AB  - OBJECTIVE: Primary hypothyroidism is common in the elderly. Yet its care remains
      unclear. PATIENTS AND METHODS: Clinical, biological characteristics and outcome
      of 45 patients aged over 60 years admitted for in-hospital initiation of
      treatment for primary hypothyroidism were recorded. Causes and tolerance of
      treatment (clinical and ECG monitoring in hospital) were seek for. RESULTS:
      Initial symptoms, predominantly fatigue (84.4%), were moderate, contrasting with
      severe biological hormonal deficiency. The most common routine biological change
      was hypercholesterolemia (57.6%). Female predominance was obvious (77.8%) and the
      most usual aetiology autoimmune chronic thyroiditis. Despite variability of
      symptoms, long term follow-up demonstrates a positive response to treatment,
      including an improvement in fatigue, eye-lid swelling, bradycardia and
      overweight. This clinical improvement was achieved on an average dose of 1.22 +/-
      0.47 mg/kg/day L-T4 in order to maintain normal TSH (3.76 +/- 2.93 mUI/l).
      Cardiovascular incidents while starting treatment require experienced care and
      low dose initial treatment. CONCLUSION: Primary hypothyroidism is still lately
      discovered in the elderly. Yet, since treatment is efficacious and simple, the
      disease should be searched for and cared after whenever a related symptom occurs.

PMID- 11577595
TI  - [Autism and associated pathologies. Clinical study of 295 cases involving
      development disorders].
AB  - OBJECTIVE: Known since the first descriptions in 1943, diseases related to autism
      and associated disorders have incited a growing body of work. Both theoretical
      interrogations (what is the pathogenic role of autism?) and practical measures
      (management, screening) are implied. Nevertheless the frequency of autism-related
      disease has varied from 10 to 37% depending on the series reported. We studied
      the frequency of these factors in a population of children with major development
      disorders cared for at the Tours university hospital over a 39-month period.
      PATIENTS AND METHODS: We reviewed retrospectively the medial features of 295
      children examined in our psychiatry and neurophysiology unit for children at the
      Tours center for major development disorders (based on the DSM IV diagnostic
      criteria) between September 1995 and December 1998. We divided these factors into
      4 categories: hereditary diseases, serious medical conditions, minimal physical
      disorders and ante- or perinatal antecedents. RESULTS: Among these 295 children,
      26.5% had a proven or probable hereditary disease, 19% had a serious medical
      condition and 21.7% had minimal physical disorders. Among the children with a
      serious medical condition, 34.4% also had ante- or perinatal antecedents. Among
      the 33% without any medical factor, 77% also had ante- or perinatal antecedents.
      CONCLUSION: Our data point out the quantitative importance of medical factors
      associated with major development disorders. They imply a close multidisciplinary
      collaboration between child psychiatrists, pediatricians and geneticists in order
      to identify these disorders and develop an integrated management scheme. On a
      more theoretical level, it appears possible to identify subgroups of children
      among such a population based on associated diseases and neuropsychological
      patterns. This dimension would be useful for research into the pathogenic
      mechanisms involved.

PMID- 11577596
TI  - [Diagnostic and therapeutic management of urinary infections. Survey in the
      medical services of the hospitals south of the Marseille Hospital Center].
AB  - OBJECTIVE: The aim of this prospective study was to observe diagnostic and
      antibiotic prescribing practices in urinary tract infection disease (UTID) in
      comparison with available guidelines. PATIENTS AND METHODS: We included all
      patients hospitalized in four medical wards of the Sainte-Marguerite Hospital in
      Marseille France who suffered from UTID. RESULTS: During the study period, 60
      cases of UTID were observed, 29 were community-acquired and 31 were nosocomially
      acquired. Management of uncomplicated UTID, the most frequent type (47/60 cases),
      showed considerable divergence between practices and guidelines. Not in keeping
      with the guidelines, urinalysis reagent strips were only used for 3 of the 47
      cases. Furthermore, broad-spectrum antibiotics were prescribed as the first line
      treatment in more than 70% of the patients whereas only half of these
      prescriptions were warranted according to the guidelines. For complicated UTID
      however (13 cases) diagnostic and antibiotic prescribing practices were globally
      in accordance with the guidelines. CONCLUSION: This survey points out the
      divergence between guidelines and real management of UTID in hospitals. Clinical
      practices should be revisited to be in agreement with guidelines. Drafting
      antibiotic prescription guides explaining UTID management would be helpful for
      training future physicians.

PMID- 11577597
TI  - [Gelatinous transformation of bone marrow. 4 cases].

PMID- 11577598
TI  - [Pseudohypoaldosteronism acquired in the remnants of an ileostomy].

PMID- 11577599
TI  - [Screening methods and biological diagnosis of dyslipidemias in primary
      prevention. Recommendations for clinical practice].

PMID- 11577600
TI  - [Endoprostheses for aneurysms of the abdominal aorta. A technical innovation, a
      cultural revolution].
AB  - FACTS: A revolutionary technology has totally renovated the treatment of
      aneurysms of the abdominal aorta. Classical "dissection-graft" procedures require
      a wide abdominal incision with clamping and declamping times, and often major
      blood loss. Perioperative mortality varies from 3% to 7% depending on the team's
      experience and the presence of comorbidities. Complications occur in 30% of the
      patients; often benign they can be quite serious. As direct consequence of the
      development of peripheral stents, endoprostheses can now be introduced via the
      femoral route through a short inguinal incision. Operative trauma is considerably
      reduced, greatly shortening the recovery time. Mortality is low, of around 1%,
      and postoperative complications are much less frequent and much less severe.
      There is also a 3-fold reduction in the duration of the hospital stay.
      PREREQUISITES: All aneurysms cannot be treated with this method. The anatomy of
      the aneurysm and the iliac arteries is a determining factor. The iliac vessels
      must be large enough and devoid of important obstruction (kinks, atheromatous
      plaques) in order to access the aorta. The subrenal collar must measure at least
      1 cm and be free of severe calcifications or thrombi. A rigorous preoperative
      exploration, using CT-scan with 3D reconstruction and graduated arteriography, is
      necessary. The length and diameter of the prosthesis is calculated from the
      results and must be perfectly adapted to avoid failure. UNKNOWNS: Long-term
      outcome remains unknown. The endoprosthesis excluded the aneurysm from the blood
      stream, depressurizing the aneurysmal sac. Endoprosthetic leakage can occur in
      case of defective application or by reflux from lumbar or inferior mesenteric
      arteries or due to leakage of the endoprosthesis itself. In such cases, the
      aneurysm can continue to progress. This explains the need for careful follow-up
      with duplex Doppler and/or CT-scan in treated patients. If the treatment is
      incomplete, complementary procedures may be necessary, often via an endovascular
      route or in some cases with conversion to conventional surgery. EVALUATIONS:
      Improved prosthetic design and durability is an important point. Randomized
      studies organized in France, as well as in England and Holland and the United
      States, are currently assessing the contribution of this new technique and its
      relative role compared with conventional surgery.

PMID- 11577601
TI  - [Chronic ORL infections of the adult in the community. Role of ciprofloxacin].

PMID- 11577602
TI  - Trends in hospital emergency department utilization: United States, 1992-99.
AB  - OBJECTIVES: This report describes trends in hospital emergency department (ED)
      visits in the United States. Statistics are presented for overall utilization,
      case mix of patients, services provided, and outcome measures. METHODS: The data
      presented in this report were collected from the National Hospital Ambulatory
      Medical Care Survey (NHAMCS) from 1992 through 1999. To make the data points more
      reliable for trend analysis, the data were combined to provide 2-year annual
      averages for 1993-94, 1995-96, and 1997-98. The survey in 1992 was especially
      large so it was used alone. The 1999 data are the most recent year available and
      are presented separately. RESULTS: The volume of ED visits in the United States
      increased by 14% from 1992 through 1999, from 89.8 million to 102.8 million
      annually. This increase is mainly due to an increase in visits for illness
      related as opposed to injury-related conditions. Although the population rate for
      ED visits did not significantly increase over this time period (rates between
      35.7 and 37.9 visits per 100 persons), the rate for illness-related visits rose
      from 21.0 to 24.0 visits per 100 persons (p < 0.01). The most dramatic increases
      were observed in the overall visit rate for black persons 65 years of age and
      over, which rose by 59% from 45.4 visits per 100 persons in 1992 to 72.2 in 1999.
      For black seniors, both illness and injury-related visit rates increased at a
      much higher rate compared with trends for white seniors. CONCLUSION: Increased
      volume of ED encounters for persons 45 years of age and over was associated with
      a greater proportion of illness conditions presenting to the ED and the use of
      more services, medications, and mid-level providers.

PMID- 11577603
TI  - Cap rates show California system inching toward profit.

PMID- 11577604
TI  - Medical costs high for depression patients who resist treatment.

PMID- 11577605
TI  - Mid-sized, large groups account for major share of capitation.

PMID- 11577606
TI  - Beware growing utilization of emergency room by seniors.

PMID- 11577607
TI  - New analysis suggests plans, providers rethinking capitation.

PMID- 11577608
TI  - [Initial results and long-term outcome of percutaneous coronary intervention in
      patients with previous coronary artery bypass grafting].
AB  - OBJECTIVES: The incidence of percutaneous coronary intervention following bypass
      surgery(coronary artery bypass grafting: CABG) is not low, but the outcomes of
      patients requiring percutaneous coronary intervention after CABG are not well
      known. METHODS: From June 1970 to June 2000, 2,981 patients underwent CABG at our
      institute using 6,747 grafts including 2,875 saphenous vein graft(SVG), 3,042
      internal thoracic artery(ITA), 706 gastro-epiploic artery(GEA), 122 radial
      artery(RA), and 2 others. Three hundred twenty-seven patients underwent
      subsequent percutaneous coronary intervention in 520 lesions(104 SVG, 97 ITA, 12
      GEA, 8 RA, 299 native artery). The initial results and long-term outcome
      following percutaneous coronary intervention in these 520 consecutive procedures
      were evaluated retrospectively. RESULTS: Percutaneous coronary intervention to
      arterial grafts were performed mainly within the early post-operative period,
      whereas percutaneous coronary intervention to vein grafts had two periodic peaks
      in the early post-operative period and at 7 years after CABG. Procedural success
      rate of percutaneous coronary intervention was 90% for SVG, 81% for ITA, 58% for
      GEA, 88% for RA, and 87% for native arteries. Restenosis rate was 56% for SVG,
      30% for ITA, 83% for GEA, 83% for RA, and 49% for native arteries. Cardiac events
      after percutaneous coronary intervention with previous CABG were greater in cases
      of ITA, followed by native arteries, SVG, GEA and RA(p = 0.0046). In the early
      post-operative period, there was no significant difference between ITA and SVG.
      In the chronic stage, the prognosis of cardiac events after PCI for SVG was worse
      than for ITA. CONCLUSIONS: Percutaneous coronary intervention after CABG requires
      strategic consideration based on target-specific initial results and long-term
      outcome.

PMID- 11577609
TI  - [Usefulness of combination post-stress dysfunction and perfusion imaging in
      technetium-99m-tetrofosmin myocardial scintigraphy].
AB  - OBJECTIVES: Myocardial perfusion imaging has lower sensitivity for the diagnosis
      of coronary artery disease in patients with three-vessel disease. The presence of
      post-stress dysfunction of the left ventricle, evaluated by
      electrocardiography(ECG) gated single photon emission computed tomography(SPECT)
      with a quantitative gated SPECT program, was investigated in patients with
      coronary artery disease, and also whether combining post-stress dysfunction and
      myocardial perfusion imaging improved the diagnosis of coronary artery disease.
      METHODS: ECG gated technetium-99m-tetrofosmin SPECT was performed using a one
      day, stress and rest, protocol in 139 patients. SPECT and coronary angiography
      were performed within 1 month. The coronary artery disease group consisted of 89
      patients: 43 with one-vessel disease(1VD), 28 with two-vessel disease(2VD), and
      18 with three-vessel disease(3VD). The group with zero-vessel disease(0VD)
      consisted of 50 patients. According to post-stress and rest ejection fraction(EF)
      and end-systolic volume (ESV), post-stress dysfunction is defined as follows:
      rest EF--post-stress EF > or = 5% and post-stress ESV--rest ESV > or = 5 ml.
      RESULTS: In the coronary artery disease group, post-stress ESV was larger than
      rest ESV(37.8 +/- 26.4, 34.0 +/- 24.2 ml, p < 0.001), and post-stress EF was
      lower than rest EF (61.5 +/- 11.1%, 64.2 +/- 10.8%, p < 0.001). In the 0VD group,
      ESV and EF were the same for post-stress and rest (25.7 +/- 20.8, 26.2 +/- 21.6
      ml, NS; 70.4 +/- 9.5%, 70.0 +/- 9.6%, NS). Post-stress dysfunction was 6.0% in
      the 0VD group and 30.3% in the coronary artery disease group(p < 0.001).
      Furthermore, post-stress dysfunction in the 2VD (35.7%) and 3VD(38.9%) groups was
      higher than that in the 0VD group(p < 0.01, p < 0.01). Sensitivity of coronary
      artery disease diagnosis by myocardial perfusion imaging was 75%. The combination
      of post-stress dysfunction and myocardial perfusion imaging improved sensitivity
      from 75% to 82%(p < 0.05), but reduced the specificity from 92% to 86%(p = 0.08).
      CONCLUSIONS: Post-stress dysfunction is a useful parameter for clinical diagnosis
      of coronary artery disease.

PMID- 11577610
TI  - [Prognostic significance of myocardial imaging with iodine-123 beta-methyl-p
      iodophenyl-pentadecanoic acid in patients with angina pectoris].
AB  - OBJECTIVES: To assess the clinical significance of iodine-123 beta-methyl-p
      iodophenyl-pentadecanoic acid(BMIPP) single photon emission computed
      tomography(SPECT), the predictive value of BMIPP imaging in patients with angina
      pectoris was evaluated. METHODS: One hundred seventy-four patients who underwent
      BMIPP imaging in our institution were aged 61.8 +/- 11 years. One hundred thirty
      five patients had stable angina and 39 had unstable angina at the time of
      examination. Patients with previous myocardial infarction or myocardial disorders
      were excluded. Early and delayed images were acquired in BMIPP SPECT, and the
      images were analyzed visually. Cardiac events were classified into hard and soft
      events: the former consisted of cardiac death and nonfatal myocardial infarction,
      and the latter included coronary revascularization and heart failure. RESULTS:
      The findings of BMIPP imaging were normal in 82 patients and abnormal in 92.
      During follow-up of 15.5 +/- 9.5 months, hard events were observed in 4 patients
      and soft events in 53. In patients with normal BMIPP imaging, soft events were
      observed in nine patients, but no hard event was encountered. Furthermore, in
      patients with both normal BMIPP and stress thallium imagings, no cardiac event
      was observed during 2 years. In contrast, 4 hard events and 44 soft events
      occurred in patients with abnormal BMIPP imaging. Patients with abnormal BMIPP
      imaging had a higher incidence of soft events than those with normal BMIPP
      imaging, regardless of the type of angina(16/62 vs 3/73, p < 0.0005 for stable
      angina; 28/30 vs 6/9, p < 0.0001 for unstable angina). CONCLUSIONS: The finding
      of BMIPP imaging correlates well with the mid-term prognosis of patients with
      angina pectoris. Since BMIPP SPECT is performed without stress to the patient,
      this imaging modality is important in evaluating patients with stable or unstable
      angina.

PMID- 11577611
TI  - [Significance of soluble thrombomodulin in the coronary circulation of patients
      with coronary artery disease].
AB  - OBJECTIVES: The relationship between plasma levels of soluble thrombomodulin, a
      probable marker for endothelial damage, and the severity of coronary
      atherosclerosis was investigated. METHODS: Plasma soluble thrombomodulin levels
      were evaluated in 160 patients(mean age 62 +/- 11 years) who underwent coronary
      angiography. Blood samples were obtained from the peripheral vein, ostium of the
      left coronary artery and coronary sinus. The levels of plasma thrombomodulin were
      measured by enzyme-linked immunosorbent assay. The change of thrombomodulin level
      in the coronary circulation (delta TM) was calculated as the coronary sino
      arterial difference. Patients were classified into four groups according to the
      number of diseased vessels, and the severity of coronary atherosclerosis was
      evaluated with the modified Gensini score. RESULTS: Coronary sinus levels of
      thrombomodulin were significantly higher in the two or more vessel disease(VD)
      groups than in the no or one VD groups(p < 0.05). delta TM were significantly
      higher in the 2VD than in the 0VD groups(p < 0.05), and higher in the 3VD than in
      the 0VD or 1VD groups(p < 0.05). delta TM showed positive correlation with
      Gensini score for left coronary arteries(r = 0.347, p < 0.0001). CONCLUSIONS: The
      increment of thrombomodulin across the coronary circulation was significantly
      correlated with the severity of coronary atherosclerosis, suggesting a close
      association between the progression of coronary atherosclerotic stenosis and
      damage to the endothelial surface.

PMID- 11577612
TI  - [Three-dimensional transesophageal echocardiographic measurement of left
      ventricular volumes using the average rotation method: comparison with the disk
      summation method].
AB  - OBJECTIVES: Three-dimensional(3-D) echocardiography accurately calculates left
      ventricular volumes without geometric assumptions. Conventional 3-D
      echocardiography using the disk summation method is limited in practical use
      because of the long analysis time. This study validated the average rotation
      method for rapid and accurate left ventricular volume measurement compared with
      the conventional disk summation method. METHODS: 3-D data acquisition using
      multiplane transesophageal echocardiography was performed in 13 patients. Left
      ventricular volumes and ejection fraction were calculated by the disk summation
      method with 20 parallel short-axis tomograms and by the average rotation method
      with 3, 6, 9 and 12 apical long-axis tomograms. RESULTS: 3-D left ventricular
      volumes and ejection fraction by the average rotation method in each subgroup of
      slice resolution had excellent correlation and close limits of agreement with
      those by the disk summation method. Intraobserver variability and interobserver
      variability were < or = 11%. With the use of three component tomograms, analysis
      time required for left ventricular volume measurement by the average rotation
      method was < or = 2 min. CONCLUSIONS: Transesophageal 3-D echocardiography using
      the average rotation method is a clinically useful tool for accurate and rapid
      measurement of left ventricular volume and function.

PMID- 11577613
TI  - [Isolated cerebral and myocardial perfusion during aortic arch repair in
      neonates].
AB  - OBJECTIVES: To prevent possible neurologic injury after hypothermic circulatory
      arrest, aortic arch obstruction with cardiac defects is repaired in one stage
      using isolated cerebral and myocardial perfusion (ICMP). This study investigated
      serum S-100 protein(S-100) levels in neonates undergoing ICMP. METHODS: Between
      February 2000 and January 2001, 19 neonate patients underwent repair of critical
      congenital heart defects. Seven of these patients with aortic coarctation(n = 3)
      or interrupted aortic arch (n = 4) with ventricular septal defect(ICMP group)
      underwent primary total repair. An arterial cannula was inserted either into the
      ascending aorta or into a polytetrafluoroethylene graft which was anastomosed to
      the innominate artery. During arch repair, a cross-clamp was placed between the
      innominate and left carotid arteries, and an end-to-end arch anastomosis was
      performed with cerebral perfusion and heart beating. During ICMP the flow was
      reduced to maintain a radial artery pressure of 30-45 mmHg. The remaining 12
      patients underwent complete transposition of great arteries(n = 9) or total
      anomalous pulmonary venous connection(n = 3) using a cardiopulmonary bypass(CPB)
      with flow of 150-180 ml/kg/min(control group). Sequential blood samples for S-100
      determinations were taken after induction of anesthesia, 30 min after aortic
      declamping(post-ACC), 30 min after CPB, and 24 hr after CPB. RESULTS: There were
      no early and late deaths. Neurologic symptoms were not observed in any patients.
      Mean ICMP time in ICMP group was 17 +/- 4 min. In all patients, S-100 showed the
      highest value post-ACC and then declined with time. There were no differences in
      S-100 between the groups at any other time point. CONCLUSIONS: Selective cerebral
      perfusion through the innominate artery may be able to maintain brain
      circulation.

PMID- 11577614
TI  - Effect of interatrial block on left atrial function.
AB  - Interatrial block produces prolonged P-waves due to conduction delay mainly in
      the Bachmann bundle, the most direct route from right to left atrium. It is
      prevalent in patients over age 60 with its main clinical significance its
      association with eventual atrial fibrillation and/or flutter. Having demonstrated
      a mean delay in the onset of active left ventricular filling of 37 msec, we
      defined the electromechanical abnormality further by measuring left atrial volume
      at key points in the atrial cycle to produce 10 measurements of left atrial
      function. Compared to the normal left atrium, interatrial block is correlated
      with a large, poorly contractile left atrium with a delayed and markedly reduced
      contribution to left ventricular filling and the kinetic energy with which atrial
      systole propels blood.

PMID- 11577615
TI  - [A case of congestive heart failure with concentric hypertrophy. Resolution of
      remarkable myocardial edema in a patient with acute myocarditis].

PMID- 11577616
TI  - Target detection in scientific visualization.
AB  - Three experiments were conducted to test participants' ability to detect targets
      in colored spatial displays using 7-level bipolar scales. Experiment 1 assessed
      the ability of participants to detect high or low targets using 12 scales whose
      poles either were directly opposed in color space or had a primary and an
      intermediate hue at each pole. Experiment 2 used 8 scales whose arms were
      orthogonal in color space. Experiment 3 examined the simultaneous detection of
      high and low targets. Although there are notable exceptions, scales that are
      close to or above the horizontal (red-green) axis in color space perform best. Of
      the scales with orthogonal arms, those that are oriented downward, toward the
      blues, in color space are least satisfactory. Scales that are asymmetrically
      effective are common, and applications requiring good detectability at both
      extremes must take this into account. The results are discussed in the context of
      the evolution of trichromatic color vision.

PMID- 11577617
TI  - Children's eyewitness reports after exposure to misinformation from parents.
AB  - This study examined how misleading suggestions from parents influenced children's
      eyewitness reports. Children (3 to 8 years old) participated in science
      demonstrations, listened to their parents read a story that described experienced
      and nonexperienced events, and subsequently discussed the science experience in
      two follow-up interviews. Many children described fictitious events in response
      to open-ended prompts, and there were no age differences in suggestibility during
      this phase of the interview. Accuracy declined markedly in response to direct
      questions, especially for the younger children. Although the older children
      retracted many of their false reports after receiving source-monitoring
      instructions, the younger children did not. Path analyses indicated that
      acquiescence, free recall, and source monitoring all contribute to mediating
      patterns of suggestibility across age. Results indicate that judgments about the
      accuracy of children's testimony must consider the possibility of exposure to
      misinformation prior to formal interviews.

PMID- 11577618
TI  - Coherent probability from incoherent judgment.
AB  - People often have knowledge about the chances of events but are unable to express
      their knowledge in the form of coherent probabilities. This study proposed to
      correct incoherent judgment via an optimization procedure that seeks the
      (coherent) probability distribution nearest to a judge's estimates of chance.
      This method was applied to the chances of simple and complex meteorological
      events, as estimated by college undergraduates. No judge responded coherently,
      but the optimization method found close (coherent) approximations to their
      estimates. Moreover, the approximations were reliably more accurate than the
      original estimates, as measured by the quadratic scoring rule. Methods for
      correcting incoherence facilitate the analysis of expected utility and allow
      human judgment to be more easily exploited in the construction of expert systems.

PMID- 11577619
TI  - Changing beliefs about implausible autobiographical events: a little plausibility
      goes a long way.
AB  - Three experiments investigated the malleability of perceived plausibility and the
      subjective likelihood of occurrence of plausible and implausible events among
      participants who had no recollection of experiencing them. In Experiment 1, a
      plausibility-enhancing manipulation (reading accounts of the occurrence of
      events) combined with a personalized suggestion increased the perceived
      plausibility of the implausible event, as well as participants' ratings of the
      likelihood that they had experienced it. Plausibility and likelihood ratings were
      uncorrelated. Subsequent studies showed that the plausibility manipulation alone
      was sufficient to increase likelihood ratings but only if the accounts that
      participants read were set in a contemporary context. These data suggest that
      false autobiographical beliefs can be induced in clinical and forensic contexts
      even for initially implausible events.

PMID- 11577620
TI  - Skilled anticipation in real-world tasks: measurement of attentional demands in
      the domain of tennis.
AB  - Anticipatory skills are characteristic of expert performance in a range of
      dynamic domains. However, models of the processes underlying such skilled
      anticipation remain limited. This study describes the construction and validation
      of a video-based test of anticipation in tennis and examined whether video test
      performance is less attentionally demanding for expert tennis players than for
      novices. Expert players performed the anticipation test more effectively than
      novices and were less vulnerable to dual-task decrement. This article discusses
      these findings in relation to models of skilled anticipation. The video test
      could be used for both selection and identification of training needs.

PMID- 11577621
TI  - Learning by imagining.
AB  - Five experiments were conducted to investigate the relative effectiveness of 2
      alternative instructional strategies. Students who were engaged in studying
      worked examples that emphasized understanding and remembering procedures and
      concepts were compared with students who were engaged in imagining worked
      examples that emphasized imagining procedures and concepts. It was hypothesized
      that students who held prerequisite schemas would find imagining to have a
      beneficial effect on learning, compared with studying the material, whereas
      students who were less knowledgeable would find imagining to have a negative
      effect on learning, compared with studying. Experimental results were in accord
      with our hypotheses. It was concluded that, under specific circumstances,
      encouraging students to imagine procedures and concepts can substantially
      facilitate learning.

PMID- 11577622
TI  - Controversies in preterm neonatal transfusions of red blood cells.

PMID- 11577623
TI  - Active isomer medications: new and improved or just repackaged?

PMID- 11577624
TI  - A Haitian rotation.

PMID- 11577625
TI  - Professionalism meets commercialism--conflict, coexistence, or capitulation?

PMID- 11577626
TI  - Time to increase pneumovac rates.

PMID- 11577627
TI  - Leaders in medicine. Ray V. McIntyre, MD.

PMID- 11577628
TI  - Cerebrospinal fluid rhinorrhea: an unusual presentation of domestic violence.
AB  - The incidence of "battered woman syndrome" is increasing over the past few years
      affecting as many as one in every four families. Most of these cases present to
      the emergency room with mostly head and maxillofacial injuries. We are describing
      three cases of battered women with cerebrospinal fluid rhinorrhea as the only
      presenting symptom of domestic violence. The different etiologies, work up and
      treatment strategies are all discussed and reviewed.

PMID- 11577629
TI  - A study to determine the accuracy of a computerized algorithm for interpretation
      of EEGs.
AB  - The main use of computerized EEG has been in sleep studies. A comprehensive
      system of interpreting routine EEGs by computers has not yet been developed and
      is technically difficult. We have tried to incorporate computers in the analysis
      and interpretation of EEGs by using information obtained from visual analysis of
      EEG in the present work. The purpose of this study was to determine the accuracy
      of such an algorithm. An electroencephalographer visually analyzed routine EEGs
      and the data was entered into an EEG Worksheet. The electroencephalographer then
      interpreted the data and a report was dictated and transcribed. Data from the EEG
      Worksheet was entered into a computer for interpretation, clinical correlation,
      and report preparation. Results indicate that the algorithm used with the EEG
      Worksheet can correctly interpret and clinically correlate visually-analyzed EEG
      data entered into a computer and reduce time for EEG report generation.

PMID- 11577630
TI  - Ready or not, hand-held prescribing is coming.
AB  - Medication prescribing errors and adverse drug events are a major cause of
      illness in the United States. Computer-assisted prescribing has been shown to
      reduce the morbidity and mortality associated with these iatrogenic occurrences.
      In the past, the technology was not readily available for system-wide
      implementation. With the recent advances in wireless and hand-held technology,
      however, the opportunity now exists for physicians to take the next step in
      improving patient care. Steps should therefore be taken by the medical community
      to systematically begin implementing a comprehensive, fully integrated computer
      assisted prescribing system.

PMID- 11577631
TI  - Professional courtesy in today's healthcare environment.

PMID- 11577632
TI  - Physicians' campaign for a healthier Oklahoma. Evaluation of the schools for
      healthy lifestyles: program overview and baseline results.

PMID- 11577633
TI  - Stomatognathic Protective Orthotic: a new dental splint utilized with an
      objective diagnosis and outcome monitoring technique.

PMID- 11577634
TI  - Lower incisor and second molar extraction in Class III treatment.
AB  - Although not fully accepted as routine orthodontic therapy, second molar and
      lower incisor extraction is well documented in the literature. The following
      cases show how both procedures can be used successfully to simplify the treatment
      of Class III malocclusion, while preserving the facial profile.

PMID- 11577635
TI  - Condylar fractures treatment in children and youths: influence on function and
      face development (a five year retrospective analysis).
AB  - To evaluate relationship between consequences of TMJ fractures in children and
      disturbed facial skeleton growth, 46 children (18 girls, 28 boys), who were 14
      years of age or younger and had undergone combined clinical and radiolographic
      examination for five years were retrospectively analyzed. Imaging studies were
      performed to investigate symptoms that included, either individually or in
      various combinations, pain, mechanical TMJ disfunction and facial skeleton
      abnormalities. The children were divided into two groups: those belonging to the
      former had been treated by functional orthopedic method alone, while the others
      had just been treated by physiotherapy. Both TMJs were normal in the patients
      treated functionally and they all showed normal facial structure, while different
      types of alterations (ranging from inflammatory to mechanical and structural
      ones) were observed in the others. We concluded that therapeutic procedures
      adopted after TMJ fractures in children are essential in minimizing consequences
      on occlusion and facial development.

PMID- 11577636
TI  - Simple, effective early treatment: bone remodeling revisited.

PMID- 11577637
TI  - Splint Helix.

PMID- 11577638
TI  - [The best way to prevent disease is by effective vaccination programs. Measles
      and polio could be eliminated].

PMID- 11577639
TI  - [Vaccine protection of Swedish children. Time for revision of replacing doses of
      diphtheria, tetanus, polio and pertussis].
AB  - The Swedish vaccination programme against diphtheria, tetanus, pertussis, polio
      and Haemophilus influenzae type b is characterized by few, widely spaced doses.
      Swedish schoolchildren have low diphtheria antibody levels compared to children
      in other countries. The introduction of acellular pertussis vaccine in 1996 has
      markedly cut the pertussis incidence in all ages except school-age children.
      There are now reasons to consider replacing the present fourth dose of
      inactivated polio vaccine given at 5 years of age and the diphtheria-tetanus
      toxoids given at 10 years of age with a combined diphtheria-tetanus-polio
      acellular pertussis vaccine dose to be given at 5-6 years of age. A fifth dose of
      a DTPaPolio vaccine should be considered at 15-18 years of age.

PMID- 11577640
TI  - [Vaccination offers good protection against measles, mumps and rubella. To refuse
      vaccination would seriously threaten our good immunity status].
AB  - Since vaccination against measles, rubella and mumps (MMR) was introduced in
      Sweden in 1982 for children at 1.5 and 12 years of age these diseases have almost
      completely disappeared. Severe side effects have been rare. Threats against the
      continued protection from these diseases include a lessening inclination on the
      part of parents to vaccinate their children, a weakening of the vaccine-induced
      immunological response with time, and possibly also genetic changes in strains of
      circulating wild type virus. By law physicians are bound to report diagnosed
      cases as well as new or severe side effects. Continuous laboratory analysis of
      antibodies and circulating viruses is also necessary.

PMID- 11577641
TI  - [Twin-twin transfusion syndrome--front line in fetal medicine].
AB  - Twin-twin transfusion develops in 10-20% of monochorionic twin pregnancies. As
      far as we know the underlying disturbance is an unbalanced anastomosis between
      the two fetuses on the placental surface. Without treatment mortality is as high
      as 80% if diagnosed before viability. One of this article's authors spent two
      months in Hamburg at the 'Allgemeine Krankenhaus', Barmbeck in Germany and
      describes the technique used there to coagulate these anastomoses via fetoscope.
      The outcome seems very promising with overall survival of 80% using this method.
      In the article pathogenesis and alternative treatments are also discussed.

PMID- 11577642
TI  - [Metabolic diseases in newborn infants--diagnosis and treatment].
AB  - Different symptoms and clinical signs of metabolic disease in the neonatal period
      are reviewed. Initial laboratory studies dealing with critically ill neonates are
      recommended. Different biochemical findings are commented and linked towards the
      most probable diseases. Finally, treatment in the acute phase of disease is
      presented.

PMID- 11577643
TI  - [Patients with frontal lobe dementia. A national center of knowledge works for
      better care].

PMID- 11577644
TI  - [Homocysteine--not a risk factor but a marker of deficiency and risk].

PMID- 11577645
TI  - [Phenotypic expression of a mutation in MEN 2A documented in a family in the
      western part of Sweden].
AB  - A missense mutation at codon 618 of the RET proto-oncogene is a rather unusual
      cause of multiple endocrine neoplasia 2A. We report the phenotypic expression of
      this specific RET mutation in a large Swedish family. The family was mapped back
      to the 18th century. Since 1971 the family has been included in a biochemical
      screening program, and since 1994 has undergone genetic screening. Twenty-seven
      individuals were found to have medullary thyroid carcinoma (MTC). Eighteen were
      detected by screening. The incidence of pheochromocytoma (4%) and
      hyperparathyroidism (7%) was low. Five individuals died of MTC, but of these none
      had been included in the screening program. One patient underwent prophylactic
      thyroidectomy after positive genetic screening. MTC tumor aggressivity differed
      markedly between gene carriers. The screening program shows that the clinical
      aggressivity of MTC can be mitigated by early and adequate surgical intervention.

PMID- 11577646
TI  - [Prehospital care soon to be routine in suspected acute coronary syndrome].
AB  - Among patients with a suspected acute coronary syndrome the early phase is
      particularly critical. At that stage, pain is most intense and the risk of life
      threatening arrhythmia is greatest. Also at that stage, the prospect of limiting
      infarct size and maybe even protecting patients from developing myocardial damage
      is at its best. Thrombolytic treatment initiated prior to hospital admission has
      been shown to more effectively reduce mortality in acute myocardial infarction
      than thrombolytic therapy initiated after admission. Swedish pre-hospital care
      appears to have adapted relatively well in this aspect of clinical care.

PMID- 11577647
TI  - [Modernization in China results in changed problems concerning disease
      protection].

PMID- 11577648
TI  - [Patient transportation by boat when the hospital in Skara was closed].

PMID- 11577649
TI  - [The law on compulsory notification concerning firearms is a legal and practical
      monstrosity].

PMID- 11577650
TI  - [Politicians should be more responsible when it comes to alternative medicine].

PMID- 11577651
TI  - [What is the future of general practice?].

PMID- 11577652
TI  - [Incomplete statement on inhalation aerosols].

PMID- 11577653
TI  - A transtheoretical approach to changing organizations.
AB  - Several authors have reflected on the underdeveloped state of organizational
      change theory, research, and practice. This field needs an integrative framework
      that can synthesize major approaches to change. The Transtheoretical Model has
      the potential to do for organizational change what it has done for individual
      behavior change. Conceptually the stages-of-change dimension can be used to
      integrate principles and processes of change from divergent models of change.
      Practically, the stages-of-change dimension can be applied by leaders to reduce
      resistance, increase participation, reduce dropout, and increase change progress
      among employees.

PMID- 11577654
TI  - Cost of treatment failure for major depression: direct costs of continued
      treatment.
AB  - Understanding subsequent costs of treating patients who fail initial treatment
      for depression is critical in cost-effectiveness analysis. This prospective
      observational study calculated such costs in a community mental health center.
      Total mean annual direct per-patient costs were $6,818 to $8,661. This total was
      markedly higher than those reported in studies that were based partially on the
      assumptions of expert panels rather than observed utilization rates. These
      results suggest that in settings similar to the present study, antidepressant
      treatments with higher failure rates may carry a marked hidden cost disadvantage.

PMID- 11577655
TI  - Work interest as a predictor of competitive employment: policy implications for
      psychiatric rehabilitation.
AB  - Consumers with serious mental illness (N = 166) enrolling in two community-based
      mental health programs, a vocational Program of Assertive Community Treatment and
      a clubhouse certified by the International Center for Clubhouse Development
      (ICCD), were asked about their interest in work. About one third of the new
      enrollees expressed no interest in working. Equivalent supported employment
      services were then offered to all participants in each program. Stated interest
      in work and receipt of vocational services were statistically significant
      predictors of whether a person would work and how long it would take to get a
      job. Two thirds of those interested in work and half of those with no initial
      interest obtained a competitive job if they received at least one hour of
      vocational service. Once employed, these two groups held comparable jobs for the
      same length of time. These findings demonstrate the importance of making
      vocational services continuously available to all people with serious mental
      illness, and the viability of integrating these services into routine mental
      health care.

PMID- 11577656
TI  - Cross-system service use among VA mental health patients living in Philadelphia.
AB  - There are few published studies of cross-system use of multiple systems of mental
      health care. This study examines use of VA and non-VA services in Philadelphia
      County. Results indicated that rates of cross-system use overall are fairly low
      (16 to 17% of patients across all years), are generally declining over time, and
      account for a small proportion of total all-system costs (4%). Veterans who used
      more VA inpatient services also used more non-VA services, and veterans who used
      fewer VA outpatient services used more non-VA services, indicating that cross
      system use may be a quality indicator for the accessibility or acceptability of
      outpatient care.

PMID- 11577657
TI  - Guidelines for studies that involve placebo controls: the Massachusetts approach.

PMID- 11577658
TI  - Have I got a worker for you: creating employment opportunities for people with
      psychiatric disability.

PMID- 11577659
TI  - World Health Organization and top publishers announce breakthrough on developing
      countries' access to leading biomedical journals.

PMID- 11577660
TI  - Developing a decision support system to meet nurse managers' information needs
      for effective resource management.
AB  - This article describes the development of a decision support system called
      CLASSICA, which assists nurse managers in financial management, resource
      allocation, activity planning, and quality control. CLASSICA integrates
      information about patient flow and activity, staffing, and the cost of nursing
      care at the nursing-unit level. The system provides assistance in planning
      activities, balancing the budget, and identifying barriers to unsatisfactory
      resource management. In addition, CLASSICA contains forecasting and simulation
      options to analyze the influence of factors that affect nursing costs. This
      article describes the system's development process steps to tailor it to the
      needs of nurse managers and their existing work practices. Nurse managers
      actively participated in defining their tasks and responsibilities; identified
      barriers and difficulties in managing these tasks; defined information needs,
      data input, and output and interface requirements; and identified expected
      benefits. Clear communication of project goals, strong user involvement, and
      purposeful benefit planning was used to achieve the goals for CLASSICA: (1) to
      provide essential information and decision support for effective financial
      management, resource allocation, activity planning, and staffing; (2) to improve
      nurse managers' competence in financial management and decision making; (3) to
      improve cost containment; and (4) to provide a helpful and easy to use tool for
      decision support.

PMID- 11577661
TI  - A computer expert system prototype for mechanically ventilated neonates
      development and impact on clinical judgment and information access capability of
      nurses.
AB  - A computer expert system is an alternative method of training and providing real
      time clinical decision support for nurses to advance their practices from a
      novice to a proficient level. The purpose of this study was twofold: (1) to
      develop a prototype of a computer expert system for mechanically ventilated
      neonates (ES-MVN) and (2) to assess the impact of the ES-MVN on the clinical
      judgment and information access capability of nurses. Five steps used in
      developing the prototype are described in this article. The ES-MVN is a
      multimedia interactive consultation-based program that contains 2 major parts:
      the nursing diagnosis and the knowledge base on nursing care of mechanically
      ventilated neonates. A rule-based (Boolean frame) was chosen for the nursing
      diagnosis decision model. The prototype was developed on the Web server and a
      combination of computer applications operated in a Microsoft Windows environment.
      A quasi-experimental, 1-group pretest-posttest design was used to measure the
      efficacy of the ES-MVN in 16 neonatal intensive care unit registered nurses. Case
      simulations were used to test the nurses' clinical judgment performance. The
      results showed a significant increase in the nurses' performance scores of
      diagnoses and managed care after using the ES-MVN (t[15] = 17.21, P = .0001). The
      nurses' scores for perceptions of their information access capability and
      clinical judgment ability after receiving the ES-MVN were significantly higher
      than before installing the ES-MVN in the neonatal intensive care unit (ts[15] =
      6.91 and = 17.53, Ps = .0001, respectively). The findings suggest the usefulness
      of the computer expert system as an effective tool to support nurses' clinical
      judgment in critical care situations and to provide access to information at the
      practice site.

PMID- 11577662
TI  - Piloting use of computerized practice tests.
AB  - This study piloted the use of computerized practice tests in an undergraduate
      nursing pathopharmacology course and collected questionnaire data on the
      students' experiences. Two computer-administered practice tests were available to
      help students prepare for the course's paper-and-pencil unit examinations. The
      software testing package, LXR-Test 5.1, was used to generate the practice tests.
      Twenty-eight students took one or both computer practice tests. Group mean course
      examination scores were higher for subjects taking the computer practice tests
      compared with subjects who did not take the computer practice tests, but these
      scores were not found to be significantly different (P = 0.29; P = 0.07). Final
      questionnaire results showed students enjoyed taking the computerized practice
      tests to prepare for course examinations and liked the immediate scoring and test
      summary printouts. After this experience, students felt more prepared to take the
      computerized licensure examination. Did students feel ready to take required
      course examinations via computer in future courses? Responses were mixed.

PMID- 11577663
TI  - Deep versus surface learning with multimedia in nursing education development and
      evaluation of WoundCare.
AB  - Examination of the software design-learning relationship is mandatory if
      significant benefits are to be derived from the development and use of
      Interactive multimedia in nursing education. This article reports on the
      development and student evaluation of WoundCare: An Interactive Learning Program
      for Health Professionals (version 1.0a). Of particular interest to those involved
      in nursing education is the extent to which the learning activities incorporated
      in WoundCare promote "deep" rather than "surface" learning. Specific design
      features believed to facilitate and inhibit deep learning are identified.
      Modifications that could increase the learning effectiveness of WoundCare and
      other interactive multimedia programs are proposed.

PMID- 11577664
TI  - The cost of the amalgam issue.

PMID- 11577665
TI  - National campaign will promote oral cancer awareness.

PMID- 11577666
TI  - Oral cancer is dentistry's disease, but we are losing the battle.

PMID- 11577667
TI  - The best cosmetic service our profession can provide.

PMID- 11577668
TI  - Oral cancer in the molecular age.
AB  - Oral cancer represents an accumulation of defects in the genes that encode key
      proteins associated with growth and development. Dysregulation of these proteins
      is central to malignant conversion. This appears to involve three major changes
      in cell function: 1. altered cell growth, death and longevity; 2. unencumbered
      cell movement; and 3. development of a new blood supply (angiogenesis). Specific
      genes, such as p53, p27, p16, and cyclin D-1, are altered in oral cancer through
      mutation, amplification, or deactivation. These genes are also frequently altered
      in many other malignancies. In oral mucosa, etiologic agents--especially tobacco
      and alcohol, and possibly some viruses--are known to induce alterations in the
      genes and gene functions associated with cell cycle regulation, contributing to
      the development of squamous cell carcinoma and epithelial dysplasias.
      Identification of the specific genes/proteins and the sequence in which they
      appear in the transformation of a normal cell to a malignant cell is necessary
      for the formulation of new treatment strategies, the development of early
      detection methods, and the prediction of patient outcome.

PMID- 11577669
TI  - Soft-tissue examination in the dental office.
AB  - This article describes in detail all features of the head and neck soft-tissue
      examination as performed routinely in a dental office. The ongoing thought
      process while performing the exam is described, and examples of findings are
      given.

PMID- 11577670
TI  - Premalignant oral mucosal diseases.
AB  - A premalignant phase in the development of oral cancer is predicted by the
      classic model of experimental epithelial carcinogenesis. Virtually all oral
      squamous cell carcinomas arise from a premalignant precursor, but it is difficult
      to specifically define the term premalignant. Oral pathologists use the term
      epithelial dysplasia to indicate microscopic features in a biopsy specimen that
      are associated with a risk of malignant change and then assign a grade of
      severity. There is good correlation between higher grades of dysplasia and
      increasing risk of cancer but less so with the lower grades. The clinical
      appearances manifested by oral epithelial dysplasia and early oral cancer include
      leukoplakia, erythroplakia, and speckled leukoplakia. This paper discusses and
      illustrates these clinical lesions, their associated risk factors, their
      relationship to epithelial dysplasia, and the associated risk of evolution into
      oral cancer.

PMID- 11577671
TI  - Diagnosis and management of oral soft-tissue lesions: the use of biopsy,
      toluidine blue staining, and brush biopsy.
AB  - Upon discovery of a lesion after thorough oral soft-tissue examination, the
      dentist is confronted with the often-troublesome decision of how best to manage
      the patient. The management protocol must provide for early diagnosis in the case
      of oral cancer so as to reduce cancer morbidity and mortality. Options for
      management would include an observation period of some defined time, use of
      toluidine blue stain or oral brush biopsy to screen the lesion, or immediate
      biopsy and follow-up. This article reviews the assets and limitations of each and
      suggests a rational, science-based approach to diagnosis and management.

PMID- 11577672
TI  - Oral cancer: a self-assessment quiz.
AB  - This article consists of a quiz on oral cancer knowledge. The goals of the quiz
      are to reinforce known cancer information and present new information.
      Photographs are used to bring a sense of the practical problems that clinical
      pathology presents. Also, a number of real-life case situations are presented
      with their corresponding illustrations so that the readers may use their clinical
      judgment and experience in choosing an answer.

PMID- 11577673
TI  - Oral management of the patient with cancer in the head and neck region.
AB  - Cancer therapies--including surgery, radiation, and chemotherapy--may unfavorably
      affect the oral/dental health of patients. Existing dental problems can also
      result in serious complications that may be prevented by dental intervention
      prior to cancer therapy. This paper will be limited to a discussion of the
      detrimental effects of radiation therapy on the oral cavity and salivary glands
      and appropriate dental management.

PMID- 11577674
TI  - Satisfaction with HMO coverage: an empirical study of a medical school's faculty,
      staff, and administrators.

PMID- 11577675
TI  - A sociotechnical approach to patient safety: quality improvement in hospital
      laboratories.

PMID- 11577676
TI  - Automation of pharmacy systems: experiences and strategies of a rural healthcare
      system.

PMID- 11577677
TI  - Credentialing: the special problem of locum tenens physicians.

PMID- 11577678
TI  - Successful collaboration between hospitals and physicians: process or structure?

PMID- 11577680
TI  - Proceedings of the International Symposium: Autoimmunity Induced by Infection or
      Immunization. Annecy, France, 28 November-1 December 2000.

PMID- 11577679
TI  - Micronutrients and infection.

PMID- 11577682
TI  - [Proceedings of the 7th International Symposium of the Reina Sofia Institute of
      Nephrology Research. Madrid, Spain, 16-17 November 2000].

PMID- 11577681
TI  - Forensic pretrial police interviews of deaf suspects avoiding legal pitfalls.

PMID- 11577683
TI  - Abstracts of the 4th International Symposium on Bi-Digital O-Ring Test. Tokyo,
      Japan, July 21-23, 2000.

PMID- 11577684
TI  - Rapid wound healing: a multidimensional perspective.

PMID- 11577685
TI  - Proceedings of the 3rd Nestle Nutrition Conference. Nutrition and Brain Function
      from Infancy to Old Age. Mexico City, Mexico, March 30-31, 2000.

PMID- 11577686
TI  - ECG of the month: Wolff-Parkinson-White arrhythmias.

PMID- 11577687
TI  - A normalized plot as a novel and time-saving tool in complex enzyme kinetic
      analysis.
AB  - A new data treatment is described for designing kinetic experiments and analysing
      kinetic results for multi-substrate enzymes. Normalized velocities are plotted
      against normalized substrate concentrations. Data are grouped into n + 1 families
      across the range of substrate or product tested, n being the number of substrates
      plus products assayed. It has the following advantages over traditional methods:
      (1) it reduces to less than a half the amount of data necessary for a proper
      description of the system; (2) it introduces a self-consistency checking
      parameter that ensures the 'scientific reliability' of the mathematical output;
      (3) it eliminates the need for a prior knowledge of Vmax; (4) the normalization
      of data allows the use of robust and fuzzy methods suitable for managing really
      'noisy' data; (5) it is appropriate for analysing complex systems, as the
      complete general equation is used, and the actual influence of effectors can be
      typified; (6) it is amenable to being implemented as a software that incorporates
      testing and electing among rival kinetic models.

PMID- 11577688
TI  - Kinetic properties of the acylneuraminate cytidylyltransferase from Pasteurella
      haemolytica A2.
AB  - Neuroinvasive and septicaemia-causing pathogens often display a polysialic acid
      capsule that is involved in invasive behaviour. N-Acetylneuraminic acid (NeuAc)
      is the basic monomer of polysialic acid. The activated form, CMP-Neu5Ac, is
      synthesized by the acylneuraminate cytidylyltransferase (ACT; EC 2.7.7.43). We
      have purified this enzyme from Pasteurella haemolytica A2 to apparent homogeneity
      (522-fold). The protein behaved homogeneously on SDS/PAGE as a 43 kDa band, a
      size similar to that of Escherichia coli, calf, mouse and rat. Specific activity
      in crude lysate displayed one of the highest values cited in the literature (153
      m-units/mg). We have studied the steady-state kinetic mechanism of the enzyme by
      using normalized plot premises. The catalysis proceeds through a Ping Pong Bi Bi
      mechanism, with CTP as the first substrate and CMP-NeuAc as the last product. The
      true Km values were 1.77 mM for CTP and 1.82 mM for NeuAc. The nucleotides CDP,
      UTP, UDP and TTP, and the modified sialic acid N-glycolylneuraminic acid were
      also substrates of the ACT activity. The enzyme is inhibited by cytidine
      nucleotides through binding to a second cytidyl-binding site. This inhibition is
      greater with nucleotides that display a long phosphate tail, and the genuine
      inhibitor is the substrate CTP. At physiological concentrations, ATP is an
      activator, and AMP an inhibitor, of the ACT activity. The activated sugar UDP-N
      acetylglucosamine acts as an inhibitor, thus suggesting cross-regulation of the
      peptidoglycan and polysialic acid pathways. Our findings provide new mechanistic
      insights into the nature of sialic acid activation and suggest new targets for
      the approach to the pathogenesis of encapsulated bacteria.

PMID- 11577690
TI  - Australia: lawyers ponder tobacco firms' criminal liability.

PMID- 11577689
TI  - Sd(a)-antigen-like structures carried on core 3 are prominent features of glycans
      from the mucin of normal human descending colon.
AB  - This paper describes structural characterization by NMR, MS and degradative
      studies of mucin glycans from normal human descending colon obtained freshly at
      autopsy. The saccharides were mainly based on core 3 (GlcNAcbeta1-3GalNAc). Among
      the terminal saccharide determinants Sd(a)/Cad-antigen-like structures were
      prominent, and Lewis x, sialyl Lewis x and sulphated Lewis x were found as minor
      components, whereas blood group H and A antigenic determinants were absent. The
      saccharides were markedly different from those of mucins from colon cancers or
      colon cancer cell lines analysed so far, in which cores 1 and 2 are prominent
      features, and in which various other terminal determinants have been found, but
      not Sd(a)/Cad.

PMID- 11577691
TI  - Japan: can local action do the trick?

PMID- 11577692
TI  - UK: university's tobacco stain won't go away.

PMID- 11577693
TI  - Kenya: smoke, and be your own boss.

PMID- 11577694
TI  - Turkey: the trade-health divide.

PMID- 11577695
TI  - Developing countries take the lead on WHO convention.

PMID- 11577696
TI  - [Freedom and accountability in modern medicine].

PMID- 11577698
TI  - [Everything fine? For progress within human capacity].

PMID- 11577697
TI  - [Speech of Ulla Schmidt, National Minister of Health Care, Germany].

PMID- 11577699
TI  - [Patients desire a direct access to medical specialists].

PMID- 11577700
TI  - Effect of preproTRH antisense on thyrotropin-releasing hormone synthesis and
      viability of cultured rat diencephalic neurons.
AB  - To investigate a possible neurotropic role for thyrotropin-releasing hormone
      (TRH) in the central nervous system, we used recombinant antisense TRH adenovirus
      (TRHav) to "knock out" TRH in cultured 17-d fetal rat diencephalon. The
      morphology along with beta-galactosidase (beta-gal) enzyme histochemistry (X-gal
      staining) and TRH content (femtomoles/well) were used to measure the effect of
      antisense TRH virus. Control adenovirus mediated beta-gal transfection efficiency
      was nearly 85%, as shown by positive X-gal staining, and was without effect on
      cell morphology, TRH content, or the normal response to glucocorticoid
      (dexamethasone) exposure with enhanced TRH expression. A significant 90% decline
      in TRH content as well as changes in neuronal morphology (shrunken cell bodies
      and short dendrites) were observed after 14 but not 7 d following TRHav
      treatment. The addition of synthetic TRH peptide at 2.5 microM along with TRHav,
      but not dexamethasone, partly prevented the morphologic changes. No morphologic
      changes were seen in wild-type AtT20 cells, a pituitary cell line that does not
      produce TRH. To investigate whether neuronal death from loss of proTRH was owing
      to apoptosis, neuronal DNA change by means of fluorescent dye H-33342 staining,
      TUNEL staining, and DNA laddering analysis was examined. Eighty to 90% positive H
      33342 and TUNEL staining as well as a 180- to 200-bp DNA fragment on DNA
      laddering analysis were found as compared to control. These results indicate that
      proTRH gene expression prevents neuronal apoptosis and may play a role in
      neuronal development and function.

PMID- 11577701
TI  - [WKW online--a further step in internationalization of the Wiener klinische
      Wochenshrift].

PMID- 11577702
TI  - Toxins as weapons of mass destruction. A comparison and contrast with biological
      warfare and chemical-warfare agents.
AB  - Toxins are toxic chemical compounds synthesized in nature by living organisms.
      Classifiable by molecular weight, source, preferred targets in the body, and
      mechanism of action, they include the most potent poisons on the planet, although
      considerations of production, weaponization, delivery, environmental stability,
      and host factors place practical limits on their use as WMD. The two most
      important toxin threats on the battlefield or in bioterrorism are probably
      botulinum toxin (a series of seven serotypes, of which botulinum toxin A is the
      most toxic for humans) and SEB, an incapacitating toxin. Ricin and the
      trichothecene mycotoxins, including T-2 mycotoxin, are of lesser concern but are
      still potential threats. Botulinum toxin is a neurotoxin, ricin and trichothecene
      mycotoxins are membrane-damaging proteins, and SEB is a superantigen capable of
      massive nonspecific activation of the immune system. The clinical intoxications
      resulting from exposure to and absorption (usually by inhalation) of these agents
      reflect their underlying pathophysiology. Because of the hybrid nature of toxins,
      they have sometimes been considered CW agents and sometimes BW agents. The
      current trend seems to be to emphasize their similarities to living organisms and
      their differences from CW agents, but examination of all three groups relative to
      a number of factors reveals both similarities and differences between toxins and
      each of the other two categories of non-nuclear unconventional WMD. The
      perspective that groups toxins with BW agents is logical and very useful for
      research and development and for administrative and treaty applications, but for
      medical education and casualty assessment, there are real advantages in clinician
      use of assessment techniques that emphasize the physicochemical behavior of these
      nonliving, nonreplicating, intransmissible chemical poisons.

PMID- 11577703
TI  - Reentry in a morphologically realistic atrial model.
AB  - INTRODUCTION: Atrial fibrillation is the most common cardiac arrhythmia. In
      ablation procedures, identification of the reentrant pathways is vital. This has
      proven difficult because of the complex morphology of the atria. The purpose of
      this study was to ascertain the role of specific anatomic structures on reentry
      induction and maintenance. METHOD AND RESULTS: A computationally efficient,
      morphologically realistic, computer model of the atria was developed that
      incorporates its major structural features, including discrete electrical
      connections between the right and left atria, physiologic fiber orientation in
      three dimensions, muscle structures representing the crista terminalis (CT) and
      pectinate muscles, and openings for the veins and AV valves. Reentries were
      induced near the venous openings in the left and right atria, the mouth of the
      coronary sinus, and the free wall of the right atrium. The roles of certain
      muscular structures were ascertained by selectively removing the structures and
      observing how the propagation of activity was affected. CONCLUSION: (1) The
      muscular sheath of the coronary sinus acts as a pathway for a reentrant circuit
      and stabilizes any circuits that utilize the isthmus near the inferior vena cava.
      (2) Poor trans-CT coupling serves to stabilize flutter circuits. (3) Wall
      thickness is an important factor in the propagation of electrical activity,
      especially in the left atrium. (4) The openings of the inferior and superior
      venae cavae form natural anatomic anchors that make reentry easier to initiate by
      allowing for smaller ectopic beats to induce reentry.

PMID- 11577704
TI  - Hyperprocessing reaction of tRNA by Bacillus subtilis ribonuclease P ribozyme.

PMID- 11577705
TI  - Low-density lipoprotein induced actin cytoskeleton reorganization in endothelial
      cells: mechanisms of action.
AB  - The inhibitory effects of the specific NADPH oxidase inhibitor, apocynin, and non
      specific NADPH oxidase inhibitors, nordihydroguaiaretic acid (NDGA) and SKF525A,
      on the disruption of dense peripheral bands and formation of stress fibers in
      cultured human umbilical vein endothelial cells exposed to atherogenic low
      density lipoprotein (LDL) levels has been investigated. Endothelial cells (EC) in
      vitro and in vivo exposed to high LDL-cholesterol levels have cytoskeletal
      remodeling with stress fiber formation and loss of dense peripheral bands.
      Cultured EC incubated with exogenously applied hydrogen peroxide (H2O2: 1 mM)
      have cytoskeletal structural changes much similar to those observed with high LDL
      exposure. Previous studies have 1) demonstrated that exposure to atherogenic LDL
      levels causes heightened EC H2O2 production, 2) identified the reactive oxygen
      species source, NADPH oxidase, in EC, and 3) shown that the specific NADPH
      oxidase inhibitor, apocynin, and non-specific NADPH oxidase inhibitors, NDGA and
      SKF525A, suppress H2O2 production increases in high LDL-perturbed EC. In the
      present study, the cytoskeletal structure of EC exposed to 330 mg/dl LDL
      cholesterol, and incubated with or without apocynin, NDGA and SKF525A, was
      examined. Each of these compounds promoted the retention of dense peripheral
      bands and minimized stress fiber formation. These findings are consistent with
      NADPH oxidase and it's reactive oxygen species byproducts modulating the
      cytoskeleton reorganization observed in high LDL-induced EC perturbation.

PMID- 11577706
TI  - Spin-trapping study on the hydroxyl radical formed from a tea catechin-Cu(II)
      system.
AB  - A spin-trapping method was applied to examine the formation of the hydroxyl (OH)
      radical from a tea catechin-Cu(II) system to elucidate a previous result that
      some tea catechin-Cu(II) systems induced DNA scission. Three tea catechins, (-)
      epigallocatechin (EGC), (-)-epigallocatechin gallate (EGCg) and (-)-epicatechin
      (EC), were used. The spin-trapping agent, 5,5'-dimethyl-pyrroline-1-oxide (DMPO),
      was dissolved in a pH 9 phosphate buffer solution, then a catechin and Cu(II)
      were added in that order, and the ESR spectral change was monitored for one hour.
      The order of adding the catechin and Cu(II) was then reversed, and the ESR
      spectral change was again monitored to examine the coordinating activity of each
      catechin toward the Cu(II) ion and the effect on OH radical generation. The
      intensity changes of the spin adducts, DMPO-OH, DMPO-CH3 and DMPO-H, were
      analyzed, the results suggesting that the OH radical generated in the system
      decomposed DMPO, resulting in the formation of DMPO-CH3 and DMPO-H. The results
      show that EGC formed a stable complex with Cu(II) and generated the OH radical.
      EGCg seemed to have this activity, but the OH radical that was generated was
      scavenged by the gallate group existing in the complex. EC did not show strong
      coordinating and OH-generating activities. These characteristics of the three
      catechins are consistent with the results shown for DNA scission.

PMID- 11577707
TI  - Identification of 3,4-dihydroxy-2-oxo-butanal (L-threosone) as an intermediate
      compound in oxidative degradation of dehydro-L-ascorbic acid and 2,3-diketo-L
      gulonic acid in a deuterium oxide phosphate buffer.
AB  - Dehydro-L-ascorbic acid (DAA), an oxidation product of L-ascorbic acid (vitamin
      C), is unstable in the neutral and basic pH regions. When DAA was incubated in a
      phosphate buffer with deuterium oxide (pH 7.4), it was degraded to form the main
      degradation compound, which was identified as 3,4-dihydroxy-2-oxobutanal (L
      threosone). This compound was also formed from diketo-L-gulonic acid (DKG) in a
      phosphate buffer with deuterium oxide. L-threosone had reducing activity,
      probably due to its enolization, and is likely to have been involved in the
      formation of the reducing activity that was observed in aqueous DAA and DKG
      solutions. As a reactive dicarbonyl compound, L-threosone might also take some
      role in the cross-linking of tissue proteins that are formed in vivo in the
      Maillard reaction.

PMID- 11577708
TI  - Influence of alpha-helices on the emulsifying properties of proteins.
AB  - A peptide derived from apomyoglobin by cyanogen bromide cleavage was found to be
      an active emulsifier. This molecule, peptide 1-55, has two potential amphipathic
      alpha-helices and a hydrophilic C-terminal domain. The importance of each of
      these domains to the emulsifying properties of this molecule was investigated by
      testing the products of gene constructs based on the sequence of peptide 1-55,
      but lacking one of the three domains. The emulsifying activity of the peptides
      lacking either of the alpha-helices was correlated with the hydrophobic moments
      of their respective helices. The hydrophobic moment is a measure of the
      amphipathicity of alpha-helices; a hydrophobic moment analysis of other
      emulsifying peptides supports the hypothesis that a high hydrophobic moment
      contributes to good emulsifying properties in a molecule which contains alpha
      helices.

PMID- 11577709
TI  - Aggregation pheromone activity of the female sex pheromone, beta-acaridial, in
      Caloglyphus polyphyllae (Acari: Acaridae).
AB  - Caloglyphus (= Sancasania) polyphyllae discharges from a pair of opisthonotal
      glands a characteristic set of volatiles, i.e. three monoterpenes and seven
      hydrocarbons. Among them, beta-acaridial, which is known as the female sex
      pheromone of the species and has antifungal activity, was newly identified as the
      aggregation pheromone for unfeeding and unmating mites. Feeding mites, however,
      exhibited sexually aroused behavior instead of the tendency to cluster when
      exposed to beta-acaridial. This is the first example of the compound
      demonstrating two pheromone functions depending upon the circumstances faced by
      the mites.

PMID- 11577710
TI  - Consumption of hypoallergenic flour prevents gluten-induced airway inflammation
      in Brown Norway rats.
AB  - Brown Norway rats were immunized with gluten, and then fed a diet containing
      hypoallergenic flour or an amino acid mixture. The rats were then made to inhale
      a solubilized gluten to induce gluten-specific bronchial asthma. The antibody
      levels in the serum of rats were measured by ELISA, and cell counts were done on
      cytospin preparations of bronchoalveolar lavage fluid. Body weight was decreased
      after allergen challenge in rats fed the amino acid mixture but not in rats fed
      the hypoallergenic flour. Antibody levels in the serum were significantly lower
      in rats fed hypoallergenic flour than in those fed the amino acid mixture.
      Differential cell counts in the bronchoalveolar lavage fluid showed that the
      numbers of eosinophils, lymphocytes, and neutrophils were significantly lower in
      rats fed the hypoallergenic flour than in those fed the amino acid mixture. These
      results suggest that hypoallergenic flour actively suppresses the allergic
      reactions, probably by inducing oral tolerance.

PMID- 11577711
TI  - Novel method for enzymatic synthesis of CMP-NeuAc.
AB  - A novel method for synthesizing CMP-NeuAc was established. We first confirmed
      that the putative neuA gene of Haemophilus influenzae, identified by its whole
      genome sequence project, indeed encodes CMP-NeuAc synthetase (EC 2.7.7.43). The
      enzyme requires CTP as a cytidylyl donor for cytidylylation of NeuAc. The enzyme
      was coupled with an enzymatic CTP-generating system from CMP and inorganic
      polyphosphate as a sole phospho-donor driven by the combination of polyphosphate
      kinase and CMP kinase, where phosphorylation of CMP is done by the combined
      activity expressed by both enzymes, and subsequent phosphorylation of CDP by
      polyphosphate kinase itself occurred efficiently. When CMP-NeuAc synthetase of H.
      influenzae, polyphosphate kinase, and CMP kinase were added to the reaction
      mixture containing equimolar concentrations (15 mM) of CMP and NeuAc, and
      polyphosphate (150 mM in terms of phosphate), CMP-NeuAc was synthesized up to 10
      mM in 67% yield.

PMID- 11577712
TI  - Apoptosis induction by T-2 toxin: activation of caspase-9, caspase-3, and DFF
      40/CAD through cytosolic release of cytochrome c in HL-60 cells.
AB  - The molecules participating in apoptosis induced by T-2 toxin in human leukemia
      HL-60 cells were investigated. The rank order of the potency of trichothecene
      mycotoxins to induce internucleosomal DNA fragmentation was found to be T-2,
      satratoxin G, roridin A >> diacetoxyscirpenol > baccharin B-5 >> nivalenol,
      deoxynivalenol, 3-acetyldeoxynivalenol, fusarenon-X, baccharin B-4=vehicle
      control. Western blot analysis of caspase-3 in T-2-treated cells clearly
      indicated the appearance of its catalytically active fragment of 17-kDa.
      Increased caspase-3 activity was also detected by using a fluorogenic substrate,
      DEVD-AMC. Next, cells exposed to T-2 led to cleavage of PARP from its native 116
      kDa form to the 85-kDa product. Moreover, DFF-45/ICAD were cleaved to give a 12.5
      kDa fragment via T-2 treatment. T-2 caused the release of cytochrome c from
      mitochondria into the cytosol. Increased enzymic activity of caspase-9 on LEHD
      AMC was shown. These data indicate that T-2-induced apoptosis involves activation
      of caspase-3 and DFF-40/CAD through cytosolic accumulation of cytochrome c along
      with caspase-9 activation.

PMID- 11577713
TI  - Comparative effects of dietary fat types on hepatic enzyme activities related to
      the synthesis and oxidation of fatty acid and to lipogenesis in rats.
AB  - The effects of different types of dietary fat on the activities of hepatic
      enzymes related to fatty acid synthesis [glucose-6-phosphate dehydrogenase
      (G6PDH) and acetyl-CoA carboxylase (ACC)], oxidation [acyl-CoA synthetase (AST),
      carnitine palmitoyl transferase (CPT), and peroxisomal beta-oxidation (PbetaOX)],
      and lipogenesis [phosphatidate phosphohydrolase (PAP), diacylglycerol
      acyltransferase (DGAT), and phosphocholine diacylglycerol transferase (PCDGT)],
      and plasma and liver lipid levels were investigated in male Wistar rats. The
      animals were 6 weeks old and about 120 g of body weight, and were fed on test
      diets containing 20% of a mixture of tripalmitin, tristearin and corn oil (SFA),
      olive oil (OLI), sunflower oil (SUN), linseed oil (LIS), and sardine oil (SAR)
      for 2 weeks. The concentrations of plasma total cholesterol (T-CHOL), high
      density lipoprotein-cholesterol (HDL-CHOL), triacylglycerol (TG) and phospholipid
      (PL) were generally higher in the rats fed on SFA and OLI than in those given
      SUN, LIS and SAR. The rats fed on OLI had a higher level of liver T-CHOL than
      those fed on the other fats. The liver TG content was nearly higher from the
      intake of SFA and OLI than from SUN, LIS and SAR, although the liver PL level was
      not affected by the type of dietary fat. The SFA and OLI groups had the highest
      activities of hepatic G6PDH and ACC, and the SAR group, the lowest activities.
      The activities of AST and CPT, and peroxisomal PbetaOX in the liver were higher
      in the rats fed on the LIS and SAR diets than in those given the other diets. The
      hepatic PAP activity was higher from the intake of OLI and SUN, and tended to be
      higher from SFA than from LIS and SAR. The activity of liver DGAT was higher from
      SFA and inclined to be higher from OLI, SUN, and LIS than from SAR, while the
      PCDGT activity in the liver was not effected by the type of dietary fat. The
      concentrations of plasma and liver TG were generally positively correlated with
      the activities of liver enzymes related to the synthesis of fatty acids and
      lipids, and negatively with those involved in fatty acid oxidation. Based on
      these results, it is suggested that the levels of plasma and liver TG were
      controlled by different types of dietary fat through changes in the hepatic
      enzyme activities related to fatty acid synthesis, lipogenesis, and fatty acid
      oxidation.

PMID- 11577714
TI  - The third naturally occurring attractant toward zoospores of phytopathogenic
      Aphanomyces cochlioides from the Spinacia oleracea host plant.
AB  - A bioassay-guided survey of spinach leaf constituents resulted in 5,4'-dihydroxy
      3,3'-dimethoxy-6,7-methylenedioxyflavone being identified as the third naturally
      occurring attractant in the host plant toward the zoospores of its pathogen,
      Aphanomyces cochlioides. The isolate showed attracting activity around Chromosorb
      W AW particles (60-80 mesh) coated with a 10(-5) M solution in a zoospore
      suspension. However, this activity was 1/100-1/1000 less than that of
      cochliophilin A, an attractant in the roots of spinach. Bioassays with the
      present isolate and related compounds revealed that 5,3',4'-trihydroxy-3-methoxy
      6,7-methylenedioxyflavone did not possess attractant activity, but rather weak
      antagonistic activity toward the former two attractants from spinach.

PMID- 11577715
TI  - Effects of amino acids on the amidation of polyaromatic carboxylic acids by
      Bacillus cereus.
AB  - The soil bacterium Bacillus cereus Tim-r01 efficiently transformed polyaromatic
      carboxylic acids (PACA) such as 4-biphenylcarboxylic acid (4-BPCA), 4
      biphenylacetic acid, and 4-phenoxybenzoic acid into their corresponding amides.
      The amidation activity was expressed at 37 degrees C (pH 7-8) in the presence of
      grown cells in nutrients under an aerobic atmosphere. Other strains of B. cereus,
      IFO 3001 and IAM 1229, also gave the amide from 4-BPCA. In phosphate-buffered
      saline (PBS), the addition of normal amino acids was essential, while sulfur
      containing amino acids such as methionine and cysteine drastically inhibited the
      amidation. Tracer experiments using N-15-isoleucine and N-15-alanine showed that
      the nitrogen atom of the amide came from an amino group of amino acids but not
      from ammonia or alkylamines.

PMID- 11577716
TI  - Binding of a highly de-N-acetylated chitosan to Japanese pheasan lysozyme as
      measured by 1H-NMR spectroscopy.
AB  - Binding of a highly de-N-acetylated chitosan to Japanese pheasant lysozyme (JPL),
      which differs from hen egg white lysozyme (HEWL) by nine amino acid substitutions
      (including Arg114-->His), was investigated by 1H-NMR spectroscopy. The profile of
      the one-dimensional spectrum of JPL is essentially identical to that of HEWL.
      Using two-dimensional spectra of JPL and HEWL, several aromatic and aliphatic
      proton resonances of JPL were assigned by comparison. When a highly de-N
      acetylated chitosan (number-average degree of polymerization, about 18; degree of
      acetylation, 0.04), where the N-acetylated units are predominantly surrounded by
      de-N-acetylated units (a monoacetylated chitosan), was added to the JPL solution,
      the NMR signals were clearly affected in Trp28 C5H and Ile98 gammaCH, as in the
      case of binding to HEWL. The dissociation constant of the monoacetylated chitosan
      evaluated from the NMR signal responses was calculated to be 0.23+/-0.05 mm (
      31.5 kJ/mol), which is similar to that of HEWL (0.11+/-0.02 mm, -33.3 kJ/mol).
      Thus, the Arg-->His substitution of the 114th amino acid, which participates in
      sugar residue binding at the right-sided subsite F, did not significantly affect
      the chitosan binding. In addition, the C2H signal of His114 of JPL was not
      affected by the chitosan binding. These results suggest that the monoacetylated
      chitosan binds to subsites E and F through the left-sided binding mode.

PMID- 11577717
TI  - Biotransformation of phenanthrene and 1-methoxynaphthalene with Streptomyces
      lividans cells expressing a marine bacterial phenanthrene dioxygenase gene
      cluster.
AB  - The phdABCD gene cluster in a marine bacterium Nocardioides sp. strain KP7 codes
      for the multicomponent enzyme phenanthrene dioxygenase. phdA encoding an iron
      sulfur protein large subunit alpha, phdB encoding its small subunit beta, phdC
      encoding ferredoxin, and phdD encoding ferredoxin reductase, were replaced in
      such a way that the termination codons of the preceding open reading frames were
      overlapped with the initiation codons of the following genes. This manipulated
      phdABCD gene cluster was positioned downstream of the thiostrepton-inducible
      promoter PtipA in a high-copy-number vector pIJ6021, and introduced into the gram
      positive, soil-inhabiting, filamentous bacterium Streptomyces lividans. The
      recombinant S. lividans cells converted phenanthrene into a cis-diol form, which
      was determined to be cis-3,4-dihydroxy-3,4-dihydrophenanthrene by its UV spectral
      data as well as HPLC property, using the authentic sample for comparison. This
      biotransformation proceeded very efficiently; 200 microM and 2 mm of phenanthrene
      were almost completely converted to its cis-diol form in 6 h and 32 h,
      respectively. In addition, the S. lividans cells carrying the phdABCD gene
      cluster were found to transform 1-methoxynaphthalene to two products, which were
      identified to be 8-methoxy-2-naphthol in addition to 8-methoxy-1,2-dihydro-1,2
      naphthalenediol by their EI-MS, 1H- and 13C-NMR spectral data.

PMID- 11577718
TI  - Comparison of the omega-transaminases from different microorganisms and
      application to production of chiral amines.
AB  - Microorganisms that are capable of (S)-enantioselective transamination of chiral
      amines were isolated from soil samples by selective enrichment using (S)-alpha
      methyl-benzylamine ((S)-alpha-MBA) as a sole nitrogen source. Among them,
      Klebsiella pneumoniae JS2F, Bacillus thuringiensis JS64, and Vibrio fluvialis
      JS17 showed good omega-transaminase (omega-TA) activities and the properties of
      the omega-TAs were investigated. The induction level of the enzyme was strongly
      dependent on the nitrogen source for the strains, except for V. fluvialis JS17.
      All the omega-TAs showed high enantioselectivity (E>50) toward (S)-alpha-MBA and
      broad amino donor specificities for arylic and aliphatic chiral amines. Besides
      pyruvate, aldehydes such as propionaldehyde and butyraldehyde showed good amino
      acceptor reactivities. All the omega-TAs showed substrate inhibition by (S)-alpha
      MBA above 200 mm. Moreover, substrate inhibition by pyruvate above 10 mm was
      observed for omega-TA from V. fluvialis JS17. In the case of product inhibition,
      acetophenone showed much greater inhibitions than L-alanine for all omega-TAs.
      Comparison of the enzyme properties indicates that omega-transaminase from V.
      fluvialis JS17 is the best one for both kinetic resolution and asymmetric
      synthesis to produce enantiomerically pure chiral amines. Kinetic resolution of
      sec-butylamine (20 mM) was done under reduced pressure (150 Torr) to selectively
      remove an inhibitory product (2-butanone) using the enzyme from V. fluvialis
      JS17. Enantiomeric excess of (R)-sec-butylamine reached 94.7% after 12 h of
      reaction.

PMID- 11577719
TI  - Production of pyridoxal phosphate by a mutant strain of Schizosaccharomyces
      pombe.
AB  - Conditions for extracellular production of vitamin B6 compounds (B6), especially
      pyridoxal 5'-phosphate (PLP) by Schizosaccharomyces pombe leul strain were
      examined. The productivity was dependent on concentration of L-leucine in the
      culture medium: 30 mg/l gave the highest concentrations of total B6 and PLP. The
      viable cells harvested at different growth phases showed different productivity:
      middle and late exponential phase cells showed the highest productivity of total
      B6 and PLP, respectively. D-Glucose (1%, w/v) among other sugars gave the best
      productivity. Supplementation of air and ammonium sulfate significantly increased
      extracellular production of PLP. Superoxide anion producers, menadione and
      plumbagin, and H202 increased the productivity of PLP. Cycloheximide inhibited
      the increase of PLP by the oxidative stress and, in contrast, increased
      pyridoxine.

PMID- 11577720
TI  - Improvement of freezing tolerance in transgenic tobacco leaves by expressing the
      hiC6 gene.
AB  - A cryoprotective protein, HIC6, was expressed transgenically in tobacco, a cold
      sensitive plant, and the localization of the protein within the cell as well as
      freezing tolerance of the transgenic tobacco was investigated. For constitutive
      expression of HIC6 in tobacco, its corresponding gene was subcloned into pBI121.
      Through the transformation with pBI121/hiC6, fifteen transgenic tobacco lines
      were acquired, out of which twelve lines expressed the HIC6 protein. None of the
      transgenic tobacco lines, however, showed significant differences in freezing
      tolerance from the control plants (wild-type and transformed with pBI121) at -1, 
      3, and -4 degrees C, with the exception that their freezing temperature was -2
      degrees C. In order to increase the accumulation level of HIC6, pBE2113 with a
      stronger promoter was used. Eight lines expressed the protein out of thirteen
      lines transformed with pBE2113/hiC6. The accumulation levels of the protein were
      clearly higher in the tobacco plants transformed with pBE2113/hiC6 than in those
      with pBI121/hiC6. The HIC6 protein seemed to be localized in mitochondria of the
      transgenic tobacco plants. Freezing-tolerance tests at -1 - -4 degrees C showed
      that the degree of electrolyte leakage was significantly lower in the plants with
      pBE2113/hiC6 than in the control plants. A leaf browning observation also showed
      that high accumulation of HIC6 significantly suppressed injury caused by freezing
      to the transgenic tobacco at -3 degrees C.

PMID- 11577721
TI  - Structural confirmation of 15-norlubiminol and 15-norepilubiminol, isolated from
      Solanum aethiopicum, by chemical conversion from lubimin and epilubimin, and
      their antifungal activity.
AB  - 15-Norlubiminol and 15-norepilubiminol were obtained from Solanum aethiopicum as
      an inseparable 1:1 mixture in a relatively poor yield to that of the major
      phytoalexins, lubimin and epilubimin. Their structures were confirmed by chemical
      conversion starting from lubimin and epilubimin. Baeyer-Villiger oxidation of the
      protected lubimins with m-chloroperoxybenzoic acid provided the desired formates.
      Deoxygenation with triphenylphosphine selenide and subsequent methanolysis
      provided 15-norlubiminols, whose 1H-NMR spectra were respectively identical with
      that of the corresponding isomer in the natural 15-norlubiminol mixture. The
      antifungal activity of 15-norlubiminols would be weaker than that of lubimins.

PMID- 11577722
TI  - Characterization of clofibrate-induced retrograde Golgi membrane movement to the
      endoplasmic reticulum: clofibrate distinguishes the Golgi from the trans Golgi
      network.
AB  - Clofibrate-induced retrograde Golgi membrane movement was blocked or retarded
      when NRK cells were treated with sodium azide/2-deoxyglucose, nocodazole, taxol,
      and destruxin B, indicating that it depends on energy, and the dynamic state of
      microtubules, and being acidic or vacuolar-type ATPase function. PDMP and
      phospholipase A2 inhibitors also blocked it. These characteristics are similar to
      those of brefeldin A (BFA) and nordihydroguaiaretic acid (NDGA), inducers of
      retrograde Golgi membrane movement. However, clofibrate was distinguished from
      BFA in that BFA action was insensitive to phospholipase A2 inhibitors and from
      NDGA in that NDGA stabilized microtubules against nocodazole and its action was
      almost insensitive to taxol. The trans Golgi network (TGN) was resistant to
      clofibrate, while BFA and NDGA dispersed it. To our knowledge, clofibrate is the
      first drug to show such different effects on the Golgi and TGN and, therefore, is
      expected to be a useful tool to distinguish their architecture and/or membrane
      dynamics.

PMID- 11577723
TI  - Cloning, sequencing, and expression of the gene encoding an intracellular beta-D
      xylosidase from Streptomyces thermoviolaceus OPC-520.
AB  - The intracellular beta-xylosidase was induced when Streptomyces thermoviolaceus
      OPC-520 was grown at 50 degrees C in a minimal medium containing xylan or
      xylooligosaccharides. The 82-kDa protein with beta-xylosidase activity was
      partially purified and its N-terminal amino acid sequence was analyzed. The gene
      encoding the enzyme was cloned, sequenced, and expressed in Escherichia coli. The
      bxlA gene consists of a 2,100-bp open reading frame encoding 770 amino acids. The
      deduced amino acid sequence of the bxlA gene product had significant similarity
      with beta-xylosidases classified into family 3 of glycosyl hydrolases. The bxlA
      gene was expressed in E. coli, and the recombinant protein was purified to
      homogeneity. The enzyme was a monomer with a molecular mass of 82 kDa. The
      purified enzyme showed hydrolytic activity towards only p-nitrophenyl-beta-D
      xylopyranoside among the synthetic glycosides tested. Thin-layer chromatography
      analysis showed that the enzyme is an exo-type enzyme that hydrolyze
      xylooligosaccharides, but had no activity toward xylan. High activity against
      pNPX occurred in the pH range 6.0-7.0 and temperature range 40-50 degrees C.

PMID- 11577724
TI  - A recombinant molt-inhibiting hormone of the kuruma prawn has a similar secondary
      structure to a native hormone: determination of disulfide bond arrangement and
      measurements of circular dichroism spectra.
AB  - In crustaceans, molt-inhibiting hormone (MIH) is presumed to regulate molting
      through suppressing synthesis and/or secretion of ecdysteroids by the Y-organ.
      Recently, a recombinant MIH of the kuruma prawn Penaeus japonicus was produced in
      E. coli. To approximate the secondary structure of native and recombinant MIH of
      P. japonicus containing six cysteine residues, the arrangements of disulfide
      bridges in both MIHs were determined by characterizing their enzymatic digests,
      and their circular dichroism spectra were measured. The arrangements of disulfide
      bonds in both MIHs were determined to be identical, and they were linked between
      Cys7 and Cys44, Cys24 and Cys40, and Cys27 and Cys53. The circular dichroism
      spectra of both MIHs were very close, and demonstrated that they were rich in a
      helix. a-Helix contents in native and recombinant MIHs were calculated to be
      49.3% and 46.0%, respectively. All these results strongly suggested that the
      recombinant MIH was folded in the same manner as the native MIH.

PMID- 11577725
TI  - Purification and structural determination of a phosphorylated peptide with anti
      calcification and chitin-binding activities in the exoskeleton of the crayfish,
      Procambarus clarkii.
AB  - Organic matrices in calcified hard tissues have been considered to control
      calcification. A matrix peptide, designated CAP-1, was extracted and purified by
      anion-exchange and reverse-phase high performance liquid chromatographies from
      the exoskeleton of the crayfish, Procambarus clarkii. The amino acid sequence of
      CAP-1 was determined by mass spectral and sequence analyses of the intact peptide
      and its enzymatically digested peptides. CAP-1 consisted of 78 amino acid
      residues, including a phosphoserine residue, and was rich in acidic amino acid
      residues. CAP-1 had a Rebers-Riddiford consensus sequence, which is conserved in
      cuticle proteins from many arthropods. CAP-1 inhibited precipitation of calcium
      carbonate in an in vitro anticalcification assay dose-dependently, and completely
      inhibited it at 3 x 10(-7) M. CAP-1 also showed chitin-binding ability,
      indicating that this molecule was bifunctional and played an important role in
      formation of the exoskeleton.

PMID- 11577726
TI  - Electron transport inhibitor in Cyperus javanicus.
AB  - The natural quinone, hydroxydietrichequinone (3-heptadec-8-enyl-2-hydroxy-5
      methoxy-[1,4]benzoquinone) is a secondary metabolite of Cyperus javanicus. We
      found that this quinone inhibited both mitochondrial respiration and
      photosynthesis in their electron transportation systems. The quinone was found to
      have a mode of action against the ubiquinone reductase site from the results of
      different electron donor experiments on intact mitochondria from rat liver. The
      electron transport system, photosystem-II (PS-II), in chroloplast from spinach
      leaves was inhibited by the quinone in a similar way to that of the triazin sires
      herbicide, atrazin, with its mode of action against PS II. This natural quinone
      has a long aliphatic chain (C17) including an unsaturated bond at its midpoint.
      We recognized 8-9 unsaturated bonds in the aliphatic chain from an MS analysis of
      the methylthio-addact, and spectral data presumed a configuration of cis. form.

PMID- 11577727
TI  - Active oxygen radicals induce peroxidase activity in rice blade tissues.
AB  - The relationship between active oxygen radicals and peroxidase induction on
      disease resistance in rice blades was investigated. Nitric oxide was produced in
      the whole blade stimulated by blast fungus elicitor. The induction of peroxidase
      activity was detected in active oxygen radical-treated rice blades 1 hour after
      treatment and thereafter. These results suggest that active oxygen radicals
      produced by stimulation with the elicitor could trigger peroxidase induction.

PMID- 11577728
TI  - Isolation and structure elucidation of a new antifungal and antibacterial
      antibiotic produced by Streptomyces sp. 201.
AB  - An antibacterial and antifungal antibiotic was isolated from the culture filtrate
      of Streptomyces sp. 201, and its structure was determined as 2-methyl-heptyl
      isonicotinate by extensive use of NMR spectroscopy. The compound exhibited marked
      antimicrobial activity against Bacillus subtilis, Shigella sp., Klebsiella sp.,
      E. coli, Proteus mirabilis, and the pathogenic fungi, Fusarium moniliforme, F.
      semitectum, F. oxysporum, F. solani and Rhizoctonia solani.

PMID- 11577729
TI  - Inhibitory effects of capsaicinoids on fatty acid desaturation in a rat liver
      cell line.
AB  - The inhibitory effects of such vanillylamides as capsaicin and nine capsaicinoids
      on fatty acid desaturation in liver cells were investigated by using the cultured
      rat liver cell line, BRL-3A. When capsaicin was added to the medium, it had a
      relatively strong inhibitory effect on delta6 desaturation and clear inhibitory
      effects on delta5 and C24delta16 desaturation (delta16 desaturation of C24
      polyunsaturated fatty acids). Capsaicinoids with side carbon chain lengths of
      C10:0 and C12:0 expressed the maximum inhibitory effects of the nine
      capsaicinoids on fatty acid desaturation in the BRL-3A cells. The inhibitory
      effects of the capsaicinoids were not correlated with their pungency.

PMID- 11577730
TI  - Prevention by lactic acid bacteria of the oxidation of human LDL.
AB  - Ether extracts of lactic acid bacteria were analyzed for prevention of the
      oxidation of erythrocyte membrane and human low-density lipoprotein in vivo.
      Streptococcus thermophilus 1131 and Lactobacillus delbrueckii subsp. bulgaricus
      2038, yogurt starters, were chosen as test-strains, and ether extracts of these
      cultures were used as samples. Both strain 1131 and strain 2038 produced radical
      scavengers and inhibited oxidation of erythrocyte membranes and low-density
      lipoproteins. The antioxidative activity of strain 2038 was higher than that of
      strain 1131.

PMID- 11577731
TI  - Ellagic acid formation from galloylglucoses by a crude enzyme of Cornus capitata
      adventitious roots.
AB  - The aqueous extract of acetone powder, which had been prepared from Cornus
      capitata 'Mountain Moon' adventitious roots, cultured in MS medium with a high
      concentration of Cu2+(10 microM), showed strong oxidative activity toward
      galloylglucoses. A compound formed from galloyglucoses, such as 1,2,3,4,6-penta-O
      galloyl-beta-D-glucose and tannic acid, by the reaction with the crude enzyme
      solution of the adventitious roots was isolated and characterized as ellagic acid
      by spectrometric analyses.

PMID- 11577732
TI  - Role of activity of gastrointestinal microflora in absorption of calcium and
      magnesium in rats fed beta1-4 linked galactooligosaccharides.
AB  - Rats fed a diet containing beta1-4 linked galactooligosaccharides (GOS) (5 g/100
      g of diet) absorbed calcium and magnesium more efficiently than those fed the
      control diet. However, the increment obtained through GOS-feeding was reduced by
      neomycin sulfate (0.67 g/100 g of diet). Since the decrease in cecal pH in rats
      fed GOS was suppressed by neomycin-feeding, bacterial action in the digestive
      tract was considered to be reduced by neomycin-feeding. Our findings suggest that
      the action of intestinal bacteria is necessary for the effects of GOS.

PMID- 11577733
TI  - Purification and characterization of L-2,3-butanediol dehydrogenase of
      Brevibacterium saccharolyticum C-1012 expressed in Escherichia coli.
AB  - The L-2,3-butanediol dehydrogenase produced in E. coli JM109/pLBD2-CTC was
      purified by 5 steps. The molecular mass of this enzyme was estimated at 110 kDa
      and the subunit was measured to be 30 kDa. The L-BDH had some differences from
      the BDHs from other sources in substrate specificity, pI value, pH stability,
      effects of divalent cations, and organic acids.

PMID- 11577734
TI  - Synthesis of the L-enantiomer of 4'-C-ethynyl-2'-deoxycytidine.
AB  - The L-enantiomer of 4'-C-ethynyl-2'-deoxycytidine (2) was synthesized, but did
      not show any activity against HIV-1 up to 100 microM.

PMID- 11577735
TI  - Chitinase in cucumber xylem sap.
AB  - A chitinase activity was detected in fractions of xylem sap collected from the
      cut surface of cucumber stems. A 28-kDa acidic protein was purified from the
      active fractions and its N-terminal amino acid sequence was found to be identical
      to that of a chitinase gene. Cucumber roots produce and secrete an acidic
      chitinase, one of the PR proteins, into xylem sap and deliver it to aboveground
      organs.

PMID- 11577736
TI  - Specific antimicrobial synergism of synthetic hydroxy isothiocyanates with
      aminoglycoside antibiotics.
AB  - Hydroxy isothiocyanates, especially 2-(4-hydroxyphenyl)ethyl isothiocyanate
      (hITC), were examined for antimicrobial synergism with several antibiotics
      against Escherichia coli and Staphylococcus aureus, using a multiwell plate
      system. hITC had antibacterial synergism, specifically with aminoglycoside
      antibiotics. The synergism was observed in synthetic medium (M9 minimal medium)
      or soybean casein digest broth, but not in nutrient broth. Synergism was seen in
      the presence of certain sugars such as glucose, fructose, and maltose in the
      medium.

PMID- 11577737
TI  - Increased transglycosylation activity of Rhodotorula glutinis endo-beta-glucanase
      in media containing organic solvent.
AB  - The transglycosylation of p-nitrophenyl-beta-D-cellotrioside to cellotetraose
      catalyzed by endo-1,4-beta-glucanase (cellulase, EC 3.2.1.4) from a
      psychrotrophic yeast, Rhodotorula glutinis KUJ 2731, was increased by addition of
      a miscible organic solvent in the reaction mixture. Among various organic
      solvents tested, acetone was most effective. The transglycosylation activity
      increased with an increase in acetone concentrations, while hydrolysis activity
      was suppressed. The transglycosylation preferably occurred at acidic pH with the
      optimum pH at 2 in 10 mM Gly-HCl buffer. The optimum temperature of
      transglycosylation was found to be 50 degrees C in the presence of 40% acetone.

PMID- 11577738
TI  - Effect of germanium-132 on low-density lipoprotein oxidation and atherosclerosis
      in Kurosawa and Kusanagi hypercholesterolemic rabbits.
AB  - Germanium-132 (Ge-132) was given at 200 mg/kg of body weight to 8-week-old
      Kurosawa and Kusanagi hypercholesterolemic (KHC) rabbits. Thirty-six weeks later,
      the susceptibility of plasma low-density lipoprotein to oxidation and the
      morphology of atherosclerosis in the aorta and coronary artery were investigated.
      Treatment with Ge-132 resulted in decreases in the oxidation rate and in the
      formation rate of thiobarbituric acid-reactive substances following copper
      induced oxidation of LDL. Ge-132 is suggested to possess antioxidative
      properties, but this did not lead to any attenuation of atherosclerotic
      progression in the KHC rabbits.

PMID- 11577739
TI  - Enzymatic glycosylation of lincomycin.
AB  - Lincomycin (1), a glycosidic antibiotic, active against Gram-positive bacteria,
      was modified enzymatically with the aim of improving its physico-chemical and
      biological properties. Compound 1 was glycosylated using jack bean alpha
      mannosidase to produce 7-O-alpha-D-mannopyranosyl-lincomycin (2).

PMID- 11577740
TI  - Influences of nitrogen sources on usnic acid production in a cultured Mycobiont
      of the lichen Usnea hirta (L.) Wigg.
AB  - Effects of the nitrogen sources in the medium for the production of secondary
      metabolites in lichens were examined. The usnic acid production by a mycobiont of
      the lichen Usnea hirta was higher in the liquid medium containing ammonium and
      nitrate ions than in those containing amino acids.

PMID- 11577741
TI  - Enantioselective synthesis of ancepsenolide and its analogs.
AB  - Ancepsenolide (1a-s) and the enantiomer (1a-r) were respectively synthesized from
      (S)- and (R)-2-[(R)-O-MEM-mandeloyloxylpropanal (3a-s and 3a-r) and diisopropyl
      hexadecanedioate (5). The analogs (1b, 2a and 2b) were synthesized by a similar
      method.

PMID- 11577742
TI  - Multiplicity of aromatic ring hydroxylation dioxygenase genes in a strong PCB
      degrader, Rhodococcus sp. strain RHA1 demonstrated by denaturing gradient gel
      electrophoresis.
AB  - To address the multiplicity of aromatic ring hydroxylation dioxygenases, we used
      PCR amplification and denaturing gradient gel electrophoresis (DGGE). The
      amplified DNA fragments separated into five bands, A to E. Southern hybridization
      analysis of RHA1 total DNA using the probes for each band showed that band C
      originated from a couple of homologous genes. The nucleotide sequences of the
      bands showed that bands A, C, and E would be parts of new dioxygenase genes in
      RHA1. That of band B agreed with the bphA1 gene, which was characterized
      previously. That of band D did not correspond to any known gene sequences. The
      regions including the entire open reading frames (ORFs) were cloned and
      sequenced. The nucleotide sequences of ORFs suggested that the genes of bands A,
      C, and E may respectively encode benzoate, biphenyl, and polyhydrocarbon
      dioxygenases. Northern hybridization indicated the induction of the gene of band
      A by benzoate and biphenyl, and that of the gene of band C by biphenyl and
      ethylbenzene, supporting the above notions. The gene of band E was not induced by
      any of these substrates. Thus the combination of DGGE and Southern hybridization
      enable us to address the multiplicity of the ring hydroxylation dioxygenase genes
      and to isolate some of them.

PMID- 11577743
TI  - Mutational analyses of Dictyostelium IQGAP-related protein GApa: possible
      interaction with small GTPases in cytokinesis.
AB  - GAPA is an IQGAP-related protein and is involved in Dictyostelium cytokinesis.
      Since mammalian IQ-GAPs are effectors for Rac/Cdc42, GAPA is also predicted to
      bind to small GTPases, which are to be identified. In this study, mutant GAPAs
      were examined for functions in cytokinesis by genetic complementation of gapA-
      cells. Positively charged side chains of Arg442 and Lys474 of GAPA, predicted to
      be present on the surface of interaction with small GTPases, were found to be
      essential, suggesting an interaction between GAPA and putative small GTPase in
      cytokinesis. Also, results from truncated GAPAs indicated that almost the entire
      region of GAPA homologous to IQGAP is required for cytokinesis in Dictyostelium.

PMID- 11577744
TI  - A new double coupling system: synthesis of citronellyl acetate via
      transacetylation to citronellol from acetyl coenzyme A produced from glucose and
      free fatty acids.
AB  - A double coupling system, which couples metabolism of glucose and
      transacetylation, is a unique procedure for the production of acetic esters. In
      the novel coupling system described in this article, acetyl coenzyme A (acetyl
      CoA) was supplied via metabolism of both glucose and exogenous saturated fatty
      acids. While short and middle chain fatty acids having C4-8 were very biotoxic,
      myristic acid (C14) was effectively used as a source of acetyl-CoA.

PMID- 11577745
TI  - NMR determination of the absolute configuration of a macrophomate synthase
      inhibitor by using an axial chiral reagent.
AB  - Macrophomate synthase catalyzes an extraordinary four-step transformation from
      oxalacetate and 2-pyrone to macrophomic acid by an intermolecular Diels-Alder
      reaction. The absolute configuration of the most potent macrophomate synthase
      inhibitor; (-)-2-carboxylmethyl-1-methoxybicyclo[2.2.2]oct-5-ene-2-carboxylic
      acid, was determined to be (1S, 2R, 4R) by using an axial chiral reagent.

PMID- 11577746
TI  - Suppressive effect of coffee on lipopolysaccharide-induced hepatitis in D
      galactosamine-sensitized rats.
AB  - A coffee extract significantly suppressed lipopolysaccharide (LPS)-induced
      hepatitis in D-galactosamine-sensitized rats, as assessed by the plasma alanine
      and aspartate aminotransferase activities, when it was added to the diet (30
      g/kg) and fed to rats for 14 days. Its effect was as strong as that of a green
      tea extract. The coffee extract suppressed LPS-induced hepatitis when singly
      force-fed (1.2 g/kg) 1.5 h prior to the injection of the drugs, whereas a
      decaffeinated coffee extract had no significant effect. The hepatoprotective
      effect of caffeine was stronger than that of theobromine. These results indicate
      that coffee can protect animals from LPS-induced hepatitis, and that the effect
      of coffee might be mainly due to caffeine.

PMID- 11577747
TI  - A transformation system for an ectomycorrhizal basidiomycete, Lyophyllum shimeji.
AB  - A transformation vector, pLS-hph, was constructed with the promoter and
      terminator of the glyceraidehyde-3-phosphate dehydrogenase (GPD) gene derived
      from an ectomycorrhizal basidiomycete, Lyophyllum shimeji, and with the
      hygromycin B (HmB) phosphotransferase (hph) gene from Escherichia coli. This
      vector was introduced into protoplasts of L. shimeji and 3.4 transformants per
      microg plasmid DNA were obtained. In most of the transformants, multiple copies
      of the vector were integrated into the genomic DNA. The results indicate that pLS
      hph is a useful vector for L. shimeji.

PMID- 11577748
TI  - Hemicrania continua is not that rare.
AB  - BACKGROUND: Hemicrania continua is an indomethacin-responsive headache disorder
      characterized by a continuous, moderate to severe, unilateral headache. More than
      90 cases of hemicrania continua have been reported, but there is still
      uncertainty about its clinical features. METHODS: The authors compared 34 new
      cases (24 women, 10 men) with previously reported cases. All the patients met
      Goadsby and Lipton's proposed criteria. The authors compared baseline (continuous
      background headache) and exacerbation (attacks of severe periods of headaches).
      RESULTS: The baseline headache was typically mild to moderate in intensity and
      usually not associated with severe disability. In contrast, the headache
      exacerbations were severe and associated with photophobia, phonophobia, nausea,
      and disability. At least one autonomic symptom was present in 25 patients (74%).
      Jabs and jolts were present in 14 patients (41%). The mean indomethacin dose was
      136.7 +/- 60 mg (range 25 to 225 mg). Twenty-four patients (70.6%) met
      International Headache Society criteria for migraine in their exacerbation
      period. Occipital tenderness was observed in 23 patients (67.6%). The temporal
      pattern was remitting in four patients (11.8%), continuous from onset in 18
      (52.9%), and continuous evolving from remitting in 12 (35.3%). CONCLUSION:
      Hemicrania continua is not a rare disorder. All cases of chronic unilateral daily
      headaches should receive an indomethacin trial early if not first in treatment.

PMID- 11577749
TI  - Risk and governance.

PMID- 11577750
TI  - [Neoadjuvant and adjuvant chemotherapy of locally advanced stomach cancer].

PMID- 11577751
TI  - An experimental study of the isotopic enrichment in Ar, Kr, and Xe when trapped
      in water ice.
AB  - The isotopic enrichment of argon, krypton, and xenon, when trapped in water ice,
      was studied experimentally. The isotopes were found to be enriched according to
      their (m1/m2)1/2 ratio. These enrichment factors could be useful for comparison
      among the uncertain cosmic or solar isotopic ratios, the hopeful in situ cometary
      ratio, and those in Earth's atmosphere, in the context of cometary delivery of
      volatiles to Earth.

PMID- 11577752
TI  - Vestiges of life in the oldest Greenland rocks? A review of early Archean geology
      in the Godthabsfjord region, and reappraisal of field evidence for > 3850 Ma life
      on Akilia.
AB  - The Godthabsfjord region of West Greenland contains the most extensive, best
      exposed and most intensely studied early Archean rocks on Earth. A geological
      record has been described of numerous magmatic events between ~3.9 and 3.6 Ga,
      and evidence of life at >3.85 Ga and ~3.8-3.7 Ga has been proposed from two
      widely-separated localities. Some of these claims have recently been questioned,
      and the nature of the best preserved remnants of the oldest known terrestrial
      volcanic and sedimentary rocks in the Isua greenstone belt are being
      reinvestigated and substantially reinterpreted. The first part of this article
      reviews the evolution of geological research and interpretations, outlining the
      techniques by which the geological history has been determined and the ensuing
      controversies. The second part re-examines crucial field evidence upon which the
      antiquity of the oldest terrestrial life is claimed from the island of Akilia.

PMID- 11577753
TI  - Program and Abstracts. Fifth Annual Meeting, American Society for Gravitational
      and Space Biology. October 25-28, 1989, Cocoa Beach, Florida.

PMID- 11577754
TI  - Alternating myocardial sympathetic neural function of athlete's heart in
      professional cycle racers examined with iodine-123-MIBG myocardial scintigraphy.
AB  - Myocardial sympathetic neural function in professional athletes who had the long
      term tremendous cardiac load has not been fully investigated by myocardial iodine
      123-metaiodobenzylguanidine (MIBG) uptake in comparison with power spectral
      analysis (PSA) in electrocardiography. Eleven male professional cycle racers and
      age-matched 11 male healthy volunteers were enrolled in this study. The low
      frequency components in the power spectral density (LF), the high frequency
      components in the power spectral density (HF), the LF/HF ratio and mean R-R
      interval were derived from PSA and time-domain analysis of heart rate variability
      in electrocardiography. The mean heart-to-mediastinum uptake ratio (H/M ratio) of
      the MIBG uptake, in professional cycle racers was significantly lower than that
      in healthy volunteers (p < 0.01) and HF power in professional cycle racers was
      significantly higher than that in healthy volunteers (p < 0.05). In the group of
      professional cycle racers, the H/M ratio showed a significant correlation with
      the R-R interval, as indices of parasympathetic nerve activity (r = 0.80, p <
      0.01), but not with the LF/HF ratio as an index of sympathetic nerve activity.
      These results may indicate that parasympathetic nerve activity has an effect on
      MIBG uptake in a cyclist's heart.

PMID- 11577755
TI  - Usefulness of tc-99m MIBI SPECT in predicting multidrug resistance gene
      expression levels in non-small cell lung cancer--a preliminary report.
AB  - In this study we investigated whether Tc-99m hexakis 2-methoxy isobutyl
      isonitnile (Tc-99m MIBI) single-photon emission computed tomography (SPECT) has a
      correlation with the multidrug resistance (MDRI) and multidrug resistance
      associated protein (MRP1) gene expression levels in non-small cell lung cancer
      (NSCLC). Fifteen patients with NSCLC were studied. SPECT images were obtained 15
      (early) and 120 (delayed) min after injection of Tc-99m MIBI. We chose only one
      transverse section and set the region of interest over the tumor and out of the
      body. The mean counts in the tumor on early and delayed images were corrected by
      using those in the background and represented as Te and Td, respectively.
      Resected tumor specimens were frozen with liquid nitrogen and each positive
      control cell line was cultured. After the total ribonucleic acid (RNA) was
      extracted from specimens and cell lines, the complimentary deoxyribonucleic acid
      (cDNA) was amplified by the reverse transcription-polymerase chain reaction (RT
      PCR) method. Each product was electrophoresed and fluorointensity was measured.
      The gene expression level was represented as the ratio of that of the positive
      control cell line. Te and Td indicated a significant correlation with the MDR1
      gene expression level (p = 0.015 and p = 0.022), but not the gene of MRP1 (p =
      0.100 and p = 0.145). In conclusion, Te and Td are useful parameters in
      predicting the MDRI gene expression level, but not MRPI in NSCLC.

PMID- 11577756
TI  - Is technetium-99m-MIBI taken up by the normal pituitary gland? A comparison of
      normal pituitary glands and pituitary adenomas.
AB  - PURPOSE: The aim of this study was to compare the behavioral uptake of a normal
      gland and a pituitary adenoma and to assess the ability to diagnose pituitary
      adenoma by means of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (MIBI)
      single photon emission computed tomography (SPECT). METHODS: The study included
      15 patients with pituitary adenomas (mean age = 44.0 years, range 19-63) and 15
      control subjects (mean age = 50.7 years, range 20-67). SPECT was performed 15
      minutes after an intravenous injection of MIBI 600 MBq. The shape and location of
      MIBI uptake were evaluated on a magnetic resonance (MR) imaging/SPECT
      registration image. The shape patterns and location were classified as follows:
      Shape C (circular); LO (longitudinal oval); T/R (triangular or rectangular) and
      location P (pituitary gland or adenoma); D/C (dorsum sellae and/or clivus).
      RESULTS: Analysis of the uptake showed that 10 (67%) adenomas were C, and 5 (33%)
      were LO. Of the controls, 5 (33%) were C, and 10 (69%) were T/R. With regard to
      location, all patients with pituitary adenomas were classified as P, and all
      control subjects (93%) but one showed uptake in the dorsum sellae and clivus
      (D/C). CONCLUSION: MIBI was taken up in the dorsum sellae or clivus but not the
      normal pituitary gland and had a strong affinity for the pituitary adenoma. This
      result implies that MIBI SPECT may be a useful new auxiliary examination
      technique for the location diagnosis of pituitary adenoma.

PMID- 11577757
TI  - 99mTc-MIBI SPECT in small cell lung cancer patients before chemotherapy and after
      unresponsive chemotherapy.
AB  - We evaluated the accumulation of 99mTc-MIBI in small cell lung cancer patients
      before chemotherapy and after unresponsive chemotherapy. The pre-chemotherapeutic
      group included 22 newly diagnosed patients. These patients underwent a 99mTc-MIBI
      SPECT study before starting chemotherapy. After chemotherapy, based on changes in
      tumor size, three different patterns of response (complete remission: CR, partial
      remission: PR and no change: NC) were defined. The post-chemotherapeutic group
      included 11 patients after chemotherapy who did not respond to chemotherapy.
      These patients underwent a 99mTc-MIBI SPECT study after completion of
      chemotherapy. SPECT images were acquired 15 min (early) and 2 hr (delayed) after
      injection of 99mTc-MIBI. With a region of interest technique, the early ratio,
      delayed ratio and retention index were calculated. Early and delayed ratios in
      pre-chemotherapeutic patients were significantly higher than those in post
      chemotherapeutic patients. There were no significant differences between the pre
      chemotherapeutic and post-chemotherapeutic patients in the retention index. In
      the pre-chemotherapeutic patients, early and delayed ratios for the CR and PR
      groups were significantly higher than those for the NC group. There were no
      significant differences in the retention index with respect to the tumor
      response. 99mTc-MIBI might be useful for evaluating the tumor chemosensitivity in
      patients with small cell lung cancer.

PMID- 11577758
TI  - Dissociation of brain edema induced by cold injury in rat model: MR imaging and
      perfusion studies with 14C-iodo-antipyrine.
AB  - The purpose of this study is to confirm whether T2-weighted imaging and perfusion
      imaging, i.e. autoradiogram of 14C-iodoantipyrine, on the course of brain edema
      correspond to each other or not. Cold injured rat brains were used as a model and
      were sequentially examined by both methods and compared with each other and with
      histological specimens. Special focus relies on the time changes in the lesions.
      High SI of T2-weighted images were observed and the percentages in the high SI
      area to the total brain area in the same slice were 4.7 +/- 0.31, 5.6 +/- 0.46
      and 3.4 +/- 0.42 for 6, 24 and 48 hours, respectively. By contrast, low perfusion
      areas were indicated in the perfusion study and their percentages were 4.6 +/-
      0.55, 5.6 +/- 0.86 and 2.4 +/- 0.35 for 6, 24 and 48 hours, respectively. At 48
      hours after cold injury, low perfusion areas were smaller than hi

PMID- 11577759
TI  - Dynamic changes in cardiac fatty acid metabolism in the stunned human myocardium.
AB  - BACKGROUND: The chronological changes or mechanisms in cardiac fatty acid
      metabolism under clinical conditions of hypoxia and ischemia have not been fully
      elucidated. 123-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) can be
      used with single photon emission computed tomography (SPECT) to evaluate
      myocardial fatty acid metabolism. We investigated chronological changes in energy
      metabolism in the stunned human myocardium by means of 123I-BMIPP myocardial
      SPECT. METHODS AND RESULTS: We conducted 123I-BMIPP myocardial SPECT in 10
      patients with stunned myocardium during the acute, subacute and chronic phases
      after onset. The left ventricle was divided into 9 regions on SPECT, and the
      degree of abnormalities in each region was scored in four grades from normal (0)
      to defect (4). We also examined wash-out rates on BMIPP images. The scores on
      early BMIPP images in the acute, subacute and chronic phases were 5.6 +/- 1.8,
      13.4 +/- 3.5 and 2.5 +/- 1.1, respectively, and the score was highest in the
      subacute phase (p < 0.001). Similarly, scores on the late images were 2.3 +/-
      1.7, 18.3 +/- 4.5 and 4.7 +/- 2.6, respectively, and highest in the subacute
      phase (p < 0.001). The wash-out rates (normal: 18.2 +/- 2.1%) in the acute,
      subacute and chronic phases were 12.1 +/- 4.8%, 44.9 +/- 10.0% and 23.1 +/- 4.6%,
      respectively, with the value being lowest during the acute phase (p < 0.05), and
      highest during the subacute phase (p < 0.001). CONCLUSION: These results
      suggested that fatty acid metabolism in the stunned human myocardium changes
      dynamically over time.

PMID- 11577760
TI  - Assessment of ampulla (Takotsubo) cardiomyopathy with coronary angiography, two
      dimensional echocardiography and 99mTc-tetrofosmin myocardial single photon
      emission computed tomography.
AB  - We studied the causative mechanism of ampulla (Takotsubo) cardiomyopathy.
      METHODS: We examined 7 patients with ampulla cardiomyopathy by means of coronary
      angiography, two-dimensional echocardiography and 99Tc-tetrofosmin myocardial
      SPECT at the time of emergency admission (acute phase), at 3 to 5 days after the
      attack (subacute phase) and at 1 month after the attack (chronic phase). The left
      ventricle was divided into 9 regions on two-dimensional echocardiograms and 99mTc
      tetrofosmin myocardial SPECT images, then the degree of abnormalities in each
      region was scored in four grades from normal (0) to severely abnormal (3). We
      injected nicorandil into the coronary arteries and determined the elevation in
      the ST segment before and after administration. RESULTS: Coronary angiography did
      not show stenotic lesions in any patient. The acute, subacute and chronic phase
      myocardial perfusion scores on 99mTc-tetrofosmin myocardial SPECT were 11.2 +/-
      3.4, 2.7 +/- 2.3 and 0.4 +/- 0.5, respectively, and wall motion scores on
      echocardiograms were 13.0 +/- 3.6, 4.4 +/- 2.2 and 0.6 +/- 0.6, respectively,
      indicating improvement in all scores during the subacute phase (p < 0.01). The
      elevation in the ST segment (mm) on the electrocardiogram was improved from 8.3
      +/- 2.7 to 4.9 +/- 1.9 after the administration of nicorandil (p < 0.05).
      CONCLUSION: These findings indicated that coronary microvascular spasm is one
      causative mechanism of ampulla cardiomyopathy.

PMID- 11577761
TI  - Discordant iodine-123 metaiodobenzylguanidine uptake area reflects recovery time
      dispersion in acute myocardial infarction.
AB  - lodine-123 metaiodobenzylguanidine (MIBG) uptake was reported to be reduced
      compared to Tl-201 (Tl) in acute myocardial infarction (AMI). Within such an
      area, degrees of both sympathetic neural function and ischemic myocardial cell
      damage are considered to be greatly dispersed. These kinds of damage were
      reported to effect reporalization time in myocardial cells, and we evaluated our
      hypothesis that extension of the discordant MIBG uptake area correlates with
      recovery time (RT) dispersion and relate ventricular arrhythmias in AMI. MIBG and
      Tl images were obtained in AMI patients. Regional Tl or MIBG uptake was estimated
      in 9 segments of SPECT by using four-point scoring. The total score was the sum
      of scores in 9 SPECT segments. ATI-MIBG was calculated by subtracting the total
      MIBG score from the total Tl score. Corrected RT (RTc) was measured as a signal
      averaged ECG. RTc dispersion was defined as the difference between maximal and
      minimal RTc. The patients were assigned to two groups (group A; < or = Lown 4a,
      group B; > or = Lown 4b) according to the results of 24-hour Holter monitoring. A
      positive correlation between RTc dispersion and ATI-MIBG was found. ATI-MIBG and
      RTc dispersion in group B were greater than those in group A. These results
      suggested that ATI-MIBG could be used to predict the development of malignant
      ventricular arrhythmias.

PMID- 11577762
TI  - The usefulness of brain perfusion SPECT in an infant with focal convulsions
      associated with hemophilus influenzae central nervous system infection.
AB  - Left hemiconvulsions occurred in a 13-month-old girl with Hemophilus influenzae
      (H. influenzae) central nervous system (CNS) infection. Tc-99m HMPAO brain SPECT
      showed a focal hyperperfusion area in the right frontal lobe. The patient
      recovered without complications, and follow-up SPECT revealed markedly improved
      findings. Tc-99m HMPAO brain SPECT is useful for evaluating focal convulsions
      associated with H. influenzae CNS infection.

PMID- 11577763
TI  - Interictal crossed cerebellar hyperperfusion on Tc-99m ECD SPECT.
AB  - Crossed cerebellar hyperperfusion (CCH) in epilepsy is a rare condition that is
      observed on ictal cerebral perfusion SPECT. The mechanism of CCH assumes that
      hyperperfusion in the epileptic foci of the unilateral supratentorium causes
      hyperperfusion secondary to the corticopontocerebellar pathway (CPCP)-mediated
      remote effect in the contralateral cerebellar hemisphere. This phenomenon is
      similar to that of crossed cerebellar diaschisis (CCD). In this report we
      demonstrated interictal CCH in a patient with epilepsy in technetium-99m-ethyl
      cysteinate dimer (Tc-99m ECD) SPECT of the brain. To the best of our knowledge,
      interictal CCH has not been reported in the literature. This is the first report
      to describe the phenomenon with interictal Tc-99m ECD SPECT.

PMID- 11577764
TI  - Detection of denervated but viable myocardium in cardiac sarcoidosis with I-123
      MIBG and Tl-201 SPECT imaging.
AB  - A 58-year-old man, who had biopsy-proven cardiac sarcoidosis, underwent TI-201
      and I-123 MIBG cardiac scintigraphy. Although no perfusion defect was identified
      by Tl-201, mild heterogeneity of I-123 MIBG uptake was present in the myocardium.
      The denervated but viable myocardium was demonstrated in the heart with
      sarcoidosis. Cardiac sympathetic nerve function was impaired in cardiac
      sarcoidosis, slightly improved with steroid therapy. I-123 MIBG scintigraphy may
      be useful to assess extent of myocardial involvement and response to therapy.

PMID- 11577765
TI  - Inexplicable suppression of hepatic uptake of gallium-67, a case report.
AB  - We describe here a case report of a patient with acute lymphocytic leukemia in
      whom hepatic gallium-67 (Ga-67) uptake was suppressed. The patient was
      hospitalized with increasing dyspnea. In Ga-67 scintigraphy, there was no hepatic
      uptake, although other physiological uptake was clearly observed. In addition,
      the scintigraphy showed increased accumulation in the right lung consistent with
      infection. We considered possible reasons for these findings. The patient had no
      history of chemotherapy or blood transfusion, and his iron metabolism was almost
      normal. He was not receiving any medication which might reduce hepatic blood
      flow. Blood chemistry suggested normal hepatic and renal function. The patient
      died from pneumonia 6 weeks later. The autopsy revealed extensive infiltration of
      the right lung with Bacillus cereus (B. cereus). Metabolic acidosis and/or iron
      utilization of B. cereus may induce both increased Ga-67 accumulation in the
      infected lesion and suppressed uptake in the liver, but these mechanisms could
      not explain normal physiological uptake in the other organs. This case warranted
      the further study of the hepatic Ga-67 uptake mechanism.

PMID- 11577766
TI  - A case of double cancers with myocardial metastasis mimicking acute myocardial
      infarction both on an electrocardiogram and on Tc-99m-MIBI myocardial SPECT.
AB  - We report a rare case of double cancers with myocardial metastasis presenting
      acute myocardial infarction (AMI)-like findings both on an electrocardiogram
      (ECG) and on Tc-99m-MIBI myocardial SPECT. The ECG showed abnormal Q-waves and ST
      segment elevation in leads V1-V4, and Tc-99m-MIBI SPECT showed a photon deficient
      area in the anteroseptum. These findings were suggestive of AMI, but the patient
      had been simultaneously suffering from two adenocarcinomas, which were lung
      cancer and gastric cancer, and consecutive ultrasonic cardiography (UCG)
      demonstrated a growing mass lesion in the septal aspect of the left ventricle.
      After a month he died of severe heart failure. The histological diagnosis of a
      specimen of the cardiac mass lesion was invasive adenocarcinoma infiltrating to
      the heart, which revealed that the myocardial metastasis had mimicked AMI. This
      case shows that it is difficult to distinguish between myocardial infarction and
      myocardial metastasis with myocardial perfusion SPECT. It is necessary to
      consider the possibility of myocardial metastasis when a patient with malignancy
      presents AMI-like findings.

PMID- 11577767
TI  - High- and moderately high-methionine uptake demonstrated by PET in a patient with
      a subacute cerebral infarction.
AB  - In patients with cerebral tumors, high accumulations of L-methyl-11C-methionine
      (11C-Met) have been reported in some cases of cerebral ischemic disease, but no
      high accumulations of 11C-Met in areas where only transient arterial occlusions
      are most likely to occur have been reported. Herein we present a case of a high
      accumulation of 11C-Met in an area of frontal interhemispheric cerebral
      infarction and a moderately high accumulation with an unclear margin in a distant
      frontal convexity area. A craniotomy revealed a subacute stage of cerebral
      infarction in the interhemispheric lesion, and an ischemic change in the distant
      convexity area. Sixteen months after onset, CT scans demonstrated an infarction
      area in the interhemispheric lesion only, and no atrophic changes were observed
      in the distant convexity area indicating that no serious tissue damage had
      occurred.

PMID- 11577768
TI  - Detection of cold bone metastasis by Tc-99m MIBI imaging.
AB  - We present a case of renal cell carcinoma metastasis to the skull, appearing as a
      photopenic area on Tc-99m MDP bone scan and with focal uptake in the same region
      on Tc-99m MIBI imaging.

PMID- 11577769
TI  - 99mTc-sestamibi muscle scintigraphy to assess the response to neuromuscular
      electrical stimulation of normal quadriceps femoris muscle.
AB  - OBJECTIVES: Neuromuscular electrical stimulation (NMES) is widely used for
      improving muscle strength by simultaneous contraction in the prevention of muscle
      atrophy. Although there exist many clinical methods for evaluating the
      therapeutic response of muscles, 99mTc-sestamibi which is a skeletal muscle
      perfusion and metabolism agent has not previously been used for this purpose. The
      aim of our work was to ascertain whether 99Tc-sestamibi muscle scintigraphy is
      useful in the monitoring of therapeutic response to NMES in healthy women.
      METHODS: The study included 16 women aged between 21 and 45, with a mean age of
      32.7 +/- 6.4. Both quadriceps femoris muscles (QFM) of each patient were studied.
      After randomization to remove the effect of the dominant side, one QFM of each
      patient was subjected to the NMES procedure for a period of 20 days. NMES was
      performed with an alternating biphasic rectangular current, from a computed
      electrical stimulator daily for 23 minutes. After measurement of skinfold
      thickness over the thigh, pre- and post-NMES girth measurements were assessed in
      centimeters. Sixty minutes after injections of 555 MBq 99mTc-sestamibi, static
      images of the thigh were obtained for 5 minutes. The thigh-to-knee uptake ratio
      was calculated by semiquantitative analysis and normalized to body surface area
      (NUR = normalized uptake ratio). RESULTS: The difference between the pre and post
      NMES NUR values was significant (1.76 +/- 0.31 versus 2.25 +/- 0.38, p = 0.0000).
      The percentage (%) increase in NUR values also well correlated with the %
      increase in thigh girth measurements (r = 0.89, p = 0.0000). CONCLUSION: These
      results indicated that 99mTc-sestamibi muscle scintigraphy as a new tool may be
      useful in evaluating therapeutic response to NMES.

PMID- 11577770
TI  - Clinical diagnosis: muscular sarcoidosis.

PMID- 11577771
TI  - Opacification of artificial intraocular lens: an electron microscopic study.
AB  - This paper describes the usefulness of electron microscopy in the investigation
      of the cause of opacification of an intraocular artificial lens (IOL), which
      affected both the anterior and posterior surfaces of the IOL. The explanted
      lenses were remarkably similar and were uniformly opaque, with "reticulated"
      surfaces under dissecting and ordinary light microscopes. TEM showed that the
      surfaces of the explanted lenses were irregular, and there was a layer of
      electron-dense granular deposits that extended to a depth of approximately 5
      microm into the lens substance. SEM showed a "cerebriform" lens surface with
      elevated areas alternating with depressed crevices, which corresponded nicely to
      the TEM appearance. Energy-dispersive x-ray analysis showed that the deposit was
      composed of calcium, oxygen, and phosphorus, which was later shown to be calcium
      hydroxyapatite by x-ray diffraction study. Electron microscopy has proven to be
      an essential tool in the investigation of the cause of this mysterious outbreak
      of opacification of the surfaces of the artificial lenses. Apart from directly
      visualizing the lens surfaces in a 2- and 3-dimensional manner, it also provides
      information on the elemental composition of the deposit. Such findings enable the
      clinicians and manufacturer to search for the underlying pathogenesis of the
      abnormal calcium hydroxyapatite crystals deposit.

PMID- 11577772
TI  - Diagnostic value of electron microscopy in a case of juvenile neuronal ceroid
      lipofuscinosis.
AB  - Neuronal ceroid lipofuscinoses (NCLs) represent a large group of inherited
      neurodegenerative disorders characterized by an abnormal accumulation of
      lipopigment in neuronal and extraneuronal cells. The authors present a case of
      juvenile neuronal ceroid lipofuscinosis in a 7-year-old boy. Ultrastructural
      examination of a skin biopsy disclosed deposits of curvilinear profiles and
      fingerprint-like structures in epithelial cells of sweat glands, endothelial
      cells, peripheral nerve endings, and fibroblasts. These findings allowed specific
      confirmation of the assumed diagnosis of juvenile neuronal ceroid lipofuscinosis.
      Due to the genotypic and phenotypic variability within the group of NCLs, the
      clinical investigation may be long and complicated. With the NCL disorders in
      mind, an accurate diagnosis based on ultrastructural examination of a skin biopsy
      may shorten this investigation, thus benefitting the patient.

PMID- 11577773
TI  - Intercellular junctions, apical differentiation, and infiltrative features in
      colon cancer: an ultrastructural study. The Colon Cancer Team at IMAS.
AB  - Changes in the structure and number of cell junctions have been related to the
      infiltrative and metastatic potential of tumor cells. Apparently, the loss of
      cell adhesion should be coordinated with significant changes in the apical and
      basal cell domains. The authors have performed a sequential ultrastructural study
      of cells in the superficial, middle, and deep regions of well- and moderately
      differentiated colon adenocarcinomas. This was to investigate the differences in
      the organization of different membrane domains among tumor cells in the in situ
      areas, the advancing, infiltrative edge of the tumors, and the infiltrating zones
      between these two extreme zones. The results of the study suggest that the
      organization of these domains is not strictly coordinated, and that, for each
      infiltration level, both a settling and an infiltrating cell population can be
      found. These findings could explain the fact that apparently well-differentiated
      tumors are able to seed distant tissues with individual cells, rather than with
      well-differentiated glandular aggregates that would hardly be able to reach the
      vessel lumina without significantly modifying their organization.

PMID- 11577774
TI  - Interstitial capillary in normal and in transplanted kidneys: an ultrastructural
      study.
AB  - Knowledge about the normal structure and pathology of interstitial capillary is
      limited. Splitting and multilayering of the basal membrane (BM), as a marker of
      chronic rejection, has been published in association with transplant
      glomerulopathy. The authors investigated the ultrastructural features of the
      interstitial capillary basal membrane in normal (15 biopsies) and in transplanted
      kidneys (27 biopsies from 21 patients), expressing transplant glomerulopathy (8
      biopsies from 6 patients), acute tubulo-interstitial rejection (9 biopsies from 6
      patients), and recurrent or de novo glomerulonephritis (10 biopsies from 8
      patients). All biopsies were fixed in 1% OsO4, embedded in Epon, and examined by
      electron microscope. Measurements of the interstitial capillary BM were made. The
      BM of interstitial capillary of intact kidney was a homogenous continuous
      structure, 88 nm in width on average. Thickening with diffuse multilayering of BM
      was most intensive in patients with transplant glomerulopathy, and much less
      intensive in patients with acute tubulointerstitial rejection and in patients
      with recurrent or de novo glomerulonephritis. These findings may provide the
      first information about the morphology of the normal basal lamina of interstitial
      capillary and support the diagnostic value of interstitial capillary changes in
      chronic rejection.

PMID- 11577775
TI  - Ultrastructural telepathology--remote EM-diagnostic via Internet.
AB  - New collaboratory opportunities in ultrastructural research and diagnostics are
      now available on the Internet through the combination of digital image
      acquisition, remote operation of modern digitally controlled and automated
      electron microscopes, and the development of software specifically tailored for
      collaboratory needs. Remote experts can examine samples directly, and unique
      instruments can be utilized from anywhere. In the case of diagnostic dilemmas,
      the second-opinion expert is no longer constrained by problems inherent in the
      interpretation of preselected images. The remote examiner can independently
      choose the area of interest on the sample as well as select the appropriate
      magnification for an accurate diagnosis. With these capabilities and together
      with teleconferencing tools and securely accessible databases on-line,
      telepathology can provide increased effectiveness and support for diagnostics,
      research, and teaching in many areas. The authors report their experience with
      remote electron microscope diagnoses of pathological samples using two different
      dynamic imaging systems and discuss the main technical issues encountered. It
      appears that only minor technical issues need to be resolved before
      ultrastructural telepathology can be promoted for routine use in areas with high
      speed Internet access.

PMID- 11577776
TI  - Pituicytoma: ultrastructural evidence of a possible origin from folliculo
      stellate cells of the adenohypophysis.
AB  - Pituicytoma is a rare neoplasm occurring in the sellar and suprasellar regions.
      The tumor is currently considered to arise from the pituicyte, a specialized
      glial cell of the posterior lobe and the stalk of the pituitary gland. The
      authors describe a case of pituicytoma, focusing on the ultrastructural features.
      The patient was a 79-year-old woman with hypopituitarism and visual disturbances.
      Immunohistochemically, the tumor showed strong and diffuse positivity for
      vimentin, and EMA and GFAP were focally detectable. Ultrastructurally, the lesion
      was composed of elongated cells containing in the Golgi area aggregates of
      intermediate filaments in a concentric pathway (fibrous body), and secretory
      granules. These features intermediate between a pituicytoma and a pituitary
      adenoma suggest that "pituicytomas" may also arise from the specialized stromal
      folliculo-stellate cells of the adenohypophysis, which are able to differentiate
      into endocrine cells.

PMID- 11577777
TI  - Value of electron microscopy in the diagnosis of childhood nephrotic syndrome.
AB  - The value of the ultrastructural study of the renal biopsy was investigated in a
      series of pediatric patients with nephrotic syndrome. Forty-eight cases of renal
      biopsies with clinical data were reviewed and divided into diagnostic groups. The
      contribution of electron microscopy to the final diagnosis was graded as
      essential-diagnosis could not be reached without it; supportive-it increased the
      level of confidence in the final diagnosis; and noncontributory. In this series
      of renal biopsies from 48 children with nephrotic syndrome resistant or
      nonresponsive to therapy, the most frequent diagnosis was minimal change disease,
      present in 42% of the patients. The contribution of the electron microscopic
      study to the final diagnosis was essential in 73% of the series, and was
      supportive in a further 27%. Therefore, it is concluded that the ultrastructural
      study was an essential component in the study of the renal biopsy in children
      with nephrotic syndrome, suggesting that electron microscopy needs to continue to
      be performed for all these patients.

PMID- 11577778
TI  - Lipoblastoma and lipoblastomatosis in infancy and childhood: histopathologic,
      ultrastructural, and cytogenetic features.
AB  - Lipoblastoma is a relatively rare tumor that occurs in infancy and early
      childhood and arises from embryonic white fat. Although a benign tumor,
      lipoblastomas tend to recur and may resemble myxoid liposarcoma. The authors
      report 26 cases over a 15-year period at Texas Children's Hospital. There was a
      slight female predilection (14F:12M). The most common symptom was a painless mass
      with or without increasing size. The trunk, extremities, head and neck,
      retroperitoneum, inguinal canal, peritoneal cavity, and lung were the tumor
      sites. Most tumors were circumscribed lipoblastomas and the minority were diffuse
      infiltrative lipoblastomatosis. Reexcision for residual or recurrent tumor was
      necessary more frequently in patients with lipoblastomatosis. Histopathologic
      examination and ultrastructural examination revealed cellular neoplasms composed
      of immature adipocytes with relatively well-defined septa, frequent lipoblasts, a
      fine vascular network, and often a myxoid appearance resembling myxoid
      liposarcoma. Cytogenetics was performed in 4 cases with chromosome 8q abnormality
      being most common. The major concern with lipoblastoma in children is to
      completely excise the tumor to avoid leaving residual tumor and to prevent
      recurrences. Confusion with myxoid liposarcoma, well-differentiated liposarcoma,
      and typical lipomas may occur. Although asymptomatic, lipoblastomas may cause
      dysfunction of other organ systems due to mass effect. Complete surgical excision
      with at least 2 years of follow-up is the preferred therapy.

PMID- 11577779
TI  - Mechanism of permissive prostacyclin action in cerebrovascular smooth muscle.
AB  - Prostacyclin permissively allows increased cAMP and cerebral vasodilation to
      hypercapnia in piglets. The prostacyclin receptor (IP) is coupled to
      phospholipase C (PLC) in piglet cerebral microvascular smooth muscle cells (SMC).
      We hypothesize that inhibition of PLC blocks the permissive action of IP receptor
      agonist, iloprost, and direct activation of PKC substitutes for the IP receptor
      agonist in SMC. SMC cAMP production was measured at normal pHi/pHo and with
      reduced pHi/pHo in the absence and presence of iloprost (100 pM). Half of the
      cells were pretreated with U73122, the PLC inhibitor, which decreased the basal
      IP3 and blocked the increase in IP3 caused by iloprost. Without iloprost,
      decreasing pHi/pHo increased cAMP production (40%). With iloprost, the cAMP
      response to acidosis increased to over 80%. U73122 prevented accentuation of the
      cAMP response by iloprost. Phorbol myristate acetate augmented the response to
      acidosis similarly to iloprost. These data suggest IP agonists augment the cAMP
      response to acidosis via coupling through PLC to activate PKC.

PMID- 11577780
TI  - Developmental maturation of primate placental trophoblast: placental cytosolic
      and secretory phospholipase A2 expression after estrogen suppression of baboons.
AB  - We have demonstrated that the baboon placenta expressed the mRNAs and proteins
      for secretory and cytosolic phospholipase A2 (PLA2) enzymes and that cPLA2
      expression increased with advancing gestation in association with the increase in
      placental estrogen production. To determine whether estrogen regulates placental
      PLA2 expression, as it does other aspects of syncytiotrophoblast functional
      differentiation, we compared sPLA2 and cPLA2 mRNA levels in placentas obtained on
      day 165 of gestation (term = day 184) from baboons that were untreated or treated
      during the second half of gestation with the aromatase inhibitor CGS 20267 or CGS
      20267 and estradiol. Maternal saphenous and uterine vein estradiol levels were
      reduced (P < 0.05) by approximately 95% by treatment with CGS 20267 and restored
      by concomitant administration of CGS 20267 and estrogen. However, sPLA2 and cPLA2
      mRNA levels expressed as a ratio of beta-actin were similar in whole villous
      placenta from baboons that were untreated or treated with CGS 20267 or CGS 20267
      plus estrogen. PLA2 expression in an enriched fraction of nontrophoblast cells of
      the baboon placenta was also not altered by CGS 20267 treatment. Collectively
      these findings indicate that placental cPLA2 and sPLA2 expression is not estrogen
      dependent. Because estrogen has been shown to regulate other aspects of placental
      steroidogenesis, we suggest that the regulatory role of estrogen on
      syncytiotrophoblast functional maturation is specific.

PMID- 11577781
TI  - Prostaglandin-J2 induces synthesis of interleukin-8 by endothelial cells in a
      PPAR-gamma-independent manner.
AB  - PPARgamma is a transcription factor of nuclear receptor superfamily, involved in
      the regulation of inflammation. We investigated the influence of PPARgamma
      ligands, 15-deoxy-delta12,14 prostaglandin-J2 (15d-PGJ2), and ciglitazone, on the
      generation of interleukin-8 (IL-8) by the human microvascular endothelial cell
      line (HMEC- 1). Expression of PPARgamma in HMEC-1 was confirmed by RT-PCR. Both
      PPARgamma-ligands tested induced the activation of PPAR, but the potency of
      ciglitazone was higher, as evidenced by luciferase assay. Resting HMEC-1 released
      about 150 pg/ml of IL-8 protein. Treatment with LPS increased the IL-8 secretion
      up to 1 ng/ml. 15d-PGJ2 potently and dose-dependently increased both the steady
      state and LPS-induced generation of IL-8 mRNA and IL-8 protein. In contrast,
      neither basal nor LPS-elicited expression of IL-8 was influenced by ciglitazone.
      We conclude, that 15d-PGJ2 is a potent inducer of IL-8 production and can be a
      mediator of inflammatory response, but this effect is independent of PPARgamma
      activation.

PMID- 11577782
TI  - Interrelationship between nitric oxide and prostaglandins in bovine granulosa
      cells.
AB  - It is well recognized that prostaglandins of the E (PGE) and F (PGF) series play
      an important role in ovarian physiology; in addition, nitric oxide (NO) has been
      recently demonstrated to be an important mediator of granulosa cell function.
      There is now evidence for a biologic relationship between PGs and the NO
      biosynthetic pathway. The aim of this study was to investigate the relationship
      between NO and PGE2 and PGF2alpha in bovine granulosa cells. Granulosa cells
      collected from small (<5mm) and large (>8mm) follicles were treated with the NO
      donor S-nitroso-N-acetylpenicillamine (SNAP) or with indomethacin, an inhibitor
      of PGs synthesis, and PGE2 and PGF2alpha were quantified; in addition, the
      effects of PGE2 PGF2alpha and indomethacin on steroidogenesis and NO production
      were determined. The highest concentration of SNAP inhibited (P < 0.001) PGE2
      production in cells from both kinds of follicles, while the lowest dose was
      effective only in cells from small follicles. The highest concentration of SNAP
      inhibited and stimulated (P < 0.001) PGF2alpha production in cells from small and
      large follicles, respectively. Progesterone (P4) production was stimulated by
      PGE2 and inhibited by PGF2alpha (P < 0.001) in cells from both types of
      follicles. Estradiol 17beta (E2) secretion was inhibited in cells from small and
      stimulated in those from large follicles by PGE2 (P < 0.05), while PGF2alpha was
      stimulatory in cells from both kinds of follicles (P < 0.001). P4 production by
      cells from small follicles was inhibited and stimulated by those from large
      follicles by indomethacin (P < 0.001), which also increased E2 output in cells
      from small follicles (P < 0.001). NO production was inhibited by both PGE2 and
      PGF2alpha except at the lowest concentration, which was stimulatory (P < 0.001).
      Indomethacin stimulated (P < 0.001) NO production. Taken together, the present
      data suggest a cross-talk between NO and PGs biosynthetic pathways, which needs
      to be further clarified.

PMID- 11577784
TI  - The effect of partial outlet obstruction on prostaglandin generation in the
      rabbit urinary bladder.
AB  - Partial outlet obstruction of the urinary bladder has been demonstrated to induce
      specific dysfunctions in cellular and sub-cellular membrane structures within the
      bladder's smooth muscle and mucosal compartments. Recent studies have linked
      these membrane dysfunctions to alterations in phospholipid metabolism leading to
      mobilization of free arachidonic acid, the precursor for synthesis of
      prostaglandins (PG). The purpose of this study was to determine if partial outlet
      obstruction of the urinary bladder induces changes in the capacity of bladder
      smooth muscle and mucosa to generate PG. PG were isolated from control and
      partially obstructed urinary bladder smooth muscle and mucosa of male New Zealand
      White (NZW) rabbits. PG concentrations (PGE2, PGF2alpha and PGI2, as its stable
      metabolite 6-keto-PGF1alpha) were determined after 30 minute incubations using
      enzyme-linked immunoassay (ELISA) kits. In both control and obstructed rabbit
      urinary bladders, PG generation was significantly higher in isolated mucosa than
      muscle tissues. A significantly higher concentration of PGF2alpha, and 6-keto
      PGF1alpha was measured in obstructed muscle tissue relative to controls. The
      concentration of 6-keto-PGF1alpha was also significantly higher than the
      concentrations measured for PGE2 and PGF2alpha in both control and obstructed
      smooth muscle samples. The generation of PGE2 was significantly higher in rabbit
      urinary bladder mucosa than either PGF2alpha or 6-keto-PGF1alpha in both control
      and obstructed samples. The capacity of obstructed mucosal tissue to generate 6
      keto-PGF1alpha was significantly higher than control tissue, while no significant
      differences in PGE or PGF2alpha generation were noted. These data suggest
      obstruction of the urinary bladder induce specific elevations in PG in both
      smooth muscle and mucosal tissues.

PMID- 11577783
TI  - A prospective randomised trial to compare the efficacy and safety of hemabate and
      syntometrine for the prevention of primary postpartum haemorrhage.
AB  - In a prospective, open-label, assessor-blind, randomised parallel group study the
      efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes,
      Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was
      compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the
      standard combination of ergometrine and syntocinon used for the active management
      of the third stage of labour and the prevention of primary postpartum haemorrhage
      (PPH). The study was set in a district general hospital with approximately 4,000
      deliveries annually. The study was discontinued at the time of the interim
      analysis because of unacceptable gastrointestinal side effects. At the time of
      the interim analysis, a total of 529 women had completed the study with 263
      randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In
      a pre-specified subgroup analysis, women delivered vaginally were further
      subdivided into those considered to be at high or low risk of primary PPH. The
      measured blood loss and incidence of PPH was similar in both treatment groups
      whether delivered by caesarean section or vaginally independent of whether women
      were considered to be at high or low risk. Adverse gastrointestinal events were
      recorded more often in the Hemabate group. The most common symptom was diarrhoea
      which occurred in 21% of women who received Hemabate compared to only 0.8% of
      Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis
      of primary PPH in all groups studied but there was a statistically significantly
      increased risk of diarrhoea among users of PGF2alpha.

PMID- 11577785
TI  - The therapeutic effect of lipo PGE1 on diabetic neuropathy-changes in endothelin
      and various angiopathic factors.
AB  - A high blood concentration of endothelin (ET)-1 may participate in the onset and
      progress of diabetic microangiopathy, resulting in neuropathy. We examined the
      therapeutic effects of prostaglandin E1 (PGE1), which possesses both a peripheral
      vasodilating action and inhibition of platelet aggregation, on diabetic
      microangiopathy. Increases in both skin temperature and peripheral never
      conduction velocity in diabetic patients were recorded four weeks after Lipo PGE1
      administration. A quantitative decrease in urinary albumin concentration was also
      observed, suggesting its efficacy of action was on diabetic nephropathy. Lipo
      PGE1 administration reduced the elevated circulating plasma ET-1 levels in the
      diabetic patients. As an increase in ET-1 concentrations is thought to correlate
      with the onset and progress of diabetic microangiopathy, the reduction of plasma
      ET-1 concentration by Lipo PGE1 administration may be one reason for the
      improvement in diabetic neuropathy and nephropathy.

PMID- 11577786
TI  - Overview of different pharmacotherapies for attaining remission in generalized
      anxiety disorder.
AB  - gamma-Aminobutyric acid (GABA), serotonin (5-HT), and norepinephrine (NE) have
      each been implicated in the putative pathophysiology of anxiety, and patients
      with generalized anxiety disorder (GAD) demonstrate dysregulation of these
      neurotransmitters. In addition, neurobiological studies have demonstrated that
      these neurotransmitter systems are extensively interrelated. As a result, drugs
      that affect serotonergic systems may also, directly or indirectly, affect other
      neurotransmitter systems including GABA and NE. In recent years, clinical
      pharmacology studies have demonstrated that pharmacotherapeutic agents that
      target more than one neurotransmitter system are more effective than agents that
      target a single system, presumably due to synergistic mechanisms. Agents that
      modulate more than one neurochemical have a broader spectrum of action and may
      facilitate the attainment of remission among patients with moderate to severe
      GAD, who are likely to have comorbid psychiatric illnesses such as depression.
      Preclinical and clinical data supporting the role of GABA, 5-HT, and NE in the
      pathophysiology of GAD are reviewed here. The pharmacotherapeutic agents that
      modulate these neurotransmitter systems and have been proved efficacious in
      reducing the symptoms associated with GAD are also summarized.

PMID- 11577787
TI  - Optimizing pharmacotherapy of generalized anxiety disorder to achieve remission.
AB  - More than half of patients with generalized anxiety disorder (GAD) have chronic
      and persistent symptomatology that may warrant ongoing pharmacotherapy. Many of
      these patients also have significant comorbid mood and anxiety disorders. There
      is growing consensus among clinicians that the treatment goal for anxiety
      disorders should be remission, including the minimization of anxiety and
      depression and resolution of functional impairment. Clinical management
      strategies for optimizing pharmacotherapy aimed at achieving remission in GAD
      include attention to drug selection, dosing levels, and duration of treatment. To
      optimize treatment for GAD with the goal of achieving remission, it is reasonable
      to select an agent with demonstrated effectiveness for GAD and associated
      comorbidities as well as a favorable side effect profile. Dosing and duration of
      treatment should be adequate, and consideration of adjunctive strategies for
      refractory patients may be warranted. This article discusses the optimization of
      pharmacotherapy with the goal of promoting remission in patients with GAD.

PMID- 11577788
TI  - Attaining remission in generalized anxiety disorder: venlafaxine extended release
      comparative data.
AB  - Generalized anxiety disorder (GAD) is a chronic mental disorder that is
      characterized by excessive anxiety or worry. Traditionally, the treatment goal
      for GAD has been the attainment of a treatment response, clinically defined as a
      40% to 50% symptomatic improvement relative to baseline. However, there is
      growing consensus among clinical psychiatrists that the treatment goal should be
      remission, a virtually asymptomatic state that corresponds to a score of < or = 7
      on the Hamilton Rating Scale for Anxiety (HAM-A) or a > or = 70% symptomatic
      improvement from baseline. Venlafaxine extended release (XR), a serotonin
      norepinephrine reuptake inhibitor, is the first pharmacotherapeutic agent to be
      indicated for both depression and GAD. This article reviews the efficacy data
      from several short- and long-term placebo-controlled studies of venlafaxine
      conducted to evaluate the potential of this agent to facilitate remission. Total
      scores on the HAM-A and the Clinical Global Impressions scale were used as the
      primary variables; scores for the HAM-A psychic and somatic anxiety factors and
      for the Hospital Anxiety and Depression scale were used as secondary variables.
      Venlafaxine XR showed a substantial effect size in the individual HAM-A items of
      worry, anxiety, and behavior at interview. The pooled analysis of 2 long-term
      studies indicated that the scores of venlafaxine remitters separated from those
      of responders by the second month, resulting in an overall increase in remitters.
      The results of these studies demonstrate the strong potential of venlafaxine XR
      in facilitating remission in GAD.

PMID- 11577789
TI  - Sensitizing clinicians and patients to the social and functional aspects of
      remission.
AB  - Axis I disorders are defined by specific symptom constellations that are
      frequently accompanied by notable impairments in social functioning. Social role
      impairments diminish personal fulfillment, satisfaction, and quality of life. It
      is now clear that these findings suggest a broader definition of remission that
      involves not only the absence of symptoms but also improvement in psychosocial
      functioning. Clinicians and patients need to become sensitized to the role of
      social functioning and quality of life in the assessment of treatment outcomes.
      Although there has been a recent emphasis on the inclusion of social function and
      quality of life measures in the definition of and requirements for remission,
      numerous standardized scales for measuring these factors already exist. In
      addition, selection of efficacious therapeutic agents proven to promote both
      elimination of symptoms and return to full social functioning is important.
      Finally, significant improvement in both symptoms and function may be necessary
      to prevent not only relapse but also ensure full remission of anxiety and
      depressive disorders.

PMID- 11577790
TI  - Dissolving the burden of generalized anxiety disorder.
AB  - Generalized anxiety disorder (GAD) is a common disorder marked by excessive
      anxiety, worry, and somatic manifestations lasting over 6 months. GAD occurs
      relatively early in life in the majority of individuals; it is often chronic and
      comorbid with other anxiety disorders, affective disorders, and/ or medical
      conditions. GAD is as functionally debilitating as major depression even without
      comorbidity and, hence, is associated with considerable economic and societal
      burdens as well as health care utilization. Underrecognition of GAD and
      undertreatment of this disorder are major factors contributing to the individual
      and societal burden of GAD. Earlier long-term studies in GAD reported low
      remission rates despite treatment. More recent data support the potential for
      achieving remission in GAD with appropriate treatment. There is a critical need
      to enhance mental health literacy programs and translate the efficacy data into
      effectiveness schemes in clinical practice by improving disease management
      strategies. A conceptual basis for achieving these goals is provided by moving
      from a disorder model to a disease model in psychiatric practice. This move
      allows for staging of psychiatric illnesses, with GAD as a prototypical example.
      For the clinician, the critical paradigm shift is in modifying the treatment goal
      from the attenuation of symptoms, as in a "response," to the achievement of a
      state of "remission" (i.e., a virtually asymptomatic state). Remission of
      symptoms allows for improvement of psychosocial functioning and quality of life
      and potentially wellness. In this review, a synopsis of the epidemiology, natural
      history, economic and social cost, and clinical management issues is given as a
      road map to dissolving the burden of GAD.

PMID- 11577791
TI  - Should inhaled corticosteroids be used in the long term treatment of chronic
      obstructive pulmonary disease?
AB  - Chronic obstructive pulmonary disease (COPD) is a progressive disease with
      alveolar destruction (emphysema) and bronchiolar fibrosis (obstructive
      bronchitis) in variable proportions. Reducing disease progression, as assessed by
      forced expiratory volume in I second (FEV1) decline, health-related quality of
      life, exacerbation rate and mortality, is a more realistic outcome than
      physiological improvement. This paper reviews all the published studies of at
      least 100 patients followed for at least 2 years. Studies have included patients
      with mild COPD (Copenhagen City Lung Study) to advanced symptomatic disease
      [Inhaled Steroids in Obstructive Lung Disease (ISOLDE)], with 2 studies of those
      with relatively early symptoms [European Respiratory Society Study on Chronic
      Obstructive Pulmonary Disease (EUROSCOP) and Lung Health-21. Exacerbation
      frequency, and probably severity, are reduced by high dose inhaled
      corticosteroids. Exacerbations are only frequent in more advanced disease,
      limiting the use of this outcome in EUROSCOP and Lung Health-2. Exacerbations are
      associated with reduced health-related quality of life. ISOLDE clearly showed a
      reduced rate in decline of the disease-specific St George's Respiratory
      Questionnaire with fluticasone propionate, partly related to the reduced
      exacerbations. The symptom component of the score showed the greatest difference
      between placebo and fluticasone propionate. None of the larger studies were able
      to reproduce the statistically significant reduction in the rate of decline in
      FEV1 suggested by the smaller, earlier studies. This might at least in part be as
      a result of the statistical modelling used which cannot adequately compensate for
      those with more rapidly progressive disease dropping out earlier. The equivalent
      doses of inhaled corticosteroids differed approximately fivefold between the
      major studies. The more positive results were obtained with higher doses.
      Oropharyngeal adverse effects were similar to those seen in patients with asthma;
      bruising was increased in one study with budesonide, otherwise adverse effects
      were similar to placebo. Bone loss was specifically studied in subgroups of
      patients in EUROSCOP and Lung Health-2. Budesonide 800 microg/day was associated
      with less bone loss than placebo, whereas triamcinolone 1200 microg/day was
      associated with excess bone loss. High dose inhaled corticosteroids have a
      favourable risk/benefit ratio in patients with advanced disease, particularly
      those with frequent exacerbations, and no benefit for those with very mild
      disease. It is not possible from the data to make firm recommendations for the
      important intermediate group where delaying progression is likely to lead to
      greatest benefit. I believe high dose inhaled steroids are warranted for those
      with intermediate severity COPD, who have frequent exacerbations or significant
      COPD-related symptoms.

PMID- 11577792
TI  - Recent advances in the treatment of gastric cancer.
AB  - Gastric cancer is one of the most common cancers in the world. The prognosis of
      the disease is poor, with only 40% of patients eligible to undergo potentially
      curative surgery. Even for those patients who undergo a complete resection, the
      rate of recurrence is very high. Extensive studies of multidisciplinary adjuvant
      treatment have been conducted seeking to improve the cure rates in the past two
      decades. The benefit of D2 dissection is still controversial and is undergoing
      prospective evaluation. Preliminary results from the United States
      Gastrointestinal Intergroup study, a well designed trial, have shown overall
      survival benefit of postoperative chemoradiation therapy. Neoadjuvant
      chemotherapy or chemoradiation is under active study in order to increase the
      number of patients to undergo potential curative surgery. Although many
      chemotherapy regimens have been developed recently, only modest clinical efficacy
      has been demonstrated for advanced metastatic disease. So far, there is no single
      regimen considered to be standard.

PMID- 11577793
TI  - Anti-emetics for cancer chemotherapy-induced emesis: Potential of alternative
      delivery systems.
AB  - Currently, the most commonly used routes of administration of antiemetics in
      chemotherapeutic regimens are oral and intravenous. Patient compliance and thus
      efficacy of conventional drug schedules and formulations are often impaired by
      difficulties associated with oral or intravenous uptake of the administered
      chemotherapy. Alternative or new drug delivery systems should overcome these
      problems by improving patient compliance. Several new drug delivery systems are
      available and development of these new systems is ongoing, in particular to meet
      delivery requirements of modern biological therapeutics and the application of
      gene therapy. However, at the present time, the implementation of new techniques
      of alternative antiemetic drug administration for chemotherapy-induced emesis is
      very limited. The challenge for clinical investigations to further develop new
      delivery systems, in particular for antiemetic therapies, remains.

PMID- 11577795
TI  - Optimising outcomes in acute pancreatitis.
AB  - Acute pancreatitis is a common cause for presentation to emergency departments.
      Common causes in Western societies include biliary pancreatitis and alcohol (the
      latter in the setting of chronic pancreatitis). Acute pancreatitis also follows
      endoscopic retrograde pancreatography in 5 to 10% of patients, a group that could
      potentially benefit from prophylactic treatment. Although episodes of
      pancreatitis usually run a relatively benign course, up to 20% of patients have
      more severe disease, and this group has significant morbidity and mortality.
      Therefore, attempts have been made to identify, at or soon after presentation,
      those patients likely to have a poor outcome and to channel resources to this
      group. The mainstay of treatment is aggressive support and monitoring of those
      patients likely to have a poor outcome. Pharmacotherapy for acute pancreatitis
      (both prophylactic and in the acute setting) has been generally disappointing.
      Efforts initially focused on protease inhibitors, of which gabexate shows some
      promise as a prophylactic agent. Agents that suppress pancreatic secretion have
      produced disappointing results in human studies. Infection of pancreatic necrosis
      is associated with high mortality and requires surgical intervention. In view of
      the seriousness of infected necrosis, the use of prophylactic antibacterials such
      as carbapenems and quinolones has been advocated in the setting of pancreatic
      necrosis. Similarly, data are accumulating to support the use of prophylactic
      antifungal therapy. Recently, it has become apparent that the intense
      inflammatory response associated with acute pancreatitis is responsible for much
      of the local and systemic damage. With this realisation, future efforts in
      pharmacotherapy are likely to focus on suppression or antagonism of pro
      inflammatory cytokines and other inflammatory mediators. Similarly, animal
      studies have demonstrated the importance of oxidative stress in acute
      pancreatitis, although to date there is a paucity of information regarding the
      efficacy of antioxidants. Although the clinical course for most patients with
      acute pancreatitis is mild, severe acute pancreatitis continues to be a clinical
      challenge, requiring a multidisciplinary approach of physician, intensivist and
      surgeon.

PMID- 11577796
TI  - Management of scalp psoriasis: guidelines for corticosteroid use in combination
      treatment.
AB  - Scalp psoriasis is a frequent expression of the common skin disease psoriasis,
      and scaling and itching are the two major complaints. Topical treatments are the
      mainstay of the treatment of psoriasis of the scalp, with the vehicle as well as
      the active ingredient relevant to efficacy, tolerability and compliance. Vehicles
      can be shampoos, lotions, gels, foams, creams and more greasy ointments. Active
      ingredients are keratolytics, coal tar (liquor carbonis detergens), dithranol,
      corticosteroids and vitamin D3 analogues. Some effect has also been described
      from topical or systemic imidazole derivatives. Topical corticosteroids remain
      the mainstay in the treatment of scalp psoriasis. The effects are rapid, the
      formulations are patient friendly and the adverse effects seem limited, although
      no data are available to support safety during prolonged use (more than 4 weeks).
      Topical vitamin D3 analogues have been available for the treatment of psoriasis
      since 1992. In the lotion formulation in particular, vitamin D3 analogues are a
      patient friendly, tolerable and effective alternative to corticosteroids,
      although the effects are optimal after 8 weeks, in contrast to 2-3 weeks for
      topical corticosteroids. Facial irritation (often temporary) can also be a
      disadvantage of vitamin D3 analogues, although only a small proportion of
      patients stop treatment for this reason. All other treatment options for
      psoriasis, such as tazarotene, phototherapy and systemic treatment with
      methotrexate, acitretin and cyclosporin are often not indicated or not suitable
      for treatment of the scalp. In daily practice, to make a choice from the
      available therapeutic arsenal for psoriasis, each patient should be examined
      individually. Deteriorating factors have to be excluded. For scaling, keratolysis
      is the first step. Subsequently, active treatment can be chosen depending on the
      clinical picture. When the psoriatic lesions are mainly characterised by
      inflammation, anti-inflammatory drugs such as topical corticosteroids are
      indicated. When scaling is the more important clinical feature, vitamin D3
      analogues are indicated. Generally, intermittently used topical corticosteroids
      alternating with vitamin D3 derivatives either combined or not with liquor
      carbonis detergens containing shampoo is the most suitable treatment for most
      patients. Because psoriasis capitis is a chronic disease, long term treatment
      should, in addition to medical advice, also provide patient support and
      motivation.

PMID- 11577797
TI  - Insulin glargine: a review of its therapeutic use as a long-acting agent for the
      management of type 1 and 2 diabetes mellitus.
AB  - Insulin glargine is a recombinant human insulin analogue produced by DNA
      technology using a nonpathogenic strain of Escherichia coli. Two modifications of
      human insulin result in a stable molecule which is soluble in slightly acidic
      conditions (pH 4.0) and precipitates in the neutral pH of subcutaneous tissue.
      Because of these properties, absorption of insulin glargine is delayed and the
      analogue provides a fairly constant, basal insulin supply without peaks in plasma
      insulin levels for approximately 24 hours, similar to that achieved by a
      continuous subcutaneous insulin infusion. Insulin glargine is indicated as a once
      daily subcutaneous injection to provide basal glycaemic control in adults and
      children aged >6 years with type 1 diabetes mellitus and in adults with type 2
      diabetes mellitus. Fasting plasma glucose and fasting blood glucose levels
      generally improved to a greater extent in patients with type 1 diabetes mellitus
      receiving insulin glargine than patients who administered Neutral Protamine
      Hagedorn (NPH) insulin. In patients with type 1 or 2 disease, glycosylated
      haemoglobin levels were slightly reduced and to a similar extent with insulin
      glargine and NPH insulin. Most clinical trials in patients with type 1 or 2
      diabetes mellitus demonstrated a lower incidence of hypoglycaemia, especially
      nocturnal hypoglycaemia, compared with NPH insulin. One of the most common
      adverse events with insulin glargine treatment was injection site pain which, in
      some studies, occurred more frequently than in patients receiving NPH insulin. In
      all cases the symptoms were mild and treatment discontinuation was not required.
      Otherwise, the drug is well tolerated and does not appear to be immunogenic.
      CONCLUSIONS: Insulin glargine once a day provides basal control of glycaemia for
      approximately 24 hours without inducing peaks in plasma insulin levels in
      patients with type 1 or 2 diabetes mellitus. In long term, well designed trials
      insulin glargine once daily improved glycaemic control at least as effectively as
      NPH insulin given once or twice daily. The drug was well tolerated and in most
      studies the incidence of nocturnal hypoglycaemia was significantly less in
      patients treated with insulin glargine compared with patients receiving NPH
      insulin. Therefore, insulin glargine is likely to be a useful addition to the
      armamentarium of insulin therapy by establishing basal glycaemic control with
      once daily administration and a reduced risk of nocturnal hypoglycaemia.

PMID- 11577794
TI  - Intranasal corticosteroids for allergic rhinitis: superior relief?
AB  - Whether first-line pharmacological treatment of allergic rhinitis should be
      antihistamines or intranasal corticosteroids has been discussed for several
      years. First-generation antihistamines are rarely used in the treatment of
      allergic rhinitis, mainly because of sedative and anticholinergic adverse
      effects. On the basis of clinical evidence of efficacy, no second-generation
      antihistamine seems preferable to another. Similarly, comparisons of topical and
      oral antihistamines have been unable to demonstrate superior efficacy for one
      method of administration over the other. Current data documents no striking
      differences in efficacy and safety parameters between intranasal corticosteroids.
      When the efficacy of antihistamines and intranasal corticosteroids are compared
      in patients with allergic rhinitis, present data favours intranasal
      corticosteroids. Interestingly, data do not show antihistamines as superior for
      the treatment of conjunctivitis. Safety data from comparative studies in patients
      with allergic rhinitis do not indicate differences between antihistamines and
      intranasal corticosteroids. Combining antihistamines and intranasal
      corticosteroids in the treatment of allergic rhinitis does not provide any
      additional effect to intranasal corticosteroids alone. On the basis of current
      data, intranasal corticosteroids seem to offer superior relief in allergic
      rhinitis than antihistamines.

PMID- 11577800
TI  - Acetylcholinesterase inhibition and the extrapyramidal syndrome: a review of the
      neurotoxicity of organophosphate.
AB  - Organophosphate poisonings are not uncommon, and are the leading cause of death
      in suicide patients in Taiwan. Acute cholinergic crisis caused by the inhibition
      of synaptic acetylcholinesterase is the major manifestation of organophosphate
      poisoning and may cause death within minutes. Delayed neurotoxicities include
      intermediate syndrome and delayed polyneuropathy have also been described.
      However, these symptoms may not characterize the complete picture of
      organophosphate poisoning. Among the 633 patients ever admitted to our hospital
      with organophosphate poisoning, three patients were found exhibiting impermanent
      neuromuscular dysfunction, including blepharoclonus, oculogyric crisis,
      intermittent dystonia, rigidity, and tremor, with two of them developing mask
      face, dyskinesia and akathisia later, following acute cholinergic crisis. The
      symptoms appeared within 4 days with the duration ranging from 25 days to 2
      months. Other causes of the extrapyramidal syndrome noted on these patients have
      been excluded, and we consider the extrapyramidal syndrome a possible neurotoxic
      manifestation of organophosphate poisoning, which is transient, needs no
      treatment, and may be missed because of the critical condition, in a minority of
      patients. The mechanism remains to be identified, but may be related to the
      impediment of the function of acetylcholinesterase to modify nigrostriatal
      dopaminergic system, which is independent of hydrolyzing acetylcholine. More
      detailed observation for organophosphate poisoned patients and more studies for
      the biological functions of acetylcholinesterase including the influence on the
      nigrostriatal dopaminergic system are needed.

PMID- 11577798
TI  - Repaglinide: a review of its therapeutic use in type 2 diabetes mellitus.
AB  - Repaglinide, a carbamoylmethyl benzoic acid derivative, is the first of a new
      class of oral antidiabetic agents designed to normalise postprandial glucose
      excursions in patients with type 2 diabetes mellitus. Like the sulphonylureas,
      repaglinide reduces blood glucose by stimulating insulin release from pancreatic
      beta-cells, but differs from these and other antidiabetic agents in its
      structure, binding profile, duration of action and mode of excretion. In clinical
      trials of up to 1-year's duration, repaglinide maintained or improved glycaemic
      control in patients with type 2 diabetes mellitus. In comparative, 1-year, double
      blind, randomised trials (n = 256 to 544), patients receiving repaglinide (0.5 to
      4mg before 3 daily meals) achieved similar glycaemic control to that in patients
      receiving glibenclamide (glyburide) < or = 15 mg/day and greater control than
      patients receiving glipizide < or = 15 mg/day. Changes from baseline in
      glycosylated haemoglobin and fasting blood glucose levels were similar between
      patients receiving repaglinide and glibenclamide in all studies; however,
      repaglinide was slightly better than glibenclamide in reducing postprandial blood
      glucose in I short term study (n = 192). Patients can vary their meal timetable
      with repaglinide: the glucose-lowering efficacy of repaglinide was similar for
      patients consuming 2, 3 or 4 meals a day. Repaglinide showed additive effects
      when used in combination with other oral antidiabetic agents including metformin,
      troglitazone, rosiglitazone and pioglitazone, and intermediate-acting insulin
      (NPH) given at bedtime. In 1-year trials, the most common adverse events reported
      in repaglinide recipients (n = 1,228) were hypoglycaemia (16%), upper respiratory
      tract infection (10%), rhinitis (7%), bronchitis (6%) and headache (9%). The
      overall incidence of hypoglycaemia was similar to that recorded in patients
      receiving glibenclamide, glipizide or gliclazide (n = 597) [18%]; however, the
      incidence of serious hypoglycaemia appears to be slightly higher in sulphonylurea
      recipients. Unlike glibenclamide, the risk of hypoglycaemia in patients receiving
      repaglinide was not increased when a meal was missed in 1 trial. In conclusion,
      repaglinide is a useful addition to the other currently available treatments for
      type 2 diabetes mellitus. Preprandial repaglinide has displayed
      antihyperglycaemic efficacy at least equal to that of various sulphonylureas and
      is associated with a reduced risk of serious hypoglycaemia. It is well tolerated
      in a wide range of patients, including the elderly, even if a meal is missed.
      Furthermore, glycaemic control is improved when repaglinide is used in
      combination with metformin. Thus, repaglinide should be considered for use in any
      patient with type 2 diabetes mellitus whose blood glucose cannot be controlled by
      diet or exercise alone, or as an adjunct in patients whose glucose levels are
      inadequately controlled on metformin alone.

PMID- 11577799
TI  - Interferon alfacon-1: a review of its pharmacology and therapeutic efficacy in
      the treatment of chronic hepatitis C.
AB  - Interferon alfacon-1 (consensus interferon) is a non-naturally occurring,
      synthetic, type 1 interferon (IFN)alpha that is used for the treatment of
      patients with chronic hepatitis C. The efficacy of subcutaneously administered
      interferon alfacon-1 has been demonstrated in clinical trials during the
      treatment of LFN-naive patients (interferon alfacon-1 9microg 3 times a week for
      24 weeks) and retreatment of nonresponders and relapsers to previous interferon
      therapy (interferon alfacon1 15 microg 3 times a week for up to 48 weeks). Higher
      and more frequent interferon alfacon-1 dosages have also been investigated.
      Results from a pivotal double-blind randomised trial in 704 patients with chronic
      hepatitis C showed that interferon alfacon-19 microg 3 times a week achieved
      virological and biochemical response rates of 34.9 and 42.2%, respectively, at
      treatment end-point (week 24). Sustained virological and biochemical responses
      (week 48) were reported in 12.1 and 20.3% of the patients, respectively. In
      general, response rates in recipients of interferon alfacon-1 9 microg 3 times a
      week were similar to those achieved with IFN-alpha2b 3 MIU 3 times a week.
      However, interferon alfacon-1 was more effective in the subgroup of patients
      infected with hepatitis C virus (HCV) genotype 1 at end-point (virological
      response, 24 vs 15%; p < 0.05) and post-treatment observation period (8 vs 4%)
      although the difference between treatment groups was statistically significant
      only at treatment end-point. The sustained virological response rate achieved in
      patients with high baseline levels of serum HCV RNA receiving interferon alfacon
      1 was statistically superior to that exhibited in the IFN-alpha2b treatment group
      (7 vs 0%; p < Interferon alfacon-1 also showed efficacy during the retreatment of
      non-responders and relapsers to previous IFN therapy in a large nonblind
      multicentre trial. Sustained virological response (week 72) was observed among 13
      and 58% of nonresponders and relapsers, respectively, after 48 weeks of treatment
      with interferon alfacon-1 15 microg 3 times a week. Interferon alfacon-1 has been
      generally well tolerated in clinical trials. As with other IFNs, adverse events
      were reported frequently but were usually considered of mild to moderate
      severity, decreased with time and caused a small percentage of patients to
      withdraw from the treatment. Fever, fatigue, arthralgia, myalgia, headache and
      rigors were the most frequently reported adverse events. Psychiatric adverse
      events appeared to be dose-related and caused the majority of treatment
      withdrawals. CONCLUSION: Interferon alfacon-1 is generally well tolerated and is
      an effective agent in the treatment of patients with chronic hepatitis C.
      Comparative data from a pivotal randomised trial indicate that the drug has at
      least equivalent efficacy to IFNalpha-2b, and a statistically significant
      advantage was demonstrated at treatment end-point in patients infected with HCV
      genotype 1. A number of ongoing trials with interferon alfacon-1 are evaluating
      issues such as the optimal dosage regimen and duration of therapy in an effort to
      improve sustained virological response to therapy, a goal for IFNs in general.

PMID- 11577801
TI  - Lead alters the developmental profile of the galactolipid metabolic enzymes in
      cultured oligodendrocyte lineage cells.
AB  - Lead is a neurotoxicant that can cause myelin deficits. Galactolipids are
      expressed during differentiation of oligodendrocyte lineage cells and accumulate
      in myelin. To examine the impact of lead on oligodendroglial differentiation,
      galactolipid metabolism in cultured oligodendrocyte lineage cells exposed to the
      metal was studied. Oligodendrocyte progenitor cells obtained from newborn rat
      pups were exposed to 1 microM lead acetate for 24 h prior to maintenance of the
      cells in medium containing the metal salt for 0, 2, or 6 days of differentiation.
      Lead caused approximately 50% reduction in levels of the galactolipid
      biosynthetic transferases, UDP-galactose:ceramide galactosyltransferase and 3'
      phosphoadenosine-5'-phosphosulfate:galactocerebroside sulfotransferase, as
      compared to sodium-treated controls, in cultures of oligodendrocyte lineage cells
      following 2 days of differentiation. The activities of the galactolipid catabolic
      hydrolases, galactocerebroside-beta-galactosidase and arylsulfatase A, were
      reduced by 20%. Following 6 days of differentiation, lead-exposed cells exhibited
      levels of all the enzymes, except for arylsulfatase A, similar to those of the
      control cells. These results are consistent with the lead-induced delay of
      oligodendrocyte differentiation, as evidenced by the emergence of stage-specific
      immunochemical markers and the observed change in the developmental activity
      profile of 2',3'-cyclic nucleotide 3'-phosphohydrolase. The activity of
      arylsulfatase A in lead-treated 6-day oligodendrocytes was significantly less
      than that found in control cultures. This effect is consistent with the lead
      induced reduction of arylsulfatase A in human fibroblasts caused by mis-sorting
      the newly-synthesized enzyme. The perturbation of galactolipid metabolism by lead
      during developmental maturation of oligodendrocytes may represent a contributing
      mechanism for lead-induced neurotoxicity.

PMID- 11577802
TI  - Spatial distribution of EEG theta activity as a function of lifetime lead
      exposure in 9-year-old children.
AB  - The relationship between low-level childhood lead exposure and developmental
      retardation has been proposed but the existing evidence is weak. We examined the
      EEG of 42 children participating in the Mexico City Prospective Lead Study to
      determine if relative theta power and distribution across the scalp was related
      to history of lifetime lead exposure as measured by sequential blood lead
      concentration of the mother during pregnancy and the child after delivery. EEG
      was recorded from scalp electrodes placed according to the 10-20 system during
      eyes-closed. Theta activity (4-7 Hz) was filtered with a fast Fourier transform
      (FFT) and relative power calculated. The expected distribution of theta was
      found, with the greatest relative power centrally located and lesser amounts at
      frontal, occipital, and lateral derivations. Multiple regression models of theta
      at each electrode showed that increasing postnatal blood lead from 6 to 96 months
      was related to increasing relative theta power adjusted for age, sex and fetal
      suffering at delivery, in occipital derivations. The most significant increases
      in theta power were associated with blood lead levels (geometric mean = 10.3
      microg/dl) measured between 54 and 72 months. Spatially weighted regression
      demonstrated that there was a significant antero-posterior gradient in lead
      induced increase in relative theta power associated with postnatal blood lead
      levels at 54-72 months and 78-96 months. The greatest lead effect on both
      occipital relative theta power and the antero-posterior gradient of theta power
      was found with lead at an age during which relative theta power reaches its
      developmental maximum and starts to decrease. Results suggest that 54-72 months
      represent a critical period during which lead can exert lasting effects on the
      developmental pattern of theta activity. Occipital derivation of the largest
      effects of lead on theta activity may also be related to other lead-related
      developmental deficits.

PMID- 11577803
TI  - Clostridium botulinum neurotoxins act with a wide range of potencies on SH-SY5Y
      human neuroblastoma cells.
AB  - We have described, in undifferentiated SH-SY5Y human neuroblastoma cells, the
      relative potency of Clostridium botulinum neurotoxin (BoNT) serotypes A-F
      Sensitivity of stimulated [3H]-noradrenaline ([3H]-NA) release to the toxins had
      a rank order of potency of: C > D > A > B > F after 3 days exposure. The
      difference between the most potent (BoNT/C: IC50 0.54 nM) and the least (BoNT/F:
      IC50 > 300 nM) was approximately 1,000-fold. Though fluid phase endocytosis may
      have been the mechanism of entry for low potency toxins the far higher potency of
      BoNT/C would suggest receptor-driven entry. Potency was not a reflection of the
      dependence of the release mechanism on a particular SNARE since the substrate
      specificities were mixed throughout the potency order. This indicated that the
      toxins differed in their efficiency of binding/endocytosis or enzymatic activity
      inside the cell. The serotypes that cleaved vesicle-associated membrane protein
      (VAMP) isoforms (BoNT/B, D and F) did not fully inhibit [3H]-NA release. Cleavage
      of the appropriate substrate proteins was observed for all serotypes. SNAP-25
      cleavage by BoNT/A was shown to be a dose-dependent and correlated closely with
      reduction of release, supporting proteolysis as the mechanism by which toxin
      inhibited secretion. Comparison of the SH-SY5Y cell line sensitivity to BoNT/A
      with glycine releasing rat primary spinal cord neuron cultures, revealed a
      massive difference in potency; the primary cultures being approximately 200,000
      fold more sensitive. The demonstration, using BoNTs, of the crucial role of SNAP
      25, VAMP and syntaxin in SH-SY5Y cells suggests the use of this neuroblastoma as
      a model in the study of these proteins in neurotransmitter release.

PMID- 11577804
TI  - Does trimetazidine exert cytoprotective activity on astrocytes subjected to
      hypoxia in vitro?
AB  - The aim of the present study was to establish whether trimetazidine (TMZ) is
      capable of protecting astrocytes against hypoxic injury. Using the model of
      astrocyte cell culture we tried to observe the cells treated with TMZ before,
      during and after hypoxia simulated in vitro. Cell viability was determined by
      Live/Dead (viability/cytotoxicity) Assay Kit and MTT conversion test. Apoptotic
      cell death was distinguished by a method using fluorescence microscopy with
      Hoechst 33342. The effect of the drug on the DNA synthesis was evaluated by
      measuring the incorporation of [3H]thymidine into DNA of astrocytes. TMZ
      stimulates the proliferation of astrocytes most significant one when the
      astrocytes are exposed to the drug in normoxia, hypoxia and/or re-oxygenation.
      Adding TMZ into cultures during re-oxygenation and hypoxial re-oxygenation
      significantly decreases the number of dead and apoptotic cells. Our experiment
      has proved that TMZ exerts the most significantly cytoprotective effect on
      astrocytes in vitro when added during hypoxia and/or re-oxygenation. We may
      conclude that the protective effect of TMZ depends on the sequence of drug adding
      and hypoxia/ re-oxygenation onset.

PMID- 11577805
TI  - Serum dioxin and peripheral neuropathy in veterans of Operation Ranch Hand.
AB  - We studied whether exposure to Agent Orange and its contaminant, 2,3,7,8
      tetrachlorodibenzo-p-dioxin (dioxin), during the Vietnam War is related to
      peripheral neuropathy. The index subjects were veterans of Operation Ranch Hand,
      the unit responsible for aerial herbicide spraying in Vietnam from 1962 to 1971.
      We report peripheral nerve function assessed in 1982, 1985, 1987, 1992 and 1997,
      nerve conduction velocities measured in 1982, and vibrotactile thresholds of the
      great toes measured in 1992 and 1997. We assigned each Ranch Hand veteran to one
      of three exposure categories named "background", "low" and "high", based on his
      serum dioxin level. Other than the bilateral vibrotactile abnormalities, we
      consistently found a statistically significant increased risk of all indices of
      peripheral neuropathy among Ranch Hand veterans in the high exposure category in
      1997, and a statistically significant increased risk of diagnosed peripheral
      neuropathy, incorporating bilateral vibrotactile abnormalities of the great toes,
      in the high category in 1992. Restricting to the enlisted veterans did not alter
      these results. Cautious interpretation of these results is appropriate until the
      relationship between pre-clinical diabetes mellitus and peripheral neuropathy is
      further evaluated in future examinations.

PMID- 11577807
TI  - Severe abdominal infections in neutropenic patients.
AB  - Abdominal infections are an important cause of morbidity and mortality in
      neutropenic patients. We present a retrospective series of 16 patients, mostly
      with acute leukemia, who developed severe abdominal infections during
      chemotherapy-induced neutropenia between 1991 and 1997. The frequency among
      patients with acute leukemia was 2.35% (13 of 553). Thirteen patients presented
      with enterocolitis and 3 patients presented with cholecystitis. Eight patients
      died. Bacteremia was present in 6 patients, 4 patients suffered from proven or
      strongly suspected fungal infections, and 1 patient suffered from cytomegalovirus
      infection. Early surgical management was required in a patient with intestinal
      obstruction, whereas other patients could be managed conservatively. Two patients
      with acute cholecystitis were treated with antibiotics until the end of
      neutropenia and then were resected. Severe abdominal injections in neutropenic
      patients, which are often fatal, were caused by nonbacterial microorganisms in
      one-fourth of the cases and could be managed conservatively in most instances.

PMID- 11577806
TI  - Serum dioxin and cognitive functioning among veterans of Operation Ranch Hand.
AB  - We used the Halstead-Reitan neuropsychological test battery, the Wechsler adult
      intelligence scale-revised, the Wechsler memory scale, and the wide range
      achievement test to assess cognitive functioning among Air Force veterans exposed
      to Agent Orange and its contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (dioxin), during the Vietnam war The index subjects were veterans of Operation
      Ranch Hand (N = 937), the unit responsible for aerial herbicide spraying in
      Vietnam from 1962 to 1971. A comparison group of other Air Force veterans (N=
      1,052), who served in Southeast Asia during the same period but were not involved
      with spraying herbicides served as referents. Cognitive functioning was assessed
      in 1982, and dioxin levels were measured in 1987 and 1992. We assigned each Ranch
      Hand veteran to the background, low, or high dioxin exposure category on the
      basis of a measurement of dioxin body burden. Although we found no global effect
      of dioxin exposure on cognitive functioning, we did find that several measures of
      memory functioning were decreased among veterans with the highest dioxin
      exposure. These results became more distinct when we restricted the analysis to
      enlisted personnel, the subgroup with the highest dioxin levels. An analysis
      based on dioxin quintiles in the combined cohort produced consistent results,
      with veterans in the fifth quintile exhibiting reduced verbal memory function.
      Although statistically significant, these differences were relatively small and
      of uncertain clinical significance.

PMID- 11577808
TI  - Detection of c-erbB-2 gene amplification in cervical scrapes positive for human
      papillomavirus (HPV).
AB  - c-erbB-2 gene amplification has been described in a variety of human cancers, but
      it has been poorly studied in noncancerous cytological samples from genital
      specimens positive for human papillomavirus (HPV). Furthermore, the relationship
      between this genetic event and the presence of high-risk and low-risk HPV types
      is poorly studied. Eighty-four noncancerous cytological samples from exocervical
      specimens that were positive for HPV types 6, 16, and 18 were analyzed for c-erbB
      2 gene amplification using the genomic differential polymerase chain reaction
      with the single copy reference gene. An association between c-erbB-2 gene
      amplification and the group corresponding to HPV type 6 was found. Within the low
      risk HPV group, c-erbB-2 amplification was associated to cervical intraepithelial
      neoplasia of grade I (CIN I). Because in the samples analyzed, most of the CIN I
      stage was characterized by a koilocytotic pattern, c-erbB-2 amplification could
      be related to this kind of cellular alteration. It would be important to study c
      erbB-2 gene amplification and also gene expression in different CIN stages in
      order to determine its role and significance in cervical cancer.

PMID- 11577809
TI  - Health literacy and shared decision making for prostate cancer patients with low
      socioeconomic status.
AB  - Quality of life (QOL) considerations are important in the treatment decision
      making process for prostate cancer patients. Although patient involvement in the
      treatment decision process has been encouraged, low health literacy can limit
      patient understanding of the complex information about treatments and their
      probable QOL outcomes and is a barrier to patient participation in the decision
      making process. The objectives of the study were to evaluate (i) knowledge, level
      of satisfaction, and treatment preferences and intentions of men newly diagnosed
      with prostate cancer after participation in a CD-ROM shared decision making
      program; and (ii) the relationship between prostate cancer knowledge and health
      literacy. Thirty newly diagnosed prostate cancer patients from two Veteran's
      Administration (VA) hospitals in Chicago completed a demographic questionnaire
      and participated in an interactive CD-ROM shared decision making program.
      Subsequently, knowledge of prostate cancer, satisfaction with the information in
      the computer CD-ROM program, treatment preferences, and likelihood of following
      treatment preferences were assessed using interviewer-administered
      questionnaires. Health literacy was assessed using the Rapid Estimate of Adult
      Literacy in Medicine (REALM). The Pearson correlation test was used to assess the
      relationship between health literacy and prostate cancer knowledge. The chi2 test
      and the Fischer exact test were used to evaluate relationships between patient
      demographics and other variables. More than three-quarters of the patients rated
      the information in the CD-ROM as "very satisfactory" (highest possible rating).
      Two-thirds of the patients (21 of 30) selected a treatment after participation in
      the CD-ROM program and 90.5% of these patients stated that they were very or
      somewhat likely to adhere to their selection. However, prostate cancer knowledge
      was variable, with one-third of the patients scoring 69.9% or lower.
      Participants' health literacy was equivalent to a 7th-8th grade reading level
      (mean = 57.1+/-10.9), and more than one-third of participants (36.7%) had lower
      than 9th grade literacy levels. Participants' prostate cancer knowledge was
      correlated with health literacy (Pearson correlation rhor = 0.65, rhop = 0.0001).
      Patients were satisfied with the interactive shared decision making CD-ROM
      program, and two-thirds of patients were able to select a preferred treatment
      based on the information presented in the program that they intended to follow.
      However, prostate cancer knowledge scores varied among participants after
      participation in the CD-ROM program, raising doubts that patients were adequately
      informed to make appropriate choices regarding their treatment. Lower prostate
      cancer knowledge scores corresponded to lower literacy scores, indicating that
      low literacy may have hindered patient understanding of the shared decision
      making program. The development of shared decision making tools should include
      collaborative efforts with the target population to improve the success of shared
      decision making programs among patients with low health literacy.

PMID- 11577810
TI  - Nerve growth factor receptor immunoreactivity in breast cancer patients.
AB  - Nerve growth factor receptor (NGF-R) has been shown to have antiproliferative,
      differentiative, or apoptotic effects on some types of tumor cells, whereas in
      others it may have mitogenic activity. The immunohistochemical distribution of
      NGF-R was analyzed in a series of tissue samples from breast cancer patients and
      its relationship with other clinical and pathological parameters was studied. The
      distribution of NGF-R was evaluated by immunohistochemistry in frozen tissue
      samples of 46 breast cancer patients (ME20-4 monoclonal anti-NGF-R). NGF-R
      immunoreactivity was localized in the plasma membrane of myoepithelial cells,
      differentiated ducts, neoplastic cells, blood vessels, and nerve fibers in 26
      patients (57%). Less differentiated neoplastic tissues were usually NGF-R
      negative. NGF-R immunoreactivity was associated with estrogen receptor (ER)
      status (p = 0.02), small tumor dimension (pT) (p = 0.04), low histologic grade
      (G1-G2) (p < 0.05), old age (p = 0.02), menopause (p = 0.02), and long disease
      free survival (DFS) (median follow up 86 months; p = 0.03; independently from ER,
      pT, age, menopause by multivariate analysis, p = 0.0078). The expression of NGF-R
      immunoreactivity by breast cancer patients with long DFS may represent a crucial
      step both in the differentiation status of neoplasia and in the host immune
      mechanism controlling tumor growth and metastasization.

PMID- 11577811
TI  - Influence of the ward colon tumor on the innate and endotoxin-induced
      inflammatory response of the rat.
AB  - Cachexia, a depressed immune function, and an increased infection rate are
      recurring problems for cancer patients; the response of the host to an infection
      may also be increased. We have reported that the transplantable Ward colon tumor
      (WCT) enhanced the lethality of endotoxin (lipopolysaccharide [LPS]) to the host.
      The mechanism of this increased LPS lethality and the effect of the presence of
      the WCT on the host inflammatory response, however, have not been reported. The
      effect of a transplantable WCT on the innate and endotoxin-induced inflammatory
      response of rats was, therefore, investigated. The innate inflammatory response
      was investigated in two ways. First, the formation of a granuloma around a
      sterile string implanted subcutaneously for 6 days was determined. Second, the
      effect of tumor presence on the trafficking of leukocytes to a sponge implanted
      subcutaneously for 2 or 6 days was determined. The tumor decreased the foreign
      body granuloma formation around a sterile string. The presence of the WCT also
      significantly blunted the increase of lymphocytes that migrated to the sponge
      area at 6 days. There was no significant effect of the WCT, however, on the
      migration of neutrophils, monocytes, or eosinophils to the implanted sponge. The
      leukocyte distribution of the peripheral blood was not affected by the presence
      of the WCT or implantation of a sterile string or sponge. To determine the effect
      of the presence of the WCT on the response of the host to an infection, rats were
      given LPS (5 mg/kg, i.p.) and the alanine amino transferase (ALT) of plasma and
      inducible isoforms of nitric oxide synthase (NOS2) protein content of liver,
      spleen, and terminal ileum was determined. The LPS challenge resulted in an
      increase in plasma ALT concentrations and NOS2 protein content of liver and
      spleen, but not the terminal ileum of WCT rats. This elevation in WCT rats
      confirms that the enhanced LPS-related toxicity in WCT rats was related to an
      increased liver toxicity. The increased toxicity may be related to an increase in
      the nitric oxide synthesis of the liver. These results suggest that the WCT, and
      possibly other tumors, will reduce the ability of the host to respond to a
      foreign body. If this were an infection, the host would be more likely to succumb
      to the resulting inflammatory mediators. Further evaluations of the lymphocyte
      subsets and cytokines in the sponge exudate will be required to completely
      understand this response.

PMID- 11577812
TI  - Adjuvant treatment in node-negative, postmenopausal breast cancer.

PMID- 11577813
TI  - Progress in understanding fatigue associated with breast cancer treatment.
AB  - Fatigue is one of the most common and distressing symptoms reported by cancer
      patients. This article reviews research that has examined the extent to which
      breast cancer patients experience fatigue during and following completion of
      chemotherapy and radiotherapy. The article also addresses methodological issues
      in the study of fatigue as well as the current status of efforts to prevent or
      relieve fatigue associated with breast cancer treatment.

PMID- 11577814
TI  - The role of CXC chemokines in the regulation of tumor angiogenesis.

PMID- 11577815
TI  - The silent epidemic: tobacco and the evolution of lung cancer and its treatment.
AB  - Considered a rare disease during the 19th century, lung cancer became the most
      virulent and lethal cause of cancer mortality by the end of the 20th century. In
      this paper, lung cancer and its treatment are addressed within the social,
      cultural, economic, and political context of the last century. Because lung
      cancer is related to the consumption of cigarettes, the battles over tobacco
      control are highlighted. Four time periods are addressed: the early years (1900
      1930), beginning of the epidemic (1930-1960), defining the problem (1960-1980),
      and expanding options (1980-1990s). Although improvements have been made in
      science and technology, attempts at finding curative treatments have met with
      little success. Smoking cessation and efforts to control tobacco (especially
      among children and adolescents) remain the most important factors if the
      incidence of lung cancer is to be curtailed in the future. Providing care to
      individuals with the illness is a current challenge. Research examining the
      efficacy of treatments and their effect on survival, health-related quality of
      life, and cost outcomes is essential and can be best achieved through the efforts
      of multidisciplinary teams.

PMID- 11577816
TI  - Tobacco and the legacy of lung cancer.

PMID- 11577817
TI  - A new family of mediators of tumor angiogenesis.

PMID- 11577818
TI  - What is the "best" platinum: cisplatin, carboplatin, or oxaliplatin?

PMID- 11577819
TI  - Development of inferential measurements using neural networks.
AB  - In many industrial processes, the most desirable variables to control are
      measured infrequently off-line in a quality control laboratory. In these
      situations, use of advanced control or optimization techniques requires use of
      inferred measurements generated from correlations. For well-understood processes,
      the structure of the correlation as well as the choice of inputs may be known a
      priori. However, many industrial processes are too complex and the appropriate
      form of the correlation and choice of input measurements are not obvious. Here,
      process knowledge, operating experience, and statistical methods play an
      important role in development of correlations. This paper describes a systematic
      approach to the development of nonlinear correlations for inferential
      measurements using neural networks. A three-step procedure is proposed. The first
      step consists of data collection and preprocessing. Next, the process variables
      are subjected to simple statistical analyses to identify a subset of measurements
      to be used in the inferential scheme. The third step involves generation of the
      inferential scheme. We demonstrate the methodology by inferring the ASTM 95%
      endpoint of a petroleum product using data from a domestic US refinery.

PMID- 11577820
TI  - Quantitative feedback synthesis of sampled-data systems with time-delay by
      approximate Z-transform.
AB  - In this paper, the equivalent disturbance rejection (EDR) in QFT design
      methodology is proposed for dealing with sampled-data systems with time-delay.
      This EDR is mainly to overcome the non-minimum phase zero generated by the first
      order Pade' approximation of the time-delay factor. Due to plant parameter
      uncertainty, the analogue controller is to be designed so that the system
      response lies within permissible bounds. By approximate Z-transform, the analogue
      controller can be transformed directly into a digital one and then the analogue
      plant is transformed into the digital plant, with sampling time as a free
      parameter. By adjusting the sampling time, the uncertain sampled-data system can
      be stabilized. In comparison with other approaches, our design framework is much
      more systematic by using only algebraic manipulations and transparent enough to
      guide the designer to realize the physical controller for the plant with
      prescribed bounds on its parameters.

PMID- 11577821
TI  - Placing all closed loop poles of missile attitude control systems in the sliding
      mode via the root locus technique.
AB  - This paper presents a robust control method for uncertain nonminimum phase
      systems with external disturbances. A systematic design algorithm is developed
      which links the sliding mode control and the root locus technique. Complete
      closed-loop pole placement is achieved in addition to the placement of the
      reduced order equivalent system poles. An integration function is employed in the
      sliding variable formulation. The output tracking error is guaranteed to vanish.
      The proposed method was successfully applied to control the angle of attack of a
      missile attitude control system.

PMID- 11577822
TI  - Guide lines for the tuning and the evaluation of decentralized and decoupling
      controllers for processes with recirculation.
AB  - This paper gives guidelines for the pairing, the time response specification, and
      the tuning for processes with recirculation when decentralized controllers are
      used. This selection is based on the condition number, which is an indicator of
      the process directionality, and on the generalized dynamic relative gain (GDRG),
      which is a measure of the interaction. Simple tuning rules are developed and
      results are compared to algebraic controllers with decouplers. Performances are
      evaluated for set-point changes as well as disturbance rejection using the
      generalized step response (GSR). The GSR gives a 3D graphic of the system
      response as a function of the input direction.

PMID- 11577823
TI  - A comparison of traditional and adaptive control strategies for systems with time
      delay.
AB  - A recently developed tuning method is compared to an adaptive Smith Predictor
      control strategy. The robustness of each method is considered for time-varying
      plant parameters. Examples with simulations are provided to compare the methods
      and present conclusions on the advantages and disadvantages of each.

PMID- 11577824
TI  - Nonlinear mill control.
AB  - A mill is a mechanical device that grinds mined or processed material into small
      particles. The process is known to display significant deadtime, and, more
      notably, severe nonlinear behavior. Over the past 25 years attempts at continuous
      mill control have met varying degrees of failure, mainly due to model mismatch
      caused by changes in the mill process gains. This paper describes an on-line
      control application on a closed-circuit cement mill that uses nonlinear model
      predictive control technology. The nonlinear gains for the control model are
      calculated on-line from a neural network model of the process.

PMID- 11577825
TI  - Optimisation of fed-batch culture of hybridoma cells using genetic algorithms.
AB  - In this paper, a program describing a genetic algorithm is used for optimising
      fed-batch culture hybridoma cells to obtain the highest yield over certain time
      period. Optimal feed rate trajectories for a single feed stream containing both
      glucose and glutamine, and separate feed streams of glucose and glutamine are
      determined via the genetic algorithm. As compared to the optimal constant feed
      rate regime, optimal varying feed rate trajectories improve the final monoclonal
      antibodies concentration by 10% for the single feed rate case and by 39% for the
      multi feed rate case in this simulation. In comparsion with a dynamic
      programming, GA calculated feed trajectories yield a much higher level of
      monoclonal antibodies concentration.

PMID- 11577826
TI  - Tolerable risk guidelines.
AB  - Safety instrumented systems (SIS) should be designed to reduce the amount of risk
      in a process to a tolerable level. Expressing the tolerable level of risk is one
      of the most difficult tasks facing organizations trying to comply with the
      standards that govern SIS use. Organizations are basing their risk decision
      making criteria on a variety of benchmarks including industry standards, local
      and foreign government regulations, practices of industry partners, and a
      qualitative assessment of what is fair and reasonable. This paper explores the
      ways that industry and government have made decisions on what risks are
      tolerable. The paper begins by reviewing qualitative criteria that are evaluated
      to determine what amount of risk can reasonably be tolerated. The paper also
      reviews some methods that have been used in government and industry to include
      financial aspects into the decision-making process. It then proceeds to review
      some of the quantitative ways that risk is represented. After discussing risk
      presentation, the paper reviews and compares tolerable risk guidelines that have
      been set by government and industry. The paper concludes by comparing the amount
      of risk reduction that can be justified by sociopolitical tolerability guidelines
      and that which can be justified by cost-benefit analysis.

PMID- 11577827
TI  - Microarray-based genetics of cardiac malformations.
AB  - One of the most revolutionary approaches in human genomics is DNA microarray
      technology. Latest developments have brought this technology to a widespread use.
      In this paper we discuss its usefulness especially for the study of the genetic
      component in congenital heart disease as a model of multifactorial disease and
      the possible clinical applications in the near future. Malformations of the heart
      and blood vessels account for the largest number of human birth defects. The
      susceptibility of the heart to developmental anomalies reflects the complexity of
      the morphogenetic events responsible for the heart formation. The genetics of
      congenital heart disease points to the existence of powerful disease modifiers.
      Tissue analysis of gene expression with cDNA microarrays provides a measure of
      transcriptional or posttranscriptional regulation. Large-scale partial sequencing
      of cDNA libraries generating expressed sequence tags is an effective means of
      discovering novel genes and characterizing transcription patterns in different
      organs and tissues. The qualitative and quantitative analysis of genes expressed
      in cardiac tissue by means of comparison of expression patterns related to the
      normal and to the pathological tissue may be of great importance for the study of
      cardiac pathologies. The variation in phenotypic penetrance and severity suggests
      that if we can identify high-risk individuals, a reduction in infant morbidity
      might be possible by altering environmental or maternal factors.

PMID- 11577828
TI  - Microarray-based genetic analyses for studying susceptibility to arterial and
      venous thrombotic disorders.
AB  - We describe the potential of microarray technology for parallel, high-throughput
      approaches to molecular detection of DNA variations associated with progression
      to arterial and venous thrombotic diseases. The use of the newly commercialized
      NanoChip platform and a framework for genetic screening with a list of potential
      genetic targets useful to the evaluation of cardiovascular risk are presented.
      Implementation in clinical setting of analytical silicon and glass microarrays
      will facilitate early diagnosis, help direct specific advice to high-risk
      individuals and evaluate treatment strategies.

PMID- 11577829
TI  - Atrioventricular junction ablation and pacemaker in patients with heart failure
      and permanent atrial fibrillation.

PMID- 11577830
TI  - Is the heart period a linear gauge of autonomic neural activity?

PMID- 11577831
TI  - Aspirin and the prevention of ischemic heart disease. A Socratic dialogue between
      a cardiologist, a clinical pharmacologist and an expert of blood platelets.
AB  - The recent publication of the results of the "Progetto di Prevenzione Primaria"
      by a large Italian group of researchers and general practitioners, prompts a
      cardiologist, a clinical pharmacologist and a blood platelet expert to review -
      using a Socratic dialogue style--the data on aspirin as a prototypal drug in the
      prevention of ischemic heart disease. The distinction between primary and
      secondary prevention seems to be rather artificial as it is based on past events
      and not on the risk of future events. Although aspirin proved to be effective in
      reducing both vascular mortality and non-fatal vascular events and is
      inexpensive, it is still underused for prevention by many physicians. The major
      indications on the beneficial effect of aspirin against ischemic heart disease
      derive from large epidemiological trials and are valid for populations rather
      than for single patients. Hopefully, biochemical markers such as C-reactive
      protein or genetic polymorphism will help to establish the effects of aspirin in
      more targeted groups or even in individuals.

PMID- 11577832
TI  - Angiotensin-related genes involved in essential hypertension: allelic
      distribution in an Italian population sample.
AB  - BACKGROUND: Blood pressure is a quantitative multifactorial trait influenced by
      environmental and genetic determinants. Although several candidate genes have
      been associated with the development of essential hypertension, the mechanisms of
      individual susceptibility still remain unclear. Knowledge on the distribution of
      genetic polymorphisms in different populations is fundamental for the assessment
      of the predictive value of genetic variation. METHODS: We genotyped 300 healthy
      normotensive subjects from the Italian population for three polymorphisms, at the
      angiotensinogen (AGT, M and T), angiotensin II type 1 receptor (ATIR, A and C)
      and angiotensin-converting enzyme (ACE, D and I) genes. Polymorphisms were
      analyzed by polymerase chain reaction and restriction enzyme digestion.
      Statistical analysis was performed to verify the agreement with the Hardy
      Weinberg equilibrium. RESULTS: The observed allelic distribution was in
      accordance with estimates reported for Caucasian populations. Variant allelic
      frequencies were 0.36 for the T and C alleles at the AGT andAT1R locus and 0.47
      for the I allele of the ACE gene. AT1R and ACE genotype frequencies were in Hardy
      Weinberg equilibrium, while there was a deviation of the AGT genotypes from those
      predicted by the equation. CONCLUSIONS: The studied polymorphisms are largely
      distributed in the Italian population sample, with a frequency of homozygous
      subjects for mutant alleles ranging from 9 to 22%. Epidemiology of mutations in
      the genes involved in blood pressure regulation provides tools to evaluate
      susceptibility to hypertension.

PMID- 11577833
TI  - Whole-body bioelectrical impedance analysis in patients with chronic heart
      failure: reproducibility of the method and effects of body side.
AB  - BACKGROUND: Fluid imbalance and malnutrition have an important role in the
      clinical setting of chronic heart failure (CHF). Recently, tetrapolar
      bioelectrical impedance analysis has been suggested as an attractive method which
      may be used in the clinical assessment of the body composition. The aim of this
      study was to determine the effects of body side on whole bioelectrical impedance
      analysis parameters and test-retest reliability, prior to its use in a large
      cohort of patients. METHODS: In 114 consecutive patients with CHF (mean age 65 +/
      10 years, left ventricular ejection fraction 31 +/- 9%, NYHA functional class
      2.6 +/- 0.9) we measured the total body resistance, the reactance and the derived
      angle phase using a single-frequency (50 KHz) tetrapolar plethysmograph device.
      The evaluations were performed on the left and right sides of the body, in a
      random order, on two different occasions 30 min apart. The effects of body side
      were analyzed by the Student's t-test and the test-retest reliability was
      computed by using the coefficient of variation and intraclass correlation
      coefficient. RESULTS: In both evaluations, the mean resistance value of the right
      side was significantly lower (almost 10 ohms) than that of the left side, the
      reactance was not different, and as a consequence the angle phase was
      significantly higher (almost 0.1 degrees) in the right than in the left side. The
      test-retest reliability for all the measurements considered was very high (the
      intraclass correlation coefficient ranged from 0.95 to 0.99 and the coefficient
      of variation from 1.7 to 4.3%). CONCLUSIONS: In CHF, the body side is important
      for the whole-body assessment of the resistance and the angle phase, but not for
      reactance. In addition, all these measurements are characterized by an excellent
      test-retest reliability and, consequently, do not necessitate a substantial
      increase in the sample size for the detection of small differences in
      experimental studies.

PMID- 11577834
TI  - Relation of heart rate to left ventricular dimensions in normotensive, normal
      weight children, adolescents and adults.
AB  - BACKGROUND: The quantitative relation between body growth and changes in heart
      rate, and the relationship of heart rate to left ventricular (LV) dimensions,
      independent of the influence of body size, have been only marginally
      investigated. Accordingly, we designed this study to investigate the relation
      between heart rate, body size and LV dimensions in children, adolescents and
      adults over a broad age span. METHODS: Eight hundred and nineteen normotensive,
      multi-racial, normal-weight individuals (444 males, 375 females, aged 1-85 years)
      with normal LV systolic function were studied at echocardiography in three
      centers, using previously reported methods. The resting heart rate was measured
      on the M-mode echo-tracing or right after the echocardiogram with the subject
      still in the supine position. RESULTS: In children and adolescents (up to 17
      years), the heart rate decreased with increasing body height (r = -0.51, p <
      0.0001) and body weight (r = -0.42, p < 0.0001), in a similar manner in girls and
      boys. In adults, the heart rate was higher in women than in men, but it was not
      independently related to body size. The LV diastolic diameter was higher in males
      and decreased with increasing heart rate in children and adolescents (r = -0.45)
      as well as in adults (r = -0.25, both p < 0.0001). This relation was also
      independent of the effect of body size, sex and race. Similarly, the LV mass
      increased with decreasing heart rate in children and adolescents (r = -0.45), but
      the association was not confirmed after controlling for body size, sex and race.
      In adults, heart rate was inversely related to LV mass (r = -0.21, p < 0.0001),
      and this relation was also independent of body size, sex, race, age and blood
      pressure (p < 0.001). In women, the relation of heart rate to LV mass/height2.7
      was less close than in men, due to the greater increase in LV mass with age.
      CONCLUSIONS: The heart rate has an inverse association with the LV chamber
      diameter and with the LV mass in children-adolescents and in adults. This
      relation is largely, but not uniquely, mediated by body proportions, especially
      during body growth.

PMID- 11577835
TI  - Safety and efficacy of thrombolysis with alteplase (50 mg) plus tirofiban versus
      alteplase (100 mg) alone in acute myocardial infarction: preliminary findings.
AB  - BACKGROUND: The goal of therapy in acute myocardial infarction (AMI) is the
      complete and timely restoration of coronary blood flow. Platelets have a pivotal
      role in the pathophysiology of AMI. The study was aimed at evaluating the safety
      and efficacy of the combination of 50 mg alteplase plus tirofiban vs 100 mg
      alteplase in AMI patients. METHODS: One hundred twenty patients (83 males, 37
      females; mean age 54.3 +/- 8 years) were hospitalized for suspected AMI within 6
      hours of the onset of symptoms. All patients presented pain and persistent ST
      segment elevation, were suitable candidates for thrombolysis (1st episode) and
      were randomized (double blind) into two groups. Group A (n = 60,42 males, 18
      females) received 50 mg alteplase (15 mg as bolus, followed by an infusion of 35
      mg over 60 min) in combination with tirofiban (0.4 mcg/kg/min for 30 min followed
      by an infusion of 0.1 mcg/kg/min for 3 days). Group B (n = 60, 41 males, 19
      females) received 100 mg of accelerated-dose alteplase alone. Reperfusion
      criteria were defined as follows: > 50% reduction in the ST-segment elevation;
      resolution of chest pain; double marker of creatine kinase (CK) and CK-MB
      activity 2 hours after the start of thrombolysis; reperfusion arrhythmias within
      the first 120 min of thrombolysis. The blood pressure, heart rate and ECG were
      continuously monitored. The mortality, re-AMI, recurrent angina, major and minor
      bleeding, and emergency bypass surgery or coronary angioplasty were checked.
      RESULTS: The groups were similar with regard to clinical data, risk factors, time
      elapsed from the onset of symptoms to thrombolytic therapy and AMI localization.
      Forty-seven patients (78.3%) from group A showed reperfusion (15-60 min) vs 25
      patients (41.7%) from group B (43-105 min after the end of full-thrombolysis, p =
      0.01). Group A patients showed an earlier CK peak and lower CK and CK-MB peaks
      than those in the control group (p = 0.0001, p = 0.011, p = 0.005, respectively).
      Nine patients (7.5%) died: 6 (10%) in group B and 3 (5%) in group A (p = NS). A
      non-fatal re-AMI occurred in 8 patients from group A and in 4 patients from group
      B (p = NS). Recurrent angina occurred in 27 patients (45%) from group A and in 11
      (18.3%) from group B (p = 0.037). Twenty-three of these patients underwent urgent
      coronary angioplasty (17 from group A and 6 from group B) and 3 from group A and
      1 from group B underwent urgent coronary artery bypass grafting (p = NS). The
      frequency of minor bleeding was higher in group A than in group B (56.7 vs 25%, p
      = 0.033). No major bleeding was observed in the study groups. At the predischarge
      echocardiogram, the ejection fraction was higher in group A than in group B (50
      +/- 9 vs 44 +/- 7%, p = 0.001). CONCLUSIONS: Our data suggest that the
      combination of glycoprotein IIb/IIIa inhibitors plus alteplase is feasible in AMI
      patients and that the increased risk of bleeding is an acceptable risk
      considering the advantage in terms of the reduction in the extent of an AMI. In
      addition, this combination can allow one to gain time when it is necessary to
      perform mechanical revascularization in patients admitted to a hospital without
      an interventional cardiology laboratory or in those who have to be referred to
      another hospital for urgent coronary artery bypass grafting.

PMID- 11577836
TI  - Noninvasive prediction of sudden death and sustained ventricular tachycardia
      after acute myocardial infarction using a neural network algorithm.
AB  - BACKGROUND: The early and accurate noninvasive identification of postinfarction
      patients at risk of sudden death and sustained ventricular tachycardia
      (arrhythmic events) still remains an unsolved problem. The aim of the present
      study was to identify the combination of clinical and laboratory noninvasive
      variables, easy to obtain in most patients, that best predicts the occurrence of
      arrhythmic events after an acute myocardial infarction. METHODS: Four hundred and
      four consecutive patients with acute myocardial infarction were enrolled and
      followed for a median period of 21.4 months. In each patient, 61 clinical and
      laboratory noninvasive variables were collected before hospital discharge and
      used for the prediction of arrhythmic events using an artificial neural network.
      RESULTS: During follow-up, 13 (3.2%) patients died suddenly and 11(2.5%) had
      sustained ventricular tachycardia. The neural network showed that the combination
      best predicting arrhythmic events included: left ventricular failure during
      coronary care stay, ventricular dyskinesis, late potentials, number of
      ventricular premature depolarizations/hour, nonsustained ventricular tachycardia,
      left ventricular ejection fraction, bundle branch block and digoxin therapy at
      discharge. The neural network algorithm allowed identification of a small high
      risk patient subgroup (12% of the study population) with an arrhythmic event rate
      of 46%. The sensitivity and specificity of the test were 96 and 93% respectively.
      CONCLUSIONS: These results suggest that, in postinfarction patients, it is
      possible to predict early and accurately arrhythmic events by noninvasive
      variables easily obtainable in most patients. Patients identified as being at
      risk are candidates for prophylactic antiarrhythmic therapy.

PMID- 11577837
TI  - Lipoma of the heart: a case report.
AB  - Lipomas of the heart are rare (only 0.5% according to the Armed Forces Institute
      of Pathology series) and their diagnosis is often difficult because they are
      asymptomatic; in fact, in contrast to lipomatous hypertrophy, lipomas are usually
      found on the epicardial surfaces of the atria or ventricles. In our case, the
      lipoma was located in both atria and was attached to the interatrial septum
      involving also the right pulmonary veins, the inferior vena cava and the right
      phrenic nerve. At histology, the tumor was composed only of mature adipose tissue
      with entrapped myocytes and vessels. The combination of computed tomography and
      transesophageal echocardiography allowed a precise diagnosis in terms of the
      localization and tissue characterization of the tumor.

PMID- 11577838
TI  - Aortico-left ventricular tunnel: two new cases with a long-term follow-up.
AB  - Aortico-left ventricular tunnel is a rare congenital communication between the
      ascending aorta and the left ventricle. Its hemodynamic effect is severe aortic
      incompetence. Surgery is the only treatment and should be performed before aortic
      incompetence or ventricular dilation develops. Two neonates with aortico-left
      ventricular tunnel were operated on at our institution, with closure of the
      aortic end of the tunnel with a Gore-Tex patch. The 2 patients were discharged in
      good conditions, and at 112 and 42-month follow-up respectively they are in good
      health, without medication and with a normal echocardiographic pattern. Aortico
      left ventricular tunnel should be treated surgically as soon as possible in order
      to prevent any damage to the aortic valve and the left ventricle. The operative
      risk is not low, but results are very encouraging.

PMID- 11577839
TI  - Giant anastomotic pseudoaneurysm after Bentall operation causing late
      postoperative cardiogenic shock.
AB  - Pseudoaneurysm of the ascending aorta is a rare but severe complication occurring
      after composite graft surgery for combined aortic valve and ascending aorta
      disease. The diagnosis of this condition can be difficult because anastomotic
      pseudoaneurysms show highly variable clinical features depending on the site of
      the aortic dehiscence and on the involvement of the surrounding structures. We
      report an unusual case of a late postoperative aortic graft dehiscence, causing
      acute right heart failure.

PMID- 11577840
TI  - Partial left-sided pericardial absence mimicking a cardiac tumor.

PMID- 11577841
TI  - Diagnosis of the superior sinus venosus defect by intracardiac echocardiography.

PMID- 11577842
TI  - The surgical volume reduction for dilated cardiomyopathy.

PMID- 11577843
TI  - Multifocal coronary thrombi during acute myocardial infarction.

PMID- 11577844
TI  - Ethnicity, coping, and distress among Korean Americans, Filipino Americans, and
      Caucasian Americans.
AB  - The authors examined appraisal, coping, and distress among Korean American,
      Filipino American, and Caucasian American Protestants. No interaction effects
      emerged among ethnic groups, but there were significant ethnic main effects for
      appraisal and coping. Compared with the Caucasian Americans, both Asian American
      groups appraised stressors as more challenging, and the Korean Americans
      appraised them also as greater losses. Both Asian American groups reported using
      more strategies of accepting responsibility, religious coping, distancing, and
      escape-avoidance than the Caucasian Americans did; the Filipino Americans also
      reported more problem-solving strategies than the Caucasian Americans. For all
      participants, challenge appraisals predicted adaptive coping (problem solving and
      positive reappraisal) and less distress. Problem solving, seeking social support,
      and positive reappraisal predicted less distress; self-control, accepting
      responsibility, and escape-avoidance predicted greater distress. The authors
      stressed the value of assessing ethnicity in coping research.

PMID- 11577845
TI  - Psychological correlates of perception of sexual intent in women.
AB  - In a sample of 183 men and 186 women, the authors assessed (a) the relative
      contributions of gender and level of nonverbal social cues to the perception of a
      female actor's sexual intent during a videotaped social interaction with a man
      and (b) the association between those variables and personality traits implicated
      in faulty sexual-information processing. The authors assessed those variables
      while the participants viewed 1 of 3 film segments depicting a female-male
      interaction. The authors experimentally manipulated eye contact, touch, physical
      proximity, and female clothing. At all levels of those nonverbal cues, the men
      perceived more sexual intent in the female actor than did the women. The
      perception of the female actor's sexual intent increased as the nonverbal cues in
      the film segments were magnified: Both actors displayed more eye contact, touch,
      and physical proximity, and the female actor wore more revealing clothing.
      Relative to the women, the men demonstrated greater sexual preoccupation and
      reduced sociosexual effectiveness, variables associated with inferring greater
      sexual intent in the female actor.

PMID- 11577846
TI  - Attitudes of future human service professionals: the effects of victim and helper
      qualities.
AB  - The authors determined the effects of the qualities of trauma victims (ethnic
      background, level of trauma, level of adaptation) and of helpers (gender, type of
      education, field of study) on the attitudes of future members of human service
      professions (law, medicine, nursing, social sciences, law enforcement) toward the
      victims. The respondents read 6 descriptions of a fictitious victim and rated
      their general attitudes toward the victim described. The high-trauma and poorly
      adapted victims elicited more negative attitudes than did the low-trauma and well
      adapted victims. The male respondents and those from vocational institutions had
      more negative attitudes toward the victims. The female respondents and those from
      the university expressed more positive attitudes. The future police officers and
      legal professionals tended to have more negative attitudes toward the victims
      than did the future medical and social care professionals. The findings did not
      support the assumption that the participants would hold more negative attitudes
      toward other-ethnic than toward same-ethnic victims.

PMID- 11577847
TI  - Cultural values and happiness: an East-West dialogue.
AB  - Happiness as a state of mind may be universal, but its meaning is complex and
      ambiguous. The authors directly examined the relationships between cultural
      values and experiences of happiness in 2 samples, by using a measurement of
      values derived from Chinese culture and a measurement of subjective well-being
      balanced for sources of happiness salient in both the East and the West. The
      participants were university students-439 from an Eastern culture (Taiwan) and
      344 from a Western culture (the United Kingdom). Although general patterns were
      similar in the 2 samples, the relationships between values and happiness were
      stronger in the Taiwanese sample than in the British sample. The values social
      integration and human-heartedness had culture-dependent effects on happiness,
      whereas the value Confucian work dynamism had a culture-general effect on
      happiness.

PMID- 11577848
TI  - The effects of apology and perspective taking on interpersonal forgiveness: a
      dissonance-attribution model of interpersonal forgiveness.
AB  - The author investigated (a) the effects of a victim's perspective taking and a
      transgressor's apology on interpersonal forgiveness and (b) forgiveness as a mode
      of dissonance reduction. Before the participants read a scenario describing a
      situation in which they imagined being mistreated by a classmate, the author
      randomly assigned them to 1 of 4 perspective-taking conditions: (a) recalling
      times when they had mistreated or hurt others (i.e., the recall-self-as
      transgressor condition); (b) imagining how they would think, feel, and behave if
      they were the classmate (i.e., the imagine-self condition); (c) imagining how the
      classmate would think, feel, and behave (i.e., the imagine-other condition); or
      (d) imagining the situation from their own (i.e., the victim's/control)
      perspective. After reading the scenario, the participants read an apology from
      the classmate. The participants in the recall-self-as-transgressor condition were
      significantly more likely than those in the control condition to (a) make
      benevolent attributions, (b) experience benevolent emotional reactions, and (c)
      forgive the transgressor. The relationship between the perspective-taking
      manipulation and forgiveness was mediated by the benevolent attributions and
      positive emotional reactions experienced by the victims.

PMID- 11577849
TI  - The accessibility of group memberships.
AB  - The authors performed 2 experiments to examine the accessibility of thoughts
      about group memberships (i.e., collective self-cognitions) relative to thoughts
      about traits, states, and behaviors (i.e., private self-cognitions). Few
      collective self-cognitions were accessible for the present participants from an
      individualist culture. Furthermore, collective self-cognitions were highly
      associated with each other in a self-structure. The findings were interpreted in
      terms of the two-baskets theory that private and collective self-cognitions tend
      to be stored relatively separately in memory (D. Trafimow, H.C. Triandis, & S.G.
      Goto, 1991).

PMID- 11577850
TI  - Emotional intelligence and interpersonal relations.
AB  - In 7 studies, the authors examined the link between emotional intelligence and
      interpersonal relations. In Studies 1 and 2, the participants with higher scores
      for emotional intelligence had higher scores for empathic perspective taking and
      self-monitoring in social situations. In Study 3, the participants with higher
      scores for emotional intelligence had higher scores for social skills. In Study
      4, the participants with higher scores for emotional intelligence displayed more
      cooperative responses toward partners. In Study 5, the participants with higher
      scores for emotional intelligence had higher scores for close and affectionate
      relationships. In Study 6, the participants' scores for marital satisfaction were
      higher when they rated their marital partners higher for emotional intelligence.
      In Study 7, the participants anticipated greater satisfaction in relationships
      with partners described as having emotional intelligence.

PMID- 11577851
TI  - Effects of nonverbal behavior on perceptions of a female employee's power bases.
AB  - The authors extended a previous examination of the effects of nonverbal behavior
      on perceptions of a male employee's power bases (H. Aguinis, M. M. Simonsen, & C.
      A. Pierce, 1998) by examining the effects of nonverbal behavior on perceptions of
      a female employee's power bases. U.S. undergraduates read vignettes describing a
      female employee engaging in 3 types of nonverbal behavior (i.e., eye contact,
      facial expression, body posture) and rated their perceptions of the woman's power
      bases (i.e., reward, coercive, legitimate, referent, expert, credibility). As
      predicted, (a) direct eye contact increased perceptions of coercive power, and
      (b) a relaxed facial expression decreased perceptions of all 6 power bases. Also
      as predicted, the present results differed markedly from those of Aguinis et al.
      (1998) regarding a male employee. The authors discuss implications for theory,
      future research, and the advancement of female employees.

PMID- 11577852
TI  - Gender comparisons in the private, collective, and allocentric selves.
AB  - Researchers (e.g., M. B. Brewer & W. Gardner, 1996; H. C. Triandis, D. K. S.
      Chan, D. P. S. Bhawuk, S. Iwao, & J. P. B. Sinha, 1995) have suggested expansion
      of the standard model of individualism-collectivism to include people's close
      personal relationships in addition to their identification with in-groups. There
      has been considerable discussion of the hypothesis that women are more
      collective, interdependent, relational, and allocentric than men (e.g., S. E.
      Cross & L. Madson, 1997; Y. Kashima et al., 1995). In the present study, the
      authors used the Twenty Statements Test (M. H. Kuhn & T. McPartland, 1954) to
      examine gender differences in the self-concept by assessing the accessibility of
      private, collective, and allocentric self-cognitions. The U.S. women described
      themselves with more allocentric and more collective self-cognitions than did the
      U.S. men. Discussion focuses on the implications of those data for interpretation
      of other gender differences as well as for traditional models of individualism
      collectivism.

PMID- 11577853
TI  - A modified risk assessment to establish molybdenum standards for land application
      of biosolids.
AB  - The USEPA standards (40 CFR Part 503) for the use or disposal of sewage sludge
      (biosolids) derived risk-based numerical values for Mo for the biosolids --> land
      --> plant --> animal pathway (Pathway 6). Following legal challenge, most Mo
      numerical standards were withdrawn, pending additional field-generated data using
      modern biosolids (Mo concentrations <75 mg kg(-1) and a reassessment of this
      pathway. This paper presents a reevaluation of biosolids Mo data, refinement of
      the risk assessment algorithms, and a reassessment of Mo-induced hypocuprosis
      from land application of biosolids. Forage Mo uptake coefficients (UC) are
      derived from field studies, many of which used modern biosolids applied to
      numerous soil types, with varying soil pH values, and supporting various crops.
      Typical cattle diet scenarios are used to calculate a diet-weighted UC value that
      realistically represents forage Mo exposure to cattle. Recent biosolids use data
      are employed to estimate the fraction of animal forage (FC) likely to be affected
      by biosolids applications nationally. Field data are used to estimate long-term
      Mo leaching and a leaching correction factor (LC) is used to adjust cumulative
      biosolids application limits. The modified UC and new FC and LC factors are used
      in a new algorithm to calculate biosolids Mo Pathway 6 risk. The resulting
      numerical standards for Mo are cumulative limit (RPc)=40 kg Mo ha(-1), and
      alternate pollutant limit (APL) = 40 mg Mo kg(-1) We regard the modifications to
      algorithms and parameters and calculations as conservative, and believe that the
      risk of Mo-induced hypocuprosis from biosolids Mo is small. Providing adequate Cu
      mineral supplements, standard procedure in proper herd management, would augment
      the conservatism of the new risk assessment.

PMID- 11577854
TI  - Spatiotemporal variability of wet atmospheric nitrogen deposition to the Neuse
      River Estuary, North Carolina.
AB  - Excessive nitrogen (N) loading to N-sensitive waters such as the Neuse River
      estuary (North Carolina) has been shown to promote changes in microbial and algal
      community composition and function (harmful algal blooms), hypoxia and anoxia,
      and fish kills. Previous studies have estimated that wet atmospheric deposition
      of nitrogen (WAD-N), as deposition of dissolved inorganic nitrogen (DIN: NO3-,
      NH3/NH4+) and dissolved organic nitrogen, may contribute at least 15% of the
      total externally supplied or "new" N flux to the coastal waters of North
      Carolina. In a 3-yr study from June 1996 to June 1999, we calculated the weekly
      wet deposition of inorganic and organic N at eleven sites on a northwest
      southeast transect in the watershed. The annual mean total (wet DIN + wet
      organics) WAD-N flux for the Neuse River watershed was calculated to be 956 mg
      N/m2/yr (15026 Mg N/yr). Seasonally, the spring (March-May) and summer (June
      August) months contain the highest total weekly N deposition; this pattern
      appears to be driven by N concentration in precipitation. There is also spatial
      variability in WAD-N deposition; in general, the upper portion of the watershed
      receives the lowest annual deposition and the middle portion of the watershed
      receives the highest deposition. Based on a range of watershed N retention and in
      stream riverine processing values, we estimate that this flux contributes
      approximately 24% of the total "new" N flux to the estuary.

PMID- 11577855
TI  - Phytoremediation of aged petroleum sludge: effect of irrigation techniques and
      scheduling.
AB  - The use of higher plants to accelerate the remediation of petroleum contaminants
      in soil is limited by, among other factors, rooting depth and the delivery of
      nutrients to the microsites at which remediation occurs. The objective of this
      study was to test methods of enhancing root growth and remediation in the
      subsurface of a contaminated petroleum sludge. The phytoremediation of highly
      contaminated petroleum sludge (total petroleum hydrocarbons >35 g kg(-1) was
      tested in the greenhouse as a function of the frequency and the depth of
      irrigation and fertilization. Water and dissolved plant nutrients were added to
      the soil surface or at a depth of 30 cm, either daily or weekly. Equivalent
      quantities of water and nutrients were added in all cases. Daily irrigation at a
      depth of 30 cm invoked greater root growth and enhanced contaminant degradation
      relative to all other treatments. In the absence of plants, residual
      concentrations of petroleum hydrocarbons after 7 mo were higher than with plants.
      The presence of plant roots clearly improved the physical structure of the soil
      and increased microbial populations. Thus, the plant roots in conjunction with
      daily additions of soluble N and P appeared to enhance oxygen transport to
      greater depths in the soil, stimulate petroleum-degrading microorganisms, and
      provide microbial access to soil micropores. Subsurface irrigation with frequent,
      small amounts of water and nutrients could significantly accelerate
      phytoremediation of field soils contaminated with petroleum hydrocarbons.

PMID- 11577856
TI  - Kinetic modeling of bioavailability for sorbed-phase 2,4-dichlorophenoxyacetic
      acid.
AB  - The degradation rate of 2,4-dichlorophenoxyacetic acid (2,4-D) was studied in
      silica-slurry systems to evaluate the bioavailability of sorbed-phase
      contaminant. After the silica particles were saturated with 2,4-D, the system was
      inoculated with the 2,4-D-degrading microorganism Flavorbacterium sp. strain FB4.
      The disappearance rate of 2,4-D was found to be greater than the rate predicted
      based upon liquid-phase 2,4-D concentrations. A kinetic formulation, termed the
      enhanced bioavailability model, was developed to describe the desorption and
      biodegradation processes in this batch system. The approach assumes that 2,4-D
      resides in both the liquid and solid phases and degradation occurs via both
      suspended and attached biomass. All biomass can degrade liquid-phase 2,4-D at one
      rate, while only attached biomass can degrade sorbed 2,4-D at another rate. An
      enhanced transformation factor (Ef) was introduced to express the increased
      biodegradation rate over that expected from the liquid phase only. This approach
      was able to account for the increased degradation rates observed experimentally.
      The results provide evidence that desorption to the bulk solution is not
      prerequisite to degradation, and that sorbed substrate may be available for
      degradation.

PMID- 11577857
TI  - Biosolids applications affect runoff water quality following forest fire.
AB  - Soil erosion and nutrient losses are great concerns following forest wildfires.
      Biosolids application might enhance revegetation efforts while reducing soil
      erodibility. Consequently, we applied Denver Metro Wastewater District composted
      biosolids at rates of 0, 40, and 80 Mg ha(-1) to a severely burned, previously
      forested site near Buffalo Creek, CO to increase plant cover and growth. Soils
      were classified as Ustorthents, Ustochrepts, and Haploborols. Simulated rainfall
      was applied for 30 min at a rate of 100 mm h(-1) to 3- x 10-m paired plots.
      Biosolids application rates did not significantly affect mean total runoff (p <
      0.05). Sediment concentrations were significantly greater (p < 0.05) from the
      control plots compared with the plots that had received the 80 Mg biosolids ha(
      1) rate. Biosolids application rate had mixed effects on water-quality
      constituents; however, concentrations of all runoff constituents for all
      treatment rates were below levels recommended for drinking water standards,
      except Pb. Biosolids application to this site increased plant cover, which should
      provide erosion control.

PMID- 11577858
TI  - Movement of coliform bacteria and nutrients in ground water flowing through
      basalt and sand aquifers.
AB  - Large-scale deposition of animal manure can result in contamination of surface
      and ground water and in potential transfer of disease-causing enteric bacteria to
      animals or humans. We measured total coliform bacteria (TC), fecal coliform
      bacteria (FC), NO3, NH4, total P, and PO4 in ground water flowing from basalt and
      sand aquifers, in wells into basalt and sand aquifers, in irrigation water, and
      in river water. Samples were collected monthly for 1 yr. Total coliform and FC
      numbers were always higher in irrigation water than in ground water, indicating
      that soil and sediment filtered most of these bacteria before they entered the
      aquifers. Total coliform and FC numbers in ground water were generally higher in
      the faster flowing basalt aquifer than in the sand aquifer, indicating that the
      slower flow and finer grain size may filter more TC and FC bacteria from water.
      At least one coliform bacterium/100 mL of water was found in ground water from
      both basalt and sand aquifers, indicating that ground water pumped from these
      aquifers is not necessarily safe for human consumption according to the American
      Public Health Association and the USEPA. The NO3 concentrations were usually
      higher in water flowing from the sand aquifer than in water flowing from the
      basalt aquifer or in perched water tables in the basalt aquifer. The PO4
      concentrations were usually higher in water flowing from the basalt aquifer than
      in water flowing from the sand aquifer. The main concern is fecal contamination
      of these aquifers and health consequences that may arise from human consumption.

PMID- 11577859
TI  - A transport model with coupled ternary exchange and chemisorption retention for
      hydrazinium cations.
AB  - A numerical model was developed to describe the fate and transport of hydrazinium
      (N2H5+) and competing Ca2+ and H+ cations applied in acidic solutions to columns
      of Ca2+/H+-saturated sandy soil during steady saturated flow conditions.
      Instantaneous ternary H+-Ca2+-N2H5+ cation exchange using the Gaines-Thomas
      approach was combined with second-order, irreversible, kinetic chemisorption of
      exchange-phase N2H5+ ions as major retention mechanisms for N2H5+. Exchange
      mediated chemisorption is assumed to occur as chemical binding of N2H5+ ions
      located on carboxyl-group exchange sites to nearby carbonyl groups, consequently
      decreasing the effective soil cation exchange capacity (CEC). Comparison of
      simulated and observed breakthrough curves (BTCs) for concentrations of N2H5+ and
      Ca2+ ions in column effluent was used in model evaluation. The cation transport
      model with cation exchange coupled with exchange-mediated chemisorption provided
      a valid first approximation for N2H5+ transport.

PMID- 11577860
TI  - Statistical evaluation of geochemical parameter distribution in a ground water
      system contaminated with petroleum hydrocarbons.
AB  - A shallow-depth ground water area was investigated to identify the dominant
      processes governing the distribution of hydrocarbon contaminants and
      hydrogeochemical parameters. The ground water in the study site has been highly
      contaminated with petroleum hydrocarbons. A preliminary pump-and-treatment
      remediation technology was applied for 4 yr at the site. Multivariate analyses
      were applied to hydrogeochemical data obtained before and after the rainy season.
      The pump-and-treatment application, indigenous biodegradation, and mixing by
      precipitation recharge are the major factors or events involved in the
      distribution of geochemical parameters of the ground water in the study area.
      Site-specific artificial pavement also played an important role in the evolution
      of the ground water chemistry. A conventional graphical analysis method (Piper
      plot) of major ions did not effectively reveal these effects. In this study, we
      demonstrate the usefulness of multivariate analysis (factor and cluster analyses)
      using biodegradation indicator parameters, as well as major cations and anions,
      for the study of the ground water system in the hydrocarbon-contaminated site.

PMID- 11577861
TI  - Nitrate leaching beneath a containerized nursery crop receiving trickle or
      overhead irrigation.
AB  - Container production of nursery crops is intensive and a potential source of
      nitrogen release to the environment. This study was conducted to determine if
      trickle irrigation could be used by container nursery producers as an alternative
      to standard overhead irrigation to reduce nitrogen release into the environment.
      The effect of overhead irrigation and trickle irrigation on leachate nitrate N
      concentration, flow-weighted nitrate N concentration, leachate volume, and plant
      growth was investigated using containerized rhododendron (Rhododendron
      catawbiense Michx. 'Album') supplied with a controlled-release fertilizer and
      grown outdoors on top of soil-monolith lysimeters. Leachate was collected over
      two growing seasons and overwinter periods, and natural precipitation was allowed
      as a component of the system. Precipitation accounted for 69% of the water
      entering the overhead-irrigated system and 80% of the water entering the trickle
      irrigated system. Leachate from fertilized plants exceeded the USEPA limit of 10
      mg L(-1) at several times and reached a maximum of 26 mg L(-1) with trickle
      irrigation. Average annual loss of nitrate N in leachate for fertilized
      treatments was 51.8 and 60.5 kg ha(-1) for the overhead and trickle treatments,
      respectively. Average annual flow-weighted concentration of nitrate N in leachate
      of fertilized plants was 7.2 mg L(-1) for overhead irrigation and 12.7 mg L(-1)
      for trickle irrigation. Trickle irrigation did not reduce the amount of nitrate N
      leached from nursery containers when compared with overhead irrigation because
      precipitation nullified the potential benefits of reduced leaching fractions and
      irrigation inputs provided under trickle irrigation.

PMID- 11577862
TI  - Cadmium content of wheat grain from a long-term field experiment with sewage
      sludge.
AB  - Grain Cd concentrations were determined in the wheat (Triticum aestivum L.)
      cultivars Soissons, Brigadier, and Hereward grown in 1994,1996, and 1999,
      respectively, in soils of a long-term field experiment to which sewage sludges
      contaminated with Zn, Cu, Ni, or Cr had previously been added. Soil pore water
      soluble Cd and free Cd2+ increased linearly with increasing total soil Cd
      (R2=0.82 and 0.84, respectively; P<0.001). Similarly, soil pore water free Cd2+
      increased linearly with increasing soil pore water soluble Cd (R2=0.98; P<0.001).
      There was no evidence of a plateau in soil pore water Cd concentrations with
      increasing soil Cd concentrations. Grain Cd concentrations were significantly
      correlated with total soil Cd (P<0.001), soil pore water Cd (P<0.001), and free
      Cd2+ (P<0.001). A slight curvilinear relationship between grain Cd and soil Cd
      was apparent, but there was no plateau, even at the maximum soil Cd concentration
      of about 2.7 mg kg(-1). The relationship between soil pore water Cd and grain Cd
      was linear for all three cultivars. The slopes were in the order 1994 > 1996 >
      1999, with more Cd being taken up into the grain by Soissons grown in 1994, and
      least by Hereward grown in 1999. For Soissons, Cd concentration in the grain
      greater than the EU limit (0.24 mg kg(-1) dry wt.) occurred at soil Cd less than
      the current UK limit of 3 mg kg(-1) for soils receiving sewage sludge. In
      contrast, for Brigadier and Hereward, grain Cd concentrations were near to and
      less than the EU limit, respectively, at soil Cd concentrations of 3 mg kg(-1).

PMID- 11577863
TI  - A desorption-dissolution model for metal release from polluted soil under
      reductive conditions.
AB  - Various natural or provoked situations can cause significant variations in redox
      conditions that can induce reductive dissolution of soil components. When this
      happens, heavy metals that may be bound to solid phases are released. A surface
      desorption-dissolution model, which takes into account the effect of reductive
      conditions on surface site density, was established. This model is based on
      conventional reactions of surface hydroxyl groups, surface complexation reactions
      with cations and double-layer theory. The solid dissolution rate was taken into
      account, by following changes in total surface site number (i.e., cation exchange
      capacity [CEC]) under reductive conditions. This term was introduced in an
      electrostatic desorption model. Curves obtained by this calculation provided a
      good fit of experimental data as shown by statistical parameters. Experimental
      data corresponded to Pb and Cd released from a cultivated soil under reductive
      conditions induced by sodium ascorbate.

PMID- 11577864
TI  - Phosphorus export from an agricultural watershed: linking source and transport
      mechanisms.
AB  - Many source and transport factors control P loss from agricultural landscapes;
      however, little information is available on how these factors are linked at a
      watershed scale. Thus, we investigated mechanisms controlling P release from soil
      and stream sediments in relation to storm and baseflow P concentrations at four
      flumes and in the channel of an agricultural watershed. Baseflow dissolved
      reactive phosphorus (DRP) concentrations were greater at the watershed outflow
      (Flume 1; 0.042 mg L(-1)) than uppermost flume (Flume 4; 0.028 mg L(-1)).
      Conversely, DRP concentrations were greater at Flume 4 (0.304 mg L(-1)) than
      Flume 1 (0.128 mg L(-1)) during stormflow. Similar trends in total phosphorus
      (TP) concentration were also observed. During stormflow, stream P concentrations
      are controlled by overland flow-generated erosion from areas of the watershed
      coincident with high soil P. In-channel decreases in P concentration during
      stormflow were attributed to sediment deposition, resorption of P, and dilution.
      The increase in baseflow P concentrations downstream was controlled by channel
      sediments. Phosphorus sorption maximum of Flume 4 sediment (532 mg kg(-1)) was
      greater than at the outlet Flume 1 (227 mg kg(-1)). Indeed, the decrease in P
      desorption between Flumes 1 and 4 sediment (0.046 to 0.025 mg L(-1)) was similar
      to the difference in baseflow DRP between Flumes 1 and 4 (0.042 to 0.028 mg L(
      1)). This study shows that erosion, soil P concentration, and channel sediment P
      sorption properties influence streamflow DRP and TP. A better understanding of
      the spatial and temporal distribution of these processes and their connectivity
      over the landscape will aid targeting remedial practices.

PMID- 11577865
TI  - Identifying riparian sinks for watershed nitrate using soil surveys.
AB  - The capacity of riparian zones to serve as critical control locations for
      watershed nitrogen flux varies with site characteristics. Without a means to
      stratify riparian zones into different levels of ground water nitrate removal
      capacity, this variability will confound spatially explicit source-sink models of
      watershed nitrate flux and limit efforts to target riparian restoration and
      management. We examined the capability of SSURGO (1:15 840 Soil Survey Geographic
      database) map classifications (slope class, geomorphology, and/or hydric soil
      designation) to identify riparian sites with high capacity for ground water
      nitrate removal. The study focused on 100 randomly selected riparian locations in
      a variety of forested and glaciated settings within Rhode Island. Geomorphic
      settings included till, outwash, and organic/alluvial deposits. We defined
      riparian zones with "high ground water nitrate removal capacity" as field sites
      possessing both >10 m of hydric soil width and an absence of ground water surface
      seeps. SSURGO classification based on a combination of geomorphology and hydric
      soil status created two functionally distinct sets of riparian sites. More than
      75% of riparian sites classified by SSURGO as organic/alluviumhydric or as
      outwash-hydric had field attributes that suggest a high capacity for ground water
      nitrate removal. In contrast, >85% of all till sites and nonhydric outwash sites
      had field characteristics that minimize the capacity for ground water nitrate
      removal. Comparing the STATSGO and SSURGO databases for a 64000-ha watershed,
      STATSGO grossly under-represented critical riparian features. We conclude that
      the SSURGO database can provide modelers and managers with important insights
      into riparian zone nitrogen removal potential.

PMID- 11577866
TI  - Screening for organotin compounds in European landfill leachates.
AB  - As industrial chemicals, organotin compounds are predominantly applied as
      polyvinyl chloride (PVC) stabilizers and biocides. They are widely encountered in
      environmental samples and may be introduced into landfills by disposal of
      municipal solid waste or sewage sludge. In the present study, leachate samples
      were obtained from several sanitary landfill sites in Sweden, Italy, and Germany.
      These samples were analyzed by means of a highly sensitive and species-selective
      method for methyltin, butyltin, and octyltin species. In total, twelve samples
      from eight different landfill sites at various ages were investigated. The
      findings of all target compounds range between less than the limit of detection
      at 0.1 microg/L and, at maximum, 4 microg/L. Only octyltin compounds can be
      attributed to PVC products with any certainty, whereas for methyltin and butyltin
      compounds alternative and less distinct sources exist. Organotin compounds are
      subject to microbial transformation, such as dealkylation and methylation
      processes. Consequently, caution should be exercised when attributing findings to
      potential sources and deriving any predicted environmental concentrations.

PMID- 11577867
TI  - Effect of turfgrass cover and irrigation on soil mobility and dissipation of
      mefenoxam and propiconazole.
AB  - Irrigation effects on pesticide mobility have been studied, but few direct
      comparisons of pesticide mobility or persistence have been conducted on turfgrass
      versus bare soil. The interaction of irrigation practices and the presence of
      turfgrass on the mobility and dissipation of mefenoxam [N-(2,6-dimethylphenyl)-N
      (methoxyacetyl)-D-alanine methyl ester] and propiconazole (1-[[2-(2,4
      dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole) was
      studied. Sampling cylinders (20-cm diam.) were placed in either creeping
      bentgrass [Agrostis stolonifera L. var. palustris (Huds.) Farw.] or bare soil.
      Mefenoxam was applied at 770 g a.i. ha(-1) and propiconazole was applied at 1540
      g a.i. ha(-1) on 14 June 1999. Sampling cylinders were removed 2 h after
      treatment and 4,8,16, 32, and 64 days after treatment (DAT) and the cores were
      sectioned by depth. Dissipation of mefenoxam was rapid, regardless of the amount
      of surface organic matter or irrigation. The half-life (t1/2) of mefenoxam was 5
      to 6 d in turf and 7 to 8 d in bare soil. Most mefenoxam residues found in soil
      under turfgrass were in the 0- to 1-cm section at 0, 4, and 8 DAT. Residues were
      found in the 15- to 30-cm section at 4, 8, 16, 32, and 64 DAT, regardless of turf
      cover or irrigation. The t1/2 of propiconazole was 12 to 15 d in turfgrass and 29
      d in bare soil. Little movement of propiconazole was observed in either bare soil
      or turf.

PMID- 11577868
TI  - Prediction of soil organic partition coefficients by a soil leaching column
      chromatographic method.
AB  - The soil organic partition coefficient (Koc) is one of the most important
      parameters to depict the transfer and fate of a chemical in the soil-water
      system. Predicting Koc by using a chromatographic technique has been developing
      into a convenient and low-cost method. In this paper, a soil leaching column
      chromatograpy (SLCC) method employing the soil column packed with reference soil
      GSE 17201 (obtained from Bayer Landwirtschaftszentrum, Monheim, Germany) and
      methanol-water eluents was developed to predict the Koc of hydrophobic organic
      chemicals (HOCs), over a log Koc range of 4.8 orders of magnitude, from their
      capacity factors. The capacity factor with water as an eluent (k'w) could be
      obtained by linearly extrapolating capacity factors in methanol-water eluents
      (k'w) with various volume fractions of methanol (symbol in text). The important
      effects of solute activity coefficients in water on k'w and Koc were illustrated.
      Hence, the correlation between log Koc and log k'w (and log k') exists in the
      soil. The correlation coefficient (r) of the log Koc vs. log k'w correlation for
      58 apolar and polar compounds could reach 0.987, while the correlation
      coefficients of the log Koc -log k' correlations were no less than 0.968, with
      (symbol in text)ranging from 0 to 0.50. The smaller the (symbol in text), the
      higher the r. Therefore, it is recommended that the eluent of smaller (symbol in
      text), such as water, be used for accurately estimating Koc. Correspondingly, the
      r value of the log Koc -log k'w correlation on a reversed-phase Hypersil ODS
      (Thermo Hypersil, Kleinostheim, Germany) column was less than 0.940 for the same
      solutes. The SLCC method could provide a more reliable route to predict Koc
      indirectly from a correlation with k'w than the reversed-phase liquid
      chromatographic (RPLC) one.

PMID- 11577869
TI  - Toxicity of ozonated animal manure to the house fly, Musca domestica.
AB  - Swine manure slurries were ozonated at a dosage of 1 g/L and tested for their
      toxicity to the house fly (Musca domestica). The observed toxicity of ozonated
      swine manure was consistent and independent of origin of the swine manure. A dose
      (dilution) response curve was performed. A 50% dilution in the ozonated swine
      manure slurry resulted in 90% reduction in toxicity. Neither the synthetic nor
      ozonated synthetic swine manure, both of which contained higher concentrations of
      formaldehyde and three other unidentified carbonyl compounds than the ozonated
      swine manure, were toxic to the flies. Ozonated swine manure slurry was
      centrifuged and passed through a 0.45-microm filter. The liquid phase was as
      toxic as the unfiltered slurry; as such, the toxicant appears to be present in
      liquid phase. Neither ammonia, hydrogen sulfide, formaldehyde, nor other simple
      aldehydes appeared to be the toxic agent. The toxic agent appears to be a polar
      chemical compound and is concentrated in the urine. Several possible compounds
      have been identified. The toxicity of untreated and ozonated manure slurries from
      different livestock was compared. Six animal manure slurries (beef and dairy
      cattle, horse, poultry, sheep, and swine) were ozonated (dosage of 1 g/L) and
      tested for toxicity to the house fly. Ozonated dairy cattle manure slurry showed
      78% mortality after 72 h, whereas ozonated swine manure slurry achieved a 100%
      mortality rate in 48 h. Neither the unozonated dairy nor swine manure slurries,
      nor any of the other raw or ozonated manure slurries, were toxic to the flies.

PMID- 11577870
TI  - Oxidation of phenolic acid derivatives by soil and its relevance to allelopathic
      activity.
AB  - Previous studies have suggested that phenolic acids from legume green manures may
      contribute to weed control through allelopathy. The objectives of this study were
      to investigate the oxidation reactions of phenolic acids in soil and to determine
      the subsequent effects of oxidation upon phytotoxicity. Soils were reacted for 18
      h with 0.25 mmol L(-1) benzoic and cinnamic acid derivative solutions and Mn
      release from the suspension was used as a marker for phenolic acid oxidation. The
      extent of oxidation in soil suspensions was in the order of 3,4dihydroxy- > 4
      hydroxy-3-methoxy- > 4-hydroxy-approximately 2-hydroxy-substituted benzoic and
      cinnamic acids. The same ranking was observed for cyclic voltammetry peak
      currents of the cinnamic acid derivatives. This suggests that the oxidation of
      phenolic acids is controlled by the electron transfer step from the sorbed
      phenolic acid to the metal oxide. A bioassay experiment showed that the 4-hydroxy
      , 4-hydroxy-3-methoxy-, and 3,4-dihydroxy-substituted cinnamic acids were
      bioactive at 0.25 mmol L(-1) concentration. Reaction with soil for 18 h resulted
      in the elimination of bioactivity of these three cinnamic acids at the 5%
      significance level. The oxidative reactivity of phenolic acids may limit the
      potential of allelopathy as a component of an integrated weed management system.
      However, the initial phytotoxicity after soil incorporation may coincide with the
      early, critical stage of weed emergence and establishment, so that allelopathic
      phenolic acids may still play a role in weed management despite their reactivity
      in soil systems.

PMID- 11577871
TI  - Field-scale remediation of a metolachlor-contaminated spill site using zerovalent
      iron.
AB  - Pesticide spills are common occurrences at agricultural cooperatives and
      farmsteads. When inadvertent spills occur, chemicals normally beneficial can
      become point sources of ground and surface water contamination. We report results
      from a field trial where approximately 765 m3 of soil from a metolachlor [2
      chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide] spill
      site was treated with zerovalent iron (Fe0). Preliminary laboratory experiments
      confirmed metolachlor dechlorination by Fe0 in aqueous solution and that this
      process could be accelerated by adding appropriate proportions of Al2(SO4)3 or
      acetic acid (CH3COOH). The field project was initiated by moving the stockpiled,
      contaminated soil into windrows using common earth-moving equipment. The soil was
      then mixed with water (0.35-0.40 kg H2O kg(-1)) and various combinations of 5%
      Fe0 (w/w),2% Al2(SO4)3 (w/w), and 0.5% acetic acid (v/w). Windrows were covered
      with clear plastic and incubated without additional mixing for 90 d.
      Approximately every 14 d, the plastic sheeting was removed for soil sampling and
      the surface of the windrows rewetted. Metolachlor concentrations were
      significantly reduced and varied among treatments. The addition of Fe0 alone
      decreased metolachlor concentration from 1789 to 504 mg kg(-1) within 90 d,
      whereas adding Fe0 with Al2(SO4)3 and CH3COOH decreased the concentration from
      1402 to 13 mg kg(-1). These results provide evidence that zerovalent iron can be
      used for on-site, field-scale treatment of pesticide-contaminated soil.

PMID- 11577872
TI  - Coupled effects of treated effluent irrigation and wetting-drying cycles on
      transport of triazines through unsaturated soil columns.
AB  - The physical and chemical parameters controlling the movement of atrazine (6
      chloro-N2-ethyl-N4-isopropyl-l,3,5-triazine-2,4-diamine; 98.8%) and prometryn
      [N,N'-bis(1-methylethyl)-6-(methylthio)-l,3,5triazine-2,4-diamine; 99.5%] were
      investigated in columns infiltrated with treated effluent under unsaturated
      transient conditions and subjected to drying events at 22 or 60 degrees C
      followed by rewetting. Three soils varying in soil pH and texture and three
      solutions were used. The infiltrating solutions consisted of either a CaCl2
      matrix (CC), a swine waste-derived lagoon effluent (SW), or a simulated buffer
      solution (SB) representative of the element composition and pH of the SW but with
      no dissolved organic matter. Several parameters were monitored including leachate
      triazine concentrations, pH, dissolved organic carbon (DOC), inorganic carbon,
      and flow rates. Compared with CC, application of SW and SB increased column
      leachate pH, enhanced dissolution of organic carbon and particle dispersion, and
      decreased average flow rates, which allowed for increased desorption time. The
      coupled effect of these processes enhanced movement of triazines in some cases,
      with SW generally having the greatest effect. The individual effect of increased
      pH was more pronounced for prometryn (pKa=4.05) versus atrazine (pKa=1.66), and
      most dramatic for the soil with the lowest initial pH. High-temperature drying,
      which simulated intensive evaporation, further enhanced the dissolution of soil
      organic matter and the reduction in leachate flow rates with SW and SB
      applications; however, the net effect under the experimental conditions employed
      varied with soil type. Relative to low-temperature drying, high-temperature
      drying in the silty clay loam-packed columns reduced pesticide migration.

PMID- 11577873
TI  - Bioavailability of biosolids molybdenum to soybean grain.
AB  - Legumes grown in biosolids-amended soils and then fed to ruminants can represent
      problematic sources of molybdenum (Mo), but few field data are available to
      quantify the risk. We used a set of fields amended to high cumulative biosolids
      Mo loads (>18 kg ha(-1)) over 27 yr to generate additional data. Soybean [Glycine
      max (L.) Merr.] was grown on 29 fields (pH values>6.8) amended to a wide range of
      soil Mo loads. Soybean grain harvested from each field was analyzed for Mo and
      the concentrations regressed against soil Mo loads estimated from actual soil Mo
      concentrations in the 0- to 15-cm depth. Slopes of such linear regressions
      represent uptake coefficients (UC values) used by the USEPA to assess risk of
      biosolids Mo to ruminants fed forage grown on biosolids-amended land. The UC
      value for all 29 fields was estimated as 1.66, which agrees with the few soybean
      grain data in the literature. The UC value, however, is well below a conservative
      UC value of 4, recently recommended for all fresh legume materials fed to cattle.
      Soybean grain can contain high concentrations of Mo (>10 mg kg(-1)) and have low
      (<2:1) Cu to Mo ratios, which can exacerbate molybdenosis problems in cattle.
      However, soybean grain normally constitutes only -10% of dairy cattle diet, and
      other constituents (e.g., corn grain, stover, mineral supplements) are
      sufficient, or can be manipulated, to control molybdenosis.

PMID- 11577874
TI  - Ryegrass cover crop effects on nitrate leaching in spring barley fertilized with
      15NH415NO3.
AB  - Cover crops are a management option to reduce NO3 leaching under cereal grain
      production. A 2-yr field lysimeter study was established in Uppsala, Sweden, to
      evaluate the effect of a perennial ryegrass (Lolium perenne L.) cover crop
      interseeded in barley (Hordeum vulgare L.) on NO3-N leaching and availability of
      N to the main crop. Barley and ryegrass or barley alone were seeded in mid-May
      1992, in lysimeters (03-m diam. x 1.2-m depth) of an undisturbed, well-drained,
      sandy loam soil. Fertilizer N was applied at the same time as labeled l5NH415NO3
      (10 atom % 15N) at a rate of 100 kg N ha(-1). In 1993, barley was reseeded in May
      in the lysimeters but with nonlabeled NH4NO3 and no cover crop (previous year's
      cover crop incorporated just prior to seeding). Barley yields and total and
      fertilizer N uptake in Year 1 (1992) were unaffected by cover crop. Total
      aboveground N uptake by the ryegrass was 28 kg ha(-1) at the time of
      incorporation the following spring. Recovery of fertilizer-derived N in May 1993
      was about 100%; 53% in soil, 46% in barley, <2% in ryegrass, and negligible
      amounts in leachate. In May 1994, the corresponding figures were: 32% in soil,
      <3% in barley, and, again, negligible amounts in leachate. The cover crop reduced
      concentrations of NO3-N in the leachate considerably (<5 mg L(-1), compared with
      10 to 18 mg L(-1) without cover crop) at most sampling times from November 1992
      to April 1994, and reduced the total amount of NO3-N leached (22 compared with 8
      kg ha(-1)).

PMID- 11577875
TI  - Distribution and movement of sludge-derived trace metals in selected Nigerian
      soils.
AB  - Use of metal-rich sewage sludge as soil fertilizer may result in trace- metal
      contamination of soils. This study was conducted to evaluate the effects of long
      term sludge application on trace-metal (Zn, Cu, Pb, and Ni) distribution and
      potential bioavailability in Nigerian soils under a tropical wet-dry climate.
      Total metal analyses, sequential chemical fractionation, and DTPA extractions
      were carried out on samples of control and sludge-amended pedons in Nigeria (a
      Rhodic Kandiustult and two Rhodic Kandiustalfs from Nigeria, respectively). The
      sewage sludge applied to the soils contained higher levels of Zn and Cu than Pb
      and Ni. The control pedon contained low levels of all four metals. Soil
      enrichment factors (EF) were calculated for each metal in the sludge-amended
      pedons. Compared with the control soil, the sludge-amended pedons showed elevated
      levels of Zn and Cu, reflecting the trace-metal composition of the sewage sludge.
      Zinc and Cu in the sludge-amended soils were strongly enriched at all depths in
      the profile, indicating that they had moved below the zone of sludge application.
      The sequential extraction and DTPA analyses indicated that the sludge-amended
      soils contained more readily extractable and bioavailable metal ions than the
      unamended soil.

PMID- 11577876
TI  - Degradation of biomacromolecules during high-rate composting of wheat straw
      amended feces.
AB  - Pig (Sus scrofa) feces, separately collected and amended with wheat straw, was
      composted in a tunnel reactor connected with a cooler. The composting process was
      monitored for 4 wk and the degradation of organic matter was studied by two
      chemical extraction methods, 13C cross polarization magic angle spinning (CPMAS)
      nuclear magnetic resonance (NMR) and pyrolysis gas chromatography-mass
      spectrometry (GC-MS). Wet-chemical extraction methods were not adequate to study
      the degradation of specific organic compounds as the extraction reagents did not
      give selective separation of hemicellulose, cellulose, proteins, and lignins. A
      new method was proposed to calculate the contribution of four biomacromolecules
      (aliphatics, proteins, polysaccharides, and lignin) from the 13C CPMAS NMR
      spectrum. Pyrolysis GC-MS allowed identification of the composition of the
      biomacromolecules. The biomacromolecules showed different rates of degradation
      during composting. High initial degradation rates of aliphatics, hemicellulose,
      and proteins were observed, where aliphatics were completely degraded and
      hemicellulose and proteins were partly recalcitrant during the four weeks of
      composting. The degradation rate of cellulose was much lower and degradation was
      not completed within the four weeks of composting. Lignin was not degraded during
      the thermophilic stage of composting but started to degrade slowly during the
      mesophilic stage. A combination of 13C CPMAS NMR and pyrolysis GC-MS gave good
      qualitative and semiquantitative assessments of the degradation of
      biomacromolecules during composting.

PMID- 11577878
TI  - Manure phosphorus extractability as affected by aluminum- and iron by-products
      and aerobic composting.
AB  - Shifts in manure phosphorus (P) chemical forms and pool sizes induced by water
      treatment residuals and industrial mineral by-products are largely undefined. We
      conducted a manure P fractionation study to determine mechanisms of reduction of
      dissolved reactive phosphorus (DRP) in poultry manure upon mineral by-product
      additions. The effects of composting on the P immobilization efficacy of the by
      products were determined using laboratory self-heating composting simulators. The
      mineral by-products included an aluminum-water treatment residual (Al-WTR) and an
      iron-rich titanium-processing by-product. The noncomposted manure averaged 0.11 g
      g(-1) of total P as DRP forms. The by-products significantly reduced manure DRP,
      by an average of 39 and 48% in the Al- and the Fe-treated manure, respectively.
      The by-products also reduced the 0.5 M NH4F-extractable phosphorus (FEP)
      fraction. Shifts in P forms between FEP and 0.1 M NaOH-extractable phosphorus
      (SHEP) depended upon the Al and Fe contents of the by-products while the combined
      FEP + SHEP pool remained constant. Phosphate sorption measurements supported the
      observations that the Fe-rich by-product was more effective at reducing manure
      DRP and enhancing the formation of SHEP forms at the expense of FEP than the Al
      WTR. Composting had no effect on the efficacy of either by-product to reduce DRP.
      Potential mechanisms of enhanced P stabilization in treated manure upon
      composting included chemical shifts from the DRP and FEP fractions to the citrate
      bicarbonate-dithionite extractable P fraction. Thus, the choice of P
      immobilization agents affected the stability of immobilized P forms and should be
      taken into consideration in developing manure processing and nutrient
      stabilization methods.

PMID- 11577877
TI  - Enzymatic characterization of organic phosphorus in animal manure.
AB  - Information on the forms of P present in animal manure may improve our ability to
      manage manure P. In most investigations of manure P composition, only inorganic
      and total P are determined, and the difference between them is assigned as
      organic P. In this study, we explored the possibility of identifying and
      quantifying more specific organic P forms in animal manure with orthophosphate
      releasing enzymes. Pig (Sus scrofa) manure and cattle (Bos taurus) manure were
      first sequentially fractionated into water-soluble P, NaHCO3-soluble P, NaOH
      soluble P, HCl-soluble P, and residual P. The fractions were separately incubated
      with wheat phytase, alkaline phosphatase, nuclease P1, nucleotide
      pyrophosphatase, or their combinations. The released orthophosphate was
      determined by a molybdate blue method. Part of the organic P in those fractions
      could be identified by the enzymatic treatments as phytate (i.e., 39% for pig
      manure and 17% for cattle manure in water-soluble organic P), simple
      phosphomonoesters (i.e., 43% for pig manure and 15% for cattle manure in NaOH
      soluble organic P), nucleotide-like phosphodiesters (2-12%), and nucleotide
      pyrophosphate (0-4%). Our data indicate that the enzymatic treatment is an
      effective approach to identify and quantify the organic P forms present in animal
      manures.

PMID- 11577879
TI  - Leachate chemistry of field-weathered spent mushroom substrate.
AB  - Passive leaching by rainfall and snowmelt is a popular method to treat piles of
      spent mushroom substrate (SMS) before its reuse. During this field weathering
      process, leachate percolates into the underlying soils. A field study was
      conducted to examine the chemistry of SMS leachate and effects of infiltration.
      Two SMS piles were deposited (90 and 150 cm in height) over a Typic Hapludult and
      weathered for 24 mo. Leachate was collected biweekly using passive capillary
      samplers. The SMS leachate contained high concentrations of dissolved organic
      carbon (DOC; 0.8-11.0 g L(-1)), dissolved organic nitrogen (DON; 0.1-2 g L(-1)),
      and inorganic salts. The pH, electrical conductivity, and acid neutralizing
      capacity were 6.6 to 9.0, 21 to 66 ds m(-1), and 10 to 75 mmolc L(-1),
      respectively. Inorganic chemistry of the leachate was dominated by K+, Cl-, and
      SO24-. Leachate DOC was predominantly low molecular weight (<1000 Da) organic
      acids. During 2 yr of weathering, the 90-cm SMS pile released (per cubic meter of
      SMS) 3.0 kg of DOC, 1.6 kg of dissolved N, and 26.6 kg of inorganic salts. The
      150-cm pile released (per cubic meter of SMS) 2.8 kg of DOC, 0.7 kg of dissolved
      N, and 13.6 kg of inorganic salts. The 150 cm pile retained more water and
      exhibited lower net nitrification compared with the 90-cm pile. The top 90 cm of
      soil retained 20 to 89% of the leachate solutes. Weathering of SMS in piles of 90
      cm depth or greater may adversely affect ground water quality.

PMID- 11577880
TI  - Trace element removal from coal ash leachate by a 10-year-old constructed
      wetland.
AB  - This study investigated the ability of a 10-yr-old constructed wetland to treat
      metal-contaminated leachate emanating from a coal ash pile at the Widows Creek
      electric utility, Alabama (USA). The two vegetated cells, which were dominated by
      cattail (Typha latifolia L.) and soft rush (Juncus effusus L.), were very
      effective at removing Fe and Cd from the wastewater, but less efficient for Zn,
      S, B, and Mn. The concentrations were decreased by up to 99% for Fe, 91% for Cd,
      63% for Zn, 61% for S, 58% for Mn, and 50% for B. Higher pH levels (>6) in
      standing water substantially improved the removing efficiency of the wetland for
      Mn only. The belowground tissues of both cattail and soft rush had high
      concentrations of all elements; only for Mn, however, did the concentration in
      the shoots exceed those in the belowground tissues. The concentrations of trace
      elements in fallen litter were higher than in the living shoots, but lower than
      in the belowground tissues. The trace element accumulation in the plants
      accounted for less than 2.5% of the annual loading of each trace element into the
      wetland. The sediments were the primary sinks for the elements removed from the
      wastewater. Except for Mn, the concentrations of trace elements in the upper
      layer (0-5 cm) of the sediment profile tended to be higher than the lower layers
      (5-10 and 10-15 cm). We conclude that constructed wetlands are still able to
      efficiently remove metals in the long term (i.e.,>10 yr after construction).

PMID- 11577881
TI  - Nutrient attenuation by a riparian wetland during natural and artificial runoff
      events.
AB  - Due to chronic nutrient enrichment of surface water, wetlands adjacent to land
      managed with fertilizer have been studied to determine their role in nutrient
      dynamics. We sampled golf course runoff and determined the loads of NO3- and PO4(
      3) transported during storms and the attenuation of those loads when runoff
      passed through a riparian wetland. All sampled storm events contained NO3- (2 to
      1470 g NO3-N per event) and PO4(-3) (1 to 4156 g PO4-P per event). Extensive
      nutrient attenuation occurred when water passed through the riparian wetland. In
      11 events, NO3- and PO4(-3) attenuation averaged 80 and 74%, respectively. In
      subsequent experiments, we created a stream of water flowing into the wetland and
      amended it with NO3-, PO4(-3) and Br-, creating an artificial runoff event. The
      experiments were conducted using conditions similar to those of natural runoff
      events. We observed rapid and complete attenuation of PO4(-3) immediately after
      runoff water infiltrated into the wetland subsurface. No PO4(-3) was observed in
      discharge from the wetland. Nitrate attenuation occurred following a lag phase of
      several hours that was probably due to reactivation of denitrifying enzymes.
      Nitrate attenuation was initially less than 60% but increased to 100% in all
      experiments. We observed extensive dilution of runoff water in the wetland
      subsurface indicating mixing with pre-event ground water in the wetland. The
      results indicated that intermittent inputs of NO3- and PO4(-3) could be
      successfully attenuated in the wetland on the time scale of natural storm events.

PMID- 11577882
TI  - Mechanisms of nutrient attenuation in a subsurface flow riparian wetland.
AB  - Riparian wetlands are transition zones between terrestrial and aquatic
      environments that have the potential to serve as nutrient filters for surface and
      ground water due to their topographic location. We investigated a riparian
      wetland that had been receiving intermittent inputs of NO3- and PO4(3-) during
      storm runoff events to determine the mechanisms of nutrient attenuation in the
      wetland soils. Few studies have shown whether infrequent pulses of NO3- are
      sufficient to maintain substantial denitrifying communities. Denitrification
      rates were highest at the upstream side of the wetland where nutrient-rich runoff
      first enters the wetland (17-58 microg N2O-N kg soil(-1) h(-1)) and decreased
      further into the wetland. Carbon limitation for denitrification was minor in the
      wetland soils. Samples not amended with dextrose had 75% of the denitrification
      rate of samples with excess dextrose C. Phosphate sorption isotherms suggested
      that the wetland soils had a high capacity for P retention. The calculated soil
      PO4(3-) concentration that would yield an equilibrium aqueous P04(3-)
      concentration of 0.05 mg P L(-1) was found to be 100 times greater than the soil
      PO4(3-) concentration at the time of sampling. This indicated that the wetland
      could retain a large additional mass of PO4(3-) without increasing the dissolved
      P04(3-) concentrations above USEPA recommended levels for lentic waters. These
      results demonstrated that denitrification can be substantial in systems receiving
      pulsed NO3- inputs and that sorption could account for extensive PO4(3-)
      attenuation observed at this site.

PMID- 11577883
TI  - Phosphorus loading in the Frome catchment, UK: seasonal refinement of the
      coefficient modeling approach.
AB  - This paper describes the results of an export coefficient modeling approach to
      predict total phosphorus (TP) loading in the Frome catchment, Dorset, UK from
      point and diffuse sources on a seasonal (monthly) basis in 1998 and on an annual
      basis for 1990-1998. The model predicted an annual TP load of 25 605 kg yr(-1),
      compared with an observed (measured) value of 23400 kg yr(-1). Monthly loads
      calculated using the export coefficient model agreed well with monthly observed
      values except in months of variable discharge, when observed values were low,
      probably due to infrequent, and therefore unrepresentative, sampling. Comparison
      between filterable reactive phosphorus (FRP) and TP concentrations observed in
      the period 1990-1997 showed that trends in FRP could be estimated from trends in
      TP. A sensitivity analysis (varying individual export coefficients by +/-10%)
      showed that sewage treatment works (STWs) (3.5%), tilled land (2.7%), meadow
      verge-seminatural (1.0%), and mown and grazed turf (0.6%) had the most
      significant effect (percent difference from base contribution) on model
      prediction. The model was also used to estimate the effect of phosphorus
      stripping at STWs in order to comply with a pending change in the European Union
      wastewater directive. Theoretical reduction of TP from the largest STW in the
      catchment gave a predicted reduction in TP loading of 2174 kg yr(-1). This
      illustrates the value of this seasonal export coefficient model as a practical
      management tool.

PMID- 11577884
TI  - Aluminum output fluxes from forest ecosystems in Europe: a regional assessment.
AB  - Data from 89 forested catchments and plots across Europe were used to define
      empirical relationships between aluminum leaching and input fluxes of major ions,
      output fluxes of major ions, ecosystem parameters such as soil pH, and
      combinations of these. Forests that release dissolved Al to seepage or surface
      waters are located primarily in areas receiving the highest loading of acid rain,
      and the output flux of Al shows the highest correlations to the throughfall flux
      of inorganic nitrogen, the output fluxes of NO3-, H+, and SO4(2-), and the
      mineral soil pH. If the speciation of Al is taken to be Al3+ (an overestimate),
      Al is released in a nearly 1:1 molar charge ratio with the sum of NO3- and SO4(2
      ) in runoff or seepage water over a wide range of basepoor bedrock types and acid
      deposition across Europe. The empirical data point to a threshold range of N
      deposition of 80 to 150 mmolc N m(-2) yr(-1) and a (less clearly defined) range
      of S deposition of 100 to 200 mmolc SO4(-2) m(-2) yr(-1) above which Al released
      from forests exceeds 100 mmolc Al m(-2) yr(-1). Within this threshold range, the
      sites that release little or no dissolved Al are those that continue to
      assimilate input N and/or have high soil pH (>4.5).

PMID- 11577885
TI  - Chloride persistence in a deiced access road drainage system.
AB  - Three years of field data, classical linear reservoir theory, and a new
      dissolution model confirm the hypothesis that residual chloride from highway
      deicing applications dissolves into precipitation throughout the year. The
      measured input includes 52 storm hyetographs and logs of salt and premix
      applications on an access road with a closed drainage system subject to runoff,
      interflow, and baseflow. The output data feature discharge and conductivity in an
      outlet weir measured continuously from February 1998 to May 2000. Individual
      storm hydrographs and pollutographs yield calibrated first flush dissolved
      chloride concentrations and residual solid chloride loads that persist at
      appreciable levels over the entire period of record. The storm calibrations imply
      a source strength w of 2.01 x 10(-6) s(-1) that accurately models chloride
      dissolution kinetics through three salt seasons on the access road. This w rests
      on physically plausible values for the depression storage depth zeta (3 mm) and
      porosity n (0.40) that store the residual chloride.

PMID- 11577886
TI  - Cesium-134 as a tracer to study particle transport processes within a small
      catchment with a buffer zone.
AB  - The purpose of the study is to use soil particles labeled with the radioactive
      tracer cesium-134 (134Cs) as a method for studying soil erosion and sedimentation
      pattern within a small catchment with buffer zones. Cesium is adsorbed to soil
      particles, and by measuring changes in the 134Cs activity on the soil surface,
      erosion, sedimentation, and pathways for particles can be traced. A harrowed area
      was surface-contaminated with 134CsCl, while the buffer zone was left
      uncontaminated. A grid net in the tilled plot and buffer zone was established for
      in situ measurements of the 134Cs activity after major runoff events from October
      1993 to May 1996. In addition, 134Cs activity and suspended solids in runoff were
      followed during the events. At the end of the experiment, the vertical
      distribution of 134Cs in soil profiles and uptake of 134Cs in vegetation within
      the buffer zone were determined. At the end of the experiment, about 54% of the
      applied tracer remained at the soil surface. Surface soil erosion occurred
      relatively uniformly across the hillslope due to sheet flow. Most of the tracer
      was transported vertically into the soil profile, probably during the first heavy
      rainfall 3 wk after application when the soil was newly tilled. Sedimentation
      occurred in the upper part of the buffer zone. The correlation between suspended
      particles in runoff and 134Cs activity was good (R2=0.76). The study also
      demonstrates the benefit of utilizing 134Cs2+ tracer for investigating transport
      pathways for contaminated partic1les within a hillslope system without disturbing
      the surface soil system.

PMID- 11577887
TI  - Phosphorus and ammonium concentrations in surface runoff from grasslands
      fertilized with broiler litter.
AB  - Application of broiler (Gallus gallus domesticus) litter to grasslands can
      increase ammonium (NH4-N) and dissolved reactive phosphorus (DRP) concentrations
      in surface runoff, but it is not known for how long after a broiler litter
      application that these concentrations remain elevated. This long-term study was
      conducted to measure NH4-N and DRP in surface runoff from grasslands fertilized
      with broiler litter. Six 0.75-ha, fescue (Festuca arundinacea Schreb.
      )bermudagrass [Cynodon dactylon (L.) Pers.] paddocks received broiler litter
      applications in the spring and fall of 1995-1996 and only inorganic fertilizer N
      in the spring of 1997-1998. Surface runoff from each paddock was measured and
      analyzed for NH4-N and DRP. Broiler litter increased flow-weighted NH4-N and DRP
      concentrations from background values of 0.5 and 0.4 mg L(-1), respectively, to
      values > 18 mg L(-1) in a runoff event that took place immediately after the
      third application. Ammonium concentrations decreased rapidly after an application
      and were not strongly related to time after application or runoff volume. In
      contrast, DRP concentrations tended to decrease more slowly, reaching values near
      1 mg L(-1) by 19 mo after the last application. Dissolved reactive P
      concentrations decreased linearly with the natural logarithm of days after
      application (p<0.03), and increased linearly with the natural logarithm of runoff
      volume (p<0.0001).

PMID- 11577888
TI  - Phosphorus losses from grasslands fertilized with broiler litter: EPIC
      simulations.
AB  - Broiler litter, a mixture of poultry excreta and bedding material, is commonly
      used to fertilize grasslands in the southeastern USA. Previous work has shown
      that under certain situations, application of broiler (Gallus gallus domesticus)
      litter to grasslands may lead to elevated levels of phosphorus (P) in surface
      runoff. The EPIC simulation model may be a useful tool to identify those
      situations. This work was conducted to evaluate EPIC's ability to simulate event
      and annual runoff volume and losses of dissolved reactive phosphorus (DRP) from
      tall fescue (Festuca arundinacea Schreb.)-bermudagrass [Cynodon dactylon (L.)
      Pers.] paddocks fertilized with broiler litter. The EPIC simulations of event
      runoff volume showed a trend toward underestimation, particularly for runoff
      events >30 mm. On an annual basis, EPIC also tended to underestimate runoff,
      especially at runoff volumes > 100 mm. Both event and annual runoff estimations
      were strongly associated with observed values, indicating that model calibration
      could improve the simulation of surface runoff volume. The relationship between
      simulated and observed values of DRP loss was relatively poor on an event basis
      (r=0.65), but was stronger (r=0.75) on an annual basis. In general, EPIC tended
      to underestimate annual DRP losses. This underestimation was apparently caused by
      the lack of an explicit mechanism to model broiler litter on the soil surface.
      These results suggested that additional work on the EPIC P submodel would be
      warranted to improve its simulation of surface application of broiler litter to
      grasslands.

PMID- 11577889
TI  - Herbicide and nutrient transport from an irrigation district into the South
      Saskatchewan River.
AB  - Pesticides and nutrients can be transported from treated agricultural land in
      irrigation runoff and thus can affect the quality of receiving waters. A 3-yr
      study was carried out to assess possible detrimental effects on the downstream
      water quality of the South Saskatchewan River due to herbicide and plant nutrient
      inputs via drainage water from an irrigation district. Automated water samplers
      and flow monitors were used to intensively sample the drainage water and to
      monitor daily flows in two major drainage ditches, which drained approximately
      40% of the flood-irrigated land within the irrigation district. Over three years,
      there were no detectable inputs of ethalfluralin into the river and those of
      trifluralin were less than 0.002% of the amount applied to flood-irrigated
      fields. Inputs of MCPA, bromoxynil, dicamba and mecoprop were 0.06% or less of
      the amounts applied, whereas that for clopyralid was 0.31%. The relatively higher
      input (1.4%) of 2,4-D to the river was probably due its presence in the
      irrigation water. Corresponding inputs of P (as total P) and N (as nitrate plus
      ammonia) were 2.2 and 1.9% of applied fertilizer, respectively. Due to dilution
      of the drainage water in the river, maximum daily herbicide (with the exception
      of 2,4-D) and nutrient loadings to the river would not have resulted in
      significant concentration increases in the river water. There was no consistent
      remedial effect on herbicides entering the river due to passage of the drainage
      water through a natural wetland. In contrast, a considerable portion of the
      nutrients entering the river originated from the wetland.

PMID- 11577890
TI  - Runoff loss of pesticides and soil: a comparison between vegetative mulch and
      plastic mulch in vegetable production systems.
AB  - Current vegetable production systems use polyethylene (plastic) mulch and require
      multiple applications of agrochemicals. During rain events, runoff from vegetable
      production is enhanced because 50 to 75% of the field is covered with an
      impervious surface. This study was conducted to quantify off-site movement of
      soil and pesticides with runoff from tomato (Lycopersicon esculentum Mill.) plots
      containing polyethylene mulch and a vegetative mulch, hairy vetch (Vicia villosa
      Roth). Side-by-side field plots were instrumented with automated flow meters and
      samplers to measure and collect runoff, which was filtered, extracted, and
      analyzed to determine soil and pesticide loss. Seasonal losses of two to four
      times more water and at least three times as much sediment were observed from
      plots with polyethvlene mulch (55.4 to 146 L m(-2) and 247 to 535 g m(-2),
      respectively) versus plots with hairy vetch residue (13.7 to 75.7 L m(-2) and
      32.8 to 118 g m(-2), respectively). Geometric means (+/-standard deviation) of
      total pesticide loads for chlorothalonil (tetrachloroisophthalonitrile) and alpha
      and beta-endosulfan (6,7,8,9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro6,9-methano
      2,4,3-benzodioxathiepin 3-oxide) for a runoff event were 19, 6, and 9 times
      greater from polyethylene (800+/-4.6, 17.6+/-3.9, and 39.1+/-4.9 microg m(-2),
      respectively) than from hairy vetch mulch plots (42+/-6.0, 2.8+/-5.0, and 4.3+/
      4.6 microg m(-2), respectively) due to greater concentrations and larger runoff
      volumes. The increased runoff volume, soil loss, and off-site loading of
      pesticides measured in runoff from the polyethylene mulch suggests that this
      management practice is less sustainable and may have a harmful effect on the
      environment.

PMID- 11577891
TI  - Management practice effects on phosphorus losses in runoff in corn production
      systems.
AB  - Phosphorus losses in runoff from cropland can contribute to nonpoint-source
      pollution of surface waters. Management practices in corn (Zea mays L.)
      production systems may influence P losses. Field experiments with treatments
      including differing soil test P levels, tillage and manure application
      combinations, and manure and biosolids application histories were used to assess
      these management practice effects on P losses. Runoff from simulated rainfall (76
      mm h(-1)) was collected from 0.83-m2 areas for 1 h after rainfall initiation and
      analyzed for dissolved reactive P (DRP), bioavailable P, total P (TP), and
      sediment. In no-till corn, both DRP concentration and load increased as Bray P1
      soil test (STP) increased from 8 to 62 mg kg(-1). A 5-yr history of manure or
      biosolids application greatly increased STP and DRP concentrations in runoff. The
      5-yr manure treatment had higher DRP concentration but lower DRP load than the 5
      yr biosolids treatment, probably due to residue accumulation and lower runoff in
      the manure treatment. Studies of tillage and manure application effects on P
      losses showed that tillage to incorporate manure generally lowered runoff DRP
      concentration but increased TP concentration and loads due to increased sediment
      loss. Management practices have a major influence on P losses in runoff in corn
      production systems that may overshadow the effects of STP alone. Results from
      this work, showing that some practices may have opposite effects on DRP vs. TP
      losses, emphasize the need to design management recommendations to minimize
      losses of those P forms with the greatest pollution potential.

PMID- 11577892
TI  - Using phosphorus concentration in the soil solution to predict phosphorus
      desorption to water.
AB  - The growing concerns about water eutrophication have made it urgent to restrict
      losses of phosphorus (P) from agricultural soils and to develop methods for
      predicting such losses. In this work, we used the paradigm of P sorption
      desorption curves to confirm the hypothesis that the amount of dissolved reactive
      phosphorus (DRP) released to a dilute electrolyte tends to be proportional to the
      concentration of DRP in the soil solution raised to a power that decreases with
      increasing solution to soil ratio (W). The hypothesis was tested for a group of
      12 widely ranging European agricultural soils fertilized with P in excess of crop
      needs. Phosphorus desorption was studied under near-static and turbulent
      conditions in laboratory experiments. The concentration of DRP in the 1:1 soil to
      water extract (P1:1) was used as a proxy for the DRP concentration in the soil
      solution. The amount of desorbed P was found to be correlated with P1:1 raised to
      a power that decreased from 0.7 to 0.9 at W=100 to 0.2 to 0.4 at W=10 000.
      Correlation was not improved by introducing additional variables related to P
      sorption-desorption properties. Olsen P was found to be of lower predictive value
      than P1:1. Also, the index of degree of soil saturation with phosphorus (DSSP)
      based on oxalate extraction failed to predict P desorption. The fact that P1:1
      seemingly predicts P desorption accurately for a wide range of soils makes it
      potentially useful in areas of high soil diversity.

PMID- 11577893
TI  - Differentiating nonpoint sources of deisopropylatrazine in surface water using
      discrimination diagrams.
AB  - Pesticide degradates account for a significant portion of the pesticide load in
      surface water. Because pesticides with similar structures may degrade to the same
      degradate, it is important to distinguish between different sources of parent
      compounds that have different regulatory and environmental implications. A
      discrimination diagram, which is a sample plot of chemical data that
      differentiates between different parent compounds, was used for the first time to
      distinguish whether sources other than atrazine (6-chloro-N2-ethyl-N4-isopropyl
      1,3,5-triazine-2,4-diamine) contributed the chlorinated degradate,
      deisopropylatrazine (DIA; 6-chloro-N-ethyl-1,3,5-triazine-2,4-diamine) to the
      Iroquois and Delaware Rivers. The concentration ratio of deisopropylatrazine to
      deethylatrazine [6-chloro-N-(1-methylethyl)1,3,5-triazine-2,4-diamine], called
      the D2R, was used to discriminate atrazine as a source of DIA from other parent
      sources, such as cyanazine (2-[[4-chloro-6-(ethylamino)-1,3,5-triazin-2-yl]amino]
      2-methylpropionitrile) and simazine (6-chloro-N,N'-diethyl-1,3,5-triazine
      2,4diamine). The ratio of atrazine to cyanazine (ACR) used in conjunction with
      the D2R showed that after atrazine, cyanazine was the main contributor of DIA in
      surface water. The D2R also showed that cyanazine, and to a much lesser extent
      simazine, contributed a considerable amount (approximately 40%) of the DIA that
      was transported during the flood of the Mississippi River in 1993. The D2R may
      continue to be a useful discriminator in determining changes in the nonpoint
      sources of DIA in surface water as cyanazine is currently being removed from the
      market.

PMID- 11577894
TI  - Pesticide applications of copper on perennial crops in California, 1993 to 1998.
AB  - Inorganic copper is used as a broad-spectrum fungicide and bacteriocide on a
      variety of agricultural crops. After application, the copper residue typically
      accumulates in the upper 15 cm of soil. Data from the California Pesticide Use
      Reports were used to estimate the augmentation of copper in the soil that
      resulted from pesticide applications for the six years from 1993 to 1998 on 12
      crops that are grown without rotation. The estimated mean mg Cu kg(-1) soil added
      to the upper 15 cm during the six years was the following: walnut (Juglans regia
      L.), 28; peach [Prunus persica (L.) Batsch var. persica], 22; nectarine
      [Prunuspersica (L.) Batsch var. nucipersica (Suckow) C.K. Schneid], 19; cherry
      (Pseudolmedia oxyphyllaria Donn. Sm.), 18; rice (Orvza sativa L.), 16; apricot
      (Prunus armeniaca L.), 11; orange [Citrus sinensis (L.) Osbeck) and plum (Prunus
      domestica L. subsp. domestica ), 9; lemon [Citrus limon (L.) Burm.f.] and almond
      [Prunus dulcis (Mill.) D.A. Webb], 6; pear (Pyrus communis L.), 4; and grape
      (Vitis vinifera L.), 3. In addition, for the first five of these crops, we
      estimated the area that was treated with each level of kg Cu ha(-1). For example,
      for walnut orchards, we estimated that 12 500 ha, or 17% of the planted area, was
      treated with a quantity of Cu that would increase the total concentration of Cu
      in the upper 15 cm of soil by at least 50 mg Cu kg(-1) soil. A comparison of the
      amount of Cu per unit planted area that was applied in the first and second half
      of the study indicated that the intensity of copper use is either relatively
      constant or increasing, depending on the crop. The findings are discussed in
      relation to the potential effect of continued long-term use of Cu pesticides on
      soil sustainability.

PMID- 11577896
TI  - Comparison between the Fourier and Wavelet methods of spectral analysis applied
      to stationary and nonstationary heart period data.
AB  - The aim of this study was to assess the error made by violating the assumption of
      stationarity when using Fourier analysis for spectral decomposition of heart
      period power. A comparison was made between using Fourier and Wavelet analysis
      (the latter being a relatively new method without the assumption of
      stationarity). Both methods were compared separately for stationary and
      nonstationary segments. An ambulatory device was used to measure the heart period
      data of 40 young and healthy participants during a psychological stress task and
      during periods of rest. Surprisingly small differences (<1%) were found between
      the results of both methods, with differences being slightly larger for the
      nonstationary segments. It is concluded that both methods perform almost
      identically for computation of heart period power values. Thus, the Wavelet
      method is only superior for analyzing heart period data when additional analyses
      in the time-frequency domain are required.

PMID- 11577895
TI  - Contrasting nitrate adsorption in Andisols of two coffee plantations in Costa
      Rica.
AB  - Fertilizer use in coffee plantations is a suspected cause of rising ground water
      nitrate concentrations in the ground water-dependent Central Valley of Costa
      Rica. Nitrate adsorption was evaluated beneath two coffee (Coffea arabica L.)
      plantations in the Central Valley. Previous work at one site had identified
      unsaturated zone nitrate retardation relative to a tritium tracer. Differences in
      nitrate adsorption were assessed in cores to 4 m depth in Andisols at this and
      one other plantation using differences in KCl- and water-extractable nitrate as
      an index. Significant adsorption was confirmed at the site of the previous tracer
      test, but not at the second site. Anion exchange capacity, X-ray diffraction
      data, extractable Al and Si, and soil pH in NaF corroborated that differences in
      adsorption characteristics were related to subtle differences in clay mineralogy.
      Soils at the site with significant nitrate adsorption showed an Al-rich allophane
      clay content compared with a more weathered, Si-rich allophane and halloysite
      clay mineral content at the site with negligible adsorption. At the site with
      significant nitrate adsorption, nitrate occupied less than 10% of the total anion
      adsorption capacity, suggesting that adsorption may provide long-term potential
      for mitigation or delay of nitrate leaching. Evaluation of nitrate sorption
      potential of soil at local and landscape scales would be useful in development of
      nitrogen management practices to reduce nitrate leaching to ground water.

PMID- 11577897
TI  - Nonspatial intermodal selective attention is mediated by sensory brain areas:
      evidence from event-related potentials.
AB  - The present study focuses on the question of whether inter- and intramodal forms
      of attention are reflected in activation of the same or different brain areas.
      ERPs were recorded while subjects were presented a random sequence of visual and
      auditory stimuli. They were instructed to attend to nonspatial attributes of
      either auditory or visual stimuli and to detect occasional target stimuli within
      the attended channel. An occipital selection negativity was found for intramodal
      attention to visual stimuli. Visual intermodal attention was also manifested in a
      similar negativity. A symmetrical dipole pair in the medial inferior occipital
      areas could account for the intramodal effects. Dipole pairs for the intermodal
      attention effect had a slightly more posterior location compared to the dipole
      pair for the intramodal effect. Auditory intermodal attention was manifested in
      an early enhanced negativity overlapping with the N1 and P2 components, which was
      localized using a symmetrical dipole pair in the lateral auditory cortex. The
      onset of the intramodal attention effect was somewhat later (around 200 ms), and
      was reflected in a frontal processing negativity. The present results indicate
      that intra- and intermodal forms of attention were indeed similar for visual
      stimuli. Auditory data suggest the involvement of multiple brain areas.

PMID- 11577898
TI  - Error-related brain potentials are differentially related to awareness of
      response errors: evidence from an antisaccade task.
AB  - The error negativity (Ne/ERN) and error positivity (Pe) are two components of the
      event-related brain potential (ERP) that are associated with action monitoring
      and error detection. To investigate the relation between error processing and
      conscious self-monitoring of behavior, the present experiment examined whether an
      Ne and Pe are observed after response errors of which participants are unaware.
      Ne and Pe measures, behavioral accuracy, and trial-to-trial subjective accuracy
      judgments were obtained from participants performing an antisaccade task, which
      elicits many unperceived, incorrect reflex-like saccades. Consistent with
      previous research, subjectively unperceived saccade errors were almost always
      immediately corrected, and were associated with faster correction times and
      smaller saccade sizes than perceived errors. Importantly, irrespective of whether
      the participant was aware of the error or not, erroneous saccades were followed
      by a sizable Ne. In contrast, the Pe was much more pronounced for perceived than
      for unperceived errors. Unperceived errors were characterized by the absence of
      posterror slowing. These and other results are consistent with the view that the
      Ne and Pe reflect the activity of two separate error monitoring processes, of
      which only the later process, reflected by the Pe, is associated with conscious
      error recognition and remedial action.

PMID- 11577899
TI  - The misclassification of blinks as saccades: implications for investigations of
      eye movement dysfunction in schizophrenia.
AB  - It is important to have a simple. accurate method for recording eye movements. Of
      the two popular approaches commonly adopted, electro-oculography (EOG) and
      infrared oculography (IROG), IROG is often accepted as the more accurate, and it
      is the method that is currently used most frequently to examine eye movements in
      schizophrenia. This study investigated whether the misclassification of blinks as
      saccades affects saccade rates when the presence of a blink is determined using
      only IROG recordings of eye position. Both vertical electro-oculography (VEOG),
      which can be used to objectively identify blinks, and IROG were recorded while 17
      schizophrenia patients and 19 healthy controls were presented with sinusoidal
      stimuli. Of the blinks identified with the VEOG for the total group of
      participants, a substantial number (37%) were misclassified as catch-up and
      anticipatory saccades when only the IROG was used. Furthermore, in the
      schizophrenia group, but not in the healthy control group, the use of the IROG
      led to a significant misclassification of blinks as anticipatory saccades.
      Therefore, when IROG alone is used to identify blinks, the misclassification of
      blinks as saccades is likely to introduce measurement error into estimates of
      saccade rates, particularly estimates of anticipatory saccade rates in
      schizophrenia patients.

PMID- 11577900
TI  - Laser-evoked potentials to noxious stimulation during hypnotic analgesia and
      distraction of attention suggest different brain mechanisms of pain control.
AB  - Psychological accounts of hypnosis have hypothesized that hypnosis and attention
      might share similar mechanisms and that hypnosis simply represents an extensive
      state of reduced attention. This assumption implies that reports of pain and
      electrocortical brain responses to painful stimulation should be similarly
      reduced when subjects are exposed to suggestions of hypnotic analgesia (HA) or
      requested to distract their attention from painful stimuli (distraction of
      attention: DA) as compared to a control condition (CC). To test this hypothesis,
      we recorded event-related electrical brain potentials to noxious laser-heat
      stimuli and pain reports during HA, DA, and CC from subjects highly susceptible
      to hypnotic suggestions. Pain reports were significantly reduced during HA and DA
      as compared to CC. The amplitudes of the late laser-evoked brain potential (LEP)
      components N200 and P320 were also significantly smaller during DA than during
      CC. However, no significant difference of these late LEP amplitudes was obtained
      for HA as compared to CC. Results indicate that hypnotic analgesia and
      distraction of attention represent different mechanisms of pain control and
      involve different brain mechanisms.

PMID- 11577901
TI  - The lateralized readiness potential and response kinetics in response-time tasks.
AB  - Previous studies have found that the magnitude of the lateralized readiness
      potential (LRP) at the time of response initiation is constant across spontaneous
      variations in response time in both cued and uncued, speeded tasks. Other studies
      have found that the LRP is also unaffected by instructed changes in peak response
      force and time to peak force in cued, self-paced tasks, but that the LRP is
      sensitive to instructed changes in force gain rate in uncued, self-paced tasks.
      The present study examined the LRP in an uncued, speeded task as a function of
      response time and several measures of response kinetics. The magnitude of the LRP
      at the time of electromyographic onset was constant across spontaneous variations
      in all measures. The peak of the contingent negative variation did vary as a
      function of peak response force and integrated force to peak, but not response
      time. These findings support the idea that the LRP in speeded tasks is a
      selective, on-line index of the preparation associated with using a particular
      hand, and is not an index of the elements of motor programming that determine
      subsequent response kinetics.

PMID- 11577902
TI  - Is pre-attentive processing compromised by prolonged wakefulness? Effects of
      total sleep deprivation on the mismatch negativity.
AB  - We investigated the potential influence of sustained wakefulness on pre-attentive
      capacities by recording the mismatch negativity (MMN), an electrophysiological
      manifestation associated with nonintentional detection of auditory oddball
      stimuli. The MMN was elicited by pitch deviants presented to both ears via
      earphones, at the beginning of a total sleep deprivation session (baseline),
      after 24 hr, and after 36 hr of continuous controlled wakefulness. A conspicuous
      MMN response was elicited at all three sessions. With time, however, a small yet
      significant gradual reduction in the MMN amplitude was evident. Whereas previous
      research suggested that controlled attention-demanding tasks are hampered by
      sleep deprivation, the balance of the present results suggests that passive
      (total) sleep deprivation may also bring about some degradation in the pre
      attentive detection of environmental irregularities and as a consequence may
      disrupt the reflexive shift of attention induced by such events.

PMID- 11577903
TI  - G theory and the reliability of psychophysiological measures: a tutorial.
AB  - For some years, the limits of classic reliability theory have been recognized in
      favor of the Generalizability Theory, which deals simultaneously with multiple
      sources of error. This measurement model can be particularly useful when applied
      to research in cognitive psychophysiology. Indeed, studies in this field often
      deal with estimated measures whose reliability is rarely taken into account. In
      this paper, we report two generalizability studies in order to investigate the
      usefulness of G theory in providing information about the reliability of
      experimental results. The first was carried out on P300 measured during an
      oddball task, and the second was carried out on ERPs recorded during a
      recognition memory task. As expected, results showed that P300 modulation was
      more reliable than ERP memory modulation. This suggests that G theory can be a
      useful tool to estimate the reliability of psychophysiological findings,
      complementing and extending results from conventional analyses.

PMID- 11577904
TI  - Conditioned inhibition of fear-potentiated startle and skin conductance in
      humans.
AB  - Conditioned inhibition of classical conditioning was investigated with the
      startle reflex and the skin conductance response (SCR) in humans using a serial
      presentation of the conditioned inhibitor (X) and of the conditioned stimulus
      (CS). The unconditioned stimulus (US) was a shock. During conditioning,
      participants were presented with two different reinforced CS (A, B) and with X
      preceding A (noted X-->A). During X-->A, A was not reinforced with the US. During
      the summation test, B, X-->B, and Y-->B were presented (Y was a new stimulus that
      tested the specificity of the inhibitory properties of X). B was not reinforced
      during the summation test. A, B, X, and Y were lights of different colors.
      Participants were divided into a low and a high anxious group based on the TPQ
      (C.R. Cloninger, 1987). In the low anxious group, conditioned startle
      potentiation and SCR responses to A were inhibited when X preceded A (noted
      A(XA)). This differential responding to A and A(XA) emerged earlier with the SCR
      than with startle. During the summation test, the inhibitory properties of X did
      not transfer to B. In the high anxious group, there was only a differential SCR
      to A and A(XA). X did not inhibit startle potentiation to A.

PMID- 11577905
TI  - Using the jackknife-based scoring method for measuring LRP onset effects in
      factorial designs.
AB  - Miller, Patterson, and Ulrich (1998) introduced a jackknife-based method for
      measuring the differences between two conditions in the onset latencies of the
      lateralized readiness potential (LRP). The present paper generalizes such
      jackknife-based methods to factorial experiments with any combination of within-
      and between subjects factors. Specifically, we introduce a subsample scoring
      method to assess potential main and interaction effects on LRP onsets within
      conventional yet slightly adjusted analyses of variance (ANOVAs) and post hoc
      comparison procedures.

PMID- 11577906
TI  - Time-of-day variations in different measures of sleepiness (MSLT, pupillography,
      and SSS) and their interrelations.
AB  - The aim of the present study is to analyze how well physiological measures of
      sleepiness derived from pupillography and the Multiple Sleep Latency Test
      correlate with a subjective measure, the Stanford Sleepiness Scale (SSS) score.
      The results are based on data from 12 healthy participants, who underwent these
      tests every 2 hr from 7:00 a.m. until 11:00 p.m. Sleep latencies were correlated
      with four different variables derived from pupillography and the SSS score. The
      results indicate that the physiologically based variables correspond very well.
      This is reflected by similar patterns of time-of-day variations, a good agreement
      at the group level, and correlations at the individual level, whereas the SSS
      shows a quite different pattern of variation. The two physiological measures of
      sleepiness seem to reflect the same aspect of the level of tonic central nervous
      activation, which is not correlated with the subjective feeling of sleepiness.

PMID- 11577907
TI  - Differential effects of active versus passive coping on secretory immunity.
AB  - This study examined the acute immunological effects of two laboratory stressors,
      expected to evoke distinct patterns of cardiac autonomic activity; namely an
      "active coping" time-paced memory test, and a "passive coping" stressful video
      showing surgical operations. We measured salivary S-IgA, IgA-subclasses (IgA1,
      IgA2), and secretory component (SC). SC is responsible for the transport of S-IgA
      across the epithelium, and thus a rate-determining step in S-IgA secretion.
      Thirty-two male undergraduates were subjected to both stressors and a control
      video (a didactic television program). The memory test induced a typical "fight
      flight" response, characterized by increases in heart rate and blood pressure in
      association with a decrease in cardiac preejection period (PEP) and vagal tone.
      The surgical video produced a "conservation-withdrawal"-like response,
      characterized by an enhanced vagal tone, a decrease in heart rate, and a moderate
      sympathetic coactivation (as indicated by a shortened PEP and an increased
      systolic pressure). The memory test induced an increase in the concentration and,
      to a lesser extent, in the output of S-IgA, IgA], and SC. The output of IgA2 was
      not significantly affected. For the surgical video, a different pattern emerged:
      During stressor exposure S-IgA remained unaffected, against the background of a
      small increase in SC output. However, 10 min after the surgical video S-IgA
      levels had decreased. This decrease in S-IgA was paralleled by a decrease in
      IgA1, but not IgA2. We conclude that acute stress can have both enhancing and
      suppressive effects on secretory immunity, the IgA1 subclass in particular. The
      mechanisms that underlie these divergent responses may include stressor-specific
      patterns of autonomic activation.

PMID- 11577908
TI  - The quest for the EEG reference revisited: a glance from brain asymmetry
      research.
AB  - Recent findings suggested that the choice of the EEG reference might be a
      critical issue for the study of anterior asymmetry in the alpha band. The present
      paper investigates the validity of different reference schemes for the
      measurement of alpha asymmetry. A 32-channel resting EEG was recorded with a
      common vertex reference (Cz), and transformed into computer-averaged ears (A1 +
      A2), average reference (AR), and current source density derivations. A
      correlation analysis of an alpha asymmetry measure between all derivation schemes
      indicated a poor convergent validity for anterior sites but an excellent
      convergent validity for posterior sites. Further analyses suggested the presence
      of substantial alpha activity at the various reference sites (Cz, A1 + A2, AR),
      which might be similar in magnitude to anterior but smaller than posterior alpha.
      These findings suggest that the validity of a reference scheme is a function of
      the signal-to-noise ratio of the electrical activities at target and reference
      sites. The limitations of each reference scheme for the measurement of anterior
      alpha asymmetry are discussed.

PMID- 11577909
TI  - Modulation of respiratory sinus arrhythmia by respiration rate and volume:
      stability across posture and volume variations.
AB  - We tested the assumption that the slope of the within-individual regression
      equation of respiratory sinus arrhythmia (RSA) normalized by tidal volume (V(T))
      upon respiratory cycle length (T(TOT)) can characterize ventilatory RSA
      modulation independent of cardiac vagal tone, whereas the intercept is varying as
      a function of vagal tone. We also explored whether a variation of V(T) is
      necessary to estimate slopes reliably. Four 3-min sequences paced at 8-18
      cycles/min were performed supine and standing. Participants also breathed the
      same sequences in supine posture with voluntarily varying V(T). The mean slope of
      RSA/V(T) upon T(TOT) was identical, and the mean intercept was lower for standing
      than supine (spontaneous V(T)) conditions. Stability of slopes was low between
      body postures, and was higher between spontaneous V(T) versus varying V(T) at the
      same body posture. The regression of RSA/V(T) upon T(TOT) allows for a valid
      estimation of ventilatory influences on RSA.

PMID- 11577910
TI  - Body attitudes and body experiences in suicidal adolescents.
AB  - The relationships between cognitive and affective attitudes toward the body, body
      experiences (dissociation, insensitivity, and lack of control), and suicidal
      tendencies were examined as a derivative of the hypothesis that bodily attitudes
      and experiences may facilitate suicidal acting out. Three groups of adolescents
      (aged 14-18), including suicidal (made a suicide attempt) and nonsuicidal
      inpatients and controls, were compared with regard to suicidal tendencies,
      various body aspects, and depression and anxiety. A series of MANOVAs,
      discriminant analysis, Pearson correlations, and regressions were employed. The
      results show that the suicidal group differed from the two nonsuicidal groups in
      feelings toward the body, body protection, and body dissociation. Some aspects of
      bodily measures discriminated between suicidal and nonsuicidal subjects. In
      addition, various bodily measures were associated with and statistically
      predicted suicidal tendencies. The discussion focuses on the web of associations
      between body attitudes and experiences and their role in suicidal behavior.

PMID- 11577911
TI  - Suicidality patterns and sexual orientation-related factors among lesbian, gay,
      and bisexual youths.
AB  - Three hundred fifty lesbian, gay, and bisexual youths aged 14 to 21 years were
      questioned about suicidal thoughts and behaviors, families' reactions to youths'
      sexual orientation, and suicidality among relatives and friends. Results
      confirmed an association between sexual orientation and suicidality. Nearly half
      (42%) had sometimes or often thought of suicide; one third (33%) reported at
      least one suicide attempt. Many related suicidal ideation and suicide attempts to
      their sexual orientation. Most attempts followed awareness of same-sex feelings
      and preceded disclosure of sexual orientation to others. One quarter said a
      family member had made a suicide attempt, and nearly three quarters said a close
      friend had attempted suicide.

PMID- 11577912
TI  - Activity involvement among suicidal and nonsuicidal high-risk and typical
      adolescents.
AB  - The purpose of this study was to compare weekly activities among four groups of
      randomly selected high-risk and typical high school students: (1) potential
      dropouts at suicide risk, (2) typical youth at suicide risk, (3) potential
      dropouts not at suicide risk, and (4) typical youth not at suicide risk. Of the
      1,286 participants, 39.4% of the high-risk and 30.1% of typical high school
      students screened in at suicide risk. Weekly activity comparisons across the four
      groups showed that suicide-risk adolescents, regardless of potential dropout
      status, engaged in more solitary activities on weekdays and weekends than did
      their nonsuicide risk peers. High-risk potential dropout youth engaged in less
      homework and more social activities during weekdays and weekends than did the
      typical high school students. These results provide important insight into the
      weekly activity involvement of at-risk youth while helping to gain a better
      understanding of suicide-risk adolescents. Implications of these findings are
      discussed for identifying youth at risk for suicidal behavior and for prevention
      programming.

PMID- 11577913
TI  - An investigation of psychopathology in nonreferred suicidal and nonsuicidal
      adolescents.
AB  - This investigation examined self-reported psychopathology in a school-based
      sample of 456 suicidal and nonsuicidal adolescents. The sample consisted of four
      groups: three at-risk for suicidal behavior based on current suicidal ideation as
      assessed by the Suicidal Ideation Questionnaire (SIQ; Reynolds, 1988), past
      suicide attempts, or both; and one nonsuicidal comparison group. Psychopathology
      was examined using ten scales from the Adolescent Psychopathology Scale (APS;
      Reynolds, 1998a) including: Major Depression, Conduct Disorder, Substance Abuse,
      Schizophrenia, Adjustment Disorder, Anorexia Nervosa, Borderline Personality
      Disorder, Obsessive-Compulsive Personality Disorder, Schizotypal Personality
      Disorder, and Avoidant Personality Disorder. Analyses were conducted separately
      for males and females using a MANOVA design that examined psychopathology
      severity among the four groups. Adolescents who engaged in past or current
      suicidal behavior had higher psychopathology severity scores compared to their
      nonsuicidal peers. Males with current suicidal thoughts who had attempted suicide
      had the highest levels of psychopathology severity compared to males in the other
      three groups. Females with a past suicide attempt or current suicidal ideation
      had higher psychopathology severity scores compared to nonsuicidal females.
      Results show greater psychopathology in school-based adolescents who have engaged
      in past and/or current suicidal behavior. The need for clinicians and mental
      health professionals working with at-risk youth to focus on concurrent
      psychopathology along with suicidal behavior is discussed.

PMID- 11577914
TI  - Suicide and firearm prevalence: are youth disproportionately affected?
AB  - The effect of firearm availability on suicide may differ among age groups. We
      used regression analysis to examine the relationship between suicide rates and
      household firearm ownership for four age groups in the nine census regions from
      1979 to 1994, adjusting for regional divorce rates, education, unemployment, and
      urbanicity. Results showed that firearm ownership levels are correlated with
      suicide rates among 15- to 24-year-olds and 65- to 84-year-olds, but not among 25
      to 64-year-olds. The findings suggest that if the relationship is causal, a 10%
      fall in regional firearm ownership levels would lead to a 3.0% decrease in
      suicide rates.

PMID- 11577916
TI  - Educating parents about youth suicide: knowledge, response to suicidal
      statements, attitudes, and intention to help.
AB  - This study evaluated the video Youth Suicide: Recognising the Signs as a parent
      educational medium. Before and after viewing the video, parents (N = 112) of
      young people answered questionnaires measuring their (1) knowledge of suicidal
      signs, (2) responses to a young person showing suicidal signs, (3) attitude to
      suicide, and (4) intentionalitv toward suicidal people. After the video, parents'
      knowledge of suicidal signs, responses toward a suicidal person, and intention to
      help improved. Their attitude was more rejecting of suicide. Knowledge and
      intentionality predicted response to suicidal statements, but no relationships
      existed between attitude and the other variables. Implications for youth suicide
      education programs are discussed.

PMID- 11577915
TI  - Stressful life events and impulsiveness in failed suicide.
AB  - The relationship of recent stressful life events with impulsiveness in triggering
      suicide attempts and how impulsiveness changes from one suicide attempt to
      another is unclear. This study used structured-interview tools and standardized
      measurements to examine the relationship between life stress and impulsiveness in
      a sample of patients who required hospitalization for a medically serious suicide
      attempt. After controlling for potentially confounding variables, the number of
      disrupted interpersonal relationships in the preceding year was a significant
      predictor of the impulsiveness of the suicide attempt, with three or more losses
      (but not other life stresses) associated with less impulsive attempts (T = 2.4, p
      = .02). Female gender (T = -1.98, p = .05) and lifetime DMS-III-R diagnoses (T = 
      2.45, p = .02) were significantly associated with more impulsive attempts. In 55
      patients with at least two suicide attempts, impulsiveness, lethal intent, and
      communication of intent were significantly greater for the present compared to
      the prior attempt (p = 0.000). Certain stressful life events, gender, and total
      lifetime DSM-III-R diagnoses are associated with impulsiveness of failed suicide
      attempts; yet, impulsiveness is not necessarily consistent from one suicide
      attempt to another. This evidence supports and amplifies a stress-diathesis model
      of suicide behavior. Accordingly, efforts to increase personal resilience in
      individuals who have "failed suicide" may be more effective at preventing suicide
      morbidity than simple stress-reduction measures alone.

PMID- 11577917
TI  - Attitudes toward the unification of Western Europe and cross-national suicide
      rates: eight European countries, 1973-1990.
AB  - Durkheim's (1897/1951) theory of political integration argues that when political
      crises occur, individuals band together to solve the problem at hand. As a
      result, this increased integration yields lower suicide rates. The purpose of
      this analysis is to examine a different component of the concept of political
      integration-that of attitudes. During the past couple of decades, individuals in
      eight Western European countries have been asked about their attitudes toward the
      unification of Western Europe. Cross-sectional time series analysis reveals that
      the attitudes individuals hold toward such an event are significantly related to
      suicide rates. Although Durkheim's theory of political integration focuses on
      events within a given country, the research herein finds that political
      integration exists on an international level as well. A reformulation of
      Durkheim's theory of political integration is put forth.

PMID- 11577918
TI  - Attitudes toward suicide prevention in front-line health staff.
AB  - A questionnaire assessing attitudes toward suicide prevention was constructed and
      shown to have satisfactory reliability and internal consistency. The determinants
      and distribution of these attitudes were investigated in four groups of health
      professionals who are in contact with suicidal patients: general practitioners,
      accident and emergency nurses, psychiatrists in training, and community
      psychiatric nurses. Attitudes toward suicide prevention were shown to differ
      significantly between professional groups. More positive attitudes were
      associated with mental health professionals, working in the community, and
      previous training in suicide risk assessment. Negative attitudes should be
      assessed and targeted in training designed to improve the management of suicide
      risk.

PMID- 11577919
TI  - U.S. involuntary mental health commitment statutes: requirements for persons
      perceived to be a potential harm to self.
AB  - The civil commitment statutes of all 50 states and the District of Columbia were
      reviewed to determine: (1) What is required for a person who is believed to be at
      serious and imminent risk of self-harm to be eligible for involuntary
      hospitalization; and (2) Whether an attempt to involuntarily hospitalize was
      required or was merely an option when the requirements found in number 1 were
      met. The analysis revealed that nearly 85% of the jurisdictions require
      dangerousness to self to be the result of a mental illness, and only two
      jurisdictions mandate attempts at involuntary commitment if a person is deemed to
      be an imminent harm to self. These results have implications for practice with
      individuals who are suicidal.

PMID- 11577920
TI  - Early suicide following discharge from a psychiatric hospital.
AB  - Social and clinical risk factors for completed suicide occurring shortly after
      discharge from a psychiatric hospital were examined in this case-control study.
      Seventy-seven individuals who received "suicide" or "undetermined death" verdicts
      at inquest, and who had been previously discharged from psychiatric hospitals in
      Bradford, U.K., were compared with a control group. A history of deliberate self
      harm was significantly associated with early suicides compared with both late
      suicides and controls. A diagnosis of mood disorder, specifically depression, and
      longer case-notes were also significantly associated with early suicides compared
      to controls. This study has implications for risk management of recently
      discharged psychiatric patients.

PMID- 11577921
TI  - Efficacy and tolerability of cisapride in children.
AB  - As gastro-oesophageal reflux disease (GORD) in infants and children is a motility
      disorder which differs in pathophysiology and clinical course from GORD in
      adults, prokinetics should be considered the drug of choice in certain
      circumstances. Indeed, cisapride may result in improvement of feeding tolerance
      in premature infants. Cisapride has a better tolerability profile than a 'wait
      and-see-if-improvement-comes-spontaneously' policy or the other therapeutic
      options available. A careful and critical review of published data suggests that
      cisapride may have a QTc-prolonging effect. However, provided the precautions for
      cisapride administration are followed, the QTc-prolonging effect remains
      consistently without clinically relevant adverse effects. Correct dosage and
      avoidance of concurrent treatment with macrolides and/or azoles are the most
      relevant tolerability recommendations in children. Although there is a need for a
      prokinetic with better efficacy, cisapride is currently the prokinetic with the
      best benefit-to-risk ratio available. Thus, withdrawal of cisapride would result
      in a significantly increased risk for severe complications in infants and
      children with GORD or other gastrointestinal motility disorders such as chronic
      intestinal pseudo-obstruction, gastroparesis and feed intolerance in premature
      infants.

PMID- 11577922
TI  - Recognition and management of scleroderma in children.
AB  - Juvenile scleroderma is a rare disease of childhood. The 2 main forms are
      localised and systemic scleroderma, although the pathogenesis of both forms is
      still unclear. The main clinical characteristic is the presence of skin
      sclerosis. Localised scleroderma can be divided into 3 different subtypes:
      morphoea, linear scleroderma and 'coup de sabre' lesions. The incidence is 0.2 to
      0.4 per 100,000. 25 to 40% of patients are rheumatoid factor positive and 23 to
      67% antinuclear antibody positive. An increased number of eosinophils occur in
      31% of patients. Systemic sclerosis is an even rarer disease; approximately 10%
      of patients evolve the disease before the age of 18 years. The clinical
      presentation and disease course differ from the adult disease. This is reflected
      in the much better outcome. With regard to therapeutic options, there is still no
      gold standard for either form of the disease.

PMID- 11577923
TI  - Prevention and management of febrile seizures.
AB  - Febrile seizures are the most common seizures in childhood and, like all
      seizures, can be frightening to witness. Therefore, it is not surprising that
      febrile seizures have been the focus of intense research with an extensive
      literature describing various preventative measures. In addition, there is also
      an extensive and sophisticated epidemiological literature delineating the natural
      history of this disorder in American and British children. For simple febrile
      seizures, the most common form of this disorder, the epidemiological studies
      demonstrate a generally benign natural history, making it unlikely that any
      preventative measure could improve the long term outcome for most children.
      Children with simple febrile seizures have a slight increased risk of epilepsy,
      but there are no studies that demonstrate that phenobarbital or other therapy can
      alter this risk. Daily therapy with phenobarbital or valproic acid can reduce the
      number of subsequent simple febrile seizures. However, as a recent Practice
      Parameter from the American Academy of Paediatrics concludes, the risk of adverse
      effects from daily therapy appears to outweigh the benefit of preventing the
      short term recurrence of simple febrile seizures. It is possible that in some
      families, where the occurrence of an additional simple febrile seizure would be
      particularly distressing, the routine use of oral diazepam during febrile
      illnesses might be appropriate.

PMID- 11577924
TI  - Clinical aspects and antiviral therapy in primary herpetic gingivostomatitis.
AB  - Primary symptomatic herpes simplex virus infection in children usually manifests
      as gingivostomatitis and is prevalent in the 1- to 3-year age group. The disease
      involves the buccal and gingival mucosa and the tongue, and lasts approximately 2
      weeks. Two recent non-blind studies reported a more rapid regression of symptoms
      after treatment with aciclovir suspension. Three randomised double-blind, placebo
      controlled trials have clearly demonstrated that early aciclovir treatment
      significantly shortens the duration of all clinical manifestations and
      infectivity of affected children compared with placebo. We conclude that the
      treatment of herpetic gingivostomatitis with aciclovir is recommended. Treatment
      should be started within the first 3 days of disease onset. The proposed
      therapeutic dose is 15 mg/kg, 5 times daily for 5 to 7 days.

PMID- 11577925
TI  - Congenital adrenal hyperplasia: epidemiology, management and practical drug
      treatment.
AB  - Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency is a
      common disorder, and is characterised by a defect in cortisol biosynthesis with
      or without a defect in aldosterone synthesis and androgen excess. The classic
      form, also known as the severe form, occurs in 1:15,000 births worldwide, while
      the nonclassic or mild form occurs in approximately 1:1,000 births worldwide and
      is much more common (up to 1:20) in certain ethnic groups. In classic 21
      hydroxylase deficiency, glucocorticoids are given in doses sufficient to suppress
      adrenal androgen secretion, and mineralocorticoids are given to normalise
      electrolytes and plasma renin activity. The management of CAH may be complicated
      by iatrogenic Cushing's syndrome, inadequately treated hyperandrogenism, or both.
      Prenatal treatment may decrease virilisation of the affected female foetus, but
      the efficacy and safety of treating CAH prenatally remains to be fully defined.
      Close clinical monitoring of growth and development is essential to optimise
      treatment outcome. New treatment approaches are currently under investigation in
      the most severely affected patients, while nonclassic CAH does not always require
      treatment.

PMID- 11577927
TI  - Lessons from medical toxicology.

PMID- 11577926
TI  - Sudden death related to selected tricyclic antidepressants in children:
      epidemiology, mechanisms and clinical implications.
AB  - The association between tricyclic antidepressant (TCA) use in children and
      increased risk of sudden death is unclear, but still possible. There are suitable
      alternatives to TCAs for all of the indications in which they have shown
      efficacy. A prudent practice model for the utilisation of TCAs has been
      developed. This includes initial utilisation of alternative agents, with TCAs as
      secondary or tertiary choices; informed consent from patient and family,
      including mention of the possible relationship of TCA with sudden death;
      vigilance of the emerging literature; and finally, systematic monitoring of
      patients, including electrocardiograms, drug serum concentrations and vital
      signs. This protocol needs to be validated with regard to utility and the degree
      of assistance it provides in the management of children treated with TCAs.

PMID- 11577928
TI  - Efficacy of hexafluorine for emergent decontamination of hydrofluoric acid eye
      and skin splashes.
AB  - Hexafluorine is an amphoteric, hypertonic, polyvalent compound for
      decontaminating hydrofluoric acid (HF) eye and skin splashes. In a German
      metallurgy facility during the period of 1994-1998, all eye or skin splashes with
      40% HF alone or with a 6% HF/15% HNO3 mixture were initially decontaminated with
      Hexafluorine within 2 min following the splash at the accident site by the
      victims themselves or co-workers who witnessed the accident. Eleven workers using
      40% HF or a 6% HF/15% HNO3 mixture sustained eye (2 cases) or skin (10 cases)
      splashes (1 combined) during 1994-1998. Hexafluorine was used within 2 min, and a
      second Hexafluorine decontamination was done on arrival at the plant infirmary.
      No further medical or surgical treatment was needed, no workers developed
      chemical burns, and none lost work time. These II cases demonstrate the efficacy
      of Hexafluorine in decontaminating HF or combined HF/HNO3 splashes.

PMID- 11577929
TI  - Inhibition of glycosidases by Astragalus lusitanicus and correlation with
      toxicity.
AB  - This study determined whether Astragalus lusitanicus inhibits glycosidase enzymes
      other than alpha-mannosidase. Plasma collected from lambs given fresh A
      lusitanicus inhibited beta-glucosidase and beta-galactosidase, indicating the
      presence of inhibitors in their blood. The residual activity of these enzymes was
      also modified in tissues of dead animals. beta-glucosidase activity was reduced
      in liver and kidney specimens with pronounced effects in tissues of animal that
      presented with prominent clinical signs of poisoning; beta-galactosidase activity
      was decreased by 88.5 to 95% in kidney, while that of liver remained unchanged.
      Fractions of the plant butanol extract inhibited the gycosidase enzymes. Chemical
      analysis revealed the presence of hypaphorin in the extract of A lusitanicus. As
      a tryptophan derivative, this alkaloid may play a role in the toxicity of this
      legume.

PMID- 11577930
TI  - Subchronic peroral toxicity of triethylene glycol in the Fischer 344 rat.
AB  - Ethylene and diethylene glycols produce systemic toxicity, including
      nephrotoxicity, by acute and repeated po dosing. To determine the potential for
      triethylene glycol (TEG; CAS Number 112-27-61) to produce nephrotoxicity, or
      other organ/tissue injury, a subchronic (90-d) study was conducted by continuous
      inclusion of TEG in the diet of Fischer 344 rats. This was preceded by a probe 14
      d study. For both studies the dietary concentrations were 0 ppm (control),
      10,000, 20,000 or 50,000 ppm TEG, resulting in daily TEG consumptions in the 14-d
      study of 1132, 2311 or 5916 mg/kg with males, and 1177, 2411 or 6209 mg/kg with
      females. The corresponding values for the 90-d study were 748, 1522 or 3849 mg/kg
      (males), and 848, 1699 or 4360 mg/kg (females). In the 14-d study there were no
      mortalities or clinical signs, and no effects on body weight, hematology, serum
      chemistry, organ weights, and gross or microscopic pathology. Food consumption
      was increased at the high dosage. Urinalysis showed increased urine volume and
      decreased pH with high dose males and females, and increased volume with mid-dose
      males. In the subchronic study there was neither mortality nor signs of toxicity,
      and no dosage-related effects with serum chemistry, gross and microscopic
      pathology. Body weights were reduced during the dosing period with both males and
      females of the high dosage. Body weight gains were reduced at all dosages with
      males and females. No hematological effects were seen with females, but males of
      the mid- and high-dosage groups had slightly reduced erythrocyte count and
      hematocrit, and high-dose males had decreased hemoglobin concentration with
      increased mean corpuscular volume. These were considered to reflect a mild
      hemodilution related to the absorption of large TEG doses. Urinalysis showed
      dosage-related decreased pH, and increased urine volume mainly at the high dose.
      These were probably related to the renal excretion of absorbed TEG and/or
      metabolites. Kidney weight was increased for high-dose females, and increased
      relative (to body) weight of kidneys for males and females from the mid- and high
      dose groups were observed, probably related to the renal excretion of the
      absorbed TEG and/or its metabolites. These findings indicate that the subchronic
      continuous po dosing of TEG to rats does not result in local or systemic specific
      organ or tissue toxicity. These findings contrast with the known repeated po
      toxicity, notably nephrotoxicity, produced by ethylene and diethylene glycols.
      Thus, TEG has significantly lesser potential for systemic toxicity by the po
      route than its lower molecular weight homologues.

PMID- 11577931
TI  - Acute mercuric chloride poisoning: effect of co-ingested milk on outcome and
      continued hyperamylasemia.
AB  - Thirty-six h after intentionally ingesting 25 g of mercuric chloride powder mixed
      with 5O mL of milk, an elderly woman presented to the emergency department with
      diffuse upper gastrointestinal erosions and acute renal failure. The patient was
      treated with dimercaprol and hemodialysis, and was discharged from the hospital
      without clinically apparent sequelae. However, elevated serum concentrations of
      amylase and proteases persisted for several months despite normal findings by
      computed tomography including contrast administration. Delayed absorption and
      weakened corrosive effect may have resulted from the binding of mercuric chloride
      to thiol-containing proteins in milk, improving the clinical outcome.

PMID- 11577932
TI  - Beef cattle losses after grazing Lupinus argenteus (silvery lupine).
AB  - Ten yearling steers weighing 270-360 kg died acutely after eating early seed pod
      stage Lupinus argenteus (silvery lupine) containing high levels of piperidine
      alkaloids, including ammodendrine and N-methylammodendrine. Reduced availability
      of Quality feed from range moderately depleted of Quality grasses appeared a
      major factor in causing the cattle to graze lupine. Proximate analysis of whole
      plant, seed pods and seed showed high levels of crude protein ranging from 16.4
      to 48% for whole plant and seed. Alkaloid analysis of the whole plant and
      individual plant parts such as seed and seed pods (30-40% seed shatter) showed
      total alkaloid levels ranging from 0.70 to 2.5% (0.70-2.5 mg/100 mg plant) dry
      weight. Ammodendrine levels ranged from 0.24% in seed pods with >70% seed loss to
      1.35% in early growth plant with no seed. N-methylammodendrine levels ranged from
      0.38% in seed pods with >70 % seed shatter to 1.04 % in pure seed. Other minor
      alkaloids totaled 0.08% in seed pods with >70% seed shatter to 0.60% in early
      growth plant before seed pod formation. These cattle ate an estimated 1.8 g/kg
      dry weight (486 g to 648 g) of lupine in 24 h. This appears the first report of
      acute death in cattle associated with piperidine alkaloid-containing Lupinus
      argenteus.

PMID- 11577933
TI  - Snakebite complicated with Vibrio vulnificus infection.
AB  - Snakebite may be complicated with bacteria infections, most of which are Gram
      negative bacillus. Snakebite complicated with Vibrio vulnificus infection has not
      been reported previously. Vibrio vulnificus infection is characterized by a
      necrotizing wound infection similar to the local lesion of severe snakebite. In
      Vibrio infections, aggressive debridement with the administration of strong
      antibiotics as early as possible is the only effective treatment. We report a 79
      y-o man who suffered from snakebite on the right palm with rapid progression of
      hemorrhagic bulla, necrotizing fasciitis, compartment syndrome, and septic shock.
      Vibrio vulnificuswas cultured from necrotic tissue after aggressive debridement
      and fasciotomy. The patient recovered from antibiotic treatment and several
      courses of reconstruction surgery. Severe bacteria infection, such as caused by
      Vibrio vulnificus, should be considered in snakebite cases refractory to
      antivenin dosage.

PMID- 11577934
TI  - Aminophylline reversal of antihypertensive agent toxicity.
AB  - Hypotension occurred following a combined beta blocker (atenolol), angiotensin
      converting enzyme inhibitor (quinapil) and selective serotonin reuptake inhibitor
      (fluvoxamine) overdose. In another instance heart block and hypotension was noted
      in association with a diltiazem and atenolol adverse interaction. Crystalloid
      infusion was ineffective in both cases, but toxicity was rapidly reversed with
      aminophylline administration. Aminophylline's recognized inotropic and
      chronotropic properties make it a potentially valuable therapeutic agent in the
      treatment of antihypertensive medication toxicity.

PMID- 11577935
TI  - Bite the bullet: lead poisoning after ingestion of 206 lead bullets.
AB  - A 45-y-o male with a history of schizophrenia was admitted to a local VA
      psychiatric unit. Five days later, endoscopy due to abdominal pain,
      gastrointestinal bleeding and blood hemoglobin of 5.6 g/dL revealed bullets in
      the stomach. On subsequent radiograph, > 50 bullets were visualized in the
      stomach and intestines. Poison Center recommendations included whole bowel
      irrigation and a blood lead level. After poor results with gastrointestinal
      decontamination and a repeat radiograph showing > 100 cartridges, surgical
      intervention was considered but not performed due to perceived risk of bullet
      detonation from electrocautery. The blood lead was reported as 391 mcg/dL.
      Calcium EDTA therapy was initiated, followed by aggressive gastrointestinal
      decontamination. Four days of whole bowel irrigation facilitated passage of 206
      cartridges over the next 10 days. The patient was discharged on a 14-day course
      of 600 mg Succimer tid to treat the bone lead deposits and blood lead level of 49
      mcg/dl. An outpatient visit 6 w later showed the blood lead level had dropped to
      24 mcg/dl. Aggressive gastrointestinal decontamination and calcium EDTA and
      Succimer administration successfully treated an ingestion lead bullets and the
      resulting lead poisoning.

PMID- 11577936
TI  - Lead content of fresh milk samples from different sites in Athens.
AB  - Milk and dairy products constitute a major food, especially for infants and
      children, and relatively low levels of toxic elements can contribute
      significantly to dietary intakes and be hazardous for public health. The purpose
      of this survey was to define the levels of lead in milk samples of different
      origin, to establish the presence or absence of contamination. The milks from
      different sites of the metropolitan area of Athens contained negligible traces of
      lead and thus are safe for the public health.

PMID- 11577937
TI  - Determination of aflatoxin M1 levels in cheese and milk consumed in Bursa,
      Turkey.
AB  - Aflatoxin M1 (AFM1) was determined by ELISA in 57 cheese and 10 milk samples
      collected from supermarkets and street milkmen during August in Bursa Province,
      Turkey. The highest AFM1 concentration was 810.00 ng/kg in full fatty white
      cheese. The incidence of AFM1 in the cheese was higher (89.47%) than that of milk
      (10%). The AFM1 in 7/57 (12.28%) cheese samples exceeded the Turkish AFM1
      tolerance limits of 250 ng/kg, but none of the milk samples exceeded the FAO/WHO,
      European Union and Turkish tolerance limit of 50 ng/L.

PMID- 11577938
TI  - The toxicology of microcystin-LR: occurrence, toxicokinetics, toxicodynamics,
      diagnosis and treatment.
AB  - Cyanobacterial blooms occur worldwide and present an increasing problem due to
      eutrophication of lakes. Microcystins, especially microcystin-LR, are microcyclic
      heptapeptide hepatotoxins and are the most common and potent toxins associated
      with cyanobacteria. Microcystin is rapidly taken up by hepatocytes through
      carrier-mediated transport. Once in the hepatocyte, microcystin causes structural
      damage to the cell indirectly by inhibiting protein phosphorylases 1 and 2A,
      which are needed for regulation of structural proteins of the cell. Acute liver
      hemorrhage and death occur with high doses of microcystin-LR, which is also a
      potent tumor promoter in laboratory rats. The significance of microcystin to
      human health has been debated; however, poisoning in humans has occurred due to
      contaminated dialysis water. Microcystin in contaminated drinking water may be
      the cause of elevated rates of primary liver cancer in some areas of China.
      Problems with hepatotoxic cyanobacteria have been most seen in livestock.
      Treatment of confirmed microcystin toxicosis in livestock is likely to be
      unrewarding, so prevention is important. Wild mammals, birds, fish, insects, and
      microinvertebrates may also be affected by microcystin.

PMID- 11577939
TI  - Scientific basis and regulatory aspects for the toxicology of plant protection
      products in the European Union.
AB  - Authorization of plant protection products/agrochemicals/pesticides in the
      European Union is done on the basis of their toxicological properties. This paper
      reviews the current legislation for placing an agrochemical on the market (ie a
      new substance or a existing active substance), and the toxicology studies needed
      for inclusion of a substance in any of the annexes of the Council Directive of
      the European Economic Community 91/414/ EEC. Risk analysis and its steps is
      discussed. The "threshold toxicity" employed to allow risk characterisation of
      plant protection products is described, such as acceptable daily intake,
      acceptable operator exposure level, acute reference dose, and maximum admissible
      concentration in water.

PMID- 11577940
TI  - Neurologic disease in range goats associated with Oxytropis sericea (Locoweed)
      poisoning and water deprivation.
AB  - About 200/2500 Spanish goats foraging on mountain rangelands of western Montana
      developed neurologic disease with severe rear limb weakness, knuckling of the
      rear fetlocks, and a hopping gait. Sick goats were of all ages and in good flesh,
      though they often had dull, shaggy coats. Some mildly affected animals recovered
      after being moved to feed lots, but others progressed to recumbency, seizures and
      death. At necropsy both moribund and clinically affected animals had few gross
      lesions; 1 animal had contusions and puncture wounds on rear legs and perineum,
      suggestive of predator bites. Histologic lesions included mild vacuolation of
      neurons and visceral epithelial cells, mild diffuse cerebral edema with minimal
      neuronal pyknosis, and random, multifocal Wallarian degeneration of spinal cord
      axons. Affected animals had elevated serum sodium, potassium and chloride levels;
      other mineral analyses and serum biochemistries were within normal limits.
      Locoweed-induced depression and inhibition of neuromuscular function coupled with
      water deprivation due to predation pressure allowed development of neurologic
      disease and hypernatremia.

PMID- 11577941
TI  - A nationwide survey of poison control centers comparing 1999 to 1998 triage and
      management of asymptomatic children who ingested tricyclic antidepressant.
AB  - Triage of asymptomatic, unintentional pediatric (< 6y) tricyclic antidepressant
      (TCA) exposures has been based upon single cases or small studies involving large
      dose, symptomatic ingestions. This study evaluated patterns of triage for
      asymptomatic pediatric TCA exposures as practiced nationally by regional centers
      and compared them to 1998 patterns. It also evaluated the role of activated
      charcoal in the management of these exposures. Surveys were sent to the 30
      certified regional Poison Control Centers that responded to our 1998 survey.
      Twenty-two centers responded (73%). Fourteen (63%) referred to a health care
      facility based upon mg/kg, compared to 6 (20%) in 1998. Of the 14, 6 referred at
      doses >5 mg/kg compared to 2 (6.6%) in 1998. If referred to an emergency
      department, 18 (82%) recommended activated charcoal compared to 1 (3.3%) in 1998.
      The lowest toxic dose reported in the literature is 6.7 mg/kg. This is consistent
      with poison control data during the past 6y where no child became toxic at doses
      < 5 mg/kg. This survey demonstrated significant changes in triage patterns for
      asymptomatic pediatric TCA exposures.

PMID- 11577942
TI  - Southern African veterinary toxicology in the African context.

PMID- 11577943
TI  - A longitudinal clinical comparison of plaque-induced inflammation between
      gingival and peri-implant soft tissues in the maxilla.
AB  - BACKGROUND: Little information exists concerning the periimplant soft tissue
      response to plaque compared to the gingiva of the dentition. The purpose of this
      study was to compare this relative tissue response to plaque in humans over time.
      METHODS: Two hundred seventy-five (275) hydroxyapatite-coated implants were
      placed in the maxillae of 50 subjects followed by prosthetic rehabilitation.
      Baseline gingival (GI) and plaque (PI) index scores were obtained for all
      implants. Two to 4 teeth per subject were similarly measured, serving as
      controls. Measurements were repeated at 6-month intervals over 30-months. GI
      scores were evaluated relative to PI scores at 4 separate sites for each implant,
      to implant location within the oral cavity, and to length of time that each
      implant was in function. RESULTS: The peri-implant mucosa demonstrated a
      significantly greater likelihood of having elevated GI scores relative to PI
      scores when compared to the gingiva (chi-square for combined PI scores of 0 and 1
      = 85.0, df = 1, P <0.001; for combined P1 scores of 2 and 3 = 114.6, df = 1, P
      <0.001). A logistic generalized linear model confirmed the significance of these
      results (Student t for implant effect = 21.602). It further demonstrated
      significantly elevated GI scores for implant sites over time and for implants
      located in the posterior oral cavity. CONCLUSIONS: The results indicate that
      maxillary peri-implant soft tissues are at increased risk for plaque-induced
      inflammation relative to the gingiva of the dentition. Hygiene recall standards
      and treatment regimens may require revisions to minimize peri-implantitis and
      prevent bone loss.

PMID- 11577944
TI  - Fluids and microbial penetration in the internal part of cement-retained versus
      screw-retained implant-abutment connections.
AB  - BACKGROUND: It has been recently observed that in implants with screw-retained
      abutments, in in vitro as well as in vivo conditions, bacteria can penetrate
      inside the internal cavity of the implant as a consequence of leakage at the
      implant-abutment interface. An alternative to screw-retained abutments is
      represented by implants that can receive cemented abutments. In this case, the
      abutment goes through a transmucosal friction implant extension (collar) and is
      cemented inside the internal hexagonal portion of the implant. The aim of the
      present research was to compare fluids and bacterial penetration in 2 different
      implant systems, one with cement-retained abutments (CRA) and the other with
      screw-retained abutments (SRA). METHODS: Twelve CRA dental implants and 12 SRA
      implants were used in this study. The research was done in 3 steps: scanning
      electron microscopic (SEM) analysis, fluid penetration analysis, and bacterial
      penetration analysis. RESULTS: 1) Under SEM it was possible to observe in the SRA
      implants a mean 2 to 7 micron gap between implant and abutment, while in the CRA
      implants, the gap was 7 micron. In the latter group, however, the gap was always
      completely filled by the fixation cement. All the spaces between abutment and
      implant were filled by the cement. 2) With SRA implants, it was possible to
      observe the presence of toluidine blue at the level of the fixture-abutment
      interface and the internal threads; the absorbent paper was stained in all cases.
      With CRA implants, the absorbent paper inside the hollow portion of the implants
      was never stained by toluidine blue. No penetration of toluidine blue was
      observed at the implant-abutment interface and inside the hollow portion of the
      implants. 3) In all the SRA implant assemblies, bacterial penetration was
      observed at the implant-abutment interface. No bacteria were detected in the
      hollow portion of the CRA implants. CONCLUSION: On the basis of the results
      obtained in the present study using 2 different implant systems, we conclude that
      CRA implants offer better results relating to fluid and bacterial permeability
      compared to SRA implants.

PMID- 11577945
TI  - Interaction between piroxicam and azithromycin during distribution to human
      periodontal tissues.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs and antibiotics are important
      in the prevention of infections and pain associated with periodontal surgery as
      well as in the adjunctive therapy of periodontal disease. In this study, patients
      undergoing oral surgery were treated with piroxicam and azithromycin to examine
      the interactions of these drugs on periodontal tissues. METHODS: Sixty-six
      patients were assigned to 3 groups and treated for 3 days as follows: 1)
      piroxicam 20 mg/day; 2) azithromycin 500 mg/day; or 3) piroxicam 20 mg/day plus
      azithromycin 500 mg/day. Samples of blood, saliva, gingiva, and alveolar bone
      were collected during surgery and at days 0.5, 2.5, 4.5, and 6.5 after last dose.
      Piroxicam concentrations were assayed by high-performance liquid chromatography
      and azithromycin concentrations by microbiological assay. RESULTS: In patients
      treated with piroxicam alone, the highest drug concentrations were found in
      plasma at each time point, but consistent piroxicam levels were also detected in
      gingival samples up to 4.5 days. The combined treatment with piroxicam plus
      azithromycin was associated with a reduction of piroxicam concentrations in
      periodontal tissues. In patients receiving azithromycin alone, high drug levels
      were measured in periodontal tissues up to 6.5 days. This distribution pattern
      did not vary in patients treated with piroxicam plus azithromycin. CONCLUSIONS:
      Treatment with piroxicam or azithromycin alone ensures a favorable distribution
      of these drugs into periodontal tissues. However, upon combined administration,
      azithromycin interferes negatively with the periodontal disposition of piroxicam.
      This interaction might depend on the displacement of piroxicam from acceptor
      sites at the level of periodontal tissues.

PMID- 11577946
TI  - The use of bovine porous bone mineral in combination with enamel matrix proteins
      or with an autologous fibrinogen/fibronectin system in the treatment of intrabony
      periodontal defects in humans.
AB  - BACKGROUND: Enamel matrix derivative (EMD) and autologous fibrinogen/fibronectin
      system (AFFS) are agents that have been shown to be effective in periodontal
      regeneration. Their use in combination with graft materials, however, has not
      been extensively examined. The purpose of this study was to compare the clinical
      effectiveness of bovine porous bone mineral (BPBM) used in combination with an
      EMD or in combination with AFFS as regenerative treatments for periodontal
      intrabony defects in humans. METHODS: Twenty-three paired intrabony defects were
      surgically treated using a split mouth design. Defects were treated with BPBM
      either combined with EMD (BPBM/EMD) or with AFFS (BPBM/AFFS). The clinical
      parameters evaluated included changes in attachment level, probing depth, and
      defect fill as revealed by re-entry surgeries at 6 months. RESULTS: Preoperative
      probing depths, attachment levels, and transoperative bone measurements were
      similar for the 2 treatment groups. Postsurgical measurements taken at 6 months
      revealed that both treatment modalities resulted in clinically and statistically
      significant improvements in probing depth resolution, clinical attachment gain,
      and defect fill as compared to baseline. Both therapy modalities improved
      clinical parameters as compared to baseline, but the differences found between
      the groups were not statistically significant. CONCLUSIONS: The results of this
      study indicate that EMD and AFFS used in combination with BPBM have similar
      effects in promoting probing depth reduction, clinical attachment gain, and
      defect fill when employed as regenerative therapy for intraosseous lesions in
      humans. A study involving a larger sample size is necessary to statistically
      confirm the equivalence between the 2 treatment modalities.

PMID- 11577947
TI  - An "S-shaped" relationship between smoking duration and alveolar bone loss:
      generating a hypothesis.
AB  - BACKGROUND: A number of epidemiological studies have shown that smoking is a risk
      factor for periodontal disease. Little is known about the relationship between
      smoking duration and alveolar bone loss. The purpose of this research was to
      describe the prevalence of alveolar bone loss according to smoking status in
      Norway. A dose-response model for duration of tobacco smoking on alveolar bone
      loss was then developed and discussed. METHODS: The study population consisted of
      812 individuals living in Norway aged 45 to 64 years old (248 current smokers,
      245 former smokers and 319 non-smokers). Alveolar bone loss was measured on bite
      wing radiographs. Simple descriptive statistics were used to describe the central
      tendency and variation in alveolar bone loss. Regression analyses were performed
      to study the relationship between smoking duration and alveolar bone loss.
      RESULTS: Mean alveolar bone loss varied between 1.51 mm and 2.64 mm depending on
      smoking status and age. Mean alveolar bone loss was lowest in non-smokers and
      highest in current smokers. Given identical smoking status, the mean alveolar
      bone loss increased with increasing age except for the 2 oldest age groups of
      current smokers. CONCLUSIONS: Our results generate the hypothesis that the
      relationship between smoking duration and alveolar bone loss was "S-shaped."
      Assuming that alveolar bone loss is irreversible after smoking cessation, it
      could be hypothesized that there is a threshold period for tobacco smoking after
      which the accumulated effect of smoking becomes clinically observable. After a
      certain number of years of smoking, the effect on alveolar bone loss seems to
      level out. To test this hypothesis, the relationship between smoking duration and
      alveolar bone loss should be studied in a prospective study design.

PMID- 11577948
TI  - Effects of whole cell sonicates of Treponema lecithinolyticum on osteoclast
      differentiation.
AB  - BACKGROUND: Alveolar bone destruction is a characteristic feature of periodontal
      diseases and multinucleated osteoclast cells derived from hemopoietic cells are
      responsible for bone resorption. Treponema lecithinolyticum is a novel oral
      spirochete isolated from the periodontal lesions. METHODS: The effect of whole
      cell sonicates on the osteoclast differentiation was examined in a co-culture
      system of hemopoietic mouse bone marrow cells and calvaria derived-osteoblastic
      cells to clarify the role of T. lecithinolyticum in the alveolar bone destruction
      associated with periodontal diseases. The differentiated osteoclasts were
      confirmed by tartrate-resistant acid phosphatase (TRAP) staining. RESULTS:
      Sonicates of this bacterium stimulated the osteoclast formation in the co-culture
      system in a dose-dependent manner. The sonicates-induced osteoclast formation was
      partially inhibited by the heat treatment of sonicates. Indomethacin, which is a
      prostaglandin inhibitor, decreased the osteoclast formation induced by the
      bacterial sonicates. CONCLUSIONS: These findings suggest that T. lecithinolyticum
      induces osteoclast differentiation by a prostaglandin E2-dependent mechanism and
      that heat-labile components may be involved in this process.

PMID- 11577949
TI  - Effects of erbium,chromium:YSGG laser irradiation on canine mandibular bone.
AB  - BACKGROUND: Only relatively few reports have described the morphological effects
      on bone produced by erbium,chromium: yttrium,scandium,gallium,garnet (Er,Cr:YSGG)
      laser irradiation, and none has investigated the atomic changes or estimated the
      temperature increases involved. The objectives of this study were to investigate
      the morphological, atomic, and temperature changes in irradiated areas during and
      after laser irradiation, and to evaluate the cutting effect on canine mandibular
      bone in vitro. METHODS: Two canine mandibular bones were cut into 3 to 5 cm
      pieces and irradiated by an Er,Cr:YSGG laser utilizing a water-air spray at 5 W
      and 8 Hz for 10 or 30 seconds. During and after laser irradiation, temperature
      increases in the irradiated areas were measured by thermography. The samples were
      then observed by stereoscopy and scanning electron microscopy to determine
      morphological changes and by energy dispersive x-ray spectroscopy to evaluate
      atomic alterations. RESULTS: Regular holes or grooves having sharp edges and
      smooth walls were produced, but no melting or carbonization was observed. The
      maximum temperature increase was an average 12.6 degrees C for 30-second
      irradiation. The continuous time of a temperature increase of more than 10
      degrees C was consistently less than 10 seconds. An atomic analytical examination
      revealed that the calcium:phosphorus ratio was not significantly changed between
      the lased and unlased areas (P>0.0 1). CONCLUSION: These results showed that the
      Er,Cr:YSGG laser cuts canine mandibular bone effectively without burning,
      melting, or altering the calcium:phosphorus ratio of the irradiated bone.

PMID- 11577950
TI  - Effect of different mouthrinses on morning breath.
AB  - BACKGROUND: Morning breath odor is an often-encountered complaint. This double
      blind, crossover, randomized study aimed to examine the bad breath-inhibiting
      effect of 3 commercially available mouthrinses on morning halitosis during an
      experimental period of 12 days without mechanical plaque control. METHODS: Twelve
      medical students with a healthy periodontium refrained from all means of
      mechanical plaque control during 3 experimental periods of 12 days (with
      intervening washout periods of at least 3 weeks). A professional oral cleaning
      preceded each period. During each experimental period, as the only oral hygiene
      measure allowed, the students rinsed twice a day with one of the following
      formulations in a randomized order: CHX-Alc (a 0.2% chlorhexidine [CHX]
      solution); CHX-NaF (CHX 0.12% plus sodium fluoride 0.05%); or CHX-CPC-Zn (CHX
      0.05% plus cetylpyridinium chloride 0.05% plus zinc lactate 0.14%). After 12
      days, morning breath was scored via volatile sulfur compound (VSC) level
      measurements of the mouth air and organoleptic ratings of the mouth air, the
      expired air, and a scraping of the tongue coating. At the 12-day visit, a
      questionnaire (subjective ratings) was completed and samples taken from both the
      tongue coating and the saliva for anaerobic and aerobic culturing and vitality
      staining. The de novo supragingival plaque formation was also recorded. All
      parameters were correlated with the baseline registrations. RESULTS: Although
      oral hygiene during the 3 experimental periods was limited to oral rinses, bad
      breath parameters systematically improved, with the exception of a slight
      increase in VSC levels while using CHX-Alc, a finding which was associated with
      the direct influence of the CHX on the sulfide monitor. The oral microbial load
      after the use of CHX-NaF remained unchanged, while for the CHX-Alc and CHX-CPC
      Zn, significant reductions in both aerobic and anaerobic colony forming units
      (CFU)/ml were noticed in comparison with baseline data for both tongue coating
      and saliva samples. The composition of microflora, on the other hand, did not
      reveal significant changes. The supragingival plaque formation was inhibited, in
      descending order, by CHX-Alc, CHX-CPC-Zn, and CHX-NaF. The subjective scores for
      the rinses indicated a higher appreciation for CHX-CPC-Alc and CHX-NaF because of
      a better taste and fewer side effects. CONCLUSIONS: The results of this study
      demonstrate that morning halitosis can be successfully reduced via daily use of
      mouthrinses. CHX-Alc and CHX-CPC-Zn mouthrinses result in a significant reduction
      of the microbial load of tongue and saliva.

PMID- 11577951
TI  - The effect of hyaluronan on bone and soft tissue and immune response in wound
      healing.
AB  - BACKGROUND: The aims of this study were to investigate the anti-inflammatory
      effect and the effect on bone regeneration of hyaluronan in surgical and non
      surgical groups. METHODS: In each of 15 individuals, 2 teeth with defects of
      similar character and magnitude in the upper or lower jaw were chosen. There were
      at least 2 teeth between the test and the control sites. In the surgical group, a
      bioabsorbable membrane was used for both test and control sites, and hyaluronan
      was placed in the intrabony pocket of the test site. In the non-surgical group,
      the periodontal pockets were scaled and hyaluronan was administered 3 times with
      an interval of 1 week in the test pockets. Alveolar bone height and bone healing
      patterns were analyzed using digital intraoral radiographs. Measurements of bone
      height were performed in the original digital black-and-white radiographs to
      obtain quantitative data on bone gain or loss. Bone healing patterns were studied
      with color-coded radiographs, using specially designed software in a personal
      computer with subsequent combinations of radiographs. Gingival crevicular fluid
      immunoglobulin (Ig)G, C3, and prostaglandin E2 (PGE2) responses; periodontal
      probing depth; bleeding on probing; and the presence of plaque were studied to
      evaluate the anti-inflammatory effect. Data were obtained at baseline before
      treatment, and at 2 weeks, and 1, 3, 6, and 12 months after treatment. RESULTS:
      For the surgical treatments, bone height was increased in the test group treated
      with hyaluronan (mean value 2.2%, corresponding to an average increase of
      approximately 0.5 mm) and reduced in the control group (mean value -1.8%,
      corresponding to an average decrease of approximately - 0.4 mm) (P<0.05) after 12
      months. For the non-surgical treatments, bone height was reduced by a mean value
      of -1.1% (corresponding to an average decrease of approximately -0.25 mm) in the
      test group treated with hyaluronan and -3.3% (corresponding to an average
      decrease of approximately -0.75 mm) in the control group after 12 months (N.S.).
      According to the digital color-coded radiographs, the test sites in the surgical
      and non-surgical groups showed apposition of bone minerals. Immune responses
      showed no differences during the 12 months studied for the surgical and non
      surgical sites. Mean periodontal probing depths were reduced between 2.5 mm and
      4.1 mm in the surgical and non-surgical groups. CONCLUSIONS: The observed
      difference in bone height between test and control sites in the surgical group
      after 12 months was less than 1 mm, which was only detectable on radiographs. No
      statistical difference was found on radiographs in the non-surgical group, where
      a decrease in bone height was found for both groups after scaling. Probing depth
      reduction after the surgical treatment, as well as after scaling and root
      planing, was as expected. Hyaluronan in contact with bone and soft tissues had no
      influence on the immune system in this study. Further studies are needed to
      determine the extent to which hyaluronan can lead to clinically significant
      healing of periodontal lesions.

PMID- 11577952
TI  - Performance of a commercial immunoassay for detection and differentiation of
      periodontal marker bacteria: analysis of immunochemical performance with clinical
      samples.
AB  - BACKGROUND: We employed a commercial immunoassay for simultaneous detection and
      differentiation of marker bacteria Actinobacillus actinomycetemcomitans,
      Porphyromonas gingivalis, and Prevotella intermedia and reassessed the
      immunochemical performance of the assay. METHODS: We compared the analytical
      performance of the immunoassay in our study of clinical samples from 249
      periodontal patients in 2 private periodontal practices with the previously
      reported analytical performance of the same immunoassay. We also compared
      immunoassay measurements of the marker bacteria in clinical samples with values
      obtained in other studies by direct culture of the same organisms. RESULTS: The
      assay produced 3 times more high-end readings than reported previously. We also
      reassessed and revised previously published calibration curves for the
      immunoassay. The immunoassay provided measurements of the marker bacteria in
      clinical samples from our patients that were comparable to and consistent with
      measurements of the same bacteria by direct culture in other studies.
      CONCLUSIONS: We ascribe the increased sensitivity of the immunoassay in our study
      to: 1) a more standardized and vigorous sample dispersion that improves release
      of particulate and soluble antigens from dental plaque biofilm, and 2) better
      visualization of the reaction product of the enzyme-linked immunoassay. High
      technology assays, such as diagnostic immunoassays, have a significant potential
      for future development in dental diagnosis, because they simplify detection and
      measurement of biologically important markers such as specific bacteria in
      clinical samples. Commercial assays also have an important potential for
      standardization of clinical measurements of biological markers.

PMID- 11577953
TI  - Effects of smoking and treatment status on periodontal bacteria: evidence that
      smoking influences control of periodontal bacteria at the mucosal surface of the
      gingival crevice.
AB  - BACKGROUND: We examined whether smoking status could influence growth of
      potentially pathogenic bacteria in the periodontal environment of treated and
      untreated periodontal patients. METHODS: We have previously reported effects of
      treatment status on marker bacteria in our patients. We established a history of
      any smoking during 6 months prior to microbiological sampling (F-ME, 16 smokers
      out of 64; MHM, 70 smokers out of 185). We used a commercial immunoassay to
      quantitate Porphyromonas gingivalis, Prevotella intermedia, and Actinobacillus
      actinomycetemcomitans in paper point samples from periodontal sites. RESULTS:
      Logistic regression showed that in smokers, neither P. gingivalis nor A.
      actinomycetemcomitans was quantitatively increased, while P intermedia was
      somewhat increased. Multiple regression demonstrated that smoking disrupts the
      positive relationship between increasing probing depth and increasing bacterial
      growth that is found in non-smokers. In smokers, growth of marker bacteria at
      shallow sites (< or =5 mm) was significantly increased to the levels found at
      deeper sites (>5 mm) in both smokers and non-smokers. Supragingival plaque
      biofilm was identified as a reservoir for marker bacteria; smokers and nonsmokers
      had equal ranges of oral cleanliness. CONCLUSIONS: Smoking-associated
      periodontitis is not simply a reflection of oral cleanliness. Smoking extends a
      favorable habitat for bacteria such as P. gingivalis, P. intermedia, and A.
      actinomycetemcomitans to shallow sites (< or =5 mm). Molecular byproducts of
      smoking interfere with mechanisms that normally contain growth of damaging
      bacteria at the surface of the oral mucosa in gingival crevices. In this way,
      smoking can promote early development of periodontal lesions.

PMID- 11577954
TI  - Periodontal infections contribute to elevated systemic C-reactive protein level.
AB  - BACKGROUND: Periodontitis is a local inflammatory process mediating destruction
      of periodontal tissues triggered by bacterial insult. However, this disease is
      also characterized by systemic inflammatory host responses that may contribute,
      in part, to the recently reported higher risk for cardiovascular disease (CVD)
      among patients with periodontitis. Moderate elevation of C-reactive protein (CRP)
      has been found to be a predictor of increased risk for CVD. Elevated CRP levels
      in periodontal patients have been reported by several groups. In this study, we
      examined whether CRP plasma levels are increased in periodontitis and if there is
      a relation to severity of periodontal disease and to the periodontal microflora.
      METHODS: CRP serum levels were assessed using radial immunodiffusion assay in 174
      subjects, 59 with moderate mean clinical attachment loss (AL) (2.39+/-0.29 mm)
      and 50 with high AL (3.79+/-0.86 mm) as compared to 65 periodontally healthy
      controls (AL, 1.74+/-0.18 mm). Clinical attachment loss, probing depths, and
      percentage of periodontal pocket sites > or =5 mm were measured. The presence of
      periodontal pathogens Porphyromonas gingivalis (P.g.), Prevotella intermedia
      (P.i.), Campylobacter recta (C.r.), and Bacteroides forsythus (B.f.) in
      subgingival plaque samples was measured by immunofluorescence microscopy.
      RESULTS: Statistically significant increases in CRP levels were observed in
      subjects with periodontal disease when compared to healthy controls (P= 0.036).
      Subjects with high levels of mean clinical attachment loss had significantly
      higher mean CRP levels (4.06+/-5.55 mg/l) than controls (1.70+/-1.91 mg/l), P=
      0.011. The CRP levels were adjusted for factors known to be associated with
      elevated CRP, including age, smoking, body mass index (BMI), triglycerides, and
      cholesterol. Age and BMI were found to be significant covariates. The reported
      range for CRP as a risk factor for CVD, peripheral vascular diseases, or stroke
      is 1.34 mg/l to 6.45 mg/l and the mean of this range is 3 mg/l. The percentage of
      subjects with elevated levels of CRP > or = 3 mm was significantly higher in the
      high clinical AL group (38%; 95% Cl: 26.7%, 49.3%) when compared to the control
      group (16.9%; 95% CI: 9.25%, 24.5%), P= 0.011. The presence of periodontal
      pathogens P.g., P.i., C.r., and B.f. in subgingival samples was positively
      associated with elevated CRP levels (P= 0.029). CONCLUSIONS: The extent of
      increase in CRP levels in periodontitis patients depends on the severity of the
      disease after adjusting for age, smoking, body mass index, triglycerides, and
      cholesterol. Also, there are elevated levels of CRP associated with infection
      with subgingival organisms often associated with periodontal disease, including
      P.g., P.i., C.r., and B.f. Recent investigations emphasized the role of moderate
      elevated CRP plasma levels as a risk factor for CVD. The positive correlation
      between CRP and periodontal disease might be a possible underlying pathway in the
      association between periodontal disease and the observed higher risk for CVD in
      these patients.

PMID- 11577955
TI  - A sensitive method for detecting Porphyromonas gingivalis by polymerase chain
      reaction and its possible clinical application.
AB  - BACKGROUND: It is useful for the clinical diagnosis of periodontitis to monitor
      the colonization of periodontopathic bacteria in periodontal pockets. In this
      study, we attempted to establish and possibly identify the clinical application
      of a sensitive method to detect Porphyromonas gingivalis (P.g.), one of the
      putative periodontopathic bacteria related to chronic periodontitis. METHODS:
      Genomic DNA extracted from cultured P.g. 381 and clinically isolated subgingival
      plaque samples were used as a template of polymerase chain reaction (PCR). We
      designed primers to amplify the genomic DNA coding 40 kDa outer membrane protein
      (OMP), one of the unique proteins to all strains of P.g. The efficiency and
      specificity of amplification were evaluated by agarose gel electrophoresis and
      subsequent Southern hybridization with a digoxygenin-labeled oligonucleotide
      probe. RESULTS: Fewer than 100 P.g. bacterial cells in the specimen were
      reproducibly detected by PCR-hybridization assay. This PCR-hybridization assay
      was at least 100 times more sensitive than the conventional indirect
      immunofluorescence assay (IIF). Furthermore, the imaging analysis showed that
      there is a linear correlation between the strength of the signal and the cell
      number of P.g. from which the template DNA was extracted semiquantitatively. It
      is noteworthy that the PCR assay could also be applied to detect P.g. from
      clinical plaque samples and that it was approximately 100 times more sensitive
      than a conventional IIF assay. CONCLUSION: The PCR assay established in this
      study can be a powerful tool to detect P.g. in periodontal pockets and monitor
      the colonization and/or recolonization of P.g. at the very early phase.

PMID- 11577956
TI  - Periodontal changes in liver cirrhosis and post-transplantation patients. I:
      clinical findings.
AB  - BACKGROUND: Cyclosporin A (CsA) is widely used to prevent liver transplantation
      failure. CsA-induced gingival overgrowth is a common side effect. However, the
      effect of cirrhotic liver disease, liver transplantation, and immunosuppressive
      therapy on the periodontium is yet unclear. The aim of the present cross
      sectional study was to examine the effect of liver cirrhosis, transplantation,
      and immunosuppressive therapy on the periodontium. METHODS: The experimental
      group (LC) consisted of 13 liver cirrhosis patients. A second experimental group
      (PT) included 24 patients, post-liver transplantation, receiving
      immunosuppressive therapy. Seventeen healthy subjects formed a control group. The
      Ramfjord index teeth were recorded for plaque index (PI), gingival index (GI),
      probing depth (PD), clinical attachment level (CAL), and gingival overgrowth
      (GO). RESULTS: Mean PI and mean GI for the LC, PT, and C groups were not
      statistically different (P >0.05). Mean PD for the LC (3.32+/-0.24 mm) and PT
      group (3.41+/-0.13 mm) was significantly higher (P = 0.0001, ANOVA) compared to
      the C group (2.45+/-0.16 mm). Likewise, CAL for the LC (4.89+/-0.47 mm) and PT
      group (4.68+/-0.47 mm) was significantly higher (P = 0.001, ANOVA) than the C
      group (2.78+/-0.23 mm). Patients in the PT group exhibited the greatest mean GO
      scores (0.88+/-0.09) compared to the LC group (0.37+/-0.07) and the C group
      (0.09+/-0.02). All 3 groups were significantly different from each other (P =
      0.0001) despite great variability within the groups. GO in the CsA-treated
      patients (1.1+/-0.09) was significantly higher (P = 0.0001) than in those treated
      with tacrolimus (0.57+/-0.1). CONCLUSIONS: Liver cirrhosis patients demonstrated
      greater pocketing and attachment loss compared to healthy matched controls. These
      same differences were observed in patients post-transplantation. Gingival
      overgrowth occurred as a result of the immunosuppressive therapy with CsA, while
      to a lesser degree with tacrolimus. Replacement of CsA by tacrolimus in patients
      manifesting gingival overgrowth might be recommended whenever possible to
      overcome this problem.

PMID- 11577957
TI  - Local versus systemic adjunctive antibiotic therapy in 28 patients with
      generalized aggressive periodontitis.
AB  - BACKGROUND: Although the use of systemic antibiotics has been studied in patients
      with generalized aggressive periodontitis (formerly rapidly progressive
      periodontitis), the use of adjunctive tetracycline fibers in these patients has
      not been reported. The purpose of the present study was to compare the clinical
      response of local versus systemic antibiotic treatment as adjuncts to scaling and
      root planing in patients with GAgP. METHODS: After initial therapy and full-mouth
      scaling and root planing (SRP), 30 patients were randomly assigned to 1 of 2
      antibiotic treatment groups. Probing depth (PD), clinical attachment level (CAL),
      and bleeding on probing (BOP) were recorded with an automated probe prior to SRP
      at baseline (BL) and 15, 30, 41, and 54 weeks later. Three months after SRP, the
      patients were treated with amoxicillin/clavulanic acid (500 mg tid; SRP + AUG
      group) or with local tetracycline fiber in pockets with PD > or =5 mm (SRP + TCF
      group). RESULTS: In both treatment groups, PD decreased significantly from BL to
      week 54 (6.2+/-1.5 mm to 4.7+/-1.4 mm for SRP + TCF and 6.5+/-1.4 mm to 4.2+/-0.6
      mm for SRP + AUG). However, there was no statistically significant difference
      between the 2 groups in pocket reduction. Similarly, in both treatment groups,
      there were small but significant gains in CAL from BL to week 54 (12.0+/-1.8 mm
      to 11.3+/-1.8 mm for SRP + TCF and 12.3+/-1.5 mm to 11.2+/-1.2 mm for SRP + AUG).
      The difference in CAL gain between the 2 groups was not statistically
      significant. At the final examination, both groups showed significant PD
      reduction and CAL gain (P <0.001) compared to BL. The frequency and percentage of
      bleeding sites decreased significantly in both groups. At week 54, this decrease
      was significantly greater in the SRP + AUG group (31.67% for SRP + TCF versus
      3.85% for SRP + AUG). CONCLUSIONS: These results indicate that the local delivery
      of tetracycline by a fiber or the systemic administration of
      amoxicillin/clavulanic acid given 3 months after scaling and root planing
      produced similar clinical outcomes over the 9-month observation period.

PMID- 11577958
TI  - Health behaviors and their relation to metabolic control and periodontal status
      in type 2 diabetic patients: a model tested using a linear structural relations
      program.
AB  - BACKGROUND: Although it has been reported that diabetic control is beneficial in
      managing periodontal disease, there are few studies in the literature where the
      relationship between singular behavioral factors and periodontal status has been
      examined. The aim of this study was to examine the simultaneous
      interrelationships among selected medical/dental variables and 5 behavior
      components with general health behavior (GHB), perceived fatigue (PF), diet
      control (DC), regular diet (RD), and dental behavioral inventory (HU-DBI) scores,
      using data from a study of 102 type 2 diabetic patients. METHODS: A hypothesized
      model was tested by a linear structural relations program (LISREL). RESULTS:
      There was a significant correlation between oral health behavior and calculus
      accumulation (r = 0.399; P<0.001). Correlations were found between calculus and
      periodontal status measured by gingivitis index and probing depth (r = 0.232;
      P<0.05, r = 0.279; P<0.01, respectively). The final model was found to be
      consistent with the data (chi2 = 55.0, df = 47, P = 0.197; GFI = 0.922). Oral
      health behavior affected periodontal status through its effect on calculus but
      not plaque accumulation. General health behavior had significant effects on oral
      health behavior and diet behavior (P<0.05 and P<0.001, respectively). Diet
      behavior affected both plaque accumulation and metabolic control (P<0.05 and
      P<0.01, respectively). However, the result was the virtual absence of a
      significant pass coefficient between metabolic control and periodontal status.
      CONCLUSIONS: The severity of the 2 diseases seemed to be connected indirectly
      through health behaviors such as diet behavior and oral health behavior.

PMID- 11577959
TI  - Leptin within healthy and diseased human gingiva.
AB  - BACKGROUND: Plasma leptin concentrations are reported to be elevated in patients
      with inflammatory diseases. There is no consensus concerning the biological
      mechanism for this phenomenon. To date, tissue leptin concentrations have not
      been assessed within normal or inflamed gingiva. The purpose of this study was to
      assess concentrations of human leptin within healthy and diseased gingiva to
      define its possible role in periodontal disease progression. METHODS: Healthy
      (non-hemorrhagic gingiva adjacent to a < or =3 mm gingival sulcus) and inflamed
      gingiva (hemorrhagic gingiva adjacent to a > or =3 mm periodontal pocket) were
      studied. Leptin, vascular endothelial growth factor (VEGF; to assess potential
      vascular expansion), and interleukin-6 (IL-6; to assess periodontal disease
      activity and severity) concentrations were assessed within solubilized gingival
      biopsies by enzyme-linked immunosorbent assay. Data were grouped by sulcular
      depth and compared by factorial analysis of variance, regression analysis, and
      Scheffe comparisons. RESULTS: Leptin concentrations were highest within gingiva
      adjacent to a < or =3 mm sulcus and progressively declined within gingiva
      adjacent to a > or =3 mm sulcus. VEGF concentrations were highest within gingiva
      adjacent to 4 to 6 mm pockets and nearly equivalent in healthy (< or =3 mm
      sulcus) and severely diseased gingiva (>6 mm sulcus). IL-6 was positively
      correlated and leptin negatively correlated with adjacent probing depth; IL-6
      concentration was significantly higher and leptin significantly lower in gingiva
      adjacent to >6 mm pockets compared to sites adjacent to <6 mm pockets (P<0.001).
      CONCLUSIONS: Human leptin is present within healthy and marginally inflamed
      gingiva and decreases in concentration as the adjacent probing depth increases.
      When leptin concentrations decreased (> or =3 mm sulcus), VEGF concentrations
      increased, suggesting that leptin could be released from gingiva coincident to
      vascular expansion. Thus, gingiva, in addition to adipose tissue, could be a
      source of circulating leptin in patients with periodontal disease. This
      possibility requires further investigation.

PMID- 11577960
TI  - Comparative clinical study of guided tissue regeneration with a bioabsorbable
      bilayer collagen membrane and subepithelial connective tissue graft.
AB  - BACKGROUND: During the last decade, there have been great strides in the
      treatment of gingival recession defects, especially with subepithelial connective
      tissue graft and guided tissue regeneration (GTR) procedures. Gingival recession
      represents a significant concern for patients. It is necessary to choose the most
      appropriate procedure in order to obtain more root coverage while avoiding
      clinical disadvantages. The purpose of this randomized clinical trial was to
      evaluate the use of a bioabsorbable bilayer collagen membrane with GTR compared
      to a connective tissue graft in the treatment of gingival recession defects.
      METHODS: Twenty patients each contributing a pair of Miller Class I or II buccal
      gingival recessions were treated. In each pair, one recession was randomly
      assigned for treatment with GTR using a bioabsorbable bilayer collagen membrane
      and the other treated with subepithelial connective tissue graft (CTG). Clinical
      measurements taken at baseline (D0) and 3 and 6 months post-treatment included
      recession depth (RD), recession width (RW), probing depth (PD), and clinical
      attachment level (CAL). RESULTS: Data were analyzed using the non-parametric
      Wilcoxon matched pair test. All results were statistically significant. Both
      treatments resulted in a significant gain of root coverage (P<0.0001), amounting
      to an average of 2.80 mm at 3 months in the GTR group and 3.34 mm in the CTG
      group. At 6 months, the decrease of the mean RD remained statistically
      significant: 2.70 mm (74.59% root coverage) in the GTR group and 3.19 mm (84.84%
      root coverage) in the CTG group. The mean RW also decreased from 4.48 mm at D0 to
      2.42 mm at 6 months in the GTR group, and from 4.38 mm at D0 to 1.35 mm at 6
      months in the CTG group, representing a percentage of coverage of 45.98% and
      69.18%, respectively. Mean CAL gain obtained between D0 and 6 months with the GTR
      procedure and CTG was 3.31 mm and 3.09 mm, respectively, and was significant
      within groups. At 3 and 6 months, the differences in the results for RD, CAL, and
      RW were not statistically significant between the 2 groups. However, the
      difference was significant for PD at 3 and 6 months. CONCLUSIONS: The results
      suggest that a bioabsorbable bilayer collagen membrane can be used in the GTR
      treatment of human buccal recession defects, with no statistically significant
      differences between this procedure and connective tissue grafts.

PMID- 11577961
TI  - Localized aggressive periodontitis in a patient with type 1 diabetes mellitus: a
      case report.
AB  - BACKGROUND: Poor metabolic control of diabetes mellitus (DM) has often been
      associated with the severity of periodontal disease. The aim of this report is to
      present a 9-year-old female with localized aggressive periodontitis who had a
      history of type 1 DM and the outcome of her treatment. METHODS: The patient had
      received medical, clinical, and radiographic periodontal examinations. Peripheral
      blood analysis was done as well. She had non-surgical periodontal treatment, and
      medical management of her diabetes was performed at the same time. She was
      followed longitudinally for 5 years. RESULTS: Medical examination revealed no
      pathological findings except for growth retardation. Laboratory tests showed that
      she had poor metabolic control, with 497 mg/dl fasting blood glucose and 15.6%
      HbA1c. The random migration and neutrophil chemotaxis were significantly reduced.
      Periodontal treatment and metabolic control of her diabetes resulted in
      significant improvement in her periodontal condition. No incipient periodontal
      breakdown was observed around the teeth after 5 years from baseline. CONCLUSIONS:
      This report proves the efficiency of periodontal therapy in the prevention of
      future periodontal breakdown in a systemically compromised patient. It seems that
      in certain individuals who are predisposed to the aggressive forms of
      periodontitis, clinical and medical examinations and intervention to the systemic
      condition, in combination with periodontal treatment, are important in the
      management of these individuals.

PMID- 11577962
TI  - Oral Acanthosis nigricans as a marker of internal malignancy. A case report.
AB  - BACKGROUND: Acanthosis nigricans (AN) is a rare mucocutaneous condition that can
      involve the oral tissues. There are 2 clinical forms of AN: benign and malignant.
      Benign AN is related to systemic diseases such as diabetes and obesity or can be
      induced by drugs such as systemic corticosteroids, nicotinic acid, estrogens,
      insulin, and fusidic acid. Malignant AN appears in association with tumors such
      as lung, ovarian, breast, and gastric carcinoma. METHODS: A rare case of
      malignant AN that initially manifested in the oral cavity of a 73-year-old
      patient is reported. RESULTS: A bladder and lung carcinoma were detected
      following the diagnosis of AN. CONCLUSIONS: The diagnostic importance of oral AN
      is emphasized because, in our patient, its recognition led to the detection of 2
      occult malignant tumors.

PMID- 11577963
TI  - A bioengineered implant for a predetermined bone cellular response to loading
      forces. A literature review and case report.
AB  - The presence of fibrous tissue has long been known to decrease the long-term
      survival of a root-form implant. Excessive loads on an osseointegrated implant
      may result in mobility of the supporting device, and excessive loads may also
      fracture an implant component or body. Although several conditions may cause
      crestal bone loss, one of these may be prosthetic overload. Excessive loads on
      the bone cause strain conditions to increase. These microstrains on the bone may
      affect the bone remodeling rate in a direct relationship. When strain conditions
      to the interfacial bone are in the mild overload zone, an increased bone
      remodeling response occurs, which results in a reactive woven bone formation that
      is less mineralized and weaker. Greater stresses may cause the interfacial strain
      to reach the pathologic overload zone and may cause microfracture of the bone,
      fibrous tissue formation, and/or bone resorption. Recent reports suggest that the
      bone remodeling rate next to an implant may be used to evaluate biomechanical
      conditions and their influence on the implant-to-bone interface. These include a
      number of factors, such as loading conditions, implant body surface conditions,
      and implant design. For a given load condition, the implant design is one of the
      primary factors that determine the resultant strain at the interface. A
      predetermined goal was established to bioengineer a dental implant to load the
      bone at the interface in a predetermined stress strain relationship, in order to
      maintain lamellar bone at the interface. A case report is presented of 2
      bioengineered implants loaded for 1 year, which demonstrates that the bone was
      primarily lamellar in structure, the bone turnover rate was less than 5
      microns/day, and was the same as the bone away from the interface. These findings
      corroborate those observed in a prior animal study reported with the same implant
      design. Although the number of implants evaluated in those 2 reports is few, they
      support a predetermined histological outcome.

PMID- 11577964
TI  - Gingival plasma cell granuloma.
AB  - Plasma cell granulomas (pseudotumors) are rare benign, tumor-like proliferations
      composed chiefly of plasma cells that manifest primarily in the lungs, but may
      occur in various anatomic locations. We report this case of a 54-year-old male
      who presented with an unusual maxillary anterior gingival overgrowth treated by
      excisional biopsy. Histological examination revealed a dense inflammatory cell
      infiltrate containing mainly plasma cells. Immunohistochemistry for kappa and
      lambda light chains showed a polyclonal staining pattern confirming a diagnosis
      of plasma cell granuloma. Intraoral plasma cell granuloma is exceedingly rare,
      although case reports documenting such lesions have been reported. This case
      highlights the need to biopsy unusual lesions to rule out potential neoplasms.

PMID- 11577965
TI  - Re: Osseous defects: proper terminology revisited. Weinberg MA, Eskow RN
      (2000;71:1928).

PMID- 11577966
TI  - Re: The effect of occlusal discrepancies on periodontitis. I. Relationship of
      initial occlusal discrepancies to initial clinical parameters. Nunn NE, Harrel SK
      (2001;72:485-494). The effect of occlusal discrepancies on periodontitis. II.
      Relationship of occlusal treatment to the progression of periodontal disease.
      Harrel SK, Nunn ME (2001; 72:495-505).

PMID- 11577967
TI  - Further assessment of the construct validity of four measures of narcissism:
      replication and extension.
AB  - CT. The authors build on earlier research by L. S. Mullins and R. E. Kopelman
      (1988) and R. E. Kopelman and L. S. Mullins (1992) to reexamine the construct
      validity of four narcissism scales: the Margolis-Thomas Measure of Narcissism
      (MT; H. D. Margolis & V. A. Thomas, 1980), the Narcissistic Personality Disorder
      Scale (NPDS; H. U. Ashby, R. R. Lee, & E. H. Duke, 1979), the Narcissism
      Hypersensitivity subscale of the MMPI, Scale 5, Masculinity-Femininity (NHMF; K.
      Serkownek, 1975), and the Narcissistic Personality Inventory (NPI; R. Raskin & C.
      S. Hall, 1979). The present analysis included the revised NPI and its factors
      along with four measures of satisfaction and a number of other previously
      assessed variables. The MT exhibited the strongest validity, correlating
      positively with conceptually related constructs such as Machiavellianism,
      nonsignificantly with unrelated measures like the need to achieve, and inversely
      with all four satisfaction scales. Contrasts between the NPI and NPDS and NHMF
      seemed to parallel recent differentiations between overt and covert narcissism,
      but data for the NPI factors suggested instead that the four narcissism scales
      helped describe a complex psychological continuum related to adjustment.

PMID- 11577968
TI  - Identifying significant predictors of student evaluations of faculty through
      hierarchical regression analysis.
AB  - College teachers' ages and personalities, and students' course grades, gender,
      enrollment status, academic abilities, and ages were investigated as predictors
      of student evaluations of faculty. An evaluation form containing 7 items
      reflecting the personality trait of extraversion and 8 items reflecting teaching
      effectiveness was used to collect data from 351 undergraduates. Teachers'
      extraversion (.79) and teachers' ages (-.08) were correlated highest, and
      students' gender was correlated lowest (.08) with teaching effectiveness.
      Hierarchical regression revealed that teachers' extraversion was the only
      significant predictor of student evaluations (beta = .76, p < .001) after
      controlling for enrollment status, course grades, and student ages.

PMID- 11577969
TI  - Congruence of counselor self-disclosure and perceived effectiveness.
AB  - Sixty-seven college students rated a counselor on expertness, trustworthiness,
      and attractiveness based on reading 1 of 2 randomly assigned session transcripts.
      The desire to choose the depicted counselor was also measured. In both
      transcripts, the counselor self-disclosed his or her use of prayer. A single
      client statement varied across the 2 transcripts such that one contained a
      congruent counselor self-disclosure (counselor disclosure after client
      disclosure) and the other included an incongruent self-disclosure (counselor
      disclosure without client disclosure). A potential covariate, religiosity, was
      examined but did not draw significant variance. Participants in the congruent
      group reported a more favorable total perception, a higher attractiveness
      perception, and a greater desire to choose the counselor than did participants in
      the incongruent group. Limitations and implications for future research are
      discussed.

PMID- 11577970
TI  - Criminal offense type and the causes of loneliness.
AB  - This study is an examination of the influences of incarceration on perceived
      causes of loneliness. A heterogeneous prison population was divided into five
      homogeneous subgroups (sex offenders, violent offenders, property offenders, drug
      related offenders, and a category that contained all other miscellaneous
      offenders) whose loneliness experiences were then compared. Three hundred fifty
      six incarcerated male offenders and 501 men from the general population were
      recruited on a voluntary basis. They reported the perceived sources of their
      loneliness on an 82-item yes/no questionnaire. Results indicated significant
      differences in perceived causes of loneliness between the criminal and general
      populations and within the criminal sample when the data were examined according
      to offense type.

PMID- 11577971
TI  - Scaling satan.
AB  - The influence on social behavior of beliefs in Satan and the nature of evil has
      received little empirical study. Elaine Pagels (1995) in her book, The Origin of
      Satan, argued that Christians' intolerance toward others is due to their belief
      in an active Satan. In this study, more than 200 college undergraduates completed
      the Manitoba Prejudice Scale and the Attitudes Toward Homosexuals Scale (B.
      Altemeyer, 1988), as well as the Belief in an Active Satan Scale, developed by
      the authors. The Belief in an Active Satan Scale demonstrated good internal
      consistency and temporal stability. Correlational analyses revealed that for the
      female participants, belief in an active Satan was directly related to
      intolerance toward lesbians and gay men and intolerance toward ethnic minorities.
      For the male participants, belief in an active Satan was directly related to
      intolerance toward lesbians and gay men but was not significantly related to
      intolerance toward ethnic minorities. Results of this research showed that it is
      possible to meaningfully measure belief in an active Satan and that such beliefs
      may encourage intolerance toward others.

PMID- 11577972
TI  - A comparison of situational and dispositional predictors of perceptions of
      organizational politics.
AB  - The present study is an investigation of situational and dispositional
      characteristics that may predispose an employee to perceive his or her
      organization as political. Participants were 501 regular members, civilian
      members, and public servants of the Royal Canadian Mounted Police. Measures used
      for this research were the Formalization Scale (G. R. Oldham & J. R. Hackman,
      1981), the Job Autonomy Scale (H. P. Sims, A. D. Szilagyi, & R. T. Keller, 1976),
      the Mach IV (A. Zook & G. J. Sipps, 1986), the Dominance subscale from the
      Manifest Needs Questionnaire (R. M. Steers & D. N. Braunstein, 1976), the Survey
      of Organizational Climate (J. C. Taylor & D. G. Bowers, 1972), the Perceptions of
      Organizational Politics Scale (G. R. Ferris & K. M. Kacmar, 1992), and the Work
      Locus of Control Scale (P. E. Spector, 1988). Results indicated that
      organizational climate, formalization, work locus of control (both internal and
      external measures), and Machiavellianism were significant predictors, accounting
      for 52% of the variance in participants' perceptions of organizational politics.
      Limitations of the present study and directions for future research are outlined.

PMID- 11577973
TI  - Consensus change, conflict, and relationship satisfaction in romantic
      relationships.
AB  - In this cross-sectional study of 92 romantic relationships, both the S. S.
      Hendrick (1988) Relationship Assessment Scale and a 16-item negative conflict
      scale were independently associated with the consensus items of the Short Marital
      Adjustment Test (H. J. Locke & K. M. Wallace, 1959), but not with change from
      initial to present consensus. However, consensus change was significantly
      correlated with relationship satisfaction and negative conflict in those
      reporting decreased consensus or no change but not increased consensus.
      Furthermore, relationship satisfaction was accounted for solely by negative
      conflict in the increased consensus group and by present consensus in the
      decreased consensus group. These results suggest that the association of
      relationship satisfaction with consensus and negative conflict may differ
      according to perceived consensus change.

PMID- 11577974
TI  - A causal model of burnout among self-managed work team members.
AB  - The findings on burnout that are almost universally from research in service
      settings are applied to an industrial setting with self-managed work teams.
      Researchers formulated several hypotheses on the basis of this literature. These
      hypotheses were then used to develop a structural (causal) model that was tested
      and refined using LISREL 8. Data were collected from 320 employees concerning
      perceptions of several job and organization conditions, as well as the three
      components of burnout. Results indicated that role conflict contributed to
      emotional exhaustion, and participation in work teams diminished it. Job
      ambiguity, low co-worker support, and low job ability contributed to feelings of
      low personal accomplishment. These results were consistent with previous
      findings. When insufficient time to complete a job was removed from the workload
      measures, workload actually diminished burnout, a finding opposite from previous
      research. Other organization factors had no significant impact on burnout in this
      setting.

PMID- 11577975
TI  - Psychological correlates of attitudes toward men.
AB  - The relation between attitudes toward men and a number of personality, attitude,
      and health factors was studied. The 379 respondents (176 men, 203 women)
      completed the Attitudes Toward Men Scale (A. N. lazzo, 1983) and measures of the
      Big Five personality factors, conservatism, male bashing, attitudes toward women,
      sex role, locus of control, and health (including depression, anxiety, and self
      esteem). A regression analysis using correlates of attitudes toward men indicated
      that, among women, femininity and self-esteem were important in predicting
      attitudes toward men. Among men, masculinity, self-esteem, and age were most
      important in predicting attitudes toward men.

PMID- 11577976
TI  - Animal cellulases.
AB  - Previous dogma has maintained that cellulose, ingested by xylophagous or
      herbivorous animals, is digested by cellulolytic symbiotes. The first evidence in
      conflict with this contention involved the demonstration of cellulolytic
      activities in symbiote-free secreting organs (e.g., the salivary glands of
      termites) or defaunated guts. Following these demonstrations, possible endogenous
      cellulase components were purified from several cellulose-digesting
      invertebrates, but this research did little to change the general view concerning
      animal cellulose digestion. Thanks to recent developments in molecular biology,
      the existence of cellulases of animal origin has been firmly established. To
      date, cellulase genes have been reported from arthropods (insects and a crayfish)
      and nematodes. This paper describes and discusses the presence and nature of
      endogenous cellulases in higher animals.

PMID- 11577977
TI  - Lipopeptaibols, a novel family of membrane active, antimicrobial peptides.
AB  - Lipopeptaibols are members of a novel group of naturally occurring, short
      peptides with antimicrobial activity, characterized by a lipophilic acyl chain at
      the N-terminus, a high content of the turn/helix forming alpha-aminoisobutyric
      acid and a 1,2-amino alcohol at the C-terminus. The amino acid sequences range
      from 6 to 10 residues and the fatty acyl moieties from 8 to 15 carbon atoms. The
      peptide portion of lipopeptaibols can be shorter than those of the nonlipidated
      peptaibols that range from 10 to 19 amino acid residues. The longest peptides
      fold into a mixed 3(10)/alpha helix, whereas the shortest peptides tend to adopt
      a beta-turn/sheet structure. Using solution methodologies, a series of analogues
      of trichogin GA IV was synthesized which allowed determination of the minimal
      lipid chain and peptide main-chain lengths for the onset of membrane activity and
      exploitation of a number of spectroscopic techniques aimed at determining its
      preferred conformation under a variety of conditions and investigating in detail
      its mode of interaction with, and its effect on, the phospholipid membranes.

PMID- 11577978
TI  - Tetraspanins.
AB  - The first tetraspanins were discovered on surface of human leucocytes, but it was
      rapidly demonstrated that they had a wider tissue expression. Twenty-six
      molecules display sufficient homology to belong to the same superfamily. Their
      function is not precisely known, but data coming from biochemical studies or
      knockout mice suggest that they play a major role in membrane biology. One of
      their outstanding properties is their ability to form a network of multimolecular
      complexes, the 'tetraspanin web', in which integrins are included. The structure
      of these complexes is under investigation, but some of the rules that govern
      their organization have already been unraveled. The challenge is to determine how
      the organization of the 'tetraspanin web' modifies the function of its
      constitutive molecules and consequently influences cellular behaviour. The
      implications may be considerable for the understanding of basic cellular
      processes such as migration and also of diseases related to loss or mutation of a
      single tetraspanin.

PMID- 11577979
TI  - The prolactin releasing peptides: RF-amide peptides.
AB  - Although dopamine is considered the major hypothalamic controller of prolactin
      release from the anterior pituitary gland, there is evidence that a yet to be
      discovered prolactin releasing factor (PRF) also exists in brain. Recently, two
      peptides were isolated, products of the same prohormone, that were reported to
      have significant prolactin-releasing activity. These peptides, called prolactin
      releasing peptides, are not accepted by all investigators to be in fact PRFs.
      Instead, it appears that their widespread distribution in brain and the presence
      of receptors for the peptides in sites unrelated to neuroendocrine function are
      the basis for a variety of central nervous system action including activation of
      the autonomic nervous system. Thus, these peptides may not be PRFs, but instead
      neuroactive agents that are involved in many brain circuits with divergent
      functions.

PMID- 11577980
TI  - How do thermophilic proteins deal with heat?
AB  - Recent years have witnessed an explosion of sequence and structural information
      for proteins from hyperthermophilic and thermophilic organisms. Complete genome
      sequences are available for many hyperthermophilic archaeons. Here, we review
      some recent studies on protein thermostability along with work from our
      laboratory. A large number of sequence and structural factors are thought to
      contribute toward higher intrinsic thermal stability of proteins from these
      organisms. The most consistent are surface loop deletion, increased occurrence of
      hydrophobic residues with branched side chains and an increased proportion of
      charged residues at the expense of uncharged polar residues. The energetic
      contribution of electrostatic interactions such as salt bridges and their
      networks toward protein stability can be stabilizing or destabilizing. For
      hyperthermophilic proteins, the contribution is mostly stabilizing.
      Macroscopically, improvement in electrostatic interactions and strengthening of
      hydrophobic cores by branched apolar residues increase the enthalpy change
      between the folded and unfolded states of a thermophilic protein. At the same
      time, surface loop deletion contributes to decreased conformational entropy and
      decreased heat capacity change between the folded and unfolded states of the
      protein.

PMID- 11577981
TI  - Bromelain: biochemistry, pharmacology and medical use.
AB  - Bromelain is a crude extract from the pineapple that contains, among other
      components, various closely related proteinases, demonstrating, in vitro and in
      vivo, antiedematous, antiinflammatory, antithrombotic and fibrinolytic
      activities. The active factors involved are biochemically characterized only in
      part. Due to its efficacy after oral administration, its safety and lack of
      undesired side effects, bromelain has earned growing acceptance and compliance
      among patients as a phytotherapeutical drug. A wide range of therapeutic benefits
      has been claimed for bromelain, such as reversible inhibition of platelet
      aggregation, angina pectoris, bronchitis, sinusitis, surgical traumas,
      thrombophlebitis, pyelonephritis and enhanced absorption of drugs, particularly
      of antibiotics. Biochemical experiments indicate that these pharmacological
      properties depend on the proteolytic activity only partly, suggesting the
      presence of nonprotein factors in bromelain. Recent results from preclinical and
      pharmacological studies recommend bromelain as an orally given drug for
      complementary tumor therapy: bromelain acts as an immunomodulator by raising the
      impaired immunocytotoxicity of monocytes against tumor cells from patients and by
      inducing the production of distinct cytokines such as tumor necrosis factor-a,
      interleukin (Il)-1beta, Il-6, and Il-8. In a recent clinical study with mammary
      tumor patients, these findings could be partially confirmed. Especially promising
      are reports on animal experiments claiming an antimetastatic efficacy and
      inhibition of metastasis-associated platelet aggregation as well as inhibition of
      growth and invasiveness of tumor cells. Apparently, the antiinvasive activity
      does not depend on the proteolytic activity. This is also true for bromelain
      effects on the modulation of immune functions, its potential to eliminate burn
      debris and to accelerate wound healing. Whether bromelain will gain wide
      acceptance as a drug that inhibits platelet aggregation, is antimetastatic and
      facilitates skin debridement, among other indications, will be determined by
      further clinical trials. The claim that bromelain cannot be effective after oral
      administration is definitely refuted at this time.

PMID- 11577982
TI  - Reverse transcription of retroviruses and LTR retrotransposons.
AB  - Retroelements are mobile genetic entities that replicate via reverse
      transcription of a template RNA. A key component to the life cycle of these
      elements is the enzyme reverse transcriptase (RT), which copies the single
      stranded genomic RNA of the element into a linear double-stranded DNA that is
      ultimately integrated into the host genome by the element-encoded integrase. RT
      is a multifunctionnal enzyme which possesses RNA-dependent and DNA-dependent DNA
      polymerase activities as well as RNase H activity that specifically degrades the
      RNA strand of RNA-DNA duplexes. At some stages of the replication a strand
      displacement activity of RT is also necessary. All activities are essential for
      the conversion of single-stranded genomic RNA into the double-stranded
      preintegrative DNA. This review focuses on the role of RT in the different steps
      of the replication process of retroelements. The features of retrotransposon
      replication which differ from the retroviral ones will be emphasized. In a second
      part of the review, the biochemical and enzymatic properties of two newly
      characterized retrotransposon RTs will be described. The role of the integrase
      domain in reverse transcriptase activity of some retroviral and retrotransposon
      RTs will be discussed.

PMID- 11577983
TI  - Pre-menstrual steroids.
AB  - A number of steroid hormones and their metabolites fluctuate in the circulation
      across the human menstrual cycle. In addition to their classic actions on the
      hypothalamo-pituitary-gonadal axis, many of these hormones act as 'neuroactive
      steroids' to alter the function of neurotransmitters, such as GABA, within
      central nervous system circuits. Clinically, these steroids are important because
      they have not only acute but also long-term effects, and 'withdrawal' properties.
      This review discusses the effects of steroids such as 3alpha-OH-5alpha-pregnan-20
      one (3alpha,5alpha-THP or allopregnanolone) which alter GABA function in distinct
      ways dependent upon the time course of exposure, to either enhance or decrease
      inhibition in the brain. These effects are discussed in light of recent clinical
      findings which seek to further characterize the steroid milieu which underlies
      pre-menstrual dysphoria.

PMID- 11577984
TI  - Hepatitis C viral RNA: challenges and promises.
AB  - Hepatitis C virus (HCV), a positive-sense, single-stranded RNA virus of the
      Flaviviridae family, is a major cause of chronic hepatitis, liver cirrhosis, and
      hepatocellular carcinoma worldwide. Its RNA is difficult to study because
      biological materials are scarce and RNA replication is of low efficiency. This
      review focuses on the structure and functions of HCV RNA along with their
      biological and clinical significance. Despite the challenging characteristics of
      HCV, significant progress has been made in understanding the properties of HCV
      RNA and developing viral replication systems toward the improvement of antiviral
      therapies.

PMID- 11577985
TI  - Transcription factor GATA3 and the human HDR syndrome.
AB  - Recently, a member of the GATA-binding family of transcription factors was shown
      to be involved in the human hypoparathyroidism, sensorineural deafness and renal
      anomalies (HDR) syndrome. Deletion-mapping studies and subsequent mutation
      analysis revealed that haploinsufficiency for GATA3 is the underlying mechanism
      of the HDR syndrome. Here we discuss the clinical characteristics of the HDR
      syndrome and present an overview of the role of GATA3 and related GATA-binding
      transcription factors during vertebrate embryonic development and their
      involvement in human disease.

PMID- 11577986
TI  - The TSH receptor and its role in thyroid disease.
AB  - The thyrotropin (TSH) receptor plays a preeminent role in thyroid physiology and
      disease. TSH, acting through the TSH receptor, is the major stimulator of thyroid
      cell growth, differentiation and function. In Graves' disease, the TSH receptor
      is the target of stimulating antibodies that cause hyperthyroidism. Although
      still a topic of debate, the TSH receptor has been implicated in the pathogenesis
      of the endocrine ophthalmopathy associated with Graves' disease. Blocking
      antibodies against the TSH receptor are involved in the development of
      hypothyroidism in a subset of patients with autoimmune hypothyroidism.
      Transplacental passage of stimulating or blocking TSH receptor antibodies from a
      mother with autoimmune thyroid disease may result in transient hyper- or
      hypothyroidism in early infancy. During pregnancy, the placental hormone human
      choriogonadotropin (hCG) can cause gestational hyperthyroidism through cross
      reaction with the TSH receptor. Gestational hyperthyroidism may also be involved
      in the pathogenesis of hyperemesis gravidarum. Trophoblast tumors secreting hCG
      are a rare cause of hyperthyroidism. Somatic activating mutations of the TSH
      receptor have been identified as a molecular cause of toxic adenomas, whereas
      activating mutations in the germline give rise to nonautoimmune familial
      hyperthyroidism or sporadic congenital hyperthyroidism. These gain-of-function
      mutations are dominant, and one mutated allele is sufficient to result in
      disease. Inactivating germline mutations of both TSH receptor alleles lead to
      variable degrees of resistance to TSH, encompassing a spectrum ranging from
      euthyroid hyperthyrotropinemia to overt hypothyroidism with thyroid hypoplasia.

PMID- 11577987
TI  - N-terminal acetylation in a third protein family of vertebrate alcohol
      dehydrogenase/retinal reductase found through a 'proteomics' approach in enzyme
      characterization.
AB  - A recent finding of a novel class of retinol-active alcohol dehydrogenase (ADH)
      in frog prompted analysis of this activity in other vertebrate forms.
      Surprisingly, yet another and still more unrelated ADH was identified in chicken
      tissues. It was found to be a member of the aldo-keto reductase (AKR) enzyme
      family, not previously known as an ADH in vertebrates. Its terminal blocking
      group and the N-terminal segment, not assigned by protein and cDNA structure
      analysis, were determined by electrospray tandem mass spectrometry after protein
      isolation by two-dimensional gel electrophoresis. The N terminus is Acetyl-Ala-
      and the N-terminal segment contains two consecutive Asn residues. The results
      establish the new ADH enzyme of the AKR family and show the usefulness of
      combined gel separation and mass spectrometry in enzyme-characterization.

PMID- 11577988
TI  - Production of butyrylcholinesterase by Caco-2 cells: lack of relationship with
      triglyceride production.
AB  - Elevated levels of butyrylcholinesterase activity occur under a number of
      hypertriglyceridemic conditions, including diabetes and obesity. This study
      examines whether butyrylcholinesterase activity has a direct effect on
      triglyceride production, using Caco-2 cells, a human intestinal adenocarcinoma
      cell line. Caco-2 cells were incubated with 500 microM oleate to stimulate
      triglyceride production, and butyrylcholinesterase activity was measured in the
      cellular homogenate. Butyrylcholinesterase activity was approximately 3 x 10(-3)
      micromol/min per milligram protein. Although triglyceride production increased by
      almost five-fold after 18 h of stimulation with oleate, butyrylcholinesterase
      activity was not increased. Furthermore, inhibition of butyrylcholinesterase
      activity using 1 mM tetraisopropylpyrophosphoramide did not significantly affect
      triglyceride production or secretion. Human insulin (100 microU/ml) increased the
      production of butyrylcholinesterase without increasing triglyceride production.
      This demonstrates that stimulation of fatty acid production and
      butyrylcholinesterase activity occur by independent mechanisms and suggests that
      their correlation in hyperlipidemic conditions is not due to a direct
      relationship in production in situ.

PMID- 11577989
TI  - Potent induction of wild-type p53-dependent transcription in tumour cells by a
      synthetic inhibitor of cyclin-dependent kinases.
AB  - Activation of the p53 tumour suppressor protein by distinct forms of stress leads
      to inhibition of cellular proliferation by inducing cell cycle arrest or
      apoptosis. The cyclin-dependent kinase inhibitor roscovitine has been shown to
      induce nuclear accumulation of wild-type p53 in human untransformed and tumour
      derived cells. We analyzed the response of different human tumour cell lines to
      roscovitine treatment with respect to their p53 status. Striking induction of
      wild-type p53 protein and dramatic enhancement of p53-dependent transcription,
      coinciding with p21WAF1 induction, was observed in wildtype, but not mutant, p53
      bearing tumour cells after treatment with roscovitine. The transcriptional
      activity of p53 was substantially higher in roscovitine-treated cells than in
      cells irradiated with ultraviolet C or ionizing radiation, even though all these
      agents induced a similar amount of p53 accumulation. These results highlight the
      therapeutic potential of roscovitine as an anticancer drug, especially in tumours
      retaining a functional wild-type p53 pathway.

PMID- 11577990
TI  - Recombinant expression of perchloric acid-soluble protein reduces cell
      proliferation.
AB  - Perchloric acid-soluble protein (PSP) may play an important role in the
      regulation of cellular physiological functions because it has been highly
      conserved throughout evolution; however, this role has not been well elucidated.
      In previous reports, we suggested that PSP regulates cell proliferation. In this
      study, we examined the effect of PSP expression on proliferation of the normal
      rat kidney cell line NRK-52E, the rat hepatocyte cell line RLN-10, and the rat
      hepatoma cell line dRLh-84. Cells transfected with pcDNA-sense-PSP (pcDNA-S-PSP)
      over-expressed PSP mRNA and protein, and cell proliferation of the transfected
      cells was suppressed compared with that of cells transfected with pcDNA-empty
      (pcDNA-E). Cell viability of pcDNA-S-PSP-transfected cells was similar to that of
      pcDNA-E-transfected cells. Thus, over-expression of PSP suppresses cell
      proliferation without any influence on cell viability. These findings are the
      first to report an inhibitory activity of PSP on cell proliferation.

PMID- 11577991
TI  - Peroxisomes in the apocrine sweat glands of the human axilla and their putative
      role in pheromone production.
AB  - The products of the human apocrine axillary glands contain volatile steroids
      which act as pheromones. The steroidal structure of these pheromones implies that
      the axillary glands should be able to synthesize cholesterol which is the
      essential precursor of these molecules. Since important steps in cholesterol
      synthesis are localized within peroxisomes, we investigated the occurrence and
      the putative role of peroxisomes in the axillary glands at protein and mRNA
      levels by immunocytochemistry, Western blotting, and RT-PCR. Numerous peroxisomes
      were localized in the cells of the apocrine glands by immunocytochemistry, and
      the presence of catalase was confirmed by Western blotting and RT-PCR.
      Additionally, RT-PCR revealed the presence of mRNAs of two peroxisome-associated
      enzymes of the cholesterol biosynthetic pathway, mevalonate kinase and farnesyl
      diphosphate synthase. The results suggest that the peroxisomes in the human
      apocrine axillary glands may play a pivotal role in the biosynthesis of
      pheromones.

PMID- 11577992
TI  - Arginase expression in peritoneal macrophages and increase in circulating
      polyamine levels in mice infected with Schistosoma mansoni.
AB  - We investigated the nitric oxide (NO) synthase and arginase pathways in resident
      peritoneal macrophages of mice infected with the tropical parasite Schistosoma
      mansoni. The two enzymes may have opposite effects, insofar as NO may be involved
      in the killing of the parasite whereas arginase may stimulate parasite growth via
      polyamine synthesis. We determined the effects of the infection on the expression
      and activity of the two enzymes in macrophages, before and after cytokine
      activation. Cells from infected mice expressed the hepatic type I arginase,
      whereas in control cells, the enzyme was expressed only after cytokine
      activation, as were NO synthase II and type II arginase in both groups of cells.
      Moreover, we found that in infected mice, arginase expression in macrophages was
      associated with a ten fold increase in the concentration of circulating ornithine
      derived polyamines. This may be of pathological importance, since parasitic
      helminths are though to be dependent on their hosts for the uptake and
      interconversion of polyamines.

PMID- 11577993
TI  - Effects after inhalation of (1-->3)-beta-D-glucan in healthy humans.
AB  - BACKGROUND AND AIM: This study was performed to assess the effects of an exposure
      to a pure (1-->3)-beta-D-glucan, a cell wall component of fungi, plants and
      certain bacteria. METHODS: Twenty-one healthy subjects inhaled saline or (1-->3)
      beta-D-glucan suspended in saline in a random, double-blind, cross-over design.
      They were examined before exposure and 24 and 72h afterwards with spirometry,
      blood sampling and collection of induced sputum. Differential cell counts and
      eosinophilic cationic protein (ECP) were determined in blood and sputum, and
      myeloperoxidase (MPO), tumour necrosis factor-alpha (TNF-alpha), and interleukin
      (IL)-8 and IL-10 were determined in sputum supernatants. TNF-alpha was determined
      after cultivation of blood mononuclear cells. RESULTS: In sputum, inhalation of
      saline caused a significant increase in ECP and TNF-alpha. (1-->3)-beta-D-Glucan
      inhalation caused a further increase in these cytokines, although not
      statistically significantly different from the increase induced by inhalation of
      saline alone. In blood, the number of eosinophils was significantly decreased 72
      h after the challenge with (1-->3)-beta-D-glucan. This effect was not found after
      the inhalation of saline alone. TNF-alpha production from stimulated blood
      mononuclear cells was significantly decreased 72 h after the (1-->3)-beta-D
      glucan inhalation as compared with the increase induced by saline inhalation.
      CONCLUSIONS: The results suggest that (1-->3)-beta-D-glucan causes a different
      type of response as compared with inflammatory agents such as bacterial endotoxin
      that cause a neutrophil-dominated inflammatory response.

PMID- 11577994
TI  - Lymphocyctes Tgammadelta in clinically normal skin and peripheral blood of
      patients with systemic lupus erythematosus and their correlation with disease
      activity.
AB  - Human Tgammadelta lymphocytes constitute from 1 to 15% of all peripheral blood
      lymphocytes. Recent work has demonstrated that this population plays a major role
      in the pathogenesis of infectious and immune diseases. Increased numbers of
      gammadelta T cells have been found in affected skin from systemic sclerosis and
      chronic cutaneous lupus erythematosus patients. In our study, we have determined
      the numbers of Tgammadelta lymphocytes and their subpopulations in peripheral
      blood from 29 patients with systemic lupus erythematosus (SLE) and in 19 healthy
      volunteers using flow cytometry and specific monoclonal antibodies. The same
      cells in uninvolved skin from SLE patients and human controls using
      immunohistochemical analysis were estimated. T-Cell receptor (TCR) delta chain
      gene rearrangement was identified with primers for Vdelta1, Vdelta2 and Vdelta3
      by the polymerase chain reaction. Statistical analysis showed a significantly
      decreased number of gammadelta T cells in SLE patients (26.4+/-16.9/microl)
      compared with the control group (55.3+/-20.6/microl (p < 0.001). The number of
      Vdelta2 TCR+ and Vgamma9 TCR+ subpopulations was also lower in SLE patients than
      in healthy persons. No statistical correlation between disease activity and the
      number of gammadelta T cells was demonstrated. The percentage of Tgammadelta
      lymphocytes in clinically normal skin from SLE patients was twice (22.0+/-9.4%)
      that found in the skin from healthy persons (11.1+/-5.5%) (p < 0.002). Higher
      percentages of the Vdelta2 TCR+ and Vgamma9 TCR+ subpopulation of lymphocytes
      were found in the skin from SLE patients. We have also found positive correlation
      between the percentage of Tgammadelta lymphocytes in skin and the activity of SLE
      (r=0.594, p < 0.001), and between subpopulation Vdelta3 TCR+ and disease activity
      (r=0.659, p< 0.001). In conclusion, the results of our studies demonstrate that,
      in patients with SLE, accumulation of Tgammadelta lymphocytes can be seen in
      clinically normal skin, and the percentage of these cells correlates with the
      activity of the disease.

PMID- 11577996
TI  - Establishment of a consistent L929 bioassay system for TNF-alpha quantitation to
      evaluate the effect of lipopolysaccharide, phytomitogens and cytodifferentiation
      agents on cytotoxicity of TNF-alpha secreted by adherent human mononuclear cells.
AB  - TUMOR necrosis factor-alpha (TNF-alpha) plays an important role in the
      pathogenesis of rheumatoid arthritis. The present study was to evaluate the
      effects of lipopolysaccharide (LPS), phytomitogens and cytodifferentiation agents
      on cytotoxicity of TNF-alpha secreted by adherent human mononuclear cells (AMC).
      TNF-alpha cytotoxicity in LPS-treated, phytomitogen-treated, and
      cytodifferentiation agent-treated AMC supernatants were analyzed by the L929
      bioassay system. Our results showed that LPS could induce homogeneous TNF-alpha
      production by AMC whereas, in addition to TNF-alpha, phytomitogens could also
      induce other TNF-like factors. Neither methotrexate, retinoic acid nor sodium
      butyrate can inhibit TNF-alpha cytotoxicity, while hexamethylene bisacetamide
      could not only inhibit TNF-alpha cytotoxicity but also TNF-alpha inducing ability
      of LPS to AMC.

PMID- 11577995
TI  - Tumor necrosis factor-alpha/interleukin-10 balance in normal and cystic fibrosis
      children.
AB  - BACKGROUND: The balance between tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-10 (IL-10) is important for immune homeostasis maintenance. Exuberant
      production of TNF-alpha contributes to overwhelming inflammatory response and
      tissue damage. But, commonly, increase in TNF-alpha is counterbalanced by
      simultaneous synthesis of an anti-inflammatory cytokine IL-10, which suppresses
      production of many activating and regulatory mediators. AIMS: In the present
      study, the relationships between TNF-alpha and IL-10 in the plasma of healthy
      school-children and cystic fibrosis (CF) patients have been investigated.
      METHODS: Blood samples were obtained from 12 CF patients with chronic pulmonary
      disease and 18 healthy schoolchildren vaccinated with live attenuated rubella
      vaccine. IL-10 and TNF-alpha were determined in the plasma samples using
      commercially available enzyme-linked immunosorbent assay kits. RESULTS: Before
      vaccination, most healthy children (13 of 18) demonstrated superiority of pro
      inflammatory TNF-alpha over anti-inflammatory IL-10 (TNF-alpha/IL-10 > 1). In
      these subjects, a significant positive linear association between the cytokine
      values has been found. Vaccine challenge resulted in a marked reduction of TNF
      alpha/IL-10 ratios. In addition, a disappearance of correlation between the
      cytokine values was observed. Such disturbance was related to exuberant elevation
      of the IL-10 levels after inoculation. On the contrary, in CF individuals, plasma
      cytokine values remained in strong linear association independently of TNF-alpha
      or IL-10 predominance. No spikes in the plasma levels of IL-10 in CF patients
      during a 6-month observation period have been revealed. CONCLUSIONS: There were
      no fundamental differences between CF and healthy children in the regulation of
      TNF-alpha and IL-10 secretion. Thus, immune quiescence seemed to be associated
      with the predominance of TNF-alpha, whereas immune disturbance was characterized
      by IL-10 superiority. The only abnormality that was found in CF patients
      consisted of their inability to produce unlimitedly IL-10 in response to antigen
      stimuli.

PMID- 11577997
TI  - Diphenyleneiodonium inhibits NF-kappaB activation and iNOS expression induced by
      IL-1beta: involvement of reactive oxygen species.
AB  - AIMS: In this work, we studied the mechanisms by which diphenyleneiodonium
      chloride (DPI) inhibits nitric oxide (NO) synthesis induced by the
      proinflammatory cytokine interleukin-1beta (IL-1) in bovine articular
      chondrocytes. To achieve this, we evaluated the ability of DPI to inhibit the
      expression and activity of the inducible isoform of the NO synthase (iNOS)
      induced by IL-1. We also studied the ability of DPI to prevent IL-1-induced NF
      kappaB activation and reactive oxygen species (ROS) production. RESULTS: Northern
      and Western blot analysis, respectively, showed that DPI dose-dependently
      inhibited IL-1-induced iNOS mRNA and protein synthesis in primary cultures of
      bovine articular chondrocytes. DPI effectively inhibited NO production
      (IC50=0.03+/-0.004 microM), as evaluated by the method of Griess. Nuclear factor
      kappa B (NF-kappaB) activation, as evaluated by electrophoretic mobility shift
      assay, was inhibited by DPI (1-10 microM) in a dose-dependent manner. IL-1
      induced ROS production, as evaluated by measurement of dichlorofluorescein
      fluorescence, was inhibited by DPI at concentrations that also prevented NF
      kappaB activation and iNOS expression. CONCLUSIONS: DPI inhibits IL-1-induced NO
      production in chondrocytes by two distinct mechanisms: (i) by inhibiting NOS
      activity, and (ii) by preventing iNOS expression through the blockade of NF
      kappaB activation. These results also support the involvement of reactive oxygen
      species in IL-1-induced NF-kappaB activation and expression of NF-kappaB
      dependent genes, such as iNOS.

PMID- 11577998
TI  - Analysis of IgE turnover in non-sensitized and sensitized rats.
AB  - BACKGROUND: Although the levels of immunoglobulin E (IgE) in the circulating
      blood are often elevated in patients with allergic diseases, such levels cannot
      always be considered as pathognomonic signs of allergy. The induction of allergic
      reactions in the tissue was inferred to be related to the amount of IgE passing
      through the vascular wall. AIMS: We attempted to clarify which compartment, the
      intravascular or extravascular, plays an important role in the regulation of the
      turnover of rat IgE. METHODS: The level of DNP-specific rat IgE in the serum was
      estimated by IgE-capture enzyme-linked immunosorbent assay, and the turnover of
      IgE was analyzed from its pharmacokinetic parameters. RESULTS: The transfer rate
      constants from the central to tissue compartment (Kct) were larger than those
      from the tissue to central compartment (Ktc) irrespective of the sensitized
      state. The value of the distribution volume of the tissue compartment (Vt) was
      larger than that of the distribution volume of the central compartment (Vc)
      irrespective of the sensitized state. CONCLUSIONS: These Findings suggest that
      the short half-life of rat IgE in the circulation could be attributable to the
      distribution of IgE from the intravascular to the extravascular compartment.

PMID- 11577999
TI  - Myeloperoxidase and adenosine-deaminase levels in the pleural fluid leakage
      induced by carrageenan in the mouse model of pleurisy.
AB  - BACKGROUND: Although myeloperoxidase (MPO) and adenosine-deaminase (ADA) levels
      are markers of activated leukocytes, both enzymes have not been currently
      addressed in inflammation models. AIMS: This study evaluates whether the
      concentrations of these enzymes are significantly correlated with the content of
      leukocytes in a pleurisy model. METHODS: The pleurisy was induced by carrageenan
      (1%) in mice, and the parameters analyzed 4 and 48 h after. RESULTS: After the
      induction of inflammation (4h), MPO and ADA levels peaked in parallel to
      neutrophils (p<0.01). Regarding the second phase of pleurisy (48 h), the highest
      concentrations of ADA were detected in parallel to the highest levels of
      mononuclears (p<0.01). At this time, MPO levels and neutrophils remained
      elevated, although at lower levels than those found at 4 h. A significant
      positive correlation was found among neutrophiLs and MPO, and mononuclears and
      ADA (p<0.01). CONCLUSIONS: These findings support the evidence that both enzymes
      are markers of the inflammatory process, and provide new tools for a better
      understanding of the immunoregulatory pathways that occur in inflammation.

PMID- 11578001
TI  - The material and the symbolic in theorizing social stratification: issues of
      gender, ethnicity and class.
AB  - Within most approaches to stratification gender and ethnicity are seen to pertain
      primarily to the symbolic or cultural realms, whilst class is regarded as
      pertaining to material inequality. This constructs gender and ethnic positioning
      as entailing honour, deference, worth, value and differential treatment
      (sometimes expressed through the notion of 'status'), but the social relations
      around these are themselves not seen as constitutive of social stratification. In
      this paper I will rethink social stratification away from the polarity between
      the material and the symbolic, and argue that material inequality, as a set of
      outcomes relating to life conditions, life chances and solidary processes, is
      informed by claims and struggles over resources of different types, undertaken in
      terms of gender, ethnicity/race and class. This formulation allows us to include
      these categorial formations, alongside class, as important elements of social
      stratification i.e. as determining the allocation of socially valued resources
      and social places/locations.

PMID- 11578000
TI  - Evidence that behavioral depression does not influence airway cell influx in
      allergic rats.
AB  - This study was designated to evaluate the influence of behavioral depression on
      the airway leukocyte recruitment in allergic animals. To achieve this, total and
      differential cell counts in bronchoalveolar (BAL) fluid of ovalbumin (OVA)
      sensitized and depressed rats was evaluated. Inescapable electric footshock,
      applied on day 0, 7 and 13 after OVA sensitization, was used as a model to induce
      depression. In both nondepressed and depressed groups, the number of total and
      differential cells (eosinophils and mononuclear cells) in BAL fluid was
      significantly larger in sensitized compared with non-sensitized animals. However,
      no statistical differences were found between these groups with respect to the
      number of total and differential leukocytes, irrespective of the day inescapable
      shock was applied. Thus, behavioral depression does not influence the pattern of
      cell infiltration into the airways of allergen-induced airway inflammation.

PMID- 11578002
TI  - Women and class structure in contemporary Japan.
AB  - The main purpose of this study is to examine how to determine the class position
      of women, especially married women, in Japan. This study examines three different
      approaches to conceptualizing women's position in the class structure: the
      conventional approach, the individual approach, and the dominance approach. Since
      1975, the overall rate of female labour force participation in Japan has
      increased, and given this growth, particularly of employees working outside home,
      I discuss whether the increased entry of women, particularly married women, into
      the labour market challenges the conventional way of assigning class positions to
      women by simply deriving them from their husband's class positions. The data set
      used in this study is derived from the 1995 Japanese Social Stratification and
      Mobility Survey. An examination of class distributions suggests that the pictures
      of macro-class structure provided by the conventional approach and the dominance
      approach show very little difference. Married women who belong to the female
      dominant family still form a very small minority of all married women in the
      society. Furthermore, the male-dominant family shows the greatest stability over
      the life course whereas the female-dominant family, where the wife experiences
      withdrawal from the labour market, is least stable. The increasing number of
      married women in the labour market, thus, has not yet become a major threat to
      the conventional way of assigning women to a class position in contemporary
      Japan. Women, even among those working on a full-time basis, perceive their
      position in the stratification system using not only their own work, but also
      their husband's. In contrast, men's perception is determined by their own
      education and employment, not by their wives'. This asymmetry in the effect of
      the husband's class and of the wife's class on class identification is related
      not only to gender inequality within the labour market but also to the division
      of labour by gender within the household.

PMID- 11578003
TI  - Class structure in a deeply divided society: class and ethnic inequality in
      Israel, 1974-1991.
AB  - Despite the fact that in many societies ethnicity plays an important role in
      stratification processes, a common view held by students of stratification argues
      that the role of ascriptive criteria in stratification processes is diminishing,
      and that the main axis of the modern stratification system is rooted in the
      division of labour in the marketplace. Despite this, most Israeli sociologists
      have taken the ethnic and national cleavages to be the main axes of
      stratification in Israel. This paper utilizes the 1974 and 1991 mobility surveys
      in Israel to examine changes over time in the association between
      ethnicity/nationality (i.e., Ashkenazi-Jews, Sephardi-Jews and Israeli-Arabs) and
      class position in the Israeli stratification structure. It also examines the
      extent to which inequality of opportunity within the Israeli class structure is
      affected by ethnicity/nationality. Here it is found that the ethnic/national
      cleavage in Israel appears to have played a less important role over time in the
      allocation of Israeli men to class positions. It is shown that class
      crystallization processes that result from the differentiation of employment
      contracts in the marketplace produce a relatively common level of inequality of
      opportunity in Israel, across sub-populations and over time. Any difference in
      the level of inequality of opportunity between the various sub-populations would
      appear to result, in part, from different historical process of, and government
      policy towards, the three sub-populations.

PMID- 11578004
TI  - Testing the modernization hypothesis and the socialist ideology hypothesis: a
      comparative sibling analysis of educational attainment and occupational status.
AB  - In this study, we present a comparative sibling analysis. This enables us to test
      two major social mobility hypotheses, i.e. the modernization hypothesis and the
      socialist ideology hypothesis. We employ survey data on brothers in England,
      Hungary, the Netherlands, Scotland, Spain, and the USA, covering a historical
      period from 1916 till 1990. Results show that the effects of parental social
      class on educational attainment are smaller in technologically advanced
      societies, and that the effects of parental social class on occupational status
      are smaller in social-democratic and communist societies. In addition, the total
      family impact on occupational status declines with modernization. But overall, we
      observe that the family of origin has not lost its importance for its sons'
      educational attainment and occupational status yet.

PMID- 11578005
TI  - Modernization, globalization and the welfare state: a comparative analysis of old
      and new convergence of social insurance since 1930.
AB  - Convergence of policies and institutions across countries has been a recurrent
      theme within social sciences. 'Old' and 'new' convergence hypotheses have been
      associated with changing concepts and catchwords, such as modernization, logic of
      industrialism, post-industrialism, post-Fordism and globalization, but share some
      underlying theoretical perspectives. The purpose of this paper is to analyse
      tendencies towards convergence of social insurance systems in 18 OECD countries
      between 1930 and 1990, a period which has seen our sample of countries develop
      from predominantly agricultural societies to industrial or post-industrial market
      democracies. Data from the Social Citizenship Indicator Program (SCIP) are used
      to examine the development of institutional variables within the various national
      social insurance systems. Sub-samples of larger and smaller countries are
      examined separately, in order to test the open-economy hypothesis that smaller
      countries, being more exposed to international pressures than larger ones, could
      be expected to show higher degrees of social protection and also more
      convergence. Hypotheses on differentiated institutional barriers against
      pressures from the processes of transnationalization of the economy, as well as
      possible convergence effects of the supra-national policy making within the
      European Union, are discussed in the last section.

PMID- 11578006
TI  - Childhood poverty, early motherhood and adult social exclusion.
AB  - Childhood poverty and early parenthood are both high on the current political
      agenda. The key new issue that this research addresses is the relative importance
      of childhood poverty and of early motherhood as correlates of outcomes later in
      life. How far are the 'effects' of early motherhood on later outcomes due to
      childhood precursors, especially experience of childhood poverty? Subsidiary
      questions relate to the magnitude of these associations, the particular levels of
      childhood poverty that prove most critical, and whether, as often assumed, only
      teenage mothers are subsequently disadvantaged, or are those who have their first
      birth in their early twenties similarly disadvantaged? The source of data for
      this study is the National Child Development Study. We examine outcomes at age 33
      for several domains of adult social exclusion: welfare, socio-economic, physical
      health, emotional well-being and demographic behaviour. We control for a wide
      range of childhood factors: poverty; social class of origin and of father;
      mother's and father's school leaving age; family structure; housing tenure;
      mother's and father's interest in education; personality attributes; performance
      on educational tests; and contact with the police by age 16. There are clear
      associations for the adult outcomes with age at first birth, even after
      controlling for childhood poverty and the other childhood background factors.
      Moreover, we demonstrate that the widest gulf in adult outcomes occurs for those
      who enter motherhood early (before age 23), though further reinforced by teenage
      motherhood for most adult outcomes. We also show that any experience of childhood
      poverty is clearly associated with adverse outcomes in adulthood, with
      reinforcement for higher levels of childhood poverty for a few outcomes.

PMID- 11578007
TI  - Pension prospects of minority ethnic groups: inequalities by gender and
      ethnicity.
AB  - Minority ethnic groups have low income in later life from private pensions,
      partly due to shorter employment records in Britain since migration. Yet
      disadvantage and discrimination in the labour market, as well as differences in
      cultural norms concerning women's employment, may lead to persistence of ethnic
      variation in private pension acquisition. Little is known about the pension
      arrangements made by men and women in minority ethnic groups during the working
      life. This paper examines the extent of ethnic disadvantage in private pension
      scheme arrangements and analyses variation according to gender and specific
      ethnic group, using three years of the British Family Resources Survey, which
      provides information on over 97,000 adults aged 20-59, including over 5,700 from
      ethnic minorities. Both men and women in minority ethnic groups were less likely
      to have private pension coverage than their white counterparts but the extent of
      the difference was most marked for Pakistanis and Bangladeshis. Ethnicity
      interacted with gender, so that Blacks showed the least gender inequality in
      private pension arrangements, reflecting the relatively similar full-time
      employment rates of Black men and women. A minority ethnic disadvantage in
      private pension coverage, for both men and women, remained after taking account
      of age, marital and parental status, years of education, employment variables,
      class and income. The research suggests that minority ethnic groups - especially
      women - will be disproportionately dependent on means-tested benefits in later
      life, due to the combined effects of low private pension coverage and the policy
      of shifting pension provision towards the private sector.

PMID- 11578008
TI  - A rejoinder to Abell and Reyniers' 'failure of social theory'.

PMID- 11578009
TI  - Rheumatic diseases and malignancy--is there an association?
AB  - An association between rheumatic diseases and malignancy has been claimed in a
      variety of settings. This editorial reviews published data addressing the overall
      risk of malignancy, and of particular types of cancer, in the context of various
      autoimmune rheumatic diseases. For patients with Sjogren's syndrome, systemic
      sclerosis with pulmonary fibrosis, or with dermatomyositis/polymyositis there is
      a documented association with an increased risk of malignant disease. Patients
      with rheumatoid arthritis may also have an increased risk of cancer. It is still
      controversial whether systemic lupus erythematosus is associated with an
      increased risk of developing malignancy. More epidemiologic studies are needed to
      try and clarify many of these associations, in particular the potential risks
      associated with cytotoxic therapy.

PMID- 11578010
TI  - D-penicillamine is not an effective treatment in systemic sclerosis.
AB  - Based on open studies. D-penicillamine (DPA) has been used for the treatment of
      systemic sclerosis (SSc) but we believe the controlled trial of this drug in SSc
      does not support its use to treat this disease. Open trials are inevitably biased
      by selection bias and randomized, blinded, controlled studies are required to
      minimize both known and unknown confounding variables. The high vs. low dose DPA
      trial was a well-controlled, randomized, double-blind study which met criteria
      for a high quality study, although it was not placebo-controlled. Toxicity was
      increased in the high dose group, thus showing a biologic response, although the
      study showed no clinical efficacy differences between a mean dose of 120mg DPA
      every other day (equivalent to 60mg qd) and a mean dose of 822mg DPA daily. One
      might argue that 60mg DPA is effective, but we believe this is highly unlikely,
      as doses significantly higher than this have been shown to be ineffective in
      other connective tissue diseases such as rheumatoid arthritis. In our opinion. D
      penicillamine is, unfortunately, ineffective in treating early, diffuse, systemic
      sclerosis.

PMID- 11578011
TI  - D-penicillamine in systemic sclerosis? Yes!
AB  - The use of D-penicillamine in systemic sclerosis (SSc) has been controversial. We
      have reviewed the major published studies on this drug in SSc with diffuse
      cutaneous (dc) involvement and summarized our own recent experience in dcSSc
      patients treated with and without D-penicillamine. We conclude that D
      penicillamine favourably alters the natural history of skin involvement in dcSSc,
      even when used in low dose. Furthermore, recurrence of diffuse skin change after
      discontinuation of D-penicillamine and improvement in skin thickening after
      reinitiation of the drug support its effectiveness. We believe that the
      rheumatologic community should use D-penicillamine in patients with early dcSSc.

PMID- 11578012
TI  - Survival study of rheumatoid arthritis patients in Madrid (Spain). A 9-year
      prospective follow-up.
AB  - OBJECTIVE: To determine the risk and causes of death in rheumatoid arthritis (RA)
      patients in Madrid. METHODS: A longitudinal survival analysis was made. 182 RA
      patients of the rheumatology clinic of a tertiary care hospital were studied. 42
      (23%) males and 140 (77%) females. All were followed-up for a 9-year period or to
      the date of death. Kaplan-Meier survival curves for both male and female cohorts
      were performed. The logrank test was used to compare both distributions and to
      determine the statistical significance. RESULTS: The mortality rate for the RA
      patient cohort was 15.4 deaths/1000 person-years (10.2/1000 for the female and
      34.2/1000 for the male cohorts). The mortality rate ratio was 3.3. The logrank
      test showed a statistical difference (p=0.0023). The standardized mortality ratio
      was 1.85 for RA patients. The causes of death were: cardiovascular diseases 5
      (21%), infections 5 (21%). amyloidosis 4 (17%), malignant diseases 2 (8%).
      CONCLUSIONS: Mortality is nearly two times higher in our population of RA
      patients. Male patients have a much lower survival probability than females.
      Cardiovascular diseases, infections and amyloidosis were the most common causes
      of death.

PMID- 11578013
TI  - Changes in therapy of rheumatoid arthritis during the period 1979 to 1996.
AB  - OBJECTIVE: To evaluate the use of disease modifying antirheumatic drugs (DMARDs),
      cytotoxic agents, and corticosteroid therapy in patients diagnosed with
      rheumatoid arthritis (RA) in two periods, 1979 to 1987, and 1988 to 1996.
      MATERIALS AND METHODS: Review of the records of 788 patients with RA diagnosed at
      the Department of Rheumatology, the University Hospital of Tromso. RESULTS: We
      found a significant increase in the proportion of patients who started with
      auranofin, sulfasalazine, methotrexate, and corticosteroids in 1988 1996 compared
      to 1979 1987. The initiation of use of gold salts, antimalarials, and D
      penicillamine declined significantly from the first to the second period.
      CONCLUSION: Patients diagnosed with RA between 1988-1996 were treated more
      actively than patients diagnosed in the period 1979-1987. During 1988 to 1996
      auranofin, sulphasalazine, methotrexate, and corticosteroids replaced gold salts,
      antimalarials, and D-penicillamine.

PMID- 11578014
TI  - Randomized, double-blind trial of anti-interferon-gamma antibodies in rheumatoid
      arthritis.
AB  - INTRODUCTION: An increasing body of evidence indicates that interferon (IFN )
      gamma is an immunoregulator and may play a key role in the pathogenesis of
      autoimmune diseases, including rheumatoid arthritis (RA). OBJECTIVE: To assess
      the efficacy and tolerability of anti-IFN-gamma in patients with active RA.
      METHODS: In a randomized, double-blind trial, 30 patients with active RA were
      randomly assigned to receive intramuscular injections of anti-IFN-gamma, anti-TNF
      alpha, or placebo for 5 consecutive days. RESULTS: Both anti-cytokines were
      significantly superior to placebo. Patients stopping treatment due to lack of
      efficacy included I receiving anti-TNF-alpha, 2 receiving anti-IFN-gamma, and 9
      receiving placebo. According to the physician's assessment, improvement was
      achieved by the 7th day in 9 patients receiving anti-TNF-alpha, 7 receiving anti
      IFN-gamma, and 2 receiving placebo. By day 28 the corresponding figures were 8,
      8, and 0, respectively. CONCLUSION: Antibodies to IFN-gamma could be a promising
      approach to treating RA, especially its treatment-resistant forms.

PMID- 11578015
TI  - Selenium supplementation in rheumatoid arthritis investigated in a double blind,
      placebo-controlled trial.
AB  - INTRODUCTION: Selenium is an essential trace element with antioxidant properties.
      Trials with selenium have been conducted in rheumatoid arthritis (RA) to correct
      impaired selenium status and increase defences against deleterious oxidant
      species. AIM OF THE STUDY: To investigate in a double blind multi-centric placebo
      controlled study the effects of selenium supplementation in RA. METHODS: Fifty
      five patients with moderate RA received during 90 days either capsules containing
      selenium-enriched yeast (200 microg/d) or a placebo. RESULTS: The visual analog
      scale, the Ritchie index, the number of swollen and painful joints, and morning
      stiffness significantly decreased with time in both groups (p<0.001), but no
      difference between groups could be identified. When examining the quality of life
      a significant (p<0.01) improvement in arm movements and health feeling was
      evidenced in selenium-treated patients. CONCLUSION: Selenium treatment did not
      show clinical benefit on RA. Interestingly, the improval in both groups
      demonstrated a placebo effect of the intervention trial.

PMID- 11578016
TI  - Bone mineral density in women and men with early rheumatoid arthritis.
AB  - OBJECTIVE: To study bone mineral density (BMD) in patients with early rheumatoid
      arthritis. METHODS: Dual x-ray absorptiometry was performed in 227 patients, 149
      women and 78 men, with rheumatoid arthritis (RA) of no more than 12 months
      duration. RESULTS: Women, as well as men above 60 years of age, had a BMD at
      spine and hip comparable with age and sex matched reference populations. Men
      younger than 60 years had a tendency to lower BMD. Although the proportion of
      female patients with osteoporosis was not higher than in the reference,
      population the proportion of patients with reduced bone mass was increased, and
      this was found also in men. There was no significant association between BMD and
      disease duration, disease activity or disability. CONCLUSION: Untreated patients
      with early RA have a BMD in spine and hip not significantly different from that
      of normal reference populations. However, an increased number of the patients had
      reduced bone mass already at disease onset.

PMID- 11578017
TI  - Antifilaggrin antibodies in early rheumatoid arthritis may predict radiological
      progression.
AB  - OBJECTIVE: To elucidate the possibility that autoantibodies to filaggrin,
      detected in patients with early RA (having a disease duration of not more than
      one year), may predict joint destruction assessed after five years of
      observation. METHODS: This is a 5 yr extension of a previous study (1) of 112
      consecutive patients with early RA. Serum antifilaggrin autoantibodies were
      detected by immunoblotting (AFA) and by indirect immunofluorescence ("AKA").
      DAS28, pain on a VAS. HAQ, and CRP were measured. Plain X-ray films were taken
      from hands and forefeet and a Larsen score was calculated. RESULTS: Ninety-two of
      the original 112 patients had baseline X-rays available and constituted the study
      material. At 5 year follow-up, 67 of these 92 have been assessed and for 63 of
      these X-rays were available. For the whole patient material, significant
      radiological progression, measured by Larsen scores, occurred while disease
      activity and function (pain VAS, DAS28, CRP, and HAQ) improved significantly over
      five years. The groups of patients having AFA or "AKA" at baseline had
      significantly (p=0.006 and p<0.001, respectively) higher Larsen scores five years
      later than the groups without these antibodies. No clear relation of these
      antibodies to disease activity or function was demonstrated, except that the
      group of patients with "AKA" had significantly higher median CRP (p=0,003) after
      five years. CONCLUSIONS: The present study shows that antifilaggrin
      autoantibodies may predict radiological progression. The prognostic value of
      these antibodies will be further evaluated in relation to other potential markers
      in a larger patient material.

PMID- 11578018
TI  - Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in
      rheumatoid arthritis.
AB  - The purpose of this study was to evaluate if IL-1beta (IL-1beta promoter and IL
      1beta exon 5) and IL-1receptor antagonist (IL-1Ra) gene polymorphisms act as
      markers of susceptibility to or severity of RA. The study included 104 RA
      patients and 103 normal controls. No significant difference was observed in the
      cytokine allelic frequencies of IL-1beta promoter and IL-1beta exon 5 between
      patients with RA and healthy controls. In addition, there was no significant
      association in the cytokine carriage rates of I and II allele of IL-1Ra between
      RA patients and healthy controls. In contrast, the IV allele of IL-1Ra was
      significantly increased in RA patients with low inflammatory activity (P=0.03).
      This study indicated that allelic frequency and carriage rate of IL-1beta (IL
      1beta promoter and IL-1beta exon 5) and IL-1Ra (I and II allele) do not differ
      significantly between normal controls and RA patients in Taiwan. However, the
      carriage rate of IV allele of IL-1Ra was high in the RA patients with low
      inflammatory activity.

PMID- 11578019
TI  - Elevated levels of osteoprotegerin (OPG) and hepatocyte growth factor (HGF) in
      rheumatoid arthritis.
AB  - Rheumatic diseases are often associated with changes in bone metabolism.
      Excessive production and release of cytokines and other growth factors due to
      inflammation, e.g. tumor necrosis factor-alpha (TNF-alpha), receptor activator of
      NF-kappaB ligand (RANKL), interleukins such as IL-1 and IL-6, may cause
      alterations in bone homeostasis leading to bone degradation. Other components
      such as osteoprotegerin (OPG) and possibly the ligand-receptor pair hepatocyte
      growth factor (HGF) and c-met may counteract this destruction, we have measured
      the levels of OPG, and HGF c-met, in serum, synovial fluid (SF), and cartilage
      from patients with rheumatoid arthritis (RA) and other arthritides. We found a)
      elevated levels of both OPG and HGF in SF from RA patients relative to
      arthritides of other causes, b) increased levels of both OPG and HGF in SF from
      seropositive RA patients (RA+) compared to seronegative RA patients (RA-), c)
      elevated levels or both OPG and HGF in serum from RA patients compared to healthy
      controls, d) no correlation between severity of inflammation and levels of OPG or
      HGF, and e) presence of HGF c-met in both cartilage and synovial tissue. The most
      significant elevations of OPG and HGF were found in patients with RA, the
      rheumatic disease most frequently associated with the development of secondary
      osteoporosis.

PMID- 11578020
TI  - Antiphosphatidylethanolamine antibodies contribute to the diagnosis of
      antiphospholipid syndrome in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the correlation between antiphosphatidylethanolamine
      antibodies (aPE) and some antiphospholipid antibodies (aPL)-related clinical
      manifestations in patients with systemic lupus erythematosus (SLE). METHODS:
      Patients with SLE (n=217) were tested for the presence of aPE, anticardiolipin
      antibodies (aCL), and lupus anticoagulant (LA). The prospective aPL-related
      clinical manifestations studied were: thrombosis, thrombocytopenia, recurrent
      fetal losses, heart valvulopathies, hemolytic anemia, livedo reticularis, and
      pulmonary hypertension. RESULTS: A total of 109 SLE patients (50.23%) were IgG
      aPE-positive; 17.51% presented aPE as the sole autoantibody and had some clinical
      features of aPL-related clinical manifestations. IgG aPE were associated to the
      presence of heart valvulopathies (p=0.002). A statistical difference was also
      found when considering high levels of IgG aPE (O.D.>0.600) in patients with
      livedo reticularis (p=0.008). CONCLUSION: The evaluation of IgG aPE may allow us
      to detect some more patients with aPL-related clinical manifestations in the SLE
      population, aPE correlated particularly with valvulopathies and livedo
      reticularis.

PMID- 11578021
TI  - Symptoms modifying effect of avocado/soybean unsaponifiables (ASU) in knee
      osteoarthritis. A double blind, prospective, placebo-controlled study.
AB  - OBJECTIVES: We compare the symptomatic effects of 300 or 600mg daily of ASU in
      patients with knee osteoarthritis. METHODS: A multicenter, double blind, study
      comparing a daily intake of 300mg or 600mg of ASU and placebo. The study lasted 3
      months and involved patients of both genders, aged 45 to 80 years and presenting
      with femoro-tibial knee osteoarthritis. The primary endpoint was NSAIDs and
      analgesics intake between D30 and D90. RESULTS: All efficacy parameters were
      significantly improved (p<0.01), in the two ASU groups compared to the placebo
      group. At D90, NSAIDs and analgesics intake decreased by more than 50% in 71% of
      the patients receiving ASU 300mg or 600mg, compared to 36% of the patients
      receiving placebo. From DO to D90 Lequesne's index dropped by 3.9 and 2.9 points
      in ASU 300mg and 600mg groups, respectively, against 1.6 in those receiving
      placebo. CONCLUSION: The efficacy of ASU at a dosage of 300mg/day and 600mg/day
      was consistently superior to that of placebo at all endpoints, with no
      differences observed between the two doses.

PMID- 11578022
TI  - Concussion in sports: minimizing the risk for complications.
AB  - Mild traumatic brain injury, or concussion, is a common consequence of
      collisions, falls and other forms of contact in sports. Concussion may be defined
      as an acute trauma-induced alteration of mental function lasting fewer than 24
      hours, with or without preceding loss of consciousness. The physician's
      responsibilities in assessing an athlete with concussion include determining the
      need for emergency intervention and offering guidance about the athlete's ability
      to return to play. Concussion may be complicated by cerebral edema related to the
      second impact syndrome, cumulative neuropsychologic deficits, intracranial
      bleeding or the postconcussion syndrome. The risk of complications is increased
      in athletes who prematurely return to play and in those with prolonged loss of
      consciousness or post-traumatic amnesia. An athlete with prolonged loss of
      consciousness or signs and symptoms that worsen or persist after a concussion
      should be evaluated in the emergency department. An athlete should not be allowed
      to resume sports participation until all symptoms of a concussion have resolved.

PMID- 11578023
TI  - Management of common symptoms in terminally ill patients: Part II. Constipation,
      delirium and dyspnea.
AB  - In addition to pain, patients who are approaching the end of life commonly have
      other symptoms. Unless contraindicated, prophylaxis with a gastrointestinal
      motility stimulant laxative and a stool softener is appropriate in terminally ill
      patients who are being given opioids. Patients with low performance status are
      not candidates for surgical treatment of bowel obstruction. Cramping abdominal
      pain associated with mechanical bowel obstruction often can be managed with
      morphine (titrating the dosage for pain) and octreotide. Delirium is common at
      the end of life and is frequently caused by a combination of medications,
      dehydration, infections or hypoxia. Haloperidol is the pharmaceutical agent of
      choice for the management of delirium. Dyspnea, the subjective sensation of
      uncomfortable breathing, is often treated by titration of an opioid to relieve
      the symptom; a benzodiazepine is used when anxiety is a component of the
      breathlessness.

PMID- 11578024
TI  - Health care management of adults with Down syndrome.
AB  - The family physician's holistic approach to patients forms the basis of good
      health care for adults with Down syndrome. Patients with Down syndrome are likely
      to have a variety of illnesses, including thyroid disease, diabetes, depression,
      obsessive-compulsive disorder, hearing loss, atlantoaxial subluxation and
      Alzheimer's disease. In addition to routine health screening, patients with Down
      syndrome should be screened for sleep apnea, hypothyroidism, signs and symptoms
      of spinal cord compression and dementia. Patients with Down syndrome may have an
      unusual presentation of an ordinary illness or condition, and behavior changes or
      a loss of function may be the only indication of medical illnesses. Plans for
      long-term living arrangements, estate planning and custody arrangements should be
      discussed with the parents or guardians. Because of improvements in health care
      and better education, and because more people with this condition are being
      raised at home, most adults with Down syndrome can expect to function well enough
      to live in a group home and hold a meaningful job.

PMID- 11578025
TI  - Information from your family doctor. Health issues for adults with Down syndrome.

PMID- 11578026
TI  - Guideline for the management of heart failure caused by systolic dysfunction:
      part II. Treatment.
AB  - Several large clinical trials conducted over the past decade have shown that
      pharmacologic interventions can dramatically reduce the morbidity and mortality
      associated with heart failure. These trials have modified and enhanced the
      therapeutic paradigm for heart failure and extended treatment goals beyond
      limiting congestive symptoms of volume overload. Part II of this two-part article
      presents treatment recommendations for patients with left ventricular systolic
      dysfunction. The authors recommend that, if tolerated and not contraindicated,
      the following agents be used in patients with left ventricular systolic
      dysfunction: an angiotensin-converting enzyme inhibitor in all patients; a beta
      blocker in all patients except those who have symptoms at rest; and
      spironolactone in patients who have symptoms at rest or who have had such
      symptoms within the past six months. Diuretics and digoxin should be reserved, as
      needed, for symptomatic management of heart failure. Other treatments or
      treatment programs may be necessary in individual patients.

PMID- 11578027
TI  - Principles of appropriate antibiotic use: part V. Acute bronchitis.

PMID- 11578028
TI  - Additional comments on screening mammography.

PMID- 11578029
TI  - Additional comments on screening mammography.

PMID- 11578030
TI  - The contemporary ecology of U.S. medical care confirms the importance of primary
      care.
AB  - More women, men and children receive medical care each month in the offices of
      primary care physicians than any other professional setting. There is an urgent
      need for health policies that encourage further innovation and implementation

PMID- 11578031
TI  - Promoting and supporting breastfeeding.

PMID- 11578032
TI  - The ABCs of treating congestive heart failure.

PMID- 11578033
TI  - Concussion in sports.

PMID- 11578034
TI  - Initial management of breastfeeding.
AB  - Breast milk is widely accepted as the ideal source of nutrition for infants. In
      order to ensure success in breastfeeding, it is important that it be initiated as
      early as possible during the neonatal period. This is facilitated by skin-to-skin
      contact between the mother and infant immediately following birth. When possible,
      the infant should be allowed to root and latch on spontaneously within the first
      hour of life. Many common nursery routines such as weighing the infant,
      administration of vitamin K and application of ocular antibiotics can be safely
      delayed until after the initial breastfeeding. Postpartum care practices that
      improve breastfeeding rates include rooming-in, anticipatory guidance about
      breastfeeding problems and the avoidance of formula supplementation and
      pacifiers.

PMID- 11578035
TI  - Information from your family doctor. Tips for breastfeeding success.

PMID- 11578036
TI  - Appropriate antimicrobial prescribing: approaches that limit antibiotic
      resistance.
AB  - Since the introduction of antimicrobial agents, there has been an association
      between antibiotic use and the development of antimicrobial resistance.
      Antibiotic therapy eradicates not only pathogenic organisms but also the
      protective normal flora. This so-called "selective pressure" results in
      colonization with bacteria that are resistant to the original therapy. The result
      has been an increase over the past two decades in antibiotic resistance among
      common bacterial causes of outpatient infections. Several studies have
      demonstrated that a substantial portion of the antibiotics prescribed in the
      outpatient setting are given for viral illnesses or bacterial diseases where the
      benefit of antibacterial therapy is marginal. The reasons for prescribing
      antibiotics in these situations are related to medical and social factors.
      Physicians should be familiar with the clinical situations in which they should
      provide antibiotics and those in which they may safely be withheld. Physicians
      should understand the motivations of patients who are seeking antibiotics and
      provide education, empathy and alternative treatments.

PMID- 11578037
TI  - An overview of the future of non-lethal weapons.
AB  - During the past decade, vast changes have occurred in the geopolitical landscape
      and the nature of the types of conflicts in which technologically developed
      countries have been involved. While the threat of conventional war remains,
      forces have been more frequently deployed in situations that require great
      restraint. Adversaries are often likely to be elusive and commingled with
      noncombatants. There has been some shift in public opinion away from tolerance of
      collateral casualties. Therefore there is a need to be able to apply force while
      limiting casualties. Non-lethal weapons provide part of the solution. Among the
      changes that will influence the future have been studies by the US and NATO
      concerning the use of non-lethal weapons, coincidental with increased funding for
      their development and testing. New concepts and policies have recently been
      formalized. Surprisingly, the most strident objections to the implementation of
      non-lethal weapons have come from organizations that are ostensibly designed to
      protect non-combatants. These arguments are specious and, while technically and
      academically challenging, actually serve to foster an environment that will
      result in the deaths of many more innocent civilians. They misconstrue technology
      with human intent. The reasons for use of force will not abate. Alternatives to
      bombs, missiles, tanks and artillery must therefore be found. Non-lethal weapons
      are not a panacea but do offer the best hope of minimizing casualties while
      allowing nations or alliances the means to use force in protection of national or
      regional interests.

PMID- 11578038
TI  - 'Non-lethal' weapons and international law: three perspectives on the future.
AB  - Literature on 'non-lethal' weapons (NLWs) frequently contains assertions that
      more robust NLW development and use are needed because of the changing nature of
      military operations. These assertions are in opposition to international legal
      analysis of NLWs, which show international law restricting NLW development and
      use. This article examines this tension by briefly analyzing the restrictive
      impact that international law has on NLWs and by elaborating three perspectives
      on what the relationship between NLWs and international law should be. The
      article outlines the moral foundations for existing international law on the use
      of force and armed conflict and then sketches international law's current impact
      on NLW development and use. Next, the article explores the compliance, selective
      and radical change perspectives that emerge from discourse about international
      law and NLWs. The compliance perspective insists that NLWs comply with existing
      rules of international law. The selective change perspective seeks limited
      changes in international law to allow more robust use of NLWs. The radical change
      perspective sees in NLWs the potential to reform radically international law on
      the use of force and armed conflict. Identifying the three perspectives helps
      clarify future choices NLWs may present in international law and suggests that
      the future relationship between NLWs and international law will be more complex,
      controversial and dangerous than people may realize.

PMID- 11578039
TI  - The revolution in military affairs debate and non-lethal weapons.
AB  - This article introduces a discussion on developments in political and strategic
      thinking on the use of existing and emerging weapons (including Non-lethal
      Weapons) and their doctrinal operational implications in the context of present
      trends in international relations. It asserts the need to address both the
      strategic assumptions and the political implications of choosing military-led
      solutions to trends in international social conflict. The so-called Revolution in
      Military Affairs (RMA) must be considered in the light of the current debate on
      the military application of non-lethal weapons (NLWs) to present or future
      conflict. The issue is introduced from a politico-strategic perspective, with a
      critique of the RMA debate as a starting point for discussion of the role of NLWs
      in conflict. Questions are set out for the politicians and strategists who are
      asked to formulate policy based on technology to be used in new political/social
      conflicts. The danger of neglecting other important dimensions of politics and
      strategy vis-a-vis present conflict is noted.

PMID- 11578040
TI  - The role of sub-lethal weapons in human rights abuse.
AB  - This article is based on two recent reports contracted by the European Parliament
      (EP), which assessed sub-lethal weapons as flexible tools of political control.
      It analyses the role and function of existing weapons systems in human rights
      abuses using examples from Indonesia, Israel, Kenya, Northern Ireland and Turkey.
      These weapons are designed to 'appear' rather than 'be' safe and, since they
      augment rather than replace lethal technologies, their use can distort conflicts
      and actually bridge the firewall between use of less-lethal and lethal
      technologies.

PMID- 11578041
TI  - Non-lethal weapons technologies--the case for independent scientific analysis.
AB  - Various technologies have been proposed for non-lethal weapons (NLW), some of
      them credible, or at least plausible, but strong claims were made for others
      without evidence or references. Five such technologies are examined. For the
      chemical and biological examples, detailed information is lacking but the
      diminishing number of such claims over time and general scientific knowledge
      suggest that fulfilment of the promises is improbable. For acoustic weapons, a
      detailed study found that many of the claims are plainly untrue. In this case,
      even wrong values for physiological thresholds were presented. Civil and military
      NLW programmes in the USA put their main emphasis on simple, short-term
      technologies rather than exotic ones. In order to avoid dangers arising from
      unrealistic promises, the concept of preventive arms control should be applied to
      NLW. Its first step is a scientific analysis, investigating the new weapons, the
      propagation of their effects and the effect on the targets. Such detailed studies
      are needed for each proposed NLW technology.

PMID- 11578042
TI  - Future police operations and non-lethal weapons.
AB  - Society has entrusted the police with power and obligation to enforce law,
      maintain order and protect its members and the legal order of society. To be able
      to fulfil these obligations the police need credible means of countering threats
      against these values. Selecting the weapons, or rather use of force instruments,
      presents a multifaceted problem of balancing human considerations, judicial and
      societal requirements with tactical needs and technological possibilities. No
      matter what the incident is, a police-officer is expected to protect the
      innocent, him/herself, colleagues and the object persons and to cause no more
      harm than is justifiable and unavoidable. Unfortunately there is no safe use of
      force and in real life the only option available for resolving certain conflicts
      is some degree of force. Any weapon can be misused but most weapons have a
      legitimate use. Denying legitimate use, as well as allowing uncontrolled use, may
      lead to unnecessary suffering and loss of life. Technology is offering
      interesting alternative possibilities to the police and these must be considered
      with open eyes, bearing in mind that misuse, like torture, is not a property
      inherent to technology but an intentional behaviour of some people. Thorough
      research and fair and credible controls on police weaponry are needed to avert
      the possibility of misuse and to maintain trust.

PMID- 11578043
TI  - Operationalizing non-lethality: a Northern Ireland perspective.
AB  - 'The troubles' over the last 33 years in Northern Ireland have claimed the lives
      of 3,636 people, including 302 police-officers and 644 soldiers. Of these deaths,
      315 were attributed to the military and 52 to the police.(1) Formative experience
      of public disorder within the early parts of the conflict is reviewed. This
      article places the evolution, development and use of baton rounds (rubber and
      plastic bullets) in context and describes the training of police in their use.
      The development of a conflict management strategy which provides synergy with
      community based policing is discussed and the importance of understanding the
      underlying causes of a conflict for law enforcement personnel is emphasized.

PMID- 11578044
TI  - Perspectives and implications for the proliferation of non-lethal weapons in the
      context of contemporary conflict, security interests and arms control.
AB  - This article briefly looks at the characteristics of contemporary conflict and
      the global political arena, particularly from 1989 and the end of the cold war.
      The development of and potential roles for second generation non-lethal weapons
      (NLWs) in war-fighting, peace support operations, and civil policing are
      discussed. There are arguments both for and against further and rapid development
      of NLWs. The question of proliferation and arms control is examined within the
      context of concepts such as the revolution in military affairs (RMA) and factors
      such as the increasing role of non-state actors, current security requirements
      and the problems concerning the implementation and enforcement of current and
      envisaged arms control regimes. Proliferation, which may be vertical or
      horizontal, may not always be seen as a malign process but rather one which
      requires specific ethical and operational perspectives. Proliferation is about
      both technology push and operational requirements. The effectiveness of
      legislative approaches to controlling proliferation, especially to countries
      which are considered to have poor human rights records, is discussed and issues
      about who wants to control NLWs, and why, are raised. Some technologies may be
      seen as less threatening to existing arms control and management treaties and the
      ethical debates which surround them. A concern regarding increasing use of non
      lethal technologies for political oppression is part of this debate. The issues
      are illustrated using India as case study.

PMID- 11578045
TI  - Differential attentional guidance by unattended faces expressing positive and
      negative emotion.
AB  - Four experiments were conducted to evaluate whether focal attention can be guided
      by an analysis of the emotional expression in a face. Participants searched
      displays of 7, 11, 15, and 19 schematic faces for the location of a unique face
      expressing either a positive or a negative emotion located among distractor faces
      expressing a neutral emotion. The slopes of the search functions for locating the
      negative face were shallower than the slopes of the search functions for locating
      the positive face (Experiments 1A and 2A). When the faces were inverted to reduce
      holistic face perception, the slopes of the search functions for locating
      positive and negative faces were not different (Experiments 1B and 2B). The
      results suggest that the emotional expression in a face can be perceived outside
      the focus of attention and can guide focal attention to the location of the face.

PMID- 11578046
TI  - The effects of abrupt onset of 2-D and 3-D distractors on prehension movements.
AB  - This article includes two experiments aimed at investigating how two-dimensional
      (2-D) and three-dimensional (3-D) distractors affect the kinematics of prehension
      and aiming movements in order to understand the attentional processes involved in
      visuomotor control. In Experiment 1, subjects grasped large targets in the
      presence of both large and small 3-D distractors and their corresponding 2-D
      photographs. The distractors appeared for either 10 sec or appeared
      simultaneously with the target presentation. It was found that reach and grasp
      kinematics were influenced primarily by the small, suddenly appearing 3-D
      distractors. In Experiment 2, the purpose was to examine the conclusion that
      competition between objects (target and distractor) is related to the behavioral
      goal of the task. Experiment 2 is a replication of Experiment 1, with the
      exception that pointing movements were made instead of grasping movements.
      Results show that both 3-D and 2-D distractors interfered with pointing
      kinematics, supporting the hypothesis that attentional mechanisms are related to
      the goal of the task.

PMID- 11578047
TI  - Statistical and information properties of head direction cells.
AB  - The human channel capacity for identifying sensory stimuli is compared with
      channel capacities based on neurophysiological findings. Studies have shown that
      cells in the postsubiculum (PoS) and the anterior dorsal thalamus (ADN) of the
      rat discharge as a function of the animal's head direction in the horizontal
      plane. We compute the statistical properties of the firing rates of head
      direction (HD) cells and the potential amount of information transmitted by these
      cells according to two theoretical models. The ceU response model for single
      cells indicates that information transmitted is much less than 0.5 bits. The
      population response model developed for cell ensembles generates values in the
      range of 1-3.2 bits, suggesting that a cell population can distinguish between
      two and nine head directions, depending on the value used for the standard
      deviation of directions over which a cell fires. These values are similar to
      those found in human psychophysical studies of the channel capacity for
      unidimensional sensory attributes.

PMID- 11578048
TI  - The combined influence of binocular disparity and shading on pictorial shape.
AB  - The combined influence of binocular disparity and shading on pictorial shape was
      studied. Stimuli were several pairs of stereo photographs of real objects. The
      stereo base was 0, 7, or 14 cm, and the location of the light source was varied
      over three positions (one from about the viewpoint of the camera, one about
      perpendicular to the line of sight, and one in between the two). Therefore, in
      total, nine different combinations were studied. Subjects had to perform surface
      attitude settings at about 300 positions in the image plane. From the settings,
      depth maps were calculated on which a principal components analysis was
      performed. It was found that three components were enough to account for at least
      97.8% of the variance in the data. The first component accounted for shape
      constancy. The effects of the two cues could be isolated as a linear combination
      of the other two components. The effects of the disparity and the shading cue
      variation were found to combine in almost linear fashion.

PMID- 11578049
TI  - Effects of luminance oscillations on simulated lightness discriminations.
AB  - The speed of processes underlying lightness constancy was studied by having
      observers discriminate small differences in simulated lightness under an
      oscillating illumination. The period of oscillation varied from 0.25 to 120 sec.
      The target was a 1 degrees square which appeared for 150 msec at random intervals
      either directly against a uniform background or separated from the background by
      a 1 degrees dark gap. When the target and background were adjacent to each other,
      discrimination accuracy approached control levels (fixed illumination) at all but
      the shortest periods of oscillation. When the gap was introduced, accuracy
      increased as the period of oscillation increased, but never approached control
      levels. The results suggest that a fast local contrast mechanism is the primary
      mediator of lightness constancy for this task, but that there is also a slower
      mechanism that may be related to adaptation.

PMID- 11578050
TI  - Negative priming and perceptual fluency: more than what meets the eye.
AB  - In two priming experiments, we manipulated the perceptual quality of the target
      or the distractor on the prime trial; the stimuli were repeated or novel.
      Negative priming was found to be contingent on stimulus repetition, because it
      was obtained with repeated items but not with novel items. Prime trial perceptual
      degradation modulated negative priming for repeated items but had no effect on
      priming in ignored repetition conditions using novel stimuli. These patterns were
      obtained even when the effect of perceptual degradation was (1) greater than the
      effect of stimulus repetition and (2) greater for novel words than for repeated
      words. Although stimulus repetition increases perceptual fluency, the activation
      of perceptual representations by itself is not sufficient to produce negative
      priming. Instead, we suggest that negative priming is a manifestation of an
      activation-sensitive inhibitory mechanism that functions to reduce response
      competition.

PMID- 11578051
TI  - Examining location-based and object-based components of inhibition of return in
      static displays.
AB  - Tipper and Colleagues (e.g., Jordan & Tipper, 1998; Tipper, Driver, & Weaver,
      1991; Tipper, Weaver, Jerreat, & Burak, 1994) have provided support for
      inhibition of return (IOR) being composed of a location-based and an object-based
      component. They were able to separate out the effects of location-based and
      object-based IOR by using complex displays and displays that involved moving the
      cued object. The present study was designed to further examine the object- and
      location-based components of IOR in static displays. Three experiments were
      conducted that looked at the presence or absence of placeholder boxes on IOR. The
      first experiment was designed to replicate the results of Jordan and Tipper by
      presenting both objects and no-objects in the same display. In the second
      experiment, trials were blocked, and in the third experiment trials were
      presented in a random order. Overall, the results are inconsistent with the
      notion that independent object-based and location-based IOR components combine to
      produce the overall IOR effect and that additive effects are realized due to the
      context in which the trials are presented. We propose that a single inhibitory
      mechanism can account for the data.

PMID- 11578052
TI  - A Thurstonian model for the dual pair (4IAX) discrimination method.
AB  - In the dual pair method, the subject is presented with two stimuli in two pairs:
      One pair is composed of two samples of the same stimulus; the other pair is
      composed of two samples of different stimuli, one being the same as that in the
      identical pair. The task of the judge is to select the most different pair. The
      psychometric function for the dual pair method is derived and expressed in terms
      of a singly noncentral beta distribution. A table is provided that connects a
      measure of the degree of difference, d, to the probability of a correct response.
      This table assumes an unbiased observer and differencing decision rule. A table
      is provided to give an estimate of the variance of d , the experimental estimate
      of d. The power of the dual pair method is also investigated, and a formula to
      determine the sample size required to meet Type I and Type II error
      specifications is given. The dual pair method appears to be slightly less
      powerful than the duo-trio and the triangular methods. Experimental investigation
      is needed to explore the dual pair in applied research work.

PMID- 11578053
TI  - Indices of response bias in the same-different experiment.
AB  - The same-different experiment is popular for assessing perceptual performance,
      including the performance of people with neuropsychological deficits. Although
      the measurement of accuracy with this experiment is now well understood, the
      measurement of response bias remains problematic. Reformulating the decision
      space for the experiment can yield new bias indices that are analogous to, but
      numerically different from, those of the more familiar yes-no experiment. Isobias
      curves that show how hit rate covaries with false alarm rate for constant bias
      but varying accuracy are presented for eight indices, and best-fitting parameters
      of the isobias functions are determined for a set of experimental data. The
      theoretical status of the bias indices and their relation to other formulations
      are reviewed.

PMID- 11578054
TI  - A clarification of self-terminating versus exhaustive variances in serial and
      parallel models.
AB  - A recent study published in Perception & Psychophysics (Donnelly, Found, &
      Miller, 1999) employs response time (RT) variances (in the form of standard
      deviations) in addition to mean RTs. Variances can contribute greatly to model
      testing. However, there is a danger of perpetuating the kinds of logical and
      methodological errors that have long attended research employing mean RTs alone.
      This commentary clarifies the theoretical and methodological issues, points out
      some new results concerning variability in search processes, and indicates how to
      resolve the global and specific challenges associated with identifying
      psychological mechanisms.

PMID- 11578055
TI  - Understanding priming of color-singleton search: roles of attention at encoding
      and "retrieval".
AB  - We investigated how the performance of a color-singleton search (the search for a
      single odd-colored item among homogeneously colored distractors) left a
      persistent memory trace (lasting up to six intervening trials or approximately 17
      sec) that facilitated a subsequent color-singleton search (when the same target
      distractor color combination was repeated). Specifically, we investigated the
      roles of attention in the encoding and "retrieval" stages of this priming effect
      by intermixing trials in which the target location was precued by an onset cue.
      We found that the encoding of both target and distractor colors was automatic in
      that whether or not observers had to use color in locating the target in the
      preceding trial did not substantially affect priming. However, priming required
      that the color-singleton item be attended in the preceding trial. Once a color
      singleton display was encoded, our results indicated that priming facilitated the
      direction of attention to the color-singleton target on a subsequent trial. In
      short, when a color-singleton item happened to be a critical item to be attended
      in one situation, another color-singleton item defined by the same color
      combination tended to attract attention in subsequent encounters.

PMID- 11578056
TI  - A formal version of the Guided Search (GS2) model.
AB  - Guided Search 2 (GS2) is currently one of the most detailed models of visual
      search and has been used to predict search times for different stimulus
      conditions by means of detailed computer simulations. The present article goes a
      step further and presents formulas that allow for the calculation of the search
      times and their variances. Moreover, these formulas can be applied to fit GS2 to
      data. An example is provided in which GS2 is fitted to search functions
      representing search asymmetries.

PMID- 11578057
TI  - Influence of single and multiple onset distractors on visual search for singleton
      targets.
AB  - In three experiments, we examined attentional and oculomotor capture by single
      and multiple abrupt onsets in a singleton search paradigm. Subjects were
      instructed to move their eyes as quickly as possible to a color singleton target
      and to identify a small letter located inside of it. In Experiment 1, task
      irrelevant sudden onsets appeared simultaneously on half the trials with the
      presentation of the color singleton target. Response times (RTs) were longer when
      onsets appeared in the display regardless of the number of onsets. Eye-scan
      strategies were also disrupted by the appearance of the onset distractors,
      although the proportion of trials on which the eyes were directed to the onsets
      was the same regardless of the number of onsets. In Experiment 2, we manipulated
      the time of presentation of two task-irrelevant onsets in order to further
      examine whether multiple onsets would be attended and fixated prior to attending
      a color singleton target. Again, subjects made a saccade to a task-irrelevant
      onset on a substantial proportion of trials prior to fixating the target.
      However, saccades to the second onset were rare. Experiment 3 served as a
      replication of Experiment 1 but without the requirement for subjects to move
      their eyes to detect and identify the singleton target. The RT results were
      consistent with those in Experiment 1; dual onsets had no larger an effect on
      response speed than single onset distractors. These data are discussed in terms
      of the interaction between top-down and bottom-up control of attention and the
      eyes.

PMID- 11578058
TI  - Higher order sequential effects in psychophysical judgments.
AB  - We found that the depth of sequential effects depends on the judgment task. An
      experiment with squares indicated that stimulus-response pairs up to two trials
      back were included in the judgment process when subjects were required to make
      category judgments of size, whereas only the immediately preceding event was
      incorporated when subjects were making magnitude estimations. In the case of
      category judgment, interactions between the current stimulus and prior stimuli as
      well as configural effects indicated that events one and two trials back meet an
      equivalent function in the judgment process and that these events may jointly
      operate in one trial. These findings can be explained by a class of models that
      assume that the position of preceding stimuli relative to the current stimulus is
      decisive in the judgment process. The multiple-standards model is a
      representative of this class according to which there are two types of standards:
      (1) the endpoints of the range as long-term standards and (2) traces of preceding
      stimuli as short-term standards.

PMID- 11578059
TI  - Attentional capture with various distractor and target types.
AB  - Effects of nonpredictive distractors that involved changes in luminance, size, or
      shape were examined in three experiments. In Experiment 1, with two types of
      distractors (onsets and offsets), accuracy was better on trials when the
      distractor was near the location of either an offset or an onset target than on
      trials when the distractor was in a different location from that of the target,
      demonstrating attentional capture. Capture occurred both when the type of target
      (onset or offset) was blocked and therefore predictable and also when the type of
      target was mixed within blocks and therefore not predictable. Further experiments
      indicated that distractors captured attention even when the change to distractor
      did not create a new perceptual object. Neither a singleton-detection mode, nor a
      contingent involuntary orienting hypothesis, nor creation of a new object seems
      to explain all of these data adequately. Rather, capture may depend on a number
      of factors in the task.

PMID- 11578060
TI  - Is evidence for late selection due to automatic or attentional processing of
      stimulus identities?
AB  - This study determined whether evidence for late selection is due to attention
      processing or to processing by an automatic system that is separate from
      attention (two systems framework; Eriksen, Webb, & Fournier, 1990). The task was
      a two-choice discrimination of a target that appeared in one of two sequentially
      cued locations in an eight-letter visual display. Attention was directed to the
      first cued location (cue 1), and whether identification processing occurred at a
      different location before the second cue (cue 2) directed attention there was
      determined. Cue validity varied across two experiments, and critical trials were
      those in which the target appeared at cue 2. For these trials, the target was
      preceded by a letter (either identical, neutral, or incompatible) that changed to
      the target at various time intervals following cue 2. Automatic identification
      was assumed if the incompatible letter interfered with response to the target
      when it appeared only before cue 2 onset and independent of cue validity. The
      incompatible letter appearing only before cue 2 onset interfered with the target
      when the target occurred equally often at cue 1 and cue 2, but not when the
      target occurred at cue 1 70% and at cue 2 30% of the time. This disconfirms the
      two systems framework and suggests that attention is required for spatial form
      processing and response competition.

PMID- 11578061
TI  - Precancerous lesions of the colorectum.

PMID- 11578062
TI  - Immunohistochemical study of p53, c-erbB-2, and PCNA in barrett's esophagus with
      dysplasia and adenocarcinoma arising from experimental acid or alkaline reflux
      model.
AB  - PURPOSE: An immunohistochemical study of p53, c-erbB-2, and proliferating cell
      nuclear antigen (PCNA) in Barrett's esophagus with dysplasia and adenocarcinoma,
      arising from experimental acid or alkaline reflux, was performed in dogs.
      METHODS: Cardiectomy was performed in group A (n = 26) as an acid reflux model,
      and total gastrectomy was performed in group B (n = 24) as an alkaline reflux
      model. After surgery, the esophageal mucosa was observed and biopsied
      endoscopically every 3 months over a period of 6 years. Immunohistochemical
      staining of p53. c-erbB-2, and PCNA was performed, using biopsied specimens.
      RESULTS: In group A, Barrett's esophagus developed in 14 of the 26 dogs. Low
      grade dysplasia occurred in 5 of the 26 dogs, and in 1 of these 5 dogs, it
      developed into high-grade dysplasia. In this animal, adenocarcinoma arose 63
      months after the operation. In group B, Barrett's esophagus developed in 10 of
      the 24 dogs. Low-grade dysplasia was observed in 4 of the 24 dogs. In 1 of these
      4 dogs, the dysplasia became high-grade and adenocarcinoma occurred 66 months
      after the operation. In group A, PCNA was positive in adenocarcinoma; the PCNA
      labeling index (LI) was 58. c-erbB-2 and p53 were negative in all animals in
      group A. In group B, PCNA was positive in Barrett's esophagus with high-grade
      dysplasia and adenocarcinoma; the PCNA LI was 77. p53 was positive in
      adenocarcinoma. c-erbB-2 was negative in adenocarcinoma. CONCLUSIONS; The results
      of this study provided evidence of the dysplasia-carcinoma sequence arising from
      alkaline reflux, as well as from acid reflux. To the best of our knowledge, this
      is the first report of the use of an alkaline reflux model and a 6-year study
      using dogs to observe the course of Barrett's esophagus.

PMID- 11578063
TI  - A low 13C-urea breath test value is associated with increased risk of gastric
      cancer.
AB  - PURPOSE: The 13C-urea breath test (UBT) is considered to be the most accurate way
      of diagnosing Helicobacter pylori infection. Values are affected by H. pylori
      infection and by the severity of atrophic gastritis. Our objective was to
      determine the association of UBT values with gastric cancer, and to evaluate the
      risk of gastric cancer in terms of UBT values. METHODS: Our study involved 413
      consecutive patients who had undergone esophagogastroduodenal examination and the
      UBT test. RESULTS: Of the 398 patients with positive UBT results, atrophy and
      intestinal metaplasia scores in both antrum and corpus were significantly higher
      in patients with gastric cancer than in those with gastritis, duodenal ulcer, and
      gastric ulcer. The UBT value related to gastric cancer (22.01 +/- 1.89%o) was
      significantly lower than that for gastritis (35.19 +/- 1.53%o; P < 0.01),
      duodenal ulcer (29.01 +/- 1.97%; P < 0.05), or gastric ulcer (30.79 +/- 2.83%; P
      < 0.05). When the UBT values were less than 20%, increases in the risk of gastric
      cancer correlated with decreasing UBT values. CONCLUSIONS; These findings
      indicate that the UBT value related to gastric cancer is significantly lower than
      that for gastritis, duodenal ulcer, or gastric ulcer in H. pylori-positive
      patients. Low UBT values were associated with the risk of gastric cancer.

PMID- 11578064
TI  - A 13C-urea breath test in children with helicobacter pylori infection: assessment
      of eradication therapy and follow-up after treatment.
AB  - PURPOSE: Our aim was to evaluate the usefulness of the 13C-urea breath test (UBT)
      for the diagnosis of Helicobacter pylori infection, for assessment of the
      efficacy of eradication therapy, and for post-treatment follow-up in children.
      METHODS: Seventy-two patients who underwent endoscopy for symptoms related to the
      upper gastrointestinal tract were examined by rapid urease test, histology, and
      culture. The patients were also studied with serology and UBT. RESULTS: Forty
      seven of the 72 patients were diagnosed with H. pylori infection, based on the
      results of biopsy-based tests and serology. As an initial diagnostic test to
      detect H. pylori infection, the sensitivity of the UBT was 95%, which was
      comparable with that of histology (94%), rapid urease test (96%), and serology
      (91%) and was greater than that of culture (79%). The specificity of the UBT was
      100%, which was comparable with that of the other four tests. The efficacy of
      eradication therapy was assessed by biopsy-based tests and the UBT in 24 H.
      pylori-positive patients. For this purpose, the sensitivities of UBT and
      histology were 100%, while the sensitivities of culture and the rapid urease test
      were 88%. The specificity was 100% for all of these tests. Eleven patients were
      assessed by biopsy-based tests and UBT after more than 6 months of post-treatment
      follow-up. There were no discordances between the results of the UBT and those of
      the biopsy-based tests in any of the patients. CONCLUSIONS: The UBT may be useful
      for detecting H. pylori infection in children with upper gastrointestinal tract
      symptoms, for assessment of the efficacy of eradication therapy, and for the
      follow-up evaluation of patients after the therapy.

PMID- 11578065
TI  - Genetic mutations in exons 3 and 4 of the pancreatic secretory trypsin inhibitor
      in patients with pancreatitis.
AB  - PURPOSE: We hypothesized that mutations in the pancreatic secretory trypsin
      inhibitor (PSTI) gene could promote autodigestion, leading to acute or chronic
      pancreatitis. Our investigation involved mutation analysis of the PSTI gene in
      patients with acute or chronic pancreatitis. METHODS: Mutation analysis for the
      PSTI gene was performed in patients with acute or chronic pancreatitis. Unrelated
      healthy volunteers and family members of a chronic pancreatitis patient with
      point mutations in the PSTI gene were also analyzed. RESULTS: Two types of single
      point mutation in the PSTI gene were observed in one patient with chronic
      pancreatitis: 34Asn (AAT)-to-Ser (AGT) (101 A > G N34S: N34S) in exon 3, and
      67Arg (CGC)-to-Cys (TGC) (199 C > T R67C: R67C) in exon 4. No mutations with
      amino-acid substitution were found in other patients or in the volunteer group.
      In the patient with the PSTI gene mutations, no additional mutations were
      observed in the cationic trypsinogen gene. The family study revealed that the
      mother and a maternal uncle were homozygotes for the N34S mutation, while the
      father and brother were compound heterozygotes for the N34S and R67C mutations.
      The uncle (N34S/N34S) showed clinical manifestations of pancreatitis, but the
      other family members did not. CONCLUSIONS: The N34S mutation may cause a
      predisposition to pancreatitis, with incomplete penetrance. However, with the
      limited information available, it is not known whether the R67C mutation promotes
      pancreatitis.

PMID- 11578066
TI  - Differential diagnosis of large-sized pedunculated polypoid lesions of the
      gallbladder by endoscopic ultrasonography: a prospective study.
AB  - PURPOSE: We have previously reported the effectiveness of endoscopic
      ultrasonography (EUS) for the differential diagnosis of pedunculated polypoid
      lesions of the gallbladder, based on retrospective studies using resected
      specimens. We proposed the following diagnostic criteria for EUS findings: when
      the contour of a lesion is nodular or smooth, the lesion is diagnosed as a
      neoplasm, and when a lesion has a granular contour, it is diagnosed as a
      nonneoplasm. The present study was designed to verify the clinical utility of our
      EUS ctiteria prospectively. METHODS: Forty-six consecutive patients with
      pedunculated polypoid lesions of the gallbladder 10mm or greater in size
      diagnosed as nonneoplasms at the initial EUS, all of whom underwent follow-up
      examinations, were enrolled in this study. The occurrence of changes in these
      lesions during the observation period was examined. RESULTS: No evident changes
      in lesions were observed in 43 of the 46 patients. Spontaneous self-detachment of
      lesions was recognized during the observation period in the other 3 patients.
      CONCLUSIONS: EUS is useful for determining treatment indications for pedunculated
      polypoid lesions of the gallbladder, even when the lesions are large, and
      contributes to avoiding unnecessary surgery.

PMID- 11578067
TI  - Psoas abscess and cellulitis of the right gluteal region resulting from carcinoma
      of the cecum.
AB  - Although retroperitoneal or psoas abscess is an unusual clinical problem, the
      insidious and occult characteristics of this abscess sometimes cause diagnostic
      delays, resulting in considerably high morbidity and mortality. In particular,
      psoas abscess caused by perforated colon carcinoma is uncommon. We report a case
      of psoas abscess caused by a carcinoma of the cecum. A 72-year-old Japanese woman
      was admitted to our hospital, with pain in the right groin and buttock. The pain
      had appeared 6 months before admission, and the symptoms had then been relieved
      by oral antibiotics. On March 25, 1999, inflammatory signs in the right buttock
      indicated localized cellulitis, and incision and drainage was performed at a
      local hospital. The patient was referred to our hospital on the same day. On
      admission to our hospital, computed tomography (CT) scan revealed a thick right
      sided colonic wall and enlargement of the right ileopsoas muscle. Barium enema
      and colonofiberscopy revealed an ulcerated tumor occupying the entire
      circumference of the cecum. A retroperitoneal abscess and fistula had been formed
      by the retroperitoneal perforation of cecum carcinoma: surgical resection was
      performed after remission of the local inflammatory signs. Operative findings
      indicated that the cancerous lesion and its surrounding tissues were firmly
      attached to the right iliopsoas and major psoas muscle, and en-bloc resection,
      including adjacent muscular tissue, was performed. The fact that carcinoma of the
      colon could be a cause of psoas abscess and cellulitis in the gluteal region
      should be considered when an unexplained psoas abscess is diagnosed.

PMID- 11578068
TI  - Pseudomembranous colitis without diarrhea presenting clinically as acute
      intestinal pseudo-obstruction.
AB  - Pseudomembranous colitis usually presents with diarrhea in a clinical setting of
      recent antibiotic use. It is uncommon to see it as a cause of obstipation and
      colonic pseudo-obstruction. We report an unusual case of an elderly woman with
      hypertension, congestive heart failure, chronic obstructive pulmonary disease,
      chronic renal insufficiency, and diabetes mellitus, who was admitted with fever,
      abdominal pain, and distension without diarrhea. She presented with decreased
      stool frequency and obstipation. She did not respond to conservative management.
      Colonoscopy revealed a picture of pseudomembranous colitis, and Clostridium
      difficile toxin was positive. She responded well to metronidazole therapy.

PMID- 11578069
TI  - Reactivation of latently infected hepatitis B virus in a leukemia patient with
      antibodies to hepatitis B core antigen.
AB  - A 66-year-old man with chronic B-cell leukemia who had antibody to hepatitis B
      core antigen (anti-HBc) but not hepatitis B surface antigen (HBsAg) suffered from
      lethal hepatitis caused by hepatitis B virus (HBV) reactivation. He initially
      lacked circulating viral genomes in his sera and did not have a past history of
      liver dysfunction. In this patient, the immunosuppressive condition introduced by
      disease progression of leukemia induced reactivation of dormant HBV, and the
      withdrawal of chemotherapy resulted in fatal liver failure. Mutation-specific
      assay based on competitive polymerase chain reaction (PCR) and sequencing
      analyses revealed the predominant reactivation of an HBV strain with missence
      mutation (point mutation G-to-A at nucleotide 1896) in the precore regions, as
      well as point mutations in the core promoter regions. Therefore, it is important
      to note the risk of HBV reactivation, with resulting lethal hepatic failure, in
      anti-HBc-positive healthy individuals, even when they lack HBsAg. who receive
      immunomodulating therapy.

PMID- 11578070
TI  - Living-related partial liver transplantation for decompensated hepatitis B
      without reactivation of hepatitis B in the following 30 months.
AB  - We report a case of living-related partial liver transplantation for
      decompensated hepatitis B without reactivation of hepatitis B in the following 30
      months, and we analyze the factors that indicate a favorable prognosis for
      transplantation. The 42-year-old female patient received continuously
      administered lamivudine before transplantation, and hepatitis B virus
      immunoglobulin (HBIG) from the anhepatic phase to the present. Currently, she
      shows a normal aminotransferase level and is negative for hepatitis B surface
      antigen and hepatitis B virus (HBV) DNA by polymerase chain reaction
      amplification. Sequence analysis was performed. The entire precore/core region
      and part of the polymerase region of HBV were sequenced by a direct sequencing
      method after polymerase chain reaction. No specific mutation was found in these
      regions. These observations show that the key factors in the long-term successful
      treatment of this patient appear to be the combination therapy of lamivudine and
      HBIG that the patient received from around the time of the transplantation.
      Furthermore, the lack of specific mutations, including lamivudine resistant
      mutations, is likely to represent an additional factor in the effectiveness of
      this treatment.

PMID- 11578071
TI  - Sonographic findings of wandering spleen.

PMID- 11578072
TI  - Do point mutations in the PSTI (SPINK1) gene truly contribute to the pathogenesis
      of chronic pancreatitis?

PMID- 11578073
TI  - How to determine the surgical indications for pedunculated polypoid lesions of
      the gallbladder.

PMID- 11578074
TI  - Exploring the link between time to collision and representational momentum.
AB  - Previous research has shown that when a moving object is occluded prior to
      collision with another stationary object, observers tend to consistently
      underestimate the physical/actual time to collision (TTC). We examined whether
      mislocalization of the initial point of disappearance plays any role in this
      underestimation. To assess the contribution of mislocalization, we coupled a
      standard TTC paradigm with a representational-momentum paradigm. Representational
      momentum refers to the tendency to mislocalize the remembered stopping point of a
      moving object as being too far forward along an actual or implied path of motion.
      Using identical displays we found large representational-momentum shifts and
      consistent underestimation of TTC. When the displays were modified to
      disambiguate the point of disappearance, representational momentum was absent or
      significantly reduced and underestimates of TTC were effectively eliminated.
      These results strongly suggest that the represented point of disappearance is an
      important factor in TTC estimation and that systematic forward displacement of
      this point may partially explain frequently observed underestimation.

PMID- 11578075
TI  - A comment on the Anderson (1997), the Todorovic (1997), and the Ross and Pessoa
      (2000) explanations of White's effect.

PMID- 11578076
TI  - Seeing oneself.

PMID- 11578077
TI  - Beyond junctions: nonlocal form constraints on motion interpretation.
AB  - Because of the aperture problem, local motion measurements must be combined
      across space. However, not all motions should be combined. Some arise from
      distinct objects and should be segregated, and some are due to occlusion and
      should be discounted because they are spurious. Humans have little difficulty
      ignoring spurious motions at occlusions and correctly integrating object motion,
      and are evidently making use of form information to do so. There is a large body
      of theoretical and empirical evidence supporting the importance of form processes
      involving junctions in the way motion is integrated. To assess the role of more
      complex form analysis, we manipulated nonlocal form cues that could be varied
      independently of local junctions. Using variants on diamond and plaid stimuli
      used in previous studies, we found that manipulations distant from the junctions
      themselves could cause large changes in motion interpretation. Nonlocal
      information often overrides the integration decisions that would be expected from
      local cues. The mechanisms implicated appear to involve surface segmentation,
      amodal completion, and depth ordering.

PMID- 11578078
TI  - Recognition of point-light biological motion displays by young children.
AB  - We tested the ability of children 3-5 years of age to recognise biological motion
      displays. Children and adults were presented with moving point-light
      configurations depicting a walking person, four-legged animals (dogs), and a
      bird. Participants were able to reliably recognise displays with biological
      motion, but failed in the identification of a static (four consecutive frames
      taken from each sequence) version. The results indicate that, irrespective of the
      highly reduced and unusual structural information available in point-light
      displays, biological motion is sufficient for reliable recognition of human and
      non-human forms at an age as early as 3 years. Moreover, 5-year-olds exhibit the
      ceiling level of recognition. The findings are discussed in the context of the
      neuropsychological and brain mechanisms involved in biological motion perception.

PMID- 11578080
TI  - Mental imagery of visual motion modifies the perception of roll-vection
      stimulation.
AB  - When viewing a wide-angle visual display, which rotates in the frontoparallel
      plane around the line of sight, observers experience an illusory shift of the
      direction of gravity; this shift leads to an apparent tilt of the body and
      displaces allocentric space coordinates. In this study, subjects adjusted an
      indicator to the apparent horizontal while viewing a rotating display. To
      determine whether top down processes could affect the illusion, the subjects were
      asked to visualize a rotating configuration of dots onto a blank central portion
      of the moving visual field. Visualizing dots and actually viewing the dots
      deflected the spatial judgment in very similar ways. These results demonstrate
      that top down processing can affect allocentric space coordinates.

PMID- 11578079
TI  - Visual mislocalisation induced by translational and radial background motion.
AB  - Three experiments were conducted to explore how translational and radial
      background motion affected visual localisation. In experiment 1, subjects were
      asked to indicate the apparent position of a small spot of light flashing against
      a background of vertical stripes, at a varying point in time before and after
      rapid translational motion of the background to the left or right. When the spot
      was flashed before the background motion, subjects mislocalised it toward the
      central fixation point. An interesting finding was that this mislocalisation
      occurred in most cases when the background moved in the direction opposite to the
      visual half-field in which the spot was flashed. That is to say, a spot flashed
      on the right side of the fixation point was mislocalised when its background
      moved to the left, and not when it moved to the right; and the converse was also
      true. In experiment 2, concentric circles were used as the background, and moved
      in a contracting or expanding direction. The results indicated that
      mislocalisation toward the central fixation point occurred when a spot was
      flashed before contracting motion of the background. The same mislocalisation was
      observed for the spot flashed in the lower visual field, but not when it was
      flashed in the upper visual field (experiment 3). It is concluded that the
      mislocalisation is a visual illusion induced by a transient background motion
      toward the central fixation point.

PMID- 11578081
TI  - Perceptual continuation and depth in visual phantoms can be explained by
      perceptual transparency.
AB  - We try to explain perceptual continuation and depth in the visual-phantom
      illusion in terms of perceptual transparency. Perceptual continuation of inducing
      gratings across the occluder in stationary phantoms could be explained with
      unique transparency, a notion proposed by Anderson (1997 Perception 26 419-453).
      This view is consistent with a number of previous reports including that of
      McCourt (1994 Vision Research 34 1609-1617) who criticized the stationary phantom
      illusion from the viewpoint of his counterphase lightness induction or grating
      induction, which might involve invalid transparency. Here we confirm that the
      photopic phantom illusion (Kitaoka et al, 1999 Perception 28 825-834) really
      gives in-phase lightness induction and involves bistable transparency. It is thus
      suggested that perceptual continuation and depth in the visual-phantom illusion
      depend on perceptual transparency.

PMID- 11578082
TI  - Effect of photographic negation on matching the expressions and identities of
      faces.
AB  - In four experiments, participants made speeded same-different responses to pairs
      of face photographs showing the same woman or different women with the same
      expression or different expressions. Compared with responses to positive pairs,
      negative pairs were matched more slowly on identity than on expression. A
      secondary finding showed that face expressions (same, different) influenced
      identity responses, and identities influenced expression responses, equally for
      positive and negative pairs. The independence of this irrelevant-dimension effect
      from the contrast effect supports the conclusion required by the main finding
      that negation slows perceptual encoding of surface-based information used for
      identification more than it does encoding of edge-based information used for
      expression recognition.

PMID- 11578083
TI  - Visuospatial attention: the role of target contrast and task difficulty when
      assessing the effects of cues.
AB  - Cueing paradigms have become popular in assessing the processes of attention. In
      two experiments we manipulated (i) the contrast of the target, and (ii) the
      similarity between the targets discriminated. We used a cue that would isolate
      the exogenous component of attention. Both a reduction in target contrast and an
      increase in target similarity raised overall reaction times by a similar amount;
      however, the target contrast manipulation produced a much greater cueing effect
      compared with the target similarity manipulation. The results suggest that
      manipulation of target contrast changes the attention cueing effect at a stage of
      attracting attention to a location of the target (the 'move' stage), rather than
      at a later processing stage.

PMID- 11578084
TI  - Characterising the visual buffer: real-world evidence for overwriting early in
      each fixation.
AB  - What happens to the pictorial content of fixations when we move our eyes?
      Previous studies demonstrate that observers are very poor at detecting changes in
      natural scenes that occur across saccades, blinks, and artificial interruptions
      ('change blindness'). They suggest that the visual 'snapshots' of what is on the
      retina during a fixation are not retained and fused over successive fixations. I
      find similar results when volunteers are performing the complex real-life task of
      making a cup of tea. Volunteers can access the snapshot of the current fixation
      but not those of previous fixations. I suggest that volunteers are reporting the
      content of a low-level visual store that holds a veridical snapshot of the
      current fixation, rather than the retina itself. The snapshots are not 'wiped' by
      the saccade and remain in the buffer until they are overwritten by a new
      snapshot. The overwrite occurs in an all-or-none manner and can be at any time
      within the first 400 ms of each new fixation, with 50% of overwrites being within
      the first 100 ms.

PMID- 11578085
TI  - Plasmodium falciparum: linkage disequilibrium between loci in chromosomes 7 and 5
      and chloroquine selective pressure in Northern Nigeria.
AB  - In view of the recent discovery (Molecular Cell 6, 861-871) of a (Lys76Thr) codon
      change in gene pfcrt on chromosome 7 which determines in vitro chloroquine
      resistance in Plasmodium falciparum, we have re-examined samples taken before
      treatment in our study in Zaria, Northern Nigeria (Parasitology, 119, 343-348).
      Drug resistance was present in 5/5 cases where the pfcrt 76Thr codon change was
      seen (100% positive predictive value). Drug sensitivity was found in 26/28 cases
      where the change was absent (93% negative predictive value). Allele pfcrt 76Thr
      showed strong linkage disequilibrium with pfmdr1 Tyr86 on chromosome 5, more
      complete than that between pfcrt and cg2 alleles situated between recombination
      cross-over points on chromosome 7. Physical linkage of cg2 with pfcrt may account
      for linkage disequilibrium between their alleles but in the case of genes pfmdr1
      and pfcrt, on different chromosomes, it is likely that this is maintained
      epistatically through the selective pressure of chloroquine.

PMID- 11578086
TI  - Anti-SAG1 peptide antibodies inhibit the penetration of Toxoplasma gondii
      tachyzoites into enterocyte cell lines.
AB  - The initial attachment of Toxoplasma tachyzoites to the target host cell is an
      important event in the life-cycle of the parasite and a critical stage in
      infection. Previous studies have shown that polyclonal antibodies directed
      against the major surface antigen of Toxoplasma gondii (SAG1) inhibit the
      infection of enterocyte cell lines. Here, we demonstrate that antibodies raised
      against a central peptide (V41T) of SAG1 and the SAGI protein itself are able to
      inhibit the infection of various cell lines by the tachyzoites. Antibodies
      directed against SAG1 peptides were used to define a site on the SAGI antigen
      that interacts with the host cell. The epitope carried by V41T was identified on
      the tachyzoite surface by immunofluorescence. The peptide sequence seems to be
      conserved in all the members of the SAGI Related Sequence family (SRS). Using
      undifferentiated and differentiated Caco-2 cells, we found that tachyzoites enter
      preferentially via the basolateral side of the cell. These findings highlight the
      role of the SRS family members in the mediation of host cell invasion.

PMID- 11578087
TI  - Programmed cell death in a human intestinal parasite, Blastocystis hominis.
AB  - Although programmed cell death (PCD) has been associated with multicellular
      organisms, there have been more reports of its presence in some protozoans. Our
      study shows the existence of PCD in an intestinal protozoan, Blastocystis
      hominis. Light and electron microscopy, biochemical and flow cytometry studies
      showed apoptosis-like death in B. hominis cells exposed to a cytotoxic monoclonal
      antibody (MAb 1D5). B. hominis cells displayed key morphological and biochemical
      features of apoptosis, namely, nuclear condensation and in situ fragmentation,
      reduced cytoplasmic volume, some externalization of phosphatidylserine and
      maintenance of plasma membrane integrity. No oligonucleosomal DNA laddering was
      observed in gel electrophoresis. This study supports earlier observations that
      the cellular machinery that is required to carry out PCD may have existed before
      the advent of multicellularity. Our study also ascribes a novel function for the
      B. hominis central vacuole in apoptosis; it acts as a repository where apoptotic
      bodies are stored before being released into the extracellular space.

PMID- 11578088
TI  - Light microscopical structure and ultrastructure of a Besnoitia sp. in the
      naturally infected lizard Ameiva ameiva (Teiidae) from north Brazil, and in
      experimentally infected mice.
AB  - A Besnoitia species of the teiid lizard Ameiva ameiva (L.), from north Brazil was
      established in laboratory mice and hamster by the intraperitoneal inoculation of
      bradyzoites in the tissue cysts. In the lizards all the cyst wall layers were
      closely apposed. In the mice the layers of the wall were distinguishable, and
      ultrastructurally the inner cytoplasmic layer contained either a tight network of
      endoplasmic reticulum or packed mitochondria or both. These components were less
      frequent or sparse in the inner cytoplasmic layer of cysts in the lizard. The
      only animals available for experiments in attempts to indicate the definitive
      host of the parasite were 3 kittens of the domestic cat and a juvenile specimen
      of the snake Boa constrictor raised in captivity. No evidence of infection could
      be detected in these animals after feeding them with the tissues of mice
      harbouring cysts with very large number of bradyzoites.

PMID- 11578089
TI  - Long-term dynamics of Ligula intestinalis and roach Rutilus rutilus: a study of
      three epizootic cycles over thirty-one years.
AB  - Data are presented on 2 full epizootic cycles and the start of a third of Ligula
      intestinalis in roach Rutilus rutilus in a small lake, and the relationships of
      these cycles to the densities of rudd, Scardinius erythrophthalmus, and Great
      Crested Grebes, Podiceps cristatus, over 31 years. The parasite was introduced to
      the lake by P. cristatus in 1973 at a time when the roach population had
      increased in response to eutrophication to a level at which individual fish
      growth was stunted and the hithero dominant rudd population had declined in
      numbers as a consequence of inter-specific competition with roach. Ligula
      prevalence peaked at 28% in only 2 years: thereafter parasite-induced host
      mortality caused a decline in the roach population, releasing fish from stunting
      and allowing the rudd population to recover. The consequent improved growth of
      roach individuals and their short life-span reduced Ligula transmission rates and
      prevalence levels declined to approximately 1% although Ligula nevertheless
      persisted for a further 10 years. Following a massive winter-kill of the fish
      populations in 1984-1985, fish and Ligula numbers declined to barely detectable
      levels and the parasite disappeared from samples. Rudd recovered first, then
      roach and interspecific competition again led to a decline in rudd numbers. This
      increase in roach numbers led to a decrease in roach growth rates, which
      coincided with the re-colonization of the lake by Ligula. This second epizootic
      of Ligula peaked within 2 years in 1991-1992, when up to 78% of roach were
      infected with a maximum abundance of 2.2 parasites and intensity of 21 parasites.
      Heavy parasite-induced mortality of roach led to a decline in numbers, an
      improvement in individual growth rate and a reduction of Ligula transmission
      rates such that the epizootic died out in 1996. Similar conditions of roach
      numbers and growth prevailed at the start of a third cycle in 1998. The course of
      events over the second cycle was so similar to that of the first that it confirms
      the interpretations of that cycle. Comparison with other localities shows that
      epizootics of Ligula always coincide with rapid increases in roach numbers, for
      whatever cause, and stunted growth, which together attract piscivorous birds. At
      the start of a cycle Ligula is a major determinant of the population dynamics of
      the roach, but at the end of the cycle the fish population dynamics determine
      those of the parasite. The cycles are not regulated and the roach-Ligula system
      is inherently unstable.

PMID- 11578090
TI  - The interaction between the gelatin-binding domain of fibronectin and the
      attachment of Pasteuria penetrans endospores to nematode cuticle.
AB  - Pasteuria penetrans is a Gram-positive endospore-producing bacterium that is a
      parasite of root-knot nematodes. Attachment of endospores to the cuticle of the
      nematode is the first stage in the infection process. Western blot analysis with
      monoclonal and polyclonal antibodies that recognize the 30 kDa heparin-binding
      domain (HBD) and the 45 kDa gelatin-binding domain (GBD) fragments of human
      fibronectin (Fn) revealed a series of polypeptides of approximately 40, 45 and 55
      kDa present in crude cuticle extracts of Meloidogyne javanica 2nd-stage
      juveniles. The results suggest that the structure of the nematode fibronectin is
      different to the fibronectins so far characterized. Pre-treatment of endospores
      of Pasteuria with either the HBD or the GBD was found to inhibit binding to the
      nematode cuticle. The larger GBD fragment was the most effective at blocking
      adhesion. Pre-treatment of the GBD fragment with gelatin prevented the GBD
      fragment from inhibiting endospore attachment to the nematode cuticle.

PMID- 11578091
TI  - Cloning and characterization of a muscle isoform of a Na,K-ATPase alpha subunit
      (SNaK1) from Schistosoma mansoni.
AB  - A cDNA encoding a Na,K-ATPase alpha subunit homologue, designated SNaK1, was
      isolated from an adult cDNA library of Schistosoma mansoni. The 3.8 kb DNA
      contained a 3021 bp open reading frame potentially encoding a 1,007 amino acid
      protein that had an Mr of 111,817 and a pl of 5.48. Homology searches for SNaK1
      revealed approximately 70% sequence identity with a variety of Na, K-ATPases from
      evolutionarily diverse organisms. SNaK1 is predicted to contain 10 transmembrane
      regions typical of this protein family as well as other conserved domains, such
      as the phosphorylation site and ATP binding domain. Antibodies raised against an
      amino terminal peptide detected the protein in membrane preparations of eggs,
      cercariae and adult males and females, suggesting a general role for SNaK1. The
      mobility of the protein differed in various life-stages suggestive of post
      transcriptional or post-translational modification. Immunolocalization of SNaK1
      in sections of adult worms using epifluorescence and electron microscopy,
      revealed antibody labelling in the subtegumental and peripheral layers. Strong
      staining was discernible in the peripheral muscle band indicating that SNaK1
      plays a central role in muscle contraction in adult parasites and may be the
      primary target of ouabain action. Staining was also detected in the secretory
      bodies in sections of ducts in this region and over the RER of the presumed
      gastrodermis. Immunogold labelling was also localized over neuronal vesicles in
      axons associated with the peripheral muscle layer.

PMID- 11578092
TI  - In vitro cultivation of anisakis simplex: pepsin increases survival and moulting
      from fourth larval to adult stage.
AB  - This paper describes the in vitro cultivation of the 3rd-larval stage (L3) of
      Anisakis simplex to adulthood in a much simpler and easier to prepare medium than
      those described to date. The adult males obtained are between 3.8 and 6.5 cm long
      and the females between 4.5 and 8.0 cm. Some individually cultivated females laid
      eggs which had an average size of 44.4 x 50.5 microm. The culture conditions were
      as follows: medium RPMI-1640 supplemented with 20% heat-inactivated fetal bovine
      serum and 1% commercial pepsin, at pH 4.0 and a temperature of 37 degrees C, and
      in air atmosphere with 5% CO2. The pepsin was found to be the key to the success
      of the culture. The average survival of the worms in the culture increased from
      50 to 88 days, due to the fact that the survival of the adults practically
      doubled (increasing by 1.9 times). Furthermore, the number of worms that
      completed the 4th moulting (M4) increased by 4.2 times, from 22.9 to 95.6%. This
      culture medium may facilitate, due to its simplicity, the study of anisakids, or
      at least of A. simplex, constituting another step towards achieving a complete in
      vitro life-cycle for these parasites.

PMID- 11578093
TI  - Identification of some heat-induced genes of Trichinella spiralis.
AB  - Three heat-induced genes of the infective-stage larvae of Trichinella spiralis
      were successfully identified by the suppression subtractive hybridization (SSH)
      technique. As indicated by reverse Northern blotting, 19 of 25 clones were scored
      as differentially transcribed in the heat-shocked infective-stage larvae. The
      sequencing data showed the presence of 12 different genes. Three were homologous
      to histone H3, histone H2B and translationally controlled tumour protein (TCTP).
      A 0.6 kb cDNA of histone H3 was generated by the RACE method and sequenced. It
      contained an open reading frame of 136 amino acids that demonstrated 94% identity
      with genes from Drosophila hydei. Semi-quantitative RT-PCR indicated that after
      heat-shock treatment, the expression levels of histone H3, histone H2B and TCTP
      increased 4.8, 27 and 5.7-fold, respectively. Northern analysis confirmed the
      upregulation of histone H3, histone H2B and TCTP transcripts. The upregulation of
      these genes during stress conditions has not been reported in parasitic
      organisms. The stress proteins may play an active role to sustain the parasite
      after exposure to hostile host factors.

PMID- 11578094
TI  - DNA-binding activity in the excretory-secretory products of Trichinella
      pseudospiralis (Nematoda: Trichinelloidea).
AB  - A novel DNA-binding peptide of Mr approximately 30 kDa was documented for the
      first time in the excretory-secretory (E-S) products of the infective-stage
      larvae of Trichinella pseudospiralis. Larvae recovered from muscles of infected
      mice were maintained for 48 h in DMEM medium. E-S products of worms extracted
      from the medium were analysed for DNA-binding activity by the electrophoretic
      mobility shift assay (EMSA). Multiple DNA-protein complexes were detected. A
      comparison of the Mr of proteins in the complexes indicated that they could bind
      to the target DNA as a dimer, tetramer or multiples of tetramers. Site selection
      and competition analysis showed that the binding has a low specificity. A (G/C
      rich)-gap-(G/T-rich)-DNA sequence pattern was extracted from a pool of degenerate
      PCR fragments binding to the E-S products. Results of immunoprecipitation and
      electrophoretic mobility supershift assay confirmed the authenticity of the DNA
      binding protein as an E-S product.

PMID- 11578095
TI  - A novel method for the isolation of gastro-intestinal nematode eggs that allows
      automated analysis of digital images of egg preparations and high throughput
      screening.
AB  - A simple and robust method for the isolation of gastro-intestinal nematode eggs
      from faeces is described that uses both salt- and sugar solutions for flotation.
      Application of this 'salt-sugar' isolation method to large numbers of faecal
      samples of adult dairy cows indicates a 3- or 4-fold reduction in the proportion
      of e.p.g.-negative cows relative to studies that used other techniques for egg
      isolation. The procedure detects more eggs than the Wisconsin flotation method in
      replicate samples and in spiked egg-free faeces. The number of recovered eggs in
      spiked faecal samples is linear over a range of egg concentrations, and the
      transparent faecal preparations that result from the protocol can be stored as
      digital images which can be used as input for an efficient automated egg-counting
      procedure. The increased rate of processing of faeces combined with the large
      reduction of the percentage of e.p.g.-negative cows allows more accurate analysis
      of large numbers of adult or resistant animals for studies of nematode
      parasitism.

PMID- 11578096
TI  - The effect of dietary carbohydrates with different digestibility on the
      populations of Oesophagostomum dentatum in the intestinal tract of pigs.
AB  - An experiment was undertaken to study the effect of dietary carbohydrates with
      different digestibility on the populations of Oesophagostomum dentatum in the
      intestinal tract of pigs. Sixty-four worm-free pigs from a specific pathogen-free
      farm were randomly divided into 8 equal groups. The animals in 4 groups were
      assigned to a diet with partially undegradable carbohydrates (diet 1), while the
      pigs in the 4 remaining groups were given a diet with fermentable carbohydrates
      (diet 2). Diet 1 was comprised of barley flour, oat husk meal, soybean meal,
      vitamins and minerals and diet 2 of barley flour, inulin and sugar beet fibre,
      soybean meal, vitamins and minerals. The pigs in 6 of the groups (n = 48) were
      inoculated with 6,000 infective larvae of O. dentatum. To determine O. dentatum
      populations at the early stage of infection, 16 pigs were slaughtered 3 weeks
      p.i., while the remaining 4 groups continued on the diets for a further 9 weeks
      after which they were slaughtered. In a diet cross-over experiment 6 weeks after
      inoculation, 8 pigs changed from diet 1 to diet 2 (diet 1 > diet 2), and 8 pigs
      from diet 2 to diet 1 (diet 2 > diet 1). The results showed that partially
      undegradable carbohydrates provided favourable conditions not only for parasite
      establishment and sustainability, but also for already established O. dentatum
      infection while, in contrast, the diet composed of highly degradable
      carbohydrates decreased worm establishment, size and female fecundity. The
      implications for pastured pigs or pigs fed different complex carbohydrate diets
      is discussed.

PMID- 11578097
TI  - Chickens and pigs as transport hosts for Ascaris, Trichuris and Oesophagostomum
      eggs.
AB  - Ten chickens and 2 pigs were fed non-embryonated eggs of Ascaris suum, Trichuris
      suis and Oesophagostomum dentatum. Each chicken was fed approximately 15,000 eggs
      of each parasite species while approximately 300,000 eggs were given to each of
      the pigs. After passage in chickens 8.3% of O. dentatum eggs were recovered in
      faeces compared to 61.1% and 38.4%, 49.1% and 30.3%, 41.6% of A. suum and T. suis
      eggs, respectively. After passage in pigs the percentages were respectively.
      After embryonation in the laboratory, 1,000 eggs of each parasite species having
      passed through chickens or pigs or having been kept in the laboratory as controls
      were fed to groups of 6 pigs to check the infectivity. The number of A. suum
      recovered from pigs was similar in the 3 groups with 34.0, 52.8 and 41.8%,
      respectively. The recovery of T. suis in the pig passage group was 54.0% which
      was significantly lower than the recovery in the chicken passage group (81.8%)
      and the laboratory group (88.0%). The number of O. dentatum recovered was not
      significantly different among the 3 experimental groups, the percentage recovery
      being 30.5, 9.2 and 28.5%, respectively. One explanation for the lower
      infectivity of T. suis in the pig passage group may be that the eggs have been
      sublethally damaged through their passage. The results demonstrate that chickens
      and pigs can act as transport hosts for A. suum, T. suis and O. dentatum, and it
      is highly probable that these domestic animals are able to act also as transport
      hosts for the human parasite equivalents. This will have important consequences
      for the environmental and behavioural strategies in human helminth control

PMID- 11578098
TI  - The challenge of gene therapy and DNA delivery.
AB  - It is 10 years since the first gene therapeutic was administered to patients.
      Since that time approximately 3500 patients have been treated and although some
      evidence of gene transfer has been seen it has generally been inadequate for a
      meaningful clinical response. The major challenges have been delivery of DNA to
      the target cells and duration of expression. A variety of gene transfer systems
      have been evaluated and these are summarized with their advantages and
      disadvantages. Encouraging data have been obtained recently by a number of
      workers and there is some optimism that the enormous potential of gene therapy
      will be realized in the second decade of its development.

PMID- 11578099
TI  - New strategies for polymer development in pharmaceutical science--a short review.
AB  - We are developing synthetic polymers for pharmaceutical and medical applications.
      These applications can be broadly grouped on how the polymer will be utilized
      e.g. material, excipient or molecule. Our focus is to develop polymers with more
      defined structures that are based on biological, physicochemical and/or materials
      criteria. Strategies are being developed to more efficiently optimize structure
      property correlations during preclinical development. We describe two examples of
      our research on pharmaceutical polymer development: narrow molecular weight
      distribution (MWD) homopolymeric precursors which can be functionalized to give
      families of narrow MWD homo- and co-polymers, and hydrolytically degradable
      polymers.

PMID- 11578100
TI  - Oral sustained delivery of theophylline from thermally reversible xyloglucan gels
      in rabbits.
AB  - Thermally reversible gels formed in-situ following the oral administration of
      dilute aqueous solutions of an enzyme-degraded xyloglucan to rabbits were
      evaluated as sustained-release vehicles for the delivery of theophylline. In
      vitro release of theophylline from gels formed by warming xyloglucan sols (0.5,
      1.0 and 1.5% w/w) to 37 degrees C followed root-time kinetics over a period of 4
      h. Gels formed after oral administration to rabbits of chilled 1.5% w/w aqueous
      solutions of xyloglucan containing dissolved drug showed sustained-release
      characteristics with a maximum plasma concentration at 4.5 h. The theophylline
      bioavailability from a 1.5% w/w xyloglucan gel was 1.7-2.5 times that of
      commercial oral sustained-release liquid dosage forms containing an identical
      theophylline concentration. It was concluded that dilute solutions of the enzyme
      degraded xyloglucan had suitable rheological properties and in-situ gelling
      characteristics for use as sustained-release vehicles for oral drug delivery. The
      in-vivo release characteristics of theophylline in a rabbit model suggested the
      potential for the use of these vehicles in humans for the oral delivery of this
      drug.

PMID- 11578101
TI  - The powder flow and compact mechanical properties of two recently developed
      matrix-forming polymers.
AB  - The powder flow and compact mechanical properties of two recently developed
      matrix-forming polymers were determined. The polymers are cross-linked high
      amylose starch (Contramid) and poly(acrylic acid) (Carbopol EX507), and their
      properties were compared with those of two established matrix-forming polymers,
      hydroxypropyl methylcellulose (Methocel K100LV) and hydroxypropyl cellulose
      (Klucel EXF). The particle morphology, size distribution and true density of the
      four materials were quite different and they exhibited measurable performance
      differences with respect to powder flow, compact ductility, compact elasticity
      and compact tensile strength. Recommendations for formulating solid dosage forms
      with each of these excipients were made, based on a consideration of their
      physical properties and their anticipated processing performance.

PMID- 11578102
TI  - Effectiveness of repeated administration of a new oral naltrexone controlled
      release system on morphine analgesia.
AB  - Naltrexone hydrochloride, an opioid antagonist used as an adjunct to the
      maintenance of the opioid-free state for detoxified individuals, was introduced
      into the polymeric structure of Eudragit L30D, an anionic copolymer based on
      polymethacrylic acid and ethylacrylate. From the results of a preclinical study,
      this complexation technique can be considered as a useful tool in the design of
      oral controlled-release systems (naltrexone-Eudragit L) capable of inducing long
      lasting effects in-vivo. The biopharmaceutical characterization of the naltrexone
      Eudragit L complex in comparison with naltrexone hydrochloride using the mouse
      hot-plate model has been previously carried out. The results showed a longer
      effect, an enhancement of 23.47% of the area under the curve of the inhibition of
      analgesic activity vs time, and a delay of 51.80% in the t1/2 value induced by
      the complex, compared with those induced by conventional naltrexone. In this
      study, a regimen of chronic administration of naltrexone-Eudragit L was
      established. Thus, in an 8-day treatment (4 doses in alternate days) this oral
      controlled-release system effectively antagonized the analgesic effect of
      morphine for 8 h, whereas naltrexone hydrochloride has to be administered over 16
      days (8 doses in alternate days) to induce the same effect. In the 16-day
      schedule the complex-induced antagonism lasted over 14 h after administration.

PMID- 11578103
TI  - Colon-specific delivery of budesonide from microencapsulated cellulosic cores:
      evaluation of the efficacy against colonic inflammation in rats.
AB  - Budesonide (BDS) is a potent corticosteroid that has important implications in
      the pharmacotherapy of inflammatory bowel disease, especially in the treatment of
      ulcerative colitis and Crohn's disease. BDS is available on the market in the
      form of enteric-coated preparations. However these products, similar to other
      available site-specific dosage forms, are not sufficiently selective to treat
      colonic inflammatory bowel disease. The objective of this study was to evaluate
      the efficacy of a new microparticulate system containing BDS, to treat
      experimentally induced colitis in rats. This microparticulate system consisted of
      BDS-containing hydrophobic cores, microencapsulated within an enteric polymer,
      which solubilizes at above pH 7, thus combining pH-sensitive and controlled
      release properties. Colonic injury and inflammation were assessed by measuring
      colon/bodyweight ratio, myeloperoxidase (MPO) activity, and by scoring
      macroscopic and histological damage in colitic rats. Rats were treated orally
      with BDS, included in the developed system, once a day for 4 days after the
      induction of inflammation. A BDS suspension and BDS-containing enteric
      microparticles were included as control formulations in the experimental design.
      The administration of the new BDS delivery system significantly reduced the
      colon/bodyweight ratio compared with the administration of control formulations.
      Similarly, MPO activity and macroscopic and histological damage of the inflamed
      colonic segments decreased significantly when the BDS formulation was
      administered, compared with the results obtained after oral administration of the
      drug suspension. There were no significant differences, however, when the new
      treatment was compared with the control formulation consisting of simple enteric
      microparticles.

PMID- 11578104
TI  - Improved activity and stability of lysozyme at the water/CH2Cl2 interface: enzyme
      unfolding and aggregation and its prevention by polyols.
AB  - Protein inactivation and aggregation at the water/CH2Cl2 interface is one of the
      most detrimental events hindering the encapsulation of structurally unperturbed
      proteins into poly(lactide-co-glycolide) (PLG) microspheres for their clinical
      application as sustained release dosage forms. We have investigated the
      inactivation and aggregation of the model protein hen egg-white lysozyme at this
      interface and devised methods to prevent both events. When lysozyme was exposed
      to a large water/CH2Cl2 interface achieved by homogenization, lysozyme
      aggregation occurred. Fourier-transform infrared (FTIR) spectroscopic data
      demonstrated that the aggregates formed contained intermolecular beta-sheets. The
      aggregates were of a noncovalent nature because they slowly dissolved in D2O and
      the IR spectral bands typical for the intermolecular beta-sheets disappeared at
      approximately 1617 and 1690 cm(-1). The observed loss in specific enzyme activity
      of soluble lysozyme was caused by the irreversible formation of an unfolded
      lysozyme species, which was found to be monomeric, and was able to leave the
      water/CH2Cl2 interface and accumulate in the aqueous phase. Polyols were, in a
      concentration dependent fashion, efficient in ameliorating lysozyme unfolding and
      aggregation. However, prevention of lysozyme aggregation and activity loss in the
      various samples were unrelated. Thus, polyols must work by more than one
      mechanism preventing the two events. For the first time, an excipient effect on
      the conformational stability of lysozyme has been excluded from contributing to
      the prevention of lysozyme unfolding and aggregation.

PMID- 11578105
TI  - Iontophoretic pulsatile transdermal delivery of human parathyroid hormone (1-34).
AB  - Iontophoretic pulsatile transdermal delivery of hPTH(1-34) was examined in
      Sprague-Dawley (SD) rats, hairless rats and beagle dogs. Application for 60 min
      (200 microg; 0.1 mA cm(-2)) showed current-responsive increases in serum hPTH(1
      34) levels in all the animals. In SD rats, the area under the curves of serum
      hPTH(1-34) levels (AUCs) were proportional to the doses (40, 120, 200, 400 and
      1000 microg) and current densities (0.05, 0.1 and 0.15mA cm(-2)) applied. The
      absorption rates per 200-microg dose, calculated by a deconvolution method, were
      6.7, 2.4 and 3.7 microg h(-1) for SD rats, hairless rats and beagle dogs,
      respectively. These values correlated well with the ratios of the skin porosity
      to the dermal thickness reported for these animals, which are believed to
      represent the reciprocal of the electrical resistance of the aqueous channels
      formed by the hair follicles. From this correlation, we suggested that absorption
      of hPTH(1-34) occurs mainly via the hair-follicle route, and that the absorption
      rate in man might be intermediate between those in hairless rats and beagle dogs.
      Three-fold repetitions of 30 min current with various rest intervals produced
      current-responsive triple pulses in serum hPTH(1-34) levels in SD rats. Seven
      fold repetitions of current also produced similar current-responsive pulsatile
      serum hPTH(1-34) levels. However, peak serum hPTH(1-34) levels tended to decrease
      gradually after the fourth current application, possibly due to consumption of
      the electrodes, suggesting that three-fold repetitions of current might be
      optimal. These findings suggest that this iontophoretic administration system
      could create a repeated-pulsatile pattern of serum hPTH(1-34) levels without the
      necessity for frequent injections, and may be useful for the treatment of
      osteoporosis with hPTH(1-34).

PMID- 11578106
TI  - Pharmacokinetic-pharmacodynamic modelling of human insulin: validity of
      pharmacological availability as a substitute for extent of bioavailability.
AB  - A method for assessing the extent of bioavailability (EBA) of human insulin from
      pharmacological data was determined. The time course governing increases in the
      plasma concentration of immuno-reactive insulin (IRI), as well as its
      pharmacological effects (glucodynamics), was determined after the intravascular
      administration of varying doses of human insulin. Pharmacokinetic (PK),
      pharmacodynamic (PD), and link models were constructed to elucidate the
      quantitative relationship between plasma IRI levels and pharmacological effects.
      After extravascular administration of the test formulation, only the time course
      governing the observed pharmacological effects was determined. The
      pharmacological data was translated into theoretical plasma concentration data,
      using the PK-PD model. Following this, the area under the theoretical plasma
      concentration-time curve (AUC) of the test formulation was calculated. The EBA
      was then estimated against a reference (intravascular) formulation, using a
      conventional equation. Since the pharmacological effects of insulin were observed
      to be highly dosing-rate-dependent, the PD model used in this study was modified
      to apply over a wide range of infusion rates. The results of the PK-PD analysis
      indicate that the doses administered can be accurately predicted from
      pharmacological data. To validate this method, the EBAs of controlled release
      formulations (the Osmotic Mini Pumps) of insulin, subcutaneously administered to
      the rat, were estimated. The EBA values obtained (92-96%) fell within a
      reasonable range. The area under the effect-time curves (AUE) obtained following
      subcutaneous applications of the Osmotic Mini Pump were calculated in a model
      independent manner, in addition to pharmacological availabilities (PA), which
      were estimated against the reference (intravascular) formulations. The estimated
      PA values varied from 312% to 78%, in accordance with the intravascular input
      rates of the reference formulations. This indicates that PA should not be used as
      a substitute for EBA, unless data involving similar intravascular dosing rates to
      that of the reference formulations is available.

PMID- 11578107
TI  - Pharmacokinetic study on gastrointestinal absorption of insulinomimetic vanadyl
      complexes in rats by ESR spectroscopy.
AB  - Recently, we have shown that oral administrations of vanadyl (+4 oxidation state
      of vanadium) complexes normalize the blood glucose level of streptozotocin
      induced diabetic rats (STZ-rats). To develop clinically useful insulin-mimetic
      vanadyl complexes, clarification of the pharmacokinetic features of vanadyl
      compounds is essential. First, we investigated the absorption processes of three
      compounds, an ionic form of vanadyl sulfate (VS) and the complex forms of
      bis(picolinato)oxovanadium(IV) (VO(pic)2) and bis(6
      methylpicolinato)oxovanadium(IV) (VO(6mpa)2), from the gastrointestinal tract of
      healthy rats. The concentration curves of paramagnetic vanadyl species in the
      blood of rats after oral administration of these compounds, as monitored by X
      band electron spin resonance (ESR) spectroscopy, exhibited biphasic increasing
      patterns, indicating that these compounds were absorbed from more than two sites
      in the gastrointestinal tract. The bioavailability of the compounds was enhanced
      in the following order on both oral and intraperitoneal administration: VO(6mpa)2
      > VO(pic)2 > VS. In addition, bioavailability of the VO(6mpa)2 on ileal
      administration was enhanced compared with that using other administration sites
      such as the stomach and jejunum, and resulted in an enhancement about 1.8 fold
      that compared with oral administration. On the basis of these results, we
      concluded that the bioavailability of the complex is enhanced most effectively by
      delivery of the VO(6mpa)2 complex to the ileum.

PMID- 11578108
TI  - Hexarelin--evaluation of factors influencing oral bioavailability and ways to
      improve absorption.
AB  - Hexarelin, a hexapeptide with growth hormone-releasing activity, has been found
      in man to have a biological bioavailability (estimated from growth hormone
      levels) of 0.3+/-0.1% after oral administration. The cause of the low oral
      efficacy of hexarelin and means of improving its absorption have been evaluated.
      It was found that hexarelin was degraded in the presence of the contents of the
      intestine. The metabolite was identified as hexarelin deamidated at the lysine
      residue. The degradation of hexarelin in the contents of rat ileum was inhibited
      by the addition of chymostatin, Pefabloc SC, EDTA, and EGTA. Furthermore, the
      presence of pancreatic proteases from pancrease substitute drugs caused a
      degradation of hexarelin that could be inhibited by the addition of Pefabloc SC.
      The same hexarelin metabolite that was found with the contents of rat ileum was
      found in the presence of human, porcine and bovine trypsin. Hexarelin
      permeability across rat ileum and in Caco-2 cell monolayers was low. An increase
      in hexarelin permeability was observed in the presence of different permeability
      enhancing agents.

PMID- 11578109
TI  - The use of polymeric solid phase extraction and HPLC analysis for the
      determination of ranitidine in routine plasma samples obtained from paediatric
      patients.
AB  - A sensitive HPLC method for the determination of ranitidine in small-volume (0.5
      mL) paediatric plasma samples is described. Plasma samples were extracted using a
      simple, rapid solid phase extraction (SPE) technique developed using disposable
      copolymer packed SPE cartridges. Chromatographic separation was achieved by
      reverse-phase HPLC with isocratic elution using a microBondapak C18 column and a
      phosphate buffer (10 mM, pH 3.75)-acetonitrile (87:13 v/v) mobile phase with UV
      detection at 313 nm. The HPLC system exhibited linearity in the range 8-800 ng
      mL(-1). Intraday % CV and % bias values were in the range 1.28-8.09% (% bias 
      4.33 to -0.87) and interday % CV and % bias values were in the range 0.73-15.28%
      (% bias -1.80 to + 1.65). The limits of detection and quantitation obtained were
      2 ng mL(-1) and 8 ng mL(-1), respectively, and ranitidine extraction recoveries
      from plasma ranged from 92.30 to 103.88%. In this study, the developed HPLC and
      SPE methodologies have been successfully applied to the determination of
      ranitidine concentrations in 68 paediatric plasma samples. The sampled population
      was drawn from patients already receiving the study drug therapeutically.
      Patients recruited had received ranitidine by two main routes - oral and
      intravenous. The plasma concentrations of ranitidine encountered in paediatric
      samples following oral or intravenous administration of a range of prescribed
      doses are presented graphically. These profiles are based on analysis of the
      first 68 plasma samples obtained from the first 35 patients recruited to the
      study receiving ranitidine by the oral or intravenous route.

PMID- 11578110
TI  - Monoamine oxidase inhibitory activity of some Hypericum species native to South
      Brazil.
AB  - The total methanol crude extracts and petroleum ether, chloroform, and methanol
      fractions obtained from Hypericum species, H. caprifoliatum, H. carinatum, H.
      connatum, H. cordatum, H. myrianthum, H. piriai, H. polyanthemum and H.
      brasiliense, all native to South Brazil, were assayed for monoamine oxidase A
      (MAO A) and MAO B inhibitory activity in rat brain mitochondrial preparations at
      concentrations ranging from 1 to 20microg mL(-1). Three benzopyrans, HP1 (6
      isobutyryl-5,7-dimethoxy-2,2-dimethylbenzopyran), HP2 (7-hydroxy-6-isobutyryl-5
      methoxy-2,2-dimethylbenzopyran) and HP3 (5-hydroxy-6-isobutyryl-7-methoxy
      2,2dimethylbenzopyran) isolated from H. polyanthemum were also tested at maximal
      concentrations of 150, 150 and 75/microM, respectively. The lipophilic extracts
      of H. polyanthemum, H. caprifoliatum and H. piriai displayed MAO A inhibitory
      activity greater than 50%. Among the benzopyrans, only HP3 showed significant
      activity, with an IC50 value of 22 microM. The total methanol crude extracts of
      aerial parts from H. carinatum, H. connatum, H. cordatum, H. polyanthemum and H.
      piriai were evaluated for antidepressant activity in the Porsolt's forced
      swimming test in Wistar rats (270 mg kg(-1) day(-1); i.p); however, none of them
      showed activity.

PMID- 11578111
TI  - Inhibition of serum angiotensin-converting enzyme in rabbits after intravenous
      administration of enalaprilat-loaded intact erythrocytes.
AB  - Encapsulation of drugs in intact erythrocytes, because of the profound
      characteristics of these natural microspheres, has gained considerable attention
      in recent years. In this study, the inhibition time courses of serum angiotensin
      converting enzyme (ACE) activity after intravenous administration of enalaprilat
      encapsulated in intact erythrocytes was evaluated and compared with free drug, in
      a rabbit model. Three groups of animals each received free drug, drug-loaded
      erythrocytes or sham-encapsulated erythrocytes. Serum ACE activity was determined
      in each case using the synthetic substrate hippuryl-histidyl-leucine and
      quantitation of the hippuric acid released by a developed and validated HPLC
      method. The serum ACE inhibition profiles in the three groups showed that the
      encapsulated drug inhibited the serum ACE more slowly, more efficiently, over a
      considerably longer time and in a more reproducible manner, than the free drug or
      sham-encapsulated erythrocytes. We conclude that the erythrocytes can serve as
      efficacious slow-release drug carriers for enalaprilat in circulation.

PMID- 11578112
TI  - In-vitro and in-vivo immunomodulatory effects of syringin.
AB  - Syringin was found to possess immunomodulatory activity by which it inhibited the
      in-vitro immunohaemolysis of antibody-coated sheep erythrocytes by guinea-pig
      serum through suppression of C3-convertase of the classical complement. In this
      study, we examined its in-vitro and in-vivo activity on tumour necrosis factor
      (TNF)-alpha and nitric oxide (NO) production, CD4+ T cell and CD8+ cytotoxic T
      cell (CTLL-2) proliferation, and croton oil-, arachidonic acid- and fluorescein
      isothiocynate (FITC)-induced mouse ear oedema model. Syringin significantly
      inhibited both TNF-alpha production from lipopolysaccharide (LPS)-stimulated
      RAW264.7 cells and CD8+ T cell (CTLL-2) proliferation in a dose-dependent manner,
      whereas neither NO production nor CD4+ T cell proliferation were blocked even by
      high concentrations of syringin. In the invivo experiments, syringin also
      significantly suppressed FITC-induced ear oedema in mice but not the ear oedema
      induced by croton or arachidonic acid. These results suggest that syringin may be
      implicated as an immunomodulator having an anti-allergic effect rather than an
      anti-inflammatory effect. The anti-allergic effect of syringin seems to be due,
      in part, to inhibition of TNF-alpha production and cytotoxic T cell
      proliferation.

PMID- 11578113
TI  - Inhibition of prostalglandin E2 production by 2'-hydoxychalcone derivatives and
      the mechanism of action.
AB  - The effects of 14 synthetic 2'-hydroxychalcone derivatives on prostaglandin E2
      (PGE2) production in rat peritoneal macrophages stimulated by the protein kinase
      C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), were examined to clarify
      the structure-activity relationship. 2',4-Dihydroxy-4'-methoxychalcone (compound
      3), 2',4-dihydroxy-6'-methoxychalcone (compound 8) and 2'-hydroxy-4'
      methoxychalcone (compound 9) suppressed PGE2 production more potently than the
      other compounds. The IC50 (50% Inhibitory concentration) value for compounds 3, 8
      and 9 was calculated to be 3 microM. The activity of cyclooxygenase (COX)-1 was
      inhibited slightly by compound 9, but that of COX-2 was not inhibited. At
      concentrations that inhibited the production of PGE2, compound 9 had no effect on
      the release of radioactivity from [3H]arachidonic acid-labelled macrophages
      stimulated by TPA. Western-blot analysis revealed that the induction of COX-2
      protein by TPA was inhibited by compound 9 in parallel with the inhibition of
      PGE2 production. Compounds 3 and 8 had similar effects. These findings suggest
      that 4'-methoxyl and 6'-methoxyl groups are required for the expression of more
      potent inhibitory activity against PGE2 production, and that the inhibition of
      PGE2 production by these 2'-hydroxychalcone derivatives is due to the inhibition
      of TPA-induced COX-2 protein expression.

PMID- 11578115
TI  - A theoretical model of intracellular devitrification.
AB  - Devitrification of the intracellular solution can cause significant damage during
      warming of cells cryopreserved by freezing or vitrification. Whereas previous
      theoretical investigations of devitrification have not considered the effect of
      cell dehydration on intracellular ice formation, a new model which couples
      membrane-limited water transport equations, classical nucleation theory, and
      diffusion-limited crystal growth theory is presented. The model was used to
      explore the role of cell dehydration in devitrification of human keratinocytes
      frozen in the presence of glycerol. Numerical simulations demonstrated that water
      transport during cooling affects subsequent intracellular ice formation during
      warming, correctly predicting observations that critical warming rate increases
      with increasing cooling rate. However, for cells with a membrane transport
      activation energy less than approximately 50 kJ/mol, devitrification was also
      affected by cell dehydration during warming, leading to a reversal of the
      relationship between cooling rate and critical warming rate. Thus, for low
      warming rates (less than 10 degrees C/min for keratinocytes), the size and total
      volume fraction of intracellular ice crystals forming during warming decreased
      with decreasing warming rate, and the critical warming rate decreased with
      increasing cooling rate. The effects of water transport on the kinetics of
      intracellular nucleation and crystal growth were elucidated by comparison of
      simulations of cell warming with simulations of devitrification in H(2)O-NaCl
      glycerol droplets of constant size and composition. These studies showed that the
      rate of intracellular nucleation was less sensitive to cell dehydration than was
      the crystal growth rate. The theoretical methods presented may be of use for the
      design and optimization of freeze-thaw protocols.

PMID- 11578116
TI  - Experimental studies of ice nucleation in an Antarctic springtail (Collembola,
      Isotomidae).
AB  - Ice nucleation was studied in field-fresh and acclimated (4 degrees C without
      food for 11-20 days) samples of the springtail Cryptopygus antarcticus Willem
      (Collembola, Isotomidae) at Rothera Research Station, Adelaide Island on the
      Antarctic Peninsula. Ice nucleator activity (INA) was measured by a freezing
      droplet technique in addition to supercooling point (SCP) profiles and polyol,
      sugar, and water contents. Field and acclimated samples showed bimodal SCP
      distributions with a distinct high group (HG; mean SCP -8 to -10 degrees C) and
      low group (LG: mean SCP -23 to -25 degrees C), which were significantly
      different. Acclimation at 4 degrees C increased the proportion of individuals in
      the LG relative to that in the HG without significant effects on the mean SCP of
      both groups. INA of the HG was significantly greater than that of the LG, and
      acclimation further reduced the INA of the LG. The number of active ice nucleator
      agents (INAs) calculated for the HG of field samples increased by 23-100 times
      over the temperature range -5 to -8 degrees C compared to only 7 times for the LG
      over the same range. These differences were accentuated in the acclimation
      experiments. Glucose and galactose were the main carbohydrates in both field and
      acclimated springtails, with the latter compound occurring in almost twice the
      concentration in the LG compared with that in the HG. Acclimation reduced the
      concentration of both compounds (glucose by 77% and galactose by 54%), whereas
      water content increased significantly. Digestion of food may have continued
      during acclimation at 4 degrees C, which could reduce the LG INA. Lowering of
      temperature over time is more likely to elicit a cold hardening response than
      constant temperature acclimation. INA numbers calculated at the nucleation
      temperatures for C. antarcticus samples were higher in the LG than in the HG.
      However, inactivation of INAs may be a key mechanism underlying cold hardening in
      this species, either by sequestration within the cellular matrix or by being only
      seasonally active.

PMID- 11578117
TI  - Flounder antifreeze peptides increase the efficacy of cryosurgery.
AB  - Type I antifreeze protein (AFP) from the winter flounder (Pseudopleuronectes
      americanus) was used as an adjuvant to cryosurgery of subcutaneous tumors of
      Dunning AT-1 rat prostate cells grown in Copenhagen rats. The cryosurgical
      procedure was performed with a commercially available cryosurgery device (CRYO
      HIT, Galil Medical) with clinically relevant single- and double-freeze protocols.
      Injury was assessed with the alamar blue indicator of metabolic activity. The
      assay gave anomalous results when used to assess the extent of injury immediately
      following the procedure, underestimating the extent of injury. However, a double
      freeze procedure with antifreeze protein present was found to give significantly
      better ablation than a double-freeze without AFP or a single-freeze with or
      without AFP.

PMID- 11578118
TI  - Application of hypothermia to autologous stem cell purging.
AB  - Autologous stem cell transplantation is used widely after high-dose chemotherapy
      for treating hematological and other malignancies. Bone marrow harvested for
      autologous bone marrow transplantation may contain residual malignant cells even
      when the cancer is judged to be in remission. Attempts to purge marrow of its
      putative residual malignant cells may delay hemopoietic reconstitution and are of
      uncertain efficacy. In this report, we demonstrate the possibility of applying
      hypothermia to autologous stem cell purging. Using clonogenic assay, we compared
      the surviving fraction of human leukemia (HL60, K562) and human small cell lung
      cancer (H69) cell lines with that of normal human bone marrow CFU-GM and BFU-E
      cells after incubation at 4 +/- 0.1 degrees C for 24 and 48 h. Hypothermia
      decreased the surviving fraction of HL60, H69, and K562 cells. In contrast, the
      surviving fractions of stem cells were not affected by the temperature shift. The
      surviving fraction of HL60 cells at 4 degrees C cooling was significantly lower
      than that at 22 degrees C cooling. These findings suggest that in vitro
      hypothermia may selectively purge residual malignant cells in stored remission
      bone marrow and may be applicable before autologous bone marrow transplantation.
      In addition, the method is very simple and cost effective.

PMID- 11578119
TI  - Interactions among water content, rapid (nonequilibrium) cooling to -196 degrees
      C, and survival of embryonic axes of Aesculus hippocastanum L. seeds.
AB  - This study investigated the interactions among water content, rapid
      (nonequilibrium) cooling to -196 degrees C using isopentane or subcooled
      nitrogen, and survival of embryonic axes of Aesculus hippocastanum. Average
      cooling rates in either cryogen did not exceed 60 degrees C s(-1) for axes
      containing more than 1.0 g H(2)O g(-1)dw (g g(-1)). Partial dehydration below 0.5
      g gg(-1) facilitated faster cooling, averaging about 200 and 580 degrees C s(-1)
      in subcooled nitrogen and isopentane, respectively. The combination of partial
      drying and rapid cooling led to increased survival and reduced cellular damage in
      axes. Electrolyte leakage was 10-fold higher from fully hydrated axes cooled in
      either cryogen than from control axes that were not cooled. Drying of axes to 0.5
      g g(-1), reduced electrolyte leakage of cryopreserved axes to levels similar to
      those of control material. Axis survival was assayed by germination in vitro.
      Axes with water contents greater than 1.0 g g(-1), did not survive cryogenic
      cooling. Between 1.0 and 0.75 g g(-1), axes survived cryogenic exposure but
      developed abnormally. The proportion of axes developing normally after being
      cooled in isopentane increased with increasing dehydration below 0.75 g g(-1),
      reaching a maximum between 0.5 and 0.25 g g(-1) after being cooled at > or =300
      degrees C s(-1). Cooling rates attained in subcooled nitrogen did not exceed 250
      degrees C s(-1), and normal development of axes was observed only at < or =0.4 g
      g(-1). These results support the hypothesis that rapid cooling enhances the
      feasibility of cryopreservation of desiccation-sensitive embryonic axes by
      increasing the upper limit of allowable water contents and overall survival.

PMID- 11578120
TI  - Desiccation tolerance in human cells.
AB  - The ability to desiccate mammalian cells while maintaining a high degree of
      viability would have implications for many areas of biological science, including
      tissue engineering. Previously, we reported that introduction of the genes for
      trehalose biosynthesis allowed human cells in culture to be reversibly desiccated
      for up to 5 days. Here, we have further investigated the factors that allow human
      cells to survive in the desiccated state. The most important finding is that
      vacuum greatly enhances the ability of human cells in culture to withstand
      desiccation. In fact, cells dried slowly and stored under vacuum are able to
      withstand desiccation even in the absence of added carbohydrates or polyols. In
      addition to vacuum, the rate of desiccation, the temperature at which cells are
      maintained, the degree of confluence when dried, and the presence or absence of
      light have a large effect on the ability to retain viability in the desiccated
      state. Our data are consistent with a model in which cells can retain viability
      if they are desiccated in such a way that cellular structures are maintained.
      However, gradual loss of viability may be due to damage that occurs over time in
      the desiccated state, perhaps due to free radicals. Further optimization of the
      process for desiccating and maintaining cells is required before long-term
      storage of desiccated cells can be achieved.

PMID- 11578121
TI  - Respiratory activity of isolated rat hepatocytes following cold storage and
      subsequent rewarming: a comparison of sucrose-based and University of Wisconsin
      solutions.
AB  - Investigations were carried out on the respiratory function of isolated rat
      hepatocytes after cold storage alone for periods up to 48 h in either sucrose
      based solution (SBS) or University of Wisconsin (UW) solution and after
      subsequent normothermic preincubation. In both SBS and UW, cold storage for 24 h
      depressed respiratory function (to 21 +/- 3 and 23 +/- 3 nmol O(2)/min/10(6)
      cells, respectively) compared to control cell values (31 +/- 3 and 33 +/- 5 nmol
      O(2)/min/10(6) cells; P < 0.01 in each case). However, normothermic preincubation
      for 60 min returned respiratory activity to control values (for SBS and UW
      storage: 41 +/- 6 and 40 +/- 5 nmol O(2)/min/10(6) cells; for control cells: 43
      +/- 5 and 46 +/- 6 nmol O(2)/min/10(6) cells). Storage for 48 h in both SBS and
      UW allowed further depression of respiratory activity, with no recovery after
      preincubation. Stimulation of respiration by succinate in hepatocytes stored for
      longer periods was suggestive of increased membrane permeability. Both SBS and UW
      are effective storage solutions for isolated hepatocytes for up to 24 h as judged
      by aerobic metabolism, but significant damage was expressed in both solutions
      when preservation was extended.

PMID- 11578122
TI  - Effect of intravenous platelet-activating factor on bovine pulmonary mast cells.
AB  - The effect of platelet-activating factor (PAF) on bovine pulmonary mast cells
      (MCs) was investigated in calves aged 1-4 months. PAF was administered over a 5
      min period at a rate of 50 ng/kg/min to six animals, which were killed
      approximately 10 min later. No macroscopical lesions were observed in the lung
      tissue of five control calves. On semi-thin toluidine-blue stained sections, MC
      cytoplasm showed profuse deep-blue granulation. In the lung tissues of PAF
      treated calves, striking interstitial, alveolar and interlobular oedema and
      emphysema were observed. MC granules occurred at the periphery of the cytoplasm
      and MC nuclei were easily detectable. Moreover, the number of granules in the MC
      cytoplasm was remarkably low. A few granules with some metachromatic material
      were sometimes detected outside the cell limits. Ultrastructurally, the matrix
      pattern of the MC granules in lung tissues of control calves was either amorphous
      or granular. In lung tissues of the PAF-treated calves, the granular matrix
      pattern was pronounced, varying from fine- to coarse-grained, and the MCs were of
      reduced size, with many filiform processes and exocytotic vesicles. These
      findings indicate that pulmonary MC degranulation was induced by PAF in healthy
      calves.

PMID- 11578123
TI  - Glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in dogs infected
      with canine distemper virus.
AB  - An experiment based on astrocyte immunoreactivity to glial fibrillary acidic
      protein (GFAP) was designed to determine whether the astrocyte response in canine
      distemper encephalitis (CDE) was associated with the age of the animal, type of
      lesion and the cerebellar region affected. Four histopathological types of CDE
      lesion were examined, namely acute (11 dogs), acute with necrosis (four dogs),
      subacute (22 dogs) and chronic (six dogs). The animals were divided into three
      age groups, namely, 0-2 years (27 dogs), 2.1-4 years (12 dogs), and 4.1-12 years
      (four dogs). Three different cerebellar regions were evaluated. Cerebellar
      sections from three healthy dogs were used for control purposes. The highest
      number of astrocytes occurred in the cerebellar white matter and in dogs with
      acute distemper encephalopathy. In animals with subacute distemper encephalitis,
      the numbers of astrocytes appeared to increase with age, but the opposite effect
      occurred in dogs with acute or chronic encephalitis; age appeared not to
      influence the astrocyte numbers in dogs suffering from acute encephalitis with
      necrosis.

PMID- 11578124
TI  - Morphological and immunohistochemical changes in splenic macrophages of pigs
      infected with classical swine fever.
AB  - Classical swine fever (CSF) was induced in 20 pigs by inoculation with a virulent
      strain of CSF virus to determine sequential changes (2, 4, 7, 10 and 14 days post
      inoculation) in the number and morphology of splenic macrophages (red pulp and
      lymphoid marginal zone) and thus to assess the role of these cells in the
      pathogenesis of the disease. The first splenic cells to be infected with CSF
      virus were macrophages in the marginal zone followed by other macrophage
      populations. The initial phase of CSF was associated with an increase in splenic
      macrophage numbers in the marginal zone and a decrease in the red pulp.
      Subsequently, the numbers in the red pulp increased. The study suggested that
      infection, mobilization and apoptosis of splenic macrophages play an important
      role in the spread of CSF virus in vivo. Moreover, the secretory changes that
      occurred in macrophages in the initial phase of the infection suggested that
      macrophages release chemical mediators capable of modulating pathogenesis.

PMID- 11578125
TI  - Relationship between sialoadenitis and periductal laminin expression in the
      submandibular salivary gland of NZBxNZWF(1) mice.
AB  - This study was designed to investigate the relationship between cellular
      infiltration and periductal laminin expression of the submandibular salivary
      gland in female autoimmune NZBxNZWF(1) mice, which are used as an animal model
      for secondary human Sjogren's syndrome. In NZBxNZWF(1) mice, but not in non
      autoimmune control (BALB/c) mice, early submandibular salivary gland lesions were
      characterized by infiltration of mononuclear cells around vessels and ducts in
      the interstitial tissues, increasing with age. Destruction and hyperplasia of
      ductal epithelial cells occurred, with extensive local infiltration of
      mononuclear cells. Laminin expression around the ducts was significantly higher
      in young NZBxNZWF(1) mice than that in control (BALB/c and DBA/1) mice.
      Periductal laminin expression increased in NZBxNZWF(1)mice with age. In addition
      VLA-6, which is a ligand for laminin, was expressed by the infiltrating cells.
      These results suggest that laminin expression is associated with the cellular
      infiltration of the submandibular salivary gland of NZBxNZWF(1) mice.

PMID- 11578126
TI  - Angiogenesis in squamous cell carcinomas of canine skin: an immunohistochemical
      and quantitative analysis.
AB  - In a number of recent papers, the intratumoral microvessel density (iMVD) has
      been described as a promising new prognostic factor. In this study, the
      angiogenic rate was evaluated immunohistochemically for platelet endothelial cell
      adhesion molecule (CD31) in 15 squamous cell carcinomas (SCCs) of canine skin.
      Computer image analysis was used to measure the iMVD, which increased
      progressively from differentiation grade I to IV. The iMVD was consistently and
      significantly greater in the poorly differentiated SCC cases. The correlation of
      angiogenesis data with differentiation grade of canine SCCs suggests that the
      iMVD value may provide an additional criterion for evaluating the intrinsic
      malignancy and growth potential of such tumours.

PMID- 11578127
TI  - Stimulation of the renin-angiotensin system in cats with hypertrophic
      cardiomyopathy.
AB  - Feline hypertrophic cardiomyopathy (HCM) is a disease of the ventricular
      myocardium, which may cause sudden death in cats, but neither the aetiology nor
      the effect on the circulation are well understood. Fourteen cats of either sex
      with naturally occurring HCM were studied post mortem. Their ages ranged from 9
      months to 10 years with an average age of 4.9 years. Heart weights and heart
      weight expressed as a percentage of body weight were elevated (27.9 g and 0.65%,
      respectively) as compared with normal values obtained in previous studies.
      Myocardial disarray was evident in nine of the 14 cats and moderate to severe
      fibrosis was present in six animals. To evaluate the renal renin-angiotensin
      system, semiquantitative morphometric data were obtained by means of renin
      immunohistochemistry and compared with results from an earlier study of 10
      healthy cats by the author. The juxtaglomerular index was 36.8% in the cats with
      HCM as compared with 30.6% in healthy cats. The renin-positive portion of the
      afferent arteriole was increased in cats affected by HCM to 86.0 microm as
      compared with 49.9 microm in normal cats. The increase in kidney renin values in
      cats with HCM may have been due to decreased blood pressure and reduced renal
      perfusion resulting from impaired cardiac output.

PMID- 11578128
TI  - Metallothionein expression in canine and feline mammary and melanotic tumours.
AB  - Moderate to strong immunohistochemical metallothionein (MT) positivity (MT
      expression) is associated with a poor prognosis in some human tumours. The aim of
      this study was to determine MT expression in mammary tumours and cutaneous
      melanomas in dogs and cats. Canine (67) and feline (47) mammary tumours, and
      cutaneous melanomas (canine 40, feline 26) were immunolabelled with MT monoclonal
      antibody E9. The overall incidence of MT expression of these tumours was similar
      to that observed in various human neoplasms. However, a striking interspecies
      difference was detected. In dogs, MT expression occurred in 100% of benign and
      57% of malignant mammary tumours. In cats, however, 30% of malignant mammary
      tumours expressed MT but benign mammary tumours and cases of fibroadenomatous
      hyperplasia did not. Moderate to strong MT immunoreactivity was detected in 30%
      of benign and 25% of malignant cutaneous melanomas in dogs, and in 6% of
      malignant melanomas in cats. The findings in feline mammary tumours resembled
      findings reported in human breast cancer, but the cause of tumour-associated MT
      expression is unknown. Studies are in progress to determine whether the MT state
      (apo [metal-free] or holo [metal-bound]) accounts for the paradoxical association
      of MT expression with individual types of tumours and the animal species in which
      they arise.

PMID- 11578129
TI  - T cell-dependent inducible nitric oxide synthase production and ultrastructural
      morphology in BALB/c mice infected with Mycobacterium avium subspecies
      paratuberculosis.
AB  - Euthymic BALB/c and athymic nude BALB/c mice aged 3-8 days were infected
      intraperitoneally with Mycobacterium avium subspecies paratuberculosis (ATCC
      strain 19698). After euthanasia at 5 months post-inoculation, hepatic granulomas
      were evaluated by morphometric analysis of digital images captured from light
      microscopy sections, by electron microscopy and by immunohistochemical methods.
      Euthymic mice differed from athymic mice in that (1) their hepatic granulomas
      were smaller, contained fewer bacteria, and produced more inducible nitric oxide
      synthase, and (2) their hepatic macrophages contained fewer bacteria, a higher
      percentage of degraded bacteria, and increased numbers of primary lysosomes. The
      study showed that macrophage activation was markedly less in the T cell-deficient
      athymic mice than in the euthymic mice.

PMID- 11578130
TI  - Association of jaagsiekte sheep retrovirus with pulmonary carcinoma in Sardinian
      moufflon (Ovis musimon).
AB  - Bronchiolo-alveolar carcinoma has been described in man and in several animal
      species, including cattle, dogs, opossums, goats and sheep. In sheep, a
      bronchiolo-alveolar carcinoma, known as ovine pulmonary carcinoma (OPC), is
      caused by jaagsiekte sheep retrovirus (JSRV), an exogenous type D retrovirus. In
      the mid-1980s, a severe outbreak of a disease resembling OPC was described in
      captive Sardinian moufflon (Ovis musimon). In the present study, the use of
      polymerase chain reaction (PCR) amplification of nucleic acids extracted from
      archival material established that JSRV was associated with OPC in affected
      moufflon. JSRV was detected in the lungs and mediastinal lymph nodes.
      Immunohistochemical and in-situ PCR demonstrated that in the lungs, JSRV proviral
      DNA was localized in transformed and untransformed type II pneumocytes and in the
      alveolar macrophages. In the mediastinal lymph nodes, JSRV DNA was mainly located
      in the cortical follicles and paracortex. These data suggest that JSRV is the
      cause of OPC in Sardinian moufflon, as it is in Sardinian sheep.

PMID- 11578131
TI  - Expression of cyclin kinase inhibitor p27(Kip1) in skin tumours of dogs.
AB  - Skin tumours (n=148) of epidermal or hair follicle origin were examined
      immunohistochemically to determine the expression of p27(Kip1)(p27), a cyclin
      dependent kinase inhibitor (CDKI), and of Ki-67. In normal skin, a large number
      of basal cells of the epidermis and hair follicles were positive for Ki-67 and
      many suprabasal epithelial cells were positive for p27. Most of the hair matrix
      cells were positive for Ki-67 but negative for p27. Hair papillae were strongly
      positive for p27. Squamous cell carcinomas had a p27 positive index (PI)
      significantly lower than that of trichoepitheliomas (P<0.005), basal cell tumours
      (P<0.05) and intracutaneous cornifying epitheliomas (P<0.001). In contrast, Ki-67
      PIs of squamous cell carcinomas and pilomatrixomas were significantly higher than
      those of trichoepitheliomas, basal cell tumours and intracutaneous cornifying
      epitheliomas (P<0.01 to P<0.001). No significant difference was observed between
      the Ki-67 PI values of squamous cell carcinomas and pilomatrixomas. The results
      suggested that p27 is capable of suppressing cell proliferation in the
      differentiation of normal canine skin. In spite of being a benign neoplasm,
      pilomatrixomas had a low p27 expression; this may be a reflection of the
      proliferative potential of the hair matrix. The expression of p27 may be a useful
      marker for the analysis of cell kinetics.

PMID- 11578132
TI  - Hereditary dilated cardiomyopathy in Holstein-Friesian cattle in Japan:
      association with hereditary myopathy of the diaphragmatic muscles.
AB  - This report deals with the pathology and genetic basis of dilated cardiomyopathy
      in 10 Holstein-Friesian cows aged 3-6 years, a disease similar to that reported
      in Simmental-Red Holstein and Holstein-Friesian cattle in several other
      countries. The main clinical signs were associated with systemic circulatory
      failure, and at necropsy the animals showed cardiomegaly, severe congestion and
      fibrosis of the liver, and systemic cardiac oedema. Histologically, hypertrophy
      and vacuolation of the cardiac muscle fibres and severe fibrosis were noted.
      Electron microscopically, the sarcoplasm of the hypertrophic fibres was seen to
      be filled with fine structures of low electron-density, together with thin
      filamentous material, suggesting myofibrillar lysis. The mitochondria showed
      increased size, an abnormal cristae pattern and vacuolation due to partial loss
      of cristae. Pedigree analysis of the affected cattle indicated an autosomal
      recessive mode of inheritance. The family line of this cardiomyopathy overlapped
      with that of hereditary myopathy of the diaphragmatic muscles in Holstein
      Friesian cattle, the pathological aspects and inheritance mode of which were
      reported previously. The available evidence suggested a genetic association
      between these two pathologically distinct diseases.

PMID- 11578133
TI  - Canine balloon and signet-ring cell melanomas: a histological and
      immunohistochemical characterization.
AB  - Seven tumours that were composed of balloon (n=4) or signet-ring (n=3) cells were
      investigated for a putative melanocytic origin. The tumours were located in the
      skin or the mouth cavity. In one case a sample from inguinal lymph node
      metastasis was available. Two antibodies used in man for the immunohistochemical
      diagnosis of melanomas, namely anti-Melan-A and anti-tyrosinase, were examined
      for their cross-reactivity with the corresponding canine antigens. The Melan-A
      antibody labelled all balloon cell tumours and one signet-ring cell tumour,
      whereas the anti-tyrosinase antibody was not reactive in any of the tumours. The
      Melan-A antibody also labelled a variety of canine epithelioid and spindle cell
      melanomas; non-melanocytic tumours were all negative. This study confirmed the
      occurrence of balloon and signet-ring cell melanomas in dogs. Melan-A antibody
      was found to be useful in the diagnosis of pigmented and non-pigmented canine
      melanomas.

PMID- 11578134
TI  - Experimental study of induced inflammation in the Brazilian Boa (Boa constrictor
      constrictor).
AB  - The objective of this work was to identify the cellular types present in
      inflammatory processes in the Brazilian snake, Boa constrictor constrictor. Blood
      smears were first made from three normal snakes and stained by several methods to
      identify the cell types present, thus facilitating the identification of cells in
      inflammatory processes induced in 16 further snakes by the subcutaneous
      implantation of cotton suture threads and circular coverslips. Implanted threads
      induced migration of heterophils and monocytes after 4 h, more intense monocyte
      migration after 24 h, an intense granulocytic migration inside and around the
      thread after 48 h, heterophilic granulocytes, macrophages and giant cells after 7
      days, and giant cells with a typical granuloma response and persistence of
      heterophilic cells after 15, 69 and 117 days. The cell population attached to the
      implanted coverslips after 4 h was composed of heterophils, thrombocytes,
      erythrocytes and macrophages; after 24 and 48 h heterophils predominated, and
      after 7 days heterophils, macrophages and giant cells predominated.

PMID- 11578135
TI  - A comparison of lymphatic tissues from cats with spontaneous feline infectious
      peritonitis (FIP), cats with FIP virus infection but no FIP, and cats with no
      infection.
AB  - Lymphatic tissues (spleen, mesenteric lymph nodes, thymus) from 24 cats with
      spontaneous feline infectious peritonitis (FIP) were examined by light microscopy
      and immunohistochemistry for cellularity, cellular composition, and degree of
      cellular turnover. Additionally, the formation of granulomatous lesions in
      lymphatic tissues in cats with FIP was examined. For comparison, tissues from 14
      specific pathogen-free (SPF) cats and seven cats infected with FIP virus (FIPV;
      as the result of long-term exposure) but free from FIP were examined. In cats
      with FIP, the precardial mediastinum (including site of the thymus) and
      mesenteric lymph node parenchyma were often affected by granulomatous-necrotizing
      processes. In general, lymphoid tissues showed T- and B-cell depletion, often
      including massive to complete thymic involution or atrophy. In some cases, the
      number of apoptotic lymphocytes was increased in lymphoid follicles as well as in
      T-cell zones. The number of macrophages was increased in the splenic red pulp. In
      contrast, the FIPV-exposed cats without FIP generally showed a distinct lymphoid
      hyperplasia. The findings indicated that the major difference in lymphatic
      tissues between FIPV-infected cats with FIP and those without FIP was the
      development of lymphocyte depletion in the first group and lymphocyte
      proliferation in the second.

PMID- 11578136
TI  - Osteopenia and reduced serum alkaline phosphatase activity in grazing lambs
      naturally infected with gastrointestinal nematodes.
AB  - The effect of gastrointestinal nematode infections on bone development was
      investigated in growing sheep on pasture. Forty-five weaned lambs from six groups
      in a two-factorial design incorporating stocking rate (SR; low, medium and high)
      and presence or absence of infection on pasture were sampled in the late grazing
      season. Worm counts were performed at slaughter, and the left metacarpal bones
      were excised for bone assessment. Faecal egg counts and worm burdens, primarily
      of Ostertagia circumcincta and Trichostrongylus vitrinus, were considerably
      higher in the high SR infected group ("I-High") than in comparable animals at low
      or medium SRs, whereas uninfected groups showed negligible egg excretion.
      Clinical biochemistry revealed significantly reduced serum concentrations of
      albumin, calcium and alkaline phosphatase in infected lambs. Nematode infections
      were associated with significant reductions in bone mineral density (30% at high
      SR), measured by dual energy X-ray absorptiometry, and in bone size (9%).
      Histomorphometry indicated thinning of the trabecular structure and reduced bone
      formation in the infected groups, particularly the I-High group. Bone mineral
      density, bone tissue volume and structural changes were strongly associated with
      log-transformed worm counts. The study showed that lambs suffering from moderate
      to heavy degrees of naturally acquired gastrointestinal nematode infection
      developed marked osteopenia after weaning, i.eduring the later part of the
      grazing season.

PMID- 11578137
TI  - Disseminated metastatic intramedullary melanoma in an aged grey horse.
AB  - A 12-year-old grey Warmblood stallion presented with fever of unknown origin, and
      anaemia. Five days later it had developed ataxia and become recumbent, and was
      humanely killed. At necropsy, malignant melanomas were identified in the perineal
      subcutis, spleen, and thoracic vertebral canal (T10-11). Populations of malignant
      melanoma cells were scattered throughout medullary cavities of the axial and
      appendicular skeleton, and were identified grossly as irregular areas of black to
      grey discoloration. To the authors' knowledge, this is the first report of
      disseminated intramedullary melanoma in a domestic species.

PMID- 11578138
TI  - Bronchial lesions of the late asthmatic response in BALB/c and C57BL/6 mice.
AB  - In this study, histopathological bronchial-bronchiolar lesions of the late
      asthmatic responses induced by ovalbumin in BALB/c and C57BL/6 mice were
      compared. Prominent goblet cell hyperplasia and metaplasia with mucous secretion,
      and desquamation of epithelial cells with severe infiltration of eosinophils and
      lymphocytes, were observed in the BALB/c mice; in the C57BL/6 mice, however,
      these changes were less severe. The reduced histopathological changes in the
      C57BL/6 mice were associated with a decreased infiltrate of eosinophils,
      decreased serum immunoglobulin-E (IgE) concentrations and increased serum
      interferon-gamma concentrations. The results suggest that the reduced bronchial
      lesions in C57BL/6 mice were due, at least in part, to suppression of the T
      helper (Th)2 immune response that underlies the decreased infiltration of
      lymphocytes and eosinophils into the bronchial mucosa.

PMID- 11578139
TI  - Idiopathic systemic granulomatous disease and macrophage expression of PTHrP in a
      miniature pony.
AB  - Idiopathic systemic granulomatous disease, which has been reported in horses,
      cattle and human beings, is characterized by perivascular granulomatous and
      lymphoplasmacytic inflammation in many organ systems. Diagnosis is based on the
      exclusion of possible viral, fungal or bacterial causes. The disease was
      identified in a miniature pony with widespread lymphoplasmacytic and
      granulomatous inflammation, special staining techniques having revealed no
      evidence of any aetiological agent. Skin lesions, which were severe, consisted of
      hyperkeratosis and serocellular crust formation, with inflammatory infiltrates in
      a perivascular to diffuse pattern in both the superficial and deep dermis.
      Inflammatory infiltrates were also present in lymph nodes and around the blood
      vessels in most organs. Immunohistochemically, both CD3-positive T lymphocytes
      and BLA36-positive B lymphocytes were identified in the inflammatory infiltrates,
      and macrophages were immunolabelled for parathyroid hormone-related protein, a
      factor associated with hypercalcaemia in human beings with granulomatous
      diseases.

PMID- 11578140
TI  - Disseminated histoplasmosis in a sea otter (Enhydra lutris).
AB  - Disseminated histoplasmosis was diagnosed in a 4.75-year-old, captive female sea
      otter (Enhydra lutris). At necropsy, the liver was found to be markedly swollen,
      with many nodules (4-12 mm in diameter). Histologically, macrophages containing
      numerous intracellular yeast-like organisms were noted in the liver, spleen, lung
      and kidney. These organisms were labelled immunohistochemically with anti
      histoplasma yeast antibody. Ultrastructurally, the yeast-like organisms, 2-4
      microm in diameter, were found within membranous structures in the cytoplasm of
      macrophages. This is the first confirmed report of disseminated histoplasmosis in
      sea otters.

PMID- 11578141
TI  - Abomasal ulcers in captive white-tailed deer (Odocoileus virginianus).
AB  - Abomasal ulceration was noted in 32 of 200 white-tailed deer. Ulceration was most
      common in the abomasal pylorus and at the abomasal-duodenal junction. Abomasal
      ulceration was characterized by focal to multifocal, sharply demarcated areas of
      coagulation necrosis and haemorrhage extending through the mucosa, with fibrin
      thrombi in mucosal blood vessels of small diameter. Ulcerated areas were often
      covered by a mixture of mucus, debris and neutrophils. Visible bacteria were not
      associated with ulcerative lesions. All deer with abomasal ulceration had
      intercurrent disease, including bacterial pneumonia, enterocolitis,
      intussusception, chronic diarrhoea, capture myopathy, or experimentally induced
      tuberculosis. The anatomical distribution of abomasal ulcers in this population
      of captive white-tailed deer resembled that seen in veal calves.

PMID- 11578142
TI  - Acute disseminated toxoplasmosis in a captive three-toed sloth (Bradypus
      tridactylus).
AB  - Fatal toxoplasmosis was diagnosed in a captive three-toed sloth (Bradypus
      tridactylus), an arboreal species of the tropical rainforests of South and
      Central America. In view of its specialized lifestyle and ecosystem and its low
      metabolic rate, B. tridactylus would seem to warrant further investigation in
      respect of its susceptibility to Toxoplasma gondii.

PMID- 11578143
TI  - Genetic background but not metallothionein phenotype dictates sensitivity to
      cadmium-induced testicular injury in mice.
AB  - Sensitivity to cadmium (Cd)-induced testicular injury varies greatly among mouse
      strains. For instance, 129/SvJ (129) mice are highly sensitive while C57BL/6J
      (C57) mice are refractory to Cd-induced testicular injury. Metallothionein (MT),
      a Cd-binding protein, is thought to be responsible for the strain susceptibility
      to Cd toxicity. In this study, MT-I/II knockout (MT-null) and wild-type 129 mice
      were used to determine the role of MT in Cd-induced testicular injury. Two
      additional strains of mice (C57 and the C57 x 129 F1cross) were also used to help
      define the role of genetic background in Cd toxicity. Mice were given 5-20
      micromol/kg ip CdCl(2) and testicular injury was examined 24 h later by
      histopathology and testicular hemoglobin concentration. Cd produced dose
      dependent testicular injury in all strains of mice, except for C57 mice, in which
      testicular injury could not be produced. MT-null mice were more sensitive than
      C57 x 129 mice but were equally sensitive as 129 mice to Cd-induced testicular
      injury. Fourteen days after 15 micromol/kg ip Cd administration, testicular
      atrophy was evident in MT-null, 129, and C57 x 129 mice but was absent in C57
      mice. The resistance of C57 mice to Cd-induced testicular injury could not be
      attributed solely to a decreased uptake of (109)Cd nor to a greater amount of
      testicular MT. Microarray analysis revealed a higher expression of glutathione
      peroxidase in the testes of C57 mice, as well as genes encoding antioxidant
      components and DNA damage/repair, but their significance to Cd-induced injury is
      not immediately clear. Thus, this study demonstrates that it is genetic strain,
      not MT genotype, that is mechanistically important in determining susceptibility
      to Cd-induced testicular injury.

PMID- 11578145
TI  - Contribution of enzymic alpha, gamma-elimination reaction in detoxification
      pathway of selenomethionine in mouse liver.
AB  - The objective of this study was to clarify the detoxification pathways of
      selenomethionine (SeMet) in mouse liver. It has been postulated that SeMet may be
      metabolized to selenocysteine (SeCyH) via a pathway similar to methionine (Met).
      CySeH may be decomposed to H(2)Se, which is consequently methylated to CH(3)SeH,
      (CH(3))(2)Se, and (CH(3))(3)Se(+). In this study, we estimated that the median
      lethal single oral dose (LD(50)) was 67.0 mg/kg. We also found that
      (CH(3))(3)Se(+) was quickly produced in mouse liver after single oral
      administration of SeMet. This result suggested the existence of a quick
      alpha,gamma-elimination pathway. We measured the amounts of alpha-ketobutyrate,
      NH(3), and CH(3)SeH produced by enzymic alpha,gamma-elimination reaction of SeMet
      in the liver of periodate-oxidized adenosine (PAD) or D,L-propargylglycine (PPG)
      treated mice in order to verify the existence of alpha,gamma-elimination enzyme.
      PAD is an inhibitor of S-adenosylhomocysteinase (EC 3.3.1.1), which is necessary
      for conversion of SeMet to SeCyH. PPG is an effective inhibitor of the pyridoxal
      5'-phosphate (PLP)-containing enzyme bacterial L-methionine gamma-lyase (EC
      4.4.1.11) contributing to the alpha,gamma-elimination reaction of SeMet and
      cystathionine gamma-lyase (EC 4.4.1.1) relating to conversion of SeMet to SeCyH.
      When SeMet was incubated with the S9 fraction from liver of PAD-treated mice, the
      formation of alpha-ketobutyrate was much the same as that from nontreated mouse
      liver. However, the amount of alpha-ketobutyrate formed significantly decreased
      in the reaction of SeMet with S9 fraction from the liver of PPG-treated mice. In
      an in vivo experiment using mice treated with PAD before a toxic dosage of SeMet,
      the amount of SeMet in the liver decreased and the amount of acid-volatile Se
      derived from CH(3)SeH increased gradually. This phenomenon was not observed in
      the PPG-pretreated group. Furthermore, the protein fraction that had the
      alpha,gamma-elimination enzyme activity was found in mouse liver cytosol by gel
      chromatographic technique. The results of this study indicated that SeMet was
      directly metabolized to CH(3)SeH by an alpha,gamma-elimination enzyme analogous
      to bacterial L-methionine gamma-lyase, in addition to the generally acceptable
      pathway via SeCyH.

PMID- 11578144
TI  - Aluminium lactate treatment of DQ12 quartz inhibits its ability to cause
      inflammation, chemokine expression, and nuclear factor-kappaB activation.
AB  - In 1997, an IARC Working Group classified quartz (crystalline silica) as a Group
      1 lung carcinogen, but only in some industries, i.e., the quartz hazard is a
      variable entity. The reactivity of the quartz surface may underlie its ability to
      cause inflammation, and treatments that ameliorate this reactivity will reduce
      the quartz hazard. In this study we treated quartz (Q) with aluminium lactate
      (AL), a procedure that is reported to decrease the quartz hazard, and explored
      the effect this had on the highly reactive quartz surface and on proinflammatory
      events in rat lungs. Aluminium lactate-treated quartz showed a reduced surface
      reactivity as measured by electron spin resonance and the hemolysis assay.
      Eighteen hours after instillation of Q into the rat lung, there was massive
      inflammation as indicated by the number of neutrophils in the bronchoalveolar
      lavage (BAL). In addition, Q induced an increase in BAL macrophage inflammatory
      protein-2 (MIP-2) while ALQ had no significant effect compared to control.
      Epithelial damage, as indicated by BAL protein and gamma glutamyl transpeptidase,
      also increased with Q but not with ALQ. Furthermore, Q induced an increase in MIP
      2 mRNA by BAL cells while ALQ had no effect compared to controls. There was an
      increase in nuclear binding of the transcription nuclear factor kappaB (NF
      kappaB) in the Q-exposed BAL cells and again no effect on nuclear NF-kappaB
      binding in BAL cells from ALQ-exposed rats. In conclusion, treatment of the
      quartz surface with aluminium lactate reduced the reactivity of the particles
      both in terms of hydroxyl radical generation and in terms of the induction of
      molecular signaling events leading to inflammation.

PMID- 11578146
TI  - Protective effects of amifostine and its analogues on sulfur mustard toxicity in
      vitro and in vivo.
AB  - Sulfur mustard (bis(2-chloroethyl)sulfide, SM) is a highly reactive bifunctional
      alkylating agent that forms sulfonium ions in the body. SM alkylates DNA, leading
      to DNA strand breaks and cell death in a variety of cell types and tissues.
      Although several approaches have been proposed to challenge the toxic action(s)
      of SM, no satisfactory treatment regimen has evolved. The synthetic aminothiol
      amifostine, earlier known as WR-2721 (S-2-(3-aminopropylamino)ethyl
      phosphorothioate), has been extensively used as a chemical radioprotector for the
      normal tissues in cancer radiotherapy and chemotherapy. SM is known as a
      radiomimetic agent and this prompted us to evaluate the protective efficacy of
      amifostine (2.5 mM) and three of its analogues, DRDE-06 (S-2 (3-aminopropylamino)
      ethyl phenyl sulfide), DRDE-07 (S-2 (2-aminoethylamino) ethyl phenyl sulfide),
      and DRDE-08 (S-2 (4-aminobutylamino) ethyl phenyl sulfide), against SM toxicity
      in rat liver slices. Of the four agents tested, a 30-min pretreatment of
      amifostine and DRDE-07 enhanced the LC50 (a concentration producing 50% leakage
      of lactate dehydrogenase (LDH) or alanine aminotransferase (ALT)) of SM by 5.9-
      and 3.3-fold for LDH and 10.2- and 5.5-fold for ALT, respectively. Except DNA
      fragmentation, both these agents significantly attenuated the loss of
      intracellular K(+) and mitochondrial integrity (MTT assay), depletion of GSH
      levels, and histopathology produced by a toxic concentration (80 microM) of SM.
      However, when amifostine and DRDE-07 were introduced 2 h after SM, no significant
      protection was observed. SM (77.5 or 155 mg/kg) was also applied dermally on
      female albino mice and challenged by 0.20 LD50 (po) of amifostine, DRDE-06, DRDE
      07, or DRDE-08 at -30 min, 0 min, or +6 h. Protection was observed only when the
      agents were administered at -30 min or 0 min; posttreatment (+6 h) did not offer
      any protection. The magnitude of in vivo protection was in the following order:
      DRDE-07 >or= amifostine > DRDE-08 > DRDE-06. Gas chromatographic analysis showed
      that there was no direct chemical interaction between SM and the antidotes. The
      po LD50s of amifostine, DRDE-06, DRDE-07, and DRDE-08 were 1049, 1345, 1248, and
      951 mg/kg, respectively. Both in vitro and in vivo data indicate promising roles
      of amifostine and DRDE-07 as prophylactic agents against SM poisoning.

PMID- 11578147
TI  - Microarray analysis of differential gene expression in lead-exposed astrocytes.
AB  - The toxic metal lead is a widespread environmental health hazard that can
      adversely affect human health. In an effort to better understand the cellular and
      molecular consequences of lead exposure, we have employed cDNA microarrays to
      analyze the effects of acute lead exposure on large-scale gene expression
      patterns in immortalized rat astrocytes. Our studies identified many genes
      previously reported to be differentially regulated by lead exposure.
      Additionally, we have identified novel putative targets of lead-mediated
      toxicity, including members of the family of calcium/phospholipid binding
      annexins, the angiogenesis-inducing thrombospondins, collagens, and tRNA
      synthetases. We demonstrate the ability to distinguish lead-exposed samples from
      control or sodium samples solely on the basis of large-scale gene expression
      patterns using two complementary clustering methods. We have confirmed the
      altered expression of candidate genes and their encoded proteins by RT-PCR and
      Western blotting, respectively. Finally, we show that the calcium-dependent
      phospholipid binding protein annexin A5, initially identified as a differentially
      regulated gene by our microarray analysis, is directly bound and activated by
      nanomolar concentrations of lead. We conclude that microarray technology is an
      effective tool for the identification of lead-induced patterns of gene expression
      and molecular targets of lead.

PMID- 11578148
TI  - The mycotoxin ochratoxin A alters intestinal barrier and absorption functions but
      has no effect on chloride secretion.
AB  - Ochratoxin A (OTA) is a mycotoxin that contaminates cereals and animal feed and
      causes nephropathy to a variety of animal species. OTA is also known as a potent
      immunotoxic, teratogenic, and carcinogenic mycotoxin. In addition, OTA ingestion
      induces intestinal injuries, including inflammation and diarrhea. With the aim to
      study the cellular mechanisms associated with the intestinal toxicity of OTA, two
      human epithelial intestinal cell lines (HT-29-D4 and Caco-2-14 cells), widely
      used as in vitro models for the intestinal epithelium, were incubated with OTA.
      The main effects of the mycotoxin were an inhibition of cellular growth and a
      dramatic decrease of transepithelial resistance in both cell lines. Since
      transepithelial resistance reflects the organization of tight junctions over the
      cell monolayer, these data may suggest that OTA could potentiate its own
      absorption through paracellular pathways. OTA induced a 60% decrease of sodium
      dependent glucose absorption but increased the absorption of fructose and L
      serine in HT-29-D4 cells. Moreover, the mycotoxin did not inhibit the cAMP
      dependent chloride secretion through the cystic fibrosis transmembrane
      conductance regulator channel. The inhibitory effect of OTA on active glucose
      transport was partially antagonized by L-phenylalanine, but not by alpha
      tocopherol, suggesting that the toxicity of OTA could result from an inhibition
      of protein synthesis, rather than an induction of lipid peroxidation. In
      particular, OTA affected the protein content of plasma membrane microdomains,
      which are known to regulate tight junction assembly and intestinal transport
      activity. Taken together, these data showed that OTA alters both barrier and
      absorption functions of the intestinal epithelium.

PMID- 11578149
TI  - Arsenite is a cocarcinogen with solar ultraviolet radiation for mouse skin: an
      animal model for arsenic carcinogenesis.
AB  - Although epidemiological evidence shows an association between arsenic in
      drinking water and increased risk of skin, lung, and bladder cancers, arsenic
      compounds are not animal carcinogens. The lack of animal models has hindered
      mechanistic studies of arsenic carcinogenesis. Previously, this laboratory found
      that low concentrations of arsenite (the likely environmental carcinogen) which
      are not mutagenic can enhance the mutagenicity of other agents, including
      ultraviolet radiation (UVR). This enhancing effect appears to result from
      inhibition of DNA repair by arsenite. Recently we found that low concentrations
      of arsenite disrupted p53 function and upregulated cyclin D1. These results
      suggest that the failure to find an animal model for arsenic carcinogenesis is
      because arsenite is not a carcinogen per se, but rather acts as an enhancing
      agent (cocarcinogen) with a genotoxic partner. We tested this hypothesis with
      solar UVR as carcinogenic stimulus in hairless Skh1 mice. Mice given 10 mg/l
      sodium arsenite in drinking water for 26 weeks had a 2.4-fold increase in yield
      of tumors after 1.7 KJ/m(2) UVR three times weekly compared with mice given UVR
      alone. No tumors appeared in mice given arsenite alone. The tumors were mostly
      squamous cell carcinomas, and those occurring in mice given UVR plus arsenite
      appeared earlier and were much larger and more invasive than in mice given UVR
      alone. These results are consistent with the hypothesis that arsenic acts as a
      cocarcinogen with a second (genotoxic) agent by inhibiting DNA repair and/or
      enhancing positive growth signaling.

PMID- 11578150
TI  - Durable treatment-free remission after high-dose cyclophosphamide therapy for
      previously untreated severe aplastic anemia.
AB  - BACKGROUND: Severe aplastic anemia is a life-threatening bone marrow failure
      disorder. High-dose cyclophosphamide therapy followed by allogeneic bone marrow
      transplantation cures the disease. However, it requires a suitable donor and
      carries the risk for graft-versus-host disease. A small pilot study demonstrated
      that high-dose cyclophosphamide therapy without bone marrow transplantation leads
      to durable, treatment-free complete remission. OBJECTIVE: To confirm the safety
      and efficacy of high-dose cyclophosphamide therapy alone in patients with severe
      aplastic anemia. DESIGN: Uncontrolled clinical trial. SETTING: Three tertiary
      care hospitals. PATIENTS: 19 patients with untreated severe aplastic anemia.
      INTERVENTION: Cyclophosphamide, 50 mg/kg of body weight per day for 4 consecutive
      days. MEASUREMENTS: Probability of response and overall survival were measured.
      Complete remission was defined as normal blood count for age and sex. Partial
      remission was defined as independence from transfusion and an absolute neutrophil
      count greater than 0.5 x 10(9) cells/L without growth factor support.
      Nonresponders were patients who remained transfusion dependent or died. Relapse
      was defined as no longer meeting criteria for partial or complete remission.
      RESULTS: The median time to an absolute neutrophil count of 0.5 x 10(9) cells/L
      was 49 days. The probability of survival was 84% (95% CI, 59% to 95%) at 24
      months. The probability of achieving treatment-free remission was 73% (CI, 51% to
      91%) at 24 months, and the probability of achieving complete remission was 65%
      (CI, 39% to 89%) at 50 months. No responding patients have had relapse or have
      developed secondary clonal disorders. CONCLUSIONS: High-dose cyclophosphamide
      therapy without bone marrow transplantation produces durable treatment-free
      remission in severe aplastic anemia. This approach deserves further study in
      patients with severe aplastic anemia who are not suitable candidates for
      allogeneic bone marrow transplantation.

PMID- 11578151
TI  - Determinants of vancomycin resistance and mortality rates in enterococcal
      bacteremia. a prospective multicenter study.
AB  - BACKGROUND: Enterococcus species are major nosocomial pathogens and are
      exhibiting vancomycin resistance with increasing frequency. Previous studies have
      not resolved whether vancomycin resistance is an independent risk factor for
      death in patients with invasive disease due to Enterococcus species or whether
      antibiotic therapy alters the outcome of enterococcal bacteremia. OBJECTIVE: To
      determine whether vancomycin resistance is an independent predictor of death in
      patients with enterococcal bacteremia and whether appropriate antimicrobial
      therapy influences outcome. DESIGN: Prospective observational study. SETTING:
      Four academic medical centers and a community hospital. PATIENTS: All patients
      with enterococcal bacteremia. MEASUREMENTS: Demographic characteristics;
      underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II
      scores; antibiotic therapy, immunosuppression, and procedures before onset; and
      antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day
      survival. RESULTS: Of 398 episodes, 60% were caused by E. faecalis and 37% were
      caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or
      intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium
      isolates showed reduced susceptibility to quinupristin-dalfopristin. Previous
      vancomycin use (odds ratio [OR], 5.82 [95% CI, 3.20 to 10.58]; P < 0.001),
      previous corticosteroid use (OR, 2.43 [CI, 1.22 to 4.86]; P = 0.01), and total
      APACHE II score (OR, 1.06 per unit change [CI, 1.02 to 1.10 per unit change]; P =
      0.003) were associated with vancomycin-resistant enterococcal bacteremia. The
      mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [CI, 1.56 to
      9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [CI, 1.14 to 3.88]; P = 0.02),
      and APACHE II score (OR, 1.10 per unit change [CI, 1.05 to 1.14 per unit change];
      P < 0.001) were associated with 14-day mortality. Among patients with
      monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy
      within 48 hours independently predicted survival (OR for death, 0.21 [CI, 0.06 to
      0.80]; P = 0.02). CONCLUSIONS: Vancomycin resistance is an independent predictor
      of death from enterococcal bacteremia. Early, effective antimicrobial therapy is
      associated with a significant improvement in survival.

PMID- 11578152
TI  - Effect of estrogen plus progestin on risk for biliary tract surgery in
      postmenopausal women with coronary artery disease. The Heart and
      Estrogen/progestin Replacement Study.
AB  - BACKGROUND: Animal and observational epidemiologic studies have reported that
      estrogens may increase the risk for gallstones. No major clinical trials have
      examined the effect of estrogen plus progestin therapy in postmenopausal women on
      the risk for biliary tract surgery. OBJECTIVE: To determine the effect of
      estrogen plus progestin on the risk for biliary tract surgery in postmenopausal
      women with known coronary artery disease. DESIGN: Randomized, double-blind
      placebo-controlled trial of postmenopausal hormone therapy for coronary heart
      disease. SETTING: 20 U.S. clinical centers. PARTICIPANTS: 2253 postmenopausal
      women with a gallbladder, 44 to 79 years of age at baseline, in the Heart and
      Estrogen/progestin Replacement Study (HERS). INTERVENTION: Conjugated equine
      estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, daily in one
      tablet or identical placebo. MEASUREMENTS: Documented biliary tract surgery.
      RESULTS: A total of 147 women (7%) were hospitalized for biliary tract surgery in
      HERS. Treatment with estrogen plus progestin resulted in a marginally significant
      38% increase in the relative risk for biliary tract surgery (P = 0.05). A small
      absolute difference in risk suggested that for every 185 women treated with
      estrogen plus progestin, one additional woman had biliary tract surgery per year.
      After adjustment for baseline and in-study statin use, the association was
      attenuated further (P = 0.09). After adjustment for treatment assignment and
      other variables, increased body mass index, fibric acid use, and a history of
      nonsurgical gallbladder disease were associated with an increased risk for
      biliary tract surgery, whereas statin use was associated with a decreased risk
      (for each comparison, P < 0.05). CONCLUSION: Estrogen plus progestin therapy
      among postmenopausal women with known coronary disease resulted in a marginally
      significant increase in the risk for biliary tract surgery.

PMID- 11578153
TI  - Delayed-onset heparin-induced thrombocytopenia and thrombosis.
AB  - BACKGROUND: Heparin-induced thrombocytopenia is a prothrombotic drug reaction
      caused by platelet-activating antibodies that recognize complexes of platelet
      factor 4 and heparin. OBJECTIVE: To describe a syndrome termed delayed-onset
      heparin-induced thrombocytopenia, in which thrombocytopenia and thrombotic events
      begin 5 or more days after withdrawal of heparin. DESIGN: Case series. SETTING:
      Secondary and tertiary care hospitals. PATIENTS: 12 patients who presented with
      serologically confirmed, delayed-onset heparin-induced thrombocytopenia,
      including 6 outpatients presenting after hospital discharge. MEASUREMENTS: The
      platelet serotonin-release assay was used to measure IgG-induced heparin
      dependent and heparin-independent platelet activation; an enzyme immunoassay that
      detects IgG against platelet factor 4-heparin complexes was also used. RESULTS:
      Patients with delayed-onset heparin-induced thrombocytopenia presented with
      thrombocytopenia and associated thrombosis a mean of 9.2 days (range, 5 to 19
      days) after stopping heparin therapy. Nine patients received additional heparin,
      with further decrease in platelet counts. Compared with controls, patients with
      delayed-onset heparin-induced thrombocytopenia had higher titers of IgG
      antibodies to platelet factor 4-heparin and greater IgG-induced heparin-dependent
      and heparin-independent platelet activation. CONCLUSIONS: Delayed-onset heparin
      induced thrombocytopenia should be suspected when patients present with
      thrombocytopenia and thrombosis up to 3 weeks after exposure to heparin. This
      syndrome could be caused by high titers of platelet-activating IgG induced by
      heparin.

PMID- 11578154
TI  - Alternative medicine: a "mirror image" for scientific reasoning in conventional
      medicine.
AB  - A reflection on the scientific behavior of adherents of conventional medicine
      toward one form of alternative medicine-homeopathy-teaches us that physicians do
      reject seemingly solid evidence because it is not compatible with theory. Further
      reflection, however, shows that physicians do the same within conventional
      medical science: Sometimes they discard a theory because of new facts, but at
      other times they cling to a theory despite the facts. This essay highlights the
      seeming contradiction and discusses whether it still permits the building of
      rational medical science. We propose that rational science is compatible with
      physicians' behavior, provided that physicians acknowledge the subjective element
      in the evaluation of science, as exemplified in the crossword analogy by the
      philosopher Haack. This type of thinking fits very well with the Bayesian
      approach to decision making that has been advocated for decades in clinical
      medicine. It does not lead to complete and uncontrollable subjectivity because
      discernment between rivaling explanations is still possible through argument and
      counterargument.

PMID- 11578155
TI  - Core safeguards for clinical research with adults who are unable to consent.
AB  - The National Bioethics Advisory Commission has proposed new safeguards for
      clinical research with adults who are unable to consent. Three other major U.S.
      groups have also proposed additional safeguards for this population, and existing
      Canadian and European guidelines already include such safeguards. While these six
      guidelines agree on some safeguards, they disagree on others. To allow important
      research to proceed while protecting adults who are unable to consent, it will be
      crucial to resolve these differences. This paper uses a side-by-side comparison
      of these six guidelines to highlight their major points of consensus, analyze
      their significant differences, and distill six core safeguards.

PMID- 11578156
TI  - Aplastic anemia: which treatment?.

PMID- 11578157
TI  - Implications and challenges using practice guidelines for chronic angina.

PMID- 11578158
TI  - Guidelines for the management of patients with chronic stable angina: diagnosis
      and risk stratification.
AB  - Patients with suspected chronic stable angina can be evaluated in three stages.
      In stage one, the clinician uses information from the history, physical
      examination, laboratory tests for diabetes and hyperlipidemia, and resting
      electrocardiography to estimate the patient's probability of coronary artery
      disease (CAD). In stage two, additional testing for patients with a low
      probability of CAD focuses on diagnosing noncoronary causes of chest pain.
      Patients with a high probability of CAD have stress tests to assess their risk
      from CAD, and patients with an intermediate probability of CAD have stress tests
      to estimate the probability of CAD and assess their risk from CAD. Most patients
      with new-onset angina can start stress testing with exercise electrocardiography.
      The initial stress test should be a stress imaging procedure for patients with
      rest ST-segment depression greater than 1 mm, complete left bundle-branch block,
      ventricular paced rhythm, preexcitation syndrome, or previous revascularization
      with percutaneous coronary angioplasty or coronary artery bypass grafting.
      Patients who cannot exercise can have an imaging procedure with stress induced by
      pharmacologic agents. In stage three, patients with a predicted average annual
      cardiac mortality rate between 1% and 3% should have a stress imaging study or
      coronary angiography with left ventriculography. Those with a known left
      ventricular dysfunction should have cardiac catheterization. Patients with CAD
      who have an estimated annual mortality rate greater than 3% should have cardiac
      catheterization to determine whether their anatomy is suitable for
      revascularization. Patients with an estimated annual mortality rate less than 1%
      can begin to receive medical therapy.

PMID- 11578159
TI  - Prevention of bleeding in older patients taking warfarin.

PMID- 11578160
TI  - Prevention of bleeding in older patients taking warfarin.

PMID- 11578162
TI  - Inflation of precision in medical reports.

PMID- 11578163
TI  - Severe liver injury.

PMID- 11578166
TI  - "I wish things were different": expressing wishes in response to loss, futility,
      and unrealistic hopes.

PMID- 11578169
TI  - Novel coordination polymers with mixed ligands and orientated enantiomers.

PMID- 11578170
TI  - Characterization and bonding of the cation [Ge[N(C6H3-2,6-i-Pr2)CMe](2)CH](+):
      comparison with the isoelectronic Ga[N(C6H3-2,6-i-Pr2)CMe](2)CH.

PMID- 11578171
TI  - A new beta-diketiminate ligand carrying a functional group on the carbon
      framework. Synthesis and characterization of a linear polymeric copper(I)
      complex.

PMID- 11578172
TI  - The first 8-vertex monocarbon metallacarborane with an "isolated" boron-capped
      pentagonal bipyramidal cage. Synthesis and molecular structure of capped closo
      2,2-(Ph(3)P)(2)-2-H-3,6,8-(MeO)(3)-RuCB(6)H(4).

PMID- 11578173
TI  - [Ni(4,4-bpy)(2)(H2PO4)2]*C4H9OH*H2O: a novel metal phosphate that exhibits
      interpenetration of 2D net into 3D framework.

PMID- 11578174
TI  - Mn(2)(CO)(6)(mu-CO)(mu-S(2)): the simplest disulfide of manganese carbonyl.

PMID- 11578175
TI  - Spectroscopic studies on iron complexes of different anthracyclines in aprotic
      solvent systems.
AB  - Iron complexes of daunorubicin, idarubicin, pirarubicin, and doxorubicin in
      anhydrous DMF were studied by UV/vis, CD, fluorescence, Mossbauer, and EPR
      spectroscopy. Titration studies of the metal-free anthracyclines showed one (UV
      detectable) deprotonation step requiring 2 equiv of base, compared to 1 equiv for
      quinizarine. Metal complexation was studied at three different metal/ligand
      ratios, and with increasing amounts of base. The results obtained from optical
      spectroscopy show the existence of two different complex species and give clear
      indications for the requirements of metal complexation. Complex species I, formed
      at a low iron-to-ligand ratio, is less dependent on base addition than complex
      species II formed with equimolar ferric ion. EPR and Mossbauer experiments
      provide further insight into the structures of both complex species. Lack of spin
      density of the Mossbauer samples in EPR indicates spin coupling between the metal
      centers. Mossbauer spectra consist of single quadrupole doublets with values
      typical for high-spin ferric ion in an octahedral arrangement. The Mossbauer
      spectroscopic features at 7 T exclude the presence of S = 0 dimers. Complex I
      represents a monomeric ferric iron complex whereas complex II is consistent with
      a more or less aggregrated oligomeric Fe-anthracycline system.

PMID- 11578176
TI  - Magnetic and electronic properties in novel terpyridine-based nitroxide
      complexes: strong radical-metal interaction via a pyridyl ring.
AB  - Transition metal complexes of 2-[4'-(2,2':6',2' '-terpyridyl)]-(4,4,5,5
      tetramethylimidazolinyl-3-oxide-1-oxyl) (terpy-NIT) and 2-[4'-(2,2':6',2' '
      terpyridyl)]-(4,4,5,5-tetramethylimidazolinyl-1-oxyl) (terpy-IM) have been
      prepared. Whereas the pyridyl fragments of the free ligands are in an anti
      conformation, the complexes are obtained by coordination of two terpyridines in a
      syn conformation, forming a distorted octahedron around the metal center:
      [M(terpy-NIT)(2)](ClO(4))(2) (M = Ni(II) 1, Zn(II) 2, Cu(II) 3) and [M(terpy
      IM)(2)](ClO(4))(2) (M = Ni(II) 4, Zn(II) 5). The ligands and their complexes have
      been characterized by FAB-MS, UV-vis, FT-IR spectroscopies, elemental analysis,
      and by EPR spectroscopy and susceptibility measurements. Single-crystal X-ray
      diffraction have been performed on the terpy-NIT ligand and on complexes 1, 4,
      and 5 giving following crystal data: terpy-NIT, monoclinic, P2(1)/c, Z = 4, a =
      14.2186(5), b = 12.9129(6), c = 11.704(1) A, beta = 108.615(4) degrees; 1,
      orthorhombic, P(n a 2(1)), Z = 4, a = 23.6367(6), b = 8.7836(1), c = 24.2748(7)
      A; 4, monoclinic, P2(1), Z = 1, a = 8.738(1), b = 25.010(1), c = 11.704(1) A,
      beta = 102.849(3) degrees; 5, monoclinic, P2(1), Z = 1, a = 8.7463(2), b =
      25.0833(5), c = 11.8168(3) A, beta = 102.757(3) degrees. For complexes 1 and 3,
      an antiferromagnetic behavior has been found and parametrized by considering a
      symmetric magnetic trimer, highlighting a strong intramolecular coupling between
      the metal and the radicals (average values 2J(M-NIT) = -19.6 K for M = Ni and 
      22.8 K for M = Cu). In the case of compound 4, an asymmetric magnetic trimer has
      been used to model the antiferromagnetic interactions (2J(Ni-IM1) = -13.0 K,
      2J(Ni-IM2) = -5.6 K). The shape of the EPR spectra of complexes 2, 3, and 5 in
      solution indicates the intermediate exchange limit, of the order of a few mK,
      between the two nitroxide radicals through the pyridyl-metal-pyridyl fragment.

PMID- 11578177
TI  - Photophysical properties of TiO(2) surfaces modified with dinuclear RuRu and RuOs
      polypyridyl complexes.
AB  - The photophysical properties of nanoporous TiO(2) surfaces modified with two new
      Ru(II)-(bpt)-Ru(II) and Ru(II)-(bpt)-Os(II) polypyridyl complexes are reported.
      These dyads have been prepared by a two-step synthetic pathway. In the first
      step, [Ru(dcbpy)(2)Cl(2)], where dcbpy is 4,4'-dicarboxy-2,2-bipyridyl, was
      reacted with the bridging ligand 3,5-bis(pyridin-2-yl)-1,2,4-triazole (Hbpt) to
      yield the mononuclear precursor Na(3)[Ru(dcbpy)(2)(bpt)].3H(2)O. Subsequent
      reaction of this compound with either [Ru(bpy)(2)Cl(2)] or [Os(bpy)(2)Cl(2)]
      yields the Ru(II)-Ru(II) and Ru(II)-Os(II) dyads. Electrochemical data, together
      with time-resolved transient absorption spectroscopy and the investigation of the
      incident-photon-to-current-efficiency (IPCE), have been used to obtain a detailed
      picture of the photoinduced charge injection properties of these dyads. These
      measurements indicate that for the heterosupramolecular triad based on Ru(II)
      (bpt)-Ru(II), the final product species obtained upon charge injection is
      TiO(2)(e)-Ru(II)Ru(III). For the mixed metal Ru(II)-(bpt)-Os(II) dyad, both metal
      centers inject efficiently into the semiconductor surface and as a result
      TiO(2)(e)-Ru(II)Os(III) is obtained as a single charge-separated product.

PMID- 11578178
TI  - Hydrothermal synthesis and structure determination from powder data of new three
      dimensional titanium(IV) diphosphonates Ti(O(3)P-(CH(2))(n)-PO(3)) or MIL-25(n)
      (n = 2, 3).
AB  - Ti(O(3)P-(CH(2))(n)-PO(3)) or MIL-25(n) (n = 2, 3) were prepared under
      hydrothermal conditions (4 days, 463 K, autogenous pressure). Their structures
      were determined ab initio from X-ray diffraction powder data. MIL-25(2) is
      triclinic (space group P-1 (no. 2)), with a = 5.033(1), b = 5.092(1), c =
      6.859(1) A, alpha = 95.860(1) degrees, beta = 99.994(1) degrees, gamma =
      118.217(1) degrees, and Z = 2. MIL-25(3) exhibits an orthorhombic symmetry (space
      group Cm2m (no. 38)), with a = 5.230(1), b = 8.451(1), c = 17.400(2) A, and Z =
      4. Their three-dimensional structures are built up from TiO(6) titanium(IV)
      octahedra linked together via diphosphonate groups. This leads to pillared
      structures whose inorganic sheets are closely related to those of the alphaTiP
      titanium phosphate structure.

PMID- 11578179
TI  - Synthesis and reactivity of bridging and terminal hydrosulfido palladium and
      platinum complexes. Crystal structures of [NBu4]2[(Pt(c6F5)2(mu-SH)]2],
      [Pt(C6F5)2(PPh3)[S(H)AgPPh3]], and [Pt(C6F5)2(PPh3)[S(AuPPh3)2]].
AB  - The reactions of the hydroxo complexes [M(2)R(4)(mu-OH)(2)](2)(-) (M = Pd, R =
      C(6)F(5), C(6)Cl(5); M = Pt, R = C(6)F(5)), [[PdR(PPh(3))(mu-OH)](2)] (R =
      C(6)F(5), C(6)Cl(5)), and [[Pt(C(6)F(5))(2)](2)(mu-OH)(mu-pz)](2-) (pz =
      pyrazolate) with H(2)S yield the corresponding hydrosulfido complexes
      [M(2)(C(6)F(5))(4)(mu-SH)(2)](2-), [[PdR(PPh(3))(mu-SH)](2)], and
      [[Pt(C(6)F(5))(2)](2)(mu-SH)(mu-pz)](2-), respectively. The monomeric
      hydrosulfido complexes [M(C(6)F(5))(2)(SH)(PPh(3))](-) (M = Pd, Pt) have been
      prepared by reactions of the corresponding binuclear hydrosulfido complexes
      [M(2)(C(6)F(5))(4)(mu-SH)(2)](2-) with PPh(3) in the molar ratio 1:2, and they
      can be used as metalloligands toward Ag(PPh(3))(+) to form the heterodinuclear
      complex [(C(6)F(5))(2)(PPh(3))[S(H)AgPPh(3)]], and toward Au(PPh(3))(+) yielding
      the heterotrinuclear complexes [M(C(6)F(5))(2)(PPh(3))[S(AuPPh(3))(2)]]. The
      crystal structures of [NBu(4)](2)[[Pt(C(6)F(5))(2)(mu-SH)](2)],
      [Pt(C(6)F(5))(2)(PPh(3))[S(H)AgPPh(3)]], and
      [Pt(C(6)F(5))(2)(PPh(3))[S(AuPPh(3))(2)]] have been established by X-ray
      diffraction and show no short metal-metal interactions between the metallic
      centers.

PMID- 11578180
TI  - Synthesis and characterization of the largest isolated clusters of tin, [Sn12](12
      ), in (AE)Na10Sn12 (AE = Ca or Sr).
AB  - Reported are two isostructural Zintl compounds, CaNa(10)Sn(12) and
      SrNa(10)Sn(12), with mixed alkali and alkaline-earth cations and isolated
      clusters of Sn(12)(12-) with the shape of giant truncated tetrahedra. The
      compounds were synthesized by heating the corresponding mixtures of elements at
      950 degrees C. The structures were solved and refined from single-crystal X-ray
      diffraction data in the cubic space group I43m (No. 217), where Z = 2 with a =
      11.1847(6) and 11.2176(4) A for CaNa(10)Sn(12) and SrNa(10)Sn(12), respectively.
      Both compounds are diamagnetic and therefore electronically balanced.

PMID- 11578181
TI  - Nb(9)PdAs(7): a unique arrangement in the M(n2+3n+2)X(n2+n)Y family of hexagonal
      structures.
AB  - The ternary transition-metal arsenide Nb(9)PdAs(7) has been prepared through
      reaction of the elements, and its structure has been determined by single-crystal
      X-ray diffraction methods. It adopts a new structure type (Pearson symbol hP51,
      hexagonal, space group P6, Z = 3), with unit cell parameters a = 16.6955(6) and c
      = 3.5582(1) A. The structure contains assemblies of As-centered trigonal prisms
      that extend as triangular columns through sharing of the triangular faces. Not
      only does Nb(9)PdAs(7) extend a family of hexagonal structures with general
      formula M(n2+3n+2)X(n2+n)Y to n = 4, the highest member known thus far, but it
      also displays the unique feature in which there are two distinct types of
      triangular columns, one having corner atoms (Pd) different from the other atoms
      (Nb). Structural relationships between members of the M(n2+3n+2)X(n2+n)Y family
      are presented. The chemical bonding in Nb(9)PdAs(7) was analyzed through an
      extended Huckel band structure calculation.

PMID- 11578182
TI  - Dye sensitization of nanocrystalline titanium dioxide with square planar
      platinum(II) diimine dithiolate complexes.
AB  - A series of platinum-based sensitizers of the general type Pt(NN)(SS), where NN
      is 4,4'-dicarboxy-2,2'-bipyridine (dcbpy) or 4,7-dicarboxy-1,10-phenanthroline
      (dcphen) and SS is ethyl-2-cyano-3,3-dimercaptoacrylate (ecda), quinoxaline-2,3
      dithiolate (qdt), 1,2-benzenedithiolate (bdt), or 3,4-toluenedithiolate (tdt),
      that have various ground-state oxidation potentials has been synthesized and
      anchored to nanocrystalline titanium dioxide electrodes for light-to-electricity
      conversion in regenerative photoelectrochemical cells with an I(-)/I(-)(3)
      acetonitrile electrolyte. The intense mixed-Pt/dithiolate-to-diimine charge
      transfer absorption bands in this series could be tuned from 440 to 580 nm by
      choosing appropriate dithiolate ligands, and the highest occupied molecular
      orbitals varied by more than 500 mV. Spectrophotometric titration of the
      Pt(dcphen)(bdt) complex exhibits a ground-state pK(a) value of 3.2 +/- 0.1, which
      can be assigned to the protonation of the carboxylate group of the dcphen ligand.
      Binding of Pt(dcbpy)(qdt) to porous nanostructured TiO(2) films was analyzed
      using the Langmuir adsorption isotherm model, yielding an adsorption equilibrium
      constant of 4 x 10(5) M(-1). The amount of dye adsorbed at the surface of TiO(2)
      films was 9.5 x 10(-8) mol/cm(2), which is ca. 50% lower than the full monolayer
      coverage. The resulting complexes efficiently sensitized TiO(2) over a notably
      broad spectral range and showed an open-circuit potential of ca. 600 mV with an
      impressive fill factor of > 0.70, making them attractive candidates for solar
      energy conversion applications. The visible spectra of the 3,4-toluenedithiol
      based sensitizers showed an enhanced red response, but the lower photocurrent
      efficiency observed for these sensitizers stems in part from a sluggish halide
      oxidation rate and a fast recombination of injected electrons with the oxidized
      dye.

PMID- 11578183
TI  - Synthesis and characterization of fluorinated metal arsenates with a layer
      structure: (C4H12N2)(1.5)[M3F5(HAsO4)2(AsO4)] (M = Fe, Ga).
AB  - Two fluorinated metal arsenates,
      (C(4)H(12)N(2))(1.5)[M(3)F(5)(HAsO(4))(2)(AsO(4))] (M = Fe, Ga), have been
      synthesized under hydrothermal conditions and characterized by single-crystal X
      ray diffraction, magnetic susceptibility, Mossbauer spectroscopy, and (71)Ga NMR
      spectroscopy. The two compounds are isostructural and crystallize in the
      monoclinic space group P2(1)/c (No. 14) with a = 8.394(1) A, b = 21.992(3) A, c =
      10.847(1) A, beta = 96.188(2) degrees, and Z = 4 for the Fe compound, and a =
      8.398(1) A, b = 21.730(3) A, c = 10.679(1) A, beta = 95.318(2) degrees, and Z = 4
      for the Ga compound. The structure consists of infinite chains of corner-sharing
      MX(6) (X = O, F) octahedra and dimers of edge-sharing MO(3)F(3) octahedra, which
      are linked into two-dimensional sheets through arsenate tetrahedra with
      diprotonated piperazinium cations between the sheets. Magnetic susceptibility and
      Mossbauer spectroscopy confirm the presence of Fe(III). The (71)Ga MAS NMR
      spectrum clearly shows a line shape consisting of three components, corresponding
      to three crystallographically distinct Ga sites.

PMID- 11578184
TI  - 4-Cyanopyridine and amide-N and amide-O linkage isomers of 4-pyridinecarboxamide
      on trans-chloro(1,4,8,11-tetraazacyclotetradecane)ruthenium(II/III).
AB  - The synthesis, UV-vis spectra, and electrochemical behavior of the nitrile-bonded
      trans-[Ru(II)Cl(cyclam)(4-NCpyH(+))](BF(4))(2) (4-Ncpy = 4-cyanopyridine; cyclam
      = 1,4,8,11-tetraazacyclotetradecane) and of trans-[Ru(III)Cl(cyclam)(NHC(O)-4
      pyH(+))](2+) are described. The UV-vis spectrum of the Ru(II) nitrile complex
      shows a MLCT band at 548 nm at pH 1, which is shifted to 440 nm at pH
      approximately 6, for the unprotonated species. trans-[Ru(II)Cl(cyclam)(4
      NCpyH(+))](2+) was electrolytically oxidized (+600 mV vs Ag/AgCl) at pH 1 to
      Ru(III), followed by hydrolysis (k = 0.25 s(-1)) of the coordinated nitrile to
      give trans-[Ru(III)Cl(cyclam)(NHC(O)-4-pyH(+))](2+), in which the amide is
      deprotonated and coordinated through nitrogen. The identity of the species is pH
      dependent, the nitrogen-bonded amide prevailing at low pH (< 7), but the oxygen
      bonded amide is formed through linkage isomerization at higher pH (>8). Reduction
      of trans-[Ru(III)Cl(cyclam)(NHC(O)-4-pyH)](2+) in acidic media does not result in
      fast aquation (k = approximately 2.4 x 10(-5) s(-1)) as for other amides on
      ruthenium(II) pentaammine, but instead linkage isomerization occurs, resulting in
      the oxygen-bonded species, with an estimated rate constant of approximately 2 x
      10(-2) s(-1), smaller than in the pentaammine analogues.

PMID- 11578185
TI  - Relative binding energies of gas-phase pyridyl ligand/metal complexes by energy
      variable collisionally activated dissociation in a quadrupole ion trap.
AB  - The relative binding energies of a series of pyridyl ligand/metal complexes of
      the type [M(I)L(2)](+) and [M(II)L(3)](2+) are investigated by using energy
      variable collisionally activated dissociation in a quadrupole ion trap mass
      spectrometer. The pyridyl ligands include 1,10-phenanthroline and various
      alkylated analogues, 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine, and
      2,2':6',2' '-terpyridine, and the metal ions include cobalt, nickel, copper,
      zinc, cadmium, calcium, magnesium, lithium, sodium, potassium, rubidium, and
      cesium. The effect of the ionic size and electronic nature of the metal ion and
      the polarizability and degree of preorganization of the pyridyl ligands on the
      threshold activation voltages, and thus the relative binding energies of the
      complexes, are evaluated. Correlations are found between the binding constants of
      [M(II)L(3)](2+) complexes in aqueous solution and the threshold activation
      voltages of the analogous gas-phase complexes determined by collisionally
      activated dissociation.

PMID- 11578186
TI  - Ligand-field analysis of an Er(III) complex with a heptadentate tripodal N4O3
      ligand.
AB  - Polarized absorption and emission spectra of trigonal single crystals of an
      Er(III) complex coordinated to a heptadentate tripodal ligand are reported at
      temperatures between 8 and 298 K. The assigned energy levels below the onset of
      ligand absorption (< 25 000 cm(-1)) are fitted to a parametrized electronic
      Hamiltonian. The C(3) site symmetry of the Er(III) ion requires eight parameters
      for a full description of the ligand field within a one-electron operator
      description. This compound shows unusually large splittings of the multiplets,
      and the fitted parameters imply that this heptadentate ligand imparts the largest
      ligand field reported for an Er(III) complex. The ligand field was also
      interpreted within the angular overlap model (AOM). We derive the AOM matrix to
      include both sigma and anisotropic pi bonding and show that a useful description
      of the C(3) ligand field can be made using only five parameters. The success of
      the AOM description is encouraging for applications on isomorphous complexes
      within the lanthanide series and in describing the ligand field of low-symmetry
      complexes with less parameters than in the usual spherical harmonic expansion.

PMID- 11578187
TI  - Conversion of azomethine moiety to carboxamido group at cobalt(III) center in
      model complexes of Co-containing nitrile hydratase.
AB  - The Co(III) complex of the Schiff base ligand N-2-mercaptophenyl-2'-pyridylmethyl
      enimine (PyASH), namely, [Co(PyAS)(2)]Cl (1), has been synthesized via an
      improved method and its structure has been determined by X-ray crystallography.
      The two deprotonated ligands are arranged in mer configuration around the Co(III)
      center and the overall coordination geometry is octahedral. The coordinated
      azomethine function in 1 is rapidly converted into carboxamido group upon
      reaction with OH(-). The product is the bis carboxamido complex
      (Et(4)N)[Co(PyPepS)(2)] (2), reported by us previously. Reaction of H(2)O(2) with
      1 in DMF affords [Co(PyASO(2))(PyPepSO(2))] (3), a species with mixed imine and
      carboxamido-N donor centers as well as S-bound sulfinates. Further reaction with
      H(2)O(2) in the presence of NaClO(4) converts 3 into the previously reported bis
      carboxamido/sulfinato complex Na[Co(PyPepSO(2))(2)] (4). The reaction conditions
      for the various transformation reactions for complexes 1-4 and the structure of 3
      are also reported. The mechanism of the -CH=NR + [O] --> -C(=O)NHR transformation
      has been discussed. The reactions reported here provide convenient alternate
      routes for the syntheses of Co(III) complexes with coordinated carboxamide,
      thiolate, and/or sulfinate donors as models for the Co-site in the Co-containing
      nitrile hydratase(s).

PMID- 11578188
TI  - Luminescent alkynyl platinum-cadmium complexes: structural characterization of an
      unusual decanuclear cluster.
AB  - The reaction of (NBu(4))(2)[Pt(C triple bond CPh)(4)] with Cd(ClO(4))(2).6H(2)O
      in a 1:1 molar ratio yields a white solid [PtCd(C triple bond CPh)(4)](n) 1 (75%
      yield) together with yellow crystals of a very unusual decanuclear platinum
      cadmium cluster [Pt(4)Cd(6)(C triple bond CPh)(4)(mu-C triple bond CPh)(12)(mu(3)
      OH)(4)] 2 in low yield. Slow diffusion of acetonic solutions of the starting
      materials under aerobic conditions only produces crystals of 2 which have been
      shown by an X-ray analysis to be composed of a big hexanuclear cation
      [Cd(6)(mu(3)-OH)(4)](8+) and four [Pt(C triple bond CPh)(4)](2-) anions, held
      together by Pt.Cd and pi.Cd acetylide interactions. On the other hand, treatment
      of the insoluble product 1 with 1 equiv of NBu(4)X yields tetranuclear mixed
      metal soluble complexes (NBu(4))(2)[[Pt(mu-C triple bond CPh)(4)](2)(CdX)(2)] (X
      = Cl A, Br 3, CN 4), which contain two platinate fragments connected by two CdX
      units through Pt.Cd and mainly Cd.C(alpha) interactions. All complexes are
      strongly emissive in the solid state at room temperature.

PMID- 11578189
TI  - Use of SDS micelles to stabilize a ternary intermediate in the reaction of
      ferrioxamine B and 1,10-phenanthroline.
AB  - Spectrophotometric measurements of the reaction of ferrioxamine B (FeHDFB(+))
      with 1,10-phenanthroline (phen) reveal the presence of a ternary intermediate
      complex in both aqueous solution and an aqueous solution of 0.16 M sodium dodecyl
      sulfate (SDS). The stoichiometry of the intermediate is Fe(H(2)DFB)(phen)(2+) on
      the basis of a Schwarzenbach analysis of spectrophotometric data obtained at
      variable pH and phen concentrations. The ternary complex formation constant for
      the reaction FeHDFB(+) + H(+) + phen right arrow over left arrow
      Fe(H(2)DFB)(phen)(2+) is log K = 6.96 in aqueous solution and log K = 8.64 in
      aqueous 0.16 M SDS. The enhanced stability of Fe(H(2)DFB)(phen)(2+) in micellar
      solution was analyzed in terms of the pseudophase ion-exchange (PPIE) model of
      micellar reactions. The association constants for the binding of each reactant to
      the micellar pseudophase were measured by ultrafiltration. According to PPIE
      model calculations, the enhanced stability of Fe(H(2)DFB)(phen)(2+) in micellar
      SDS arises from a proximity effect created by the high local concentrations of
      reactants in the micellar pseudophase. The calculations also indicate that an
      inhibitory medium or compartmentalization effect is operative since the observed
      micellar enhancement is much smaller than predicted by the PPIE model. The
      micellar stabilization of the Fe(H(2)DFB)(phen)(2+) intermediate and the overall
      conversion of FeHDFB(+) to Fe(phen)(3)(2+) are discussed as a possible model
      system for siderophore iron release in microbial organisms.

PMID- 11578190
TI  - Synthesis and luminescence spectroscopy of a series of [eta(5)-CpFe(CO)2]
      complexes containing 1,12-dicarba-closo-dodecaboranyl and -ylene ligands.
AB  - Three new cyclopentadienyliron dicarbonyl compounds, 1-[eta(5)-CpFe(CO)(2)]-1,12
      C(2)B(10)H(11), 1-[[eta(5)-CpFe(CO)(2)]-1,12-C(2)B(10)H(10)-12-yl](2)Hg, and 1,12
      [eta(5)-CpFe(CO)(2)](2)-1,12-C(2)B(10)H(10), composed of 1,12-dicarba-closo
      dodecaborane as a ligand precursor were synthesized and found to be luminescent.
      The uncoordinated 1,12-C(2)B(10)H(12) bridging ligand precursor is luminescent
      with a band maximum at 25180 cm(-1), while the iron complexes luminesce at lower
      energies in the range 13120-14210 cm(-1). The lowest energy excited electronic
      state in the iron complexes is assigned to a ligand field transition of the iron
      chromophore. Cyclic voltammetry of 1,12-[eta(5)-CpFe(CO)(2)](2)-1,12
      C(2)B(10)H(10) displays two discrete one-electron oxidations, and the
      luminescence maximum is red shifted from that observed in 1-[eta(5)-CpFe(CO)(2)]
      1,12-C(2)B(10)H(11). Both of these observations suggest that the iron-centered
      chromophores are weakly coupled. In contrast, the 1-[[eta(5)-CpFe(CO)(2)]-1,12
      C(2)B(10)H(10)-12-yl](2)Hg complex is uncoupled as is evident from the single
      oxidation process observed with cyclic voltammetry. The extinction coefficient of
      1,12-[eta(5)-CpFe(CO)(2)](2)-1,12-C(2)B(10)H(10) is six times that of 1-[eta(5)
      CpFe(CO)(2)]-1,12-C(2)B(10)H(11), while the extinction coefficient of 1-[[eta(5)
      CpFe(CO)(2)]-1,12-C(2)B(10)H(10)-12-yl](2)Hg is only twice that of 1-[eta(5)
      CpFe(CO)(2)]-1,12-C(2)B(10)H(11). These spectroscopic properties are explained in
      terms of two coupled antiparallel transition dipole moments.

PMID- 11578191
TI  - Novel seven coordination geometry of Sn(IV): crystal structures of
      phthalocyaninato bis(undecylcarboxylato)Sn(IV), its Si(IV) analogue, and
      phthalocyaninato bis(chloro)silicon(IV). The electrochemistry of the Si(IV)
      analogue and related compounds.
AB  - Three newly elucidated crystal structures of group IV phthalocyaninato complexes
      are reported, along with data for two further SiPc carboxylate complexes. In one
      of these crystal structures, bis(undecylcarboxylate)Sn(IV) phthalocyanine, the
      tin ion is seven coordinate, which is a unique finding for this atom in
      phthalocyanine ring coordination. Comparison of these structures with other group
      IV phthalocyaninato and related structures reveals differences, illustrating
      features significant in the chemistries of Si(IV) and Sn(IV) ions. These
      differences are thought to originate from their differing sizes and
      polarizabilities. The structures show that the Sn(IV) ion can only occupy an in
      plane location in the phthalocyaninato ring where it elongates toward the two
      axial ligands. When the axial ligands do not facilitate this elongation cis
      coordination is preferred and the Sn(IV) ion sits above the phthalocyaninato ring
      plane. In contrast, the Si(IV) structures, with smaller, harder (i.e., less
      polarizable) Si(IV) ions, are six coordinate with the Si(IV) ion in the
      phthalocyaninato ring plane in a distorted octahedral symmetry. The electronic
      spectra and cyclic voltammetry of some of the Si compounds indicate that on the
      electrode the oxidized/reduced species behave as though they are in a solid film,
      rather than a soluble freely diffusing species.

PMID- 11578192
TI  - Equilibrium and kinetic studies on the reactions of alkylcobalamins with cyanide.
AB  - Ligand substitution equilibria of different alkylcobalamins (RCbl, R = Me,
      CH(2)Br, CH(2)CF(3), CHF(2), CF(3)) with cyanide have been studied. It was found
      that CN(-) first substitutes the 5,6-dimethylbenzimidazole (Bzm) moiety in the
      alpha-position, followed by substitution of the alkyl group in the beta-position
      trans to Bzm. The formation constants K(CN) for the 1:1 cyanide adducts
      (R(CN)Cbl) were found to be 0.38 +/- 0.03, 0.43 +/- 0.03, and 123 +/- 9 M(-1) for
      R = Me, CH(2)Br, and CF(3), respectively. In the case of R = CH(2)CF(3), the 1:1
      adduct decomposes in the dark with CN(-) to give (CN)(2)Cbl. The unfavorable
      formation constants for R = Me and CH(2)Br indicate the requirement of very high
      cyanide concentrations to produce the 1:1 complex, which cause the kinetics of
      the displacement of Bzm to be too fast to follow kinetically. The kinetics of the
      displacement of Bzm by CN(-) could be followed for R = CH(2)CF(3) and CF(3) to
      form CF(3)CH(2)(CN)Cbl and CF(3)(CN)Cbl, respectively, in the rate-determining
      step. Both reactions show saturation kinetics at high cyanide concentration, and
      the limiting rate constants are characterized by the activation parameters: R =
      CH(2)CF(3), DeltaH = 71 +/- 1 kJ mol(-1), DeltaS = -25 +/- 4 J K(-1) mol(-1), and
      DeltaV = +8.9 +/- 1.0 cm(3) mol(-1); R = CF(3), DeltaH = 77 +/- 3 kJ mol(-1),
      DeltaS = +44 +/- 11 J K(-1) mol(-1), and DeltaV = +14.8 +/- 0.8 cm(3) mol(-1),
      respectively. These parameters are interpreted in terms of an I(d) and D
      mechanism for R = CH(2)CF(3) and CF(3), respectively. The results of the study
      enable the formulation of a general mechanism that can account for the
      substitution behavior of all investigated alkylcobalamins including coenzyme
      B(12).

PMID- 11578193
TI  - A combined theoretical and experimental study of the reaction products of laser
      ablated thorium atoms with CO: first identification of the CThO, CThO(-), OthCCO,
      OTh(eta(3)-CCO), and Th(CO)(n) (n = 1-6) molecules.
AB  - Laser-ablated thorium atoms have been reacted with CO molecules during
      condensation in excess neon. Absorptions at 617.7 and 812.2 cm(-1) are assigned
      to Th-C and Th-O stretching vibrations of the CThO molecule. Absorptions at
      2048.6, 1353.6, and 822.5 cm(-1) are assigned to the OThCCO molecule, which is
      formed by CO addition to CThO and photochemical rearrangement of Th(CO)(2). The
      OThCCO molecule undergoes further photoinduced rearrangement to OTh(eta(3)-CCO),
      which is characterized by C-C, C-O, and Th-O stretching vibrations at 1810.8,
      1139.2, and 831.6 cm(-1). The Th(CO)(n) (n = 1-6) complexes are formed on
      deposition or on annealing. Evidence is also presented for the CThO(-) and
      Th(CO)(2)(-) anions, which are formed by electron capture of neutral molecules.
      Relativistic density functional theory (DFT) calculations of the geometry
      structures, vibrational frequencies, and infrared intensities strongly support
      the experimental assignments. It is found that CThO is an unprecedented actinide
      containing carbene molecule with a triplet ground state and an unusual bent
      structure ( angleCThO = 109 degrees ). The OThCCO molecule has a bent structure
      while its rearranged product OTh(eta(3)-CCO) is found to have a unique exocyclic
      structure with side-bonded CCO group. We also find that both Th(CO)(2) and
      Th(CO)(2)(-) are, surprisingly, highly bent, with the angleC-Th-C bond angle
      being close to 50 degrees; the unusual geometries are the result of extremely
      strong Th-to-CO back-bonding, which causes significant three-centered bonding
      among the Th atom and the two C atoms.

PMID- 11578195
TI  - Diazo complexes of rhenium with phosphite ligands: facile synthesis of
      bis(dinitrogen) [Re(N2)(2)P4]BPh4 derivatives.

PMID- 11578194
TI  - Separation and photophysical properties of the deltadelta, lambdalambda,
      deltalambda, and lambdadelta stereoisomers of a dinuclear ruthenium(II) complex.

PMID- 11578196
TI  - An alkali metal-crown ether complex supported by a Keggin anion through the three
      terminal oxygen atoms in a single M3O13 triplet: synthesis and characterization
      of [[Na(dibenzo-18-crown-6)(MeCN)]3[PMo12O40]].

PMID- 11578197
TI  - The mixed polychalcogenorhenate(IV) anions [Re4Q4(S3)4(S4)2](4-) (Q = S, Te):
      syntheses and crystal structures of [NMe4]5[Me2NH2]3[Re4Se4(S3)4(S4)2](2)*2.25H2O
      and [NH4]4[Re4Te4(S3)4(S4)2]*8H2O.

PMID- 11578198
TI  - Cooperative ratiometric chemosensors: pinwheel receptors with an integrated
      fluorescence system.
AB  - The synthesis and fluorescent properties of a second generation cooperative
      chemical sensor are described. The sensor has two interacting binding pockets for
      cooperative recognition of two analytes. Cooperative binding activates a
      ratiometric fluorescent response via formation of an excimer. Binding was
      characterized by NMR, absorption, and fluorescence spectroscopy. The advantages
      of separating the recognition elements from the fluorescent response elements are
      discussed.

PMID- 11578200
TI  - Heterobuckybowls: a theoretical study on the structure, bowl-to-bowl inversion
      barrier, bond length alternation, structure-inversion barrier relationship,
      stability, and synthetic feasibility.
AB  - Hybrid density functional theory (DFT) calculations at the B3LYP/cc-pVDZ level
      have been performed on a series of heterobuckybowls, 3X, C(18)X(3)H(6) (X = O,
      NH, CH(2), BH, S, PH, PH(3), Si, SiH(2), and AlH). The minimum energy
      conformations and the transition states for bowl-to-bowl inversion, where the
      geometry is bowl shaped, are computed and characterized by frequency
      calculations. The geometries of heterotrindenes, 2X, C(12)X(3)H(6) (X = O, NH,
      CH(2), BH, S, PH, PH(3), Si, SiH(2), and AlH), were obtained, and the bond length
      alternation (Delta) in the central benzenoid ring shows remarkable sensitivity as
      a function of substituent with a wide range of fluctuations (-0.014 to +0.092 A).
      The Delta computed in 2BH was found to be comparable with the highest bond
      alternation reported to date in benzenoid frameworks. The inversion dynamics of
      these heterobowls and their bowl depths were fit to a mixed quartic/quadratic
      function. The size of the heteroatom seems to exclusively control the bowl depth
      and rigidity as well as the synthetic feasibility. In contrast, the bond length
      alternation seems to be controlled by electronic factors and not by the size of
      the substituted atom either in trindenes or in heterosumanenes. The thermodynamic
      stability of this class of compounds is very much comparable with trithiasumanene
      (3S), which has been synthesized recently. The chemical hardness (eta) was
      measured to assess the stability of the heterosumanenes. The strain energy
      buildup in a sequential ring closure strategy along two synthetic routes, namely
      a triphenylene route and a trindene route, were explored, and the trindene route
      was found to be highly favorable for making such compounds compared to the
      triphenylene route. However, in both routes the ease of the synthetic feasibility
      increases as the size of the heteroatom increases.

PMID- 11578199
TI  - Design and synthesis of porphyrins bearing rigid hydrogen bonding motifs: highly
      versatile building blocks for self-assembly of polymers and discrete arrays.
AB  - Two aldehydes, 2,6-diacetamido-4-formylpyridine (7) and 1-butyl-6-formyluracil
      (11), are used to synthesize five pyridyl and four uracyl meso-subsituted
      porphyrins. With these complementary porphyrin building blocks, it is possible to
      build various types of multi-porphyrin supramolecules with different spatial
      relationships in predefined geometries. The formation and properties of self
      complementary dimers and a closed tetrameric square are presented as a basis of
      comparison to the latter system in the solid state. An X-ray structure of 5,10
      bis(4-tert-butylphenyl)-15,20-bis(3,5-diacetamido-4-pyridyl)porphyrin confirms
      its molecular structure and reveals a hydrogen-bonded supramolecular organization
      mediated by water molecules.

PMID- 11578201
TI  - Iron(II)-induced degradation of antimalarial beta-sulfonyl endoperoxides:
      evidence for the generation of potentially cytotoxic carbocations.
AB  - Reactions of antimalarial beta-sulfonyl endoperoxides 9 and 10, which, like
      yingzhaosu A (2), derive from the 2,3-dioxabicyclo[3.3.1]nonane system 3, with
      iron(II) salts were studied. Product analysis of the iron(II)-induced
      degradations provided evidence for the intermediacy of carbon-centered cyclohexyl
      radicals 20 and 31 and their possible oxidation to the corresponding carbocations
      21 and 32. It is conceivable that the antimalarial activity of beta-sulfonyl
      endoperoxides of type 5 may derive from alkylation of vital intraparasitic
      biomolecules by free radicals and/or carbocations, generated within the malaria
      parasite through a similar iron(II)-induced degradation process.

PMID- 11578202
TI  - Urethane N-carboxyanhydrides from beta-amino acids.
AB  - A general method has been developed for the synthesis of N-tert-butyloxycarbonyl
      N-carboxyanhydrides from beta-amino acids using Vilsmeier complex. These beta
      UNCA are stable, and the reactivity with different nucleophiles (alcohol, amine,
      lithium enolate) was studied.

PMID- 11578203
TI  - Palladium(II)-catalyzed synthesis of alpha-alkylidene-gamma-butyrolactams from N
      allylic 2-alkynamides. Total synthesis of (+/-)-isocynodine and (+/-)
      isocynometrine.
AB  - An efficient method for preparing alpha-alkylidene-gamma-butyrolactams via the
      Pd(II)-catalyzed cyclization of acyclic N-allylic 2-alkynamides via
      halopalladation, intramolecular olefin insertion, and beta-heteroatom elimination
      was developed. The reaction is less influenced by the leaving group and the
      concentration of the halide ions in comparison with the cyclization of acyclic
      alkynoates. The total syntheses of (+/-)-isocynodine and (+/-)-isocynometrine
      were realized using this method.

PMID- 11578204
TI  - Estimation of electron transfer parameters from AM1 calculations.
AB  - The utility of AM1 calculations for estimation of the electron-transfer
      parameters lambda'(v) (the enthalpy part of the Marcus internal reorganization
      energy) and H(ab) (the electronic coupling between the charge-bearing units) is
      considered for some charge-localized intervalence bis(hydrazine) radical cations,
      for which these parameters have been experimentally determined from optical
      measurements. The Koopmans estimate of lambda'(v) that employs the orbital
      separation for the neutral compound at the radical cation geometry is far from
      that calculated from the enthalpies of the species involved (eq 1) and is not
      correct. The eq 1 lambda'(v) enthalpies estimated by AM1 are reasonably good for
      compounds with only alkyl substituents but are overestimated by 33-59% for aryl
      substituted hydrazines. The Koopmans estimate of H(ab) as half the orbital
      separation for the neutral species at the transition state geometry requires
      adjustment for the twist angles to those of the relaxed ground state to produce
      useful H(ab) values. Symmetry breaking occurs for the electron-transfer
      transition states of the compounds with saturated bridges, and the Koopmans
      estimate predicts H(ab) values that are slightly less than half as large as the
      optical measurements.

PMID- 11578205
TI  - Total synthesis of 2',3',4',5',5' '-(2)h(5)-ribonucleosides: the key building
      blocks for NMR structure elucidation of large RNA.
AB  - The diastereospecific chemical syntheses of uridine-2',3',4',5',5' '-(2)H(5)
      (21a), adenosine-2',3',4',5',5' '-(2)H(5) (21b), cytidine-2',3',4',5',5' '
      (2)H(5)(2)H(5) (21c), and guanosine-2',3',4',5',5' '-(2)H(5) (21d) (>97 atom %
      (2)H at C2', C3', C4', and C5'/C5' ') have been achieved for their use in the
      solution NMR structure determination of oligo-RNA by the Uppsala "NMR-window"
      concept (refs 4a-c, 5a, 6), in which a small (1)H segment is NMR-visible, while
      the rest is made NMR-invisible by incorporation of the deuterated blocks 21a-d.
      The deuterated ribonucleosides 21a-d have been prepared by the condensation of
      appropriately protected aglycone with 1-O-acetyl-2,3,5-tri-O-(4-toluoyl)
      alpha/beta-D-ribofuranose-2,3,4,5,5'-(2)H(5) (19), which has been obtained via
      diastereospecific deuterium incorporation at the C2 center of appropriate D
      ribose-(2)H(4) derivatives either through an oxidation-reduction-inversion
      sequence or a one-step deuterium-proton exchange in high overall yield (44% and
      24%, respectively).

PMID- 11578206
TI  - Kinetic study of the phenolysis of bis(4-nitrophenyl) carbonate, bis(4
      nitrophenyl) thionocarbonate, and methyl 4-nitrophenyl thionocarbonate.
AB  - The reactions of a homogeneous series of phenols with bis(4-nitrophenyl)
      carbonate (BNPC), bis(4-nitrophenyl) thionocarbonate (BNPTOC), and methyl 4
      nitrophenyl thionocarbonate (MNPTOC) are subjected to a kinetic investigation in
      water, at 25.0 degrees C and ionic strength of 0.2 M (KCl). Under excess of
      phenol over the substrate, all the reactions obey pseudo-first-order kinetics and
      are first order in phenoxide anion. The reactions of BNPC show a linear Bronsted
      type plot with slope beta = 0.66, consistent with a concerted mechanism (one
      step). In contrast, those of BNPTOC and MNPTOC show biphasic Bronsted-type plots
      with slopes beta = 0.30 and 0.44, respectively, at high pK(a), and beta = 1.25
      and 1.60, respectively, at low pK(a), consistent with stepwise mechanisms. For
      the reactions of both thionocarbonates, the pK(a) value at the center of the
      Bronsted plot (pK(a)(0)) is 7.1, which corresponds to the pK(a) of 4-nitrophenol.
      This confirms that the phenolyses of the thionocarbonates are stepwise processes,
      with the formation of an anionic tetrahedral intermediate. By the comparison of
      the kinetics and mechanisms of the title reactions with similar reactions, the
      following conclusions can be drawn: (i) Substitution of S(-) by O(-) in an
      anionic tetrahedral intermediate (T(-)) destabilizes it. (ii) The change of MeO
      by 4-nitrophenoxy in T(-) results in an increase of both the rate constant and
      equilibrium constant, for the formation of T(-), and also in an enlargement of
      the rate coefficient for the expulsion of 4-nitrophenoxide from T(-). (iii)
      Substitution of an amino group in a tetrahedral intermediate by ArO destabilizes
      it. (iv) Secondary alicyclic amines and other amines show greater reactivity
      toward MNPTOC than isobasic phenoxide anions.

PMID- 11578208
TI  - Synthesis and mechanistic study of fused 2-pyrrolines via thermolysis of 6
      substituted-3,5-hexadienyl azidoformates.
AB  - Thermolysis of 3,5-hexadienyl azidoformates at 300 degrees C, 0.05 Torr, led to a
      fused 2-pyrroline regiospecifically, regardless of the configuration E or Z
      between the C-3 and C-4 double bond. Thermolysis of 6-substituted-3,5(E)
      hexadienyl azidoformates yielded a kinetically controlled 2-pyrroline with cis
      configuration between H-1 and H-8a whereas 6-substituted-3,5(Z)-hexadienyl
      azidoformates produced a cis and trans mixture. The mechanism was proposed as the
      loss of nitrogen to form an acyl nitrene, then addition to a double bond to
      produce an aziridine. Finally the cleavage of the C-C bond generated a
      vinylazomethine ylide followed by recyclization to a fused 2-pyrroline.

PMID- 11578207
TI  - Heterocyclization of functionalized vinylic derivatives of imidazo.
AB  - Heterocyclization of functionalized vinylic derivatives of imidazo[1,2
      a]pyridines was explored experimentally and theoretically using semiempirical AM1
      and ab initio methods. A range of functionalized vinylic derivatives (azido,
      amino, and carbodiimide groups) were prepared for conversion into
      pyrroloazaindoles 19-22, imidazo[1,x]-, (x = 5, 6, 7, 8), [2,6]-, and
      [2,7]naphthyridines 28-30, 35-38 by thermal reaction. In the case of vinylic
      groups in the 5 position, peri annulation also was observed. The experimental and
      theoretical data are compared and discussed.

PMID- 11578209
TI  - Catalytic asymmetric cyclopropanation of heteroaryldiazoacetates.
AB  - Rh(2)(S-DOSP)(4)-catalyzed decomposition of heteroaryldiazoacetates in the
      presence of styrene results in highly diastereoselective and enantioselective
      cyclopropanations. Heteroaryldiazoacetates containing both electron-rich and
      electron-deficient heterocycles, such as thiophene, furan, pyridine, indole,
      oxazole, isoxazole, and benzoxazole, are effective in this chemistry. These
      studies broaden the range of diazo compounds containing both electron-withdrawing
      and electron-donating groups, which undergo highly diastereoselective
      cyclopropanations.

PMID- 11578210
TI  - Synthesis and comparative study on the reactivity of peptidyl-type phosphinic
      esters: intramolecular effects in the alkaline and acidic cleavage of methyl beta
      carboxyphosphinates.
AB  - Using the phosphinic analogue of Cbz-Phe-Gly-OEt 1a as a template for this study,
      several phosphinic esters (2a-g) were prepared, employing an efficient method for
      each case. The reactivity of these derivatives under conventional deprotection
      conditions was studied, and the results are listed comparatively. The effect of
      steric hindrance as well as the contribution of neighboring groups in the rate of
      hydrolysis of suitably selected beta-carboxyphosphinates under acidic and
      alkaline deprotection conditions was examined. The results clearly demonstrate
      that a significant acceleration of phosphinate cleavage occurs due to the
      intermediacy of a five-membered, mixed anhydride-type species. This was supported
      by the observation that similar interactions were not observed in the case of
      hindered alpha-carboxyphosphinate homologous derivatives.

PMID- 11578211
TI  - Thermal reduction of 7H-benz[d,e]anthracen-7-one and related ketones under
      hydrogen-transfer conditions.
AB  - In the presence of hydrogen donor solvents and at elevated temperatures, aromatic
      ketones can be selectively deoxygenated to the corresponding hydroaromatic
      compounds. The kinetics for reduction of 7H-benz[d,e]anthracen-7-one
      (benzanthrone, 6) into 7H-benz[d,e]anthracene (benzanthrene, 1) in 9,10
      dihydroanthracene (3) solvent has been investigated in detail. The relatively
      slow hydrogenation of 6 is due to reversibility of the initial hydrogen-transfer
      step according to a reverse radical disproportionation (RRD). The dynamics could
      well be rationalized using the energetics of species computed by density
      functional theory (DFT). The application of hydrogen donors such as 1 as a
      hydrogen-transfer agent, although favorable in terms of a low benzylic carbon
      hydrogen bond dissociation enthalpy, is limited due to the slow self
      hydrogenation, which in case of 1 gives 5,6-dihydro-4H-benz[d,e]anthracene (7).

PMID- 11578212
TI  - Pd(ii)-hydrotalcite-catalyzed oxidation of alcohols to aldehydes and ketones
      using atmospheric pressure of air.
AB  - A heterogenized Pd catalyst, Pd(II)-hydrotalcite (palladium(II) acetate-pyridine
      complex supported by hydrotalcite) catalyzes the aerobic oxidation in toluene of
      a variety of primary and secondary alcohols into the corresponding aldehydes and
      ketones in high yields using atmospheric pressure of air as a sole oxidant under
      mild conditions. This catalyst is also effective for the oxidation of allylic
      alcohols, especially such as geraniol and nerol, without any isomerization of an
      alkenic part. The catalyst can be easily prepared from all commercially available
      reagents and reused several times.

PMID- 11578213
TI  - Celogentins A-C, new antimitotic bicyclic peptides from the seeds of Celosia
      argentea.
AB  - Three new bicyclic peptides, celogentins A (1), B (2), and C (3), have been
      isolated together with a known-related peptide, moroidin (4), from the seeds of
      Celosia argentea, and their structures including absolute stereochemistry were
      determined by using extensive NMR methods and chemical means. Celogentins A (1),
      B (2), and C (3) inhibited the polymerization of tubulin, and celogentin C (3)
      was four times more potent than moroidin (4) in the inhibitory activity.
      Structure-activity relationship study using moroidin derivatives 5-7 and analogue
      8 as well as celogentins A-C (1-3) and moroidin (4) indicates that the bicyclic
      ring system including unusual non-peptide connections among beta(s)-Leu, Trp, and
      His residues characteristic of celogentins and moroidin, with ring size and
      conformations suitable for interaction with tubulin would be important for their
      biological activity.

PMID- 11578214
TI  - Palladium-catalyzed synthesis of 2,3-dihydro-2-ylidene-1,4-benzodioxins.
AB  - Palladium-catalyzed condensation of benzene-1,2-diol with various propargylic
      carbonates afforded regio- and stereoselectively 2,3-dihydro-2-ylidene-1,4
      benzodioxins. The reaction is suggested to proceed by the formation of a (sigma
      allenyl)palladium complex, followed by the intermolecular attack of the phenoxide
      ion on this complex to generate a new (sigma-allyl)palladium complex in
      equilibrium with the corresponding (eta(3)-allyl)palladium complex.
      Intramolecular attack of the phenoxide ion afforded the corresponding benzodioxan
      compound. This last attack occurs predominantly at the more electrophilic end of
      the (eta(3)-allyl)palladium intermediate. The Z- or E-stereochemistry of the
      products was established by (1)H NMR and proton NOE measurements and also by X
      ray analysis on an example. The Z-stereochemistry generally observed is in
      agreement with the formation of this (eta(3)-allyl)palladium intermediate.
      However, in the case of tertiary propargylic carbonates, the E-stereochemistry
      generally observed could be explained by an intramolecular attack of the
      phenoxide ion on the intermediate (sigma-allyl)palladium complex, in slow
      equilibrium with the (eta(3)-allyl)palladium complex.

PMID- 11578215
TI  - Intramolecular behaviors of anthryldicarbenic systems: dibenzo[b,f]pentalene and
      1H,5H-dicyclobuta[de,kl]anthracene.
AB  - 9,10-Bis[methoxy(trimethylsilyl)methyl]anthracenes (24), synthesized from 9,10
      dilithioanthracene (26) and bromomethoxytrimethylsilylmethane (27, 2 equiv),
      decompose (550-650 degrees C/10(-3) mmHg) carbenically to dibenzo[b,f]pentalene
      (28, > 48%). 9,10-Anthryldicarbenes 39 or their equivalents convert to pentalene
      28 rather than di-peri-cyclobutanthracenes 30 and 31, benzobiphenylene 32, or
      extended rearrangement products 33-38. Formation of 28 from 24 raises questions
      with respect to the behavior of 1,3,4,6-cycloheptatetraenyl-1-carbenes 49,
      2,4,5,7-cyclooctatetraenylidene 51, 2,5,7-cyclooctatriene-1,4-diylidene 52,
      1,2,4,5,7-cyclooctapentaene 53, and bicyclo[4.1.0]heptatrienyl-1-carbenes 54 and
      to carbon-skeleton and hydrogen rearrangements of anthryldicarbenes 39 and/or
      their equivalents at various temperatures. 1,5
      Bis[methoxy(trimethylsilyl)methyl]anthracenes (25), prepared from 1,5
      diiodoanthracene (63) and methoxytrimethylsilylmethylzinc bromide (57, 2 equiv)
      as catalyzed by PdCl(2)(PPh(3))(2), yield the di-peri-carbenic reaction product
      1H,5H-dicyclobuta[de,kl]anthracene (30, > 40%) on pyrolysis at 550-650 degrees
      C/10(-3) mmHg. Proof of structure and various aspects of the mechanisms of
      formation of 30 are discussed.

PMID- 11578216
TI  - Carbon-carbon bond formation of alkenylphosphonates by aldehyde insertion into
      zirconacycle phosphonates.
AB  - Ethyl 1-butynylphosphonate reacts with Cp(2)ZrCl(2)/2n-BuLi to give a three
      membered zirconacycle that readily inserts aldehydes. Hydrolysis of the
      intermediate five-membered zirconacycles leads to two products, 4 and 5. In the
      major product, 5, the aldehyde inserts into C2 of the zirconacycle, while in the
      minor product, 4, the aldehyde inserts into C1. Products 5 are obtained in 38-75%
      isolated yields. Products 4 are obtained in approximately 1-12%. Essentially,
      only compounds 5 are produced with ortho-substituted aldehydes. The regio- and
      stereochemistry of 4 and 5 were determined by (3)J(PH), (2)J(PC2), and (3)J(PC3)
      coupling constants.

PMID- 11578217
TI  - Parallel synthesis and evaluation of 132 (+)-1,2,9,9a
      tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) analogues of CC-1065 and the
      duocarmycins defining the contribution of the DNA-binding domain.
AB  - The solution-phase, parallel synthesis and evaluation of a library of 132 (+)
      1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) analogues of CC-1065 and
      the duocarmycins containing dimeric monocyclic, bicyclic, and tricyclic
      heteroaromatic replacements for the DNA-binding domain are described. This
      systematic study revealed clear trends in the structural requirements for
      observation of potent cytotoxic activity and DNA alkylation efficiency, the range
      of which spans a magnitude of > or =10 000-fold. Combined with related studies,
      these results highlight that the role of the DNA-binding domain goes beyond
      simply providing DNA-binding selectivity and affinity (10-100-fold enhancement in
      properties), consistent with the proposal that it contributes significantly to
      catalysis of the DNA alkylation reaction accounting for as much as an additional
      1000-fold enhancement in properties.

PMID- 11578218
TI  - Biradicals from benzoenyne-allenes. Application in the synthesis of 11H
      benzo[b]fluoren-11-ols, 1H-cyclobut[a]indenes, and related compounds.
AB  - New synthetic pathways to 11H-benzo[b]fluoren-11-ols, 1H-cyclobut[a]indenes, and
      related compounds via biradicals generated from benzoenyne-allenes were
      developed. Treatment of the diacetylenic propargylic alcohols 13, derived from
      condensation between benzophenones and the lithium acetylide of 1-(2
      ethynylphenyl)-2-phenylethyne, with thionyl chloride produced the 11-chloro-11H
      benzo[b]fluorene 14 and, after hydrolysis, the corresponding 11H-benzo[b]fluoren
      11-ols 15. The transformation involved a sequence of reactions, including a
      biradical-forming C2-C6 cyclization (Schmittel cyclization) reaction of the
      chlorinated benzoenyne-allene intermediates followed by an intramolecular radical
      radical coupling to form the formal Diels-Alder adducts. Interestingly, in the
      case of the diacetylenic propargylic alcohol 26, obtained from dibenzosuberenone
      (25), an intramolecular [2 + 2] cycloaddition reaction of the chlorinated
      benzoenyne-allene intermediate occurred, furnishing the 1H-cyclobut[a]indene 27
      exclusively. The dramatic change of the reaction pathway could be attributed to
      the emergence of a steric strain due to the nonbonded interactions with the
      chloro substituent along the pathway toward the formal Diels-Alder adduct 31. On
      the other hand, the non-chlorinated benzoenyne-allene, derived from prototropic
      isomerization of the diacetylenic hydrocarbon 60, underwent a formal Diels-Alder
      reaction to furnish the 11H-benzo[b]fluorene-type hydrocarbon 61 exclusively.

PMID- 11578219
TI  - Torquoselectivity induced by lone-pair conjugation in the electrocyclic reactions
      of 1-azapolyenes.
AB  - Torquoselectivity in the electrocyclic interconversions of 1-azapolyenes and
      their heterocyclic isomers was investigated theoretically. The ring openings of
      1,2-dihydroazete, 1,2-dihydropyridine, and 1,2-dihydroazocine were examined using
      HF, MP2, and B3LYP calculations. A large preference for inward rotation of the
      nitrogen lone pair and outward rotation of the N-H group was found for the four-
      and six-electron systems. No strong preference was observed for the eight
      electron system.

PMID- 11578220
TI  - Theoretical studies on cycloaddition reactions between keteniminium cations and
      olefins.
AB  - The mechanisms of seven reactions between keteniminium cations and olefins have
      been theoretically explored at BHandHLYP/6-31G level. It is found that these
      seven reactions always form a relatively stable hydrogen-bonded type of ion
      molecule complex first except for reactions 1d+2a and 1e+2a, which have no
      hydrogen atom attached to nitrogen atom in keteniminium cations. Some reactions
      take place via a concerted but unsynchronous mechanism, and the others are
      stepwise processes. The substituent effects are also studied. The data reveal
      that the electron-pushing substituents on keteniminium cations disfavor the
      reaction, and the electron-attracting substituents on keteniminium cations favor
      the reactions. The substituent effects on ethene are contrary to the former case.

PMID- 11578221
TI  - Conformational studies by dynamic NMR. 84.(1) structure, conformation, and
      stereodynamics of the atropisomers of N-aryl-tetrahydropyrimidines.
AB  - The existence of stereolabile atropisomers for a number of N-aryl
      tetrahydropyrimidines in solution has been deduced from the observation of the
      anisochronous NMR signals of prochiral methylene groups. The interconversion
      barriers for these atropisomers have been measured by line shape analysis of
      dynamic NMR spectra at various temperatures: a Molecular Mechanics modeling
      resulted in good agreement with these values. In an appropriate case, distinct
      NMR signals for the two enantiomeric forms could be observed at ambient
      temperature in a chiral environment. Evidence was also obtained for an exchange
      process occurring between two conformers experiencing a very biased equilibrium.
      Single-crystal X-ray diffraction of one such compound yielded a molecular
      structure in good agreement with the results obtained by ab initio calculations.

PMID- 11578222
TI  - Absolute configuration in 4-alkyl- and 4-aryl-3,4-dihydro-2(1H)-pyrimidones: a
      combined theoretical and experimental investigation.
AB  - Structural features (orientation of the carboxyl group, ring puckering),
      electronic absorption, and circular dichroism spectra of 4-alkyl- and 4-aryl
      dihydropyrimidones 1-5 are calculated by semiempirical (AM1, INDO/S), ab initio
      (HF/6-31G, CIS/6-31G, RPA/6-31G), and density functional theory (B3LYP/6-31G)
      methods. These calculations allow an assignment of the absolute configuration by
      comparison of simulated and experimental CD spectra. Although the ab initio
      methods greatly overestimate electronic transition energies, the general
      appearance of the experimental CD spectra is quite nicely reproduced by these
      calculations. Thus, comparison of experimental with calculated CD spectra is a
      reliable tool for the assignment of the absolute configuration. For 4-methyl
      derivatives 1, the first enantiopure DHPM examples with no additional aromatic
      substituent, the stereochemistry at C4 provided by the theoretical results is
      confirmed by X-ray structure determination of the diastereomeric salt 6.
      Additional support is the consistent HPLC elution order found for all
      investigated DHPMs on a cellulose-derived chiral stationary phase.

PMID- 11578223
TI  - Intercalation of multiple carbon atoms between the carbonyls of alpha-diketones.
AB  - The reaction of open-chain or cyclic alpha-diketones with specific omega-alkenyl
      organometallics leads readily under the proper conditions to 1,2-diols bonded to
      terminal olefinic chains. With 1-phenyl-1,2-propanedione, biacetyl, and
      cyclohexane-1,2-dione, allylindation in aqueous THF proceeds readily at both
      adjacent carbonyls. For cyclododecane-1,2-dione, recourse must be made to
      allylmagnesium bromide for completing the second-stage condensation. Grignard
      reagents have also served well as reactants for biacetyl monoadducts. In
      contrast, monoallylated camphorquinone is reluctant to couple to Grignard
      reagents and reacts only when Barbier-type alkyllithium reactions are applied.
      The ring closing metatheses of these products have been examined. Where six
      membered ring formation operates, cyclization can be performed directly on diols.
      When larger rings are involved, the diols will react only if structural
      preorganization capable of facilitating mutual approach of the two double bonds
      is at play. For this purpose, the prior conversion to a cyclic carbonate holds
      considerable utility. In the latter setting, saponification must precede the diol
      cleavage step which has been performed with lead tetraacetate. The latter reagent
      also exhibits the very beneficial effect of facilitating removal of ruthenium and
      phosphorus byproducts generated during the metathesis step. This chemistry
      conveniently lends itself to the controlled intercalation of multiple methylene
      groups between the carbonyl carbons of readily available alpha-diketones to
      deliver linear or cyclic products.

PMID- 11578224
TI  - Synthesis of (S)-isoprenoid thiodiphosphates as substrates and inhibitors.
AB  - Thiolo thiophosphate analogues of isopentenyl diphosphate (IPP), dimethylallyl
      diphosphate (DMAPP), geranyl diphosphate (GPP), farnesyl diphosphate (FPP), and
      geranylgeranyl diphosphate (GGPP) were synthesized. Inorganic thiopyrophosphate
      (SPP(i)) was prepared from trimethyl phosphate in four steps. The tris(tetra-n
      butylammonium) salt was then used to convert isopentenyl tosylate to (S)
      isopentenyl thiodiphosphate (ISPP). (S)-Dimethylallyl (DMASPP), (S)-geranyl
      (GSPP), (S)-farnesyl (FSPP), and (S)-geranylgeranyl thiodiphosphate (GGSPP) were
      prepared from the corresponding bromides in a similar manner. ISPP and GSPP were
      substrates for avian farnesyl diphosphate synthase (FPPase). Incubation of the
      enzyme with ISPP and GPP gave FSPP, whereas incubation with IPP and GSPP gave
      FPP. GSPP was a substantially less reactive than GPP in the chain elongation
      reaction and was an excellent competitive inhibitor, K(I)(GSPP) = 24.8 microM, of
      the enzyme. Thus, when ISPP and DMAPP were incubated with FPPase, GSPP
      accumulated and was only slowly converted to FSPP.

PMID- 11578225
TI  - Polyethylated aromatic rings: conformation and rotational barriers of
      1,2,3,4,5,6,7,8-octaethylanthracene, 1,2,3,4,6,7,8-heptaethylfluorene, and
      1,2,3,4,5,6,7,8-octaethylfluorene.
AB  - 1,2,3,4,5,6,7,8-Octaethylanthracene (5), 1,2,3,4,6,7,8-heptaethylfluorene (7),
      and 1,2,3,4,5,6,7,8-octaethylfluorene (8) were synthesized by Friedel-Crafts
      ethylations of 9,10-dihydroanthracene and fluorene. MM3 calculations indicate
      that the two ethylated six-membered rings of 5 and 7 are conformationally
      independent. According to the calculations, two low-energy conformers of each
      compound are possible with the ethyl groups attached to the external aryl rings
      arranged in an alternated "up-down" orientation. MM3 calculations indicate that
      in the lowest energy conformation the central fluorene core of 8 adopts a twisted
      conformation to avoid repulsive steric interactions between the ethyls at the bay
      region. Two fully alternated up-down conformations are possible for 8, differing
      in the orientation ("in" or "out") of the ethyls in the bay region. MM3
      calculations predict that the lowest energy conformer is the fully alternated
      "out" form of C(2)() symmetry. The rotational barriers of 5, 7, and 8 are in the
      8.7-11.3 kcal mol(-1) range, the largest barrier corresponding to the more
      crowded octaethylfluorene 8. Anthracene 5 adopts in the crystal a conformation of
      approximate C(2)(h) symmetry with pairs of peri groups on the same edge of the
      molecule oriented syn. The conformations adopted in the crystal by 7 and 8 do not
      correspond to the calculated lowest energy form. In the conformation of 7 in the
      crystal the ethyl groups on the trisubstituted ring adopt the unusual all syn
      arrangement. Octaethylfluorene 8 adopts a conformation with a twisted central
      fluorene core but with a syn arrangement of a pair of vicinal ethyl groups.

PMID- 11578226
TI  - C-H insertion approach to the synthesis of endo,exo-furofuranones: synthesis of
      (+/-)-asarinin, (+/-)-epimagnolin A, and (+/-)-fargesin.
AB  - A series of novel 5-aryl-4-aryloxymethyl-3-diazotetrahydrofuran-2-ones (12, 24,
      and 35a/b) have been prepared and found to undergo regio- and stereoselective C-H
      insertion reactions to afford 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane-8-ones
      (18, 26, and 36a/b) with endo,exo stereochemistry. Subsequent reduction of the
      lactone ring and cyclization of the resulting diols 27 and 37a/b permitted the
      synthesis of three endo,exo-furofuran lignans: asarinin (2), fargesin (3), and
      epimagnolin A (4). En route to the key diazo compounds 24 and 35a/b, a modified
      procedure for the Ghosez keteniminium-olefin cyclization was developed, which was
      required to minimize the decomposition of acid-sensitive functional groups such
      as electron-rich benzylic ethers that were present in the target compounds 2-4.

PMID- 11578227
TI  - A new route to hindered tertiary amines.
AB  - The Rh(2)(OAc)(4)-stabilized carbenoid derived from dimethyl diazomalonate has
      been found to insert into the N-H bond of sterically hindered secondary aliphatic
      amines to afford hindered tertiary aliphatic amines in quite satisfactory yields.
      For example dimethyl 2-(dicyclohexylamino)propanedioate was formed in 85% yield
      from dicyclohexylamine, and the severely hindered dimethyl 2-(2,2,6,6-tetramethyl
      1-piperidinyl)propanedioate was formed in 38% yield from 2,2,6,6
      tetramethylpiperidine. The Rh(2)(OAc)(4) - dimethyl diazomalonate reaction was
      found to work also for arylalkylamines and diarylamines. In these cases, small
      amounts of products resulting from formal insertion of the carbenoid into an
      aromatic C-H bond were detected. Substitution at ortho positions caused the yield
      of C-H insertion products to increase. Other diazo compounds, viz. ethyl
      diazoacetoacetate, 2-diazocyclohexane-1,3-dione, and 2-diazo-5,5
      dimethylcyclohexane-1,3-dione, performed satisfactorily in Rh(2)(OAc)(4)
      catalyzed reactions with arylalkylamines and diarylamines, but led to complicated
      reaction mixtures with dialkylamines.

PMID- 11578228
TI  - Efficient O-trimethylsilylation of alcohols and phenols with trimethylsilyl azide
      catalyzed by tetrabutylammonium bromide under neat conditions.
AB  - A very efficient procedure for the trimethylsilylation of a wide variety of
      alcohols, including primary, allylic, benzylic, secondary, hindered secondary,
      tertiary, and phenols is reported. The reactions were carried out under neat
      conditions with trimethylsilyl azide (TMSN(3)) and, when necessary, in the
      presence of a catalytic amount (20 mol %) of tetrabutylammonium bromide (TBABr)
      at 30 or 70 degrees C. Under catalytic conditions, the yields of the
      corresponding trimethylsilyl ethers were greater than 91%. This procedure also
      allows the selective protection of primary and secondary alcohols in the presence
      of tertiary ones.

PMID- 11578229
TI  - Donor and acceptor properties of the chromium tricarbonyl substituent in benzylic
      and homobenzylic anions, cations, and radicals.
AB  - Both benzylic cations and anions are strongly stabilized by chromium tricarbonyl
      complexation, while benzylic radicals are largely unaffected. Density functional
      theory calculations were performed on primary, secondary, and tertiary benzylic
      species to explore the effect of substitution on the stabilizing ability of the
      chromium tricarbonyl moiety. Complexed 1-indanyl species were also examined to
      elucidate the effect of conformational restraint. It was found that the strong
      stabilization of benzylic anions and the slight destabilization of benzylic
      radicals by chromium tricarbonyl are insensitive to skeletal changes. Chromium
      complexed benzylic cations, however, are highly sensitive to changes in the
      organic framework, with increased substitution or constriction of conformational
      mobility eroding the effect of the metal. 2-Indanyl species were also examined to
      study the effect of the chromium tricarbonyl fragment on homobenzylic species. It
      was found that the metal fragment stabilizes distant anions by field and
      inductive effects and cations by a direct interaction of the metal with the
      cationic carbon. Homobenzylic radicals, however, do not interact with the
      chromium tricarbonyl moiety and suffer a slight inductive destabilization.

PMID- 11578230
TI  - Triethylborane-initiated room temperature radical addition of hypophosphites to
      olefins: synthesis of monosubstituted phosphinic acids and esters.
AB  - A novel and practical approach to monosubstituted phosphinic acid
      (alkylphosphonous acid) derivatives from hypophosphite salts or esters is
      described. Phosphorus-centered radical formation is initiated with Et(3)B/O(2),
      and the reaction is conveniently conducted at room temperature in an open flask.
      In contrast to previously reported conditions for the radical reaction of
      hypophosphorous acid and sodium hypophosphite (peroxide initiators, acid
      catalysis, heat), the method proceeds under neutral conditions and therefore
      tolerates a wide range of functional groups. Previously inaccessible phosphinic
      acids can be prepared in a single step from cheap starting materials. Excellent
      selectivity is observed for monoaddition, and symmetrical dialkyl phosphinates do
      not form in significant amounts. Monosubstituted phosphinic acids are usually
      obtained in better than 90% purity by a simple extractive workup; however,
      isolated yields are diminished if the substituent is polar. Because radicals
      derived from hypophosphites are electrophilic, the reaction is limited to the use
      of electron-rich olefins. The reaction conditions can also be employed in the
      room temperature radical reduction of alkyl halides and provide an exceptionally
      mild and environmentally friendly alternative to the use of tributyltin hydride.
      The remarkable mild nature of the reaction conditions allows for the radical
      reaction of sensitive alkyl hypophosphites to occur, in which case, a catalytic
      amount of Et(3)B suffices to deliver alkyl phosphinate esters in reasonable
      yield.

PMID- 11578231
TI  - An enantioselective ketene-imine cycloaddition method for synthesis of
      substituted ring-fused 2-pyridinones.
AB  - Previously, a method for the stereoselective synthesis of beta-lactams, starting
      from 2H-Delta(2)-thiazolines and Meldrum's acid derivatives, has been reported
      from our laboratory. We now report a new method for the synthesis of optically
      active, highly substituted ring-fused 2-pyridinones. This was discovered when 2
      alkyl-Delta(2)-thiazolines and Meldrum's acid derivatives were treated with
      HCl(g) in benzene at 5 --> 78 degrees C. Further refinement of the synthetic
      protocol revealed that use of 1,2-dichloroethane as solvent at 0 --> 64 degrees C
      led to the desired 2-pyridinones in good yields and with excellent
      enantioselectivity. Use of these conditions allowed preparation of 2-pyridinones
      from several different Delta(2)-thiazolines and Meldrum's acid derivatives and
      may be a general route to 2-pyridinones.

PMID- 11578232
TI  - Formaldehyde oxime <--> nitrosomethane tautomerism.
AB  - Formaldehyde oxime <--> nitrosomethane tautomerism, isomeric nitrone, and their
      common cations and anions are studied with Gaussian-2 theory using MP2(full)/6
      31G geometries and with density functional theory using B3LYP/6-311+G**.
      Geometrical parameters, harmonic vibrational frequencies, relative stabilities,
      conformational stabilities, and ionization energies are compared with
      experimental gas-phase data when available. The formaldehyde oxime <-->
      nitrosomethane tautomerism is compared with the amide <--> imidol, imine <-->
      enamine, keto <--> enol, and nitro <--> aci-nitro tautomeric processes. Solvent
      effects are estimated by the self-consistent isodensity polarizable continuum
      model (SCIPCM). The influence of hydrogen bonding interactions with the solvent
      is addressed by including two water molecules. In the final evaluation,
      formaldehyde oxime is 15.8 kcal/mol more stable than nitrosomethane when the
      aqueous solvation correction of 3.8 kcal/mol is applied to the G2 energies.
      Unsolvated formaldehyde oxime is estimated to be 11.1 kcal/mol more stable than
      nitrone. The estimated gas-phase ionization energies (G2) are 362.5 kcal/mol for
      formaldehyde oxime, 350.6 kcal/mol for nitrosomethane, and 351.4 kcal/mol for
      nitrone.

PMID- 11578233
TI  - A chemoenzymatic total synthesis of ent-bengamide E.
AB  - The cis-1,2-dihydrocatechol 3, which can be obtained in enantiomerically pure
      form by microbial dihydroxylation of bromobenzene, has been converted into the
      enantiomer, ent-1, of the cyclolysine-based marine natural product bengamide E
      (1).

PMID- 11578234
TI  - Synthesis of a muscarinic receptor antagonist via a diastereoselective Michael
      reaction, selective deoxyfluorination and aromatic metal-halogen exchange
      reaction.
AB  - An efficient synthesis of a structurally unique, novel M(3) antagonist 1 is
      described. Compound 1 is conveniently disconnected retrosynthetically at the
      amide bond to reveal the acid portion 2 and the amine fragment 3. The synthesis
      of key intermediate 2 is highlighted by a ZnCl(2)-MAEP complex 19 catalyzed
      diastereoselective Michael reaction of dioxolane 7 with 2-cyclopenten-1-one (5)
      to establish the contiguous quaternary-tertiary chiral centers and a subsequent
      geminal difluorination of ketone 17 using Deoxofluor in the presence of catalytic
      BF(3).OEt(2). The synthesis of the amine moiety 3 is highlighted by the discovery
      of a novel n-Bu(3)MgLi magnesium-halogen exchange reaction for selective
      functionalization of 2,6-dibromopyridine. This new and practical metalation
      protocol obviated cryogenic conditions and upon quenching with DMF gave 6-bromo-2
      formylpyridine (26) in excellent yield. Further transformations afforded the
      amine fragment 3 via reductive amination with 35, Pd-catalyzed aromatic
      amination, and deprotection. Finally, the highly convergent synthesis of 1 was
      accomplished by coupling of the two fragments. This synthesis has been used to
      prepare multi-kilogram quantities of the bulk drug.

PMID- 11578235
TI  - Regioselective synthesis of polysubstituted pyrazoles and isoxazoles.
AB  - A regioselective synthesis has been developed for the preparation of
      unsymmetrical 1,3,5-triaryl-4-alkylpyrazolines and -pyrazoles by treatment of
      alpha-benzotriazolyl-alpha,beta-unsaturated ketones with monosubstituted
      hydrazines followed by alkylation at the 4-position of the pyrazoline ring.
      Reaction of alpha-benzotriazolyl-alpha,beta-unsaturated ketones with
      hydroxylamine gives 3,5-disubstituted isoxazoles regioselectively.

PMID- 11578236
TI  - Novel syntheses of 2,3-dihydro-1,5-benzothiazepin-4(5h)-ones and 2h-1,4
      benzothiazin-3(4h)-ones.
AB  - Nucleophilic additions of alpha-mercaptoalkanoate esters and beta
      mercaptoalkanoate acids to benzoquinone diimines, followed by cyclization with
      trifluoroacetic acid or 1,3-dicyclohexylcarbodiimide (DCC), provide novel, high
      yielding syntheses of 2H-1,4-benzothiazin-3(4H)-ones (3a-f) and 2,3-dihydro-1,5
      benzothiazepin-4(5H)-ones (5a-c), respectively.

PMID- 11578237
TI  - Synthesis of substituted 4(6)-amino-1,3,5-triazin-2-ones and -1,3,5-triazin-2
      thiones.

PMID- 11578238
TI  - Photochemical synthesis of cyclophanes containing tethered benzofuran rings.

PMID- 11578239
TI  - Efficient synthesis of optically pure (4R,6S)-4-(tert-butyldimethylsilyloxy)- 6
      (hydroxymethyl)tetrahydropyran-2-one and its enantiomer.

PMID- 11578240
TI  - Direct evidence on nucleophilic reactivity of secondary anilines toward an
      aminium radical.

PMID- 11578241
TI  - Synthesis of a deoxysugar dinucleotide containing an exo-difluoromethylene moiety
      as a mechanistic probe for studying enzymes involved in unusual sugar
      biosynthesis.

PMID- 11578242
TI  - Pressure dependent highly enantioselective hydrogenation of unsaturated beta
      amino acid precursors.

PMID- 11578243
TI  - Stereoselective synthesis of MeBmt and methyl (4R,5S)-5-isopropyl-2-
      phenyloxazoline-4-carboxylate by a Pd-catalyzed equilibration.

PMID- 11578244
TI  - Solid-phase synthesis of isoxazole-based amino acids: a new scaffold for
      molecular diversity.

PMID- 11578245
TI  - Pyridone annulation by 4 + 2 coupling of dienolates with nitriles and nitrile
      equivalents. A solution to the acetonitrile problem.

PMID- 11578246
TI  - Asymmetric synthesis of (+)-deoxoprosopinine.

PMID- 11578247
TI  - Orthogonally protected, enantiopure syn-2-amino-1,3,4-butanetriol: a general
      building block for syn-amino alcohols.

PMID- 11578248
TI  - Use of chiral HPLC-MS for rapid evaluation of the yeast-mediated enantioselective
      bioreduction of a diaryl ketone.

PMID- 11578251
TI  - Vitamin C causes cancer! St. John's wort useless for depression!

PMID- 11578252
TI  - Helicobacter pylori eradication: are there alternatives to antibiotics?
AB  - It is now generally accepted that infection with Helicobacter pylori is an
      important cause of peptic ulcer disease and that eradication of this organism
      greatly reduces the recurrence rate of ulcers. H. pylori also can cause chronic
      gastritis and hypochlorhydria and is a risk factor for gastric cancer.
      Conventional eradication therapies, which consist of two antibiotics plus either
      a proton-pump inhibitor or a bismuth compound, are highly effective, but can
      cause significant side effects in some cases. Alternative methods of eradicating
      H. pylori are therefore being investigated. To date, the research in this area is
      still preliminary, and no treatment has emerged as a clear alternative to the
      conventional triple-therapy regimens.

PMID- 11578253
TI  - Conjugated linoleic acid: a review.
AB  - Conjugated linoleic acid (CLA) refers to a group of positional and geometric
      isomers of the omega-6 essential fatty acid linoleic acid (cis-9, cis-12,
      octadecadienoic acid). In humans evidence is currently ambiguous as to whether
      CLA supplementation has a significant effect on body composition. Despite
      favorable changes in lipid levels in animal models, a beneficial effect in humans
      has not yet been established. While some of the changes reported are consistent
      with an improved lipid profile, declines in HDL and increases in lipoprotein (a)
      have also been observed in some subjects. Available evidence suggests CLA
      supplementation has no impact on immune system performance in healthy subjects.

PMID- 11578254
TI  - The therapeutic potential of melatonin in migraines and other headache types.
AB  - A large number of individuals suffer from migraine headaches. Several theories
      attempt to explain migraine etiology. One such theory holds that since
      environmental stimuli are well known to trigger migraine headaches, the pineal
      gland may be involved in migraine etiology. Specifically, a pineal gland
      irregularity may be the physical origin of migraine headaches, with subsequent
      physiological changes being secondary. Research has found the pineal hormone
      melatonin is low in migraine patients. Additionally, several studies found
      administering melatonin to migraine sufferers relieved pain and decreased
      headache recurrence in some cases. It has been suggested melatonin may play an
      important therapeutic role in the treatment of migraines and other types of
      headaches, particularly those related to delayed sleep phase syndrome. Current
      research supports the hypothesis that migraines are a response to a pineal
      circadian irregularity in which the administration of melatonin normalizes this
      circadian cycle; i.e., melatonin may play a role in resynchronizing biological
      rhythms to lifestyle and subsequently relieve migraines and other forms of
      headaches. In addition, research testing the administration of melatonin found it
      safe in migraine sufferers, with few or no side effects. However, a larger,
      randomized control trial is needed to definitively determine if administration of
      melatonin to migraine patients is effective.

PMID- 11578255
TI  - Metabolic and immunologic consequences of ABH secretor and Lewis subtype status.
AB  - Determining ABH secretor phenotype and/or Lewis (Le) blood group status can be
      useful to the metabolically-oriented clinician. For example, differences in ABH
      secretor status drastically alter the carbohydrates present in body fluids and
      secretions; this can have profound influence on microbial attachment and
      persistence. Lewis typing is one genetic marker which might help identify
      subpopulations of individuals genetically prone to insulin resistance,
      autoimmunity, and heart disease. Understanding the clinical significance of ABH
      secretor status and the Lewis blood groups can provide insight into seemingly
      unrelated aspects of physiology, including variations in intestinal alkaline
      phosphatase activity, propensities toward blood clotting, reliability of some
      tumor markers, the composition of breast milk, and several generalized aspects of
      the immune function. Since the relevance of ABH blood group antigens as tumor
      markers and parasitic/bacterial/viral receptors and their association with
      immunologically important proteins is now well established, the prime biologic
      role for ABH blood group antigens may well be independent and unrelated to the
      erythrocyte.

PMID- 11578256
TI  - L-glutamine.

PMID- 11578257
TI  - Echinacea.

PMID- 11578258
TI  - Use of the silicone T-tube to treat tracheal stenosis or tracheal injury.
AB  - BACKGROUND: Tracheal stenosis or tracheal injury is a troublesome disease.
      Traditional temporary tracheostomy and reconstruction can resolve some problems.
      However other problems such as subglottic stenosis and supracarinal stenosis,
      cannot be resolved by simple tracheostomy. The silicone tracheal T-tube presents
      a substitute for stent of this complicated disease. METHODS: Eleven patients with
      tracheal stenosis or tracheal injury were managed with the silicone T-tube
      prosthesis from 1995 to 1999. Among them 5 cases were characterized by subglottic
      and cervical stenosis, 4 cases supracarinal stenosis, and 2 cases tracheal
      injury. The silicone T-tube was used for about one year in all patients with
      satisfactory results. RESULTS: One patient was excluded from the study because of
      death due to unrelated disease. The T-tubes were removed successfully one year
      later. Among them, two patients with granuloma over the subglottic area were
      treated by CO(2) laser 2 to 4 times. The stoma was closed by repeated silver
      nitrate application. CONCLUSIONS: The silicone T-tube is a useful prosthesis for
      tracheal stenosis or tracheal injury with minimal complication in place of
      traditional tracheostomy or complex tracheal reconstruction.

PMID- 11578259
TI  - Relations of the c-myc gene and chromosome 8 in non-small cell lung cancer:
      analysis by fluorescence in situ hybridization.
AB  - BACKGROUND: Amplification of the c-myc gene has been reported in non-small cell
      lung cancer (NSCLC). We investigated the c-myc gene amplification and the
      numerical aberration of chromosome 8 by dual color fluorescence in situ
      hybridization (FISH) to evaluate the relation between possible genetic
      abnormalities, pathological factors and prognosis. METHODS: Tumor tissue samples
      were obtained from 31 patients with NSCLC who underwent lobectomy with
      mediastinal lymph node dissection. Samples were analyzed by FISH using 8 alpha
      satellite DNA probe and c-myc gene cosmid probe. The relation between genetic
      abnormalities, pathological factors (T factor, tumor size, and N factor), and
      prognostic factors was evaluated by univariate and multivariate analysis, and by
      the Kaplan-Meier method and log-rank analysis. RESULTS: Chromosome 8 aberrations
      were T1 (n=3), 44.0%; T2 (n=18), 35.7%; T3 (n=7), 40.0%; T4 (n=3), 39.7% (p=NS).
      The c-myc gene amplifications were T1, 54.3%; T2, 51.1%; T3, 51.0%; T4, 66.3%
      (p=NS). There was no difference between patients whose tumor was more than 5 cm
      (n=16), and 5 cm or less (n=15) in the rate of chromosome 8 aberration (39.3%:
      36.3%), or the rate of the c-myc gene amplification (52.1%: 53.7%). N factors for
      chromosome 8 aberrations were N0 (n=18), 35.9%; and N2 (n=11), 44.9% (p=NS). In
      the c-myc gene amplification, there was a significant difference between N0 and
      N2 (48.6%, 61.3%, p=0.040). In univariate and multivariate analysis, chromosome 8
      aberrations correlated with a poor prognosis (p=0.037 and p=0.041). The 5-year
      survival rate was 15.4% in patients whose rate of chromosome 8 aberrations was
      40% or more (n=13), which was significantly less than that in patients with an
      aberration rate of less than 40% (n=19, 57.9%, p=0.014). CONCLUSION: The c-myc
      gene amplification correlates with lymph node metastasis. Although there was no
      significant link between the amplification of the c-myc gene and clinical
      outcome, the numerical chromosome 8 aberrations was considered to be a factor for
      survival.

PMID- 11578260
TI  - Survival of non-small cell lung cancer patients with postoperative recurrence at
      distant organs.
AB  - BACKGROUND: Recurrence after complete resection of non-small cell lung cancer
      (NSCLC) is often observed. However, its influence on the prognosis of patients
      with recurrence is still unclear. PATIENTS AND METHODS: Of 468 consecutive
      patients with NSCLC undergoing complete resection during 10 years, 118
      experienced recurrence at distant organs. In such patients, the influence of the
      following variables on post-recurrent survival was analyzed; sex, age at
      recurrence, disease-free interval, cell type, pathological (p-) stage at
      operation, adjuvant therapy (thoracic radiation and/or chemotherapy), site of
      recurrence, and treatment against recurrence. To identify independent factors,
      multivariate analysis was performed for variables which were considered to be
      influential in univariate analysis. RESULTS: Mean post-recurrent survival time
      was 418 days, and survival rate at 2-years was 15.7%. Multivariate analysis
      revealed that female, early p-stage, younger age at recurrence, metastasectomy
      and intra-pulmonary metastasis were the significant favorable factors in patients
      with distant metastases. Adjuvant therapy and bone metastasis were marginally
      significant unfavorable factors. Chemotherapy for recurrence tended to prolong
      survival. Length of disease-free survival and post-recurrent survival exhibited a
      positive relationship with p-stage. Seven out of 16 patients who underwent
      metastasectomy survived more than 1000 days after recurrence. CONCLUSIONS:
      Patients even with recurrence in distant organs could expect for long survival if
      they are in the early p-stage of primary cancer or a resectable recurrent
      disease.

PMID- 11578261
TI  - Single atriocaval cannulation is associated with increased incidence of
      hypercirculatory failure after cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) can lead to hypercirculatory cardiac failure (HCF).
      Despite the activation of inflammatory mediators, the infusion of cardioplegic
      solution into the systemic circulation may result in decreased systemic vascular
      resistance and thus may cause HCF. The present prospective study was conducted to
      investigate in cardiac surgical patients the effects of single atrial versus bi
      caval venous drainage and intraoperative hemofiltration on the incidence of HCF.
      METHODS AND RESULTS: 120 patients undergoing coronary artery bypass surgery
      (CABG) were randomized in 3 groups: A- single atrial cannulation; B- single
      atrial cannulation and intraoperative zero fluid balance hemofiltration; C- bi
      caval cannulation. Myocardial protection was performed using cold crystalloid
      cardioplegia (Bretschneider's HTK) administrated into the aortic root and
      moderate hypothermia (32 degree C). Hemodynamics, fluid balance, vasoactive
      drugs, body temperature, and hemoglobin/hematocrit ratio were recorded during and
      up to 12 hours after surgery. We noted a significantly increased incidence of HCF
      in-group A (32%, n=13) and B (40%, n=16) when compared to group C (10%, n=4,
      p<0.05), with significantly increased requirements for vasoactive medication in
      patients developing HCF. CONCLUSION: The present study results demonstrate that
      single atrial cannulation is associated with a significantly higher incidence of
      HCF. This is presumably caused by infusion of cardioplegic solution into the
      systemic circulation.

PMID- 11578262
TI  - Evaluation of St. Jude Medical valve's long-term function by Doppler
      echocardiography.
AB  - In this study, the long-term function of St. Jude Medical valve (SJM valve) is
      evaluated by Doppler echocardiography. The subjects were 191 patients who
      underwent mitral or aortic valve replacement using SJM valve in our institute
      since July 1978 and had no clinical problem showing more than 50% of left
      ventricular ejection fraction. The patients were classified into 3 groups
      according to measurement period (within 5 years, 10 years and 15 years and more),
      and further classified by size and their results were compared. In every group by
      size, there was no significant difference among groups by measurement period. In
      the mitral valve position, peak pressure gradient and pressure half-time were not
      significantly different among groups by size. On the other hand, in the aortic
      valve position, pressure gradient in 21-mm group was significantly high among 21
      mm, 25-mm, and 27-mm groups, showing a negative correlation with size. As the
      result, it was suggested that SJM valve kept a good function more than 15 years
      after operation. From these results, it was considered that the patients with
      small annlus of the aortic valve needed annulus-enlarging procedure or use of
      Hemodynamic Plus series valves to keep the size of more than 23 mm.

PMID- 11578263
TI  - Early and long-term results of cardiovascular surgery in octogenarians.
AB  - The purpose of this study was to evaluate characteristics and outcomes of
      octogenarians undergoing cardiovascular surgery with cardiopulmonary bypass in a
      Japanese population. Thirty-one consecutive patients over 80 years of age
      underwent coronary artery bypass grafting 19 (61%), combined coronary artery
      bypass grafting and ventricular septal perforation closure 1 (3%), valve
      replacement 3 (10%), and prosthetic graft replacement 8 (26%). The early
      mortality rate was 16.1%. Survival estimates were 74% after 1 year, 74% after 3
      year, and 64% after 5 years. Emergency and urgent cases involved 16 (51.6%), and
      2 patients (6.5%), respectively. Multivariate analyses revealed that predictors
      of early mortality was preoperative left ventricular ejection fraction.
      Predictors of hospital death (within 3 months after surgery) were preoperative
      renal dysfunction, intraaortic balloon pumping, and age. Predictors of late
      mortality were chronic lung disease and age. Twenty-one patients expected to have
      died before surgery were living at home, and 9 (40.9%) patients were completely
      autonomous. Multivariate analyses revealed diabetes mellitus and a small number
      of bypass grafts were predictive risk factors for postoperative autonomy. Thus,
      cardiovascular surgery can be performed in octogenarians under 85 years of age
      with a favorable long-term outcome, when appropriately applied in selective
      octogenarians without significant comorbidity. If patients are over 85 years of
      age or have significant comorbidity, clinical treatment recommendations should be
      individually tailored while evaluating the risk of having or not having surgery
      and their life expectancy. QOL of survivors was almost satisfactory and
      significantly improved compared with a preoperative state.

PMID- 11578264
TI  - Hemorrhagic shock due to intrathoracic rupture of an osteosarcoma of the rib.
AB  - A 13-year-old girl presented with dyspnea and chest pain. Chest radiography
      showed a massive left pleural effusion. Computed tomography revealed a tumor of
      the fourth rib. A large bloody effusion was drained. Her anemia worsened
      (hemoglobin: 4.8 g/dl), and hemorrhagic shock ensued. An emergency thoracotomy
      was performed. Bleeding from the ruptured tumor was identified. The fourth rib,
      the tumor, and the adjacent tissues were resected. Histopathologic examination
      revealed a ruptured primary osteosarcoma of the rib with pleural dissemination.

PMID- 11578265
TI  - A surgical intervention using percutaneous cardiopulmonary support for
      contralateral pneumothorax following pneumonectomy.
AB  - We here, describe a 63-year-old man presenting with a contralateral pneumothorax
      following pneumonectomy. After setting up a percutaneous cardiopulmonary support
      (PCPS) system in advance in preparation for hypoxemia during the operation,
      resection of bullae was performed. His oxygen saturation and hemodynamic status
      were stable intraoperatively and we achieved a successful and safe operation
      swiftly. He had no complications and was discharged on the 10th postoperative
      day.

PMID- 11578266
TI  - One-stage operation for descending thoracic aortic aneurysm and left lung cancer:
      a case report.
AB  - We performed concomitant graft replacement for descending thoracic aortic
      aneurysm and pulmonary resection for squamous cell carcinoma of the left upper
      lobe in a 79-year-old man. The tumor reached the parietal pleura. No distance
      metastasis was found, and the tumor was diagnosed preoperatively as a stage IIB
      (N0, M0, T3) tumor. The descending thoracic aortic aneurysm was saccular, with
      greatest diameter being 55 mm, and extending from TH5 to TH8. A left upper
      lobectomy was performed, and after irrigation with a large volume of saline
      diluted with povidone iodine, graft replacement for the aortic aneurysm was
      performed under femoro-femoral partial bypass. To prevent postoperative graft
      infection, the greater omentum was dissected and placed over the resected
      pulmonary hilum and the graft. The patient's postoperative course was uneventful.
      There was no sign of infection, and the patient was discharged 1 month after
      surgery. Artificial graft wrapping with the greater omentum was useful for the
      prevention of the postoperative graft infection in this case of surgical
      treatment of lung cancer and descending thoracic aortic aneurysm.

PMID- 11578267
TI  - Cardiac reoperation in a patient with osteogenesis imperfecta: a case report.
AB  - A case of a 40-year-old man with dehiscence of the prosthetic aortic valve and
      recurrence of mycotic aneurysm of the left ventricular outflow tract with
      osteogenesis imperfecta is presented. He had an operation of aortic valve
      replacement and direct closure of the mycotic aneurysm for infective endocarditis
      twenty-one months ago. We performed reoperation of prosthetic aortic valve, patch
      closure of the mycotic aneurysm and graft replacement of the ascending aorta. He
      was complicated with multiple fractures of bilateral scapla and dislocation of
      left shoulder one postoperative day. Fortunately, cardiac reoperation was
      performed successfully in this patient despite anticipated difficulties with
      tissue friability with osteogenesis imperfecta.

PMID- 11578268
TI  - Strut fracture of Bjork-Shiley convexo-concave valve in Japan--risk of small
      valve size--.
AB  - BACKGROUND: The Bjork-Shiley convexo-concave (BSCC) prosthetic valve was
      introduced in 1979. Between 1979 and 1986, approximately 86,000 BSCC valves were
      implanted. By December 31, 1994, 564 complete strut fractures had been reported
      to the manufacture. We experienced a case of an outlet strut fracture and
      investigated the risk of BSCC prosthetic valve fractures in Japan. METHODS AND
      RESULTS: To investigate the risk factor of a strut fracture in Japan, we
      investigated published cases of strut fractures. Between 1979 and 1986, 2021 BSCC
      valves were implanted in Japan. By January 31, 2000, 11 complete strut fractures
      of 60-degree BSCC valves including our case had occurred. The patients were eight
      males and three females. The average age at valve replacement was 42.4+/-8.1
      years, and nine of eleven (81.8%) were patients < 50 years-old. The average age
      of the patients when the BSCC valve fractured was 47.7+/-6.4 years, and eight of
      eleven (72.7%) were patients <= 50 years old. All patients were implanted in the
      mitral position. The sizes of the BSCC valve were 27 mm (n=5) (45.5%), 29 mm
      (n=3) (27.2%), and 31 mm (n=3) (27.2%). Four patients died and seven patients
      survived. CONCLUSIONS: Although only 11 BSCC valve struts fractured and
      statistical analysis could not be performed, our findings suggest that the high
      risk group for a strut fracture in Japan is young male patients with a mitral
      valve, >= 27 mm in size with BSCC models manufactured before March 1982. When
      following-up patients with BSCC models manufactured before March 1982, the
      possibility of a strut fracture in all BSCC valve sizes should be kept in mind.

PMID- 11578269
TI  - Investigation of coronary artery bypass grafting for a patient with
      myelodysplastic syndrome.
AB  - A 79-year-old male with unstable angina, who had myelodysplastic syndrome (MDS),
      was treated with coronary artery bypass grafting (CABG). MDS causes refractory
      anemia accompanied by various degrees of granulocytopenia and thrombocytopenia.
      Pancytopenia caused by MDS may complicate patients with major infections and
      bleeding during cardiac surgery. There were very few patients with MDS who had
      undergone open-heart surgery. Three case studies, including this study, had
      reported successful cases of CABG in patients with MDS and the analogous diseases
      of MDS. We used granulocyte colony-stimulating factor (G-CSF), red blood cells
      (RBCs) and platelets transfusions in peri-operative state. We did not need a
      large amount of transfusion of RBCs and platelets in intra-operative and
      postoperative states. We had prevented major bleeding and severe wound infections
      in the acute postoperative state.

PMID- 11578270
TI  - Two cases of off-pump coronary artery bypass grafting combined with abdominal
      aortic aneurysm repair.
AB  - Two cases of coronary artery disease coexisting with abdominal aortic aneurysm
      were treated with off-pump coronary artery bypass grafting combined with repair
      of the aneurysm. The first patient was a 67-year-old man exhibiting a large
      pulsating abdominal mass. Abdominal computed tomography demonstrated a 9-cm
      aneurysm and coronary angiogram revealed a 90% stenosis of the obtuse marginal
      branch for which percutaneous transluminal angioplasty could not be performed. He
      underwent simultaneous single coronary artery bypass grafting without
      cardiopulmonary bypass, and bifurcated graft replacement. The second patient was
      a 71-year-old man who had acute myocardial infarction, and one month later
      underwent coronary angiogram which revealed three vessel disease in the coronary
      artery. Computed tomography revealed a 4-cm aneurysm, and angiography showed a
      90% stenosis of the left renal artery. He underwent a single stage operation that
      involved three coronary artery bypass grafting without cardiopulmonary bypass,
      straight graft replacement, and reconstruction of the left renal artery using the
      saphenous vein graft. The postoperative course was uneventful in both cases. We
      currently recommend a single stage operation involving off-pump coronary artery
      bypass grafting.

PMID- 11578271
TI  - Erectile dysfunction.

PMID- 11578272
TI  - Pathophysiology and diagnosis of male erectile dysfunction.

PMID- 11578274
TI  - The pharmacology and clinical pharmacokinetics of apomorphine SL.

PMID- 11578273
TI  - Current treatments and emerging therapeutic approaches in male erectile
      dysfunction.

PMID- 11578275
TI  - Mode of action of a new oral treatment for erectile dysfunction: apomorphine SL.

PMID- 11578276
TI  - Efficacy of apomorphine SL in erectile dysfunction.

PMID- 11578277
TI  - Safety and tolerability of apomorphine SL in patients with erectile dysfunction.

PMID- 11578278
TI  - The role of apomorphine SL in the treatment of male erectile dysfunction.

PMID- 11578279
TI  - Endovascular treatment of abdominal aortic aneurysm: a failed experiment.

PMID- 11578280
TI  - Ethics of consent to surgical treatment.

PMID- 11578281
TI  - Systematic review of randomized clinical trials of surgical treatment for carpal
      tunnel syndrome.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is a common disorder for which several
      surgical treatment options are available. However, there is no consensus on the
      most effective method of treatment. The object of this systematic review is to
      compare the efficacy of the various surgical techniques in relieving the symptoms
      of CTS and promoting return to work and/or activities of daily living. METHODS:
      Computer-aided searches of Medline, EMBASE and the Cochrane Controlled Trials
      Register were conducted, together with reference checking. A rating system, based
      on the number of studies and their methodological quality and findings, was used
      to determine the strength of the available evidence for the efficacy of the
      treatment. RESULTS: Fourteen studies were included in the review. None of the
      alternatives to standard open carpal tunnel release (OCTR) seems to offer better
      relief of symptoms. There is conflicting evidence about whether endoscopic carpal
      tunnel release results in earlier return to work and/or activities of daily
      living. CONCLUSION: Standard OCTR is still the preferred method of treatment for
      CTS. It is just as effective as the alternatives, but is technically less
      demanding, so incurs a lower risk of complications and of added costs.

PMID- 11578282
TI  - Effect of laparoscopy on immune function.
AB  - BACKGROUND: Laparoscopic surgery is believed to lessen surgical trauma and so
      cause less disturbance of immune function. This may contribute to the rapid
      recovery noted after many laparoscopic operations. Preservation of both systemic
      and intraperitoneal immunity is particularly important in surgery for sepsis or
      cancer and so an understanding of the impact of laparoscopy on immune function is
      relevant. METHODS: Literature on immunological changes following laparoscopy and
      open surgery was identified from Medline, along with cross-referencing from the
      reference lists of major articles on the subject. RESULTS AND DISCUSSION: Despite
      a few contradictory reports, systemic immunity appears to be better preserved
      after laparoscopic surgery than after open surgery. However, the local
      intraperitoneal immune system behaves in a particular way when exposed to carbon
      dioxide pneumoperitoneum; suppression of intraperitoneal cell-mediated immunity
      has been demonstrated in a number of studies. This feature may be clinically
      important and should be acknowledged when considering laparoscopic surgery in
      patients with malignancy or sepsis.

PMID- 11578283
TI  - Detection and clinical significance of occult tumour cells in colorectal cancer.
AB  - BACKGROUND: A variety of techniques have been employed for the detection of
      occult tumour cells in the blood, bone marrow and lymph nodes of patients with
      colorectal cancer. This review examines the methods used, results obtained and
      the clinical significance of studies in this field. METHODS: A Medline literature
      search was performed using the terms colorectal cancer, minimal residual disease,
      micrometastasis, polymerase chain reaction, reverse transcriptase polymerase
      chain reaction and immunocytochemistry; further references were obtained from key
      articles. RESULTS: Immunocytochemical examination of bone marrow is the benchmark
      for detecting clinically significant occult disease. Larger standardized studies
      are required to confirm the prognostic significance of molecular assays for the
      detection of tumour cells in blood and bone marrow. The prognostic significance
      of lymph node tumour cells detected by either immunohistochemical or molecular
      methods awaits further affirmation. CONCLUSION: Standardization of terminology
      and techniques used, combined with large prospective clinical studies, is
      required if detection of occult residual disease is to become a prognostic marker
      for recurrence in colorectal cancer.

PMID- 11578284
TI  - Randomized clinical trial comparing suture and mesh repair of umbilical hernia in
      adults.
AB  - BACKGROUND: Prosthetic repair has become the standard method for inguinal hernia
      and has excellent results. The question remains of whether the mesh technique
      could also improve results for umbilical defects. METHODS: The study was a
      randomized clinical trial comparing herniorrhaphy (primary suture) with
      hernioplasty (polypropylene mesh or plug) in 200 adult patients with a primary
      umbilical hernia. Patients at high anaesthetic risk (American Society of
      Anesthesiologists (ASA) grade IV) or those who needed emergency surgery were
      excluded. The mean postoperative follow-up was 64 months. The population studied
      included 118 women and 82 men with a mean age at presentation of 57 years. Some
      173 patients were ASA grade I-II and 27 were ASA III. The anaesthetic technique
      of choice was local anaesthetic infiltration plus sedation (98 per cent).
      RESULTS: There were no significant anaesthetic complications or surgical deaths.
      The mean duration of surgery was greater for mesh than for suture repair (45
      versus 38 min). Rates of early complications such as seroma, haematoma or wound
      infection were similar in the two groups. The hernia recurrence rate was higher
      after suture repair (11 per cent) than after mesh repair (1 per cent) (P =
      0.0015). CONCLUSION: Prosthetic repair could become the standard treatment for
      primary umbilical hernia in adults.

PMID- 11578285
TI  - Extent of ductal carcinoma in situ within and surrounding invasive primary breast
      carcinoma.
AB  - BACKGROUND: The aim of this study was to evaluate the pathological and
      morphological features of ductal carcinoma in situ (DCIS) within and surrounding
      invasive ductal carcinoma, and to investigate its relationship with clinical
      outcome and established prognostic variables. METHODS: One hundred and seven
      patients with primary operable invasive breast carcinoma and associated DCIS
      treated by simple or subcutaneous mastectomy or wide local excision with
      radiotherapy were assessed. Those with pure DCIS and insufficient tumour
      available for examination were excluded. The most representative haematoxylin and
      eosin-stained sections from the remaining 91 samples were selected and examined
      at x 100 magnification using a 45-point, 2-mm grid graticule. The entire section
      was assessed and the cell under each point of the graticule was classed as either
      normal (a), DCIS surrounded by normal tissue (b), invasive tumour (c) or DCIS
      surrounded by invasive malignancy (d). The volume ratio of DCIS in the normal
      (b/(a + b)) and invasive (d/(c + d)) tissue was then calculated. RESULTS: The
      DCIS volume within invasive tumour was not associated with outcome. The DCIS
      volume within adjacent normal tissue, however, was associated with local
      recurrence (P = 0.025), disease-free interval (P = 0.048), the occurrence of
      distant metastases (P = 0.019), death (P = 0.049) and disease-free survival (P =
      0.048). Volume ratios of DCIS in normal and invasive tissue were not related to
      known prognostic factors including lymph node stage, grade, tumour size, vascular
      invasion or patient age. CONCLUSION: There is a significant prognostic effect
      relating to the extent of DCIS associated with an invasive cancer, particularly
      with respect to local recurrence of tumour. This effect is restricted to the
      volume of DCIS in the tissue surrounding the invasive lesion rather than the
      intratumoral component.

PMID- 11578286
TI  - Rising incidence of post-transplant lymphoproliferative disease in kidney
      transplant recipients.
AB  - BACKGROUND: The purpose of this study was to determine whether the incidence of
      post-transplant lymphoproliferative disease (PTLD) has been increasing in renal
      transplant recipients in this centre. METHODS: Prospectively gathered data were
      analysed to establish trends in the epidemiology of PTLD in 1537 patients.
      RESULTS: Overall, PTLD occurred in 2.3 per cent of renal transplant recipients.
      An increase in its incidence coincided with the introduction of cyclosporin in
      the 1980s. However, there was a further increase in the incidence of PTLD in the
      1990s when the only change in immunosuppressive policy was the abandonment of
      pretransplantation blood transfusion. The latter increase was particularly
      pronounced in patients with early-onset PTLD in whom it presented within 600 days
      after transplantation. CONCLUSION: The incidence of PTLD has been increasing in
      renal transplant recipients. The recent increase appears to be independent of
      cyclosporin and may reflect the reduction in pretransplant blood transfusion.
      Changes in the incidence of PTLD may also mirror changes in the epidemiology of
      non-Hodgkin lymphoma in the general population.

PMID- 11578287
TI  - Pro- and anti-inflammatory cytokine release in open versus endovascular repair of
      abdominal aortic aneurysm.
AB  - BACKGROUND: Pro- and anti-inflammatory cytokine release occurs with abdominal
      aortic aneurysm (AAA) repair although the relative contribution of each is
      currently poorly understood. Ischaemia-reperfusion injury is thought to play a
      greater role following open (OR) than endovascular (ER) repair, with resultant
      greater perioperative morbidity. METHODS: Thirty-two patients undergoing OR (n =
      16) and ER (n = 16) of AAA were studied. Systemic venous (SV) blood was taken at
      induction (baseline), 0 h (last clamp off), 4, 24, 72 and 144 h, and femoral
      venous (FV) blood (indwelling catheter; lower torso venous effluent) at 0, 4 and
      24 h. The cytokines interleukin (IL) 6, IL-8 and IL-10 were measured in these
      samples. RESULTS: In OR, SV and FV IL-6 increased from baseline to a peak at 24 h
      (SV 589 pg/ml (P = 0.001 versus baseline) and FV 848 pg/ml (P = 0.05)) before
      declining at 144 h. In ER, there was a similar pattern but the increase was
      smaller (24 h: SV 260 pg/ml (P = 0.003 versus baseline) and FV 319 pg/ml (P =
      0.06)) at all equivalent timepoints compared with OR. IL-8 peaked earlier (4 h)
      from baseline in both groups before declining by 144 h, and significant
      differences between SV and FV were seen only in the OR group. IL-10 levels peaked
      in both groups at 24 h before declining at 144 h, and there were no significant
      locosystemic differences between the groups. CONCLUSION: Venous pro-inflammatory
      cytokine changes (IL-6) are consistent with significantly greater lower-torso
      reperfusion injury in patients undergoing OR. Smaller responses were seen after
      ER (IL-6 and IL-8), although both groups showed a similar anti-inflammatory
      response (IL-10); this pro- and anti-inflammatory imbalance may account for the
      increased morbidity associated with OR.

PMID- 11578288
TI  - Community mortality after ruptured abdominal aortic aneurysm is unrelated to the
      distance from the surgical centre.
AB  - BACKGROUND: Ruptured abdominal aortic aneurysm (RAAA) carries a high community
      mortality. Raigmore Hospital, Inverness serves Highland Region, an area the size
      of Wales with a population of 204,000. The aim of this retrospective review was
      to determine the community mortality and hospital mortality rates from RAAA in
      Highland Region and to assess whether distance travelled had any significant
      impact on survival. METHODS: Data were retrieved from hospital records, the
      Registrar General for Scotland and the Information and Statistics Division of the
      National Health Service in Scotland about patients diagnosed with RAAA between
      1992 and 1999. RESULTS: Of 198 patients with RAAA, 131 (66 per cent) were
      transferred to Raigmore Hospital while the other 67 (34 per cent) died in a
      community hospital or at home. Of those reaching Raigmore 109 (83 per cent) had
      surgery, of whom 65 (60 per cent) survived. The overall community mortality rate
      was 67 per cent while the hospital mortality rate was 50 per cent. The hospital
      and community mortality rates for patients living within 50 miles of Raigmore
      Hospital were 60 and 67 per cent respectively, compared with 26 and 68 per cent
      for those living more than 50 miles away. CONCLUSION: Distance from Raigmore
      Hospital had no significant impact on community mortality from RAAA.

PMID- 11578289
TI  - Value of POSSUM physiology scoring to assess outcome after intra-arterial
      thrombolysis for acute leg ischaemia (short note).

PMID- 11578290
TI  - Diagnosis and management of a mediastinal leak following radical oesophagectomy.
AB  - BACKGROUND: The aim of this study was to evaluate the diagnosis, management and
      outcome of mediastinal leaks following radical oesophagectomy with a stapled
      intrathoracic anastomosis. METHODS: Some 291 consecutive patients underwent two
      phase subtotal oesophagectomy with gastric interposition for malignancy. Patients
      with clinical suspicion of a leak were investigated with contrast radiology and
      flexible upper gastrointestinal endoscopy. RESULTS: Nineteen patients (6.5 per
      cent) developed a proven mediastinal leak at a median of 8 (range 3-30) days
      following surgery. Contrast radiology and flexible upper gastrointestinal
      endoscopy identified that 13 patients had an isolated leak from the
      oesophagogastric anastomosis and two had widespread leakage secondary to
      gastrotomy-line dehiscence. Endoscopy revealed a further four patients with
      gastric necrosis in whom contrast radiology was normal. In six patients the
      diagnosis of leakage followed an apparently normal routine contrast examination
      on day 5-8. All 13 isolated anastomotic leaks were managed non-operatively with
      targeted mediastinal drainage, intravenous antibiotics and antifungal therapy,
      nasogastric decompression and enteral nutrition; the mortality rate was 15 per
      cent (two of 13). Patients with gastrotomy dehiscence or gastric necrosis had a
      more severe clinical picture; they were managed with repeat thoracotomy and
      either revision of the conduit or resection and exclusion. Despite early
      intervention four of the six patients died. CONCLUSION: Routine postoperative
      contrast radiology cannot be recommended. On clinical suspicion of a leak
      patients require both contrast radiology and endoscopic evaluation. Isolated
      anastomotic leaks can be managed successfully with non-operative treatment,
      whereas more extensive leaks from the gastric conduit require revisional surgery
      which carries a high mortality rate.

PMID- 11578291
TI  - Non-operative management of the primary tumour in patients with incurable stage
      IV colorectal cancer.
AB  - BACKGROUND: Excision of primary colorectal cancer associated with irresectable
      synchronous metastases confers high morbidity and mortality with uncertain
      benefit. METHODS: For patients with incurable stage IV colorectal cancer,
      minimally symptomatic primary tumours were left in situ and 5-fluorouracil-based
      chemotherapy was administered systemically. Primary tumour-specific complications
      and survival were monitored. RESULTS: There were 13 men and 11 women with primary
      tumours in the right colon (eight), transverse colon (one), sigmoid colon (eight)
      or rectum (seven). Eleven patients had metastases limited to the liver (liver
      replacement less than 25 per cent in one, 25-50 per cent in four and more than 50
      per cent in six) and 13 patients had extrahepatic disease (lung or peritoneum).
      Four patients with sigmoid colon tumours developed bowel obstruction, which
      required an uncomplicated operation in two and deployment of colonic stents in
      two patients, at 1, 3, 12 and 20 months from diagnosis. Three further patients
      underwent right hemicolectomy for abdominal pain of uncertain aetiology, with
      poor symptomatic relief, and another had a potentially curative operation
      following disease downstaging. The overall median survival was 10.3 months with a
      1-year actuarial survival rate of 44 per cent. CONCLUSION: A policy to defer
      resection of minimally symptomatic primary colorectal cancer is associated with a
      low risk of complications before death from progressive systemic disease.

PMID- 11578292
TI  - Prevention of the neoplastic progression of Barrett's oesophagus by endoscopic
      argon beam plasma ablation.
AB  - BACKGROUND: Patients with Barrett's oesophagus have a risk of approximately 1 per
      100 patient-years for the development of oesophageal adenocarcinoma. Endoscopic
      ablation of Barrett's oesophagus has been shown to lead to the regrowth of a
      'neo' squamous epithelium if gastro-oesophageal reflux is controlled, but the
      incidence of subsequent tumour formation is unknown. METHODS: The follow-up of 55
      patients who underwent endoscopic ablation of Barrett's oesophagus by argon beam
      plasma coagulation (ABPC) is reported. Of the 55 patients, nine had low-grade
      dysplasia, nine had high-grade dysplasia and the remainder had non-dysplastic
      Barrett's metaplasia. Twelve patients had reflux control by antireflux surgery
      and the remainder received proton pump inhibitor therapy. Barrett's metaplasia
      was ablated by ABPC to within 2 cm of the gastro-oesophageal junction. RESULTS:
      To date, one patient has died and one patient was unable to complete treatment.
      The remaining patients were followed by regular endoscopic surveillance for a
      mean of 38.5 months to give a total follow-up of 173.5 patient-years. No
      malignancy has developed in any patient during follow-up. CONCLUSION: The absence
      of malignant complications in this study of prophylactic ablation of long-segment
      Barrett's oesophagus strengthens the argument for endoscopic ablation in the
      prevention of oesophageal adenocarcinoma.

PMID- 11578293
TI  - Randomized clinical trial of intravenous fluid replacement during bowel
      preparation for surgery.
AB  - BACKGROUND: Bowel preparation using purgatives has previously been shown
      significantly to increase haemoglobin concentration and decrease weight. This
      prospective randomized study assessed the effects of administering intravenous
      fluid during bowel preparation. METHODS: Patients having bowel preparation with
      Picolax for colonic procedures were randomized prospectively to receive no
      intravenous fluid (group 1) or calculated intravenous crystalloid based on body
      weight (group 2) during preparation. Physiological, haematological and
      biochemical variables were measured before and after bowel preparation. RESULTS:
      Forty-one patients were recruited with a median age of 69 (range 29-86) years, 22
      in group 1 and 19 in group 2. There was no difference between groups in any of
      the variables measured before bowel preparation. On completion, there was a
      significant difference between groups in mean weight loss (P = 0.01), postural
      change in systolic pressure (P = 0.015) and serum creatinine concentration (P =
      0.008). In addition there was a significant fall in erect blood pressure after
      bowel preparation in group 1 (P = 0.02). The mean urine output in group 1 was 982
      ml and in group 2 was 1808 ml (P = 0.004). The faeces weight between groups was
      not significantly different. CONCLUSION: Picolax bowel preparation has a
      significant dehydrating effect, which can be minimized by administering a
      simultaneous volume of intravenous fluid (mean 2 litres in this study).

PMID- 11578294
TI  - Effects of adenosine on ischaemia-reperfusion injury associated with rat pancreas
      transplantation.
AB  - BACKGROUND: During cold preservation, cellular consumption of adenosine
      triphosphate leads to the accumulation of nucleotides and nucleosides. The
      precise role of adenosine in modulating the inflammatory response of cold
      preserved pancreas after reperfusion remains to be elucidated. The aim of this
      study was to assess the influence of adenosine on the inflammatory response
      associated with the process of ischaemia-reperfusion in rat pancreas
      transplantation. METHODS: The effect of adenosine from preservation solution on
      the levels of high-energy nucleotides and their breakdown products after cold
      ischaemic preservation was determined. In addition, the inflammatory response
      associated with the process of ischaemia-reperfusion in pancreas transplantation
      was quantified with and without pretreatment with the adenosine antagonist
      theophylline, and during preservation of the organ in University of Wisconsin
      solution with and without adenosine. RESULTS: Adenosine from preservation
      solution is able to modify the nucleotide and nucleoside content of preserved
      pancreas, indicating that adenosine is incorporated and metabolized in tissue.
      Administration of the adenosine antagonist to transplanted rats moderated the
      increases in nitrite and nitrate, myeloperoxidase activity and lipoperoxidation
      levels in the pancreas. CONCLUSION: Adenosine in the preservation solution may
      enhance the inflammatory response in rat pancreas transplantation.

PMID- 11578295
TI  - Reintervention as a clinical trial endpoint after peripheral arterial bypass
      surgery.
AB  - BACKGROUND: Graft patency is usually the primary endpoint in studies of
      peripheral arterial bypass surgery, but gives only a limited indication of
      clinical outcome. The aim of this study was to evaluate reintervention as a study
      endpoint after femorodistal bypass surgery. METHODS: The database from a
      multicentre, prospectively planned study of 517 patients undergoing femorodistal
      bypass for severe ischaemia was used to investigate the predictive value of
      technical endpoints. Clinical symptoms, graft patency, vascular interventions and
      clinical outcomes were recorded for 12 months after operation. RESULTS: Complete
      follow-up data were obtained on 498 patients (96 per cent). Success in terms of
      patients' need for reintervention agreed with clinical outcome in 90 (95 per cent
      confidence interval (c.i.) 87-93) per cent of cases. Primary and secondary
      patency agreed with the clinical outcome in 80 (95 per cent c.i. 77-84) and 81
      (95 per cent c.i. 78-85) per cent of patients respectively. However, the best
      agreement with clinical outcome was obtained from the composite endpoint of
      'patient alive without reintervention': 92 (95 per cent c.i. 90-94) per cent.
      CONCLUSION: Recording the number of patients who did not need reintervention for
      12 months after femorodistal bypass gave a more accurate assessment of the number
      with clinical improvement than was obtained by recording bypass graft patency.
      Inclusion of patient survival in a composite endpoint increased the clinical
      relevance of this endpoint in patients with severe ischaemia who had femorodistal
      bypass surgery.

PMID- 11578296
TI  - Outcome of surgical treatment for carotid body paraganglioma.
AB  - BACKGROUND: The present study reviewed a 30-year experience of managing carotid
      body paraganglioma (CBP) and analysed clinical findings associated with
      perioperative morbidity. METHODS: Clinical records, radiological findings and
      pathological reports of all patients who presented with CBP between 1966 and 1997
      were reviewed. There were 39 consecutive patients with 45 tumours and median
      follow-up was 10 years. The Shamblin classification was used to define
      complication rates and long-term surgical results. RESULTS: Preoperative
      information derived from magnetic resonance angiography (MRA) and colour Doppler
      imaging (CDI) was comparable to that from standard four-vessel arteriography.
      Forty-one CBPs were resected in 35 patients. Six patients had bilateral tumours
      and seven had multicentric tumours. The median duration of operation and blood
      loss were substantially higher for Shamblin type III tumours. All major vascular
      complications (four of 39 patients) and permanent neurological complications
      (three of 39) were observed in type III tumours. CONCLUSION: Surgical planning
      and prediction of perioperative complications can be obtained by staging derived
      from MRA and CDI. Severe complications occur predominantly in type III CBPs.

PMID- 11578297
TI  - Small bowel obstruction after appendicectomy.
AB  - BACKGROUND: This study analysed the risk of surgically treated small bowel
      obstruction after open appendicectomy. METHODS: This was a historical cohort
      study of 245 400 patients who underwent open appendicectomy and population-based
      matched controls, identified by linkage of computer registries. Analyses were
      made with the life-table technique, Kaplan-Meier plots and Cox proportional
      hazards regression analysis. RESULTS: The cumulated risk of surgically treated
      small bowel obstruction after appendicectomy was 0.41 per cent after 4 weeks,
      0.63 per cent after 1 year and 1.30 per cent after 30 years of follow-up,
      compared with 0.003 per cent at 1 year and 0.21 per cent after 30 years of follow
      up among the non-operated controls. The highest risk was found after operation
      for other diagnoses (adjusted hazard ratio 5.2 (95 per cent confidence interval
      4.6-5.8)), followed by operation for perforated appendicitis (adjusted hazard
      ratio 3.5 (3.1-3.8)), non-specific abdominal pain (adjusted hazard ratio 2.6 (2.3
      3.0)) and mesenteric lymphadenitis (adjusted hazard ratio 2.4 (2.0-2.8)) compared
      with operation for non-perforated appendicitis. The relation with age was J
      shaped, with the lowest risk at 20-39 years. Women had a slightly lower risk than
      men. CONCLUSION: The risk of postoperative small bowel obstruction needing
      surgical treatment after open appendicectomy is lower than previously thought.
      Perforated appendicitis, negative appendicectomy and high age are the risk
      factors.

PMID- 11578298
TI  - Strategy for the surgical management of patients with idiopathic megarectum and
      megacolon.
AB  - BACKGROUND: Several surgical procedures have been used to treat idiopathic
      megabowel. A structured approach to the surgical management of megarectum/colon
      is reported. METHODS: Twenty-eight consecutive patients with megabowel referred
      for surgery were reviewed. All patients had conservative treatment for 6 months.
      Those failing to improve underwent full-thickness biopsy of the anorectal
      junction, anorectal physiology studies, colonic transit studies and evacuation
      proctography. Surgery involved excision of the abnormal large bowel and formation
      of an anastomosis (coloanal or ileoanal) using 'normal' bowel identified either
      by a defunctioning stoma or colonic motility studies. RESULTS: Eight patients
      responded to conservative management. Two patients were lost to follow-up and one
      died from unrelated causes. Two of the 17 patients who underwent full-thickness
      biopsy were cured by the procedure. Anorectal physiology, colonic transit and
      evacuation studies did not aid selection of the surgical procedure performed in
      15 patients: proctectomy and coloanal anastomosis (six), restorative
      proctocolectomy (three), panproctocolectomy (one) and defunctioning stoma (five).
      At a median follow-up of 3.6 years, 13 of 15 evaluable patients had a
      satisfactory outcome. CONCLUSION: Approximately 40 per cent of patients with
      megabowel referred for surgery responded to conservative treatment. The remaining
      patients may be treated successfully by surgery. The use of either a 'diagnostic'
      defunctioning stoma or colonic motility studies may aid in the choice of surgical
      procedure.

PMID- 11578299
TI  - Hospital caseload and the results achieved in patients with rectal cancer.
AB  - BACKGROUND: The aim of the study was to investigate the impact of hospital
      caseload on the short-term postoperative outcome of patients with rectal
      carcinoma. METHODS: A multicentre study involving 75 German hospitals was carried
      out between January and December 1999. Some 1463 patients with rectal carcinoma
      were studied. RESULTS: The hospitals were divided into three groups by annual
      caseload as follows: less than 20 (group 1), 20-40 (group 2) and more than 40
      (group 3). The groups were identical in terms of age, gender, height, weight,
      tumour stage, risk factors and American Society of Anesthesiologists
      classification. Postoperative morbidity was less in hospitals with a case volume
      of more than 20 patients per year (41.7 per cent in group 2 versus 49.9 per cent
      in group 1). The proportion of patients undergoing abdominoperineal resection
      with a permanent stoma was less in hospitals with a case volume of more than 40
      patients per year (26.4 per cent in group 3 versus 34.0 per cent in group 2).
      CONCLUSION: A large caseload in rectal surgery results in a significant reduction
      in permanent stoma formation and postoperative morbidity.

PMID- 11578300
TI  - Prospective controlled trial of a standardized meal stimulation test in the
      detection of pancreaticoduodenal endocrine tumours in patients with multiple
      endocrine neoplasia type 1.
AB  - BACKGROUND: Use of a standardized meal stimulation test has been recommended for
      the early diagnosis of pancreaticoduodenal endocrine tumours (PETs) in patients
      with multiple endocrine neoplasia type 1 (MEN 1). The diagnostic value of this
      test was re-evaluated. METHODS: In a prospective, controlled trial 58
      standardized meal stimulation tests (563 kcal) were performed in 12 patients with
      MEN 1 and histologically, biochemically and/or radiologically confirmed PETs
      (group 1), 11 carriers of an MEN 1 mutation with no evidence of PETs (group 2)
      and in 27 healthy controls (group 3). Serum pancreatic polypeptide (PP) and
      gastrin concentrations were measured before and during the test meal. RESULTS:
      Patients in group 1 had significantly higher mean basal serum PP and gastrin
      concentrations than patients in group 2 and controls (P < 0.05). In all three
      groups an increase in serum PP was observed after meal stimulation, but there was
      no significant difference between the groups. No increase in gastrin level was
      found in any of the groups after meal stimulation. CONCLUSION: The standardized
      meal stimulation test does not reliably indicate the presence of PETs in patients
      with MEN 1, whereas raised basal serum PP and gastrin levels do. The expensive
      and time-consuming meal test can be excluded from MEN 1 screening programmes.

PMID- 11578301
TI  - Influence of the number of lymph nodes examined on staging of gastric cancer.
AB  - BACKGROUND: Nodal staging for gastric cancer according to the 1997 Union
      Internacional Contra la Cancrum tumour node metastasis classification is based on
      the number of metastatic lymph nodes. The aim of this study was to evaluate
      whether the number of lymph nodes examined affected staging of gastric cancer.
      METHODS: A retrospective study was performed in 4789 consecutive patients with
      gastric cancer, who had undergone curative resection (R0) from 1986 to 1995.
      Patients were classified according to the number of nodes examined. The number of
      metastatic lymph nodes and stage-stratified survival were compared. RESULTS:
      There were significant differences in the number of metastatic lymph nodes and
      survival in stage IIIA between patients with 15 or more lymph nodes and those
      with fewer than 15 nodes. In analysis restricted to patients with 15 or more
      nodes, stage-stratified survival did not vary significantly with lymph node
      yields for any stage except IIIB, in which there was a significant difference
      between the subgroup with fewer than 20 examined lymph nodes and patients with 35
      or more nodes. CONCLUSION: The number of lymph nodes examined did not
      significantly affect node staging of gastric cancer as long as at least 15 nodes
      were examined. For stage IIIB, more than 15 lymph nodes may be required for
      optimal staging.

PMID- 11578302
TI  - Survey of the use of thromboprophylaxis in laparoscopic surgery in Denmark.
AB  - BACKGROUND: The aim of this study was to determine the current use of
      thromboprophylaxis for laparoscopic surgery in Denmark. METHODS: Postal
      questionnaires were sent to all Danish surgical departments that performed
      laparoscopic surgery according to the National Laparoscopic Cholecystectomy
      Database. RESULTS: There was a written protocol for thromboprophylaxis in 93 per
      cent of the responding departments. In 37 per cent thromboprophylaxis was used
      for all patients undergoing laparoscopic surgery; only 7 per cent used
      thromboprophylaxis sporadically. All departments used low molecular weight
      heparin, 74 per cent in combination with graduated compression stockings. The
      criteria for using thromboprophylaxis varied greatly; in many departments
      conversion of the procedure to an open operation was not considered a criterion.
      Some 20 per cent of the departments reported previous thromboembolic
      complications following laparoscopic surgery. CONCLUSION: Despite the widespread
      use of thromboprophylaxis, symptomatic thromboembolic complications were reported
      from several departments. Further studies are needed to determine whether
      laparoscopic surgery should be considered a high-risk procedure.

PMID- 11578303
TI  - A normal appendix found during diagnostic laparoscopy should not be removed (Br J
      Surg 2001; 88: 251-4).

PMID- 11578304
TI  - Re-excision of soft tissue sarcoma after inadequate initial operation (Br J Surg
      1995; 82: 278-9).

PMID- 11578305
TI  - An unexpected liver secondary (Br J Surg 2001; 88: 627-8).

PMID- 11578306
TI  - Procalcitonin strip test in the early detection of severe acute pancreatitis (Br
      J Surg 2001; 88: 222-7).

PMID- 11578307
TI  - Stapled haemorrhoidectomy: pain or gain (Br J Surg 2001; 88: 1-3).

PMID- 11578308
TI  - Role of resection and primary anastomosis of the left colon in the presence of
      peritonitis (Br J Surg 2000; 87: 1580-4).

PMID- 11578309
TI  - Linking genetic identity and function in communities of uncultured bacteria.

PMID- 11578310
TI  - Distribution of S-layers on the surface of Bacillus cereus strains: phylogenetic
      origin and ecological pressure.
AB  - Bacillus anthracis, Bacillus cereus and Bacillus thuringiensis have been
      described as members of the Bacillus cereus group but are, in fact, one species.
      B. anthracis is a mammal pathogen, B. thuringiensis an entomopathogen and B.
      cereus a ubiquitous soil bacterium and an occasional human pathogen. In two
      clinical isolates of B. cereus, in some B. thuringiensis strains and in B.
      anthracis, an S-layer has been described. We investigated how the S-layer is
      distributed in B. cereus, and whether phylogeny or ecology could explain its
      presence on the surface of some but not all strains. We first developed a simple
      biochemical assay to test for the presence of the S-layer. We then used the assay
      with 51 strains of known genetic relationship: 26 genetically diverse B. cereus
      and 25 non-B. anthracis of the B. anthracis cluster. When present, the genetic
      organization of the S-layer locus was analysed further. It was identical in B.
      cereus and B. anthracis. Nineteen strains harboured an S-layer, 16 of which
      belonged to the B. anthracis cluster. All 19 were B. cereus clinical isolates or
      B. thuringiensis, except for one soil and one dairy strain. These findings
      suggest a common phylogenetic origin for the S-layer at the surface of B. cereus
      strains and, presumably, ecological pressure on its maintenance.

PMID- 11578311
TI  - Localization of processes involved in methanogenic degradation of rice straw in
      anoxic paddy soil.
AB  - In anoxic paddy soil, rice straw is decomposed to CH(4) and CO(2) by a complex
      microbial community consisting of hydrolytic, fermenting, syntrophic and
      methanogenic microorganisms. Here, we investigated which of these microbial
      groups colonized the rice straw and which were localized in the soil. After
      incubation of rice straw in anoxic soil slurries for different periods, the straw
      pieces were removed from the soil, and both slurry and straw were studied
      separately. Although the potential activities of polysaccharolytic enzymes were
      higher in the soil slurry than in the straw incubations, the actual release of
      reducing sugars was higher in the straw incubations. The concentrations of
      fermentation products, mainly acetate and propionate, increased steadily in the
      straw incubations, whereas only a little CH(4) was formed. In the soil slurries,
      on the other hand, fermentation products were low, whereas CH(4) production was
      more pronounced. The production of CH(4) or of fermentation products in the
      separated straw and soil incubations accounted in sum for 54-82% of the CH(4)
      formed when straw was not removed from the soil. Syntrophic propionate
      degradation to acetate, CO(2) and H(2) was thermodynamically more favourable in
      the soil than in the straw fraction. These results show that hydrolysis and
      primary fermentation reactions were mainly localized on the straw pieces, whereas
      the syntrophic and methanogenic reactions were mainly localized in the soil. The
      percentage of bacterial relative to total microbial 16S rRNA content was higher
      on the straw than in the soil, whereas it was the opposite for the archaeal 16S
      rRNA content. It appears that rice straw is mainly colonized by hydrolytic and
      fermenting bacteria that release their fermentation products into the soil pore
      water where they are further degraded to CH(4). Hence, complete methanogenic
      degradation of straw in rice soil seems to involve compartmentalization.

PMID- 11578312
TI  - Measuring mass transfer processes of octane with the help of an alkSalkB::gfp
      tagged Escherichia coli.
AB  - Diffusion of octane from oily droplets in different microscale settings was
      measured using Escherichia coli expressing the stable green fluorescent protein
      (GFP) from the alkB promoter of Pseudomonas oleovorans. GFP fluorescence
      intensities were determined quantitatively at the single-cell level after 1.0 or
      2.5 h incubation and compared with different calibration series using known
      concentrations of octane. By immobilizing the E. coli sensor cells on the bottom
      glass plate of a microscope flow chamber, it was possible to monitor the
      diffusion process for octane in aqueous solution as a function of time and
      distance from non-aqueous phase droplets of octane alone or oily octane mixtures.
      When a gas phase was included in the flow chambers, octane transport could be
      demonstrated from the oily mixtures to the cells through both gas and liquid
      phase. Assays of non-immobilized sensor cells in microdroplets in the presence or
      absence of soil particles incubated with octane through the vapour phase revealed
      a slight reduction in the total amount of induced E. coli cells in the presence
      of soil. Our results indicate the power of using GFP-marked single-cell
      biosensors in determining microscale bioavailability of organic pollutants.

PMID- 11578313
TI  - 25S rDNA-based molecular monitoring of glomalean fungi in sewage sludge-treated
      field plots.
AB  - Recycling of sewage wastes in agriculture is likely to affect the biological
      activity of soils through contamination of ecosystems by pathogens and metallic
      or organic micropollutants. The impact of sewage sludge spreading under field
      conditions on arbuscular mycorrhiza (AM) formation by a community of glomalean
      fungi was evaluated using a nested polymerase chain reaction (PCR) and
      discriminating primers based on 25S rDNA polymorphisms to detect different fungal
      species within root systems. Medicago truncatula was grown in soil of field plots
      amended or not with a composted sewage sludge, spiked or not with organic or
      metallic micropollutants. Overall AM development in roots decreased with sewage
      sludge application, and the relative abundance of five AM fungal morphotypes in
      root fragments was modified by the input of composted sludges. Sewage sludge
      spiked or not with organic pollutants had a generally positive effect on the
      relative diversity of AM fungal populations in planta, whereas after spreading of
      the sludge spiked with metallic pollutants, no variation was observed in the
      abundance of different species.

PMID- 11578314
TI  - Molecular analysis of microbial community structure in an arsenite-oxidizing
      acidic thermal spring.
AB  - Electron microscopy (EM), denaturing gradient gel electrophoresis (DGGE) and 16S
      rDNA sequencing were used to examine the structure and diversity of microbial
      mats present in an acid-sulphate-chloride (pH 3.1) thermal (58-62 degrees C)
      spring in Norris Basin, Yellowstone National Park, WY, USA, exhibiting rapid
      rates of arsenite oxidation. Initial visual assessments, scanning EM and
      geochemical measurements revealed the presence of three distinct mat types.
      Analysis of 16S rDNA fragments with DGGE confirmed the presence of different
      bacterial and archaeal communities within these zones. Changes in the microbial
      community appeared to coincide with arsenite oxidation activity. Phylogenetic
      analysis of 1400 bp 16S rDNA sequences revealed that clone libraries prepared
      from both arsenic redox active and inactive bacterial communities were dominated
      by sequences phylogenetically related to Hydrogenobacter acidophilus and
      Desulphurella sp. The appearance of archaeal 16S rDNA sequences coincided with
      the start of arsenite oxidation, and sequences were obtained showing affiliation
      with both Crenarchaeota and Euryarchaeota. The majority of archaeal sequences
      were most similar to sequences obtained from marine hydrothermal vents and other
      acidic hot springs, although the level of similarity was typically just 90%.
      Arsenite oxidation in this system may result from the activities of these unknown
      archaeal taxa and/or the previously unreported arsenic redox activity of H.
      acidophilus- or Desulphurella-like organisms. If the latter, arsenite oxidation
      must be inhibited in the initial high-sulphide zone of the spring, where no
      change in the distribution of arsenite versus arsenate was observed.

PMID- 11578316
TI  - Mixed Mullerian tumors of the uterine corpus: a review.
AB  - The literature relating to mixed Mullerian tumors of the uterine corpus has been
      reviewed. A critical account of the clinico-pathologic features of these tumors,
      their prognosis and treatment is presented.

PMID- 11578317
TI  - The importance of the histologic processing of pelvic lymph nodes in the
      treatment of cervical cancer.
AB  - Four hundred and twenty surgical specimens from patients undergoing radical
      abdominal hysterectomy and complete pelvic lymphadenectomy for stage Ib, IIa or
      IIb cervical cancer underwent meticulous histologic and morphometric study.
      Complete processing of the extirpated lymphatic fatty tissue led to reproducible
      findings including the number of removed nodes, the number and size of tumor
      deposits in the nodes, and the location of the latter in the pelvis. An average
      of 32 nodes was removed per patient regardless of clinical size, tumor size, or
      stage. Thirty one per cent of patients with stage Ib disease had positive nodes
      as did 45% of those with stage IIb disease. The number of node metastases
      increased proportionally with the size of the primary tumor. In stage Ib 30% of
      the node metastases were smaller than 2 mm in diameter as were 21% of those in
      stage IIb. The size of the metastases was directly proportional to the size of
      the primary tumor. In patients with small tumors 43% of the nodes were smaller
      than 2 mm, as compared with 15% of those in patients with large tumors. The 5
      year survival rate of patients with negative nodes was 89.3%. Survival dropped to
      69.8% and 37.9% in patients with 1 or >/= 4 positive nodes, respectively. The 5
      year survival rate of patients with node metastases smaller than 2 mm and larger
      than 20 mm was 70% and 39%, respectively. In patients with identical numbers of
      positive nodes, survival decreased with increasing tumor size. In patients with
      tumors of a given size, the number of node metastases was an additional
      prognostic factor. The number of lymph nodes removed in a given patient is an
      objective measure of the thoroughness of a lymphadenectomy.

PMID- 11578318
TI  - Radical vulvectomy and bilateral inguinal-femoral lymphadenectomy through
      separate incisions-experience with 100 cases.
AB  - Over a 6-year period 100 patients with vulvar cancer were treated by radical
      vulvectomy and bilateral inguinal femoral lymphadenectomy performed through
      separate incisions. The average age of the patients was 68.8 years. Ninety
      patients had squamous carcinoma, six had melanoma and four had other vulvar
      malignancies. FIGO staging was stage 1-46, stage II-25, and stage III-23, and
      stage IVa-6. Twenty-seven patients were found to have spread of tumor to groin
      nodes, 21 unilateral and six bilateral. For patients with squamous carcinomas,
      groin nodes were positive in four of 45 (8.9%) with tumor diameter < 2 cm vs. 17
      of 42 (40.5%) with tumors> 2 cm. In 60 patients with unilateral squamous tumors,
      no isolated contralateral node metastases were found, however two of 13 patients
      (15.4%) with positive ipsilateral nodes had positive contralateral nodes also.
      One patient with negative nodes developed bilateral recurrent tumor in the skin
      bridges and subsequently died. Overall 5-year survival corrected for death from
      intercurrent illness was 74.6%. Corrected survival by stage for squamous
      carcinomas was as follows: stage I-96.7%, stage II-85%, stage III-45.8% and stage
      IV-50%.

PMID- 11578319
TI  - Testing the validity of a prognostic classification in patients with surgically
      optimal ovarian carcinoma: a 15-year review.
AB  - A retrospectively designed classification using stage, residuum and a variable
      which combines prognostic information from both grade and histology (histology
      grade variable) has been used at our institution to predict prognosis, and choose
      therapy in patients with ovarian carcinoma, stages I-III having no or small
      residuum. In this study, multivariate analysis of prognostic factors were
      performed over two time periods: Group 1 (1971-1978), contains the patients from
      which the original classification was derived, and Group 2 (1979-1985), contains
      a different cohort of patients who are used to test the validity and
      reproducibility of the original classification. Multivariate analysis showed that
      the prognostic significance of two variables changed over the two study periods:
      tumor grade, and residuum. It was found that in the ideal combination of grade
      and histologic type, when used in conjunction with stage and residuum in a
      prognostic classification, was unique to each patient cohort. Because of these
      changes, new and more accurate prognostic classifications were derived for Group
      2. However, when all classifications were examined, (including the original), the
      differences in their ability to stratify patients into risk categories was
      negligible, and there was no major advantage to using one classification over
      another for clinical applications. Thus, the retrospectively derived prognostic
      classification using grade, instead of a combined histology-grade variable, in
      conjunction with the other significant prognostic factors (stage and residuum),
      is preferred for prospective application, and for its simplicity.

PMID- 11578320
TI  - Interaction of interferon gamma and CPT-11, a new derivative of camptothecin, in
      human endometrial carcinoma cell lines.
AB  - The anti-proliferative effects of interferon gamma (IFN-gamma) and CPT-11, a new
      derivative of camptothecin, both singly and in combination, on two human
      endometrial carcinoma cell lines, HHUA and ISHIKAWA, were examined in vitro. The
      HHUA cells were responsive dose-dependently to IFN-gamma, while the ISHIKAWA
      cells were unresponsive to IFN-gamma. Both cell lines were responsive dose
      dependently to CPT-11. In both cell lines, IFN-gamma at clinically achievable
      concentrations (10 and 100 U ml-1 enhanced the anti-proliferative activity of CPT
      11 in the range of concentrations where CPT-11 showed more than 10% cell growth
      inhibition. Sequential treatment with CPT-11 followed by incubation with IFN
      gamma resulted in significant cell growth inhibition, but not vice versa. Flow
      cytometric studies indicated that the combined anti-proliferative effect did not
      correlate with cytokinetic alterations. Treatment with IFN-gamma did not change
      the extractable topoisomerase I activity of the HHUA and ISHIKAWA cells. The
      combination therapy of IFN-gamma and CPT-11 could provide a new approach against
      endometrial cancer.

PMID- 11578321
TI  - Efficacy and toxicity of very high-dose cisplatin in advanced ovarian carcinoma:
      4-year survival analysis and neurological follow-up.
AB  - Given the steep dose-response relationship with cisplatin, a pilot study on very
      high-dose cisplatin (HD-CDDP) was conducted in previously untreated patients with
      advanced ovarian carcinoma and postoperative residual tumor (RT). Thirty-seven
      patients (FIGO stages III-IV; RT> 0.5 cm) received three courses of HD-CDDP (a
      course of 40 mg m-2 day-1 for days 1-5, every 28 days). Twenty patients (54%)
      achieved clinical complete response (CR), 12 (32%) partial response (PR), and the
      remaining five (14%) showed stable or progressive disease (NC-P). All 20
      clinically complete responders underwent second-look laparotomy and CR was
      confirmed in all but five cases (pathologic CR: 40%) and in 71% of patients with>
      0.5-2 cm RT vs. 15% of those with> 2 cm RT (P < 0.001). The 4-year overall
      survival was 35% (median: 27 months, range: 7-58+), and 53% vs. 20% for patients
      with> 0.5-2 cm and> 2 cm RT, respectively (P = 0.01). The overall progression
      free survival was 29.5% (median: 16 months, range 2-58+) and for patients with
      more or less than 2 cm RT it was 20 and 41.2% (P < 0.05). Pathologically complete
      responders received no further treatment and showed a 3-year disease-free
      survival of 53%. The major toxic effect was a delayed-onset peripheral neuropathy
      observed in all patients, five of them (13.5%) with gait disturbances requiring
      continuous assistance. Nevertheless, none of them became wheelchair dependent and
      about 90% of the alive patients recovered at the 18-month neurologic follow-up,
      suggesting that cisplatin damage can be reversible. Ototoxicity was detected in
      all patients although only 19% of patients were symptomatic. HD-CDDP showed high
      activity in patients with> 0.5-2 cm RT, suggesting that the adverse significance
      of minimal RT may be partially overcome through an intensive chemical
      cytoreduction. Substantial neurotoxicity and the need for intensive care
      represent the major drawbacks. Further studies should delineate the exact role of
      HD-CDDP in optimally debulked patients, and a considerable effort should be made
      in rapidly achieving reliable data on the value of neuroprotectors in the
      prevention of the dose-limiting neurotoxicity.

PMID- 11578322
TI  - CA 125 measurements in ovarian cancer patients during their first postoperative
      week.
AB  - Cancer antigen 125 (CA 125) was measured in 17 patients with ovarian carcinoma
      before their primary operation and during the first week after surgery. The
      purpose was to correlate the change in the antigen level with the patient's
      survival. Before surgery normal (16-30 U ml-1 CA 125 values were measured in four
      patients and 13 had increased (75-11.356 U ml-1) antigen concentrations. After
      surgery the marker increased to 104-931% of the preoperative level in five
      patients. In 12 patients the post-operative antigen level decreased to 20-96% of
      the preoperative level. In seven of these patients CA 125 increased without
      exceeding the preoperative level, after the initial postoperative fall. Thus, the
      CA 125 level during the first week after primary operation of ovarian cancer
      patients seems to be influenced by other variable factors besides a reduced
      amount of tumor tissue. Therefore, an investigation of the correlation between
      the change in the CA 125 concentration within the first week after surgery and
      the survival of the patient cannot be performed for the time being.

PMID- 11578323
TI  - Advanced cervical carcinoma associated with pregnancy.
AB  - Sixty-two patients with frankly invasive (FIGO stages IB-IV) cervical carcinoma
      were diagnosed during pregnancy or within the first post-partum year. Thirty four
      (54.8%) had advanced disease (stages IIB-IV), a proportion higher than reported
      in comparable studies. This group was studied and compared with a control group
      of patients with advanced cervical cancer not associated with pregnancy.
      'Pregnant' patients were significantly younger but overall treatment modalities
      and survival were no different. Mode of delivery (vaginal vs. abdominal) did not
      influence the survival of study patients. Although not significant, there was a
      worse outcome for patients diagnosed antenatally (as opposed to post-partum).
      These results are pertinent to the management of advanced cervical carcinoma
      associated with pregnancy.

PMID- 11578324
TI  - Primary adenocarcinoma of the fallopian tube. Review of the literature.
AB  - An extensive review of the currently available literature on primary fallopian
      tube carcinoma is presented. The role of vaginal ultrasonography and the
      importance of an aggressive evaluation of every tubal deformity is stressed. A
      staging system which takes into account recent data on the biology of this
      malignancy is proposed. We emphasize the largely underestimated importance of
      early lymphatic spread of this disease, necessitating a thorough staging
      laparotomy with pelvic and para-aortic lymph node sampling in the apparent early
      stages. The need for adjuvant treatment is obvious, but until now no firm data
      exist as to what the optimal strategy should be. We recommend that until more
      representative studies are available, ovarian carcinoma protocols should be used
      in clinical practice.

PMID- 11578325
TI  - Reproducibility and prognostic value of histologic type and grade in early
      epithelial ovarian cancer.
AB  - From September 1981 to September 1986, 417 consecutive treated patients with
      epithelial ovarian cancer FIGO stage I and II were registered by the Danish
      Ovarian Cancer Group (DACOVA). Typing and grading were primarily performed by
      several pathologists, with and without training in gynecologic pathology. Review
      typing by one specially trained pathologist showed an agreement rate of 72% for
      serous and endometrioid carcinoma, 86% for mucinous and 100% for clear cell
      carcinoma. The agreement rate was calculated for patients primarily classified by
      pathologists trained in gynecologic pathology and for patients primarily
      classified by pathologists with and without training. The agreement rate was not
      better for the group of pathologists with special training in gynecologic
      pathology. Grading was performed according to two classifications: one based on
      architectural pattern and one on combined criteria. Review grading showed an
      agreement rate of 77% for architectural classification and an agreement rate of
      52% for combined classification. The agreement rate between the two grade
      classifications at review was only 62%. Combined grading showed a significant
      tendency towards classifying more tumors as low grade. All grade classifications
      had prognostic value. The poor agreement rate of both type and grade even when
      performed by pathologists with expertise in gynecologic pathology, calls for a
      better and more reproducible characterization of malignant ovarian tumors.

PMID- 11578326
TI  - Type I and Type II estrogen and progesterone binding sites in endometrial
      carcinomas: their value in predicting survival.
AB  - A simple and inexpensive immunocytochemical technique has been used to
      demonstrate estrogen (EB) and progesterone binding sites (PB) in endometrial
      carcinoma. Tumors were considered as being 'binding-site' rich if more than 40%
      of the component epithelial cells were positive for hormone binding sites (HB).
      By this criterion, over half of the adenocarcinomas studied were HB rich.
      Significantly higher 5- and 10-year survival rates were found in women whose
      tumors were HB rich compared with those whose neoplasms were HB poor, and a
      similar trend was established for patients with a combined EB rich/PB rich status
      versus that of EB poor/EB poor. This beneficial effect of a rich Type I and Type
      II receptor site status on survival, however, was shown only to a limited extent
      for EB. These results were independent of adjuvant treatment and of all clinical
      and histopathological features of known prognostic importance, save tumor
      differentiation. It is concluded that the immunocytochemical determination of HB
      status in formalin-fixed paraffin-embedded tissues adds significantly to the
      prognostic information available for endometrial adenocarcinoma.

PMID- 11578327
TI  - Accuracy of cervical smears in predicting the grades of cervical intraepithelial
      neoplasia.
AB  - This is a retrospective study carried out to assess the correlation between the
      cytology and histology of cervical intraepithelial neoplasia in 1325 women. A
      poor correlation between the cytologic and histologic diagnosis of the various
      grades of CIN was shown. Forty-one percent of smears with repeated borderline
      change and 50% of those predicting CIN1 showed a higher grade of CIN on
      histology. The overall apparent false negative rate of cervical smears for high
      grade CIN (CIN2 and CIN3) was 19% and for CIN3 alone was only 3%. It is therefore
      concluded that there is a consistent tendency for cervical cytology to
      underestimate the severity of histologic lesions and it is therefore important
      that the clinicians ensure adequate follow-up of patients whose smears show a
      lesser degree of abnormality.

PMID- 11578328
TI  - Infection after radical abdominal hysterectomy and pelvic lymphadenectomy:
      prevention of infection with a two-dose peri-operative antibiotic prophylaxis.
AB  - Surgical site-related infections occurred in 21% of 87 consecutive patients
      undergoing radical hysterectomy with pelvic lymphadenectomy (RHPL) without
      planned peri-operative prophylaxis. A prospective, randomized double-blind,
      placebo-controlled study was conducted in 68 consecutive RHPL patients. In the 32
      available patients with two-dose cefuroxime and metronidazole prophylaxis no
      surgical site-related infections developed as opposed to a rate of 14% in the 28
      patients in the placebo group (P < 0.05). In a prospective, randomized double
      blind study two two-dose antibiotic prophylactic regimens were compared in 105
      consecutive patients. Surgical site-related infections developed in one (2%)
      patient in the cefuroxime plus metronidazole group, and in six (12%) patients in
      the moxalactam group. This difference did not achieve statistical significance.
      The mean length of the postoperative hospital stay of the patients with scheduled
      surgical prophylaxis was significantly shorter (P < 0.01) than that of the
      patients operated on without surgical prophylaxis. A two-dose antibiotic regimen
      is recommended, because levels of antibiotics assayed in samples collected during
      the course of the operation indicated a rapid clearance of the antibiotics from
      the operative site, most likely due to the high volume of peri-operative blood
      loss.

PMID- 11578329
TI  - Evaluation of multiple biologic parameters in cervical carcinoma: high macrophage
      infiltration in HPV-associated tumors.
AB  - A number of diverse biologic parameters have been assessed prior to treatment in
      a series of patients with cervical carcinoma. Factors analyzed were HPV DNA
      presence, MHC class I expression, expression of the oncofetal antigen 5T4, the
      proportions of macrophages, lymphocytes and granulocytes in cell suspensions
      prepared from tumors, in vitro colony-forming efficiency (CFE) and a measure of
      intrinsic radiosensitivity, surviving fraction at 2 Gy. Several associations were
      found. First, HPV DNA-negative tumors contained a small, but significant,
      decreased number of tumor infiltrating macrophages compared with HPV DNA-positive
      tumors. Secondly, patients with HPV-positive tumors were significantly younger
      than those where no HPV was detected. Thirdly, loss of one or more specific
      alleles in MHC class I positive tumors resulted in higher numbers of tumor
      lymphocytes and CFEs. Finally, strong expression of the 5T4 antigen was related
      to a reduction in the proportion of macrophages in tumor cell suspensions. In
      addition, for stage I and II patients expression of the MHC class I molecule was
      associated with improved survival compared with patients with tumors where loss
      of expression was seen.

PMID- 11578330
TI  - Leiomyosarcoma (LMS) and endometrial stromal sarcoma (ESS) of the uterus. A
      survey of patients treated in the Norwegian Radium Hospital 1976-1985.
AB  - One hundred and twenty-seven patients with leiomyosarcoma (LSS) or endometrial
      stromal sarcoma (ESS) were treated at the Norwegian Radium Hospital during the 10
      year period 1976-1985. After a review of the histologic slides 14 of the original
      tumors were reclassified, three as carcinomas and in 11 cases no malignant
      criteria were found. Five-year survival was 67% and 39% for ESS and LSS,
      respectively. Malignancy grade was the most powerful prognostic criterion in
      patients who were considered radically treated with surgery. Patients with grade
      1 and 2 tumors had a prognosis similar to patients with endometrial carcinoma in
      contrast to the very gloomy outlook for patients with grade 3 and 4 (5-year
      survival 33%). For ESS the mitotic index also influenced the outcome. Despite
      widespread use of chemotherapy there is no clear indication that the prognosis
      for patients with the more aggressive types of sarcoma has improved in the period
      studied.

PMID- 11578331
TI  - Serum CA 125 as a tumor marker and the expression of c-erbB-2 oncogene in tubal
      malignancies.
AB  - Serum CA 125 levels were evaluated in 26 patients with fallopian tube
      malignancies. CA 125 was elevated preoperatively in seven samples (median 178 U
      ml-1 range 41-19021 U ml-1), and postoperatively in eight of nine (89%) samples
      collected from patients with residual disease (median 109 U ml-1 range 10-1883 U
      ml-1) but only in one of seven (14%) samples from patients without residual
      disease (median 14, range 5-170 U ml-1) (P < 0.001). Changes in the serum CA 125
      level during chemotherapy correlated with the clinical course of disease in 13 of
      14 patients with a pre-chemotherapy serum CA 125 level> 35 U ml-1. Nine patients
      with clinical remissions showed decreasing serum CA 125 levels, one with
      clinically stable disease showed decreasing levels and four with disease
      progression showed increasing levels. Serum CA 125 levels were measured in four
      patients before second-look laparotomy. Two of three with positive findings at
      laparotomy had elevated serum CA 125 levels whilst the third had a normal level.
      One patient with negative findings at second-look surgery had a normal CA 125
      level. Disease relapse was associated with elevated serum CA 125 levels in nine
      of 10 patients (median 108 U ml-1, range 27-38200 U ml-1). Using
      immunohistochemical staining, none of the tumors showed positive cytoplasmic
      staining for c-erbB-2 (NEU) oncogene. This report shows that CA 125 is a reliable
      tumor marker for monitoring patients with cancer of the fallopian tube during
      active treatment and follow-up.

PMID- 11578332
TI  - Immunohistochemical study of PCNA (proliferating cell nuclear antigen) in normal
      and abnormal endometrium.
AB  - To investigate the cell kinetics of human endometrial disorders immunolocation of
      PCNA (proliferating cell nuclear antigen) was performed in 69 specimens of
      normal, hyperplastic, or malignant endometrial tissue that had been fixed in
      formalin and embedded in paraffin. Immunoreactivity of PCNA was observed in all
      specimens examined. In the proliferative phase, PCNA positive cells were present
      in both the glands and stroma. In the secretory phase PCNA positive cells were
      seen principally in the stromal cells. A PCNA labeling index was obtained by
      counting one thousand cells per case. PCNA positivity in the proliferative phase
      was significantly higher than in the secretory phase (P < 0.01), but lower than
      in moderately differentiated (P < 0.01) or poorly differentiated (P < 0.05)
      adenocarcinoma. No significant differences in the PCNA labeling index were
      observed between hyperplasia and adenocarcinoma. These findings indicate that
      possible biologic differences between these proliferative endometrial lesions are
      probably not due to differences in cell proliferative activity, but rather to
      factors other than proliferation such as their ability to invade.

PMID- 11578333
TI  - The role of chemotherapy in squamous cell carcinoma of the uterine cervix: a
      review.
AB  - A critical review of the potential role of chemotherapy in the management of
      patients with squamous cell carcinoma of the uterine cervix is presented. Both
      its role in the management of recurrent and/or metastatic cervical cancer and its
      usefulness as part of the primary treatment of high-risk patients are discussed.
      It is emphasized that high-risk patients with cervical cancer should preferably
      be treated in specialized centers and entered into research protocols.

PMID- 11578334
TI  - Serum lipid-associated sialic acid levels in gynecologic malignancies.
AB  - Significantly elevated serum concentrations of lipid-associated sialic acid (LSA)
      were observed in 183 patients with invasive cervical carcinoma, 31 with uterine
      corpus adenocarcinoma and 71 with epithelial ovarian carcinoma prior to any
      treatment when compared with 50 normal control women (P < 0.05). Elevated LSA
      levels were also observed in five women with microinvasive cervical carcinoma and
      in four patients with uterine corpus leiomyosarcoma (P < 0.05). By contrast there
      were no significant elevations of serum LSA levels in 12 cases of cervical
      intraepithelial neoplasia, 32 of uterine corpus leiomyoma, 52 of benign ovarian
      cyst and 14 of mature ovarian teratoma when compared with normal control women.
      If the upper limit of the normal serum LSA concentration is set at 20 mg 100 ml
      1, uterine corpus malignancy was distinguished from benign uterine corpus tumor
      with a sensitivity of 71% and a specificity of 94%; and ovarian malignancies were
      distinguished from benign ovarian masses with a sensitivity of 82% and a
      specificity of 85%. The positive predictive values of LSA assays in uterine and
      ovarian masses were 93% and 85%, respectively, whilst the negative predictive
      values were 75% and 81%, respectively. The sensitivity of LSA assays in cervical
      carcinoma was 57%. The present study suggests that serum LSA assays may be useful
      for the detection of gyncological malignancies.

PMID- 11578335
TI  - Endometrial carcinoma in women aged 40 years or younger: a Japanese experience.
AB  - We report on the clinical and pathologic findings in 17 cases of endometrial
      carcinoma in Japanese women aged 40 years or younger. Age of the patients ranged
      from 16 to 40 years, with a median of 35 years. Nine of 17 tumors (52.9%) were
      stage I or II (FIGO 1988) but 8 (47.1%) were stage III. Four of the 8 patients
      with stage III disease had pelvic lymph node metastases and one also had para
      aortic lymph node metastasis. One patient had metastasis to the ovary and
      peritoneal cytology was positive in 4 patients. Histologically, 13 of these 17
      patients had endometrioid adenocarcinoma, 3 had adenoacanthoma and 1 had an
      undifferentiated carcinoma. Ten were well differentiated tumors (G1), 3 were
      moderately differentiated tumors (G2), and 4 were poorly differentiated tumors
      (G3). Nine of 17 (52.9%) showed deep myometrial invasion (more than a half of the
      myometrium) and 5 of 17 (29.4%) demonstrated lymphatic/vascular space invasion.
      Pelvic and para-aortic lymph node metastases were seen in 4 of 15 (26.7%) and 1
      of 15 (6.7%), respectively. Two of these 17 patients died of disease in a
      relatively short follow-up period. In our experience there is no difference in
      the survival rates between patients aged 40 years or younger and those over 40
      years.

PMID- 11578336
TI  - The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in the
      uterine cervix and cervical squamous neoplasia.
AB  - This is a retrospective study, in which PC10, a monoclonal antibody against
      proliferating cell nuclear antigen (PCNA) was used in the assessment of 20 cases
      of FIGO stage IB cervical carcinoma, 30 cases of CIN, 10 cases of koilocytosis
      and 20 cases in which the transformation zone was histologically normal. The
      results showed that in the normal transformation zone the proliferative
      compartment was confined to the first 1-2 suprabasal cell layers. In CIN the
      pattern of staining corresponded to the grade of the lesion. In viral wart
      lesions occasional koilocytes demonstrated strong nuclear staining. In all cases
      of stage IB cervical carcinoma the PC10 index was high, irrespective of tumor
      grade response to treatment.

PMID- 11578337
TI  - Expression of cytochrome P450 enzymes in the cervix. An immunohistochemical
      study.
AB  - The expression of cytochrome P450 isoenzymes (subfamilies) CYP1A, CYP2B, CYP2C,
      CYP3A and CYP4A in the histologically normal cervix was explored using a panel of
      polyclonal antibodies. There was variation in the intensity of
      immunohistochemical reaction between the isoenzymes and between the various
      components of the cervix. Half the subjects tested were smokers and had increased
      urinary cotinine levels. Statistical analysis revealed no significant differences
      between smokers and nonsmokers in the expression of these isoenzymes. The
      implications of these observations in relation to cervical carcinogenesis are
      discussed.

PMID- 11578338
TI  - A retrospective study into the occurrence of cervical glandular atypia in cone
      biopsy specimens from 1977-1978 with clinical follow-up.
AB  - Cervical glandular atypia (CGA) is now increasingly recognized in cone biopsy
      specimens removed for suspected cervical intra-epithelial neoplasia, although
      little is known of its natural history or pre-malignant potential. One hundred
      and eighty-three cone biopsy specimens received in our department during 1977 and
      1978 from the City and Women's hospitals, Nottingham were reviewed and assessed
      for the presence of squamous CIN and CGA. One hundred and sixty-seven cone
      biopsies contained CIN and 28 of these also contained CGA. Ten cone biopsies
      contained high-grade CGA, the remaining 17 containing low-grade CGA. One cone
      biopsy contained high-grade CGA only. Twenty-one of the 28 cases of CGA had been
      followed up by annual pelvic examination and cervical cytology. None of these
      cases have developed abnormal cervical cytology or invasive cervical carcinoma
      after 13 years follow-up, even though 13 cone biopsies contained CGA which
      appeared to be incompletely excised. We concluded that if CGA is pre-malignant,
      the latent period for its progression to invasive carcinoma is in excess of 13
      years. CGA of either grade is not, in itself, an indication for hysterectomy,
      allowing a conservative approach to management in the first instance.

PMID- 11578339
TI  - The influence of staging laparotomy for cervical cancer on patterns of recurrence
      and survival.
AB  - A matched paired study of surgically staged and non-surgically staged patients
      with stage II and III cervical carcinoma from October 1974 through August 1987
      was retrospectively performed. Eight of 55 (13.8%) had para-aortic lymph node
      involvement. After tailored extended field radiation 2/8 (25%) remain alive
      without evidence of disease. Patient survival although slightly in favor of the
      unstaged group was similar. Patterns of recurrence were similar amongst treatment
      groups. Para-aortic nodal recurrence, despite tailored radiation therapy, was
      identical (5.4%) in the staged and unstaged groups. Only one patient (not
      surgically staged) had an isolated para-aortic recurrence. With the morbidity of
      an operative procedure and similar survival rates and para-aortic nodal
      recurrence rates, the value of staging laparotomy in improved patient survival is
      questioned. Pelvic failure and other distant metastases continue to be the major
      sites of recurrences.

PMID- 11578340
TI  - Parameters of small bowel dysfunction in cervical cancer patients undergoing
      radiotherapy.
AB  - Small bowel dysfunction is an important problem in patients undergoing
      radiotherapy for cervical cancer and may take many forms. The spectrum of small
      bowel dysfunction includes subtle findings such as malabsorption and more obvious
      complications such as obstruction and fistula formation. Predicting who will
      experience small bowel dysfunction is important so that prospective studies of
      these compications can be planned. We undertook a controlled retrospective review
      of patients with stage IB cervical carcinoma looking for parameters of small
      bowel dysfunction and their predictors to help in the design of a prospective
      study. This analysis suggests that the interval to development is long. The best
      predictor of diarrhea requiring medication was the number of laparotomies. A
      large sample size of stage IB patients would be necessary to prospectively study
      small bowel dysfunction in this population.

PMID- 11578341
TI  - Laser conization for microinvasive carcinoma of the cervix. Short-term results.
AB  - Thirty-one patients with microinvasive carcinoma of the uterine cervix (less than
      3.0 mm invasion, no lymph vascular involvement), were treated with combination
      laser conization. The mean follow-up period was 36 months. No cases of invasive
      disease have been diagnosed during follow-up. Examination during follow-up
      revealed atypical columnar epithelium in one case, but the hysterectomy specimen
      was normal. Based on these short-term results, combination laser conization for
      microinvasive carcinoma of the cervix seemed a sufficient therapy. A precise and
      careful histopathologic evaluation, and the patient acceptance of a strict follow
      up schedule are mandatory to a decision to employ conservative management of
      microinvasive cervical carcinoma. Only long-term follow-up in patients treated by
      conservative therapy will be able to finally justify this approach.

PMID- 11578342
TI  - Mismanagement of choriocarcinoma due to a false low HCG measurement.
AB  - Accurate measurement of HCG is essential for the diagnosis and management of
      patients with choriocarcinoma. It is therefore important that clinicians are
      aware of the possible analytical problems associated with the HCG assay if delay
      in the diagnosis of this curable tumor is to be avoided. We describe the case of
      a 43-year-old woman with extensive lung metastases who had an unnecessary
      hysterectomy and lung biopsy and in whom the diagnosis of this potentially
      rapidly fatal tumor was delayed because of a falsely low HCG level measured by a
      commercial kit. This underestimation of HCG was due to the 'high dose hook'
      effect, which is described in detail, and methods for avoiding this analytical
      problem are described.

PMID- 11578343
TI  - Ovarian Sertoli-Leydig cell tumor: success with salvage therapy.
AB  - A case of metastatic ovarian Sertoli-Leydig cell tumor is presented. The patient
      achieved a complete pathologic response with four courses of cisplatin,
      vinblastine and bleomycin chemotherapy. Recurrence of the tumor was detected with
      elevated serum alpha-fetoprotein. After surgical debulking, the recurrence was
      treated with intra-arterial cisplatin and intravenous etoposide with pelvic
      radiation therapy followed by intravenous doxorubicin and cyclophosphamide. The
      patient is alive and disease free 75 months after initial diagnosis, 4 years
      after salvage therapy.

PMID- 11578344
TI  - Long-term results of concurrent radiation and chemotherapy for carcinoma of the
      cervix recurrent after surgery.
AB  - Between 1981 and 1991, 41 patients with carcinoma of the cervix recurrent only in
      the pelvis, or pelvis and para-aortic nodes after initial surgery, were treated
      with concurrent chemo-radiation (CT-RT). The total dose of radiation was tailored
      to the disease extent. Radiation was delivered to the pelvis and/or pelvis plus
      para-aortic nodes. Concurrent infusional 5-fluorouracil 1.5 g m-2 day-1 was
      delivered with bid radiation for one to three courses of 3 or 4 days. In
      addition, 10 patients received one or two courses of intravenous mitomycin C (Mit
      C) 6 mg m-2. Twenty-three of 40 evaluable (58%) had a complete response to CT-RT.
      Five have subsequently relapsed, two in pelvis alone, one in pelvis and distant
      sites and two with distant metastases only. Eighteen of 40 (45%) remain alive
      without disease from 3 to 113 months (median 57 months) after CT-RT. Sustained
      complete remissions and apparent cure have occured even in poor pronosis patients
      with pelvic side wall or common iliac nodal diease and those recurrent at short
      intervals from surgery. Using logistic regression the following varibles were
      examined for their prognostic significance for pelvic control and survival: Mit
      C, extent of pelvic diseases number of course of 5-FU, nodal status at original
      surgery and radiation dose. On multivariate analysis only the number of courses
      of 5-FU used was predictive of pelvic control and survival. Concurrent 5-FU and
      radiation is recommended as salvage therapy for patients wth recurrent
      locoregional cervical cancer.

PMID- 11578345
TI  - En bloc resection of epithelial ovarian tumors with concomitant rectosigmoid
      colectomy: the KEMH experience.
AB  - Between the years 1984 and 1988, 43 patients with bulky advanced stage epithelial
      ovarian carcinoma underwent en bloc pelvic resection with excision of the
      rectosigmoid colon as part of their primary cytoreductive surgery. Optimal
      cytoreduction was accomplished in over 70% of cases, and all women had complete
      debulking of their pelvic tumor. Primary anastomosis of the bowel was feasible in
      all cases and only two covering colostomies were performed. There were no
      postoperative leaks or fistulas. The postoperative morbidity was reflected by a
      mean postoperative hospital stay of 16 days. Our results suggest that this
      technique facilitates optimal cytoreduction of bulky pelvic tumor with an
      acceptably low morbidity in woman with advanced ovarian carcinoma.

PMID- 11578346
TI  - Characterization of high- and low-grade cervical intraepithelial neoplasia.
AB  - A need exists to characterize the various grades of cervical intrapithelial
      neoplasia (CIN), and attempt to differentiate between high- and low-grade
      lesions, that may have different behavioral and progressive potentials. The
      identification of patients with high- or low-grade CIN is useful, as it may allow
      identification of those patients that have true cancer precursors. Fifty patients
      referred for colposcopy with abnormal cytology were studied. Univariate analysis
      identified three factors as important predictors of histologic grade; the
      colposcopic opinion, lesion surface area and the index cytology (P < 0.005).
      Colposcopic opinion was associated with the index cytology (P < 0.01) and the
      lesion surface area (P < 0.005). Only the colposcopic opinion and the index
      cytologic smear appeared in the final model using a stepwise logistic regression
      analysis, indicating their independent prognostic importance in prediction of
      grade of abnormality in cervical intraepithelial neoplasia. The study
      demonstrates the value of colposcopic training and experience being necessary
      prior to utilizing excisional treatment methods if overtreatment is to be
      avoided.

PMID- 11578347
TI  - Urinary drainage following radical hysterectomy for cervical carcinoma - a pilot
      comparison of urethral and suprapubic routes.
AB  - Twenty-four patients who underwent radical hysterectomy and pelvic node
      dissection for cervical carcinoma were randomized in a pilot study to compare
      continuous postoperative drainage by urethral and suprapubic catheters. There
      were no statistically significant differences in either the duration of
      continuous catheter drainage before the return of spontaneous voiding or the
      incidence of urinary tract infection in the two groups. Power calculations reveal
      that 628 patients require to be entered into each arm of a future study in order
      to be able to detect the former difference should it exist (alpha = 0.05, beta =
      0.2, difference = 16% of one s.d.) and 41 in the latter (alpha = 0.05, beta =
      0.2, 92.9% urethral group had UTI, 70% suprapubic group had UTI). We conclude
      that differences in these objective measures of catheter efficacy and morbidity
      between the groups, if they exist, are clinically irrelevant. On this basis we
      suggest that individual gynaecological oncologists should continue to use
      whichever method of catheter drainage best suits their clinical practice.

PMID- 11578348
TI  - Prognostic factors and adjuvant treatment in early epithelial ovarian cancer.
AB  - Four hundred and ten patients with epithelial ovarian cancer FIGO stages I and II
      were registered by a Danish multicenter study group (The Danish Ovarian Cancer
      Group - DACOVA). Two-thirds were stage I, the most frequent substage was Iai
      which was the classification in 27%. Five-year survival for stage I was 72%, and
      38% for stage II. Multivariate analysis showed that age, stage, residual tumor,
      histologic grade and adjuvant treatment had prognostic value. For stage, three
      significantly different groups could be identified: (1) stage Iai, (2) stage Iaii
      Ic, and (3) stage II. Histologic grade showed a significant survival difference
      between all grades. Adjuvant treatment had a moderate but significant impact on
      survival. Patients in stage Iai had a good survival with surgery alone and will
      probably not benefit from adjuvant therapy. Adjuvant treatment improved survival
      for the remaining patients in stages I and II without residual tumor. A
      difference between treatment modalities was not observed. However, the data need
      to be confirmed by a randomized trial. Patients in stage II with residual tumor
      should be treated as stage III.

PMID- 11578349
TI  - Histopathologic prognostic factors in stage IIb cervical carcinoma treated with
      radical hysterectomy and pelvic-node dissection - an analysis with mathematical
      statistics.
AB  - Of 107 patients with stage IIb cervical cancer who underwent laparotomy, 82 (77%)
      could be treated with radical hysterectomy (RAH) and pelvic-node dissection
      (PND). The remaining 25 patients were unsuitable for radical surgery because of
      para-aortic lymph node metastases, direct cancer invasion into the bladder
      muscle, and/or fixed enlarged pelvic lymph nodes (PLN): Such patients were
      treated with radiation therapy after laparotomy. Fifty-nine of RAH patients were
      given postoperative pelvic radiation because they had PLN metastases, parametrial
      invasion, and/or full thickness cervical stromal invasion. The overall 5-year
      survival of the patients undergoing RAH was significantly better than that of
      those who could not be treated with RAH (P < 0.001). In the RAH patients,
      parametrial invasion, which clinically defines stage IIb, was found only in 45%.
      Univariate analysis of histopathologic prognostic factors revealed that PLN
      metastasis, parametrial invasion, adenocarcinoma, and lymph-vascular space
      invasion significantly affected survival of the RAH patients (P < 0.05).
      Multivariate analysis using Cox's proportional hazards regression model, however,
      selected only PLN metastasis as a strong prognostic factor (P < 0.001).
      Concerning PLN metastasis patients with two or more positive nodal groups vs.
      49%, P < 0.0001). The logistic regression analysis revealed that tumor diameter,
      parametrial invasion and lymph-vascular space invasion were independently
      correlated with PLN metastases in two or more nodal groups. The present data
      suggest that (i) the patients with massive pelvic extension of cancer cannot be
      cured by radiation therapy alone, (ii) the strong determinant of the prognosis of
      the patients undergoing RAH and PND is PLN metastasis. Therefore, for these
      patients with poor prognosic factors, other treatment modalities should be
      considered. From the present study it seems that planning RAH and PND for
      patients with stage IIb disease might make it possible to select poor prognostic
      subgroups, who have extra cervical extension or PLN metastases in two or more
      groups, and be useful in individualizing treatment.

PMID- 11578350
TI  - Can we predict a high risk group in stage I epithelial ovarian cancer?
AB  - A retrospective review of 373 patients with stage I invasive epithelial ovarian
      cancer was undertaken over a 5 year period to develop a model to characterize the
      patient at high risk. Actuarial 5-year survival was 70%. To identify factors with
      an independent effect on 5-year survival, a logistic regression analysis was
      performed. Adjuvant chemotherapy, histologic grade and peritoneal washings, were
      identified as independent variables. A model to determine the predictivity of
      survival was created using a learning sample (2/3 of the cases) and the model was
      then used to reclassify a validation sample (1/3 of the cases). Using all the
      independent variables, outcome was predicted correctly in 78% of cases. However
      the model failed to improve identification of those at risk of recurrence
      (specificity of 53%).

PMID- 11578351
TI  - Radical hysterectomy and pelvic lymphadenectomy for early invasive cancer of the
      cervix - 14-year experience.
AB  - During a 14-year period, 397 radical hysterectomies and pelvic lymphadenectomies
      were performed for early invasive carcinoma of the cervix. Twenty-one patients
      were in stage IA2 with lymphatic/vascular channel permeation (5.2%), 340 in stage
      IB (85.6%) and 34 in early stage 2A disease (8.5%). Eighteen patients (4.5%) were
      pregnant. Adenocarcinoma comprised 26.9% of cases. The mean operative time was
      4.14 h; the intraoperative blood loss was less than 1.51 in 77.3% patients. There
      was no operative mortality; one patient died 3 weeks after surgery from
      clostridium difficile enterocilitis. Eleven patients (2.7%) developed venous
      thrombosis; severe lymphedema occurred in four (1%). The incidence of uretero
      vaginal fistula was 0.2% and that of vesico-vaginal fistula 0.5%. Ovarian
      metastases were noted in 4.3% of cases with adenocarcinoma. Sixty-six patients
      had positive nodes (16.6%). Five-year survival in patients with more than 2
      positive nodes was 68%. The use of adjuvant chemotherapy in patients with 'high
      risk' factors resulted in survival rates approaching those without risk factors.
      Neo-adjuvant chemotherapy was used in 10 patients with large bulky tumors; the
      results were favorable. Recurrences occurred in 47 patients (11.8%); 36 patients
      have died (9.1%). Age did not appear to influence survival. The overall 5-year
      survival was 92.2%.

PMID- 11578352
TI  - 'Abnormal' Papanicolaou smears and colposcopy in pregnancy: ante- and post-partum
      findings.
AB  - Abnormal Papanicolaou smears and colposcopic findings suggesting human Papilloma
      virus (HPV) infection and cervical intraepithelial neoplasia (CIN) may occur
      during pregnancy. Condylomata acuminata often grow rapidly during pregnancy and
      may regress spontaneously following delivery. However, the post-partum outcome of
      the untreated ante-partum abnormal cytologic smear and colposcopy has not been
      defined clearly. Seventy-three pregnant patients were examined by colposcopy
      because of genital warts and/or abnormal Papanicolaou smears. Cytologic,
      colposcopic and histologic re-evaluation was conducted after delivery. Only one
      of the patients had a normal ante-partum colposcopic examination. This number
      increased to 15 after delivery. Forty-one patients had normal post-partum
      cytologic smears, but only 13 had normal histology. Abnormal post-partum cytology
      was highly predictive of abnormal colposcopy and histology. In contrast, normal
      post-partum cytology was not very accurate in predicting normal colposcopy and
      histology. It is concluded that a few pregnant patients may have partial
      regression of clinical HPV infection and abnormal cytology and colposcopy after
      delivery. However, the majority will continue to have abnormal findings 4 months
      following delivery in spite of normal post-partum cytology and even colposcopy.

PMID- 11578353
TI  - A matched study of surgically treated stage IB adenosquamous carcinoma and
      adenocarcinoma of the uterine cervix.
AB  - Thirty-eight patients with surgically treated stage IB adenosquamous carcinoma of
      the uterine cervix (AS) have been matched with patients with other histologic
      subtypes of adenocarcinoma (A) for stage, lesion size, node status, grade of
      adenocarcinoma and age at diagnosis. An additional six patients with AS were
      unable to be matched. Overall 5-year survival and disease-free survival for the
      matched AS and A were not significantly different, 83 vs. 90%, and 78 vs. 81% nor
      were the number of recurrences, 8/38 AS vs. 6/38 A, but the mean time to
      recurrence was significantly shorter in the AS group: 11 vs. 32 months (P =
      0.003). A subgroup of AS with a high risk of a poor outcome can be identified
      based on either lesion size >/= 4 cm, depth of invasion >/= 10 mm or plevic lymph
      node metastasis. These patients may be suitable candidates for adjuvant therapy
      before or after surgical treatment.

PMID- 11578354
TI  - Increased levels of a lower molecular weight form of secretory component in
      cervical scrapes from women with cervical intraepithelial neoplasia.
AB  - The protein composition of 'negative' and 'positive' cervical scrapes has been
      compared using electrophoresis to determine whether differences were present that
      could be used to pre-select specimens with negative cytology. Only one minor
      difference in the 75-80 kDa region of the silver-stained patterns was detected in
      extracts from two well-matched groups. Further studies using 2D-electrophoresis
      and Western blotting identified the major components in this region as two forms
      of secretory component (SC) and transferrin. Subsequent blotting of 13 extracts
      from patients with negative smears and 17 extracts from patients with positive
      smears indicated very significant differences in the expression of the two forms
      of SC (P < 0.0002), the 'negatives' having more of the higher Mr form and the
      'positives' having more of the lower Mr form. Measuring SC could prove useful for
      pre-screening cervical scrapes, but more investigations are required to establish
      the nature of the change and a quantitative method for its detection.

PMID- 11578355
TI  - Preoperative CA-125 levels predict poor prognostic pathologic features in early
      stage, FIGO grade 1 and 2 endometrial adenocarcinoma.
AB  - Preoperative CA-125 levels were studied in patients with favorable histology and
      early clinical stage endometrial adenocarcinoma to determine its ability to
      predict the presence of poor pathologic prognostic features on final pathology.
      One hundred and one patients with clinical stage I (N = 65) or II (N = 19) or
      diagnosed by endometrial curettage (EMC) only (N-17) with grade 1 or 2
      endometrial adenocarcinoma without gross cervical involvement underwent
      preoperative CA-125 levels. Final pathology was reviewed for five poor prognostic
      pathologic features: FIGO grade 3 histology, unfavorable histologic type
      (sarcoma, clear cell, or papillary serous), invasion into the outer third of the
      myometrium, extension to the cervix, and extra-uterine metastases. Fifteen
      patients (14.9%) had CA-125 levels greater than 30 IU ml-1. Of these 15 patients,
      12 had one or more of the five poor prognostic pathologic features (positive
      predictive value 80.0%, specificity 95.8%, P < 0.0001). However, since 30 of the
      101 patients were found to have one or more of these poor prognostic pathologic
      features the sensitivity was only 40.0%. When clinical stage I patients were
      analyzed separately three patients (4.6%) had CA-125 levels greater than 30 IU ml
      -1 (positive predictive value 100%, specificity of 100%, sensitivity of 21.4%, P
      = 0.008). For patients with clinical stage II carcinoma, CA-125 was not
      predictive of pathologic findings except as a negative predictor of disease in a
      subgroup of patients whose endocervical curettage (ECC) demonstrated carcinoma
      unattached to endocervical tissue. In patients diagnosed by EMC only, an elevated
      CA-125 level was associated with poor prognostic pathologic features (P = 0.001).
      An elevated preoperative CA-125 reliably predicts advanced disease even in
      patients with apparently favorable histology and clinical stage, however the
      sensitivity of this method remains low.

PMID- 11578356
TI  - Gestational trophoblastic tumors: cytostatic treatment response evaluated from
      hCG modelling.
AB  - Fifty-eight patients representing with gestational trophoblastic tumors were
      treated at the department of Gynaecologic Oncology of the Norwegian Radium
      Hospital during the period from 1977 to 1990. Individual serial measurements of
      hCG were analyzed applying a mathematical dynamic tumor marker model.

PMID- 11578357
TI  - Expression of HER-2/neu oncoprotein, DNA-ploidy and S-phase fraction in advanced
      ovarian cancer.
AB  - The immunohistochemical expression of HER-2/neu and cytofluorimetric data were
      retrospectively analyzed in a group of primary advanced ovarian cancers. Thirty
      three out of 94 (35%) cases showed a specific p185/neu immunoreaction. No
      correlation between p185/neu expression and any of the clinico-pathologic
      parameters examined was observed. As far as cytofluorimetric data are concerned,
      38 out of 69 (55%) of the tumors were diploid (DNA index = 1) while 31 (45%) were
      aneuploid (DNA index from 1.10 to 2.50 with a median value of 1.50). Ovarian
      tumors were defined as of low and high S-phase fraction in 68% and 32% of the
      cases, respectively. Tumor ploidy and S-phase fraction did not correlate with the
      clinico-pathologic characteristics or p185/neu oncoprotein expression. Aneuploid
      tumors had a higher S-phase fraction (mean: 15.81 +/- 13.44) than diploid tumors
      (mean: 8.89 +/- 7.98) (P < 0.01). p185/neu expression failed to affect
      significantly both overall and progression free survival. On the other hand tumor
      ploidy was found to be related to the prognosis of advanced ovarian cancer
      patients although the difference was not statistically significant. As far as
      progression free survival is concerned, the median time to recurrence was not
      reached for diploid cases whereas it was 21 months for aneuploid cases (P <
      0.05). The 5-year survival for patients with a low S-phase fraction (58%) was
      significantly higher than for patients with high S-phase fraction tumors (28%) (P
      < 0.01). Median time to recurrence was 48 and 17 months for low and high S-phase
      fraction tumor patients, respectively (P < 0.05). However, in a multivariate
      analysis both tumor ploidy and S-phase fraction did not retain their prognostic
      value. The assessment of the role of the parameters examined in improving the
      prognostic characterization of ovarian cancer patients should be investigated in
      large multicenter clinical trials.

PMID- 11578358
TI  - Prediction of malignancy using transvaginal color flow Doppler in patients with
      gynecologic tumors.
AB  - Eighty-five patients referred to the Women's Cancer Center, University of
      Minnesota had transvaginal color flow Doppler performed to determine if pelvic
      malignancy could be predicted by blood flow assessment. Their mean age was 49
      years (range 21-86 years). Thirty-five patients were subsequently found to have
      malignant tumors of the cervix, uterus or ovary. The presence of increased
      intratumoral blood flow as depicted by color flow Doppler had a sensitivity of
      83%, specificity of 100%, positive predictive value (PPV) of 100% and negative
      predictive value (NPV) of 89% for malignancy. The mean intratumoral Pulsatility
      Index (PI) of the patients with malignant tumors was 0.81 (SD 0.24; range 0.3
      1.2), which was significantly lower than for the benign group (P = 0.001). A PI
      of </= 1.0 had a sensitivity of 96.3%, specificity of 94.3%, PPV of 89.7% and NPV
      of 98% for predicting malignancy. Transvaginal color flow Doppler shows promise
      as a method of predicting malignancy in patients with gynecologic pathology.

PMID- 11578359
TI  - The prognostic value of serum CA 125 in patients with advanced ovarian carcinoma:
      an analysis of 573 patients by the Medical Research Council Working Party on
      Gynaecological Cancer.
AB  - A number of studies have suggested that serum CA 125 levels may be an important
      prognostic factor for survival of patients with ovarian carcinoma. We
      investigated, in a large group of patients from 11 UK centers, which combination
      of CA 125 measurements provided the best prognostic index, and whether the
      predictive power could be improved by the addition of other factors. Analysis of
      the data from 248 patients showed that the absolute value of the third CA 125
      sample was the single most important factor for predicting progression at 12
      months, with the addition of residual bulk only slightly improving the predictive
      power. Seventy-four patients had CA 125> 70, and of these 57% were correctly
      predicted to progress or die within 12 months, but 43% remained alive and
      progression free. The best predictor for progression produced a false positive
      rate of 19%. We therefore conclude that prognostic information based upon CA 125
      measurements up to the start of the third course of initial chemotherapy is not
      accurate enough to be used to manage individual patients.

PMID- 11578360
TI  - Investigation of loss of heterozygosity at specific loci on chromosomes 3p, 6q,
      11p, 17p and 17q in ovarian cancer.
AB  - In an attempt to further define the genetic events in the pathogenesis and
      progression of human ovarian cancer, an analysis of constitutional and ovarian
      carcinoma DNA samples revealed loss of heterozygosity (LOH) at specific loci on
      chromosomes 3p (38%), 6q (23%), 11p (33%), 17p (82%) and 17q (62%). In contrast,
      LOH was not observed in benign or borderline tumors. No significant association
      could be demonstrated between LOH at the loci studied and tumor stage, histologic
      subtype, grade or patient outcome. Further analyses of large tumor panels are now
      required to determine the relationship between LOH at these loci and the
      clinicopathological behavior of ovarian tumors.

PMID- 11578361
TI  - Evaluation of serum CA 125 level as a tumor marker in borderline tumors of the
      ovary.
AB  - Serum CA 125 was evaluated as a tumor marker in 85 patients with borderline
      ovarian tumors. Serum CA 125 levels were elevated preoperatively in 18 of 20
      (90%) samples (median 66, range 5-272 U ml-1). Preoperative serum CA 125 levels
      did not correlate to FIGO stage. Preoperative serum CA 125 levels were elevated
      in seven of nine (78%) with serous tumors (median 131, range 5-272 U ml-1) and in
      all 11 with mucinous tumors (median 62, range 41-157 U ml-1). There was no
      significant difference in the CA 125 levels between these two histologic types.
      Postoperative serum CA 125 levels, measured 3-6 weeks after primary laparotomy,
      were significantly lower than the preoperative ones (P < 0.001). No difference in
      the postoperative CA 125 levels was found between those with and those without
      residual disease after surgery. Postoperative serum CA 125 levels were elevated
      in eight of 60 (13%) without residual tumor. None of these had relapsed at the
      time of analysis (26-87 months after surgery). Serum CA 125 levels tended to
      correlate with disease evolution during chemotherapy. Two with disease remissions
      had falling levels, one with stable disease had falling level and one with
      disease progression had rising level. Serum CA 125 samples were obtained before
      second-look laparotomy in seven patients. Two with negative findings at second
      look had normal levels. Of five with positive findings at laparotomy only two had
      elevated serum CA 125 levels. Disease relapse was associated with elevated serum
      CA 125 levels in only one of six patients.

PMID- 11578362
TI  - Concurrent interstitial radiotherapy and infusional chemotherapy for recurrent
      gynecologic malignancies.
AB  - Patients with unresectable locally recurrent gynecologic malignancies pose a
      difficult therapeutic challenge. Conventional therapies are frequently
      unsuccessful and offer only marginal palliation. In this study, interstitial
      192iridium-needle implants and concomitant infusional 5-fluorouracil (5FU) and
      cisplatin (CDDP) or carboplatin (CBDCA) chemotherapy were used to treat 14 women
      with recurrent pelvic tumors. Malignancies of the cervix, endometrium ovary, tube
      and vulva are represented; all patients were heavily pretreated. Twenty
      interstitial implants were performed in these 14 patients. Needle distributions
      and doses were individualized to accommodate the recurrent tumor volumes. Tumor
      responses were seen in 12 patients (six complete and six partial responses). Four
      women remain clinically free of disease and four are alive with disease at 18-34
      months of follow-up. There were no severe acute toxicities, however, four
      patients have subsequently developed fistulae associated with tumor progression.
      Although longer follow-up is required, the high response rate, wide applicability
      and acceptable toxicity observed in this heavily pretreated patient population
      warrant further study of combined interstitial radiation and chemotherapy.

PMID- 11578363
TI  - Gonadotropin-releasing hormone stimulates phospholipase C but not protein
      phosphorylation/dephosphorylation in plasma membrane from human epithelial
      ovarian cancer.
AB  - In view of advances in treatment of certain hormone-dependent cancers with
      analogues of gonadotropin-releasing hormone (Gn-RH), this study was undertaken to
      establish the signal transduction events interacting with Gn-RH receptor in a
      cell-free system prepared from human ovarian mucinous cystadenocarcinoma samples.
      A high affinity specific binding (Kd=8 x 10-9 M) of [3H] Gn-RH was demonstrated
      in two from two plasma membrane preparations. Gn-RH showed no effects on the rate
      of protein phosphorylation from [gamma-32P] adenosine triphosphate in the plasma
      membrane preparations. On the other hand, incubation of plasma membrane isolated
      form [3H]inositol-labeled specimens with Gn-RH in the presence of guanosine
      thiotriphosphate resulted in the rapid production of inositol phosphates. The Gn
      RH effects was concentration-dependent, and half-maximal activation occurred with
      1-3 nm Gn-RH. The Gn-RH-stimulated membrane event was observed in all plasma
      membrane isolations tested, but not in those from uterine endometrial carcinoma
      of a given case. These results provide the first direct evidence that Gn-RH
      receptor is coupled to phosphoinositide hydrolysis but not to certain membrane
      protein phosphorylation/dephosphorylation in ovarian carcinoma plasma membrane.
      Though the functional role of this event in human ovarian cancer is still
      obscure, it might be part of a possible point of attack for therapeutic
      approaches using Gn-RH analogues in this malignancy.

PMID- 11578364
TI  - Use of local flaps in the preservation of fecal continence following resection of
      perianal neoplasias.
AB  - The feasibility of achieving curative resection of perianal pre-invasive and
      invasive lesions with preservation of fecal continence was studied prospectively.
      Resection of these lesions involved excision of as much as the anterior third of
      the external anal sphincter. Twenty-two patients had invasive cancer and nine had
      extensive carcinoma in situ suspicious for invasive disease on preoperative
      assessment. Anal reconstruction consisted of plication of the external anal
      sphincter and plication of the puborectalis muscles. The perianal/perineal
      defects were closed using bilateral rhomboid flaps in 21 patients, unilateral
      rhomboid flaps in five patients and local advancement flaps in five patients.
      Twenty-eight patients were ultimately continent of feces, although two required
      further surgery for incontinence. Two of the three incontinent patients had fecal
      incontinence before surgery. Two patients had recurrence of invasive cancer,
      neither of which was perineal or perianal. Curative surgery of selected perianal
      lesions with preservation of fecal continence can be achieved with local
      resection and reconstruction with the use of local full thickness skin flaps.

PMID- 11578365
TI  - Intraperitoneal interferon-alpha-2b for patients with no macroscopic disease
      following second-look laparotomy.
AB  - Low to intermediate doses of interferon-alpha-2b (10-30 million units every 2
      weeks for six cycles), were administered intraperitoneally to 14 patients with no
      macroscopic disease at the completion of second-look laparotomy. Eight patients
      had a negative second-look so the treatment was given as consolidation therapy.
      Five patients had a microscopically positive second-look and one patient had
      small macroscopic disease completely resected. Toxicity was low. However, four of
      the eight patients with a negative second-look relapsed (two in the peritoneum)
      and five of the other six patients have also relapsed, all in the peritoneum.
      Four of these latter six patients received intraperitoneal cisplatinum in
      addition to the interferon. Mean time to relapse for the group with a negative
      second-look was 18 months, while it was 16 months for the group with microscopic
      residual disease. Median follow-up was 38 months. Intraperitoneal interferon in
      the dosages given in this trial does not seem to be effective as consolidation
      therapy, nor is it effective for patients with microscopic residual disease at
      second-look laparotomy.

PMID- 11578366
TI  - Retrospective review of 41 patients with endodermal sinus tumor of the ovary.
AB  - Forty-one patients with endodermal sinus tumors of the ovary (EST) (23: pure EST,
      nine: EST with dysgerminoma; and nine: EST with immature teratoma) were treated
      with cytoreductive surgery, with or without subsequent adjuvant chemotherapy
      including VAC or PVB. Clinical staging of these patients showed 23 in stage I,
      six in stage II and 12 in stage III and IV. The outcome was good in the patients
      with stage I or II disease, with 5- and 10-year survival rates of around 80%. In
      contrast, all except two patients with stage III or IV disease died within 2
      years. Aggressive surgery did not change the outcome of patients with stage I
      disease. In addition, postoperative chemotherapy was necessary, but the choice of
      vincristine, actinomycin-D and cyclophosphamide (VAC) or cis-platin, vinblastine
      and bleomycin (PVB) did not make any difference. Based on the results of the
      present study, VAC or PVB chemotherapy, after cytoreductive surgery, is essential
      for cure and conservative surgery followed by VAC or PVB regimen should be
      recommended for young patients.

PMID- 11578367
TI  - Radiotherapeutic management in carcinoma of the uterine cervix: current status.
AB  - Despite refinement in the delivery of external radiation and brachytherapy, there
      has been little improvement in the survival rate of patients with invasive cancer
      of the uterine cervix in recent years. With advancing stage disease, there is an
      increase in both local failure and distant metastases. Although recent efforts to
      improve local control for late stage disease have been encouraging, research
      efforts should be directed to the identification of new active drugs for
      radiation sensitization and systemic therapy. Also, due to early detection,
      therapeutic investigations should focus on the high-risk subsets of patients with
      early stage disease.

PMID- 11578368
TI  - DNA ploidy; the most important prognostic factor in patients with borderline
      tumors of the ovary.
AB  - The prognostic significance of DNA ploidy in relation to clinical and
      histopathologic factors was evaluated in a retrospective study of 370 patients
      treated at the Norwegian Radium Hospital from 1970 to 1982 with complete follow
      up of median 149 months. Evaluable flow cytometric DNA histograms from paraffin
      embedded tissue from the primary tumor were obtained in 321 cases, 293 (91%) were
      diploid and 28 (9%) were aneuploid. Aneuploidy was associated with older age,
      more advanced disease and non-serous histologic types. By multivariate analysis
      the only parameters with prognostic significance for corrected survival (death
      from disease) were ploidy, stage, histologic type and age. The patients with
      aneuploid tumors had a 19-fold increased risk of dying of disease compared with
      patients with diploid tumors. In tumor-free operated patients the extent of
      surgery had no influence on survival, neither had postoperative treatment. Using
      the prognostic factors the patients could be divided into risk groups. The large
      group of patients with diploid stage I tumors belonged to the low risk group.
      Fertility-saving operations can be offered to patients with diploid stage IA
      tumors, all others should have bilateral salpingo-oophorectomy and omentectomy
      with or without hysterectomy. Patients with diploid stage I tumors should not
      receive adjuvant treatment. The value of adjuvant chemotherapy in the high risk
      group needs further investigation.

PMID- 11578369
TI  - Extraperitoneal metastases after intraperitoneal chemotherapy of ovarian cancer
      patients with a negative second-look laparotomy.
AB  - The site of the first detectable recurrence was recorded in 17 consecutive stage
      II-IV ovarian carcinoma patients who, after a negative second-look laparotomy,
      received intraperitoneal chemotherapy with cisplatin and thiosulfate kidney
      protection. Although the progression-free interval and survival were favorable,
      11 patients eventually had a recurrence and in six (54.5%) of these it was
      extraperitoneal. Brain metastases were detected in three patients. The appearance
      of extraperitoneal metastases is not always ominous.

PMID- 11578370
TI  - Immunohistochemical study of p53 expression in endometrial carcinomas:
      correlation with markers of proliferating cells and clinicopathologic features.
AB  - Using anti-p53 (PAb1801 and PAb240), anti-DNA polymerase alpha and Ki-67
      monoclonal antibodies, the expression of p53 was studied in 11 normal endometria,
      14 endometrial hyperplasias and 27 endometrial carcinomas and its relationship to
      the proliferative activity of the tumors was examined. Normal endometria and
      simple hyperplasias were completely negative for p53. The PAb1801 indices of
      complex hyperplasias and complex atypical hyperplasias were 2.5+/-1.8% and 5.0+/
      3.2%, respectively. The PAb1801 indices of grade 1, grade 2 and grade 3
      endometrial carcinomas were 10.2+/-14.2%, 44.4+/-29/0% and 45.0+/-32.5%,
      respectively. These results indicate a progressively enhanced p53 expression in
      the sequence from normal endometrium, through hyperplasia to carcinoma. A
      significant correlation between p53 expression and labeling indices of Ki-67 and
      DNA polymerase alpha was observed in endometrial carcinomas. The endo-metrial
      carcinomas with p53 overexpression developed mainly in post-menopausal patients
      and were frequently high-grade tumors with deep myometrial invasion. These
      findings may indicate that overexpression of p53 protein contributes to the
      proliferative activity of the tumor cells.

PMID- 11578371
TI  - Ultraradical surgery for advanced carcinoma of the vulva: an update.
AB  - From July 1, 1955 to March 31, 1989 24 patients with locally advanced vulvar
      cancer underwent ultraradical resection. Three patients had received prior
      radiotherapy. Seventeen of the 24 patients underwent posterior exenteration, four
      underwent anterior exenteration, and the remaining three required a total pelvic
      exenteration. One patient died 3 months postoperatively of fulminating infection
      considered to be a complication of the operation. Three other patients
      experienced serious complications, including postoperative hemorrhage, severe
      urinary sepsis, and colostomy stoma necrosis. Eleven (46%) of the 24 patients
      have remained alive without evidence of recurrent cancer for at least 3 years. Of
      the 10 patients known to have died of recurrent cancer, nine had positive lymph
      nodes at the time of surgery. It may be reasonable to utilize ultraradical
      surgery in patients with clearly resectable lesions who have negative or perhaps
      1 or 2 microscopically positive regional lymph nodes.

PMID- 11578372
TI  - Surgical pathologic staging in apparent stage I endometrial carcinoma.
AB  - A multicenter trial on apparent stage I endometrial carcinoma was performed to
      establish an intensive surgical staging, to formulate a treatment on the basis of
      the pathological extent of the disease and to determine the effectiveness of
      adjuvant medroxyprogesterone acetate therapy. The results of the first objective
      on 1,055 patients are herein reported. All patients had total abdominal
      hysterectomy, bilateral salpingo-oophorectomy, colpectomy of the superior third,
      and biopsy of lymph nodes positive or doubtful at radiological imaging or on
      surgical inspection. On the basis of the pathologic extent of the disease,
      patients were classified into five categories: disease outside the uterine corpus
      (RE); disease limited to endometrium (RO); disease with inner myometrial invasion
      and high or moderate grade (R1); disease with deep myometrial invasion or poor
      differentiation (R2); disease with positive retroperitoneal nodes (R3). One
      hundred and forty-six patients were RE, 163 RO, 382 R1, 341 R2 and 23 R3. The
      results showed a clinical understaging in 16% of the cases. According to the new
      FIGO classification, the relapse-free survival at 84 months was 96% for patients
      at stage IA, 92% for patients with stage IB-C, 86% for stage IIA-B, 76% for stage
      IIIA-B and 74% for patients at stage IIIC. These data confirm the importance of
      an intensive surgical staging in apparent stage I endometrial carcinoma.

PMID- 11578373
TI  - The reliability of the histologic diagnosis in colposcopically directed biopsies.
      A plea for LETZ.
AB  - A total of 121 patients with cervical intraepithelial neoplasia (CIN) in their
      punch biopsies were treated by LETZ. In all cases, the transformation zone was
      fully visible and there were no signs of abnormal cylindrical epithelium. The
      final diagnosis was classified in accordance with the histologic report showing
      the most severe lesion. The biopsy diagnosis underestimated the final diagnosis
      in 27 out of the 121 cases. Invasion was present in five out of these 27 cases.
      The discrepancies between the biopsy diagnosis and the final diagnosis were not
      related to the number of colposcopically directed biopsies. It is concluded that
      an important advantage of LETZ, as compared with tissue-destructive techniques,
      is the detection of previously unrecognized invasive disease.

PMID- 11578374
TI  - Proliferating cell nuclear antigen (PCNA) immunoreactivity in ovarian serous and
      mucinous neoplasms: diagnostic and prognostic value.
AB  - Sixty-two serous and mucinous ovarian tumors, an admixture of benign, borderline
      and malignant neoplasms, were immunostained for proliferating cell nuclear
      antigen (PCNA), with the monoclonal antibody PC10. The PC10 index, the proportion
      of cells showing nuclear positive staining, was calculated in each case. All the
      tumors showed positive immunoreactivity for PCNA. There was no overlap of PC10
      counts between benign, borderline and malignant serous tumors but within the
      mucinous group of neoplasms there was considerable overlap between the counts for
      borderline and malignant tumors. There was no relationship between the PC10 index
      and the surgical stage of the malignant neoplasms and the index could not be
      correlated with patient death. Staining for PCNA does not, therefore, appear to
      be of any prognostic value in ovarian adenocarcinomas.

PMID- 11578375
TI  - A comparison of cytology and cervicography in cervical screening.
AB  - The sensitivity and specificity of cervical cytology and of cervicography in the
      detection of CIN and invasive cancer of the cervix were determined in a screening
      programme of an asymptomatic population of 418 women. Because all of the subjects
      were examined colposcopically and biopsies were taken from any suspicious areas,
      the presence or absence of disease was determined by the histology of directed
      cervical biopsies independently of the screening methods being tested.
      Cervicography correctly identified 24 of the 27 women with CIN or invasive
      cancer, whereas cytology detected only 14 (sensitivity of 0.89 vs. 0.52; P <
      0.01). Cervicography detected CIN in 11 women with negative smears, six having
      CIN III. Only one case of CIN I was detected by cytology when cervicography was
      negative. Two cases of CIN II were not detected by either method. Inclusion in
      the analysis of the results from 23 women with technically defective cervigrams
      reduced the size of the difference in sensitivity, but it remained significant
      (0.74 vs. 0.48; P < 0.05). Cervicography was only slightly less specific than
      cytology (0.92 vs. 0.94; NS). Cervicography appears to be more effective than
      cytology in screening for cervical premalignancy but may be more demanding of
      those who perform the test.

PMID- 11578376
TI  - Effect of radiotherapeutic technique on local control in primary vaginal
      carcinoma.
AB  - A retrospective analysis of 73 patients treated for primary vaginal carcinoma
      with radiation therapy was performed to evaluate the effect of radiotherapeutic
      technique on local control. Local control was achieved in five of 22 patients
      (23%) treated with pelvic external beam therapy alone, three of four patients
      (75%) treated with intracavitary cylinder or Bloedorn applicator alone, and 30 of
      47 patients (64%) treated with combination of external beam and brachytherapy.
      Radiation therapy complications requiring hospitalization occurred in six
      patients (8%). A statistically significant difference in local control was
      achieved only when patients receiving external beam and brachytherapy were
      compared with patients receiving external beam therapy alone (P < 0.005). Total
      mid-tumor dose was defined as the sum of midplane tumor dose from external beam
      therapy, mid-tumor dose from interstitial radium needles, and the vaginal surface
      dose from intracavitary radium systems. Total mid-tumor doses ranged from 16 to
      121.7 Gy. Only two of 16 patients receiving less than 55 Gy total mid-tumor dose
      achieved local control. As a result, dividing doses of 45, 55, 65 and 75 Gy
      produced a statistically significant superior local control rate in the patients
      receiving the higher dose (P < 0.01). None of the 16 patients receiving less than
      55 Gy total mid-tumor dose had received brachytherapy. We conclude that the
      combination of external beam therapy and brachytherapy is essential to achieve
      optimal control of primary vaginal carcinoma.

PMID- 11578377
TI  - Radical vulvectomy and groin node dissection in a patient with chronic
      neutropenia-maintenance of leucocyte count using granulocyte colony-stimulating
      factor.
AB  - A patient was referred for consideration of radical surgery in the presence of
      chronic neutropenia. We report the successful maintenance of an adequate
      neutrophil count during the perioperative period using Granulocyte colony
      stimulating factor (GCSF), resulting in successful primary healing of the wounds
      in the absence of infective complications. The use of GCSF in gynecology is
      briefly reviewed.

PMID- 11578378
TI  - Paget's disease of the vulva: the Radiumhemmet series 1975-1990.
AB  - Twenty-eight patients with a diagnosis of 'extramammary Paget's disease of the
      vulva' were referred to the Radiumhemmet, Karolinska Sjukhuset, Stockholm, during
      the period 1975-1990. A clinical and histopathologic retrospective review was
      undertaken. Six patients had associated malignancies (21.4%). The disease was
      considered primary invasive in three cases, whereas three patients later
      developed an invasive cancer. Surgery-local resection, hemivulvectomy or
      vulvectomy-was performed in 24 cases. Twelve patients, in which surgery was
      supposed to be radical with respect to free margins, had a significantly longer
      recurrence-free survival than 12 patients in which the surgical margins were
      dubious.

PMID- 11578379
TI  - Mixed serous-endometrioid carcinoma of the uterus: pathologic and cytopathologic
      analysis of a high-risk endometrial carcinoma.
AB  - A review of the pathology and cytopathology of 295 endometrial adenocarcinomas
      treated surgically at King Edward Memorial Hospital for Women, with full 5-year
      follow-up, revealed 16 cases of pure serous carcinoma (USC), 10 cases of mixed
      serous and endometrioid carcinoma with a predominant serous component (mixed USC
      EAC) and six cases of mixed serous and endometrioid carcinoma with a predominant
      endometrioid component (mixed EAC-USC). The mixed carcinomas may be characterized
      microscopically by classical serous features side by side with classical
      endometrioid features, or additionally by features intermediate between the two.
      Many of these features are reproduced in preoperative cervicovaginal smears. USC
      and mixed USC-EAC were found to be indistinguishable clinically and
      prognostically, with an identical corrected 5-year survival of 40%, although
      numbers are small. Mixed EAC-USC (which contained 10-25% serous differentiation
      in this series), however, were similar in many respects to a control population
      of 95 EAC of Grade 2 and 3. The corrected 5-year survival in these two groups was
      67% and 79%, respectively, which is not statistically significant in this small
      series. This study suggests that the behavior of a mixed tumor containing 50% or
      more serous differentiation is similar to that of pure serous carcinoma, and that
      the behavior of a mixed tumor containing less than 25% serous differentiation is
      similar to that of the other component. Given the poor correlation between
      pathologic findings in curettage and subsequent hysterectomy specimens, however,
      identification of any significant serous element in curettage material may prove
      vital in optimizing surgical and adjuvant therapy.

PMID- 11578380
TI  - Is there a role for CT scanning to monitor therapy of optimally debulked patients
      with advanced ovarian epithelial cancer?
AB  - Sixty patients with optimally debulked stage III ovarian epithelial cancer had
      abdomino-pelvic CT scan preoperatively and after three and six courses of cis
      platin-based chemotherapy just prior to second-look surgery. Pelvic examination
      was performed and serum CA-125 drawn preoperatively, prior to each course of
      chemotherapy and prior to second-look surgery. All pelvic examinations and
      operative procedures were done by the author. Eight additional patients who were
      optimally debulked but whose disease progressed on first-line therapy were
      monitored in a similar fashion. None of 60 patients who underwent second-look
      surgery had evidence of disease on CT scan after three or six courses of
      chemotherapy, regardless of size of residual disease. Routine use of CT scanning
      to monitor therapy following optimal debulking is of little value and may be
      safely omitted.

PMID- 11578381
TI  - Comparison of CO2 laser surgery and loop electrosurgical excision/fulguration
      procedure (LEEP) for the treatment of vulvar intraepithelial neoplasia (VIN).
AB  - The aim of this open clinical trial was to evaluate the therapeutic effectiveness
      of CO2 laser vs. loop electrosurgical excision/fulguration procedure (LEEP) in 28
      patients with vulvar intraepithelial neoplasia (VIN) (mean linear extent = 6
      cm2). To avoid selection bias, in each patient half of the lesional area was
      treated with CO2 laser excision/vaporization and the other half was electro
      excised/fulgurated. All but three patients (89%) were followed for a minimum of 9
      months, maximum 26 months, mean 12 months after last therapy. Complete response
      was obtained in 12 of 25 patients (48%) after a single laser/LEEP most of whom
      had 6 cm2 or less lesional area. Repeated treatments(mean 3) yielded 19 of 25
      (76%) disease-free patients at 9 months or longer. There was no significant
      (chi2) difference between the CO2 laser- or LEEP-treated areas with respect to
      recurrence of disease, healing time (mean 18 days), postoperative discomfort
      (61%) and complications (11%)). The overall operating time when controlled for
      lesional size was twice as fast with the CO2 laser (mean 8 min) than LEEP (mean
      20 min). Laser and LEEP were more suitable for ablational and excisional
      procedures, respectively. LEEP may be an alternative to CO2 laser for treating
      VIN, particularly those with a linear extent less than 6 cm2.

PMID- 11578382
TI  - Malignant germ cell tumors of the ovary: 20-year report of LAC-USC Women's
      Hospital.
AB  - Thirty-six patients with malignant germ cell tumors (GCT) of the ovary were
      treated during the period from 1971 to 1990. Twenty-five of these patients
      underwent initial surgery at this institution; 11 were referred after initial
      surgery. Endodermal sinus tumor (EST) was the most common subtype (N = 13),
      followed by immature teratoma (IMT) N = 11), dysgerminoma (N = 9), and mixed germ
      cell tumor (N = 3). Eight of nine patients with dysgerminoma and 14 of 27
      patients with non-dysgerminomatous germ cell tumors had stage I disease. Surgical
      staging resulted in a change of stage in 10 of 31 patients; seven were upstaged,
      and three were downstaged. Thirty-five of 36 patients are alive with no evidence
      of disease at a median follow-up of 47 months (range 12-210 months). Two of nine
      patients with dysgerminoma received postoperative radiotherapy; two additional
      patients required radiotherapy for recurrence. Twenty-five of 27 patients with
      non-dysgerminomatous tumors were treated with combination chemotherapy. Second
      look laparotomy was done in 18 patients, four of whom had positive results. Three
      of the four patients with positive second-look laparotomy results remain free of
      disease after salvage chemotherapy; the fourth patient died of progressive grade
      3 IMT. Nineteen of 27 patients undergoing fertility-preserving surgery have
      resumed normal menses, and four of these have delivered normal infants. The other
      eight patients remain on oral contraceptives. We conclude that surgical staging
      provided important information in this study of 36 patients with ovarian germ
      cell malignancies. As noted by many previous reports, combination chemotherapy
      (developed during the past 20 years) has dramatically improved prognosis for this
      group of patients. Second-look laparotomy (SLL), especially for patients with
      advanced disease, was able to identify patients requiring additional therapy.
      Most patients with this disease can retain their normal, uninvolved ovary with
      preservation of normal menstrual and reproductive function.

PMID- 11578383
TI  - An evaluation of the prognostic factors in metastatic gestational trophoblastic
      disease.
AB  - A retrospective evaluation of prognostic factors in 55 patients suffering from
      metastatic gestational trophoblastic disease (MGTD) treated by modified
      Bagshawe's CHAMOCA regimen was done. The prognostic significance of the eight
      prognostic factors in the WHO scoring system, number of sites of metastasis and
      FIGO staging were evaluated by univariate analysis using Chi-square test with
      Yates' correction and odds ratio and by multivariate analysis using Cox
      proportional hazard analysis and logistic regression analysis. In the univariate
      analysis, the intervals between antecedent pregnancy and the diagnosis of GTD, (P
      = 0.004) the level of hCG (P = 0.02) and the number of metastatic sites (P =
      0.046) were significantly associated with death. In the multivariate analysis,
      only the interval between the antecedent pregnancy and the diagnosis and the
      level of hCG were significantly associated with death. Thus, it seems that the
      interval between antecedant pregnancy and the diagnosis and the level of hCG were
      the two most significant factors in predicting mortality in high risk MGTD. The
      WHO staging was more predictive of poor outcome than that of the FIGO staging in
      this group of patients.

PMID- 11578384
TI  - Peritoneal adenocarcinoma (serous) of Mullerian type: a subgroup of women
      presenting with peritoneal carcinomatosis.
AB  - Peritoneal adenocarcinoma (serous or other subtype) of Mullerian type (PAMT) is
      frequently misclassified as another primary tumor. Peritoneal carcinomatosis in
      women without evidence of a primary site may occur secondary to a number of
      processes. Confusion regarding the nomenclature has made it difficult to
      determine the incidence and natural history of this unique malignancy. Other
      terms used for this tumor include mesothelioma, peritoneal papillary serous
      carcinoma, extra-ovarian serous carcinoma, and normal-sized ovarian carcinoma
      syndrome. Thirty-four patients (33 serous and one endometrioid) were identified
      with PAMT during 1976 through 1988. One hundred and thirty-seven patients
      underwent primary cytoreductive surgery for a preoperative diagnosis consistent
      with ovarian cancer. Twenty-nine (21.2%) were classified as PAMT (5 of the 34 had
      their initial surgery at other institutions). The mean age was 61.4 years. The
      primary symptoms and signs were abdominal pain (68%) and ascites (52%). Twenty
      five (73%) had a preoperative diagnosis of ovarian cancer while the postoperative
      diagnosis was unknown (44%), PAMT (29%), and ovarian cancer (27%). Univariate and
      multivariate survival analysis were performed. Survival was independent of age,
      residual disease, grade, ascites, type of chemotherapy, and second-look results.
      In patients with residual disease < 1.5 cm, extended survival was found in (hose
      with ascites < 1000 ml, residual disease in pelvis only, and small residual
      volume but statistical significance was not obtained. Twenty-eight patients
      received >/=4 courses of chemotherapy after primary surgery. Twelve of 21
      patients (57%) who received cisplatin (CDDP) survived between 23 and 92 months,
      while no patient receiving other chemotherapeutic regimens survived more than 25
      months. The 2 and 3 year survival rate for CDDP was 47% and 33% vs. 14% and 0%
      for other regimens. Optimal cytoreductive surgery was not an independent
      prognostic factor as found in ovarian cancer, probably secondary to unresectable
      peritoneal carcinomatosis. PAMT is sensitive to chemotherapy but only the use of
      CDDP was associated with long term survival. Based on these results, women with
      peritoneal carcinomatosis consistent with PAMT should receive a CDDP-based
      regimen after primary surgery.

PMID- 11578385
TI  - The effect of chemotherapy on the different components of advanced
      carcinosarcomas (malignant mixed mesodermal tumors) of the female genital tract.
AB  - The effect of chemotherapy on the different components of uterine and ovarian
      carcinosarcoma is largely unknown. This report describes six patients with
      advanced carcinosarcoma, five of whom received 4 cycles of doxorubicin and
      ifosfamide (AI) directed at the sarcomatous component of the tumor. Responses in
      these five patients at second-look laparotomy were: one complete response, two
      partial responses (persistence of only the carcinomatous component), one stable
      disease, and one progressive disease (both components still present in both
      cases). Thereafter 4 cycles of a cisplatin-based regimen were scheduled. Response
      to the cisplatin-containing regimen was only evaluated clinically. The sixth
      patient (with no macroscopic disease left after initial surgery) received 6
      cycles of a cisplatin-based chemotherapy from the onset and was found to be in
      complete response at relaparotomy. Median progression-free survival for all
      patients was 15 months and median survival 21 months. A literature survey showed
      that carcinosarcoma differs from adult soft tissue sarcomas with respect to
      responsiveness to chemotherapy. Cisplatin and ifosfamide are active as single
      agents, whereas the response to single-agent doxorubicin seems to be lower. The
      data suggest, however, that superior response rates and increased survival times
      are achieved with cisplatin/doxorubicin-based chemotherapy. The sensitivity of
      carcinosarcoma to cisplatin supports the recent view that carcinosarcoma of the
      female genital tract is possibly a high grade carcinoma with metaplastic
      sarcomatous elements.

PMID- 11578386
TI  - Ovarian transposition in young patients with invasive cervical cancer receiving
      radiation therapy.
AB  - Twenty-two patients with invasive cervical cancer had ovarian transposition.
      Fifteen patients received whole pelvic external radiation therapy via a
      teletherapy unit, and nine patients also received one or two intracavitary
      insertions. Ovarian function was measured by serum gonadotropins, FSH, and LH. We
      were unable to measure gonadotropin levels in four patients because they were
      lost to follow-up after completion of radiation therapy. Five patients developed
      postmenopausal symptoms; in two the ovaries were not shielded and they received
      radiation by lateral ports with an average dose above 2500 cGY. Therefore,
      ovarian function was preserved in seven of 11 patients (64%), all of whom
      received </= 500 cGY with an average dose of 250 cGY to the ovaries via external
      radiation and intracavitary insertion(s). FSH values ranged from 3.3 to 38.8 mlU
      ml-1 (mean = 17.7 mlU ml-1). Two patients developed symptomatic ovarian cysts.
      Ovarian function can be preserved by transposing the ovaries at the time of
      surgery prior to radiation with adequate treatment planning which limits the
      radiation dose to the ovaries to </=300 cGY.

PMID- 11578387
TI  - Carboplatin and chlorambucil combination chemotherapy as treatment for patients
      with ovarian cancer.
AB  - Fifty-six patients with ovarian cancer (three stage IC, nine stage II, 33 stage
      III and II stage IV) were treated with carboplatin 350 mg m-2 i.v. day 1 and
      chlorambucil orally 0.15 mg kgm-1 days 1-7 inclusive, repeated every 28 days for
      eight courses. The regimen was well tolerated and was virtually free of nephro-
      and neurotoxicity. Grade III or IV hematology toxicity occurred in 18 patients
      but only 31 or 330 courses administered were delayed. Of 40 assessable patients
      eight achieved a clinical/radiologic complete response and 17 a
      clinical/radiologic partial response. Actuarial survival at 50 months was 65% for
      stage II patients, 27% for stage III patients and no stage IV patients survived
      beyond 20 months. Forty-two per cent of patients with residual disease less 2 cm
      survived 50 months, compared with 44% of patients with moderate volume (2-5 cm)
      residual disease and 6% of patients with bulk residual disease. This is an
      active, well tolerated regimen. However, only patients with small volume residual
      disease have a significant chance of prolonged survival.

PMID- 11578388
TI  - Human papillomavirus DNA and genotypes: prognostic factors for progression of
      cervical intraepithelial neoplasia.
AB  - A retrospective study of 227 patients presenting with abnormal cervical cytology
      was conducted to investigate the relationship between human papillomavirus (HPV)
      and progression of untreated cervical intraepithelial neoplasia (CIN) lesions.
      All patients had colposcopically directed biopsies for histologic diagnosis. The
      patients were followed cytologically and colposcopically for a mean of 19 months
      (range 6-42 months). Progression of a cervical lesion was defined as progression
      to a higher CIN grade confirmed histologically by directed biopsy. HPV DNA
      detection was done on material remaining from the cervical swabs by the general
      primer polymerase chain reaction (PCR) and type-specific PCR method, which made
      the detection of HPV types 6, 11, 16, 18, 31, 33 and not yet sequenced DNA types
      (X) possible. The presence of HPV DNA increased with the severity of the lesion
      (P < 0.001). In CIN III, a 100% HPV DNA prevalence was found, with HPV type 16
      being the most prevalent type in 75%. Progression was significantly related to
      the presence of HPV DNA, in particular HPV type 16. The percentage of progressive
      disease was 21% in the case of HPV DNA positive lesions (n = 130) and 29% in the
      presence of HPV type 16, whereas HPV DNA negative lesions (n = 97) showed no
      progression. The detection of HPV DNA and HPV genotype can be used to identify
      patients with high-risk cervical lesions, since the presence of HPV DNA and
      genotype 16 in particular are closely related to CIN progression.

PMID- 11578389
TI  - An electronic approach to the detection of pre-cancer and cancer of the uterine
      cervix: a preliminary evaluation of Polarprobe.
AB  - We report on the testing of a prototype of an electronic device for the detection
      of cervix cancer and its precursors, known as the Polarprobe. The device monitors
      three aspects of the cervix tissue; two relate to optical properties and the
      other to dielectric characteristics. The response to tissue stimulation takes the
      form of an energy pattern which, in conjunction with spectroscopic discriminants,
      can be digitized to prepare an algorithm. The pattern algorithms are sufficiently
      characteristic to be afforded names which correspond to tissue states
      recognizable as normal or abnormal by the clinician. On a tissue observation
      basis the previously established recognition algorithms derived from 106
      volunteers produced assessments which related strongly to colposcopy/histology
      diagnoses obtained on 77 additional volunteers. This concordance between
      colposcopy/histology and Polarprobe diagnoses on this primary analysis subgroup
      ranged from 85% on low-grade intraepithelial abnormalities, and 90% on high-grade
      cervical intraepithelial squamous neoplasia, to 99% on invasive cancer. An
      extrapolation of these results suggests false-positive/false-negative rates in
      the order of 10% are achievable with the current Polarprobe device.

PMID- 11578390
TI  - The efficacy of postoperative vaginal irradiation in preventing vaginal
      recurrence in endometrial cancer.
AB  - Between 1960 and 1985 hysterectomy was performed on 811 FIGO stage I and 116
      stage II endometrial cancers which were divided into three groups: low-risk stage
      Ii (grade 1 and 2 lesions confined to the inner third of the myometrium; high
      risk stage Iii (grade 3 and/or invading to the middle third of the myometrium or
      beyond); and FIGO stage II tumors (also high-risk). Hysterectomy was the only
      treatment in 492; in 145 the vaginal vault alone was radiated and in 290 the
      whole vagina, in each instance by an intracavity dose of 60Gy; in 34 of the
      latter high-risk tumors the pelvis received an additional 46Gy by external beam
      therapy. Forty isolated vaginal recurrences were detected; 10 in 308 low-risk and
      22 in 184 high-risk tumors treated by surgery alone, and two and five in 40 low
      and 105 high-risk patients, respectively, who received adjuvant vault
      irradiation. No recurrences followed irradiation of the whole vaginal mucosa in
      163 stage Ii low-risk and 40 stage II lesions and one, 9 years later, in 87 high
      risk stage Iii tumors. Nearly 45% of patients with vaginal recurrence died from
      cancer within 1 year, 77% within 5 years and only 10% survived their recurrence
      10 years. Total vaginal irradiation eliminated vaginal recurrences in low risk
      and reduced the incidence to 2.1% at 20 years after high-risk tumors.

PMID- 11578391
TI  - Nuclear morphometry and DNA flow cytometry as prognostic methods for endometrial
      carcinoma.
AB  - In a series of 227 women with endometrial carcinoma stages I-IV the prognostic
      value of nuclear morphometry and DNA analysis was evaluated prospectively. The
      tumors were also classified according to histologic subtype, degree of
      differentiation (FIGO), and nuclear grade. The DNA analysis (ploidy and S-phase
      fraction) was made using flow cytometry on fresh-frozen tissue. The morphometric
      measurements and the grading of the tumors were done on both fresh-frozen tissue
      and on formalin-fixed and paraffin-embedded tissue. The rate of recurrence for
      the complete series was 14% with 2.2% vaginal metastases. The overall 5-year
      survival rate was 68% and the corrected survival rate 76%. The minimum nuclear
      diameter and the standard deviation (SD) of the maximum nuclear diameter were
      significant and independent prognostic variables in a Cox multivariate analysis
      when analyzed on paraffin-embedded tissue. The nuclear grade was the single most
      prognostically informative variable. A corresponding analysis on fresh-frozen
      tissue showed that the S-phase fraction and the FIGO grading of the tumor were
      significant variables. The morphometric variables and the nuclear grading were
      non-significant prognostic variables. Morphologic changes in tumor cell nuclei
      during the freezing and thawing procedures may explain the loss of prognostic
      information. A combination of DNA index (fresh-frozen tissue) and the mean values
      of the shortest nuclear diameter and the SD of the longest diameter (paraffin
      embedded tissue) gave the best prognostic information vis-a-vis cancer-related
      death in an all-possible-subsets regression analysis.

PMID- 11578392
TI  - Active intralymphatic immunotherapy of uterine cervical carcinoma with viral
      oncolysate: a pilot study.
AB  - A pilot clinical trial was conducted in patients with squamous carcinoma of the
      uterine cervix to evaluate the clinical and biologic effects of active
      intralymphatic immunotherapy (AILI) with allogenic viral oncolysate (VO) prior to
      radiation therapy. Sixteen patients with advanced primary squamous carcinoma of
      the uterine cervix and lymph node metastases underwent bipedal intralymphatic
      injections of VO. VO was derived from lysates of cervical carcinoma cells that
      had been infected with influenza A virus. AILI was repeated after 2 weeks and
      followed one week later by standard or extended-field radiation therapy (RT). The
      first seven patients were treated at one of the three dose levels: 6 mg (three
      patients), 12 mg (three patients) and 18 mg (one patient). Remaining patients
      were treated at the 12 mg dose level. Sixteen patients received 63 injections
      (one patient received three of four doses) of AILI-VO without significant
      toxicity. Eleven patients have died of persistent or recurrent carcinoma with a
      total median survival of 19.4 months. Examination of humoral and cellular
      immunity during AILI-VO showed an increase in the serum liters of antibodies to a
      surface antigen on cervical carcinoma cells and to the influenza virus. Increased
      non-MHC restricted lymphocyte cytotoxicity was exhibited by three of four
      patients treated above the first dose level. Two of the three patients are
      survivors. By contrast, lymphocytes of patients treated with AILI-VO exhibited
      either an increase or a decrease in proliferation responses to cervical carcinoma
      cells. Similarly, post-treatment lymphocytes exhibited either helper or
      suppressor inducer effects on pre-treatment lymphocytes.

PMID- 11578393
TI  - Clinicopathologic study of 16 cases of primary tubal malignancy.
AB  - Sixteen cases of primary carcinoma of the fallopian tube were diagnosed and
      treated at Queen Mary Hospital, Hong Kong from July 1972 to June 1992
      constituting 0.26% of the total gynecologic malignancies seen during that period.
      The average age was 61 years and the most common presenting symptom was abnormal
      vaginal bleeding. Preoperative diagnosis is difficult; in only one case was a
      diagnosis of malignancy made by cervical smear. An adnexal mass was detected in
      13 of the cases (81.3%) either by clinical examination and/or ultrasonography.
      Therapy consisted of surgical resection, usually followed by various combinations
      of adjuvant radiation therapy and chemotherapy. The cumulative survival was 62%.
      In addition to the typical form of adenocarcinoma, one case of squamous cell
      carcinoma and a case of multifocal endometrioid adenocarcinoma were observed. One
      case of an apparently usual form of adenocarcinoma recurred as a heterologous
      malignant mixed Mullerian tumor 2 years after diagnosis. This series further
      emphasises the wide range of differentiation possible in the Mullerian system and
      the variety of neoplasms which may arise from it.

PMID- 11578394
TI  - Anal colposcopy and the diagnosis of anal intraepithelial neoplasia in high-risk
      gynecologic patients.
AB  - The objective of this study was to define the colposcopic features of the normal
      anal canal and of anal human papillomavirus (HPV)-associated lesions, including
      anal intraepithelial neoplasia (AIN), and to correlate the colposcopic impression
      with the final histopathologic diagnosis. A controled colposcopic screening study
      of women considered at risk for HPV-associated anal epithelial abnormalities was
      carried out. All colposcopic assessments included a biopsy with matching
      histopathologic diagnosis. The study group consisted of 213 women who were
      considered at risk of anal HPV infection and AIN. A further group of 50 women,
      who had no previous history of ano-genital HPV infection or AIN and whose recent
      cervical smear was negative were recruited as controls. Informed consent was
      obtained from all patients, and the study was approved by the local ethical
      committee. In the control group of 50 women no AIN was detected. Normal histology
      was obtained in 45/50 (90%) biopsies where normality had been predicted on
      colposcopy. Histologic diagnosis in the at-risk group was normal in 143 (67%),
      subclinical papillomarvirus infection (SPI) in 24 (11%), and AIN of all grades
      (including three cases of early invasive squamous cancer in a field change of AIN
      III) in 46 (22%) patients. Nineteen of 24 (79%) cases of SPI were incorrectly
      predicted as normal on colposcopy, and another one (4%) as AIN I-II. Only four
      (17%) cases of SPI were correctly predicted at colposcopy. Of the 46 cases of
      histologically proven AIN, 26 (56%) were AIN I-II, and 20 (44%) were AIN III.
      Some 50% of AIN I-II were incorrectly predicted as SPI on colposcopy. Of the 20
      AIN III lesions, 15 (75%) were correctly predicted by colposcopy. Three (20%) of
      these lesions contained foci of early invasion, of which in only one case (33.3%)
      was invasive disease suspected at colposcopy. Some 25% (5/20) of AIN III lesions
      were incorrectly diagnosed as AIN I-II at colposcopy. As is the experience with
      colposcopic assessment of the cervix, anal colposcopy predictions correlated well
      with the final histologic diagnosis, at the normal and high-grade AIN ends of the
      spectrum. The colposcopic predictive distinction between SPI and low-grade AIN (I
      II) was less accurate. It was difficult to distinguish early invasive lesions
      within a field change of AIN III, from pure AIN III. In these studies there were
      three cases of early anal squamous carcinoma arising in AIN III lesions, two of
      which were unsuspected clinically.

PMID- 11578395
TI  - Metastatic small cell carcinoma of the endometrium: prolonged remission and
      possible cure following chemotherapy.
AB  - A 54-year-old woman with inoperable metastatic small cell carcinoma (SCC) of the
      endometrium was treated with cisplatin and etoposide chemotherapy on the basis of
      the histologic similarity to pulmonary SCC. The response to treatment was
      monitored using serum neuron specific enolase (NSE) levels. A complete remission
      was obtained with resolution of symptoms and disappearance of the mass. The
      patient is alive and well 4(1/2) years later. Considering the aggressive behavior
      and short survival usually associated with this tumor and the presence of such
      advanced disease, a complete response to chemotherapy was unexpected. It would
      appear that chemotherapy should always be considered in the management of
      metastatic endometrial SCC, even in the presence of large-volume disease.

PMID- 11578396
TI  - DNA-content in endometrial carcinoma of tamoxifen-treated breast cancer patients.
AB  - DNA measurements and histopathologic evaluation were performed in 17 patients
      treated with adjuvant tamoxifen for early breast cancer and who developed
      endometrial carcinoma during or after the tamoxifen therapy. The tumors were
      exclusively characterized by euploid DNA content except for two cases, one mixed
      mesodermal sarcoma, a highly malignant and rare tumor, and one adenocarcinoma.
      Although the use of adjuvant tamoxifen therapy most likely enhances the risk of
      developing endometrial carcinoma, the beneficial effects of adjuvant breast
      cancer treatment is of well-known clinical importance. The hazards of giving long
      term tamoxifen seem to be low since the endometrial tumors were associated with
      low-grade malignancy and euploid DNA pattern.

PMID- 11578397
TI  - Conclusions and recommendations from the Helene Harris Memorial Trust Fourth
      Biennial International Forum on Ovarian Cancer 11-14 May 1993, Toronto, Canada.
AB  - The Helene Harris Memorial Trust organizes biennial international meetings of
      leading clinicians and scientists to discuss progress in the understanding and
      treatment of ovarian cancer. The conclusions of this meeting, together with
      recommendations for future research are published as a guide to others working in
      this field. The 107 conclusions and recommendations presented cover the full
      range of current topics in ovarian cancer research including the biology of early
      and borderline tumors, the relationship of benign to malignant tumors, in vitro
      models, the role of cytokines, genetic epidemiology, oncogenes and tumor
      suppressor genes, allele loss, localization of the BRCA1 gene, DNA ploidy in
      prognosis, the therapeutic use of interferon, platinum and taxoid drugs,
      screening with panels of tumor antigensm immunotherapy and potenial for gene
      therapy.

PMID- 11578398
TI  - Adenoid cystic carcinoma of the Bartholin's gland: the University of Michigan
      experience.
AB  - Adenoid cystic carcinoma of the Bartholin's gland has been encountered in 11
      patients at the University of Michigan Medical Center since 1936. At the time of
      presentation the average age was 48.9 years, the lesion size was between 0.5 to 4
      cm. The presenting symptoms were pain and/or pruritis associated with a solitary
      mass. Early in this series, excisional biopsy was used to treat eight patients.
      The last three patients have been treated with a radical vulvectomy and
      unilateral or bilateral groin lymph node dissection. Local recurrence has
      occurred in five patients and distant recurrence in four patients. In spite of
      the high recurrence rate, 5- and 10-year survival has been high with all seven
      evaluable patients surviving 5 and 10 years. However, adenoid cystic carcinoma of
      the vulva is associated with late recurrences and metastases: three patients were
      dead of disease at 12, 15 and 31 years after initial diagnosis.

PMID- 11578399
TI  - Treatment of advanced carcinoma of the vulva with chemoradiotherapy - can
      exenterative surgery be avoided?
AB  - Thirty-seven patients with advanced FIGO stage (17 stage III, 20 stage IV)
      carcinoma of the vulva whose extent of disease would have required extenterative
      surgery were treated with chemoradiotherapy (CRT). Radiotherapy was given as a
      split course (2500 cGy mid-plane dose in 10 daily fractions, repeated 1 month
      later) to the first seven patients. Subsequently radiotherapy was given as a
      continuous course (4500 cGy mid-plane dose in 20-25 daily fractions).
      Chemotherapy included mitomycin c as an intravenous bolus and 5 fluorouracil as a
      continuous intra-venous infusion over 4-5 days, with variations in timing and
      dose according to the type of radiotherapy course. Fifteen (47%) complete and 11
      (34%) partial responses were seen at 3 months after completion of treatment. Of
      the 15 patients with complete response, 10 remained disease-free for a median of
      24 months (range 6-36 months). The median sur-vival for complete and partial
      responding patients was 15 and 11 months, respectively (range 2-37 months). Acute
      toxicity included moist perineal desquamation, diarrhea and myelosupression. One
      death secondary to neutropaenic sepsis occurred in the split course group. WHO
      grade 3 radiation enteritis occurred in one patient (14%) in the split course and
      two patients (6%) in the continuous CRT groups. Using CRT, very high response
      rates have been obtained with relatively low toxicity. There is a useful role for
      CRT in the treatment of patients with locally advanced recurrent disease although
      its place in the management of extensive primary disease requires further
      evaluation.

PMID- 11578400
TI  - CA 125 in serum and tumor from patients with uterine sarcoma.
AB  - Serial serum samples of 33 patients with primary sarcoma of the uterus were
      analyzed for CA 125 and frozen tissue sections of tumor from 23 patients were
      tested for this antigen. Before treatment, 12 of 30 evaluable patients showed
      serum CA 125 levels> 16 Uml-1 (40%). There was no relationship between serum CA
      125 level and the histologic subtype. Patients with serum CA 125> 16 Uml-1 showed
      extrauterine tumor sites in 67% of the cases versus 33% in patients with normal
      CA 125 determinations (P = 0.026). In (FIGO) stages I and II, elevated serum CA
      125 levels prior to surgery were associated with a poor prognosis (P = 0.043).
      Patients with recurrent or progressive disease demonstrated serum CA 125 levels>
      16 Uml-1 in 14 of the 20 cases (70%). Sarcoma cells were completely negative for
      CA 125, whereas positivity was observed in the epithelial component of mixed
      Mullerian tumors. The source of the elevated serum CA 125 levels in patients with
      uterine sarcoma may be stimulated mesothelial cells.

PMID- 11578401
TI  - Denser trabecular bone in women with endometrial carcinoma.
AB  - Bone mineral density (BMD) was measured in the distal radius of patients with
      endometrial carcinoma (EC). The patients were classified into two subgroups
      depending on whether earlier hormonal replacement therapy (HRT) was given. Two
      groups of women were recruited as controls: patients with post-menopausal
      bleeding for non-malignant reasons (hospital controls) and healthy women, free of
      gyn-ecologic symptoms (non-hospital controls). The BMD was significantly higher
      in the cancer patients and also in the hospital controls than in the non-hospital
      controls. When several possible confounding factors were checked for in a
      multivariate analysis, BMD still differed between the groups. This could lend
      support to the hypothesis that patients with EC may have an altered endogenous
      endocrine status which eventually affects their bone mass. The results also
      stress the importance of using strictly defined, healthy women as controls.

PMID- 11578402
TI  - Immunohistochemical determination of estrogen and progesterone receptors and DNA
      flow cytometry in endometrial cancer.
AB  - Estrogen and progesterone receptor contents (ER, PR) were assessed by an
      immunohistochemical method and DNA ploidy and S-phase by flow cytometry in frozen
      endometrial cancer tissue sections from 39 cases. Comparison of the
      immunohistochemical and cytosol assays showed 81% and 84% concordance in ER and
      PR contents, respectively. An aneuploid DNA pattern was identified in 30% and a
      high S-phase fraction was found in 33% of 36 specimens studied. Negative ER
      status was associated with aneuploid and high S-phase fraction. A similar
      association was found between PR status and high S-phase fraction. Combined
      analysis of immunohistochemical receptor status and DNA flow cytometry in the
      same sample makes it possible to identify two strong predictive factors in
      endometrial adenocarcinoma.

PMID- 11578403
TI  - Quantitative pathologic features as predictors of long-term survival in patients
      with advanced ovarian cancer treated with cisplatin.
AB  - The prognostic value of morphometric and DNA flow cytometric features were
      studied and compared with FIGO stage, preoperative tumor load, residual disease
      status, Karnofsky index and classic pathologic features such as Broders' grade
      and histologic type in 58 FIGO stage III and IV adequately debulked ovarian
      patients with long-term follow-up. The mitotic activity index, volume percentage
      of epithelium, and mean and SD of nuclear area were assessed by interactive
      morphometry, and tumor material was routinely processed for DNA flow cytometric
      assessment of DNA ploidy and S-phase fraction. Survival analysis (Kaplan-Meier
      curves, Mantel-Cox test), revealed FIGO stage (P = 0.013) and the mean and SD of
      nuclear area to be significant prognosticators (P = 0.027 and P = 0.012,
      respectively). In multivariate survival analysis (Cox model), a multivariate
      combination of FIGO stage, preoperative tumor load and mean nuclear area was the
      best prognostic combination of features (P = 0.0034). These results confirm the
      findings of previous studies. We conclude that, in accord with previous studies,
      morphometric features are good predictors of survival after cisplatin treatment
      in advanced ovarian cancer, especially in combination with FIGO stage and
      preoperative tumor load.

PMID- 11578404
TI  - Long-term survival and prognostic factors in advanced epithelial ovarian cancer
      with special emphasis upon the effects of protocol inclusion.
AB  - The Danish Ovarian Cancer Study Group registered 722 patients in stages III and
      IV during the period 1981-1986. The material included 85% of all ovarian cancer
      patients in the catchment area of the group and patients allocated to protocol as
      well as patients treated outside protocols. Five and 10-year survival were: stage
      III 17%, and 8%, respectively; and stage IV 4% and 2%. Patients allocated to
      protocol had a significantly better survival than patients not included in
      protocols even when only patients younger than 70 years were compared. All non
      protocol patients had a poorer prognosis irrespective of the reason for
      exclusion. Five-year survival for stage III protocol patients was 25% vs. 9%, for
      non-protocol patients younger than 70 years. The 10-year survival was 11% and 4%
      for stage III protocol and non-protocol patients, respectively. A multivariate
      analysis showed that residual tumor, age, stage, and performance status had
      prognostic value. In non protocol patients histologic grade had an additional
      marginal prognostic impact. In conclusion the study showed that the statement
      that long-term survival in advanced ovarian cancer has been increased could not
      be proven by comparison of survival from randomized studies performed in the
      early eighties with survival of stage III and IV patients before the introduction
      of cisplatinum chemotherapy. It is necessary to consider survival of all
      patients, protocol and non-protocol in a geographically well-defined region for
      evaluation of survival improvement.

PMID- 11578405
TI  - Detection and measurement of DNA adducts in the cervix of smokers and non
      smokers.
AB  - Smoking has been associated, on epidemiologic grounds, with an increased risk of
      cervical neoplasia. We have investigated this association, using laboratory-based
      methods. A 32P post-labeling assay was performed on 97 cervical biopsies to
      detect and measure DNA adducts (additional products formed by the covalent
      binding of potential chemical carcinogens to nuclear DNA). The specimens were
      taken from both normal cervices as well as the histologically normal regions of
      cervices with invasive and intraepithelial neoplasia. A detailed smoking history
      was obtained from each patient and correlated with an assay of cotinine level in
      urine. Characteristic smoking-related DNA adducts were found, and a significant
      difference in their levels was detected between current and non-current smokers
      (P = 0.017, Mann-Whitney test). There was also a highly significant trend in
      median adduct levels between the three tissue types (P < 0.002). We conclude that
      the finding of smoking-related cervical DNA damage is suggestive of a causal
      association between smoking and cervical neoplasia.

PMID- 11578406
TI  - The expression of c-erbB-2 (HER-2/neu) oncogene in invasive ovarian malignancies.
AB  - The expression of c-erbB-2 oncogene has been studied in 74 formalin fixed
      paraffin embedded invasive epithelial ovarian malignancies using a monoclonal c
      erbB-2 protein antibody. Only four (5.4%) tumors showed membrane immunostaining.
      FIGO stage, size of residual disease after primary surgery, histologic type and
      tumor grade, were identified by the log rank test as prognostic factors for
      survival. No difference in survival was observed between those with and without
      membrane staining (24 months probability of survival: 50% and 55.4%
      respectively). Our results did not show any adverse prognostic effect of c-erbB-2
      protein expression in our patients.

PMID- 11578407
TI  - Carcinosarcoma of the ovary treated over a 10-year period at the Christie
      Hospital.
AB  - Carcinosarcomas (previously termed malignant mixed Mullerian tumors) are highly
      malignant but rare tumors of the ovary. Most patients have been treated according
      to a wide variety of protocols for soft tissue sarcoma or for epithelial ovarian
      carcinoma and as a result the optimal treatment for this neoplasm is unknown. We
      describe here 20 patients with this ovarian tumor (15 with heterologous
      sarcomatous elements and five with homologous sarcomatous elements) referred to
      our institute. Five patients were treated with surgery alone, two patients with
      chemotherapy alone and 13 patients with a combination of surgery and
      chemotherapy. A variety of chemotherapeutic regimens were used reflecting the 10
      year time span it took to accrue these patients. Forty-five per cent of all
      patients died within 1 year of initial surgery and there was a median survival of
      14 months. Two patients achieved a complete remission following treatment with 10
      cycles of intravenous cyclophosphamide and are still alive at 103 and 106 months
      follow-up. We suggest that a chemotherapy regimen combining cyclophosphamide and
      a platinum analog may be useful for the management of patients with
      carcinosarcoma of the ovary requiring further therapy following surgery.

PMID- 11578408
TI  - Squamous cell carcinoma antigen: pretreatment levels as an indicator of advanced
      or metastatic disease.
AB  - Pretreatment values of squamous cell carcinoma antigen (SCC) were obtained in 100
      consecutive patients with squamous cell carcinoma of the cervix presenting to the
      Regional Gynaecological Oncology Centre in Gateshead, UK. Nine patients deemed to
      have locally advanced disease not suitable for primary surgery had elevated
      levels. Ninety-one patients were suitable for primary surgery. Sixty-seven had
      normal SCC levels, two of which had lymph node metastases. Twenty-four had
      elevated SCC levels, 14 of which had lymph node metastases. Two early recurrences
      have been detected in the raised SCC group where no lymph node metastases were
      present. Elevated levels of SCC in the pretreatment assessment indicate a high
      risk of lymph node metastases and of developing recurrent disease after primary
      surgery.

PMID- 11578410
TI  - Large Loop Excision of the Transformation Zone: A practical guide to LLETZ.

PMID- 11578409
TI  - Fibrosarcoma arising in an ovarian mucinous tumor: a case report.
AB  - A case of an ovarian mucinous tumor with a mural nodule is reported. The mucinous
      tumor was solid and cystic and contained benign, borderline and malignant
      elements. Within the solid area a nodule representing fibrosarcoma was
      identified. Mucocoele of the appendix was the other finding in this case. To the
      best of our knowledge this is the first description of fibrosarcoma arising in an
      ovarian cystadenocarcinoma.

PMID- 11578411
TI  - Hormonal therapy following female genital tract cancer.
AB  - Following treatment of genital tract cancer, women are often left in an estrogen
      deficient state suffering both short- and long-term effects which markedly reduce
      the quality of life. In the belief that sex hormones may induce an adverse effect
      on all these women, attending physicians often refuse to prescribe hormonal
      replacement therapy (HRT). In an attempt to introduce a rational approach to this
      problem the effect of sex hormones on genital tract cancer growth is reviewed and
      some general guidelines for administering sex hormones to women following
      treatment for genital tract cancer are developed. A plea is made to improve the
      well-being of patients following cancer treatment by considering the judicious
      use of appropriate hormonal therapy, including estrogens.

PMID- 11578412
TI  - Surviving gynecologic cancer and coping with sexual morbidity: an international
      problem.
AB  - A review of the international literature reveals that significant sexual
      morbidity occurs for gynecologic cancer survivors, and that there has been little
      reduction in either the incidence or the severity of problems over the last 50
      years available to research. In fact, prospective data from the last 10 years
      highlight the discrepancy in sexual activity and sexual responsiveness and the
      higher frequency of sexual dysfunctions for patients who have been treated for
      gyneclogic cancer in comparison to age-matched healthy counterparts. We conclude
      with an international summary and discuss specific research directions for
      disease sites. We urge international efforts to address quality of life concerns
      of gynecologic cancer survivors.

PMID- 11578413
TI  - Correlation of drug resistance-associated parameters in ovarian tumor biopsies.
AB  - This work compares glutathione levels, glutathione S-transferase activities and
      isoenzyme expression, metallothionein levels and P-glycoprotein expression in
      normal ovaries, and in epithelial ovarian tumor biopsies from patients prior to
      chemotherapy or following relapse. These parameters have been implicated as
      determinants of response to cytotoxic chemotherapy. Large differences were found
      between normal ovary and ovarian tumors, but no significant differences were
      observed between tumors taken before or after cytotoxic chemotherapy. These data
      do not support a role for these biochemical parameters in the decreased response
      seen in patients with recurrent or progressive disease.

PMID- 11578414
TI  - Prognostic importance of DNA-ploidy and S-phase fraction in endometrial cancer.
AB  - On fresh frozen tumor tissue from 161 patients with endometrial cancer DNA-ploidy
      and S-phase fraction were measured in a prospective study to evaluate their
      prognostic and predictive value. All FIGO stage I or II patients had surgery and
      were included in an adjuvant trial comparing tamoxifen 30 mg p.o. versus
      medroxyprogesterone acetate 500 mg p.o. for 2 years versus no therapy. Diploid
      (DNA index (DI) </= 1.1) tumors were found in 75%. S-phase fraction was elevated
      (>5%) in 46 (30%) of the patients. Significant correlations of DNA-ploidy and S
      phase fraction were found with classical parameters such as stage, grade,
      histologic type and estrogen and progesterone receptor status. Patients with FIGO
      stage I aneuploid tumors showed significantly shorter disease-free interval (DFS)
      and overall survival (OAS). Recurrences and deaths occurred more often in tumors
      with raised S-phase fraction. In these early stages clinical outcome was worst if
      both factors were unfavorable. In multivariate analysis of stage I tumors DNA
      ploidy and S-phase fraction were independent of grade, type and estrogen receptor
      status. Patients whose tumors had elevated S-phase fractions (>5%) gained more
      benefit from endocrine treatment than patients with low S-phase fractions.
      Patients with diploid and aneuploid tumors had prolonged DFS and improved OAS, if
      they had received adjuvant hormonal therapy. In endometrial cancer, DNA-ploidy
      and S-phase fraction are objective and reliable prognostic and predictive
      parameters which should be integrated into the clinical management.

PMID- 11578415
TI  - Micro-invasive squamous cell carcinoma of the cervix: a clinico-pathologic study
      of 200 cases with long-term follow-up.
AB  - The clinico-pathologic details of 200 patients with micro-invasive squamous-cell
      carcinoma of the cervix have been analyzed. All tumors invaded 5 mm or less below
      the basement membrane. One hundred and nine were categorized as FIGO stage 1a1
      (early stromal invasion) and 91 as FIGO stage 1a2 (micro-carcinoma). The
      horizontal spread (length) of 12 micro-carcinomas exceeded 7 mm. Twenty-three had
      stromal invasion 3 mm or more, and 22 had capillary-like space involvement. Fifty
      eight patients underwent pelvic lymphadenectomy in addition to hysterectomy and
      none had positive nodes. Univariate and multivariate analyses of possible
      prognostic factors including depth, horizontal spread, width, area, volume,
      grade, growth pattern, capillary-like space involvement, and stromal reaction
      failed to show any to be significantly associated with recurrence. The median
      duration of follow-up is now 8 years (0-22 years). Despite complete resection,
      seven (3.5%) patients developed recurrence of in situ or invasive carcinoma
      (three after early stromal invasion and four after micro-carcinoma), all of which
      were located at the vaginal vault. There were two deaths, one due to pulmonary
      squamous-cell carcinomatosis 21 years after early stromal invasion, the
      connection being tenuous, and the other due to local recurrence. There have been
      no recurrences to date in 23 patients treated by conization alone. The uniformly
      good prognosis of patients in this study is attributed to meticulous sampling of
      operative specimens resulting in accurate diagnosis and appropriate treatment,
      which may be conization alone provided the margins are free, there is no
      capillary-like space involvement, and the depth of penetration is less than 3 mm.

PMID- 11578416
TI  - Stage II adenocarcinoma of the endometrium treated by two standard regimens of
      combined preoperative irradiation and surgery.
AB  - We retrospectively analyzed 77 patients with stage II endometrial carcinoma
      treated with standard regimens of preoperative radiotherapy (RT) and surgery (S).
      The age range was 31-74 years with a median of 56.3 years. Thirty-three patients
      received 40 Gy whole pelvis RT followed by either radical or modified radical
      hysterectomy. Forty-four patients received 50 Gy whole pelvis RT and sequential
      intrauterine and intravaginal cesium-137 brachytherapy followed by a simple
      hysterectomy. Median follow-up was 111 months. No patient was lost to follow-up.
      The overall 5-year actuarial survival was 78%. There was no significant
      difference between the two treatment groups. Several prognostic variables were
      analyzed. Those with histologic grade I and II had 5-year survival of 89% and
      83%, respectively, compared to 62% for grade III (P =0.045). The 5-year survival
      for microscopic cervical involvement was 87% compared to 59% for gross
      involvement (P= 0.008). Patients with negative or microscopic residual tumor in
      the surgical specimen and those with negative lymph nodes had less risk of
      treatment failure. Local failure occurred in only 9%. Major complications (3%)
      were seen only in the radical surgery group. Combined preoperative RT and S
      provide high cure rates with minimal complications for patients with stage II
      endometrial carcinoma. Patients with adverse prognostic factors are candidates
      for trials of more aggressive local and systemic therapy.

PMID- 11578417
TI  - 'Moderate-risk' ovarian cancer (stage I, grade 2; stage II, grade 1 or 2) treated
      with cisplatin chemotherapy (single agent or combination) and pelvi-abdominal
      irradiation.
AB  - We placed patients with invasive epithelial ovarian cancer into four distinct
      prognostic groups: 'low', 'moderate', 'high' and 'extreme' risk. The 'moderate
      risk' group contained all residual negative, stage I and II patients with two
      exceptions: stage Ia or b, grade 1 cancers and grade 3 cancers. They were treated
      with primary surgery, usually including bilateral salpingo-oophorectomy,
      hysterectomy and omentectomy. Chemotherapy was then given (cisplatin at 100 mg m
      2 every 2 weeks for three cycles) followed by pelvi-abdominal irradiation (2250
      cGy in 10 fractions to the pelvis and 2250 cGy in 22 fractions to the whole
      abdomen including pelvis). An early cohort with ascites or positive washings
      instead received six cycles of cisplatin and cyclophosphamide at 75 mg m-2 and
      600 mg m-2 every 4 weeks with the same pelvi-abdominal irradiation sandwiched
      between cycles 3 and 4. One-hundred and nine patients were treated between
      November 1983 and December 1989. Median follow-up was 4.7 years (range 0.7-9
      years). The 5-year actuarial overall and failure-free survivals were 81% and 76%,
      respectively. Chronic toxicity, although usually minor, included 15% with
      peripheral neuropathy or ototoxicity and 23% with chronic abdominal complaints.
      Our combined-modality results are similar to those obtained by other centers
      utilizing either pelvi-abdominal irradiation alone or cisplatin-based
      chemotherapy alone.

PMID- 11578418
TI  - Treatment of cervical intraepithelial neoplasia reverses CD4/CD8 lymphocyte
      abnormalities in peripheral venous blood.
AB  - Immunosuppressed patients have an increased prevalence of cervical
      intraepithelial neoplasia (CIN) and apparently normal subjects with CIN have
      evidence of immunosuppression. The immunosuppression may antedate the cervical
      lesion or be a result of the CIN. One index of an impaired immune response is a
      reduced ratio of CD4/CD8 peripheral blood lymphocytes. This study sought to
      confirm that patients with CIN had a reduced CD4/CD8 ratio and to determine
      whether local treatment of the cervical lesion affected the abnormality. Patients
      with CIN had a lower mean CD4/CD8 ratio than controls (1.19 vs. 1.83, P < 0.01)
      and more of the patients with CIN had a ratio less than 1.0 [14/38 (37%) vs. 1/30
      (3%), P < 0.01]. After laser treatment of CIN, the mean CD4/CD8 ratio was higher
      than before treatment (1.76 vs. 1.19, P < 0.01). Paired pre- and post-treatment
      values in 11 patients confirmed this improvement (mean CD4/CD8: 1.14 vs. 2.08, P
      < 0.01). These findings confirm an association between CIN and a reduced CD4/CD8
      ratio. The effect on lymphocytes of treating CIN suggests that the altered ratio
      is a result of the disease rather than a pre-existing etiologic factor.

PMID- 11578419
TI  - Squamous cell carcinoma of the vagina in a male pseudohermaphrodite with 5alpha
      reductase deficiency.
AB  - A 50-year-old Spanish male pseudohermaphrodite (karyotype 46, XY) is described,
      who had a squamous cell carcinoma of the vagina, FIGO stage IV B. He was reared
      as a girl and changed gender at puberty. The phenotype was typical for 5alpha
      reductase deficiency, as were the laboratory findings. A radical vulvectomy and
      dissection of the groins revealed inadequate resection near the urethra.
      Postoperative external irradiation was given. Human papillomavirus 16 DNA
      sequences were found in the tumor and in a groin metastasis. He died 3.5 years
      postoperation because of a tumor of the lung, probably a metastasis, without
      signs of local recurrence. Some 60 male pseudohermaphrodites due to 5alpha
      reductase deficiency have been described. Many of them had to cope with the
      traumatic experience of a change of gender at puberty, because early gonadectomy
      was seldom done. The sex-life and family-life of our patient were unsatisfactory.
      We recommend early gonadectomy to prevent virilization at puberty. Psychologic
      care, genetic counseling and corrective surgery of the genitalia are necessary.
      Although there are predisposing factors, testicular malignancies have not been
      reported. This is the first report of squamous cell carcinoma of the vagina in a
      male pseudohermaphrodite with 5alpha-reductase deficiency and human
      papillomavirus 16 DNA sequences.

PMID- 11578420
TI  - The additional prognostic value of morphometric nuclear arrangement and DNA
      ploidy to other morphometric and stereologic features in endometrial
      hyperplasias.
AB  - Earlier studies have shown that morphometric analysis of nuclear size and shape
      features and stereologic analysis of gland architecture in endometrial
      hyperplasia are useful to predict the risk of progression to cancer. A
      multivariate discriminatory D-score using these features has a higher sensitivity
      than qualitative microscopic characteristics (nuclear atypicality and glandular
      complexity) when an appropriate threshold is chosen. In the present study, the
      (additional) prognostic value of morphometric features related to the arrangement
      of nuclei in glands (distance of nuclear centroids to basal membrane, angle of
      longest nuclear axis with basal membrane) and DNA-ploidy (determined by flow
      cytometry) has been analyzed in 39 cases of endometrial hyperplasia, seven (18%)
      of which have progressed to cancer. Variation in stratification of nuclei has
      prognostic value, in contrast to DNA-ploidy. Multivariate analysis selects the
      outer surface density of the glands, mean distance, volume percentage of lumen
      and the coefficient of variation of nuclear axes as having separate and
      additional value. A multivariate rule called HYPER-score results from these
      features. With this score a high-risk (score value >/=0.20, nine cases, 78%
      progressed) and a low-risk group (score value <0.20, 30 cases, none progressed)
      can be discerned. The prognostic value, sensitivity and specificity of the hyper
      score greatly exceeds that of any of the previously described prognostic factors
      in endometrial hyperplasias. An additional clinical advantage is that with the
      HYPER-score two groups (instead of four groups as with Kurman's method(1)) with a
      high sensitivity and specificity can be discerned. The morphometric and
      stereologic features agree well with the usual qualitative predictors but have
      much stronger prognostic value.

PMID- 11578421
TI  - Phenotypic characteristics of mononuclear cells in human ovarian tumors - with
      special reference to cystic and ascitic fluid.
AB  - The occurrence of mononuclear cells and their cell-surface phenotype was studied
      in cryo- and paraffin sections in 26 untreated ovarian tumors and in normal
      ovarian tissue. T cells (positive for CD4 or CD8 markers) were sparsely
      represented in all sections of normal ovarian tissue and benign ovarian tumors,
      and in most ovarian cancer sections. B cells were found in three malignant
      tumors, CD57-positive (natural killer) cells in two, and CD25 (interleukin-2
      receptor)-positive cells in one. Macrophages occurred sparsely both in normal
      ovarian tissue and in benign and malignant ovarian tumors. One endometrioid
      ovarian cancer, however, manifested rich infiltration of T cells (predominantly
      positive for CD8 marker). Cystic fluid from malignancies manifested higher
      prostaglandin concentrations and total cell counts than did benign cystic fluid,
      but sparse lymphocytes as a rule (5-10% of the total cell count). As compared to
      cystic fluid, ascitic fluid had higher concentrations both of prostaglandins and
      cells, with up to 25% lymphocytes in connection with malignancies. Immunogenic
      activity thus would appear to be weak in ovarian cancer. The harvest of tumor
      infiltrating lymphocytes (TIL) from cystic fluid in ovarian cancers is moderate,
      compared to that of tumor-associated lymphocytes (TAL) from corresponding ascitic
      fluid samples.

PMID- 11578422
TI  - Correlation between clinical and histopathologic risk factors and lymph node
      metastases in early endometrial cancer (a multivariate analysis of 183 cases).
AB  - This study includes 183 patients with clinical stage I endometrial cancer
      subjected to peritoneal cytology, total abdominal hysterectomy, bilateral
      salpingo-oophorectomy, bilateral pelvic and para-aortic lymphadenectomy and
      omental biopsy during a 12-year period in a single institution. The factors
      analyzed were age, menopausal state, cell type, grade, mitotic activity,
      myometrial invasion, lymphovascular space invasion, cervical involvement,
      microscopic vaginal metastases, adnexal metastases, peritoneal cytology, presence
      of concomitant endometrial hyperplasia and lymph node status. The overall
      incidences of pelvic and para-aortic lymph node metastases were found to be 15.3%
      (28/183) and 9.3% (17/183), respectively. In five of 17 patients (29.4%) with
      para-aortic nodal metastases, pelvic nodes were free of tumor. The most
      significant prognostic factors for positive pelvic and/or para-aortic nodes were
      found to be the depth of myometrial invasion, grade of tumor and age.

PMID- 11578423
TI  - Surgical staging for epithelial ovarian tumors of low malignant potential.
AB  - From January 1975 to December 1991, 34 patients with a diagnosis of epithelial
      ovarian tumors of low malignant potential (LMP) were admitted to the Istituto
      Nazionale Tumori of Milan. Eighteen of them (group 1) underwent complete staging
      laparotomy and retroperitoneal para-aortic and pelvic lymphadenectomy, as for
      ovarian cancer. In the remaining 16 cases (group 2), the surgical treatment
      ranged from unilateral oophorectomy to incomplete staging procedure. In group 1,
      nine patients (50%) were found to have retroperitoneal nodal involvement. In
      group 2, all patients had stage I disease. Patients were followed up for 20-222
      months (mean 108, median 86). There were two recurrences in group 2 (after 5
      years) and none in group 1 (NS). Currently all patients are alive and disease
      free. Nine of 18 group 1 patients were upstaged to stage III on the basis of
      lymph node involvement only. However, at least in this retrospective series,
      lymph node metastases did not affect prognosis or survival.

PMID- 11578424
TI  - Neither toxicity nor dose intensity of carboplatin is affected by glomerular
      filtration rate versus body surface area dose calculation in gynecologic
      malignancy.
AB  - Twelve patients were given 31 courses of carboplatin using a glomerular
      filtration rate (GFR)-based area under the curve (AUC) dose schedule, and nine
      patients were given 35 cycles at a body surface area (BSA) dose of 350 mg m-2
      every 3 weeks. The GFR was determined using technetium-99m-DTPA. The dose given
      was calculated according to AUC, 5 for previously treated and 7 for previously
      untreated patients x GFR + 25. Patients treated using the GFR had a 22% lower
      projected dose intensity (DI) and a 15% lower received DI compared with controls.
      The percentage difference between the received and projected DI was not different
      between the two groups of patients. In 11 of 12 patients treated according to the
      GFR, if the BSA calculation dose had been used it would have resulted in a higher
      dose of carboplatin. Twenty per cent (six of 30 courses) of GFR-based doses were
      delayed compared to 29% (10 of 35) of the BSA-calculated control groups. We
      conclude that giving a dose according to a BSA of 350 mg m-2 leads to a higher DI
      and total dose and does not substantially effect toxicity. It is also cost
      effective as it eliminates the need for unnecessary radiometric GFR
      determination.

PMID- 11578425
TI  - Intestinal operations during surgical procedures for epithelial ovarian cancer.
AB  - Fifty-two intestinal operations were performed during 45 laparatomies in 43 non
      obstructed ovarian cancer patients. The histology of the tumor was serous in
      29/43 cases (67.5%). The gross postoperative morbidity rate was 15.5% and
      postoperative mortality rate 6.9%. The 5-year survival was 28.3%, and was not
      affected by the time of intestinal surgery (during the first or following
      laparotomies). As a result, intestinal surgery in advanced ovarian cancer
      patients is feasible without an undue increase in morbidity. However, it must be
      carefully tailored because, though contributing to the quality of life of these
      patients, it does not seem to affect their survival, at least in this
      retrospective series.

PMID- 11578426
TI  - Carbon dioxide laser vaporization of intestinal metastases of epithelial ovarian
      cancer.
AB  - Purpose To determine the efficacy and morbidity of carbon dioxide laser
      vaporization of intestinal metastases of epithelial ovarian cancer. Patients and
      methods Following maximum surgical cytoreduction, 20 patients were treated with
      laser vaporization of serosal and mesenteric metastases with a carbon dioxide
      hand-held laser at a median wattage of 25 watts using a super-pulse mode. The
      maximum diameter of intestinal metastases ranged from 1 mm to 2 cm and the number
      ranged from 1 to> 100 implants. These patients were compared with 20 matched
      controls. Results Median laser time was 7 min and no patient experienced
      bleeding> 15 ml. Eighteen patients (90%) had no gross residual disease following
      laser vaporization compared to five (25%) of the controls (P = 0.0001). Nineteen
      patients (95%) had no gross intestinal residual disease following laser
      vaporization compared to eight (40%) of the controls (P = 0.01). There was no
      difference in the incidence of postoperative ileus, wound infection or febrile
      morbidity between the groups. No patient in either group developed bowel
      obstruction, perforation, fistula, peritonitis or abscess. Conclusion Carbon
      dioxide laser vaporization of intestinal metastases of epithelial ovarian cancer
      represents intensive cytoreduction which results in superior debulking and does
      not appear to increase postoperative morbidity.

PMID- 11578427
TI  - An albumin-like protein is the major secretory protein of ovarian epithelial
      cells in vivo and in vitro.
AB  - Contemporary experimental techniques were used to evaluate the protein secretion
      of ovarian epithelium. The protein composition of 14 ovarian cyst fluids (OCF)
      from either cystadenomas or cystadenocarcinomas, and conditioned media (CM) from
      seven ovarian carcinoma lines in culture, were analyzed by SDS-PAGE under
      reducing conditions, and Western immunoblots. The major protein common to all the
      above samples was a 65 kDa protein that, by densitometry, constituted between 43%
      and 77% of OCF protein and 19% and 38% of CM protein. By Western blot analysis,
      this band was immunologically related to human albumin. Moreover,
      immunoreactivity to albumin was demonstrated in ovarian epithelium in vivo.
      Ovarian epithelium synthesizes and releases an albumin-like protein that
      constitutes the major secretory protein. This may suggest an osmotic mechanism
      for cyst enlargement in ovarian cystadenomas.

PMID- 11578428
TI  - Different types of rupture of the tumor capsule and the impact on survival in
      early ovarian carcinoma.
AB  - The significance of tumor spill in the early stages of ovarian carcinoma has been
      the subject of controversy. Since rupture of the capsule of the tumor may occur
      in several different ways, we analyzed all cases of early ovarian cancer treated
      at Radiumhemmet, Stockholm, Sweden, during the period 1974-1986, in which
      possible spill of tumor cells was catalogued in different groups. In 247 out of
      394 patients (62%) the risk of spill had to be considered. There was no
      difference in survival between patients whose tumors had intact capsules and
      patients in whom rupture occurred during surgery-78% and 85%, respectively. On
      the other hand, a significant difference in survival was found between patients
      in whom rupture occurred before surgery and those with intraoperative rupture-59%
      and 85%, respectively. The conclusion can be drawn that manipulation during
      surgery which results in puncture or rupture does not have a negative influence
      on the outcome for the patients.

PMID- 11578429
TI  - Vaginal sarcoma: the Royal Marsden experience.
AB  - Six patients with vaginal sarcoma are reported here. This clinicopathologic
      review confirms the poor prognosis of this disease. However, there were three 5
      year survivors, all of whom had early stage disease and low to intermediate grade
      tumors. Apart from tumor grade, stage was of prognostic importance. Late
      recurrences at 5 and 21 years were noted in two of the three 5-year survivors.
      Neither chemotherapy nor radiotherapy were of use in the treatment of late stage
      or recurrent disease.

PMID- 11578430
TI  - The role of vaginal hysterectomy in the treatment of endometrial carcinoma.
AB  - Between 1964 and 1991, vaginal hysterectomy was performed in 60 patients with
      clinical stage I endometrial carcinoma, who were not considered candidates for
      the conventional surgical approach. Of these patients, 66.7% were obese with a
      median weight of 235 pounds. Other risk factors included hypertension (63%),
      diabetes mellitus (34%), cardiac disease (28%) and pulmonary disease (12%).
      Operative mortality was 0%. The complication rate was 14%, with four patients
      requiring transfusions and four patients developing vaginal cuff cellulitis.
      Forty per cent of patients received adjuvant pre- or postoperative radiation
      therapy. Crude survival at 5 and 10 years was 91.1% and 87.1%, respectively.
      However, only one patient died from disease 6 years after primary treatment.
      Although we consider surgical staging as the standard of care for the treatment
      of endometrial cancer, vaginal hysterectomy has a definite place in the
      management of patients with good prognostic criteria who are at high operative
      risk for the standard surgical approach.

PMID- 11578431
TI  - Cervical cytologic abnormalities and negative colposcopy: histologic assessment.
AB  - Colposcopic assessment may be normal in the presence of severe or persistent
      minor cytologic abnormality. To assess the significance of negative satisfactory
      colposcopy in patients with abnormal cervical smears, a retrospective review was
      carried out on 1170 patients who had undergone out-patient loop diathermy
      excision for abnormal cervical cytology. Of these, 69 patients were treated for
      abnormal cervical cytology, despite normal colposcopic findings. Cytologic
      abnormalities ranged from persistent borderline changes to severe dyskariosis.
      Histologic assessment of the excision specimens revealed cervical intraepithalial
      neoplasia (CIN) in 43 (62.3%) cases, of which high-grade CIN accounted for 24
      (34.8%) cases. There was good correlation between cytologic and histologic
      diagnosis. Simple regression analysis showed r = 0.46, P < 0.0001. The cytologic
      abnormality was highly predictive of the corresponding histologic diagnosis. This
      analysis has shown that significant intraepithelial lesions may exist despite
      negative colposcopic examination and highlights the need for histologic
      evaluation in such cases. In these circumstances, loop cone biopsy permits
      accurate definition of lesion severity, avoids potential undertreatment of
      significant lesions and causes less morbidity than conventional cone biopsy.

PMID- 11578432
TI  - Intraoperative frozen section examination of myometrial invasion depth in
      patients with endometrial carcinoma.
AB  - The objective of this study was to evaluate the accuracy of frozen sections (FS)
      as a method for estimation of the depth of myometrial invasion in patients with
      stage I endometrial carcinoma. During a 3-year period (1989-1992), 46 consecutive
      patients with FIGO stage I endometrial carcinoma were included in this study. The
      depth of myometrial invasion was estimated by FS examination performed during
      surgery. The final histologic findings of the surgical specimen were compared to
      the FS evaluation. The results of this study demonstrate that deep or superficial
      myometrial invasions were correctly diagnosed by FS in 42 out of 46 cases
      (91.3%). Three cases (6.6%) with deep myometrial invasion were falsely diagnosed
      as superficially invasive. One case with superficial invasion (2.1%) was falsely
      diagnosed as deeply invasive. In conclusion, intraoperative FS examination of
      depth of myometrial invasion by endometrial carcinoma is a simple and accurate
      method, providing a good correlation with the final histologic report of the
      surgical specimen.

PMID- 11578433
TI  - Isolated skin bridge metastasis following modified radical vulvectomy and
      bilateral inguinofemoral lymphadenectomy.
AB  - Separate vulvar and groin incisions have significantly reduced the morbidity of
      vulvar cancer surgery. We describe a patient with FIGO stage II squamous vulvar
      cancer, who developed an ipsilateral tumor recurrence in the skin bridge between
      the vulva and the groin within 7 months of modified radical vulvectomy and
      bilateral inguinofemoral lymphadenectomy, using triple incisions. The recurrence
      was treated by wide local excision alone and she remains free of disease 2 years
      later. Although rare, the potential for failing to excise tumor emboli in the
      lymphatics of the skin bridge must be recognized when the triple incision
      technique is used in the surgical treatment of vulvar cancer.

PMID- 11578434
TI  - Correspondence.

PMID- 11578435
TI  - Multivariate analysis of factors affecting survival in pelvic exenteration.
AB  - Of 153 patients with primary or recurrent pelvic malignancy referred for
      consideration of exenteration, only 40.6% (62 patients) were found to be suitable
      for exenteration after full assessment. Thirty percent (46 patients) were found
      to be inoperable on examination under anesthesia. Of the remaining 107 patients,
      33% (35 patients) were found to be inoperable at laparotomy, 9% (10 patients)
      underwent radical hysterectomy and 58% (62 patients) had an exenterative
      procedure. One patient had no active disease found on final histologic review of
      the exenteration surgical specimen and was excluded, as the aim of this study was
      to look at the prognostic factors affecting survival. There remained 61 patients
      in the exenteration group who were analyzed. The 2-year survival rate was less
      than 2% for patients with inoperable disease, 48% for patients who underwent
      radical hysterectomy and 54.1% for patients who underwent exenteration. The 5
      year survival rate for all patients undergoing exenteration for pelvic
      malignancies was 44% and that for cervical cancer only was 52%. Multivariate
      analysis of patients who had undergone exenteration showed four significantly
      poor prognostic factors influencing survival. They were: (a) aged older than 69
      years, (b) recurrence of the tumor within 3 years, (c) persistent recurrence, and
      (d) positive resection margins.

PMID- 11578436
TI  - p53 gene mutation is rare in human cervical carcinomas with positive HPV
      sequences.
AB  - Chromosome 17p allelic losses and concurrent p53 mutations have been demonstrated
      in various human cancers. We therefore investigated the presence of chromosome
      17p allelic loss and possible concurrent p53 mutation in 29 Korean cases of
      cervical carcinoma by restriction fragment length polymorphism (RFLP) analysis
      and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      over the region from exon 4 to exon 9 of the p53 gene. We also examined the
      expression of p53 in paraffin tissues by immunohistochemical staining and
      determined the incidence of human papillomavirus (HPV) sequences in the same
      tissues by multitype PCR analysis to correlate them to the allelic loss on
      chromosome 17p13 and p53 mutation. In the analysis of 29 cases, loss of
      heterozygosity (LOH) was observed in eight (40%) cases out of 20 informative
      cases and p53 mutation was observed in only one case (3.4%) at exon 5. So in the
      majority of cases with LOH on 17p in this series, mutation of p53 gene appeared
      to be rare. But we obtained three cases (10.3%) of positive immunoreactivity from
      29 cases. Those cases may carry mutations outside of the regions examined by PCR
      SSCP. HPV DNA was detected in 27 of 29 cases (93.1%). HPV types 8, 11, 16, and 18
      were detected in the samples we tested, while only two (7.4%) out of 27 HPV
      positive cases exhibited overexpression for p53 without any demonstrable p53
      mutation upon PCR-SSCP. These results suggest that HPV infection may play a role
      in inactivating wild-type p53 protein in cervical carcinomas. In conclusion,
      mutation and overexpression of p53 gene appear to be rare, particularly in cases
      of cervical carcinoma associated with positive HPV sequence.

PMID- 11578437
TI  - Malignant melanoma of the vulva and vagina: a report of 23 cases presenting in a
      10-year period.
AB  - In the 10-year period ending December 1991, 14 patients with primary melanoma of
      the vulva and nine with primary melanoma of the vagina were diagnosed and
      treated. Of the patients with vulval melanoma, three were treated surgically with
      wide local excision of the tumor alone, six had wide local excision with inguinal
      node dissection, and five had radical vulvectomy with inguinal node dissection.
      Four of the patients with vaginal melanoma had wide local excision; two had wide
      local excision with inguinal and or pelvic node dissection; and three had surgery
      that was more radical than this. Two years after diagnosis, all of the patients
      whose tumors were 2 mm thick or more had died, or were alive but had distant
      metastases. This was independent of the apparent surgical success of local
      excision of the disease. We consider that conservative procedures in the
      management of invasive melanoma of the lower female genital tract should be the
      rule, and that radical procedures should be reserved for palliation rather than
      cure.

PMID- 11578438
TI  - What is the true incidence of primary fallopian tube carcinoma?
AB  - Fallopian tube carcinoma can be histologically indistinguishable from and has a
      similar clinical behavior to epithelial ovarian carcinoma. However, it is
      considerably less common; only approximately 1000 cases have been recorded in the
      literature. In the prevalence screen of 22000 women participating in The Royal
      London Hospital, London, UK, ovarian cancer screening project, three cases of
      early stage primary fallopian tube carcinoma were diagnosed following the finding
      of an elevated serum level of the CA 125 antigen. The ratio of epithelial ovarian
      : tubal cancer developing in these postmenopausal volunteers was 6:1. This is 25
      fold greater than the expected ratio. It is difficult to attribute this finding
      to population selection bias. However, it is possible that the screening test was
      particularly effective in detecting tubal carcinoma or that, in clinical
      practice, the true primary site of origin of some tumors classified as widely
      disseminated ovarian cancer is in the fallopian tube.

PMID- 11578439
TI  - Squamous cell carcinoma of the vagina: a report of 32 cases.
AB  - Between 1982 and 1992, 32 patients with squamous cell vaginal cancer were
      treated. Fourteen patients had stage I, 11 stage II, two stage III and five stage
      IV disease. The mean age of stage I and II patients was 64, of stage III and IV
      patients 73. Six patients were pessary-bearing, two had a total procidentia,
      eight had been treated for cervical intraepithelial neoplasia (CIN), one for
      cervical cancer and one for vulvar cancer 5-21 years before diagnosis. One
      patient had had external irradiation for endometrial cancer 15 years before. Nine
      patients had no follow-up examinations after treatment for CIN, for vulvar cancer
      or after insertion of a pessary. In 14 patients doctors' or patients' delays were
      considerable. Most patients presented with vaginal discharge or bleeding, and
      urinary symptoms. Various treatment modalities were used. The selected patients
      who could be treated by surgery did best. Only patients with a stage I tumor or a
      stage II tumor with a diameter of at most 30 mm survived. Tumor stage and tumor
      diameter were the important prognostic factors. No patient died of disease after
      33 months. Failure in obtaining local control was the usual cause of death.
      Recommendations for prevention or early diagnosis are formulated.

PMID- 11578440
TI  - Carcinoma of the fallopian tube. A clinical and histopathologic review. The
      Radiumhemmet series.
AB  - A histopathologic and clinical review of the Radiumhemmet series of primary
      fallopian tube carcinoma (PFTC) treated from 1923 to 1991 revealed that 128 cases
      fulfilled the diagnostic criteria for PFTC. These cases were staged according to
      the new FIGO staging rules for PFTC. Survival was studied with respect to
      prognostic factors such as age, stage, histologic subgroups, degree of
      differentiation and mode of treatment. The mean age at diagnosis was 56 years.
      Seventy-four per cent were found to be in stage Ia-IIa and 26 % in stage III-IV.
      Forty-five per cent were nulliparous and 22 % had evidence of previous pelvic
      inflammatory disease. Treatment modalities changed during the studied period.
      Thirty-three per cent of patients underwent surgery with total abdominal
      hysterectomy and bilateral salpingo-oophorectomy while 67 % were incompletely
      operated. A trend towards improvement in results was noticed-however, it was not
      statistically significant. Among the 14 prognostic variables tested in the
      multivariate analysis the first in rank were stage (P = 0.001) and degree of
      differentiation of the tumors (P = 0.070). Patients receiving chemotherapy had
      superior survival rates compared with those without chemotherapy (P = 0.0006) and
      patients with cisplatinum-containing chemotherapy did better than those without
      cisplatin.

PMID- 11578441
TI  - Cytologic detection of urinary bladder involvement in cervical cancer.
AB  - One-hundred and four patients with advanced carcinoma of the cervix had their
      urine specimens collected, at the time of cystoscopy, for cytologic detection of
      the presence of malignant cells. Forty-eight (46%) of the patients had evidence
      of bladder mucosal involvement at cystoscopy. The overall sensitivity of urine
      cytology in detecting bladder mucosal involvement was 56%, with a specificity of
      93%. The predictive value for a positive result was 87% and the accuracy of the
      test was 76%. The findings indicate that urine cytology is a useful test for
      detecting bladder mucosal involvement in cervical cancer where cystoscopy is not
      available.

PMID- 11578442
TI  - Prostaglandin-induced cervical dilatation prior to intracavitary radiotherapy for
      carcinoma of the cervix: a pilot study.
AB  - The efficacy of 1 mg 16,16-dimethyl-trans-Delta2 prostaglandin E1 (Gemeprost)
      pessaries in achieving cervical dilatation prior to intracavitary brachytherapy
      was investigated in 16 post-menopausal women with cervical carcinoma. All had
      received external beam pelvic radiotherapy in the preceding 6 weeks. Four
      patients were nulliparous and 12 multiparous (mean parity 1.9). FIGO stages were
      IB (2), IIA (4), IIB (5), IIIA (1), IIIB (3), IVB (1). The cervical os was
      assessed before pessary insertion and again at the time of intracavitary
      insertion. The os was closed in 100% (16/16) of patients before and open in 75%
      (12/16) of patients after pessary insertion. The maximum size of Hegar dilator
      passed without mechanical dila-tation was recorded. Mean cervical dilatation was
      4.25 H (5.5 H in those with a clinical response). The 12 responding patients had
      rapid and uncomplicated procedures with no need for additional mechanical
      dilatation. Both patients in whom attempted mechanical dilatation failed had had
      previous conization of the cervix. The following mild side-effects were reported:
      abdominal cramps (43.8%), headache (12.5%) and fever (6.3%). These data support
      the use of Gemeprost pessaries to achieve cervical dilatation in post-menopausal
      women undergoing intracavitary brachy-therapy following external beam
      radiotherapy.

PMID- 11578443
TI  - DNA-ploidy and mutant p53 overexpression in primary fallopian tube cancer.
AB  - Nuclear DNA content and p53 immunoreactivity were determined in 53 cases of
      primary fallopian tube cancer (PFTC). All tumors showed a distinctly aneuploid
      DNA distribution pattern, whereas p53 immunoreactivity was observed in 51% of the
      cases. If the patients were divided into two groups according to survival time,
      p53 immunoreactivity was present in 40% of the tumors from patients surviving for
      more than 8 years and in 65% of tumors from patients who died within 2 years.
      This difference was not statistically significant (P = 0.438). Patient survival
      was significantly correlated to the clinical stage (FIGO) (P = 0.0009).

PMID- 11578444
TI  - Phase II trial of isotretinoin and interferon alpha-2a in the treatment of
      advanced recurrent cervical carcinoma.
AB  - Background: A recent trial by Lippman et al.16 demonstrated the effectiveness and
      synergy of the combination of interferon alpha-2a and isotretinoin in the
      treatment of patients with locally advanced, previously untreated squamous cell
      carcinoma of the cervix. Purpose: In this phase II trial, we used this
      combination to treat patients with advanced and recurrent squamous cell cervical
      carcinoma, aiming to assess its efficacy in terms of objective responses as well
      as toxicity. Methods: Eighteen patients with advanced recurrent squamous cell
      carcinoma of the cervix were enrolled. All 18 had previously been irradiated. In
      addition, six had received chemotherapy following progression after radiation
      therapy. Treatment consisted of interferon alpha-2a, 6 MU m-2 subcutaneously
      daily, 5 days a week and isotretinoin, 1 mg kg-1 orally, daily, for at least 2
      months, depending on the response or toxicity. Results: All 18 patients (16 stage
      IVA and 2 stage IVB) were considered eligible for response and toxicity
      evaluation. After a median of 3 months (maximum of 8, in responders), we observed
      partial responses in two patients (11%); 95% confidence interval 0-25%. Five
      (27.7%) patients had stable disease. Responses and disease stabilization were
      observed only in the group of patients who had received irradiation alone. The
      median time to progression was 6 months (range 3-8+ months). The toxicity was
      very acceptable in this group of women. Low fever occurred at the beginning of
      the treatment in five patients. Fatigue and weakness were observed in four
      patients and required temporary interferon dose reduction, bone pain in three
      patients, grade 1 leukopenia in two patients and more intensive dry skin in four
      patients. Two patients had slight hypertriglyceridemia. Conclusion: Objective
      responses were observed using the combination of interferon alpha-2a and
      isotretinoin in a group of patients with advanced recurrent squamous cell
      carcinoma of the cervix. We now test this combination in previously untreated
      patients in a neoadjuvant setting.

PMID- 11578445
TI  - Changes in steroid receptor activation, cell kinetics and tumor growth rate,
      during progression of human endometrial adenocarcinomas growing in nude mice: a
      brief review.
AB  - Our findings concerning changes in steroid receptor activation, cell kinetics and
      tumor growth during progression of human endometrial adenocarcinomas
      heterotransplanted into nude mice were reviewed. We found several major changes
      during the course of progression of these tumors. Such alterations as changes in
      estrogen receptor function, post-receptor changes and intratumor endocrine
      interactions were identified. Our results suggest moreover, that development of
      these alterations is probably genetically determined though some of the changes
      may be modified by the level of circulating estradiol concentrations. Through
      influenced tumor progression, the level of circulating estradiol may also affect
      hormone treatment of human endometrial adenocarcinomas.

PMID- 11578446
TI  - The oncogenic potential of Candida in the female genital tract.
AB  - The possible role of Candida species in carcinogenesis at the uterine cervix was
      investigated in 226 females attending a colposcopy clinic. Approximately 34% of
      the 226 subjects harbored Candida species in cervical/vaginal secretions, but
      there was no association with any particular histologic abnormality. Two
      independent analytical procedures were used for strain discrimination of the
      isolates of C. albicans, but again no relationship was found between individual
      strains and histologic diagnoses. Only three C. glabrata strains were isolated,
      but they were all in association with cervical intraepithelial neoplasia (CIN) II
      or III. A total of 18 strains of C. albicans, one C. glabrata and one C.
      parapsilosis all inhibited the formation of the nitrosamine nitrosodimethylamine
      (NDMA) from precursors. Furthermore, C. albicans strains did not convert NDMA to
      carcinogenic metabolites. The results of this study do not suggest that C.
      albicans has a role in cervical carcinogenesis.

PMID- 11578447
TI  - Problems in the use of urinary hCG-beta-core as a tumor marker in gynecologic
      cancer.
AB  - Urinary human chorionic gonadotrophin beta-core (hCG-betaC) was detected in 55
      77% of gynecologic malignancies. The use of spot and early morning urine hCG
      betaC as a tumor marker was explored with regard to the stability of the hCG
      betaC level in serial spot urine samples collected within 24 hours and in early
      morning urine collected over 3 days. Thirteen patients with gynecologic
      malignancies were asked, before treatment, to collect serial urine samples voided
      within 24 hours. Nine of these 13 patients were also asked to save early morning
      urine for 2-3 consecutive days. Their urine was assayed for creatinine and hCG
      betaC using an immunoradiometric assay. Variation of urine concentration was
      corrected by using the hCG-betaC/creatinine (betaC/Cr) ratio expressed in pmolg
      1. Wide fluctuations of betaC/Cr ratios were found both in the serial spot urine
      within 24 hours and in early morning urine within 3 days. Eight per cent of the
      patients had one or more spot hCG-betaC level double or half the median of their
      own serial urine samples. Neither spot urine nor early morning urine hCG-betaC
      were suitable for use as a tumor marker for continuous monitoring because of the
      large fluctuation in hCG-betaC levels. The reason for such a wide fluctuation is
      not clear.

PMID- 11578448
TI  - Multiparameter flow cytometric measurement of epidermal growth factor receptor
      and c-erbB-2 oncoprotein in cultured cells and in fresh and preserved solid tumor
      cells.
AB  - We developed a multiparameter flow cytometric technique for the simultaneous
      measurement of cellular DNA content and c-erbB-2 or epidermal growth factor
      receptor (EGFR) expression. The method provides a high resolution of DNA content
      and well preserved c-erbB-2 and EGFR immunostaining under saturated antibody
      conditions, allowing good control for background fluorescence and satisfactory
      cell morphology. Four different protocols for the short-term preservation of
      cells used for multiparameter flow cytometric assay of EGFR and c-erbB-2 were
      assessed in cell suspensions prepared by mechanical disaggregation in 10
      gynecologic tumors. The protocols at 4 degrees C were: storage in 50% methanol,
      and storage in buffer after formalin fixation. Tissues were also cryopreserved as
      cell suspensions and tissue blocks. When the oncoprotein expression and DNA
      histograms were compared with those in fresh suspensions, cryopreservation was
      found to be the best method: oncoprotein expression was well preserved and there
      was a good correlation between oncoprotein expression and the quality of the DNA
      histograms. The currently developed methods for cell preservation make the
      technique generally available for clinical cancer studies.

PMID- 11578449
TI  - Ureteric obstruction after radical hysterectomy.
AB  - Two patients with invasive carcinoma of the cervix treated with radical
      hysterectomy developed total unilateral ureteric obstruction postoperatively. A
      temporary percutaneous nephrostomy was inserted. Because both patients needed
      adjuvant radiotherapy, intended reimplantation of the ureter was postponed.
      During this period spontaneous passage through the ureter was observed after 5
      and 14 weeks, respectively. It is emphasized that a 'wait and see' policy may be
      justifiable in the case of ureteric obstruction of unclear etiology after radical
      hysterectomy for at least 3 months, as long as renal function is preserved by
      percutaneous nephrostomy drainage of the affected kidney side.

PMID- 11578450
TI  - Multiple primary malignancies in patients with gynecologic cancer.
AB  - A retrospective analysis was made of 1044 patients with gynecologic malignancies
      treated in our department over a 12-year period, in order to review the frequency
      and types of multiple primary neoplasms. Multiple primary neoplasms were detected
      in 45 (4.3%) cases, including 16 (2.1%) out of 733 cervical cancers, 14 (8.2%)
      out of 166 endometrial cancers, three (15%) out of 20 vaginal cancers and 12
      (9.8%) out of 123 ovarian cancers. Fifteen cases were synchronous and the
      remaining 24 cases were heterochronous, with an average 4.9-year interval. The
      most frequent other site of neoplasm was the breast, particularly in patients
      with endometrial or ovarian cancer. We conclude that gynecologic malignancies are
      often associated with primary cancers elsewhere, especially in the breast,
      stomach, colon and thyroid. A patient presenting with a gynecologic malignancy
      should be thoroughly examined for a second cancer, as should patients being
      followed-up after treatment for genital tract cancer.

PMID- 11578451
TI  - Long-term results of sequential postoperative treatment with vincristine,
      bleomycin, mitomycin c, cis-platin and radiotherapy after surgery for high-risk
      patients with cervical carcinoma stage IB-IIA.
AB  - Adjuvant treatment of patients with risk factors after surgery for cervical
      carcinoma remains unsatisfactory. A combination of radiotherapy and chemotherapy
      might improve the control of microscopic metastases. In this prospective study,
      28 patients with risk factors after surgery for cervical carcinoma underwent a
      sequential treatment consisting of two courses of chemotherapy with vincristine,
      bleomycin, mitomycin c and cis-platin (VBMP), followed by radiotherapy with 54 Gy
      to the pelvis and the aortic nodes. Risk factors mainly consisted of nodes
      metastases (25 patients), but patients with parametrial invasion or histologic
      evidence of neoplastic vascular permeation outside the tumor were also included
      in the study. The treatment was well tolerated and all patients received the
      planned dose of chemotherapy and radiotherapy; in the follow-up one patient died
      of ileal necrosis and one died of pulmonary embolism after being medically
      treated for subocclusion. With a minimal follow-up of 70 months, 15 patients are
      alive and free of disease, two have died of complications (one with local
      recurrence), one has died of intercurrent disease and 10 have died of disease
      (six distant, four local). The site of recurrence was outside the field of
      irradiation in six cases (lungs in two cases, liver and para-aortic nodes in one
      and distant nodes in three). This treatment is feasible but control of distant
      metastases in high-risk patients after surgical treatment remains unsatisfactory.

PMID- 11578452
TI  - Infection by human papillomavirus types 6, 11, 16, 18, 31, 33 and 35 of the
      cervix in Japanese women.
AB  - Exfoliated cervical cells from 321 Japanese women were examined for human
      papillomavirus (HPV) DNA types 6, 11, 16, 18, 31, 33 and 35 using polymerase
      chain reaction (PCR) and dot-blot hybridization methods. HPV DNA was present in
      9.3% of patients with normal cervixes, 72.7% of patients with cervical
      intraepithelial neoplasia (CIN) and 77.8% of patients with invasive carcinoma.
      Younger patients (</=29 years) with normal cervixes had a 18.5% incidence of HPV
      DNA, whilst similar older patients (>/=50 years) had a 1.9% incidence, a
      significant difference (chi2= 6.478, P < 0.01). In the CIN I and II groups, an
      incidence of 11.1% of types 16 and 18 was found, while in the CIN III or invasive
      carcinoma group the incidence was 58.1%, again a significant difference (chi2 =
      12.075, P < 0.01). Furthermore, persistence or progression of CIN showed a
      significant correlation with infections by types 16 and 33 (chi2= 4.904, P <
      0.01). However, no significantly different incidence of HPV infection was found
      between the CIN and the invasive carcinoma groups. It is suggested that (a)
      younger patients with normal cervixes have a higher incidence of HPV infection
      than do older patients; (b) HPV types 16, 18 and 33 are important etiologic
      agents of CIN III and invasive carcinoma, as well as in the persistence and
      progression of CIN; (c) progression of CIN to invasive carcinoma may depend on
      factors other than HPV infection in the cervix.

PMID- 11578453
TI  - Combination of new biologic parameters as a prognostic index in epithelial
      ovarian carcinoma.
AB  - In a total of 77 patients with epithelial ovarian carcinomas, new biologic
      parameters [estrogen and progesterone receptor (ER, PR), DNA-ploidy (DP), S-phase
      fraction (Spf), cycling index (Ki67), Her2b/neu oncoprotein, epidermal growth
      factor receptor (EGF-R), cathepsin D and P170 glycoprotein] have been
      simultaneously detected and correlated to the clinical outcome [progression-free
      (PFI) and overall survival (OAS)] in a preliminary study. Apart from conventional
      prognosticators (age, stage, grade, residual tumor) and the postoperative serum
      marker Ca125, DP (P = 0.01), Spf (P = 0.009), Ki67 (P = 0.05) and PR (P = 0.01)
      could predict a short OAS (log rank test), whereas cathepsin D was of borderline
      significance only. Prognostic significance could be improved by using
      combinations of different factors [two markers of differentiation (DP, PR), one
      marker of proliferation (Spf) and one marker describing local tumor spread
      (cathepsin D)]. The difference in prognosis between patients with either all or
      three favorable tumor factors and patients with two to four unfavorable tumor
      factors reached a similar significance as can be obtained using FIGO stage as a
      prognostic factor (P = 0.007 for PFI, P = 0.0005 for OAS). These results were
      similar if early stages (FIGO I and II) were excluded. However, in a Cox
      regression analysis, including stage and residual tumor, this combination was
      significantly independent for PFI and OAS and could give additional information.
      Therefore, the large number of new biologic tumor markers could be restricted to
      only a few significant prognosticators to predict prognosis in primary epithelial
      ovarian carcinoma. In the future tumor characterizations may allow more
      individualized treatment with more aggressive, or even without, cytotoxic therapy
      after primary surgery.

PMID- 11578454
TI  - Bleomycin, ifosfamide and cis-platin chemotherapy in recurrent and persistent
      cervical cancer, a prospective study.
AB  - Thirty patients with histologically proven recurrent or persistent squamous cell
      cervical carcinoma were treated with chemotherapy, consisting of a combination of
      bleomycin, ifosfamide and cis-platin (BIP). All patients were evaluable for
      response. An objective response was seen in nine of the 30 patients (30%):
      complete in two (6.7%) and partial in the other seven (23.3%). A total of 39
      tumor sites was treated: five responses were observed in 26 irradiated areas
      (19%), whereas seven responses were observed in 13 nonirradiated areas (53.8%).
      Side-effects were mainly nausea, vomiting, alopecia, myelosupression, fever and
      impaired renal function. Encephalopathy was recorded in four patients (severe in
      one). No patient died from the toxic effects of chemotherapy. The results
      indicate that BIP is an active combination in recurrent and advanced cervical
      carcinoma, with acceptable toxicity; however, this combination failed to prove
      any superiority over other single or multi-drug treatments proposed in the last
      decade.

PMID- 11578455
TI  - Monoclonal origin of endometriotic cysts.
AB  - Endometriosis-endometrial tissue in an ectopic site outside the uterus-is one of
      the most common gynecologic disorders. The pathogenesis of this disease is
      controversial; the two major theories implicate either metaplasia or metastatic
      spread. In the ovary, endometriosis sometimes appears as endometriotic cysts.
      Occasionally, malignant tumors develop within these cysts, which therefore have
      been suggested to carry a neoplastic potential. We have investigated the clonal
      origin of five such ovarian cysts by a recombinant DNA X-chromosome inactivation
      technique. Three of the endometriotic cysts showed a monoclonal X-chromosome
      inactivation pattern, ie the cell populations of those cysts were each derived
      from one cell, whereas the remaining two cysts had polyclonal inactivation
      patterns. These findings suggest that endometriotic cysts can, in at least some
      cases, be regarded as neoplasic.

PMID- 11578456
TI  - Previous hydatidiform mole identified as the causative pregnancy of
      choriocarcinoma following birth of normal twins.
AB  - For appropriate clinical management of patients with gestational trophoblastic
      tumors it is important to ascertain both the nature of the causative pregnancy
      and the time interval between that pregnancy and the diagnosis of the tumor. It
      has been shown that the immediately antecedent pregnancy may not be the causative
      pregnancy in some cases of choriocarcinoma, particularly where there is a history
      of molar pregnancy. We report further studies of a case where the causative
      pregnancy was shown to be a hydatidiform mole, not the immediately antecedent
      normal term pregnancy. We describe the use of the polymerase chain reaction (PCR)
      to amplify short tandem repeat polymorphisms in DNA prepared from pathologic
      blocks of the patient's previously recognised molar pregnancy. A comparison of
      these polymorphisms with those in the parental and tumor DNA has enabled us to
      confirm that this hydatidiform mole was indeed the causative pregnancy. Molecular
      genetic techniques provide a rapid method of determining whether a
      choriocarcinoma is gestational and, if so, identifying the causative pregnancy.

PMID- 11578457
TI  - Euthanasia: a personal experience in gynecologic oncology.
AB  - Euthanasia means the active causation of death by a life-shortening medical act
      performed on a seriously ill patient who has a concrete expectation to die. The
      request for euthanasia has always existed. In medical ethics the value of the
      protection of human life and the value of respect for the desire to die in
      dignity are both standards of equal order. In the process of euthanasia the wish
      of the patient is the most important. It is the responsibility of the doctor in
      attendance to keep all the personnel involved very well informed about the wishes
      of the patient, to prevent difficulties in the process of decision making. One
      has to realize that the emotional burden assumed by the doctor and nurses is very
      important. They become involved in the process of taking leave but have to give
      priority to their task as caregivers. Euthanasia can take place only as a part of
      terminal care which is given with much effort and personal concern.

PMID- 11578458
TI  - Sebaceous carcinoma arising within an ovarian cystic mature teratoma.
AB  - A 77-year-old woman presented with an abdominal swelling and underwent a total
      abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy for a
      left ovarian tumor. This was an ovarian mature cystic teratoma in which had
      developed a sebaceous cell carcinoma. This is a rare form of ovarian malignancy
      whose behavior is poorly documented. The treatment and follow-up of this case are
      discussed.

PMID- 11578459
TI  - Weekly cisplatin +/- glutathione in relapsed ovarian carcinoma.
AB  - On the basis of experimental data showing the efficacy of glutathione (GSH) as a
      protective agent on cisplatin-induced neurotoxicity and the clinical evidence of
      the low incidence of neurotoxicity in high-dose cisplatin + GSH treated patients
      we evaluated the neuroprotective effect of GSH in a randomized phase II study.
      Thirty-three patients with relapsed ovarian cancer after a disease-free interval
      of at least 1 year and a cumulative dose of prior cisplatin ranging 450-650 mg m
      2 were randomized to receive cisplatin 50 mg m-2 weekly +/- 2.5 g GSH for 9
      consecutive weeks. Clinical and instrumental neurologic and otologic evaluations
      were made at the baseline and at the end of the study. Overall response rate in
      31 evaluable patients was: 9/15 in group A and 12/16 in group B, including 4/15
      vs 7/16 complete responses. The administered dose intensity of cisplatin was
      higher in the GSH treated patients (100% dose intensity was received by 56% vs
      27%). A trend in terms of neuroprotection was detected in the GSH treated group,
      and no major difference was observed in the other toxicities between the two
      groups. It is concluded that possible benefit can be expected from the
      concomitant administration of GSH and cisplatin in patients at high risk of
      developing neurotoxicity, without decreasing the anti-tumor activity.

PMID- 11578460
TI  - Identification of small areas of solid growth has a strong prognostic impact in
      differentiated endometrial carcinomas. A histopathologic and morphometric study.
AB  - A large, consecutive series of 562 patients with endometrial adenocarcinomas was
      investigated with respect to prognostic factors. In the histopathologic
      evaluation the World Health Organization (WHO) classification system was used. In
      addition to that, in moderately differentiated (MD) tumors small areas of solid
      growth were identified and the proportions of these out of the whole areas of
      tumor (in the predominant number of cases this being less than 5%) were later
      determined by morphometry, showing a good accordance with the subjective
      estimations. Differentiated tumors with small solid areas (MD + S tumors) implied
      a significantly worse prognosis compared to tumors without a solid component (P <
      0.001), which was also confirmed in a multivariate analysis. In the multivariate
      analysis MD+S differentiation had an independent prognostic impact, as strong as
      age, clinical stage and myometrial invasion. It is suggested that the occurrence
      of even a very small solid component is an ominous sign, the presence (or
      absence) of which might be an important parameter to take into consideration in
      the discrimination between high- and low-risk endometrial carcinomas.

PMID- 11578461
TI  - Influence of HSP27 and steroid receptor status on provera sensitivity, DNA-ploidy
      and survival of females with endometrial cancer.
AB  - Heat shock protein (HSP) 27, estradiol (ER), progesterone (PR), isocitric
      dehydrogenase and DNA-ploidy have been measured in 152 endometrial
      adenocarcinomas. These parameters have also been related to each other and to
      tumor grade and overall patient survival. HSP27 was assessed
      immunohistochemically and ploidy by FACS analysis, whilst biochemical methods
      were used for the other assays. HSP27 was significantly correlated with ER but
      not PR, grade or ploidy. Both ER and PR were related to tumor grade but not
      ploidy. Provera (2-14 days, mean 8) had no apparent effect on HSP27 staining but
      induced isocitric dehydrogenase in 70% of the tumors. Provera decreased ER (64%)
      and PR (70%) content in originally positive tumors. The presence of either HSP27,
      ER or PR in the pretreatment sample was significantly associated with provera
      induction of isocitric dehydrogenase activity; neither tumor grade nor ploidy
      predicted for induction of this enzyme. High levels of either HSP27, ER, PR or
      provera-induced isocitric dehydrogenase and diploid DNA were associated with good
      overall survival, whereas aneuploidy was linked with poor survival.

PMID- 11578462
TI  - Co-cultivation of ovarian carcinoma cells with dermal fibroblasts induces
      fibroblast expression of sex steroid receptor transcripts and protein.
AB  - We have previously reported that stromal fibroblasts of ovarian carcinoma
      specimens may express estrogen (ER) and progesterone receptors (PR) when the
      malignant epithelial cells do not, and even when the specimens have been obtained
      from such non-Mullerian structures as the omentum whose fibroblasts normally
      express neither ER nor PR. In an attempt to investigate whether our observations
      of the expression of ER and PR in fibroblasts surrounding metastatic invasive
      epithelial ovarian carcinoma cells might result from an interaction involving
      malignant epithelial cells and stromal fibroblasts, we co-cultivated in vitro BG1
      ovarian carcinoma cells with sex steroid receptor-negative dermal fibroblasts to
      determine whether carcinoma cells might induce the latter to express ER or PR
      protein and transcripts at levels detectable by standard immunocytochemical (ICC)
      and in situ hybridization (ISH) techniques. We report the in vitro induction of
      ER and PR transcripts and protein in previously steroid receptor-negative skin
      fibroblasts after co-cultivation with BG1 ovarian adenocarcinoma cells. Such
      observations suggest that a juxtacrine mechanism is responsible for the observed
      phenomenon, possibly involving ER- and PR-inducing factors (ER-IF and PR-IF).

PMID- 11578463
TI  - Detection of c-K-ras point mutation in ovarian cancer.
AB  - Point mutations of c-K-ras in ovarian cancer were detected by replacement of GGT
      of codon 12 by GAT, AGT, TGT and GTT, polymerase chain reaction, agarose gel
      electrophoresis and Southern blot hybridization with a digoxigenin detection
      system. The incidence of four-typed point mutations of c-K-ras oncogene in 37
      ovarian cancers was 35.1% (13/37) and the distributions were 32.4% (12/37), 2.7%
      (1/37), 0% and 0% of GGT to GAT, GGT to AGT, GGT to TGT, and GGT to GTT,
      respectively. The incidence of c-K-ras point mutations on codon 12 among 37
      patients with ovarian cancer was 35.5% (8/22) in those with serous
      cystadenocarcinomas and 28.6% (2/7) in those with mucinous cystadenocarcinomas. c
      K-ras point mutations on codon 12 were detected in 14.3% (1/7) of patients with
      stage I disease, 28.6% (2/7) with stage II disease, and in 43.5% (10/23) with
      stage III/IV disease, and there was a statistically significant increase in point
      mutations of c-K-ras oncogene with advancing clinical stage. The incidence of c-K
      ras point mutations on codon 12 among 33 patients who had a pelvic lymph node
      dissection was 52.4% (11/21) in those with pelvic lymph node metastases and 16.7%
      (2/12) in those without pelvic lymph node metastases, a statistically significant
      difference. Furthermore, point mutation of c-K-ras gene was found most frequently
      in patients with advanced stage disease, and in those with pelvic lymph node
      metastases. Activation of c-K-ras oncogene seems to be a major factor in ovarian
      carcinogenesis and tumor progression.

PMID- 11578464
TI  - Confirmation of the prognostic value of the ECPI-1 score (myometrial invasion,
      DNA-ploidy and mean shortest nuclear axis) in FIGO stage I endometrial cancer
      patients with long follow-up.
AB  - In FIGO stage I endometrial cancer patients, histologic type and grade are
      correlated with prognosis and used for therapeutic decision making. However,
      assessment of these histologic features is subjective, and the results are not
      always perfectly reproducible. Contrarily, previous studies have shown that DNA
      ploidy and morphometric features are highly reproducible and have a strong
      prognostic value in these cancers. Multivariate analysis has demonstrated that a
      combination of mean shortest nuclear axis (MSNA), DNA-ploidy and depth of
      myometrial invasion (the so-called ECPI-1 score) overshadowed the value of all
      other features investigated. The present study was set up to evaluate further and
      compare the prognostic power of the ECPI-1 score in 77 FIGO I patients with long
      follow-up (10-15 years). Grade (revised), invasion depth, MSNA and ploidy were
      all highly significant. However, the ECPI-1 score (with exactly the same
      threshold as in the previous study, 0.87) greatly exceeded the prognostic value
      of these single features. Only two (3%) of the 64 patients with ECPI-1 </=0.87
      died (at 14 and 62 months), in contrast to 11 (84.6%) of the 13 cases with ECPI
      1> 0.87 (10 died within 42 months) (P < 0.0001, Mantel-Cox value = 51.1). These
      results confirm the prognostic strength of the ECPI-1 score in stage I
      endometrial carcinoma.

PMID- 11578465
TI  - The role of the loop electrosurgical excision procedure in the diagnosis and
      management of early invasive cervical cancer.
AB  - The management of cervical intra-epithelial neoplasia (CIN) has evolved so that
      excisional techniques are now preferred over ablative procedures. This is in part
      due to a 1-3% rate of discovering unsuspected early invasive carcinomas that
      would not have been detected by ablative management of CIN. A review of our
      initial experience over 20 months with the loop electrosurgical excision
      procedure (LEEP) in treating CIN found seven out of 237 patients (3%) to have
      otherwise unsuspected invasive lesions. The management of three additional
      patients with suspected early invasive lesions has been facilitated by LEEP. The
      procedure has been found to produce excellent pathologic specimens and has
      virtually replaced traditional operative cervical conization in the management of
      both CIN and early invasive cervical cancer.

PMID- 11578466
TI  - In vivo evidence of increased malignant cell proliferation following surgery in
      ovarian cancer.
AB  - Flow cytometric evaluation of cellular DNA-ploidy and S-phase fraction was
      undertaken in serial post-operative peritoneal washings in 43 patients with
      histologically proven ovarian carcinoma, and 20 control patients. Five patients
      had FIGO stage I, two stage II and the remainder stage III/IV disease. Daily
      sampling of peritoneal fluid was performed commencing at day 0 (operation day)
      until the seventh post-operative day. Samples were analyzed fresh using a flow
      cytometer. Aneuploidy was detected in 168 (62.5%) of samples. Three patients had
      persistent diploidy throughout the study period, and were excluded from analysis.
      The mean aneuploid count rose from 24.7% [SEM (standard error of mean) = 4.6] on
      day 0 to 43.6% (SEM = 5.7) on day 4 (P < 0.008). The S-phase fraction for the
      aneuploid populations fell significantly (P < 0.02) from 4.9% (SEM = 1.2) on day
      0 to 2.2% (SEM = 0.8) on day 1, but subsequently continued to rise. Cytologic
      evaluation confirmed malignant cells in 79% of aneuploid samples. Three patients
      in the control population had similar patterns to malignant conditions, two of
      these patients having benign ovarian cysts and ascites. These findings show an
      increased proliferative activity of aneuploid malignant cells following surgical
      intervention, as detected in peritoneal lavage samples of patients with ovarian
      cancer.

PMID- 11578467
TI  - An anatomical study of inguinal lymph node topography and clinical implications
      for the surgical management of vulval cancer.
AB  - There is significant morbidity associated with inguinofemoral lymphadenectomy in
      the surgical treatment of vulval cancer, but surgical removal of all involved
      lymph nodes is integral to the treatment of the disease. In order to examine the
      feasibility of limiting the surgical dissection of the groin without compromising
      the removal of all lymph nodes, a study was undertaken to determine the exact
      location of the inguinal lymph nodes. Bilateral lower limb lymphangiograms from
      73 patients were analyzed to determine the location of the most laterally
      occurring lymph node relative to the anterior superior iliac spine (ASIS) and the
      most medial node relative to the pubic tubercle (PT). By conserving the lateral
      15% of fibro-fatty tissue overlying the right inguinal ligament and the lateral
      20% over the left inguinal ligament, there is statistically a greater than 99.8%
      chance of complete nodal clearance. The anatomical basis for a more conservative
      inguinofemoral dissection is provided that may decrease surgical morbidity
      without compromising survival.

PMID- 11578468
TI  - Platinum plus cyclophosphamide plus radiotherapy is superior to platinum alone in
      'high-risk' epithelial ovarian cancer (residual negative and either stage I or
      II, grade 3, or stage III, any grade).
AB  - Patients with epithelial ovarian cancer (EOC) referred to our institution are
      stratified into risk groups based on their stage, grade and presence of residual
      cancer, with a specific treatment policy for each group. One-hundred and thirty
      one patients with no visible residual tumor following primary surgery and either
      stage I, grade 3; stage II, grade 3; or stage III, any grade EOC were treated
      between November 1983 and the end of December 1991. Regimen A (cisplatin 75 mgm-2
      and cyclophosphamide 600 mgm-2 intravenously every 4 weeks for 6 cycles with
      abdominopelvic irradiation between cycles 3 and 4) was used until April 1989 and
      was then replaced with Regimen B (cisplatin 75 mgm-2 intravenously every 3 weeks
      for 6 cycles). The 5-year actuarial overall and failure-free survivals were 78%
      and 64% respectively. Multivariate analysis identified increasing stage and
      treatment with Regimen B as independent adverse prognostic factors for failure
      free survival. The importance of treatment regimen reached statistical
      significance for the stage I patients (P = 0.04) but not stage II (P = 0.11) or
      stage III (P = 0.79). It is possible to undertreat EOC as shown by the inferior
      results achieved with Regimen B (single agent cisplatin) compared to Regimen A
      (cisplatin-cyclophosphamide, irradiation). This effect of treatment regimen was
      particularly important for the lower-stage patients. Our postulate is that
      treatment resistant clones are less regularly present in lower-stage patients,
      and that a certain minimum amount of treatment is required to eliminate all the
      sensitive cancer.

PMID- 11578469
TI  - Extended radical hysterectomy in early-stage carcinoma of the uterine cervix:
      tailoring the radicality.
AB  - The question of whether surgical treatment in early-stage cervical cancer should
      be aggressive or restricted to less radical techniques is still controversial. To
      answer this question it was thought useful to investigate the correlation of
      parametrial lymph node metastases with extension and stage of disease. Two
      hundred and sixty-three consecutive primary radical surgical procedures were
      performed in our institute in clinical stage IB or stage IIA cervical cancer.
      Positive parametrial nodes were found in 6.9% of cases: 5% in stage IB (3% in the
      proximal part of the parametrium and 2% in the distal part, near the pelvic wall)
      and 16.3% in stage IIA (7% proximal and 9.3% distal) (P = 0.0193). During a
      median follow-up period of 92 months, disease recurred in 17.1% and 17.6% of
      cases, in negative and positive parametria, respectively. The 5-year overall and
      disease-free survival rates were 80.4% and 81.6% for patients with negative and
      positive parametria, respectively. From this experience it is concluded that the
      extent of radical hysterectomy should be related to the extent of the disease on
      the basis of modern knowledge of the pattern of spread. The principal key to
      prognosis remains pelvic and paracavoaortic nodal status.

PMID- 11578470
TI  - What have we achieved in ovarian cancer? A comparison of survivals and resources
      in two different periods.
AB  - In a geographically well-defined region in Denmark, survival and resource
      spending for strictly defined epithelial ovarian cancer patients treated during
      the periods 1973-1978 and 1981-1986 were compared. Almost all epithelial ovarian
      cancer patients diagnosed during the periods involved were identified; in both
      periods 206 patients were found. The number of patients was cross-checked with
      the Danish Cancer Registry. Treatment strategy was totally different in the two
      periods. In the first period debulking surgery was not routine and postoperative
      treatment consisted of pelvic irradiation and alkylating agents. In the second
      period the patients were treated according to national protocols prescribing
      debulking surgery, second-look laparotomy, and allocation to randomized trials.
      Advanced ovarian cancer patients were treated with combination chemotherapy with
      cisplatinum. Median survival was superior for the period 1981-1986, but long-term
      survival was similar in the two periods, 5-year survival being 27.5% for the
      period 1973-1978 and 26.9% for the period 1981-1986. The resources spent on
      ovarian cancer patients were calculated for the two periods, expressed as 'bed
      days' spent on ovarian cancer. An estimate of the price of the extra resources
      used was made; in the second period $1.18 million $US more were spent on ovarian
      cancer. The costs were correlated with survival and the cost per gained year of
      life was estimated as $36 493. In conclusion, the study shows that for all stages
      of ovarian cancer an improvement of median survival was found, but not of long
      term survival. The survival gain was associated with extra resource spending.

PMID- 11578471
TI  - Recurrent ovarian granulosa cell tumor: a case report of a dramatic response to
      Taxol.
AB  - A case is described of a granulosa cell tumor (GCT) of the ovary that recurred 2
      years after cessation of platin-based chemotherapy. In view of the extent and
      volume of the disease at recurrence, and because of the reported poor response
      rates to second-line chemotherapy, Taxol was given. There was a dramatic response
      and tumor shrinkage to single-agent therapy with Taxol.

PMID- 11578472
TI  - Neurotoxicity of cisplatin and taxol.
AB  - Since the discovery of the activity of cisplatin in ovarian cancer approximately
      15 years ago, there has been little progress in improving survival for patients
      with this disease. Thus there has been great enthusiasm in the gynecologic
      oncology community over the results of GOG111, the Gynecologic Oncology Group
      (GOG) study randomizing suboptimally debulked ovarian cancer patients to
      cisplatin with either cyclophosphamide or paclitaxel (TaxolR). To date, a median
      survival increase of 13 months has been seen in patients on the taxol-containing
      arm (ref. 1; W.P. McGuire, personal communication). Although a confirmatory study
      is about to be implemented by the European Organization for the Research and
      Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC),
      the GOG results are encouraging enough that the majority of ovarian cancer
      protocols developed over the next decade will probably incorporate some
      combination of cisplatin and taxol. Since neurotoxicity is now the dose-limiting
      toxicity of each of these agents, the potential for synergistic toxicity is of
      major concern, particularly with the tendency for recent protocols to investigate
      higher doses of both cisplatin and taxol than those used in the GOG study, which
      were 75 mg m-2 and 135 mg m-2 respectively. This paper will review the clinical
      manifestations and pathogenesis of the neurotoxicity of cisplatin and taxol as
      single agents, as well as in combination. The discussion will include several
      promising compounds which appear to prevent or diminish this sometimes severely
      disabling neurotoxicity.

PMID- 11578473
TI  - Predictive value of the combination of serum markers, CA125, CASA and TPS in
      ovarian cancer.
AB  - The serum markers CA125, CASA and TPS were compared, with particular reference to
      the clinical applications of these tumor markers in the management of patients
      with ovarian cancer (discrimination of benign and malignant disease; indicating
      prognosis; predicting preclinical recurrence), (i) Using recommended cut-off
      points, CASA (>/=4 U ml-1 and TPS (>/=80 U l-1 showed similar sensitivities in
      ovarian carcinoma (56% and 57% respectively), though these were lower than with
      CA125 (85% >/= 35 U ml-1). The combined use of CA125 with either CASA or TPS at
      higher cut-off points excluding benign disease (CA125> 345 U ml-1; CASA> 6 U ml
      1; TPS> 359 U l-1) improved the discrimination of ovarian cancer from benign
      adnexal masses (100% positive predictive value with 65% of ovarian cancers
      detected with CA125-CASA, 61% with CA125-TPS vs 46% with CA125 alone). The
      combined preoperative use of these markers may therefore assist the general
      gynecologist in avoiding potentially difficult oncologic surgery. (ii) TPS was
      the best preoperative indicator of prognosis, possibly due to its association
      with cell proliferation, while CASA was superior as a postoperative
      prechemotherapeutic prognostic indicator, possibly due to it being a more
      accurate indicator of residual disease than the other markers, or the surgeons'
      assessment. Similarly, CASA gave the best differentiation of patients with
      minimal residual disease (<1 cm) into those with a good or poor prognosis, (iii)
      CA125 and CASA each detected preclinical recurrence after surgery and adjuvant
      therapy in seven of 11 patients (mean lead times 4.6 and 3.1 months respectively)
      while TPS detected four of these patients (mean lead time 2.4 months). The
      combined use of CA125 with either assay led to the preclinical detection of eight
      of 11 patients, with the mean lead time increased to 5.3 months with the CA125
      CASA combination.

PMID- 11578474
TI  - Primary adenocarcinoma of the cervix. A clinicopathologic study of prognostic
      variables in 55 cases.
AB  - Fifty-five primary invasive adenocarcinomas of the cervix, presenting over a 20
      year period, were retrospectively studied with particular reference to clinical
      and pathologic prognostic indicators. Mean age at presentation was 54.5 years
      (range 27-91), with an age distribution showing two incidence peaks of equal size
      in the 31-35 and 61-65 groups, respectively. Twenty-four patients died of the
      disease and the remaining patients were followed up for a mean of 4.9 years
      (range 1-17). The results were analyzed using a Cox's proportional hazards
      survival model. The independent good prognostic indicators were early tumor stage
      (P < 0.001). and young patient age (P < 0.001) at presentation. The presence
      within the tumor of numerous intraepithelial lymphocytes and the concomitant
      occurrence of background in situ carcinoma were also good prognostic indicators,
      although these did not operate independently of stage and age. Histologic tumor
      subtype and grade of tumor differentiation were not significant prognostic
      factors. Treatment did not have a significant independent effect on survival. No
      definite conclusions could be drawn about the effect of oral contraceptives on
      the disease process.

PMID- 11578475
TI  - Expression of integrin adhesion molecules in normal ovary and epithelial ovarian
      tumors.
AB  - The metastatic potential of a solid tumor is dependent upon its ability to
      interact with the extracellular matrix. The integrin superfamily is a group of
      proteins that are fundamental in such interactions and play a major role in cell
      cell and cell-matrix adhesion. Localization of the integrin proteins was
      performed in normal ovary, primary epithelial ovarian tumors and metastatic tumor
      cells in ascitic samples. Expression of alpha1, alpha3, alpha6 and beta4 was
      observed on normal ovarian epithelium with variable expression of alpha5. Loss of
      alpha1 expression by malignant cells in the primary tumors was noted. beta4, a
      component of the laminin receptor which was strongly expressed by both normal
      ovary and solid tumor, was absent from the ascitic tumor cells in the majority of
      cases. There was an associated loss of alpha6 expression, indicating a deficiency
      of hemidesmosomes in the ascitic tumor cells. This alteration of integrin
      expression by metastatic malignant epithelial ovarian tumor cells may therefore
      represent one important mechanism by which metastatic disease occurs.

PMID- 11578476
TI  - Expression of the CD44 adhesion molecule in primary and metastatic gynecologic
      malignancies and their cell lines.
AB  - CD44 is a cell-surface molecule that has been shown to have several splicing
      isoforms. In various human tumors, such as primary colon and breast tumors, and
      their metastases, alterations of CD44 isoform expression have been reported. The
      present study was performed to investigate CD44 alternative transcript splicing
      in gynecologic malignancies. We performed reverse transcriptase polymerase chain
      reaction (RT-PCR) analysis of CD44 splice variant expression on mRNA transcripts
      from ovarian carcinomas (six primary and 15 metastatic tumors) from 21 patients
      and from cervical carcinomas (25 primary and two metastatic tumors) from 25
      patients. We also performed this analysis on five different ovarian carcinoma
      cell lines established from ascitic fluid and primary tumors, and two cervical
      carcinoma cell lines. We included eight normal female genital tissue specimens
      and one additional placenta specimen in our RT-PCR analysis for comparison with
      CD44 expression of carcinomas. The CD44H isoform was amplified in all of the
      specimens. None of eight normal tissue specimens, including myometrium and ovary,
      expressed CD44R1 transcripts. But the CD44R1 transcript was expressed in 2/6
      (33.3%) primary ovarian carcinomas and in 7/15 (46.6%) metastatic ovarian
      carcinomas. In cervical carcinoma, 13/25 (52.0%) primary tumors and 2/2 (100.0%)
      metastatic tumors expressed CD44R1. The CD44R1 transcript was expressed
      increasingly during ovarian and cervical tumor progression (P = 0.026 and P =
      0.002, respectively). In conclusion, the frequency of CD44R1 transcript
      expression increased during ovarian and cervical carcinoma progression, and
      analysis of CD44 splice variants may be useful in detecting primary and
      metastatic gynecologic malignancies.

PMID- 11578477
TI  - Small cell carcinoma of the cervix.
AB  - Small cell carcinoma of the cervix is an uncommon aggressive variety of cervical
      cancer. Between 1982 and 1993, eight cases of this disease were diagnosed at the
      Queensland Centre for Gynaecological Cancer among 1586 cervical cancers.
      Treatment results have been poor with one long-term survivor. Literature review
      suggests that aggressive chemotherapy combined with surgery and/or radiotherapy
      may improve survival.

PMID- 11578478
TI  - An immunohistochemical study of the incidence and significance of
      carcinoembryonic antigen in malignant endometrium.
AB  - In an immunohistochemical study of the presence of carcinoembryonic antigen (CEA)
      in endometrial carcinomas, it was found that CEA was detectable in 92 of 171
      neoplasms, an incidence of 53.8%. The antigen was unrelated to important
      prognostic variables, both clinical and histopathologic, and overall there was no
      difference in survival rates between CEA-positive and CEA-negative endometrial
      neoplasms during the 10-year follow-up period. CEA-negative carcinomas did,
      however, confer longer survival in certain subgroups of patients: those with
      adenocarcinomas arising from a hyperplastic endometrium, those with neoplasms of
      poor differentiation, and those who, in addition to surgery, received irradiation
      treatment. It is suggested that immunoperoxidase staining for CEA may provide an
      independent method for predicting radiosensitivity in endometrial carcinomas, and
      also may be indicative of prognosis within some forms of this malignancy.

PMID- 11578479
TI  - Characterization of human ovarian epithelial tumors (ex vivo) by proton magnetic
      resonance spectroscopy.
AB  - Proton magnetic resonance spectroscopy (1H MRS) offers an alternative
      investigational modality that will assist current pathologic techniques in the
      diagnosis of human ovarian epithelial tumors. Histologically normal human ovarian
      tissue (n = 12) was compared with ovarian benign fibromas (n = 3) and surface
      epithelial-stromal tumors (benign, n = 18; proliferating, n = 9; frankly
      malignant, n = 30) ex vivo by 1H MRS. The distinction between carcinomatous and
      benign or normal tissue (P<0.0001; Student's t-test) was made on one-dimensional
      (1-D) 1H MR spectra utilizing differences in resonance intensities of cellular
      lipid, creatine/phosphocreatine and lysine. The sensitivity and specificity of
      the test were 87% and 91%, respectively. Two-dimensional (2-D) MRS of
      carcinomatous biopsies showed multiple crosspeaks attributable to cell-surface
      fucosylation that correlated with tumor grade and loss of cellular
      differentiation. The multiple fucose crosspeaks were absent in spectra from
      normal ovary and benign tumors. The distinction between carcinomatous and normal
      or benign tissue based on MR-visible fucosylation gave a sensitivity and
      specificity of 88% and 97%, respectively. Proliferating tumors exhibited a range
      of cell-surface fucosylation patterns indicative of malignant potential.

PMID- 11578480
TI  - Detection of malignancy in endometrium by brush sampling in 1042 symptomatic
      patients.
AB  - Endometrial brush samples were taken from 1042 symptomatic hospital patients
      using Uterobrush(R), and the results were compared either to the histology of the
      endometrium obtained with dilatation and curettage (n = 313) or the patients'
      follow-up (n = 729). Only one cancer (100%) among patients </= 51 years of age (n
      = 677) was found by this method. Of the 12 cancers among patients> 51 years of
      age (n = 365), 11 (91.7%) were detected by Papanicolaou classes III-V. One cancer
      was missed, whereas no false positive results were found. The diagnostic accuracy
      in this group of patients varied from 92.3% to 97.8%, depending on the group
      (true positive vs true negative) to which the Papanicolaou class III was placed.
      We conclude that endometrial cytology obtained by brushing is useful for
      symptomatic patients of all age groups and gives an indication for further
      examination. If cytology is normal and bleeding continues in postmenopausal
      patients, curettage is indicated.

PMID- 11578481
TI  - Indium-111 labeled leukocytes in evaluation of active specific immunotherapy
      responses.
AB  - Active immunization of patients utilizing viral oncolysates (VO) has been studied
      in clinical trials. VO are extracts of cultured tumor cells that have been
      infected with certain types of viruses, particularly surface budding varieties.
      The objectives of the current studies were to examine the trafficking patterns of
      Indium (In)-111-labeled leukocytes or lymphocytes in two groups of patients with
      gynecologic malignancies to determine whether these cells migrate to sites of
      active immunization after VO. Eight patients with ovarian cancer received VO
      intraperitoneally followed by In-111-labeled leukocytes or lymphocytes (500
      &mgr;Ci) intravenously. In a separate trial, three patients with cervical cancer
      received In-111-labeled lymphocytes after they had been treated with VO
      administered by the intralymphatic route. Gamma camera imaging was performed to
      evaluate the distribution patterns of the labeled cells at several time intervals
      after injection. Results indicate that metastatic tumor sites exposed to VO
      therapy show significant uptake of In-111 cells. These sites of malignancies were
      confirmed by computerized tomography and ultrasound scans. In patients with
      ovarian cancer no uptake of the radiolabeled cells was observed in metastatic
      tumors of the liver and lymph nodes. In patients with cervical cancer, lymph node
      metastases exposed to intralymphatic VO therapy were visualized very well. Other
      known tumor sites not exposed to VO therapy showed no uptake of radioactivity.
      These findings confirm that VO induces immune responses. This diagnostic nuclear
      medicine technique may prove to be a useful method for following-up responses to
      immunotherapy.

PMID- 11578482
TI  - Endometrial hyperplasia and the risk of carcinoma.
AB  - Recent reports suggest that atypical endometrial hyperplasia diagnosed by biopsy
      or curettage is accompanied by a higher than expected risk of coexistent invasive
      cancer. In order to test this hypothesis we reviewed the pathology and clinical
      history of all patients at our institution who underwent hysterectomy for
      endometrial hyperplasia with or without cytologic atypia. We found 24 patients of
      45 with a preoperative diagnosis of hyperplasia with cytologic atypia, and 21
      with simple or complex hyperplasia without atypia. No cancers were found at
      surgery in the latter group nor were any significant historical differences found
      between the two groups. Of the patients with atypia, 12/24 (50%) had an
      endometrial carcinoma and nine patients (37.5%) were stage IB or greater. This is
      a significantly greater risk than previously reported in the literature.
      Endometrial hyperplasia with cytologic atypia may carry a higher risk of
      coexistent invasive endometrial carcinoma than previously believed. Methods to
      identify those patients at highest risk should be determined.

PMID- 11578483
TI  - An unusual endometrioid adenofibroma of the uterine cervix: a histologic and
      immunohistochemical study.
AB  - An unusual adenofibroma of the uterine cervix is reported. The cervix was bulkily
      enlarged but did not have a polypoid appearance. The neoplastic epithelium was in
      continuity with the covering epithelium of the cervix and consisted predominantly
      of endometrioid cells which proliferated to form numerous glandular structures of
      irregular size and shape. The glandular component resembled an endometrial
      hyperplasia, and was set in an abundant fibrous stroma which was moderately
      cellular and hyalinized. Both the epithelial and mesenchymal cells lacked
      cytologic atypia. Despite its benign appearance, the tumor occupied almost all
      the uterine cervix and extended into the upper vaginal wall. The epithelial cells
      showed diffuse positive staining for CA19-9 and were focally positive for
      carcinoembryonic antigen. The presence of dense periglandular fibrosis
      distinguished the present case from a minimal deviation adenocarcinoma of
      endometrioid type.

PMID- 11578484
TI  - Placental site trophoblastic tumor. Report of three cases and review of the
      literature.
AB  - Three cases of placental site trophoblast tumor (PSTT) are added to 74 cases in
      the English language literature. One case presented with an anorexic syndrome,
      the other two with amenorrhea and abnormal vaginal bleeding. The three patients,
      whose lesions were confined to the uterus, were treated by total hysterectomy and
      their follow-up has been uneventful. Review of the literature showed that 62
      patients with PSTT were alive and 15 had died, two as a complication of
      treatment. The diagnosis of PSTT may be difficult on a dilatation and currettage
      specimen. Metastases are a powerful indicator of adverse outcome. Prognosis, as
      assessed on pathologic criteria, is unreliable; however, a mitotic count of more
      than five mitoses per 10 high power fields is significant. Surgery is the
      mainstay of treatment. Hysterectomy is generally indicated, but young patients
      who wish to remain fertile may be treated by conservative surgery. In a few cases
      of progressive disease, chemotherapy has achieved remission, but generally
      chemotherapy and radiotherapy are ineffective. Long-term follow-up is essential
      as PSTT may progress after years of remission. Serum human chorionic
      gonadotrophin (hCG) levels are the best available marker of disease, but the
      disease may still progress even if hCG levels are not raised.

PMID- 11578485
TI  - Resection of bulky positive lymph nodes in patients with cervical carcinoma.
AB  - From January 1987 to April 1992, 34 patients had resection of bulky positive
      lymph nodes, detected either at the time of radical hysterectomy (n = 23) or by
      computed tomographic (CT) scan of the pelvis and abdomen prior to radiation
      therapy for more advanced cervical cancer (n = 11). Following nodal resection, 33
      patients received pelvic external beam radiation, 28 received pelvic and para
      aortic radiation, and 23 received four cycles of cisplatin chemotherapy. The
      median number of resected positive nodes was 4, with a range of 1-44. All
      macroscopic nodal metastases could be resected in each patient and morbidity was
      acceptably low. Positive nodes were confined to the pelvis in 17 patients,
      involved the common iliac group in nine patients, and involved the para-aortic
      area in eight patients. With a mean follow-up of 36 months, 23 patients (67.6%)
      were alive, of whom 20 were free of disease. For patients having a radical
      hysterectomy, actuarial 5-year survival was 80% for patients with disease
      involving pelvic and common iliac lymph nodes, and 48% for those with positive
      para-aortic nodes. Survival for patients with completely resected bulky pelvic
      and common iliac nodes was comparable to that for patients with micrometastases.
      This study suggests that every effort should be made to identify patients with
      cervical cancer who have bulky positive lymph node metastases, and to remove
      these nodes surgically prior to radiation therapy.

PMID- 11578486
TI  - Chemotherapy rapidly alternating with accelerated radiotherapy for advanced
      carcinoma of the uterine cervix.
AB  - The objective of this study was to determine the feasibility of treating patients
      with advanced cervical carcinoma using a regimen combining chemotherapy with
      intermittent hyperfractionated teletherapy. Eight patients with advanced cervical
      carcinoma were treated with bleomycin, ifosfamide and cisplatin, followed by a 5
      day course of hyperfractionated external radiation. Three such courses were given
      at 21-day intervals. Treatment was completed using standard brachytherapy. Seven
      of the eight patients were evaluable for response; all obtained a complete
      response. Two patients developed recurrence (one in the pelvis and one distant)
      and died of disease. One patient died of treatment complications. The remaining
      four remain alive and free of disease 9-42 months after treatment. The
      simultaneous use of chemotherapy and intermittent hyperfractionated teletherapy
      is a promising strategy for the treatment of cervical carcinoma, resulting in a
      high rate of complete response.

PMID- 11578487
TI  - Further evaluation of reproducibility and prognostic value of histologic typing
      and grading in FIGO stage I ovarian cancer patients without systemic locoregional
      adjuvant treatment.
AB  - In order to analyse the reproducibility and prognostic value of histologic typing
      and different methods of histologic grading, 102 hematoxylin and eosin stained
      slides of primary FIGO stage I ovarian cancers of the common epithelial types
      were evaluated. Patients were treated by surgery only. Histologic typing was done
      using the FIGO criteria and overall total agreement was 61%. Survival was not
      statistically significant (P-value range: 0.31-0.66). For grading, three
      different methods were used: (a) the 'intuitive' method; (b) the FIGO method; and
      (c) the so-called Pathology Research and Practice (PRP) method, which is based on
      invasion, architecture and nuclear atypia. The best intra- and interobserver
      results were obtained with the PRP criteria (interobserver agreement rate: 84.3%,
      varkappa 0.67; intraobserver agreement rate: 87.3%, K 0.76). Univariate survival
      analyses showed significant differences between grades for all methods and
      observers. Results of the PRP method were clearly better than for the FIGO method
      (PRP, Mantel-Cox range 6.70-24.52,P-value range 0.07 - < 0.0001; FIGO, Mantel-Cox
      range 5.31-6.77,P-value range 0.07-0.034). The 5-year survival per grade showed
      considerable variation within and between the observers, and was higher with
      higher grade. We conclude that the assessment of histologic type was reproducible
      but prognostically not significant in this set of FIGO stage I ovarian cancer
      patients. The intra- and interobserver reproducibility of the same grading method
      was fair to good, and showed highly significant results for survival from the PRP
      method. However, application of different grading methods could result in
      considerable prognostic variations for the 'same' grades.

PMID- 11578488
TI  - 5T4 oncofetal antigen expression in ovarian carcinoma.
AB  - 5T4 oncofetal antigen is defined by a monoclonal antibody raised against human
      placental trophoblast, and recognizes a 72 kD glycoprotein expressed in many
      different carcinomas but detected only at low levels in some normal epithelia.
      Analysis of the patterns of expression of 5T4 oncofetal antigen in colorectal
      carcinomas has indicated a significant association between the presence of the
      antigen in tumor cells and metastatic spread. The 5T4 antigen expression of 72
      epithelial ovarian carcinomas has been investigated by immunohistochemistry; 71%
      of the carcinomas demonstrated positive 5T4 immunoreactivity in adenocarcinoma
      cells and/or associated stromal tissue. In order to assess any relationship to
      prognosis, the 5T4 phenotypes were analyzed with respect to various
      clinicopathologic features of the tumors and the clinical outcome of the patients
      assessed by survival and disease-free interval. There was a significant
      correlation between 5T4 expression and more advanced stage of disease (FIGO
      stages III and IV) (P < 0.001) and with poorly differentiated tumors (P = 0.036)
      compared to well or moderately differentiated tumors. Patients with tumors
      expressing 5T4 were less likely to respond well to adjuvant therapy (P = 0.030)
      and had a significantly worse outlook in terms of survival (P = 0.033) and
      disease-free interval (P = 0.033). This significance was not demonstrated as
      acting independently of FIGO stage and tumor differentiation.

PMID- 11578489
TI  - An immunohistochemical study of estrogen and progesterone receptors in
      adenocarcinoma of the endometrium and in the adjacent mucosa.
AB  - The immunoperoxidase stain for estrogen and progesterone receptor content in
      endometrial adenocarcinoma was correlated with the grade and stage, level of
      myometrial invasion, age and survival of the patients. Anti-estrogen and anti
      progesteone receptor monoclonal antibodies were applied to paraffin-embedded
      tissue from hysterectomy specimens of 100 patients with adenocarcinoma of the
      endometrium. In 34 of the cases the receptors were studied in the endometrium
      adjacent to the tumor and compared to the nuclear receptor content in the
      carcinoma. There was a high inverse correlation between the estrogen receptor
      status and the grade of tumor (R = - 0.45, P = 0.006). The estrogen receptor
      measured in the endometrium near the tumor showed a negative correlation with the
      grade of the tumor (R = -0.42, P = 0.013). The estrogen, but not the
      progesterone, receptor content, was positively related to the age of the patient
      (P < 0.05). No significant correlation of the receptor status with the depth of
      myometrial invasion was found, despite the obvious interdependence between the
      grade and myometrial invasion. The progesterone receptor staining index appeared
      to be a distinct independent prognostic factor in endometrial cancer. The
      immunohistochemical analysis of the steroid hormone status in endometrial cancer
      therefore offers an alternative to the quantitative ligand-binding assay.

PMID- 11578490
TI  - c-erbB-3 proto-oncogene expression in uterine cervical carcinoma.
AB  - Over-expression of epidermal growth factor receptor (EGFR) and c-erbB-2, in
      uterine cervical carcinomas, is associated with a worsened prognosis. A third
      member of this proto-oncogene family, c-erbB-3, has now been identified and its
      over-expression has been described in a variety of carcinomas. In this
      immunohistochemical study we have shown that c-erbB-3 is widely expressed in
      cervical carcinomas, but we have found no association between its over-expression
      and lymph node status or clinical outcome. In a similar study examining the
      expression of EGFR and c-erbB-2 it was possible to demonstrate an association
      between over-expression and a worse prognosis. We conclude, therefore, that it is
      unlikely that demonstration of c-erbB-3 over-expression will be of any value as a
      prognostic indicator in carcinoma of the uterine cervix.

PMID- 11578491
TI  - Basement membrane patterns in borderline tumors of the ovary. An
      immunohistochemical study with antibodies to laminin and type IV collagen.
AB  - Using antibodies directed against the basement membrane (BM) components laminin
      and type IV collagen, basement membrane patterns were studied in borderline
      epithelial tumors of the ovary. To determine the potential use of BM
      immunohistochemistry in the histopathologic diagnosis of tumors of borderline
      category, BM patterns were compared with those in cystadenomas and
      cystadenocarcinomas. In cystadenomas, regular and intact BM were found at the
      interface between the epithelial cells of the cysts and the adjacent stroma.
      Cystadenocarcinomas displayed an irregular pattern, with areas of intact BM
      between tumor cells and stroma, as well as areas with irregular discontinuities.
      Tumors of borderline malignancy shared a continuous BM pattern with cystadenomas,
      However, 30% of the borderline malignant tumors contained small areas with BM
      interruptions resembling those of invasive carcinoma. From the results of this
      study we conclude that BM patterns in ovarian tumors of borderline malignancy are
      mostly similar to those of benign epithelial tumors. Focal defects possibly
      indicating early invasive growth, however, occur in 30% of the cases.

PMID- 11578492
TI  - Screening for ovarian cancer using serum CA125 and vaginal examination: report on
      2550 females.
AB  - This study was undertaken to assess the effectiveness of using serum CA125 and
      vaginal examination as a screening test for ovarian cancer in apparently healthy
      females. Two thousand five hundred and fifty healthy females aged 40 and over
      were recruited to participate in a screening study involving a questionnaire,
      serum CA125 measurement and vaginal examination. Females with either an elevated
      CA125 level or abnormal vaginal examination had a pelvic ultrasound performed as
      a secondary procedure. The positive predictive values of an elevated serum CA125
      level, and a combination of CA125 level measurement and vaginal examination for
      ovarian cancer, were 1/100 and 1/3, respectively. The specificities of serum
      CA125 levels, vaginal examination and both in combination were 96.1%, 98.5% and
      99.9%, respectively. In postmenopausal females the positive predictive values
      were improved with CA125 measurement alone, giving a positive predictive value of
      1/24. Seventeen females underwent operative procedure as a result of the
      screening-only one of these was for an ovarian cancer. The combination of serum
      CA125 measurement and vaginal examination is not an effective screening test in
      the general population, although in postmenopausal females it does achieve
      acceptable specificities and positive predictive values.

PMID- 11578493
TI  - Radical surgery after induction chemotherapy in locally advanced cervical cancer.
      A feasibility study.
AB  - In locally advanced cervical cancer, neoadjuvant chemotherapy has been shown to
      be effective for treatment of both the primary lesion and of metastatic lymph
      nodes. However, tumor necrosis and regression are often associated with dense
      fibrosis, which may complicate the surgical management. Forty-five patients with
      stage IB bulky-IIIB squamous cell carcinoma of the cervix underwent radical
      hysterectomy plus para-aortic and pelvic lymphadenectomy after one to three
      courses of different neoadjuvant cisplatin-based chemotherapeutic regimens. Mean
      operating time was 240 min. One major hemorrage was the only complication related
      to the para-aortic and pelvic node dissection. The parametrial dissection could
      be carried out in all patients. Intraoperative complications related to this part
      of the operation included two rectal and three urinary injuries repaired with no
      postoperative sequelae. In the specimens, residual parametrial infiltration was
      present in three out of 15 stage IIB-IIIB cases. The intraoperative complication
      rate was 13.3% and the gross postoperative complication rate was 4.4%.
      Postoperatively, only one case of ureteral fistula was recorded, yielding a rate
      of 2% (1/45). These data are not significantly different from those reported in
      the literature for radical surgery without neoadjuvant chemotherapy. In locally
      advanced cervical cancer, radical surgery after neoadjuvant chemotherapy is
      feasible without any undue increase in morbidity and mortality.

PMID- 11578494
TI  - Tamoxifen in patients with advanced epithelial ovarian cancer.
AB  - Tamoxifen was administered to 30 patients with persistent or recurrent epithelial
      ovarian cancer following initial plantinum-based chemotherapy. Two complete
      remissions (lasting 41 months and 12 months, respectively) were documented
      (6.6%), while 10 patients (33.3%) had stabilization of disease for a mean
      duration of 11.5 months. Tamoxifen was not associated with any significant
      toxicity and is a reasonable therapeutic option for patients with persistent or
      recurrent ovarian cancer, although it is only associated with modest activity.
      This paper reviews our experience with tamoxifen and summarizes the world
      literature.

PMID- 11578495
TI  - Periovulatory multifocal mesothelial proliferation: a possible association with
      malignant transformation.
AB  - This study was aimed at the identification of the site and characterization of
      the kinetics of tissue renewal during the repair of the ovarian surface
      epithelium (OSE) surrounding ovulation. Prepubescent C57BL female mice were
      induced hormonally either by intraperitoneal (ip) injection of pregnant mare
      serum gonadotropin (PMSG, 5 IU) +/- human chorionic gonadotropin (HCG, 5 IU) 46 h
      later, or subcutaneous (sc) diethylsilbesterol (DES) 0.1 mg or 1.0 mg in 0.5 ml
      corn oil, in addition to saline-injected controls. The animals were killed after
      various time intervals. Autoradiography was carried out on formaldehyde-fixed
      paraffin sections of genital organs with subsequent hematoxylin & eosin staining.
      The preparations were examined for nuclear [3H]thymidine incorporation (0.5
      &mgr;Ci injected 1 h before killing) in the OSE, as well as the surrounding and
      more distal mesothelium. Surprisingly, a significant proliferative response was
      observed in the extra-ovarian mesothelium surrounding the uterine horns, tubes
      and nearby peritoneum, while the OSE proliferation rate was less than half of it.
      In contrast to the common notion, it seems that the expansion and repair of the
      OSE, associated with ovulation, is contributed mainly by its extra-ovarian
      mesothelial continuum. This observation may provide additional support to the
      multifocal theory suggested in the pathogenesis of ovarian cancer. Therefore, any
      search for cellular or molecular events related to malignant transformation
      should include the proximal and distal mesothelium in addition to the OSE.

PMID- 11578496
TI  - Is there an association between long-term tamoxifen treatment and the development
      of carcinosarcoma (malignant mixed Mullerian tumor) of the uterus?
AB  - A cluster of five patients with endometrial carcinosarcoma (malignant mixed
      Mullerian tumor) occurred at our center during 1993; four of these had been
      prescribed long-term tamoxifen for breast carcinoma. Searching the archives for
      the 9-year period 1983-1992 revealed two further cases of uterine carcinosarcoma
      occurring in patients prescribed tamoxifen, from a total of 16 cases of this
      tumor. Five of the six patients diagnosed with carcinosarcoma who had been taking
      tamoxifen had been maintained on the drug for at least 6 years, while the other
      had a 3-year history of tamoxifen therapy. From these data we raise the question
      of an association between long-term tamoxifen treatment and development of
      endometrial carcinosarcoma, following the dramatic increase in the prescribing of
      this drug after 1984.

PMID- 11578497
TI  - Ovarian hepatoid carcinoma without staining for alpha-fetoprotein in the primary
      site.
AB  - An ovarian hepatoid carcinoma associated with minimal alpha-fetoprotein (AFP)
      production is described. The tumor involved both ovaries, and had metastasized to
      the omentum, uterus and retroperitoneal lymph nodes. The neoplastic cells were
      arranged in sheets, had abundant eosinophilic cytoplasm, central nuclei and
      distinct cellular borders. Despite the morphologic similarity to the histology of
      a hepatocellular carcinoma, elevation of the serum AFP level was minimal, at 74.0
      ng ml-1 (normal range: under 20 ng ml-1), and the value normalized after surgery
      and subsequent chemotherapy. An immunohistochemical technique revealed focal
      staining for albumin in the tumor tissue and AFP in the uterine metastasis. Since
      the primary tumor itself did not stain for AFP, it is suggested that there may be
      hepatoid ovarian carcinomas without AFP production, a situation found in some
      hepatocellular carcinomas.

PMID- 11578498
TI  - Viral testing for genital human papillomavirus infections: recent progress and
      clinical potentials.
AB  - Recent technologic advances indicate the potential role and applications of human
      papillomavirus (HPV) DNA testing in the routine screening for cervical neoplasia,
      diagnostic triage of females with inconclusive cervical cytologic smears, and
      quality control of cytologic and pathologic practices.

PMID- 11578499
TI  - Cancer of the cervix, FIGO stages IB and IIA: patterns of local growth and
      paracervical extension.
AB  - The relationship between patterns of local growth and paracervical extension of
      cervical cancer was evaluated in operative specimens of 230 patients with
      squamous cell carcinoma FIGO stage IB and IIA who were primarily treated, between
      January 1989 and December 1993, by abdominal radical hysterectomy with pelvic
      lymphadenectomy. Twelve cervical giant sections, each representing an area of 30
      degrees, including the corresponding paracervical tissues (lateral parametria,
      vesicocervical ligaments, and uterosacral ligaments), were made parallel to the
      cervical canal, and serial horizontal step sections at 3 &mgr;m were cut.
      Cervical carcinoma spread endocervically equally in all directions; higher
      frequencies were observed in the front and back cervical quadrants (about 28%)
      than in the lateral ones (about 22%) (P = NS). The corresponding tumor extension
      beyond the cervix was into the vesicocervical ligaments (anterior parametria) and
      the vesicocervical septum in about 23% of cases, into the uterosacral ligaments
      (posterior parametria) and the rectovaginal septum in about 15% of cases, and
      into right and left lateral parametria in about 28% and 34% cases, respectively.
      Paracervical extension (26%) was significantly related to the maximum depth of
      stromal invasion (chi2 = 19.11; P < 0.01), minimum thickness of uninvolved
      fibromuscular cervical stroma (chi2 = 32.34; P < 0.01), lymphatic invasion (chi2
      = 17.91; P < 0.01), pelvic lymph node metastases, (chi2 = 48.37; P < 0.01) and
      tumor size (chi2 = 26.38; P < 0.01). Furthermore, involvement of anterior and
      posterior paracervical tissues was related to high percentages of the minimum
      thickness of unaffected cervical stroma in the corresponding front (92%) and back
      (88%) quadrants, whereas these percentages were much lower (30%) in lateral
      cervical quadrants with carcinomatous extension to lateral parametria. These
      patterns of growth suggest that surgery is only radical with respect to lateral
      parametria in the treatment of cervical cancer.

PMID- 11578500
TI  - Continuous intra-arterial cisplatin combined with radiotherapy in locally
      advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group pilot
      study.
AB  - The high local failure rate in patients with locally advanced carcinoma of the
      cervix treated with standard radiation has spurred interest in
      radiosensitization. Cisplatin is the most active single chemotherapeutic agent in
      squamous carcinoma of the cervix, and is considered to be a radiosensitizer.
      Based on a previous single-institution study looking at continuous low-dose intra
      arterial cisplatin given throughout planned radiation therapy in patients with
      advanced carcinoma of the cervix, the Gynecologic Oncology Group initiated a
      limited access pilot study to assess the feasibility of this treatment method for
      a group-wide study. Patients with locally advanced squamous carcinoma of the
      cervix and surgically documented negative periaortic lymph nodes were eligible
      for the study. During surgical staging, the catheters of a totally implantable
      pump were placed in the internal iliac arteries. The pump was filled with
      cisplatin which was delivered at 4.5-6.5 mg day-1 continuously throughout both
      external radiation and brachytherapy. Drug distribution through the catheters was
      determined using radiolabelled macro-aggregated albumin particles. Three of nine
      evaluable patients were free of disease at follow-up. Drug distribution was less
      than optimal through 4.6% of the pump catheters. Five patients had premature
      discontinuation of the cisplatin for various reasons. These problems resulted in
      low accrual and subsequent closure of the study. This treatment method is not
      feasible for a phase III evaluation on a group-wide basis.

PMID- 11578501
TI  - Implications of human papillomavirus type for survival in cervical squamous cell
      carcinoma.
AB  - In a Swedish series of 107 invasive squamous carcinomas of the cervix, DNA
      extraction from paraffin-embedded material was successful in 97 cases. The
      prevalence of human papillomavirus (HPV) in this material was 86.6%, as
      determined by polymerase chain reaction (PCR) using both consensus and type
      specific primers. HPV type 16 was most common (42.3%; other types were 31
      (12.3%), 18 (9.3%) and 33 (10.3%). Seventeen cases (17.3%) were positive for the
      consensus primers only and were regarded as HPV of unknown type. There was no
      significant difference in corrected survival between patients with HPV-positive
      or -negative tumors. In the HPV-positive group, patients with tumors containing
      HPV 33 or HPV 18 had a significantly poorer prognosis than patients with tumors
      containing other types of HPV DNA (relative hazard 3.18, 95% confidence interval
      1.37-7.39, P = 0.007), implying a prognostic significance of HPV type.

PMID- 11578502
TI  - Intestinal obstruction in patients with advanced ovarian cancer.
AB  - A retrospective analysis of the management of intestinal obstruction in 31
      patients with advanced ovarian carcinoma is described. Between 1981 and 1992 31
      patients developed intestinal obstruction after their initial treatment. Nineteen
      patients underwent surgery, while the remaining 12 were treated conservatively.
      Careful evaluation with contrast studies of both the small intestine and colon is
      recommended to improve the prediction of site(s) of obstruction, and may reduce
      the number of unsuccessful operative procedures. Fifteen of the surgically
      treated patients survived for a period of 60 days or more. The majority, 13, were
      discharged to their homes after an average hospital stay of 24 days. Major
      postoperative complications occurred in three of the 19 patients. There was no
      surgical-related mortality. Two patients died within 30 days postoperatively
      (urosepsis and advanced tumor). While the median survival in the 19 surgical
      treated patients was 109 days (range 15-775), the conservatively treated 12
      patients survived for a mean of 37 days (range 6-260). Surgical management of
      intestinal obstruction in selected cases is feasible and improves quality of life
      substantially.

PMID- 11578503
TI  - Phase II study of prolonged oral etoposide in refractory ovarian cancer.
AB  - A phase II study of prolonged oral etoposide at 50 mg m-2 was performed in
      patients with refractory ovarian cancer. A dose schedule algorithm was used to
      generate a calendar with the number of capsules to be administered each day and
      the date of blood tests. Fourteen of 15 patients were evaluable for response.
      Among the evaluable patients, 12 (86%) had poorly differentiated tumors, 13 (93%)
      had primary or secondary platin-resistant tumors, and 12 (86%) had progressed on
      a prior taxoid therapy. The median number of prior regimens was four (1-7).
      Despite the use of a 50-mg capsule of etoposide, the algorithm permitted the
      delivery of a median of 94% (89-107.5%) of the ideal calculated dose. The dose
      limiting toxicity was myelosuppression with a grade 3 or 4 neutropenia in two
      thirds of the patients. There were no deaths on the study and no significant
      neurologic or cardiovascular toxicity noted. There were no objective responses.
      The median survival of evaluable patients was 8.1 (95% CI 5.6-13.2) months.

PMID- 11578504
TI  - The significance of differences in prognostic value of quantitative pathologic
      features in FIGO stage III and IV serous adenocarcinoma of the ovary between a
      group of Danish patients and other groups.
AB  - Previous studies have shown DNA cytometric, morphometric and stereologic features
      to be strong prognosticators in advanced ovarian cancer. However, in one Danish
      study a new stereologic parameter, the volume-weighted mean nuclear volume (
      nuv), was not of prognostic significance. In that study, sampling was performed
      in the whole tumor section, contrary to that in other studies where measurements
      were performed in the worst differentiated area (the measurement area). The aim
      of the present investigation was, therefore, to confirm or reject the hypothesis
      that random estimates of nuclear {ovbar|nu}v over the whole tumor, rather than in
      the measurement area, are the cause for the lack of prognostic value in the
      Danish patients. Additionally, the mitotic activity index (MAI), volume
      percentage of epithelium (VPE), mean nuclear area (MNA) and standard deviation of
      the nuclear area (SDNA), which have proved to be of strong prognostic
      significance in advanced ovarian cancer, were assessed in the measurement area.
      The MAI, VPE, MNA, SDNA and nuclear {ovbar|nu}v were well reproducible, but
      prognostically not significant. This study thus excludes differences in
      microscopic sampling as an explanation for the contrasting findings in the Danish
      study and other ones. Possible remaining explanations are: (i) differences in
      sampling at the macroscopic level; (ii) fixation differences; (iii) patient
      selection bias; and (iv) geographic differences in the degree of malignancy of
      advanced ovarian cancer in Denmark and the Netherlands. As to the latter, in
      comparison with two Dutch studies the Danish ovarian cancers in this series had
      residual disease <2 cm (33% vs 50%) less often, were less often well
      differentiated (4% vs 19%), and less often had favorable morphometric
      characteristics (6% vs 15%). Further studies are required to analyze whether
      other Danish patient groups with advanced ovarian cancers differ from the Dutch.

PMID- 11578505
TI  - Intraperitoneal 5-fluorouracil for pseudomyxoma peritoneii.
AB  - Pseudomyxoma peritoneii has an indolent course but a 5-year survival rate of 40
      45%. The role for postoperative intraperitoneal chemotherapy is unclear. Nine
      patients with pseudomyxoma arising from mucinous neoplasms of the ovary and
      intestinal tract received a total of 89 courses of intraperitoneal 5-fluorouracil
      (IP5FU). Each course consisted of eight 4-h exchanges of 1 g of 5FU in 2 l of
      1.5% Inpersol(R). Median follow-up after diagnosis was 30 months (range 6-74).
      All patients were evaluable for toxicity and response. There was one treatment
      related death due to renal failure and sepsis. Three patients developed disease
      progression prior to scheduled second-look laparotomy. At second-look laparotomy
      two patients demonstrated pathologic complete responses, one had stable disease
      and one had progression of disease. One patient remained clinically free of
      progression after refusing second-look laparotomy. The projected 5-year survival
      by Kaplan-Meier estimate was 87% for patients treated with IP5FU compared to a
      52% 5-year survival seen in a series of 11 patients treated prior to the use of
      IP5FU (P = 0.12). This preliminary analysis suggests that IPFU in the described
      schedule fails to improve survival statistically compared to previously used
      regimens for patients with pseudomyxoma peritoneii.

PMID- 11578506
TI  - Lack of granzyme expression in T lymphocytes indicates poor cytotoxic T
      lymphocyte activation in human papillomavirus-associated cervical carcinomas.
AB  - Changes in major histocompatibility complex (MHC) class I expression in
      neoplastic cells are frequently observed in human papillomavirus type 16 (HPV16)
      associated cervical carcinomas. In order to investigate whether this affects
      cytotoxic T-cell (CTL) activation, 20 HPV16-positive cervical carcinomas with
      variable MHC expression were analyzed immunohistochemically for the expression of
      granzyme B and interleukin-2 receptor (IL-2R). The results revealed that most
      carcinomas show strong CD3+ T-lymphocyte infiltrates. In nine of these cases CD8+
      cells outnumbered the CD4+ cells, whereas in the remaining cases equal amounts of
      CD4+ and CD8+ cells were found. Double staining revealed that CD3+ granzyme B+
      cells were not detected in 19 out of 20 cervical lesions, whereas in one
      carcinoma an occasional cluster of granzyme B+ T cells was observed. Positive
      controls, including genital warts and renal allograft rejections, showed granzyme
      B+ T cells. In agreement with this observation was the extremely low frequency of
      IL-2R+ T cells in the carcinomas tested, while warts contained IL-2R+
      lymphocytes. The data indicate that cytotoxic (CD8+) T cells in cervical
      carcinomas are not activated, as demonstrated by the lack of granzyme B and IL-2R
      expression in the T cells.

PMID- 11578507
TI  - Long-term follow-up of patients with advanced ovarian cancers treated with
      intermittent administration of combination chemotherapy with cisplatin,
      doxorubicin and cyclophosphamide.
AB  - Despite high primary response rates with cisplatin-based combination
      chemotherapy, the overall survival rate for advanced ovarian cancers remains
      dismal. We designed a new systematic treatment approach with a combination
      chemotherapy consisting of cisplatin, doxorubicin and cyclophosphamide (cyclic
      PAC chemotherapy), with the aim of improving survival rates with minimal
      disturbance of quality of life. Cyclic PAC chemotherapy is a three-step
      chemotherapy with three courses of the PAC regimen in each step. A total of nine
      courses with a 3-month drug-free period between each step were administered over
      a 15-month period to patients with clinical stage IC-IV ovarian cancer who had
      undergone cytoreductive surgery. Forty-eight patients with stage IC-IV disease
      (34 patients with stage III and IV disease) were treated with cyclic PAC
      chemotherapy. Thirty-four patients with stage IC-IV disease (23 patients with
      stage III and IV disease) were treated by a brief course of PAC chemotherapy.
      Long-term survival and toxicity were evaluated for both treatment groups. Cyclic
      PAC chemotherapy improved the overall outcome of patients (66.6% 3-year and 56.5%
      5-year survival rates) compared to brief PAC (41.2% 3-year and 23.5% 5-year
      survival rates) (P < 0.01). The outcome of patients with stage III-IV ovarian
      cancer of the cyclic PAC group (52.6% 3-year and 37.2% 5-year survival rates) was
      also superior to that of the brief PAC group (21.7% 3-year and 8.7% 5-year
      survival rates). Generally, the treatment was well tolerated. The toxicity was
      similar in both groups, although myelosuppresion and neurotoxicity were rather
      prominent in the cyclic PAC group. Cyclic PAC chemotherapy may lead to improved
      survival in advanced ovarian cancer, and merits further investigation in a
      randomized study.

PMID- 11578508
TI  - Referral patterns for suspected ovarian cancer: a survey of practicing
      gynecologists.
AB  - We evaluated referral patterns for the initial surgery in patients with suspected
      ovarian cancer and factors associated with that referral. Through a mailed survey
      we asked gynecologists: (i) to rate the importance of characteristics of the
      patient, the mass, the surgeon and the hospital on to their decision to operate
      on or to refer to a gynecologic oncologist a patient with a pelvic mass; (ii) to
      indicate whether they would operate on or refer five hypothetical patients with
      masses of increasing complexity; (iii) to estimate on what proportion of patients
      with suspected ovarian cancer in their practice they currently operate; and (iv)
      to estimate the residual tumor volume when they perform surgery for ovarian
      cancer. Gynecologists seeing fewer patients with suspected ovarian cancers, in a
      teaching vs community hospital, in full-time university vs private practice and
      working in specific geographical areas, referred more to an oncologist for the
      primary surgery. Not significant were the gender of the surgeon, number of years
      in practice and distance to a regional cancer center. A high probability of
      cancer and characteristics of the surgeon affected referral patterns.

PMID- 11578509
TI  - Lack of effect from mitomycin c plus 5-fluorouracil in platin-resistant ovarian
      cancer: a phase II study.
AB  - Sixteen patients with advanced ovarian cancer were included in a phase II study
      with mitomycin c (MMC) plus 5-fluorouracil (5-FU). All patients had previously
      received platin-based combination therapy, but were resistant to this treatment.
      A MMC 10 mg m-2 intravenous (iv) bolus was given on day 1 every 6 weeks, and 5-FU
      1000 mg m-2 was given iv on days 1-3 every 3 weeks, as a continuous infusion over
      72 h. Fifteen patients were evaluable for response. There were no responders,
      neither partial nor complete. The median survival was 6 months. The toxicity was
      primarily bone marrow suppression. The treatment was generally well tolerated. No
      patients had grade 4 toxicity and only five had grade 3 hematologic toxicity. In
      conclusion, we find the present regimen to be ineffective in the treatment of
      platin-resistant ovarian cancer.

PMID- 11578510
TI  - A longitudinal study of screening for endometrial cancer by endometrial biopsy in
      diabetic females.
AB  - Diabetics are at high risk of developing endometrial cancer; the relative risk of
      endometrial cancer in diabetics is fourfold in comparison to non-diabetic
      controls. The purpose of this longitudinal study was to evaluate the
      effectiveness of screening asymptomatic diabetic females in terms of the
      premalignant and malignant endometrial findings, and to try to determine the
      optimal screening interval. In 1980-1981, a group of 462 diabetic females was
      identified and registered. One half of them (237) was invited to be screened.
      Endometrial samples were taken by using Vabra aspiration. The results of this
      first randomized screening in 1980-1981 have been published elsewhere. At that
      time 124 females participated. The remaining 225 females acted as an unscreened
      control group. Eight years later (1988-1989), both groups were invited to be
      screened. The Pistolet aspiration method was used. At this stage, group 1
      (screened in 1980-1981) consisted of 78 females, and group 2 (not screened in
      1980-1981) consisted of 148 females. In 85% (193/226) of the females, the uterine
      cavity was reached with the Pistolet instrument; 96% of the females found the
      pain acceptable. In the group screened twice (group 1), no pathologic lesions of
      the endometrium were found in the second screening. In the group screened for the
      first time (group 2), one female had endometrial adenocarcinoma (0.8%), one had
      complex hyperplasia without atypia (0.8%) and four had endometrial polyps (3.3%).
      In 165 cases of 193, both a cytologic and a histologic specimen were available.
      In 130 cases (79%) the cytology was of class I, including the one endometrial
      adenocarcinoma. In three cases (2%) it was of class II and in one case (1%) of
      class III. Endometrial biopsy by Pistolet aspiration was a method highly
      acceptable by the patients for examining the endometrium. However, cytologic
      examination was not able to show the existing endometrial adenocarcinoma. One
      endometrial sampling of asymptomatic diabetic females during early menopause
      could detect the bulk of the occult, slowly progressing lesions of the
      endometrium. Such screeening might be most efficient in terms of cost-benefit
      ratio.

PMID- 11578511
TI  - Paraneoplastic cerebellar degeneration in a patient with chemotherapy-responsive
      ovarian cancer.
AB  - A 54-year-old female with small volume residual stage III ovarian cancer had
      received two courses of carboplatin chemotherapy with obvious response, when she
      developed rapidly progressive neurological symptoms. Over a period of 48 h, an
      incapacitating syndrome of ataxia, nystagmus and dysarthria evolved. Central
      nervous system metastases were excluded by computed tomography scanning and
      cerebrospinal fluid cytology. Anti-Purkinje cell antibodies ('anti-Yo') detected
      in the serum confirmed the diagnosis of paraneoplastic cerebellar degeneration.
      Isolated reports have suggested that the clinical course of this condition can be
      ameliorated with high dose steroids and plasmapheresis. However, in this case the
      very early introduction of both these did not bring about any improvement in the
      patient's symptoms. She remained severely incapacitated and unable to care for
      herself for the remaining 15 months of her life. The patient died of progressive
      ovarian cancer that had become clinically evident 10 months after the onset of
      neurological symptoms. This case illustrates many of the classical features of
      this rare condition, and the world literature is reviewed.

PMID- 11578512
TI  - Development and in vitro characterization of a GM-CSF secreting human ovarian
      carcinoma tumor vaccine.
AB  - A human ovarian carcinoma cell line (UCI-107) was genetically engineered to
      secrete the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF),
      by retroviral medicated gene transduction. This line was transduced with the LXSN
      retroviral vector containing the human GM-CSF gene and the neomycin resistance
      selection marker. Numerous GM-CSF secreting clones were randomly isolated and one
      clone, termed UCI-107M GM-CSF-MPS, extensively characterized. This clone was
      shown to constitutively secrete high levels of GM-CSF (ie 420-585 pg ml-1 105
      cells-1 48 h-1 for over 35 passages and 6 months of study. Like the parental cell
      line UCI-107, UCI-107M GM-CSF-MPS cells expressed MHC class I and Her2/Neu
      surface antigens but did not express detectable MHC class II, ICAM-1 or CA-125.
      No change in the expression of these surface proteins was noted between the
      parental cells and this GM-CSF secreting clone. The morphology of UCI-107M GM-CSF
      MPS did not differ from that of the parental or LXSN vector control cells;
      however, parental cells had a slightly faster growth rate than the transductants.
      UCI-107M GM-CSF-MPS was sensitive to gamma irradiation, since as little as 2500
      rads killed the cells within 10 days of irradiation. However, even after higher
      doses of irradiation (ie 10000 rads), GM-CSF secretion continued in vitro until
      about day 8. Interestingly, irradiation induced up-regulation of the surface
      antigens previously expressed, and they remained up-regulated for as long as the
      cells remained viable. The potential use of these GM-CSF secreting ovarian
      carcinoma cells as vaccines for women with advanced ovarian cancer will be
      discussed.

PMID- 11578513
TI  - ErbB-2, a c-erbB-2-coded protein, is expressed in metastatic cells of
      adenocarcinoma of endometrium, cervix and ovaries.
AB  - Ten cases of gynecologic malignancies, including three endometrial, two ovarian
      and four cervical carcinomas, were studied for the expression of a 185 kDa
      protein (ErbB-2), coded by a proto-oncogene, c-erbB-2, in primary lesions as well
      as in metastatic lesions. Positive immunoreactivity was observed in all primary
      adenocarcinomas but not from squamous cell carcinomas. Many adenocarcinoma cells
      in distant metastatic sites or in tertiary lymph nodes were strongly stained for
      ErbB-2. These metastatic cells also showed an expression of proliferating cell
      nuclear antigen (PCNA). Detection of ErbB-2 mRNA by a reverse-transcription
      polymerase chain reaction showed that the transcription occurred exclusively in
      adenocarcinomas. To our knowledge, this is the first report demonstrating ErbB-2
      expression in distant metastatic lesions of gynecologic cancers.

PMID- 11578514
TI  - Surgery and prognosis in stage III epithelial ovarian cancer.
AB  - The results of this retrospective case study indicate that a composite of tumor
      grade, pattern of spread and substage at the time of opening affects the outcome
      most in the treatment of stage III epithelial tumors of the ovary. The poorest
      prognosis was associated with grade 3 histology, a pattern of spread requiring
      extensive and often difficult surgery for removal and a high substage. The best
      prognosis was usually associated with grade 1, with either very easily removed,
      isolated spread or low substage. The extent of tumor defined the degree of
      primary cytoreduction possible. If the tumor was minimally extensive, primary
      cytoreduction results were excellent. The same conclusions were reached in the
      case of secondary cytoreduction at the time of second-look procedure. There was
      no statistically significant difference (z = 1.481, P = 0.069) in 5-year survival
      between patients with microscopic only disease (59%) at second-look, and patients
      with gross disease not cytoreduced (36%).

PMID- 11578515
TI  - Squamous endometrial neoplasia-are Fluhmann's postulates still relevant?
AB  - A review of squamous neoplasia of the endometrium (in situ and/or invasive) with
      or without coexistent similar disease of the cervix, revealed four anatomical
      variants in 22 patients. The patterns were: Group (i), endometrial squamous
      neoplasia only; Group (ii), discontiguous endometrial and cervical squamous
      neoplasia; Group (iii), possibly discontiguous endometrial and squamous
      neoplasia; and Group (iv), contiguous endometrial and squamous disease. The
      details of the histology, management and outcome are discussed, the latter being
      much poorer for the fourth group. The criteria for diagnosing squamous neoplasia
      involving the endometrium are re-examined and a recommendation for these criteria
      is suggested.

PMID- 11578516
TI  - The LonStenn-a new cervical sampling device.
AB  - A new cervical sampling device, the 'LonStenn' was evaluated against devices in
      common use: the Cervex Brush, and the CytoBrush plus Ayres Spatula, by comparing
      the number of cells removed from the cervix and the number released from the
      device onto a glass slide. One hundred and eighty patients were studied. Ninety
      patients had Papanicolaou (Pap) smears, and at the same examination, colposcopy
      and biopsies, with 30 patients being allocated to each of the three sampling
      methods. After the plating of the Pap smear, the 'head' of the device was cut off
      and placed in a vial of Tyrode saline solution and vortexed. The residual cells
      remaining in the saline solution were counted in a Kova Slide Chamber. This
      allowed assessment of one possible cause of false negatives (ie, cell
      entrapment). A control group of 90 patients, with 30 allocated to each device,
      had Pap smears taken which were not plated out: the head of the device was
      removed and again placed in Tyrode saline solution. The cells harvested from the
      cervix were counted by the same method as before. The subtraction of the cells
      from the plated-out group from the control (nonplated out) group gave an
      indication of the number of cells delivered to the slide for cytological
      evaluation. The LonStenn is shown to be more efficient in its quantitative
      delivery of representative harvested cells from the cervix to a glass slide for
      cytological analysis. Qualitative assessment of smears prepared from this device
      suggested an improvement, as indicated by less blood staining. This should also
      ultimately be reflected by a decrease in false negatives in the laboratory.

PMID- 11578517
TI  - Pure malignant immature teratoma of the ovary: the role of chemotherapy and
      second-look surgery.
AB  - Fifteen patients with pure malignant immature teratoma of the ovary were treated
      at the Institut Gustave Roussy over a 17-year period. Chemotherapy was delivered
      as primary postoperative therapy in 11 patients. Four other patients received
      chemotherapy as part of their salvage treatment for recurrent disease. A second
      look laparotomy was performed in eight patients. Histological findings were: no
      tumor in three patients, mature teratoma in four patients, and immature grade 1
      teratoma in one patient. The latter five patients had persistent radiologic
      abnormalities at the end of chemotherapy. Twelve patients remain free of disease
      24-228 months from initiation of chemotherapy. Two children were delivered from
      the two patients who attempted pregnancy. All three patients who died of
      progressive disease had a grade 3 immature teratoma. We conclude that the
      treatment of pure immature teratoma of the ovary should include primary
      conservative surgery and cisplatin-based chemotherapy. Second-look surgery is
      mandatory in patients with persistant radiologic abnormalities at the completion
      of chemotherapy.

PMID- 11578518
TI  - Immunocompetent for immunotherapy? A study of the immunocompetence of cervical
      cancer patients.
AB  - Sixty-five patients with cervical carcinoma and 17 control subjects were studied
      to determine immunocompetence as a prerequisite for immunotherapy using live
      virus vectors. T-cell immunity, measured by surface phenotype and proliferative
      assays, was reduced with increasing volume of invasive disease, and independent
      of treatment effects. Both the CD4+ and CD8+ subsets were affected so that the
      CD4:8 ratio remained within normal limits. In contrast B-cell number,
      immunoglobulins and complement were normal as were in vivo responses to a
      polysaccharide vaccine. Thus, determination of immunocompetence prior to use of
      live vector immunotherapy requires assessment of each individual subject,
      especially in those with advanced disease.

PMID- 11578519
TI  - Carboplatin and etoposide as first-line chemotherapy in advanced epithelial
      ovarian cancer.
AB  - Carboplatin and etoposide are chemotherapeutic agents active in ovarian cancer,
      previously proved to have a synergistic activity in animal models. The objective
      of this phase II study was to determine the feasibility and the efficacy of the
      combination of carboplatin and etoposide in previously untreated patients with
      advanced epithelial ovarian cancer. Carboplatin, 400 mg m-2 day 1, and etoposide,
      100 mg m-2 days 1-3 every 4 weeks were administered to 28 patients with advanced
      stage (III-IV) ovarian cancer and a performance status 0-2 (ECOG scale), as a
      firstline chemotherapy. Twenty-three patients were evaluable for response; 15
      (65%) (95% CI: 45-81%) responded, 10 (43%) (95% CI: 25-63%) with clinical
      complete response. Pathologic complete response demonstrated during
      postchemotherapy laparotomy was noted in 5/23 (22%) (95% CI: 9-42%) patients. The
      median progression-free interval was 8.5 months, and median survival was 19.5
      months. Toxicity, mainly hematologic, was severe. Nine (32%) patients experienced
      at least one episode of leucopenic fever, which consequently led to toxic deaths
      in two (7%) patients. The relatively low response and survival rates with
      increased toxicity rate are disappointing.

PMID- 11578520
TI  - Conclusions and recommendations from the Helene Harris Memorial Trust Fifth
      Biennial International Forum on Ovarian Cancer, May 4-7, 1995, Glasgow, UK.
AB  - The Fifth Biennial International Forum on Ovarian Cancer was held by the Helene
      Harris Memorial Trust in Glasgow, UK. The main points of the presentations given
      by the invited speakers, together with the fruits of extensive discussions are
      presented here as a series of conclusions and recommendations which should be
      given consideration by all those having an interest in researching or treating
      ovarian cancer. The individual points are grouped into topics considering whether
      there is an identifiable ovarian pro-cancer, whether ovarian cancer is
      preventable, advances in familial ovarian cancer, its molecular genetics, ways of
      optimizing treatment, obstacles to successful treatment and approaches to gene
      therapy.

PMID- 11578521
TI  - Transplantation of congenital primitive neuroectodermal tumor of fetus to the
      uterus of mother: application of biotin-labeled chromosome-specific probes.
AB  - We report a 38-year-old gravida 3, para 3, white female with an unremarkable
      history and normal amniocentesis, who delivered a male infant with a large
      pedunculated and ulcerated tumor by vaginal delivery. A portion of the tumor was
      sheared and expelled with the normal placenta at the time of delivery. The biopsy
      of the infant mass and the expelled tissue showed histologic features of a small
      round cell tumor with immunohistochemical features of a primitive neuroectodermal
      tumor (PNET). The infant eventually died at the age of 4 weeks as a result of
      extensive dissemination of tumor. The mother had postpartum bleeding, and
      fractional dilation and curettage procedures at 6 weeks and 4 months after
      delivery revealed tumor similar to that of the infant. The mother underwent
      radical hysterectomy and bilateral salpingo-oophorectomy, which revealed a
      neoplasm at the junction of the lower uterine segment and cervix. Fluorescent in
      situ hybridization (FISH) study of both the infant's tumor and the mother's
      uterine tumor showed positivity for the Y chromosome by using a classical alpha
      satellite Y chromosome-specific probe. These findings support the hypothesis that
      the tumor was transferred from the fetus to the mother.

PMID- 11578522
TI  - Is there such a thing as a healthy appetite?
AB  - Not surprisingly, since we have a need to live, grow and reproduce, evolution has
      equipped us with a powerful drive to seek food and devour it. If that is not
      enough, our hedonistic emotions have made eating and drinking a pleasurable
      experience. So, what tells us to stop eating? Have we evolved systems to do so
      effectively? The ever increasing problems of excess weight and obesity would
      suggest not.

PMID- 11578523
TI  - Oestrogen receptor beta-immunoreactivity in gonadotropin releasing hormone
      expressing neurones: regulation by oestrogen.
AB  - Double-label immunohistochemistry was employed to establish whether
      immunoreactivity for the beta subtype of the oestrogen receptor (ER beta-IR) is
      present in gonadotropin releasing hormone (GnRH)-containing cells. In the
      immortalized GnRH cell line, GT1-7, almost all nuclei were immunoreactive for ER
      beta. In the preoptic area of ovariectomized rats, more than one-half of the GnRH
      neurones (52.0-63.5%) contained ER beta-IR within the nucleus; a smaller
      proportion of these neurones (5-10%) displayed a particularly intense nuclear
      signal for ER beta. The presence of ER beta-IR in the nuclei of GT1-7 cells and
      GnRH neurones is consistent with recent reports of ER beta mRNA in these cells.
      Oestrogen treatment reduced the percentage of GnRH neurones with detectable ER
      beta-IR. The range of signal intensity for ER beta and the incidence of the ER
      beta signal in GnRH neurones were comparable following double-label
      immunohistochemistry involving either bright field or fluorescent techniques.
      These findings raise the possibility that ER beta receptors mediate direct
      effects of oestrogen on GnRH neurones.

PMID- 11578524
TI  - Action of glucocorticoids on survival of nerve cells: promoting neurodegeneration
      or neuroprotection?
AB  - Extensive studies during the past decades provided compelling evidence that
      glucocorticoids (GCs) have the potential to affect the development, survival and
      death of neurones. These observations, however, reflect paradoxical features of
      GCs, as they may be critically involved in both neurodegenerative and
      neuroprotective processes. Hence, we first address different aspects of the
      complex role of GCs in neurodegeneration and neuroprotection, such as
      concentration dependent actions of GCs on neuronal viability, anatomical
      diversity of GC-mediated mechanisms in the brain and species and strain
      differences in GC-induced neurodegeneration. Second, the modulatory action of GCs
      during development and ageing of the central nervous system, as well as the
      contribution of altered GC balance to the pathogenesis of neurodegenerative
      disorders is considered. In addition, we survey recent data as to the possible
      mechanisms underlying the neurodegenerative and neuroprotective actions of GCs.
      As such, two major aspects will be discerned: (i) GC-dependent offensive events,
      such as GC-induced inhibition of glucose uptake, increased extracellular
      glutamate concentration and concomitant elevation of intracellular Ca(2+),
      decrease in GABAergic signalling and regulation of local GC concentrations by 11
      beta-hydroxysteroid dehydrogenases; and (ii) GC-related cellular defence
      mechanisms, such as decrease in after-hyperpolarization, increased synthesis and
      release of neurotrophic factors and lipocortin-1, feedback regulation of Ca(2+)
      currents and induction of antioxidant enzymes. The particular relevance of these
      mechanisms to the neurodegenerative and neuroprotective effects of GCs in the
      brain is discussed.

PMID- 11578525
TI  - Oestradiol increases phosphorylation of a dopamine- and cyclic AMP-regulated
      phosphoprotein (DARPP-32) in female rat brain.
AB  - Recent studies suggest that oestrogen and progestin receptors may be activated by
      the neurotransmitter dopamine, as well as by their respective ligands. Because
      intracerebroventricular infusion of D(1), but not D(2), dopaminergic receptor
      agonists increases oestrous behaviour in oestradiol-primed rats, we wanted to
      determine if treatment with oestradiol alters the activity of D(1) receptor
      associated processes in steroid receptor-containing areas in female rat brain.
      One D(1) receptor-associated phosphoprotein that may be influenced by oestradiol
      is a dopamine- and cyclic AMP-regulated phosphoprotein, Mr = 32,000 (DARPP-32).
      Because DARPP-32 is phosphorylated in response to dopamine acting via a cAMP
      dependent protein kinase, it provides a useful marker to examine where in the
      brain a particular stimulus might be altering the activity of D(1) receptor
      containing neurones. To determine if oestradiol alters the phosphorylation of
      DARPP-32, we stained immunocytochemically brain sections of female rats treated
      with behaviourally relevant doses of oestradiol or oil vehicle with an antibody
      that detects only the threonine 34-phosphorylated form of DARPP-32. Behaviourally
      effective doses of oestradiol increase the phosphorylation of DARPP-32 within the
      medial preoptic nucleus, bed nucleus of the stria terminalis, paraventricular
      nucleus of the hypothalamus and the ventromedial nucleus of the hypothalamus, 48
      h after treatment. These data suggest that oestradiol increases the activity of
      D(1) dopamine receptor-associated processes in oestrogen receptor-containing
      areas of female rat forebrain.

PMID- 11578526
TI  - Regulation of rat adrenal vasoactive intestinal peptide content: effects of
      adrenocorticotropic hormone treatment and changes in dietary sodium intake.
AB  - Vasoactive intestinal peptide (VIP) is well established as a paracrine regulator
      of adrenal function. It is present in nerves supplying the adrenal cortex,
      although previous studies have found that the amount of VIP in the outer zones of
      the rat adrenal is not affected by ligating the splanchnic nerve supplying the
      adrenal gland. The present studies were designed to investigate the mechanisms
      involved in regulating the VIP content of the rat adrenal gland. This study
      examined the effects of changes in electrolyte balance and adrenocorticotropic
      hormone (ACTH) administration on the adrenal content of VIP as measured by
      radioimmunoassay. Rats on a low sodium diet had a significantly increased
      capsular/zona glomerulosa immunoreactive VIP (irVIP) level, while rats on a high
      sodium diet had suppressed levels relative to controls. Changes in dietary sodium
      did not affect inner zone/medullary VIP content. Administration of ACTH caused a
      decrease in irVIP levels in the capsular/zona glomerulosa portion of the adrenal
      gland but had no effect on the inner zone/medulla. Analysis of mRNA encoding VIP
      revealed a large increase in expression of VIP in the sodium-deplete group
      compared with the control, with no change in VIP expression in the sodium-loaded
      group. ACTH treatment was found to significantly decrease VIP mRNA levels in the
      capsular portion. Neither ACTH treatment nor changes in sodium intake affected
      inner zones/medullary VIP message. These data suggest that VIP in the capsule and
      zona glomerulosa region of the adrenal cortex is regulated in response to the
      physiological status of the animal, with changes in capsular/zona glomerulosa VIP
      correlating with changes in zona glomerulosa function.

PMID- 11578527
TI  - Polyamine regulation of the rat pro-opiomelanocortin gene expression in AtT-20
      cells.
AB  - Polyamines are a ubiquitous group of amines that play diverse biological roles.
      In the anterior pituitary, intracellular polyamine levels are reported to show
      diurnal changes, although the biological significance remains to be elucidated.
      In this study, we examined the effects of polyamines on the transcriptional
      activity of the rat pro-opiomelanocortin (POMC) gene using AtT20PL, a clone of
      the AtT20 cell line in which an approximately 0.7 kb of the rat POMC 5' promoter
      luciferase fusion gene was stably incorporated. The results showed that three
      representative polyamines (putrescine, spermidine and spermine) all stimulated
      POMC promoter activity in a time- and dose-related manner, spermine showing the
      most potent effect (maximum approximate three-fold increase). This effect was not
      observed under treatment with actinomycin D, suggesting the effect of polyamine
      at the transcriptional level. On the other hand, methylglyoxal bis
      (guanylhydrazone), an inhibitor of polyamine synthesis, showed the opposite
      effect, further supporting the positive role of intracellular polyamines. Taken
      together, our findings suggest that polyamines are involved in the regulation of
      POMC gene expression (especially in terms of diurnal changes) in corticotroph
      cells. The precise molecular mechanisms of polyamine effects await further
      research.

PMID- 11578528
TI  - Crosstalk between oestrogen receptors and thyroid hormone receptor isoforms
      results in differential regulation of the preproenkephalin gene.
AB  - Nuclear receptors are ligand-activated transcription factors, which have the
      potential to integrate internal metabolic events in an organism, with
      consequences for control of behaviour. Previous studies from this laboratory have
      shown that thyroid hormone receptor (TR) isoforms can inhibit oestrogen receptor
      (ER)alpha-mediated induction of preproenkephalin (PPE) gene expression in the
      hypothalamus. Also, thyroid hormone administration inhibits lordosis, a behaviour
      facilitated by PPE expression. We have examined the effect of multiple ligand
      binding TR isoforms on the ER-mediated induction of the PPE gene in transient
      transfection assays in CV-1 cells. On a natural PPE gene promoter fragment
      containing two putative oestrogen response elements (EREs), both ER alpha and
      beta isoforms mediate a four to five-fold induction by oestrogen. Cotransfection
      of TR alpha 1 along with ER alpha inhibited the ER alpha transactivation of PPE
      by approximately 50%. However, cotransfection with either TR beta 1 or TR beta 2
      expression plasmids produced no effect on the ER alpha or ER beta mediated
      induction of PPE. Therefore, under these experimental conditions, interactions
      with a single ER isoform are specific to an individual TR isoform. Transfection
      with a TR alpha 1 DNA-binding mutant could also inhibit ER alpha transactivation,
      suggesting that competition for binding on the ERE may not be the exclusive
      mechanism for inhibition. Data with the coactivator, SRC-1, suggested that
      coactivator squelching may participate in the inhibition. In dramatic contrast,
      when ER beta is cotransfected, TR alpha 1 stimulated ER beta-mediated
      transactivation of PPE by approximately eight-fold over control levels. This is
      the first study revealing specific interactions among nuclear receptor isoforms
      on a neuroendocrine promoter. These data also suggest that the combinatorics of
      ER and TR isoforms allow multiple forms of flexible gene regulations in the
      service of neuroendocrine integration.

PMID- 11578529
TI  - Food restriction affects the gonadotropin releasing hormone neuronal system of
      male prairie voles (Microtus ochrogaster).
AB  - Individuals of species inhabiting temperate and boreal latitudes optimize the
      timing of energetically costly processes by curtailing nonessential energetically
      demanding processes when environmental conditions are not favourable. One
      proximate environmental variable used to fine-tune moment-to-moment changes in
      reproductive physiology and behaviour is food intake. The neuroendocrine
      mechanisms by which food restriction leads to the cessation of reproduction in
      seasonally breeding rodent species remain largely unspecified. The present study
      sought to determine the effects of extended food restriction on the gonadotropin
      releasing hormone (GnRH) neuronal system. Male prairie voles (Microtus
      ochrogaster) were either fed ad libitum or were exposed to either 1, 2 or 3 weeks
      of moderate (70% of daily mean) food restriction. In accordance with previous
      studies of food restriction, gross reproductive organ masses and body mass were
      unaffected by food deprivation. Although 1 week of food restriction did not
      result in alterations in the GnRH neuronal system, food restriction for 2 weeks
      was associated with increased GnRH-immunoreactive (GnRH-ir) neurone soma size.
      Three weeks of food restriction resulted in a pronounced increase in GnRH-ir
      neurone numbers, as well as an increase in fibre intensity in the main fibre
      pathway to the median eminence. Taken together, these findings suggest that
      extended food restriction leads to modifications in the GnRH neuronal system,
      providing a means for temporary cessation of reproduction without gross
      alterations in reproductive physiology. This transient change in the hypothalmo
      pituitary-gonadal axis, without pronounced changes in reproductive organ
      morphology, likely provides a mechanism for the rapid reinitiation of breeding in
      nature when local conditions provide adequate food availability.

PMID- 11578530
TI  - Altered regulation of gene and protein expression of hypothalamic-pituitary
      adrenal axis components in an immature rat model of chronic stress.
AB  - Chronic stress early in postnatal life influences hormonal and behavioural
      responses to stress persistently, but the mechanisms and molecular cascades that
      are involved in this process have not been clarified. To approach these issues, a
      chronic stress paradigm for the neonatal rat, using limited bedding material to
      alter the cage environment, was devised. In 9-day-old rats subjected to this
      chronic stress for 1 week, significant and striking changes in the expression and
      release patterns of key molecules that govern the neuroendocrine stress responses
      were observed. The presence of sustained stress was evident from enhanced
      activation of peripheral elements of the neuroendocrine stress response, i.e.
      increased basal plasma corticosterone concentrations, high adrenal weight and
      decreased body weight. Central regulatory elements of the neuroendocrine stress
      response were perturbed, including reduced expression of hypothalamic
      corticotropin-releasing hormone that, surprisingly, was accompanied by reduced
      glucocorticoid receptor expression. Thus, the effects of chronic sustained stress
      in the neonatal rat on the hypothalamic-pituitary-adrenal axis included
      substantial changes in the expression and activity of major regulators of this
      axis. Importantly, the changes induced by this chronic stress differed
      substantially from those related to acute or recurrent stress, providing a novel
      model for studying the long-term effects of chronic, early life stress on
      neuroendocrine functions throughout life.

PMID- 11578531
TI  - Ablation of pituitary pro-opiomelanocortin (POMC) cells produces alterations in
      hypothalamic POMC mRNA levels and midbrain mu opioid receptor binding in a
      conditional transgenic mouse model.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is regulated by stress-related
      excitatory inputs, and various inhibitory and negative-feedback controls by
      glucocorticoids and opioids, including pro-opiomelanocortin (POMC)-derived
      peptides. The role of POMC-derived peptides of pituitary origin in the modulation
      of brain POMC mRNA expression and opioid receptor binding was investigated using
      a line of transgenic mice that express a fusion gene composed of the pituitary
      expression-specific promoter region of the POMC gene driving the herpes simplex
      viral-1 thymidine kinase (TK). Male adult mice were treated with the antiherpes
      agent ganciclovir that selectively ablates cells expressing TK. Following
      treatment, POMC mRNA levels, measured by quantitative solution
      hybridization/RNase protection assays, were decreased by 48% in the pituitary of
      the TK+/+ mice, reflecting an expected loss of the pituitary corticotrope POMC
      cells. This treatment also significantly lowered pituitary beta-endorphin
      immunoreactivity content and plasma concentrations of corticosterone. In
      contrast, POMC mRNA levels were increased by 79% in the hypothalamus of the TK+/+
      mice with pituitary POMC cell ablation. Binding of [(3)H]DAMGO to mu opioid
      receptors, as measured by quantitative autoradiography, was significantly reduced
      in several brain regions including the central grey, median raphe and superficial
      grey layer of the superior colliculus. These regions are innervated by
      hypothalamic POMC neurones. No significant differences in binding to either kappa
      or delta opioid receptors were found in the brain regions studied. These results
      suggest that POMC-derived peptides of pituitary origin may exert a tonic negative
      feedback effect on hypothalamic POMC neurones. In turn, the downregulation of
      central mu opioid receptors in this model may be mediated through a mechanism
      related to hypothalamic POMC overexpression.

PMID- 11578532
TI  - Differential expression of vasoactive intestinal polypeptide receptor 1 and 2
      mRNA in murine intestinal T lymphocyte subtypes.
AB  - Neuropeptides may exert a variety of effects on the immune cells at both systemic
      and mucosal immune sites. The immunoregulatory properties refer to the ability of
      physiological signals and pathways to influence various immune functions.
      Vasoactive intestinal polypeptide (VIP), a neuropeptide present in high
      concentration in gut, was studied for its production and receptor expression in
      intraepithelial and lamina propria T lymphocytes of mouse intestine. Using
      reverse transcription-polymerase chain reaction (RT-PCR) analysis, it was
      demonstrated that VIP receptor 1 (VIPR1) was constantly expressed in
      intraepithelial and lamina propria T lymphocytes from both small and large
      intestine. In contrast, VIPR2 was identified only in T cells from small
      intestine. Further studies on purified subpopulations of T lymphocytes indicated
      the existence of VIPR2 in CD8(+) T cells, but not CD4(+) and CD4CD8 double
      negative T cells, although all these three subpopulations displayed VIPR1. In
      addition, VIPR1 mRNA was detected in splenic T lymphocytes, but no signal was
      obtained for VIPR2 mRNA, even after stimulation of the cells with anti
      CD3(epsilon)-chain mAb, phorbol 12-myristate 13-acetate (PMA) and/or VIP. The
      presence of VIP receptor(s) on intestinal T lymphocytes was supported by the
      detection of VIP on the cell surface using dual colour immunoflowcytometry. In
      vitro treatment with VIP resulted in a tendency towards an increased size of the
      VIP immunoreactive T cell population and significantly enhanced the average
      immunofluorescence intensity of the surface labelling. This indicates that the
      receptors are partially occupied by locally produced VIP in vivo and that more
      peptide molecules can be bound on the lymphocytes when needed, released and
      accumulated in higher concentration at the action sites. We failed to detect the
      expression of VIP mRNA in T lymphocytes, from either intestine or spleen. These
      observations support that VIP may be an important immune modulator in gut acting
      through specific receptors on T lymphocytes. The differential mRNA expression of
      VIP receptor subtypes in cells with different phenotypes and in different immune
      compartments may suggest diverse regulatory roles of the neuropeptide in immune
      responses.

PMID- 11578534
TI  - [Bronchiolitis: the need for a care consensus].

PMID- 11578533
TI  - A new perspective on glucocorticoid feedback: relation to stress, carbohydrate
      feeding and feeling better.
AB  - Input to and regulation of activity in the hypothalamic-pituitary-adrenal (HPA)
      axis is diverse and complex. Glucocorticoid feedback is a major component that
      determines activity in this classic neuroendocrine axis and, while feedback
      occurs through the brain, the pathways that mediate glucocorticoid feedback
      remain unknown. In this review, I discuss findings that have led us to view
      glucocorticoid feedback in the HPA axis in a new light. Much of what has
      precipitated this view comes from a very surprising finding in our laboratory;
      sucrose ingestion normalizes feeding, energy balance and central corticotropin
      releasing factor expression in adrenalectomized (ADX) rats. Since this discovery,
      a diverse set of literature that supports this view of glucocorticoid feedback
      has been found. Taken together, recent findings of the well-known importance of
      glucocorticoids to feeding and energy balance, and the modulatory actions of
      carbohydrate ingestion on both basal and stress-induced activity in the HPA axis,
      strongly suggest that many metabolic (e.g. obesity) and psychological (e.g.
      depression) pathologies, which often present together and have been associated
      with stress and HPA dysregulation, might, in part, be understood in light of our
      new view of glucocorticoid feedback.

PMID- 11578535
TI  - [Prevalence of low height and related risk factors in school children from
      Corrientes (Argentina)].
AB  - BACKGROUND: Height is the anthropometric indicator that best reflects the
      interaction between genetic and environmental factors. OBJECTIVE: The objective
      of this study was to measure height and to identify risk factors for low height
      in school children from Corrientes in Argentina. POPULATION AND METHODS: Between
      March and December 2000, a cross-sectional study was performed in 2,282 school
      children of both sexes, aged 6-14 years old, from two inner-city schools and two
      schools in the outskirts of the city. The variables studied were age, height,
      weight, birth weight, breastfeeding, maternal education and socioeconomic status.
      The values for height were turned into Z scores, and then compared with the
      reference standards of the National Center for Health Statistics in the United
      States. The statistical analysis was performed using the Chi-squared test for
      qualitative variables and ANOVA for quantitative variables. A significance of p <
      0.05 was accepted. RESULTS: Prevalence of height below 2 standard deviation units
      and below 1 standard deviation unit was 4.6 % and 25.1 %, respectively. Maternal
      illiteracy, low birth weight, absence of breastfeeding and low socioeconomic
      status were significantly associated with low height. CONCLUSIONS: The prevalence
      of low height in this study was similar to that in other Latin-American
      countries. In our study the absence of breastfeeding, maternal illiteracy, low
      birth weight and low socioeconomic status were risk factors for low height.

PMID- 11578536
TI  - [Uric acid as a prognostic marker in critically ill patients].
AB  - BACKGROUND: Elevated uric acid concentrations reflect adenosine triphosphate
      degradation and suggest poor prognosis since they indicate a cellular
      bioenergetic crisis. OBJECTIVE: To study uric acid concentrations as a prognostic
      marker of disease severity in critically ill children. PATIENTS AND METHODS:
      Seventy-eight patients admitted to our pediatric intensive care unit with
      different diseases were prospectively studied. Thirty-five patients with
      meningococcal infection were retrospectively studied. Data on uric acid
      concentrations, diagnosis, length of stay, age, weight, the therapeutic
      intervention scoring system (TISS) and the pediatric risk of mortality score
      (PRISM) were collected. In patients with meningococcal infection severity was
      evaluated by studying evolution (death and the presence of sequelae or
      otherwise). RESULTS: Uric acid concentrations on admission were significantly
      correlated with TISS on the first day (r 0.260; p 0.023) and with PRISM during
      the first 24 hours (r 0.277; p 0.015). In patients without craniocerebral trauma,
      correlations between uric acid concentrations and PRISM during the first 24 hours
      (r 0.524; p < 0.001) and correlations between uric acid concentrations with TISS
      on day 1 (r 0.483; p < 0.001) and day 2 (r 0.373; p 0.014) improved. In patients
      with craniocerebral trauma no significant correlations were found between uric
      acid and any of the other variables. In patients with meningococcal infection,
      uric acid concentrations on admission were closely related to evolution (uric
      acid concentrations were 13.20 8.2 mg/dl in patients who died, 8.01 1.77 mg/dl in
      those with sequelae and 4.72 1.84 mg/dl in in those without sequelae; p < 0.003).
      CONCLUSIONS: Serum uric acid concentrations can be considered as a marker of
      severity in critically ill patients without craniocerebral trauma and especially
      in patients with meningococcal infection.

PMID- 11578537
TI  - [First urinary tract infection in healthy infants: epidemiology, diagnosis and
      treatment].
AB  - BACKGROUND: Urinary tract infection (UTI) is one of the most common infections in
      infants. It presents certain peculiarities compared with other pediatric age
      groups in terms of symptomatology, diagnosis and the therapeutic approach
      employed to prevent sequels. OBJECTIVE: To analyze the epidemiology, clinical and
      laboratory findings, etiology, diagnosis and treatment of first-time UTI in
      healthy infants. MATERIAL AND METHODS: Between January and December 1999, we
      performed a retrospective study of 131 previously healthy infants admitted to our
      hospital with a diagnosis of first-time UTI. Demographic data, clinical
      characteristics, urine dipstick, urinalysis and urine culture (vesical
      catheterization), blood cell count and PCR, kidney ultrasonography, voiding
      cystourethrogram and DMSA scintigraphy were reviewed. RESULTS: We studied 131
      patients (median age: 90 days). In infants younger than 30 days, UTI was more
      prevalent in males. The most frequent symptom was fever (73.3 %). Seventy-one
      patients fulfilled the criteria for acute pyelonephritis. The presence of
      nitrituria was low. Escherichia coli was isolated in 90.1 % of the patients.
      Voiding cystourethrogram detected vesicoureteric reflux in 18.4 % of the
      patients. Scintigraphy revealed renal scarring in 15.1 %. No significant
      correlations were found between renal scarring in late scintigraphy and a
      diagnosis of acute pyelonephritis and/or alterations in the cystourethrogram.
      CONCLUSIONS: Fever was the main symptom. E. coli was the most commonly isolated
      microorganism. Nitrituria had low sensitivity in infants. Ultrasonography had low
      specificity. Scintigraphy showed the highest sensitivity and specificity in the
      detection of renal scarring. Predictability improved when scintigraphy was
      performed a few months after acute infection.

PMID- 11578538
TI  - [Pneumococcal meningitis: epidemiological, clinical and bacteriological
      characteristics].
AB  - OBJECTIVE: To analyze the epidemiological and clinical features of pneumococcal
      meningitis. PATIENTS AND METHODS: We performed a retrospective study of 53 cases
      of pneumococcal meningitis that occurred in 47 pediatric patients in our hospital
      between 1977 and 2000. Four children had recurrent meningitis. In all patients
      Streptococcus pneumoniae was isolated from cerebrospinal fluid culture. The
      epidemiological, bacteriological and clinical characteristics were studied.
      RESULTS: Pneumococcal meningitis represented 6 % of bacterial meningitis in our
      environment with 2-3 cases registered per year. Seventy-two percent of cases
      occurred in winter and spring. The age of affected children was between 1 month
      and 13 years. Sixty-five percent of children older than 2 years had a
      predisposing disease. Penicillin-resistant strains were detected in 1990 and
      cefotaxime-resistant strains were isolated in 1994. Seven children (13 %) had
      severe neurological sequels and two (4 %) died. CONCLUSIONS: Pneumococcal
      meningitis produces higher morbidity and mortality than other types of bacterial
      meningitis. The disease usually affects children younger than 2 years and older
      children with a predisposing disease. In the last few years, the importance of
      pneumococcal meningitis has increased due to the lower incidence of other types
      of bacterial meningitis. Because of beta-lactam resistant strains, initial
      empirical treatment should include vancomycin. The above data suggest the
      advisability of the generalized use of heptavalent pneumococcal conjugate vaccine
      in the pediatric population in our environment.

PMID- 11578539
TI  - [Procalcitonin in the early diagnosis of invasive bacterial infection in febrile
      infants].
AB  - BACKGROUND: Procalcitonin (PCT) it is a new marker of bacterial infection.
      Because of its shorter half-life and earlier ascent it offers advantages over C
      reactive protein (CRP). OBJECTIVE: To compare the diagnostic performance of PCT
      in the early detection of invasive bacterial infection in infants with that of
      CPR. MATERIAL AND METHODS: Between January of 1998 and February of 2000 we
      performed a prospective observational study in the emergency department of
      infants aged between 1 and 36 months who had been treated for fever and for whom
      PCT and CRP plasmatic values had been obtained. Plasmatic PCT and PCR values were
      evaluated and correlated with the final diagnosis. ROC curves for both markers
      were calculated. RESULTS: One hundred infants with a mean age of 8.8 months (SD
      7.59) were included in four groups of 25 patients each (viral infection,
      localized bacterial infection, invasive bacterial infection and control group).
      The mean PCT and CRP values in invasive bacterial infections [PCT: 14.45 ng/mL
      (SD 27.95) and CRP: 95.10 mg/L (SD 7 2.77)] were significantly higher than in non
      invasive infections [PCT: 0.27 ng/mL (SD 0.19) and CRP: 25.67 mg/L (SD 33.04)]
      but the diagnostic performance of PCT was better. The area under the curve for
      PCT was 0.95 (SD 0.03), which was significantly higher (p < 0.001) than that
      obtained for CRP [0.81 (SD 0.05)]. The optimal cut-off for PCT was > 0.4 ng/mL
      (sensitivity: 95.5 %; specificity: 86.4 %) and that for CRP was > 42.9 mg/L
      (sensitivity: 75 %; specificity: 81.8 %). In infants who had fever for less than
      12 hours (n 30) the area under the curve for PCT was 0.90 (SD 0.06), which was
      higher (p < 0.001) than that for PCR [0.64 (SD 0.11)]. The optimal cut-off for
      PCT in this group was > 0.4 ng/mL (sensitivity: 90 %; specificity: 94 %) and that
      for CRP was > 26.6 mg/L (sensitivity: 60 %; specificity: 77.8 %). CONCLUSIONS:
      The diagnostic performance of PCT was higher than that of CRP in the early
      detection of invasive infection in febrile infants, even when evolution was less
      than 12 hours.

PMID- 11578540
TI  - [Psychological intervention for treatment compliance in chronic pediatric
      diseases].
AB  - This paper analyses the problems of treatment adherence in chronic pediatric
      diseases from a psychological point of view. We describe the repercussions of
      adherence on the course of the disease, the physician in charge, patients, and
      their relatives and place special emphasis on the complexity of the problem among
      adolescents. Factors impeding adherence are reviewed and factors related to
      disease and treatment, as well as cognitive, emotional, behavioral, familial,
      social, cultural, organizational and economic variables, are identified. The
      author proposes a psychological intervention that includes the assessment,
      prevention and management of problems of treatment adherence. The indications and
      implementation of each technique are outlined, distinguishing among educational,
      motivational and behavioral strategies. In summary, a psychological treatment
      program is proposed that may be easily applied to a large number of pediatric
      patients with chronic diseases and suspected or confirmed problems of treatment
      adherence.

PMID- 11578541
TI  - [Association between heroin consumption in pregnancy and structural abnormalities
      of the respiratory cilia in newborn infants].
AB  - OBJECTIVE: To describe structural abnormalities of the respiratory cilia in
      newborn infants whose mothers consumed heroin during pregnancy. PATIENTS AND
      METHODS: The medical records of 295 newborn infants whose mothers consumed heroin
      either throughout or at some time during pregnancy and who were cared for in
      Hospital del Mar in Barcelona (Spain) between January 1982 and December 1997 were
      reviewed. Seven infants with neonatal respiratory distress after the withdrawal
      syndrome period were selected. Diagnoses were established by electron microscopy
      of nasal mucosa samples. RESULTS: All seven newborns with prolonged neonatal
      respiratory distress had ultrastructural abnormalities of the ciliary axoneme
      similar to those of primary ciliary dyskinesia or immotile cilia syndrome. The
      incidence of this alteration in this series was higher than that in the general
      population. CONCLUSIONS: These data suggest a possible association between
      ultrastructural abnormalities of the ciliary axoneme and prolonged neonatal
      respiratory distress in the infants of heroin-consuming mothers.

PMID- 11578543
TI  - [Anorectal and external genitalia malformation associated with perineal
      hemangioma].
AB  - We describe a girl with anorectal and genitourinary malformation with perineal
      hemangioma. Posterior sagittal anorectoplasty was performed at 21 months of age
      with good functional results. The hemangioma required no treatment and involuted
      spontaneously when the patient was 6 years old. Although anorectal malformations
      are frequently associated with multiple congenital anomalies, the association
      described herein is uncommon and we found only three similar cases reported in
      the medical literature.

PMID- 11578542
TI  - [Familial junctional ectopic tachycardia: clinical and pathological findings].
AB  - We describe two brothers with a neonatal diagnosis of junctional ectopic
      tachycardia. The first brother presented hydrops fetalis secondary to narrow QRS
      tachycardia at a rate of 230-300 beats/min with atrioventricular dissociation.
      Although the ventricular rate was controlled with intravenous amiodarone the baby
      died a few hours after initiation of this treatment from ventricular fibrillation
      and electromechanical dissociation. Histological examination of the conduction
      system showed diffuse hemorrhage and necrosis of the atrioventricular node and
      His' bundle. The second brother presented fetal distress and polyhydramnios and
      the postnatal electrocardiogram revealed junctional ectopic tachycardia at a rate
      of 170 beats/min alternating with sinus rhythm, which was controlled without
      treatment.

PMID- 11578544
TI  - [Acute bronchiolitis: evaluation of evidence-based therapy].
AB  - Bronchiolitis is the leading cause of lower respiratory tract infection in
      infants and produces significant morbidity. Limited progress has been made in the
      treatment of this disease and, in many cases, the therapy employed is
      controversial and mainly based on general recommendations and not on evidence
      based strategies. This report uses evidence-based methodology to provide a
      critical review of the data available on the treatment of acute bronchiolitis
      (understood as the first episode of respiratory syncytial virus bronchiolitis in
      a previously healthy infant). After this analysis, we conclude that the only
      justifiable therapeutic interventions in these patients are supportive treatment,
      nebulized epinephrine and mechanical ventilation. Other therapies such us
      physiotherapy, nebulization, heliox, anticholinergics or exogenous surfactant,
      among others, require further randomized controlled trials to determine their
      utility. No evidence supports the routine use of corticosteroids, beta-adrenergic
      drugs, antibiotics, immunoglobulins, interferon, vitamin A or ribavirin in these
      patients. Finally, we consider that a national consensus review for the
      implementation of evidence-based clinical practical guidelines on the management
      of acute bronchiolitis would be of great interest.

PMID- 11578545
TI  - [Acute bronchiolitis: fundamentals of a rational protocol].
AB  - Bronchiolitis is the most frequent respiratory tract disease in the first 2 years
      of life. It occurs in epidemics in winter and spring. Etiology is viral and the
      most frequent causative agent is respiratory syncytial virus. In most patients
      the disease is benign and self-limiting and only occasionally requires
      hospitalization. In daily clinical practice, one of the problems most frequently
      faced by the pediatrician is the lack of agreement on the correct pharmacological
      treatment of bronchiolitis, as well as the absence of simple, or standardized,
      clinical scores with which to diagnose severity. The present study provides a
      review of the medical literature on the most commonly used clinical scores and
      the therapeutic efficacy of the different drugs employed. A protocol for the
      practical management of bronchiolitis is provided. The use of inhaled adrenaline
      in the treatment of moderate-to-severe bronchiolitis in hospitalized infants, as
      well as oxygen and fluid therapy as support measures, are recommended.

PMID- 11578546
TI  - [Splenic abscess and cat-scratch disease].
AB  - Cat-scratch disease is caused by a Gram-negative bacillus known as Bartonella
      henselae. This disease is usually benign and causes regional adenitis that does
      not require treatment. However, some patients develop more serious atypical forms
      of the disease including prolonged systemic illness with hepatic and splenic
      abscesses.A 14-year-old girl was admitted to hospital with a 12-day history of
      persistent high fever and abdominal pain. Ultrasonography and computerized
      tomography of the abdomen revealed splenic abscesses. These findings, together
      with an antecedent of cat exposure, led to the suspicion of cat-scratch disease,
      which was confirmed by serology. The girl was treated with intramuscular
      ceftriaxone and clinical evolution was favorable. Splenic cat-scratch disease is
      infrequent. Cat-scratch disease sometimes presents as fever of unknown origin and
      consequently this disease should be considered in the differential diagnosis of
      prolonged fever. Although evolution is usually favorable, antibiotic therapy is
      recommended in systemic manifestations of cat-scratch disease.

PMID- 11578547
TI  - [Idiopathic purpura fulminans with transient protein S deficiency].
AB  - Idiopathic purpura fulminans produces rapidly progressive hemorrhagic necrosis of
      the skin with disseminated intravascular coagulation in individuals without known
      abnormalities of the protein C pathway or acute infections. The disease mainly
      affects children and in 90 % of cases is preceded by a benign infection. Its
      pathogenesis involves a temporary autoimmune protein S deficiency that provokes a
      state of hypercoagulability. We present the case of a previously healthy 2-year
      old boy with hemorrhagic skin lesions characteristic of purpura fulminans and
      disseminated intravascular coagulation without sepsis. Severe, temporary protein
      S deficiency was confirmed. The patient received daily replacement therapy with
      fresh frozen plasma for 12 days and anticoagulation with heparin for 3 months.
      Evolution was favorable. Although the other parameters returned to normal,
      protein S remained low for 50 days despite treatment. The patient has made a
      complete recovery.

PMID- 11578548
TI  - [Varicella induced rhabdomyolysis].
AB  - Primary varicella-zoster infection is very common during childhood and few
      patients develop complications. The most frequent complications are bacterial
      infection of the lesions, laryngitis and varicella pneumonia. In the nervous
      system it can produce encephalitis and especially cerebellitis. We describe a
      case of primary varicella-zoster induced rhabdomyolysis in a 5-year-old girl with
      mental retardation, microcephalia and mild diplegia who, in the context of
      varicella infection, presented extreme muscular weakness and prostration. Blood
      and urine tests showed high creatine phosphokinase concentrations and
      myoglobinuria. The patient received aggressive intravenous hydration. Evolution
      was favorable with no renal failure. Rhabdomyolysis can produce life-threatening
      complications such as renal failure, intravascular disseminated coagulation and
      hyperkaliemia. The disease can be precipitated by alcohol ingestion, compression
      injury and generalized seizures. Infectious etiology is less common. Few reports
      have been published on primary varicella-zoster induced rhabdomyolysis but,
      because creatine phosphokinase concentrations are not routinely performed in
      varicella infection, very mild cases might have been under-diagnosed. Despite its
      rarity, this disease should be considered in cases of infection, since early
      treatment with hyperhydration can prevent complications.

PMID- 11578549
TI  - [Hospitalization for acute bronchiolitis, gestational age, and palivizumab].

PMID- 11578550
TI  - [Recommendation of vaccination against meningitis C in Cantabria].

PMID- 11578551
TI  - [Primary torsion of the greater omentum in children].

PMID- 11578552
TI  - [Hereditary angioedema].

PMID- 11578553
TI  - [Trichobezoar: a psychological problem].

PMID- 11578554
TI  - [Training activity of the Spanish Pediatrics Association].

PMID- 11578555
TI  - [Parietal holes].

PMID- 11578556
TI  - [From theory to practice: creating health plans for the new century].

PMID- 11578557
TI  - [Authors, reviewers, editors: the rules of the game].

PMID- 11578558
TI  - [Geographical distribution of the male/female ratio of cardiovascular mortality
      in Spain].
AB  - OBJECTIVES: To describe the geographic distribution of the male/female ratio
      (MFR) of mortality from ischaemic heart disease (IHD) and cerebrovascular disease
      (CVD) in 1991-1995 in Spain, and to examine wether the differences between men
      and women in exposure to cardiovascular risk factors could explain such
      distribution. METHODS: Mortality data come from National Vital Statistics. Age
      adjusted mortality rates for the period 1991-1995 were calculated for IHD and CVD
      using the direct method, in population aged 40 to 79 years. Data on tobacco and
      alcohol consumption, hypertension, hypercholesterolemia, diabetes, obesity,
      sedentariness, and health services use come from the 1993 Spanish National Health
      Survey, and socioeconomic data from the 1991 Population Census. Data were
      analyzed by correlation and Poisson regression methods. RESULTS: MFR of mortality
      from IHD and CVD are higher in the provinces of the north of Spain, and are
      correlated negatively with mortality from IHD and CVD. This negative association
      is stronger for mortality in women than in men. Among the risk factors examined,
      only MFR of alcohol consumption showed a significant (p < 0.05) association with
      MFR of mortality from IHD and CVD. MFR of alcohol consumption explains 23 and 14%
      of the provincial variation in MFR of mortality from IHD and CVD, respectively,
      and showed a U shaped relationship with MFR of mortality for both diseases.
      CONCLUSIONS: Provinces in the north of Spain, which register the lowest
      cardiovascular mortality, show the highest MFR of IHD and CVD mortality, because
      of the lower mortality in women than in men. As derived from the dose-response
      relationship between MFR of IHD and CVD mortality and the MFR of alcohol
      consumption, a higher alcohol consumption in men could contribute to a higher MFR
      of cardiovascular mortality in some Spanish provinces.

PMID- 11578559
TI  - [Secular trends in smoking according to educational level between 1986 and 1996:
      The MONICA study. Catalonia].
AB  - OBJECTIVE: To describe trends from 1986-1996 in the prevalence of cigarette
      smoking between ages 25 to 64 in the MONICA-Catalonia study, according to
      educational level, and to validate these trends biochemically. METHODS: Three
      cross-sectional surveys in independent random samples of the general population
      of central Catalonia area carried out in 1986-88, 1990-92 and 1994-96 following
      the World Health Organization's MONICA protocol. Serum thiocyanate was determined
      by the Bowler method. RESULTS: A total of 2,571, 2,934 and 3,485 men and women
      were examined with response rates of 74, 67 and 72% in each survey respectively.
      The age-adjusted cigarette smoking prevalence decreased in men by 5.1% (95% CI:
      1.5 to 8.7) and increased in women by +8.5% (95% CI: +5.6 to +11.4). The
      prevalence was 46.5% in men and 23.9% in women in 1994-96. The greatest decrease
      was in men aged 55-64 (9.9%) and the greatest increase was in women aged 35-44
      (+14.8%). These trends were confirmed by serum thiocyanate levels, which
      decreased from 78.9 to 73.9 MUmol/l (p = 0.07) in men and increased from 43.7 to
      49.8 MUmol/l (p < 0.01) in women during the study period. Cigarette smoking
      increased in less educated women (+10%) and decreased in university women (6%),
      while cigarette smoking in men decreased irrespective of educational level. Serum
      thiocyanate levels confirmed the relationship with educational level.
      CONCLUSIONS: The prevalence of cigarette smoking decreased in men between 1986
      and 1996 but remained high in 1996. Women showed a pattern of progressive
      adoption of smoking, especially those with lower educational level.

PMID- 11578560
TI  - [Can we help our patients to stop smoking?: the experience of the Smoking
      Cessation Program].
AB  - OBJECTIVE: To describe the process and results of the Smoking Cessation Program
      in order to answer this question: Does the lack of time and resources justify
      poor involvement of physicians in helping patients to stop smoking? METHODS:
      Prospective series of cases that included all smokers (n = 1203) who for any
      reason attended seven general practices over a period of one year. The behaviour
      of smokers when the program was offered as well as the workload generated by the
      implementation of the process are described. Subjects who stopped smoking were
      those who did not smoke two years after enrolment in a sustained and validated
      form for least 12 months. RESULTS: A total of 7.3% of all smokers quit (95%
      confidence interval [CI]: 5.9-8.9). Enrolment of subjects caused an increase in
      the consultation time of 23 seconds and decreased from a mean of 30 new smokers
      per month per practice during the first three months to 12 at the end of the
      first year. All received advise to stop smoking (mean increase of 3 min and 33 s)
      but only 17.5% accepted the therapeutic plan during the first year (95% CI: 15.4
      19.9) that had a duration of 72:11 min and generated a mean of six programmed
      appointments a month in each practice. Twenty percent of subjects who
      participated in the therapeutic plan stopped smoking (95% CI: 14.8-26.1).
      CONCLUSIONS: Identification and universal advice to smokers, together with
      treatment of those who are motivated to quit, achieved important success rates
      without increasing excessively ordinary work loads.

PMID- 11578561
TI  - [Problems and proposals for improvement in the health care of economic
      immigrants].
AB  - OBJECTIVES: To analyse existing problems in health care to economic immigrants
      from the point of view of health and social professionals, health authorities and
      economic immigrants and to know which will be their proposals and priorities to
      improve economic immigrants's health assistance. METHODS: Qualitative approach
      study made in Majorca island. (Spain). Three focus groups and three nominal
      groups with health and social workers from primary health care and hospital
      services were carried out as well as two partially structured interviews to
      health authorities, one Autonomic Authority and one Governmental Authority, and
      twelve partially structured interviews to economic immigrants identified trough
      key informants. RESULTS: Health and social workers perceive the increase in the
      number of economic immigrants as a massive arrival. The main problems identified
      are: access restrictions to public health services for economic immigrants, the
      follow-up of these patients and diagnostic difficulties because lack of training
      in tropical medicine. Health and social workers's first proposal for improving
      this situation is their own training in tropical medicine. Autonomic Authority
      priorities are to guarantee access to public health services for all immigrants
      and to look actively for health problems in these population. Governmental
      Authority, instead, holds the legalization for all. In fact, economic immigrants
      are not concerned on health care because legalization and housing problems.
      CONCLUSIONS: The main barriers identified by health and social workers in health
      care to economic immigrants are: access restrictions, follow-up and lack of
      training in tropical medicine. Health and social first proposal to improve this
      situation is their own training in tropical medicine while Autonomic and Central
      Authorities's priorities are not the same. For economic immigrants, health
      assistance is not their biggest concern.

PMID- 11578562
TI  - [Rational prescribing and cost reduction in the treatment of arterial
      hypertension: a simulation exercise].
AB  - INTRODUCTION: Cost of antihypertensive drugs in Spain raises 100.000 millions of
      pesetas. The utilization of new drugs more expensive than classics diuretics and
      beta blockers is the main reason of this cost increase.The Joint National
      Commission on Hypertension 6th Report supports the utilization of diuretics and
      beta blockers as the first choice in patients without any special condition,
      based in their best efficience. Other professional group don't point out any
      therapeutic drugs because each of them have their indication. Health authorities
      have implemented measures intended more to achieve savings than to improve
      prescriptions. There are not any studies which demonstrate that the second type
      of measures are more efficient than first one. AIM: To realize an economic
      evaluation, of a program of blood hypertension treatment taking and not taking
      into account the The Joint National Commission on Hypertension 6th Report.
      METHODS: Descriptive, prescription-indication study. Cost minimization. Health
      center from Valencia (Spain). Three hundred and thirteen patients were studied,
      randomly selected. Three strategy of cost decrease were considered: a) same
      prescription profile using the cheapest drugs, b) change of profile taken into
      account JNC-VI recommendations using the original drugs, and c) second option,
      but using the cheapest drugs. RESULTS: Ninety seven percent of diuretics had
      specific indications, 84% of beta blockers, 64.5% of IECAS, 31.6% of alfa
      blockers and 13% de calcium channel blockers. Diuretics were counter-indicated in
      3.5% of patients, beta blockers in 10.5%, and both in 3.1%. Total cost of the
      unmodifed prescription was 12.412.839 pesetas, cost of the first strategy was
      10.067.107, of the second 5.311.783 pesetas and of the third 1.999.094 pesetas.
      CONCLUSIONS: Our prescription profile don't follow JNC VI recommendations and
      this is not justified on indications or counterindications of diuretics and beta
      blockers. Following JNC VI is more efficient than looking only for the cheapest
      drug.

PMID- 11578563
TI  - [Meningococcal disease in Spain: seasonal nature and recent changes].
AB  - BACKGROUND: In this study we built a time series model in the time domain based
      on the cases of meningococcal disease declared every four weeks in Spain between
      1972 and 1998 With the model we analyzed the incidence of the disease and
      examined whether an epidemic really took place at the beginning of 1997, or
      whether the values were in the range of expectations. At this time there was
      widespread social alarm in Spain, because there was considered to be an outbreak
      of meningitis. We also examined whether the incidence of the disease diminished
      during 1997 following the measures introduced by the Comision Interterritorial
      del Sistema Nacional de Salud. METHOD: The data on the incidence of the
      meningococcal disease in Spain were obtained from the Boletin Epidemiologico
      Semanal, published by the Instituto de Salud Carlos III, declared from 1972 to
      1998 and grouped every four weeks. The method corresponds to the time series
      model in the domain of time: the Box-Jenkins method. RESULTS: In order to explain
      the behaviour of the disease during the years of the study we chose a model
      ARIMA(0,1,1) (0,1,1)13 that shows annual seasonal behaviour, with higher
      incidence in the winter and the beginning of spring, and lower incidence in
      summer. An intervention analysis showed that in March 1996 there was a level
      shift in the incidence of the illness. This lasted until September 1997, at which
      time the incidence returned to pre-1996. CONCLUSIONS: The measures of sanitary
      monitoring against the meningitis in the months of greater incidence, winter and
      beginning of spring must be intensified. Between spring 1996 and autumn 1997 the
      incidence of meningitis increased. Thereafter, until the end of 1998, there was a
      significant decrease in incidence, attributable to the performance of the health
      authorities.

PMID- 11578564
TI  - [The Bayesian approach: another way of drawing inferences].
AB  - The serious objections made with regard to significance tests account for the
      necessity of employing another inferential procedure. Bayesian methods are free
      of such objections, and they provide a very attractive alternative. By means of a
      simple example, this article illustrates how a typical problem of medical
      research could be solved using these two approaches. Bayesian methods offer more
      information and are more useful than conventional ones for analyzing experimental
      outcomes. In addition, a natural interpretation of conclusions are given by
      Bayesian methods. Finally, modern computational programs allow us to solve their
      complex calculation.

PMID- 11578565
TI  - [The problem of repeated measurements. Longitudinal analysis in epidemiology].
AB  - In longitudinal analyses subjects are repeatedly measured along time. They are
      mixed designs, characterised for their simultaneous consideration of two or more
      dimensions of analysis, in which time is one of the dimensions.Longitudinal
      analyses have important advantages with respect other designs. The most important
      is that they are more efficient, since they allow to distinguish between
      individual and within-individual variation.Longitudinal analyses can be
      approached marginal and conditionally. Whereas the former allows to draw
      poblational, or average, inferences, the latter permits to draw individual
      inferences.The statistical models to use depend on the type of response variable.
      If the dependent variable is normally distributed one will use linear mixed
      models. When the response is a count one will use mixed Poisson regressions.
      Mixed binomial or multinomial logistic regressions should be used when the
      response would be categorical.

PMID- 11578566
TI  - [Community collection of syringes by parenteral drug users complementary to
      syringe exchange programs].
AB  - OBJECTIVES: To contribute to harm reduction in injecting drug users (IDUs) by the
      implementation of a programme to withdraw abandoned syringes from public places,
      as well as to collaborate on the social reinsertion of IDUs. METHODS: Descriptive
      study of the Syringe Withdrawal Community (RECOJE in Spanish), carried out from
      1997 to 1999 by IDUs, the We Are Helpful Association (ASUT in Spanish) and the
      Social and Health Prevention and Attention Service (SAPS in Spanish) of the Red
      Cross, in Ciutat Vella (Barcelona, Spain). RESULTS: 4,332 syringes were
      withdrawn, 849 in 1997, 1,324 in 1998 and 2,159 in 1999. The mean number of
      syringes withdrawn each time was 57 33. 45 different IDUs worked in RECOJE. 74.2%
      of the abandoned syringes were found in parks, gardens, car parks and open
      spaces. CONCLUSIONS: RECOJE can be a valid programme for harm reduction
      complementary to the exchange syringe programmes. It could improve the self
      esteem, external image and organization of IDUs, contributing to their social
      reinsertion.

PMID- 11578567
TI  - [Health intervention in an Albanian-Kosovar refugees camp].
AB  - This paper focuses on the health intervention developed in a camp of Albanian
      Kosovar refugees, displaced as a consequence of the Balcans war in Kosova.
      Between May and June 1999, the camp of Kavaje in Albania, received 1,700
      refugees, with an average age of 24 years old. During this period, 1904 cases
      were registered at the primary health care centre settled in the camp. The most
      frequent causes of consultation were respiratory infections (22%), external
      causes (21%), skin infections and intestinal diseases (12%). A part of the
      psychological damage, the population attended didn't present with relevant health
      problems. Most of the visits to the doctor, related to the difficulties suffered
      on their way to the camp and to the conditions they were living on.

PMID- 11578568
TI  - [The Internet and the reports of the medical technology evaluation agencies].

PMID- 11578573
TI  - [Obtaining educational level through a survey of relatives of the deceased. Are
      responses reliable?].

PMID- 11578576
TI  - [Continuing education in PET].

PMID- 11578574
TI  - [A new health strategy for Europe].

PMID- 11578578
TI  - [Brain SPECT with 201-thallium in AIDS patients].
AB  - Brain lymphoma is a late complication in AIDS. Lymphoma incidence is increasing
      in AIDS patients due to the introduction of HAART and prolongation of these
      patients' life expectancy. This work aims to evaluate the usefulness of brain
      SPECT with 201Tl in patients with AIDS who present focal brain lesions in
      computed tomography (CT). METHODS: Seventeen patients with neurologic symptoms
      and focal neurologic lesions in the CNS (central nervous system) were studied.
      The images were interpreted as positive when the intensity of the focal deposit
      of the tracer was greater than that of the adjacent tissue. The SPECT results
      were compared with serologic data, clinical evolution and/or radiologic follow-up
      and cerebral biopsy. RESULTS: SPECT images showed focal uptake of radiotracer in
      3 patients. All three died shortly after the SPECT was performed. All of them had
      negative serology for toxoplasmosis. Four patients were diagnosed of progressive
      multifocal leukoencephalopathy and the ten remaining cases had a good clinical
      and/or radiologic response. CONCLUSIONS: Brain SPECT with 201Tl is a very useful
      non-invasive technique for the differential diagnosis of cerebral focal lesions
      in AIDS patients.

PMID- 11578577
TI  - [Bronchial carcinoid tumor and scintigraphy of somatostatin receptors: detection
      of bone metastasis].
AB  - Surgery is the treatment of choice for bronchial carcinoid tumor (BCT), whenever
      the staging is adequate. There is little information about the capability of the
      somatostatin receptor scintigraphy (SRS) to detect bone metastases in the
      carcinoid tumor. AIM: This work has aimed to evaluate retrospectively the
      diagnostic accuracy of the SRS in the detection of bone metastases in BCT.
      MATERIALS AND METHODS: Based on their clinical indication, the patients were
      classified into two different groups: Group A (n = 4), staging of a known BCT;
      and Group B (n = 6), treatment control. The SRS results could be correlated with
      the CT results in all 4 patients from the group A, and in one patient from the
      group B, and the SRS results were compared with the clinical follow up during at
      least one year in the other 5 patients. RESULTS: The SRS scan detected the 4 BCT
      from the group A; in 2 of them the patient staging was superior when the SRS was
      used than with the CT, whereas the scan overestimated the tumor stage (BCT +
      sarcoidosis) in another patient. During the clinical course, one of these
      patients developed bone and liver metastases. The SRS was normal in 5
      asymptomatic patients from group B, whereas the scan showed disseminated
      metastatic disease (liver, bone, spleen and lymph nodes) in another patient. In
      the 2 patients with bone metastases, the total number of bone metastases detected
      by the bone scan was 12, and by the SRS 8. The four lesions that were not
      detected by SRS were located in the ribs (n = 3) and 12-D (n = 1). CONCLUSIONS:
      The capability of the SRS to detect bone metastases makes it more useful in BCT
      staging. Over the next few years, the role of the bone scan and SRS in the
      detection of bone metastases in carcinoid tumors needs to be established.

PMID- 11578579
TI  - [Prognostic value of myocardial perfusion SPECT in multivessel coronary disease
      patients with left ventricular dysfunction, comparing revascularized and non
      revascularized patients].
AB  - OBJECTIVE: We investigated the prognostic value of 99mTc-Tetrofosmin myocardial
      SPECT (99mTc-TF) in dysfunctional multivessel coronary disease patients who
      underwent revascularization (RV) or only medical treatment (MT). METHODS: In 78
      coronary patients with 2-3 diseased vessels and left ventricular ejection
      fraction (EF) <= 40% (24 10%), we have assessed the extension of the stress
      perfusion defect, and percent of reversibility (R) by quantification of stress
      rest myocardial SPECT 99mTc-TF bull's eyes (2 days-protocol), lung/heart ratio
      (LH) calculated in the original stress SPECT images, and EF by equilibrium
      radionuclide ventriculography obtained at 24 h. A R value >= 8% was used to
      identify viable (V) patients. A total of 28 patients underwent RV and 50 only
      received MT. After a mean follow-up of 22.9 20 months (3-60), they were
      considered as coronary events (CE): cardiac death, non-fatal infarction and heart
      transplant. CE rate was 20.5% (16/78). RESULTS: No significant differences were
      found in the pre-revascularization study characteristics, except a significantly
      higher mean R value in RV (10.6 9.5%) than in MT patients (6.4 7.8%) p: 0.03, and
      the main difference was that RV patients showed less CE 2/28 (7%) than the MT
      group 14/50 (28%) p: 0.02. The CE rate was lower in V patients who underwent RV
      (6%) than in V patients with MT (45%) p: 0.03, but no significant difference was
      obtained in non-V patients between RV (7%) and MT (16%) groups. In viable
      patients, the corresponding survival curves (Kaplan-Meier) showed a CE-free
      survival at 5 years of 79% in patients RV and of 42% in MT patients, p: 0.03,
      without significant difference in non-V patients. CONCLUSIONS: Patients with
      viable myocardium by myocardial SPECT have a good prognosis after
      revascularization, and show higher risk of CE if they are only medically treated.
      Myocardial viability is an indispensable assessment in prognosis evaluation and,
      above all, in therapeutic decision making in dysfunctional multivessel coronary
      disease patients.

PMID- 11578581
TI  - [Thyroid scintigraphy and body scanning with 67 Ga in a case of primary thyroid
      lymphoma].
AB  - The case of a 60-year old woman first presented a rapidly growing left cervical
      mass is presented. The fine needle aspiration-puncture (FNAP) lead to a diagnosis
      of thyroiditis. Due to the persistence of the symptoms, the FNAP was repeated
      again but was not conclusive, so that a surgical biopsy was performed. The
      pathological diagnosis was diffuse large cell primary thyroid lymphoma (PTL). The
      PTL is a rare entity that accounts for less than 1% of all the Non-Hodgkin's
      lymphomas. The thyroid scintigraphy showed the existence of a cold nodule in the
      left thyroid lobule and the 67Ga scan revealed a large abnormal lesion in the
      mediastinum that extended to the right latero-cervical region. After two
      chemotherapy courses, the 67Ga scan was normal.

PMID- 11578580
TI  - [Study of renal transplant by deconvoluted renogram with 99m Tc
      mercaptoacetyltriglycine (Mag3)].
AB  - AIM: To evaluate the usefulness of the 99mTc-MAG3 renogram deconvolution and its
      derived parameters in kidney graft function monitoring. MATERIAL AND METHOD: 221
      renograms were studied: 64 were diagnosed as functioning graft (FG), 37 as
      functioning graft with elevated serum creatinine (FG2), 59 as acute tubular
      necrosis (ATN), 30 as acute rejection (AR), 20 as urinary tract obstruction (OBS)
      and 11 as cyclosporine nephrotoxicity (TNX). The parameters evaluated were:
      maximal activity of conventional renogram and mean transit time (MTT), time to
      reach 20% (T20) and 80% (T80) of the height of the RRF and initial uptake (IU)
      from the deconvoluted renal retention function (RRF). RESULTS: MTT and T20 were
      significantly longer and IU significantly lower in non-functioning grafts.
      However, MTT and T20 became shorter than in FG when graft function is severely
      impaired. CONCLUSION: IU, MTT and T20 are more useful than maxim activity of
      renogram in monitoring kidney graft function and in evaluating renal dysfunction
      severity. IU is a very sensitive and early parameter.

PMID- 11578582
TI  - [Calculation of the blood volume with isotopic dilution. Theoretical and
      practical review].

PMID- 11578583
TI  - [Uptake of anti-CEA monoclonal antibody labeled with 99mTc in a patient with
      Paget's disease during a study of sigmoid cancer relapse].

PMID- 11578584
TI  - [Photopenic lesions with 99mTc-HMPAO-leukocytes in vertebral osteomyelitis].

PMID- 11578585
TI  - [PET radiopharmaceuticals].

PMID- 11578586
TI  - [Clinical-biological characteristics of infiltrating ductal carcinomas of the
      breast with estrogen receptor concentrations >300 fmol/mg protein].

PMID- 11578592
TI  - Expressions of neuropilin-1, neuropilin-2 and semaphorin 3A mRNA in the rat brain
      after middle cerebral artery occlusion.
AB  - This study investigated the spatial and temporal expressions of mRNA encoding
      neuropilin (Npn)-1, Npn-2 and semaphorin3A (Sema3A) in the rat brain after
      occlusion of the middle cerebral artery (MAC) distal to the striate branches. The
      expression of Npn-1 mRNA was transiently upregulated in layers V and VI of the
      parietal cortex not entering infarction on the lesion side from 3 to 6 h after
      MCA occlusion. The transient up-regulation of Npn-1 mRNA expression was
      presumably accompanied by an increase in Npn-1 protein as shown by
      immunohistochemistry in combination with in situ hybridization histochemistry.
      Intense Npn-2 mRNA expression was noted temporarily in layer II of the parietal
      cortex on the lesion side from 1 to 6 h after MCA occlusion. The expression of
      Sema3A mRNA was upregulated in layer VI of the non-infarcted parietal cortex on
      the lesion side at 6 h after MCA occlusion. The above increases in mRNA
      expression were no longer observed at 12 h after MCA occlusion. The expressions
      of Npn-1, -2 and Sema3A mRNA were not detected in the ventroposterior thalamic
      nucleus undergoing secondary degeneration after MCA occlusion. In the infarct
      lesion or ischemic core, neuronal expressions of Npn-1, -2 and Sema3A disappeared
      by 3 days after MCA occlusion as the neurons in situ entered apoptosis or
      necrosis. In contrast, ED-1-positive microglia/macrophages with Npn-1 and Npn-2
      mRNA were observed in the infarct lesion at 1 week after MCA occlusion. These
      findings suggest that the temporal up-regulation of Npn-1 and Sema 3A mRNA
      expressions in the non-infarcted parietal cortex on the lesion side is
      insufficient to induce neuronal cell death possibly because the up-regulated mRNA
      molecules are not fully translated and that the overexpression of Npn-1 and/or
      Npn-2 in the ischemic core with degenerating neurons enables activated microglial
      cells to contact the damaged neurons in situ for phagocytosis.

PMID- 11578593
TI  - Analysis of genes differentially expressed in astrocytes stimulated with
      lipopolysaccharide using cDNA arrays.
AB  - We used cDNA arrays to investigate differentially expressed genes in astrocytes
      challenged with lipopolysaccharide (LPS). Astrocyte cultures were prepared from 1
      day-old rat brains. Purified astrocytes were treated with LPS (1 microg/ml) for
      2, 8 and 48 h. Differentially expressed genes in these astrocytes were examined
      with Atlas rat cDNA arrays. At all the three time points studied, three genes
      were found consistently up-regulated: I-kappaB alpha chain, NF-kappaB, and
      interferon induced protein. In addition to these three, six other genes were also
      up-regulated at 2 and 8 h. They were genes encoding vascular cell adhesion
      protein 1 (VCAM-1), interferon regulatory factor 1 (IRF-1), mitochondrial
      hydroxymethylglutaryl-CoA synthase (HMG-CoA synthase), aldehyde dehydrogenase 2,
      macrophage inflammatory protein 1 (MIP-1) and neurotensin receptor 2. At these
      two time points, three genes were down-regulated: copper-zinc-containing
      superoxide dismutase 1 (SOD-1), insulin-like growth factor binding protein 1
      (IGFBP-1), and insulin-like growth factor binding protein 3 (IGFBP-3). Expression
      of several differentially expressed genes in cDNA array (I-kappaB, VCAM-1 and MIP
      3) were further confirmed by reverse transcription polymerase chain reaction
      study. The prominently modulated genes could be classified into three categories:
      nuclear transcription factors, pro-inflammatory cytokines/chemokines and
      metabolic enzymes. Application of pyrrolidine dithiocarbamate, an inhibitor of
      nuclear factor-kB (NF-kappaB), prior to LPS stimulation not only prevented up
      regulation of NF-kappaB gene expression, but also completely blocked up
      regulation of pro-inflammatory cytokine genes (TNF-alpha and interleukin-1beta)
      and two chemokine genes: CXC chemokine LIX and CC chemokine MIP-3 alpha. These
      results indicate that both up-regulation of inflammatory cytokine expression and
      down-regulation of growth factor expression are probably involved in the response
      of astrocytes upon exposure to LPS.

PMID- 11578594
TI  - Axon terminals containing tyrosine hydroxylase- and dopamine-beta-hydroxylase
      immunoreactivity form synapses with galanin immunoreactive neurons in the lateral
      division of the bed nucleus of the stria terminalis in the rat.
AB  - Catecholaminergic projections from brainstem sources to the bed nucleus of the
      stria terminalis play a central role in the neurochemically mediated
      modulation/regulation of stress response. The lateral division of the bed nucleus
      of the stria terminalis (BSTL) exhibits several galanin immunoreactive (ir)
      neurons that are also central in the modulatory control of acute stress
      responses. The distribution of galaninergic nervous structures overlaps with that
      of the dopaminergic and noradrenergic axon terminals in the BSTL. Since both
      monoamines and galanin regulate/modulate the central regulatory pathways of
      endocrine, behavioral and physiological responses during stress, the aim of this
      study was to demonstrate synaptic interaction between galanin-ir nervous
      structures and fiber terminals immunopositive for dopamine or noradrenaline in
      the BSTL, thereby providing morphological data to understand better the
      significance of catecholamine-galanin interactions in brain areas responding to
      stressful stimuli. Double-labeling immunohistochemistry applied both at light and
      electron microscopic levels made it possible to demonstrate synaptic interactions
      between galanin-ir nervous structures and axon terminals immunopositive for
      either dopamine or noradrenaline. The dopaminergic fiber terminals innervated
      galanin-ir cells and dendrites in the laterodorsal division of the bed nucleus of
      the stria terminalis (BST), whereas the noradrenergic axons contacted
      galaninergic neurons and dendrites in the lateroventral BST. In this study,
      interactions between monoamines and galanin-ir structures were demonstrated in
      the BSTL which can be central in the modulatory control of the major stress
      regulatory pathway of the limbic-hypothalamo-pituitary-adrenal axis.

PMID- 11578595
TI  - Glutamic acid decarboxylase-immunoreactivity of bulbar respiratory neurons
      identified by intracellular recording and labeling in rats.
AB  - To distinguish the GABAergic neuron in the ventral respiratory group (VRG) of
      rats, immunohistochemical staining of glutamic acid decarboxylase (GAD) was
      performed in neurons that had been individually identified by in vivo
      intracellular recording and labeling with neurobiotin. A total of five types of
      respiratory neurons were identified and labeled; augmenting inspiratory (aug-I,
      n=12), decrementing or early inspiratory (early-I, n=3), inspiration-expiration
      phase spanning or late inspiratory (late-I, n=3), decrementing expiratory or
      postinspiratory (PI, n=8), and augmenting or stage 2 expiratory (E2, n=3). In
      addition, expiration-inspiration phase-spanning or pre-inspiratory neurons (pre
      I, n=2) were recorded, but not labeled. The membrane potential trajectory of each
      neuron type resembled that previously described in cat, suggesting a comparable
      neuronal organization between the two species. According to the axonal
      arborization, those labeled neurons were further classified as propriobulbar (6
      aug-I, all early-I, all late-I, and 3 PI), bulbospinal (2 aug-I and all E2) and
      cranial-motor neurons (4 aug-I and 5 PI). GAD-immunoreactivity was consistently
      detected in the propriobulbar neurons, while it was not seen in cranial-motor and
      bulbospinal neurons. In addition, GAD-immunoreactive varicosities were found
      surrounding the somatic and dendritic surface of all labeled neurons. The present
      results illustrate that the propriobulbar types of early-I, aug-I, late-I and PI
      neurons are GABAergic inhibitory neurons and virtually all types of respiratory
      neurons receive GABAergic inputs in the rat's VRG.

PMID- 11578596
TI  - Altered expression of the synuclein family mRNA in Lewy body and Alzheimer's
      disease.
AB  - The main objective of this study was to determine if levels of alpha-, beta-
      and/or gamma-synuclein mRNAs are differentially affected in brains of Lewy body
      disease (LBD) and Alzheimer's disease (AD) patients, compared to controls. In
      control cases, highest levels of expression were observed in the neocortex and
      the lowest in basal ganglia and substantia nigra. beta-Synuclein was the most
      abundant message (75-80%), followed by gamma-synuclein (10-15%) and alpha
      synuclein (8-10%). Analysis of the superior temporal cortex, a region selectively
      affected in LBD and AD, showed that compared to controls, levels of alpha
      synuclein were increased in cases of diffuse LBD (DLBD), levels of beta-synuclein
      were decreased in AD and DLBD, and levels of gamma-synuclein were increased in AD
      cases. This study suggests that a critical balance among products of the
      synuclein gene is important to maintain normal brain function and that
      alterations in this balance might be associated with neurodegenerative disorders.

PMID- 11578597
TI  - Function of SERCA mediated calcium uptake and expression of SERCA3 in cerebral
      cortex from young and old rats.
AB  - Previous work on peripheral sympathetic neurons indicated that a decline in
      sarco/endoplasmic reticulum calcium ATPase (SERCA) function occurs with advancing
      age. Therefore, an age-related decline in mechanisms controlling intracellular
      calcium homeostasis could contribute to altered neuronal function and/or
      degeneration. In this study we sought to extend the findings on peripheral
      neurons and to detect possible age-related declines in SERCA function and
      expression of SERCA3 in central neurons from cerebral cortex from young (6-month)
      and old (20-month) rats. Functional studies compared ATP-dependent 45Ca(2+)
      uptake into microsomes and plasma membrane vesicles (PMVs). We and found no
      significant difference in 45Ca(2+)-uptake between microsomes or PMVs between
      young and old animals. On the other hand expression of SERCA3 mRNA in rat
      cerebral cortex showed a significant decline with advancing age. However,
      comparison of SERCA3 protein content did not reveal a corresponding decline;
      implying that SERCA mRNA turnover rates may be greater in the younger group.
      Although the present work with rat cerebral cortex does not indicate an age
      related decline in SERCA function, previous work from our laboratory on
      sympathetic nerves and by others on the hippocampus indicate such a decline. In
      light of our previous and current studies, aging may affect calcium homeostatic
      mechanisms in central and peripheral autonomic neurons differently.

PMID- 11578598
TI  - In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70
      can enhance neuronal stress tolerance.
AB  - Glial cells release a variety of molecules that support neuronal function.
      Because heat shock proteins (Hsps) are important in the survival of neurons
      subjected to metabolic stress, the possibility that glia can release the
      inducible form of the 70 kDa Hsp (Hsp70) was examined. Additionally, the ability
      of neuronal cells to show increased stress tolerance by taking up a mixture of
      constitutive and inducible forms of Hsp70 (Hsc/Hsp70) added to the extracellular
      fluid was tested. Human T98G glioma cells and differentiated LA-N-5 neuroblastoma
      cells were used as model glia and neurons to investigate these points. Hsp70 was
      analyzed using affinity chromatography, Western blotting, and immunofluorescence
      microscopy. The glioma cells were shown to export Hsp70 into the culture medium
      whether under normal conditions or subjected to heat shock. The amount of glial
      Hsp70 released ranged from 5 to 15 pg per 10(6) cells per day, being greater
      following heat shock. Neuroblastoma cells took up biotinylated Hsc/Hsp70 within 1
      h after it was added to the culture medium and it made them more resistant to
      heat shock (44 degrees C) and to staurosporine-induced apoptosis. This increased
      stress tolerance was especially important in neuroblastoma cells induced to
      differentiate with phorbol ester because those 'mature neurons' showed a 10-fold
      decline in endogenous Hsp70, which was accompanied by increased susceptibility to
      heat shock and staurosporine-induced apoptosis. These results suggest that
      extracellular Hsp70 may provide a means by which glia can affect neuronal
      function, perhaps enhancing neuronal stress tolerance.

PMID- 11578599
TI  - The effects of endomorphin-1 on conditioned defeat in Syrian hamsters
      (Mesocricetus auratus).
AB  - The present study examined the effect of endomorphin-1 (EM1), an endogenous
      opioid with a high affinity for the mu opiate receptor, on conditioned defeat.
      Conditioned defeat is a phenomenon in which hamsters that have been defeated
      subsequently fail to exhibit normal territorial aggression and instead display
      submissive/defensive behaviors even when paired with a non-aggressive intruder.
      In experiment 1, animals were placed in the home cage of a larger resident for 15
      min and were defeated. After 24 h, animals received a 3-microl injection of EM1
      (0.0, 0.3, 3.0, or 10 nmol) into the left lateral cerebral ventricle 5 min before
      a smaller non-aggressive intruder was placed in the home cage of the experimental
      animal. In experiment 2, animals were infused with EM1 immediately after the
      initial defeat and were paired with a non-aggressive intruder 24 h later as in
      experiment 1. EM1 reduced the duration of submissive/defensive behavior in
      experiment 1 (P<0.05) but not in experiment 2 (P>0.05). These data support the
      hypothesis that the highly selective mu receptor agonist endomorphin-1 modulates
      the expression of conditioned defeat, but provides no support for the hypothesis
      that endomorphin-1 modulates the consolidation of conditioned defeat.

PMID- 11578600
TI  - Decrease in GABA synthesis rate in rat cortex following GABA-transaminase
      inhibition correlates with the decrease in GAD(67) protein.
AB  - gamma-Aminobutyric acid (GABA) synthesis in the brain is mediated by two major
      isoforms of glutamic acid decarboxylase, GAD(65) and GAD(67). The contribution of
      these isoforms to GABA synthesis flux (V(GAD)) is not known quantitatively. In
      the present study we compared V(GAD) in cortex of control and vigabatrin-treated
      rats under alpha-chloralose/70% nitrous oxide anesthesia, with total GAD activity
      and GAD isoform composition (GAD(65) and GAD(67)) measured by enzymatic assay and
      quantitative immunoblotting. V(GAD) was determined by re-analysis of 13C NMR data
      obtained ex vivo and in vivo during infusions of [1-13C]glucose using an
      extension of a model of glutamate-glutamine cycling that included a discrete
      GABAergic neuronal compartment with relevant interconnecting fluxes. V(GAD) was
      significantly lower in vigabatrin-treated rats (0.030-0.05 micromol/min per g,
      P<0.003) compared to the non-treated control group (0.10-0.15 micromol/min per
      g). The 67-70% decrease in V(GAD) was associated with a 13% decrease in total GAD
      activity (P=0.01) and a selective 44+/-15% decrease in GAD(67) protein (from
      0.63+/-0.10 to 0.35+/-0.08 microg protein/mg tissue, P<0.05); GAD(65) protein was
      unchanged. The reduction in GAD(67) protein could account for a maximum of
      approximately 65% of the decrease in V(GAD) in vigabatrin-treated animals
      suggesting that inhibition of GAD(65) must have also occurred in these
      experiments, although product inhibition of GAD(67) by increased GABA could play
      a role. GAD(67) could account for 56-85% of cortical GABA synthesis flux under
      basal conditions and the entire flux after vigabatrin treatment.

PMID- 11578601
TI  - Altered sexually dimorphic nucleus of the preoptic area (SDN-POA) volume in adult
      Long-Evans rats by dietary soy phytoestrogens.
AB  - Naturally occurring estrogen-like molecules in plants (phytoestrogens), present
      via soy, in animal diets can alter morphology and physiology in rodents.
      Phytoestrogens have the ability to bind estrogen receptors and exert many of the
      biological responses evoked by physiological estrogens. This study characterized
      the effects of dietary phytoestrogens on the expression of body and prostate
      weight, circulating testosterone and estradiol levels, puberty onset, vaginal
      cyclicity, and volume of the sexually dimorphic nucleus of the preoptic area (SDN
      POA) in Long-Evans rats. Using different experimental protocols, animals were fed
      either a phytoestrogen-rich (Phyto-600) or a phytoestrogen-free (Phyto-free)
      diet. Animals fed the Phyto-600 diet displayed significantly decreased body
      weights (in males and females), prostate weights and delayed puberty in females
      compared to that of animals fed the Phyto-free diet. Circulating testosterone or
      estradiol levels in males or estrous cyclicity were not altered by the diets. The
      volume of the SDN-POA was significantly altered by a change in diet at 80 days of
      age where one-half of the males or females fed the Phyto-600 diet (from birth)
      were switched to the Phyto-free diet until 120 days of age. Males initially fed a
      Phyto-600 diet but changed to a Phyto-free diet had significantly smaller SDN-POA
      volumes compared to males fed the Phyto-600 diet (long-term). These data suggest
      that consumption of phytoestrogens via a soy diet, significantly: (1) decreases
      body and prostate weight, (2) delays puberty onset, and (3) alters SDN-POA
      volumes during adulthood.

PMID- 11578602
TI  - Medio-lateral balance adjustments preceding reflexive limb withdrawal are
      modified by postural demands.
AB  - We have recently observed medio-lateral balance adjustments (BA) preceding
      reflexive stepping elicited by noxious stimulation. While task specific
      modulation is evident for BA prior to voluntary leg movement, it is unclear
      whether rapid BA reactions (prior to 'reflexive' stepping) represent a generic
      response to evoked limb withdrawal or can be modified to suit task-conditions.
      This study was designed to establish whether the CNS is able to modify rapid
      onset latency BAs to match task conditions. Reflexive stepping was evoked by
      applying a noxious stimulus (50 ms stimulus train, 1 ms pulses, 300 Hz, 4 x
      perceptual threshold) to the plantar surface of the either the left or right
      foot. Task conditions were varied prior to stimulation by having subjects
      maintain one of three different static positions: (1) lean left (70% body weight
      (BW) on left), (2) neutral (50% BW both sides), (3) lean right (70% BW on right).
      BAs were denoted by centre-of-pressure (CoP) excursions towards the swing foot
      after the onset of noxious stimulation (average onset latency of 128 ms). There
      was a significant increase in frequency of occurrence and a significant increase
      in magnitude of CoP shift when the stimulation was applied to a loaded limb
      (leaning with 70% BW on the stimulated foot) as compared to an unloaded limb (30%
      BW). In addition, 78% of loaded trials featured steps taken with the unstimulated
      foot, which delayed removal of the stimulated foot. Collectively, the results
      indicate modifiability of the very rapid onset balance adjustments that precede
      the onset of limb withdrawal revealing complex control of balance exists even
      over very brief latencies.

PMID- 11578603
TI  - Temporal and spatial distribution of Fos protein in the lumbar spinal dorsal horn
      neurons in the rat with chronic constriction injury to the sciatic nerve.
AB  - The temporal and spatial expression pattern of Fos protein in spinal dorsal horn
      neurons was examined by immunohistochemistry in rats with chronic constriction
      injury (CCI) to the sciatic nerve. In normal animals, a few Fos-immunoreactive (
      IR) neurons were detected in the dorsal horn of the lumbar spinal cord. Following
      induction of CCI, a very large number of Fos-IR neurons appeared in the spinal
      dorsal horn, but a significant number of Fos-IR neurons were also observed in the
      contralateral dorsal horn where primary afferents of the injured sciatic nerve
      rarely project. Sham-operated animals also had a significant number of Fos-IR
      neurons in the dorsal horn bilaterally. The number of Fos-IR neurons reached its
      maximal level 1 day following placement of the ligatures (PO 1d). The ratio of
      the number of Fos-IR neurons in the ipsilateral dorsal horn to the contralateral
      dorsal horn, however, had its peak level 3 days following CCI (3.1-fold increase
      compared to the contralateral dorsal horn). The number of Fos-IR neurons in the
      dorsal horn gradually decreased, but increased again around PO 15d. On PO 30d,
      the number of Fos-IR neurons decreased and became comparable to that in normal
      animals. The present results indicate that the induction of Fos-IR neurons in the
      dorsal horn caused by CCI is biphasic and reaches its maximal level on PO 3d,
      near the time of hyperalgesia onset.

PMID- 11578604
TI  - Stimulatory effects of centrally injected kainate and N-methyl-D-aspartate on
      gastric acid secretion in anesthetized rats.
AB  - The effects of N-methyl-D-aspartate (NMDA), kainate and (+/-)-alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionate (AMPA), ionotropic glutamate agonists, on
      gastric acid secretion were investigated in the continuously perfused stomach of
      anesthetized rats. The lateral ventricular (LV) injection of kainate (0.01-1
      microg) or NMDA (0.3-3 microg) dose-dependently stimulated gastric acid
      secretion. AMPA (3-10 microg) also stimulated gastric acid secretion but the
      effect was very weak. Repeated injections of kainate (0.1 microg) or NMDA (1
      microg), at least twice, stimulated gastric acid secretion to a similar degree.
      The effect of kainate (0.1 microg) was blocked by the kainate receptor
      antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione disodium (3 microg, LV) and D
      gamma-glutamylaminomethanesulfonic acid (30 microg, LV), but not by NMDA receptor
      antagonists. The effect of NMDA (10 microg) was blocked by (+/-)-3-(2
      carboxypiperazin-4-yl)-1-propylphosphonic acid (10 microg, LV), a competitive
      NMDA receptor antagonist, and (+)-5-methyl-10,11-dihydro-5H-dibenzocyclo-hepten
      5,10-imine hydrogen maleate (10 microg, LV), a non-competitive NMDA receptor
      antagonist, but not by kainate receptor antagonists. Moreover, the gastric acid
      secretion stimulated by kainate and NMDA were completely blocked by systemic
      atropine injection (1 mg/kg, i.v.) and vagotomy. These findings suggest that
      kainate and NMDA receptor mechanisms are independently involved in the central
      nervous system to control gastric acid secretion through vagus cholinergic
      activation.

PMID- 11578605
TI  - Differential expression of protein kinase C betaI (PKCbetaI) but not PKCalpha and
      PKCbetaII in the suprachiasmatic nucleus of selected house mouse lines, and the
      relationship to arginine-vasopressin.
AB  - The functional significance of the suprachiasmatic nucleus (SCN) in circadian
      rhythm control of mammals has been well documented. The role of protein
      phosphorylation mediated by protein kinase C (PKC), however, is not well known.
      We report the immunocytochemical localization of three Ca(2+)-dependent PKC
      isoforms (alpha, betaI, betaII) within the SCN of selected house mouse lines that
      differ in behavioral circadian rhythm parameters. Optical density measurements
      revealed that the adult mice selected for low levels of nest-building behavior
      (small nest-builders) had more than threefold higher PKCbetaI immunostaining in
      the SCN than the mice selected for high levels of nest-building behavior (big
      nest-builders). A similar twofold difference between the adult small and big nest
      builders was observed for the number of PKCbetaI-containing cells in the SCN. The
      non-selected control lines were intermediate. Ten-day-old pups revealed similar
      differences in PKCbetaI immunostaining in the SCN between the small and big nest
      builders. PKCalpha and PKCbetaII immunostaining in the SCN was not different
      among the lines. PKCbetaI immunostaining was not different among the selected
      lines in the lateroanterior hypothalamic nucleus (LA) and the cornu ammonis field
      1 (CA1) of the dorsal hippocampus and confirms the specificity of the difference
      in PKCbetaI immunostaining in the SCN among the selected lines. The significance
      of these findings is discussed in the context of differences among the lines in
      arginine-vasopressin (AVP) and light-induced Fos expression in the SCN,
      behavioral phase-delay responses to 15-min light pulses in constant darkness, and
      measures of the strength of the circadian activity rhythm expressed.

PMID- 11578606
TI  - Postsynaptic dorsal column and cuneate neurons in raccoon: comparison of response
      properties and cross-correlation analysis.
AB  - The responses of 111 postsynaptic dorsal column (PSDC) neurons in the cervical
      spinal cord and 51 cuneate neurons with receptive fields on the glabrous skin of
      the forepaw were studied in anesthetized raccoons using extracellular recording
      techniques. The PSDC neurons had larger receptive fields than the cuneate
      neurons, but in both groups the fields never extended onto hairy skin. PSDC and
      cuneate neurons had approximately the same mean latency to electrical stimulation
      of the receptive field, but PSDC neurons had significantly lower thresholds. The
      majority of both PSDC and cuneate neurons also responded to electrical
      stimulation of an adjacent digit, even though they did not respond to mechanical
      stimulation of that digit. Cross-correlation analysis of the activity of 51 pairs
      of PSDC and cuneate neurons recorded simultaneously revealed a significant
      interaction in 26 pairs during spontaneous activity. In 20 of these neuron pairs,
      the probability that the cuneate neuron would fire was greater after the PSDC
      neuron had fired (suggesting a spinocuneate interaction), five pairs showed an
      interaction in the opposite (cuneospinal) direction, and one pair had a
      significant inhibitory interaction. These interactions occurred more often when
      the receptive fields of the two neurons were overlapping than when their fields
      were on adjacent digits. Frequency response analysis revealed greater coherence
      for those pairs showing a spinocuneate interaction than for those with a
      cuneospinal interaction. These results support the hypothesis that the PSDC
      system exerts a tonic facilitatory effect on cuneate neurons and that there may
      be some somatotopic organization to the interactions. However, the similar
      response latencies of the two groups of neurons makes it unlikely that PSDC
      neurons could contribute to the rapid initial processing of cutaneous information
      by the cuneate nucleus.

PMID- 11578607
TI  - Evidence for involvement of the neural pathway containing the peripheral vagus
      nerve, medullary visceral zone and central amygdaloid nucleus in
      neuroimmunomodulation.
AB  - It is now evident that a bidirectional communication network exists between the
      central nervous system (CNS) and immune system (IS). However, the way in which
      the IS passes inform to the brain is not quite clear.In the present study, one of
      the neural pathways involved in the cytokine-to-brain communication was
      investigated in the rat. This pathway starts at the vagal nerve projecting to the
      medullary visceral zone (MVZ), an arc-shape band from the dorsomedial to
      ventrolateral area in the middle-caudal segment of the medulla oblongata, and
      terminates at the central amygdaloid nucleus (Ce) which receives projections from
      large catecholaminergic neurons in the MVZ. Animals were randomly divided into
      two experimental groups. Triple-labeling was used in Group I animals to combine
      wheat germ aggulutinin-conjugated horseradish peroxidase (WGA-HRP) retrograde
      tracing with anti-Fos and anti-tyrosine hydroxylase (TH) immunostaining. WGA-RP
      was stereotaxically injected into the unilateral Ce of the animals and, after a
      survival period of 48 h, intraperitoneal (IP) injection of lipopolysaccharide
      (LPS) was performed. Seven kinds of labeled neurons were observed in the MVZ,
      namely, HRP-, Fos- or TH-singly-labeled neurons; Fos/HRP-, Fos/TH- or HRP/TH
      doubly-labeled neurons; and Fos/HRP/TH-triply-labeled neurons. As for Group II
      animals, bilateral subdiaphragmatic vagotomy (SDV) or sham operation was
      performed, followed 4 weeks later by IP injection of LPS. The number of Fos
      positive neurons within the Ce and MVZ was significantly lower (P<0.01) in rats
      having SDV when compared with those receiving sham operation. Our results suggest
      that part of the peripheral immune information can be conveyed through the vagus
      to the catecholaminergic neurons in the MVZ, where it is transported to the Ce.
      The MVZ is a neural relay station in the immune-to-brain communication and might
      play a significant role in neuroimmuno-modulation via the vagus-MVZ-Ce pathway.

PMID- 11578608
TI  - Methylmercury inhibits cysteine uptake in cultured primary astrocytes, but not in
      neurons.
AB  - The maintenance of adequate intracellular glutathione (GSH) concentrations is
      dependent on the availability and transport of the rate-limiting substrate,
      cysteine. A suggested mechanism of methylmercury (MeHg) neurotoxicity in brain
      involves the formation of oxygen radicals, and a decrease in intracellular levels
      of GSH. Recently, we have characterized various cysteine transport systems (both
      Na(+)-dependent and -independent) in cerebrocortical astrocytes and hippocampal
      neurons. The present study was carried out to investigate the effect of MeHg on
      cysteine uptake in both astrocytes and neurons, and to determine whether cysteine
      transport is differentially affected in the two cell types by MeHg treatment.
      Sixty-minute pretreatment with MeHg caused significant concentration-dependent
      inhibition in cysteine uptake in astrocytes, but not in neurons. As most of the
      cysteine transport is Na(+)-dependent (80-90% of total), additional studies
      focused on MeHg's effect on the Na(+)-dependent cysteine transporters X(AG(-))
      and ASC. An additive inhibitory effect on cysteine uptake was observed in
      astrocytes treated with MeHg (5 microM) plus sub-maximal inhibitory
      concentrations (0.1 and 0.5 mM) of threo-beta-hydroxy-aspartate (THA), a specific
      inhibitor of the Na(+)-dependent transporter, X(AG(-)), compared to astrocytes
      treated with MeHg (P<0.001) or THA alone (P<0.05). There was no additive effect
      of MeHg and maximal inhibitory concentrations of THA (1.0 and 5.0 mM) on
      astrocytic cysteine uptake inhibition. Additional studies examined the
      sensitivity of the Na(+)-dependent ASC transport system to MeHg treatment.
      Maximal inhibitory concentration of L-serine (10 mM) alone had a rather modest
      inhibitory effect on cysteine uptake, and when applied in the presence of MeHg
      there was no additive effect. These results suggest that the inhibition of
      cysteine uptake by MeHg in astrocytes occurs through specific inhibition of both
      the X(AG(-)) as well as the ASC transport system.

PMID- 11578609
TI  - Fetal and adolescent nicotine administration: effects on CNS serotonergic
      systems.
AB  - Nicotine is a neuroteratogen that targets synaptic function during critical
      developmental stages and recent studies indicate that CNS vulnerability extends
      into adolescence, the time that smoking typically commences. We administered
      nicotine to pregnant or adolescent rats via continuous minipump infusions, using
      dose rates that replicate the plasma nicotine levels found in smokers. Fetal
      nicotine exposure (gestational days 4-21) decreased the cerebrocortical binding
      of paroxetine (PXT), a marker for the serotonin (5HT) transporter, likely
      indicative of a decrease in nerve terminals in that region; the effect lasted
      into adulthood. There was a corresponding increase in PXT binding in the
      midbrain/brainstem, the region containing the 5HT cell bodies that project to the
      cerebral cortex, a pattern typical of reactive sprouting in response to nerve
      terminal damage. After adolescent nicotine treatment (postnatal days 30-47), PXT
      binding was reduced in the hippocampus and striatum instead of the cerebral
      cortex, again accompanied by increased binding in the midbrain and brainstem; the
      patterns of effects within each region were gender-selective, although both males
      and females displayed abnormalities. Superimposed on this overall effect, there
      were transient increases in PXT binding, likely due to acute stimulant effects of
      nicotine. We also assessed 5HT presynaptic activity (5HIAA/5HT ratio). Withdrawal
      from adolescent nicotine treatment led to suppression of activity in the cerebral
      cortex and activation in the midbrain. These results indicate that both fetal and
      adolescent nicotine exposure elicit apparent damage to 5HT projections with
      reactive increases in regions containing 5HT cell bodies. Long-term changes in
      5HT innervation and/or synaptic activity may play a role in the subsequent
      development of depression in the offspring of women who smoke during pregnancy or
      in adolescent smokers.

PMID- 11578610
TI  - Vestibular modulation of plasma vasopressin levels in rats.
AB  - Recent studies, which have shown an increase of plasma vasopressin (VP) in
      experimental motion sickness and the efficacy of VP antagonists for motion
      sickness, suggest an important role of VP in the development of vestibulo
      autonomic responses. We have recently found evidence of the co-existence of
      vasopressinergic neurons with the stress-sensitive chemokinergic neuronal system
      in the hypothalamo-pituitary pathway in rats, which uses cytokine-induced
      neutrophil chemoattractant (CINC) as an effector molecule. In this study, to
      elucidate possible roles of VP and CINC in the vestibulo-autonomic responses, we
      simultaneously measured plasma VP and CINC concentrations after electrical or
      caloric vestibular stimulation in urethane-anesthetized rats. Electrical
      vestibular stimulation with more than 200 microA increased the plasma levels of
      VP in a current intensity-dependent manner, and stimulation with 500 microA
      increased the plasma VP levels to 350% of the normal control group, which
      received no stimulation. Caloric vestibular stimulation with cold water increased
      the plasma VP levels to 262% of the control group, which received caloric
      stimulation with water at 37 degrees C, and stimulation with warm water tended to
      increase the plasma VP levels. Plasma CINC levels were neither affected by
      electrical nor caloric vestibular stimulation. These findings indicate that
      vestibular stimulation increased plasma levels of VP but not CINC, and this
      vestibular-induced activation of VP neurons may be involved in a mechanism of
      vestibulo-autonomic responses.

PMID- 11578611
TI  - Minimal ischaemic neuronal damage and HSP70 expression in MF1 strain mice
      following bilateral common carotid artery occlusion.
AB  - Investigation into the influence of specific genes and gene products upon the
      pathophysiology of cerebral ischaemia has been greatly enhanced by the use of
      genetically modified mice. A simple model of global cerebral ischaemia in mouse
      is bilateral common carotid artery occlusion (BCCAo) and the neuropathological
      impact of BCCAo has been investigated in several mouse strains. Bilateral carotid
      occlusion produces extensive neuronal damage in C57Bl/6J strain mice and this
      damage is linked to posterior communicating artery (PcomA) hypoplasticity in the
      circle of Willis. In the present study, we investigated the effect of BCCAo in
      MF1 strain mice and compared them with C57Bl/6J mice. The neuropathological
      consequences of BCCAo were assessed using standard histochemical staining and
      heat shock protein 70 (HSP70) immunohistochemical staining (to demarcate cells
      that had been ischaemically stressed). The effect of BCCAo on mean arterial blood
      pressure (MABP) was also measured. The plasticity of the circle of Willis was
      recorded using carbon black perfusion. MF1 mice displayed significantly less
      ischaemic neuronal damage and HSP70 immunoreactivity compared to C57Bl/6J mice
      following 10-20 min BCCAo. Moreover, ischaemic neuronal damage and HSP70
      immunoreactivity in MF1 mice subjected to extended BCCAo (25-45 min) was never as
      extensive or widespread as that observed in C57Bl/6J mice after 20 min BCCAo.
      MABP in MF1 mice (102+/-5 mmHg) was significantly higher than in C57Bl/6J mice
      (87+/-5) during 20 min BCCAo. MABP in MF1 mice during 20 and 40 min (103+/-12
      mmHg) BCCAo remained above pre-occlusion values for the entire occlusion period.
      MF1 mice had significantly greater circle of Willis plasticity (more PcomAs) than
      C57Bl/6J mice did. These data indicate that MF1 mice are less susceptible to
      BCCAo than C57Bl/6J mice and that this could be due to maintained increases in
      MABP during BCCAo and the lower prevalence of abnormalities of the circle of
      Willis in MF1 mice.

PMID- 11578612
TI  - Inhibition of the glutamate transporter EAAC1 expressed in Xenopus oocytes by
      phorbol esters.
AB  - Recent evidence indicates that second messengers and protein kinases regulate the
      activity and expression of glutamate transporters. The aim of the present study
      was to determine if direct activation of protein kinases C or A modulates the
      activity of the sodium-dependent glutamate transporter EAAC1. EAAC1 modulation
      was studied in cRNA-injected Xenopus oocytes by measuring [3H]L-glutamate uptake
      or glutamate-evoked uptake currents. We found that activation of PKA was
      ineffective, whereas treatment with the PKC agonist phorbol 12-myristate 13
      acetate (PMA) caused a significant decrease in EAAC1 transport activity
      (IC(50)=44.7+/-12 nM). PMA-induced EAAC1 inhibition was PKC-mediated because the
      inhibition could be blocked by specific PKC inhibitors and incubation with the
      inactive 4alpha-phorbol-12,13-didecanoate (4alpha-PDD) did not affect EAAC1.
      Saturation studies of glutamate-evoked uptake currents showed that PMA-mediated
      inhibition was due to a decrease in I(max) with no change in K(m). PMA
      simultaneously decreased membrane capacitance (C(m)) and transport-associated
      current and increased cytosolic accumulation of EAAC1 protein, compared to
      control. These results suggest that PKC activation inhibits EAAC1 by promoting
      its retrieval from the plasma membrane. PMA also significantly decreased
      glutamate uptake in a Madin-Darby canine kidney (MDCK) cell line stably
      transfected with EAAC1 but enhanced EAAC1-mediated glutamate uptake in the rat C6
      glioma cells, consistent with previous observations. Because activation of PKC by
      phorbol esters leads to opposite effects on EAAC1 activity in different culture
      models, we conclude that the PKC-mediated regulation of EAAC1 is cell-type
      specific.

PMID- 11578613
TI  - Changes in reactive oxygen species (ROS) production in rat brain during global
      perinatal asphyxia: an ESR study.
AB  - A large body of evidence suggests that the production of reactive oxygen species
      (ROS) can play an important role in ischemic neuronal injury. However any studies
      has been performed in hypoxic conditions. In the present experiments we studied
      using electron spin resonance (ESR) techniques the ROS release in neostriatum of
      newborn rats subjected to acute perinatal asphyxia (PA) followed by various
      periods of reoxygenation. Pregnant rats' uteri still containing foetuses were
      taken out and subjected to PA by immersion in a 37 degrees C water bath during
      the following periods of time: 5, 10, 15, 19 and 20 min. After performing PA,
      animals were recovered and ROS measured after 0, 5, 15, 30 or 60 min of
      reoxygenation. Then, pups were sacrificed, their neostriatum removed and
      homogenised with N-tert.-butyl-alpha-phenylnitrone (PBN) and diethylenetriamine
      pentacetic acid (DPTA) in phosphate-buffered saline (PBS) and the formed
      complexes were extracted with ethyl acetate an analysed using an X-band ESR
      spectrometer. A significant release of ROS was detected at 19 and 20 min of PA
      after 5 min of reoxygenation. These data provide strong evidence that ROS could
      be involved in neuronal damage during PA.

PMID- 11578614
TI  - Aberrant induction of Par-4 is involved in apoptosis of hippocampal neurons in
      presenilin-1 M146V mutant knock-in mice.
AB  - Mutations in presenilin-1 (PS-1) have been shown to increase neuronal
      vulnerability to apoptosis in Alzheimer's disease (AD). Par-4 is a novel cell
      death-promoting protein associated with neuronal degeneration in AD. We
      previously reported that, in transfected PC12 cells, Par-4 seems to be involved
      in the neurodegenerative mechanisms of PS-1 mutations. However, direct evidence
      for a necessary role of Par-4 in the pathogenic mechanisms of PS-1 mutations in
      neurons is lacking. We recently generated and characterized presenilin-1 mutant
      M146V knock-in (PS-1 M146V KI) mice. We now report that expression of the mutant
      presenilin-1 in these mice induces early and exaggerated increase in Par-4
      expression in hippocampal neurons following glucose deprivation (an insult
      relevant to the pathogenesis of AD). Importantly, inhibition of Par-4 expression
      by antisense par-4 oligonucleotide treatment counteracts neuronal apoptosis
      promoted by M146V mutation of PS-1. Mitochondrial dysfunction and caspase-3
      activity induced by glucose deprivation was significantly exacerbated in
      hippocampal neurons expressing the mutant PS-1. Antisense par-4 treatment largely
      suppressed the adverse effect of the mutant PS-1 on mitochondrial dysfunction and
      caspase activation. These results provide evidence in hippocampal neurons that
      Par-4 is involved in the neurodegenerative cascades associated with PS-1 M146V
      mutation by acting relatively early in the apoptotic process before mitochondrial
      dysfunction and caspase-3 activation. Since levels of Par-4 are significantly
      increased in the hippocampus in human AD brain, the results of this study may
      provide a significant link between aberrant induction of Par-4 and the
      neurodegenerative cascades promoted by PS-1 mutations in AD.

PMID- 11578616
TI  - Acute stress-induced increases in thalamic CRH mRNA are blocked by repeated
      stress exposure.
AB  - Corticotropin-releasing hormone (CRH) coordinates multiple aspects of the stress
      response. Recently, CRH mRNA has been identified in two regions of the thalamus:
      the posterior nuclear group (Po), and a region located at the interface of the
      central medial and ventral posteromedial nucleus (parvicellular part) (CM-VPMpc).
      Previous studies demonstrated that in both regions CRH mRNA increases following 1
      h of restraint stress, suggesting involvement of thalamic CRH in processing
      somatosensory and visceral information related to stress. The current study was
      proposed to further understand the effects of repeated and acute restraint stress
      on levels of thalamic CRH mRNA. Adult male rats were assigned to one of four
      groups in a 2 (repeated stress, no repeated) x2 (acute, no acute) design. Brain
      sections were processed for CRH mRNA in situ hybridization. ANOVA revealed no
      main effects of acute or repeated stress in either thalamic region. However,
      significant interactions between acute and repeated stress for levels of CRH mRNA
      were found for both regions of the thalamus. Compared to the no stress condition,
      acute restraint significantly increased CRH mRNA in the Po (39%) and the CM-VPMpc
      (32%). Repeated restraint did not alter baseline CRH mRNA levels, but blocked the
      acute restraint-induced effects. Thus, while acute stress increases levels of
      thalamic CRH mRNA, repeated exposure to the same stressor is without effect and
      prevents the acute response. These findings add to data establishing a role for
      thalamic CRH in the stress response and suggest a mechanism that may underlie
      habituation to repeated stress exposure.

PMID- 11578615
TI  - Tetraethylammonium ions block the nicotinic cholinergic receptors of cochlear
      outer hair cells.
AB  - Cochlear outer hair cells (OHCs) express nicotinic acetylcholine receptors
      (nAChRs) whose calcium permeability allow the activation of co-localized Ca(2+)
      sensitive K+ channels (SK-type). The large organic cation tetraethylammonium
      (TEA) is known to block at millimolar concentration voltage-gated and Ca(2+)
      activated K+ currents in OHCs. In the present study, we show that extracellular
      TEA blocked much more efficiently, at micromolar concentrations, ACh-evoked K+
      currents in isolated guinea pig OHCs. The dose-inhibition curve indicated an
      IC(50) of 60 microM, a value two orders of magnitude lower than the one reported
      on SK or BK channels. The site of the blocking action was on the extracellular
      side of the plasma membrane since 10 mM intracellular TEA did not prevent or
      change the characteristics of the ACh-evoked K+ current. The block of this K+
      current in OHCs was mainly explained by a direct action of TEA at the nAChRs.
      Indeed, we demonstrated that extracellular TEA inhibited directly the ionotropic
      cation current flowing through the nAChRs (IC(50)=30 microM). This study
      demonstrated for the first time that extracellular TEA is an effective blocker of
      the OHCs' nAChRs.

PMID- 11578617
TI  - Histological changes in monoaminergic neurons of Long-Evans Cinnamon rats.
AB  - The Long-Evans Cinnamon rat, an animal model of Wilson's disease, is an inbred
      mutant strain with spontaneous hepatitis isolated from Long-Evans rats. The
      copper concentration in the brains of Long-Evans Cinnamon rats at 4 weeks of age
      was lower than that of controls, but higher than that of controls at 20 weeks of
      age. We investigated the tyrosine hydroxylase and 5-hydroxytryptamine
      immunoreactive fiber densities in the brains of Long-Evans Cinnamon rats aged 4,
      10, and 20 weeks by immunohistochemistry, comparing them with Long-Evans Agouti
      rats used as controls. Tyrosine hydroxylase immunoreactive fiber densities in the
      cingulate cortex, hippocampus and cerebellum in Long-Evans Cinnamon rats were
      significantly lower than those of Long-Evans Agouti rats at 4 and 10 weeks of
      age. On the other hand, 5-hydroxytryptamine immunoreactive fiber densities in the
      cingulate cortex, caudate-putamen, hypothalamus, and hippocampus in Long-Evans
      Cinnamon rats were significantly higher than those of controls at 4, 10 and 20
      weeks of age. In the cingulate cortex and caudate-putamen, 5-hydroxytryptamine
      immunoreactive fiber densities became gradually higher with age. The number of
      aberrant 5-hydroxytryptamine immunoreactive fibers in the cingulate cortex,
      caudate-putamen, hypothalamus and hippocampus in LEC rats was significantly
      higher than that of controls. The number of another type of aberrant 5
      hydroxytryptamine immunoreactive fibers, which were detected only at 20 weeks of
      age in the caudate-putamen in LEC rats was significantly higher than that of
      controls. These results suggest that age-dependent changes in copper
      concentrations of Long-Evans Cinnamon rats were related to changes in
      monoaminergic neuron systems.

PMID- 11578619
TI  - Autoradiographic mapping of 5-HT(1B) and 5-HT(1D) receptors in the post mortem
      human brain using [(3)H]GR 125743.
AB  - The distribution of 5-HT(1B) and 5-HT(1D) receptors in the human post mortem
      brain was examined using whole hemisphere autoradiography and the radioligand
      [(3)H]GR 125743. [(3)H]GR 125743 binding was highest in the substantia nigra and
      the globus pallidus. Lower levels were detected in the striatum, with the highest
      densities in the ventromedial parts. In the amygdala, the hippocampus, the septal
      region and the hypothalamus, lower [(3)H]GR 125743 binding was observed,
      reflecting low densities of 5-HT(1B/1D) receptors. In the cerebral cortex,
      binding was similar in most regions, although restricted parts of the medial
      occipital cortex were markedly more densely labeled. Binding densities were very
      low in the cerebellar cortex and in the thalamus. Two methods were used to
      distinguish between the two receptor subtypes, the first using ketanserin to
      block 5-HT(1D) receptors and the second using SB 224289 to inhibit 5-HT(1B)
      receptor binding. The autoradiograms indicated that in the human brain, the 5
      HT(1B) receptor is much more abundant than the 5-HT(1D) receptor, which seemed to
      occur only in low amounts mainly in the ventral pallidum. Although [(3)H]GR
      125743 is a suitable radioligand to examine the distribution of 5-HT(1B)
      receptors in the human brain in vitro, the selectivities of ketanserin and SB
      224289 are not sufficiently high to give definite evidence for the occurrence of
      the 5-HT(1D) receptor in the human brain.

PMID- 11578618
TI  - Female odors lead to rapid activation of mitogen-activated protein kinase (MAPK)
      in neurons of the vomeronasal system.
AB  - Pheromonal mediation of reproductive function proceeds along a neuroanatomical
      pathway that connects the vomeronasal organ (VNO) at the periphery with
      downstream target-sites in the amygdala and hypothalamus. The MAPK pathway is a
      prominent cascade linking receptor activation to induction of effectors such as c
      Fos. We addressed the question: Does a specific pheromone stimulus lead to
      activation (phosphorylation, P) of MAPK in the VN system of the male mouse?
      Phosphorylation of MAPK in the VN system was evaluated 15-30 min and 1.5-2 h
      after exposure to female odors, using immunocytochemical techniques. A rapid and
      transient cytoplasmic expression of PMAPK was noted in the VNO with a unique
      distribution of the expressing neurons in columns extending over the entire basal
      to apical axis. A rapid and sustained expression was noted in most amygdaloid and
      hypothalamic VN target-sites and also in a few amygdaloid and hypothalamic sites
      outside the traditional VN system. The extent of expression and the subcellular
      compartmentalization (nucleus, cytoplasm, processes) of PMAPK were region
      dependent. Of the VN target-sites, the accessory olfactory bulb (AOB) stood out
      in the lack of expression of PMAPK, in the high expression of the MAPK enzyme
      itself and in the massive of expression of c-Fos. This expression profile
      implicates another pathway(s) in mediating VNO signaling to the AOB. Our results
      are the first to demonstrate the use of PMAPK to trace functional pathways. Based
      on the wide cellular and intracellular expression of phosphorylated MAPK in the
      VN system, we propose that the MAPK pathway plays an important role in mediating
      female pheromone signaling in the male mouse.

PMID- 11578620
TI  - Glutamate receptor involvement in dentate granule cell epileptiform activity
      evoked by mossy fiber stimulation.
AB  - In many persons with temporal lobe epilepsy, dentate granule cells form an
      interconnected synaptic network. This recurrent mossy fiber circuit mediates
      reverberating excitation that may facilitate seizure propagation by synchronizing
      granule cell discharge. The involvement of specific glutamate receptors in
      granule cell epileptiform activity evoked by stimulating the mossy fibers was
      investigated with use of rat hippocampal slices superfused with bicuculline, with
      or without increasing [K+](o) to 6 mM. The occurrence of short-latency mossy
      fiber-evoked granule cell epileptiform activity in slices from pilocarpine
      treated rats correlated with the presence and extent of recurrent mossy fiber
      growth. Blockade of AMPA receptors nearly abolished the orthodromic component of
      the response; subsequent antagonism of kainate receptors as well appeared to have
      no further action. Antagonism of NMDA receptors reduced the duration of
      epileptiform discharge, but increased the amplitude of population spikes within
      the evoked burst. Thus AMPA and NMDA, but perhaps not kainate, receptors play an
      important role in this type of epileptiform activity. Activation of type II
      metabotropic glutamate receptors, which inhibits the release of glutamate from
      mossy fiber boutons, reduced the magnitude of epileptiform discharge. This action
      was reversed by a partial agonist of these receptors. However, neither an agonist
      nor an antagonist of type III metabotropic glutamate receptors significantly
      altered the response. Considering the importance of synchronous granule cell
      discharge for seizure propagation from the entorhinal cortex to the hippocampus,
      agonists of type II metabotropic glutamate receptors may be useful in suppressing
      such discharge both experimentally and clinically.

PMID- 11578621
TI  - Interaction of anandamide with the M(1) and M(4) muscarinic acetylcholine
      receptors.
AB  - The M(1) and M(4) muscarinic acetylcholine receptors are the most abundant
      muscarinic receptor subtypes in the brain, and are involved in learning and
      memory. Because cannabinoid receptors are also abundantly expressed in similar
      brain regions and mediate opposite effects to acetylcholine on cognition, the
      present study investigated whether the endocannabinoid agonist, anandamide, and
      its metabolically stable derivative, methanandamide, directly modified the
      binding properties of the human M(1) and M(4) receptors individually expressed in
      CHO cell membranes. Experiments utilized the antagonists, [(3)H]N
      methylscopolamine and [(3)H]quinuclidinyl benzilate. When acetylcholine was used
      as the inhibiting ligand, shallow, biphasic isotherms were observed at both
      receptors, characterised by similar apparent dissociation constants for high and
      low affinity binding at each receptor but with a greater proportion of high
      affinity sites at the M(4) (40-45%) than at the M(1) receptor (17-20%). In
      contrast, anandamide and methanandamide inhibited the binding of both
      radioligands over a narrow (low micromolar) concentration range, with monophasic
      isotherms characterized by Hill coefficients significantly greater than 1 at both
      receptors. These effects were not due to the vehicle used. Further saturation
      binding analyses found anandamide able to significantly reduce the apparent
      affinity and maximal density of binding sites labeled by [(3)H]quinuclidinyl
      benzilate. Interestingly, no significant inhibition of radioligand binding was
      noted using the synthetic cannabinoid agonist, WIN55212-2, or the cannabinoid
      CB(1) receptor antagonist, SR141716A. These data thus provide evidence for a
      direct role of anandamides in modulating muscarinic receptor binding properties
      through a non-competitive mechanism that is unrelated to their actions on
      cannabinoid receptors.

PMID- 11578623
TI  - Prenatal stress alters time characteristics and intensity of formalin-induced
      pain responses in juvenile rats.
AB  - Previous studies found that stressful events during pregnancy can alter the
      offspring's pain sensitivity to the phasic nociceptive stimuli. The present data
      constitute the first demonstration of the consequences of prenatal stress to
      formalin-induced pain in juvenile rats. Injection of formalin into a hind paw of
      a 25-day-old rat that had not been stressed prenatally produced the typical
      biphasic specific nociceptive behavioral response consisting of an early short
      phase lasting 1-4 min followed by a second prolonged phase (12-24 min). Between
      them there was an interphase that lasted 6-9 min during which the specific
      behaviors were not shown. This period is generally considered to be a period of
      inactivity. Prenatally stressed rat pups showed significant increase in
      flexing+shaking behaviors and in the duration of the second phase of formalin
      induced pain in flexing+shaking and licking behaviors and decrease of the
      duration of the interphase. Disinhibition of the pain behaviors during the
      interphase was greatly more pronounced in female than in male rats. Sex
      differences indicate increased vulnerability of inhibitory processes to prenatal
      stress in females compared with males. These data also underline the importance
      of understanding the nature of the interphase and provide data on the mechanisms
      that underlie that component of the formalin test.

PMID- 11578622
TI  - PKC and CaMKII dependent synaptic potentiation in cultured cerebral neurons.
AB  - We have reported that the long-lasting potentiation of spontaneous excitatory
      postsynaptic currents (SEPSCs) was induced by a Mg(2+)-free treatment in cultured
      chick cerebral neurons and a factor(s) extracellularly released during the
      treatment could induce the potentiation by itself. In this paper, protein kinase
      C (PKC) and calcium/calmodulin-dependent protein kinase type II (CaMKII) but not
      protein kinase A (PKA) were reported to contribute to the potentiation mechanism
      during a step between the activation of the N-methyl-D-aspartate receptors by the
      Mg(2+)-free treatment and the secretion of the protein factor(s).

PMID- 11578624
TI  - Synchronized population oscillation of excitatory synaptic potentials dependent
      of calcium-induced calcium release in rat neocortex layer II/III neurons.
AB  - We examined the roles played by calcium-induced calcium release from ryanodine
      sensitive calcium stores in induction of neocortical membrane potential
      oscillation by using caffeine, an agonist of ryanodine receptors. Intracellular
      recordings were made from neurons in layer II/III of rat visual cortex slices in
      a caffeine-containing medium. White matter stimulation initially evoked
      monophasic synaptic potentials. As low-frequency stimulation continued for over
      10 min, an oscillating synaptic potential gradually became evoked, in which a
      paroxysmal depolarization shift was followed by a 8-10-Hz train of several
      depolarizing wavelets. This oscillating potential was not induced in a medium
      containing no caffeine with 2 or 0.5 mM [Mg2+](o). Under blockade of N-methyl-D
      aspartate receptors, induction of this oscillating potential failed even with
      caffeine application. Experiments with the calcium store depletor, thapsigargin,
      revealed that this oscillating potential is induced in a manner dependent on
      intracellular calcium release. Dual intracellular recordings revealed that the
      oscillation was synchronized in pairs of layer II/III neurons. The oscillating
      potential was detectable by field potential recordings also, suggesting that the
      present oscillation seems to reflect a network property.

PMID- 11578625
TI  - Membrane current possessing the properties of a mechano-electric transducer
      current in inner hair cells of guinea-pig cochlea.
AB  - We measured the membrane current possessing the properties of a mechano-electric
      transducer current in isolated inner hair cells of guinea-pig cochlea. In a free
      standing hair bundle, depolarization to +80 mV evoked a stable outward current
      attributable to the opening of transducer channels, and repolarization to -80 mV
      evoked a transient inward current indicating adaptation. The time constant of
      adaptation increased as the membrane potential depolarized. Dihydrostreptomycin
      diminished both the outward and inward currents.

PMID- 11578626
TI  - Early decrease of redox factor-1 in spinal motor neurons of presymptomatic
      transgenic mice with a mutant SOD1 gene.
AB  - Oxidative stress has been proposed to play a pivotal role in pathogenesis of both
      sporadic and familial amyotrophic lateral sclerosis (ALS). Expression of DNA
      repair enzyme redox factor-1 (Ref-1) protein was examined in the spinal cord of
      transgenic mice with an ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) gene.
      Immunoblotting and immunocytochemical analyses showed that the most spinal motor
      neurons lost the immunoreactivity for Ref-1 in the early presymptomatic stage
      that preceded significant loss of the neurons. The present result suggests that
      an early impairment of DNA repair in the spinal motor neurons may account for the
      mutant SOD1-mediated motor neuronal death in this model.

PMID- 11578627
TI  - Effect of chronic stress on cholinergic transmission in rat hippocampus.
AB  - We previously demonstrated that chronic stress impaired prefrontal cortex
      sensitive working memory, but not reference memory. Since the hippocampal
      cholinergic system is also involved in these memories, we examined the effects of
      chronic stress on cholinergic transmission in the rat hippocampus. A
      microdialysis study revealed that the stress did not affect the basal
      acetylcholine release, but enhanced the KCl-evoked response. These results
      suggest that cholinergic transmission in the chronically stressed hippocampus
      does not contribute to working memory impairment, but it may be involved in
      maintenance of reference memory.

PMID- 11578628
TI  - Dietary iron reduces the anti-convulsion activity of phenytoin in
      electroconvulsion via inhibition of brain penetration.
AB  - We determined the anti-convulsion activity of phenytoin (PHT) using the maximum
      electron shock method in mice fed diets containing various concentrations of iron
      for 18 weeks. Dietary iron reduces the anti-convulsion activity of PHT in a dose
      dependent manner (0-6100 ppm). High concentrations of PHT are detected in the
      plasma of mice fed a high iron diet compared with those fed normal and low iron
      diets, in contrast to the pharmacological effect. However, the concentration of
      PHT in the brains of mice fed high amounts of dietary iron decreased
      significantly 3 h after treatment with PHT, consistent with the anti-convulsion
      effect of PHT. The relationship between brain and plasma-unbound concentrations
      of PHT indicates that the penetration of PHT into brain is significantly
      inhibited by dietary iron.

PMID- 11578629
TI  - Fluororuby as a marker for detection of acute axonal injury in rat spinal cord.
AB  - Axonal damage is a common pathological consequence of spinal cord injury.
      Previous studies have detected axonal injury with silver stains for degeneration
      or immunohistochemistry for alterations in components such as beta-amyloid
      precursor protein, neurofilament or ubiquitin. Fluororuby has recently been
      introduced as a neuronal tracer in studies of spinal cord injury and
      regeneration. Our study was carried out to determine whether Fluororuby can be
      used to identify injured axons and monitor the time course of axonal damage.
      Adult rats underwent needle puncture injury to the white matter in the midline
      and lateral spinal cord at T11. At the same time, 0.05 microl of Fluororuby was
      injected into the cord at the same sites. After survival times ranging from 6 h
      to 3 weeks, spinal cords were cut into longitudinal frozen sections and examined
      with confocal microscopy. Fluororuby was found to label key features of axonal
      injury including axonal swelling, retraction balls and disrupted axons. Damaged
      axons close to the injury site were consistently labeled within 6 h, with
      indications of swollen and disconnected axons spreading further from the site
      during the first week. Fewer injured axons were labeled after 1 week survival,
      but the marker revealed longer distances of degenerating axons both distal and
      rostral to the injury site. Our findings indicate that Fluororuby is a quick,
      sensitive, reliable and technically simple fluorescent marker for early stages of
      acute axonal injury and degeneration.

PMID- 11578630
TI  - Synthesis of hydantocidin and C-2-thioxo-hydantocidin.
AB  - Hydantocidin, a naturally occurring strong herbicide, was synthesized in an
      overall yield of 35.2%, with the accompanying 1'-epi-hydantocidin in overall 9.6%
      yield from 2,3-O-isopropylidene-D-ribono-1,4-lactone. C-2-thioxo-hydantocidin and
      its spiro-epimer were also synthesized in an overall yield of 14.4% and 8.5%,
      respectively.

PMID- 11578631
TI  - Interaction of metal ions with N-glycosylamines: isolation and characterization
      of the products of 4,6-O-benzylidene-N-(o-carboxyphenyl)-beta-D
      glucopyranosylamine with different metal ions.
AB  - Metal-ion complexes of Li(+), Na(+), K(+), Mg(2+), Ca(2+), Ba(2+), Pb(2+),
      Cd(2+), Hg(2+) with 4,6-O-benzylidene-N-(o-carboxyphenyl)-beta-D
      glucopyranosylamine were synthesized and isolated as solid products and
      characterized by analytical means as well as by spectral techniques, such as, 1H
      and 13C NMR, FTIR, absorption, FAB mass spectrometry, optical rotation and CD.
      While the alkali metal ions formed ML type of complexes, the other metal ions
      formed ML(2) type complexes. Molecular weights of the complexes of Li(+), Na(+)
      and K(+) were established based on the molecular-ion peaks in the FAB mass
      spectra. The saccharide portion remains in the beta-anomeric form even after the
      complexation. The spectral data, as well as the trends observed in the chemical
      shifts, indicate the interaction preferences between this glycosyl amine and
      different metal ions, and further reveal certain structural features of the
      complexes.

PMID- 11578632
TI  - Thiosugar nucleotide analogues: synthesis of uridine 5'-(2,3,6-tri-O-acetyl-4-S
      acetyl-4-thio-alpha-D-galactopyranosyl diphosphate).
AB  - The synthesis of a novel uridine diphosphate galactose (UDP-Gal) analog, (UDP
      2,3,6-tri-O-acetyl-4-S-acetyl-4-thio-alpha-D-galactopyranose) (10) is described.
      Compound 10 contains a sulfur in the place of oxygen at the 4-position of the
      galactose moiety. Compound 10 represents a protected form of a novel sugar
      nucleotide analog that can potentially be used during chemoenzymatic synthesis to
      modify complex oligosaccharides.

PMID- 11578633
TI  - Synthesis of a set of di- and tri-sulfated galabioses.
AB  - Among cell-adhesion molecules, L-selectin recognizes sulfated sLe(x) with
      relatively low affinity. Here, we aimed at artificial mimics by synthesizing a
      set of di- and tri-sulfated galabioses, which may surpass the affinity of
      sulfated sLe(x). As a strategy to obtain 3',6',6-tri-O-sulfogalabioses,
      regioselective reductive cleavage of 4,6- and 4',6'-di-O-benzylidenegalabioses
      was employed. Two suitably protected galactose precursors were conjugated to
      yield alpha and beta anomers (48 and 18%, respectively) by using a pentenyl
      galactoside donor and iodinium di-sym-collidine perchlorate as the catalyst. For
      synthesizing the 3',6-di-O-sulfogalabiose, however, a trichloroacetimidate donor
      was superior (52%) to the pentenyl one (30%).

PMID- 11578634
TI  - Three-dimensional structure of the sodium salt of iota-carrageenan.
AB  - The three-dimensional structure of the sodium salt of iota-carrageenan has been
      determined by using X-ray diffraction data collected from its polycrystalline and
      oriented fibers. The molecule forms a half-staggered, parallel, threefold, right
      handed double helix that is stabilized by interchain hydrogen bonds from 2- and 6
      hydroxyl groups in the galactosyl units. Three helices are organized in a
      trigonal unit cell, of dimensions a=24.02 and c=12.93 A, with a lateral
      separation of 13.9 A for each pair. Both 2- and 4-sulfate groups are essential in
      helix-helix interactions that are mediated only by sodium ions and water
      molecules.

PMID- 11578635
TI  - A convenient preparation of aldonohydroxamic acids in water and crystal structure
      of L-erythronohydroxamic acid.
AB  - Hydroxamic acids derived from aldonic acids, namely aldonohydroxamic acids, have
      become an increasingly important class of inhibitors of enzymes involved in the
      metabolism of carbohydrates. We now report the straightforward preparation of
      various types of aldonohydroxamic acids by a new methodology involving the use of
      commercial 50% aqueous hydroxylamine as the source of the free base hydroxylamine
      that reacts directly with the corresponding aldonolactone dissolved in water. The
      reaction proceeds almost instantaneously in water at room temperature, yielding
      generally pure products in quantitative yield. To date, this methodology is
      probably the most facile and efficient way to synthesize aldonohydroxamic acids.
      We also determined by X-ray diffraction analysis the first crystal structure of a
      free aldonohydroxamic acid reported to date. Crystals of L-erythronohydroxamic
      acid belonged to the monoclinic system, space group P2(1), a=5.511(3),
      b=7.556(1), c=8.071(3) A, beta=109.10 degrees, and Z=2.

PMID- 11578636
TI  - Acetyl substitution of the O-specific polysaccharide caryophyllan from the phenol
      phase of Pseudomonas (Burkholderia) caryophylli.
AB  - The intact O-specific caryophyllan polysaccharide of the lipopolysaccharide
      fraction from the bacterium Pseudomonas (Burkholderia) caryophylli was isolated
      for the first time. Its structure was clarified by means of chemical and
      spectroscopic analysis and consisted of a homopolymer of randomly acetylated
      caryophyllose units. The position of acetyl groups when present is not unique:
      all the hydroxyl-groups on the side chain of the sugar can be substituted with a
      slight preference for acetylation of the C-5-C-10 tail of this unusual
      monosaccharide

PMID- 11578637
TI  - The dimeric complex of cyclomaltoheptaose with 1,14-tetradecanedioic acid.
      Comparison with related complexes.
AB  - The structure of the complex of cyclomaltoheptaose (beta-cyclodextrin, betaCD)
      with 1,14-tetradecanedioic acid has been determined and refined to a final
      R=0.0693 based on 9824 observed reflections. Each diacid molecule threads through
      two betaCD monomers arranged in dimers thus, forming a [3]pseudorotaxane. The end
      carboxylic groups of adjacent dimers, far apart and fully hydrated, are
      associated indirectly through water molecules. The positioning of the carboxylic
      groups with respect to the betaCD dimer and the H-bonds with water molecules are
      very similar to these of the corresponding complexes of the diacids with 12 and
      13 carbon atoms. The bending in the middle of the aliphatic chain is more
      prominent, compared to that of the corresponding guests with less carbon atoms,
      thus the end carboxylic groups stay in the same height of the primary faces of
      the betaCD dimeric complex. As a consequence of the present structure, more close
      contacts are observed between calculated H-atoms of the guest and O-atoms of the
      host inside the cavity. This bending is allowed by the width of the betaCD dimer
      cavity at the secondary interface region.

PMID- 11578638
TI  - Transcranial magnetic stimulation as a therapeutic tool in psychiatry: what do we
      know about the neurobiological mechanisms?
AB  - Potential therapeutic properties of repetitive transcranial magnetic stimulation
      (rTMS) have been suggested in several psychiatric disorders such as depression,
      mania, obsessive-compulsive disorder, posttraumatic stress disorder and
      schizophrenia. By inducing electric currents in brain tissue via a time-varying
      strong magnetic field, rTMS has the potential to either directly or trans
      synaptically modulate neuronal circuits thought to be dysfunctional in these
      psychiatric disorders. However, in order to optimize rTMS for therapeutic use, it
      is necessary to understand the neurobiological mechanisms involved, particularly
      the nature of the changes induced and the brain regions affected. Compared to the
      growing number of clinical studies on its putative therapeutic properties, the
      studies on the basic mechanisms of rTMS are surprisingly scarce. rTMS currently
      still awaits clinical routine administration although,there is compelling
      evidence that it causes changes in neuronal circuits as reflected by behavioural
      changes and decreases in the activity of the hypothalamic-pituitary
      adrenocortical system. Both alterations suggest regional changes in
      neurotransmitter/neuromodulator release, transsynaptic efficiency, signaling
      pathways and in gene transcription. Together, these changes are, in part,
      reminiscent of those accompanying antidepressant drugs.

PMID- 11578639
TI  - Influence of 5-HTTLPR and TPH variants on illness time course in mood disorders.
AB  - The aim of our study was to investigate gene variants in the long-term outcome of
      mood disorders. We retrospectively studied a sample of inpatients affected by
      recurrent and rapid cycling mood disorders. The serotonin transporter gene-linked
      functional polymorphic region (5-HTTLPR) and the A218C tryptophan hydroxylase
      (TPH) gene variant were determined using a PCR-based technique. For 5-HTTLPR
      polymorphism we genotyped 435 inpatients affected by major depressive (n=153),
      bipolar (n=213) and rapid cycling (n=69) mood disorders and 456 controls; for TPH
      we genotyped 399 inpatients (MD, n=132; BP, n=203; rapid cycling n=64) and 259
      controls. Random Regression Model analysis was used to investigate the
      longitudinal time course of the illness. 5-HTTLPR and TPH polymorphisms were not
      associated with mood disorders time course. However we observed an excess of 5
      HTTLPR*long alleles among rapid cycling subjects compared to both controls
      (P=0.018) and remitting mood disorders (P=0.006). TPH frequencies did not differ
      between mood disorders subtypes. Our results suggest that 5-HTTLPR variants may
      confer a susceptibility toward rapid cycling mood disorders.

PMID- 11578640
TI  - Enlarged cerebellar vermis in Williams syndrome.
AB  - Williams syndrome (WMS) is a rare genetic disorder characterized by relative
      preservations of language ability and facial processing despite deficits in
      overall intelligence, problem solving, and visuospatial processing. Subjects with
      WMS also display hypersocial behavior and excessive linguistic affect during
      conversations and when giving narratives. Neuroimaging studies have shown global
      reductions in the brain volumes of subjects with WMS compared with normal
      controls, but with preservations in cerebellar volume. This study examines the
      neuroanatomic structure of the cerebellar vermis in 20 subjects with WMS and 20
      age- and gender-matched controls via high-resolution magnetic resonance imaging.
      The vermis was divided into lobules I-V, VI-VII, and VIII-X. Lobules VI-VII and
      VIII-X were both relatively enlarged in the WMS group, and after adjusting for
      the smaller size of the WMS brain, the posterior vermis was significantly larger
      in WMS (Mann-Whitney z-value=4.27; P<0.001). Given that reductions in posterior
      vermis size have been implicated in flattened affect and autistic features,
      increased vermis size in subjects with WMS may be related to the hypersociality
      and heightened affective expression characteristic of individuals with this
      genetic condition.

PMID- 11578641
TI  - Gender-specific alterations of cerebral metabolites with aging and cortisol
      treatment.
AB  - Excess availability of the adrenocortical glucocorticoid hormone cortisol has
      been correlated with structural brain changes and a decline of cognitive
      functions during aging. Pertinent studies need to consider gender as a potential
      confound because of sexual dimorphism in the regulation of hypothalamus-pituitary
      adrenal axis activity. In vivo localized proton magnetic resonance spectroscopy
      of male and female tree shrews revealed similar concentrations of cerebral
      metabolites in young adult animals but gender-specific alterations with aging as
      well as in response to cortisol treatment. In comparison with adult tree shrews,
      aged males had reduced concentrations of N-acetylaspartate (-33%; P<0.01) and
      total creatine (-34%; P< 0.01). These findings are in line with the occurrence of
      neuronal loss. In contrast, aged females exhibited increased concentrations of
      choline-containing compounds (+27%; P<0.05) which--together with a tendency for
      increased creatine (+24%) and myo-inositol (+14%)--is indicative of glial
      proliferation. After chronic administration of cortisol (4 mg/day for 28 days),
      male but not female tree shrews showed a specific reduction of the choline
      containing compounds (-29%; P< 0.05). The observed sex differences with age are
      likely to result from differences in the regulation of stress-related hormones
      which is further supported by the gender-specific responses to cortisol.

PMID- 11578643
TI  - Obstetric complications and Apgar score in early-onset schizophrenic patients
      with prominent positive and prominent negative symptoms.
AB  - The objective of the study was to find associations between obstetric
      complications (OCs) history and schizophrenia course and symptoms. We analysed
      the obstetric and psychiatric history of 50 DSM IV schizophrenic subjects who
      experienced their first schizophrenia episode in adolescence, and 30 healthy
      controls. Obstetrical data and Apgar scores were obtained from medical records
      and evaluated with the Lewis and Murray Scale. Based on patients' documentation
      [including longitudinal evaluation with Positive and Negative Syndrome Scale
      (PANSS)] the symptom profile and the course of schizophrenia were determined.
      RESULTS: we distinguished two major groups of patients: with prominent negative
      and prominent positive symptoms. Schizophrenics with prominent negative symptoms
      and a chronic schizophrenia course had significantly more definite OCs and lower
      Apgar scores than patients with prominent positive symptoms and controls.
      Subjects who had a positive OCs history were more than four times likely to
      develop schizophrenia in adolescence than those without such a history (OR=4.64;
      95% CI=1.29-17.51) with the likelihood of developing schizophrenia with prominent
      negative symptoms especially high (OR=7.31; 95% CI=1.80-29.65). An Apgar score of
      between 0 and 3 after birth was associated with an increased risk for developing
      schizophrenia (OR=2.25; 95% CI=0.56-9.12), especially with prominent negative
      symptoms (OR=3.71; 95% CI=0.84-16.32). The findings support the hypothesis of a
      role of OCs in developing early-onset schizophrenia and suggest the associations
      of the OCs history with a specific symptoms profile (prominent negative symptoms)
      and a chronic course of schizophrenia.

PMID- 11578642
TI  - Sleep deprivation and hypothalamic-pituitary-adrenal (HPA) axis activity in
      depressed patients.
AB  - In the present study we investigated HPA axis activity in depressed patients
      treated with partial sleep deprivation (PSD) in order to identify
      endocrinological characteristics related to PSD responsiveness. Thirty-three drug
      free patients (14 men, 19 women) suffering from major depression according to DSM
      IV criteria were treated with PSD. Response to PSD was defined as a reduction of
      at least 30% according to the 6-item version of the Hamilton Depression Scale (6
      HAMD). Subsequently, the combined dexamethasone-suppression/CRH-stimulation test
      (DEX/CRH test) was performed. Patients were pretreated with 1.5 mg dexamethasone
      (DEX) at 23:00 h and challenged with 100 microg corticotropin-releasing hormone
      (CRH) the following day. Postdexamethasone cortisol concentrations (before CRH
      administration) served as parameters for the DST status (dexamethasone
      suppression test). The cortisol stimulation after CRH was used as measurement for
      the DEX/CRH test status. Of the depressive patients, 54.5% (18 out of 33)
      responded to PSD. DST suppressors (postdexamethasone cortisol levels < 15 ng/ml)
      showed a significantly greater reduction in 6-HAMD scores after PSD than DST
      nonsuppressors. Furthermore, a significant negative correlation between
      postdexamethasone cortisol levels and reduction in 6-HAMD scores after PSD could
      be established. However, there was no relationship between the cortisol
      stimulation following CRH challenge and response to PSD. Although the combined
      DEX/CRH challenge test is a more sensitive marker for HPA axis dysregulation in
      depression than the standard DST, the negative feedback of the HPA system
      reflected by the DST status is apparently more closely associated with response
      to partial sleep deprivation in major depressive disorder.

PMID- 11578645
TI  - LASIK complications: etiology, management, and prevention.
AB  - Laser in situ keratomileusis (LASIK) is a rapidly evolving ophthalmic surgical
      procedure. Several anatomic and refractive complications have been identified.
      Anatomic complications include corneal flap abnormalities, epithelial ingrowth,
      and corneal ectasia. Refractive complications include unexpected refractive
      outcomes, irregular astigmatism, decentration, visual aberrations, and loss of
      vision. Infectious keratitis, dry eyes, and diffuse lamellar keratitis may also
      occur following LASIK. By examining the etiology, management, and prevention of
      these complications, the refractive surgeon may be able to improve visual
      outcomes and prevent vision-threatening problems. Reporting outcomes and mishaps
      of LASIK surgery will help refine our approach to the management of emerging
      complications.

PMID- 11578646
TI  - von Hippel-Lindau disease.
AB  - In recent years advances have been made in the clinical and genetic aspects of
      von Hippel-Lindau disease (VHL). Retinal capillary hemangioma is the most common
      manifestation of VHL disease and, therefore, ophthalmologists are frequently
      involved in the care of patients with this disease. The incidence of VHL disease
      is approximately 1 in 40,000 live births. It is estimated that there are
      approximately 7000 patients with VHL disease in the USA. The inheritance of VHL
      disease is autosomal dominant with high penetrance. Depending on the clinical
      circumstances, retinal capillary hemangioma may be managed by observation, laser
      photocoagulation, cryotherapy, and plaque radiotherapy. Typical extraocular
      lesions associated with VHL disease are central nervous system hemangioma, renal
      cyst, renal carcinoma, pancreatic cysts and adenoma, pancreatic islet cell
      tumors, pheochromocytoma, endolymphatic sac tumor of the inner ear, and
      cystadenoma of the epididymis and the broad ligament. The life expectancy of
      affected individuals may be improved by early detection and treatment of varied
      manifestations with the use of surveillance protocols. Identification of the VHL
      gene on chromosome 3p25-26 has now made it possible for suspected individuals to
      undergo genetic testing with a high degree of accuracy. We review herein the
      ophthalmic manifestations and treatment of retinal capillary hemangioma and
      systemic findings of the VHL disease.

PMID- 11578647
TI  - Sudden painless visual loss.
AB  - Common signs and symptoms of temporal arteritis include headache, scalp
      tenderness, jaw claudication, anemia, and an elevated sedimentation rate (ESR).
      Severe complications can include blindness, retinal artery occlusion, and optic
      neuropathy. While temporal arteritis may be suggested by patient history, other
      causes that can mimic its presentation must be considered, especially when visual
      loss occurs in the setting of a normal funduscopic exam. We report a case of
      invasive sino-orbital aspergillosis that mimicked the clinical signs and symptoms
      typically associated with temporal arteritis. A high index of suspicion and
      appropriate radiological and laboratory studies prevented delays in formulating
      the correct diagnosis and treatment plan.

PMID- 11578648
TI  - Autosomal dominant Stargardt-like macular dystrophy.
AB  - Autosomal dominant Stargardt-like macular dystrophy is one of the early onset
      macular dystrophies. It is characterized clinically in its early stages by visual
      loss and by the presence of atrophic macular changes with or without the presence
      of yellowish flecks. It is an important retinal dystrophy to study, not only
      because it has implications in the care and treatment of patients with the
      condition, but because it also provides important information regarding retinal
      function. Review of the literature suggests that many of the reported families
      are linked to chromosome 6q. Genetic and genealogical evidence suggests that
      these families have descended from a common ancestor or founder. The recent
      identification of a disease-causing gene that is involved in fatty acid
      metabolism may have implications in the study of the more common age-related
      macular degeneration. We review the recent clinical, genetic, and genealogical
      aspects of autosomal dominant Stargardt-like macular dystrophy.

PMID- 11578649
TI  - Juvenile xanthogranuloma masquerading as pediatric chronic uveitis: a
      clinicopathologic study.
AB  - Juvenile xanthogranuloma (JXG) is a rare, pediatric histiocytic skin disorder
      that may affect the eye. It can present with protean ocular manifestations,
      including masquerade uveitis, heterochromia, hyphema, or glaucoma. It very rarely
      involves the retina and posterior segment; indeed, posterior involvement has been
      documented histopathologically in only one case. We present the case of a 2-year
      old child with ocular JXG presenting as chronic, refractive uveitis, without skin
      or systemic findings. The blind, painful eye was enucleated and found to harbor a
      diffuse histiocytic process that involved both the anterior and posterior
      segments, including the retina and subretinal space. Histological,
      immunohistochemical, and electron microscopic studies confirmed the diagnosis of
      JXG. The pathologic classification and differential diagnosis of systemic
      histiocytic disorders are discussed. Since JXG can present as masquerade
      pediatric uveitis, this entity should be considered in children with atypical
      uveitis. In rare instances, JXG may involve the posterior segment and the retina,
      leading to retinal detachment and blindness.

PMID- 11578650
TI  - Anesthesia for intraocular surgery.
AB  - Surgeons must decide on the type of anesthesia to use when performing cataract
      surgery. These "viewpoints" articles provide a well-balanced discussion offering
      the pros and cons of both topical anesthesia and retrobulbar/peribulbar
      injection. Dr. Dutton gives an overview of both techniques, focusing on relevant
      orbital anatomy. Drs. Hassan, Edelhauser and Kim, review the various types of
      topical anesthesia currently in use, and Drs. Spriggs and Broocker examine
      retrobulbar and peribulbar injections. Both techniques are associated with
      advantages and risks, so each surgeon must decide which technique is best suited
      for his or her own practice.

PMID- 11578653
TI  - Doctor Rush's eye water and the opening of the American west.
AB  - It has now been almost 200 years since Meriwether Lewis and William Clark set out
      from St. Louis on their successful western exploration in search of a practical
      overland and water route to the Pacific Ocean. Prior to their departure, Lewis
      traveled to Philadelphia to seek advice from the famous Dr. Benjamin Rush and
      others. Rush provided him with an elementary medical education, a liberal supply
      of his famous purgative pills, a chest of medical instruments, and a recipe for a
      lead acetate eye wash, together with the chemicals needed for its manufacture. In
      their journals, Lewis and Clark make frequent allusions to various eye
      afflictions suffered by their own troops and by the Native Americans encountered
      on their journey. Although herbal remedies were in common use, Rush's eye water
      proved very popular among the Native Americans for relief of their pain. It was
      so popular, in fact, that the explorers were able to make good use of it as
      diplomatic currency.

PMID- 11578654
TI  - When it's okay to say you're sorry.
AB  - Traditionally, physicians have been warned not to express sympathy to a patient
      whose treatment has not been successful, lest such a statement could be construed
      as an admission of liability in a court of law. It is now realized that a patient
      whose physician expresses sympathy is less likely to bring suit than a patient
      who feels angry and alone in his or her disappointment. Fortunately, legislation
      is being passed in some states which disallows the admissibility of a physician's
      "benevolent gesture" in court.

PMID- 11578656
TI  - Dietary agents in cancer prevention: flavonoids and isoflavonoids.
AB  - Flavones and isoflavones may play a prominent role in cancer prevention since
      these compounds are found in numerous plants that are associated with reduced
      cancer rates. This article reviews recent epidemiological and animal data on
      isoflavones and flavones and their role in cancer prevention. It covers aspects
      of the bioavailability of these dietary constituents and explores their mechanism
      of action. Human epidemiology data comes primarily from studies in which foods
      rich in isoflavones or flavones are associated with cancer rates. This approach
      has been particularly useful with isoflavones because of their abundance in
      specific foods, including soy foods. The bioavailability of flavones and
      isoflavones has been shown to be influenced by their chemical form in foods
      (generally glycoside conjugates), their hydrophobicity, susceptibility to
      degradation, the microbial flora of the consumer, and the food matrix. Some
      information is available on how these factors influence isoflavone
      bioavailability, but the information on flavones is more limited. Many mechanisms
      of action have been identified for isoflavone/flavone prevention of cancer,
      including estrogenic/antiestrogenic activity, antiproliferation, induction of
      cell-cycle arrest and apoptosis, prevention of oxidation, induction of
      detoxification enzymes, regulation of the host immune system, and changes in
      cellular signaling. It is expected that some combination of these mechanisms will
      be found to be responsible for cancer prevention by these compounds. Compelling
      data suggest that flavones and isoflavones contribute to cancer prevention;
      however, further investigations will be required to clarify the nature of the
      impact and interactions between these bioactive constituents and other dietary
      components.

PMID- 11578655
TI  - Differentiation therapy of human cancer: basic science and clinical applications.
AB  - Current cancer therapies are highly toxic and often nonspecific. A potentially
      less toxic approach to treating this prevalent disease employs agents that modify
      cancer cell differentiation, termed 'differentiation therapy.' This approach is
      based on the tacit assumption that many neoplastic cell types exhibit reversible
      defects in differentiation, which upon appropriate treatment, results in tumor
      reprogramming and a concomitant loss in proliferative capacity and induction of
      terminal differentiation or apoptosis (programmed cell death). Laboratory studies
      that focus on elucidating mechanisms of action are demonstrating the
      effectiveness of 'differentiation therapy,' which is now beginning to show
      translational promise in the clinical setting.

PMID- 11578657
TI  - Autonomic control of the venous system in health and disease: effects of drugs.
AB  - The venous system contains approximately 70% of the blood volume. The sympathetic
      nervous system is by far the most important vasopressor system in the control of
      venous capacitance. The baroreflex system responds to acute hypotension by
      concurrently increasing sympathetic tone to resistance, as well as capacitance
      vessels, to increase blood pressure and venous return, respectively. Studies in
      experimental animals have shown that interference of sympathetic activity by an
      alpha1- or alpha2-adrenoceptor antagonist or a ganglionic blocker reduces mean
      circulatory filling pressure and venous resistance and increases unstressed
      volume. An alpha1- or alpha2-adrenoceptor agonist, on the other hand, increases
      mean circulatory filling pressure and venous resistance and reduces unstressed
      volume. In humans, drugs that interfere with sympathetic tone can cause the
      pooling of blood in limb as well as splanchnic veins; the reduction of cardiac
      output; and orthostatic intolerance. Other perturbations that can cause postural
      hypotension include autonomic failure, as in dysautonomia, diabetes mellitus, and
      vasovagal syncope; increased venous compliance, as in hemodialysis; and reduced
      blood volume, as with space flight and prolonged bed rest. Several alpha
      adrenoceptor agonists are used to increase venous return in orthostatic
      intolerance; however, there is insufficient data to show that these drugs are
      more efficacious than placebo. Clearly, more basic science and clinical studies
      are needed to increase our knowledge and understanding of the venous system.

PMID- 11578658
TI  - Dopamine D3 receptor as a therapeutic target for antipsychotic and
      antiparkinsonian drugs.
AB  - The cloning of the gene for the D3 receptor and subsequent identification of its
      distribution in brain and pharmacology allowed for serious consideration of the
      possibility that it might be a target for drugs used to treat schizophrenia and
      Parkinson's disease (PD). That is because it is highly expressed in limbic
      regions of the brain, exhibits low expression in motor divisions, and has
      pharmacologic similarity to the D2 receptor. Thus, antipsychotics that were
      presumed to block D2 receptors also had high affinity for the D3 receptor.
      Dopamine agonists used to treat the clinical symptoms of PD also have high
      affinity for the D3 receptor, and two D3 receptor-preferring agonists were found
      to be effective for treatment of PD. Many compounds achieving high potency and
      selectivity are now available, but few have reached clinical testing. Recent
      findings with respect to the anatomy of this receptor in human brain, altered
      expression in schizophrenia and PD, and biological models to study its function
      support the proposal that it is a target for development of drugs to alleviate
      symptoms in neuropsychiatric and neurologic disorders. Because of distinct
      aspects of regulation of the D3 receptor, it represents a unique target for
      therapeutic intervention in schizophrenia without high potential for unintended
      side effects such as tardive dyskinesia. It may also be that D3 receptor agonists
      can provide neuroprotective effects in PD and can modify clinical symptoms that
      D2 receptor-preferring agonists cannot provide.

PMID- 11578659
TI  - Artemisinin and its derivatives: an important new class of antimalarial agents.
AB  - Artemisinin and its derivatives are a potent new class of antimalarials,
      originated from Artemisia annua, L. The clinical efficacy of these drugs is
      characterized by an almost immediate onset and rapid reduction of parasitaemia.
      Their efficacy is high in such areas as well where multidrug-resistance is
      rampant, but in these areas, their combination with other (effective)
      antimalarials (e.g., mefloquine) is highly recommended. In this short review, the
      chemical structures, pharmacological properties, and clinical uses of artemisinin
      drugs are discussed.

PMID- 11578660
TI  - Cell imaging and morphology: application to studies of inherited purine metabolic
      disorders.
AB  - A number of inherited or drug-induced metabolic disorders involving dysfunctions
      in purines and pyrimidines are strongly associated with neurological dysfunction,
      e.g., Lesch Nyhan syndrome. Such disorders have been studied extensively using
      biochemical and molecular techniques in order to examine how such defects occur,
      sometimes using in vitro models based upon cultured neuroblastoma cell lines.
      However, these metabolic dysfunctions may manifest their effects in other ways,
      such as impaired synaptic transmission and gross abnormalities in neuronal growth
      and differentiation. This review outlines the latter novel facet of purine
      research. It is proposed that by employing cell imaging techniques and cultured
      neuroblastoma cell lines, believed to model the nervous system, significant
      insights into how inherited disorders of purine metabolism affect neuronal
      development can be obtained. This review provides an example of the application
      of these techniques to understand the etiology of Lesch Nyhan syndrome, and
      encourages further study of the role of purines and pyrimidines in the
      development of the nervous system.

PMID- 11578662
TI  - Functional cerebral asymmetry in affective disorders: new facts contributed by
      transcranial magnetic stimulation.
AB  - A growing body of experimental data usually finds a slightly lower activation in
      the left hemisphere than in the right in depressive syndromes, whereas the
      opposite occurs in mania. Transcranial magnetic stimulation (TMS) seems to have a
      distinctive lateralized effect with manic or depressed patients. These clinical
      findings provide new elements for discussion of the significance of unbalanced
      hemispherical activation as a biological substrate in affective disorders. Based
      on these data and on the theories of chaos and complexity, a hypothesis for the
      physiopathology of affective disorders and the functional mechanism of TMS is
      proposed. This hypothesis is in agreement with valence theory.

PMID- 11578661
TI  - Cyclic ADP-ribose as a second messenger revisited from a new aspect of signal
      transduction from receptors to ADP-ribosyl cyclase.
AB  - Cyclic ADP-ribose (cADPR), an endogenous modulator of ryanodine receptor Ca(2+)
      releasing channels, is found in various tissues. Cytosolic injection of cADPR
      induces an elevation of intracellular Ca(2+) concentrations or potentiates Ca(2+)
      increases. cADPR facilitates neurotransmitter or insulin release and modifies
      ionic currents. cADPR is synthesized by ADP-ribosyl cyclase and is metabolized by
      cADPR hydrolase. ADP-ribosyl cyclase activity is up-regulated by nitric
      oxide/cyclic GMP-dependent phosphorylation or receptor stimulation via G-proteins
      within membranes. These findings suggest that cADPR is a second messenger in
      cellular Ca(2+) signaling. However, many intriguing issues remain to be addressed
      before this identity is confirmed.

PMID- 11578663
TI  - Differential frontal activation in schizophrenia and bipolar illness during
      verbal fluency.
AB  - INTRODUCTION: The precise nature of frontal lobe dysfunction in schizophrenia
      remains unclear. We have previously demonstrated, using fMRI, a task-specific
      attenuation of frontal activation in schizophrenic patients. By using an
      identical methodology in matched bipolar subjects, we sought to determine whether
      this finding is specific to schizophrenia or a correlate of psychosis in general.
      METHOD: Five dextral male bipolar patients and matching groups of schizophrenic
      subjects and controls were studied using fMRI. Echoplanar images were acquired
      while subjects performed two paced tasks: covert verbal fluency and a semantic
      decision task. Generic brain activation maps were constructed from individual
      images by sinusoidal regression analysis. Between-group differences in the mean
      power of experimental response were identified on a voxel-wise basis by an
      analysis of variance (ANOVA). RESULTS: The bipolar patients showed extensive
      prefrontal activation during verbal fluency which was significantly greater than
      in controls. There was no difference in the prefrontal BOLD response during the
      semantic decision task. CONCLUSIONS: These data indicate that bipolar patients
      show a strikingly different pattern of frontal responses compared to those with
      schizophrenia and provide further evidence that abnormal frontal activation in
      psychotic disorders is more apparent during verbal fluency than semantic
      decision.

PMID- 11578664
TI  - Emotion traits in older suicide attempters and non-attempters.
AB  - BACKGROUND: Emotion is a flourishing area of cross-disciplinary research that can
      inform traditional approaches to psychopathology. The present study examines
      emotion traits associated with attempted suicide in a depressed older sample.
      METHODS: Seven emotion traits were compared in depressed inpatients, age 50 years
      or older, who either had made a suicide attempt after age 50 (n=47) or had never
      made a suicide attempt (n=38) as assessed by self-report and a review of
      available medical records. RESULTS: In univariate analyses controlled for age and
      sex, late-life suicide attempters were lower in Warmth and Positive Emotions than
      non-attempters. However, only lower Anxiety was associated with attempter status
      when all seven emotion traits were included as predictors. Of the attempters,
      those who had made a greater number of attempts reported lower Positive Emotions
      and higher Anger/Hostility and Guilt, though only lower Positive Emotions had a
      significant effect independent of the other emotions. In a subsample of 41
      patients whose index admission was precipitated by an attempt, lower
      Anger/Hostility was associated with higher intent to die, and lower
      Anger/Hostility and lower Guilt was associated with higher lethality of method.
      LIMITATIONS: The assessments of emotion traits may have been colored by transient
      moods, including, for the recent attempters, moods associated with the aftermath
      of their attempt. Participants who completed the key measures may not be
      representative of older attempters. CONCLUSIONS: Emotion traits are associated
      with suicidal behavior in older depressed patients, and the specific type of
      emotion and the direction of its association depends on the specific suicide
      variable examined. Emotion traits may be helpful in assessing suicide risk.

PMID- 11578665
TI  - Major depressive and post-traumatic stress disorder comorbidity in female victims
      of intimate partner violence.
AB  - BACKGROUND & METHODS: Victims of intimate partner violence (IPV) often develop
      psychiatric disorders. We examined the extent and correlates of comorbidity
      between two of the disorders most frequently linked to trauma--major depressive
      disorder (MDD) and post-traumatic stress disorder (PTSD)--in a group of 44 women
      who were victims of IPV within the preceding 2 years. RESULTS: MDD (68.2%) and
      PTSD (50.0%) were highly prevalent on a lifetime basis in female victims of IPV.
      On a current basis, MDD (18.2%) and IPV-related PTSD (31.8%) were more frequently
      comorbid (42.9% of cases of current IPV-related PTSD also had MDD) than would be
      expected by chance (P<0.001). Most cases of current MDD occurred in persons who
      also had current IPV-related PTSD. Severity of depressive and PTSD symptoms were
      highly correlated (r=0.84). Although women with PTSD were significantly more
      disabled than women without PTSD, persons with comorbid PTSD and MDD were not
      significantly more disabled than those with PTSD alone. LIMITATIONS: Cross
      sectional study; entry criteria for study may limit generalizability.
      CONCLUSIONS: PTSD and MDD symptoms are frequently seen in the aftermath of IPV,
      and often co-occur. The usefulness of the distinction between PTSD and MDD in
      this context remains to be determined, both in terms of diagnostic classification
      and prognostic implications.

PMID- 11578666
TI  - Untreated short-term course of major depression: a meta-analysis of outcomes from
      studies using wait-list control groups.
AB  - INTRODUCTION: While the short-term response rates to antidepressant medication
      and placebo are well established, very little is known about the short-term
      course of untreated depression. Knowledge of the course of untreated depression
      can serve as a benchmark for assessing the true benefits of active treatment.
      METHOD: A meta-analysis was performed analyzing the outcomes of all psychotherapy
      studies that randomized adult outpatients with major depressive disorder to a
      wait-list control group. RESULTS: Nineteen studies involving 221 subjects were
      reviewed. The mean decrease in Hamilton Rating Scale for Depression scores over 2
      20 weeks was 11.9%, while the mean decrease in Beck Depression Inventory scores
      was 15.7%. Using a subsample of studies that reported individual outcomes, we
      estimated that 15 of 76 subjects (19.7%) improved to a degree comparable to what
      would be considered a positive response in antidepressant trials. CONCLUSIONS: In
      the short-term, depressive symptomatology can be expected to decrease by about 10
      15% on average without treatment. As many as 20% of subjects who participate in a
      short-term antidepressant trial may experience a spontaneous remission.

PMID- 11578667
TI  - A change in the density of [(3)H]flumazenil, but not [(3)H]muscimol binding, in
      Brodmann's Area 9 from subjects with bipolar disorder.
AB  - BACKGROUND: This study examines the hypothesis that there are changes in cortical
      serotonergic, GABAergic and glutamatergic systems in bipolar disorder and
      schizophrenia. METHODS: In situ radioligand binding and autoradiography were used
      to measure neurochemical markers in Brodmann's Area (BA) 9 from control subjects
      and subjects with bipolar disorder or schizophrenia (n=8 per group). RESULTS:
      Compared to tissue from schizophrenic (mean+/-S.E.M, 385+/-44 fmol/mg ETE) and
      control (383+/-44 fmol/mg ETE) subjects, there was an increase in the density of
      [(3)H]flumazenil binding to the benzodiazepine binding site on the GABA(A)
      receptor in subjects with bipolar disorder (451+/-17 fmol/mg ETE; P<0.05). There
      was no difference in the density of [(3)H]muscimol binding to the GABA(A)
      receptor or in the density of the serotonin(1A) receptor, serotonin(2A) receptor,
      ionotropic glutamate receptors or the serotonin transporter between the three
      cohorts. There was an age-related decrease in NMDA receptor density in control
      subjects that was absent in schizophrenia and bipolar disorder. An age-related
      increase in [(3)H]flumazenil binding in schizophrenia was absent in control and
      bipolar disorder subjects. LIMITATIONS: This study involved a relatively small
      number of individuals. CONCLUSIONS: An increase in the gamma2-receptor sub-unit
      in the GABA(A) receptor has been shown to increase benzodiazepine but not
      [(3)H]muscimol binding, this is the mismatch in binding we have shown in BA 9
      from subjects with bipolar disorder. Thus, a change in the assembly of receptor
      subunits into GABA(A) receptors may be involved in the neuropathology of bipolar
      disorder. There may also be differences in age-related changes in cortical
      receptor density between bipolar disorder and schizophrenia.

PMID- 11578668
TI  - The sensitivity and specificity of the Major Depression Inventory, using the
      Present State Examination as the index of diagnostic validity.
AB  - BACKGROUND: A self-rating inventory has been developed to measure DSM-IV and ICD
      10 diagnoses of major (moderate to severe) depression by the patients' self
      reported symptoms. This Major Depression Inventory (MDI) can be scored both
      according to the DSM-IV and the ICD-10 algorithms for depressive symptomatology
      and according to severity scales by the simple total sum of the items. METHODS:
      The Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used as index
      of validity for the clinician's DSM-IV and ICD-10 diagnosis of major (moderate to
      severe) depression. The sensitivity and specificity of MDI was assessed in a
      sample of 43 subjects covering a spectrum of depressive symptoms. RESULTS: The
      sensitivity of the MDI algorithms for major depression varied between 0.86 and
      0.92. The specificity varied between 0.82 and 0.86. When using the total score of
      MDI the optimal cut-off score was estimated 26 and the total score was shown to
      be a sufficient statistic. LIMITATIONS: The sample of subjects was limited.
      Patients with psychotic depression were not included. CONCLUSION: The MDI was
      found to have a sensitivity and specificity which is acceptable. The
      questionnaire is brief and can be scored diagnostically by the DSM-IV and ICD-10
      algorithms as well as by its simple total score.

PMID- 11578669
TI  - Treatment of mood-congruent psychotic depression with imipramine.
AB  - BACKGROUND: Most studies report a poor response of psychotic depressed patients
      to treatment with a tricyclic antidepressant alone compared to combined treatment
      with an antipsychotic preparation and compared to non-psychotic depressed
      patients. However, the issue of optimal treatment of psychotic depressed patients
      has not been resolved as yet. Previously, we reported a significant difference in
      response to mirtazapine compared to imipramine in a randomised, double-blind,
      fixed-blood-level study with in-patients with major depression. In the current
      study we focus on the treatment response to imipramine in a group of patients
      with psychotic depression and compare this to patients who manifest no psychotic
      features. Our aim in presenting these findings was to contribute to the
      discussion on the optimal treatment of psychotic depressed patients. METHODS:
      Fifty-two patients with a unipolar major depression (DSM-IIIR), comprising 15
      patients with mood-congruent psychotic features and 37 patients with no psychotic
      features, were commenced on treatment with imipramine after a drug-free and
      placebo-washout period of 7 days. The dose of imipramine was adjusted for all
      patients to a predetermined blood level. The Hamilton (HRSD) and Montgomery
      Asberg (MADRS) Depression Rating Scales were used to evaluate treatment response.
      RESULTS: Of the 45 patients who completed the study, nine of the 13 psychotic
      patients (69.2%) and 14 of the 32 non-psychotic patients (43.8%) responded to
      treatment. The patients with psychotic features demonstrated a lower mean final
      HRSD score, together with a greater fall in MADRS score over time, compared to
      the non-psychotic group. Both these findings remained statistically significant
      after controlling for a number of possible confounding factors. CONCLUSIONS:
      These results demonstrate that, in this group of patients with mood-congruent
      psychotic depression, imipramine used on its own together with strict control of
      serum drug levels produced a high treatment response rate of 70%. CLINICAL
      IMPLICATIONS: If replicated, these findings suggest that imipramine with control
      of blood levels of medication may be a useful first-line treatment for depressed
      patients with mood-congruent psychotic features. LIMITATIONS: Our sample size was
      modest. This fact may caution against generalisation of the results.

PMID- 11578670
TI  - Correlates of analogue and clinical depression: a further test of the
      phenomenological continuity hypothesis.
AB  - BACKGROUND: The use of college students with high scores on a depression rating
      scale as analogues for depression by psychological researchers has generated
      controversy. Critics of analogue research argue that depression is qualitatively
      different in analogue and clinical samples. OBJECTIVE: To conduct a further
      comparison of the phenomenology of clinical and analogue depression to determine
      if the differences between these groups are best understood as quantitative
      (consistent with the continuity hypothesis) or whether these forms of depression
      are qualitatively distinct. METHOD: This study compared 161 outpatients with
      major depressive disorder to 148 "analogue" subjects (college students with a
      Beck Depression Inventory score > or =9) and 141 non-distressed controls. Study
      measures included several proposed personality vulnerability factors for
      depression, a measure of developmental experiences that may confer vulnerability
      to adult depression, and family history of emotional disorders. RESULTS: Most
      comparisons of personality vulnerability factors, developmental experiences and
      family history information followed a pattern of greatest risk in the clinical
      group, intermediate risk in the analogue group and lowest risk in the non
      distressed group. Noteworthy exceptions included several aspects of perfectionism
      and a number of childhood experiences reflecting parental over-control, which
      appeared to be more strongly associated with analogue depression than clinical
      depression. IMPLICATIONS: Several personality and developmental variables could
      represent important areas of discontinuity between clinical and analogue
      depression. However, the overall results were consistent with a growing body of
      literature suggesting continuity between subthreshold depression symptoms and
      syndromal depression.

PMID- 11578671
TI  - Bone mineral density in pre-and post-menopausal women with affective disorder
      treated with long-term L-thyroxine augmentation.
AB  - BACKGROUND: Augmentation with TSH-suppressive L-thyroxine (T4) has been shown to
      improve the course of illness in otherwise refractory affective disorders. This
      collaborative study investigates whether T4 augmentation for a minimum of 12
      months decreases bone mineral density (BMD) in 26 pre- and post-menopausal women
      with affective disorder. METHODS: We measured BMD at the femoral neck, Ward's
      triangle, trochanter and lumbar vertebrae (L1-L4) in 13 premenopausal and 13
      postmenopausal women with affective disorder using dual energy X-ray
      absorptiometry. BMD was expressed as g/cm(2) and as a Z-score, calculated using
      bone density data from the international reference population standard. RESULTS:
      The Z-scores for the pre- and post-menopausal women were within the reference
      range of the age and sex matched population standard. BMD for the composite group
      also did not differ either from the population standard. BMD in the lumbar spine
      and hip did not differ significantly between the pre- and post-menopausal groups.
      However, there were a relatively high number of postmenopausal patients with BMDs
      one S.D. lower than the population standard. LIMITATIONS: This is a cross
      sectional study with a relatively small sample size. CONCLUSIONS: The study
      demonstrates that T4 augmentation treatment does not reduce BMD to a clinically
      significant degree in many women with affective disorder. However, the resilience
      of bone structure to T4 treatment may vary with site and menopausal status. This
      study underscores the need for regular assessment of BMD during adjunctive
      thyroid treatments for affective disorder, especially in postmenopausal women.

PMID- 11578672
TI  - Depression associated with multiple sclerosis. Looking beyond diagnosis to
      symptom expression.
AB  - BACKGROUND: While it is recognised that patients with multiple sclerosis have a
      high lifetime risk for major depression, less is known about sub-syndromal
      presentations of affective instability, i.e., irritability, sadness and
      tearfulness and how these symptoms of emotional dyscontrol may affect a subject's
      overall degree of psychological distress. METHODS: A consecutive sample of 100
      out-patients with clinically definite multiple sclerosis attending their yearly
      neurological examination were assessed for major depression [Structured Clinical
      Interview for DSM-IV (SCID-1)], pathological laughing and crying [Pathological
      Laughing and Crying Scale (PLACS)], self report questionnaires documenting mood
      [Beck Depression Inventory (BDI)] and overall psychological distress [the 28 item
      General Health Questionnaire (GHQ)]. RESULTS: Seventeen percent of subjects
      received a diagnosis of major depression, 8% had pathological laughing and crying
      (PLC), 48% had symptoms of emotional dyscontrol without meeting criteria for a
      formal psychiatric diagnosis and 27% had minimal psychiatric symptoms
      (emotionally stable). The groups did not differ with respect to neurological
      variables. However, on a validated index of psychological distress (i.e., GHQ
      scores > or =5), there were significantly more subjects with major depression and
      emotional dyscontrol than those deemed emotionally stable (P<0.0001).
      LIMITATIONS: The small number of patients with PLC (N=8) curtailed statistical
      power when it came to analysing this sub-group. CONCLUSIONS: Clinicians should be
      sensitive to complaints such as irritability and sadness in patients with
      multiple sclerosis, even when symptoms do not fulfil criteria for formal,
      psychiatric diagnoses. Our data demonstrate that such complaints are associated
      with levels of psychological distress that approach those experienced by patients
      with major depression. Given that these sub-syndromes of affective instability
      respond well to pharmacotherapy, detection and treatment can significantly reduce
      one important aspect of morbidity associated with multiple sclerosis.

PMID- 11578673
TI  - Administration of antidepressants. Single versus split dosing: a meta-analysis.
AB  - OBJECTIVE: To evaluate the literature comparing antidepressant effects of
      multiple daily dosing versus single daily dosing of antidepressants. METHOD:
      Studies comparing efficacy of single versus multiple daily dosing of
      antidepressants were reviewed. Data from the clinical trials meeting our
      inclusion criteria was subgrouped according to the half-life of the
      antidepressant drug studied. Meta-analyses were carried out to compare
      antidepressant efficacy of single versus multiple daily dosing overall and
      separately for the short, intermediate, and long half life antidepressant agent
      subgroups. RESULTS: The review process identified 22 studies comparing the
      therapeutic effect of antidepressants according to their dosing schedules.
      Although most studies used antidepressant medications with short half-lives, none
      found a significant difference in therapeutic efficacy. Furthermore, the
      improvement rates in depression scores in between the two groups were almost
      identical (SDD versus MDD). CONCLUSION: This meta-analytic approach found no
      advantage for multiple daily dosing and suggests that sustained therapeutic serum
      levels are not necessary for achievement of therapeutic activity. Antidepressant
      benefit may simply require a limited duration of exposure above the threshold
      serum level. Administration of antidepressants in single daily doses appears
      sufficient to perturb the physiological pathways associated with depression
      sufficiently to achieve an adaptive therapeutic response. Moreover, a single
      daily dosing regimen offers the potential advantages of simplicity, increased
      compliance, and reduced adverse effects, which in turn would increase the overall
      success rate in treatment of depression.

PMID- 11578674
TI  - The influence of an uncaring partner on the type and outcome of depression.
AB  - BACKGROUND: We seek to clarify recent inconsistent research findings in relation
      to the Intimate Bond Measure (IBM), where low IBM care scores have been held to
      be over-represented in non-melancholic depression and to predict a poor
      depressive episode outcome. METHODS: A sample of 82 subjects meeting DSM criteria
      for a major depressive episode lasting less than 2 years, took part in a 1-year
      follow-up study. The IBM was completed at initial assessment and depression
      severity assessed at baseline and at follow-up assessment, allowing a measure of
      "outcome". RESULTS: A significantly greater proportion of DSM-defined non
      melancholic than melancholic depressives perceived their partner as providing
      deficient care and were classified as being in a dysfunctional relationship,
      seemingly unrelated to demographic differences or by depression severity,
      chronicity or recurrence. IBM scores were again established as independent of a
      number of putative distorting influences, such as depression severity and
      "neuroticism". Although the IBM failed to significantly predict outcome, there
      was a clear trend for greater improvement in those in IBM care score-defined
      "functional relationships". LIMITATIONS: The study failed to assess the change in
      patients' perceptions of care over time, which may have contributed to the
      failure to replicate past findings in relation to outcome. CONCLUSIONS: The
      significance of examining the relevance of psychosocial factors such as deficient
      intimacy to separate depressive sub-types is highlighted. Implications of these
      findings for clinical intervention and future research studies are discussed.

PMID- 11578675
TI  - Seasonal changes in 24-h patterns of suicide rates: a study on train suicides in
      The Netherlands.
AB  - BACKGROUND: Annual patterns in suicide rates, peaking near the summer solstice,
      are well documented. It has been suggested that day length or total hours of
      sunshine has an impact on suicide rates. If these environmental factors are
      involved, we would expect changes in the daily pattern of suicide rates to occur
      over the year. To test this hypothesis, the 24-h patterns of suicide rate were
      investigated as a function of time of year. METHOD: Detailed information about
      the exact time of suicides in The Netherlands is only available for train
      suicides. Therefore, information concerning age, sex, time and place of
      occurrence of all verified train suicides over 15 years in The Netherlands
      (n=2830) was obtained from The Netherlands Railways archives. RESULTS: Daily
      patterns in train suicides show systematic variations of two kinds. First,
      independently of time of year, suicide rates at night drop to about 10% of their
      daytime values. Second, there are two daily peaks in the patterns which shift
      their timing over the year, with one peak occurring shortly after sunset, and the
      other one consistently occurring 9-10 h earlier. Both peaks shift with the 5.5-h
      shift in sunset time. LIMITATIONS: Train suicidal behaviour may not represent
      fatal suicidal behaviour in general. CONCLUSIONS: There are pronounced and
      systematic daily variations in train suicide rates in The Netherlands. One of
      these is related to clock time, the others are related to the light-dark cycle.
      The consistency of the patterns suggests a strong environmental influence on
      train suicidal behaviour. Research on 24-h patterns of suicide rates should
      control for time of year.

PMID- 11578676
TI  - Early and late onset depression in old age: different aetiologies, same
      phenomenology.
AB  - BACKGROUND: Phenomenological differences between older patients with early onset
      (EO; onset of first major depressive episode before 60 years) and late onset (LO)
      depression have been inconsistent but, if real, may reflect differences in
      aetiology. We aimed to compare aetiological factors, phenomenology and cognitive
      function in older patients with depression by age of onset. METHODS: Subjects
      were all patients > or =60 years old (n=73) from 407 consecutive attenders to a
      Mood Disorders Unit, diagnosed with DSM-III-R Major Depressive Episode, at or
      close to the nadir of their episode. Putative risk factors were assessed by
      structured interview. Psychological morbidity and depressive symptoms were
      assessed by the 21-item Hamilton Rating Scale for Depression, CORE rating of
      psychomotor disturbance, Newcastle Endogeneity Scale, Zung Depression Scale and
      General Health Questionnaire. Cognition was assessed by tests of memory,
      attention, executive function and motor speed. RESULTS: Personality
      abnormalities, a family history of psychiatric illness and dysfunctional past
      maternal relationships were significantly more common in EO depression. The two
      age of onset groups were essentially similar in terms of depressive sub-type and
      severity, phenomenology, history of previous episode, and in neuropsychological
      performance. LIMITATIONS: Use of self-report data, moderate sample size, sample
      not age-matched, tertiary referral patients. CONCLUSIONS: EO and LO depression
      are similar phenotypically, but differ aetiologically. The pursuit of mechanisms
      which predispose depressive episodes may be heuristically more valuable than
      further investigation of individual depressive features in distinguishing early
      from late onset depression.

PMID- 11578677
TI  - "Side effects" of ECT are mainly depressive phenomena and are independent of age.
AB  - BACKGROUND: The aetiology of reported side effects of electroconvulsive therapy
      (ECT) is unclear. We examined the interaction of depression and age on adverse
      neuropsychological and putative side effects of ECT. METHOD: Inpatients (N=81;
      median age 70 years) with major depression were assessed prospectively pre-ECT,
      immediately post-ECT and 1-3 years later. Patients were administered the Hamilton
      Rating Scale for Depression (HRSD), the Global Assessment of Functioning scale
      (GAF) and neuropsychological tests from the Wechsler Memory Scale. Side effects
      and total burden scores were rated pre- and post-treatment. RESULTS: HRSD and GAF
      scores improved with treatment after ECT, but the prevalence and total burden of
      side effects were unchanged. Side effect burden was related to depression level
      before and after ECT. Improvement in depression correlated with reduction in side
      effect burden. There was a significant decline in side effect burden after
      controlling for change in depression. Patients' scores on neuropsychological
      measures did not appear to change after ECT or between pre-ECT and follow-up. Re
      analysis, allowing for age, chronicity of depression, medication use and
      development of dementia, did not alter the findings. LIMITATIONS: lack of a
      control group, lack of information on ECT technique, incomplete data sets and
      limited neuropsychological testing. CONCLUSIONS: ECT, an effective treatment for
      depression, does not cause significant side effects or neuropsychological
      impairment, which are more likely to be depressive phenomena. ECT appears to be
      safe for old (> or =65 years) and very old (> or =75 years) patients, who do not
      appear to be more susceptible to adverse effects.

PMID- 11578678
TI  - Use of olanzapine in dysphoric mania.
AB  - BACKGROUND: The simultaneous presentation of both manic and depressive symptoms
      has long been recognized. Nevertheless, a variable prevalence of dysphoric mania
      has been reported. The aim of this study was to estimate the prevalence of
      dysphoric mania among hospitalized patients and to assess the effectiveness of
      olanzapine in this type of patients. METHODS: Eighty-six patients who met DSM-IV
      criteria for mania were evaluated at admission with a protocol that included
      McElroy's criteria for dysphoric mania [Am. J. Psychiatry 149 (1992) 1633].
      Treatment was administered according to clinical need, using mood stabilizers
      combined with antipsychotics. Sequential assessments were conducted throughout
      the study. RESULTS: Forty-four patients (51.2%) fulfilled McElroy's criteria for
      dysphoric mania. Fourteen of these dysphoric patients were treated with
      olanzapine in combination with mood-stabilizers. All patients improved in manic
      symptoms but patients treated with olanzapine improved significantly more than
      those treated with other antipsychotics in depressive symptoms. LIMITATIONS: The
      lack of randomization is a methodological limitation of this study, so these
      findings should be considered as preliminary. CONCLUSIONS: Dysphoric symptoms are
      common in this population of manic patients. Olanzapine in combination with mood
      stabilizers may be effective in these patients. Additional controlled studies are
      needed to replicate these results.

PMID- 11578679
TI  - Lower self-reported depression in patients with erectile dysfunction after
      treatment with sildenafil.
AB  - BACKGROUND: Depressive symptoms in men with erectile dysfunction (ED) may improve
      under successful ED treatment. Self-reported depressive symptoms were compared in
      men with ED after sildenafil treatment to a group of untreated patients. METHODS:
      In an open study, self-reported depressive symptoms of 54 men after successful
      treatment with sildenafil (>4 weeks) and 51 men awaiting ED treatment were
      investigated with the Center of Epidemiologic Studies-Depression Scale (CES-D).
      CES-D items were subjected to an exploratory factor analysis and group
      differences in CES-D items and factors were analyzed. RESULTS: Groups were
      comparable with respect to demographic characteristics and illness duration. CES
      D total scores were lower in the group treated with sildenafil. Substantial
      differences were found in favor of the group treated with sildenafil,
      particularly in scores on a "positive affect" factor. CONCLUSIONS: The findings
      emphasize the relevance of depression associated with ED and the importance of
      effective ED treatment. Although depression was generally low in this sample,
      hedonistic aspects were substantially enhanced in the group of ED patients after
      sildenafil treatment. LIMITATIONS: The open and cross-sectional study design does
      not permit causal inference. Selection bias and motivational aspects to
      participate in the study can not completely be ruled out.

PMID- 11578680
TI  - Affective symptoms at index hospitalization in childhood and depressive symptoms
      in adulthood: a "catch-up" study.
AB  - PURPOSE: To analyze whether affective symptoms during psychiatric treatment in
      childhood or adolescence could predict the later development of depressive
      symptoms. METHOD: We used a "catch-up" design. A cohort of former child and
      adolescent psychiatric patients was assessed in adulthood with standardized
      instruments according to the criteria of ICD-10 (SCAN) and dimensional values for
      depression (both self-reported and observer-rated). Initial affective symptoms
      had been extracted from clinical records according to a standardized system
      (AMDP). RESULTS: We assessed 164 former patients. Twelve percent of these
      fulfilled diagnostic criteria of an affective disorder (F3) according to ICD-10.
      In univariate analyses of variance the depression scores were significantly
      related to affective symptoms during childhood treatment, even if the presence of
      an affective disorder at catch-up was considered as an independent covariate
      variable. Nevertheless, the latter variable explained a large part of the
      variance of depression scores, while initial affective symptoms explained no more
      than 6%. CONCLUSION: Affective symptoms in childhood and adolescence may predict
      the later development of subthreshold depressive symptomatology.

PMID- 11578681
TI  - A 3.5-year naturalistic follow-up study of depressed out-patients.
AB  - Outcome studies of patients suffering from depression indicate high relapse rates
      and a tendency towards chronicity. The present study describes the long-term
      outcome of 95 depressed outpatients in a third-level referral centre. and
      examines the relationship between baseline-variables (age, sex, level of
      psychopathology, age at onset of first psychiatric disorder, duration of illness
      at baseline, diagnosis) and outcome variables. After 3.5 years, 34 patients (36%)
      had a chronic course, 24 patients (25%) had at least one recurrence and 37
      patients (39%) had a non-recurrent course. Chronicity was significantly
      correlated with an early age of onset of the first psychiatric disorder, a high
      level of psychopathology and a high level of depressive symptoms at baseline. The
      duration of depression at index did not differentiate chronic course from
      recurrent or non-recurrent course. After 1 year of follow-up, patients with
      recurrence were significantly more likely to stop antidepressant treatment. The
      results confirm the great chance for chronicity and recurrence in depression and
      the need to develop long-term treatment programs to prevent relapse.

PMID- 11578682
TI  - Effect of ethinyl estradiol on the panic response to the panicogenic agent
      pentagastrin.
AB  - BACKGROUND: Panic disorder (PD) symptomatology has been reported to be altered by
      hormonal events or treatments which affect estrogen levels. Coryell et al. [Arch.
      Gen. Psychiatry, 39 (1982) 701-703; Am. J. Psychiatry, 143 (1986) 508-510] have
      suggested that the increased cardiovascular risk associated with PD is
      significantly greater in males, alluding to a potential cardioprotective effect
      of female hormones in the context of panic attacks. In the present study, we
      were, therefore, interested in elucidating the role of estrogen in modulating the
      behavioural and cardiovascular responses induced by the panicogenic agent
      pentagastrin, a cholecystokinin-B (CCK(B)) receptor agonist. METHODS: A double
      blind cross-over placebo-controlled design with randomization of the order of a 3
      day pretreatment of ethinyl estradiol (EE) (50 microg/day) or placebo was used to
      assess the effect of a 30-microg i.v. bolus injection of pentagastrin on panic
      symptom intensity and on increases in heart rate (DeltaHR), systolic (DeltaSBP)
      and diastolic (DeltaDBP) blood pressure following each pretreatment. Subjects
      were 9 male healthy controls and 11 male PD patients. RESULTS: EE pretreatment
      did not significantly reduce the pentagastrin-induced panic symptom scale (PSS)
      scores and had no effect on DeltaDBP or DeltaSBP. EE did, however, attenuate the
      pentagastrin-induced increase in HR in both PD patients and healthy controls.
      LIMITATIONS: Only male subjects were included in the present study; however, we
      are currently investigating the influence of female gonadal hormones on the panic
      response to pentagastrin in female PD patients and healthy controls. CONCLUSION:
      Our results suggest that estrogens may display cardioprotective effects in the
      context of panic attacks.

PMID- 11578683
TI  - Fact or artifact--a comment on "Subpopulations of early separation anxiety:
      relevance to risk of adult anxiety disorders".

PMID- 11578684
TI  - Dendritic cells: their significance in health and disease.
AB  - Dendritic cells (DCs) represent a heterogeneous population of professional
      antigen-presenting cells. Precursor cells move via the blood to peripheral
      tissues. These immature DCs can take up invading pathogens and then rapidly
      migrate to the draining secondary lymphoid organs. Converted into antigen
      presenting mature DCs, these cells are able to prime naive T cells and to
      initiate an adoptive immune response. The extraordinary functional profile
      suggests that, under certain preconditions, DCs may represent an ideal vector in
      the immunotherapy of cancer and infectious diseases

PMID- 11578685
TI  - Serum L-selectin and ICAM-1 in patients with Graves' ophthalmopathy during
      treatment with corticosteroids.
AB  - Circulating forms of L-selectin were found to be elevated in several autoimmune
      diseases. ICAM-1 has been suggested a predictor of the onset of GO. The aim of
      the study was an estimation of serum L-selectin and ICAM-1 in patients with
      Graves' disease with ophthalmopathy during treatment with corticosteroids to
      assess their potential as a guideline of immunosuppressive therapy. We detected
      serum L-selectin and ICAM-1 in three groups of subjects: 20 patients with Graves'
      disease without ophthalmopathy (Gd), 17 patients with clinical symptoms of
      ophthalmopathy (CAS> or =3, anamnesis of GO> or =1 year) and 24 healthy
      volunteers. Corticosteroid therapy consisted of intravenous infusions of
      methyloprednisolone (MP) and subsequent treatment with oral prednisone (P). The
      serum samples were collected 24 h before MP, 24 h after MP, 12+/-2 days of
      treatment with prednisone and after the end of the corticosteroid therapy. The
      levels of soluble L-selectin and ICAM-1 in the serum were determined by the ELISA
      method. The statistical significance was estimated by the Mann-Whitney U-test.
      Serum L-selectin and ICAM-1 were significantly increased in patients with GO
      (respectively 1182+/-222 and 438+/-68 ng/ml) and in patients with Graves' disease
      without ophthalmopathy (respectively: 1168+/-130 and 343+/-109) in relation to
      the controls. After MP treatment in corticosteroid-responsive patients
      (improvement in CAS < or =1) serum concentration of L-selectin and ICAM-1
      decreased significantly and gradually increased during subsequent treatment with
      prednisone. In corticosteroid-responsive patients serum L-selectin was
      significantly higher before MP administration and after P treatment in relation
      to corticosteroid-resistant subjects. CONCLUSIONS: 1. Serum L-selectin and ICAM-1
      were elevated in patients with active GO 2. Methyloprednisolone decreased levels
      of the studied adhesion molecules in corticosteroid-responsive patients with GO
      3. Lack of clinical results in corticosteroid therapy in patients with a low
      starting L-selectin level would suggest the possibility of serum L-selectin
      estimation as a prognostic for immunotherapy efficacy.

PMID- 11578686
TI  - Endogenous Trypanosoma cruzi Tc52 protein expression upregulates the growth of
      murine macrophages and fibroblasts and cytokine gene expression.

PMID- 11578687
TI  - Humoral immune response to cruzipain and cardiac dysfunction in chronic Chagas
      disease.
AB  - The humoral immune response to epitopes expressed on cruzipain was evaluated in
      31 Chagas disease patients (CDP) with different degrees of cardiac dysfunction.
      We took advantage of the availability of anti-Trypanosoma cruzi microsomal
      fraction monoclonal antibodies (MoAbs) reactive with epitopes that are recognized
      (5A9B11) or not recognized (1A10C11) by CDP sera. The 5A9B11- and 1A10C11-like
      epitopes are expressed on cruzipain. The reactivity of 5A9B11 against cruzipain
      was completely inhibited by sera of severe cardiopathy patients while a partial
      inhibition was found with sera from chagasic patients with mild disease. CDP sera
      did not block cruzipain recognition by 1A10C11. The antigenic determinants
      recognized by CDP sera appeared to be linear and carbohydrate free. When the
      overall anti-cruzipain immune response was evaluated, 70% of CDP with severe
      disease showed cruzipain titers higher than 1/800 while none of them displayed
      titers lower that 1/400. This report shows for the first time that the humoral
      immune response against epitopes expressed on cruzipain appeared to be related
      with the severity of chronic Chagas disease.

PMID- 11578688
TI  - Immunisation with phage-displayed variable region 2 from meningococcal PorA outer
      membrane protein induces bactericidal antibodies against Neisseria meningitidis.
AB  - The immunogenicity and functional activity of antibodies raised in mice against
      the cyclic disulphide peptide corresponding to the variable region 2 of PorA
      outer membrane protein from Neisseria meningitidis strain B385 (serosubtype
      P1.15), displayed on filamentous phage, were evaluated. The epitope, flanked
      either by cysteine or cysteine and three glycine residues, was expressed as a
      fusion to PVIII protein from M13. Immunisation of Balb/C mice with either phage
      generated antibody specific responses. Sera raised against the phage exposing the
      cyclic peptide through the three-glycine linker recognised the native protein
      better than those raised against the peptide with no linker. Only the phage
      displaying the cyclic peptide with linker was capable of inducing antibodies with
      bactericidal activity. These results indicate the possibility of using phage
      display for conformational peptide expression for immunisation to elicit
      functional antibody responses.

PMID- 11578689
TI  - Association of B lymphocyte antigen receptor polypeptides with multiple chaperone
      proteins.
AB  - The B cell antigen receptor (BCR) is comprised of four different polypeptides,
      immunoglobulin (Ig) heavy chain, Ig light chain, and the two signaling subunits
      of this receptor, Ig-alpha and Ig-beta. These four chains must assemble correctly
      in the endoplasmic reticulum (ER) before the BCR can be transported to the cell
      surface. The roles of the different chaperone proteins in mediating the assembly
      of mIg with the Ig-alpha/beta are not fully understood. To gain insights into the
      roles of chaperone proteins in BCR assembly, we have generated transfected non
      lymphoid cell lines that express various intermediate assembled forms of the BCR
      and used them to examine the interactions of chaperone proteins with subunits of
      the BCR. We examined the interactions of BiP (GRP78), GRP94 and calnexin with the
      mu heavy chain, lambda light chain, Ig-alpha and Ig-beta. We report for the first
      time that Ig-alpha associates with GRP94 and that this interaction increases
      dramatically when other BCR chains are co-expressed. In contrast, the mu heavy
      chain interacts strongly with BiP (GRP78) when expressed by itself but this
      interaction is reduced when the lambda light chain is expressed, with the
      resulting mu(lambda) complexes interacting with GRP94 and calnexin. Thus, our
      data are consistent with the idea that there is an ordered association of BCR
      components with different protein chaperones during BCR assembly.

PMID- 11578691
TI  - Monocyte-dependent cell death of T lymphocyte subsets in chronic hepatitis C.
AB  - A high incidence of viral persistence and progression to chronic hepatitis are
      characteristic features of hepatitis C virus (HCV) infection. Since T lymphocytes
      play a critical role in virus clearance, their abnormalities in undergoing
      apoptosis may cause the insufficient antiviral immune responses leading to
      persistent viral infection. Recent reports have suggested that monocyte-dependent
      cell death (MDCD) is a mechanism of T lymphocyte apoptosis in chronic viral
      infection. The current study was designed to monitor apoptosis of CD4+ and CD8+ T
      lymphocyte subsets in co-culture with CD14+ monocytes under the apoptotic stimuli
      in patients with chronic hepatitis C. Cell mortalities of CD4+ and CD8+ T
      lymphocyte subsets from patients exhibiting various degrees of chronic hepatitis
      C were increased to a greater extent when incubated with CD14+ monocyte subset in
      medium containing phorbol 12-myristate 13-acetate. The current observations
      demonstrate that MDCD of CD4+ and CD8+ T lymphocyte subsets may provide a
      cellular basis for immune dysfunction which results in insufficient viral
      clearance and progression of liver disease in chronic HCV infection.

PMID- 11578690
TI  - Humoral immune response directed against LEDGF in patients with VKH.
AB  - Vogt-Koyanagi-Harada disease is an autoimmune systemic disorder. In Vogt-Koyanagi
      Harada disease, inflammatory disorders occur in multiple organs containing
      melanocytes, including uvea (resulting in acute bilateral panuveitis), skin
      (resulting in vitiligo and alopecia), central nervous system (resulting in
      meningitis) and inner ears (resulting in hearing loss and tinnitus). These
      inflammatory aspects are attributed to the destruction of melanocytes through
      immunological mechanisms. Studies have been carried out to elucidate the exact
      etiology and target autoantigen in Vogt-Koyanagi-Harada disease, but much remains
      to be investigated. Identification of target autoantigen is important to
      understand the etiology of autoimmune diseases, and for development of antigen
      specific immuno-modulation therapy. To identify the target autoantigens in Vogt
      Koyanagi-Harada disease, we made use of an immunoscreening of a bovine uveal cDNA
      expression library with serum samples obtained from patients with Vogt-Koyanagi
      Harada disease. We identified an immunoreactive cDNA clone that encodes bovine
      lens epithelium derived growth factor. mRNA of human lens epithelium derived
      growth factor was determined by reverse transcription-polymerase chain reaction
      and it was expressed in human uvea, retina and melanocytes. Immunoglobulin G
      (IgG) autoantibodies were quantitated in an enzyme-linked immunosorbent assay,
      using recombinant human lens epithelium derived growth factor. The prevalence of
      IgG anti-lens epithelium derived growth factor autoantibodies in patients with
      Vogt-Koyanagi-Harada disease was significantly higher than that in healthy
      controls (66.7% versus 21.6%, P<0.001). On the other hand, the prevalence of the
      autoantibody in patients with panuveitis of other etiology, Behcet's disease and
      sarcoidosis, was almost same as that in healthy controls. These results suggest
      that the humoral immune response agonist lens epithelium derived growth factor is
      not a mere secondary phenomena caused by uveal tissue damage.

PMID- 11578692
TI  - Peptide-based analysis of amino acid sequences important to the biological
      activity of eosinophil granule major basic protein.
AB  - Synthetic peptides corresponding to amino acid sequences in eosinophil granule
      major basic protein (MBP) were evaluated for cytotoxic activity toward K562 cells
      and for ability to stimulate basophil mediator release. Results obtained using 14
      peptides spanning the 117-amino acid sequence of MBP in overlapping fashion
      indicated that the activities mapped to peptide sequences near the amino and
      carboxy termini of MBP. The activity of these regions was confirmed using two
      peptides corresponding to MBP residues 18-45 and 89-117. A 20-h incubation with 5
      microM peptide 18-45 or peptide 89-117 caused approximately the same levels
      (>60%) of cytotoxicity in K562 cells as 5 microM MBP. Similarly, a 30-min
      incubation with peptides 18-44 and 89-117 stimulated basophil histamine release
      in a concentration-dependent manner over the range of 5-20 microM. The level of
      release stimulated by 20 microM peptide 89-117 approached that stimulated by 2
      microM MBP. A 20 microM concentration of peptide 89-117 also stimulated
      leukotriene C4 (LTC4) production by the basophils. Neither peptide 18-45 nor
      peptide 89-117 was cytotoxic for basophils under the experimental conditions for
      histamine and LTC4 release, as determined by 51Cr release. These results indicate
      that two MBP peptide sequences, including one (89-117) that contains a unique
      carbohydrate-binding region, share the biologic activities of MBP.

PMID- 11578693
TI  - Serum and cerebrospinal fluid soluble Fas levels in clinical subgroups of
      multiple sclerosis.
AB  - Elevated sFas levels have been described in multiple sclerosis (MS) patients with
      active disease. The aim of this study was to assess the diagnostic potential of
      serum and cerebrospinal fluid (CSF) sFas measurements in differentiating
      clinically defined MS patient subgroups. Levels of sFas and sFas indices were
      determined in patients with stable relapsing-remitting MS (RRMS), active RRMS,
      primary progressive MS (PPMS), secondary progressive MS (SPMS) and patients with
      inflammatory (IND) and noninflammatory neurological diseases (NIND). Serum sFas
      modulation over 32 weeks IFN-beta1a therapy was also investigated. Serum and CSF
      sFas levels and sFas indices were elevated in MS compared to NIND and IND
      patients. Within the MS group, serum and CSF sFas levels were highest in PPMS,
      with active RRMS patients demonstrating the highest sFas indices. This may
      reflect an ongoing disease process which is occurring acutely (active disease) or
      incessantly (progressive disease). IFN-beta1a induced a transient increase in
      circulating sFas following initiation of therapy. Whilst evidence was provided
      for variable sFas expression in clinical subgroups of MS, there was insufficient
      definition between the respective groups to advocate sFas measurements as a
      diagnostic marker of clinical subgroups of MS.

PMID- 11578694
TI  - Involvement of pp125FAK and p60SRC in the signaling through Fc gamma RII-Fc gamma
      RIII in murine macrophages.
AB  - Cross-linking the FcgammaRs can activate a wide variety of biological responses
      in macrophages. Receptor stimulation induces activation of protein tyrosine
      kinase cascades that result in phagocytosis, a process known to involve
      cytoskeletal rearrangements. Therefore, an involvement of non-receptor tyrosine
      kinases such as pp125FAK, in FcgammaR signaling is likely. Using the murine
      macrophage cell line J774, we demonstrate that FcgammaRII-RIII cross-linking
      induces a time- and dose-dependent increase in tyrosine phosphorylation of the
      focal adhesion kinase pp125FAK that correlates with an increase in its catalytic
      activity. Interestingly enough, pp125FAK activation results in its association
      both to the FcgammaRII-III and to p60Src. The results presented here define a
      novel-signaling pathway likely to be important in low affinity FcgammaRII-III
      mediated phagocytosis.

PMID- 11578695
TI  - Deletion of N-terminal myristoylation site of HIV Nef abrogates both MHC-1 and
      CD4 down-regulation.
AB  - HIV-1 Nef is a desirable vaccine component because it is expressed early and
      abundantly during HIV infection, and contains many CTL, T-helper cell, and B-cell
      epitopes. Nef, however, down-regulates MHC-1 and CD4 cell surface expression,
      contributing to viral escape from host immunity. To prevent Nef from down
      regulating both MHC-1 and CD4 while preserving most CTL epitopes, a panel of Nef
      mutants was constructed and assessed. Some mutants, as expected, modulated either
      MHC-1 or CD4 expression. Others prevented down-regulation of both proteins but
      sacrificed numerous immunogenic epitopes. Deletion of 19 N-terminal amino acids
      including the myristoylation signal from Nef completely abrogated both MHC-1 and
      CD4 down-regulation while preserving most CTL, T-helper and B-cell epitopes. Our
      results demonstrate that the myristoylation signal in the Nef protein is critical
      for Nef-mediated endocytosis of both MHC-1 and CD4. Non-myristoylated Nef
      containing a full complement of CTL epitopes has greater potential as a vaccine
      component than wild-type Nef.

PMID- 11578696
TI  - Thymic epithelial cells induce Fas-independent activation apoptosis of
      thymocytes.
AB  - Co-cultivation of human thymocytes with homologous thymic epithelial cells (TEC)
      resulted in apoptosis of thymocytes and increase of CD25 expression. TEC
      supernatant also induced these effects. Fraction of apoptotic cells was enriched
      by CD69+ cells but not by CD95+ cells. Thymocytes of mice MRL-lpr/lpr bearing
      mutant form of gene Fas were sensitive to apoptosis induction in co-culture with
      TEC in the same degree as thymocytes of mice bearing Fas gene of wild type.
      Apoptosis of murine thymocytes can be induced by co-cultivation with both murine
      and human TEC.

PMID- 11578697
TI  - Altered immunophenotype of dendritic cells generated from HIV infected subjects.

PMID- 11578698
TI  - Cardiovascular genomics has taken flight.

PMID- 11578699
TI  - Chemokines: the link between inflammation, restenosis and atherosclerosis?

PMID- 11578700
TI  - Impact of low level laser irradiation on infarct size in the rat following
      myocardial infarction.
AB  - Low energy level irradiation (LLLI) has been found to modulate biological
      processes. The effect of LLLI on the development of acute myocardial infarction
      (MI) was investigated following chronic ligation of the left anterior descending
      (LAD) coronary artery in laboratory rats. The hearts of 22 rats were laser
      irradiated (LI) using a diode laser (804 nm, 38 mW power output) through the
      intercostal muscles in the chest following MI and on day 3 post MI. In the
      control non laser irradiated (NLI) group (19 rats) MI was induced experimentally
      and laser irradiation was not applied. All rats were sacrificed 21 days post MI.
      Size, thickness and relative circumferential length of the infarct, as well as
      other parameters, were determined from histological sections stained with
      Masson's trichrome and hearts stained with triphenyl tetrazolium chloride (TTC)
      using histomorphometric methods. The infarct size (expressed as percent of total
      left ventricle area) of the LI rats was 10.1+/-5.8, which was significantly lower
      (65%; P<0.01) than the infarct size of NLI rats which was 28.7+/-9.6.
      Correlatively, the ratio of circumferential length of the infarcted area was
      significantly lower (2-fold; P<0.01) in the LI rats as compared to the NLI rats.
      LLLI of the infarcted area in the myocardium of experimentally induced MI rats,
      at the correct energy, duration and timing, markedly reduces the loss of
      myocardial tissue. This phenomenon may have an important beneficial effect on
      patients after acute MI or ischemic heart disease.

PMID- 11578702
TI  - Coronary arteriographic findings in symptomatic and asymptomatic subjects with
      coronary artery calcification.
AB  - The relation of coronary artery calcification with the presence of symptoms of
      coronary artery disease and its angiographic severity is not clear. We studied 37
      apparently healthy, asymptomatic subjects that were found by digital
      cinefluoroscopy to have coronary calcium and compared to age- and sex-matched
      group of patients with coronary calcium and symptomatic coronary artery disease.
      Normal coronary arteries and non-obstructive lesions only were found in 12/37
      (32.4%) and 11/37 (29.7%) asymptomatic subjects vs. 1/37 (2.7%) and 2/37 (5.4%)
      patients; P<0.001 and P<0.012, respectively. Obstructive lesions were more rare
      in asymptomatic subjects than in patients, 14/37 (37.8%) vs. 34/37 (91.9%)
      (P<0.0001), as well as total occlusions, 2/37 (5.4%) vs. 10/37 (27%) (P<0.024).
      Median worst lesion stenosis was 30% in asymptomatic subjects and 95% in patients
      (P<0.0001). In asymptomatic usual cardiovascular risk subjects, coronary calcium
      detection by digital cinefluoroscopy is accompanied by a relatively high
      probability of obstructive disease, although less severe angiographically than in
      age- and sex-matched catheterized patients with symptomatic coronary artery
      disease.

PMID- 11578704
TI  - Assessment of cardiac risk before peripheral vascular surgery: a comparison of
      myocardial perfusion imaging and long axis echocardiography at rest.
AB  - OBJECTIVE: To compare resting long axis echocardiography with adenosine thallium
      201 emission tomography in detecting myocardial ischaemic abnormalities and
      surgical related risk in patients before peripheral vascular surgery. DESIGN: A
      prospective and blinded pre-operative examination of resting left ventricular
      minor and long axes and myocardial perfusion during adenosine vasodilation using
      thallium-201 emission tomography. SETTING: A tertiary referral centre for cardiac
      and vascular disease equipped with invasive, non-invasive and surgical
      facilities. SUBJECTS: 65 patients (40 male) with significant peripheral vascular
      disease, mean age 63+/-10 (S.D.) years, and 21 normal subjects of similar age.
      RESULTS: Thallium-201 myocardial perfusion tomography was abnormal in 50/65
      patients; 27 had fixed, 23 reversible abnormalities (19 of whom had both). Long
      axis was considered abnormal if one or more of two systolic long axis
      disturbances, reduced extent of total excursion <1 cm at any of the three (left,
      septal and posterior left ventricular) sites or prolonged shortening >1 mm after
      A2, and two diastolic abnormalities, delayed onset of lengthening >80 ms after A2
      or reduced peak lengthening velocity <4.5 cm/s, was present. Long axis score
      (maximum 12) was based on the presence or absence of these four disturbances at
      each of the three sites. Myocardial perfusion imaging with thallium-201
      classified the patients into three different groups according to their liability
      to low, moderate or high surgical risk (summed stress perfusion score of 36).
      Thirteen of 50 patients were identified as subjects at high surgical risk, with a
      perfusion score of 22/36 and below. Twelve of these demonstrated significantly
      greater impairment of systolic and diastolic long axis function, compared to
      those at low surgical risk, with a total long axis echo score of 6/12 or more.
      Seventeen of 18 patients identified as being at low surgical risk, with a
      perfusion score of 32/36 and above, had total long axis score of less than 6/12.
      The remaining 19 moderate risk patients had a wide range of long axis scores. In
      the 65 patients studied there were two post-operative deaths, one post-discharge
      death due to cerebrovascular accident, and one due to renal failure. CONCLUSION:
      The combination of both systolic and diastolic long axis disturbances in patients
      with peripheral vascular disease can be used to predict the thallium assessment
      of surgical risk. Long axis echocardiography may thus have value as a screening
      test before non-cardiac surgery as well as providing a means of monitoring
      myocardial perfusion.

PMID- 11578706
TI  - Activation of CD14 on circulating monocytes in patients with acute coronary
      syndrome.
AB  - BACKGROUND: Increasing evidence supports the involvement of inflammation in acute
      phase of coronary artery diseases. METHODS: We analyzed the status of activation
      of inflammatory cells in 38 patients with acute coronary syndrome, 14 stable
      angina patients, and 19 control subjects by flow-cytometry. Expression levels of
      CD14 and the percentage of HLA-DR(+) T-lymphocytes were used as markers of
      monocyte and T-lymphocytes activation, respectively. RESULTS: The expression of
      CD14 on monocytes in acute coronary syndrome patients (mean fluorescence
      intensity+/-S.D.=158.1+/-77.1) was increased significantly in comparison to
      control subjects (57.1+/-8.0) and the stable angina group (63.6+/-22.0) (P<0.0001
      for both). A significantly higher percentage of HLA-DR positive T-lymphocytes
      (20.4+/-9.0 vs. 12.7+/-3.7%, P<0.01) was observed in acute coronary syndrome
      patients in comparison to control subjects. Incubation of whole blood cells with
      bacterial lipopolysaccharide resulted in a 2.4-fold higher secretion of tumor
      necrosis factor-alpha in acute coronary syndrome patients than in control
      subjects (P<0.05). When these markers of activation were measured in acute
      coronary syndrome patients 6 weeks after medical treatment, a significant
      reduction both in monocytic CD14 expression and percentage of HLA-DR positive T
      lymphocytes (P<0.05 for both) was observed. DISCUSSION: We observed markedly
      increased levels of monocytic CD14 expression in ACS patients, which appear to
      indicate the activated status of monocytes and hyper-responsiveness to external
      stimuli. The CD14 expression levels decreased as the patients were treated,
      indicating that the expression of CD14 accurately represents the activation
      status of monocytes during the acute phase of coronary artery diseases.

PMID- 11578707
TI  - Experiences with iohexol and iodixanol during cardioangiography in an unselected
      patient population.
AB  - AIM: To compare the frequency of adverse events after cardioangiography with
      iohexol and iodixanol in an unselected patient population with special regard to
      previously defined "risk patients": age> or =65 years, severe coronary artery
      disease, unstable angina pectoris and left ventricular dysfunction. METHODS: A
      total of 1020 patients referred to cardioangiography were included in this open,
      prospective cross-sectional study, comparing iodixanol (320 mgI/ml) and iohexol
      (350 mgI/ml). Adverse events were recorded and the patients answered a
      questionnaire. RESULTS: Cardiac adverse events (CAE) i.e., angina pectoris,
      arrhythmia and dyspnea within 24 h of examination were reported by 9% of patients
      receiving iohexol and by 7% receiving iodixanol. Two cases of ventricular
      fibrillation occurred, both after iohexol. The proportion of CAE was 11% for
      patients> or =65 years receiving iohexol and 7% in younger patients. For patients
      receiving iodixanol the proportion was 7%, in both age groups. Patients with
      severe coronary disease had more CAE than less ill patients in both CM groups.
      The proportion of unstable patients with CAE was 18% in the iohexol group and 12%
      in the iodixanol group. Left ventricular dysfunction was not related to CAE.
      CONCLUSIONS: Iodixanol could be advantageous in patients with unstable angina.

PMID- 11578708
TI  - Dynamic change in collateral flow associated with myocardial ischemia in humans.
AB  - BACKGROUND: This study sought to investigate how collateral flow changes during
      myocardial ischemia in patients. METHODS: Myocardial contrast echocardiography
      (MCE) and rapid atrial pacing were performed in 20 patients with angiographically
      evidenced coronary collaterals from the right coronary artery (RCA) to the
      occluded left anterior descending coronary artery. Sonicated contrast medium was
      injected into the RCA before and immediately after atrial pacing to determine the
      peak background-subtracted contrast intensity (PI) in the collateral territory
      (PIA) and its ratio to PI in the control territory (PI ratio) as parameters of
      collateral blood flow. Lactate production in the coronary circulation during
      pacing was determined to assess myocardial ischemia in the collateral territory.
      RESULTS: PIA showed a significant correlation with regional wall motion either
      before (r(squared)=-0.64, P<0.01) or after pacing (r(squared)=-0.65, P<0.01).
      Similarly, PI ratio was significantly correlated with regional wall motion either
      before (r(squared)=-0.54, P<0.05) or after pacing (r(squared)=-0.64, P<0.01).
      Rapid atrial pacing decreased both PIA and PI ratio significantly greater in
      patients with lactate production than in those without (PIA: -67+/-53 vs. -15+/
      34%, P<0.05; PI ratio: -68+/-49 vs. -8.2+/-32%, P<0.05, respectively), while
      neither PIA nor PI ratio differ between the two groups of patients before pacing
      (PIA: 13.8+/-19. vs. 16.2+/-13.3U, P=0.75; PI ratio: 0.70+/-0.71 vs. 0.87+/-0.65,
      P=0.58, respectively). CONCLUSIONS: We concluded that (1) collateral flow
      determined by MCE was closely associated with regional cardiac function, and (2)
      not the amount of collateral flow at rest, but pacing-induced change of
      collateral flow seemed to be a determinant of regional ischemia in patients with
      coronary collaterals.

PMID- 11578709
TI  - Molecular genetics and gene expression in atherosclerosis.
AB  - Although molecular cardiology is a relative young discipline, the impact of the
      new techniques on diagnosis and therapy in cardiovascular disease are extensive.
      Our insight into pathophysiological mechanisms is rapidly expanding and is
      changing our understanding of cardiovascular disease radically and irrevocably.
      Molecular cardiology has many different aspects. In this paper the importance of
      molecular cardiology and genetics for every day clinical practice are briefly
      outlined. It is expected that in the genetic predisposition for atherosclerotic
      disease multiple genes are involved (genetics). The role of only a minority of
      genes involved in the atherosclerotic process is known. Far less is known about
      particular gene-gene and gene-environment interactions. In some families disease
      can be explained mostly by a single, major gene (monogenic), of which the lipid
      disorder Familial Hypercholesterolemia is an example. In other cases, one or
      several variations in minor genes (multigenic) contribute to an atherosclerotic
      predisposition, for instance the lipoprotein lipase gene. Although mutations in
      this gene influence lipoprotein levels, disease development is predominantly
      depending on environmental influences. Recently several additional genetic risk
      factors were identified including elevated levels of lipoprotein (a) [Lp(a)], the
      DD genotype of angiotensin converting enzyme (ACE), and elevated levels of
      homocysteine. This illustrates the complexity of genetics in relation to
      atherosclerosis and the difficulty to assign predictive values to separate
      genetic risk factors. Furthermore, little attention has been given to protective
      genes thus far, explaining why some high risk patients are protected from
      vascular disease. Genetics based treatment or elimination of the genetic risk
      factor requires complete understanding of the pathogenic molecular basis. Once
      this requirement is fulfilled, disease management can be strived for, provided
      that adequate medical management is available. Recent studies suggest that such
      treatment should be genotype specific, as the genetic makeup can determine the
      outcome of a pharmacological intervention (pharmacogenetics). Once the trigger
      for atherosclerosis has initiated disease development, various genes are
      activated or silenced and contribute to lesion progression. Every stage of lesion
      development depends on a different gene expression programme (genomics). In this
      review paper an introduction is provided into genetics, pharmacogenetics and gene
      expression with respect to atherosclerotic disease.

PMID- 11578710
TI  - Immediate and long-term outcomes of stent implantation for unprotected left main
      coronary artery disease.
AB  - Left main coronary artery (LMCA) disease is now uniformly treated with coronary
      artery bypass grafting (CABG). However, some patients with LMCA disease do not
      receive CABG because of high operative risks. The advent of stent implantation
      has permitted a non-operative improvement in myocardial blood flow in many
      patients with single- and multi-vessel coronary artery disease. However, the
      outcomes of stent implantation for unprotected LMCA disease are still unclear.
      Stent implantation was performed for unprotected LMCA disease in 13 patients;
      eight patients had high operative risk and five patients had refused CABG. The
      primary success rate was 100% (13/13 patients). One patient (8%) developed a non
      Q-wave myocardial infarction after LMCA stenting. Repeat angiography was obtained
      in five patients (38%) with recurrent angina, and three patients (23%) received
      repeated percutaneous transluminal coronary angioplasty (PTCA) for LMCA
      restenosis. In the follow-up period of 18+/-3 months, 12 patients (92%) remained
      in satisfactory condition with no further need for surgical intervention. One
      patient (8%) ultimately required CABG, and she died after CABG at 3 months after
      LMCA stenting. In conclusion, although CABG remains the standard treatment for
      LMCA disease, the present study demonstrates that stent implantation is a safe
      and clinically beneficial revascularization procedure for unprotected LMCA
      disease in patients who have high operative risk as well as those who refuse
      CABG.

PMID- 11578711
TI  - QT interval effects of cisapride in the clinical setting.
AB  - PURPOSE: The clinical effect of cisapride on QT intervals was prospectively
      studied. SUBJECTS: Consecutive adult patients were recruited in whom cisapride
      was indicated for gastroesophogeal reflux, gastric ulcer, duodenal ulcer,
      diabetic gastroparesis or chronic constipation refractory to laxatives. Exclusion
      criteria included disorders and medications affecting cardiac conduction,
      electrolyte homeostasis, drug clearance and membrane stability. METHODS: Seventy
      five patients were included and followed at 1 to 2 week intervals. Patients took
      cisapride 5 mg thrice daily for 1 to 4 weeks (lower dose stage), followed by 10
      mg thrice daily for another 1 to 4 weeks (higher dose stage). Twelve-lead ECGs
      were performed before commencing cisapride (group B), at completion of the lower
      dose stage (group L) and at completion of the higher dose stage (group H).
      RESULTS: No patients experienced presyncope or syncope. Seventeen patients
      failing to comply, and 7 complaining of abdominal discomfort or diarrhea were
      excluded, leaving 51 participants. Group H's corrected QT interval (QTc) was
      longer than group B's by 13+/-15 ms (P<0.001), and longer than group L's by 7+/
      11 ms (P<0.001). Group L's QTc was longer than group B's by 7+/-21 ms (P<0.05).
      QT dispersion did not differ significantly among groups. Neither torsade de
      pointe nor ventricular tachycardia were noted in Holter monitoring of 33 patients
      during the higher dose stage. CONCLUSION: cisapride dose-dependently prolongs the
      QT interval. Further study is needed to examine the arrhythmogenicity of
      cisapride in higher doses and for longer durations.

PMID- 11578712
TI  - Vascular endothelial growth factor expression in patients suffering from
      thrombangitis obliterans.

PMID- 11578713
TI  - Feasibility, safety, cost-effectiveness and 1 year follow-up of coronary stenting
      without predilation: a matched comparison with the standard approach.
AB  - BACKGROUND: We evaluated the feasibility, safety, procedural cost-effectiveness,
      radiation dose and time and 1-year target vessel revascularization rate of direct
      unprotected mounted stenting without previous balloon dilatation (DS) in native
      coronary artery lesions. METHODS: DS was attempted in 119 patients; 39 had a
      recent myocardial infarction, 62 had unstable angina, and 18 had stable angina.
      The clinical follow-up was obtained at 14+/-5 months (range 6 to 24 months).
      These results were compared with those for a consecutive group of 160 patients
      matched for type and length of lesions and who had a stent only if the post
      balloon residual stenosis was >30%. RESULTS: The feasibility of DS was 112/119
      (94%). The number of inflations, the length of the stent/length of the lesion
      ratio, the time and the dose of radiation were dramatically lower in the DS group
      (P<0.001). DS conferred a slight reduction in procedure-related cost [$820+/-157
      for DS vs. 894+/-427 for standard dilatation (SD) per patient]. The 1-year target
      vessel revascularization rate was similar in both groups [nine (8%) for DS vs. 17
      (11%) patients for SD, ns]. CONCLUSIONS: DS is feasible and safe in selected
      coronary lesions. This method provides a low rate of repeat revascularization and
      reduces the time and the dose of radiation compared with the standard approach.

PMID- 11578714
TI  - Short- and long-term prognostic value of cardiac troponin I and dobutamine
      echocardiography in patients with stabilized acute coronary syndromes.
AB  - BACKGROUND: This study investigated the short- and long-term prognostic values of
      cardiac troponin I (cTnI) and dobutamine echocardiography (DE) in patients with
      acute coronary syndrome (ACS) who stabilized after medical treatment. METHODS AND
      RESULTS: 171 consecutive patients of ACS accepted blood sampling for cTnI at the
      emergency department and DE at 4.9+/-0.6 days after admission. The prognostic
      values of cTnI, DE, and combined cTnI and DE were separately investigated at
      follow up periods of 30 days, 1 year and 3 years for hard events (cardiac death
      and non-fatal myocardial infarction) and all spontaneous events. CTnI was
      elevated in 55 (32%) patients and DE was positive in 114 (67%) patients. Elevated
      cTnI with positive DE were found in 44 (26%) patients. Within 30 days, the
      combination of elevated cTnI and positive DE provided more accurate prognostic
      information than each test result alone, and was the only independent predictor
      for both hard (p=0.014) and all events (p=0.012). After 1 year, cTnI alone had no
      prognostic value. The combination of an elevated cTnI level and a positive DE
      only had a prognostic value for all events (p=0.015). However, DE was an
      independent predictor for both hard (p=0.006) and all events (p=0.002). Neither
      cTnI alone nor cTnI combined with DE had a significant 3-year prognostic value.
      However, DE maintained its prognostic value and was still an independent
      predictor after 3 years for both hard (p=0.024) and all events (p=0.004).
      CONCLUSIONS: For patients with stabilized ACS, the diagnostic finding of elevated
      cTnI combined with a positive DE has a better short-term prognostic value than
      each test alone. However, DE alone has a better long-term prognostic value.

PMID- 11578715
TI  - Prior aspirin use in unstable angina predisposes to higher risk: the aspirin
      paradox.
AB  - BACKGROUND: Aspirin is the most widely prescribed agent used in prevention of
      coronary thrombosis. Thus, many patients presenting with acute coronary syndromes
      have a history of aspirin usage. METHODS: To assess response to medical therapy
      in patients taking aspirin prior to admission with an acute coronary syndrome, we
      reviewed outcomes data from the Efficacy and Safety of Subcutaneous Enoxaparin in
      Non-Q-wave Coronary Events (ESSENCE) and Platelet Receptor Inhibition in Ischemic
      Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM
      PLUS) studies. RESULTS: Patients with acute coronary syndromes who had taken
      aspirin prior to enrollment were less likely to have non-Q-wave myocardial
      infarction on admission (ESSENCE: 16.0% vs. 29.2%, p<0.001; PRISM-PLUS: 34.2% vs.
      57.7%, p<0.001). However, prior aspirin users were more likely to be failed by
      standard medical therapy with unfractionated heparin than non-prior aspirin users
      (ESSENCE: 21.5% vs. 16.5%, p=0.017; PRISM-PLUS: 23.5% vs. 12.1%, p<0.001). Prior
      aspirin users received greater benefit from both enoxaparin (21.5% vs. 16.8%,
      p=0.009) and tirofiban with unfractionated heparin (23.5% vs. 16.0%, p=0.007)
      than from unfractionated heparin alone. Non-prior aspirin users presented with
      higher rates of non-Q-wave myocardial infarction. CONCLUSIONS: Prior aspirin
      users admitted with acute coronary syndromes may have a more benign presentation,
      but are more likely to be failed by medical therapy with unfractionated heparin
      and should be considered as a high-risk group. Enoxaparin or the combination of
      tirofiban and unfractionated heparin are both more effective than unfractionated
      heparin in this group.

PMID- 11578716
TI  - Lack of association between polymorphisms of the coagulation factor VII and
      myocardial infarction in middle-aged Spanish men.
AB  - In order to determine the role of two polymorphisms in the factor VII gene (R353Q
      and intron 7 hypervariable region) in the susceptibility to develop early
      myocardial infarction, a total of 175 patients with acute myocardial infarction
      aged 50 years or less (mean age 41+/-7 years) and 200 controls (average age 42+/
      6) without cardiovascular disease were genotyped for these polymorphisms. Gene
      and genotype frequencies did not differ between patients and controls. Although
      the 353-QQ genotype was at a higher frequency among controls (4%) compared to
      patients (1%), the difference did not reach statistical significance. Carriers of
      the H7-allele (intron 7 polymorphism) were at a slightly higher frequency among
      patients (51 vs. 43%; P=0.19; OR=1.36; 95% CI=1.09-1.70). Our data suggest a lack
      of association between both polymorphisms in the factor VII gene and early
      myocardial infarction in our population.

PMID- 11578717
TI  - The epidemiological features of heart failure in developing countries: a review
      of the literature.
AB  - Cardiovascular diseases are increasingly recognised as an important cause of
      morbidity and mortality in developing countries. This is due to the ageing of the
      population and better control of communicable disease and malnutrition. We review
      the published data on the epidemiology of heart failure in such countries.
      Rheumatic heart disease remains a major cause of heart failure in Africa and
      Asia, especially in the young. Hypertension is an important cause of heart
      failure especially in the African and African-American population. Chagas'
      disease is still a cause of heart failure in South America. However, as countries
      go through epidemiological transition and undergo socio-economic development, the
      epidemiology of heart failure becomes increasingly similar to that of Western
      Europe and North America with coronary artery disease being the single most
      common cause of heart failure. Preventive and public health strategies need to be
      specific to the local epidemiological characteristics.

PMID- 11578718
TI  - Q-T and JT dispersion in the elderly with urban hypothermia.
AB  - Twenty elderly patients (12 females and 8 males, aged 65-88 years) were treated
      because of hypothermia: 11 suffered from moderate (35-32 degrees C) and nine from
      severe hypothermia (<32 degrees C). The control group consisted of 20 age and sex
      matched healthy elderly persons. Twelve-channel electrocardiograms were recorded
      on admission and during hospitalization. In patients with moderate hypothermia
      Osborn wave was present in eight of 11, and minimal Osborn wave in three of 11;
      in severe hypothermia Osborn wave was seen in seven of nine, and minimal in two
      of nine. The corrected Q-T interval (Q-Tc) was analyzed according to the formula
      of Bazett: measured Q-T(s)/ radical R-R(s). The JT and the corrected JT interval
      (JTc) were measured according to the formula: JT=Q-T-QRS. The Q-T interval index
      (Q-TI) was measured according to the formula: (Q-TI:656)x(HR+100); and the JT
      interval index JTI: (JT:518)x(HR+100). The dispersion of the Q-Tc (JTc) was
      defined as the difference between maximum and minimum measured Q-Tc interval
      (JTc). The Q-Tc interval in the group with hypothermia was 651.41+/-130.06 ms,
      while in the control group it was 398.14+/-76.21 ms (P<0.001). The Q-Tc
      dispersion in the group with hypothermia was 91.39+/-51.98, and in the control
      group 33.21+/-10.25 ms (P<0.001). The Q-TcI in the group with hypothermia was
      89.91+/-21.44, and in the control group 39.56+/-9.41 ms ((P<0.001). The JTc in
      the group with hypothermia was 542.66+/-132.74, in the control group: 328.06+/
      76.92 (P<0.001). The JTc dispersion in the group with hypothermia was 79.35+/
      46.22, and in the control group 28.53+/-7.99 (P<0.0001). The JTcI in the group
      with hypothermia was 93.06+/-17.38, in the control group it was 40.23+/-7.59
      (P<0.001). The mean values of the Q-TcI were greater than Q-TI, and the mean
      values of the JTcI were greater than JTI, but the difference was not significant
      (P>0.10). The mean values of the JTcI were greater than Q-TcI, but the difference
      was not significant as well (P>0.05). There was no correlation between rectal
      temperature and dispersion of Q-T, Q-Tc, JT, JTc, and Osborn wave. The maximum
      Osborn wave and the maximum Q-T interval were registered in anteroseptal leads
      (V(2)-V(3)). The dispersion of the Q-Tc and of the JTc lasted more than Osborn
      wave. There was no correlation between rectal temperature and PR interval, RR
      interval and QRS duration. The prolonged dispersion of the Q-Tc (and JTc) last 24
      48 h longer than Osborn wave.

PMID- 11578719
TI  - Prognostic implications of evaluation of contractile reserve in akinetic and
      hypokinetic segments during low dose dobutamine echocardiography in patients with
      acute myocardial infarction.
AB  - BACKGROUND: Previous studies have reported the prognostic value of myocardial
      viability (MV) detected using low-dose dobutamine echocardiography (DbE).
      However, viability was frequently evaluated as improvement in regional wall
      motion score index, which includes increased function in hypokinetic segments, in
      which viable myocardium is necessarily present. It is not known whether an
      evaluation focusing on akinetic segments, in which the possible presence of
      viable myocardium is unknown, might have more prognostic value. The aim of this
      study was to compare the prognostic value of the improvement of myocardial
      function during dobutamine infusion in akinetic and hypokinetic regions in
      patients with acute myocardial infarction (AMI). METHODS: 191 patients with
      uncomplicated AMI and at least one akinetic segment were retrospectively selected
      from those consecutively examined at our echo-laboratory to evaluate MV using
      DbE. Myocardial viability was evaluated both as an increment in RWMSI (Delta
      RWMSI), which takes into consideration improvement in both akinetic and
      hypokinetic regions, and as an improvement of function in akinetic (Delta
      akinetic) and hypokinetic (Delta hypokinetic), segments considered separately.
      Follow-up evaluation was performed at 30+/-13 months. RESULTS: On the basis of
      the Delta RWMSI, 94/191 patients were judged to have myocardial viability,
      whereas considering myocardial viability in akinetic segments only, 72/191
      patients showed viability. At follow-up 18 patients had died (six viable
      considering Delta RWMSI; three viable considering Delta akinetic). The presence
      of a previous AMI, the site of AMI, RWMSI and the number of akinetic segments,
      and Delta RWMSI and Delta akinetic were related to mortality at univariate Cox
      analysis. At multivariate stepwise Cox regression analysis Delta akinetic, but
      not Delta hypokinetic proved to be significantly related to mortality. The Kaplan
      Meier survival curves were no different in patients with or without viable
      myocardium evaluated as Delta RWMSI, while they were significantly different
      considering patients with or without viability in akinetic segments (P=0.04).
      CONCLUSION: In conclusion our study confirms the prognostic importance of the
      evaluation of myocardial viability in infarcted patients. However, it points out
      that it is the presence of viability in akinetic segments that affects long-term
      survival in these patients. This supports the hypothesis that other mechanisms,
      above and beyond the effect on regional wall motion, are involved in the
      beneficial effects of myocardial viability.

PMID- 11578720
TI  - Platelet hyperaggregability persists even after the improvement of increased
      blood coagulation and impaired fibrinolysis with the stabilization of symptoms in
      patients with unstable angina.
AB  - BACKGROUND: Platelet aggregation, blood coagulation, and fibrinolysis play a
      pivotal role in the pathogenesis of unstable angina. METHODS: Platelet
      aggregability was examined on admission and after 2 weeks of treatment in 22
      patients with unstable angina, in particular with regard to small-sized platelet
      aggregates, plasma tissue factor (TF) antigen levels as a marker of blood
      coagulation, and plasma plasminogen activator inhibitor (PAI) activity levels as
      an indicator of fibrinolysis. We also examined the same parameters in 19 patients
      with stable exertional angina and 17 patients with chest pain syndrome. RESULTS:
      The number of small-sized platelet aggregates increased more significantly in the
      unstable angina group than in the stable exertional angina and chest pain
      syndrome groups. In the unstable angina group, the number of small-sized platelet
      aggregates decreased significantly after 2 weeks of treatment, but was still
      higher than that in the stable exertional angina and chest pain syndrome groups.
      Plasma TF antigen and PAI activity were higher in the unstable angina group than
      in the stable exertional angina and chest pain syndrome groups. TF and PAI
      activity decreased to normal ranges after 2 weeks of treatment in the unstable
      angina group. There were significant positive correlations among the three
      parameters on admission. CONCLUSIONS: It was demonstrated that small-sized
      platelet aggregates, plasma TF antigen and PAI activity levels increased
      concomitantly in the unstable angina group. While the blood coagulation and
      fibrinolytic parameters decreased after stabilization of the clinical symptoms,
      platelet hyperaggregability still persisted. These results suggest that
      continuous antiplatelet therapy is essential for the treatment of unstable
      angina.

PMID- 11578721
TI  - Urinary excretion of biopyrrins, oxidative metabolites of bilirubin, increases
      after spasm provocation tests in patients with coronary spastic angina.
AB  - BACKGROUND: Bilirubin apparently functions as an antioxidant in vivo by reacting
      with reactive oxygen species, and, as a result, becomes oxidized. The urinary
      excretion of oxidative metabolites of bilirubin, biopyrrins, could be a
      biological marker for in vivo production of reactive oxygen species. The purpose
      of this study was to examine the extent of oxidative stress in patients with
      possible ischemic heart diseases (n=44) by measuring urinary biopyrrins by enzyme
      linked immunosorbent assay before and after the spasm provocation test (SPT).
      METHODS: Spot urine samples were collected five times; 1 day before, in the
      morning just before, immediately after, 6 h after, and 1 day after the SPT.
      Nineteen patients were positive to SPT judged from the specific changes in
      electrocardiogram for myocardial ischemia following intracoronary injections of
      ergonovine. RESULTS: The baseline data such as age, sex, number of risk factors
      and concentrations of serum bilirubin, and the measured hemodynamic parameters of
      heart rate, blood pressure, left ventricular end-diastolic pressure and left
      ventricular ejection fraction were not different between the positive and
      negative groups. The baseline concentrations of biopyrrins during the control
      period were not significantly different between the two groups. However, they
      increased significantly after the SPT, thereby the magnitude of increases
      immediately after and 6 h after the SPT were significantly (P<0.001 and P<0.01,
      respectively) greater in the positive group than in the negative. CONCLUSION: The
      present findings strongly suggest that coronary arterial occlusion augments
      production of biopyrrins, which indicates exposure to oxidative stress in
      patients with ischemic heart diseases.

PMID- 11578722
TI  - Pre- or postoperative radiotherapy in rectal cancer--more to learn?

PMID- 11578723
TI  - Postoperative pelvic radiotherapy with or without elective irradiation of para
      aortic nodes and liver in rectal cancer patients. A controlled clinical trial of
      the EORTC Radiotherapy Group.
AB  - OBJECTIVE: The purpose of this randomized multicenter study was to assess the
      impact on disease free and overall survival of low dose irradiation to para
      aortic nodes and liver in patients with a locally advanced resected rectal cancer
      receiving a 50 Gy postoperative pelvic radiotherapy. PATIENTS AND METHODS: Main
      inclusion criteria were: a curative resection for a histologically proved
      carcinoma of the rectum, Gunderson-Sosin stages B2-B3, C1-C3, age <70 years. The
      patients were randomized between pelvic irradiation (Lim-XRT): 50 Gy in 25
      fractions over 5 weeks and extended irradiation (Ext-XRT): same scheme/doses in
      the pelvis and extended fields on para-aortic nodes and liver, delivering 25 Gy
      in 19 fractions over 25 days. From 1983 to 1992, 484 patients were enrolled by 18
      EORTC institutions and 29 patients were ineligible. The end-points were local and
      distant relapses, toxicity and survival. RESULTS: Compliance to treatment: 87.2%
      in Lim-XRT arm and 71.8% in Ext-XRT arm. Moderate acute hematological and hepatic
      toxicities were significantly increased in Ext-XRT arm. Among 325 patients at
      risk, 44 suffered a severe intestinal complication requiring surgery in 29. The 5
      and 10-year estimates of disease free survival were respectively 42 and 31% in
      Lim-XRT arm and 47 and 31% in Ext-XRT arm (ns). The corresponding figures for
      overall survival were respectively 45 and 40% in Lim-XRT arm and 48 and 37% in
      Ext-arm (ns). The 10 years estimate of intra-pelvic failures was approximately
      30% in both arms. Patients in Ext-arm appeared to have a slight shorter interval
      free of liver metastases (P=0.047). CONCLUSION: Low dose irradiation to the para
      aortic nodes and liver did not improve survival for patients with resected
      adenocarcinoma of the rectum.

PMID- 11578724
TI  - Radiation therapy for epidermoid carcinoma of the anal canal, clinical and
      treatment factors associated with outcome.
AB  - BACKGROUND AND PURPOSE: In recent years, treatment with combined chemotherapy and
      radiation has become the standard of care for epidermoid carcinoma of the anus.
      However, optimal radiotherapy techniques and doses are not well established.
      MATERIALS AND METHODS: During the period 1975-1997, 106 patients with epidermoid
      carcinoma of the anal canal underwent radiation therapy. Treatment policies
      evolved from radiation therapy alone or with surgery, to combined chemotherapy
      and radiation followed by surgery, to combined chemotherapy and radiation.
      RESULTS: Overall 74% of patients were NED (no evidence of disease) at last follow
      up. The most important clinical correlate with ultimate freedom from disease
      (includes the contribution of salvage surgery) was extent of disease. The 5-year
      ultimate freedom from disease was 87+/-5% for T1/T2N0, 78+/-10% for T3N0 (15%
      salvaged by surgery), and 43+/-10% for either T4N0 or any N+ lesions (P<0.001,
      Tarone-Ware). There was no difference between planned vs. expectant surgery (5
      year ultimate NED: 67+/-11% planned surgery vs. 73+/-5% expectant surgery). The
      most important correlate with late toxicity was a history of major pelvic surgery
      (surgical vs. non-surgical group: P=0.013, Fisher's exact test, two-tailed
      summation). Thirty-three additional malignancies have been seen in 26 patients.
      The most common additional malignancies were gynecologic (nine cases), head and
      neck (six cases), and lung cancer (five cases). CONCLUSIONS: For T1/T2N0 disease,
      moderate doses of radiation combined with chemotherapy provided adequate
      treatment. T4N0 and N+ lesions are the most appropriate candidates for
      investigational protocols evaluating dose intensification. T3N0 tumors may also
      be appropriate for investigation; however, dose intensification may ultimately
      prove counterproductive if the cure rate is not improved and salvage surgery is
      rendered more difficult. The volume of irradiated small bowel should be minimized
      for patients who have a past history of major pelvic surgery or who (because of
      locally advanced tumors) may need salvage surgery in the future. Because of the
      occurrence of additional malignancy, patients with anal cancer should receive
      general oncologic screening in long-term follow-up.

PMID- 11578725
TI  - Accommodation of couch constraints for coplanar intensity modulated radiation
      therapy.
AB  - PURPOSE: Three treatment couches, henceforth referred to as the standard, the
      variable standard and the C-arm couch, each based on a different supporting frame
      system, were investigated for their suitability for the delivery of a high number
      of coplanar beams (> or =5) as may be required for intensity-modulated radiation
      therapy treatments. MATERIALS AND METHODS: A number of equispaced beam
      arrangements (five to nine) were examined in combination with two circular target
      sizes (Phi6 and Phi10 cm) at different locations within an elliptical body on the
      investigated couches, resulting in 70 different plans per couch. A rule based
      advisory system determined possible intersections of the beam paths with the
      supporting frames of the respective treatment couch and suggested a suitable
      constellation for the supporting frames. In cases of intersection, a beam-couch
      collision was eliminated by minimal rotation of the beams from the initial
      equispaced beam arrangement. To investigate the effect of a rotation of the
      posterior-oblique beams for five, seven and nine initially equispaced beams by an
      angle of 10 degrees, a prostate plan was generated and compared with equispaced
      beam arrangement. RESULTS: Initial beam paths intersected with the standard couch
      in 63% of the plans, necessitating a rotation of one or two beams. It was
      necessary to modify the beam angles in 34% of the cases on the variable standard
      couch to avoid an intersection of the beams with the couch. All the plans would
      have been delivered satisfactorily on the C-arm couch without a rotation of
      beams. Simulation studies showed that the dose distribution for a prostate
      treatment could be affected significantly, but not detrimentally, by the rotation
      of the two posterior-oblique beam orientations by an angle of 10 degrees.

PMID- 11578726
TI  - Optically guided intensity modulated radiotherapy.
AB  - BACKGROUND AND PURPOSE: Previously, we reported on development of an optically
      guided system for 3D conformal intracranial radiotherapy using multiple
      noncoplanar fixed fields. In this paper we report on the extension of our system
      for stereotactic fractionated radiotherapy to include intensity modulated static
      ports. METHODS AND MATERIALS: A 3D treatment plan with maximum beam separation is
      developed in the stereotactic space established by an optically guided system.
      Gantry angles are chosen such that each beam has a unique entrance and exit
      pathway, avoids the critical structures, and has a minimal beam's eye view
      projection. Once, a satisfactory treatment plan is found using this geometric
      approach an inverse treatment plan is developed using the beam portals
      established previously. The purpose of adding inverse planing is two fold, on the
      one hand it allows further reduction of margins around the PTV, while on the
      other hand it affords the possibility of conformal avoidance of critical
      structures that are close to or abut the PTV. RESULTS: The use of the optically
      guided system in conjunction with intensity modulated noncoplanar radiotherapy
      treatment planning using fixed fields allows the generation of highly conformal
      treatment plans that exhibit smaller 90, 70, and 50% of prescription dose isodose
      volumes, improved PITV ratios, comparable or improved EUD, smaller NTD(mean) for
      the critical structures, and an inhomogeneity index that is within generally
      accepted limits. CONCLUSION: Because optically guided technology improves the
      accuracy of patient localization relative to the linac isocenter and allows real
      time monitoring of patient position, the planning target volume needs to be
      corrected only for the limitations of image resolution. Intensity modulated
      static beam radiotherapy planning then provides the user the ability to further
      reduce margins on the PTV and to conform very closely to this smaller target
      volume, and enhances the normal tissue sparing, and high degree of conformality
      possible with 3D conformal radiotherapy. In addition, since optically guided
      technology affords improved patient localization and online monitoring of patient
      position during treatment delivery it allows for safe and efficient delivery of
      intensity modulated radiotherapy.

PMID- 11578727
TI  - Development of a criterion for repositioning a relocatable stereotactic frame
      using depth helmet measurements.
AB  - Based on 95% confidence intervals in the normal distribution, a criterion was
      developed for a relocatable stereotactic frame depth helmet measurement. The
      method for obtaining such a criterion is described. The criterion states that, if
      more than two points deviate more than 1.5 mm the frame should be repositioned.

PMID- 11578728
TI  - A linac-based stereotactic irradiation technique of uveal melanoma.
AB  - PURPOSE: To describe a stereotactic irradiation technique for uveal melanomas
      performed at a linac, based on a non-invasive eye fixation and eye monitoring
      system. METHODS: For eye immobilization a light source system is integrated in a
      standard stereotactic mask system in front of the healthy eye: During treatment
      preparation (computed tomography/magnetic resonance imaging) as well as for
      treatment delivery, patients are instructed to gaze at the fixation light source.
      A mini-video camera monitors the pupil center position of the diseased eye. For
      treatment planning and beam delivery standard stereotactic radiotherapy equipment
      is used. If the pupil center deviation from a predefined 'zero-position' exceeds
      1 mm (for more than 2 s), treatment delivery is interrupted. Between 1996 and
      1999 60 patients with uveal melanomas, where (i) tumor height exceeded 7 mm, or
      (ii) tumor height was more than 3 mm, and the central tumor distance to the optic
      disc and/or the macula was less than 3 mm, have been treated. A total dose of 60
      or 70 Gy has been given in 5 fractions within 10 days. RESULTS: The repositioning
      accuracy in the mask system is 0.47+/-0.36 mm in rostral-occipital direction,
      0.75+/-0.52 mm laterally, and 1.12+/-0.96 mm in vertical direction. An eye
      movement analysis performed for 23 patients shows a pupil center deviation from
      the 'zero' position<1 mm in 91% of all cases investigated. In a theoretical
      analysis, pupil center deviations are correlated with GTV 'movements'. For a
      pupil center deviation of 1 mm (rotation of the globe of 5 degrees ) the GTV is
      still encompassed by the 80% isodose in 94%. CONCLUSION: For treatments of uveal
      melanomas, linac-based stereotactic radiotherapy combined with a non-invasive eye
      immobilization and monitoring system represents a feasible, accurate and
      reproducible method. Besides considerable technical requirements, the complexity
      of the treatment technique demands an interdisciplinary team continuously
      dedicated to this task.

PMID- 11578729
TI  - Gliosarcoma: a clinical study.
AB  - BACKGROUND AND PURPOSE: Gliosarcomas are rare biphasic neoplasms of the central
      nervous system composed of a glioblastoma multiforme (GBM) admixed with a
      sarcomatous component. There are conflicting reports regarding their clinical
      aggressiveness. Four hundred and twenty-two consecutive patients with GBM were
      treated at our hospital between 1980 and 1999, among them 12 gliosarcomas. The
      goal of this study was to examine clinical features, treatment, survival and
      patterns of failure of gliosarcoma patients and to compare them with the entire
      group of GBM patients. This comparison was refined by a matched pair analysis
      with a group of 12 GBM patients selected for age, Karnofsky performance status,
      resection status, fractionation scheme and total dose (control GBM group).
      MATERIALS AND METHODS: Seven gliosarcoma patients were male, five female, with a
      median age of 56 years (range 37-76 years). The median tumor size was 4.5 cm
      (range 3-8 cm). The locations, all supratentorial, included temporal in six,
      parietal in five, frontal in four and occipital in one patient. All patients
      underwent tumor resection followed by postoperative radiation therapy. RESULTS:
      Median survival was 11.5 months for the gliosarcoma group, 8.1 months for the
      entire GBM group (log rank test, P=0.16) and 11.0 months for the control GBM
      group (log rank test, P=0.36). All gliosarcoma patients had local tumor
      recurrences and died due to neurologic causes within 19.3 months after radiation
      therapy. CONCLUSIONS: With regard to clinical features, survival and patterns of
      failure, gliosarcomas and GBM cannot be distinguished clinically. Therefore, the
      same principles should be applied for the treatment of these tumors.

PMID- 11578730
TI  - Efficacy of external fractionated radiation therapy in the treatment of
      meningiomas: a 20-year experience.
AB  - BACKGROUND: This is a retrospective analysis of a series of meningiomas treated
      by radiotherapy. MATERIALS AND METHODS: From 1978 to 1997, 45 patients with
      intracranial meningiomas were referred for external fractionated radiotherapy at
      Centre Alexis Vautrin. All patients were given 50-70Gy to the tumor bed (median:
      56Gy), 1.8-2Gy per fraction. RESULTS: Evaluation was performed in June 1999 using
      the Kaplan-Meyer actuarial method with a median follow-up of 30 months (range: 1
      166), relapse-free survivals (RFSs) were 75% at 5 years and 67% at 8 years;
      overall survival (OS) was 74% at 5 and 8 years. For the 26 benign histologically
      documented lesions, RFSs were 95% at 5 years and 81% at 8 years; OS was 85% at 5
      and 8 years. One major radiation-induced complication occurred in this series
      (decline of cognitive function). According to the indication of radiotherapy, we
      divided the series into four groups: postoperative irradiation after a first
      subtotal resection (11 patients), 5-year RFS was 90%; after first recurrence (+/
      salvage surgery, 14 patients), 73%; after further recurrence (+/-salvage surgery,
      11 patients), 67%; as exclusive treatment (nine patients), 80%. Atypical and
      malignant lesions (n=7) all relapsed before 24 months of follow-up, all patients
      but one died before 42 months. Age at the time of irradiation (> or =60 vs. <60
      years) and radiotherapy dose (> or =60 vs. <60Gy) did not influence local control
      or OS. Atypical and malignant lesions (WHO grades II and III) meningiomas had a
      worse outcome than benign lesions (WHO grade I, P<0.01). CONCLUSIONS: These
      results compare favorably with previously published data. External fractionated
      radiotherapy is well tolerated and effective. There is still a debate about the
      place of radiotherapy in the treatment of meningiomas: after subtotal resection,
      should radiotherapy be given postoperatively or at the time of progression?
      Should radiotherapy replace surgery when the risk of postoperative sequellae is
      high? Prospective randomized trials would be required to address these issues.

PMID- 11578731
TI  - Radiotherapy for brain metastases: defining palliative response.
AB  - BACKGROUND AND PURPOSE: Most patients with brain metastases are treated with
      palliative whole brain radiotherapy (WBRT). There is no established definition of
      palliative response. The aim of this study was to develop and test clinically
      useful criteria for response following palliative WBRT. MATERIALS AND METHODS: A
      prospective study was conducted of patients with symptomatic brain metastases
      treated with WBRT (20 Gy/5 fractions) and standardised steroid tapering.
      Assessments included observer rating of neurological symptoms, patient-completed
      symptom checklist and performance status (PS). Response criteria were
      operationally defined based on a combination of neurological symptoms, PS and
      steroid dose. RESULTS: Seventy-five patients were accrued. At 1 month, presenting
      neurological symptoms were improved in 14 patients, stable in 17, and worse in
      21; 23 patients were not assessed, mainly due to death or frailty. Using response
      criteria defined a priori, 15% (95% CI 7-23%) of patients were classified as
      having a response to RT, 25% no response, and 29% progression; 27% were deceased
      at or soon after 1 month. A revised set of criteria was tested, with less
      emphasis on complete tapering of steroids: they increased the proportion of
      patients responding to 39% (95% CI 27-50%) but didn't change the large proportion
      who did not benefit (44%). CONCLUSIONS: Clinical response to RT of patients with
      brain metastases is multifactorial, comprising symptoms, PS and other factors.
      Assessment of degree of palliation depend on the exact definition used. More
      research is needed in this important area, to help validate criteria for
      assessing palliation after WBRT.

PMID- 11578732
TI  - Prospective patient-based assessment of effectiveness of palliative radiotherapy
      for bone metastases.
AB  - PURPOSE: The primary objective of this report is to prospectively evaluate pain
      control provided by palliative radiotherapy for all irradiated patients with bone
      metastases by using their own assessments. MATERIALS AND METHODS: A prospective
      database was set up for all patients referred for palliative radiotherapy for
      bone metastases. Patients were asked to rate their pain intensity using an 11
      categorical point scale (0=lack of pain, 10=worst pain imaginable). Analgesic
      consumption during the preceding 24 h was recorded and converted into equivalent
      total daily dose of oral morphine. For those who received radiotherapy, follow-up
      was conducted via telephone interviews at week 1, 2, 4, 8 and 12 post treatment
      using the same pain scale and analgesic diary. Radiotherapy outcome was initially
      assessed by pain score alone. Complete response (CR) was defined as a pain score
      of 0. Partial response (PR) was defined as a reduction of score > or =2 or a> or
      =50% reduction of the pre-treatment pain score. We further analyzed outcomes
      using integrated pain and analgesic scores. Response was defined as either a
      reduction of pain score > or =2 with at least no increase in analgesics or at
      least stable pain score with a > or =50% reduction in analgesic intake. RESULTS:
      One hundred and five patients were treated with palliative radiotherapy. When
      response evaluation was by pain score alone, the PR rates at 2, 4, 8 and 12 weeks
      were 44, 42, 30 and 38%, respectively; while the CR rates were 24, 32, 31 and
      29%, respectively. The overall response rate at 12 weeks was 67%. When assessed
      by the integrated pain and analgesic scores, the response rates were 50, 46, 43
      and 43%, respectively. CONCLUSION: The response rate in our patient population is
      comparable with those reported in clinical trials. This is important when
      counselling our patients on the expected effectiveness of radiotherapy outside of
      clinical trials. Our observations confirm the generalizability of the trials
      conducted to date. While randomized trials still remain the gold standard of
      research, observational studies can serve as useful adjuncts to randomized trials
      to confirm the efficacy and guide the design of new controlled trials.

PMID- 11578733
TI  - Comparison of dose-volume histograms and dose-wall histograms of the rectum of
      patients treated with intracavitary brachytherapy.
AB  - The correlation between dose values from dose-volume histograms (DVHs) and dose
      values from dose-wall histograms (DWHs) of the rectum tissue of patient with
      uterine cervix cancer was determined. The minimum dose in 2 cm3 in the high-dose
      region of the DVH is a good estimate of the dose in the rectum wall.

PMID- 11578734
TI  - Proposal of a new grading system for evaluation of tongue hemiatrophy as a late
      effect of brachytherapy for oral tongue cancer.
AB  - PURPOSE: To evaluate tongue hemiatrophy as a late effect of brachytherapy, a new
      grading system was designed and applied to patients who had received low dose
      rate (LDR) or high dose rate (HDR) brachytherapy for early tongue cancer. METHODS
      AND MATERIALS: Between December 1998 and April 1999, 49 patients who had received
      brachytherapy for early tongue cancer (T1/T2=22:27) at Osaka University Hospital
      were investigated. All patients had undergone either LDR or HDR brachytherapy
      with Ir-192 (LDR/HDR=30:19) between 1980 and 1998. Atrophic changes in their
      tongue were classified into four categories (G0-G3): G3, not able to protrude the
      tongue beyond incisors; G2, hemiatrophy is seen on the irradiated side in the
      resting position of the tongue; G1, deviation of the tip of the tongue to the
      irradiated side is seen when protruded; and G0, none of these signs. The
      relationship between tongue hemiatrophy and tumor factors, treatment factors, and
      patients' functional impairment was then investigated. The median time from
      treatment to assessment was 75 months (range 8-219 months). Volume index was
      defined as the number of needles that were implanted vertically into the tongue.
      RESULTS: Fourteen patients were classified as G0, 29 as G1, five as G2, and one
      as G3. None of the G0 patients showed any speech or swallowing dysfunction, pain
      or contracted feeling, or general dissatisfaction with post-treatment tongue
      status. There was a tendency for such problems to increase with the tongue
      hemiatrophy grade. The frequency of T2 and non-superficial type tumors also
      tended to increase with the tongue hemiatrophy grade. The volume index of the G2
      3 hemiatrophy group was significantly larger than that of the G0-1 group
      (P=0.041). CONCLUSION: This new grading system makes evaluation of atrophic
      changes in the tongue after brachytherapy easy and effective.

PMID- 11578735
TI  - Dosimetric consequences of tumor mobility in radiotherapy of stage I non-small
      cell lung cancer--an analysis of data generated using 'slow' CT scans.
AB  - BACKGROUND: The target coverage for radiotherapy of early-stage lung cancer was
      evaluated using two different CT techniques. MATERIALS AND METHODS: A
      conventional planning CT scan and two limited scans of the tumor region were
      performed in seven patients with peripheral tumors. Three 'slow' scans (slice
      thickness 4mm, index 3mm, revolution time 4s/slice) were then performed, followed
      by three-dimensional image registration. Planning target volumes (PTV) were
      generated using these GTV-PTV margins: (a) 1cm (PTV1.0); (b) 1.5 cm (PTV1.5); and
      (c) 0.9, 1.0, and 0.9 cm ('PTV(clinical)') when set-up errors are avoided.
      RESULTS: PTVs derived from three 'slow' scans missed 1.9% of the volume derived
      from three planning scans for an immobile tumor and 9.3% in the case of a mobile
      tumor. For an immobile tumor, PTV1.5 achieved comparable coverage to that
      achieved using PTVclinical, which was generated from three 'slow' scans and a
      planning scan. For a mobile tumor, PTV(1.5) covered only 89% of the volume
      captured by PTVclinical. PTV1.0 resulted in inadequate target coverage in all the
      patients. Reductions in potential lung toxicity (V20) were achievable in six
      patients despite the larger GTVclinical when treatment set-up errors were
      minimized. CONCLUSIONS: PTVs derived using 'slow' CT scans consistently produce
      superior target coverage than that using conventional scans. This may account for
      the poor local control observed in stage I lung cancer.

PMID- 11578736
TI  - Non-aqueous encapsulation of excipient-stabilized spray-freeze dried BSA into
      poly(lactide-co-glycolide) microspheres results in release of native protein.
AB  - Encapsulation of the model protein bovine serum albumin (BSA) into poly(D,L
      lactide-co-glycolide) (PLG) microspheres was performed by a non-aqueous oil-in
      oil (o/o) methodology. Powder formulations of BSA obtained by spray-freeze drying
      were first suspended in methylene chloride containing PLG followed by
      coacervation by adding silicon oil and microsphere hardening in heptane. The
      secondary structure of BSA was determined at relevant steps of the encapsulation
      procedure by employing Fourier-transform infrared (FTIR) spectroscopy. This fast
      and non-invasive method demonstrated the potential to rapidly screen
      pharmaceutically relevant protein delivery systems for their suitability.
      Structural perturbations in BSA were reduced during the spray-freeze drying step
      by employing the excipient trehalose. The protein was then encapsulated into PLG
      microspheres under various conditions without inducing significant structural
      perturbations. BSA released from these microspheres had a similar monomer content
      as unencapsulated BSA and also the same secondary structure. Upon blending of a
      poloxamer (Pluronic F-68) with the polymer phase, in vitro release was
      characterized by a small initial release and a prolonged and continuous sustained
      phase. In conclusion, the developed o/o methodology coupled with FTIR
      spectroscopic monitoring of protein structure is a powerful approach for the
      development of sustained release microspheres.

PMID- 11578737
TI  - Poly(ethylene carbonate)s, part II: degradation mechanisms and parenteral
      delivery of bioactive agents.
AB  - The degradation and drug carrier properties of poly(ethylene carbonate) (PEC)
      were investigated in vitro and in rats and rabbits. PEC was found to be
      specifically degraded in vivo and in vitro by superoxide radical anions O2-*,
      which are, in vivo, mostly produced by inflammatory cells. No degradation of PEC
      was observed in the presence of hydrolases, serum or blood. PEC is biodegraded by
      surface erosion without significant change in the molecular weight of the
      residual polymer mass. The non-hydrolytic biodegradation by cells producing O2-*
      is unique among the polymers used as biodegradable drug carriers. The main
      degradation product of PEC in aqueous systems is ethylene glycol, formed
      presumably by hydrolysis of ethylene carbonate. The splitting off of a five
      membered ring structure from the polymer chain indicates a chain reaction
      mechanism for the biodegradation. PEC is a suitable drug carrier, particularly
      for labile drugs. Using human interleukin-3 and octreotide as model drugs,
      surface erosion of the PEC formulations was indicated by a 1:1 correlation
      between drug release and polymer mass loss.

PMID- 11578738
TI  - Alkyl-substituted silica gel as a carrier in the controlled release of
      dexmedetomidine.
AB  - The effect of alkyl substitution of the silica xerogel matrix on the release rate
      of dexmedetomidine was evaluated. Silica sol was processed by either casting or
      spray drying. When the reaction precursor tetraethylorthosilicate (TEOS) was
      partially substituted with tri- or dialkoxysilane, the release of dexmedetomidine
      and degradation of the matrix were decreased compared with 100% TEOS-based gel.
      Increasing the number or length of the organic groups attached to silicon,
      modified the silica gel structure and reduced the release rate of dexmedetomidine
      from monoliths. The release of dexmedetomidine from alkyl-substituted silica gel
      microparticles, however, showed a burst in drug release. Subcutaneously
      administered silica xerogel matrices (manufactured by casting, containing 25 mol%
      dimethyldiethoxysilane at two different doses of dexmedetomidine) were studied in
      dogs. Sustained delivery of dexmedetomidine was obtained for at least 48 h.

PMID- 11578739
TI  - Fabrication, characterization and in vitro release of paclitaxel (Taxol) loaded
      poly (lactic-co-glycolic acid) microspheres prepared by spray drying technique
      with lipid/cholesterol emulsifiers.
AB  - Spray dry technique was applied to produce paclitaxel loaded microspheres of
      biodegradable poly (lactic-co-glycolic acid) (PLGA) as an alternative delivery
      system. Various emulsifiers such as L-alpha-dipalmitoyl-phosphatidylcholine
      (DPPC), cholesterol, polyvinyl alcohol (PVA), gelatin were incorporated in order
      to achieve high encapsulating efficiency of paclitaxel in the microspheres and
      desired properties for a sustained release. Atomic force microscopy (AFM) and
      scanning electron microscopy (SEM) showed that the surface of the microspheres
      with high ratio of lipid was spherical and smooth. Those made with other
      emulsifiers had rougher surface with pores. Incorporation of lipid, cholesterol
      or gelatin can significantly increase the drug content in the microspheres. The
      differential scanning calorimetry (DSC) result indicated that the paclitaxel
      trapped in the microspheres existed in an amorphous or disordered-crystalline
      status in the polymer matrix. The zeta potential of the microspheres was negative
      in general and was strongly influenced by the type of the emulsifiers used in
      fabrication. The system formulated with cholesterol was most stable. The release
      profiles of various formulations with PVA, gelatin as well as low ratio of DPPC
      showed almost zero-order release kinetics in the first 3 weeks after an initial
      burst less than 5% in the first day. The release rate then gradually decreased.
      The microspheres fabricated with high ratio of DPPC exhibited large initial
      burst. When cholesterol was combined together with DPPC as an emulsifier, the
      release became faster.

PMID- 11578740
TI  - Controlled release and ocular absorption of tilisolol utilizing ophthalmic insert
      incorporated lipophilic prodrugs.
AB  - To control ocular drug delivery, the O-butyryl ester prodrug of tilisolol (BUTL)
      and the O-palmitoyl ester prodrug of tilisolol (PalTL) were incorporated into an
      ophthalmic insert. The released TL from BUTL inserts and PalTL inserts in pH 7.4
      phosphate-buffered saline until 5 h were approximately 25% and 3% of that from TL
      inserts, respectively. In addition, BUTL was also released from BUTL inserts.
      However, PalTL was not released from the PalTL insert. The release of drugs from
      TL inserts and BUTL inserts was little affected by the addition of bovine serum
      albumin (BSA) in pH 7.4 phosphate-buffered saline. In contrast, the release of
      drugs from PalTL inserts were enhanced by the addition of BSA. After application
      of TL, BUTL, and PalTL inserts to the rabbit eye, the aqueous humor concentration
      of TL was prolonged compared with TL instillation, and the plasma concentration
      of TL was much lower than that of TL instillation. The ratios of the area under
      the TL concentration-time curve (AUC) in the aqueous humor to AUC in the plasma
      (AUC(aqueous)/AUC(plasma)) after application of BUTL until 8 h were 3.1-fold and
      3.8-fold higher than those of the TL insert and PalTL insert, respectively.

PMID- 11578741
TI  - Stimuli-responsive properties of conjugates of N-isopropylacrylamide-co-acrylic
      acid oligomers with alanine, glycine and serine mono-, di- and tri-peptides.
AB  - A random oligomer of N-isopropylacrylamide (NIPAAm) and acrylic acid (AAc) with a
      AAc content of 3.1+/-0.19 mmol carboxylic acid groups per gram of the oligomer
      and with a number average molecular weight of 1400 was synthesised by a free
      radical polymerisation using AIBN in DMF. Then, mono-, di-, and tri-peptide
      conjugates of this oligomer were prepared by using carboxyl-ends-protected (with
      methyl ester hydrochloride) forms of alanine, glycine and serine, with a water
      soluble carbodiimide. 95, 93, and 31% of the carboxylic acids were conjugated
      (loaded) at the first step (mono-peptides) with glycine, alanine and serine,
      respectively. At the second step, percentage of the conjugation of carboxylic
      acid groups with glycine, alanine and serine were between 99 and 80, 68 and 100,
      and 21 and 58%, respectively, while the third amino acids were attached to only
      21-64% of the carboxylic acids available on the conjugate chains. A decrease was
      observed in the lower critical solution temperatures (LCSTs) of the amino acid
      conjugates at pH 4.0 compared with the unconjugated oligomer, which has LCST at
      37.7 degrees C at the same pH. LCSTs of di- and tri-peptide conjugates at pH 4.0
      were in the range of 38.4-43.3 degrees C, and 42.6-50.8 degrees C, respectively.
      At pH 7.4, LCSTs of the mono- and di-peptide conjugates were observed in the
      range of 41.6-43.9 degrees C, and 46.2-60.2 degrees C, respectively, while the co
      oligomer at pH 7.4 did not show a LCST up to 60 degrees C. Tri-peptide conjugates
      did not display LCST at pH 7.4, except the one with glycine-alanine-serine
      sequence.

PMID- 11578742
TI  - Protein release microparticles based on the blend of poly(D,L-lactic-co-glycolic
      acid) and oligo-ethylene glycol grafted poly(L-lactide).
AB  - Bovine serum albumin (BSA), a model protein drug, was encapsulated with a
      microparticle based on the blend of poly(D,L-lactic-co-glycolic acid) (PLGA) and
      poly(L-lactide)-g-oligo(ethylene glycol) (PLLA-g-oligoEG). Effects of PLLA-g
      oligoEG in the blend on degradation, characteristic properties, and release
      behavior of the microparticle were studied. Drug loading efficiency increased
      with increase in the graft frequency of oligoEG in the graft copolymer in the
      blend. The release of BSA was found to be more efficient for microparticles based
      on the blend than on the PLGA, which is due to the faster protein diffusion
      through the swollen phase of the hydrogel-like structure. The microparticles
      based on the blend showed a slower degradation and a lower pH shift compared to
      that of PLGA.

PMID- 11578743
TI  - Conjugation of anti-My9 antibody to stealth monensin liposomes and the effect of
      conjugated liposomes on the cytotoxicity of immunotoxin.
AB  - The carboxylic ionophore, monensin, was successfully entrapped in stealth
      liposomes by employing the pH-gradient method (interior pH of liposomes 9.5;
      exterior pH 5.0-5.9). A maximum of 14% of monensin could be entrapped in stealth
      liposomes by this method. The stealth liposomes could be successfully freeze
      dried having mean particle size varying between 197 and 223 nm. The stealth
      liposomes were conjugated to anti-My9 monoclonal antibody (targeted against CD 33
      antigen) by a disulfide linkage with almost full retention of immunoreactivity.
      The method of conjugation of liposomes with the antibody did not alter the
      particle size of liposomes and resulted in only 10% leakage of monensin. In-vitro
      cytotoxicity studies showed that antibody-conjugated monensin liposomes (3.5x10(
      8) M monensin) potentiated the cytotoxicity of anti-My9 immunotoxin by a factor
      of 2070, in comparison to 360-fold potentiation observed with unconjugated
      monensin liposomes against human HL-60 promyelocytic leukemia cells. These
      results indicate that it is possible to enhance the in-vitro cytotoxicity of
      immunotoxin by several folds using antibody-conjugated monensin liposomes.

PMID- 11578744
TI  - Effect of protein molecular weight on release from micron-sized PLGA
      microspheres.
AB  - This study investigates the effect of protein molecular weight on release
      kinetics from polymeric microspheres (1-3 microm). Proteins were encapsulated at
      high and low loadings in poly(lactic-co-glycolic acid) (PLGA) by a phase
      inversion technique. Mechanism of release from this type of microsphere appeared
      to be dependent on protein molecular weight for microspheres with low loadings
      (0.5-1.6%), while independent of protein molecular weight for microspheres with
      high loadings (4.8-6.9%). At low loadings, release of larger proteins was
      dependent on diffusion through pores for the duration of the study, while smaller
      proteins seemed to depend on diffusion through pores initially and on degradation
      at later times. Following an initial diffusion phase from low loaded
      microspheres, lysozyme and carbonic anhydrase, the two smallest proteins,
      exhibited lag phases with curtailed protein release followed by a phase of
      increased protein release between 4 and 8 weeks, a phenomenon not evident for
      larger proteins. It appears that by 8 weeks, PLGA had degraded enough to allow
      additional release of smaller proteins which were entrapped efficiently within
      the microspheres. Higher loaded microspheres, which have more interconnecting
      channels, did not exhibit the pronounced shift from diffusion-based to polymer
      degradation-based release seen with the lower loaded microspheres. Interestingly,
      microspheres encapsulating large proteins maintained sustained release rates for
      56 days.

PMID- 11578745
TI  - Protein release profiles and morphology of biodegradable microcapsules containing
      an oily core.
AB  - The protein release profiles and the morphology of poly(D,L-lactide-co-glycolide)
      (PLG) and poly(epsilon-caprolactone) (PCL) microcapsules were investigated. The
      microcapsules were prepared by the (oil(1)-in-oil2)-in-water emulsion solvent
      evaporation method using bovine serum albumin (BSA) as a model protein. The
      internal and external morphologies of the microcapsules were examined using a
      light microscope, scanning electron microscope and a laser scanning confocal
      microscope. A Coulter counter was used to determine particle size and particle
      size distribution. Protein quantitation and molecular integrity were performed by
      the bicinchoninic acid protein assay micro-method and SDS-PAGE, respectively.
      Microcapsules with a polymeric wall surrounding an oily core containing the
      protein were formed. The encapsulation efficiency (39-96%) for PLG and (13-90%)
      for PCL increased with polymer molecular weight and particle volume mean diameter
      (Vmd). Vmd ranged from 87-128 to 42-157 microm for PLG and PCL, respectively. The
      protein release profile for PLG microcapsules was either continuous or
      irregularly pulsatile depending on particle morphology and was completed after
      cavity breakdown. However, that of PCL microcapsules was essentially irregularly
      pulsatile and was completed after a longer period of time without cavity
      breakdown but with significant swelling. There was no detectable cleavage of the
      protein during 6 months storage of PLG and PCL microcapsules at 4 degrees C.
      Furthermore, insignificant degradation of protein occurred during in vitro
      release from PCL microcapsules. In contrast, significant degradation occurred in
      PLG microcapsules. This approach to microencapsulation of a protein may be
      promising for the controlled delivery of protein vaccines, and the oil core may
      enhance the immunogenicity of some weak subunit vaccine candidates.

PMID- 11578746
TI  - Studies on the effect of pH on the lipoidal route of penetration across stratum
      corneum.
AB  - The effect of pH on the excised skin permeability towards two model lipophilic
      compounds was studied in the range of pH 1.0-10.0 and 1.0-12.0, for
      hydrocortisone and testosterone, respectively. Suspensions of the model compounds
      in appropriate buffers (0.1-0.2 M) were applied to the intact skin, delipidized
      skin, skin pretreated with Azone or sodium lauryl sulfate solution and the
      percutaneous penetration was observed for 28 h. Within the studied pH range, up
      to pH 11.0 no change in the penetration through the skin and skin accumulation
      was observed for both compounds. Significant, 3-4-fold, increase of penetration
      of testosterone was noted only at pH 12.0, however the change was neither fast
      not progressing with time. None of the pretreatment procedure influenced the
      observed relationship between pH and skin permeability. It is concluded that the
      lipoidal route of penetration is not affected by solutions at pH within the range
      1.0-11.0.

PMID- 11578747
TI  - Development and release characterization of hyaluronan-doxycycline gels based on
      metal coordination.
AB  - A simple mixing with hyaluronan (HA), doxycycline (DC) and divalent metal cation
      in an aqueous solution enabled a thermoreversible water-soluble gel to form. For
      the cross-linking, two kinds of interactions were supposed. One was an
      electrostatic interaction between a positively charged group in DC and a
      negatively charged carboxyl function of HA, and the other was a chelation at the
      phenolic diketone moiety in DC. Since the gel was formed physically, the critical
      polymer concentration for gelation was present, and it was about 0.05% for HA
      with a molecular weight of 1.6x10(6). The hydrogel would be formed holding water
      in the HA entanglement network when DCs on HA chains made coordinate bonds
      through metal chelation. By changing the mixing ratio, two types of gels with
      different characteristics in drug release could be prepared. One was a gel with
      zero-order release prepared by mixing the same amount of HA and DC in equivalent.
      The other was a gel indicating Fickian diffusion-type release by mixing more DC
      than HA. Further, by controlling the absolute concentration of HA and DC, or the
      molecular weight of HA, some gels with desired release profiles could be
      prepared.

PMID- 11578748
TI  - Galactosylated chitosan-graft-poly(ethylene glycol) as hepatocyte-targeting DNA
      carrier.
AB  - Lactobionic acid bearing galactose group was coupled with chitosan for liver
      specificity, and poly(ethylene glycol) (PEG) was grafted to galactosylated
      chitosan (GC) for stability in water and enhanced cell permeability. Complex
      formation of galactosylated chitosan-graft-PEG (GCP)/DNA complexes was confirmed
      by agarose gel electrophoresis. Compared to GC/DNA complex, the stability of
      GCP/DNA complex could be enhanced. Particle sizes of GCP/DNA complexes decreased
      as the charge ratio of GCP to DNA increased and had a minimum value around 27 nm
      at the charge ratio of 5. Conformational change of DNA did not occur after
      complex formation with GCP compared to conformation of DNA itself. GCP/DNA
      complexes were only transfected into Hep G2 having asialoglycoprotein receptors
      (ASGR), indicative of specific interaction of ASGR on cells and galactose ligands
      on GCP.

PMID- 11578749
TI  - Absorption of water-soluble compounds with different molecular weights and.
AB  - The absorption of water soluble compounds with different molecular weights, such
      as phenol red (MW 354), trypan blue (MW 960), fluorescein isothiocyanate
      dextrans, (MW 4400 and 9100) was studied in the lung, nasal cavity, buccal
      cavity, small and large intestine of rats. For all the compounds, maximal
      absorption was observed when administered to the lung. The rank order of
      absorption of each compound from various administration sites was lung>small
      intestine> or =nasal cavity> or =large intestine> or =buccal cavity. In addition,
      the relationship between logarithm absorption % of the compounds from various
      administration sites and logarithm molecular weights of these compounds was
      examined. The absorption of compounds gradually decreased with increasing
      molecular weight for each site of administration. Moreover, the absorption of
      [Asu1.7]-eel calcitonin (ECT) from these sites and the effect of 10 mM sodium
      glycocholate, an absorption enhancer, on its absorption were also investigated in
      rats. When ECT alone was administered into these sites, the lung had the best
      absorption site of ECT, followed by the nasal cavity, the large intestine, the
      small intestine and the buccal cavity. Therefore, the absorption of ECT was also
      dependent on the administration site, although the rank order of absorption % of
      ECT was different from the other compounds. Sodium glycocholate (NaGC) remarkably
      increased ECT absorption from the small intestine, while we found marginal
      increase in its absorption from the lung even in the presence of NaGC. These
      findings provided useful fundamental information that might aid in the selection
      of administration routes for drugs of differing molecular weights including
      peptide drugs as far as the degree of drug absorption is concerned.

PMID- 11578750
TI  - Bioethics in medical research.

PMID- 11578751
TI  - The molecular bases of Alzheimer's disease and other neurodegenerative disorders.
AB  - Alzheimer's disease, the cause of one of the most common types of dementia, is a
      brain disorder affecting the elderly and is characterized by the formation of two
      main protein aggregates: senile plaques and neurofibrillary tangles, which are
      involved in the process leading to progressive neuronal degeneration and death.
      Neurodegeneration in Alzheimer's disease is a pathologic condition of cells
      rather than an accelerated way of aging. The senile plaques are generated by a
      deposition in the human brain of fibrils of the beta-amyloid peptide (Abeta), a
      fragment derived from the proteolytic processing of the amyloid precursor protein
      (APP). Tau protein is the major component of paired helical filaments (PHFs),
      which form a compact filamentous network described as neurofibrillary tangles
      (NFTs). Experiments with hippocampal cells in culture have indicated a
      relationship between fibrillary amyloid and the cascade of molecular signals that
      trigger tau hyperphosphorylations. Two main protein kinases have been shown to be
      involved in anomalous tau phosphorylations: the cyclin-dependent kinase Cdk5 and
      glycogen synthase kinase GSK3beta. Cdk5 plays a critical role in brain
      development and is associated with neurogenesis as revealed by studies in brain
      cells in culture and neuroblastoma cells. Deregulation of this protein kinase as
      induced by extracellular amyloid loading results in tau hyperphosphorylations,
      thus triggering a sequence of molecular events that lead to neuronal
      degeneration. Inhibitors of Cdk5 and GSK3beta and antisense oligonucleotides
      exert protection against neuronal death. On the other hand, there is cumulative
      evidence from studies in cultured brain cells and on brains that oxidative stress
      constitutes a main factor in the modification of normal signaling pathways in
      neuronal cells, leading to biochemical and structural abnormalities and
      neurodegeneration as related to the pathogenesis of Alzheimer's disease. This
      review is focused on the main protein aggregates responsible for neuronal death
      in both sporadic and familial forms of Alzheimer's disease, as well as on the
      alterations in the normal signaling pathways of functional neurons directly
      involved in neurodegeneration. The analysis is extended to the action of
      neuroprotective factors including selective inhibitors of tau phosphorylating
      protein kinases, estrogens, and antioxidants among other molecules that
      apparently prevent neuronal degeneration.

PMID- 11578752
TI  - Standardization of micro-enzyme-linked immunosorbent assay (ELISA) and Western
      blot for detection of Trypanosoma cruzi antibodies using extracts from Mexican
      strains as antigens.
AB  - BACKGROUND: This report describes two assays for the detection of anti
      Trypanosoma cruzi antibodies using Mexican strains of the parasite and the
      concordance with two assays previously evaluated at the Instituto Nacional de
      Cardiologia Ignacio Chavez in Mexico City. METHODS: Micro-enzyme-linked
      immunosorbent assay (ELISA) and Western blot were used for the detection of T.
      cruzi antibodies with a total extract of epimastigote from Ninoa and Queretaro,
      which are Mexican strains of T. cruzi. To standardize these methods, a total of
      246 serum samples was used. In addition, sera from six confirmed Mexican chronic
      individuals in the asymptomatic phase were also used for comparison with the
      Argentinean antigen. RESULTS: ELISA was 100% specific in that no false positive
      results were found with sera of both healthy individuals and non-Chagasic
      cardiopaths. Sera from individuals infected with Leishmania sp. showed
      approximately 16% of cross-reaction with ELISA. The test showed a positive
      predictive value of 90% and a negative predictive value of 100%. Western blot was
      also a highly sensitive test for detecting chronic Chagasic symptomatic patients
      from Mexico because no false negative results were obtained. Furthermore, it was
      possible to use Western blot to detect seven immunodominant antigens of
      approximately 30, 32, 40, 42, 65, 70, and 83 kDa. Concordance with two previous
      standardized tests at the Instituto Nacional de Cardiologia showed a Kappa index
      of 0.96, indicating high concordance between the results obtained at these two
      laboratories. Finally, ELISA using Ninoa antigen extract was more sensitive than
      ELISA with an Argentinean extract, which failed to detect individuals in the
      chronic asymptomatic phase (undetermined phase) of infection. CONCLUSIONS: This
      study indicates that ELISA and Western blot using Ninoa and/or Queretaro extracts
      of T. cruzi as antigens are useful tools in the detection of individuals who have
      been exposed to T. cruzi both in the undetermined/asymptomatic and symptomatic
      phases. More concordance studies such as this are recommended to obtain an
      accurate Chagas diagnostic test and to determine the real prevalence of this
      disease in Mexico.

PMID- 11578753
TI  - The hypotensive effect of BMY 7378 is antagonized by a silent 5-HT(1A) receptor
      antagonist: comparison with 8-hydroxy-dipropylamino tetralin.
AB  - BACKGROUND: Stimulation of central 5-HT(1A) receptors produces bradycardia and
      diminishes blood pressure in conscious or anesthetized rats. Our objective was to
      investigate the effects on blood pressure and heart rate of the partial 5-HT(1A)
      receptor agonist and selective alpha1D-adrenoceptor antagonist BMY 7378 (8-[2-[4
      (2-methoxyphenyl)-1-piperazinyl] ethyl]-8-azaspiro [4.5] decane-7,9 dione
      hydrochloride) compared to the full 5-HT(1A) receptor agonist 8-OH-DPAT (8
      hydroxy-dipropylamino tetralin) in adult anesthetized rats. METHODS: Male Wistar
      rats of 6 months of age were exposed intravenously (i.v.) to increasing doses of
      BMY 7378 or 8-OH-DPAT in the absence and presence of WAY 100635. Blood pressure
      and heart rate were continuously recorded. RESULTS: BMY 7378 induced a decrease
      in blood pressure with no apparent change in heart rate compared to basal values,
      while 8-OH-DPAT decreased both hemodynamic parameters. BMY 7378 hypotensive
      effect was antagonized by the selective, silent 5-HT(1A) receptor antagonist WAY
      100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-(2-pyridinyl)
      cyclohexanecarboxamide trihydrochloride). However, a remnant yet significant
      hypotensive effect was not blocked by the antagonist. In contrast, 8-OH-DPAT
      actions were completely blocked by WAY 100635. CONCLUSIONS: Data suggest that BMY
      7378 cardiovascular effects are related to activation, as a full agonist, of
      central 5-HT(1A) receptors in adult rats; however, participation of other systems
      such as vascular alpha1-adrenoceptors in cardiovascular function is suggested.

PMID- 11578754
TI  - Oral theophylline changes renal carnitine palmitoyltransferase activity in rats.
AB  - BACKGROUND: Carnitine plays a critical role in lipid metabolism. Carnitine
      deficiency may adversely affect the oxidation of fatty acids and further
      aggravate abnormal lipid metabolism. Our objective was to investigate the effect
      of theophylline on the activity of carnitine palmitoyltransferase (CPT) in renal
      tissues of rats for 5-week-interval treatments. METHODS: The study was a
      randomized, controlled animal study. Theophylline was given at 100 mg/kg body
      weight (b.w.)/day and effects were monitored after a treatment period of between
      1 and 5 weeks. RESULTS: Theophylline treatment caused a significant increase in
      renal CPT activity as compared to either control or placebo groups. Moreover, the
      results showed positive correlations between the renal concentration of long
      chain acylcarnitine (LC), activity of CPT, urinary excretion of acylcarnitine
      (AC), and plasma concentration of LC (p <0.01), respectively. CONCLUSIONS: The
      observed changes in activity of renal CPT might be due to the result from
      theophylline-enhanced mobilization of lipid from adipose tissues that
      consequently stimulated an increased carnitine transport into the renal tissues
      to form palmitoylcarnitine groups for subsequent beta-oxidation inside the
      mitochondria. Thus, these accumulations of palmitoylcarnitine groups in
      mitochondria may increase the catalytic action of CPT.

PMID- 11578756
TI  - Altered action potential of myocardial cells from mouse fetuses with trisomy 16:
      a model of Down syndrome.
AB  - BACKGROUND: Trisomy 21 in humans and trisomy 16 in mice (a model of Down
      syndrome) are associated with increases in rates of depolarization and
      repolarization and decreases in duration of action potential of neurons, due to
      overexpressing protein subunits of Na(+) and K(+) channels in a gene dose
      dependent manner. These chromosomes also have genes for voltage-gated Na(+) and
      K(+) channels expressed by myocardial cells. Thus, it would be expected that
      heart cells would have alterations in their action potentials similar to those
      found in neurons in both aneuploidies. METHODS: Myocardial cells from normal and
      trisomy 16 mouse fetuses were compared in relation to their electrical membrane
      properties using intracellular microelectrodes. RESULTS: At 13 and 17 days of
      gestation, trisomic cells, as compared with control cells, had higher amplitude
      and rates of depolarization and repolarization, with lower duration of plateau of
      action potential at 25, 50, and 75% of repolarization. This suggests that Ca(2)+
      influx is reduced in trisomic cells, which could impair Ca(2)+-dependent fetal
      myocardial functions (i.e., contractility or matrix secretion). CONCLUSIONS:
      Myocardial cells of Ts-16 mice showed electrophysiologic alterations
      qualitatively similar to those observed in trisomic neurons, in agreement with
      the gene dose-dependent hypothesis (see Introduction).

PMID- 11578755
TI  - Uptake of porcine rubulavirus (LPMV) by PK-15 cells.
AB  - BACKGROUND: The porcine virus denominated La Piedad Michoacan Virus (LPMV) is a
      member of the family Paramyxoviridae and is the cause of a disease in pigs
      present only in Mexico. The disease is characterized by meningoencephalitis and
      respiratory distress in young pigs, epididymitis and orchitis in boars, and
      reproductive failure and abortion in sows. METHODS: The cytopathology,
      morphology, and distribution of the hemagglutination neuraminidase (HN) and
      nucleoprotein (NP) proteins of LPMV were investigated following inoculation into
      PK-15 cells. The cytopathic effect was characterized by cytoplasmic vacuolation
      and the formation of syncytia and cytoplasmic inclusion bodies. RESULTS: In
      immunofluorescence assays using a monoclonal antibody (MAb) against the HN
      protein at 5-60 min post-infection (early infection), a diffuse
      immunofluorescence was observed near the cell membrane and adjacent to the
      nuclear membrane. At 24 h post-infection (late infection), a dust-like
      immunofluorescence was observed throughout the cytoplasm. LPMV-infected cells
      incubated with the MAb against the NP protein showed punctate cytoplasmic
      fluorescence during the early stages of infection. At the late infection stage,
      these fluorescent particles became larger and were seen predominantly in the
      cytoplasm of syncytia. This pattern was also apparent by immunohistochemical
      labeling and immunogold electron microscopy. The latter technique revealed that
      HN protein was diffusely distributed throughout the cytoplasm. When using the MAb
      against the NP protein, nucleocapsid organization was the most prominent feature
      and resulted in the formation of cytoplasmic inclusion bodies visible by light
      and electron microscopy. Immunogold labeling of purified nucleocapsids was shown
      by electron microscopy. Virus particles and nucleocapsids were morphologically
      similar to members of the Paramyxoviridae family. CONCLUSIONS: The morphologic
      characteristics of the virions and the distribution patterns of the HN and NP
      proteins in PK-15 infected cells indicate that the mechanisms of LPMV replication
      are generally similar to those of the members of the Paramyxoviridae family.

PMID- 11578757
TI  - Biochemical characteristics of the gamma-aminobutyric acid system in the
      insulinoma cell lines HIT-T15, RIN-m5F, betaTC3, and comparison with rat brain.
AB  - BACKGROUND: gamma-aminobutyric acid (GABA) is the most abundant inhibitory
      neurotransmitter in the mammalian brain. Both GABA and its synthesizing enzyme, L
      glutamate decarboxylase (GAD), are also present in the insulin-secreting
      pancreatic beta cells, in which its physiologic role is unclear. We have studied
      several aspects of the GABA system in the insulinoma cell lines HIT-T15, RIN-m5F,
      and betaTC3 in comparison with rat brain tissue. METHODS: Insulinoma cell lines
      and embryonic rat brain cortex neurons were cultured. GAD activity was determined
      by a radioenzymatic method and the presence of GAD(67) protein was assessed by
      immunocytochemistry. Amino acid content and the effect of different conditions on
      the release of endogenous GABA were measured by HPLC and fluorometric detection
      after o-phthaldialdehyde derivatization. [3H]GABA was used for measuring the
      uptake of the amino acid in the insulinoma cultures and in rat forebrain
      synaptosomes. RESULTS: The three insulinoma lines possess GABA and GAD activity
      at levels of approximately 20% compared with adult rat brain cortex. Dissimilar
      from the latter, in insulinoma cultures enzyme activity was not enhanced by
      addition of an excess of the coenzyme pyridoxal-5'-phosphate. Immunocytochemical
      visualization of GAD showed that the cells in both neuronal cultures and
      insulinoma lines were GAD(67)-positive, similar to Purkinje cell somata of adult
      rat cerebellar cortex. [3H]GABA uptake in the cell lines was approximately 10% of
      that in rat forebrain synaptosomes and showed less ionic and temperature
      dependence. In both cultured cerebral neurons and RINm5F cells, the addition of
      arginine induced the release of GABA, whereas neither high K(+) concentration nor
      glucose had any effect. CONCLUSIONS: The insulinoma cell lines studied possess
      the same GAD(67) form of the enzyme present in brain. RIN line cells are capable
      of transporting glutamate. In these cells as well as in cultured cortical
      neurons, arginine stimulates the release of GABA and glutamate probably as the
      result of its electrogenic transport. Insulinoma cell lines may therefore be
      useful to study GABA metabolism and function in pancreatic beta cells.

PMID- 11578758
TI  - The influence of altitude in bronchial asthma.
AB  - BACKGROUND: Some asthmatic children living in mountain areas experience
      significant improvement in daily symptoms and in the degree of bronchial
      obstruction. The aim of this study is to investigate the effect of altitude on
      the prevalence and morbidity of childhood bronchial asthma. METHODS: A
      questionnaire regarding the history and symptoms of asthma was distributed to 874
      children aged 6-12 years, to be completed by their parents with the help of their
      pediatrician. A total of 583 children lived at sea level, 180 at an altitude
      between 501 and 800 meters, and 111 at an altitude between 801 and 1,200 meters.
      All children with recurrent cough, shortness of breath, wheezing, and a history
      of bronchial asthma were considered to have bronchial asthma. RESULTS: The
      prevalence of childhood bronchial asthma in the mountains (800-1,200 meters) was
      twice as low as that at sea level (15.8% of children) (p <0.01). Parental smoking
      was more frequent in children who lived at sea level than in the mountains.
      Additionally, consumption of fish and oranges was more frequent at sea level.
      Children with asthma who lived in the mountains were absent fewer days from
      school per year (0.2) and had fewer nights with dyspnea per year (0.5) than
      asthmatic children who lived at sea level (1.6 days and 25 nights, respectively).
      CONCLUSIONS: Bronchial asthma in children who live at high altitudes is
      characterized by low prevalence and low morbidity.

PMID- 11578759
TI  - Biochemical analysis of arginase and ornithine carbamoyltransferase in human
      vitreous humor.
AB  - BACKGROUND: The presence of arginase and ornithine carbamoyltransferase (OTC'ase)
      enzymes in human vitreous humor after death was investigated in this study. To
      the best of our knowledge, there is no prior report on the activity of arginase
      or ornithine carbamoyltransferase in human vitreous humor. METHODS: The presence
      of arginase and OTC'ase activities were examined in the human vitreous humor of
      19 samples. Spectrophotometric methods were used to determine activities of
      arginase and OTC'ase. RESULTS: Arginase activity was detected in human vitreous
      humor, whereas OTC'ase activity was below the detection limit. Therefore, we
      focused on biochemical analysis of arginase in human vitreous humor. Kinetic
      properties of arginase activity in vitreous humor were optimized. In contrast to
      other arginases, optimal preincubation temperature and pH were 40 degrees C and
      8.8, respectively. Km of vitreous arginase for L-arginine was 6 mM. Preincubation
      of the enzyme with Mn(2)+ ions caused a significant increase (33%) in arginase
      activity. CONCLUSIONS: The activity and presence of arginase as well as its
      kinetics in human vitreous are documented in this study. Biochemical functions
      and the importance of arginase in vitreous humor are not well understood.
      However, its presence may be explained by means of its involvement in polyamine
      biosynthesis as observed in the other extrahepatic tissues.

PMID- 11578760
TI  - Antioxidant effects of D002 on the in vitro susceptibility of whole plasma in
      healthy volunteers.
AB  - BACKGROUND: It has been recently shown that oral administration of D002, a
      mixture of higher aliphatic primary alcohols isolated from beeswax, inhibits rat
      microsomal lipid peroxidation. This justified the present attempt to investigate
      whether D002 also exerts antioxidant effects in humans. METHODS: The effects of
      D002 on lipid peroxidation were studied in a double-blind, randomized, placebo
      controlled trial conducted in 50 healthy volunteers. Unfractionated plasma
      samples at baseline and at 12 weeks were subjected to in vitro copper-induced
      lipid peroxidation and conjugated diene generation was monitored by changes of
      optical density. RESULTS: The oral treatment with D002 (50 mg/day) not only
      significantly prolonged (p <0.001) lag time before the onset of conjugated diene
      formation compared with that of baseline but also increased (p <0.05) lag phase
      when compared with placebo group. In fact, in the D002 group the lag-phase of
      oxidation was prolonged 1.5-fold. D002 oral treatment decreased TBARS and
      increased plasma total antioxidant status (TAS) (p <0.01). CONCLUSIONS: Because
      prooxidant states have been linked to normal senescence and some age-related
      diseases, the present data suggest that D002 may find a use in preventing age
      related diseases as a dietary natural antioxidant supplement.

PMID- 11578761
TI  - Hepatitis C virus RNA (HCV-RNA) in blood donors and family members seropositive
      for anti-HCV antibodies.
AB  - BACKGROUND: Non-A, non-B virus is responsible for 75-90% of all cases of blood
      transfusion-related hepatitis. The aim of this work was to determine hepatitis C
      virus RNA (HCV-RNA) in a group of blood donors and their household contacts.
      Serotype and genotype of the isolates were also studied. METHODS: HCV antibodies
      were investigated in 44,588 blood donors with a commercial immunoassay. Forty
      four seropositive donors and 72 household members were further studied.
      Quantitative analysis of viral RNA was performed with Amplicor HCV 2.0 test,
      while genotype was determined by INNO-LiPA test and serotype with Murex HCV test.
      RESULTS: Among the 44,588 donors studied, 333 (0.74%) were positive for anti-HCV.
      Viral RNA was found in 35 (80%) of the 44 seropositive cases studied. Among the
      72 household members, HCV antibodies were detected in six (8.3%) and HCV-RNA in
      four of these individuals. Serotype 1 and genotype 1 were the most frequent types
      detected (48 and 64%, respectively). The genotype in the blood donor matched that
      of his seropositive family member in four of six cases. CONCLUSIONS: Our results
      suggest that intrafamilial transmission of HCV may occur and we stress the need
      to study household members of seropositive blood donors, as they have a high risk
      of infection. In this community, genotype 1 is the most prevalent type in blood
      donors and family members.

PMID- 11578762
TI  - Obesity, diabetes, hypertension, and tobacco consumption in an urban adult
      Mexican population.
AB  - BACKGROUND: The aim of this study was to describe the prevalence of some of the
      main coronary risk factors in an open Mexican adult population. METHODS: This is
      a cross-sectional study that includes individuals from eight different cities.
      Except for Mexico City, all centers were located in medium-sized cities ranging
      from 1 to 5 million inhabitants. Eligible subjects were adults 20 years of age or
      older. Exclusion criteria included subjects seeking medical attention due to an
      acute illness or individuals unable to provide the requested information or
      written consent to participate in the study. Men (n = 567) and women (n = 1,018)
      were included. A previously validated interview was conducted. A questionnaire
      assessed demographic and lifestyle factors. Capillary glucose concentration and
      blood pressure were obtained. Remarkably, 40% of the population had a body mass
      index (BMI) between 25 and 29.9 kg/m(2); an additional 28% had a BMI >30 kg/m(2).
      A large proportion of the individuals had abdominal fat distribution (62% of men
      and 81% of women). At the time of the evaluation, 30% of men and 18% of women
      were regular smokers. RESULTS: Blood pressure >140/90 mmHg was found in 29.4% of
      the population. Less than one half of the subjects had a previous measurement of
      plasma cholesterol (47%) or triglycerides (42%). The prevalence of diabetes was
      9.02%. A significant percentage of these subjects were <40 years of age (18.8% of
      the diabetic population). CONCLUSIONS: The prevalence of obesity, diabetes, and
      hypertension in the population reported here is among the highest reported in
      Mexican populations.

PMID- 11578763
TI  - Prevalence of G-6-PD deficiency in the Croatian Adriatic Coast population.
AB  - BACKGROUND: The objective of this study was to determine the prevalence of
      glucose-6-phosphate dehydrogenase (G-6-PD) deficiency among the population of the
      Croatian Adriatic Coast, part of the Mediterranean basin. METHODS: The
      fluorescent spot test was used to screen 2,726 randomly selected high school
      students in the Croatian Adriatic coastal area. Fluorescence readings were
      performed at the beginning and at 3, 6, 10, and 25 min of incubation. Results
      were classified into the following three groups: bright fluorescence (BF), weak
      fluorescence (WF), and no fluorescence (NF). All NF and WF samples at 3 min were
      quantitatively measured using the spectrophotometric method. RESULTS: Twelve
      persons, 10 boys and 2 girls, were found to be deficient in G-6-PD, rendering a
      0.44% prevalence of G-6-PD deficiency. All NF samples at fluorescent spot test
      were G-6-PD-deficient. WF at 3 min of the incubation period was present in 33
      (1.2%) subjects, and only 2 (6%) were true positive. Fluorescence reading at 10
      min of incubation omits five (41%) of the G-6-PD deficient samples. CONCLUSIONS:
      Prevalence of G-6-PD deficiency in the Croatian Adriatic coastal population is
      0.44%. Fluorescent spot test for moderate enzyme deficiency is reliable in early
      fluorescence reading.

PMID- 11578764
TI  - Helicobacter pylori and other enteric bacteria in freshwater environments in
      Mexico City.
AB  - BACKGROUND: Helicobacter pylori infection is common in the Mexican population;
      however, sources, routes, and risk factors for infection as well as mode of
      transmission remain unclear. METHODS: H. pylori was detected by polymerase chain
      reaction (PCR) technique in three aquatic systems located in the Mexico City
      area. In addition, microbiologic cultures and physicochemical parameters were
      measured. The systems were sampled over an 18-month period (1997-1999), resulting
      in a total of 212 samples for the different analyses. RESULTS: Twenty-one percent
      of the samples (16/77) were positive for H. pylori; of these, 42% (5/12) were
      confirmed for cagA gene detection by PCR hybridization. Microbiologic samples (n
      = 74) yielded Aeromonas hydrophila, Aeromonas caviae, Aeromonas veronii, and
      Vibrio fluvialis. In the samples for physicochemical analyses (n = 61), low
      concentrations of dissolved oxygen were detected and residual chlorine was less
      than the inactivation dose, both providing conditions for potential survival of
      H. pylori and other enteric pathogens in these environments. CONCLUSIONS: The
      results of this study suggest that, in Mexico City, water used for human
      consumption and irrigation may play an important role as a vehicle in the
      transmission of H. pylori as well as infection by other known enteric pathogens.

PMID- 11578765
TI  - Vaccination against hepatitis A in children aged 12 to 24 months [corrected].
AB  - BACKGROUND: Current hepatitis A vaccines are either licensed for children >2
      years of age, as in the U.S. or Chile, or >1 year of age, as in Europe and other
      parts of the world. Recent recommendations for immunization against hepatitis A
      have included routine vaccination of children in areas or regions of higher
      endemicity. However, data on hepatitis A vaccination in toddlers aged between 1
      and 2 years are scarce. METHODS: This open clinical study investigated the
      reactogenicity and immunogenicity of two doses (0, 6-month schedule) of an
      inactivated hepatitis A vaccine (Havrix pediatric, Glaxco SmithKline Biologicals,
      Rixensart, Belgium) in 120 seronegative children aged 12-24 months. RESULTS: Pain
      at the injection site and irritability were the most frequently reported local
      and general symptoms, respectively. No serious adverse events related to the
      study vaccine were reported. One month after the first dose, all but one subject
      had antibodies against hepatitis A with a GMT of 159 mIU/mL. After the booster
      dose, all had antibodies with a GMT of 2,939 mIU/mL. CONCLUSIONS: Our data show
      that the inactivated hepatitis A vaccine was well tolerated by these toddlers and
      that the vaccine elicits a good immune response.

PMID- 11578766
TI  - Ethical principles in human subject research.

PMID- 11578767
TI  - Glia and Alzheimer's disease.

PMID- 11578768
TI  - Microglial chemotaxis, activation, and phagocytosis of amyloid beta-peptide as
      linked phenomena in Alzheimer's disease.
AB  - Microglia are widely held to play important pathophysiologic roles in Alzheimer's
      disease (AD). On exposure to amyloid beta peptide (A beta) they exhibit
      chemotactic, phagocytic, phenotypic and secretory responses consistent with
      scavenger cell activity in a localized inflammatory setting. Because AD
      microglial chemotaxis, phagocytosis, and secretory activity have common, tightly
      linked soluble intermediaries (e.g., cytokines, chemokines), cell surface
      intermediaries (e.g., receptors, opsonins), and stimuli (e.g., highly inert A
      beta deposits and exposed neurofibrilly tangles), the mechanisms for microglial
      clearance of A beta are necessarily coupled to localized inflammatory mechanisms
      that can be cytotoxic to nearby tissue. This presents a critical dilemma for
      strategies to remove A beta by enhancing micoglial activation--a dilemma that
      warrants substantial further investigation.

PMID- 11578770
TI  - Two-dimensional gel analysis of secreted proteins induced by interleukin-1 beta
      in rat astrocytes.
AB  - Interleukin-1 beta (IL-1 beta) is a pro-inflammatory cytokine produced in the
      brain by endogenous microglial cells responding to injury. Levels of IL-1 beta
      are elevated in several neurodegenerative disorders, including Alzheimer's
      disease. IL-1 beta, which can act as a mitogen for astrocytes, also elicits the
      expression and secretion of multiple factors and paracrine 'second messengers'
      such as other cytokines, nerve growth factor, prostaglandins and nitric oxide
      that may in turn modulate neuronal and glial responses to injury. Utilizing
      giant, high-resolution two-dimensional gel electrophoresis, we have sought to
      more fully define the potential range of protein mediators that are secreted by
      astrocytes treated with IL-1 beta. In cultured rat astrocytes, we observe
      dramatic increases in the secretion of eight different protein species after 24 h
      of treatment with human recombinant IL-1 beta (1 U/ml). Seven of the proteins are
      also induced by tumor necrosis factor-alpha or basic fibroblast growth factor.
      Based on immunoprecipitation with specific antisera, we have identified three of
      these proteins as plasminogen activator inhibitor type-1, ceruloplasmin, and
      complement component C3. The identities of the other proteins, including the IL-1
      beta-specific induction, are currently unknown. Characterization of these
      downstream modulators of IL-1 beta action complements gene-based approaches and
      will provide a better understanding of astrocyte responses to injury as well as
      markers for astrocyte activation in neurodegenerative diseases.

PMID- 11578769
TI  - Interleukin-1 promotion of MAPK-p38 overexpression in experimental animals and in
      Alzheimer's disease: potential significance for tau protein phosphorylation.
AB  - Activated (phosphorylated) mitogen-activated protein kinase p38 (MAPK-p38) and
      interleukin-1 (IL-1) have both been implicated in the hyperphosphorylation of
      tau, a major component of the neurofibrillary tangles in Alzheimer's disease.
      This, together with findings showing that IL-1 activates MAPK-p38 in vitro and is
      markedly overexpressed in Alzheimer brain, suggest a role for IL-1-induced MAPK
      p38 activation in the genesis of neurofibrillary pathology in Alzheimer's
      disease. We found frequent colocalization of hyperphosphorylated tau protein (AT8
      antibody) and activated MAPK-p38 in neurons and in dystrophic neurites in
      Alzheimer brain, and frequent association of these structures with activated
      microglia overexpressing IL-1. Tissue levels of IL-1 mRNA as well as of both
      phosphorylated and non-phosphorylated isoforms of tau were elevated in these
      brains. Significant correlations were found between the numbers of AT8- and MAPK
      p38-immunoreactive neurons, and between the numbers of activated microglia
      overexpressing IL-1 and the numbers of both AT8- and MAPK-p38-immunoreactive
      neurons. Furthermore, rats bearing IL-1-impregnated pellets showed a six- to
      seven-fold increase in the levels of MAPK-p38 mRNA, compared with rats with
      vehicle-only pellets (P<0.0001). These results suggest that microglial activation
      and IL-1 overexpression are part of a feedback cascade in which MAPK-p38
      overexpression and activation leads to tau hyperphosphorylation and
      neurofibrillary pathology in Alzheimer's disease.

PMID- 11578771
TI  - Effect of cytokines, dexamethasone and the A/T-signal peptide polymorphism on the
      expression of alpha(1)-antichymotrypsin in astrocytes: significance for
      Alzheimer's disease.
AB  - Proinflammatory cytokines and acute phase proteins, such as alpha(1)
      antichymotrypsin, are over expressed in microglia and astrocytes in brain regions
      with abundant mature amyloid plaques, suggesting a glial cell-led brain acute
      phase response in the Alzheimer neuropathology. In this paper, we show that
      alpha(1)-antichymotrypsin gene expression in human astrocytes is elevated by
      interleukin-1 and interleukin-6, and further enhanced by glucocorticoid, while
      the homologous contrapsin gene in rat astrocytes is unaffected by these
      cytokines. These distinct gene regulation mechanisms might help to explain the
      differential susceptibility of humans and rodents to amyloid formation of the
      Alzheimer's type. In addition, we demonstrate that the alpha(1)-antichymotrypsin
      A-allele that encodes a different signal peptide and is a suggested risk factor
      for Alzheimer's disease gives rise to a reduced level of immature alpha(1)
      antichymotrypsin in transfected cells. The physiological result would be an
      enhanced ability of the A-encoded alpha(1)-antichymotrypsin protein to become
      secreted and promote extracellular amyloid formation. We discuss our findings in
      terms of a model in which cytokine-induced alpha(1)-antichymotrypsin synthesis in
      astrocytes constitutes a specific inflammatory pathway that accelerates the
      development of Alzheimer's disease and could at least partly underlie the
      regional specificity and species restriction of the neuropathology.

PMID- 11578772
TI  - CD40 signaling and Alzheimer's disease pathogenesis.
AB  - The interaction between CD40 and its cognate ligand, CD40 ligand, is a primary
      regulator of the peripheral immune response, including modulation of T lymphocyte
      activation, B lymphocyte differentiation and antibody secretion, and innate
      immune cell activation, maturation, and survival. Recently, we and others have
      identified CD40 expression on a variety of CNS cells, including endothelial
      cells, smooth muscle cells, astroglia and microglia, and have found that, on many
      of these cells, CD40 expression is enhanced by pro-inflammatory stimuli.
      Importantly, the CD40-CD40 ligand interaction on microglia triggers a series of
      intracellular signaling events that are discussed, beginning with Src-family
      kinase activation and culminating in microglial activation as evidenced by tumor
      necrosis factor-alpha secretion. Based on the involvement of microglial
      activation and brain inflammation in Alzheimer's disease pathogenesis, we have
      investigated co-stimulation of microglia, smooth muscle, and endothelial cells
      with CD40 ligand in the presence of low doses of freshly solubilized amyloid-beta
      peptides. Data reviewed herein show that CD40 ligand and amyloid-beta act
      synergistically to promote pro-inflammatory responses by these cells, including
      secretion of interleukin-1 beta by endothelial cells and tumor necrosis factor
      alpha by microglia. As these cytokines have been implicated in neuronal injury, a
      comprehensive model of pro-inflammatory CD40 ligand and amyloid-beta initiated
      Alzheimer's disease pathogenesis (mediated by multiple CNS cells) is proposed.

PMID- 11578773
TI  - Immunological aspects of microglia: relevance to Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive dementing neurologic illness, and the
      most frequent cause of dementia in the elderly. Neuritic plaques are one of the
      main neuropathological findings in AD, and the major protein component is the
      beta-amyloid protein (A beta). Another striking feature of neuritic plaques is
      the presence of activated microglia, cytokines, and complement components,
      suggestive of "inflammatory foci" within AD brain. In this review, we will
      examine the mechanisms by which microglia become activated in AD, emphasizing the
      role in the A beta protein and proinflammatory cytokines. As well, pathways for
      suppression of microglial activation by immunosuppressive cytokines will be
      described. Inflammation mediated by activated microglia is an important component
      of AD pathophysiology, and strategies to control this response could provide new
      therapeutic approaches for the treatment of AD.

PMID- 11578774
TI  - Functional role of TGF beta in Alzheimer's disease microvascular injury: lessons
      from transgenic mice.
AB  - Recent studies have implicated pro- and anti-inflammatory cytokines as integral
      to Alzheimer's disease (AD) pathogenesis. Among them, transforming growth factor
      beta (TGF-beta) is emerging as an important factor in regulating inflammatory
      responses. This multifunctional cytokine might be centrally involved in several
      aspects of AD pathogenesis by regulating beta-amyloid precursor protein synthesis
      and processing, plaque formation, astroglial and microglial response and neuronal
      cell death. Among all of these potential roles, studies in transgenic and
      infusion animal models have shown that TGF-beta may primarily contribute to AD
      pathogenesis by influencing A beta production and deposition, which in turn might
      result in damage to the brain microvasculature. The lessons learned from these
      models are of great interest not only for understanding of the role of TGF-beta
      in AD, but also for future treatments where testing of anti-inflammatory agents
      such as ibuprofen and an amyloid vaccine hold great promise. In this regard,
      further elucidation of the signal pathways by which TGF-beta exerts its effect in
      AD might lead to specific targets for further therapeutic intervention.

PMID- 11578775
TI  - S100B proteins that lack one or both cysteine residues can induce inflammatory
      responses in astrocytes and microglia.
AB  - The astrocytic protein S100B stimulates neurite outgrowth and neuronal survival
      during CNS development. S100B can also stimulate glial activation, leading to
      induction of pro-inflammatory molecules like interleukin-1 beta (IL-1 beta) and
      inducible nitric oxide synthase (iNOS). Although it is known that S100B's
      neurotrophic activity requires a disulfide-linked dimeric form of the protein,
      the structural features of S100B that are important for glial activation have not
      been defined. As an initial step towards understanding the structural features of
      S100B required for its action on glia and to determine if these features are
      different from those required for its action on neurons, we tested two mutants of
      S100B for their ability to activate glia. The C68VC84S mutant lacks S100B's two
      cysteine residues (cys68, cys84) and lacks neurotrophic activity (Winningham
      Major et al., 1989, J. Cell Biol. 109 3063-3071), and the truncation mutant
      S100B83stop lacks the C-terminal nine residues (including cys84) that have been
      shown to be important for some S100B:target protein interactions. We report here
      that both C68VC84S and S100B83stop stimulate glial activation, as determined by
      induction of iNOS and IL-1 beta in rat primary astrocyte and microglial cultures.
      C68VC84S showed activation profiles similar to those of wild-type S100B,
      demonstrating that a disulfide-linked dimer is not required for glial activation.
      S100B83stop also stimulated both iNOS and IL-1 beta, although S100B83stop was
      significantly less effective than wild-type S100B in inducing iNOS. These results
      indicate that the C-terminal region of S100B is not required for glial
      activation; however, its presence may influence the degree of activation by the
      protein. Altogether, these studies demonstrate that the structural features
      required for S100B's neurotrophic activity are distinct from those affecting its
      glial activation activity.

PMID- 11578776
TI  - Cerebrospinal fluid S100B is elevated in the earlier stages of Alzheimer's
      disease.
AB  - Postmortem demonstration of increased expression of biologically active S100B in
      Alzheimer's disease (AD) and its relation to progression of neuropathological
      changes across the cortical regions suggests involvement of this astrocytic
      cytokine in the pathophysiology of AD. The hypothesis that the overexpression of
      S100B in Alzheimer brain is related to the progression of clinical symptoms was
      addressed in living persons by measuring S100B concentrations in cerebrospinal
      fluid (CSF) from AD patients with a broad range of clinical dementia severity and
      from healthy older persons. The effect of normal aging on CSF S100B
      concentrations also was estimated. CSF S100B did not differ between all 68 AD
      subjects (0.98+/-0.09 ng/ml (mean+/-S.E.M.)) and 25 healthy older subjects
      (0.81+/-0.13 ng/ml). When AD subjects were divided into mild/moderate stage and
      advanced stage clinical dementia severity by the established Clinical Dementia
      Rating Scale (CDR) criteria, S100B was significantly higher in the 46
      mild/moderate stage AD subjects (1.17+/-0.11 ng/ml) than in either the 22
      advanced stage AD subjects (0.60+/-0.12 ng/ml) or the healthy older subjects.
      Consistent with higher CSF S100B in mild to moderate AD, there was a significant
      correlation among all AD subjects between CSF S100B and cognitive status as
      measured by the Mini Mental State Exam (MMSE) score. CSF S100B did not differ
      between healthy older subjects and healthy young subjects. These results suggest
      increased CNS expression of S100B in the earlier stages of AD, and are consistent
      with a role for S100B in the initiation and/or facilitation of neuritic plaque
      formation in AD brain.

PMID- 11578778
TI  - Apolipoprotein E and apolipoprotein E receptors modulate A beta-induced glial
      neuroinflammatory responses.
AB  - Large numbers of activated glia are a common pathological feature of many
      neurodegenerative disorders, including Alzheimer's disease (AD). Several
      different stimuli, including lipopolysaccharide (LPS), dibutyryl (db)cAMP, and
      aged amyloid-beta 1-42 (A beta), can induce glial activation in vitro, as
      measured by morphological changes and the production of pro-inflammatory
      cytokines and oxidative stress molecules. Only A beta-induced activation is
      attenuated by the addition of exogenous apolipoprotein E (apoE)-containing
      particles. In addition, only A beta also induces an increase in the amount of
      endogenous apoE, the primary apolipoprotein expressed by astrocytes in the brain.
      The functional significance of the increase in apoE appears to be to limit the
      inflammatory response. Indeed, compared to wild type mice, glial cells cultured
      from apoE knockout mice exhibit an enhanced production of several pro
      inflammatory markers in response to treatment with A beta and other activating
      stimuli. The mechanism for both the A beta-induced glial activation and the
      increase in apoE appears to involve apoE receptors, a variety of which are
      expressed by both neurons and glia. Experiments using receptor associated protein
      (RAP), an inhibitor of apoE receptors with a differential affinity for the low
      density lipoprotein receptor (LDLR) and the LDLR-related protein (LRP), revealed
      that LRP mediates A beta-induced glial activation, while LDLR mediates the A beta
      induced changes in apoE levels. In summary, both an apoE receptor agonist (apoE)
      and an antagonist (RAP) inhibit A beta-induced glial cell activation. Thus, apoE
      receptors appear to translate the presence of extracellular A beta into cellular
      responses, both initiating glial cell activation and limiting its scope by
      inducing apoE, an anti-inflammatory agent.

PMID- 11578777
TI  - Purification and characterization of astrocyte-secreted apolipoprotein E and J
      containing lipoproteins from wild-type and human apoE transgenic mice.
AB  - The varepsilon4 allele of apolipoprotein E (apoE) is a genetic risk factor for
      Alzheimer's disease (AD). In order to gain a better understanding of the
      molecular mechanisms by which apoE and possibly other apolipoproteins produced in
      the central nervous system (CNS) influence AD pathogenesis, we have purified and
      characterized the two most abundant apolipoproteins produced in the CNS, apoE and
      apoJ. We purified apoE and apoJ from primary cultures of mouse astrocytes, which
      were derived from transgenic mice expressing human apoE isoforms in the absence
      of mouse apoE. Utilizing antibody affinity columns, we were able to purify both
      human apoE3 and apoE4, as well as mouse apoJ-containing lipoproteins. Astrocyte
      secreted human apoE was present in high density-like lipoproteins of three
      predominant sizes ranging from 8 to 15 nm in diameter. Mouse apoJ was in
      particles between 10 and 17 nm in diameter with a peak size range of
      approximately 11 nm. ApoE and apoJ were in distinct lipoproteins. Utilization of
      quick-freeze, deep-etch electron microscopy revealed the apoE particles were
      discs while the apoJ particles were smaller and more irregular in appearance. The
      lipid composition of apoE particles was very different from those containing
      apoJ. ApoE-particles contained a similar mass of apoE and lipid, with cholesterol
      and phospholipid being about equal in mass per particle. ApoJ-particles were
      relatively lipid poor (three parts protein, one part lipid), with phospholipids
      being much more abundant than cholesterol. Detailed characterization of
      phospholipid composition by electrospray ionization mass spectrometry analysis
      revealed ethanolamine glycerophospholipids to be the most abundant phospholipid
      present in both apoE and apoJ particles. Analysis of cerebrospinal fluid from
      apoE3 and apoE4 transgenic mice revealed that human and mouse apoE were in
      particles the same size as those secreted by astrocytes. Further use of
      physiological preparations of CNS-derived lipoproteins may allow for a detailed
      understanding of the role of these molecules in the normal brain and in diseases
      such as AD.

PMID- 11578779
TI  - Estrogen (E2) and glucocorticoid (Gc) effects on microglia and A beta clearance
      in vitro and in vivo.
AB  - The accumulation of fibrillar aggregates of beta Amyloid (A beta) in Alzheimer's
      Disease (AD) brain is associated with chronic brain inflammation. Although
      activated microglia (mu glia) can potentially clear toxic amyloid, chronic
      activation may lead to excessive production of neurotoxins. Recent
      epidemiological and clinical data have raised questions about the use of anti
      inflammatory steroids (glucocorticoids, Gcs) and estrogens for treatment or
      prevention of AD. Since very little is known about steroid effects on mu glial
      interactions with amyloid, we investigated the effects of the synthetic Gc
      dexamethasone (DXM) and 17-beta estradiol (E2) in vitro in a murine mu glial-like
      N9 cell line on toxin production and intracellular A beta accumulation. To
      determine whether the steroid alterations of A beta uptake in vitro had relevance
      in vivo, we examined the effects of these steroids on A beta accumulation and mu
      glial responses to A beta infused into rat brain. Our in vitro data demonstrate
      for the first time that Gc dose-dependently enhanced mu glial A beta accumulation
      and support previous work showing that E2 enhances A beta uptake. Despite both
      steroids enhancing uptake, degradation was impeded, particularly with Gcs.
      Distinct differences between the two steroids were observed in their effect on
      toxin production and cell viability. Gc dose-dependently increased toxicity and
      potentiated A beta induction of nitric oxide, while E2 promoted cell viability
      and inhibited A beta induction of nitric oxide. The steroid enhancement of mu
      glial uptake and impedence of degradation observed in vitro were consistent with
      observations from in vivo studies. In the brains of A beta-infused rats, the mu
      glial staining in entorhinal cortex layer 3, not associated with A beta deposits
      was increased in response to A beta infusion and this effect was blocked by
      feeding rats prednisolone. In contrast, E2 enhanced mu glial staining in A beta
      infused rats. A beta-immunoreactive (ir) deposits were quantitatively smaller,
      appeared denser, and were associated with robust mu glial responses. Despite the
      fact that steroid produced a smaller more focal deposit, total extracted A beta
      in cortical homogenate was elevated. Together, the in vivo and in vitro data
      support a role for steroids in plaque compaction. Our data are also consistent
      with the hypothesis that although E2 is less potent than Gc in impeding A beta
      degradation, long term exposure to both steroids could reduce A beta clearance
      and clinical utility. These data showing Gc potentiation of A beta-induced mu
      glial toxins may help explain the lack of epidemiological correlation for AD. The
      failure of both steroids to accelerate A beta degradation may explain their lack
      of efficacy for treatment of AD.

PMID- 11578780
TI  - Regulation of beta-amyloid stimulated proinflammatory responses by peroxisome
      proliferator-activated receptor alpha.
AB  - Amyloid deposition within the brains of Alzheimer's Disease patients results in
      the activation of microglial cells and the induction of a local inflammatory
      response. The interaction of microglia or monocytes with beta-amyloid (A beta)
      fibrils elicits the activation a complex tyrosine kinase-based signal
      transduction cascade leading to stimulation of multiple independent signaling
      pathways and ultimately to changes in proinflammatory gene expression. The A beta
      stimulated expression of proinflammatory genes in myeloid lineage cells is
      antagonized by the action of a family of ligand-activated nuclear hormone
      receptors, the peroxisome proliferator-activated receptors (PPARs). We report
      that THP-1 monocytes express predominantly PPAR gamma isoform and lower levels of
      PPAR alpha and PPAR delta isoforms. PPAR mRNA levels are not affected by
      differentiation of the cells into a macrophage phenotype, nor are they altered
      following exposure to the classical immune stimulus, lipopolysaccharide. Previous
      studies have found that PPAR gamma agonists act broadly to inhibit inflammatory
      responses. The present study explored the action of the PPAR alpha isoform and
      found that PPAR alpha agonists inhibited the A beta-stimulated expression of
      TNFalpha and IL-6 reporter genes in a dose-dependent manner. Moreover, the PPAR
      alpha agonist WY14643 inhibited macrophage differentiation and COX-2 gene
      expression. However, the PPAR alpha agonists failed to inhibit A beta-stimulated
      elaboration of neurotoxic factors by THP-1 cells. These findings demonstrate that
      PPAR alpha acts to suppress a diverse array of inflammatory responses in
      monocytes.

PMID- 11578781
TI  - Ligand modulation of glial activation: cell permeable, small molecule inhibitors
      of serine-threonine protein kinases can block induction of interleukin 1 beta and
      nitric oxide synthase II.
AB  - Activated glia (astrocytes and microglia) and their associated neuroinflammatory
      sequelae have been linked to the disease progression of several neurodegenerative
      disorders, including Alzheimer's disease. We found that the experimental anti
      inflammatory drug K252a, an inhibitor of calmodulin regulated protein kinases
      (CaMKs), can block induction of both the oxidative stress related enzyme iNOS and
      the proinflammatory cytokine IL-1 beta in primary cortical glial cultures and the
      microglial BV-2 cell line. We also found that the profile of CaMKIV and CaMKII
      isoforms in primary cortical glial cultures and BV-2 cells is distinct from that
      found in neurons. Knowledge of cellular mechanisms and high throughput screens of
      a pharmacologically focused chemical library allowed the discovery of novel
      pyridazine-based compounds that are cell permeable ligand modulators of gene
      regulating protein kinases involved in the induction of iNOS and IL-1 beta in
      activated glia. Pyridazine-based compounds are attractive for the development of
      new therapeutics due to the retention of the remarkable pharmacological
      properties of K252a and related indolocarbazole alkaloids, and presence of
      enhanced functional selectivity in a comparatively simple structure amenable to
      diverse synthetic chemistries.

PMID- 11578782
TI  - Pathological glial tau accumulations in neurodegenerative disease: review and
      case report.
AB  - Abnormal deposits of tau protein accumulate in glia in many neurodegenerative
      diseases. This suggests that in some instances the disease process may target
      glial tau, with neuronal degeneration a secondary consequence of this process. In
      this report, we summarize the pattern of glial tau pathology in various
      neurodegenerative disorders and add original findings from a case of sporadic
      frontotemporal dementia that exhibits astrocytic tau pathology. The
      neurodegenerative diseases span the spectrum of relative neuronal and glial tau
      involvement, from disorders affecting only neuronal tau to those in which
      abnormal tau deposits are found only in glia. From this, we conclude that glial
      tau can be a primary target of the disease process, and that this can lead to
      neuronal degeneration.

PMID- 11578784
TI  - Comparison of the two-sided single triangular test to the double triangular test.
AB  - Comparative clinical trials are designed to determine whether a new treatment has
      either superior or different efficacy than a standard, that is, if theta
      represents a measure of treatment difference, to test the null hypothesis H(0):
      theta = 0 against the alternative hypothesis H(1) of either superior (theta > 0,
      one-sided) or different (theta not equal 0, two-sided with H(1)(+): theta > 0 and
      H(-)(1): theta < 0) efficacy. The triangular test (TT), a group sequential
      method, allows for early stopping of such trials. Its one-sided version (single
      TT) and two-sided version (double TT) were implemented in the first release of
      PEST software. The third release of PEST proposed a modification of the single
      TT, allowing rejection of H(0) in favor of H(-)(1) when very early data show
      strong inferiority of the new treatment as compared with the standard. Thus, our
      aim was to compare this modified single TT, referred to as a two-sided test in
      PEST 3, with the double TT and two-sided single-stage design (SSD). The
      statistical properties of the SSD and double TT were perfectly similar under all
      hypotheses. The modified single TT was underpowered as compared to the two others
      (the probability of falsely accepting H(0) strictly under H(-)(1) was 0.65
      instead of 0.05), but the average sample number function was lower than the one
      of the double TT under all H(-)(1) hypotheses (-56% strictly under H(-)(1)). We
      conclude that the modified single TT offers a two-sided conclusion with many
      fewer patients than the double TT, but at the expense of a strong decrease in
      power under H(-)(1).

PMID- 11578783
TI  - Considerations in the evaluation of surrogate endpoints in clinical trials.
      summary of a National Institutes of Health workshop.
AB  - We report on recommendations from a National Institutes of Health Workshop on
      methods for evaluating the use of surrogate endpoints in clinical trials, which
      was attended by experts in biostatistics and clinical trials from a broad array
      of disease areas. Recent advances in biosciences and technology have increased
      the ability to understand, measure, and model biological mechanisms; appropriate
      application of these advances in clinical research settings requires
      collaboration of quantitative and laboratory scientists. Biomarkers, new examples
      of which arise rapidly from new technologies, are used frequently in such areas
      as early detection of disease and identification of patients most likely to
      benefit from new therapies. There is also scientific interest in exploring
      whether, and under what conditions, biomarkers may substitute for clinical
      endpoints of phase III trials, although workshop participants agreed that these
      considerations apply primarily to situations where trials using clinical
      endpoints are not feasible. Evaluating candidate biomarkers in the exploratory
      phases of drug development and investigating surrogate endpoints in confirmatory
      trials require the establishment of a statistical and inferential framework. As a
      first step, participants reviewed methods for investigating the degree to which
      biomarkers can explain or predict the effect of treatments on clinical endpoints
      measured in clinical trials. They also suggested new approaches appropriate in
      settings where biomarkers reflect only indirectly the important processes on the
      causal path to clinical disease and where biomarker measurement errors are of
      concern. Participants emphasized the need for further research on development of
      such models, whether they are empirical in nature or attempt to describe
      mechanisms in mathematical terms. Of special interest were meta-analytic models
      for combining information from multiple studies involving interventions for the
      same condition. Recommendations also included considerations for design and
      conduct of trials and for assemblage of databases needed for such research.
      Finally, there was a strong recommendation for increased training of quantitative
      scientists in biologic research as well as in statistical methods and modeling to
      ensure that there will be an adequate workforce to meet future research needs.

PMID- 11578785
TI  - Principles for enhanced recruitment of subjects in a large clinical trial. the
      XENDOS (XENical in the prevention of Diabetes in Obese Subjects) study
      experience.
AB  - In most clinical trials it is problematic to recruit enough patients within a
      reasonable time period. Prolonged or inefficient recruitment or both can have
      negative scientific and economic consequences. The XENDOS (XENical in the
      prevention of Diabetes in Obese Subjects) study is an ongoing randomized, double
      blind, placebo-controlled, prospective, multicenter trial investigating whether
      orlistat combined with hypocaloric diet and moderate physical exercise can reduce
      the incidence of diabetes in obese subjects. To implement the XENDOS protocol and
      recruit the study patients, we designed a system for centralized patient
      recruitment and centralized scheduling of patients and staff at the 22
      collaborating centers. The recruitment and inclusion phase was divided into a
      series of different consecutive examinations of increasing complexity. Relatively
      simple initial examinations enabling a large throughput of patients were followed
      by more detailed examinations of fewer subjects, by then known to fulfil some of
      the study-specific requirements. With the aid of object-oriented techniques, the
      software was modularized to enable concurrent engineering. We also selected a
      structure where plug-in modules handling specific tasks could be added to the
      system as needed. The design was supported by a flow-oriented view of the
      progress of the patients through the study. With this overall solution we managed
      to include 3305 subjects (98.8% of the requested number) within less than 4
      months. The sex distribution (44.8% men) and the number of patients with impaired
      glucose tolerance (IGT), (21.1%) were in close accordance with, or far better
      than, the requirements of the protocol (45% men, at least 10% IGT patients). The
      basic design of the XENDOS information system can be adapted to fulfil the
      requirements of other study protocols within the fields of obesity, diabetes,
      hypertension, coronary heart disease, etc. Shortening the recruitment and
      inclusion phase of large clinical trials is of great value both to be medical
      society and the pharmaceutical industry.

PMID- 11578786
TI  - Sociodemographic and clinical predictors of participation in two randomized
      trials: findings from the Collaborative Ocular Melanoma Study COMS report no. 7.
AB  - Collecting sociodemographic and clinical data concerning patients who choose not
      to enroll in a randomized clinical trial can be useful in assessing the
      feasibility of attaining sample size goals during the course of a trial. It can
      also aid in addressing the extent of generalizability of trial findings after a
      trial has ended. The Collaborative Ocular Melanoma Study (COMS) consists of two
      multicenter randomized clinical trials to evaluate the effectiveness of
      radiotherapy in comparison to standard enucleation (removal of the affected eye)
      in prolonging survival of patients with choroidal melanoma. One trial is for
      patients with large tumors and the other trial is for patients with medium-sized
      tumors. The same baseline sociodemographic and clinical data were collected for
      both enrolled patients and eligible patients who did not enroll in the randomized
      trials during the first 3 years of patient recruitment. Partial information on
      nonrandomized patients was collected thereafter. Recruitment ended in the large
      tumor and medium tumor trials on December 31, 1994, and July 31, 1998,
      respectively. From November 1986 through July 1998, 6906 patients with choroidal
      melanoma were evaluated for the randomized trials, of whom 4191 (61%) were
      eligible for enrollment. Logistic regression methods were used to identify
      factors predictive of trial participation. Sociodemographic factors that appeared
      to be associated (p < 0.15) with participation in the univariable models in the
      medium tumor trial were age 60 years or older, less than college education,
      nonmanagerial occupation, current smoking, and residing in the same state as a
      COMS clinical center. In the large tumor trial, males, individuals who were not
      college-educated, and individuals residing in the same state as a COMS clinical
      center were more likely to enroll. In both trials, clinical determinants of
      participation were larger tumor dimensions and initial visual acuity worse than
      20/20 in the study eye. In multivariable regression models, the variables that
      were significantly predictive of enrollment (p < 0.05) in at least one of the
      trials were older age, residence in the same state, larger tumor basal diameter,
      and worse initial visual acuity in the study eye. Knowledge of possible
      sociodemographic and clinical predictors of differentials in patient
      participation for nonenrolled patients may help to refine patient education and
      recruitment strategies for future trials. Patient enrollment in clinical trials
      may be increased by heightened physician awareness of such predictors, strategies
      for addressing these differences, and enhanced communication between physicians
      and patients.

PMID- 11578787
TI  - Individual patient-versus literature-based meta-analysis of survival data: time
      to event and event rate at a particular time can make a difference, an example
      based on head and neck cancer.
AB  - The objective of this study is to compare the results of an individual patient
      based and a literature-based meta-analysis in chemotherapy in head and neck
      cancer and to identify the sources of difference. For all head and neck cancer
      randomized controlled clinical trials comparing chemotherapy and loco-regional
      treatment with loco-regional treatment alone, both the literature data and the
      individual patient data are retrieved and meta-analyses performed and compared.
      Only survival data are used as outcome, although both time to death and mortality
      at specific time points are considered in different analyses. There are
      substantial differences between the individual patient-based and the literature
      based meta-analyses. The most important reason for the differing results is that
      the individual patient-based meta-analysis is based on a time to event analysis,
      whereas the literature-based meta-analysis is based on mortality at a specific
      time point. Mortality can change substantially with follow-up time. The absolute
      survival differences in the case study, for instance, increase from 2.6% at 2
      years to 5.6% at 5 years.

PMID- 11578788
TI  - Rationale and design of the St. Francis Heart Study: a randomized clinical trial
      of atorvastatin plus antioxidants in asymptomatic persons with elevated coronary
      calcification.
AB  - Early detection of asymptomatic subjects who are at risk for future
      cardiovascular events may allow for earlier medical treatment in order to prevent
      disease progression and future events. Electron-beam computed tomography
      accurately identifies people with increased coronary calcification, which is
      correlated with increased coronary plaque mass, increased likelihood of
      obstructive coronary disease, and increased likelihood of future cardiovascular
      events. The St. Francis Heart Study is a single-center combination study of men
      and women 50-70 years old that includes a natural history study of the relation
      between calcium scores and cardiovascular events (n = 5582), the association of
      calcium scores with traditional and nontraditional coronary disease risk factors
      (n = 1160), and a randomized clinical trial designed to assess the benefit of
      combination treatment with atorvastatin, vitamin C, and vitamin E, as compared to
      placebos, in subjects with elevated age- and gender-adjusted coronary
      calcification (n = 1007). Mean follow-up duration will be 4 years. The study is
      proceeding on schedule with anticipated completion by August 2002. It should
      provide important information regarding the benefits of treating asymptomatic men
      and women who have elevated coronary artery calcium, using cholesterol reduction
      and antioxidant therapy. The article describes the design of the St. Francis
      Heart Study.

PMID- 11578789
TI  - The Correction of Myopia Evaluation Trial (COMET): design and general baseline
      characteristics.
AB  - The Correction of Myopia Evaluation Trial (COMET) is a multicenter, randomized,
      double-masked, controlled clinical trial evaluating whether there is a difference
      in the progression of myopia between children wearing progressive addition lenses
      (PALs) versus conventional single vision lenses (SVLs), as measured by
      cycloplegic autorefraction. Axial length, measured by A-scan ultrasonography, is
      an additional outcome measure. To meet the recruitment goal of 450 participants,
      eligible children ages 6-11 years (inclusive) with myopia in both eyes (spherical
      equivalent between -1.25 diopters (D) and -4.50 D, astigmatism < or = 1.50 D, and
      anisometropia < 1.00 D) were recruited at four clinical centers between September
      1997 and September 1998. Children who participated were assigned to receive PALs
      (Varilux Comfort with a +2.00 D addition) or SVLs. Measures include standardized
      cycloplegic autorefraction (Nidek ARK700A autorefractor), axial length (Sonomed
      A2500 ultrasound), subjective refraction (Marco TRS system), visual acuity
      (modified Early Treatment Diabetic Retinopathy Study protocol), accommodation
      (Canon R-1), and phoria (cover test and Maddox rod). Outcome measures are
      collected annually; adherence is assessed and prescriptions updated semiannually.
      Participants are being followed for at least 3 years. COMET enrolled 469
      children. Their mean age is 9.3 years (range 6-11 years); 52% are female. COMET
      children are ethnically diverse, according to a self-report with 46% White, 26%
      African American, 14% Hispanic, and 8% Asian. Best-corrected visual acuity is
      better than 20/32 in both eyes. Baseline mean (+/-SD) cycloplegic refractive
      correction is -2.38 D (+/-0.81) in the right eye and -2.40 D (+/-0.82) in the
      left eye; mean (+/-SD) axial length is 24.1 mm (+/-0.7) in both eyes. Follow-up
      of these children will provide a first step in answering the important question
      of whether there are effective means to slow myopia progression. Study results
      should be applicable to a large proportion of children with myopia. The study
      will also provide useful information on myopia progression in children wearing
      conventional single vision lenses.

PMID- 11578790
TI  - The application of a Dutch consensus diagnostic strategy for pulmonary embolism
      in clinical practice.
AB  - In The Netherlands, the 'Dutch consensus strategy' was formulated in 1993 as a
      diagnostic strategy for patients with suspected pulmonary embolism. Four years
      after its introduction, the application of this strategy was investigated. A
      questionnaire was sent to the hospital management and the departments of internal
      medicine and pulmonology of all Dutch hospitals. In total, 384 questionnaires
      were sent out. The response rates of the internists and pulmonologists were 63
      and 65%, respectively. The specialists reported to have followed the consensus
      strategy in 75% of the patients seen the month prior to the questionnaire.
      However, analysis of only the last patient with the suspicion of pulmonary
      embolism revealed that the consensus strategy was followed in 55 of the 162
      patients. As well, an overuse and an underuse of the different diagnostic
      facilities was documented. Furthermore almost a quarter of the patients were
      treated without an ascertained diagnosis, whereas 11% were not treated despite an
      improper exclusion of venous thrombo-embolism. Compared to a survey in 1994, the
      use of the 'Dutch consensus strategy' has not improved dramatically. In 34% of
      the patients, the consensus strategy was strictly followed (i.e. without any
      additional investigation); however in 67% of the patients a proper diagnosis was
      achieved. In any diagnostic strategy, two aspects should be considered. First the
      availability of the different facilities. Second the acceptance of the strategy
      by the physicians, involved in the diagnosis of patients with clinically
      suspected pulmonary embolism.

PMID- 11578792
TI  - Detection of Mycobacterium tuberculosis complex DNA in pericardial fluid, bone
      marrow and peripheral blood in a patient with pericardial tuberculosis. A case
      report.
AB  - Definitive diagnosis of tuberculous pericarditis requires identification of
      bacilli in pericardial fluid or tissue. Conventional diagnostic methods are time
      consuming and have a low sensitivity making bacteriological confirmation of the
      disease very difficult. Hereby, we report the case of molecular detection of
      Mycobacterium tuberculosis in pericardial fluid, bone marrow and peripheral blood
      from a 63-year-old woman with pericardial tuberculosis, using a nested PCR assay
      specific for IS6110 insertion element of M. tuberculosis complex. The patient had
      an excellent response to a three-drug combination anti-tuberculous regimen and 1
      year later was asymptomatic, without evidence of constrictive pericarditis.

PMID- 11578791
TI  - Pseudoparasitic pneumonia after bone marrow transplantation.
AB  - We present a female patient from Somalia with an acute lymphoblastic leukemia,
      who received an allogeneic bone marrow transplantation (BMT) and developed
      several periods of moderate to severe pulmonary symptoms that were accompanied by
      pulmonary infiltrates and peripheral blood eosinophilia. After several
      recurrences an open lung biopsy was performed, which initially gave rise to the
      diagnosis parasitic infection. Later on this diagnosis was questioned and it was
      suggested that the structures were artifacts that might have been aspirated.
      Nevertheless, after the immediately given antihelminthic treatment no peripheral
      blood eosinophilia occurred anymore, but at that point of time pulmonary function
      was already severely hampered and eventually led to a lethal complication. With
      the worldwide increasing migration from Third World countries with a high
      prevalence of parasitic infections, more patients will receive immunosuppressive
      therapies in countries less familiar with parasites. This may complicate
      diagnostic procedures, prevent early recognition and delay adequate treatment.
      Specific screening for opportunistic parasitic infections of the population at
      risk before BMT and a great awareness for these infections is strongly
      recommended.

PMID- 11578793
TI  - Lemierre's syndrome. Sepsis complicating an anaerobic oropharyngeal infection.
AB  - Previously healthy people without interfering conditions are rarely affected by
      anaerobic infections. We report a young patient with extended septic emboli in
      the lungs, after an episode of sore throat, due to anaerobic bacteremia with
      Fusobacterium necrophorum. The first description of oropharyngeal infection
      complicated by sepsis was given by Lemierre in 1936. Knowledge of Lemierre's
      syndrome should lead to early recognition and prompt action against this sporadic
      and possible fatal illness.

PMID- 11578794
TI  - Genetic and metabolic factors predicting risk of cardiovascular disease in
      familial hypercholesterolemia.
AB  - Familial hypercholesterolemia is a hereditary metabolic disorder characterised by
      high low-density lipoprotein cholesterol levels and an extreme risk of premature
      cardiovascular disease. In patients with heterozygous familial
      hypercholesterolemia a substantial variation is seen in both the severity of the
      hypercholesterolemia and onset of atherosclerotic disease symptoms. We discuss
      the contribution of additional atherogenic risk factors of metabolic,
      environmental and genetic origin. Subclinical disease measurements, such as the
      intima media thickness (IMT), assessed by ultrasonography, may contribute to a
      better risk prediction of future cardiovascular disease in these patients.

PMID- 11578795
TI  - The (ir)relevance of plasma protein binding of anticancer drugs.
AB  - The major purpose of therapeutic drug monitoring is to enable drug dosage
      individualization for differences among patients in rates of drug metabolism
      and/or excretion. The standard analytical methods for measuring concentrations of
      drugs in plasma determine drug bound to plasma proteins as well as free drug
      dissolved in plasma water. For this reason, the relationship between total drug
      concentration in plasma and treatment outcome (i.e. toxicity and efficacy) will
      only be good if the degree of plasma protein binding of the agent is constant, or
      if so little drug is protein bound that changes in binding make insignificant
      changes in unbound concentration. A review of available literature data indicates
      that, in general, protein binding of anticancer drugs is not of principal
      clinical relevance. However, there are several instances, in which monitoring of
      unbound concentrations might be useful: (i) agents demonstrating protein
      concentration-dependent binding, (ii) agents that bind irreversible or near
      covalently, (iii) when formulation excipients modulate unbound drug levels, and
      (iv) metabolically interconvertible agents. While available evidence suggests
      that for these agents unbound drug levels correlate better with clinical effects
      than total plasma concentrations, there are insufficient data to justify the
      recommendation of the routine use of unbound drug concentration monitoring for
      any of these agents at present.

PMID- 11578796
TI  - Effect of taurine on toxicity of cadmium in rats.
AB  - A study was undertaken to investigate the effect of taurine on the toxicity of
      cadmium in male Wistar rats. The rats were divided into six groups and fed
      different diets with or without supplement of 5% taurine and 150-300 ppm cadmium
      for 2 months. It was found that the body weight of rats, the ratios of liver and
      kidney weight to body weight, and the level of glutathione in the liver were
      decreased with increasing the dose of cadmium. The levels of cadmium in the liver
      and kidney, the levels of thiobarbituric acid-relative substances (TBARS) in the
      plasma and liver, the activities of aspartate transaminase (AST) and alanine
      transaminase (ALT) in the plasma, and the levels of blood urea nitrogen (BUN) and
      creatinine in the plasma of rats were increased with the increasing dose of
      cadmium. Hence, symptoms of cadmium toxicity in rats included loss of body
      weight, hepatotoxicity and nephrotoxicity. However, these toxic effects of
      cadmium were significantly reduced when the rats fed diet with supplement of
      taurine. Furthermore, the level of cadmium in the feces of rats treated with
      taurine and cadmium was higher than that of rats treated with cadmium alone. It
      indicated that taurine might play a role in reducing the toxic effect of cadmium
      in rats.

PMID- 11578797
TI  - Effects of maternal age on teratogenicity of di-n-butyltin diacetate in rats.
AB  - The present study was designed to assess changes in the teratogenic potency of di
      n-butyltin diacetate (DBTA) with increasing maternal age in rats. Pregnant Wistar
      rats of 3, 7.5 or 12 months were treated orally with DBTA at 0, 7.5, 10, 15 or 22
      mg/kg on day 8 of gestation. Cesarean sections were performed on day 20 of
      gestation. Maternal age had greater impact on litter size in the 7.5- and 12
      month dams than the 3-month dams. The death of most of the fetuses of the 12
      month dams made it difficult to evaluate the teratogenic potency of DBTA. In 3
      month groups, fetuses with external malformation, such as cleft mandible, cleft
      lower lip, ankyloglossia and/or schistoglossia, which are malformations typical
      of DBTA, were observed at 15 and 22 mg/kg, while similar malformations were
      observed in 7.5-month groups at doses of 10 mg/kg and above. At 15 and 22 mg/kg,
      the incidences of these malformations in 7.5-month groups were similar to these
      from 3-month groups. In our previous studies, however, single DBTA-treatment at
      10 mg/kg on day 8 of gestation has not produced such malformations from 3-month
      dams. The results suggest that the teratogenic potency of DBTA in 7.5-month dams
      may be greater than in 3-month dams.

PMID- 11578798
TI  - In vivo genotoxic effects of mercuric chloride in rat peripheral blood leucocytes
      using comet assay.
AB  - DNA damage induced by Mercuric chloride (HgCl2) in leucocytes of Wistar albino
      male rats has been studied in vivo. The comet assay or the alkaline single cell
      gel electrophoresis (SCGE) assay was used to measure the DNA damage. The rats
      were administered orally with doses ranging from 0.0054, 0.0108, 0.0216, 0.0432
      to 0.0864 mg/kg body weight (b.wt.) of HgCl2. The assay was performed on whole
      blood at 24, 48, 72 h, 1st and 2nd week. The reason leucocytes were used was to
      reflect biomarker studies in humans. A significant increase in mean comet tail
      length indicating DNA damage was observed at all time intervals with HgCl2 except
      in 2nd week post treatment when compared to controls. The mean comet tail length
      revealed a clear dose dependent increase from 0.0054 to 0.0432 mg/kg b.wt. A
      maximum increase in mean comet tail length was observed at 0.0432 mg/kg b.wt. 24
      h after treatment. From 48 h post treatment, the mean comet tail lengths of all
      the doses gradually decreased and by week 2 of post treatment, they had
      approached control levels, pointing to repair of the damaged DNA. These findings
      suggest that the comet assay is a highly sensitive technique to study DNA damage
      caused by metals.

PMID- 11578799
TI  - Nitric oxide and iron overload. Limitations of ESR detection by DETC.
AB  - The ability of the ESR technique based on diethyldithiocarbamate (DETC)
      administration was studied as a suitable method to assess NO generation in vivo.
      The technique was successfully employed to measure NO generation after LPS
      treatment. DETC2-Fe-NO adducts were detected in liver homogenates of iron
      overloaded animals. When iron was administered to the animals simultaneously with
      LPS, NO-dependent signal increased 122%, but the content of NO2- and NO3- in sera
      was significantly lower (44%) as compared to LPS-treated rats. Iron dextran
      administration was responsible for a three-fold increase in the DETC2-Fe-NO
      content in non-LPS treated rats, while NOS activity and sera NO2- and NO3- levels
      remained unaffected. The adduct generation rate by a chemical NO-source was
      recorded in the presence of either control or iron overloaded homogenates
      supplemented with DETC in vivo. The exposure of liver homogenates to NO was
      performed either by the addition of 1 mM SNAP as NO donor or infusing an aqueous
      NO solution. In the presence of iron overloaded samples the adduct generation
      rate was 3.8-4.4-fold higher than in the presence of control samples. This effect
      restricts the applicability of the method to experimental conditions where iron
      levels remain constant, therefore it is not suitable for NO generation studies in
      experimental models where animals were subjected to iron overload.

PMID- 11578800
TI  - Comparison of dose-responses of contact allergens using the guinea pig
      maximization test and the local lymph node assay.
AB  - The guinea pig maximization test (GPMT) has been used as a method for the
      prediction of skin sensitizing potential for over 30 years. Besides hazard
      identification, risk assessment of sensitizing chemicals requires the assessment
      of potency. For the determination of potency based on lowest effective dose
      levels, dose-response studies are required. In the standard GPMT a single
      concentration is used for intracutaneous and topical induction and the assay
      provides a qualitative assessment of allergenicity. This paper presents data
      derived from quantitative evaluation of the sensitizing potency of chemicals in
      the GPMT, based on multiple concentrations. We performed the GPMT in accordance
      with the original procedure of Magnusson and Kligman; and included in this
      procedure a range of intradermal and topical concentrations for induction. Three
      allergens with different sensitizing potencies, diethylamine (DEA), tetramethyl
      thiuram disulfide (TMTD) and zinc dimethyl dithiocarbamate (ZDMC) were tested.
      The data obtained with this test procedure were compared to data we previously
      obtained using the local lymph node assay (LLNA). Both the GPMT and the LLNA
      showed dose response relationships for the three chemicals tested. For the
      chemicals tested, both tests differed in the relative potencies based on
      benchmark concentrations. While both tests ranked DEA as the least potent
      allergen, the GPMT ranked ZDMC more potent than TMTD, the reverse being found in
      the LLNA. The nature of the data provided in the LLNA makes it likely that
      benchmarks as defined with this test are more reliable than that defined in the
      GPMT. However, further validation with human data is necessary.

PMID- 11578801
TI  - Characterization of antibody responses induced in rodents by exposure to food
      proteins: influence of route of exposure.
AB  - There is a growing interest in the development of methods to characterize the
      allergenic properties of novel proteins, particularly those expressed by
      transgenic crop plants. Approaches to the direct evaluation of allergenic
      potential have focused generally on the ability of proteins to induce antibody
      (particularly IgE antibody) after systemic (intraperitoneal; i.p.) or gavage
      administration to high IgE responder strain rodents. To date there has been no
      systematic comparison of the reliability, sensitivity or selectivity of these
      approaches. We have, therefore, compared antibody (IgG and IgE) responses induced
      in Brown Norway (BN) rats by daily gavage administration and in BALB/c strain
      mice following intraperitoneal or gavage exposure to food proteins of varying
      allergenic potential. Animals were exposed to the allergens peanut agglutinin and
      ovalbumin (OVA) or to a crude potato protein extract (PPE) containing acid
      phosphatase activity, a common foodstuff which appears to be of low
      allergenicity. All test proteins were clearly immunogenic when administered by
      gavage to BN rats, with measurable, and in some cases very vigorous, IgG antibody
      responses recorded for all animals. Identical exposure of BALB/c strain mice also
      stimulated detectable IgG antibody responses, with particularly high titers
      recorded following treatment with peanut agglutinin and somewhat less vigorous
      responses induced by OVA and PPE. Despite these high titer IgG antibody
      responses, however, none of the proteins provoked detectable IgE antibody
      following gavage administration to BN rats. In contrast, in BALB/c mice oral
      exposure to peanut agglutinin elicited high titer IgE antibody, although IgE
      antibody responses to both OVA and PPE were much weaker. Parenteral (i.p.)
      treatment of BALB/c strain mice with each of the test materials induced
      relatively high titer IgG antibody and a differential potential to stimulate IgE
      antibody was observed. High titer IgE responses were provoked by i.p.
      administration of peanut agglutinin and OVA, whereas PPE stimulated little or no
      detectable IgE antibody. It would appear, therefore, that while it is possible to
      elicit robust IgE responses by gavage exposure of BALB/c strain mice to some
      protein allergens, such as peanut agglutinin, such responses are generally weaker
      and less consistent than those provoked by i.p. administration. Furthermore,
      gavage treatment failed to induce detectable IgE responses in the BN rat,
      suggesting that the ability these animals to mount IgE responses is somewhat
      variable. Following i.p. administration to BALB/c strain mice, these proteins
      displayed immunological properties consistent with what is known of their
      allergenic potential in humans, suggesting that, following further evaluation
      with a wider range of proteins, this method may provide one approach to the
      identification of potential protein allergens.

PMID- 11578802
TI  - The role of hedgehog signalling in tumorigenesis.
AB  - It has long been known from work in both Drosophila and vertebrate systems that
      the hedgehog signalling pathway is pivotal to embryonic development, but the past
      5 years has seen an increase in our understanding of how members of this pathway
      are crucial to the processes of tumorigenesis. This important link was firmly
      established with the discovery that mutations in the gene encoding the hedgehog
      receptor molecule patched are responsible for both familial and sporadic forms of
      basal cell carcinoma (BCC), as well as a number of other tumour types. It is now
      known that a number of key members of the hedgehog cascade are involved in
      tumorigenesis, and dysregulation of this pathway appears to be a key element in
      the aetiology of a range of tumours.

PMID- 11578803
TI  - Anti-tumor promoting effects of multiflorane-type triterpenoids and cytotoxic
      activity of karounidiol against human cancer cell lines.
AB  - Forty-nine multiflorane-type triterpenoids consisting of 11 compounds isolated
      from the seeds of Trichosanthes kirilowii (Cucurbitaceae) and 38 of their
      derivatives have been evaluated for their inhibitory effects on Epstein-Barr
      virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O
      tetradecanoylphorbol-13-acetate in Raji cells as a primary screening test for
      anti-tumor promoters. All of the compounds tested showed an inhibitory effect
      against EBV-EA activation, and among which 43 were revealed to possess remarkable
      activity with potencies either comparable to or stronger than that of
      glycyrrhetic acid, a known natural anti-tumor promoter. Their structure-activity
      relationship is discussed. Evaluation of the cytotoxic activity of karounidiol
      (27) against human cancer cell lines exhibited cytotoxicity especially against a
      human renal cancer.

PMID- 11578804
TI  - Inhibitory effect of epigallocatechin gallate on adhesion of murine melanoma
      cells to laminin.
AB  - We examined the effects of five kinds of green tea catechin on the adhesion of
      mouse melanoma B16 cells to laminin. (-)-Epigallocatechin gallate (EGCG) and (-)
      epicatechin gallate in the culture medium were found to inhibit the cell
      adhesion. The adhesion to laminin pre-treated with EGCG was also impaired.
      Affinity chromatography revealed the binding affinity between laminin and EGCG.
      These data suggest that the inhibitory effect of EGCG on adhesion of melanoma
      cells to laminin is included in the mechanism(s) of previously reported
      metastasis inhibition elicited by EGCG and green tea infusion.

PMID- 11578805
TI  - In vitro bioassays for anticancer drug screening: effects of cell concentration
      and other assay parameters on growth inhibitory activity.
AB  - In vitro growth inhibition assays were performed using human cancer cell lines at
      various concentrations with experimental anticancer drugs such as the
      cryptophycins and other cytotoxins. The effect of variations in assay parameters
      on the observed growth inhibition of these anticancer therapeutic agents was
      determined. The results demonstrated that the observed inhibitory activity of
      these compounds varied inversely with the cell concentrations used. The observed
      differences in activity between different cytotoxins were not necessarily
      proportionate. Thus, the relative activities of two toxins also varied with cell
      concentration. Furthermore, the sensitivity of these cell lines to the cytostatic
      purine analog, 6-mercaptopurine (used as a control), varied with cell
      concentration as well. The activity of this compound was dependent on the medium
      used for cell growth, yielding good activity in Eagle's minimum essential medium,
      but not in Ham's F-12 (Kaigin) medium. Moreover, growth inhibition by
      cryptophycin as well as 6-mercaptopurine was also dependent on the serum
      concentration in the medium. Finally, the sensitivity of the cancer cell lines to
      various organic solvents commonly used as drug vehicles for in vitro testing,
      such as ethanol, dimethylformamide, and dimethylsulfoxide, was likewise found to
      vary inversely with cell concentration.

PMID- 11578807
TI  - Distribution of HER2(V655) genotypes in breast cancer cases and controls in the
      United States.
AB  - The minor variant frequency of a HER2 polymorphism (HER2(V655)) has been
      determined for 471 United States women enrolled in a multiracial case-control
      study. Allelic frequencies varied significantly by race. Genotypic distributions
      showed no excess breast cancer risk associated with inheritance of HER2(V655)
      either as carriers (OR=1.2, 95% CI=0.8-1.9), heterozygotes (OR=1.2, 95% CI=0.8
      1.9), or homozygotes (OR=1.4, 95% CI=0.4-4.2). Nor was there a significant
      association when each racial group was considered separately. The current study
      suggests the HER2(V655) allele is not a breast cancer risk factor for Caucasians,
      African-Americans, or Latinas.

PMID- 11578806
TI  - Irradiation with ultrasound of low output intensity increased chemosensitivity of
      subcutaneous solid tumors to an anti-cancer agent.
AB  - Ultrasound is a possible mechanical method to deliver small molecules into target
      cells. In order to evaluate the therapeutic potentials provided by ultrasound
      irradiation, we compared anti-tumor effects of electroporation- and ultrasound
      mediated chemotherapy and efficacy of gene transfer by the two methods. Electric
      pulses (5 Hz, 100 V/cm, 8 square-wave/100 microsec) or ultrasound (1 MHz, 2
      W/cm(2), 5 min) was delivered to subcutaneous solid tumors of murine lymphoma
      after the tumor-bearing mice received an intraperitoneal injection of bleomycin
      (BLM) (2.5 mg) or intratumoral injection of plasmid DNA containing the luciferase
      reporter gene. Administration of BLM alone did not affect the subsequent tumor
      growth but additive treatment with ultrasound irradiation suppressed the growth
      to the same level as electroporation. The luciferase activity of the DNA-injected
      tumors showed that ultrasound irradiation achieved better transfection efficiency
      than plasmid DNA injection alone but the efficacy was not as great as that by
      electroporation. The low energy level of ultrasound that is currently used for a
      diagnostic purpose and physical therapy in clinical fields can thereby increase
      the in vivo chemosensitivity of treated tumors but further modifications are
      necessary to achieve better efficacy of the ultrasound-mediated gene transfer.

PMID- 11578808
TI  - Concentration of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) in urine
      and alkali-hydrolyzed urine after consumption of charbroiled beef.
AB  - Heterocyclic amines (HAs) and polycyclic aromatic hydrocarbons are carcinogenic
      products formed during the cooking of meat at moderate to high temperatures. We
      have previously shown that the urinary concentration of 1-hydroxypyrene
      glucuronide, a metabolite of pyrene, increased significantly in ten subjects who
      had ingested charbroiled ground beef. We now report the time course and
      interindividual variation of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
      (PhIP) concentration in the urine samples from these ten subjects. PhIP
      concentration was determined in both untreated and alkali-hydrolyzed urine to
      obtain estimates of the proportion of conjugated PhIP metabolites in each
      subject. PhIP was measured by gas chromatography-negative ion chemical ionization
      mass spectrometry after derivatization with pentafluorobenzyl bromide. Ten
      healthy non-smoking males consumed identical amounts of broiled beef on five
      consecutive days. The morning after the first day of broiled beef consumption,
      urinary concentration of PhIP increased 14-38 fold above mean pre-feed
      concentration of PhIP in individual alkali-hydrolyzed urine samples. Following
      cessation of broiled beef consumption, urinary PhIP concentration declined to
      near pre-feed levels within 48-72 hrs. The ratio of total alkali-labile PhIP
      metabolites to unmetabolized PhIP varied by about 2.7-fold among subjects,
      ranging from 18:1 to 48:1, suggesting that interindividual differences in PhIP
      metabolism occur and can be detected by this method. This study of urinary PhIP
      following ingestion of meat cooked by charbroiling, that contains both HAs and
      polycyclic aromatic hydrocarbons, extends previous studies of ingestion of pan
      fried meat that contains primarily HAs. The results indicate that significant
      amounts of PhIP are bioavailable from ingestion of charbroiled ground beef and
      that measurement of proportions of alkali-labile PhIP metabolites and parent PhIP
      in human urine may yield information on individual metabolism of ingested PhIP.

PMID- 11578809
TI  - Killing of lymphoblastic leukemia cells by nitric oxide and taxol: involvement of
      NF-kappaB activity.
AB  - Nitric oxide (NO) and taxol are cytotoxic towards leukemia and tumor cells and
      interfere with the transcription factor NF-kappaB activity. NO and taxol
      inhibited NF-kappaB activity and were cytotoxic to human and murine leukemia
      cells, but at a different magnitude (30% cell killing and 80% inhibition of NF
      kappaB). Sub-effective concentrations of SNAP and taxol synergized in killing L
      1210 cells but either alone or in combination completely inhibited NF-kappaB.
      Pyrrolidine dithiocarbamate (PDTC) was cytotoxic on its own and inhibited NF
      kappaB activity. It potentiated NO and taxol killing but again there was no
      direct relationship between inhibition of NF-kappaB and cell killing. Neither NO
      nor taxol cytotoxicity was related to the cytoskeleton. Our results show that NO,
      taxol and PDTC induced apoptosis and NF-kappaB inhibition in leukemic cells but
      their cytotoxicity either alone or in combination, does not seem to be dependent
      on the inhibition of NF-KB activity.

PMID- 11578810
TI  - A novel homozygous deletion at chromosomal band 6q27 in an ovarian cancer cell
      line delineates the position of a putative tumor suppressor gene.
AB  - Chromosomal band 6q27 is believed to contain a tumor suppressor gene important in
      the development of several cancer types, including ovarian cancer. However,
      repeated efforts to identify a tumor suppressor gene in this region have been
      unsuccessful. Because homozygous deletions have been useful in the positional
      cloning of a number of tumor suppressor genes, we initiated a systematic search
      for such deletions in ovarian cancer cell lines using 6q microsatellite markers.
      One of the cell lines, OV167, was found to contain an 80 kb homozygous deletion
      encompassing marker D6S193 at 6q27 but excluding nearby marker D6S297. No known
      genes were present in the deleted region. Because the homozygous deletion might
      affect the expression of nearby genes, we analyzed the expression of the two
      closest known genes flanking the deletion, RNASE6PL and RSK-3. The expression of
      these genes were unaffected by the homozygous deletion, suggesting that the
      functional target of the deletion is located between these two genes. A search of
      the region against expressed sequence tag (EST) databases revealed that it
      contained four sets of expressed sequences. The first expressed sequences were
      derived from a LINE repetitive element and were considered unlikely to represent
      a tumor suppressor gene. The other expressed sequence tags identified did not
      show homology to known genes and are currently being investigated. This data may
      significantly reduce the magnitude of the search for the 6q tumor suppressor gene
      as it suggests a small area as a prime target for investigation.

PMID- 11578811
TI  - E-cadherin expression is commonly downregulated by CpG island hypermethylation in
      esophageal carcinoma cells.
AB  - E-cadherin, a cell adhesion molecule, is regarded as an invasion-suppressor
      molecule and a prognostic marker in many types of human cancers. Downregulation
      of E-cadherin is common in esophageal carcinoma and is associated with an
      increase in invasive and metastatic potential. To study the mechanisms
      responsible for inactivation of this gene in esophageal squamous cell carcinoma
      (ESCC), we investigated the methylation status around the 5' promoter region of E
      cadherin gene of six ESCC cell lines by methylation-specific polymerase chain
      reaction, and compared it with E-cadherin protein and mRNA expression. We also
      studied the methylation status of 20 ESCC clinical specimens. Methylation was
      noted in four of the six cell lines (one fully methylated and three partially
      methylated). The completely methylated cell line lacked E-cadherin protein
      expression and mRNA transcription. E-cadherin expression and transcription were
      reduced in a partially methylated cell line but preserved in the other partially
      methylated cell lines. Treatment of E-cadherin-negative carcinoma cells with the
      demethylating agent, 5-aza-2'-deoxycytidine, induced re-expression of the gene. A
      high frequency of methylation (16/20, 80%) was also noted in the 20 ESCC clinical
      samples. Our results indicate that 5' CpG island methylation is common in
      esophageal carcinoma and may play an important role in downregulation of E
      cadherin.

PMID- 11578812
TI  - Serum levels of matrix metalloproteinase 2 in patients with breast cancer.
AB  - Matrix metalloproteinases (MMPs) have been reported to be associated with
      invasive and metastatic behaviors of human malignant tumors. However, there is
      still limited knowledge about the role of matrix metalloproteinases-2 (MMP-2) in
      breast cancer. This study was designed with the aim to elucidate the possible
      relationship between the preoperative circulating MMP-2 and breast cancer. Fifty
      seven consecutive patients with invasive breast cancer undergoing surgery were
      prospectively included and evaluated. Venous blood samples were collected before
      the surgery. Sera were obtained by centrifugation, and stored at -70 degrees C
      until assayed. The control group consisted of 12 patients with benign breast
      tumor (six with fibrocystic disease and six with fibroadenoma). Serum
      concentrations of MMP-2 were measured by the quantitative sandwich enzyme
      immunoassay technique. The data on primary tumor stage, age, estrogen receptor,
      lymph node status, and TNM staging were reviewed and recorded. The mean value of
      serum MMP-2 in patients with invasive breast cancer was 694.3+/-140.5 ng/ml and
      those of control group were 593.3+/-134.0 ng/ml and the difference was
      significant (P=0.026). Furthermore, there were significantly higher serum levels
      of MMP-2 in the patients with more advanced primary tumor staging (P=0.005), in
      the patients with more advanced lymph node status(P=0.011) and in the patients
      with more advanced TNM staging (P<0.001). In multivariate analysis, TNM staging
      (P<0.001) appeared as independent factor regarding the significant higher serum
      levels of MMP-2. Patients with more advanced TNM staging were shown to have
      higher serum MMP-2 levels. Thus preoperative serum MMP-2 levels might reflect the
      severity of invasive breast cancer and deserve further evaluation.

PMID- 11578813
TI  - Glucose catabolism in the rabbit VX2 tumor model for liver cancer:
      characterization and targeting hexokinase.
AB  - The rabbit VX2 tumor when implanted in the liver has proven convenient as a model
      for studying hepatocellular carcinomas. However, its metabolic properties have
      not been well studied. Significantly, studies described here show that the VX2
      tumor exhibits a high glycolytic/high hexokinase phenotype that is retained
      following implantation and growth in rabbit liver. In addition, results of a
      limited screen show that the glycolytic rate is inhibited best by 2-deoxyglucose
      (2DOG) and 3-bromopyruvate (3BrPA), the former compound of which is
      phosphorylated by hexokinase but not further metabolized, while the latter
      directly inhibits hexokinase. Finally, when tested on hepatoma cells in culture
      both inhibitors facilitated cell death. These studies underscore the usefulness
      of the VX2 tumor model for the study of advanced liver cancer and for selecting
      anti-hepatoma agents.

PMID- 11578814
TI  - Elevated levels of high-mobility-group chromosomal proteins, HMGA1, in murine
      skin carcinoma.
AB  - The high-mobility-group, HMGA1 (formerly HMGI(Y)) chromosomal proteins are known
      to be involved in gene regulation and their high expression is associated with
      neoplastic transformation of cells and metastatic tumor progression. Here, we
      present our results on the expression of HMGA1 in murine skin carcinoma as
      detected by acid-urea electrophoresis, reverse-phase high-performance liquid
      chromatography and Western blot. The enhanced expression of HMGA1 proteins
      directly correlates with the extent of cellular atypia and neoplastic changes
      noticed in the histopathology of tumor and suggest a potential use of these
      proteins as marker for determining the grade of skin tumor.

PMID- 11578815
TI  - Strong association of a novel Tau promoter haplotype in progressive supranuclear
      palsy.
AB  - The microtubule associated protein, tau, is found in fibrillar lesions that
      characterise progressive supranuclear palsy (PSP) and related tauopathies.
      Mutations in the tau gene in frontotemporal dementia with parkinsonism linked to
      chromosome 17 (FTDP-17) and genetic association of the H1 haplotype of the tau
      gene with PSP has firmly established a direct role for tau in disease
      pathogenesis. However, the functional significance of the tau genetic association
      in PSP is unknown. We analysed the tau gene promoter sequence and identified two
      novel single nucleotide polymorphisms. Here we report the genetic association of
      a novel tau promoter haplotype with PSP which may influence tau transcription.

PMID- 11578816
TI  - Evidence for an estrogen-like action of raloxifene upon the hypothalamic
      pituitary unit: raloxifene inhibits luteinizing hormone secretion and stimulates
      prolactin secretion in ovariectomized female rats.
AB  - Selective estrogen receptor modulators (SERMs) constitute a new family of drugs
      with growing interest in the management of estrogen-associated pathology.
      Raloxifene is a SERM that is used to treat and prevent osteoporosis in
      postmenopausal women. The actions of raloxifene on bone, breast, uterus and serum
      cholesterol have been widely analyzed, but very few studies have been carried out
      to evaluate whether raloxifene has an estrogenic activity upon the hypothalamic
      pituitary axis in the rat. For this purpose, adult female rats were
      ovariectomized or sham ovariectomized. One week later, the rats were implanted
      with intracardiac canullae and 24 h after injected daily with raloxifene (500
      microg/rat/day) or vehicle for 5 days. One hour after the last injection, blood
      samples were obtained at 5 min intervals for a 3 h. period (10:00-13:00 h). Our
      results indicate that raloxifene inhibits the pulsatile nature of the post
      ovariectomy hypersecretion of luteinizing hormone (LH) and increases prolactin
      (PRL) secretion in ovariectomized animals. These effects are suggestive of an
      estrogenic activity of raloxifene on LH and PRL secretion in ovariectomized
      females.

PMID- 11578817
TI  - Memory improving actions of gabapentin in mice: possible involvement of central
      muscarinic cholinergic mechanism.
AB  - Male CF-1 mice were tested 48 h after training on a one trial step-through
      inhibitory avoidance task. Immediately post-training, intraperitoneal (i.p.)
      injections of the antiepileptic gabapentin (1-(aminomethyl) cyclohexaneacetic
      acid) (GBP, 10 mg/kg) enhanced retention performance. The effect was prevented by
      atropine, a central muscarinic cholinergic receptor antagonist (0.5 mg/kg, i.p.)
      administered after training but 10 min prior to GBP treatment. In contrast,
      neither methylatropine (0.5 mg/kg, i.p.), a peripherally acting muscarinic
      receptor blocker, nor mecamylamine (5 mg/kg, i.p.) or hexamethonium (5 mg/kg,
      i.p.), two cholinergic nicotinic receptor antagonists, prevented the effects of
      post-training GBP on retention performance. Low subeffective doses of the central
      acting anticholinesterase physostigmine (35 mg/kg, i.p.) administered immediately
      after training, and GBP (5 mg/kg, i.p.), given 10 min after training,
      significantly enhanced retention performance. The effects of GBP (5 mg/kg, i.p.)
      were not influenced by the peripherally acting anticholinesterase neostigmine
      (150 mg/kg, i.p.). Considered together, these findings suggest a disinhibitory
      action of GBP on the activity of central muscarinic cholinergic mechanisms that
      are involved in memory consolidation.

PMID- 11578818
TI  - Contralateral treatment with lidocaine reduces spinal neuronal activity in
      mononeuropathic rats.
AB  - In anaesthetised and paralysed rats with chronic constriction of the sciatic
      nerve, the effects of subcutaneous contralateral lidocaine (100 microl) on the
      activity of lumbar (L(4)-L(5)) wide dynamic range neurons ipsilateral to the
      constriction have been investigated. The results show reduction of the
      spontaneous hyperactivity for 60 min; suppression or reduction of the responses
      to contralateral noxious stimulation for 60 min; lack of effect on the responses
      to ipsilateral noxious stimulation, except for the afterdischarge duration,
      reduced for 60 min. The finding that the altered neuronal activity following
      peripheral nerve injury associated to behavioural signs of neuropathic pain, can
      be reduced by contralateral treatment, may provide further suggestions to
      neuropathic pain mechanisms and management.

PMID- 11578819
TI  - Differential synaptic localization of GluR2 and EAAC1 in the macaque monkey
      entorhinal cortex: a postembedding immunogold study.
AB  - The synaptic distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic
      acid receptor subunit GluR2 and neuronal glutamate transporter subunit EAAC1 were
      studied using immunogold in layer II of the macaque monkey entorhinal cortex.
      Immunoreactivity for EAAC1 and GluR2 was frequent at asymmetric synapses and
      their associated membrane. The synaptic localization of EAAC1 differed
      considerably from that of GluR2, in that GluR2 immunolabelling was most commonly
      located within the postsynaptic density, but EAAC1 localization was more
      heterogeneous and was predominant at the edge of postsynaptic densities and
      perisynaptic zones. Since EAAC1 may play an important role in clearing glutamate
      from the synaptic cleft and intercellular spaces, the high perisynaptic
      expression of EAAC1 in these neurons could presumably offer a powerful mechanism
      through which high concentrations of glutamate could be efficiently removed from
      the synapses following release and interaction with glutamate receptors. The
      distribution of EAAC1 may also offer protection for these neurons against
      excessive glutamatergic stimuli that may occur under certain pathological
      conditions.

PMID- 11578820
TI  - Drebrin expression is increased in spinal motoneurons of rats after axotomy.
AB  - Drebrin has been known to act on actin filaments at dendritic spines to cause
      morphological change, and might be related to the plasticity of synaptic
      transmission. In the present study, changes of drebrin were examined
      immunohistochemically in the spinal motoneurons of rats following unilateral
      sciatic nerve transection. Drebrin-immunoreactivity (-ir) in the motoneurons was
      significantly increased on the lesioned side after 3 days. Confocal laser
      scanning microscopic images of the motoneurons revealed conspicuous increase in
      drebrin in the submembranous region of the cells. After 10 weeks, drebrin-ir on
      the lesioned side decreased to a level not significantly different from that on
      the unlesioned side. The results suggested that drebrin played important roles in
      synaptic restoration in axotomized motoneurons.

PMID- 11578822
TI  - Drinking related direct current positive potential shift in the human EEG depends
      on thirst.
AB  - Scalp recorded direct current (DC)-potential shifts were examined in 11 human
      subjects who had either thirsted for 16 h or had quenched thirst before
      recordings. The recording epoch included a 3-min baseline, an interval of about 5
      min during which subjects drank 400 ml of water, and a 7-min post-drinking
      interval. Consistent with previous data, when thirsty, subjects displayed a
      widespread negative DC-potential shift during drinking which was replaced by a
      positive DC shift at the transition to the post-drinking interval. The positivity
      after drinking lasted for about 2 min and averaged 146 microV at frontal
      recording sites. Quenching thirst before recordings reduced the positive DC
      potential shift upon drinking, whereas changes in preceding drinking related DC
      negativity appeared to be secondary. The post-drinking positive DC-potential
      shift depending on the subject's motivational state can be considered an
      indicator of reward associated with quenching thirst, pointing to a lowered
      frontocortical excitability during reward.

PMID- 11578821
TI  - Bicarbonate and thiocyanate ions affect the gating of gamma-aminobutyric acid(A)
      receptors in cultured rat cortical cells.
AB  - The ionophore function of gamma-aminobutyric acid(A) (GABA(A)) receptors was
      studied by whole-cell patch clamp electrophysiology in primary cultures of rat
      cerebral cortex. Chloride ions were replaced for SCN(-) (thiocyanate) and HCO(-3)
      (bicarbonate) ions. The EC(50) values of the GABA(A) agonist muscimol (HCO(
      3)>Cl(-)>SCN(-)) varied parallel with the free energies of dehydration of the
      anions, while the inhibition constants of the GABA(A) antagonist bicuculline
      methiodide were not affected. These findings might be relevant in the
      interpretation of the contribution of HCO(-3) versus Cl(-) currents to the
      pharmacological differences between depolarizing and hyperpolarizing GABA
      responses.

PMID- 11578823
TI  - Propofol suppresses a hyperpolarization-activated inward current in rat
      hippocampal CA1 neurons.
AB  - We examined the effect of propofol and thiopental, intravenous anesthetics, on
      the hyperpolarization-activated inward current (I(H)), whose functional role on
      the neuronal activity has been evaluated. Whole-cell recordings of I(H) evoked by
      hyperpolarizing step pulses were taken from hippocampal CA1 neurons in rat brain
      slices. Propofol reduced I(H) current in a dose-dependent manner. However,
      thiopental had no significant effect on the activation of I(H). According to the
      functional role of I(H), the suppression of I(H) should result in a reduction of
      neuronal activity. We suggest that the effectiveness of propofol as an
      anticonvulsant or an antiemetic is associated with the blockade of the I(H)
      channel.

PMID- 11578824
TI  - Conduction velocity of the spinothalamic tract in humans as assessed by CO(2)
      laser stimulation of C-fibers.
AB  - We measured the conduction velocity (CV) of C-fibers in the spinothalamic tract
      (STT) following stimulation with a CO(2) laser using a new method. We delivered
      non-painful laser pulses to tiny areas of the skin overlying the vertebral
      spinous processes at different levels from the 7(th) cervical (C7) to the 12(th)
      thoracic (T12), and recorded cerebral evoked potentials in 11 healthy men. We
      used the term "ultra-late laser evoked potentials" (ultra-late LEPs), since the
      peak latency was much longer than that for conventional LEPs related to Adelta
      fibers following painful laser stimulation (late LEPs). The mean CV of C-fibers
      in the STT was 2.2+/-0.6 m/s, which was significantly lower than the CV of the
      Adelta-fibers (10.0+/-4.5 m/s). This technique is novel and simple, and should be
      useful as a diagnostic tool for assessing the level of spinal cord lesions.

PMID- 11578825
TI  - Protein kinase C gamma-like immunoreactivity in the substantia gelatinosa of the
      medullary dorsal horn of the rat.
AB  - We examined protein kinase C gamma-immunoreactivity (PKCgamma-IR) in the
      substantia gelatinosa (SG) of the rat medullary dorsal horn (MDH). The density of
      PKCgamma-IR in the MDH was most intense in the SG. The number of neurons with
      PKCgamma-IR were also much larger in the SG than in the other layers of the MDH.
      Double-immunohistochemical studies indicated light and electron microscopically
      that substance P-containing fibers and I-B4 (isolectin from Bandeiraea
      simplicifolia)-labeled fibers made synapses on SG neurons with PKCgamma-IR,
      indicating that SG neurons with PKCgamma might receive nociceptive primary
      afferent fibers. The results support the notion that PKCgamma in the MDH may
      contribute to the regulation of the nociception.

PMID- 11578826
TI  - Gonadal steroid receptor mRNA in catecholaminergic nuclei of the canary
      brainstem.
AB  - Steroid actions in the song system may be modulated by ascending inputs from
      catecholaminergic (CA) brain nuclei; however, whether these nuclei contain
      steroid receptors is unknown. Here, we compared the distribution of androgen
      receptor (AR) and estrogen receptor-alpha (ER-alpha) mRNA with that of tyrosine
      hydroxylase immunoreactivity (TH-IR) in the brainstems of male canaries. Areas
      containing AR and ER-alpha mRNA overlapped with areas containing TH-IR cell
      bodies in the locus ceruleus and the area ventralis of Tsai. The substantia nigra
      and the midbrain central gray contained both TH-IR and AR mRNA. The presence of
      AR and ER-alpha within CA cell groups suggests that sex steroid hormones may
      modulate song production at the site of CA synthesis.

PMID- 11578827
TI  - Prefrontal cortical hyperactivity in patients with sympathetically mediated
      chronic pain.
AB  - Chronic pain continues to impose a large burden of suffering, yet its neural
      correlates remain poorly understood. In sympathetically mediated chronic pain
      (SMP), peripheral sympathetic blockade temporarily relieves this pain, so that
      related neural activity can be studied without perturbing sensory inputs. We used
      functional magnetic resonance imaging and thermal painful stimuli applied to the
      chronically painful body site, before and after sympathetic blockade, to examine
      the cortical network of chronic pain. The chronic SMP state was associated with a
      widely spread prefrontal hyperactivity, increased anterior cingulate activity and
      decreased activity in the thalamus contralateral to the body side suffering from
      SMP, but was unrelated to sensorimotor activity. Ineffective sympathetic blocks,
      i.e. blocks that did not diminish the SMP pain, did not change the cortical
      responses to the painful thermal stimulus; while effective placebo resulted in
      similar responses to those of effective blocks. These findings provide evidence
      for abnormal brain responses to pain in patients with chronic SMP, which engages
      prefrontal/limbic networks more extensively than in acute pain-states.

PMID- 11578828
TI  - Modulation of event-related potentials in normal human subjects by visual divided
      attention to spatial and color factors.
AB  - We investigated how visual event-related potentials (ERPs) are modulated by
      visual divided attention using an S1-S2 paradigm. Stimulus S2 consisted of non
      target stimuli (Stimulus 1, 2, 3) and a target stimulus (Stimulus 4). The
      spatial/color factor was compared between S1 and S2: same/same (Stimulus 1);
      same/different (Stimulus 2); different/same (Stimulus 3); and different/different
      (Stimulus 4). The P1/N1 (90 approximately 150 ms) showed significantly greater
      amplitude in Stimulus 3 than in Stimuli 1 and 2. The N2 (230 approximately 290ms)
      showed significantly greater amplitude in Stimulus 2 than in Stimuli 1 and 3. We
      assumed that the P1/N1 was related to spatial attention, enhanced by alterations
      to the spatial factor, and that the N2 was related to color attention, enhanced
      by alterations to the color factor.

PMID- 11578829
TI  - L-isoform but not S-isoform of myelin associated glycoprotein promotes neurite
      outgrowth of mouse cerebellar neurons.
AB  - Myelin associated glycoprotein (MAG) has growth promoting effect on mouse
      cerebellar neurons. In the present study, we examined which isoform of MAG has
      the effect. cDNA for L-MAG and S-MAG was stably transfected into BALB/c 3T3
      cells, on which cerebellar neurons were cultured. The neurons were stained with
      antibody against microtubule-associated protein-2. Neurites of the neurons
      cultured on cells expressing L-MAG extended significantly further than those
      cultured on cells expressing S-MAG or on control cells. Therefore, intracellular
      domain of MAG may have the potential to affect MAG-neurite interaction.

PMID- 11578830
TI  - The glutamate receptor agonist, AMPA, induces acetylcholine release in guinea pig
      cochlea; a microdialysis study.
AB  - Acetylcholine (Ach) has been considered a major neurotransmitter in the inner ear
      efferent nerve endings. A bioassay analysis has shown that the electrical
      stimulation of the crossed olivocochlear bundle increased the Ach-like activity
      in the perilymph. Applying in vivo microdialysis techniques and high-performance
      liquid chromatography to the perilymph, the change of Ach level was thus measured
      before and after alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA), a glutamate receptor agonist, was added to the perfusate. Ach was only
      detectable when the perfusate contained an acetylcholinesterase inhibitor. The
      level of Ach increased 2-3-fold immediately after AMPA was administered. Our data
      suggest that the afferent stimulation, such as the administration of AMPA, may
      therefore induce the release of Ach from the efferent nerve endings.

PMID- 11578831
TI  - Effects of chronic nerve cuff and intramuscular electrodes on rat triceps surae
      motor units.
AB  - In order to assess the long-term effects of implanted electrodes on motor unit
      properties, we studied triceps surae (TS) motor units in rats implanted for 3-10
      months with a tibial nerve cuff electrode for H-reflex elicitation and
      intramuscular electrodes for recording TS electromyographic activity. Motor units
      with sag from implanted rats displayed greater tetanic force than those from
      unimplanted rats. Motor units without sag had shorter twitch contraction times.
      This disrupted the relationship between sag and contraction time that was always
      present in unimplanted rats. These differences were consistent with a small
      degree of muscle denervation and subsequent reinnervation. Further analyses
      ascribed this effect to the nerve cuff rather than to the intramuscular
      electrodes. Comparable changes in motor unit properties may occur in humans with
      implanted nerve cuffs.

PMID- 11578832
TI  - Aluminum promotes neuronal plasticity events in a mouse neuroblastoma cell line.
AB  - The effects of aluminum(III) on microtubular meshwork have been investigated
      using cultured murine neuroblastoma cells grown in a medium containing aluminum
      lactate at defined metal concentrations (10-20 microM). A role of aluminum(III)
      in promoting neuronal plasticity events is suggested. These events including
      sprouting and neurite outgrowth are associated with an increased tyrosine-tubulin
      (Tyr-Tub) expression, which can be due to the enhanced needs of recently formed,
      highly dynamic microtubules typical of neuronal plasticity. After 48 and 72 h
      aluminum exposure, an upregulation of Tyr-Tub expression is detected and this is
      concentration-dependent. A high amount of Tyr-Tub is observed also in non-treated
      cells, although later than in aluminum-exposed cells. Thus, it is possible that
      aluminum(III) accelerates neuronal plasticity events, for which Tyr-Tub is
      confirmed to be a useful marker.

PMID- 11578833
TI  - Photoperiod and social cues influence the medial amygdala but not the bed nucleus
      of the stria terminalis in the Siberian hamster.
AB  - We investigated whether the posterodorsal nucleus of the medial amygdala (MePD)
      and the posteromedial nucleus of the bed nucleus of the stria terminalis (BSTpm)
      undergo structural changes in response to photoperiod or social environment in
      the Siberian hamster, a seasonally breeding rodent. Adult male hamsters were
      either kept in long days (LD; 15:9 h light:dark) from birth or were transferred
      at 12-16 weeks of age to short days (SD; 8:16) and housed with a male conspecific
      for 11 weeks. Other males were transferred to SD but were housed with an
      unrelated female conspecific from LD. Males transferred to SD without a female
      cagemate displayed testicular regression, but males transferred to SD with a
      female cagemate did not. The regional volume and average soma size of the BSTpm
      and the MePD were estimated using Nissl-stained brain sections. Neither
      photoperiod nor social condition modified either of the BSTpm measures. Among
      males housed in same-sex groups, the average soma size in the MePD was
      significantly smaller in SD males than in LD males. Cohabitation with a female
      resulted in MePD volumes indistinguishable from LD males. These results indicate
      that the MePD, a nucleus implicated in socio-sexual behavior, can respond to
      photoperiodic as well as to social cues.

PMID- 11578834
TI  - Age-related changes in brain neuromagnetic responses to face perception in
      humans.
AB  - In order to investigate the effects of ageing on face perception, we studied the
      magnetic responses to face images in 15 young (19-38 years) and 10 elderly (51-81
      years) subjects. Face-specific responses (160mF), which originate in the inferior
      occipitotemporal cortices, and face non-specific responses (100m), which
      originate in the primary visual cortices, were evoked in all subjects. Averaged
      peak latency of the 160mF in the elderly group (174.0+/-9.1 ms) was significantly
      longer (P<0.0005) than that in the young group (161.5+/-5.1 ms), while no inter
      group difference was found in the 100m latency. There was a significant
      correlation between age and 160mF latency (+0.35 ms/year, R=0.747) suggesting age
      related decline of face perception.

PMID- 11578835
TI  - Imaging postsynaptic activities of teleost thalamic neurons at single cell
      resolution using a voltage-sensitive dye.
AB  - Optical recording of neuronal activities using voltage-sensitive dyes (VSDs) is a
      useful method for simultaneous multi-site recording. However, it has been rather
      difficult to distinguish optical signals from individual, identified cells. We
      applied the optical recording technique using a high-speed charge coupled device
      (CCD) imaging system to a teleost thalamic nucleus, corpus glomerulosum (CG)
      which has a well-defined histological organization and large postsynaptic
      dendrites. Patch-like dye (di-4-ANEPPS) signals were observed in the dendritic
      layer of the CG in response to afferent nerve stimulations. These responses were
      completely blocked by an alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionate
      (AMPA) receptor antagonist, did not propagate, and the size of the patches were
      close to that of a single dendritic tip of the 'large cell'. Thus, we found that
      these patch-like VSD signals most likely represent postsynaptic potentials at
      individual dendritic tips of the large cells.

PMID- 11578837
TI  - Volitional selection of direction in the generation of anticipatory ocular smooth
      pursuit in humans.
AB  - Anticipatory smooth pursuit eye movements cannot normally be generated in the
      absence of a moving target. However, repeated presentation of identical target
      motion stimuli, preceded by warning cues, leads to the build up of anticipatory
      smooth pursuit prior to target onset. These anticipatory responses arguably
      depend more on motor habit than cognitive expectations. Here, we show that
      directional cues, concomitant with a timing cue, may be used to initiate
      predictive (velocity scaled) movements in response to target stimuli of random
      direction. Furthermore, we show stored velocity and timing information may be
      directionally transferred, thus allowing predictive movements in a novel
      direction. This demonstrates the internal origin of these movements and their
      volitional as opposed to reflexive nature.

PMID- 11578836
TI  - Effects of hypothermia on neonatal hypoxic-ischemic brain injury in the rat:
      phosphorylation of Akt, activation of caspase-3-like protease.
AB  - Neuroprotective mechanisms of hypothermia have not been clearly established
      especially in the immature brain. To investigate the effect of hypothermia on
      cell death and cell survival signal pathways, we studied caspase-3-like activity
      and activation of Akt in a rat model of neonatal hypoxic-ischemic (H-I) brain
      injury. Seven-day-old rats underwent a combination of left common carotid artery
      ligation and exposure to 8% O(2) for 1-h (n=32). During recovery, the body
      temperature was reduced to 30 degrees C for 24 h in 16 animals, but was kept at
      37 degrees C in 16 animals. Post-ischemic hypothermia was shown to diminish the
      caspase-3-like activity compared to normothermia at 6 and 24 h after H-I. Phospho
      Akt was increased during the early reperfusion period after H-I in the
      normothermia group, but hypothermia rather decreased this enhanced
      phosphorylation of Akt following H-I. These results indicated that hypothermia
      may have some depressant effects on both cell death and cell survival signal
      pathways, and that Akt conceivably may not play a major role in the
      neuroprotective effect of hypothermia in the immature brain.

PMID- 11578838
TI  - Advanced glycation endproducts change glutathione redox status in SH-SY5Y human
      neuroblastoma cells by a hydrogen peroxide dependent mechanism.
AB  - The reaction of proteins with reducing sugars leads to the formation of 'advanced
      glycation endproducts' (AGEs). They accumulate in Alzheimer's disease brain in
      the vicinity of beta-amyloid plaques. AGEs are cytotoxic by a mechanism involving
      reactive oxygen species, which implies that they could compromise glutathione
      redox status. In this study, we show that AGEs (BSA-AGE and beta-amyloid-AGE)
      persistently increase the ratio of oxidized to reduced glutathione in a dose- and
      time-dependent manner in SH-SY5Y neuroblastoma cells. The level of oxidized
      glutathione accounted to 10-14% and persisted for up to 24 h in the presence of
      added AGEs. In contrast, the unmodified beta-amyloid peptides A beta (1-40) and A
      beta (25-35) had no significant effect on glutathione redox status. The AGE
      induced increase in oxidized glutathione could be prevented by the radical
      scavengers N-acetylcysteine, alpha-lipoic acid and 17beta-estradiol or by
      application of catalase, indicating that superoxide and hydrogen peroxide
      production precedes the AGE-mediated depletion of reduced glutathione.

PMID- 11578839
TI  - Changes in P2Y and P2X purinoceptors in reactive glia following axonal
      degeneration in the rat optic nerve.
AB  - Purinoceptors have been shown to be important in mediating Ca(2+) signalling in
      glial cells and it has been proposed that they may have a role in their response
      to injury. To investigate this, the glial response to adenosine 5'triphosphate
      (ATP) was measured in situ, in optic nerves from juvenile rats that were
      enucleated at postnatal day (P) 1; age-matched normal nerves were used as
      controls. The optic nerve is a typical central nervous system (CNS) white matter
      tract containing axons and glial cells, but not neurones or synapses. Following
      neonatal enucleation, axons degenerate and oligodendrocytes do not develop, so
      that the optic nerve is populated predominantly by reactive astrocytes, with a
      minor population of activated microglia. Application of 1 mM ATP evoked a large
      and rapid increase in glial [Ca(2+)](i) in fura-2 ratiometric whole nerve
      recordings from normal and gliotic axon-free nerves. Significantly, the response
      to ATP had a prolonged duration in gliotic axon-free nerves and there was as
      shift in the agonist rank order of potency from ATP = ADP > UTP >> alpha,beta
      metATP to ATP > ADP = UTP = alpha,beta-metATP. The results indicate an in situ
      role for ATP signalling in reactive astrocytes, via metabotropic P2Y(1) and
      P2Y(2/4) purinoceptors and ionotropic P2X purinoreceptors. The change in the
      purinoceptor profile following axon degeneration suggests a special role for P2X
      purinoceptors in mediating the glial reaction to CNS injury.

PMID- 11578840
TI  - Single systemic dose of vigabatrin induces early proconvulsant and later
      anticonvulsant effect in rats.
AB  - Vigabatrin (VGB), an inhibitor of gamma-aminobutyric acid-aminotransferase,
      exhibits an antiepileptic effect but several studies indicate that its effect may
      be biphasic. A time course of an effect of a single injection of VGB on
      hippocampal epileptic afterdischarges (AD) elicited by an electric stimulation of
      the angular bundle was examined in adult rats with chronically implanted
      electrodes. VGB (600 or 1200 mg/kg intraperitoneally) proved to be an efficient
      anticonvulsant in the intervals of 24 and 48 h--duration of ADs was shortened and
      behavioral phenomena were less intense. In contrast, ADs were lengthened 4 h
      after administration. The biphasic effect of VGB was demonstrated, the initial
      proconvulsant effect might be due to a different onset of VGB action in
      individual brain structures, but an additional mechanism of action cannot be
      excluded.

PMID- 11578841
TI  - Expression of interleukin-1 beta in lipopolysaccharide stimulated monocytes
      derived from patients with aneurysmal subarachnoid hemorrhage is correlated with
      cerebral vasospasm.
AB  - Cerebral arterial vasospasm is a frequent complication after aneurysmal
      subarachnoid hemorrhage (SAH). Immunological activation may affect the
      development of vasospasm. This study measured the cytokines released from
      lipopolysaccharide-stimulated monocytes of SAH patients. We measured cerebral
      artery diameters before and after surgery for SAH. The activation index of
      interleukin-1 beta (IL-1 beta), but not tumor necrosis factor-alpha (TNF-alpha),
      was higher in patients with symptomatic vasospasm (5.6+/-1.7; n=11) than in
      patients without (1.8+/-0.4; n=11) (P=0.039). Furthermore, the IL-1 beta
      activation index was correlated with the degree of the postoperative angiographic
      vasospasm (correlation coefficient=-0.66, P=0.007). Individual variation in
      systemic immune activation, measured by monocyte-derived IL-1 beta expression
      levels after stimulation, may be associated with the development of vasospasm
      after aneurysmal SAH.

PMID- 11578842
TI  - Propofol activates vanilloid receptor channels expressed in human embryonic
      kidney 293 cells.
AB  - Propofol (2,6-diisopropylphenol) is an intravenous anesthetic agent structurally
      unrelated to any other intravenous anesthetics. We examined the effect of
      propofol on a rat vanilloid receptor that was expressed in the human embryonic
      kidney (HEK) 293 cells by using calcium imaging method. Propofol caused a
      concentration-dependent increase in [Ca(2+)](i) in the HEK293 cells with the
      receptor. These responses were inhibited by removing extracellular calcium ions.
      The propofol-evoked increase in [Ca(2+)](i) in the HEK293 cells with the receptor
      was partially inhibited by capsazepine, a competitive antagonist of capsaicin. We
      conclude that propofol acts as an agonist for the receptor.

PMID- 11578843
TI  - Riluzole (2-amino-6-trifluoromethoxy benzothiazole) attenuates MPTP (1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity in mice.
AB  - The protective effects of 2-amino-6-trifluoromethoxy benzothiazole (riluzole), a
      Na(+) channel blocker with antiglutamatergic activity were investigated in the
      model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced depletion of
      dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
      levels in mice. The mice were injected intraperitoneally (i.p.) with four
      administrations of MPTP (10 mg/kg) at 1 h intervals and then the brains were
      analyzed at 3 and 7 days after the treatments. Dopamine, DOPAC and HVA levels
      were significantly decreased in the striatum 3 days after MPTP treatments.
      Riluzole dose-dependently antagonized the MPTP-induced decrease in dopamine,
      DOPAC and HVA levels in the striatum. MPTP treatment also caused a severe
      decrease in the amount of nigral tyrosine hydroxylase protein (TH) and microtuble
      associated protein 2 (MAP 2) and produced a marked increase in the striatal glial
      fibrillary acidic protein (GFAP). Our immunohistochemical study with TH and MAP 2
      staining showed that riluzole can protect against MPTP-induced neuronal damage in
      the substantia nigra. Furthermore, riluzole markedly increased the striatal GFAP
      positive astrocytes 3 days after MPTP treatments. These results suggest that
      riluzole is effective against MPTP-induced neurodegeneration of the nigrostriatal
      dopaminergic neuronal pathway. Our findings also may provide a rationale for the
      identification of astrocytes as a prominent target for the development of new
      therapies of Parkinson's disease.

PMID- 11578844
TI  - Preterm infants prefer to be awake at night.
AB  - Wakefulness distribution during a 24-h period was studied in ten low-risk preterm
      and near term infants through video-recording. The highest amount of wakefulness
      was found in the night-time period between 02:00 and 05:00 h. This result is
      different from what was observed in infants during the first year of life, and
      similar to what was found in the foetus.

PMID- 11578845
TI  - Joint deformity patterns in severely physically disabled patients.
AB  - Deformity patterns of the spine and upper and lower extremities were investigated
      in 64 patients with severe physical disability. Among the subjects, C-shaped and
      S-shaped scoliosis was found in 48 and nine, respectively. The hips were
      windblown in 20, adducted in 22, and abducted in seven. Knees were flexed in 39
      and extended in four. Deformities of the ankle and upper extremities were
      variable. The most common combination, which was C-shaped scoliosis with
      convexity to the adducted side of hips, windblown hips, flexed knees, and
      dorsiflexed ankles, was noted among nine patients. Joint deformity patterns in
      the 43 patients with spastic tetraplegia were not significantly different from
      those in the 21 patients with dyskinesia.

PMID- 11578846
TI  - Seizure frequency and characteristics in children with Down syndrome.
AB  - Seizures have not historically been considered a major component of Down
      syndrome. We examined the prevalence of epileptic seizures in 350 children and
      adolescents with Down syndrome evaluated at a regional center between 1985 and
      1997. Results showed that 28 patients (8%) had epileptic seizures: 13 (47%)
      partial seizures; 9 (32%) infantile spasms, and 6 (21%) generalized tonic-clonic
      seizures. In the infantile spasm group, there was no relationship between the
      initial electroencephalogram (EEG) pattern and response to treatment or long-term
      seizure control, or between type of pharmacologic treatment (valproic acid,
      adrenocorticotropic hormone or both) and clinical remission, EEG normalization or
      long-term seizure control. Neurodevelopmental outcome was poor despite good
      seizure control in the infantile spasm group. This regional study reinforces the
      relative association of seizures and Down syndrome. A prospective study including
      a national/international registry with emphasis on developmental assessment and
      long-term follow up is warranted.

PMID- 11578847
TI  - Development of lysosomal storage in mice with targeted disruption of the beta
      galactosidase gene: a model of human G(M1)-gangliosidosis.
AB  - A deficiency of lysosomal acid beta-galactosidase leads to G(M1)-gangliosidosis
      in humans, which progressively and profoundly affects the brain and other organs
      mainly in the early infantile period. We report the pathology of mice with
      targeted disruption of the beta-galactosidase gene. In the central nervous
      system, vacuolated neurons appeared in the spinal cord 3 days after birth. The
      vacuolation extended to neurons in the brainstem, cerebral cortex, hippocampus
      and thalamus and ballooning neurons became prominent with age. The vacuolation
      also appeared in Purkinje cells without a marked ballooning change. Reactive
      astrogliosis in the entire brain was marked at the terminal stage of the disease.
      Immunohistochemical study using anti-ganglioside G(M1) and G(A1) antibodies
      revealed extensive accumulation of G(M1) and G(A1) in the cerebral neurons. In
      the liver, however, accumulation of G(M1) was localized in the cytoplasm of
      hepatocytes, whereas that of G(A1) was localized in foamy macrophages and Kupffer
      cells. There were no significant abnormalities in the bone, bone marrow, or
      cornea at any stage. Although there are some phenotypic and biochemical
      differences between this knockout mouse and human GM1 gangliosidosis, the mouse
      will be a useful model for therapeutic trials for the human disease.

PMID- 11578848
TI  - Serial magnetic resonance imaging findings in mucopolysaccharidosis IIIB
      (Sanfilippo's syndrome B).
AB  - Sanfillippo B syndrome (mucopolysaccharidosis (MPS) III, type B) is characterized
      by mild expression of the characteristic 'Hurler' phenotype and a severe central
      nervous system involvement. We report three patients with Sanfilippo B syndrome,
      referred to our clinic because of peculiar facies, delay in language development
      and behavioral problems, at the ages of 4, 3 and 5 years, respectively. At
      presentation they manifested clinical features of MPS, severe developmental
      retardation, radiological features of dysostosis mutiplex, as well as
      neurophysiological findings suggestive of carpal tunnel syndrome and
      sensorineural hearing impairment. Due to marked urinary excretion of heparan
      sulfate, as well as deficiency of alpha-N-acetylglucosaminidase in leukocytes,
      the diagnosis of Sanfilippo B syndrome was made. Serial brain magnetic resonance
      imaging (MRI) at different ages demonstrated white matter abnormalities, cortical
      atrophy and ventricular enlargement in all three patients, while other findings
      included thickening of the diploe in two patients and callosal atrophy, basal
      ganglia involvement, cerebellar changes and dilatation of venous sinuses in one
      patient. Although the combination of the above MRI findings is highly suggestive
      of a MPS, they carry a little predictive value in the different clinical stages
      of MPS IIIB.

PMID- 11578849
TI  - Relation between the date of cyst formation observable on ultrasonography and the
      timing of injury determined by serial electroencephalography in preterm infants
      with periventricular leukomalacia.
AB  - The aim of this study was to clarify the relation between the date of cyst
      formation and the timing of injury in preterm infants with periventricular
      leukomalacia in order to address the issue of whether or not we can determine the
      timing of injury on the basis of ultrasonographic findings. We studied 33 preterm
      infants with cystic periventricular leukomalacia, the gestational ages being 32
      weeks or less. As 27 of them exhibited either acute or chronic stage
      abnormalities in the initial electroencephalogram, the timing of injury was
      presumed to be before or around birth. For the remaining six infants, the timing
      of injury was considered to be postnatal in two infants, and was not determined
      in another four. The median date of cyst formation was 18 days of age (range, 10
      39 days) in the 27 infants with abnormal initial electroencephalograms. For these
      27 infants, the gestational age did not influence the date of cyst formation. In
      contrast, the date of cyst formation was significantly earlier in infants with
      widespread cysts than in those with localized cysts. In conclusion, it is
      difficult to determine the timing of injury from ultrasonographic findings,
      because the range of the date of cyst formation on ultrasonography was very wide
      among infants whose timing of injury was not greatly different.

PMID- 11578850
TI  - Body position-dependent changes in cerebral hemodynamics during apnea in preterm
      infants.
AB  - The objective of the present study was to evaluate sleeping position-dependent
      effects on cerebral hemodynamics during apnea in preterm infants. To this end,
      polygraphic studies were performed on 15 stable preterm infants lying prone and
      lying supine. Changes in cerebral blood volume (DeltaCBV) and in cerebral
      hemoglobin oxygenation ((Delta)cHbD) in association with apnea were measured by
      near infrared spectroscopy. For comparison, apnea in the prone position was
      matched for duration to apnea in the supine position. A total number of 98 pairs
      of apnea were compared. The mean duration of apnea was 8.2+/-3 s. In both
      positions there was a predominance of decrease in CBV and cHbD in association
      with apnea. The mean decrease of cHbD (-1.57+/-1.82 micromol/l) and of CBV (
      0.120+/-0.137 ml/100g brain) in the supine position was significantly pronounced
      compared to prone position (DeltacHbD: -1.18+/-1.77 micromol/l, DeltaCBV: 
      0.080+/-0.095 ml/100 g brain). The degree of DeltaCBV and DeltaHbD did not
      correlate with postconceptional or postnatal age (r2<0.01). In both positions
      there was a similar small decrease of SaO2 in association with apnea. In the
      supine position heart rate decreased slightly during apnea, whereas in the prone
      position no change in heart rate could be observed. The present study revealed a
      position-dependent different impact of apnea on cerebral hemodynamics. With
      regard to cerebral blood volume and oxygenation in association with apnea no
      negative effects of prone sleeping position could be observed in preterm infants.

PMID- 11578851
TI  - Clinical and electroencephalographic findings in early and late onset benign
      childhood epilepsy with occipital paroxysms.
AB  - Twenty-six patients were studied who had the clinical and electroencephalographic
      features of benign childhood epilepsy with occipital paroxysms (BCEOP) as defined
      by the Commission of the International League Against Epilepsy (ILAE). Twelve
      patients were characterized as having early-onset benign childhood occipital
      seizures (EBOS) susceptible syndrome, as described by Panayiotopoulos, and 14
      patients had late onset childhood idiopathic occipital seizures (LOS). Patients
      with symptomatic epilepsy and whose EEGs exhibited occipital spikes were
      excluded. The age of onset of the EBOS group ranged from 2.6 to 9.4 years (mean:
      4.9+/-1.7 years), which was significantly younger than the LOS group (range: 4-12
      years, mean:8.4+/-2.5 years). Both sexes were equally affected. The patients in
      the EBOS group had less frequent and longer seizures, ictal vomiting, more
      frequent deviation of the eyes, adversive seizures and more frequent nocturnal
      and secondary generalized seizures (P<0.05). By comparison, patients in the LOS
      group had a higher incidence of seizures, shorter duration of seizures and more
      frequent diurnal onset (P<0.01); also, although not statistically significant,
      the LOS group had more frequent visual hallucinations and headaches. The EEG
      topography in both groups showed at either side of occipital area typical
      paroxysms that were unilateral or bilaterally synchronous. Neither group had
      dipoles according to scalp voltage mapping. The clinical prognoses were favorable
      for both groups. To distinguish EBOS from LOS, detailed description of the age of
      onset, motor symptoms, visual symptoms, presence of eye deviation and diurnal or
      nocturnal occurrence are essential.

PMID- 11578852
TI  - Different effects between 7-nitroindazole and L-NAME on cerebral hemodynamics and
      hippocampal lesions during kainic acid-induced seizures in newborn rabbits.
AB  - We examined the effects of 7-nitroindazole (7-NI) and N-omega-nitro-L-arginine
      methyl ester (L-NAME) on the endogenous nitric oxide (NO) production in vivo,
      cerebral hemodynamics, and hippocampal lesions to investigate the different roles
      between endothelial NOS (eNOS) and neuronal NOS (nNOS) during kainic acid (KA)
      induced seizures in newborn rabbits. After a pre-treatment with 7-NI (50 mg/kg,
      i.p.), L-NAME (20 mg/kg, i.v.) or saline (1 ml, i.v.), KA (12 mg/kg, i.v.) was
      administered. NO production in the brain, regional cerebral blood flow (rCBF),
      cerebral oxygenation (concentrations of oxyhemoglobin (HbO2), deoxyhemoglobin
      (HbR), and total hemoglobin (tHb) in the brain tissue), and
      electroencephalography (EEG) were continuously monitored throughout the
      experiment lasting at least 60 min after the KA administration. There was a
      significant increase in NO generation in the brain during KA-induced seizures,
      which was inhibited by a pre-treatment with 7-NI or L-NAME. KA-induced seizures
      also increased rCBF significantly, which was inhibited not by 7-NI but by L-NAME.
      L-NAME pre-treatment caused a significant decrease in HbO2 and a significant
      increase in HbR during KA-induced seizures, compared with 7-NI and saline pre
      treatment. EEG abnormalities and Neuronal damages in the hippocampus were
      significantly lower in 7-NI- and L-NAME-treated animals respectively, than in
      saline-treated animals. The present data demonstrated that the selective nNOS
      inhibitor, 7-NI, attenuated neither rCBF nor cerebral oxygenation during the
      seizures, while the non-selective NOS (nNOS and eNOS) inhibitor, L-NAME,
      attenuated both. These findings suggest that NO, probably originating from eNOS,
      may play an important role in the cerebral circulation. Both 7-NI and L-NAME
      inhibited the NO production and EEG abnormalities during the seizures that led to
      less damage to the hippocampus.

PMID- 11578853
TI  - Sites and temporal changes of gangliosides GM1/GM2 storage in the Niemann-Pick
      disease type C mouse brain.
AB  - Niemann-Pick disease type C (NPC) is a progressive neurodegenerative disorder
      with characteristic storage of glycolipids in the brain. This study investigated
      cellular origin and temporal changes of monosialoganglioside storage in the
      Balb/c npc(nih) mouse brain by immunohistochemistry. Anti-GM1 gave positive
      staining of the hippocampus, thalamus, cerebellar molecular and Purkinje cell
      layers in the 3-week old NPC mouse brain and in general, the staining
      progressively diminished in an age-dependent manner. Anti-GM2 gave positive
      staining of the hippocampus, thalamus, cerebellar granule cell layer and
      brainstem nuclei in the 3-week old NPC mouse brain. In contrast to GM1, GM2
      staining in these regions, except for the hippocampus, progressively augmented in
      an age-dependent manner. Double labeling experiments with antibodies against
      glial fibrillary acidic protein and lysozyme showed localization of GM1 and GM2
      in reactive astrocytes and macrophages, respectively. Thus in the NPC mouse
      brain, GM1 accumulated primarily in neurons and astrocytes whereas GM2
      accumulated primarily in neurons and macrophages. Temporal profiles of storage
      were different from each other and depended on the cell type, presumably
      reflecting both developmental changes and progression of the disease process. We
      also investigated subcellular sites of storage in primary-cultured Purkinje cells
      from the neonatal NPC mouse by immunocytochemistry. In NPC Purkinje cells, GM1
      accumulated both in the cytoplasm and dendrites whereas GM2 showed punctuate
      accumulation in perinuclear vesicles. Thus, subcellular sites of storage were
      also different between GM1 and GM2 in NPC neurons.

PMID- 11578854
TI  - Empty sella in children as a key for diagnosis.
AB  - We performed magnetic resonance imaging of the pituitary gland in 354 children
      who were under the care of our pediatric neurological outpatient department.
      Among them, an empty sella was recognized in 11 children, who all showed normal
      hormonal results. The frequency of an empty sella was significantly high in
      idiopathic intracranial hypertension (4/4; P<0.0001) and nevoid basal cell
      carcinoma syndrome (3/5; P<0.0001). The ratio of an empty sella in children,
      excluding patients with idiopathic intracranial hypertension and nevoid basal
      cell carcinoma syndrome, is estimated to be 4/345 (1.2%), which is markedly lower
      than that in adults. Magnetic resonance imaging of the pituitary gland in
      children could provide important clues for the diagnosis of idiopathic
      intracranial hypertension or nevoid basal cell carcinoma syndrome.

PMID- 11578855
TI  - Plasmapheresis in fulminant acute disseminated encephalomyelitis.
AB  - We report an 11-year-old girl with acute disseminated encephalomyelitis (ADEM)
      who developed respiratory failure and coma despite the use of corticosteroid and
      intravenous immunoglobulin. We performed plasmapheresis four times, which
      improved her level of consciousness, hyperesthesia, external ophthalmoplegia and
      muscle weakness, and led to the normalization of brain and spinal cord MRI.
      Plasmapheresis might be an effective treatment in cases of fulminant ADEM.

PMID- 11578856
TI  - A case of early-onset benign occipital seizure susceptibility syndrome: decreased
      cerebral blood flow in the occipital region detected by interictal single photon
      emission computed tomography, corresponding to the epileptogenic focus.
AB  - Early-onset benign childhood occipital seizure susceptibility syndrome (EBOSS)
      recently described by Panayiotopoulos, is an early-onset variant of benign
      childhood epilepsy with occipital paroxysms. EBOSS is characterized by partial
      seizures that are predominantly manifested at night and associated with deviation
      of the eyes, vomiting and impairment of consciousness, but without ictal visual
      symptoms or postictal headache. The clinical features of our case were consistent
      with those of EBOSS, and we therefore diagnosed the patient as having a typical
      form of EBOSS. Neuroimaging by CT, MRI and MR angiography did not reveal a focal
      lesion. Interictal single photon emission computed tomography (SPECT) revealed
      decreased cerebral blood flow in the right occipital region corresponding to the
      epileptogenic focus shown on EEG. It remains unclear whether our finding on SPECT
      reflects secondary hypoperfusion due to minor morphological abnormality or
      immediate functional hypoperfusion. No reference to SPECT in a case of EBOSS has
      appeared in the literature to date. This report provides a better understanding
      of benign childhood epileptic syndromes with occipital spikes.

PMID- 11578857
TI  - The COE--Collier/Olf1/EBF--transcription factors: structural conservation and
      diversity of developmental functions.
AB  - One major conclusion of studies in Developmental Biology during the last two
      decades is that, despite profound anatomical differences, the building of
      vertebrate and arthropod bodies relies on the same fundamental molecular
      networks, including conserved cell signalling and transcription-regulatory
      cascades. Rodent Early B-Cell Factor/Olfactory-1 and Drosophila Collier belong to
      a recently defined, novel family of transcription factors, the Collier/Olf1/EBF
      (COE) proteins which have a unique DNA-binding domain. Early investigations
      revealed that, despite their high degree of sequence identity, the different
      vertebrate and invertebrate COE proteins play a variety of developmental roles.
      We review here the current evidence for this diversity of COE functions,
      including in the specification and differentiation of various neuronal
      populations. We also discuss the existence of an evolutionarily conserved pathway
      linking Notch signalling and COE regulatory functions in various developmental
      decisions.

PMID- 11578858
TI  - Diversification of cell types in the Drosophila eye by differential expression of
      prepattern genes.
AB  - According to Freeman (Development, 124 (1997) 261), reiterative use of Spitz
      signals emanating from already differentiated ommatidial cells triggers the
      differentiation of around ten different types of cells. Here we show evidence
      that the choice of cell fate by newly recruited ommatidial cells strictly depends
      on their developmental potential. Using forced expression of a constitutively
      active form of Ras1, three developmental potentials (rough, seven-up, and
      prospero expression) were visualized as relatively narrow bands corresponding to
      regions where rough-, seven-up- or prospero-expressing ommatidial cells would
      normally form. Ras1-dependent expression of ommatidial marker genes was regulated
      by a combinatorial expression of eye prepattern genes such as lozenge, dachshund,
      eyes absent, and cubitus interruptus, indicating that developmental potential
      formation is governed by region-specific prepattern gene expression.

PMID- 11578859
TI  - The role of vascular endothelial growth factor (VEGF) in vasculogenesis,
      angiogenesis, and hematopoiesis in zebrafish development.
AB  - Vascular endothelial growth factor (VEGF, VEGF-A), a selective mitogen for
      endothelial cells is a critical factor for vascular development. Two isoforms
      that differ in the presence of exons 6 and 7, Vegf(165) and Vegf(121), are the
      dominant forms expressed in zebrafish embryo. Simultaneous overexpression of both
      isoforms in the embryo results in increased production of flk1, tie1, scl, and
      gata1 transcripts, indicating a stimulation of both endothelial and hematopoietic
      lineages. We also demonstrate that vegf can stimulate hematopoiesis in zebrafish
      by promoting the formation of terminally differentiated red blood cells.
      Simultaneous overexpression of both isoforms also causes ectopic vasculature and
      blood cells in many of the injected embryos as well as pericardial edema in later
      stage embryos. Overexpression of vegf also resulted in earlier onset of flk1,
      tie1, scl, and gata1 expression in the embryo, indicating a possible role of vegf
      in stimulating the differentiation of both vascular and hematopoietic lineages.
      Co-injection of RNAs for both isoforms results in increased expression of three
      of these markers over and above that observed when either RNA is singly injected
      and analysis of vegf expression in the notochord mutants no tail and floating
      head suggests that the notochord patterns the formation of the dorsal aorta by
      stimulating adjacent somite cells to express vegf, which in turn functions as a
      signal in dorsal aorta patterning. Finally, studies of vegf expression in cloche
      mutant indicate that vegf expression is generally independent of cloche function.
      These results show that in the zebrafish embryo, vegf can not only stimulate
      endothelial cell differentiation but also hematopoiesis. Moreover, these effects
      are most dramatic when both vegf isoforms are co-expressed, indicating a
      synergistic effect of the expression of the two forms of the VEGF protein.

PMID- 11578860
TI  - Cell type specific expression of vascular endothelial growth factor and
      angiopoietin-1 and -2 suggests an important role of astrocytes in cerebellar
      vascularization.
AB  - The vascularization of the central nervous system occurs by angiogenic sprouting,
      a process in which different factors like vascular endothelial growth factor
      (VEGF) and angiopoietin (Ang)-1/2 must act in a coordinated fashion. We
      investigated how these factors participate in capillarization of the cerebellum,
      an area experiencing marked reorganization processes during its postnatal
      development. VEGF and Ang-1 mRNA were predominantly expressed by astrocytes,
      while Ang-2 mRNA was specifically induced at the tip of invading endothelial cell
      cords. Similar to the cerebral cortex, vascularization of the cerebellum occurred
      in an inside-out pattern, following closely the generation and differentiation of
      each cerebellar layer. VEGF and Ang-1/2 expression patterns shifted in a similar
      inside-out fashion, supporting their proposed function in vessel growth and
      maturation.

PMID- 11578861
TI  - Transcriptional regulation of Mesp1 and Mesp2 genes: differential usage of
      enhancers during development.
AB  - Mesp1 and Mesp2 encode bHLH-type transcription factors, Mesp1 and Mesp2,
      respectively. The expression of both genes is observed in the nascent mesoderm,
      and subsequently in the rostral presomitic mesoderm. To determine the regulatory
      mechanism for gene expression, we attempted to identify enhancer elements by
      transient transgenic analysis. At least two enhancers, which are responsible for
      the expression of the two genes in the early mesoderm (early mesodermal enhancer,
      EME) and the presomitic mesoderm (PSM enhancer, PSME), and one suppressor, which
      is responsible for the rostrally restricted expression in the presomitic
      mesoderm, were identified. Deletion studies of these enhancer elements indicate
      that either gene may use the same enhancer for early mesoderm development,
      whereas both genes may utilize separate enhancers to regulate their expression in
      the presomitic mesoderm.

PMID- 11578862
TI  - Siamois functions in the early blastula to induce Spemann's organiser.
AB  - In Xenopus, the Spemann organiser is defined as a dorsal territory in the early
      gastrula that initiates development of the embryonic axis. It has been shown that
      the early zygotic transcription factor Siamois is essential for Spemann's
      organiser formation. By the onset of gastrulation, the organiser is patterned
      into a vegetal head organiser, which induces anterior structures upon
      transplantation, and a more animal trunk organiser, which induces a posterior
      neuraxis. However, it is unclear when these distinct organiser domains are
      initially specified. To shed light on this question, we analysed the temporal
      activity of Siamois, as this factor induces both head and trunk development, when
      ectopically expressed via mRNA injection. In this study, we expressed Siamois
      ectopically at different time points and analysed the extent of axial
      development. Using a hormone-inducible version of Siamois, we found evidence for
      a tight window of competence during which ventral cells can respond to Siamois by
      commencing both the head and the trunk genetic programmes. The competence to form
      Spemann's organiser was lost 2 h before gastrulation, although partial axis
      formation could still occur following delayed activation of Siamois. We
      demonstrate that this late response to Siamois involves a new role for this gene,
      which can indirectly repress ventral gene expression, in the absence of known
      organiser genes.

PMID- 11578863
TI  - A common cis-acting sequence in the DiGeorge critical region regulates bi
      directional transcription of UFD1L and CDC45L.
AB  - Two to three megabase deletions on chromosome 22q11 are the cytogenetic findings
      most commonly associated with cardiac and craniofacial defects in humans. The
      constellation of clinical findings associated with these deletions is termed the
      22q11 deletion syndrome. We had earlier described a patient with the 22q11
      deletion phenotype who was hemizygous for an atypical 20 kb microdeletion in this
      region. The deletion included coding regions of two genes organized head-to-head,
      UFD1L and CDC45L, along with an 884 bp CpG-rich intervening region. Based on this
      genomic organization, we hypothesized that both genes may be co-expressed and co
      regulated by sequences within this region. We demonstrate that expression of both
      genes is enhanced in a similar pattern in precursors of structures affected by
      the deletion. The intergenic region is sufficient to direct transcription most
      strongly in the developing pharyngeal arches and limb buds of transgenic mice and
      can also direct bi-directional transcriptional activation in a neural crest
      derived cell line. Deletion analyses revealed that a 404 bp fragment closest to
      UFD1L is necessary and sufficient to direct this bi-directional transcriptional
      activity. These results reveal the presence of a conserved regulatory region in
      the 22q11 deletion locus that can direct simultaneous transcription of genes
      involved in ubiquitin mediated protein processing (UFD1L) and cell cycle control
      (CDC45L).

PMID- 11578864
TI  - Dpp and Hedgehog mediate neuron-glia interactions in Drosophila eye development
      by promoting the proliferation and motility of subretinal glia.
AB  - Neuron-glia interactions are crucial for the establishment of normal connectivity
      in the nervous system during development, but the molecular signals involved in
      these interactions are largely unknown. Here we show that differentiating
      photoreceptors in the developing Drosophila eye influence the proliferative and
      migratory behavior of the subretinal glia through the diffusible factors
      Decapentaplegic (Dpp) and Hedgehog (Hh). We demonstrate that proliferation and
      migration of the glia are separable processes, and that Dpp promotes both the
      proliferation and motility of the glia, whereas Hh appears to promote only their
      motility; neither specifies the direction of migration. We present evidence that
      Dpp and Hh act on the glia in parallel and through the regulation of
      transcription. Finally, we show that ectopic migration of subretinal glia can
      result in the ectopic projection of photoreceptor axons. Our study suggests a
      novel function for Hh in regulating migratory behavior and provides further
      evidence for a complex mutual dependence between glial and neuronal cells during
      development.

PMID- 11578865
TI  - A GATA-6 gene heart-region-specific enhancer provides a novel means to mark and
      probe a discrete component of the mouse cardiac conduction system.
AB  - The transcriptional programs that specify the distinct components of the cardiac
      conduction system are poorly understood, in part due to a paucity of definitive
      molecular markers. In the present study we show that a cGATA-6 gene enhancer can
      be used to selectively express transgenes in the atrioventricular (AV) conduction
      system as it becomes manifest in the developing multichambered mouse heart.
      Furthermore, our analysis of staged cGATA-6/lacZ embryos revealed that the
      activity of this heart-region-specific enhancer can be traced back essentially to
      the outset of the cardiogenic program. We provide evidence that this enhancer
      reads medial/lateral and anterior/posterior positional information before the
      heart tube forms and we show that the activity of this enhancer becomes
      restricted at the heart looping stage to AV myocardial cells that induce
      endocardial cushion formation. We infer that a deeply-rooted heart-region
      specific transcriptional program serves to coordinate AV valve placement and AV
      conduction system formation. Lastly, we show that cGATA-6/Cre mice can be used to
      delete floxed genes in the respective subsets of specialized heart cells.

PMID- 11578866
TI  - Two mouse piwi-related genes: miwi and mili.
AB  - Genes belonging to the piwi family are required for stem cell self-renewal in
      diverse organisms. We cloned mouse homologues of piwi by RT-PCR using
      degenerative primers. The deduced amino acid sequences of mouse homologues MIWI
      and MILI showed that each contains a well-conserved C-terminal PIWI domain and
      that each shares significant homology with PIWI and their human counterparts
      HIWI. Both miwi and mili were found in germ cells of adult testis by in situ
      hybridization, suggesting that these genes may function in spermatogenesis.
      Furthermore, mili was expressed in primordial germ cells (PGCs) of developing
      mouse embryos and may therefore play a role during germ cell formation. MIWI may
      be involved in RNA processing or translational regulation, since MIWI was found
      to possess RNA binding activity. Our data suggest that miwi and mili regulate
      spermatogenesis and primordial germ cell production.

PMID- 11578867
TI  - Different levels of Hoxa2 are required for particular developmental processes.
AB  - Hoxa2 is required for a variety of developmental processes in the branchial
      arches and in the hindbrain. We have created a Hoxa2 allele that is about 45% as
      active in transcription as its wild-type counterpart. This allele, together with
      the Hoxa2 null and wild-type alleles, allowed the generation of embryos
      developing in the presence of different levels of Hoxa2 activity. Analysis of
      these embryos indicates that in general the hindbrain is more resistant to Hoxa2
      deficiencies than the second branchial arch. Also, within the second arch,
      proximo-caudal areas are more sensitive than the rostro-distal. In the hindbrain,
      basic segmentation and patterning processes seem to occur normally at Hoxa2
      levels as low as 20% of the normal. In addition, specific neuronal markers along
      the dorso-ventral axis of the hindbrain seem differentially affected by reduced
      Hoxa2 levels. These results provide new clues to understand the role of Hoxa2 in
      the different embryonic areas where it is required.

PMID- 11578868
TI  - BMP growth factors and Phox2 transcription factors can induce synaptotagmin I and
      neurexin I during sympathetic neuron development.
AB  - Synaptotagmin I and neurexin I mRNAs, coding for proteins involved in
      neurotransmitter secretion, become detectable in primary sympathetic ganglia
      shortly after initial induction of the noradrenergic transmitter phenotype. To
      test whether the induction of these more general neuronal genes is mediated by
      signals known to initiate noradrenergic differentiation in a neuronal
      subpopulation, we examined their expression in noradrenergic neurons induced by
      ectopic overexpression of growth and transcription factors. Overexpression of
      BMP4 or Phox2a in vivo results in synaptotagmin I and neurexin I expression in
      ectopically located noradrenergic cells. In vitro, BMP4 initiates synaptotagmin I
      and neurexin I expression in addition to tyrosine hydroxylase induction. Thus,
      the induction of synaptotagmin I and neurexin I, which are expressed in a large
      number of different neuron populations, can be accomplished by growth and
      transcription factors available only to a subset of neurons. These findings
      suggest that the initial expression of proteins involved in neurotransmitter
      secretion is regulated by different signals in different neuron populations.

PMID- 11578869
TI  - Vascular expression of Notch pathway receptors and ligands is restricted to
      arterial vessels.
AB  - Mice with targeted mutations in genes required for Notch signal transduction die
      during embryogenesis, displaying overt signs of hemorrhage due to defects in
      their vascular development. Surprisingly, directed expression of a constitutively
      active form of Notch4 within mouse endothelial cells produces a similar vascular
      embryonic lethality. Moreover, patients with mutations in Notch3 exhibit the
      cerebral vascular disorder, cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL). These findings underscore
      the importance of Notch signaling in vascular development; however, they do not
      identify the specific functional defect. Here, we report that Notch1, Notch3,
      Notch4, Delta4, Jagged1 and Jagged2 are all expressed in arteries, but are not
      expressed by veins. These findings identify an aspect of Notch signaling that
      could contribute to the mechanism by which this pathway modulates vascular
      morphogenesis.

PMID- 11578870
TI  - Identification and localization of M-CoREST (1A13), a mouse homologue of the
      human transcriptional co-repressor CoREST, in the developing mouse CNS.
AB  - By means of subtractive and differential hybridization techniques we have
      identified a novel murine gene (1A13) the expression of which is developmentally
      regulated in the mouse brain. Comparison of the nucleotide and predicted protein
      sequence revealed closest relationship of 1A13 to human CoREST, a transcriptional
      co-repressor required for regulation of neural-specific gene expression. Thus, we
      will refer to 1A13 as M-CoREST. As shown by in situ hybridization and Northern
      blotting, expression of M-CoREST mRNA is abundant in neural tissue at early
      embryonic stages but declines significantly towards birth, coincident with the
      progression of CNS maturation.

PMID- 11578871
TI  - Identification and characterization of the Drosophila tau homolog.
AB  - A pathological hallmark of neurodegenerative tauopathies, including Alzheimer's
      disease and a group of clinically heterogeneous frontotemporal dementias, is the
      presence of intracellular neurofibrillary protein lesions (reviewed in
      Spillantini and Goedert, TINS 10 (1998) 428). The principal component of these
      structures is the microtubule-associated protein tau. Although tau is normally a
      highly soluble protein enriched in axons, in these deposits, it is abnormally
      hyperphosphorylated, insoluble, and redistributed to the somatodendritic
      compartments of neurons. Through ultrastructual analyses, it has been determined
      that the tau protein in these lesions is filamentous and organized into paired
      helical filaments, straight filaments, or ribbon-like filaments (Goedert et al.,
      The Molecular and Genetic Basis of Neurological Disease (1997) 613). By the
      dynamic binding of microtubules, tau is thought to promote the structural
      stability of axons, but whether tau aggregates contribute to neurodegeneration
      through a direct toxicity on normal cellular functions such as organelle
      transport or an indirect effect on microtubule stability, is currently unknown.
      The identification of mutations in the tau locus in patients with familial
      frontotemporal dementia and Parkinsonism linked to chromosome 17 has demonstrated
      that mutations in tau are sufficient to cause neurodegenerative disease (Poorkaj
      et al., Ann. Neurol. 43 (1998) 815; Hutton et al., Nature 393 (1998) 702). To
      elucidate the mechanisms by which tau dysfunction contributes to neuronal loss,
      we have sought to model human tauopathies in a genetically tractable organism.
      Here we describe the isolation of a Drosophila tau cDNA (GenBank accession number
      AY032977), the production of antibodies that recognize the encoded protein, and
      their use in determining the expression and subcellular localization of the fly
      tau protein.

PMID- 11578872
TI  - Expression of BMP signalling pathway members in the developing zebrafish inner
      ear and lateral line.
AB  - In this paper we describe the mRNA expression patterns of members of the bone
      morphogenetic protein (BMP) signalling pathway in the developing zebrafish ear.
      bmp2b, 4, and 7 are expressed in discrete areas of otic epithelium, some of which
      correspond to sensory patches. bmp2b and 4 mark the developing cristae before and
      during the appearance of differentiated hair cells. bmp4 is also expressed in a
      dorsal, non-sensory region of the ear. Expression of bmps in cristae is conserved
      between zebrafish, chick, and mouse, but there are also notable differences in
      ear expression patterns between these species. Of five zebrafish BMP antagonists,
      only one (follistatin) shows significant expression in the otic epithelium. The
      type I receptor bmpr-IB shows localised expression in the ear epithelium.
      Mediators of BMP signalling, smad1 and smad5, are expressed in statoacoustic and
      lateral line ganglia; smad5 is also expressed at low levels throughout the ear
      epithelium. An inhibitory smad, smad6, is expressed laterally in the ear
      epithelium. Lateral line primordia and neuromasts also express bmp2b, 4,
      follistatin, smad1, and smad5. The conservation of bmp expression in cristae
      among different species adds weight to the growing evidence that BMPs are
      required for the development of the vertebrate ear.

PMID- 11578873
TI  - Differential expression of two scribble isoforms during Drosophila embryogenesis.
AB  - The tumour suppressor gene scribble (scrib) is required for epithelial polarity
      and growth control in Drosophila. Here, we report the identification and
      embryonic expression pattern of two Scrib protein isoforms resulting from
      alternative splicing during scrib transcription. Both proteins are first
      ubiquitously expressed during early embryogenesis. Then, during morphogenesis
      each Scrib protein displays a specific pattern of expression in the central and
      peripheral nervous systems, CNS and PNS, respectively. During germ band
      extension, the expression of the longer form Scrib1 occurs predominantly in the
      neuroblasts derived from the neuro-ectoderm and becomes later restricted to CNS
      neurones as well as to the pole cells in the gonads. By contrast, the shorter
      form Scrib2 is strongly expressed in the PNS and a subset of CNS neurones.

PMID- 11578874
TI  - Expression patterns of the Ets transcription factors from the PEA3 group during
      early stages of mouse development.
AB  - erm, er81 and pea3 are three related genes that define a novel Ets-related
      subfamily of transcription factors. The expression patterns of these genes has
      been previously characterized in the mouse from embryonic day (E) 9.5 to birth
      (Oncogene 15 (1997) 937). In this study, we report differential expression
      patterns of the PEA3 group genes during early mouse post-implantation
      development. erm and pea3 expression patterns were partly overlapping. erm was
      activated prior to pea3 in the distal tip of the embryonic epiblast but, at
      primitive streak-stages, both genes were coexpressed in the posterior region of
      the embryo in epiblast, primitive streak and adjacent mesoderm. Similar erm and
      pea3 expression patterns were seen later in posterior neural plate, presomitic
      and lateral mesoderm, mesonephros, and tail bud. Only erm, however, was expressed
      in specific brain regions corresponding to prospective midbrain and ventral
      forebrain. erm was also strongly expressed as early as E8 in the developing
      branchial region, especially at the level of branchial pouches, whereas pea3
      transcripts appeared later in frontonasal and first arch mesenchyme. er81
      transcripts were not detected prior to E9.0-9.5, suggesting that this gene may
      not be involved in early developmental events.

PMID- 11578875
TI  - Expression pattern of DMAP-85 during Drosophila embryonic development.
AB  - Microtubule-associated proteins (MAPs) play major regulatory roles on the
      organization and integrity of the cytoskeletal network. Previously, we identified
      DMAP-85, a Drosophila MAP that promotes tubulin polymerization in vitro. In this
      work, we examine the distribution of DMAP-85 and its association pattern with
      microtubules at embryonic stages. Immunoblots revealed that DMAP-85 was present
      throughout embryogenesis, but it was most abundant in stages 6-9.
      Immunofluorescence studies showed that DMAP-85 was associated with sub
      populations of stable microtubules during embryo cellularization, and after
      gastrulation with interphase microtubule arrays. At late embryonic stages, it was
      preferentially found in the ventral nerve cord, co-localizing with axonal
      microtubules. These observations are in agreement with previous reports on DMAP
      85 functions, suggesting that DMAP-85 might be required for the stabilization and
      organization of cytoplasmic microtubules during embryonic development.

PMID- 11578876
TI  - Fgf8 transcripts are located in tendons during embryonic chick limb development.
AB  - Fibroblast growth factor 8 (Fgf8) is a secreted growth factor involved in the
      initiation, outgrowth and patterning of vertebrate limbs (Genes Dev. 12 (1998)
      1571). In this paper, we present a new site of expression of Fgf8 in the chick
      limb. Fgf8 transcripts are localised close to the muscle fibres, at the same
      level as the tendon-associated molecules, tenascin and scleraxis. Fgf8 is
      expressed in a sub-region of the tendons during limb development; its location
      being restricted to the area near the muscle. In addition, the restricted Fgf8
      expression in the tendons allowed us to observe that the myogenic determination
      factor (MyoD) is not detected at the myotendinous junction.

PMID- 11578877
TI  - Expression pattern of Zac1 mouse gene, a new zinc-finger protein that regulates
      apoptosis and cellular cycle arrest, in both adult brain and along development.
AB  - Using in situ hybridization, we analyzed the expression pattern of the Zac1 gene
      in mouse brain during the embryonic and postnatal development. Zac1 is a new gene
      that regulates extensive apoptosis and cell cycle arrest through unrelated
      pathways. At embryonic stages, strong expression was observed in brain areas with
      active proliferation (ventricular zone and numerous neuroepithelius) and in
      nervous system (neural retina and neural tube). In addition, some areas with
      differentiation activity were noticeably labeled such as arcuate nucleus and
      amygdaloid region of the brain together with other embryonic sites (hindlimb,
      forelimb and somites). From P0 onwards, the expression appeared in some
      proliferative areas, such as subventricular zone and cerebellum (external
      granular layer and Purkinje cells) and in some synaptic plasticity areas, such as
      the dorso and ventromedial hypothalamic nuclei, arcuate nucleus, ventral thalamic
      nucleus.

PMID- 11578878
TI  - A novel member of the RBCC family, Trif, expressed specifically in the spermatids
      of mouse testis.
AB  - Members of the RING finger family are implicated in a variety of functions such
      as signal transduction, transcriptional regulation and other developmental
      processes. Using degenerate oligonucleotide primers corresponding to the RING
      domain, we isolated a novel RING finger gene from the mouse testis cDNA library,
      which was about 1.8 kb and was termed Trif (testis-specific ring finger). This
      deduced protein contains an N-terminal RING-finger, a B-box, and a C-terminal B
      30.2-like domain, which make the Trif protein a member of the RING finger-B-box
      coil-coil family. Northern blot analysis of adult multiple tissues indicated that
      Trif is expressed predominantly in the testis. Further analysis detected Trif
      transcripts in the testis from day 20 of the postnatal stage. In situ
      hybridization indicated that Trif is expressed in the round spermatids of the
      seminiferous tubules. These expression data suggest that Trif may play an
      important role in the regulation of spermatogenesis.

PMID- 11578879
TI  - Connexin43 expression during Xenopus development.
AB  - The spatio-temporal expression of connexin43 in Xenopus laevis embryos was
      studied by in situ hybridization. Cx43 expression is first detected at stage 25
      in the developing eye. In stage 32, expression was found in the margin of the
      lens placode, the cement gland, notochord, and in stage 37 in the branchial
      arches. Early limb buds show strong expression of Cx43 distally while later on
      expression is confined to sites of precartilage condensation.

PMID- 11578880
TI  - Expression of MUL, a gene encoding a novel RBCC family ring-finger protein, in
      human and mouse embryogenesis.
AB  - We studied the expression of MUL, a gene encoding a novel member of the RING-B
      Box-Coiled Coil family of zinc finger proteins that underlies the human inherited
      disorder, Mulibrey nanism. In early human and mouse embryogenesis MUL is
      expressed in dorsal root and trigeminal ganglia, liver and in epithelia of
      multiple tissues.

PMID- 11578881
TI  - Molecular cloning and embryonic expression of the Xenopus Arnt gene.
AB  - In this paper, we report the cloning of a Xenopus bHLH/PAS factor homologous to
      the mammalian aryl hydrocarbon receptor nuclear translocator (Arnt) or Drosophila
      Tango gene. Sequence data analysis indicates that protein domains organization in
      xArnt is strongly conserved and that xArnt is highly related to the mammalian
      Arnt1 isoform. As revealed by reverse transcriptase polymerase chain reaction and
      whole-mount in situ hybridization, xArnt gene is expressed during early and late
      development. At early stages, xArnt transcripts are restricted to the ectoderm
      and extends to the marginal zone at gastrula stage. In tail bud embryo, xArnt is
      strongly expressed in branchial arches, optical and optical vesicles, and
      pronephros and pronephritic duct.

PMID- 11578882
TI  - Does functional ability in the postoperative period differ between remifentanil-
      and fentanyl-based anesthesia?
AB  - STUDY OBJECTIVES: To compare patients' functional ability in the 24-hour
      postoperative period following a remifentanil compared to a hypnotic-fentanyl
      treated anesthesia regimen using a 24-Hour Functional Ability Questionnaire.
      DESIGN: Prospective, 1:1 single-blind, randomized, controlled effectiveness
      study. SETTING: Multicenter study including 156 hospitals and ambulatory surgery
      facilities. PATIENTS: 2438 patients (1496 outpatients and 942 inpatients) 18
      years of age or older, scheduled for elective surgeries under general
      endotracheal anesthesia, with an expected duration of unconsciousness of > or =30
      minutes. INTERVENTIONS: Patients were randomized to receive either intravenous
      remifentanil (0.5 microg/kg/min for induction and intubation; with the infusion
      rate decreased to 0.25 microg/kg/min after intubation) or fentanyl (administered
      according to anesthesiologists' usual practice) as the opioid during surgery.
      Concomitant hypnotic drugs were propofol and/or isoflurane (with or without
      nitrous oxide) titrated according to protocol. Transition analgesia with either
      morphine or fentanyl was given in the remifentanil patients and at the discretion
      of the anesthesiologists in the fentanyl patients. MEASUREMENTS: A validated set
      of measurements of functional ability, rather than more traditional clinical
      psychological methods, to compare the recovery of patients from remifentanil- and
      fentanyl-treated anesthetic regimens up to 24 hours after surgery. MAIN RESULTS:
      Remifentanil was statistically superior to fentanyl for the four functional
      assessments evaluated: walking without dizziness, thinking clearly,
      concentration, and communicating effectively. These differences reflect events
      occurring within the first 24 hours after anesthesia and surgery. CONCLUSIONS: A
      remifentanil-treated anesthetic demonstrated earlier return to some functions
      than a fentanyl-treated technique. Although functional assessment is a field that
      is still in its infancy, a questionnaire to assess functional ability during the
      24 hours after anesthesia may provide more practical information about anesthetic
      recovery than previously used, traditional psychomotor evaluations.

PMID- 11578883
TI  - Hemodynamics and emergence profile of remifentanil versus fentanyl prospectively
      compared in a large population of surgical patients.
AB  - STUDY OBJECTIVE: To compare the responses to, and hemodynamics associated with
      surgical stress, recovery profiles, and anesthesiologists' satisfaction following
      balanced general anesthesia using either remifentanil or fentanyl in a large
      scale population. DESIGN: Prospective, 1:1 single blind, randomized, controlled
      effectiveness study in which patients received either remifentanil or fentanyl in
      combination with a hypnotic-based anesthesia regimen of either isoflurane or
      propofol. SETTING: Multicenter study including 156 hospitals and ambulatory
      surgery facilities. PATIENTS: 2,438 patients (1,496 outpatients and 942
      inpatients), 18 years of age or older, scheduled for elective surgeries under
      general endotracheal anesthesia, with an expected duration of unconsciousness >
      or =30 minutes. INTERVENTIONS: Patients were randomized to receive either
      intravenous (IV) remifentanil (0.5 microg/kg/min for induction and intubation,
      with the infusion rate decreased to 0.25 microg/kg/min after intubation) or IV
      fentanyl (administered according to anesthesiologists' usual practice) as the
      opioid during surgery. Concomitant hypnotic drugs were either propofol and/or
      isoflurane (with or without nitrous oxide) titrated according to protocol.
      Transition analgesia with either morphine or fentanyl was given to the
      remifentanil patients and, at the anesthesiologists' discretion, in the fentanyl
      patients. MEASUREMENTS: Vital signs, adverse events, and emergence profiles were
      assessed and recorded. Recovery profile was assessed by recording time spent in
      the postanesthesia care unit and step-down recovery unit, number and timing of
      adverse events, timing and dosage of rescue medications, and time to eligibility
      for discharge (to home or to hospital room). Anesthesiologists' satisfaction with
      the anesthetic regimen was assessed at the end of surgery. MAIN RESULTS:
      Remifentanil-treated patients exhibited lower systolic and diastolic blood
      pressures (by 10-15 mmHg) and lower heart rates (by 10-15 bpm) intraoperatively
      compared to the fentanyl-treated patients. This difference promptly disappeared
      on emergence. Remifentanil-treated patients responded to verbal command, left the
      operating room, and (for outpatients) were discharged home sooner than fentanyl
      treated patients. Anesthesiologists rated the predictability of response to
      intraoperative titration, assessment of hemodynamic profiles, and the quality of
      anesthesia higher in the remifentanil-treated patients. CONCLUSIONS: This study
      confirms previous observations on the hemodynamic properties associated with
      remifentanil and extends these to a wider context than previously reported. These
      characteristics provide clinicians with an alternative in opioid-based
      anesthesia.

PMID- 11578884
TI  - Effects of small doses of prostaglandin E(1) on systemic hemodynamics and jugular
      venous oxygen saturation during cardiopulmonary bypass.
AB  - STUDY OBJECTIVE: To examine the effects of small doses of prostaglandin E(1)
      (PGE(1)) on systemic hemodynamics and cerebral oxygenation during cardiopulmonary
      bypass(CPB). DESIGN: Randomized, prospective study. SETTING: Cardiac surgery at
      Saitama Cardiovascular and Pulmonary Center. PATIENTS: Forty patients who
      underwent elective coronary artery bypass surgery. INTERVENTIONS: The study was
      performed at the stable CPB period. Patients were randomly divided into four
      groups: control group (n = 10) received an infusion of saline, PGE(1) 10 group (n
      = 10) received an infusion of PGE(1) 10 ng/kg/min, PGE(1) 25 group (n = 10)
      received an infusion of PGE(1) 25 ng/kg/min, and the PGE(1) 50 group (n = 10)
      received an infusion of PGE(1) 50 ng/kg/min. MEASUREMENTS: After measuring the
      baseline partial pressure of the arterial oxygen saturation (SpO(2)), mixed
      venous oxygen saturation (SvO(2)), and jugular venous oxygen saturation
      (SjvO(2)), blood gases, and cardiovascular hemodynamic values, PGE(1) was infused
      intravenously at rate of between 10 and 50 ng/kg/min. PGE(1) infusion continued
      30 minutes after the start of drug infusion, and the blood gas analysis and
      cardiovascular hemodynamic values were simultaneously determined together with
      the hemodynamic values at 2, 5, 10, 20, and 30 minutes during drug infusion. At
      30 minutes after discontinuation of the drug infusion, the blood gas analyses
      were simultaneously determined together with the hemodynamic values. MAIN
      RESULTS: Mean arterial pressure (MAP) in PGE(1) 25 and 50 groups was decreased 20
      and 30 minutes after the start of PGE(1) infusion compared with the baseline
      value (p < 0.05). In contrast, SvOm(2) in PGE(1) 25 and 50 groups was increased
      20 and 30 minutes after the start of PGE(1) infusion compared with the baseline
      value (p < 0.05). There was no change in SjO(2) value despite a decrease in MAP
      during the study. CONCLUSIONS: Cerebral oxygenation estimated by SjvO(2) was
      maintained despite a decrease in MAP during the administration rate of PGE(1)
      between 10 and 50 ng/kg/min.

PMID- 11578885
TI  - A comparison of propofol and remifentanil for sedation and limitation of movement
      during periretrobulbar block.
AB  - STUDY OBJECTIVES: To compare clinical conditions in patients sedated with
      propofol or remifentanil during combined peri-bulbar and retrobulbar block (PRBB)
      for cataract surgery. DESIGN: Prospective, randomized, double-blind study.
      SETTING: Private clinic. PATIENTS: 106 ASA physical status I and II patients
      scheduled for cataract surgery. INTERVENTIONS: Patients were randomized to
      receive either 0.5 mg/kg propofol (Group P) or 0.3 microg/kg remifentanil (Group
      R) as an intravenous (IV) bolus 1 minute prior to PRBB. At the same time,
      patients in both groups also received 0.5 to 1 mg midazolam IV. Movement of the
      hands, arms, head, and eyes were counted during each stage of the procedure by an
      observer who was blinded to the sedation used. Heart rate (HR), blood pressure
      (BP), respiratory rate (RR), expiratory CO(2) (PECO(2)), and hemoglobin oxygen
      saturation (SaO(2)) were recorded every minute for 10 minutes after the PRBB.
      Anesthetic complications, recall, and the pain experienced with the block and
      surgery were compared between the two groups. Means and variance of the results
      were compared with one-way analysis of variance and Fisher's exact test.
      MEASUREMENTS AND MAIN RESULTS: Movements of the hands, arms, and head were
      significantly greater in Group P during all stages of the block. Almost no
      movements were recorded in the remifentanil group. Immediately after the PRBB (1
      to 6 min), HRs were higher in Group P (73 +/- 11 bpm vs. 67 +/- 10 bpm; p =
      0.0075), whereas the RRs were slower in Group R for the period 1 to 5 minutes
      after the PRBB (16 +/- 5 breaths/min vs.14 +/- 4 breaths/min; p = 0.0206). At
      these times, the mean PECO(2) was higher in Group R (36 +/- 7 mmHgvs. 32 +/- 9
      mmHg; p = 0.0125). Nineteen patients in the propofol group sneezed during the
      medial peribulbar injection compared with none in the remifentanil group.
      Anesthetic and surgical complications were unremarkable and similar for the two
      groups. CONCLUSIONS: Respiratory depression with remifentanil was mild and not
      clinically significant. Remifentanil sedation for this application was superior
      to sedation with propofol.

PMID- 11578886
TI  - Tracheal intubation through the laryngeal mask airway using a gum elastic bougie:
      the effect of head position.
AB  - STUDY OBJECTIVE: To determine the effect of head position on success of tracheal
      intubation through a Laryngeal Mask Airway (LMA) using a gum elastic bougie.
      DESIGN: Randomized, controlled study. SETTING: Anesthesia and operating rooms of
      the University Hospital, Nottingham, UK. PATIENTS: 20 patients scheduled to
      undergo routine elective surgery requiring the use of an LMA for anesthesia.
      INTERVENTIONS: Blind placement of a gum elastic bougie through an LMA in two head
      positions. MEASUREMENTS AND MAIN RESULTS: Final position of the gum elastic
      bougie after removal of the LMA as determined by fiberoptic laryngoscopy. The gum
      elastic bougie was correctly sited in the trachea in the classical intubating
      position in 4/20 (20%) and in the neutral position in 0/20 (0%). There was no
      difference in the success of this technique between the two head positions.
      CONCLUSIONS: This technique cannot be recommended as an alternative to direct
      laryngoscopy following a failed intubation.

PMID- 11578887
TI  - Comparing the efficacy of prophylactic metoclopramide, ondansetron, and placebo
      in cesarean section patients given epidural anesthesia.
AB  - STUDY OBJECTIVE: To compare the relative efficacy of prophylactic metoclopramide,
      ondansetron, and placebo in nonemergent cesarean section patients given epidural
      anesthesia intraoperatively and for the first 24-hour period after delivery.
      DESIGN: Randomized, double blind, placebo-controlled study. SETTING: Inpatient
      obstetric unit at a university hospital center. PATIENTS: 164 nonemergent
      cesarean section patients given epidural anesthesia. INTERVENTION: At time of
      umbilical cord clamp, patients received intravenously (IV) either 4 mg
      ondansetron (Group O) or 10 mg metoclopramide (Group M) or 10 mL normal saline
      (Group P). MEASUREMENTS AND MAIN RESULTS: Episodes and severity of nausea and
      vomiting, rescue antiemetic requirement, patient satisfaction, and side effects
      were recorded. The frequency of intraoperative nausea were 24%, 43%, and 57% for
      Group O, Group M, and Group P, respectively (p < 0.03). The frequency of nausea
      for the 24-hour study period were 26%, 51% and 71% for Groups O, M, and P
      respectively (p < 0.03). The frequency of intraoperative and postoperative
      vomiting were similar between Group O and Group M, but significantly higher in
      Group P (p < 0.05). Overall patient satisfaction was highest in Group O compared
      with Groups P and M (p < 0.05). Maximum analog sedation score was higher in Group
      M compared to Groups O and P (p < 0.05). CONCLUSIONS: In cesarean section
      patients given epidural anesthesia, prophylactic ondansetron, 4 mg IV, is more
      efficacious and has a higher patient satisfaction than that with metoclopramide,
      10 mg IV, or placebo in preventing nausea and achieving complete responses during
      intraoperative period and the first 24-hour postdelivery period. However, there
      is no difference between ondansetron and metoclopramide in reducing frequency of
      vomiting. Prophylactic ondansetron 4 mg IV is more effective in preventing nausea
      than vomiting.

PMID- 11578888
TI  - Pressure controlled versus volume controlled ventilation with laryngeal mask
      airway.
AB  - STUDY OBJECTIVE: To quantify the impact on peak airway pressure of pressure
      controlled and volume-controlled ventilation during Laryngeal Mask Airway (LMA)
      use. DESIGN: Prospective, crossover clinical study. SETTING: University
      affiliated hospital. PATIENTS: 32 ASA physical status I and II patients
      undergoing general anesthesia with the LMA. INTERVENTIONS: Patients were
      ventilated for three minutes both with pressure-controlled and volume-controlled
      ventilation, provided that tidal volume (V(T) ) and inspiratory time (It) were
      constant. MEASUREMENTS AND MAIN RESULTS: The monitored parameters were
      electrocardiography, arterial blood pressure, pulse oximetry, capnography,
      neuromuscular transmission, airway pressure and flow, and concentration of
      ventilated vapors and gases. The actually delivered V(T) was similar with both
      types of ventilation (volume-controlled = 0.67 +/- 0.13 lt, pressure-controlled =
      0.67 +/- 0.14 lt; p = 0.688). Peak airway pressure was lower during pressure
      controlled ventilation (14.6 +/- 3.5 cmH(2)O) than during volume-controlled
      ventilation (16 +/- 4 cmH(2)O) (p < 0.001). Furthermore, we noted that the higher
      the airway pressure with volume-controlled ventilation, the greater was the
      reduction in airway pressure during pressure-controlled ventilation. CONCLUSIONS:
      Pressure-controlled rather than volume-controlled ventilation can improve the
      effectiveness of mechanical ventilation in patients with high airway pressure.

PMID- 11578889
TI  - Absorption of lidocaine during aspiration anesthesia of the airway.
AB  - STUDY OBJECTIVE: To determine the optimal solution to use when anesthetizing the
      airway by aspiration of lidocaine. DESIGN: Randomized, double-blind clinical
      study. SETTING: University hospital. PATIENTS: 96 adult ASA physical status 1,II,
      and III patients, scheduled for diagnostic flexible bronchoscopy. INTERVENTIONS:
      Patients were randomized to receive one of 5 solutions of lidocaine: Group A (n =
      16): 1% lidocaine, 0.2 mL. kg(-1); Group B (n = 16): 1.5% 0.2 mL. kg(-1); Group C
      (n = 32): 2% 0.2 mL. kg(-1); Group D (n = 16): 1% 0.3 mL. kg(-1), and Group E (n
      = 16): 2% 0.3 mL. kg(-1). Fiberoptic bronchoscopy was performed after the airway
      was anesthetized with this aspiration technique, using the assigned lidocaine
      solution. The scope was manipulated in the trachea to test for anesthesia.
      MEASUREMENTS AND MAIN RESULTS: Successful airway anesthesia was determined by
      tolerance to bronchoscopy without sustained coughing, and also by the number of
      lidocaine supplements, if any, that were given via the bronchoscope. Arterial
      plasma concentrations of lidocaine were measured in 33 patients from Groups C, D,
      and E. All solutions provided equally effective anesthesia of the airway. All
      patients tolerated endoscopy through the vocal cords, and 94 patients required no
      supplementary anesthesia, or only one dose of lidocaine, during bronchoscopy to
      the carina. The highest peak plasma concentrations of lidocaine were 5.02 and
      6.28 microg. mL. No patient had signs of toxicity. CONCLUSIONS: This technique
      produced anesthesia of the airway to the carina, safely, suitable for awake
      intubation, in 94 of 95 patients. The use of 1% lidocaine, 0.2 to 0.3 mL. kg(-1),
      so that the volume is 10 to 20 mL, is recommended.

PMID- 11578890
TI  - Suppression of cough during emergence from general anesthesia: laryngotracheal
      lidocaine through a modified endotracheal tube.
AB  - STUDY OBJECTIVE: To ascertain if coughing during emergence from general
      anesthesia can be suppressed with a modified endotracheal tube. DESIGN:
      Randomized, double-blind, controlled study. SETTING: Operating rooms at a
      university hospital. PATIENTS: 46 adult ASA physical status I, II, and III
      patients requiring elective surgery. INTERVENTIONS: Patients underwent general
      anesthesia with the laryngotracheal instillation of topical anesthesia (LITA)
      endotracheal tube (ETT). Thirty minutes before anticipated extubation, one
      investigator administered, via the LITA tube injection port onto the
      laryngotracheal mucosa, one of the following according to randomized
      preselection: 2 mg/kg with 4% lidocaine (Group I; n = 15); 4 mL with saline
      (Group 2;n = 16); and nothing (Control; n = 15). At the completion of surgery,
      with the patient adequately anesthetized, the oropharynx was gently suctioned,
      and the isoflurane was then turned off. When the isoflurane end-tidal
      concentration was < or =0.2%, the neuromuscular block was reversed and the
      inspiratory oxygen concentration was increased to 100% while awaiting the return
      of spontaneous ventilation. MEASUREMENTS: An observer who was blinded to the
      study drug regimens judged the presence or absence of cough upon emergence, over
      a 1-minute period. The observer noted the responses to the following verbal
      commands, in this order: 1) "open your eyes", 2) "grip my hand", and 3) "lift
      your head". Coughing was defined as any evidence of irritation from having a tube
      in the trachea. Blood samples for plasma lidocaine levels were taken at the time
      of extubation from patients who received lidocaine (Group 1). MAIN RESULTS:
      Seventy-five percent of patients were found to have complete cough suppression
      upon emergence, while Group 2 (saline) had 14% and Group 3 (the control) only had
      13% suppression. CONCLUSIONS: The technique of laryngotracheal topical lidocaine
      administered by the LITA tube can, in most cases, provide a smooth emergence from
      general anesthesia without coughing.

PMID- 11578891
TI  - Preliminary evaluation of epidural morphine for treatment of heroin withdrawal.
AB  - OBJECTIVE: To evaluate the efficacy of epidural morphine in treating heroin
      withdrawal in patients who failed to detoxify by the other methods. DESIGN:
      Prospective study. SETTING: Department of Psychiatry of a general hospital.
      PATIENTS: 8 ASA physical status I patients, aged 26 to 42 years, not having
      concurrent diseases requiring medication, and who had previously failed other
      methods of detoxification. INTERVENTIONS: Epidural catheters were inserted at the
      L(3)-L(4) interspace. Bolus injections of morphine sulfate, 3.0 mg in normal
      saline, were administered epidurally at 24-hour intervals. Treatment continued
      for 10 to 12 days. MEASUREMENTS: Withdrawal symptoms, such as mydriasis,
      insomnia, rhinorrhea, arthralgia, muscular pain, tooth pain, vomiting, diarrhea,
      dysphoria, and drug craving were monitored. MAIN RESULTS: Withdrawal symptoms
      ceased within 10 days. Withdrawal symptoms were diminished or entirely abolished
      by the treatment, and no patient requested to drop out of the program.
      Discontinuation of the epidural injections did not cause relapse of withdrawal.
      All patients reported that withdrawal with epidural morphine was considerably
      easier compared to other methods that they had previously experienced.
      CONCLUSIONS: A preliminary evaluation of epidural morphine in addicts that failed
      previous detoxifications showed high effectiveness of this method in reducing
      withdrawal symptoms.

PMID- 11578892
TI  - Wrist actigraphy in anesthesia.
AB  - STUDY OBJECTIVES: To examine the use of wrist actigraphy during and following
      anesthesia or monitored sedation and its ability to objectively assess sleep
      related events. DESIGN: Uncontrolled study. SETTING: 1100-bed tertiary care
      municipal, university-affiliated medical center. PATIENTS AND INTERVENTIONS: 18
      patients who underwent minor to medium lower-body surgical procedures with spinal
      or epidural anesthesia with sedation by propofol, midazolam, or isoflurane-based
      general anesthesia. MEASUREMENTS AND MAIN RESULTS: Wrist actigraphy was measured
      and evaluated. The actigraphic recordings accurately indicated the presence and
      time of occurrence of all relevant perioperative events including those related
      to anesthesia. Actigraphic data were more precise than equivalent attending
      anesthesiologist's subjective observations. The anesthesiologist detected changes
      in the patient's activity with a delay of minutes after they had been picked up
      by the actigraph. The integrated areas of recorded phases of midazolam-induced
      sedation and the occurrence and reversal of paradoxical reactions were distinctly
      discernible as such, unlike the less specifically defined description of the
      anesthesiologist. CONCLUSIONS: Real time actigraphic monitoring can provide clear
      cut and objective indications of changes in the depth of anesthesia or sedation
      and its associated events during surgery and recovery.

PMID- 11578893
TI  - Air-oxygen mixtures in circle systems.
AB  - STUDY OBJECTIVE: To determine the effect of different air-O(2) mixtures and fresh
      gas flows (FGF) on the relationship between the delivered (F(Del)O(2)) and
      inspired O(2) fraction (FIO(2)) in a circle system. STUDY DESIGN: Randomized
      clinical study. SETTING: Large teaching hospital. PATIENTS: 160 ASA physical
      status I, II, and III patients undergoing a variety of cardiovascular procedures
      with general endotracheal anesthesia. INTERVENTIONS: 160 patients were randomly
      assigned to one of 20 groups (n = 8 each), depending on the combination of total
      FGF (0.5, 1, 2, 4, or 8 L/min) and air-O(2) mixture used (ratios of 4/1, 3/2,
      2/3, or 1/4), corresponding to a F(Del)O(2) of 0.37, 0.53, 0.68, and 0.84. For
      each combination of FGF and air-O(2) mixture, FIO(2) after equilibration was
      compared with F(Del)O(2). MEASUREMENTS AND MAIN RESULTS: With any air-O(2)
      mixture with a FGF < or = 2 L/min, FIO(2) became lower than F(Del)O(2). Because
      FIO(2) decreased below 0.25 after 13 and 26 minutes in the first two patients of
      the 4/1 0.5 L/min air-O(2) group, this study limb was terminated. CONCLUSIONS:
      When using air-O(2) mixtures in a circle system, FIO(2) becomes lower than the
      F(Del)O(2) with FGF < or = 2 L/min. The relative proportion of O(2) in the FGF
      has to be increased accordingly.

PMID- 11578894
TI  - Structured preoperative patient education for patient-controlled analgesia.
AB  - STUDY OBJECTIVE: To investigate the effectiveness of a structured preoperative
      education program in patients receiving patient-controlled analgesia (PCA).
      DESIGN: Randomized controlled trial. SETTING: University-affiliated hospital.
      PATIENTS: 60 ASA physical status I and II women undergoing major gynecologic
      surgery. INTERVENTIONS: Patients were randomly allocated to receive either
      standard information given during routine preanesthetic assessment (n = 30) or
      additional structured preoperative education on the use of PCA (n = 30).
      MEASUREMENTS: All patients received standard anesthesia and PCA was provided for
      postoperative analgesia. Patients were reviewed bid by an independent team of
      pain specialists and nurses. Patient satisfaction, severity of postoperative
      pain, nausea, dizziness, and morphine consumption were measured at discharge from
      recovery room, 24, and 48 hours after operation. Recovery characteristics of
      patients were also measured. MAIN RESULTS: Pain scores and morphine consumption
      decreased over time (p < 0.01), but there was no significant difference between
      groups. The overall analgesic efficacy, side effects, and recovery times was not
      affected by the education program. Patient satisfaction in the education group
      was better than control during early recovery (p= 0.03), but there was no
      additional benefit in the remaining postoperative period. CONCLUSIONS: Structured
      preoperative PCA education did not affect patient outcome. The early improvement
      in patient satisfaction was minimized by continued education and pain team
      supervision during the rest of the postoperative period.

PMID- 11578895
TI  - The role of species-dependent metabolism in the regional brain retention of 18F
      labeled muscarinic acetylcholine receptor ligands.
AB  - We have developed PET radioligands for the muscarinic acetylcholine receptor
      designed to be sensitive to endogenous acetylcholine changes. These radioligands
      were based on the piperidyl and pyrrolidyl benzilate scaffold and include (R)-N
      (2-[18F]fluoroethyl)-3-piperidyl benzilate (1b), (R)-N-(2-[18F]fluoroethyl)-3
      pyrrolidyl benzilate (2b), and N-(2-[18F]fluoroethyl)-4-piperidyl benzilate (3b).
      In the mouse, intravenous injection of 2b produced a heterogeneous receptor
      mediated regional retention of radioactivity, whereas in the rat a homogeneous
      brain distribution was observed. Analyses of blood and brain extracts showed a
      radiolabeled metabolite for 2b which was formed to a much greater extent in mice
      than rats. This metabolite may have a higher receptor binding affinity than
      authentic 2b, and thus be responsible for the apparent receptor-mediated binding
      in the mouse brain. Our findings emphasize the importance of metabolite analysis
      in multiple species when developing novel radiopharmaceuticals for in vivo use.

PMID- 11578896
TI  - Effect of molecular charges on renal uptake of 111In-DTPA-conjugated peptides.
AB  - The effect of molecular charges on renal accumulation of 111In-DTPA-labeled low
      molecular weight (LMW) peptides was investigated using 111In-DTPA-octreotide
      derivatives as models to design radiolabeled peptides that are taken up less by
      renal cells. The N-terminal D-phenylalanine (Phe) of 111In-DTPA-D-Phe(1)
      octreotide was replaced with L-aspartic acid (Asp), L-lysine (Lys), L-methionine
      (Met) or L-Phe. Cellulose acetate electrophoresis indicated that both 111In-DTPA
      L-Phe(1)-octreotide and 111In-DTPA-L-Met(1)-octreotide showed similar net
      charges, whereas 111In-DTPA-L-alphaLys(1)-octreotide and 111In-DTPA-L-Asp(1)
      octreotide had more positive and negative charges, respectively, at pH values
      similar to those in blood and glomerular filtrate. When injected into mice,
      significant differences were observed in the renal radioactivity levels. 111In
      DTPA-L-alphaLys(1)-octreotide showed the highest radioactivity levels from 10 min
      to 6 h postinjection, whereas the lowest radioactivity levels were observed with
      111In-DTPA-L-Asp(1)-octreotide at all the postinjection intervals. These findings
      indicated that the replacement of only one amino acid in 111In-DTPA-D-Phe(1)
      octreotide significantly altered net molecular charges of the resulting peptides
      and that the net charges of the 111In-DTPA-octreotide derivatives significantly
      affected their renal uptake. Thus, an increase of negative charges in peptide
      molecules may constitute a strategy for designing 111In-DTPA-conjugated LMW
      peptides with low renal radioactivity levels.

PMID- 11578897
TI  - Positively charged templates for labeling internalizing antibodies: comparison of
      N-succinimidyl 5-iodo-3-pyridinecarboxylate and the D-amino acid peptide KRYRR.
AB  - Receptor-mediated internalization of monoclonal antibodies (mAbs), such as those
      specific for the epidermal growth factor receptor variant III (EGFRvIII), can
      lead to rapid loss of radioactivity from the target cell. In the current study,
      the anti-EGFRvIII mAb L8A4 was radioiodinated using two methods -N-succinimidyl 5
      iodo-3-pyridinecarboxylate (SIPC) and via a D-amino acid peptide LysArgTyrArgArg
      (D-KRYRR). Paired-label internalization assays performed on EGFRvIII-expressing
      U87DeltaEGFR cells in vitro demonstrated that labeling L8A4 using D-KRYRR
      resulted in significantly higher retention of radioiodine in the intracellular
      compartment. In athymic mice with D256 human glioma xenografts, tumor uptake was
      similar for both labeling methods through 24 hr. However, an up to fourfold
      higher tumor retention was observed for mAb labeled with the D-amino acid peptide
      at later time points. Radiation absorbed dose calculations based on these
      biodistribution data indicated that L8A4 labeled using D-KRYRR exhibited better
      tumor-to-normal-organ radiation dose ratios, suggesting that this labeling method
      may be of particular value for labeling internalizing mAbs.

PMID- 11578898
TI  - Species differences in [11C]clorgyline binding in brain.
AB  - [11C]Clorgyline selectively binds to MAO A in the human brain. This contrasts
      with a recent report that [11C]clorgyline (in contrast to other labeled MAO A
      inhibitors) is not retained in the rhesus monkey brain [4]. To explore this
      difference, we compared [11C]clorgyline in the baboon brain before and after
      clorgyline pretreatment and we also synthesized deuterium substituted
      [11C]clorgyline (and its nor-precursor) for comparison. [11C]Clorgyline was not
      retained in the baboon brain nor was it influenced by clorgyline pretreatment or
      by deuterium substitution, contrasting to results in humans. This suggests a
      species difference in the susceptibility of MAO A to inhibition by clorgyline and
      represents an unusual example of where the behavior of a radiotracer in the
      baboon brain does not predict its behavior in the human brain.

PMID- 11578899
TI  - [11C]Raclopride binding was reduced in vivo by sigma(1) receptor ligand SA4503 in
      the mouse brain, while [11C]SA4503 binding was not by raclopride.
AB  - [11C]Raclopride is widely used as a representative dopamine D(2)-like receptor
      ligand in positron emission tomography (PET) studies, and [11C]1-(3,4
      dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride ([11C]SA4503) is
      a recently developed selective ligand for mapping sigma(1) receptors in the
      brain. The striatal uptake of [11C]raclopride in mice was reduced by co-injection
      of an excess amount of SA4503, in spite of the fact that raclopride had no effect
      on the brain uptake of [11C]SA4503 as shown in a previous study. The blocking
      effect of SA4503 on the striatal uptake of [11C]raclopride was dose-dependent,
      but disappeared by 1 h or 6 h after intraperitoneal injection of SA4503. The
      brain uptake of [11C]SA4503 was not affected by a dopamine transporter inhibitor
      GBR 12909, nor was [11C]beta-CIT-FP inhibited by SA4503. The IC(50) values of
      raclopride for sigma(1) and sigma(2) receptor subtypes measured in vitro were
      11800 nM and 4950 nM, respectively, suggesting that the affinity was too low for
      [11C]raclopride to bind in vivo to sigma receptors. On the other hand, the IC(50)
      value of SA4503 for dopamine D(2) receptors was 470 nM, that is approximate 1/25
      of the affinity of raclopride for the dopamine D(2) receptors. Therefore,
      possible explanations for the partial blocking effects of SA4503 on the striatal
      uptake of [11C]raclopride are: (1) an excess amount of SA4503 may reduce the
      [11C]raclopride uptake due to its low affinity for dopamine D(2) receptors, or
      (2) SA4503 may enhance endogenous dopamine release, which results in the
      competitive inhibition of the [11C]raclopride uptake. These findings support that
      both [11C]raclopride and [11C]SA4503 are selective in vivo ligands for dopamine
      D(2)-like receptors and sigma(1) receptors, respectively, in spite of the partial
      blocking effect of SA4503 on the striatal uptake of [11C]raclopride.

PMID- 11578900
TI  - Investigation of a potential scintigraphic marker of apoptosis: radioiodinated Z
      Val-Ala-DL-Asp(O-methyl)-fluoromethyl ketone.
AB  - The imaging of apoptosis represents an attractive diagnostic goal in the area of
      tumor therapy, degenerative diseases and organ transplantation. Since caspases
      play a key role during the early period of the intracellular signal cascade of
      cells undergoing apoptosis we considered benzyloxycarbonyl-Val-Ala-DL-Asp(O
      methyl)-fluoromethyl ketone [Z-VAD-fmk], a pan-caspase inhibitor, as a potential
      apoptosis imaging agent. Applying the Tl(TFA)(3)/[131I]iodide method Z-VAD-fmk
      was successfully labeled at the benzyloxycarbonyl protecting group. The success
      of radioiodination, however, depended on the presence of carrier iodide resulting
      in specific radioactivities of 2.6 GBq/micromol and the formation of a mixture of
      the 2- and 4-iodophenyl derivative (61%) which could not be separated by HPLC.
      Uptake measurements were performed with Morris hepatoma cells (MH3924Atk8) which
      showed expression of the Herpes Simplex Virus thymidine kinase (HSVtk) gene.
      Apoptosis was induced by treatment of the cells with 25 microM ganciclovir. The
      TUNEL assay revealed 1.3 +/-0.3 and 23 +/-1.1% apoptotic cells immediately and 24
      h after therapy, respectively. A two-fold increase of [131I]IZ-VAD-fmk uptake was
      found at the end of treatment with the HSVtk/suicide system which constantly
      remained elevated for the following 4 hours. The slow cellular influx and lack of
      uptake saturation of [131I]IZ-VAD-fmk are evidence for simple diffusion as
      transport mechanism. In addition, the absolute cellular uptake of [131I]IZ-VAD
      fmk was found to be low. This quality was related to the rather high
      lipophilicity of [131I]IZ-VAD-fmk causing unspecific binding to macromolecules in
      the medium. Instead of using an inhibitor, synthetic caspase substrates are
      currently investigated which may accumulate in the apoptotic cell by metabolic
      trapping thereby enhancing the imaging signal.

PMID- 11578902
TI  - Biodistribution, binding specificity and metabolism of [18F]fluoroethylflumazenil
      in rodents.
AB  - Pre-clinical studies were carried out in order to characterize in rodents the
      biodistribution, the binding specificity and the metabolism of
      [18F]Fluoroethylflumazenil ([18F]FEF), a potential candidate for in vivo imaging
      of the benzodiazepine receptors. In vivo competition with flumazenil indicates
      that [18F]FEF binds specifically to the benzodiazepine receptor in the brain. The
      accumulation of [18F]FEF was significantly lower than using [3H]Flumazenil. The
      rather low accumulation in the brain is due to a rapid metabolism of [18F]FEF in
      hydrophylic metabolites which cannot cross the blood brain barrier, and are
      rapidly eliminated in the urine. Inhibition of the metabolism by acetaminophen
      (chemically induced hepatitis) led to a significant increase of the radioactivity
      found in the circulating blood and in the brain, while these results were not
      observed using classical inhibitors of the cytochrome CYP450, cimetidine and
      ketoconazole.

PMID- 11578901
TI  - Synthesis, characterization and comparative biodistribution study of a new series
      of p-iodine-125 benzamides as potential melanoma imaging agents.
AB  - Iodobenzamides are reported to possess some affinity for melanoma. In order to
      identify the compound having the most appropriate pharmacokinetic properties as a
      potential melanoma imaging agent, thirteen new [125I]radioiodobenzamides with a
      butylene amide-amine spacer and various substituents on the terminal amino group
      were investigated. Their synthesis, radioiodination and biodistribution in B16
      melanoma bearing C57BL6 mice are described and compared to [125I] labeled N-(2
      diethylaminoethyl)-4-iodobenzamide ([125I]BZA), our reference compound. Changes
      in the terminal amino constituents induced modifications of lipophilicity, tumor
      uptake and organ distribution. The dimethylaminobutyl iodobenzamide appeared to
      be the most promising radiopharmaceutical imaging agent for the detection of
      melanoma and its metastases.

PMID- 11578903
TI  - [18F] labeled diacylglycerol analogue as a potential agent to trace myocardial
      phosphoinositide metabolism.
AB  - Phosphoinositide metabolism plays an important role in cardiac pathophysiology.
      To investigate whether [18F]diacylglycerol could be used to trace myocardial
      phosphoinositide metabolism, lipids were extracted from rat myocardium after the
      injection. 1-[8-[18F]fluorooctanoyl]-2-palmitoylglycerol and 1-[8
      [18F]fluoropalmitoyl]-2-palmitoylglycerol were predominantly metabolized to
      phosphatidylethanolamine and triacylglycerol, respectively. The radioactivity
      incorporated into phosphoinositide metabolism was 51, 44, 32, and 30% 3, 5, 10,
      and 30 minutes after the injection of 1-[4-[18F]fluorobutyryl]-2
      palmitoylglycerol, respectively. 1-[4-[18F]fluorobutyryl]-2-palmitoylglycerol
      might be a potential tracer to evaluate myocardial phosphoinositide metabolism
      early after the injection.

PMID- 11578904
TI  - Pretargeting of human mammary carcinoma xenografts with bispecific anti-MUC1/anti
      Ga chelate antibodies and immunoscintigraphy with PET.
AB  - We recently demonstrated the feasibility of combining enhanced tumor-to-tissue
      contrast and PET imaging for immunoscintigraphic tumor localization in pancreas
      and colon carcinoma bearing nude mice. Contrast enhancement was obtained with a
      multistep targeting technique that consists of the sequential administration of
      an antitumor/antihapten bispecific antibody (BS-MAb), a blocker to saturate the
      antihapten binding sites of the BS-MAb that remains in circulation, and a low
      molecular weight Ga chelate, labeled with the positron emitter 68Ga, which serves
      as the hapten. To evaluate the efficacy of this pretargeting technique for breast
      cancer localization, we synthesized a BS-MAb from the F(ab')(2) fragments of the
      anti-MUC1 MAb 12H12 which reacts with the vast majority of human breast
      carcinomas, and the F(ab') fragment of an anti-Ga chelate MAb using a
      bifunctional chemical linker. The BS-MAb was tested for its affinity and its
      biokinetics in nude mice bearing a human mammary carcinoma. Equilibrium binding
      of the BS-MAb for mammary carcinoma cells was low (1.2 x 10(7) M(-1)) while the
      binding capacity of cells was high (8.4 x 10(6) BS-MAbs per cell). Tumor uptake
      of the 67Ga labeled chelate in pretargeted animals was to 5.8 +/- 0.8% iD/g
      resulting in a tumor-to-blood ratio of 2.6 at 1h postinjection. This compares
      with a ratio of 0.65 and 0.85 obtained with 125I-labeled native 12H12 at 24h and
      48h postinjection. No difference in the tumor uptake of both the 68Ga and 67Ga
      labeled chelate was observed. PET imaging of mice, started 1h postinjection of
      the 68Ga chelate, clearly visualized all tumors.

PMID- 11578905
TI  - Correlation between 99mTc-pertechnetate uptakes and expressions of human sodium
      iodide symporter gene in breast tumor tissues.
AB  - We investigated a correlation between the expression of human sodium iodide
      symporter (hNIS) mRNA and the uptake of 99mTc-pertechnetate in 25 breast tumors.
      99mTc-pertechnetate scintigraphy revealed positive uptake in 4 patients. The
      normalized mRNA expression of hNIS was higher in tumors with positive uptake on
      the scintigraphy (n=4, median 0.97, range 0.78-1.27) than that in negative uptake
      tumors (n=21, median 0.46, range 0.10-1.03, p < 0.005). 99mTc-pertechnetate
      uptake is correlated with the hNIS expression in the breast tumor.

PMID- 11578906
TI  - Efficacy of Re-188-labelled sulphur colloid on prolongation of survival time in
      melanoma-bearing animals.
AB  - In this study, the effectiveness of a 188Re labeled sulfur colloid with two
      particle size ranges was used to evaluate the effectiveness of this agent on
      melanoma tumors in mice in terms of animal lifespan. METHODS: Two separate group
      of animals were used for investigating biodistribution and survival time. A total
      of 188 B16F10-melanoma-bearing BDF(1) mice were injected intraperitoneally with
      3.7 MBq (0.1mCi)/2mL of radiolabeled sulfur colloid ten days after
      intraperitoneal inoculation of 5x10(5) B16F10 melanoma cells/2ml. For group 1, 30
      mice were sacrificed at 1, 4, 24, 48 and 72 hours for biodistribution studies. In
      group 2, 158 mice were divided into 9 groups (n=16 approximately 18/groups)each
      receiving respectively tumor alone, tumor with normal saline, cold colloid or hot
      colloid with 16, 23, 31, 46, 62, or 124 MBq activity. Each of these colloid
      groups was further divided into two groups, one receiving smaller particle sizes
      (<3 microm:80.4 +/-7.2%, colloid 1) and the other receiving larger particle sizes
      (<3 microm:12.3+/-1.0%, colloid 2). The animals were checked daily until death
      and their survival recorded. RESULTS: Colloid 2 showed higher accumulation in
      almost all tissues, the highest accumulation organ was tumor ( approximately
      40%), then spleen ( approximately 20%), stomach ( approximately 15%), diaphragm (
      approximately 3%), and liver ( approximately 2%). There was a significant
      increase in survival time with increasing amount of the larger-particle-size
      colloid. Administered levels of 16-31 MBq/mouse were most efficacious and with
      higher amounts the survival times decreased significantly below that of the
      controls. There was a significant difference in the dose-response curves for the
      two preparations. Protection factors (1/Relative-risk) of nearly 5 were achieved
      using the larger colloid size, and nearly 30 using the smaller colloid size. An
      amount of 16-31 MBq of the colloid 2 was the optimal activity in these studies.
      On the one hand, the survival data agreed well with the biodistribution data,
      where higher accumulation was found in tumor with colloid 2. CONCLUSION: Rhenium
      188 offers on-site availability, medium half-life, higher beta-particle energy of
      2.12 MeV for therapy and emission of 155keV gamma photon suitable for imaging.
      The present study demonstrated that 188Re-sulfur colloid is an effective agent in
      controlling tumor cells in the abdominal cavity in animals.

PMID- 11578907
TI  - Preparation and in vivo evaluation of linkers for 211At labeling of humanized
      anti-Tac.
AB  - The syntheses, radiolabeling, antibody conjugation, and in vivo evaluation of new
      linkers for 211At labeling of humanized anti-Tac (Hu-anti-Tac), an antibody to
      the alpha-chain of the IL-2 receptor (IL-2Ralpha) shown to be a useful target for
      radioimmunotherapy are described. Synthesis of the organometallic linker
      precursors is accomplished by reaction of the corresponding bromo- or iodoaryl
      esters with bis(tributyltin) in the presence of a palladium catalyst. Subsequent
      conversion to the corresponding N-succinimidyl ester and labeling with 211At of
      two new linkers, N-succinimidyl 4-[211At]astato-3-methylbenzoate and N
      succinimidyl N-(4-[211At]astatophenethyl)succinamate (SAPS), together with the
      previously reported N-succinimidyl 4-[211At]astatobenzoate and N-succinimidyl 3
      [211At]astato-4-methylbenzoate, are each conjugated to Hu-anti-Tac. The plasma
      survival times of these conjugates are compared to those of directly iodinated
      (125I) Hu-anti-Tac. The N-succinimidyl N-(4-[211At]astatophenethyl)succinamate
      compound (SAPS) emerged from this assay as the most viable candidate for 211At
      labeling of Hu-anti-Tac. SAPS, along with the directly analogous radio-iodinated
      reagent, N-succinimidyl N-(4-[125I]astatophenethyl)succinamate (SIPS), are
      evaluated in a biodistribution study along with directly iodinated (125I) Hu-anti
      Tac. Blood clearance and biological accretion results indicate that SAPS is a
      viable candidate for further evaluation for radioimmunotherapy of cancer.

PMID- 11578909
TI  - 99mTc-labeling experiments on CCK(4) by a direct method.
AB  - 99mTc-labeling studies have been performed on CCK(4) fragment of cholecystokinin,
      starting from 99mTc-pertechnetate, by using tin(II)pyrophosphate or
      tin(II)gluconate as reducing agents, together with NaBH(4) acting as a
      stabilizing agent of tin(II). Gluconate has been used as exchange ligand in the
      carrier added experiments and in the syntheses of 99Tc-CCK(4) and Re-CCK(4)
      complexes to be able to reproduce at macroscopic level the same chemical
      reactions occurring at non carrier added conditions. 99mTc-labeling yields higher
      than 95% have been achieved depending on Sn(II) concentration, CCK(4)/gluconate
      ratio, reaction time and applied temperature. The species produced with 99mTc,
      99Tc, and cold rhenium nuclides have been compared by means of HPLC measurements,
      which showed similar retention times and thus probably the same species in the
      three situations.

PMID- 11578908
TI  - Synthesis of S-([18F]fluoromethyl)-(+)-McN5652 as a potential PET radioligand for
      the serotonin transporter.
AB  - The present study describes the synthesis of the [18F]fluoromethyl analogue of
      (+)-McN5652 ([18F]FMe-McN) as a new potential tracer for the serotonin
      transporter. In vitro binding studies have shown that FMe-McN displays only
      slightly lower affinity for the serotonin transporter (K(i) = 2.3 +/- 0.1 nM)
      than (+)-McN5652 (K(i) = 0.72 +/- 0.2 nM). The radiofluorinated tracer [18F]FMe
      McN was prepared by reaction of normethyl (+)-McN5652 with the fluoromethylation
      agent [18F]bromofluoromethane in an overall radiochemical yield of 5 +/- 1%
      (decay-corrected, related to [18F]fluoride) and with high specific radioactivity
      (200-2,000 GBq/micromol at the end of synthesis).

PMID- 11578911
TI  - Monoclonal antibodies and cancer.

PMID- 11578910
TI  - A simplified one-pot synthesis of 9-[(3-[18F]fluoro-1-hydroxy-2
      propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]fluoro-3
      hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy.
AB  - 9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG, 2) has been
      synthesized by nucleophilic substitution of N(2)-(p-anisyldiphenylmethyl)-9-[[1
      (p-anisyldiphenylmethoxy)-3-toluenesulfonyloxy-2-propoxy]methyl]guanine (1) with
      potassium [18F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and
      purification with different methods in variable yields. When both the
      nucleophilic substitution and deprotection were carried out at 90 degrees C and
      the product was purified by HPLC (method A), the yield of compound 2 was 5-10%
      and the synthesis time was 90 min from EOB. However, if both the nucleophilic
      substitution and deprotection were carried out at 120 degrees C and the product
      was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2
      was synthesized at 90 degrees C and purified by Silica Sep-Pak (method B), the
      yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly,
      9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG, 4) was synthesized with
      method A and method B in 9% and 10-15% yield, respectively, in a synthesis time
      of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in
      acidic medium at 120 degrees C while compound 4 was stable under the same
      condition. Both compound 2 and compound 4 had low lipid/water partition
      coefficient (0.126 +/- 0.022, n=5 and 0.165 +/- 0.023, n=5, respectively).
      Although it contains non-radioactive ganciclovir ( approximately 5-30 microg) as
      a chemical by-product, compound 2 synthesized by method B has a similar uptake in
      9L glioma cells as that synthesized by method A, and is a potential tracer for
      imaging herpes simplex virus thymidine kinase gene expression in tumors using
      PET. Similarly, compound 4 synthesized by method B contains approximately 10-25
      microg of penciclovir as a chemical by-product. Thus, the simplified one pot
      synthesis (method B) is a useful method for synthesizing both compound 2 and
      compound 4 in good yield for routine clinical use, and the method is readily
      amenable for automation.

PMID- 11578912
TI  - Rituximab: perspective on single agent experience, and future directions in
      combination trials.
AB  - The chimeric anti-CD20 antibody rituximab is the first monoclonal antibody to
      gain regulatory approval for the treatment of any malignancy. As such, its
      development represents a major milestone in cancer therapy. It is an effective
      single agent for patients with CD20-positive B-cell malignancies, using a well
      tolerated and brief (weekly x 4) schedule that has become the accepted standard.
      Since this weekly x 4 schedule is not a maximum tolerated dose, additional
      research is being done on different doses and schedules of rituximab. Researchers
      are also exploring the use of rituximab in conjunction with cytokines or
      chemotherapy. Further developments in the use of rituximab and other targeted
      therapy approaches can be expected as we learn more about the mechanisms of
      action of, and resistance to, rituximab.

PMID- 11578913
TI  - Clinical experience with edrecolomab: a monoclonal antibody therapy for
      colorectal carcinoma.
AB  - Edrecolomab (monoclonal antibody 17-1A) is a murine monoclonal antibody that
      recognizes the human tumor-associated antigen Ep-CAM (otherwise known as 17-1A).
      It is being developed for the adjuvant treatment of colorectal cancer. In a study
      of 189 patients with resected stage III colorectal cancer, treatment with
      edrecolomab resulted in a 32% increase in overall survival compared with no
      treatment (P<0.01) and decreased the tumor recurrence rate by 23% (P<0.04). In
      terms of safety, edrecolomab was well tolerated. Based on these study results,
      edrecolomab is currently under investigation in large multicenter phase III
      studies both as monotherapy and in combination with 5-fluorouracil-based
      chemotherapy versus chemotherapy alone for the treatment of stage III colon
      cancer. Although these studies are still ongoing, an interim analysis of safety
      data indicated that the combination of edrecolomab with chemotherapy is well
      tolerated. In addition, edrecolomab monotherapy demonstrated a favorable safety
      profile compared with chemotherapy. Edrecolomab is also currently being tested in
      large multicenter adjuvant phase III studies in stage II/III rectal cancer and
      stage II colon cancer. Edrecolomab represents a novel therapeutic approach and
      has the potential to become a treatment of choice as monotherapy in stage II
      colon cancer and in combination with chemotherapy in stage II/III rectal and
      stage III colon cancer.

PMID- 11578914
TI  - A review of modifications to recombinant antibodies: attempt to increase efficacy
      in oncology applications.
AB  - Although monoclonal antibodies have high specificity, their usefulness in the
      clinic, especially against solid tumors, has been limited. This arises in part
      from the inability of antibody molecules to penetrate into the tumor and kill the
      tumor cells. In addition, natural cytotoxic effects of antibodies, mediated
      through complement or Fc receptors, may not be sufficient to kill malignant
      cells. This review will present some of the antibody modifications used to
      increase efficacy. Modified recombinant antibodies have been designed to be more
      cytotoxic (immunotoxins), to increase natural effector functions (bivalent
      antibodies, antibody-fusion molecules, multimeric antibodies, directed mutations
      in Fc region), or to pretarget cells for concentration of cytotoxic drugs. This
      review will also focus on engineering of smaller versions of antibodies that
      retain specificity (single chain Fvs, Fabs, Fab(2)s, minibodies, domain deleted
      antibodies) and have increased penetrability of solid tumors. Many of these
      antibody modifications may result in antigenic compounds which can limit repeat
      administration. Clinical experiences will be highlighted if information is
      available.

PMID- 11578915
TI  - Pretargeted radioimmunotherapy (PRIT) for treatment of non-Hodgkin's lymphoma
      (NHL).
AB  - Pretargeted radioimmunotherapy (PRIT) was first investigated in a series of phase
      I and phase II studies in patients with adenocarcinoma using a pancarcinoma
      antibody, NR-LU-10. The principles and schema developed were then applied to an
      initial study in patients with non-Hodgkin's lymphoma (NHL). The PRIT approach
      used is a multi-step delivery system in which an antibody is used to target
      streptavidin to a tumor-associated antigen receptor, and subsequently, biotin is
      used to target the 90Y radioisotope to the tumor localized streptavidin. In the
      NHL study, a chimeric, IgG1, anti-CD20 antibody (Rituximab) was conjugated to
      streptavidin (SA) and administered to patients. Thirty-four hours later, a
      clearing agent, synthetic biotin-N-acetyl-galactosamine, was administered to
      remove non-localized conjugate from the circulation. Finally, a DOTA-biotin
      ligand, labeled with 111In for imaging and/or 90Y for therapy was administered.
      Ten patients with relapsed or refractory NHL were studied, and seven received 30
      or 50 mCi/m(2) 90Y DOTA-biotin. Preliminary studies using 186Re labeled conjugate
      confirmed that it localized to tumor and that the clearing agent removed >95% of
      the conjugate from the circulation. Radiolabeled biotin localized well to tumor.
      Unbound radiobiotin was rapidly excreted from the whole body and normal organs.
      The mean tumor dose calculated was 29+/-23 cGy/mCi 90Y, and the mean tumor to
      whole body dose ratio was 38:1. Only grade I/II non-hematologic toxicity was
      observed. Hematologic toxicity was also not severe; i.e. five of the seven
      patients who received 30 or 50 mCi/m(2) of 90Y-DOTA-biotin experienced only
      transient grade III (but no grade IV) hematologic toxicity. Although six of 10
      patients developed humoral immune responses to the streptavidin, these were
      delayed and transient and hence may not preclude retreatment. Six of seven
      patients who received 30 or 50mCi/m(2) 90Y achieved objective tumor regression,
      including three complete and one partial response. The estimate of tumor to whole
      body dose ratio (38:1) achieved with PRIT in these NHL patients is higher than
      that achieved in other studies using conventional RIT. Toxicity was mild and
      tumor response encouraging. PRIT clearly deserves additional study in patients
      with NHL.

PMID- 11578916
TI  - Cancer immunotherapy: insights from transgenic animal models.
AB  - A wide range of strategies in cancer immunotherapy has been developed in the last
      decade, some of which are currently being used in clinical settings. The
      development of these immunotherapeutical strategies has been facilitated by the
      generation of relevant transgenic animal models. Since the different strategies
      in experimental immunotherapy of cancer each aim to activate different immune
      system components, a variety of transgenic animals have been generated either
      expressing tumor associated, HLA, oncogenic or immune effector cell molecule
      proteins. This review aims to discuss the existing transgenic mouse models
      generated to study and develop cancer immunotherapy strategies and the variable
      results obtained. The potential of the various transgenic animal models regarding
      the development of anti-cancer immunotherapeutical strategies is evaluated.

PMID- 11578917
TI  - The difference in gastric cancer between Japan, USA and Europe: what are the
      facts? what are the suggestions?
AB  - In Japan the survival rate for gastric cancer has steadily improved over the last
      30 years whilst that in the West has remained static and inferior. In this review
      three hypotheses are examined to explain the difference. There is little evidence
      to suggest genetic differences, which might result in a less aggressive cancer in
      Japan. Recently there has been a rise in the proportion of cancers of the gastro
      oesophageal junction in the West and this has not been seen in Japan. The
      comparison of survival data from these two regions is problematic with different
      staging systems and a stage migration effect. The established surgical treatment
      of gastric cancer in Japan is radical gastrectomy and regional lymphadenectomy
      and this has been proposed as a superior treatment to the standard gastrectomy
      common in the West. The results for survival benefit however, have not been
      reproduced in randomized clinical trials. The heterogeneity of adjuvant and
      neoadjuvant treatment regimens in Japan and the West has led to difficulties in
      the interpretation of their effects. There is considerable scope for future
      collaboration between clinicians in the West and Japan.

PMID- 11578920
TI  - Activation of dihydrogen without transition metals.
AB  - The metal-free hydrogenase from methanogenic archaea (Hmd) is a unique enzyme: it
      catalyzes the reaction of its substrate, methenyl-tetrahydromethanopterin, with
      molecular hydrogen without the aid of a transition metal. In other words, Hmd is
      currently the only example of a purely organic hydrogenation catalyst. Recent
      results from various fields have shed new light on this enzyme. In biochemistry,
      there is experimental proof that a tightly bound (and metal-free) cofactor
      exists. Ab initio calculations have revealed that the concerted action of the
      Lewis-acidic substrate and a Bronsted-base appears to induce facile heterolysis
      of the hydrogen molecule. In chemical model studies, a transition-metal-free
      hydrogenation of ketones was achieved in the presence of catalytic base. Taken
      together, the experimental results available to date point to an enzymatic
      mechanism in which the hydrogen molecule is heterolyzed by the joint action of
      the Lewis-acidic substrate methenyl-tetrahydromethanopterin and a Bronsted-base
      in the active site (i.e. by bifunctional catalysis).

PMID- 11578921
TI  - The mechanism of action of DNA photolyases.
AB  - Structural analysis, biochemistry and model studies have provided new insights
      into the mechanism of action of photolyases. The light-driven electron and energy
      transfer events that lead to the photolyase-catalyzed repair of lethal, mutagenic
      and carcinogenic UV-light-induced DNA lesions have all been examined in the past
      few years.

PMID- 11578922
TI  - Adenosylcobalamin-dependent isomerases: new insights into structure and
      mechanism.
AB  - Adenosylcobalamin-dependent isomerases catalyze a variety of chemically difficult
      1,2-rearrangements that proceed through a mechanism involving free radical
      intermediates. These radicals are initially generated by homolysis of the cobalt
      carbon bond of the coenzyme. Recently, the crystal structures of several of these
      enzymes have been solved, revealing two modes of coenzyme binding and
      highlighting the role of the protein in controlling the rearrangement of reactive
      substrate radical intermediates. Complementary data from kinetic, spectroscopic
      and theoretical studies have produced insights into the mechanism by which
      substrate radicals are generated at the active site, and the pathways by which
      they rearrange.

PMID- 11578923
TI  - Adenosylmethionine as a source of 5'-deoxyadenosyl radicals.
AB  - The combination of an iron-sulfur cluster and S-adenosylmethionine provides a
      novel mechanism for the initiation of radical catalysis in an unanticipated
      variety of metabolic processes. Molecular details of the cluster-mediated
      reductive cleavage of S-adenosylmethionine to methionine and, presumably, a 5'
      deoxyadenosyl radical are the targets of recent studies.

PMID- 11578924
TI  - Methylidene-imidazolone: a novel electrophile for substrate activation.
AB  - The recent three-dimensional structure of histidine ammonia-lyase revealed that
      the enzyme contains a 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) ring,
      which forms autocatalytically from an Ala-Ser143-Gly triad. This novel prosthetic
      group, which is also present in phenylalanine ammonia-lyase, activates substrates
      by electrophilic interaction. Modern analytical methods, theoretical calculations
      and molecular biology tools have given further insight into the mode of action of
      MIO.

PMID- 11578925
TI  - Tailoring enzymes that modify nonribosomal peptides during and after chain
      elongation on NRPS assembly lines.
AB  - Nonribosomal peptide synthetases are large enzyme complexes that synthesize a
      variety of peptide natural products through a thiotemplated mechanism. Assembly
      of the peptides proceeds through amino acid loading, amide-bond formation and
      chain translocation, and finally thioester lysis to release the product. The
      final products are often heavily modified, however, through methylation,
      epimerization, hydroxylation, heterocyclization, oxidative cross-linking and
      attachment of sugars. These activities are the province of specialized enzymes
      (either embedded in the multidomain nonribosomal peptide synthetase structure or
      standalone).

PMID- 11578926
TI  - The non-mevalonate pathway of isoprenoids: genes, enzymes and intermediates.
AB  - Although the mevalonate pathway had been considered for a long time as the unique
      source of biosynthetic isoprenoids, an alternative pathway has recently been
      discovered. The first intermediate, 1-deoxy-D-xylulose 5-phosphate, is assembled
      by condensation of glyceraldehyde 3-phosphate and pyruvate. A skeletal
      rearrangement coupled with a reduction step affords the branched-chain polyol, 2C
      methyl-D-erythritol 4-phosphate, which is subsequently converted into a cyclic
      2,4-diphosphate by the consecutive action of three enzymes via nucleotide
      diphosphate intermediates. The genes specifying these enzymes have been cloned
      from bacteria, plants and protozoa. Their expression in recombinant bacterial
      hosts has opened the way to the identification of several novel pathway
      intermediates.

PMID- 11578927
TI  - Enzymology of carbon-sulfur bond formation.
AB  - Mobilization of the sulfur of cysteine as persulfide is the first step of sulfur
      transfer into thiamin, molydopterin, 4-thiouridine, biotin and lipoic acid, but
      then the pathways diverge completely. For the first three compounds, one or
      several proteinic persulfides are involved, ending in the nucleophilic attack of
      a sulfur, persulfide, sulfide or thiocarboxylate on a carbonyl equivalent.
      Several proteins have been newly characterized, revealing homologies between the
      three biosynthetic routes and evolutionary relationships. In the case of biotin,
      and very probably of lipoic acid, the sulfur is transferred as sulfide into the
      [Fe-S] center of the enzyme. This [Fe-S] center is the ultimate sulfur donor,
      which quenches a carbon radical on the substrate. This radical is produced by
      homolytic cleavage of a C-H bond by a deoxyadenosyl radical arising from the
      reduction of S-adenosylmethionine.

PMID- 11578928
TI  - Oxygenases: mechanisms and structural motifs for O(2) activation.
AB  - Recent structural and mechanistic analysis of oxygenase enzymes together with the
      study of biomimetic model reactions have provided new insights into the catalytic
      mechanisms of oxygenase-catalysed reactions. High-valent iron-oxo intermediates
      have been implicated in heme- and pterin-dependent mono-oxygenases. Structural
      motifs have been identified for binding of non-heme iron(II) (His,His,Glu) and
      iron(III) (His(2)Tyr(2)) in non-heme-dependent dioxygenases, but additional
      factors influencing the choice of reaction pathway are emerging from model
      studies.

PMID- 11578929
TI  - Transition state variation in enzymatic reactions.
AB  - Experimental analysis of enzymatic transition states by kinetic isotope effect
      methods has established geometric variation in related transition state
      structures. Differences are apparent in development of the reaction coordinate,
      in solvolytic transition states relative to those in enzymatic catalytic sites,
      in the stereochemistry of related substrates at the transition state, and in
      reactions catalyzed by related enzymes.

PMID- 11578931
TI  - Synchrotron radiation circular dichroism spectroscopy of proteins: secondary
      structure, fold recognition and structural genomics.
AB  - Recent developments in instrumentation and bioinformatics show that the technique
      of synchrotron radiation circular dichroism spectroscopy can provide novel
      information on protein secondary structures and folding motifs, and has the
      potential to play an important role in structural genomics studies, both as a
      means of target selection and as a high-throughput, low-sample-requiring
      screening method. This is possible because of the additional information content
      in the low-vacuum ultraviolet wavelength data obtainable with intense synchrotron
      radiation light sources, compared with that present in spectra from conventional
      lab-based circular dichroism instruments.

PMID- 11578932
TI  - Surface plasmon resonance: towards an understanding of the mechanisms of
      biological molecular recognition.
AB  - With the introduction of new instruments and improved sensor chip chemistries,
      surface plasmon resonance (SPR) is finding new applications for molecular
      interaction studies. Easy access to high-quality kinetic and thermodynamic data
      for macromolecular binding events is providing insights into the fundamental
      mechanisms of molecular recognition. Progress is being made to allow larger-scale
      interaction studies. In addition, combining SPR with other analytical methods is
      enabling SPR-based analysis of interaction proteomics.

PMID- 11578933
TI  - Detection of protein-protein interactions in vivo based on protein splicing.
AB  - In mammalian cells, protein-protein interactions constitute essential regulatory
      steps that modulate the activity of signaling pathways. In recent years, several
      approaches towards understanding the interactions have been developed. We
      describe herein a new method for detecting protein-protein interactions in vivo
      based on protein splicing and highlight some potential applications of this
      technique.

PMID- 11578934
TI  - Partial alignment of biomolecules: an aid to NMR characterization.
AB  - Partial alignment of biomolecules in solution has added a new dimension to
      structural investigation by high-resolution NMR methods. Applications to
      proteins, nucleic acids and carbohydrates now abound. Limitations initially
      associated with compatibility of biomolecules with the liquid-crystal media
      commonly used to achieve alignment have begun to disappear. This is, in part, a
      result of the introduction of a wide variety of new media. Future applications to
      biologically important problems such as the structural organization of multi
      domain proteins and multi-protein assemblies look very promising.

PMID- 11578935
TI  - Analysis of phosphorylated proteins and peptides by mass spectrometry.
AB  - Phosphorylation on serine, threonine and tyrosine residues is an extremely
      important modulator of protein function. Therefore, there is a great need for
      methods capable of accurately elucidating sites of phosphorylation. Although full
      characterization of phosphoproteins remains a formidable analytical challenge,
      mass spectrometry has emerged as an increasingly viable tool for this task. This
      review summarizes the methodologies currently available for the analysis of
      phosphoproteins by mass spectrometry, including enrichment of compounds of
      interest using immobilized metal affinity chromatography and chemical tagging
      techniques, detection of phosphopeptides using mass mapping and precursor ion
      scans, localization of phosphorylation sites by peptide sequencing, and
      quantitation of phosphorylation by the introduction of mass tags. Despite the
      variety of powerful analytical methods that are now available, complete
      characterization of the phosphorylation state of a protein isolated in small
      quantities from a biological sample remains far from routine.

PMID- 11578936
TI  - Multiphoton microscopy in biological research.
AB  - From its conception a decade ago, multiphoton microscopy has evolved from a
      photonic novelty to an indispensable tool for gleaning information from
      subcellular events within organized tissue environments. Its relatively deep
      optical penetration has recently been exploited for subcellularly resolved
      investigations of disease models in living transgenic mice. Its enhanced spectral
      accessibility enables aberration-free imaging of fluorescent molecules absorbing
      in deep-UV energy regimes with simultaneous imaging of species having extremely
      diverse emission spectra. Although excited fluorescence is the primary signal for
      multiphoton microscopy, harmonic generation by multiphoton scattering processes
      are also valuable for imaging species with large anharmonic modes, such as
      collagen structures and membrane potential sensing dyes.

PMID- 11578937
TI  - A microfluidics platform for cell fusion.

PMID- 11578938
TI  - [Cyclin D1 and breast cancer: the good news of summer 2001].

PMID- 11578939
TI  - [The biopsy: a neologism coined by Ernest Besnier].

PMID- 11578940
TI  - [Angiogenin: involvement in angiogenesis and tumour growth].
AB  - Angiogenin is one of the most potent inducers of neovascularization in
      experimental models in vivo. Angiogenin is normally present in plasma but
      overexpressed in cancer patients. The possible involvement of angiogenin in the
      development of cancer is suggested by its overexpression in patients with a
      variety of tumours and the observation that angiogenin antagonists prevent the
      growth of human tumour xenografts in athymic mice. This 14.1-kDa protein has 35%
      amino acid sequence identity with human pancreatic ribonuclease and displays
      ribonucleolytic activity. As only angiogenin is able to induce angiogenesis, its
      biological activities are thought to result from structural characteristics.
      Although the structural characteristics of angiogenin have been extensively
      studied, the understanding of its physiological role and of how its properties
      are expressed is still to be deciphered. This article reviews some of the
      biological, biochemical and structural properties of angiogenin.

PMID- 11578941
TI  - [Technological advances in immuno-oncology: from fundamental concepts to patient
      immunological monitoring].
AB  - Over the past decade, cancer immunology has known several advances due to both
      basic research and new technologies recently developed in this field. This review
      will illustrate the impact of some new immunological technologies and how the
      latter resulted in the exploration of new territories in cancer immunology and
      the emergence of new concepts that allowed to revisit the immunosurveillance
      concept and permitted to improve the patient monitoring.

PMID- 11578942
TI  - [Molecular abnormalities in epithelial ovarian tumors: present and future].
AB  - Ovarian cancer is the fourth most common cancer in women. Its pronostic is
      dreadful and, in spite of numerous studies, the steps of ovarian carcinogenesis
      are unclear. Histologically, three sub-types of ovarian tumors (benign,
      borderline and invasive) are distinguished, suggesting the existence of a
      continuum. However, as each sub-type presents its own biologic characteristics,
      the hypothesis of the progression of a pre-neoplastic precursor (benign or
      borderline tumor) into an invasive tumor is still open to discussion. Numerous
      molecular biological studies have been conducted on ovarian tumors, with the aims
      of identifying their molecular abnormalities and better understanding the process
      of ovarian carcinogenesis. Synthesis of the published data (concerning oncogene
      amplification and/or surexpression, loss of heterozygosity, tumor suppressor gene
      inactivation, microsatellite instability) shows that there are numerous
      abnormalities, confirming the heterogeneity and the complexity of these tumors.
      Hence, it remains very difficult to draw a scheme of ovarian carcinogenesis.
      Nevertheless, in a near future the new technology of laser microdissection may
      improve the quality of the results and the study of early ovarian lesions.
      Indeed, with this technique, it becomes possible to isolate well-defined and
      homogeneous cell populations and to study small or architecturally complex
      (surface lesions) tumors. In the next years, the results obtained may allow the
      identification of early events of the ovarian carcinogenesis and the development
      of diagnostic and therapeutic tools.

PMID- 11578943
TI  - [Epidemiology and costs of lung cancer in France].
AB  - There were 21,850 cases of newly diagnosed lung cancers in France in 1995. This
      figure corresponds to an incidence rate (standardized to the population of
      Europe) of 66.5 per 100,000 men and 8.9 per 100,000 women. The incidence is age
      related and reaches a peak between 70 and 74 years of age for men and between 75
      and 79 years of age for women. The incidence also varies by region and the
      highest rates were observed in east of France. Non-small-cell lung cancers
      represent 80% of all lung cancers. Between 1985 and 1995, as a result of changes
      in tobacco consumption, the incidence rates increased by 56% in women and by 5%
      in men under the age of 65. The incidence rates in France are close to the
      average rates observed in Europe. In 1995, lung cancers led to 23,900 deaths in
      France (mortality rate standardized to Europe: 36.6 per 100,000). 85% of deaths
      due to lung cancer occurred among men. Prognosis of lung cancer remains poor and
      has not improved appreciably over the last two decades. 58% of all patients died
      during the first year and 82% during the three years following lung cancer
      diagnosis. Survival rates appear to be better for patients with non small cell
      lung cancer than for patients with small cell lung cancer. Few studies have
      addressed the economics of lung cancer in France. Cost-of-illness studies of lung
      cancer were published mainly in Canada, the Netherlands and Australia. These
      analyses have included descriptive works as well as economic models based on
      theoretical diagnostic and treatment algorithms.

PMID- 11578944
TI  - [Economic assessments of head and neck cancers: a review].
AB  - The aim of this study is to perform a review of the literature on economic
      studies in the area of head and neck cancer (including the cancers of the buccal
      cavity, the larynx, and the pharynx). French and international literature (as
      reported on Medline and OHE-IFPMA databases) has been reviewed. This research
      demonstrated the lack of economic data in this field. In France, only one study
      was found, assessing the cost of the treatment of head and neck cancer in
      hospital to 29 billions French Francs including 2.3 billions linked to head and
      neck cancer. This relative indifference is possibly due to the heterogeneity and
      the low incidence of the studied pathologies. In addition, the research
      highlighted the great interest of dealing with quality of life in such physically
      and psychologically disabling illnesses. To facilitate the decision making and to
      allow optimal resource allocation in the area of costly health strategies, we
      should develop in France an economic evaluation of the head and neck cancer,
      while taking care of integrating the notion of quality of life into the analysis.

PMID- 11578945
TI  - [Standards, options and recommendations: practice guidelines for difficult
      diagnosis in surgical pathology or cytopathology in cancer patients].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in
      1993 is a collaboration between the Federation of the French Cancer Centres
      (FNCLCC), the 20 French Cancer Centres and specialists from French Public
      Universities, General Hospitals and Private Clinics. The main objective is the
      development of clinical practice guidelines to improve the quality of health care
      and outcome for cancer patients. The methodology is based on literature review
      and critical appraisal by a multidisciplinary group of experts, with feedback
      from specialists in cancer care delivery. OBJECTIVES: To develop clinical
      practice guidelines according to the definitions of the Standards, Options and
      Recommendations project for difficult diagnoses in surgical pathology or
      cytopathology in cancer patients. METHODS: Data were identified by searching
      Medline and using the personal reference lists of members of the expert groups.
      Once the guidelines were defined, the document was submitted for review to 71
      independent reviewers. RESULTS: The main recommendations to prevent and reduce
      the number of difficult diagnoses in surgical pathology or cytopathology are: 1)
      The development of quality insurance programs with use of written procedures in
      each pathology laboratory (standard). 2) The knowledge of clinical data in order
      to explain surgical pathology or cytopathology results (standard). 3) The
      availability of complementary patient informations (radiologic data . . .) can be
      useful to explain surgical pathology or cytopathology results (option). The main
      recommendations to detect lesions associated with difficult diagnosis in surgical
      pathology or cytopathology are: 1) Tumor types known as potential difficult
      diagnosis in surgical pathology or cytopathology should be reviewed by a second
      pathologist. 2) The systematic second reviewing for every case is expensive but
      has to be done when the difficulty is know (sarcoma, lymphoma . . .) by
      experienced pathologists. The main recommendations to solve difficult diagnosis
      in surgical pathology or cytopathology are: 1) Block recuts, use of special
      techniques (immunocytohistochemistry and molecular biology), additional data from
      clinicians, second opinion by a local pathologist, or new specimen can be
      required for establishing the diagnosis (options). 2) Outside second opinion by
      expert pathologist has to be considered once the other steps did not allow to
      establish surgical or cytopathology diagnosis (recommendations, expert
      agreement).

PMID- 11578946
TI  - [Standards, options and recommendations for blood tumor markers in thyroid
      cancers].
AB  - CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in
      1993, is a collaboration between the Federation of the French Cancer Centers
      (FNCLCC), the 20 French Cancer Centers and specialists from French Public
      Universities, General Hospitals and Private Clinics. The main objective is the
      development of clinical practice guidelines to improve the quality of health care
      and outcome for cancer patients. The methodology is based on literature review
      and critical appraisal by a multidisciplinary group of experts, with feedback
      from specialists in cancer care delivery. OBJECTIVES: To define, according to the
      definitions of the Standards, Options and Recommendations project, the
      characteristics of the main tumor markers in thyroid cancer and the potential
      role of these markers in the management of patients with this malignancy.
      METHODS: Data were identified by searching Medline and the personal reference
      lists of members of the expert groups. Once the guidelines were defined, the
      document was submitted for review to 55 independent reviewers, and to the medical
      committees of the 20 French Cancer Centers. RESULTS: The main recommendations
      are: 1) Thyroglobulin is a serum tumor marker for the monitoring of operated
      thyroid differentiated neoplasms (standard). 2) It is essential to know if the
      patient is under TSH stimulation or under thyroid suppression therapy to
      interpret thyroglobulin results (standard). 3) Thyroglobulin assay must be
      performed regularly during the monitoring of differentiated thyroid neoplasms
      (standard, level of evidence B2), should be coupled with the measurement of anti
      thyroglobulin antibodies concentration using a sensitive method (standard, level
      of evidence B2). 4) Thyroglobulin assay should not be performed to detect or
      diagnose differentiated thyroid neoplasms (standard, level of evidence B2). 5)
      The methods used to assay thyroglobulin must have a limit of detection lower than
      3 mug.l- 1 (standard, expert agreement). 6) Calcitonin is a marker for medullary
      thyroid cancer (standard). 7) Its assay, associated with RET gene study if
      indicated, enables medullary thyroid cancer to be diagnosed. 8) The pentagastrin
      test is essential to diagnose familial forms of medullary thyroid cancer. 9) All
      analyses for each patient must be performed in the same laboratory, using the
      same technique (standard, expert agreement). 10) Calcitonin and carcinoembryonic
      antigen are serum markers for the monitoring of medullary thyroid cancer and
      allow the detection of recurrent disease (standard).

PMID- 11578947
TI  - [Assessing the quality of patients' medical records at the Claudius-Regaud
      Institute].
AB  - In 1999, the Claudius-Regaud Institute of Toulouse, France, specialized in
      oncology, set up a workshop in order to assess the quality of its patients
      medical records. A retrospective evaluation was performed on a 100-chart-sample
      drawn from all the charts in the institution. Results show that the medical
      records are subdivised into three parts: medical care, nursing care and imaging.
      Some of the explored charts show a lack of data, and a certain inconsistency in
      the charts' organization and in the structure of information was reported.
      Patient's record is a key to communication between the different care providers
      in oncology. To improve its quality, efforts will have to be done in
      restructuring the charts, creating guidelines and training the different
      caregivers.

PMID- 11578948
TI  - [Statistical analysis of a prognostic study].
AB  - Prognostic studies aim to stress and quantify the effect of some individual
      characteristics on the evolution of an illness. Statistically speaking, most of
      the time, a prognostic study relying on a censored endpoint can be summarized in
      building a Cox model. Even though they are often encountered in clinical research
      or in epidemiology, prognostic studies are rarely reliable and there is no real
      consensus on the way to perform them. The aim of this article is to give some
      directions regarding the analysis of such studies. For illustration purpose, this
      paper relies on commented results from a study in oncology.

PMID- 11578951
TI  - Detection of TNF inhibitors (soluble receptors) in the sera and tumor cyst fluid
      of patients with malignant astrocytomas of the brain.
AB  - Patients with malignant astrocytomas of the brain exhibit varying degrees of
      immunosuppression with only a few factors responsible for this immunosuppression
      having been characterized. The soluble forms of the 55 kDa and 75 kDa membrane
      receptors for tumor necrosis factor (sTNF-R's) have been shown to bind to and
      inhibit the activity of TNF. The present studies analyze levels of sTNF-R's in
      the sera and tumor cyst fluids of patients with malignant astrocytomas. Using
      sensitive ELISA techniques, serum levels of the 55 and 75 kDa sTNF-R's in 17
      patients tested were found to be elevated (55 kDa of 2.29 ( 2.85 ng/ml and 75 kDa
      of 4.98 ( 4.03 ng/ml( as compared to 20 normal controls (55 kDa of of 1.21 ( 0.91
      ng/ml and 75 kDa of 1.85 ( 0.40 ng/ml( although this was only statistically
      significant for the 75 kDa sTNF-R (P=0.006). Brain tymor cyst fluid samples
      obtained from eight patients were shown to have very high levels of both sTNF-R's
      ranging from 4.16 to 17.17 ng/ml for the 55 kDa receptor and 4.83 to 19.96 ng/ml
      for the 75 kDa receptor. Six of these cyst fluid samples were also tested for
      their ability to inhibit TNF cytolytic activity using an in vitro assay. All
      samples tested had TNF inhibitory activity. Immunohistochemical studies on
      patient tumor samples showed high levels of expression of these receptors both in
      the cytoplasm and the cell surface of astrocytoma cells. We propose that sTNF-R's
      may be shed by astrocytoma cells and may have a role in both local and systemic
      immunosuppression observed in astrocytoma patients. Finally, the potential role
      of serum level of sTNF-R's as tumor markers to follow the treatment and the
      progression of disease in these patients are discussed.

PMID- 11578952
TI  - Getting into the groove: unusual features of peptide binding to MHC class I
      molecules and implications in vaccine design.
AB  - The major histocompatibility complex presents antigenic peptides on the surface
      of antigen presenting cells to T cell receptors. Recognition of peptide-MHC by T
      cells initiates a cascade of signals in T cells which maintains a T cell
      dependent immune response. An understanding of the how peptides bind to MHC class
      I molecules is an important prerequisite in the design of vaccines. Herein, we
      will discuss, with special emphasis on MUC1, unusual features of MUC1 peptide
      binding to MHC class I, obtained from vaccine studies including a MUC1 peptide
      mimic and the crystal structures of low and high affinity peptides lacking
      canonical anchor motifs in complex with H-2Kb.

PMID- 11578953
TI  - Regulation of mucin and glycoconjugate expression: from normal epithelium to
      gastric tumors.
AB  - Gastric epithelium is protected by a mucus layer rich in MUC5AC and MUC6 mucins
      synthesised by the superficial epithelium and the glands, respectively. These
      cell populations also express specific fucosyltransferases that determine the
      glycosylation pattern of these gastric mucins. The maintenance of the structure
      and properties of the gastric mucus has been related to the degree of
      glycosylation and the oligomeric forms of the mucins. In gastric tumors, and in
      early preneoplastic lesions such as intestinal metaplasia, the glycosylation
      pattern detected in normal stomach is lost and, intestinal mucins, MUC2 and MUC4,
      can be ectopically detected in the gastric epithelium. These changes are
      biologically relevant because the binding of Helicobacter pylori to the gastric
      mucosa is mediated by blood group-related antigens. In vitro and animal models
      allowing the study of the gastric ecological niche and the requirements for its
      maintenance are essential for an understanding of the role of bacterial-mucosal
      interactions in pathological processes such as inflammation and cancer.

PMID- 11578954
TI  - Role of Muller cells in retinal degenerations.
AB  - Muller (radial glial) cells span the entire thickness of the retina, and contact
      and ensheath every type of neuronal cell body and process. This morphological
      relationship is reflected by a multitude of functional interactions between
      retinal neurons and Muller cells, including extracellular ion homeostasis and
      glutamate recycling by Muller cells. Virtually every disease of the retina is
      associated with a reactive Muller cell gliosis. Muller cell gliosis may either
      support the survival of retinal neurons or accelerate the progress of neuronal
      degeneration. Muller cells are key mediators of nerve cell protection, especially
      via release of basic fibroblast growth factor, via uptake and degradation of the
      excitotoxin glutamate, and via secretion of the antioxidant glutathione.
      Neovascularization during hypoxic conditions is mediated by Muller cells via
      release of vascular endothelial growth factor and transforming growth factor beta
      or via direct contact to endothelial cells. Primary Muller cell insufficiency has
      been suggested to be the cause of different cases of retinal degeneration
      including hepatic and methanol-induced retinopathy and glaucoma. It is
      conceivable that, in the future, new therapeutic strategies may utilize Muller
      cells for, e.g., somatic gene therapy or transdifferentiation of retinal neurons
      from dedifferentiated Muller cells.

PMID- 11578955
TI  - Surgical implications of Helicobacter pylori infection.
AB  - Helicobacter pylori infection is the most common cause of peptic ulcer disease
      and is an etiologic factor in the development of gastric malignancies.
      Eradication of H. pylori heals most uncomplicated peptic ulcers, as well as
      preventing their relapse. In addition, H. pylori therapy has recently been used
      as a first line treatment for most low grade MALT lymphomas. Despite its
      efficacy, a small percentage of patients with peptic ulcer disease will require
      operative intervention and the indications for surgical intervention for the
      patient with peptic ulcer disease include; intractability, gastric outlet
      obstruction, acute perforation, and bleeding uncontrolled by endoscopic
      intervention. H. pylori has also been shown to be associated with an increased
      risk of gastric adenocarcinoma and surgical exploration may play a role in
      diagnosis, staging and treatment. Finally, the relationship between H. pylori
      infection and the development of gastric MALT lymphoma is well established. While
      treatment for H. pylori infection is indicated for low grade MALT lymphomas,
      surgical resection may be indicated for treatment failures, as well as for
      certain high grade lesions.

PMID- 11578956
TI  - Intracellular signaling pathways: nongenomic actions of estrogens and ligand
      independent activation of estrogen receptors.
AB  - Recognition of the complexity of estrogen and estrogen receptor (ER) signaling
      has substantially increased in the last several years. In their genomic role,
      estrogens enter the cell and bind to ERs which are members of a superfamily of
      ligand-regulated transcription factors. However, estrogens also exert non-genomic
      effects that occur independently of gene transcription. Typically, these
      relatively rapid events are initiated at the plasma membrane, and result in the
      activation of intracellular signaling pathways. Regulation of ER transcriptional
      activity is also complex. Not only do ligands regulate ER-dependent gene
      expression, but this receptor in the apparent absence of its estrogenic ligand
      can also be transcriptionally activated by a variety of intracellular signaling
      pathways. Recent evidence also extends the effects of these signaling pathways to
      regulating the activity of coactivators, proteins which bind to the ER and
      amplify its transcriptional activity. Taken together, it is clear that estrogens,
      ERs and intracellular signaling pathways are intimately linked and this review
      will explore the relationship between these components of the estrogen-ER signal
      transduction process.

PMID- 11578957
TI  - Normal respiratory mucosa, precursor lesions and lung carcinomas: differential
      expression of human mucin genes.
AB  - Mucins are glycoproteins synthesized by epithelial cells and thought to promote
      tumor-cell invasion. Eight human mucin genes have been well characterized: MUC2,
      MUC5AC, MUC5B, MUC6 map to 11p15.5 and encode secretory gel forming mucins while
      MUC1, MUC3, MUC4, MUC7 are scattered on different chromosomes and encode membrane
      bound or secreted mucins. The expression pattern of the mucin genes is complex in
      normal airways involving six genes, mainly MUC5AC and MUC5B in mucus-producing
      cells and MUC4 in a wide array of epithelial cells. MUC5AC overexpression in
      metaplasia, dysplasia and normal epithelium adjacent to squamous cell carcinoma
      provides additional arguments for a mucous cell origin of preneoplastic squamous
      lesions. MUC5AC and MUC5B expression is related to mucus formation in
      adenocarcinomas. Mucinous bronchioloalveolar carcinoma (BAC) has a particular
      pattern of mucin gene expression indicating that it has sustained a well
      differentiated phenotype similar to the goblet cell, correlated with distinctive
      features i.e. a noninvasive pattern and a better prognosis than nonBACs. MUC4 is
      the earlier mucin gene expressed in the foregut, before epithelial
      differentiation and is expressed independently of mucus secretion both in normal
      adult airways and carcinomas. These findings are in favor the histogenetic theory
      of non-small-cell carcinoma originating from a pluripotent mucous cell.

PMID- 11578958
TI  - Mucins in the gastrointestinal tract in health and disease.
AB  - Mucins form part of the dynamic, interactive mucosal defensive system active at
      the mucosal surface of the gastrointestinal tract. They are carbohydrate rich
      glycoproteins with unique molecular structure and chemical properties. The family
      of mucin (MUC) genes has 13 members that can be divided into secreted and
      membrane-associated forms each with characteristic protein domains and tissue
      specific glycosylation. Biosynthetic pathways have been described for the
      secreted and membrane-associated mucins and their eventual degradation and
      turnover. Mucins are present at all mucosal surfaces throughout the body in
      typical combinations and relate to the demands of organ function. Patterns of MUC
      gene expression with gastrointestinal site specific glycosylation are clearly
      important but are not yet well defined. Mucin production during fetal development
      shows distinct patterns that may correlate in many cases with neoplastic
      expression in adult life. An increasing number of protective proteins have been
      identified that appear in the adherent mucus layer at the mucosal surface. These
      proteins are co-secreted with mucins in some cases, interact with mucins at a
      molecular level through peptide and carbohydrate sites or benefit from the
      viscoelastic, aqueous environment afforded by the mucus gel to effect their
      defensive roles. The mechanism of many of these interaction remains to be
      elucidated but is clearly part of an integrated innate and adaptive mucosal
      defensive system relying on the mucins as an integral component to provide a
      mucus gel. Recent improvements in the description of MUC gene expression and
      mature mucin synthesis in the healthy gastrointestinal tract has formed a basis
      for assessment of mucosal disease at sites throughout the tract. Pathological
      patterns of mucin expression in disease appear to follow tissue phenotype, so
      that gastric and intestinal types can be defined and appear in metaplasia in e.g.
      esophagus and stomach. Adaptation of previous mucin based, histochemical
      classification of intestinal metaplasia to assess MUC gene expression has proved
      helpful and promises greater value if reliably combined with mucin linked
      glycosylation markers. Few changes in MUC gene expression or polymorphism have
      been detected in inflammatory bowel diseases in contrast to malignant
      transformation. Glycosylation changes however, are evident in both types of
      disease and appear to be early events in disease pathogenesis. Review of the
      major mucosal diseases affecting the gastrointestinal tract in childhood reveals
      parallel patterns to those found in adult pathology, but with some novel
      conditions arising through the developmental stages at lactation and weaning. The
      impact of bacterial colonization and nutrition at these stages of life are
      important in the evaluation of mucosal responses in pediatric disease.

PMID- 11578959
TI  - Polymorphism of the human muc genes.
AB  - Mucins encoded by the MUC genes share the common feature of having an extensive
      tandem repeat region that encompasses a large proportion of the coding sequence.
      In many of the genes this tandem repeat region shows a great deal of allelic
      length variation and recently studies have demonstrated person to person
      variation in pattern of nucleotide or amino-acid changes in the repeat units. The
      length and sequence variability will be discussed in this review, as will its
      role in disease susceptibility.

PMID- 11578960
TI  - Mucins of the human endocervix.
AB  - The physical character and amount of mucus secreted by the endocervix changes
      dramatically at midcycle to facilitate the reproductive process. Mucins expressed
      by the endocervical epithelium contribute to this all-important physiologic
      event. This review summarizes work from our laboratory demonstrating the mucin
      gene expression profile of cervical epithelium and mucin levels in cervical mucus
      through the menstrual cycle. mRNA levels of the gel-forming mucin MUC5B, the
      major gel-forming mucin expressed by the endocervical epithelium, peak before
      midcycle and the amount of MUC5B protein per unit total protein in cervical mucus
      peaks at midcycle. Message levels for MUC4, a major membrane-spanning mucin of
      the endocervix, peak at midcycle, but protein levels of MUC4 in human cervical
      mucus have not been measured. Message for each mucin diminishes dramatically as
      progesterone levels increase in the blood. These data suggest hormonal regulation
      of the two mucin genes in the endocervix, but there is no information on their
      regulation at the biosynthetic level via genomic hormone response elements.
      Perhaps, through its hydrophilicity, the MUC5B mucin holds water in place at the
      endocervical canal surface at midcycle, keeping the canal patent for sperm
      motility. A second potential role of the increased mucins at midcycle is to
      protect the cervix and uterus at the time when increased water is secreted into
      the cervical canal to facilitate sperm penetrance. Pathogens and other seminal
      fluid components may be excluded from entering the uterus by mucin trapping.
      Studies to determine the mechanism of hormonal regulation of mucins as well as
      the function of individual mucins are needed.

PMID- 11578961
TI  - Inhibition of the glycosylation and alteration in the intracellular trafficking
      of mucins and other glycoproteins by GalNAcalpha-O-bn in mucosal cell lines: an
      effect mediated through the intracellular synthesis of complex GalNAcalpha-O-bn
      oligosaccharides.
AB  - To address the function of carbohydrates in mucins, GalNAcalpha-O-bn has been
      used in in vivo experiments on several human mucosal cultured cells as a
      potential competitor of the glycosylation of N-acetylgalactosamine residues.
      GalNAcalpha-O-bn is metabolized by glycosyltransferases expressed in the cell,
      and give rise to different internal derivatives starting in particular from the
      formation of the disaccharide Galalpha1-3GalNAcalpha-O-bn. In this line,
      GalNAcalpha-O-bn exposure inhibits peripheral glycosylation according a cell-type
      specific manner. The metabolic alterations are very important in HT-29 cell line,
      leading to a massive accumulation of GalNAcalpha-O-bn oligosaccharide derivatives
      and to a strong inhibition of the terminal elongation of O-glycans by alpha2,3
      sialyltransferase ST3Gal I. GalNAcalpha-O-bn treatment also induced alterations
      at the cellular level, exhibiting a large scale in HT-29 cells, i.e. 1) an
      inhibition of mucin secretion, 2) a blockade in the targeting of some membrane
      glycoproteins (brush border glycoproteins such as dipeptidylpeptidase IV,
      carcinoembryonic antigen and the mucin-like glycoprotein MUC1, and the
      basolateral cell adhesion molecule CD44), 3) an inhibition in the processing of
      lysosomal enzymes. Morphological abnormalities have been evidenced in GalNAcalpha
      O-bn treated cells, in particular the accumulation of numerous intracellular
      vesicles in HT-29 cells. Taken together, these data suggest that O-glycosylation
      might be involved in the regulation of the targeting of O-glycosylproteins
      through carrier vesicles.

PMID- 11578962
TI  - T cells in the pathogenesis of systemic lupus erythematosus.
AB  - The role of T cells in the pathogenesis of systemic lupus erythematosus (SLE) is
      reviewed with a focus on autoantigen-specific T cells in SLE. The initial clue to
      a role for T cells in SLE was histopathologic studies demonstrating extensive
      infiltration of T cells at the sites of inflammation. Later studies, showing
      association between HLA polymorphisms and specific autoantibodies, directly
      implicated a role for T cells in autoantibody production. More recently, we and
      others have identified and characterized autoantigen-specific T cells in SLE. We
      review these studies on the role of autoantigen-specific T cells in SLE and
      present new findings on the molecular characterization of T cell immunity to Sm
      B, Sm-D and U1-70kD small nuclear ribonucleoprotein (snRNP) autoantigens.

PMID- 11578963
TI  - Germ cell nuclear factor is a transcriptional repressor essential for embryonic
      development.
AB  - GCNF is an orphan member of the nuclear receptor superfamily. The nuclear
      receptor superfamily is a large superfamily of transcription factors, the
      majority of which are designated as orphan receptors because their ligands and
      functions are currently unknown. GCNF (Germ Cell Nuclear Factor) is so named
      because of its restricted expression pattern in the adult. In the testis, GCNF is
      expressed only in the post meiotic round spermatids. Likewise in the ovary,
      GCNF's expression is restricted to the growing oocyte. To date nothing is known
      of GCNF's putative ligand; however, much is known about its physiological
      function through the use of gene targeting. Inactivation of the GCNF gene showed
      that it was essential for normal embryonic development. In addition to being
      expressed in the germ cells of the adult, it is expressed widely throughout the
      embryo after gastrulation. Significant strides have also been made in
      understanding GCNF's mechanism of action using molecular biology. The DNA binding
      properties of GCNF have been investigated and its response element identified.
      GCNF binds as a homodimer to a direct repeat element with zero nucleotides
      between the reiterated sequence AGGTCA. GCNF target genes have been identified
      that contain this DR0 element in their promoters. Such genes as Protamines 1 and
      2 and Oct4 are regulated by GCNF through this element. GCNF has been shown to be
      a repressor of the protamine and Oct4 genes. GCNF's repression function has been
      shown to be mediated by interaction with the co-repressors N-CoR and SMRT in the
      absence of ligand. Our current efforts are to explore GCNF function in the adult
      germ cells using tissue specific gene targeting to specifically knock out the
      GCNF gene in oocytes and spermatogenic cells. In addition, efforts are being made
      to identify the endogenous ligand that regulates GCNF's transcriptional
      properties.

PMID- 11578964
TI  - Mucins in protozoan parasites.
AB  - Studies on host-pathogen interactions have led to the discovery of various cell
      surface associated and secretory molecules. Mucins and mucin-like molecules have
      recently been described in several protozoan parasites, at different stages of
      the life cycle. These share many structural and compositional features with
      mammalian mucins, but vary in several other aspects. It is now becoming evident
      that mucins in parasite are involved in cell-cell interaction and cell surface
      protection, thus helping the parasite to establish infection. A large number of
      mucin like genes from the parasite genome have been reported, and their
      expression differ during the developmental stages of the parasite. In this
      review, we describe the structure and functions of mucin and mucin-like molecules
      in parasitic protozoa.

PMID- 11578965
TI  - Testing for Helicobacter pylori in the clinical setting.
AB  - There are a variety of tests available to identify Helicobacter pylori infection.
      These tests can be divided into those that do not require and those that do
      require endoscopy. This review provides a detailed discussion of the available
      diagnostic tests for H. pylori infection. Special attention is paid to the role
      of diagnostic testing in the management of patients with H. pylori-related
      disease. The potential advantages and disadvantages of various tests and the role
      of testing to confirm eradication after treatment for H. pylori is also
      discussed.

PMID- 11578966
TI  - Pathophysiology of gallstone pancreatitis.
AB  - Gallstone pancreatitis was first recognized as an entity by Opie in 1901 (1), and
      since then has generated volumes of literature which have attempted to explain
      its pathophysiology. Multiple animal experiments and human clinical studies in
      the past thirty years have led to a better understanding of both macro- and
      microscopic events which lead to pancreatic inflammation in the setting of a
      passing or impacted gallstone. Evidence suggests that pancreatic duct outflow
      obstruction is the initial event. Several possible sequelae of duct obstruction,
      including refluxed biliary-pancreatic secretions, pancreatic duct hypertension,
      and/or aberrant acinar cell secretion may result in pancreatic duct injury and
      release of pancreatic enzymes into the glandular interstitium, thus triggering a
      bout of acute pancreatitis. The details of many events related to gallstone
      pancreatitis remain unclear; this chapter attempts to present the pathophysiology
      of this disease as it is known today. Additionally, clinical presentation and
      treatment of gallstone pancreatitis will be reviewed briefly.

PMID- 11578967
TI  - Control of RNA polymerase II activity by dedicated CTD kinases and phosphatases.
AB  - The elongation phase of eukaryotic transcription by RNA polymerase II (RNAPII) is
      an important target for regulation of gene expression. An interplay of positive
      and negative elongation factors determines the elongation activity of RNAPII in
      different promoters. The phosphorylation status of the carboxyl-terminal-domain
      (CTD) of the larger subunit of RNAPII appears to be the regulatory focus of
      different factors regulating mRNA processivity. The emerging model of the
      transcription cycle proposes that the phosphorylation state of the CTD is dynamic
      during elongation with different forms predominating at different stages of
      transcription. Shortly after initiation RNA polymerase II comes under the control
      of negative elongation factors and enters abortive elongation. Escape from the
      action of these negative controls requires the action of at least one positive
      elongation factor identified in the P-TEFb complex composed of the Cyclin
      Dependent Kinase CDK9 and its regulatory subunit cyclin T. Finally, the
      requirement of CTD phosphatase activity, identified in the FCP1 protein, has been
      invoked as necessary to recycle the hypophosphorylated form of the RNA polymerase
      II competent to reinitiate the transcription cycle.

PMID- 11578968
TI  - The role of Epstein-Barr virus in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a devastating autoimmune disease with no
      known cure. Lupus patients suffer from a myriad of clinical symptoms which
      variably include arthritis, pleuritis, pericarditis, vasculitis, and nephritis.
      The underlying mechanisms behind these clinical findings and the etiologic events
      preceding and causing disease onset, however, remain largely unknown. For many
      years, investigators have suspected that Epstein-Barr virus might somehow be
      involved in the etiology and/or pathogenesis of systemic lupus. Numerous studies
      have examined this possibility from various angles and have arrived at different
      conclusions. This work reviews these historical papers in the context of new
      results and presents a hypothetical role for this virus as an etiological
      environmental trigger for SLE.

PMID- 11578969
TI  - Structural organization and classification of the human mucin genes.
AB  - The cells of living organisms in contact with the external environment are
      constantly attacked by different kinds of substances such as micro-organisms,
      toxins, and pollutants. With evolution, defense mechanisms, such as the secretion
      of mucus has been developed. Mucins are the main components of mucus. They are
      synthesized and secreted by specialized cells of the epithelium and in some case,
      by non mucin-secreting cells. Little was known about the structure of mucins
      until a decade ago. This is principally due to heavy glycosylation of mucins,
      which complicated their analysis. With the application of molecular biological
      methods, structures of the mucin core peptides (apomucins) are beginning to be
      elucidated. A total of eleven human mucin (MUC) genes have been identified and
      numbered in chronological order of their description: MUC1-4, MUC5AC, MUC5B, MUC6
      8, and MUC11-12. Of these, the complete cDNA sequence are published only for six
      mucins MUC1, MUC2, MUC4, MUC5B, MUC5AC, and MUC7. Human mucin genes, in general,
      show three common features: I) a nucleotide tandem repeat domain; II) a predicted
      peptide domain containing a high percentage of serines and threonines; III)
      complex RNA expression. The tandem repeats in mucins make up the majority of the
      backbone. Related to their structure, mucins can be classified in three distinct
      sub-families: gel-forming, soluble, and membrane-bound. Each member from one
      family possesses common characteristics and probably specific functions. For a
      long time, they were thought to have the unique function of protecting and
      lubricating the epithelial surfaces. The study of the mucins structure as well as
      the relationship between structure and function show that mucins also possess
      other important functions, such as growth, direct implication in the fetal
      development, the epithelial renewal and differentiation, the epithelial
      integrity, carcinogenesis, and metastasis. This review presents the actual
      knowledge on the mucins structure and the best-characterized function related to
      their structure.

PMID- 11578970
TI  - Tools for predicting risk of mortality in the ICU setting: do we need a crystal
      ball or rose colored glasses?
AB  - Hematopoietic stem cell transplantation (HSCT) applied to children is associated
      with high risk for organ failure, ICU admission, morbidity and mortality.
      "Respiratory failure" after HSCT carries a historically grave prognosis. Factors
      associated with high risk for critical care complications in HSCT patients have
      been identified, but are dependent on timing and intensity of interventions.
      Several ICU severity of illness scoring systems predict prognosis on the basis of
      physiologic stability, organ system involvement, and intensity of supportive
      measures; but these tend to underestimate post-transplantation mortality risk.
      Adjustment of scoring systems and logistic regression factor analysis are
      promising adjuncts, but have not been adequately validated. Specific endpoints
      such as death, length of ICU or hospital stay, and neurologic function are
      relatively easy to quantify; but, quality of life is difficult to assess and
      report. What constitutes "heroic therapy" in one institution may qualify as
      "routine" care in another. Therefore, tools to predict mortality in the pediatric
      HSCT recipient requiring intensive care are difficult to apply to the individual
      patient, and remain more an art than science. This manuscript attempts to briefly
      define and review the pertinent types of PICU severity of illness and mortality
      prognosis scoring systems, and their application to pediatric HSCT patients.
      Pitfalls in application of physiology, organ system failure, therapeutic
      intensity, disease specific, and history-based scoring systems are discussed.
      Prospective validation studies for severity of illness systems and the evolution
      to concurrent registry-style data collection and analysis are necessary for the
      HSCT patient requiring ICU care.

PMID- 11578971
TI  - Developmental history of the mammalian oocyte: insight from mouse mutations.
AB  - Growth and differentiation of the mammalian oocyte is regulated with the
      coordinate development of the granulosa cells. The complex signaling pathways
      that regulate the growth and development of mammalian oocytes are beginning to be
      elucidated through the use of gene targeting. These technologies have provided
      new insight into the roles of specific genes during the development of the germ
      cells and gonads, as well as post-pubertal development of oocytes. In many cases,
      these studies have resulted in a new understanding of the function of certain
      genes, in others they have provided new genes and pathways to be studied in
      mammalian reproductive biology. Ultimately, these studies will shed light on
      human genetic disease and infertility.

PMID- 11578972
TI  - Receptor for age (RAGE) is a gene within the major histocompatibility class III
      region: implications for host response mechanisms in homeostasis and chronic
      disease.
AB  - Receptor for AGE (RAGE), a member of the immunoglobulin superfamily, was first
      identified as a specific cell surface interaction site for Advanced Glycation
      Endproducts, or AGEs. AGEs, the products of nonenzymatic glycation/oxidation of
      proteins/lipids, accumulate in natural aging and disorders such as diabetes,
      renal failure and amyloidoses. Interaction of AGEs with RAGE has been linked to
      chronic inflammatory and vascular dysfunction that characterizes the chronic
      complications of these disorders. Recent studies have indicated that RAGE is a
      multiligand receptor, serving as a specific cell surface, signal transducing
      receptor for amphoterin, a molecule with implications for neurite outgrowth in
      neuronal development and in tumor cell proliferation and spread. RAGE is also a
      receptor for amyloid-beta peptide, whose interaction with neuronal and microglial
      RAGE within the CNS is linked to sustained inflammation and neuronal toxicity and
      cell death. RAGE also serves as a signal-transducing receptor for EN-RAGEs, and
      related members of the S100/calgranulin family of proinflammatory cytokines;
      consequences of this interaction include initiation and propagation of
      inflammatory responses. Consistent with an important role for ligand-RAGE
      interaction in these settings, blockade of RAGE suppresses chronic cellular
      activation and dysfunction in murine models of diabetic complications,
      inflammation and tumor proliferation and metastasis. Taken together, an new
      paradigm is emerging which links RAGE, a gene encoded within the Major
      Histocompatibility Complex (MHC) Class III regions, to central host response
      mechanisms in homeostasis and chronic disease.

PMID- 11578973
TI  - Transcriptional regulation of the 11p15 mucin genes. Towards new biological tools
      in human therapy, in inflammatory diseases and cancer?
AB  - Mucin production and secretion by specialized epithelial cells is a common
      mechanism used by mammals to protect the underlying mucosae against various
      injuries (pollutants, pathogens, pH). The expression of mucin genes is cell- and
      tissue-specific but is submitted to variations during cell differentiation,
      inflammatory process, and is altered during carcinogenesis. The molecular
      mechanisms responsible for the control of mucin transcription and expression are
      beginning to be understood as mucin gene promoters and regulatory regions are
      characterized. The four gel-forming mucin genes, MUC2-MUC5AC-MUC5B-MUC6, are
      clustered on the p15 arm of chromosome 11. Common regulatory mechanisms (PKA,
      PKC, PKG and Ca2+ signaling, Sp1/Sp3) may account for the capability of mucous
      secreting cells to express several mucin genes simultaneously. In response to an
      insult or during carcinogenesis, the normal pattern of expression is altered and
      results from specific answers of the cell by activating different intracellular
      signaling pathways. 11p15 mucin genes are regulated at the transcriptional level
      by pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha), pleiotropic cytokines
      (IL-4, IL-13, IL-9), bacterial exoproduct (LPS), growth factors (EGF, TGF-alpha),
      lipid mediator (PAF), retinoids and hormones. To date, the only downstream
      cascade known to activate mucin gene transcription is the Src/Ras/MAPK/pp90rsk
      cascade, which leads to the activation of the transcription factor NF-kappaB.
      Mucin gene transcription is also regulated by ATF-1, CREB and RAR-alpha
      transcription factors. Finally, repression of mucin transcription in cancer cells
      is under the control of the epigenetic mechanism of methylation. As
      transcriptional regulation of mucin genes begins to be unraveled, it becomes
      clear that many signaling pathways are involved. Our understanding of mucin gene
      transcriptional regulation, which awaits more data (identification of the
      signaling cascades and active cis-elements within promoters and introns), will
      most certainly lead to the use of mucin genes as molecular markers in cancer and
      molecular tools in human gene therapy, and to the synthesis of new therapeutic
      agents in inflammatory diseases of the epithelium.

PMID- 11578974
TI  - Role of the sigmoid colon in the defecation mechanism with evidence of sigmoido
      anal inhibitory and ano-sigmoid excitatory reflex.
AB  - In spite of voluminous literature that has been written on defecation, the exact
      mechanism has not yet been fully cleared up. The current study investigated the
      effect of sigmoid colon (SC) distension on anal motile activity and of anal
      distension on SC motility. Sixteen healthy volunteers (age 36.2 +/- 11.6 SD
      years, 10 men) were studied. The SC was distended by a balloon in 10 ml
      increments of CO2, and the anal, rectal and SC pressure response was recorded
      before and after their individual anesthetization. The anal, rectal and SC
      pressure response to anal distension in increments of 2 ml of CO2 was also
      registered. SC distension with big volumes (mean 86.2 +/- 1.9 ml) effected a SC
      pressure increase (p<0.05) and no rectal pressure response (p>0.05); the balloon
      was expelled to the exterior. Distension of the anesthetized SC caused no SC,
      rectal or anal pressure response (p>0.05, p>0.05, p>0.05, respectively); the
      response returned after the anesthetic effect had waned. SC distension while the
      rectum had been anesthetized, affected a significant SC pressure rise as well as
      an anal pressure decrease and balloon expulsion to the exterior. Anal balloon
      distension produced a significant pressure rise of the SC (p<0.001) and rectum
      (p<0.01). Distension of the anesthetized rectal neck (anal canal) caused no SC or
      rectal pressure response (p>0.05, p>0.05, respectively); response returned after
      the anesthetic effect had disappeared. SC distension appears to effect anal
      dilatation while anal distension causes SC contraction. This reciprocal action is
      suggested to be reflex and mediated through the "sigmoido-anal inhibitory reflex"
      and the "ano-sigmoid excitatory reflex". These 2 reflexes are believed to keep
      the SC contracting and the rectal neck dilated until complete SC evacuation
      occurs. The study seemingly negates the role of rectal distension as a
      prerequisite for balloon expulsion.

PMID- 11578975
TI  - Effects of H. pylori infection of gastric epithelial cells on cell cycle control.
AB  - Chronic infection of the gastric mucosa by the bacterium H. pylori results in an
      intense inflammatory response which can last for decades. An associated host
      response is a chronic hyperproliferative state, in which there is increased cell
      turnover and also increased apoptosis of the gastric epithelial cells. Recent
      studies have also demonstrated abnormalities in the expression of cell cycle
      control proteins. This review describes these events, emphasizing recent studies
      on the effects of H. pylori infection on cell cycle progression and the
      expression of cell cycle regulatory proteins. The systems that have been studied
      include in vivo studies in humans and in experimental animals, and in vitro
      studies in which gastric epithelial cells were co-cultivated with H. pylori. The
      earliest event following H. pylori's interaction with epithelial cells appears to
      be growth inhibition and apoptosis. The hyperproliferative response observed in
      the gastric mucosa is secondary to this initial insult and is associated with
      increased expression of cyclin D1, the cyclin dependent kinase inhibitor p16ink4a
      and of p53 and decreased expression of the cyclin dependent kinase inhibitor
      p27kip1. Dysregulation of the hyperproliferative response may, ultimately, be
      responsible for the ability of H. pylori to enhance the development of gastric
      cancer.

PMID- 11578976
TI  - The role of bacteria in gallstone pathogenesis.
AB  - Bacteria are often found in high concentrations in brown pigment and less so in
      cholesterol gallstones. Although it is intriguing to hypothesize that cholesterol
      stone formation is non-bacterial in nature and principally different from the
      pathogenesis of "infectious" brown pigment gallstones, it is more likely that
      significant overlap exists between the two processes. Most gallstones are
      composite in nature. Using molecular-genetic methods, bacteria can be found in
      most pure cholesterol gallstones (i.e. those whose structure consists of more
      than 90% cholesterol). The natural history of the gallstones development is
      unknown. It is likely that brown pigment stones can evolve in their chemical
      composition after the termination of the infectious process that initiate their
      formation, and may further develop into either mixed or nearly pure cholesterol
      stones. In a similar fashion, cholesterol-poor or black pigment gallstones may
      act as foreign bodies to enhance the propensity of bacterial colonization in the
      presence of pre-existing gallstones or cholangitis, thereby activating pathways
      of bacterial lithogenesis and resulting in the encasement of cholesterol nuclei
      with pigment shells and/or in the internal remodeling of extant stones. It is
      often difficult, if not impossible, to ascertain whether bacterial infection of
      bile arose before stone formation or vice-versa. The development of gallstones
      (nucleation, assembly of microcalculi, growth, remodeling) includes the
      interaction of both bacterial and non-bacterial mechanisms, working
      discontinuously over years and decades and shaping the structural individuality
      of each stone. At cholecystectomy, the gallstone removed from the patient
      represents the end product of a long pathologic process. Although our
      understanding of the exact temporal contribution of bacteria in lithogenesis is
      incomplete, it is important for the clinician to realize that most gallstones are
      colonized by a bacterial biofilm, even though the bile may be culture-negative.

PMID- 11578977
TI  - Nitric oxide: one of the more conserved and widespread signaling molecules.
AB  - After the discovery of the vasodilatory functions of nitric oxide (NO), many
      signaling mechanisms involving NO were identified through experiments on mammals.
      NO activates soluble guanylyl cyclase to induce the formation of cGMP, stimulates
      ADP-ribosylation of GAPDH to alter cell energy production, and combines with
      superoxide to generate peroxynitrite. It then became clear that NO was a major
      messenger molecule in mammals, involved in the regulation of blood vessel
      dilatation, immune function and neurotransmission in the brain and peripheral
      nervous system. The wide spectrum of physiological effects of NO in mammals
      prompted researchers to look for the presence of NO in vertebrates and
      invertebrates. Parallel findings on the presence of NO signaling in vertebrates
      and invertebrates were observed, and then NO was found to be a signaling molecule
      widely spread throughout the metazoan kingdom and whose functions were highly
      conserved during evolution. These features were extended to the entire animal
      kingdom after the discovery of NOS activity in protozoa, yeasts and bacteria.
      Recently, the involvement of NO and NOS in plant disease resistance to infection
      was documented and many close similarities were detected between NO-dependent
      signaling mechanisms involved in plants and those identified in animals. All of
      these results indicated that NO is one of the earliest and most widespread
      signaling molecules in living organisms. This short review was aimed at
      marshalling recent information that led to this conclusion.

PMID- 11578978
TI  - Mucin antibodies - new tools in diagnosis and therapy of cancer.
AB  - Many cancer and diseased cells are distinguished from their normal counterparts
      by an altered expression of cell-surface epitopes. One family of molecules that
      show altered expression on tumor cells is mucins (MUC). Unlike normal tissue
      where MUC exists as heavily glycosylated form, the disease- or tumor-associated
      MUC molecules are underglycosylated. Such underglycosylation of the core protein
      in cancer tissues exposes new epitopes on the cell surface that are unique to
      cancer tissues. Several monoclonal antibodies (Mabs) have been generated against
      these normal and tumor-associated mucins. Enzymatic fragments of Mabs like
      F(ab')2 and Fab have shown improved clinical utility for diagnosis, imaging, and
      therapy of cancer. Genetic-engineering methods have been used to design antibody
      fragments exhibiting high functional affinity, good tumor localization, and rapid
      clearance from the blood stream thus minimizing radiation exposure to the normal
      tissues. Such recombinant fragments have shown encouraging results in preclinical
      studies using xenografted tumor bearing mice and present a whole new avenue for
      radioimmunotherapy and diagnosis of cancer.

PMID- 11578979
TI  - Anti-mucin monoclonal antibodies.
AB  - Mucins are of major interest in cell biology, not only are they highly over
      expressed in many adenocarcinomas (up to 40-fold increase), but also have
      important physiological function, and probably more to be determined (1-3). There
      is much information available on mucins - doubtless because of their unusual
      structure being heavily glycosylated, but also containing a repeat region rich in
      the amino acids serine, threonine and proline. This repeat region confers high
      immunogenicity of the mucins, and as a result, many antibodies (Abs) have been
      made to mucins of different species (4). Furthermore, the production of Abs led
      to the cloning of the cDNAs and armed with these reagents (antibodies, cDNA and
      genomic structures), advances in the knowledge of the structure and function of
      mucins has been rapid, together with the development of transgenic and gene
      knockout animals for biological studies (1-9). Here we describe monoclonal
      antibodies (Mabs) made to the different mucins, including Mucins 1-4,
      concentrating on human Mucin 1 (MUC1), to variants of MUC1, to regions outside
      the VNTR of MUC1, mouse Mucin1 (muc1), unusual features and cross reactions of
      anti-MUC1 Mabs and Abs made by patients in clinical trials. We will especially
      describe the Mabs produced in our laboratory.

PMID- 11578980
TI  - Progress in the battle with the black dog: advances in the treatment of
      depression.

PMID- 11578981
TI  - Neurobiological mechanisms of social anxiety disorder.
AB  - OBJECTIVE: The authors critically surveyed several preclinical and clinical
      neurobiological models of social anxiety disorder. METHOD: The authors reviewed
      the recent literature regarding three animal models of particular relevance to
      social anxiety. They then examined the recent literature concerning clinical
      neurobiological aspects of social anxiety disorder, including the developmental
      neurobiology of anxiety, the genetics of fear and social anxiety, and challenge
      and imaging studies. RESULTS: The available animal models are useful paradigms
      for understanding the features of social subordination stress, attachment
      behavior, and environmental rearing, but they incompletely account for the known
      neurobiology of human social anxiety disorder. The clinical neurobiology
      literature surveyed implicates specific neurotransmitter system abnormalities,
      most notably of the dopamine system, but largely ignores neurodevelopmental
      processes and the functional interactions between neurotransmitters. Both
      heritable factors and environmental stress factors appear to be responsible for
      the onset of social anxiety disorder. CONCLUSIONS: Social anxiety disorder should
      be conceptualized as a chronic neurodevelopmental illness that might represent a
      fully compensated state in adulthood. Future investigations from this perspective
      are discussed.

PMID- 11578982
TI  - A review and meta-analysis of the genetic epidemiology of anxiety disorders.
AB  - OBJECTIVE: The authors conducted meta-analyses of data from family and twin
      studies of panic disorder, generalized anxiety disorder, phobias, and obsessive
      compulsive disorder (OCD) to explore the roles of genetic and environmental
      factors in their etiology. METHOD: MEDLINE searches were performed to identify
      potential primary studies of these disorders. Data from studies that met
      inclusion criteria were incorporated into meta-analyses that estimated summary
      statistics of aggregate familial risk and heritability for each disorder.
      RESULTS: For family studies, odds ratios predicting association of illness in
      first-degree relatives with affection status of the proband (disorder present or
      absent) were homogeneous across studies for all disorders. The calculated summary
      odds ratios ranged from 4 to 6, depending on the disorder. Only for panic
      disorder and generalized anxiety disorder could the authors identify more than
      one large-scale twin study for meta-analysis. These yielded heritabilities of
      0.43 for panic disorder and 0.32 for generalized anxiety disorder. For panic
      disorder, the remaining variance in liability could be attributed primarily to
      nonshared environment. For generalized anxiety disorder, this was true for men,
      but for women, a potentially significant role for common familial environment was
      also seen. CONCLUSIONS: Panic disorder, generalized anxiety disorder, phobias,
      and OCD all have significant familial aggregation. For panic disorder,
      generalized anxiety disorder, and probably phobias, genes largely explain this
      familial aggregation; the role of family environment in generalized anxiety
      disorder is uncertain. The role of nonshared environmental experience is
      significant, underscoring the importance of identifying putative environmental
      risk factors that predispose individuals to anxiety.

PMID- 11578983
TI  - Improving the psychiatric knowledge, skills, and attitudes of primary care
      physicians, 1950-2000: a review.
AB  - OBJECTIVE: The authors reviewed the literature on mental health education for
      primary care physicians and made recommendations for the design of educational
      programs and research. METHOD: They searched the MEDLINE and PsycLIT databases
      from 1950 to 2000 by using a variety of key words and subjects. RESULTS: More
      than 400 articles were identified, ranging from empirical studies to
      philosophical articles. Many identified a perceptual gap between primary care and
      psychiatry as the basis for problems of contextual relevance in psychiatric
      education for primary care practitioners. There were few empirical studies; most
      reported only results of satisfaction surveys or simple tests of knowledge. Long
      term outcomes were less positive; there were important negative findings.
      CONCLUSIONS: An extensive literature published over five decades identified a
      strong need for ongoing mental health training for primary care physicians.
      Helpful recommendations exist related to objectives, methods, and evaluation.
      However, there are organizational and attitudinal issues that may be equally or
      more important for educators to consider than the selection of educational
      methods.

PMID- 11578984
TI  - The human genome: genetic testing and animal models.

PMID- 11578986
TI  - Hypersexual disorder and preoccupation with internet pornography.

PMID- 11578988
TI  - Bridging the millennia: mind meets brain.

PMID- 11578991
TI  - A neuropsychological investigation of prefrontal cortex involvement in acute
      mania.
AB  - OBJECTIVE: Mania has received little attention from a contemporary
      neuropsychological perspective despite its clear resemblance to the disinhibition
      syndrome sometimes seen after frontal brain injury, particularly injury to the
      inferior aspect of the prefrontal cortex. The purpose of this investigation was
      to describe the neuropsychological profile of severe acute mania by using a range
      of tasks selected primarily for the detection of localized neural disruption
      within the prefrontal cortex. METHOD: Fifteen acutely manic inpatients were
      compared with 30 nonpsychiatric subjects on tasks from the Cambridge Automated
      Neuropsychological Test Battery (Tower of London, spatial working memory,
      intradimensional-extradimensional attentional shift, and rapid visual information
      processing tasks) and on the Iowa Gambling Task, Stroop Color and Word Test, a
      verbal fluency task, and the California Verbal Learning Test. RESULTS:
      Discriminant function analysis identified deficits in sustained attention (on the
      rapid visual information processing task) and verbal learning (on the California
      Verbal Learning Test) as the best indicators of manic performance, rather than
      deficits on any of the tests of executive functioning. The model correctly
      classified 91% of subjects overall and 87% of manic subjects. Manic patients did
      not resemble patients with ventromedial prefrontal cortex damage in their
      performance on the Iowa Gambling Task. CONCLUSIONS: Acute mania is characterized
      by core deficits in verbal memory and sustained attention against a background of
      milder impairments in functions that are traditional measures of prefrontal
      cortex integrity (attentional set shifting, planning, working memory). The data
      do not implicate ventral prefrontal cortex disruption as a locus of pathology in
      acute mania. Verbal memory and sustained attention deficits may relate
      differentially to the state and trait characteristics of bipolar disorder.

PMID- 11578992
TI  - Cortisol activity and cognitive changes in psychotic major depression.
AB  - OBJECTIVE: The theory that psychotic major depression is a distinct syndrome is
      supported by reports of statistically significant differences between psychotic
      and nonpsychotic major depression in presenting features, biological measures,
      familial transmission, course and outcome, and response to treatment. This study
      examined differences in performance on a verbal memory test and in cortisol
      levels between patients with psychotic and nonpsychotic major depression and
      healthy volunteers. METHOD: Ten patients with psychotic major depression, 17
      patients with nonpsychotic major depression, and 10 healthy volunteers were
      administered the Wallach Memory Recognition Test and had blood drawn at half-hour
      intervals over the course of an afternoon to assay cortisol levels. RESULTS:
      Subjects with psychotic major depression had a higher rate of errors of
      commission on the verbal memory test (incorrectly identified distracters as
      targets) than did subjects with nonpsychotic major depression or healthy
      volunteers; errors of omission were similar among the three groups. Subjects with
      psychotic major depression had higher cortisol levels throughout the afternoon
      than subjects with nonpsychotic major depression or healthy volunteers. This
      effect became even more pronounced later in the afternoon. CONCLUSIONS: Psychotic
      major depression is endocrinologically different from nonpsychotic major
      depression and produces cognitive changes distinct from those seen in
      nonpsychotic major depression.

PMID- 11578993
TI  - Does thyroid supplementation accelerate tricyclic antidepressant response? A
      review and meta-analysis of the literature.
AB  - OBJECTIVE: The delayed onset of therapeutic response to antidepressants remains a
      major problem in the treatment of depression. Among the strategies to accelerate
      response to treatment, the early addition of thyroid hormone to antidepressants
      has been suggested as a viable method. The authors performed a meta-analysis of
      the literature on the use of thyroid hormone supplementation to accelerate the
      treatment of depression to determine whether there is sufficient evidence to
      support the clinical efficacy of this strategy. METHOD: Both a computer-aided
      search of the National Library of Medicine MEDLINE and an intensive search by
      hand were conducted to identify all double-blind, placebo-controlled studies
      assessing the concomitant administration of thyroid hormone and antidepressant to
      accelerate clinical response in patients with nonrefractory depression. RESULTS:
      Six studies were identified. All were conducted with triiodothyronine (T(3)) and
      a tricyclic antidepressant. Five of the six studies found T(3) to be
      significantly more effective than placebo in accelerating clinical response. The
      pooled, weighted effect size index was 0.58, and the average effect was highly
      significant. Further, the effects of T(3) acceleration were greater as the
      percentage of women participating in the study increased. CONCLUSIONS: This meta
      analysis supports the efficacy of T(3) in accelerating clinical response to
      tricyclic antidepressants in patients with nonrefractory depression. Furthermore,
      women may be more likely than men to benefit from this intervention.

PMID- 11578994
TI  - Treatment of erectile dysfunction in men with depressive symptoms: results of a
      placebo-controlled trial with sildenafil citrate.
AB  - OBJECTIVE: Depressed men commonly have erectile dysfunction, and men with
      erectile dysfunction are frequently depressed. Since the etiologic and modulatory
      relationships between depression and erectile dysfunction have been poorly
      characterized, a 12-week, randomized, double-blind, placebo-controlled trial was
      conducted at 20 urologic clinics to evaluate the effects of sildenafil treatment
      in men with erectile dysfunction and mild-to-moderate comorbid depressive
      illness. METHOD: Men (N=152, mean age=56 years) with erectile dysfunction for >
      or =6 months (mean=5.7 years), a DSM-IV diagnosis of depressive disorder not
      otherwise specified, and a Hamilton Depression Rating Scale score > or =12 (mean
      at baseline=16.9) were randomly assigned to flexible-dose treatment with
      sildenafil citrate or matching placebo. Interviewer-rated and self-report
      instruments were used to assess changes in sexual function, depressive symptoms,
      and quality of life. Conservative criteria were used to classify erectile
      dysfunction treatment response and nonresponse. RESULTS: Sildenafil was strongly
      associated with erectile dysfunction treatment response. Fifty-eight men met the
      conservative criteria for response (48 given sildenafil, 10 given placebo), and
      78 men did not respond (18 given sildenafil, 60 given placebo). Mean decreases of
      10.6 and 2.3 in Hamilton depression scale scores were seen in treatment
      responders and nonresponders, respectively; 76% of treatment responders showed a
      > or =50% decline in Hamilton depression scale score versus 14% of nonresponders.
      Quality of life was similarly improved in treatment responders. CONCLUSIONS:
      Sildenafil is efficacious for erectile dysfunction in men with mild-to-moderate
      depressive illness. Improvement of erectile dysfunction is associated with marked
      improvement in depressive symptoms and quality of life.

PMID- 11578995
TI  - Maternal sertraline treatment and serotonin transport in breast-feeding mother
      infant pairs.
AB  - OBJECTIVE: Pharmacological treatment of postpartum depression is frequently
      complicated by the mother's desire to breast-feed. Although breast milk levels of
      several selective serotonin reuptake inhibitors (SSRIs) have been reported to be
      relatively low, a critical question is whether SSRI exposure during nursing
      results in clinically significant blockade of serotonin (5-HT) reuptake in
      infants. This study determined the degree of transporter blockade in infants
      exposed to sertraline through maternal breast milk. METHOD: The extent of
      maternal and infant transporter blockade was assessed by measurement of platelet
      levels of 5-HT in 14 breast-feeding mother-infant pairs before and after 6-16
      weeks of maternal treatment with sertraline for major depression with postpartum
      onset. Plasma sertraline and desmethylsertraline levels were obtained in 13 of
      these mothers and 11 of their infants. RESULTS: Marked declines in platelet 5-HT
      levels of 70%-96% were observed in mothers after sertraline treatment, 25-200
      mg/day. In contrast, infants showed little or no change in platelet 5-HT levels
      after exposure through breast-feeding. Mean levels of maternal plasma sertraline
      and its major metabolite, desmethylsertraline, were 30.7 ng/ml and 45.3 ng/ml,
      respectively. Drug and drug metabolite concentrations in the infants were at or
      below the lower limit of quantitation. CONCLUSIONS: The data indicate that while
      mothers receiving clinical doses of sertraline experience substantial blockade of
      the platelet 5-HT transporter, platelet 5-HT uptake in nursing infants of treated
      mothers is unaltered. The observations suggest that mothers taking sertraline can
      breast-feed without appreciably affecting peripheral or central 5-HT transport in
      their infants.

PMID- 11578996
TI  - Cost-effectiveness of a collaborative care program for primary care patients with
      persistent depression.
AB  - OBJECTIVE: The authors evaluated the incremental cost-effectiveness of stepped
      collaborative care for patients with persistent depressive symptoms after usual
      primary care management. METHOD: Primary care patients initiating antidepressant
      treatment completed a standardized telephone assessment 6-8 weeks after the
      initial prescription. Those with persistent major depression or significant
      subthreshold depressive symptoms were randomly assigned to continued usual care
      or collaborative care. The collaborative care included systematic patient
      education, an initial visit with a consulting psychiatrist, 2-4 months of shared
      care by the psychiatrist and primary care physician, and monitoring of follow-up
      visits and adherence to medication regimen. Clinical outcomes were assessed
      through blinded telephone assessments at 1, 3, and 6 months. Health services
      utilization and costs were assessed through health plan claims and accounting
      data. RESULTS: Patients receiving collaborative care experienced a mean of 16.7
      additional depression-free days over 6 months. The mean incremental cost of
      depression treatment in this program was $357. The additional cost was
      attributable to greater expenditures for antidepressant prescriptions and
      outpatient visits. No offsetting decrease in use of other health services was
      observed. The incremental cost-effectiveness was $21.44 per depression-free day.
      CONCLUSIONS: A stepped collaborative care program for depressed primary care
      patients led to substantial increases in treatment effectiveness and moderate
      increases in costs. These findings are consistent with those of other randomized
      trials. Improving outcomes of depression treatment in primary care requires
      investment of additional resources, but the return on this investment is
      comparable to that of many other widely accepted medical interventions.

PMID- 11578997
TI  - Residual symptoms and impairment in major depression in the community.
AB  - OBJECTIVE: Studies of patients with major depression in treatment settings have
      found significant residual symptoms and impairment after resolution of the
      depressive episode. However, only a small proportion of individuals with major
      depression seek treatment, and little is known about the residual symptoms and
      impairment associated with major depression in the community. This study used
      data from the National Comorbidity Survey, which included a nationally
      representative household sample of respondents in the United States, to assess
      the course of residual symptoms and impairment after resolution of major
      depressive episodes in the community. METHOD: National Comorbidity Survey
      respondents with lifetime major depression who were currently experiencing a
      major depressive episode and respondents whose last episode had ended more than 1
      to 6 months, more than 6 to 12 months, or more than 12 months ago were compared
      with those without a history of major depression with regard to depressive
      symptoms and days of impairment in work functioning or other activities in the
      past 30 days. RESULTS: Respondents whose last episode of major depression had
      resolved even more than a year ago were still more symptomatic than those without
      a history of major depression, whereas the number of days of impairment returned
      to a level indistinguishable from that of respondents without a history of major
      depression after >6 to 12 months of resolution of the last episode. CONCLUSIONS:
      Major depression in the community, as in treatment settings, is associated with
      residual symptoms and impairment. In the community, however, residual impairment
      may resolve more quickly than residual symptoms.

PMID- 11578998
TI  - Ethnic and sex differences in suicide rates relative to major depression in the
      United States.
AB  - OBJECTIVE: Suicide rates differ between ethnic groups in the United States. Since
      suicide is commonly associated with a mood disorder, the authors compared suicide
      rates relative to depression rates in five ethnic groups in the United States.
      METHOD: Rates of major depression were generated from the Epidemiologic Catchment
      Area study and the Hispanic Health and Nutrition Epidemiologic Survey.
      Sociodemographic effects were determined by examining depression rates for
      respondents who were separated or divorced, earning low incomes, or not working
      for pay. The survey data were analyzed with age and sex standardization to
      generate 1-year prevalence rates of major depression. The depression rates of the
      different ethnic groups were compared and were examined in relation to suicide
      rates. RESULTS: The 1-year prevalence rates of major depression were 3.6% for
      whites, 3.5% for blacks, 2.8% for Mexican Americans, 2.5% for Cuban Americans,
      and 6.9% for Puerto Ricans. Compared to the rate for whites, the rate of
      depression was significantly higher in Puerto Ricans and significantly lower in
      Mexican Americans. Relative to the depression rates, the annual suicide rates
      were higher for males than for females. Mexican American and Puerto Rican males
      had lower relative suicide rates than white males. CONCLUSIONS: Identifying
      reasons for differences in suicide rates relative to depression among ethnic
      groups and between males and females may suggest interventions to reduce suicide
      rates. Some possibilities are that depression differs in form or severity or that
      unidentified factors protect against suicide in different subgroups.

PMID- 11578999
TI  - Neuroanatomy of Down's syndrome: a high-resolution MRI study.
AB  - OBJECTIVE: Down's syndrome, the most common genetic cause of mental retardation,
      results in characteristic physical and neuropsychological findings, including
      mental retardation and deficits in language and memory. This study was undertaken
      to confirm previously reported abnormalities of regional brain volumes in Down's
      syndrome by using high-resolution magnetic resonance imaging (MRI), determine
      whether these volumetric abnormalities are present from childhood, and consider
      the relationship between neuroanatomic abnormalities and the cognitive profile of
      Down's syndrome. METHOD: Sixteen children and young adults with Down's syndrome
      (age range=5-23 years) were matched for age and gender with 15 normal comparison
      subjects. High-resolution MRI scans were quantitatively analyzed for measures of
      overall and regional brain volumes and by tissue composition. RESULTS: Consistent
      with prior imaging studies, subjects with Down's syndrome had smaller overall
      brain volumes, with disproportionately smaller cerebellar volumes and relatively
      larger subcortical gray matter volumes. Also noted was relative preservation of
      parietal lobe gray and temporal lobe white matter in subjects with Down's
      syndrome versus comparison subjects. No abnormalities in pattern of brain
      asymmetry were noted in Down's syndrome subjects. CONCLUSIONS: The results
      largely confirm findings of previous studies with respect to overall patterns of
      brain volumes in Down's syndrome and also provide new evidence for abnormal
      volumes of specific regional tissue components. The presence of these
      abnormalities from an early age suggests that fetal or early postnatal
      developmental differences may underlie the observed pattern of neuroanatomic
      abnormalities and contribute to the specific cognitive and developmental deficits
      seen in individuals with Down's syndrome.

PMID- 11579000
TI  - Separating attention deficit hyperactivity disorder and learning disabilities in
      girls: a familial risk analysis.
AB  - OBJECTIVE: Familial risk analysis was used to clarify the relationship in girls
      between attention deficit hyperactivity disorder (ADHD) and learning disabilities
      in either mathematics or reading. METHOD: The authors assessed the presence of
      ADHD and learning disabilities in 679 first-degree relatives of three groups of
      index children: girls with ADHD and a comorbid learning disability, girls with
      ADHD but no learning disabilities, and a comparison group of girls without ADHD.
      RESULTS: The risk for ADHD was similarly higher in families of ADHD probands with
      and without learning disabilities; both groups had significantly higher rates of
      ADHD than did families of the comparison girls. In contrast, only among relatives
      of ADHD probands with a learning disability was there a higher risk for learning
      disabilities. A strong (although statistically nonsignificant) difference emerged
      that suggested at least some degree of cosegregation of ADHD and learning
      disabilities in family members. There was no evidence of nonrandom mating between
      spouses with ADHD and learning disabilities. CONCLUSIONS: These results extend
      previously reported findings regarding the relationship of ADHD and learning
      disabilities to female subjects and raise the possibility that, in girls, the
      relationship between ADHD and learning disabilities is due to shared familial
      risk factors.

PMID- 11579001
TI  - Further evidence of association between behavioral inhibition and social anxiety
      in children.
AB  - OBJECTIVE: The authors sought to examine psychopathological correlates of
      behavioral inhibition in young offspring of parents with panic disorder and/or
      major depression. METHOD: Behavioral inhibition, determined by using standard
      laboratory observations, was assessed in four groups of children (age 2-6 years):
      129 children of parents with both panic disorder and major depression, 22
      children of parents with panic disorder alone, 49 children of parents with major
      depression alone, and 84 comparison children of parents with neither panic
      disorder nor major depression. Psychopathology in children > or =5 years was
      compared between children with behavioral inhibition (N=64) and without (N=152).
      RESULTS: Social anxiety disorder (social phobia or avoidant disorder) was
      significantly more likely to be found in the children with behavioral inhibition
      (17%) than in those without (5%). Noninhibited children were significantly more
      likely than inhibited children to have disruptive behavior disorders (20% versus
      6%, respectively) and had higher scores on the attention problems scale of the
      Child Behavior Checklist (mean=52.1 versus 50.8). CONCLUSIONS: This study adds to
      the growing literature suggesting an association between behavioral inhibition
      and social anxiety disorder and an inverse relationship between inhibition and
      disruptive behavior disorders.

PMID- 11579002
TI  - Changes in regional cerebral blood flow elicited by craving memories in abstinent
      opiate-dependent subjects.
AB  - OBJECTIVE: The brain circuitry of opiate craving was investigated with positron
      emission tomography (PET) imaging of regional cerebral blood flow (rCBF). METHOD:
      Twelve abstinent opiate-dependent subjects listened to audiotaped
      autobiographical scripts of an episode of craving and a neutral episode while
      undergoing a PET scan with the tracer [(15)O]H(2)O. Statistical parametric
      mapping was used to analyze the PET images of rCBF changes. RESULTS: Comparison
      of the drug-related and neutral stimulus conditions revealed activation of rCBF
      in the left medial prefrontal and left anterior cingulate cortices and
      deactivation in the occipital cortex in response to the drug-related stimulus. A
      further statistical parametric mapping analysis with a subjective rating of
      craving as a covariate showed a positive association of between craving and rCBF
      in the left orbitofrontal cortex. CONCLUSIONS: The patterns of cerebral
      activation reflect the different brain regions mediating the salience of opiate
      related stimuli and the subjective experience of craving for opiates.

PMID- 11579003
TI  - Electrophysiological evidence of serotonergic impairment in long-term MDMA
      ("ecstasy") users.
AB  - OBJECTIVE: "Ecstasy," or 3,4-methylenedioxymethamphetamine (MDMA), causes long
      term impairment to the serotonin (5-HT) system in rats, dogs, and nonhuman
      primates. 5-HT dysfunction has also been observed in human recreational users of
      the drug, but whether 5-HT dysfunction in humans is caused by MDMA has not been
      established, since dysfunction may have preceded MDMA exposure. This ambiguity
      about causation is particularly important in MDMA research, because 5-HT
      deficiency is a predictor of risky behavior. METHOD: The 5-HT function of 22 long
      term MDMA users was compared to that of 20 drug-naive comparison subjects and 19
      cannabis users. 5-HT function was assessed with the intensity dependence
      paradigm, a tool that measures 5-HT-related attenuation of neural response to
      auditory stimuli (measured with EEG). RESULTS: Long-term MDMA users exhibited 5
      HT dysfunction, relative to both cannabis users and drug-naive comparison
      subjects. This dysfunction was related to total MDMA consumption (after removing
      the effect of frequency of use) but not to frequency of use (after removing the
      effect of total consumption). CONCLUSIONS: These data show that 5-HT dysfunction
      occurs in MDMA users, is related to users' MDMA consumption, and is independent
      of cannabis use. The results do not suggest that self-medication explains this
      relationship, because the deficit was related to total MDMA consumption but not
      frequency of consumption. The results are thus consistent with the thesis that
      MDMA consumption causes 5-HT impairment in humans.

PMID- 11579004
TI  - Risk of heavy drinking and alcohol use disorders in social phobia: a prospective
      analysis.
AB  - OBJECTIVE: The risks of heavy drinking and alcohol abuse/dependence were
      prospectively assessed among individuals with DSM-III social phobia and
      individuals with subclinical social phobia (irrational fear of social situations
      without significant impairment or avoidance). METHOD: The baseline interview for
      the Baltimore site of the Epidemiologic Catchment Area program was completed in
      1981. Between 1993 and 1996 the original cohort was traced. Among the 1,161
      individuals who did not have episodes of heavy drinking or current or prior
      alcohol abuse/dependence at baseline, logistic regression was used to assess the
      association of social phobia and subclinical social phobia with incident alcohol
      abuse/dependence and incident episodic heavy drinking. RESULTS: Among the 33
      individuals with a DSM-III diagnosis of social phobia at baseline, only one
      developed heavy drinking by follow-up, and none developed alcohol abuse or
      dependence. Among the 84 individuals with a history of subclinical social phobia,
      the cumulative incidence rates of heavy drinking and alcohol abuse/dependence
      were 119 per 1,000 and 95 per 1,000, respectively. After adjustment for sex, age,
      race, education level, marital status, age at first alcohol intoxication, and
      history of other psychiatric or illicit drug use disorder, the estimated relative
      risk for heavy drinking among respondents with subclinical social phobia was
      2.41, and the estimated relative risk for alcohol abuse/dependence was 2.30,
      relative to respondents without social phobia or subclinical social fears.
      CONCLUSIONS: The data may improve our understanding of the relationship of social
      phobia and risk for alcohol conditions, which may have important implications for
      preventive measures.

PMID- 11579005
TI  - Violence, alcohol, and completed suicide: a case-control study.
AB  - OBJECTIVE: Violent behavior may represent a risk factor for suicide. The authors
      tested the hypothesis that violent behavior in the last year of life is
      associated with completed suicide, even after controlling for alcohol use
      disorders. METHOD: The authors analyzed data from the 1993 National Mortality
      Followback Survey, a nationally representative survey conducted by telephone
      interview with decedents' next of kin. Data on 753 victims of suicide were
      compared with data on 2,115 accident victims. Decedents ranged in age from 20 to
      64. Dichotomous measures of violent behavior in the past year and history of
      alcohol misuse were derived by using the four-item CAGE questionnaire. Multiple
      logistic regression was used to evaluate the interactions of violent behavior
      with alcohol misuse, gender, and age, respectively, in predicting suicide versus
      accidental death. Education and race were included as covariates. RESULTS:
      Violent behavior in the last year of life was a significant predictor of suicide;
      the relationship was especially strong in individuals with no history of alcohol
      misuse, those who were younger, and women. CONCLUSIONS: Violent behavior
      distinguished suicide victims from accident victims, and this finding is not
      attributable to alcohol use disorders alone. Given that violent behavior
      increases the risk of suicide, violence prevention initiatives may serve to
      decrease the risk of suicide as well.

PMID- 11579006
TI  - Randomized controlled trial of motivational interviewing, cognitive behavior
      therapy, and family intervention for patients with comorbid schizophrenia and
      substance use disorders.
AB  - OBJECTIVE: Comorbidity of substance abuse disorders with schizophrenia is
      associated with a greater risk for serious illness complications and poorer
      outcome. Methodologically sound studies investigating treatment approaches for
      patients with these disorders are rare, although recommendations for integrated
      and comprehensive treatment programs abound. This study investigates the relative
      benefit of adding an integrated psychological and psychosocial treatment program
      to routine psychiatric care for patients with schizophrenia and substance use
      disorders. METHOD: The authors conducted a randomized, single-blind controlled
      comparison of routine care with a program of routine care integrated with
      motivational interviewing, cognitive behavior therapy, and family or caregiver
      intervention. RESULTS: The integrated treatment program resulted in significantly
      greater improvement in patients' general functioning than routine care alone at
      the end of treatment and 12 months after the beginning of the study. Other
      benefits of the program included a reduction in positive symptoms and in symptom
      exacerbations and an increase in the percent of days of abstinence from drugs or
      alcohol over the 12-month period from baseline to follow-up. CONCLUSIONS: These
      findings demonstrate the effectiveness of a program of routine care integrated
      with motivational interviewing, cognitive behavior therapy, and family
      intervention over routine psychiatric care alone for patients with comorbid
      schizophrenia and alcohol or drug abuse or dependence.

PMID- 11579007
TI  - Association of the TaqI A polymorphism of the dopamine D(2) receptor gene with
      predisposition to neuroleptic malignant syndrome.
AB  - OBJECTIVE: The pathophysiology of neuroleptic malignant syndrome is mainly
      explained by a central hypodopaminergic state. The familial occurrence of
      neuroleptic malignant syndrome suggests the involvement of a genetic mechanism in
      the predisposition to the syndrome. Therefore, the authors examined the
      association between the TaqI A polymorphism of the dopamine D(2) receptor gene
      (DRD(2)), which alters DRD(2) density and function, and the development of
      neuroleptic malignant syndrome. METHOD: The subjects were 15 psychiatric patients
      who had developed neuroleptic malignant syndrome (12 patients with schizophrenia
      and three with major depression) and 138 patients with schizophrenia who had
      never developed neuroleptic malignant syndrome. The TaqI A genotypes, A1 and A2
      alleles, were determined by the polymerase chain reaction method. RESULTS: The
      frequency of the A1 allele was significantly higher in the patients who had
      developed neuroleptic malignant syndrome (56.8%) than in the patients who had not
      (35.1%). The proportion of the A1 carrier was significantly higher in the
      patients with neuroleptic malignant syndrome (14 [93.3%] of 15 patients) than in
      those without the syndrome (79 [57.2%] of 138 patients). CONCLUSIONS: These
      findings suggest that the TaqI A DRD(2) polymorphism is associated with the
      predisposition to neuroleptic malignant syndrome.

PMID- 11579008
TI  - Magnetic resonance imaging study of the cavum septi pellucidi in patients with
      schizophrenia.
AB  - OBJECTIVE: High-resolution magnetic resonance imaging was used to evaluate the
      prevalence of the cavum septi pellucidi (CSP) in 79 normal subjects and 86
      patients with schizophrenia. METHOD: The CSP was assessed by counting the number
      of consecutive coronal 1-mm slices containing the CSP. A CSP equal to or greater
      than 6 mm in length was defined as large. RESULTS: The CSP was found in 74.4% of
      the patients and 74.7% of the normal subjects, a nonsignificant difference. No
      difference between groups was found in the prevalence of a large CSP.
      CONCLUSIONS: The findings support the idea that a small CSP is a normal
      anatomical variant. More cases of a large CSP are needed to elucidate the
      implications of this abnormality in schizophrenia.

PMID- 11579009
TI  - Association of olanzapine-induced weight gain with an increase in body fat.
AB  - OBJECTIVE: The goal of this study was to explore the pathophysiology of weight
      gain during treatment with olanzapine for schizophrenia. METHOD: The authors used
      a prospective, controlled, open study comparing body weight, body mass index, and
      related biological measures in mentally and physically healthy volunteers and
      olanzapine-treated patients with schizophrenia. Weight, eating behavior, leptin
      serum levels, body mass index, and body composition were assessed over an 8-week
      observation period. RESULTS: A significant increase in body weight, leptin serum
      levels, and percentage of body fat was seen in patients treated with olanzapine,
      but the drug-free comparison group did not show any significant changes. The
      weight gain during antipsychotic treatment with olanzapine was mainly
      attributable to an increase in body fat; patients' lean body mass did not change.
      CONCLUSIONS: In addition to the original finding that an increase in body fat is
      mainly responsible for olanzapine-induced weight gain, these findings confirm
      results obtained in other studies showing increases in body weight and serum
      leptin levels during treatment with second-generation antipsychotics.

PMID- 11579010
TI  - Enhancement of cognitive performance in schizophrenia by addition of tandospirone
      to neuroleptic treatment.
AB  - OBJECTIVE: The goal of this study was to evaluate the effects of the addition of
      tandospirone, a serotonin-1A (5-HT(1A)) agonist, to ongoing treatment with
      typical antipsychotic drugs, on two cognitive domains that are relevant to
      functional outcome in patients with schizophrenia. METHOD: Twenty-six patients
      with schizophrenia who were receiving stable doses of typical antipsychotics were
      randomly assigned to adjunctive treatment with 30 mg/day of tandospirone or
      placebo for 6 weeks. Executive function and verbal memory as well as
      psychopathology were assessed at baseline and after 6 weeks. RESULTS: Both
      cognitive measures improved significantly in the patients who received
      tandospirone; subjects who did not receive tandospirone showed no change. There
      was no significant change in psychopathology ratings in either group.
      CONCLUSIONS: The results suggest the usefulness of 5-HT(1A) agonists for
      enhancing some types of cognitive performance and possibly social and work
      function in patients with schizophrenia.

PMID- 11579011
TI  - Pindolol potentiation of paroxetine for generalized social phobia: a double
      blind, placebo-controlled, crossover study.
AB  - OBJECTIVE: The effectiveness of pindolol as an adjunctive treatment to boost
      response to selective serotonin reuptake inhibitors (SSRIs) in patients with
      generalized social phobia was tested. METHOD: A double-blind, placebo-controlled,
      crossover design was used to compare addition of 5 mg of pindolol t.i.d. or
      placebo for 4 weeks to a steady paroxetine dose. Subjects were 14 patients with
      generalized social phobia who were less than "very much improved" on the Clinical
      Global Impression scale after at least 10 weeks of treatment with a maximally
      tolerated dose of paroxetine. Changes on the Liebowitz Social Anxiety Scale and
      the Social Phobia Inventory scores were compared across the two crossover
      periods. RESULTS: Pindolol was not significantly superior to placebo for
      augmenting the effects of paroxetine on social anxiety symptoms. None of the 14
      subjects was deemed a responder to the pindolol arm of the crossover.
      CONCLUSIONS: Pindolol was no more effective than placebo in augmenting the
      effects of SSRI treatment for generalized social phobia.

PMID- 11579012
TI  - Pregnancy outcome following gestational exposure to venlafaxine: a multicenter
      prospective controlled study.
AB  - OBJECTIVE: Because there are no studies available on the safety of venlafaxine
      during pregnancy, the authors' goal in this study was to determine whether
      venlafaxine increases the risk for major malformations. METHOD: Data on 150 women
      exposed to venlafaxine during pregnancy in seven pregnancy counseling centers
      were compared with data from studies of pregnant women who 1) received selective
      serotonin reuptake inhibitor antidepressants (SSRIs) (N=150) and 2) who received
      nonteratogenic drugs (N=150). RESULTS: Among the 150 women who were exposed to
      venlafaxine during pregnancy, 125 had live births, 18 had spontaneous abortions,
      and seven had therapeutic abortions; two of the babies had major malformations.
      There were no significant differences between these women and the two comparison
      groups on any of the measures analyzed. CONCLUSIONS: These results suggest that
      the use of venlafaxine during pregnancy does not increase the rates of major
      malformations above the baseline rate of 1%-3%.

PMID- 11579014
TI  - Psychiatric comorbidity in pathological gamblers seeking treatment.
AB  - OBJECTIVE: The authors' goal was to determine the frequency of psychiatric
      comorbidity among treatment-seeking pathological gamblers, compare the severity
      of gambling and psychological problems in gamblers with and without comorbid
      disorders, and investigate differences between gamblers with and without comorbid
      disorders in the dopamine D(2) receptor gene (DRD(2)). METHOD: Sixty-nine
      pathological gamblers who consecutively applied to a specialized outpatient
      treatment program were evaluated with structured interviews, self-report
      questionnaires, and psychological scales and were genotyped for a DRD(2)
      polymorphism. RESULTS: A comorbid psychiatric disorder was present in 43 (62.3%)
      of the gamblers. The most frequent diagnoses were personality disorders (N=29
      [42.0%]), alcohol abuse or dependence (N=23 [33.3%]), and adjustment disorders
      (N=12 [17.4%]). Gamblers with comorbid psychiatric disorders had gambling scores
      and psychological scale scores indicating greater severity of gambling and
      psychopathology. Significant differences in DRD(2) allele distribution were found
      in gamblers with and without comorbid disorders. CONCLUSIONS: Psychiatric
      comorbidity is common among pathological gamblers and is associated with greater
      severity of clinical problems. The DRD(2) gene could be a liability genetic
      factor for psychiatric comorbidity in pathological gambling.

PMID- 11579013
TI  - Lack of association between parental alcohol or drug addiction and behavioral
      inhibition in children.
AB  - OBJECTIVE: "Behavioral inhibition to the unfamiliar" has been proposed as a
      precursor to anxiety. A recent study proposed that it may also be a precursor to
      alcoholism. The authors sought to replicate the latter finding through a
      secondary analysis of data from a large study of young children (age 2-6 years)
      offspring of parents with panic and depressive disorders-who had been assessed
      for behavioral inhibition through laboratory-based observations. METHOD: The
      offspring were stratified on the basis of presence or absence of parental
      lifetime history of DSM-III-R alcohol dependence (N=115 versus N=166,
      respectively) or drug dependence (N=78 versus N=203). The rates of behavioral
      inhibition were then compared between groups. RESULTS: Despite adequate power to
      detect associations, neither parental alcohol dependence nor drug dependence was
      associated with a higher risk for behavioral inhibition in the offspring.
      CONCLUSIONS: These results are not consistent with the hypothesis linking
      behavioral inhibition to addictions.

PMID- 11579015
TI  - Agranulocytosis and neutropenia with typical and atypical neuroleptics.

PMID- 11579016
TI  - Topiramate-induced depression.

PMID- 11579017
TI  - Addition of olanzapine for treatment-resistant depression.

PMID- 11579018
TI  - Quetiapine-related tardive dyskinesia.

PMID- 11579019
TI  - Complaints of impaired memory in veterans with PTSD.

PMID- 11579020
TI  - Estrogen-replacement therapy for depression.

PMID- 11579021
TI  - Fluvoxamine for postpartum depression.

PMID- 11579022
TI  - Gene expression in schizophrenia.

PMID- 11579023
TI  - Long-term lithium for bipolar disorder.

PMID- 11579024
TI  - Lithium discontinuation during pregnancy.

PMID- 11579026
TI  - End-of-life questions.

PMID- 11579028
TI  - Bipolar disorder questionnaire.

PMID- 11579031
TI  - Use of psychiatric records.

PMID- 11579032
TI  - Use of alternative medicine.

PMID- 11579052
TI  - What's in a name?

PMID- 11579053
TI  - Warm up. A whiff of the future.

PMID- 11579054
TI  - Headache in sport.

PMID- 11579055
TI  - The medicolegal aspects of automatism in mild head injury.

PMID- 11579056
TI  - Performance in motor sports.

PMID- 11579057
TI  - What is the most appropriate treatment for patellar tendinopathy?

PMID- 11579058
TI  - The last "oxygenless" ascent of Mt. Everest.

PMID- 11579059
TI  - Computerised cognitive assessment of athletes with sports related head injury.
AB  - Professional and amateur participants in many sports are at risk of brain injury
      caused by impact with other players or objects. In many cases, mild cognitive
      deficits may persist after the common neurological signs of brain injury have
      passed. In recent years, the athlete's cognitive status after concussion has been
      measured with conventional "paper and pencil" neuropsychological tests. However,
      such tests are not ideal for sporting settings, as they are designed for the
      detection of gross cognitive impairments at a single assessment, not for the
      identification of mild cognitive deficits on repeated assessment. A number of
      computerised cognitive assessment tests and test batteries have been developed
      over the past two decades. These batteries offer major scientific and practical
      advantages over conventional neuropsychological tests which make them ideal for
      the assessment of cognitive function in sportspeople. This review first describes
      the problems associated with cognitive assessment of people with sports related
      cognitive deficits, and then critically examines the utility of conventional
      neuropsychological and computerised cognitive tests in sporting settings.

PMID- 11579062
TI  - Injury and injury rates in Muay Thai kick boxing.
AB  - OBJECTIVE: To determine the type and number of injuries that occur during the
      training and practice of Muay Thai kick boxing and to compare the data obtained
      with those from previous studies of karate and taekwondo. METHODS: One to one
      interviews using a standard questionnaire on injuries incurred during training
      and practice of Muay Thai kick boxing were conducted at various gyms and
      competitions in the United Kingdom and a Muay Thai gala in Holland. RESULTS: A
      total of 152 people were questioned, 132 men and 20 women. There were 19
      beginners, 82 amateurs, and 51 professionals. Injuries to the lower extremities
      were the most common in all groups. Head injuries were the second most common in
      professionals and amateurs. Trunk injuries were the next most common in
      beginners. The difference in injury distribution among the three groups was
      significant (p< or =0.01). Soft tissue trauma was the most common type of injury
      in the three groups. Fractures were the second most common in professionals, and
      in amateurs and beginners it was sprains and strains (p< or =0.05). Annual injury
      rates were: beginners, 13.5/1000 participants; amateurs, 2.43/1000 participants;
      professionals, 2.79/1000 participants. For beginners, 7% of injuries resulted in
      seven or more days off training; for amateurs and professionals, these values
      were 4% and 5.8% respectively. CONCLUSIONS: The results are similar to those
      found for karate and taekwondo with regard to injury distribution, type, and
      rate. The percentage of injuries resulting in time off training is less.

PMID- 11579061
TI  - Effects of an endurance cycling competition on resting serum insulin-like growth
      factor I (IGF-I) and its binding proteins IGFBP-1 and IGFBP-3.
AB  - OBJECTIVES: To determine whether consecutive bouts of intense endurance exercise
      over a three week period alters serum concentrations of insulin-like growth
      factor I (IGF-I) and/or its binding proteins. METHODS: Seventeen professional
      cyclists (mean (SEM) VO(2)MAX, 74.7 (2.1) ml/kg/min; age, 27 (1) years) competing
      in a three week tour race were selected as subjects. Blood samples were collected
      at each of the following time points: t(0) (control, before the start of
      competition), t(1) (end of first week), and t(3) (end of third week). Serum
      levels of both total and free IGF-I and IGF binding proteins 1 and 3 (IGFBP-1 and
      IGFBP-3) were measured in each of the samples. Cortisol levels were measured in
      nine subjects. RESULTS: A significant (p<0.01) increase was found in total IGF-I
      and IGFBP-1 at both t(1) and t(3) compared with t(o) (IGF-I: 110.9 (17.7), 186.8
      (12.0), 196.9 (14.7) ng/ml at t(0), t(1), and t(3) respectively; IGFBP-1: 54.6
      (6.6), 80.6 (8.0), and 89.2 (7.9) ng/ml at t(0), t(1), and t(3) respectively). A
      significant (p<0.01) decrease was noted in free IGF-I at t(3) compared with both
      t(o) and t(1) (t(0): 0.9 (0.1) ng/ml; t(1): 0.9 (0.1) ng/ml; t(3): 0.7 (0.1)
      ng/ml); in contrast, IGFBP-3 levels remained stable throughout the race.
      CONCLUSIONS: It would appear that the increase in circulating levels of both IGF
      I and its binding protein IGFBP-1 is a short term (one week) endocrine adaptation
      to endurance exercise. After three weeks of training, total IGF-I and IGFBP-1
      remained stable, whereas free IGF-I fell below starting levels.

PMID- 11579064
TI  - Organisation of safety measures in an Alpine World Junior Championship.
AB  - OBJECTIVES: To study the implementation of skiing safety during the Alpine World
      Junior Championship of 1995. METHODS: A map of the area was made with
      descriptions of the slopes and all its facilities and the security measures along
      the course. The number of competitors who started and any injuries reported were
      recorded in a questionnaire. RESULTS: A total of 452 girls and 546 boys started
      in the different races. Only four injuries were recorded, all in girls. The
      overall injury rate was 4 per 1000 runs. An injury rate of 8.3 per 1000 runs was
      recorded in the downhill. One skier had a possibly severe injury (ISS = 14) in
      the downhill; the rest of the injuries were minor (ISS = 1). The mean ISS was 4.3
      and the total ISS was 17. CONCLUSIONS: A significantly higher injury rate was
      recorded for young female than young male racers. The injury rate was
      significantly higher in downhill than the other alpine disciplines in the Alpine
      World Junior Championship. The injury rate was not significantly different from
      that recorded one year previously for Olympic racers, and juniors therefore need
      the same safety measures as Olympic racers.

PMID- 11579063
TI  - Symptoms of musculoskeletal disorders in stage rally drivers and co-drivers.
AB  - BACKGROUND: During stage rallying, musculoskeletal injuries may be provoked by
      the high magnitude of vibration and shock to which the driver and co-driver are
      exposed. Drivers and co-drivers experience similar exposure to whole body
      mechanical shocks and vibration but different exposure to hand/wrist stressors.
      OBJECTIVES: To investigate by a questionnaire study the prevalence of symptoms of
      musculoskeletal injuries after rallying in 13 professional and 105 amateur stage
      rally competitors. METHODS: The self administered questionnaire investigated
      whole body and hand/wrist symptoms of musculoskeletal injury. It was loosely
      based on the Nordic design. RESULTS: 91% of participants who competed or tested
      for more than 10 days a year (n=90) reported discomfort in at least one body area
      after rallying. Problems in the lumbar spine (70%), cervical spine (54%),
      shoulders (47%), and thoracic spine (36%) were the most common. There was a
      higher prevalence of cervical spine discomfort for co-drivers (62%) than for
      drivers (46%). Conversely, there was higher prevalence of discomfort in the hands
      and wrists for drivers (32%) than co-drivers (9%). The prevalence of low back
      pain in rally participants is higher than that generally reported for workers
      exposed to whole body vibration. The prevalence of discomfort in the hand and
      wrist for rally drivers is similar to that previously reported for Formula 1
      drivers. CONCLUSIONS: Most stage rally drivers and co-drivers report symptoms of
      musculoskeletal injury. It is logical to relate the high prevalence of symptoms
      of injury to the extreme environment of the rally car.

PMID- 11579065
TI  - Skateboarding injuries of today.
AB  - BACKGROUND: Skateboarding injuries have increased with the rise in popularity of
      the sport, and the injury pattern can be expected to have changed with the
      development of both skateboard tricks and the materials used for skateboard
      construction. OBJECTIVE: To describe the injury pattern of today. METHODS: The
      pattern of injuries, circumstances, and severity were investigated in a study of
      all 139 people injured in skateboarding accidents during the period 1995-1998
      inclusive and admitted to the University Hospital of Umea. This is the only
      hospital in the area, serving a population of 135 000. RESULTS: Three of the 139
      injured were pedestrians hit by a skateboard rider; the rest were riders. The age
      range was 7-47 years (mean 16). The severity of the injuries was minor (AIS 1) to
      moderate (AIS 2); fractures were classified as moderate. The annual number of
      injuries increased during the study period. Fractures were found in 29% of the
      casualties, and four children had concussion. The most common fractures were of
      the ankle and wrist. Older patients had less severe injuries, mainly sprains and
      soft tissue injuries. Most children were injured while skateboarding on ramps and
      at arenas; only 12 (9%) were injured while skateboarding on roads. Some 37% of
      the injuries occurred because of a loss of balance, and 26% because of a failed
      trick attempt. Falls caused by surface irregularities resulted in the highest
      proportion of the moderate injuries. CONCLUSIONS: Skateboarding should be
      restricted to supervised skateboard parks, and skateboarders should be required
      to wear protective gear. These measures would reduce the number of skateboarders
      injured in motor vehicle collisions, reduce the personal injuries among
      skateboarders, and reduce the number of pedestrians injured in collisions with
      skateboarders.

PMID- 11579067
TI  - The relative stress on the Achilles tendon during ambulation in an ankle
      immobiliser: implications for rehabilitation after Achilles tendon repair.
AB  - BACKGROUND: After Achilles tendon repair, immediate weightbearing and
      immobilisation closer to neutral plantarflexion are thought to limit atrophy and
      stiffness, but may place deleterious stress on the repair. OBJECTIVES: To
      estimate the relative stress on the Achilles tendon during weightbearing with
      immobilisation in varying degrees of plantarflexion. METHODS: Electromyographic
      (EMG) activity from the plantarflexors was recorded during walking in 10 subjects
      (six men, four women) without ankle pathology. Four walking conditions were
      examined: (a) normal walking; (b) immobilised (cam-walker) in neutral
      plantarflexion; (c) immobilised with a 0.5 inch heel lift; (d) immobilised with a
      1 inch heel lift. EMG activity relative to plantarflexor torque was determined
      for each subject during isometric contractions at 25%, 50%, 75%, and 100% of
      maximal voluntary contraction (MVC). EMG activity during walking was calculated
      as a percentage of MVC based on the EMG-torque relation during graded isometric
      contractions. RESULTS: During normal walking, the plantarflexor torque was
      estimated to be 30 (12)% (mean (SD)) of MVC, compared with 21 (15)% MVC for
      immobilisation in neutral (p<0.05), 17 (15)% MVC with the addition of a 0.5 inch
      heel lift (p<0.01), and 12 (12)% MVC with the addition of a 1 inch heel lift
      (p<0.01). The 1 inch heel lift resulted in less than 10 degrees plantarflexion in
      all subjects. CONCLUSIONS: When the ankle is immobilised, stress on the Achilles
      tendon is determined by the degree of plantarflexion and the contractile activity
      of the plantarflexors. In the immobilised ankle, the addition of a 1 inch heel
      lift was sufficient to minimise plantarflexor activity during walking.

PMID- 11579069
TI  - The VISA-A questionnaire: a valid and reliable index of the clinical severity of
      Achilles tendinopathy.
AB  - BACKGROUND: There is no disease specific, reliable, and valid clinical measure of
      Achilles tendinopathy. OBJECTIVE: To develop and test a questionnaire based
      instrument that would serve as an index of severity of Achilles tendinopathy.
      METHODS: Item generation, item reduction, item scaling, and pretesting were used
      to develop a questionnaire to assess the severity of Achilles tendinopathy. The
      final version consisted of eight questions that measured the domains of pain,
      function in daily living, and sporting activity. Results range from 0 to 100,
      where 100 represents the perfect score. Its validity and reliability were then
      tested in a population of non-surgical patients with Achilles tendinopathy (n =
      45), presurgical patients with Achilles tendinopathy (n = 14), and two normal
      control populations (total n = 87). RESULTS: The VISA-A questionnaire had good
      test-retest (r = 0.93), intrarater (three tests, r = 0.90), and interrater (r =
      0.90) reliability as well as good stability when compared one week apart (r =
      0.81). The mean (95% confidence interval) VISA-A score in the non-surgical
      patients was 64 (59-69), in presurgical patients 44 (28-60), and in control
      subjects it exceeded 96 (94-99). Thus the VISA-A score was higher in non-surgical
      than presurgical patients (p = 0.02) and higher in control subjects than in both
      patient populations (p<0.001). CONCLUSIONS: The VISA-A questionnaire is reliable
      and displayed construct validity when means were compared in patients with a
      range of severity of Achilles tendinopathy and control subjects. The continuous
      numerical result of the VISA-A questionnaire has the potential to provide utility
      in both the clinical setting and research. The test is not designed to be
      diagnostic. Further studies are needed to determine whether the VISA-A score
      predicts prognosis.

PMID- 11579070
TI  - Phenylethylamine, a possible link to the antidepressant effects of exercise?
AB  - OBJECTIVES: To determine in this pilot study whether aerobic exercise affects
      phenylacetic acid concentration in the urine. METHODS: Twenty healthy men
      provided 24 hour urine samples on two consecutive days for the determination of
      phenylacetic acid levels. Before and during day 1, subjects refrained from
      physical activity; on day 2 subjects ran on a treadmill at 70% of their maximal
      heart rate reserve (MHRR) for 30 minutes. RESULTS: The 24 hour mean urinary
      concentration of phenylacetic acid was increased by 77% after exercise.
      CONCLUSION: As phenylacetic acid concentration in urine reflects phenylethylamine
      level, which is known to have antidepressant effects, phenylethylamine may be
      linked to the therapeutic effects of physical exercise on depression.

PMID- 11579071
TI  - Provocation by eucapnic voluntary hyperpnoea to identify exercise induced
      bronchoconstriction.
AB  - The International Olympic Committee Medical Commission (IOC-MC) requires
      notification for use of a beta(2) agonist at the Winter Olympic Games in Salt
      Lake City. This notification will be required seven days before the event and
      must be accompanied by objective evidence that justifies the need to use one. The
      IOC-MC has expressed the viewpoint that, at present, eucapnic voluntary
      hyperpnoea (EVH) is the optimal laboratory challenge to confirm that an athlete
      has exercise induced bronchoconstriction (EIB). The EVH test recommended was
      specifically designed to identify EIB. EVH has been performed in thousands of
      subjects in both the laboratory and the field. The test requires the subject to
      hyperventilate dry air containing 5% carbon dioxide at room temperature for six
      minutes at a target ventilation of 30 times the subject's forced expiratory
      volume in one second (FEV(1)). The test conditions can be modified to simulate
      the conditions that give the athlete their symptoms with exercise. A reduction in
      FEV(1) of 10% or more of the value before the test is considered positive.

PMID- 11579072
TI  - Results of a 10 week community based strength and balance training programme to
      reduce fall risk factors: a randomised controlled trial in 65-75 year old women
      with osteoporosis.
AB  - OBJECTIVE: To test the efficacy of a community based 10 week exercise
      intervention to reduce fall risk factors in women with osteoporosis. METHODS:
      Static balance was measured by computerised dynamic posturography (Equitest),
      dynamic balance by timed figure of eight run, and knee extension strength by
      dynamometry. Subjects were randomised to exercise intervention (twice weekly
      Osteofit classes for 10 weeks) or control groups. RESULTS: The outcome in 79
      participants (39 exercise, 40 control) who were available for measurement 10
      weeks after baseline measurement is reported. After confounding factors had been
      controlled for, the exercise group did not make significant gains compared with
      their control counterparts, although there were consistent trends toward greater
      improvement in all three primary outcome measures. Relative to the change in
      control subjects, the exercise group improved by 2.3% in static balance, 1.9% in
      dynamic balance, and 13.9% in knee extension strength. CONCLUSIONS: A 10 week
      community based physical activity intervention did not significantly reduce fall
      risk factors in women with osteoporosis. However, trends toward improvement in
      key independent risk factors for falling suggest that a study with greater power
      may show that these variables can be improved to a level that reaches statistical
      significance.

PMID- 11579073
TI  - Hypothermia during sports swimming in water below 11 degrees C.
AB  - OBJECTIVES: To assess precautions needed to avoid dangerous hypothermia in
      endurance sports swims in water below 11 degrees C, using rectal temperature,
      anthropometric measurements, and voluntary swim times during a six day marathon
      relay swim. METHODS: The time in the water and the decrease in rectal temperature
      were measured during the longest of three to five relay swims by each of eight
      experienced swimmers in 9.4-11.0 degrees C water. Height, weight, and four
      skinfold thicknesses were measured. RESULTS: Swimmers with less subcutaneous fat
      terminated their swims after significantly less time in the water than those with
      thicker skinfold thickness, even though their rectal temperatures were not
      significantly lower. The lowest rectal temperature recorded was 34.3 degrees C.
      CONCLUSIONS: Subjective sensation in these experienced swimmers gave reliable
      guidance on safe durations for swims, and all voluntarily left the water with
      rectal temperatures that present no threat to people able to rewarm in safe
      surroundings. Endurance swims in highly competitive conditions or water below 9
      degrees C may require continuous temperature monitoring for safety.

PMID- 11579074
TI  - Computerised cognitive assessment of concussed Australian Rules footballers.
AB  - BACKGROUND: "Paper and pencil" neuropsychological tests play an important role in
      the management of sports related concussions. They provide objective information
      on the athlete's cognitive function and thus facilitate decisions on safe return
      to sport. It has been proposed that computerised cognitive tests have many
      advantages over such conventional tests, but their role in this domain is yet to
      be established. OBJECTIVES: To measure cognitive impairment after concussion in a
      case series of concussed Australian Rules footballers, using both computerised
      and paper and pencil neuropsychological tests. To investigate the role of
      computerised cognitive tests in the assessment and follow up of sports related
      concussions. METHODS: Baseline measures on the Digit Symbol Substitution Test
      (DSST), Trail Making Test-Part B (TMT), and a simple reaction time (SRT) test
      from a computerised cognitive test battery (CogState) were obtained in 240
      players. Tests were repeated in players who had sustained a concussive injury. A
      group of non-injured players were used as matched controls. RESULTS: Six
      concussions were observed over a period of nine weeks. At the follow up, DSST and
      TMT scores did not significantly differ from baseline scores in both control and
      concussed groups. However, analysis of the SRT data showed an increase in
      response variability and latency after concussion in the injured athletes. This
      was in contrast with a decrease in response variability and no change in latency
      on follow up of the control players (p<0.02). CONCLUSION: Increased variability
      in response time may be an important cognitive deficit after concussion. This has
      implications for consistency of an athlete's performance after injury, as well as
      for tests used in clinical assessment and follow up of head injuries.

PMID- 11579075
TI  - Rupture of the axillary (circumflex) nerve and artery in a champion jockey.
AB  - Rupture of the circumflex artery and nerve, without fracture or dislocation, is a
      rare traumatic event. Such a case is reported in a champion flat jockey who
      sustained blunt trauma to the shoulder after a fall during a race; the literature
      is also reviewed. At urgent surgical exploration, the axillary artery and nerve
      were repaired. The patient subsequently successfully returned to professional
      riding. This case highlights the difficulties in diagnosis and management.

PMID- 11579078
TI  - Fitness leader effectiveness.

PMID- 11579077
TI  - Flexibility versus stretching.

PMID- 11579079
TI  - Sports medicine training in the United States.

PMID- 11579081
TI  - International Symposium on Concussion in Sport. Abstracts.

PMID- 11579082
TI  - Alpha 1-adrenergic modulation of metabotropic glutamate receptor-induced calcium
      oscillations and glutamate release in astrocytes.
AB  - Astrocytic responses to activation of metabotropic glutamate receptors group I
      (mGluRs I) and alpha(1)-adrenoreceptors in cultured cells have been assessed
      using spectral analyzes and calcium imaging. Concentration-dependent changes were
      observed after stimulation with the mGluR I agonist (S)-3,5
      dihydroxyphenylglycine (DHPG). These responses changed from a regular low
      frequency signal with sharp peaks at 1 microm to a pronounced stage of
      irregularity at 10 microm. After stimulation with 100 microm the signal was again
      homogenous in shape and regularity but occurred at a higher frequency. In
      contrast, the spectral properties after stimulation with the alpha(1)
      adrenoreceptor agonist phenylephrine, exhibited considerable variation for all
      investigated concentrations. DHPG-induced increases in [Ca(2+)](i) were also
      associated with astroglial glutamate release, whereas no release was observed
      after noradrenergic stimulation. Both DHPG-mediated calcium signaling and
      glutamate release were inhibited by preincubation with 10 or 100 microm
      phenylephrine. Collectively, the present investigation provides new information
      about the spatial-temporal characteristics of astroglial intracellular calcium
      responses and demonstrates distinct differences between noradrenergic and
      glutamatergic receptors regarding intracellular calcium signaling and coupling to
      glutamate release. The noradrenergic modulation of DHPG-induced responses
      indicates that intracellular astroglial processes can be regulated in a bi
      directional feedback loop between closely connected astrocytes and neurons in the
      central nervous system.

PMID- 11579083
TI  - The microtubule cytoskeleton participates in control of beta2 integrin avidity.
AB  - Leukocyte avidity is regulated by cytoskeletal constraints, which keep beta(2)
      integrins in an inactive mode. Releasing these constraints results in increased
      lateral mobility and clustering of integrins, effectively activating adhesion. At
      least part of the constraint on beta(2) integrins is due to actin; whether other
      cytoskeletal components are involved has not previously been investigated.
      Microtubules are a candidate for control of integrin rearrangement, because they
      modulate focal adhesions, which are sites of interaction between integrins and
      the cytoskeleton. Here we report that both depolymerization of microtubules by
      colchicine or nocodazole and stabilization of microtubules by taxol increased the
      lateral mobility of beta(2) integrins, activating adhesion. Increased integrin
      mobility was accompanied by an increase in tyrosine phosphorylation of paxillin,
      a biochemical event associated with activation of beta(2) integrins. Further, C3
      exoenzyme, an inhibitor of Rho, blocked induction of integrin mobility by
      nocodazole, but not by taxol, suggesting that there are multiple microtubule
      dependent pathways to integrin rearrangement, only some of which require Rho
      activity. Taken together, our data suggest that a dynamic microtubule system is
      required to regulate integrin-cytoskeleton interactions. Furthermore, these data
      demonstrate that microtubules participate in control of integrin rearrangement,
      one of the earliest steps in activation of integrin-mediated adhesion.

PMID- 11579084
TI  - A protective role for kidney apolipoprotein E. Regulation of mesangial cell
      proliferation and matrix expansion.
AB  - Mesangial expansion is a key feature in the pathogenesis of numerous renal
      diseases involving the glomerulus. Studies indicate that mutations in
      apolipoprotein E (apoE) might independently contribute to kidney dysfunction.
      Although the role of apoE as an atheroprotective molecule is well established,
      its role in kidney is unclear. In this study, we sought to explore whether apoE
      has a protective function in kidney. Northern blotting and reverse transcriptase
      polymerase chain reaction showed apoE expression in kidney, and mesangial cell is
      a major source of apoE in kidney. In the kidneys of 14-16-month-old apoE-null
      mice, hematoxylin-eosin (HE) staining revealed increased mesangial cell
      proliferation and matrix formation compared with wild type mice or apoB
      overexpressing mice, which have elevated plasma cholesterol and triglycerides.
      These data suggest that lack of apoE, rather than hyperlipidemia, contributes to
      increased mesangial expansion. We isolated mesangial cells from mouse kidney and
      determined the effect of apoE on cell growth. ApoE (E3, 10 microg/ml) completely
      inhibited serum, platelet-derived growth factor (10 ng/ml), as well as low
      density lipoprotein-induced mesangial cell proliferation. Among the three
      isoforms, E3 was found to be most effective in inhibiting mesangial cell
      proliferation. ApoE did not show any cytotoxic effect, and moreover, inhibited
      mesangial cell apoptosis induced by oxidized low density lipoprotein. These data
      suggest that apoE regulates growth as well as survival of mesangial cells. We
      previously showed that apoE induces matrix heparan sulfate proteoglycan (HSPG) in
      vascular cells, which has an antiproliferative effect. Similarly, apoE induced
      the mesangial matrix HSPG. Perlecan is the major HSPG of mesangial matrix and
      subendothelial space, and consistent with this, blockade of perlecan reversed the
      antiproliferative effect of apoE. Immunohistochemistry revealed reduced staining
      of perlecan in kidney from apoE-null mice. Because the loss of anionic HSPG in
      the basement membrane and mesangial matrix is associated with disruption of
      filtration barrier, these data suggest a novel role for kidney apoE in preserving
      the filtration barrier. In summary, apoE has a protective function in kidney as
      an autocrine regulator of mesangial expansion and kidney function.

PMID- 11579085
TI  - The pro-apoptotic function of death-associated protein kinase is controlled by a
      unique inhibitory autophosphorylation-based mechanism.
AB  - Death-associated protein kinase is a calcium/calmodulin serine/threonine kinase,
      which positively mediates programmed cell death in a variety of systems. Here we
      addressed its mode of regulation and identified a mechanism that restrains its
      apoptotic function in growing cells and enables its activation during cell death.
      It involves autophosphorylation of Ser(308) within the calmodulin (CaM)
      regulatory domain, which occurs at basal state, in the absence of Ca(2+)/CaM, and
      is inversely correlated with substrate phosphorylation. This type of
      phosphorylation takes place in growing cells and is strongly reduced upon their
      exposure to the apoptotic stimulus of C(6)-ceramide. The substitution of Ser(308)
      to alanine, which mimics the ceramide-induced dephosphorylation at this site,
      increases Ca(2+)/CaM-independent substrate phosphorylation as well as binding and
      overall sensitivity of the kinase to CaM. At the cellular level, it strongly
      enhances the death-promoting activity of the kinase. Conversely, mutation to
      aspartic acid reduces the binding of the protein to CaM and abrogates almost
      completely the death-promoting function of the protein. These results are
      consistent with a molecular model in which phosphorylation on Ser(308) stabilizes
      a locked conformation of the CaM-regulatory domain within the catalytic cleft and
      simultaneously also interferes with CaM binding. We propose that this unique
      mechanism of auto-inhibition evolved to impose a locking device, which keeps
      death-associated protein kinase silent in healthy cells and ensures its
      activation only in response to apoptotic signals.

PMID- 11579086
TI  - The polyphosphate bodies of Chlamydomonas reinhardtii possess a proton-pumping
      pyrophosphatase and are similar to acidocalcisomes.
AB  - Acidocalcisomes are acidic calcium storage compartments described initially in
      trypanosomatid and apicomplexan parasites. In this work, we describe organelles
      with properties similar to acidocalcisomes in the green alga Chlamydomonas
      reinhardtii. Nigericin and NH(4)Cl released (45)Ca(2+) from preloaded
      permeabilized cells, suggesting the incorporation of a significant amount of this
      cation into an acidic compartment. X-ray microanalysis of the electron-dense
      vacuoles or polyphosphate bodies of C. reinhardtii showed large amounts of
      phosphorus, magnesium, calcium, and zinc. Immunofluorescence microscopy, using
      antisera raised against a peptide sequence of the vacuolar type proton
      pyrophosphatase (H(+)-PPase) of Arabidopsis thaliana which is conserved in the C.
      reinhardtii enzyme, indicated localization in the plasma membrane, in
      intracellular vacuoles, and the contractile vacuole where it colocalized with the
      vacuolar proton ATPase (V-H(+)-ATPase). Purification of the electron-dense
      vacuoles using iodixanol density gradients indicated a preferential localization
      of the H(+)-PPase and the V-H(+)-ATPase activities in addition to high
      concentrations of PP(i) and short and long chain polyphosphate, but lack of
      markers for mitochondria and chloroplasts. In isolated electron-dense vacuoles,
      PP(i)-driven proton translocation was stimulated by potassium ions and inhibited
      by the PP(i) analog aminomethylenediphosphonate. Potassium fluoride,
      imidodiphosphate, N,N'-dicyclohexylcarbodiimide, and N-ethylmaleimide also
      inhibited PP(i) hydrolysis in the isolated organelles in a dose-dependent manner.
      These results indicate that the electron-dense vacuoles of C. reinhardtii are
      very similar to acidocalcisomes with regard to their chemical composition and the
      presence of proton pumps. Polyphosphate was also localized to the contractile
      vacuole by 4',6-diamidino-2-phenylindole staining, suggesting, with the
      immunochemical data, a link between these organelles and the acidocalcisomes.

PMID- 11579087
TI  - GTPases of the Rho subfamily are required for Brucella abortus internalization in
      nonprofessional phagocytes: direct activation of Cdc42.
AB  - Members of the genus Brucella are intracellular alpha-Proteobacteria responsible
      for brucellosis, a chronic disease of humans and animals. Little is known about
      Brucella virulence mechanisms, but the abilities of these bacteria to invade and
      to survive within cells are decisive factors for causing disease. Transmission
      electron and fluorescence microscopy of infected nonprofessional phagocytic HeLa
      cells revealed minor membrane changes accompanied by discrete recruitment of F
      actin at the site of Brucella abortus entry. Cell uptake of B. abortus was
      negatively affected to various degrees by actin, actin-myosin, and microtubule
      chemical inhibitors. Modulators of MAPKs and protein-tyrosine kinases hampered
      Brucella cell internalization. Inactivation of Rho small GTPases using
      clostridial toxins TcdB-10463, TcdB-1470, TcsL-1522, and TcdA significantly
      reduced the uptake of B. abortus by HeLa cells. In contrast, cytotoxic
      necrotizing factor from Escherichia coli, known to activate Rho, Rac, and Cdc42
      small GTPases, increased the internalization of both virulent and non-virulent B.
      abortus. Expression of dominant-positive Rho, Rac, and Cdc42 forms in HeLa cells
      promoted the uptake of B. abortus, whereas expression of dominant-negative forms
      of these GTPases in HeLa cells hampered Brucella uptake. Cdc42 was activated upon
      cell contact by virulent B. abortus, but not by a noninvasive isogenic strain, as
      proven by affinity precipitation of active Rho, Rac, and Cdc42. The polyphasic
      approach used to discern the molecular events leading to Brucella internalization
      provides new alternatives for exploring the complexity of the signals required by
      intracellular pathogens for cell invasion.

PMID- 11579088
TI  - Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and
      is capable of preventing cell-mediated oxidative modification of low density
      lipoprotein.
AB  - The oxidation of apolipoprotein B-containing lipoproteins and cell membrane
      lipids is believed to play an integral role in the development of fatty streak
      lesions, an initial step in atherogenesis. We have previously shown that two
      antioxidant-like enzymes, paraoxonase (PON)-1 and PON3, are high density
      lipoprotein-associated proteins capable of preventing the oxidative modification
      of low density lipoprotein (LDL) (Reddy, S. T., Wadleigh, D. J., Grijalva, V.,
      Ng, C., Hama, S., Gangopadhyay, A., Shih, D. M., Lusis, A. J., Navab, M., and
      Fogelman, A. M. (2001) Arterioscler. Thromb. Vasc. Biol. 21, 542-547). In the
      present study, we demonstrate that PON2 (i) is not associated with high density
      lipoprotein; (ii) has antioxidant properties; and (iii) prevents LDL lipid
      peroxidation, reverses the oxidation of mildly oxidized LDL (MM-LDL), and
      inhibits the ability of MM-LDL to induce monocyte chemotaxis. The PON2 protein
      was overexpressed in HeLa cells using the tetracycline-inducible ("Tet-On")
      system, and its antioxidant capacity was measured in a fluorometric assay. Cells
      that overexpressed PON2 showed significantly less intracellular oxidative stress
      following treatment with hydrogen peroxide or oxidized phospholipid. Moreover,
      cells that overexpressed PON2 were also less effective in oxidizing and modifying
      LDL and, in fact, were able to reverse the effects of preformed MM-LDL. Our
      results suggest that PON2 possesses antioxidant properties similar to those of
      PON1 and PON3. However, in contrast to PON1 and PON3, PON2 may exert its
      antioxidant functions at the cellular level, joining the host of intracellular
      antioxidant enzymes that protect cells from oxidative stress.

PMID- 11579089
TI  - Formation and implications of a ternary complex of profilin, thymosin beta 4, and
      actin.
AB  - Data from affinity chromatography, analytical ultracentrifugation, covalent cross
      linking, and fluorescence anisotropy show that profilin, thymosin beta(4), and
      actin form a ternary complex. In contrast, steady-state assays measuring F-actin
      concentration are insensitive to the formation of such a complex. Experiments
      using a peptide that corresponds to the N terminus of thymosin beta(4) (residues
      6-22) confirm the presence of an extensive binding surface between actin and
      thymosin beta(4), and explain why thymosin beta(4) and profilin can bind
      simultaneously to actin. Surprisingly, despite much lower affinity, the N
      terminal thymosin beta(4) peptide has a very slow dissociation rate constant
      relative to the intact protein, consistent with a catalytic effect of the C
      terminus on conformational change occurring at the N terminus of thymosin
      beta(4). Intracellular concentrations of thymosin beta(4) and profilin may
      greatly exceed the equilibrium dissociation constant of the ternary complex,
      inconsistent with models showing sequential formation of complexes of profilin
      actin or thymosin beta(4)-actin during dynamic remodeling of the actin
      cytoskeleton. The formation of a ternary complex results in a very large
      amplification mechanism by which profilin and thymosin beta(4) can sequester much
      more actin than is possible for either protein acting alone, providing an
      explanation for significant sequestration even if molecular crowding results in a
      very low critical concentration of actin in vivo.

PMID- 11579090
TI  - Ouabain-induced signaling and vascular smooth muscle cell proliferation.
AB  - The hypothesis of this study is that the sodium pump complex acts as an
      intracellular signal-transducing molecule in canine vascular smooth muscle cells
      through its interaction with other membrane and cytoskeletal proteins. We have
      demonstrated that 1 nm ouabain induced transactivation of the epidermal growth
      factor receptor (EGFR), resulting in increased proliferation and
      bromodeoxyuridine (BrdUrd) uptake. Immunoprecipitation and Western blotting
      showed that the EGFR and Src were phosphorylated within 5 min of 10(-9) m ouabain
      stimulation. Both ouabain-induced DNA synthesis (BrdUrd uptake) and MAPK42/44
      phosphorylation were inhibited by the Src inhibitor PP2, the EGFR kinase
      inhibitor AG1478, the tyrosine kinase inhibitor genistein, and the MEK1 inhibitor
      PD98059. Ouabain concentrations higher than 1 nm had little or no stimulating
      effect on proliferation or BrdUrd uptake but did minimally activate ERK1/2. Thus,
      low concentrations of ouabain, which do not inhibit the sodium pump sufficiently
      to perturb the resting cellular ionic milieu, initiate a transactivational
      signaling cascade leading to vascular smooth muscle cell proliferation.

PMID- 11579091
TI  - Thrombin differentiates normal lung fibroblasts to a myofibroblast phenotype via
      the proteolytically activated receptor-1 and a protein kinase C-dependent
      pathway.
AB  - Myofibroblasts are ultrastructurally and metabolically distinctive fibroblasts
      that express smooth muscle (SM)-alpha actin and are associated with various
      fibrotic lesions. The present study was undertaken to investigate the
      myofibroblast phenotype that appears after activation of normal lung fibroblasts
      by thrombin. We demonstrate that thrombin induces smooth muscle-alpha actin
      expression and rapid collagen gel contraction by normal lung fibroblasts via the
      proteolytically activated receptor-1 and independent of transforming growth
      factor-beta pathway. Using antisense oligonucleotides we demonstrate that a
      decreased level of PKCepsilon abolishes SM-alpha actin expression and collagen
      gel contraction induced by thrombin in normal lung fibroblasts. Inhibition of
      PKCepsilon translocation also abolishes thrombin-induced collagen gel
      contraction, SM-alpha actin increase, and its organization by normal lung
      fibroblasts, suggesting that activation of PKCepsilon is required for these
      effects. In normal lung fibroblasts PKCepsilon binds to SM-alpha actin after
      thrombin treatment, but in activated fibroblasts derived from scleroderma lung
      they associate even in untreated cells. This suggests that SM-alpha actin may
      serve as a substrate for PKCepsilon in lung fibroblasts when activated by
      thrombin. We propose that thrombin differentiates normal lung fibroblasts to a
      myofibroblast phenotype via a PKC-dependent pathway. Thrombin-induced
      differentiation of normal lung fibroblasts to a myofibroblast phenotype resembles
      the phenotype observed in scleroderma lung fibroblasts. Therefore, we conclude
      that chronic exposure to thrombin after microvascular injury leads to activation
      of normal lung fibroblasts and to the appearance of a myofibroblast phenotype in
      vivo. Our study provides novel, compelling evidence that thrombin is an important
      mediator of the interstitial lung fibrosis associated with scleroderma.

PMID- 11579092
TI  - Acid sphingomyelinase-deficient macrophages have defective cholesterol
      trafficking and efflux.
AB  - Cholesterol efflux from macrophage foam cells, a key step in reverse cholesterol
      transport, requires trafficking of cholesterol from intracellular sites to the
      plasma membrane. Sphingomyelin is a cholesterol-binding molecule that transiently
      exists with cholesterol in endosomes and lysosomes but is rapidly hydrolyzed by
      lysosomal sphingomyelinase (L-SMase), a product of the acid sphingomyelinase
      (ASM) gene. We therefore hypothesized that sphingomyelin hydrolysis by L-SMase
      enables cholesterol efflux by preventing cholesterol sequestration by
      sphingomyelin. Macrophages from wild-type and ASM knockout mice were incubated
      with [(3)H]cholesteryl ester-labeled acetyl-LDL and then exposed to
      apolipoprotein A-I or high density lipoprotein. In both cases, [(3)H]cholesterol
      efflux was decreased substantially in the ASM knockout macrophages. Similar
      results were shown for ASM knockout macrophages labeled long-term with
      [(3)H]cholesterol added directly to medium, but not for those labeled for a short
      period, suggesting defective efflux from intracellular stores but not from the
      plasma membrane. Cholesterol trafficking to acyl-coenzyme A:cholesterol
      acyltransferase (ACAT) was also defective in ASM knockout macrophages. Using
      filipin to probe cholesterol in macrophages incubated with acetyl-LDL, we found
      there was modest staining in the plasma membrane of wild-type macrophages but
      bright, perinuclear fluorescence in ASM knockout macrophages. Last, when wild
      type macrophages were incubated with excess sphingomyelin to "saturate" L-SMase,
      [(3)H]cholesterol efflux was decreased. Thus, sphingomyelin accumulation due to L
      SMase deficiency leads to defective cholesterol trafficking and efflux, which we
      propose is due to sequestration of cholesterol by sphingomyelin and possibly
      other mechanisms. This model may explain the low plasma high density lipoprotein
      found in ASM-deficient humans and may implicate L-SMase deficiency and/or
      sphingomyelin enrichment of lipoproteins as novel atherosclerosis risk factors.

PMID- 11579093
TI  - RNA export mediated by tap involves NXT1-dependent interactions with the nuclear
      pore complex.
AB  - Nuclear export of ribonucleoprotein complexes requires cis-acting signals and
      recognition by receptors that mediate translocation through the nuclear pore
      complex. Translocation is likely to involve a series of physical interactions
      between the ribonucleoprotein complex and nucleoporins within the nuclear pore
      complex. Here, we have characterized the function of NXT1 in the context of the
      Tap-dependent RNA export pathway. Tap has been implicated in the nuclear export
      of RNA transcripts derived from Mason-Pfizer monkey virus that contain the
      constitutive transport element. We demonstrate that NXT1 stimulates binding of a
      Tap-RNA complex to nucleoporins in vitro, and we provide mutational analysis that
      shows these interactions are necessary for nuclear export of an intron-containing
      viral mRNA in vivo. Tap contains separate domains for binding to nucleoporins and
      NXT1, both of which are critical for its export function. RNA export is mediated
      by a heterodimer of Tap and NXT1, and the function of NXT1 on this pathway is to
      regulate the affinity of the Tap-RNA complex for nucleoporins within the nuclear
      pore complex. We propose that NXT1-dependent binding of the Tap-RNA complex to
      the nucleoporin p62, which we have reconstituted in vitro using recombinant
      proteins, represents a single step of the translocation reaction.

PMID- 11579094
TI  - Doxorubicin-induced apoptosis is associated with increased transcription of
      endothelial nitric-oxide synthase. Effect of antiapoptotic antioxidants and
      calcium.
AB  - The clinical efficacy of the antitumor antibiotic drug doxorubicin (DOX) is
      severely limited by its dose-limiting cardiotoxicity in cancer patients. DOX
      induced generation of reactive oxygen species was proposed to be a major
      mechanism of its cardiotoxicity. Previously, we showed that DOX undergoes a
      reductive activation at the reductase domain of endothelial nitric-oxide synthase
      (eNOS) forming the semiquinone and superoxide (Vasquez-Vivar, J., Martasek, P.,
      Hogg, N., Masters, B. S. S., Pritchard, K. A., Jr., and Kalyanaraman, B. (1997)
      Biochemistry 36, 11293-11297). In this report, we provide evidence for DOX
      induced increase in eNOS transcription and protein expression in bovine aortic
      endothelial cells (BAEC). We propose that DOX-induced hydrogen peroxide formation
      is responsible for the increased transcription of eNOS. BAEC treated with
      antisense eNOS oligonucleotide inhibits DOX-induced endothelial apoptosis.
      Treatment with antioxidants restored the levels of antiapoptotic proteins (Hsp70
      and Bcl-2) in DOX-treated BAEC. DOX-induced intracellular oxidative stress, as
      measured by oxidation of dichlorodihydrofluorescein diacetate to
      dichlorofluorescein and hydroethidium to ethidium, was inhibited by antisense
      eNOS oligonucleotide and antioxidant treatment. Furthermore, antiapoptotic
      antioxidants (e.g. FeTBAP, ebselen, and alpha-phenyl-tert-butyl nitrone)
      inhibited DOX-induced eNOS transcription. We conclude that DOX-induced apoptosis
      is linked to the redox activation of DOX by eNOS.

PMID- 11579095
TI  - The proto-oncoprotein Brx activates estrogen receptor beta by a p38 mitogen
      activated protein kinase pathway.
AB  - The estrogen receptors (ERs) are ligand-inducible transcription factors that play
      key roles in the control of growth and differentiation in reproductive tissues.
      We showed that the novel Dbl family proto-oncoprotein Brx enhances ligand
      dependent activity of ERalpha via a Cdc42-dependent pathway. Brx also
      significantly enhances ligand-dependent activity of ERbeta. This enhancement is
      not affected by inhibition of p44/42 mitogen-activated protein kinase (MAPK)
      activation by PD98059. However, addition of the p38 MAPK inhibitor SB202190
      abrogates the enhancement of ERbeta activity by Brx, showing that p38 MAPK
      activity is required for the enhancement of ERbeta function by Brx. In COS-7
      cells, transfection of Brx leads to activation of endogenous p38 MAPK activity.
      Co-expression of the beta2 isoform of human p38 MAPK and a constitutively active
      form of the p38 MAPK kinase MKK6 (MKK6-EE) synergistically augments ligand
      dependent activity of ERbeta. Our findings suggest that p38 MAPKs may be
      important regulators of ERbeta activity.

PMID- 11579096
TI  - The signal transfer regions of G alpha(s).
AB  - The crystal structure of soluble functional fragments of adenylyl cyclase
      complexed with G alpha(s) and forskolin, shows three regions of G alpha(s) in
      direct contact with adenylyl cyclase. The functions of these three regions are
      not known. We tested synthetic peptides encoding these regions of G alpha(s) on
      the activities of full-length adenylyl cyclases 2 and 6. A peptide encoding the
      Switch II region (amino acids 222-247) stimulated both adenylyl cyclases 2- to 3
      fold. Forskolin synergized the stimulation. Addition of peptides in the presence
      of activated G alpha(s) partially inhibited G alpha(s) stimulation. Corresponding
      Switch II region peptides from G alpha(q) and G alpha(i) did not stimulate
      adenylyl cyclase. A peptide encoding the Switch I region (amino acids 199-216)
      also stimulated AC2 and AC6. The stimulatory effects of the two peptides at
      saturating concentrations were non-additive. A peptide encoding the third contact
      region (amino acids 268-286) located in the alpha 3-beta 5 region, inhibits
      basal, forskolin, and G alpha(s)-stimulated enzymatic activities. Since this
      region in G alpha(s) interacts with both the central cytoplasmic loop and C
      terminal tail of adenylyl cyclases this peptide may be involved in blocking
      interactions between these two domains. These functional data in conjunction with
      the available structural information suggest that G alpha(s) activation of
      adenylyl cyclase is a complex event where the alpha 3-beta 5 loop of G alpha(s)
      may bring together the central cytoplasmic loop and C-terminal tail of adenylyl
      cyclase thus allowing the Switch I and Switch II regions to function as signal
      transfer regions to activate adenylyl cyclase.

PMID- 11579097
TI  - 4.1R proteins associate with interphase microtubules in human T cells: a 4.1R
      constitutive region is involved in tubulin binding.
AB  - Red blood cell protein 4.1 (4.1R) is an 80-kDa protein that stabilizes the
      spectrin-actin network and anchors it to the plasma membrane. To contribute to
      the characterization of functional roles and partners of specific nonerythroid
      4.1R isoforms, we analyzed 4.1R in human T cells and found that endogenous 4.1R
      was distributed to the microtubule network. Transfection experiments of T cell
      4.1R cDNAs in conjunction with confocal microscopy analysis revealed the
      colocalization of exogenous 4.1R isoforms with the tubulin skeleton. Biochemical
      analyses using Taxol (paclitaxel)-polymerized microtubules from stably
      transfected T cells confirmed the association of the exogenous 4.1R proteins with
      microtubules. Consistent with this, endogenous 4.1R immunoreactive proteins were
      also detected in the microtubule-containing fraction. In vitro binding assays
      using glutathione S-transferase-4.1R fusion proteins showed that a constitutive
      domain of the 4.1R molecule, one that is therefore present in all 4.1R isoforms,
      is responsible for the association with tubulin. A 22-amino acid sequence
      comprised in this domain and containing heptad repeats of leucine residues was
      essential for tubulin binding. Furthermore, ectopic expression of 4.1R in COS-7
      cells provoked microtubule disorganization. Our results suggest an involvement of
      4.1R in interphase microtubule architecture and support the hypothesis that some
      4.1R functional activities are cell type-regulated.

PMID- 11579098
TI  - The phosphoinositide-dependent kinase, PDK-1, phosphorylates conventional protein
      kinase C isozymes by a mechanism that is independent of phosphoinositide 3
      kinase.
AB  - Phosphorylation by the phosphoinositide-dependent kinase, PDK-1, is required for
      the activation of diverse members of the AGC family of protein kinases, including
      the protein kinase C (PKC) isozymes. Here we explore the subcellular location of
      the PDK-1-mediated phosphorylation of conventional PKCs, and we address whether
      this phosphorylation is regulated by phosphoinositide 3-kinase. Pulse-chase
      experiments reveal that newly synthesized endogenous PKC alpha is primarily
      phosphorylated in the membrane fraction of COS-7 cells, where it is processed to
      a species that is phosphorylated at the activation loop and at two carboxyl
      terminal positions. This "mature" species is then released into the cytosol.
      Deletion of the plekstrin homology domain of PDK-1 results in a 4-fold increase
      in the rate of processing of PKC indicating an autoinhibitory role for this
      domain. Autoinhibition by the plekstrin homology domain is not relieved by
      binding 3'-phosphoinositides; PKC is phosphorylated at a similar rate in serum
      treated cells and serum-starved cells treated with the phosphoinositide 3-kinase
      inhibitors, LY294002 and wortmannin. Under the same conditions, the PDK-1
      catalyzed phosphorylation of another substrate, Akt/protein kinase B, is
      abolished by these inhibitors. Our data are consistent with a model in which PDK
      1 phosphorylates newly synthesized PKC by a mechanism that is independent of 3'
      phosphoinositides.

PMID- 11579099
TI  - Mitochondrial respiratory chain adjustment to cellular energy demand.
AB  - Because adaptation to physiological changes in cellular energy demand is a
      crucial imperative for life, mitochondrial oxidative phosphorylation is tightly
      controlled by ATP consumption. Nevertheless, the mechanisms permitting such large
      variations in ATP synthesis capacity, as well as the consequence on the overall
      efficiency of oxidative phosphorylation, are not known. By investigating several
      physiological models in vivo in rats (hyper- and hypothyroidism, polyunsaturated
      fatty acid deficiency, and chronic ethanol intoxication) we found that the
      increase in hepatocyte respiration (from 9.8 to 22.7 nmol of O(2)/min/mg dry
      cells) was tightly correlated with total mitochondrial cytochrome content,
      expressed both per mg dry cells or per mg mitochondrial protein. Moreover, this
      increase in total cytochrome content was accompanied by an increase in the
      respective proportion of cytochrome oxidase; while total cytochrome content
      increased 2-fold (from 0.341 +/- 0.021 to 0.821 +/- 0.024 nmol/mg protein),
      cytochrome oxidase increased 10-fold (from 0.020 +/- 0.002 to 0.224 +/- 0.006
      nmol/mg protein). This modification was associated with a decrease in the overall
      efficiency of the respiratory chain. Since cytochrome oxidase is well recognized
      for slippage between redox reactions and proton pumping, we suggest that this
      dramatic increase in cytochrome oxidase is responsible for the decrease in the
      overall efficiency of respiratory chain and, in turn, of ATP synthesis yield,
      linked to the adaptive increase in oxidative phosphorylation capacity.

PMID- 11579100
TI  - Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene
      regulation, and cell transformation.
AB  - Signal transducers and activators of transcription (STATs) comprise a family of
      cytoplasmic signaling proteins that participates in normal cellular responses to
      cytokines and growth factors. Frequently, however, constitutive activation of
      certain STAT family members, particularly Stat3, has accompanied a wide variety
      of human malignancies. To identify small molecule inhibitors of Stat3, we
      investigated the ability of the Stat3 SH2 domain-binding peptide, PY*LKTK (where
      Y* represents phosphotyrosine), to disrupt Stat3 activity in vitro. The presence
      of PY*LKTK, but not PYLKTK or PFLKTK, in nuclear extracts results in significant
      reduction in the levels of DNA binding activities of Stat3, to a lesser extent of
      Stat1, and with no effect on that of Stat5. Analyses of alanine scanning
      mutagenesis and deletion derivatives of PY*LKTK reveal that the Leu residue at
      the Y+1 position and a substituent at the Y-1 position (but not necessarily Pro)
      are essential for the disruption of active Stat3, thereby mapping the minimum
      active sequence to the tripeptide, XY*L. Studies involving bead-coupled PY*LKTK
      peptide demonstrate that this phosphopeptide directly complexes with Stat3
      monomers in vitro, suggesting that PY*LKTK disrupts Stat3:Stat3 dimers. As
      evidence for the functional importance of peptide-directed inhibition of Stat3,
      PY*LKTK-mts (mts, membrane translocating sequence) selectively inhibits
      constitutive and ligand-induced Stat3 activation in vivo. Furthermore, PY*LKTK
      mts suppresses transformation by the Src oncoprotein, which has been shown
      previously to require constitutive Stat3 activation. Altogether, we have
      identified a minimal peptide that inhibits Stat3 signaling and provides the
      conceptual basis for use of this peptide as a lead for novel peptidomimetic drug
      design.

PMID- 11579101
TI  - Photodynamic therapy-induced apoptosis in epidermoid carcinoma cells. Reactive
      oxygen species and mitochondrial inner membrane permeabilization.
AB  - Photodynamic therapy (PDT), a novel and promising cancer treatment that employs a
      combination of a photosensitizing chemical and visible light, induces apoptosis
      in human epidermoid carcinoma A431 cells. However, the precise mechanism of PDT
      induced apoptosis is not well characterized. To dissect the pathways of PDT
      induced apoptosis, we investigated the involvement of mitochondrial damage by
      examining a second generation photosensitizer, the silicon phthalocyanine 4 (Pc
      4). By using laser-scanning confocal microscopy, we found that Pc 4 localized to
      cytosolic membranes primarily, but not exclusively, in mitochondria. Formation of
      mitochondrial reactive oxygen species (ROS) was detected within minutes when
      cells were exposed to Pc 4 and 670-675 nm light. This was followed by
      mitochondrial inner membrane permeabilization, depolarization and swelling,
      cytochrome c release, and apoptotic death. Desferrioxamine prevented
      mitochondrial ROS production and the events thereafter. Cyclosporin A plus
      trifluoperazine, blockers of the mitochondrial permeability transition, inhibited
      mitochondrial inner membrane permeabilization and depolarization without
      affecting mitochondrial ROS generation. These data indicate that the
      mitochondrial ROS are critical in initiating mitochondrial inner membrane
      permeabilization, which leads to mitochondrial swelling, cytochrome c release to
      the cytosol, and apoptotic death during PDT with Pc 4.

PMID- 11579102
TI  - Mitochondrial processing of newly synthesized steroidogenic acute regulatory
      protein (StAR), but not total StAR, mediates cholesterol transfer to cytochrome
      P450 side chain cleavage enzyme in adrenal cells.
AB  - The metabolism of cholesterol by cytochrome P450 side chain cleavage enzyme is
      hormonally regulated in steroidogenic tissues via intramitochondrial cholesterol
      transport. The mediating steroidogenic acute regulatory protein (StAR) is
      synthesized as a 37-kDa (p37) precursor that is phosphorylated by protein kinase
      A and cleaved within the mitochondria to generate 30-kDa forms (p30, pp30). The
      effectiveness of modified recombinant StAR forms in COS-1 cells without
      mitochondrial import has led to a prevailing view that cholesterol transport is
      mediated by p37 StAR via activity on the outer mitochondrial membrane. The
      present study of the activation of cholesterol metabolism by bromo-cAMP in
      adrenal cells in relation to (35)S-StAR turnover indicates that targeting of pp30
      to the inner membrane provides the dominant cholesterol transport mechanism. We
      show that 1) only newly synthesized StAR is functional, 2) phosphorylation and
      processing of p37 to pp30 occurs rapidly and stoichiometrically, 3) both steps
      are necessary for optimum transport, and 4) newly synthesized pp30 exhibits very
      high activity (400 molecules of cholesterol/StAR/min). Segregation of cAMP
      activation and synthesis of StAR from cholesterol metabolism showed that very low
      levels of newly synthesized StAR (1 fmol/min/10(6) cells) sustained activated
      cholesterol metabolism (0.4 pmol/min/10(6) cells, t(1/2) = 70 min) long after
      complete removal of p37 (t(1/2) = 5 min). This activity was highly sensitive to
      inhibition of processing by CCCP only until sufficient pp30 was formed. Maximum
      activation preceded bromo-cAMP-induced StAR expression, indicating other limiting
      steps in cholesterol metabolism.

PMID- 11579103
TI  - GATA-3 has dual regulatory functions in human interleukin-5 transcription.
AB  - Interleukin-5 (IL-5) is a T-cell cytokine involved in Type 2 diseases and is
      commonly described as being coordinately regulated with other Type 2 cytokines,
      such as IL-4 and IL-13. Considering the unique control of eosinophilia by IL-5,
      such coordinate regulation would be surprising. In fact, the biological
      specificity of eosinophilia and its control by IL-5 suggests a unique and
      independent control of IL-5 regulation. In this report we show the binding of
      GATA-3 to three sites in the human IL-5 promoter in the human T-cell line PER117.
      The previously identified -70 site and another site at position -152 are shown to
      positively regulate IL-5 transcription. More importantly, the site located at 
      400 acts as a powerful repressor of IL-5 transcription with mutagenesis of this
      site allowing a high level expression of IL-5 without the activation of other
      factors normally required for IL-5 expression. Whereas GATA-3 has been proposed
      to be involved in the regulation of the IL-4/IL-5/IL-13 locus, we show here that
      it has another function in controlling IL-5 transcription that supports the
      observed unique biological function of this cytokine.

PMID- 11579104
TI  - Desensitization of the Y1 cell adrenocorticotropin receptor: evidence for a
      restricted heterologous mechanism implying a role for receptor-effector
      complexes.
AB  - Receptor desensitization provides a potential mechanism for the regulation of
      adrenocortical adrenocorticotropin (ACTH) responsiveness. Using the mouse
      adrenocortical Y1 cell line we demonstrate that ACTH effectively desensitizes the
      cAMP response of its own receptor, the melanocortin 2 receptor (MC2R), in these
      cells with a maximal effect between 30 and 60 min. Neither forskolin nor
      isoproterenol (in Y1 cells stably transfected with the beta(2)-adrenergic
      receptor) desensitize this ACTH response. ACTH desensitizes its receptor at
      concentrations at which only a fraction of receptors are occupied, implying that
      this mechanism acts on agonist-unoccupied receptors. Y1 cells express G protein
      coupled receptor kinase (GRK) 2 and 5, but stable expression of a dominant
      negative GRK2 (K220W) only marginally reduces the desensitization by ACTH. The
      protein kinase A (PKA) inhibitor, H89, extinguishes almost the entire
      desensitization response over the initial 30-min period at all concentrations of
      ACTH. A mutant MC2R in which the single consensus PKA phosphorylation site has
      been mutated (S208A) when expressed in MC2R-negative Y6 cells is also unable to
      desensitize. These data imply a heterologous, PKA-dependent, mode of
      desensitization, which is restricted to agonist-occupied and -unoccupied MC2R,
      possibly as a consequence of receptor/effector complexes that functionally
      compartmentalize this receptor.

PMID- 11579105
TI  - Cloning and characterization of a novel mouse Siglec, mSiglec-F: differential
      evolution of the mouse and human (CD33) Siglec-3-related gene clusters.
AB  - A novel mouse Siglec (mSiglec-F) belonging to the subfamily of Siglec-3-related
      Siglecs has been cloned and characterized. Unlike most human Siglec-3 (hSiglec-3)
      related Siglecs with promiscuous linkage specificity, mSiglec-F shows a strong
      preference for alpha2-3-linked sialic acids. It is predominantly expressed in
      immature cells of the myelomonocytic lineage and in a subset of CD11b (Mac-1)
      positive cells in some tissues. As with previously cloned Siglec-3-related
      mSiglecs, the lack of strong sequence similarity to a singular hSiglec made
      identification of the human ortholog difficult. We therefore conducted a
      comprehensive comparison of Siglecs between the human and mouse genomes. The
      mouse genome contains eight Siglec genes, whereas the human genome contains 11
      Siglec genes and a Siglec-like gene. Although a one-to-one orthologous
      correspondence between human and mouse Siglecs 1, 2, and 4 is confirmed, the
      Siglec-3-related Siglecs showed marked differences between human and mouse. We
      found only four Siglec genes and two pseudogenes in the mouse chromosome 7 region
      syntenic to the Siglec-3-related gene cluster on human chromosome 19, which, in
      contrast, contains seven Siglec genes, a Siglec-like gene, and thirteen
      pseudogenes. Although analysis of gene maps and exon structures allows tentative
      assignments of mouse-human Siglec ortholog pairs, the possibility of unequal
      genetic recombination makes the assignments inconclusive. We therefore support a
      temporary lettered nomenclature for additional mouse Siglecs. Current information
      suggests that mSiglec-F is likely a hSiglec-5 ortholog. The previously reported
      mSiglec-3/CD33 and mSiglec-E/MIS are likely orthologs of hSiglec-3 and hSiglec-9,
      respectively. The other Siglec-3-like gene in the cluster (mSiglec-G) is probably
      a hSiglec-10 ortholog. Another mouse gene (mSiglec-H), without an apparent human
      ortholog, lies outside of the cluster. Thus, although some duplications of Siglec
      3-related genes predated separation of the primate and rodent lineages (about 80
      100 million years ago), this gene cluster underwent extensive duplications in the
      primate lineage thereafter.

PMID- 11579106
TI  - A novel sugar-stimulated covalent switch in a sugar sensor.
AB  - The bgl sensory system is composed of a membrane-bound sugar sensor, BglF, and a
      transcriptional regulator, BglG. The sensor BglF has several enzymatic
      activities: in its nonstimulated state, it acts as BglG phosphorylase; in the
      presence of beta-glucoside in the growth medium, it acts as BglG dephosphorylase
      and as the beta-glucoside phosphotransferase. The same active site on BglF, Cys
      24, is responsible for the phosphorylation of both the stimulating sugar and the
      BglG protein. BglF is composed of three domains, two hydrophilic and one
      hydrophobic. Our previous results suggested that catalysis of the sugar
      stimulated functions depends on specific interactions between the B domain, which
      contains the active site cysteine, and the integral membrane C domain. We report
      here that the stimulating sugar triggers the formation of a disulfide bond
      between the active site cysteine and another cysteine in the membrane-embedded
      domain of BglF. Inability of a mutant BglF protein to form the disulfide bridge
      between the B and C domains correlates with its inability to catalyze the sugar
      stimulated functions. The ability of the cysteine residue in BglF to bind
      covalently either to a phosphoryl group or to another cysteine residue, depending
      on the protein stimulation state, suggests a novel way to control signaling by
      alternative bond formation.

PMID- 11579107
TI  - Calmodulin-binding and autoinhibitory domains of Acanthamoeba myosin I heavy
      chain kinase, a p21-activated kinase (PAK).
AB  - The sequence homology between Acanthamoeba myosin I heavy chain kinase (MIHCK)
      and other p21-activated kinases (PAKs) is relatively low, including only the
      catalytic domain and a short PAK N-terminal motif (PAN), and even these regions
      are not highly homologous. In this paper, we report the expression in insect
      cells of full-length, fully regulated Acanthamoeba MIHCK and further characterize
      the regulation of this PAK by Rac, calmodulin, and autoinhibition. We map the
      autoinhibitory region of MIHCK to its PAN region and show that the PAN region
      inhibits autophosphorylation and kinase activity of unphosphorylated full-length
      MIHCK and its expressed catalytic domain but has very little effect on either
      when they are phosphorylated. These properties are similar to those reported for
      mammalian PAK1. Unlike PAK1, MIHCK is activated by Rac only in the presence of
      phospholipid. However, peptides containing the PAN region of MIHCK bind Rac in
      the absence of lipid, and Rac binding reverses the inhibition of the MIHCK
      catalytic domain by PAN peptides. Our data suggest that a region N-terminal to
      PAN is required for optimal binding of Rac. Also unlike mammalian PAK,
      phospholipid stimulation of Acanthamoeba MIHCK and Dictyostelium MIHCK) (which is
      also a PAK) is inhibited by Ca(2+)-calmodulin. In contrast to Dictyostelium
      MIHCK, however, Ca(2+)-calmodulin also inhibits Rac-induced activity of
      Acanthamoeba MIHCK. The basic region N-terminal to PAN is essential for
      calmodulin binding.

PMID- 11579108
TI  - Eukaryotic DNA polymerases: proposal for a revised nomenclature.

PMID- 11579109
TI  - Balancing the possible effectiveness of postoperative radiotherapy for non-small
      cell lung cancer against the possible detriment of radiation-induced toxicity.

PMID- 11579110
TI  - Some like it hot!

PMID- 11579111
TI  - Risk of death from intercurrent disease is not excessively increased by modern
      postoperative radiotherapy for high-risk resected non-small-cell lung carcinoma.
AB  - PURPOSE: Some studies report a high risk of death from intercurrent disease (DID)
      after postoperative radiotherapy (XRT) for non-small-cell lung cancer (NSCLC).
      This study determines the risk of DID after modern-technique postoperative XRT.
      PATIENTS AND METHODS: A total of 202 patients were treated with surgery and
      postoperative XRT for NSCLC. Most patients (97%) had pathologic stage II or III
      disease. Many patients (41%) had positive/close/uncertain resection margins. The
      median XRT dose was 55 Gy with fraction size of 1.8 to 2 Gy. The risk of DID was
      calculated actuarially and included patients who died of unknown/uncertain
      causes. Median follow-up was 24 months for all patients and 62 months for
      survivors. RESULTS: A total of 25 patients (12.5%) died from intercurrent
      disease, 16 from confirmed noncancer causes and nine from unknown causes. The 4
      year actuarial rate of DID was 13.5%. This is minimally increased compared with
      the expected rate for a matched population (approximately 10% at 4 years). On
      multivariate analysis, age and radiotherapy dose were borderline significant
      factors associated with a higher risk of DID (P =.06). The crude risk of DID for
      patients receiving less than 54 Gy was 2% (4-year actuarial risk 0%) versus 17%
      for XRT dose > or = 54 Gy. The 4-year actuarial overall survival was 34%; local
      control was 84%; and freedom from distant metastases was 37%. CONCLUSION: Modern
      postoperative XRT for NSCLC does not excessively increase the risk of
      intercurrent deaths. Further study of postoperative XRT, particularly when using
      more sophisticated treatment planning and reasonable total doses, for carefully
      selected high-risk resected NSCLC is warranted.

PMID- 11579112
TI  - Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade
      or transformed low-grade B-cell non-Hodgkin's lymphomas.
AB  - PURPOSE: To evaluate the efficacy and safety of tositumomab and iodine I 131
      tositumomab (Bexxar; Corixa Corp, Seattle, WA, and GlaxoSmithKline, Philadelphia,
      PA) in patients with chemotherapy-refractory low-grade or transformed low-grade
      non-Hodgkin's lymphoma (NHL) and to compare its efficacy to the patients' last
      qualifying chemotherapy (LQC) regimens. PATIENTS AND METHODS: Sixty patients who
      had been treated with at least two protocol-specified qualifying chemotherapy
      regimens and had not responded or progressed within 6 months after their LQC were
      treated with a single course of iodine I 131 tositumomab. RESULTS: Patients had
      received a median of four prior chemotherapy regimens. A partial or complete
      response (CR) was observed in 39 patients (65%) after iodine I 131 tositumomab,
      compared with 17 patients (28%) after their LQC (P <.001). The median duration of
      response (MDR) was 6.5 months after iodine I 131 tositumomab, compared with 3.4
      months after the LQC (P <.001). Two patients (3%) had a CR after their LQC,
      compared with 12 (20%) after iodine I 131 tositumomab (P <.001). The MDR for CR
      was 6.1 months after the LQC and had not been reached with follow-up of more than
      47 months after iodine I 131 tositumomab. An independent review panel verified
      that 32 (74%) of the 43 patients with nonequivalent durations of response (> 30
      days difference) had a longer duration of response after iodine I 131 tositumomab
      (P <.001). Only one patient was hospitalized for neutropenic fever. Five patients
      (8%) developed human antimurine antibodies, and one (2%) developed an elevated
      TSH level after treatment. Myelodysplasia was diagnosed in four patients in
      follow-up. CONCLUSION: A single course of iodine I 131 tositumomab was
      significantly more efficacious than the LQC received by extensively pretreated
      patients with chemotherapy-refractory, low-grade, or transformed low-grade NHL
      and had an acceptable safety profile.

PMID- 11579113
TI  - Randomized clinical trial of adjuvant fluorouracil, epirubicin, and
      cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative
      breast cancer.
AB  - PURPOSE: The prospective applicability of new biologic tumor information to
      personalize adjuvant treatment of women with operable breast cancer remains to be
      demonstrated. The aim of the present study was to investigate whether patients
      with fast-proliferating, node-negative breast cancer could benefit from adjuvant
      chemotherapy with fluorouracil, epirubicin, and cyclophosphamide (FEC). PATIENTS
      AND METHODS: Beginning in November 1989, we analyzed the proliferative activity
      of primary tumors in a consecutive series of women with node-negative breast
      cancer to identify subgroups of patients with a worse prognosis and who were
      therefore suitable candidates for adjuvant systemic therapy. Proliferative
      activity was determined by means of the [3H]-thymidine incorporation assay using
      an autoradiographic technique. Women with fast-proliferating breast cancer ([3H]
      thymidine labeling index, > 2.3%) were randomized to receive either six cycles of
      adjuvant FEC or no adjuvant therapy until disease progression. RESULTS: One
      hundred twenty-five and 123 patients treated with radical surgery for pT1 to T2,
      N0, M0 breast cancer were randomized to the FEC and control arms, respectively.
      After a median follow-up of 70 months, 27 events (21.6%) were observed in the FEC
      arm and 39 (32.2%) in the control arm, with a significantly lower number of
      locoregional relapses in the FEC group. Five-year disease-free survival (DFS) was
      81% in the FEC group and 69% in the control group (P <.02 by log-rank test). Cox
      multivariate analysis described the impact of adjuvant therapy with FEC on DFS as
      independent of the patients' main clinical-pathologic characteristics.
      CONCLUSION: FEC adjuvant polychemotherapy seems able to significantly improve the
      clinical outcome of patients with fast-proliferating, node-negative breast
      cancer.

PMID- 11579114
TI  - Efficacy of contralateral prophylactic mastectomy in women with a personal and
      family history of breast cancer.
AB  - PURPOSE: To estimate the efficacy of contralateral prophylactic mastectomy in
      women with a personal and family history of breast cancer. PATIENTS AND METHODS:
      We followed the course of 745 women with a first breast cancer and a family
      history of breast and/or ovarian cancer who underwent contralateral prophylactic
      mastectomy at the Mayo Clinic between 1960 and 1993. Family history information
      and cancer follow-up information were obtained from the medical record, a study
      specific questionnaire, and telephone follow-up. Life-tables for contralateral
      breast cancers, which consider age at first breast cancer, current age, and type
      of family history, were used to calculate the number of breast cancers expected
      in our cohort had they not had a prophylactic mastectomy. RESULTS: Of the 745
      women in our cohort, 388 were premenopausal (age < 50 years) and 357 were post-
      menopausal. Eight women developed a contralateral breast cancer. Six events were
      observed among the premenopausal women, compared with 106.2 predicted, resulting
      in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For
      the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted,
      whereas only two were observed, representing a 96.0% risk reduction (95% CI,
      85.6% to 99.5%). CONCLUSION: The incidence of contralateral breast cancer seems
      to be reduced significantly after contralateral prophylactic mastectomy in women
      with a personal and family history of breast cancer.

PMID- 11579115
TI  - Molecular screening for hereditary nonpolyposis colorectal cancer: a prospective,
      population-based study.
AB  - PURPOSE: Germline mutations in mismatch repair genes predispose to hereditary
      nonpolyposis colorectal cancer (HNPCC). To address effective screening programs,
      the true incidence of the disease must be known. Previous clinical investigations
      reported estimates ranging between 0.5% and 13% of all the colorectal cancer
      (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2% to
      2.7% of mutation carriers for the disease. The aim of the present report is to
      establish the frequency of the disease in a high-incidence area for colon cancer.
      PATIENTS AND METHODS: Through the data of the local CRC registry, we
      prospectively collected all cases of CRC from January 1, 1996, through December
      31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9% of the incident
      cases) were screened for microsatellite instability (MSI) with six to 12 mono-
      and dinucleotide markers. MSI cases were subjected to MSH2 and MLH1 germline
      mutation analysis and immunohistochemistry; the methylation of the promoter
      region was studied for MLH1. RESULTS: Twenty-eight cases (8.3% of the total)
      showed MSI. MSI cases differed significantly from microsatellite-stable (MSS)
      cases for their proximal location (P <.01), high mucinous component (P <.01), and
      poor differentiation (P =.002). Of MSI cases studied (n = 12), only one with a
      family history compatible with HNPCC had a germline mutation (in MSH2). Five
      other patients with a family history of HNPCC (two with MSI and three with MSS
      tumors) did not show germline mutations. CONCLUSION: We conclude that the
      incidence of molecularly confirmed HNPCC (one [0.3%] of 336) in a high-incidence
      area for CRC is lower than in previous biomolecular and clinical estimates.

PMID- 11579116
TI  - Ectopic expression of guanylyl cyclase C in CD34+ progenitor cells in peripheral
      blood.
AB  - PURPOSE: To examine the utility of guanylyl cyclase C (GC-C)-specific nested
      reverse transcriptase polymerase chain reaction (RT-PCR) to detect circulating
      tumor cells in patients with colorectal cancer. PATIENTS AND METHODS: Peripheral
      blood mononuclear cells from 24 patients with Dukes' stage D colorectal cancer
      were analyzed by GC-C-specific nested RT-PCR using 1 microg of total RNA.
      Peripheral-blood mononuclear cells from 20 healthy volunteers served as controls.
      Additionally, peripheral-blood CD34+ progenitor cells were assayed for the
      expression of both GC-C and other epithelial cell-specific markers. RESULTS: GC-C
      mRNA was detected in blood mononuclear cells from all 24 patients with colorectal
      cancer and all healthy volunteers. These unexpected positive results reflected
      low-level ectopic transcription of GC-C in CD34+ progenitor cells. Moreover,
      CD34+ progenitor cells expressed other epithelial cell-specific markers,
      including prostate-specific antigen, prostate-specific membrane antigen,
      carcinoembryonic antigen, CK-19, CK-20, mucin 1, and GA733.2. Limiting the
      quantity of mononuclear cell total RNA analyzed to < or = 0.8 microg eliminated
      detection of GC-C and other tissue-specific transcripts in blood of healthy
      volunteers. However, under the same conditions, GC-C mRNA was detected in
      mononuclear cells from all 24 patients with metastatic colorectal cancer. Using
      0.5 microg of total RNA and GC-C-specific primers, nested RT-PCR detected a
      single human colon carcinoma cell (approximately 20 to 200 GC-C transcripts/cell)
      in 10(6) to 10(7) mononuclear blood cells. CONCLUSION: These data suggest that GC
      C may be useful for detecting circulating colorectal cancer cells. They also
      demonstrate that CD34+ cells are a source of ectopically expressed epithelial
      cell-specific markers and that CD34+ cells may contribute to the high false
      positive rate generally observed when those markers are used to detect rare
      circulating metastatic cancer cells by RT-PCR.

PMID- 11579117
TI  - Clinical value of routine serum squamous cell carcinoma antigen in follow-up of
      patients with early-stage cervical cancer.
AB  - PURPOSE: To investigate the contribution to recurrence detection and survival of
      serum squamous cell carcinoma antigen (SCC-ag) analysis in the follow-up of early
      stage cervical cancer patients. PATIENTS AND METHODS: Follow-up data were
      evaluated in patients with early-stage squamous cell cervical cancer treated by
      radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy.
      Routine serum SCC-ag determination was performed at each follow-up visit.
      RESULTS: Recurrent disease occurred in 35 (16%) of 225 patients and was preceded
      or accompanied by serum SCC-ag elevation 26 times (sensitivity, 74%). In five
      (14%) of these 35 patients, elevated serum SCC-ag was the first measured clinical
      indicator. Desite salvage therapy, all five patients died of disease. In the
      other 31 patients (21 with serum SCC-ag elevation), either symptoms and/or
      positive signs led to recurrence detection. Median survival time after recurrence
      was worse (9 months; range, 2 to 112+) for patients with an elevated serum SCC-ag
      value at recurrence in comparison with patients with normal serum SCC-ag values
      (20 months; range, 4 to 96; P <.01). In 23 of the 190 patients without
      recurrences, serum SCC-ag values became falsely elevated. In 16 of these 23
      patients, the repeat sample after 6 weeks showed a normal SCC-ag, and in seven
      patients benign (especially skin) disorders were found. CONCLUSION: Serum SCC-ag
      analysis results in earlier recurrence detection in a small proportion (14%) of
      patients but did not contribute to better survival. As long as treatment
      possibilities for recurrent cervical cancer patients are not improved, serum SCC
      ag analysis should not be carried out in routine follow-up.

PMID- 11579118
TI  - Oral topotecan as single-agent second-line chemotherapy in patients with advanced
      ovarian cancer.
AB  - PURPOSE: To evaluate oral topotecan as single-agent, second-line therapy in
      patients with ovarian cancer previously treated with a platinum-based regimen.
      PATIENTS AND METHODS: Patients (N = 116) received oral topotecan 2.3 mg/m2 daily
      for 5 days every 21 days. Eligibility criteria included histologic diagnosis of
      International Federation of Gynecology and Obstetrics stage III or IV epithelial
      ovarian cancer, bidimensionally measurable disease, prior platinum-containing
      chemotherapy, age > or = 18 years, performance status < or = 2, and life
      expectancy > or = 12 weeks. RESULTS: Overall response rate was 21.6% (25 of 116
      patients). Median duration of response was 25.0 weeks; median time to response
      was 8.4 weeks. Median time to progression was 14.1 weeks; median survival was
      62.2 weeks. Grade 4 neutropenia was experienced by 50.4% of patients in 13.4% of
      courses administered. Grade 4 thrombocytopenia was experienced by 22.1% of
      patients in 5.1% of courses. Grade 3 or 4 anemia was experienced by 29.2% of
      patients in 8.5% of courses. Most frequent nonhematologic toxicities were
      predominantly (> 90%) grade 1 or 2 and included nausea, alopecia, diarrhea, and
      vomiting. CONCLUSION: Second-line oral topotecan administered at 2.3 mg/m2 for 5
      days every 21 days demonstrated activity in patients with progressive or
      recurrent ovarian cancer after first-line platinum-based chemotherapy. This
      activity was comparable to that seen in previous studies with intravenous
      topotecan. Grade 4 neutropenia was less frequent with oral topotecan than
      previously reported for intravenous topotecan. Oral topotecan is an active,
      tolerable, and convenient formulation of an established agent for the second-line
      treatment of advanced epithelial ovarian cancer and may also facilitate exploring
      prolonged treatment schedules.

PMID- 11579119
TI  - Specific targeting, biodistribution, and lack of immunogenicity of chimeric anti
      GD3 monoclonal antibody KM871 in patients with metastatic melanoma: results of a
      phase I trial.
AB  - PURPOSE: KM871 is a chimeric monoclonal antibody against the ganglioside antigen
      GD3, which is highly expressed on melanoma cells. We conducted an open-label,
      dose escalation phase I trial of KM871 in patients with metastatic melanoma.
      PATIENTS AND METHODS: Seventeen patients were entered onto one of five dose
      levels (1, 5, 10, 20, and 40 mg/m2). Patients received three infusions of KM871
      at 2-week intervals, with the first infusion of KM871 trace-labeled with indium
      111 (111In) to enable assessment of biodistribution in vivo. Biopsies of
      metastatic melanoma sites were performed on days 7 to 10. RESULTS: Fifteen of 17
      patients completed a cycle of three infusions of KM871. No dose-limiting toxicity
      was observed during the trial; the maximum-tolerated dose was therefore not
      reached. Three patients (at the 1-, 5-, and 40-mg/m2 dose levels) developed pain
      and/or erythema at tumor sites consistent with an inflammatory response. No
      normal tissue uptake of 111In-KM871 was observed, and tumor uptake of 111In-KM871
      was observed in all lesions greater than 1.5 cm (tumor biopsy 111KM871 uptake
      results: range, 0.001% to 0.026% injected dose/g). The ratio of maximum tumor to
      normal tissue was 15:1. Pharmacokinetic analysis revealed a 111In-KM871 terminal
      half-life of 7.68 +/- 2.94 days. One patient had a clinical partial response that
      lasted 11 months. There was no serologic evidence of human antichimeric antibody
      in any patient, including one patient who received 16 infusions over a 12-month
      period. CONCLUSION: This study is the first to demonstrate the biodistribution
      and specific targeting of an anti-GD3 antibody to metastatic melanoma in
      patients. The long half-life and lack of immunogenicity of KM871 makes this
      antibody an attractive potential therapy for patients with metastatic melanoma.

PMID- 11579120
TI  - Unusual sites of involvement by hematologic malignancies. Case 1. Intravascular
      large B-cell lymphoma presenting with CNS symptoms.

PMID- 11579121
TI  - Unusual sites of involvement by hematologic malignancies. Case 2. Meningeal
      myeloma with cord compression.

PMID- 11579122
TI  - Unusual sites of involvement by hematologic malignancies. Case 3. External
      auditory canal tumor: a rare chloroma in acute promyelocytic leukemia with a
      complete response to arsenic trioxide.

PMID- 11579123
TI  - The power of silence.

PMID- 11579124
TI  - Medical Research Council adjuvant trial in high-grade gliomas.

PMID- 11579125
TI  - Aromatase inhibitors: treatment of advanced breast cancer.

PMID- 11579126
TI  - A "good death" revisited in the context of doctor-patient relationships.

PMID- 11579127
TI  - Prior invasive fungal infection is not a contraindication for subsequent
      allogeneic bone marrow transplantation in adult patients with hematologic
      malignancies.

PMID- 11579128
TI  - Study of the brain serotonergic system with labeled alpha-methyl-L-tryptophan.
AB  - alpha-Methyl-L-tryptophan (alpha-MTrp) is an artificial amino acid and an analog
      of tryptophan (Trp), the precursor of the neurotransmitter serotonin (5-HT). In
      this article we have summarized available data, which suggest that the
      measurement of the unidirectional uptake of alpha-MTrp and its conversion to 5-HT
      synthesis rates is a valid approach for the determination of brain 5-HT synthesis
      rates. The main feature on which the model is based is the trapping of labeled
      alpha-MTrp in brain tissue. An overview of opposing opinions, which suggest that
      there is a need for a metabolic conversion of tracer, is also presented and
      discussed critically. As with all biological modeling there is likely to be room
      for improvements of the proposed biological model. In addition, there are a
      limited number of clearly defined circumstances in which the method is confounded
      by the metabolism of labeled alpha-MTrp via the kynurenine pathway. Nonetheless,
      a significant body of evidence suggests that labeled alpha-MTrp is a useful
      tracer to study brain 5-HT synthesis in most circumstances. Calculation of 5-HT
      synthesis rates depends on the plasma-free tryptophan concentration, which,
      according to the balance of arguments in the literature, is a more appropriate
      parameter than the total-plasma tryptophan. The method, as proposed by us, can be
      used in conjunction with autoradiographic measurements in laboratory animals, and
      with positron emission tomography in large animals and humans. We review studies
      in animals looking at the normal control of 5-HT synthesis and the way in which
      it is altered by drugs, as well as initial studies investigating healthy humans
      and patients with neuropsychiatric disorders.

PMID- 11579129
TI  - Distinct roles of the Y1 and Y2 receptors on neuropeptide Y-induced sensitization
      to sedation.
AB  - Intracranial injection of neuropeptide Y (NPY) increases the sensitivity to
      sodium pentobarbital and ketamin sedation and has similar properties as GABA
      agonists on sleep. Mice sensitive to sedation have increased levels of NPY in
      many brain regions and Y1(-/-) mice show a marked resistance to barbiturates.
      Here we characterized the role of the NPY Y receptors in anesthetic-induced
      sedation. We show that Y1 and Y2, but not Y5, receptors participate in the
      modulation of sedation. Administration of a Y1 agonist increased the sodium
      pentobarbital-induced sedation and Y1(-/-) mice were less sensitive to this
      anesthetic. However, Y2(-/-) mice display increased sensitivity, showing that Y2
      modulates GABAergic induced sedation both pharmacologically and physiologically
      and has a functionally opposing role to the Y1 receptor. Analysis of Y1(-/-)/Y2(
      /-) double mutant mice show that increased sensitivity by Y1 occurs independent
      of the Y2 receptor, while the decreased sensitivity mediated by Y2 depend on an
      intact Y1 receptor. In contrast to sodium pentobarbital, both Y1 and Y2 receptors
      increase the sensitivity in a collaborative fashion to NMDA antagonist-induced
      sedation. These data demonstrate the physiological and pharmacological impact of
      the Y1 and Y2 receptors on sedation.

PMID- 11579130
TI  - Early ethanolamine phospholipid translocation marks stress-induced apoptotic cell
      death in oligodendroglial cells.
AB  - The consequences of H(2)O(2)/Fe(2+)-induced oxidative stress on translocation of
      ethanolamine phosphoglyceride (EPG) and serine phosphoglyceride (SPG) were
      studied in an oligodendroglia-like cell line (OLN 93) following 3 days of
      supplementation with 0.1 mM docosahexaenoic acid (DHA) and a series of polar head
      group precursors, including N-monomethyl- and N,N-dimethylethanolamine at
      millimolar concentrations. Added DHA was predominantly esterified in EPG species
      and those cells enriched in DHA showed enhanced sensitivity to oxidative stress
      and eventually died by apoptosis. Co-supplements with ethanolamine and DHA
      resulted in a rapid, but transient, EPG translocation with a maximum at 30 min
      following stress, as characterized by a trinitrobenzenesulfonic acid reagent.
      There was no significant translocation of SPG as evidenced by annexin V binding.
      Unlike SPG, which is usually irreversibly translocated to subserve as a tag for
      phagocytosis, EPG acted as a signaling molecule with biphasic kinetic
      characteristics. N-Monomethyl- and N,N-dimethylethanolamine supplements reduced
      EPG synthesis, prevented its externalization and rescued cells from apoptotic
      death. Following stress, the fatty acid profile of the externalized EPG showed
      marked losses in polyunsaturated fatty acids and aldehydes compared with the
      remaining intracellular EPG. Prevention of EPG species selective translocation to
      the outer membrane leaflet by altering phospholipid asymmetry may be important in
      the mechanism of rescue from cell death.

PMID- 11579131
TI  - CREB DNA binding activity is inhibited by glycogen synthase kinase-3 beta and
      facilitated by lithium.
AB  - The regulatory influences of glycogen synthase kinase-3 beta (GSK3 beta) and
      lithium on the activity of cyclic AMP response element binding protein (CREB)
      were examined in human neuroblastoma SH-SY5Y cells. Activation of Akt (protein
      kinase B) with serum-increased phospho-serine-9-GSK3 beta (the inactive form of
      the enzyme), inhibited GSK3 beta activity, and increased CREB DNA binding
      activity. Inhibition of GSK3 beta by another paradigm, treatment with the
      selective inhibitor lithium, also increased CREB DNA binding activity. The
      inhibitory regulation of CREB DNA binding activity by GSK3 beta also was evident
      in differentiated SH-SY5Y cells, indicating that this regulatory interaction is
      maintained in non-proliferating cells. These results demonstrate that inhibition
      of GSK3 beta by serine-9 phosphorylation or directly by lithium increases CREB
      activation. Conversely, overexpression of active GSK3 beta to 3.5-fold the normal
      levels completely blocked increases in CREB DNA binding activity induced by
      epidermal growth factor, insulin-like growth factor-1, forskolin, and cyclic AMP.
      The inhibitory effects due to overexpressed GSK3 beta were reversed by treatment
      with lithium and with another GSK 3beta inhibitor, sodium valproate. Overall,
      these results demonstrate that GSK3 beta inhibits, and lithium enhances, CREB
      activation.

PMID- 11579132
TI  - Stress proteins in oligodendrocytes: differential effects of heat shock and
      oxidative stress.
AB  - Heat shock proteins (HSP) or stress proteins serve as biomarkers to identify the
      contribution of stress situations underlying the pathogenesis of degenerative
      diseases of the CNS. We have analyzed by immunoblot technique the constitutive
      and inducible occurrence of stress proteins in cultured rat brain
      oligodendrocytes subjected to heat shock or oxidative stress exerted by hydrogen
      peroxide, or a combination of both. The data demonstrate that oligodendrocytes
      constitutively express HSP32, HSP60 and the cognate form of the HSP70 family of
      proteins, HSC70. After heat shock, HSP25, alpha B-crystallin and HSP70 were up
      regulated, while after oxidative stress the specific induction of HSP32 and alpha
      B-crystallin was observed. HSP32 represents heme oxygenase 1 (HO-1), a small
      stress protein with enzymatic activity involved in the oxidative degradation of
      heme which participates in iron metabolism. The presence of the iron chelators
      phenanthroline or deferoxamine (DFO), which previously has been shown to protect
      oligodendrocytes from oxidative stress-induced onset of apoptosis, caused a
      marked stimulation of HSP32 without affecting HSP70. This indicates that DFO
      possibly exerts its protective role by directly influencing the antioxidant
      capacity of HO-1. In summary, HSP in oligodendrocytes are differentially
      stimulated by heat stress and oxidative stress. Heme oxygenase-1 has been linked
      to inflammatory processes and oxidative stress, its specific up-regulation after
      oxidative stress in oligodendrocytes suggests that it is an ideal candidate to
      investigate the involvement of oxidative stress in demyelinating diseases.

PMID- 11579133
TI  - Ca(2+)-dependent K(+) current and exocytosis in responses to caffeine and
      muscarine in voltage-clamped guinea-pig adrenal chromaffin cells.
AB  - We characterized changes in membrane currents and the cytosolic Ca(2+)
      concentration, [Ca(2+)](i), in response to caffeine, and compared them with those
      in response to muscarine using the perforated patch-clamp technique and fura-2
      microfluorimetry in guinea-pig adrenal chromaffin cells. Catecholamine release
      from single voltage-clamped cells was monitored with amperometry using carbon
      microelectrodes. Caffeine produced a transient outward current (I(out)) at
      holding potentials over - 60 mV, increasing in amplitude with increasing the
      potentials. It also evoked a rapid increase of [Ca(2+)](i) at all potentials
      examined. The current-voltage relation revealed that the activation of K(+)
      channels was responsible for the I(out) evoked by caffeine. Both current and
      [Ca(2+)](i) responses were reversibly abolished by cyclopiazonic acid, an
      inhibitor of Ca(2+)-pump ATPase. At - 30 mV, the caffeine-induced I(out), but not
      [Ca(2+)](i), was partly inhibited by either charybdotoxin or apamin. In the
      majority of cells tested, caffeine induced a larger I(out) but a smaller
      [Ca(2+)](i) increase than muscarine. Caffeine and muscarine increased
      catecholamine release from voltage-clamped single cells concomitant with the
      transient increase of [Ca(2+)](i), and there was a positive correlation between
      them. These results indicate that caffeine activates Ca(2+)-dependent K(+)
      channels and catecholamine secretion due to the release of Ca(2+) from internal
      stores in voltage-clamped adrenal chromaffin cells of the guinea-pig. There seems
      to be a spatial difference between [Ca(2+)](i) increased by Ca(2+) release from
      caffeine-sensitive stores and that released from muscarine (inositol 1,4,5
      trisphosphate)-sensitive ones.

PMID- 11579134
TI  - Ca(2+)-induced inhibition of apoptosis in human SH-SY5Y neuroblastoma cells:
      degradation of apoptotic protease activating factor-1 (APAF-1).
AB  - During apoptotic and excitotoxic neuron death, challenged mitochondria release
      the pro-apoptotic factor cytochrome c. In the cytosol, cytochrome c is capable of
      binding to the apoptotic protease-activating factor-1 (APAF-1). This complex
      activates procaspase-9 in the presence of dATP, resulting in caspase-mediated
      execution of apoptotic neuron death. Many forms of Ca(2+)-mediated neuron death,
      however, do not lead to prominent activation of the caspase cascade despite
      significant release of cytochrome c from mitochondria. We demonstrate that
      elevation of cytosolic Ca(2+) induced prominent degradation of APAF-1 in human SH
      SY5Y neuroblastoma cells and in a neuronal cell-free apoptosis system. Loss of
      APAF-1 correlated with a reduced ability of cytochrome c to activate caspase-3
      like proteases. Ca(2+) induced the activation of calpains, monitored by the
      cleavage of full-length alpha-spectrin into a calpain-specific 150-kDa breakdown
      product. However, pharmacological inhibition of calpain activity indicated that
      APAF-1 degradation also occurred via calpain-independent pathways. Our data
      suggest that Ca(2+) inhibits caspase activation during Ca(2+)-mediated neuron
      death by triggering the degradation of the cytochrome c-binding protein APAF-1.

PMID- 11579135
TI  - Rapid induction and Ca(2+) influx-mediated suppression of vitamin D3 up-regulated
      protein 1 (VDUP1) mRNA in cerebellar granule neurons undergoing apoptosis.
AB  - Cerebellar granule neurons (CGNs) grown under depolarizing conditions with high
      K(+) (HK; 30 mM) undergo apoptosis following replacement of HK by physiological
      K(+) (5.4 mM). Differential display analysis identified eight genes up-regulated
      in this paradigm of apoptosis. Vitamin D3 up-regulated protein 1 (VDUP1) mRNA was
      markedly up-regulated as early as 2 h following HK withdrawal. VDUP1 mRNA was up
      regulated in other paradigms of neuronal apoptosis as well both in vitro and in
      vivo. HK effectively suppressed the up-regulation of VDUP1 mRNA in CGNs
      undergoing apoptosis via Ca(2+) influx through voltage-dependent L-type Ca(2+)
      channels, which did not require de novo protein synthesis. The up-regulation
      occurred in parallel with that of the c-jun transcript and c-jun protein
      phosphorylation. Moreover, SB203580, p38 mitogen-activated protein kinase
      inhibitor, suppressed up-regulation of both c-jun and VDUP1 mRNAs, and c-jun
      phosphorylation in CGNs undergoing apoptosis. IGF-1, one of the neuroprotective
      agents for CGNs, also inhibited VDUP1 mRNA up-regulation through a
      phosphoinositide 3 kinase-dependent pathway. These results suggest that the VDUP1
      gene is a novel member of early response genes in neuronal apoptosis whose
      expression is directly regulated by Ca(2+) influx and coordinately regulated with
      the transcription factor c-jun in CGNs.

PMID- 11579136
TI  - Intracellular neuronal calcium sensor (NCS) protein VILIP-1 modulates cGMP
      signalling pathways in transfected neural cells and cerebellar granule neurones.
AB  - The family of intracellular neuronal calcium-sensors (NCS) belongs to the
      superfamily of EF-hand proteins. Family members have been shown by in vitro
      assays to regulate signal cascades in retinal photoreceptor cells. To study the
      functions of NCS proteins not expressed in photoreceptor cells we examined
      Visinin-like protein-1 (VILIP-1) effects on signalling pathways in living neural
      cells. Visinin-like protein-1 expression increased cGMP levels in transfected C6
      and PC12 cells. Interestingly, in transfected PC12 cells stimulation was
      dependent on the subcellular localization of VILIP-1. In cells transfected with
      membrane-associated wild-type VILIP-1 particulate guanylyl cyclase (GC) was
      stimulated more strongly than soluble GC. In contrast, deletion of the N-terminal
      myristoylation site resulted in cytosolic localization of VILIP-1 and enhanced
      stimulation of soluble GC. To study the molecular mechanisms underlying GC
      stimulation VILIP-1 was examined to see if it can physically interact with GCs. A
      direct physical interaction of VILIP-1 with the recombinant catalytic domain of
      particulate GCs-A, B and with native GCs enriched from rat brain was observed in
      GST pull-down as well as in surface plasmon resonance interaction studies.
      Furthermore, following trituration of recombinant VILIP-1 protein into cerebellar
      granule cells the protein influenced only signalling by GC-B. Together with the
      observed colocalization of GC-B, but not GC-A, with VILIP-1 in cerebellar granule
      cells, these results suggest that VILIP-1 may be a physiological regulator of GC
      B.

PMID- 11579137
TI  - Neuroprotection of striatal neurons against kainate excitotoxicity by
      neurotrophins and GDNF family members.
AB  - Neurotrophic factors are regarded as potential therapeutic tools in
      neurodegenerative disorders. Here, we analysed the protective effects of brain
      derived neurotrophic factor, neurotrophin-3, glial cell line-derived neurotrophic
      factor and neurturin against the excitotoxic damage induced by kainate in
      striatal neurons in vitro and in vivo. Our results show that the decrease in the
      number of cultured striatal calbindin-positive neurons induced by kainate was
      prevented by treatment with any of these factors. To characterize their
      protective effects in vivo, cell lines overexpressing brain-derived neurotrophic
      factor, neurotrophin-3, glial cell line-derived neurotrophic factor or neurturin
      were grafted into the striatum. We found that the numbers of striatal projection
      neurons (calbindin-positive) and striatal interneurons (parvalbumin- or choline
      acetyltransferase-positive) were differentially decreased after kainate lesion.
      These neurotrophic factors prevented the loss of striatal projection neurons and
      interneurons with differing efficiency: brain-derived neurotrophic factor was the
      most efficient, whereas neurturin was the least. Our findings show that brain
      derived neurotrophic factor, neurotrophin-3, glial cell line-derived neurotrophic
      factor and neurturin have specific neuroprotective profiles in striatal neurons
      and indicate that they are specific modulators of the survival of distinct
      subsets of striatal neurons in pathophysiological conditions.

PMID- 11579138
TI  - Accumulation of non-erythroid alpha II-spectrin and calpain-cleaved alpha II
      spectrin breakdown products in cerebrospinal fluid after traumatic brain injury
      in rats.
AB  - Although a number of increased CSF proteins have been correlated with brain
      damage and outcome after traumatic brain injury (TBI), a major limitation of
      currently tested biomarkers is a lack of specificity for defining
      neuropathological cascades. Identification of surrogate biomarkers that are
      elevated in CSF in response to brain injury and that offer insight into one or
      more pathological neurochemical events will provide critical information for
      appropriate administration of therapeutic compounds for treatment of TBI
      patients. Non-erythroid alpha II-spectrin is a cytoskeletal protein that is a
      substrate of both calpain and caspase-3 cysteine proteases. As we have previously
      demonstrated, cleavage of alpha II-spectrin by calpain and caspase-3 results in
      accumulation of protease-specific spectrin breakdown products (SBDPs) that can be
      used to monitor the magnitude and temporal duration of protease activation.
      However, accumulation of alpha II-spectrin and alpha II-SBDPs in CSF after TBI
      has never been examined. Following a moderate level (2.0 mm) of controlled
      cortical impact TBI in rodents, native alpha II-spectrin protein was decreased in
      brain tissue and increased in CSF from 24 h to 72 h after injury. In addition,
      calpain-specific SBDPs were observed to increase in both brain and CSF after
      injury. Increases in the calpain-specific 145 kDa SBDP in CSF were 244%, 530% and
      665% of sham-injured control animals at 24 h, 48 h and 72 h after TBI,
      respectively. The caspase-3-specific SBDP was observed to increase in CSF in some
      animals but to a lesser degree. Importantly, levels of these proteins were
      undetectable in CSF of uninjured control rats. These results indicate that
      detection of alpha II-spectrin and alpha II-SBDPs is a powerful discriminator of
      outcome and protease activation after TBI. In accord with our previous studies,
      results also indicate that calpain may be a more important effector of cell death
      after moderate TBI than caspase-3.

PMID- 11579139
TI  - The neuroprotective agent ebselen modifies NMDA receptor function via the redox
      modulatory site.
AB  - Ebselen is a seleno-organic compound currently in clinical trials for the
      treatment of ischemic stroke and subarachnoid hemorrhage. Its putative mode of
      action as a neuroprotectant is via cyclical reduction and oxidation reactions, in
      a manner akin to glutathione peroxidase. For this reason, we have investigated
      the effects of ebselen on the redox-sensitive NMDA receptor. We have found that
      ebselen readily reversed dithiothreitol (DTT) potentiation of NMDA-mediated
      currents in cultured neurons and in Chinese hamster ovary (CHO) cells expressing
      wild-type NMDA NR1/NR2B receptors. In contrast, ebselen was unable to modulate
      NMDA-induced currents in neurons previously exposed to the thiol oxidant 5,5'
      dithiobis(2-nitrobenzoic acid) (DTNB), or in CHO cells expressing a mutant
      receptor lacking the NR1 redox modulatory site, suggesting that ebselen oxidizes
      the NMDA receptor via this site. In addition, ebselen was substantially less
      effective in modifying NMDA responses in neurons exposed to alkylating agent N
      ethylmaleimide (NEM) following DTT treatment. Ebselen also reversed DTT block of
      carbachol-mediated currents in Cos-7 cells expressing the alpha(2)beta delta
      epsilon subunits of the acetylcholine receptor, an additional redox-sensitive ion
      channel. Ebselen was observed to significantly increase cell viability following
      a 30-min NMDA exposure in cultured neurons. In contrast, other more typical
      antioxidant compounds did not afford neuroprotection in a similar paradigm. We
      conclude that ebselen may be neuroprotective in part due to its actions as a
      modulator of the NMDA receptor redox modulatory site.

PMID- 11579140
TI  - Pro-inflammatory and pro-oxidant properties of the HIV protein Tat in a
      microglial cell line: attenuation by 17 beta-estradiol.
AB  - Microglia are activated in humans following infection with human immunodeficiency
      virus (HIV), and brain inflammation is thought to be involved in neuronal injury
      and dysfunction during HIV infection. Numerous studies indicate a role for the
      HIV regulatory protein Tat in HIV-related inflammatory and neurodegenerative
      processes, although the specific effects of Tat on microglial activation, and the
      signal transduction mechanisms thereof, have not been elucidated. In the present
      study, we document the effects of Tat on microglial activation and characterize
      the signal transduction pathways responsible for Tat's pro-inflammatory effects.
      Application of Tat to N9 microglial cells increased multiple parameters of
      microglial activation, including superoxide production, phagocytosis, nitric
      oxide release and TNF alpha release. Tat also caused activation of both p42/p44
      mitogen activated protein kinase (MAPK) and NF kappa B pathways. Inhibitor
      studies revealed that Tat-induced NF kappa B activation was responsible for
      increased nitrite release, while MAPK activation mediated superoxide release, TNF
      alpha release, and phagocytosis. Lastly, pre-treatment of microglial cells with
      physiological concentrations of 17 beta-estradiol suppressed Tat-mediated
      microglial activation by interfering with Tat-induced MAPK activation. Together,
      these data elucidate specific components of the microglial response to Tat and
      suggest that Tat could contribute to the neuropathology associated with HIV
      infection through microglial promulgation of oxidative stress.

PMID- 11579141
TI  - Agonists of the P2Y(AC)-receptor activate MAP kinase by a ras-independent pathway
      in rat C6 glioma.
AB  - We have previously shown that an ecto-NPPase modulates the ATP- and ADP-mediated
      P2Y(AC)-receptor activation in rat C6 glioma. In the present study, 2MeSADP and
      Ap(3)A induced no detectable PI turnover and were identified as specific agonists
      of the P2Y(AC)-receptor with EC(50) values of 250 +/- 37 pM and 1 +/- 0.5 microM,
      respectively. P2Y(AC)-receptor stimulation increased MAP kinase (ERK1/2)
      activation that returned to the basal level 4 h after stimulation and was
      correlated with a gradual desensitization of the P2Y(AC)-purinoceptor. The
      purinoceptor antagonists DIDS and RB2 blocked MAP kinase activation. An IP(3)
      independent Ca(2+)-influx was observed after P2Y(AC)-receptor activation.
      Inhibition of this influx by Ca(2+)-chelation, did not affect MAP kinase
      activation. Pertussis toxin, toxin B, selective PKC-inhibitors and a specific MEK
      inhibitor inhibited the 2MeSADP- and Ap(3)A-induced MAP kinase activation. In
      addition, transfection with dominant negative RhoA(Asn19) rendered C6 cells
      insensitive to P2Y(AC)-receptor-mediated MAP kinase activation whereas dominant
      negative ras was without effect. Immunoprecipitation experiments indicated a
      significant increase in the phosphorylation of raf-1 after P2Y(AC)-receptor
      activation. We may conclude that P2Y(AC)-purinoceptor agonists activate MAP
      kinase through a G(i)-RhoA-PKC-raf-MEK-dependent, but ras- and Ca(2+)-independent
      cascade.

PMID- 11579142
TI  - Mechanisms underlying extracellular ATP-evoked interleukin-6 release in mouse
      microglial cell line, MG-5.
AB  - Microglia play various important roles in the CNS via the synthesis of cytokines.
      The ATP-evoked production of interleukin-6 (IL-6) and its intracellular signals
      were examined using a mouse microglial cell line, MG-5. ATP, but not its
      metabolites, produced IL-6 in a concentration-dependent manner. Although ATP
      activated two mitogen-activated protein kinases, i.e. p38 and extracellular
      signal-regulated protein kinase, only p38 was involved in the IL-6 induction.
      However, the activation of p38 was not sufficient for the IL-6 induction because
      2'- and 3'-O-(4-benzoylbenzoyl) ATP, an agonist to P2X7 receptors, failed to
      produce IL-6 despite the fact that it activated p38. Unlike in other cytokines in
      microglial cells, P2Y rather than P2X7 receptors seem to have a major role in the
      IL-6 production by the cells. The ATP-evoked IL-6 production was attenuated by
      Go6976, an inhibitor of Ca(2+)-dependent protein kinase C (PKC). The P2Y receptor
      responsible for these responses was insensitive to pertussis toxin (PTX) and was
      linked to phospholipase C. Taken together, ATP acting on PTX-insensitive P2Y
      receptors activates p38 and Ca(2+)-dependent PKC, thereby resulting in the mRNA
      expression and release of IL-6 in MG-5. This is a novel pathway for the induction
      of cytokines in microglia.

PMID- 11579143
TI  - Retinal phospholipase C from squid is a regulator of Gq alpha GTPase activity.
AB  - The phospholipase C (PLC) pathway is the major signaling mechanism of
      photoactivation in invertebrate photoreceptors. Here we report the cloning of a
      cDNA encoding a 140-kDa retinal PLC that is uniquely expressed in squid
      photoreceptors. This cDNA encodes a protein with multiple distinct modular
      domains: PH, X and Y catalytic, and C2 domains, as well as G- and P-box motifs
      and two GTP/ATP binding motifs. The PLC was stimulated by activated squid Gq
      alpha but not by squid Gq beta gamma or mammalian beta gamma subunits. The PLC
      was inhibited by monophosphate, diphosphate and triphosphate nucleotides but not
      cyclic nucleosides. We also tested the ability of PLC-140 to regulate the GTPase
      activity of Gq alpha in the rhabdomeric membranes. Depletion of PLC-140 from the
      rhabdomeric membranes decreased the GTP hydrolysis but not GTP gamma S binding to
      the membranes. Reconstitution of purified PLC-140 with membranes accelerated Gq
      alpha GTPase activity by fivefold at a concentration of 2.5 microM. Our data
      suggest that PLC-140 plays an important role in both the activation and
      inactivation pathways of invertebrate visual transduction.

PMID- 11579144
TI  - Photoaffinity labeling of insect nicotinic acetylcholine receptors with a novel
      [(3)H]azidoneonicotinoid.
AB  - The nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel in the
      insect CNS and a target for major insecticides. Here we use photoaffinity
      labeling to approach the functional architecture of insect nAChRs. Two candidate
      5-azido-6-chloropyridin-3-yl photoaffinity probes are evaluated for their
      receptor potencies: azidoneonicotinoid (AzNN) with an acyclic nitroguanidine
      moiety; azidodehydrothiacloprid. Compared to their non-azido parents, both probes
      are of decreased potencies at Drosophila (fruit fly) and Musca (housefly)
      receptors but AzNN retains full potency at the Myzus (aphid) receptor. [(3)H]AzNN
      was therefore radiosynthesized at high specific activity (84 Ci/mmol) as a novel
      photoaffinity probe. [(3)H]AzNN binds to a single high-affinity site in Myzus
      that is competitively inhibited by imidacloprid and nicotine and further
      characterized as to its pharmacological profile with various nicotinic ligands.
      [(3)H]AzNN photoaffinity labeling of Myzus and Homalodisca (leafhopper) detects a
      single radiolabeled peak in each case displaceable with imidacloprid and nicotine
      and with molecular masses corresponding to approximately 45 and approximately 56
      kDa, respectively. The photoaffinity-labeled receptor in both Drosophila and
      Musca has imidacloprid- and nicotine-sensitive profiles and migrates at
      approximately 66 kDa. These photoaffinity-labeled polypeptides are considered to
      be the insecticide-binding subunits of native insect nAChRs.

PMID- 11579145
TI  - Nicotinic acetylcholine receptors containing alpha 7 subunits on rat cortical
      neurons do not undergo long-lasting inactivation even when up-regulated by
      chronic nicotine exposure.
AB  - Chronic exposure to (-)nicotine has been widely reported to up-regulate nicotinic
      acetylcholine receptors on neurons and induce long-term inactivation as a
      possible cause. Nicotinic receptors containing alpha 7 subunits are among the
      most abundant in brain and influence diverse cellular events. Whole-cell patch
      clamp recording from embryonic rat cortical neurons in culture was used to
      identify responses from alpha 7-containing receptors. Immunochemical staining for
      glutamic acid decarboxylase (GAD) indicated that both GABAergic and non-GABAergic
      neurons expressed the receptors. Exposure to micromolar concentrations of
      nicotine for 1-4 days caused up-regulation of the receptors as measured by [alpha
      (125)I]-bungarotoxin binding. Carbachol produced the same up-regulation, and cell
      counts demonstrated that neuronal survival was unchanged. The up-regulation was
      accompanied by an increased whole-cell response; no evidence was found for long
      lasting inactivation. Autonomic alpha 7-containing receptors also avoided long
      lasting inactivation, even though the receptors were down-regulated by nicotine.
      Blocking protein synthesis or protein glycosylation prevented receptor up
      regulation on cortical neurons, suggesting that new synthesis was required. No
      evidence was found for a pre-existing intracellular pool that supplied receptors
      to the surface. The results indicate that alpha 7-containing receptors differ
      from other receptor subtypes in their regulation by nicotine and demonstrate
      further that long-lasting inactivation is not an obligatory requirement for up
      regulation in this case.

PMID- 11579146
TI  - Interaction of a glucocorticoid-responsive element with regulatory sequences in
      the promoter region of the mouse tyrosine hydroxylase gene.
AB  - The purpose of the work reported here was to determine whether the tyrosine
      hydroxylase glucocorticoid-responsive element (TH-GRE) interacts with the cyclic
      AMP pathway and the CRE in regulating mouse TH promoter activity, and whether an
      additional, previously identified downstream GRE-like element also participates
      in the function of the TH-GRE and CRE. To determine the role of the cAMP pathway
      on TH-GRE function, we compared the effects of forskolin and dexamethasone on TH
      mRNA, TH gene transcription and TH promoter activity in a mutant PC12 cell line
      (A126-1B2) deficient in cAMP-dependent protein kinase A (PKA) with their effects
      in the wild-type parental strain. Forskolin treatment increased TH mRNA content,
      transcriptional activity and the activity of a chimeric gene with 3.6 kb of the
      TH promoter in wild-type cells, but not in PKA-deficient cells. In contrast,
      dexamethasone treatment stimulated equivalent increases in TH mRNA, TH gene
      transcription and TH promoter activity in each cell type. Mutation of the CRE in
      chimeric constructs containing 3.6 kb of the 5' flanking sequence of the mouse TH
      gene or coexpression of a dominant-negative mutant of CREB prevented the
      stimulation of TH promoter activity by forskolin. However, neither the mutation
      of the CRE nor inhibition of CREB influenced basal or dexamethasone-stimulated
      promoter activity. Site-directed mutagenesis of the TH-GRE eliminated the
      response of the promoter to dexamethasone. However, the mutagenesis of a more
      proximal 15-bp region with a GRE-like sequence had no demonstrable effect on the
      ability of dexamethasone to stimulate TH promoter activity. Neither mutagenesis
      of the TH-GRE or the downstream GRE-like sequence had an effect on the ability of
      forskolin to activate this chimeric gene. Taken together, these results provide
      evidence that a single GRE is sufficient for maximal induction of transcriptional
      activity by glucocorticoids and that the CRE is not required for either partial
      or full activity of this upstream GRE sequence.

PMID- 11579147
TI  - Increased infarct size and exacerbated apoptosis in the glutathione peroxidase-1
      (Gpx-1) knockout mouse brain in response to ischemia/reperfusion injury.
AB  - Glutathione peroxidase is an antioxidant enzyme that is involved in the control
      of cellular oxidative state. Recently, unregulated oxidative state has been
      implicated as detrimental to neural cell viability and involved in both acute and
      chronic neurodegeneration. In this study we have addressed the importance of a
      functional glutathione peroxidase in a mouse ischemia/reperfusion model. Two
      hours of focal cerebral ischemia followed by 24 h of reperfusion was induced via
      the intraluminal suture method. Infarct volume was increased three-fold in the
      glutathione peroxidase-1 (Gpx-1) -/- mouse compared with the wild-type mouse;
      this was mirrored by an increase in the level of apoptosis found at 24 h in the
      Gpx-1 -/- mouse compared with the wild-type mouse. Neuronal deficit scores
      correlated to the histologic data. We also found that activated caspase-3
      expression is present at an earlier time point in the Gpx-1 -/- mice when
      compared with the wild-type mice, which suggests an enhanced susceptibility to
      apoptosis in the Gpx-1 -/- mouse. This is the first known report of such a
      dramatic increase, both temporally and in level of apoptosis in a mouse stroke
      model. Our results suggest that Gpx-1 plays an important regulatory role in the
      protection of neural cells in response to the extreme oxidative stress that is
      released during ischemia/reperfusion injury.

PMID- 11579148
TI  - Aberrant metal binding by prion protein in human prion disease.
AB  - Human prion diseases are characterized by the conversion of the normal prion
      protein (PrP(C)) into a pathogenic isomer (PrP(Sc)). Distinct PrP(Sc) conformers
      are associated with different subtypes of prion diseases. PrP(C) binds copper and
      has antioxidation activity. Changes in metal-ion occupancy can lead to
      significant decline of the antioxidation activity and changes in conformation of
      the protein. We studied the trace element status of brains from patients with
      sporadic Creutzfeldt-Jakob disease (sCJD). We found a decrease of up to 50% of
      copper and an increase in manganese of approximately 10-fold in the brain tissues
      from sCJD subjects. We have also studied the metal occupancy of PrP in sCJD
      patients. We observed striking elevation of manganese and, to a lesser extent, of
      zinc accompanied by significant reduction of copper bound to purified PrP in all
      sCJD variants, determined by the PrP genotype and PrP(Sc) type, combined. Both
      zinc and manganese were undetectable in PrP(C) preparations from controls. Copper
      and manganese changes were pronounced in sCJD subjects homozygous for methionine
      at codon 129 and carrying PrP(Sc) type-1. Anti-oxidation activity of purified PrP
      was dramatically reduced by up to 85% in the sCJD variants, and correlated with
      increased in oxidative stress markers in sCJD brains. These results suggest that
      altered metal-ion occupancy of PrP plays a pivotal role in the pathogenesis of
      prion diseases. Since the metal changes differed in each sCJD variants, they may
      contribute to the diversity of PrP(Sc) and disease phenotype in sCJD. Finally,
      this study also presented two potential approaches in the diagnosis of CJD; the
      significant increase in brain manganese makes it potentially detectable by MRI,
      and the binding of manganese by PrP in sCJD might represent a novel diagnostic
      marker.

PMID- 11579149
TI  - Tetracycline derivatives and ceftriaxone, a cephalosporin antibiotic, protect
      neurons against apoptosis induced by ionizing radiation.
AB  - DNA damage induced by low doses of ionizing radiation causes apoptosis, which is
      partially mediated via the generation of free radicals. Both free radicals and
      apoptosis are involved in the majority of brain diseases, including stroke,
      Alzheimer's disease and amyotrophic lateral sclerosis. Because previous studies
      have shown that tetracycline derivatives doxycycline and minocycline have anti
      inflammatory effects and are protective against brain ischemia, we studied
      whether minocycline and doxycycline or ceftriaxone, a cephalosporin antibiotic
      with the potential to inhibit excitotoxicity, protect neurons against ionizing
      radiation in primary cortical cultures. A single dose of 1 Gy significantly
      increased lactate dehydrogenase release, induced DNA fragmentation in neurons and
      triggered microglial proliferation. Treatment with minocycline (20 nM),
      doxycycline (20 nM) and ceftriaxone (1 microM) significantly reduced irradiation
      induced lactate dehydrogenase release and DNA fragmentation. The most efficient
      protection was achieved by minocycline treatment, which also inhibited the
      irradiation-induced increase in microglial cell number. Our results suggest that
      some tetracycline derivatives, such as doxycycline and minocycline, and
      ceftriaxone, a cephalosporin derivative, protect neurons against apoptotic death.

PMID- 11579150
TI  - Anandamide, but not 2-arachidonoylglycerol, accumulates during in vivo
      neurodegeneration.
AB  - Endogenous cannabinoid receptor ligands (endocannabinoids) may rescue neurons
      from glutamate excitotoxicity. As these substances also accumulate in cultured
      immature neurons following neuronal damage, elevated endocannabinoid
      concentrations may be interpreted as a putative neuroprotective response.
      However, it is not known how glutamatergic insults affect in vivo endocannabinoid
      homeostasis, i.e. N-arachidonoylethanolamine (anandamide) and 2
      arachidonoylglycerol (2-AG), as well as other constituents of their lipid
      families, N-acylethanolamines (NAEs) and 2-monoacylglycerols (2-MAGs),
      respectively. Here we employed three in vivo neonatal rat models characterized by
      widespread neurodegeneration as a consequence of altered glutamatergic
      neurotransmission and assessed changes in endocannabinoid homeostasis. A 46-fold
      increase of cortical NAE concentrations (anandamide, 13-fold) was noted 24 h
      after intracerebral NMDA injection, while less severe insults triggered by mild
      concussive head trauma or NMDA receptor blockade produced a less pronounced NAE
      accumulation. By contrast, levels of 2-AG and other 2-MAGs were virtually
      unaffected by the insults employed, rendering it likely that key enzymes in
      biosynthetic pathways of the two different endocannabinoid structures are not
      equally associated to intracellular events that cause neuronal damage in vivo.
      Analysis of cannabinoid CB(1) receptor mRNA expression and binding capacity
      revealed that cortical subfields exhibited an up-regulation of these parameters
      following mild concussive head trauma and exposure to NMDA receptor blockade.
      This may suggest that mild to moderate brain injury may trigger elevated
      endocannabinoid activity via concomitant increase of anandamide levels, but not 2
      AG, and CB(1) receptor density.

PMID- 11579151
TI  - Lactate doesn't necessarily cause fatigue: why are we surprised?

PMID- 11579152
TI  - Making sense of oxygen sensing.

PMID- 11579153
TI  - Potentiation and inhibition of Ca(2+) release-activated Ca(2+) channels by 2
      aminoethyldiphenyl borate (2-APB) occurs independently of IP(3) receptors.
AB  - 1. The effects of the IP(3)-receptor antagonist 2-aminoethyldiphenyl borate (2
      APB) on the Ca(2+) release-activated Ca(2+) current (I(CRAC)) in Jurkat human T
      cells, DT40 chicken B cells and rat basophilic leukaemia (RBL) cells were
      examined. 2. 2-APB elicited both stimulatory and inhibitory effects on Ca(2+)
      influx through CRAC channels. At concentrations of 1-5 microM, 2-APB enhanced
      Ca(2+) entry in intact cells and increased I(CRAC) amplitude by up to fivefold.
      At levels > or = 10 microM, 2-APB caused a transient enhancement of I(CRAC)
      followed by inhibition. 3. 2-APB altered the kinetics of fast Ca(2+)-dependent
      inactivation of I(CRAC). At concentrations of 1-5 microM, 2-APB increased the
      rate of fast inactivation. In contrast, 2-APB at higher concentrations (> or = 10
      microM) reduced or completely blocked inactivation. 4. 2-APB inhibited Ca(2+)
      efflux from mitochondria. 5. 2-APB inhibited I(CRAC) more potently when applied
      extracellularly than intracellularly. Furthermore, increased protonation of 2-APB
      at low pH did not affect potentiation or inhibition. Thus, 2-APB may have an
      extracellular site of action. 6. Neither I(CRAC) activation by passive store
      depletion nor the effects of 2-APB were altered by intracellular dialysis with
      500 microg ml(-1) heparin. 7. I(CRAC) is present in wild-type as well as mutant
      DT40 B cells lacking all three IP(3) receptor isoforms. 2-APB also potentiates
      and inhibits I(CRAC) in both cell types, indicating that 2-APB exerts its effects
      independently of IP(3) receptors. 8. Our results show that CRAC channel
      activation does not require physical interaction with IP(3) receptors as proposed
      in the conformational coupling model. Potentiation of I(CRAC) by 2-APB may be a
      useful diagnostic feature for positive identification of putative CRAC channel
      genes, and provides a novel tool for exploring the physiological functions of
      store-operated channels.

PMID- 11579154
TI  - Contribution of L-type Ca(2+) channels to evoked transmitter release in cultured
      Xenopus nerve-muscle synapses.
AB  - 1. Simultaneous pre- and postsynaptic patch recordings were obtained from the
      varicosity synapses formed by Xenopus motoneurons on muscle cells in embryonic
      cultures, in order to elucidate the contribution of N- and L-type Ca(2+) channels
      to the varicosity Ca(2+) current (I(Ca)) and evoked transmitter release. 2.
      Although N-type channels are predominant in the varicosities and generally
      thought to be responsible for all evoked release, in most synapses a fraction of
      I(Ca) and release could be reversibly blocked by the L-type channel antagonist
      nifedipine, and enhanced by the agonist Bay K8644. Up to 50 % (mean, 21 %) of the
      I(Ca) evoked by a voltage clamp waveform mimicking a normal presynaptic action
      potential (APWF) is composed of L-type current. 3. Surprisingly, the nifedipine
      sensitive (L) channels activated more rapidly (time-constant, 0.46 ms at +30 mV)
      than the nifedipine-insensitive (N) channels (time constant, 1.42 ms). Thus the L
      type current would play a disproportionate role in the I(Ca) linked to a normal
      action potential. 4. The relationship between I(Ca) and release was the same for
      nifedipine-sensitive and -resistant components. The N- and L-components of I(Ca)
      are thus equally potent in evoking release. This may represent an immature stage
      before N-type channels become predominant. 5. Replacing Ca(2+) in the medium with
      Ba(2+) strongly enhanced the L-type component, suggesting that L-type channels
      may be inactivated at Ca(2+) levels close to those at rest. 6. We speculate that
      populations of L-type channels in different parts of the neuron may be recruited
      or inactivated by fluctuations of the cytosolic Ca(2+) concentration within the
      physiological range.

PMID- 11579155
TI  - Nociceptin inhibits calcium channel currents in a subpopulation of small
      nociceptive trigeminal ganglion neurons in mouse.
AB  - 1. The effects of nociceptin/orphanin FQ (N/OFQ) and opioid receptor agonists on
      voltage-activated calcium channel currents (I(Ca)) were examined in acutely
      isolated mouse trigeminal ganglion neurons using whole-cell patch-clamp
      recordings. These effects were correlated with responses of the neurons to
      capsaicin and binding of Bandeiraea simplicifolia isolectin B4 (IB4). 2.
      Trigeminal neurons were divided into two populations based on the presence (type
      2) or absence (type 1) of a prominent T-type I(Ca). N/OFQ potently (EC(50) of 19
      nM) inhibited high-voltage-activated (HVA) I(Ca) in most (82 %) small
      (capacitance < 12 pF) type 1 neurons, but few (9 %) larger (> 12 pF) type 1
      neurons. N/OFQ inhibited I(Ca) in few (23 %) type 2 cells, and did not affect the
      T-type I(Ca) in any cell. 3. The mu-opioid agonists DAMGO and morphine inhibited
      I(Ca) in most type 1 neurons, more often (95 % versus 77 %) in the small cells.
      The inhibition of I(Ca) by DAMGO and morphine was more efficacious in small
      versus large type 1 neurons. mu-Opioids did not inhibit I(Ca) in type 2 neurons.
      4. Most small type 1 neurons were sensitive to capsaicin (93 %) and bound IB4 (86
      %). Fewer larger type 1 neurons responded to capsaicin (30 %) or bound IB4 (58
      %). Type 2 neurons did not respond to capsaicin, although some bound IB4 (35 %).
      5. Thus, N/OFQ preferentially inhibits HVA I(Ca) in a subpopulation of small
      nociceptive trigeminal ganglion neurons that is also highly sensitive to mu
      opioid agonists.

PMID- 11579156
TI  - Rapidly inactivating and non-inactivating calcium-activated potassium currents in
      frog saccular hair cells.
AB  - 1. Using a semi-intact epithelial preparation we examined the Ca(2+)-activated
      K(+) (K(Ca)) currents of frog (Rana pipiens) saccular hair cells. After blocking
      voltage-dependent K(+) (K(V)) currents with 4-aminopyridine (4-AP) an outward
      current containing inactivating (I(transient)) and non-inactivating (I(steady))
      components remained. 2. The contribution of each varied greatly from cell to
      cell, with I(transient) contributing from 14 to 90 % of the total outward
      current. Inactivation of I(transient) was rapid (tau approximately 2-3 ms) and
      occurred within the physiological range of membrane potentials (V(1/2) = -63 mV).
      Recovery from inactivation was also rapid (tau approximately 10 ms). 3.
      Suppression of both I(transient) and I(steady) by depolarizations that approached
      the Ca(2+) equilibrium potential and by treatments that blocked Ca(2+) influx
      (application Ca(2+)-free saline or Cd(2+)), suggest both are Ca(2+) dependent.
      Both were blocked by iberiotoxin, a specific blocker of large-conductance K(Ca)
      channels (BK), but not by apamin, a specific blocker of small-conductance K(Ca)
      channels. 4. Ensemble-variance analysis showed that I(transient) and I(steady)
      flow through two distinct populations of channels, both of which have a large
      single-channel conductance (~100 pS in non-symmetrical conditions). Together,
      these data indicate that both I(transient) and I(steady) are carried through BK
      channels, one of which undergoes rapid inactivation while the other does not. 5.
      Inactivation of I(transient) could be removed by extracellular papain and could
      later be restored by intracellular application of the 'ball' domain of the
      auxiliary subunit (beta2) thought to mediate BK channel inactivation in rat
      chromaffin cells. We hypothesize that I(transient) results from the association
      of a similar beta subunit with some of the BK channels and that papain removes
      inactivation by cleaving extracellular sites required for this association.

PMID- 11579157
TI  - Cell-to-cell communication via nitric oxide modulation of oscillatory Cl(-)
      currents in rat intact cerebral arterioles.
AB  - 1. Diffusion-mediated changes in ion channel function within blood vessels have
      not been demonstrated directly in a patch-clamp study. Here, we examined the
      hypothesis that endothelium-derived diffusible bioactive substances would modify
      endothelin-1 (ET-1)-evoked membrane currents in smooth muscle cells situated
      within intact arterioles. 2. In pieces of arterioles dissected from the rat
      cerebral pial membrane, patch electrodes were placed on single smooth muscle
      cells identified under the microscope. Under perforated patch-clamp conditions,
      ET-1 evoked an oscillatory inward current at negative potentials in such cells in
      the presence of the gap junction disrupter 18alpha-glycyrrhetinic acid. ET-1 also
      elicited an oscillation superimposed on a membrane depolarization in current
      clamp mode. 3. The oscillatory current exhibited an outwardly rectifying current
      voltage relationship, a sensitivity to niflumic acid, a requirement for inositol
      1,4,5-trisphosphate (IP(3))- and caffeine-sensitive Ca(2+) stores and for
      external Ca(2+) and a rank order of anion permeabilities characteristic of Ca(2+)
      activated Cl(-) currents (I(Ca(Cl))). 4. This oscillatory response was inhibited
      by bradykinin (an effect distinct from the electrical propagation of
      hyperpolarization) and this effect was attenuated by the NO-synthase inhibitor
      N(omega)-nitro-L-arginine and by the NO scavenger oxyhaemoglobin but not by the
      cyclo-oxygenease inhibitor indomethacin. 8-Bromoguanosine 3',5'-cyclic
      monophosphate (8-Br-cGMP) and nitroprusside closely mimicked the effect of
      bradykinin. 5. The present patch-clamp study has revealed diffusion-mediated cell
      to-cell interaction in an intact blood vessel: bradykinin appears to cause NO to
      move from endothelium to smooth muscle, there to inhibit an ET-1-evoked
      oscillatory I(Ca(Cl)) via the NO-cGMP pathway.

PMID- 11579158
TI  - Okadaic acid-sensitive activation of Maxi Cl(-) channels by triphenylethylene
      antioestrogens in C1300 mouse neuroblastoma cells.
AB  - 1. The regulation of Maxi Cl(-) channels by 17beta-oestradiol and non-steroidal
      triphenylethylene antioestrogens represents a rapid, non-classical effect of
      these compounds. In the present study we have investigated the signalling
      pathways used for the regulation of Maxi Cl(-) channel activity by oestrogens and
      antioestrogens in C1300 neuroblastoma cells. 2. Whole-cell Maxi Cl(-) currents
      were readily and reversibly activated by tamoxifen, toremifene and the membrane
      impermeant ethyl-bromide tamoxifen, only when applied to the extracellular
      medium. 3. Pre-treatment of C1300 cells with oestrogen or cAMP prevented the
      antioestrogen-induced activation of Maxi Cl(-) channels. The inhibitory effect of
      17beta-oestradiol and cAMP was abolished by the kinase inhibitor staurosporine.
      4. Current activation was unaffected by the removal of intracellular Ca(2+) and
      Mg(2+), but was completely abolished in the presence of okadaic acid. These
      results are consistent with the participation of an okadaic acid-sensitive
      serine/threonine protein phosphatase in the activation of Maxi Cl(-) channels.
      However, neither oestrogen or antioestrogen treatment modified the total activity
      of the two major serine/threonine phosphatases, PP1 and PP2A, in C1300 cells. 5.
      Although the role of these Maxi Cl(-) channels remains unknown, our findings
      suggest strongly that their modulation by oestrogens and antioestrogens is linked
      to intracellular signalling pathways.

PMID- 11579159
TI  - Regulation of GABA release by nicotinic acetylcholine receptors in the neonatal
      rat hippocampus.
AB  - 1. The whole-cell configuration of the patch-clamp technique was used to study
      the modulation of giant depolarizing potentials (GDPs) by nicotinic acetylcholine
      receptors (nAChRs) in CA3 hippocampal neurons in slices from postnatal day (P) 2
      6 rats. 2. Bath application of nicotine increased GDP frequency in a
      concentration-dependent manner. For example, nicotine (0.5-1 microM) enhanced GDP
      frequency from 0.05 +/- 0.04 to 0.17 +/- 0.04 Hz. This effect was prevented by
      the broad-spectrum nicotinic receptor antagonist dihydro-beta-erythtroidine
      (DHbetaE, 50 microM) and partially antagonized by methyllycaconitine (MLA, 50 nM)
      a competitive antagonist of alpha7 nAChRs. GDP frequency was also enhanced by AR
      17779 (100 microM), a selective agonist of alpha7 nAChRs. 3. The GABA(A) receptor
      antagonist bicuculline (10 microM) and the non-NMDA glutamate receptor antagonist
      DNQX (20 microM) blocked GDPs and prevented the effects of nicotine on GDPs. In
      the presence of DNQX, nicotine increased GABA-mediated synaptic noise, indicating
      that this drug may have a direct effect on GABAergic interneurons. 4. Bath
      application of edrophonium (20 microM), a cholinesterase inhibitor, in the
      presence of atropine (1 microM), increased GDP frequency, indicating that nAChRs
      can be activated by ACh released from the septo-hippocampal fibres. This effect
      was prevented by DHbetaE (50 microM). 5. In the majority of neurons tested, MLA
      (50 nM) and DHbetaE (50 microM) reduced the frequency of GDPs with different
      efficacy: a reduction of 98 +/- 11 and 61 +/- 29 % was observed with DHbetaE and
      MLA, respectively. In a subset of cells (40 % in the case of MLA and 17 % in the
      case of DHbetaE) these drugs induced a twofold increase in GDP frequency. 6. It
      is suggested that, during development, nAChRs modulate the release of GABA,
      assessed as GDPs, through distinct nAChRs. The rise of intracellular calcium via
      nAChRs would further strengthen GABA-mediated oscillatory activity. This can be
      crucial for consolidation of synaptic contacts and for the fine-tuning of the
      developing hippocampus.

PMID- 11579160
TI  - Nicotine facilitates glycine release in the rat spinal dorsal horn.
AB  - 1. Nicotinic effects on glycine release were investigated in slices of lumbar
      spinal cord using conventional whole-cell recordings. In most of the substantia
      gelatinosa (SG) neurons tested, nicotine increased the frequency of the
      glycinergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs). In a
      smaller proportion, nicotine evoked not only this same presynaptic response but
      also a postsynaptic response. 2. Nicotinic facilitation of glycinergic mIPSCs was
      investigated in mechanically dissociated SG neurons using nystatin-perforated
      patch recordings. Nicotine (3 x 10(-6) to 10(-5) M) reversibly enhanced the
      frequency of glycinergic mIPSCs without altering their amplitudes, thus
      indicating that nicotine facilitates glycine release through a presynaptic
      mechanism. 3. Choline, a selective alpha7 subunit of nicotinic acetylcholine
      receptor (nAChR) agonist, had no effect on the mIPSC frequency while anatoxin A,
      a broad-spectrum agonist of nAChR, facilitated the mIPSC frequency. 4. alpha
      Bungarotoxin, a selective alpha7 subunit antagonist, failed to block the
      nicotinic facilitatory action. Mecamylamine, a broad-spectrum nicotinic
      antagonist, reversibly inhibited nicotinic action. Dihydro-beta-erythroidine, a
      selective antagonist of nAChRs containing alpha4-beta2 subunits, completely
      blocked nicotinic action. 5. Ca(2+)-free but not Cd(2+)-containing bath solutions
      blocked nicotinic actions. 6. We therefore conclude that nicotine facilitates
      glycine release in the substantia gelatinosa of the spinal dorsal horn via
      specific nAChRs containing alpha4-beta2 subunits. This action on a subset of
      presynaptic nAChRs may underlie nicotine's modulation of noxious signal
      transmission and provide a cellular mechanism for the analgesic function of
      nicotine.

PMID- 11579161
TI  - Indirect actions of bradykinin on neonatal rat dorsal root ganglion neurones: a
      role for non-neuronal cells as nociceptors.
AB  - 1. In this study we have investigated the action of bradykinin (Bk) on cultured
      neonatal rat dorsal root ganglion (DRG) cells, with the aim of elucidating
      whether the neuronal response to Bk is influenced by association with non
      neuronal satellite cells. 2. Bradykinin (100 nM) evoked an inward current (I(Bk))
      in 51 of 58 voltage clamped DRG neurones (holding potential (V(h)) = -80 mV) that
      were in contact with non-neuronal satellite cells. 3. Bradykinin failed to evoke
      an inward current in isolated DRG neurones (V(h) = -80 mV) that were not in
      contact with non-neuronal satellite cells (n = 41). 4. The lack of neuronal
      response to Bk was not influenced by time in culture. Bradykinin failed to evoke
      a response in isolated neurones through 1-5 days in culture. By contrast neurones
      in contact with satellite cells responded to Bk throughout the same time period.
      5. Failure of isolated neurones to respond to Bk was not due to the replating
      procedure or to selective subcellular distribution of receptors/ion channels to
      the processes rather than the somata of neurones. 6. Using Indo-1 AM
      microfluorimetry Bk (100 nM) was demonstrated to evoke an intracellular Ca(2+)
      increase (Ca(Bk)) in DRG neurones in contact with non-neuronal satellite cells
      and in isolated neurones. 7. These data suggest that the inward current response
      to Bk requires contact between DRG neurones and non-neuronal satellite cells.
      This implies an indirect mechanism of action for Bk via the non-neuronal cells,
      which may perform a nociceptive role. However, Bk can also act directly on the
      neurones, since it evokes Ca(Bk) in isolated neurones. The relationship between
      Ca(Bk) and the Bk-induced inward current is unknown at present.

PMID- 11579162
TI  - Catecholamines are not linked to myometrial phospholipase C and uterine
      contraction in late pregnant and parturient mouse.
AB  - 1. We investigated whether catecholamines through activation of alpha(1)
      adrenergic receptors (alpha(1)-AR) are involved in mouse uterine contraction at
      parturition. Myometrial phospholipase C (PLC) activity and uterine contraction
      were measured in response to noradrenaline (NA), the specific alpha(1)-AR agonist
      phenylephrine (Phe) and oxytocin (OT). 2. Using the reverse transcription
      polymerase chain reaction RT-PCR, we detected the alpha(1a)-AR subtype in late
      pregnant mouse myometrium. We also detected, by immunoblotting studies,
      PLCbeta(1), PLCbeta(3) and different alpha-subunits of pertussis toxin
      insensitive (Galpha(q/11)) and -sensitive G proteins (Galpha(o/i3),
      Galpha(i1/2)). 3. Phenylephrine and NA did not alter the myometrial inositol
      phosphate (InsP) production of late pregnant or parturient mouse. In similar
      conditions, OT increased InsP production in a dose-dependent manner. Consistent
      with these results, only OT (10 microM) recruited PLCbeta(1) and PLCbeta(3) to
      myometrial plasma membranes. The OT-induced InsP response was not altered by
      pertussis toxin (300 ng ml(-1), 2 h pretreatment), suggesting the involvement of
      a member of the Galpha(q) family. 4. Noradrenaline and Phe failed to increase
      uterine contraction at late pregnancy and at parturition. In contrast, OT induced
      uterine contraction in a dose-dependent manner with maximal increase (400 %) at a
      concentration of 1 microM. 5. The results indicate that OT receptors (OTR) but
      not alpha(1)-AR are linked to myometrial PLC activation and uterine contraction
      in late pregnant and parturient mouse. This discrepancy between mouse and other
      mammals could be attributed to the alpha(1)-AR subtype expressed in myometrium at
      this time.

PMID- 11579163
TI  - Nitric oxide contracts longitudinal smooth muscle of opossum oesophagus via
      excitation-contraction coupling.
AB  - 1. The effects of sodium nitroprusside (SNP) and diethylenetriamine/nitric oxide
      adduct (DETA/NO), putative nitric oxide (NO) donors, on opossum oesophageal
      longitudinal smooth muscle were investigated using isometric tension and
      intracellular micro-electrode recordings. 2. SNP produced concentration-dependent
      contractions of oesophageal longitudinal smooth muscle with an EC(50) of 239.6 +/
      78.2 microM (mean +/- S.E.M., n = 10). Maximal contraction induced by SNP (1 mM)
      was about 75.5 +/- 8.5 % (n = 10) of the 60 mM KCl-induced contraction. The SNP
      induced contraction was resistant to tetrodotoxin (TTX; 1 microM), but abolished
      by nifedipine (1 microM), as well as by niflumic acid (300 microM) and 9-anthroic
      acid (9-AC; 1 mM), Ca(2+)-activated Cl(-) channel blockers. 3. DETA/NO at
      concentrations of 100 and 500 microM induced 83.1 +/- 24.4 and 104.1 +/- 34.9 %
      of the 60 mM KCl-induced contraction (n = 4), respectively, which was abolished
      by nifedipine (1 microM), niflumic acid (300 microM) and 9-AC (1 mM). 4. Pre
      application of 1H-[1,2,4]oxidiazolo[4,3,-alpha]quinoxalin-1-one (ODQ) (10
      microM), a guanylate cyclase inhibitor, significantly inhibited the SNP-induced
      contraction, whereas 8-bromo-cGMP (1 mM), a membrane-permeable analogue of cGMP,
      mimicked the SNP-induced contraction. 5. Intracellular recordings revealed that
      SNP (300 microM) depolarized resting membrane potentials (RMPs) and increased the
      frequency of spontaneous spike-like action potentials. However, these electrical
      alterations were eliminated by pretreatment with niflumic acid (300 microM). 6.
      These results suggest that NO produces an excitation-contraction coupling in
      opossum oesophageal longitudinal smooth muscle via a cGMP-dependent signalling
      pathway. This contraction depends on extracellular Ca(2+) entry through
      activation of L-type Ca(2+) channels.

PMID- 11579164
TI  - Glucose effects on gastric motility and tone evoked from the rat dorsal vagal
      complex.
AB  - 1. To examine the effects of glucose on the central components of the vago-vagal
      reflex control of gastric function, we performed both in vivo and in vitro
      experiments on neurones in the medial nucleus of the tractus solitarius (mNTS)
      and in the dorsal motor nucleus of the vagus (DMV). 2. In the in vivo
      anaesthetized rat preparation, unilateral microinjection of D-glucose (10 or 50
      mM (60 nl)(-1)) in mNTS produced inhibition of gastric motility and an increase
      in intragastric pressure. D-glucose had no effect in the DMV. 3. In the in vitro
      rat brainstem slice preparation, whole-cell recordings of DMV neurones showed
      that increasing the glucose concentration of the perfusion solution from 5 mM to
      15 or 30 mM produced outward currents of 35 +/- 5 pA (n = 7) and 51 +/- 10 pA (n
      = 11), respectively. These were blocked by tetrodotoxin and picrotoxin,
      indicating that glucose was acting indirectly to cause the release of GABA.
      Decreasing the glucose concentration of the perfusing solution by one-half
      produced an inward current of 36 +/- 5 pA (n = 7). 4. Stimulation of the NTS
      evoked inhibitory postsynaptic currents (IPSCs) in DMV neurones. The amplitude of
      the evoked IPSCs was positively correlated with glucose concentration. Perfusion
      with the ATP-sensitive K(+) (K(ATP)) channel opener diazoxide mimicked the effect
      of reduced glucose, while perfusion with the K(ATP) channel blocker glibenclamide
      mimicked the effects of increased glucose. 5. Our data indicate that glucose had
      no direct excitatory effect on DMV neurones, but DMV neurones appear to be
      affected by an action of glucose on cell bodies of mNTS neurones via effects on
      an ATP-sensitive potassium channel.

PMID- 11579165
TI  - Acidosis or inorganic phosphate enhances the length dependence of tension in rat
      skinned cardiac muscle.
AB  - 1. We investigated the effect of acidosis on the sarcomere length (SL) dependence
      of tension generation, in comparison with the effect of inorganic phosphate
      (P(i)), in rat skinned ventricular trabeculae. The shift of the mid-point of the
      pCa-tension relationship associated with an increase in SL from 1.9 to 2.3 microm
      (DeltapCa(50)) was studied. 2. Decreasing pH from 7.0 to 6.2 lowered maximal and
      submaximal Ca(2+)-activated tension and increased DeltapCa(50) in a pH-dependent
      manner (from 0.21 +/- 0.01 to 0.30 +/- 0.01 pCa units). The addition of P(i) (20
      mM) decreased maximal tension and enhanced the SL dependence, both to a similar
      degree as observed when decreasing pH to 6.2 (DeltapCa(50) increased from 0.20 +/
      0.01 to 0.29 +/- 0.01 pCa units). 3. Further experiments were performed using 6
      % (w/v) Dextran T-500 (molecular weight approximately 500 000) to osmotically
      reduce interfilament lattice spacing (SL, 1.9 microm). Compared with that at pH
      7.0, in the absence of P(i) the increase in the Ca(2+) sensitivity of tension
      induced by osmotic compression was enhanced at pH 6.2 (0.18 +/- 0.01 vs. 0.25 +/-
      0.01 pCa units) or in the presence of 20 mM P(i) (0.17 +/- 0.01 vs. 0.24 +/- 0.01
      pCa units). 4. H(+), as well as P(i), has been reported to decrease the number of
      strongly binding cross-bridges, which reduces the co-operative activation of the
      thin filament and increases the pool of detached cross-bridges available for
      interaction with actin. It is therefore considered that during acidosis, the
      degree of increase in the number of force-generating cross-bridges upon reduction
      of interfilament lattice spacing is enhanced, resulting in greater SL dependence
      of tension generation. 5. Our results suggest that the Frank-Starling mechanism
      may be enhanced when tension development is suppressed due to increased H(+)
      and/or P(i) under conditions of myocardial ischaemia or hypoxia.

PMID- 11579166
TI  - Protective effects of lactic acid on force production in rat skeletal muscle.
AB  - 1. During strenuous exercise lactic acid accumulates producing a reduction in
      muscle pH. In addition, exercise causes a loss of muscle K(+) leading to an
      increased concentration of extracellular K(+) ([K(+)](o)). Individually, reduced
      pH and increased [K(+)](o) have both been suggested to contribute to muscle
      fatigue. 2. To study the combined effect of these changes on muscle function,
      isolated rat soleus muscles were incubated at a [K(+)](o) of 11 mM, which reduced
      tetanic force by 75 %. Subsequent addition of 20 mM lactic acid led, however, to
      an almost complete force recovery. A similar recovery was observed if pH was
      reduced by adding propionic acid or increasing the CO(2) tension. 3. The recovery
      of force was associated with a recovery of muscle excitability as assessed from
      compound action potentials. In contrast, acidification had no effect on the
      membrane potential or the Ca(2+) handling of the muscles. 4. It is concluded that
      acidification counteracts the depressing effects of elevated [K(+)](o) on muscle
      excitability and force. Since intense exercise is associated with increased
      [K(+)](o), this indicates that, in contrast to the often suggested role for
      acidosis as a cause of muscle fatigue, acidosis may protect against fatigue.
      Moreover, it suggests that elevated [K(+)](o) is of less importance for fatigue
      than indicated by previous studies on isolated muscles.

PMID- 11579167
TI  - Apical tuft input efficacy in layer 5 pyramidal cells from rat visual cortex.
AB  - 1. The integration of synaptic inputs to the apical dendrite of layer 5
      neocortical pyramidal cells was studied using compartment model simulations. The
      goal was to characterize the generation of regenerative responses to synaptic
      inputs under two conditions: (a) where there was an absence of background
      synaptic input, and (b) when the entire cell surface was subjected to a uniform
      blanket of synaptic background conductance such that somatic input resistance was
      reduced 5-fold. 2. Dendritic morphology corresponded to a layer 5 thick-trunked
      pyramidal cell from rat primary visual cortex at postnatal day 28 (P28), with
      distribution of dendritic active currents guided by the electrophysiological
      characteristics of the apical trunk reported in this cell type. Response
      characteristics for two dendritic channel distributions were compared, one of
      which supported Ca(2+) spikes in the apical dendrite. 3. In the absence of
      background, synaptic input to the apical tuft was surprisingly effective in
      eliciting somatic firing when compared with input to apical oblique branches.
      This result obtained even when the tuft membrane was the least excitable in the
      dendritic tree. 4. The special efficacy of tuft input arose because its
      electrotonic characteristics favour development of a sustained depolarization
      which charged the apex of the apical trunk to its firing threshold; once
      initiated in the distal trunk, firing propagated inward to the soma. This
      mechanism did not depend upon the presence of depolarizing channels in tuft
      membrane, but did require an excitable apical trunk. 5. Rather than disconnect
      the tuft, background synaptic conductance enhanced the efficacy advantage enjoyed
      by input arriving there. This counterintuitive result arose because background
      reduced the subthreshold spread of voltage, and so diminished the ability of the
      excitation of various individual oblique branches to combine to charge the
      relatively thick adjacent trunk. In contrast, drive from the depolarized tuft is
      exerted at a single critical point, the apex of the distal trunk, and so was
      relatively undiminished by the background. Further, once initiation at the apex
      occurred, background had little effect on inward propagation along the trunk. 6.
      We conclude that synaptic input to the apical tuft of layer 5 cells may be
      unexpectedly effective in triggering cell firing in vivo. The advantage in
      efficacy was not dependent upon the characteristics of tuft membrane
      excitability, but rather stemmed from the geometry of the tuft and its junction
      with the distal apical trunk. The efficacy of tuft input was, however, critically
      dependent upon inward propagation, suggesting that modulation of membrane
      currents which affect propagation in the apical trunk might sensitively control
      the efficacy of tuft input.

PMID- 11579168
TI  - Quantal components of the excitatory postsynaptic currents at a rat central
      auditory synapse.
AB  - 1. Paired whole-cell recordings were made from a glutamatergic giant nerve
      terminal, the calyx of Held, and its postsynaptic target cell in the medial
      nucleus of the trapezoid body (MNTB) in the brainstem slice of juvenile rat.
      Excitatory postsynaptic currents (EPSCs) were evoked by presynaptic action
      potentials triggered by brief (1 ms) depolarizing pulses. 2. In normal artificial
      cerebrospinal fluid (ACSF), EPSCs of several nanoamperes in amplitude were evoked
      at a relatively constant latency with no failure, whereas in low [Ca(2+)](o)-high
      [Mg(2+)](o) solutions, EPSCs fluctuated both in amplitude and latency, and
      stochastic failures of transmitter release were observed in response to
      presynaptic action potentials. 3. After blocking action potentials with
      tetrodotoxin (TTX), direct depolarization of the calyceal preterminal elicited
      asynchronous release of miniature EPSCs (mEPSCs). When the magnitude of
      depolarization was increased, mEPSCs increased in frequency. Being consistent
      with their quantal nature, their mean amplitude remained constant over a wide
      range of frequencies. The amplitude distribution of mEPSCs was slightly skewed
      (skewness = 1.06), with a mean conductance of 0.45 nS and a coefficient of
      variation (c.v.) of 0.43. 4. Single-channel conductance underlying mEPSCs was
      estimated using non-stationary fluctuation analysis. The weighted mean single
      channel conductance was 20.4 pS, suggesting that a single quantum opens 22
      postsynaptic glutamate receptor channels on average. 5. After washing out TTX,
      EPSCs evoked by presynaptic action potentials were tested for quantal analysis
      based upon the mean amplitude of mEPSCs and their variance. In low [Ca(2+)](o)
      high [Mg(2+)](o) solutions, quantal contents estimated from the EPSC/mEPSC ratio,
      rate of failures or c.v. assuming Poisson's statistics, coincided with each
      other. Evoked EPSCs could be fitted by integer multiples of mEPSCs with an
      assumption of incremental variance more adequately than the constant variance
      assumption. 6. It is concluded that the rat central auditory synaptic
      transmission is made in a quantal manner as at the frog neuromuscular junction.

PMID- 11579169
TI  - Temperature has a major influence on cardiac natriuretic peptide in salmon.
AB  - 1. Natriuretic peptides have a major role in fluid and electrolyte homeostasis in
      vertebrates. Ambient temperature has a major influence on physiological processes
      in ectothermic animals. Here we have studied the mechanisms of regulation of a
      natriuretic peptide, sCP (salmon cardiac peptide), in salmon (Salmo salar)
      acclimatised and acclimated to varying temperatures. 2. The circulating and
      cardiac levels of sCP were found to be markedly upregulated in warm-acclimatised
      and warm-acclimated salmon. The release of sCP from isolated in vitro perfused
      salmon ventricle was, however, not increased by acclimation to higher
      temperatures, either in basal conditions or when stimulated by mechanical load.
      3. Concomitant measurements of circulating sCP and the biologically inert N
      terminal fragment of pro-sCP showed that the upregulation of circulating sCP at
      warm ambient temperature results from decreased elimination rather than increased
      secretion of sCP. This is the first direct evidence that changes in the
      elimination of a natriuretic peptide are used for important physiological
      regulation. 4. We found a paradoxical increase in cardiac sCP mRNA levels at cold
      temperatures which coincided with hypertrophy of the heart. sCP gene expression
      may therefore serve as a marker of cardiac hypertrophy in salmon, in analogy to
      that of atrial and brain natriuretic peptide (ANP and BNP, respectively) in
      mammals. 5. These results show that temperature has a major influence on the
      regulation of natriuretic peptide production and clearance in salmon. Salmon CP
      offers a novel model for the study of the endocrine function of the heart.

PMID- 11579171
TI  - Circadian rhythms and sleep have additive effects on respiration in the rat.
AB  - 1. We tested two hypotheses: that respiration and metabolism are subject to
      circadian modulation in wakefulness, non-rapid-eye-movement (NREM) sleep and
      rapid-eye-movement (REM) sleep; and that the effects of sleep on breathing vary
      as a function of time of day. 2. Electroencephalogram (EEG), neck electromyogram
      (EMG) and abdominal body temperature (T(b)) were measured by telemetry in six
      male Sprague-Dawley rats. The EEG and EMG were used to identify sleep-wake
      states. Ventilation (V(I)) and metabolic rate (V(CO2)) were measured by
      plethysmography. Recordings were made over 24 h (12:12 h light:dark) when rats
      were in established states of wakefulness, NREM sleep and REM sleep. 3.
      Statistically significant circadian rhythms were observed in V(I) and V(CO2) in
      each of the wakefulness, NREM sleep and REM sleep states. Amplitudes and phases
      of the circadian rhythms were similar across sleep-wake states. 4. The circadian
      rhythm in V(I) was mediated by a circadian rhythm in respiratory frequency
      (f(R)). Tidal volume (V(T)) was unaffected by time of day in all three sleep-wake
      states. 5. The 24 h mean V(I) was significantly greater during wakefulness (363.5
      +/- 18.5 ml min(-1)) than during NREM sleep (284.8 +/- 11.1 ml min(-1)) and REM
      sleep (276.1 +/- 13.9 ml min(-1)). V(CO2) and V(T) each significantly decreased
      from wakefulness to NREM sleep to REM sleep. f(R) was significantly lower in NREM
      sleep than in wakefulness and REM sleep. 6. These data confirm that ventilation
      and metabolism exhibit circadian rhythms during wakefulness, and NREM and REM
      sleep, and refute the hypothesis that state-related effects on breathing vary as
      a function of time of day. We conclude that the effects of circadian rhythms and
      sleep-wake state on respiration and metabolic rate are additive in the rat.

PMID- 11579170
TI  - Divergent roles of glycolysis and the mitochondrial electron transport chain in
      hypoxic pulmonary vasoconstriction of the rat: identity of the hypoxic sensor.
AB  - 1. The mechanisms responsible for sensing hypoxia and initiating hypoxic
      pulmonary vasoconstriction (HPV) are unclear. We therefore examined the roles of
      the mitochondrial electron transport chain (ETC) and glycolysis in HPV of rat
      small intrapulmonary arteries (IPAs). 2. HPV demonstrated a transient
      constriction (phase 1) superimposed on a sustained constriction (phase 2).
      Inhibition of complex I of the ETC with rotenone (100 nM) or complex III with
      myxothiazol (100 nM) did not cause vasoconstriction in normoxia, but abolished
      both phases of HPV. Rotenone inhibited the hypoxia-induced rise in intracellular
      Ca(2+) ([Ca(2+)](i)). Succinate (5 mM), a substrate for complex II, reversed the
      effects of rotenone but not myxothiazol on HPV, but did not affect the rise in
      NAD(P)H fluorescence induced by hypoxia or rotenone. Inhibition of cytochrome
      oxidase with cyanide (100 microM) potentiated phase 2 constriction. 3. Phase 2 of
      HPV, but not phase 1, was highly correlated with glucose concentration, being
      potentiated by 15 mM but abolished in its absence, or following inhibition of
      glycolysis by iodoacetate or 2-deoxyglucose. Glucose concentration did not affect
      the rise in [Ca(2+)](i) during HPV. 4. Depolarisation-induced constriction was
      unaffected by hypoxia except in the absence of glucose, when it was depressed by
      approximately 50 %. Depolarisation-induced constriction was depressed by rotenone
      during hypoxia by 23 +/- 4 %; cyanide was without effect. 5. Hypoxia increased 2
      deoxy-[(3)H]glucose uptake in endothelium-denuded IPAs by 235 +/- 32 %, and in
      mesenteric arteries by 218 +/- 38 %. 6. We conclude that complex III of the
      mitochondrial ETC acts as the hypoxic sensor in HPV, and initiates the rise in
      smooth muscle [Ca(2+)](i) by a mechanism unrelated to changes in cytosolic redox
      state per se, but more probably by increased production of superoxide.
      Additionally, glucose and glycolysis are essential for development of the
      sustained phase 2 of HPV, and support an endothelium-dependent Ca(2+)
      sensitisation pathway rather than the rise in [Ca(2+)](i).

PMID- 11579172
TI  - Pathogenesis of laryngeal narrowing in patients with multiple system atrophy.
AB  - 1. We do not fully understand the pathogenesis of nocturnal laryngeal stridor in
      patients with multiple system atrophy (MSA). Recent studies suggest that
      inspiratory thyroarytenoid (TA) muscle activation has a role in the development
      of the stridor. 2. The breathing pattern and firing timing of TA muscle
      activation were determined in ten MSA patients, anaesthetized with propofol and
      breathing through the laryngeal mask airway, while the behaviour of the laryngeal
      aperture was being observed endoscopically. 3. Two distinct breathing patterns,
      i.e. no inspiratory flow limitation (no-IFL) and IFL, were identified during the
      measurements. During IFL, significant laryngeal narrowing was observed leading to
      an increase in laryngeal resistance and end-tidal carbon dioxide concentration.
      Development of IFL was significantly associated with the presence of phasic
      inspiratory activation of TA muscle. Application of continuous positive airway
      pressure suppressed the TA muscle activation. 4. The results indicate that
      contraction of laryngeal adductors during inspiration narrows the larynx leading
      to development of inspiratory flow limitation accompanied by stridor in patients
      with MSA under general anaesthesia.

PMID- 11579173
TI  - Respiratory sinus arrhythmia: opposite effects on systolic and mean arterial
      pressure in supine humans.
AB  - 1. Are arterial blood pressure fluctuations buffered or reinforced by respiratory
      sinus arrhythmia (RSA)? There is still considerable debate about this simple
      question. Different results have been obtained, triggering a discussion as to
      whether or not the baroreflexes are responsible for RSA. We suspected that the
      measurements of different aspects of arterial pressure (mean arterial pressure
      (MAP) and systolic pressure (SP)) can explain the conflicting results. 2.
      Simultaneous recordings of beat-to-beat MAP, SP, left cardiac stroke volume (SV,
      pulsed ultrasound Doppler), heart rate (HR) and respiration (RE) were obtained in
      10 healthy young adults during spontaneous respiration. In order to eliminate HR
      variations at respiratory frequency we used propranolol and atropine
      administration in the supine and tilted positions. Respiration-synchronous
      variation in the recorded variables was quantified by spectral analysis of the
      recordings of each of these variables, and the phase relations between them were
      determined by cross-spectral analysis. 3. MAP fluctuations increased after
      removing heart rate variations in both supine and tilted position, whereas SP
      fluctuations decreased in the supine position and increased in the head-up tilted
      position. 4. RSA buffers respiration-synchronous fluctuations in MAP in both
      positions. However, fluctuations in SP were reinforced by RSA in the supine and
      buffered in the tilted position.

PMID- 11579174
TI  - Muscle oxygen uptake and energy turnover during dynamic exercise at different
      contraction frequencies in humans.
AB  - 1. It has been established that pulmonary oxygen uptake is greater during cycle
      exercise in humans at high compared to low contraction frequencies. However, it
      is unclear whether this is due to more work being performed at the high
      frequencies and whether the energy turnover of the working muscles is higher. The
      present study tested the hypothesis that human skeletal muscle oxygen uptake and
      energy turnover are elevated during exercise at high compared to low contraction
      frequency when the total power output is the same. 2. Seven subjects performed
      single-leg dynamic knee-extensor exercise for 10 min at contraction frequencies
      of 60 and 100 r.p.m. where the total power output (comprising the sum of external
      and internal power output) was matched between frequencies (54 +/- 5 vs. 56 +/- 5
      W; mean +/- S.E.M.). Muscle oxygen uptake was determined from measurements of
      thigh blood flow and femoral arterial - venous differences for oxygen content (a
      v O(2) diff). Anaerobic energy turnover was estimated from measurements of
      lactate release and muscle lactate accumulation as well as muscle ATP and
      phosphocreatine (PCr) utilisation based on analysis of muscle biopsies obtained
      before and after each exercise bout. 3. Whilst a-v O(2) diff was the same between
      contraction frequencies during exercise, thigh blood flow was higher (P < 0.05)
      at 100 compared to 60 r.p.m. Thus, muscle V(O2) was higher (P < 0.05) during
      exercise at 100 r.p.m. Muscle V(O2) increased (P < 0.05) by 0.06 +/- 0.03 (12 %)
      and 0.09 +/- 0.03 l min(-1) (14 %) from the third minute to the end of exercise
      at 60 and 100 r.p.m., respectively, but there was no difference between the two
      frequencies. 4. Muscle PCr decreased by 8.1 +/- 1.7 and 9.1 +/- 2.0 mmol (kg wet
      wt)(-1), and muscle lactate increased to 6.8 +/- 2.1 and 9.8 +/- 2.5 mmol (kg wet
      wt)(-1) during exercise at 60 and 100 r.p.m., respectively. The total release of
      lactate during exercise was 48.7 +/- 8.8 and 64.3 +/- 10.6 mmol at 60 and 100
      r.p.m. (not significant, NS). The total anaerobic ATP production was 47 +/- 8 and
      61 +/- 12 mmol kg(-1), respectively (NS). 5. Muscle temperature increased (P <
      0.05) from 35.8 +/- 0.3 to 38.2 +/- 0.2 degrees C at 60 r.p.m. and from 35.9 +/-
      0.3 to 38.4 +/- 0.3 degrees C at 100 r.p.m. Between 1 and 7 min muscle
      temperature was higher (P < 0.05) at 100 compared to 60 r.p.m. 6. The estimated
      mean rate of energy turnover during exercise was higher (P < 0.05) at 100
      compared to 60 r.p.m. (238 +/- 16 vs. 194 +/- 11 J s(-1)). Thus, mechanical
      efficiency was lower (P < 0.05) at 100 r.p.m. (24 +/- 2 %) compared to 60 r.p.m.
      (28 +/- 3 %). Correspondingly, efficiency expressed as work per mol ATP was lower
      (P < 0.05) at 100 than at 60 r.p.m. (22.5 +/- 2.1 vs. 26.5 +/- 2.5 J (mmol ATP)(
      1)). 7. The present study showed that muscle oxygen uptake and energy turnover
      are elevated during dynamic contractions at a frequency of 100 compared with 60
      r.p.m. It was also observed that muscle oxygen uptake increased as exercise
      progressed in a manner that was not solely related to the increase in muscle
      temperature and lactate accumulation.

PMID- 11579175
TI  - Marathon running increases ERK1/2 and p38 MAP kinase signalling to downstream
      targets in human skeletal muscle.
AB  - 1. We tested the hypothesis that long-distance running activates parallel mitogen
      activated protein kinase (MAPK) cascades that involve extracellular signal
      regulated kinase 1 and 2 (ERK1/2) and p38 MAPK and their downstream substrates.
      2. Eleven men completed a 42.2 km marathon (mean race time 4 h 1 min; range 2 h
      56 min to 4 h 33 min). Vastus lateralis muscle biopsies were obtained before and
      after the race. Glycogen content was measured spectrophotometrically. ERK1/2 and
      p38 MAPK phosphorylation was determined by immunoblot analysis using
      phosphospecific antibodies. Activation of the downstream targets of ERK1/2 and
      p38 MAPK, MAPK-activated protein kinase-1 (MAPKAP-K1; also called p90 ribosomal
      S6 kinase, p90rsk), MAPK-activated protein kinase-2 (MAPKAP-K2), mitogen- and
      stress-activated kinase 1 (MSK1) and mitogen- and stress-activated kinase 2
      (MSK2) was determined using immune complex assays. 3. Muscle glycogen content was
      reduced by 40 +/- 6 % after the marathon. ERK1/2 phosphorylation increased 7.8
      fold and p38 MAPK phosphorylation increased 4.4-fold post-exercise. Prolonged
      running did not alter ERK1/2 and p38 MAPK protein expression. The activity of
      p90rsk, a downstream target of ERK1/2, increased 2.8-fold after the marathon. The
      activity of MAPKAPK-K2, a downstream target of p38 MAPK, increased 3.1-fold post
      exercise. MSK1 and MSK2 are downstream of both ERK1/2 and p38 MAPK. MSK1 activity
      increased 2.4-fold post-exercise. MSK2 activity was low, relative to MSK1, with
      little activation post-exercise. 4. In conclusion, prolonged distance running
      activates MAPK signalling cascades in skeletal muscle, including increased
      activity of downstream targets: p90rsk, MAPKAP-K2 and MSK. Activation of these
      downstream targets provides a potential mechanism by which exercise induces gene
      transcription in skeletal muscle.

PMID- 11579176
TI  - Role of the sympathoadrenergic system in adipose tissue metabolism during
      exercise in humans.
AB  - 1. The relative roles of sympathetic nerve activity and circulating
      catecholamines for adipose tissue lipolysis during exercise are not known. 2.
      Seven paraplegic spinal cord injured (SCI, injury level T3-T5) and seven healthy
      control subjects were studied by microdialysis and (133)xenon washout in
      clavicular (Cl) and in umbilical (Um) (sympathetically decentralized in SCI)
      subcutaneous adipose tissue during 1 h of arm cycling exercise at approximately
      60 % of the peak rate of oxygen uptake. 3. During exercise, adipose tissue blood
      flow (ATBF) and interstitial glycerol, lactate and noradrenaline concentrations
      increased significantly in both groups. Plasma catecholamine levels increased
      significantly less with exercise in SCI than in healthy subjects. The exercise
      induced increase in interstitial glycerol concentration in subcutaneous adipose
      tissue was significantly lower in SCI compared with healthy subjects (SCI: 25 +/-
      12 % (Cl), 36 +/- 20 % (Um); healthy: 60 +/- 17 % (Cl), 147 +/- 45 % (Um)) and
      the increase in ATBF was significantly lower (Cl) or similar (Um) in SCI compared
      with healthy subjects (SCI: 1.2 +/- 0.3 ml (100 g)(-1) min(-1) (Cl), 1.0 +/- 0.3
      ml (100 g)(-1) min(-1) (Um); healthy: 2.8 +/- 0.7 ml (100 g)(-1) min(-1) (Cl),
      0.6 +/- 0.3 ml (100 g)(-1) min(-1) (Um)). Accordingly, in both adipose tissues
      lipolysis increased less in SCI compared with healthy subjects, indicating that
      circulating catecholamines are important for the exercise-induced increase in
      subcutaneous adipose tissue lipolysis. In SCI subjects, the exercise-induced
      increase in subcutaneous adipose tissue lipolysis was not lower in decentralized
      than in sympathetically innervated adipose tissue. During exercise the
      interstitial noradrenaline and adrenaline concentrations were lower in SCI
      compared with healthy subjects (P < 0.05) and always lower than arterial plasma
      catecholamine concentrations (P < 0.05). 4. It is concluded that circulating
      catecholamines are important for the exercise-induced increase in subcutaneous
      adipose tissue lipolysis while sympathetic nerve activity is not.

PMID- 11579177
TI  - The effects of increasing exercise intensity on muscle fuel utilisation in
      humans.
AB  - 1. Contemporary stable isotope methodology was applied in combination with muscle
      biopsy sampling to accurately quantify substrate utilisation and study the
      regulation of muscle fuel selection during exercise. 2. Eight cyclists were
      studied at rest and during three consecutive 30 min stages of exercise at
      intensities of 40, 55 and 75 % maximal workload (W(max)). A continuous infusion
      of [U-(13)C]palmitate and [6,6-(2)H(2)]glucose was administered to determine
      plasma free fatty acid (FFA) oxidation and estimate plasma glucose oxidation,
      respectively. Biopsy samples were collected before and after each exercise stage.
      3. Muscle glycogen and plasma glucose oxidation rates increased with every
      increment in exercise intensity. Whole-body fat oxidation increased to 32 +/- 2
      kJ min(-1) at 55 % W(max), but declined at 75 % W(max) (19 +/- 2 kJ min(-1)).
      This decline involved a decrease in the oxidation rate of both plasma FFA and
      triacylglycerol fat sources (sum of intramuscular plus lipoprotein-derived
      triacylglycerol), and was accompanied by increases in muscle pyruvate
      dehydrogenase complex activation and acetylation of the carnitine pool, resulting
      in a decline in muscle free carnitine concentration. 4. We conclude that the most
      likely mechanism for the reduction in fat oxidation during high-intensity
      exercise is a downregulation of carnitine palmitoyltransferase I, either by this
      marked decline in free carnitine availability or by a decrease in intracellular
      pH.

PMID- 11579178
TI  - Unexpected reflex response to transmastoid stimulation in human subjects during
      near-maximal effort.
AB  - 1. In human subjects, a high-voltage electrical pulse between electrodes fixed
      over the mastoid processes activates descending tract axons at the level of the
      cervico-medullary junction to produce motor responses (cevicomedullary evoked
      responses; CMEPs) in the biceps brachii and brachioradialis muscles. 2. During
      isometric maximal voluntary contractions (MVCs) of the elbow flexors, CMEPs in
      the biceps brachii and brachioradialis muscles are sometimes followed by a second
      compound muscle action potential. This response can be observed in single trials
      (amplitude of up to 60 % of the maximal M wave) and follows the CMEP by about 16
      ms in both muscles. The response only occurs during very strong voluntary
      contractions. 3. The second response following transmastoid stimulation appears
      with stimulation intensities that are at the threshold for evoking a CMEP in the
      contracting muscles. The response grows with increasing stimulus intensity, but
      then decreases in amplitude and finally disappears at high stimulation
      intensities. 4. A single stimulus to the brachial plexus during MVCs can also
      elicit a second response (following the M wave) in the biceps brachii and
      brachioradialis muscles. The latency of this response is 3-4 ms longer than that
      of the second response observed following transmastoid stimulation. This
      difference in latency is consistent with a reflex response to stimulation of
      large-diameter afferents. 5. The amplitude of the second response to transmastoid
      stimulation can be reduced by appropriately timed subthreshold transcranial
      magnetic stimuli. This result is consistent with intracortical inhibition of the
      response. 6. We suggest that transmastoid stimulation can elicit a large
      transcortical reflex response in the biceps brachii and brachioradialis muscles.
      The response travels via the motor cortex but is only apparent during near
      maximal voluntary efforts.

PMID- 11579181
TI  - Deciding about resuscitation.

PMID- 11579179
TI  - Group I projections from intrinsic foot muscles to motoneurones of leg and thigh
      muscles in humans.
AB  - 1. Group I projections from intrinsic plantar muscles to motoneurones (MNs) of
      human leg and thigh muscles were investigated. Changes in firing probability of
      single motor units (MUs) in the tibialis anterior (TA), peroneus brevis (Per
      brev), soleus (Sol), gastrocnemius medialis (GM), vastus lateralis (VL),
      semitendinosus (ST) and biceps (Bi) were studied after electrical stimuli applied
      to: (i) the tibial nerve (TN) at ankle level, (ii) the corresponding homonymous
      nerve, and (iii) the skin of the heel, to mimic the TN-induced cutaneous
      sensation. 2. Homonymous facilitation, attributable to monosynaptic Ia
      excitation, was found in all the sampled units. Early heteronymous excitation
      elicited by TN stimulation was found in many MUs. Later effects (3-5 ms central
      delay) were bigger and more frequently observed: excitation in most TA and Per
      brev MUs, and inhibition in most Sol, GM and Bi MUs and in many ST and VL MUs.
      The low threshold (approximately 0.5-0.6 x motor threshold) and the inability of
      a pure cutaneous stimulation to reproduce these effects (except the late
      excitation in TA MUs) indicate that they were due to stimulation of group I
      muscle afferents. 3. The early excitation was accepted to be monosynaptic when
      its central delay differed from that of the homonymous Ia excitation by less than
      0.5 ms. Such a significant TN-induced monosynaptic Ia excitation was found in MUs
      belonging to all leg and thigh motor nuclei tested. Although its mean strength
      was relatively weak, it is argued that these monosynaptic connections might
      affect already depolarized MNs. 4. The late excitation found in TA and Per brev
      MUs is argued to be mediated through interneurones located rostral to MNs. 5. The
      late suppression, found in most Sol, GM and Bi MUs, and in many ST and VL MUs,
      was the dominant effect. It was accompanied by an inhibition of the Sol and
      quadriceps H reflexes at rest, and therefore reflects an inhibition directed to
      MNs. Its long latency is argued to reflect transmission by interneurones located
      rostral to MNs (the inhibitory counterpart of non-monosynaptic excitation). 6.
      The functional implications of these connections are discussed with respect to
      the requirements of the stance phase of human walking and running.

PMID- 11579182
TI  - Ethics and innovation in medicine.

PMID- 11579183
TI  - Mental illness: psychiatry's phlogiston.
AB  - In physics, we use the same laws to explain why airplanes fly, and why they
      crash. In psychiatry, we use one set of laws to explain sane behaviour, which we
      attribute to reasons (choices), and another set of laws to explain insane
      behaviour, which we attribute to causes (diseases). God, man's idea of moral
      perfection, judges human deeds without distinguishing between sane persons
      responsible for their behaviour and insane persons deserving to be excused for
      their evil deeds. It is hubris to pretend that the insanity defence is
      compassionate, just, or scientific. Mental illness is to psychiatry as phlogiston
      was to chemistry. Establishing chemistry as a science of the nature of matter
      required the recognition of the non-existence of phlogiston. Establishing
      psychiatry as a science of the nature of human behaviour requires the recognition
      of the non-existence of mental illness.

PMID- 11579184
TI  - Why sex selection should be legal.
AB  - Reliable medically assisted sex selection which does not involve abortion or
      infanticide has recently become available, and has been used for non-medical
      reasons. This raises questions about the morality of sex selection for non
      medical reasons. But reasonable people continue to disagree about the answers to
      these questions. So another set of questions is about what the law should be on
      medically assisted sex selection for non-medical reasons in the face of
      reasonable disagreement about the morality of sex selection. This paper sketches
      a way of thinking about what the law should be, and concludes, contrary to what
      the law is in many places, that medically assisted sex selection for non-medical
      reasons ought to be legal.

PMID- 11579185
TI  - Professional guidelines on Decisions Relating to Cardiopulmonary Resuscitation:
      introduction.

PMID- 11579186
TI  - Decisions Relating to Cardiopulmonary Resuscitation: a joint statement from the
      British Medical Association, the Resuscitation Council (UK) and the Royal College
      of Nursing.

PMID- 11579190
TI  - Doctors' and nurses' attitudes towards and experiences of voluntary euthanasia:
      survey of members of the Japanese Association of Palliative Medicine.
AB  - OBJECTIVE: To demonstrate Japanese doctors' and nurses' attitudes towards and
      practices of voluntary euthanasia (VE) and to compare their attitudes and
      practices in this regard. DESIGN: Postal survey, conducted between October and
      December 1999, using a self-administered questionnaire. PARTCIPANTS: All doctor
      members and nurse members of the Japanese Association of Palliative Medicine.
      MAIN OUTCOME MEASURE: Doctors' and nurses' attitude towards and practices of VE.
      RESULTS: We received 366 completed questionnaires from 642 doctors surveyed
      (response rate, 58%) and 145 from 217 nurses surveyed (68%). A total of 54% (95%
      confidence interval (CI): 49-59) of the responding doctors and 53% (CI: 45-61) of
      the responding nurses had been asked by patients to hasten death, of whom 5% (CI:
      2-8) of the former and none of the latter had taken active steps to bring about
      death. Although 88% (CI: 83-92) of the doctors and 85% (CI: 77-93) of the nurses
      answered that a patient's request to hasten death can sometimes be rational, only
      33% (CI: 28-38) and 23% (CI: 16-30) respectively regarded VE as ethically right
      and 22% (CI: 18-36) and 15% (CI: 8-20) respectively would practise VE if it were
      legal. Logistic regression model analysis showed that the respondents' profession
      was not a statistically independent factor predicting his or her response to any
      question regarding attitudes towards VE. CONCLUSIONS: A minority of responding
      doctors and nurses thought VE was ethically or legally acceptable. There seems no
      significant difference in attitudes towards VE between the doctors and nurses.
      However, only doctors had practised VE.

PMID- 11579191
TI  - A protocol for consultation of another physician in cases of euthanasia and
      assisted suicide.
AB  - OBJECTIVE: Consultation of another physician is an important method of review of
      the practice of euthanasia. For the project "support and consultation in
      euthanasia in Amsterdam" which is aimed at professionalising consultation, a
      protocol for consultation was developed to support the general practitioners who
      were going to work as consultants and to ensure uniformity. PARTICIPANTS: Ten
      experts (including general practitioners who were experienced in euthanasia and
      consultation, a psychiatrist, a social geriatrician, a professor in health law
      and a public prosecutor) and the general practitioners who were going to use the
      protocol. EVIDENCE: There is limited literature on consultation: discursive
      articles and empirical studies describing the practice of euthanasia. CONSENSUS:
      An initial draft on the basis of the literature was commented on by the experts
      and general practitioners in two rounds. Finally, the protocol was amended after
      it had been used during the training of consultants. CONCLUSIONS: The protocol
      differentiates between steps that are necessary in a consultation and steps that
      are recommended. Guidelines about four important aspects of consultation were
      given: independence, expertise, tasks and judgment of the consultant. In 97% of
      109 consultations in which the protocol was used the consultant considered the
      protocol to be useful to a greater or lesser extent. Although this protocol was
      developed locally, it also employs universal principles. Therefore it can be of
      use in the development of consultation elsewhere.

PMID- 11579192
TI  - Are antipsychotic drugs the right treatment for challenging behaviour in learning
      disability?: The place of a randomised trial.
AB  - People with learning disability sometimes display challenging behaviour. This can
      be managed by use of antipsychotic medication or behavioural therapy or both.
      There is no solid evidence, however, that these therapies are safe and effective.
      A randomised controlled trial of antipsychotic medication has been proposed to
      deliver such evidence. However, this presents difficult issues in the ethics of
      research with learning disabled people. In particular, is a trial the most
      efficient and fairest way to evaluate practice in this area? This paper reviews
      the clinical situation, gives the rationale for the trial, and analyses the
      ethical arguments for and against such a trial.

PMID- 11579193
TI  - A survey of newly appointed consultants' attitudes towards research fraud.
AB  - OBJECTIVE: To determine the prevalence of, and attitudes towards, observed and
      personal research misconduct among newly appointed medical consultants. DESIGN:
      Questionnaire study. SETTING: Mersey region, United Kingdom. PARTICIPANTS:
      Medical consultants appointed between Jan 1995 and Jan 2000 in seven different
      hospital trusts (from lists provided by each hospital's personnel department).
      MAIN OUTCOME MEASURES: Reported observed misconduct, reported past personal
      misconduct and reported possible future misconduct. RESULTS: One hundred and
      ninety-four replies were received (a response rate of 63.6%); 55.7% of
      respondents had observed some form of research misconduct; 5.7% of respondents
      admitted to past personal misconduct; 18% of respondents were either willing to
      commit or unsure about possible future research misconduct. Only 17% of the
      respondents reported having received any training in research ethics.
      Anaesthetists reported a lower incidence of observed research misconduct (33.3%)
      than the rest of the respondents (61.5%) (p<0.05). CONCLUSION: There is a higher
      prevalence of observed and possible future misconduct among newly appointed
      consultants in the UK than in the comparable study of biomedical trainees in
      California. Although there is a need for more extensive studies, this survey
      suggests that there is a real and potential problem of research misconduct in the
      UK.

PMID- 11579194
TI  - Ethical approval for research involving geographically dispersed subjects:
      unsuitability of the UK MREC/LREC system and relevance to uncommon genetic
      disorders.
AB  - OBJECTIVES: To assess the process involved in obtaining ethical approval for a
      single-centre study involving geographically dispersed subjects with an uncommon
      genetic disorder. DESIGN: Observational data of the application process to 53
      local research ethics committees (LRECs) throughout Wales, England and Scotland.
      The Multicentre Research Ethics Committee (MREC) for Wales had already granted
      approval. RESULTS: Application to the 53 LRECs required 24,552 sheets of paper
      and took two months of the researcher's time. The median time taken for approval
      was 39 days with only seven (13%) of committees responding within the recommended
      21 days. In at least nineteen cases (36%) a subcommittee considered the
      application. Thirty-three committees (62%) accepted the proposal without
      amendments but, of the remainder, four (8%) requested changes outside of the
      remit of LRECs. DISCUSSION: Difficulties still exist with the system for
      obtaining ethical approval for studies involving a single centre but with
      patients at multiple sites, as is often required for genetic observational
      research. As such studies differ from true multicentre studies, it may be
      advantageous to develop a separate and specific process of application to ensure
      that resources are not unnecessarily expended in the quest for ethical approval.

PMID- 11579197
TI  - Hospitalised mentally ill patients vote in Israel.

PMID- 11579196
TI  - Changes in attitudes regarding cancer disclosure among medical students at the
      American University of Beirut.

PMID- 11579198
TI  - Jehovah's Witnesses and blood transfusions.

PMID- 11579199
TI  - Molecular and genetic mechanisms of tumorigenesis in multiple endocrine neoplasia
      type-1.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is a rare but informative syndrome for
      endocrine tumorigenesis. Since its isolation, several groups have begun to
      determine the role of menin, the protein product of MEN1, in sporadic endocrine
      tumors as well as tumors of the MEN1 syndrome. Mutations of menin have been
      reported in more than 400 families and tumors, most of which are truncating
      mutations, thus supporting the function of menin as a tumor suppressor. The exact
      function of menin is unknown, but overexpression of menin inhibits proliferation
      of Ras-transformed NIH3T3 cells. Since menin interacts with proteins from both
      the TGF beta and AP-1 signaling pathways, perhaps its tumor suppressor function
      is related to these key cell growth pathways. In this review we will discuss the
      various clinical manifestations of MEN1 syndrome, potential mechanisms of MEN1
      tumorigenesis, and mutations associated with MEN and sporadic endocrine tumors.

PMID- 11579200
TI  - CCAAT/enhancer binding protein alpha assembles essential cooperating factors in
      common subnuclear domains.
AB  - The transcription factor CCAAT/enhancer binding protein alpha (C/EBP alpha) is
      the DNA binding subunit of a multiprotein complex that regulates the pituitary
      specific GH promoter. C/EBP alpha is absent from the GHFT1-5 pituitary progenitor
      cell line in which ectopic C/EBP alpha expression leads to activation of the
      otherwise dormant GH promoter. Transcriptional regulatory complexes are commonly
      envisaged as assembling from components that evenly diffuse throughout the
      nucleoplasm. We show that C/EBP alpha, expressed in GHFT1-5 cells as a fusion
      with color variants of the green fluorescent protein (GFP), concentrated
      specifically at peri-centromeric chromosomal domains. Although we found the CREB
      binding protein (CBP) to activate C/EBP alpha-dependent transcription, CBP was
      absent from the pericentromeric chromatin. C/EBP alpha expression was accompanied
      by the translocation of endogenous and ectopically expressed CBP to
      pericentromeric chromatin. The intranuclear recruitment of CBP required the
      transcriptional activation domains of C/EBP alpha. C/EBP alpha also caused GFP
      tagged TATA binding protein (TBP) to relocate to the Hoechst-stained domains. The
      altered intranuclear distribution of critical coregulatory factors defines
      complexes formed upon C/EBP alpha expression. It also identifies an
      organizational activity, which we label "intranuclear marshalling," that may
      regulate gene expression by determining the cooperative and antagonistic
      interactions available at specific nuclear sites.

PMID- 11579201
TI  - Transactivation via RAR/RXR-Sp1 interaction: characterization of binding between
      Sp1 and GC box motif.
AB  - Modulation of Sp1 activity by nuclear receptors is a novel mechanism by which fat
      soluble hormones regulate gene expression. We previously established that upon
      autoinduction of RARs by RA, RARs/RXRs physically interact with Sp1, potentiate
      Sp1 binding to the GC box motifs, and thus enhance transactivation of the
      urokinase promoter, which lacks a canonical RAR-responsive element/RXR-responsive
      element. Here, we examined whether a similar mechanism might participate in
      transcriptional regulation of other key RA-inducible genes in endothelial cells
      and characterized binding between Sp1 and GC box motifs. Northern blot analyses
      showed that in addition to urokinase, after induction of RARs, RA up-regulates GC
      rich region-dependent mRNA expression of transglutaminase, TGF beta 1, and types
      I and II TGF beta receptors. RA failed to alter the expression of Sp1 at both
      mRNA and protein levels. Reporter and gel shift assays and Western blot analyses
      suggested that either RA-treatment or RAR/RXR-overexpression enhances
      transactivation of these genes through a GC-rich region and strengthens the
      affinity of Sp1 to GC box motifs, accompanying a potential conformational change
      of Sp1 as reflected in its increased immunogenicity. Detailed analyses of the GC
      box motifs within the urokinase and other promoters indicate that interaction
      between RAR/RXR and Sp1 does not occur in the presence of nonfunctional GC box
      motifs containing five tandem purine or pyrimidine bases at the 3'-flanking
      region of hexanucleotide core sequence. These findings provide insight into the
      molecular mechanisms underlying RARE/RXRE-independent transactivation of RA
      inducible gene promoters.

PMID- 11579202
TI  - Cloning and characterization of gonadotropin-inducible ovarian transcription
      factors (GIOT1 and -2) that are novel members of the (Cys)(2)-(His)(2)-type zinc
      finger protein family.
AB  - Gonadotropins are essential for ovarian follicular development and
      differentiation. To identify genes that are rapidly induced by gonadotropin in
      the immature rat ovary, ovarian genes were screened by a subtraction cloning
      procedure. cDNA clones encoding novel members of the (Cys)(2)-(His)(2)-type zinc
      finger protein family GIOT1 and -2 (gonadotropin-inducible transcription factor 1
      and 2), were identified. Two isoforms of GIOT2 (GIOT2 alpha and 2 beta), which
      are probably produced by alternative splicing, also exist. Nucleotide sequence
      analysis revealed that GIOT1, but not GIOT2, contains the kruppel-associated box
      A domain at the NH(2) terminus. RNA analyses revealed that these mRNAs were
      rapidly and temporarily induced by gonadotropins in the rat testis as well as in
      the ovary. In situ hybridization study revealed that expression of GIOT1 was
      induced in theca interna cells in the ovary and Leydig cells in the testis.
      Interestingly, the gene expression of GIOT1 is restricted to the pituitary,
      adrenal, testis, and ovary, while GIOT2 gene is expressed ubiquitously. A
      functional analysis of GIOT1 and -2 by a GAL4-based mammalian one-hybrid system
      revealed that GIOT1, but not GIOT2, is a transcriptional repressor and that the
      kruppel-associated box-A domain of GIOT1 is responsible for the transcriptional
      repressor activity. A GAL4-based yeast two-hybrid system was also used to
      identify proteins that interact with the rat GIOT1. We cloned genes encoding rat
      homologs of human I-mfa domain containing protein and transcriptional
      intermediary factor 1 beta, both of which are transcription-regulatory proteins.
      Interaction of these proteins with GIOT1 was directly demonstrated by GST pull
      down assay. Our data strongly suggest that GIOT1 may function as a novel
      transcriptional repressor by working with rat homologs of human I-mfa domain
      containing protein and transcriptional intermediary factor 1 beta proteins and
      may play a significant role at the transcription level in the folliculogenesis.

PMID- 11579203
TI  - Association of beta-Arrestin 1 with the type 1A angiotensin II receptor involves
      phosphorylation of the receptor carboxyl terminus and correlates with receptor
      internalization.
AB  - Arrestins bind to phosphorylated G protein-coupled receptors and participate in
      receptor desensitization and endocytosis. Although arrestins traffic with
      activated type 1 (AT(1A)) angiotensin II (AngII) receptors, the contribution of
      arrestins to AT(1A) receptor internalization is controversial, and the physical
      association of arrestins with the AT(1A) receptor has not been established. In
      this study, by coimmunoprecipitating AT(1A) receptors and beta-arrestin 1, we
      provide direct evidence for an association between arrestins and the AT(1A)
      receptor that was agonist- and time-dependent and contingent upon the level of
      beta-arrestin 1 expression. Serial truncation of the receptor carboxyl terminus
      resulted in a graded loss of beta-arrestin 1 association, which correlated with
      decreases in receptor phosphorylation. Truncation of the AT(1A) receptor to
      lysine(325) prevented AngII-induced phosphorylation and beta-arrestin 1
      association as well as markedly inhibiting receptor internalization, indicating a
      close correlation between these receptor parameters. AngII-induced association
      was also dramatically reduced in a phosphorylation- and internalization-impaired
      receptor mutant in which four serine and threonine residues in the central
      portion of the AT(1A) receptor carboxyl terminus (Thr(332), Ser(335), Thr(336),
      Ser(338)) were substituted with alanine. In contrast, substitutions in another
      serine/threonine-rich region (Ser(346), Ser(347), Ser(348)) and at three PKC
      phosphorylation sites (Ser(331), Ser(338), Ser(348)) had no effect on AngII
      induced beta-arrestin 1 association or receptor internalization. While AT(1A)
      receptor internalization could be inhibited by a dominant-negative beta-arrestin
      1 mutant (beta arr1(319-418)), treatment with hyperosmotic sucrose to inhibit
      internalization did not abrogate the differences in arrestin association observed
      between the wild-type and mutant receptors, indicating that arrestin binding
      precedes, and is not dependent upon, receptor internalization. Interestingly, a
      substituted analog of AngII, [Sar(1)Ile(4)Ile(8)]-AngII, which promotes robust
      phosphorylation of the receptor but does not activate receptor signaling,
      stimulated strong beta-arrestin 1 association with the full-length AT(1A)
      receptor. These results identify the central portion of the AT(1A) receptor
      carboxyl terminus as the important determinant for beta-arrestin 1 binding and
      internalization and indicate that AT(1A) receptor phosphorylation is crucial for
      beta-arrestin docking.

PMID- 11579204
TI  - Farnesoid X-activated receptor induces apolipoprotein C-II transcription: a
      molecular mechanism linking plasma triglyceride levels to bile acids.
AB  - The farnesoid X-activated receptor (FXR; NR1H4), a member of the nuclear hormone
      receptor superfamily, induces gene expression in response to several bile acids,
      including chenodeoxycholic acid. Here we used suppression subtractive
      hybridization to identify apolipoprotein C-II (apoC-II) as an FXR target gene.
      Retroviral expression of FXR in HepG2 cells results in induction of the mRNA
      encoding apoC-II in response to several FXR ligands. EMSAs demonstrate that
      recombinant FXR and RXR bind to two FXR response elements that are contained
      within two important distal enhancer elements (hepatic control regions) that lie
      11 kb and 22 kb upstream of the transcription start site of the apoC-II gene. A
      luciferase reporter gene containing the hepatic control region or two copies of
      the wild-type FXR response element was activated when FXR-containing cells were
      treated with FXR ligands. In addition, we report that hepatic expression of both
      apoC-II and phospholipid transfer protein mRNAs increases when mice are fed diets
      supplemented with cholic acid, an FXR ligand, and this induction is attenuated in
      FXR null mice. Finally, we observed decreased plasma triglyceride levels in mice
      fed cholic acid- containing diets. These results identify a mechanism whereby FXR
      and its ligands lower plasma triglyceride levels. These findings may have
      important implications in the clinical management of hyperlipidemias.

PMID- 11579205
TI  - Potentiation of glucose uptake in 3T3-L1 adipocytes by PPAR gamma agonists is
      maintained in cells expressing a PPAR gamma dominant-negative mutant: evidence
      for selectivity in the downstream responses to PPAR gamma activation.
AB  - Pharmacological agonists for the nuclear receptor PPAR gamma enhance glucose
      disposal in a variety of insulin-resistant states in humans and animals. The
      precise mechanisms whereby activation of PPAR gamma leads to increased glucose
      uptake in metabolically active cells remain to be determined. Notably, certain
      novel, synthetic PPAR gamma ligands appear to antagonize thiazolidinedione
      induced adipogenesis yet stimulate cellular glucose uptake. We have explored the
      molecular mechanisms underlying the enhancement of glucose uptake produced by
      PPAR gamma agonists in 3T3-L1 adipocytes. Rosiglitazone treatment for 48 h
      significantly increased basal and insulin-stimulated glucose uptake and markedly
      increased the cellular expression of GLUT1 but not GLUT4. Rosiglitazone increased
      plasma membrane levels of GLUT1, but not GLUT4, both basally and after insulin
      stimulation. Surprisingly, adenoviral expression of a dominant-negative mutant
      PPAR gamma, which was demonstrated to strongly inhibit adipogenesis, completely
      failed to inhibit rosiglitazone-stimulated glucose uptake. Similar findings were
      obtained with the non-thiazolidinedione PPAR gamma agonists, GW1929 and GW7845.
      The insensitivity of PPAR gamma agonist-stimulated glucose uptake to expression
      of a dominant-negative mutant, compared with the latter's marked inhibitory
      effects on preadipocyte differentiation, suggests that, as is the case for other
      nuclear receptors, the precise molecular mechanisms linking PPAR gamma activation
      to downstream events may differ depending on the nature of the biological
      response. The growing evidence that the effects of PPAR gamma on adipogenesis and
      glucose uptake can be dissociated may have important implications for the
      development of improved antidiabetic drug treatments.

PMID- 11579206
TI  - Targeted disruption of the pituitary adenylate cyclase-activating polypeptide
      gene results in early postnatal death associated with dysfunction of lipid and
      carbohydrate metabolism.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a hormone belonging
      to the glucagon superfamily of hormones. These hormones are known to play
      important roles in metabolism and growth. PACAP is a neuropeptide that causes
      accumulation of cAMP in a number of tissues and affects the secretion of other
      hormones, vasodilation, neural and immune functions, as well as the cell cycle.
      To determine whether PACAP is essential for survival and to evaluate its
      function(s), we have generated mice lacking the PACAP gene via homologous
      recombination. We found that most PACAP null mice died in the second postnatal
      week in a wasted state with microvesicular fat accumulation in liver, skeletal
      muscle, and heart. Gas chromatography-mass spectrometry showed that fatty acid
      beta-oxidation in liver mitochondria of PACAP(-/-) mice was not blocked based on
      the distribution of 3-hydroxy-fatty acids (C6-16) in the plasma. Instead,
      increased metabolic flux through the beta-oxidation pathway was suggested by the
      presence of ketosis. Also, serum triglycerides and cholesterol were significantly
      higher (2- to 3-fold) in PACAP null mice than littermates. In the fed state, both
      serum insulin and blood glucose were normal in 5-d-old null mice compared with
      their littermates. In contrast, fasted PACAP null pups had a significant increase
      in insulin, but a decrease in blood glucose compared with littermates. Glycogen
      in the liver was reduced. These results suggest PACAP is a critical hormonal
      regulator of lipid and carbohydrate metabolism.

PMID- 11579207
TI  - Conditional deletion of brain-derived neurotrophic factor in the postnatal brain
      leads to obesity and hyperactivity.
AB  - Brain-derived neurotrophic factor has been associated previously with the
      regulation of food intake. To help elucidate the role of this neurotrophin in
      weight regulation, we have generated conditional mutants in which brain-derived
      neurotrophic factor has been eliminated from the brain after birth through the
      use of the cre-loxP recombination system. Brain-derived neurotrophic factor
      conditional mutants were hyperactive after exposure to stressors and had higher
      levels of anxiety when evaluated in the light/dark exploration test. They also
      had mature onset obesity characterized by a dramatic 80-150% increase in body
      weight, increased linear growth, and elevated serum levels of leptin, insulin,
      glucose, and cholesterol. In addition, the mutants had an abnormal starvation
      response and elevated basal levels of POMC, an anorexigenic factor and the
      precursor for alpha-MSH. Our results demonstrate that brain derived neurotrophic
      factor has an essential maintenance function in the regulation of anxiety-related
      behavior and in food intake through central mediators in both the basal and
      fasted state.

PMID- 11579208
TI  - Regulation of insulin gene transcription by a Ca(2+)-responsive pathway involving
      calcineurin and nuclear factor of activated T cells.
AB  - Immunosuppressants such as FK506 (tacrolimus), the primary cellular target of
      which is calcineurin, decrease beta-cell insulin content and preproinsulin mRNA
      expression. This study offers an explanation for this effect by establishing that
      calcineurin is an important regulator of insulin gene expression through the
      activation of a transcription factor, nuclear factor of activated T cells. Three
      putative nuclear factor of activated T cells binding sites were located within
      the proximal region of the rat insulin I gene promoter (-410 to +1 bp).
      Expression of nuclear factor of activated T cells in both clonal (INS-1) and
      primary (islet) beta-cells was confirmed by immunoblot and immunocytochemical
      analyses. Moreover, nuclear factor of activated T cells DNA-binding activity was
      detected in INS-1 and islet nuclear extracts by EMSAs. Activation of the insulin
      gene promoter by glucose or elevated extracellular K(+) (to depolarize the beta
      cell) was totally prevented by FK506 (5-10 microM). K(+)-induced promoter
      activation was suppressed (>65%) by a 2-bp mutation of a single nuclear factor of
      activated T cells binding site in -410 rInsI. Both stimulants also activated a
      minimal promoter-reporter construct containing tandem nuclear factor of activated
      T cells consensus sequences. The effects of FK506 on K(+)-induced nuclear factor
      of activated T cells reporter or insulin gene promoter activity were not mimicked
      by rapamycin, indicating specificity toward calcineurin. These findings suggest
      that the activation of calcineurin by beta-cell secretagogues that elevate
      cytosolic Ca(2+) plays a fundamental role in maintenance of insulin gene
      expression via the activation of nuclear factor of activated T cells.

PMID- 11579209
TI  - Phosphorylation of PTP1B at Ser(50) by Akt impairs its ability to dephosphorylate
      the insulin receptor.
AB  - PTP1B is a protein tyrosine phosphatase that negatively regulates insulin
      sensitivity by dephosphorylating the insulin receptor. Akt is a ser/thr kinase
      effector of insulin signaling that phosphorylates substrates at the consensus
      motif RXRXXS/T. Interestingly, PTP1B contains this motif (RYRDVS(50)), and wild
      type PTP1B (but not mutants with substitutions for Ser(50)) was significantly
      phosphorylated by Akt in vitro. To determine whether PTP1B is a substrate for Akt
      in intact cells, NIH-3T3(IR) cells transfected with either wild-type PTP1B or
      PTP1B-S50A were labeled with [(32)P]-orthophosphate. Insulin stimulation caused a
      significant increase in phosphorylation of wild-type PTP1B that could be blocked
      by pretreatment of cells with wortmannin or cotransfection of a dominant
      inhibitory Akt mutant. Similar results were observed with endogenous PTP1B in
      untransfected HepG2 cells. Cotransfection of constitutively active Akt caused
      robust phosphorylation of wild-type PTP1B both in the absence and presence of
      insulin. By contrast, PTP1B-S50A did not undergo phosphorylation in response to
      insulin. We tested the functional significance of phosphorylation at Ser(50) by
      evaluating insulin receptor autophosphorylation in transfected Cos-7 cells.
      Insulin treatment caused robust receptor autophosphorylation that could be
      substantially reduced by coexpression of wild-type PTP1B. Similar results were
      obtained with coexpression of PTP1B-S50A. However, under the same conditions,
      PTP1B-S50D had an impaired ability to dephosphorylate the insulin receptor.
      Moreover, cotransfection of constitutively active Akt significantly inhibited the
      ability of wild-type PTP1B, but not PTP1B-S50A, to dephosphorylate the insulin
      receptor. We conclude that PTP1B is a novel substrate for Akt and that
      phosphorylation of PTP1B by Akt at Ser(50) may negatively modulate its
      phosphatase activity creating a positive feedback mechanism for insulin
      signaling.

PMID- 11579210
TI  - Glucocorticoid suppression of IGF I transcription in osteoblasts.
AB  - Glucocorticoids have profound effects on bone formation, decreasing IGF I
      transcription in osteoblasts, but the mechanisms involved are poorly understood.
      We previously showed that the bp +34 to +192 region of the rat IGF I exon 1
      promoter was responsible for repression of IGF I transcription by cortisol in
      cultures of osteoblasts from fetal rat calvariae (Ob cells). Here, site-directed
      mutagenesis was used to show that a binding site for members of the CAAT/enhancer
      binding protein family of transcription factors, within the +132 to +158 region
      of the promoter, mediates this glucocorticoid effect. EMSAs demonstrated that
      cortisol increased binding of osteoblast nuclear proteins to the +132 to +158
      region of the IGF I promoter. Supershift assays showed that CAAT/enhancer binding
      protein alpha, beta, and delta interact with this sequence, and binding of
      CAAT/enhancer binding protein delta, in particular, was increased in the presence
      of cortisol. Northern blot analysis showed that CAAT/enhancer binding protein
      delta and beta transcripts were increased by cortisol in Ob cells. Further,
      cortisol increased the transcription of these genes and increased the stability
      of CAAT/enhancer binding protein delta mRNA. In conclusion, cortisol represses
      IGF I transcription in osteoblasts, and CAAT/enhancer binding proteins appear to
      play a role in this effect.

PMID- 11579211
TI  - A G577R mutation in the human AR P box results in selective decreases in DNA
      binding and in partial androgen insensitivity syndrome.
AB  - We have characterized a novel mutation of the human AR, G577R, associated with
      partial androgen insensitivity syndrome. G577 is the first amino acid of the P
      box, a region crucial for the selectivity of receptor/DNA interaction. Although
      the equivalent amino acid in the GR (also Gly) is not involved in DNA
      interaction, the residue at the same position in the ER (Glu) interacts with the
      two central base pairs in the PuGGTCA motif. Using a panel of 16 palindromic
      probes that differ in these base pairs (PuGNNCA) in gel shift experiments with
      either the AR DNA-binding domain or the full length receptor, we observed that
      the G577R mutation does not induce binding to probes that are not recognized by
      the wild-type AR. However, binding to the four PuGNACA elements recognized by the
      wild-type AR was affected to different degrees, resulting in an altered
      selectivity of DNA response element recognition. In particular, AR-G577R did not
      interact with PuGGACA palindromes. Modeling of the complex between mutant AR and
      PuGNACA motifs indicates that the destabilizing effect of the mutation is
      attributable to a steric clash between the C beta of Arg at position 1 of the P
      box and the methyl group of the second thymine residue in the TGTTCPy arm of the
      palindrome. In addition, the Arg side chain can interact with G or T at the next
      position (PuGCACA and PuGAACA elements, respectively). The presence of C is not
      favorable, however, because of incompatible charges, abrogating binding to the
      PuGGACA element. Transactivation of several natural or synthetic promoters
      containing PuGGACA motifs was drastically reduced by the G577R mutation. These
      data suggest that androgen target genes may be differentially affected by the
      G577R mutation, the first natural mutation characterized that alters the
      selectivity of the AR/DNA interaction. This type of mutation may thus contribute
      to the diversity of phenotypes associated with partial androgen insensitivity
      syndrome.

PMID- 11579212
TI  - New androgen response elements in the murine pem promoter mediate selective
      transactivation.
AB  - The Pem homeobox transcription factor is expressed under androgen control in the
      testis and epididymis. It is also transcribed in the ovary, muscle, and placenta.
      The mouse Pem gene promoter was cloned and sequenced. It was analyzed in
      transactivation tests using CV-1 and PC-3 cells expressing the AR and found to be
      strongly stimulated by androgens. EMSAs and mutational analysis of the Pem
      promoter allowed the identification of two functional androgen response elements
      named ARE-1 and ARE-2. They both differed from the consensus semipalindromic
      steroid response element and exhibited characteristics of direct repeats of the
      TGTTCT half-site. Unlike the steroid response element, both Pem androgen response
      elements were selectively responsive to androgen stimulation. Specific mutations
      in the left half-site of Pem ARE-1 and ARE-2, but not of the steroid response
      element, were still compatible with AR binding in the EMSA. In addition, Pem ARE
      1, but not ARE-2 or the steroid response element, showed some flexibility with
      regard to spacing between half-sites. These results strongly suggest that the AR
      interacts differently with direct repeats than with inverted repeats, potentially
      leading to cis element-driven selective properties. Thus, the existence of
      several classes of DNA response elements might be an essential feature of
      differential androgen regulation.

PMID- 11579213
TI  - Androgens stimulate lipogenic gene expression in prostate cancer cells by
      activation of the sterol regulatory element-binding protein cleavage activating
      protein/sterol regulatory element-binding protein pathway.
AB  - Using two independent prostate cancer cell lines (LNCaP and MDA-PCa-2a), we
      demonstrate that coordinated stimulation of lipogenic gene expression by
      androgens is a common phenomenon in androgen-responsive prostate tumor lines and
      involves activation of the sterol regulatory element-binding protein (SREBP)
      pathway. We show 1) that in both cell lines, androgens stimulate the expression
      of fatty acid synthase and hydroxymethylglutaryl-coenzyme A synthase, two key
      lipogenic genes representative for the fatty acid and the cholesterol synthesis
      pathway, respectively; 2) that treatment with androgens results in increased
      nuclear levels of active SREBP; 3) that the effects of androgens on promoter
      reporter constructs derived from both lipogenic genes (fatty acid synthase and
      hydroxymethylglutaryl-coenzyme A synthase) depend on the presence of intact SREBP
      binding sites; and 4) that cotransfection with dominant-negative forms of SREBPs
      abolishes the effects of androgens. Related to the mechanism underlying androgen
      activation of the SREBP pathway, we show that in addition to minor effects on
      SREBP precursor levels, androgens induce a major increase in the expression of
      sterol regulatory element-binding protein cleavage-activating protein (SCAP), an
      escort protein that transports SREBPs from their site of synthesis in the
      endoplasmic reticulum to their site of proteolytical activation in the Golgi.
      Both time course studies and overexpression experiments showing that increasing
      levels of SCAP enhance the production of mature SREBP and stimulate lipogenic
      gene expression support the contention that SCAP plays a pivotal role in the
      lipogenic effects of androgens in tumor cells.

PMID- 11579214
TI  - Binding of the low density lipoprotein receptor-associated protein (RAP) to
      thyroglobulin (Tg): putative role of RAP in the Tg secretory pathway.
AB  - The 39-44 kDa protein known as the receptor-associated protein binds to members
      of the low density lipoprotein receptor family and is found within cells that
      express these receptors. The receptor-associated protein has been shown to
      prevent premature binding of ligands to the receptors in the endoplasmic
      reticulum and to promote proper folding and transport of the receptors in the
      secretory pathway. In the thyroid, megalin (a low-density lipoprotein receptor
      family member) serves as an endocytic receptor for thyroglobulin. Here we present
      evidence that the receptor-associated protein can bind to thyroglobulin, which
      suggests a novel function of the receptor-associated protein, namely binding of
      certain megalin ligands possibly during the biosynthetic pathway. In solid-phase
      assays thyroglobulin was shown to bind to the receptor-associated protein with
      moderately high affinity (mean between K(d) and K(i) = 39.8 nM), in a calcium
      dependent and saturable manner. The receptor-associated protein also bound to a
      native carboxyl-terminal 230-kDa thyroglobulin polypeptide, which markedly
      reduced binding of intact thyroglobulin to the receptor associated protein,
      indicating that the receptor-associated protein binding sites of thyroglobulin
      are located in the carboxyl-terminal portion of the molecule. In addition to
      thyroglobulin, the receptor-associated protein specifically bound to another
      megalin ligand, namely lipoprotein lipase. Because lipoprotein lipase markedly
      reduced receptor-associated protein binding to thyroglobulin, we concluded that
      the receptor-associated protein uses the same binding site/s to bind to
      thyroglobulin and lipoprotein lipase. Evidence of thyroglobulin binding to the
      receptor-associated protein was also obtained in vivo and in cultured thyroid
      cells. Thus, anti-receptor-associated protein antibodies precipitated intact
      thyroglobulin from extracts prepared from rat thyroids and cultured thyroid cells
      (FRTL-5 cells). Chase experiments after inhibition of protein synthesis in FRTL-5
      cells showed that thyroglobulin interacts with the receptor-associated protein
      shortly after the beginning of thyroglobulin biosynthesis.

PMID- 11579217
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 11579215
TI  - The activation of the phosphotyrosine phosphatase eta (r-PTP eta) is responsible
      for the somatostatin inhibition of PC Cl3 thyroid cell proliferation.
AB  - The aim of this study was the characterization of the intracellular effectors of
      the antiproliferative activity of somatostatin in PC Cl3 thyroid cells.
      Somatostatin inhibited PC Cl3 cell proliferation through the activation of a
      membrane phosphotyrosine phosphatase. Conversely, PC Cl3 cells stably expressing
      the v-mos oncogene (PC mos) were completely insensitive to the somatostatin
      antiproliferative effects since somatostatin was unable to stimulate a
      phosphotyrosine phosphatase activity. In PC mos cells basal phosphotyrosine
      phosphatase activity was also reduced, suggesting that the expression of a
      specific phosphotyrosine phosphatase was impaired in these transformed cells. We
      suggested that this phosphotyrosine phosphatase could be r-PTP eta whose
      expression was abolished in the PC mos cells. To directly prove the involvement
      of r-PTP eta in somatostatin's effect, we stably transfected this phosphatase in
      PC mos cells. This new cell line (PC mos/PTP eta) recovered somatostatin's
      ability to inhibit cell proliferation, showing dose-dependence and time course
      similar to those observed in PC Cl3 cells. Conversely, the transfection of a
      catalytically inactive mutant of r-PTP eta did not restore the antiproliferative
      effects of somatostatin. PC mos/PTP eta cells showed a high basal phosphotyrosine
      phosphatase activity which, similarly to PC Cl3 cells, was further increased
      after somatostatin treatment. The specificity of the role of r-PTP eta in
      somatostatin receptor signal transduction was demonstrated by measuring its
      specific activity after somatostatin treatment in an immunocomplex assay.
      Somatostatin highly increased r-PTP eta activity in PCCl3 and PC mos/PTP eta
      (+300%, P < 0.01) but not in PCmos cells. Conversely, no differences in
      somatostatin-stimulated SHP-2 activity, (approximately +50%, P < 0.05), were
      observed among all the cell lines. The activation of r-PTP eta by somatostatin
      caused, acting downstream of MAPK kinase, an inhibition of insulin-induced ERK1/2
      activation with the subsequent blockade of the phosphorylation, ubiquitination,
      and proteasome degradation of the cyclin-dependent kinase inhibitor p27(kip1).
      Ultimately, high levels of p27(kip1) lead to cell proliferation arrest. In
      conclusion, somatostatin inhibition of PC Cl3 cell proliferation requires the
      activation of r-PTP eta which, through the inhibition of MAPK activity, causes
      the stabilization of the cell cycle inhibitor p27(kip1).

PMID- 11579218
TI  - Cunning simplicity of protein folding landscapes.
AB  - Funnel-like landscapes are widely used to visualize protein folding. It might
      seem that any funnel-like energy landscape helps to avoid the 'Levinthal
      paradox', i.e. to avoid sampling the impossibly large number of conformations for
      a folding protein. This cunning suggestion, reinforced by beautiful drawings of
      the energy funnels, stimulated some simple models of protein folding; one of them
      [D.J. Bicout and A. Szabo (2000) Protein Sci., 9, 452-465] is especially
      straightforward and instructive. A thorough analysis of this strict funnel model
      (which does not consider a nucleation of phase separation in the course of
      folding) shows that it cannot provide a simultaneous explanation for both major
      features observed for protein folding: (i) folding within non-astronomical time,
      and (ii) co-existence of the native and the unfolded states during the folding
      process. On the contrary, the nucleation mechanism of protein folding can account
      for both these major features simultaneously.

PMID- 11579219
TI  - A new scale for side-chain contribution to protein stability based on the
      empirical stability analysis of mutant proteins.
AB  - The hydrophobicity scales for amino acid side chains based on the transfer Gibbs
      energy (DeltaG(trans)) of amino acids from non-aqueous phases to water have been
      widely used to estimate the contribution of buried side chains to the
      conformational stability of proteins. In this paper, we propose a new scale for
      the side-chain contribution to protein stability, which is derived from data on
      protein denaturation experiments using systematic and comprehensive mutant
      proteins. In the experiments, the contribution of some physical properties were
      quantitatively determined as parameters in a unique equation representing the
      stability change (DeltaDeltaG) of mutant proteins as a function of the structural
      changes due to the mutations. These parameters are able conveniently to provide a
      scale for the side-chain contribution to protein stability. This new scale also
      has the advantage over the previously reported hydrophobicity scales of residues
      with the contributions of hydrogen bonds or secondary structural propensity. It
      may find practical application in algorithms for the prediction of protein
      structures.

PMID- 11579220
TI  - Design of the linkers which effectively separate domains of a bifunctional fusion
      protein.
AB  - With the aim of separating the domains of a bifunctional fusion protein, the
      ability of several lengths of helix-forming peptides to separate two weakly
      interacting beta-can domains was compared with that of flexible linkers or of a
      three alpha-helices bundle domain. We introduced helix-forming peptide linkers
      A(EAAAK)nA (n = 2-5) between two green fluorescent protein variants, EBFP and
      EGFP, and investigated their spectral properties. The fluorescence resonance
      energy transfer from EBFP to EGFP decreased as the length of the linkers
      increased. The circular dichroism spectra analysis suggested that the linkers
      form an alpha-helix and the alpha-helical contents increased as the length of the
      linkers increased. The results clearly suggested the ability of the helical
      linkers to control the distance and reduce the interference between the domains.
      This 'linker engineering' may open a way to the rational design of linkers which
      maximize the multiple functions of fusion proteins or de novo multi-domain
      proteins.

PMID- 11579221
TI  - Naturally occurring circular permutations in proteins.
AB  - A pair of proteins is defined to be related by a circular permutation if the N
      terminal region of one protein has significant sequence similarity to the C
      terminal of the other and vice versa. To detect pairs of proteins that might be
      related by circular permutation, we implemented a procedure based on a
      combination of a fast screening algorithm that we had designed and manual
      verification of candidate pairs. The screening algorithm is a variation of a
      dynamic programming string matching algorithm, in which one of the sequences is
      doubled. This algorithm, although not guaranteed to identify all cases of
      circular permutation, is a good first indicator of protein pairs related by
      permutation events. The candidate pairs were further validated first by
      application of an exhaustive string matching algorithm and then by manual
      inspection using the dotplot visual tool. Screening the whole Swissprot database,
      a total of 25 independent protein pairs were identified. These cases are
      presented here, divided into three categories depending on the level of
      functional similarity of the related proteins. To validate our approach and to
      confirm further the small number of circularly permuted protein pairs, a
      systematic search for cases of circular permutation was carried out in the Pfam
      database of protein domains. Even with this more inclusive definition of a
      circular permutation, only seven additional candidates were found. None of these
      fitted our original definition of circular permutations. The small number of
      cases of circular permutation suggests that there is no mechanism of local
      genetic manipulation that can induce circular permutations; most examples
      observed seem to result from fusion of functional units.

PMID- 11579222
TI  - Stabilization of local structures by pi-CH and aromatic-backbone amide
      interactions involving prolyl and aromatic residues.
AB  - Weakly polar interactions between the side-chain aromatic rings and hydrogens of
      backbone amides (Ar-HN) and CHn of aliphatic groups (pi-CH) are known to form
      local structures and to stabilize secondary structure in peptides and proteins.
      To investigate the existence of these interactions and to explore their possible
      role in constraining the structures of Pro-Xaa and Xaa-Pro fragments in proteins,
      a database search was performed in a non-redundant set of proteins from the
      Brookheaven Protein Data Bank for pi-CH and Ar-HN interactions in Pro-Xaa and Xaa
      Pro fragments (where Xaa is either Phe, Tyr or Trp). In Xaa-Pro fragments, the
      percentage of pi-CH interactions and Ar-HN interactions, respectively, was 20.6
      and 3.2%, in Pro-Xaa fragments 26.8, 8.6 and 4.0% of the Pro-Xaa fragments
      contained both interactions, while no Xaa-Pro fragments had both. The protein
      fragments containing Ar-HN and/or pi-CH interactions were clustered on the basis
      of similarity of selected torsion angles. The clustering resulted in well defined
      clusters. Thus, pi-CH and Ar(i)-HN(i) interactions were able to constrain
      individual conformations of the Pro-Xaa and Xaa-Pro fragments. These local
      structures were found to be independent of the secondary structure of the
      polypeptide chains in which the fragments were found.

PMID- 11579223
TI  - Evaluation of a novel method for the identification of coevolving protein
      residues.
AB  - A novel method for the identification of correlated pairs in aligned homologous
      protein sequences is presented and evaluated against a model of simulated protein
      evolution incorporating covariation. Our method is shown to be capable of
      identifying all coevolutionary pairs of sites, with minimal interference by
      background correlations, in aligned sequence sets containing approximately 60
      sequences with a tree depth of at least 30 accepted point mutations. This result
      is expected even in the presence of a large degree of neutral and non-correlated
      evolution. It is postulated that, since naturally occurring protein families may
      be subject to stronger selection pressures and a lesser degree of neutral
      evolution, this method of covariation analysis may be generally more robust than
      the model would indicate.

PMID- 11579224
TI  - Knowledge-based potential defined for a rotamer library to design protein
      sequences.
AB  - A knowledge-based potential for a rotamer library was developed to design protein
      sequences. Protein side-chain conformations are represented by 56 templates. Each
      of their fitness to a given structural site-environment is evaluated by a
      combined function of the three knowledge-based terms, i.e. two-body side-chain
      packing, one-body hydration and local conformation. The number of matches between
      the native sequence and the structural site-environment in the database and that
      of the virtually settled mismatches, counted in advance, were transformed into
      the energy scores. In the best-14 test (assessment for the reproduction ability
      of the native rotamer on its structural site within a quarter of 56 fitness rank
      positions), the structural stability analysis on mutants of human and T4
      lysozymes and the inverse-folding search by a structure profile against the
      sequence database, this function performs better than the function deduced with
      the conventional normalization and our previously developed function. Targeting
      various structural motifs, de novo sequence design was conducted with the
      function. The sequences thus obtained exhibit reasonable molecular masses and
      hydrophobic/hydrophilic patterns similar to the native sequences of the target
      and act as if they were the homologs to the target proteins in BLASTP search.
      This significant improvement is discussed in terms of the reference state for
      normalization and the crucial role of short-range repulsion to prohibit residue
      bumps.

PMID- 11579225
TI  - Homology modelling of the ligand-binding domain of glucocorticoid receptor:
      binding site interactions with cortisol and corticosterone.
AB  - Glucocorticoids are involved in the growth, development and homeostasis of a
      number of tissues. The physiological effects of this class of lipophilic steroids
      are mediated by ligand-inducible nuclear transcription factor, the glucocorticoid
      receptor/mineralocorticoid receptor, a member of the steroid/nuclear receptor
      superfamily. The glucocorticoid receptor interacts specifically with
      glucocorticoids, whereas the mineralocorticoid receptor interacts with both
      glucocorticoids and mineralocorticoids. The molecular structure of progesterone
      complexed to its receptor obtained from X-ray crystal structure analysis is used
      to build up a homology model of mouse glucocorticoid receptor ligand-binding
      domain (mGR LBD). The secondary structure of mGR LBD contains 11 helices, nine
      turns and four sheets. The mGR LBD contains a long helix, H9, with 30 residues,
      and exhibits slight deformation when the receptor protein binds with its cognate
      ligands. The mGR LBD has a 12-residue C-terminal extension (residues 772-783)
      that is essential for hormone binding. This extension is tightly fixed in
      position by an antiparallel beta-sheet interaction between amino acids 680-682
      (S3) and 775-777 (S4). The three-dimensional model reveals two polar sites
      located at the extremities of the elongated hydrophobic ligand-binding pocket.
      Cortisol and corticosterone are docked to this ligand-binding pocket. The
      difference accessible surface area study revealed the steroid-binding region of
      mGR LBD.

PMID- 11579226
TI  - Design, high-level expression, purification and characterization of soluble
      fragments of the hepatitis C virus NS3 RNA helicase suitable for NMR-based drug
      discovery methods and mechanistic studies.
AB  - RNA helicases represent a family of enzymes that unwind double-stranded (ds) RNA
      in a nucleoside triphosphate (NTP)-dependent fashion and which are required in
      all aspects of cellular RNA metabolism and processing. The hepatitis C virus
      (HCV) non-structural 3 (NS3) protein possesses a serine protease activity in the
      N-terminal one-third, whereas RNA-stimulated NTPase and helicase activities
      reside in the C-terminal portion of the 631 amino acid residue bifunctional
      enzyme. The HCV NS3 RNA helicase is of key importance in the life cycle of HCV,
      which makes it a target for the development of therapeutics. However, neither the
      precise mechanism nor the substrate structure has been defined for this enzyme.
      For nuclear magnetic resonance (NMR)-based drug discovery methods and for
      mechanistic studies we engineered, prepared and characterized various truncated
      constructs of the 451-residue HCV NS3 RNA helicase. Our goal was to produce
      smaller fragments of the enzyme, which would be amenable to solution NMR
      techniques while retaining their native NTP and/or nucleic acid binding sites.
      Solution conditions were optimized to obtain high-quality heteronuclear NMR
      spectra of nitrogen-15 isotope-labeled constructs, which are typical of well
      folded monomeric proteins. Moreover, NMR binding studies and functional data
      directly support the correct folding of these fragments.

PMID- 11579227
TI  - An approach for protein to be completely reversible to thermal denaturation even
      at autoclave temperatures.
AB  - Reversibility of protein denaturation is a prerequisite for all applications that
      depend on reliable enzyme catalysis, particularly, for using steam to sterilize
      enzyme reactors or enzyme sensor tips, and for developing protein-based devices
      that perform on-off switching of the protein function such as enzymatic activity,
      ligand binding and so on. In this study, we have successfully constructed an
      immobilized protein that retains full enzymatic activity even after thermal
      treatments as high as 120 degrees C. The key for the complete reversibility was
      the development of a new reaction that allowed a protein to be covalently
      attached to a surface through its C-terminus and the protein engineering approach
      that was used to make the protein compatible with the new attachment chemistry.

PMID- 11579228
TI  - Modular construction of extended DNA recognition surfaces: mutant DNA-binding
      domains of the 434 repressor as building blocks.
AB  - Single-chain derivatives of the 434 repressor containing one wild-type and one
      mutant DNA-binding domain recognize the general operator ACAA-6 base pairs-NNNN,
      where the ACAA operator subsite is contacted by the wild-type and the NNNN
      tetramer by the mutant domain. The DNA-binding specificities of several single
      chain mutants were studied in detail and the optimal subsites of the mutant
      domains were determined. The characterized mutant domains were used as building
      units to obtain homo- and heterodimeric single-chain derivatives. The DNA-binding
      properties of these domain-shuffled derivatives were tested with a series of
      designed operators of NNNN-6 base pairs-NNNN type. It was found that the binding
      specificities of the mutant domains were generally maintained in the new
      environments and the binding affinities for the optimal DNA ligands were high
      (with K(d) values in the range of 10(-11)-10(-10) M). Considering that only
      certain sequence motifs in place of the six base pair spacer can support optimal
      contacts between the mutant domains and their subsites, the single-chain 434
      repressor mutants are highly specific for a limited subset of 14 base pair long
      DNA targets.

PMID- 11579229
TI  - Analysis of the effect of accumulation of amino acid replacements on activity of
      3-isopropylmalate dehydrogenase from Thermus thermophilus.
AB  - A newly selected cold-adapted mutant 3-isopropylmalate dehydrogenase (IPMDH) from
      a random mutant library was a double mutant containing the mutations I11V and
      S92F that were found in cold-adapted mutant IPMDHs previously isolated. To
      elucidate the effect of each mutation on enzymatic activity, I11V and six
      multiple mutant IPMDHs were constructed and analyzed. All of the multiple mutant
      IPMDHs were found to be improved in catalytic activity at moderate temperatures
      by increasing the k(cat) with a simultaneous increase of K(m) for the coenzyme
      NAD(+). k(cat) was improved by a decrease in the activation enthalpy, DeltaH( not
      equal). The multiple mutants did not show large reduction in thermal stability,
      and one of them showed enhanced thermal stability. Mutation from I11 to V was
      revealed to have a stabilizing effect. Mutants showed increased thermal stability
      when the mutation I11V was combined. This indicates that it is possible to
      construct mutants with enhanced thermal stability by combining stabilizing
      mutation. No additivity was observed for the thermodynamic properties of
      catalytic reaction in the multiple mutant IPMDHs, implying that the structural
      changes induced by the mutations were interacting with each other. This indicates
      that careful and detailed tuning is required for enhancing activity in contrast
      to thermal stability.

PMID- 11579230
TI  - Fat hedgehogs, slower or richer?
AB  - Hedgehog (Hh) is a protein ligand that is involved in early developmental
      patterning. The activity of Hh is controlled by cleavage events and various
      posttranslational modifications, including the addition of cholesterol and
      palmitic acid. Van den Heuvel describes how acylation of Hh affects the activity
      of the protein and explores the differences in activity between the vertebrate
      sonic hedgehog (Shh) and Drosophila Hh.

PMID- 11579231
TI  - Ypt/rab gtpases: regulators of protein trafficking.
AB  - Ypt/Rab guanosine triphosphatases (GTPases) have emerged in the last decade as
      key regulators of protein transport in all eukaryotic cells. They seem to be
      involved in all aspects of vesicle trafficking: vesicle formation, motility, and
      docking, and membrane remodeling and fusion. The functions of Ypt/Rabs are
      themselves controlled by upstream regulators that stimulate both their nucleotide
      cycling and their cycling between membranes. Ypt/Rabs transmit signals to
      downstream effectors in a guanosine triphosphate (GTP)-dependent manner. The
      identity of upstream regulators and downstream effectors is known for a number of
      Ypt/Rabs, and models for their mechanisms of action are emerging. In at least two
      cases, Ypt/Rab upstream regulators and downstream effectors are found together in
      a single complex. In agreement with the idea that Ypt/Rabs function in all
      aspects of vesicular transport, their diverse effectors have recently been shown
      to function in all identified aspects of vesicle transport. Activators and
      effectors for individual Ypt/Rabs share no similarity, but are conserved between
      yeast and mammalian cells. Finally, cross talk demonstrated among the various
      Ypt/Rabs, and between Ypt/Rabs and other signaling factors, suggests possible
      coordination among secretory steps, as well as between protein transport and
      other cellular processes.

PMID- 11579232
TI  - Judging a protein by more than its name: GSK-3.
AB  - As knowledge of cellular signal transduction has accumulated, general truisms
      have emerged, including the notion that signaling proteins are usually activated
      by stimuli and that they, in turn, mediate the actions of specific agonists.
      Glycogen synthase kinase-3 (GSK-3) is an unusual protein-serine kinase that bucks
      these conventions. This evolutionarily conserved protein kinase is active in
      resting cells and is inhibited in response to activation of several distinct
      pathways, including those acting by elevation of 3' phosphorylated
      phosphatidylinositol lipids and adenosine 3'-5'-monophosphate (cAMP). In
      addition, GSK-3 is distinctly regulated by, and is a core component of, the Wnt
      pathway. This review describes the unique characteristics of this decidedly
      oddball protein kinase in terms of its diverse biological functions, plethora of
      targets, role in several human diseases, and consequential potential as a
      therapeutic target.

PMID- 11579233
TI  - Wnts, signaling and sulfates.
AB  - Questions remain about the signaling pathways that control pattern formation
      during development. Blair describes how sulfated glycosaminoglycans affect
      several developmentally important signaling pathways, including Wnt-Wingless,
      Fibroblast growth factor, Hedgehog, and Bone morphogenetic protein-4 signaling. A
      new secreted sulfatase, Qsulf1, regulates the sensitivity of vertebrate cells to
      Wnts, possibly by modifying the sulfation of glycosaminoglycans.

PMID- 11579234
TI  - Raf-1 without MEK?
AB  - The Ras-Raf-MEK [(mitogen-activated protein kinase (MAPK) or extracellular signal
      regulated kinase (ERK) kinase]-MAPK signaling pathway controls the activation of
      many cellular functions. Recent reports of Raf-1-deficient mice have indicated
      that MEK may not be an important downstream substrate for Raf-1 and that, in
      fact, Raf-1 is important for blocking apoptosis rather than for cell
      proliferation. Murakami and Morrison examine these recent findings and discuss
      their implications, as well as other possible conclusions that may be drawn from
      the published data.

PMID- 11579235
TI  - Poor CD4 T cell restoration after suppression of HIV-1 replication may reflect
      lower thymic function.
AB  - OBJECTIVE: To characterize immune phenotype and thymic function in HIV-1-infected
      adults with excellent virologic and poor immunologic responses to highly active
      antiretroviral therapy (HAART). METHODS: Cross-sectional study of patients with
      CD4 T cell rises of > or = 200 x 10(6) cells/l (CD4 responders; n = 10) or < 100
      x 10(6) cells/l (poor responders; n = 12) in the first year of therapy. RESULTS:
      Poor responders were older than CD4 responders (46 versus 38 years; P < 0.01)
      and, before HAART, had higher CD4 cell counts (170 versus 35 x 106 cells/l; P =
      0.11) and CD8 cell counts (780 versus 536 x 10(6) cells/l; P = 0.02). After a
      median of 160 weeks of therapy, CD4 responders had more circulating naive
      phenotype (CD45+CD62L+) CD4 cells (227 versus 44 x 10(6) cells/l; P = 0.001) and
      naive phenotype CD8 cells (487 versus 174 x 10(6) cells/l; P = 0.004) than did
      poor responders (after 130 weeks). Computed tomographic scans showed minimal
      thymic tissue in 11/12 poor responders and abundant tissue in 7/10 responders (P
      = 0.006). Poor responders had fewer CD4 cells containing T cell receptor excision
      circles (TREC) compared with CD4 responders (2.12 versus 27.5 x 10(6) cells/l; P
      = 0.004) and had shorter telomeres in CD4 cells (3.8 versus 5.3 kb; P = 0.05).
      Metabolic labeling studies with deuterated glucose indicated that the lower
      frequency of TREC-containing lymphocytes in poor responders was not caused by
      accelerated proliferation kinetics. CONCLUSION: Poor CD4 T cell increases
      observed in some patients with good virologic response to HAART may be caused by
      failure of thymic T cell production.

PMID- 11579236
TI  - T cell receptor excision circle (TREC) content following maximum HIV suppression
      is equivalent in HIV-infected and HIV-uninfected individuals.
AB  - BACKGROUND: The adult human thymus contributes to de novo T cell synthesis; such
      synthesis can be assessed by analyzing T cell receptor excision circles (TREC).
      METHODS: TREC levels were measured in total peripheral blood mononuclear cells
      (PBMC) and CD4- and CD8-enriched cells of 29 HIV-positive patients with maximal
      viral suppression. The expression of CD45RA+CD45RO-, CD45RA+CD62L+, CD45RO
      CD27+CD95low and HLA-DR+CD38+ was assessed using three-color flow cytometric
      analysis of whole blood. Thymic index score was based on computed tomographic
      scans of the thymus. The relationship of TREC with thymic index and the
      expression of the naive phenotypes was evaluated. RESULTS: TREC expression was
      not statistically different in these HIV-positive patients from that in age
      matched HIV-negative controls. Among HIV-positive patients with CD4 cell count of
      > 500 x 10(6) cells/l after antiretroviral therapy (n = 15), PBMC TREC levels
      correlated with the expression of CD45RA+CD45RO- and CD45RA+CD62L+ naive
      phenotypes, and inversely correlated with the expression of HLA-DR+CD38+. The
      change between pre- and post-therapy CD4 cell counts for these 15 patients
      significantly correlated with both thymic index and expression of the
      CD45RA+CD45RO- phenotype. CONCLUSIONS: The finding that TREC expression was
      equivalent between HIV-positive patients after therapy and HIV-negative donors
      suggests that there is no reduction in thymic output among HIV-positive
      individuals after therapy. Given that TREC is inversely correlated with HLA
      DR/CD38 expression, its analysis in studies of thymopoiesis should be evaluated
      in the context of maximum viral suppression to reduce HIV-mediated immune
      activation and/or by normalizing for cell turnover.

PMID- 11579237
TI  - CD4 T cell expansions are associated with increased apoptosis rates of T
      lymphocytes during IL-2 cycles in HIV infected patients.
AB  - OBJECTIVE AND DESIGN: In an attempt to determine the mechanisms underlying the
      CD4 T cell expansions in patients receiving intermittent interleukin (IL)-2, a
      cohort of 10 HIV infected patients were studied during a 5-day cycle of IL-2 to
      measure rates of apoptosis, the expression of activation markers in CD4 and CD8 T
      cell subsets and the serum levels of proinflammatory cytokines. All patients were
      receiving highly active antiretroviral therapy. METHODS: Peripheral blood
      mononuclear cells were tested pre- and at the completion of IL-2 treatment with
      annexin V/7-AAD for the measurement of apoptosis. Phenotypic analyses of T
      lymphocytes were performed in parallel. Serum levels of interferon (IFN)gamma,
      granulocyte-macrophage colony stimulating factor, IL-6 and tumor necrosis factor
      (TNF)alpha were tested by enzyme-linked immunosorbent assay. RESULTS: IL-2
      increased the spontaneous apoptosis rates of CD4 and CD8 T lymphocytes (P =
      0.003). Expression of HLA-DR, CD38 and CD95 increased on both CD4 and CD8 T
      lymphocytes whereas CD25 induction was observed exclusively on CD4 T cells.
      Significant increases of serum IL-6 and TNFalpha levels were noted in all
      patients whereas viral loads remained unchanged. CONCLUSION: Administration of IL
      2 for 5 days in HIV infected patients leads to enhanced apoptosis of both CD4 and
      CD8 T cells despite an eventual increase of the CD4 T cell count. A profound
      activation state with induction of activation markers on T cells and high levels
      of TNFalpha and IL-6 accompanies the increased apoptosis during the IL-2 cycle.
      These data suggest that the CD4 expansions seen in the context of intermittent IL
      2 therapy are the net result of increases in both cell proliferation and cell
      death.

PMID- 11579238
TI  - Prevalence of resistance mutations in antiretroviral-naive chronically HIV
      infected patients in 1998: a French nationwide study.
AB  - OBJECTIVE: To estimate the prevalence of resistance-conferring mutations to
      antiretroviral drugs in previously untreated patients with chronic HIV-1
      infection as a basis for French recommendations on viral genotyping before
      antiretroviral treatment initiation. DESIGN: Resistance mutations were sought in
      samples from 404 patients seen in 23 specialized centres throughout metropolitan
      France in 1998. METHODS: The protease and reverse transcriptase (RT) genes of
      plasma virions were sequenced. Primary and secondary protease and RT gene
      mutations were identified from the International AIDS Society resistance testing 
      USA panel. RESULTS: The prevalence of patients with primary and secondary
      mutations were 3.7% (95% CI 1.7-5.7) and 50.3% (95% CI 45.0-55.6), respectively.
      The prevalence of patients with mutations associated with resistance to
      nucleoside RT inhibitors (NRTI) and non-nucleoside RT inhibitors was 3.3% (95% CI
      1.5-5.1) and 0.8% (95% CI 0.0-1.7), respectively. The prevalence of patients with
      NRTI primary mutations differed according to whether seropositivity had been
      diagnosed more or less than one year previously (0.2 versus 2.2% P = 0.023).
      Primary mutations associated with protease inhibitor resistance occurred at a
      prevalence of 1.9% (95% CI 0.5-3.4) with no difference according to the duration
      of known seropositivity. CONCLUSION: In France, in 1998, the prevalence of
      patients with primary mutations associated with resistance to antiretroviral
      drugs was low. Genotyping before the initiation of therapy was not recommended in
      chronically HIV-1-infected naive patients. A national sentinel survey of
      resistance in this clinical setting is performed regularly to update the
      recommendations for resistance testing.

PMID- 11579240
TI  - Soluble cerebrospinal fluid factors induce Ca2+ dysregulation in rat cultured
      cortical astrocytes in HIV-1-associated dementia complex.
AB  - OBJECTIVES: To investigate the effect of cerebrospinal fluid (CSF) of HIV-1
      seropositive patients with and without HIV-1-associated dementia complex (HADC)
      on the intracellular Ca2+ regulation of cultured cortical astrocytes. DESIGN: In
      a blinded study the effects of CSF samples from HADC patients and from HIV-1
      seropositive but not demented patients on intracellular Ca2+ regulation of
      cultured cortical astrocytes were investigated. Astrocytes were chosen because
      they contribute to both electrophysiological and immunological processes within
      the brain. METHODS: Astrocytes were incubated in CSF samples for 1 h, loaded with
      the Ca2+ indicator dye Fura-2 and intracellular Ca2+ responses upon glutamate
      application were measured. RESULTS: CSF samples from 10 out of 11 HADC patients
      induced a significant reduction of the intracellular Ca2+ increase upon glutamate
      application. On the contrary, seven out of 10 CSF samples from HIV-1-seropositive
      patients without HADC as well as 10 out of 10 CSF samples from HIV-1-seronegative
      controls did not affect the intracellular Ca2+ response. CONCLUSIONS: Our data
      strongly confirm the hypothesis that CSF samples of HADC patients contain soluble
      factors which interfere with the function of astrocytes. These factors may
      include HIV-1 proteins, locally released cytokines or neurotoxins.

PMID- 11579239
TI  - Chronic hepatitis C in HIV infection: feasibility and sustained efficacy of
      therapy with interferon alfa-2b and tribavirin.
AB  - BACKGROUND: The role combination therapy with interferon alfa-2b and tribavirin
      (US: ribavirin) plays in producing sustained virological responses in patients
      with HIV and chronic hepatitis C (HCV) infection is still unknown. OBJECTIVES: To
      determine the feasibility and sustained response of interferon alfa-2b and
      tribavirin combination therapy. DESIGN: Phase II study. METHODS: Seventeen
      patients were enrolled at the National Cancer Institute, Aviano, Italy and
      received combination therapy with interferon alfa-2b 3 MIU subcutaneously three
      times a week plus tribavirin 1000-1200 mg/day for 24 weeks. Antiretroviral
      therapy was concomitantly given in all but one patient. RESULTS: At the end of
      treatment, five (31%) patients achieved clearance of HCV RNA and 11 (69%) showed
      normalized liver function enzyme levels. In three patients, serum HCV RNA
      concentration was still undetectable 24 weeks after treatment, with an overall
      sustained virological response rate of 19% The serum liver enzymes were still
      normal in 10 patients 24 weeks after treatment, the overall sustained biochemical
      response rate being 62% All patients with HCV RNA clearance at the end of
      treatment and 24 weeks after treatment had a concomitant biochemical response.
      Overall the combination treatment was well tolerated. CONCLUSIONS: Our data
      confirm that the combination of interferon alfa-2b and tribavirin is well
      tolerated and feasible in patients with HIV-HCV co-infection and it can be
      associated safely with highly active antiretroviral therapy. The sustained
      response achieved with the drug combination does not seem to be any better than
      that achieved with 12 months of monotherapy with interferon alfa-2b.

PMID- 11579241
TI  - Response to first protease inhibitor- and efavirenz-containing antiretroviral
      combination therapy. The Swiss HIV Cohort Study.
AB  - OBJECTIVE: To compare the response to protease inhibitor (PI) and efavirenz
      containing combination therapy among treatment-naive HIV-infected persons.
      DESIGN: Prospective observational cohort study. METHODS: Response to treatment
      was analysed according to the intent-to-treat principle among antiretroviral
      naive patients who started either efavirenz (n = 89) or PI (n = 183) plus two
      nucleoside reverse transcriptase inhibitors between February 1999 and March 2000
      using Kaplan-Meier and multivariable Cox proportional hazard regression methods.
      Primary endpoint was time to undetectable plasma viral load. Secondary endpoints
      included the number of CD4 cells gained, virological rebound, treatment change,
      and clinical progression. RESULTS: Patients on PI regimens had lower median CD4
      counts (165 versus 216 x 5 106/l; P = 0.15) and were more likely to have AIDS at
      initiation of treatment (25% versus 15% P = 0.048) than patients starting
      efavirenz regimens. The probability of reaching plasma HIV-1 RNA < 400 copies/ml
      was higher with efavirenz- than with PI-containing regimens [adjusted hazard
      ratio, 1.75; 95% confidence interval (CI), 1.34-2.29]. Median times to
      undetectable viral load were 58 days (95% CI, 44-70 days) for efavirenz-treated
      and 88 days (95% CI, 79-98 days) for PI-treated patients. The median number of
      CD4 cells gained in the first 6 months (90 x 10(6) cells/l with efavirenz, 10(7)
      x 10(6) cells/l with PI; P = 0.63), time to and reasons for treatment change,
      time to viral rebound, drug intolerance and clinical progression rates were
      similar in the two treatment groups. CONCLUSIONS: Treatment with efavirenz-,
      compared with PI-based regimens, appeared to result in a superior virological
      response but no difference in immunological or clinical efficacy. The relevance
      of these observations remains to be determined in studies with longer follow-up.

PMID- 11579242
TI  - Mitochondrial DNA decrease in subcutaneous adipose tissue of HIV-infected
      individuals with peripheral lipoatrophy.
AB  - OBJECTIVE: To determine whether the peripheral fat wasting (lipodystrophy), which
      is seen in association with highly active antiretroviral therapy (HAART) that
      includes a nucleoside reverse transcriptase inhibitor (NRTI), is associated with
      a decrease in subcutaneous adipose tissue mitochondrial DNA (mtDNA) content or
      with large mtDNA deletions or insertions. DESIGN: A four cohort cross-sectional
      study. METHODS: The mtDNA content of subcutaneous fat tissue from the neck,
      abdomen and thigh was determined by polymerase chain reaction utilizing the
      amplification of three different mtDNA fragments. The results from HIV-infected
      patients with peripheral fat wasting following more than 6 months of NRTI
      containing HAART were compared with the results from three different control
      cohorts: HIV-infected patients with a similar treatment history without
      lipodystrophy; HIV-infected patients naive to antiretroviral therapy and HIV sero
      negative participants. RESULTS: A decrease in mtDNA content was found in HAART
      treated HIV-infected patients with peripheral fat wasting in comparison with
      subjects in the control cohorts. No large mitochondrial deletions or insertions
      were found. CONCLUSIONS: Lipodystrophy with peripheral fat wasting following
      treatment with NRTI-containing HAART is associated with a decrease in
      subcutaneous adipose tissue mtDNA content.

PMID- 11579243
TI  - HIV protease inhibitor substitution in patients with lipodystrophy: a randomized,
      controlled, open-label, multicentre study.
AB  - BACKGROUND: Lipodystrophy, dyslipidaemia and insulin resistance often complicate
      protease inhibitor-containing antiretroviral therapy. The aims of this study were
      to determine if these are reversible with continued HIV suppression following
      protease inhibitor substitution. METHODS: Eighty-one HIV protease inhibitor
      recipients (78 male; mean antiretroviral therapy, 55 months) with predominant
      peripheral lipoatrophy, HIV RNA < 400 copies/ml plasma for at least the preceding
      6 months, and no prior abacavir, non-nucleoside analogue or adefovir therapy were
      randomized 3 : 2 to continue nucleoside analogues and substitute protease
      inhibitor(s) with abacavir, nevirapine, adefovir and hydroxyurea (n = 49) or to
      continue all therapy (n = 32) with an option to switch at week 24. The primary
      endpoints were total body fat and HIV RNA at week 24. Other assessments were
      regimen safety, regional body composition, metabolic parameters, quality of life,
      and CD4 T-lymphocyte counts to week 48. RESULTS: There was a greater decline in
      total body fat in the switch group than in the continue group (-1.6 and -0.4 kg,
      respectively at week 24; P = 0.006). This comprised greater declines in limb and
      subcutaneous abdominal fat, and in intra-abdominal fat of patients with moderate
      or severe abdominal fat accumulation. Viral suppression was similar, despite 18
      (37%) switch group patients ceasing at least one study drug by week 24 because of
      adverse events. Total cholesterol and triglycerides declined more in the switch
      group (both P < 0.002). High density lipoprotein cholesterol increased
      significantly in both groups at week 48 (P < 0.02). There was no change for any
      glycaemic parameter. CONCLUSIONS: In predominantly lipoatrophic patients,
      switching from HIV protease inhibitor therapy lead to improved lipids and less
      intra-abdominal fat, but also to less peripheral fat, and had minimal effect on
      insulin resistance. Virological control in these heavily pretreated patients was
      unaffected, despite frequent switch drug cessations.

PMID- 11579244
TI  - Bone mineral loss through increased bone turnover in HIV-infected children
      treated with highly active antiretroviral therapy.
AB  - OBJECTIVES: To evaluate the occurrence and define the aetiology of osteopenia in
      children receiving highly active antiretroviral therapy (HAART). METHODS: Bone
      mineral density (BMD) of total body and lumbar spine (L2-L4) was assessed by dual
      energy X-ray absorptiometry in 40 children vertically infected with HIV: 35
      taking HAART and five naive to any antiretroviral treatment (untreated). Six
      HAART-treated children showed clinical evidence of lipodystrophy. N-terminal
      propeptide of type-I procollagen (PINP), bone-specific alkaline phosphatase
      (BALP) and N-terminal telopeptide of type I collagen (NTx) were measured. Results
      were compared with those obtained in 314 healthy controls. Differences between
      HIV-positive and healthy children and within the HIV-positive group were assessed
      by multivariate analyses, controlling for confounding variables (age, sex, weight
      and height). RESULTS: HAART-treated children showed lower spine BMD values than
      untreated (P = 0.045) and healthy (P = 0.004) children and lower total body BMD
      values than untreated (P = 0.012) and healthy (P < 0.0001) children. Spine and
      total body BMD were similar between untreated and healthy children. Total body
      BMD was lower (P < 0.005) in HAART-treated children with lipodystrophy than in
      untreated patients, while children on HAART but without lipodystrophy had
      intermediate values. BALP, PINP and NTx were similar among untreated and healthy
      children. HAART-treated children had higher BALP levels than healthy (P = 0.0007)
      and untreated (P = 0.045) children. PINP values showed the same trend as BALP.
      HAART-treated children had higher NTx urine levels than healthy (P < 0.0001) and
      untreated (P = 0.041) children. CONCLUSIONS: HAART seems a new risk factor for
      life-long osteoporosis in children. An increased rate of bone turnover causes BMD
      decrease. Severity of osteopenia seems to be related to lipodystrophy.

PMID- 11579245
TI  - Viral load as an independent risk factor for opportunistic infections in HIV
      infected adults and adolescents.
AB  - OBJECTIVE: We investigated whether HIV plasma RNA (viral load; VL) predicts risk
      for opportunistic infections (OI) in HIV-infected persons, independent of CD4
      lymphocyte count and other factors that might affect disease outcome. METHODS:
      Among persons who had initiated antiretroviral therapy (ART), we studied the risk
      for OI following a VL measurement in the Centers for Disease Control and
      Prevention Adult and Adolescent Spectrum of HIV Disease (ASD) Project, a medical
      record review study of HIV-infected persons in 11 US cities. Analysis was limited
      to persons who had initiated ART and who had VL data, primarily from the period
      1996-1999. Persons were considered at risk for OI for 1 to 6 months after a given
      VL; risk for OI was assessed using a Poisson multiple regression model
      controlling for CD4 lymphocyte count, ART, and other variables potentially
      associated with development of OI: history of AIDS OI, age, sex, race, HIV risk
      category, OI prophylaxis, and calendar year. RESULTS: Although decreasing CD4
      count was the strongest predictor of risk for OI [relative risk (RR), 13.3 for
      persons with CD4 lymphocyte count < 50 x 10(6)/l compared with persons with CD4
      lymphocyte count > or = 500 x 10(6)/l], increasing VL was independently
      associated with increased risk [RR, 1.6, 1.9, 2.7, and 3.5 for VL of 7000-19 999,
      20 000-54 999, 55 000-149 999, and > or = 150 000 copies/ml (by reverse
      transcription-PCR), respectively, compared with VL < 400]. Similar results were
      obtained when the risk period was reduced to 5, 4, 3, and 2 months after VL
      measurement. CONCLUSIONS: VL is an independent risk factor for OI and should be
      considered in special situations, such as in decisions to discontinue primary or
      secondary OI prophylaxis after CD4 lymphocyte counts have increased in response
      to ART.

PMID- 11579246
TI  - Acceptability and feasibility of Micralax applicators and of methyl cellulose gel
      placebo for large-scale clinical trials of vaginal microbicides.
AB  - OBJECTIVE(S): To evaluate the feasibility and acceptability of the Micralax
      applicator and of methyl cellulose placebo gel for use in vaginal microbicide
      clinical trials. DESIGN: A two-centre prospective study following women for 2
      months. SETTING: Two primary health care clinics in South Africa. PATIENTS,
      PARTICIPANTS: Female volunteers (n = 28) 18 years or older who were HIV negative
      and had no clinically detectable genital tract abnormalities or reproductive
      tract infections. INTERVENTIONS: Participants used pre-filled Micralax
      applicators to apply methyl cellulose gel every other day, as well as up to 1 h
      before to every episode of vaginal sex. MAIN OUTCOME MEASURE(S): Consistency in
      the weight of gel dispensed per application; side-effects attributed to
      applicator or gel use; and acceptability of the applicator and of the gel.
      RESULTS: Over a 2 month follow-up period the 22 women completing the study
      reported no adverse events related to gel or applicator use. The Micralax
      applicator proved acceptable. The gel was not too messy and did not reduce sexual
      frequency or pleasure. On average, the applicator dispensed 4.7 ml per use (close
      to the 4 ml planned). CONCLUSIONS: The Micralax applicator performs well as a
      delivery system for potential vaginal microbicides; and methyl cellulose is an
      appropriate placebo for future microbicide trials.

PMID- 11579247
TI  - Nevirapine and the risk of Stevens-Johnson syndrome or toxic epidermal
      necrolysis.
AB  - OBJECTIVE: To draw attention to the many cases of Stevens-Johnson syndrome (SJS)
      or toxic epidermal necrolysis (TEN) related to nevirapine detected in a
      multinational case-control study of SJS and TEN. METHODS: Actively detected cases
      and matched hospital controls were interviewed for exposure to drugs and other
      risk factors. Data were analysed with case-control and case-crossover methods.
      RESULTS: Between May 1997 and November 1999, a diagnosis of SJS or TEN was
      established in 246 patients. Eighteen were known to be infected by HIV-1 (7.3%),
      15 out of these 18 had been exposed to nevirapine. The reaction began 10-240 days
      after the introduction of nevirapine (median, 12 days) and all patients had
      received escalating doses. In 10 patients the reaction occurred with the initial
      dosage. All but one patients received simultaneously a variety of other
      antiretroviral agents but no specific drug combination emerged, and nevirapine
      was the only drug significantly associated with an increased risk of SJS or TEN
      in HIV-infected persons [odds ratio, 62 (10.4; +infinity) in the case-control
      analysis; odds ratio, +infinity (2.8; +infinity) in the case-crossover analysis].
      CONCLUSIONS: In European countries the risk of SJS or TEN in the context of HIV
      infection appears to be associated with nevirapine. The respect of a lead-in
      period does not appear to prevent SJS or TEN. Because of the severity of these
      reactions and the long elimination half-life of nevirapine, we suggest
      discontinuation of the drug as soon as any eruption occurs.

PMID- 11579248
TI  - Early diagnosis of paediatric HIV-1 infection among African breast-fed children
      using a quantitative plasma HIV RNA assay.
AB  - OBJECTIVE: To evaluate the performance of a quantitative plasma HIV-1 RNA assay
      for HIV infection diagnosis among African breast-fed children. METHODS: Serial
      plasma specimens collected in the first week, at day 45-90, 6 months and 9-12
      months of age from HIV-exposed children born to HIV-1-infected women enrolled in
      the DITRAME ANRS 049a perinatal intervention trial (Abidjan, Cote d'Ivoire) were
      tested for HIV-1 plasma RNA using a branched DNA (bDNA) assay. Sensitivity and
      specificity of this RNA test were assessed in comparison with a qualitative DNA
      polymerase chain reaction (PCR) performed on the same blood samples and allowing
      a reliable detection of the predominant subtype A. RESULTS: Among 91 samples from
      53 infected children which tested positive by DNA PCR, the sensitivity of the
      bDNA test was 100% [95% confidence interval (CI), 96.0-100.0] at < or = 8 days (n
      = 19), 6-12 weeks (n = 43), 6 months (n = 26), and 9-12 months (n = 3). The
      median plasma HIV-1 RNA viral load ranged from 242 000 copies/ml at < or = 8 days
      to more than 500 000 copies/ml at day 45-90 and at 6 months. Of 106 specimens
      from 106 uninfected children who were DNA PCR- negative at month 3 or 6 of age,
      HIV-1 RNA was undetectable in 103, yielding an overall specificity for the bDNA
      test of 97.2% (95% CI, 92.0-99.4). The viral load in the three remaining samples
      with false-positive results was low (410, 937 and 3752 copies/ml, respectively).
      CONCLUSIONS: The quantitative bDNA assay appears a suitable tool for early,
      reliable and easy diagnosis of paediatric HIV-1 infection among a population of
      African breast-fed children.

PMID- 11579249
TI  - Maternal mortality associated with tuberculosis-HIV-1 co-infection in Durban,
      South Africa.
AB  - OBJECTIVES: To document the impact of tuberculosis and HIV-1 on maternal
      mortality. DESIGN: Prospective study, 1997 and 1998; retrospective analysis,
      1996. PARTICIPANTS: Known maternal deaths, defined as the death of a mother
      within a year post-delivery, were studied in Durban, KwaZulu Natal. The HIV-1
      status, presence of tuberculosis, maternal clinical features and perinatal
      outcomes were documented. The overall as well as HIV-1 and tuberculosis-specific
      maternal mortality rates for the hospital were calculated. The attributable
      fraction of deaths as a result of HIV-1 was calculated in the overall group and
      in those with tuberculosis co-infection. RESULTS: A total of 50 518 deliveries
      and 101 maternal deaths were recorded. Of the deaths, 29.7% (30/101) were HIV-1
      infected. The overall mortality rate was 200/100 000; for HIV-1-infected women
      this was 323.3/100 000, HIV-1-negative mothers, 148.6/100 000 live births. The
      attributable fraction of overall deaths as a result of HIV-1 was 15.9% Fourteen
      of the 15 mothers with tuberculosis were HIV-1 co-infected. The mortality rate
      for tuberculosis and HIV-1 co-infection was 121.7/1000; for tuberculosis without
      HIV-1 co-infection, 38.5/1000. Fifty-four per cent of maternal deaths caused by
      tuberculosis were attributable to HIV-1 infection. Thirty-five per cent of
      maternal deaths were associated with stillbirths; perinatal outcomes were no
      different between groups of mothers with tuberculosis, HIV-1 or neither
      infection. CONCLUSION: Tuberculosis and HIV-1 are emerging as significant
      contributors to maternal mortality in KwaZulu Natal. Any attempt to improve
      maternal health must also include careful screening and investigation for
      tuberculosis in high-risk pregnant women.

PMID- 11579250
TI  - Predictors of HIV-1 serostatus disclosure: a prospective study among HIV-infected
      pregnant women in Dar es Salaam, Tanzania.
AB  - OBJECTIVES: To examine the socio-demographic and behavioral factors predictive of
      women's disclosure of an HIV-positive test result in Dar es Salaam, Tanzania.
      DESIGN: From April 1995 to May 2000, 1078 HIV-positive pregnant women
      participated in an ongoing randomized trial on micronutrients and HIV-1 vertical
      transmission and progression. Disclosure to a partner or to a female relative was
      assessed 2 months after post-test counseling and at 6 monthly follow-up visits.
      Socio-demographic, health, behavioral and psychological factors were measured at
      baseline and during follow-up. METHODS: Predictors of time to disclosure of HIV
      serostatus were determined using Cox proportional hazards regression models.
      RESULTS: Prevalence of disclosure to a partner ranged from 22% within 2 months to
      40% after nearly 4 years. Women were less likely to disclose to their partners if
      they were cohabiting, had low wage employment, had previously disclosed to a
      female relative, or reported ever-use of a modern contraceptive method. Women
      reporting fewer than six lifetime sexual partners or knowing someone with
      HIV/AIDS were more likely to disclose to their partners. Disclosure to a female
      relative was predicted by knowing more than two individuals with HIV/AIDS, full
      economic dependency on their partner, high levels of social support, and prior
      attendance at a support group meeting. CONCLUSIONS: A substantial proportion of
      HIV-infected pregnant women never disclosed their result to a partner or a close
      female relative. Lack of disclosure may have limited their ability to engage in
      preventive behaviors or to obtain the necessary emotional support for coping with
      their serostatus or illness.

PMID- 11579251
TI  - Integration of tuberculosis screening at an HIV voluntary counselling and testing
      centre in Haiti.
AB  - OBJECTIVE: To describe the integration of tuberculosis screening into the
      activities of an HIV voluntary counselling and testing (VCT) centre in a country
      with endemic tuberculosis. SETTING: An HIV VCT centre in Port au Prince, Haiti.
      DESIGN: All patients presenting for HIV VCT who reported cough received same-day
      evaluation for active tuberculosis. Of the 1327 adults presenting to the centre
      for the first time between January and April 1997, 263 (20%) reported cough and
      of these 241 (92%) were evaluated. RESULTS: Of the 241 patients evaluated for
      cough, 76 (32%) were diagnosed with pulmonary tuberculosis. Of the 76 patients
      diagnosed with pulmonary tuberculosis, 28 (37%) had a positive smear for acid
      fast bacilli (AFB), 14 (18%) had a negative AFB smear but a positive sputum
      culture for Mycobacterium tuberculosis, and 34 (45%) had culture-negative
      tuberculosis. Also, 31 out of 241 (13%) VCT clients evaluated for cough were
      diagnosed with bacterial pneumonia. CONCLUSION: This report confirms that in
      areas with a high HIV and tuberculosis prevalence, a high proportion of VCT
      clients have active pulmonary tuberculosis. The integration of tuberculosis
      screening offers several benefits, including the diagnosis and treatment of large
      numbers of individuals with tuberculosis, a decreased risk of nosocomial
      tuberculosis transmission, and the opportunity to provide tuberculosis
      prophylaxis to HIV-positive patients in whom tuberculosis has been excluded.
      Future studies are needed to determine the cost-effectiveness of integrated
      tuberculosis and HIV VCT services, and whether integration should be recommended
      in all countries with high HIV and tuberculosis rates.

PMID- 11579252
TI  - What limits immune reconstitution in HIV infection? Divergent tools converge on
      thymic function.

PMID- 11579253
TI  - Markers of AIDS dementia complex: the role of cerebrospinal fluid assays.

PMID- 11579254
TI  - Decreased HIV-specific CD4 T cell proliferation in long-term HIV-infected
      individuals on antiretroviral therapy.
AB  - The effect of highly active antiretroviral therapy (HAART) on HIV-specific CD4 T
      cell proliferation in long-term HIV-infected individuals was studied. Subjects
      receiving treatment for over a year were compared with individuals not receiving
      therapy. The absolute number of HIV-specific memory CD4 T cells proliferating in
      response to HIV antigen was substantially higher in untreated subjects than in
      those on HAART. A decrease in HIV-specific memory CD4 T cells could explain the
      rebound in HIV replication after the termination of HAART.

PMID- 11579255
TI  - Highly active antiretroviral therapy induces specific changes in effector and
      central memory T cell sub-populations.
AB  - Highly active antiretroviral therapy (HAART) improves the immunodeficiency of HIV
      infected individuals. In this report we show that HAART increases both naive
      (CD45RA+CD62L+) and central memory (CD45RO+CD62L+) CD4 lymphocytes. On CD8
      lymphocytes, HAART induces an increase of naive cells associated with a
      consistent decrease of effector cells (CD45 RO+CD62L-). No specific differences
      in phenotypic changes were observed with different HAART regimens, suggesting
      that, once viral suppression is achieved, the pharmacological class of
      antiretroviral drugs does not affect immune reconstitution.

PMID- 11579256
TI  - Stromal-cell-derived factor 1 prevents the emergence of the syncytium-inducing
      phenotype of HIV-1 in vivo.
AB  - In a correlative study, the mean plasma level of the chemokine stromal-cell
      derived factor 1 (SDF-1) was lower in subjects with syncytium-inducing (SI) than
      in subjects with non-syncytium-inducing (NSI) HIV isolates, regardless of the CD4
      cell count or when compared with HIV-negative individuals. Individuals with high
      SDF-1 had an 81% probability of having an NSI virus phenotype compared with
      individuals with lower SDF-1. Increased expression of SDF-1 may help explain why
      the more pathogenic SI HIV-1 variants do not appear in some individuals.

PMID- 11579257
TI  - A point mutation in CD45 may be associated with an increased risk of HIV-1
      infection.
AB  - The CD45 antigen is essential for normal antigen receptor-mediated signalling in
      lymphocytes, and different patterns of splicing of CD45 are associated with
      distinct functions in lymphocytes. Here we show that abnormal CD45 splicing
      caused by a C77G transversion in exon A of the gene encoding CD45 (PTPRC) is
      associated with increased susceptibility to HIV-1 infection.

PMID- 11579258
TI  - Changes in the rate of genotypic resistance to antiretroviral drugs in Spain.
AB  - Genotypic resistance to antiretroviral drugs was examined in 684 individuals
      attending 18 outpatient clinics distributed across Spain in June 2000. Compared
      with similar surveys conducted before 1998, the prevalence of resistance to
      nucleosides has declined significantly among naive chronic HIV carriers. In
      contrast, resistance among pre-treated patients has increased; resistance to all
      three drug families having been recognized in nearly a quarter of patients.

PMID- 11579259
TI  - Variation in breastmilk HIV-1 viral load in left and right breasts during the
      first 3 months of lactation.
AB  - The mechanism and risk factors associated with mother-to-child transmission of
      HIV-1 through breastfeeding remain unclear; breastmilk viral load may be an
      important determinant of transmission. Analysis of breastmilk cell-free viral
      load in samples taken from each breast at 1, 6 and 14 weeks postpartum showed
      that HIV-1 is shed intermittently and load may differ considerably between
      breasts of an individual woman at any given time. Breastmilk HIV-1 load was
      undetectable in approximately one-third of samples.

PMID- 11579260
TI  - AIDS-associated mild neurocognitive impairment is delayed in the era of highly
      active antiretroviral therapy.

PMID- 11579261
TI  - Inflammatory reactions in progressive multifocal leukoencephalopathy after highly
      active antiretroviral therapy.
AB  - Three patients with progressive multifocal leukoencephalopathy (PML) treated with
      highly active antiretroviral therapy (HAART) worsened clinically and
      radiologically. At the time of deterioration all three had reduced HIV viraemia
      and increased CD4 cell counts. Brain biopsy in all three disclosed PML and marked
      perivascular lymphoplasmacytic infiltration. We reviewed the slides of 28 brain
      biopsies diagnostic of PML. Inflammatory changes were observed in four out of
      nine patients on HAART and in one out of 19 patients not on HAART.

PMID- 11579262
TI  - Association between Kaposi's sarcoma and atherosclerosis: implications for
      gammaherpesviruses and vascular disease.
AB  - The treatment of HIV-positive patients with protease inhibitors has been
      suggested to increase their risk of atherosclerosis. The cause of this
      accelerated atherogenesis is unknown, but on the basis of previous studies we
      postulated that it could be linked to the presence of human herpesvirus-8. A
      retrospective analysis of post-mortem reports showed a strong correlation between
      Kaposi's sarcoma and the presence of atheroma. This hypothesis merits further
      investigation.

PMID- 11579263
TI  - Psychological impact of structured treatment interruptions in patients with
      prolonged undetectable HIV-1 viral loads.
AB  - Structured treatment interruption strategies may help overcome problems of highly
      active antiretroviral therapy, but might also represent a cause of stress. We
      present data that indicate a psychological benefit from structured treatment
      interruption. Although some disturbances appear at the resumption of therapy, no
      definitive problems are found that preclude such therapeutic approaches from a
      psychological perspective. However, a close follow-up of patients during
      interruption periods is advisable to avoid difficulties reported at treatment
      resumption presenting a risk to patients' health.

PMID- 11579264
TI  - HIV-1 subtype G and BG recombinant viruses in Spanish natives: evidence of
      characteristic mutations in reverse transcriptase and protease.

PMID- 11579265
TI  - Oral clinical markers and viral load in a prospective cohort of Mexican HIV
      infected patients.

PMID- 11579266
TI  - Efavirenz-induced psychosis.

PMID- 11579267
TI  - Pneumocystis carinii pneumonia after cessation of secondary prophylaxis in a
      patient on highly active antiretroviral therapy with a CD4 cell count greater
      than 200/mm3.

PMID- 11579268
TI  - Changing incidence of Kaposi's sarcoma and non-Hodgkin's lymphoma among young men
      in San Francisco.

PMID- 11579269
TI  - Despite the controversy, HIV prenatal testing laws get the job done.

PMID- 11579271
TI  - Indinavir crystallization around the loop of Henle: experimental evidence.
AB  - OBJECTIVE: To determine the probable site of the nephron and the plasma indinavir
      (IDV) concentration at which intrarenal IDV crystallization occurs. DESIGN: We
      performed in vitro crystallization experiments in IDV solutions simulating
      conditions found in the nephron. METHODS: To determine intrarenal IDV
      concentrations at which conditions in the nephron allow crystallization, several
      concentrations of IDV basic solutions (0-800 mM) were titrated from pH 4.0 to
      higher pH values until crystals formed within 1 minute. Based on the combination
      of pH and ionic strength at which crystals formed, we determined the site of the
      nephron at which this combination was first attained. Based on the capacity for
      concentration at that site, we were able to measure the corresponding plasma IDV
      concentration. RESULTS: Under conditions normally found at the proximal tubule
      (i.e., pH 6.7 and ionic strength of 200 mM), IDV crystallized at 200 mg/L. Under
      conditions applying to the loop of Henle, pH 7.4 and ionic strength of 200 mM,
      IDV crystallized at 125 mg/L, which would correspond to a plasma IDV
      concentration of 8 mg/L. CONCLUSIONS: IDV crystallization is most likely in the
      loop of Henle and may already start at plasma IDV concentrations as low as 8
      mg/L. Increasing hydration does not reduce the risk of IDV crystallization in the
      loop of Henle but instead prevents IDV crystallization and aggregation in the
      lower urinary tract. It remains to be confirmed whether prevention of high IDV
      plasma concentrations will reduce the risk of IDV crystallization in the loop of
      Henle.

PMID- 11579270
TI  - Increased replication of HIV-1 at sites of Mycobacterium tuberculosis infection:
      potential mechanisms of viral activation.
AB  - Tuberculosis (TB) enhances HIV-1 replication and the progression to AIDS in
      dually infected patients. We employed pleural TB as a model to understand the
      interaction of the host with HIV-1 during active TB, at sites of Mycobacterium
      tuberculosis (MTB) infection. HIV-1 replication was enhanced both in the cellular
      (pleural compared with blood mononuclear cells) and acellular (pleural fluid
      compared with plasma) compartments of the pleural space. Several potential
      mechanisms for expansion of HIV-1 in situ were found, including augmentation in
      expression of tumor necrosis factor (TNF)-alpha and the HIV-1 noninhibitory beta
      chemokine (MCP-1), low presence of HIV-1 inhibitory beta-chemokines (MIP-1 alpha,
      MIP-1 beta, and RANTES [regulated on activation, normal T expressed and
      secreted]), and upregulation in expression of the HIV-1 coreceptor, CCR5, by
      pleural fluid mononuclear cells. Thus, at sites of MTB infection, conditions are
      propitious both for transcriptional activation of HIV-1 in latently infected
      mononuclear cells, and facilitation of viral infection of newly recruited cells.
      These mechanisms may contribute to enhanced viral burden and dissemination during
      TB infection.

PMID- 11579272
TI  - Failure of a short-term prednisone regimen to prevent nevirapine-associated rash:
      a double-blind placebo-controlled trial: the GESIDA 09/99 study.
AB  - OBJECTIVES: Rash is the most frequent adverse event associated with nevirapine.
      The use of prednisone has been controversial in this setting. A double-blind
      placebo-controlled study was performed to evaluate its efficacy in nevirapine
      induced rash prevention. DESIGN: Multicentered, randomized, double-blind, placebo
      controlled clinical trial with prednisone (30 mg/day x 2 weeks). INCLUSION
      CRITERIA: HIV-1 infection; CD4 count >200 cells/mm3; plasma viral load (PVL) <5
      log10 copies/ml; nevirapine (200 mg/day x 2 weeks, followed by 200 mg twice
      daily) plus stavudine and didanosine. Clinical follow-up was performed at 15, 30,
      and 60 days and thereafter every 2 months. RESULTS: In all, 75 evaluable patients
      were enrolled (39 prednisone/36 placebo). Median baseline CD4 + cell count was
      390 cells/mm3 and PVL, 20,200 copies/ml. Overall, nine cases of rash (12.5%) were
      detected, seven (18%) in the prednisone group and two (5.5%) in the placebo group
      (odds ratio [OR], 3.85; 95% confidence interval [CI], 0.65-29.3; p =.11).
      Incidence of moderate-to-severe rashes leading to nevirapine withdrawal was 13.5%
      (5 of 37) in the prednisone group and 3% (1 of 35) in the placebo group ( p =.2).
      Median time to rash in both groups was 16 days. Adverse events that motivated
      withdrawal of therapy appeared in 6 patients from the prednisone group (15.4%)
      and 3 from the placebo group (8.3%) ( p =.3). CONCLUSION: Short-term prednisone
      administration does not prevent nevirapine rash, but might even increase its
      incidence.

PMID- 11579273
TI  - Changes in neurocognitive performance in a cohort of patients treated with HAART
      for 3 years.
AB  - OBJECTIVES: To describe changes in HIV-associated neurocognitive impairment in
      patients treated with highly active antiretroviral therapy (HAART) for at least 3
      years. METHODS: Prospective, observational study of comprehensive
      neuropsychologic (NP) testing, neurologic examination, and laboratory measures
      before HAART and after 6, 15 and 45 months of HAART, on 28 consecutive patients
      seen in our department since April 1996. RESULTS: At baseline, 16 patients were
      neurocognitively impaired and 12 were not. Among the 16 impaired patients, 5
      patients failed to meet the criteria for impairment after 6 months and 9 patients
      after both 15 and 45 months of HAART, respectively. Statistically significant
      improvements ( p < or =.01) were seen in two of six measures exploring the
      concentration and speed of mental processing, two of three measures exploring
      mental flexibility, in one of five measures exploring memory, and in two of two
      measures exploring fine motor functions. Unimpaired study subjects performed
      better than impaired ones in 10 of 17 measures at baseline, in eight of 17 after
      6 months, in six of 17 after 15 months, and in seven of 17 after 45 months of
      HAART. CONCLUSIONS: During the course of HAART, patients experienced a positive
      and sustained improvement in their neurocognitive performance. However, the
      presence of 7 of 16 (43.7%) patients with neurocognitive impairment, and the
      persistence of statistically significant differences in the neurocognitive
      performance between impaired and unimpaired patients after more than 3 years of
      HAART, suggests that ongoing HIV-related neurologic damage can occur even during
      potent antiretroviral treatment.

PMID- 11579274
TI  - Influence of injection drug use behavior on reported antiretroviral therapy use
      among women in the HIV Epidemiology Research study: on-site versus referral care.
AB  - BACKGROUND: HIV-infected injection drug users consistently report poor
      antiretroviral therapy use and little contact with health care providers. It has
      been suggested that the clinical setting where patients are seen affects the use
      of highly active antiretroviral therapy. OBJECTIVES: The purpose of this study
      was to determine whether ease of access to medical care affects self-report of
      taking antiretroviral therapy, particularly among female injection drug users.
      DESIGN: The study is a cross-sectional analysis from a prospective cohort study
      of HIV-infected women. SETTING: Women were enrolled at four sites in the United
      States: Detroit, Michigan, and Providence, Rhode Island, where on-site HIV care
      and treatment were offered, and Baltimore, Maryland, and the Bronx, New York,
      where all participants were referred elsewhere for HIV care and treatment.
      PATIENTS: Patients were HIV-infected women with no AIDS diagnosis or women who
      were at risk for HIV infection either through self-reported injection drug use
      since 1985 or through sexual contact. MEASUREMENTS: The study measured self
      reported use of antiretroviral therapy (ART) alone or combined with Pneumocystis
      carinii (PCP) prophylaxis in the previous 6 months. RESULTS: In multivariate
      analysis including type of study site (on-site compared with referral care) and
      injection drug use, any self-reported ART use associated with low CD4 cell count
      category, older age, and race. However, at on-site care centers, women were
      equally likely to report ART use regardless of current, former, or no injection
      drug use, whereas at referral sites only women identified as sexual contacts were
      more likely to report any ART use, independent of all other variables.
      CONCLUSIONS: Easy access to medical care has an important impact on HIV-infected
      women receiving ART, particularly those who are active injection drug users.

PMID- 11579275
TI  - Epidemiologic and clinical features of HIV-infected and HIV-uninfected Ugandan
      children younger than 18 months.
AB  - METHODS: Groups of HIV-infected and HIV-uninfected infants younger than 18 months
      (mainly younger than 6 months) were compared to identify clinical features that
      could differentiate the two groups. The HIV-infected group also was compared with
      HIV-infected children older than 18 months. Recruitment was as follows for the
      group younger than 18 months: 708 children admitted with sepsis and clinical
      features suggestive of HIV infection were screened for HIV1 and HIV2 by HIV
      enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR)
      was undertaken on all ELISA-seropositive blood samples (270). HIV infection was
      confirmed in 136 (19.2%), 438 (61.9%) were HIV-seronegative, 27 (3.8%) were HIV
      seroreverters, 36 (5.1%) were HIV-seropositive but PCR negative (uninfected), and
      71 (10.0%) were indeterminate. One hundred thirty-six HIV-infected children were
      compared with 501 uninfected children. Confirmed HIV-infected children older than
      18 months attending the pediatric HIV clinic were compared with the 136 HIV
      infected children younger than 18 months. RESULTS: Under 18 months, the median
      age of HIV-infected children (n = 136) was 4.0 months (range, 3 d -18 mo ) and
      the median age of the uninfected children (n = 501) was 1.0 month (range, 3 d -18
      mo ). HIV-infected children were more likely to have had injections, chloroquine,
      and nystatin, and to have attended a health center or hospital (p <.001). In the
      HIV-infected group, the Z score for weight-for-age was -1.75, length-for-age 
      0.78, and weight-for-length 1.86, significantly lower scores than those of the
      uninfected group, which were -0.60, -0.23, and 3.05, respectively (p <.05). The
      mean head circumference was below the third percentile in 40% of HIV-infected
      compared with 22% of uninfected children (p <.001). Overall, 56 (8%) children had
      marasmus, 6 (0.8%) kwashiorkor, and 3 (0.4%) marasmic kwashiorkor. Sixteen
      percent of the HIV-infected and 7% of uninfected children had marasmus (p <.05).
      The 1989 revised World Health Organization clinical criteria for diagnosis of
      AIDS had sensitivity, specificity, and positive predictive values of 28%, 98%,
      and 93%, respectively. Older than 18 months (n = 109), the median age was 24
      months (range, 18-60 mo ). The following were significantly more common in HIV
      infected children older than 18 months than in those younger than 18 months:
      bacille Calmette-Guerin vaccination scar, parotid enlargement, nonspecific
      generalized dermatitis, and chronic diarrhea ( p <.001). Oral candidiasis was
      more common in the group younger than 18 months (p <.001). In infants examined in
      the hospital for infective conditions, oropharyngeal candidiasis, ear discharge,
      dermatologic disorders, generalized lymphadenopathy, lobar consolidation,
      hepatosplenomegaly, and failure to thrive, especially marasmus, were important
      indicators of HIV infection.

PMID- 11579276
TI  - Differences in difficulty adjudicating clinical events in patients with advanced
      HIV disease.
AB  - Adjudication of clinical events is often used as a quality assurance method in
      clinical research. During the design of the Viral Activation Transfusion Study (a
      clinical trial in patients with advanced HIV disease), a set of study endpoints
      was defined (primarily AIDS-defining conditions), criteria for confirmation of
      each event type were developed, and an adjudication procedure was established.
      The adjudication process included 1) an initial review of documentation of each
      event by two independent reviewers, 2) the opportunity to request additional
      information, 3) a second review either of additional documentation or of cases in
      which there was disagreement on first review, and 4) the consultation of a third
      reviewer if there was still disagreement. Overall, of 288 reported endpoints, 30%
      required additional documentation or more than one review, and 16% were not
      confirmed at the end of the adjudication process. However, these percentages
      varied widely over different types of events. For example, of 30 reported
      nonophthalmalogic cytomegalovirus events, 37% required additional documentation
      and 40% were not confirmed. In contrast, every one of 17 reported Pneumocystis
      cariini pneumonias were confirmed with no requirement for additional
      documentation. The results can be used to help design endpoint documentation and
      adjudication procedures for other studies, thereby improving data quality and
      reducing costs.

PMID- 11579277
TI  - Trust and the acceptance of and adherence to antiretroviral therapy.
AB  - BACKGROUND: Antiretroviral therapy (ART) has resulted in reduced AIDS incidence
      and mortality. Socially marginalized individuals with HIV infection, particularly
      injection drug users (IDUs), have received less ART and derived less benefit than
      others. Little is known about the therapeutic process necessary to promote
      acceptance of and adherence to ART among marginalized HIV-infected populations.
      We report on the correlates of both acceptance of and adherence to ART among HIV
      infected prisoners, most of whom are IDUs. DESIGN: Using a cross-sectional survey
      design within four ambulatory prison HIV clinics, 205 HIV-infected prisoners
      eligible for ART were recruited between March and October 1996. MEASUREMENTS:
      Detailed interviews were conducted that included personal characteristics, health
      status and beliefs, and validated standardized scales measuring depression,
      health locus of control, social desirability and trust in physician, medical
      institutions and society. Acceptance and adherence were documented by self-report
      and validated for a subset by pharmacy review. Clinical information was obtained
      from standardized chart review. Adherence was defined as having taken > or = 80%
      of ART. RESULTS: The acceptance of (80%) and adherence to (84%) ART among this
      group of prisoners was high. Multiple regression models demonstrated that
      correlates of acceptance of and adherence to ART differed. Acceptance was
      associated with trust in physician (8% increase for each unit increase with trust
      in physician scale) and trust in HIV medications (threefold reduction for those
      mistrustful of medication). Side effects (OR = 0.09), social isolation (OR =
      0.08), and complexity of the antiretroviral regimen (OR = 0.33) were associated
      with decreased adherence. The prevalence of health beliefs suggesting an adverse
      relationship between ART and drugs of abuse was high (range 59 to 77%). Adherence
      did not differ among those receiving directly observed therapy (82%) or self
      administration (85%). CONCLUSIONS: ART can be successfully administered within a
      correctional setting. Trust and the therapeutic relationship between patient and
      physician remain central in the ART initiation process. Characteristics of the
      therapeutic agents and the degree of social isolation predict adherence. These
      results may inform the design of interventions to improve both acceptance of and
      adherence to ART particularly among marginalized populations who have not derived
      full benefit from these potent new therapies.

PMID- 11579278
TI  - HIV incidence among repeat HIV testers at a county hospital, San Francisco,
      California, USA.
AB  - OBJECTIVES: To estimate HIV incidence, characterize correlates of HIV
      seroconversion, and monitor temporal trends in HIV transmission among patients
      repeatedly tested for HIV by a county hospital in San Francisco. DESIGN:
      Retrospective longitudinal study. METHODS: HIV incidence was retrospectively
      calculated among persons voluntarily tested for HIV antibody more than once at
      San Francisco's county hospital or one of its affiliated satellite community
      clinics between 1993 and 1999. Linkage of HIV test results in computerized
      databases identified "seroconverters" as individuals who had a negative antibody
      test followed by a positive test. The interval between tests was used as the
      person-time at risk. Cox proportional hazards analysis identified correlates of
      HIV seroconversion. RESULTS: A total of 84 HIV seroconversions were identified
      among 2893 eligible patients repeatedly tested for HIV antibody over a cumulative
      5860 person-years (PYs) (incidence of 1.4 per 100 PYs, 95% confidence interval
      [CI]: 1.2-1.7). The majority of seroconversions (71 [84.5%]) were among injection
      drug users (IDUs) (incidence of 2.0 per 100 PYs, CI: 1.6-2.4). HIV incidence was
      highest among men who have sex with men (MSM) who were also IDUs (incidence of
      3.8 per 100 PYs, CI: 2.7-5.1) and lowest among non-IDUs, heterosexual men, and
      non-IDU women (incidence of 0.3 per 100 PYs, CI: 0.1-0.6). In multivariate
      analysis, correlates of HIV seroconversion were age 25 to 29 years (hazard ratio
      [HR] = 3.9, CI: 2.4-6.3), MSM (HR = 2.9, CI: 1.9-4.4), and IDU (HR = 3.2, CI: 1.8
      5.8). Overall, no temporal trend in annual HIV incidence was noted during the
      study period; however, HIV incidence among MSM IDUs increased from 2.9 per 100
      PYs in 1996 to 4.7 per 100 PYs in 1998. CONCLUSIONS: The rate of seroconversion
      in this hospital and affiliated clinic population is unexpectedly high. Moreover,
      HIV transmission among IDU patients has not decreased over the last several
      years. The San Francisco county hospital provides a high-risk sentinel population
      to monitor emerging trends in HIV transmission, especially among IDUs, and
      presents multiple opportunities for prevention interventions, because these
      patients are being seen repeatedly by clinicians.

PMID- 11579280
TI  - Trends in HIV-related inpatient admissions from 1993 to 1997: a seven-state
      study.
AB  - BACKGROUND AND OBJECTIVES: Reports of declining HIV-related inpatient use have
      typically been based on limited or local data. Using comprehensive hospital
      discharge data from seven states, this study examines trends in HIV-related
      inpatient admission rates and lengths of stay from 1993 through 1997. METHODS: We
      identified HIV-related admissions by the International Classification of
      Diseases, ninth edition (ICD-9-CM) diagnosis codes in the range 042 to 044.
      Analyses assessed effects of state, gender, race/ethnicity, insurance, and time
      period; they also examined differential patterns of change. RESULTS: HIV-related
      inpatient admission rates rose between 1993 and 1995 but began declining steadily
      starting in late 1995. This general pattern occurred for all states, demographic
      groups, and insurers. The magnitude of the decline varied; admissions for white
      males and for patients with private insurance showed the greatest decreases.
      Admission rates were highest for African-American males and lowest for white
      females. Lengths of stay declined steadily; trends did not differ by demographic
      group or payer. CONCLUSIONS: Results document the recent decline in HIV-related
      hospital admission rates. Relative declines in admissions parallel reported
      disparities in access to new antiretroviral therapies. Racial/ethnic disparities
      in inpatient use persist.

PMID- 11579279
TI  - Maternal characteristics associated with antenatal, intrapartum, and neonatal
      zidovudine use in four US cities, 1994-1998.
AB  - OBJECTIVES: To evaluate implementation of 1994 United States Public Health
      Service guidelines for zidovudine (ZDV) use in HIV-infected women and their
      newborns by describing the prevalence of use of perinatal ZDV and other
      antiretrovirals and by investigating determinants of not receiving perinatal ZDV.
      DESIGN/METHODS: The Perinatal AIDS Collaborative Transmission Study is a
      prospective cohort study designed to collect information related to mother-to
      child HIV transmission that was conducted in New York City (NY), Newark (NJ),
      Baltimore (MD), and Atlanta (GA), U.S.A. The current analysis was restricted to
      infants born between July 1994 and June 1998. RESULTS: Utilization rates for
      antenatal, intrapartum, and neonatal ZDV increased from 41% to 70% during the 4
      year period. Use of combination antiretrovirals increased from fewer than 2% of
      women in 1994 to 1995 to 35% in 1997 to 1998. Antenatal and neonatal ZDV use
      increased each year, but intrapartum ZDV use reached a plateau after 1996. Mother
      infant pairs with the following characteristics were less likely to have received
      a complete 3-part ZDV regimen: older maternal age, CD4 count >500 cells/microl,
      preterm birth, cocaine or heroin use during pregnancy, positive newborn drug
      screen test result, and smoking or alcohol use during pregnancy. By multivariate
      logistic regression adjusted for hospital and year of birth, cocaine or heroin
      use during pregnancy (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.6
      3.3), maternal CD4 count (OR, 0.4; 95% CI, 0.2-0.8; comparing <200 with >500
      cells/microl), and preterm birth (OR, 1.6; 95% CI, 1.1-2.5) remained
      independently associated with not receiving the complete ZDV regimen.
      CONCLUSIONS: ZDV use by pregnant HIV-infected women and their infants has
      increased dramatically since publication of the 1994 guidelines. Nevertheless,
      women who abuse substances, give birth preterm, or have less advanced
      immunosuppression, were at substantial risk of not receiving the complete ZDV
      regimen.

PMID- 11579281
TI  - Risk factors associated with HIV infection among young gay and bisexual men in
      Canada.
AB  - OBJECTIVE: To assess risk factors associated with HIV prevalence and incidence
      among gay and bisexual men in two prospective Canadian cohorts. METHODS: The
      Vanguard Project and the Omega Cohort are prospective cohort studies of gay and
      bisexual men ongoing in Vancouver and Montreal, respectively. For this analysis,
      baseline sociodemographic characteristics, sexual behavior, and substance use
      data from these two cohorts were combined. Assessment of risk factors for HIV
      seroprevalence and seroconversion were carried out using univariate and
      multivariate analysis. RESULTS: This analysis was based on 1373 gay and bisexual
      men aged 16 to 30 years. Men who were HIV-seropositive at baseline (n = 48) were
      more likely to report living in unstable housing, to have had less than a high
      school education, and to have been unemployed than those who were HIV-negative (n
      = 1325). HIV-positive men were also more likely to report having engaged in
      sexual risk behavior, including having had consensual sex at a younger age,
      having had at least 6 partners during the previous year, ever having been
      involved in the sex trade, and having engaged in unprotected receptive anal
      intercourse. With respect to substance use, HIV-positive men were more likely to
      report the use of crack, cocaine, heroin, and marijuana and to use injection
      drugs. Similarly, men who seroconverted during the course of the studies (n = 26)
      were more likely to report having less than a high school education and having
      lived in unstable housing at baseline. Compared with HIV-negative men, men who
      seroconverted were more likely to report ever having been involved in the sex
      trade and engaging in unprotected receptive anal intercourse. Reports of cocaine
      use and injection drug use were also significantly higher for men who
      seroconverted compared with HIV-negative men. CONCLUSIONS: Our data indicate that
      HIV-positive gay and bisexual men are more likely to be living in unstable
      conditions and to report more risky sexual and substance use behaviors than HIV
      negative men.

PMID- 11579282
TI  - Cruising on the Internet highway.
AB  - This study evaluated differences in sexual behavior and risk for sexually
      transmitted diseases (STDs) among men who have sex with men (MSM) who met their
      partners on-line and those who did not. A self-administered questionnaire on
      sexual behavior was offered to a convenience sample of patients seeking public
      STD services. Thirty-two percent of MSM patients reported meeting a sexual
      partner over the Internet in the past year. MSM with on-line partners were
      younger, more likely to report sex with an HIV-positive person in the last year,
      and more likely to report casual partners in the last year compared with MSM with
      only off-line partners. HIV-negative MSM with on-line partners were more likely
      than HIV-negative MSM with only off-line partners to have received money or drugs
      for sex in the past year and to report sex with an HIV-positive partner in the
      past year. Although meeting partners on the Internet was common and associated
      with increased risk for STDs in MSM, it also presents new untapped opportunities
      for on-line health promotion and disease prevention.

PMID- 11579283
TI  - First molecular characterization of HIV-1 Tunisian strains.
AB  - In order to identify HIV-1 subtypes circulating in Tunisia, blood specimens from
      25 HIV-1 infected Tunisian patients were collected. Proviral HIV-1 DNA was
      genotyped by sequence analysis of the C2-V3 env region. HIV-1 subtypes were
      determined in 21 DNA sequences: 20 were of subtype B and one was a circulating
      recombinant form (CRF02 AG). Subtype B largely dominates the epidemiology of HIV
      1 infection in Tunisia, suggesting the probable imported origin of HIV-1
      infection, but further studies are needed to investigate the potential
      diversification of HIV-1 isolates in Tunisia.

PMID- 11579284
TI  - A cross-sectional survey of HIV genotype mutations conferring resistance to all
      nonnucleoside reverse transcriptase inhibitors and related features, at the time
      of failure of antiretroviral therapy in the real world.

PMID- 11579285
TI  - Distribution of HIV-1 plasma RNA viral load and CD4 + T-cell counts among HIV
      infected Africans evaluated for antiretroviral therapy.

PMID- 11579286
TI  - Increasing incidence of avascular necrosis of the hip in HIV-infected patients.

PMID- 11579287
TI  - HHV-8 shedding among HIV-infected women.

PMID- 11579288
TI  - Donor and recipient pretransplant conditioning with nonlethal radiation and
      antilymphocyte serum improves the graft survival in a rat small bowel transplant
      model.
AB  - BACKGROUND: Lymphoid tissue within the intestinal graft require immunomodulatory
      strategies to prevent graft versus host disease (GVHD) after transplant. Herein,
      we evaluate the potential advantage of donor-specific bone marrow infusions in
      donor and or recipient preconditioned with total body irradiation and or
      antilymphocyte serum (ALS) on the incidence of GVHD and rejection after small
      bowel transplantation. METHODS: Heterotopic SBTx was performed from DA to Lewis
      rats and distributed in nine groups: control group G0 (n=4) and G1 (n=6) without
      irradiation; recipients in G2 (n=4) were given 400 rd although in groups 3 (n=5),
      G4 (n=6), G6 (n=5), G7 (n=5), and G8 (n=6) with 250 rd. Donors in G5 (n=4) and G6
      were given 250 rd of total body irradiation 2 hours before intestinal retrieval.
      Donors and recipients in G7 and donors in G8 additionally received ALS (day -5).
      G1, 2, 3, 5, 6, 7, and 8 were infused with UDBM and G4 with the same amount of
      TCDBM. Animals received tacrolimus for 15 days and accessed for rejection, GVHD
      and for chimerism analysis. RESULTS: High mortality due to GVHD was observed in
      G2, 3, and 4, and correlated with high levels of donor T cells in recipients
      blood. G0 and G1 showed early acute rejection with progression toward chronic
      rejection, in contrast to the preconditioned groups. High and low doses of total
      body irradiation resulted in allogeneic and in a mixed chimerism, respectively.
      Decrease in donor chimeric cells after 11 weeks in preconditioned groups was
      correlated with severe allograft rejection. CONCLUSION: Donor preconditioning
      with 250 rd and or ALS combined with recipient preconditioning and donor-specific
      bone marrow infusions prevented GVHD and resulted in a transient mixed chimerism
      with inhibition of allograft rejection after small bowel transplantation.

PMID- 11579289
TI  - Fluvastatin in combination with rad significantly reduces graft vascular disease
      in rat cardiac allografts.
AB  - BACKGROUND: RAD is a potent immunosuppressive agent that has been shown to be
      effective in preventing acute and chronic allograft rejection in animal models.
      The HMGCoA reductase inhibitors have been found to reduce the incidence of graft
      vascular disease (GVD) in heart transplant patients and in animal models. This
      study was designed to investigate the effects of fluvastatin or pravastatin in a
      rodent model of GVD produced using low doses of RAD to prevent acute rejection.
      METHODS: Hearts from Fisher 344 rats were heterotopically transplanted to Lewis
      rat recipients. RAD was administered orally at 0.5 mg/kg per day for days 0 to 14
      and then 0.25 mg/kg per day for an additional 85 days to prevent acute rejection
      but allow for the development of GVD. Pravastatin (20 mg/kg per day) or
      fluvastatin (2 or 6 mg/kg per day) was added to the RAD treatment. At the end of
      a 100-day treatment period, the hearts were harvested for morphometric and
      histopathologic examinations. RESULTS: Rats treated with fluvastatin, at either
      dose, had a significant (P< or =0.0239) decrease in coronary arterial intimal
      thickening (GVD) of approximately 43%. Rats treated with pravastatin had a 22%
      reduction in GVD that did not reach statistical significance. Treatment with
      fluvastatin, but not pravastatin, decreased the degree of endomyocardial
      mononuclear cell infiltration seen with RAD administered alone. CONCLUSIONS:
      Fluvastatin significantly decreased GVD in a rat model produced using low-dose
      RAD immunosuppression. To a lesser extent, pravastatin also decreased GVD in this
      model. These data lend further support for the study of fluvastatin, pravastatin,
      and other HMG-CoA reductase inhibitors for the prevention of GVD in cardiac
      transplant patients.

PMID- 11579290
TI  - Rapid rejection of HLA-A2 transgenic skin graft due to indirect allorecognition.
AB  - BACKGROUND: At present, it is not clear whether xenogeneic MHC molecules are
      recognized by T cells directly or indirectly through self-MHC-restricted
      presentation in a transplantation setting. METHODS: We have transplanted skin
      from HLA-A2 transgenic (B6.A2) to nontransgenic C57BL/6 (B6) mice and
      investigated the subsequent mouse T-cell responses to HLA molecules, in vivo and
      in vitro. RESULTS: Skin transplanted from transgenic B6.A2 to B6 mice was
      rejected rapidly, in 12-16 days. Although naive B6 mice did not respond to B6.A2
      splenocytes in vitro, spleen cells from mice that underwent transplantation
      showed strong proliferative responses. An anti-B6.A2 T-cell line from mice that
      underwent transplantation made proliferative responses to B6.A2 splenocytes but
      did not recognize HLA-A2 on human cells or transfected allogeneic mouse cells.
      The indirect, self-H-2-restricted recognition of HLA-A2 implied by this was
      confirmed by the finding that lysates of HLA-A2-positive, but not HLA-A2
      negative, human B cells were stimulatory when pulsed onto syngeneic antigen
      presenting cells and by inhibition of anti-B6.A2 proliferation with both anti
      mouse MHC class I and class II antibodies. CONCLUSION: Our results suggest that
      indirect recognition of xenogeneic MHC antigen plays a predominant role in graft
      rejection.

PMID- 11579291
TI  - Immune cells and immunosuppression in a porcine bronchial model of obliterative
      bronchiolitis.
AB  - BACKGROUND: To study obliterative bronchiolitis (OB), we have developed a porcine
      heterotopic bronchial model. Allografts obliterate within 3 weeks, the
      immunosuppression cyclosporine (CsA)-azathioprine (AZA)-methylprednisolone (MP)
      delays OB, but OB is prevented when AZA is switched to 40-0-(2-hydroxyethyl)
      rapamycin (RAD). To characterize our model, we studied immune cells under various
      immunosuppressive conditions. METHODS: The groups studied were autografts (U),
      allografts (A), and allografts given either CsA-RAD-MP (R), or CsA-AZA-MP (C).
      The implants were harvested at 3, 7, 10, 14, 21, 30, 60, and 90 days after
      transplantation. Epithelial damage and obliteration were graded histologically,
      and the number of CD4, CD8, MHC class II expressing cells, macrophages, and B
      lymphocytes were counted (mean+SEM)/high-power visual field. RESULTS: In group U,
      normal epithelium was regained with no obliteration and only few immune cells. In
      group A, consistent with initially acute ejection, an influx of CD4 (105+23), CD8
      (166+23), and class II (92+20) cells was seen up to day 21, when total
      obliteration preceded by epithelial destruction had already developed. Some
      macrophages were seen and B cells were scarce. In group R, epithelial damage and
      obliteration were insignificant, but moderate numbers of CD4, CD8, and class II
      cells were seen. In group C, epithelial damage and obliteration were only
      delayed, but the immune cell response was clearly blunted. CONCLUSIONS: In our
      model, rejection with significant immune cell influx was still active when
      obliteration was total in nontreated allografts. In immunosuppressed allografts,
      decrease in the number of immune cells alone did prevent OB. These results
      support OB being T-cell mediated. RAD may have additional important effects on
      growth factors and proliferation in prevention of OB.

PMID- 11579292
TI  - Novel approaches to cryopreservation of human pancreatic islets.
AB  - BACKGROUND: Optimized conditions for survival and function of human islets must
      be defined if sufficient islets are to be recovered from a single human donor
      pancreas to reverse type-1 diabetes after isolation, cryopreservation, and
      transplantation. The objective of this study was to compare the cryoprotective
      effect of ethylene glycol (EG) with the standard cryoprotectant, dimethyl
      sulfoxide (DMSO), on isolated human islet survival and function. Furthermore, the
      effect of different addition protocols and equilibrium concentrations of the
      cryoprotectants were studied. METHODS: Islets were isolated from human pancreata
      by using standard techniques of collagenase digestion and discontinuous Ficoll
      gradient purification. Aliquots of freshly isolated human islets were
      cryopreserved in six groups by using DMSO or EG. Cryoprotectants were added
      stepwise to produce a final concentration of 1.5 or 2.0 M, or added in a single
      step to a concentration of 1.5 M. Islets were cryopreserved by using established
      protocols and cultured for 48 hr at 37 degrees C before assessment of percentage
      of recovery and in vitro viability. RESULTS: After cryopreservation, percentage
      of recovery of islets was significantly higher in the group treated with 1.5 M of
      DMSO added in a stepwise protocol (74+/-3%, mean+/-SEM) compared with the
      standard 2.0 M of DMSO (62+/-4%) (P<0.05, unpaired t test, n=6). There was no
      difference between the recovery of islets cryopreserved with either 1.5 M of DMSO
      stepwise (74+/-3%) or 1.5 M of DMSO one-step (69+/-3%). Islet recovery was higher
      in groups treated with DMSO compared with EG, regardless of concentration of
      cryoprotectant or addition protocol, although the difference was significant only
      when comparing DMSO and EG 1.5 M one-step. Furthermore, islets treated with 1.5 M
      of DMSO, added either stepwise (6.0+/-0.4) or in one-step (6.5+/-0.8), had
      significantly higher stimulation indices compared with islets treated with the
      standard cryoprotectant for human islets, 2.0 M of DMSO (4.5+/-0.5) (P<0.05).
      CONCLUSIONS: These results demonstrate that a lower concentration of DMSO (1.5 M)
      allows for the cryopreservation of human islets with superior survival and
      preservation of function post-culture compared with 2.0 M of DMSO and various
      concentrations of EG.

PMID- 11579293
TI  - Patients at risk for development of posttransplant lymphoproliferative disorder:
      plasma versus peripheral blood mononuclear cells as material for quantification
      of Epstein-Barr viral load by using real-time quantitative polymerase chain
      reaction.
AB  - BACKGROUND: Early diagnosis of Epstein-Barr virus (EBV)-associated posttransplant
      lymphoproliferative disorder (PTLD) is required to detect a stage of disease that
      is more likely to respond to treatment. Elevated levels of EBV DNA were found in
      peripheral blood of patients at the onset of PTLD. METHODS: To compare plasma and
      peripheral blood mononuclear cells (PBMCs) as material for real-time quantitative
      polymerase chain reaction (RQ-PCR) measurement of Epstein-Barr viral load, we
      used two sets of primers and probes specific for the BAM HI-K or BAM HI-W region
      of the EBV genome. RESULTS: Patients with PTLD had a median viral load of 19,200
      EBV genomes/microg DNA (n=9) or 3,225 EBV genomes/100 microl plasma (n=5), being
      significantly higher compared with immunosuppressed patients with primary (n=9)
      or reactivated (n=20) EBV infection or immunosuppressed patients without
      serological signs of active EBV infection (n=67) (P<0.001). Hence, a value of
      greater than 5,000 EBV genomes/microg PBMC DNA was considered as a diagnostic
      parameter for PTLD with a sensitivity and specificity of 1.00 or 0.89,
      respectively. When plasma was analyzed, however, a value of greater than 1,000
      EBV genomes/100 microl plasma had both a sensitivity and specificity of 1.00 for
      the diagnosis of PTLD. During remission of PTLD, viral load was more effectively
      cleared in plasma compared with PBMCs. In plasma of nonimmunosuppressed
      individuals, even a qualitative detection of EBV-related sequences was sensitive
      and specific for the diagnosis of primary EBV infection, whereas for analysis of
      PBMC DNA a quantitative parameter had to be considered to differentiate healthy
      individuals (< 100 EBV genomes/microg PBMC DNA) from patients with primary EBV
      infection (>100 EBV genomes/microg PBMC DNA). CONCLUSION: Although both PBMCs and
      plasma were useful as material for EBV-specific RQ-PCR in immunosuppressed
      patients and nonimmunosuppressed individuals, the specificity of analysis seemed
      to be higher if plasma was taken for analysis.

PMID- 11579294
TI  - Posttransplant diabetes mellitus in pediatric renal transplant recipients: a
      report of the North American Pediatric Renal Transplant Cooperative Study
      (NAPRTCS).
AB  - BACKGROUND: The incidence of renal post transplant diabetes mellitus (PTDM) in
      adults varies from 3-46%. METHODS: We did a retrospective analysis of 1365
      children in The North American Pediatric Renal Transplant Cooperative Study with
      renal transplant (Tx) reported between January 92 and July 1997. PTDM, defined as
      >2 weeks of insulin therapy after Tx, developed in 36 patients. A control group
      of 153/1329 non-PTDM patients was selected and matched for age at Tx and primary
      diagnosis. RESULTS: African-Americans were overrepresented (36.1 vs. 17.6%,
      P=0.017) and Hispanics were underrepresented (5.6 vs. 26.1%, P=0.019) among
      cases. Although prednisone dose 30 days post-Tx was higher among cases (0.89
      mg/kg/day) versus controls (0.71 mg/kg/day), P=0.019, cyclosporine dose was
      similar. No differences in prednisone or cyclosporine doses were observed at 6,
      12, or 24 months post-Tx. Tacrolimus use in PTDM group was high (45%). The
      estimated incidence of first acute rejection at 1, 3, and 12 months was higher
      among cases, 0.41+/-0.08, 0.52+/-0.08, 0.61+/-0.08, compared to controls, 0.23+/
      0.02, 0.37+/-0.02, and 47+/-0.02 (P=0.058). Crude graft failure rates of 13.5%
      (5/36) and 12.4% (19/153) were similar between the two groups, so was the
      calculated creatinine clearance at 12 and 24 months and post-Tx hospitalization
      days. CONCLUSION: PTDM occurs in <3% of children. African-Americans are at higher
      risk and Hispanics at lower risk for PTDM. Tacrolimus is a significant risk
      factor for PTDM. Children with PTDM had a higher incidence of acute rejection,
      but graft survival, kidney function, and hospitalization rates were similar to
      selected controls.

PMID- 11579295
TI  - Absorption profiling of cyclosporine microemulsion (neoral) during the first 2
      weeks after renal transplantation.
AB  - BACKGROUND: Evidence suggests that optimal immunosuppressive drug exposure must
      be achieved early posttransplant to minimize the risk of acute graft rejection.
      This study was designed to examine the absorption profile of Neoral during the
      first 2 weeks after renal transplantation, to develop simple sparse-sampling
      pharmacokinetic methods to predict exposure, and to explore the target range for
      optimal clinical immunosuppression under conditions of normal clinical practice.
      METHODS: The prospective multicenter study was conducted in six Canadian renal
      transplant centers in patients receiving Neoral-based immunosuppression. Full (8
      point) pharmacokinetic studies were performed on days 3, 7, and 14 posttransplant
      in a nested subset of patients, and the occurrence and severity of acute
      rejection, infection or other adverse effects, routine laboratory parameters, and
      vital signs were assessed on days 3, 7, 14, and 28. RESULTS: A total of 38 adult
      kidney graft recipients were studied, of whom a nested subset of 16 patients had
      complete 12-hr pharmacokinetic (PK) data on all 3 sampling days. Mean area under
      the time-concentration curve over the entire 12-hr dosage interval (AUC[0-12])
      was 9249+/-3236 microg.hr/L by day 3 and did not change significantly throughout
      the study, although dose-corrected AUC[0-12] rose by 20% from 1924+/-671
      microg.hr/L on day 3 to 2316+/-697 microg.hr/L on day 14 (P=0.067). Mean AUC[0-4]
      was 4566+/-1463 microg.hr/L by day 3 and also did not change significantly,
      although the dose-adjusted AUC[0-4] rose by 31% from 952+/-317 microg.hr/L on day
      3 to 1250+/-697 microg.hr/L on day 14 (P=0.009). AUC[0-4] represented 52% of the
      AUC[0-12] values across the three PK study days and closely predicted this latter
      value (R2=0.803 day 3, R2=0.972 day 14). Cyclosporine (CsA) concentration
      profiles became more uniform throughout the first 14 days posttransplant, with a
      reduction in Tmax from 2.45 to 1.48 hr (P<0.005) and a significant decrease in
      coefficient of variation for AUC[0-12] (35% vs. 21%, P<0.005) and for Tmax (47.4%
      vs. 33.1%, P<0.005). Predosage trough level (C0) was a poor predictor of drug
      exposure, with R2 values less than 0.5 for AUC[0-4] and 0.7 for AUC[0-12] at all
      time points. Sparse sample modeling identified three 3-point sparse-sampling
      strategies that predicted AUC[0-12] and AUC[0-4] with R2 values approaching or
      exceeding 0.9 on all three study days; C2 or C3 seemed to be the most important
      single predictor, with R2 values > 0.80. Ten of the 36 treated patients (27.8%)
      experienced 13 episodes of acute rejection by 28 days posttransplant.
      Longitudinal logistic regression showed no association between C0 and rejection,
      but lower AUC[0-12] values were marginally (P=0.099) and lower AUC[0-4] values
      were significantly (P=0.046) associated with increased risk of rejection. CsA
      exposure on day 7 (n=29) was significantly lower in patients who experienced
      acute rejection in the second week than in those who were rejection free whether
      measured by AUC[0-12] (7976+/-1476 vs. 10,239+/-2759 microg.hr/L; P=0.048), AUC[0
      4] (4027+/-412 vs. 5623+/-1389 microg.hr/L; P<0.0001), C2 (1116+/-183 vs. 1852+/
      522 microg/L; P<0.0001), or Cmax (1415+/-323 vs. 2084+/-450 microg/L; P=0.005),
      and rejection was significantly less common in patients with an AUC[0-4]> 4,500
      microg.hr/L (7% vs. 40%; P=0.041) or a C2 level>1500 microg/L (0% vs. 58%;
      P<0.001) on day 7 (sensitivity, 100%; specificity, 75%; positive predictive
      value, 58%; negative predictive value, 100%). There was no evident relationship
      between CsA exposure and renal toxicity within this patient sample. CONCLUSIONS:
      Absorption of CsA is highly heterogeneous immediately posttransplant, although
      the pharmacokinetic profile normalizes, interpatient variability decreases, and
      CsA absorption increases throughout the first 2 weeks permitting a reduction in
      Neoral dose to achieve constant exposure. Trough (C0) levels do not accurately
      predict CsA exposure or rejection risk and should be replaced by sparse or single
      point (C2) sampling methods, which offer a high predictive value to optimize the
      use of this drug and reduce rejection risk. Acute rejection is significantly more
      common with low CsA exposure during the first week posttransplant, and levels
      above the threshold of approximately AUC[0-4] 4500 microg.hr/L or C2 1500
      microg/L are desirable to minimize the risk of rejection.

PMID- 11579296
TI  - Epidemiology and clinical consequences of vancomycin-resistant enterococci in
      liver transplant patients.
AB  - BACKGROUND: Vancomycin-resistant enterococci (VRE) are increasingly important as
      pathogens in liver transplant patients. To guide control efforts, we conducted an
      epidemiological study of the frequency, source, and modes of transmission of VRE
      at our center. METHODS: During September 1998 through August 1999, we obtained
      weekly surveillance cultures from consenting liver transplant patients and
      surfaces in their rooms. Pooled handwash specimens from personnel also were
      obtained. Specimens were processed on selective media to detect VRE, and isolates
      were typed by pulsed field gel electrophoresis. Information was collected from
      patient records concerning in-hospital treatment and clinical course. RESULTS:
      Serial cultures were obtained during 33 admissions of 29 patients. VRE were
      detected in initial specimens from 6 admissions, and nosocomial acquisition of
      VRE occurred in 12 (44%) of the remaining 27 admissions. Seven different strain
      types of VRE were detected. The initial site of acquisition was stool in all
      cases; bile became culture-positive in only two patients. Overall, 16 (55%) of
      the 29 patients became colonized, usually after transplantation. VRE were
      detected in environmental cultures during 10 admissions and in 2 of 21 pooled
      handwashes. No statistically significant differences in clinical status or
      treatment were found when colonized patients were compared to noncolonized
      controls. The only VRE infection resulted from a choledochojejunostomy
      anastomotic leak. CONCLUSION: Alimentary tract colonization by VRE occurred
      commonly in liver transplant patients, probably by cross-transmission. The
      clinical consequences were modest in the patients studied, but colonized
      transplant patients provide a substantial reservoir for continued VRE
      transmission in hospitals.

PMID- 11579297
TI  - ABO-incompatible living-donor kidney transplantation in children.
AB  - BACKGROUND: Due to a severe shortage of suitable cadaveric allografts for
      children awaiting kidney transplants, we have performed a series of ABO
      incompatible living kidney transplantations (LKT) at our institution. METHODS:
      Between July 1989 and March 2000, 16 pediatric patients (3 female, 13 male)
      underwent ABO-incompatible LKT. The mean age at transplantation was 10.9+/-4.3
      years (range 5.1-15.0 years). The donor to recipient ABO blood antigen
      incompatibility was as follows: A1-->O, 5 patients; B-->O, 6 patients; A1B-->B, 2
      patients; and A1B -->B, A1-->B, or B-->A1, 1 patient each. The median
      pretransplantation anti-A1 titers of eight A-incompatible recipients were 1:128
      (IgM, range 1:16 to 1:512) and 1:32 (IgG, range 1:2 to 1:128). Median anti-B
      titers of seven B-incompatible recipients were 1:32 (IgM, range 1:4 to 1:128) and
      1:8 (IgG, range 1:2 to 1:64). All patients received three or four sessions of
      plasmapheresis (PP) and/or immunoadsorption (IA) to remove the anti-A and/or anti
      B antibodies before transplantation. Immunosuppression initially consisted of
      cyclosporine, methylprednisolone, cyclophosphamide, and antilymphocyte globulin.
      Splenectomy was performed on all recipients at the time of transplantation.
      RESULTS: The patients were followed for 6 to 122 months with a mean follow-up of
      63 months. All 16 recipients who underwent ABO-incompatible LKT achieved a
      pretransplant isoagglutinin titer less than 1:8 with 3-4 sessions of PP/IA
      treatment. Of 16 patients, 10 patients had rebound increase in their IgM and/or
      IgG anti-A/B titers to greater than 1:64 or predepletion levels within 10 days
      posttransplantation. In addition, nine patients developed renal dysfunction in
      association with the rebound increase in their anti-A/B. One patient lost his
      graft because of uncontrolled delayed hyperacute rejection, whereas eight other
      recipients recovered completely with pulse steroids and PP/IA therapy. After the
      third week posttransplant, there was no correlation between the occurrence of AR
      and their isoagglutinin titers. Moreover, no antibody-mediated rejection was
      observed, even in recipients with continued high titer anti-A and/or anti-B
      antibodies. Patient survival is 100% to date. The actuarial 1-year and 5-year
      graft survival rates are 87% and 85%, respectively. No fatal infectious
      complications occurred despite the combination of splenectomy and
      immunosuppressive drugs. CONCLUSIONS: We have demonstrated that with adequate pre
      and posttransplant management, successful kidney transplantation across the ABO
      barrier is possible in the pediatric population. "Accommodation" of the
      allografts occurred within 2 weeks of transplantation. Subsequently, the long
      term graft outcome of ABO-incompatible LKT was comparable to that of ABO
      compatible LKT.

PMID- 11579298
TI  - Impact of cardiac transplantation on molecular pathology of ET-1, VEGF-C, and
      mitochondrial metabolism and morphology in dilated versus ischemic
      cardiomyopathic patients.
AB  - Little is known about the long-term impact of cardiac transplantation on activity
      and modifications of endothelin (ET)-1 system, vascular endothelial growth factor
      (VEGF), and mitochondrial metabolism and morphology in patients with ischemic
      cardiomyopathy (ICM) versus dilated cardiomyopathy (DCM). Messenger RNA (mRNA)
      expression levels of ET-1, endothelin converting enzyme (ECE)-1, VEGF-C,
      carnitine palmitoyltransferase (CPT)-1, and carnitine acetyltransferase (CARAT),
      as well as the number of normal, edematous, and degenerated mitochondria were
      assessed in left ventricular biopsies of 21 patients with DCM and 20 with ICM
      (New York Heart Association class III-IV) before and up to 3 months after cardiac
      transplantation. Cardiac samples of donated, nonfailing hearts served as controls
      (n=10). In cardiac biopsies of both ICM and DCM patients, ET-1, VEGF-C, CPT-1,
      and CARAT mRNA were up-regulated, whereas ECE-1 mRNA was down-regulated (P<0.05).
      Degenerated mitochondria had the highest number in both groups, followed by
      normal and edematous mitochondria. After cardiac transplantation, in ICM patients
      impaired gene expression levels decreased to, or below, normal levels, and the
      number of normal mitochondria increased (P<0.05). In implanted hearts of DCM
      patients, however, up-regulated ET-1 transcript levels persisted and the number
      of normal mitochondria decreased, whereas the number of degenerated mitochondria
      increased (P<0.05), and edematous mitochondria remained unchanged in number.
      These results show that cardiac transplantation corrects the impaired hemodynamic
      and echocardiographic parameters in both groups, whereas in DCM, the molecular
      pathology of ET-1 system and mitochondria persists. Therefore, it is more likely
      that these changes are the cause rather than a consequence of DCM.

PMID- 11579299
TI  - Induction versus noninduction in renal transplant recipients with tacrolimus
      based immunosuppression.
AB  - BACKGROUND: The aim of this study was to compare the efficacy and safety of
      induction treatment with antithymocyte globulins (ATG) followed by tacrolimus
      therapy with immediate tacrolimus therapy in renal transplant recipients.
      METHODS: This 12-month, open, prospective study was conducted in 15 centers in
      France and 1 center in Belgium; 309 patients were randomized to receive either
      induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9
      or immediate tacrolimus-based triple therapy (n=158). In both study arms, the
      initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the
      first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was
      administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute
      rejections were reported for 15.2% (induction) and 30.4% (noninduction) of
      patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9%
      (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections
      were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total
      of nine patients died. Patient survival and graft survival at month 12 was
      similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%,
      respectively). Statistically significant differences in the incidence of adverse
      events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs.
      noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2%
      vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and
      thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum
      sickness was observed in 10.6% of patients. The incidence of new onset diabetes
      mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences
      of acute rejection were found in both treatment arms. Induction treatment with
      ATG has the advantage of a lower incidence of acute rejection, but it
      significantly increases adverse events, particularly CMV infection.

PMID- 11579300
TI  - Population pharmacokinetics of tacrolimus in children who receive cut-down or
      full liver transplants.
AB  - BACKGROUND: The aim of this study was to investigate the population
      pharmacokinetics of tacrolimus in pediatric liver transplant recipients and to
      identify factors that may explain pharmacokinetic variability. METHODS: Data were
      collected retrospectively from 35 children who received oral immunosuppressant
      therapy with tacrolimus. Maximum likelihood estimates were sought for the typical
      values of apparent clearance (CL/F) and apparent volume of distribution (V/F)
      with the program NONMEM. Factors screened for influence on the pharmacokinetic
      parameters were weight, age, gender, postoperative day, days since commencing
      tacrolimus therapy, transplant type (whole child liver or cut-down adult liver),
      liver function tests (bilirubin, alkaline phosphatase [ALP], aspartate
      aminotransferase [AST], gamma-glutamyl transferase [GGT], alanine
      aminotransferase [ALT]), creatinine clearance, hematocrit, corticosteroid dose,
      and concurrent therapy with metabolic inducers and inhibitors of tacrolimus.
      RESULTS: No clear correlation existed between tacrolimus dosage and blood
      concentrations (r2=0.003). Transplant type, age, and liver function test values
      were the most important factors (P<0.01) that influenced the pharmacokinetics of
      tacrolimus. CL/F estimates were greater in whole liver recipients, decreased with
      increasing patient age and AST values, and increased with increasing GGT values.
      Average parameter estimates were CL/F=5.75 L/h (cut-down liver), CL/F=44 L/h
      (whole liver), and V/F=617 L. Marked intersubject variability (CV%=110% to 297%)
      and residual variability (CV%=42%) was observed. CONCLUSIONS: Pharmacokinetic
      information obtained in this study may assist physicians in making individualized
      dosage decisions in regard to tacrolimus in pediatric liver transplant
      recipients. Children who received a whole child's liver appeared to retain
      "pediatric" clearance, whereas those who received a cut-down adult liver had
      "adult" clearances (on average 7-fold less).

PMID- 11579301
TI  - Conversion from cyclosporine to FK506 in adult liver transplant recipients: a
      combined North American and European experience.
AB  - BACKGROUND: Although cyclosporine (CsA) made clinical liver transplantation
      possible, side effects and development of rejection have limited its use. In some
      patients, conversion to tacrolimus has been necessary to abrogate side effects
      and to preserve allograft function. METHODS: The results of conversion from CsA
      to tacrolimus were studied retrospectively in 94 liver allograft recipients from
      a North American and a European transplant center (Duke University Medical
      Center, Durham, NC, and Hopital Beaujon, Clichy, France). RESULTS: Forty-seven of
      94 patients (50%) were converted for steroid-resistant acute rejection.
      Conversion was successful in 91% of these patients, whereas 9% of patients
      developed chronic rejection. A further nine patients were converted for chronic
      allograft rejection with positive results in eight of nine grafts. Mean serum
      bilirubin in these nine patients was 8.7 mg/dl before conversion and 2.1 mg/dl 6
      months after conversion (P=0.02). Nine patients were converted due to inability
      to wean steroid. Of these, six patients remains steroid free 1 year after
      conversion. Twenty-three patients (24%) were converted for nephrotoxicity with a
      reduction in serum creatinine from 167+/-36 mmol/L to 119+/-28 mmol/L 1 year
      after conversion (P=0.006). Eight of 11 patients converted for neurotoxicity
      improved after conversion. Conversion to tacrolimus had no effect on seizure
      frequency or memory loss. CONCLUSIONS: These results suggest that conversion to
      tacrolimus from CsA is an appropriate paradigm for graft rescue and treatment of
      a variety of side effects after liver transplant. However, some situations such
      as memory loss and hypertension may require other strategies.

PMID- 11579302
TI  - Posttransplant diabetes mellitus in liver transplant recipients: risk factors,
      temporal relationship with hepatitis C virus allograft hepatitis, and impact on
      mortality.
AB  - BACKGROUND: Recent studies suggest an association between diabetes mellitus and
      hepatitis C virus (HCV) infection. Our aim was to determine (1) the prevalence
      and determinants of new onset posttransplant diabetes mellitus (PTDM) in HCV (+)
      liver transplant (OLT) recipients, (2) the temporal relationship between
      recurrent allograft hepatitis and the onset of PTDM, and (3) the effects of
      antiviral therapy on glycemic control. METHODS: Between January of 1991 and
      December of 1998, of 185 OLTs performed in 176 adult patients, 47 HCV (+) cases
      and 111 HCV (-) controls were analyzed. We reviewed and analyzed the
      demographics, etiology of liver failure, pretransplant alcohol abuse, prevalence
      of diabetes mellitus, and clinical characteristics of both groups. In HCV (+)
      patients, the development of recurrent allograft hepatitis and its therapy were
      also studied in detail. RESULTS: The prevalence of pretransplant diabetes was
      similar in the two groups, whereas the prevalence of PTDM was significantly
      higher in HCV (+) than in HCV (-) patients (64% vs. 28%, P=0.0001). By
      multivariate analysis, HCV infection (hazard ratio 2.5, P=0.001) and
      methylprednisolone boluses (hazard ratio 1.09 per bolus, P=0.02) were found to be
      independent risk factors for the development of PTDM. Development of PTDM was
      found to be an independent risk factor for mortality (hazard ratio 3.67,
      P<0.0001). The cumulative mortality in HCV (+) PTDM (+) versus HCV (+) PTDM (-)
      patients was 56% vs. 14% (P=0.001). In HCV (+) patients with PTDM, we could
      identify two groups based on the temporal relationship between the allograft
      hepatitis and the onset of PTDM: 13 patients developed PTDM either before or in
      the absence of hepatitis (group A), and 12 concurrently with the diagnosis of
      hepatitis (group B). In gr. B, 11 of 12 patients received antiviral therapy.
      Normalization of liver function tests with improvement in viremia was achieved in
      4 of 11 patients, who also demonstrated a marked improvement in their glycemic
      control. CONCLUSION: We found a high prevalence of PTDM in HCV (+) recipients.
      PTDM after OLT was associated with significantly increased mortality. HCV
      infection and methylprednisolone boluses were found to be independent risk
      factors for the development of PTDM. In approximately half of the HCV (+)
      patients with PTDM, the onset of PTDM was related to the recurrence of allograft
      hepatitis. Improvement in glycemic control was achieved in the patients who
      responded to antiviral therapy.

PMID- 11579303
TI  - Hypercoagulable states in renal transplant candidates: impact of anticoagulation
      upon incidence of renal allograft thrombosis.
AB  - INTRODUCTION: Although multiple studies of demographic variables have been
      associated with allograft thrombosis, these results are not routinely
      reproducible. Are ESRD patients with hypercoagulable states (HCS) (antithrombin
      III deficiency, protein S or C deficiency, activated protein C resistance, and
      anticardiolipin antibodies) at predictably greater risk for allograft thrombosis?
      METHODS: Between 1996 and 1999, all renal transplant candidates were screened for
      hypercoagulability risk factors [HRF] (multiple arteriovenous access thromboses,
      prior deep vein thrombosis, prior allograft thrombosis, collagen vascular
      disease, multiple miscarriages, diabetes, autoimmune disease, and Fabry's
      disease). HRF(+) candidates were then tested for HCS status. We administered
      preemptive posttransplant i.v. Heparin in HCS(+) patients and observed the impact
      of this intervention upon the incidence of allograft thrombosis. We compared
      demographic data and incidence of allograft thrombosis in an historic control
      (346 patients transplanted between June 31, 1992, and March 5, 1996) not tested
      for HCS and a study cohort (502 patients transplanted between March 6, 1996, and
      June 31, 1999) prospectively screened for HRF. HRF(+) patients who were HCS(+) in
      the study cohort received i.v. heparin immediately after transplant and p.o.
      warfarin as outpatients. RESULTS: Demographic characteristics previously
      implicated in allograft thrombosis were equivalently distributed in both cohorts
      with the exceptions that more living-donor transplants (33.1% vs. 15.3%) were
      performed in study cohort, CIT>24 hr occurred in more control patients (37.3% vs.
      22.1%) and more study patients (16.7% vs. 0%) received tacrolimus.
      Hypercoagulable states were found upon reevaluating five of seven controls
      (71.4%), who lost prior allografts to thrombosis. Hypercoagulable states were
      prospectively detected in 10 study patients with hypercoagulability risk factors.
      Most (9 of 10) study patients receiving anticoagulation have achieved long-term
      allograft function. Study group allograft thrombosis incidence was reduced (1.59%
      vs. 4.05%). Hypercoagulable states were demonstrated in most episodes of
      allograft thrombosis. Control patients who lost prior allografts to thrombosis
      were anticoagulated after retransplantation and 100% achieved long-term allograft
      function. CONCLUSIONS: Long-term allograft function has been achieved in 90% of
      study patients when prophylactically anticoagulating study patients with
      hypercoagulable states. A 2.6-fold reduction in the expected incidence of
      allograft thrombosis was observed in anticoagulated patients with hypercoagulable
      states.

PMID- 11579304
TI  - Generation of autologous Epstein-Barr virus-specific cytotoxic T cells for
      adoptive immunotherapy in solid organ transplant recipients.
AB  - BACKGROUND: Epstein-Barr virus (EBV)-driven posttransplant lymphoproliferative
      disorders (PTLD) affect 2%-27% of solid organ transplant (SOT) recipients.
      Adoptive immunotherapy may have therapeutic potential in this setting, but there
      is little experience in generating autologous EBV-specific cytotoxic T-cell
      lymphocytes (EBV-CTLs) from SOT recipients, and their efficacy and persistence in
      an immunosuppressed environment is unknown. METHODS: EBV-CTLs were generated from
      eight SOT recipients, using weekly stimulations with autologous lymphoblastoid
      cell lines (LCLs) and interleukin-2. CTL phenotype and function were evaluated in
      the presence of therapeutic concentration of cyclosporin A or FK506. RESULTS: In
      all cases, CTLs expanded with normal kinetics. The majority was CD3+CD8+ (mean,
      76%), with less than 3% of natural killer cells. All ex vivo-generated CTLs
      produced significantly higher killing of autologous LCLs than of HLA-mismatched
      LCLs (mean, 56% vs. 14% at 20:1 ratio). No lysis of autologous or allogeneic PHA
      blasts was observed. The CTL expansion rate was reduced in a concentration
      dependent manner in the presence of immunosuppressive drugs; however, neither
      lytic activity nor phenotype was affected. CONCLUSIONS: Using methods that are
      approved for clinical application, EBV-CTLs can be generated from SOT recipients,
      even those with frank lymphoma, or who are receiving immunosuppressive drugs.
      These CTLs retain their function in the presence of immunosuppressive agents.
      Although in vivo efficacy, safety, and persistence can be assessed only in
      clinical trials, our results suggest that CTLs can be effective for the treatment
      of PTLD, even when immunosuppression cannot be reduced because of the high risk
      of graft rejection.

PMID- 11579305
TI  - Living-related liver transplantation for primary biliary cirrhosis.
AB  - BACKGROUND: The prognosis of patients with primary biliary cirrhosis has improved
      since the introduction of transplantation. However, there has been limited
      experience with living-related liver transplantation for primary biliary
      cirrhosis. PATIENTS AND METHODS: Between January 1996 and October 2000, 105
      patients underwent living-related liver transplantation at the University of
      Tokyo Hospital. Eighteen of these patients with primary biliary cirrhosis were
      the subjects of this study. The risk scores in the conventional and updated Mayo
      models ranged from 5.9 to 11.6 and 6.9 to 13.7, respectively. RESULTS: The graft
      weight ranged from 330 to 533 g, corresponding to 33 to 55% of the recipient's
      standard liver volume. Two patients died of pneumonia, 1 died due to sepsis, and
      the remaining 15 patients survived. The risk scores for the conventional and
      updated Mayo models correlated well with the duration of hospitalization (P=0.01,
      R=0.67 for both). The scores of the dead patients by the two models were more
      than 10 and 12, respectively. The postoperative courses of all of the donors were
      uneventful. CONCLUSIONS: The risk score in the Mayo model adequately reflected
      the outcome of the patients. To achieve the best possible outcome, further
      therapeutic tactics are necessary for patients with conventional or updated Mayo
      risk scores of more than 10 or 12, respectively.

PMID- 11579306
TI  - A prospective randomized trial of tacrolimus and prednisone versus tacrolimus,
      prednisone and mycophenolate mofetil in primary adult liver transplantation: a
      single center report.
AB  - BACKGROUND: Tacrolimus (TAC) and mycophenolate mofetil (MMF) are currently
      approved immunosuppressants for prevention of rejection in liver transplantation
      (LTx). They have different modes of action and toxicity profiles, but the
      efficacy and safety of MMF in primary liver transplantation with TAC has not been
      determined. METHODS: An Institutional Review Board-approved, open-label, single
      center, prospective randomized trial was initiated to study the efficacy and
      toxicity of TAC and steroids (double-drug therapy (D)) versus TAC, steroids, and
      MMF (triple-drug therapy (T)) in primary adult LTx recipients. Both groups of
      patients were started on the same doses of TAC and steroids. Patients randomized
      to T also received 1 gm MMF twice a day. RESULTS: Between August 1995 and May
      1998, 350 patients were enrolled at a single center-175 in the D and 175 in the T
      groups. All patients were followed until May 1998, with a mean follow-up of
      33.8+/-9.1 months. Using an intention-to-treat analysis, the 1-, 2-, 3-, and 4
      year patient survival was 85.1%, 81.6%, 78.6%, and 75.8%, respectively, for D and
      87.4%, 85.4%, 81.3%, and 79.9%, respectively, for T. The 4-year graft survival
      was 70% for D and 72.1% for T. Although the rate of acute rejection in the first
      3 months was significantly lower for T than for D (28% for triple vs. 38.9% for
      double, P=0.03), the overall rate of rejection for T at the end of 1 year was not
      significantly lower than for the D (38.9% triple vs. 45.2% double). The median
      time to the first episode of rejection was 14 days for D versus 24 days for T
      (P=0.008). During the study period, 38 of 175 patients in D received MMF to
      control ongoing acute rejection, nephrotoxicity, and/or neurotoxicity. On the
      other hand, 103 patients in the T discontinued MMF for infection,
      myelosuppression, and/or gastrointestinal disturbances. The need for
      corticosteroids was less after 6 months for T and the perioperative need for
      dialysis was lower with use of MMF. CONCLUSION: This final report confirms
      similar patient survival and graft survival up to 4 years with a trend towards
      fewer episodes of rejection, lower need for steroids, and better perioperative
      renal function. However, the complex nature of LTx patients and their
      posttransplantation course prevents the routine application of MMF.

PMID- 11579307
TI  - Risk factors for chronic rejection after pediatric liver transplantation.
AB  - BACKGROUND: Chronic rejection is a major cause of graft failure and a frequent
      reason for retransplantation after pediatric liver transplantation.
      Identification of risk factors for chronic rejection in pediatric transplant
      recipients is vital to understanding the pathogenesis of chronic rejection and
      may help prevent further graft loss. METHODS: The study population consisted of
      285 children with 385 liver transplants performed at University of Chicago
      between 1991 and 1999. Logistic regression analysis was used to evaluate risk
      factors for chronic rejection, including age, sex, race, type of graft (living
      related vs. cadaveric), native liver disease, acute rejection episodes,
      cytomegalovirus (CMV) infection, and posttransplant lymphoproliferative disease
      (PTLD). RESULTS: The chronic rejection rate was significantly lower in recipients
      of living-related grafts than in recipients of cadaveric grafts (4% vs. 16%,
      P=0.001). African-American recipients had a significantly higher rate of chronic
      rejection than did Caucasian recipients (26% vs. 8%, P<0.001). Numbers of acute
      rejection episodes, transplantation for autoimmune disease, occurrence of PTLD,
      and CMV infection were also significant risk factors for chronic rejection.
      However, recipient age, gender, donor-recipient gender mismatch, and donor
      recipient ethnicity mismatch were not associated with higher incidence of chronic
      rejection CONCLUSION: We have identified a number of risk factors for chronic
      rejection in a large group of pediatric liver allograft recipients. We believe
      that donor-recipient matching for gender or race is not likely to reduce the
      incidence of chronic rejection. The elucidation of the mechanisms by which living
      related liver transplantation affords protection against chronic rejection may
      provide insight into the immunogenetics of chronic rejection and help prevent
      further graft loss.

PMID- 11579308
TI  - Restored hypoglycemic counterregulation is stable in successful pancreas
      transplant recipients for up to 19 years after transplantation.
AB  - BACKGROUND: Pancreas transplantation has been shown to fully restore glucagon
      response and partially restore epinephrine response to hypoglycemia during the
      first few years after transplantation in patients with type 1 diabetes. However,
      prior studies have not examined hypoglycemic counterregulation in any pancreas
      transplant recipient of more than 6 years' duration. METHODS: To determine
      whether restoration of hypoglycemic counterregulation is maintained over a
      prolonged period after transplantation, we studied counterregulatory responses
      and symptom recognition in two groups of pancreas transplant recipients using a
      stepped hypoglycemic, hyperinsulinemic clamp. Group 1 consisted of 11 successful
      transplant recipients of 11 to 19 years' duration (mean+/-SE, 13.9+/-0.7 years).
      Group 2A consisted of seven successful pancreas transplant recipients of 5 to 11
      years' duration (mean+/-SE, 8.7+/-0.9 years) who had been studied approximately 5
      years earlier using the same stepped, hypoglycemic clamp technique. RESULTS: Both
      groups had significant rises in plasma glucagon during the hypoglycemic clamp
      similar to that seen in short-term recipients and normal controls. Both groups
      also had significant increases in plasma epinephrine responses similar to that
      seen in short-term transplant recipients but less than that of normal control
      subjects. The mean symptom scores of group 1 were significantly less than those
      of the control group at glucose levels of 60 and 50 mg/dL but not at 40 mg/dL.
      The mean symptom scores of group 2A were not significantly different than that of
      control subjects. CONCLUSION: These results indicate that the restoration of
      hypoglycemic counterregulation by pancreas transplantation remains stable in
      successful pancreas transplant recipients for up to 19 years after
      transplantation.

PMID- 11579309
TI  - The use of liver grafts from donors with bacterial meningitis.
AB  - BACKGROUND: The shortage of suitable donors for transplantation is a worldwide
      problem. The use of cadaveric donors with bacterial meningitis may be associated
      with an increased risk of sepsis. We report the results of orthotopic liver
      transplantation (OLT) from 33 such donors between 1989 and 1999. METHODS: The
      hospital records of recipients from cadaveric donors with meningitis (study
      group) were retrospectively reviewed and compared with matched recipients from
      cadaveric donors dying from causes other than meningitis (recipient-matched
      control group). RESULTS: A total of 34 recipients underwent 21 whole, 10 reduced,
      and 3 split liver transplants from 33 cadaveric donor livers with bacterial
      meningitis. The donor meningitis pathogens were Neisseria meningitidis (n=14),
      Streptococcus pneumoniae (n=4), Haemophilus influenzae (n=1), Streptococcus
      species (n=2), and unknown (n=12). Twenty-seven patients had an elective OLT and
      seven patients had an emergency OLT. Adequate antimicrobial therapy before organ
      procurement and after transplant was administrated. The mean posttransplant
      follow-up was 37 months (range: 1 day-106 months). There was no difference in
      recipient and graft survival rates between the study and the recipient-matched
      groups. In the study group, there were no infectious complications caused by the
      meningeal pathogens. Overall patient survival rates were 79%, 76%, 72%, and 72%
      at 1, 6, 12, and 60 months, respectively. Graft survival was 77%, 70%, 65%, and
      65% at 1, 6, 12, and 60 months, respectively. The survival rate in elective cases
      was significantly better than emergency cases (P<0.05). CONCLUSION: Liver
      transplantation from donors with bacterial meningitis is a safe procedure
      provided both donors and recipients receive adequate antimicrobial therapy.

PMID- 11579310
TI  - Preoperative factors associated with outcome and their impact on resource use in
      1148 consecutive primary liver transplants.
AB  - BACKGROUND: Hepatic transplantation is a highly effective but costly treatment
      for end-stage hepatic dysfunction. One approach to improve efficiency in the use
      of scarce organs for transplantation is to identify preoperative factors that are
      associated with poor outcome posttransplantation. This may assist both in
      selecting patients optimal for transplantation and in identifying strategies to
      improve survival. METHODS: In the present work, we retrospectively reviewed
      consecutive liver transplants performed at the University of California at Los
      Angeles during a 6-year period and determined preoperative variables that were
      associated with outcome in primary grafts. In addition, we used the hospital's
      cost accounting database to determine the impact of these variables on the degree
      of resource use by high-risk patients. RESULTS: We found five variables to have
      independent prognostic value in predicting graft survival after primary liver
      transplantation: (1) donor age, (2) recipient age, (3) donor sodium, (4)
      recipient creatinine, and (5) recipient ventilator requirement pretransplant.
      Recipient ventilator requirement and elevated creatinine were associated with
      significant increases in resource use during the transplant admission.
      CONCLUSIONS: Patients at high risk for graft failure and costly transplants can
      be identified preoperatively by a set of parameters that are readily available,
      noninvasive, and inexpensive. Selection of recipients on the basis of these data
      would improve the efficiency of liver transplantation and reduce its cost.

PMID- 11579311
TI  - Clinical and subclinical acute rejection early after liver transplantation:
      contributing factors and relevance for the long-term course.
AB  - Routine transplant aspiration cytology (TAC) after liver transplantation gives
      detailed information that concerns immunologic events in the graft. TAC can be
      helpful for diagnosis of acute rejection, but it also detects morphological signs
      of rejection without clinical correlate ("subclinical rejection"). The aim of
      this study was to systematically evaluate factors that influence the development
      of early clinical and subclinical rejection and to analyze the relevance of these
      early immunologic processes for the long-term course. The study includes the
      course of 340 patients after liver transplantation between 1988 and 1995 in whom
      TAC was performed routinely and who were followed for a minimum of 3 years. TAC
      findings were correlated with the following various clinical parameters: (1)
      Overall early clinical rejection occurred in 17.4%, subclinical rejection in
      59.1%, and no immune activation was seen in 23.5% of patients. (2) Incidence of
      early clinical and subclinical rejection was markedly influenced by type of
      immunosuppression. (3) Basic disease and extent of preservation injury had only a
      minor influence; there was a trend towards lower early rejection associated with
      more severe preservation damage, increased patient age, and early
      retransplantation. (4) Presence of early clinical or subclinical rejection was
      not associated with a higher incidence of chronic dysfunction. (5) Falsely
      indicated antirejection treatment was associated with inferior graft survival.
      Subclinical rejection is very frequent early after liver transplantation,
      requires no treatment, and has no long-term adverse effect. Incidence of early
      clinical rejection is mainly determined by initial immunosuppression; its
      occurrence has no negative long-term effects and may even be associated with a
      lower risk for later immunological complications. Thus, the incidence of early
      acute rejection is no adequate parameter for evaluating the quality of an
      immunosuppressive treatment protocol.

PMID- 11579312
TI  - Coadministration of either cyclosporine or steroids with humanized monoclonal
      antibodies against CD80 and CD86 successfully prolong allograft survival after
      life supporting renal transplantation in cynomolgus monkeys.
AB  - BACKGROUND: Recent studies have shown some efficacy using monotherapy with
      monoclonal antibodies (mAb) against CD80 and CD86 receptors after life-supporting
      renal transplantation in non-human primates. Our study was designed to evaluate
      the efficacy of combinations of the same mAbs with either microemulsion
      cyclosporine (CsA) or steroids. METHODS: Unilateral renal transplantation was
      performed in 16 blood group-matched and MLR-mismatched cynomolgus monkeys that
      were assigned to four different treatment groups. All monkeys in groups I, II,
      and IV were treated with the combination of a CD80 (h1F1) and CD86 (h3D1) mAb
      given at 20 mg/kg each preoperatively, then 5 mg/kg at weekly intervals starting
      postoperative (po) day 0 until poday 56 (9 doses). In group I the animals (n=4)
      were treated with mAbs only. In group II (n=4) mAbs were combined with a CsA
      regimen adjusted daily to maintain target 24 hr trough levels of 150-300 ng/ml
      CsA for poday 0 to poday 56. In group III (n=4) the animals received CsA
      monotherapy according to the same regimen as group II. In group IV
      methylprednisone was administered at 2 mg/kg IV on poday 0-2, then at 0.5
      mg/kg/day prednisone per gavage that was and tapered to 0.2 mg/kg/day on which
      they were maintained until poday 56. All animals were off all immunosuppressive
      treatment after poday 56 and were then followed until poday 119. RESULTS: The
      mean survival of groups I-IV was 74 (range 9-119 days), 113 (96-119 days), 39 (22
      71 days), and 79 days (6 to 119), respectively. All animals in group I showed
      clinical evidence of acute severe rejection (fever, creatinine increase, anuria)
      within the first week posttransplant, including those that retained renal
      function until poday 119. Only one animal in group II had a moderate clinical
      rejection during the treatment period and three of four animals survived the
      intended follow-up period. All animals in group III had multiple biopsy proven or
      severe clinical rejection episodes within the first 21 days and only one animal
      survived beyond poday 40. Moderate or severe acute rejection was diagnosed in
      three of four animals of group IV within the first 28 days post transplant and
      only one animal survived until poday 119. CONCLUSION: Our data show that
      combining a calcineurin inhibitor or prednisone with mAbs designed to block
      costimulatory signals does not antagonize the immunosuppressive efficacy of these
      mAbs. In addition, combining CsA with mAbs directed against the CD80 and CD86
      receptors significantly prolongs graft survival when compared to CsA monotherapy.
      Therefore clinical trials of humanized mAbs to CD80 and CD86 used in combination
      with conventional immunosuppression can be considered.

PMID- 11579313
TI  - Histological alterations in implant and one-year protocol biopsy specimens of
      renal allografts.
AB  - BACKGROUND: The natural course of histological changes and their correlations
      with clinical parameters have not been studied in large numbers in renal
      allograft specimens. The aim of this study was to determine whether any
      histological alterations developed during the first posttransplantation year.
      Immunological and nonimmunological factors possibly associated with subsequent
      histopathological changes and development of chronic rejection were also
      assessed. METHODS: We studied 102 cadaveric kidney allografts for which both
      implant and 1-year protocol biopsy specimens were available. The chronic
      allograft damage index (CADI) was used to quantify the extent of histological
      changes that developed during the first year. RESULTS: Overall, an increase in
      histological alterations were seen during the first posttransplantation year, and
      the CADI increased significantly. The mean CADI was 0.7 in relation to implant
      biopsy samples and 2.9 in relation to 1-year biopsy samples (P<0.05). Although
      the degree of changes increased during the first posttransplantation year, they
      were seldom severe. Significant increases in incidences of interstitial
      inflammation and fibrosis, tubular atrophy, and basement-membrane thickening were
      seen. Vascular intimal proliferation and glomerular mesangial matrix increase and
      glomerular sclerosis were also noted. In contrast, anisometric vacuolization in
      the tubular epithelium decreased significantly in incidence during the first
      year. CADI values 1 year after transplantation were significantly affected by
      donor age, occurrence of acute rejection episodes, and prevalence of HLA-DR
      mismatches. CADIs were also significantly higher in grafts with decreased
      function. CONCLUSIONS: Histopathological alterations increased in almost every
      graft, even well-functioning grafts, during the first year. The CADIs relating to
      alterations seen in cases of chronic rejection increased significantly and were
      strongly affected by both immunological and nonimmunological factors.

PMID- 11579314
TI  - New method for thyroid transplantation across major histocompatibility complex
      barriers using allogeneic bone marrow transplantation.
AB  - BACKGROUND: It has been shown that allogeneic bone marrow transplantation (BMT)
      after lethal irradiation elicits donor-specific tolerance for organ or tissue
      transplantation across major histocompatibility complex (MHC) barriers. Recently,
      we have demonstrated that the portal venous (p.v.) administration of donor bone
      marrow cells (BMCs) elicits donor-specific tolerance across MHC barriers by only
      two administrations of an immunosuppressant (CsA or FK-506). In our study, using
      the central and intrahepatic tolerance-inducing system, we have established a new
      method for thyroid transplantation with BMT that would be more applicable to
      humans. METHODS: In addition to sublethal (6-5 Gy) irradiation, recipient B6 (H
      2b) mice received injections i.p. with the myeloablative drug busulfan (BU) on
      day -2 to provide a sufficient "space" for the donor hematopoietic cells to
      expand in the recipients. To induce the intrahepatic tolerance, donor BALB/c (H
      2d) BMCs were treated with neuraminidase (Neu), which enhances the trapping of
      i.v. injected BMCs in the liver. After the injection of Neu-treated BMCs, the
      thyroid organs from the BALB/c mice were engrafted under the renal capsules.
      RESULTS: A 90% graft survival rate was obtained over 100 days by a combination of
      BU administration, 6 Gy irradiation, and i.v. injection of Neu-treated BMCs [BU+6
      Gy+(Neu) i.v.], and a 70% graft survival rate was obtained by [BU+5 Gy+(Neu)
      i.v.]. However, the graft survival rate significantly decreased when either the
      BU or Neu treatment was omitted. T cells collected from the tolerant recipients
      suppressed the proliferative responses to donor alloantigens. CONCLUSIONS: Using
      both BU and Neu treatments, we have succeeded in inducing long-term tolerance and
      preventing the rejection of thyroid allografts by the single-day protocol.

PMID- 11579315
TI  - Tolerance in baboon kidney transplantation with total lymphoid irradiation (TLI)
      and anti-CD3/CD4-idarubicin conjugates.
AB  - BACKGROUND: We previously reported the induction of transplantation tolerance by
      a modified wide field method of pretransplant total lymphoid irradiation (TLI),
      cumulative dose 800 cGy, given as 80 or 100 cGy fractions twice/week, in
      approximately one-third of chacma baboons receiving liver or kidney allografts (1
      4) and in vervet monkeys receiving baboon kidney xenografts (5). In this study,
      the effects of the administration of brief courses of anti-CD3 or CD4-Idarubicin
      conjugates on the frequency and predictability of tolerance induction by TLI were
      examined. METHODS: TLI was administered pretransplant in doses of 800, 600, or
      400 cGy. The conjugates were administered either after transplantation in doses
      of 0.25 mg/kg body weight, 3 times/week for 2 weeks, or as a single dose of 1.0
      mg/kg body weight 24 hr before transplantation. RESULTS: Operational tolerance,
      defined as normal graft function >1 year after transplantation, was obtained in
      one-half of six baboons receiving the single dose of 1 mg/kg of Idarubicin
      conjugate pretransplant after 800 cGy of TLI and also in one of four baboons
      treated with 400 cGy of TLI and a single dose of anti-CD3 conjugate before
      transplantation. By contrast, administration of the conjugated antibodies 3
      times/week for 2 weeks after transplantation prevented tolerance induction in all
      animals, providing further evidence for the involvement of active mechanisms,
      capable of inhibition by immunosuppressive agents, in tolerance induction with
      TLI, and of relevance to our reported clinical experience with TLI (6).
      CONCLUSIONS: These promising findings invite further studies with a larger number
      of animals and additional brief regimens of irradiation and antibody dosages and
      specificities.

PMID- 11579316
TI  - Sympathetic reinnervation of rat kidney grafts.
AB  - BACKGROUND: Reinnervation occurs in many transplanted tissues and organs.
      Sympathetic reinnervation in rat kidney grafts was investigated. METHODS: Rats
      were syngeneically transplanted with a kidney and bilaterally nephrectomized.
      Reinnervation was assessed by immunohistochemical staining for neuron-specific
      protein gene product 9.5 (PGP 9.5) and by tissue norepinephrine measurements in
      grafts removed 1.5 (n=6), 3 (n=7), 6 (n=8), and 9 (n=7) months after
      transplantation. RESULTS: PGP 9.5-positive neural structures were significantly
      reduced in grafts removed 1.5 and 3 months after transplantation compared with
      native kidneys with slightly increased numbers at 6 and 9 months after
      transplantation. Median transplant norepinephrine concentrations remained at
      approximately 3% compared with native kidneys until 9 months after
      transplantation. CONCLUSIONS: In transplanted rat kidneys, some reinnervation
      occurs in the hilum within 9 months after transplantation. This is not
      accompanied by a significant recovery of norepinephrine concentration in renal
      tissue indicating persistent sympathetic denervation.

PMID- 11579317
TI  - Adenocarcinoma arising in a transplanted pancreas.
AB  - Tumor transmission or de novo tumor development in the transplanted organ is a
      rare event. Appreciation of the organ-specific risk factors for tumor development
      and careful inspection of the organ at procurement may reduce but not eliminate
      this complication. We report the first known combined kidney-pancreas recipient
      who developed adenocarcinoma in the transplanted pancreas. Molecular typing of
      the tumor by DNA sequencing supports donor derivation of the tumor. Despite
      cessation of immunosuppression and reconstitution of the recipient's immune
      response, the patient died from metastatic pancreatic adenocarcinoma. Comparison
      is made to the reported outcomes after diagnosis of renal cell carcinoma that
      appeared early after transplantation

PMID- 11579318
TI  - Cytotoxic effector molecule gene expression in acute renal allograft rejection:
      correlation with clinical outcome; histopathology and function of the allograft.
AB  - BACKGROUND: Cytotoxic effector molecule expression in human renal allograft
      biopsies has been closely associated with acute rejection. Here we studied
      whether intragraft expression of perforin, granzyme B, and Fas ligand correlates
      with long-term clinical outcome of acute rejection episodes. Furthermore, we
      examined the relation to histopathology and function of the allograft during
      rejection. METHODS: Twenty-two human renal biopsies were quantified for mRNA
      expression of perforin, granzyme B, Fas ligand, and Fas with reverse
      transcription-polymerase chain reaction. Expression levels were correlated with
      clinical outcome after 12 months, Banff rejection grades, and allograft function
      in the course of acute rejection. RESULTS: Only Fas ligand, but not perforin or
      granzyme B, showed significantly higher up-regulation in seven samples with
      therapy-resistant acute rejections versus eight samples with therapy-sensitive
      acute rejection. We found no relation between cytotoxic marker expression and
      Banff rejection grades or serum creatinine peak levels. CONCLUSIONS: Fas ligand
      may be useful as an early marker of therapy-resistant acute rejection. Cells that
      express Fas ligand but not classical soluble cytotoxic molecules might influence
      clinical outcome of acute rejection episodes.

PMID- 11579319
TI  - Impaired exercise performance after successful liver transplantation.
AB  - BACKGROUND: Recipients of heart, lung, and kidney transplants have impaired peak
      exercise performance (peak Vo2 40% to 60% predicted, reduced anaerobic threshold
      [AT]) without evidence of ventilatory or cardiac limitations. The aim of this
      study was to determine whether similar exercise impairment occurs in liver
      transplant recipients. METHODS: We studied eight healthy liver transplant
      recipients (age 42+/-9 [SD] years, 6 male, 31+/-13 months posttransplant).
      Immunosuppression included FK506 or cyclosporine, azathioprine or mycophenolate
      mofetil, and prednisone. Subjects underwent lung function testing and
      cardiopulmonary exercise testing on a cycle ergometer. RESULTS: Peak exercise
      oxygen consumption (Vo2) was 22+/-8 ml/min/kg (66+/-20% predicted maximum). No
      subject demonstrated exercise desaturation or ventilatory limitation (peak minute
      ventilation 55+/-8% predicted maximum voluntary ventilation). Peak heart rate was
      87+/-8% of predicted maximum. Early AT was evident (1.2+/-0.34 L/min, 48+/-11%
      predicted Vo2max). CONCLUSIONS: Liver transplant recipients exhibit impaired peak
      exercise performance similar to that observed after other solid organ
      transplants, possibly as a result of chronic deconditioning or myopathy related
      to immunosuppressive medications.

PMID- 11579320
TI  - The effect of mycophenolate mofetil on hepatitis B viral load in stable renal
      transplant recipients with chronic hepatitis B.

PMID- 11579321
TI  - Interstitial pneumonitis associated with sirolimus (rapamycin) therapy after
      liver transplantation.

PMID- 11579323
TI  - Hope or efficacy in donor liver allocation?
AB  - Both the number of recipients awaiting liver transplantation and the length of
      wait are increasing, giving rise to increasing concern by patients, healthcare
      professionals, and the public. Greater attention has been focused on the criteria
      for listing patients for transplantation and for allocation of organs. In the
      U.K., compared with the U.S., the delivery of liver transplant services is more
      tightly regulated, with fewer transplant centers, lower transplant rates, shorter
      waiting lists, and shorter waiting times. The reasons for these differences are
      unclear. In the U.K., patients are listed only if there is a reasonable
      expectation that the patient will receive a graft. The criteria for listing are
      based on overall utility rather than individual benefit, so the criterion for
      listing is that the patient will have at least a greater than 50% probability of
      being alive 5 years after transplantation with a quality of life that is
      acceptable to the patient. Although it is reasonable to offer hope to all
      patients, this hope should have a reasonable probability of being fulfilled.
      Listing patients with little likelihood of benefiting from transplantation is not
      helpful either for the patient, their family, or the other potential liver
      allograft recipients. While different systems for allocation of donor livers may
      be more appropriate in other settings, the process in the U.K. seems to deliver
      satisfactorily.

PMID- 11579322
TI  - Hope versus efficiency in organ allocation.
AB  - Previous ethical analyses of organ allocation policies have addressed the trade
      off between giving organs to urgent versus non-urgent patients, overlooking the
      process by which patients become urgent in the first place. This article proposes
      three criteria for assessing the performance of organ allocation rules that take
      into account the dynamic nature of patient health. An equitable policy is one
      under which patients' probability of receiving a transplant is equal at listing.
      Efficiency captures the goal of giving organs to patients when their benefit from
      transplantation is greatest. Hope implies that patients should believe that they
      have a reasonable chance of receiving an organ. The sickest first policy, which
      is currently used to prioritize patients, is hope-preserving, but may be
      inefficient. As demand grows relative to supply, patients will only receive an
      organ once they have reached the sickest status category.

PMID- 11579325
TI  - HLA antigens in alkaptonuric patients.
AB  - BACKGROUND: In alkaptonuric patients a disabling ochronotic arthropathy develops,
      due to the deposit of a pigmented polymer of homogentisic acid. Since in
      inherited diseases the clinical expressions may be multifactorial, involving
      genetic and environmental factors, where the HLA system may play a role, we
      studied HLA antigens in ochronotic patients. METHODS: The study was carried out
      in 21 members of three families of six ochronotic patients and in two isolated
      ochronotic patients. The HLA typing has been done testing for antigens from loci
      A, B and C, by international standard microlymphocytotoxicity method, and for
      loci DR and DQ, by fluorescence method on immunologically isolated cells by means
      of antibody-coated microspheres. The chi square test was used for statistical
      analysis, with Yates correction due to the low number of observations. RESULTS:
      Despite the limited number of subjects, due to the rarity of the disease, a
      significantly higher prevalence of HLA-DR7 antigen was found in the alkaptonuric
      patients when compared to a general population (p<0.02), suggesting a possible
      association, while the prevalence of HLA A, B, C and DQ showed no significant
      differences. CONCLUSIONS: It might play a role in the pathophysiology and in the
      clinical expression of the disease.

PMID- 11579326
TI  - Leptin and body composition in healthy postmenopausal women.
AB  - BACKGROUND: Leptin has been proposed to be involved in central control of
      adiposity and fat distribution but the role of this peptide is controversial. The
      aim of our study was to test the relationship between serum leptin and body
      composition, fat distribution, and some biochemical markers such as fasting
      insulinemia and lipoproteins in a population of healthy Italian postmenopausal
      women. METHODS: One hundred and twenty-three postmenopausal women (62.1+/-8.7
      years) were evaluated. Body composition (fat and lean mass) was assessed by dual
      energy X-ray absorptiometry (DXA). Two regions of interest were determined for
      regional fat analysis. Serum leptin and insulinemia were measured by
      radioimmunoassay, lipoproteins with colorimetric methods and apolipoproteins
      nephelometrically. RESULTS: Plasma leptin levels are strongly related to total
      fat mass, in grams (r=0.73, p<0.001) or as a percentage of soft tissue (r=0.75,
      p<0.001), and to adiposity, calculated as ratio between lean and fat mass
      (r=0.76, p<0.001). A significant correlation was also found between serum leptin
      and central fat distribution (r=0.29, p<0.01). As concerns biochemical markers,
      serum leptin was significantly related to fasting insulin (r=0.38, p<0.001),
      total cholesterol (r=0.29, p<0.01), Apolipoprotein-B (r=0.35, p<0.001), and
      triglycerides (r=0.22, p<0.05). When corrected for total fat mass, the partial
      correlation coefficients remain significant for percentage of total body fat
      (r=0.27, p<0.01), adiposity (r=0.23, p<0.01), and fat proportion in android
      region (r=0.18, p<0.05). CONCLUSIONS: These data indicate that leptin levels are
      related to adiposity and fasting insulin levels; indeed fast insulin mantains
      significant correlation with leptin (r=0.23, p<0.01) after controlling for fat
      mass. Android distribution of fat mass in elderly women is associated with leptin
      concentration.

PMID- 11579327
TI  - Infants of immigrant parents in Italy. A national multicentre case control study.
AB  - BACKGROUND: The aim of this study was to evaluate health state of newborns of
      immigrated parents from developing countries. METHODS: Hospital records of 69,605
      infants born during 1996/1997 in Italy were reviewed comparing, in a case-control
      study, each infant of immigrated parents to two infants born immediately before
      and after to Italian parents. RESULTS: Of the 69,605 newborns 3906 (5.6%) were
      born to immigrated parents. This prevalence prolongs the increasing trend
      observed during the last 10 years of infants born to immigrated parents and
      reduces the fall of the birth rate linked to the few infants born to Italian
      parents. It was influenced by geographical factors, being higher in Northern
      Central Italy (7%) than in Southern and Insular Italy (2.8%), as consequence of
      more elevated incomes in these Italian regions. The origin countries of
      immigrated parents were mainly Northern Africa (31.7%), Eastern Europe (18%) and
      Sub Saharan Africa (11.6%). Infants of immigrated parents showed higher
      incidences of prematurity, low birth weight, asphyxia and neonatal mortality rate
      than newborns with Italian parents. These higher incidences appeared related to
      some risk factors such as higher parity, short gestational age, some maternal
      infections, maternal drug dependence, maternal age less than 18 years, low
      familiar income, inadequate obstetric cares, difficulty to accessing the public
      health services. CONCLUSIONS: The health problems of infants with immigrated
      parents are mainly related to social disadvantage and can be overcome improving
      the social state, the lifestyles and the obstetric cares of the immigrated women,
      so as monitoring their risk pregnancies.

PMID- 11579328
TI  - Therapeutic approach in pulmonary mycetoma. Analysis of 27 patients.
AB  - BACKGROUND: Pulmonary mycetoma is a characteristic clinical-radiological lesion
      due to colonization of aspergillus or candida species in pre-existing pulmonary
      cavities following a number of diseases. METHODS: We revisited 27 records of such
      admitted patients (19 M, 8 F; range age 16-27 yrs) analysing diagnostic approach
      and therapy. Predisposing conditions were sequelae of tuberculosis or lung
      abscess, bronchiectasis, bullous emphysema, leukaemia/ lymphoma, diabetes
      mellitus, corticosteroids and/or immunosuppressant administration and antiblastic
      chemotherapy. All patients had a characteristic chest X-ray and the most common
      symptoms were cough and haemoptysis. Diagnosis of pulmonary mycetoma was based on
      positive sputum culture for aspergillus or candida species and/or positive result
      for aspergillus precipitin test. Eleven patients received only medical treatment,
      eight pts only a surgical one and eight patients both medical and surgical ones.
      Antifungal drugs administered were itraconazole or amphotericin B or fluconazole.
      RESULTS: In the follow-up, six out of eleven patients who had received only
      medical treatment, cannot be found; five patients or their relatives were
      interviewed by phone: two of them enjoyed good health and three had died. Sixteen
      patients underwent thoracic surgery and one of them died because of postsurgical
      complications. In the follow-up, only nine patients out of this last group were
      interviewed by phone 2 to 8 years after surgery: seven of them enjoyed good
      health while two patients had died because of disease not related to pulmonary
      mycetoma. CONCLUSIONS: Aspergilloma treatment is related to the extension of
      disease and clinical conditions of patients but surgical resection associated
      with drug administration, when possible, is the treatment of choice.

PMID- 11579329
TI  - Lymph node dissection in surgical treatment of esophageal neoplasms.
AB  - BACKGROUND: Until now therapy of carcinoma of the esophagus has presented an aura
      of pessimism, resulting in an attitude among physicians that cure was impossible.
      Presently the overall 5-year survival is between 38.3% and 55% thanks to new
      radical surgical techniques. The aim of this work is to evaluate lymph node
      dissection in treatment of esophageal carcinoma by analyzing morbidity,
      mortality, survival and quality of life. METHODS: From 1975 to 1995, 170 patients
      with carcinoma of the esophagus and cardia underwent operation, of whom 165
      underwent 2-field lymphadenectomy and four 3-field lymphadenectomy; one patient
      was submitted to self-transplanting jejunal loop to neck. One hundred and twenty
      two patients had standard resection and 47 en bloc resection. RESULTS: Lymph node
      involvement is often found in patients with superficial carcinoma and it greatly
      influences outcome after esophagectomy. In 2-field lymphadenectomy morbidity and
      mortality are more frequent in en bloc resections; global 3-year survival was
      better in patients with early lesions. Three-field lymphadenectomy was performed
      in only few cases, not sufficient to express a definitive opinion. CONCLUSIONS:
      On the basis of our experience, we conclude that the better survival is
      particularly dependent on early diagnosis, histological type of neoplasia and
      following surgical treatment, especially on the type of resection with 2 or 3
      field lymphadenectomy.

PMID- 11579330
TI  - The effect of preemptive intravenous morphine on postoperative analgesia and
      surgical stress response.
AB  - BACKGROUND: Although initial studies of preemptive analgesia showed that
      preoperative blockade with local anaesthetics or preoperative administration of
      systemic opioids was more effective in reducing postoperative pain than control
      conditions involving no treatment, the result of subsequent investigations
      comparing the effects of preoperative treatment with the same treatment initiated
      after surgery have produced inconsistent RESULTS. The reasons for the lack of
      consistency are not clear. Studies about the relationship of preemptive analgesia
      and both analgesic consumption and surgical stress response are limited. The
      purpose of this study was to evaluate the effect of preemptive intravenous
      morphine on both postoperative analgesic consumption and surgical stress
      response. METHODS: Sixty patients, ASA I or II, aged 20-60, undergoing total
      abdominal hysterectomy plus bilateral salpingo-oopherectomy and double-blinded
      were randomly assigned to three groups of 20 patients. Group I (n=20) received
      0.15 mg/kg of morphine following induction and placebo saline during peritoneal
      closure. Group II (n=20) received placebo saline following induction and 0.15
      mg/kg of morphine during peritoneal closure. Group III (n=20) received placebo
      saline both during induction and peritoneal closure. Blood cortisol, glucose
      levels and leukocyte count were measured in the pre and postoperative period.
      RESULTS: Postoperative total morphine consumption was significantly lower in
      group I compared with group III (p<0.001). In all groups, plasma cortisol levels
      increased significantly within 4 hours of surgery as compared to pre-op values
      (p<0.001). Plasma glucose also increased to a significantly higher level in all
      groups in the postoperative 30 min and 8 hours than in the pre-op values
      (p<0.001). Postoperative leukocytosis was observed in all groups and the
      leukocyte count was significantly greater during postoperative 24 h than pre-op
      values (p<0.001). CONCLUSIONS: Preemptive morphine 0.15 mg/kg intravenous has
      decreased total morphine consumption but has failed to suppress the surgical
      stress response.

PMID- 11579331
TI  - Hypomagnesemia. A review of pathophysiological, clinical and therapeutical
      aspects.
AB  - The aim of this paper is to discuss, on the basis of an extensive literature
      review, the role of magnesium (Mg) in health and disease. Mg is an essential
      cation playing a crucial role in many enzyme systems. Quantitative Mg body stores
      are regulated by metabolic and hormonal effects on gastrointestinal absorption
      and renal excretion. Mg is a smooth muscle relaxant, dilates coronary arteries
      and peripheral vessels, exerts antiarrhythmic effects, may have a permissive
      effect on catecholamine actions and can play a role in various thrombogenic
      conditions. Today, hypomagnesemia has become a recognized medical occurrence
      which may be associated with many different diseases, either genetic or acquired.
      Mg deficiency is one of the most frequent electrolyte abnormalities in clinical
      practice, but it is probably the most underdiagnosed one. Clinical manifestations
      of hypomagnesemia may begin insidiously or dramatically sudden. A large part of
      the population (especially aged subjects) may have an inadequate Mg intake and a
      chronic latent Mg deficiency. Routine inclusion of serum Mg analysis in the
      electrolyte panel represents a continued need to recognize hypomagnesemia and to
      treat Mg-depleted patients. New clinical studies on Mg deficiency are necessary
      to ascertain the usefulness and cost-effectiveness of Mg replacement therapy.

PMID- 11579332
TI  - Kearns-Sayre syndrome associated with de Toni-Debre-Fanconi syndrome due to
      cytochrome-c-oxidase (COX) deficiency.
AB  - We report a 43-year-old female with complete Kearns-Sayre syndrome, focal
      deficiency of cytochrome-c-oxidase (COX) and extensive deletion of the mtDNA in
      muscle fibers, which showed progressive insufficiency of the renal tubule: first
      hyperphosphaturia and hyperaminoaciduria and, later, also glucosuria (de Toni
      Debre-Fanconi syndrome), a syndrome to date rarely diagnosed in association with
      complete Kearns-Sayre syndrome. In our opinion, this case, in view of the
      relationships between retinal and kidney disorders, suggests a search for de Toni
      Debre-Fanconi syndrome in all patients with Kearns-Sayre syndrome also by
      quantitative and chromatographic methods for the assessment of aminoacids,
      phosphates and sugars in the urine.

PMID- 11579333
TI  - Antioxidant activity of carbocysteine lysine salt monohydrate.
AB  - BACKGROUND: Reactive oxygen radicals are involved in many respiratory diseases,
      including chronic obstructive pulmonary disease (COPD). Carbocysteine lysine salt
      monohydrate (CLS) is a mucoactive drug effective in the treatment of
      bronchopulmonary diseases characterized by mucus alterations, including COPD. In
      the present study, the antioxidant activity of CLS was studied in vitro in three
      different oxygen radical producing systems, i.e. bronchoalveolar lavages (BAL)
      from patients affected by COPD, ultrasound treated human serum and cultured human
      lung endothelial cells challenged with elastase. METHODS: BAL, exposed or not to
      different concentrations of CLS (1.5-30 mM), was assayed for free radical content
      by fluorometric analysis of DNA unwinding (FADU) or by cytochrome c reduction
      kinetics. Human serum was treated with ultrasound in the presence or absence of
      CLS (1.5, 2.5 mM) or N-acetyl cysteine (NAC; 4, 5 mM) and assayed for free
      radical content by FADU. Human endothelial cells cultured in vitro from pulmonary
      artery were incubated with elastase (0.3 IU/mL), in the presence or absence of
      glutathione (GSH; 0.65 mM) or CLS (0.16 mM). The supernatant was tested for
      cytochrome c reduction kinetics whereas cell homogenates were assessed for
      xanthine oxidase (XO) content by SDS-PAGE. RESULTS: Results showed that CLS is
      more effective as an in vitro scavenger in comparison to GSH and NAC. CLS reduced
      the damage of DNA from healthy donors exposed to COPD-BAL and was able to quench
      clastogenic activity induced in human serum by exposure to ultrasound at
      concentrations as low as 2.5 mM. NAC protect DNA from radical damage, starting
      from 5 mM. In human lung endothelial cells cultured in presence of elastase, CLS
      (0.16 mM) decreased xanthine oxidase activity. CONCLUSIONS: These results suggest
      that CLS could act by interfering with the conversion of xanthine dehydrogenase
      into superoxide-producing xanthine oxidase. The antioxidant activity of CLS could
      contribute to its therapeutic activity by reducing radical damage to different
      lung structures.

PMID- 11579335
TI  - Magnetic resonance imaging of the breast.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has the potential to become a useful
      adjunct in breast imaging. Contrast-enhanced breast MRI has demonstrated a high
      sensitivity in the detection of invasive breast cancer. In clinical studies,
      breast MRI has often altered the course of patient care. Although promising
      results have been generated, MRI of the breast is currently in a development
      stage. METHODS: The authors reviewed the literature on the potential indications,
      sensitivity, specificity, and limitations of MRI of the breast. RESULTS: Reported
      advantages of MRI of the breast over conventional imaging techniques include
      improved staging and treatment planning, enhanced evaluation of the augmented
      breast, better detection of recurrence, and improved screening of high-risk
      women. Contrast-enhanced breast MRI is a sensitive modality for detecting breast
      cancer, but its variable specificity is a major limitation. CONCLUSIONS: MRI of
      the breast is emerging as a valuable adjunct to mammography and sonography for
      specific clinical indications. Additional clinical studies that define
      indications, interpretation criteria, imaging parameters, and cost effectiveness
      are needed. A multi-institutional study designed to address these issues is in
      progress.

PMID- 11579336
TI  - Breast cancer sentinel node metastases: histopathologic detection and clinical
      significance.
AB  - BACKGROUND: Lymphatic mapping with sentinel lymphadenectomy (LM/SL) is an
      accurate and less morbid means of determining the tumor status of the axilla in
      breast cancer patients than standard level I and II axillary lymph node
      dissection (ALND). This review addresses the handling and pathologic examination
      of the sentinel node (SN), the clinical significance of tumor within the SN, and
      the risk factors for non-SN tumor involvement. METHODS: The seminal works that
      have addressed pathologic examination of ALND specimens and SN specimens are
      summarized, and the important studies attempting to identify predictors of non-SN
      metastases in patients with a tumor-involved SN are reviewed. RESULTS: Standard
      single-section hematoxylin-eosin (H&E) examination is inadequate for reliable
      detection of axillary or SN metastases. Large studies appropriately powered to
      detect a survival difference for patients with micrometastatic disease are
      reviewed. The current data on the clinical significance of micrometastatic nodal
      disease is inconclusive. While several strong predictors of non-SN tumor
      involvement have been identified, none is reliable enough to allow omission of
      ALND in patients with a tumor-involved SN. CONCLUSIONS: Routine examination of
      the SN specimen should include serial sections with H&E stain. Ongoing
      prospective clinical trials should help to define the clinical significance of SN
      micrometastases. Furthermore, these trials could help identify predictors of non
      SN metastasis that would allow a subset of patients with a tumor-involved SN to
      avoid the morbidity of ALND.

PMID- 11579337
TI  - Laboratory testing for HER2/neu in breast carcinoma: an evolving strategy to
      predict response to targeted therapy.
AB  - BACKGROUND: Laboratory testing of HER2/neu in breast carcinoma has become vital
      to patient care following the approval of trastuzumab as the first therapy to
      target the HER2/neu oncoprotein. Initial clinical trials used
      immunohistochemistry (IHC) to test for HER2/neu overexpression in order to select
      patients for therapy. Fluorescence in situ hybridization (FISH), which tests for
      gene amplification, is more specific and sensitive than IHC when either assay is
      compared with HER2/neu overexpression as determined by Northern or Western blot
      analysis. Many weak overexpressors on IHC testing are not gene amplified on FISH
      analysis. Such weak overexpressors may be considered false-positives and raise
      the question of how best to test for HER2/neu. METHODS: The literature was
      surveyed regarding testing for HER2/neu overexpression in breast carcinomas and
      alternative testing strategies. RESULTS: False-positive results are a significant
      problem when IHC is exclusively used to test for HER2/neu overexpression. The
      false-positives are overwhelmingly confined to the group of 2+ positives and do
      not respond to targeted therapy. In contrast, concordance between IHC and FISH is
      high when immunostaining is interpreted as either negative or strongly positive
      (3+). Whereas some recent studies have suggested that FISH may better predict
      response to anti-HER2/neu therapy than IHC, others have indicated that IHC is as
      effective a predictor as FISH. IHC is less technically demanding and costly than
      FISH. CONCLUSIONS: IHC analysis of HER2/neu in breast carcinoma is a useful
      predictor of response to therapy with trastuzumab when strongly positive.
      Negative immunostaining is highly concordant with a lack of gene amplification by
      FISH. Most weakly positive overexpressors are false-positives on testing with
      FISH. Thus, screening of breast carcinomas with IHC and confirmation of weakly
      positive IHC results by FISH is an effective evolving strategy for testing
      HER2/neu as a predictor of response to targeted therapy.

PMID- 11579338
TI  - Postmastectomy breast reconstruction: current techniques.
AB  - BACKGROUND: The techniques of breast reconstruction have evolved and matured over
      the past 25 years. Recent studies have proven the benefit of breast
      reconstruction for breast cancer patients. METHODS: The authors reviewed the
      recent literature on the techniques of breast reconstruction and the effects of
      reconstruction on patients following surgery for breast cancer. The findings in
      recent studies are correlated with the experience of the authors. RESULTS: A
      better understanding has been gained regarding surgical techniques of breast
      reconstruction as well as the proper indications for the various methods. The
      criteria of patient benefit have been defined by recent long-term studies.
      CONCLUSIONS: Breast reconstruction following mastectomy has been proven to be a
      safe and beneficial procedure.

PMID- 11579339
TI  - The effect of sentinel node selective axillary lymphadenectomy on the incidence
      of postmastectomy pain syndrome.
AB  - BACKGROUND: Postmastectomy pain syndrome (PMPS) has been reported following
      procedures involving complete lymph node dissection (CLND). Since the triggering
      event is probably related to nerve injury, sentinel lymph node dissection (SLND)
      should decrease the incidence of PMPS. The purpose of this report is to determine
      the impact of SLND on the number of patients referred to the pain clinic for PMPS
      treatment. METHODS: The records of all breast surgical patients with a diagnosis
      of PMPS referred to the Moffitt Cancer Center pain clinic were reviewed. The
      criterion for diagnosis of PMPS was a history of postoperative pain in the upper
      anterior chest wall, upper extremity, axilla, and/or shoulder in the absence of
      recurrent disease. RESULTS: A total of 55 patients with a diagnosis of PMPS were
      seen in the pain clinic since 1991. Treatments included local
      anesthetics/corticosteroid injection, stellate ganglion block, and tricyclic
      antidepressants. A decrease from 15 patients in 1991 to 3 in 1998 was observed.
      All but one of the 55 patients with PMPS had CLND, and none referred to the pain
      clinic had undergone SLND. CONCLUSIONS: PMPS is a complication of CLND. The
      increased use of SLND in our center has reduced the number of referrals to the
      pain clinic for treatment of PMPS. This benefit of SLND reduces suffering in the
      postoperative breast patient.

PMID- 11579340
TI  - Management of breast cancer in the older woman.
AB  - BACKGROUND: Approximately half of all breast cancer cases occur after age 65.
      Several aspects for the treatment of early breast cancer may be influenced by
      patient age, including postoperative irradiation after partial mastectomy,
      axillary lymphadenectomy, primary medical treatment of early breast cancer, and
      adjuvant chemotherapy. METHODS: The authors review the literature regarding age
      specific issues in the management of breast cancer, and they report their own
      experience in treating older women with breast cancer. RESULTS: In terms of
      survival and disease-free survival, tamoxifen alone in primary breast cancer is
      inferior to surgical treatment followed by adjuvant tamoxifen. Tamoxifen alone
      should be reserved for patients with absolute contraindications to mastectomy.
      Adjuvant chemotherapy is beneficial to women with hormone receptor-poor tumors.
      In those with hormone receptor-rich tumors, adjuvant chemotherapy is beneficial
      for HER2-positive tumors, and the regimen should contain an anthracycline.
      CONCLUSIONS: Although the risk of local recurrence after partial mastectomy
      declines with increasing age, the decision to forego radiation therapy is
      individualized based on risk of recurrence and on patient desires and resources.
      The advent of lymph node mapping obviates the need for lymphadenectomy in most
      patients. The benefits and risks of adjuvant chemotherapy should be individually
      assessed according to tumor stage, life expectancy, comorbidity, and expected
      tolerance of treatment.

PMID- 11579341
TI  - Sexual functioning in breast cancer survivors.
AB  - BACKGROUND: A growing body of evidence suggests that sexual dysfunction may be
      among the more common and distressing symptoms experienced by breast cancer
      survivors. METHODS: This report reviews studies in which sexual functioning in
      breast cancer survivors has been investigated. Included are reports on the
      prevalence and nature of sexual difficulties, the relationship between specific
      breast cancer treatments and sexual difficulties, and the treatment of sexual
      dysfunction following completion of breast cancer treatment. RESULTS: A review of
      the literature suggests a wide range of rates for the prevalence of sexual
      problems in breast cancer survivors. Factors that may affect prevalence rates
      include the methods used to determine prevalence and the demographic and medical
      characteristics of the patients studied. With regard to treatment effects,
      evidence suggests that breast cancer patients who undergo chemotherapy are at
      high risk for sexual dysfunction after treatment. In contrast, there is little
      evidence of a link between type of surgical treatment (eg, lumpectomy vs
      mastectomy) or treatment with tamoxifen and sexual functioning outcomes.
      CONCLUSIONS: A growing body of evidence suggests that sexual problems can be a
      long-term side effect of breast cancer treatment. Oncology professionals should
      initiate communication about sexual difficulties, perform comprehensive
      assessments, and educate and counsel patients about the management of these
      difficulties.

PMID- 11579342
TI  - Carcinoid heart disease: medical and surgical considerations.

PMID- 11579343
TI  - Combination of minimally invasive coronary bypass and percutaneous transluminal
      coronary angioplasty in the treatment of double-vessel coronary disease: Two-year
      follow-up of a new hybrid procedure compared with "on-pump" double bypass
      grafting.
AB  - OBJECTIVE: Percutaneous transluminal coronary angioplasty (PTCA) or surgery can
      be chosen as first-line therapies in multiple-vessel coronary disease. A mammary
      to-left anterior descending (LAD) graft is the most important statistical
      determinant of a favorable outcome after coronary artery bypass grafting (CABG)
      and can be performed with lower morbidity off pump through a minithoracotomy.
      PTCA and stenting of the "non-LAD" vessels compete with CABG in terms of patency
      rates. Our purpose was to compare a combination of minimally invasive direct
      coronary artery bypass (MIDCAB) and PTCA with double CABG as a treatment for
      double-vessel coronary artery disease involving the proximal LAD. METHODS: Two
      matched groups of 20 patients with double-vessel coronary disease undergoing
      either sequential MIDCAB and PTCA (group 1) or double CABG on cardiopulmonary
      bypass (group 2) were compared. Angiographic control, complications, hospital
      costs, quality of life, and 2-year follow-up of ischemia are reported. RESULTS:
      All bypasses were patent at early control. Three adverse events were noted in
      group 1 and 17 in group 2. The hybrid-procedure group exhibited a shorter
      intensive care unit stay, fewer blood products transfused, less pain, better
      early quality of life, faster return to work, and similar cost. Three patients
      required a second PTCA in group 1, one of which for restenosis. At 2 years all
      the patients are asymptomatic with no residual ischemia. CONCLUSIONS: We conclude
      from this pilot study that the hybrid procedure is feasible and appears to be a
      safe therapy for double-vessel coronary artery disease and that it appears to
      generate less perioperative morbidity than classic double CABG does. Therefore we
      believe that there is room to undertake prospective randomized studies on a
      larger-scale basis.

PMID- 11579344
TI  - Seven cases of surgical native valve endocarditis caused by coagulase-negative
      staphylococci: An underappreciated disease.
AB  - BACKGROUND: Native valve endocarditis caused by coagulase-negative staphylococci
      is uncommon and the diagnosis is infrequently considered. The disease, however,
      appears to be increasing in frequency and can pursue an aggressive clinical
      course. We report the clinical features of 7 cases of coagulase-negative
      staphylococcal native valve endocarditis (CNS-NVE) seen at 1 institution with a
      large cardiovascular referral base over a 10-month period. All cases required
      valve replacement surgery. METHODS: Clinical history, echocardiograms, and
      microbiologic and histopathologic data were reviewed for 7 patients with surgical
      CNS-NVE. RESULTS: Four patients had intravenous central catheters, and 1 had
      recent surgery, whereas the remaining 2 had no identifiable risk factors.
      Presentations ranged from subacute (4 cases) to acute with complications (3
      cases). Complications included congestive heart failure, stroke, and heart block.
      Echocardiography demonstrated valvular lesions in all 7 cases. Valve pathologic
      study demonstrated gram-positive cocci in all 7 cases; blood cultures grew
      coagulase-negative staphylococci in 6 cases and valve cultures grew
      Staphylococcus epidermidis in 5 cases. CONCLUSIONS: Coagulase-negative
      staphylococci, including S epidermidis, can cause severe native valve
      endocarditis requiring valve replacement. The increasing use of intravascular
      access devices in the community may herald an increase in the incidence of CNS
      NVE. A high index of diagnostic suspicion in the appropriate clinical setting is
      critical for optimal management.

PMID- 11579345
TI  - Design and baseline characteristics for the ACE Inhibitor After Anthracycline
      (AAA) study of cardiac dysfunction in long-term pediatric cancer survivors.
AB  - PURPOSE: The ACE Inhibitor After Anthracycline (AAA) study is a randomized,
      double-blind, controlled clinical trial comparing enalapril with placebo to
      determine whether treatment can slow the progression of cardiac decline in
      patients who screen positive for anthracycline cardiotoxicity. METHODS: The
      primary outcome measure is the rate of decline, over time, in maximal cardiac
      index (in liters per minute per meters squared) at peak exercise; the secondary
      outcome measure is the rate of increase in left ventricular end systolic wall
      stress (in grams per centimeters squared). Patients >2 years off therapy and <4
      years from diagnosis, aged 8 years and older, were eligible if they had received
      anthracyclines and had at least one cardiac abnormality identified at any time
      after anthracycline exposure. RESULTS: A total of 135 patients were randomized to
      enalapril or placebo. Baseline characteristics were similar across treatment
      groups. CONCLUSIONS: The AAA study will provide important information concerning
      the efficacy of using angiotensin-converting enzyme inhibitors to offset the
      effects of late anthracycline cardiotoxicity.

PMID- 11579346
TI  - Relationship of the Glu298Asp polymorphism of the endothelial nitric oxide
      synthase gene and early-onset coronary artery disease.
AB  - BACKGROUND: The Glu298Asp polymorphism of endothelial nitric oxide synthase
      (eNOS) gene has been associated with coronary artery disease (CAD) in some but
      not all studies. To determine the impact of the mutant Asp298 eNOS allele on the
      development of premature CAD, we examined the prevalence of this mutation in
      patients with early-onset CAD compared with those manifesting CAD later in life.
      If this mutation confers an increased risk of premature CAD, we hypothesized that
      the frequency of the homozygous mutation (Asp298Asp298) would be greater among
      the younger patient group. METHODS: A total of 299 patients with a history of
      myocardial infarction (MI) or angina pectoris plus angiographically documented
      CAD were studied. Patients were divided into 2 groups: group 1 (149 patients)
      included patients with CAD before the age of 50 years and group 2 (150 patients)
      included patients with a first presentation of CAD at >65 years old. Prevalence
      of eNOS Glu298 and Asp298 alleles was assessed by molecular analysis and compared
      for the 2 groups. RESULTS: There was no significant difference in the frequency
      of the mutant Asp298 allele between the 2 groups (G1: 42% vs G2: 42.7%, P =.79).
      The frequencies of the Glu298Glu298, Glu298Asp298, and Asp298Asp298 genotypes
      were similar in both groups (34.9%, 46.3%, and 18.8% for G1 and 29.3%, 56%, and
      14.7% for G2, respectively, P =.29). CONCLUSIONS: Our study does not support the
      conclusion that the eNOS Asp298 allele contributes to the development of
      premature CAD.

PMID- 11579347
TI  - Are activated clotting times helpful in the management of anticoagulation with
      subcutaneous low-molecular-weight heparin?
AB  - BACKGROUND: Enoxaparin has recently been shown to be superior to unfractionated
      heparin in patients with unstable angina/non-ST-elevation myocardial infarction.
      Theoretical advantages of low-molecular-weight heparin versus unfractionated
      heparin include a higher ratio of anti-Xa to anti-IIa activity (3:1 for
      enoxaparin), a more predictable dose response that precludes the need for
      frequent monitoring, and the convenience of subcutaneous administration. Both
      activated partial thromboplastin time and activated clotting time (ACT) are used
      to monitor anticoagulation with heparin, and ACTs are now standard during
      percutaneous coronary intervention (PCI) with heparin. At doses of up to 90 mg,
      subcutaneous enoxaparin leads to a modest dose-related increase in activated
      partial thromboplastin time, but the effect on ACT is unknown. METHODS:
      Thrombolysis In Myocardial Infarction (TIMI) 11A was a multicenter, dose-ranging
      trial to evaluate the safety and tolerability of subcutaneous enoxaparin in
      patients with unstable angina/non-ST-elevation myocardial infarction. We obtained
      peak (mean 4.3 hours after enoxaparin) and trough (mean 11.5 hours after
      enoxaparin) anti-Xa levels and ACTs for 26 patients in the TIMI 11A trial.
      RESULTS: Despite doses of enoxaparin in the range of 89 +/- 19 mg every 12 hours
      and significant increases in anti-Xa levels even at trough, there was no change
      in the ACT measured by HemoTec and only a small increase with Hemachron. The
      correlation of peak Hemachron ACT with peak anti-Xa levels was poor (R = 0.5, P
      =.08). CONCLUSIONS: In contrast to heparin, ACTs are not useful for assessment of
      anticoagulation with subcutaneous enoxaparin and should not be relied on in
      patients receiving enoxaparin who require acute PCI. Studies to determine the
      optimal dose, safety, and efficacy of enoxaparin in patients undergoing PCI are
      underway.

PMID- 11579348
TI  - Decade-long trends (1986 to 1997) in the medical treatment of patients with acute
      myocardial infarction: A community-wide perspective.
AB  - BACKGROUND: Although there are an increasing number and variety of medications
      available for the treatment of patients with acute myocardial infarction (AMI),
      few data are available describing recent, and changes over time in, use of
      different cardiac medications in patients with AMI from a more generalizable,
      community-wide perspective. Moreover, it is unclear whether the demographic and
      clinical profile of patients receiving these agents is similar or varies
      according to the type of agent prescribed. METHODS AND RESULTS: The purpose of
      this study was to examine recent patterns and changes over a decade-long period
      (1986 to 1997) in the use of cardiac medications during the acute hospitalization
      and at the time of hospital discharge in metropolitan Worcester, Mass, residents
      (1990 census estimate, 437,000) hospitalized with confirmed AMI. There was a
      marked increase in the use of angiotensin-converting enzyme inhibitors, aspirin,
      beta-blockers, lipid-lowering agents, and thrombolytic therapy between 1986 and
      1997. The use of calcium antagonists, lidocaine, and other antiarrhythmic agents
      declined over this period. Similar trends were observed in the use of these
      agents in hospital survivors at the time of hospital discharge. Patient age,
      presence of comorbidities, and AMI-associated characteristics influenced the use
      of these therapies; sex differences in the use of several of these medications
      were also noted. CONCLUSIONS: The results of this population-based observational
      study provide insights into changing prescribing patterns in the hospital
      treatment of patients with AMI. Despite encouraging increases in the use of
      several of these agents, considerable opportunities for increased utilization
      remain.

PMID- 11579349
TI  - Underutilization of reperfusion therapy in eligible African Americans with acute
      myocardial infarction: Role of presentation and evaluation characteristics.
AB  - BACKGROUND: Immediate reperfusion therapy to restore coronary blood flow is
      recommended for all eligible patients with acute myocardial infarction. However,
      reperfusion therapy is reportedly underutilized among African Americans, even
      when they are eligible. Reasons for the lack of use have not been fully explored.
      METHODS: We examined the demographic, clinical, and treatment data of 10,469
      African Americans with acute myocardial infarction who were eligible for
      reperfusion therapy, enrolled in the National Registry of Myocardial Infarction-2
      from June 1994 through March 1998. RESULTS: The mean age was 62.58 (+/-14.4)
      years, and 44.7% were female. Although eligible, 47% of the African Americans in
      this study did not receive reperfusion therapy. In a multivariate analysis, the
      absence of chest pain at presentation (odds ratio [OR] 0.31, 95% CI 0.26-0.37)
      and initial admission diagnoses other than definite myocardial infarction (OR for
      receipt of reperfusion <0.12) were the strongest predictors of lack of early
      reperfusion therapy. Progressive delays in hospital arrival and hospital
      evaluation predicted a lower likelihood of early reperfusion. Prior stroke (OR
      0.63, 95% CI 0.50-0.78), myocardial infarction (OR 0.75, 95% CI 0.65-0.86), and
      congestive heart failure (OR 0.49, 95% CI 0.40-0.60) were all associated with
      lack of reperfusion therapy. CONCLUSION: Almost half of eligible African American
      patients with myocardial infarction did not receive reperfusion therapy.
      Potential reasons may include atypical presentation, patient and institutional
      delay, and underappreciation of myocardial infarction by care providers.
      Strategies to address these factors may improve the rate of use of reperfusion
      therapy.

PMID- 11579350
TI  - Uniform platelet activation exists before coronary stent implantation despite
      aspirin therapy.
AB  - BACKGROUND: Platelets play an important role in the natural history of coronary
      artery disease. Enhanced platelet aggregation and receptor expression
      unquestionably occur after coronary stent implantation; however, the functional
      characteristics of platelets before stenting have not been fully elucidated.
      METHODS: Platelets were assessed before intervention by platelet-rich plasma
      aggregation (PA) with 5 mmol adenosine diphosphate (ADP) and 1 mg/mL collagen;
      whole blood aggregation (WBA) by 1 mg/mL collagen; shear-induced closure time
      (CT); contractile force (CF); and expression of 9 surface receptors by flow
      cytometry in 126 patients undergoing elective coronary artery stent placement.
      All patients received aspirin for at least 7 days. The data were compared with
      those from 64 healthy volunteers. RESULTS: Each test revealed sustained platelet
      activation in patients undergoing coronary stenting compared with control values.
      These differences were significant for collagen-induced PA (P =.031); CF (P
      =.0001); expression of glycoprotein (GP) IIb/IIIa (P =.0001); P-selectin (P
      =.0008); platelet/endothelial cell adhesion molecule (PECAM)-1 (P =.0001); CD107a
      (P =.0001); CD107b (P =.0004); and CD63 (P =.009). CONCLUSION: Platelets are
      indeed activated before coronary stenting despite antecedent therapy with
      aspirin.

PMID- 11579351
TI  - Effect of sertraline on the recovery rate of cardiac autonomic function in
      depressed patients after acute myocardial infarction.
AB  - BACKGROUND: Brain serotonin is known to possess sympathoinhibitory properties.
      The aim of this clinical physiologic study was to determine whether sertraline, a
      selective serotonin reuptake inhibitor, facilitates the rate of recovery of
      cardiac autonomic function after an acute myocardial infarction (MI) in patients
      with depression. METHODS AND RESULTS: Thirty-eight post-MI depressed patients
      were randomized to receive either sertraline 50 mg per day or placebo for 6
      months. Depression was defined as a score >15 on the standardized Inventory to
      Diagnose Depression questionnaire taken at prehospital discharge and again within
      2 weeks of the acute infarct. Eleven stable post-MI nondepressed patients served
      as a nonrandomized reference group during follow-up. Twenty-seven patients
      completed the randomization. All 3 groups were followed up closely in a
      multidisciplinary post-MI clinic where they underwent serial testing for both
      time and frequency domain heart rate variability (HRV) indices at baseline (1-2
      weeks after MI) and at 6, 10, 14, 18, and 22 weeks. The rate of recovery of HRV
      was determined by use of a growth curve model based on repeated-measures analysis
      of variance. There was a linear rate of increase in the SD of 24-hour N-N
      intervals (SDNN) in the sertraline-treated group that paralleled that of the
      nondepressed reference group. This contrasted with a modest but significant
      decline in SDNN in the placebo group from 2 to 22 weeks (t = 2.10, P <.05).
      However, the short-term power spectral indices, while trending toward a more
      rapid rate of recovery in the treated group, did not reach statistical
      significance compared with the placebo group. CONCLUSION: In depressed patients
      who have survived the acute phase of an MI sertraline facilitates the rate of
      recovery of SDNN, a recognized predictor of clinical outcome.

PMID- 11579352
TI  - Important factors for the 10-year mortality rate in patients with acute chest
      pain or other symptoms consistent with acute myocardial infarction with
      particular emphasis on the influence of age.
AB  - OBJECTIVE: Our purpose was to describe the mortality rate and mode of death over
      10 years and factors associated with death among patients admitted to the
      emergency department with acute chest pain or other symptoms consistent with
      acute myocardial infarction (AMI). METHODS: All patients who came to the
      emergency department at Sahlgrenska University Hospital in Goteborg, Sweden, with
      acute chest pain or other symptoms consistent with AMI during a 21-month period
      were studied. RESULTS: In all, 5362 patients were registered, for whom
      information on 10-year mortality was available in 5158 (96.2%). In all, there
      were 2126 deaths (41.2%). Fifty-two percent of patients were </=65 years old.
      Independent predictors of death registered on admission to hospital during the
      subsequent 10 years were age (relative risk 1.08, 95% CI 1.07-1.09), male sex
      (1.38, 1.25-1.52), initial degree of suspicion of AMI (1.13, 1.06-1.19), a
      pathologic initial electrocardiogram (1.76, 1.56-1.98), symptoms of congestive
      heart failure (1.66, 1.39-1.98), "other" nonspecific symptoms (1.22, 1.07-1.39),
      a history of diabetes mellitus (1.65, 1.44-1.88), a history of congestive heart
      failure (1.42, 1.26-1.60), a history of previous myocardial infarction (1.26,
      1.12-1.40), and a history of hypertension (1.14, 1.03-1.26). For all these
      predictors there was a strong interaction with age, thus a much more marked
      influence on outcome among patients </=65 years old than among patients >65 years
      old. When the above risk indicators were simultaneously considered, development
      of AMI during the first 3 days after hospital admission was still an independent
      predictor of death (1.63, 1.43-1.86). CONCLUSION: For patients admitted to the
      emergency department with acute chest pain or other symptoms consistent with AMI,
      several predictors based on clinical history and clinical presentation are
      related to the 10-year prognosis. They are more strongly associated with outcome
      among patients aged </=65 years. However, whether the patients have an AMI during
      the subsequent days will independently influence the long-term prognosis from
      observations on admission.

PMID- 11579353
TI  - Chlamydia pneumoniae and cytomegalovirus seropositivity, inflammatory markers,
      and the risk of myocardial infarction at a young age.
AB  - BACKGROUND: Pathogens causing chronic infections may promote atherosclerosis. The
      aim of our study was to evaluate the association of Chlamydia pneumoniae (Cp) and
      cytomegalovirus (CMV) infection and of inflammatory activation with premature
      myocardial infarction (MI). METHODS: Specific anti-Cp and anti-CMV immunoglobulin
      G (IgG), fibrinogen, white blood cells (WBC), and C-reactive protein (CRP) were
      measured in 120 post-MI patients </=50 years old and in 120 age-matched controls.
      RESULTS: Seropositivity to Cp and elevated concentrations of anti-Cp and anti-CMV
      IgGs were more frequent (P =.01) in patients than in control subjects, and
      fibrinogen, CRP, and WBC levels (P =.02) were more elevated. After adjustment for
      coronary risk factors and socioeconomic status, the odds ratios (95% confidence
      intervals) for premature MI were 2.4 (1.3-4.6) for Cp infection and 2.9 (1.5-5.8)
      for CMV. The risk of Cp infection was greater in smokers (3.7, 1.8-7.6). When
      both infections were present (35% of patients vs 8% of controls, P =.001), CRP
      was higher (P =.01) and the risk increased by 12 times (12.5, 4-38.9) compared
      with that in subjects without any infection and by 5 times (4.9, 2.2-10.9) if
      only one was present. CONCLUSIONS: After adjustment for confounders,
      seropositivity to both Cp and CMV infections is associated with the diagnosis of
      premature MI. The combination of both infections is associated with an enhanced
      inflammatory response and a markedly increased risk of premature MI.

PMID- 11579354
TI  - Short-term oral estrogen replacement therapy does not augment endothelium
      independent myocardial perfusion in postmenopausal women.
AB  - OBJECTIVES: The purpose of this study was to determine the effect of usual-dose
      estrogen replacement therapy (ERT) on myocardial perfusion and myocardial
      perfusion reserve (MPR) (evoked by an endothelium-independent vasodilator) in
      healthy postmenopausal women. Postmenopausal women have a decreased myocardial
      perfusion reserve compared with younger women. Estrogen infusions are known to
      enhance endothelium-dependent vasodilation of the epicardial coronary arteries in
      postmenopausal women, but whether ERT also enhances endothelium-independent
      myocardial perfusion and perfusion reserve is unclear. METHODS: In 24 healthy
      postmenopausal women who were not taking ERT, myocardial perfusion at rest,
      perfusion during the infusion of adenosine (a primarily endothelium-independent
      vasodilator), and MPR were determined by positron-emission tomography (PET) and
      oxygen 15-labeled water. The women were then randomly assigned in a double-blind
      fashion to receive either 0.625 mg of oral conjugated estrogens (Premarin) or
      placebo per day for 4 to 6 weeks, after which they underwent a repeat cardiac PET
      study. RESULTS: There was no statistical difference between those assigned to ERT
      and those assigned to placebo in the measurement of myocardial perfusion at rest
      (1.21 +/- 0.31 vs 1.16 +/- 0.18 mL/g/min, respectively) in response to adenosine
      (2.66 +/- 0.96 vs 3.3 +/- 0.45 mL/g/min) or MPR (2.24 +/- 0.83 vs 2.88 +/- 0.64
      mL/g/min) after 4 to 6 weeks of oral ERT. There was also no difference between
      the groups in any of the myocardial perfusion measurements after correction for
      the rate-pressure product. CONCLUSIONS: Short-term oral ERT does not affect
      myocardial perfusion at rest in response to adenosine or MPR in healthy
      postmenopausal women. Thus potential beneficial effects of ERT on vasomotor
      function may be limited to enhancement of endothelium-dependent vasodilative
      mechanisms affecting conduit vessels.

PMID- 11579355
TI  - Economic assessment of rheolytic thrombectomy versus intracoronary urokinase for
      treatment of extensive intracoronary thrombus: Results from a randomized clinical
      trial.
AB  - BACKGROUND: Despite advances in mechanical and pharmacologic therapy, thrombus
      containing lesions are at high risk for adverse events and remain a challenging
      subset for percutaneous coronary revascularization. Recently, rheolytic
      thrombectomy with the AngioJet device has been shown to safely remove
      intracoronary thrombus, but the overall cost-effectiveness of this technique is
      unknown. METHODS: We determined in-hospital and 1-year follow-up costs for 349
      patients with overt intracoronary thrombus who were randomly assigned to
      treatment with intracoronary urokinase (6- to 30-hour infusion followed by
      definitive revascularization; n = 169) or immediate thrombectomy with the
      AngioJet device (n = 180) as part of the Vein Graft AngioJet Study (VeGAS) 2
      trial. Catheterization laboratory costs were based on measured resource
      utilization and 1998 unit costs, whereas all other costs were estimated from
      hospital charges and cost center-specific cost-to-charge ratios. RESULTS:
      Compared with urokinase, rheolytic thrombectomy reduced the incidence of
      periprocedural myocardial infarction (12.8% vs 30.3%, P <.001) and major
      hemorrhagic complications (2.8% vs 11.2%, P <.001) and shortened length of stay
      by nearly 1 day (4.2 vs 4.9 days; P =.02). As a result, AngioJet treatment
      reduced procedural costs, hospital room/nursing costs, and ancillary costs with
      resulting hospital cost savings of approximately $3500 per patient during the
      initial hospitalization ($15,311 vs $18,841, P <.001). These cost savings were
      maintained at 1 year of follow-up ($24,389 vs $29,109, P <.001). CONCLUSIONS:
      Compared with standard treatment with intracoronary urokinase, rheolytic
      thrombectomy both improves clinical outcomes and reduces overall medical care
      costs for patients with extensive intracoronary thrombus.

PMID- 11579356
TI  - Hematocrit and the risk of coronary heart disease mortality.
AB  - BACKGROUND: An association between hematocrit (Hct) and coronary heart disease
      (CHD) mortality has been previously observed. However, the relationship of Hct
      and CHD independent of other cardiovascular disease (CVD) risk factors and
      differences between men and women remain unclear. METHODS: We examined the
      association between Hct and CHD mortality with Cox regression analyses of data
      from 8896 adults, aged 30-75 years, in the Second National Health and Nutrition
      Examination Survey (NHANES II) Mortality Study (1976-1992). Covariates included
      age, sex, race, education, smoking status, hypertensive status, total serum
      cholesterol, body mass index, white blood cell count, and history of CVD and
      diabetes. Hct was categorized by use of sex-specific tertiles, and all analyses
      were stratified by sex. RESULTS: During 16.8 years of follow-up, there were 545
      (men 343, women 202) deaths from CHD (International Classification of Diseases,
      9th revision [ICD-9] 410-414), 778 (men 426, women 279) deaths from diseases of
      the heart (ICD-9 390-398, 402, 404, 410-414, 415-417, 420-429), and 2046 (men
      1216, women 830) all-cause deaths. Among men, the crude CHD mortality rate per
      10,000 population was 42.6, 31.9, and 46.3 among those with Hct in the lower,
      middle, and upper tertiles, respectively. The corresponding crude CHD mortality
      rates among women were 12.6, 18.6, and 27.7. After adjustment for age and other
      CVD risk factors, there was no association between Hct in the upper tertile
      compared with the lower tertile and mortality from either CHD, diseases of the
      heart, or all causes among men. Women with Hct in the upper tertile were 1.3
      times (95% CI 0.9-1.9) more likely to die from CHD than were women with Hct in
      the lowest tertile, after multivariate adjustment. The effect of high Hct on CHD
      mortality among women younger than 65 years of age was slightly stronger
      (relative risk 2.2, 95% CI 1.0-4.6). CONCLUSIONS: These results suggest that the
      association between Hct and mortality from CHD and all causes is complex,
      differing both by sex and age. Further research is needed to gain a better
      understanding of these age and sex differences.

PMID- 11579357
TI  - Influence of isoproterenol on the accelerated junctional rhythm observed during
      radiofrequency catheter ablation of atrioventricular nodal slow pathway
      conduction.
AB  - BACKGROUND: Accelerated junctional rhythm (AJR) has been considered as a
      sensitive but rather nonspecific marker of successful radiofrequency (RF)
      ablation of slow pathway in patients with atrioventricular nodal reentrant
      tachycardia (AVNRT). However, AJR also occurs commonly during isoproterenol
      infusion. We therefore investigated the effect of isoproterenol on the
      significance of AJR while attempting slow pathway ablation. METHODS: Forty
      patients with AVNRT underwent slow pathway ablation. Sixty-nine RF applications
      accompanied by AJR were observed and were separated into 2 groups: applications
      performed without (group I, n = 26) and with (group II, n = 43) isoproterenol
      infusion. The specificity of AJR for successful ablation for each group was
      calculated. RESULTS: The specificity of AJR in groups I and II was 73% (19/26)
      and 49% (21/43), respectively (P <.05). There was no significant difference
      between the groups in the atrial electrogram width, atrial/ventricular
      electrogram amplitude ratio, the time from application onset to AJR emergence, or
      AJR cycle length. The catheter-tip temperature at AJR emergence was significantly
      lower (47 degrees C +/- 3 degrees C vs 52 degrees C +/- 3 degrees C, P <.001) and
      the ratio of junctional beats to total heart beats during RF application was
      significantly greater (46% +/- 24% vs 33% +/- 18%, P <.05) in group II compared
      with group I. CONCLUSIONS: Isoproterenol lowers the threshold of AJR emergence
      during RF application and thereby lowers the specificity of AJR for successful
      ablation. Complete washout of isoproterenol may therefore improve the specificity
      of AJR during RF ablation in patients with AVNRT.

PMID- 11579358
TI  - Longer longitudinal atrial dimension in patients with idiopathic paroxysmal
      atrial fibrillation: A possible cause of atrial fibrillation.
AB  - BACKGROUND: The ostium of the superior pulmonary veins or superior vena cava has
      been reported to be an important source of the ectopic beats that initiate
      paroxysmal atrial fibrillation (PAF). The structural details of the atria in
      patients with idiopathic PAF, however, remain unknown. METHODS: We studied 113
      patients (92 men and 21 women) with idiopathic PAF and 128 normal control
      subjects (100 men and 28 women). None of the subjects in either group were found
      to have any evidence of structural cardiac disease. The echocardiographic
      measurements were performed in the apical 4-chamber view during end-systole of
      sinus rhythm. RESULTS: The longitudinal dimension of the left and right atria was
      longer in patients with PAF who were not administered any drugs (non-drug-taking
      patients) than in the control subjects (P <.001 and P <.01, respectively).
      However, there were no significant differences in the transverse dimension of
      either atrium between such patients and control subjects. The longitudinal and
      transverse dimensions and volume determinations of atria were greater in the
      patients with idiopathic PAF who were administered class 1 antiarrhythmic drugs
      than in non-drug-taking patients (P <.05 to.001). In non-drug-taking patients,
      prolongation of the atrial longitudinal dimension did not depend on either age,
      the total frequency of PAF, or the interval from the first episode of PAF. The
      longitudinal dimension of the left and right atria was longer even in the
      patients with a short history of PAF (<1 month) as compared with control subjects
      (P <.001 and.05, respectively). CONCLUSIONS: These observations suggest that
      there is prolongation of the longitudinal dimension in patients with idiopathic
      PAF independent of PAF frequency and age (and that PAF is probably a consequence
      of the prolongation).

PMID- 11579359
TI  - First experience with hybrid percutaneous transmyocardial laser revascularization
      and angioplasty in patients with lesions at high risk for restenosis: Results of
      a phase I feasibility study.
AB  - BACKGROUND: Prior studies have suggested that percutaneous transmyocardial laser
      revascularization (PTMR) may be effective as a sole treatment modality in
      reducing angina in patients with severe coronary artery disease and no
      revascularization alternatives. The safety and efficacy of the hybrid or
      adjunctive use of PTMR during the same procedure as percutaneous intervention
      (PCI) has not previously been reported. METHODS: A US phase I feasibility study
      was therefore performed to determine whether PTMR performed in the same
      myocardial territory as PCI is able to ameliorate symptomatic recurrence from
      restenosis. RESULTS: After successful and uncomplicated PCI in 26 patients with
      class III-IV angina and lesion(s) at high risk for restenosis, PTMR was performed
      in the same myocardial territories subtended by the treated vessel(s). Major
      periprocedural adverse events (death, Q-wave myocardial infarction, and bypass
      surgery) occurred in 3 (11.5%) patients, as the result of subacute vessel closure
      in 2 patients, and tamponade in the third. Cumulative 6-month mortality rate was
      19.2%, including 2 late deaths between 3 and 4 months after discharge (1 death
      caused by late stent closure and 1 unexplained death during sleep.) Late repeat
      revascularization for restenosis in the PCI plus PTMR treated target vessel was
      required in 19.2% of patients, and an additional 11.5% of patients had class III
      IV angina at 6-month follow-up. CONCLUSIONS: These data demonstrate that in a
      patient population at high risk for restenosis, recently created PTMR channels
      are not protective against severe ischemia caused by acute vessel closure and
      that late symptomatic restenosis after PCI may still frequently occur despite
      PTMR in the same region.

PMID- 11579360
TI  - Direct infarct artery stenting without predilation and no-reflow in patients with
      acute myocardial infarction.
AB  - BACKGROUND: In patients with acute myocardial infarction (AMI), the rate of
      microvascular embolization and no-reflow promoted by coronary stenting with the
      use of conventional techniques (CS) appears to be greater than the one that
      occurs with balloon angioplasty. The minor invasiveness of direct stenting (DS)
      of the infarct artery without predilation could be expected to reduce
      embolization in the coronary microvasculature and no-reflow in patients with AMI.
      METHODS: In a cohort of 423 consecutive patients with AMI who underwent infarct
      artery stenting, we compared CS and DS in terms of angiographic no-reflow rate
      and 1-month clinical outcome. RESULTS: At baseline patients who underwent DS (n =
      110) had a better risk profile compared with the use of CS (n = 313). The
      incidence of angiographic no-reflow was 12% in the CS group and 5.5% in the DS
      group (P =.040). The 1-month mortality rate was 8% in the CS group and 1% in the
      DS group (P =.008). The mortality rate was 11% in patients with no-reflow and
      5.6% in patients with a normal flow. Multivariate analysis showed that age,
      preprocedure patent infarct artery, and lesion length were related to the risk of
      no-reflow. In the subset of patients with a target lesion length </=15 mm, the
      variables independently related to the risk of no-reflow were age, DS, and final
      balloon inflation pressure. CONCLUSIONS: DS in patients with AMI may reduce the
      incidence of angiographic no-reflow, thereby increasing ultimate effective
      myocardial reperfusion.

PMID- 11579361
TI  - Increased heterogeneity of coronary perfusion in patients with early coronary
      atherosclerosis.
AB  - BACKGROUND: In patients with typical angina but angiographically normal coronary
      arteries, abnormal vasomotor function is assumed to be a major underlying cause.
      However, data on this issue are conflicting, and recent studies suggest that
      fluid dynamic abnormalities exist in these patients. The aim of the study was to
      evaluate whether early stages of atherosclerosis are characterized by alterations
      of baseline coronary hemodynamics and endothelium-independent vasomotion. Besides
      established intracoronary Doppler parameters, heterogeneity of perfusion was
      assessed and related to early signs of atherosclerosis as determined by electron
      beam computed tomography (EBCT). METHODS: In 59 patients with typical angina and
      angiographically normal or near-normal coronary arteries, intracoronary Doppler
      measurements were performed in all 3 major coronary arteries. Baseline average
      peak velocity (bAPV) and hyperemic average peak velocity (hAPV) in response to
      intracoronary injection of adenosine were measured, and coronary flow velocity
      reserve (CFVR) was calculated. Heterogeneity was assessed as variability of bAPV,
      hAPV, and CFVR and was calculated as (STD/MEAN). 100. Doppler data were analyzed
      according to tertiles of the EBCT-derived Agatston calcium score (ie, score 0-1
      [lowest tertile], 2-28 [medium tertile], and >28 [highest tertile]). RESULTS: The
      mean EBCT-derived Agatston calcium score was 49 +/- 107. No coronary calcium was
      observed in 17 (29%) patients. The mean values of bAPV, hAPV, and CFVR were not
      different between the calcium score tertiles. However, patients in the highest
      tertile had a significantly increased variability index of bAPV (29.6% +/- 11.6%)
      compared with patients in the lowest tertile (13.4% +/- 7.3%, P <.0001).
      Variability of CFVR was also increased in these patients (15.5% +/- 11.7% vs
      10.5% +/- 4.0%, P =.03). CONCLUSION: These results indicate that early stages of
      atherosclerosis are characterized by microvascular abnormalities that do not
      uniformly affect the myocardium but are heterogeneous. The high variability of
      baseline coronary flow velocity with increasing coronary calcium suggests that in
      patients with early stages of atherosclerosis fluid dynamic effects may play a
      crucial role even in the absence of angiographically appreciable epicardial
      stenoses.

PMID- 11579362
TI  - Reliability, validity, and responsiveness of the six-minute walk test in patients
      with heart failure.
AB  - BACKGROUND: Our purpose was to evaluate the reliability, validity, and
      responsiveness of the 6-minute walk test (6MWT) in patients with heart failure
      (HF) enrolled in the Randomized Evaluation of Strategies for Left Ventricular
      Dysfunction (RESOLVD) pilot study. METHODS: A total of 768 patients was enrolled
      in a multicenter randomized clinical trial evaluating the effect of candesartan,
      enalapril, and metoprolol on left ventricular ejection fraction (LVEF), 6MWT
      distance, neurohormones, and quality of life. The 6MWT was performed once at
      screening and twice at baseline, 18 weeks, and 43 weeks by a standardized method.
      RESULTS: Test-retest reliability at baseline (intraclass correlation coefficient
      [ICC] = 0.90), 18 weeks (ICC = 0.88), and 43 weeks (ICC = 0.91) was very good.
      Baseline 6MWT distance was weakly inversely correlated to the quality-of-life
      cumulative score (r = -0.26, P =.0001) and moderately inversely correlated to the
      New York Heart Association functional classification (NYHA-FC) (r = -0.43, P
      =.001). In the RESOLVD study, the 6MWT was not responsive to change when effect
      sizes and standardized response means were used. Disease-specific quality of life
      was responsive to change in patients treated with candesartan and enalapril and
      NYHA-FC was responsive to change in the candesartan and enalapril combination and
      for enalapril alone with small effect sizes. The 6MWT, NYHA-FC, and quality of
      life were not responsive to change during the metoprolol or placebo phase.
      CONCLUSIONS: The 6MWT is highly reproducible in patients with symptoms of HF. It
      is somewhat correlated to NYHA-FC and quality of life. Overall, quality of life
      was most responsive to change, whereas 6MWT and NYHA-FC were comparable but less
      responsive to change in the RESOLVD study.

PMID- 11579363
TI  - Regression of left ventricular remodeling in chronic heart failure: Comparative
      and combined effects of captopril and carvedilol.
AB  - BACKGROUND: This study evaluated the independent and combined effects of
      captopril and carvedilol on left ventricular remodeling in chronic heart failure.
      Although angiotensin-converting enzyme inhibitors and b-blockers are known to
      attenuate the remodeling process in chronic heart failure, a direct comparison of
      these agents has not been performed. METHODS: We investigated 57 patients with
      mild to moderate chronic heart failure (48 ischemic, 9 nonischemic) who were
      randomized in a double-blind fashion to treatment with carvedilol or captopril at
      maximum doses of 25 mg twice daily for 3 months, followed by 3 months of combined
      treatment. Serial echocardiography, right heart catheterization, and treadmill
      exercise testing were performed at baseline, 3 months, and 6 months. After
      exclusions, 49 patients were evaluated during monotherapy and 48 during
      combination therapy. RESULTS: Carvedilol monotherapy produced significant
      reductions in end-systolic volume, leading to a greater median increase in
      ejection fraction compared with captopril monotherapy (4.7% vs 1.5%,
      respectively; P <.05). Each drug caused similar reductions in left ventricular
      mass, chamber sphericity, and pulmonary artery wedge pressure during monotherapy
      and combined treatment. Adjunctive treatment with carvedilol produced a trend
      toward a greater increase in ejection fraction (4.3% vs 2.7%, respectively; P not
      significant) and significantly greater reductions in the wall thickening score
      index than with captopril (0.25 vs 0.08, respectively; P =.04). CONCLUSIONS:
      Although angiotensin-converting enzyme inhibitor therapy did not alter left
      ventricular volume, treatment with carvedilol was associated with reductions in
      chamber volume; both drugs reduced left ventricular mass and sphericity. These
      beneficial effects on remodeling may help to explain the relative prognostic
      benefits of these therapies.

PMID- 11579364
TI  - Outcomes after emergency department discharge with a primary diagnosis of heart
      failure.
AB  - BACKGROUND: Patients with decompensated chronic heart failure (CHF) are
      frequently evaluated in emergency departments (ED). The outcomes of such patients
      after discharge to the outpatient setting from the ED are not well known. Risk
      factors for return ED visits or subsequent hospital admission after ED discharge
      for CHF also are not known. METHODS: Charts were reviewed from all 112 patients
      discharged from the Parkland Memorial Hospital ED with a primary diagnosis of CHF
      from October to December 1998. A composite end point ("failure of outpatient
      therapy") was prespecified to be a recurrent ED visit for CHF, hospitalization
      for CHF, or death at 3 months after the index ED discharge. RESULTS: Within 3
      months of the index ED visit, 61% of the study population met the composite end
      point. The median time to failure of outpatient therapy was 30 days. Univariate
      analysis of 27 clinical and demographic variables demonstrated the respiratory
      rate at presentation as the only predictor of failure of outpatient therapy (P
      =.02). Multivariate analysis of a model with 8 prespecified variables also
      demonstrated respiratory rate to be the only variable independently associated
      with an increased risk for the composite end point (odds ratio 1.6, 95%
      confidence interval 1.1-2.6, for each increase of 5 breaths/min). CONCLUSION:
      There is a high rate of failure of outpatient therapy (61%) in patients
      discharged with a primary diagnosis of CHF from an urban county hospital ED.
      Increased respiratory rate on presentation to the ED may be associated with
      adverse outcomes after ED discharge for CHF.

PMID- 11579365
TI  - Several factors associated with the insulin resistance syndrome are predictors of
      left ventricular systolic dysfunction in a male population after 20 years of
      follow-up.
AB  - BACKGROUND: The epidemiologic data on heart failure are scarce. This study aimed
      at identifying predictors of left ventricular systolic dysfunction in a cohort of
      middle-aged men with a 20-year follow-up. METHODS: A population-based cohort of
      431 50-year-old men was examined with blood pressure and anthropometric
      measurements together with lipid, glucose, and insulin determinations. A
      reinvestigation 20 years later also included echocardiography, ambulatory blood
      pressure monitoring, hyperinsulinemic euglycemic clamp, and oral glucose
      tolerance test. Sixteen subjects were found to have left ventricular systolic
      dysfunction at age 70 years, defined as an ejection fraction </=0.40. A control
      group of 48 subjects matched on myocardial infarction, hypertension, diabetes,
      and use of cardiovascular medication, but with an ejection fraction >0.40, was
      used in a nested case-control analysis. RESULTS: At age 50 years, heart rate (P
      <.01), plasma proinsulin (P <.05), and the proportion of dihomogammalinolenic
      acid in serum cholesterol esters (P <.05) were increased and serum phosphate
      decreased (P <.01) in the subjects identified with left ventricular systolic
      dysfunction at age 70 years compared with controls. No major metabolic
      abnormalities were associated with left ventricular systolic dysfunction at age
      70 years compared with controls. CONCLUSION: Factors associated with insulin
      resistance precede left ventricular systolic dysfunction independently of
      ischemic heart disease and hypertension after 20 years of follow-up.

PMID- 11579366
TI  - Natriuretic peptides in patients with aortic stenosis.
AB  - BACKGROUND: Whereas atrial natriuretic peptide (ANP) is secreted mainly from
      cardiac atria, brain natriuretic peptide (BNP) is produced to a larger extent in
      ventricles. Their relative importance as markers of cardiac function and
      myocardial hypertrophy is not yet clarified. This study evaluated circulating BNP
      and ANP and the N-terminal part of their propeptides (NT-proBNP and NT-proANP) as
      markers of left ventricular hypertrophy and atrial pressure increase in patients
      with aortic stenosis. METHODS: The plasma concentrations of BNP, NT-proBNP, ANP,
      and NT-proANP were measured by radioimmunoassay in 67 patients with aortic
      stenosis. Peptide plasma concentrations were related to measurements obtained by
      cardiac catheterization and echocardiography. RESULTS: Receiver operating
      characteristic curves indicated that BNP and NT-proBNP performed best in the
      detection of increased left ventricular mass and NT-proANP in the detection of
      increased left atrial pressure. NT-proBNP was significantly increased in mild
      left ventricular hypertrophy (left ventricular mass index, 78 to 139 g/m(2)),
      whereas NT-proANP was not increased until left ventricular mass index was 141 to
      180 g/m(2). CONCLUSIONS: Plasma BNP and NT-proBNP may serve as early markers of
      left ventricular hypertrophy, whereas ANP and NT-proANP reflect left atrial
      pressure increase. The repeated and combined measurements of natriuretic peptides
      might provide diagnostic information relevant to the evaluation of the stage of
      aortic stenosis.

PMID- 11579367
TI  - Intravenous prostaglandin E1 reduces soluble vascular cell adhesion molecule-1 in
      peripheral arterial obstructive disease.
AB  - OBJECTIVES: Elevated levels of soluble (s) vascular cell adhesion molecule-1
      (VCAM-1) and intercellular adhesion molecule-1, pointing to activation of cells
      involved in vascular inflammation, have been previously reported in peripheral
      arterial obstructive disease (PAOD). We tested the hypothesis that intravenous
      prostaglandin E(1) (PGE(1)) treatment, which produces clinical benefits in this
      condition, might decrease such levels. METHODS: Ten subjects (age range 58 +/- 10
      years, 6 male, 4 female) with characterized Fontaine stage IIa to IV PAOD
      (ankle/arm pressure index <0.96) were entered into a treatment protocol with
      twice daily intravenous infusions of PGE(1) (alprostadil) at 120 microg per day,
      repeated for 10 consecutive days. Preinfusion and postinfusion plasma samples
      were stored for blind enzyme immunoassays of soluble adhesion molecules and the
      fibrinolytic marker tissue plasminogen activator, type-1 plasminogen-activator
      inhibitor, and D -dimer. RESULTS: Estimates of severity of pain at rest,
      consumption of analgesics, magnitude of trophic lesions, remission to lower
      Fontaine stages, and favorable changes in the venoarteriolar reflex documented
      significant beneficial effects of the treatment. Significant (P <.01)
      pretreatment and posttreatment reductions of in all soluble markers explored were
      found. Particularly, sVCAM-1 exhibited a significant decrease after each
      infusion, which was sustained at the last day of treatment (from 854 +/- 214
      ng/mL to 775 +/- 215 ng/mL across the first infusion, from 773 +/- 146 ng/mL to
      680 +/- 110 ng/mL across the last infusion). CONCLUSION: Thus a global decrease
      of vascular cell activation appears to occur as a result of PGE(1) administration
      and may contribute to the observed clinical benefits in PAOD.

PMID- 11579368
TI  - Follow-up study of coronary artery bypass grafting in patients with Kawasaki
      disease.
AB  - BACKGROUND: The purpose of this study was to assess the long-term clinical
      outcome of coronary artery bypass grafting in pediatric patients with Kawasaki
      disease. METHODS: Six patients (mean age, 9.3 +/- 1.6 years) underwent coronary
      artery bypass grafting between September 1985 and December 1992. The number of
      bypass grafts placed was 1 to 2 per patient (mean 1.3 +/- 0.5). The left internal
      mammary artery (IMA) was used as a bypass graft in 3 patients, bilateral IMA in
      1, and saphenous vein in 3. All patients underwent postoperative evaluations
      after 1 month and between 5 and 10 years. RESULTS: Follow-up ranged between 9 and
      16 years (mean 12.6 +/- 2.7 years). Stress myocardial scintigraphy identified 2
      patients with transient ischemia, one of whom died suddenly after 16
      postoperative years. Coronary angiography demonstrated that the grafts of 5
      patients were patent at both the short- and long-term follow-up. However, in 1
      patient, the IMA that was grafted to the diagonal artery was occluded 1 month
      after surgery. Five survivors are in good health, without clinical angina.
      CONCLUSIONS: We consider that coronary revascularization with bilateral IMA
      grafts may provide a more favorable prognosis in patients with severe Kawasaki
      coronary artery disease. Stress myocardial scintigraphy and echocardiography can
      be used effectively to follow such patients.

PMID- 11579369
TI  - Effect of early treatment with captopril and metoprolol singly and together on
      postinfarction left ventricular remodeling.
AB  - BACKGROUND: beta-Blockers improve clinical outcome after acute myocardial
      infarction (AMI), but few data are available on their effectiveness in preventing
      left ventricular remodeling. The aim of the study was to assess the relative
      effects of captopril, metoprolol, and their combination on left ventricular
      remodeling after uncomplicated AMI. METHODS: Two hundred fifty consecutive
      patients with a first AMI were randomly allocated to receive for 6 months
      captopril (up to 75 mg/d, group 1), metoprolol (up to 200 mg/d, group 2), or both
      (group 3) starting within 24 hours from symptom onset. Of these, 130 patients
      (group 1, 46; group 2, 47; group 3, 37) completed the study; all patients
      underwent 2-dimensional echocardiography at baseline and after 2 weeks and 3 and
      6 months from AMI. RESULTS: At 6 months, in comparison with baseline values, left
      ventricular end-diastolic area index (LVEDI) significantly increased in group 3
      (P =.013) and wall motion score index significantly decreased in group 1 (P
      =.038). At any follow-up evaluation, the covariance analysis showed significantly
      greater interval changes in LVEDI in group 3 than in group 1 (P =.0077 at 2
      weeks, P =.0108 at 3 months, and P = 0.0155 at 6 months). No significant
      differences were observed between group 1 and group 2 and between group 2 and
      group 3. CONCLUSIONS: After uncomplicated first AMI, early and long-term
      treatment with captopril alone attenuates left ventricular remodeling better than
      its combination with metoprolol. In the head-to-head captopril versus metoprolol
      therapy strategy comparison, captopril alone seems more effective in reducing
      postinfarction enlargement, but a definite difference was not demonstrated.

PMID- 11579370
TI  - Tamoxifen is not detrimental to endothelial function in postmenopausal women with
      breast cancer.
AB  - BACKGROUND: Tamoxifen has mixed estrogen agonist and antagonist properties in
      estrogen-regulated tissues. Its effect on the cardiovascular system is not well
      defined. We carried out a study to investigate the effect of tamoxifen on
      peripheral vascular endothelial function. METHODS: Three groups of postmenopausal
      women (median age, 56 years; range, 39 to 69 years) with breast cancer were
      studied. Patients in group 1 (n = 10) were newly diagnosed with breast cancer and
      studied before and after 4 weeks treatment with tamoxifen. Group 2 women (n = 6)
      had been receiving long-term tamoxifen (3 to 5 years) and were studied while
      taking tamoxifen and 4 weeks after stopping it. The final group of 6 subjects
      were in remission from primary breast cancer and were not receiving or had
      previously received tamoxifen. Ultrasound assessments of endothelial function
      were done before and 4 weeks after the initiation or discontinuation of tamoxifen
      with the nontreatment group acting as control. All ultrasound imaging was made by
      a single investigator blinded to the therapeutic status of the subject. Brachial
      artery diameter was measured by ultrasound at baseline and 1 minute after
      reactive hyperemia. Flow-mediated reactivity (FMR) was defined as percent change
      in artery diameter from baseline 1 minute after reactive hyperemia. RESULTS:
      There was no change in FMR in patients before compared with 4 weeks after
      starting tamoxifen (4.06% +/- 1.44% vs 3.97% +/- 1.20%, respectively, mean +/-
      standard error of the mean [SEM], P =.97). There was no significant change in FMR
      on withdrawal from tamoxifen (1.84% +/- 1.98% vs -0.42% +/- 1.44% on tamoxifen vs
      off tamoxifen, mean +/- SEM, P =.36). FMR in subjects taking tamoxifen was no
      different from the control group (3.17% +/- 1.05% vs 3.16% +/- 0.91%,
      respectively, mean +/- SEM, P =.995). CONCLUSIONS: Tamoxifen does not appear to
      affect endothelial function in the short term in postmenopausal women with breast
      cancer.

PMID- 11579371
TI  - Medical and socioenvironmental predictors of hospital readmission in patients
      with congestive heart failure.
AB  - BACKGROUND: Patients with chronic congestive heart failure (CHF) require frequent
      rehospitalization because of the exacerbation of CHF. It is of clinical
      importance to determine predicting factors for readmission to reduce this
      likelihood. Previous studies have focused primarily on the demographic and
      medical characteristics in selected subsets of patients. Therefore, within a
      broad cohort of consecutively hospitalized patients, we sought to identify not
      only demographic and medical predictors but also socioenvironmental factors
      associated with readmission. METHODS: We assessed demographic (age, sex), medical
      (etiology of CHF, New York Heart Association functional class, left ventricular
      ejection fraction, previous admission for CHF, length of hospital stay,
      comorbidity, and medications), and socioenvironmental variables (occupation,
      financial resources, living alone, and follow-up visits) in 230 patients
      discharged with a diagnosis of CHF and recorded hospital readmission. RESULTS:
      Within 1 year after discharge, 81 patients (35%) were readmitted. Five variables,
      including poor follow-up visits (odds ratio [OR] 4.9, 95% CI 2.0-11.8), previous
      admission for CHF (OR 3.3, 95% CI 1.8-6.1), no occupation (OR 2.6, 95% CI 1.2
      5.5), longer hospital stay (OR 3.2, 95% CI 1.2-8.5), and hypertension (OR 2.0,
      95% CI 1.1-3.7), were identified as significant independent predictors for
      readmission by multivariate logistic regression analysis. CONCLUSIONS: Our
      independent predictors of readmission support the importance of medical and
      socioenvironmental factors in the deterioration of CHF. Therefore interventions
      to decrease readmission should also target social management in all hospitalized
      patients.

PMID- 11579372
TI  - [Gender-specific aspects in chronic low back pain rehabilitation].
AB  - Gender-specific Aspects in Chronic Low Back Pain Rehabilitation. Little is known
      about gender differences in utilisation, outcomes and evaluation of orthopaedic
      rehabilitation for chronic low back pain. The purpose of this article is to
      review and analyse the literature on rehabilitation and recovery of men and women
      with chronic back pain. In Western societies, chronic back pain is one of the
      most common causes for utilising medical rehabilitation services. In general no
      significant gender differences in the prevalences of back pain are found, but men
      are more sick-listed and early retired due to musculoskeletal diseases. Also,
      more men than women participate in medical rehabilitation programmes. National
      and international studies pinpoint the fact that differences exist between women
      and men with regard to participating in an orthopaedic rehabilitation programme.
      Additionally there is some evidence that different physical and psychological
      therapy services have different effects on health status of women and men. Mixed
      results are available regarding gender differences concerning the outcomes of
      rehabilitation programmes. Rehabilitation activities after discharge from in
      patient programmes and these being performed within the home setting are primary
      indicators of recovery. Gender differences have been identified regarding various
      types of activities, apparently because especially family roles interfere with
      activity. Further research must be conducted so as to increase the understanding
      of women's and men's experiences relative to orthopaedic diseases and orthopaedic
      rehabilitation services.

PMID- 11579373
TI  - ["Zest for life instead of strain of illness" - implementation and evaluation of
      a programme activating chronic back pain patients in a rehabilitation clinic].
AB  - "Zest for Life Instead of Strain of Illness" - Implementation and Evaluation of a
      Programme Activating Chronic Back Pain Patients in a Rehabilitation Clinic.A
      group training was developed for chronic back pain patients in a rehabilitation
      clinic to enhance coping, to activate internal and external resources, and to
      make transfer to everyday life easier. The training consists of 12 either
      physiotherapeutic or psychologically oriented sessions. The training was
      evaluated in a longitudinal, quasi-experimental control-group design. Patients of
      the intervention group (n = 144) and control group (n = 157) rated the usefulness
      of the rehabilitation for private and working life at the end of the in-patient
      phase (t1) and three month later (t2). They also evaluated selected elements of
      the rehabilitation (t2). Results show that the anticipated usefulness of the
      rehabilitation was rated higher at the end of the stay than three months later.
      This indicates frustration after returning to everyday life. Patients of the
      intervention group rated the transfer possibilities to working life higher than
      the control group. They also are more satisfied with the psychological parts of
      the rehabilitation. After minor revisions, such as strengthening the topic of
      employment, the training now is implemented in the clinic for all patients with
      chronic back pain.

PMID- 11579374
TI  - [Symptoms, effects on quality of life, judgement and expectations of treatment in
      active ankylosing spondylitis: the patient's view].
AB  - Symptoms, Effects on Quality of Life, Judgement and Expectations of Treatment in
      Active Ankylosing Spondylitis: The Patient's View.In ankylosing spondylitis
      uncertainty prevails among rheumatologists on how to define and measure activity.
      In the present study the patient's view of activity was evaluated. What does
      active ankylosing spondylitis mean for the patient? In a standardized interview
      the patient was asked to describe, from his own experience, what active
      ankylosing spondylitis means, what bothers him most, what helps most, and what he
      expects from therapy. For the patient, active ankylosing spondylitis means pain
      (99 responses), mobility restriction (19), muscle tension (10), inability to stay
      supine (6), restriction in chest mobility (5) and dyspnea (5). Fatigue was
      mentioned by two patients. In active states patients are mainly bothered by pain
      (77), mobility restriction (55), consequences for social life (20) and work (18),
      disturbed sleep (17) and difficult breathing (16). Drugs (84) and physical
      activity (42) were judged the best treatments during active ankylosing
      spondylitis. It was no surprise that pain and mobility restriction were cited
      most often by the patients. Breathing difficulties were cited rather often,
      whereas fatigue seems not to play an important role for most patients. The
      results suggest that modern rheumatology may have underestimated the relevance of
      difficult breathing and paid too much attention to fatigue.

PMID- 11579375
TI  - [Effects of treatment in mother-child rehabilitation centres].
AB  - Effects of Treatment in Mother-Child Rehabilitation Centres. The study aims at an
      external evaluation of mother-child rehabilitation centres in Germany. The
      centres taking part in the project will get detailed information about their
      present state of quality in the dimensions of structure, process and outcome as
      well as patient satisfaction and job satisfaction of the employees. This article
      focuses on quality of outcome. Two main questions are addressed: How do women
      treated in mother-child rehabilitation centres assess their health problems at
      admission, and what are the effects after three weeks of inpatient treatment? The
      results show that in comparison with a German norm population, 55 % to 75 % of
      the women in the present study reported intense distress in all dimensions of
      health (somatic, functional and psychosocial). The analysis of effects after
      treatment confirms a distinct improvement of health status reported by patients
      as well as by doctors and therapists. Data of a follow-up after 6 months will
      show whether these positive effects can be maintained.

PMID- 11579376
TI  - [Occupational choice and biography - biographical diagnostics as an approach to
      accessing the individual's perceptual horizons and resources in the context of
      vocational rehabilitation].
AB  - This contribution is focused on the core tenet that the process of choice of
      occupation must encompass in its everyday routines the disabled person's
      biography, his or her life experiences, biographical self-appraisals as well as
      action orientations. Unless this is achieved, its professional strategies and
      interventions will remain prone to missing, or even counteracting, the
      biographical resources as well as thinking and perceptions of its clients.
      Biographical Diagnostics is presented here as a method seeking to access the
      individual in the process of choice of occupation in an understanding manner. It
      constitutes a new concept in terms of a biography-based, hermeneutic case
      approach conceived for implementation in the everyday routines of vocational
      rehabilitation. Two case examples serve to explicate the method of Biographical
      Diagnostics and set out the relevancy of a biographical orientation in the
      process of occupational choice.

PMID- 11579377
TI  - [Reassessment - a system for comprehensive evaluation of work related capacity].

PMID- 11579378
TI  - Characterization of the central nervous system innervation of the rat spleen
      using viral transneuronal tracing.
AB  - Splenic immune function is modulated by sympathetic innervation, which in turn is
      controlled by inputs from supraspinal regions. In the present study, the
      characterization of central circuits involved in the control of splenic function
      was accomplished by injecting pseudorabies virus (PRV), a retrograde transynaptic
      tracer, into the spleen and conducting a temporal analysis of the progression of
      the infection from 60 hours to 110 hours postinoculation. In addition, central
      noradrenergic cell groups involved in splenic innervation were characterized by
      dual immunohistochemical detection of dopamine-beta-hydroxylase and PRV.
      Infection in the CNS first appeared in the spinal cord. Splenic sympathetic
      preganglionic neurons, identified in rats injected with Fluoro-Gold i.p. prior to
      PRV inoculation of the spleen, were located in T(3)-T(12) bilaterally; numerous
      infected interneurons were also found in the thoracic spinal cord (T(1)-T(13)).
      Infected neurons in the brain were first observed in the A5 region, ventromedial
      medulla, rostral ventrolateral medulla, paraventricular hypothalamic nucleus,
      Barrington's nucleus, and caudal raphe. At intermediate survival times, the
      number of infected cells increased in previously infected areas, and infected
      neurons also appeared in lateral hypothalamus, A7 region, locus coeruleus,
      subcoeruleus region, nucleus of the solitary tract, and C3 cell group. At longer
      postinoculation intervals, infected neurons were found in additional hypothalamic
      areas, Edinger-Westphal nucleus, periaqueductal gray, pedunculopontine tegmental
      nucleus, caudal ventrolateral medulla, and area postrema. These results
      demonstrate that the sympathetic outflow to the spleen is controlled by a complex
      multisynaptic pathway that involves several brainstem and forebrain nuclei.

PMID- 11579379
TI  - Stereological estimates of total neuron numbers in the hippocampus of adult
      reeler mutant mice: Evidence for an increased survival of Cajal-Retzius cells.
AB  - The cytoarchitecture of the brain is disrupted severely in reeler mice. This is
      caused by a deficiency in the protein, Reelin, which is essential for the normal
      migration and positioning of neurons during development. Although cell migration
      is clearly affected by the reeler mutation, it is believed that the total number
      of neurons is not. Thus, we were surprised to find an unusually large number of
      calretinin-immunopositive cells, presumably Cajal-Retzius cells, in the molecular
      layer of the adult reeler hippocampus (Deller et al. [1999]; Exp. Neurol. 156:239
      253). This suggested that the reeler mutation affects the number of neurons in
      the hippocampus. In order to verify this hypothesis, unbiased stereological
      methods were employed. Calretinin immunostaining was used as a marker for Cajal
      Retzius cells in control as well as reeler mice and Nissl staining was used to
      identify hippocampal principal neurons. Total numbers of calretinin
      immunopositive cells, calretinin-immunoreactive Cajal-Retzius cells, and Nissl
      stained neurons were estimated in different subfields of the reeler and the
      control hippocampus. Stereological estimates (P < 0.05) revealed that the total
      number of calretinin-immunopositive and Cajal-Retzius cells in reeler mice are
      1.5 and 2.1 times that of controls, respectively. No significant difference in
      total neuron number was found in any hippocampal subfield. These data demonstrate
      that the reeler mutation affects the number of calretinin-immunoreactive Cajal
      Retzius cells in the adult hippocampus, probably due to a reduced excitatory
      innervation by entorhinal terminals in the absence of reelin. However, the reeler
      mutation does not affect mechanisms that determine total hippocampal neuron
      number.

PMID- 11579380
TI  - Expression of growth differentiation factor-15/ macrophage inhibitory cytokine-1
      (GDF-15/MIC-1) in the perinatal, adult, and injured rat brain.
AB  - We and others have recently cloned a new member of the transforming growth factor
      beta superfamily, growth differentiation factor-15/ macrophage inhibitory
      cytokine-1 (GDF-15/MIC-1). Using in situ hybridization and immunohistochemistry,
      we determined the distribution of GDF-15/MIC-1 mRNA and protein in the perinatal
      and cryolesioned adult rat brain. The choroid plexus epithelium of all ventricles
      represents the site of strongest and almost exclusive mRNA expression in the
      normal perinatal and adult brain. The newborn rat brain reveals GDF-15/MIC-1
      immunoreactivity (ir) in ependymal cells lining the ventricles, in the striatal
      subventricular zone, and in populations of nonneural cells of the
      thalamic/hippocampal lamina affixa, in addition to that in the choroid plexus.
      Unilateral cryogenic cortical lesioning induced a significant increase of GDF
      15/MIC-1 mRNA expression and ir at the lesion site and expression in presumed
      neurons within the dorsal thalamic area. At the lesion site, GDF-15/MIC-1
      producing cells showed immuncytochemical features of neurons, macrophages, and
      activated microglial cells. Fluorescent microscopy revealed both intra- and
      extracellular GDF-15/MIC-1 ir. Up-regulation of GDF-15/MIC-1 in activated
      macrophages (Mstraight phi) is also supported by RT-PCR, ICC, and Western blot
      experiments showing pronounced induction of GDF-15/MIC-1 expression (mRNA and
      protein) in retinoic acid/phorbol ester-stimulated human M phi. Our data suggest
      that 1) GDF-15/MIC-1 is secreted into the cerebrospinal fluid and 2) in the
      newborn brain may penetrate through the ependymal lining and act on developing
      neurons and/or glial cells. As a constituent of cells in the lamina affixa, the
      protein might be involved in the regulation of mesenchyme-epithelial
      interactions. Finally, GDF-15/MIC-1 may also act within the antiinflammatory
      cytokine network activated in CNS lesions.

PMID- 11579381
TI  - Differential gene expression of adenosine A1, A2a, A2b, and A3 receptors in the
      human enteric nervous system.
AB  - Adenosine receptors (ADORs) in the enteric nervous system may be of importance in
      the control of motor and secretomotor functions. Gene expression and distribution
      of neural adenosine A1, A2a, A2b, or A3 receptors (Rs) in the human intestine was
      investigated using immunochemical, Western blotting, RT-PCR, and short-circuit
      current (I(sc)) studies. Adenosine A1R, A2aR, A2bR, or A3R mRNAs were
      differentially expressed in neural and nonneural layers of the jejunum, ileum,
      colon, and cecum and in HT-29, T-84, T98G, and Bon cell lines. A1R, A2aR, A2bR,
      and A3R immunoreactivities (IRs) were differentially expressed in PGP 9.5
      immunoreactive neurons. A2bR IR occurs exclusively in 50% of submucosal
      vasoactive intestinal peptide (VIP) neurons (interneurons, secretomotor or motor
      neurons) in jejunum, but not colon; A2aR is also found in other neurons. A3R IR
      occurs in 57% of substance P-positive jejunal submucosal neurons (putative
      intrinsic primary afferent neurons) and less than 10% of VIP neurons. Western
      blots revealed bands for A3R at 44 kDa, 52 kDa, and 66 kDa. A2aR and A2bR are
      coexpressed in enteric neurons and epithelial cells. 5'-N
      methylcarboxamidoadenosine or carbachol evoked an increase in I(sc). A2bR IR is
      more prominent than A2aR IR in myenteric neurons, nerve fibers, or glia. A1R is
      expressed in jejunal myenteric neurons and colonic submucosal neurons. Regional
      differences also exist in smooth muscle expression of ADOR IR(s). It is concluded
      that neural and nonneural A1, A2a, A2b, and A3Rs may participate in the
      regulation of neural reflexes in the human gut. Clear cell and regional
      differences exist in ADOR gene expression, distribution, localization, and
      coexpression.

PMID- 11579382
TI  - Age-related decline of presumptive inhibitory synapses in the sensorimotor cortex
      as revealed by the physical disector.
AB  - The synapse, as the site of functional neural interaction, has been suggested as
      a possible substrate for age-related impairment of cognitive ability. Using the
      physical disector probe with tissue prepared for ultrastructural analysis, we
      find an age-related decline in the numerical density of presumptive inhibitory
      synapses in layer 2 of the sensorimotor cortex of the Brown Norway x Fisher 344
      rat. This age-related decline in presumptive inhibitory synapses is maintained
      when the density of synapses is combined with the numerical density of neurons
      quantified from the same anatomical space to arrive at a ratio of synapses per
      neuron. The numerical density of these synapses declines between middle-aged (18
      months) and old (29 months) animals by 36% whereas numerical density of neurons
      does not change between these ages, resulting in a decline in the ratio of
      presumptive inhibitory synapses per neuron in this cortical area. This study
      demonstrates a deficit in the intrinsic inhibitory circuitry of the aging
      neocortex, which suggests an anatomical substrate for age-related cognitive
      impairment.

PMID- 11579383
TI  - Distribution of cocaine- and amphetamine-regulated transcript peptide in the
      guinea pig intrinsic cardiac nervous system and colocalization with neuropeptides
      or transmitter synthetic enzymes.
AB  - This study was conducted to establish the presence of cocaine- and amphetamine
      regulated transcript peptide (CARTp) immunoreactivity in neurons and fibers
      within guinea pig atrial whole-mount preparations containing the intrinsic
      cardiac ganglia. Many cardiac ganglia, but not all, in a given whole-mount
      preparation, were innervated by CARTp-immunoreactive (IR) fibers. Following
      explant culture of whole mounts for 72 hours, the CARTp-IR fiber networks were
      absent, but the number of CARTp-IR neurons was increased markedly. These
      observations suggested that the majority of the CARTp-IR fibers in the
      intracardiac ganglia were derived from sources extrinsic to the heart. In control
      whole-mount preparations, very few CARTp-positive neurons were present. The few
      intrinsic CARTp-IR neurons also exhibited choline acetyltransferase (ChAT)
      immunoreactivity, indicating that they make up a small subpopulation of
      cholinergic postganglionic neurons. Some CARTp-IR neurons also exhibited nitric
      oxide synthase (NOS) immunoreactivity, indicating that they were nitrergic as
      well. We compared the immunohistochemical staining patterns of CARTp-IR fibers
      with the staining patterns of a number of other neurotransmitters or
      neurotransmitter synthetic enzymes that mark specific extrinsic inputs. The CARTp
      IR fibers were not immunoreactive for ChAT, tyrosine hydroxylase, calcitonin gene
      related peptide, or substance P. However, virtually all CARTp-IR fibers exhibited
      immunoreactivity to neuronal NOS (a marker for nitric oxide-producing neurons).
      CARTp-IR cells and NOS-IR cells were present in the nodose ganglia. In addition,
      CARTp-IR neurons in the nodose also were stained positively for NADPH-diaphorase.
      Thus, we propose that most CARTp-IR fibers within the guinea pig intrinsic
      cardiac ganglia are vagal afferent fibers that also contain NOS.

PMID- 11579384
TI  - Organization of corticostriatal projections from the vibrissal representations in
      the primary motor and somatosensory cortical areas of rodents.
AB  - To characterize corticostriatal projections from rodent sensorimotor cortex, the
      anterograde tracers biotinylated dextran amine (BDA) and fluororuby (FR) were
      injected into the whisker representations of the primary motor (MI) and
      somatosensory (SI) cortices. Reconstructions of labeled terminals and their
      beaded varicosities in the neostriatum and thalamus were analyzed quantitatively
      to determine the degree of labeled overlap in both of these subcortical
      structures. Corticostriatal projections from the vibrissal representation in MI
      were more extensive than corresponding projections from SI. Both cortical areas
      sent dense projections to the dorsolateral neostriatum, but the MI vibrissal
      representation also projected to regions located more rostrally and medially.
      Despite these differences, both MI and SI projected to overlapping parts of the
      dorsolateral neostriatum. Tracer injections in both cortical areas also produced
      dense anterograde and retrograde labeling in the medial sector of the posterior
      complex of the thalamus (POm). Because POm is somatotopically organized and has
      reciprocal connections with both SI and MI cortices, the amount of labeled
      overlap in POm was used to indicate whether the tracers were injected into
      corresponding whisker representations of MI and SI. We found that the proportion
      of labeled overlap in the neostriatum was highly correlated with the amount of
      labeled overlap in POm. These results indicate that the rodent neostriatum
      receives convergent projections from corresponding regions in MI and SI cortex.
      Furthermore, the thalamocortical projections of the POm indicate that it may
      modulate corticostriatal outputs from corresponding representations in MI and SI.

PMID- 11579385
TI  - Pros and cons of mammographic screening.

PMID- 11579386
TI  - Complications and functional evaluation of 17 saddle prostheses for resection of
      periacetabular tumors.
AB  - Seventeen saddle prostheses were inserted between 1988 and 1997 after resection
      of periacetabular tumors. The tumors involved the zones II and III of Enneking
      classification in 13 patients, the zones I and II in 2 patients, and the zone II
      in 2 patients. The tumors included 11 chondrosarcomas, 3 Ewing sarcomas, 2 giant
      cells tumors, and 1 metastasis of renal carcinoma. The tumoral resection was wide
      "en bloc" in 14 cases, marginal in 2 cases, and intratumoral in 1 case. The mean
      follow-up period of the patients is 42 months ranging from 8 to 84 months. Local
      recurrences occurred in five cases and metastases in four cases. Five patients
      died of tumoral disease and one of intercurrent disease. Complications were
      observed in 11 cases (65%) including nerve damages (3 cases), deep infections (3
      cases), upward migrations of the saddle (4 cases), saddle dislocations (3 cases),
      sacroiliac subluxations (2 cases), and mechanical failures (2 cases). The
      modified Musculoskeletal Tumor Society Score (MSTS) and the Toronto Extremity
      Salvage Score (TESS) were used for functional analysis. Functional results were
      available for only nine patients of the series with a mean MSTS of 17 points
      ranging from 11 to 23 points and a mean TESS of 58 points ranging from 39 to 95
      points. The saddle prosthesis provided in all cases of this series an early
      painfree weight-bearing reconstruction with minimal limb shortening, but the
      functional results remained fair in most patients due to a limited range of
      motion and a poor abductor strength.

PMID- 11579387
TI  - Correlation of human papillomavirus 16 and 18 with cervical neoplasia in
      histological typing and clinical stage in Taiwan: an in-situ polymerase chain
      reaction approach.
AB  - BACKGROUND AND OBJECTIVES: In situ polymerase chain reaction (ISPCR) promises to
      considerably enhance our ability to detect a few copies of target nucleic acid
      sequences in fixed tissues and cells. The aim of this study was to investigate
      cervical carcinoma to determine the human papillomavirus (HPV) types on paraffin
      embedded tissue sections by ISPCR and standard in situ hybridization. The results
      will correlate the morphological characteristics of lesions with viral typing
      results. METHODS: This study examined prevalence of HPV 16 and 18 DNA in biopsies
      from 85 cervical cancer patients by ISPCR, employing HPV 16, 18 consensus
      primers. There are 45 patients with squamous cell carcinomas, 13 with
      adenocarcinoma, 2 with adenosquamous carcinomas, 3 with small cell carcinomas,
      and 22 carcinoma in situ. The relation between the types of HPV detected, tumor
      type, and clinical stage were analyzed. RESULTS: Fifty-two of 85 biopsies were
      HPV 16- or 18-positive, HPV 16 being the most prevalent type. Squamous cell
      carcinoma had a high prevalence of HPV 16 and adenocarcinoma had a high
      prevalence of HPV 18. HPV 18 was the predominant type among high clinical stage
      (III-IV) cases while HPV 16 and mixed HPV 16 with HPV18 were significantly
      correlated with low clinical stage (0-I-II). CONCLUSION: Our results indicate
      that certain malignant cervical tumor phenotypes and stages correlate with
      specific HPV type, and that ISPCR is a sensitive and fast method to detect HPV in
      these patients.

PMID- 11579388
TI  - Multidrug resistance gene (MDR-1) expression as a useful prognostic factor in
      patients with human hepatocellular carcinoma after surgical resection.
AB  - BACKGROUND: Multidrug resistance gene (MDR-1) overexpression has been correlated
      with tumor aggressiveness and worse prognosis in some human neoplasms. The aim of
      this study is to evaluate the clinical value of MDR-1 mRNA expression as a
      prognostic factor after surgical resection in human hepatocellular carcinoma
      (HCC). METHODS: MDR-1 mRNA levels in tissue samples from 34 patients with HCC,
      who underwent surgical resection, were measured by quantitative northern blot
      analysis. We stratified these patients into two groups according to a ratio of
      MDR-1 mRNA levels of HCC to nontumorous tissue; MDR-1 mRNA ratio > or = 1.0 and <
      1.0. The overall and disease-free survival rates were analyzed using multivariate
      regression analysis. RESULTS: The median survival periods were 10.3 and 35.8
      months for patients with the MDR-1 mRNA ratio > or = 1.0 and < 1.0, respectively,
      and the corresponding 5-year survival rates were 33 and 54%, respectively, P <
      0.05. The multivariate analysis revealed that TNM stage and MDR-1 mRNA ratio were
      independent factors for predicting overall survival after surgical resection.
      CONCLUSION: This study suggested that the measurement of the MDR-1 mRNA levels in
      HCC and nontumorous liver tissue might be a useful prognostic factor after
      surgical resection in patients with HCC.

PMID- 11579389
TI  - Bcl-X expression in esophageal squamous cell carcinoma: association with tumor
      progression and prognosis.
AB  - BACKGROUND AND OBJECTIVES: Bcl-2 family proteins are regulators of programmed
      cell death and important in the development and progression of human various
      tumors. The role of these proteins in the development, progression and
      differentiation of esophageal squamous cell carcinoma (ESCC) is unclear. METHODS:
      We investigated the expression of Bcl-2, Bcl-X, and Bax using
      immunohistochemistry in 86 ESCCs, and scored the expression by the weighted
      score. RESULTS: Bcl-2 expression related to pT category (P=0.043) and
      histological grade (P = 0.001). Bcl-X expression related to pT category (P =
      0.003), pN category (P = 0.041) and the number of positive nodes (P = 0.036), and
      had a tendency to relate to histological grade (P = 0.086). Bax expression had a
      tendency to relate to pN category (P = 0.081). The inverse relationship between
      Bcl-2 and Bcl-X expression was detected (P = 0.001), while the positive one
      between Bcl-X and Bax expression was detected (P = 0.014). Patients with low Bcl
      X weighted score had a significantly longer survival compared with those with
      high Bcl-X weighted score. Multivariate analysis revealed Bcl-X expression as the
      independent prognostic factors (P = 0.022). CONCLUSION: These results imply that
      Bcl-2 family proteins, especially Bcl-X, may contribute to the progression in
      ESCC.

PMID- 11579390
TI  - Interleukin-10 and interferon-gamma levels within the peritoneal cavity of
      patients with gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Immune status in the peritoneal cavity of patients
      with gastric cancer remains largely unknown. To clarify the clinical significance
      of the host immune response within the peritoneal cavity, we examined the levels
      of interferon-gamma (IFN-gamma), a type 1 cytokine, and interleukin-10 (IL-10), a
      type 2 cytokine, in peritoneal washings obtained from patients with gastric
      cancer. METHODS: Both the concentrations of IFN-gamma and of IL-10 in peritoneal
      washings obtained during surgery from 56 patients with gastric cancer were
      determined by an enzyme-linked immunosorbent assay. RESULTS: The IFN-gamma level
      was not correlated with the IL-10 level. The IL-10 level increased in a stage
      dependent manner. The high IL-10 level correlated with an unfavorable outcome,
      whereas there was no relationship between the IFN-gamma level and survival rate.
      However, among the stage III-IV cancer patients, the high IFN-gamma level
      correlated with a favorable outcome, while there was no relationship between the
      IL-10 level and survival rate. CONCLUSION: Although the IL-10 level increases
      with tumor progression, the outcome of patients with advanced gastric cancer may
      be affected by the IFN-gamma level, but not by the IL-10 level, in the peritoneal
      cavity.

PMID- 11579392
TI  - Prognostic significance of the expression of vascular endothelial growth factor
      (VEGF) and VEGF-C in gastric carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Angiogenic factors play a major role in tumor growth
      and metastasis. The purpose of this study was to clarify the prognostic
      significance of the expression of vascular endothelial growth factor (VEGF) and
      VEGF-C in gastric carcinoma. METHODS: Formalin-fixed and paraffin embedded
      sections of tumor tissue were obtained from 76 patients who underwent curative
      gastrectomy for gastric carcinoma. Immunohistochemical staining for VEGF and VEGF
      C was performed. RESULTS: VEGF and VEGF-C were positively expressed in 39 and 45%
      of the patients, respectively. No correlation existed between VEGF and VEGF-C
      expressions. VEGF expression was significantly correlated with venous invasion.
      VEGF-C expression was significantly correlated with lymphatic and venous
      invasion. Patients with positive staining for VEGF showed a significantly lower
      survival rate than VEGF negative patients. After subdivision, according to the
      combination of VEGF and VEGF-C expression, VEGF-C expression had a significant
      unfavorable impact on prognosis among patients with negative staining for VEGF.
      The expression of VEGF and/or VEGF-C was independent prognostic determinant by
      the multivariate survival analysis. CONCLUSIONS: The positive expression for VEGF
      and/or VEGF-C was an important prognostic determinant after curative gastrectomy
      for gastric carcinoma. VEGF-C may stimulate the tumor progression in the absence
      of VEGF.

PMID- 11579393
TI  - Chyle withdrawal from an implanted port in occult innominate vein stenosis.
AB  - Totally implantable venous devices are widely used for chemotherapy and
      parenteral nutrition. There have been many device-associated complications
      reported in the literature. Herein, we report a case of chyle withdrawal from an
      implanted port that occurred secondary to occult innominate vein stenosis in a
      patient receiving chemotherapy for rectal cancer with lung metastasis. The port
      remained patent and functioning well after balloon angioplasty.

PMID- 11579394
TI  - Two simple techniques to minimize venous bleeding during the Whipple procedure.

PMID- 11579396
TI  - New technique of reconstruction following hemimandibulectomy using titanium
      plate.

PMID- 11579397
TI  - Modified technique for esophagojejunostomy after total gastrectomy.

PMID- 11579398
TI  - Gray-scale and color Doppler sonographic findings in intratesticular varicocele.
AB  - PURPOSE: We studied the gray-scale and color Doppler sonographic findings in
      intratesticular varicoceles in 7 testes in 5 patients. METHODS: The study group
      comprised 5 infertile men referred for scrotal sonography and found to have
      intratesticular varicocele. Patients were examined at rest and during Valsalva's
      maneuver in supine and standing positions. A diagnosis of intratesticular
      varicocele was made when intratesticular veins visible on gray-scale sonography
      showed retrograde flow on color Doppler sonography either spontaneously or during
      Valsalva's maneuver. The maximum diameter of dilated intratesticular veins and
      the predominant site of venous dilatation (mediastinum testis versus subcapsular)
      were recorded. RESULTS: Seven testes in 5 patients harbored visibly enlarged
      intratesticular veins that showed retrograde flow either spontaneously or during
      Valsalva's maneuver. The condition was bilateral in 2 patients and left-sided in
      3 patients. The largest intratesticular vein measured less than 2.0 mm in
      diameter in 3 testes and was 2.0 mm or larger in 4 testes. In all affected
      testes, there was some degree of subcapsular venous dilatation, which in 3 testes
      was even more prominent than venous dilatation in the mediastinum testis. All
      intratesticular varicoceles were accompanied by extratesticular varicoceles.
      CONCLUSIONS: A threshold value of 2.0 mm seems inadequate for the diagnosis of
      intratesticular varicocele because obviously variceal venous structures with
      retrograde flow on color Doppler sonography may be smaller than 2.0 mm in
      diameter. Contrary to the previous descriptions of the entity, subcapsular veins
      may be affected to a greater degree than mediastinal veins in intratesticular
      varicocele.

PMID- 11579399
TI  - Relationship between sonographic and pathologic findings in epidermal inclusion
      cysts.
AB  - PURPOSE: We evaluated the sonographic findings in epidermal inclusion cysts and
      related them to the pathologic findings. METHODS: We retrospectively reviewed the
      sonograms and pathology specimens of 24 patients with pathologically proven
      epidermal inclusion cysts. We evaluated the lesions for shape, size, internal
      echogenicity, posterior sound enhancement, and presence of color Doppler signals.
      We classified the masses into 5 sonographic types according to their internal
      echogenicity. The relationship between the sonographic types and the pathologic
      findings was examined. RESULTS: The masses were ovoid or spherical in 17 cases
      (71%), lobulated in 5 (21%), and tubular in 2 (8%). The longest diameter ranged
      from 1 to 6 cm (mean, 3.1 cm). Twenty-three cases (96%) were associated with
      posterior sound enhancement. Color Doppler signals were absent in 20 cases, but
      some vascularity was noted in 4 ruptured epidermal cysts, in areas of granulation
      tissue. The most common sonographic type was a hypoechoic lesion with scattered
      echogenic reflectors (10 cases). Sonographic findings were related to the
      lamellation of keratin debris and the granulation tissue secondary to rupture.
      Most cases with a lobulated configuration (4 of 5) or color Doppler signals (4 of
      4) were ruptured cysts. CONCLUSIONS: Epidermal inclusion cysts most often
      appeared sonographically as a hypoechoic mass containing variable echogenic foci
      without color Doppler signals. Ruptured epidermal cysts, however, may have
      lobulated contours and show color Doppler signals, mimicking a solid mass.

PMID- 11579400
TI  - Power Doppler sonography of the kidney: effect of Valsalva's maneuver.
AB  - PURPOSE: It has been reported that an intra-abdominal pressure (IAP) above 15 mm
      Hg may cause oliguria and that an IAP above 25 mm Hg may cause anuria. Because
      Valsalva's maneuver yields an IAP exceeding 180 mm Hg, it is presumed to affect
      renal perfusion. We evaluated the ability of power Doppler sonography to depict
      the changes in renal blood flow during Valsalva's maneuver. METHODS: Seven
      healthy men aged 21-24 years and 1 50-year-old man with massive ascites
      participated in the study. With each healthy subject lying in a supine position,
      longitudinal power Doppler sonograms of the kidney were obtained and analyzed
      semiquantitatively during Valsalva's maneuver. Also, in the patient with massive
      ascites, power Doppler sonography was performed before and after paracentesis.
      RESULTS: Along with an increase in IAP, monitored as expiratory pressure during
      Valsalva's maneuver, power Doppler signals decreased as indicated by both visual
      impression and computer scores. In the patient with massive ascites, signal
      intensity increased after paracentesis. CONCLUSIONS: Our results demonstrated
      that an increase in IAP within the physiologic range affects renal perfusion and
      that power Doppler sonography depicts semiquantitatively the change in renal
      blood flow.

PMID- 11579401
TI  - Ultrasound-guided piezoelectric extracorporeal shock wave lithotripsy of parotid
      gland calculi.
AB  - PURPOSE: The introduction of piezoelectric extracorporeal shock wave lithotripsy
      (ESWL) has changed therapy for salivary calculi. This method seems especially
      suitable for treating calculi in the parotid gland. The purpose of this study was
      to evaluate ESWL in patients with such calculi. METHODS: From November 1990 to
      November 1999, all patients with sialolithiasis of the parotid gland were treated
      with piezoelectric ESWL. Three different lithotriptors were used over the 9-year
      study period. Results were analyzed according to both the patients' clinical
      status and follow-up sonograms. RESULTS: In total, 42 patients (21 women, 21 men;
      mean age, 59 years) were treated with ESWL. The mean follow-up period for all
      patients was 63 months (range, 7-96 months). After ESWL had been performed, 71%
      of the patients were completely free of symptoms, and 21% had marked improvement
      of their symptoms. Sixty-seven percent were completely free of calculi, and 27%
      had a marked reduction in the size of their calculi. Adverse effects of ESWL
      included temporary glandular swelling (4 patients), blood-tinged salivary
      secretions (9 patients), petechiae on the skin surface (3 patients), and parotid
      abscess (1 patient). CONCLUSIONS: ESWL is an outpatient procedure that can be
      performed without anesthesia and with scarcely any discomfort for patients.
      Conventional surgical procedures such as subtotal parotidectomy may be almost
      entirely replaced by ESWL because of the excellent treatment results and a very
      low rate of complications associated with ESWL. ESWL should be considered the
      treatment of choice for parotid calculi.

PMID- 11579402
TI  - Endoscopic sonography in the diagnosis of gallbladder wall lesions in patients
      with gallstones.
AB  - PURPOSE: The purpose of this study was to evaluate the diagnostic accuracy of
      endoscopic sonography (EUS) in the detection of gallbladder wall lesions in
      patients with and without gallstones. METHODS: We retrospectively reviewed the
      medical records, sonograms, and sonographic reports of 62 patients who underwent
      cholecystectomy for gallbladder wall lesions evaluated by EUS. We assessed the
      accuracy of EUS in diagnosing gallbladder wall lesions in the presence or absence
      of gallstones and on the basis of the size and number of stones and the size of
      the gallbladder wall lesions. We also evaluated the effect of acoustic shadowing.
      The EUS results were compared with the histopathologic results. RESULTS: EUS
      correctly diagnosed the gallbladder wall lesions in 17 (71%) of 24 patients with
      gallstones and in 34 (89%) of 38 patients without gallstones. The diagnostic
      accuracy of EUS was 86% in patients with gallbladder wall lesions smaller than 20
      mm and 79% in patients with gallbladder wall lesions 20 mm or larger. The
      diagnostic accuracy was 75% in patients with gallstones smaller than 5 mm and 67%
      in patients with stones 5 mm or larger. The accuracy was 67% in patients with 1-5
      stones and 83% in patients with 6 or more stones. None of these differences was
      statistically significant. Acoustic shadowing did not affect the diagnostic
      accuracy of EUS. CONCLUSIONS: The diagnostic accuracy of EUS for gallbladder wall
      lesions is not affected by the presence of gallstones. However, better diagnostic
      criteria must be established based on larger studies, and technical refinements
      of the equipment are needed to increase the accuracy of EUS in the diagnosis of
      gallbladder wall lesions.

PMID- 11579403
TI  - Endorectal sonographic appearances of rectal MALT lymphoma, its response to
      therapy, and local recurrence.
AB  - Endorectal sonography may significantly help to evaluate rectal lymphoma. We
      report the sonographic findings in a case of rectal non-Hodgkin's MALT (mucosa
      associated lymphoid tissue) lymphoma, including the monitoring of response to
      therapy and confirmation of recurrence, in a 45-year-old man. On endorectal
      sonography of the rectal wall, the mucosa was markedly thickened to 1.1 cm and
      was diffusely hypoechoic and risen into multiple polypoid folds. The submucosa
      and muscularis propria appeared normal. Multiple lymph nodes were visualized in
      the perirectal fat; they were homogeneously hypoechoic, were round or oval, and
      ranged from 1.0 cm to 2.6 cm. Endoscopic biopsies revealed a grade I non
      Hodgkin's MALT lymphoma. Following chemotherapy, endorectal sonography showed
      that the surface of the rectal mucosa had a smoother appearance and near-normal
      thickness, but lymph nodes, although smaller, remained visible in the perirectal
      fat. Four months later, endorectal sonography demonstrated a local relapse of
      disease, with significant thickening of the rectal mucosa and multiple lymph
      nodes visible in the perirectal fat. Following high-dose chemotherapy for the
      recurrence, endorectal sonography demonstrated a near-normal appearance of the
      rectal mucosa.

PMID- 11579404
TI  - Development of intrahepatic arterial shunts in a transplanted liver: a potential
      pitfall for Doppler sonography.
AB  - We describe the hemodynamic features and anatomic basis of false-negative Doppler
      sonographic findings compared with angiographic findings in a 42-year-old woman
      after orthotopic liver transplantation complicated by hepatic artery thrombosis.
      Complete common hepatic artery thrombosis was demonstrated by Doppler sonography
      and digital subtraction angiography (DSA) on the first postoperative day. A
      thrombectomy was performed. DSA on the third day after transplantation again
      showed occlusion of the left hepatic artery. No perfusion was observed in the
      left hepatic lobe. Liver function remained normal. Doppler sonography on days 8,
      10, and 16 after transplantation demonstrated arterial blood flow in both the
      right and left lobes of the liver, suggesting patent left and right hepatic
      arteries. Repeat DSA revealed that the arterial flow in the left lobe depended on
      large, intrahepatic shunts originating from the right hepatic artery. Apparently,
      shunts can develop within a few days in a transplanted liver from radiologically
      undetectable structures into vessel-like channels capable of supplying the entire
      left hepatic lobe.

PMID- 11579405
TI  - Sonographic diagnosis of pancreatic islet cell tumor: value of intermittent
      harmonic imaging.
AB  - We describe a case of nonfunctioning islet cell tumor of the pancreas diagnosed
      preoperatively by intermittent harmonic power Doppler imaging and digital
      subtraction gray-scale harmonic imaging and the use of the contrast agent SH U
      508A (Levovist). Hypervascularity and tumor perfusion were clearly demonstrated
      with both harmonic imaging techniques in the early arterial phase. Sonographic
      findings were confirmed by other modalities and by histopathologic examination.

PMID- 11579406
TI  - Fungal brain abscesses in neonates: Sonographic appearances and corresponding
      histopathologic findings.
AB  - Extremely preterm neonates and neonates with predisposing conditions such as
      congenital or acquired immunodeficiency are at high risk for systemic fungal
      infection. Abscess formation in the brain is a severe complication that occurs in
      70% of neonates with systemic fungal infection. Cerebral sonography can be used
      to diagnose abscesses in the brain in these patients. We report 2 sonographic
      presentations of fungal brain abscesses in neonates confirmed by postmortem
      histopathologic examination. The first patient, an extremely preterm neonate of
      23 weeks' gestation with a systemic Candida albicans infection, had multiple
      small, round, hypoechoic lesions with echogenic rims in both brain hemispheres.
      The second patient, a term neonate with disseminated aspergillosis and DiGeorge
      syndrome, had a few large echogenic areas in the right periventricular region.
      Brain imaging should be considered in the diagnostic workup in neonates with
      suspected systemic fungal infection. Cerebral involvement can be diagnosed at the
      bedside with cerebral sonography.

PMID- 11579407
TI  - Prenatal sonographic diagnosis of Klippel-Trenaunay-Weber syndrome with cardiac
      failure.
AB  - This report describes the prenatal sonographic diagnosis of a case of Klippel
      Trenaunay-Weber syndrome. The sonographic appearance of this disorder was
      characterized by the presence of multiple distorted cystic areas involving the
      right leg and abdomen and cardiomegaly with early fetal heart failure. Despite
      the prenatal detection of the extensive cutaneous and visceral involvement, the
      infant died soon after birth of high-output cardiac failure and Kasabach-Merritt
      syndrome.

PMID- 11579419
TI  - Mitochondrial diseases: beyond the magic circle.

PMID- 11579420
TI  - Clinical spectrum and diagnosis of mitochondrial disorders.
AB  - Respiratory chain deficiencies have long been regarded as neuromuscular diseases
      mostly originating from mutations in the mitochondrial DNA. Actually, oxidative
      phosphorylation, i.e., adenosine triphosphate (ATP) synthesis-coupled electron
      transfer from substrate to oxygen through the respiratory chain, does not only
      occur in the neuromuscular system. For this reason, a respiratory chain
      deficiency can theoretically give rise to any symptom, in any organ or tissue, at
      any age and with any mode of inheritance, owing to the dual genetic origin of
      respiratory chain enzymes (nuclear DNA and mitochondrial DNA). In recent years,
      it has become increasingly clear that genetic defects of oxidative
      phosphorylation account for a large variety of clinical symptoms in both
      childhood and adulthood. Diagnosis of a respiratory chain deficiency is difficult
      initially when only one symptom is present, and easier when additional, seemingly
      unrelated, symptoms are observed. The clinical heterogeneity is echoed by the
      genetic heterogeneity illustrated by the increasing number of nuclear genes that
      have been shown to be involved in these diseases. In the absence of clear-cut
      genotype-phenotype correlations and in front of the large number of possibly
      involved genes, biochemical analyses are still the cornerstone of the diagnosis
      of this condition.

PMID- 11579421
TI  - Mitochondrial DNA mutations in human disease.
AB  - The small, maternally inherited mitochondrial DNA (mtDNA) has turned out to be a
      Pandora's box of pathogenic mutations: 13 years into the era of "molecular
      mitochondrial medicine," more than 100 pathogenic point mutations and innumerable
      rearrangements have been associated with a striking variety of multisystemic as
      well as tissue-specific human diseases. After reviewing the principles of
      mitochondrial genetics, we consider disorders due to mutations in genes affecting
      mitochondrial protein synthesis and disorders due to mutations in protein-coding
      genes. In contrast to the remarkable progress in our understanding of etiology,
      pathogenesis is only partially explained by the rules of mitochondrial genetics
      and remains largely unclear. We review recent progress in prenatal diagnosis,
      epidemiology, and in the development of animal models harboring mtDNA mutations.

PMID- 11579422
TI  - Mitochondria and degenerative disorders.
AB  - In mammalian cells, mitochondria provide energy from aerobic metabolism. They
      play an important regulatory role in apoptosis, produce and detoxify free
      radicals, and serve as a cellular calcium buffer. Neurodegenerative disorders
      involving mitochondria can be divided into those caused by oxidative
      phosphorylation (OXPHOS) abnormalities either due to mitochondrial DNA (mtDNA)
      abnormalities, e.g., chronic external ophthalmoplegia, or due to nuclear
      mutations of OXPHOS proteins, e.g., complex I and II associated with Leigh
      syndrome. There are diseases caused by nuclear genes encoding non-OXPHOS
      mitochondrial proteins, such as frataxin in Friedreich ataxia (which is likely to
      play an important role in mitochondrial-cytosolic iron cycling), paraplegin
      (possibly a mitochondrial ATP-dependent zinc metalloprotease of the AAA-ATPases
      in hereditary spastic paraparesis), and possibly Wilson disease protein (an
      abnormal copper transporting ATP-dependent P-type ATPase associated with Wilson
      disease). Huntingon disease is an example of diseases with OXPHOS defects
      associated with mutations of nuclear genes encoding non-mitochondrial proteins
      such as huntingtin. There are also disorders with evidence of mitochondrial
      involvement that cannot as yet be assigned. These include Parkinson disease
      (where a complex I defect is described and free radicals are generated from
      dopamine metabolism), amyotrophic lateral sclerosis, and Alzheimer disease, where
      there is evidence to suggest mitochondrial involvement perhaps secondary to other
      abnormalities.

PMID- 11579423
TI  - Respiratory chain complex I deficiency.
AB  - Oxidative phosphorylation disorders make a contribution of 1 per 10,000 live
      births in man, of which isolated complex I deficiency is frequently the cause.
      Complex I, or NADH:ubiquinone oxidoreductase, is the largest multi-protein enzyme
      complex of the mitochondrial electron transfer chain. In complex I deficiency,
      various clinical phenotypes have been recognized, often resulting in multi-system
      disorders with a fatal outcome at a young age. Recent advances in complex I
      deficiency, regarding clinical, biochemical, and molecular aspects are described.
      However, the genetic causes of about 60% of complex I deficiency remain unclear.
      As a consequence, further research will be needed to clarify the genetic defects
      in the remaining cases. Novel strategies in which interesting non-structural
      nuclear-encoded disease-causing genes may be found, as well as the molecular
      genetic composition of human complex I, are presented.

PMID- 11579424
TI  - Cytochrome c oxidase deficiency.
AB  - Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial
      respiratory chain, catalyzing the transfer of electrons from reduced cytochrome c
      to molecular oxygen. It is composed of 13 structural subunits, three of which are
      encoded in mtDNA and form the catalytic core of the enzyme. In addition to these
      structural subunits, a large number of accessory factors are necessary for the
      assembly and maintenance of the active holoenzyme complex. Most isolated COX
      deficiencies are inherited as autosomal recessive disorders; mutations in the
      mtDNA-encoded COX subunit genes are relatively rare. These mutations are
      associated with a wide spectrum of clinical phenotypes ranging from isolated
      myopathy to multisystem disease, with onset from late childhood to adulthood.
      Autosomal recessive COX deficiencies generally have a very early age of onset and
      a fatal outcome. Several clinical presentations have been described including
      Leigh Syndrome, hypertrophic cardiomyopathy and myopathy, and fatal infantile
      lactic acidosis. Surprisingly, mutations in the nuclear-encoded structural COX
      subunits have not been found in association with any of these phenotypes.
      Mutations have, however, been identified in several COX assembly factors: SURF1
      (Leigh Syndrome), SCO2 (hypertrophic cardiomyopathy), SCO1 (hepatic failure,
      ketoacidotic coma), and COX10 (encephalopathy, tubulopathy). As all of these
      assembly factors are ubiquitously expressed, the molecular basis for the
      different clinical presentations remains unexplained. Although the genetic
      defects in the majority of patients with COX deficiency are unknown, it is likely
      that most will be solved in the near future using functional complementation
      techniques.

PMID- 11579425
TI  - Diseases caused by nuclear genes affecting mtDNA stability.
AB  - Diseases caused by nuclear genes that affect mitochondrial DNA (mtDNA) stability
      are an interesting group of mitochondrial disorders, involving both cellular
      genomes. In these disorders, a primary nuclear gene defect causes secondary mtDNA
      loss or deletion formation, which leads to tissue dysfunction. Therefore, the
      diseases clinically resemble those caused by mtDNA mutations, but follow a
      Mendelian inheritance pattern. Several clinical entities associated with multiple
      mtDNA deletions have been characterized, the most frequently described being
      autosomal dominant progressive external ophthalmoplegia (adPEO). MtDNA depletion
      syndrome (MDS) is a severe disease of childhood, in which tissue-specific loss of
      mtDNA is seen. Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)
      patients may have multiple mtDNA deletions and/or mtDNA depletion. Recent reports
      of thymidine phosphorylase mutations in MNGIE and adenine nucleotide translocator
      mutations in adPEO have given new insights into the mechanisms of mtDNA
      maintenance in mammals. The common mechanism underlying both of these gene
      defects could be disturbed mitochondrial nucleoside pools, the building blocks of
      mtDNA. Future studies on MNGIE and adPEO pathogenesis, and identification of
      additional gene defects in adPEO and MDS will provide further understanding about
      the mammalian mtDNA maintenance and the crosstalk between the nuclear and
      mitochondrial genomes.

PMID- 11579426
TI  - Mitochondria, oxygen free radicals, and apoptosis.
AB  - Reactive oxygen species (ROS) generated by mitochondria are produced as by
      products of normal oxidative metabolism. The fate of these species is governed by
      a number of factors that vary from tissue to tissue in mammals and may be
      involved in the pathogenesis of disease. Reactive oxygen species are also invoked
      as agents that are important in the processes which become active in cells
      undergoing apoptosis. Integration of knowledge surrounding these different
      aspects of ROS generation is difficult and reveals considerable gaps in our
      understanding.

PMID- 11579427
TI  - Mouse models for mitochondrial disease.
AB  - Mutations in mitochondrial genes encoded by both mitochondrial DNA (mtDNA) and
      nuclear DNA (nDNA) genes have been implicated in a wide range of neuromuscular
      diseases. MtDNA base substitution and rearrangement mutations generally
      inactivate one or more tRNA or rRNA genes and can cause myopathy, cardiomyopathy,
      cataracts, growth retardation, diabetes, etc. nDNA mutations can cause Leigh
      syndrome, cardiomyopathy, and nephropathy, due to defects in oxidative
      phosphorylation (OXPHOS) enzyme complexes; cartilage-hair hypoplasia (CHH) and
      mtDNA depletion syndrome, through defects in mitochondrial nucleic acid
      metabolism; and ophthalmoplegia with multiple mtDNA deletions, caused by adenine
      nucleotide translocator-1 (ANT1) mutations. Mouse models have been prepared that
      recapitulate a number of these diseases. The mtDNA 16S rRNA chloramphenicol (CAP)
      resistance mutation was introduced into the mouse female germline and caused
      cataracts and rod and cone abnormalities in chimeras and neonatal lethal myopathy
      and cardiomyopathy in mutant animals. A mtDNA deletion was introduced into the
      mouse germline and caused myopathy, cardiomyopathy, and nephropathy. Conditional
      inactivation of the nDNA mitochondrial transcription factor (Tfam) gene in the
      heart resulted in neonatal lethal cardiomyopathy, while its inactivation in the
      pancreatic beta-cells caused diabetes. The ATP/ADP ratio was implicated in
      mitochondrial diabetes through transgenic modification of the beta-cell ATP
      sensitive K(+) channel (K(ATP)). Mutational inactivation of the mouse Ant1 gene
      resulted in myopathy, cardiomyopathy, and multiple mtDNA deletions in association
      with elevated reactive oxygen species (ROS) production. Inactivation of uncoupler
      proteins (Ucp) 1-3 revealed that mitochondrial Delta Psi regulated ROS
      production. The role of mitochondrial ROS toxicity in disease and aging was
      confirmed by inactivating glutathione peroxidase (GPx1), resulting in growth
      retardation, and by total and partial inactivation of Mn superoxide dismutase
      (MnSOD; Sod2), resulting in neonatal lethal dilated cardiomyopathy and
      accelerated apoptosis in aging, respectively. The importance of mitochondrial ROS
      in degenerative diseases and aging was confirmed by treating Sod2 -/- mice and C.
      elegans with catalytic antioxidant drugs.

PMID- 11579428
TI  - Epidemiology and treatment of mitochondrial disorders.
AB  - The last ten years have seen a huge increase in the number of different genetic
      defects found in patients with mitochondrial disorders, but the true impact of
      mitochondrial disease is only just becoming apparent. Mitochondrial diseases are
      far more common than was anticipated. Although there have also been major
      advances in our understanding of mitochondrial pathology, the clinical management
      of patients with mitochondrial disease is largely supportive. In this article, we
      focus on primary disorders of the mitochondrial respiratory chain and mtDNA
      defects. We review the available epidemiological data, outline current strategies
      for the management of mitochondrial disease, and highlight new therapeutic
      approaches that may prove useful in the future.

PMID- 11579429
TI  - Mitochondrial disorders: genetics, counseling, prenatal diagnosis and
      reproductive options.
AB  - Most patients with mitochondrial disorders are diagnosed by finding a respiratory
      chain enzyme defect or a mutation in the mitochondrial DNA (mtDNA). The provision
      of accurate genetic counseling and reproductive options to these families is
      complicated by the unique genetic features of mtDNA that distinguish it from
      Mendelian genetics. These include maternal inheritance, heteroplasmy, the
      threshold effect, the mitochondrial bottleneck, tissue variation, and selection.
      Although we still have much to learn about mtDNA genetics, it is now possible to
      provide useful guidance to families with an mtDNA mutation or a respiratory chain
      enzyme defect. We describe a range of current reproductive options that may be
      considered for prevention of transmission of mtDNA mutations, including the use
      of donor oocytes, prenatal diagnosis (by chorionic villus sampling or
      amniocentesis), and preimplantation genetic diagnosis, plus possible future
      options such as nuclear transfer and cytoplasmic transfer. For common mtDNA
      mutations associated with mitochondrial cytopathies (such as NARP, Leigh Disease,
      MELAS, MERRF, Leber's Hereditary Optic Neuropathy, CPEO, Kearns-Sayre syndrome,
      and Pearson syndrome), we summarize the available data on recurrence risk and
      discuss the relative advantages and disadvantages of reproductive options.

PMID- 11579430
TI  - The genetics of epilepsy.

PMID- 11579431
TI  - Chromosome imbalances associated with epilepsy.
AB  - Epilepsy is among the most frequent findings in many, especially autosomal,
      chromosome aberrations. Its incidence, however, is very variable, and there are
      very few aberrations in which epilepsy is a constant finding. Even siblings and
      monozygotic twins with the same aberration are often discordant for seizure
      disorders. Similar observations can be made for congenital (major) malformations
      in chromosome aberrations. The common explanation is that in these instances
      epilepsy is not caused by the action of a single gene in single or triple dose,
      but is influenced by the combined action of a number of genes within and outside
      of the aneuploid segment. The situation is comparable to a polygenic model of
      inheritance. Gene mutations associated with epilepsy are known, to date, only for
      two disorders: the lissencephaly 1 gene in Miller-Dieker syndrome and mutations
      in the UBE3A gene in Angelman syndrome. Chromosome aberrations in which epilepsy
      is a major and consistent finding include Angelman syndrome due to loss of the
      maternal 15q11.2-q12 segment, tetrasomy of the maternal segment 15pter-q13 due to
      an additional inv dup chromosome, Miller-Dieker syndrome due to deletion of the
      17p13.3 segment including the lissencephaly1 gene, ring chromosome 20, and Wolf
      Hirschhorn syndrome due to deletion of at least the 4p16.3 segment.

PMID- 11579432
TI  - Rearrangements of chromosome 15 in epilepsy.
AB  - A number of observations point to chromosome 15 as a good candidate to harbor
      genes involved in epilepsy. This hypothesis is supported by at least two lines of
      evidence: one is the finding that haploinsufficiency of the 15q11-q13 region, of
      maternal origin, is responsible for Angelman syndrome, one of the cardinal
      manifestations of which is epilepsy; the second is the observation that extra
      copies of this same genomic region, in the form of inv-dup(15) or
      intrachromosomal duplications, again of maternal origin, are usually associated
      with a severe neurological phenotype characterized by developmental delay and
      untreatable seizures. Therefore, both reduced and increased dosage of genes from
      the 15q11-q13 region, possibly subjected to maternal imprinting, appear to be
      causally involved in severe forms of epilepsy. We tested the hypothesis that
      submicroscopic rearrangements of this genomic region might be responsible for
      nonsyndromic epilepsy in both familial and sporadic forms. To this purpose, we
      genotyped 118 epileptic patients and their parents with closely spaced
      microsatellite markers mapped within the 15q11-q13 region. We report on the
      results of these studies and review the relevant literature.

PMID- 11579433
TI  - Advances in the genetics of progressive myoclonus epilepsy.
AB  - The genetic progressive myoclonus epilepsies (PMEs) are clinically characterized
      by the triad of stimulus sensitive myoclonus (segmental lightning like muscular
      jerks), epilepsy (grand mal and absences) and progressive neurologic
      deterioration (dementia, ataxia, and various neurologic signs depending on the
      cause). Etiologically heterogenous, PMEs are rare and mostly autosomal recessive
      disorders, with the exception of autosomal dominant dentatorubral-pallidoluysian
      atrophy and mitochondrial encephalomyopathy with ragged red fibers (MERRF). In
      the last five years, specific mutations have been defined in Lafora disease (gene
      for laforin or dual specificity phosphatase in 6q24), Unverricht-Lundborg disease
      (cystatin B in 21q22.3), Jansky-Bielschowsky ceroid lipofuscinoses (CLN2 gene for
      tripeptidyl peptidase 1 in 11q15), Finnish variant of late infantile ceroid
      lipofuscinoses (CLN5 gene in 13q21-32 encodes 407 amino acids with two
      transmembrane helices of unknown function), juvenile ceroid lipofuscinoses or
      Batten disease (CLN3 gene in 16p encodes 438 amino acid protein of unknown
      function), a subtype of Batten disease and infantile ceroid lipofuscinoses of the
      Haltia-Santavuori type (both are caused by mutations in palmitoyl-protein
      thiosterase gene at 1p32), dentadorubropallidoluysian atrophy (CAG repeats in a
      gene in 12p13.31) and the mitochondrial syndrome MERRF (tRNA Lys mutation in
      mitochondrial DNA). In this review, we cover mainly these rapid advances.

PMID- 11579434
TI  - Genes and mutations in idiopathic epilepsy.
AB  - Partial or generalized idiopathic epilepsies, which account for up to 40% of all
      epilepsies, are characterized by a mostly benign course and no apparent etiology
      other than a genetic predisposition. So far, the genetic defects underlying three
      different idiopathic epilepsy syndromes have been identified: mutations in the
      CHRNA4- or CHRNB subunits of the neuronal nicotinic acetylcholine receptor are
      found in familial nocturnal frontal lobe epilepsy, while defects in the voltage
      gated potassium channels KCNQ2 and KCNQ3 have recently been identified in benign
      familial neonatal convulsions. The syndrome of "generalized epilepsy with febrile
      seizures plus" can be caused by mutations affecting the voltage-gated sodium
      channel subunits SCN1B and SCN1A or the gamma 2-subunit of the GABA(A) receptor.
      The results of recent molecular studies contributed largely to our understanding
      of the etiology and pathophysiology of idiopathic epilepsies.

PMID- 11579435
TI  - Ion channels and epilepsy.
AB  - Ion channels provide the basis for the regulation of excitability in the central
      nervous system and in other excitable tissues such as skeletal and heart muscle.
      Consequently, mutations in ion channel encoding genes are found in a variety of
      inherited diseases associated with hyper- or hypoexcitability of the affected
      tissue, the so-called 'channelopathies.' An increasing number of epileptic
      syndromes belongs to this group of rare disorders: Autosomal dominant nocturnal
      frontal lobe epilepsy is caused by mutations in a neuronal nicotinic
      acetylcholine receptor (affected genes: CHRNA4, CHRNB2), benign familial neonatal
      convulsions by mutations in potassium channels constituting the M-current (KCNQ2,
      KCNQ3), generalized epilepsy with febrile seizures plus by mutations in subunits
      of the voltage-gated sodium channel or the GABA(A) receptor (SCN1B, SCN1A,
      GABRG2), and episodic ataxia type 1-which is associated with epilepsy in a few
      patients--by mutations within another voltage-gated potassium channel (KCNA1).
      These rare disorders provide interesting models to study the etiology and
      pathophysiology of disturbed excitability in molecular detail. On the basis of
      genetic and electrophysiologic studies of the channelopathies, novel therapeutic
      strategies can be developed, as has been shown recently for the antiepileptic
      drug retigabine activating neuronal KCNQ potassium channels.

PMID- 11579436
TI  - Epilepsy and genetic malformations of the cerebral cortex.
AB  - Malformations of the cerebral cortex are an important cause of developmental
      disabilities and epilepsy. Here we review those malformations for which a genetic
      basis has been elucidated or is suspected and the types of associated epilepsy.
      Schizencephaly (cleft brain) has a wide anatomo-clinical spectrum, including
      partial epilepsy in most patients. Familial occurrence is rare. Heterozygous
      mutations in the EMX2 gene were reported in 13 patients. X-linked bilateral
      periventricular nodular heterotopia (BPNH) consists of typical BPNH with epilepsy
      in females and prenatal lethality in males. About 88% of patients have partial
      epilepsy. Filamin A mutations, all leading to a truncated protein, have been
      reported in three families and in sporadic patients. The most frequent forms of
      lissencephaly (agyria-pachygyria) are caused by mutations of LIS1. XLIS mutations
      cause classical lissencephaly in hemizygous males and subcortical band
      heterotopia (SBH) in heterozygous females. The thickness of the heterotopic band
      and the degree of pachygyria correlate with the likelihood of developing Lennox
      Gastaut syndrome. Mutations of the coding region of XLIS were found in all
      reported pedigrees and in 38-91% of sporadic female patients with SBH. With few
      exceptions, children with LIS1 mutations have isolated lissencephaly, with severe
      developmental delay and infantile spasms. Autosomal recessive lissencephaly with
      cerebellar hypoplasia, accompanied by severe developmental delay, seizures, and
      hypotonia has been associated with mutations of the reelin gene. Fukuyama
      congenital muscular dystrophy is due to mutations of the fukutin gene and is
      accompanied by polymicrogyria. Febrile seizures and epilepsy with generalized
      tonic-convulsions appear in about 50% of children but are usually not severe.
      Tuberous sclerosis (TS) is caused by mutations in at least two genes, TSC1 and
      TSC2; 75% of cases are sporadic; 60% of patients have epilepsy, manifested in 50%
      of them as infantile spasms. TSC1 mutations seem to cause a milder disease with
      fewer cortical tubers and lower frequency of seizures. Among several syndromes
      featuring polymicrogyria, bilateral perisylvian polymicrogyria had familial
      occurrence on several occasions. Genetic heterogeneity is likely, including
      autosomal recessive, X-linked dominant, X-linked recessive inheritance, and
      association with 22q11.2 deletions. About 65% of patients have severe epilepsy,
      often Lennox-Gastaut syndrome.

PMID- 11579438
TI  - Vancomycin, teicoplanin, and ramoplanin: synthetic and mechanistic studies.
AB  - Vancomycin, teicoplanin, and ramoplanin are potent glycopeptide antibiotics that
      act by inhibiting bacterial cell wall biosynthesis. The former are used
      clinically as the antibiotics of last resort for the treatment of methicillin
      resistant Staphylococcus aureus and the latter is a promising new antibiotic that
      is not susceptible to the emerging bacterial resistance to vancomycin and
      teicoplanin. A summary of our recent total synthesis of the vancomycin aglycon,
      our first and second generation total syntheses of the teicoplanin aglycon, and
      our progress on the total synthesis of the ramoplanins is presented. This work
      lays the foundation for ongoing structure-function studies on the antibiotics
      that may clarify or define their site and mechanism of action leading to the
      development of improved or reengineered antibiotics.

PMID- 11579439
TI  - Pharmacokinetics and its role in small molecule drug discovery research.
AB  - Pharmacokinetics (PK), which describes the disposition of a drug in the body,
      should be a primary consideration in the selection of a drug candidate,
      ultimately contributing to its eventual clinical success or failure. Accordingly,
      a sound understanding of PK concepts and an appreciation of the judicious use of
      PK and related (e.g., metabolism, transporter) data in drug discovery can be
      beneficial to those involved in the process. This review defines important PK
      parameters (e.g., clearance, volume of distribution, half-life), describes
      methods of PK data analysis (noncompartmental vs. compartmental) and provides an
      overview of additional concepts such as allometric scaling, PK/pharmacodynamic
      modeling, and nonlinear PK. Furthermore, the role and strategic use of PK screens
      in drug discovery are discussed.

PMID- 11579440
TI  - Role of drug metabolism in drug discovery and development.
AB  - Metabolism by the host organism is one of the most important determinants of the
      pharmacokinetic profile of a drug. High metabolic lability usually leads to poor
      bioavailability and high clearance. Formation of active or toxic metabolites will
      have an impact on the pharmacological and toxicological outcomes. There is also
      potential for drug-drug interactions with coadministered drugs due to inhibition
      and/or induction of drug metabolism pathways. Hence, optimization of the
      metabolic liability and drug-drug interaction potential of the new chemical
      entities are some of the most important steps during the drug discovery process.
      The rate and site(s) of metabolism of new chemical entities by drug metabolizing
      enzymes are amenable to modulation by appropriate structural changes. Similarly,
      the potential for drug-drug interactions can also be minimized by appropriate
      structural modifications to the drug candidate. However, the optimization of the
      metabolic stability and drug-drug interaction potential during drug discovery
      stage has been largely by empirical methods and by trial and error. Recently, a
      lot of effort has been applied to develop predictive methods to aid the
      optimization process during drug discovery and development. This article reviews
      the role of drug metabolism in drug discovery and development.

PMID- 11579441
TI  - Optimization of metabolic stability as a goal of modern drug design.
AB  - Metabolism and other pharmacokinetic (PK) studies have always played a critical
      role in helping to optimize the bioavailability and duration of action of new
      drugs thereby increasing their success rate. With the advent of automated
      combinatorial synthesis, high-throughput pharmacological testing, and the ability
      to create extensive databases in the past decade, drug discovery has undergone an
      amazing evolution. With the increased throughput of drug discovery, metabolism
      and other PK studies have evolved to keep pace. Often called "early ADME"
      studies, these studies are characterized by parallel processing and higher
      throughput than before. This article focuses on a particular class of early ADME
      (absorption, distribution mechanism, and excretion) studies known as "metabolic
      stability" studies. The theoretical basis for metabolic stability and its
      relationship to the concept of metabolic intrinsic clearance is briefly
      presented. Some key relationships between structure and metabolism are
      summarized. Several case studies from recent medicinal chemistry literature are
      reviewed to exemplify how metabolic stability studies influenced drug design and
      led to improvements in bioavailability and half-life. Finally, future trends in
      drug metabolism and analytical chemistry and how they may influence metabolic
      stability studies are reviewed.

PMID- 11579442
TI  - Peptide hormone binding to G-protein-coupled receptors: structural
      characterization via NMR techniques.
AB  - G-protein-coupled receptors (GPCRs) allow cells to respond to calcium, hormones,
      and neurotransmitters. Not surprisingly, they currently make up the largest
      family of validated drug targets. Rational drug design for molecular regulators
      targeting GPCRs has been limited to theoretical-based computational approaches. X
      ray crystallography of intact GPCRs has provided the topological orientation of
      the seven transmembrane helices, but limited structural information of the
      extracellular and intracellular loops and protein termini. In this review we
      detail an NMR-based approach which provides the high-resolution structural
      features on the extracellular domains of GPCRs and the ligand/receptor complexes
      formed upon titration of the peptide hormone. The results provide important
      contact points and a high-resolution description of the ligand/receptor
      interactions, which may be useful for the rational design of therapeutic agents
      targeting GPCRs. Recent results from our investigation of the cholecystokinin
      peptide hormone system are used to highlight this approach.

PMID- 11579443
TI  - Modeling the 3D structure of GPCRs from sequence.
AB  - G-protein-coupled receptors (GPCRs) are a large and functionally diverse protein
      superfamily, which form a seven transmembrane (TM) helices bundle with
      alternating extra-cellular and intracellular loops. GPCRs are considered to be
      one of the most important groups of drug targets because they are involved in a
      broad range of body functions and processes and are related to major diseases. In
      this paper we present a new technology, named PREDICT, for modeling the 3D
      structure of any GPCR from its amino acid sequence. This approach takes into
      account both internal protein properties (i.e., the amino acid sequence) and the
      properties of the membrane environment. Unlike competing approaches, the new
      technology does not rely on the single known structure of rhodopsin, and is thus
      capable of predicting novel GPCR conformations. We demonstrate the capabilities
      of PREDICT in reproducing the known experimental structure of rhodopsin. In
      principle, PREDICT-generated models offer new opportunities for structure-based
      drug discovery towards GPCR targets.

PMID- 11579444
TI  - Resolution, configurational assignment, and enantiopharmacology at glutamate
      receptors of 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) and
      demethyl-ACPA.
AB  - We have previously described (RS)-2-amino-3-(3-carboxy-5-methyl-4
      isoxazolyl)propionic acid (ACPA) as a potent agonist at the (RS)-2-amino-3-(3
      hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor subtype of (S)
      glutamic acid (Glu) receptors. We now report the chromatographic resolution of
      ACPA and (RS)-2-amino-3-(3-carboxy-4-isoxazolyl)propionic acid (demethyl-ACPA)
      using a Sumichiral OA-5000 column. The configuration of the enantiomers of both
      compounds have been assigned based on X-ray crystallographic analyses, supported
      by circular dichroism spectra and elution orders on chiral HPLC columns.
      Furthermore, the enantiopharmacology of ACPA and demethyl-ACPA was investigated
      using radioligand binding and cortical wedge electrophysiological assay systems
      and cloned metabotropic Glu receptors. (S)-ACPA showed high affinity in AMPA
      binding (IC(50) = 0.025 microM), low affinity in kainic acid binding (IC(50) =
      3.6 microM), and potent AMPA receptor agonist activity on cortical neurons
      (EC(50) = 0.25 microM), whereas (R)-ACPA was essentially inactive. Like (S)-ACPA,
      (S)-demethyl-ACPA displayed high AMPA receptor affinity (IC(50) = 0.039 microM),
      but was found to be a relatively weak AMPA receptor agonist (EC(50) = 12 microM).
      The stereoselectivity observed for demethyl-ACPA was high when based on AMPA
      receptor affinity (eudismic ratio = 250), but low when based on
      electrophysiological activity (eudismic ratio = 10). (R)-Demethyl-ACPA also
      possessed a weak NMDA receptor antagonist activity (IC(50) = 220 microM). Among
      the enantiomers tested, only (S)-demethyl-ACPA showed activity at metabotropic
      receptors, being a weak antagonist at the mGlu(2) receptor subtype (K(B) = 148
      microM).

PMID- 11579445
TI  - Six-membered cyclic sulfites derived from glucofuranose and 1,2,4-butanetriol.
AB  - Six-membered cyclic sulfites derived from glucofuranose derivatives 5, 6 and from
      1-O-tert-butyldimethylsilil-1,2,4-butanetriol 12 were synthesized and separated
      into pure diastereomers which were in turn subjected to the sequence of reactions
      leading to the introduction of the terminal vinyl ether fragment. Reactivity and
      applicability of cyclic sulfites as intermediates in [2+2]cycloaddition of
      chlorosulfonyl isocyanate (CSI) to vinyl ethers were studied. The cycloaddition
      to vinyl ethers 19 and 20 proceeded in low yield and low asymmetric induction, in
      the case of the former, and moderate yield and pronounced asymmetric induction,
      in the case of the latter. The (1)H-NMR spectra of sulfites 13-16 reveal a
      preference of the sulfite oxygen atom for the axial position. Thus, well-defined
      conformation in solution for compounds 13 and 15 and a mixture of the two
      possible chair forms for sulfites 14 and 16 could be assigned. The stretching
      frequency of the S-->O bond in stable conformation with an axial sulfite oxygen
      occurs in the range 1,160-1,210 cm(-1), whereas conformationally mobile sulfites
      exhibit corresponding absorption above 1,220 cm(-1). The absolute configuration
      assignments of sulfites 7, 8, 15, 16 and 25-28 were done empirically based on the
      combined analysis of the NMR, IR, X-ray, and dichroic data. It was demonstrated
      that the sign of the Cotton effect around 194 nm correlated with the absolute
      stereochemistry at the sulfur atom in a sulfite chromophore.

PMID- 11579446
TI  - Tetranuclear titanium 7,7'-modified binaphtholate cluster as a novel chiral Lewis
      acid catalyst.
AB  - Chiral tetranuclear Ti cluster, a cubic structure constituted of four Ti atoms
      and OHs, and six (R)-binaphthols (BINOL) bridged two Ti atoms as ligands, is
      shown to be a novel chiral Lewis acid catalyst for the [2+3] cycloaddition
      reaction with nitrones. The chiral Ti clusters with 7,7'-substituted (R)-BINOL
      ligands was synthesized to give enhanced enantiomeric excesses up to 78% ee.

PMID- 11579447
TI  - Identification of the configuration of neosartorin by long-range nuclear
      Overhauser effect measurements.
AB  - The relative configuration of the two xanthene units of neosartorin, a new
      ergochrome biosynthesised by the soil mould Neosartorya fischeri, was determined
      using a 1D double-pulsed field gradient spin-echo NOESY experiment. It was found
      that both units have the same relative stereochemistry. Long-range nonbonding
      interactions between the substituents of different xanthene units stabilise the
      nonplanar configuration of the two aromatic rings A and A' connecting both
      monomer units of neosartorin.

PMID- 11579448
TI  - Conformational investigation of two isomeric chiral porphyrins: a convergent
      approach with different techniques.
AB  - The conformation in solution of two atropisomeric meso-tetrabinaphthyl
      porphyrins, used as catalytic precursors in asymmetric synthesis, was studied by
      means of experimental ((1)H-NMR ROESY, UV-Vis, and circular dichroism) and
      computational (semiempirical structure optimization, DeVoe's coupled oscillators
      calculations) methods. UV-Vis and CD spectra are calculated for several molecular
      models, with a systematic sampling of the conformational space, and compared to
      the experimental ones, leading to a structural hypothesis which is confirmed by
      NMR and PM3.

PMID- 11579449
TI  - Optimization of the chiral separation of some 2-arylpropionic acids on an avidin
      column by modeling a combined response.
AB  - The enantiomeric separation of some nonsteroidal antiinflammatory drugs was
      investigated on an avidin column. An experimental design approach (central
      composite design) was used to evaluate the effects of three method parameters
      (pH, concentration of organic modifier, and buffer concentration) on the analysis
      time and the resolution, as well as to model these responses. This revealed that
      the organic modifier concentration and sometimes the pH are significant
      parameters to control because of their influence on both analysis time and
      resolution. Furthermore, the central composite design results were combined in a
      multicriteria decision-making approach in order to obtain a set of optimal
      experimental conditions leading to the most desirable compromise between
      resolution and analysis time.

PMID- 11579450
TI  - Optical resolution of 6-fluoro-2-methyl-1,2,3,4-tetrahydroquinoline by
      supercritical fluid extraction.
AB  - 6-Fluoro-2-methyl-1,2,3,4-tetrahydroquinoline (FTHQ) enantiomers were separated
      by supercritical fluid extraction using carbon dioxide. Diastereoisomeric salts
      were formed from the racemic base with less than one equivalent of O,O'-di-(4
      toluoyl)-(2R,3R)-tartaric acid (DPTTA). Further purification was achieved by
      partial salt formation of the enantiomeric mixture with an achiral acid (HCl)
      followed by the supercritical fluid extraction of the free enantiomers.

PMID- 11579451
TI  - Ab initio (CASPT2) excited state calculations, including circular dichroism, of
      helically twisted cyanine dyes.
AB  - Ab initio calculations at the CASSCF/CASPT2 level were performed on helically
      twisted mono-, tri-, and pentamethine cyanine dyes in the all-Z-configurations.
      Excitation energies and oscillator and rotatory strengths were calculated for the
      five lowest energy singlet states. Both the long wavelength methine band and the
      cis-band could be identified unambiguously from their configurational parentage.
      The calculated state energies are within 0.09 eV of the experimental value for
      the methine band and within 0.16 eV for the cis-band. The calculated rotatory
      strengths of the methine band shows sign inversion as the length of the
      chromophore increases: negative for the short monomethine, strongly positive for
      the pentamethine. The trimethine presents a borderline case: the measured
      rotatory strength is almost nil, the calculated one depends on the geometry.
      There is good agreement between rotatory strengths calculated in the velocity and
      in the length formalism.

PMID- 11579452
TI  - Application of L-threonine aldolase-catalyzed reaction to the preparation of
      protected 3R,5R-dihydroxy-L-homoproline as a mimetic of idulonic acid.
AB  - A facile synthesis of 3R,5R-dihydroxy-L-homoproline as idulonic acid mimic, of
      which the carboxyl and 3-hydroxyl groups were protected, was attained using L
      threonine aldolase-catalyzed reaction. Idulonic acid is a key acidic sugar of the
      b-FGF binding domain in heparin and heparan sulfate. Moreover, the synthetic
      precursor of N-acetyl-4-deoxy-D-mannosamine, which is a potent inhibitor of NeuAc
      synthase, was prepared from the side product of the enzymatic aldol condensation.

PMID- 11579453
TI  - Mechanism of chiral recognition in the enantioseparation of 2-aryloxypropionic
      acids on new brush-type chiral stationary phases.
AB  - New brush-type chiral stationary phases (CSP I-IV) comprising N-3,5,6-trichloro
      2,4-dicyanophenyl-L-alpha-amino acids (1-4) were prepared by binding of chiral
      selectors 1-4 to gamma-aminopropyl silica gel. To check the role of excess free
      aminopropyl groups, CSP V was prepared by binding N-3,5,6-trichloro-2,4
      dicyanophenyl-L-alanyl-(3-triethoxysilyl)propylamide to unmodified silica gel.
      The best separation of racemic 2-aryloxypropionic acids (TR-1-13) was obtained
      with CSP I; the -(-)-S enantiomer were regularly eluted first, as determined by a
      CD detector. The mechanism of chiral recognition implies a synergistic
      interaction of carboxylic acid analyte with the chiral selector and achiral free
      gamma-aminopropyl units on silica. In fact, CSP V, which is lacking an achiral
      aminopropyl spacer, shows a lower separation ability for 2-aryloxypropionic
      acids, but a similar enantioselective discrimination of esters TR-19-20, in
      comparison with CSP I. CSP I-IV retain unaltered separation ability after a few
      months of continuous work using a large number of various mobile phases.

PMID- 11579454
TI  - Chirality recognition in solvent-free solid-state crystallization: chiral adduct
      formation by bis-beta-naphthol derivatives and benzoquinone crystals.
AB  - New adduct crystals were obtained by simply mixing/grinding component crystals of
      bis-beta-naphthol (BN) derivatives with benzoquinone (BQ) under solvent-free
      conditions. Chiral recognition was found to operate during this process and
      either a racemic or a chiral crystal of a BN derivative produced an adduct
      crystal with BQ by solid-state crystallization. The chirality preference changed
      subtly according to the molecular structure of the BN derivative. Even in
      circumstances in which no adduct was formed, addition of a third component, such
      as crystals of naphthalene, to the grinding mixture yielded an adduct crystal.
      Remarkably, these adduct crystals were found to decompose spontaneously with time
      and revert to the starting crystal of the BN derivative by losing BQ molecules
      from the crystal lattice. Local melting of crystals by the grinding pressure was
      found unlikely to be the mechanism of adduct formation. Overall, these results
      demonstrate that molecules in the solid state could change their relative
      location and hydrogen bonding partners, thereby exerting chiral discrimination.

PMID- 11579455
TI  - Enantiomeric recognition of chiral 3,3-bridged-1,1'-binaphthol dimer toward alpha
      phenylethylamine and alpha-amino acid ester.
AB  - The 1,1'-binaphthol-based dimers with p-phenylenebis(2-ethynyl) spacer, (+)-6 and
      (+)-2, were synthesized as chiral host compounds. (1)H NMR, UV-vis, and
      fluorescent titration were used to evaluate the enantiomeric recognition
      abilities of the chiral host dimers toward the guest amine 7 and alpha-amino acid
      ester 8. The chiral BINOL-based dimers were found to have good enantiomeric
      recognition ability. The computer simulation of the host-guest complex molecules
      was carried out to describe the conformational changes of both naphthyl ring in
      the molecule of chiral host dimer after complexation with the guest molecule.

PMID- 11579456
TI  - Absolute configuration at C14 and C85 in prymnesin-2, a potent hemolytic and
      ichthyotoxic glycoside isolated from the red tide alga Prymnesium parvum.
AB  - Prymnesin-2 is a potent red tide toxin characterized by a highly oxidized C(90)
      carbon chain and multiple functional groups. Succeeding the assignment of the
      relative stereochemistry in the polycyclic-ether segment, the absolute
      configurations of two chiral centers in linear chain parts were elucidated. The
      configuration at C14 bearing an amino group was determined to be S by using a
      chiral anisotropic reagent and that at chlorinated C85 to be S by fluorimetric
      chiral HPLC comparison between a degradation product and synthetic references.

PMID- 11579457
TI  - Enantiomers of 2-[(Acylamino)ethyl]-1,4-benzodiazepines, potent ligands of kappa
      opioid receptor: chiral chromatographic resolution, configurational assignment
      and biological activity.
AB  - Compounds 2a and 3a-e are racemic 2-[(acylamino)ethyl]-1,4-benzodiazepines,
      tifluadom analogs, with high affinity and selectivity towards the kappa-opioid
      receptor. We describe the enantiomeric separation of all compounds through liquid
      chromatography with chiral stationary phases, as well as the resolution of the
      enantiomers of the most interesting compounds, 2a and 3a, by the semipreparative
      column Chiralpak AD. The configuration of the resolved enantiomers was
      investigated: the comparative study of CD and (1)H NMR spectra shows that
      compounds (-)-2a and (-)-3a have the same absolute configuration of (+)-(S)
      tifluadom. A study on the stereoselective interaction with opiate receptors is
      reported.

PMID- 11579459
TI  - Sporadic multiple primary melanoma cases: CDKN2A germline mutations with a
      founder effect.
AB  - Multiple primary cancers are one of the hallmarks of inherited predisposition.
      Outside the familial context, multiple primary tumors could be related either to
      germline de novo mutations or to low-penetrance mutations, in predisposing genes.
      We selected 100 patients who displayed multiple primary melanoma (MPM) without
      any known melanoma cases recorded within their families and looked for germline
      mutations in the two melanoma-predisposing genes identified to date, CDKN2A and
      CDK4 exon 2. Nine patients (9%) had germline mutations in CDKN2A, whereas none
      carried germline mutations in exon 2 of CDK4. Seven cases displayed a recurrent
      missense mutation, G101W, already described in more than 20 melanoma-prone
      families; one case carried a missense mutation never reported to date (P114S),
      and the last case was a carrier of a 6 bp insertion at nucleotide 57 resulting in
      a duplication of codons 18 and 19. To ascertain whether the G101W was a
      mutational hot spot for de novo mutations or a common founder mutation, we
      genotyped eight microsatellite markers flanking the CDKN2A gene. After allowing
      for recombination over time, haplotype sharing provided evidence for an original
      G101W mutation common to 6 out of 7 sporadic MPM cases. Therefore, it can be
      concluded that de novo germline CDKN2A mutations associated with MPM are rare.

PMID- 11579460
TI  - Genome-wide analysis of sixteen chordomas by comparative genomic hybridization
      and cytogenetics of the first human chordoma cell line, U-CH1.
AB  - Cytogenetic information on chordomas is rudimentary and restricted to GTG-banding
      analysis of 26 cases worldwide. In this study, we present the chromosomal
      imbalances detected in a series of 16 chordomas (10 sacrococcyeal, five
      sphenooccipital, and one spinal) from 13 patients using comparative genomic
      hybridization (CGH) and fluorescence in situ hybridization (FISH). On average,
      3.2 losses and 4.2 gains were detected per tumor. The most common DNA copy number
      alterations were losses on chromosomal arms 3p (50%) and 1p (44%). Losses of 3p
      were detected in five of seven primary chordomas. Therefore, the loss of 3p might
      be an early event in chordoma genesis. The most common gains involved 7q (69%),
      20 (50%), 5q (38%), and 12q (38%). Additionally, we raised the first human
      chordoma cell line, U-CH1, from a recurrence of a sacral chordoma. U-CH1 and its
      parent tumor had almost the same CGH profile. According to GTG-banding and
      multicolor FISH, U-CH1 has the following clonal chromosomal abnormalities:
      der(1)t(1;22), del(4), +del(5), +del(6), +7, del(9), del(10), +der(20)t(10;20),
      +21. Thus, the novel permanent human chordoma cell line U-CH1 has chordoma
      typical cytogenetic aberrations. Our data suggest that tumor suppressor genes or
      mismatch repair genes (located at 1p31 and 3p14) and oncogenes (located in 7q36)
      might be involved in chordoma genesis.

PMID- 11579461
TI  - GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24).
AB  - We report a novel MLL-associated chromosome translocation t(11;14)(q23;q24) in a
      child who showed signs of acute undifferentiated leukemia 3 years after intensive
      chemotherapy that included the topoisomerase-II inhibitor VP 16. Screening of a
      cDNA library of the patient's leukemic cells showed a novel fusion transcript
      between MLL and the Gephyrin (GPHN) gene on 14q24. The resulting MLL-GPHN fusion
      gene encodes MLL AT hook motifs and a DNA methyltransferase homology domain fused
      to the C-terminal half of Gephyrin, including a presumed tubulin binding site and
      a domain homologous to the Escherichia coli molybdenum cofactor biosynthesis
      protein MoeA. Genomic breakpoint analysis showed potential in vitro topoisomerase
      II DNA-binding sites spanning the breakpoints in both MLL and GPHN but no
      flanking sequences that might mediate homologous recombination. This suggests
      that MLL-GPHN may have been generated by VP 16/topoisomerase-II-induced DNA
      double-strand breaks, followed by error-prone DNA repair via non-homologous end
      joining. Gephyrin was originally identified as a submembraneous scaffold protein
      that anchors and immobilizes postsynaptic membrane neurotransmitter receptors to
      underlying cytoskeletal elements. It also is reported to bind to
      phosphatidylinositol 3,4,5-triphosphate binding proteins involved in actin
      dynamics and downstream signaling and interacts with ATM-related family member
      RAFT1. Gephyrin domains in the chimeric protein therefore could contribute novel
      signal sequences or might modify MLL activity by oligomerization or intracellular
      redistribution.

PMID- 11579462
TI  - DNA polymerase eta undergoes alternative splicing, protects against UV
      sensitivity and apoptosis, and suppresses Mre11-dependent recombination.
AB  - Polymerase eta (pol eta) is a low-fidelity DNA polymerase that is the product of
      the gene, POLH, associated with the human XP variant disorder in which there is
      an extremely high level of solar-induced skin carcinogenesis. The complete human
      genomic sequence spans about 40 kb containing 10 coding exons and a cDNA of 2.14
      kb; exon I is untranslated and is 6 kb upstream from the first coding exon. Using
      bacterial artificial chromosomes (BACs), the gene was mapped to human chromosome
      band 6p21 and mouse band 17D. The gene is expressed in most tissues, except for
      very low or undetectable levels in peripheral lymphocytes, fetal spleen, and
      adult muscle; exon II, however, is frequently spliced out in normal cells and in
      almost half the transcripts in the testis and fetal liver. Expression of POLH in
      a multicopy episomal vector proved nonviable, suggesting that overexpression is
      toxic. Expression from chromosomally integrated linear copies using either an EF1
      alpha or CMV promoter was functional, resulting in cell lines with low or high
      levels of pol eta protein, respectively. Point mutations in the center of the
      gene and in a C-terminal cysteine and deletion of exon II resulted in
      inactivation, but addition of a terminal 3 amino acid C-terminal tag, or an N- or
      C-terminal green fluorescent protein, had no effect on function. A low level of
      expression of pol eta eliminated hMre11 recombination and partially restored UV
      survival, but did not prevent UV-induced apoptosis, which required higher levels
      of expression. Polymerase eta is therefore involved in S-phase checkpoint and
      signal transduction pathways that lead to arrest in S, apoptosis, and
      recombination. In normal cells, the predominant mechanism of replication of UV
      damage involves pol eta-dependent bypass, and Mre11-dependent recombination that
      acts is a secondary, backup mechanism when cells are severely depleted of pol
      eta.

PMID- 11579463
TI  - Localisation of a novel region of recurrent amplification in follicular lymphoma
      to an approximately 6.8 Mb region of 13q32-33.
AB  - Follicular lymphoma (FL) is characterised by the presence of the
      t(14;18)(q32;q21) and represents approximately 25% of new cases of non-Hodgkin's
      lymphoma. While the t(14;18) is a well-documented rearrangement, the role of
      secondary cytogenetic abnormalities in the development and progression of these
      tumours remains unclear. Comparative genomic hybridisation was used to
      characterise changes in DNA copy number in tumour DNA from patients with this
      malignancy. The mean numbers of deletion and amplification events found in each
      of the 45 samples studied were 1.8 and 2.3, respectively. Regions of recurrent
      (>10% tumour samples) gain involved chromosomes 2p13-16 (16%), 7 (20%), 12 (16%),
      13q21-33 (18%), 18 (27%), and X (36%) and frequent losses localised to 6q (29%)
      and 17p (20%). Amplification of chromosome 13 represents a novel finding in FL.
      The minimal amplified region was refined to a 6.8-Mb interval of 13q32-33 between
      the BAC clones 88K16 and 44H20 by fluorescence in situ hybridisation studies
      using metaphase chromosomes derived from tumour material. There are a number of
      reports in the literature suggesting that amplification of chromosome 13 also
      occurs in other human cancers. The location of the putative oncogene on 13q
      described here in follicular and transformed lymphoma may also be important in
      the evolution of many other malignancies.

PMID- 11579464
TI  - Chromosome 21 abnormalities with AML1 amplification in acute lymphoblastic
      leukemia.
AB  - Fluorescence in situ hybridization (FISH) studies were performed in three cases
      of acute lymphoblastic leukemia (ALL) with marker chromosomes to analyze the
      contribution of chromosome 21 in these markers. FISH with a chromosome 21
      painting probe confirmed that chromosome 21 was involved in all three cases. FISH
      with YAC probes showed that the number of extra copies varied according to their
      location on chromosome 21. Attention was focused on the AML1 gene, which was
      present as five copies in most of the cells exhibiting the marker chromosomes. As
      controls, 11 cases of childhood ALL were studied with PAC probes covering AML1.
      The results agreed with the banded karyotypes in 10 patients. FISH uncovered a
      clone with four copies of AML1 which were only observed by FISH analysis of
      interphase nuclei in one patient. No point mutation was detected in exons 3-5,
      encoding the runt domain of AML1, in the three cases, suggesting an oncogenic
      role of wild-type AML1 amplification.

PMID- 11579465
TI  - Novel evidence of a role for chromosome 1 pericentric heterochromatin in the
      pathogenesis of B-cell lymphoma and multiple myeloma.
AB  - 1q rearrangement is a remarkably frequent secondary chromosomal change in both
      non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM), where it is associated
      with tumor progression. To gain insight into 1q rearrangement-associated disease
      mechanisms, we used fluorescence in situ hybridization (FISH) to search for
      recurring 1q breaks in 35 lymphoma samples (31 NHL patients and 4 lymphoma
      derived cell lines) as well as 22 MM patients with cytogenetically determined 1q
      abnormalities. Strikingly, dual-color FISH analysis with chromosome 1 centromere
      and 1q12-specific probes identified constitutive heterochromatin band 1q12 as the
      single most frequent breakpoint site in both NHL and MM (39% and 89% of 1q
      breaks, respectively). These rearrangements consistently generated aberrant
      heterochromatin/euchromatin junctions and gain of 1q12 material. A further 30% of
      NHL 1q breaks specifically involved two other novel, closely spaced sites
      (clusters I and II) within a 2.5 Mb region of proximal 1q21 (D1S3620 to D1S3623).
      A possible association between these sites and NHL subtype was evident; the
      cluster I rearrangement was frequent in follicular and diffuse large cell
      lymphoma, whereas the cluster II rearrangement was more frequently observed in
      diffuse small-cell lymphoma (2/2 marginal zone lymphomas, 1/2 atypical chronic
      lymphocytic leukemias, and 1 lymphoplasmacytic lymphoma in this series).
      Candidate oncogenes bordering this interval (BCL9 and AF1Q) were not rearranged
      in any patient except one (AF1Q). This study provides the first evidence of
      involvement of 1q12 constitutive heterochromatin in the pathogenesis of NHL and
      MM and indicates proximal 1q21 to be of specific pathological significance in
      NHL.

PMID- 11579466
TI  - Detection of illegitimate rearrangement within the immunoglobulin locus on
      14q32.3 in B-cell malignancies using end-sequenced probes.
AB  - Translocation involving the immunoglobulin heavy chain (IGH) locus is a recurring
      event in B-cell oncogenesis. The aim of this study was to characterize clones
      from bacterial artificial chromosome (BAC) libraries and/or bacteriophage P1
      artificial chromosome libraries spanning the IGH locus for detection of
      illegitimate rearrangement within the region by fluorescence in situ
      hybridization (FISH). In silico analysis of the IGH variable (IGHV) DNA sequence
      (NT_001716.v1) was performed to identify BAC probes located within the IGHV
      cluster. Clones of the constant (IGHC) cluster were found in the literature or at
      http://www.biologia.uniba.it/rmc/. Validation, orientation, and overlap of these
      probes were confirmed using interphase-, metaphase-, and fiber-FISH. We have
      identified seven BAC end-sequenced probes (3087C18, 47P23, 76N15, 12F16, 101G24,
      112H5, and 151B17) covering 612 kb of the distal IGHV cluster, which, together
      with probes covering the IGHC cluster (11771 and 998D24), could be used in
      interphase nuclei and metaphase chromosome analysis. A visual split of the IGHV
      and IGHC clusters indicating a translocation was analyzed by dual-color FISH in a
      series of 21 cell lines of different origins. Translocations were found, as
      expected, in eight of eight myelomas, four of four lymphomas, none of five
      leukemias, and none of four Epstein-Barr virus-transformed B-lymphoblastoid cell
      lines. To summarize, we have established a set of IGHV and IGHC probes that can
      be used for universal screening of illegitimate rearrangement within the IGH
      locus in B-cell malignancies. These probes allow for routine FISH analysis to
      detect this early central oncogenic event.

PMID- 11579467
TI  - Novel alternative PBX3 isoforms in leukemia cells with distinct interaction
      specificities.
AB  - PBX3 is a member of the PBX family of TALE homeobox genes. The prototypic member,
      PBX1, was first identified in chromosomal translocations in B-lineage leukemia
      and is required for normal hematopoiesis. PBX2 and PBX3 were later identified as
      members of this highly conserved family by their strong homology to PBX1. While
      the expression pattern of PBX1 is restricted, PBX2 and PBX3 are ubiquitously
      expressed. Little is known about the functional role of PBX3. Our studies
      identified two PBX3 transcripts alternative to the canonical forms, PBX3A and
      PBX3B, resulting from a novel splice in PBX3. These new isoforms, named PBX3C and
      PBX3D, have been detected in all tissues and cell lines tested. Intriguingly,
      expression of PBX3D is favored in normal cells, whereas PBX3C expression is
      favored in leukemia cells. Functional studies showed that PBX3C and PBX3D
      proteins were unable to interact with the PBX-interacting factor PREP1 and weakly
      interacted with MEIS proteins. We propose that PBX3C and PBX3D may affect PBX3
      mediated transcriptional regulation by acting in opposition to the known PBX
      proteins through alternative PBX3 complex formation. The identification and
      characterization of these novel PBX3 isoforms provide a foundation for a better
      understanding of the biological role of PBX3.

PMID- 11579468
TI  - Splicing factor SRP20 is a novel partner of BCL6 in a t(3;6)(q27;p21)
      translocation in transformed follicular lymphoma.
AB  - The BCL6 gene mapped at chromosome band 3q27 encodes a zinc-finger transcription
      factor and is frequently rearranged and deregulated in B-cell non-Hodgkin's
      lymphoma (NHL) by promiscuous chromosomal translocations which involve diverse
      genes. We identified a novel t(3;6)(q27;p21) in a follicular lymphoma (FL) with
      histologic evidence of transformation and, by cloning the translocation junction,
      determined that the SRP20 gene was the partner. In this translocation, the 5'
      regulatory region of the BCL6 was substituted by a putative regulatory region of
      SRP20. Previously, we hypothesized that substitution of BCL6 promoter by those of
      the partner genes that were constitutively expressed throughout B-cell
      development led to persistent and inappropriate expression of BCL6. We examined
      the expression pattern of SRP20 during B-cell development by Northern blot
      analysis of a panel of B-cell lines representing various stages of B-cell
      development and noted that SRP20 mRNA was expressed throughout B-cell
      development. The SRP20 gene plays an important role in regulation of pre-mRNA
      splicing, and is expressed specifically in lymphoid tissues. This study provides
      the first evidence of SRP20 gene rearrangement in human hematopoietic
      malignancies.

PMID- 11579469
TI  - Frequent gain of chromosome 19 in megakaryoblastic leukemias detected by
      comparative genomic hybridization.
AB  - Acute megakaryocytic leukemia is a rare subtype of AML that is often difficult to
      diagnose; it is most commonly associated with Down syndrome in children. To
      identify chromosomal imbalances and rearrangements associated with acute
      megakaryocytic leukemia, we used G-banding, comparative genomic hybridization
      (CGH), and whole chromosome painting (WCP) on a variety of primary patients'
      samples and leukemia cell lines. The most common abnormality was gain of
      chromosome 19 or arm 19q, which was detected by CGH in four of 12 (33.3%) primary
      samples and nine of 11 (81.8%) cell lines. In none of the primary samples was
      this abnormality detected by G-banding analysis. WCP was used to define further
      the nature of the chromosome 19 gain in the cell lines, which was found to be due
      to the presence of additional 19q material on marker chromosomes or to cryptic
      translocations involving 19q. The most common chromosomal loss--detected only in
      the cell lines--was deletion of chromosomal band 13q14, which was seen in six of
      11 (54.5%) cell lines. Other recurrent changes included gains of 1p, 6p, 8q, 11q,
      15q, 17q, and 21q and losses of 2, 4q, 5q, 7q, 9p, and 11p. Combining
      conventional and molecular cytogenetic analyses defined recurrent clonal
      chromosomal abnormalities, which will aid in the identification of critical genes
      that are abnormal in acute megakaryocytic leukemia cells.

PMID- 11579471
TI  - [Reconstruction of the cervical esophagus].

PMID- 11579470
TI  - [Social withdrawal in the adolescent and young adult].
AB  - The phenomenon of social withdrawal in adolescence and young adulthood has become
      one of the major issues in community mental health care. The objective of this
      paper is to provide an overview on the psychopathological understanding of this
      condition and the mental health care measures required. Social withdrawal is a
      condition arising from the backdrop of various psychopathological backgrounds
      including schizophrenia, mood disorder, anxiety disorder, personality disorder,
      and some cases with a background of developmental disorder. The importance of
      establishing policies for treatment and support based upon appropriate assessment
      of each individual case, the schizoid pathology found in common among many cases,
      and the issues in psychoanalytic psychotherapy for these schizoid cases are
      reviewed. Furthermore, the need for systematizing approaches enabling
      consultations sought by family members, and a guideline and problems pertaining
      to crisis intervention for cases exhibiting severe violence or antisocial
      behavior are presented as issues to be addressed in future mental health care.

PMID- 11579472
TI  - [Microvascular anastomoses in cervical esophageal reconstruction].
AB  - Ischemia or hemostasis in the gastric, jejunal, and colonic pedicle after
      esophagectomy is believed to contribute significantly to postoperative
      complications. With the advent of microvascular anastomoses, many surgeons have
      adopted vascular augmentation (supercharge) as a means of avoiding these
      difficulties. Microsurgical free tissue transfer represented by the free jejunum
      and forearm flap also plays an important role in esophageal reconstruction. In
      this paper, the authors introduce the technical points important for successful
      revascularization including the choice of recipient vessels, setting up of the
      reconstructive materials, and postoperative monitoring. In cases of gastric pull
      up elevated via posterior mediastinum, the left gastroduodenal vessels are
      anastomosed to the cervical transverse or superior thyroidal vessels. In cases of
      duodenal or colonic pull-up elevated via the anterosternal route, the vascular
      pedicles are anastomosed to the internal mammary vessels which are dissected by
      resecting the costal cartilage. When the free jejunum flap is used, the cervical
      transverse or superior thyroidal vessels are most frequently used as recipients.
      Postoperative monitoring of free flaps is performed using Doppler ultrasound or
      through a small skin incision made above the transferred tissue. Although gastric
      or colonic pull-up is difficult to monitor, color Doppler sonography permits
      quantitative analysis of blood flow and may be a useful option.

PMID- 11579473
TI  - [Surgical treatment of carcinoma of the hypopharynx and cervical esophagus].
AB  - This paper discusses several recent advances in surgical methods for treatment of
      cancer of the hypopharynx and cervical esophagus. The standard surgical technique
      for the primary lesion is laryngo-pharyngo-esophagectomy in which the larynx is
      usually resected to prevent postoperative aspiration even if the cancer does not
      directly involve the larynx. Another common technique is total laryngectomy plus
      partial resection of the hypopharynx, where a very limited lesion in the
      unilateral pyriform sinus is resected with the surrounding hypopharyngeal mucosa
      and larynx. In this case, the defect in the hypopharyngeal mucosa is primarily
      sutured or reconstructed with a graft based on its size. Experience has
      demonstrated that the larynx can be preserved without any postoperative
      aspiration if it is not involved by cancer and surgeons design the lines of
      resection and the postoperative shape of the reconstructed area to prevent
      aspiration. It has also been demonstrated that even if a part of the larynx is
      involved and must be resected, the remaining portion of the larynx can sometimes
      be preserved without any distinct aspiration. There are two common surgical
      techniques for neck lymph nodes. Radical neck dissection is the classic one, in
      which the lymphatic tissues together with the surrounding structures, including
      the sternocleidomastoid muscle, internal jugular vein, and accessory nerve are
      resected. Conservative neck dissection resects the lymphatic tissues only and
      preserves other structures. Currently, the standard surgical technique is
      conservative neck dissection. Radical neck dissection is rarely performed now
      because its morbidity is much higher and its superiority in treatment results has
      not been established.

PMID- 11579474
TI  - [A new technique to preserve the larynx in surgery for cervical esophageal
      carcinoma and the limit of its practical application].
AB  - A new technique to preserve the larynx in esophagectomy for cervical esophageal
      carcinoma is described. The trachea, which prevents exposure of the cervical
      esophagus, is dissected while maintaining the continuity of the recurrent
      laryngeal nerve. The tracheal stumps were turned over like a double door, and the
      esophageal tumor is excised with sufficient margins for suturing. The cervical
      esophagus is safely replaced with a free jejunum or the stomach followed by
      tracheal reconnection. The technique of tracheal reconnection in the neck is not
      difficult and is a safe procedure. Anastomotic insufficiency of the trachea may
      be compensated for with a temporary tracheostomy. This method is applicable in
      esophagectomy not only with curative but also with palliative intent to offer the
      patient a better quality of life. Theoretically, this method can be applied even
      for tumors minimally invading the trachea in which the invaded tracheal segment
      can be excised in combination with the esophagus, followed by tracheal
      anastomosis. Because this technique is a safe and easy procedure, it is
      recommended in cases in which proximal anastomosis appears difficult.

PMID- 11579475
TI  - [Reconstruction after cervical esophagectomy using a free jejunal graft].
AB  - Reconstruction after cervical esophagectomy using a free jejunal graft and
      forming an additional "vocal canal" are described. It is necessary to pay
      attention to several points, for example, selection of the jejunal graft,
      selection of the cervical vessels for anastomosis, technique of hypopharyngeal
      jejunal anastomosis, and postoperative management of the anastomotic vessels.
      These contribute to the improvement of patient quality of life. Forming an
      additional "vocal canal" in patients who underwent radical surgery is
      particularly desirable. In this article, we introduce our operative method.

PMID- 11579476
TI  - [Reconstruction of the cervical esophagus by interposition of the transverse
      colon].
AB  - Currently, the first choice viscus for reconstruction after total
      pharyngolaryngoesophagectomy is a jejunal interposition. This requires at least
      one end-to-side anastomosis in the pharyngo-jejunal anastomosis, esophago-jejunal
      anastomosis, or both due to the small diameter of the jejunum and round shape of
      the mesenterium. Furthermore, the jejunal graft experiences a spasm when the
      patient swallows. For such reasons the jejunal free graft is not suitable for
      swallowing. On the other hand, the transverse colon graft is more appropriate for
      reconstruction for the following reasons: it has a straight shape; end-to-end
      anastomosis is possible to both the pharynx and esophagus; and there are
      postoperative complications due to simple anastomosis of the remaining colon
      after graft removal. Blood vessel anastomoses, performed using microsurgery
      techniques, are followed by esophageal reconstructive anastomoses. Fifteen
      patients successfully underwent this type of reconstruction in our institution.

PMID- 11579477
TI  - [Reconstruction of the cervical esophagus using cutaneous or musculocutaneous
      flaps].
AB  - Reconstruction of the cervical esophagus using cutaneous or musculocutaneous
      flaps is described. The delto-pectoral cutaneous flap, latissimus dorsi or
      pectoris major musculocutaneous flap, free forearm cutaneous flap, and free
      rectus abdominis musculocutaneous flap are generally used for reconstruction of
      the cervical esophagus. Although free jejunal transfer with microsurgery is now
      common for reconstruction of the cervical esophagus, cutaneous or
      musculocutaneous flaps remain useful in high-risk patients or patients in whom
      free jejunal transfer or gastrointestinal reconstruction would prove incompetency
      due to a history of abdominal surgery or other reasons. Cutaneous or
      musculocutaneous flaps are also used in patients with failure of free jejunal
      transfer or incurable fistula after reconstruction using the stomach or colon for
      thoracic esophageal cancer.

PMID- 11579478
TI  - [Surgical voice restoration after pharyngolaryngoesophagectomy].
AB  - Although pharyngolaryngoesophagectomy (PLE) offers the only reliable possibility
      for cure in patients with advanced carcinomas of the cervical esophagus, the
      majority must reconcile themselves to subsequent voicelessness. Various surgical
      methods for voice restoration have been devised to solve this problem. Among
      these methods, the most common following PLE are the tracheogastric shunt, double
      tracheo-esophagogastric shunt, elephant trunk-shaped tracheo-esophageal shunt,
      tracheo-jejunal shunt, and tracheo-ileocecal shunt. The basic premise of these
      procedures is to introduce expiratory air from the trachea into the reconstructed
      esophagus to produce voice without aspiration of liquid or food during
      deglutition. The resultant speech is acceptable in most patients.

PMID- 11579481
TI  - [The validity of repeated mail surveys concerning smoking habits for Japanese
      physicians].
AB  - PURPOSE: A cross-sectional study of smoking prevalence among medical doctors was
      performed using questionnaires. Mailing four times proved essential in order to
      obtain a reasonable number of responses from the subjects. The objective of the
      present study was to analyze the smoking characteristics of the subjects who
      returned the questionnaires after the second to fourth mailings. METHODS: A set
      of an anonymous questionnaire and a letter from the President of the Japan
      Medical Association (JMA) requesting cooperation was mailed with a return
      envelope with the subject's name and address written to 3,000 male and 1,500
      female doctors randomly selected from the roster membership of the JMA. The
      survey was conducted between February and June 2000. RESULTS: The collection rate
      after the first mailing was 66%, while the subtotal collection rate for the
      second through fourth mailings was 21%, bringing the grand-total to 87%. The
      total prevalence of smoking among the subjects who had sent back the
      questionnaire on the second to fourth mailings was approximately 1.5 times higher
      than for those who had sent back the questionnaire after the initial mailing for
      both male and female subjects. As to other characteristics of the subjects who
      only responded after the second to fourth mailings were: working in hospitals
      (odds ratios; male: 1.39, female: 1.47), not giving smoking cessation guidance
      (odds ratio; male: 0.58), and not recognizing the idea that doctors should not
      smoke (odds ratio; female: 0.67). CONCLUSIONS: The results suggested that for
      future surveys on smoking to be conducted in academic institutions or work
      places, efforts to obtain responses from those who do not answer the first
      attempt should take into consideration these points.

PMID- 11579482
TI  - [The validity of revised death certificates (ICD-10) for ischemic heart disease
      in Oita City, Japan].
AB  - PURPOSE: Mortality statistics have recorded an increased number of deaths from
      ischemic heart disease (IHD) since death certificates were revised to reflect the
      International Classification of Diseases, tenth revision (ICD-10) in Japan, in
      1995. However, it remains unclear whether the validity of IHD diagnosis improved
      after this revision. METHODS: We conducted the Oita Cardiac Death Survey to
      validate IHD certified deaths that occurred among residents aged 25-74 in Oita
      City, Japan (mean population = 273,000). Of the eligible 342 fatalities, 328
      cases (95.0%) were examined by a review of the medical records and/or interviews
      with physicians. The MONICA criteria were applied and provided a reference
      standard against which to assess the validity of certified fatal IHD. Sensitivity
      (Se), positive predictive value (PPV), specificity (Sp) and negative predictive
      value (NPV) for IHD as the cause of death were analyzed, assuming that all
      validated IHD deaths were true. Multivariate logistic models were used to
      determine associations of false positive and false negative cases with sex, age
      at time of death and place of death. RESULTS: Vital statistics revealed 273
      fatalities to be due to cardiac disease, including 143 from acute myocardial
      infarctions (AMI), 27 from other IHD, 52 from heart failure and 51 from other
      heart diseases. After validation, 25 'definite fatal AMI' and 71 'possible fatal
      AMI or IHD death' were identified among all subjects according to the MONICA
      criteria. In all, Se, PPV, Sp and NPV for IHD certified as the cause of death
      were 86.5% (95% Cl: 77.6-92.3), 50.3% (42.5-58.1), 64.7% (58.1-70.7), and 92.0%
      (86.5-95.5), respectively. PPV among persons aged 25-54 years was remarkably
      decreased. PPV and Sp among out-of-hospital deaths were significantly lower than
      for in-hospital deaths. Multivariate logistic models revealed out-of-hospital
      deaths and being aged 25-54 years to be significant predictors of false positive
      cases (odds ratio (OR) = 2.03, P < 0.001 versus in-hospital deaths and OR = 2.79,
      P < 0.05 versus ages of 65-74 years, respectively). CONCLUSIONS: Because false
      positive cases increased among certified IHD deaths after the revision, PPV and
      Sp percentages decreased. Out-of-hospital deaths and being aged 25-54 years were
      associated with increased possibility of false positive. Given our findings, IHD
      deaths in vital statistics may increase due to the tendency of physicians to
      certify IHD as the cause of death in cases without clear sign suggestive of other
      causes.

PMID- 11579483
TI  - [The influence of lifestyle and night-shift work on sleep problems among female
      hospital nurses in Japan].
AB  - STUDY OBJECTIVE: In this study, by conducting a questionnaire survey, we aimed to
      clarify the situation regarding sleep disorders in female hospital nurses and
      their relation with night-shift work and lifestyle. METHODS: The subjects were
      female nurses working at 5 hospitals, each with more than 400 beds. The survey
      was carried out in July 2000. The questionnaire contained six items concerning
      sleep quality from the Pittsburgh Sleep Quality Index (PSQI), two new items on
      sleep drafted by ourselves, and some questions on lifestyle and shift-work
      status. RESULTS: Among all female nurses, statistically significant differences
      were observed between those working and those not working night shifts for 7
      items regarding sleep (P < 0.05). Significant correlations were observed between
      sleep disorders and the following factors: (1) working night shift, (2) having
      anxiety or stress, (3) getting less than 6 hours of sleep, (4) working in cities,
      (5) having children, and (6) bathing more than 1 hour before going to bed. In
      addition, significant correlations were observed between getting less than 6
      hours of sleep and the following factors: (1) being 40 years of age or older, (2)
      working in cities, and (3) having anxiety or stress. CONCLUSIONS: The results of
      this study suggest that sleep problems among nurses are associated not only with
      night-shift work but also with lifestyle. They also suggest that nurses who work
      night shifts, especially in Tokyo, should try to get sufficient hours of sleep to
      ensure good quality of sleep.

PMID- 11579485
TI  - [An attempt to estimate geographical accessibility to day service facilities
      among the elderly with a geographical information system].
AB  - OBJECTIVE: The objective of this study was to assess inequality in geographical
      accessibility to day service among the elderly in a municipality using a
      geographical information system (GIS). We also examined problems in measuring
      geographical accessibility and ways to validate results. METHODS: The target was
      Hachioji City. The following two data sets were constructed: a data set for day
      service facilities for all of Hachioji City and a data set for the people aged 65
      and over, living within 1 km meshes in Hachioji City. These were integrated and
      displayed on a digital map with GIS software. Geographical accessibility was
      estimated by measuring the shortest road distance from the center point of each
      mesh to day service facilities. RESULTS: There were 47 day service facilities
      serving Hachioji City in October, 2000 and 139 meshes that had elderly residents.
      Their center points were all located within Hachioji City, which was estimated to
      have 73,760 elderly in 2000. The mean distance from the center point of each mesh
      to the nearest day service facility was 1.99 km (SD = 1.75, max = 9.21, min =
      0.03). The proportions of the elderly who had 5 or more facilities within 3 km
      and 5 km from their residence were estimated to be 57.3% and 96.4%, respectively.
      CONCLUSIONS: The results of this study suggest that there is variation in
      geographical accessibility to day service facilities among the elderly living in
      a relatively large municipality. It is now necessary to examine whether the
      difference in geographical accessibility to day service affects the service
      utilization.

PMID- 11579484
TI  - [Association between the interleukin 1B (C-31T) polymorphism and Helicobacter
      pylori infection in health checkup examinees].
AB  - PURPOSE: Associations between Helicobacter pylori (HP) infection and lifestyle
      factors have been demonstrated by several studies, but there are very few reports
      on links with host factors, especially concerning genetic polymorphisms for
      inhabitants of large city. The present investigation was conducted to determine
      the HP infection rate with reference to the Interleukin-1 beta gene (IL-1B)
      polymorphism and assess the interactions with smoking reported for outpatients.
      METHOD: The subjects were 468 participants in a health-check-up program of law of
      health for aged conducted by Nagoya Nishi Health Center. The participants were
      asked to permit use of their residual blood drawn during a health-check-up
      program and written informed consent was obtained for gene polymorphism tests.
      Data on smoking habit were obtained by self-administered questionnaire. The IL-1B
      C-to-T polymorphism at -31 was genotyped by PCR-CTPP (polymerase chain reaction
      with confronting two-pair primers) and an anti-HP IgG antibody test was used for
      detecting HP infection. Differences in values were assessed by a chi 2 test. An
      unconditional logistic model was applied for estimating odds ratios with the
      computer program STATA Version 6. This study was approved by the Ethical
      Committee at Aichi Cancer Center in 2000 before it was commenced (Ethical
      Committee Approval Number 11-12) RESULTS: The HP infection rate was 52.6%
      (61/116) for the C/C genotype of IL-1B-31, 48.6% (89/183) for the C/T, and 63.2%
      (103/163) for T/T; the difference were not statistically significant. However,
      when non-current smokers were excluded, the rate were 47.8% (11/23), 52.9%
      (18/34), and 72.7% (16/22), respectively, indicating the T/T genotype to have a
      higher infection rate. The age-sex-smoking adjusted odds ratio (OR) relative to
      the C/C genotype were 0.97 (95% confidence interval, 0.59-1.57) for the T/C
      genotype and 1.73 (1.04-2.87) for the T/T genotype. Among current and former
      smokers the age-sex adjusted OR were 1.68 (0.50-5.71) for the T/C genotype and
      5.29 (1.11-25.1) for the T/T genotype, suggesting a effect of this polymorphism
      prominent in smokers. CONCLUSION: An association between the IL-1B-31
      polymorphism and persistent HP infection was observed for inhabitants with a
      smoking habit, indicating that this polymorphism is one genetic trait conferring
      an increased likelihood of persistent HP infection.

PMID- 11579486
TI  - [The problems of prenatal diagnosis. The survey of attitude and consciousness of
      the pregnant women in Sapporo].

PMID- 11579487
TI  - [Pathobiology of severe acute pancreatitis].

PMID- 11579488
TI  - [Evidence-based review of the literatures in the management of acute
      pancreatitis].

PMID- 11579490
TI  - [Clinical features in six patients with liver abscess caused by Streptococcus
      milleri].
AB  - Among 39 patients with pyogenic liver abscess who were admitted to our institute,
      six (15%) were infected by Streptococcus milleri (S. milleri). We investigated
      clinical features of these six patients. There were five males and one female,
      aged 43-81 years old (mean: 61). Five of the six patients had underlying illness.
      All patients had fever, and three of them complained of abdominal pain. Three
      patients had mixed infections; particularly intraoral anaerobes, Fusobacterium,
      were found in two of the three patients. There were no differences in clinical
      features between patients with S. milleri liver abscess and those with other
      bacterial liver abscess. In conclusion, on selecting antibiotics for the
      treatment of liver abscess, it is necessary to consider the S. milleri and
      intraoral anaerobes.

PMID- 11579489
TI  - [Induction of mucosal immunity to mycobacterial heat shock protein (hsp) 65 by
      colonic inoculation of plasmid DNA encoding hsp65].
AB  - Mycobacterial heat shock protein (hsp) 65 has more than 50% sequence homology
      with human hsp60 and immune responses against mycobacterial hsp65 may cross-react
      with human hsp60 and could cause autoimmune diseases including inflammatory bowel
      diseases (IBD). Since the colonic mucosa is a main inflammatory site in IBD,
      mucosal immunity to hsp65 may be more important for the mucosal inflammation than
      systemic immunity to hsp65. We inoculated plasmid DNA (pDNA) encoding
      mycobacterial hsp65 (pACB-hsp 65) into the colon of Wistar rats and evaluated the
      mucosal humoral immune response and the effect of these immune responses on the
      colonic mucosa. Four weeks after pDNA inoculation, significantly elevated titers
      of hsp65-specific IgA antibody were seen in fecal extracts of rats immunized
      intra-colonic mucosa with pACB-hsp65 (40 +/- 9 U/ml), whereas the fecal IgA
      antibody titers of rats inoculated intradermal with pACB-hsp65 did not arise (8
      +/- 5 U/ml). Colonic inoculation of pACB-hsp65 induced systemic and mucosal
      immune responses to hsp65. However, macroscopic and histological examinations of
      the colonic mucosa inoculated with pACB-hsp65 showed no evidence of mucosal
      damage. These results suggested that the mucosal immunity to hsp65 on the colonic
      mucosa may not play a crucial role in the induction of colonic mucosal
      inflammation as was seen in IBD.

PMID- 11579491
TI  - [A case of esophageal superficial adenocarcinoma arising from esophago-gastric
      junction].

PMID- 11579492
TI  - [A case of gastric hypertrophy after ingestingraw firefly squid probably due to
      type x larvae of the suborder spirurina involvement].

PMID- 11579493
TI  - [A case of fulminant amebic colitis with feature of pseudomembrane formation on
      sigmoidscopic examination].

PMID- 11579494
TI  - [A case of portal hypertension secondary to arteriovenous malformation involving
      the inferior mesenteric vessels].

PMID- 11579495
TI  - [A case of advanced hepatocellular carcinoma (Vp3) with right adrenal gland
      metastasis successfully treated with repeated arterial infusion chemotherapy
      using low dose CDDP and 5-FU through an implanted reservoir].

PMID- 11579496
TI  - [A case of small pancreatic cancer that was difficult to identify as a pancreatic
      mass].

PMID- 11579497
TI  - [A case of nonsteroidal anti-inflammatory drugs (NSAIDs) induced colitis].

PMID- 11579498
TI  - [Requirements for early discharge after allogeneic bone marrow transplantation].
AB  - To assess the requirements for early discharge after allogeneic bone marrow
      transplantation (BMT), we evaluated infectious complications and transplantation
      related toxicity (TRT) among 46 recipients who underwent allogeneic BMT between
      January 1997 and August 1999 at our institute. Acute graft-versus-host disease
      (GVHD) and cytomegalovirus (CMV) antigenemia developed in 29 and 26 patients,
      respectively. More than 95% of the episodes occurred before day 70. Among the
      patients without CMV antigenemia and without prednisolone (PSL) therapy for acute
      GVHD (n = 15), only 3 developed TRT or infections (pneumonia, varicella zoster
      virus infection and hemolytic uremic syndrome), but all of these episodes were
      cured without fatality. On the other hand, in patients with CMV antigenemia
      and/or PSL therapy for acute GVHD, a high incidence of TRT and infectious
      complications was observed until day 180, and some of these episodes were fatal.
      In conclusion, discharge on day 70 after allogeneic BMT seems to be safe for
      patients who do not develop CMV antigenemia or receive PSL therapy for acute
      GVHD.

PMID- 11579499
TI  - [Protein S deficiency in three patients with thrombosis].
AB  - Protein S (PS) deficiency, which is caused by various factors including
      congenital and acquired disorders, is a risk factor for thrombophilia. We
      described 3 patients with different backgrounds, who all exhibited PS deficiency.
      The first patient was a 47-year-old woman who suffered from frequent cerebral
      infarctions, deep-vein thrombosis (DVT) of her lower extremities, and pulmonary
      thromboembolism. Her son suffered from skin necrosis due to PS deficiency and
      both had the same mutant allele of the PS gene. The second patient was a 50-year
      old woman who experienced a cold sensation in her fingers. Her relatives had a
      history of cerebrovascular disease. No mutation was detected in her PS gene. The
      third patient was a 27-year-old man with antiphospholipid antibody. He suffered
      from thrombocytopenia, skin necrosis, DVT of his lower extremities, and pulmonary
      thromboembolism. A mutation was identified in the steroid hormone-binding
      globulin-like (SHBG) domain of his PS gene. Neither his parents nor siblings had
      a history of thrombosis. The mutations found in the first and third patients were
      both missense mutations in the SHBG domain that have not been reported
      previously. The third patient had a mutation in the site that is involved in
      binding to C4b-binding protein, which modifies the immune response. These three
      cases provide key insights into the pathophysiology of PS deficiency.

PMID- 11579500
TI  - [Three cases of malignant lymphoma accompanied by renal cell carcinoma].
AB  - Three cases of malignant lymphoma (ML) accompanied by renal cell carcinoma (RCC)
      are reported. From September 1997 through August 2000, we treated 85 patients
      with ML. Among these patients, three had accompanying RCC (clear cell type): case
      1, a 57-yr-old man with gamma/delta-T cell lymphoma; case 2, a 25-yr-old man with
      Grade 3 follicular lymphoma; case 3, a 64-yr-old man with MALToma of the right
      orbit. Renal cell carcinoma is a relatively rare disease, but several reports
      have indicated that, for some reason, the incidence of concurrent RCC and ML is
      higher than expected. It is possible that the two malignancies share some common
      background factors, such as genetic mutation, immunological abnormality, or an
      immunomodulatory effect of the first tumor. The patient in case 2 was thought to
      have an abnormal immunological background from his medical history, which
      included bronchial asthma, idiopathic thrombocytopenic purpura, and mesangial
      proliferative glomerulonephritis (non-IgA type). Therefore the combination of ML
      and RCC in this patient may have been due to immunological impairment.

PMID- 11579501
TI  - [Aggressive NK cell leukemia/lymphoma: an autopsy case].
AB  - A 67-year-old man was admitted with erythematous skin papules, lymphadenopathy
      and liver dysfunction. The bone marrow was filled with atypical lymphoid cells,
      and a skin biopsy showed diffuse dermal infiltration of neoplastic cells, which
      were positive for CD2, CD8, CD56, TIA-1, Granzyme B and EBER (ISH), but negative
      for CD3, CD4, CD16 and CD57. Molecular analysis showed a germline configuration
      for T-cell receptor beta, gamma chain genes, and monoclonal integration of
      Epstein-Barr virus. The THP-COP regimen was not effective and the patient died of
      severe metabolic acidosis 2 months later. Autopsy revealed diffuse infiltration
      of neoplastic cells in almost all organs. Apoptosis of tumor cells and
      proliferation of hemophagocytic macrophages were remarkable. Neither
      angiocentricity nor necrosis was observed. The findings in this patient were
      indistinguishable from advanced-stage nasal-type NK cell lymphoma. However, the
      diagnosis of aggressive NK cell leukemia/lymphoma may be justified because of the
      marked involvement of the marrow at onset, fulminant clinical course and diffuse
      infiltration of tumor cells evident at autopsy.

PMID- 11579502
TI  - [Splenectomy in 5 patients with idiopathic myelofibrosis].
AB  - Between 1992 and 1999, 5 patients with chronic idiopathic myelofibrosis (MF)
      underwent splenectomy at our hospital. The median age at the time of splenectomy
      was 63 years (range, 58-69 years), while the median interval from diagnosis of MF
      to splenectomy was 38.2 months (range, 3.7-87.2 months). Reasons for splenectomy
      included symptomatic splenomegaly in 5 patients, transfusion-dependent anemia in
      5, and refractory thrombocytopenia in 3. Although most of the patients with
      transfusion-dependent anemia and thrombocytopenia showed some improvement at 1
      month after splenectomy, the response was durable in only 2 patients at 6 months.
      Post-surgical thrombocytosis of 1020 x 10(9)/l was observed in one patient. Blast
      cell counts in peripheral blood increased after splenectomy in 4 patients.
      Leukemic transformation occurred in one patient 5 months after splenectomy. Four
      patients eventually died (2 of infection, 1 of acute myelocytic leukemia, and one
      of heart failure). Overall median survival was 54.7 months (range, 10.9-110.0
      months) and 10.2 months (range, 6.0-33.6 + months) from diagnosis and time of
      splenectomy, respectively. We confirmed the palliative role of splenectomy in
      advanced-stage MF, but sufficient consideration should be given to late
      complications including blastic transformation.

PMID- 11579503
TI  - [Cord blood transplantation with two mismatched HLA loci in a child with acute
      lymphoblastic leukemia in second remission: follow-up of minimal residual disease
      using a clone-specific probe].
AB  - A 9-year-old girl with acute lymphoblastic leukemia in second remission underwent
      cord blood transplantation (CBT) from an HLA-mismatched (2 loci by serotype, 3
      loci by genotype) unrelated donor. The infused nucleated cell count was 1.95 x
      10(7)/kg. FK506 and mini-MTX were used to prevent graft-versus-host disease
      (GVHD), but grade II acute GVHD developed on the skin (stage III). The GVHD
      subsided after administration of corticosteroid, but marked hyperglycemia
      developed, which required transient insulin therapy for its control. Minimal
      residual disease (MRD) was assessed using a clone-specific probe for the JH
      region. MRD was positive before CBT, but became negative one month after CBT.
      Now, at 14 months after CBT, the patient is in a disease-free state without
      detectable MRD. These observations suggest that CBT with two mismatched HLA loci
      can be performed safely, and that sequential analysis of MRD is useful for
      evaluation of the disease status after CBT.

PMID- 11579504
TI  - [Five cases of nonepisodic angioedema with eosinophilia].
AB  - The syndrome of episodic angioedema associated with eosinophilia (EAE),
      originally identified by Gleich et al., is characterized by recurrent attacks of
      angioedema, urticaria, fever, increased body weight, and eosinophilia of unknown
      origin. Five young (aged 23-32 years) female patients were referred to our
      hospital because of eosinophilia (4,900-10,400/microliter). The chief complaints
      in all patients were angioedema and pain in the lower extremities without
      urticaria. Fever and increased body weight were not evident in most of the
      patients. These clinical features resolved spontaneously within 3 months, and no
      recurrence was observed. These characteristics were consistent with nonepisodic
      type EAE (NEAE), which was proposed by Chikama et al. and is observed frequently
      in Japan. The clinical characteristics of NEAE were studied in the present 5
      cases and the 25 cases reported previously in Japan. This revealed some
      additional characteristics: 1) a tendency for occurrence in autumn, 2) arthritis
      and absence of urticaria in some patients, and 3) increased serum LDH levels in
      some cases. It is suggested that NEAE should be treated with antiallergic drugs
      or simply followed without treatment, because spontaneous remission is observed
      frequently.

PMID- 11579505
TI  - [CD7(+) acute myeloid leukemia (M0) associated with a mediastinal bulky mass
      lesion].
AB  - A 41-year-old man visited his doctor in May 2000 because of a sore throat and
      high fever. His symptoms did not improve, despite administration of antibiotics
      and nonsteroidal anti-inflammatory drugs. Since a chest X-ray examination
      revealed an anterior mediastinal bulky tumor, he was referred and admitted to our
      hospital on June 21, 2000. The peripheral white blood cell count was
      44,540/microliter with 74% myeloblasts. Bone marrow aspiration revealed a
      hypercellular marrow with 82% myeloblasts, which were negative for peroxidase and
      alpha-naphthyl butylate esterase staining. Blast cells were positive for CD7,
      CD13, CD33, CD34, and HLA-DR, and negative for CD56. A needle biopsy specimen of
      the mediastinal tumor consisted of myeloblasts. We diagnosed the patient as
      having CD7 (+) acute myeloid leukemia (AML) (M0) with a bulky mediastinal mass
      based on the surface marker analysis, although the clinical features resembled
      myeloid/NK precursor acute leukemia. The patient achieved a complete remission
      after two courses of induction therapy. We are planning an allogeneic stem cell
      transplantation during his first remission because of the high risk of relapse.

PMID- 11579506
TI  - [Philadelphia chromosome-positive acute lymphoblastic leukemia preceded by acute
      pleuropericarditis].
AB  - A 69-year-old woman was admitted with sudden chest pain and high fever.
      Electrocardiography showed negative T waves in the precordial leads.
      Subsequently, pleural and pericardial effusion developed, but the symptoms and
      signs subsided without specific therapy. On day 31, fever, left shoulder pain and
      pleural effusion reappeared. 67Ga scintigraphy showed abnormal uptake in the
      chest and left shoulder. Blasts were detected in the peripheral blood on day 44,
      and in the pleural effusion and bone marrow on day 45. The blasts were positive
      for Philadelphia chromosome, CD10, CD19, CD33, CD34 and IgH-chain rearrangement
      and negative for myeloperoxidase. The clinical picture of the preceding
      pleuropericarditis was that of viral or idiopathic origin, but its relationship
      with acute lymphoblastic leukemia was unclear. Inflammatory chemokines in the
      pleural space may have induced invasion of the leukemic cells.

PMID- 11579507
TI  - [Successful second transplant from one-locus HLA-mismatched unrelated donor for
      graft rejection following initial transplant from another unrelated donor in a
      patient with chronic myelogenous leukemia].
AB  - We report a patient with chronic myelogenous leukemia who received a second
      transplant from a one-locus HLA-mismatched unrelated donor after rejection of an
      initial bone marrow graft. For the first transplant, HLAs were fully matched,
      conditioning with busulfan + cyclophosphamide (CY) was applied, and cyclosporin A
      + short-term methotrexate (sMTX) was used for prophylaxis against GVHD. A
      complete chimera was not obtained, and the graft was rejected on day 122. For the
      second transplant, there was a one-HLA locus (DR) mismatch, conditioning was done
      with total body irradiation + cytarabine + CY, and GVHD prophylaxis consisted of
      FK506 + sMTX. Engraftment was obtained on day 27, and no graft failure was
      occurred at the time of writing. This case suggests that strong immunosuppression
      may have prevented rejection of the second bone marrow graft.

PMID- 11579508
TI  - IL-12 and IL-18 synergistically induce the bactericidal activity of murine
      peritoneal cells against M. leprae.
AB  - We examined the effect of IL-12 and IL-18 on bactericidal activities of mouse
      peritoneal cell (PC) against Mycobacterium leprae (M. leprae). We demonstrated
      that IL-12 and IL-18 synergistically induced the NO-dependent bactericidal
      activity of PC by stimulating Natural Killer (NK) cells and T-cells through IFN
      gamma production. IL-12 and IL-18 induced host cell death through NK-cells and T
      cells. Therefore. IL-12 and IL-18 play an important role on direct killing of
      intracellular M. leprae and on indirect killing of them through inducing host
      cell death.

PMID- 11579509
TI  - [In vitro induction of differentiation from embryonic stem cells: looking forward
      to regenerative medicine].
AB  - Embryonic stem (ES) cells are pluripotential cells, and enable us to study
      mechanisms of cell differentiation. Gene disruption of ES cells by homologous
      recombination is to be clear the function of targeted genes. Recently, it has
      been reported that bone marrow hematopoietic stem cells have a potential to
      differentiate into neuronal cell, muscle cell, liver cell, epidermal cell, and
      also epithelial cell lineages. Moreover, cloned animals from somatic cell nuclei
      were produced. Here, we show osteoclastogenesis, and endothelial cell-genesis
      from single ES cell, and discuss the possibility for organogenesis in vitro.
      Furthermore, we would like to summon to understand usefulness and dangerousness
      of the regenerative medicine.

PMID- 11579510
TI  - [Reasons why Mycobacterium leprae cells do not multiply under the cell-free
      condition].
AB  - Our previous paper reported that the intracellular ATP content in cells of M.
      leprae consistently increased in the medium containing adenosine after 4-6 weeks
      of cultivation and decreased thereafter. The reason why ATP generation ceased 4-6
      weeks after cultivation is not clear, but it was determined that the termination
      in ATP generation was not a result of deterioration in the culture medium during
      cultivation because a renewal trial of the old culture medium by freshly prepared
      culture medium had no effect further maintenance or progressive increase in ATP
      generation. From the results obtained in a renewal trial of the culture medium, I
      would like to speculate that the reason why M. leprae cells do not multiply in
      vitro might be due to the characteristic property of the cell wall of M. leprae,
      i.e., fragility.

PMID- 11579511
TI  - [Genome features of Mycobacterium leprae].
AB  - Recent studies have revealed that the Mycobacterium leprae genome contains many
      pseudogenes. This short review summarizes the structural features of the M.
      leprae genome and genes.

PMID- 11579512
TI  - [A morphological study of nerve biopsies in leprous neuropathy].
AB  - Peripheral nerve biopsies from 10 leprosy patients(6 tuberculoid patients and 4
      lepromatous patients) were studied morphological aspect. Light microscopical
      examination showed that the perineurium was markedly thickened by infiltrated
      cell in tuberculoid type and Mycobacterium leprae in lepromatous type. Schwann
      cell markedly decreased in number, and nerve fiber disappeared without
      regeneration in severe cases. In mild cases, subperineurial edema was present.
      The nerve fiber density was normal or mild decreasing. Ultrastructural
      examination showed abnormality of basal lamina on perineurial cells. The basal
      lamina of the perineurium completely disappeared in severe cases, and showed
      splitting even if the perineurium had normal structure in light microscopy. Both
      type of leprous neuropathy had same pathological changes in regard to abnormality
      of the basal lamina. There were many M. leprae presented in Schwann cells,
      fibroblasts and perineurial cells on the nerve of lepromatous patients, although
      few M. leprae in the nerve of tuberculoid patients. This study provides that
      these abnormality of perineurium is characteristic in both types of leprous
      neuropathy.

PMID- 11579513
TI  - [Clinical leprosy in Japan].
AB  - The Leprosy Prevention Law was abolished at the end of March, 1996. Since medical
      insurance for leprosy started in April, 1996, dermatologists in clinics have to
      take care of leprosy patients. However, dermatologists have not learned enough
      about leprosy, and only a few of them are familiar with it. Japanese patients
      newly diagnosed with leprosy in Japan have decreasing, and patients who come from
      foreign countries to work in Japan have more important in leprosy control.
      Therefore, it is important to educate dermatologists about leprosy. Recently,
      diagnostic guides including information about network systems have become
      available in book stores. It is possible to obtain all kinds of information about
      leprosy from the network systems.

PMID- 11579514
TI  - [Chemotherapy of leprosy: theoretical basis of new guideline in Japan].
AB  - For the effective treatment of leprosy, we should consider that (1) more time is
      needed for the elimination of bacilli than ordinary bacterial infection, (2)
      bactericidal therapy often induces host immunity called reactions, (3) rapid
      treatment is needed for the reactions. Last year, ad hoc committee of Japanese
      Leprosy Association recommends standard treatment protocol of leprosy in Japan,
      which is a modification of World Health Organization's multidrug therapy. For
      multibacillary(MB) with bacterial index (BI > or = 3) before treatment, 2 years
      treatment by rifampicin, dapsone and clofazimine (MDT/MB) is necessary. When BI
      decrease is not satisfactory(BI value decrease < 2 steps, or final BI > or = 3)
      after 2 years, MDT/MB should be continued until BI negativity and loss of active
      lesions. Theoretical background of our proposal is described.

PMID- 11579515
TI  - [Medical malpractice in allergic disease].

PMID- 11579516
TI  - [Modification evil drug of topical steroid and atopy business].

PMID- 11579517
TI  - [The relationships between the prevalence of asthmatic symptoms and environmental
      factors].
AB  - The relationships between the prevalence of asthmatic symptoms and environmental
      factors were evaluated using a modified version of the Japanese ATS-DLD
      children's questionnaire. The questionnaire was distributed to 13,306 students in
      3 areas of Yokohama City; in 1986 (4705), 1988 (4440), and 1991 (4161). The
      results indicate: 1. The prevalence of asthmatic symptoms among boys increased
      slightly from 1986 (9.2%) to 1991 (9.6%), but no increase was observed that among
      girls (5.7%). The overall prevalence among boys was 1.7 times higher than that
      among girls. 2. On the whole, the air pollution level was Tsurumi-ku > Naka-ku >
      Midori-ku. But the prevalence of asthmatic symptoms among boys was Naka-ku >
      Tsurumi-ku > Midori-ku in 1986, 1988 and 1991. The prevalence among girls was the
      same result in 1986, but in 1988 and 1991, it was Tsurumi-ku > Naka-ku > Midori
      ku. 3. In the longitudinal study of the same group, the prevalence of asthmatic
      symptoms among boys decreased between 5th and 6th grade. In contrast, remission
      of asthma increased between 5th and 6th grade. And the prevalence of asthmatic
      symptoms among girls decreased between 3rd and 6th grade. In contrast, remission
      of asthma increased between 3rd and 6th grade. 4. Children who had a personal or
      family history of allergic diseases, allergic disposition, respiratory diseases
      before 2 years old, wheezing or difficulty in breathing, or allergies against
      foods or medicines, showed a statistically significant Odds ratio (p < 0.01) for
      asthmatic symptoms.

PMID- 11579518
TI  - [QOL questionnaire version 2001 for pediatric patients with bronchial asthma and
      their parents or caregivers--preparation and evaluation].
AB  - We already reported that the QOL questionnaire for pediatric patients with
      bronchial asthma and their parents or caregivers reflects reliability (including
      test retest), factorial validity, and changes in paroxysmal attacks of asthma. In
      this study, we revised the questionnaire for use in routine medical care. We
      investigated the importance of questions for affected children and their parents
      or caregivers and selected and discarded questions on the basis of average ranks
      of the importance and medical standpoint so that the questionnaire might have
      physical and emotional domains. The QOL questionnaire version 2001 for pediatric
      patients with bronchial asthma and their parents or caregivers (hereafter to be
      abbreviated as the version 2001) includes 15 questions for patients under the age
      of 4 years and 20 questions for patients over the age of 4 years and 4 year-old.
      The "present" and "absent" groups, which were categorized with respect to the
      events (e.g., attack) that developed in 2 weeks prior to the QOL investigation,
      showed a significant difference (Mann-Whitney U-test) in terms of the total score
      of replies which constitute each domain, i.e., physical domain (p = 0.0052) in
      patients under the age of 4 years and physical domain (p < 0.0001) and emotional
      domain (p < 0.0001) in patients over the age of 4 years and 4 year-old. Regarding
      the average value of each reply which constitutes the domain as well, the
      physical domain showed a decrease in symptom instability and the "> or = 4 years"
      group showed a decrease in exertional load and mental load. Therefore, a QOL
      investigation like ours which investigates disorders in which attacks develop
      suddenly, e.g., asthma, should examine the presence or absence of all events
      prior to the investigation. The version 2001 was considered useful for affected
      children and their parents or caregivers to comprehend the content and severity
      of impairments which were provoked by asthma.

PMID- 11579519
TI  - [Chronotherapy of bronchial asthma: circadian rhythms in peak expiratory flow.
      The report II: Circadian rhythms of peak expiratory flow in asthmatic patients
      and effect of sustained-release theophylline on various types of the circadian
      rhythms].
AB  - We monitored peak expiratory flow (PEF) in outpatients with adult bronchial
      asthma in 17 sites in Chiba prefecture 4 times daily for 2 weeks, using a peak
      flow meter to categorize the patients by circadian patterns of PEF. Then a
      sustained-release theophylline preparation formulated for once-daily dosing was
      administered to these patients grouped to examine the effect of the drug on
      circadian rhythms in PEF. Analysis was performed in 215 of total 245 patients
      enrolled as a result of excluding 30 ineligible patients. 187 patients (87.0%)
      exhibited a certain rhythm in their PEF, and 28 patients (13.0%) did not show any
      particular rhythm. These 187 patients with a certain rhythm in PEF were grouped
      into 63 patients (29.3%) of morning-dip type, 83 patients (38.6%) of peak type, 7
      patients (3.3%) of evening-dip type, and 34 patients (15.8%) of flat type. And
      there were no trough-type patients. Uniphyl tablets were administered once a day
      at a daily dosage of 400 mg after supper to 124 patients of the above 187
      patients grouped according to circadian patterns of PEF. Uniphyl was particularly
      effective in the morning-dip type and the peak type. This result suggests that it
      is necessary to take circadian rhythms of PEF into consideration in drug therapy
      for patients with bronchial asthma.

PMID- 11579520
TI  - [The relation between the severity of bronchial asthma and the treatment points
      in children].
AB  - The treatment points and score for definition of the asthma severity were
      initially introduced in the guideline for pediatric asthma treatment and
      management on 1998. We studied the relationship between the severity of clinical
      symptoms for children with bronchial asthma and the treatment points from July
      1998 to November 1999 in our hospital. One hundred twenty five patients (one to
      15 years of age, 77 boys and 48 girls) were retrospectively investigated. The
      treatment points and scores were associated with the clinical symptom score.
      However, there was no relationship in some patients. In order to define the
      severity of bronchial asthma, we should investigate not only the severity in
      terms of the clinical symptoms; the number and degree of asthma attacks, but also
      the treatment points and score. Furthermore, we should pay attention to the
      seasonal variation of the treatment points.

PMID- 11579521
TI  - [A clinical case of bronchial asthma with atelectasis of bilateral upper lobes-
      rheological analysis of the sputum].

PMID- 11579522
TI  - [Usefulness of three-dimensional color Doppler sonography for the differential
      diagnosis of subpleural lesions].
AB  - The purpose of our investigation was to assess the usefulness of three
      dimensional color Doppler sonography (velocity mode and power mode) for the
      differential diagnosis of subpleural lesions. Thirty lesions (11 pneumonias, 5
      lung abscesses, 11 primary lung cancers, 3 metastatic lung cancers) were
      examined. Three-dimensional images were reconstructed by a maximum intensity
      projection method. Three-dimensional representations of intralesional blood flow
      became available for all lesions approximately 11 seconds after scanning. In
      every case, the entire vasculature of the tumor, the pneumonia, the abscess, or
      the inflamed region of the lung was appreciated more easily from three
      dimensional images than from two-dimensional images. We classified the color flow
      pattern of subpleural lesions depicted by color flow imaging into seven groups.
      Color flow was depicted better by the three-dimensional color Doppler power mode
      than the velocity mode. Three-dimensional color flow patterns observed in power
      mode, patterns of the pneumonias and the lung cancers differed significantly. Our
      results suggest that the three-dimensional color Doppler power mode is useful for
      the differential diagnosis of subpleural lesions.

PMID- 11579523
TI  - [Use of expectorated sputum to assess airway inflammation of smoking and its
      cessation].
AB  - To investigate the usefulness of expectorated sputum in the assessment of airway
      inflammation by smoking. I examined cytokine expression in the sputum of healthy
      smokers and non-smokers, and compared them before, and at 8,12 and 16 weeks
      after, cessation of smoking. Four cytokines, interleukin (IL) 8, interferon (IFN)
      gamma, tumor necrosis factor (TNF)-alpha, and IL-10, were assessed by
      immunohistochemistry. In smokers, the percentage of bronchial epithelial (BE)
      cells and macrophages with high intracellular contents of the pro-inflammatory
      cytokines IL-8, IFN-gamma and TNF-alpha, were significantly increased in
      comparison with non-smokers. In contrast, expression of IL-10 was significantly
      decreased in smokers. After smoking cessation, expression of IL-8 was
      significantly decreased by the 16th week, that of IFN-gamma was significantly
      decreased by the 12th to the 16th week, but that of TNF-alpha was unchanged even
      at 16 weeks post-cessation, and that of IL-10 was significantly increased at that
      time. Cytokine expression in BE cells was similar to that in macrophages. From
      the data, we concluded that expectorated sputum is useful for assessing airway
      inflammation due to smoking and for following the series of changes that follow
      smoking cessation.

PMID- 11579524
TI  - [HRCT findings for four cases of measles pneumonia].
AB  - Although, in Western countries, adult-onset pneumonia that is associated with
      measles is not rare, reports of its incidence in Japan have been sparse. Among
      eight adolescent and adult (16-34-year-old) measles patients hospitalized in
      National Sanatorium Tsuruga Hospital, we found four in whom chest radiography and
      CT revealed pneumonia. The high-resolution lung CTs of these patients revealed
      features differing from those characteristic of bacterial pneumonia: bronchial
      wall thickness, centrilobular nodules in ground glass opacity, interstitial
      lesions (interlobular septal thickening, fissure thickening, pleural effusion)
      and lymphadenopathy. Of these findings, the centrilobular nodules in ground glass
      opacity were marked in these cases, and so this may be the most prominent finding
      in measles pneumonia; and furthermore, since interlobular septal thickening has
      not been reported in mycoplasma pneumonia or other atypical pneumonias, it may
      indicate a measles-specific, virus-induced pneumonia.

PMID- 11579525
TI  - [A case of pulmonary capillary hemangiomatosis].
AB  - In March 1995, a 54-year-old woman was admitted to a hospital because of
      exertional dyspnea and her condition was diagnosed as primary pulmonary
      hypertension. In September 1996, respiratory difficulty and hemosputum were
      woted. The chest computed tomographic scan showed diffuse micronodular opacities,
      and she was admitted to our hospital for examination of other pulmonary
      conditions giving rise to pulmonary hypertention. However no lung biopsy could be
      performed, because the pulmonary arterial pressure was too high. Although the
      patient received medication, she died of progressive right heart failure. The
      pathological diagnosis at autopsy was pulmonary capillary hemangiomatosis (PCH).
      Although PCH is a very rare disease that causes secondary pulmonary hypertension,
      it is important to distinguish it from primary pulmonary hypertension and
      pulmonary veno-occlusive disease.

PMID- 11579526
TI  - [A case of post-tuberculosis chronic empyema with effective low-dose, long-term
      clarithromycin administration].
AB  - A 78-year-old woman with post-tuberculosis chronic empyema who underwent
      unsuccessful decortication in July 1993, was admitted to our hospital in November
      1994 because of M. tuberculosis in her sputum. One month after anti-tuberculosis
      treatment, the M. tuberculosis disappeared from the sputum, but a pleurocutaneous
      fistula that exuded abundant bloody pus containing Pseudomonas aeruginosa
      persisted in the area of chronic empyema. In July 1997, 200 mg of clarithromycin
      (CAM) was administered daily; 21 months later, the pus and pleurocutaneous
      fistula had disappeared. Post-tuberculosis chronic empyema with a fistula is
      generally an intractable condition that necessitates surgery. In this case, the
      empyema did not improve during the 4 years after the surgery. However, low-dose,
      long-term CAM administration brought about a disappearance of pus from the
      fistula and closure of the empyema spaces.

PMID- 11579527
TI  - [A case of systemic fat embolism in mixed connective tissue disease associated
      with interstitial pneumonia during steroid treatment].
AB  - A 67-year-old man with a four-year history of mixed connective tissue disease
      (MCTD) associated with interstitial pneumonia was admitted to our hospital with a
      complaint of dyspnea and moist cough. Because the interstitial pneumonia was
      exacerbated, he was given high-dose steroid treatment (pulse therapy and
      sequential oral treatment of PSL 50 mg/day). After treatment his general
      condition showed some improvement, but then he suddenly died of acute respiratory
      failure. Autopsy disclosed fat emboli in the lungs, kidneys, liver and
      myocardium. The fat embolism may have been a consequence of the steroid
      treatment. Fat embolism should be taken into account as one of the causes of the
      acute respiratory failure in collagen vascular disease patients receiving steroid
      treatment.

PMID- 11579528
TI  - [A case of relapsing polychondritis monitored by daily peak flow measurement].
AB  - A 55-year-old man was admitted to our hospital with dyspnea and stridor. At
      presentation, he also had a low grade fever, arthralgia and nasal obstruction.
      His chest roentgenogram showed diffuse tracheal narrowing, and chest CT revealed
      a thickened tracheal wall and fractured cricoid and thyroid cartilages. A
      diagnosis of relapsing polychondritis was made on the basis of his symptoms and
      in accordance with Damiani's criteria and CT findings. Daily peak flow (PEF)
      monitoring was carried out to assess the disease condition of the trachea.
      Methylprednisolone pulse therapy was started, and was followed by oral
      prednisolone, which improved his condition immediately, but reduction of oral
      prednisolone led to recurrence. The clinical course was clearly evaluated by PEF
      monitoring, but the change was undetectable on chest CT. Dapson,
      cyclophosphamide, and inhaled steroid were administered with oral prednisolone
      and the patient's condition has since been fair and stable. PEF monitoring may be
      useful for the early detection of recurrence in cases of relapsing
      polychondritis.

PMID- 11579529
TI  - [Pneumonia caused by Nocardia nova].
AB  - This is the first clinical report of a case of pneumonia caused by Nocardia nova
      in Japan. A 52 year-old woman who had received steroids and cyclophosphamide for
      six years because of polymyositis was admitted to our hospital for further
      examination. On admission she had a mild cough, and her chest radiography and
      computed tomography revealed bilateral multiple nodules, some of which were
      cavitated. She developed a cough productive of yellow sputum and fever up to 38
      degrees C. Examination of the sputum revealed a gram-positive branched organism
      and sputum cultures repeatedly grew Nocardia species. The isolate was identified
      as Nocardia nova later. Clinical recovery was obtained readily upon treatment
      with imipenem and trimethoprim methoxazole, though the latter drug was
      discontinued because of nausea and anorexia. This drug was therefore replaced
      with oral minocycline, which proved to be ineffective clinically although
      susceptibility testing of the drug showed positive sensitivity. Minocycline was
      replaced with clarithromycin, after which chest radiography and computed
      tomography showed almost total resolution of the infiltrates. Clarithromycin may
      be an alternative oral agent to sulfonamides or minocycline when these agents are
      ineffective or not tolerated.

PMID- 11579530
TI  - [Elderly-onset anticentromere antibody-positive pulmonary-renal syndrome: report
      of an autopsy case].
AB  - We report an autopsy case of elderly-onset anticentromere antibody-positive
      pulmonary-renal syndrome. An 84-year-old woman was admitted to our hospital with
      complaints of leg edema and general malaise. Neither skin rush nor arthritis was
      seen. Because of hematuria, proteinuria with various casts, renal dysfunction and
      anemia, a clinically diagnosis of rapidly progressive glomerulonephritis was
      made. Slight pulmonary hypertension was observed in ultrasonic cardiography.
      Hypocomplementemia was not seen. Tests for MPO- and PR 3-anti-neutrophil
      cytoplasmic antibodies and anti-glomerular basement membrane antibody were
      negative, but a high titer of antinuclear antibody with a discrete speckled
      pattern on immunofluorescent staining was disclosed. Results for anticentromere
      antibody and anti-Ki antibody were positive, but for anti-Sm antibody and anti
      double stranded DNA antibody were both negative. She did not present any clinical
      features of systemic sclerosis or CREST syndrome. Subsequently, prednisolone was
      administered, but pulmonary alveolar hemorrhage occurred and the patient died of
      acute respiratory failure caused by massive pulmonary hemorrhage. Autopsy
      revealed crescentic glomerulonephritis including glomerular capillaritis and
      pulmonary capillaritis with positive granular deposits of immunoglobulins and
      compliment on the glomerular and pulmonary capillary walls. Immunologically
      mediated crescentic glomerulonephritis and pulmonary capillaritis was then
      diagnosed histopathologically. The main pathological feature of the case was
      small-vessel vasculitis with immune-complex deposition. Although this case did
      not fulfill the clinical criteria for systemic lupus erythematosus (SLE), its
      histological features resembled those of lupus nephritis and acute lupus
      pneumonitis. We speculated that anticentromere antibody-positive pulmonary-renal
      syndrome without any other symptoms or signs of connective tissue disease, such
      as our case, is a clinical entity distinct from typical SLE or CREST syndrome.

PMID- 11579531
TI  - [Subacute cor pulmonale due to microscopic pulmonary tumor embolism].
AB  - We report a case of subacute pulmonary hypertension caused by microscopic
      pulmonary tumor embolism due to the dissemination of gastric cancer cells. The
      patient, a 61-year-old man with no history of malignant diseases, was admitted to
      our hospital on October 14 in 1998 because of cough and dyspnea on effort, that
      had developed since the previous month. On admission, chest radiography including
      CT scans showed slight cardiomegaly and disseminated reticulonodular shadows
      predominating in the lower lung fields of both lungs, and arterial blood gas
      analysis disclosed severe hypoxemia. Lung perfusion scintigraphy revealed
      multiple irregular defects in both lungs. Echocardiography indicated right
      ventricular overload, and the pulmonary artery systolic pressure was estimated to
      be higher than 80 mmHg. Disseminated intravascular coagulation (DIC) developed on
      the 6th day of hospitalization. Multiple pulmonary embolism with DIC of unknown
      cause was diagnosed, and the patient was given anticoagulant therapy with
      heparin. However, he died of respiratory failure on the 7th day of
      hospitalization. At autopsy, an invasive cancer was found in the stomach,
      resembling type IIc early gastric cancer. The lumens of the pulmonary arterioles
      were significantly narrowed by fibrocellular proliferation and thrombi
      accompanying tumor cell clusters, and some of the microvessels were completely
      occluded. Disseminated microscopic pulmonary metastasis of malignant tumors
      should be included in the differential diagnosis of subacute pulmonary
      hypertension due to multiple pulmonary embolism of unknown cause.

PMID- 11579532
TI  - [A case of acute progressive pulmonary cystic disease associated with
      Pneumocystis carinii pneumonia in a non-HIV-infected patient].
AB  - We report a case of Pneumocystis carinii pneumonia (PCP) in which acute lung
      tissue destruction progressed within a few days to form multiple bullae in a
      patient with no HIV-1 infection. A 59-year-old man with mild pulmonary emphysema
      had been followed for two years. He had smoked 40 cigarettes per day for forty
      years. Six months before, bronchogenic carcinoma had been diagnosed in the lower
      right lung. After chemotherapy and radiotherapy, he had a sudden onset of high
      fever with respiratory failure. PCP was diagnosed by examination of the
      bronchoalveolar lavage fluid (BALF), and the patient was treated with
      intravenously administered trimethoprim-sulphamethoxazole (TMP-SMX) and
      methylprednisolone. His chest radiograph was not typical for PCP, and showed no
      diffuse ground-grass or fine granular opacities. A high-resolution CT of the
      chest revealed a low attenuation area consistent with severe emphysematous
      alterations and progressively enlarging bullae. A few cases have been reported of
      progressive pulmonary cystic disease associated with PCP pneumonia in patients
      with AIDS, in which the cause of bulla formation was thought to be lung
      parenchyma destruction induced by HIV itself, or increased elastase release from
      HIV-infected macrophages. The present case demonstrated that HIV infection was
      not an essential factor in the development of bullous changes. In a patient with
      a long history of smoking and emphysema, PCP may trigger-macrophage activation
      and an excessive release of leukocyte elastase, leading to elastin destruction in
      the alveoli.

PMID- 11579533
TI  - [Pulmonary alveolar proteinosis successfully treated by a modified lavage
      technique using high-frequency jet ventilation].
AB  - A 66-year-old woman presented with exertional dyspnea and productive cough. Chest
      radiography showed ground glass opacities and patchy infiltrates in both lungs.
      After confirmation of pulmonary alveolar proteinosis by bronchoalveolar lavage,
      she underwent conventional whole-lung lavage with slight improvement, with the
      aid of a partial extracorporeal circulation. After aggravation for one year, a
      modified lavage technique using high-frequency jet ventilation was used, and
      persistent improvement in oxygenation was achieved. We believe that this modified
      technique could be a useful method for pulmonary alveolar proteinosis.

PMID- 11579534
TI  - [A case of pulmonary lymphangioleiomyomatosis in an elderly woman].
AB  - We encountered a postmenopausal woman in whom pulmonary lymphangioleiomyomatosis
      was pathologically diagnosed. Cases of pulmonary lymphangioleiomyomatosis are
      rare in postmenopausal women. The patient was the oldest in whom such a case was
      reported in the literature. Pulmonary lymphangioleiomyomatosis should be on the
      list of differential diagnoses for cases of pulmonary cystic lesions, even in
      postmenopausal women.

PMID- 11579535
TI  - [A case of mediastinal adenocarcinoma of unknown origin presenting as a diffuse
      tumor shadow in the middle mediastinum].
AB  - We report a case of mediastinal adenocarcinoma of unknown origin presenting as a
      diffuse tumor shadow in the middle mediastinum. Cases of metastasis from cancer
      of unknown origin to hilar or mediastinal lymph nodes have often been reported.
      However, our case shows no round shadow indicating an enlarged lymph node,
      suggesting that the mediastinal adenocarcinoma originated from mediastinal
      tissue.

PMID- 11579536
TI  - [Visualization of biological phenomena by a multidisciplinary approach].

PMID- 11579537
TI  - [Time-resolved X-ray crystallography by Laue diffraction].

PMID- 11579538
TI  - [Single molecule manipulation and measurements with scanning probe microscopes].

PMID- 11579539
TI  - [Studying the operations of proteins using single molecule detection].

PMID- 11579540
TI  - [Method for protein preparation: recent development of ligation method for
      protein preparation].

PMID- 11579541
TI  - [Cell surface display: a novel expression system of proteins].

PMID- 11579542
TI  - [An opinion on where bioinformatics should proceed].

PMID- 11579543
TI  - [Genome analysis on the basis of protein structures].

PMID- 11579544
TI  - [Proteomic analysis using mass spectrometry].

PMID- 11579545
TI  - [Peptidome: the fact-database for endogenous peptides].

PMID- 11579546
TI  - [The large-scale exploration of protein complexes by proteomic analysis].

PMID- 11579547
TI  - [Cold-denatured state of beta-lactoglobulin].

PMID- 11579548
TI  - [Energy landscape obtained from molecular simulation].

PMID- 11579549
TI  - [Experimental studies on the folding dynamics of proteins].

PMID- 11579550
TI  - [Folding mechanism and folding rate].

PMID- 11579551
TI  - [Structural determinants of unfolding of 3-isopropylmalate dehydrogenase by means
      of the temperature-jump Laue method].

PMID- 11579552
TI  - [Understanding the mechanisms of self-assembly and sub A precision switch of the
      bacterial flagellum based on its molecular structure].

PMID- 11579554
TI  - [Evolution of molecules involved with neural transmission: in the case of
      catecholamine receptors and G protein alpha subunits].

PMID- 11579553
TI  - [Double-stranded RNA viruses--structure of huge transcription factories].

PMID- 11579555
TI  - [Molecular evolution of protein function].

PMID- 11579556
TI  - [Diversity of DNA recognition by transcription factors].

PMID- 11579557
TI  - [Structural bases of RNA polymerase functions].

PMID- 11579558
TI  - [Repair mechanism of oxidative DNA damages].

PMID- 11579559
TI  - [Structural biology of Holliday junction processing catalyzed by RuvABC
      resolvasome].

PMID- 11579560
TI  - [Structure and function of ribosome at atomic resolution].

PMID- 11579561
TI  - [tRNA mimicry in translational systems].

PMID- 11579562
TI  - [tRNA recognition and evolution of aminoacyl-tRNA synthetases].

PMID- 11579563
TI  - [Structure of the electron transfer complex between plant type ferredoxin and
      ferredoxin dependent assimilatory enzymes].

PMID- 11579564
TI  - [ATPase and ATP synthase].

PMID- 11579565
TI  - [AAA proteases].

PMID- 11579566
TI  - [Protease folding mediated by propeptides and protease inhibitors].

PMID- 11579567
TI  - [Physiological role of caspases].

PMID- 11579568
TI  - [Ubiquitin and proteasome].

PMID- 11579569
TI  - [Ubiquitin system connected with cell cycle control].

PMID- 11579570
TI  - [Molecular mechanism of bulk protein degradation in lysosome/vacuole].

PMID- 11579571
TI  - [Structural motifs in DNA cleaving enzymes].

PMID- 11579572
TI  - [Coordinated domain-domain interactions in the production of superoxide].

PMID- 11579573
TI  - [Structure-function relationship of metabotropic glutamate receptor].

PMID- 11579574
TI  - [Structure-function relationship of myosin].

PMID- 11579575
TI  - [Flagellar motor proteins].

PMID- 11579576
TI  - [ATP synthase (nano machine that produces ATP) and proton pumping ATPase].

PMID- 11579577
TI  - [Recent advance in studies of G protein-coupled receptors].

PMID- 11579578
TI  - [Muscular dystrophy and calpain].

PMID- 11579579
TI  - [Pathophysiological roles of two types of gingipains in periodontal diseases].

PMID- 11579580
TI  - [Relationship between prion diseases and conformational transition of peptides].

PMID- 11579581
TI  - [Alzheimer's disease and the proteins].

PMID- 11579582
TI  - [Molecular recognition by immunologically relevant receptors].

PMID- 11579583
TI  - [DNA diagnosis for eye diseases at the present time and in the future].

PMID- 11579584
TI  - [Histological study of the effect of conjunctival transplantation on rabbit
      cornea with alkali burned].
AB  - PURPOSE: A histopathological study to investigate the efficacy of conjunctival
      auto-transplantation on alkaline chemical burns of the ocular surface. MATERIAL
      AND METHODS: An alkaline chemical burn model was developed in one eye of rabbits
      using 0.1 N NaOH solution. In one group conjunctival transplantation was
      performed. A control group did not receive conjunctival transplantation. A
      histological follow-up study was performed by light microscopy with hematoxylin
      eosin stain and periodic acid Schiff staining by fluoro-microscopy using
      epithelial Keratin-AE 5 antibody, and by transmission electron microscopy(TEM).
      RESULTS: The transplanted group showed scar formation between the transplanted
      conjunctival tissue and the sclera. At 20 days and 8 weeks after the
      transplantation, neovascularization and cell infiltration in the subepithelium of
      the limbus was decreased compared with the transplanted group at 10 days. The
      control group showed a decrease of cell infiltration in the limbal area compared
      with the group at 10 days, but conjunctival tissue with thick collagenous tissue
      and neovascularization instead of scar tissue developed on the injured cornea. AE
      5 positive cells were not found in the limbus in either group. In the
      transplanted group, in TEM, the basement membrane of transplanted conjunctiva
      showed less irregularity, and degenerated fibroblasts were present at the margin
      of the scar tissue. In the control group, the basement membrane of the
      conjunctiva showed an irregular pattern and fibroblasts beneath the conjunctival
      epithelium had large nuclei. CONCLUSION: In the transplanted group, scar tissue
      developed and suppressed cell infiltration, neovascularization, and conjunctival
      tissue in the injured cornea and secured re-structuring of the limbal tissue.

PMID- 11579585
TI  - [A rabbit model for human cytomegalovirus retinitis].
AB  - PURPOSE: To develop a rabbit model for human cytomegalovirus(HCMV) retinitis.
      METHODS: 0.1 ml of 1 x 10(6) plaque forming units/ml HCMV was injected into the
      vitreous cavity of 10 pigmented rabbit eyes. The eyes were examined
      ophthalmoscopically on days 1, 2, 3, 4 and 7 and once a week thereafter until 4
      weeks after inoculation. Vitreal and retinal findings were graded from 0+ to 4+
      on a scale of increasing severity. In addition, we examined the enucleated eyes 3
      weeks after HCMV inoculation by histological and immunohistochemical techniques.
      RESULTS: All injected eyes developed vitreoretinal lesions. Vitreous opacities
      appeared the next day and increased until 4 days after HCMV inoculation. Whitish
      retinal exudates occurred on day 3 and increased until 3 weeks after HCMV
      inoculation. Vitreoretinal lesions then disappeared by 4 weeks after inoculation.
      Histological examination revealed intraretinal infiltration of inflammatory cells
      and disorganization of the inner retinal architecture. HCMV antigens were
      detected inside the retina by immunofluorescence using anti early protein
      antibody against HCMV. CONCLUSIONS: The results indicate that this rabbit model
      can be useful to develop and evaluate a new treatment modality for
      cytomegalovirus retinitis.

PMID- 11579586
TI  - [Endogenous substance P in corneal epithelial cells and keratocytes].
AB  - PURPOSE: To detect endogenous substance P(SP) and neurokinin receptor 1(NK1R) in
      cultured human epithelial cells of the cornea(HE) and human keratocytes(HK).
      METHOD: Messenger RNA(mRNA) expression of SP and endogenous SP in HE and HK were
      detected by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme
      linked immunosorbent assay (ELISA). mRNA expression of NK1R in HE and HK was
      detected by RT-PCR. RESULTS: The mRNA expression of SP and endogenous SP were
      recognized in HE and HK. The mRNA of NK1R was also expressed in HE and HK.
      CONCLUSION: It appears that endogenous SP regulates the biological functions of
      HE and HK in an autocrine or paracrine fashion.

PMID- 11579587
TI  - [DNA diagnosis of Leber's hereditary optic neuropathy performed at Keio
      University Hospital].
AB  - PURPOSE: To learn the clinical value of DNA diagnosis for Leber's hereditary
      optic neuropathy (LHON), we reviewed the results of DNA diagnosis performed at
      Keio University Hospital. METHODS AND PATIENTS: Included were 224 patients, 87
      patients at Keio University Hospital and 137 patients from other clinics, with
      bilateral optic neuropathy who were suspected of having LHON. With informed
      consent, the 3460, 9804, 11,778, 13,730, and 14,484 mutations of mitochondria DNA
      (mt-DNA) were examined form 1990 to 1998. Percentage of male patients, age at
      onset of the disease, and percentage of familial history were compared between
      patients with and without the mutations. The clinical diagnosis at the time of
      DNA analysis were examined in patients without the mutation. RESULTS: Seventy
      two(32%) of the 224 patients had one of the five mtDNA mutations, 63(88%)
      patients had the 11,778 mutation, 6(8%) had the 14,484 mutation, and 3(4%) had
      the 3460 mutation. In 72 patients with one of the LHON mutations, 89% of the
      patients were male, the average age of the disease onset was 24.3 years, and 42%
      of the patients had a familial history of the disease. Eighty (53%) of 152
      patients who did not have one of the 5 mutations were diagnosed as having
      bilateral optic atrophy with unknown causes. CONCLUSION: Although DNA diagnosis
      of LHON is a useful clinical test, we must know the clinical characteristics of
      the disease, before taking advantage of this analysis.

PMID- 11579588
TI  - [A new predictive formula for anterior chamber depth for pseudophakia].
AB  - PURPOSE: To develop a new predictive formula of the anterior chamber depth(ACD)
      of the pseudophakic eyes for more accurate intraocular lens(IOL) power
      calculation with the Ray Tracing method. METHODS: We studied a series of 149
      phacoemulsificated eyes with capsulorhexis and in-the-bag fixation of IOL. ACD
      was measured with a Jaeger type depth measuring unit which was attached to a slit
      lamp biomicroscope. We developed the formula with 3 variables: preoperative
      anterior corneal curvature with keratometer, and ACD and crystalline lens
      thickness with preoperative ultrasonography. We named the derived formula
      "formula H". We compared formula H with Olsen's predictive formula for the
      ACD(Olsen 92, Olsen 95). RESULTS: Mean absolute error between the predicted and
      postoperatively measured ACD was 0.174 +/- 0.133, 0.280 +/- 0.235, 0.229 +/-
      0.200 mm in formula H, Olsen 92, and Olsen 95, respectively. Formula H was
      significantly more accurate than both Olsen formulas(p < 0.001, p < 0.05,
      respectively). CONCLUSIONS: The accuracy of IOL power calculation can be improved
      with the new formula using the Ray Tracing method, using the new ACD predictve
      formula.

PMID- 11579589
TI  - [A new theoretical formula for the intraocular lens power calculation by the Ray
      Tracing Method].
AB  - PURPOSE: To study the mathematical properties of the intraocular lens(IOL) power
      calculation with the Ray Tracing method and to investigate its clinical results.
      METHODS: We first obtained a ray focusing equation with the Ray Tracing method,
      and then derived an emmetropizing equation and an equation for postoperative
      refraction. The exact calculation of these equations was investigated. A new IOL
      power calculation formula was consequently developed and named "formula H",
      combining it with the predictive formula for the postoperative anterior chamber
      depth of pseudophakic eyes in another report by us. A series of 150
      phacoemulsificated eyes with capsulorhexis and in-the-bag fixation of IOL were
      studied. The cases were divided into 3 groups; 16 short eyes(< 22 mm), 103 normal
      eyes(22 < or = and < 24.5 mm), and 31 long eyes(> or = 24.5 mm). The predictive
      error of formula H was compared with that of SRK-T, Holladay, and SRK II in each
      group. RESULTS: The exact calculation of emmetropizing power in taking account of
      a IOL design was mathematically impossible, or generally difficult. In the latter
      case, however, we could calculate it by solving a cubic or quartic equation.
      Exact and easy predictive calculation of postoperative refraction for any IOL
      design was possible if we knew such data as anterior and posterior curvature and
      thickness of each power of IOL. The mean absolute error of formula H was 0.38,
      0.34, 0.36, 0.44 diopter, in all eyes, short eyes, normal eyes, and long eyes,
      respectively. Formula H was significantly more accurate than all other formulas
      in all eyes, in short eyes and normal eyes. CONCLUSIONS: For clinical use,
      predictive calculation of postoperative refraction should be recommended but
      calculation of emmetropizing power should be abandoned. But emmetropizing
      calculation is useful and important for the fundamental study of IOL power
      calculation. Formula H was more accurate than all other formulas and very useful
      for clinical use.

PMID- 11579591
TI  - [Bilateral progressive supra-fixing eyes with congenital misinsertion of inferior
      rectus muscles--a case report].
AB  - BACKGROUND: We report on a rare case with misinsertion of the inferior rectus
      muscles, that showed bilateral progressive supra-fixing eyes. CASE: A 68-year-old
      woman showed bilateral progressive supra-fixing eyes with low vision that was
      caused by microcorneas and retionochoroidal atrophy. Passive infraduction was
      restricted bilaterally, but the right inferior rectus muscle was innervated
      normally. Magnytic resonance imaging(MRI) demonstrated nasal misposition of
      bilateral inferior rectus muscles. The patient's eye position was improved after
      combined transposition of the inferior rectus muscles that were misinserted
      nasally to the inferior poles of the eyes and superior rectus muscle recession,
      without any complications. CONCLUSION: A dysfunction of bilateral depressor
      muscles and low vision may cause this condition. Accurate diagnosis with MRI and
      correction of the affected muscles to the normal anatomical position produces
      satisfying results in such cases.

PMID- 11579590
TI  - [Characteristics of hyperacuity sensitivity in normal and cyclovertical deviated
      subjects].
AB  - PURPOSE: To compare the sensitivity of hyperacuity of cyclovertical deviated
      patients with that of normal subjects. SUBJECTS AND METHODS: The sensitivity of
      hyperacuity was measured in 42 normal and 12 cyclovertical deviated patients,
      using a newly developed computerized device which randomly presents two targets
      opposed vertically or horizontally on a cathode ray tube(CRT) display. RESULTS:
      In normal subjects, lower thresholds were obtained when the targets were aligned
      either vertically or horizontally. These highly sensitive ranges were defined as
      "the neutral zone of hyperacuity". An anisotropy of the sensitivity of
      hyperacuity was observed. i.e., better thresholds were obtained when the offset
      was set away from the neutral zone, whereas worse thresholds were obtained when
      the offset as close to the neutral zones. In cyclovertical deviated patients, the
      thresholds of hyperacuity were high around the neutral zones, which may indicate
      dysfunction of the central nervous system. CONCLUSION: This analytical method may
      be useful to investigate the pathophysiology of the patients with cyclovertical
      deviations.

PMID- 11579592
TI  - [Prognostic factors of renal pelvic and ureteral cancer: a multivariate
      analysis].
AB  - We clinicopathologically reviewed 54 cases (40 males and 14 females) of renal
      pelvic and ureteral cancer examined between 1983 and 1998, in order to determine
      the impact of prognostic factors. Follow-up ranged from 2 to 173 months (mean,
      45.6 months). The age of the patients ranged from 39 to 88 years (mean, 68.9
      years). The 1, 3 and 5-year cause-specific survival rates (Kaplan-Meier's method)
      for all of the patients were 74.6%, 58.4% and 54.5%, respectively. According to
      univariate analysis, a high grade and high stage of tumor, the presence of
      lymphatic invasion and positive regional lymph nodes indicated a significantly
      poor prognosis. On the other hand, multivariate analysis using Cox proportional
      hazards regression revealed the presence of lymphatic invasion as the most
      significant predictor of survival. Therefore, patients with lymphatic invasion
      have a poor prognosis, and the development of effective adjuvant therapy is
      needed to improve the outcome in these patients.

PMID- 11579593
TI  - Angiogenin expression in superficial bladder cancer.
AB  - The concentration of angiogenin in the tumor tissues and corresponding normal
      tissues of 20 superficial bladder cancer patients was measured using a sandwich
      enzyme immunoassay (ELISA). In addition, immunohistochemical assays were
      performed in order to clarify the localization of angiogenin expression in
      bladder tissue. The mean concentration of angiogenin in the carcinoma tissues was
      significantly lower than that in the corresponding normal tissues (P < 0.001).
      Angiogenin expression was weak in the bladder cancer cells. The present results
      show that the expression of angiogenin is lower in superficial bladder cancer
      tissues than in corresponding normal tissues. The biological role of angiogenin
      in carcinogenesis of bladder cancer may be different from those of other
      angiogenic factors.

PMID- 11579594
TI  - [Intermittent androgen deprivation treatment of prostate cancer restarted at low
      level of serum prostate specific antigen: a pilot study].
AB  - We report a pilot study on a novel protocol of intermittent androgen deprivation
      (IAD) treatment of prostate cancer (PC), in which androgen deprivation is
      restarted when serum prostatic specific antigen (PSA) level reached more than 2
      ng/ml and is stopped when PSA level decreased below 0.3 ng/ml. Thirty-two
      patients (aged 60 to 86 years, median 74 years) with prostate cancer (Stage A in
      4 patients, B in 20, C in 1, D in 5, and relapse after radical prostatectomy in
      2) were treated with IAD. Median serum PSA prior to the start of endocrine
      therapy was 15.65 (range 2.67 to 306.3) ng/ml. Eleven patients were treated with
      lutenizing-hormone-releasing hormone (LHRH) agonist alone and 21 were treated
      with LHRH agonist plus an antiandrogen. Median duration of first endocrine
      therapy was 572 (range 100 to 1,543) days. Median serum PSA at the start of first
      off-phase was 0.038 (range 0.003 to 0.489) ng/ml. After a median of 207 days
      (range 140 to 843) of follow-up, 19 patients were in the first cycle, 9 in the
      second cycle, 3 in the third cycle, 1 in the fourth cycle. Two patients developed
      androgen-independent PC. The median duration of first off-phase of IAD was 287
      days. There was a significant inverse relation between the duration of the first
      on-phase and testosterone level measured 4 months after the cessation of first on
      phase therapy (R = -0.518). These results suggest that our protocol provides a
      reasonable length of off-phase duration and that the long term-androgen
      deprivation phase might delay the recovery of the testicular endocrine function
      which should be maintained during the off-phase of IAD.

PMID- 11579595
TI  - [Retropubic radical prostatectomy with the use of ultrasonic cutting and
      coagulating system (AutoSonix System)].
AB  - We report our experience of using the ultrasonic coagulating and cutting device,
      AutoSonix System, which began in January 2000 to reduce the amount of bleeding in
      radical retropubic prostatectomy. The mean age of the 24 prostate cancer patients
      operated on was 68.2 years old. The operation results were excellent; the mean
      operation time was 227 +/- 29 minutes (mean +/- standard deviation), and the mean
      amount of blood loss during the operation was 215 +/- 114 ml. There were no major
      complications. After three months or more of follow-up, no patients needed any
      pads for urinary incontinence. Only one case showed a stricture at cystourethral
      anastomosis. AutoSonix System was useful to reduce the blood loss from the venous
      plexus in the pelvic cavity. We believe that radical prostatectomy would be safer
      if this device would be used by the urologist.

PMID- 11579596
TI  - [Giant cystic pheochromocytoma: a case report].
AB  - The patient, a 59-year-old woman, was referred to our University Hospital for
      evaluation of a left mass. Ultrasonography revealed a left adrenal cystic mass.
      On excretory urograms, the left kidney was pressed downward by a suprarenal mass,
      and computerized tomography (CT) and magnetic resonance imaging (MRI) confirmed
      an adrenal cyst. 131I-meta-iodo-benzylguanidine (MIBG) scintigraphy showed
      prominent accumulation in the left adrenal mass and the capsule. Considering the
      elevation of catecholamines in both blood and urine samples, we performed a left
      adrenalectomy with a presumptive diagnosis of pheochromocytoma (tumor size: 11.6
      x 7.5 x 6.5 cm, tumor weight 720 g). The subsequent pathological examination
      confirmed a left giant cystic pheochromocytoma. 131I-MIBG scintigraphy was the
      most useful tool in the diagnosis of the cystic pheochromocytoma.

PMID- 11579597
TI  - [Partial nephrectomy using a microwave tissue coagulator for bilateral renal cell
      carcinomas: a case report].
AB  - We report a case of bilateral renal cell carcinomas in a 56-year-old male treated
      by partial nephrectomy at the same time using a microwave tissue coagulator
      technique. The patient did not need dialysis after the operation because we did
      not need to sacrifice the artery feeding to normal renal tissue during the
      operation. This technique has advantages of nephron sparing without occlusion of
      the renal artery, and decreased operation time and blood loss.

PMID- 11579598
TI  - [A case of renal pelvic tumor with heterotopic bone formation].
AB  - The patient was a 74-year-old man who was referred to our hospital with a
      complaint of left flank pain. Laboratory data were almost within normal limits
      and urine cytology was positive. X-ray examination revealed a calcification in
      the left kidney and abdominal CT scan confirmed the presence of a heterogenous
      renal pelvic mass which contained a calcification. Based on these examinations, a
      diagnosis of a renal pelvic cancer with heterotopic bone formation was made.
      Subsequently, left nephroureterectomy was performed. Grossly, the renal pelvis of
      the resected kidney was filled with a mass which had a white cut surface and bone
      like tendency. Histopathologically, a poorly differentiated transitional cell
      carcinoma with massive bone formation was found. Fifty five cases of heterotopic
      bone formation in the kidney have been reported in Japan. Among the cases, 4
      cases were complicated with renal pelvic tumor and our case was the second case
      of heterotopic bone formation complicated with a transitional cell carcinoma of
      the renal pelvis in Japan.

PMID- 11579599
TI  - Ureteral endometriosis: a case report and a review of the Japanese literature.
AB  - A 42-year-old woman was referred to our hospital because of abdominal fullness
      and a large abdominal mass. Computed tomography (CT) demonstrated bilateral
      ovarian tumors, uterine myoma and left hydronephrosis. On excretory urography the
      left kidney was not visualized and retrograde pyelography (RP) revealed left
      hydronephrosis and a filling defect in the left lower ureter. Based on the
      diagnoses of endometriosis of bilateral ovaries, uterine myoma and a left
      ureteral tumor, abdominal total hysterectomy, right salpingo-oophorectomy and
      partial ureterectomy were performed. Pathologically, in the uterus, both
      leiomyoma and adenomyosis, and endometriosis of the right ovary and ureter were
      diagnosed. Medication with buserelin acetate was started.

PMID- 11579600
TI  - Ureteral fibroepithelial polyp associated with urolithiasis induced by steroid
      therapy in a child: a case report.
AB  - A 14-year-old boy complained of left flank pain. He had been given high-dose
      corticosteroid therapy for chronic inflammatory demyelinating polyneuropathy
      (CIDP). Retrograde pyelography revealed irregular defects at the left
      ureteropelvic junction (UPJ), and ureteroscopy demonstrated ureteral polyp. The
      polyp was removed and histologically diagnosed as fibroepithelial polyp.
      Hypercalciuria due to the corticosteroids and bedridden was assumed to have been
      a causative factor in the stone formation. To our knowledge, this is the first
      report of a ureteral fibroepithelial polyp in children associated with
      urolithiasis, and associated with CIDP.

PMID- 11579601
TI  - [A case of transitional cell carcinoma of the urinary bladder with high serum
      level of CEA and CA19-9].
AB  - An 85-year-old male with asymptomatic gross hematuria was diagnosed with invasive
      bladder tumor, transitional cell carcinoma grade 3. Serum levels of CEA and CA19
      9 were elevated and histological examination revealed expression of both markers
      in the cytoplasm of cancer cells. Out of therapeutic options, intra-arterial
      chemotherapy and radiotherapy were selected because of his age. During the
      treatment, serum levels of CEA and CA19-9 decreased along with reduction of tumor
      size. These serum markers have been reported to be elevated in 10 to 60% of
      patients with bladder tumor and are useful markers for evaluation of the
      treatment as suggested in the present case.

PMID- 11579602
TI  - [A case of urachal xanthogranuloma causing recurrent intestinal obstruction].
AB  - A 68-year-old male was admitted to our hospital with the chief complaints of
      lower abdominal pain and fever. There was a tender mass palpable in the lower
      abdomen. Plain abdominal X-ray film revealed multiple air-fluid levels with
      dilated small bowel loops, suggesting intestinal obstruction. Abdominal
      ultrasonography, computed tomography and magnetic resonance imaging revealed a
      solid mass extending from umbilicus to the bladder dome beneath the rectal
      muscle. There was normal mucosa of the bladder by cystoscopic examination. A
      urachal tumor was clinically suspected and en bloc removal of the mass, the
      remaining urachus, umbilicus, omentum and bladder dome was performed. The
      histological diagnosis was urachal xanthogranuloma. The patient has remained in
      good health without any recurrence for 6 months since the surgery. We discuss
      urachal xanthogranuloma in the literature.

PMID- 11579603
TI  - [Progression from adenocarcinoma to small cell carcinoma of the prostate during
      endocrinotherapy: a case report].
AB  - A 72-year-old man had undergone surgical castration for metastatic prostate
      cancer (stage D2, the PSA value was 4,300 ng/ml) in September, 1997. He was well
      clinically for 16 months with undetected level of PSA. However, he presented with
      general malaise and gross hematuria in May, 1999. After admission to our hospital
      his condition rapidly deteriorated and he died one week later with respiratory
      failure. Autopsy revealed extensive involvement of the prostate and bladder by
      solid tumor with multiple metastases in lungs, liver, spleen, kidneys and bone.
      Histological examination revealed pure small cell carcinoma of the prostate.

PMID- 11579604
TI  - [Two cases of giant female urethral stone in long-term bedridden elderly].
AB  - A 78-year-old female suffering from a cerebral infarction and subdural hematoma
      was referred to us due to a hard mass in the anterior vaginal wall which was
      disclosed during gynecological examination. An abdominal X-ray, computed
      tomography (CT) and magnetic resonance imaging (MRI) showed that a large spindle
      shaped stone, 60 x 42 mm in size, was impacting the urethra. It was impossible to
      catheterize the urethra. The stone gradually projected through the external
      urethral meatus and was removed by grasping and drawing with forceps. Another 83
      year-old female with senile dementia was referred to us because of
      macrohematuria. An abdominal X-ray and CT showed the presence of two oval bladder
      stones, 32 x 24 mm and 30 x 21 mm in size. During a follow-up, one of the stones
      projected partially through the external urethral meatus and was removed by
      drawing with forceps. After a week, the other stone impacted the urethra and was
      removed in the same way. Both women were frail, bedridden institutionalized
      elderly with severe dementia, and their urination had been managed with diapers
      for years. As the proportion of elderly people in Japan rapidly increases, female
      urethral stones migrating from the urinary bladder, once very rare, may increase
      in number, to which we must pay attention.

PMID- 11579605
TI  - [A giant testicular tumor detected with dyspnea due to lung metastases: a case
      report].
AB  - A 19-year-old male presented with dyspnea. Clinical examination revealed the left
      infant-head-sized testicular tumor, multiple lung metastases and retroperitoneal
      bulky lymph node metastasis with marked elevation of serum lactic dehydrogenase
      (LDH) and alpha-fetoprotein. Left radical orchiectomy followed by the
      chemotherapy with etoposide and cisplatin (EP) for 4 cycles was performed. The
      tumor weighed 1,700 g, and was pathologically diagnosed as mixed germ cell tumor
      consisting of embryonal carcinoma and yolk sac tumor. After the treatment, the
      tumor markers were normalized with partial response (PR) of lung metastases and
      complete response (CR) of retroperitoneal lymph node metastasis. Thereafter,
      biopsy of lung metastases through video-assisted thoracoscopic surgery (VATS) was
      performed, and pathologically no viable cells were detected. Five months after
      the treatment, he was seized with convulsion due to brain metastasis with
      hemorrhage. Therefore, a surgical resection of brain metastasis and 2nd line
      chemotherapy with etoposide, ifosfamide and cisplatin (VIP) chemotherapy for 3
      cycles was performed. The patient has been free of recurrence for 21 months after
      the 2nd line chemotherapy.

PMID- 11579606
TI  - [Testicular malignant lymphoma: report of two cases].
AB  - One patient was a 79-year-old man, who exhibited right scrotal swelling and the
      other patient was a 73-year-old man, who exhibited left scrotal swelling. Both
      patients received high orchiectomy under the diagnosis of testicular tumor and
      the histopathological diagnosis in both patients was non-Hodgkin's lymphoma. Case
      1 was diffuse, medium-sized B cell type, and case 2 was diffuse, mixed B cell
      type. Several examinations revealed no apparent additional involvement. Neither
      patient received any adjuvant chemotherapy nor postoperative irradiation. In case
      1, for a period of 4 years following high orchiectomy, the patient has been doing
      well. In case 2, 2 years and 6 months postoperatively, para-aortic lymph node
      swelling occurred, and chemotherapy was initiated with THP-COP but the patient
      died at 3 years and 3 months after high orchiectomy.

PMID- 11579607
TI  - Comparison of the APACHE II and APACHE III scoring systems in patients with
      respiratory failure in a medical intensive care unit.
AB  - BACKGROUND AND PURPOSE: This retrospective study compared the capability of the
      Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scoring
      systems to predict outcome and determined the independent predictors of survival
      in these scoring systems for patients with respiratory failure in a medical
      intensive care unit (ICU). MATERIALS AND METHODS: Seven hundred and eight
      patients with respiratory failure admitted to the medical ICU throughout a 9-year
      period were studied. Patients with an ICU stay of less than 24 hours, patients
      under 12 years of age, and burn and surgery patients were excluded. APACHE scores
      were calculated at 24 hours after admission. Student's t-test was used to compare
      the total APACHE scores of survivor and non-survivor groups. Multivariate
      logistic regression analysis was used to determine which variables were
      predictors of mortality. The discriminative power of APACHE scores to predict in
      hospital mortality was studied by the area under the receiver operating
      characteristic curves of the APACHE II and APACHE III systems, respectively.
      RESULTS: Both systems showed a significant association between higher scores and
      higher mortality. The APACHE II system under-predicted the actual hospital
      mortality rate. The APACHE III systems had a higher discriminative power (area
      0.7462) than the APACHE II systems (area 0.6856; p < 0.05). The independent
      predictors of survival as assessed by APACHE II and III systems were respiratory
      rate, arterial oxygen pressure, oxygen gradient between alveoli and artery, serum
      creatinine concentration, and the presence of neurologic abnormalities.
      CONCLUSIONS: The APACHE III systems has greater discriminative power than the
      APACHE II systems for predicting in-hospital mortality. The variables of
      oxygenation, mean artery pressure, respiratory rate, serum creatinine
      concentration, and Glasgow Coma Scale play important roles in predicting survival
      for patients with respiratory failure.

PMID- 11579608
TI  - Clinicopathologic and prognostic differences between patients with hepatitis B-
      and C-related resectable hepatocellular carcinoma.
AB  - BACKGROUND AND PURPOSE: Hepatitis B and C viral infections are important factors
      in the development of hepatocellular carcinoma (HCC). This study examined the
      clinicopathologic and prognostic differences in patients with hepatitis B- and C
      related resectable HCC. METHODS: A total of 270 HCC patients who underwent
      hepatic resection were enrolled. Among these patients, 211 were positive for
      hepatitis B surface antigen (HBsAg) and 59 were positive for anti-hepatitis C
      virus antibody (anti-HCV). The clinical manifestations, pathologic features, and
      treatment outcomes were compared between the HBsAg-positive and anti-HCV-positive
      groups. RESULTS: Compared to anti-HCV-positive patients, HBsAg-positive patients
      were significantly younger, had a higher familial incidence of HCC, larger tumor
      size, and a higher incidence of multiple tumors. HCC patients who were anti-HCV
      positive had worse liver function and a higher incidence of history of blood
      transfusion. DNA flow cytometric analysis revealed significantly more
      proliferative activity in the non-tumor part of the liver in HBsAg-positive HCC
      patients. The 1-, 3-, and 5-year overall survival rates of HBsAg-positive
      patients were 79%, 57%, and 48%, respectively, and for anti-HCV-positive patients
      were 91%, 75%, and 62%, respectively. HBsAg-positive patients had a significantly
      lower overall survival rate than anti-HCV-positive patients (p = 0.018).
      CONCLUSIONS: HBsAg-positive patients with resectable HCC had a less favorable
      survival rate after tumor resection than anti-HCV-positive HCC patients. This
      survival difference might have been related to the relatively advanced stage of
      disease and the higher proliferative activity of the non-tumor part of the liver
      in HBsAg-positive HCC patients.

PMID- 11579609
TI  - Clinicopathologic study of Kaposi's sarcoma and strain analysis of human
      herpesvirus 8 (HHV-8) DNA in the Hua-Lien area of eastern Taiwan.
AB  - BACKGROUND AND PURPOSE: Kaposi's sarcoma (KS) is a spindle cell malignancy of
      endothelial cell origin. The tumor has been demonstrated to be associated with
      human herpesvirus 8 (HHV-8) or Kaposi's sarcoma-associated herpesvirus-like virus
      (KSHV). Previous studies have revealed the distribution of unique viral strains
      in different ethnic populations. Eastern Taiwan has an ethnically mixed
      population with a relatively high incidence of KS. This study was designed to
      characterize the clinicopathologic features of KS and to evaluate the HHV-8
      strain distribution in the Hua-Lien area of Eastern Taiwan. METHODS: Clinical
      records and laboratory data were collected from 15 cases of KS diagnosed and
      treated between 1993 and 1999 in Tzu-Chi General Hospital. For nine cases,
      paraffin blocks were available for the molecular study of HHV-8. HHV-8 genomic
      variation was analyzed using polymerase chain reaction nucleotide sequencing of
      ORF26 and ORF75 of HHV-8 genomes derived from different subgroups of KS. RESULTS:
      Among the 15 patients with KS, two had AIDS-associated disease, four had gouty
      arthritis and psoriasis and were receiving corticosteroid therapy (iatrogenic
      type), and nine had classical KS. Nine of the 15 cases occurred in aborigines,
      including one with AIDS-associated disease, four with iatrogenic disease, and
      four with classical disease. Among the nine cases for which tissue was available
      for DNA analysis, eight were positive for HHV-8 DNA. Sequence analysis revealed
      that the C strain occurred in three Han Chinese KS patients, whereas a hitherto
      rarely described strain (strain D) occurred in all four aborigines tested
      (including one with AIDS-associated KS) and one Han Chinese with AIDS from Burma.
      CONCLUSION: This study found a high proportion of iatrogenic KS and the finding
      of a rarely described strain D virus in Eastern Taiwan aborigines. Our studies
      further confirm the distribution of different types of KS and virus strains in
      different ethnic populations.

PMID- 11579610
TI  - Psychometric assessment of the Chinese language version of the St. George's
      Respiratory Questionnaire in Taiwanese patients with bronchial asthma.
AB  - BACKGROUND AND PURPOSE: The St. George's Respiratory Questionnaire (SGRQ) is a
      disease-specific quality-of-life instrument. It was designed to measure quality
      of life in obstructive pulmonary disease, and its reliability and validity have
      been demonstrated in different language versions. The purpose of this study was
      to determine the psychometric properties of a Chinese language version of the
      SGRQ in Taiwanese asthma patients. METHODS: A convenient sample of 124 asthma
      patients were recruited from the outpatient asthma clinic of a teaching hospital
      in the Taipei area. The inclusion criteria were outpatient, coherent, and a
      clinical diagnosis of asthma. Patients with additional medical conditions
      considered to impact the quality of life were excluded. Three component scores
      (symptoms, activity, and impacts) and a total score were calculated to assess the
      SGRQ's psychometric characteristics. Data including demographic characteristics,
      history of emergency visits and hospital admissions, asthma severity, and quality
      of life were collected by questionnaires. Cronbach's formula for the alpha
      coefficient was used to estimate the internal consistency and reliability of the
      SGRQ. Pearson's product-moment correlation was used to estimate the concurrent
      validity of the SGRQ. The discriminating validity of the SGRQ was determined by
      the t-test for independent samples. RESULTS: Results showed that the SGRQ was
      internally consistent, and had good content and face validity. The SGRQ total
      score was significantly correlated with both the Health Index and the RAND 36
      item Health Survey (p < 0.05). The SGRQ discriminated patients with respect to
      asthma severity (p < 0.001), history of prior emergency visits (p < 0.05), and
      history of prior hospital admissions (p < 0.05). CONCLUSIONS: This study
      demonstrated that the Chinese language version of the SGRQ has internal
      consistency and validity with strong evidence of content, concurrent, and
      discriminating validity in Taiwanese asthma patients. These findings suggest that
      it is a useful measure of quality of life in Taiwanese asthma patients.

PMID- 11579611
TI  - Postoperative 6-month and 1-year evaluation of health-related quality of life in
      total hip replacement patients.
AB  - BACKGROUND AND PURPOSE: During the last decade, health-related quality of life
      (HRQOL) has been recognized as a principal outcome measure for total hip
      replacement (THR). However, most THR outcome studies in Taiwan have limited their
      assessments to the areas of pain relief and physical function. This study
      examined the effects of THR on quality of life. METHODS: A longitudinal
      prospective study design was adopted. A total of 76 THR patients were enrolled.
      Disease specific (Harris Hip Score) and generic measures (SF-36) were determined
      before and after surgery. Postoperative evaluations were completed at 6 months
      and 1 year. Patient characteristics and related medical information were derived
      from chart data. RESULTS: Significant improvement was found in HRQOL. This
      improvement was maintained at both 6-month and 1-year follow-up. Specifically,
      the mean Harris Hip Score improved from 44.7 to 88.9 at the 6-month postoperative
      evaluation, and further improved to 91.3 at the 1-year evaluation. In the SF-36,
      each domain of health status showed a significant improvement at 6-month and 1
      year evaluations (p < 0.05 or p < 0.01). CONCLUSIONS: The results of the Harris
      Hip Score and the SF-36 showed that THR not only relieved physical pain but also
      enhanced all aspects of quality of life. In addition to pain relief and improved
      physical function, improvements in role limitations due to physical or emotional
      problems were also significant. These findings indicate that a general health
      survey should be combined with a disease-specific scoring system to assess THR
      outcome.

PMID- 11579612
TI  - Effectiveness of postoperative adjuvant therapy in improving reproductive outcome
      of endometriosis-associated infertility.
AB  - BACKGROUND AND PURPOSE: Treatment of endometriosis-associated infertility has not
      yet become standardized. Various protocols including surgical treatment, medical
      therapy, and a combination of both have been suggested but their use remains
      controversial. The objective of the present study was to determine whether
      postoperative adjuvant therapy for endometriosis is effective in improving
      reproductive outcome. METHODS: Medical records of infertile patients with newly
      diagnosed endometriosis treated in a university teaching hospital during a 50
      month period were reviewed. After exclusion of patients with other major
      infertility factors, a total of 209 patients were included in the retrospective
      analysis. These patients were divided into those receiving (n = 78) or not
      receiving (n = 131) peri- or postoperative adjuvant medical therapy. The adjuvant
      therapies included danazol (n = 62), gonadotropin releasing hormone analogues (n
      = 11), progestins (n = 3), oral contraceptives (n = 1), and mixed treatment (n =
      1). RESULTS: The pregnancy rate was lower in those receiving adjuvant therapy,
      although this result was not significant (32.1% vs 45.8%; p = 0.05). When
      patients using postoperative danazol therapy were considered alone, the pregnancy
      rate in patients receiving adjuvant therapy was significantly lower than that in
      patients not receiving it (p = 0.047). When the stage of endometriosis was
      considered, the pregnancy rate in patients receiving adjuvant therapy was again
      lower than in those not receiving it in patients with minimal or mild
      endometriosis (42.9% vs 60%; p = 0.043). However, in patients with moderate or
      severe endometriosis, the pregnancy rate was not different in the two groups (31%
      vs 36%; p = 0.56). Postoperative assisted reproductive techniques (ART) including
      controlled ovarian hyperstimulation/intrauterine insemination (COH/IUI) and in
      vitro fertilization (IVF) were effective in improving the pregnancy rates for all
      patients (53.9% with ART vs 33.1% without; p = 0.003) and for patients with
      advanced endometriosis (47.7% with ART vs 27.2% without; p = 0.016). CONCLUSIONS:
      Our results suggest that postoperative adjuvant therapy is ineffective in
      improving reproductive outcome in patients with either early (minimal or mild) or
      advanced (moderate and severe) endometriosis. This finding suggests that if
      fertility is the goal of treatment, adjuvant therapy may be unnecessary after
      surgery. In contrast, our data suggest that empirical ART, including COH/IUI or
      IVF, may be a better alternative to improve the pregnancy outcome after surgery.

PMID- 11579613
TI  - Expression of transforming growth factor-alpha in adenoid cystic carcinoma of the
      salivary gland.
AB  - BACKGROUND: Transforming growth factor-alpha (TGF-alpha) is expressed in both
      normal and malignant epithelial cells. Although the expression of TGF-alpha has
      been extensively studied in some human epithelial neoplasms, its expression in
      adenoid cystic carcinomas (ACCs) of the salivary gland has not been reported.
      METHODS: This study used an immunohistochemical technique to assess the
      expression of TGF-alpha in 40 ACC specimens from the salivary glands, seven
      specimens from labial minor salivary glands adjacent to mucoceles, and five
      specimens from normal submandibular glands. RESULTS: In the normal submandibular
      gland specimens, positive TGF-alpha staining was found in all ductal segments as
      well as in serous and some mucous acinar cells. In labial minor salivary glands
      adjacent to mucoceles, positive TGF-alpha staining was found in ductal, serous
      acinar, serous demilune, and a few mucous acinar cells. Positive TGF-alpha
      immunostaining was observed in all five salivary gland ACC specimens with a solid
      histologic pattern, and 31 of the 35 salivary gland ACC specimens with a tubulo
      cribriform histologic pattern. Overall, 36 of 40 ACCs of the salivary gland
      expressed TGF-alpha. Positive TGF-alpha staining was found in the salivary gland
      ACC specimens with solid, tubular, duct-like, and pseudocystic structures. No
      significant correlation was found between TGF-alpha expression in ACCs of the
      salivary gland and age, sex, primary cancer location, TNM status, clinical stage,
      prognosis, histologic type, perivascular or perineural invasion, focal necrosis
      of the tumor, or cellular atypia. CONCLUSIONS: This study demonstrated that
      ductal and acinar cells of the normal submandibular gland and of labial minor
      salivary glands adjacent to mucoceles are the major sites of TGF-alpha synthesis
      and secretion. Furthermore, TGF-alpha is biosynthesized in salivary gland ACC
      tumor cells, forming solid, tubular, duct-like, and pseudocystic structures. Our
      data suggest that TGF-alpha may play an important biologic role as a mitogen in
      the growth of salivary gland ACC.

PMID- 11579614
TI  - Association of pityriasis rosea with human herpesvirus-6 and human herpesvirus-7
      in Taipei.
AB  - BACKGROUND AND PURPOSE: Pityriasis rosea (PR) is a common papulosquamous skin
      disease with unknown etiology. The possible relationship of PR with human
      herpesvirus infection (HHV) has been extensively studied. This study used the
      polymerase chain reaction (PCR) to investigate the presence of human herpesvirus
      6 and 7 (HHV-6 and HHV-7) in 41 PR patients from two hospitals in Northern
      Taiwan. The epidemiologic features of PR in patients were also studied. METHODS:
      A total of 41 PR patients (11 males, 30 females) were enrolled in this study from
      April 1999 to March 2000. PCR of skin biopsy specimens from 24 PR patients was
      used to identify the existence of HHV-6 and HHV-7. Viral culture from PR biopsy
      specimens was also performed. Blood from these patients was sampled for Venereal
      Disease Research Laboratory tests. Skin biopsies from 20 age- and sex-matched
      controls with other skin diseases were also subjected to PCR study. RESULTS: The
      ages of the 41 PR patients ranged from 8 to 62 years. An increased incidence
      (17/41) of PR episodes was observed during the spring. Both HHV-6 and HHV-7 DNA
      was below the limit of detection in all biopsy specimens from patients and
      healthy controls. Viral culture for HHV was negative in all patients. CONCLUSION:
      The epidemiologic features of PR in this series are comparable to other studies
      except for an exaggerated female predominance (male:female ratio 1:2.7). Our data
      indicate a lack of association between HHV-6 and HHV-7 infection and PR.

PMID- 11579615
TI  - Lipid myopathy associated with renal tubular acidosis and spastic diplegia in two
      brothers.
AB  - Lipid myopathy is a group of disorders involving mitochondrial fatty acid
      oxidation. We describe two brothers, 3 years 8 months old and 2 years 9 months
      old, respectively, with progressive spastic diplegia, developmental delay,
      failure to thrive, and chronic metabolic acidosis who had lipid myopathy and
      renal tubular acidosis. Brain magnetic resonance imaging revealed demyelinating
      changes in the periventricular white matter, which was compatible with spastic
      diplegia. These symptoms may be related to errors in fatty acid metabolism.
      Cerebral palsy had been misdiagnosed in both of these patients at another
      hospital. Therefore, for patients with late-onset and progressive spastic
      diplegia, detailed investigations for underlying diseases are warranted.

PMID- 11579616
TI  - Renal oncocytoma in acquired renal cystic disease.
AB  - Renal oncocytoma is a rare benign tumor of the kidney that accounts for about 5%
      of renal tumors. Acquired renal cystic disease (ARCD) is commonly seen in
      dialyzed patients. However, the occurrence of renal oncocytoma in ARCD has rarely
      been reported. We report such a case in a 67-year-old man who had hypertension
      associated end-stage renal disease and had received regular hemodialysis for 5
      years. Radiologic diagnostic studies demonstrated a renal mass in the left
      atrophic cystic kidney that increased in size from 2 cm to 4 cm during 2 years of
      follow-up. Under the diagnosis of renal cell carcinoma, he received left radical
      nephrectomy. The pathologic examination revealed renal oncocytoma with a well
      cirumscribed, homogenous, mahogany-brown tumor on a background of ARCD. Although
      patients with ARCD have a higher incidence of renal malignancies, renal
      oncocytoma may occur in these patients and may be managed conservatively.

PMID- 11579617
TI  - Diabetic ketoacidosis and hypogonadotropic hypogonadism in association with
      transfusional hemochromatosis in a man with beta-thalassemia major.
AB  - We report a 23-year-old man with beta-thalassemia major and transfusional
      hemochromatosis, which manifested as diabetic ketoacidosis and hypogonadotropic
      hypogonadism. This unusual presentation of diabetic ketoacidosis in
      hemochromatosis has rarely been reported. Magnetic resonance imaging of the
      abdomen showed decreased signal intensity in the liver, spleen, and pancreas. In
      addition, the pituitary gland also showed heterogeneous low signal intensity,
      compatible with hemochromatosis. He was treated with insulin supplements and
      pulsatile human chorionic gonadotropin administration. Clinical improvement was
      noted after hormone replacement. Intensive iron chelation therapy was given to
      prevent cardiac complications, and to restore his gonadal function. During follow
      up, the patient experienced improvement in libido and sexual potency.

PMID- 11579618
TI  - Management of multiple level spondylolysis of the lumbar spine in young males: a
      report of six cases.
AB  - The most common procedure for surgical treatment of lumbar spondylolysis is
      intertransverse processes spinal arthrodesis with instrumentation. However, this
      procedure is associated with significant morbidity on long-term follow up. Direct
      repair of spondylolysis is an alternative method for preservation of motion
      segment and anatomic continuity in young adults with multiple level
      spondylolysis. From 1992 through 1998, six soldiers with a diagnosis of multiple
      level spondylolysis who complained of persistent low back pain were treated in
      our hospital. Spondylolysis involved two levels in five cases and three levels in
      one case. All patients underwent serial roentgenography of the lumbar spine and a
      staged pars interarticularis infiltration test with bupivacain 0.5%. Five
      patients underwent direct repair of the pars interarticularis defects with hook
      screws, translaminar screws, and bone graft, while one patient received
      conservative treatment. All surgically treated patients had either good or
      excellent results at a mean of 34.4 months follow-up. One patient who was treated
      nonsurgically still complained of sport restriction at 16 months follow-up.
      Direct repair of multiple pars interarticularis defects after a positive staged
      pars infiltration test can restore anatomic stability, relieve back pain, and
      preserve a greater range of motion of the lumbar spine in young patients with
      intact disc height.

PMID- 11579619
TI  - Molecular neurobiology of addiction.
AB  - Addiction can be viewed as a form of drug-induced neural plasticity. One of the
      best established molecular mechanisms of addiction is the upregulation of the
      cAMP second messenger pathway, which occurs in many neuronal cell types in
      response to chronic administration of opiates or other drugs of abuse. This
      upregulation and the resulting activation of the transcription factor CREB appear
      to mediate aspects of tolerance and dependence. In contrast, induction of another
      transcription factor, termed delta FosB, exerts the opposite effect and may
      contribute to sensitized responses to drug exposure. Knowledge of these
      mechanisms could lead to more effective treatments for addictive disorders.

PMID- 11579620
TI  - The relationship between eligibility criteria for participation in alcohol brief
      intervention trials and other alcohol and health-related variables.
AB  - In clinical trials of brief interventions for alcohol use, individuals typically
      are defined as eligible for the research through meeting quantity-frequency (QF)
      of alcohol consumption criteria, alcohol-related problems criteria, or both. The
      purpose of this study was to evaluate preintervention and posttreatment
      differences among three groups of research participants eligible for
      participation in a brief intervention clinical trial by meeting the AUDIT total
      score criterion only, the QF criterion only, or both. The participants were 301
      men and women 21 years of age or older who presented for medical treatment at one
      of twelve primary care clinics and were screened for participation in the
      clinical trial. Participants completed an assessment protocol at preintervention
      and 1, 3, 6, 9, and 12 months postintervention. The analyses showed statistical
      differences among the three subgroups on three outcome dimensions of alcohol
      consumption, related consequences and behaviors, and medical complications; for
      both consumption and complications, the AUDIT + QF participants showed greater
      severity than participants in either of the other two groups. For consequences,
      AUDIT + QF participants scored higher than the QF participants on one variable
      constituting this dimension. The overall subgroup differences were maintained at
      six months in the consumption and consequences data. The implications of these
      findings for sensitivity of brief intervention trial design, the discovery of
      patient moderators of intervention effectiveness, and clinical practice are
      discussed.

PMID- 11579621
TI  - Gamma-hydroxybutyric acid: patterns of use, effects and withdrawal.
AB  - Gamma-hydroxybutyric acid (GHB) is gaining popularity as a drug of abuse. Reports
      of toxicity and lethality associated with GHB use have increased. This survey
      study was designed to identify patterns of GHB use, its effects, and withdrawal
      syndrome. A survey inquiring about the effects of GHB was administered to 42
      users. The results showed that GHB was used to increased feelings of euphoria,
      relaxation, and sexuality. Adverse effects occurred more frequently in daily
      users and polydrug users than in occasional GHB users. Loss of consciousness was
      reported by 66%, overdose by 28%, and amnesia by 13% of participants during GHB
      use and by 45% after GHB use. Three daily users developed a withdrawal syndrome
      that presented with anxiety, agitation, tremor, and delirium. Participants
      described GHB intoxication as having similarities to sedative-hypnotic or alcohol
      intoxication. Regular use has been shown to produce tolerance and dependence.
      Participants dependent on GHB reported using multiple daily doses around the
      clock. High frequency users appeared at the greatest risk for developing
      withdrawal delirium and psychosis after abrupt discontinuation of GHB use.

PMID- 11579622
TI  - Psychiatric care management for chronic addictive disorders: conceptual
      framework.
AB  - Coexisting mental and addictive disorders are common, and service systems are not
      well configured to treat them. Psychiatrists frequently feel lacking in skills to
      address both the addictive disorder and the mental illness. Although programs for
      treating "dual disordered" patients have been under development, specialized
      programs are likely to provide treatment for only a minority of patients.
      Furthermore, many patients either do not respond to them or simply refuse to
      participate. This article describes care management, a clinical approach that can
      be applied to coexisting disorders by any practitioner. Care management
      complements rehabilitation treatment and completes the continuum of care.

PMID- 11579623
TI  - Self-help strategies among patients with substance use disorders.
AB  - The objective of this study was to determine (1) the type and extent of self-help
      efforts among patients presenting for treatment of substance use disorders, and
      (2) the association of self-help with demographic and clinical characteristics. A
      retrospective report of life self-help methods, current demographic
      characteristics, and current and lifetime clinical characteristics was used. Six
      hundred and forty-two patients in treatment for substance use disorder were
      interviewed at one of two university medical centers with Alcohol-Drug Programs
      located within departments of psychiatry. A research associate (RA) interviewed
      patients regarding seven types of self-help involving specific, mutually
      exclusive behaviors and rated the patient's lifetime self-help methods. The
      patient, RA, and addiction psychiatrists provided demographic, familial, and
      clinical information. Most patients (78%) had tried one or more types of self
      help, with a mean of 2.7 methods per patient. They more frequently chose methods
      related to the substance (decreasing amounts or frequency, or changing substance
      type) or joining a self-help group than methods that involved changing friends,
      residence, or occupation/job/school. Certain patterns of self-help tended to
      occur together (e.g., changing substance frequency and dose), whereas others
      appeared more independent (e.g., joining a self-help group). Some self-help
      approaches occurred mostly in association with other methods rather than alone
      (e.g., changing occupation/job/school). More self-help was associated with higher
      socioeconomic class, more relatives with substance use disorder, greater severity
      of substance use disorder, and more treatment for substance use disorder. Self
      help tends to occur more often after exposure to addicted relatives or addiction
      treatment. Clinicians and public adult education should promulgate self-help
      methods in the general population.

PMID- 11579624
TI  - Predicting treatment response to naltrexone: the influence of craving and family
      history.
AB  - Naltrexone has repeatedly been shown to reduce drinking in alcohol-dependent
      patients. Previous clinical research suggests that naltrexone may be more
      effective at reducing drinking among patients with high levels of alcohol craving
      at the beginning of treatment. In addition, laboratory studies suggest that
      naltrexone may be more efficacious among patients with a high familial loading of
      alcohol problems. We explored both of these possibilities in the context of the
      first 12-week phase of a double blind, placebo-controlled naltrexone trial. A
      total of 121 patients were randomized to receive 100 mg/day naltrexone and 62
      patients were randomized to receive placebo. Both naltrexone and placebo were
      given in conjunction with a psychosocial intervention designed to be integrated
      with the use of pharmacotherapy. This intervention was administered by nurse
      practitioners. Overall, patients randomized to naltrexone reported drinking five
      or more drinks on fewer days than did placebo controls (p = .04). Interactions
      were observed between medication group assignment and both craving level prior to
      randomization (p = .02) and family loading of alcohol problems (p = .05). In both
      cases, the interaction was in the predicted direction. These data suggest that
      patients with high levels of alcohol craving or a strong family history of
      alcoholism are more likely to benefit from naltrexone treatment.

PMID- 11579625
TI  - Preadolescent children of substance-dependent fathers with antisocial personality
      disorder: psychiatric disorders and problem behaviors.
AB  - We compared psychiatric disorders and problem behavior scores in pre-adolescent
      children of fathers with alcohol or other drug dependence and ASP (SD+/ASP+),
      children whose fathers had substance dependence without ASP (SD+/ASP-), and
      children whose fathers were without either disorder (SD-/ASP-). SD+/ASP+ children
      showed elevated rates of major depression, conduct disorder, attention deficit
      hyperactivity disorder, oppositional defiant disorder, and separation anxiety
      disorder when compared to SD+/ASP- and SD-/ASP- children. SD+/ASP+ children had
      higher internalizing and externalizing problem behavior scores than the other two
      groups of children. The results suggest that SD+/ASP+ children are at significant
      risk for internalizing and externalizing psychopathology.

PMID- 11579626
TI  - Internet facilitation of opioid dependence.

PMID- 11579627
TI  - [Genome research and anticancer chemotherapy].
AB  - Worldwide research on the human genome is having a major impact on medical
      science and advanced medicine, although the detailed function and interaction of
      most genes remain unclear. The elucidation of human genome data makes it possible
      to take global views of biological processes and characteristics of cancer and
      individual drug response. This brings a number of new challenges such as genome
      based drug development and tailored cancer chemotherapy based on the individual
      genomic make-up. When a disease gene is identified, truly effective drugs
      targeting the genes can be developed. When biological characteristics such as
      polymorphism and gene expression profiles are closely related to drug response,
      an individually optimized drug therapy can be realized. cDNA microarray
      technology and new high-throughput single nucleotide polymorphism (SNP) screening
      offer great hope for such a global view by providing a systematic way to survey
      DNA and RNA variation. Evolutionary engineering techniques continue to be
      developed, which significantly promotes studies to understand molecular
      mechanisms causing diseases, novel disease genes, and genes related to drug
      response. Such progress in genome research and the functional analysis may
      revolutionize the anticancer chemotherapy world. The possible contribution of
      genome research to anticancer chemotherapy and problems of the day are reviewed
      herein.

PMID- 11579629
TI  - [Acute myeloid leukemia].
AB  - Acute myeloid leukemia (AML) has been treated with combination chemotherapy,
      hematopoietic stem cell transplantation (HSCT) and differentiation induction
      therapy. Intensive induction and consolidation therapy including high dose
      cytarabine (HDAC) is a widely used combination in chemotherapy in the USA and
      European countries. In Japan, the efficacy of HDAC needs to be evaluated under a
      good clinical trial. Stem cell source for HSCT has been expanded, and the number
      of peripheral blood stem cell transplantations is greater than that of bone
      marrow transplantation, especially for auto-transplantation. Despite some
      randomized clinical trials, we still do not know whether HSCT provides longer
      survival than chemotherapy for patients with AML when performed during their
      first remission. Differentiation therapy for acute promyelocytic leukemia (APL)
      using ATRA showed clear success in the treatment for AML. APL is stratified with
      its specific karyotype and morphology, and this stratification leads to the
      improvement of overall survival of patients with APL. Several clinical study
      groups in the world have studied prognostic factors and it has been shown that
      the chromosomal abnormality of AML cells is closely related to the response to
      the chemotherapy. The stratification of AML using these prognostic factors is
      incorporated in some clinical trials to determine whether this approach actually
      leads to better survival for patients with AML.

PMID- 11579630
TI  - [Chronic myelogenous leukemia].
AB  - STI571, a BCA-ABL tyrosine kinase inhibitor, has appeared in molecular targeted
      therapy as a new treatment option for patients with chronic myelogenous leukemia
      (CML) through rational drug development. In a phase I study in the USA, adverse
      effects were minimal. Complete hematologic response was observed in 98% of
      patients with chronic phase CML treated with a daily dose of 300 mg or more, and
      cytogenetic response was seen in 31% of patients. STI571 has substantial activity
      in the blast crisis of CML and Ph + ALL. Stem cell transplantation (SCT) may be
      compared with interferon-alpha (IFN-alpha) therapy from three analyses reported
      according to risk assessment. These studies indicated that SCT increased survival
      only in patients who were younger and at intermediate or high risk; however,
      survival with SCT in older patients at higher risk was no better than with IFN
      alpha therapy in a Japanese prospective study. An individualized risk assessment
      based approach is useful in prioritizing SCT and IFN-alpha in patients with
      chronic phase CML.

PMID- 11579631
TI  - [Multiple myeloma--advances in disease biology and implications for therapy].
AB  - Multiple myeloma (MM) is a systemic malignancy of pathologic plasma cells that is
      treatable with various chemotherapeutic agents and irradiation, but rarely
      curable. The mean age of affected patients is the mid-60s. Since the clinical
      presentation of multiple myeloma varies from asymptomatic to aggressive
      progression, there are many therapeutic options, such as follow-up without any
      treatment, and high-dose chemotherapy with stem cell transplantation. Recent
      advances in disease biology and implications for therapy are reviewed and
      summarized.

PMID- 11579632
TI  - [Recent progress in the treatment of malignant lymphoma].
AB  - The present state of the art and developments in the treatment for Hodgkin's
      disease (HD), follicular lymphoma (FL), MALT lymphoma, and aggressive non
      Hodgkin's lymphoma are reviewed. Four courses of ABVD therapy (ABVd therapy in
      Japan) followed by involved-field irradiation (IFRT), and 6 to 8 courses of ABVD
      (ABVd in Japan) are the current state art of the therapy for early stage HD and
      advanced stage HD, respectively. High-dose chemotherapy with autologous
      hematopoietic stem cell transplantation (auto-HSCT) is also the state of the art
      for refractory or relapsed HD within 1 year after complete remission (CR)
      produced by polychemotherapy. The prognosis of the patients with 3 or more
      International Prognostic Scores (IPS) is poor. New intensified polychemotherapy
      or auto-HSCT as up-front setting is under randomized phase III clinical trial in
      Europe and the USA. There is no state of the art therapy for indolent lymphoma
      including FL, or MALT. Promising results were reported from clinical studies
      using new anti-lymphoma drugs such as rituximab, iibritumomab, or purine analogs
      (cladribine and fludarabine), and auto-HSCT with effectively purged stem cells or
      allogeneic HSCT. These therapeutic strategies hold a possibility of cure for
      indolent lymphomas. Antibiotic treatment for Helicobacter pylori-positive
      localized gastric MALT lymphoma is the state of the art therapy. However, there
      is no standard therapy for advanced stage MALT lymphoma. Risk adapted therapy
      using the International Prognostic Index is essential for the treatment of
      aggressive NHL. Three courses of CHOP followed by IFRT for localized aggressive
      NHL and 8 courses of CHOP for the low-risk group of advanced stage aggressive NHL
      are the state of the art therapies, respectively. High-dose chemotherapy with
      auto-HSCT is also the state of the art for sensitive relapse patients with
      aggressive NHL. Although some clinical studies suggested that high-dose
      chemotherapy with auto-HSCT as up-front setting for high-intermediate or high
      risk group aggressive NHL is more effective than conventional chemotherapy, the
      efficacy remains to be determined. The development of new therapeutic strategies
      with combined use of molecular targeting drugs such as rituximab, or new anti
      lymphoma drugs such as purine analogs, and HSCT is desired for more effective
      therapy for refractory lymphomas.

PMID- 11579633
TI  - [Molecular specificity of nafamostat mesilate (FUT), a drug used for the
      treatments of DIC and acute pancreatitis and as an anticoagulant--the
      pharmacodynamics and pharmacological action].
AB  - Pharmacokinetic studies of nafamostat mesilate (FUT) were reviewed in the
      previous report (Jpn J Cancer Chemother 27 (5): 767-774, 2000). In this report,
      the molecular specificity of FUT for these pharmacological behaviors were
      reviewed. In this study, it became clear that benzene ring inserted between ester
      bond and guanidino group of the molecule and amidino group introduced in the
      opposite chain of guanidino group were found important for eliciting the
      molecular specificity of FUT.

PMID- 11579634
TI  - [Effect of combination chemotherapy with nedaplatin and 5-FU for head and neck
      squamous cell carcinoma].
AB  - Nedaplatin (254-S), which is a cisplatin (CDDP) analog, is an effective agent for
      head and neck squamous cell carcinoma (HNSCC). 254-S is expected to play an
      important role in neo-adjuvant chemotherapy (NAC) for HNSCC in place of CDDP. We
      have been using combination chemotherapy including CDDP, 5-FU, MTX and LV. The
      response rate and CR rate of this 4-drug combined chemotherapy are 87% and 33%.
      Thirty-six patients with HNSCC were treated with 5-FU, 800 mg/m2/day for 5 days
      and 254-S, 100 mg/m2 on day 4. Chemotherapy was discontinued in one patient
      because of allergic shock. Three patients showed a CR and 10 patients showed a
      PR. The response rate and CR rate of 254-S plus 5-FU chemotherapy were 37.1% and
      8.6%. These were inferior to those with the 4-drug combined chemotherapy.
      Fourteen percent of patients showed grade 3 leukocytopenia, and 17% showed more
      than grade 3 thrombocytopenia. The effect of combination chemotherapy of 254-S
      and 5-FU was inferior to that of the previous chemotherapy including CDDP, 5-FU,
      MTX and LV. Further study or another combination therapy including 254-S will be
      essential for improving efficacy against HNSCC.

PMID- 11579635
TI  - [Influence of peplomycin on pulmonary function (PaO2, %DLco) in patients with
      oral carcinoma].
AB  - The pathogenesis of pulmonary fibrosis (PF) induced by bleomycin and its
      derivative, peplomycin (PEP), is insufficiently understood. To prevent PF and to
      administer PEP safely, we examined the influence of PEP on pulmonary function in
      135 patients who underwent concomitant chemo (PEP + 5-FU)-radio (60Co) therapy
      and pulmonary function tests. In the inductive therapy, 5 mg of PEP was
      intramuscularly injected three times a week and a total of 41.6 +/- 14.3 mg was
      administered. Of the patients, 98 received oral azelastine hydrochloride (AZH, 4
      mg/day) during the inductive therapy with the aim of prophylaxis of PF. The
      oxygen partial pressure in arterial blood (PaO2) only slightly decreased from
      84.2 +/- 12.1 mmHg before treatment to 82.8 +/- 12.5 mmHg after treatment, while,
      carbon oxide diffusion (%DLco) decreased after treatment in most patients (p <
      0.001, by paired t test) with mean values before treatment of 106.3 +/- 24.5% and
      after treatment 99.5 +/- 24.9%. The decrease of %DLco was associated with the
      dose of PEP until about 40 mg but further decreases of %DLco were not prominent.
      In the patients who underwent oral AZH, the decrease of %DLco weaker than that in
      patients without AZH: the decrease rates of %DLco in the former and latter were
      4.3 +/- 9.4% and 14.1 +/- 15.9%, respectively. From the chest X-ray examination,
      mild PF was suspected in three patients but no advancement of PF or clinical
      symptoms were observed. From these results, it was concluded first that %DLco is
      more useful than PaO2 as the predisposing risk factor for PF, second that the
      decrease of %DLco depends on the dose of PEP until about 40 mg, third that AZH is
      expected to inhibit PEP-induced PF, and fourth that a small dose (20-40 mg) of
      PEP can be administered without inducing PF if care is exercised as to the
      patient's age, general condition and the value of %DLco in the use of PEP.

PMID- 11579636
TI  - [Repeated intraperitoneal chemotherapy for peritoneal dissemination from gastric
      carcinoma].
AB  - Repeated intraperitoneal chemotherapy (RIC) via an i.p. port system was carried
      out in 16 patients with peritoneal dissemination (P1) and in 10 with positive
      washing cytology (P0.CY1) from gastric carcinoma. CDDP dissolved in 500-1,000 ml
      of physiological saline solution was periodically administered via the i.p. port
      system. The change of washing cytology (CY), which was obtained from i.p. port,
      was examined before each administration as a indicator of the response. The
      average number of administrations was 5.7 and the average total dose was 301.7
      mg. As a result, a negative change of CY after RIC was found in 74% of patients,
      and also more than 80% of the response occurred within three administrations. The
      prognosis tended to be better in P0.CY1 patients than in P1 patients. In
      particular, the median survival time of the CY responders markedly improved as
      compared with non-responders (27.8 months versus 7.1 months). Although diarrhea
      and anorexia of grade 3 developed once in each patient, serious toxicities were
      not found. In conclusion, we consider RIC to be an effective therapy for P0.CY1
      among cases with peritoneal dissemination from gastric carcinoma.

PMID- 11579637
TI  - [Combination chemotherapy of doxifluridine plus mitomycin C for colorectal lung
      metastasis--phase II study].
AB  - PURPOSE: We conducted a multi-center study to investigate the usefulness of a
      combination drug therapy with doxifluridine (5'-DFUR) and mitomycin C (MMC) in
      colorectal cancer patients with lung metastasis. PATIENT AND METHODS: Subjects
      were advanced/recurrent colorectal cancer patients with lung metastasis, who
      underwent concomitant drug administration with 533 mg/m2/day of 5'-DFUR orally
      and 4 mg/m2/day of MMC every 2 weeks intravenously. RESULTS: Of 84 patients
      registered, 54 patients who were evaluable for tumor response showed results such
      as: complete response, one; partial response, 4; no change, 30; and progressive
      disease, 19, corresponding to a response rate of 9.3%. The median survival period
      of 54 patients was long at 473 days. The median administration days of 5'-DFUR
      was 201.5 days and the median number of MMC administrations was 14, indicating a
      long administration period of the combined therapy. The incidence of adverse drug
      reactions (ADRs) was 37.2% which included thrombocytopenia, 16.7%, and
      leukocytopenia, 11.5%; only a few ADRs were grade 3 or over. CONCLUSIONS: While
      combined therapy with 5'-DFUR and MMC resulted in a low response rate, the
      regimen suggested a survival effect in the patients.

PMID- 11579638
TI  - [Low-dose etoposide in a patient with adult T-cell leukemia/lymphoma who had
      severe complications].
AB  - A 76-year-old female had been followed in our hospital for dissecting aneurysm,
      cardiac failure, and cerebral infarction. Inguinal lymphadenopathy, anorexia, and
      weight loss were noted in June 1998. The histopathologic diagnosis of the
      biopsied lymph node was diffuse pleomorphic type non-Hodgkin's lymphoma with T
      cellular phenotype, and the patient was referred to our department. She had human
      T-lymphotropic virus type I seropositivity, and PCR of the pX lesion disclosed a
      monoclonal band. She was ultimately diagnosed as having adult T-cell
      leukemia/lymphoma (ATL/L, stage IV). Since she had many severe complications, she
      was given low-dose etoposide (LD-ETP, 50 mg/day). Atypical cells disappeared from
      the blood, and lymphadenopathy regressed. No major adverse reaction was observed
      after LD-ETP. She continued to receive intermittent LD-ETP, but she developed
      pneumonia in June 2000, and died in August 2000. Autopsy disclosed no residual
      lymphomatous lesions. These findings suggest that LD-ETP is a well tolerable and
      effective treatment in patients with ATL/L even if there are severe
      complications.

PMID- 11579639
TI  - [A case of mandibular gingival cancer T4N0M0 which markedly responded to a
      combined therapy of nedaplatin with 5-fluorouracil].
AB  - We recently experienced a case of mandibular gingival cancer T4N0M0 which
      markedly responded to a combination therapy of nedaplatin (254-S) with 5
      fluorouracil (5-FU). The patient was a 68-year-old male who visited our
      department with the main complaint of ulceration in the left mandibular gingiva.
      Biopsy revealed a moderately differentiated squamous cell carcinoma which
      extended to the mandible, mandibular gingiva, buccal mucosa, half tongue and oral
      floor on the left side of the face. As a neoadjuvant chemotherapy (NAC), 254-S at
      a dose of 100 mg/m2 was intravenously administered on day 1, while 5-FU at a dose
      of 700 mg/m2/day was intravenously administered from day 1 to 5 in succession.
      Hydration (2,000 ml/day) was performed from day 1 to 3. Adverse reactions
      observed included thrombocytopenia, anorexia, nausea, vomiting, stomatitis and
      SIADH, but no sign of renal dysfunction was observed. The clinical outcome was
      evaluated as CR. Surgery was performed later. Pathological examination of the
      extracted tissues showed tumor cells in the tongue only, indicating an excellent
      effect of this combination therapy of 254-S and 5-FU.

PMID- 11579641
TI  - [A case of esophageal small-cell carcinoma responding to chemotherapy with CTP
      11].
AB  - After examination of a 64-year-old man with dysphagia who consulted our hospital,
      a diagnosis was made an esophageal small-cell carcinoma. This tumor had
      infiltrated the aorta and upon further examination another carcinoma, trachial
      adenosquamous cell carcinoma was found. We judged this case to be inoperable. At
      first, 2 courses of systemic chemotherapy were administered by CDDP but this
      therapy had little effect. We know that CPT-11 is effective in the treatment of
      lung small-cell carcinoma, leading us to a decision to use CPT-11 for the second
      systemic chemotherapy. As a result of 8 courses, the tumor minification rate was
      64% with PR. After completing 13 courses, the patient could ingest any type of
      food. We observed grade 2 leukopenia as the only side effect. The patient
      survived for 1 year and 10 months after beginning the initial treatment. He
      transferred to another hospital for laser therapy for his trachial carcinoma. The
      patient died of brain metastasis. To date the treatment of patients with
      esophageal small-cell carcinoma with chemotherapy using CPT-11 has not been
      reported. We suggest that CPT-11 is an effective therapy in improving the
      condition of patients QOL with esophageal small-cell carcinoma.

PMID- 11579640
TI  - [A case of advanced non-small-cell lung cancer responding remarkably to weekly
      chemotherapy with paclitaxel].
AB  - We report a case of advanced non-small-cell lung cancer showing remarkable
      response to weekly administration of paclitaxel. The patient was a 63-year-old
      man who had IIIB advanced lung adenocarcinoma. Though he received one course of
      cisplatin and etoposide, the tumor was not reduced. In addition, because of his
      nauseous response, he no longer wanted to receive that chemotherapy. The
      chemotherapy regimen was therefore changed to weekly administration of
      vinorelbine, but this was not effective. Next, after changing the regimen to the
      weekly administration of paclitaxel, the tumor was remarkably reduced following 3
      courses. This case shows that weekly administration of paclitaxel may be an
      effective chemotherapy for non-small cell lung cancer not responsive to first
      line chemotherapy.

PMID- 11579642
TI  - [A case of breast cancer with bone marrow and liver metastases responding
      completely to low-dose weekly paclitaxel combined with toremifene].
AB  - A 36-year-old woman was admitted to our hospital because of general malaise in
      October 1999. She was diagnosed with bilateral breast cancer with bone marrow and
      liver metastases. Low-dose weekly paclitaxel (60 mg/body/week) combined with
      toremifene (120 mg/day) was started in December 1999. Myelofunction was recovered
      after 2 weeks of chemotherapy (CT), and the primary tumors and cervical/axillary
      lymphadenopathy disappeared after 4 weeks of CT. Bone marrow and liver metastases
      was no longer detected after 16 weeks of CT, and the case was evaluated as a
      complete response (CR). The same therapy has been performed for eight months and
      no evidence of recurrence has been observed.

PMID- 11579643
TI  - [A case of intra-peritoneal recurrence of colon carcinoma that responded
      remarkably to combined therapy of low-dose leucovorin and 5-fluorouracil].
AB  - We treated a patient with intra-peritoneal recurrent tumor from colon cancer who
      responded completely to chemotherapy of combined low-dose Leucovorin (LV) and 5
      fluorouracil (5-FU). The patient was a 75-year-old man. He underwent resection of
      the transverse colon, sigmoid colon and distal stomach for colon and gastric
      cancers. Nine months after the operation, his CEA level increased to 39.5 ng/ml
      and a CT scan revealed an intra-peritoneal tumor measuring about 5 cm. He
      received chemotherapy of 30 mg/day of LV that was injected in a bolus and 500
      mg/day of 5-FU that was given i.v. by continuous infusion for 10 days. At the end
      of 2 cycles of this regimen, CT scan demonstrated complete tumor remission and
      the patient's CEA level decreased to normal level. After an additional cycle of
      this regimen, he received modulated chemotherapy combined with l-Leucovorin and 5
      FU as an outpatient. However, after 3 months of treatment, a recurrent tumor was
      detected in the same portion and the first regimen was re-started for 5 days.
      After 4 cycles of treatment the tumor disappeared completely from a CT scan. It
      is important to investigate effective regimens that do not reduce the quality of
      life of the patient. This clinical experience suggests that a low-dose LV/5-FU
      therapy may be beneficial to patients with recurrent colon cancer. Further
      investigation is necessary to establish an effective regimen that can be given
      for a long period without adverse effects on quality of life.

PMID- 11579644
TI  - [Adverse effect of paclitaxel plus carboplatin combination therapy related to
      administration schedule in patients with ovarian cancer].

PMID- 11579645
TI  - [Tumor markers for colorectal cancer].
AB  - CEA and CA19-9 are the two most common tumor markers for colorectal cancer that
      are currently utilized clinically. The positive rate of CEA is 40-60% and that of
      CA19-9 is 30-50%. Simultaneous use of the two markers is useful in evaluating the
      therapeutic effect and monitoring the recurrence of advanced colorectal cancer.
      Surgical specimens may also provide useful information for the appropriate
      treatment of patients. Using surgically resected lymph nodes, we examined
      micrometastasis to assess the spread of the cancer cells and the malignant
      potential of colorectal cancer. Immunohistochemical analysis using anti
      cytokeratin antibody revealed no significant impact of micrometastasis on patient
      prognosis, while RT-PCR assay using CEA as a genetic marker suggested a positive
      value in predicting a rapid recurrence. Among various molecular markers, we found
      that CDC25B phosphatase was a powerful prognostic factor for colorectal cancer.
      Diagnosis of the existence and malignant potential of cancer cells, together with
      serum tumor marker levels, may help to construct a more useful system for the
      better treatment of colorectal cancer.

PMID- 11579646
TI  - Use of topical ketanserin for the treatment of ulcers in leprosy patients.
AB  - A comparative study was carried out in which 66 leprosy patients with ulcers were
      randomly divided in two groups of 33 patients each: Group A (experimental group)
      was treated with ketanserin gel (2%) and group B with clioquinol cream and/or
      Lassar paste during a three month period. At the end of the study, when ulcer
      sizes in the two groups were compared, the group treated with topical ketanserin
      showed superior results (p < 0.001 using Kolmogorov-Smirnov's test). We conclude
      that the drug is useful as coadjuavant treatment for healing ulcers in these
      patients.

PMID- 11579647
TI  - Lot quality assurance sampling (LQAS) for monitoring leprosy elimination in an
      endemic district in Tamilnadu.
AB  - This paper examines whether the health administration can use lot quality
      assurance sampling (LQAS) for identifying high prevalence areas for leprosy for
      initiating necessary corrective measures. The null hypothesis was that leprosy
      prevalence in the district was at or above ten per 10,000 and the alternative
      hypothesis was that it was at or below five per 10,000. A total of 25,500
      individuals were to be examined with 17 as an acceptable maximum number of cases
      (critical value). Two-stage cluster sample design was adopted. The sample size
      need not be escalated as the estimated design effect was 1. During the first
      phase, the survey covered a population of 4,837 individuals out of whom 4,329
      (89.5%) were examined. Thirty-five cases were detected and this number far
      exceeded the critical value. It was concluded that leprosy prevalence in the
      district should be regarded as having prevalence of more than ten per 10,000 and
      further examination of the population in the sample was discontinued. LQAS may be
      used as a tool by which one can identify high prevalence districts and target
      them for necessary strengthening of the programme. It may also be considered for
      certifying elimination achievement for a given area.

PMID- 11579648
TI  - Hepatic and haematological adverse reactions associated with the use of multidrug
      therapy in leprosy--a five year retrospective study.
AB  - This study analyses retrospectively some of the risks associated with the use of
      WHO-multidrug therapy (MDT) in Sri Lanka. Case records of 3,333 new cases of
      leprosy attending the Central Leprosy Clinic in Colombo during 1991-1995, were
      analysed for adverse drug reactions involving the liver and blood. There were 81
      reports of suspected hepatic or haematological adverse reactions associated with
      the use of MDT, of which 39 were classified as haemolytic anaemia, 25 as toxic
      hepatitis, 2 as methaemoglobinaemia and 15 as anaemia. Dapsone, was incriminated
      in the majority of adverse reactions (72%). Adverse drug reactions were more
      common in female than male subjects (55% vs 45%; P < 0.5), but there was no
      significant differences between the age groups. Majority of adverse reactions was
      seen within the first three months of initiation of MDT. This study in no way
      undermines the benefits of MDT but highlights the risks and suggests measures to
      minimize these risks.

PMID- 11579649
TI  - A comparative trial of single dose chemotherapy in paucibacillary leprosy
      patients with two to three skin lesions.
AB  - A multicentric, double-blind, controlled, clinical trial was carried out to
      compare the efficacy of a combination of rifampicin 600 mg plus ofloxacin 400 mg
      plus minocycline 100 mg (ROM) administered as single dose with that of standard
      WHO/MDT/PB six months regimen. The study subjects were 236 previously untreated,
      smear-negative patients, without nerve trunk involvement and having only two or
      three skin lesions. Randomization was done on individual patient basis. Results
      were analyzed for mean clinical score for improvement, marked clinical
      improvement and complete clinical cure at the time of release from treatment and
      at 12 months and 18 months of follow-up. Clinical improvement was seen in most
      patients in both regimens. Marked improvement (i.e., more than 90% reduction in
      clinical score) at 18 months was seen in 46.2% and 53.4% of the patients treated
      with ROM and standard regimens, respectively. But, significant difference in
      favour of standard PB regimen was seen in patients with three skin lesions and in
      patients in whom more than one body part was affected. Reversal reaction and
      adverse drug reactions were minimal in both groups.

PMID- 11579650
TI  - Protocol for motor function assessment in leprosy and related research questions.

PMID- 11579651
TI  - Bullous necrotizing fixed drug eruption with hepatitis due to rifampicin.

PMID- 11579652
TI  - Tetanus in a patient with lepromatous leprosy.

PMID- 11579653
TI  - Rifampicin-induced erythema nodosum leprosum-like eruption in borderline
      lepromatous leprosy.

PMID- 11579654
TI  - Borderline tuberculoid leprosy with Darier's disease.

PMID- 11579655
TI  - Report of the workshop on "Challenges before leprosy-affected persons" held on
      March 3, 2001 at Richardson Leprosy Hospital, Miraj (Maharashtra).

PMID- 11579656
TI  - Psychotherapeutic approaches to children in foster care: guidance from attachment
      theory.
AB  - The diverse psychological and emotional problems of foster children are reviewed,
      and an explanatory, interactional model based upon the key concepts of
      developmental psychopathology is described. The constructs of the internal
      working model and interpersonal schema, derived from attachment theory, are
      pathogenic mechanisms that contribute to the emergence of psychopathology in this
      population. The paper presents a general orientation to therapeutic work with
      foster children and describes some specific interventions based upon this
      interactional model. While attachment theory has much to offer clinicians,
      insecure attachment is just one of a number of risk factors; a comprehensive
      approach, both in terms of conceptualizing foster childrens' problems and
      treating them, is essential.

PMID- 11579657
TI  - The relationship of maternal and child HIV infection to security of attachment
      among Ugandan infants.
AB  - This study was designed to examine the relationship of maternal and child human
      immunodeficiency virus (HIV) infection to the security of attachment of Ugandan
      infants. The attachment patterns of two groups of Ugandan mother-infant pairs: 35
      HIV-positive mothers and their infants and 25 HIV-negative mothers and their
      infants were compared. We tested the hypothesis that infants of HIV-positive
      mothers would demonstrate less secure attachment as measured by the Waters
      Attachment Q-set than infants of HIV-negative mothers. No differences were found
      in the security of attachment of infants of HIV-positive versus HIV-negative
      mothers. Infants of HIV-positive mothers with Acquired Immunodeficiency Syndrome
      (AIDS) were less securely attached than infants of mothers without AIDS. These
      findings underscore the relationship of infant security of attachment to maternal
      HIV infection in the presence of AIDS-related symptoms but not to asymptomatic
      maternal HIV infection.

PMID- 11579658
TI  - Serotonin mediated cluster headache, trigeminal neuralgia, glossopharyngeal
      neuralgia, and superior laryngeal neuralgia with SAD chronicity.
AB  - Cluster headache is a rare and severe pain syndrome with elusive pathophysiology.
      Serotonin pathways within the brainstem may be implicated in cluster headache
      with seasonal affective disorder and a subset of cranial nerve neuralgias. We
      describe and chronicle a syndrome consisting of cluster headache, seasonal
      affective disorder, with associated trigeminal, glossopharyngeal, superior
      laryngeal neuralgias in an 11-year-old female. Pharmacologic interventions for
      this patient were examined in conjunction with current classification, location
      and function of serotonin receptors. Etiology is postulated as mixed cranial
      nerve excitation via endogenous 5-HT (agonist) activity of 5-HT3 receptors within
      the nucleus tractus solitarius and trigeminal tract nucleus.

PMID- 11579659
TI  - Depressive disorder in preschool children: patterns of affective organization.
AB  - In the present study the authors attempt to identify the pattern of depressive
      problems in children aged 3 to 6 years by employing a new rating scale (The
      Preschool Children Depression Checklist). Depressive symptoms were expressed in
      the form of 32 questions that cover an array of depressive behaviors as
      manifested in this age range. A factor analysis was carried out on 156 checklists
      submitted to the teachers of the control group in order to identify early
      affective behavioral patterns of the depressive disorder. Results confirmed the
      hypothesis that a coherent emotional structure underpins children's manifest
      behaviors. Three factors were empirically derived. These factors seem to be
      particularly important since statistical comparison showed significant
      differences among factor scores of a sample of children who met diagnosis of
      depression, a sample of children who met diagnosis of anxiety disorder, a sample
      of control children.

PMID- 11579660
TI  - The differential diagnosis of impaired reciprocal social interaction in children:
      a review of disorders.
AB  - Impairment in reciprocal social interaction in children that is less severe than
      autism can be difficult to diagnose due to the variety of developmental pathways
      that may lead to this problem. Seven childhood disorders are reviewed that
      include impaired reciprocal interaction: multisystem developmental disorder,
      nonverbal learning disability syndrome, semantic-pragmatic disorder, attachment
      disorders (including a developmental theory of limbic system damage), multiplex
      developmental disorder, schizoid personality disorder, and pervasive
      developmental disorder not otherwise specified. Clarification is needed for most
      of the disorders in the areas of operationalized criteria, assessment tools, and
      documenting causal relationships.

PMID- 11579661
TI  - A developmental approach to pediatric environmental health.
AB  - Children cannot be considered "little adults" in the field of environmental
      medicine. There are differences in exposures, pathways of absorption, tissue
      distribution, ability to biotransform or eliminate chemicals from the body, and
      responses to chemical and radiation. The differences vary with the developmental
      stages of the child. Children all respond differently to environmental toxicants.
      Knowledge, although rapidly increasing, is still incomplete regarding the impact
      of the environment on children. As health care providers, prevention is an ally
      but must be approached differently at each stage of a child's life.

PMID- 11579662
TI  - The clinical presentation of environmental health problems and the role of the
      pediatric provider. What do I do when I see children who might have an
      environmentally related illness?
AB  - The practice of environmental health is concerned with the protection of the
      community. There are a number of tools used for assessment of environmental
      hazards, but environmental health is most reliant on the use of risk assessment.
      Risk assessment is a set of tools used to assess hazards on a community level,
      based on human studies, ecological studies, or toxicity testing of animals.

PMID- 11579663
TI  - Resources for pediatricians. How do I answer questions from parents, patients,
      teachers, and others?
AB  - Most pediatricians do not have special training in pediatric environmental
      health, but environmental exposures are among parents' top concerns for their
      children. Parents may come to their pediatricians seeking advice about symptoms
      that they think may be related to an environmental hazard. They may worry about
      exposures even if their children have no symptoms. Occasionally, pediatricians
      may diagnose an illness caused by an environmental exposure but may not be
      familiar with the illness because it is uncommon.

PMID- 11579664
TI  - Parents worried about breast milk contamination. What is best for baby?
AB  - Breast milk contamination may concern parents who are worried about their
      infant's exposure to environmental or occupational chemicals. This article
      examines the risks posed by chemicals in breast milk compared to the risks of
      formula feeding. In addition, this article provides guidance to health care
      professionals about how to evaluate maternal exposures that may influence breast
      milk quality. A guide to assessing potential exposures at home and in the
      workplace is provided.

PMID- 11579665
TI  - Is the water safe for my baby?
AB  - Children's behavior and physiology place them at unique risk from waterborne
      microbial and chemical contaminants. This article reveals children's
      susceptibility factors and the microbial and chemical contaminants of greatest
      importance to this age group. It also provides a primer on water treatment and
      alternatives to tap water. This article concludes with recommendations and
      resources to aid the practicing pediatrician in addressing patient concerns about
      drinking water.

PMID- 11579666
TI  - Indoor air pollutants in homes and schools.
AB  - Exposure to the four indoor air pollutants mentioned in this article may cause
      illnesses and fatalities in children. It is important for pediatricians to be
      aware of each of them and to remove children from environments contaminated with
      these pollutants. Guidance about monitoring the indoor air and interpreting the
      results is difficult to find. A chart of proposed guidelines may help the
      pediatrician faced with an indoor air problem (Table 1).

PMID- 11579667
TI  - Outdoor air pollution. Asthma and other concerns.
AB  - Despite governmental efforts to improve the quality of outdoor air, a significant
      number of children growing up in the US are exposed to airborne pollutants. It is
      now recognized that infants generally at risk for atrophy when exposed to
      specific environmental airborne pollutants are more likely to develop asthma.
      Once asthma is established, airborne pollutants are important triggers in causing
      exacerbations. Airborne ozone and suspended articles are the two most important
      criteria pollutants with respect to exposure prevalence and suspected adverse
      health effects in US children. Pediatricians should be involved both in community
      advocacy programs to improve air quality and as knowledgeable practitioners in
      discussing practical air pollution avoidance strategies with patients and their
      families.

PMID- 11579668
TI  - Pesticides in children.
AB  - Children are exposed to a wide range of pesticides, including insecticides,
      herbicides, fungicides, and rodenticides. They differ from adults in their
      exposures and responses to exposures. Acute and chronic toxicity are discussed,
      and important chronic effects, such as carcinogenesis, endocrine disruption, and
      neurodevelopment effects are reviewed. The state of laws and regulations are also
      discussed. Recommendations are made to pediatricians regarding treatment and
      advising families regarding avoidance of pesticide exposures and their effects.

PMID- 11579669
TI  - Developmental neurotoxicity. Illustration of principles.
AB  - The magnitude of the problem of neurodevelopmental disorders is enormous.
      Frequently, the mechanism of injury is unknown. In this article, several common
      developmental neurotoxins are discussed, and the function of one cell adhesion
      molecule, L1, will be reviewed to illustrate the principles of developmental
      neurotoxicology. L1 is critical for proper central nervous system development.
      Similarities between patients with fetal alcohol syndrome and with L1 mutations
      suggest that the mechanism of developmental neurotoxicity of ethanol is partly
      due to effects on L1 cell adhesion molecule.

PMID- 11579670
TI  - Environmental exposure and cancer in children. A conceptual framework for the
      pediatrician.
AB  - Ultimately, after gathering and assessing all available evidence, pediatricians
      and health care policymakers must make informed decisions on whether exposure to
      a specific agent has the potential to cause cancer in children. In the case of
      DES, for which the results were clear, there was no question that the drug should
      be taken off the market; however, most cases of suspected carcinogens lack such
      clear evidence documenting cause and effect. An example of a murky topic is the
      suspected relationship between residential electromagnetic fields (EMFs) and
      childhood cancer. Epidemiologic and biologic researchers have tried for more than
      2 decades to determine whether exposure to relatively high levels of EMFs poses
      health hazards, especially cancer in children. Although the preponderance of
      evidence favors a judgment that this ubiquitous environmental exposure is
      harmless, concerns remain in many public circles and some scientific ones. Any
      proposed intervention to remove a potentially carcinogenic agent must be weighed
      against the cost and inconvenience to the affected community. Pediatricians are
      placed in a vulnerable position when faced with questions of a carcinogenic
      potential because of the frequency of claims in the popular literature stating
      that exposure to a certain product or food is associated with an increased risk
      for cancer in adults and possibly children. When such studies are published or,
      more often, released to the press, the strength of the evidence for a causal
      association with cancer, coupled with the context of the study, should be
      considered as a reasonable starting point. Better communication models of
      disseminating cancer-risk information are needed so that the public understands
      the difference between a weak study that appeared on the local news with little
      evidence to support a cause-and-effect relationship versus a well-designed study
      that was published in a peer-reviewed journal and indicates a likely cause-and
      effect association.

PMID- 11579671
TI  - Endocrine disruption in sexual differentiation and puberty. What do
      pseudohermaphroditic polar bears have to do with the practice of pediatrics?
AB  - What do pseudohermaphroditic polar bears and girls with premature breast
      development have in common? Hormones. Sexual differentiation and the initiation
      of secondary sexual characteristics, such as breast growth, are both under the
      control of the sex hormones estrogen and androgen. Abnormal differentiation of
      the internal or external genitalia in bears and early onset of breast development
      in girls also may have a common element--exposure to environmental hormones.

PMID- 11579672
TI  - The built environment and children's health.
AB  - The built environment embraces a wide range of concepts, from the design and
      integrity of housing, to land-use urban planning. A high-quality environment is
      essential for children to achieve optimal health and development. Building and
      land-use policies, including the quality and design of a child's physical
      environment, can cause or prevent illness, disability, and injury, and can
      degrade or preserve natural resources. Though many common pediatric conditions
      such as obesity, asthma, and lead poisoning, as well as injuries, are associated
      with risk factors within a child's built environment, this issue has received
      little attention from researchers or policymakers. This new field is ripe for
      etiologic and prevention research, and we need pediatric advocates to speak out
      for children's needs within this arena.

PMID- 11579673
TI  - Links between the social and physical environments.
AB  - This article proposes a model for understanding the links between children's
      health and the social and physical environment. School is the principal setting
      explored as a way of illustrating the issues. Three case examples of school
      related problems are presented and actions that pediatricians and others may take
      are outlined.

PMID- 11579674
TI  - Adolescent occupational exposures and pediatric-adolescent take-home exposures.
AB  - Thousands of adolescents are employed and routinely incur occupational exposures
      as part of their work. Case reports of adolescent exposure-related fatalities and
      illness, coupled with observational studies of chemical and other exposures with
      potential health risks, create a strong case for better tracking of work-related
      exposures and illness, better training for all working adolescents, education of
      their parents about risks, more clinical involvement in the health and safety of
      working adolescents, and advocacy for safer adolescent work environments. Because
      adolescents are neither children nor adults, much research is needed to clarify
      exposure patterns and risks; however, existing data on adolescent occupational
      injury and knowledge of exposures to adults in similar work environments permit
      immediate interventions. The most applicable information from the growing
      knowledge of environmental health in young children also can be borrowed and
      applied, especially to younger workers, such as those on farms, who may be
      children rather than adolescents. Crucial to future protection of working youth
      from occupational exposures are application of knowledge that already is
      possessed about occupational risks to adults, a cultural change in the way the US
      population views risks of chemical exposures, and improved occupational health
      and safety protection for all adult workers. Improving occupational health for
      working adolescents may be more politically acceptable and thus feasible than
      starting with adults, but ultimately the two are linked inextricably. These are
      new realms for pediatricians, but pediatrician input is needed greatly on all of
      these levels.

PMID- 11579675
TI  - Children. The unwitting target of environmental injustices.
AB  - Children have little control over where they live, what they eat, the financial
      circumstances of their families, or the developmental activities and behaviors
      that make them vulnerable to environmental contaminants. Minority and poor
      families disproportionately live in communities with landfills, hazardous waste
      facilities, incinerators, industrial plants, and old housing with poor indoor air
      quality and lead-based paint. Residents of these communities are also more likely
      than are more affluent communities to consume fish on a regular basis from local
      waters, many of which have banned fishing. Consequently, these children and their
      families are exposed more frequently than are children in other communities to
      potentially dangerous chemicals that can affect health. Data indicate that poor
      and minority children have higher rates of asthma, elevated blood lead levels,
      learning disabilities, and hyperactivity than do non-minority and more affluent
      children. When a group of people is exposed unfairly and inequitably to toxins in
      their communities, workplaces, and schools, a phenomenon called environmental
      discrimination or environmental racism exists. Environmental justice is a US
      governmental remedy that requires the application of fair strategies and
      processes in the resolution of inequality related to environmental contamination.
      The US response resulted in the establishment of offices of Environmental Justice
      within the EPA and ATSDR and passage of important legislation and policies, such
      as the Community Planning and Right-to-Know Act of 1986, Executive Order 12898
      (Federal Actions to Address Environmental Justice in Minority Populations), and
      Executive Order 13045, a parallel order to protect low-income and minority
      children from actual and potential environmental hazards. Communities and
      advocacy groups play an important role in promoting healthier environments for
      children. Frequently, low-income and minority communities are perceived as less
      powerful, less organized, and ill equipped to defend against actual and potential
      sources of environmental contamination. Health care professionals are in a
      strategic position to assist with community development, organizing, and
      empowerment through educational programming, networking, and supporting other
      activities that bring attention to the plight of environmentally vulnerable
      communities.

PMID- 11579676
TI  - Children's environmental health. Lessons from the past and prospects for the
      future.
AB  - Environmental pediatrics is an area of pediatric medicine that has come a long
      way in the past 50 years. It has risen to importance in parallel with two
      developments: (1) the conquest in the industrialized nations of the major
      infectious diseases and their replacement by chronic conditions, such as asthma,
      cancer, developmental disabilities, and birth defects as the primary causes of
      illness and death in children and (2) the growing recognition that chemicals in
      the environment are responsible, at least in part, for these changes in patterns
      of disease. The challenge now to environmental pediatrics is to better understand
      the impact of chemical substances on the patterns of health and disease in
      children and to design evidence-based approaches to the treatment and prevention
      of childhood disease of environmental origin.

PMID- 11579677
TI  - High prevalence of RET tyrosine kinase activation in Mexican patients with
      papillary thyroid carcinomas.
AB  - RET/PTC oncogene expression is restricted to papillary thyroid carcinomas (PTC).
      At least three forms of this oncogene have been described. These are generated by
      the rearrangement of the 5'-terminal region of different expressed genes with the
      tyrosine-kinase (TK) domain of the ret proto-oncogene. Several studies showing
      the correlation between the expression of this oncogene, clinical outcome, and
      histological subtypes have been published. Thirty-five paraffin-embedded PTC
      samples from patients without a history of radiation exposure were studied.
      Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to determine
      a possible correlation between RET activation, clinical outcome, and tumor
      subtype. Almost half of the studied cases presented with tumoral extension or
      metastases. Ret gene transcripts and protein were found in all PTC variants as
      well as in their corresponding metastases. In contrast, none of the follicular
      adenomas, goiters, or normal follicular cells from the thyroid gland showed
      evidence of ret activation. We observed a high frequency of ret expression in
      PTCs, suggesting that ret activation is a common event in nonradiation-related
      PTC from Mexican patients.

PMID- 11579678
TI  - Analysis of beta-catenin mutations and alpha-, beta-, and gamma-catenin
      expression in normal and neoplastic human pituitary tissues.
AB  - The cadherin-catenin system mediates Ca(2+)-dependent cell-cell adhesion, and
      genetic alterations in these molecules play a significant role in multistage
      carcinogenesis. Mutations in the beta-catenin gene, mostly affecting exon 3, have
      been detected in malignant cell lines and in primary tumors. Immunohistochemical
      abnormalities in alpha-, beta-, and gamma-catenin have been reported in malignant
      and benign tumors, and nuclear localization of beta-catenin has been associated
      with mutations in exon 3 of this gene. Mutational analysis of exon 3 of the beta
      catenin gene was undertaken by polymerase chain reaction (PCR) and sequencing
      using genomic DNA extracted from frozen tissues, including 4 normal pituitaries,
      22 pituitary adenomas, and one pituitary carcinoma. Frozen sections from these
      cases were used for immunohistochemical detection of beta-catenin. We also
      analyzed immunohistochemical expression of alpha-, beta-, and gamma-catenin by
      paraffin sections from 154 pituitary tumors, including 148 adenomas and 6
      carcinomas. Genomic DNA was extracted from paraffin sections of 2 gonadotroph
      tumors showing nuclear staining for beta-catenin and was used for PCR and
      sequencing of exon 3 of the beta-catenin gene. No mutations in exon 3 of the beta
      catenin gene were found in any of the 23 cases analyzed by PCR and sequencing. In
      addition, the 2 cases studied by paraffin section immunohistochemistry, with
      nuclear staining for beta-catenin, were negative for mutations in this exon.
      Normal pituitary expressed all three catenin proteins. Immunostaining usually
      showed a membranous pattern of reactivity and was generally stronger in normal
      pituitary than in the adjacent adenomas. Stains for alpha-catenin were positive
      in fewer tumors than for beta-catenin. The lowest frequency immunopositive tumors
      and the weakest immunostaining was for gamma-catenin. All medically treated
      prolactinomas were negative for gamma-catenin, whereas treated growth hormone
      adenomas were less often positive for both alpha- and gamma-catenin than for
      untreated tumors. The percentage of positive cases for beta-catenin was the same
      in these two groups. Most pituitary carcinomas were negative for both alpha- and
      gamma-catenin but were beta-catenin positive. These results indicate that (i)
      mutations in exon 3 of the beta-catenin gene are uncommon in pituitary tumors,
      and (ii) expression of alpha-, beta-, and gamma-catenin is decreased in pituitary
      adenomas compared to normal pituitary tissues.

PMID- 11579679
TI  - Immunocytochemical localization of prohormone convertase 1/3 and 2 in
      gastrointestinal carcinoids.
AB  - Gastrointestinal carcinoids are derived from the diffuse intestinal endocrine
      system and may produce amines and many peptides, including serotonin,
      chromogranin A (CGA), and tachykinins. Most peptide hormones are synthesized as
      bigger prohormones, which are processed to smaller active hormones by prohormone
      convertases (PCs). A total of 35 cases of gastrointestinal carcinoids, including
      gastric, duodenal, small intestinal, appendiceal, and large intestinal
      carcinoids, were immunocytochemically stained for serotonin, CGA, and PC 1/3 and
      2, in order to colocalize CGA and PCs in the carcinoids. All carcinoids were
      positive for CGA and PCs. Carcinoids that stained strongly for CGA were generally
      weakly stained for PCs and those weakly staining for CGA were more strongly
      stained for PCs in the majority of the small and large intestinal tumors.
      Gastrointestinal carcinoids were positive for CGA and PCs, and the presence of
      PCs may suggest that the conversion of peptide prohormones to smaller peptide
      hormones occurs in gastrointestinal carcinoids. PCs immunocytochemistry may be
      added as a new phenotypic characterization for gastrointestinal carcinoids.

PMID- 11579680
TI  - Somatostatin type 2A receptor immunoreactivity in human pancreatic
      adenocarcinomas.
AB  - Somatostatin and its analogs have been included in experimental treatment
      protocols for advanced pancreatic adenocarcinoma based on their known
      antisecretory and antiproliferative properties. Somatostatin receptor type 2
      (sstr2A) mediates antiproliferative actions of somatostatin and has the strongest
      affinity to the therapeutically used somatostatin analog--octreotide. We
      investigated localization of sstr2A in 27 pancreatic adenocarcinomas in relation
      to tumor histological features and neuroendocrine differentiation confirmed by
      immunoreactivity for chromogranin A (CgA), chromogranin B (CgB), or somatostatin.
      Immunoreactivity for sstr2A generally coincided with tumor neuroendocrine
      differentiation demonstrated by staining for CgA and was present on the cell
      membranes of pancreatic islet cells and endocrine cells occasionally present in
      the wall of normal pancreatic ducts. Thirteen pancreatic adenocarcinomas
      contained cells immunoreactive for sstr2A in numbers ranging from occasional
      single cells, cell clusters, or carcinoma duct segments. In two cases, cells
      immunoreactive for sstr2A and CgA represented more than 30 and 10% of the total
      tumor cell population (case 1 and 15, respectively). Case 1 fulfills the
      diagnostic criteria of mixed ductal endocrine carcinoma. We conclude that
      immunohistochemical staining for a generic neuroendocrine marker such as CgA
      would facilitate identification of a subgroup of pancreatic adenocarcinomas
      expressing sstr2A receptors. Future studies need to evaluate the responsiveness
      of these tumors to somatostatin analogue treatment.

PMID- 11579681
TI  - Paucicellular variant of anaplastic thyroid carcinoma: report of two cases.
AB  - The paucicellular variant of anaplastic carcinoma is an infrequent type of
      thyroid tumor. It was described as a tumor characterized by very low cellularity
      and prominent fibrosis, probably secondary to extensive infarction. These
      features could lead to an erroneous diagnosis of Riedel's thyroiditis. In this
      paper, we report the clinical and pathological features of two new cases of this
      unusual entity. Tumor cells were negative for thyroglobulin immunostaining and
      positive for keratins and p53. Although the number of reported cases is small,
      the cumulative data on these two cases and the previously reported ones lead us
      to suggest that the paucicellular variant may occur in younger patients than the
      conventional anaplastic thyroid carcinoma and that the tumor may be associated
      with a less aggressive tendency to local progression and metastasis.

PMID- 11579682
TI  - Correlation between PCNA expression and AgNOR dots in pituitary adenomas.
AB  - Nucleolar organizer regions are segments of DNA associated with argyrophilic
      proteins (AgNORs). Our previous findings showed that the number, the area, and
      the intranuclear localization of AgNOR dots differ according to tumor
      aggressiveness and to the hormone-immunopositivity of pituitary adenomas.
      Proliferating cell nuclear antigen (PCNA) is a nuclear protein, whose expression
      is correlated with cell proliferation. The aim of the present paper was to
      examine PCNA-labeling indexes in pituitary adenomas and to correlate them with
      AgNOR dots in various immunohistochemical types of the tumors. Histological
      slides from 32 pituitary tumors and one normal pituitary were silver-stained and
      analyzed with a computerized system for microscopic image analysis. We found that
      the percentage of PCNA-positive cells did not differ significantly among examined
      groups of monohormonal adenomas. However, tumors immunopositive for alpha-subunit
      (alpha-SU) showed a significantly higher (p < 0.05) PCNA index than adenomas
      immunonegative for that unit. PCNA index in recurrent tumors was significantly
      higher than in primary adenomas. There was a moderate positive correlation
      between the PCNA index and the mean area of AgNOR dots and a similar correlation
      between the PCNA index and the area of the biggest dot in the nucleus. The
      obtained results reveal that the PCNA indexes and estimated parameters of AgNOR
      dots differ according to tumor aggressiveness.

PMID- 11579683
TI  - GH-, PRL-, POMC-, beta-TSH-, beta-LH-, beta-FSH-mRNA in gonadotroph adenomas of
      the pituitary by in situ hybridization in comparison with immunostaining and
      clinical data.
AB  - In situ hybridization (ISH) enables the visualization of specific mRNA for
      pituitary hormones. Our collection consists of 40 surgically removed pituitary
      adenomas that were classified as follicle stimulating hormone/luteinizing hormone
      (FSH/LH) cell adenomas by structure and by immunostaining (IH) for all pituitary
      hormones. All forty adenomas were regarded as clinically inactive. The aim of our
      study was to examine nonfunctioning adenomas by ISH for demonstration of mRNAs
      for all pituitary hormones. The results were compared with proliferation markers,
      invasiveness and clinical data. ISH detected signals for all pituitary hormones
      at a range of 30% for prolactin (PRL) to 85% for proopiomelanocortin (POMC). mRNA
      for beta-FSH was detected in 70% and beta-LH mRNA in 43% of adenomas. Thirty
      three percent of adenomas revealed negative mRNA detection for beta-LH but
      positive hormone content. The majority of adenomas (75%) expressed more than two
      mRNAs simultaneously, mostly the combination of POMC mRNA together with beta-FSH
      mRNA and one to four others. Comparison with clinical data showed no significant
      differences except for one adenoma with a high Ki-67 index (> 2.1% positive
      nuclei). This adenoma showed very high signals for PRL and beta-TSH mRNA.

PMID- 11579684
TI  - Immunohistochemical analysis of p27 (Kip1) in human pituitary glands and in
      various types of pituitary adenomas.
AB  - p27 (Kip1) plays regulatory roles in the cell cycle by inhibiting the activity of
      cyclin dependent kinases (CDKs). This immunohistochemical study is aimed at
      elucidating the expression of p27 in human pituitary and in various types of
      pituitary adenomas in order to clarify its role in the regulation of
      proliferation. Sixteen normal pituitary glands and 179 human pituitary adenomas
      were used for immunohistochemical studies. The tissues were fixed in 10% formalin
      and embedded in paraffin. Indirect peroxidase method was performed after heat
      induced antigen retrieval using a monoclonal antibody against p27 protein. p27
      protein was expressed in the nuclei of all 16 normal human pituitary glands. p27
      protein was also expressed in 128 of 179 cases of pituitary adenomas (71.5%). A
      marked decrease of p27 expression was noted in ACTH-secreting adenomas, 8/20
      (40.0%), compared with other types of pituitary adenomas--GH-secreting adenomas,
      35/46 (76.1%); PRL-secreting adenomas, 22/33 (66.7%); TSH-secreting adenomas,
      8/11 (72.7%); and nonfunctioning adenomas, 55/69 (79.7%). These results suggest
      that p27 may play some role in the regulation of proliferation in all types of
      pituitary adenomas. The lower levels of p27 in ACTH-secreting adenoma is of
      particular interest with respect to the intermediate lobe-derived pituitary tumor
      developed in p27 knockout mice.

PMID- 11579686
TI  - [Advances in the development of new antitubercular agents from a group of
      orthocondensed heterocyclic compounds. Part 2. Substances containing more
      nitrogen atoms in the 6-membered ring].
AB  - Tuberculosis and other mycobacterial diseases are considered to be one of the
      most important problems of contemporary health service. Since 1985 and
      particularly in the 1990s and at present the search for new structures of
      antimycobacterial agents have ranked among the foremost areas of chemotherapeutic
      research. The present review paper is already the 17th communication in a group
      of review papers about the development of new antituberculotics, the sixth about
      the development in recent 15 years and the second communication devoted in this
      series to ortho-condensed heterocyclic compounds. The classification of ortho
      condensed compounds is based on six-membered heterocyclic substructural
      fragments. The literature search is based on the journal Chemical Abstracts,
      Current Awareness in Biomedicine, part Mycobacteria, and original papers. Current
      Awareness in Biomedicine is, however, a very imperfect literature search source,
      recording only a fraction of communications.

PMID- 11579687
TI  - [Phytotherapeutic aspects of diseases of the circulatory system. 8. Chinese
      magnolia (Schisandra chinensis (Turcz.) Baill.): production of the drugs and
      their evaluation, therapeutic and dietary preparations].
AB  - Extracts from the fruits (seeds) of Schisandra chinensis L. and pure isolated
      substances are one of the components of medicinal preparations designed for the
      treatment of cardiovascular diseases, liver diseases, diseases of the CNS related
      to the old age, as a supplement in the treatment of neoplasms, diabetes, etc.
      They are also used for the production of nutraceuticals (soft drinks and health
      foods), preparations for oral hygiene and for the care for the skin and hair. The
      review discusses complex analytical methods used for the determination of the
      content of substances and the phenomena of population ecology in relation with
      drug production.

PMID- 11579688
TI  - [Biochemical and molecular biology aspects of plant phospholipase D].
AB  - Phospholipase D (PLD) was first discovered in plants. It plays an important role
      in the regulation of cell functions not only in plants, but also in animal
      systems. It is interesting from the aspect of its dominant position in the
      signalling transduction processes. It controls the utilization of the membrane
      phospholipids for specific intentions--products of its catalytic activity are
      involved in intracellular communication processes. The study of the cell
      regulation-system shows that PLD is a part of lipid-based signalling via
      octadecanoid pathway, which leads to the production of jasmonic acid, the basic
      signalling molecule in plants. PLD-mediated hydrolysis of the membrane
      phospholipids posed this enzyme into the level of the transmembrane and cell
      signalling participant. This area is interesting in the aspect of the production
      of biologically active compounds in plants. Because the signal-regulated
      synthesis of some secondary metabolites by the lipid signalling pathway has been
      already shown (induction of the gene expression coding the biosynthetic enzymes
      of flavonoids and terpenoids), the area of PLD study is perspective. This article
      is orientated on plant PLD and gives a basic review of its biochemical and
      molecular-biological properties (enzymology, molecular structure, subcellular
      localization, isoenzymes) and its physiological functions on the cell level
      (lipid signalling pathway, phospholipid degradation, phytohormones and cell
      signalling, growth, development and cell ageing, membrane remodeling).

PMID- 11579685
TI  - Familial nonmedullary thyroid neoplasia.
AB  - Thyroid carcinoma accounts for less than 1% of all human malignancies and carries
      one of the highest overall familial relative risks as compared with cancers from
      other sites. This is particularly true for medullary carcinoma, as well as for
      carcinomas of follicular cell origin in general, where inheritance has been
      implicated in 2.5 to 6.3% of the cases. Familial nonmedullary thyroid tumors show
      a variety of genetic mechanisms implicated in thyroid tumorigenesis and occur in
      several tumor-prone traits (e.g., familial adenomatous polyposis [FAP] and
      Cowden's disease [CD]) or as the only or dominant inherited manifestation. The
      latter group includes the most common familial papillary carcinoma, in which
      environmental factors such as radiation exposure may also play an important
      etiological role. Familial follicular cell tumors show a variety of morphological
      features ranging from benign thyroid nodulation to carcinoma, usually develop in
      young individuals, and tend to be multicentric--an indication for total
      thyroidectomy to avoid tumor recurrence and potential risk of malignant
      transformation. The pathologist may play an important role in the histological
      interpretation of familial nonmedullary thyroid tumors, which may lead to further
      clinicogenetical investigations of the affected patient and family screening.
      Familial follicular cell thyroid neoplasms show a complex molecular biological
      pathway of tumorigenesis when compared between themselves and with their sporadic
      counterparts.

PMID- 11579689
TI  - [Study of local anesthetics. CLVII. Chromatographic properties of pentacaine,
      carbisocaine, heptacaine and its 3-, and 4-positional isomers in the RP HPLC
      system].
AB  - The present study aimed to find a suitable HPLC system for the determination of
      the values of the capacity factor of k' pentacaine, carbisocaine, heptacaine, and
      its 3-, and 4-positional isomers. The column Separon SG X C-18 and a mobile phase
      consisting of 90% methanol and 10% water (with 0.5 mol/l of sodium acetate) were
      demonstrated to be suitable for the separation of these potential local
      anaesthetics from the group of phenylcarbamic acid derivatives. In this system,
      k'o for pentacaine is 22.9, for carbisocaine 8.6, for heptacaine 8.1, and for 3
      positional derivative of heptacaine, 13.0, and 4-isomer, 18.4. It results from
      the data that log k' of these drugs is in the interval 2-5 and even minor changes
      in the concentration of sodium acetate (c = 0.5 +/- 0.05 mol/l) do not change it
      markedly.

PMID- 11579690
TI  - [Cytotoxic and genotoxic activity of certain preservative agents in cosmetics].
AB  - Cytotoxic effects of the preservative compounds for cosmetics JMAC TD, Bronopol,
      CA 24, and Euxyl K100 were studied. Bronopol demonstrated the highest cytotoxic
      effect on the proliferation of V79 and VH10 fibroblast cell lines--the IC100
      values being 10 mg/l during the whole experiment. The preservatives CA 24 and
      Euxyl K100 showed 4-times and 5-times smaller cytotoxic activity than Bronopol
      IC100 = 42 or 50.3 mg/l). The preservative compounds on silver chloride ions JMAC
      TD manifested the lowest cytotoxicity of the preservatives tested (IC100 = 150
      mg/l); 15-times smaller than Bronopol, 3.5-times smaller than CA 24 and 3-times
      smaller than Euxyl K100. The biocide JMAC TD did not exhibit mutagenic effects on
      the bacteria Salmonella typhimurium TA 98 and TA 100.

PMID- 11579691
TI  - [Unused drugs returned to pharmacies. II].
AB  - The problems related to unused drugs kept in households and returned to
      pharmacies have been investigated from various viewpoints. After an analysis of
      preparations which had both the primary and secondary container, or only the
      primary one (set I), sets II (free blisters and strips), III (free solid dosage
      forms which occurred singly) IV (extemporaneously prepared medicinal
      preparations), and V (health service appliances) were analyzed. Out of set II
      (1,233 blisters), 274 (22.2%) were used and 959 (77.8%) were still complete,
      unused. The expiration period was over in 66.1% of blisters, 29.8% was still
      usable, and in 4.1% of blisters the expiration period could not be determined.
      The value of returned drugs was 185,287 Czech crowns, after conversion it was
      61,762 Czech crowns.

PMID- 11579692
TI  - [Effect of chitosan on the production of anthracene derivatives in tissue culture
      of Rheum palmatum L].
AB  - Explant cultures have been, besides other things, used for elicitation, which is
      an economically advantageous method making use of protective mechanism of plants
      to increase the production of secondary metabolites. The present study
      investigated the effect of 6, 12, 24, 48, 72, and 168 hours lasting action of
      four concentrations of the biotic elicitor chitosan on the production of
      anthracene derivatives by the callus and suspension culture of Rheum palmatum L.
      The culture was cultivated on a Murashige-Skoog medium with an addition of 10
      mg.l-1 of alpha-naphthylacetic acid. A positive effect on the production was
      exerted in particular by elication of the suspension culture. The maximal content
      of anthracene derivatives (1.181%), found by photometric determination according
      to PhBs 4, as demonstrated after 24-hour action of a chitosan solution of a
      concentration of 1 mg/30 ml of the medium. In contrast to the suspension culture,
      the production of anthracene derivatives in the callus culture was influenced by
      elicitation only in the minimal way.

PMID- 11579693
TI  - [Effect of diazepam on antidote therapy of lethal toxic effects of soman in
      rats].
AB  - Experiments on male rats examined the effect of a basic antidotal therapy
      consisting of various types of anticholinergic substances and reactivators of
      acetylcholinesterase on the lethal effects of the highly toxic organophosphorous
      compound soman by means of determination of the medium lethal dose of soman in 24
      hour survival of experimental animals. The efficacy of the basic antidotal
      therapy of acute intoxications by soman evaluated in this way was compared with
      the effect of an antidotal therapy enriched with diazepam, a drug with
      anticonvulsive action. The obtained results show that addition of diazepam to the
      basic antidotal therapy increases the ability of the antidotal therapy to
      eliminate acute lethal effects of soman if it includes atropine as an
      anticholinergic agent regardless of the employed type of acetylcholinesterase
      reactivator. In the case of employment of anticholinergic agents with prevailing
      central effects, such as benactyzine, biperiden, or scopolamine, the addition of
      diazepam will not significantly influence the therapeutic efficacy of the
      antidotal therapy regardless of the selected aetylcholinesterase reactivator. At
      the same time, the addition of diazepam to the antidotal therapy does not change
      the difference in the efficacy of the antidotal therapy in dependence on the
      selected anticholinergic agent or acetylcholinesterase reactivator. At present
      the most common combination of antidotes against soman, consisting of obidoxime
      and atropine, as well as a prospective combination containing oxime HI-6 and
      atropine should be supplemented with diazepam not only to prevent centrally
      induced seizures and tonic-clonic convulsions but also to increase the ability of
      such antidotal therapy to eliminate acute lethal toxicity of soman.

PMID- 11579694
TI  - Influence of landing on the supination and pronation in the foot joint.
AB  - The purpose of this study was to measure the changes of supination and pronation
      in the ankle joint at landing to quantify the influence of shock attenuation
      during landing. The subjects did two different motions, jumping down on the force
      platform from posterior and lateral views. The rear view of single foot contact
      in a jump from height of 30 and 60 cm showed a landing on the inside of the rear
      part of the foot (pronation) followed after about 0.03 sec by a rolling outward
      of the foot (supination). The variables describing changes in three angles of the
      ankle joint indicated that the standing position was more sensitive on the
      pronation and supination during ground contact.

PMID- 11579695
TI  - Occupational workload of fisherwomen in India.
AB  - A group of 60 fisherwomen, aged 20 to 50 yrs., were studied to evaluate their
      occupational workloads. Of the eight activities involved in fish handling, only
      four, viz., sorting, washing, drying, and selling, which are most frequently
      carried out by the fisherwomen, were selected. The heart rate responses and
      rating of perceived exertion (RPE) were used as measures of occupational
      workload. Based on the findings, the occupational workload could be classified as
      "moderately heavy". A significant influence of age and body weight on the
      physiological workload was observed, being negatively correlated with age and
      positively with weight.

PMID- 11579696
TI  - Effects of an artificially carbonated bath on athletic warm-up.
AB  - The effects of an artificially carbonated bath (36 degrees C, CO2 300 ppm, 20
      minutes) on the warm-up of swimmers was compared with those of a freshwater bath
      (36 degrees C, 20 minutes). Carbon dioxide is reported to have a vasodilatory
      effect on peripheral blood vessels of cutaneous and muscular tissue and to
      promote blood flow. We observed that the warm-up effects of a carbonated bath
      before swimming on the hematocrit, white blood cell, total plasma protein, and
      total cholesterol levels in venous blood were significantly increased more than
      those of a freshwater bath before swimming in recovery period (p < 0.05). Thus
      the carbonated bath tended to be more effective for increasing the concentrations
      of blood components. In the recovery period, the carbonated bath before swimming
      also resulted in significantly smaller changes in blood lactic acid and heart
      rate than those of a freshwater bath before swimming (p < 0.05). The decrease in
      electromyography of the M. rectus femoris during swimming suggested more
      efficient muscle activity after a carbonated bath. Therefore after a carbonated
      bath, swimmers should have a higher reserve left in the cardiovascular system,
      resulting in better performance during swimming and less accumulation of fatigue
      related metabolites after swimming.

PMID- 11579697
TI  - Influence of music on heart rate variability and comfort--a consideration through
      comparison of music and noise.
AB  - By considering three kinds of music and noise, this research investigates the
      influence of music on the living body by comparing the difference of influence on
      heart rate variability and comfort when subjects listen to music and are exposed
      to noise. We used two pieces of classical music, rock music, and noise recorded
      by a tape recorder. The following conclusions were made from the findings of the
      research: 1) Hearing classical music results in a small variance of Mayer Wave
      related Sinus Arrhythmia (MWSA) component and Respiratory Sinus Arrhythmia (RSA)
      component compared with a body being at rest. This is because the sympathetic
      nerve is suppressed by the sound of classical music. With rock music and noise,
      however, the MWSA component increases and the RSA component decreases. 2) From a
      psychological evaluation, we found that classical music tends to cause comfort
      and rock music and noise tend to cause discomfort. 3) A correlation was found
      between the balance of the MWSA component and the RSA component and the
      psychological evaluation. As the comfort increases, the variance of MWSA
      decreases; as discomfort increases, the variance of MWSA increases.

PMID- 11579698
TI  - How is a seita fitted to the body?
AB  - A seita is a carrier frame for backpacking used in Nishiki-cho, Yamaguchi
      Prefecture, Japan. In this mountainous district, people make their living by
      agriculture and forestry and carry everything on their backs with seita. In this
      study, we investigated the relationships between the sizes of a body and the
      dimensions of a seita. This survey was conducted on 30 subjects (mean +/- SD;
      68.1 +/- 9.0 years old) at three mountain villages. We measured some
      anthropometric sizes and seita dimensions and found that the correlation between
      height and sum of shoulder-lumbar-nuki distance (back length of a seita) and
      shoulder strap length is significant. In additional surveys, we took photographs
      with some markers on iliocristale, trochanterion, and so on, when the subjects
      carried seita in two load conditions. The photographs indicate that the load
      supporting points in 16 of 23 subjects were between the iliocristale and
      trochanterion (i.e., on the sacrum). It is important to note that nobody showed
      that point above the iliocristale (i.e., on the lumbar vertebra). These data lead
      to the conclusion that when people in Nishik-icho carry loads with seita, they
      support loads not on the lumbar vertebrae but on the sacrum, and that they adjust
      the perimeter consisting of the back part and shoulder strap of the seita.

PMID- 11579699
TI  - Experimental study of seita-fitting.
AB  - The purpose of this study was to verify the difference between carrying a load on
      the sacrum (LOS) and on the lumbar vertebrae (LOL) in oxygen uptake, muscle
      activities, heart rate, cadence, and subjective response. Nine males (26.7 +/-
      3.1 years old), each carrying a 7.5 kg carrier frame and a 40 kg load, walked on
      a treadmill at a speed of 50 m/min. EMGs were recorded from the trapezius, rectus
      abdominis, erector spinae, vastus lateralis, rectus femoris, vastus medialis,
      biceps femoris long head, tibial anterior, soleus, medial head of gastrocnemius,
      and the lateral head of gastrocnemius. For each subject the integrated EMG (IEMG)
      was normalized by dividing the IEMG in the LOL and LOS by the IEMG in a no-load
      condition (NL) for each investigated muscle. The following was significantly
      higher in LOL than in LOS: oxygen uptake; IEMG of the tibial anterior, soleus,
      and medial head of gastrocnemius; cadence; and rated perceived exertion. However,
      IEMG of the erector spinae was significantly lower in LOL than in LOS. These
      results suggest that seita-fitting in LOS causes a decrease of leg muscle
      activities, which causes oxygen uptake to decrease beyond the increase of the
      erector spinae activity.

PMID- 11579700
TI  - Lifting patients in bed with and without a drawsheet: a comparative ergonomics
      study.
AB  - Two techniques for lifting a patient in bed, namely with and without the use of a
      drawsheet, have been compared from an ergonomics point of view. Forty-two nurses
      of a Thai university hospital were studied before and after using each method by
      measuring back strengths and by using a questionnaire for feelings of fatigue and
      for musculoskeletal fatigue and pain. Decreases in back strength 10 minutes after
      and immediately after lifting with each method were found to be significant (90%
      confidence). The decrease 10 minutes after lifting was found to be significantly
      smaller with a drawsheet than without one (98% confidence). Immediately after
      lifting there was less difference between the two methods, which indicates that
      the use of a drawsheet reduced the recovery time and the decrease in back
      strength. Increases in feelings of fatigue from lifting with each method were
      also found to be significant (90% confidence), and the results indicate that the
      increase was lower with a drawsheet than without one. Musculoskeletal fatigue and
      pain immediately after lifting were more common without a drawsheet than with
      one. In conclusion, the lifting technique with a drawsheet is ergonomically
      superior and should be used by nursing personnel.

PMID- 11579702
TI  - Factors contributing to discomfort or dissatisfaction as a result of wearing
      personal protective equipment.
AB  - In a metal refining plant, 366 workers were interviewed to investigate factors
      contributing to the discomfort or dissatisfaction of wearing personal protective
      equipment (PPE). Up to 97.8% of these individuals used one or more types of PPE.
      The percentages of employees who reported their hard hats and cooling vests as
      comfortable were 17% and 19%, respectively. Twenty-five percent of workers felt
      their respirators and safety harnesses were comfortable. Safety glasses ranked at
      50%, gloves 53%, and safety shoes 54% for comfort factor. The percentage of
      employees who tolerated their PPE (just acceptable) ranged from 27% to 52%. The
      most frequently cited factors contributing to discomfort or dissatisfaction of
      wearing PPE were related to the workers' beliefs that the PPE was not needed,
      created a new hazard, interfered with work, was too heavy, was hard to wear,
      prohibited breathing or communicating, irritated skin, put pressure on the body,
      and was of an undesirable type or model.

PMID- 11579701
TI  - Influence of VDT monitor positions on discomfort and performance of users with or
      without bifocal lenses.
AB  - The difficulty of video display terminal users with bifocal lenses through a
      traditional workstation increases the complaints and risks for upper extremity
      cumulative trauma disorders. Furthermore, the regular and no lens users also have
      problems with traditionally designed workstations over prolonged periods of video
      display terminal use. A study was conducted on 14 subjects to investigate the
      effect of computer monitor location for video display terminal users with or
      without bifocals on subjective assessment and performance. The two monitor
      locations were 15 degrees and 40 degrees below horizontal eye level. The
      experimental task consisted of reading words from computer screens and typing
      them from the reverse side to the next column. Each experimental session lasted
      one hour. Males with bifocal lenses had less discomfort in the neck, shoulders,
      forearms, and wrists, less tiredness and eyestrain and higher performance with a
      40 degrees angle monitor than with a 15 degrees angle monitor. A similar
      conclusion has been reached for females. Users with bifocal lenses had
      significantly higher neck discomfort and lower performance than nonbifocal users.
      The 40 degrees angle monitor caused less neck discomfort than the 15 degrees
      angle monitor did. Overall, females had less physical discomfort, less tiredness,
      and higher performance than males.

PMID- 11579703
TI  - The female/male ratio of anthropometric dimensions.
AB  - A great many anthropometric studies contain the data of either males or females.
      Instead of presenting single-sex data, this study presents a method of using the
      female/male (F/M) ratio to estimate the dimensions of unknown body parts. Several
      studies that include the data for both sexes are used to develop the ratio.
      Statistical analysis is performed, including fitting to normal distribution.
      Stature, sitting shoulder height, shoulder breadth, and hip breadth are used in
      the study. The result of the analysis reveals the importance of using a different
      F/M ratio for each body part instead of adopting a single value for estimation.

PMID- 11579705
TI  - Cyclophosphamide therapy induces ovarian failure in premenopausal women affected
      by systemic lupus erythematosus.

PMID- 11579704
TI  - Modern treatment of childhood SLE.

PMID- 11579706
TI  - Modification of DNA patterns in plasma and nucleated blood cells from systemic
      sclerosis patients.
AB  - OBJECTIVE: To analyze the DNA patterns extracted from plasma and nucleated blood
      cells (lymphocytes) in systemic sclerosis (SSc) with a new MFC DNA extracting
      kit. METHODS: Ten SSc patients and 9 healthy controls were studied. Heparin
      containing blood samples were separated into plasma and buffy coat fractions and
      subjected to DNA extraction. The DNA pattern was revealed by 0.4% agarose
      electrophoresis and analyzed in a Gelblot Programme file (UVP Product). RESULTS:
      In control samples the DNA pattern observed in plasma extract was different from
      that of the buffy coat. For the plasma a series of peaks ranging from 2-23 Kb
      were present, and for the buffy coat we usually observed 2 to 3 principle bands,
      respectively, at around 33 Kb and 0.5 Kb. For SSc patients the DNA patterns that
      resulted from the plasma and buffy coat were totally different from the control
      samples, with some exceptions. CONCLUSION: We observed that SSc samples contain a
      distinctively different DNA pattern compared to healthy controls. Further studies
      are needed to establish whether or not this DNA pattern might be considered
      peculiar to SSc, and whether or not the method is a useful tool for pathogenic
      studies of the disease and for diagnostic purposes.

PMID- 11579707
TI  - A prospective, double-blind, randomized, placebo controlled trial of methotrexate
      in the treatment of giant cell arteritis (GCA).
AB  - OBJECTIVE: To determine if methotrexate has disease-controlling and
      corticosteroid (cs)-sparing effects in the treatment of giant cell arteritis
      (GCA). METHODS: This was a randomized, controlled, double-blind trial comparing
      methotrexate versus placebo in addition to corticosteroid therapy in patients
      with newly diagnosed giant cell arteritis. Patients with giant cell arteritis
      were enrolled and treated with high dose corticosteroids as well as methotrexate
      starting at 7.5 mg/week or placebo. Corticosteroids were tapered by the treating
      physician as guided by the clinical picture, with methotrexate or placebo dose
      increased by 2.5 mg/week for disease flare with a maximum allowable dose of 20
      mg/week. After a clinically-defined remission and steroid discontinuation,
      methotrexate or placebo was tapered monthly to zero by 2.5 mg/week. RESULTS:
      Twenty-one patients were enrolled, 12 randomized to methotrexate, 9 to placebo.
      Baseline characteristics (age, height, weight, sedimentation rate, bone mineral
      density, total corticosteroid dose prior to randomization, and quality of life as
      measured by SF-36 and function as measured by AIMS) were comparable between
      groups. At completion, there was no significant difference between methotrexate-
      and placebo-treated patients with regard to the cumulative corticosteroid dose
      (6469 mg and 5908 mg respectively, p = 0.6), number of weeks to completion of
      steroids (68 and 60 respectively, p = 0.5), time (weeks) to taper prednisone to
      less than 10 mg prednisone/day (23 and 25 respectively, p = 0.5), bone mineral
      density in lumbar spine (p = 0.2) or hip (p = 0.4) at one year, or functional
      status as measured by AIMS and quality of life as measured by SF36. There was no
      late vision loss in either group, and only one major treatment-responsive relapse
      in a methotrexate-treated patient. There were few major corticosteroid-related
      side effects and these did not significantly differ between groups. CONCLUSION:
      With this study design, no corticosteroid-sparing benefit could be attributed to
      the combination of methotrexate with corticosteroid therapy for the treatment of
      patients with giant cell arteritis. Both groups did well, with few major
      corticosteroid-related side effects, and most patients were safely tapered off
      corticosteroids sooner than reported in many series. The shorter overall duration
      of steroid treatment in this study probably contributed to the remarkably low
      frequency of side effects, without increased ischemic risk for the patient.

PMID- 11579708
TI  - Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's
      phenomenon. A randomized, controlled study.
AB  - OBJECTIVE: Iloprost is a stable prostacyclin analogue which has been shown to be
      effective in the short-term symptomatic treatment of Raynaud's phenomenon (RP)
      secondary to systemic sclerosis (SSc). The aim of this study was to evaluate the
      effects of long-term cyclic therapy with iloprost in comparison with nifedipine
      on the skin score, pulmonary function and Raynaud's severity score in patients
      with SSc and RP. METHODS: We conducted a 12-month prospective, randomised,
      parallel-group, blind-observer trial to compare the effects of intravenously
      infused iloprost (2 ng/kg/min on 5 consecutive days over a period of 8 hours/day
      and subsequently for 8 hours on one day every 6 weeks) with those of conventional
      vasodilating therapy with nifedipine (40 mg/day for os) in 46 patients with SSc
      and RP. RESULTS: At 12 months, iloprost but not nifedipine reduced the skin score
      (iloprost: from 13.26 +/- 2.05 to 9.26 +/- 1.32, p = 0.002; nifedipine: from
      10.83 +/- 2.09 to 12.17 +/- 3.02, p = n.s.; iloprost vs nifedipine: p = 0.016)
      and the RP severity score (iloprost: from 2.17 +/- 0.2 to 1.22 +/- 0.13, p = 0.02
      vs baseline; nifedipine: from 2.08 +/- 0.34 to 1.33 +/- 0.22, p = n.s.). Carbon
      monoxide diffusing capacity (DLCO), expressed as % of the predicted normal value,
      worsened significantly in the nifedipine group (from 69.6 +/- 7.4% to 61.5 +/-
      6.5%, p = 0.044) and remained stable in patients treated with iloprost (from 53.2
      +/- 4.8 to 56.0 +/- 4.6%, iloprost vs nifedipine: p = 0.026). CONCLUSION: In SSc
      patients, cyclic intravenous iloprost infusion is able to control vasospastic
      disease. Our results suggest that it might also act as a disease-modifying agent,
      as it seems to improve the course of the disease. Further studies principally
      focused on organ involvement and the natural history of the disease are needed to
      confirm our results.

PMID- 11579709
TI  - Sleep disturbances in patients with systemic lupus erythematosus: a questionnaire
      based study.
AB  - OBJECTIVE: To assess the prevalence of subjective sleeping complaints by patients
      with systemic lupus erythematosus (SLE) and to evaluate the correlation between
      various sleeping complaints and disease activity. METHODS: A standardised sleep
      questionnaire, The Uppsala Sleep Inventory, was used to investigate the sleeping
      habits of 30 outpatients with systemic lupus erythematosus (SLE) in comparison to
      population-based age- and sex-matched controls. RESULTS: Sleep deficit
      (difference between need of sleep and actual sleeping time) was similar in
      patients with SLE (0.8 +/- 0.9 hour) and age-matched female controls (0.4 +/- 0.8
      hour). However, patients with SLE reported more frequent disturbances due to
      pain, both when trying to fall asleep (p < 0.01) and during the night (p < 0.01).
      They also reported frequent awakenings due to headache (p < 0.01) and
      disturbances due to other vegetative symptoms. Furthermore, the SLE patients were
      awake for significantly longer periods during the night and they estimated their
      degree of fatigue as significantly higher than the female controls (p < 0.0001).
      CONCLUSION: Patients with SLE seem to get a fairly normal amount of sleep, but
      are frequently disturbed by pain and by various vegetative symptoms, e.g.
      breathlessness, sweating, and palpitation, which indicate not only pain but also
      possible involvement of the nervous system. The nervous system may therefore play
      a role in sleep disturbances reported by patients with SLE.

PMID- 11579710
TI  - Serum and in vitro production of IL-1 receptor antagonist correlate with C
      reactive protein levels in newly diagnosed, untreated lupus patients.
AB  - OBJECTIVE: To examine the correlation between C-reactive protein (CRP) and CRP
      inducing cytokines (IL-1 beta, IL-6, TNF-alpha) and IL-1 receptor antagonist (IL
      1ra), as well as to study their relationship with systemic lupus erythematosus
      disease activity (SLEDAI) in newly diagnosed, untreated lupus patients. METHODS:
      Sera from newly diagnosed untreated lupus and rheumatoid arthritis (RA) patients
      were examined for CRP and cytokines. Data were compared among patient groups and
      correlated individually among the lupus group. Lupus monocytes and neutrophils
      were cultured in vitro to produce IL-1ra and experimental results were related to
      CRP levels and SLEDAI. RESULTS: Within lupus, serum CRP, IL-6, IL-1 beta and TNF
      alpha levels were significantly lower than those of RA (all p values were <
      0.005) and generally higher than those in the controls (p = 0.002, < 0.001, >
      0.2, and < 0.001, respectively). Except IL-1ra, which was correlated with CRP (p
      = 0.045), no substantial correlation was discovered between CRP and IL-6, IL-1
      beta or TNF-alpha individually. Moreover, excluding IL-1ra (p = 0.024), there was
      no association between cytokines and SLEDAI. In vitro IL-1ra as secreted by
      monocytes correlated with serum CRP and SLEDAI. CONCLUSION: In lupus patients,
      serum IL-1 beta, IL-6 or TNF-alpha levels failed to correlate with low CRP
      levels. This indicates a complicated CRP production process, which can not be
      explained solely by single cytokines as reported previously. Both serum and in
      vitro produced IL-1ra may be applied clinically as a surrogate CRP marker in
      untreated lupus patients as they are both correlated with serum CRP.

PMID- 11579711
TI  - Long-term effects of osteogenic protein-1 on biosynthesis and proliferation of
      human articular chondrocytes.
AB  - OBJECTIVE: To study the long-term effects of OP-1 on the biosynthesis and
      proliferation of human articular chondrocytes. METHODS: Chondrocytes were
      released from human cartilage from 10 organ donors of different ages and cultured
      in alginate. They were exposed to OP-1 (0-200 ng/ml) for 3 to 60 days.
      Proteoglycan (35S-sulfate) and collagen (3H-proline) synthesis were measured by
      radiolabeling. Proteoglycan content was determined by a dimethylmethylenblue
      assay, hydroxyproline content by a colorimetric assay, and DNA content by a
      fluorometric assay. RESULTS: Long-term (60 days) cultures of human adult
      articular chondrocytes stimulated by OP-1 (50 ng/ml) revealed a relative decrease
      of proteoglycan and collagen synthesis. However, proteoglycan (5-fold) and
      collagen (1.4-fold) content were increased even after 60 days in culture when
      compared to controls. Maintaining the chondrocyte phenotype (aggrecan synthesis
      as the main proteoglycan) in long-term culture, OP-1 (50 ng/ml) stimulated
      proliferation up to 2.4-fold. CONCLUSION: Maintaining a stable phenotype and
      accelerating matrix assembly and proliferation in long-term culture OP-1 might
      support the tissue engineering of human cartilage.

PMID- 11579712
TI  - A sensitive assay for the measurement of serum chondroitin sulfate 3B3(-) epitope
      levels in human rheumatic diseases.
AB  - OBJECTIVE: To develop a sensitive assay to quantitate serum 3B3(-) levels in
      patients with rheumatoid arthritis (RA) and osteoarthritis (OA) as well as levels
      in control sera. METHODS: An enzyme-linked immunosorbent assay (ELISA) was
      developed using the monoclonal antibody (MAb) 3B3 to detect a chondroitin sulfate
      (CS) epitope in the sera and synovial fluid (SF) of RA and OA patients. Keratan
      sulfate levels were measured in the same biological fluids using the 5D4
      monoclonal antibody. RESULTS: The detection limit for our 3B3(-) assay was 2
      micrograms/L. Most OA sera sample curves run on the 3B3 assay were parallel
      (87.5%) to the standard curve and detectable (90.0%). RA sera sample curves were
      87.1% detectable and 85.2% parallel. The 3B3(-) epitope was detectable in 60% of
      control sera and of these 66.7% of sample curves were parallel to the standard
      curve. All RA and OA SF had detectable quantities of 3B3(-). For the 3B3 assay,
      the OA and RA sera levels were significantly higher than for control sera (P =
      0.03, P = 0.04 respectively). We found a significant correlation in a subset of
      paired OA sera and SF 3B3(-) concentrations. No correlation was found between
      age, joint activity scores, HAQ and CRP in RA patients and sera 3B3(-) and 5D4
      levels. CONCLUSION: We have validated this assay for the quantification of 3B3(-)
      epitope in RA and OA serum. Levels of this epitope are significantly higher in
      sera from RA and OA patients than controls. 3B3(-) levels in RA sera were found
      to correlate with disease duration.

PMID- 11579713
TI  - Severe CNS manifestations as the clinical hallmark in generalized Wegener's
      granulomatosis consistently negative for antineutrophil cytoplasmic antibodies
      (ANCA). A report of 3 cases and a review of the literature.
AB  - OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) directed against
      proteinase 3 are highly specific for Wegener's granulomatosis (WG); their
      sensitivity for active generalized WG is nearly 100%. There are patients,
      however, who fulfill both the ACR 1990 criteria and the CHC 1992 definition for
      WG but who remain ANCA negative. The authors report 3 young patients with biopsy
      proven active generalized WG who were consistently negative for ANCA over
      observation times ranging from 58 to 114 months. METHODS: ANCA titers were
      determined serially every 3 months. ANCA-negativity was defined by the absence of
      any fluorescence pattern on IFT plus the absence of any specific ELISA reactions.
      This included negative results for the antibody classes IgG, IgM and IgA. The
      sera of all patients were also tested in a capture PR3-ANCA ELISA. At 1- to 6
      month intervals each patient underwent a standardized set of interdisciplinary
      examinations. RESULTS: Although CNS involvement in large WG cohorts is about 10%,
      severe CNS manifestations were the clinical hallmark in all 3 patients. One
      patient suffered from both intraspinal and intracerebral disease with fatal
      outcome; the other 2 had meningeal manifestations that responded favorably to
      immunosuppressive therapy. CONCLUSION: Severe CNS manifestations could represent
      a clinical hallmark of patients with generalized Wegener's granulomatosis who are
      consistently negative for antineutrophil cytoplasmic antibodies (ANCA).

PMID- 11579715
TI  - Subcutaneous calcification on the nose in a patient with scleroderma.

PMID- 11579714
TI  - Subclinical pulmonary involvement assessed by bronchoalveolar lavage in patients
      with early undifferentiated connective tissue disease.
AB  - OBJECTIVE: To assess the presence of neutrophil and lymphocyte fibrosing
      alveolitis by bronchoalveolar lavage in patients with early undifferentiated
      connective tissue disease (EUCTD) and systemic sclerosis (SSc). METHOD:
      Bronchoalveolar lavage (BAL) was performed in 13 patients with EUCTD who
      exhibited signs of lung involvement by non-invasive methods including lung
      function tests and high resolution computed tomography. The mean age of cases was
      48.1 +/- 6.6, and the mean disease duration was 1.8 +/- 0.8 years. Differential
      cell counts of BAL were evaluated. Eleven patients with systemic sclerosis and 5
      healthy control subjects were also investigated. RESULTS: Eleven of the 13 EUCTD
      and 10 of the 11 SSc patients showed an elevated total cell number (above the
      median cell/ml of control + 2 SD) in the BAL fluid. In patients with EUCTD, the
      lymphocyte count was elevated in 6, and the polymorphonuclear neutrophil count in
      2 patients. One of the patients with EUCTD had simultaneously elevated lymphocyte
      and neutrophil granulocyte counts. In the SSc group, 6 patients had an elevated
      lymphocyte and 6 an increased neutrophil count. Three of these cases had both
      increased neutrophil and elevated lymphocyte counts, simultaneously. CONCLUSION:
      Subclinical, predominantly lymphocyte alveolitis can be present in patients with
      EUCTD. Patients with SSc tend to exhibit neutrophil alveolitis.

PMID- 11579716
TI  - Homocysteine and antiphospholipid antibodies in rheumatoid arthritis patients:
      relationships with thrombotic events.
AB  - OBJECTIVE: To investigate the possible relationships between plasma homocysteine
      levels and thrombotic events in a select population of rheumatoid arthritis (RA)
      patients with or without antiphospholipid (aPL) antibody positivity. METHODS: 168
      female RA patients attending the Extra-articular Involvement RA Clinic of
      University of Genova and 72 female subjects matched for age and vascular diseases
      as controls were included in the study. 30 of the RA patients showed aPL antibody
      positivity and 138 aPL antibody negativity on the basis of the concomitant
      presence or absence of high concentrations of anticardiolipin (aCL) antibodies or
      the presence of lupus anticoagulant (LA). All subjects were evaluated for plasma
      homocysteine concentrations and for the occurrence of thrombotic events. RESULTS:
      Twenty-five RA patients and 5 controls reported a history of thrombotic events.
      Eleven and 5 of RA patients were found to have been previously affected by venous
      or arterial thrombosis, respectively. Plasma levels of homocysteine in aPL
      antibody positive patients with thrombosis were found to be significantly higher
      than in aPL antibody positive RA patients without thrombosis (p < 0.001). When RA
      patients with thromboses were analyzed, a significant increase of plasma
      homocysteine levels was found in aPL antibody-positive RA patients versus aPL
      antibody-negative RA patients (p < 0.04) and versus related controls (p < 0.003).
      CONCLUSIONS: The association observed between aPL antibody positivity and high
      levels of plasma homocysteine in RA patients may represent a possible risk factor
      for thrombotic events. Therefore, it is suggested that hyperhomocysteinemia might
      be involved in the vascular-related mortality observed in RA patients with a
      history of thrombosis.

PMID- 11579717
TI  - Calcification of the internal elastic membrane in temporal arteries: its relation
      to age and gender.
AB  - OBJECTIVE: To investigate the age and sex distribution of calcifications of the
      internal elastic membrane (IEM) in temporal arteries. METHODS: Calcifications of
      the IEM were assessed light-microscopically in temporal arteries from 40 women
      and 21 men, aged 51 or more, who were known not to have giant cell arteritis
      (GCA). Their relation to age and the difference between women and men were tested
      statistically. RESULTS: The IEM calcifications differed morphologically from the
      calcifications in Monckeberg's mediosclerosis and atherosclerosis. They increased
      significantly with age and were 2.62 times more common in women than men.
      CONCLUSION: Previous morphological studies indicate that the inflammatory process
      in GCA is initiated by a foreign-body, giant-cell attack on calcifications of the
      IEM. The present study showed that IEM calcifications in non-GCA controls show an
      age and sex distribution similar to that of GCA morbidity. The results may
      indicate that the presence of IEM calcifications in the general population
      influences the age and sex distribution of GCA. Furthermore, the findings support
      the hypothesis that the calcifications, although not disease specific, may play a
      pathogenetic role in the latter.

PMID- 11579718
TI  - Asymptomatic gastrocnemius muscle biopsy: an extremely sensitive and specific
      test in the pathologic confirmation of sarcoidosis presenting with hilar
      adenopathy.
AB  - OBJECTIVE: To evaluate asymptomatic gastrocnemius muscle biopsy as a tool in the
      histologic confirmation of the diagnosis of sarcoidosis. METHODS: Twenty-two
      patients admitted over a 2-year period to our department with bilateral hilar
      adenopathy and a variety of symptoms compatible with sarcoidosis were studied
      prospectively. Besides a complete history and physical, serum angiotensin
      converting enzyme (SACE) determination, pulmonary function, slit lamp eye
      examination, PPD skin test, gallium 67 scan and gastrocnemius muscle biopsy were
      performed. RESULTS: The biopsy revealed non-caseating granuloma in all patients,
      confirming the diagnosis of sarcoidosis. No other patient in our department
      received this diagnosis over the 2-year period of the study. The procedure was
      well tolerated by all patients and almost zero morbidity was noted. Erythema
      nodosum was present in 68.2% of the patients, PPD was negative in all of them,
      SACE was elevated in 59.1% and pulmonary function was normal in the majority.
      CONCLUSION: The impressive sensitivity of asymptomatic gastrocnemius muscle
      biopsy, its safety and ease of performance, along with the extreme rarity of
      muscle involvement by other granulomatous diseases included in the differential
      diagnosis, may render it the procedure of choice for the histologic confirmation
      of sarcoidosis presenting with hilar adenopathy.

PMID- 11579719
TI  - Radiographic remission in seropositive rheumatoid arthritis. A 20-year follow-up
      study.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is in most instances a progressive disease.
      Very little information is available on halting of the radiographic damage,
      particularly in later phases of the disease. We studied radiographic remission of
      RA lasting to the end of follow-up, covering the period 1973-96. METHODS:
      Radiographs of hands and feet were taken at onset and at 1, 3, 8, 15 and 20 years
      from entry in 102 cases of recent onset (< 6 months) seropositive and erosive RA.
      A Larsen score of 0-100 was formed for 20 joints of hands and feet. If the score
      did not worsen by more than one point between one of the above time points and
      the end of the study, the patient was considered to be in remission. RESULTS:
      Remission was confirmed in 27 (26%) of the patients. In 3 cases the remission was
      from the 1-year check-up, in 5 from the 3-year check-up, in 6 from the 8-year
      check-up and in 13 cases from the 15-year check-up. Some of the remission cases
      had a mild disease from the outset, but there were cases in which the disease
      process had led to marked joint destruction before slowing down. CONCLUSION: This
      data may serve as a basis for comparison with subsequent cohort studies on new
      treatments-of-choice.

PMID- 11579720
TI  - Midfacial swelling and oro-nasal involvement in a 53-year-old patient with
      bilateral pulmonary infiltrations.

PMID- 11579721
TI  - Emotional distress induced rhabdomyolysis in an individual with carnitine
      palmitoly-transferase deficiency.
AB  - A 48-year-old male patient with underlying CPT II enzyme deficiency is described.
      Emotional stress appeared to precipitate recurrent myalgias, rhabdomyolysis and
      reversible renal impairment over a 40-year period. Our search of the English
      literature indicates this to be the first time that the emotional stress has been
      documented to precipitate the CPT II syndrome. Although the pathogenesis of this
      syndrome has yet to be established, existing knowledge is briefly reviewed and
      the likely metabolic and neuroendocrine mechanisms which link emotional stress to
      muscle metabolism are examined. These mechanisms influence the extent of
      lipolysis or glycolysis that occurs during the process of muscle ATP generation.
      It is suggested that neuroendocrine and other stress related changes which favour
      lipolysis over glycolysis adversely affect muscle energy metabolism in patients
      whose mitochondria are deficient in CPT II enzyme. Possible treatment strategies
      are those that favour glycolysis over fatty acid metabolism and include a variety
      of ways of modulating sympathetic and parasympathetic tone. The use of
      carbohydrate supplementation beta-blockers and anxiolytic agents is discussed.

PMID- 11579722
TI  - A definite case of spondylodiscitis caused by Streptococcus equisimilis.
AB  - To shed light on the role of Streptococcus equisimilis (SE) in the pathogenesis
      of intervertebral disc infection, we report here a case of lumbar
      spondylodiscitis in a 37-year-old male caused by SE, with identification of this
      strain by cultures from L4-L5 lumbar disc biopsy. Intravenous therapy with
      penicillin and gentamycin combined with immobilization resulted in a rapid and
      complete recovery. The patient did not have underlying disease and showed no
      obvious history of exposure to animals. We conclude that SE may be responsible
      for both septic arthritis and spondylodiscitis.

PMID- 11579723
TI  - Influenza vaccination in children with chronic rheumatic diseases and long-term
      immunosuppressive therapy.
AB  - OBJECTIVE: To study the immunogenicity, safety and efficacy of influenza vaccine
      in children with chronic rheumatic diseases (CRD) receiving long-term
      immunosuppressive therapy. METHODS: Seventy children (F:M 51:19) with CRD (JIA =
      49, SLE = 11, other = 10) aged 4-17 yrs and 5 healthy siblings of the patients
      (aged < 11 yrs) received a "split type" influenza vaccine (Fluarix SB) licensed
      for the 1999-2000 winter season. Clinical and laboratory evaluation were
      performed at study entry and at 1, 3 and 6 months after vaccination. Blood
      samples were collected before and one month after vaccination and antibody titers
      to A/Beijing, A/Sydney and B/Beijing influenza antigens were measured using a
      standardized hemagglutination inhibition assay. RESULTS: Patients were assigned
      to groups according to the therapeutic regimen [prednisone (PDN), PDN plus 1
      disease modifying antirheumatic drug (DMARD), PDN plus 2 DMARDs and 1 or 2 DMARDs
      without PDN]. 5/70 patients reported local (3) or systemic (2) reactions and 1/5
      siblings local reaction. Nine more patients reported mild upper respiratory tract
      symptoms 1-4 weeks post-vaccination. No patient was found to fulfill criteria for
      deterioration or flare of the underlying disease. At completion of vaccination
      97.14% of patients developed protective HI titers to A/Beijing, 100% to A/Sydney
      and 80% to B/Beijing. No significant difference in the mean geometric titers was
      found between patients with different therapeutic regimens or age or between
      those with JIA or SLE. Disease activity was not related with response or non
      response to B/Beijing. No patient reported "flu-like" symptoms during the 6-month
      period of follow-up. CONCLUSION: The results of our study indicate that children
      with CRD receiving long-term immunosuppressive therapy at conventional doses
      respond to influenza vaccination similarly to healthy children without serious
      adverse reactions or disease flares regardless of their age, type of CRD or
      therapeutic regimen.

PMID- 11579724
TI  - Treatment with allopurinol decreases the number of acute gout attacks despite
      persistently elevated serum uric acid levels.

PMID- 11579725
TI  - Dermatomyositis and Graves' disease.

PMID- 11579727
TI  - [The surgical treatment of fractures of the base of the fifth metacarpal bone].
AB  - Fractures of the base of the fifth metacarpal bone are relatively uncommon
      injuries. In contrast to similar fractures of the first metacarpal bone, various
      methods of treatment have been advocated. Some believe that cast immobilization
      or immediate unrestricted motion is a reliable method, while others recommend
      surgery and pinning or plate fixation. Fractures of the base of the fifth
      metacarpal bone are inherently unstable and inadequate reduction may result in
      pain, functional disability and osteoarthritic changes. We retrospectively
      reviewed 14 cases with intra-articular or extra-articular fractures of the base
      of the fifth metacarpal bone between the years 1991-1998. Patient treatment
      included closed reduction and percutaneous pinning using an image intensifier.
      Open reduction with multiple Kirschner pinning was implied in comminuted
      fractures and in cases when closed restoration of the articular surface was
      unfeasible. On follow-up examinations, all patients had good functional outcomes
      with no arthritic changes. We recommend reduction, restoration of the articular
      surface and pinning as the method of choice in the treatment of these fractures.

PMID- 11579726
TI  - [Overuse of antibiotics with upper respiratory tract infections in a primary care
      clinic].
AB  - In the majority of cases upper respiratory tract infections (URI's) are caused by
      viruses. Nonetheless, in many instances, patients with URI's are over-treated
      with antibiotics. In order to evaluate the use of antibiotic therapy in patients
      with URI's, we recorded medications prescribed for URI's in 394 young adults
      seeking care in a primary care clinic. The following parameters were assessed:
      rhinnorhea, cough, sore throat, dysphagia, tonsillar exudates, tonsillar
      enlargement and cervical lymphadenopathy. Throat cultures were taken from all the
      patients. RESULTS: Antibiotic therapy was prescribed for 99 of the 370 patients
      (26.8%) with URI's and negative throat cultures. Among these patients, a high
      prevalence of the following findings was evident: tonsillar enlargement (66.7%),
      tonsillar exudates (48.5%), cervical lymphadenopathy (42.4%), lack of rhinorrhea
      (40.4%), lack of cough (32.0%) and fever (31.3%). CONCLUSIONS: Excess antibiotic
      therapy was prescribed for patients with URI's. Possible explanations are:
      clinical findings that suggest a diagnosis of follicular tonsillitis, early
      antibiotic treatment that is not based on throat cultures or antigen detection
      tests, and multiple treating physicians. RECOMMENDATIONS: We recommend that in
      cases of patients with URI's, antibiotics should not be prescribed unless
      diagnosis of a streptococcal infection is supported by results of throat cultures
      or antigen detection tests. Furthermore, in primary care clinics with a number of
      physicians, treatment should guarantee appropriate medical follow-up.

PMID- 11579728
TI  - [Diagnosis of idiopathic autonomic neuropathy].
AB  - This is a case report of a 51 years old woman admitted to the hospital due to
      abdominal pain and intractable diarrhea of two months duration. Her history and
      her physical examination revealed signs and symptoms leading to the diagnosis of
      the rare syndrome of idiopathic autonomic neuropathy. In this case report we
      briefly describe the characteristics of the syndrome and its natural history and
      treatment. We also raise the important issue of common error patterns in
      diagnostic reasoning such as "omission" and "anchoring" and how these patterns
      are reflected in the present case.

PMID- 11579730
TI  - [Malaria in Israel--a preventable disease].
AB  - This article deals with five cases of imported malaria among Haifa District
      citizens in 1999. Two patients died from multi-organ failure secondary to the
      infection. Malaria continues to be a serious health risk for travelers returning
      from endemic areas. Travelers require detailed advice on appropriate
      chemoprophylaxis against malaria and personal protection against mosquito bites.
      There has, however, been poor compliance to drug prophylaxis. Physicians should
      encourage travelers to seek advice from an accredited travelers clinic in advance
      of the trip. It is advisable for the physician to stress the importance of taking
      the recommended chemoprophylaxis.

PMID- 11579729
TI  - [Organophosphate poisoning in inexperienced workers].
AB  - Organophosphates are frequently used as insecticides in agricultural areas,
      therefore they may pose a risk for accidental exposure by dermal contact or
      through inhalation. We present the cases of eight young men, who worked
      unprotected and inexperienced with organophosphates. They were exposed dermally
      and developed mainly gastrointestinal symptoms and also diaphoresis,
      hypersalivation, blurred vision and miosis. One patient developed severe
      weakness, fasciculations, disorientation and sleepiness. All had low levels of
      plasma acetylcholinesterase. All were admitted to the hospital and received
      antidotal treatment of atropine and toxogonin. They were released after 48 hours
      in good physical condition. The hospital staff rapidly diagnosed the
      organophosphate intoxication; additional doctors and nurses were called to the
      emergency department. The patients were decontaminated in showers within the
      hospital. This case emphasizes the need for workers handling pesticides, to be
      supervised by an experienced person and the advantages of hospital drills in
      rapid diagnosis and preparedness to provide treatment to many patients.

PMID- 11579731
TI  - [Stromal tumors of gastrointestinal tract: clinical and pathological features].
AB  - During the period 1991 till 1999, ten patients with primary stromal tumors of the
      gastrointestinal tract (stomach, duodenum, jejunum, ileum and rectum) were
      treated. Nine patients underwent radical resection and one patient had non
      complete resection of the tumor. The median age of the group was 63 years for 7
      male and 3 female patients. The median follow-up period was 58 months. The tumor
      size was 4.5-17 cm. (median 10 cm.) The median survival was 43 months. Five
      patients remained alive without the disease (median survival 87 months). One
      patient died with no evidence of the disease after 12 months. One patient remains
      alive with liver metastases for 13 months and 4 patients died of metastatic
      disease (median survival 10 months). Features associated with decreased survival
      included tumor size > 5-8 cm., mitotic counts > 5 mitotic figures per 50 high
      power microscopic fields and high cellularity.

PMID- 11579732
TI  - [How do physicians actually write guardianship certificates for elderly
      patients?].
AB  - Physicians participate in the legal process of appointing guardianship by writing
      medical certificates concerning guardianship. There are no instructions or clear
      cut methods to examine how to determine a person's ability to handle his own
      affairs (estate and body), or to evaluate his ability to express his opinion
      concerning guardianship. There are, however, a number of ways to examine and
      analyze the subject. Our paper presents findings from 16 randomly collected
      medical certificates from diverse sources (13 different institutions, physicians
      from various specialties), for which the courts decision is known. We checked to
      see if the medical certificates relate to and fulfill basic medico-legal and
      clinical points referred to in the professional literature. RESULTS: We found
      that full demographic details were recorded in only one certificate (6.2%), the
      identity of the solicitor of the certificate was mentioned in 3 cases (18.7%) and
      the source/s of information in 6 cases (37.5%). Results of complete
      cognitive/mental examination (mental status) were mentioned in 4 cases (25%),
      psychiatric diagnoses in 12 cases (75%), level of severity in 9 cases (56.2%),
      reference to a temporary phenomenon in one case, and evaluation of basic daily
      functioning in 2 cases (12.5%). None of the cases included more complex daily
      functioning evaluations (instrumental). Similarly, none of the certificates
      mentioned whether or not legal criteria were used to evaluate the subjects
      ability to handle his estate or body or his ability to express his opinion
      concerning guardianship. On the other hand, formal reference to the ability to
      handle affairs (in 7 cases [43.7%] distinction between estate and body) and to
      express an opinion concerning guardianship was noted in 15 cases (93.75%). The
      length of the medical certificate averaged 13.8 lines (standard deviation 10.1,
      range 4-41); 13 of the certificates were written in public forums with an average
      length of 9.9 lines (standard deviation 4.6, range 4-20 lines), as opposed to 31
      lines (standard deviation 9.5, range 22-41) for the private sector. Our findings
      suggest that the medical certificates were lacking in clinical facets examined,
      especially the medico-legal aspects. Despite these shortcomings, the courts
      accepted the overwhelming majority of the documents (15/16, 93.7%), perhaps
      because most of the certificates included formal reference to specific legal
      questions raised in the court (ability to handle affairs, ability to express
      opinion concerning guardianship). In our opinion, these findings, if validated in
      larger groups and in more courts, require multi-system re-evaluation of the
      subject of writing medical certificates for legal guardianship of the elderly.

PMID- 11579733
TI  - [Vaginismus--a psychiatric perspective, "secrets" and other psychodynamic
      causes].
AB  - Vaginismus is a disorder involving both psychiatry and gynecology. Psychiatric
      help is sought in only a small proportion of cases, although it is probable that
      the psychological etiology of the disorder is more frequent than generally
      recognized. This article deals with the causes and psychological circumstances of
      the disorder. Five cases are presented. In the first three cases, primary
      vaginismus caused unconsummated marriage in young women of religious or
      traditional background. In these cases a "secret" was revealed relating to a
      previous sexually related experience. This provides the basis for therapy. The
      other cases describe secondary vaginismus which appeared in older women who
      developed the symptom after a number of years of marriage. This article discusses
      the different psychotherapeutic approaches for the two types of cases. In the
      former cases, therapy may be brief and the prognosis is favorable. In the second
      case type, there is often more significant personality or marital pathology
      requiring prolonged and extensive psychotherapy. The authors stress the need for
      physicians to be mindful of cases of vaginismus requiring psychiatric
      intervention rather than gynecological treatment.

PMID- 11579734
TI  - [The department of internal medicine--returned to its formal glory].

PMID- 11579735
TI  - [Association between mitral annulus calcification and atherosclerosis].
AB  - Mitral annulus calcification (MAC) is best diagnosed by transthoracic
      echocardiography. MAC is associated with known atherosclerotic risk factors such
      as diabetes mellitus, hypertension and hypercholesterolemia. It is also known
      from the literature that patients with MAC have higher prevalence of left atrial
      and left ventricular enlargement, hypertrophic cardiomyopathy, atrial
      fibrillation, aortic valve calcification and stenosis, various cardiac conduction
      defects, bacterial endocarditis, cardiovascular events and stroke, though the
      etiological basis is unknown. Pathological studies from the 80's present a theory
      that MAC is a form of atherosclerosis. During the past few years we conducted a
      few clinical studies in order to test this theory and to examine the association
      between MAC and known atherosclerotic phenomena. We found higher prevalence of
      aortic atheroma in patients with MAC, especially complex atheroma, and we also
      found a continuous correlation between the MAC and atheroma thickness. We also
      noted that MAC patients have a higher prevalence of carotid artery stenosis,
      coronary artery stenosis, peripheral artery stenosis and higher levels of anti
      beta 2-Glycoprotein I antibodies in patients with MAC thickness equal or greater
      than 5 mm. These studies support the theory that MAC is a form of atherosclerosis
      and define a group of patients with higher prevalence of atherosclerotic disease
      in multiple blood vessels.

PMID- 11579736
TI  - [Intraperitoneal chemotherapy in ovarian carcinoma].
AB  - Current standard treatment of ovarian carcinoma includes primary cytoreductive
      surgery followed by postoperative first-line intravenous combination chemotherapy
      with taxol and cisplatin. Despite a remarkable high initial response rate, the
      tumor recurs in most patients and its response to further surgery and additional
      lines of intravenous chemotherapy is dismal. Intraperitoneal chemotherapy is
      gaining impetus in relation to ovarian cancer since, even in an advanced stage or
      recurrence, it usually remains confined to the peritoneal cavity. Intraperitoneal
      chemotherapy allows direct exposure of the tumor to high concentrations of
      cytotoxic drugs without increasing systemic toxicity. A cytotoxic drug is
      considered qualified for intraperitoneal administration if its molecular weight
      is high enough not to permit an easy transfer through the peritoneal/plasma
      barrier. Intraperitoneal chemotherapy can be administered intraoperatively and/or
      post-operatively. The most common complication of intraperitoneal chemotherapy is
      peritonitis. A significant advantage of intraperitoneal first-line chemotherapy
      over intravenous first-line chemotherapy was demonstrated in only two of five
      phase III clinical trials. The results of eight phase II studies showed a
      borderline advantage of intraperitoneal consolidation chemotherapy over
      intravenous consolidation chemotherapy, or no consolidation chemotherapy. In 13
      phase II studies, a borderline advantage of intraperitoneal salvage chemotherapy
      over intravenous salvage chemotherapy was noticed only in patients with minimal
      residual disease. In five stage I/II studies, a vague advantage of
      intraperitoneal hyperthermic chemotherapy over other treatments was noticed.
      However, this treatment was well-tolerated by the patients. All studies
      demonstrated that patients with minimal residual disease are the best candidates
      for intraperitoneal chemotherapy. Additional phase III studies are required in
      order to reinforce the status of intraperitoneal chemotherapy in the treatment of
      ovarian carcinoma.

PMID- 11579737
TI  - [Respiratory impairments and aerobic physical activity in low-cervical spinal
      cord injuries].

PMID- 11579738
TI  - [Between metaphor and certainty: teaching an introductory course in complementary
      medicine].
AB  - In recent years it has been recognized that it is increasingly important to teach
      complementary medicine (CAM) in medical schools, residency programs and CME
      courses. We report our experience in teaching an elective introductory course in
      CAM to residents and specialists in the department of family medicine in the
      Bruce Rappaport Faculty of Medicine at the Technion, Haifa, Israel. Teaching four
      modules in CAM (herbal medicine, traditional Chinese medicine, homeopathy and
      nutritional medicine) during a 16-session course induced a positive change in the
      students attitude toward CAM and increased their interest in evidence-based CAM.
      In addition, the students increased their use of CAM for both themselves and
      their families, decreased their overall tendency to refer patients to CAM
      practitioners but increased their actual referral rate for patients who were
      considered to benefit from complementary treatment. The majority of the course
      participants considered teaching physicians CAM to be of great importance.

PMID- 11579739
TI  - [Overtraining in elite athletes--hormonal aspects].

PMID- 11579740
TI  - [Indulku: a popular magic-medical technique].

PMID- 11579741
TI  - [Ibuprofen--new era of an old drug].

PMID- 11579742
TI  - [Exposure to radon gas at schools, Cohen's paradox and public health policy].
AB  - Finding Radon levels above the legal threshold in schools and private homes has
      become an highly publicized problem in Israel, due to the rising awareness of the
      public to environmental matters and its influence on human health. However in the
      last decade a growing number of research reports have put serious doubts upon the
      validity of the scientific model used for assessing the health risk due to
      exposure to low intensity ionising radiation. The present paper surveys the
      development of the critics of the Linear No-Threshold Hypothesis (LNTH) that was
      used up to now as a scientific basis for public health policy in this field. The
      implications for the Israeli population and Health authorities are discussed. In
      the authors' opinion, controlling radon levels is an aim by itself,
      irrespectively of its causal relationship to lung cancer, and is part of a wider
      policy of maintaining the background exposure to ionizing radiation of the
      Israeli population to the lowest possible level. However its role in prevention
      of lung cancer morbidity and mortality is neglectable, and efforts must
      concentrate upon prevention and cessation of smoking. Smoking remains the most
      important preventable cause of lung cancer, and potentialize the effects of all
      other possible carcinogens.

PMID- 11579743
TI  - [Recommendations for earthquake preparedness in Israel].
AB  - Earthquakes have occurred in the past in our region, along the Afro-Syrian fault
      line and along the eastern border of Israel. Several earthquakes had a magnitude
      between 6.25 and 6.5 on the Richter scale and caused severe damage to the
      populated areas in the Galilee, the Judean Hills and along the coastline. The
      last major earthquake occurred in 1927 in the Jordan Valley and caused more than
      300 fatalities and extensive property damage. If we consider the present densely
      populated regions in the areas at risk, the occurrence of an earthquake with a
      magnitude of > 6.25 will constitute a major disaster, causing thousands of
      casualties and extensive property and economic damage. Israel is presently
      planning a comprehensive response to mitigate the damages by enforcing existing
      anti-seismic building codes, retrofitting of public buildings, including
      hospitals and utilizing all available manpower and material resources in case of
      such an event. The health sector is a vital part of the overall preparedness and
      response. Hospitals have to plan alternative sites for continued activity and
      increase the number of beds. Army medical teams will have to operate in the
      disaster area in conjunction and coordination with the Home Front Command rescue
      teams and the EMS. Public and primary health services will have to be reinforced
      to deal with acute and chronic health problems in the wake of the disaster. The
      burial of the dead and their identification will become a major logistic and
      emotional problem and must be planned in advance. Preparedness includes
      establishing contact with NGOs and agencies in countries, which may render
      medical assistance in such an event.

PMID- 11579744
TI  - [From Beilinson to Tel-Hashomer--historical marks to the development of the Sheba
      Medical Center 1948-1953].

PMID- 11579745
TI  - Exercise and oxidative stress: significance of antioxidants with reference to
      inflammatory, muscular, and systemic stress.
AB  - Many studies have demonstrated that intense muscular work generates considerable
      amounts of reactive oxygen species (ROS). In order to prevent oxidative stress,
      the body contains a large number of nonenzymatic and enzymatic antioxidants that
      either prevent ROS formation or scavenge radical species. Oxidative stress can
      lead to damage or destruction of cellular macromolecules such as lipids,
      proteins, and nucleic acids. Therefore, oxidative stress has been associated with
      decreased physical performance, muscular fatigue, muscle damage, and
      overtraining. It has been hypothesized that the body's physiological amount of
      antioxidants is not sufficient to prevent exercise-induced oxidative stress and
      that additional antioxidants are needed to reduce oxidative stress, muscular
      damage, or overshooting inflammation. However, some but not all investigations
      have demonstrated oxidative stress following physical exercise, and also,
      findings concerning the role of antioxidants in reducing oxidative stress are
      equivocal. In addition, a clear association between the amount of exercise
      induced muscular, metabolic, hormonal, or inflammatory stress and levels of
      antioxidant vitamins could not be established consistently. Therefore, although
      the theoretical background may be sound, there is no scientific evidence to
      recommend increased quantities of antioxidants to physically active people
      exceeding the amount provided by a healthy, balanced nutrition.

PMID- 11579746
TI  - Exercise and cytokines with particular focus on muscle-derived IL-6.
AB  - Exercise induces increased circulating levels of a number of cytokines. Thus,
      increased plasma levels of tumour necrosis factor (TNF)-alpha, interleukin (IL-1)
      beta, IL-1 receptor antagonist (IL-1ra), TNF-receptors (TNF-R), IL-10, IL-8, and
      macrophage inflammatory protein (MIP)-1 are found after strenuous exercise. The
      concentration of IL-6 increases up to 100 fold after a marathon race. Recently,
      it has been demonstrated that IL-6 is produced locally in contracting skeletal
      muscles and that the net release from the muscle can account for the exercise
      induced increase in arterial IL-6 concentration. IL-6 more than any other
      cytokine is produced in large amounts in response to exercise. It is produced
      locally in the skeletal muscle in response to exercise, and IL-6 is known to
      induce hepatic glucose-output and to induce lipolysis. This indicates that IL-6
      may represent an important link between contracting skeletal muscles and exercise
      related metabolic changes.

PMID- 11579747
TI  - Exercise-induced modulation of intracellular signaling pathways.
AB  - Intracellular signaling pathways transduce cellular activation, induced by ligand
      receptor ligation, into a cellular response like secretion or proliferation.
      Signaling processes involve either the release/formation of diffusible second
      messengers or the transfer of phosphate groups. These signaling cascades involve
      many steps sensitive to exogenous modulation and have been shown to be involved
      during the pathogenesis of several diseases. Therefore, the investigation of the
      regulation of cellular signal transduction mechanisms by exercise should be a
      valuable tool for a better understanding of exercise-induced immunomodulation.
      Within this review, important signaling pathways and their cross-talk in
      leukocytes are described. Furthermore, exercise related changes in metabolism,
      endocrine system, and environmental stress and their possible influence on
      intracellular signaling steps are discussed. Finally, recent published data about
      alterations in important signaling pathways by exercise are presented.

PMID- 11579748
TI  - The impact of psychological stress on immune function in the athletic population.
AB  - In many ways, the physiological and immune consequences of acute bursts of
      physical exercise parallel the effect of an acute psychological stressor.
      Similarly, the net effects of endurance training resemble chronic psychological
      stress, whereas the physiological milieu associated with overtraining resembles
      that of melancholic depression. We suggest that the prolonged psychological
      stress often associated with athletic training and competition may make athletes
      more vulnerable to the negative health effects of training. Furthermore, a
      relationship between anxiety and life events on susceptibility to injury is well
      documented. Individual differences in self-confidence and self-esteem are also
      known to relate to the occurrence of injury as well as recovery from injury. We
      suggest that these two observations may be linked. It is the purpose of this
      paper to review the most recent evidence that psychological stress does impact
      upon the balance of the immune system in such a way as to be relevant to health
      outcomes and that the athletic population, in particular those with low self
      esteem, may be especially vulnerable due to the probable synergistic effects of
      both physical and psychological stress.

PMID- 11579749
TI  - Free radicals, exercise, apoptosis, and heat shock proteins.
AB  - Free radicals are an integral part of metabolism and are formed continuously in
      the body. Many sources of stress heat, irradiation, hyperoxia, inflammation and
      any increases in metabolism including exercise, injury, and even repair processes
      lead to increased production of free radicals and associated reactive oxygen or
      nitrogen species (ROS/RNS). Evidence is accumulating that free radicals have
      important functions in the signal network of cells, including induction of growth
      and apoptosis and as killing tools of immunocompetent cells. Endogenous and
      nutritional antioxidant systems have to be adjusted to ensure adequate removal of
      radicals during stress to prevent damage to membranes, proteins, or nucleic
      acids. Excessive stress will induce DNA damage in the form of oxidized
      nucleosides, strand breaks, or DNA-protein crosslinks. Possible consequences of
      DNA damage are repair, apoptosis/necrosis, or defective repair leading to DNA
      sequence alterations and possibly to the development of cancer or, in case of
      mitochondrial DNA, to metabolic dysfunction. Excessive exercise will also induce
      DNA damage in peripheral leukocytes. The good message is that moderate stress in
      form of regular exercise/training may have protective effects against exercise
      induced DNA damage. Up-regulation of endogenous antioxidant defense systems and
      complex regulation of repair systems such as heat shock proteins (HSP 70, HSP 27,
      HO 1) are seen in response to training and exercise. Up-regulation of
      antioxidants and modulation of the repair response may be mechanisms by which
      exercise can beneficially influence our health. Massive intervention into the
      redox state by pharmaceutical doses of exogenous antioxidants should be regarded
      with caution due to the ambiguous role of free radicals in regulation of growth,
      apoptosis, and cytotoxicity by immunocompetent cells.

PMID- 11579750
TI  - Adaptation to exercise-induced oxidative stress: from muscle to brain.
AB  - Exercise increases the generation of reactive oxygen and nitrogen species (RONS)
      and by causing adaptation, could decrease the incidence of RONS-associated
      diseases. A single bout of exercise, depending upon intensity and duration, can
      cause an increase in antioxidant enzyme activity, decrease levels of thiols and
      antioxidant vitamins, and result in oxidative damage as a sign of incomplete
      adaptation. Increased levels of RONS and oxidative damage are initiators of a
      specific adaptive response, such as the stimulation of the activation of
      antioxidant enzymes, thiols, and enhanced oxidative damage repair. Regular
      exercise has the capability to develop compensation to oxidative stress,
      resulting in overcompensation against the increased level of RONS production and
      oxidative damage. Regular exercise causes adaptation of the antioxidant and
      repair systems, which could result in a decreased base level of oxidative damage
      and increased resistance to oxidative stress.

PMID- 11579751
TI  - Can CAM cut costs?

PMID- 11579752
TI  - Rurals need active pharmacists.

PMID- 11579753
TI  - CPOE systems not ready yet.

PMID- 11579754
TI  - Overcrowding. Chaos in your ED? Look on the bright side.

PMID- 11579755
TI  - Information technology. Not taken with tech.

PMID- 11579756
TI  - Risk management. A Stark exception.

PMID- 11579757
TI  - Workforce shortage. Skipping gimmicks, keeping nurses.

PMID- 11579758
TI  - Staffing ratios. Kaiser steps up.

PMID- 11579759
TI  - Patient satisfaction. More feedback.

PMID- 11579760
TI  - Nursing. Private eyes.

PMID- 11579761
TI  - Allocating scarce resources.

PMID- 11579762
TI  - Turnarounds. Parkland restitches the safety net.

PMID- 11579763
TI  - 1Q[3a]. Does health care need to refocus on AIDS?

PMID- 11579764
TI  - One of our own.

PMID- 11579765
TI  - 2001 salary survey.
AB  - Boards are coming to respect how challenging it is to run a hospital, and
      increasingly view it as too big a job for one person. In our annual compensation
      survey report, Hay Group analysts assert that lower-level executives, senior
      managers and even middle managers have seen their stock rise in health care
      organizations, and that's reflected in the pay structure. Even so, CEOs aren't
      exactly struggling--but their total compensation still lags behind that of their
      counterparts in other industries.

PMID- 11579766
TI  - A leadership vacuum.
AB  - More and more frequently, hospital CEOs face a daunting question about the future
      of their organizations: Who will replace me when I retire? A severe talent drain
      has hit health care management. Executive searches take longer, fewer candidates
      vie for jobs, and there is a trend among hospital CEOs to retire earlier. The
      traditional development process, such as residencies and fellowships--and most
      importantly, mentoring by CEOs--has waned. Savvy organizations are attacking the
      problem in a number of innovative ways.

PMID- 11579767
TI  - Beyond managed care.
AB  - Even as the federal government tries to prop up Medicare managed care, HMOs
      continue to pull out of the program. But a Centers for Medicare & Medicaid
      Services demonstration project aims to show that one concept of managed care can
      keep chronically ill patients healthier and lower overall costs. The concept,
      coordinated care, blends case management and disease management, giving patients
      the resources to manage their own care more actively. But, please, just don't
      call it managed care.

PMID- 11579768
TI  - A cultural gap.

PMID- 11579770
TI  - Thyroid disease: an overview.
AB  - This article reviews thyroid anatomy and physiology, then presents a variety of
      common thyroid disorders, including hyper- and hypothyroidism, goiters,
      cretinism, thyroiditis and several types of thyroid cancer. Prevention of thyroid
      disease is discussed, along with medical imaging techniques for evaluating the
      thyroid gland.

PMID- 11579769
TI  - Student perceptions of clinical mistreatment.
AB  - This study examined radiography students' perceptions regarding mistreatment
      during the clinical portion of their education. Results suggest that a majority
      of students perceived mistreatment and that second-year students were 4 times
      more likely to perceive mistreatment than first-year students. Most students who
      perceived mistreatment indicated that the abuse was verbal and came primarily
      from staff technologists. Most perceived the mistreatment to be slightly
      important and slightly upsetting. However, approximately one third perceived the
      mistreatment to be very important and very upsetting. As part of the study,
      students were asked to suggest preventive measures that could help eradicate
      abusive behavior in the clinical setting.

PMID- 11579771
TI  - Breast cancer: diagnosis, treatment and prognosis.
AB  - This article reviews staging of breast cancer and treatment protocols for the
      disease, then examines several different types of breast cancer. Each type is
      described in terms of its mammographic, sonographic and histologic appearance,
      along with its treatment and prognosis. The author concludes with a discussion of
      magnetic resonance imaging's role in breast cancer detection and treatment
      planning.

PMID- 11579772
TI  - Uterine fibroid embolization.

PMID- 11579773
TI  - Didactic and clinical competency.
AB  - Because the ARRT's mission is to recognize individuals "qualified" in the use of
      ionizing and nonionizing radiation for medical imaging and radiation therapy, it
      falls upon the ARRT to define what "qualified" means. The goal of the competency
      project was to further refine our definition of what qualified means as it
      relates to educational preparation and to incorporate that refined definition
      into existing eligibility requirements. Certification requirements should be both
      specific and public. The competency requirements accomplish this for ARRT's
      educational eligibility requirements and will help advance certification as well
      as education in the profession.

PMID- 11579774
TI  - Programmatic accreditation's value.
AB  - When the elements of educational quality, radiation safety and protection of
      student rights are considered, the value of JRCERT accreditation is apparent.
      Programs can be confident that the JRCERT Standards support their educational
      goals and objectives. Students can be confident that the education they receive
      will prepare them to function as entry-level professionals as determined by
      national standards. Radiation therapists and radiographers can be confident their
      coworkers were appropriately educated and are able to fulfill the
      responsibilities of these professional positions. Employers across the country
      can be confident that graduates possess fundamental skills regardless of the
      JRCERT-accredited program the graduate attended. Lastly, patients can be
      confident that their radiographic procedures are performed competently.

PMID- 11579775
TI  - 2001 Ed C. Jerman Memorial Lecture. I'm not just a "tech".

PMID- 11579776
TI  - CE's effectiveness depends on you.

PMID- 11579777
TI  - Making a difference in Russia.

PMID- 11579778
TI  - Foreign affairs.

PMID- 11579779
TI  - Help young people tackle the problem of psoriasis.

PMID- 11579780
TI  - Reflex sympathetic dystrophy syndrome following herpes zoster.
AB  - Reflex sympathetic dystrophy syndrome (RSDS), or algodystrophy, is a poorly
      understood, painful syndrome that consists of multiple symptoms, including
      vasomotor instability, swelling, and chronic pain involving an extremity.
      Although RSDS following herpes zoster is classically recognized, only a few well
      documented cases of this complication have been reported to date. We present the
      case of a 63-year-old white woman with characteristic signs and symptoms of RSDS
      in the left upper limb that appeared 3 weeks after she had a typical herpes zona
      involving the left C5-C6 dermatomes. Early diagnosis and treatment with
      physiotherapy, intranasal salmon calcitonin, and oral calcium achieved a
      progressive improvement of the disease, which healed without sequelae in a brief
      time.

PMID- 11579781
TI  - Two familial cases of perianal streptococcal dermatitis.
AB  - Two cases of perianal streptococcal dermatitis (PSD) occurred in a brother and
      sister, aged 4 and 6 years, respectively. The diagnosis was confirmed by the
      detection of group A beta-hemolytic streptococci in the perineal area and pharynx
      of both patients. We emphasize the importance of a quick and accurate diagnosis
      of the infection because PSD is frequently confused with other perianal diseases
      of infancy.

PMID- 11579782
TI  - What is your diagnosis? Allergic contact dermatitis to paraphenylenediamin in a
      temporary henna tattoo.

PMID- 11579783
TI  - Botanical briefs: prickly pear cactus--Opuntia Miller.

PMID- 11579784
TI  - Dermatologic surgery into the next millennium, Part III.
AB  - Face-lift procedures and blepharoplasties are performed as in-office surgeries.
      Either local sedation or conscious sedation is used, and the patient's vital
      signs are carefully monitored. To avoid complications, the patient is followed
      closely postoperatively. It is highly suggested that the patient receives a
      medical clearance prior to undergoing either of these procedures.

PMID- 11579785
TI  - Sarcoidosis with giant parotomegaly.
AB  - We report the case of a 63-year-old man with bilateral parotid gland sarcoidosis.
      Giant, elastic, hard, subcutaneous tumors had been present on the right parotic
      and submaxillary regions for 11 years and on the left for 1 year. The patient had
      had diabetes mellitus for 8 years. Noncaseating epithelioid cell granulomata were
      revealed histopathologically in the periductal area of the parotid gland.
      Bilateral hilar lymphadenopathy was noted on chest x-ray studies. Serum levels of
      lysozyme were increased. Levels of serum angiotensin-converting enzyme were
      within normal limits. Tuberculin skin reaction was positive. The tumors gradually
      improved after treatment with oral minocycline. Giant parotomegaly, as it
      occurred in this case, is very rare.

PMID- 11579786
TI  - Selecting topical and systemic agents for recurrent aphthous stomatitis.
AB  - Recurrent aphthous stomatitis (RAS) is one of the most common oral diseases
      worldwide. Although the exact etiology of RAS remains unknown, a variety of
      topical and systemic preparations may be used for palliation or prevention. In
      most patients with RAS, topical agents, including over-the-counter preparations
      such as amlexanox, prescribed corticosteroids, or antimicrobial agents, are
      sufficient to control the disease. Patients with frequent exacerbations or those
      with a severe form of RAS that is unresponsive to topical treatments often
      require systemic agents to control their disease. These include corticosteroids,
      colchicine, dapsone, pentoxifylline, and thalidomide. All therapies are
      palliative, and none result in permanent remission.

PMID- 11579787
TI  - Diagnostic criteria for Gianotti-Crosti syndrome: a prospective case-control
      study for validity assessment.
AB  - No criteria exist for the modern diagnosis of Gianotti-Crosti syndrome (GCS). Our
      study objectives were to determine diagnostic criteria for GCS and to assess
      their validity using a prospective case-control design. We reviewed the clinical
      features of children with GCS who were reported in the literature from 1996 to
      2000 and proposed a set of diagnostic criteria. We documented clinical features
      of children younger than 18 years who were diagnosed over a period of 18 months
      as having GCS and of control subjects given (over the same period) differential
      diagnoses of GCS. Forty-two children were recruited (11 with GCS and 31 controls
      with differential diagnoses of GCS). All children with GCS, and none of the
      controls, fulfilled the set of diagnostic criteria as a whole. We conclude that
      the proposed criteria are practical valid criteria for diagnosing GCS.

PMID- 11579788
TI  - Long-term colchicine for recalcitrant palmoplantar pustulosis: treatment outcome
      in 3 patients.
AB  - Palmoplantar pustulosis (PPP) is a chronic, relapsing, pustular eruption
      affecting the palms and soles for which treatment is often difficult and
      frustrating. Short-term colchicine has been used to treat PPP with variable
      response. We report on the successful treatment of 3 patients with severe,
      therapy-resistant, chronic PPP. We observed significant reduction in the
      frequency of pustular eruptions and the number of pustules with maximum tolerable
      doses of colchicine treatment for up to 12 months.

PMID- 11579789
TI  - Plantar fibromatosis: use of magnetic resonance imaging in diagnosis.
AB  - For patients presenting with classic features of plantar fibromatosis, a
      presumptive diagnosis may be made on clinical grounds alone. In less clear cases,
      a biopsy may allow confirmation of the diagnosis; however, a biopsy exposes the
      patient to operative complications. Magnetic resonance imaging (MRI) offers a
      noninvasive method for confirmation of the clinical diagnosis that may obviate
      the need for a biopsy. We describe a case that demonstrates the potential of this
      technique.

PMID- 11579790
TI  - Primary skeletal muscle lymphoma presenting as refractory cellulitis.
AB  - The right torso of a 55-year-old woman showed diffuse skin and soft-tissue
      changes suggestive of cellulitis. However, several clinical and radiologic
      features, including the subacute and non-toxic nature of the illness and the
      patient's lack of response to antibiotic therapy, indicated a noninfectious
      etiology. Malignancy was suggested by striking changes seen on computed
      tomographic scanning--including extensive infiltration and enlargement of the
      musculature of the right shoulder girdle, the intercostal musculature, the
      latissimus dorsi, and the rhomboids; focal enlargement of the right paraspinal
      muscles; and enlargement of the psoas and the iliacus muscles and of the
      musculature around the hip joint. The mediastinal, hilar, and paraaortic regions
      showed no adenopathy. A large hypodense lesion of approximately 4.5 cm, which was
      seen in the caudate lobe of the liver, raised the concern of a metastatic focus
      of malignancy. Because of these findings, an immediate muscle biopsy was
      performed. Results showed a non-Hodgkin's lymphoma with a B-cell phenotype.
      Although primary skeletal muscle lymphoma is very uncommon in patients without
      human immunodeficiency virus infection, clinical presentation of refractory
      cellulitis, as seen in the current case, is extremely rare.

PMID- 11579791
TI  - Onychogryphosis in elderly persons: an indicator of long-standing poor nursing
      care? Report of one case and review of the literature.
AB  - A 92-year-old immobilized white woman under the daily nursing care of a private
      ambulatory nursing service displayed acquired deformities of the toenails
      resembling a ram's horn. In light of a rapidly growing elderly population, this
      case report illustrates the need for close monitoring of the quality of care that
      nursing services provide to older persons. In addition, it reviews the clinical
      aspects of onychogryphosis, as well as its pathomechanisms and treatment options.

PMID- 11579792
TI  - Volunteer experience in Tanzania, Africa.

PMID- 11579793
TI  - Advances in pain management good for patients and physicians.

PMID- 11579794
TI  - Long-term opioid analgesia and chronic non-cancer pain.

PMID- 11579795
TI  - State Medical Society of Wisconsin statement on the use of opioids for the
      treatment of chronic pain.

PMID- 11579796
TI  - New ways to define conditions related to pain and addiction.

PMID- 11579797
TI  - Definitions related to the use of opioids for the treatment of pain.

PMID- 11579798
TI  - Cases involving discipline for inappropriate prescribing of controlled
      substances.

PMID- 11579799
TI  - Chronic pain rehabilitation: principles and practice.
AB  - Chronic pain affects more than 50 million Americans and costs the economy
      billions of dollars each year. Because chronic pain may involve physical,
      emotional and social-role dysfunction, treatments that only address the physical
      problems are often ineffective. In chronic pain rehabilitation, a team of skilled
      professionals employs multiple therapies and a structured treatment plan to
      address all the dimensions of chronic pain. Patients undergoing pain
      rehabilitation demonstrate lasting reductions in pain, improved coping skills,
      and improved physical and social function. This article reviews the basic
      principles and current practice of chronic pain rehabilitation, with a guide to
      the evaluation techniques and therapies employed to aid these most challenging
      patients.

PMID- 11579800
TI  - Attitudes and approaches to acute ischemic stroke in Wisconsin hospitals.
AB  - Although acute stroke is a common presentation to an emergency room, the
      presentation of a patient with acute ischemic stroke, within a limited time
      window as an appropriate candidate for cerebral thrombolysis, is not common. In
      many of these patients, their candidacy can be improved through community
      education toward emergent transfer to an emergency room if they manifest symptoms
      of stroke. This would improve the "symptom-to-door" time. Another goal is to
      improve the recognition and approach of the hospital itself toward improving the
      "door-to-drug" time in appropriate patients. The obstacle to this second goal
      does not seem to be a nihilistic or evasive attitude on the basis of this study.
      Contrary to what was expected, enthusiasm for the use of cerebral thrombolysis
      was found in emergency physicians of all hospital categories, particularly of
      small remote hospitals. Instead, educational initiatives should focus on the
      facilitation of protocols for present and future ischemic stroke therapy,
      particularly in larger remote facilities that may be more self-dependent in their
      approach to acute stroke. An equally important focus should be toward more active
      participation by local neurologists who may be available for acute stroke care.
      Further, as this study demonstrates a correlation between the involvement of a
      local neurologist and the use of a stroke protocol, neurologists of non-tertiary
      facilities should be recruited to participate in these educational initiatives.

PMID- 11579801
TI  - Assessing the quality of life in children with cystic fibrosis.
AB  - Although patients with cystic fibrosis (CF) are experiencing increased longevity,
      it is unclear that improved quality of life (QoL) accompanies the greater
      quantity of life. This is especially true of children with CF where the burdens
      of treatment are substantial. Assessing QoL in such children is difficult, and
      only one instrument--the Quality of Well-Being (QWB) scale--seems to have been
      used extensively to assess QoL in children with CF. After thoroughly reviewing
      the literature, we surveyed the 113 certified CF centers in the United States
      about QoL assessment. With 84% responding, it was found that only 7 centers are
      assessing QoL--4 have been using the QWB instrument. Concurrently, we pilot
      tested the QWB instrument in children being followed longitudinally in the
      Wisconsin CF Neonatal Screening Project. Our results indicated that QWB scores
      reflecting QoL decreased as the number of respiratory infections increased, as
      the number of concurrent medical conditions increased, and as the number of
      different medications increased. However, we recognized problems with the
      assessed domains and data interpretation. In fact, the QWB instrument has limited
      sensitivity and responds more to the extent of physician-determined treatment
      than to QoL. There is a need for more QoL assessment and better instruments,
      particularly in young children with CF.

PMID- 11579803
TI  - 'Modern medicine' includes pain management and sensitive end-of-life care.

PMID- 11579802
TI  - Urban Wisconsin pediatric patients using an after-hours telephone triage service:
      outcomes and compliance.
AB  - OBJECTIVE: Evaluate the ability of a telephone triage service (TTS) to assess
      illness acuity of and patient compliance with advice given. DESIGN:
      Retrospective, observational study. PATIENTS: Patients of an urban, academic,
      pediatric clinic whose parents or caregivers called the TTS between July 23, 1997
      and August 23, 1997. OUTCOME MEASURES: Patient outcomes and visit information at
      related medical encounters subsequent to a TTS call. RESULTS: Patients were
      primarily African-American, under age 5, enrolled in a Medicaid HMO, and most
      often called for fever, HMO authorization, or asthma. Homecare and PED referrals
      were the two most frequent dispositions; overall compliance rate was 60%. No
      patient referred for non-emergent care required care on an urgent or emergent
      basis. CONCLUSIONS: Initial results suggest that the TTS can effectively evaluate
      illness acuity in an urban population and compliance with advice is reasonable. A
      TTS may offer significant benefits to ensure care quality and contain costs in
      this population.

PMID- 11579804
TI  - Increasing lipid testing in African-Americans with diabetes.

PMID- 11579805
TI  - Gallbladder cancer: recent advances and current guidelines for surgical therapy.

PMID- 11579806
TI  - The current status of minimally invasive off-pump coronary bypass.

PMID- 11579807
TI  - Endovascular therapy for ruptured abdominal aortic aneurysms.

PMID- 11579808
TI  - The complications and downside of endovascular therapies.

PMID- 11579809
TI  - The natural history of abdominal aortic aneurysms and their risk of rupture.

PMID- 11579810
TI  - Adult-to-adult living liver transplantation.

PMID- 11579811
TI  - Standardization of the extent of lymphadenectomy for gastric cancer: impact on
      survival.

PMID- 11579812
TI  - Laparoscopic repair of giant paraesophageal hernia.

PMID- 11579813
TI  - Radiofrequency ablation of primary and metastatic malignant liver tumors.
AB  - The use of RF energy to treat unresectable liver tumors is unlikely to be
      curative for most patients; however, a subset of patients treated with RFA may
      achieve long-term disease-free survival. Longer follow-up of hepatic tumor
      patients treated with RFA is needed to determine long-term disease-free and
      overall survival rates. New metastatic tumors develop in many of these patients
      at an incidence rate comparable with those treated with surgical resection or
      cryoablation. Surgical resection remains the gold standard for treating
      metastatic and primary liver tumors; however, few patients are candidates for
      hepatic resection because of tumor size, number, location, or the presence of
      cirrhosis too severe to permit liver resection. Cryoablation of unresectable
      tumors has been an option for several years, but complications associated with
      the freezing of tissue can be problematic. RFA of unresectable liver tumors
      provides a relatively safe, highly effective method to achieve local disease
      control in some liver cancer patients who are not candidates for liver resection.
      Ongoing research and refinements in RF techniques and equipment may permit
      effective treatment of larger liver tumors and of malignant tumors at other body
      sites. Combining RFA of liver tumors with regional and/or systemic adjuvant
      treatments is being studied in attempts to reduce the incidence of development of
      new metastases and, thus, improve the overall survival rates of these patients.

PMID- 11579814
TI  - Abdominal compartment syndrome: recognition and management.

PMID- 11579815
TI  - New adjuvant therapies for esophageal cancer.

PMID- 11579816
TI  - Hypertonic saline for resuscitation of the patient in shock.

PMID- 11579817
TI  - The current management of hepatic trauma.
AB  - Nonoperative treatment is best for hemodynamically stable patients with blunt
      liver injuries and in selected patients with penetrating injuries. However, most
      patients with penetrating injuries require early surgical intervention to control
      life-threatening hemorrhage or manage associated injuries. It is important to
      determine early in the course of operation if an abbreviated laparotomy and
      packing are indicated. In patients with persistent hemorrhage that cannot be
      controlled by surgical means, immediate transfer to the angiography suite for
      selective embolization may be a lifesaving alternative. Surgeons should not
      hesitate to operate on a patient for complications, but many of these can be
      managed by delayed, less-invasive procedures such as angiography, CT-guided
      drainage of collections, laparoscopy, or endoscopic retrograde
      cholangiopancreatography.

PMID- 11579818
TI  - The relationship between trauma center volume and outcome.
AB  - In spite of the limited direct evidence available, increasing data support a
      positive volume-outcome association in trauma care. When coupled with the
      extensive indirect data suggesting that regions with organized systems of trauma
      care are associated with lower trauma-related mortality rates than regions where
      the number of centers and their level of commitment are unlimited and untested,
      there is little doubt that experience improves outcome and that volume plays a
      critical role in the accrual of experience. Although regionalization of trauma
      care has the inevitable consequence of increased prehospital transport times,
      particularly in rural areas remote from large trauma centers, some states have
      designed inclusive systems where a large number of smaller centers have been
      verified and designated as lower level trauma centers (i.e., level 3-5). The
      process of trauma center verification holds these smaller volume centers to a
      standard of care such that the quality of care of the trauma patient may exceed
      that of other, less-regulated aspects of medical or surgical care. Several
      reports have suggested that trauma outcomes in smaller rural level 3 centers or
      centers with dedicated trauma programs with appropriate, functional triage
      protocols are comparable to national norms, thus reflecting the importance of
      commitment to outcome. These data suggest that quality of care does not only
      follow volume, particularly when stipulations and requirements are clear
      regarding the process of care and ongoing quality assurance.

PMID- 11579819
TI  - Management of the complex abdominal wall wound.

PMID- 11579820
TI  - [QT dispersion in DDD and VVI paced patients after myocardial infarction or with
      left ventricular hypertrophy].
AB  - The aim of this study was to assess the alterations of stroke volume (SV) on the
      QT dispersion (QTD) as a result of different pacing modes and programmed AV
      delays in patients (pts) after myocardial infarction (MI) or with left
      ventricular hypertrophy (LVH). We studied 14 MI pts (9 M, 5 F) in mean age 72.3
      +/- 3.7 yrs (Group I) and 12 pts with LVH (7 M, 5 F) in mean age 67.3 +/- 5.9 yrs
      (Group II), in whom DDD pacemakers were implanted due to complete
      atrioventricular block. The control group (Group III) consisted of 9 pts without
      MI or LVH. In all cases basic rate of the pacemaker was programmed at 70/min.
      Resting ECG showed all atrial and ventricular complexes captured. AV delay
      optimization was based on the measurements of SV by Doppler echocardiography. QT
      intervals (QTi) were measured from 12-lead ECG at 50 mm/s speed. QTD was
      calculated as the difference between maximal and minimal QTi. It was measured at
      optimal (opt. DDD, with highest SV) and "unoptimal" (unopt. DDD) programmed AV
      intervals and then in VVI mode (with lowest SV) after following reprogramming of
      the pacemaker. In Group I and II, a strong correlation between SV and QTD was
      found (R = 0.816 and -0.897, respectively). In control group, it was
      insignificant (R = -0.339). In VVI mode SV was significantly lower than in unopt.
      DDD (in Mi pts: 56.1 ml vs 71.1 ml, respectively, p < 0.01; in LVH pts: 64.1 ml
      vs 96.7 ml, respectively, p < 0.005) and QTD was significantly greater (74.8 ms
      vs 66.8 ms, respectively, p < 0.005 and 70.0 ms vs 53.5 ms, respectively, p <
      0.005). In LVH pts or MI pts programming of different AV intervals and pacing
      modes significantly influences QTD.

PMID- 11579821
TI  - [Troponin and its diagnostic values in ischemic heart disease].
AB  - The determination of biochemical markers of myocardial injury plays beside the
      electrocardiographic changes and the clinical signs the significant role in acute
      coronary syndromes. The most specific and sensitive markers are cardiac isoforms
      of troponin I and T. The advantages of troponins level determination should be
      considered in the cases of inconclusive results of the conventional markers, for
      example during surgical procedures. This applies especially to the cardiac
      surgery. The serum troponin concentration is elevated in many cases of unstable
      angina pectoris and is an important predictor of acute cardiovascular events and
      sudden death. This method allows also assessment of therapeutic success of
      reperfusion therapy and predicts potency of infarct related artery. The use of
      platelets receptors IIb/IIIa inhibitors or low molecular weight heparin in the
      case of troponins elevation was identified to improve the patients prognosis. The
      clinical value of troponins level determination in acute coronary syndromes was
      discussed in this paper.

PMID- 11579822
TI  - [Possibilities of subjective and objective evaluation of spasticity].
AB  - In this paper the most commonly used methods of assessment patients with
      spasticity has been presented. "Measuring" of spasticity is necessary for
      evaluation of new methods of treatment. This could be made directly or indirectly
      -in that case the sequela of spasticity is measured. In this elaboration as well
      subjective as objective methods of examination in spasticity has been described.
      The tone intensity scales, spasm frequency scores, global scales of motor
      impairment, ADL scales, upper extremity dexterity and strength testing,
      examination techniques and maneuvers to differentiate rectus femoris from
      iliopsoas and gastrocnemius from soleus tightness, clinical gait scores, EMG and
      goniometric pendulum test has been mentioned.

PMID- 11579823
TI  - [Non-pharmacological treatment of hypertension in practice of primary care
      physicians].
AB  - The role of non-pharmacological methods in prevention and treatment of
      hypertension is well documented. Weight in patients with overweight and obesity,
      sodium intake restriction and alcohol drinking limitation are especially
      effective in arterial pressure reduction. The aim of this questionnaire study was
      to evaluate the knowledge and skills in that field of physicians working in
      primary health care. The study was done with 91 physicians working in Warsaw
      District. All of them declared that they give instructions about life style to
      their patients with hypertension. In majority it was oral consultation (36
      persons, 39%) or oral consultation with distribution of booklets or brochures (48
      persons, 52%). Six physicians (7%) sent patients to specialist. Pharmacological
      treatment was started most often from the systolic pressure 160 mmHg (59 persons,
      64%) and diastolic pressure 100 mmHg (39 persons, 42%). Non-pharmacological
      advice was given most often at systolic pressure above 140 mmHg (44 persons, 48%)
      and diastolic pressure above 90 mmHg (67 persons, 73%). Salt intake reduction was
      advised always or usually by 82 physicians (90%), alcohol drinking reduction by
      77 persons (85%) and tobacco smoking cessation by 86 persons (95%). Regular
      physical activity was advised always or usually by 75 persons (82%). Evaluation
      of nutrition was done predominantly by asking a few not-formal questions (62
      persons, 67%). Only 1 physical used daily diary of nutrition. Similarly in
      evaluation of physical activity 62 persons (67%) used only not-formal questions.
      It is worthily to note that 36 persons (40%) considered that they need more
      skills to give advices of healthy life style, 49 persons (53%) did not enough
      time to do that and 30 persons (33%) thought that it is hard to give advices they
      can't keep themselves. All questionnaire physicians declared to use non
      pharmacological treatment in patients with hypertension. Quite good knowledge of
      essential recommendations in that field was stated. The results of this
      questionnaire indicate that many physicians estimate their knowledge and skills
      as low in that sphere.

PMID- 11579825
TI  - [Tumor necrosis factor alpha and interleukin 1-beta in serum of patients with
      tick-borne encephalitis].
AB  - The purpose of this work was to evaluate the changes of IL-1 beta and TNF-alpha
      serum concentrations among patients with TBE (tick-borne encephalitis) of mild
      and severe clinical course. The detection of cytokines was performed by
      immunometric assay twice before and after treatment. There was no significant
      changes in IL-1 beta serum concentration after treatment in both groups of
      patients. But concentration of TNF-alpha decreased significantly after treatment
      in both groups of patients. It seems that changes of TNF-alpha concentration
      might be helpful in evaluation of efficacy of aseptic central nervous system
      treatment.

PMID- 11579824
TI  - [Tumor necrosis factor alpha and its soluble receptors in serum of patients with
      coronary artery disease].
AB  - TNF-alpha as a pleiotropic, proinflammatory cytokine seems to play a role in the
      pathogenesis of atherosclerosis and coronary artery disease (CAD). TNF-alpha is
      binding to two cell surface receptors and its serum activity is modified by
      soluble forms of these receptors: sTNF-R I and sTNF-R II. The aim of this study
      was to assess serum concentrations of TNF-alpha, sTNF-R I and sTNF-R II in
      patients (pts) with CAD. We examined serum concentrations of TNF-alpha, sTNF-R I
      and sTNF-R II by ELISA in: 45 pts with stable exertional angina (group I); 32 pts
      with unstable angina (group II) within 6, 24, and 48 h after the chest pain; and
      23 pts before and 6, 24, and 48 h after PTCA (group III). The control group
      (group C) consisted of 20 healthy subjects. We evaluated: clinical state of
      patients and results of some diagnostic examinations (lipids, ECG,
      echocardiography, coronary angiography). Mean serum concentrations of TNF-alpha
      were significantly higher in pts ith CAD (group I: 18.25 +/- 5.5 pg/ml; group II:
      17.24 +/- 4.0 pg/ml; group III: 18.70 +/- 0.6 pg/ml; p < 0.001) than in healthy
      pts (8.31 +/- 1.4 pg/ml). In turn mean serum concentrations of sTNF-R I were
      significantly higher both in group I (1399.6 +/- 536.3 pg/ml; p < 0.05) and III
      (1544.0 +/- 391.4 pg/ml; p < 0.01) than in control group (1093.9 +/- 456.9
      pg/ml). There were not differences in mean serum concentrations of sTNF-R II. We
      found no differences between mean serum concentrations of TNF-alpha, sTNF-R I and
      sTNF-R II either after the chest pain (group II); or before and after PTCA (group
      III). In group I mean TNF-alpha correlated with serum triglycerides and HDL
      cholesterol (r = 0.412 and r = -0.424; p < 0.01); sTNF-R I correlated with LDL
      cholesterol (r = -0.309; p < 0.05); and sTNF-R II correlated with total
      cholesterol and LDL-cholesterol (r = 0.311 and r = 0.316; p < 0.05). The serum
      concentrations of TNF-alpha are increased in patients with CAD, but this does not
      reflect the clinical state of patients. In pts with stable angina these increased
      levels of TNF-alpha may be accompanied with higher concentrations of sTNF-R I--it
      seems to be the compensatory mechanism in long-term atherosclerosis. Lipid
      disturbances may influence the cytokines metabolism in pts with CAD.

PMID- 11579826
TI  - [The assessment of nutritional status in children with chronic hepatitis B
      treated with interferon alpha].
AB  - The aim of the study was an evaluation of nutrition status in children with
      chronic hepatitis B during IFN-alpha therapy. Observation was carried out in a
      group of 40 children in the age range of 1-14 years with clinically, diagnosed
      chronic hepatitis B. Respectful of age 2 subgroups were distinguished. I: 27
      children up to 4 years old, II: 13 children in the age range of 4-14 years. The
      nutritional status was evaluated by anthropometric measurement (body mass, body
      length/height). Moreover Cole index was estimated at the beginning and completion
      of the treatment and in the time of the highest weight loss. None of the examined
      children has body mass deficiency before IFN-alpha treatment: Cole index was in
      normal range as well. Lack of appetite, connected with IFN-alpha administration,
      was observed in 42.5 children during therapy. Weight loss was observed in 65% of
      the examined children especially in the first 2 months of therapy. Return to the
      initial body mass value was observed within 3 months after IFN-alpha completion
      in 77% children; but in 2 children only 12 months after IFN-alpha therapy
      termination. 12 months after IFN-alpha completion Cole index lower than initial
      was observed in 42.5% of the examined children in spite of return of body mass to
      initial values. There was no observed unfavourable influence of IFN treatment on
      body height. 20-weeks IFN-alpha therapy in children with chronic hepatitis B
      often causes lack of appetite, which may lead to reversible disturbances in
      nutritional status. Correct dietetic proceeding is necessary to decrease the
      frequency and intensity of disturbances in nutritional status in this group of
      children.

PMID- 11579827
TI  - [The use of flow cytometry for the determination of the hepatitis B virus pre-S1
      envelop protein binding by human peripheral blood lymphocytes in vitro in the
      course of recovery].
AB  - The course of hepatitis B virus (HBV) infection depends on the host immune
      response to various antigens of the virus, including hepatitis B surface antigen
      (HbsAg), which is present on the envelope of HBV and which contains Pre-S1, Pre
      S2 and S proteins. The peripheral blood lymphocytes (PBL) from patients with
      chronic hepatitis B infection (CHB) and patients acutely infected with HBV and
      recovered completely (convalescents) were studied for detecting of Pre-S1 antigen
      binding. We used a cytometric method for measurement of the binding of
      fluorescein labeled Pre-S1 antigen (FITC/Pre-S1) to the PBL. The binding of
      FITC/Pre-S1 was determined on resting lymphocytes and on lymphocytes cultured in
      vitro for 5 days in the presence of Pre-S1 and phytohaemagglutinin-P (PHA-P). The
      expression of CD3 and CD19 molecules on the surface of PBLs simultaneously with
      the expression of FITC/Pre-S1 was also analysed using flow cytometry. We found
      that the Pre-S1 binding significantly depends on the state of the activation of
      lymphocytes. Specific stimulation of the convalescent lymphocytes with Pre-S1
      resulted in an increase in the percentage of the FITC/Pre-S1 binding cells in
      relation to the unstimulated cultured and resting cells as well as to the cells
      from CHB patients. We suggest that flow cytometric measurement of Pre-S1 binding
      by lymphocytes may be useful indicator of the disease activity.

PMID- 11579828
TI  - [Urinary excretion of Tamm-Horsfall protein, albumin and beta-2 microglobulin in
      children with recurrent urinary tract infection].
AB  - In the study 27 children after urinary tract infection (UTI) and 28 healthy
      children were examined. Vesico-uretic reflux in 10 patients, and in 17 normal
      urinary excretion were diagnosed. In 11 children the family history was
      documented. The 17 healthy controls were siblings of children with normal urinary
      excretion. In all children urinary excretion of albumin, beta 2-microglobulin and
      Tamm-Horsfall protein (THP) were examined. Children with UTI both with and
      without urinary obstruction show the increased urinary excretion of THP as
      compare with healthy children. Healthy siblings of children with UTI show
      increased urinary concentration of THP as compared with healthy controls. In both
      examined groups of children with UTI, function of glomeruli, procimal and distal
      tubuli measured by urinary excretion of albumin, beta 2-microglobulin and THP
      were normal.

PMID- 11579829
TI  - [Von Willebrand factor in hemodialysed patients with chronic renal failure].
AB  - The aim of the work was to evaluate the von Willebrand factor antigen (vWF Ag)
      concentration in the blood plasma of hemodialysed patients with chronic renal
      failure. The study was performed in the group of 43 patients (means aged 42.8
      years) with chronic renal failure dialysed means 4 hours 3 times a week. The
      blood was obtained before and after hemodialyze and in 11 patients additionally
      after 1 year of systematic hemodialyze. The control group consisted of 51 healthy
      volunteers means aged 35.6 years. In the citric blood plasma concentration of vWF
      Ag was determined using immunosorbed enzyme-linked assay (ELISA). In the blood
      plasma of patients with chronic renal failure significantly higher concentration
      of vWF Ag than in controls was observed. 4-hours and 1-year dialyze did not
      influence the level of vWF Ag in patients with chronic renal failure.

PMID- 11579830
TI  - [The value of the ultrasonography and computed tomography in diagnosis and
      monitoring of treatment of renal abscesses in children].
AB  - A retrospective study of 14 patients from 2 to 13 years old with renal abscess
      was performed. We evaluated the diagnostic value of ultrasonography (US) and
      computed tomography (CT) in diagnostic investigation and treatment of renal
      abscess, which have changed during the past ten years from classic surgical
      treatment to percutaneous drainage. US and CT have revealed the diagnosis by
      showing a hypoechogenic or hypodense mass in all 14 patients. All had an
      intensive course of antibiotic treatment. In 10 of them the abscess were drained
      percutaneously by US guided drainage. Percutaneous drainage was unsuccessful in 2
      patients, who subsequently underwent classic surgical exploration, incision and
      drainage for uncontrolled infection. We conclude that US and CT greatly
      facilitate the diagnosis and permit the percutaneous drainage of renal abscess in
      paediatric age group, which benefits from this minimally invasive therapy.

PMID- 11579831
TI  - [Chronic viral hepatitis C in patient with Hand-Schuller-Christian disease].
AB  - Chronic hepatitis C often occurs among patients with different diseases and may
      influence their natural history. From the other hand coexisting diseases may
      modify the hepatitis C infection. We present a case of a male patient with the
      histiocytosis X, earlier called Hand-Schuller-Christian disease with hepatitis C
      virus infection. The mild course of the chronic hepatitis C, not requiring anti
      viral therapy, may be the result of immunomodulation relevant to Hand-Schuller
      Christian disease.

PMID- 11579832
TI  - [Genetic basis of cardiac diseases leading to heart failure].
AB  - In the last few years medical genetics is assuming a much more prominent position
      in the etiology of cardiac diseases. The article presents the current state of
      the molecular and genetic basis of diseases leading to heart failure, such as
      coronary artery disease, idiopathic cardiomyopathy, valvular abnormalities,
      essential hypertension and other rare cardiac diseases. Looking for the molecular
      basis is followed by practical advice on the role of genetic testing, expanding
      of the methods of prophylaxis, modification of medical managing and treatment.

PMID- 11579833
TI  - [Measurement dispersion of the QT interval and its significance in different
      diseases].
AB  - QT dispersion reflects in homogenecity of ventricular repolarization. It is
      calculated using 12-leads standard synchronized ECG or 24-hours Holter
      monitoring. The most common used indicators are: QT dispersion (QTd), based on
      Bazett's formula corrected for heart rate QT dispersion (QTcd) and QT dispersion
      ratio (QTdR). QT apex and QTd corrected for total number of leads ECG in which QT
      interval was counted are rare used. Increased QT dispersion is observed among
      others: following myocardial infarction (MI), coronary heart disease (CAD),
      hypertension, chronic heart failure (CHF), long QT syndrome, as well as diabetes.
      Following mentioned diseases increased QT dispersion has prognostic value for
      sustained ventricular tachycardia. Dispersion of repolarization > or = 80 ms
      after MI is a risk factor for sudden cardiac death. Following acute MI decrease
      of QT dispersion after successful thrombolytic therapy is observed and its value
      > or = 100 ms is regarded as a marker of reperfusion insufficiency. QT dispersion
      in patients with CAD correlates with extent of ischemia and decreases after
      coronary angioplasty (PTCA). In recent years beneficial effect of angiotensin
      converting enzyme inhibitors and beta-adrenolytic therapy on QT dispersion was
      described. Actually the improvement of computerised methods in assessment of QT
      dispersion is observed, but it require further investigations.

PMID- 11579834
TI  - [Selected independent risk factors of atherosclerosis in children as the basis of
      early detection of premature ischemic heart disease].
AB  - This review briefly summarises the scientific evidence for the child's future
      risk of ischemic heart diseases (IHD). The conventional risk factors such as
      dyslipidemia, hypertension, diabetes and smoking can not account for all the
      cases of cardiovascular diseases. Therefore other risk factors such as
      fibrinogen, homocysteine, paraoxonaze and abnormality in antioxidant defence
      systems are included. Among the lipids parameters the level of lipoprotein (a)
      and increased plasma cholesterol, specifically LDL-cholesterol may be used as a
      marker of family history of IHD and hypercholesterolemia. Additionally, low level
      of HDL-cholesterol is also related with endothelial dysfunction and increased
      oxidative stress. It has been hypothesised that free radicals mediate in the
      development of IHD and that antioxidants play a protective role in prevention of
      this pathology. Many of the major risk factors can be modified through diet, body
      mass control, exercise and (if necessary) through pharmacological intervention.
      Therefore, the efficacious prevention should be related with the early detection
      of risk factors particularly in children with familial dyslipidemia, hypertension
      and IHD.

PMID- 11579835
TI  - [The role of cytokines in cardiovascular diseases].
AB  - Cytokines are the regulatory peptides produced, excreted and influencing function
      of many cells types in human including endothelium and cardiomyocytes. This is
      why their role in the etiopathology of cardiovascular diseases is so important
      and new discoveries confirm their contribution to it. Cytokines worsen the
      outcome of heart failure, intensify remodeling of vascular wall after PTCA and
      provoke instability of atherosclerotic plaque. On the other hand some of their
      properties like ability to force neovascularisation in the ischaemic parts of
      heart are already used in clinical trials. New discoveries considering cytokines
      are sure to bring us near to better understanding of their role in cardiovascular
      disease pathology and new ways of therapy.

PMID- 11579836
TI  - [Tachycardia-induced cardiomyopathy].
AB  - Dilated cardiomyopathy induces circulatory insufficiency with poor prognosis.
      Persistent tachyarrhythmias may be the cause of this disease. At particular high
      risk for heart damage and insufficiency are young people and children. The group
      of most dangerous arrhythmias consist of: incessant tachycardia in patients with
      preexcitation syndrome and supraventricular tachyarrhythmias (atrial flutter and
      fibrillation, ectopic atrial tachycardia) with high rate of ventricles. The
      result of arrhythmias is dilatation of the heart and thinness of ventricular
      walls with hemodynamic disorders. The effective therapy of arrhythmias--ablation
      of the accessory pathway in patients with pre-excitation syndrome or reversion to
      sinus rhythm (pharmacological or electric cardioversion) in patients with atrial
      fibrillation and flutter, often leads to normalisation of heart ejection function
      and diameter. Therefore it exist important question: is dilated cardiomyopathy
      the cause or consequence of tachyarrhythmias? Causative antiarrhythmic therapy in
      these second cases gives a possibility to improve the prognosis in patients with
      such a disease.

PMID- 11579837
TI  - [Physiology and mechanisms of blood circulation in vascular bed].
AB  - The Authors have presented the essential physiological aspects of the blood flow
      vital to all physicians considering use of the autohaemotransfusion,
      extracorporeal circulation, extrapulmonary oxygenation and controlled
      haemodilution.

PMID- 11579838
TI  - [Doppler myocardial velocity gradient as a new diagnostic index for the
      assessment of myocardial disease].
AB  - Currently, echocardiography is the technique of choice in the noninvasive
      assessment of left ventricular (LV) function. Unlike the assessment of LV
      systolic function, its role is limited in the quantification of LV diastolic
      function where only global LV filling can be assessed. Tissue Doppler
      echocardiography (TDE) is a recently introduced imaging technique which allows
      for direct assessment of LV myocardial contraction and relaxation. Therefore,
      parameters derived from TDE showed provide a more accurate assessment of LV
      systolic and diastolic function. Doppler myocardial velocity gradient (MVG) is a
      new parameter derived from TDE, which enables the measurement of the spatial
      distribution of transmyocardial velocities over the cardiac cycle. The most
      studied application of this technique relates to the earlier and more sensitive
      diagnosis of different forms of cardiomyopathy. Based on the Doppler MVG
      measurement, patients with ischaemic cardiomyopathy can be differentiated from
      those with idiopathic dilated cardiomyopathy. In both diseases MVG is reduced in
      systole, but as opposed to dilated cardiomyopathy, MVG in patients with ischaemic
      cardiomyopathy is also markedly reduced in early diastole. MVG derived from TDE
      also provides new diagnostic insights into genetically determined heart muscle
      diseases. It has been shown that an early diastolic MVG < or = 7 s-1 is
      characteristic for patients with hypertrophic cardiomyopathy and differentiates
      this group of patients from 'athletes' heart, independently of the degree of LV
      hypertrophy. A recent study has also shown that in Friedreich ataxia related
      cardiomyopathy there is a close relation between the degree of genotype
      abnormalities and the degree of reduction in the MVG. Also, the assessment of
      Doppler MVG enables the differentiation of restrictive cardiomyopathy from
      constrictive pericarditis. Based on available literature it appears that TDE
      derived MVG enhances the information available from conventional echocardiography
      and helps to establish an earlier diagnosis in patients with primary and
      secondary myocardial diseases.

PMID- 11579839
TI  - [The risk of direct current countershock].
AB  - Direct current cardioversion (DCC) is a procedure commonly used to restore the
      sinus rhythm in patients with supraventricular and ventricular arrhythmias. Its
      safety, regarding the use of electric current, is still a matter of controversy
      and debate. The patients with atrial fibrillation/flutter, supraventricular or
      ventricular tachycardia represent a broad spectrum of clinical conditions and it
      is difficult to draw the conclusions. The high success rate of DCC in restoring
      the sinus rhythm, may be partly responsible for enhancing and revealing
      proarrhythmic properties of antiarrhythmic drugs. The deaths described as a
      complications of DCC were mainly due to the proarrhythmia and less common to the
      progression of the pathologic process. The embolic, arrhythmic and anesthetic
      complications of DCC can be prevented if the known recommendations of performing
      the DCC are followed. The authors review critically the literature data about the
      complications of the procedure and come to the conclusion of safety of DCC.

PMID- 11579840
TI  - [Calcium channel blockers in the treatment of cardiovascular disease].
AB  - Drugs classified as calcium channel blockers (CHBs) are now among the most
      frequently prescribed drugs for the treatment of cardiovascular disease. Although
      the currently available CCBs have major differences in their structural and
      cardiovascular effects, they share the common property of blocking the
      transmembrane flow calcium ions through voltage gated L-type channels. These
      drugs have been approved for the treatment of hypertensive heart disease: they
      reduce left ventricular hypertrophy and improve its sequelae, such as ventricular
      dysrhythmias, impaired filling and contractility, and myocardial ischemia. Long
      acting CCBs have been shown to reduce mortality and morbidity in elderly patients
      with systolic hypertension, appear to be extremely useful in patients with
      cyclosporin-induced hypertension, and can be used as alternatives to ACE
      inhibitors in patients with hypertension and concomitant diabetes mellitus, renal
      disease, Raynaud's phenomenon or migraine. Long-acting dihydropyridine have been
      shown to be effective and safe in the treatment classic angina pectoris and
      vasospastic angina, supraventricular arrhythmias, particularly reentrant AV-nodal
      tachycardia, others to be beneficial in patients with congestive heart failure,
      and all of them have potential for decreasing atherogenesis.

PMID- 11579841
TI  - [The significance of cathepsins B and D and their inhibitors in cancer disease].
AB  - Cathepsins play an important role in the pathogenesis of the great number of
      cancer diseases i.e. in breast, head and neck, liver, pancreas, colon and skin
      cancer. Estimation of cathepsins activity referring to different kinds of cancer
      diseases has a significance both in diagnostics and in monitoring of their
      running. An essential role in cancer disease development is also reported for
      cathepsins B and D inhibitors. Using drugs that are able to inhibit the harmful
      activity of cathepsins, would give a chance to supplement an anti-cancer therapy
      with the new agents. In future, it could increase the efficiency of cancer
      treatment in a significant way.

PMID- 11579842
TI  - [The role of collagen in the process of renal fibrosis].
AB  - The progression of chronic renal failure results from the process of fibrosis,
      which involves the proliferation of renal fibroblasts and the secretion of
      extracellular matrix proteins (ecm) by these cells. Collagen is the main
      component of ecm. Renal collagen types in normal kidney and in renal diseases
      were described. Mediators that stimulate fibroblast proliferation, collagen
      turnover and factors its regulating were discussed.

PMID- 11579843
TI  - [Chronic allograft nephropathy].
AB  - In spite of improved one year renal allograft survival long-term results of renal
      transplantation did not change since several years. Progressive decline of graft
      function developing few years after renal transplantation remains a significant
      problem in renal replacement therapy. The clinical manifestation of progressive
      impairment of the kidney transplant is heterogeneous and the differential
      diagnosis of chronic graft rejection is difficult, even if histopathological
      examination is performed. Improvement of immunosuppressive therapy and avoidance
      of nonimmunologic factors which increase the risk of graft failure seem to
      influence markedly function of kidney grafts.

PMID- 11579844
TI  - [Diagnostic possibilities of anal endosonography in proctology. Part II].
AB  - In the second part of the paper, we present advantages and drawbacks of transanal
      endosonography with the use of axial endoprobe in the diagnostics of perianal and
      perirectal abscesses and fistulas and also for tumours of the rectum. Typical
      images of the fistula nad abscess were shown. Ultrasonographic staging for the
      rectum malignancies was presented together with possibilities of assessment
      perirectal lymph nodes involvement by ultrasonography. Diagnosis of local
      recurrence by anal endosonography was presented and compared with other methods.

PMID- 11579845
TI  - Powered endoscopic inferior meatal antrostomy under canine fossa telescopic
      guidance.

PMID- 11579846
TI  - A unique complication of microflap surgery of the vocal fold.

PMID- 11579847
TI  - Mixed (external) laryngocele.

PMID- 11579848
TI  - The sinusoidal vertical-axis rotation test.

PMID- 11579849
TI  - Localized laryngotracheobronchial amyloidosis: case report and review of the
      literature.
AB  - Although localized laryngotracheobronchial amyloidosis is rare, the
      otolaryngologist--head and neck surgeon should be familiar with this condition.
      Its characteristic appearance can suggest its presence in a patient who has the
      typical initial symptoms. Biopsies during direct laryngoscopy and bronchoscopy
      can play both a diagnostic and therapeutic role. After an appropriate examination
      to rule out systemic involvement, the patient should be managed with conservative
      surgery, although the use of a CO2 laser might be more efficacious than
      conventional surgery. With appropriate diagnosis and treatment, patients should
      expect a favorable prognosis. In this article, we describe a new case of
      localized laryngotracheobronchial amyloidosis in a 67-year-old woman, and we
      review the literature on this subject.

PMID- 11579850
TI  - Combined temperature-controlled radiofrequency tongue reduction and UPPP in apnea
      surgery.
AB  - The objective of this study was to investigate the effects on outcomes and
      morbidity of combining temperature-controlled radiofrequency (TCRF) tongue
      reduction with uvulopalatopharyngoplasty (UPPP) as an initial site-directed
      approach to the surgical treatment of obstructive sleep apnea syndrome (OSAS).
      This investigation was a prospective, nonrandomized, open-enrollment study of 20
      consecutive eligible patients with OSAS. Seven patients had a single-level
      velopharyngeal obstruction (Fujita type I or IIa), and they were assigned to
      undergo UPPP only (group 1). Thirteen patients had a multilevel velopharyngeal
      and retroglossal obstruction (Fujita type IIb), and they were assigned to undergo
      TCRF tongue reduction in addition to UPPP (group 2). Patients who had only a
      retroglossal obstruction (Fujita type III) were not included in this study.
      Following their initial operation, nine patients in group 2 underwent two
      subsequent in-office TCRF tongue treatments under local anesthesia. Three
      patients in group 2 were lost to followup, and one patient underwent only one
      TCRF procedure at the initial operation; data on the latter patient are included
      in some of the outcomes measures reported here where indicated, but no data are
      reported on the three who were lost to followup. The primary post-treatment
      outcomes measures were the results of comparative polysomnography and clinician
      and patient evaluations regarding morbidity and symptom improvement. Analysis of
      these data showed that there was no difference between the two groups in terms of
      postoperative pain or dysphagia following the initial operative session. The
      degree of symptom improvement in the two groups was similar. Overall success
      rates--as measured by the apnea/hypopnea index (group 1: 57.1% success; group 2:
      50.0%) and by the apnea index (group 1: 71.4% success; group 2: 70.0%)--were
      statistically comparable, given the small size of the sample (figures are based
      on 10 patients in group 2). The author concludes that combining TCRF tongue
      reduction with UPPP in patients with multilevel obstruction improves response
      rates to a degree that is comparable to that seen with UPPP alone in patients
      with single-level velopharyngeal obstruction. Moreover, the combination treatment
      does not increase the risk of additional pain, morbidity, and complications
      compared with UPPP alone.

PMID- 11579851
TI  - Use of adenoidectomy and adenotonsillectomy in children with otitis media with
      effusion.
AB  - We conducted a prospective study of 48 children, aged 2 to 14 years, who had
      persistent bilateral otitis media with effusion, enlarged adenoids, and a
      bilateral conductive hearing loss. Half of these patients underwent adenoidectomy
      and the other half adenotonsillectomy. All patients were followed every 2 weeks
      for up to 6 months. At 2 months postoperatively, the overall success rate in
      terms of the resolution of middle ear effusion was 85.1%. Success rates were
      82.6% in the adenoidectomy group and 87.5% in the adenotonsillectomy group; the
      difference was not statistically significant. Our findings demonstrate that both
      adenoidectomy and adenotonsillectomy are effective for the treatment of
      persistent otitis media with effusion, and they confirm the findings of other
      studies. Based on our findings and those of other investigators, we offer a four
      step approach to the management of these children.

PMID- 11579852
TI  - Sudden hypoacusis treated with hyperbaric oxygen therapy: a controlled study.
AB  - The term sudden hypoacusis describes a hearing loss of rapid onset and unknown
      origin that can progress to severe deafness. Of the many therapeutic protocols
      that have been proposed for treating sudden hypoacusis, hyperbaric oxygen therapy
      (HOT) plays a leading role. We studied 50 patients who had been referred to our
      ENT unit within 48 hours of the onset of sudden hypoacusis. We randomly assigned
      30 of these patients to undergo once-daily administration of HOT for 10 days; the
      other 20 patients were treated for 10 days with an intravenous vasodilator.
      Response to therapy in all patients was evaluated by calculating the mean hearing
      threshold at frequencies between 500 and 4,000 Hz and by assessing liminal tonal
      audiometry results recorded at baseline and 10 days after the cessation of
      treatment. These results, plus the findings of other audiologic and otoneurologic
      examinations, revealed that the patients in the HOT group experienced a
      significantly greater response to treatment than did those in the vasodilator
      group, regardless of age and sex variables. Significantly more patients in the
      HOT group experienced a good or significant response. In both groups, patients
      with pantonal hypoacusis responded significantly better than did those with a
      milder condition. Based on our findings, coupled with the fact that oxygen
      therapy is well tolerated and produces no side effects, we conclude that HOT
      should be considered the preferred treatment for patients with sudden hypoacusis.

PMID- 11579853
TI  - Endoscopic removal of an ectopic third molar obstructing the osteomeatal complex.
AB  - We report a rare case of an ectopic third molar at the level of the osteomeatal
      complex. A 21-year-old man came to us with a left-sided nasal obstruction of 2
      years' duration. Computed tomography of the paranasal sinuses revealed that an
      aberrant tooth was obstructing the osteomeatal complex and bulging into the
      ethmoid infundibulum. Opacity of the entire left maxillary sinus indicated the
      presence of an associated cystic formation. A transnasal endoscopic sinus
      technique was employed to create a large middle meatal antrostomy and to remove
      the tooth as well as the cystic contents and cyst wall. Pathologic analysis
      revealed that the cyst was dentigerous. After recovery from surgery, the patient
      resumed nasal breathing. The endoscopic surgical approach used in this case
      caused less morbidity than do the more common methods (e.g., the Caldwell-Luc
      procedure) of removing ectopic teeth from the sinus.

PMID- 11579854
TI  - A case of parotid mucoepidermoid carcinoma complicated by fatal gastrointestinal
      bleeding.
AB  - Mucoepidermoid carcinoma is one of the most common of the salivary gland
      neoplasms. Histologically, it is classified as either a low-, intermediate-, or
      high-grade tumor, and there are significant differences in prognosis among the
      different grades. Patients with low-grade disease have an excellent chance of
      survival. High-grade tumors behave aggressively, and they frequently manifest as
      local recurrences and distant metastases. We describe a case of a high-grade
      mucoepidermoid carcinoma of the parotid gland that had metastasized to the skin,
      stomach, and liver. The disease culminated in a rapidly fatal bleeding from the
      stomach metastasis. Such a complication is unusual and to our knowledge has not
      been previously reported. We briefly discuss the clinical features, biologic
      behavior, and treatment of this tumor.

PMID- 11579855
TI  - First cases of a pestilence more malignant.

PMID- 11579856
TI  - Taking the HIV factory tour.

PMID- 11579857
TI  - Clinical features and T-cell subsets in HIV-infected children with and without
      lymphocytic interstitial pneumonitis.
AB  - Lymphocytic interstitial pneumonitis (LIP) is a non-infective lung condition
      common in untreated older children with vertically acquired HIV infection. Little
      is known about the prognosis in children with LIP, and diagnosis remains a
      problem where lung biopsy is not feasible. Our aim was to determine which
      clinical features aid the diagnosis of LIP in conjunction with the typical
      reticulonodular radiological picture, and whether the prognosis in children with
      LIP is different from that in HIV-infected children of the same age without LIP.
      We retrospectively compared the clinical features and T-cell subsets of 49
      children with LIP with those of 56 children of similar age without LIP. Diagnosis
      of LIP was made radiologically. All children were apyrexial at the time of X-ray
      and acute intercurrent infections and tuberculosis had been excluded as far as
      possible. Ages ranged from 24 to 112 months in the non-LIP group and from 24 to
      120 months in the LIP group. Digital clubbing and reticulo-endothelial
      hyperplasia were significantly more common in children with LIP than in those
      without. Children with LIP tended to have lower CD4+ counts and CD4% and higher
      CD8+ counts and CD8%, which resulted in significantly lower CD4/CD8 ratios in
      children under 5 years with LIP. It is possible in most cases to diagnose LIP
      using a combination of clinical and X-ray findings, as long as every effort is
      made to exclude tuberculosis. Lower CD4+ counts and CD4% as well as more frequent
      hospital admissions suggest that LIP adversely affects prognosis in children with
      HIV.

PMID- 11579858
TI  - Growth in early childhood in a cohort of children born to HIV-1-infected women
      from Durban, South Africa.
AB  - This study describes growth in a cohort of black South African children born to
      HIV-1-infected women in Durban. Children born to HIV-1-seropositive women were
      followed up from birth to early childhood. At birth and at each visit, growth
      parameters were measured. Mean Z-scores were calculated for weight-for-length,
      weight-for-age and length-for-age and, if they were low, the children were
      regarded as wasted, malnourished or stunted, respectively. At the end of the
      study, there were 48 infected and 93 uninfected children. There were no
      significant differences between the two groups at birth. Thereafter, the infected
      group was found to have early and sustained low mean Z-scores for length-for-age
      and weight-for-age but not for weight-for-length. The means reached significance
      at ages 3, 6 and 12 months for length and at 3, 6 and 9 months for weight.
      Infected children who died early had more severe stunting, wasting and
      malnutrition than infected children who survived. Infected children born to HIV
      positive women have early and sustained stunting and are malnourished but not
      wasted. Children with rapidly progressive disease have both stunting and wasting
      and are more severely affected. Early nutritional intervention might help prevent
      early progression or death in HIV-infected children, particularly in developing
      countries without access to anti-retroviral therapy in state hospitals.

PMID- 11579860
TI  - Paralytic poliomyelitis associated with the Sabin 3 revertant strain of
      poliovirus in Bahrain.
AB  - We report a case of vaccine-associated paralytic poliomyelitis (VAPP) in Bahrain.
      The case occurred in an 8-week-old infant who had received a dose of oral polio
      vaccine (OPV) 7 days after birth. She was in contact with two vaccinees who had
      received OPV during the national immunisation campaign conducted 10 days before
      her birth. Specimens from the infant were sent to the WHO Collaborating Centre
      for Virus Reference and Research Laboratory for serological testing and virus
      detection, including genomic sequencing. Clinical and virological features are
      presented of a case of VAPP caused by the Sabin 3 strain of poliovirus that had
      reverted towards neurovirulence. The case represents one in 51,879 first doses of
      OPV distributed between 1995 and 1998. In order to reduce further the risk of
      VAPP, the dose of OPV at birth has been discontinued and a sequential schedule of
      inactivated polio vaccine (IPV) followed by OPV will be recommended.

PMID- 11579859
TI  - A randomised, double-blind, placebo-controlled clinical trial of vitamin A in
      severe malaria in hospitalised Mozambican children.
AB  - This paper reports a randomised, double-blind, placebo-controlled clinical trial
      of the effect of routine vitamin A supplementation given on admission to children
      with severe malaria with regard to survival, recovery during hospitalisation and
      outcome 6 weeks after discharge. Children aged between 6 and 72 months admitted
      to the paediatric wards of the Central Hospital of Maputo (CHM), Mozambique with
      a diagnosis of severe malaria were randomly assigned either to a control group
      (placebo) or an experimental group (vitamin A) and were followed up 6 weeks after
      discharge. There were 280 children in the experimental and 290 in the placebo
      group. Seven (2.5%) and 13 (4.5%) children died in the experimental and the
      placebo groups, respectively, a relative risk of death of 0.56 (95% CI 0.23-1.38,
      p = 0.201). During the 1st 5 hours of admission, the relative risk of death in
      the vitamin A-supplemented group was 2.54 (0.50-12.96); after 5 hours of
      admission it was 0.19 (95% CI 0.04-0.85; p = 0.015). In the supplemented group,
      4/82 (4.9%) of the children developed neurological sequelae vs 2/78 (2.6%) in the
      placebo group (RR = 1.90; 95% CI 0.36-10.09; p = 0.682). Although the overall
      reduction in the risk of death observed for all children receiving vitamin A is
      not statistically significant, it might be clinically important. This finding
      cannot, however, be accepted as a firm conclusion and requires validation by
      future trials.

PMID- 11579861
TI  - Haemophilus influenza type b vaccine in Israel: experience in a paediatric
      ambulatory clinic.
AB  - In Israel, vaccination are the overall responsibility of the government. We were
      the first in Israel to give the Hib (Haemophilus influenza type b) vaccine to the
      population, through independent means, without government control. The aim of the
      study was to follow longitudinally the specific group of children vaccinated in
      our ambulatory clinic. In this study, 1,497 children between 2 and 52 [mean (SD)
      13 (9)] months of age at the time of first vaccination were vaccinated with Hib
      vaccine. Over the next 7 years, they were followed up by repeated phone calls
      when parents were asked about hospitalisation and any serious infectious
      diseases. Of the 1,497, 1,444 were followed during the years 1992 to 1999 and 36
      were hospitalised during this time. All blood and cerebrospinal fluid cultures
      were negative. No proven case of Hib infection could be demonstrated. Despite the
      small sample size, this study justifies the continued use of the vaccine along
      with maintaining surveillance for Hib infection.

PMID- 11579862
TI  - An epidemiological survey of cystic echinococcosis among Tibetan school pupils in
      West China.
AB  - Human cystic echinococcosis (CE) caused by infection with a larval stage of
      Echinococcus granulosus is a serious public health problem in West China. Because
      CE is a zoonosis, dogs and livestock are important hosts in transmission.
      Tibetans, especially teenagers, have a natural relationship with these definitive
      and intermediate hosts in West China and although some areas of Tibet are
      therefore CE-endemic, few, if any, detailed community studies have been reported.
      A total of 451 Tibetan school pupils living in rural Tianzhou County in Gansu
      Province in West China were investigated by mass ELISA and IHA with ultrasound
      scanning back-up, and positivity rates were found to be 9.5% and 1.6%,
      respectively, with 0.98% confirmation of hepatic CE in four asymptomatic cases.
      Seropositivity rates varied with age between 6.2% and 13.2%. IHA found that
      females had a significantly greater risk of infection than males, a ratio of
      about 3:1. Age-specific immunopositive rates increased from 6.2% in the 8-13
      years age group to 13.2% in those aged over 18. The study found that keeping dogs
      and herding animals had no effect on rates of infection but that the number of
      sheep owned by a family correlated with infection rates. The rate of infection in
      people who hunted was significantly higher than in those who did not. Level of
      education was found to have no effect on rates of infection.

PMID- 11579863
TI  - Incidence of childhood accidents determined in a study based on home surveys.
AB  - A retrospective survey of accidents during a 12-month period was carried out at
      Vila Lobato in the town of Ribeirao Preto, Brazil using home surveys involving
      25% of residences in this area. Variables relating to the accidents and data
      concerning the children involved were analyzed, i.e. sex, age, type of accident,
      place of occurrence, time of day, time of year, which part of the body was
      involved and the person accompanying the victim of the accident. There were 260
      accidents during the year, mainly involving the 1-5-year (41.1%) and 5-10-year
      (33.1%) age ranges. The most frequent accidents were falls (46.9%), contusions
      (26.5%) and cuts (11.9%). Most accidents occurred at home (65.7%), followed by in
      the street (25.4%) and at school (6.1%). More accidents occurred in the late
      afternoon (49.6%) and during the summer months and school holidays (38.1%) than
      at other times. The lower limbs were the sites most often involved (36.9%),
      followed by the upper limbs (32.3%) and the head (25.4%). Most children (75.7%)
      were accompanied when they suffered an accident. Slightly more boys (55.4%) than
      girls (44.6%) had accidents. Statistical analysis of the results by the chi 2
      test showed significant differences for all variables studied with respect to the
      occurrence of accidents (p < 0.05), except gender. The authors discuss the need
      to expand the debate on accidents and for the application of knowledge to prevent
      them occurring.

PMID- 11579864
TI  - Emergence of multi-drug-resistant Acinetobacter anitratus species in neonatal and
      paediatric intensive care units in a developing country: concern about
      antimicrobial policies.
AB  - Antimicrobial abuse is a serious risk factor for the emergence of multi-drug
      resistant (MDR) pathogens. We report on the emergence of multi-drug-resistant
      Acinetobacter anitratus species over two 8-week periods in 1999 in the neonatal
      and paediatric intensive care units (NICU and PICU) of King Edward VII Hospital,
      Durban, South Africa. The source, transmission dynamics, microbiological
      evaluations, antibiotic utilization patterns and outcome were evaluated. MDR
      Acinetobacter anitratus was isolated from different body sites in 23 infants less
      than 2 months of age, 18 in the PICU and five in the NICU. The mortality was
      56.5% and two survivors required re-admission. Ten of the 23 cases had entered
      the ICU with MDR Acinetobacter anitratus. Eleven of the study infants had
      received broad-spectrum antimicrobial agents before entering the ICU, while all
      infants with nosocomially acquired MDR Acinetobacter anitratus had received broad
      spectrum antimicrobial agents. All the surgical cases with MDR Acinetobacter
      anitratus died. Microbiological data from both ICUs for 1999 indicated that gram
      negative bacteria accounted for two-thirds of isolates, Acinetobacter anitratus
      and Klebsiella pneumoniae accounting for 33% and 27% of the isolates,
      respectively. Only 53% and 57% of all Acinetobacter spp isolates were susceptible
      to piperacillin/tazobactam and carbepenems, respectively. MDR Acinetobacter
      anitratus is an emerging problem to which antimicrobial abuse contributes.

PMID- 11579865
TI  - Respiratory syncytial virus subgroup A in hospitalized children in Zarqa, Jordan.
AB  - The epidemiology of RSV infection was investigated in 271 children aged less than
      2 years admitted to the Zarqa Government Hospital, Jordan with bronchiolitis or
      bronchopneumonia. Nasopharyngeal washings were cultured and RSV antigen was
      detected by the direct immunofluorescence technique. Of the 271 specimens, 69
      (25.46%) were positive for RSV, representing 50.36% of the respiratory viruses.
      All RSV isolates were typed as subgroup A by monoclonal antibody and confirmed by
      RT-PCR. RSV was prevalent in the hospitalised children in the coldest months of
      the year. The epidemics began in January or February, peaked in spring and then
      disappeared in summer. This study supports the idea that RSV subgroup A is a
      major contributor to winter outbreaks of respiratory tract disease in children,
      and health care workers in Jordan should consider the diagnosis during January
      May each year.

PMID- 11579866
TI  - The Ibadan conjoined twins: a report of omphalopagus twins and a review of cases
      reported in Nigeria over 60 years.
AB  - An omphalopagus set of female conjoined twins, undiagnosed prenatally, who
      presented as obstructed labour needing operative delivery is reported. Their
      anatomic characteristics and clinical features, including overwhelming sepsis in
      twin II which forced early separation, and those which led to their demise are
      described. Twelve other cases reported in Nigeria over the past 60 years are
      reviewed with reference to the aetiology and epidemiology of conjoined twinning
      and the determinants of successful surgical separation.

PMID- 11579867
TI  - Myoclonic seizure following intravenous verapamil injection: case report and
      review of the literature.
AB  - An 18-month-old girl with supraventricular tachycardia was given a dose of
      intravenous verapamil and suffered a short myoclonic seizure which occurred again
      when she was given second and third doses. In the absence of any predisposing
      factors, direct drug reaction was implicated as the cause of the seizure.

PMID- 11579868
TI  - Anal injury and fissure-in-ano from sexual abuse in children.
AB  - Ano-rectal injuries in children are generally uncommon, and those caused by
      sexual abuse are rarely reported in our environment. This is a report of two
      children aged 5 and 12 years who sustained anal injuries following anal sexual
      abuse. Both presented late with fissure-in-ano and were managed conservatively.
      Though fissure-in-ano is not uncommon in children, it might be necessary to
      exclude sexual abuse and undertake appropriate evaluation and treatment. The
      child must be protected from further abuse.

PMID- 11579869
TI  - Accidental detection of lupus anticoagulants in children.
AB  - During routine pre-operative evaluation, a 6-month-old infant and an 11-year-old
      girl were found to have prolonged activated partial thromboplastin time with
      positive lupus anticoagulants. Both children underwent successful cardiac surgery
      and had no thrombotic or bleeding complications. A literature search revealed
      that positive lupus anticoagulants can follow minor infections in otherwise
      asymptomatic children and are benign and self-limiting. A minority, however, can
      develop bleeding, thrombosis or an auto-immune disorder.

PMID- 11579870
TI  - Rational use of drugs against Plasmodium falciparum.
AB  - Recent studies on resistance to blood schizontocides in Plasmodium falciparum
      give a rational basis for the use of artemisinins combined with arylaminoalcohols
      for the treatment of uncomplicated chloroquine-resistant malaria in Africa. In
      areas where such combinations are introduced, there is reason to believe that the
      continued use of chloroquine in the community will help protect the new drugs
      from resistance. In view of several laboratory studies, combinations of
      artemisinins with antifolates or chloroquine pose a risk of antagonistic
      interaction. This can be avoided by use of the artemisinin and the companion drug
      sequentially.

PMID- 11579871
TI  - How can we do pharmacokinetic studies in the tropics?
AB  - Information regarding the pharmacokinetic (PK) and pharmacodynamic (PD)
      properties of a drug provides the basis for optimizing dosing. PK-PD information
      should be obtained from patients representative of the overall target population,
      but in many tropical hospitals or health care facilities it may be medically
      hazardous or logistically difficult for an ill patient or a young child to be
      sampled repeatedly. Traditional methods used to determine the pharmacokinetic
      properties of a drug require analysis of a large number of blood samples per
      subject. However, using modern statistical methods, sparse datasets (i.e. with
      assay results from only a few, or as little as one blood sample per subject) can
      now be analysed by a method termed 'the population approach'. Modern assay
      techniques can often be adapted to small blood volumes allowing finger prick
      blood samples to be taken. One of the major aims of the population approach is to
      distinguish and characterize patient and disease contributors to inter-individual
      variance in drug pharmacokinetics. The purpose of this paper is to explain the
      basis of the population approach, to highlight its advantages compared to
      traditional methods of analysis, and to review the application of the population
      approach to data from field studies of antimalarial drugs. The design of
      population pharmacokinetic studies is also discussed briefly. The principles
      discussed in the paper are also applicable to pharmacodynamic data.

PMID- 11579872
TI  - Insecticide-treated materials, mosquito adaptation and mass effect: entomological
      observations after five years of vector control in Burkina Faso.
AB  - Insecticide-treated bednets and curtains have been shown to be successful in
      reducing malaria transmission and child mortality in Africa over periods of up to
      2 years. A major concern relating to this approach is that, in time, it will be
      compromised by the selection of mosquito genotypes that are resistant at the
      biochemical or behavioural level. We report entomological data from a large area
      in Burkina Faso where insecticide-treated curtains have been in use for up to 5
      years. Longitudinal indoor and outdoor CDC light-trap catches were performed in 4
      sentinel villages. In addition cross-sectional surveys using indoor spray catches
      and outdoor CDC light-trap catches were performed each September in a larger
      number of villages, including 8 located outside the intervention area. We found
      no evidence of the selection of mosquito phenotypes that might compromise the
      intervention. Indoor and outdoor vector densities remained very low after 5 years
      of intervention, both compared with pre-intervention levels and with concurrent
      levels outside the intervention area. We found no evidence of a switch to outdoor
      rather than indoor biting. The proportion of blood meals taken on humans may have
      decreased but our data are inconclusive on this point. We observed higher vector
      densities and sporozoite rates at the periphery of the intervention zone than at
      the centre, which may reflect re-invasion of peripheral villages by mosquitoes
      from outside the intervention area. In 'real life' programmes, with perhaps
      patchy, less than optimal coverage, the protection against malaria transmission
      provided to individuals using insecticide-treated materials may be less than that
      achieved in the randomized controlled trials which demonstrated an impact of
      insecticide-treated materials on child mortality.

PMID- 11579873
TI  - Microbial keratitis in Hong Kong: relationship to climate, environment and
      contact-lens disinfection.
AB  - Microbial keratitis has been studied in Hong Kong as a representative sub
      tropical climate of south China. An 18-month investigation in 1997/98 of 223
      cases of ulcerative keratitis (presumed microbial) was conducted in the 2 million
      population of Shatin and Kowloon at the Prince of Wales and Hong Kong Eye
      Hospitals respectively with comprehensive microbiology. A case-control study was
      pursued at the same time between 45 contact-lens wearers (CLW) developing
      microbial keratitis and 135 lens-wearing volunteers matched for age, sex,
      educational status and visual acuity. Home water supplies were sampled for
      Acanthamoeba. Previous ocular surface disease and trauma (preventable by wearing
      goggles for grinding) were common predisposing causes while cosmetic wear of
      contact lenses was responsible for 26% of cases overall. Pseudomonas aeruginosa
      was the commonest bacterium isolated, from both CLW and non-CLW, with infection
      being acquired within the community. These 28 pseudomonads remained fully
      sensitive to the third-generation cephalosporins, aminoglycosides and quinolone
      antibiotics, which is very encouraging. Fungi were isolated, predominantly
      Fusarium sp., but less commonly than expected. A fungal/bacterial ratio was
      obtained of 1/17, while in comparison, the expected ratio for a tropical climate
      ranges from 1/5 (Singapore) to 1/2 (South India). Acanthamoeba was the second
      commonest microbe isolated from keratitis of CLW. The domestic water environment
      of 8% of homes of both patients and controls wearing contact lenses was colonized
      with Acanthamoeba. Lack of hygiene, use of tap water for storing lenses, failure
      to air-dry lens-storage cases or use of one-step hydrogen peroxide disinfectant
      were identified as risk factors for keratitis in CLW. The study results commend
      use of multipurpose solutions by CLW in Hong Kong to achieve the lowest expected
      rates of infection.

PMID- 11579874
TI  - The economic imperative of Nipah virus surveillance in Indonesia.

PMID- 11579875
TI  - The risk of yellow fever in a dengue-infested area.
AB  - Yellow fever and dengue are viral infections that in urban centres are
      transmitted by the same arthropod vector, a mosquito of the genus Aedes. In order
      to estimate the risk of an epidemic of urban yellow fever in a dengue-infested
      area we calculated the threshold in the basic reproduction number, R0, of dengue,
      above which any single sylvatic yellow fever-infected individual will trigger an
      urban yellow fever epidemic. Specifically, we analysed the relationship between
      the extrinsic incubation period and the duration of viraemia, from which it is
      possible to define the R0 for dengue that would also suggest an outbreak
      potential for yellow fever. We also calculated the critical proportion of people
      to vaccinate against yellow fever in order to prevent an epidemic in a dengue
      endemic area. The theory proposed is illustrated by the case of Sao Paulo State
      in southern Brazil, where dengue is endemic and the risk of urban yellow fever is
      already imminent.

PMID- 11579876
TI  - A first case of cutaneous leishmaniasis due to Leishmania (Viannia) lainsoni in
      Bolivia.
AB  - We present the first known case of cutaneous leishmaniasis due to Leishmania
      (Viannia) lainsoni detected in Bolivia. The parasite was isolated from a young
      girl living in the subtropical region of Carrasco (900-1000 m above sea level,
      Caranavi Province, Department of La Paz, Bolivia). The parasite identification
      was confirmed by multilocus enzyme electrophoresis.

PMID- 11579877
TI  - Blastocystis hominis in high-rise flat dwellers in Kuala Lumpur, Malaysia.

PMID- 11579878
TI  - Prevalence, intensity, and fertility of ovine cystic echinococcosis in the
      central Peruvian Andes.
AB  - An abattoir survey of 212 sheep of different ages was undertaken to determine the
      local epidemiological transmission patterns of Echinococcus granulosus in the
      central Peruvian Andes. Overall prevalence of the disease in sheep in this survey
      (which ended in July 1996) was 77.4%, with 96% of sheep aged > or = 6 years being
      infected. Of 1165 cysts examined, 41.1% were fertile with a mean protoscolex
      viability of 73.2%. A logistic regression model for the distribution of cyst
      fertility and type by age, location and size is described. Mathematical modelling
      also determined that infection pressure on sheep was 0.44 infections per year and
      that the mean number of cysts increased linearly by 1.28 cysts per year. These
      data suggest that E. granulosus is in an endemic state in this area and control
      measures could drive the disease towards extinction.

PMID- 11579879
TI  - A population-based prevalence survey of skin diseases in adolescents and adults
      in rural Sumatra, Indonesia, 1999.
AB  - Skin disorders are one of the most common presenting health problems and pose a
      considerable public health problem in developing and developed countries. A
      population-based survey (n = 917) was conducted in October and November 1999 to
      determine the prevalence of skin diseases in 3 rural villages in Indonesia (Riau
      province, Sumatra). The overall individual response rate was 96%. Household
      interviews were conducted to obtain information on skin conditions, basic socio
      demographic factors and lifestyle habits. Trained doctors performed a thorough
      clinical skin examination of each subject in the household. The overall
      prevalence of skin disease in the 3 villages was 28.2% (95% confidence intervals
      24.6-31.8). The prevalence of fungal infections (12.0%) was twice as high as
      dermatitis (5.1%). As skin conditions are common in rural Indonesia, it is
      advisable to improve the training of nurses and doctors in the prevention and
      treatment of skin disorders.

PMID- 11579880
TI  - Taenia solium infection in Irian Jaya (west Papua), Indonesia: a pilot
      serological survey of human and porcine cysticercosis in Jayawijaya district.

PMID- 11579881
TI  - The detection of Plasmodium falciparum and P. vivax in DNA-extracted blood
      samples using polymerase chain reaction.
AB  - Seventeen pairs of published primer sets were compared for their relative
      sensitivity to detect malaria DNA extracted from blood samples, which were
      obtained from Pakistani patients suffering from malaria. The primer sets
      investigated consisted of: (i) 9 pairs of direct primers and 3 sets of nested
      primers for detecting Plasmodium falciparum, (ii) 2 pairs of direct primers and 2
      sets of nested primers for detecting P. vivax, and (iii) 1 set of multiplex
      primers for detecting both P. falciparum and P. vivax, simultaneously. After a
      miniscreen of 9 DNA-extracted blood samples using the 17 primer sets stated
      above, 5 primer sets were short-listed (based on their superior sensitivity) and
      used for a maxi-screen of DNA extracted from 126 microscopy-positive blood
      samples from Pakistan, with the following results. (i) For the detection of P.
      falciparum, the direct primer pair 'PF1 + PF2' gave a sensitivity of 95% and the
      nested primer set 'RIT405 + RIT406/RIT371 + RIT372' gave a sensitivity of 97%.
      (ii) For the detection of P. vivax, the direct primer pair 'Forward + Reverse'
      and the nested primer set 'PLF + UNR/PLF + VIR' both gave a sensitivity of 94%.
      (iii) The nested multiplex primer set 'rPLU5 + rPLU6/rFAL1 + rFAL2 + rVIV1 +
      rVIV2' gave a sensitivity of 97% and 96% for P. falciparum and P. vivax,
      respectively. It was concluded that the nested multiplex primer set was the most
      optimal primer set to use for the detection of malaria DNA extracted from blood
      samples. Furthermore, the nested multiplex primer set has the advantage of
      simultaneously detecting and differentiating between P. vivax and P. falciparum.

PMID- 11579882
TI  - A comparison of a string test-PCR assay and a stool antigen immunoassay (HpSA)
      for Helicobacter pylori screening in Peru.

PMID- 11579883
TI  - A fast agglutination screening test (FAST) for the detection of anti-Leishmania
      antibodies.

PMID- 11579884
TI  - Pneumocystis carinii pneumonia in patients being registered for smear-negative
      pulmonary tuberculosis in Malawi.
AB  - The National TB Control Programme of Malawi registers and treats large numbers of
      patients with chronic cough for smear-negative pulmonary tuberculosis (PTB).
      Smear-negative PTB is diagnosed according to clinical and radiographic criteria,
      as mycobacterial cultures are not routinely available. In an area of high HIV
      seroprevalence there is a concern that other opportunistic infections apart from
      TB, such as Pneumocystis carinii, may be missed owing to lack of diagnostic
      facilities. The aims of this study were to investigate (i) the extent of P.
      carinii pneumonia (PCP) in patients about to be registered for smear-negative
      PTB; (ii) whether there were any clinical or radiological features that could
      help identify PCP in the absence of more detailed investigations; and (iii) the
      treatment outcome of PCP patients. A cohort of 352 patients who were about to be
      started on treatment for smear-negative PTB were investigated further in 1997-99
      by clinical assessment, HIV testing and bronchoscopy. HIV sero-prevalence was 89%
      (278/313). A total of 186 patients underwent bronchoscopy and bronchoalveolar
      lavage, and PCP was diagnosed by indirect immunofluorescence or polymerase chain
      reaction in 17 (9%) of this subgroup. Dyspnoea was significantly more common in
      PCP cases compared to non-PCP cases (RR 1.35; 95% CI 1.24-1.48; P = 0.008), but
      discrimination between the groups was difficult using clinical criteria alone.
      The outcome of PCP cases was poor despite management with high-dose co
      trimoxazole and secondary co-trimoxazole prophylaxis, with a median survival of 4
      months (25-75% range: 2-12 months).

PMID- 11579885
TI  - A long-term follow-up of asymptomatic amicrofilaraemic individuals living in a
      filaria-endemic region of Orissa, India: infection and disease status.
AB  - A group of asymptomatic amicrofilaraemic individuals (endemic normals) aged > 12
      years was identified in 2 filaria-endemic villages of Orissa, India in 1990
      (Bajapur village, n = 40) and in 1994 (Olosingh village, n = 47). They were re
      examined for microfilaraemia and disease status in the year 2000 after a 10-year
      and a 6-year period. Studies conducted at both villages yielded a similar pattern
      in the development of disease. Above 85% of the females remained normal, compared
      to 54% of males. Remaining individuals had acquired hydrocoele (males) and
      adenolymphangitis (both males and females). Only 1 individual converted to having
      asymptomatic microfilariae. No case of elephantiasis was observed. Results
      indicate that most females remained normal and males faced considerable risk of
      developing hydrocoele in these Wuchereria bancrofti-endemic areas.

PMID- 11579886
TI  - Acute lower respiratory infections among children hospitalized in Bangui, Central
      African Republic: toward a new case-management algorithm.
AB  - To measure the performance of the current WHO algorithm in identifying children
      at higher risk of death, children aged 2-59 months who presented with cough
      and/or difficult breathing and were admitted into the paediatric hospital of
      Bangui (Central African Republic) during a 1-year period (1996/97) were
      investigated. Among children with subcostal indrawing, mortality and severity of
      oxygen desaturation were identical whether or not they also had tachypnoea. Among
      children with a 'severe pneumonia', those who also fulfilled the 'very severe
      disease' definition had a higher risk of death (31/132, 23.5%) than those who did
      not (12/106, 11.3%, P = 0.02). However, this 'very severe disease' definition did
      not predict death when used in children who did not have severe pneumonia. To
      identify variables that would better predict death, combinations of symptoms and
      signs were examined among the subgroup of children with indrawing. Nine
      combinations had both a sensitivity and specificity over 60%. 'Grunting and/or
      nasal flaring' had a sensitivity of 72% and a specificity of 66% in predicting
      death, and might be easier to use by primary health care personnel than other
      combinations. A new algorithm is proposed for the management of children aged 2
      59 months presenting with cough and/or difficult breathing. The definition of
      pneumonia would be unchanged (tachypnoea). Severe pneumonia would remain defined
      on indrawing regardless of respiratory rate, except that indrawing should be
      lower chest wall and/or intercostal. In health facilities where intravenous
      antibiotics, chloramphenicol and/or oxygen are available, entry into a 'very
      severe pneumonia' category would be based on 'grunting and/or nasal flaring'
      among children with indrawing. In our study population, the mortality rates in
      the categories based on these definitions were 0.8% (1/127) in children with no
      pneumonia, 0.9% (1/116) in children with pneumonia, 7.7% (12/156) in children
      with severe pneumonia and 31.1% (33/106) in children with very severe pneumonia.

PMID- 11579887
TI  - Malaria in southern Thailand: relationship between parasitaemia and disease.

PMID- 11579888
TI  - High mortality from snakebite in south-eastern Senegal.
AB  - Over 24 years, from 1976 to 1999, we conducted a prospective study of overall and
      cause-specific mortality among the population of 42 villages of south-eastern
      Senegal. Of 4228 deaths registered during this period, 26 were caused by
      snakebite, 4 by invertebrate stings and 8 by other wild or domestic animals. The
      average annual mortality rate from snakebite was 14 deaths per 100,000
      population. Among persons aged > or = 1 year, 0.9% (26/2880) of deaths were
      caused by snakebite and this cause represented 28% (26/94) of total deaths by
      accidents. We also investigated the snake fauna of the area. Of 1280 snakes
      belonging to 34 species that were collected, one-third were dangerous and the
      proportion of Viperidae, Elapidae and Atractaspidae was 23%, 11% and 0.6%,
      respectively. The saw-scaled viper Echis ocellatus was the most abundant species
      (13.6%). Other venomous species were Causus maculatus (6.5%), Naja katiensis
      (5.5%), Bitis arietans (2.7%), Elapsoidea trapei (2.4%), Naja nigricollis (1.2%),
      Naja melanoleuca (1.1%), Atractaspis aterrima (0.4%), Dendroaspis polylepis
      (0.3%) and Naja haje (0.1%).

PMID- 11579889
TI  - The safety of the combination artesunate and pyrimethamine-sulfadoxine given
      during pregnancy.
AB  - Malaria during pregnancy is associated with an increased risk of severe anaemia
      and low-birthweight babies. Effective intermittent therapy with pyrimethamine
      sulfadoxine (PSD) decreases parasitaemia and severe anaemia and improves
      birthweight in areas where Plasmodium falciparum is sensitive to this drug.
      Increasing resistance to PSD is a concern and alternative antimalarial regimens
      during pregnancy are needed. Artesunate with PSD is a promising antimalarial
      combination but few data are available on the safety of artemisinins when taken
      during pregnancy. Outcome of pregnancy was evaluated for 287 women in The Gambia
      who were exposed in June 1999 to a single dose of the combination artesunate and
      PSD during a mass drug administration and 172 women who were not exposed. Women
      who received placebo (40) and those who did not participate in the mass drug
      administration (132) comprised the non-exposed group. There was no difference in
      the proportion of abortions, stillbirths, or infant deaths among those exposed or
      not exposed to the drugs. The mean weight of 18 infants born to mothers who had
      received artesunate and PSD during the third trimester was 3.10 kg compared to a
      mean weight of 2.62 kg of the 10 infants of untreated mothers (adjusted P value =
      0.05). We found no evidence of a teratogenic or otherwise harmful effect of
      gestational exposure to artesunate and PSD. Treatment of a self-selected group of
      pregnant women with PSD and artesunate during pregnancy was associated with a
      greater birthweight, which may have resulted from clearance of malaria parasites.
      However, the influence of confounding factors cannot be excluded.

PMID- 11579890
TI  - Causal prophylactic efficacy of atovaquone-proguanil (Malarone) in a human
      challenge model.
AB  - Plasmodia infect the liver for about 7 days before subsequently infecting the
      blood. Present prophylaxis against Plasmodium falciparum malaria employs agents
      that primarily kill blood stages and must be continued for 28 days after the last
      exposure. Atovaquone-proguanil (Malarone) is a new antimalarial agent that is
      licensed in 35 countries as treatment against blood-stage infection, but its
      components (atovaquone and proguanil) have separately been shown to be active
      also against liver stages. To determine whether atovaquone-proguanil is
      sufficiently active against liver stages to be discontinued 7 days after
      exposure, we challenged 16 volunteers with P. falciparum via infected mosquitoes.
      Twelve volunteers received atovaquone-proguanil (1 tablet daily) on the day prior
      to challenge, on the day of challenge, and for the next 6 days; 4 volunteers
      received matching placebo. All placebo volunteers demonstrated parasitaemia and
      malarial symptoms beginning on days 11-12 after challenge. No atovaquone
      proguanil volunteer acquired malaria. Atovaquone-proguanil is the first licensed
      antimalarial agent that kills P. falciparum in the liver and that may be
      discontinued 7 days after the last exposure.

PMID- 11579891
TI  - A trial of proguanil-dapsone in comparison with sulfadoxine-pyrimethamine for the
      clearance of Plasmodium falciparum infections in Tanzania.
AB  - Considerable levels of resistance to sulfadoxine-pyrimethamine (SP) have been
      reported in Plasmodium falciparum in north-eastern Tanzania, and the
      identification of a suitable antimalarial to replace SP is now a high priority.
      We conducted a trial in July 2000 to determine the efficacy of proguanil (PG)
      plus dapsone (DS), compared with that of SP, for the treatment of asymptomatic
      falciparum infection. A total of 220 children with parasitaemia > or = 2000 per
      microL completed the study; 112 had received a single dose of SP (dosage
      calculated for pyrimethamine 1.25 mg/kg and sulfadoxine 25 mg/kg) and 108 had
      taken PG 10 mg/kg with DS 2.5 mg/kg each day for 3 days. Clearance of asexual
      parasites at day 7 was 14.3% with SP, but 93.5% with PG-DS. The remarkably high
      failure rate with SP was not associated with occurrence of leucine substitution
      at position 164 of the dhfr gene. Both treatment regimens were well tolerated.
      Compared with available data on another antifolate combination, chlorproguanil
      dapsone ('Lapdap'), PG-DS was slightly but significantly inferior in achieving
      parasite clearance (99.5% versus 93.5%). The estimated cost of a 3-day course of
      PG-DS treatment for a child weighing 18 kg is US $0.15. With the rising incidence
      of SP-resistant P. falciparum infection, PG-DS could provide an effective,
      affordable and already available therapeutic alternative for malaria in East
      Africa at least until chlorproguanil-dapsone is registered.

PMID- 11579892
TI  - Chloroquine-resistant Plasmodium falciparum malaria among children seen in a
      regional hospital, Tabuk, Saudi Arabia.

PMID- 11579893
TI  - Human susceptibility to Schistosoma japonicum in China correlates with antibody
      isotypes to native antigens.
AB  - Antibody isotypic responses (IgE, IgA, IgG1, IgG2, IgG3 and IgG4) to Schistosoma
      japonicum antigens--adult worm (AWA), soluble egg (SEA) and the recombinant
      proteins TEG (22.6-kDa tegumental antigen, Sj22) and PMY (paramyosin, Sj97)--were
      measured (in 1998) in a cohort of 179 Chinese subjects 2 years post-treatment.
      Subjects in the highest intensity re-infection group (> 100 eggs per gram faeces)
      had significantly higher levels of IgG1 and IgG4 against AWA. Analysis of
      IgG4/IgE ratios for AWA and SEA linked IgG4 excess to re-infection and IgE excess
      to non-re-infection. Two years after chemotherapeutic cure, 29 subjects, who were
      re-infected or never infected but highly water-exposed, were classified as
      epidemiologically susceptible (n = 15) or epidemiologically insusceptible to
      infection (n = 14). IgG4 levels against native antigens (AWA and SEA) were higher
      in susceptible and IgE levels were higher in insusceptible but antibody responses
      to the recombinant proteins (PMY and TEG) showed no clear pattern or difference
      between susceptibility groups. These and earlier findings provide evidence that
      immunity develops against schistosomiasis japonica in China and that
      susceptibility/resistance correlates with antibody isotypes against native
      schistosome antigens.

PMID- 11579894
TI  - Lack of induction of interleukin-2-receptor-alpha in patients with tuberculosis
      and human immunodeficiency virus co-infection: implications for pathogenesis.
AB  - Since expression of both interleukin-2 (IL-2) and IL-2-receptor-alpha (IL-2R
      alpha) by lymphocytes is inhibited by human immunodeficiency virus (HIV) in
      vitro, we hypothesized that HIV-co-infection among persons with tuberculosis (TB)
      might impair T-lymphocyte responses to TB via this mechanism. We measured soluble
      IL-2R-alpha (sIL-2R-alpha), a surrogate marker of T-lymphocyte activation and
      proliferation, and soluble tumour necrosis factor receptor I (sTNF-RI) in sera
      from West African patients categorized into 4 groups: those with TB alone (TB+
      HIV-, n = 55), CD4-matched groups with TB and HIV co-infection (TB+ HIV+, n = 50)
      or HIV infection alone (TB- HIV+, n = 35), and patients with neither disease (TB-
      HIV-, n = 35). The median level of sIL-2R-alpha was markedly greater in the TB+
      HIV- group (1580 U/mL) compared to the TB- HIV- (670 U/mL; P < 0.001) and TB-
      HIV+ (880 U/mL; P < 0.01) groups. More importantly, the median concentration of
      sIL-2R-alpha was much lower in the TB+ HIV+ group (855 U/mL) compared to the TB+
      HIV- group (1580 U/mL; P < 0.01) despite similar levels of sTNF-RI. These results
      suggest that T-lymphocyte activation in TB patients is impaired by HIV co
      infection and, furthermore, this suppressive effect was independent of numerical
      depletion of CD4 lymphocytes. Impairment to IL-2-signalling might contribute to
      the profound impact that HIV has had on both the incidence and the
      clinicopathological manifestations of TB.

PMID- 11579895
TI  - The role of nutritional status and insulin-like growth factor in reduced physical
      growth in hepatosplenic Schistosoma mansoni infection.
AB  - The influence of nutritional status and hormonal growth activity on the impaired
      somatic development of adolescents with the hepatosplenic clinical form of
      Schistosoma mansoni infection (HS), the intestinal form with high (IH) or low
      (IL) egg output and non-infected (NI) individuals was evaluated (in Comercinho,
      Minas Gerais State, Brazil, in 1996-97) by measuring body mass index (BMI),
      insulin-like growth promoting factor (IGF-I) and its carrier protein (IGFBP-3).
      BMI, IGF-I and IGFBP-3 concentrations were significantly lower in the HS group
      compared with the IH and the NI groups, irrespective of age. BMI did not remain
      associated with the clinical form in the bi-variate model that included IGF-I and
      BMI or IGFBP-3 and BMI, suggesting that in these groups IGF-I and IGFBP-3 levels
      were related to the clinical form but independent of nutritional status. It is
      suggested that physical growth impairment in hepatosplenic S. mansoni infection
      results from the synergistic action of both hepatic damage and nutritional
      restriction.

PMID- 11579896
TI  - General concepts of consultation-liaison psychiatry in Japan.

PMID- 11579897
TI  - Drug-induced psychosis in Japan.

PMID- 11579898
TI  - Diabetes mellitus as so-called psychosomatic disease in Japan.

PMID- 11579899
TI  - Psychooncology in Japan.

PMID- 11579900
TI  - Psychonephrology in Japan.

PMID- 11579901
TI  - Transplant psychiatry in Japan.

PMID- 11579902
TI  - Psychiatric problems of patients with HIV/AIDS in Japan.

PMID- 11579903
TI  - Necrotizing fasciitis: a case of clostridial myonecrosis.

PMID- 11579904
TI  - [Ct-assisted navigation for insertion of dental implants in maxilla models].
AB  - The use of CT-based intraoperative navigation has greatly improved controlled
      surgery in many specialties. In this study the precision of the SMN system
      (Zeiss, Oberkochen, Germany) for navigated drilling and following implantation in
      the maxilla is evaluated. This study should prove the suitability of navigation
      systems for computer-assisted implantation in the maxilla to avoid perforation to
      the maxillary sinus. Therefore 60 target drills were carried out on 10
      standardized polyurethane milling models after CT-scanning. The models were
      produced with cranial open maxillary sinuses. The CT-scans were performed with a
      slice distance of 1 mm. Then the CT-data were transferred to the workstation of
      the SMN system (Zeiss, Oberkochen, Germany) and a referenciation of the fiducials
      for superposition of the native and CT model were done. Referenciation of the
      model was performed with the aid of a drilling tool. This drilling tool was used
      for later navigation-assisted drilling into the upper jaw. The target of drilling
      was the maxillary sinus floor. The aim was to come as near as possible without
      perforation. The distance of the bottom of the drilling holes to the maxillary
      sinus floor were measured after section of the model. An average drilling depth
      of 6.97 mm (s=0.4) and a mean distance to sinus floor of 0.11 mm (s=0.2) was
      found. In 13 cases the lower board of sinus was perforated.In conclusion a high
      precision of CT-based navigation for controlled preimplantological drilling was
      seen.

PMID- 11579905
TI  - [Engine-driven preparation of curved root canals: a platform to assess physical
      parameters].
AB  - The number of engine-driven rotary instruments available on the market is
      steadily increasing. These instruments enable clinicians to prepare better shaped
      root canals, however, rotary instruments have a higher risk for fracture than
      hand instruments. Unfortunately, the stresses placed on engine-driven rotary
      instruments in curved canals are insufficiently studied. The aim of this study
      was to develop a device which could measure more accurately the physical
      parameters influencing rotary instruments in curved canals. For this purpose, a
      specially designed machine was constructed to measure the torque which develops
      between the rotary instrument and the motor. Apical forces and penetration depths
      could also be directly measured in real time. A variety of other measurements was
      also possible because of other special set-ups integrated into the device. In the
      current study torque was assessed for GT-Files, size 35 with a .12 and sizes 20
      with a .12 to .06 taper. In additions to preparations in simulated canals in
      plastic blocks, the "ISO 3630-1 specification for fracture moment" and "number of
      cycles till fatigue fracture" was measured. The findings indicated that when
      instruments were used for preparations, torques up to 40 Nmm were present. This
      exceeded the static fracture load, which was less than than 13 Nmm for the size
      20 with .12 taper. In contrast, the number of rotations were more than 10 times
      lower when shaping canals in plastic blocks with a 5 mm radius of curvature than
      the number of rotations to fracture in the "cyclic fatigue test". This suggests
      that a GT-instrument could be used in ten canals. The apical force was always
      greater than 1 N and occasionally, 8 N or more was recorded. Further studies on
      natural teeth with varying canal geometries are required using the specially
      developed torsional machine to reduce the incidence of instrument fracture. In
      this way an efficient clinical potential can be confirmed for engine-driven
      rotary instruments in canal preparation.

PMID- 11579906
TI  - Mediastinal cystic teratoma associated with a Hodgkin's lymphoma.

PMID- 11579907
TI  - Mediastinoscopy as a standardised procedure for mediastinal lymph-node staging in
      non-small cell carcinoma. Do we have to accept the compromise?

PMID- 11579908
TI  - Complete myocardial revascularisation without cardiopulmonary bypass.

PMID- 11579909
TI  - Post operative assessment of a bioprosthetic aortic valve (Labcor).

PMID- 11579910
TI  - ACOG (American College of Obstetricians and Gynecologists) committee opinion.
      Genetic screening for hemoglobinopathies, number 238, July 2000 (replaces number
      168, February 1996). Committee on Genetics.

PMID- 11579911
TI  - ACOG (American College of Obstetricians and Gynecologists) educational bulletin.
      Adult manifestation of childhood sexual abuse, number 259, July 2000. Clinical
      management guidelines for obstetrician-gynecologists.

PMID- 11579912
TI  - First scientific workshop on Hallervorden-Spatz syndrome: executive summary.

PMID- 11579913
TI  - Pigmentary dispersion syndrome.

PMID- 11579914
TI  - Experience with indocyanine green dye.

PMID- 11579915
TI  - Expanding the role of bioptics to the pseudophakic patient.

PMID- 11579916
TI  - Anterior capsular flap incarceration into the clear corneal side port.

PMID- 11579917
TI  - Consultation section. Refractive surgical problem.

PMID- 11579918
TI  - A research program for the osteopathic profession. 1948.

PMID- 11579919
TI  - Research our great and only hope.

PMID- 11579920
TI  - Hoehler's adjusted kappa is equivalent to Yule's Y.

PMID- 11579921
TI  - Hybrid reactor performance in pentachlorophenol (pcp) removal by anaerobic
      granules.
AB  - The present research aimed at evaluating pentachlorophenol (PCP) degradation in a
      hybrid reactor supplied with a mixture of fatty acids (propionic, butyric, acetic
      and lactic) and methanol. The performance of the reactor is remarkably stable and
      efficient during PCP additions at range of 2.0 to 21.0 mg/L. The reduction of
      chemical oxygen demand (COD) was around 97% and methane was found to be 88% in
      the biogas production. The efficiency of volatile fatty acids breakdown was 93%,
      64% and 74% respectively for butyric, propionic and acetic. PCP total removal of
      more than 99% was reached by granular sludge activities formed during 21 months
      of reactor operation. Methanogenic microorganisms predominance was noticed with
      10(5) to 10(6) cells/mL during enumeration on methanol or lactate added to
      sulfate culture media. The removal rate was 1.07 mg PCP.g-1 VS.d-1 during the
      highest PCP concentration addition.

PMID- 11579922
TI  - Post-treatment of anaerobic effluents in an overland flow system.
AB  - This research aimed at the investigation of an overland flow system applied to
      the post-treatment of anaerobic effluents. The system treated domestic sewage in
      Itabira City (Brazil), being composed by an anaerobic reactor and an overland
      flow system, the latter working as a post-treatment unit. A portion of the
      reactor's effluent was directed to a group of three overland flow slopes
      (demonstration scale), that were operated with different application rates.
      During Phase 1 of the research the overland flow system was fed under a permanent
      hydraulic regime (constant flows), having as inflow the effluent from an UASB
      reactor (full-scale, volume of 477 m3). During Phase 2, the overland system was
      fed under a hydraulic transient pattern (variable flows with hourly variations),
      having as inflow the effluent from a partitioned UASB reactor (demonstration
      scale, volume of 9 m3). In general, the performance of the overland flow system
      as a polishing step was very good, mainly because of the low solids and organic
      matter concentration in the final effluent (average values of BOD from 48 to 62
      mg/L; COD from 98 to 119 mg/L and SS from 17 to 57 mg/L). Regarding nutrients and
      coliforms, the system also reached satisfactory efficiency levels. Based on the
      experience obtained with this study, it is suggested that overland flow systems,
      working as post-treatment step of UASB reactors, can work with application rates
      in the range of 0.4 to 0.5 m3/m.h, which are higher than those normally applied.

PMID- 11579923
TI  - Psychrophilic one- and two-step systems for pre-treatment of winery waste water.
AB  - The operation performance of a single and two (in series) laboratory UASB
      reactors (working volume of 2.7 l, recycle ratio varied from 1:1 to 1:18)
      treating diluted wine vinasse was investigated under psychrophilic conditions (4
      10 degrees C). For a single UASB reactor seeded with granular sludge, the average
      organic loading rates (OLR) applied were 4.7, 3.7 and 1.7 g COD/l/d (hydraulic
      retention times (HRTs) were around 1 d) at 9-11, 6-7 and 4-5 degrees C,
      respectively. The average total COD removal for preacidified vinasse wastewater
      was around 60% for all the temperature regimes tested. For two UASB reactors in
      series, the average total COD removal for treatment of non-preacidified
      wastewater exceeded 70% (the average OLRs for a whole system were 2.2, 1.8 and
      1.3 g COD/l/d under HRTs of 2 days at 10, 7 and 4 degrees C, respectively). In
      situ determinations of kinetic sludge characteristics (Vm and Km) revealed the
      existence of substantial mass-transfer limitations for the soluble substrates
      inside the reactor sludge bed. Therefore an application of higher recycle rations
      is essential for enhancement of UASB pre-treatment under psychrophilic
      conditions. The produced anaerobic effluents were shown to be efficiently post
      treated aerobically--final effluent COD concentrations were around 0.1 g/l.

PMID- 11579924
TI  - Domestic sewage treatment in full-scale UASBB plant at Mangueira, Recife,
      Pernambuco.
AB  - The anaerobic technology application for domestic sewage treatment in Pernambuco
      State (Brazil) is relatively recent. Some UASB reactors of less than 250 m3 were
      built in the Recife Metropolitan Region (RMR) in the 1990s. Mangueira (18,000
      inhabitants) was the first neighborhood where the municipality built a plant with
      a bigger UASB reactor of 810 m3. It was intended to evaluate the performance and
      verify if such technology would be feasible. The objective would be the possible
      application of UASB reactors to the RMR, according to the new sewage master-plan
      under elaboration that would benefit about 3 million inhabitants. The monitoring
      of the Mangueira UASB reactor over 30 months showed that satisfactory results
      were obtained. Three distinct operational phases occurred, in which efficiency
      varied from 60% up to 90% based on COD removal. The results were very dependent
      on the operation and maintenance, either in the plant or in the sewage
      collection. Significant amount of inert solids was measured inside the reactor.
      Despite the operational problems, the UASB was shown to be very robust and
      stable. Under high fluctuation of influent concentrations (150-750 mg COD/L)
      during the period, resulting in applied organic loading rate of 0.5 to 2.5 kg
      COD/m3.d, the average values of COD removal efficiency did not change
      significantly. An active biomass with specific methanogenic activity varying from
      0.18 to 0.25 g COD/g VSS.d was measured at the end of the period.

PMID- 11579925
TI  - A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare
      hyperfractionation and two variants of accelerated fractionation to standard
      fractionation radiotherapy for head-and-neck squamous cell carcinomas: first
      report of RTOG 9003: in regard to Fu et al. IJROBP 2000;48:7-16. Actuarial
      estimates of late normal-tissue effects...now!

PMID- 11579926
TI  - Perinatal and lifetime exposure to methylmercury in the mouse: blood and brain
      concentrations of mercury to 26 months of age.
AB  - Chronic, low-level exposures to environmental toxicants, because they often begin
      prenatally and then persist throughout the individual's lifetime, pose
      challenging issues to risk assessment. Exposure to low levels of methylmercury
      through the diet, based largely on consumption of fish and sea mammals, follows
      this pattern. Early development is considered to be a period of heightened
      vulnerability during which even low-level exposures may produce undetected,
      "silent", damage that is revealed only under conditions that challenge the
      functional capacities of the individual. Aging, with its diminished functional
      capacities and compensatory reserves provides such a challenge, but, to explore
      this possibility, requires basic information about blood and brain levels under
      conditions of chronic lifetime exposure. The current research was undertaken to
      provide such information. One hundred female B6C3F1/HSD mice were assigned to one
      of three dose groups, 0, 1, or 3 ppm methylmercury chloride administered in a 5
      nM sodium carbonate drinking solution. They were bred with male CBA/J HSD mice to
      produce the trihybrid offspring B6C3F1/ HSD x CBA/J HSD. Dosing of the females
      began 4 weeks prior to breeding and continued for the two methylmercury-exposed
      groups throughout breeding and gestation. The methylmercury-treated litters were
      split into two subgroups, one exposed throughout its lifetime (set at 26 months)
      to the original dose, the other exposed through postnatal day 13 (PND 13). Brain
      and blood concentrations were assayed by cold-vapor atomic absorption. Samples
      were obtained on PND 4 and 21, and then at the end of months 14 and 26. On PND 4,
      brain and blood levels closely reflected maternal dosing. In all groups,
      concentrations fell sharply from PND 4 to 21, but to a greater extent in the
      perinatal groups. Blood levels in the 1 ppm lifetime group remained unchanged
      between months 14 and 26, but brain levels rose modestly. In the 3 ppm lifetime
      group, both brain and blood levels rose significantly between months 14 and 26,
      suggesting an interaction between dose and age.

PMID- 11579927
TI  - Adjustment of prognostic effects in prevalent case-control studies on genotype.
AB  - Since genotypes are unchangeable, adjustment of prognostic effects in prevalent
      case-control studies may produce an unbiased estimate of odds ratio (OR) for
      disease occurrence. In this paper, the prognostic effects on OR is demonstrated,
      then three approaches to examine and/or adjust the OR are presented. The
      demonstration shows that the prognostic effects are larger in diseases with poor
      prognosis than in those with better prognosis. Genotypes increasing disease risk
      and fatality rate are underestimated, while those increasing the risk and
      improving prognosis are overestimated. The simplest approach to examine the OR
      derived from prevalent case-control studies is to conduct stratified analysis
      according to the interval between diagnosis and study enrollment. When the
      stratified analysis finds no substantial difference in the estimate, the OR
      reflects mainly the relative risk for disease occurrence. The proportion of
      genotype among putative cases at diagnosis can be estimated from prevalent cases
      by a logistic model, producing the OR adjusted for the interval from diagnosis.
      An incomplete-data case-control design is also applicable to adjust the
      prognostic effects. An actual prevalent case-control study on breast cancer is
      used to demonstrate the three approaches. They are useful to compensate the
      disadvantage of prevalent case-control studies.

PMID- 11579928
TI  - Validity and reliability of single-item questions about physical activity.
AB  - The Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by
      Monbusho (JACC Study) included in its self-administered questionnaires some
      single-item questions concerning physical activity. We examined the validity of
      the questions among 1,730 Japanese adults and the reliability of the questions
      among 1,075 Japanese adults. The validity of the sports and physical exercise
      questions was estimated by comparing the self-administered questionnaire
      responses with the time spent on the activity and the energy expenditure index
      for the previous 12-month period, elicited by the interviewing method used in the
      Japan Lifestyle Monitoring Study with a minor modification. The Spearman's rank
      correlation coefficients ranged from 0.43 to 0.60, showing moderate correlations.
      On the other hand, test-retest reliability was estimated by comparing the
      responses from two separate surveys conducted roughly one year apart. Weighted
      kappa coefficients of sports and physical exercise questions, classified
      according to sex and age, ranged from 0.39 to 0.56, showing moderate reliability;
      and those of a question about walking ranged from 0.25 to 0.39, showing fair
      reliability. We suggest that measuring physical activity level with these single
      item questions may be appropriate for establishing baseline data that reflects
      long-term physical activity in a large-scale cohort study targeting lifestyle
      related diseases.

PMID- 11579929
TI  - Japanese alcoholic beverage and all cause mortality in Japanese adult men.
AB  - This article examines whether an association is found between quantity of alcohol
      consumed and all cause mortality, and a relation is detected between types of
      alcoholic beverage and all cause mortality in Japanese male adults. A cohort
      study was performed in three towns located in two former coal mine areas and a
      rural area in Fukuoka. A mail survey was carried out between 1988 and 1990, and
      was extended in a follow-up period to 1995 (two towns) and 1999 (one town). 6,652
      Japanese men aged from 40 to 69 years responded to a questionnaire that included
      alcohol consumption and smoking habit. The data were analysed with Cox's
      proportional hazards model. As regards an association between all cause mortality
      and quantity of alcohol consumed, statistically significant relations were
      recognized in occasional drinkers and drinkers with less than 25g ethanol per day
      (hazard ratio= 0.71, 95% CI: 0.50-0.99; hazard ratio= 0.51, 95% CI: 0.29-0.88,
      respectively). With respect to drinkers with 25-50g/day and > or =50g/day, no
      significant relation was observed in the risk for all cause mortality. Comparing
      all cause mortality for daily drinkers and nondrinkers with respect to the
      beverage types, a risk was lower for daily drinkers than for nondrinkers with
      every type of beverage studied. In particular, there was a statistically
      significant adverse association for all cause mortality among subjects who
      reported drinking Japanese sake compared with nondrinkers (hazard ratio= 0.45,
      95% CI: 0.30-0.68). Alcohol consumption (particularly Japanese sake) is likely to
      be associated with a reduced hazardous ratio of all cause mortality.

PMID- 11579930
TI  - Covariation of cigarette smoking and other health-risk behaviors among Japanese
      high school students: a preliminary study.
AB  - This study aims to determine if cigarette smoking is associated with engaging in
      other health-risk behaviors among high school students in Japan. Self
      administered anonymous questionnaires were conducted in 1999 using a sample of
      1,466 students (male: 50.5%, female: 49.5%) in grades 10 through 12 at seven
      public senior high schools in urban areas of Okinawa, Japan. Health-risk
      behaviors studiedal included cigarette smoking, alcohol drinking, thinner use,
      sexual intercourse, suicidal ideation, nonuse of seat belts, physical inactivity,
      and weight loss practices. In the logistic regression models, controlled for
      sociodemographic variables, smoking was significantly associated with all health
      risk behaviors except physical inactivity. In particular, associations of alcohol
      drinking and sexual intercourse with smoking were strong. Among male students,
      statistically significant odds ratios existed for alcohol drinking, sexual
      intercourse, and nonuse of seat belts. Among female students, all of the odds
      ratios for health-risk behaviors were statistically significant, except for
      physical inactivity. Generally, the odds ratios of female students were higher
      than those of male students. In conclusion, high school students who smoked
      cigarettes in this study may be at higher risk for engaging in other health-risk
      behaviors. Particularly, alcohol drinking and sexual intercourse are more likely
      to co-occur with smoking. These findings suggest that smoking prevention programs
      should be integrated with other health-risk behaviors.

PMID- 11579931
TI  - Interplay of physical activity and vitamin D receptor gene polymorphism on bone
      mineral density.
AB  - The interplay of physical activity and vitamin D receptor (VDR) gene polymorphism
      in their effects on bone mineral density (BMD) was studied for 120 Japanese girls
      aged 18-19 years. BMD at distal radius in the group with the VDR genotype at the
      Apal site of Aa was significantly higher than that in the aa group, but this
      association disappeared in a group having the habit of physical activity. The Aa
      genotype gave a higher BMD than the aa genotype only in the group without the
      habit of physical activity. The habit of physical activity was associated with a
      higher BMD only in the aa genotype group. The similar interplay was observed in
      the VDR genotype at the TaqI site. We thus suggest that physical activity and VDR
      genotypes affect BMD in independent mechanism to give a saturated level of BMD.
      Higher dietary calcium intake tended to be associated with higher BMD only in the
      Aa genotype, suggesting that the calcium intake and VDR genotype affect BMD in a
      synergistic mechanism.

PMID- 11579932
TI  - The relationship between new stroke onset and serum thiocyanate as an indicator
      to cigarette smoking.
AB  - The case subjects were 67 stroke patients (27 males and 40 females, mean age
      65.7+/-7.1), who suffered from stroke attack and had participated in annual
      medical check-up between 1987 and 1988 at Oyabe Public Health Center. The
      controls, which were adjusted for sex, age and blood pressure level with the case
      subjects, were selected from participants attending their annual medical check-up
      in 1987-1988. The serum thiocyanate level of case subjects were significantly
      higher than that of controls (p<0.05). The usefulness of measurement of serum
      thiocyanate level as an indicator of smoking status was assessed by using
      multiple logistic regression analysis adjusting for body mass index, mean blood
      pressure, and serum cholesterol was found. An odds ratio of 3.00 (95% confidence
      interval: 1.06-8.48, p<0.05) in cerebral infarction. It is considered that serum
      thiocyanate may be useful as an indicator of smoking status to assess the
      relationship with stroke onset, especially for cerebral infarction.

PMID- 11579933
TI  - Natural killer activity and its changes among participants in a smoking cessation
      intervention program--a prospective pilot study of 6 months' duration.
AB  - We examined the effect of smoking cessation on natural killer (NK) activity of
      peripheral blood lymphocytes in terms of a prospective study of 27 Japanese
      subjects who participated in a smoking cessation intervention program. This
      program was delivered by means of group-counseling offering 7 sessions of about 2
      hours over 6 months to help smokers to discontinue the habit. Thirteen subjects
      ceased smoking (quitters), while 14 continued to smoke (cigarette smokers). NK
      activity before the intervention was correlated positively with age (correlation
      coefficient=0.46, P<0.05). NK activity remained almost constant among quitters,
      comparing the activity before and after the intervention, while it decreased
      among cigarette smokers although it was not statistically significant. In the
      subgroup analysis, NK activity increased among those aged less than 65 years, or
      urine cotinine levels over 800 ng/ml before the intervention, especially among
      quitters, but there were no statistical significances. Multiple regression
      analysis showed changes in NK activity were correlated significantly only with
      age (standard regression coefficient=-0.44, P<0.05). These findings suggest that
      smoking cessation intervention programs might have been more effective for
      younger than elder subjects in consideration of NK activity.

PMID- 11579934
TI  - An extraterrestrial impact at the Permian-Triassic boundary?

PMID- 11579935
TI  - Mitigating GHGs in developing countries.

PMID- 11579936
TI  - Short-term trials and long-term effects.

PMID- 11579937
TI  - Advice for a better OTA.

PMID- 11579938
TI  - Comparing human genome mapping data.

PMID- 11579939
TI  - Cabergoline, a hopeful medicine for prolactinomas and non-tumoral
      hyperprolactinemia.

PMID- 11579940
TI  - Association of gene polymorphism of polymeric immunoglobulin receptor and IgA
      nephropathy.

PMID- 11579941
TI  - Transthoracic needle aspiration: a useful technique to detect causative organisms
      of pneumonia.

PMID- 11579942
TI  - Hyponatremia in elderly patients.

PMID- 11579943
TI  - C282Y and H63D mutations in the HFE gene have no effect on iron overload
      disorders in Japan.
AB  - OBJECTIVE: The gene responsible for hereditary hemochromatosis close to the human
      leukocyte antigen A locus was previously identified and designated as HFE. This
      study was performed to evaluate the clinical significance of two mutations, C282Y
      and H63D of HFE, in Japanese patients with hepatic iron overload. PATIENTS AND
      METHODS: We examined C282Y and H63D in 11 patients with primary hemochromatosis,
      94 patients with chronic hepatitis C, 54 patients with miscellaneous liver
      diseases, and 151 healthy volunteers. The HFE gene region of DNA samples
      extracted from peripheral leukocytes was amplified by polymerase chain reaction.
      Restriction enzyme analysis was performed using SnaBI for C282Y and BclI for
      H63D. Direct sequence analysis was then performed when products suggested the
      presence of a mutation. RESULTS: All the subjects studied were free from C282Y.
      None of the patients with hemochromatosis had H63D. One patient with chronic
      hepatitis C was homozygous, and 4 patients were heterozygous for H63D. Two
      patients with alcoholic liver disease were heterozygous for H63D. The prevalence
      of chromosomes with H63D was 6/188 (3.2%) in patients with chronic hepatitis C,
      2/108 (1.9%) in patients with miscellaneous liver diseases, and 8/302 (2.6%) in
      healthy volunteers. These differences were not significant. CONCLUSION: Our
      results suggested that neither C282Y nor H63D in HFE affect Japanese patients
      with hemochromatosis or chronic hepatitis C.

PMID- 11579944
TI  - Comparison of the effects of cabergoline and bromocriptine on prolactin levels in
      hyperprolactinemic patients.
AB  - OBJECTIVE: It is well known that bromocriptine has a suppressive effect on the
      prolactin release in hyperprolactinemic patients. But it also has some adverse
      effects. The new, long-acting dopaminergic drug, cabergoline, has been reported
      to be an effective agent in these patients. However, there are relatively few
      reports comparing the beneficial and adverse effects of these drugs in the
      treatment of hyperprolactinemic patients. Therefore, here we studied and compared
      the efficacy and tolerability of cabergoline with bromocriptine in
      hyperprolactinemic patients. PATIENTS: Seventeen patients (7 with
      microprolactinoma, 4 with macroprolactinoma, 6 with idiopathic
      hyperprolactinemia) were given bromocriptine at a dose of 2.5 mg (or 5 mg for
      macroprolactinomas) twice daily, and 17 patients (8 with microprolactinoma, 4
      with macroprolactinoma, 5 with idiopathic hyperprolactinemia) were given
      cabergoline at a dose of 0.5 mg twice weekly for 12 weeks. RESULTS: At the end of
      the study, the prolactin reduction was significantly greater in the cabergoline
      group than in the bromocriptine group (-93 vs. -87.5 %, respectively, p < 0.05).
      Normalization of prolactin levels was achieved in 10 of 17 patients (59%) in the
      bromocriptine group, and in 14 of 17 patients (82%) in the cabergoline group (p =
      0.13). Two patients (50%) with macroprolactinoma in the bromocriptine group and
      three patients (75%) with macroprolactinoma in the cabergoline group demonstrated
      a normalization of their serum prolactin levels. Adverse events were noted in 53%
      of bromocriptine patients and in 12% of cabergoline patients (p < 0.01).
      CONCLUSION: These data indicate that cabergoline is a very effective agent for
      lowering the prolactin levels in hyperprolactinemic patients and that it appears
      to offer considerable advantage over bromocriptine in terms of efficacy and
      tolerability.

PMID- 11579945
TI  - Cellular crescents and segmental glomerular necrosis in IgA nephropathy are
      indicative of the beneficial effects of corticosteroid therapy.
AB  - OBJECTIVE: Recent reports have revealed that corticosteroid (PSL) therapy has a
      long-term beneficial effect for stabilization of renal function in progressive
      IgA nephropathy. PATIENTS AND METHODS: We analyzed serum creatinine (Cr), daily
      proteinuria and the results of other routine laboratory examinations during a
      short-term course of PSL therapy in 28 cases of progressive IgA nephropathy. The
      cases were divided into two groups according to changes in renal function during
      the PSL treatment period: group I (15 cases), improved renal function; group II
      (13 cases), no significant change in renal function. RESULTS: In group I, serum
      Cr and proteinuria were significantly decreased, with maximum effects observed at
      3 months of PSL therapy, and remained low during the period of treatment. In
      contrast, group II showed no significant changes in serum Cr levels during the
      period of therapy, although proteinuria was transiently decreased after 3 months
      of therapy. Histologically, cellular/fibrocellular (C/F) crescents and/or
      segmental glomerular necrosis (SGN) occurred with a significantly higher
      incidence in group I (87%) than in group II (46%) (p < 0.05). CONCLUSIONS: These
      results suggested that the early response to PSL in reducing serum Cr and
      proteinuria by 3 months of treatment may be clinically useful to predict the
      prognosis of IgA nephropathy and that C/F crescents and/ or SGN may be
      histologically indicative of the beneficial effects of PSL therapy in IgA
      nephropathy.

PMID- 11579946
TI  - Association of gene polymorphism of polymeric immunoglobulin receptor and IgA
      nephropathy.
AB  - OBJECTIVE: In order to explore the possibility that genetic predisposition to
      dysfunction of mucosal immunity and the IgA processing pathway plays a role in
      the pathogenesis of mesangial IgA1 deposition in IgAN, we examined the possible
      association of the gene polymorphism of pIgR in the patients with and without
      IgAN. SUBJECTS AND METHODS: Genomic DNA of peripheral blood cells was isolated
      from 372 individuals including 172 histologically confirmed IgAN patients.
      Segments of the pIgR gene were PCR amplified and restriction fragment length
      polymorphism was determined as A1 and A2 with and without Pvu II site,
      respectively. RESULTS: The pIgR genotype distribution was significantly different
      between the patients with IgAN and those without IgAN. Allele frequency of A2 was
      higher in IgAN than in other renal diseases (A1 and A2; 0.516 and 0.484 in IgAN,
      0.641 and 0.359 in others, chi2 = 9.84, P = 0.0017, Odds ratio = 1.71). Moreover,
      the subjects with A2A2 genotype were associated with a relatively low level of
      serum IgA only in the patients with IgAN but not in other renal diseases. The
      difference of allele frequencies was more remarkable in the patients with a serum
      IgA level of less than 300 mg/dl (A1 and A2; 0.439 and 0.561 in IgAN, 0.702 and
      0.298 in others, chi2 = 12.44, P = 0.0004, Odds ratio = 3.01). CONCLUSION: This
      is the first demonstration of the pIgR gene polymorphisms in IgAN which are
      associated with its clinical phenotype. Gene polymorphisms of pIgR may be
      candidate genetic markers of susceptibility to IgAN.

PMID- 11579947
TI  - Efficacy of transthoracic needle aspiration in community-acquired pneumonia.
AB  - OBJECTIVE: To evaluate the indications, efficacy, and safety of transthoracic
      needle aspiration (TNA) in diagnosing community-acquired pneumonia (CAP).
      METHODS: TNA procedure was performed using an ultrathin needle with
      ultrasonography and/or computed tomography. The aspirate samples were Gram
      stained and sent for cultures. The results were compared with those from
      conventional microbiological studies. PATIENTS: Sixty patients with CAP who were
      admitted to the hospital and were studied prospectively between July 1994 and
      June 1999 were included in the study. RESULTS: TNA culture was positive in 30
      cases (50.0%). Streptococcus pneumoniae was the most frequently isolated
      pathogen, followed by the Streptococcus milleri group, and anaerobes. The results
      of TNA were consistent with those of quantitative sputum cultures in 9 patients
      and with those of blood cultures in 4. Complications arose in 3 patients who
      developed small to moderate pneumothorax. CONCLUSIONS: TNA is a safe procedure
      with a good diagnostic yield. In particular, anaerobes or microaerophils such as
      the S. milleri group were highly detectable by TNA. The results obtained by TNA
      were highly consistent with those obtained by the gold standard methods. Combined
      with conventional methods, TNA is considered highly useful for determining the
      etiology of CAP.

PMID- 11579948
TI  - Clinical characteristics of B-cell lymphoma-associated hemophagocytic syndrome (B
      LAHS): comparison of CD5+ with CD5- B-LAHS.
AB  - OBJECTIVE: B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS) has been
      increasingly reported in Asia and is regarded as a variant of intravascular
      lymphomatosis (IVL). Recently CD5 was reported to be expressed in some cases of
      diffuse large cell lymphoma and IVL. We therefore examined the expression of CD5
      on lymphoma cells in B-LAHS and compared the clinical and laboratory data between
      CD5+ and CD5- B-LAHS. METHODS: The expression of CD5 on lymphoma cells was
      examined using flow cytometry and immunohistochemical analysis of paraffin
      sections. The clinical records were reviewed to characterize clinical features.
      PATIENTS: Twelve patients with B-LAHS; ten men and two women, age ranging from 41
      to 82 years (median, 63.5 years) were included in this study. RESULTS: B-LAHS is
      characterized by fever and hepatosplenomegaly without lymphadenopathy at the
      initial presentation. Histological examination showed hemophagocytosis and
      infiltration of lymphoma cells in the bone marrow, and in some cases
      intravascular proliferation of lymphoid cells characteristic of IVL. All patients
      showed increased levels of lactate dehydrogenase, C-reactive protein, ferritin
      and soluble interleukin-2 receptor. In eight of the twelve patients, lymphoma
      cells were positive for CD5. But no differences were observed in the clinical or
      laboratory findings between CD5+ B-LAHS and CD5- B-LAHS. CONCLUSION: No clinical
      differences were observed between CD5+ B-LAHS and CD5- B-LAHS. Further studies
      are required to elucidate the differences in pathogenesis between these two
      subgroups of B-LAHS.

PMID- 11579949
TI  - Interstitial pneumonia accompanying ulcerative colitis.
AB  - We report a patient with ulcerative colitis complicated with idiopatic
      interstitial pneumonia, in whom the etiology of interstitial pneumonia was
      unknown, but immunological disturbance might have been involved. There are many
      complications with ulcerative colitis, but interstitial pneumonia is quite rare
      and its prognosis is quite poor. Antibiotic and steroid treatment were given
      under respiration supported therapy, but no response could be obtained. In the
      treatment of patients with ulcerative colitis, we must be mindful of interstitial
      pneumonia because the prognosis is quite poor.

PMID- 11579950
TI  - An inferior mesenteric-caval shunt via the internal iliac vein with portosystemic
      encephalopathy.
AB  - We report here a case of an unusual extrahepatic portosystemic venous shunt in a
      37-year-old woman without liver cirrhosis or portal hypertension, who developed
      portal systemic encephalopathy. Angiography demonstrated an inferior mesenteric
      caval shunt characterized by the presence of direct communication of the inferior
      mesenteric vein with the left internal iliac vein. After the treatment with
      percutaneous transcatheter embolization of the shunt via a femoral vein approach
      using coils, she had no episode of portal systemic encephalopathy.

PMID- 11579951
TI  - Spontaneous regression of hepatic adenoma in a patient with glycogen storage
      disease type I after hemodialysis: ultrasonographic and CT findings.
AB  - A 23-year-old woman was admitted to our hospital with recurrent gouty arthritis.
      Laboratory findings showed hypoglycemia, lactic acidosis, hyperlipidemia, and
      hyperuricemia, with normal values of serum alfa-fetoprotein (AFP) and protein
      induced by vitamin K absence (PIVKA-II). A diagnosis of glycogen storage disease
      type I (GSD-type I) was made on the basis of the laboratory data, liver biopsy
      findings, and partially deficient thrombocyte glucose-6-phosphatase (G-6-Pase)
      activity. Ultrasonography and computed tomography revealed multiple focal hepatic
      masses. Biopsied specimens of the lesion demonstrated a hepatic adenoma, which
      changed in appearance in the relatively short period between echography and
      computed tomography. This interesting phenomenon may highlight the importance for
      careful follow-up of hepatic adenomas, because of the potential of rupture,
      hemorrhage, or malignant transformation. During follow-up, the present patient
      received hemodialysis due to renal failure, and the adenoma regressed
      spontaneously after 8 years. Included are diagnostic images, demonstrating the
      association of hepatic adenoma and GSD-type I.

PMID- 11579952
TI  - Pneumatosis cystoides intestinalis treated with hyperbaric oxygen therapy:
      usefulness of an endoscopic ultrasonic catheter probe for diagnosis.
AB  - A 67-year-old woman was admitted to our hospital with a complaint of abdominal
      pain. Barium enema examination and colonoscopy showed numerous round polypoid
      lesions covered with normal mucosa in the area from the ascending colon to the
      splenic flexure. Endoscopic ultrasound examination with an ultrasonic catheter
      probe revealed a strong echo with distal acoustic shadowing in the third layer of
      the diseased colonic wall, which suggested the presence of gas in the submucosa.
      The gaseous cysts disappeared completely after hyberbaric oxygen therapy at 2 to
      3 atmospheres absolute (60 minutes, twice a day) for 30 consecutive days.

PMID- 11579953
TI  - Acute pericarditis associated with 5-aminosalicylic acid (5-ASA) treatment for
      severe active ulcerative colitis.
AB  - A 17-year-old male who had been diagnosed with ulcerative colitis was prescribed
      80 mg prednisolone and 1,500 mg 5-aminosalicylic acid (5-ASA) per day. Two weeks
      after initiating therapy, he was referred to our hospital for evaluation of chest
      pain and high fever. Electrocardiography (ECG) showed ST elevation in limb and
      precordial leads. Chest pain with high fever and ECG changes were resolved after
      5-ASA was discontinued. Three weeks later, the administration of a low dose of 5
      ASA was associated with the immediate recurrence of pericarditis associated with
      chest pain, suggesting a hypersensitive reaction to 5-ASA in this patient.

PMID- 11579954
TI  - Primary pulmonary hypertension with severe systemic hypertension, Raynaud's
      phenomenon and relative polycythemia.
AB  - A 32-year-old Japanese man was hospitalized for evaluation of unconsciousness. He
      was diagnosed as having primary pulmonary hypertension (PPH) with severe systemic
      hypertension, Raynaud's phenomenon and relative polycythemia. Hemostatic studies
      revealed increased coagulation and decreased fibrinolysis, similar to findings of
      chronic disseminated intravascular coagulation (DIC). Although activation of
      coagulation and systemic hypertension were improved after treatment with
      phlebotomy and administration of nifedipine, enerapril and warfarin, pulmonary
      hypertension was unchanged, suggesting that irreversible change had already
      occurred in the pulmonary arteries. Those complications could modify the process
      of pulmonary hypertension by inducing a hyperviscosity state.

PMID- 11579955
TI  - Breast cancer presenting with the syndrome of inappropriate secretion of
      antidiuretic hormone after simple mastectomy.
AB  - A 71-year-old woman showed disorientation 7 days after simple mastectomy for
      right breast cancer. Computed tomography of the brain was normal. The level of
      serum sodium was very low (110 mEq/l), while the urine sodium level was normal.
      The osmolality of urine was higher (342 mosmol/kg) than that of serum (220
      mosmol/kg). These data suggested a syndrome of inappropriate secretion of
      antidiuretic hormone. A fluid restriction, infusion of hypertonic saline and
      administration of diuretics gradually increased the level of serum sodium.
      Subsequently, disorientation disappeared. This is a rare case of the syndrome of
      inappropriate secretion of antidiuretic hormone caused by simple mastectomy, a
      relatively minor surgical procedure.

PMID- 11579956
TI  - Idiopathic giant cell granulomatous hypophysitis with hypopituitarism, right
      abducens nerve paresis and masked diabetes insipidus.
AB  - A 38-year-old man presented with headache, fever, and double vision associated
      with right abducens nerve paresis. He had neither nuchal rigidity nor visual
      field defect. Laboratory data revealed elevated erythrocyte sedimentation rate
      (ESR), eosinophilia, and lymphocytic pleocytosis in the cerebrospinal fluid
      (CSF). Provocation tests of pituitary hormones showed partial hypopituitarism.
      Magnetic resonance imaging (MRI) revealed swelling of the hypophysis and a mass
      lesion expanding into the right cavernous sinus. The supplement dose of
      dexamethasone for hypothalamic hypocortisolism manifested diabetes insipidus.
      Biopsy, carried out through the transsphenoidal approach, revealed giant cell
      granuloma. Systemic granulomatous diseases were ruled out, and the lesion was
      considered to be idiopathic giant cell granulomatous hypophysitis. Right abducens
      nerve paresis, diabetes insipidus and dysfunction of the anterior lobe were
      amended by the treatment with prednisolone for 4 months, and findings of the
      pituitary gland and stalk were normalized. The present case shows that
      glucocorticoid has an effect on amendment of idiopathic giant cell granulomatous
      hypophysitis.

PMID- 11579957
TI  - 17alpha-hydroxylase deficiency accompanied by adrenal myelolipoma.
AB  - A 45-year-old woman was admitted because of hypertension and hypokalemia. Primary
      amenorrhea from birth was noted. Plasma renin activity (PRA), 17alpha
      hydroxyprogesterone and androgen levels were low, but progesterone, 11
      deoxycorticosterone, corticosterone and adrenocorticotropic hormone (ACTH) were
      elevated, resulting in a diagnosis of 17alpha-hydroxylase deficiency. Abdominal
      magnetic resonance imaging revealed a round mass in the left adrenal region, the
      specimen of which was diagnosed as myelolipoma. After removal of the tumor, the
      blood pressure, serum potassium and hormone levels were unchanged, indicating an
      adrenal non-functioning tumor. Excessive ACTH secretion over a long period may
      stimulate the development of adrenal myelolipoma.

PMID- 11579958
TI  - Renal cell carcinoma with  skull base metastasis preceded by paraneoplastic signs
      in a chronic hemodialysis patient.
AB  - A 59-year-old man who had received chronic hemodialysis developed left occipital
      pain and hypoglossal nerve palsy. He was diagnosed as having skull base
      metastasis from renal cell carcinoma related to acquired cystic kidney.
      Retrospective analysis revealed the patient had had elevated serum C-reactive
      protein and alkaline phosphatase levels before the symptoms appeared.
      Radiotherapy to the skull base relieved the pain. Finally he died with
      generalized metastases. Serum interleukin-6 levels measured during admission had
      been elevated, and interleukin-6 mRNA was detected in the autopsy specimen of
      renal cell carcinoma. Interleukin-6 might be involved in the etiology of
      paraneoplastic signs.

PMID- 11579959
TI  - IgA-kappa type multiple myeloma affecting proximal and distal renal tubules.
AB  - A 45-year-old male was admitted because of chest pain, lumbago, and bilateral
      ankle pain. Examination disclosed hypophosphatemic osteomalacia, acquired Fanconi
      syndrome, and abnormalities in distal nephron such as distal renal tubular
      acidosis and renal diabetes insipidus. Further exploration revealed IgA kappa
      multiple myeloma excreting urinary Bence Jones protein (kappa-light chain). Renal
      biopsy revealed thick basement membranes and elec-tron-dense crystals in proximal
      tubular epithelial cells. Immunofluorescent studies revealed deposition of kappa
      light chain in renal tubular epithelial cells that caused the renal tubular
      damage. Although the osteomalacia was relieved by medical treatment, the urinary
      Bence Jones protein and the renal tubular defects were not improved by the
      chemotherapy for the myeloma. The patient died of exacerbation of multiple
      myeloma at 50 years of age.

PMID- 11579960
TI  - Massive rhabdomyolysis and acute renal failure after acetonitrile exposure.
AB  - A case of systemic rhabomyolysis after acetonitrile exposure is reported. A 35
      year-old previously healthy man suffered from vomiting, convulsion and
      consciousness loss 15 hours after exposure to acetonitrile. Since acetonitrile is
      known to be metabolized into cyanide, antidote therapy against cyanide poisoning
      was given. On admission, pain and all-over muscle swelling were marked. Although
      the initial therapy was effective, rhabdomyolysis and then acute renal failure
      developed. Renal function improved very slowly after six weeks of hemodialysis,
      but atrophy of the muscles remained. The rhabdomyolysis may have been caused by
      toxicity of the cyanide itself in combination with hypoxia and convulsion.

PMID- 11579961
TI  - Severe inclusion body myositis with interstitial pneumonia.
AB  - We report a patient with a severe inclusion body myositis (IBM). His illness was
      unusual in terms of a rapid progression, high creatine kinase levels, and
      complication with interstitial pneumonia. He responded well to immunosuppressive
      agents such as corticosteroids, cyclosporin A, cyclophosphamide, and
      immunoglobulin. The present patient indicates the wide range of the disease, and
      that immunosuppressive agents may be useful for treatment of IBM.

PMID- 11579962
TI  - Continuous hemodiafiltration for disseminated intravascular coagulation and shock
      due to amniotic fluid embolism: report of a dramatic response.
AB  - We describe a 27-year-old woman with disseminated intravascular coagulation and
      shock due to amniotic fluid embolism after Caesarean section who responded well
      to continuous hemodiafiltration (CHDF) therapy. The effectiveness of CHDF in
      treating amniotic fluid embolism is also discussed.

PMID- 11579963
TI  - Neurofibromatosis type 1 with basilar artery fusiform aneurysm manifesting
      Wallenberg's syndrome.
AB  - A case of neurofibromatosis type 1 (NF1) manifesting Wallenberg's syndrome and
      fusiform aneurysm of the basilar artery is reported. The patient suddenly
      developed dysarthria, walking difficulty and sensory disturbance. Neurological
      examination suggested Wallenberg's syndrome and MR imaging confirmed an ischemic
      lesion at the left lateral medulla oblongata. Cerebral angiography revealed a
      fusiform aneurysm at the middle portion of the basilar artery. However, there was
      no occlusive change in either the posterior inferior cerebellar artery or the
      vertebral artery. The clinical and radiological features are discussed together
      with a review of NF1 cases with intracranial aneurysms in the literature.

PMID- 11579964
TI  - Lupus anticoagulant in myasthenia gravis associated with IgM gammopathy.
AB  - The plasma of a patient with myasthenia gravis had strong lupus anticoagulant
      activity and his IgM paraprotein displayed non-specific inhibition to coagulation
      factors IX, XI, XII, prekallikrein, and high molecular weight kininogen. He was
      placed on prednisolone, which resulted in improvement in his myasthenic symptoms,
      but the prolongation of APTT and macroglobulinemia remained. Double filtration
      plasmapheresis successfully decreased the serum IgM level from 1,190 mg/dl to 375
      mg/dl and APTT improved from 58 s to 38 s. Myasthenia gravis is frequently
      associated with other autoimmune diseases, but the association with lupus
      anticoagulant and IgM gammopathy is rare.

PMID- 11579965
TI  - Brain metastases of malignant melanoma showing unbalanced whole arm chromosomal
      translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10) in a Japanese
      patient.
AB  - Since malignant melanoma is a rare malignancy in Japan, little is known about the
      cytogenetic abnormalities in Japanese patients. We report a case of malignant
      melanoma showing complex chromosomal abnormalities. A 70-year-old woman was
      admitted to our hospital because of anorexia, delirium, and right hemiplegia.
      Cranial CT disclosed several metastatic brain tumors. Multiple subcutaneous and
      intra-abdominal metastases were also found. A diagnosis of metastatic malignant
      melanoma was made by biopsy of a subcutaneous tumor. Chromosomal analysis of the
      tumor cells disclosed complex karyotypic abnormalities including novel unbalanced
      whole arm translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10).

PMID- 11579966
TI  - Dizziness when eating: an unusual isolated presentation of cerebral venous
      thrombosis.
AB  - A previously healthy 60-year-old man had a two-year history of dizziness or
      faintness when eating but not when drinking. MRI of the brain detected deep
      venous dilatation, and digital subtraction cerebral angiography showed superior
      sagittal sinus thrombosis. These symptoms were completely resolved after the
      daily administration of 200 mg ticlopidine for four weeks. The pathomechanism of
      this unusual presentation is speculated episodic congestion of the jugular venous
      drainage during mealtime due to an increase in the circulatory volume of the
      external carotid-jugular system.

PMID- 11579967
TI  - Rheumatoid factor positive hypertrophic cranial pachymeningitis in association
      with hypopituitarism and multiple cranial nerve palsies.
AB  - This is the first report of a patient presenting with rheumatoid factor (RF)
      positive hypertrophic cranial pachymeningitis (HCP) in association with
      hypopituitarism and multiple cranial nerve palsies. Our patient developed palsies
      of the left II and III, bilateral VI and VII, and right IX, X, and XII cranial
      nerves. A stimulation test showed hypopituitarism due to hypothalamic failure.
      The patient was seropositive for RF but had no multiple joint pain or
      deformities. Magnetic resonance imaging (MRI) showed thickened dura of the sellar
      and parasellar region, hypothalamus, bilateral cavernous sinuses and the
      tentorium all of which were enhanced by gadolinium (Gd). Treatment with
      prednisone improved clinical symptoms and MRI findings concomitant with reduction
      of RF titer. Although the exact mechanism of HCP has not been clearly elucidated,
      the present case suggests an autoimmune mechanism associated with RF.

PMID- 11579968
TI  - Stiff-person syndrome associated with cerebellar ataxia and high glutamic acid
      decarboxylase antibody titer.
AB  - Glutamic acid decarboxylase (GAD) is the main target of humoral autoimmunity in
      patients with insulin-dependent diabetes mellitus (IDDM) and stiff-person
      syndrome. We reviewed the case of a 46-year-old woman who had cerebellar ataxia
      before getting stiff-person syndrome and IDDM with high anti-GAD autoantibody
      titers. This was a rare case in which there were both the clinical symptoms of
      stiff-person syndrome and cerebellar ataxia. In western blot analysis her serum
      reacted with 65-kDa proteins from rat cerebellum, cerebral cortex, and spinal
      cord. Autoantibodies to GAD may cause functional impairment of gamma-aminobutyric
      acid (GABA) neurons in the spinal cord as well as in the cerebellum.

PMID- 11579969
TI  - Rapidly progressive tabes dorsalis associated with selective IgA deficiency.
AB  - Tabes dorsalis is uncommon and progresses slowly from infection to clinical
      manifestation. We report a rare case of rapidly progressive tabes dorsalis
      associated with selective IgA deficiency (sIgAD). A 28-year-old man was
      hospitalized with lightning back pain, nausea, and bladder bowel dysfunction.
      Serum and cerebrospinal fluid (CSF) revealed high titers of Treponema pallidum
      antibody, and the serum IgA level was less than 5 mg/dl. Thl-dominant cytokine
      expression was observed, as is usually seen in neurosyphilis. He was treated with
      Ceftriaxone and CSF pleocytosis disappeared. We postulate sIgAD influenced the
      atypical rapid clinical course of tabes dorsalis in this patient.

PMID- 11579970
TI  - Successful treatment of multicentric Castleman's disease with intracranial and
      retroperitoneal tumors.

PMID- 11579971
TI  - Fibromuscular dysplasia.

PMID- 11579973
TI  - Mechanical failures as a contributing cause to motor vehicle accidents South
      Africa.
AB  - Over the past decades motor vehicles became the primary mode of transportation in
      developing countries. At the same time an improvement in automotive engineering
      and manufacturing as well as the phenomena of urbanisation have resulted in more
      vehicles spending more time on the road at higher speeds. Invariably this leads
      to driving scenarios where safety critical manoeuvres have to be performed that
      rely on the mechanical condition of the vehicles. In developing countries, where
      economic realities force the population to make use of older and less reliable
      vehicles, the risk of accidents caused by some sort of mechanical failure
      increases. The casualty rate (events causing death and/or serious injuries) for
      road traffic accidents in South Africa is amongst the highest in the world. This
      trend has persisted with little variation over the years, despite the efforts of
      local road safety organisations and research institutes to decrease them. The
      main goal of this study was to establish the contribution of mechanical failures
      to motor vehicle accidents, and furthermore, to compare it with international
      trends. Data obtained from accident response units (ARU) indicate that tyres and
      brakes were the main contributors to mechanical failures resulting in accidents
      in the Pretoria region (Gauteng Province). However, the reported percentage of
      approximately 3% is comparable to similar statistics from developed countries.
      Detailed information on the condition of road-going vehicles was then collected
      in this area. The roadside survey (potential mechanical defect tests (PMDT))
      indicated that 40% of the vehicles surveyed on the suburban road and 29% of the
      vehicles surveyed on the highway had mechanical defects that contravened current
      road and traffic regulations in South Africa and may, therefore, be at risk of
      causing an accident due to a mechanical failure. In the Minibus (taxi) survey,
      large irregularities in tyre inflation pressure were identified as a cause of
      concern. The main conclusion from this work is that tyres and brakes are the two
      most dominant components that contribute to the mechanical defects causing
      accidents, with overloading an additional factor to consider. It is important to
      acknowledge that these three factors can easily be monitored during simple
      roadside inspections.

PMID- 11579972
TI  - Cannabis use and traffic accidents in a birth cohort of young adults.
AB  - OBJECTIVE: to examine linkages between cannabis use and traffic accident risks in
      a birth cohort of 907 young New Zealanders studied from 18 to 21 years. METHODS:
      during the course of a 21-year longitudinal study of a birth cohort of 907 New
      Zealand born children information was gathered on (a) annual frequency of
      cannabis use over the period from 18 to 21 years; (b) annual rates of traffic
      accidents during the period 18-21 years; (c) measures of driver behaviours and
      characteristics. The association between cannabis use and traffic accident risk
      was examined among the 907 sample members who reported driving a motor vehicle
      between the ages of 18 and 21 years. RESULTS: there were statistically
      significant relationships between reported annual cannabis use and annual
      accident rates. This association was present only for 'active' accidents in which
      driver behaviours contributed to the accident; those using cannabis more than 50
      times per year had estimated rates of active accidents that were 1.6 (95% CI 1.2
      2.0) times higher than the rate for non-users. However, statistical control for
      driver behaviours and characteristics related to cannabis use (drink driving
      behaviour; risky/illegal driving behaviours; driver attitudes; gender) eliminated
      the association between cannabis use and traffic accident risks. CONCLUSIONS:
      although cannabis use was associated with increased risks of traffic accidents
      among members of this birth cohort, these increased risks appear to reflect the
      characteristics of the young people who used cannabis rather than the effects of
      cannabis use on driver performance.

PMID- 11579974
TI  - A simple method for identifying and correcting crash problems on urban arterial
      streets.
AB  - Urban arterials by their nature carry heavy traffic volumes and generate large
      numbers of motor vehicle crashes. The present study involved review of police
      crash reports to identify precrash events and driver actions for a sample of
      crashes on urban arterials and describes a method for reducing such crashes based
      on analyses of collision patterns and identification of locations with excessive
      numbers of crashes of a particular type. Police-reported crash data were obtained
      for three urban arterials in the Washington, DC metropolitan area. A total of
      2,013 crash reports were analyzed. Seven crash types accounted for nearly 90% of
      these reports. On each arterial studied, several locations with excessive numbers
      of crashes of a particular type were identified, and corresponding engineering
      countermeasures were recommended. Differences between the approach employed in
      this study and traditional blackspot analyses are discussed.

PMID- 11579975
TI  - A nationwide survey of self-reported red light running: measuring prevalence,
      predictors, and perceived consequences.
AB  - A United States probability sample of 880 licensed drivers participated in a
      telephone survey of red light running perceptions and behaviors. Despite most
      drivers believing red light running was problematic and dangerous, approximately
      one in five respondents reported running one or more red lights when entering the
      last ten signalized intersections. Among several demographic and attitude
      variables, only age group predicted recent red light running. Specifically,
      younger respondents were more likely to be violators. Drivers also reported being
      more likely to run red lights when alone, and were typically in a hurry when
      speeding up to be beat red lights. Contrary to expectations, frustration was not
      as important for predicting red light running as it was for other driving
      behaviors, such as speeding, tailgating, weaving, and gesturing angrily at
      others. Additionally, drivers perceived and received few consequences for running
      red lights. Less than 6% had received a traffic ticket for red light running and
      most believed that police would catch less than 20% of violators. Slightly more
      than one in ten had been involved in a red light running crash. Respondents most
      commonly suggested legal initiatives to reduce red light running. Accordingly, we
      recommend traffic safety experts pursue interventions that apply immediate and
      consistent negative consequences to violators to change the public's red light
      running perceptions and behavior.

PMID- 11579976
TI  - Analysis of progress in road safety in ten European countries.
AB  - Classic models for the long-term forecasting of the number of fatalities in road
      accidents are based on a decreasing exponential form of the rate of fatalities
      per vehicle x km. We decided to extend this simple model to incorporate
      intervention functions connected with the major safety measures introduced and to
      replace the deterministic trend by a stochastic one. Harvey's structural model,
      known as the local linear trend model, is applied to ten European countries. The
      relationship between the slope of this trend and the elasticity in terms of the
      number of vehicles x km yields an indicator of the rate of progress in road
      safety made in the different countries. The average rate is around -6% per annum,
      with a minimum of -4.5% and a maximum of -13.5% for Spain in 1994. Europe's road
      systems can thus absorb a 6% increase in traffic per annum while maintaining the
      number of fatalities constant.

PMID- 11579977
TI  - Protecting the child's abdomen: a retractable bicycle handlebar.
AB  - A surveillance system in the Emergency Department of a level 1 pediatric trauma
      center previously identified minor bicycle crashes as a cause of serious child
      abdominal injury. A discordancy exists between the apparently minor circumstances
      and serious injuries sustained by child bicyclists who impact bicycle handlebars.
      The objective of this work was to redesign the bicycle handlebar to reduce the
      forces transmitted to the child's abdomen during an impact with the handlebars. A
      retractable handlebar consisting of a spring-mass-damper system was designed to
      retract and absorb the majority of energy at impact (Patent pending). Because the
      child remains in contact with the bar after impact, the retracting system also
      includes a mechanism to damp the outward motion of the handlebar. This prototype
      will reduce the forces at impact by approximately 50% in a collision similar to
      those discussed above. A unique methodology of translating research findings into
      product design produced a novel handlebar that absorbs significant energy that
      otherwise would be transferred to the child's abdomen when impacting the
      handlebar.

PMID- 11579978
TI  - Novice drivers' accidents and violations--a failure on higher or lower
      hierarchical levels of driving behaviour.
AB  - The study compared accident and offence rates of 28 500 novice drivers in
      Finland. The purpose was to study differences in accident and offence rates
      between male and female novice drivers of different age. The drivers reported in
      a mailed questionnaire, how many accidents they had been involved in and how much
      they had driven during their whole driving career. All the drivers had a driving
      experience of 6-18 months. Information about offences for a 2-year period was
      obtained from an official register of drivers' licences. The drivers were
      classified into three age brackets: 18-20, 21-30 and 31-50 years. The effect of
      driving experience was controlled by dividing the drivers into different mileage
      brackets. The data was analysed and the results were discussed in the framework
      of the hierarchical model of driving behaviour. Young novice drivers and
      especially young male drivers showed more problems connected to the higher
      hierarchical levels of driving behaviour than middle-aged novice drivers. The
      number of accidents and offences was highest among the young males and their
      accidents took place more often at night than female or older drivers' accidents.
      Female drivers showed more problems connected to the lower hierarchical levels of
      driving behaviour, e.g. problems in vehicle handling skills. Ways of measuring
      accident risk of different driver groups were also discussed, as well as the
      usefulness and reliability of self-reports in accident studies.

PMID- 11579979
TI  - Alcohol/drug abuse, driving convictions, and risk-taking dispositions among
      trauma center patients.
AB  - The objective of this study was to evaluate the relationship between alcohol/drug
      abuse diagnoses, driving convictions (speeding, reckless driving, impaired
      driving, license violations), and risk-taking dispositions among a series of
      injured drivers admitted to a trauma center. The driving records of 778 patients
      were linked to diagnoses of psychoactive substance use disorders (PSUDs),
      admission blood alcohol concentration (BAC), mode of injury, and results of a
      risk-taking disposition survey. Twenty-nine percent of patients had one or more
      convictions in the 3 years before injury. Types of violation were not related to
      mode of injury. Although there was a positive association between prior impaired
      driving convictions, current alcohol dependence, and a BAC + status, a consistent
      pattern relative to other violations, PSUDs, and BAC status was not apparent.
      Risk-taking disposition scale scores indicated that patients without PSUDs and
      without convictions tended toward less risk-taking behavior than patients with
      PSUDs and with convictions. The complex inter-relationships between PSUDs, risk
      taking dispositions, and being convicted of driving dangerously require
      additional study so that intervention programs and injury prevention initiatives
      can be targeted effectively.

PMID- 11579980
TI  - Costs of alcohol-related crashes: New Zealand estimates and suggested measures
      for use internationally.
AB  - This paper presents policy-oriented measures of alcohol-related crash incidence
      and costs in New Zealand (N.Z.). Costs of crashes, where alcohol probably was a
      contributing factor were computed from official crash costs and police-reported
      crash/injury counts adjusted for under-reporting of crashes and of alcohol
      involvement. Alcohol-related crashes cost an estimated $1.2 billion in N.Z. in
      1996. They equate to an estimated $0.75 per drink consumed, $17.80 per km driven
      above the legal limit of 0.08. and $1,100 per heavy drinker. People other than
      the drinkers, who caused the crashes, paid half the costs. An estimated one in 90
      drunk-driving trips resulted in a crash (and often a drunk driving conviction)
      while one in 375 crash-free drunk driving trips also resulted in a drunk-driving
      conviction. Ten measures of alcohol-related crash incidence and costs are
      recommended for international use. They include number of alcohol-related deaths
      and injuries; innocent victims and children harmed in crashes caused by drinkers;
      annual costs and costs paid by people other than the drinker who caused the
      crash; crash costs per drink consumed, per heavy drinker, per kilometer driven
      drunk versus sober; probabilities of crash and of drunk-driving conviction.

PMID- 11579981
TI  - Long-term effects of legislation and local promotion of child restraint use in
      motor vehicles in Sweden.
AB  - The main objective is to study long-term effects of legislation and promotion of
      child-restraint use in motor vehicles. Subgoals are to describe the level of
      restraint use in cars and changes in mortality and morbidity patterns in regard
      to differences among age groups and geographical areas (morbidity). The study
      areas were; 'The First Four', 'The Six Counties', 'The Rest of Sweden', and
      'Sweden as a whole', and the population were two age groups--0-6 and 7-14 years.
      The incidence of restraint use comes from observations of car-seat-belt usage.
      Outcome evaluation was based on hospital-discharge data 1978-1996 and mortality
      statistics 1970-1996. The level of restraint use for children in the front seat
      was 97% in 1988 and was equal to 1995. Mortality data shows a decrease of 2.8% on
      an average per year, 76% over the study period. A significant change over time in
      the two intervention areas was shown (annual changes of -2.8 and -1.8%), but not
      in the rest of Sweden. The local authorities that started early with preventive
      programs, such as safety seat loan schemes and those having an organised safety
      promotion program showed a much better improvement than the rest of Sweden. There
      is a need for appropriate information for local action on childhood injury
      prevention to accompany national legislation.

PMID- 11579982
TI  - Overdispersion in modelling accidents on road sections and in empirical bayes
      estimation.
AB  - In multivariate statistical models of road safety one usually finds that the
      accident counts are 'overdispersed'. The extent of the overdispersion is itself
      subject to estimation. It is shown that the assumption one makes about the nature
      of overdispersion will affect the maximum likelihood estimates of model
      parameters. If one assumes that the same overdispersion parameter applies to all
      road sections in the data base, then, the maximum likelihood estimate of
      parameters will be unduly influenced by very short road sections and
      insufficiently influenced by long road sections. The same assumption about the
      overdispersion parameter also leads to an inconsistency when one estimates the
      safety of a road section by the Empirical Bayes method. A way to avoid both
      problems is to estimate an overdispersion parameter (phi) that applies to a unit
      length of road, and to set the overdispersion parameter for a road section of
      length L to phiL. How this would change the estimates of regression parameters
      for road section models now in use requires examination. Safety estimation by the
      Empirical Bayes method is altered substantially.

PMID- 11579983
TI  - Predicting at-fault car accidents of older drivers.
AB  - Considerable research shows car accidents are difficult to predict using
      screening tests. The objective of this exploratory study is to determine whether
      detailed accident analysis taking into account the specific accident type might
      enhance the predictive power of a standardised road test and a set of selected
      neuropsychological tests. Moreover, this study addresses the validity and
      reliability of performance-based driving evaluation. The sample consisted of 84
      older drivers between 65 and 96 years of age who were referred for a fitness-to
      drive evaluation. Using discriminant analyses, the subjects were classified as
      drivers with and without at-fault accidents. We compared the accuracy of
      neuropsychological tests and a road test for postdicting all accidents, accidents
      classified into two categories and accidents classified into four different
      categories. The percentages of correctly classified subject were highest at the
      level of the most detailed classification. These results suggest that, although
      accident prediction is difficult, the predictability of car accidents by
      neurocognitive measurements and a road test increases when the kind of accident
      is specified.

PMID- 11579984
TI  - Predicting ambulatory function following lower extremity trauma using the
      functional capacity index.
AB  - This study evaluated the accuracy of experts' predictions of ambulatory function
      following lower extremity trauma using the Functional capacity index (FCI). Data
      from three orthopedic trauma studies designed to determine long-term function
      following specific types of lower extremity injuries were used to examine the
      extent of agreement between the reported and predicted ambulatory function of 921
      subjects. Functional limitations reported by the cohort using a generalized
      health status measure and more detailed questions on lower extremity function
      were compared with those predicted by experts based on the injuries sustained.
      The overall agreement between predicted and self-reported FCI function for
      ambulation was relatively low (31%). In the majority of cases (80%), the
      disagreement differed by one functional level. Subjects were more likely to
      report worse function than predicted by the experts. Multivariate modeling
      identified different injuries, combinations of injuries, and patient
      characteristics that significantly influenced agreement. For example, subjects
      who sustained both a tibia and a femur fracture were three times more likely than
      subjects who did not sustain either fracture type to report poorer ambulatory
      function than predicted. Many challenges are faced in predicting long-term
      function following trauma. More empirical data are needed to inform the process.
      These data suggest that until the FCI can more accurately predict long-term
      ambulatory function following different lower extremity injuries, it should not
      be used for this purpose.

PMID- 11579985
TI  - Effect of distraction and coping style on in vivo exposure for specific phobia of
      spiders.
AB  - Recent studies have generated mixed findings regarding the effects of distraction
      on exposure-based treatments. Results have also been inconsistent regarding the
      effects of monitoring and blunting coping styles on outcome. The present study
      attempted to integrate these two areas of research. We hypothesized that the
      effect of distraction on treatment outcome might depend on coping style.
      Specifically, we predicted that for blunters (i.e.. individuals who tend to avoid
      threat-related information), distraction would interfere with the effects of
      exposure. However, we predicted that distraction might benefit monitors (i.e.,
      individuals who tend to seek out threat-related information). Sixty individuals
      with a specific phobia of spiders underwent a single, two-hour session of
      exposure treatment. During the first hour, half of the participants were
      distracted by listening to an audiotape and the other half underwent exposure
      without distraction. In the second hour, all participants underwent focused
      exposure. Based on measures of heart rate, subjective fear, and behavioral
      testing, participants improved after one hour of treatment, and improved further
      during the second hour. However, neither distraction, coping style, nor their
      interaction had a significant effect on outcome. The present study provides
      support for the benefits of behavioral treatment for specific phobias. However,
      our hypotheses regarding distraction and coping style were not confirmed.

PMID- 11579986
TI  - Two strategies to increase adherence to HIV antiretroviral medication: life-steps
      and medication monitoring.
AB  - Advances in the medical treatment of HIV have made it clear that adherence to
      highly active antiretroviral treatment is a crucial feature for treatment
      success. The present paper had two goals: (1) to examine psychosocial predictors
      of adherence in persons receiving HIV antiretroviral therapy; (2) to compared two
      minimal-treatment interventions to increase HIV medication adherence in a subset
      of persons who self-reported less than perfect adherence. One of the
      interventions, Life-Steps, is a single-session intervention utilizing cognitive
      behavioral, motivational interviewing, and problem-solving techniques. The other
      intervention, self-monitoring, utilizes a pill-diary and an adherence
      questionnaire alone. Significant correlates of adherence included depression,
      social support, adherence self-efficacy, and punishment beliefs about HIV.
      Depression was a significant unique predictor of adherence over and above the
      other variables. Both interventions yielded improvement in adherence from
      baseline, and the Life-Steps intervention showed faster improvements in adherence
      for persons with extant adherence problems.

PMID- 11579987
TI  - Suppression of obsession-like thoughts in nonclinical individuals: impact on
      thought frequency, appraisal and mood state.
AB  - Wegner's (1994, Psychological Review, 101, 34-52) research on the paradoxical
      effect of thought suppression has been incorporated into contemporary cognitive
      behavioural models of obsessive-compulsive disorder. However, findings on the
      effects of thought suppression on thought frequency have been inconsistent and
      few studies have actually examined the suppression of thoughts that are
      obsessional in nature. In the present study 219 nonclinical participants were
      randomly assigned to suppress or not suppress a neutral, obsessional or positive
      thought during an initial monitoring interval. In a second thought monitoring
      interval, all participants received instructions not to suppress their target
      thought. No paradoxical effect of suppression on frequency was observed for any
      type of thought, although suppression of obsessional thoughts was associated with
      greater subsequent discomfort and a more negative mood state than suppression of
      positive or neutral target thoughts.

PMID- 11579988
TI  - Cognitive-behavior therapy vs exposure therapy in the treatment of PTSD in
      refugees.
AB  - The present study investigated the efficacy of cognitive-behavior therapy (CBT)
      and exposure therapy (E) in the treatment of post-traumatic stress disorder
      (PTSD) in refugees. Sixteen outpatients fulfilling the DSM-IV criteria for PTSD
      were randomized to one of the two treatments. Assessor and self-report measures
      of PTSD-symptoms, generalized anxiety, depression, quality of life and cognitive
      schemas were administered before and after treatment, and at a 6-month follow-up.
      The patients were treated individually for 16-20 weekly sessions. The results
      showed that both treatments resulted in large improvements on all the measures,
      which were maintained at the follow-up. There was no difference between E and CBT
      on any measure. E and CBT led to a 48 and 53% reduction on PTSD-symptoms,
      respectively, a 49 and 50% reduction on generalized anxiety, and a 54 and 57%
      reduction on depression. The results were maintained at the 6-month follow-up.
      The conclusion that can be drawn is that both E and CBT can be effective
      treatments for PTSD in refugees.

PMID- 11579989
TI  - The use of stimulus dimensions in judgement making in spider fearful and
      nonfearful individuals.
AB  - This study uses a multidimensional scaling approach to investigate the hypothesis
      that spider fearful individuals give priority to a threat-safety dimension when
      making judgments. The results show that when making judgments about stimuli,
      spider fearful individuals (1) placed significantly greater comparative weighting
      on a threat-relevant dimension than on a non-emotive dimension (colour), and (2)
      tended to rate threatening pairs of stimuli and safe pairs of stimuli as more
      similar than did the nonfearful group. This prioritised dimensional processing
      suggests a mechanism by which phobics can exhibit what initially appear to be
      paradoxical tendencies to give priority to both threat and safety information.

PMID- 11579990
TI  - Dysfunctional beliefs discriminate personality disorders.
AB  - This study examines whether specific sets of dysfunctional beliefs are
      differentially associated with five personality disorders (PDs) as predicted by
      cognitive theory. Seven hundred fifty-six psychiatric outpatients completed the
      Personality Belief Questionnaire (PBQ) at intake and were assessed for PDs using
      a standardized clinical interview conducted by assessors who were blind to
      patients' PBQ responses. Findings showed that patients with avoidant, dependent,
      obsessive-compulsive, narcissistic, and paranoid PDs preferentially endorsed PBQ
      beliefs theoretically linked to their specific disorders. The study results
      support the cognitive theory of personality disorders. Suggestions are made
      regarding the clinical utility of the PBQ with personality-disordered patients
      and future research on the PBQ.

PMID- 11579991
TI  - Changes in waiting-list patients over time: data on some commonly-used measures.
      Beware!
AB  - When samples of psychiatric patients are assessed on 2 occasions on state and
      trait measures, without any formal intervention having yet taken place, a mean
      change in scores towards less psychopathology is often observed. This re-test
      effect, which is a potential threat to the validity of longitudinal studies, has
      not been given serious attention by researchers using repeated administrations.
      The present study addressed this issue by examining re-test effects in 2
      independent clinical samples with the Symptom Check List-90-Revised and other
      widely-used state and trait measures. Time intervals between intake and re-take
      were 3 months and 11-350 days (M = 93 days, median = 81 days). Results indicated
      that the re-test effect occurred for most of the measures. Where significant
      testing effects were observed, 54-72% of the patients had time 2 scores that were
      lower than the average time I scores. The importance and practical and scientific
      implications of the findings are discussed. Eleven hypotheses concerning the
      nature of the re-test effect are offered, including mood-congruent associative
      processing, natural coping mechanisms, self-monitoring hypothesis and response
      shift.

PMID- 11579992
TI  - Worry: daily self-report in clinical and non-clinical populations.
AB  - The present study establishes an ecologically-valid point of reference for
      generalized anxiety disorder (GAD) treatment outcome studies. Although worry is
      the main diagnostic criterion for GAD, it is also a common and everyday
      cognition. Few studies have investigated the normal manifestation of worry in a
      non-clinical population. For this research, time spent worrying and the tendency
      to worry were measured in a non-clinical sample (n = 36), where GAD was screened
      out, and results were compared to those obtained from a GAD sample (n = 60).
      Participants recorded the time spent worrying in self-monitoring notebooks for
      two consecutive weeks and completed the French version of the Penn State Worry
      Questionnaire (PSWQ). It was found that the non-GAD group reported less time
      spent worrying on a daily basis as well as a lower tendency to worry than the GAD
      group. Results are discussed in terms of treatment implications.

PMID- 11579993
TI  - Effect of a pharmacological activation of PPAR on the expression of RAR and TR in
      rat liver.
AB  - It has recently been shown that high-fat diets induce the expression of
      peroxisome proliferator-activated receptor (PPAR) with a concomitant decrease in
      expression of retinoic acid (RAR) and triiodothyronine (TR) receptors in rat
      liver. The authors have suggested that PPAR activation may be responsible for
      these modifications in nuclear receptor expression. With the aim of gaining
      further insight into a possible relationship between the patterns of expression
      of these receptors, we have examined, using a pharmacological model, the effect
      of a strong and specific PPAR activation induced by bezafibrate, a peroxisome
      proliferator agent. Activation of PPAR was evaluated by quantifying PPARalpha
      mRNA and acyl-CoA oxidase mRNA. The expression of RAR and TR was determined by
      assaying the binding properties of these nuclear receptors and by quantifying the
      mRNA level of RARbeta and TRalpha1,beta1 isoforms. After a 10 day treatment of
      young rats, induction of PPAR (PPARalpha mRNA was increased by 40% [P < 0.05 and
      acyl-CoA oxidase mRNA by 411% [P<0.001]) and a concomitant decrease of RAR and TR
      expression (Maximal Binding Capacity was decreased by 21 and 26%, respectively
      [P<0.05]) in the liver was observed. RXRalpha mRNA expression was unchanged by
      treatment. Cross-talk between RAR, TR and PPAR signalling pathways may be
      implicated in the new patterns of nuclear receptor expression observed. The
      decreased expression of RAR and TR reported here could provide a novel element
      for the understanding of the link between PPAR and tumorigenesis in rat liver.

PMID- 11579994
TI  - Influence of epidermal growth factor on mammalian oocyte maturation via tyrosine
      kinase pathway.
AB  - Epidermal growth factor (EGF) has been reported to promote different functions in
      mammalian ovaries, including oocyte maturation. The aim of the present study was
      to establish: that EGF influences oocyte maturation in ovine and equine, that a
      tyrosine kinase-dependent intracellular mechanism mediates EGF effect and, that
      EGF-R receptor is detectable in ovarian follicles by immunohistochemistry
      methods. Selected ovine and equine oocytes were aspirated from 2-5 mm (ovine) or
      25 mm (equine) follicles and cultured in TCM 199 for 22 (ovine) or 36 hours
      (equine). They are then subjected to culture with EGF and two specific tyrosine
      kinase inhibitors (TKIs, tyrphostins A-23 y A-47). Maturation was determined as
      the percentage of oocytes at metaphase II stage after culture. Treatments with
      EGF significantly increased incidences of metaphase II stage compared to controls
      (86.2% vs. 55% and 70.4% vs. 22.5% in ovine and equine oocytes, respectively).
      Tyrphostins A-23 and A-47 were effective in suppressing EGF-effect on oocytes.
      EGF-receptor was localized in follicles, being more prominent in cumulus and
      granulosa cells. These results confirm that EGF has a physiological role in the
      regulation of oocyte maturation via tyrosine-kinase pathway.

PMID- 11579995
TI  - Endocrine profiles during doe-litter separation and the subsequent pregnancy in
      rabbits.
AB  - This study was carried out to determine the effects of a transient doe-litter
      separation on plasma prolactin, LH, FSH, estradiol-17beta and progesterone
      concentrations before artificial insemination and during the subsequent
      pregnancy. Control does (n=12) had free access to nursing, whereas separated does
      (n=12) were kept away from their litters for 48 hours before artificial
      insemination. Both groups were inseminated on day 11 after parturition. Teat
      stimulation by suckling caused a high increase in prolactin concentrations in
      separated does (p < 0.0001). Basal prolactin concentrations were observed in both
      groups on days 8 and 18 of pregnancy. No effect of the treatment was detected on
      LH and FSH concentrations during the sampling period. A rise of estradiol-17beta
      concentrations was observed 48 hours after doe-litter separation, compared to
      control does and to previous values (p < 0.003). Both groups showed low
      progesterone concentrations before artificial insemination. Pregnant rabbits in
      both groups showed increased progesterone concentrations on days 8 and 18 of
      pregnancy. Lower estradiol-17beta concentrations were observed in control does on
      day 18 of pregnancy compared with separated rabbits (p < 0.003). The results
      suggest that a transient separation of nursing does from their litters before
      artificial insemination may promote high follicular steroidogenesis activity
      leading to increased estradiol-17beta concentrations. This hormonal change could
      be a result of several stimulatory actions probably triggered by the absence of
      suckling episodes and may affect the luteotrophic function during the subsequent
      pregnancy.

PMID- 11579996
TI  - Characterization of a new plasma membrane-associated ecto-5'
      phosphodiesterase/nucleotide-pyrophosphatase from rat hepatocarcinoma AS-30D
      cells.
AB  - We have identified in plasma membrane fractions isolated from rat hepatocarcinoma
      AS-30D ascites cells three glycoproteins of 125 kDa, 115 kDa and 105 kDa (gp125,
      gp115 and gp105) which become adenylylated using ATP as substrate, most readily
      in the presence of EDTA. The gp115 becomes also phosphorylated. The adenylylation
      of these tumor glycoproteins was much lower than that of a group of analogous
      adenylylatable glycoproteins (gp130, gp120-gp110 dimer and gp100) present in
      normal rat liver plasma membrane. The tumor glycoproteins were reversibly O
      adenylylated at threonine residues, as was the case for their normal rat liver
      counterparts. The tumor gp115, and the gp120-gp110 dimer from normal rat liver
      were both isolated using either ATP-affinity chromatography and/or AMP-affinity
      chromatography. The gp120-gp110 dimer from normal rat liver was identified as the
      plasma cell differentiation antigen-1 (PC-1 protein), an ecto-5'
      phosphodiesterase/ nucleotide-pyrophosphatase (5'-PDE/NPPase). The gp115 from
      tumor cells also exhibited Zn2+-stimulated 5'-PDE and NPPase activities in
      alkaline conditions, although it appears to be distinct from the PC-1 protein. We
      have determined that the gp115 is an ecto-enzyme that catalyzes the hydrolysis of
      extracellular ATP, since its adenylylation and phosphorylation were detected in
      intact cells using extracellularly added [alpha-32P]ATP or [gamma-32P]ATP,
      respectively, in the absence of any permeabilizing agent.

PMID- 11579997
TI  - Vitamin E: action, metabolism and perspectives.
AB  - Natural vitamin E includes four tocopherols and four tocotrienols. RRR-alpha
      tocopherol is the most abundant form in nature and has the highest biological
      activity. Although vitamin E is the main lipid-soluble antioxidant in the body,
      not all its properties can be assigned to this action. As antioxidant, vitamin E
      acts in cell membranes where prevents the propagation of free radical reactions,
      although it has been also shown to have pro-oxidant activity. Non-radical
      oxidation products are formed by the reaction between alpha-tocopheryl radical
      and other free radicals, which are conjugated to glucuronic acid and excreted
      through the bile or urine. Vitamin E is transported in plasma lipoproteins. After
      its intestinal absorption vitamin E is packaged into chylomicrons, which along
      the lymphatic pathway are secreted into the systemic circulation. By the action
      of lipoprotein lipase (LPL), part of the tocopherols transported in chylomicrons
      are taken up by extrahepatic tissues, and the remnant chylomicrons transport the
      remaining tocopherols to the liver. Here, by the action of the "alpha-tocopherol
      transfer protein", a major proportion of alpha-tocopherol is incorporated into
      nascent very low density lipoproteins (VLDL), whereas the excess of alpha
      tocopherol plus the other forms of vitamin E are excreted in bile. Once secreted
      into the circulation, VLDL are converted into IDL and LDL by the action of LPL,
      and the excess of surface components, including alpha-tocopherol, are transferred
      to HDL. Besides the LPL action, the delivery of alpha-tocopherol to tissues takes
      place by the uptake of lipoproteins by different tissues throughout their
      corresponding receptors. Although we have already a substantial information on
      the action, effects and metabolism of vitamin E, there are still several
      questions open. The most intriguing is its interaction with other antioxidants
      that may explain how foods containing small amounts of vitamin E provide greater
      benefits than larger doses of vitamin E alone.

PMID- 11579998
TI  - IGF-I does not improve fat malabsorption in cirrhotic rats.

PMID- 11579999
TI  - Physical exercise intensity can be related to plasma glutathione levels.
AB  - The aim of the present study was to examine the effect of different kinds of
      physical exercise on plasma glutathione levels. Male Wistar rats were randomly
      divided into four groups: In walking group (W; n=6), rats were trained to walk
      0.8 m/min for 45 min; slow running group (SR; n=6) were trained to run 4 m/min
      for 45 min; fast running group (FR; n=6) ran 8m/min for 60 min and control rats
      (C; n=6) remained in their home cages. All animals were sacrificed after exercise
      and the levels of reduced glutathione (GSH) in plasma samples determined by high
      performance liquid chromatography (HPLC) with a fluorescent detector. Compared to
      controls, exercise did not change GSH plasma levels of the W group. A tendency to
      decrease blood GSH was observed in plasma samples of the SR group and in the FR
      group, physical exercise resulted in a dramatic decrease in GSH plasma levels.
      These data suggest that during light physical exercise there is a low production
      of reactive oxygen species (ROS) with a low request for antioxidant defence such
      as oxidation of GSH. The dramatic decrease observed in GSH levels in FR rats
      would indicate the presence of oxidative stress able to modify blood antioxidant
      profiles. Our results suggest that GSH plays a central antioxidant role in blood
      during intensive physical exercise and that its modifications are closely related
      to exercise intensity.

PMID- 11580000
TI  - The course of postpartum psychiatric disorders in women and their partners.
AB  - This study examined the course of postpartum psychiatric disorders in a community
      sample of mothers and their partners to determine whether sociodemographic
      variables, life stress, and psychiatric history were related to persistence of
      mental health problems. At 6 months postpartum, 48 index couples where the wife
      had a psychiatric disorder at 2 months postpartum and 50 control couples with no
      such diagnosis underwent diagnostic interviews and completed questionnaires on
      psychological symptoms, life stress, and treatment history. The results indicate
      that at follow-up, 54% of the index mothers still had a psychiatric diagnosis, as
      did 60% of their partners who had had a psychiatric diagnosis at 2 months
      postpartum. Socioeconomic status, country of origin, and life stress were related
      to persistence, as were diagnosis and timing of onset of the disorder. About a
      third of the parents were referred for treatment. It is concluded that for many
      families, postpartum psychiatric disorders are not a transient phenomenon.

PMID- 11580001
TI  - Effects of involuntary outpatient commitment and depot antipsychotics on
      treatment adherence in persons with severe mental illness.
AB  - This study examines potential improvement in treatment adherence during a study
      of involuntary outpatient commitment among individuals with severe mental
      illnesses. Involuntarily hospitalized subjects, awaiting discharge under
      outpatient commitment, were randomly assigned to be released or continue under
      outpatient commitment after hospital discharge. A nonrandomized group with a
      recent history of serious violence was also studied under outpatient commitment.
      Randomized control and outpatient commitment groups did not differ significantly
      in group comparisons of treatment adherence. However, analyses of all subjects,
      including nonrandomized violent subjects, showed that those who underwent
      sustained periods of outpatient commitment (6 months or more) were significantly
      more likely to remain adherent with medication and other treatment, compared with
      those who underwent only brief outpatient commitment or none. Administration of
      depot antipsychotics also significantly improved treatment adherence
      independently of the effect of sustained outpatient commitment. Sustained periods
      of outpatient commitment may significantly improve adherence with community-based
      mental health treatment for persons with severe mental illness and thus may help
      improve other clinical outcomes affected by adherence.

PMID- 11580002
TI  - Influence of antisocial personality subtypes on drug abuse treatment response.
AB  - This methodological study examined the impact of antisocial personality disorder
      (APD) and other psychiatric comorbidity on drug use and treatment retention in
      513 new admissions to methadone maintenance treatment. Patients were classified
      into one of four groups: APD ONLY, APD plus other psychiatric disorder (APD
      MIXED), other psychiatric disorder, and no psychiatric disorder. Patients
      completed research assessments and were then followed for 1 year of treatment.
      Patients with APD had longer histories of heroin and cocaine use than non-APD
      patients and were more likely to meet criteria for cocaine dependence. Distinct
      clinical profiles emerged that differentiated APD ONLY from APD MIXED. APD ONLY
      patients exhibited higher rates of cocaine and heroin use, whereas those with APD
      MIXED exhibited higher rates of benzodiazepine use. Self-report measures
      supported urinalysis results, but group differences did not affect treatment
      retention. These differences in clinical profiles should be considered when
      evaluating treatment performance in substance abusers with APD.

PMID- 11580003
TI  - Relationship between dissociative symptomatology and declarative and procedural
      memory in adolescent psychiatric patients.
AB  - The purpose of this study was to examine the relationship between dissociative
      symptomatology and declarative and procedural memory. Subjects were 41
      consecutively admitted adolescent psychiatric patients, 13 to 19 years old. Each
      subject completed the Adolescent Dissociative Experiences Scale (A-DES).
      Declarative memory was assessed by the California Verbal Learning Test and
      procedural memory by the Tower of Toronto puzzle. All subjects were controlled
      for IQ and severity of psychiatric illness. Data analysis was done by multiple
      regression. Multiple regression analysis revealed a model in which 71% variance
      of the A-DES scores was explained by psychiatric illness and specific memory
      variables. This study confirms a strong interrelationship between clinical
      dissociation and severity of psychiatric illness. Moreover, clinical dissociation
      seems to be associated with specific memory dysfunctions, indicating that
      dissociation exerts an impact on basic information processing.

PMID- 11580004
TI  - Summer birth and deficit schizophrenia in the epidemiological catchment area
      study.
AB  - Winter birth is a widely replicated risk factor for schizophrenia. However,
      previous studies have suggested that patients with the deficit syndrome of
      schizophrenia have an excess of summer births. We tested the summer birth effect
      in a population-based study. Data came from the Epidemiological Catchment Area
      study, which had a representative sample of the U.S. population. Psychotic
      patients with features of the deficit syndrome had a significant association with
      summer birth, compared with the general population. There was also a significant
      association between summer birth and the deficit syndrome within the psychotic
      population, after accounting for the variance due to disorganization,
      hallucinations and delusions, and demographic characteristics. These findings add
      to the evidence suggesting the etiopathophysiology of the deficit group differs
      from that found in other patients with schizophrenia.

PMID- 11580005
TI  - Summer birth and deficit schizophrenia in Nithsdale, Scotland.
AB  - Patients with deficit schizophrenia differ from other people with schizophrenia
      relative to course of illness, treatment response, and neurobiological
      correlates. An association between deficit schizophrenia and summer birth, in
      contrast to the winter birth risk factor associated with schizophrenia as a
      whole, has also been reported. We attempted to replicate the association between
      summer birth and deficit schizophrenia by using data from a prevalence survey in
      Nithsdale in southwest Scotland, in which all patients with schizophrenia in
      Nithsdale were identified and 87% were interviewed directly. Deficit
      schizophrenia was associated with summer birth, defined as birth in
      June/July/August (p < .02), June/July (p < .02), or July/August (p < .03). The
      association with summer birth is consistent with other evidence that patients
      with deficit schizophrenia have a pathophysiology that differs in some ways from
      that of other patients with schizophrenia.

PMID- 11580006
TI  - Trauma-related sleep disturbance and self-reported physical health symptoms in
      treatment-seeking female rape victims.
AB  - The purpose of the study was to assess the relationship between trauma-related
      sleep disturbance and physical health symptoms in treatment-seeking female rape
      victims. A total of 167 participants were assessed for PTSD symptoms, depression,
      sleep disturbance, and frequency of self-reported health symptoms. Results
      demonstrated that trauma-related sleep disturbance predicted unique variance in
      physical health symptoms after other PTSD and depression symptoms were
      controlled. The findings suggest that trauma-related sleep disturbance is one
      potential factor contributing to physical health symptoms in rape victims with
      PTSD.

PMID- 11580007
TI  - Suicidal ideation among patients during the rehabilitation period after life
      threatening physical illness.
AB  - A total of 496 patients were examined for suicidal ideation during the acute
      hospital period and at 3, 6, 12, and 24 months' follow-up after suffering either
      stroke, traumatic brain injury, myocardial infarction, or spinal cord injury. A
      total of 7.3% of patients had suicidal ideation during the in-hospital evaluation
      (acute-onset suicidal ideation), and 11.3% developed it during the chronic 3 to
      24 month rehabilitation period (delayed-onset suicidal ideation). Compared with
      delayed-onset suicidal patients, acute-onset suicidal patients had more
      predisposing risk factors (i.e., personal psychiatric history and alcohol
      abuse/dependence) and less social support (i.e., lower frequency of being
      married). Both acute and delayed-onset suicidal ideation, however, were strongly
      associated with the existence of major depression and impaired social
      functioning. These findings suggest that the detection and appropriate treatment
      of depressive disorders and social isolation may be the most important factor in
      preventing suicide both during the acute and chronic period following life
      threatening physical illnesses.

PMID- 11580008
TI  - The phenomenological stability of depersonalization: comparing the old with the
      new.
AB  - The view that depersonalization is a stable syndrome became well established
      during the first half of the 20th century. Current operational definitions
      restrict depersonalization to the experience of unreality. This is likely to
      neglect clinical features of potential neurobiological relevance. By using the
      year 1946 as the dividing line, 200 cases of depersonalization disorder reported
      in the medical literature since 1898 were divided into two historical groups (1
      and 2). The groups were then compared in terms of 18 phenomenological variables
      with a sample of 45 prospective cases of DSM-IV depersonalization disorder (group
      3 or gold standard). Groups 1 and 2 differed in terms of their symptom profile,
      but the highest frequency that symptoms achieved in either group did not differ
      from the rates identified in group 3. A core of (invariable) symptoms, including
      emotional numbing, visual derealization, and altered body experience, was present
      throughout. These high rates of spontaneous reporting in all three groups may be
      explained by the fact that they all are accompanied by specific distress. With
      the exception of heightened self-observation and altered time experiencing, all
      other symptoms were significantly lower in group 2. The results suggest that the
      phenomenology of depersonalization has remained stable over the last 100 years.
      Our study found differences in frequency for some symptoms, but these are likely
      to have resulted from reporting biases, themselves governed by changing
      theoretical views. Clinical descriptions became poorer as the present is
      approached. This cannot be solely explained on the basis of empirical progress,
      and it is likely that theoretical biases also play a role. Because the
      neurobiological relevance of the symptoms of depersonalization remains unknown,
      it makes sense to continue collecting as many symptoms as possible, thereby
      avoiding both biased selection or premature closure.

PMID- 11580009
TI  - Convergent validity and neuropsychological correlates of the schedule for the
      assessment of negative symptoms (SANS) attention subscale.
AB  - Cognitive deficits have come to be viewed as a hallmark feature of schizophrenic
      illness. Although laboratory based assessment of patients' cognitive deficits has
      been well investigated, few studies to date have examined the utility of clinical
      ratings of cognitive symptoms using the Schedule for the Assessment of Negative
      Symptoms (SANS) attention subscale. In this report, we examined the convergence
      between clinical ratings of cognitive impairment using the SANS attention
      subscale and performance on a variety of neurocognitive tests designed to measure
      attentional impairment, as well as other cognitive constructs such as working
      memory and executive functioning. A total of 56 acute schizophrenic inpatients
      were clinically rated with the SANS and completed the Continuous Performance
      Test, Digit Span Distraction Test, Wisconsin Card Sorting Task, and the
      Trailmaking Test. A series of correlational and regression analyses were
      conducted to test the concurrent and discriminant validity of the SANS attention
      subscale. Performance measures of attention, but not working memory or executive
      functioning, were significantly correlated with and moderately predicted the
      severity of SANS rated inattention. Additionally, the attention subscale was
      discriminated from the other SANS negative symptom subscales in predicting a
      laboratory measure of attentional functioning. The SANS attention subscale
      demonstrated both concurrent and discriminant validity. These data indicate that
      attentional dysfunction in schizophrenia can be meaningfully rated and
      interpreted using the SANS.

PMID- 11580010
TI  - Seasonal admission patterns in first episode psychosis, chronic schizophrenia,
      and nonschizophrenic psychoses.

PMID- 11580011
TI  - Reconnecting cell and animal lineages: what do cell lineages tell us about the
      evolution and development of Spiralia?
AB  - Cell lineage studies in the clade Eutrochozoa, and especially the Spiralia,
      remains a rich and relatively untapped source for understanding broad
      evolutionary developmental problems; including (1) the utility of cell timing
      formation for phylogenetic hypotheses; (2) the evolution of cell timing changes
      and its relation to heterochronic patterns; (3) stereotypy or lack thereof in
      rates of change of cell growth during evolution and its relation to both
      evolutionary history and current usage; and (4) how mosaic cleavage timing
      variation may be expected to differ from other groups. A compilation of available
      cell timing information was made from previous studies where each division was
      explicitly followed and the total number of cells followed was greater than 24.
      From that compilation, we performed a series of heuristic and quantitative
      analyses, including a phylogenetic analysis using cell timing data as characters
      and analyses of timing variation across all taxa. Our results show that: (1) cell
      lineage data reconstructs a phylogenetic hypothesis that has similarities,
      especially among the Mollusca. to the patterns found in morphological and
      molecular analyses; (2) the mesentoblast (4d) is a unique cell compared to other
      cell in that it speeds up and slows down relative to other cells in taxa with
      both unequal and equal cell sizes; (3) some cells that form in the same quartet
      at the same point in the cell lineage hierarchy have much lower variations than
      analogous other cells, arguing for architectural constraint or stabilizing
      selection acting on those cells; and (4) although variation in cell timing
      generally increases during development, timing of formation of progeny cells in
      the first quartet has lower variation than the parent cells, arguing that some
      regulation-like behavior might be present.

PMID- 11580012
TI  - When sources become sinks: migrational meltdown in heterogeneous habitats.
AB  - We consider the evolution of ecological specialization in a landscape with two
      discrete habitat types connected by migration, for example, a plant-insect system
      with two plant hosts. Using a quantitative genetic approach. we study the joint
      evolution of a quantitative character determining performance in each habitat
      together with the changes in the population density. We find that specialization
      on a single habitat evolves with intermediate migration rates, whereas a
      generalist species evolves with both very low and very large rates of movement
      between habitats. There is a threshold at which a small increase in the
      connectivity of the two habitats will result in dramatic decrease in the total
      population size and the nearly complete loss of use of one of the two habitats
      through a process of "migrational meltdown." In some situations, equilibria
      corresponding to a specialist and a generalist species are simultaneously stable.
      Analysis of our model also shows cases of hysteresis in which small transient
      changes in the landscape structure or accidental demographic disturbances have
      irreversible effects on the evolution of specialization.

PMID- 11580013
TI  - Consequences of population structure on genes under balancing selection.
AB  - This paper describes a new approach to modeling population structure for genes
      under strong balancing selection of the type seen in plant self-incompatibility
      systems and the major histocompatibility complex (MHC) system of vertebrates.
      Simple analytic solutions for the number of alleles maintained at equilibrium and
      the expected proportion of alleles shared between demes at various levels are
      derived and checked against simulation results. The theory accurately captures
      the dynamics of allele number in a subdivided population and identifies important
      values of m (migration rate) at which allele number and distribution change
      qualitatively. Starting from a panmictic population, as migration among demes
      decreases a qualitative change in dynamics is seen at approximately m(crit)
      approximately equal to the square root of(s/4piNT) where NT is the total
      population size and s is a measure of the strength of selection. At this point,
      demes can no longer maintain their panmictic allele number, due to increasing
      isolation from the total population. Another qualitative change occurs at a
      migration rate on the same order of magnitude as the mutation rate, mu. At this
      point, the demes are highly differentiated for allele complement, and the total
      number of alleles in the population is increased. Because in general u <<
      m<(crit) at intermediate migration rates slightly fewer alleles may be maintained
      in the total population than are maintained at panmixia. Within this range, total
      allele number may not be the best indicator of whether a population is
      effectively panmictic, and some caution should be used when interpreting samples
      from such populations. The theory presented here can help to analyze data from
      genes under balancing selection in subdivided populations.

PMID- 11580014
TI  - Evolution of myrmecophytism in western Malesian Macaranga (Euphorbiaceae).
AB  - Plants inhabited by ants (myrmecophytes) have evolved in a diversity of tropical
      plant lineages. Macaranga includes approximately 300 paleotropical tree species;
      in western Malesia there are 26 myrmecophytic species that vary in morphological
      specializations for ant association. The origin and diversification of
      myrmecophytism in Macaranga was investigated using phylogenetic analyses of
      morphological and nuclear ITS DNA characters and studies of character evolution.
      Despite low ITS variation, the combined analysis resulted in a well-supported
      hypothesis of relationships. Mapping myrmecophytism on all most parsimonious
      trees resulting from the combined analysis indicated that the trait evolved
      independently between two and four times and was lost between one and three times
      (five changes). This hypothesis was robust when tested against trees constrained
      to have three or fewer evolutionary transformations, although increased taxon
      sampling for the ITS analysis is required to confirm this. Mapping morphological
      traits on the phylogeny indicated that myrmecophytism was not homologous among
      lineages; each independent origin involved a suite of different specializations
      for ant-plant association. There was no evidence that myrmecophytic traits
      underwent sequential change through evolution; self-hollowing domatia evolved
      independently from ant-excavated domatia, and different food-body production
      types evolved in different lineages. The multiple origins of myrmecophytism in
      Macaranga were restricted to one small, exclusively western Malesian lineage of
      an otherwise large and nonmyrmecophytic genus. Although the evolution of
      aggregated food-body production and the formation of domatia coincided with the
      evolution of myrmecophytism in all cases, several morphological, ecological, and
      biogeographic factors appear to have facilitated and constrained this radiation
      of ant-plants.

PMID- 11580015
TI  - Spatial population genetic structure in Trillium grandiflorum: the roles of
      dispersal, mating, history, and selection.
AB  - The roles of the various potential ecological and evolutionary causes of spatial
      population genetic structure (SPGS) cannot in general be inferred from the extant
      structure alone. However, a stage-specific analysis can provide clues as to the
      causes of SPGS. We conducted a stage-specific SPGS analysis of a mapped
      population of about 2000 Trillium grandiflorum (Liliaceae), a long-lived
      perennial herb. We compared SPGS for juvenile (J), nonreproductive (NR), and
      reproductive (R) stages. Fisher's exact test showed that genotypes had Hardy
      Weinberg frequencies at all loci and stage classes. Allele frequencies did not
      differ between stages. Bootstrapped 99% confidence intervals (99%CI) indicate
      that F-statistic values are indistinguishable from zero, (except for a slightly
      negative FIT for the R stage). Spatial autocorrelation was used to calculate f
      the average kinship coefficient between individuals within distance intervals.
      Null hypothesis 99%CIs for f were constructed by repeatedly randomizing genotypic
      locations. Significant positive fine-scale genetic structure was detected in the
      R and NR stages, but not in the J stage. This structure was most pronounced in
      the R stage, and declined by about half in each remaining stage: near-neighbor f
      = 0.122, 0.065, 0.027, for R, NR, and J, respectively. For R and NR, the near
      neighbor f lies outside the null hypothesis 99%CI, indicating kinship at
      approximately the level of half-sibs and first cousins, respectively. We also
      simulated the expected SPGS of juveniles post dispersal, based on measured R
      stage SPGS, the mating system, and measured pollen and seed dispersal properties.
      This provides a null hypothesis expectation (as a 99%CI) for the J-stage
      correlogram, against which to test the likelihood that post-dispersal events have
      influenced J-stage SPGS. The actual J correlogram lies within the null hypothesis
      99%CI for the shortest distance interval and nearly all other distance intervals
      indicating that the observed low recruitment, random mating and seed dispersal
      patterns are sufficient to account for the disappearance of SPSG between the R
      and the J stages. The observed increase in SPGS between J and R stages has two
      potential explanations: history and local selection. The observed low total
      allelic diversity is consistent with a past bottleneck: a possible historical
      explanation. Only a longitudinal stage-specific study of SPGS structure can
      distinguish between historical events and local selection as causes of increased
      structure with increasing life history stage.

PMID- 11580016
TI  - Population size and fragmentation thresholds for the maintenance of genetic
      diversity in the herbaceous endemic Scutellaria montana (Lamiaceae).
AB  - Abstract.-The level and distribution of genetic variation is thought to be
      affected primarily by the size of individual populations and by gene flow among
      populations. Although the effects of population size have frequently been
      examined, the contributions of regional gene flow to levels of genetic variation
      are less well known. Here I examine the effects of population size and the number
      of neighboring populations (metapopulation density) on the distribution and
      maintenance of genetic diversity in an endemic herbaceous perennial. Reductions
      in the proportion of polymorphic loci and the effective number of alleles per
      locus were apparent for many populations with a census size of less than 100
      individuals, but no effects of population size on levels of inbreeding were
      detected. I assess the effects of regional population density on levels of
      diversity and inbreeding using stepwise regression analysis of metapopulation
      diameter (i.e., the size of a circle within which population density is
      estimated). This procedure provides a spatially explicit evaluation of the
      effects of metapopulation size on population genetic parameters and indicates the
      critical number of neighboring populations (fragmentation threshold) for the
      regional maintenance of genetic diversity. Stepwise regression analyses revealed
      fragmentation thresholds at two levels; at a scale of 2 km, where small
      metapopulations resulted in greater levels of selfing or sibling mating, and at a
      scale of 8 km, where metapopulation size was positively associated with higher
      levels of genetic diversity. I hypothesize that the smaller fragmentation
      threshold may reflect higher levels of selfing in isolated populations because of
      the absence of pollinators. The larger threshold probably indicates the maximum
      distance over which pollen dispersal rates are high enough to counteract genetic
      drift. This study demonstrates that the regional distribution of populations can
      be an important factor for the long-term maintenance of genetic variation.

PMID- 11580017
TI  - The importance of sexual and asexual reproduction in the recent evolution of
      Allium vineale.
AB  - In the weedy plant species Allium vineale (wild garlic), individuals may
      simultaneously produce sexually and asexually derived offspring, by seed and
      bulbils, respectively. In this study, genetic and genotypic diversity was
      determined in samples from 14 European A. vineale populations using nuclear
      (RAPD) and cytoplasmic (PCR-RFLP of cpDNA) markers to investigate the importance
      of the different reproductive modes. In the whole sample, 77 nuclear multilocus
      genotypes and four chloroplast haplotypes (chlorotypes) were found. Populations
      exhibited a high degree of subdivision for nuclear and cytoplasmic markers as
      estimated from hierarchical F-statistics; at the same time, identical chlorotypes
      could be found in populations separated by large distances. Genotypic diversity
      was significantly lower than expected under free recombination in almost all
      populations, indicating that recruitment into populations is mostly by asexually
      produced offspring. Nevertheless, within each chlorotype, the distribution of
      markers from pairs of nuclear loci was incompatible with a purely clonal
      structure, suggesting that many multilocus genotypes have originated by sexual
      recombination rather than by mutation within asexual lineages. It is argued that
      the weedy habit of A. vineale is likely to have favored bulbil reproduction,
      whereas sexually generated genotypes may have facilitated local adaptation during
      the species' expansion across Europe.

PMID- 11580018
TI  - Viability of cytochrome c genotypes depends on cytoplasmic backgrounds in
      Tigriopus californicus.
AB  - Because of their extensive functional interaction, mitochondrial DNA (mtDNA) and
      nuclear genes may evolve to form coadapted complexes within reproductively
      isolated populations. As a consequence of coadaptation, the fitness of particular
      nuclear alleles may depend on mtDNA genotype. Among populations of the copepod
      Tigriopus californicus, there are high levels of amino acid substitutions in both
      the mtDNA genes encoding subunits of cytochrome c oxidase (COX) and the nuclear
      gene encoding cytochrome c (CYC), the substrate for COX. Because of the
      functional interaction between enzyme and substrate proteins, we hypothesized
      that the fitness of CYC genotypes would depend on mtDNA genotype. To test this
      hypothesis, segregation ratios for CYC and a second nuclear marker (histone H1)
      unrelated to mitochondrial function were scored in F2 progeny of several
      reciprocal interpopulation crosses. Genotypic ratios at the CYC locus (but not
      the H1 locus) differed between reciprocal crosses and differed from expected
      Mendelian ratios, suggesting that CYC genotypic fitnesses were strongly
      influenced by cytoplasmic (including mtDNA) background. However, in most cases
      the nature of the deviations from Mendelian ratios and differences between
      reciprocal crosses are not consistent with simple coevolution between CYC and
      mtDNA background. In a cross in which both newly hatched larvae and adults were
      sampled, only the adult sample showed deviations from Mendelian ratios,
      indicating that genotypic viabilities differed. In two of six crosses, large
      genotypic ratio differences for CYC were observed between the sexes. These
      results suggest that significant variation in nuclear-mtDNA coadaptation may
      exist between T. californicus populations and that the relative viability of
      specific cytonuclear allelic combinations is somehow affected by sex.

PMID- 11580019
TI  - A cost of reproduction in Drosophila melanogaster: stress susceptibility.
AB  - Little is known about physiological mechanisms that underlie the cost of
      reproduction. We tested the hypothesis that stress susceptibility is a cost of
      reproduction. In one test of our hypothesis, Drosophila melanogaster females were
      exposed to a juvenile hormone analog (methoprene) to stimulate egg production
      followed by stress assays. A sterile stock of D. melanogaster was employed as a
      control for reproduction. Exposure of fertile females to methoprene resulted in
      an increase in female reproduction and increased susceptibility to oxidative
      stress and starvation (compared to solvent controls). Sterile females did not
      exhibit a decrease in stress resistance. Mating also stimulated egg production.
      As a second test of our hypothesis, mated females were compared to virgin
      females. Mated fertile females were relatively susceptible to oxidative stress,
      but this relationship was not evident when mated and virgin sterile females were
      compared. The results of the present study support the hypothesis that stress
      susceptibility is a cost of reproduction.

PMID- 11580020
TI  - Genetic variation for preadult viability in Drosophila melanogaster.
AB  - The extent of genetic variation in fitness and its components and genetic
      variation's dependence on environmental conditions remain key issues in
      evolutionary biology. We present measurements of genetic variation in preadult
      viability in a laboratory-adapted population of Drosophila melanogaster, made at
      four different densities. By crossing flies heterozygous for a wild-type
      chromosome and one of two different balancers (TM1, TM2), we measure both
      heterozygous (TM1/+, TM2/+) and homozygous (+/+) viability relative to a standard
      genotype (TM1/TM2). Forty wild-type chromosomes were tested, of which 10 were
      chosen to be homozygous viable. The mean numbers produced varied significantly
      between chromosome lines, with an estimated between-line variance in log(e)
      numbers of 0.013. Relative viabilities also varied significantly across
      chromosome lines, with a variance in log(e) homozygous viability of 1.76 and of
      log(e) heterozygous viability of 0.165. The between-line variance for numbers
      emerging increased with density, from 0.009 at lowest density to 0.079 at
      highest. The genetic variance in relative viability increases with density, but
      not significantly. Overall, the effects of different chromosomes on relative
      viability were remarkably consistent across densities and across the two
      heterozygous genotypes (TM1, TM2). The 10 lines that carried homozygous viable
      wild-type chromosomes produced significantly more adults than the 30 lethal lines
      at low density and significantly fewer adults at the highest density. Similarly,
      there was a positive correlation between heterozygous viability and mean numbers
      at low density, but a negative correlation at high density.

PMID- 11580021
TI  - Levels of variation in stress resistance in drosophila among strains, local
      populations, and geographic regions: patterns for desiccation, starvation, cold
      resistance, and associated traits.
AB  - Stress resistance traits in Drosophila often show clinal variation. Although
      these patterns suggest selection, there is generally no attempt to test how large
      differences at the geographical level are relative to levels of variation within
      and between local populations. Here we compare these levels in D. melanogaster
      from temperate Tasmania versus tropical northern Queensland by focusing on adult
      resistance to desiccation, cold and starvation stress, as well as associated
      traits (size, lipid content). For starvation and desiccation resistance, levels
      of variation were highest among strains from the same population. whereas there
      was little differentiation among local populations and a low level of
      differentiation at the geographic level. For adult cold resistance, there was
      local differentiation and strain variation but no geographic variation. For size
      (thorax length), geographic differentiation was higher despite some overlap among
      strains from the tropical and temperate locations. Finally, for lipid levels
      there was only evidence for variation among strains. The low level of
      differentiation among geographic locations for stress resistance was further
      verified with the characterization of isofemale strains from 18 locations along a
      coastal transect extending from Tasmania to northern Queensland. Crosses among
      some of the isofemale strains showed that results were not confounded by
      inbreeding effects. Strains derived from a cross between a tropical and temperate
      strain differed for all traits, and variation among strains for body size was
      higher than strain variation within the geographic regions. Unlike in previous
      studies, lipid content and starvation resistance were not correlated in any set
      of strains, but there was a correlation between cold resistance and lipid
      content. There was also a correlation between desiccation resistance and size but
      only in the geographic cross strains. These findings suggest a large amount of
      variation in stress resistance at the population level and inconsistent
      correlation patterns across experimental approaches.

PMID- 11580022
TI  - Sex-linked hybrid sterility in a butterfly.
AB  - Recent studies, primarily in Drosophila, have greatly advanced our understanding
      of Haldane's rule, the tendency for hybrid sterility or inviability to affect
      primarily the heterogametic sex (Haldane 1922). Although dominance theory
      (Turelli and Orr 1995) has been proposed as a general explanation of Haldane's
      rule, this remains to be tested in female-heterogametic taxa, such as the
      Lepidoptera. Here we describe a novel example of Haldane's rule in Heliconius
      melpomene (Lepidoptera; Nymphalidae). Female F1 offspring are sterile when a male
      from French Guiana is crossed to a female from Panama, but fertile in the
      reciprocal cross. Male F1s are fertile in both directions. Similar female F1
      sterility occurs in crosses between French Guiana and eastern Colombian
      populations. Backcrosses and linkage analysis show that sterility results from an
      interaction between gene(s) on the Z chromosome of the Guiana race with autosomal
      factors in the Panama genome. Large X (or Z) effects are commonly observed in
      Drosophila, but to our knowledge have not been previously demonstrated for hybrid
      sterility in Lepidoptera. Differences in the abundance of male versus female or Z
      linked versus autosomal sterility factors cannot be ruled out in our crosses as
      causes of Haldane's rule. Nonetheless, the demonstration that recessive Z-linked
      loci cause hybrid sterility in a female heterogametic species supports the
      contention that dominance theory provides a general explanation of Haldane's rule
      (Turelli and Orr 2000).

PMID- 11580023
TI  - Unexpected consequences of polyandry for parasitism and fitness in the bumblebee,
      Bombus terrestris.
AB  - Multiple mating by females (polyandry) is taxonomically widespread but the
      evolution of such behaviors is not clearly understood given potential costs of
      polyandry such as time, energy, or predation risk. The genetic variability versus
      parasites hypothesis predicts a reduction of parasitism due to increased genetic
      variability among offspring and an associated fitness gain. We tested this
      hypothesis with a field experiment in the bumblebee, Bombus terrestris L. Worker
      heterogeneity within the colony was experimentally altered by artificially
      inseminating queens with sperm from one male, four brothers, two males, or four
      unrelated males. We found genetic variability to be effective, because intensity
      and prevalence of the most common parasite, Crithidia bombi, a trypanosome,
      decreased with increasing levels of colony heterogeneity. Fitness differed
      between treatments but did not increase in a simple way, with increasing genetic
      heterogeneity among colony workers. Instead, fitness followed a U-shaped function
      with a minimum for small amounts of genetic heterogeneity. We therefore suggest
      that polyandry also induces a cost, perhaps as a result of the social structure
      within the colony. In evolutionary terms, singly mated females appear to be
      constrained by an adaptive valley that needs to be crossed before high degrees of
      mating frequency can be reached. This may help to explain why B. terrestris and
      most other social insects are often monandrous.

PMID- 11580024
TI  - Female guppies agree to differ: phenotypic and genetic variation in mate-choice
      behavior and the consequences for sexual selection.
AB  - Variation among females in mate choice may influence evolution by sexual
      selection. The genetic basis of this variation is of interest because the
      elaboration of mating preferences requires additive genetic variation in these
      traits. Here we measure the repeatability and heritability of two components of
      female choosiness (responsiveness and discrimination) and of female preference
      functions for the multiple ornaments borne by male guppies (Poecilia reticulata).
      We show that there is significant repeatable variation in both components of
      choosiness and in some preference functions but not in others. There appear to be
      several male ornaments that females find uniformly attractive and others for
      which females differ in preference. One consequence is that there is no
      universally attractive male phenotype. Only responsiveness shows significant
      additive genetic variation. Variation in responsiveness appears to mask variation
      in discrimination and some preference functions and may be the most biologically
      relevant source of phenotypic and genetic variation in mate-choice behavior. To
      test the potential evolutionary importance of the phenotypic variation in mate
      choice that we report, we estimated the opportunity for and the intensity of
      sexual selection under models of mate choice that excluded and that incorporated
      individual female variation. We then compared these estimates with estimates
      based on measured mating success. Incorporating individual variation in mate
      choice generally did not predict the outcome of sexual selection any better than
      models that ignored such variation.

PMID- 11580025
TI  - Migratory costs and the evolution of egg size and number in introduced and
      indigenous salmon populations.
AB  - The trade-off between reproductive investment and migration should be an
      important factor shaping the evolution of life-history traits among populations
      following their radiation into habitats with different migratory costs and
      benefits. An experimentally induced difference in migratory rigor for families of
      chinook salmon (Oncorhynchus tshawytscha), of approximately 86 km and 413 m
      elevation, exacted a cost to somatic energy reserves (approximately 17% reduction
      in metabolizable mass) and ovarian investment (13.7% reduction in ovarian mass).
      This cost was associated with a reduction in egg size and paralleled the
      phenotypic pattern of divergence between two introduced New Zealand populations
      of common origin, presently breeding at sites with different migration distances.
      The genetic pattern of divergence of these same populations, detected under
      common rearing, was consistent with compensation for migratory costs (the
      population that migrates farther invested more in ovarian mass), but egg number
      more than egg size was associated with this evolution. These evolutionary
      patterns are consistent with what is known of the inheritance of these traits and
      with trade-offs and constraints favoring initial evolution in offspring number
      over offspring size. Analysis of egg number-size patterns of other Pacific salmon
      populations in their native range supported the hypothesis that migration
      strongly influences patterns of reproductive allocation, favoring a higher ratio
      of egg number to egg size with greater migration distance.

PMID- 11580026
TI  - A quantitative genetic test of adaptive decoupling across metamorphosis for
      locomotor and life-history traits in the pacific tree frog, Hyla regilla.
AB  - Metamorphosis is assumed to be beneficial because it can break developmental
      links between traits in the different phases of a complex life-cycle and thereby
      allow larval and adult phases to adapt independently. I tested the prediction
      that correlations between the larval and adult phases are smaller than within
      stages. I estimated phenotypic and additive genetic variances and correlations
      for tadpole swimming speed, frog jump distance, body size, and larval period in a
      single population of the Pacific tree frog, Hyla regilla. These traits are known
      or reasonably assumed to be important for survival in this and other anuran
      species from temporary ponds. Only the three size variables were affected by sire
      identity. Heritabilities for locomotor performance, larval period, and size
      independent performance were low (0.00-0.23) and not significant. Body size
      measurements showed somewhat higher and statistically significant heritabilities
      (0.24-0.34). Most traits were phenotypically correlated. On average, phenotypic
      correlations were larger between phases than within phases (0.41 vs. 0.28).
      Genetic correlations involving body-size traits were positive and large, and
      average within- and between-phase genetic correlation coefficients were identical
      (0.81). These results do not support the adaptive decoupling hypothesis, and they
      indicate that a paucity of additive genetic variation is a likely constraint on
      the evolution of traits measured for this population.

PMID- 11580027
TI  - Historical population size change of bowhead whales inferred from DNA sequence
      polymorphism data.
AB  - Nucleotide sequence data from the mitochondrial control region were used from a
      phylogenetic context to investigate the long-term history of a population of
      bowhead whales (Balaena mysticetus). In addition, the coalescence time of these
      sequences was used to estimate the age of the inferred patterns of population
      size change. The results indicate that mitochondrial genetic polymorphism was not
      affected by a recent bottleneck that occurred near the turn of the 20th century,
      thereby preserving the signature of historical population size change in the
      mitochondrial genome. Further analysis showed that this population underwent an
      expansion initiated in the Middle to Late Pleistocene. As such, early Holocene
      changes in Arctic sea ice distribution appear to have had little influence on
      patterns of genetic variability in this population.

PMID- 11580028
TI  - Hybridization and population genetics of two macaque species in Sulawesi,
      Indonesia.
AB  - This study investigates hybridization and population genetics of two species of
      macaque monkey in Sulawesi, Indonesia, using molecular markers from
      mitochondrial, autosomal, and Y-chromosome DNA. Hybridization is the
      interbreeding of individuals from different parental taxa that are
      distinguishable by one or more heritable characteristics. Because hybridization
      can affect population structure of the parental taxa, it is an important
      consideration for conservation management. On the Indonesian island of Sulawesi
      an explosive diversification of macaques has occurred; seven of 19 species in the
      genus Macaca live on this island. The contact zone of the subjects of this study,
      M. maura and M. tonkeana, is located at the base of the southwestern peninsula of
      Sulawesi. Land conversion in Sulawesi is occurring at an alarming pace; currently
      two species of Sulawesi macaque, one of which is M. maura, are classified as
      endangered species. Results of this study indicate that hybridization among M.
      maura and M. tonkeana has led to different distributions of molecular variation
      in mitochondrial DNA and nuclear DNA in the contact zone; mitochondrial DNA shows
      a sharp transition from M. maura to M. tonkeana haplotypes, but nuclear DNA from
      the parental taxa is homogenized in a narrow hybrid zone. Similarly, within M.
      maura divergent mitochondrial DNA haplotypes are geographically structured but
      population subdivision in the nuclear genome is low or absent. In M. tonkeana,
      mitochondrial DNA haplotypes are geographically structured and a high level of
      nuclear DNA population subdivision is present in this species. These results are
      largely consistent with a macaque behavioral paradigm of female philopatry and
      obligate male dispersal, suggest that introgression between M. maura and M.
      tonkeana is restricted to the hybrid zone, and delineate one conservation
      management unit in M. maura and at least two in M. tonkeana.

PMID- 11580029
TI  - Are partial mantel tests adequate?
AB  - Partial Mantel tests were designed to test for correlation among three matrices
      of pairwise distances. We show through an example that these tests may be
      inadequate, because the associated P-value is not indicative of the type I error.

PMID- 11580030
TI  - Mimicry on the QT(L): genetics of speciation in Mimulus.
AB  - Ecological studies suggest that hummingbird-pollinated plants in North America
      mimic each other to increase visitation by birds. Published quantitative trait
      locus (QTL) data for two Mimulus species indicate that floral traits associated
      with hummingbird versus bee pollination results from a few loci with major
      effects on morphology, as predicted by classical models for the evolution of
      mimicry. Thus, the architecture of genetic divergence associated with speciation
      may depend on the ecological context.

PMID- 11580031
TI  - Within-species diversity of Wolbachia-induced cytoplasmic incompatibility in
      haplodiploid insects.
AB  - Wolbachia-induced cytoplasmic incompatibility (CI) can have two consequences in
      haplodiploid insects: fertilized eggs either die (female mortality, FM) or they
      develop into haploid males (male development, MD). Origin of this diversity
      remains poorly understood, but current hypotheses invoke variation in damage
      suffered by paternal chromosomes in incompatible eggs, thus intermediate CI types
      should be expected. Here, we show the existence of such a particular CI type. In
      the parasitoid wasp Leptopilina heterotoma, we compared CI effects in crosses
      involving lines derived from a single inbred line with various Wolbachia
      infection statuses (natural tri-infection, mono-infection, or no infection). Tri
      infected males induce a FM CI type when crossed with either uninfected or mono
      infected females. Crossing mono-infected males with uninfected females results in
      almost complete CI with both reduced offspring production, indicating partial
      mortality of fertilized eggs, and increased number of sons, showing haploid male
      development of others. Mono-infected males thus induce an intermediate Cl type
      when mated with uninfected females. The first evidence of this expected
      particular CI type demonstrates that no discontinuity separates MD and FM CI
      types, which appear to be end points of a phenotypic continuum. Second, different
      CI types can occur within a given species and even within offspring of a single
      pair. Third, phenotypic expression of the particular CI type induced by a given
      Wolbachia variant depends on other bacterial variants that co-infect the same
      tissues. These results support the idea that haplodiploids should be helpful in
      clarifying evolutionary pathways of insect-Wolbachia associations.

PMID- 11580032
TI  - Deltamethrin treated bednets for control of malaria transmitted by Anopheles
      culicifacies (Diptera: Culicidae) in India.
AB  - In a malaria endemic area in Orissa state in eastern India baseline (November
      1989 to October 1990) malaria incidence ranged front 215 to 328 cases/1,000
      population/yr in different groups of villages. In November 1990, nylon bednets
      treated with deltamethrin at 25 mg/m2 were given out in two villages (population
      1062), untreated bednets were given out in five villages (population 1,226) and
      in one village (population 786) nets were not given. Nets were retreated in
      October 1991 and June 1992 in treated-net villages. The trial continued until
      October 1992. The treated nets caused significant reduction in indoor resting
      density, biting (landing), light trap catches, human engorgement rate, and parous
      rate of malaria vector Anopheles culicifacies Giles as compared with untreated
      nets or no nets. Untreated nets also caused reductions in biting and indoor
      density. Treated nets retained insecticidal action well over 6 mo. In the final
      year, malaria incidence was reduced 8.9% in the no-net village, 34.9% in the
      villages with untreated nets, and 59.1% in villages with treated nets. The
      relative risk of malaria and parasite rates declined significantly in villages
      with treated nets. Pediatric splenomegaly rate did not change in the no-net
      village, increased significantly in villages with untreated nets, but decreased
      significantly in those with treated nets. Treated nets also reduced pediatric
      anemia rates, but Hb concentration increased in all villages. Considering the
      benefits of treated bednets and development of resistance among vectors to DDT
      and malathion, bednets treated with deltamethrin could be an effective
      alternative strategy to control malaria in forested areas in India.

PMID- 11580033
TI  - Detection of insecticide resistance in Aedes aegypti (Diptera: Culicidae) from
      Cuba and Venezuela.
AB  - Four strains of Aedes aegypti (L.), one from Cuba and three from Venezuela, were
      bioassayed for susceptibility to eight insecticides, including the
      organophosphates, temephos, malathion, fenthion, pirimiphos methyl, and
      chlorpyrifos, and the pyrethroids, deltamethrin, lambda cyhalothrin and
      cypermethrin, S, S, S,-tributyl phosphorotrithioate and piperonyl butoxide were
      used as synergists to assess the involvement of esterases and monooxygenases in
      organophosphate resistance. Venezuelan strains had low levels of resistance to
      fenthion and malathion, and moderate to high resistance to temephos, pyrimphos
      methyl, and chlorpiriphos. All strains were susceptible to the pyrethroids,
      except the Cuban strain, which had moderate levels of resistance to cypermethrin.
      Organophosphate resistance in Ae. aegypti is a serious threat to control
      operations. Integrated strategies for Ae. aegypti control to prevent or delay
      pyrethroid resistance in Venezuela and Cuba are discussed.

PMID- 11580034
TI  - Effect of air temperature and humidity on the survival of pre-imaginal stages of
      two flea species (Siphonaptera: Pulicidae).
AB  - The survival of immatture fleas at 25 and 28 degrees C and 40, 55, 75, and 92% RH
      was studied to test the hypothesis that the difference in microclimatic
      preferences determines habitat distribution of Xenopsylla conformis Wagner, 1903
      and Xenopsylla ramesis Rothschild, 1904. Survival of X. conformis eggs did not
      depend on either temperature or humidity or both, whereas eggs of X. ramesis
      survived significantly less at 40% RH than at higher humidities. No larva of
      either species survived at 40% RH at either temperature. Larval survival of both
      species at both temperature regimes was significantly lower at 55% humidity than
      at higher humidities. Maximal survival time of larvae that died before pupation
      depended on both temperature and humidity in both species. Change of humidity
      during early stages of the life cycle (from egg to larva) increased the maximal
      survival time in X. conformis larvae but decreased that in X. ramesis larvae.
      Pupal survival was higher at higher humidities independent of temperature.
      Survival of X. conformis pupae was lower than that of X. ramesis pupae when the
      relative humidity was low. Humidity change on later stages (from larva to cocoon)
      decreased X. conformis pupal survival and had no effect on X. ramesis pupal
      survival. The sex ratio of emerged adults was not affected by either temperature
      or humidity in both species. Changes in humidity between egg and larval
      emvironments significantly decreased the percentage of females in X. conformis
      emergence at 28 degrees C.

PMID- 11580035
TI  - Sylvatic triatominae of the phyllosoma complex (Hemiptera: Reduviidae) around the
      community of Carrillo Puerto, Nayarit, Mexico.
AB  - Research on domestic and sylvatic triatomines within the community of Carrillo
      Puerto and neighboring areas of Nayarit, Mexico, documented that Triatoma
      longipennis (Usinger) and Triatoma picturata (Usinger) were infected with
      Trypanosoma cruzi (L.) in both habitats. T. picturata was the predominant species
      in both habitats. Mouse baited-traps increased the effectiveness of collecting
      sylvatic triatomines, which were difficult to sample by inspecting habitats such
      as burrows, caves, and cliffs. The colonization of sylvatic and peridomestic
      habitats by Triatoma, the occurrence of high rates of infection with T. cruzi and
      the possibility that bugs move between habitats may require modification of
      current control strategies in Mexico.

PMID- 11580036
TI  - Indirect evidence against delayed "skip-oviposition" behavior by Aedes aegypti
      (Diptera: Culicidae) in Thailand.
AB  - Mosquitoes that do not oviposit their entire batch of eggs in one location, but
      choose instead to oviposit a few eggs in several different sites exhibit skip
      oviposition. Although skip oviposition may ensure the greater distribution of
      progeny from an individual female and reduce sibling competition, it also uses
      greater maternal energy reserves, may increase the risk of adult female mortality
      and does not reduce other competition. To test the hypothesis that female Aedes
      aegypti (L.) do not oviposit all of their eggs at one time and place, we examined
      females collected with an aspirator resting inside houses in Thailand. Females (n
      = 384) were dissected and the stage and number of developing oocytes were
      enumerated. If skip oviposition is a common behavior among female Ae. aegypti,
      one would expect to find significantly fewer mature eggs (Christophers' stage V)
      in gravid females than developing oocytes in half-gravid females (Christophers'
      stage IIIa-IVb). No significant differences were found between ovaries containing
      immature or mature oocytes, even when the data were stratified by female body
      size and when immature oocytes that potentially could undergo resorption
      (Christophers' stages IIIa-IIIb) were excluded from the analysis. We found no
      evidence that skip oviposition over several days is a common behavior among
      domestic populations of Ae. aegypti at the end of the rainy season in this region
      of Thailand.

PMID- 11580038
TI  - Resistance to Bacillus sphaericus in Culex pipiens (Diptera: Culicidae):
      interaction between recessive mutants and evolution in southern France.
AB  - In southern France, failure to control Culex pipiens L. with Bacillus sphaericus
      Neide toxin (Bs) was first detected in 1994, at the extreme east of the Languedoc
      Roussillon coast. This failure was due to a single recessive mutant, sp-1R. Two
      complementary strategies were used to test whether sp-1R had invaded the Bs
      controlled area by 1998. First, a strain (BP) was selected from resistant larvae
      sampled in the western part of the Bs-controlled area. In BP strain, resistance
      involved a single recessive gene, sp-2R, distinct from sp-1R, that conferred a
      similarly high resistance in the homozygous state (approximately 6,000-fold).
      Combining one copy of sp-1R and one of sp-2R conferred a > 100-fold resistance.
      Second, Bs-resistance was monitored among the offspring of field females crossed
      to sp-1RR homozygous males. Females were sampled in 20 localities of southern
      France and three localities of the Llobregat delta (Barcelona, Spain) where C.
      pipiens control is also intensive. The 537 females in the study produced enough
      larvae to infer their genotype: 462 progenies were susceptible and the survival
      rate of 51 others was explained by the presence of sp-1R and/or sp-2R. The
      remaining 24 cases indicated that other factors could confer resistance when
      combined with sp-1R. The current data showed that, even when recessive, resistant
      mutants can rapidly increase in frequency, providing some interactions that
      protect them from disappearance. We discuss the consequences of this finding on
      the current strategies aimed to avoid or delay resistance in the pests controlled
      with B. sphaericus or B. thuringiensis Berliner toxins.

PMID- 11580037
TI  - Precipitation and temperature effects on populations of Aedes albopictus
      (Diptera: Culicidae): implications for range expansion.
AB  - We investigated how temperature and precipitation regime encountered over the
      life cycle of Aedes albopictus (Skuse) affects populations. Caged populations of
      A. albopictus were maintained at 22, 26, and 30 degrees C. Cages were equipped
      with containers that served as sites for oviposition and larval development. All
      cages were assigned to one of three simulated precipitation regimes: (1) low
      fluctuation regime - water within the containers was allowed to evaporate to 90%
      of its maximum before being refilled, (2) high fluctuation regime - water was
      allowed to evaporate to 25% of its maximum before being refilled, and (3) drying
      regime - water was allowed to evaporate to complete container dryness before
      being refilled. Greater temperature and the absence of drying resulted in greater
      production of adults. Greater temperature in combination with drying were
      detrimental to adult production. These precipitation effects on adult production
      were absent at 22 degrees C. Greater temperatures and drying treatments yielded
      higher and lower eclosion rates, respectively and, both yielded greater
      mortality. Development time and size of adults decreased with increased
      temperatures, and drying produced larger adults. Greater temperatures resulted in
      greater egg mortality. These results suggest that populations occurring in warmer
      regions are likely to produce more adults as long as containers do not dry
      completely. Populations in cooler regions are likely to produce fewer adults with
      the variability of precipitation contributing less to variation in adult
      production. Predicted climate change in North America is likely to extend the
      northern distribution of A. albopictus and to limit further its establishment in
      arid regions.

PMID- 11580039
TI  - Isolation and characterization of Borrelia parkeri in Ornithodoros parkeri
      (Ixodida: Argasidae) collected in Colorado.
AB  - This study describes the identification of Borrelia parkeri spirochetes in
      Colorado. Two isolates of B. parkeri (6230 and 6232) were recovered from
      Ornithodoros parkeri Cooley ticks collected at an inactive prairie dog town in
      Moffat County. Both isolates were partially characterized by sequencing and
      subsequent parsimony and neighbor-joining analyses of appropriate regions of the
      16S ribosomal RNA, flagellin and P66 genes. Analyses of the 16S gene sequences
      from the Colorado isolates indicated that they were more closely related to B.
      parkeri and B. tucatae than to B. hermsii or the other species of Borrelia
      investigated in this study. Additional analyses of amino acid sequences for
      flagellin and P66, however, clearly demonstrated that isolates 6230 and 6232 were
      most closely related to B. parkeri. The possible significance of B. parkeri as an
      agent of human disease is discussed.

PMID- 11580040
TI  - Mitochondrial DNA sequences of triatomines (Hemiptera: Reduviidae): phylogenetic
      relationships.
AB  - The phylogenetic relationships among 18 species of Triatominae were inferred
      based on mitochondrial DNA (mtDNA) sequences. The species of Triatoma included 11
      belonging to the infestans complex [T. infestans (Klug), T. guasayana Wygodzinsky
      & Abalos, T. sordida (Stal), T. platensis Neiva, T. brasiliensis Neiva, T.
      rubrovaria (Blanchard), T. vitticeps (Stal), T. delpontei Romana & Abalos, T.
      maculata (Erichson), T. patagonica Del Ponte, and T. matogrossensis Leite &
      Barbosa] and four others of the same genus but of different complexes [T.
      circummaculata (Stal), T. protracta (Uhler), T. dimidiata (Latreille), and T.
      mazzottii Usinger]. As possible outgroups we used Mepraia spinolai Mazza,
      Panstrongylus megistus (Burmeister), and Rhodnius prolixus Stal. We analyzed
      mtDNA fragments of the 12S and 16S ribosomal RNA genes from each of the 18
      species, as well as of the cytochrome oxidase I (COI) gene from nine. The 12S,
      16S, and COI gene sequences were analyzed individually and combined. All of the
      phylogenetic analyses unambiguously supported two clusters: one including T.
      infestans, T. platensis, and T. delpontei, and the other T. sordida and T.
      mutagrossensis. Inclusion of T. circummaculata into the infestans complex was
      confirmed, although this is in disagreement with the morphological
      classification. On the other hand, our analyses showed that T. dimidiata is
      closely related to a phylosoma complex species, T. mazzottii. This is consistent
      with the tentative classification previously made based on morphological
      characters. The issue of the monophyly of the genus Triatoma remains unresolved.

PMID- 11580041
TI  - Life cycle of Ixodes pacificus (Acari: Ixodidae): timing of developmental
      processes under field and laboratory conditions.
AB  - The developmental timing of Ixodes pacficus Cooley & Kohls, the primary vector of
      the Lyme disease spirochete and the agent of human granulocytic ehrlichiosis in
      the far-western United States, was determined under field and laboratory
      conditions. During their seasonal peaks of abundance, each of the three parasitic
      stages of L. pacificus, both fed and unfed, was placed inside silk-screen
      packets. These packets were apportioned between four topographic exposures of two
      hilltop sites in northwestern California. The sites differed in vegetational
      composition and elevation: the first (elevation 390 m) was dominated by woodland
      grass, the second (elevation 914 m) by chaparral. The timing of oviposition,
      larval eclosion, molting, and mortality were recorded in the field every 2-3 wk
      for 2.5 yr. Microenvironmental temperatures were measured on all four exposures
      at both sites. Accelerated developmental rates of all three stages were
      correlated with warmer soil temperatures and the time of placement in the field.
      In the laboratory, replete female I. pacificus maintained under uniform
      environmental conditions sustained constant preovipositional and prehatch periods
      independent of date-of-feeding. In the field, all unfed stages survived through
      one active feeding season with most larvae and nymphs remaining in behavioral
      diapause between late summer and early spring. No life stage survived through two
      active feeding periods which suggests that cohorts do not overlap. We concluded
      that I. pacificus takes a minimum of 3 yr to complete its life cycle in
      northwestern California.

PMID- 11580042
TI  - Stercorarial shedding and transtadial transmission of hepatitis B virus by common
      bed bugs (Hemiptera: Cimicidae).
AB  - Transtadial persistence and stercorarial shedding of hepatitis B virus (HBV) in
      common bed bugs, Cimex lectularius L., was studied by using experimental
      infectious blood feedings, infectious intrathoracic inoculations, and virus
      detection by polymerase chain reaction and Southern hybridization. Results showed
      that HBV persisted after an infectious blood meal in bed bug bodies for up to 35
      d after the infectious blood meal. It was passed transtadially through one molt
      regardless of instar, was shed in fecal droplets for up to 35 d after the
      infectious blood meal, but was not passed transovarially. In bugs inoculated
      intrathoracically, HBV was detected for 21 d postinoculation. Previous studies
      detected the hepatitis B surface antigen found on both infectious and
      noninfectious particles in bed bugs. In this study, the presence of nucleic acids
      amplified from a conserved core region of the viral genome in bodies and feces of
      C. lectularius suggests that the HBV virus may be mechanically transmitted in
      feces or when bugs are crushed, during feeding.

PMID- 11580043
TI  - Stable, germ-line transformation of Culex quinquefasciatus (Diptera: Culicidae).
AB  - A Hermes-based transposable element transformation system incorporating an
      enhanced green fluorescent protein (EGFP) marker was used to produce two
      transgenic lines of Culex quinquefasciatus (Say). The transformation frequency
      was approximately 12% and transformation of Culex was shown to be dependent on
      the presence of Hermes transposase. Injected Culex embryos were treated with four
      different heat shock regimes, two of which produced transformed individuals.
      These individuals were mated with wild-type mosquitoes and produced offspring
      which expressed the dominant EGFP gene in Mendelian ratios predicted for the
      stable integration of a gene at a single locus. The two transformed lines
      displayed distinct patterns of phenotypic expression, the expression of which has
      remained stable after fifteen generations. In these transgenic lines both the
      Hermes element and flanking plasmid DNA integrated into the Culex genome, as has
      been previously seen in Hermes-mediated transgenic strains of Aedes aegypti (L.).
      The high frequency of Culex transformation together with the dependence on the
      presence of Hermes transposase suggests that, as for Ae. aegypti, this mode of
      transposition into the germ-line genome occurs by an alternate mechanisms to the
      cut and paste type of transposition seen for this element in other insect species
      and in the somatic nuclei of mosquitoes. This is the first report of the genetic
      transformation of a species in the genus Culex and demonstrates that this
      medically important mosquito species can now, along with several other Culicine
      and Anopheline mosquito species, be genetically manipulated.

PMID- 11580044
TI  - Bacterial and fungal biomass responses to feeding by larval Aedes triseriatus
      (Diptera: Culicidae).
AB  - We investigated the effect of different densities (0, 20, or 40) of developing
      larval Aedes triseriatus (Say) on bacterial abundance, bacterial productivity,
      and leaf fungal biomass in a microcosm experiment. Larvae in the low-density
      treatment developed normally, but larvae at the high density were significantly
      slower to develop. Both bacterial abundance (direct microscopic counts) and
      bacterial productivity (3H-leucine incorporation rates) on leaf material were
      significantly lower in the presence of larvae. Bacterial abundance in the water
      column did not change significantly with treatment, but bacterial productivity
      varied with time and declined significantly at both larval densities. Bacteria on
      the walls and bottom of the containers also were less abundant and significantly
      less productive in the presence of larvae. Aside from presence/absence effects,
      there was no clear evidence that larval impacts were density-dependent. Leaf
      associated fungal biomass, as measured by ergosterol levels, varied with time but
      was not significantly affected by any treatment, suggesting most fungal tissue
      was incorporated in the leaf matrix and unavailable to larvae. Based upon
      estimated biomass accrual and respiration of larvae, it appears that bacterial
      biomass and production were insufficient to account for carbon demands of growing
      larvae. Because fungal biomass and leaf mass likely contributed little to gross
      larval demands, other carbon sources (e.g., protozoa and extracellular microbial
      components) were probably used by larvae. Although apparently insufficient for
      all larval carbon demands, bacterial and leaf fungal biomass may be adequate for
      other larval nutritional needs (i.e., nitrogen and essential lipids).

PMID- 11580045
TI  - Detection of dengue viral RNA in Aedes aegypti (Diptera: Culicidae) exposed to
      sticky lures using reverse-transcriptase polymerase chain reaction.
AB  - Active surveillance for dengue (DEN) virus infected mosquitoes can be an
      effective way to predict the risk of dengue infection in a given area. However,
      doing so may pose logistical problems if mosquitoes must be kept alive or frozen
      fresh to detect DEN virus. In an attempt to simplify mosquito processing, we
      evaluated the usefulness of a sticky lure and a seminested reverse-transcriptase
      polymerase chain reaction assay (RT-PCR) for detecting DEN virus RNA under
      laboratory conditions using experimentally infected Aedes aegypti (L.)
      mosquitoes. In the first experiment, 40 male mosquitoes were inoculated with 0.13
      microl of a 10(4) pfu/ml DEN-2 stock solution. After a 7-d incubation period, the
      mosquitoes were applied to the sticky lure and kept at room temperatures of 23-30
      degrees C. Following 7, 10, 14, and 28 d application, 10 mosquitoes each were
      removed from the lure, pooled, and assayed for virus. DEN virus nucleic acid was
      clearly detectable in all pools up to 28 d after death. A second study evaluated
      sensitivity and specificity using one, two, and five DEN-infected mosquitoes
      removed after 7,10, 14, 21, and 30 d application and tested by RT-PCR. All four
      DEN serotypes were individually inoculated in mosquitoes and evaluated using the
      same procedures as experiment 1. The four serotypes were detectable in as few as
      one mosquito 30 d after applications to the lure with no evidence of cross
      reactivity. The combination of sticky lures and RT-PCR show promise for mosquito
      and dengue virus surveillance and warrant further evaluation.

PMID- 11580046
TI  - Infestation of a bird and two cats by larvae of Plodia interpunctella
      (Lepidoptera: Pyralidae).
AB  - The larvae of Plodia interpunctella (Hubner), commonly known as the Indian meal
      moth, often cause enormous losses in stored food supplies. We present three
      clinical case reports of accidental infestation by P. interpunctella larvae in
      two domestic cats and one parakeet. A larva gained entry into the avian host and
      subsequently migrated to the brain. It was alive, covered with "silk-like" fibers
      and confirmed to be a fourth instar. Plodia interpunctella larvae were excised
      with forceps from the subcutaneous tissues of the ear and neck of two cats in a
      different household. Previous reports of infestation by P. interpunctella larvae
      in vertebrates are unknown.

PMID- 11580047
TI  - Suppression of mosquito (Diptera: Culicidae) and black fly (Diptera: Simuliidae)
      blood feeding from Hereford cattle and ponies treated with permethrin.
AB  - The blood feeding of mosquitoes and black flies from Hereford cattle and ponies
      treated with commercial formulations of permethrin was evaluated using an animal
      enclosure trap sample system that allowed comparison of insect blood-feeding
      levels between treated and nontreated animals. Blood feeding of both Aedes
      dorsalis Meigen and A. melanimon Dyar from heifers treated with pour-on
      concentrate and whole body spray treatments was reduced significantly by 79-88%
      at 4 d posttreatment, with apparent but not significant reductions of 61-68% at
      11 d posttreatment. Simulium bivittatum Malloch and S. griseum Coquillett blood
      feeding was reduced significantly by 96% to >99% at 4 d posttreatment, but
      apparent reductions of 30-87% at 11 d posttreatment were not significant. Blood
      feeding of S. bivittatum from ponies treated with a permethrin fly wipe was
      reduced significantly by 98 and 87% at 1 and 7 d posttreatment, respectively. No
      evidence of treatment-induced mortality was observed for recently blood-fed
      female mosquitoes or black flies captured from treated animals and held for 24 h.
      The potential benefit of using permethrin to protect livestock from insect
      transmitted pathogens was estimated with a model based on level of host attack,
      pathogen infection rate in the vector, and suppression of blood feeding.
      Suppression of blood feeding by 90% is predicted to prevent the exposure of a
      host to a pathogen for up tolO d at 1,000 insect feedings per d when the vector
      population infection rate is one insect per 1,000. If insect feedings are lower
      (100/d) and the insect infection rate remains at one per 1,000, protection is
      predicted for 100 d. In contrast, a 90% suppression of blood feeding is predicted
      to provide protection for less than 1 d at 1,000 feeding per day and a vector
      infection rate of one insect per 100.

PMID- 11580048
TI  - Respiratory gas exchange in the flea Xenopsylla conformis (Siphonaptera:
      Pulicidae).
AB  - Respiratory gas exchange was measured in various developmental stages of the flea
      Xenopsylla conformis mycerini (Rothschild, 1904) originating from the central
      Negev in Israel. Gas exchange in fleas was measured using a flow-through
      respirometry system that monitored CO2 emission. Lowest metabolic rates were
      found in the cocooned stage, which included prepupae, early stage pupae, late
      stage pupae, and preemerged adults. Newly emerged adults and feeding larvae had
      metabolic rates 2.5-3.0 times greater than those for the cocooned stages. Highest
      rates of gas exchange were found in feeding fleas. The low metabolic rates of the
      cocooned stages is thought to contribute to their ability to survive for longer
      periods than free-living larvae and adults.

PMID- 11580049
TI  - Overproduced esterases in Culex pipiens quinquefasciatus (Diptera: Culicidae)
      from Vietnam.
AB  - The electrophoretic polymorphism of loci encoding for 10 enzymes was studied in
      Culex p. quinquefasciatus Say from six localities of Vietnam. The analysis of 11
      "neutral genes" showed that differentiation among samples was low, but
      significant (Fst = 0.06), and significantly related to geographic distance
      between sample sites. These results are similar to those observed in other
      countries (Europe and west Africa). A single type of overproduced esterases (A2
      B2) was observed, and its frequency was high (60-100%) in all samples. This
      situation is in sharp contrast with that observed in other countries of South
      East Asia (China, South Korea and Japan), where two or more types of overproduced
      esterases have been reported. A map summarizing the geographic distribution of
      Asian Cr. p. quinquefasciatus with overproduced esterases is provided.

PMID- 11580050
TI  - The first documented forensic entomology case in Thailand.
AB  - The forensic entomology case described herein is the first such case documented
      in Thailand. A mummified corpse of a 32-yr-old man was discovered in a forested
      habitat, with the larvae of six species of flies (Diptera) found in association
      with the corpse at the time of its discovery, i.e., those of Hydrotaea (=Ophyra)
      spinigera Stein (family Muscidae), Piophila casei (L.) (family Piophilidae),
      Megaselia scalaris (Loew) (family Phoridae), Sagus sp. (family Stratiomyidae),
      and larvae of two unidenitified flesh fly species (family Sarcophagidae). The
      presence and age of the larval specimens of P. casei, M. scalaris, and H.
      spinigera gave entomological evidence that the postmortem interval for the corpse
      was 3-6 mo. This report also documets some of the forensically important fly
      species that occur in Thailand.

PMID- 11580051
TI  - Ultrastructure of endocrine cells from the abdominal midgut epithelium of
      Lutzomyia longipalpis (Diptera: Psychodidae).
AB  - Transmission electron microscopy (TEM) was used to study two types of endocrine
      cells front the midgut of adult female Luttzomyia longipalpis (Lutz & Neiva).
      Endocrine cells rarely have been observed in Nematocera, even using TEM, and were
      present in small numbers dispersed among the monolayer of midgut digestive
      epithelial cells. Triangular shaped "closed" cells were observed along the
      basement membrane, bounded on each side by digestive cells; these cells closed
      distally before reaching the epithelial lumen. These endocrine cells appeared to
      deliver active granules that were secreted through a cellular membrane into the
      hemolymph. A second cell type occupied a similar position to the closed cells,
      but opened into the midgut lumen via microvilli, where the secretory products may
      be delivered. Each cell type possessed both electron-lucent and electron-dense
      vesicles with secretory granules which may indicate different stages in
      maturation and activity. These granular secretory products are probably
      peptidergic substances, with secretion mediated by diet via basal and baso
      lateral receptors that were bound to membranes or microvilli.

PMID- 11580052
TI  - Scanning electron microscopy of Aedes lineatopennis (Diptera: Culicidae) eggs.
AB  - The eggs of Aedes lineatopennis (Ludlow) are described by means of a scanning
      electron microscopy. The Ae. lineatopennis egg has a rather boat-shaped,
      fragmented micropylar collar, and membrane-like wall enclosing many tubercles of
      exochorionic sculpture.

PMID- 11580053
TI  - Scanning electron microscopy of the third-instar Piophila casei (Diptera:
      Piophilidae), a fly species of forensic importance.
AB  - The morphology of third-instar Piophila casei (L.) is described by means of
      scanning electron microscopy. Features of the anterior cephalic region and
      creeping welts that are used in larval skipping and creeping, respectively, are
      highlighted. Morphological features classically used for larval identification
      are also illustrated.

PMID- 11580054
TI  - Failure of a permethrin treatment regime to protect cattle against bluetongue
      virus.
AB  - Holstein heifers in a confined feedlot setting on a southern California dairy
      were either sprayed individually along the ventral midline using 0.2% permethrin
      (250 ml/animal) (two pens) or were not treated (two pens). Treatments (n = 6
      dates) were applied every 2 wk during the peak fall bluetongue virus transmission
      season (22 August-29 October). Animals seronegative for bluetongue virus
      antibodies at the initial bleeding on 15-18 September (n - 106 in the treatment
      pens and n = 117 in the control pens) were bled again for testing 2 mo later (12
      13 November). Seroconversion rates were not significantly different: 56% for the
      treated animals and 48% for the controls (P > 0.2). The area has many essentially
      contiguous, confinement dairies with wastewater ponds that produce large numbers
      of Culicoides sonorensis Wirth & Jones, the primary bluetongue virus vector.
      Further, these dairies presumably provided a large reservoir of virus-infected
      cattle to infect vectors in the immediate area. Under these severe virus
      challenge conditions, permethrin applied at 2-wk intervals failed to reduce
      exposure to bluetongue virus.

PMID- 11580055
TI  - Analysis of salivary gland proteins of the mosquito Anopheles darlingi (Diptera:
      Culicidae).
AB  - The salivary proteins of Anopheles darlingi Root, the principal vector of malaria
      in the Amazon Region, Brazil, were analyzed. Comparison of the protein profiles
      between adult males and females revealed that most of the polypeptides are
      present in both sexes, but female-specific polypeptides also were observed. SDS
      PAGE analysis of sugar-fed female mosquitoes with ages varying from 1 to 10 d
      after adult emergence indicated that the proteins start to be accumulated in the
      first day of life and are present throughout the period analyzed. Analysis of
      blood-fed mosquitoes showed no differences in salivary proteins when compared
      with sugar fed ones, suggesting that there is no specific protein induced by
      blood. The protein profiles of the salivary glands dissected from wild-caught
      female mosquitoes from different geographical regions of Brazil were compared and
      some differences were observed.

PMID- 11580056
TI  - A retrospective study on the disappearance of blood lead in cattle with
      accidental lead toxicosis.
AB  - Lead poisoning in cattle and other food animals is of public health significance
      because of the potential for human exposure to lead through ingestion of
      contaminated meat and milk products derived from lead-poisoned animals. In
      Michigan, lead poisoning in livestock is a reportable disease, and positive
      cattle are quarantined until they test negative (<0.05 ppm blood lead). There is
      surprisingly little information on blood lead kinetics in cattle. The half-life
      has been variably reported as 9 weeks and 1-2 months. Because these data did not
      fit those obtained from cases received at the Michigan State University Animal
      Health Diagnostic Laboratory, a retrospective study was conducted to review all
      cases of accidental lead poisoning in cattle between 1990 and 1998. This
      information is needed to estimate when quarantined lead-poisoned cattle can be
      released. The results showed that the half-life of blood lead was quite variable
      and ranged from 48 to 2,507 days. The shortest half-lives (48, 56, and 57 days)
      were found in a lactating herd of 20-month-old heifers. The longest half-life,
      2,507 days, was found in a 9-month-old castrated bull, which ingested a discarded
      automobile battery. Of the 24 animals monitored, only 8/24 (33%) had half-lives
      between 6 and 14 weeks. In conclusion, the half-life of blood lead is difficult
      to predict in accidental cases of cattle poisoning.

PMID- 11580057
TI  - Seroconversion and abortion in cattle experimentally infected with Brucella sp.
      isolated from a Pacific harbor seal (Phoca vitulina richardsi).
AB  - Previously unrecognized Brucella species have been isolated from a number of
      marine mammals, including harbor seals (Phoca vitulina richardsi) in the Puget
      Sound area of the state of Washington. Because of the presence of dairy herds in
      proximity to the harbor seal populations, a study was conducted to determine the
      effects of the harbor seal Brucella isolate in experimentally inoculated cattle.
      Six pregnant cattle were exposed by intravenous injection (n = 3) or
      intraconjunctival inoculation (n = 3). Two pregnant cows were intravenously
      injected with saline and served as controls. All of the cows receiving the
      Brucella seroconverted on 1 or more tests commonly used for the detection of
      Brucella abortus infection. Two of the cattle receiving the intravenous
      inoculation aborted, and brucellae were demonstrated in the fetuses and dams
      immediately following abortion. The remaining 4 Brucella-inoculated animals and
      their fetuses were culture negative for the organism at 14 weeks postinoculation.
      Results of this study indicate the marine mammal Brucella is capable of producing
      seroconversion and abortion in cattle but is less pathogenic in that species than
      B. abortus.

PMID- 11580058
TI  - Evaluation of diagnostic tests for the detection of classical swine fever in the
      field without a gold standard.
AB  - Knowledge of the sensitivity of diagnostic tests for infectious diseases under
      field conditions can be used to design a surveillance program that increases the
      effectiveness of the control policy. In this study, the sensitivity of tests for
      the detection of classical swine fever (CSF) virus (CSFV) under field conditions
      was estimated without knowledge of the true disease status of the animals tested.
      During the CSF epidemic of 1997-1998 in The Netherlands, tonsil samples from pigs
      of CSF suspect farms were collected for laboratory diagnosis of CSE These
      specimens were tested in a fluorescence antibody test (FAT1) for the presence of
      CSFV antigen. When at least 1 specimen in a particular sample series from a farm
      was positive, this farm was declared CSFV infected. Specimens of that series,
      either FAT1 negative (98) or FAT1 positive (127), were subsequently tested again
      (FAT2). After that, a suspension was made of the remaining tissue, and this
      suspension was evaluated with a virus isolation test. In total, 225 tonsil
      specimens were examined. A statistical model was formulated, and the sensitivity
      of the 3 tests and the prevalence of positive specimens in the sample were
      estimated by the method of maximum likelihood. The sensitivity of the FAT1, the
      test that was used for confirmation of CSFV infection in a pig herd, was
      approximately 78% (95% confidence interval [CI] = 62-92%). The effectiveness of
      the selection process of animals on the farm by the veterinarian was estimated to
      be 77% (64-87%). The sensitivity of the combination of FAT1 and FAT2 (60%)
      indicates that at least 5 animals should be selected on a CSF-suspect farm to
      gain a detection probability for CSFV of 99%.

PMID- 11580059
TI  - The use of a neutralizing monoclonal antibody to detect infections of equine
      herpesvirus type 2 (EHV-2).
AB  - A blocking enzyme-linked immunosorbent assay (ELISA) was developed to detect
      antibodies to equine herpesvirus 2 in serum samples of horses. By measuring the
      binding to a single epitope, this blocking ELISA gives a good picture of the
      antibody status in the animal. The test is based on a monoclonal antibody with
      neutralizing activity and had a sensitivity of 94% and a specificity of 100%.
      Antibodies due to newly acquired infection in foals were successfully detected
      with this blocking ELISA.

PMID- 11580060
TI  - The use of polymerase chain reaction assay to diagnose proliferative gill disease
      in channel catfish (Ictalurus punctatus).
AB  - To assess the potential of a polymerase chain reaction (PCR) assay as a
      diagnostic tool in the detection of proliferative gill disease (PGD) in channel
      catfish (Ictalurus punctatus), PCR assays were compared with the traditional
      diagnostic methods of gill wet mounts and histology. A PCR assay using primers
      for Aurantiactinomyxon ictaluri, the actinospore associated with PGD, was
      performed with tissues from fish from commercial ponds. Using histology as the
      "gold standard," the sensitivity, specificity, and accuracy of the PCR assay were
      all >90%. In comparison, the wet mount examinations had a lower sensitivity and
      specificity. Using the chi-square test and a test for strength of association,
      there was a significant, strong association between results obtained by PCR and
      those obtained by the other 2 methods. These results demonstrate that the PCR
      assay is a good diagnostic tool for the detection of PGD.

PMID- 11580061
TI  - Longitudinal evaluation of bovine mammary gland health status by somatic cell
      counting, flow cytometry, and cytology.
AB  - Bovine mastitis phases induced by Staphylococcus aureus were assessed in 6
      lactating cows before challenge and at 1, 4-8, and 9-14 days postinoculation
      (dpi). Milk lymphocytes, macrophages, and polymorphonuclear cells (PMN) were
      counted by conventional (manual) cytology, identified by CD3+ and CD11b+
      immunofluorescence and counted by flow cytometry (based on leukocyte forward and
      side light scatter values). Somatic cell counts (SCC) and recovery of bacteria
      were recorded at the same times. Preinoculation samples showed a lymphocyte
      dominated composition. At 1 dpi, the percentage of PMN increased and that of
      lymphocytes decreased. At 4-8 dpi, PMN were predominant, but the percentage of
      mononuclear cells increased above that at 1 dpi and further increased by 9-14 dpi
      (when lymphocytes approached prechallenge values). Based on leukocyte
      percentages, 3 indices were created from the data: 1) the PMN/lymphocyte
      percentage ratio (PMN/L), 2) the PMN/macrophage percentage ratio (PMN/M), and 3)
      the phagocyte (PMN and macrophage)/lymphocyte percentage ratio (Phago/L).
      Significant correlations were found between cytologic and flow cytometric data in
      all of these indicators (all with P < or = 0.01). These indices identified
      nonmastitic, early inflammatory (1-8 dpi), and late inflammatory (9-14 dpi)
      animals. In contrast, SCC and bacteriology did not. Although sensitivity of the
      SCC was similar to that of Phago/L, the specificity of SCC was almost half that
      of the Phago/L index. Based on flow cytometry indicators, an algorithm for
      presumptive diagnosis of bovine mastitis was developed. Flow cytometry provides
      results as valid as those obtained by conventional (manual) cytology, shows
      greater ability to identify mastitic cases than does SCC, and may identify 3
      mammary gland health-related conditions.

PMID- 11580062
TI  - Use of detergent extracts of Brucella abortus RB51 to detect serologic responses
      in RB51-vaccinated cattle.
AB  - Serologic responses to the newly introduced rough Brucella abortus vaccine strain
      RB51 have been determined in a dot-blot format using gamma-irradiated RB51 cells
      as the antigen. Because gamma-irradiated cells are not easily prepared and the
      signal from cells was not always reliable, an alternative antigen was sought.
      Detergent extracts of B. abortus RB51 were prepared using zwittergent 3-14,
      Triton X-100, and sodium dodecyl sulfate (SDS) and examined in a dot-blot format.
      Zwittergent 3-14 extracts and gamma-irradiated RB51 cells gave the same titers.
      Unlike gamma-irradiated RB51 cells, zwittergent 3-14 extracts produced signals
      consistently, and the signals were easily interpreted. Triton X-100 extracts
      interfered with signal development, and SDS extracts resulted in a high
      background signal. Western blot analyses revealed several outer membrane proteins
      in the zwittergent 3-14 extract. The major antigens in the extract had apparent
      molecular weights of <20,000.

PMID- 11580063
TI  - Seroprevalence study of bovine neosporosis in Mexico.
AB  - An indirect enzyme-linked immunosorbent assay was used to obtain epidemiologic
      information on bovine neosporosis in dairy herds of the Mexican central plateau.
      Sera were collected from 1,003 cows from 50 dairy herds. Forty-three herds (group
      A) had been experiencing a high abortion rate. The abortion rates for the
      remaining 7 herds (group B) were within normal limits for Mexico. Five-hundred
      sixty-one (56%) of the 1,003 sera were positive. The seroprevalence of Neospora
      caninum antibodies was 72% (95% CI = 68-75%) in group A and 36% (95% CI = 31-40%)
      in group B. These results clearly show that infection with N. caninum is
      widespread in Mexican dairy herds, as indicated by seropositive cows in group A
      and group B herds at the time of the sample collection.

PMID- 11580064
TI  - Granulomatous encephalitis in a neurologically impaired goat kid associated with
      degeneration of Neospora caninum tissue cysts.
AB  - Congenital Neospora caninum infection was diagnosed in a Saanen goat from a farm
      in southern Brazil. The kid was unable to nurse and had difficulty rising,
      ataxia, and opistothotonos. The neurologic signs became more severe 3 days after
      birth, when it was euthanized. No gross lesions were observed at necropsy.
      Multifocal infiltrates primarily of mononuclear cells, nodular microgliosis, and
      perivascular cuffs of lymphocytes, plasma cells, and few neutrophils were
      observed in the brain, mostly in the cortex and adjacent to ventricles. Rare
      multinucleate giant cells were observed adjacent to inflammatory foci. Several
      tissue cysts with a thick wall that reacted strongly with polyclonal antiserum to
      N. caninum were in the cerebral cortex and medulla oblongata. Lesions were also
      present in heart, lungs, and liver, but N. caninum tachyzoites were not found.
      Distinguishing features in this goat kid included neurologic impairment resulting
      from congenital infection with N. caninum and the presence of granulomatous
      inflammation with rare giant cells associated with degeneration of tissue cysts.

PMID- 11580065
TI  - Haemophilus somnus bronchopneumonia in American bison (Bison bison).
AB  - Immunoperoxidase assays were performed on 21 archived formalin-fixed, paraffin
      embedded tissues from from American bison (Bison bison) with bronchopneumonia.
      Seven of the 21 bison had positive staining for Haemophilus somnus in alveolar
      exudate, visceral pleura, lung parenchyma, and chronic necrotic lesions, and H.
      somnus was isolated from tissues from 1 of these 7 animals. Results suggest that
      H. somnus is a respiratory pathogen in bison.

PMID- 11580066
TI  - In vitro detection of Shiga toxin using porcine alveolar macrophages.
AB  - Porcine alveolar macrophages were found to be highly susceptible to the cytolytic
      effects of a toxin (Shiga toxin [Stx]) produced by certain strains of Escherichia
      coli and sometimes associated with clinical disease in pigs and other animals. In
      comparison with the cells that are most commonly used for Stx detection and
      titration in vitro (namely, Vero cells), porcine alveolar macrophages appeared to
      be generally more sensitive and test results could be obtained in less time.
      Moreover, unlike Vero cells, porcine alveolar macrophages need not be
      continuously propagated to ensure immediate availability. They can simply be
      removed from a low-temperature repository, thawed, seeded, and shortly thereafter
      exposed to the sample in question. These characteristics suggest that porcine
      alveolar macrophages may be useful in developing a highly sensitive and timely
      diagnostic test for Stx.

PMID- 11580067
TI  - Detection of bovine herpesvirus-1 in peripheral blood mononuclear cells eight
      months postinfection.
AB  - Peripheral blood mononuclear cells (PBMCs) from 5 calves (3 controls and 2
      vaccinates) used in a bovine herpesvirus 1 (BHV-1) vaccine study with a BHV-1
      Cooper strain challenge were collected 6 months after challenge. The PBMCs from
      the control animals were positive by immunofluorescence for the BHV-1
      glycoprotein D (gD) while the vaccinates were negative. The PBMC samples from 4
      of the 5 animals were examined for BHV-1 DNA by polymerase chain reaction (PCR)
      and for gD immunofluorescence at 8 months after challenge. The BHV-1 DNA and
      viral antigen were detected in PBMC samples at 8 months postinfection, but no
      virus was isolated.

PMID- 11580068
TI  - Paramyxovirus infection in pigs with interstitial pneumonia and encephalitis in
      the United States.
AB  - In the last few years, newly recognized paramyxoviruses have been associated with
      severe disease in several animal species, including swine, as well as in human
      beings. Recently, a paramyxovirus was isolated from a swine herd in the
      northcentral United States that experienced an epizootic of respiratory and
      central nervous system disease. Affected pigs had interstitial pneumonia with
      necrotizing bronchiolitis and encephalitis characterized by lymphocytic
      perivasculitis and diffuse gliosis. Germ-free pigs inoculated with this isolate
      developed mild clinical illness and similar but less severe histopathologic
      lesions in lungs and brain.

PMID- 11580069
TI  - Equine monocytic Ehrlichiosis (Potomac horse fever) in horses in Uruguay and
      southern Brazil.
AB  - A disease named locally as churrio or churrido equino (i.e., equine scours) has
      occurred for at least 100 years in Uruguay and southern Brazil in farms along
      both shores of the Merin lake. This report describes cases of churrido equino and
      provides serologic, pathologic, and DNA-based evidence indicating that the
      disease is in fact equine monocytic ehrlichiosis (Potomac horse fever). Results
      of an epidemiological investigation conducted on an endemic farm are also
      presented. Clinical signs in 12 horses were fever, depression, diarrhea,
      dehydration, and sometimes colic and distal hind limb edema. Postmortem findings
      of 3 horses were of acute enterocolitis. Inclusion bodies containing ehrlichial
      organisms were found in the cytoplasm of macrophages of the large colon of 1
      horse. Eleven of the 12 horses were serologically positive to Ehrlichia risticii
      (indirect fluorescent antibody assay) and, of 3 paired samples, 2 showed
      seroconversion. Ehrlichia risticii DNA was identified by a nested polymerase
      chain reaction in peripheral blood of an affected horse. A healthy horse
      inoculated with peripheral blood from an affected horse developed the disease and
      antibodies to E. risticii. The disease had a peak incidence in March (summer) and
      was statistically associated with a marshy ecosystem near the Merin lake, where
      large numbers of Pomacea spp. (Ampullariidae) snails were found. Incidence
      density was almost 8 times higher in nonnative horses than in native horses. It
      was concluded that the previous diarrheic disease of horses known in Uruguay and
      southern Brazil as churrido equino is equine monocytic ehrlichiosis.

PMID- 11580070
TI  - Molecular identification of Candida parapsilosis from crop mucosa in a cockatiel.
AB  - A 2-month-old cockatiel was evaluated for diarrhea, dyspnea, and death.
      Histologic examination of lesions in the crop mucosa revealed hyperkeratosis and
      the presence of blastoconidia and hyphae. Positive immunohistochemical staining
      of the organisms was achieved with an antibody directed against Candida spp.
      Polymerase chain reaction amplification of DNA from crop lesion material with
      internal transcribed spacer 2 (ITS2) primers yielded fragments of approximately
      300 bp, which demonstrated 95% DNA homology with the corresponding sequence from
      a strain of Candida parapsilosis deposited in the GenBank data base. The Candida
      species in the lesion of the crop mucosa was therefore identified by DNA sequence
      analysis as C. parapsilosis.

PMID- 11580071
TI  - PCR detection of the Cryptococcus neoformans CAPS9 gene from a biopsy specimen
      from a case of feline cryptococcosis.
AB  - A polymerase chain reaction assay was developed to detect Cryptococcus neoformans
      in biopsy samples. The assay detects the CAP59 gene of Cryptococcus neoformans
      and was used to substantiate cutaneous cryptococcosis in a 5-year-old cat
      submitted to the Veterinary Medicine Center at the University of Tokyo.

PMID- 11580072
TI  - Soft tissue sarcomas in the African hedgehog (Atelerix albiventris): microscopic
      and immunohistologic study of three cases.
AB  - Three soft tissue tumors from 2 female hedgehogs were examined microscopically
      and immunohistochemically. Two tumors involved haired skin and the third one was
      vaginal. Microscopically, the cutaneous tumors had features of malignant
      peripheral nerve sheath tumor (MPNST), whereas the vaginal tumor was classified
      only as a spindle cell sarcoma. Immunohistochemically, all 3 tumors were strongly
      positive for vimentin and strongly to moderately positive for CD10 and neuron
      specific enolase but did not stain with antibody to S100 protein, an antigen
      typically present in human MPNST The cutaneous tumor from hedgehog no. 1 was
      examined ultrastructurally and the neoplastic cells resembled fibroblasts.
      Hedgehog no. 1 was euthanized at the time of the biopsy. The outcome of the other
      hedgehog was unknown.

PMID- 11580073
TI  - A simple thin-layer chromatographic method for the detection of ergovaline in
      leaf sheaths of tall fescue (Festuca arundinacea) infected with Neotyphodium
      coenophialum.
AB  - A relatively simple and inexpensive thin-layer chromatographic (TLC) method is
      described for the detection and semiquantitative measurement of ergovaline in
      leaf sheaths of tall fescue (Festuca arundinacea). Samples were finely ground and
      extracted with methanol. The extracts were filtered and the methanol was
      evaporated. The aqueous residue was extracted with hexane, followed by chloroform
      at pH 9. The chloroform extract was concentrated and further purified on a
      preparative silica gel TLC plate, developed with toluene/ethyl
      acetate/acetonitrile (50:10:40). The ergovaline band was scraped and eluted with
      methanol. The eluant was concentrated and an aliquot was applied to a silica gel
      TLC plate. The plate was developed successively with chloroform/acetone/acetic
      acid (90:10:5) and chloroform/ethanol (9:1). Ergovaline was visualized with p
      dimethylaminobenzaldehyde and sulfuric acid. Semiquantitation of ergovaline was
      achieved by comparison with a known standard of ergotamine, which was shown to
      have the same Rf as ergovaline in this system. Spike recovery of ergotamine
      averaged 60%, with a limit of detection of 200 microg/kg of dry tall fescue leaf
      sheaths. The method was applied to 15 tall fescue samples with varying degrees of
      fungal infection, and ergovaline was identified in all contaminated samples with
      endophyte infection above 15%. Thin-layer chromatography may be also applicable
      for tall fescue seed, where the ergovaline content is usually higher and the
      amount of interfering pigments is much lower.

PMID- 11580074
TI  - A prospective evaluation of the awareness, knowledge, risk factors and current
      treatment of osteoporosis in a cohort of elderly subjects.
AB  - This was a prospective cohort study of 145 seniors attending a senior's clinic
      and social day program using a self-administered questionnaire. Its objective was
      to evaluate the awareness, knowledge, risk factors and current treatment of
      osteoporosis in our two patient groups. A secondary objective was to determine
      differences between the two cohorts, and between men and women. Participants
      included 39 men and 106 women, with an average age of 76 years. Of these, 89%
      were aware of osteoporosis and 61% gave the correct definition. Awareness and
      accurate definition were less in men compared with women (p < 0.01, and p < 0.05)
      and clinic compared to day program groups (p < 0.01). Only 54% of men knew
      osteoporosis could affect them. Television, newspapers and friends were
      identified as the main source of information. Physicians ranked as fifth as a
      source of information. In all, 84% knew diet was important. Prevalence of risk
      factors other than age were < 20%, except for senescence (38%) and alcohol use
      (40%). Utilization of specific therapies for osteoporosis was only 18% overall
      with a rate of 3% in men (p < 0.01). In women, 50% and were taking calcium
      supplements compared with 15% men (p < 0.001) and for multivitamins the figures
      were 57% and 33% respectively (p < 0.05). These results show a high level of
      awareness and correct definition of osteoporosis in this cohort of patients.
      Specific therapy for prevention or treatment of osteoporosis was inappropriately
      low in the face of high risk. This study highlights the care gap in osteoporosis
      in seniors and the need for increased physician involvement in patient education
      and treatment. Proactive treatment requests from patients need to be encouraged,
      especially with the future demographic shift.

PMID- 11580075
TI  - Maternal height, childhood growth and risk of hip fracture in later life: a
      longitudinal study.
AB  - Although measures to enhance bone mineralization during childhood and adolescence
      are widely incorporated into preventive programmes against osteoporotic fracture,
      there are no published data directly linking growth rates in childhood with the
      risk of later hip fracture. We addressed this issue in a unique Finnish cohort in
      whom birth and childhood growth data were linked to later hospital discharge
      records. This permitted follow-up of 3639 men and 3447 women who were born in
      Helsinki University Central Hospital between 1924 and 1933, who went to school in
      Helsinki and still lived in Finland in 1971. Body size at birth was recorded and
      an average of 10 measurements were obtained of height and weight throughout
      childhood. We identified 112 subjects (55 men and 57 women) who sustained a hip
      fracture during 165 404 person-years of follow-up. After adjustment for age and
      sex in a proportional hazards model, we identified two major determinants of hip
      fracture risk: tall maternal height (p < 0.001) and a low rate of childhood
      growth (height, p = 0.006; weight, p = 0.01). The hazard ratio for hip fracture
      was 2.1 (95% CI 1.2-3.5) among men and women born to mothers taller than 1.61 m,
      when compared with those whose mothers were shorter than 1.54 m. The ratio was
      1.9 (95% CI 1.1-3.2) among those whose rate of childhood height gain was below
      the lowest quartile for the cohort, compared with those whose growth rate was
      above the highest quartile. The effects of maternal height and childhood growth
      rate were statistically independent of each other, and remained after adjusting
      for socioeconomic status. The patterns of childhood growth that predicted future
      hip fracture differed between boys and girls. In boys, there was a constant
      deficit in height and weight between ages 7 and 15 years among those later
      sustaining fractures; in girls, there was a progressively increasing deficit in
      weight but a delayed height gain among those later sustaining fractures. This
      epidemiologic study provides the first direct evidence that a low rate of
      childhood growth is a risk factor for later hip fracture. Whether reduced growth
      rate is a consequence of childhood lifestyle, genetic background or intrauterine
      hormonal programming, the data support measures to optimize childhood growth as
      part of preventive strategies against osteoporotic fracture in future
      generations.

PMID- 11580076
TI  - Risk factors for osteoporosis related to their outcome: fractures.
AB  - The aim of the study was to determine to what extent easy obtainable bone mineral
      density (BMD)-related risk factors are associated with the occurrence of
      fractures and to what extent changes in these determinants during a patient's
      lifetime are relevant. A cross-sectional population-based study was carried out
      on 4725 postmenopausal women, 50-80 years of age, registered with 23 general
      practitioners (GPs). The women were questioned and examined. BMD of the lumbar
      spine was measured using dual-energy X-ray absorptiometry (QDR-1000, Hologic). We
      analyzed the total population as well as a random sample of 1155 women for whom
      additional data were collected on recalled weight at age 20-30 years and on self
      reported height. Body mass index (BMI) was estimated in two ways: (2) objective
      BMI [= measured weight/(measured height)2]; (2) recalled BMI [= recalled body
      weight at age 20-30/(self-reported height)2]. Fractures (dependent variable) were
      categorized as: (1) fractures sustained during the patient's lifetime; (2)
      fractures after the age of 50 years; (3) fractures that had occurred during the 5
      years before BMD measurement took place. Multivariate stepwise backward and
      forward logistic regression analyses, using fractures as the dependent variable,
      were performed with all discrete and non-discrete variables (divided into
      quartiles). The relationship between the presence of osteoporosis and the
      presence of fractures was related to the changes in BMI (recalled BMI versus
      objective BMI). More advanced age, positive family history of fractures and BMD
      had a positive association with the presence of fractures. Low recalled BMI was a
      statistically significant predictor of 'fractures during the patient's lifetime'
      and of 'fractures after the age of 50'. Hysterectomy was associated with a higher
      prevalence of 'fractures during the patient's lifetime'. Perimenopausal
      complaints in the history seemed to be associated with a lower prevalence of
      'fractures after the age of 50'. Moderate (and heavy) occupational exercise in
      the past were associated with the presence of fractures 'after the age of 50' and
      'fractures during the past 5 years'. Sporting activities in the past showed a
      slightly positive relationship with the presence of 'fractures during the
      patient's lifetime' and 'fractures after the age of 50'. Bivariate analysis
      revealed that current smokers had not sustained significantly more fractures than
      current nonsmokers, but within the subgroup of current smokers, the prevalence of
      fractures was significantly higher among those women who had smoked for more than
      35 years. Smoking was statistically significantly associated with early
      menopause. Early menopause was not statistically significantly related to the
      presence of osteoporosis but appeared to be statistically significantly
      associated with the prevalence of fractures in the age categories over 65 years.
      The absolute risks of sustaining one or more fractures ranged from 3% to 44%.
      Women in the lowest quartile of recalled and objective BMI were often
      osteoporotic (40%). In this category, women with normal BMD had a statistically
      significant lower fracture risk than osteoporotic women. Women with a possibly
      decreased BMI were most often osteoporotic and had sustained more 'fractures
      during the past 5 years' than expected. Women who had (probably) always been
      obese were less often osteoporotic and had a much lower fracture risk. It is
      concluded that decreased BMI is associated with a higher risk of developing
      fractures at an older age. Prevention of fractures should include fall
      prevention. In addition, in lean women treatment of low BMD is important.

PMID- 11580077
TI  - Bone quality parameters of the distal radius as assessed by pQCT in normal and
      fractured women.
AB  - The aim of this study was to test the ability of some indicators of different
      aspects of bone quality (assessed by peripheral quantitative computed tomography
      in the distal radius) to discriminate between fractured and nonfractured
      individuals. The study compared 214 women aged 45-85 years, free of any bone
      affecting treatment, of whom 107 had suffered a Colles' fracture in the previous
      6 months and 107 did not. The determinations included bone tissue or mineral
      'mass' indicators (trabecular, cortical and total volumetric mineral content,
      cortical bone area); bone 'density' estimates (trabecular, cortical and total
      volumetric mineral density), and the Cartesian (rectangular) and polar moments of
      inertia as influences of cross-sectional architecture on resistance to bending
      and torsional loads, respectively. The influences of body height, weight and age
      on the tomographic indicators were minimized by adjusting the data according to
      the partial coefficients of multiple stepwise regressions. The adjusted values of
      all the indicators were lower in fractured than in nonfractured groups. The
      prevalence of fractures was directly related to the actual values of the
      indicators, rather than the age or body habitus of the individuals. The
      significance of these differences between the assessed indicators decreased in
      the following order: trabecular 'mass' > trabecular 'density' > cortical or total
      'mass' > cortical architecture > total or cortical 'density' indicators. Within
      the same type of bone, the tissue or mineral 'mass' indicators performed better
      than the 'density' indicators. The cortical bone density did not give useful
      information, probably because of technical difficulties. Odds-ratios and receiver
      operating characteristic (ROC) analyses confirmed those features. The selected
      'cut-off' values of the indicators as determined by the ROC curves (very close to
      those determined by the inflexion points of the logistic reression curves) may
      indicate reference limits to detect persons at risk of fracture according to the
      type of information provided by each variable. These results show that these
      tomographic indicators discriminate well between fractured and nonfractured
      individuals, and should be suitable to assess how total, cortical and trabecular
      bone strength in the distal radius could affect different kinds of strength
      regardless of the age or body habitus of the individual. Their ability to
      estimate fracture risk from different biomechanical points of view should be
      assessed by adequately designed, prospective studies.

PMID- 11580078
TI  - The profile of bone mineral density in chinese women: its changes and
      significance in a longitudinal study.
AB  - Bone mineral density (BMD) has been shown to be different in different ethnic
      groups. When lifestyle and diet evolve, there is a possibility of a change in the
      normal reference BMD values within an ethnic group over a period of time. As the
      osteoporotic risk uses the T-score as the bench mark, it is pertinent to evaluate
      whether such changes do occur. Two measurements, 5 years apart, of the BMD of the
      spine and the hip were made in a cohort of Chinese women in Hong Kong. A kernel
      function smoothing method, a nonparametric statistical method, was employed to
      present the BMD data. The greatest rate of bone loss was found to occur between
      50 and 59 years of age, but this rate of loss was reduced from age 60 onwards.
      The BMD values obtained in these two measurements were different from the
      previous studies in the same population and were found to be higher at the lumbar
      spine and neck of femur in women over 65 years of age. Even within the cohort,
      there seemed to be a reduction in the BMD values of the hip in a span of 5 years,
      although the differences were statistically insignificant. These studies suggest
      that BMD values could change in a population for a variety of possible reasons.
      Hence, the reference BMD values might need to be evaluated at regular intervals
      for the T-score to be meaningful.

PMID- 11580079
TI  - The effect of alendronate on fracture-related healthcare utilization and costs:
      the fracture intervention trial.
AB  - The Vertebral Fracture Arm (VFA) of the Fracture Intervention Trial (FIT) study
      demonstrated that alendronate reduced the incidence of spine, forearm and hip
      fractures in women with low bone mass and existing vertebral fractures by about
      50%. The objective of the present study was to determine the effects of
      alendronate therapy versus placebo on fracture-related healthcare utilization and
      costs. Participants were randomly assigned to double-masked treatment with
      alendronate (5 mg/day for 2 years and then 10 mg/day for 1 year) or placebo for 3
      years. For each patient experiencing a clinical fracture, we determined whether
      treatment in an emergency room, hospital, nursing home and/or rehabilitation
      hospital was a consequence of the fracture. The VFA of the FIT Study enrolled
      2027 women aged 55-81 years with low bone mass and pre-existing vertebral
      fractures from population-based listings in 11 metropolitan areas of the United
      States. We measured (1) the proportion of patients who had any fracture-related
      healthcare event and (2) the estimated cost of fracture-related healthcare
      services. Alendronate significantly reduced the proportion of patients utilizing
      fracture-related healthcare (emergency room, hospital, rehabilitation hospital or
      nursing home) by 25% (p = 0.038). Alendronate significantly reduced the costs
      associated with hip-fracture-related care by 58%, or $181 per patient randomized
      (p = 0.036). The reduction in fracture-related total costs was 35% ($190 per
      patient randomized) in the alendronate group relative to the placebo group (p =
      0.114). Alendronate thus not only reduces the incidence of clinical fractures and
      associated morbidity, but reduces the proportion of patients utilizing the
      associated healthcare resources.

PMID- 11580080
TI  - Longitudinal evaluation of morphometric X-ray absorptiometry for the
      identification of vertebral deformities.
AB  - Morphometric X-ray absorptiometry (MXA) has not been evaluated for the
      identification of incident vertebral deformities. The reliability of longitudinal
      measurements in quantitative vertebral morphometry is influenced by the precision
      of the technique. Long-term precision in vitro (weekly MXA phantom scans)
      assessed by retrospective cumulative sum (Cusum) analysis, detected one event
      during a 6-month period when the measurement process was 'out of control'.
      Inspection of service records revealed that repair work was performed around this
      timepoint. The coefficient of variation (CV) for long-term precision (vertebral
      heights) in a population-based sample of postmenopausal women ages 56 to 83, mean
      65+/-6 years (n = 48), was 4.0% for morphometric radiography (MRX), 2.9% for MXA
      using the compare facility for analysis of serial scans, and 3.2% when 'compare'
      was not used. In women with osteoporosis ages 49 to 87, mean 67+/-9 years (n =
      50). the CV was 5.0% for MRX, 4.1% for MXA using 'compare' and 8.5% without
      'compare'. Precision errors for height ratios (MRX and MXA) were greater than for
      vertebral heights. Incident deformities were identified by MRX and MXA in the
      women with osteoporosis, using point prevalence, 20% minimum reduction in
      vertebral height, and percent least significant change (LSC) in vertebral heights
      and height ratios. Semiquantitative analysis of radiographs by a radiologist
      (Genant method) was used as the gold standard. The results were similar for MRX
      and MXA, and all morphometric criteria identified a similar proportion of true
      incident deformities, although the false positive rate was generally greater for
      the height ratio approaches. MXA has good long-term precision and is comparable
      to MRX for the identification of incident deformities when scans are analyzed
      with the compare facility.

PMID- 11580081
TI  - Postal administration compared with nurse-supported administration of the
      QUALEFFO-41 in a population sample: comparison of results and assessment of
      psychometric properties.
AB  - The objective of this study was to test the psychometric properties of the
      QUALEFFO-41, an osteoporosis-specific health-related quality of life (HRQoL)
      measure, in a population sample. The study involved repeated administration of
      QUALEFFO-41 and another measure of HRQoL, the SF-36, to a stratified random
      population sample to test reliability and validity of instrument. The study was
      set in urban Harrow, Middlesex, UK and rural Cambridgeshire, UK. The participants
      were 83 males and 88 females aged 65-80+ years. Of the 230 individuals contacted
      76.5% participated. The test-retest reliability of most QUALEFFO-41 items was
      good (Kappa 0.59-0.91) but two items had lower repeatability. Internal
      consistency was also generally good, but suggestive of some redundancy for three
      domains. The QUALEFFO-41 domains in general correlated well with SF-36 domains (r
      = 0.57 to r = 0.87), suggesting good validity. The QUALEFFO-41 has been shown to
      be a reliable and valid disease-specific HRQoL measure for osteoporosis. In
      population samples, it can be administered by post, or with a professional
      available to answer queries. Some specific items perform less well than may be
      desired and there is evidence of some redundancy, but further investigation is
      required and there are not yet grounds for textual change. We recommend continued
      use of this well-validated, reliable instrument.

PMID- 11580082
TI  - 1,25-Dihydroxyvitamin D3 promotes vitamin K2 metabolism in human osteoblasts.
AB  - It has been reported that vitamin K2 (menaquinone-4) promoted 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3)-induced mineralization and enhanced gamma
      carboxyglutamic acid (Gla)-containing osteocalcin accumulation in cultured human
      osteoblasts. In the present study, we investigated whether menaquinone-4 (MK-4)
      was metabolized in human osteoblasts to act as a cofactor of gamma-glutamyl
      carboxylase. Both conversions of MK-4 to MK-4 2,3-epoxide (epoxide) and epoxide
      to MK-4 were observed in cell extracts of cultured human osteoblasts. The effect
      of 1,25(OH)2D3 and warfarin on the vitamin K cycle to cultured osteoblasts were
      examined. With the addition of 1 nM 1,25(OH)2D3 or 25 microM warfarin in cultured
      osteoblasts, the yield of epoxide from MK-4 increased. However, the conversion of
      epoxide to MK-4 was strongly inhibited by the addition of warfarin (2.5-25
      microM), whereas it was almost not inhibited by 1,25(OH)2D3 (0.1-10 nM). To
      clarify the mechanism for this phenomenon, a cell-free assay system was studied.
      Osteoblast microsomes were incubated with 10 microM epoxide in the presence or
      absence of warfarin and 1,25(OH)2D3. Epoxide reductase, one of the enzymes in the
      vitamin K cycle was strongly inhibited by warfarin (2.5-25 microM), whereas it
      was not affected by 1,25(OH)2D3 (0.1-1 nM). Moreover, there was no effect of
      pretreatment of osteoblasts with 1 nM 1,25(OH)2D3 on the activity of epoxide
      reductase. However, the activity of epoxidase, that is the gamma-glutamyl
      carboxylase was induced by the pretreatment of osteoblasts with 1 nM 1,25(OH)2D3.
      In the present study, it was demonstrated that the vitamin K metabolic cycle
      functions in human osteoblasts as well as in the liver, the post-translational
      mechanism, by which 1,25(OH)2D3 caused mineralization in cooperation with vitamin
      K2 was clarified.

PMID- 11580083
TI  - The effects of lifestyle, dietary dairy intake and diabetes on bone density and
      vertebral deformity prevalence: the EVOS study.
AB  - The risk of low and moderate energy fracture is related to bone mineral density
      (BMD). Yet it is uncertain whether the epidemiologic determinants of fracture
      risk are the same as for low bone density. The European Vertebral Osteoporosis
      Study was a population-based prevalence study of vertebral deformity in 36 age
      stratified population samples aged 50-80 years. In nearly 4000 subjects (13
      centers), BMD measurements were also made at the spine, femoral neck and femoral
      trochanter. To investigate whether effects of reported physical activity on spine
      deformity risk were mediated through BMD, we modeled these and other risk factor
      data with BMD as the dependent variate after adjusting for age, center, sex and
      body mass index (BMI). The significant determinants of vertebral deformity risk
      were also entered into logistic models of deformity risk that included BMD
      measurements as covariates. Both current and lifetime physical activity were
      positively associated with BMD. This effect was stronger with hip BMD than with
      spine BMD. Lifetime smoking exposure was associated with reduced BMD. Type 2
      diabetes mellitus was associated with increased BMD. Weak positive associations
      were found between consumption of dairy products and BMD at the three measured
      sites and these were strengthened by an interaction with measures of physical
      activity in men. Physical activity in women had the largest beneficial effect in
      lean women and in women exposed to hormone replacement therapy. When fracture
      risk was modeled with BMD as a covariate, the lifestyle and dietary determinants
      became less strongly related to vertebral deformity risk, suggesting that BMD may
      have acted as an intermediary variable. However, heavy physical activity in men
      still increased spine deformity risk after adjusting for BMD. It is concluded
      that physical activity in both genders and milk consumption in young women might
      protect against vertebral deformities in later life through their effects on bone
      density. The adverse effect of smoking on BMD was confirmed. Heavy physical
      activity in men might increase spine deformity risk even when BMD is normal.

PMID- 11580084
TI  - A simple tool to identify asian women at increased risk of osteoporosis.
AB  - Patients with low bone mineral density (BMD) have a high risk of future
      fractures, and should be actively considered for treatment to reduce their risk.
      However, BMD measurements are not widely available in some communities, because
      of cost and lack of equipment. Simple questionnaires have been designed to help
      target high-risk women for BMD measurements, thereby avoiding the cost of
      measuring women at low risk. However, such tools have previously focused on
      evaluation of non-Asian women. We collected information about numerous risk
      factors from postmenopausal Asian women in eight countries in Asia using
      questionnaires, and evaluated the ability of these risk factors to identify women
      with osteoporosis as defined by femoral neck BMD T-scores < or =-2.5. Multiple
      variable regression analysis and item reduction yielded a final tool based on
      only age and body weight. This risk index had a sensitivity of 91% and
      specificity of 45%, with an area under the curve of 0.79. Previously published
      risk indices based on larger numbers of variables performed similarly well in
      this Asian population. Large differences in risk were identified using our index
      to create three categories: 61% of the high-risk women had osteoporosis, compared
      with only 15% and 3% of the intermediate- and low-risk women, respectively. The
      low-risk group represented 40% of all women, for whom BMD measurements are
      probably not needed unless important risk factors, such as prior nonviolent
      fracture or corticosteroid use, are present. An existing population-based sample
      of postmenopausal Japanese women was used to validate our index. In this sample
      of Japanese women the sensitivity was 98% and specificity was 29%; the low-risk
      category, for whom BMD is probably unnecessary, represented 25% of all women. We
      conclude that our index performed well for classifying the risk of osteoporosis
      among postmenopausal Asian women and applying it would result in more prudent use
      of BMD technology.

PMID- 11580085
TI  - Utility of quantitative ultrasound in detecting skeletal status.

PMID- 11580086
TI  - Oral health promotion in England--time for a health check.

PMID- 11580087
TI  - An introduction to meta-analysis within the framework of multilevel modelling
      using the probability of success of root canal treatment as an illustration.
AB  - OBJECTIVE: To introduce the statistical methodology of meta-analysis within the
      framework of multilevel modelling (MLM) using an illustrative example. BASIC
      RESEARCH DESIGN: In meta-analysis it is important that the quantitative pooling
      of study results should be carried out in conjunction with careful consideration
      of the variation apparent between studies. If statistical heterogeneity is found
      to be significant, it is due, at least in part, to clinical heterogeneity. It is
      possible to account for clinical heterogeneity by including covariates that are
      thought to be responsible, using meta-regression. CLINICAL SETTING: A total of 38
      studies of root canal treatment outcome were identified as being suitable for
      introducing the meta-analysis methodology. Two covariates were considered for
      modelling: a 'loose' or 'strict' (loose--incomplete radiographic healing; strict-
      complete radiographic healing) criterion for judging outcome of treatment and the
      year in which the study was performed. RESULTS: There was considerable
      statistical heterogeneity between the study results. The effect of employing
      loose criteria for judging success significantly increased the probability of
      success when compared to employing strict criteria. Furthermore, the variance
      between studies was significantly reduced when this covariate was included in the
      modelling process when compared to the variation estimated in the model which did
      not consider covariates. CONCLUSION: MLM is a good facilitator for meta-analysis
      and meta-regression.

PMID- 11580088
TI  - An evaluation of a new measure of oral health related quality of life--OHQoL
      UK(W).
AB  - OBJECTIVE: The aim was to test the reliability and validity of an instrument used
      to measure the impact of oral health on quality of life. BASIC RESEARCH DESIGN:
      The instrument tested was the indicator OHQoL-UK(W), which was developed, based
      on a general UK population's perceptions of how oral health affects life quality.
      OHQoL-UK(W) consists of a battery of 16 questions, which takes into account both
      'effect' and 'impact' of oral health on life quality, incorporating dimensions
      and an individualised weighting system. A questionnaire containing the indicator
      was administered to a sample of 500 adults. Determining associations between
      OHQoL-UK(W) scores, socio-demographic and self-reported oral health status
      assessed its construct validity. The criterion validity of the indicator was
      assessed in the absence of a 'gold standard' by correlating OHQoL-UK(W) scores to
      self-rating of oral health status. The internal reliability of the indicator was
      assessed using Cronbach's alpha. RESULTS: The response rate was 78%. Associations
      between OHQoL-UK(W) scores and self-reported number of natural teeth (P<0.01) and
      denture status (P<0.01) supported the construct validity of the indicator. In
      addition, OHQoL-UK(W) scores were associated with socio-demographic factors; age
      (P<0.05), employment status (P<0.01) and ethnicity (P<0.05). The instrument was
      also associated with self-rating of oral health status (P<0.01), supporting the
      criterion validity of the indicator. The internal reliability was high with a
      Cronbach alpha value of 0.94. CONCLUSION: OHQoL-UK (W) appears to be a valid and
      reliable measure for assessing the impact of oral health on life quality.

PMID- 11580089
TI  - A comparison of OHIP 14 and OIDP as interviews and questionnaires.
AB  - OBJECTIVE: To assess the completion rates and concurrent validity of the Oral
      Impacts on Daily Performance (OIDP) and the short form of the Oral Health Impact
      Profile (OHIP 14) in both questionnaire and interview formats. BASIC RESEARCH
      DESIGN: Cross sectional social and clinical study. Clinical setting Dental
      teaching hospital primary care department in London UK. Participants Two week
      consecutive sample of 183 patients attending setting. PARTICIPANTS: came from 19
      ethnic groups, 53% were men and 32% had attended for a dental emergency. MAIN
      OUTCOME MEASURES: Completion rates and concurrent validity for each instrument
      and in each format. RESULTS: Completion rates for OHIP 14 and OIDP were similar
      in interview format. In questionnaire format usable data were provided on 92.9%
      of the OHIP 14 but only 86.5% of the OIDP questionnaires. Completion of both
      questionnaires was related to ethnicity. The number of impacts for both measures
      and total impact scores for OHIP 14 were related to the age of the participants,
      the presence of oral disease and the order of administration of the instruments.
      Analysis of the total score for OIDP was weakened by the severe skewness of these
      data. CONCLUSIONS: The psychometric properties of OHIP 14 and OIDP were not
      related to the method of administration. However, the use of OIDP in this
      questionnaire format may result in loss of data, particularly from people who are
      not White English.

PMID- 11580090
TI  - School milk as a vehicle for fluoride in the United Kingdom. An interim report.
AB  - OBJECTIVE: To consider the feasibility of using school milk as a vehicle to
      deliver fluoride to children, suffering from high rates of dental disease, in
      socially deprived districts. METHOD: The legal aspects of adding fluoride to milk
      and availability of milk subsidies were updated. The organisational requirements
      of using school milk as a vehicle for fluoride were investigated and the
      consultation process established. The uptake of fluoridated milk was monitored
      and the fluoridated milk was subjected to rigorous quality control. The costs
      involved in running a scheme were calculated. OUTCOME: Fluoridated milk can now
      be called milk with added fluoride and to date the product has attracted
      subsidies from the European Economic Community and from the Welfare Foods Section
      in the Department of Health. The demonstration scheme in St. Helens, Merseyside,
      generated interest from neighbouring health authorities leading to the subsequent
      expansion of the programme. By working with the dairy, recommendations to improve
      the quality of school milk have been developed. The main organisations involved
      in running school based milk fluoridation schemes have been encouraged by the low
      costs involved. CONCLUSION: The UK programme has demonstrated that it is feasible
      to use school milk as a vehicle to deliver fluoride on a community basis.
      Attention must be given to improving the quality and particularly the temperature
      control of school milk.

PMID- 11580091
TI  - Dental check-up intervals and caries preventive measures received by adolescents
      in Finland.
AB  - OBJECTIVE: The aim was first to estimate the mean length of dental examination
      intervals and the mean number of preventive procedures in two Finnish towns
      during the periods of 1990-1992 and 1993-1995. Secondly, to ascertain whether the
      length of the check-up interval and the intensity of prevention varied according
      to the caries experience at the beginning of a treatment period. Participants A
      random sample of all 12- and 15-year-old children was drawn in 1992 and 1995 in
      the towns of Jyvaskyla and Kuopio. METHOD: Oral health records obtained from
      public dental clinics were used for gathering the data on dental check-ups, DMFT
      and all preventive and treatment measures during the previous three years. The
      data were available for 267 and 590 subjects in 1992 and 1995, respectively.
      RESULTS: For 12-year-old children in 1990-1992, the mean length of check-up
      interval was 13.0 months in Kuopio and 12.4 months in Jyvaskyla, while in 1993
      1995 it was 18.1 months and 16.1 months, respectively. Among 15-year-old children
      in 1990-1992, the mean was 12.3 in Kuopio and 14.7 in Jyvaskyla. During the
      latter period the interval was 1.2 months longer (P<0.05) in Kuopio, but there
      was no lengthening in Jyvaskyla. Fluoride varnish applications, sealants, and
      instruction in oral hygiene were the most commonly used preventive measures.
      Practically no other fluoride methods than varnish applications were performed in
      dental clinics. Prevention seemed to be based mainly on procedures performed by
      the staff at the dental clinics and less attention was paid to the promotion of
      self-care. There was very little difference in the mean length of check-up
      interval and prevention between children who were caries free at the beginning of
      the treatment period and those with present or past caries experience.
      CONCLUSION: Between 1990-1992 and 1993-1995, the frequency of dental check-ups
      and the number of preventive procedures decreased. There was no indication of an
      increased caries frequency. Prevention appeared to be stereotyped and often had
      little relevance to the actual needs of the individual patient.

PMID- 11580092
TI  - Oral health status of an indigenous adult population of Central America.
AB  - OBJECTIVE: To determine the caries experience and periodontal disease status in
      adults of an indigenous rural community of Guatemala, and assess the suitability
      for longitudinal investigations. BASIC RESEARCH DESIGN: This investigation
      comprised an initial screen (Study I) and a more detailed periodontal examination
      (Study II). In Study I, caries and gingivitis levels were determined. In Study
      II, pocket probing depths (PPDs) and clinical attachment levels (CALs) were
      recorded on all teeth excluding third molars. CLINICAL SETTING: Tzununa,
      Guatemala, Central America. PARTICIPANTS: Studies I and II were conducted in 120
      adults 3 18 years and 54 adults 3 25 years respectively. RESULTS: In both Studies
      I and II, tooth retention was high with a mean tooth count of 28.2 and 27.2
      respectively. Extensive soft deposits and both supra- and subgingival calculus
      were almost universal, although gingivitis was less than expected (Study I: Mean
      percentage of sites bleeding on probing = 27.6). In Study I, the mean number of
      carious teeth was 8.6 and there was no statistically significant correlation with
      age. In Study II, PPD 3 5mm and CAL 3 6mm were highly prevalent (100% and 56% of
      subjects respectively), although widespread and severe disease was not evident.
      CONCLUSIONS: Despite the high caries level and the evidence of periodontal
      destruction in the majority of subjects, all study subjects had a functional
      dentition suggesting that emergency treatment remains the current priority.
      Longitudinal studies in such untreated populations would provide increased
      understanding of the role of environmental factors in disease etiology. The study
      also highlighted some methodological issues pertinent to conducting studies in
      remote communities.

PMID- 11580093
TI  - Oral health status and dental service use of adults with learning disabilities
      living in residential institutions and in the community.
AB  - OBJECTIVE: To investigate the oral health status of adults on Sheffield's
      Learning Disability Case Register, and their reported use of dental services.
      DESIGN: A short questionnaire interview of subjects with learning disabilities or
      their carers followed by a standardised epidemiological examination, by one
      trained and calibrated examiner. SETTING: Residential homes, day centres or
      community homes of people with learning disabilities in Sheffield. SUBJECTS: A
      20% random sample of adults (18-65 years) on the register. RESULTS: A response
      rate of 209 (67%) was achieved, 62% (n=130) of whom were living in the community.
      People living in residential care were significantly older (43.2 years) than
      those based in the community (36.3 years) (P<0.05). Both groups had similar mean
      DMFT scores; however, adults living in the community had significantly more
      untreated decay (DT = 1.6) and poorer oral hygiene than their counterparts in
      residential care (DT = 0.7). Adults in residential care had significantly more
      missing teeth (MT = 10.1) than those in community care (MT = 7.5). General and
      community dental services were the main providers of dental care. Subjects living
      in the community were significantly less likely to have a dentist and to use
      community dental services than their residential counterparts; they were more
      likely to attend only when having trouble. CONCLUSIONS: Adults with learning
      disabilities living in the community have greater unmet oral health needs than
      their residential counterparts and are less likely to have regular contact with
      dental services. Commissioners and providers of dental services have a
      responsibility to ensure that the health of adults with learning disabilities is
      not compromised by 'normalisation'.

PMID- 11580094
TI  - Levels of career satisfaction amongst dental healthcare professionals: comparison
      of dental therapists, dental hygienists and dental practitioners.
AB  - OBJECTIVE: To compare the levels of career satisfaction expressed by three
      professional groups working in dental health: dental therapists, dental
      hygienists and dental practitioners. BASIC RESEARCH DESIGN: Level of career
      satisfaction was assessed using a ten point scale in three surveys. Postal
      surveys were conducted of all dental therapists and dental hygienists registered
      with the General Dental Council. Data for dental practitioners were collected as
      part of the British Dental Association Omnibus Survey 2000. PARTICIPANTS: Data
      are reported for 227 dental therapists, 2,251 dental hygienists and 970 dental
      practitioners. RESULTS: Significant differences were found between groups in the
      level of career satisfaction expressed. Dental practitioners were less likely to
      express high levels of satisfaction in comparison with the other two professional
      groups. Within each group characteristics of the respondents were associated with
      satisfaction levels. Younger dental therapists and dental hygienists expressed
      lower levels of career satisfaction. The level of career satisfaction expressed
      by dental practitioners was associated with gender, place of work (North vs South
      UK), year of qualification, size of practice and system of remuneration.
      CONCLUSIONS: Dental practitioners express lower levels of job satisfaction in
      comparison to other groups of dental health care professionals. Job
      dissatisfaction among dental practitioners is related to a number of socio
      demographic factors.

PMID- 11580095
TI  - Orthodontic treatment need in Jordanian school children.
AB  - OBJECTIVE: To assess the need for orthodontic treatment among Jordanian school
      children. RESEARCH DESIGN: The vehicle of this study was the dental health
      component (DHC) of the index of orthodontic treatment need (IOTN). The
      examinations were carried out using mouth mirrors and stainless steel rulers. No
      more than 30 school children were examined at one time to prevent examiner
      fatigue. SETTING: Clinical examinations were carried out on the school premises
      under natural lighting. PARTICIPANTS: 320 10th grade school children aged 14 to
      17 years were selected at random to represent the four main areas of Amman as
      divided by the Ministry of Education in Jordan. MAIN OUTCOME MEASURES: A
      'definite need' for orthodontic treatment was recorded if the patient fell into
      grades four and five of the IOTN, while grade 3 represented 'borderline need' and
      grades 2 and 1 'no need' for treatment. RESULTS: A 'definite need' for treatment
      was recorded in 28% of children and 22% had 'border line' need on dental health
      grounds. Three main occlusal features were responsible for allocating children
      into the former category; severe displacements of more than 4 mm (45%), increased
      overjet of greater than 6 mm but less than or equal to 9 mm (22%) and impeded
      eruption of teeth (24%). CONCLUSIONS: This study has shown that 28% of Amman
      school children were in need of orthodontic treatment for dental health reasons.

PMID- 11580096
TI  - Dental caries experience of disabled children and young adults in Kuwait.
AB  - OBJECTIVE: The aim of the study was to assess the caries experience of disabled
      children and young adults in Kuwait, to set baseline data, and to determine their
      treatment need. METHOD: Dental caries was scored by surface in accordance with
      WHO criteria. The study population comprised 832 disabled children and young
      adults (3-29 years; mean age 12.1 years) who were visually impaired, hearing
      impaired, had physical handicaps or developmental disorders, attending special
      needs schools. RESULTS: The proportion of caries free subjects in the primary
      dentition (3-12-year-old children) was 11.2%. The mean dmft was 5.4, and dmfs
      15.2, being highest in the Down's syndrome and lowest in the blind. The
      proportion of caries-free subjects in permanent dentition, over 5 years of age
      was 24.2%. The smallest percentage of caries-free subjects was found in the
      hearing impaired (16.4%) and highest percentage in the blind (35.5%). The mean
      DMFT was 4.5 and the DMFS 8.7, being highest in the Down's syndrome and lowest in
      the blind. Prevalence of untreated decay was highest in hearing impaired (86%).
      The caries experience of first permanent molars represented the largest
      proportion of the DMFT score (53.6%). In the permanent dentition increasing age,
      impaired hearing, and poor oral hygiene were significantly associated with caries
      risk. CONCLUSIONS: Caries experience among this disabled population was clearly
      higher than among the respective age groups in a previous national population
      survey. The study confirmed the need for strengthening organised preventive and
      restorative care for this population in Kuwait.

PMID- 11580097
TI  - CD5 (OKT1) augments CD3-mediated intracellular signaling events in human T
      lymphocytes.
AB  - CD5 is expressed on thymocytes, all mature T cells, and a subset of mature B
      cells, and probably contributes to T-cell-B-cell adhesion. We assessed whether
      CD5-crosslinking by mAb augments T-cell stimulation. Plate-bound anti-CD5 or anti
      CD3 mAb alone had no effect on any of the assessed activation parameters of
      resting T cells. However, concomitant signaling through both CD5 and CD3 by plate
      bound antibodies resulted in marked increases in T-cell surface CD69 expression
      and T-cell metabolism, as assessed by the T cell's ability to reduce 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxylmethoxyphenyl)-2-(4-sulphophenyl)-2H
      tetrazolium (MTS) to formazen. In addition, simultaneous cross-linking of CD5 and
      CD3 caused a significant (p < 0.001) increase in phosphatidylinositol hydrolysis
      in resting T cells compared to stimulation with anti-CD3 mAb alone or anti-CD3
      mAb plus anti-CD5 isotype control antibody. These results indicate that CD5
      augments signaling through CD3 and consequently functions as a costimulatory
      molecule for resting T cells.

PMID- 11580098
TI  - Induction of nitric oxide synthesis by probiotic Lactobacillus rhamnosus GG in
      J774 macrophages and human T84 intestinal epithelial cells.
AB  - BACKGROUNDS AND AIMS: Probiotic Lactobacillus rhamnosus GG (LGG) has proved to be
      beneficial in the treatment of viral- and antibiotic-associated diarrhea but the
      mechanisms of action remain unknown. Nitric oxide (NO) is involved in the
      protective mechanisms in the gastrointestinal tract and may contribute to some of
      the beneficial effects of probiotics. The aim of the present study was to
      investigate if induction of NO synthesis is involved in the cellular actions of
      LGG. METHODS: NO synthesis and its regulation were measured in cultures of J774
      murine macrophages and human T84 colon epithelial cells. NO production was
      measured as its metabolite nitrite accumulated into the culture medium. Inducible
      nitric oxide synthase (iNOS) protein and iNOS mRNA were detected by Western blot
      and RT-PCR, respectively. RESULTS: In J774 macrophages, LGG induced a low level
      production of NO in the presence of gamma interferon (IFNgamma) and it was
      inhibited by NOS inhibitors, cycloheximide and by a NF-kappa B inhibitor
      pyrrolidinedithiocarbamate. Accordingly, LGG and IFNgamma-stimulation increased
      iNOS mRNA and protein levels. T84 cells produced NO in response to LGG when first
      primed with a combination of IL-1beta, TNFalpha and IFNgamma. Lipoteichoic acid
      (LA), an antigenic structure in gram-positive bacteria, also induced NO formation
      in J774 cells in the presence of IFNgamma suggesting that LA may be the active
      component in LGG. CONCLUSIONS: LGG induces NO production in J774 macrophages and
      in human T84 colon epithelial cells through induction of iNOS by a mechanism
      involving activation of transcription factor NF-kappaB. Induction of iNOS and low
      level synthesis of NO may be involved in the protective actions of LGG in the
      gastrointestinal tract.

PMID- 11580099
TI  - Interaction between the antinociceptive effect of ketoprofen and adrenergic
      modulatory systems.
AB  - The interaction between the antinociceptive activity of ketoprofen and adrenergic
      agents was evaluated in the writhing test of mice. Dose-response curves were
      obtained for systemic and intrathecal antinociceptive effects of ketoprofen,
      phenylephrine, clonidine, desipramine, and prazosin; and ED50 were calculated.
      The interactions were evaluated by isobolographic analysis of the systemic or
      intrathecal co-administration of fixed-ratio combinations of ketoprofen with each
      adrenergic agent. The intraperitoneal combinations of ketoprofen with
      phenylephrine, clonidine, and prazosin showed supra-additivity, indicating that
      activation of alpha1 and alpha2 adrenoceptors play a role in nociceptive
      transmission at supraspinal levels. The same combinations given intrathecal were
      only additive. Desipramine intraperitoneal was also supra-additive: however, when
      ketoprofen was administered intrathecally with desipramine, only an additive
      interaction was obtained. The supra-additive interactions suggest that
      complementary mechanisms of antinociception have been activated, related with
      interference with the multiplicity of receptors and systems involved in the
      transmission of the nociceptive information. Racemic ketoprofen has an
      antinociceptive activity which is probably not only due to COX inhibition but
      also involves noradrenergic systems at spinal and supraspinal levels.

PMID- 11580100
TI  - Cell-cell contacts with epithelial cells modulate the phenotype of human
      macrophages.
AB  - Interactions of macrophages with epithelium represent one of the pathways
      involved in regulating local immune mechanisms. We studied the effect of cell
      cell contact with an epithelial monolayer on the phenotype of macrophages. Human
      monocytes and THP-1 macrophages were co-cultured with monolayers of human
      bronchial epithelial cells (HBECs), the alveolar type II-like cell line A549,
      renal adenocarcinoma epithelial cells (RA), and the lung fibroblast strain HFL-1.
      The expression of CD11b, CD14, CD54, and HLA-DR was measured by
      immunocytochemistry and flow cytometry and showed epithelial cell induction of
      CD54 and HLA-DR in monocytes and of all antigens in THP-1 cells. Co-culture with
      fibroblasts did not change the phenotype of macrophages. Separation by a filter
      insert inhibited most of the effects. Culture supernatants did not induce
      prominent phenotypic changes. Cell-cell contacts with epithelium appear to be of
      importance in regulating the phenotype of macrophages.

PMID- 11580101
TI  - Nitric oxide mediates the inhibition of neutrophil migration induced by systemic
      administration of LPS.
AB  - To investigate the role of NO in the inhibition of neutrophil migration by
      circulating endotoxin, mice were pretreated with NO synthase inhibitors or with a
      free radical scavenger (D-penicillamine), before intravenous LPS injection. LPS
      dose-dependently inhibited the thioglycollate-induced neutrophil migration into
      the peritoneal cavities. Aminoguanidine, a selective inducible NO synthase
      inhibitor, abolished the inhibition of neutrophil migration and the increase in
      serum nitrate levels induced by a nonlethal dose of LPS. During lethal
      endotoxemia aminoguanidine partially abolished the neutrophil migration
      inhibition. Additionally, D-penicillamine prevented the inhibition of neutrophil
      migration caused by LPS. However, Nitro-L-Arginine, a selective constitutive NO
      synthase inhibitor, did not prevent neutrophil migration inhibition.
      Aminoguanidine treatment did not affect the systemic increased levels of TNF
      alpha, IL-1beta, and IL-10, suggesting that NO is the final mediator involved in
      the inhibition of neutrophil migration. Our results suggest that NO released by
      the inducible NO synthase mediates the inhibition of neutrophil migration
      mediated by circulating LPS.

PMID- 11580102
TI  - Identification and cloning of the SNARE proteins VAMP-2 and syntaxin-4 from HL-60
      cells and human neutrophils.
AB  - Degranulation and membrane fusion by neutrophils are essential to host defense.
      We sought homologues of neuron-specific fusion proteins in human neutrophils and
      in their precursors, the promyelocytic cell line HL-60. We screened a
      differentiated HL-60 library and obtained an 848 bp sequence with a 351 bp open
      reading frame, identical to that published for human VAMP-2 and including 5' and
      3' untranslated regions. RNA from HL-60 cells during differentiation into the
      neutrophil lineage was subjected to Northern blot analysis. which revealed a
      transcript of approximately 1050 bp at all stages of differentiation. The amount
      of these transcripts increased approximately threefold during differentiation, a
      finding confirmed by quantitative RT-PCR. We also detected mRNA for VAMP-2 in
      human neutrophils and monocytes using RT-PCR. In like fashion, transcripts of
      syntaxin-4, another fusion protein, were recovered from a neutrophil cDNA
      library. As with VAMP-2, expression of syntaxin-4 (determined by Northern blots)
      also increased, but by only 50%, during differentiation of HL-60 cells. These
      studies demonstrate that neutrophils and their progenitors possess mRNA for the
      fusion proteins VAMP-2 and syntaxin-4, and that their transcription increases
      during differentiation, concurrent with the functional maturation of myeloid
      cells.

PMID- 11580104
TI  - Complex systems analysis: a tool for shock research.
AB  - For the past century, students of shock have focused research efforts to
      illuminate specific mechanisms that cause, or fail as a consequence of,
      circulatory collapse. Although clinical strategies aimed at supporting or
      restoring individual organ systems have proven effective, many patients succumb
      to more generalized multiple organ system failure. We suggest that general
      biological systems failure cannot be interpreted through reliance on reductionist
      science. We propose that complex systems analysis is an essential tool for shock
      research and we evaluate its application to genomic technologies.

PMID- 11580103
TI  - Morphine-6beta-glucuronide modulates the expression of inducible nitric oxide
      synthase.
AB  - The immunomodulatory effects of morphine are well established; however,
      suprisingly little is known about the immunomodulatory properties of the major
      metabolites of morphine. The present study tests the hypothesis that expression
      of inducible nitric oxide synthase (iNOS) is modulated by the administration of
      the morphine metabolite, morphine-6beta-glucuronide. The initial study using rats
      shows that morphine-6beta-glucuronide administration (0, 1.0, 3.163, 10 mg/kg
      s.c.) results in a pronounced reduction in lipopolysaccharide (LPS)-induced
      expression of iNOS (inducible nitricoxide synthease) in spleen, lung, and liver
      tissue as measured by western blotting. Morphine-6beta-glucuronide also produces
      a reduction in the level of plasma nitrite/nitrate, the more stable end-product
      of nitric oxide degradation. In a subsequent study, administration of the opioid
      receptor antagonist, naltrexone (0.1 mg/kg) prior to the injection of morphine
      6beta-glucuronide (10 mg/kg) blocks the morphine-6beta-glucuronide induced
      reduction of iNOS expression and plasma nitrite/nitrite levels indicating that
      the effect is mediated via the opioid-receptor. This study provides the first
      evidence that morphine-6beta-glucuronide alters the expression of iNOS.

PMID- 11580105
TI  - Complexity and non-linearity in shock research: reductionism or synthesis?
AB  - The various analytical techniques used to explain the many supposed mediators of
      sepsis and septic shock have outpaced the integrative approaches that simplify
      this complexity for the physiologist and the clinician. In this article we
      discuss the pros and cons of reductionism and its limitations in the field of
      shock research and emphasize the need for synthesis research. Taking account of
      the historical development of natural science, we will discuss the question of
      how far a reductionist approach can help to explain biological phenomena and
      conclude that reductionism, although essential to the scientific process, reduces
      the evidence absurdity if exaggerated. The part is never the whole, and it is
      impossible to understand the whole through limited dissections of its parts. The
      understanding of complex systems requires approaches other than those of
      explanatory reductionism. We emphasize a different approach-systems thinking.
      Systems scientists are not interested in the underlying components; they describe
      and characterize complex relations. Other disciplines that use systems thinking
      should be studied. However, to follow the concept of synthesis, reductionists
      must describe the components of the system. Reductionism and synthesis are
      therefore the two sides of a coin. Professional synthesis research is a serious
      challenge in shock research.

PMID- 11580106
TI  - Gene expression in intestinal epithelial cells, IEC-6, is altered by burn injury
      induced circulating factors.
AB  - Severe burn injury is commonly associated with significant changes in intestinal
      epithelial function. These changes include mucosal atrophy and increased
      permeability. To date, the mechanism by which burn injury alters intestinal
      epithelium function are not clear. We used an in vitro model of intestinal
      epithelium, IEC-6 cells, and observed that the integrity of confluent culture is
      disrupted and cell growth and migration rates are reduced in the presence of
      serum collected from scald burn injury rats (SRS) (6). To identify gene products
      involved in mechanisms underlying these effects, we used the cDNA expression
      microarray analysis and found that genes whose expression was affected by SRS in
      IEC-6 cells were primarily associated with cell shape, growth and death, stress
      response, protein turnover and transport of water and electrolytes. These data
      demonstrate that a burn-induced circulating factor(s) modulates expression of
      genes, which may affect intestinal epithelial cell survival and function. Thus,
      these findings provide clues to the nature of molecular mechanisms potentially
      involved in multiple-organ malfunction, in particular the atrophy and enhanced
      permeability of gut mucosa, after burn injury.

PMID- 11580107
TI  - microArRAY of hope.

PMID- 11580108
TI  - Agent-based computer simulation and sirs: building a bridge between basic science
      and clinical trials.
AB  - The management of Systemic Inflammatory Response Syndrome (SIRS)/Multiple Organ
      Failure (MOF) remains the greatest challenge in the field of critical care. There
      has been uniform difficulty in translating the results of basic science research
      into effective therapeutic regimes. We propose that this is due in part to a
      failure to account for the complex, nonlinear nature of the inflammatory process
      of which SIRS/MOF represents a disordered state. Attempts to manipulate this
      process without an understanding of the dynamics of the system may potentially
      produce unintended consequences. Agent-Based Computer Simulation (ABCS) provides
      a means to synthesize the information acquired from the linear analysis of basic
      science into a model that preserves the complexity of the inflammatory system. We
      have constructed an abstracted version of the inflammatory process using an ABCS
      that is based at the cellular level. Despite its abstraction, the simulation
      produces non-linear behavior and reproduces the dynamic structure of the
      inflammatory response. Furthermore, adjustment of the simulation to model one of
      the unsuccessful initial anti-inflammatory trials of the 1990's demonstrates the
      adverse outcome that was observed in those clinical trials. It must be emphasized
      that the current model is extremely abstract and simplified. However, it is hoped
      that future ABCSs of sufficient sophistication eventually may provide an
      important bridging tool to translate basic science discoveries into clinical
      applications. Creating these simulations will require a large collaborative
      effort, and it is hoped that this paper will stimulate interest in this form of
      analysis.

PMID- 11580109
TI  - Uncoupling and recoupling of autonomic regulation of the heart beat in pediatric
      septic shock.
AB  - Healthy physiological systems exhibit marked signal variability and complexity,
      whereas diseased systems generally show a loss of variability, decreased
      complexity ("decomplexification"), and increased regularity. The goal of this
      study was to evaluate the uncoupling and recoupling phenomenon in children with
      septic shock by observing serial changes in heart rate variability metrics. Data
      were collected from 7 children with septic shock by using the computer system in
      the Complex Systems Laboratory at Oregon Health Sciences University. Heart rate
      time series were constructed and analyzed by using the Hales Research System at
      intervals of 6 h during pediatric intensive care unit (PICU) hospitalization.
      These power spectral values were then plotted vs. time. Six of seven patients
      showed an increase over time in low-frequency heart rate power and the low-/high
      frequency ratio, whereas high-frequency heart rate power decreased. We also
      compared the change in mean heart rate, heart rate standard deviation, and power
      spectral values during the first 24 h of PICU hospitalization vs. the remainder
      of the PICU stay (for the 5 patients with a PICU length of stay > 48 h). Compared
      to the initial 24 h in the PICU, low-frequency power and the low-/high-frequency
      ratio increased, whereas high-frequency power decreased over the course of the
      illness. This report shows the potential value of monitoring the uncoupling and
      recoupling phenomenon in patients with septic shock. Our results are in agreement
      with other investigators who report evidence of decomplexification both in
      experimental models of sepsis and in clinical studies and provide direction for
      further work.

PMID- 11580110
TI  - Shock at the millennium II. Walter B. Cannon and Lawrence J. Henderson.
AB  - Walter B. Cannon and Lawrence J. Henderson, students of shock in the early
      twentieth century, were contemporaries for four decades in the Harvard Department
      of Physiology. While their discoveries continue to have important clinical
      applications, both men established complementary methods of scientific
      investigation and description. Both men were inspired by Claude Bernard, hewing
      to his principle of the stability of the milieu interieur. Cannon, the
      traditional experimentalist, employed a reductionist approach by holding constant
      the confounding variables of his experiments; in contrast, Henderson, the
      strategist of theoretical analysis, deduced patterns and relationships from less
      constrained models, focusing on complexity using mathematics and graphs. In
      delineation, Cannon described mechanisms; Henderson described the organization of
      systems. Cannon's emphasis on homeostasis with the identification of feedback
      arcs dominated shock research for the balance of the twentieth century.
      Henderson's perspective designating the importance of organization to those
      restorative mechanisms could well reemerge to dominate the twenty-first.

PMID- 11580111
TI  - Hypertonic saline activation of p38 MAPK primes the PMN respiratory burst.
AB  - Investigation of hypertonic saline (HTS) modulation of neutrophils (PMN)
      cytotoxic responses has generated seemingly contradictory results. Clinically
      relevant levels of HTS attenuate receptor-mediated p38 MAPK signaling, whereas
      higher levels activate p38 MAPK. Concurrently, HTS exerts a dose-dependent
      attenuation of the PMN respiratory burst, most notably at concentrations where
      p38 MAPK is activated. We hypothesized that HTS-mediated p38 MAPK activation
      augments the PMN respiratory burst on return to normotonicity. We found that
      although clinically relevant levels of HTS (Na+ > or = 200 mM) did not activate
      p38 MAPK, higher concentrations (Na+ > or = 300 mM) resulted in activation
      comparable with that after PAF stimulation. Transient stimulation with high
      levels of HTS primed the PMN respiratory burst in response to fMLP and PMA. This
      effect was attenuated by pretreatment with SB 203580, a p38 MAPK specific
      inhibitor. We conclude that severe osmotic shock primes the respiratory burst via
      p38 MAPK signaling, further supporting the role of this signaling cascade in PMN
      priming.

PMID- 11580112
TI  - Mesenteric lymph from rats subjected to trauma-hemorrhagic shock are injurious to
      rat pulmonary microvascular endothelial cells as well as human umbilical vein
      endothelial cells.
AB  - Previously, we have documented that gut-derived lymph from rats subjected to
      trauma/hemorrhagic shock (T/HS) is injurious to human umbilical vein endothelial
      cells (HUVEC). To verify these findings in an all rat systems, the ability of
      T/HS lymph to increase rat pulmonary microvascular endothelial cell (RPMVEC)
      monolayer permeability and kill RPMVEC was compared with that observed with
      HUVECs. RPMVEcs isolated from male rats or HUVECs were grown in 24-well plates
      for the cytotoxicity assays or on permeable filters in a two-chamber system for
      permeability assays. Mesenteric lymph was collected from male rats subjected to
      trauma (laparotomy) plus hemorrhagic shock (T/HS group) or to a laparotomy plus
      sham-shock (T/SS group). The T/HS group had their mean arterial pressure
      decreased to 30 mmHg and kept there for 90 min. Lymph samples centrifuged to
      remove the cellular component were incubated with the RPMVECs or HUVECs at a 10%
      concentration. Neither T/SS lymph nor post-T/HS portal vein plasma was toxic to
      or increased the permeability of the RPMVECs or HUVECs. The pattern of
      cytotoxicity observed in the HUVECs incubated with T/HS mesenteric lymph was
      similar to that observed in the RPMVECs, as reflected by trypan blue dye
      exclusion, with more than 95% of the HUVECs and RPMVECs being killed after a 16-h
      incubation with T/HS mesenteric lymph. However, at earlier time points the amount
      of LDH released from the HUVEC cells incubated with T/HS lymph was greater than
      that observed with the PRMVEC, although trypan blue dye exclusion was similar.
      Similarly, incubation with 10% T/HS lymph increased the permeability of both
      HUVEC and RPMVEC monolayers more than 2-fold, even with an incubation period as
      short as 1 h. In conclusion, these results provide further evidence that T/HS
      lymph, but not T/SS lymph or post-T/HS portal vein plasma, is injurious to
      endothelial cells and that RPMVECs are as susceptible to injury as HUVECs.
      Additionally, these studies support the emerging concept that gut-induced distant
      organ injury is mediated by factors contained in mesenteric lymph.

PMID- 11580113
TI  - Reversible temperature-sensitive alterations in lung fluid balance.
AB  - Hypothermia is intentionally imposed during the harvesting of lungs for
      transplantation. The aim of this study was to investigate the fluid balance
      alterations in rat lung preparations exposed to hypothermic perfusion. Lowering
      perfusate temperature from 37 degrees C to values between 27 and 7 degrees C
      caused an immediate, marked pulmonary hypertension and vasoconstriction
      accompanied by rapid development of pulmonary edema (+1.15 g, or approximately
      90%, gain in lung weight within 5 min). However, on rewarming, vasoconstriction
      was immediately reversed. Edema was resolved, but along a two-component time
      course: an immediate reduction of lung weight on rewarming (t 1/2 of 0.5 min)
      that mirrored the recovery of pulmonary artery pressure and vasoconstriction, and
      also a slower pressure-independent component of recovery (t 1/2 of 3.5 min).
      Ouabain (300 microM) markedly inhibited the lung's ability to recover from edema,
      indicating that fluid clearance from lung tissue was the result of activation of
      ouabain-sensitive (Na+,K+)-ATPase pump. Results could not be explained by
      vascular or airspace injury as lung sections from hypothermic lungs appeared
      normal. The findings indicate that hypothermia induces pulmonary edema formation,
      which can be rapidly cleared upon rewarming by activation of ouabain-sensitive
      (Na+,K+)-ATPase pump. Thus, impaired fluid clearance from lung extravascular
      spaces may be a critical factor limiting gas exchange in transplanted lungs
      exposed to hypothermia.

PMID- 11580114
TI  - The involvement of multiple protease-antiprotease systems and gut origin sepsis
      in zymosan-associated endothelial barrier injury and multiple organ dysfunction
      in rats.
AB  - Multiple organ dysfunction syndrome is a dominant cause of mortality in the
      intensive care unit. Experimentally, a condition similar to the multiple organ
      dysfunction syndrome can be induced by the intraperitoneal injection of sterile
      zymosan. In the present study we investigate potential alterations in multiple
      organ functions, endothelial permeability, and antiproteinases after
      intraperitoneal injection of zymosan at various doses. Zymosan-induced
      generalized inflammation lead to endothelial barrier injury in multiple
      organs/tissues, a decrease in systemic arterial pressure, impaired organ function
      and gut defence function, and consumption of protease inhibitors, particularly
      the consumption of alpha2 antiplasmin. Endothelial barrier injury appears to
      present a dose- and organ-dependent pattern in multiple organs/tissues, and the
      increase in endothelial barrier permeability occurred prior to organ dysfunction.
      Zymosan induced the development of multiple organ dysfunction syndrome, probably
      initiating multiple protease-antiprotease systems, particularly the fibrinolytic
      system, leading to endothelial barrier injury, tissue edema, parenchymal cell
      damage, and eventual organ dysfunction, potentially augmented by a secondary
      bacterial infection.

PMID- 11580115
TI  - Presence of nitrotyrosine with minimal inducible nitric oxide synthase induction
      in lipopolysaccharide-treated pigs.
AB  - The production of large amounts of nitric oxide (NO) by the inducible form of
      nitric oxide synthase (iNOS) and the subsequent production of peroxynitrite (OONO
      ) are believed to be major factors in the hemodynamic abnormalities of sepsis.
      This finding is based on data from rats and mice but has not been established in
      other species. Therefore, we examined the role of iNOS in lipopolysaccharide
      (LPS)-treated pigs, which have a hemodynamic pattern with sepsis that is more
      similar to humans than rats. Pigs were anesthetized, ventilated, and given LPS (n
      = 12), 20 microg/kg over 2 h, or saline (n = 7). They were killed after 2 (n = 8
      LPS, 7 control) or 4 h (4 LPS). We measured cardiac output (CO), mean arterial
      (Part), and pulmonary and central venous pressures. We evaluated NO production by
      measuring expired NO, and plasma nitrate/nitrite concentration, NOS activity (in
      lung tissue), and iNOS protein by Western analysis, and immunohistochemistry
      (lung and liver), as well as iNOS mRNA by Northern analysis (liver and lung). We
      also measured nitrotyrosine as evidence of OONO- production by slot blot, Western
      analysis, and immunohistochemistry. By 2 h, Part fell and CO did not change so
      that systemic vascular resistance decreased from 21.5+/-2.9 to 12.7+/-3.1 mmHg x
      L(-1) x min (P < 0.05) and remained at 11.3+/-1.7 mmHg x L(-1) x min in the
      animals observed for 4 h. Plasma nitrate/nitrite, expired NO, and NOS activity
      did not change. We found no iNOS in tissues by Western analysis with 5 different
      antibodies but detected a small amount of iNOS by immunohistochemistry in
      inflammatory cells and small vessels. There was a small increase in iNOS mRNA in
      liver and lung. Despite the minimal increase in iNOS, nitrotyrosine was increased
      in small vessels and in inflammatory cells. In conclusion, caution should be used
      when extrapolating the septic response in rodents to other species, for the
      pattern of iNOS induction is very different.

PMID- 11580116
TI  - Lung and liver injury following hepatic ischemia/reperfusion in the rat is
      increased by exogenous lipopolysaccharide which also increases hepatic TNF
      production in vivo and in vitro.
AB  - Hepatic ischemia/reperfusion (I/R) results in tumor necrosis factor (TNF)
      release. Kupffer cells (KC) are one source of this TNF. This study investigates
      the effects of hepatic I/R combined with lipopolysaccharide (LPS) on the lung and
      liver injury that follow hepatic I/R and on hepatic release of TNF, epithelial
      neutrophil activating protein (ENA-78), and macrophage inflammatory protein-2
      (MIP-2). The effects of these experimental conditions on TNF production by
      primary rat KC in vitro were also investigated. Rats were subjected to hepatic
      I/R alone, hepatic I/R + LPS, sham laparotomy alone, or sham laparotomy + LPS and
      pulmonary MPO, pulmonary microvascular permeability, hepatic neutrophil influx,
      hepatic injury, and hepatic TNF, ENA-78, and MIP-2 production were measured.
      These experiments demonstrated that hepatic I/R in conjunction with LPS results
      in a more severe lung and liver injury and increased hepatic TNF, ENA-78, and MIP
      2 release. The effects of these experimental conditions on rat KC TNF production
      demonstrated that hepatic I/R + LPS results in a more significant release of TNF
      as compared to LPS alone or I/R alone. Hepatic I/R plus LPS results in a more
      severe lung and liver injury and is likely secondary to a more significant and
      prolonged release of TNF by KC. This may provide a mechanism for development of
      multiple organ system failure in some patients undergoing hepatic resection,
      hepatic transplantation, complex vascular operations, or in the setting of
      hypovolemic shock. Portal endotoxemia related to mesenteric venous congestion or
      other systemic insults may have a significant impact on post-operative
      complications and recovery in the setting of a local or global hepatic I/R
      injury.

PMID- 11580117
TI  - Regional distribution of endothelin-1 and endothelin converting enzyme-1 in
      porcine endotoxemia.
AB  - Endothelin-1 (ET-1) levels are markedly increased in sepsis. Since ET-1 is
      primarily transcriptionally regulated, there should be a corresponding increase
      in pre-pro-endothelin-1 (ppET-1). Our objective was to determine whether ppET-1
      is increased in pigs with a low systemic vascular resistance. We also examined
      the distribution of ET-1 and the regulation of endothelin-converting enzyme 1
      (ECE-1), the rate limiting enzyme in ET-1 production. We anesthetized and
      ventilated 16 pigs. We measured arterial, pulmonary, and central venous
      pressures, as well as cardiac output. ET-1 was measured by radioimmunoassay in
      plasma and in multiple tissues. We infused 20 microg/kg of endotoxin over 2 h and
      then sacrificed the animals. ppET-1 and ECE-1 mRNA were assessed by Northern
      analysis. We performed immunohistochemistry for the assessment of tissue ET-1 and
      ECE-1. The systemic vascular resistance rose at 30 min, but fell by 120 min.
      Plasma ET-1 more than doubled by 2 h. However, there was no change in the
      concentration of ET-1 in any tissue except in the pulmonary artery. By
      immunohistochemistry, there was also no change in ET-1 in aorta, vena cava,
      heart, lung, liver, and kidney. Distribution of ECE-1 followed that of ET-1 on
      immunohistochemistry. There was a significant increase in ppET-1 mRNA in liver,
      kidney papillae, and vena cava, and a tendency for an increase in other tissues.
      This was paralleled by an increase in ECE-1 mRNA. In conclusion, the amount of
      ECE-1 mRNA and protein parallel those of ET-1. Endotoxemia is associated with a
      marked increase in plasma ET-1 and an increase in ppET-1 and ECE-1 mRNA in
      multiple tissues; however, there was no significant change in tissue ET-1 except
      in the pulmonary artery. The rise in plasma levels without a change in tissue
      levels suggests a greater release into the vasculature in sepsis than under
      normal conditions.

PMID- 11580118
TI  - Management of the patient after an osteoporotic fracture: Guidelines for
      orthopedic surgeons--consensus conference on Treatment of Osteoporosis for
      Orthopedic Surgeons, Nordic Orthopedic Federation, Tampere, Finland 2000.

PMID- 11580119
TI  - Perthes' disease or late avascular necrosis after developmental dislocation of
      the hip? 10 children followed for 6-35 years.
AB  - We studied 10 patients treated because of late avascular necrosis (AVN) mimicking
      Legg-Calve-Perthes' disease (LCPD) after developmental dislocation of the hip
      (DDH). DDH was recognized late at an average age of 5.4 months and in all
      children it was treated without surgery. In 4 children, the treatment was
      complicated by mild AVN of the femoral head, which had disappeared before 3 years
      of age. The first clinical signs of LCPD were noted at a mean age of 5.8 years.
      They all had Catterall's type III or IV of LCPD. The course was typical of LCPD.
      8 children were operated on at mean age of 7.4 (5-12) years. In 7 of them,
      subtrochanteric derotation-varisation osteotomy of the femur with shortening
      combined mainly with Dega's pelvic osteotomy was done. The operative treatment
      resulted in a concentric position of the femoral head and good coverage of the
      acetabulum. Follow-ups were done at 10 (6-35) years. Shortened femoral neck and
      trochanteric overgrowth occurred in 4 operated hips. According to the Stulberg
      classification, 2 hips were classified as type I, 1 as I/II, 5 as II/I as II/III
      and 1 as IV. We conclude that LCPD mimicking late AVN can occur in hips treated
      because of developmental dislocation.

PMID- 11580120
TI  - Morphologic characteristics of periprosthetic tissues from hip prostheses with
      ceramic-ceramic couples: a comparative histologic investigation of 18 revision
      and 30 autopsy cases.
AB  - Pseudocapsules and interface membranes from 18 revision cases having hip
      prostheses with ceramic-ceramic couples and 30 autopsy specimens (6 with ceramic
      ceramic couples, 7 with ceramic-polyethylene combinations and 17 with metal
      polyethylene combinations) were histomorphologically analyzed, including a
      semiquantitative grading of the wear particles and histologic changes. Unlike the
      revision cases, which usually showed ceramic wear particles in the adjacent
      tissues, only half of the autopsy cases revealed ceramic wear. As compared to the
      ceramic-polyethylene and metal-polyethylene couples, the alumina on alumina
      combinations showed a thinner synovial layer with reduced villous transformation
      and smaller infiltrates of macrophages and necroses, which can be explained by
      the absence of polyethylene wear. Metal-polyethylene couplings produced more than
      twice as many polyethylene wear particles with correspondingly more marked
      foreign body reaction than the ceramic-polyethylene couplings.

PMID- 11580121
TI  - Osteoblastic response to osteoarthrosis of the hip does not predict outcome of
      cementless cup fixation: 79 patients followed for 5-11 years.
AB  - We evaluated the influence of osteoblastic response to osteoarthrosis of the hip
      on the outcome of cementless acetabular cup after 91 total hip replacements in 79
      patients. Of the 91 hips, 23 were atrophic, 37 normotrophic, and 31 hypertrophic,
      according to Bombelli's criteria. There were no clinical or radiographic
      differences among the three groups at the final follow-up (average 7 (5-11)
      years), when stable bone growth had been achieved by all of the acetabular cups
      in patients with the atrophic type, 35/37 of the normotrophic type, and all the
      hypertrophic type. Revision of the acetabular cup was performed on 1 hip of the
      normotrophic type, in connection with severe polyethylene liner wear and
      progressive osteolysis.

PMID- 11580122
TI  - Clinical and radiographic outcome of femoral head fractures: 30 patients followed
      for 3-10 years.
AB  - The aim of this study was to evaluate the outcome of 30 femoral head fractures.
      We modified Pipkin's classification into 4 types: I (5 cases) small fracture of
      head distal to fovea centralis, which was too small or too fragmented to be fixed
      with screws; II (18 cases), larger fracture of head distal to fovea centralis;
      III (4 cases), large fracture of head proximal to fovea centralis, and IV (3
      cases), comminuted fracture of head. Excision of the head fragment was done in
      all 5 cases of type I and in 9 type II fractures. Fixation of the head fragment
      was performed in 9 type II and in all 4 type III cases. The femoral head was
      replaced in all 3 type IV fractures. After a mean follow-up of 3-10 years, the
      clinical outcome, according to Epstein et al.'s critieria, were excellent in 7,
      good in 15, fair in 4 and poor in 1, except in type IV, and the radiographic
      outcome was excellent in 15, good in 7, fair in 4 and poor in 1. On the basis of
      our findings, we conclude that excision of the small fragment is a good choice of
      treatment in type 1. Early accurate reduction with stable internal fixation in
      type II or III permits bony union. Arthroplasty seems to be indicated in type IV.

PMID- 11580123
TI  - Posterolateral spinal fusion at unintended levels due to bone-graft migration: no
      effect on clinical outcome in 19/130 patients.
AB  - In a prospective randomized study, we evaluated the risk of lumbar posterolateral
      spinal fusion at an unintended level due to bone graft migration. 130 patients
      underwent fusion supplemented by pedicle screw fixation (Cotrell-Dubousset, 64
      patients) or uninstrumented fusion (66 patients). This was assessed by two
      independent observers on antero-posterior, and lateral radiographs taken 1 year
      after surgery. All patients had ben operated on at the preoperatively planned
      levels. Both observers agreed that fusion had taken place at an unintended level
      in 19 cases (14%). We found a tendency towards a higher risk of this
      "complication" when using supplementary pedicle screw fixation. The functional
      outcome, assessed by the Dallas Pain Questionnaire and the Low Back Pain Rating
      scale, was similar in patients having fusion at an unintended level and in
      patients fused only at the intended levels. There was no difference between the
      two groups concerning reoperation rates, postoperative smoking or social status.
      We conclude that unintended fusion occurs and tends to be commoner with the use
      of pedicle screw instrumentation. However, this complication seems not to affect
      the functional outcome if fusion has taken place at the intended level.

PMID- 11580124
TI  - Reconstruction of posttraumatic long bone defect with free vascularized bone
      graft: good outcome in 48 patients with 6 years' follow-up.
AB  - We analyzed our clinical results in 48 patients (40 men) treated during 1990-1993
      with free vascularized bone-graft reconstruction for bone defects, the follow-up
      being an average 6 (5-8) years. The bone defects were located in the femur (10),
      tibia (32), humerus (2), and forearm (4). We performed 41 fibula transfers, 4
      iliac transfers, and 3 rib transfers in these patients. 3 patients required early
      revision surgery due to venous thrombosis. The average time needed for
      radiographic bone union was 4.2 months. Bone transfers to the lower extremity
      showed significantly more hypertrophy than those in the upper extremity. The
      functional outcome was good in 43 patients.

PMID- 11580125
TI  - The epidemiology of proximal humeral fractures.
AB  - We present a 5-year prospective study of the epidemiology of 1,027 proximal
      humeral fractures. These fractures, which tend to occur in fit elderly persons,
      have a unipolar age distribution and the highest age-specific incidence occurs in
      women between 80 and 89 years of age. The commonest was the B1.1 impacted valgus
      fracture, found in one-fifth of the cases in this series, a type that is not
      included in the Neer classification. We used both Neer and AO classifications.
      The AO classification proved to be more comprehensive because in the Neer
      classification, half of the fractures are minimally displaced and almost nine
      tenths fall into only three categories. In the AO classification, the B1.1, A2.2,
      A3.2 and A1.2 sub-groups comprise over half of all proximal humeral fractures,
      while the AO type C fractures occur in only 6%. We suggest that the literature
      does not adequately reflect the spectrum of proximal humeral fractures.

PMID- 11580126
TI  - Kinematics after tear in the anterior cruciate ligament: dynamic bilateral
      radiostereometric studies in 11 patients.
AB  - We studied the kinematics of both knees using radiostereometry in 11 patients
      with unilateral injury of the anterior cruciate ligament and normal contralateral
      knee. Continuous radiostereometric exposures at a speed of 24 exposures a second
      were performed, when the patients ascended an 8 cm high platform. The tibial
      center was more dorsally displaced and the tibia more externally rotated on the
      injured side. This increasing external tibial rotation was associated with
      increased anterior displacement of the lateral femoral condyle. The latter also
      displayed less anterior-posterior translations during continuous extension. The
      anterior-posterior translation of the medial condyle was about the same as on the
      uninjured side. Changes in the kinematics of the knee joint due to rupture of the
      anterior cruciate ligament can result in an abnormal joint load, which may
      increase the risk of damage to the cartilage and the menisci.

PMID- 11580127
TI  - The semitendinosus tendon regenerates after resection: a morphologic and MRI
      analysis in 6 patients after resection for anterior cruciate ligament
      reconstruction.
AB  - Recently, the surprising observation has been made, supported by clinical and MRI
      findings, that the semitendinosus tendon can regenerate after being harvested in
      its whole length and thickness for anterior cruciate ligament reconstruction. We
      studied 6 patients with previous anterior cruciate ligament reconstruction, using
      a quadruple semitendinosus tendon autograft. In 5 of these, physical examination
      and MRI showed that the tendond had regenerated. In all 6 patients, the findings
      were documented macroscopically by open surgical exploration and in the 5
      regenerated tendons, also morphologically by biopsies. Macroscopically,
      histologically and immunohistochemically the regenerated tendons closely
      resembled normal ones with focal scar-like areas. Our present findings and
      earlier studies show that full length and thickness harvesting of the
      semitendinosus tendon in most cases result in full-length tendon regeneration
      with tissue closely resembling the normal tendon.

PMID- 11580128
TI  - Predictors of outcome of floating knee injuries in adults: 89 patients followed
      for 2-12 years.
AB  - Of the 98 floating knee injuries that were consecutively treated from 1987 to
      1997, 89 patients were available for analysis. There were 80 males and 9 females,
      ranging from 15 to 70 years old. Average follow-up was 5 (2-12) years. Injury
      severity scores ranged from 18 to 45. 21 fractures were intra-articular. 55
      fractures were open. Substantial comminuted and segmental fractures occurred in
      57 cases and 35 cases, respectively. Multivariate analysis showed that increasing
      age was associated with delays in bony union and full weight bearing ability. An
      increase in the number of pack years smoked at the time of injury predicted the
      likelihood of knee stiffness, delays in bony union and full weight bearing
      ability. Higher injury severity scores were associated with delayed full weight
      bearing ability. The presence of open fractures predicted the likelihood of knee
      stiffness and delayed full weight bearing ability. Comminuted fractures were
      associated with malunion, and segmental fractures with delayed bony union. Using
      the outcome of floating knee injuries as fair or poor, according to Karlstrom and
      Olerud's criteria, we constructed a preoperative prognostic scoring scale which
      showed a sensitivity of 0.72 and a specificity of 0.90.

PMID- 11580129
TI  - Enhancement of human osteoblast proliferation and phenotypic expression when
      cultured in human serum.
AB  - Traditionally, culture medium is supplemented with foetal bovine serum (FBS).
      However, in cultures of osteoblasts intended for human re-implantation, such
      serum presents potential risks of foreign protein contamination and transmission
      of viral or prion-related material, if used. We cultured human osteoblasts from
      16 patients in 10% autologous human serum, 10% pooled human serum, 10% FBS or 2%
      Ultroser G. Non-synthetic sera were tested in both heat-treated and non-heat
      treated forms. We determined cell growth and osteoblast phenotype. Cell
      proliferation in all types of human serum was significantly greater than in FBS.
      This was most marked in heat-treated autologous human serum. Cells cultured in
      Ultroser G had less proliferation than all other groups. The phenotypic tests
      showed that cells cultured in human and foetal bovine serum displayed an
      osteoblast phenotype, with greater protein expression in cells cultured in human
      serum. We conclude that culture of human osteoblasts in autologous human serum
      enhances cell proliferation, while maintaining an osteoblast phenotype. These
      findings have implications for the use of cultured osteoblasts in self-cell
      therapy. Human osteoblast growth is supported by autologous human serum, which
      allows re-implantation of cultured cells, while avoiding the risk of foreign
      protein carry-over with enhancement of cell proliferation.

PMID- 11580130
TI  - Effects of a hydroxyl radical scavenger, EPC-K1, and neutrophil depletion on
      reperfusion injury in rat skeletal muscle.
AB  - Oxygen free radicals (OFR) and neutrophils are potent sources of reperfusion
      injury. We compared the effect of EPC-K1, a new OFR scavenger, and neutrophil
      depletion on the reperfusion injury in skeletal muscle, using an ischemic
      revascularized hindlimb model in rats. Warm ischemia, produced by vascular
      pedicle clamping, was sustained for 4 h. After 24 h of reperfusion, muscle
      function and damage were evaluated in 4 groups: a sham operation group, a control
      study group, a group treated by EPC-K1 (EPC group), and a group that received
      nitrogen mustard to induce neutropenia (NM group). Both the EPC and NM groups had
      limited muscle damage compared to the control group. The EPC group preserved
      muscle function significantly better than the control group and the mean
      isometric tetanic tension in the EPC group appeared to be higher than that in the
      NM group. Furthermore, levels of lipid peroxides in muscle and serum, and muscle
      edema in the EPC group, were significantly lower than in the NM group.
      Histological examinations supported these results. These findings suggest that
      limiting OFR generation by EPC-K1 in the early phase of reoxygenation is more
      potent than depletion of neutrophils in reducing reperfusion injury.

PMID- 11580131
TI  - Processing of morsellised femoral heads with high-pressure saline.

PMID- 11580132
TI  - One-stage surgical correction of congenital thoracic lordosis--report of 2 cases.

PMID- 11580133
TI  - Active tuberculosis of the hip treated with early total hip replacement--a report
      of 3 cases.

PMID- 11580134
TI  - Total knee arthroplasty in bilateral congenital dislocation of the patella--a
      case report.

PMID- 11580135
TI  - The Ilizarov method in total knee arthroplasty with nonunion of the proximal
      tibia--a case report.

PMID- 11580136
TI  - Scavenger cells with gram-positive bacterial lipoteichoic acid infiltrate around
      the damaged interlobular bile ducts of primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: Gram-positive bacterial DNA is frequently detectable in
      gallbladder bile of primary biliary cirrhosis (PBC) patients. To advance these
      findings, lipoteichoic acid (LTA) of gram-positive bacteria with high
      antigenicity was examined in liver specimens and bile from PBC patients and
      controls. METHODS: LTA was examined by Western blotting in the gallbladder bile
      from 15 PBC, 11 cholecystolithiasis and six normal subjects, and by
      immunohistochemistry in liver specimens from 16 PBC, six primary sclerosing
      cholangitis (PSC), eight chronic viral hepatitis C (CVH-C) and five normal
      subjects. RESULTS: In the gallbladder bile, there was no significant difference
      in the positive rate of LTA between PBC and controls. LTA-containing mononuclear
      cells were frequently detected in the portal tracts, particularly around the bile
      ducts and in hepatic sinusoids in PBC, while they were infrequent or occasional
      in control livers. These LTA-containing cells were sinusoidal endothelial cells
      and Kupffer cells, and portal monocytes, which frequently expressed scavenger
      receptor class B type 1. CONCLUSIONS: LTA derived from bacterial fragments may
      reach the bile, not only in the diseased state but also under normal conditions.
      Such LTA may be involved in the development and progression of portal tract
      lesions, particularly bile duct lesions, in PBC.

PMID- 11580137
TI  - Regulation of biliary cholesterol secretion is independent of hepatocyte
      canalicular membrane lipid composition: a study in the diosgenin-fed rat model.
AB  - BACKGROUND/AIMS: Phosphatidylcholine (PC) and sphingomyelin (SM) are the major
      phospholipids on the outer leaflet of the hepatocyte canalicular membrane. Since
      cholesterol preferentially associates with SM in detergent-resistant
      microdomains, we hypothesized that canalicular membrane lipid composition could
      modulate secretion of the sterol into bile. METHODS: Male Wistar rats were fed
      for 10 days with a control diet with or without the plant sterol diosgenin (1%
      w/w) to induce biliary cholesterol hypersecretion. Thereafter, lipid compositions
      and phospholipid molecular species were determined in fistula bile and highly
      enriched canalicular membrane fractions. RESULTS: Despite four-fold higher
      biliary cholesterol output in diosgenin-fed rats, no differences were observed
      between canalicular membranes of diosgenin and control groups with respect to
      cholesterol/phospholipid ratios (0.58 vs 0.62), phospholipid classes and acyl
      chain compositions of SMs (16:0 > 24:1 > 24:0 > 22:0 > 18:0 > 23:0 > 20:0 >
      24:2), or PCs (mainly diacyl 16:0-18:2, 16:0-20:4, 18:0-20:4, and 18:0-18:2). In
      contrast to canalicular PCs, bile contained more hydrophilic species (mainly
      diacyl 16:0-18:2 and 16:0-20:4), without differences between both groups. In
      vitro resistance of purified canalicular membrane fractions against detergents
      such as Triton X-100 and taurocholate was also similar in both groups.
      CONCLUSIONS: Diosgenin-induced biliary cholesterol hypersecretion occurs in the
      absence of changes of canalicular membrane lipids. Our data therefore do not
      support a major role of canalicular membrane lipid composition in regulation of
      biliary cholesterol secretion.

PMID- 11580139
TI  - Profiling the adult human liver transcriptome: analysis by cDNA array
      hybridization.
AB  - BACKGROUND/AIMS: A comprehensive profile of genes expressed at the mRNA level
      (transcriptome) in human liver tissue is important for elucidating the
      pathogenesis and treatment of hepatic diseases. The recent development of cDNA
      array hybridization allows the parallel monitoring of thousands of genes
      expressed in a single organ. METHODS: High-density microarrays containing 4043
      known and unique human cDNA gene targets were used to quantitatively analyze the
      expression of genes in human livers. Expressed gene transcripts were classified
      by function and listed with information of their chromosomal positions.
      Computational analysis was used to cluster genes according to similarity in
      pattern of gene expression. RESULTS: A total of 2418 unique gene transcripts were
      detected in five liver specimens. Through relational database analysis, we
      determined 1212 genes that were commonly expressed in 4 of the five liver
      specimens. Furthermore, analysis of the total 2418 expressed genes by self
      organizing maps and hierarchical clustering unexpectedly revealed a genomic acute
      phase response in two of the liver specimens. CONCLUSIONS: These findings
      represent a comprehensive preliminary molecular index of genes transcribed in the
      adult human liver. The information may serve as a resource for speeding up the
      discovery of genes underlying human hepatic diseases.

PMID- 11580138
TI  - Expression and DNA-binding activity of C/EBPalpha and C/EBPbeta in human liver
      and differentiated primary hepatocytes.
AB  - BACKGROUND/AIMS: Limited information is available on the expression and role of
      C/EBP factors in human liver and hepatocytes. We investigated the expression and
      DNA-binding activity of C/EBPalpha and C/EBPbeta in human liver needle biopsies,
      surgical lobectomies and differentiated cultured hepatocytes derived from
      lobectomies. METHODS: RNA and protein extracts were analyzed by RNAse protection,
      immunoblot and gel shift assays. RESULTS: C/EBP mRNAs, isoforms and DNA-binding
      activities were low/undetectable in lobectomies. In contrast, several C/EBPalpha
      (47, 45, 35 and 33 kDa) and C/EBPbeta isoforms (47, 43, 40, 35 and 21 kDa) were
      observed in needle biopsies. In cultured hepatocytes, the C/EBP expression
      pattern dramatically changed with time. C/EBPalpha mRNA and the 45 kDa isoform
      increased in parallel, reaching a maximum after 3-4 weeks coincident with weak
      DNA-binding activity. C/EBPbeta mRNA and isoform expression increased rapidly
      reaching a plateau within 1-2 weeks; all C/EBPbeta isoforms were phosphorylated.
      C/EBPbeta exhibited greater DNA-binding activity than C/EBPalpha, and this
      activity paralleled C/EBPbeta isoform expression. CONCLUSIONS: C/EBP isoforms
      exhibit markedly different expression patterns in lobectomies, needle biopsies
      and cultured hepatocytes. Stress stimuli during and/or after surgery for
      lobectomy resections may account for this difference. The pattern of C/EBP
      isoform expression in long-term highly differentiated cultured hepatocytes is
      close to that observed in needle biopsies.

PMID- 11580140
TI  - Rat liver slices as a tool to study LPS-induced inflammatory response in the
      liver.
AB  - BACKGROUND/AIMS: Inflammation in the liver is a complex interaction between
      parenchymal and non-parenchymal cells, and therefore can not be studied in vitro
      in pure cultures of these cells. METHODS: We investigated whether Kupffer cells
      in the liver slice are still responsive to an inflammatory stimulus of
      lipopolysaccharide (LPS), and evoke an inflammatory response in the hepatocytes.
      RESULTS: TNFalpha, IL-1beta and IL-10 were significantly elevated in culture
      medium of LPS-stimulated rat liver slices. Nitric oxide (NO) production of LPS
      treated slices gradually increased from 5 to 24 h (24 h: 81+/-5 microM vs. 14+/-2
      microM in control P < 0.05), paralleled by inducible nitric oxide synthase (iNOS)
      in the hepatocytes, iNOS mRNA was induced after 3 h. NO production but not iNOS
      induction was significantly inhibited by NOS inhibitors S-methylisothiourea and
      N(G)-nitro-L-arginine methylester. Both pentoxifylline and dexamethasone
      inhibited TNFalpha and IL-1beta production, albeit to a different extent, iNOS
      induction and, as a result thereof, NO production. CONCLUSIONS: These results
      imply that non-parenchymal cells in liver slices are viable and can be activated
      by LPS. In addition, it is concluded that the upregulation of iNOS in hepatocytes
      by LPS is caused by cytokines produced by Kupffer cells because inhibition of
      TNFalpha and IL-1beta production attenuated iNOS induction.

PMID- 11580141
TI  - Findings on liver biopsy to investigate abnormal liver function tests in the
      absence of diagnostic serology.
AB  - BACKGROUND/AIMS: The significance of abnormal liver function tests in the absence
      of diagnostic serology is unclear. The aim of this study was to report liver
      biopsy findings in a large group of patients with unexplained abnormal liver
      biochemistry. METHODS: Histological findings were examined in 354 patients who
      underwent liver biopsy to investigate abnormal liver function tests. RESULTS: Six
      percent of patients had a normal liver biopsy while 26% were found to have some
      degree of fibrosis and 6% were cirrhotic. Thirty four and 32% of biopsies
      suggested non-alcoholic steatohepatits or fatty liver respectively. Other
      diagnoses included cryptogenic hepatitis, drug toxicity, primary and secondary
      biliary cirrhosis, autoimmune hepatits, alcohol-related liver disease, primary
      sclerosing cholangitis, haemochromatosis, amyloid and glycogen storage disease.
      Patient management was directly altered in 18% of patients due to liver biopsy
      findings and three families were entered into screening programmes for
      inheritable liver disease. CONCLUSIONS: The finding of abnormal liver function
      tests in the absence of diagnostic serology may indicate significant liver
      disease. Liver biopsy yields a range of liver diseases of diverse nature and
      extent. Liver diseases may be uncovered for which specific treatment is
      indicated.

PMID- 11580142
TI  - Alpha B-crystallin expression in human and rat hepatic stellate cells.
AB  - BACKGROUND/AIMS: We searched for factors implicated in early hepatic stellate
      cell (HSC) activation in diseased liver, by means of suppression subtractive
      hybridization (SSH). METHODS: SSH was performed between messenger RNA (mRNA) from
      normal rat HSC and mRNA from HSC, isolated from rats with acute D-galactosamine
      (Gal)-induced hepatitis. RESULTS: One of the potentially upregulated factors
      which we found was alpha B-crystallin (ABCRYS), a small heat-shock protein and a
      chaperone known to protect the cell against protein degradation in conditions of
      cellular stress and known to associate with various types of intermediate
      filaments. Upregulation of ABCRYS mRNA in HSC, following Gal-intoxication (3.5
      fold) as well as by culturing the HSC on plastic (20-30-fold), was confirmed by
      quantitative real-time reverse transcription polymerase chain reaction. The
      expression of ABCRYS protein in human and rat HSC was demonstrated by
      immunohistochemistry, in vitro and in vivo, in normal and diseased liver. Double
      staining co-localized ABCRYS immunoreactivity with alpha-smooth muscle actin
      immunoreactivity in human liver and with desmin immunoreactivity in rat liver. In
      vivo upregulation of ABCRYS protein following Gal-intoxication was also shown, by
      comparison with desmin expression. CONCLUSIONS: Human and rat HSC express ABCRYS
      mRNA and protein. Both are rapidly upregulated following HSC activation.

PMID- 11580143
TI  - Survival and differentiation of porcine hepatocytes encapsulated by semiautomatic
      device and allotransplanted in large number without immunosuppression.
AB  - BACKGROUND/AIMS: The aim of this study was to evaluate the survival and functions
      of porcine hepatocytes transplanted in large quantities in the peritoneal cavity
      of allogeneic animals following semiautomatic encapsulation. METHODS: Isolated
      porcine hepatocytes and a polymer solution composed of AN69 were coextruded
      through a double lumen spinneret. Minitubes containing hepatocytes were
      transplanted in the peritoneal cavity of 12 pigs (4 x 10(9) cells/animal) in the
      absence of immunosuppressive therapy. Seven, 15, and 21 days after
      transplantation, minitubes was collected and processed for analyses. The
      morphology was examined under light and electron microscopy. Albumin synthesis
      was assessed by semi-quantitative reverse transcription-polymerase chain
      reaction. Cytochrome P450 3A (CYP3A) gene expression was analyzed by Western blot
      and by testosterone 6-beta-hydroxylation assay. RESULTS: The device allowed to
      encapsulate 55 x 10(6) hepatocytes/min. Hepatocytes exhibited normal structural
      and ultrastructural features up to day 21. Albumin gene expression decreased
      progressively between days 0 and 21. The amount of CYP3A protein and 6-beta
      hydroxylase activity were approximately 2-fold lower at days 7 and 15 than in
      freshly encapsulated hepatocytes, and further decreased thereafter. CONCLUSIONS:
      The preservation of hepatocyte functions during 1-2 weeks is encouraging for
      potential short-term use of such bioartificial liver in future clinical
      application.

PMID- 11580144
TI  - Macrophage inflammatory protein-2 induced by TNF-alpha plays a pivotal role in
      concanavalin A-induced liver injury in mice.
AB  - BACKGROUND/AIMS: Macrophage inflammatory protein-2 (MIP-2), one of the CXC
      chemokines, is involved in the recruitment of neutrophils in several tissue
      injuries. In this study, we investigated the role of MIP-2 in concanavalin A (Con
      A)-induced liver injury in mice. METHODS: Liver injury was induced by intravenous
      injection of Con A (15 mg/kg) and plasma alanine aminotransferase (ALT), MIP-2
      levels were determined and histological assessment of the liver was performed.
      Anti-mouse MIP-2 antibody was intravenously administered 30 min before Con A
      injection. RESULTS: The plasma ALT level significantly elevated and reached a
      maximum at 8 h after Con A injection. The plasma MIP-2 level was also elevated
      and reached a peak value at 2 h after Con A injection. The elevated ALT level by
      Con A injection was significantly inhibited by the MIP-2 antibody. The elevated
      plasma MIP-2 level after Con A injection was significantly reduced by the tumor
      necrosis factor alpha (TNF-alpha) antibody, and MIP-2 was induced in plasma after
      recombinant TNF-alpha injection. Hepatic necrosis and infiltration of neutrophils
      were observed after Con A injection, and these histological changes were
      attenuated by the MIP-2 antibody. CONCLUSIONS: These findings suggest that Con A
      induces TNF-alpha release, and this TNF-alpha stimulates MIP-2 induction, at
      least partially contributing to the liver injury mediated through the recruitment
      of neutrophils.

PMID- 11580145
TI  - Power Doppler signals after percutaneous ethanol injection therapy for
      hepatocellular carcinoma predict local recurrence of tumors: a prospective study
      using 199 consecutive patients.
AB  - BACKGROUND/AIMS: This study was prospectively conducted to elucidate the
      relationship between pre-/post-treatment power Doppler signals of hepatocellular
      carcinoma (HCC) and local recurrence. METHODS: One hundred ninety-nine
      consecutive patients with 359 HCC lesions receiving percutaneous ethanol
      injection therapy (PEIT) as a first-line option were enrolled. Arterial power
      Doppler signals in the tumor were found in 130 nodules, but not detected in 229.
      After confirmation of complete tumor necrosis on dynamic CT, Doppler signals in
      nodules were re-evaluated. Patients received periodical examinations to detect
      HCC recurrence. RESULTS: Local HCC recurrence was observed in 36 lesions;
      22%(28/130) of the pretreatment signal positive lesions, in contrast to 3.5%
      (8/229) of the pretreatment signal negative lesions (P < 0.01). Out of 130 signal
      positive nodules, signals disappeared in 120 (92%) after PEIT, but were present
      in ten (8%). During the 25-month follow up, local recurrence was detected in 19
      (16%) from the former, in contrast to nine (90%) from the latter (P < 0.001). Uni
      and multivariate Cox analysis revealed that the presence of pre-/post-treatment
      power Doppler signals, histological differentiation and tumor number were
      independent factors for local recurrence. However, 3-year recurrence rate of new
      lesions was 51%, but no predictors were identified. CONCLUSIONS: Residual Doppler
      signals in tumor after PEIT were related to the local HCC recurrence.

PMID- 11580146
TI  - Microsatellite instability and alternative genetic pathway in intrahepatic
      cholangiocarcinoma.
AB  - BACKGROUND/AIMS: Intrahepatic cholangiocarcinoma (ICC) arises from intrahepatic
      bile duct epithelium and is the second most prevalent among primary liver
      cancers. The aim of this study was to clarify the mechanism of
      cholangiocarcinogenesis. METHODS: We studied the incidence of microsatellite
      instability (MSI) involving eight highly polymorphic microsatellite markers and
      alternations of the K-ras, p53 and mdm-2 genes in human ICC tissues.
      Overexpression of mdm-2 oncoprotein was also immunohistochemically studied.
      RESULTS: Of all 65 cases examined, K-ras gene mutation was found in three cases
      (4.6%) at codon 12. Analysis of p53 alterations was performed in 28 cases
      including 22 frozen samples and mutations were found in three cases (10.7%).
      Overexpression of mdm-2 protein was observed in 25 (41.7%) out of 60 cases
      analyzed. In 22 frozen samples, seven (31.8%) cases showed mdm-2 amplification
      and four (18.2%) cases revealed MSI-positive phenotype. Among the cases analyzed,
      all the tumors with mdm-2 amplification/overexpression harbored the wild-type p53
      gene and all the microsatellite instability-positive cases were from mass-forming
      (MF) + periductal-infiltrating (PI) subtype. CONCLUSIONS: These results suggest
      that mdm-2 plays a role, which might be partially through inhibiting p53
      activity, in cholangiocarcinogenesis and that M

PMID- 11580147
TI  - Laminin deposition to type IV collagen enhances haptotaxis, chemokinesis, and
      adhesion of hepatoma cells through beta1-integrins.
AB  - BACKGROUND/AIMS: In hepatocellular carcinoma, laminin deposition to type IV
      collagen along the sinusoids is observed with the development of arterial
      network, coinciding with intrahepatic metastasis. We investigated the influence
      of laminin deposition to type IV collagen on hepatoma cell adhesion, motility and
      secretion of matrix metalloproteinases (MMPs), which are indispensable behaviors
      for tumor metastasis. METHODS: Hepatoma cell lines (KYN-1, -2 and -3) were used.
      The expression of integrin subunit mRNAs in hepatoma cells was confirmed by RT
      PCR. The influence of laminin addition to type IV collagen on the adhesion,
      chemokinesis, and migration of KYN-1, -2 and -3 was evaluated by the haptotactic
      migration, phagokinetic track motility, and cell adhesion assays. The effects of
      integrin subunits on these activities were evaluated using the function-blocking
      antibodies for integrins. Phosphorylation of MEK1/2 and secretion of MMPs were
      investigated by Western blotting and gelatin zymography. RESULTS: Integrin
      alpha1, alpha2, alpha3, alpha6 and beta1 subunit mRNAs were detected. The
      combination of type IV collagen and laminin enhanced the migration, chemokinesis,
      and adhesion of hepatoma cells compared to that of type IV collagen when used
      alone. The enhanced activity was significantly suppressed by function-blocking
      antibodies for integrin alpha1, alpha2, alpha3, alpha6 and beta1 subunits.
      Hepatoma cells cultured on the combination of type IV collagen and laminin showed
      phosphorylation of MEK1/2 and increased secretion of MMPs. CONCLUSIONS: The
      addition of laminin to type IV collagen enhances hepatoma cell adhesion and
      motility through beta1-integrins.

PMID- 11580148
TI  - Assessment of the benefits and risks of percutaneous biopsy before surgical
      resection of hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Because of a potential risk of needle tract seeding, the use of
      ultrasound (US)-guided biopsy for the diagnosis of hepatocellular carcinoma (HCC)
      is controversial. This study was aimed at determining the usefulness, accuracy
      and safety of this technique as well as the incidence of needle tract seeding.
      METHODS: From 1986 to 1996, 137 patients who underwent resection or
      transplantation for suspected HCC had US-guided biopsy before surgery. The
      analysis of the resected liver was compared to the results of biopsy. Patients
      were assessed with a mean follow up of 38 months. RESULTS: The diagnosis of HCC
      was established by biopsy in 122 patients (89%). Thirteen of the 15 patients with
      negative biopsy were shown to have HCC after surgery. The remaining two patients
      had non-malignant nodules. Sensitivity and accuracy of US-guided biopsy were 90
      and 91%, respectively. Accuracy was significantly influenced by the location of
      the nodule but not by its size. Needle tract seeding occurred in two patients
      (1.6%). CONCLUSIONS: In this series, the incidence of needle tract seeding was
      less than 2% and no recurrence was observed after local excision. This risk
      should be balanced with the risk of deciding an aggressive treatment in a patient
      without malignancy. Patients with negative biopsy should undergo a second biopsy
      and/or repeated investigations by imaging techniques.

PMID- 11580149
TI  - Increased levels of cytosolic thioredoxin reductase activity and mRNA in rat
      liver nodules.
AB  - BACKGROUND/AIMS: Thioredoxin reductase, a redox active enzyme, is induced in
      several tumors. This study focuses on the presence of and subcellular
      localisation of thioredoxin reductase in a tumor model where neoplastic lesions
      are selected by their resistance to the toxic effects of the promotor. METHODS:
      Liver nodules produced by intermittent feeding of 2-acetylaminofluorene to male
      Wistar rats were analyzed for thioredoxin reductase (TrxR) activity and mRNA.
      RESULTS: This activity was increased 3.5-fold in the cytosol but decreased 60% in
      the mitochondrial fraction compared to the liver of age-matched untreated
      animals. Only traces of activity were observed in the microsomal, plasma membrane
      and nuclear fractions from normal liver or nodules. The level of TrxR mRNA was 3
      fold higher in nodules than in normal rat liver. Furthermore, the total level of
      SH groups in homogenates was 2-fold higher in the case of the nodules.
      CONCLUSIONS: These findings indicate that the thioredoxin system makes an
      important contribution to the resistant phenotype of the neoplastic liver cell,
      which conveys a growth advantage of significance for tumor progression.

PMID- 11580150
TI  - Long-term follow-up of chronic hepatitis C in patients diagnosed at a tertiary
      care center.
AB  - BACKGROUND/AIMS: The natural history of chronic hepatitis C (HCV) is not
      completely understood. This study was aimed to evaluate the long-term outcome of
      the disease over a prolonged period of time and to identify factors associated
      with progression. METHODS: One hundred and sixteen patients with non-cirrhotic
      chronic non-A, non-B hepatitis consecutively diagnosed at a tertiary hospital
      between 1971 and 1977 were followed until December 1998 or until death. Patients
      with significant alcohol intake were excluded from the study. Variables obtained
      at the time of diagnosis, including epidemiological, clinical, laboratory, and
      histological data were recorded to determine risk factors associated with the
      development of liver cirrhosis and hepatic decompensation. RESULTS: Based on
      complete follow-up data, the development of liver cirrhosis and hepatic
      decompensation was evaluated in 94 and 114 of the 116 patients, respectively.
      Thirty-seven (39.3%) of 94 patients developed liver cirrhosis; an aspartate
      aminotransferase (AST) value higher than 70 IU/L was associated with development
      of cirrhosis (odds ratio (OR) 4.22, 95% CI 1.3-13.8). Hepatic decompensation
      occurred in 12 (10.5%) of 114 patients, its cumulative probability being 2.8% at
      10 years, 5.2% at 15 years and 19.8% at 20 years. The only factor independently
      associated to the development of hepatic decompensation was the presence of
      fibrosis (stage 2 or 3) in the initial liver biopsy (OR 4.1, IC 95% 1.22-13.9).
      Liver-related death occurred only in seven (6%) of 114 patients. In comparison
      with the 116 patients diagnosed in the 1970's, patients with chronic hepatitis C
      diagnosed in 1999 were younger, more often asymptomatic, had lower AST and
      alanine aminotransferase (ALT) values and had significantly lower grade and stage
      histological scores. CONCLUSIONS: In summary, chronic hepatitis C had a high rate
      of progression to liver cirrhosis over a prolonged follow-up. However, this might
      be related to the fact that two decades ago the diagnosis was made at a
      significantly more advanced stage of the disease. Patients at high risk of
      progression can be identified by biochemical and histological variables at the
      time of diagnosis.

PMID- 11580151
TI  - Maintenance therapy with gradual reduction of the interferon dose over one year
      improves histological response in patients with chronic hepatitis C with
      biochemical response: results of a randomized trial.
AB  - BACKGROUND/AIMS: Our aim was to assess whether histological response was improved
      by continuing interferon-alpha (IFN) treatment in patients with chronic hepatitis
      C (HCV) with a biochemical response and no viral clearance after a usual IFN
      treatment. METHODS: Fifty-seven patients with normal alanine aminotransferase
      (ALAT) levels and positive HCV RNA at the end of a 1 year IFN treatment were
      randomly assigned to either group 1 (n = 28) where IFN was stopped, or group 2 (n
      = 29) where IFN was continued for 1 more year with gradual reduction of the dose
      to keep serum ALAT activity below the upper limit of normal. Liver biopsies were
      obtained before, and then 6 months after the end of treatment. RESULTS: Knodell's
      index improved between paired biopsies in group 2 (8.2+/-2.4 vs. 5.5+/-2.1), but
      not in group 1 (8+/-2.3 vs. 6.5+/-2). In post-treatment biopsies, the METAVIR
      activity score was significantly lower in group 2 than in group 1 (0.7+/-0.2 vs.
      1.1+/-0.3, P < 0.05). In group 2, an improvement of the METAVIR fibrosis score
      was observed (1.3+/-0.4 vs. 1.1+/-0.2), whereas fibrosis progressed in group 1
      (1.3+/-0.4 vs. 1.6+/-0.4). CONCLUSIONS: Maintenance therapy by the minimal dose
      of IFN able to maintain biochemical response prevents histological progression in
      the sub-group of patients without virological response.

PMID- 11580152
TI  - Risk factors for diabetes mellitus and early insulin resistance in chronic
      hepatitis C.
AB  - BACKGROUND/AIMS: Our aims were to investigate the host and viral specific factors
      associated with diabetes mellitus (DM) and insulin resistance in chronic
      hepatitis C patients. METHODS: One hundred and three hepatitis C virus (HCV)
      infected were studied to assess the effects of HCV genotype, hepatic iron
      content, steatosis, hepatic fibrosis, body mass index (BMI) and family history of
      DM on the occurrence of DM. Insulin resistance (HOMA IR) was studied in 81 non
      diabetic patients to determine the mechanism associated with insulin resistance
      in this subgroup. RESULTS: Sixteen of the 123 were diabetic (13.0%). The
      variables predictive of DM were METAVIR fibrosis score 4 (OR, 13.16; P = 0.012),
      family history of diabetes (OR, 16.2; P = 0.0023), BMI (OR, 1.37; P = 0.017) and
      age (OR, 1.09; P = 0.002). In non-diabetic HCV-infected patients, HOMA-IR of
      METAVIR fibrosis score 0 and 1 patients were significantly different than score 2
      and score 3/4 patients. CONCLUSIONS: Our findings indicate that older age,
      obesity, severe liver fibrosis and family history of diabetes help identify those
      HCV patients who might have potential risk factors for development of DM. We
      observed that insulin resistance in non-diabetic HCV-infected patients was
      related to grading of liver fibrosis, and occurs already at an early stage in the
      course of HCV infection.

PMID- 11580153
TI  - Risk of parenterally transmitted hepatitis following exposure to surgery or other
      invasive procedures: results from the hepatitis surveillance system in Italy.
AB  - BACKGROUND/AIMS: To evaluate the strength of association between parenterally
      transmitted viral hepatitis and specific types of invasive procedures. METHODS:
      Data from the surveillance system for type-specific acute viral hepatitis
      (SEIEVA) during the period 1994-1999 were used. The association of acute
      hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with the potential
      risk factors (odds ratios (OR)) was estimated comparing 3120 hepatitis B and 1023
      hepatitis C cases with 7158 hepatitis A cases, used as controls, by multiple
      logistic regression analysis. RESULTS: Most procedures resulted in being
      associated with the risk of acquiring acute HBV or HCV. The strongest
      associations were: for HBV infection, abdominal surgery (adjusted OR = 3.9; 95%
      confidence intervals (CI) = 2.0-7.5), oral surgery (OR = 2.7; 95% CI = 1.6-4.5)
      and gynaecological surgery (OR = 2.6; 95% CI = 1.2-5.5); for HCV infection,
      obstetric/gynaecological interventions (OR = 12.1; 95% CI = 5.6-26.3), abdominal
      surgery (OR = 7.0; 95% CI = 3.2-14.9) and ophthalmological surgery (OR = 5.2; 95%
      CI = 1.1-23.2). Biopsy and/or endoscopy were associated with HCV, but not with
      HBV infection. CONCLUSIONS: Invasive procedures represent an important mode of
      HBV and HCV transmission. Since a large proportion of the adult general
      population is exposed to these procedures and an effective HCV vaccine is not yet
      available, non-immunological means of controlling iatrogenic modes of
      transmission are extremely important.

PMID- 11580154
TI  - Liver biopsy in elevated liver functions tests? An old question revisited.

PMID- 11580155
TI  - The pros and cons of gene expression analysis by microarrays.

PMID- 11580156
TI  - Oxidative stress-related molecules and liver fibrosis.

PMID- 11580157
TI  - Expression of liver steatosis in hepatitis C virus infection and pattern of
      response to alpha-interferon.

PMID- 11580158
TI  - Acute fatal hepatitis related to levofloxacin.

PMID- 11580159
TI  - Hepatotoxicity induced by fosinopril.

PMID- 11580160
TI  - A life-threatening complication of focal nodular hyperplasia.

PMID- 11580161
TI  - Impact of medical recommendations on alcohol consumption in HCV positive
      patients.

PMID- 11580162
TI  - The effects of mastery training and explicit feedback on task design preference
      in a vocational setting.
AB  - The purpose of this study was to examine the effects of mastery training and
      explicit feedback on the selection behavior of two individuals with severe mental
      retardation across two different vocational task designs. The two design options
      were (a) a site-based (traditional) approach, and (b) a more efficient motion
      economy based approach. The site-based design was developed from workshop
      standard task analyses. The motion-economy design was developed by re-configuring
      the site-based design using principles of motion economy and resulted in less
      distance movement required for task completion. The study was comprised of four
      assessment phases: (a) no experience (i.e., participant had no experience with
      either site-based or motion-economy based designs), (b) after training (i.e.,
      participant was trained to criterion level on both design options), (c) training
      and timer, and (d) training, timer, and work incentives. Selection behavior was
      affected by task efficiency, only when efficiency was made more salient by
      pairing task cues with work incentives.

PMID- 11580163
TI  - The use of 'Snoezelen' as multisensory stimulation with people with intellectual
      disabilities: a review of the research.
AB  - The past 15 years have seen a marked increase in the use of Snoezelen with a wide
      range of groups including people with intellectual disabilities. Research has
      been undertaken with respect to a variety of behaviors, notably changes in
      affect, challenging behavior, relaxation and interactions with both other persons
      and objects. Typically studies have adopted an applied behavior analysis
      approach, with a small number employing physiological measures. Research designs
      vary markedly in their technical adequacy and the participants have a wide range
      of intellectual disability, age, and additional characteristics such as autism.
      Much of the literature reviewed demonstrates a wide range of positive outcomes
      when Snoezelen Vs non-Snoezelen environments are contrasted, though there is
      little evidence of generalisation even to the immediate post-Snoezelen
      environment. Several studies, however, do yield entirely negative outcomes. It is
      difficult to attribute these differing outcomes to either participant
      characteristics or contrasted designs, given the diversity of approaches to
      evaluation and the relatively small number of studies. The review also addresses
      the issue of staff and carer attitudes and the place of Snoezelen in facilitating
      positive interactions, incidental to any specific sensory effects. Attention is
      drawn to the need to improve research designs in studying Snoezelen and to
      developing a clearer theoretical basis for use of this approach.

PMID- 11580164
TI  - Tower of Hanoi and working memory in adult persons with intellectual disability.
AB  - Persons with intellectual disability (ID) have been found to perform more poorly
      than their mental age would suggest in the visuo-spatial problem solving task
      Tower of Hanoi (TOH). Inefficient performance has been assumed to be related to
      inability to use sophisticated problem solving strategies because of restricted
      working memory capacity. In the present study, the TOH performance of adult
      persons with ID was found to be equal to that of fluid-intelligence-matched
      general children. However, persons with ID violated the rules of the TOH more
      often, and needed more trials to solve the TOH problems than the children did.
      Visuo-spatial and executive working memory tasks were significantly connected to
      the TOH performance of persons with ID, whereas phonological working memory tasks
      were not. Poor inhibition ability was related to the poor performance of subjects
      with ID in the TOH. We suggest that for persons with ID, TOH performance is
      determined by individual differences in fluid intelligence, controlled attention,
      and inhibition ability.

PMID- 11580165
TI  - Assessment instruments used in the education and treatment of persons with
      autism: brief report of a survey of national service centers.
AB  - Although assessment is a critical component in the education and treatment of
      persons who have autism, there is insufficient information about the types of
      assessment instruments that are used routinely by practitioners. This brief
      report describes a survey of national service centers to determine their use of
      standardized instruments and the purposes of their assessment practices. Data
      from centers representing 30 states revealed that (a) the number of assessment
      instruments endorsed by centers increased as centers adopted a
      "multidisciplinary" approach to education and treatment, (b) the largest
      proportion of instruments fell within intellectual, motor, and
      language/communication domains, and (c) instruments were used most frequently for
      diagnostic and curriculum design purposes. Agreement among practitioners on the
      selection of instruments occurred most frequently in the domains of projective,
      adaptive behavior, and family assessment. The implications from these findings
      for assessment practices in autism are discussed.

PMID- 11580166
TI  - Antecedent control of sleep-awakening disruption.
AB  - The sleep-awakening disruption of an adolescent with developmental disabilities
      was treated using an antecedent control intervention that identified his
      consistent time of wake-up, provided the presence of a preferred staff in his
      bedroom, and prompted social interaction from staff before challenging behaviors
      occurred. Positive findings were documented using a combined reversal and
      multiple baseline across settings design, with results maintained through a 9
      month follow-up. A partial component analysis of the intervention plan suggested
      that the presence of preferred staff was the influential antecedent variable.

PMID- 11580167
TI  - Teaching children with autism to answer novel wh-questions by utilizing a
      multiple exemplar strategy.
AB  - This study investigated the transfer and maintenance of question-answering skills
      in five children diagnosed with autism. A multiple baseline design across classes
      of questions (i.e., what, where, who and why) was applied for each child.
      Question-answer exemplars were selected within each class, and each class was
      trained separately in consecutive order. The dependent variable was the
      proportion of appropriate answers (i.e., complete sentences) to novel questions
      within each class, on first trial. The results showed that all children became
      able to answer novel questions with complete sentences within each of the classes
      that were trained, and they showed transfer of these skills across persons,
      settings and time. The findings support the use of analogous question-answer
      exemplars in order to facilitate response-transfer to novel questions. It is also
      suggested that this type of transfer is more likely to occur if the answers
      trained are in full sentence and there is a structural correspondence between the
      question and the answer in each single exemplar and across exemplars within a
      class of questions.

PMID- 11580168
TI  - Monte Carlo dose verification for intensity-modulated arc therapy.
AB  - Intensity-modulated arc therapy (IMAT), a technique which combines beam rotation
      and dynamic multileaf collimation, has been implemented in our clinic. Dosimetric
      errors can be created by the inability of the planning system to accurately
      account for the effects of tissue inhomogeneities and physical characteristics of
      the multileaf collimator (MLC). The objective of this study is to explore the use
      of Monte Carlo (MC) simulation for IMAT dose verification. The BEAM/DOSXYZ Monte
      Carlo system was implemented to perform dose verification for the IMAT treatment.
      The implementation includes the simulation of the linac head/MLC (Elekta SL20),
      the conversion of patient CT images and beam arrangement for 3D dose calculation,
      the calculation of gantry rotation and leaf motion by a series of static beams
      and the development of software to automate the entire MC process. The MC
      calculations were verified by measurements for conventional beam settings. The
      agreement was within 2%. The IMAT dose distributions generated by a commercial
      forward planning system (RenderPlan. Elekta) were compared with those calculated
      by the MC package. For the cases studied, discrepancies of over 10% were found
      between the MC and the RenderPlan dose calculations. These discrepancies were due
      in part to the inaccurate dose calculation of the RenderPlan system. The
      computation time for the IMAT MC calculation was in the range of 20-80 min on 15
      Pentium-Ill computers. The MC method was also useful in verifying the beam
      apertures used in the IMAT treatments.

PMID- 11580169
TI  - A method of simulating dynamic multileaf collimators using Monte Carlo techniques
      for intensity-modulated radiation therapy.
AB  - A method of modelling the dynamic motion of multileaf collimators (MLCs) for
      intensity-modulated radiation therapy (IMRT) was developed and implemented into
      the Monte Carlo simulation. The simulation of the dynamic MLCs (DMLCs) was based
      on randomizing leaf positions during a simulation so that the number of particle
      histories being simulated for each possible leaf position was proportional to the
      monitor units delivered to that position. This approach was incorporated into an
      EGS4 Monte Carlo program, and was evaluated in simulating the DMLCs for Varian
      accelerators (Varian Medical Systems, Palo Alto. CA, USA). The MU index of each
      segment, which was specified in the DMLC-control data, was used to compute the
      cumulative probability distribution function (CPDF) for the leaf positions. This
      CPDF was then used to sample the leaf positions during a real-time simulation,
      which allowed for either the step-shoot or sweeping-leaf motion in the beam
      delivery. Dose intensity maps for IMRT fields were computed using the above Monte
      Carlo method, with its accuracy verified by film measurements. The DMLC
      simulation improved the operational efficiency by eliminating the need to
      simulate multiple segments individually. More importantly, the dynamic motion of
      the leaves could be simulated more faithfully by using the above leaf-position
      sampling technique in the Monte Carlo simulation.

PMID- 11580170
TI  - Monte Carlo aided room scatter studies in the primary air kerma strength
      standardization of a remote afterloading 192Ir HDR source.
AB  - Corrections for room scatter, [ksc(d, H)]RM, were derived using Monte Carlo
      methods for rooms of various sizes, including the brachytherapy treatment room,
      in which primary air kerma strength standardization of a remote afterloading
      microSelectron 192Ir HDR source was carried out, using a 60 cm3 spherical
      graphite ion chamber. It was observed that for a given source-to-floor height, H,
      the air kerma rate due to room scatter was found to be decreasing with increase
      in source-to-detector distance, d, whereas it is assumed to be constant in the
      experimental determination (multiple-distance method) of the air kerma strength
      (AKS). Irrespective of the room size considered in the present study and when H =
      100 cm, the assumption of 'constant room scatter' for d = 50, 75 and 100 cm
      resulted in overestimation of the AKS by about 1%. However, when d was in the
      range 13-25 cm, it was only 0.20%. The room scatter correction for the shadow
      cone method was also computed and the result showed that no additional correction
      was required on account of forward scatter from the cone. Further, at larger d
      (50-100 cm), the number of low-energy photons (40-200keV) relative to the total
      number of photons was found to be very significant, which may be useful to
      revisit the Spencer-Attix cavity theory.

PMID- 11580171
TI  - Using serial imaging data to model variabilities in organ position and shape
      during radiotherapy.
AB  - A model is proposed for incorporating the effects of organ motion into the
      calculation of dose in a statistical fashion based on serial imaging measurements
      of organ motion. These measurements can either come from a previously studied
      population of patients, or they can be specific to the particular patient
      undergoing therapy. The statistical distribution underlying the measurements of
      organ motion, including the changes in organ shape, is reconstructed non
      parametrically without requiring any assumptions about its functional form. The
      model is thus capable of simulating organ motions that are not present in the
      original measurements, yet nonetheless come from the same underlying statistical
      distribution. The present model overcomes two particular limitations of many
      organ motion models: (a) the fact that they do not account for changes in organ
      shape, and (b) the fact that they make physically unrealistic assumptions about
      the functional form of the statistical distribution of organ motion, such as
      assuming that it is Gaussian. The present model can form the foundation of
      methods for the more accurate and clinically relevant calculation of the dose to
      the target volume and normal tissues.

PMID- 11580172
TI  - Numerical analysis of a model of organ motion using serial imaging measurements
      from prostate radiotherapy.
AB  - We previously proposed a model for incorporating the effects of organ motion,
      including the changes in organ shape, into the calculation of dose in a
      statistical fashion based on serial imaging measurements of organ motion. In the
      present paper, numerical studies were used to investigate how the accuracy of the
      statistical calculation of dose depends on the number of organ motion
      measurements provided as input into the model. The dose calculated statistically
      with the model was consistently more accurate than the one obtained by directly
      resampling the serial measurements of organ motion. It was also more robust
      relative to the random variabilities present in the input organ motion
      measurements. The results confirm that the model can reproduce the statistical
      distribution of the organ motions measured in a serial imaging study, including
      the changes in organ shape, without making any assumptions about the functional
      form of this distribution. The model allows a more accurate calculation of dose
      to be performed from a given number of measurements of organ motion than would
      otherwise be obtained by directly resampling the measured data. It thus maximizes
      the information that is extracted from serial imaging measurements.

PMID- 11580173
TI  - Light dosimetry using the P3 approximation.
AB  - In earlier work, we demonstrated that radiance, calculated using the P3
      approximation in a plane wave geometry, could be used to accurately predict the
      optical parameters of an Intralipid/methylene blue phantom. Plane wave geometry
      is impractical for clinical use but the results of this work encouraged us to
      further develop the P3 approximation for a spherical geometry, described in this
      paper. Radiance predicted by this model for a defined Intralipid/methylene blue
      phantom was compared with radiance measured in this phantom. The results
      demonstrate that the spherical derivation of the P3 approximation will
      reproducibly predict optical parameters of a tissue phantom as effectively as the
      slab geometry derivation of the P3 approximation. In a similar protocol, the P3
      approximation was used to estimate the optical parameters of ex vivo human
      prostate. Radiance in this case was measured in the prostate samples using an
      after loading technique. Three prostate samples tested were found to be
      surprisingly optically homogeneous. The after loading protocol described in this
      paper could form the basis of a minimally invasive and effective clinical method
      to optically characterize human prostate.

PMID- 11580174
TI  - 7Li relaxation time measurements at very low magnetic field by 1H dynamic nuclear
      polarization.
AB  - Dynamic nuclear polarization (DNP) of water protons was used to measure the
      relaxation time of lithium at very low magnetic field as a demonstration of the
      use of DNP for nuclei less abundant than water protons. Lithium (Li+) was chosen
      because it is an efficient treatment for manic-depressive illness, with an
      unknown action mechanism. After having recalled the theoretical basis of a three
      spin system comprising two nuclei-the water proton of the solvent, the dissolved
      Li+ ion and the free electron of a free radical-we have developed a transient
      solution in order to optimize potential biological applications of Li DNP. The
      three-spin model has allowed computation of all the parameters of the system-the
      longitudinal relaxation rate per unit of free radical concentration, the dipolar
      and scalar part of the coupling between the nuclei and the electron. and the
      maximum signal enhancement achievable for both proton and lithium spins. All
      these measurements have been obtained solely through the detection of the proton
      resonance.

PMID- 11580175
TI  - Melanin and blood concentration in human skin studied by multiple regression
      analysis: experiments.
AB  - Knowledge of the mechanism of human skin colour and measurement of melanin and
      blood concentration in human skin are needed in the medical and cosmetic fields.
      The absorbance spectrum from reflectance at the visible wavelength of human skin
      increases under several conditions such as a sunburn or scalding. The change of
      the absorbance spectrum from reflectance including the scattering effect does not
      correspond to the molar absorption spectrum of melanin and blood. The modified
      Beer-Lambert law is applied to the change in the absorbance spectrum from
      reflectance of human skin as the change in melanin and blood is assumed to be
      small. The concentration of melanin and blood was estimated from the absorbance
      spectrum reflectance of human skin using multiple regression analysis. Estimated
      concentrations were compared with the measured one in a phantom experiment and
      this method was applied to in vivo skin.

PMID- 11580176
TI  - Melanin and blood concentration in a human skin model studied by multiple
      regression analysis: assessment by Monte Carlo simulation.
AB  - Measurement of melanin and blood concentration in human skin is needed in the
      medical and the cosmetic fields because human skin colour is mainly determined by
      the colours of melanin and blood. It is difficult to measure these concentrations
      in human skin because skin has a multi-layered structure and scatters light
      strongly throughout the visible spectrum. The Monte Carlo simulation currently
      used for the analysis of skin colour requires long calculation times and
      knowledge of the specific optical properties of each skin layer. A regression
      analysis based on the modified Beer-Lambert law is presented as a method of
      measuring melanin and blood concentration in human skin in a shorter period of
      time and with fewer calculations. The accuracy of this method is assessed using
      Monte Carlo simulations.

PMID- 11580177
TI  - Changes in relative light fluence measured during laser heating: implications for
      optical monitoring and modelling of interstitial laser photocoagulation.
AB  - Dynamic changes in internal light fluence were measured during interstitial laser
      heating of tissue phantoms and ex vivo bovine liver. In albumen phantoms, the
      results demonstrate an unexpected rise in optical power transmitted approximately
      I cm away from the source during laser exposure at low power (0.5-1 W), and a
      decrease at higher powers (1.5-2.5 W) due to coagulation and possibly charring.
      Similar trends were observed in liver tissue, with a rise in interstitial fluence
      observed during 0.5 W exposure and a drop in interstitial fluence seen at higher
      powers (1-1.5 W) due to tissue coagulation. At 1.5 W irradiation an additional,
      later decrease was also seen which was most likely due to tissue charring.
      Independent spectrophotometric studies in Naphthol Green dye indicate the rise in
      fluence observed in the heated albumen phantoms may have been primarily due to
      light exposure causing photobleaching of the absorbing chromophore. and not due
      to heat effects. Experiments in liver tissue demonstrated that the observed rise
      in fluence is dependent on the starting temperature of the tissue. Correlating
      changes in light fluence with key clinical endpoints/events such as the onset of
      tissue coagulation or charring may be useful for on-line monitoring and control
      of laser thermal therapy via interstitial fluence sensors.

PMID- 11580178
TI  - Electrical coupling between smooth muscle and endothelium in arterioles of the
      guinea-pig small intestine.
AB  - Equations describing the steady-state passive electrical properties of arterioles
      have been derived. The arteriole was modelled as having two thin layers of cells
      (muscle and endothelium) with strong electrical coupling between cells within a
      layer and variable coupling between the layers. The model indicated that spread
      of membrane potential changes was highly dependent on the thickness of cells
      within the layers. The model was also used to identify the optimal experimental
      strategy for detecting coupling between the two layers, and experiments were
      carried out on arterioles from the guinea-pig small intestine. Thickness of the
      endothelial layer was measured using electron microscopy and was found to be
      around 0.5 microm. Electrical input resistance was measured in intact arterioles
      and compared to input resistance of arterioles from which the endothelium had
      been removed. The experiments confirmed that there was a strong electrical
      coupling between the muscle and endothelium in these vessels.

PMID- 11580179
TI  - A monte carlo approach to electron contamination sources in the Saturne-25 and 
      41.
AB  - The various components of the accelerator treatment head act as sources of
      contaminating electrons. The presence of contamination electrons increases the
      surface dose, which deteriorates the skin-sparing effect. The present study
      examines the sources of this 'contamination', the influence on the surface dose
      and the shape of the build-up curve. The Monte Carlo simulation of two linear
      accelerators, Saturne-25 and -41, allowed us to study the influence of electron
      contamination in various therapeutic energies and in different geometries. The
      Saturne-25 and -41 cover a wide range of therapeutic energies with nominal
      energies 12/23 MV and 6/15 MV, respectively. The analysis of the results shows
      that at a source-to-surface distance of 100 cm and a wide opening of the
      collimators, the main sources of contaminating electrons are the flattening
      filter and the air below it. The contribution of the secondary contamination
      electrons on the surface dose is 16% for 6 MV and 12 MV, 6% for 15 MV and 17% for
      23 MV. The energy spectra of electrons coming from the flattening filter and the
      air below it are completely different. The air produces electrons of low
      energies. The mean energies of these spectra vary from 1 MeV to 2 MeV depending
      on the nominal energy of the photon beam. The secondary electrons generated by
      the flattening filter produce a wide energy spectrum with mean energies of the
      same order of the bremsstrahlung spectrum. The flattening filter absorbs the
      secondary electrons generated in the target, the primary collimator and the air
      inside the head.

PMID- 11580180
TI  - Verification of the super-omni wedge concept.
AB  - This study verifies the concept of the super-omni wedge by validating its
      equations for effective wedge orientation and wedge angle and by comparing the
      dose distributions it produces with those produced by other wedge techniques. To
      validate the equations, we calculated dose distributions for 20 combinations of
      wedge orientations and wedge angles: we then determined the differences between
      the wedge orientations and angles predicted by the equations and those calculated
      by a three-dimensional treatment-planning system. To compare the super-omni wedge
      concept with other techniques, we calculated the dose and position differences
      between the dose distributions produced by the super-omni wedge concept and those
      produced by other wedge techniques. The error of wedge orientations ranged from 
      0.5 degrees to 0.4 degrees, and that of wedge angles ranged from -0.6 degrees to
      1.7 degrees. The dose distributions produced by the super-omni wedge were similar
      and therefore equivalent to those produced by other wedge techniques. Serving as
      an intermediate step in treatment-planning optimization. the super-omni wedge is
      a reliable method for producing wedged dose distributions with arbitrary wedge
      orientations and wedge angles.

PMID- 11580181
TI  - Optimization of the step-and-shoot leaf sequence for delivery of intensity
      modulated radiation therapy using a variable division scheme.
AB  - To deliver an intensity modulated radiation therapy (IMRT) plan by multileaf
      collimator (MLC) it is necessary to convert beam profiles, generated from the
      inverse treatment planning algorithm, into a series of instructions that the MLC
      control system can execute. An idealized IMRT beam profile can be regarded as a
      continuously varying two-dimensional function and is usually represented by an
      intensity map, i.e., a discretized description in space and in intensity of the
      beam profile. It is common to assume that the intensity map be defined over a
      regular grid with N steps and equal increments of intensity levels. In reality,
      this may not be the optimal representation of the beam profile and may introduce
      unnecessary discrepancies between the intensity pattern delivered and that
      ideally required. We have implemented an algorithm capable of minimizing the
      difference between the two patterns on a beam specific basis. In other words, it
      can produce optimized intensity maps, individually produced to suit the
      (continuous function) intensity profile they are intended to approximate. This
      enhancement in conformation is achieved by allowing variable step size and
      unconstrained intensity levels in the final leaf sequence.

PMID- 11580182
TI  - Computer-assisted selection of coplanar beam orientations in intensity-modulated
      radiation therapy.
AB  - In intensity-modulated radiation therapy (IMRT), the incident beam orientations
      are often determined by a trial and error search. The conventional beam's-eye
      view (BEV) tool becomes less helpful in IMRT because it is frequently required
      that beams go through organs at risk (OARs) in order to achieve a compromise
      between the dosimetric objectives of the planning target volume (PTV) and the
      OARs. In this paper, we report a beam's-eye view dosimetrics (BEVD) technique to
      assist in the selection of beam orientations in IMRT. In our method, each beam
      portal is divided into a grid of beamlets. A score function is introduced to
      measure the 'goodness' of each beamlet at a given gantry angle. The score is
      determined by the maximum PTV dose deliverable by the beamlet without exceeding
      the tolerance doses of the OARs and normal tissue located in the path of the
      beamlet. The overall score of the gantry angle is given by a sum of the scores of
      all beamlets. For a given patient. the score function is evaluated for each
      possible beam orientation. The directions with the highest scores are then
      selected as the candidates for beam placement. This procedure is similar to the
      BEV approach used in conventional radiation therapy, except that the evaluation
      by a human is replaced by a score function to take into account the intensity
      modulation. This technique allows one to select beam orientations without the
      excessive computing overhead of computer optimization of beam orientation. It
      also provides useful insight into the problem of selection of beam orientation
      and is especially valuable for complicated cases where the PTV is surrounded by
      several sensitive structures and where it is difficult to select a set of 'good'
      beam orientations. Several two-dimensional (2D) model cases were used to test the
      proposed technique. The plans obtained using the BEVD-selected beam orientations
      were compared with the plans obtained using equiangular spaced beams. For all the
      model cases investigated, the use of BEVD-selected beam orientations improved the
      dose distributions significantly. These examples indicate that the technique has
      considerable potential for simplifying the IMRT treatment planning process and
      allows for better utilization of the technical capacity of IMRT.

PMID- 11580183
TI  - Calibration of ionization chambers in air kerma length.
AB  - Pencil ionization chambers are employed for the direct determination of the
      computed tomography dose index (CTDI), which is used for patient dosimetry in CT
      examinations. The chambers are calibrated in air kerma length in a reference x
      ray field. The precision of calibration is influenced by several factors which
      are investigated in the present work. It is shown that the best irradiation
      length is 50% of the chamber rated length. The reading must be corrected for a
      residual signal due to the irradiation of the sensitive chamber volume by
      scattered radiation. The origin of this radiation is identified mainly at the
      edges of the diaphragm limiting the useful field. The residual signal is
      determined by a linear fit of measurements performed at minimum of three
      diaphragm apertures. The optimum geometric conditions are also discussed.

PMID- 11580184
TI  - Application of diamond detectors to the dosimetry of 45 and 100 kvp therapy
      beams: comparison with a parallel-plate ionization chamber and Monte Carlo.
AB  - Diamond detectors have become an increasingly popular dosimetric method where
      either high spatial resolution is required or where photon or electron spectra
      are likely to change with depth or field size. However, little work has been
      previously reported for superficial energies. This paper reports the response of
      a commercially available diamond detector (PTW Freiburg/IPTB Dubna) at 45 kVp
      (0.55 mm Al first HVL) and 100 kVp (2.3 mm Al first HVL) including dose and dose
      rate linearity, percentage depth-dose and output factors as a function of
      applicator size. Comparisons are made with Br J. Radiol. supplement 25 data,
      measurements using a PTW parallel-plate chamber and Monte Carlo simulations based
      on spectra determined from transmission measurements in aluminium. Excellent
      agreement was obtained for percentage depth-dose curves between Monte Carlo and
      diamond after correcting for sublinearity of the dose-rate response and energy
      dependence of the diamond detector. However, significant differences were noted
      between diamond/Monte Carlo and the parallel-plate chamber, which is attributed
      to the perturbation caused by the polyethylene base of the chamber

PMID- 11580185
TI  - A fast algorithm to find optimal controls of multiantenna applicators in regional
      hyperthermia.
AB  - The goal of regional hyperthermia is to heat up deeply located tumours to
      temperatures above 42 C while keeping the temperatures in normal tissues below
      tissue-dependent critical values. The aim of this paper is to describe and
      analyse functions which can be used for computing hyperthermia treatment plans in
      line with these criteria. All the functionals considered here can be optimized by
      efficient numerical methods. We started with the working hypothesis that
      maximizing the quotient of integral absorbed power inside the tumour and a
      weighted energy norm outside the tumour leads to clinically useful power
      distributions which also yield favourable temperature distributions. The
      presented methods have been implemented and tested with real patient data from
      the Charite Berlin. Campus Virchow-Klinikum. The results obtained by these fast
      routines are comparable with those obtained by relatively expensive global
      optimization techniques. Thus the described methods are very promising for online
      optimization in a hybrid system for regional hyperthermia where a fast response
      to MR-based information is important.

PMID- 11580186
TI  - Fluorescence nanotomography using resonance energy transfer: demonstration with a
      protein-sugar complex.
AB  - A new approach to structural sensing, fluorescence resonance energy transfer
      nanotomography, which interprets fluorescence decay measurement in terms of site
      density analysis of molecular distributions, has been applied to a glucose sensor
      based on competitive binding with malachite green labelled dextran to the sugar
      binding protein concanavalin A labelled with allophycocyanin. Opportunities for
      structural sensing in clinical medicine are highlighted.

PMID- 11580187
TI  - How accurate is a CT-based dose calculation on a pencil beam TPS for a patient
      with a metallic prosthesis?
AB  - The accuracy of a CT-based dose calculation on a treatment planning system (TPS)
      for a radiotherapy patient with a metallic prosthesis has not previously been
      reported. In this study, the accuracy of the CT-based inhomogeneity correction on
      a pencil beam TPS (Helax TMS) was determined in a phantom containing a metallic
      prosthesis. A steel prosthesis phantom and a titanium prosthesis phantom were
      investigated. The phantoms were CT-scanned and dose plans produced on the TPS,
      using the CT images to provide density information for the inhomogeneity
      corrections. Verification measurements were performed on a linear accelerator for
      6 and 15 MV x-rays. Measured dose profiles at three different depths were
      compared to the calculations of the TPS. For the titanium prosthesis and for 6 MV
      x-rays, the TPS overestimated the beam attenuation by approximately 20% at 15 and
      20 cm depths in the phantom. This is due to a limitation in the density
      allocation of this TPS: any Hounsfield number (HN) above a certain threshold is
      allocated the density of steel. For the steel prosthesis, the TPS performed the
      correct mapping of HN to mass density. The dose calculation was within 6% for 6
      MV x-rays at 15 and 20 cm depths. However. the accuracy of dose calculation
      varied with beam energy and depth, with large errors in the region close to the
      prosthesis. The TPS overestimated the dose by 11% for 6 MV and 15% for 15 MV x
      rays at 11 cm depth. 2.5 cm beyond the steel prosthesis. These results highlight
      the limitations in the density allocation of this TPS and demonstrate
      shortcomings in the pencil beam dose calculation.

PMID- 11580188
TI  - The interaction between Terahertz radiation and biological tissue.
AB  - Terahertz (THz) radiation occupies that region of the electromagnetic (EM)
      spectrum between approximately 0.3 and 20 THz. Recent advances in methods of
      producing THz radiation have stimulated interest in studying the interaction
      between radiation and biological molecules and tissue. Given that the photon
      energies associated with this region of the spectrum are 2.0 x 10(-22) to 1.3 x
      10(-20) J, an analysis of the interactions requires an understanding of the
      permittivity and conductivity of the medium (which describe the bulk motions of
      the molecules) and the possible transitions between the molecular energy levels.
      This paper reviews current understanding of the interactions between THz
      radiation and biological molecules, cells and tissues. At frequencies below
      approximately 6 THz. the interaction may be understood as a classical EM wave
      interaction (using the parameters of permittivity and conductivity), whereas at
      higher frequencies. transitions between different molecular vibrational and
      rotational energy levels become increasingly important and are more readily
      understood using a quantum-mechanical framework. The latter is of particular
      interest in using THz to probe transitions between different vibrational modes of
      deoxyribonucleic acid. Much additional experimental work is required in order to
      fully understand the interactions between THz radiation and biological molecules
      and tissue.

PMID- 11580189
TI  - Synthesis and stereochemical characterization of diastereomeric nucleoside
      phosphorothioselenoates by NMR methods.
AB  - Synthesis and stereochemical characterization of enantiomerically pure nucleoside
      phosphorothioselenoates are reported. The effects of solvent and temperature on
      the vicinal carbon-phosphorus couplings are described and the results are
      interpreted in terms of conformational changes influenced by stacking
      interactions between the bases and the phenyl rings.

PMID- 11580190
TI  - Thiosugars. VIII. Preparation of new 4'-thio-L-lyxo pyrimidine nucleoside
      analogues.
AB  - Reaction of 1-O-acetyl-2,3,5-tri-O-benzyl-4-thio-L-lyxofuranose with silylated
      pyrimidine bases and subsequent deprotection with boron tribromide led to 4'-thio
      L-lyxo pyrimidine nucleosides. The 5-bromo-6-methyl derivative was prepared from
      methyl 2,3,5-tri-O-acetyl-4-thio-L-lyxofuranoside. Deacetylation was performed
      with sodium methoxide. The anomers were separated by HPLC and their
      configurations assigned by NMR spectroscopy and X-ray structural analyses. The
      biological activity of the nucleosides was tested.

PMID- 11580191
TI  - A novel affinity chromatography method for the co-purification of deoxycytidine
      kinase and cytidine deaminase.
AB  - By affinity chromatography with Sepharose coupled to 2'-deoxy-1-beta-D
      ribofuranosyl-N4-dodecanoylcytosine, deoxycytidine kinase and cytidine deaminase
      were purified 1,950- and 2,240-fold, respectively, from Ehrlich carcinoma cells,
      and their enzyme activities for several deoxycytidine analogs were investigated.

PMID- 11580192
TI  - Synthesis of 5-alkenylated D4T analogues via the Pd-catalyzed cross-coupling
      reaction.
AB  - The target compounds 5-[N-(6-amino-hexyl)-acrylamide]-2',3'-didehydro-2',3'
      dideoxy-uridine (12) and 5-[N-[5-(methoxycarbonyl)-pentyl]-acrylamide]-2',3'
      didehydro-2',3'- dideoxy-uridine (15) were prepared by the palladium acetate
      triphenylphosphine-catalyzed reaction of the 5'-O-acetyl-5-iodo-d4T analogue (3).
      These compounds 12 and 15 can be used to prepare nucleotide probes carrying
      fluorescent labels and were nevertheless screened for their anti-HIV activity.
      The biological data demonstrated that none of them were active against HIV-1.

PMID- 11580193
TI  - Synthesis and structure determination of some oxadiazole-2-thione and triazole-3
      thione galactosides.
AB  - The syntheses of 5-pyridyl-3(beta-D-galactopyranosyl)-1,3,4-oxadiazole-2-thiones
      3a-3c and 5-pyridyl-2(beta-D-galactopyranosyl)-4-benzyl-1,2, 4-triazole-3-thiones
      6a-6c are reported. The existence of N-galactosides--not S-galactosides--was
      proven by IR and 15N NMR spectroscopy. The structures of the final products and
      the intermediates were elucidated by IR, 1H, 13C and 15N NMR spectroscopy and
      mass spectrometry.

PMID- 11580194
TI  - Novel reversion reaction of D-arabino-hexose phenylosotriazole. A useful model in
      natural glycoside and polysaccharide analysis.
AB  - Treatment of D-arabino-hexose phenylosotriazole with conc. hydrochloric acid
      afforded a new type of alpha- and beta-glycosides of D-erythrose formed by
      reaction of the 3,6-anhydro derivative with the in situ formed 2-phenyl-4
      (formylmethyl)- 1,2,3-triazole.

PMID- 11580195
TI  - Synthesis of certain 2'-deoxyuridine derivatives containing substituted phenoxy
      groups attached to C-5'; evaluation as potential dUTP analogues.
AB  - Derivatives of 2'-deoxyuridine in which the 5'-OH group is replaced by a 2,3,6
      trifluoro-5-hydroxy-4-nitrophenoxy or a 4-carboxy-2,3,6-trifluoro-5
      hydroxyphenoxy group have been prepared for evaluation as possible dUTP
      analogues. They showed a weak ability to displace radiolabelled dUTP from a dUTP
      binding antiserum. The corresponding compounds lacking the three fluorine
      substituents were prepared for comparison.

PMID- 11580196
TI  - Synthesis and binding affinity of a chiral PNA analogue.
AB  - The synthesis of a chiral peptide nucleic acid (PNA), which is composed of N
      aminoethyl-cis-4-nucleobase-L-proline units, was described. The chiral PNA
      monomers containing all four nucleobases (A. T, C and G) were steroselectively
      prepared. The x-ray diffraction data from a single crystal confirmed the
      configuration of a key intermediate. Binding activity of the oligomers with their
      complementary DNA targets was also investigated.

PMID- 11580197
TI  - Synthesis of selenium-derivatized nucleosides and oligonucleotides for X-ray
      crystallography.
AB  - We report here the synthesis of nucleoside and oligonucleotide analogs containing
      selenium, which serves as an anomalous scattering center to enable MAD phase
      determination in nucleotide X-ray crystallography. We have developed a phase
      transfer approach to introduce the selenium functionality in A, C, G, T, and U
      nucleosides at 5'-positions. In the incorporation of the selenium functionality,
      the leaving groups (bromide, mesyl, and tosyl) were readily displaced by sodium
      selenide, sodium diselenide, and sodium methyl selenide with yields higher than
      90%. Selenium-derivatized oligonucleotides have been synthesized via
      phosphoramidite chemistry.

PMID- 11580198
TI  - Synthesis of 2-thiohydantoins and their S-glucosylated derivatives as potential
      antiviral and antitumor agents.
AB  - A series of 3-alkyl-5-((Z))-arylidene-2-thiohydantoins 4a-1 were synthesized from
      the direct condensation of the aromatic aldehydes with 3-alkyl-2-thiohydantoins
      3a-c, which in turn were prepared from the reaction of glycine (1) and alkyl
      isothiocyanates 2a-c. The alkylation of 4a-1 with methylthioethyl chloride gave 5
      ((Z))-arylidene-3-alkyl-S-(2-methylthioethyl)-2-thiohydantoins 5a-e. S
      Glucosylation took place on the reaction of 4a-1 with 2,3,4,6-tetra-O-acetyl
      alpha-D-glucopyranosyl bromide under anhydrous alkaline conditions. These
      structures have been confirmed from a model study of the coupling of 4a with
      methylthioethyl chloride and alpha-D-glucose pentaacetate, respectively under
      Lewis acid conditions.

PMID- 11580199
TI  - Role and distribution of retinoic acid during CNS development.
AB  - Retinoic acid (RA), the biologically active derivative of vitamin A, induces a
      variety of embryonal carcinoma and neuroblastoma cell lines to differentiate into
      neurons. The molecular events underlying this process are reviewed with a view to
      determining whether these data can lead to a better understanding of the normal
      process of neuronal differentiation during development. Several transcription
      factors, intracellular signaling molecules, cytoplasmic proteins, and
      extracellular molecules are shown to be necessary and sufficient for RA-induced
      differentiation. The evidence that RA is an endogenous component of the
      developing central nervous system (CNS) is then reviewed, data which include high
      pressure liquid chromotography (HPLC) measurements, reporter systems and the
      distribution of the enzymes that synthesize RA. The latter is particularly
      relevant to whether RA signals in a paracrine fashion on adjacent tissues or
      whether it acts in an autocrine manner on cells that synthesize it. It seems that
      a paracrine system may operate to begin early patterning events within the
      developing CNS from adjacent somites and later within the CNS itself to induce
      subsets of neurons. The distribution of retinoid-binding proteins, retinoid
      receptors, and RA-synthesizing enzymes is described as well as the effects of
      knockouts of these genes. Finally, the effects of a deficiency and an excess of
      RA on the developing CNS are described from the point of view of patterning the
      CNS, where it seems that the hindbrain is the most susceptible part of the CNS to
      altered levels of RA or RA receptors and also from the point of view of neuronal
      differentiation where, as in the case of embryonal carcinoma (EC) cells, RA
      promotes neuronal differentiation. The crucial roles played by certain genes,
      particularly the Hox genes in RA-induced patterning processes, are also
      emphasized.

PMID- 11580200
TI  - The biology of cortical granules.
AB  - An egg-that took weeks to months to make in the adult-can be extraordinarily
      transformed within minutes during its fertilization. This review will focus on
      the molecular biology of the specialized secretory vesicles of fertilization, the
      cortical granules. We will discuss their role in the fertilization process, their
      contents, how they are made, and the molecular mechanisms that regulate their
      secretion at fertilization. This population of secretory vesicles has inherent
      interest for our understanding of the fertilization process. In addition, they
      have import because they enhance our understanding of the basic processes of
      secretory vesicle construction and regulation, since oocytes across species
      utilize this vesicle type. Here, we examine diverse animals in a comparative
      approach to help us understand how these vesicles function throughout phylogeny
      and to establish conserved themes of function.

PMID- 11580201
TI  - Acetylcholinesterase genes in the nematode Caenorhabditis elegans.
AB  - Acetylcholinesterase (AChE, EC 3.1.1.7) is responsible for the termination of
      cholinergic nerve transmission. It is the target of organophosphates and
      carbamates, two types of chemical pesticides being used extensively in
      agriculture and veterinary medicine against insects and nematodes. Whereas there
      is usually one single gene encoding AChE in insects, nematodes are one of the
      rare phyla where multiple ace genes have been unambiguously identified. We have
      taken advantage of the nematode Caenorhabditis elegans model to identify the four
      genes encoding AChE in this species. Two genes, ace-1 and ace-2, encode two major
      AChEs with different pharmacological properties and tissue repartition: ace-1 is
      expressed in muscle cells and a few neurons, whereas ace-2 is mainly expressed in
      motoneurons. ace-3 represents a minor proportion of the total AChE activity and
      is expressed only in a few cells, but it is able to sustain double null mutants
      ace-1; ace-2. It is resistant to usual cholinesterase inhibitors. ace-4 was
      transcribed but the corresponding enzyme was not detected in vivo.

PMID- 11580202
TI  - Reciprocal regulation of endothelin-1 and nitric oxide: relevance in the
      physiology and pathology of the cardiovascular system.
AB  - The endothelium plays a crucial role in the regulation of cardiovascular
      structure and function by releasing several mediators in response to biochemical
      and physical stimuli. These mediators are grouped into two classes: (1)
      endothelium-derived constricting factors (EDCFs) and (2) endothelium-derived
      relaxing factors (EDRFs), the roles of which are considered to be detrimental and
      beneficial, respectively. Endothelin-1 (ET-1) and nitric oxide (NO) are the
      prototypes of EDCFs and EDRFs, respectively, and their effects on the
      cardiovascular system have been studied in depth. Numerous conditions
      characterized by an impaired availability of NO have been found to be associated
      with enhanced synthesis of ET-1, and vice versa, thereby suggesting that these
      two factors have a reciprocal regulation. Experimental studies have provided
      evidence that ET-1 may exert a bidirectional effect by either enhancing NO
      production via ETB receptors located in endothelial cells or blunting it via ETA
      receptors prevalently located in the vascular smooth muscle cells. Conversely, NO
      was found to inhibit ET-1 synthesis in different cell types. In vitro and in vivo
      studies have started to unravel the molecular mechanisms involved in this complex
      interaction. It has been clarified that several factors affect in opposite
      directions the transcription of preproET-1 and NO-synthase genes, nuclear factor
      KB and peroxisome proliferator-activated receptors playing a key role in these
      regulatory mechanisms. ET-1 and NO interplay seems to have a great relevance in
      the physiological regulation of vascular tone and blood pressure, as well as in
      vascular remodeling. Moreover, an imbalance between ET-1 and NO systems may
      underly the mechanisms involved in the pathogenesis of systemic and pulmonary
      hypertension and atherosclerosis.

PMID- 11580203
TI  - The roles of receptor-associated protein (RAP) as a molecular chaperone for
      members of the LDL receptor family.
AB  - Members of the LDL receptor family mediate endocytosis and signal transduction of
      many extracellular ligands which participate in lipoprotein metabolism, protease
      regulation, embryonic development, and the pathogenesis of disease (e.g.,
      Alzheimer's disease). Structurally, these receptors share common motifs and
      modules that are highlighted with clusters of cysteine-rich ligand-binding
      repeats. Perhaps, the most significant feature that is shared by members of the
      LDL receptor family is the ability of a 39-kDa receptor-associated protein (RAP)
      to universally inhibit ligand interaction with these receptors. Under
      physiological conditions, RAP serves as a molecular chaperone/escort protein for
      these receptors to prevent premature interaction of ligands with the receptors
      and thereby ensures their safe passage through the secretory pathway. In
      addition, RAP promotes the proper folding of these receptors, a function that is
      likely independent from its ability to inhibit ligand binding. The molecular
      mechanisms underlying these functions of RAP, as well as the molecular
      determinants that contribute to RAP-receptor interaction will be discussed in
      this review. Elucidation of these mechanisms should help to clarify how a
      specialized chaperone promotes the biogenesis of LDL receptor family members, and
      may provide insights into how the expression and function of these receptors can
      be regulated via the expression of RAP under pathological states.

PMID- 11580204
TI  - Genetic regulation of preimplantation embryo survival.
AB  - Mammalian embryonic death is the most common outcome of fertilization. This
      review focuses on the recent advances concerning genetic regulation of
      preimplantation embryo survival. The predominant role of the Ped(preimplantation
      embryo development) gene, which regulates fast or slow cleavage of
      preimplantation mouse embryos, and its implication on embryo survival are
      discussed. Recent morphological and biochemical observations suggested that
      programmed cell death was an essential mechanism in preimplantation embryo
      fragmentation and survival, thus leading to original investigations on apoptosis
      and apoptosis-related genes. Other genes, transcripts, or proteins seem to be
      involved in embryo development and control of survival. In particular, the role
      of heat shock proteins (HSP), telomerase activity (human telomerase catalytic
      subunit hTCS), and the developmental significance of regulatory protein
      polarization (leptin, STAT 3) in preimplantation embryos are discussed.

PMID- 11580205
TI  - Basement membrane and beta amyloid fibrillogenesis in Alzheimer's disease.
AB  - High-resolution ultrastructural and immunohistochemical studies revealed that in
      situ beta amyloid fibrils of Alzheimer's disease were made up of a core
      consisting of a solid column of amyloid P component (AP) and associated
      chondroitin sulfate proteoglycan, and a heparan sulfate proteoglycan surface
      layer with externally associated fine filaments of beta protein. The main body of
      beta amyloid fibrils closely resembled that of microfibrils. Abundant
      microfibrils were reported to be present at the basement membrane of capillaries
      with "leaky" blood-urine or blood-air barriers. Similarly, abundant microfibril
      like beta amyloid fibrils are formed at the microvascular basement membrane in
      cerebrovascular amyloid angiopathy with altered blood-brain barrier. Since AP is
      an indispensable major component of microfibrils and microfibril-like structures,
      the formation of microfibrils may depend on, among other factors, the
      availability of AP. Thus, in beta amyloid fibrillogenesis fibrils may be built
      around AP which continuously leaks out from circulation into vascular basement
      membrane, and beta amyloid fibrils may be regarded as pathologically altered
      basement membrane-associated microfibrils. With no source of AP around them,
      senile plaque fibrils may also be derived from perivascular amyloid.

PMID- 11580206
TI  - Regulation of microtubule-associated proteins.
AB  - Microtubule-associated proteins (MAPs) function to regulate the assembly dynamics
      and organization of microtubule polymers. Upstream regulation of MAP activities
      is the major mechanism used by cells to modify and control microtubule assembly
      and organization. This review summarizes the functional activities of MAPs found
      in animal cells and discusses how these MAPs are regulated. Mechanisms
      controlling gene expression, isoform-specific expression, protein localization,
      phosphorylation, and degradation are discussed. Additional regulatory mechanisms
      include synergy or competition between MAPs and the activities of cofactors or
      binding partners. For each MAP it is likely that regulation in vivo reflects a
      composite of multiple regulatory mechanisms.

PMID- 11580207
TI  - Dynein motors of the Chlamydomonas flagellum.
AB  - Chlamydomonas is a biflagellate unicellular green alga that has proven especially
      amenable for the analysis of microtubule (MT)-based molecular motors, notably
      dyneins. These enzymes form the inner and outer arms of the flagellum and are
      also required for intraflagellar transport. Dyneins have masses of approximately
      1-2 MDa and consist of up to 15 different polypeptides. Nucleotide
      binding/hydrolysis and MT motor activity are associated with the heavy chains,
      and we detail here our current model for the substructural organization of these
      approximately 520-kDa proteins. The remaining polypeptides play a variety of
      roles in dynein function, including attachment of the motor to cargo, regulation
      of motor activity in response to specific inputs, and their necessity for the
      assembly and/or stability of the entire complex. The combination of genetic,
      physiological, structural, and biochemical approaches has made the Chlamydomonas
      flagellum a very powerful model system in which to dissect the function of these
      fascinating molecular motors.

PMID- 11580208
TI  - The antisecretory factor: synthesis, anatomical and cellular distribution, and
      biological action in experimental and clinical studies.
AB  - The antisecretory factor (AF) is a 41-kDa protein that provides protection
      against diarrheal diseases and intestinal inflammation. Its cDNA has been cloned
      and sequenced. AF is highly potent, with 10(-12) mol of recombinant AF being
      sufficient to counteract experimentally induced diarrhea in rat. The
      antisecretory activity is exerted by a peptide located between positions 35 and
      50 of the AF sequence. Synthetic peptides based on this sequence are promising
      candidates for drugs to counteract intestinal hypersecretion, as well as
      imbalances of fluid transport in other body compartments. AF probably exerts its
      effects via nerves; AF immediately and potently inhibits ion transport across
      isolated nerve membranes from Deiters' cells. Immunocytochemistry has shown that
      AF is present in most tissues in the body, and in situ nucleic acid hybridization
      has shown that cells that store AF are also capable of AF synthesis. The
      endogenous plasma level of AF is increased by enterotoxins and by certain food
      constituents such as hydrothermally processed cereals. These cereals
      significantly improve clinical performance in patients suffering from
      inflammatory bowel diseases. AF-enhancing food also protects domestic animals
      against diarrheal diseases, and such feed has been used successfully in Swedish
      swine farming for the past 10 years. Increased understanding of AF action might
      result in expanded clinical applications and confirm that AF is an important
      regulator of homeostasis.

PMID- 11580209
TI  - Structure and function of photoreceptor and second-order cell mosaics in the
      retina of Xenopus.
AB  - The structure, physiology, synaptology, and neurochemistry of photoreceptors and
      second-order (horizontal and bipolar) cells of Xenopus laevis retina is reviewed.
      Rods represent 53% of the photoreceptors; the majority (97%) are green light
      sensitive. Cones belong to large long-wavelength-sensitive (86%), large short
      wavelength-sensitive (10%), and miniature ultraviolet wavelength-sensitive (4%)
      groups. Photoreceptors release glutamate tonically in darkness, hyperpolarize
      upon light stimulation and their transmitter release decreases. Photoreceptors
      form ribbon synapses with second-order cells where postsynaptic elements are
      organized into triads. Their overall adaptational status is regulated by ambient
      light conditions and set by the extracellular dopamine concentration. The
      activity of photoreceptors is under circadian control and is independent of the
      central body clock. Bipolar cell density is about 6000 cells/mm2 They receive
      mixed inputs from rods and cones. Some bipolar cell types violate the rule of ON
      OFF segregation, giving off terminal branches in both sublayers of the inner
      plexiform layer. The majority of them contain glutamate, a small fraction is GABA
      positive and accumulates serotonin. Luminosity-type horizontal cells are more
      frequent (approximately 1,000 cells/mm2) than chromaticity cells (approximately
      450 cells/mm2). The dendritic field size of the latter type was threefold bigger
      than that of the former. Luminosity cells contact all photoreceptor types,
      whereas chromatic cells receive their inputs from the short-wavelength-sensitive
      cones and rods. Luminosity cells are involved in generating depolarizing
      responses in chromatic horizontal cells by red light stimulation which form
      multiple synapses with blue-light-sensitive cones. Calculations indicate that
      convergence ratios in Xenopus are similar to those in central retinal regions of
      mammals, predicting comparable spatial resolution.

PMID- 11580211
TI  - Isolation and replication of rabies virus in C6 rat glioma cells (clone CCL-107).
AB  - The susceptibility of the C6 rat glioma cell line (ATCC; CCL-107) to rabies virus
      was characterized. The kinetics of infection performed with a fixed and a wild
      strain (from an infected cow) of rabies virus was monitored by direct
      immunofluorescence. Fluorescent cytoplasmic bodies were readily observed by UV
      microscopy from 24 hours post-infection (hpi) onwards. The ability of C6 to
      produce rabies infective virion particles was confirmed by determining the viral
      titres present in the supernatants of infected cultures, by both BHK-21 cell
      infection and mice inoculation. C6 cells produced similar viral titres to those
      produced by BHK-21 for both strains used. In addition, the yield of rabies
      glycoprotein was assessed by ELISA. In general, BHK-21 and C6 cells infected
      either by PV or with the wild rabies strain produced similar amounts of rabies
      glycoprotein. At 96 hpi, however, when the glycoprotein production peaked, BHK-21
      infected with the wild strain produced significantly higher amounts of
      glycoprotein than C6. Subsequently, the optimal conditions for isolation of wild
      rabies virus strains from C6 cells were established and these proved to be as
      sensitive as NA cells in detecting 10 wild rabies samples. Due to the high
      sensitivity exhibited, C6 rat glioma cells present a new and useful system for
      rabies virus investigation.

PMID- 11580210
TI  - Validation of the sterilization procedure of allogeneic avital bone transplants
      using peracetic acid-ethanol.
AB  - Different procedures are available to inactivate bacteria and fungi, including
      their spores, as well as viruses in human bone transplants. The most efficient
      methods are considered to be gamma irradiation and thermal inactivation as well
      as chemical sterilization methods like the peracetic acid-ethanol treatment
      (PES). Following national and international standards or draft standards, the
      antimicrobial effectiveness of this procedure was evaluated. Due to the
      standardizable size as well as the clinical relevance, defatted human spongiosa
      cuboids (15x15x15 mm) served as model system. After treatment with PES for 2 and
      4 hours, respectively, the titre of living micro-organisms was determined in the
      supernatant and the cuboid. A reduction in the titre of viable micro-organisms
      below the detection level (reduction factor >5 log10) was already achieved after
      an incubation time of 2 hours (Staphylococcus aureus, Enterococcus faecium,
      Pseudomonas aeruginosa, Bacillus subtilis, Clostridium sporogenes, Mycobacterium
      terrae, Candida albicans as well as spores of Bacillus subtilis). No viable micro
      organisms could be detected in any of the PES-treated test cuboids. Spores of
      Aspergillus niger were also completely inactivated. The PES procedure proved to
      be a reliable method for the sterilization of human bone transplants derived from
      spongiosa.

PMID- 11580212
TI  - Enhanced efficacy of anti-D immunoglobulin for treating ITP is not explained by
      higher immunoglobulin polymer content.
AB  - Several reports have suggested that low dose anti-D immunoglobulin is superior to
      high dose immunoglobulin for treatment of idiopathic thrombocytopenia purpura
      (ITP). However, some findings suggest that it is not the anti-D activity per se
      that is responsible for efficacy for treatment of ITP with anti-D immunoglobulin.
      Amongst alternative explanations for the mechanism of action is a relatively
      higher immunoglobulin polymer content of anti-D compared to other immunoglobulin
      products, which is more efficient in causing reticuloendothelial Fc receptor
      blockade. In order to investigate this we have evaluated the polymeric IgG
      content of anti-D and other immunoglobulin products. Different products showed
      considerable variation in immunoglobulin polymer content. There was no clear
      correlation between aggregate or dimer content and product type and anti-D as a
      class of product did not contain higher amounts of either dimer or aggregate
      compared to other products. Some manufacturers' products increased in polymer
      content on storage, but others did not show this effect. Therefore, higher
      immunoglobulin dimer and/or aggregate content cannot explain the increased
      efficacy of anti-D immunoglobulin for treatment of ITP. The role of polymeric Ig
      in efficacy for treatment of ITP is unclear.

PMID- 11580213
TI  - A quantitative analysis for the ADP-ribosylation activity of pertussis toxin: an
      enzymatic-HPLC coupled assay applicable to formulated whole cell and acellular
      pertussis vaccine products.
AB  - The majority of the biological effects of pertussis toxin (PT) are the result of
      a toxin-catalyzed transfer of an adenosine diphosphate-ribose (ADP-ribose) moiety
      from NAD(+)to the alpha-subunits of a subset of signal-transducing guanine
      nucleotide-binding proteins (G-proteins). This generally leads to an uncoupling
      of the modified G-protein from the corresponding receptor and the loss of
      effector regulation. This assay is based on the PT S1 subunit enzymatic transfer
      of ADP-ribose from NAD to the cysteine moiety of a fluorescent tagged synthetic
      peptide homologous to the 20 amino acid residue carboxyl-terminal sequence of the
      alpha-subunit of the G(i3)protein. The tagged peptide and the ADP-ribosylated
      product were characterized by HPLC/MS and MS/MS for structure confirmation.
      Quantitation of this characterized ADP-ribosylated fluorescently tagged peptide
      was by HPLC fluorescence using Standard Addition methodology. The assay was
      linear over a five hr incubation period at 20 degrees C at PT concentrations
      between 0.0625 and 4.0 microg/ml and the sensitivity of the assay could be
      increased several fold by increasing the incubation time to 24 h. Purified S1
      subunit of PT exhibited 68.1+/-10.1% of the activity of the intact toxin on a
      molar basis, whereas the pertussis toxin B oligomer, the genetically engineered
      toxoid, (PT-9K/129G), and several of the other components of the Bordetella
      pertussis organism possessed little (<0.6%) or no detectable ribosylation
      activity. Commonly used pertussis vaccine reference materials, US PV Lot #11, BRP
      PV 66/303, and BRP PV 88/522, were assayed by this method against Bordetella
      pertussis Toxin Standard 90/518 and demonstrated to contain, respectively,
      0.323+/-0.007, 0.682+/-0.045, and 0.757+/-0.006 microg PT/ml (Mean+/-SEM) or in
      terms of microg/vial: 3.63, 4.09 and 4.54, respectively. A survey of several
      multivalent pertussis vaccine products formulated with both whole cell as well as
      acellular components indicated that products possessed a wide range of
      ribosylation activities. The pertussis toxin S1 subunit catalyzed ADP-
      ribosylation of the FAC-Galpha(i3)C20 peptide substrate and its subsequent
      quantitation by HPLC was demonstrated to be a sensitive and quantitative method
      for measuring intrinsic pertussis toxin activity. This methodology not only has
      the potential to be an alternative physicochemical method to replace existing
      bioassay methodology, but has the added advantage of being a universal method
      applicable to the assay of pertussis toxin in both whole cell and acellular
      vaccines as well as bulk and final formulated vaccine products. Acceptance of
      this method by regulatory agencies and industry as a credible alternative to
      existing methods would, however, require validation in an international
      collaborative study against the widely accepted bioassay methods.

PMID- 11580214
TI  - The Second International Standard for somatropin (recombinant DNA-derived human
      growth hormone): preparation and calibration in an international collaborative
      study.
AB  - A preparation of somatropin (recombinant DNA-derived human growth hormone) was
      prepared as lyophilised ampoules according to WHO procedures for international
      biological standards. The candidate preparation (98/574) was evaluated in an
      international collaborative study (16 laboratories, nine countries), with the
      following aims: (i) to determine the suitability of the preparation to serve as
      the International Standard for somatropin by studying its performance in the
      current range of physico-chemical and biological assay methods employed for
      somatropin; (ii) to assign a content in terms of the existing (first)
      International Standard for somatropin, using the currently recognised assay
      procedure (Size Exclusion High Performance Liquid Chromatography, SE HPLC); (iii)
      to confirm the specific biological activity of the candidate preparation; (iv) to
      confirm the stability of the candidate preparation. On the basis of the
      collaborative study WHO agreed that: the preparation in ampoules coded 98/574 is
      suitable to serve as the next WHO International Standard for somatropin; the
      preparation in ampoules coded 98/574 should be established as the second
      International Standard for somatropin, with a defined ampoule content of 1.95 mg
      total somatropin plus somatropin-related proteins per ampoule; the specific
      activity of the preparation should be defined as 3.0 IU/mg somatropin.

PMID- 11580215
TI  - Calibration of replacement international standard and European Pharmacopoeia
      Biological Reference Preparation for Diphtheria Toxoid, Adsorbed.
AB  - We report here the characterisation of a preparation of diphtheria toxoid,
      adsorbed, and its calibration by twenty laboratories in fourteen countries in
      terms of the Second International Standard (I.S.) for Diphtheria Toxoid,
      Adsorbed, coded sample A (DIXA) using the established World Health Organisation
      (WHO)/European Pharmacopoeia (Ph Eur) challenge methods. The replacement standard
      preparation was found to have a unitage of 160 IU/ampoule on the basis of its
      calibration by in vivo bioassay. Stability was assessed within the collaborative
      study, and as part of candidate characterisation. Results suggest that the
      replacement standard will have satisfactory stability. This study also provided
      an opportunity to investigate serology as alternative to in vivo bioassay for
      potency testing of diphtheria vaccines. Six laboratories participated by
      performing serology according to in-house protocol. The calibration of the
      replacement standard in a mouse Vero cell assay gave a significantly higher
      results than in the established WHO/Ph Eur methods. Based on the results of this
      study and with the agreement of participants, the candidate standard was
      established as the Third International Standard for Diphtheria Toxoid, Adsorbed
      (coded 98/560) by the WHO Expert Committee of Biological Standardization in
      October 1999. The same preparation was also established as the second Ph Eur
      Biological Reference Preparation (Ph Eur BRP, batch no. 3) by the Steering
      Committee of the Biological Standardisation Programme of the European Directorate
      for the Quality of Medicines and approved by the European Pharmacopoeia
      Commission.

PMID- 11580216
TI  - Residual DNA quantification in clinical batches of BBG2Na, a recombinant subunit
      vaccine against human respiratory syncytial virus.
AB  - BBG2Na, a well-defined recombinant protein produced in Escherichia coli, is a
      promising human respiratory syncytial virus subunit vaccine candidate. This study
      describes the quantification of residual DNA in large scale batches used in phase
      I to III clinical trials. Two different analytical methods were developed and
      applied on five different final bulks of Drug Substance and their associated in
      process control samples, namely a chemiluminescent hybridisation assay and the
      total DNA Threshold System assay. These two complementary methods demonstrated
      the clearance of residual DNA during the downstream purification process. The
      amount of residual DNA found in the final bulks was below 20 pg of DNA per 300
      microg BBG2Na, the highest tested clinical dose of antigen. This is very low
      level of residual DNA for a recombinant subunit vaccine produced in a bacteria
      and contribute to make for BBG2Na a well-characterised biopharmaceutical. This
      study also provides data concerning the validation of the hybridisation dot blot
      assay and the total DNA Threshold(trade mark)assay.

PMID- 11580217
TI  - Third International Standard for pertussis vaccine: international confirmation
      study of activity of British Standard for pertussis vaccine, coded 66/303.
AB  - The first British Standard (BS) (Code 66/303) for pertussis whole cell vaccine
      was prepared from the same suspension of Bordetella pertussis as the now
      exhausted Second International Standard for Pertussis Vaccine (2ndIS). The BS and
      the 2ndIS were compared and calibrated in a previous international study. This
      report describes a small international study, which included the BS, the 1stIS
      and the 2ndIS so that the present relationship of these preparations to one
      another could be assessed. The results of this study show that the relationship
      of the BS to the 1stIS is consistent with its established unitage of 46 IU per
      ampoule. The results further show that the potency of the BS is broadly
      consistent with that of the 2ndIS and that the BS has not lost activity relative
      to the 2ndIS (from which it was previously found to be indistinguishable). Based
      on its original calibration and supported by the results of this present study,
      the BS has been established as the Third International Standard for Pertussis
      Vaccine, with an assigned unitage of 46 IU per ampoule.

PMID- 11580218
TI  - International collaborative study: evaluation of proposed International Reference
      Reagent of pertussis antiserum (mouse) 97/642.
AB  - A freeze dried preparation of mouse serum in vials coded 97/642 containing
      antibodies to five pertussis antigens [pertussis toxin (PT), filamentous
      hemagglutinin (FHA), pertactin (PRN), fimbriae type 2 and 3 (Fim 2 and 3)] has
      been assessed for its suitability as an international reference reagent in an
      international collaborative study by thirteen laboratories in nine countries.
      This serum has been compared with U.S. Standard Pertussis Antiserum (mouse) Lot
      No. 1 (US Lot 1), which has been in use since 1995, for antibodies for each
      antigen. Calibration of the proposed International Reference Reagent of Pertussis
      Antiserum (pIRR) in terms of US Lot 1 gives results which are broadly consistent
      between laboratories for antibodies to each antigen, although the between
      laboratory differences are larger than those seen for comparison of identical
      sera. Calibration of two positive control sera in terms of the pIRR gave similar
      between laboratory variability of estimates to that obtained when the same sera
      were calibrated in terms of US Lot 1. Overall continuity of estimates is
      maintained if units are assigned to the pIRR based on its calibration in terms of
      US Lot 1 in this study. Data presently available indicate that the pIRR is
      sufficiently stable to serve as a reference reagent. It was therefore
      recommended, with the agreement of all participants, that the preparation in
      vials coded 97/642 be established as the First International Reference Reagent
      for Pertussis Antiserum, mouse, with assigned unitages 16 units of anti-PT per
      vial, 143 units of anti-FHA per vial and 30 units of anti-PRN per vial based on
      its calibration in terms of US Lot 1. These unitages are also consistent with
      calibration of 97/642 in terms of the Japanese preparations JNIH-11 for anti-FHA
      and of JNIH-12 for anti-PT. Purified antigens for Fim 2 and Fim 3 are not readily
      available and an arbitrary value of 32 units per vial is suggested for anti-Fim 2
      and 3 mixture. These recommendations were agreed by the Expert Committee on
      Biological Standardization of the World Health Organization.

PMID- 11580219
TI  - Sarcoidosis and IL18.

PMID- 11580220
TI  - T cell receptor Vbeta repertoire expression reflects gastric carcinoma
      progression.
AB  - Analysis of TCR beta-chain complementarity-determining region size gives an
      indication of the T cell immune response. We examined CD4+ and CD8+ subgroups of
      T cells in the peripheral blood (PBL), benign gastric mucosa, and tumor (TIL)
      lymphocytes of 12 patients with primary gastric carcinomas of both intestinal and
      diffuse types. The average number of expanded clones in each compartment,
      expressed by the 24 families of the TCRVbeta repertoire, was analyzed according
      to tumor histological type, maximal invasive depth, and lymph node metastases.
      Fewer clones were expressed by the PBL in the cases with lymph node metastases
      than in those without (CD4+ P = 0.00017, CD8+ P = 0.016). Fewer CD8+ clones were
      expressed by the PBL in the cases with full thickness tumor infiltration than in
      those involving only the mucosa and submucosa (P = 0.05). The CD8+ TIL showed
      significantly fewer clones in the diffuse-type carcinoma than in the intestinal
      type (P = 0.046).

PMID- 11580221
TI  - Leptin does not influence the IgE response to ovalbumin in mice.
AB  - Leptin is important for maintenance of the body's energy homeostasis and it also
      increases Th1 and suppresses Th2 cytokine production. We have investigated the
      effect of leptin on the allergic immune response to the model allergen ovalbumin
      (OA) by using the popliteal lymph node assay (PLNA) and serum antibody
      determination in mice. Mice were injected with either leptin i.v. plus OA in one
      hind footpad, or leptin or OA alone. A booster dose of leptin was given twice and
      of OA once and the animals were exsanguinated on experimental day 19 when the
      PLNs also were removed. End-point measurements were serum levels of IgE, IgG1,
      and IgG2a anti-OA and weight and cell number of the excised PLNs. Leptin given
      i.v. with the protocol employed altered neither the cellular PLN response nor the
      specific serum IgE, IgG1, or IgG2a anti-OA levels compared with the group given
      OA without leptin. Our data indicate that systemic administration of leptin
      neither suppresses nor enhances the Th2-dependent antibody responses in the
      present mouse model.

PMID- 11580222
TI  - Elevated expression of interleukin-18 in the granulomatous lesions of muscular
      sarcoidosis.
AB  - In an attempt to understand the role of interleukin-18 (IL-18) in the
      pathogenesis of sarcoidosis, we examined the expression of IL-18 in normal muscle
      and in muscle biopsies from six patients with muscular sarcoidosis. Western blot
      analysis demonstrated that IL-18 was identified only in homogenates of
      granulomatous muscle tissues, but not in normal muscle tissue homogenates. By
      immunohistochemistry, strongly IL-18-positive cells were distributed
      predominantly at the boundary zone of the granulomas. They were recognized as
      activated macrophages by double staining with anti-CD68. Epithelioid cells showed
      only faint reactivity. Serum IL-18 levels of patients with sarcoidosis were
      significantly increased compared to those of healthy volunteers. Unlike protein
      expression, IL-18 mRNA expression was detected even in normal muscles. Our
      results coupled with those of previous investigations demonstrating activity of
      IL-18 in inducing interferon-gamma production suggest a significant role of IL-18
      in the pathogenesis of sarcoidosis.

PMID- 11580223
TI  - Hybrid IgA2/IgG1 antibodies with tailor-made effector functions.
AB  - Immunoglobulin (Ig) A and IgG are the principal immune effector molecules at
      mucosal surfaces and in blood, respectively. Mucosal IgA is polymeric and bound
      to secretory component, whereas serum IgG is monomeric. We have now produced
      IgA2/IgG1 hybrid antibodies that combine the properties of IgA and IgG.
      Antibodies with Calpha3 at the end of the IgG H chain resemble IgA and form
      polymers with J chain that bind the polymeric Ig receptor. Like IgG, the hybrid
      proteins activated complement and bound FcgammaRI and protein A. Though the
      hybrid proteins contained both Cgamma2 and Cgamma3, they have a short in vivo
      half-life. Surprisingly, this decreased half-life correlated with a higher
      avidity than that of IgG for murine FcRn. Interestingly, antibodies with Calpha1
      replacing Cgamma1 were resistant to extremes of pH, suggesting that Calpha1
      increases antibody stability. These results provide insights into engineering
      antibodies with novel combinations of effector functions.

PMID- 11580224
TI  - Bacteremia associated with live attenuated chi8110 Salmonella enterica serovar
      Typhi ISP1820 in healthy adult volunteers.
AB  - Live attenuated chi8110 Salmonella enterica serovar Typhi ISP1820 vaccine was
      given in a dose-escalation trial to healthy, adult volunteers. Positive stool and
      blood cultures were noted, but limited, as were immune responses measured by
      ELISA and ELISPOT. Only volunteers with bacteremia developed immune responses;
      however, no symptoms were associated with bacteremia. The vaccine was
      insufficiently immunogenic for use as a vaccine. It is possible that reduced
      survival in the gut and reduced immunogenicity may have been due to the thawing
      of frozen inocula immediately prior to use.

PMID- 11580225
TI  - Fibrillarin and other snoRNP proteins are targets of autoantibodies in xenobiotic
      induced autoimmunity.
AB  - Exposure of SJL/J mice to mercury induces an anti-nucleolar autoantibody
      response. The predominant target is fibrillarin, a 34-kDa component of the small
      nucleolar ribonucleoprotein particles (snoRNP), but other proteins are also
      recognized. To characterize these proteins, monoclonal IgG anti-nucleolar
      antibodies were produced from HgC12-treated SJL/J mice. One monoclonal, 17C12,
      recognized fibrillarin, while two others, 7G3 and 6G10, were found to
      immunoprecipitate snoRNP particles but not fibrillarin. Antibody 6G10 gave a
      nucleolar immunofluorescence pattern in human, murine, and amphibian cells, but
      was negative in immunoblot. The 7G3 monoclone reacted with a 60-kDa protein
      conserved in human and murine, but not amphibian, cell lines. The 7G3 and 6G10
      antigens and fibrillarin colocalized to the nucleolus and Cajal bodies in
      interphase cells and decorated metaphase chromosomes. These studies suggest that
      the mercury-induced anti-nucleolar antibody response targets other protein
      components of the snoRNP particles in addition to fibrillarin.

PMID- 11580226
TI  - Dendritic cell vaccination induces cross-reactive cytotoxic T lymphocytes
      specific for wild-type and natural variant human immunodeficiency virus type 1
      epitopes in HLA-A*0201/Kb transgenic mice.
AB  - Dendritic cells (DC) are highly efficient at inducing primary T cell responses.
      Consequently, DC are being investigated for their potential to prevent and/or
      treat human immunodeficiency virus type 1 (HIV-1) infection. In the current
      study, we examined the capacity of DC to elicit CD8+ cytotoxic T lymphocyte (CTL)
      reactivity against an HLA-A*0201-restricted HIV-1 reverse transcriptase (pol)
      epitope (residues 476-484) and two naturally occurring variants. Previous work
      demonstrated that the wild-type pol epitope is recognized by CTLs from HIV-1
      infected individuals, whereas the variant pol epitopes are not, despite binding
      to HLA-A*0201. In agreement with these observations, parenteral administration of
      wild-type pol peptide induced HLA-A*0201-restricted CTL activity in A2Kb
      transgenic mice. In contrast, similar treatment with the two variant pol peptides
      failed to stimulate CTL reactivity, and this lack of immunogenicity correlated
      with reduced peptide:HLA-A*0201 complex stability. However, CTL responses were
      induced in A2Kb transgenic mice upon adoptive transfer of syngeneic bone marrow
      DC pulsed with the variant pol peptides. Furthermore, DC pulsed with the wild
      type pol peptide elicited CTLs that cross-reacted with the variant pol epitopes.
      These results demonstrate that DC effectively expand the T cell repertoire of a
      given epitope to include cross-reactive T cell clonotypes. Accordingly, DC
      vaccination may aid in immune recognition of HIV-1 escape variants by broadening
      the T cell response.

PMID- 11580227
TI  - Cryoprecipitate of patients with cryoglobulinemic glomerulonephritis contains
      molecules of the lectin complement pathway.
AB  - Serological and histological studies were carried out to explore the role of the
      lectin complement pathway in the pathogenesis of cryoglobulinemic
      glomerulonephritis. Sixteen patients with mixed cryoglobulinemia type II with
      glomerulonephritis (GN) were enrolled. All cases had hepatitis C virus (HCV)
      infection. The serum concentration of mannose-binding lectin (MBL) was
      significantly higher in the GN patients than in the normal controls according to
      ELISA (P < 0.01). IgG, IgM, C1q, C4d, HCV envelope antigen, MBL, and MBL
      associated serine protease-1 (MASP-1) could be visualized in the cryoprecipitate
      of the 16 patients by Dot blot assay. Renal biopsy specimens obtained from 3
      patients were examined by immunohistochemistry, and the glomeruli strongly
      stained for IgG, IgM, MBL, MASP-1, C4d, C3c, and C3d in a fringe-like pattern.
      The pattern of HCV constituent deposition was partially fringe-like. The
      complement profiles of the 16 cases were distinctive; briefly, the serum levels
      of C1q, C2, and C3 were reduced, although the levels of circulating regulatory
      proteins (C1-inhibitor, factor H, and factor I) were in the normal range. The
      serum C4 level was significantly reduced. These results indicate that immune
      complex formation involves molecules of the lectin pathway and leads to organ
      damage in cryoglobulinemic glomerulonephritis.

PMID- 11580228
TI  - The N-terminal flanking region of the invariant chain peptide augments the
      immunogenicity of a cryptic "self" epitope from a tumor-associated antigen.
AB  - The N-terminal flanking region of the invariant chain peptide termed CLIP appears
      to have superagonistic properties interacting with the T cell receptor and the
      MHC class II molecule at or near the binding site for the bacterial superantigen
      Staphylococcal enterotoxin B (SEB). The present studies explored the hypothesis
      that the N-terminal segment of CLIP can augment the immunogenicity of cryptic
      "self" tumor-associated antigens. A chimeric construct of an MHC class II binding
      peptide from the c-erb oncogene (Her-2/neu) containing the N-terminal flanking
      region of CLIP elicited potent antitumor activity against a Her-2/neu-positive
      tumor in a rat model system. Comparatively, the unmodified parent peptide was
      ineffective. The induction of effective antitumor immunity, however, required
      presentation of the chimeric peptide construct on irradiated tumor cells or the
      peptide construct in concert with a Her-2/neu MHC class I-restricted peptide from
      Her-2/neu. As revealed by adoptive transfer studies, effective protective
      antitumor immunity in this setting required the CD4 T helper subset.
      Additionally, in vitro analysis revealed that immunization with the parent
      peptide resulted in a weak immune response to the unmodified peptide consisting
      of both type 1 (IL-2, IFN-gamma) and type 2 (IL-4, IL-10) cytokine-producing
      cells analyzed by RT-PCR (qualitative and quantitative) and by limiting dilution
      assay. Comparatively, immunization with the chimeric construct elicited a potent
      immune response to the parent peptide with predominantly type 1 cytokine
      producing cells. Taken together, the results suggest that immunization with the
      chimeric Her-2/neu peptide induced protective antitumor immunity. Associated with
      this immunization strategy was the enhancement of a type 1 cytokine response.

PMID- 11580229
TI  - Analysis of monocyte chemotactic protein-1 production in different major
      histocompatability complex-restricted antigen presentation systems.
AB  - In the present study the production of the CC chemokine monocyte chemotactic
      protein-1 (MCP-1) in several MHC II-restricted antigen presentation systems was
      investigated in vitro. To assess which type of antigen-presenting cell (APC)
      influences MCP-1 production during antigen presentation, cultures enriched for
      different APC populations were prepared and MCP-1 production was determined. Our
      results showed that APCs that effectively induce a T cell response also produce
      elevated amounts of MCP-1. The MCP-1 production is highest in the memory-driven
      secondary response against a single antigen. Despite a massive T cell
      proliferation, low MCP-1 concentrations are found in Con A-induced cultures.
      These results suggest that T cell proliferation alone is not sufficient for MCP-1
      production and that stimulation of the APC during the process of antigen
      presentation results in MCP-1 production. Based on our results and the
      literature, we propose a model for MCP-1 as an enhancer of the adaptive immune
      response.

PMID- 11580230
TI  - Alterations in nitric oxide synthase activity and expression in submandibular
      glands of NOD mice.
AB  - The non-obese diabetic (NOD) mouse model of autoimmune sialadenitis offers the
      possibility of studying the L-arginine/nitric oxide signaling pathway in salivary
      glands in basal and neurotransmitter-stimulated conditions and, thus, of
      analyzing the neural control of the secretory process in the target organ. The
      purpose of this study was to explore putative alterations in the activity and
      expression of nitric oxide synthase (NOS) in submandibular glands of NOD mice in
      relation to parotid glands and unrelated tissues. Here we report that NOD mice
      with incipient signs of secretory dysfunction presented a marked decrease in
      basal and vasoactive intestinal peptide (VIP)-stimulated NOS activity and a
      differential expression of NOS I in submandibular glands compared to control
      BALB/c mice. Similar alterations in NOS I were found in parotid glands but not in
      brain or spleen of NOD mice. No differences between NOD and controls appeared in
      NOS II and NOS III expression in any of the tissues studied.

PMID- 11580231
TI  - Interaction of human papillomavirus type 11 E7 protein with TAP-1 results in the
      reduction of ATP-dependent peptide transport.
AB  - Human papillomaviruses (HPVs) cause benign and malignant epithelial tumors of the
      respiratory and genital mucosa. We previously reported that recurrent respiratory
      papillomas caused by HPV 6/11 express low levels of antibody-detectable TAP-1,
      the protein that transports peptides into the endoplasmic reticulum for assembly
      and presentation by MHC Class I, and that the extent of TAP-1 immunostaining is
      inversely related to the frequency of disease recurrence. We have now determined
      a mechanism for the reduction in TAP-1 detection. Anti-TAP-1 antibody
      immunoprecipitated very low amounts of protein from papilloma cells. However,
      immunoprecipitation of calreticulin, another member of the MHC I assembly
      complex, coprecipitated TAP-1 at levels comparable to those of uninfected cells.
      Immunoprecipitation of an HPV-positive cell line with either anti-TAP-1 or anti
      calreticulin coprecipitated HPV E7 protein. Finally, purified HPV 11 E7 protein
      inhibited ATP-dependent peptide transport in vitro. We propose that the
      interaction of E7 with TAP-1 prevents TAP-1 antibody detection and efficient
      peptide transport, resulting in poor presentation of viral antigen on HPV
      infected cells and thus failure to mount an effective immune-mediated prevention
      of disease recurrence.

PMID- 11580232
TI  - IgG autoantibodies in patients with anti-epiligrin cicatricial pemphigoid
      recognize the G domain of the laminin 5 alpha-subunit.
AB  - Anti-epiligrin cicatricial pemphigoid (AECP) is a mucosal-predominant,
      subepithelial blistering disease characterized by IgG anti-basement membrane
      autoantibodies to laminin 5 (alpha3beta3gamma2). This and prior studies found
      that autoantibodies from most patients recognize the alpha-subunit of this
      laminin isoform. Accordingly, sera from 10 representative patients were tested
      against prokaryotic recombinants of this polypeptide in epitope mapping studies.
      cDNAs spanning the full length of the alpha-subunit were generated by PCR,
      directionally cloned into the pGEX-4T-3 vector, and expressed as glutathione-S
      transferase fusion proteins of appropriate size and immunoreactivity. Sera from 9
      of 10 AECP patients immunoblotted fusion proteins corresponding to subdomains G2,
      G3, G4, and G5 at the carboxyl terminus of the laminin 5 alpha-subunit. Serum
      from 1 patient (and that from normal volunteers) showed no reactivity to any
      fusion proteins; no sera bound recombinant glutathione-S-transferase alone.
      Immunoadsorption of patient sera with fusion proteins corresponding to the G
      domain substantially reduced basement membrane autoantibody titers. IgG from
      patients with this form of cicatricial pemphigoid recognize the portion of
      laminin 5 thought to play a key role in promoting keratinocyte adhesion to
      epidermal basement membrane.

PMID- 11580233
TI  - Systemic immune response in whiplash injury and ankle sprain: elevated IL-6 and
      IL-10.
AB  - Whiplash injury and whiplash-associated disorders (WAD) are significant problems
      of modern society. Numerous attempts have been made to characterize the nature of
      whiplash injury. Whether the immune system is involved during the disease process
      is not known. In a prospective study, using enzyme-linked immunospot (ELISPOT)
      assays, we examined numbers of blood mononuclear cells (MNC) secreting pro- (IFN
      gamma, TNF-alpha, IL-6) and anti-inflammatory (IL-10) cytokines in patients with
      WAD and, for reference, patients with ankle sprain and multiple sclerosis and
      healthy subjects. An immune response reflected by elevated numbers of TNF-alpha-
      and IL-10-secreting blood MNC was observed in patients with WAD examined within 3
      days compared to 14 days after the whiplash injury. The patients with WAD
      examined within 3 days after the injury had also higher numbers of IL-6 and IL-10
      secreting blood MNC compared to healthy subjects. The alterations of cytokine
      profiles observed in WAD were also observed in patients with ankle sprain when
      examined within 3 days after trauma. In contrast, there were no differences for
      cytokine profiles between patients with WAD examined 14 days after the whiplash
      injury and healthy subjects. Relatively minor trauma like WAD and ankle sprain
      are associated with a systemic dysregulation in numbers of cells secreting pro-
      as well as anti-inflammatory cytokines.

PMID- 11580234
TI  - In vitro selection of allosteric ribozymes: theory and experimental validation.
AB  - In vitro selection techniques offer powerful and versatile methods to isolate
      nucleic acid sequences with specific activities from huge libraries. We describe
      an in vitro selection strategy for the de novo selection of allosteric self
      cleaving ribozymes responding to pefloxacin and other quinolone derivatives.
      Within 16 selection cycles, highly sensitive clones responding to drug levels in
      the sub-micromolar range were obtained. The morpholine moiety of the quinolone
      derivatives was required for inhibition of the self-cleavage of the selected
      ribozymes: modifications of the aromatic system were tolerated better than
      modifications of the morpholine ring. We also present a theoretical model that
      analyzes the predicted fraction of ribozymes with a given binding constant and
      cleavage rate recovered after each selection cycle. This model precisely predicts
      the actual experimental values obtained with the selection procedure. It can thus
      be used to determine the optimal conditions for an in vitro selection of an
      allosteric ribozyme with a desired dissociation constant and cleavage rate for a
      given application.

PMID- 11580235
TI  - The protelomerase of the phage-plasmid N15 is responsible for its maintenance in
      linear form.
AB  - The prophage of coliphage N15 is not integrated into the bacterial chromosome but
      exists as a linear plasmid molecule with covalently closed ends. Upon infection
      of an Escherichia coli cell, the phage DNA circularises via cohesive ends. A
      phage-encoded enzyme, protelomerase, then cuts at another site, telRL, and forms
      hairpin ends (telomeres). We demonstrate that this enzyme acts in vivo on
      specific substrates, and show that it is necessary for replication of the linear
      prophage. We show that protelomerase is an end-resolving enzyme responsible for
      processing of replicative intermediates. Removal of protelomerase activity
      resulted in accumulation of replicative intermediates that were found to be
      circular head-to-head dimers. N15 protelomerase and its target site constitute a
      functional unit acting on other replicons independently of other phage genes; a
      mini-F or mini-P1 plasmid carrying this unit replicates as a linear plasmid with
      covalently closed ends. Our results suggest the following model of N15 prophage
      DNA replication. Replication is initiated at an internal ori site located close
      to the left end of plasmid DNA and proceeds bidirectionally. After replication of
      the left telomere, protelomerase cuts this sequence and forms two hairpin loops
      telL. After duplication of the right telomere (telR) the same enzyme resolves
      this sequence producing two linear plasmids. Alternatively, full replication of
      the linear prophage to form a circular head-to-head dimer may precede
      protelomerase-mediated formation of hairpin ends.

PMID- 11580236
TI  - Self-assembly of the amphipathic helix (VHLPPP)8. A mechanism for zein protein
      body formation.
AB  - gamma-Zein, a maize storage protein with an N-terminal proline-rich repetitive
      domain (gamma-ZNPRD), is located at the periphery of protein bodies. This domain
      appears to be indispensable for the aggregation of the protein on the surface of
      the organelle. The peptide (VHLPPP)8, spanning the gamma-ZNPRD, adopts a
      polyproline II (PPII) conformation that gives an amphipathic helix different from
      the alpha-helix. We used atomic force microscopy to study the surface
      organisation of the octamer, and transmission electron microscopy to visualise
      aggregates of the peptide in aqueous solution. We consider two self-assembly
      patterns that take account of the observed features. The micellar one fits best
      with the experimental results presented. Moreover, we found that this peptide has
      properties associated with surfactants, and form micelles in solution. This
      spontaneous amphipathic arrangement of the gamma-ZNPRD suggests a mechanism of
      gamma-zein deposition inside maize protein bodies.

PMID- 11580237
TI  - A recombinant glycine receptor fragment forms homo-oligomers distinct from its
      GABA(A) counterpart.
AB  - The ligand-gated ion channel receptor superfamily includes receptors for glycine,
      GABA, acetylcholine and serotonin. Whereas the acetylcholine and serotonin
      receptors mediate excitory neurotransmissions, both glycine and GABA(A) receptors
      are inhibitory. In this study, a fragment of the human glycine receptor alpha1
      subunit, consisting of residues Ala165-Met291 (numbering based on the precursor
      protein), was hyperexpressed for the first time in Escherichia coli. This
      fragment is highly homologous in sequence to the corresponding fragment of the
      GABA(A) receptor. The recombinant fragment was found to have stable beta-rich
      secondary structure, similar to that found for the homologous GABA(A) receptor
      fragment, and ordered tertiary packing, suggesting a stable structural domain.
      Results from laser scattering studies suggest that the fragment forms trimers in
      solution. In addition, SDS-induced changes in secondary structure were found to
      occur prior to changes in oligomerization status, suggesting that oligomerization
      was secondary structure dependent. A study of quaternary structure using single
      particle analysis electron microscopy (EM) also suggested that the fragment
      formed homo-trimers. One trimer measures approximately 7.5 nm in diameter with a
      central cavity approximately 1.5 nm across. This is the first EM study on a
      single domain of the glycine receptor and the result is in contrast to the
      pentameric assembly of the equivalent GABA(A) receptor fragment reported by us
      earlier. The fact that this fragment alone could form oligomers in vitro suggests
      that amino acid residues within this segment may be involved in the
      oligomerization of the glycine receptor in vivo. Furthermore, the finding that
      two cousin receptor fragments form distinct quaternary structures indicates that
      sequence similarity does not necessarily imply quaternary structure similarity
      and, hence, care must be taken when applying a structure model derived from
      studies of individual receptors to the whole ligand-gated ion channel
      superfamily.

PMID- 11580238
TI  - Crystallographic analysis of Lac repressor bound to natural operator O1.
AB  - Previous structures of Lac repressor bound to DNA used a fully symmetric "ideal"
      operator sequence that is missing the central G-C base-pair present in the three
      natural operator sequences. Here we have determined the X-ray crystal structure
      of a dimeric Lac repressor bound to a 22 base-pair DNA with the natural operator
      O1 sequence and the anti-inducer ONPF, at 4.0 A resolution. The natural operator
      is bent in the same way as the symmetric sequence, due to the binding of the
      hinge helices of the repressor to the minor groove at the central GCGG sequence
      of O1. Comparison of the structures of the repressor bound to the natural and
      symmetric operators shows very similar overall structures, with only slight
      rearrangements of the headpiece domains of the repressor. Analysis of crystals
      with iodinated DNA shows that the operator is uniquely positioned and allows for
      the sequence registration of the DNA relative to the repressor to be determined.
      The kink in the operator is centered between the left half-site and the central G
      C base-pair of O1. Our results are most consistent with a previously proposed
      model in which, relative to the complex with the symmetric operator, the
      repressor accommodates binding to the natural operator sequence by shifting the
      position of the right headpiece by one base-pair step towards the center of O1.

PMID- 11580239
TI  - Energetics, stability, and prediction of transmembrane helices.
AB  - We show that the peptide backbone of an alpha-helix places a severe thermodynamic
      constraint on transmembrane (TM) stability. Neglect of this constraint by
      commonly used hydrophobicity scales underlies the notorious uncertainty of TM
      helix prediction by sliding-window hydropathy plots of membrane protein (MP)
      amino acid sequences. We find that an experiment-based whole-residue hydropathy
      scale (WW scale), which includes the backbone constraint, identifies TM helices
      of membrane proteins with an accuracy greater than 99 %. Furthermore, it
      correctly predicts the minimum hydrophobicity required for stable single-helix TM
      insertion observed in Escherichia coli. In order to improve membrane protein
      topology prediction further, we introduce the augmented WW (aWW) scale, which
      accounts for the energetics of salt-bridge formation. An important issue for
      genomic analysis is the ability of the hydropathy plot method to distinguish
      membrane from soluble proteins. We find that the method falsely predicts 17 to 43
      % of a set of soluble proteins to be MPs, depending upon the hydropathy scale
      used.

PMID- 11580240
TI  - Escherichia coli PriA helicase: fork binding orients the helicase to unwind the
      lagging strand side of arrested replication forks.
AB  - Escherichia coli PriA is a primosome assembly protein with 3' to 5' helicase
      activity whose apparent function is to promote resumption of DNA synthesis
      following replication-fork arrest. Here, we describe how initiation of helicase
      activity on DNA forks is influenced by both fork structure and by single-strand
      DNA-binding protein. PriA could recognize and unwind forked substrates where one
      or both arms were primarily duplex, and PriA required a small (two bases or
      larger) single-stranded gap at the fork in order to initiate unwinding. The
      helicase was most active on substrates with a duplex lagging-strand arm and a
      single-stranded leading-strand arm. On this substrate, PriA was capable of
      translocating on either the leading or lagging strands to unwind the duplex ahead
      of the fork or the lagging-strand duplex, respectively. Fork-specific binding
      apparently orients the helicase domain to unwind the lagging-strand duplex.
      Binding of single-strand-binding protein to forked templates could inhibit
      unwinding of the duplex ahead of the fork but not unwinding of the lagging-strand
      duplex or translocation on the lagging-strand template. While single-strand
      binding protein could inhibit binding of PriA to the minimal, unforked DNA
      substrates, it could not inhibit PriA binding to forked substrates. In the cell,
      single-strand-binding protein and fork structure may direct PriA helicase to
      translocate along the lagging-strand template of forked structures such that the
      primosome is specifically assembled on that DNA strand.

PMID- 11580241
TI  - Quantitative analysis of DNA binding by the Escherichia coli arginine repressor.
AB  - Allosteric activation of the hexameric arginine repressor (ArgR) for specific
      operator DNA binding appears to involve alteration in its quaternary structure.
      Current models for activation include subunit assembly and/or domain
      rearrangements in response to binding of the coeffector l-arginine. To
      investigate the molecular basis for ArgR operator interactions, we have carried
      out a series of quantitative analyses of ArgR subunit assembly and of the
      affinity, stoichiometry, cooperativity, and l-arginine- and DNA sequence
      dependence of ArgR-DNA binding. The results indicate that subunit assembly plays
      no role in activation, although communication among subunits of the ArgR hexamer
      is required for specific DNA binding. The data suggest that DNA is also an
      allosteric effector of ArgR.

PMID- 11580242
TI  - Promoter suppression in cultured mammalian cells can be blocked by the chicken
      beta-globin chromatin insulator 5'HS4 and matrix/scaffold attachment regions.
AB  - Studies have indicated that two transcriptionally active units can repress one
      another when they lie adjacent in head-to-tail tandem on a chromosome. Repression
      of a downstream (3') unit by an upstream (5') unit is known as "transcriptional
      interference", whereas repression of a 5' unit by a 3' unit is termed "promoter
      suppression". These two processes can occur between head-to-tail tandem copies of
      a transgene, or between transgenes and adjacent chromosomal genes. Interference
      can be blocked by inserting a transcription terminator between adjacent units.
      Here, we report that "promoter suppression" could be blocked by the insulator 5'
      DNaseI hypersensitive site 4, or matrix/scaffold attachment regions (MAR/SARs),
      when these elements were interposed between adjacent units. Because intergenic
      spacers of many repeated eukaryotic genes contain MAR/SARs and insulators, our
      observations suggest that these elements have the ability to segregate repeated
      genes into domains that act independently of one another. Our observations also
      suggest strategies to design transgenes that can act as autonomous units of
      expression.

PMID- 11580243
TI  - The inhibitory effect of the autoantigen La on in vitro 3' processing of
      mammalian precursor tRNAs.
AB  - Mammalian tRNA 3' processing endoribonuclease (3' tRNase) can remove a 3' trailer
      from various precursor (pre)-tRNAs. We investigated what effect the autoantigen
      La has on 3' processing, since the La protein is known to bind to a 3'-terminal
      uridine tract of pre-tRNAs. We tested sixteen different pre-tRNA(Arg) substrates
      containing various 3' trailers with or without a 5' leader sequence for in vitro
      processing by pig 3' tRNase, and for gel-retardation in the presence or absence
      of human La protein. The R-TUUU series consists of four pre-tRNAs containing 6,
      8, 11 and 15 nt 3' trailers ending with UUU and no 5' leader, while the R-TAGC
      series consists of the same four pre-tRNAs as R-TUUU except that the terminal
      sequence is AGC. The R-6LTUUU and R-6LTAGC series are derived from R-TUUU and R
      TAGC, respectively, by adding a 6 nt 5' leader. La differentially inhibited their
      processing and bound to the pre-tRNAs; the 50 % inhibitory concentrations for the
      R-TUUU, R-TAGC, R-6LTUUU, and R-6LTAGC series were 82 to >850, >850, 2 to 292 and
      573 to 785 nM, respectively, and the dissociation constants were 10 to 840, >850,
      3 to 203 and 155 to 520 nM, respectively. These results indicate that both the
      terminal sequence UUU and the 5' leader contribute to more severe inhibition of
      3' processing via tighter interaction with La. With respect to the R-TUUU and R
      6LTUUU series, on the whole, the La inhibition was enhanced as the 3' trailer
      lengths decreased. Taken together, our results suggest that the La protein
      sterically hinders 3' tRNase from binding a pre-tRNA molecule probably near the
      cleavage site.

PMID- 11580244
TI  - HIV-1 nucleocapsid protein zinc finger structures induce tRNA(Lys,3) structural
      changes but are not critical for primer/template annealing.
AB  - Retroviral reverse transcriptases use host cellular tRNAs as primers to initiate
      reverse transcription. In the case of human immunodeficiency virus type 1 (HIV
      1), the 3' 18 nucleotides of human tRNA(Lys,3) are annealed to a complementary
      sequence on the RNA genome known as the primer binding site (PBS). The HIV-1
      nucleocapsid protein (NC) facilitates this annealing. To understand the
      structural changes that are induced upon NC binding to the tRNA alone, we
      employed a chemical probing method using the lanthanide metal terbium. At low
      concentrations of NC, the strong terbium cleavage observed in the core region of
      the tRNA is significantly attenuated. Thus, NC binding first results in
      disruption of the tRNA's metal binding pockets, including those that stabilize
      the D-TPsiC tertiary interaction. When NC concentrations approach the amount
      needed for complete primer/template annealing, NC further destabilizes the tRNA
      acceptor-TPsiC stem minihelix, as evidenced by increased terbium cleavage in this
      domain. A mutant form of NC (SSHS NC), which lacks the zinc finger structures, is
      able to anneal tRNA(Lys,3) efficiently to the PBS, and to destabilize the tRNA
      tertiary core, albeit less effectively than wild-type NC. This mutant form of NC
      does not affect cleavage significantly in the helical regions, even when bound at
      high concentrations. These results, as well as experiments conducted in the
      presence of polyLys, suggest that in the absence of the zinc finger structures,
      NC acts as a polycation, neutralizing the highly negative phosphodiester
      backbone. The presence of an effective multivalent cationic peptide is sufficient
      for efficient tRNA primer annealing to the PBS.

PMID- 11580245
TI  - Comparison of bacteriophage T4 UvsX and human Rad51 filaments suggests that RecA
      like polymers may have evolved independently.
AB  - The UvsX protein from bacteriophage T4 is a member of the RecA/Rad51/RadA family
      of recombinases active in homologous genetic recombination. Like RecA, Rad51 and
      RadA, UvsX forms helical filaments on DNA. We have used electron microscopy and a
      novel method for image analysis of helical filaments to show that UvsX-DNA
      filaments exist in two different conformations: an ADP state and an ATP state. As
      with RecA protein, these two states have a large difference in pitch. Remarkably,
      even though UvsX is only weakly homologous to RecA, both UvsX filament states are
      more similar to the RecA crystal structure than are RecA-DNA filaments. We use
      this similarity to fit the RecA crystal structure into the UvsX filament, and
      show that two of the three previously described blocks of similarity between UvsX
      and RecA are involved in the subunit-subunit interface in both the UvsX filament
      and the RecA crystal filament. Conversely, we show that human Rad51-DNA filaments
      have a different subunit-subunit interface than is present in the RecA crystal,
      and this interface involves two blocks of sequence similarity between Rad51 and
      RecA that do not overlap with those found between UvsX and RecA. This suggests
      that helical filaments in the RecA/Rad51/RadA family may have arisen from
      convergent evolution, with a conserved core structure that has assembled into
      multimeric filaments in a number of different ways.

PMID- 11580246
TI  - Dynamics and cooperativity of microtubule decoration by the motor protein
      kinesin.
AB  - We describe a theoretical and experimental analysis of the interaction between
      microtubules and dimeric motor proteins (kinesin, NCD), with special emphasis on
      the stoichiometry of the interaction, cooperative effects, and their consequences
      for the interpretation of biochemical and image reconstruction results. Monomeric
      motors can bind equivalently to microtubules without interference, at a
      stoichiometry of one motor head per tubulin subunit (alphabeta-heterodimer). By
      contrast, dimeric motors can interact with stoichiometries ranging between one
      and two heads per tubulin subunit, depending on binding constants of the first
      head and the subsequent binding of the second head, and the concentration of
      dimers in solution. Further, we show that an attractive interaction between the
      bound motor molecules can explain the higher periodicities observed in decorated
      microtubules (e.g. 16 nm periodicity), and the non-uniform decoration of a
      population of microtubules and give an estimate of the strength of this
      interaction.

PMID- 11580248
TI  - Intrinsic bending and deformability at the T-A step of CCTTTAAAGG: a comparative
      analysis of T-A and A-T steps within A-tracts.
AB  - Introduction of a T-A or pyrimidine-purine step into a straight and rigid A-tract
      can cause a positive roll deformation that kinks the DNA helix at that step. In
      CCTTTAAAGG, the central T-A step has an 8.6 degrees bend toward the major groove.
      We report the structural analysis of CCTTTAAAGG and a comparison with 25 other
      representative crystal structures from the NDB containing at least four
      consecutive A or T bases. On average, more local bending occurs at the disruptive
      T-A step (8.21 degrees ) than at an A-T step (5.71 degrees ). In addition, A
      tracts containing an A-T step are more bent than are pure A-tracts, and hence A-A
      and A-T steps are not equivalent. All T-A steps examined exhibit positive roll,
      bending towards the major groove, while A-T steps display negative roll and bend
      slightly towards the minor groove. This illustrates how inherent negative and
      positive roll are, respectively, at A-T and T-A steps within A-tracts. T-A steps
      are more deformable, showing larger and more variable deformations of minor
      groove width, rise, cup, twist, and buckle. Standard deviations of twist, rise,
      and cup for T-A steps are 6.66 degrees, 0.55 A, and 15.90 degrees, versus 2.28
      degrees, 0.21 A, and 2.99 degrees for A-T steps. Packing constraints determine
      which local values of these helical parameters an individual T-A step will adopt.
      For instance, with CCTTTAAAGG and three isomorphous structures, CGATTAATCG,
      CGATATATCG, and CGATCGATCG, crystal packing forces lead to a series of correlated
      changes: widened minor groove, large slide, low twist, and large rise. The
      difference in helical parameters between A-T steps lying within A-tracts, versus
      A-T steps within alternating AT sequences, demonstrates the importance of
      neighboring steps on the conformation of a given dinucleotide step.

PMID- 11580247
TI  - Proteolytic analysis of the FliH/FliI complex, the ATPase component of the type
      III flagellar export apparatus of Salmonella.
AB  - The ATPase FliI of the Salmonella type III flagellar protein export apparatus is
      a 456 amino acid residue cytoplasmic protein consisting of two regions, an N
      terminal flagellum-specific region and a C-terminal ATPase region. It forms a
      complex with a regulatory protein FliH in the cytoplasm. Multi-angle light
      scattering studies indicate that FliH forms a homodimer, (FliH)2, and that FliH
      and FliI together form a heterotrimer, (FliH)2FliI. Mobility upon gel-filtration
      chromatography gives much higher apparent molecular masses for both species,
      whereas the mobility of FliI is normal. Sedimentation velocity measurements
      indicate that both (FliH)2 and the FliH/FliI complex are quite elongated. We have
      analyzed FliH, FliI and the FliH/FliI complex for proteolytic sensitivity. FliI
      was degraded by clostripain into two stable fragments, one of 48 kDa (FliI(CL48),
      missing the first seven amino acid residues) and the other of 46 kDa (FliI(CL46),
      missing the first 26 residues). Small amounts of two closely spaced 38 kDa
      fragments (FliI(CL38), missing the first 93 and 97 residues, respectively) were
      also detected. The FliH homodimer was insensitive to clostripain proteolysis and
      provided protection to FliI within the FliH/FliI complex. Neither FliI(CL48) nor
      FliI(CL46) could form a complex with FliH, demonstrating that the N terminus of
      FliI is essential for the interaction. ATP, AMP-PNP, and ADP bound forms of FliI
      within the FliH/FliI complex regained sensitivity to clostripain cleavage. Also,
      the sensitivity of the two FliI(CL38) cleavage sites was much greater in the ATP
      and AMP-PNP bound forms than in either the ADP bound form or nucleotide-free
      FliI. The ATPase domain itself was insensitive to clostripain cleavage. We
      suggest that the N-terminal flagellum-specific region of FliI is flexible and
      changes its conformation during the ATP hydrolysis cycle.

PMID- 11580249
TI  - Crystal structure of rat GTP cyclohydrolase I feedback regulatory protein, GFRP.
AB  - Tetrahydrobiopterin, the cofactor required for hydroxylation of aromatic amino
      acids regulates its own synthesis in mammals through feedback inhibition of GTP
      cyclohydrolase I. This mechanism is mediated by a regulatory subunit called GTP
      cyclohydrolase I feedback regulatory protein (GFRP). The 2.6 A resolution crystal
      structure of rat GFRP shows that the protein forms a pentamer. This indicates a
      model for the interaction of mammalian GTP cyclohydrolase I with its regulator,
      GFRP. Kinetic investigations of human GTP cyclohydrolase I in complex with rat
      and human GFRP showed similar regulatory effects of both GFRP proteins.

PMID- 11580250
TI  - Zooming in on the hydrophobic ridge of H-2D(b): implications for the
      conformational variability of bound peptides.
AB  - Class I major histocompatibility complex (MHC) molecules, which display
      intracellularly processed peptides on the cell surface for scanning by T-cell
      receptors (TCRs), are extraordinarily polymorphic. MHC polymorphism is believed
      to result from natural selection, since individuals heterozygous at the
      corresponding loci can cope with a larger number of pathogens. Here, we present
      the crystal structures of the murine MHC molecule H-2D(b) in complex with the
      peptides gp276 and np396 from the lymphocytic choriomeningitis virus (LCMV),
      solved at 2.18 A and 2.20 A resolution, respectively. The most prominent feature
      of H-2D(b) is a hydrophobic ridge that cuts across its antigen-binding site,
      which is conserved in the L(d)-like family of class I MHC molecules. The
      comparison with previously solved crystal structures of peptide/H-2D(b) complexes
      shows that the hydrophobic ridge focuses the conformational variability of the
      bound peptides in a "hot-spot", which could allow optimal TCR interaction and
      discrimination. This finding suggests a functional reason for the conservation of
      this structural element.

PMID- 11580251
TI  - Dimeric DNA quadruplex containing major groove-aligned A-T-A-T and G-C-G-C
      tetrads stabilized by inter-subunit Watson-Crick A-T and G-C pairs.
AB  - We report on an NMR study of unlabeled and uniformly 13C,15N-labeled d(GAGCAGGT)
      sequence in 1 M NaCl solution, conditions under which it forms a head-to-head
      dimeric quadruplex containing sequentially stacked G-C-G-C, G-G-G-G and A-T-A-T
      tetrads. We have identified, for the first time, a slipped A-T-A-T tetrad
      alignment, involving recognition of Watson-Crick A-T pairs along the major groove
      edges of opposing adenine residues. Strikingly, both Watson-Crick G-C and A-T
      pairings within the direct G-C-G-C and slipped A-T-A-T tetrads, respectively,
      occur between rather than within hairpin subunits of the dimeric d(GAGCAGGT)
      quadruplex. The hairpin turns in the head-to-head dimeric quadruplex involve
      single adenine residues and adds to our knowledge of chain reversal involving
      edgewise loops in DNA quadruplexes. Our structural studies, together with those
      from other laboratories, definitively establish that DNA quadruplex formation is
      not restricted to G(n) repeat sequences, with their characteristic stacked
      uniform G-G-G-G tetrad architectures. Rather, the quadruplex fold is a more
      versatile and robust architecture, accessible to a range of mixed sequences, with
      the potential to facilitate G-C-G-C and A-T-A-T tetrad through major and minor
      groove alignment, in addition to G-G-G-G tetrad formation. The definitive
      experimental identification of such major groove-aligned mixed A-T-A-T and G-C-G
      C tetrads within a quadruplex scaffold, has important implications for the
      potential alignment of duplex segments during homologous recombination.

PMID- 11580252
TI  - Localization of Fe(2+) at an RTGR sequence within a DNA duplex explains
      preferential cleavage by Fe(2+) and H2O2.
AB  - Nicking of duplex DNA by the iron-mediated Fenton reaction occurs preferentially
      at a limited number of sequences. Of these, purine-T-G-purine (RTGR) is of
      particular interest because it is a required element in the upstream regulatory
      regions of many genes involved in iron and oxidative-stress responses. In order
      to study the basis of this preferential nicking, NMR studies were undertaken on
      the RTGR-containing duplex oligonucleotide,
      d(CGCGATATGACACTAG)/d(CTAGTGTCATATCGCG). One-dimensional and two-dimensional 1H
      NMR measurements show that Fe(2+) interacts preferentially and reversibly at the
      ATGA site within the duplex at a rate that is rapid relative to the chemical
      shift timescale, while selective paramagnetic NMR line-broadening of the ATGA
      guanine H8 suggests that Fe(2+) interacts with the guanine N7 moiety.
      Localization at this site is supported by Fe(2+) titrations of a duplex
      containing a 7-deazaguanine substitution in place of the guanine in the ATGA
      sequence. The addition of a 100-fold excess of Mg(2+) over Fe(2+) does not affect
      the Fe(2+)-dependent broadening. When the ATGA site in the duplex is replaced by
      ATGT, an RTGR site (GTGA) is created on the opposite strand. Preferential iron
      localization then takes place at the 3' guanine in GTGA but no longer at the
      guanine in ATGT, consistent with the lack of preferential cleavage of ATGT sites
      relative to ATGA sites.

PMID- 11580253
TI  - Identification and characterization of key kinetic intermediates in amyloid beta
      protein fibrillogenesis.
AB  - Amyloid beta-protein (Abeta) assembly into toxic oligomeric and fibrillar
      structures is a seminal event in Alzheimer's disease, therefore blocking this
      process could have significant therapeutic benefit. A rigorous mechanistic
      understanding of Abeta assembly would facilitate the targeting and design of
      fibrillogenesis inhibitors. Prior studies have shown that Abeta fibrillogenesis
      involves conformational changes leading to the formation of extended beta-sheets
      and that an alpha-helix-containing intermediate may be involved. However, the
      significance of this intermediate has been a matter of debate. We report here
      that the formation of an oligomeric, alpha-helix-containing assembly is a key
      step in Abeta fibrillogenesis. The generality of this phenomenon was supported by
      conformational studies of 18 different Abeta peptides, including wild-type
      Abeta(1-40) and Abeta(1-42), biologically relevant truncated and chemically
      modified Abeta peptides, and Abeta peptides causing familial forms of cerebral
      amyloid angiopathy. Without exception, fibrillogenesis of these peptides involved
      an oligomeric alpha-helix-containing intermediate and the kinetics of formation
      of the intermediate and of fibrils was temporally correlated. The kinetics varied
      depending on amino acid sequence and the extent of peptide N- and C-terminal
      truncation. The pH dependence of helix formation suggested that Asp and His
      exerted significant control over this process and over fibrillogenesis in
      general. Consistent with this idea, Abeta peptides containing Asp-->Asn or His-
      >Gln substitutions showed altered fibrillogenesis kinetics. These data emphasize
      the importance of the dynamic interplay between Abeta monomer conformation and
      oligomerization state in controlling fibrillogenesis kinetics.

PMID- 11580254
TI  - Rough energy landscapes in protein folding: dimeric E. coli Trp repressor folds
      through three parallel channels.
AB  - The folding mechanism of the dimeric Escherichia coli Trp repressor (TR) is a
      kinetically complex process that involves three distinguishable stages of
      development. Following the formation of a partially folded, monomeric ensemble of
      species, within 5 ms, folding to the native dimer is controlled by three kinetic
      phases. The rate-limiting step in each phase is either a non-proline
      isomerization reaction or a dimerization reaction, depending on the final
      denaturant concentration. Two approaches have been employed to test the
      previously proposed folding mechanism of TR through three parallel channels: (1)
      unfolding double-jump experiments demonstrate that all three folding channels
      lead directly to native dimer; and (2) the differential stabilization of the
      transition state for the final step in folding and the native dimer, by the
      addition of salt, shows that all three channels involve isomerization of a
      dimeric species. A refined model for the folding of Trp repressor is presented,
      in which all three channels involve a rapid dimerization reaction between
      partially folded monomers followed by the isomerization of the dimeric
      intermediates to yield native dimer. The ensemble of partially folded monomers
      can be captured at equilibrium by low pH; one-dimensional proton NMR spectra at
      pH 2.5 demonstrate that monomers exist in two distinct, slowly interconverting
      conformations. These data provide a potential structural explanation for the
      three-channel folding mechanism of TR: random association of two different
      monomeric forms, which are distinguished by alternative packing modes of the core
      dimerization domain and the DNA-binding, helix-turn-helix, domain. One, perhaps
      both, of these packing modes contains non-native contacts.

PMID- 11580255
TI  - Folding of horse cytochrome c in the reduced state.
AB  - Equilibrium and kinetic folding studies of horse cytochrome c in the reduced
      state have been carried out under strictly anaerobic conditions at neutral pH, 10
      degrees C, in the entire range of aqueous solubility of guanidinium hydrochloride
      (GdnHCl). Equilibrium unfolding transitions observed by Soret heme absorbance,
      excitation energy transfer from the lone tryptophan residue to the ferrous heme,
      and far-UV circular dichroism (CD) are all biphasic and superimposable, implying
      no accumulation of structural intermediates. The thermodynamic parameters
      obtained by two-state analysis of these transitions yielded DeltaG(H2O)=18.8(+/
      1.45) kcal mol(-1), and C(m)=5.1(+/-0.15) M GdnHCl, indicating unusual stability
      of reduced cytochrome c. These results have been used in conjunction with the
      redox potential of native cytochrome c and the known stability of oxidized
      cytochrome c to estimate a value of -164 mV as the redox potential of the
      unfolded protein. Stopped-flow kinetics of folding and unfolding have been
      recorded by Soret heme absorbance, and tryptophan fluorescence as observables.
      The refolding kinetics are monophasic in the transition region, but become
      biphasic as moderate to strongly native-like conditions are approached. There
      also is a burst folding reaction unobservable in the stopped-flow time window.
      Analyses of the two observable rates and their amplitudes indicate that the
      faster of the two rates corresponds to apparent two-state folding (U<-->N) of 80
      90 % of unfolded molecules with a time constant in the range 190-550 micros
      estimated by linear extrapolation and model calculations. The remaining 10-20 %
      of the population folds to an off-pathway intermediate, I, which is required to
      unfold first to the initial unfolded state, U, in order to refold correctly to
      the native state, N (I<-->U<-->N). The slower of the two observable rates, which
      has a positive slope in the linear functional dependence on the denaturant
      concentration indicating that an unfolding process under native-like conditions
      indeed exists, originates from the unfolding of I to U, which rate-limits the
      overall folding of these 10-20 % of molecules. Both fast and slow rates are
      independent of protein concentration and pH of the refolding milieu, suggesting
      that the off-pathway intermediate is not a protein aggregate or trapped by heme
      misligation. The nature or type of unfolded-state heme ligation does not
      interfere with refolding. Equilibrium pH titration of the unfolded state yielded
      coupled ionization of the two non-native histidine ligands, H26 and H33, with a
      pK(a) value of 5.85. A substantial fraction of the unfolded population persists
      as the six-coordinate form even at low pH, suggesting ligation of the two
      methionine residues, M65 and M80. These results have been used along with the
      known ligand-binding properties of unfolded cytochrome c to propose a model for
      heme ligation dynamics. In contrast to refolding kinetics, the unfolding kinetics
      of reduced cytochrome c recorded by observation of Soret absorbance and
      tryptophan fluorescence are all slow, simple, and single-exponential. In the
      presence of 6.8 M GdnHCl, the unfolding time constant is approximately 300(+/
      125) ms. There is no burst unfolding reaction. Simulations of the observed
      folding-unfolding kinetics by numerical solutions of the rate equations
      corresponding to the three-state I<-->U<-->N scheme have yielded the microscopic
      rate constants.

PMID- 11580256
TI  - The energetics of off-rotamer protein side-chain conformations.
AB  - Non-rotameric ("off-rotamer") conformations are commonly observed for the side
      chains of protein crystal structures. This study examines whether such
      conformations are real or artifactual by comparing the energetics of on and off
      rotamer side-chain conformations calculated with the CHARMM energy function.
      Energy-based predictions of side-chain orientation are carried out by rigid
      geometry mapping in the presence of the fixed protein environment for 1709 non
      polar side-chains in 24 proteins for which high-resolution (2.0 A or better)
      structures are available. For on-rotamer conformations, 97.6 % are correctly
      predicted; i.e. they correspond to the absolute minima of their local side-chain
      energy maps (generally to within 10 degrees or less). By contrast, for the
      observed off-rotamer side-chain conformations, 63.8 % are predicted correctly.
      This difference is statistically significant (P<0.001) and suggests that while
      most of the observed off-rotamer conformations are real, many of the erroneously
      predicted ones are likely to be artifacts of the X-ray refinements. Probabilities
      for off-rotamer conformations of the non-polar side-chains are calculated to be
      5.0-6.1 % by adaptive umbrella-sampled molecular dynamics trajectories of
      individual amino acid residues in vacuum and in the presence of an average
      protein or aqueous dielectric environment. These results correspond closely to
      the 5.7 % off-rotamer fraction predicted by the rigid-geometry mapping studies.
      Since these values are about one-half of the 10.2 % off-rotamer fraction observed
      in the X-ray structures, they support the conclusion that many of the latter are
      artifacts. In both the rigid-geometry mapping and the molecular dynamics studies,
      the discrepancies between the predicted and observed fractions of off-rotamer
      conformations are largest for leucine residues (approximately 6 % versus 16.6 %).
      The simulations for the isolated amino acid residues indicate that the real off
      rotamer frequency of 5-6 % is consistent with the internal side-chain and local
      side-chain-backbone energetics and does not originate from shifts due to the
      protein. The present results suggest that energy-based rotation maps can be used
      to find side-chain positional artifacts that appear in crystal structures based
      on refinements in the 2 A resolution range.

PMID- 11580257
TI  - Chaperonins: folding in the hole.

PMID- 11580258
TI  - Review: mechanisms of disaggregation and refolding of stable protein aggregates
      by molecular chaperones.
AB  - Molecular chaperones are essential for the correct folding of proteins in the
      cell under physiological and stress conditions. Two activities have been
      traditionally attributed to molecular chaperones: (1) preventing aggregation of
      unfolded polypeptides and (2) assisting in the correct refolding of chaperone
      bound denatured polypeptides. We discuss here a novel function of molecular
      chaperones: catalytic solubilization and refolding of stable protein aggregates.
      In Escherichia coli, disaggregation is carried out by a network of ATPase
      chaperones consisting of a DnaK core, assisted by the cochaperones DnaJ, GrpE,
      ClpB, and GroEL-GroES. We suggest a sequential mechanism in which (a) ClpB
      exposes new DnaK-binding sites on the surface of the stable protein aggregates;
      (b) DnaK binds the aggregate surfaces and, by doing so, melts the incorrect
      hydrophobic associations between aggregated polypeptides; (c) ATP hydrolysis and
      DnaK release allow local intramolecular refolding of native domains, leading to a
      gradual weakening of improper intermolecular links; (d) DnaK and GroEL complete
      refolding of solubilized polypeptide chains into native proteins. Thus, active
      disaggregation by the chaperone network can serve as a central cellular tool for
      the recovery of native proteins from stress-induced aggregates and actively
      remove disease-causing toxic aggregates, such as polyglutamine-rich proteins,
      amyloid plaques, and prions.

PMID- 11580259
TI  - Review: a structural view of the GroE chaperone cycle.
AB  - The GroE chaperone system consists of two ring-shaped oligomeric components whose
      association creates different functional states. The most remarkable property of
      the GroE system is the ability to fold proteins under conditions where
      spontaneous folding cannot occur. To achieve this, a fully functional system
      consisting of GroEL, the cochaperone GroES, and ATP is necessary. Driven by ATP
      binding and hydrolysis, this system cycles through different conformational
      stages, which allow binding, folding, and release of substrate proteins. Some
      aspects of the ATP-driven reaction cycle are still under debate. One of these
      open questions is the importance of so-called "football" complexes consisting of
      GroEL and two bound GroES rings. Here, we summarize the evidence for the
      functional relevance of these complexes and their involvement in the efficient
      folding of substrate proteins.

PMID- 11580260
TI  - Review: allostery in chaperonins.
AB  - Chaperonins mediate protein folding in an ATP-dependent manner. ATP binding and
      hydrolysis by chaperonins are subject to both homotropic and heterotropic
      allosteric regulation. In the case of GroEL and CCT, homotropic regulation by ATP
      is manifested in nested cooperativity, which involves positive intra-ring
      cooperativity and negative inter-ring cooperativity in ATP binding. Both types of
      cooperativity are modulated by various heterotropic allosteric effectors, which
      include nonfolded proteins, ADP, Mg2+, monovalent ions such as K+, and
      cochaperonins in the case of type I chaperonins such as GroEL. Here, the
      allosteric properties of chaperonins are reviewed and new results of ours are
      presented with regard to allosteric effects of ADP. The role of allostery in the
      reaction cycle and folding function of chaperonins is discussed.

PMID- 11580261
TI  - Structures of unliganded and ATP-bound states of the Escherichia coli chaperonin
      GroEL by cryoelectron microscopy.
AB  - We have developed an angular refinement procedure incorporating correction for
      the microscope contrast transfer function, to determine cryoelectron microscopy
      (cryo-EM) structures of the Escherichia coli chaperonin GroEL in its apo and ATP
      bound forms. This image reconstruction procedure is verified to 13-A resolution
      by comparison of the cryo-EM structure of unliganded GroEL with the crystal
      structure. Binding, encapsulation, and release of nonnative proteins by GroEL and
      its cochaperone GroES are controlled by the binding and hydrolysis of ATP. Seven
      ATP molecules bind cooperatively to one heptameric ring of GroEL. This binding
      causes long-range conformational changes that determine the orientations of
      remote substrate-binding sites, and it also determines the conformation of
      subunits in the opposite ring of GroEL, in a negatively cooperative mechanism.
      The conformation of GroEL-ATP was determined at approximately 15-A resolution. In
      one ring of GroEL-ATP, the apical (substrate-binding) domains are extremely
      disordered, consistent with the high mobility needed for them to achieve the 60
      degrees elevation and 90 degrees twist of the GroES-bound state. Unexpectedly,
      ATP binding also increases the separation between the two rings, although the
      interring contacts are present in the density map.

PMID- 11580262
TI  - The Chaperones of the archaeon Thermoplasma acidophilum.
AB  - Chaperonesare an essential component of a cell's ability to respond to
      environmental challenges. Chaperones have been studied primarily in bacteria, but
      in recent years it has become apparent that some classes of chaperones either are
      very divergent in bacteria relative to archaea and eukaryotes or are missing
      entirely. In contrast, a high degree of similarity was found between the
      chaperonins of archaea and those of the eukaryotic cytosol, which has led to the
      establishment of archaeal model systems. The archaeon most extensively used for
      such studies is Thermoplasma acidophilum, which thrives at 59 degrees C and pH 2.
      Here we review information on its chaperone complement in light of the recently
      determined genome sequence.

PMID- 11580263
TI  - ATP-induced structural change of the thermosome is temperature-dependent.
AB  - Protein folding by chaperonins is powered by ATP binding and hydrolysis. ATPase
      activity drives the folding machine through a series of conformational
      rearrangements, extensively described for the group I chaperonin GroEL from
      Escherichia coli but still poorly understood for the group II chaperonins. The
      latter--archaeal thermosome and eukaryotic TRiC/CCT--function independently of a
      GroES-like cochaperonin and are proposed to rely on protrusions of their own
      apical domains for opening and closure in an ATP-controlled fashion. Here we use
      small-angle neutron scattering to analyze structural changes of the recombinant
      alpha-only and the native alphabeta-thermosome from Thermoplasma acidophilum upon
      their ATPase cycling in solution. We show that specific high-salt conditions, but
      not the presence of MgATP alone, induce formation of higher order thermosome
      aggregates. The mechanism of the open-closed transition of the thermosome is
      strongly temperature-dependent. ATP binding to the chaperonin appears to be a two
      step process: at lower temperatures an open state of the ATP-thermosome is
      predominant, whereas heating to physiological temperatures induces its switching
      to a closed state. Our data reveal an analogy between the ATPase cycles of the
      two groups of chaperonins and enable us to put forward a model of thermosome
      action.

PMID- 11580264
TI  - Review: nucleotide binding to the thermoplasma thermosome: implications for the
      functional cycle of group II chaperonins.
AB  - Structural information on group II chaperonins became available during recent
      years from electron microscopy and X-ray crystallography. Three conformational
      states have been identified for both archaeal and eukaryotic group II
      chaperonins: an open state, a spherical closed conformation, and an intermediate
      asymmetric bullet-shaped form. However, the functional cycle of group II
      chaperonins appears less well understood, although major principles are conserved
      when compared to group I chaperonins: binding of the substrate polypeptide to the
      apical domains of the open state and MgATP-driven conformational changes that
      result in encapsulation of the substrate where folding can proceed presumably in
      the closed ring of the bullet-shaped form. Binding of the transition state
      analogue MgADP-AlF3-H2O in the crystal structure of the Thermoplasma acidophilum
      thermosome suggests that the closed geometry is the enzymatically active
      conformation that performs ATP hydrolysis. Domain movements observed by electron
      microscopy suggest a coupling of ATP hydrolysis and domain movement similar to
      that in the GroE system. The hydrophilic interior of the closed thermosome
      corresponds to the cis-ring of the asymmetric GroEL-GroES complex implicated in
      protein folding.

PMID- 11580265
TI  - Gene duplication and the evolution of group II chaperonins: implications for
      structure and function.
AB  - Chaperonins are multisubunit protein-folding assemblies. They are composed of two
      distinct structural classes, which also have a characteristic phylogenetic
      distribution. Group I chaperonins (called GroEL/cpn60/hsp60) are present in
      Bacteria and eukaryotic organelles while group II chaperonins are found in
      Archaea (called the thermosome or TF55) and the cytoplasm of eukaryotes (called
      CCT or TriC). Gene duplication has been an important force in the evolution of
      group II chaperonins: Archaea possess one, two, or three homologous chaperonin
      subunit-encoding genes, and eight distinct CCT gene families (paralogs) have been
      described in eukaryotes. Phylogenetic analyses indicate that while the
      duplications in archaeal chaperonin genes have occurred numerous times
      independently in a lineage-specific fashion, the eight different CCT subunits
      found in eukaryotes are the products of duplications that occurred early and very
      likely only once in the evolution of the eukaryotic nuclear genome. Analyses of
      CCT sequences from diverse eukaryotic species reveal that each of the CCT
      subunits possesses a suite of invariant subunit-specific amino acid residues
      ("signatures"). When mapped onto the crystal structure of the archaeal chaperonin
      from Thermoplasma acidophilum, these signatures are located in the apical,
      intermediate, and equatorial domains. Regions that were found to be variable in
      length and/or amino acid sequence were localized primarily to the exterior of the
      molecule and, significantly, to the extreme tip of the apical domain (the
      "helical protrusion"). In light of recent biochemical and electron microscopic
      data describing specific CCT-substrate interactions, our results have
      implications for the evolution of subunit-specific functions in CCT.

PMID- 11580266
TI  - Review: nucleotide-dependent conformational changes of the chaperonin containing
      TCP-1.
AB  - Current biochemical and structural studies on the conformational changes induced
      by the nature of nucleotide bound to the chaperonin containing testis complex
      polypeptide 1 (CCT) are examined to see how consistent the data are. This
      exercise suggests that the biochemical and structural data are in good agreement.
      CCT clearly appears as a folding nano-machine fueled by ATP. A careful comparison
      of the biochemical and structural data, however, highlights a number of points
      that remain to be carefully documented in order to better understand the nature
      of the conformational changes in CCT that yield folded target proteins. Special
      effort should be made to clearly answer the points listed at the end of this
      review in order to obtain the dynamic sequence of events yielding folded proteins
      in the eukaryotic cytoplasm similar to what has been obtained for prokaryotes.

PMID- 11580267
TI  - Review: cellular substrates of the eukaryotic chaperonin TRiC/CCT.
AB  - The TCP-1 ring complex (TRiC; also called CCT, for chaperonin containing TCP-1)
      is a large (approximately 900 kDa) multisubunit complex that mediates protein
      folding in the eukaryotic cytosol. The physiological substrate spectrum of TRiC
      is still poorly defined. Genetic and biochemical data show that it is required
      for the folding of the cytoskeletal proteins actin and tubulin. Recent years have
      witnessed a steady stream of reports that describe other proteins that require
      TRiC for proper folding. Furthermore, analysis of the transit of newly
      synthesized proteins through TRiC in intact cells suggests that the chaperonin
      contributes to the folding of a distinct subset of cellular proteins. Here we
      review the current understanding of a role for TRiC in the folding of newly
      synthesized polypeptides, with a focus on some of the individual proteins that
      require TRiC.

PMID- 11580268
TI  - Mutational screen identifies critical amino acid residues of beta-actin mediating
      interaction between its folding intermediates and eukaryotic cytosolic chaperonin
      CCT.
AB  - The three-dimensional reconstruction of apo-CCT-alpha-actin by cryoelectron
      microscopy shows that actin binds either the CCTbeta-CCTdelta or the CCTepsilon
      CCTdelta subunit pairs of the chaperonin in an open and apparently quasi-native
      conformation. The CCT-binding sites are seen located at the tips of the two arms
      of actin and these same regions of actin have been implicated in CCT binding
      through beta-actin peptide-array screening. Three main CCT binding regions exist:
      actin Sites I, II, and III, which are composed of loops that are surface-exposed
      in native actin. Sixty-eight amino acid residues on beta-actin have been screened
      by mutagenesis for effects on CCT interaction in quantitative in vitro
      translation assays in rabbit reticulocyte lysate. Actin seems to be folding
      cooperatively on chaperonin, since certain mutants discriminate CCT binding from
      processing. Actin Site II, located at the tip of actin subdomain 4, is the major
      determinant for CCT binding. Site II is composed of two anti-parallel extended
      beta-strands, with F200-T203 and D244 contributing substantially to the binding
      site. The substrate recognition chemistry of CCT thus seems different from that
      of Group I chaperonins and probably reflects the fact that it needs to be highly
      specific to enable capture and folding of the actins and tubulins.

PMID- 11580269
TI  - Point mutations in a hinge linking the small and large domains of beta-actin
      result in trapped folding intermediates bound to cytosolic chaperonin CCT.
AB  - The 30-A cryo-EM-derived structure of apo-CCT-alpha-actin shows actin opened up
      across its nucleotide-binding cleft and binding to either of two CCT subunit
      pairs, CCTbeta-CCTdelta or CCTepsilon-CCTdelta, in a similar 1:4 arrangement. The
      two main duplicated domains of native actin are linked twice, topologically, by
      the connecting residues, Q137-S145 and P333-S338, and are tightly held together
      by hydrogen bonding with bound adenine nucleotide. We carried out a mutational
      screen to find residues in actin that might be involved in the huge rotations
      observed in the CCT-bound folding intermediate. When two evolutionarily highly
      conserved glycine residues of beta-actin, G146 and G150, were changed to proline,
      both mutant actin proteins were poorly processed by CCT in in vitro translation
      assays; they become arrested on CCT. A three-dimensional reconstruction of the
      substrate-bound ring of the apo-CCT-beta-actin complex shows that beta-actin
      G150P is not able to bind across the chaperonin cavity to interact with the
      CCTdelta subunit. beta-actin G150P seems tightly packed and apparently bound only
      to the CCTbeta and CCTepsilon subunits, which further indicates that these CCT
      subunits drive the interaction between CCT and actin. Hinge opening seems to be
      critical for actin folding, and we suggest that residues G146 and G150 are
      important components of the hinge around which the rigid subdomains, presumably
      already present in early actin folding intermediates, rotate during CCT-assisted
      folding.

PMID- 11580270
TI  - Analysis of the interaction between the eukaryotic chaperonin CCT and its
      substrates actin and tubulin.
AB  - Two mechanisms have thus far been characterized for the assistance by chaperonins
      of the folding of other proteins. The first and best described is that of the
      prokaryotic chaperonin GroEL, which interacts with a large spectrum of proteins.
      GroEL uses a nonspecific mechanism by which any conformation of practically any
      unfolded polypeptide interacts with it through exposed, hydrophobic residues. ATP
      binding liberates the substrate in the GroEL cavity where it is given a chance to
      fold. A second mechanism has been described for the eukaryotic chaperonin CCT,
      which interacts mainly with the cytoskeletal proteins actin and tubulin.
      Cryoelectron microscopy and biochemical studies have revealed that both of these
      proteins interact with CCT in quasi-native, defined conformations. Here we have
      performed a detailed study of the docking of the actin and tubulin molecules
      extracted from their corresponding CCT:substrate complexes obtained from
      cryoelectron microscopy and image processing to localize certain regions in actin
      and tubulin that are involved in the interaction with CCT. These regions of actin
      and tubulin, which are not present in their prokaryotic counterparts FtsA and
      FtsZ, are involved in the polymerization of the two cytoskeletal proteins. These
      findings suggest coevolution of CCT with actin and tubulin in order to counteract
      the folding problems associated with the generation in these two cytoskeletal
      protein families of new domains involved in their polymerization.

PMID- 11580271
TI  - Review: postchaperonin tubulin folding cofactors and their role in microtubule
      dynamics.
AB  - The microtubule cytoskeleton consists of a highly organized network of
      microtubule polymers bound to their accessory proteins: microtubule-associated
      proteins, molecular motors, and microtubule-organizing proteins. The microtubule
      subunits are heterodimers composed of one alpha-tubulin polypeptide and one beta
      tubulin polypeptide that should undergo a complex folding processing before they
      achieve a quaternary structure that will allow their incorporation into the
      polymer. Due to the extremely high protein concentration that exists at the cell
      cytoplasm, there are alpha- and beta-tubulin interacting proteins that prevent
      the unwanted interaction of these polypeptides with the surrounding protein pool
      during folding, thus allowing microtubule dynamics. Several years ago, the
      development of a nondenaturing electrophoretic technique made it possible to
      identify different tubulin intermediate complexes during tubulin biogenesis in
      vitro. By these means, the cytosolic chaperonin containing TCP-1 (CCT or TriC)
      and prefoldin have been demonstrated to intervene through tubulin and actin
      folding. Various other cofactors also identified along the alpha- and beta
      tubulin postchaperonin folding route are now known to have additional roles in
      tubulin biogenesis such as participating in the synthesis, transport, and storage
      of alpha- and beta-tubulin. The future characterization of the tubulin-binding
      sites to these proteins, and perhaps other still unknown proteins, will help in
      the development of chemicals that could interfere with tubulin folding and thus
      modulating microtubule dynamics. In this paper, current knowledge of the above
      postchaperonin folding cofactors, which are in fact chaperones involved in
      tubulin heterodimer quaternary structure achievement, will be reviewed.

PMID- 11580272
TI  - Reduced outer membrane permeability of Escherichia coli O157:H7: suggested role
      of modified outer membrane porins and theoretical function in resistance to
      antimicrobial agents.
AB  - Outer membrane permeability of Escherichia coli O157:H7 was determined by an in
      vivo kinetic model with the periplasmic enzyme alkaline phosphatase [Martinez et
      al. (1996) Biochemistry 35, 1179-1186]. p-Nitrophenyl phosphate (PNPP) substrate,
      added to intact bacteria, must diffuse through the outer membrane to reach the
      enzyme. At low substrate concentration the bacterium was in the perfectly
      reactive state where all molecules that entered the periplasm were captured and
      converted to product. Transmembrane diffusion was rate limiting, and the
      permeability of the outer membrane was determined from kinetic properties. The
      O157:H7 strain grown at 30 degrees C showed one-sixth the permeability of wild
      type E. coli grown at 30 degrees C. Wild-type bacteria grown at >/=37 degrees C
      show a physiological response with a shift in expression of outer membrane porins
      that lowered permeability to PNPP by approximately 70%. The O157:H7 strain did
      not display this temperature-sensitive shift in permeability even though a change
      in porin expression could be visualized by staining intensity of Omp F and Omp C
      on acrylamide gels. Altered behavior of the O157:H7 membrane was also indicated
      by a several thousand-fold lower response to transformation relative to wild-type
      E. coli. Matrix-assisted laser desorption ionization time of flight mass
      spectrometry and electrospray ionization mass spectrometry confirmed the
      expression of the Omp F and Omp C variants that are unique to E. coli O157:H7.
      This reduced outer membrane permeability can contribute to enhanced resistance of
      O157:H7 to antimicrobial agents.

PMID- 11580273
TI  - The interaction of baccatin III with the taxol binding site of microtubules
      determined by a homogeneous assay with fluorescent taxoid.
AB  - The ubiquitous Taxol binding site of microtubules also binds newly discovered
      ligands. We have designed a homogeneous assay for the high throughput detection
      of Taxol biomimetics, based on the displacement of 7-O-[N-(2,7-difluoro-4'
      fluoresceincarbonyl)-L-alanyl]Taxol from its binding site in diluted solutions of
      preserved microtubules. The state of this reference ligand is measured by
      fluorescence anisotropy in a microplate reader, with varying concentrations of
      nonfluorescent competitors. The binding equilibrium constant of Taxol has a value
      K(b) = 3.7 x 10(7) M(-1). We have found that baccatin III, an analogue of Taxol
      without the C-13 side chain, binds with K(b) = 1.5 x 10(5) M(-1), whereas the
      side chain methyl ester is inactive. This was unexpected from the structure
      activity relationship of taxoids but compatible with models of Taxol docked at
      the microtubule site. Baccatin III binding has been confirmed by displacement of
      [(3)H]Taxol and by direct HPLC measurements of its cosedimentation with
      microtubules, among other methods. Consequently, baccatin III induces microtubule
      bundles and multipolar spindles in PtK2 and U937 cells, and mitotic arrest and
      apoptotic death of the U937 cells, at concentrations 200-500-fold larger than
      Taxol. The simplest analysis of these results strongly suggests that the
      interaction of the C-2 C-4 substituted taxane ring system with the microtubule
      binding site provides most (ca. 75%) of the free energy change of Taxol binding
      and is sufficient to activate microtubule stabilization and transmit the
      antitumor effects of Taxol, whereas the C-13 side chain provides a weak specific
      anchor.

PMID- 11580274
TI  - Thiol/disulfide interconversion in bovine lens aldose reductase induced by
      intermediates of glutathione turnover.
AB  - The effectiveness of cysteine and cysteinylglycine to act as protein thiolating
      agents was investigated using bovine lens aldose reductase (ALR2) as the protein
      target. Disulfides of both thiol compounds appear to be very effective as ALR2
      thiolating agents. Cysteine- and CysGly-modified ALR2 forms (Cys-ALR2 and CysGly
      ALR2, respectively) are characterized by the presence of a mixed disulfide bond
      involving Cys298, as demonstrated by a combined electrospray mass spectrometry
      and Edman degradation approach. Both Cys-ALR2 and CysGly-ALR2 essentially retain
      the ability to reduce glyceraldehyde but lose the susceptibility to inhibition by
      Sorbinil and other ALR2 inhibitors. Cys-ALR2 and CysGly-ALR2 are easily reduced
      back to the native enzyme form by dithiothreitol and GSH treatment; on the
      contrary, Cys and 2-mercaptoethanol appear to act as protein trans-thiolating
      agents, rather than reducing agents. The treatment at 37 degrees C of both Cys
      ALR2 and CysGly-ALR2, unlikely what observed for glutathionyl-modified ALR2 (GS
      ALR2), promotes the generation of an intramolecular disulfide bond between Cys298
      and Cys303 residues. A rationale for the special susceptibility of Cys-ALR2 and
      CysGly-ALR2, as compared to GS-ALR2, to the thermally induced intramolecular
      rearrangement is given on the basis of a molecular dynamic and energy
      minimization approach. A pathway of thiol/disulfide interconversion for bovine
      lens ALR2 induced, in oxidative conditions, by physiological thiol compounds is
      proposed.

PMID- 11580275
TI  - Solution structures of the antifungal heliomicin and a selected variant with both
      antibacterial and antifungal activities.
AB  - In response to an experimental infection, the lepidopteran Heliothis virescens
      produces an antifungal protein named heliomicin. Heliomicin displays sequence
      similarities with antifungal plant defensins and antibacterial or antifungal
      insect defensins. To gain information about the structural elements required for
      either antifungal or antibacterial activity, heliomicin and selected point
      mutated variants were expressed in yeast as fusion proteins. The effects of
      mutations, defined by comparing the primary structure of heliomicin with the
      sequences of members of the insect defensin family, were analyzed using
      antibacterial and antifungal assays. One of the variants shows significant
      activity against Gram-positive bacteria while remaining efficient against fungi.
      The three-dimensional structures of this variant and of the wild-type protein
      were determined by two-dimensional (1)H NMR to establish a correlation between
      structure and antibacterial or antifungal activity. Wild-type and mutated
      heliomicins adopt a similar scaffold, including the so-called cysteine-stabilized
      alphabeta motif. A comparison of their structures with other defensin-type
      molecules indicates that common hydrophobic characteristics can be assigned to
      all the antifungal proteins. A comparative analysis of various structural
      features of heliomicin mutant and of antibacterial defensins enables common
      properties to be assessed, which will help to design new mutants with increased
      antibacterial activity.

PMID- 11580276
TI  - Backbone dynamics for the wild type and a double H52R/T56W mutant of the vnd/NK-2
      homeodomain from Drosophila melanogaster.
AB  - The (15)N relaxation behavior and heteronuclear Overhauser effect data for the
      wild type and an H52R/T56W double mutant protein that encompasses the vnd/NK-2
      homeodomain from Drosophila melanogaster were used to characterize and describe
      the protein backbone dynamics. This investigation, which includes a description
      of a model structure for the H52R/T56W double mutant vnd/NK-2 homeodomain, was
      carried out for the two proteins in both the free and DNA-bound states. The
      double residue replacement at positions 52 and 56 within the DNA recognition
      helix of vnd/NK-2 has been shown to lead to a significant secondary structural
      modification resulting in an increase in the length of the recognition helix for
      the unbound protein. These structural changes are accompanied by corresponding
      changes in the T(1) and T(1)(rho) relaxation times as well as in the
      heteronuclear Overhauser effect (XNOE) values that show that the structural
      stability of the protein is enhanced by the two residue replacements. The values
      of the rotational anisotropy, D(parallel)/D(perpendicular), derived from analysis
      of the (15)N T(1) and T(1)(rho) relaxation values are small (1.189 for the
      unbound homeodomain and 1.110 for the bound homeodomain; both analyzed as prolate
      ellipsoids of revolution). A comparison of the T(2) values of the wild type and
      double mutant homeodomain reveals the presence of a low-frequency exchange
      contribution for the wild type analogue. These relaxation studies show that the
      motional behavior of the protein primarily reflects the tertiary structure and
      stability of the homeodomain backbone as well as the respective changes induced
      upon site-directed residue replacement or DNA binding.

PMID- 11580277
TI  - Crystal structure of the Msx-1 homeodomain/DNA complex.
AB  - The Msx-1 homeodomain protein plays a crucial role in craniofacial, limb, and
      nervous system development. Homeodomain DNA-binding domains are comprised of 60
      amino acids that show a high degree of evolutionary conservation. We have
      determined the structure of the Msx-1 homeodomain complexed to DNA at 2.2 A
      resolution. The structure has an unusually well-ordered N-terminal arm with a
      unique trajectory across the minor groove of the DNA. DNA specificity conferred
      by bases flanking the core TAAT sequence is explained by well ordered water
      mediated interactions at Q50. Most interactions seen at the TAAT sequence are
      typical of the interactions seen in other homeodomain structures. Comparison of
      the Msx-1-HD structure to all other high resolution HD-DNA complex structures
      indicate a remarkably well-conserved sphere of hydration between the DNA and
      protein in these complexes.

PMID- 11580278
TI  - Mechanistic characterization of the HDV genomic ribozyme: assessing the catalytic
      and structural contributions of divalent metal ions within a multichannel
      reaction mechanism.
AB  - Hepatitis delta virus (HDV) uses genomic and antigenomic ribozymes in its
      replication cycle. We examined ribozyme self-cleavage over eight orders of
      magnitude of Mg(2+) concentration, from approximately 10(-9) to 10(-1) M. These
      experiments were carried out in 1 M NaCl to aid folding of the ribozyme and to
      control the ionic strength. The concentration of free Mg(2+) ions was established
      using an EDTA-Mg(2+) buffered system. Over the pH range of 5-9, the rate was
      independent of Mg(2+) concentration up to 10(-7) M, and of the addition of a
      large excess of EDTA. This suggests that in the presence of 1 M NaCl, the
      ribozyme can fold and cleave without using divalent metal ions. Bronsted analysis
      under these reaction conditions suggests that solvent and hydroxide ions may play
      important roles as general base and specific base catalysts. The observed rate
      constant displayed a log-linear dependence on intermediate Mg(2+) concentration
      from approximately 10(-7) to 10(-4) M. These data combined with the shape of the
      pH profile under these conditions are consistent with the binding of at least one
      structural divalent metal ion that does not participate in catalysis and binds
      tighter at lower pH. No evidence for a catalytic role for Mg(2+) was found at low
      or intermediate Mg(2+) concentrations. Addition of Mg(2+) to physiological and
      higher concentrations, from 10(-3) to 10(-1) M, revealed a second saturable
      divalent metal ion which binds tighter at high pH. The shape of the pH profile is
      inverted relative to that at low Mg(2+) concentrations, consistent with a general
      acid-base catalysis mechanism in which a cytosine (C75) acts as the general acid
      and a hydroxide ion from the divalent metal ion, or possibly from solvent, acts
      as the base. Overall, the data support a model in which the HDV ribozyme can self
      cleave by multiple divalent ion-independent and -dependent channels, and in which
      the contribution of Mg(2+) to catalysis is modest at approximately 25-fold.
      Surface electrostatic potential maps were calculated on the self-cleaved form of
      the ribozyme using the nonlinear Poisson-Boltzmann equation. These calculations
      revealed several patches of high negative potential, one of which is present in a
      cleft near N4 of C75. These calculations suggest that distinct catalytic and
      structural metal ion sites exist on the ribozyme, and that the negative potential
      at the active site may help shift the pK(a) for N3 of C75 toward neutrality.

PMID- 11580279
TI  - Constitutive activation of the mu opioid receptor by mutation of D3.49(164), but
      not D3.32(147): D3.49(164) is critical for stabilization of the inactive form of
      the receptor and for its expression.
AB  - The roles of conserved aspartates in the third transmembrane domain of the rat mu
      opioid receptor (RMOR) were explored with mutations of D3.32(147) and D3.49(164).
      D3.49(164) in the highly conserved DRY motif was mutated to 13 amino acids.
      Except for the D3.49(164)E mutant, each mutant displayed little or no detectable
      [(3)H]diprenorphine binding, and pretreatment with naloxone greatly enhanced
      binding. D3.49(164)H, -Q, -Y, -M, and -E mutants were further studied. D3.32(147)
      was substituted with A or N. All seven mutants exhibited similar binding
      affinities for the antagonist [(3)H]diprenorphine as the wild-type. The
      D3.49(164)H, -Q, -Y, and -M mutants, but not the D3.49(164)E and D3.32(147)
      mutants, exhibited enhanced basal [(35)S]GTPgammaS binding which was comparable
      to the maximally activated level of the wild-type and was related to expression
      levels. Naloxone, naltrexone, and naloxone methiodide significantly inhibited the
      basal [(35)S]GTPgammaS binding of the D3.49(164) mutants, indicating inverse
      agonist activities. Treatment of the D3.49(164)Y mutant with pertussis toxin
      greatly reduced the basal [(35)S]GTPgammaS binding, demonstrating constitutive
      activation of Galpha(i)/Galpha(o). The D3.49(164)H, -Y, -M, and -Q mutants had
      higher affinities for DAMGO than the wild-type, which were not significantly
      lowered by GTPgammaS. Thus, mutation of D3.49(164) to H, Y, M, or Q in RMOR
      resulted in receptor assuming activated conformations. In contrast, the
      D3.49(164)E mutant displayed significantly lower basal [(35)S]GTPgammaS binding
      and reduced affinity for DAMGO. Upon incubation of membranes at 37 degrees C, the
      constitutively active D3.49(164)Y mutant was structurally less stable, whereas
      the inactivated D3.49(164)E mutant was more stable, than the wild-type.
      Computational simulations showed that the E3.49 side chain interacted strongly
      with the conserved R3.50 in the DRY motif and stabilized the inactive form of the
      receptor. Taken together, these results indicate that D3.49 plays an important
      role in constraining the receptor in inactive conformations.

PMID- 11580280
TI  - Kinetic analysis of product inhibition in human manganese superoxide dismutase.
AB  - Manganese superoxide dismutase (MnSOD) cycles between the Mn(II) and Mn(III)
      states during the catalyzed disproportionation of O(2)(*-), a catalysis that is
      limited at micromolar levels of superoxide by a peroxide-inhibited complex with
      the metal. We have investigated the role in catalysis and inhibition of the
      conserved residue Trp161 which forms a hydrophobic side of the active site cavity
      of MnSOD. Crystal structures of mutants of human MnSOD in which Trp161 was
      replaced with Ala or Phe showed significant conformational changes on adjacent
      residues near the active site, particularly Gln143 and Tyr34 which in wild-type
      MnSOD participate in a hydrogen bond network believed to support proton transfer
      during catalysis. Using pulse radiolysis and observing the UV absorbance of
      superoxide, we have determined rate constants for the catalytic dismutation of
      superoxide. In addition, the rates of formation and dissociation of the product
      inhibited complex of these mutants were determined by direct observation of the
      characteristic visible absorption of the oxidized and inhibited states. Catalysis
      by W161A and W161F MnSOD was associated with a decrease of at least 100-fold in
      the catalytic rate of reduction of superoxide, which then promotes a competing
      pathway leading to product inhibition. The structural changes caused by the
      mutations at position 161 led to small changes, at most a 6-fold decrease, in the
      rate constant for formation of the inhibited complex. Solvent hydrogen isotope
      effects support a mechanism in which formation of this complex, presumably the
      peroxide dianion bound to the manganese, involves no rate-contributing proton
      transfer; however, the dissociation of the complex requires proton transfer to
      generate HO(2)(-) or H2O2.

PMID- 11580281
TI  - Enhanced binding of a rationally designed peptide ligand of concanavalin a arises
      from improved geometrical complementarity.
AB  - The structural basis of affinity enhancement was addressed by analyzing the
      interactions between concanavalin A and the carbohydrate-mimicking peptide
      ligands. Based on the crystal structures of concanavalin A in complex with these
      peptides [Jain, D., Kaur, K. J., Sundaravadivel, B., and Salunke, D. M. (2000) J.
      Biol. Chem. 275, 16098-16102; Jain, D., Kaur, K. J., and Salunke, D. M. (2001)
      Biophys. J. 80, 2912-2921], a high-affinity analogue was designed. This analogue
      (acetyl-MYWYPY-amide) binds to the lectin with 32-fold enhanced affinity compared
      to the corresponding precursor peptides. The crystal structure of concanavalin A
      bound to the designed peptide has been determined. A peptide molecule binds to
      each of the crystallographically independent monomers of the tetrameric lectin.
      The four bound peptide molecules exhibit two major conformations both of which
      are extended. Unlike in the case of other concanavalin A binding peptides, the
      structural variations within different conformers of this analogue are marginal.
      It is apparent that the deletion of the structurally variable region of the
      larger peptides has led to an improved complementarity and increased buried
      surface area in the case of the designed peptide. The crystal structure also
      showed the formation of two backbone hydrogen bonds between the ligand and the
      ligate which were not present in the complexes of the precursor peptides. The
      observed structural features adequately explain the enhanced binding of the
      designed analogue.

PMID- 11580282
TI  - A novel calcium-regulated membrane guanylate cyclase transduction system in the
      olfactory neuroepithelium.
AB  - This report defines the identity of a calcium-regulated membrane guanylate
      cyclase transduction system in the cilia of olfactory sensory neurons, which is
      the site of odorant transduction. The membrane fraction of the neuroepithelial
      layer of the rat exhibited Ca(2+)-dependent guanylate cyclase activity, which was
      eliminated by the addition of EGTA. This indicated that the cyclase did not
      represent a rod outer segment guanylate cyclase (ROS-GC), which is inhibited by
      free Ca(2+). This interpretation was supported by studies with the Ca(2+) binding
      proteins, GCAPs (guanylate cyclase activating proteins), which stimulate
      photoreceptor ROS-GC in the absence of Ca(2+). They did not stimulate the
      olfactory neuroepithelial membrane guanylate cyclase. The olfactory
      neuroepithelium contained a Ca(2+) binding protein, neurocalcin, which stimulated
      the cyclase in a Ca(2+)-dependent fashion. The cyclase was cloned from the
      neuroepithelium and was found to be identical in structure to that of the
      previously cloned cyclase termed GC-D. The cyclase was expressed in a
      heterologous cell system, and was reconstituted with its Ca(2+)-dependent
      activity in the presence of recombinant neurocalcin. The reconstituted cyclase
      mimicked the native enzyme. Immunocytochemical studies showed that the guanylate
      cyclase coexists with neurocalcin in the apical region of the cilia. Deletion
      analysis showed that the neurocalcin-regulated domain resides at the C-terminal
      region of the cyclase. The findings establish the biochemical, molecular, and
      functional identity of a novel Ca(2+)-dependent membrane guanylate cyclase
      transduction system in the cilia of the olfactory epithelium, suggesting a
      mechanism of the olfactory neuroepithelial guanylate cyclase regulation
      fundamentally distinct from the phototransduction-linked ROS-GC.

PMID- 11580283
TI  - Structural characterization of beta-cardiac myosin subfragment 1 in solution.
AB  - beta-cardiac myosin subfragment 1 (betaS1) tertiary structure and dynamics were
      characterized with proteolytic digestion, nucleotide analogue trapping kinetics,
      and intrinsic fluorescence changes accompanying nucleotide binding. Proteolysis
      of betaS1 produces the 25, 50, and 20 kDa fragments and a new cut within the 50
      kDa fragment at Arg369. F-actin inhibits cleavage of the 50-kDa fragment and
      fails to inhibit cleavage at the 50/20 kDa junction, suggesting betaS1 presents
      an actoS1 conformation fundamentally different from skeletal S1. Time-dependent
      changes in Mg(2+)-ATPase accompanying proteolysis identifies cleavage points that
      lie within the energy transduction pathway. The nucleotide analogue trapping
      kinetics reveal the presence of a reversible weakly actin attached state.
      Comparison of nucleotide analogue induced betaS1 structures with the transient
      structures occurring during ATPase indicates analogue induced and transient
      structures are in a one-to-one correspondence. Tryptophan fluorescence
      enhancement accompanies the binding or trapping of nucleotide or nucleotide
      analogues. Isolation of Trp508 fluorescence shows it is an ATP-sensitive
      tryptophan and that its vicinity changes conformation sequentially with the
      transient intermediates accompanying ATPase. These studies elucidate energy
      transduction and suggest how mutations of betaS1 implicated in disease might
      undermine function, stability, or efficiency.

PMID- 11580284
TI  - There is communication between all four Ca(2+)-bindings sites of calcineurin B.
AB  - We have used site-directed mutagenesis, flow dialysis, and Fourier transform
      infrared (FTIR) spectroscopy to study Ca(2+)-binding to the regulatory component
      of calcineurin. Single Glu-Gln(E --> Q) mutations were used to inactivate each of
      the four Ca(2+)-binding sites of CnB in turn, generating mutants Q1, Q2, Q3, and
      Q4, with the number indicating which Ca(2+) site is inactivated. The binding data
      derived from flow dialysis reveal two pairs of sites in the wild-type protein,
      one pair with very high affinity and the other with lower affinity Ca(2+)-binding
      sites. Also, only three sites are titratable in the wild-type protein because one
      site cannot be decalcified. Mutation of site 2 leaves the protein with only two
      titratable sites, while mutation of sites 1, 3, or 4 leave three titratable sites
      that are mostly filled with 3 Ca(2+) equiv added. The binding data further show
      that each of the single-site mutations Q2, Q3, and Q4 affects the affinities of
      at least one of the remaining sites. Mutation in either of sites 3 or 4 results
      in a protein with no high-affinity sites, indicating communication between the
      two high-affinity sites, most likely sites 3 and 4. Mutation in site 2 decreases
      the affinity of all three remaining sites, though still leaving two relatively
      high-affinity sites. The FTIR data support the conclusions from the binding data
      with respect to the number of titratable sites as well as the impact of each
      mutation on the affinities of the remaining sites. We conclude therefore that
      there is communication between all four Ca(2+)-binding sites. In addition, the
      Ca(2+) induced changes in the FTIR spectra for the wild-type and Q4 mutant are
      most similar, suggesting that the same three Ca(2+)-binding sites are being
      titrated, i.e., site 4 is the very high-affinity site under the conditions of the
      FTIR experiments.

PMID- 11580285
TI  - A polyalanine-based peptide cannot form a stable transmembrane alpha-helix in
      fully hydrated phospholipid bilayers.
AB  - The conformation and amide proton exchangeability of the peptide acetyl-K(2)
      A(24)-K(2)-amide (A(24)) and its interaction with phosphatidylcholine bilayers
      were examined by a variety of physical techniques. When dissolved in or cast from
      methanol as a dried film, A(24) is predominantly alpha-helical. In aqueous media,
      however, A(24) exists primarily as a mixture of helical (though not necessarily
      alpha-helical) and random coiled structures, both of which allow rapid H-D
      exchange of all amide protons. When incorporated into phospholipids in the
      absence of water, A(24) also exists primarily as a transmembrane alpha-helix.
      However, upon hydration of that system, rapid exchange of all amide protons also
      occurs along with a marked change in the amide I absorption band of the peptide.
      Also, when dispersed with phosphatidylcholine in aqueous media, the conformation
      and thermal stability of A(24) are not significantly altered by the presence of
      the phospholipid or by its gel/liquid-crystalline phase transition. Differential
      scanning calorimetric and electron spin resonance spectroscopic studies indicate
      that A(24) has relatively minor effects on the thermodynamic properties of the
      lipid hydrocarbon chain-melting phase transition, that it does not abolish the
      lipid pretransition, and that its presence has no significant effect on the
      orientational order or rates of motion of the phospholipid hydrocarbon chains. We
      therefore conclude that A(24) has sufficient alpha-helical propensity, but
      insufficient hydrophobicity, to maintain a stable transmembrane association with
      phospholipid bilayers in the presence of water. Instead, it exists primarily as a
      dynamic mixture of helices and other conformers and resides mostly in the aqueous
      phase where it interacts weakly with the bilayer surface or with the polar/apolar
      interfacial region of phosphatidylcholine bilayers. Thus, polyalanine-based
      peptides are not good models for the transmembrane alpha-helical segments of
      natural membrane proteins.

PMID- 11580286
TI  - Ticlopidine as a selective mechanism-based inhibitor of human cytochrome P450
      2C19.
AB  - Experiments using recombinant yeast-expressed human liver cytochromes P450
      confirmed previous literature data indicating that ticlopidine is an inhibitor of
      CYP 2C19. The present studies demonstrated that ticlopidine is selective for CYP
      2C19 within the CYP 2C subfamily. UV-visible studies on the interaction of a
      series of ticlopidine derivatives with CYP 2C19 showed that ticlopidine binds to
      the CYP 2C19 active site with a K(s) value of 2.8 +/- 1 microM. Derivatives that
      do not involve either the o-chlorophenyl substituent, the free tertiary amine
      function, or the thiophene ring of ticlopidine did not lead to such spectral
      interactions and failed to inhibit CYP 2C19. Ticlopidine is oxidized by CYP 2C19
      with formation of two major metabolites, the keto tautomer of 2
      hydroxyticlopidine (1) and the dimers of ticlopidine S-oxide (TSOD) (V(max) = 13
      +/- 2 and 0.4 +/- 0.1 min(-1)). During this oxidation, CYP 2C19 was inactivated;
      the rate of its inactivation was time and ticlopidine concentration dependent.
      This process meets the chemical and kinetic criteria generally accepted for
      mechanism-based enzyme inactivation. It occurs in parralel with CYP 2C19
      catalyzed oxidation of ticlopidine, is inhibited by an alternative well-known
      substrate of CYP 2C19, omeprazole, and correlates with the covalent binding of
      ticlopidine metabolite(s) to proteins. Moreover, CYP 2C19 inactivation is not
      inhibited by the presence of 5 mM glutathione, suggesting that it is due to an
      alkylation occurring inside the CYP 2C19 active site. The effects of ticlopidine
      on CYP 2C19 are very analogous with those previously described for the
      inactivation of CYP 2C9 by tienilic acid. This suggests that a similar
      electrophilic intermediate, possibly a thiophene S-oxide, is involved in the
      inactivation of CYP 2C19 and CYP 2C9 by ticlopidine and tienilic acid,
      respectively. The kinetic parameters calculated for ticlopidine-dependent
      inactivation of CYP 2C19, i.e., t(1/2max) = 3.4 min, k(inact) = 3.2 10(-3) s(-1),
      K(I) = 87 microM, k(inact)/K(I) = 37 L.mol(-1).s(-1), and r (partition ratio) =
      26 (in relation with formation of 1 + TSOD), classify ticlopidine as an efficient
      mechanism-based inhibitor although somewhat less efficient than tienilic acid for
      CYP 2C9. Importantly, ticlopidine is the first selective mechanism-based
      inhibitor of human liver CYP 2C19 and should be a new interesting tool for
      studying the topology of the active site of CYP 2C19.

PMID- 11580287
TI  - Expression, purification, characterization, and NMR studies of highly deuterated
      recombinant cytochrome c peroxidase.
AB  - Two forms of extensively deuterated S. cerevisiae cytochrome c peroxidase (CcP;
      EC 1.11.1.5) have been overexpressed in E. coli by growth in highly deuterated
      medium. One of these ferriheme enzyme forms (recDCcP) was produced using >97%
      deuterated growth medium and was determined to be approximately 84% deuterated.
      The second form [recD(His)CcP] was grown in the same highly deuterated medium
      that had been supplemented with excess histidine (at natural hydrogen isotope
      abundance) and was also approximately 84% deuterated. This resulted in direct
      histidine incorporation without isotope scrambling. Both of these enzymes along
      with the corresponding recombinant native CcP (recNATCcP), which was expressed in
      a standard medium with normal hydrogen isotope abundance, consisted of 294 amino
      acid polypeptide chains having the identical sequence to the yeast-isolated
      enzyme, without any N-terminal modifications. Comparative characterizations of
      all three enzymes have been carried out for the resting-state, high-spin forms
      and in the cyanide-ligated, low-spin forms. The primary physical methods employed
      were electrophoresis, UV-visible spectroscopy, hydrogen peroxide reaction
      kinetics, mass spectrometry, and (1)H NMR spectroscopy. The results indicate that
      high-level deuteration does not significantly alter CcP's reactivity or
      spectroscopy. As an example of potential NMR uses, recDCcPCN and recD(His)CcPCN
      have been used to achieve complete, unambiguous, stereospecific (1)H resonance
      assignments for the heme hyperfine-shifted protons, which also allows the heme
      side chain conformations to be assessed. Assigning these important active-site
      protons has been an elusive goal since the first NMR spectra on this enzyme were
      reported 18 years ago, due to a combination of the enzyme's comparatively large
      size, paramagnetism, and limited thermal stability.

PMID- 11580288
TI  - Manipulating the direction of electron transfer in the bacterial reaction center
      by swapping Phe for Tyr near BChl(M) (L181) and Tyr for Phe near BChl(L) (M208).
AB  - We have investigated the primary charge separation processes in Rb. capsulatus
      reaction centers (RCs) bearing the mutations Phe(L181) --> Tyr, Tyr(M208) -->
      Phe, and Leu(M212) --> His. In the YFH mutant, decay of the excited primary
      electron donor P occurs with an 11 +/- 2 ps time constant and is trifurcated to
      give (1) internal conversion to the ground state ( approximately 10% yield), (2)
      charge separation to the L side of the RC ( approximately 60% yield), and (3)
      electron transfer to the M-side bacteriopheophytin BPh(M) ( approximately 30%
      yield). These results relate previous work in which the ionizable residues Lys
      (at L178) and Asp (at M201) have been used to facilitate charge separation to the
      M side of the RC, and the widely studied L181 and M208 mutants. One conclusion
      that comes from this work is that the Tyr (M208) --> Phe and Gly(M201) --> Asp
      mutations near the L-side bacteriochlorophyll (BChl(L)) raise the free energy of
      P(+)BChl(L)(-) by comparable amounts. The results also suggest that the free
      energy of P(+)BChl(M)(-) is lowered more substantially by a Tyr at L181 than a
      Lys at L178. The results on the YFH mutant further demonstrate that the free
      energy differences between the L- and M-side charge-separated states play a
      significant role in the directionality of charge separation in the wild-type RC,
      and place limits on the contributing role of differential electronic matrix
      elements on the two sides of the RC.

PMID- 11580289
TI  - Molecular mechanism of sequence-specific termination of lentiviral replication.
AB  - The central termination sequence (CTS) terminates (+) strand DNA synthesis in
      certain lentiviruses. The molecular mechanism underlying this event, catalyzed by
      equine infectious anemia virus reverse transcriptase (EIAV RT), was evaluated by
      pre-steady-state kinetic techniques. Time courses in nucleotide incorporation
      using several DNA substrates were biphasic, consistent with release of enzyme
      from extended DNA being the rate-limiting step for turnover. While the burst
      amplitude reflecting the amount of functional RT-DNA complex was sequence
      dependent, rate constants for initial product formation were not. Filter binding
      assays indicate the K(d) for CTS-containing substrate is only 2-fold higher than
      a random DNA and cannot account entirely for the large diminution in burst
      amplitudes. Measurements of processive DNA replication on a millisecond time
      scale indicate that the rate of polymerization is unaffected by the T(6)-tract
      within the CTS. However, termination products accumulate due to a substantial
      increase in the rate of nonproductive enzyme-nucleic acid complex formation after
      incorporation of four to five adenosines of a T(6)-tract within the CTS. During
      strand displacement synthesis through the CTS, products accumulate after
      incorporation of three to four adenosines. The rate of polymerization during
      strand displacement synthesis decreases 2-fold while the rate of nonproductive
      enzyme-nucleic acid complex formation is identical in the absence or presence of
      the displacement strand. These results have allowed us to develop a model for CTS
      induced termination of (+) strand synthesis.

PMID- 11580290
TI  - Substrate specificity and excision kinetics of Escherichia coli endonuclease VIII
      (Nei) for modified bases in DNA damaged by free radicals.
AB  - Endonuclease VIII (Nei) is one of three enzymes in Escherichia coli that are
      involved in base-excision repair of oxidative damage to DNA. We investigated the
      substrate specificity and excision kinetics of this DNA glycosylase for bases in
      DNA that have been damaged by free radicals. Two different DNA substrates were
      prepared by gamma-irradiation of DNA solutions under N(2)O or air, such that they
      contained a multiplicity of modified bases. Although previous studies on the
      substrate specificity of Nei had demonstrated activity on several pyrimidine
      derivatives, this present study demonstrates excision of additional pyrimidine
      derivatives and a purine-derived lesion, 4,6-diamino-5-formamidopyrimidine, from
      DNA containing multiple modified bases. Excision was dependent on enzyme
      concentration, incubation time, and substrate concentration, and followed
      Michaelis-Menten kinetics. The kinetic parameters also depended on the identity
      of the individual modified base being removed. Substrates and excision kinetics
      of Nei and a naturally arising mutant form involving Leu-90-->Ser (L90S-Nei) were
      compared to those of Escherichia coli endonuclease III (Nth), which had
      previously been determined under experimental conditions similar to those in this
      study. This comparison showed that Nei and Nth significantly differ from each
      other in terms of excision rates, although they have common substrates. The
      present work extends the substrate specificity of Nei and shows the effect of a
      single mutation in the nei gene on the specificity of Nei.

PMID- 11580291
TI  - Peptide-derived antagonists of the urokinase receptor. affinity maturation by
      combinatorial chemistry, identification of functional epitopes, and inhibitory
      effect on cancer cell intravasation.
AB  - The high-affinity interaction between urokinase-type plasminogen activator (uPA)
      and its glycolipid-anchored receptor (uPAR) plays an important role in
      pericellular plasminogen activation. Since proteolytic degradation of the
      extracellular matrix has an established role in tumor invasion and metastasis,
      the uPA-uPAR interaction represents a potential target for therapeutic
      intervention. By affinity maturation using combinatorial chemistry we have now
      developed and characterized a 9-mer, linear peptide antagonist of the uPA-uPAR
      interaction demonstrating specific, high-affinity binding to human uPAR (K(d)
      approximately 0.4 nM). Studies by surface plasmon resonance reveal that the off
      rate for this receptor-peptide complex is comparable to that measured for the
      natural protein ligand, uPA. The functional epitope on human uPAR for this
      antagonist has been delineated by site-directed mutagenesis, and its assignment
      to loop 3 of uPAR domain III (Met(246), His(249), His(251), and Phe(256))
      corroborates data previously obtained by photoaffinity labeling and provides a
      molecular explanation for the extreme selectivity observed for the antagonist
      toward human compared to mouse, monkey, and hamster uPAR. When human HEp-3 cancer
      cells were inoculated in the presence of this peptide antagonist, a specific
      inhibition of cancer cell intravasation was observed in a chicken chorioallantoic
      membrane assay. These data imply that design of small organic molecules mimicking
      the binding determinants of this 9-mer peptide antagonist may have a potential
      application in combination therapy for certain types of cancer.

PMID- 11580292
TI  - Probing the importance of the amino-terminal sequence of the beta- and gamma
      chains to the properties of normal adult and fetal hemoglobins.
AB  - A recombinant mutant of human fetal hemoglobin (Hb F), named rHb Oscar, has been
      constructed to explore the importance of the sequence of the amino-terminal
      region of the gamma-chain to the structural and functional properties of Hb F as
      compared to human normal adult hemoglobin (Hb A). Substitutions in the N-terminal
      region of Hb A have shown this region to be important to its structural and
      functional properties. Recent studies of recombinant mutants of Hb A with gamma
      chain mutations have been used to probe the significance of the N-terminal
      sequence to the properties of Hb F. One of these mutants of Hb A, called rHb
      Felix, contains eight substitutions in the N-terminal region of the beta-chain
      corresponding to the sequence of the gamma-chain in that region [Dumoulin et al.
      (1998) J. Biol. Chem. 273, 35032-35038]. rHb Felix exhibits a 2,3
      bisphosphoglycerate (2,3-BPG) response like that of Hb A, but its tetramer-dimer
      dissociation constant is similar to that of Hb F. In contrast, rHb Oscar contains
      a gamma-chain with eight mutations at the N-terminal end corresponding to the
      sequence of the beta-chain of Hb A in that region. (1)H NMR studies of rHb Oscar
      indicate a global structure like that of Hb F. rHb Oscar is not as stable against
      alkaline denaturation as Hb F but is more stable than Hb A, and it exhibits a
      stronger response to 2,3-BPG and inositol hexaphosphate as compared to Hb F. The
      2,3-BPG effect in rHb Oscar also appears to be slightly enhanced compared to that
      in Hb A. Subzero isoelectric focusing experiments suggest that rHb Oscar does not
      have dissociation properties like those of Hb A. These results along with those
      of rHb Felix illustrate that the effects of the N-terminal region on structure
      and function of the Hb molecule are complicated by interactions with the rest of
      the molecule that are not yet well defined. However, studies of complementary
      mutations of Hb A and Hb F may eventually help to define such interactions and
      lead to a better understanding of the relationship between the amino acid
      sequence and the properties of the Hb molecule.

PMID- 11580293
TI  - Solution conformation of human apolipoprotein C-1 inferred from proline
      mutagenesis: far- and near-UV CD study.
AB  - Solution structure of lipid-free apolipoprotein C-1 (apoC-1, 6.6 kD) was analyzed
      by circular dichroism (CD) of 15 mutants containing single Pro or Ala
      substitutions in predicted alpha-helical regions. While the majority of Pro
      substitutions induce complete (L11P, L18P, R23P, I29P, M38P, W41P, T45P) or
      partial (G15P, L34P) helical unfolding, similar substitutions at other sites
      (A7P, Q31P, V49P, L53P) do not cause large changes in the secondary structure or
      stability. The results suggest that lipid-free apoC-1 is comprised of two dynamic
      helices that are stabilized by interhelical interactions and are connected by a
      short linker containing residues 30-33. We propose that the minimal folding unit
      in the lipid-free state of this and other exchangeable apolipoproteins comprises
      the helix-turn-helix motif formed of four 11-mer sequence repeats. Comparison of
      the helical content in lipid-free and lipid-bound apoC-1 suggests that lipid
      binding shifts the conformational equilibrium toward preexisting highly helical
      conformation. Remarkably, near-UV CD spectra of wild type and mutant apoC-1 are
      not significantly altered upon thermal or chemical unfolding and thus result from
      residual aromatic clustering that is retained in the unfolded state. Correlation
      of far- and near-UV CD of the mutant peptides suggests that the hydrophobic
      cluster containing W41 is essential for the helical stability and may form a
      helix nucleation site in apoC-1.

PMID- 11580294
TI  - Effect of surface charges on the rates of intermolecular electron-transfer
      between de novo designed metalloproteins.
AB  - A de novo designed coiled-coil metalloprotein was prepared that uses
      electrostatic interactions to control both its conformational and bimolecular
      electron-transfer properties. The title protein exists as a coiled-coil
      heterodimer of the [Ru(trpy)(bpy)-KK(37-mer)] and [Ru(NH(3))(5)-EE(37-mer)]
      polypeptides which is formed by interhelix electrostatic attractions. Circular
      dichroism studies show that the electrostatic heterodimer has K(d) = 0.19 +/-
      0.03 microM and is 96% helical at high concentrations. Intercomplex electron
      transfer reactions were studied that involve the [Ru(NH(3))(5)-H21](2+) electron
      donor and the [Ru(trpy)(bpy)-H21](3+) electron-acceptor belonging to different
      electrostatic dimers. An important feature of the designed metalloprotein is its
      two cationic redox centers embedded within protein surfaces having opposite
      charge. Thus, the Ru(II)(NH(3))(5)-H21 site was placed on the surface of one
      chain of the coiled-coil which was made to be positively charged, and the
      Ru(III)(trpy)(bpy)-H21 site was placed on the surface of the other chain which
      was negatively charged. The rates of intermolecular electron-transfer increased
      from (1.9 +/- 0.4) x 10(7) M(-1) s(-1) to (3.7 +/- 0.5) x 10(7) M(-1) s(-1) as
      the ionic strength was increased from 0.01 to 0.20 M. This indicates that the
      electrostatic repulsion between the ruthenium centers dominates the kinetics of
      these reactions. However, the presence of the oppositely charged protein surfaces
      in the coiled-coils creates an electrostatic recognition domain that
      substantially ameliorates the effects of this repulsion.

PMID- 11580295
TI  - Allosteric regulation provides a molecular mechanism for preferential utilization
      of the fully assembled dolichol-linked oligosaccharide by the yeast
      oligosaccharyltransferase.
AB  - The oligosaccharyltransferase (OST) preferentially utilizes the fully assembled
      dolichol-linked oligosaccharide Glc(3)Man(9)GlcNAc(2)-PP-Dol as the donor for N
      linked glycosylation of asparagine residues in N-X-T/S consensus sites in newly
      synthesized proteins. A wide variety of assembly intermediates (Glc(0-2)Man(0
      9)GlcNAc(2)-PP-Dol) can serve as the donor substrate for N-linked glycosylation
      of peptide acceptor substrates in vitro or of nascent glycoproteins in mutant
      cells that are defective in donor substrate assembly. A kinetic mechanism that
      can account for the selection of the fully assembled donor substrate from a
      complex mixture of dolichol-linked oligosaccharides (OS-PP-Dol) has not been
      elucidated. Here, the steady-state kinetic properties of the OST were
      reinvestigated using a proteoliposome assay system consisting of the purified
      yeast enzyme, near-homogeneous preparations of a dolichol-linked oligosaccharide
      (Glc(3)Man(9)GlcNAc(2)-PP-Dol or Man(9)GlcNAc(2)-PP-Dol) and an (125)I-labeled
      tripeptide as the acceptor substrate. The K(m) of the OST for the acceptor
      tripeptide was only slightly enhanced when Glc(3)Man(9)GlcNAc(2)-PP-Dol was the
      donor substrate relative to when Man(9)GlcNAc(2)-PP-Dol was the donor substrate.
      Evaluation of the kinetic data for both donor substrates showed deviations from
      typical Michaelis-Menten kinetics. Sigmoidal saturation curves, Lineweaver-Burk
      plots with upward curvature, and apparent Hill coefficients of about 1.4
      suggested a substrate activation mechanism involving distinct regulatory
      (activator) and catalytic binding sites for OS-PP-Dol. Results of competition
      experiments using either oligosaccharide donor as an alternative substrate were
      also consistent with this hypothesis. We propose that binding of either donor
      substrate to the activator site substantially enhances Glc(3)Man(9)GlcNAc(2)-PP
      Dol occupancy of the enzyme catalytic site via allosteric activation.

PMID- 11580296
TI  - Biochemical characterization of a phosphinate inhibitor of Escherichia coli MurC.
AB  - The bacterial UDP-N-acetylmuramyl-L-alanine ligase (MurC) from Escherichia coli,
      an essential, cytoplasmic peptidoglycan biosynthetic enzyme, catalyzes the ATP
      dependent ligation of L-alanine (Ala) and UDP-N-acetylmuramic acid (UNAM) to form
      UDP-N-acetylmuramyl-L-alanine (UNAM-Ala). The phosphinate inhibitor 1 was
      designed and prepared as a multisubstrate/transition state analogue. The compound
      exhibits mixed-type inhibition with respect to all three enzyme substrates (ATP,
      UNAM, Ala), suggesting that this compound forms dead-end complexes with multiple
      enzyme states. Results from isothermal titration calorimetry (ITC) studies
      supported these findings as exothermic binding was observed under conditions with
      free enzyme (K(d) = 1.80-2.79 microM, 95% CI), enzyme saturated with ATP (K(d) =
      0.097-0.108 microM, 95% CI), and enzyme saturated with the reaction product ADP
      (K(d) = 0.371-0.751 microM, 95% CI). Titrations run under conditions of
      saturating UNAM or the product UNAM-Ala did not show heat effects consistent with
      competitive compound binding to the active site. The potent binding affinity
      observed in the presence of ATP is consistent with the inhibitor design and the
      proposed Ordered Ter-Ter mechanism for this enzyme; however, the additional
      binding pathways suggest that the inhibitor can also serve as a product analogue.

PMID- 11580297
TI  - A new spectroscopic approach to examining the role of disulfide bonds in the
      structure and unfolding of soybean trypsin inhibitor.
AB  - Although it is well-known that disulfide bonds stabilize the secondary structure
      of many proteins, it is difficult to directly probe both disulfide bond
      formation/breakage and the resulting secondary structural changes during the
      course of the protein folding/unfolding process. In this work, we have used a
      new, real-time spectroscopic approach to examine how the reduction of two
      disulfide bonds affects the secondary structure of soybean trypsin inhibitor
      (STI). The disulfide bonds are reduced with tris(2-carboxyethyl)phosphine (TCEP)
      at 40 degrees C, and the reduction process is probed in real-time using sulfur X
      ray absorption spectroscopy. Circular dichroism (CD) and Fourier transform
      infrared (FTIR) spectroscopies are used concurrently to determine the structural
      changes caused by reduction of the disulfide bonds. Results demonstrate a
      noncooperative reduction of the two disulfide bonds within 5 min, likely because
      they are located on the surface of the protein. The unfolding of STI lags behind;
      dramatic changes are not observed until 60-90 min after the reduction was
      initiated. The CD and FTIR spectra indicate a decrease in the amount of extended
      (hydrated) coil, suggesting that the STI structure slowly collapses after the
      disulfide bonds are reduced. Thus, although the disulfide bonds are not located
      near the active site of STI, they play a crucial role in stabilizing the protein
      structure, which is necessary to sustain enzymatic activity.

PMID- 11580298
TI  - A face on transmembrane segment 8 of the lactose permease is important for
      transport activity.
AB  - Previous work on the lactose permease of Escherichia coli has shown that
      mutations along a face of predicted transmembrane segment 2 (TMS-2) play a
      critical role in conformational changes associated with lactose transport [Green,
      A. L., Anderson, E. J., and Brooker, R. J. (2000) J. Biol. Chem. 275, 23240
      23246]. In the current study, mutagenesis was conducted along the side of
      predicted TMS-8 that contains the first amino acid in the conserved loop 8/9
      motif. Several substitutions at positions 261, 265, 272, and 276 were markedly
      defective for downhill lactose transport although these mutants were well
      expressed. Substitutions along the entire side of TMS-8 containing the first
      amino acid in the loop 8/9 motif displayed defects in uphill lactose transport.
      Again, substitutions at positions 261, 265, 268, 272, and 276 were the most
      defective, with several of these mutants showing no lactose accumulation against
      a gradient. According to helical wheel plots, Phe-261, Thr-265, Gly-268, Asn-272,
      and Met-276 form a continuous stripe along one face of TMS-8. These results are
      discussed according to our hypothetical model, in which the two halves of the
      protein form a rotationally symmetrical dimer. In support of this model,
      alignment of predicted TMS-2 and TMS-8 shows an agreement between the amino acid
      residues in these transmembrane segments that are critical for lactose transport
      activities.

PMID- 11580300
TI  - Clinical potential of cyclo-oxygenase-2 inhibitors.
AB  - On the basis of their reduced potential to cause injury to the gastroduodenal
      mucosa, cyclo-oxygenase (COX)-2-selective inhibitors were developed and marketed
      as a safer alternative to traditional nonsteroidal anti-inflammatory drugs
      (NSAIDs). This manuscript reviews the major steps leading to the introduction of
      COX-2-selective inhibitors into clinical practice, from the identification of the
      COX isoenzymes to their various roles in physiological and pathological
      processes. The available data show that COX-2 inhibitors have a favourable safety
      profile and are at least as effective as traditional NSAIDs for the treatment of
      pain and inflammatory conditions with a reduced incidence of gastrointestinal
      complications. Emerging evidence points to new and unanticipated effects from
      these agents. COX-2 inhibition appears to play an important role in the
      modulation of intestinal polyposis and colorectal carcinogenesis. Additionally,
      COX-2 expression may be associated with inflammatory responses leading to the
      occurrence of Alzheimer's disease and potentially, COX-2 inhibitors could be used
      to retard the progression of this condition. However, by decreasing prostacyclin
      production, COX-2 inhibitors may lead to increased prothrombotic activity and
      increase the risk of cardiovascular events. Until further large-scale prospective
      studies are performed, and the magnitude of these potential risks is quantified,
      COX-2 inhibitors should be used with caution in patients at risk for
      cardiovascular morbidity.

PMID- 11580302
TI  - Immunological approaches to the treatment of spinal cord injury.
AB  - The innate and adaptive arms of the immune system, represented principally by
      macrophages and by T and B cells, respectively, provide body tissues with
      mechanisms of defence, protection and repair. In the central nervous system
      (CNS), probably because of its status of 'immune privilege', any immune activity
      has long been viewed as detrimental. Recent studies have provided evidence,
      however, that immune activity after traumatic CNS injury may have a beneficial
      effect, manifested by promotion of regeneration and reduction in the secondary
      degeneration of neurons that escaped direct injury. Rigorous regulation of immune
      system activity allows the individual to derive the benefit of such
      neuroprotection without the risk of detrimental side effects. Recently, our
      research group found a way to boost the T-cell-mediated autoimmune protection
      while avoiding the risk of autoimmune disease.

PMID- 11580301
TI  - Management of hepatitis C virus-related arthritis.
AB  - Hepatitis C virus (HCV) infection is often associated with extrahepatic
      manifestations among which arthropathy is common, affecting up to 20% of HCV
      infected individuals. This arthropathy is to be distinguished from the more
      superficially prominent myalgias and fatigue. HCV-related arthritis is commonly
      presented as rheumatoid-like, symmetrical inflammatory polyarthritis involving
      mainly small joints, or, less commonly, as mono- or oligoarthritis, usually of
      the large joints. HCV arthritis usually runs a relatively benign course that, in
      contrast to 'true' rheumatoid arthritis (RA), is typically non-deforming and is
      not associated with articular bony erosions. In addition, unlike 'classic' RA,
      erythrocyte sedimentation rate is elevated only in about half of the patients and
      subcutaneous nodules are absent. In about two-thirds of the affected individuals
      morning stiffness may be severe, resolving after more than an hour. Several
      pathogenetic mechanisms may be involved: HCV arthritis may be part of the
      syndrome of mixed cryoglobulinaemia, or may be directly or indirectly mediated by
      HCV. Such possible, but yet not proven, mechanisms include direct invasion of
      synovial cells by the virus eliciting local inflammatory response, cytokine
      induced disease or immune complex disease, particularly in genetically
      susceptible individuals. The diagnosis of HCV arthritis in patients with positive
      rheumatoid factor and chronic inflammatory polyarthritis may be difficult.
      Positive HCV antibody and HCV RNA, and the absence of bony erosions, subcutaneous
      nodules and antikeratin antibodies, may be useful in distinguishing between HCV
      related arthritis and RA. The optimal treatment of HCV-related arthritis has not
      yet been established. Concerns may be raised regarding the use of
      immunosuppressive or potentially hepatotoxic drugs. However, it may be suggested
      that once the diagnosis of HCV-associated arthritis is made, combination
      antiviral treatment with interferon-alpha and ribavirin should be initiated as
      part of the therapeutic armamentarium. Low dose oral corticosteroids,
      nonsteroidal anti-inflammatory drugs, hydroxychloroquine or sulfasalazine in
      addition to the antiviral therapy can be used to control arthritis-related
      symptoms. Some patients may need long term anti-inflammatory treatment in various
      combinations, along with antiviral therapy. In patients with severe, disabling or
      life-threatening cryoglobulinaemia-related symptoms refractory to antiviral or
      anti-inflammatory treatment, high dose corticosteroids (including pulse therapy)
      and/or plasmapheresis may be needed.

PMID- 11580303
TI  - Role of the complement system in ischaemic heart disease: potential for
      pharmacological intervention.
AB  - The complement system is an innate, cytotoxic host defence system that normally
      functions to eliminate foreign pathogens. However, considerable evidence suggests
      that complement plays a key role in the pathophysiology of ischaemic heart
      disease (IHD). Experimental models of acute myocardial infarction (MI) and
      autopsy specimens taken from acute MI patients demonstrate that complement is
      selectively deposited in areas of infarction. Furthermore, inhibition of
      complement activation or depletion of complement components prior to myocardial
      reperfusion has been shown to reduce complement-mediated tissue injury in
      numerous animal models. IHD remains a leading cause of patient morbidity and
      mortality. Considerable effort in recent years has therefore been directed by
      biotechnology and pharmaceutical industries towards the development of novel,
      human complement inhibitors. Proposed anticomplement therapeutic strategies
      include the administration of naturally occurring or recombinant complement
      regulators, anticomplement monoclonal antibodies, and anticomplement receptor
      antagonists. Although data regarding the effectiveness of anticomplement therapy
      in humans is limited at present, a number of novel anticomplement therapeutic
      strategies are currently in clinical trials. The role of complement in IHD and
      potential for pharmacological intervention is reviewed.

PMID- 11580304
TI  - Recombinant relaxin: a review of pharmacology and potential therapeutic use.
AB  - Use of recombinant relaxin in the treatment of systemic sclerosis (or
      scleroderma) has been explored and determined as ineffective. However, continued
      research has revealed that relaxin is not limited to its role as a hormone.
      Relaxin has also been shown to decrease collagen formation and secretion,
      increase collagenase production, influence renal vasodilation, increase vascular
      endothelial growth factor expression and angiogenesis, promote dilation of blood
      vessels, and inhibit release of histamine. Further studies to discover other
      potential uses of relaxin are well-justified.

PMID- 11580305
TI  - Perspectives on gene therapy for cystic fibrosis airway disease.
AB  - Since the discovery of the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene nearly 12 years ago, cystic fibrosis (CF) has become one of the most
      intensively investigated monogenetic disorders considered approachable by gene
      therapy. This has resulted in over 20 clinical trials currently under way,
      concluded or awaiting approval. Despite the initial promise of gene therapy for
      CF, and the demonstration of successful gene transfer to the nose and airways of
      individuals, it has not so far been as effective as initially projected. Here we
      discuss the rationale behind CF gene therapy and dissect the vast array of
      literature representing the work that ultimately brought about the current phase
      I/II clinical trials. In the context of human trials, we review the limitations
      of current vector systems for CF gene therapy. We come to the conclusion that at
      present none of the application methods and vector systems are able to achieve
      the level and persistence of CFTR gene expression in the affected epithelia of CF
      patients that is required for therapeutic success. We also outline the challenges
      that must be overcome and describe some of the novel approaches to be taken in
      order to attain the curative therapy that was originally envisaged for this
      disease.

PMID- 11580306
TI  - Choosing the right dose of antipsychotics in schizophrenia: lessons from
      neuroimaging studies.
AB  - Despite vast clinical experience with antipsychotics, there is no broad consensus
      on the doses of these substances that should be administered. Currently, most
      antipsychotics are administered empirically according to clinical dose-finding
      studies, in which arbitrarily selected doses were tested to find the "most
      efficient" dose range in a patient population, with no regard for the molecular
      effects of the tested drug. Brain imaging studies using nuclear medical
      techniques, such as positron emission tomography (PET) or single photon emission
      computed tomography (SPECT), can now provide a rationale for doses, directly
      derived from the central effects of the drugs on neurotransmitter receptors
      measured in vivo. PET results indicate that occupancy of at least 65% of dopamine
      D(2) receptors is needed for clinical response to antipsychotics, and that
      occupancy rates exceeding 72 and 78% are associated with a high risk for
      elevation of prolactin levels and motor adverse effects, respectively. For
      example, clinical studies with haloperidol do not point to an advantage of
      dosages exceeding 5 mg/day. The relevance of D(2) receptor occupancy for drug
      administration is also borne out by studies relating the effects of
      antipsychotics to their D(2) receptor occupancy in relevant animal models. Taken
      together, neuroimaging and clinical studies, as well as animal models, provide a
      rationale for the use of relatively low doses of typical antipsychotics and
      equivalent doses of novel antipsychotics. The lower risk of adverse effects with
      appropriate doses of antipsychotics may further enhance compliance and outcome.
      This seems to be particularly important in individuals experiencing a first
      episode of schizophrenia, as they appear to be especially responsive to
      pharmacotherapy and quite sensitive to adverse effects.

PMID- 11580307
TI  - Can anticonvulsant drug therapy "cure" epilepsy?
AB  - There is now evidence to show that, as time passes, epilepsy, even if untreated,
      tends to undergo spontaneous remission in a significant proportion of patients.
      The question therefore arises as to whether anticonvulsant drug therapy increases
      this chance of the patient with epilepsy ultimately entering a terminal remission
      which continues after the treatment is withdrawn, i.e. whether anticonvulsant
      drug therapy itself may sometimes cure epilepsy. There are no well-designed
      studies available in the literature that provide a clear answer to this question.
      However, data from a number of investigations carried out for other purposes can
      be used to see whether contemporary anticonvulsant drug therapy is associated
      with higher rates of expected untreated terminal remission than those that apply
      for never-treated patients with epilepsy, or for those whose anticonvulsant
      treatment has probably been inadequate for various social or historical reasons.
      Despite the admitted uncertainties inherent in drawing conclusions from such
      material, there appears to be a reasonably consistent tendency for contemporary
      anticonvulsant drug treatment to be associated with a greater chance of achieving
      probable cure of epilepsy. Therefore it would appear premature to take the view
      that contemporary anticonvulsant drug therapy does no more than suppress
      epileptic seizures until epilepsy remits spontaneously, or fails to remit, with
      the passing of time.

PMID- 11580308
TI  - Dementia in patients undergoing long-term dialysis: aetiology, differential
      diagnoses, epidemiology and management.
AB  - Dementia in patients undergoing long-term dialysis has not been clearly defined;
      however, four different entities have been described. Uraemic encephalopathy is a
      complication of uraemia and responds well to dialysis. Dialysis encephalopathy
      syndrome, the result of acute intoxication of aluminium caused by the use of an
      aluminium-containing dialysate, was a common occurrence prior to 1980. However,
      using modern techniques of water purification, such acute intoxication can now be
      avoided. Dialysis-associated encephalopathy/dementia (DAE) is always associated
      with elevated serum aluminium levels. Pathognomonic morphological changes in the
      brain have been described, but the mechanism for the entry of aluminium into the
      CNS is incompletely understood. The mechanisms involved in the pathogenesis of
      the neurotoxicity associated with aluminium are numerous. Although only a very
      small fraction of ingested aluminium is absorbed, the continuous oral aluminium
      intake from aluminium-based phosphate binders, and also of dietary or
      environmental origin, is responsible for aluminium overload in dialysis patients.
      Age-related dementia, especially vascular dementia, occurs in patients undergoing
      long-term dialysis as frequently as it does in the general population. The
      differential diagnoses of dialysis-associated dementias should include
      investigation for metabolic encephalopathies, heavy metal or trace element
      intoxications, and distinct structural neurological lesions such as subdural
      haematoma, normal pressure hydrocephalus, stroke and, particularly, hypertensive
      encephalopathy and multi-infarct dementia. To prevent DAE, dietary training
      programmes should aim to achieve the lowest phosphate intake and pharmacological
      tools should be used to keep serum phosphate levels below 2 mmol/L. To prevent
      vascular dementia, lifestyle modification should be undertaken, including optimal
      physical activity and fat intake, nicotine abstinence, and targeting optimal
      blood glucose, cholesterol and triglyceride levels, and blood pressure, to those
      outlined in current recommendations.

PMID- 11580311
TI  - External noise synchronizes forced oscillators.
AB  - Periodic pulsatile perturbation of nonlinear oscillators generates phase-locking,
      quasiperiodic, and chaotic responses. This work shows that the application of
      external noise to ensembles of such forced systems can synchronize oscillations,
      even in regimes where neither the noise nor the periodic forcing, when applied
      alone, would lead to such a phenomenon.

PMID- 11580309
TI  - Comparative efficacy and tolerability of drug treatments for bipolar disorder.
AB  - Lithium has been the backbone of treatment for bipolar disorder for several
      decades, although recent advances have identified a number of other medications
      that have efficacy in treating various phases of the illness. These include the
      antiepileptic drugs valproate semisodium (divalproex sodium) and carbamazepine
      and some new antiepileptic drugs (e.g. lamotrigine and topiramate), and the
      atypical antipsychotics (e.g. olanzapine, clozapine and risperidone).
      Conventional antipsychotics continue to be used frequently in bipolar disorder,
      although they may be somewhat less effective than other treatments. Otherwise, to
      date, none of these treatments have been shown to be consistently more effective
      than any other, so that drug adverse effects and tolerability often dictate which
      agents are used in an individual patient. Drugs commonly used for the treatment
      of bipolar disorder are generally tolerated by most patients in large samples.
      However, the unique adverse effect signature of a drug will often suggest that it
      will be less tolerable in some patients than in others. Identifying a specific
      treatment for a specific patient requires a careful individualised assessment of
      the risk of adverse effects for that patient's unique circumstances.

PMID- 11580313
TI  - Stochastic resonant memory storage device.
AB  - We show that an extended system operating in the regime of stochastic resonance
      can act as a short-term memory device. The system under study is a ring of
      overdamped bistable oscillators coupled directionally, being each also subject to
      an external source of Gaussian white noise (the noise sources are independent). A
      single oscillator is driven by an external periodic force, assumed to act only
      over the time that the signal takes to traverse the whole ring. A traveling wave
      is then found to be transmitted several times along the ring with a small
      damping, provided that the driven oscillator operates in a regime close to
      stochastic resonance. If noise is suppressed from any oscillator of the chain,
      the traveling wave is immediately damped. The ring is thus found to act as a
      short-term memory device in which the stored information (one bit, corresponding
      to the presence or absence of the external driving) is sustained by noise during
      a characteristic time T(mem).

PMID- 11580312
TI  - Generic noise-enhanced coding in neuronal arrays.
AB  - We demonstrate that, in a parallel array of model neurons, the optimizing
      influence of internal noise on the global information is far greater than that
      reported for a single neuron. In particular, stochastic resonance (SR) effects,
      that optimize information transmission, occur independent of stimulus level or
      the setting of the neural threshold. We further show that adjusting the threshold
      to maximize information transmission does not remove SR effects. Consequently,
      and in contrast to a single neuron, in neuronal arrays noise appears to be an
      essential element of an optimal coding strategy.

PMID- 11580314
TI  - Stochastic processes with finite correlation time: modeling and application to
      the generalized Langevin equation.
AB  - The kangaroo process (KP) is characterized by various forms of covariance and can
      serve as a useful model of random noises. We discuss properties of that process
      for the exponential, stretched exponential, and algebraic (power-law)
      covariances. Then we apply the KP as a model of noise in the generalized Langevin
      equation and simulate solutions by a Monte Carlo method. Some results appear to
      be incompatible with requirements of the fluctuation-dissipation theorem because
      probability distributions change when the process is inserted into the equation.
      We demonstrate how one can construct a model of noise free of that difficulty.
      This form of the KP is especially suitable for physical applications.

PMID- 11580315
TI  - Self-organized network of fractal-shaped components coupled through statistical
      interaction.
AB  - A dissipative dynamics is introduced to generate self-organized networks of
      interacting objects, which we call coupled-fractal networks. The growth model is
      constructed based on a growth hypothesis in which the growth rate of each object
      is a product of the probability of receiving source materials from faraway and
      the probability of receiving adhesives from other grown objects, where each
      object grows to be a random fractal if isolated, but connects with others if
      glued. The network is governed by the statistical interaction between fractal
      shaped components, which can only be identified in a statistical manner over
      ensembles. This interaction is investigated using the degree of correlation
      between fractal-shaped components, enabling us to determine whether it is
      attractive or repulsive.

PMID- 11580310
TI  - Pharmacotherapy of malignant astrocytomas of children and adults: current
      strategies and future trends.
AB  - This article reviews the conceptual progression in the pharmacological therapy of
      malignant astrocytoma (MA) over the past decade, and its future trends. It is a
      selective rather than an exhaustive inventory of literature citations. The
      experience of the Brain Tumour Cooperative Group (BTCG) and earlier phase III
      trials are summarised to place subsequent phase II and I studies of single and
      combination agent chemotherapy in perspective. The BTCG experience of the 1970s
      to 1980s may be summarised to indicate that external beam radiotherapy (EBRT) is
      therapeutic, although not curative, and not further improved upon by altering
      fractionation schedules, or the addition of radioenhancers. Whole brain and
      reduced whole brain EBRT with focal boost were comparable regimens. Nitrosourea
      based, adjuvant chemotherapy provided a modest improvement in survival among
      adult patients, which was comparable with that of other single drugs or multidrug
      regimes. The multiagent schedules, however, had a correspondingly higher toxicity
      rate. Intra-arterial administration was associated with significant risk, which
      conferred no therapeutic advantage. The trend of the past decade has been towards
      multiagent chemotherapy although its benefit cannot be predicted from the classic
      prognostic factors. Published experience with investigational trials utilising
      myeloablative chemotherapy with autologous bone marrow or peripheral blood stem
      cell haemopoietic support, drug delivery enhancement methods and radiosensitisers
      is critically reviewed. None of these approaches have achieved wide-spread
      acceptance in the treatment of adult patients with MA. Greater attention is
      placed on recent 'chemoradiotherapy' trials, which attempt to integrate and
      maximise the cytoreductive potential of both modalities. This approach holds
      promise as an effective means to delay or overcome the evolution of tumour
      resistance, which is probably one of the dominant determinants of prognosis.
      However, the efficacy of this approach remains unproven. New chemotherapeutic
      agents as well as biological response modifiers, protein kinase inhibitors,
      angiogenesis inhibitors and gene therapy are also discussed; their role in the
      therapeutic armamentarium has not been defined.

PMID- 11580316
TI  - Thermodynamic properties of a polydisperse system.
AB  - We use the virial theorem to derive a closed analytic form of the Helmholtz free
      energy for a polydisperse system of sticky hard spheres (SHS) within the mean
      spherical model (MSM). To this end we calculate the free energy of the MSM for an
      N-component mixture of SHS via the virial route and apply to it-after imposing a
      Lorentz-Berthelot type rule on the interactions-the stochastic (i.e.,
      polydisperse) limit. The resulting excess free energy of this polydisperse system
      is of the truncatable moment free energy format. We also discuss the
      compressibility and the energy routes.

PMID- 11580317
TI  - Connecting the vulcanization transition to percolation.
AB  - The vulcanization transition is addressed via a minimal replica-field-theoretic
      model. The appropriate long-wavelength behavior of the two- and three-point
      vertex functions is considered diagrammatically, to all orders in perturbation
      theory, and identified with the corresponding quantities in the Houghton-Reeve
      Wallace field-theoretic approach to the percolation critical phenomenon. Hence,
      it is shown that percolation theory correctly captures the critical phenomenology
      of the vulcanization transition associated with the liquid and critical states.

PMID- 11580318
TI  - Experimental observation of stochastic resonance in a linear electronic array.
AB  - We report the experimental observation of array-enhanced stochastic resonance,
      spatiotemporal synchronization, and noise-enhanced propagation in a simple
      coupled linear array of bistable electronic triggers. In addition, we highlight
      an analogy between charge density wave (CDW) like conductivity and spatiotemporal
      synchronization in stochastic resonances, several aspects of which are supported
      by the experimental evidence presented here. This may prove to be important in
      the understanding of nonlinear conductivity in CDW solids.

PMID- 11580319
TI  - Criticality of natural absorbing states.
AB  - We study a recently introduced ladder model that undergoes a transition between
      an active and an infinitely degenerate absorbing phase. In some cases the
      critical behavior of the model is the same as that of the branching-annihilating
      random walk with N>/=2 species both with and without hard-core interaction. We
      show that certain static characteristics of the so-called natural absorbing
      states develop power-law singularities that signal the approach of the critical
      point. These results are also explained using random-walk arguments. In addition
      to that we show that when dynamics of our model is considered as a minimum
      finding procedure, it has the best efficiency very close to the critical point.

PMID- 11580320
TI  - Classical diffusion in channels with a spatially varying cross-section.
AB  - We study the diffusion of classical particles in channels with varying
      boundaries. The problem is characterized by the Neumann boundary condition (zero
      normal current) in contrast to the Dirichlet boundary condition (zero function)
      for "quantum confinement" problems. Eliminating transverse modes, we derive an
      effective diffusion equation that describes particle propagation in the space of
      reduced dimension in the presence of a frozen drift field. The latter stems from
      boundary variations of the original boundary problem. Boundary variations may
      thus result in an appreciable change of the particle transport and, in
      particular, in a nonlinear response to an external field. We show also that there
      is a difference between the nonlinear responses of open and closed channels.

PMID- 11580321
TI  - Analytical estimate of percolation for multicomponent fluid mixtures.
AB  - The size of a dense region of a particular constituent (L(s)) in a nonuniform
      distribution of particles generated in a multicomponent fluid mixture can develop
      under certain conditions. If both the attractive force between an L(s) particle
      and a particle of the other constituents (L(c)(s)) and the attractive force
      between L(c)(s) particles are much weaker than that between L(s) particles, then
      the percolation due to the growth of the dense region of L(s) particles can
      hardly be affected by the addition of L(c)(s) particles into the fluid mixture.
      In that case, dense regions composed of L(c)(s) particles can be formed
      passively. To derive these results, it is assumed that such a dense region is an
      ensemble of particles bound to each other as particle pairs that satisfy the
      condition E(ij)+u(ij)(r)</=0, where E(ij) is the relative kinetic energy for i
      and j particles and u(ij)(r) is the pair potential. The percolation in the fluid
      mixture can be estimated analytically. According to the pair connectedness
      function P(ij)(r) derived for evaluating the percolation, the probability that an
      L(s) particle is located near another L(s) particle can be insensitive to the
      addition of L(c)(s) particles. The magnitude of P(ij)(r) can be maximized for a
      pair of i-j particles interacting with the most strongly attractive force having
      the largest value of the effective ranges in a fluid mixture system. These
      particles can contribute to making the phase behavior of the fluid mixture
      complicated.

PMID- 11580322
TI  - Dynamics of inherent structure in supercooled liquids near kinetic glass
      transition.
AB  - We present a description of the dynamics of a supercooled binary Lennard-Jones
      liquid in term of the potential landscape of the system. The slowing down of the
      dynamics in supercooled liquids near the kinetic glass transition is related to
      the existence of basins in the potential landscape. The inherent structures that
      are the local potential minima in the configuration space obtained by a quench
      process are employed to represent the configurations of the basins. We present
      time correlation functions of the inherent structure, both the self and the
      coherent part, as a function of wave vector. We also calculated the mean-square
      displacement, and the non-Gaussian parameter of the van Hove self-correlation
      function. Compared with the dynamics of original configurations, the short-time
      relaxation has almost been eliminated by the quench process. However, the long
      time alpha relaxations remain essentially the same. We conclude that the long
      time alpha relaxation is the result of cross-basin transition in the potential
      landscape in the configuration space.

PMID- 11580323
TI  - Bulk and shear viscosities in lattice Boltzmann equations.
AB  - Lattice Boltzmann equations (LBE) are a useful tool for simulating the
      incompressible Navier-Stokes equations. However, LBE actually simulate a
      compressible but usually isothermal fluid at some small but finite Mach number.
      There has been recent interest in using LBE at larger, but still subsonic, Mach
      numbers, for which the viscous terms in the resulting momentum equation depart
      appreciably from those in the compressible Navier-Stokes equations. In
      particular, the isothermal constraint implies a nonzero "bulk" viscosity in
      addition to the usual shear viscosity. This difficulty arises at the level of the
      isothermal continuum Boltzmann equation prior to discretization. A remedy is
      proposed, and tested in numerical experiments with decaying sound waves.
      Conversely, an enhanced bulk viscosity is found useful for identifying or
      suppressing artifacts in under-resolved simulations of supposedly incompressible
      shear flows.

PMID- 11580324
TI  - Simple model for a two-component gas flow in the presence of macroscopic
      scatterers.
AB  - The nonequilibrium state of a two-component gas mixture in the presence of
      macroscopic scatterers is investigated. The general solution of a set of the
      kinetic equations is obtained in the operator form. The model presentation of the
      collision operator is derived in the spirit of the Bhatnagar-Gross-Krook method.
      The rigorous solution of a set of the derived model kinetic equations is found.

PMID- 11580325
TI  - Active control of oscillatory thermocapillary convection.
AB  - Active control of oscillatory thermocapillary flow was applied in an open
      cylindrical container filled with silicone oil. Thermocapillary convection was
      driven by imposing a radial temperature gradient on a flat free surface. The
      control was realized by locally heating the surface at a single position using
      the local temperature signal at a different position fed back through a simple
      algorithm. Significant attenuation of the oscillation was achieved in a wide
      range of supercritical Marangoni numbers, with the best performance in the weakly
      non-linear regime. Simultaneously measuring the temperature oscillation at two
      positions gives us a good insight in how the control influences the whole
      temperature field on the free surface. Quantitative analysis was done to
      characterize the optimal feedback amplification and the required power.

PMID- 11580326
TI  - Correlation between bulk stresses and interparticle contact forces in fine
      powders.
AB  - We present measurements of the tensile strength as a function of the
      consolidation stress for a set of fine cohesive powders (xerographic toners) of
      12.7 microm particle size and with a range of concentration of submicron fumed
      silica as flow control additive. This additive is well known for its ability to
      control interparticle adhesion force. Parallel measurements using an atomic force
      microscope have been carried out on the adhesion force between two individual
      grains as a function of a controlled previous load force. The effect of the
      additive on the tensile strength and adhesion force is analyzed. We have found a
      good correlation between bulk stresses and adhesion forces between individual
      particles. This correlation is compatible with the existence of a subnetwork of
      force chains.

PMID- 11580327
TI  - Scaling relations for granular flow in quasi-two-dimensional rotating cylinders.
AB  - An experimental study of the flow of different materials (steel balls, glass
      beads, and sand) in quasi-two-dimensional rotating cylinders is carried out using
      flow visualization. The flow in the rotating cylinder comprises of a thin-flowing
      surface layer with the remaining particles rotating as a fixed bed. Experimental
      results indicate that the scaled layer thickness increases with increasing Froude
      number (Fr=omega(2)R/g, where omega is the angular speed, R is the cylinder
      radius, and g the acceleration due to gravity) and with increase in size ratio
      (s=d/R, where d is the particle diameter). The free surface profile, is nearly
      flat at low Fr and becomes increasingly S shaped with increasing Fr. The layer
      thickness profiles, which are symmetric at low Fr become skewed at high values of
      Fr and small s. The dynamic angles of repose for all the materials studied show a
      near-linear increase with rotational speed (omega). Scaling analysis of the
      experimental data shows that the shape of the scaled surface profiles and the
      scaled layer thickness profiles are nearly identical when Froude number and size
      ratio are held constant, for each material. The surface profiles and layer
      thickness profiles are also found to be nearly independent of the material used.
      The dynamic angle of repose (beta), however, does not scale with Fr and s and
      depends on the particle properties. The experimental results are compared to
      continuum models for flow in the layer. The models of Elperin and Vikhansky
      [Europhys. Lett. 42, 619 (1998)] and Makse [Phys. Rev. Lett. 83, 3186 (1999)]
      show good agreement at low Fr while that of Khakhar et al. [Phys. Fluids, 9, 31
      (1997)] gives good predictions over the entire range of parameters considered. An
      analysis of the data indicate that the velocity gradient (gamma;) is nearly
      constant along the layer at low Fr, and the value calculated at the layer
      midpoint varies as gamma;(0)~[g sin(beta(0)-beta(s))/d cos beta(s)](1/2) for all
      the experimental data, where beta(s) is the static angle of repose and beta(0) is
      the interface angle at the layer midpoint. An extension of "heap" models (BCRE,
      BRdG) is used to predict the interface angle profiles, which are in reasonable
      agreement with experimental measurements.

PMID- 11580328
TI  - Velocity distributions and correlations in homogeneously heated granular media.
AB  - We compare the steady state velocity distributions from our three-dimensional
      inelastic hard sphere molecular dynamics simulation for homogeneously heated
      granular media, with the predictions of a mean field-type Enskog-Boltzmann
      equation for inelastic hard spheres [T. P. C. van Noije and M. H. Ernst, Granular
      Matter 1, 57 (1998)]. Although we find qualitative agreement for all values of
      density and inelasticity, the quantitative disagreement approaches approximately
      40% at high inelasticity or density. By contrast the predictions of the pseudo
      Maxwell molecule model [J. A. Carrillo, C. Cercignani, and I. M. Gamba, Phys.
      Rev. E, 62, 7700 (2000)] are both qualitatively and quantitatively different from
      those of our simulation. We also measure short-range and long-range velocity
      correlations exhibiting nonzero correlations at contact before the collision, and
      being consistent with a slow algebraic decay over a decade in the unit of the
      diameter of the particle, proportional to r(-(1+alpha)), where 0.2<alpha<0.3. The
      existence of these correlations implies the failure of the molecular chaos
      assumption and the mean field approximation, which is responsible for the
      quantitative disagreement of the inelastic hard sphere kinetic theory.

PMID- 11580329
TI  - Bifurcations of a driven granular system under gravity.
AB  - The molecular dynamics study on the granular bifurcation in a simple model is
      presented. The model consists of hard disks, which undergo inelastic collisions;
      the system is under the uniform external gravity and is driven by the heat bath.
      The competition between the two effects, namely, the gravitational force and the
      heat bath, is carefully studied. We found that the system shows three phases,
      namely, the condensed phase, the locally fluidized phase, and the granular
      turbulent phase, upon increasing the external control parameter. We conclude that
      the transition from the condensed phase to the locally fluidized phase is
      distinguished by the existence of fluidized holes, and the transition from the
      locally fluidized phase to the granular turbulent phase is understood by the
      destabilization transition of the fluidized holes due to mutual interference.

PMID- 11580330
TI  - Continuum saltation model for sand dunes.
AB  - We derive a phenomenological continuum saltation model for aeolian sand transport
      that can serve as an efficient tool for geomorphological applications. The
      coupled differential equations for the average density and velocity of sand in
      the saltation layer reproduce both the known equilibrium relations for the sand
      flux and the time evolution of the sand flux as predicted by microscopic
      saltation models. The three phenomenological parameters of the model are a
      reference height for the grain-air interaction, an effective restitution
      coefficient for the grain-bed interaction, and a multiplication factor
      characterizing the chain reaction caused by the impacts leading to a typical time
      or length scale of the saturation transients. We determine the values of these
      parameters by comparing our model with wind tunnel measurements. Our main
      interest are out of equilibrium situations where saturation transients are
      important, for instance at phase boundaries (ground/sand) or under unsteady wind
      conditions. We point out that saturation transients are indispensable for a
      proper description of sand flux over structured terrain, by applying the model to
      the windward side of an isolated dune, thereby resolving recently reported
      discrepancies between field measurements and theoretical predictions.

PMID- 11580331
TI  - Precollisional velocity correlations in a hard-disk fluid with dissipative
      collisions.
AB  - Velocity correlations are studied in granular fluids, modeled by the inelastic
      hard sphere gas. Making a density expansion of the Bogoliubov-Born-Green-Kirkwood
      Yvon hierarchy for the evolution of the reduced distributions, we predict the
      presence of precollisional velocity correlations. They are created by the
      propagation through correlated sequences of collisions (ring events) of the
      velocity correlations generated after dissipative collisions. The correlations
      have their origin in the dissipative character of collisions, being always
      present in granular fluids. The correlations, that manifest microscopically as an
      alignment of the velocities of a colliding pair produce modifications of
      collisional averages, in particular, the virial pressure. The pressure shows a
      reduction with respect to the elastic case as a consequence of the velocity
      alignment. Good qualitative agreement is obtained for the comparison of the
      numerical evaluations of the obtained analytical expressions and molecular
      dynamics results that showed evidence of precollisional velocity correlations [R.
      Soto and M. Mareschal, Phys. Rev. E 63, 041303 (2001)].

PMID- 11580332
TI  - Stick-slip fluctuations in granular drag.
AB  - We study fluctuations in the drag force experienced by an object moving through a
      granular medium. The successive formation and collapse of jammed states give a
      stick-slip nature to the fluctuations which are periodic at small depths but
      become "stepped" at large depths, a transition that we interpret as a consequence
      of the long-range nature of the force chains and the finite size of our
      experiment. Another important finding is that the mean force and the fluctuations
      appear to be independent of the properties of the contact surface between the
      grains and the dragged object. These results imply that the drag force originates
      in the bulk properties of the granular sample.

PMID- 11580333
TI  - Scaling laws in magneto-optical properties of aggregated ferrofluids.
AB  - Since statistically isotropic fractal aggregates of particles are a particular
      case of self-organized critical systems, we describe formally field-induced
      behaviors of aggregated ferrofluids as responses of regular at-equilibrium
      critical systems at the critical point to the small field conjugated to its order
      parameter. This leads us to expect some general scaling laws, which are checked
      numerically on two examples: the magnetic susceptibility and the magneto-optical
      linear dichroism of two-dimensional aggregated ferrofluids. This is performed by
      numerical simulations of such an aggregating system under weak magnetic field
      applied in the plane of the aggregates.

PMID- 11580334
TI  - Phase transition kinetics in colloid-polymer mixtures at triple coexistence:
      kinetic maps from free-energy landscapes.
AB  - We report a detailed experimental study of the kinetics of separation into
      coexisting gas, liquid, and crystal phases in a colloid-polymer mixture. Distinct
      kinetic regimes are identified, and interpreted in terms of the underlying "free
      energy landscape" of the system.

PMID- 11580335
TI  - Classification of ordering kinetics in three-phase systems.
AB  - Though equations of motion containing transport coefficients are required to
      quantitatively predict the phase-ordering dynamics of any given system, a great
      deal can be gleaned just from the shape of the free-energy landscape. We
      demonstrate how to extract the most information concerning phase-ordering
      phenomenology from a knowledge of a system's free-energy function, or phase
      diagram. Many putative pathways to equilibrium can be ruled out on the grounds of
      the second law of thermodynamics. In some parts of the phase diagram, these
      considerations are sufficient to completely determine the phase-ordering process
      without ever having to calculate a transport coefficient, even when three phases
      are present. The results include a large number of regions of the phase diagram
      with distinct phase-ordering kinetics, and some surprisingly elaborate routes to
      the equilibrium state. A process is found whereby a crystalline condensation
      nucleus becomes coated with a shell of gas, buffering it from a majority
      metastable liquid phase. Our results, based on thermodynamic arguments, are
      supported by numerical solution of model B, which describes diffusive phase
      ordering kinetics. Some of our predictions are tested against experimental
      observations of colloid-polymer mixtures, described in more detail in the
      preceding paper [F. Renth, W. C. K. Poon, and R. M. L. Evans, Phys. Rev. E 64,
      031402 (2001)]. A compact notation is developed to represent intricate phase
      ordering pathways.

PMID- 11580336
TI  - Field-induced structure transformation in electrorheological solids.
AB  - We have computed the local electric field in a body-centered tetragonal (bct)
      lattice of point dipoles via the Ewald-Kornfeld formulation, in an attempt to
      examine the effects of a structure transformation on the local-field strength.
      For the ground state of an electrorheological solid of hard spheres, we
      identified a different structure transformation from the bct to the face-centered
      cubic (fcc) lattices by changing the uniaxial lattice constant c under the hard
      sphere constraint. In contrast to the previous results, the local field exhibits
      a nonmonotonic transition from bct to fcc. As c increases from the bct ground
      state, the local field initially decreases rapidly towards the isotropic value at
      the body-centered cubic lattice, decreases further, reaching a minimum value and
      increases, passing through the isotropic value again at an intermediate lattice,
      reaches a maximum value and finally decreases to the fcc value. An experimental
      realization of the structure transformation is suggested. Moreover, the change in
      the local field can lead to a generalized Clausius-Mossotti equation for the bct
      lattices.

PMID- 11580337
TI  - Jamming creep of a frictional interface.
AB  - We measure the displacement response of a frictional multicontact interface
      between identical polymer glasses to a biased shear force oscillation. We
      evidence the existence, for maximum forces close below the nominal static
      threshold, of a jamming creep regime governed by an aging-rejuvenation
      competition acting within the micrometer-sized contacting asperities. The time
      dependence of the creep process deviates from the standard Rice-Ruina [J. R. Rice
      and A. L. Ruina, J. Appl. Mech. 50, 343 (1983)] phenomenology at early times;
      this suggests the possibility of an aging-rejuvenation competition at much
      smaller scales, within the nanometer-thick adhesive junctions.

PMID- 11580338
TI  - Apparent nonergodic behavior of supercooled liquids above the glass transition
      temperature.
AB  - A speckle pattern can be observed in the polarized component of light scattered
      from glass forming liquids far above their glass transition temperature. This
      speckle pattern fluctuates with characteristic time that corresponds to the
      relaxation time of the additional ultraslow component in the correlation function
      and is about seven orders of magnitude longer than the relaxation time of the
      alpha-process. This slow process is out of the experimental time window when the
      alpha-process is measured by means of the photon correlation spectroscopy and
      results in an apparent nonergodicity which can be seen as a baseline offset in
      the ensemble-averaged correlation function. In contrast, the time-averaged field
      correlation functions which have been measured in practically all light
      scattering studies always decay to zero. The slow process contributes a q
      dependent excess intensity to the polarized component of scattered light. The
      values of the nonergodicity parameters obtained from the static and dynamic light
      scattering experiments are equal. Both the slow component and the excess
      intensity result from denser regions of fractal character which develop in glass
      forming liquids on approaching the glass transition.

PMID- 11580339
TI  - Temporal fractal model for the anomalous dielectric relaxation of inhomogeneous
      media with chaotic structure.
AB  - The potential of the fractional derivative technique is demonstrated on the
      example of derivation of all three known patterns of anomalous, nonexponential
      dielectric relaxation of an inhomogeneous medium in the time domain. It is
      explicitly assumed that the fractional derivative is related to the
      dimensionality of a temporal fractal ensemble (in a sense that the relaxation
      times are distributed over a self-similar fractal system). The proposed fractal
      model of a microstructure of inhomogeneous media exhibiting nonexponential
      dielectric relaxation is built by singling out groups of hierarchically
      subordinated ensembles (subclusters, clusters, superclusters, etc.) from the
      entire statistical set available. Different relaxation functions are derived
      assuming that the real (physical) ensemble of relaxation times is confined
      between the upper and lower limits of self-similarity. It is predicted that at
      times, shorter than the relaxation time at the lowest (primitive) self-similarity
      level, the relaxation should be of a classical, Debye-like type, whatever the
      pattern of nonclassical relaxation at longer times.

PMID- 11580340
TI  - Viscoelasticity near the gel point: a molecular dynamics study.
AB  - We report on extensive molecular dynamics simulations on systems of soft spheres
      of functionality f, i.e., particles that are capable of bonding irreversibly with
      a maximum of f other particles. These bonds are randomly distributed throughout
      the system and imposed with probability p. At a critical concentration of bonds,
      p(c) approximately 0.2488 for f=6, a gel is formed and the shear viscosity eta
      diverges according to eta approximately (p(c)-p)(-s). We find s approximately 0.7
      in agreement with some experiments and with a recent theoretical prediction based
      on Rouse dynamics of phantom chains. The diffusion constant decreases as the gel
      point is approached but does not display a well-defined power law.

PMID- 11580341
TI  - Amorphous thin film growth: effects of density inhomogeneities.
AB  - A nonlinear stochastic growth equation for the spatiotemporal evolution of the
      surface morphology of amorphous thin films in the presence of potential density
      variations is derived from the relevant physical symmetries and compared to
      recent experimental results. Numerical simulations of the growth equation exhibit
      a saturation of the surface morphology for large film thickness originating from
      the inclusion of the density inhomogeneities. Furthermore, we argue why moundlike
      surface structures observed on vapor deposited amorphous films are not the result
      of the Grinfeld instability.

PMID- 11580342
TI  - Modes of counterion density fluctuations and counterion-mediated attractions
      between like-charged fluid membranes.
AB  - Counterion-mediated attractions between like-charged fluid membranes are long
      ranged and nonpairwise additive at high temperatures. At low temperatures,
      however, they are pairwise additive, and decay exponentially with the membrane
      separation. Using a simple model for the electrostatic attraction between like
      charged surfaces, we show that the nature of these attractions is determined by
      the dominant modes of fluctuations in the density of counterions. While the
      nonpairwise additive interactions arise from long-wavelength fluctuations and
      vanish at zero temperature, the short-ranged pairwise additive interactions arise
      from short-wavelength fluctuations and are stronger at low temperatures.

PMID- 11580343
TI  - Dissipation in dynamics of a moving contact line.
AB  - The dynamics of the deformations of a moving contact line is studied assuming two
      different dissipation mechanisms. It is shown that the characteristic relaxation
      time for a deformation of wavelength 2pi/|k| of a contact line moving with
      velocity v is given as tau(-1)(k)=c(v)|k|. The velocity dependence of c(v) is
      shown to depend drastically on the dissipation mechanism: we find c(v)=c(v=0)-2v
      for the case in which the dynamics is governed by microscopic jumps of single
      molecules at the tip (Blake mechanism), and c(v) approximately c(v=0)-4v when
      viscous hydrodynamic losses inside the moving liquid wedge dominate (de Gennes
      mechanism). We thus suggest that the debated dominant dissipation mechanism can
      be experimentally determined using relaxation measurements similar to the
      Ondarcuhu-Veyssie experiment [T. Ondarcuhu and M. Veyssie, Nature 352, 418
      (1991)].

PMID- 11580344
TI  - Film rupture in the diffuse interface model coupled to hydrodynamics.
AB  - The process of dewetting of a thin liquid film is usually described using a long
      wave approximation yielding a single evolution equation for the film thickness.
      This equation incorporates an additional pressure term-the disjoining pressure
      accounting for the molecular forces. Recently a disjoining pressure was derived
      coupling hydrodynamics to the diffuse interface model [L. M. Pismen and Y.
      Pomeau, Phys. Rev. E 62, 2480 (2000)]. Using the resulting evolution equation as
      a generic example for the evolution of unstable thin films, we examine the
      thickness ranges for linear instability and metastability for flat films, the
      families of stationary periodic and localized solutions, and their linear
      stability. The results are compared to simulations of the nonlinear time
      evolution. From this we conclude that, within the linearly unstable thickness
      range, there exists a well defined subrange where finite perturbations are
      crucial for the time evolution and the resulting structures. In the remainder of
      the linearly unstable thickness range the resulting structures are controlled by
      the fastest flat film mode assumed up to now for the entire linearly unstable
      thickness range. Finally, the implications for other forms of disjoining pressure
      in dewetting and for spinodal decomposition are discussed.

PMID- 11580345
TI  - Dynamics of capillary spreading along hydrophilic microstripes.
AB  - We have studied the capillary spreading of a Newtonian liquid along hydrophilic
      microstripes that are chemically defined on a hydrophobic substrate. The front of
      the spreading film advances in time according to a power law x=Bt(1/2). This
      exponent of 1/2 is much larger than the value 1/10 observed in the axisymmetric
      spreading of a wetting droplet. It is identical to the exponent found for wicking
      in open or closed microchannels. Even though no wicking occurs in our system, the
      influence of surface curvature induced by the lateral confinement of the liquid
      stripe also leads to an exponent of 1/2 but with a strongly modified prefactor B.
      We obtain excellent experimental agreement with the predicted time dependence of
      the front location and the dependence of the front speed on the stripe width.
      Additional experiments and simulations reveal the influence of the reservoir
      volume, liquid material parameters, edge roughness, and nonwetting defects. These
      results are relevant to liquid dosing applications or microfluidic delivery
      systems based on free-surface flow.

PMID- 11580346
TI  - Porous silicon formation and electropolishing.
AB  - Electrochemical etching of silicon in hydrofluoride containing electrolytes leads
      to pore formation for low and to electropolishing for high applied current. The
      transition between pore formation and polishing is accompanied by a change of the
      valence of the electrochemical dissolution reaction. The local etching rate at
      the interface between the semiconductor and the electrolyte is determined by the
      local current density. We model the transport of reactants and reaction products
      and thus the current density in both, the semiconductor and the electrolyte.
      Basic features of the chemical reaction at the interface are summarized in the
      law of mass-action-type boundary conditions for the transport equations at the
      interface. We investigate the linear stability of a planar and flat interface.
      Upon increasing the current density the stability flips either through a change
      of the valence of the dissolution reaction or by a nonlinear boundary condition
      at the interface.

PMID- 11580347
TI  - Nonsingular self-preserving regimes of coagulation-condensation process.
AB  - Growth of disperse particles is considered assuming that the preexisting disperse
      particles coagulate and grow simultaneously by condensing a low volatile
      substance (vapor, in what follows) whose concentration is permanently refreshed
      by a spatially uniform and constant in time source. The kinetics of the
      condensation-coagulation process is studied under the assumption that the
      condensation rate and coagulation kernels are homogeneous functions of the
      particle masses. The power exponents characterizing these functions define the
      asymptotic self-preserving regimes of the particle growth. Four such regimes are
      detected: (i) the mass of the disperse phase consumes all vapor and grows
      linearly with time, while the vapor concentration grows (or even drops) with time
      as its power s<1; (ii) the mass of the disperse phase grows slower than a linear
      function of time, while the vapor concentration grows asymptotically as time;
      (iii) the mass of disperse phase remains finite; and (iv) both, the mass of
      disperse phase and the vapor concentration grow linearly with time. For all above
      regimes the equations are derived defining the shape of the asymptotic mass
      distribution. The latter is shown to depend on a combination of the particle mass
      and time. The theory is illustrated by two exactly soluble models, and numerical
      results for the condensation-coagulation growth of aerosol particles in free
      molecular regime.

PMID- 11580348
TI  - Reconstructed rough growing interfaces: ridge-line trapping of domain walls.
AB  - We investigate whether surface reconstruction order exists in stationary growing
      states at all length scales or only below a crossover length l(rec). The latter
      behavior would be similar to surface roughness in growing crystal surfaces; below
      the equilibrium roughening temperature they evolve in a layer-by-layer mode
      within a crossover length scale l(R), but are always rough at large length
      scales. We investigate this issue in the context of Kardar-Parisi-Zhang (KPZ)
      type dynamics and a checkerboard type reconstruction, using the restricted solid
      on-solid model with negative monatomic step energies. This is a topology where
      surface reconstruction order is compatible with surface roughness and where a so
      called reconstructed rough phase exists in equilibrium. We find that during
      growth reconstruction order is absent in the thermodynamic limit, but exists
      below a crossover length l(rec)>l(R), and that this local order fluctuates
      critically. Domain walls become trapped at the ridge lines of the rough surface,
      and thus the reconstruction order fluctuations are slaved to the KPZ dynamics.

PMID- 11580349
TI  - Dielectric and elastic properties of liquid crystals.
AB  - The structural properties, the static and relaxation dielectric coefficients
      [epsilon(j) and epsilon(j)(omega) (j= ||, perpendicular)], the rotational
      diffusion constants D( perpendicular) and D( ||), the orientational correlation
      times tau(1)(i0) (i=0,1), and the bulk elastic constants K(i) (i=1,2,3) are
      investigated for polar liquid crystals, such as 4-n-pentyl-4(')-cyanobiphenyl
      (5CB). epsilon(j) are calculated by a combination of the existing molecular
      theory and statistical-mechanical approach (SMA) that takes into account
      translational and orientational correlations as well as their coupling, whereas
      epsilon(j)(omega) are calculated by combining SMA and nuclear magnetic resonance
      relaxation theory, both based on a rotational diffusion model in which the
      reorientation of an individual molecule is assumed as stochastic Brownian motion
      in a potential of mean torque. Reasonable agreement between the calculated and
      experimental values of epsilon(j) and epsilon(j)(omega) for 5CB is obtained. The
      bulk Frank elastic constants K(i) (i=1,2,3), for splay, twist, and bend
      distortion modes, as well as their ratios K(3)/K(1) and K(2)/K(1) are also
      obtained.

PMID- 11580350
TI  - Pretransitional optical activity of short-pitched chiral nematic liquid crystals.
AB  - We have developed, using the de Gennes theory of short-range orientational order
      in the isotropic phase, a closed-form expression for the temperature dependence
      of the pretransitional optical activity of chiral nematics. Detailed calculations
      are included and the results are expressed in a form that can be easily tested
      experimentally. The theoretical predictions are supported by experimental data.

PMID- 11580351
TI  - Dynamics of side-chain liquid-crystalline polymers: a dielectric spectroscopy
      investigation.
AB  - We have studied the dynamics in two side-chain liquid-crystalline derivatives of
      poly(norbornene diethylester) with dielectric spectroscopy within the temperature
      range 190-433 K and the pressure range 1-3000 bars. Optical microscopy, x-ray
      scattering, and differential scanning calorimetry (DSC) revealed the formation of
      a nematic- and a smectic-A phase, respectively, in the polymers with the shorter
      and longer spacers. Multiple relaxation processes exist originating from the
      backbone and mesogenic dipoles. In the smectic-A phase two relaxation processes
      exist above the DSC glass temperature (alpha and alpha(')) which merge with
      decreasing temperature or with increasing pressure, thus suggesting a common
      molecular mechanism. The faster process is the segmental (alpha) relaxation
      associated with the dynamic glass transition, whereas the slower process reflects
      mainly the side-chain dynamics within the smectic layers. Pressure was found to
      increase the glass temperature in the nematic and smectic phases and the dT(g)/dP
      was 18.7 and 16.9 K/kbar, respectively. However, the effect of pressure in
      inducing the isotropic-to-smectic transition is more drastic as dT(SI)/dP=26.4
      K/kbar.

PMID- 11580352
TI  - Polarized infrared spectroscopic study on the orientation of the molecules in the
      smectic-C* phase of a ferroelectric liquid crystal with a naphthalene ring:
      alternative theory for the analysis of polarization-angle-dependent intensity
      changes.
AB  - A theory to explain the polarization-angle dependence of polarized infrared
      spectra of a ferroelectric liquid crystal in the surface-stabilized ferroelectric
      liquid crystal state is proposed. It describes the relationship between the
      intensity of the absorption bands and the polarization angle of the infrared
      radiation. Using this theory the polarization-angle dependence of the infrared
      band intensities was analyzed for a ferroelectric liquid crystal with a
      naphthalene ring and two phenyl rings with a stacked layer structure in the
      smectic-C* phase. The polarization-angle-dependent spectra were measured at 137
      degrees C under external dc electric fields of +40 and -40 V to investigate the
      orientation of the molecules. Plots of the infrared absorbance versus
      polarization angle for representative bands were subjected to a curve fitting
      procedure by a least squares method. From the curves obtained the orientation of
      the transition dipole moments with respect to the molecular long axis and the
      orientation of the molecular long axis with respect to the rubbing direction of
      the cell were estimated based upon the suggested theory. The polarization-angle
      dependent infrared spectra obtained were also analyzed by two-dimensional (2D)
      correlation spectroscopy. The 2D correlation analysis clearly detects a slight
      phase difference in the polarization-angle dependence which is hardly recognized
      in ordinary plots of the intensity changes in the infrared bands. The 2D
      correlation analysis allows us to separate asymmetric and symmetric stretching
      bands due to the chiral methyl group from those arising from other methyl groups
      in the alkyl chains.

PMID- 11580353
TI  - Dynamics of dissipative ordered fluids.
AB  - A variational principle is proposed that allows to derive the equations of motion
      for a fluid with a general microstructure described by a tensorial order
      parameter. The only constitutive ingredients are the densities of the free energy
      and the dissipation, both subject to appropriate invariance requirements. As an
      illustration, it is shown how the hydrodynamic theory for uniaxial nematic liquid
      crystals can be derived within this setting.

PMID- 11580354
TI  - Biaxial model of the surface anchoring of bent-core smectic liquid crystals.
AB  - In synclinically tilted smectic phases, bent-core liquid crystal molecules
      aligned with the director in the plane of a cell boundary will, in general, have
      their molecular (bow) planes parallel to the boundary, normal to it, or at a well
      defined intermediate orientation. A model describing the interaction of such bent
      core (banana-shaped) molecules with planar surfaces that distinguishes
      energetically between molecules lying flat on the surface and those oriented edge
      on is given by a biaxial modification of the uniaxial surface anchoring
      expression used for chiral smectics of rod-shaped molecules. When combined with a
      field-induced straightening of the smectic layers, the model provides a mechanism
      for the transition from an analog to a bistable director response observed
      electro-optically in the ferroelectric banana-shaped material (R,S)-MHOBOW.

PMID- 11580355
TI  - Separate measurements of the flexoelectric and surface polarization in a model
      nematic liquid crystal p-methoxybenzylidene-p'-butylaniline: validity of the
      quadrupolar approach.
AB  - The temperature dependences of the surface polarization have been measured at the
      interface of a conductive glass with both the homogeneously and homeotropically
      oriented nematic liquid crystal p-methoxybenzylidene-p(')-butylaniline. The
      polarization was found in the field-off regime from the pyroelectric response of
      a cell to a short laser pulse, absorbed in the bulk of the liquid crystal. The
      temperature increment was calculated from the measurements of the birefringence
      induced by the same light pulse. It has been shown that the surface polarization
      at the homeotropic (m(h)) and planar (m(p)) interfaces is directed from an
      interface into the bulk and from the bulk to an interface, respectively (with a
      magnitude m(h) approximately -0.3 pC/m and m(p) approximately +0.2 pC/m at 25
      degrees C). The experimental data may be explained in terms of the quadrupole
      model of the order-electric polarization with account of some additional
      contribution from molecular dipoles. The same technique also allows for the
      measurements of the z component of the flexoelectric polarization using a
      pyroelectric response of a hybrid (homeoplanar) aligned nematic cell and proper
      subtracting of the surface contributions. The flexoelectric polarization has been
      shown to be opposite to the sum of the surface terms m(h)+m(p) and directed from
      the planar to homeotropic interface. This means that the sum of the flexoelectric
      coefficients e=(e(1)+e(3)) is positive (e congruent with 1.7 pC/m at 28 degrees
      C). The temperature dependence of e has been shown to involve a combination of
      both the quadrupolar and dipolar contributions.

PMID- 11580356
TI  - Surface freezing in n-alkane solutions: the relation to bulk phases.
AB  - Surface freezing (SF) was investigated in tricosane-dodecane alkane solutions as
      a function of temperature (T) and molar concentration of tricosane (phi), using
      surface tension and synchrotron x-ray surface diffraction techniques. A
      crystalline SF monolayer, having a rotator R(II) structure, was found to exist
      for 35 degrees C</=T</=50 degrees C and 0.3</=phi</=1. The extended temperature
      range allowed to determine the linear-expansion coefficient of the SF monolayer,
      (dd/dT)/d=6.5 x 10(-4) degrees C-1. A simple thermodynamical model based on the
      theory of ideal solutions is shown to account well for the phi dependence of the
      SF temperature T(s)(phi). The study shows that the temperature range of existence
      of the surface frozen layer at each phi, the phi range over which SF is observed,
      and the bulk solidification behavior, are intimately related. All are determined
      by the rotator-liquid dissolution line T(dR)(phi).

PMID- 11580357
TI  - Uniform and nonuniform textures of a nematic liquid crystal in contact with an
      inhomogeneous substrate.
AB  - A semi-infinite sample of a nematic liquid crystal in contact with a flat solid
      substrate, possessing an alternating stripe pattern of planar and homeotropic
      anchoring, is studied in the framework of the Frank-Oseen model. The case of
      strong anchoring on one of the stripes is treated by means of bifurcation
      analysis, whereas the case of weak anchoring is studied by means of numerical
      minimization of the free energy functional. We find a second order phase
      transition between the uniform homeotropic or planar alignment and a distorted
      director configuration. The effect of the stripe width and the anchoring strength
      on the location of this transition and on the bulk orientation of the nematic
      director is also studied.

PMID- 11580359
TI  - Stokes drag of spherical particles in a nematic environment at low Ericksen
      numbers.
AB  - As a first approach to the motion of particles in anisotropic liquids, we study
      the Stokes drag of spherical particles in three different nematic environments: a
      uniform director field, the Saturn-ring configuration, and the dipole
      configuration. Two independent friction coefficients for the respective motion
      parallel and perpendicular to the overall symmetry axis exist. We determine these
      coefficients by solving the Ericksen-Leslie equations for low Ericksen numbers,
      i.e., when the director field is not influenced by the flow of the liquid crystal
      around the particle. We present streamline patterns and interpret them. Compared
      to the uniform director field and the Saturn-ring configuration, the dipolar
      configuration lacks a mirror plane as a symmetry element whose consequences we
      illustrate.

PMID- 11580358
TI  - Disclination loop behavior near the nematic-isotropic transition.
AB  - We investigate the behavior of disclination loops in the vicinity of the first
      order nematic-isotropic transition in the Lebwohl-Lasher and related models. We
      find that two independent measures of the transition temperature, the free
      energy, and the distribution of disclination line segments, give essentially
      identical values. We also calculate the distribution function D(p) of
      disclination loops of perimeter p and fit it to a quasiexponential form. Below
      the transition, D(p) falls off exponentially, while in the neighborhood of the
      transition, it decays with a power-law exponent approximately equal to 2.5,
      consistent with a "blowout" of loops at the transition. In a modified Lebwohl
      Lasher model with a strongly first-order transition we are able to measure a jump
      in the disclination line tension at the transition, which is too small to be
      measured in the Lebwohl-Lasher model. We also measure the monopole charge of the
      disclination loops and find that in both the original and modified Lebwohl-Lasher
      models, there are large loops that carry monopole charge, while smaller isolated
      loops do not. Overall, the nature of the topological defects in both models is
      very similar.

PMID- 11580360
TI  - Ideal trefoil knot.
AB  - A set of self-contact points of the most tight, parametrically tied trefoil knot
      is determined. The knot is subjected to further tightening procedure based on the
      shrink-on-no-overlaps algorithm. Changes in the structure of the set of the self
      contact points are monitored and the final form of the set is determined.

PMID- 11580362
TI  - Delayed luminescence of biological systems arising from correlated many-soliton
      states.
AB  - The kinetics of the delayed luminescence arising from correlated coherent many
      soliton states in low-dimensional macromolecular systems, is calculated and shown
      to be different from the one arising from independent soliton states. The
      correlation between coherent electron states is essential at relatively high
      levels of excitation in the presence of very long macromolecules in a system.
      These conditions can be fulfilled in such biological systems, like algae
      Acetabularia Acetabulum. The cytoskeleton of this unicellular alga contains
      macromolecular structures (actin filaments, microtubules, etc.) of the length of
      several hundreds angstroms and more, in which many-soliton coherent states can
      exist. Indeed, the correlated coherent model is shown to give better fit of the
      experimental data for this type of algae in a wide range of intensities of the
      stimulating light, as compared with the model of noncorrelated solitons. The
      nonlinearity of the dependence of delayed luminescence intensity on the level of
      excitation increases with the increase of correlation between solitons.

PMID- 11580361
TI  - Phase diagram of force-induced DNA unzipping in exactly solvable models.
AB  - The mechanical separation of a double helical DNA structure induced by forces
      pulling apart the two DNA strands ("unzipping") has been the subject of recent
      experiments. Analytical results are obtained within various models of interacting
      pairs of directed walks in the (1,1,ellipsis,1) direction on the hypercubic
      lattice, and the phase diagram in the force-temperature plane is studied for a
      variety of cases. The scaling behavior is determined at both the unzipping and
      melting transitions. We confirm the existence of a cold denaturation transition
      recently observed in numerical simulations: for a finite range of forces, the
      system is unzipped by decreasing the temperature. The existence of this
      transition is rigorously established for generic lattice and continuum space
      models.

PMID- 11580363
TI  - Measure representation and multifractal analysis of complete genomes.
AB  - This paper introduces the notion of measure representation of DNA sequences.
      Spectral analysis and multifractal analysis are then performed on the measure
      representations of a large number of complete genomes. The main aim of this paper
      is to discuss the multifractal property of the measure representation and the
      classification of bacteria. From the measure representations and the values of
      the D(q) spectra and related C(q) curves, it is concluded that these complete
      genomes are not random sequences. In fact, spectral analyses performed indicate
      that these measure representations, considered as time series, exhibit strong
      long-range correlation. Here the long-range correlation is for the K-strings with
      dictionary ordering, and it is different from the base pair correlations
      introduced by other people. For substrings with length K=8, the D(q) spectra of
      all organisms studied are multifractal-like and sufficiently smooth for the C(q)
      curves to be meaningful. With the decreasing value of K, the multifractality
      lessens. The C(q) curves of all bacteria resemble a classical phase transition at
      a critical point. But the "analogous" phase transitions of chromosomes of
      nonbacteria organisms are different. Apart from chromosome 1 of C. elegans, they
      exhibit the shape of double-peaked specific heat function. A classification of
      genomes of bacteria by assigning to each sequence a point in two-dimensional
      space (D(-1),D1) and in three-dimensional space (D(-1),D1,D(-2)) was given.
      Bacteria that are close phylogenetically are almost close in the spaces (D(
      1),D1) and (D(-1),D1,D(-2)).

PMID- 11580364
TI  - Fluctuation-induced memory retrieval in a pulsed neural network storing sparse
      patterns with hierarchical correlations.
AB  - An associative memory in a pulsed neural network composed of the FitzHugh-Nagumo
      models storing sparse patterns with hierarchical correlations is investigated.
      The memory patterns composed of 0/1 digits are represented by the synchronous
      periodic firings of the neurons. It is found that the target pattern and the OR
      pattern are retrieved individually by controlling the intensity of fluctuations
      in the system.

PMID- 11580365
TI  - Coherence resonance with multiple peaks in a coupled FitzHugh-Nagumo model.
AB  - Coherence resonance in a coupled excitable system is studied, through both a
      computer simulation and a circuit experiment, using a piecewise linear version of
      the FitzHugh-Nagumo model. White noise is added to the first element and spikes
      are accordingly generated and transmitted to the second element. The mean,
      standard deviation, and coefficient of variation of the interspike intervals in
      the second element have multiple peaks as the noise strengthens, when the
      coupling strength is small. This results from the phase locking to the spikes
      that the noise generates.

PMID- 11580368
TI  - Theoretical analysis of array-enhanced stochastic resonance in the diffusively
      coupled FitzHugh-Nagumo equation.
AB  - The array-enhanced stochastic resonance (AESR) in the diffusively coupled
      FitzHugh-Nagumo equation is investigated. The two properties of AESR, namely, the
      scaling of the optimal noise intensity and the enhancement of the maximum value
      of the correlation coefficient as a function of the coupling strength, are
      analyzed theoretically. By transforming the dynamics of N elements into that of
      the mean and the deviation from it, it is found that AESR is caused by the
      correlation between them. A low-dimensional model that reproduces the above
      properties is constructed.

PMID- 11580366
TI  - Noise breaking the twofold symmetry of photosynthetic reaction centers: electron
      transfer.
AB  - In this work we present a stochastic model to elucidate the unidirectionality of
      the primary charge separation process in the bacterial reaction centers where two
      symmetric ways of electron transfer (ET), starting from the common electron
      donor, are possible. We have used a model of three sites/molecules with ET
      beginning at site 1 with the option to proceed to site 2 or site 3. If the direct
      ET between sites 2 and 3 is not allowed and electron cannot escape from the
      system then it is shown that the different stochastic fluctuations in the energy
      of sites and the interaction between sites on these two ways are sufficient to
      cause the transient asymmetric electron distribution at site 2 and 3 during
      relaxation to the steady state. This means that overall asymmetric ET can be
      caused by the transient asymmetric electron distribution if there is a
      possibility for an electron to escape from the three-site system. To explore this
      possibility we have introduced a sink into the model at the end of each of the
      sites 2 and 3. The dependence of the asymmetry in electron transfer on the value
      of the sink parameter, introduced through an additional imaginary diagonal matrix
      element of the Hamiltonian, was investigated. Results show indeed that the
      unidirectionality of the electron transfer generated in the system of three
      molecules depends strongly on the sink parameter value.

PMID- 11580367
TI  - Statistical mechanics of learning with soft margin classifiers.
AB  - We study the typical learning properties of the recently introduced soft margin
      classifiers (SMCs), learning realizable and unrealizable tasks, with the tools of
      statistical mechanics. We derive analytically the behavior of the learning curves
      in the regime of very large training sets. We obtain exponential and power laws
      for the decay of the generalization error towards the asymptotic value, depending
      on the task and on general characteristics of the distribution of stabilities of
      the patterns to be learned. The optimal learning curves of the SMCs, which give
      the minimal generalization error, are obtained by tuning the coefficient
      controlling the trade-off between the error and the regularization terms in the
      cost function. If the task is realizable by the SMC, the optimal performance is
      better than that of a hard margin support vector machine and is very close to
      that of a Bayesian classifier.

PMID- 11580369
TI  - Random energy model in nonextensive statistical mechanics.
AB  - Free energy for random energy model is obtained for different values of parameter
      q defined in nonextensive statistical mechanics. System is found either in
      paramagnetic or spin-glass phases depending on the value of q.

PMID- 11580370
TI  - Inherent-structure dynamics and diffusion in liquids.
AB  - The self-diffusion constant D is expressed in terms of transitions among the
      local minima (inherent structures, IS) of the N-body potential-energy surface or
      landscape, and their correlations. The formulas are evaluated and tested against
      simulation in the supercooled, unit-density Lennard-Jones liquid. The
      approximation of uncorrelated IS-transition (IST) vectors D0, greatly exceeds D
      for the highest T, but merges with simulation at reduced T approximately 0.50,
      close to the estimated mode-coupling temperature T(c). Since uncorrelated IST's
      are associated with a hopping mechanism, the condition D approximately D0
      provides a new way to identify the crossover to hopping. The results suggest that
      theories of diffusion in deeply supercooled liquids may be based on weakly
      correlated IST's.

PMID- 11580371
TI  - Collective dynamics in liquid lead. II. Mode contributions to time correlation
      functions.
AB  - Mode contributions of different collective excitations to the density-density
      time correlation function in liquid lead are studied within the nine-variable
      approach of generalized collective modes. It is shown, that a kinetic relaxing
      mode, caused by slow density fluctuations, defines almost completely the shape of
      density-density time correlation function for wave numbers close to the main peak
      position of the static structure factor. The physical meaning of this mode is
      discussed.

PMID- 11580372
TI  - Nonlinear effects in the stability of highly charged colloidal suspensions.
AB  - We investigate the nonlinear effects related to the formation of particle
      counterion clusters in highly charged asymmetric colloidal suspensions. The
      ocurrence of such clustering is experimentally probed by studying the stability
      of the colloidal system. The results demonstrate that a renormalized charge is
      needed in order to explain the observed critical coagulation concentrations. This
      renormalization is predicted by an extension of the Debye-Huckel-Bjerrum liquid
      state theory [A. Diehl, M. C. Barbosa, and Y. Levin, Europhys. Lett. 53, 86
      (2001)]. Therefore, counterion condensation seems to become apparent in particle
      aggregation processes through control of the repulsive barrier that keeps the
      system stable. As a consequence of the agreement, new insights into the
      microscopic state of highly charged complex fluids follow.

PMID- 11580374
TI  - Extremal properties of random trees.
AB  - We investigate extremal statistical properties such as the maximal and the
      minimal heights of randomly generated binary trees. By analyzing the master
      evolution equations we show that the cumulative distribution of extremal heights
      approaches a traveling wave form. The wave front in the minimal case is governed
      by the small-extremal-height tail of the distribution, and conversely, the front
      in the maximal case is governed by the large-extremal-height tail of the
      distribution. We determine several statistical characteristics of the extremal
      height distribution analytically. In particular, the expected minimal and maximal
      heights grow logarithmically with the tree size, N, h(min) approximately v(min)
      ln N, and h(max) approximately v(max) ln N, with v(min)=0.373365ellipsis and
      v(max)=4.31107ellipsis, respectively. Corrections to this asymptotic behavior are
      of order O(ln ln N).

PMID- 11580375
TI  - Noise-enhanced stability of periodically driven metastable states.
AB  - We study the effect of noise-enhanced stability of periodically driven metastable
      states in a system described by piecewise linear potential. We find that the
      growing of the average escape time with the intensity of the noise is depending
      on the initial condition of the system. We analytically obtain the condition for
      the noise enhanced stability effect and verify it by numerical simulations.

PMID- 11580373
TI  - Blowout bifurcation with non-normal parameters in population dynamics.
AB  - Interesting dynamic behaviors have been associated with the transverse stability
      of an invariant subspace (e.g., riddled basins or on-off intermittency).
      Recently, these complex behaviors have been generalized to cases of models with
      non-normal parameters showing that these behaviors might be widespread. In this
      Brief Report I demonstrate this type of complex dynamics in models of interacting
      populations for which the invariant subspace is defined by species extinction. In
      the context of the current biodiversity crisis, implications of these behaviors
      for population biology are discussed.

PMID- 11580376
TI  - Universal relations in the finite-size correction terms of two-dimensional Ising
      models.
AB  - Quite recently, Izmailian and Hu [Phys. Rev. Lett. 86, 5160 (2001)] studied the
      finite-size correction terms for the free energy per spin and the inverse
      correlation length of the critical two-dimensional Ising model. They obtained the
      universal amplitude ratio for the coefficients of two series. In this study we
      give a simple derivation of this universal relation; we do not use an explicit
      form of series expansion. Moreover, we show that the Izmailian and Hu's relation
      is reduced to a simple and exact relation between the free energy and the
      correlation length. This equation holds at any temperature and has the same form
      as the finite-size scaling.

PMID- 11580377
TI  - World Wide Web scaling exponent from Simon's 1955 model.
AB  - The statistical properties of the World Wide Web have attracted considerable
      attention recently since self-similar regimes were first observed in the scaling
      of its link structure. One characteristic quantity is the number of (in-)links k
      that point to a particular web page. Its probability distribution P(k) shows a
      pronounced power-law scaling P(k) approximately k(-gamma) that is not readily
      explained by standard random graph theory. Here, we recall a simple and elegant
      model for scaling phenomena in general copy- and growth-processes as proposed by
      Simon in 1955. When combined with an experimental measurement of network growth
      in the World Wide Web, this classical model is able to model the in-link dynamics
      and predicts the scaling exponent gamma=2.1 in accordance with observation.

PMID- 11580378
TI  - Growing dynamics of Internet providers.
AB  - In this paper we present a model for the growth and evolution of Internet
      providers. The model reproduces the data observed for the Internet connection as
      probed by tracing routes from different computers. This problem represents a
      paramount case of study for growth processes in general, but can also help in the
      understanding the properties of the Internet. Our main result is that this
      network can be reproduced by a self-organized interaction between users and
      providers that can rearrange in time. This model can then be considered as a
      prototype model for the class of phenomena of aggregation processes in social
      networks.

PMID- 11580379
TI  - Quantifying and interpreting collective behavior in financial markets.
AB  - Firms having similar business activities are correlated. We analyze two different
      cross-correlation matrices C constructed from (i) 30-min price fluctuations of
      1000 US stocks for the two-year period 1994-95 and (ii) one-day price
      fluctuations of 422 US stocks for the 35-year period 1962-96. We find that the
      eigenvectors of C corresponding to the largest eigenvalues allow us to partition
      the set of all stocks into distinct subsets. These subsets are similar to
      business sectors, and are stable for extended periods of time. We find that price
      fluctuations of these subsets are characterized by power-law decaying time
      correlations, reminiscent of strongly interacting systems.

PMID- 11580381
TI  - Divergence measure between chaotic attractors.
AB  - We propose a measure of divergence of probability distributions for quantifying
      the dissimilarity of two chaotic attractors. This measure is defined in terms of
      a generalized entropy. We illustrate our procedure by considering the effect of
      additive noise in the well known Henon attractor. Finally, we show how our
      approach allows one to detect nonstationary events in a time series.

PMID- 11580380
TI  - Spiral wave dynamics under feedback derived from a confined circular domain.
AB  - Spiral waves are induced in a thin layer of the light-sensitive Belousov
      Zhabotinsky reaction and controlled by a time-dependent uniform illumination. The
      intensity of the illumination is taken to be proportional to the average wave
      activity observed within a circular domain of the reaction layer. Stabilization
      and destabilization of spiral waves, as well as the existence of additional types
      of attractors, are demonstrated. A simple mathematical description is proposed in
      order to explain the existence of the attractors and the dependence of their size
      on the time delay in the feedback loop.

PMID- 11580382
TI  - Intermittency of a passive tracer in the inverse energy cascade.
AB  - We report an experimental study of the dispersion of a passive tracer in the two
      dimensional inverse energy cascade, which shows that a nonintermittent velocity
      field can sustain a strongly intermittent concentration field. The experiment
      suggests the exponents of the intermittent concentration field saturate at large
      orders towards xi(infinity) approximately 1.2. These observations are in
      excellent agreement with a recent numerical work [A. Celani, A. Lanotte, A.
      Mazzino, and M. Vergassola, Phys. Rev. Lett. 84, 2385 (2000)] and theoretical
      expectations [E. Balkovsky and V. Lebedev, Phys. Rev. E 58, 5776 (1998); V.
      Yakhot, ibid. 55, 329 (1997)].

PMID- 11580383
TI  - Prior mapping for nonlinear flows in random environments.
AB  - We analyze nonlinear flows in randomly heterogeneous environments, which are
      characterized by state-dependent diffusion coefficients with spatially correlated
      structures. The prior Kirchhoff mapping is used to describe such systems by
      linear stochastic partial differential equations with multiplicative noise. These
      are solved through moment equations which are closed, alternatively, either by
      perturbation expansions, or by a posterior linear mapping closure. The latter
      relies on the assumption that the state variable is a spatially distributed
      Gaussian field. We demonstrate that the former approach is more robust.

PMID- 11580385
TI  - Oscillations in a chain of rod-shaped colloidal particles in a plasma.
AB  - Oscillations in the one-dimensional chain consisting of rotatorlike particles
      levitating in a plasma are studied. General equations of motion for such a chain
      are derived. It is demonstrated that new oscillation modes associated with the
      rotational degrees of freedom appear for such a configuration. The dispersion
      characteristics of the modes are analyzed. Collective oscillations and
      equilibrium in lattices composed of cylindrical particles in a plasma are
      discussed.

PMID- 11580384
TI  - Results on the energy-relaxation rates of dense two-temperature aluminum, carbon,
      and silicon plasmas close to liquid-metal conditions.
AB  - We present results for the electron-ion energy relaxation coupling constants
      g(ei)(T(e),T(i),kappa) for aluminum, carbon, and silicon plasmas at several
      electron and ion temperatures T(i), T(e) of experimental interest. The
      calculations use the Fermi golden rule and the Landau-Spitzer model valid at weak
      electron-ion coupling, as well as the coupled-mode approach suitable for strong
      coupling. A physically motivated simple derivation of the coupled-mode energy
      relaxation formula for two-component charged fluids is presented. While the
      commonly used weak-coupling theories predict relaxation constants relatively
      independent of the ion temperature, the strong-coupling theory predicts energy
      relaxation constants that become smaller by an order of magnitude as the ion
      temperature is lowered.

PMID- 11580386
TI  - Inverse scattering for the diffusion equation with general boundary conditions.
AB  - We consider the inverse scattering problem for the diffusion equation. A solution
      to this problem in the form of an explicit inversion formula is derived. Computer
      simulations are used illustrate our approach in model systems.

PMID- 11580387
TI  - On-ramp simulations and solitary waves of a car-following model.
AB  - An on-ramp simulation of a car-following model reveals qualitatively similar
      results to previous simulations of continuum models carried out by Helbing et al.
      [Phys. Rev. Lett. 82, 4360 (1999)] and by Lee, Lee, and Kim[Phys. Rev. E 59, 5101
      (1999)]. Here, we discuss the solitary solution type in greater detail. It can be
      approximated by a Kortweg-de Vries equation derived from the analogous continuum
      version. Hence, this establishes a further link between these two traffic
      simulation types and supports the idea that models of either kind lead to similar
      results when they contain a relaxation term.

PMID- 11580388
TI  - Kinetic roughening in slow combustion of paper.
AB  - Results of experiments on the dynamics and kinetic roughening of one-dimensional
      slow-combustion fronts in three grades of paper are reported. Extensive averaging
      of the data allows a detailed analysis of the spatial and temporal development of
      the interface fluctuations. The asymptotic scaling properties, on long length and
      time scales, are well described by the Kardar-Parisi-Zhang (KPZ) equation with
      short-range, uncorrelated noise. To obtain a more detailed picture of the strong
      coupling fixed point, characteristic of the KPZ universality class, universal
      amplitude ratios, and the universal coupling constant are computed from the data
      and found to be in good agreement with theory. Below the spatial and temporal
      scales at which a crossover takes place to the standard KPZ behavior, the fronts
      display higher apparent exponents and apparent multiscaling. In this regime the
      interface velocities are spatially and temporally correlated, and the
      distribution of the magnitudes of the effective noise has a power-law tail. The
      relation of the observed short-range behavior and the noise as determined from
      the local velocity fluctuations is discussed.

PMID- 11580390
TI  - Exact tagged particle correlations in the random average process.
AB  - We study analytically the correlations between the positions of tagged particles
      in the random average process, an interacting particle system in one dimension.
      We show that in the steady state, the mean-squared autofluctuation of a tracer
      particle grows subdiffusively sigma(2)0(t) approximately t(1/2) for large time t
      in the absence of external bias but grows diffusively sigma(2)0(t) approximately
      t in the presence of a nonzero bias. The prefactors of the subdiffusive and
      diffusive growths, as well as the universal scaling function describing the
      crossover between them, are computed exactly. We also compute sigma(2)(r)(t), the
      mean-squared fluctuation in the position difference of two tagged particles
      separated by a fixed tag shift r in the steady state and show that the external
      bias has a dramatic effect on the time dependence of sigma(2)(r)(t). For fixed
      r,sigma(2)(r)(t) increases monotonically with t in the absence of bias, but has a
      nonmonotonic dependence on t in the presence of bias. Similarities and
      differences with the simple exclusion process are also discussed.

PMID- 11580389
TI  - Dynamics of supercooled water in configuration space.
AB  - We study the potential energy surface (PES) sampled by a liquid modeled via the
      widely studied extended simple point charge (SPC/E) model for water. We
      characterize the curvature of the PES by calculating the instantaneous normal
      mode (INM) spectrum for a wide range of densities and temperatures. We discuss
      the information contained in the INM density of states, which requires additional
      processing to be unambiguously associated with the long-time dynamics. For the
      SPC/E model, we find that the slowing down of the dynamics in the supercooled
      region-where the ideal mode coupling theory has been used to describe the
      dynamics-is controlled by the reduction in the number of directions in
      configuration space that allow a structural change. We find that the fraction
      f(dw) of the double-well directions in configuration space determines the value
      of the diffusion constant D, thereby relating a property of the PES to a
      macroscopic dynamic quantity; specifically, it appears that square root D is
      approximately linear in f(dw). Our findings are consistent with the hypothesis
      that, at the mode coupling crossover temperature, dynamical processes based on
      the free exploration of configuration space vanish, and processes requiring
      activation dominate. Hence, the reduction of the number of directions allowing
      free exploration of configuration space is the mechanism of diffusion implicitly
      implemented in the ideal mode coupling theory. Additionally, we find a direct
      relationship between the number of basins sampled by the system and the number of
      free directions. In this picture, diffusion appears to be related to geometrical
      properties of the PES, and to be entropic in origin.

PMID- 11580391
TI  - Higher-order moments at the critical point of the Ziff-Gulari-Barshad model.
AB  - We studied the continuous phase transition between the active and the absorbing
      state of the Ziff-Gulari-Barshad (ZGB) model. Through Monte Carlo simulations we
      determined all the moments of the order parameter up to fourth order and their
      ratios at the critical point. We show that the ratios we found are in agreement
      with those of the contact and pair contact processes in two dimensions, which
      give support to the idea that the ZGB model is in the directed percolation
      universality class in (2+1) dimensions.

PMID- 11580392
TI  - Fractal and chaotic behavior of circular cellular automata.
AB  - A new type of circular cellular automata (CCA) has been introduced. The
      evolutions of the CCA obtained by the clockwise, anticlockwise, and scanning line
      by-line site sequence in the successively growing rings divided from a square
      lattice are studied. The evolution seems to form a twisty fishnet when the CCA
      are grown by the first two sequences. Sierpinski triangle gasket or the modulated
      ones are formed in the fourth quadrant of the CCA grown by the line scanning
      sequence. Fractal analysis is used to characterize the relationships between the
      pattern formed and the initial position of the growing ring and it is found that
      the pattern is very sensitive to the initial growth condition, showing the
      chaotic behavior.

PMID- 11580393
TI  - Topological properties of citation and metabolic networks.
AB  - Topological properties of "scale-free" networks are investigated by determining
      their spectral dimensions d(S), which reflect a diffusion process in the
      corresponding graphs. Data bases for citation networks and metabolic networks
      together with simulation results from the growing network model [A.-L. Barabasi
      and R. Albert, Science 286, 509 (1999)] are probed. For completeness and
      comparisons lattice, random and small-world models are also investigated. We find
      that d(S) is around 3 for citation and metabolic networks, which is significantly
      different from the growing network model, for which d(S) is approximately 7.5.
      This signals a substantial difference in network topology despite the observed
      similarities in vertex-order distributions. In addition, the diffusion analysis
      indicates that the citation networks are treelike in structure, whereas the
      metabolic networks contain many loops.

PMID- 11580395
TI  - Stochastic exclusion processes with extended hopping.
AB  - We study the effects of extended hopping in the stochastic asymmetric simple
      exclusion process (ASEP) of one dimension. A modified ASEP with four parameters
      is proposed. The current and bulk density are calculated. Two different phases
      with a curved boundary are observed. The phase of maximum current is absent. We
      also present the unusual density fluctuations near both boundaries. The
      characteristic of the stochastic dynamics with extended hopping is pointed out.

PMID- 11580394
TI  - Exact time-dependent correlation functions for the symmetric exclusion process
      with open boundary.
AB  - As a simple model for single-file diffusion of hard core particles we investigate
      the one-dimensional symmetric exclusion process. We consider an open semi
      infinite system where one end is coupled to an external reservoir of constant
      density rho(*) and which initially is in a nonequilibrium state with bulk density
      rho(0). We calculate the exact time-dependent two-point density correlation
      function C(k,l)(t) identical with<n(k)(t)n(l)(t)>-<n(k)(t)><n(l)(t)> and the mean
      and variance of the integrated average net flux of particles N(t)-N(0) that have
      entered (or left) the system up to time t. We find that the boundary region of
      the semi-infinite relaxing system is in a state similar to the bulk state of a
      finite stationary system driven by a boundary gradient. The symmetric exclusion
      model provides a rare example where such behavior can be proved rigorously on the
      level of equal-time two-point correlation functions. Some implications for the
      relaxational dynamics of entangled polymers and for single-file diffusion in
      colloidal systems are discussed.

PMID- 11580396
TI  - Monte Carlo study of the three-dimensional Coulomb frustrated Ising ferromagnet.
AB  - We have investigated, by Monte Carlo simulation, the phase diagram of a three
      dimensional Ising model with nearest-neighbor ferromagnetic interactions and
      small, but long-range (Coulombic) antiferromagnetic interactions. We have
      developed an efficient cluster algorithm and used different lattice sizes and
      geometries, which allows us to obtain the main characteristics of the temperature
      frustration phase diagram. Our finite-size scaling analysis confirms that the
      melting of the lamellar phases into the paramagnetic phase is driven first order
      by the fluctuations. Transitions between ordered phases with different modulation
      patterns are observed in some regions of the diagram, in agreement with a recent
      mean-field analysis.

PMID- 11580398
TI  - Universal magnetic fluctuations with a field-induced length scale.
AB  - We calculate the probability density function for the order-parameter
      fluctuations in the low-temperature phase of the two-dimensional XY model of
      magnetism near the line of critical points. A finite correlation length xi, is
      introduced with a small magnetic field h, and an expression for xi(h) is
      developed by treating nonlinear contributions to the field energy using a Hartree
      approximation. We find analytically a series of universal non-Gaussian
      distributions of the finite-size scaling form P(m,L,xi) approximately
      L(beta/nu)P(L)(mL(beta/nu),xi/L) and present a function of the form P(x)
      approximately [exp[x-exp(x)]](a(h)) that gives the probability density functions
      to an excellent approximation. We propose a(h) as an indirect measure of the
      length scale of correlations in a wide range of complex systems.

PMID- 11580397
TI  - Dynamic finite-size scaling of the normalized height distribution in kinetic
      surface roughening.
AB  - Using well-known simple growth models, we have studied the dynamic finite-size
      scaling theory for the normalized height distribution of a growing surface. We
      find a simple functional form that explains size-dependent behavior of the
      skewness and kurtosis in the transient regime, and obtain the transient- and long
      time values of the skewness and kurtosis for the models. Scaled distributions of
      the models are obtained, and the shape of each distribution is discussed in terms
      of the interfacial width, skewness, and kurtosis, and compared with those for
      other models. Exponents eta(+) and eta(-), which characterize the form of the
      distribution, are determined from an exponential fitting of scaling functions.
      Our detailed results reveal that eta(+)+eta(-) approximately 4 for a model
      obeying usual scaling in contrast to eta(+)+eta(-)<4 with eta(-)=1 for a model
      exhibiting anomalous scaling as well as multiscaling. Since we obtain eta(+)+eta(
      ) approximately 4 for a model exhibiting anomalous scaling but no multiscaling,
      we conclude that the deviation from eta(+)+eta(-) approximately 4 is due to the
      presence of multiscaling behavior in a model.

PMID- 11580399
TI  - Ground state nonuniversality in the random-field Ising model.
AB  - Two attractive and often used ideas, namely, universality and the concept of a
      zero-temperature fixed point, are violated in the infinite-range random-field
      Ising model. In the ground state we show that the exponents can depend
      continuously on the disorder and so are nonuniversal. However, we also show that
      at finite temperature the thermal order-parameter exponent 1/2 is restored so
      that temperature is a relevant variable. Broader implications of these results
      are discussed.

PMID- 11580400
TI  - Necessary conditions for density classification by cellular automata.
AB  - Classifying the initial configuration of a binary-state cellular automaton (CA)
      as to whether it contains a majority of 0s or 1s-the so-called density
      classification problem-has been studied over the past decade by researchers
      wishing to glean an understanding of how locally interacting systems compute
      global properties. In this paper we prove two necessary conditions that a CA must
      satisfy in order to classify density: (1) the density of the initial
      configuration must be conserved over time, and (2) the rule table must exhibit a
      density of 0.5.

PMID- 11580402
TI  - Cluster expansions in dilute systems: applications to satisfiability problems and
      spin glasses.
AB  - We develop a systematic cluster expansion for dilute systems in the highly dilute
      phase. We first apply it to the calculation of the entropy of the K
      satisfiability problem in the satisfiable phase. We derive a series expansion in
      the control parameter, the average connectivity, that is identical to the one
      obtained by using the replica approach with a replica symmetric (RS) ansatz, when
      the order parameter is calculated via a perturbative expansion in the control
      parameter. As a second application we compute the free energy of the Viana-Bray
      model in the paramagnetic phase. The cluster expansion allows one to compute
      finite-size corrections in a simple manner, and these are particularly important
      in optimization problems. Importantly enough, these calculations prove the
      exactness of the RS ansatz below the percolation threshold, and might require its
      revision between this and the easy-to-hard transition.

PMID- 11580401
TI  - Crossover and self-averaging in the two-dimensional site-diluted Ising model:
      application of probability-changing cluster algorithm.
AB  - Using the newly proposed probability-changing cluster (PCC) Monte Carlo
      algorithm, we simulate the two-dimensional (2D) site-diluted Ising model. Since
      we can tune the critical point of each random sample automatically with the PCC
      algorithm, we succeed in studying the sample-dependent T(c)(L) and the sample
      average of physical quantities at each T(c)(L) systematically. Using the finite
      size scaling (FSS) analysis for T(c)(L), we discuss the importance of corrections
      to FSS both in the strong-dilution and weak-dilution regions. The critical
      phenomena of the 2D site-diluted Ising model are shown to be controlled by the
      pure fixed point. The crossover from the percolation fixed point to the pure
      Ising fixed point with the system size is explicitly demonstrated by the study of
      the Binder parameter. We also study the distribution of critical temperature
      T(c)(L). Its variance shows the power-law L dependence, L(-n), and the estimate
      of the exponent n is consistent with the prediction of Aharony and Harris [Phys.
      Rev. Lett. 77, 3700 (1996)]. Calculating the relative variance of critical
      magnetization at the sample-dependent T(c)(L), we show that the 2D site-diluted
      Ising model exhibits weak self-averaging.

PMID- 11580403
TI  - Derivation of Poisson and Nernst-Planck equations in a bath and channel from a
      molecular model.
AB  - Permeation of ions from one electrolytic solution to another, through a protein
      channel, is a biological process of considerable importance. Permeation occurs on
      a time scale of micro- to milliseconds, far longer than the femtosecond time
      scales of atomic motion. Direct simulations of atomic dynamics are not yet
      possible for such long-time scales; thus, averaging is unavoidable. The question
      is what and how to average. In this paper, we average a Langevin model of ionic
      motion in a bulk solution and protein channel. The main result is a coupled
      system of averaged Poisson and Nernst-Planck equations (CPNP) involving
      conditional and unconditional charge densities and conditional potentials. The
      resulting NP equations contain the averaged force on a single ion, which is the
      sum of two components. The first component is the gradient of a conditional
      electric potential that is the solution of Poisson's equation with conditional
      and permanent charge densities and boundary conditions of the applied voltage.
      The second component is the self-induced force on an ion due to surface charges
      induced only by that ion at dielectric interfaces. The ion induces surface
      polarization charge that exerts a significant force on the ion itself, not
      present in earlier PNP equations. The proposed CPNP system is not complete,
      however, because the electric potential satisfies Poisson's equation with
      conditional charge densities, conditioned on the location of an ion, while the NP
      equations contain unconditional densities. The conditional densities are closely
      related to the well-studied pair-correlation functions of equilibrium statistical
      mechanics. We examine a specific closure relation, which on the one hand replaces
      the conditional charge densities by the unconditional ones in the Poisson
      equation, and on the other hand replaces the self-induced force in the NP
      equation by an effective self-induced force. This effective self-induced force is
      nearly zero in the baths but is approximately equal to the self-induced force in
      and near the channel. The charge densities in the NP equations are interpreted as
      time averages over long times of the motion of a quasiparticle that diffuses with
      the same diffusion coefficient as that of a real ion, but is driven by the
      averaged force. In this way, continuum equations with averaged charge densities
      and mean-fields can be used to describe permeation through a protein channel.

PMID- 11580404
TI  - Correlation functions, free energies, and magnetizations in the two-dimensional
      random-field Ising model.
AB  - Transfer-matrix methods are used to calculate spin-spin correlation functions
      (G), Helmholtz free energies (f) and magnetizations (m) in the two-dimensional
      random-field Ising model close to the zero-field bulk critical temperature T(c
      0), on long strips of width L=3-18 sites, for binary field distributions.
      Analysis of the probability distributions of G for varying spin-spin distances R
      shows that describing the decay of their averaged values by effective correlation
      lengths is a valid procedure only for not very large R. Connections between field
      and correlation function distributions at high temperatures are established,
      yielding approximate analytical expressions for the latter, which are used for
      computation of the corresponding structure factor. It is shown that, for fixed
      R/L, the fractional widths of correlation-function distributions saturate
      asymptotically with L-2.2. Considering an added uniform applied field h, a
      connection between f(h), m(h), the Gibbs free energy g(m) and the distribution
      function for the uniform magnetization in a zero uniform field, P0(m), is derived
      and first illustrated for pure systems, and then applied for nonzero random
      field. From finite-size scaling and crossover arguments, coupled with numerical
      data, it is found that the width of P0(m) varies against (nonvanishing, but
      small) random-field intensity H0 as H(-3/7)(0).

PMID- 11580405
TI  - Critical behavior of a lattice prey-predator model.
AB  - The critical properties of a simple prey-predator model are revisited. For some
      values of the control parameters, the model exhibits a line of directed
      percolationlike transitions to a single absorbing state. For other values of the
      control parameters one finds a second line of continuous transitions toward an
      infinite number of absorbing states, and the corresponding steady-state exponents
      are mean-field-like. The critical behavior of the special point T (bicritical
      point), where the two transition lines meet, belongs to a different universality
      class. A particular strategy for preparing the initial states used for the
      dynamical Monte Carlo method is devised to correctly describe the physics of the
      system near the second transition line. Relationships with a forest fire model
      with immunization are also discussed.

PMID- 11580406
TI  - Dynamical aspects of an adiabatic piston.
AB  - Dynamical aspects of an adiabatic piston are investigated, based on the mass
      ratio expansion of the master equation for the piston velocity distribution
      function. Simple theory for piston motion and relaxation of an ideal gas in a
      cylinder turns out to reproduce our numerical experiments quantitatively.

PMID- 11580408
TI  - Image restoration using the Q-Ising spin glass.
AB  - We investigate static and dynamic properties of gray-scale image restoration by
      making use of the Q-Ising spin glass model, whose ladder symmetry allows us to
      take in account the distance between two spins. We thus give an explicit
      expression of the Hamming distance between the original and restored images as a
      function of the hyperparameters in the mean field limit. Finally, numerical
      simulations for real-world pictures are carried out to prove the efficiency of
      our model.

PMID- 11580407
TI  - Softening of first-order transition in three-dimensions by quenched disorder.
AB  - We study by extensive Monte Carlo simulations the effect of random bond dilution
      on the phase transition of the three-dimensional four-state Potts model that is
      known to exhibit a strong first-order transition in the pure case. The phase
      diagram in the dilution-temperature plane is determined from the peaks of the
      susceptibility for sufficiently large system sizes. In the strongly disordered
      regime, numerical evidence for softening to a second-order transition induced by
      randomness is given. Here a large-scale finite-size scaling analysis, made
      difficult due to strong crossover effects presumably caused by the percolation
      fixed point, is performed.

PMID- 11580409
TI  - Freezing in random graph ferromagnets.
AB  - Using T=0 Monte Carlo and simulated annealing simulation, we study the energy
      relaxation of ferromagnetic Ising and Potts models on random graphs. In addition
      to the expected exponential decay to a zero energy ground state, a range of
      connectivities for which there is power law relaxation and freezing to a
      metastable state is found. For some connectivities this freezing persists even
      using simulated annealing to find the ground state. The freezing is caused by
      dynamic frustration in the graphs, and is a feature of the local search nature of
      the Monte Carlo dynamics used. The implications of the freezing on agent-based
      complex system models are briefly considered.

PMID- 11580410
TI  - Short-time critical dynamics of the two-dimensional random-bond Ising model.
AB  - With Monte Carlo simulations we investigate the nonequilibrium critical dynamic
      behavior of the two-dimensional random-bond Ising model. Based on the short-time
      dynamic scaling form, we estimate all the static and dynamic exponents from
      dynamic processes starting with both disordered and ordered states. Corrections
      to scaling are carefully considered.

PMID- 11580411
TI  - Generalized contact process with n absorbing states.
AB  - We investigate the critical properties of a one-dimensional stochastic lattice
      model with n (permutation symmetric) absorbing states. We analyze the cases with
      n</=4 by means of the nonhermitian density-matrix renormalization group. For n=1
      and n=2 we find that the model is, respectively, in the directed percolation and
      parity conserving universality class, consistent with previous studies. For n=3
      and n=4, the model is in the active phase in the whole parameter space and the
      critical point is shifted to the limit of one infinite reaction rate. We show
      that in this limit, the dynamics of the model can be mapped onto that of a zero
      temperature n-state Potts model. On the basis of our numerical and analytical
      results, we conjecture that the model is in the same universality class for all
      n>/=3 with exponents z=nu( ||)/nu( perpendicular)=2, nu( perpendicular)=1, and
      beta=1. These exponents coincide with those of the multispecies (bosonic)
      branching annihilating random walks. For n=3 we also show that, upon breaking the
      symmetry to a lower one (Z2), one gets a transition either in the directed
      percolation, or in the parity conserving class, depending on the choice of
      parameters.

PMID- 11580413
TI  - Exact results of a generalized Wu model with two- and four-spin interactions.
AB  - The mixed spin-1/2 and spin-S(B) Ising model with two- and four-spin interactions
      on the honeycomb lattice is studied by the use of a generalized star-triangle
      transformation. The exact results for the phase diagrams, magnetization,
      correlation functions, internal energy, specific heat, and quadrupolar
      susceptibility are obtained and discussed.

PMID- 11580412
TI  - Possible physical meaning of the Tsallis entropy parameter.
AB  - Since the proposal of the Tsallis generalized entropy, the general explanation of
      the role played by the parameter q that defines which specific entropy to pick
      among a whole family, remained somewhat partial and tentative, although some
      particular examples were taken into account specifically. The purpose of the
      present paper is to present a rigorous formal derivation of a mathematical
      expression giving the parameter q in terms of the momentum fluctuations of a
      stochastic process, thus furnishing at least one of its possible physical
      origins.

PMID- 11580414
TI  - Normal scaling in globally conserved interface-controlled coarsening of fractal
      clusters.
AB  - We find that globally conserved interface-controlled coarsening of diffusion
      limited aggregates exhibits dynamic scale invariance (DSI) and normal scaling.
      This is demonstrated by a numerical solution of the Ginzburg-Landau equation with
      a global conservation law. The general sharp-interface limit of this equation is
      introduced and reduced to volume preserving motion by mean curvature. A simple
      example of globally conserved interface-controlled coarsening system: the
      sublimation/deposition dynamics of a solid and its vapor in a small closed
      vessel, is presented in detail. The results of the numerical simulations show
      that the scaled form of the correlation function has a power-law tail
      accommodating the fractal initial condition. The coarsening length exhibits
      normal dynamic scaling. A decrease of the cluster radius with time, predicted by
      DSI, is observed. The difference between global and local conservation is
      discussed.

PMID- 11580415
TI  - Observations of transient high temperature vortical microstructures in solids
      during adiabatic shear banding.
AB  - By using a unique infrared high-speed camera especially constructed for recording
      highly transient temperature fields at the microscale, we are able to reveal the
      spatial and temporal microstructure within dynamically growing shear bands in
      metals. It is found that this structure is highly nonuniform and possesses a
      transient, short range periodicity in the direction of shear band growth in the
      form of an array of intense "hot spots" reminiscent of the well-known, shear
      induced hydrodynamic instabilities in fluids. This is contrary to the prevailing
      classical view that describes the deformations and the temperatures within shear
      bands as being essentially one-dimensional fields. These observations are also
      reminiscent of the nonuniform structure of localized shear regions believed to
      exist, at an entirely different length scale, in the earth's lower crust and
      upper mantle.

PMID- 11580416
TI  - On-off convection: Noise-induced intermittency near the convection threshold.
AB  - A phenomenological nonlinear stochastic model of intermittency experimentally
      observed by Behn, Lange, and John [Phys. Rev. E 58, 2047 (1998)] in the
      electrohydrodynamic convection in nematics under dichotomous noise is proposed.
      This has the structure of the two-dimensional Swift-Hohenberg equation for local
      convection variable with fluctuating threshold. Numerical integration of the
      model equation shows intermittent emergence of convective pattern. Its statistics
      are found to obey those known, so far, for on-off intermittency. In the course of
      time, although the pattern intensity changes intermittently, no evident pattern
      change is observed. Adding additive noise, we observe an intermittent change of
      convective pattern.

PMID- 11580417
TI  - Periodic metastable structures in the discrete straight phi4 model.
AB  - For the discrete straight phi(4) model a class of metastable periodic solutions
      is given in the form of Fourier series. From the symmetry consideration, we
      eliminate the harmonics with zero amplitudes and thus, reduce the number of
      degrees of freedom. For the rest of harmonics we establish the hierarchy of their
      significance. For solutions with a small period we give the exact expression of
      energy density in terms of amplitudes of harmonics. Conditions of existence and
      stability of the solutions are discussed. For some limiting cases the approximate
      solutions of different kinds are given. The analytical results are compared with
      the results of numerical study. We also discuss a mechanism of transition from a
      metastable periodic structure into the ground state and apply the results to the
      lock-in transition in dielectric crystals supporting incommensurate phase.

PMID- 11580418
TI  - Two-dimensional oscillatory patterns in semiconductors with point contacts.
AB  - Planar samples of n-GaAs with attached point contacts at different dc voltages
      may display a variety of spatiotemporal patterns arising from the dynamics of
      curved charge dipole waves. Patterns rank from oscillations due to recycling and
      motion of simple quasiplanar or cylindrical wave fronts to more complex patterns
      that include merging and splitting of different fronts. Results of numerical
      simulations are interpreted by means of simple one-dimensional asymptotic
      theories.

PMID- 11580419
TI  - Motion of wave fronts in semiconductor superlattices.
AB  - An analysis of wave front motion in weakly coupled doped semiconductor
      superlattices is presented. If a dimensionless doping is sufficiently large, the
      superlattice behaves as a discrete system presenting front propagation failure
      and the wave fronts can be described near the threshold currents J(i) (i=1,2) at
      which they depin and move. The wave front velocity scales with current as |J
      J(i)|(1/2). If the dimensionless doping is low enough, the superlattice behaves
      as a continuum system and wave fronts are essentially shock waves whose velocity
      obeys an equal area rule.

PMID- 11580421
TI  - Periodic chaotic billiards: quantum-classical correspondence in energy space.
AB  - We investigate the properties of eigenstates and local density of states (LDOS)
      for a periodic two-dimensional rippled billiard, focusing on their quantum
      classical correspondence in energy representation. To construct the classical
      counterparts of LDOS and the structure of eigenstates (SES), the effects of the
      boundary are first incorporated (via a canonical transformation) into an
      effective potential, rendering the one-particle motion in the 2D rippled billiard
      equivalent to that of two interacting particles in 1D geometry. We show that
      classical counterparts of SES and LDOS in the case of strong chaotic motion
      reveal quite a good correspondence with the quantum quantities. We also show that
      the main features of the SES and LDOS can be explained in terms of the underlying
      classical dynamics, in particular, of certain periodic orbits. On the other hand,
      statistical properties of eigenstates and LDOS turn out to be different from
      those prescribed by random matrix theory. We discuss the quantum effects
      responsible for the nonergodic character of the eigenstates and individual LDOS
      that seem to be generic for this type of billiards with a large number of
      transverse channels.

PMID- 11580420
TI  - Complex Ginzburg-Landau equation in the presence of walls and corners.
AB  - We investigate the influence of walls and corners (with Dirichlet and Neumann
      boundary conditions) in the evolution of two-dimensional autooscillating fields
      described by the complex Ginzburg-Landau equation. Analytical solutions are
      found, and arguments provided, to show that Dirichlet walls introduce strong
      selection mechanisms for the wave pattern. Corners between walls provide
      additional synchronization mechanisms and associated selection criteria. The
      numerical results fit well with the theoretical predictions in the parameter
      range studied.

PMID- 11580422
TI  - Entangling power of quantized chaotic systems.
AB  - We study the quantum entanglement caused by unitary operators that have classical
      limits that can range from the near integrable to the completely chaotic.
      Entanglement in the eigenstates and time-evolving arbitrary states is studied
      through the von Neumann entropy of the reduced density matrices. We demonstrate
      that classical chaos can lead to substantially enhanced entanglement. Conversely,
      entanglement provides a useful characterization of quantum states in higher
      dimensional chaotic or complex systems. Information about eigenfunction
      localization is stored in a graded manner in the Schmidt vectors, and the
      principal Schmidt vectors can be scarred by the projections of classical periodic
      orbits onto subspaces. The eigenvalues of the reduced density matrices is
      sensitive to the degree of wave-function localization, and is roughly
      exponentially arranged. We also point out the analogy with decoherence, as
      reduced density matrices corresponding to subsystems of fully chaotic systems,
      are diagonally dominant.

PMID- 11580423
TI  - Imperfect homoclinic bifurcations.
AB  - Experimental observations of an almost symmetric electronic circuit show
      complicated sequences of bifurcations. These results are discussed in the light
      of a theory of imperfect global bifurcations. It is shown that much of the
      dynamics observed in the circuit can be understood by reference to imperfect
      homoclinic bifurcations without constructing an explicit mathematical model of
      the system.

PMID- 11580425
TI  - Role of transient processes for reconstruction of model equations from time
      series.
AB  - We perform a global reconstruction of differential and difference equations,
      which model an object in a wide domain of a phase space, from a time series. The
      efficiency of using time realizations of transient processes for this purpose is
      demonstrated. Time series of transients are shown to have some advantages for the
      realization of a procedure of model structure optimization.

PMID- 11580424
TI  - Unveiling the topological structure of chaotic flows from data.
AB  - We report the analysis of branched manifolds through homologies, in order to
      extend the range of applicability of the topological approach to the analysis of
      chaotic data. Analytic and numerical cases are discussed.

PMID- 11580426
TI  - Parametric correlations of the energy levels of ray-splitting billiards.
AB  - Parameter-dependent statistical properties of the spectra of ray-splitting
      billiards are studied experimentally and theoretically. The autocorrelation
      functions c(x) and c(omega,x) of level velocities as well as the generalized
      conductance C(0) are calculated for two different classically chaotic ray
      splitting billiards. Experimentally a modified Sinai ray-splitting billiard is
      studied consisting of a thin microwave rectangular cavity with two quarter-circle
      shaped Teflon inserts. The length of the cavity serves as the experimentally
      adjustable parameter. For the theoretical estimates of the parametric
      correlations we compute the quantum spectrum of a scaling triangular ray
      splitting billiard. Our experimental and numerical results are compared with each
      other and with the predictions of random matrix theory.

PMID- 11580427
TI  - Bifurcations in annular electroconvection with an imposed shear.
AB  - We report an experimental study of the primary bifurcation in electrically driven
      convection in a freely suspended film. A weakly conducting, submicron thick
      smectic liquid crystal film was supported by concentric circular electrodes. It
      electroconvected when a sufficiently large voltage V was applied between its
      inner and outer edges. The film could sustain rapid flows and yet remain strictly
      two dimensional. By rotation of the inner electrode, a circular Couette shear
      could be independently imposed. The control parameters were a dimensionless
      number R, analogous to the Rayleigh number, which is ~V2 and the Reynolds number
      Re of the azimuthal shear flow. The geometrical and material properties of the
      film were characterized by the radius ratio alpha, and a dimensionless number P,
      analogous to the Prandtl number. Using measurements of current-voltage
      characteristics of a large number of films, we examined the onset of
      electroconvection over a broad range of alpha, P, and Re. We compared this data
      quantitatively to the results of linear stability theory. This could be done with
      essentially no adjustable parameters. The current-voltage data above onset were
      then used to infer the amplitude of electroconvection in the weakly nonlinear
      regime by fitting them to a steady-state amplitude equation of the Landau form.
      We show how the primary bifurcation can be tuned between supercritical and
      subcritical by changing alpha and Re.

PMID- 11580428
TI  - Dynamics of quantum systems.
AB  - A relation between the eigenvalues of an effective Hamilton operator and the
      poles of the S matrix is derived that holds for isolated as well as for
      overlapping resonance states. The system may be a many-particle quantum system
      with two-body forces between the constituents or it may be a quantum billiard
      without any two-body forces. Avoided crossings of discrete states as well as of
      resonance states are traced back to the existence of branch points in the complex
      plane. Under certain conditions, these branch points appear as double poles of
      the S matrix. They influence the dynamics of open as well as of closed quantum
      systems. The dynamics of the two-level system is studied in detail analytically
      as well as numerically.

PMID- 11580429
TI  - Long-wavelength instabilities of three-dimensional patterns.
AB  - Long-wavelength instabilities of steady patterns, spatially periodic in three
      dimensions, are studied. All potentially stable patterns with the symmetries of
      the simple-, face-centered- and body-centered-cubic lattices are considered. The
      results generalize the well-known Eckhaus, zigzag, and skew-varicose
      instabilities to three-dimensional patterns and are applied to two-species
      reaction-diffusion equations modeling the Turing instability.

PMID- 11580430
TI  - Diffusion of particles bouncing on a one-dimensional periodically corrugated
      floor.
AB  - We report on a class of spatially extended mechanical systems sustaining a
      transport process of diffusive type. These systems consist of a point particle
      subject to a constant vertical acceleration and bouncing on a one-dimensional
      periodically corrugated floor. We show that the deterministic dynamics of these
      systems is chaotic with small elliptic islands for many parameter values. The
      motion of particles perturbed by a small noise has a horizontal diffusion that is
      normal. In such a case, we show that the diffusion coefficient oscillates
      periodically as the energy of particles increases. In the absence of noise, there
      still exists an effective numerical value for the diffusion coefficient and this
      value has an irregular dependence on energy.

PMID- 11580431
TI  - Blowout bifurcation and stability of marginal synchronization of chaos.
AB  - Blowout bifurcations are investigated in a symmetrized extension of the
      replacement method of chaotic synchronization which consists of coupling chaotic
      systems via mutually shared variables. The coupled systems are partly linear with
      respect to variables that are not shared, and that form orthogonal invariant
      manifolds in the composite system. If the coupled systems are identical, marginal
      (projective) synchronization between them occurs. Breaking the symmetry by a
      small variation of the system parameters leads to a new kind of blowout
      bifurcation in which the transverse stability is exchanged between the orthogonal
      invariant manifolds. This bifurcation is neither supercritical nor subcritical.
      The latter scenarios are also observed as the parameters are further varied,
      leading to on-off intermittency and the appearance of riddled basins of
      attraction. Examples using well-known chaotic models are presented.

PMID- 11580432
TI  - Field-dependent collision frequency of the two-dimensional driven random Lorentz
      gas.
AB  - In the field-driven, thermostated Lorentz gas the collision frequency increases
      with the magnitude of the applied field due to long-time correlations. We study
      this effect with computer simulations and confirm the presence of nonanalytic
      terms in the field dependence of the collision rate as predicted by kinetic
      theory.

PMID- 11580433
TI  - Structure and variability of spinning reaction waves in three-dimensional
      excitable media.
AB  - A mathematical simulation for a reaction wave that propagates in a cylindrical
      sample is performed. The propagation modes that have not yet been observed
      experimentally are predicted. The areas of existence for these modes have been
      determined.

PMID- 11580434
TI  - Mechanism of synchronization in a random dynamical system.
AB  - The mechanism of synchronization in the random Zaslavsky map is investigated.
      From the error dynamics of two particles, the structure of phase space was
      analyzed, and a transcritical bifurcation between a saddle and a stable fixed
      point was found. We have verified the structure of on-off intermittency in terms
      of a biased random walk. Furthermore, for the generalized case of the ensemble of
      particles, a modified definition of the size of a snapshot attractor was
      exploited to establish the link with a random walk. As a result, the structure of
      on-off intermittency in the ensemble of particles was explicitly revealed near
      the transition.

PMID- 11580436
TI  - Theory and applications of ray chaos to underwater acoustics.
AB  - Chaotic ray dynamics in deep sea propagation models is considered using the
      approaches developed in the theory of dynamical chaos. It has been demonstrated
      that the mechanism of emergence of ray chaos due to overlapping of nonlinear ray
      medium resonances should play an important role in long range sound propagation.
      Analytical estimations, supported by numerical simulations, show that for
      realistic values of spatial periods and sound speed fluctuation amplitudes
      associated with internal-wave-induced perturbations, the resonance overlapping
      causes stochastic instability of ray paths. The influence of the form of the
      smooth unperturbed sound speed profile on ray sensitivity to the perturbation is
      studied. Stability analysis has been conducted by constructing the Poincare maps
      and examining depth differences of ray trajectories with close take-off angles.
      The properties of ray travel times, including fractal properties of the time
      front fine structures, under condition of ray chaos have been investigated. It
      has been shown that the coexistence of chaotic and regular rays, typical for
      dynamical chaos, leads to the appearance of gaps in ray travel time
      distributions, which are absent in unperturbed waveguides. This phenomenon has a
      prototype in theory of dynamical chaos called the stochastic particle
      acceleration. It has been shown that mesoscale inhomogeneities with greater
      spatial scales than that of internal waves, create irregular local waveguide
      channels in the vicinity of the axis (i.e., sound speed minimum) of the
      unperturbed waveguide. Near-axial rays propagating at small grazing angles,
      "jump" irregularly between these microchannels. This mechanism determines chaotic
      behavior of the near-axial rays.

PMID- 11580435
TI  - Entropy production and wave packet dynamics in the Fock space of closed chaotic
      many-body systems.
AB  - Highly excited many-particle states in quantum systems such as nuclei, atoms,
      quantum dots, spin systems, quantum computers, etc., can be considered as
      "chaotic" superpositions of mean-field basis states (Slater determinants,
      products of spin or qubit states). This is due to a very high level density of
      many-body states that are easily mixed by a residual interaction between
      particles (quasiparticles). For such systems, we have derived simple analytical
      expressions for the time dependence of the energy width of wave packets, as well
      as for the entropy, number of principal basis components, and inverse
      participation ratio, and tested them in numerical experiments. It is shown that
      the energy width Delta(t) increases linearly and very quickly saturates. The
      entropy of a system increases quadratically, S(t) approximately t(2), at small
      times, and afterward can grow linearly, S(t) approximately t, before saturation.
      Correspondingly, the number of principal components determined by the entropy
      N(pc) approximately exp[S(t)] or by the inverse participation ratio increases
      exponentially fast before saturation. These results are explained in terms of a
      cascade model which describes the flow of excitation in the Fock space of basis
      components. Finally, the striking phenomenon of damped oscillations in the Fock
      space at the transition to equilibrium is discussed.

PMID- 11580437
TI  - Distribution of nearest distances between nodal points for the Berry function in
      two dimensions.
AB  - According to Berry a wave-chaotic state may be viewed as a superposition of
      monochromatic plane waves with random phases and amplitudes. Here we consider the
      distribution of nodal points associated with this state. Using the property that
      both the real and imaginary parts of the wave function are random Gaussian fields
      we analyze the correlation function and densities of the nodal points. Using two
      approaches (the Poisson and Bernoulli) we derive the distribution of nearest
      neighbor separations. Furthermore the distribution functions for nodal points
      with specific chirality are found. Comparison is made with results from numerical
      calculations for the Berry wave function.

PMID- 11580438
TI  - Multistability in dynamical systems induced by weak periodic perturbations.
AB  - It is shown that weak resonant perturbations at subharmonic frequencies can
      induce multistability in a wide class of nonlinear systems, which display the
      period-doubling route into chaos or possess isolated subharmonic branches. The
      number of attractors induced depends on the subharmonic frequency, amplitude, and
      phase of periodic perturbations, as well as an initial dynamical state of
      nonlinear systems. Experimental and numerical evidences are given on the basis of
      a loss-modulated CO2 laser.

PMID- 11580439
TI  - Dynamics of coupling functions in globally coupled maps: size, periodicity, and
      stability of clusters.
AB  - It is shown how different globally coupled map systems can be analyzed under a
      common framework by focusing on the dynamics of their respective global coupling
      functions. We investigate how the functional form of the coupling determines the
      formation of clusters in a globally coupled map system and the resulting
      periodicity of the global interaction. The allowed distributions of elements
      among periodic clusters is also found to depend on the functional form of the
      coupling. Through the analogy between globally coupled maps and a single driven
      map, the clustering behavior of the former systems can be characterized. By using
      this analogy, the dynamics of periodic clusters in systems displaying a constant
      global coupling are predicted; and for a particular family of coupling functions,
      it is shown that the stability condition of these clustered states can
      straightforwardly be derived.

PMID- 11580440
TI  - Eigenstate structure in graphs and disordered lattices.
AB  - We study wave function structure for quantum graphs in the chaotic and disordered
      regime, using measures such as the wave function intensity distribution and the
      inverse participation ratio. The result is much less ergodicity than expected
      from random matrix theory, even though the spectral statistics are in agreement
      with random matrix predictions. Instead, analytical calculations based on short
      time semiclassical behavior correctly describe the eigenstate structure.

PMID- 11580441
TI  - Inertial range determination for aerothermal turbulence using fractionally
      differenced processes and wavelets.
AB  - A fractionally differenced (FD) process is used to model aerothermal turbulence
      data, and the model parameters are estimated via wavelet techniques. Theory and
      results are presented for three estimators of the FD parameter: an
      "instantaneous" block-independent least squares estimator and block-dependent
      weighted least squares and maximum likelihood estimators. Confidence intervals
      are developed for the block-dependent estimators. We show that for a majority of
      the aerothermal turbulence data studied herein, there is a strong departure from
      the theoretical Kolmogorov turbulence over finite ranges of scale. A time-scale
      dependent inertial range statistic is developed to quantify this departure.

PMID- 11580442
TI  - Intermittency and coherent structures in the two-dimensional inverse energy
      cascade: comparing numerical and laboratory experiments.
AB  - We study the internal intermittency in the inverse energy cascade and in the
      condensation regime of two-dimensional turbulence, using physical and numerical
      experimental approaches. The analysis confirms that the velocity increments have
      nearly Gaussian distributions at all scales in the inverse cascade regime; it
      moreover shows that, in the condensation regime, the probability distribution
      functions of the velocity increments are non-Gaussian but do not significantly
      vary with the scale; it follows that one may consider that there is essentially
      no intermittency (in the usual sense), in the condensation regime. In both
      regimes, we emphasize that coherent structures (i.e., long-lived vortices) are
      clearly visible on the vorticity field, and we suggest the non-Gaussianity of the
      distributions in the condensation regime is due to the presence of a large-scale
      long-lived structures. The study is supplemented by the analysis of the
      distribution of energy transfers at various scales.

PMID- 11580443
TI  - Non-Newtonian effects in the peristaltic flow of a Maxwell fluid.
AB  - We analyzed the effect of viscoelasticity on the dynamics of fluids in porous
      media by studying the flow of a Maxwell fluid in a circular tube, in which the
      flow is induced by a wave traveling on the tube wall. The present paper
      investigates phenomena brought about into the classic peristaltic mechanism by
      inclusion of non-Newtonian effects that are important, e.g., for hydrocarbons.
      This problem has numerous applications in various branches of science, including
      the stimulation of fluid flow in a porous media under the effect of elastic waves
      and studies of blood flow dynamics in living creatures. We have found that in the
      extreme non-Newtonian regime, there is a possibility of a fluid flow in the
      direction opposite to the propagation of the wave traveling on the tube wall.

PMID- 11580444
TI  - Large-scale velocity structures in turbulent thermal convection.
AB  - A systematic study of large-scale velocity structures in turbulent thermal
      convection is carried out in three different aspect-ratio cells filled with
      water. Laser Doppler velocimetry is used to measure the velocity profiles and
      statistics over varying Rayleigh numbers Ra and at various spatial positions
      across the whole convection cell. Large velocity fluctuations are found both in
      the central region and near the cell boundary. Despite the large velocity
      fluctuations, the flow field still maintains a large-scale quasi-two-dimensional
      structure, which rotates in a coherent manner. This coherent single-roll
      structure scales with Ra and can be divided into three regions in the rotation
      plane: (1) a thin viscous boundary layer, (2) a fully mixed central core region
      with a constant mean velocity gradient, and (3) an intermediate plume-dominated
      buffer region. The experiment reveals a unique driving mechanism for the large
      scale coherent rotation in turbulent convection.

PMID- 11580445
TI  - Slow inviscid flows of a compressible fluid in spatially inhomogeneous systems.
AB  - An ideal compressible fluid is considered, with an equilibrium density being a
      given function of coordinates due to presence of some static external forces. The
      slow flows in such system, which do not disturb the density, are investigated
      with the help of the Hamiltonian formalism. The equations of motion of the system
      are derived for an arbitrary given topology of the vorticity field. The general
      form of the Lagrangian for frozen-in vortex lines is established. The local
      induction approximation for motion of slender vortex filaments in several
      inhomogeneous physical models is studied.

PMID- 11580446
TI  - Kinematics of small scale anisotropy in turbulence.
AB  - A simple, empirically motivated model is proposed to explain the transfer of
      imposed large scale anisotropy to small scales in high-Reynolds-number
      turbulence. Observed power-law scalings of anisotropy metrics are interpreted as
      manifestations of power-law scalings governing high-gradient regions resulting
      from compressional eddy motions. The model is used to interpret the measured
      moment-order dependencies of the exponents and amplitudes of odd-order structure
      functions and derivative moments that vanish in the absence of anisotropy.

PMID- 11580447
TI  - Influence of the thermoelectric effect on the Rayleigh-Benard instability inside
      a magnetic field.
AB  - We investigate the influence of thermoelectric effect on the onset of thermal
      instability in the Rayleigh-Benard system with vertical magnetic field. An
      electrically conducting fluid is confined in an infinite horizontal layer between
      thick thermally and electrically conducting walls. A horizontal temperature
      variation resulting from convective instability leads to horizontal temperature
      gradients along the liquid-solid interface acting as a source of thermoelectric
      currents. Through interaction with the applied magnetic field, the Lorentz force
      is created modifying the instability. We find that the critical Rayleigh number
      for onset of convection is not changed by the thermoelectric effect. However, the
      thermal gradient on the liquid-solid boundary leads to a change of the shape of
      the unstable mode creating helical flow in the evolving convection rolls because
      of the Lorentz force parallel to their axis. The created kinetic helicity depends
      linearly on the dimensionless parameter K(TE) characterizing the strength of the
      thermoelectric effect.

PMID- 11580448
TI  - Dust-acoustic modes in self-gravitating plasmas with dust size distributions.
AB  - Using a kinetic description, dust-acoustic waves are considered for dusty plasmas
      containing, besides the electrons and ions, dust particles with continuous mass
      (size) distributions. For broad size spectra, self-gravitational effects cannot
      be neglected anymore because in the competition between electromagnetic and
      gravitational forces, the scale tips over towards gravitation for the heavier
      dust grains. Self-gravitational effects are clearly interwoven with the grain
      size distribution and here the effects of different power-law size distributions
      on the propagation, damping, and instability of low-frequency waves are
      discussed.

PMID- 11580450
TI  - He metastable density in a double layer formed by a diameter discontinuity in a
      positive column.
AB  - The population density profile of triplet metastable He (2 3S1) is measured in
      the multiple space-charge (double) layer formed at an abrupt transition of the
      tube diameter in a positive column discharge. The double layer is formed at the
      transition from a 2.6 cm diameter to a 0.6 cm diameter tube in a static pressure
      discharge. The line integrated He 2 3S1 population density profile in the double
      layer region is determined by diode-laser absorption. The triplet metastable
      density profiles are measured with discharge currents of 1, 2, and 5 mA at 1 Torr
      pressure for both polarity conditions: (a) when the cathode end of the discharge
      is in the large diameter tube and (b) when the anode end of the discharge is in
      the large diameter tube. The diode-laser absorption profiles show enhanced
      production of triplet metastable He 2 3S1 in the double-layer region as compared
      to the unperturbed positive column (0.6 cm diameter) with the magnitude being
      strongly dependent on the discharge polarity.

PMID- 11580449
TI  - Spatiotemporal dynamics of charged species in the afterglow of plasmas containing
      negative ions.
AB  - The spatiotemporal evolution of charged species densities and wall fluxes during
      the afterglow of an electronegative discharge has been investigated. The decay of
      a plasma with negative ions consists of two stages. During the first stage of the
      afterglow, electrons dominate plasma diffusion and negative ions are trapped
      inside the vessel by the static electric field; the flux of negative ions to the
      walls is nearly zero. During this stage, the electron escape frequency increases
      considerably in the presence of negative ions, and can eventually approach free
      electron diffusion. During the second stage of the afterglow, electrons have
      disappeared, and positive and negative ions diffuse to the walls with the ion-ion
      ambipolar diffusion coefficient. Theories for plasma decay have been developed
      for equal and strongly different ion (T(i)) and electron (T(e)) temperatures. In
      the case T(i)=T(e), the species spatial profiles are similar and an analytic
      solution exists. When detachment is important in the afterglow (weakly
      electronegative gases, e.g., oxygen) the plasma decay crucially depends on the
      product of negative ion detachment frequency (gamma(d)) and diffusion time
      (tau(d)). If gamma(d)tau(d)>2, negative ions convert to electrons during their
      diffusion towards the walls. The presence of detached electrons results in "self
      trapping" of the negative ions, due to emerging electric fields, and the negative
      ion flux to the walls is extremely small. In the case T(i)<<T(e), the
      spatiotemporal dynamics is more complicated due to the presence of negative ion
      density fronts. During the afterglow, although negative ions diffuse freely in
      the plasma core, the negative ion fronts propagate towards the chamber walls with
      a nearly constant velocity. The evolution of ion fronts in the afterglow of
      electronegative plasmas is important, since it determines the time needed for
      negative ions to reach the wall, and thus influence surface reactions in plasma
      processing.

PMID- 11580452
TI  - Probability density function model equation for particle charging in a
      homogeneous dusty plasma.
AB  - In this paper, we use the direct interaction approximation (DIA) to obtain an
      approximate integrodifferential equation for the probability density function
      (PDF) of charge (q) on dust particles in homogeneous dusty plasma. The DIA is
      used to solve the closure problem which appears in the PDF equation due to the
      interactions between the phase space density of plasma particles and the phase
      space density of dust particles. The equation simplifies to a differential form
      under the condition when the fluctuations in phase space density for plasma
      particles change very rapidly in time and is correlated for very short times. The
      result is a Fokker-Planck type equation with extra terms having third and fourth
      order differentials in q, which account for the discrete nature of distribution
      of plasma particles and the interaction between fluctuations. Approximate
      macroscopic equations for the time evolution of the average charge and the higher
      order moments of the fluctuations in charge on the dust particles are obtained
      from the differential PDF equation. These equations are computed, in the case of
      a Maxwellian plasma, to show the effect of density fluctuations of plasma
      particles on the statistics of dust charge.

PMID- 11580451
TI  - Absolute extreme ultraviolet yield from femtosecond-laser-excited Xe clusters.
AB  - Large Xe clusters (10(5)-10(6) atoms per cluster) have been irradiated with
      ultrashort (50 fs) and high-intensity ( approximately 2 x 10(18) W/cm(2)) pulses
      from a Ti:sapphire multi-TW laser at 800 nm wavelength. Scaling and absolute
      yield measurements of extreme ultraviolet (EUV) emission in a wavelength range
      between 7 and 15 nm in combination with cluster target characterization have been
      used for yield optimization. Maximum emission as a function of the backing
      pressure and a spatial emission anisotropy covering a factor of two at optimized
      yields is discussed with a simple model of the source geometry and EUV-radiation
      absorption. Circularly polarized laser light instead of linear polarization
      results in a factor of 2.5 higher emission in the 11 to 15 nm wavelength range.
      This indicates the initial influence of optical-field ionization for the
      interaction parameter range used and contrasts to collisional heating that seems
      to influence preferentially higher ionization. Absolute emission efficiency at
      13.4 nm of up to 0.5% in 2pi sr and 2.2% bandwidth has been obtained.

PMID- 11580453
TI  - Observations of the vacuum ultraviolet and x-ray brightness profiles of Fe, Ni,
      and Ge in magnetically confined fusion plasmas.
AB  - The spatial brightness profiles of emission lines for the K-like through He-like
      ionization states of Fe, Ge, and Ni have been measured during a set of
      experiments in which Fe and Ge were introduced into FTU tokamak plasmas by using
      the laser blowoff technique. Nickel was an intrinsic impurity observed during
      these experiments that was sputtered from the inconel limiter. The brightness
      profiles were measured by spatially scanable, photometrically calibrated vaccum
      ultraviolet and x-ray spectrometers that covered the 1 to 1700 A region.
      Simulations of these profiles and the time evolution of the laser blowoffs were
      performed with the MIST transport code using several sets of atomic physics
      compilations [ADPAK (originally in MIST), Arnaud and Raymond (AR92), Arnaud and
      Rothenflug (AR85), Mazzotta et al., and Mattioli (an extension to Mazzotta)]. The
      goal was to determine which set of available rates could best simulate the
      measured spatial brightness profiles and the charge state balance in the plasma.
      The Mazzotta et al. (for Fe and Ni), the Mattioli (for Ge), and the AR92 (for Fe
      only) rates adequately simulated the He-, Li-, Be-, Na-, Mg-like ionization
      states. The F- to B-like charge states could not be simulated by these
      compilations unless the relevant dielectronic rates were multiplied by a factor
      of 2. The ADPAK rates could not adequately predict any of the charge states of
      Fe, Ge, or Ni.

PMID- 11580454
TI  - Photon acceleration based on plasma.
AB  - A formalism is presented to examine the interaction of laser field with plasma
      wave in which the interaction is described as some geometric metric (optical
      metric) and then a laser beam is treated as a packet of photons moving along null
      geodesics with respect to that metric. Photon motion equations are derived and
      solved analytically in both the one-dimensional and the three-dimensional cases.
      The expressions for the frequency shifts of laser pulses are presented and it is
      found that the frequency shifting results from the plasma density gradient. Three
      dimensional solution shows that a laser beam diffraction occurs in the presence
      of a radial variation of the plasma density. It is argued that the focusing
      mechanism originated from the plasma wave can curb laser diffracting, so that
      photons can be trapped in the plasma wave and accelerated continuously.

PMID- 11580456
TI  - Dissipative Toda-Rayleigh lattice and its oscillatory modes.
AB  - A detailed theoretical and experimental analysis of the possible oscillatory
      regimes of the dissipative Toda-Rayleigh lattice system is provided. It is shown
      that the system has (N-1) oscillatory modes with different space-time scales and
      two rotatory modes. Using its analog electronic circuit implementation we also
      show with a simple and robust method how switching between modes occurs.

PMID- 11580455
TI  - Effect of electron-beam momentum spread on cyclotron resonance maser operation at
      two resonant frequencies.
AB  - We present a theoretical analysis of cyclotron resonance maser (CRM) operation at
      two resonant frequencies including the effects of momentum spread in the electron
      beam. A linear analysis of the system equations is presented in the limit of
      small momentum spreads. Numerical solutions to the system equations are also
      given and are in agreement with the linear theory. The results predict that for
      realistic momentum spreads, operation of the CRM at the higher of the two
      resonant frequencies should be possible, extending its operating frequency range.
      An experiment currently under development at Strathclyde University is described
      and modeled numerically.

PMID- 11580457
TI  - Theoretical and experimental study of two discrete coupled Nagumo chains.
AB  - We analyze front wave (kink and antikink) propagation and pattern formation in a
      system composed of two coupled discrete Nagumo chains using analytical and
      numerical methods. In the case of homogeneous interaction among the chains, we
      show the possibility of the effective control on wave propagation. In addition,
      physical experiments on electrical chains confirm all theoretical behaviors.

PMID- 11580458
TI  - Helical harmonics for static fields.
AB  - Helical harmonic solutions of Laplace's equation are derived using a right-handed
      nonorthogonal helical coordinate system and a modified separation of variables
      technique. Unlike the Cartesian or cylindrical coordinate systems, in the helical
      system, two different sets of solutions are admitted, one right handed and one
      left handed. Consequently, the helical harmonics are used to solve the boundary
      value problem of two nested helices with different radii set to different
      potential values.

PMID- 11580459
TI  - Optical tunneling of single-cycle terahertz bandwidth pulses.
AB  - We report time-domain measurements with subpicosecond resolution of optical
      tunneling of terahertz electromagnetic pulses undergoing frustrated total
      internal reflection. Measurements of the transmitted electromagnetic pulses over
      a 3 THz bandwidth permits direct determination of frequency-dependent phase and
      amplitude changes in both the thin and opaque barrier limits in a single
      measurement. A complex frequency response function describing propagation through
      the barrier is developed based upon linear dispersion theory and the Fresnel
      coefficients at complex angles in the optical barrier. Our measurements are in
      excellent agreement with this theoretical model across the experimentally
      determined bandwidth; the model makes no assumptions about the beam path through
      the barrier and has no adjustable parameters. The theory is shown to satisfy the
      Kramers-Kronig relations, indicating causal propagation across the barrier.

PMID- 11580460
TI  - Random multiple scattering of ultrasound. I. Coherent and ballistic waves.
AB  - This is the first article in a series of two dealing with the statistical moments
      of ultrasonic waves transmitted through a disordered medium with resonant
      multiple scattering. Only the first-order moment is considered here. An
      ultrasonic pulsed wave is transmitted from a point source to a 128-element
      receiving array through two-dimensional samples with various thicknesses. The
      samples consist of random collections of parallel steel rods immersed in water.
      Experimental results show that the ensemble-averaged transmitted wave forms
      ("coherent wave") exhibit a time-dependent frequency spectrum. Within the
      independent scattering approximation, this is well explained by individual
      resonances of the scatterers. The coherent wave only appears after ensemble
      averaging and has to be distinguished from the "ballistic wave," i.e., the first
      well-defined pulse that crosses the sample, which can be measured on every
      realization of disorder. A physical interpretation is given, which is based on
      the separation of the coherent wave between a rigid and a resonant contribution.

PMID- 11580461
TI  - Random multiple scattering of ultrasound. II. Is time reversal a self-averaging
      process?
AB  - This is the second article in a series of two dealing with the statistical
      moments of ultrasonic waves transmitted through a disordered medium with resonant
      multiple scattering. Second-order moments in time and space are considered here.
      An ultrasonic pulsed wave is transmitted from a point source to a 128-element
      receiving array through two-dimensional samples with various thicknesses. The
      samples consist of random collections of parallel steel rods immersed in water.
      The scattered waves are recorded, time reversed, and sent back into the medium.
      The time-reversed waves are converging back to their source and the quality of
      spatial and temporal focusing on the source is related to the second-order
      moments of the scattered wave (correlation) in time and in space. Experimental
      results show that it is possible to obtain a robust estimation on a single
      realization of disorder, taking advantage of the wide frequency bandwidth. The
      spatial resolution of the system is only limited by the correlation length of the
      scattered field, and no longer by the array aperture. As the sample thickness is
      increased, the quality of focusing saturates, which we believe is linked to the
      Thouless factor g. In the thickest sample, g approximately 30, which is still
      well above the localization threshold.

PMID- 11580462
TI  - Spectral dependence of polarized radiation due to spatial correlations.
AB  - We study the polarization of light emitted by spatially correlated sources. We
      show that, in general, polarization acquires a nontrivial spectral dependence due
      to spatial correlations. The spectral dependence is found to be absent only for a
      special class of sources where the correlation length scales as the wavelength of
      light. We further study cross correlations between two spatially distinct points
      that are generated due to propagation. It is found that such cross correlation
      leads to a sufficiently strong spectral dependence of polarization which can be
      measured experimentally.

PMID- 11580464
TI  - Penetration of dynamic localized states in dc-driven Josephson junction ladders
      by discrete jumps.
AB  - We give a theoretical study of unusual resistive (dynamic) localized states in
      anisotropic Josephson junction ladders, driven by a dc current at one edge. These
      states comprise nonlinearly coupled rotating Josephson phases in adjacent cells,
      and with increasing current they are found to expand into neighboring cells by a
      sequence of sudden jumps. We argue that the jumps arise from instabilities in the
      ladder's superconducting part, and our analytic expressions for the peculiar
      voltage (rotational frequency) ratios and I-V curves are in very good agreement
      with direct numerical simulations.

PMID- 11580463
TI  - Probability amplitude description of the dynamics of charged particles in a
      magnetic field in the macrodomain.
AB  - The set of Schrodinger-like equations obtained earlier by the author [Phys. Rev.
      Lett. 26, 417 (1971), Phys. Rev. A 31, 3951 (1985)] for the charged particle
      dynamics in an inhomogeneous magnetic field in the macrodomain, are derived here
      starting from the quantum-mechanic Schrodinger equation in its path-integral
      representation. This derivation enables a generalization of the equations to
      include a curl-free vector potential in the Schrodinger-like equations. In view
      of the amplitude character of the latter equations, which now descends directly
      from that of the quantum-mechanic Schrodinger equation, they now predict the
      existence in the macrodomain of all such phenomena, which are characteristic of a
      probability amplitude theory, e.g., the interference, and the observation of a
      curl-free vector a la Aharonov-Bohm. A discrete energy structure, predicted as
      interference maxima and minima has already been observed by the author with his
      co-workers [Mod. Phys. Lett. A 8, 167 (1993)]. A prediction is now made for the
      observability of a curl-free vector potential in the macrodomain, in the context
      of the present problem.

PMID- 11580465
TI  - Effects of spatial inhomogeneities on the dynamics of cavity solitons in
      quadratically nonlinear media.
AB  - We study the dynamics of cavity solitons under the influence of spatial
      inhomogeneities and derive generalized equations of motions. For perturbations
      large compared to the soliton size we find the modulus of the soliton velocity to
      be proportional to the gradient of the respective perturbation and that the
      proportionality coefficient changes sign when the soliton peak power drives the
      cavity beyond the resonance. For short scale perturbations solitons may be
      trapped at the extrema of the inhomogeneities. Shape and stability of these
      trapped solitons can be quasianalytically described by means of a perturbation
      theory. If both types of perturbations act solitons are either trapped or move
      depending on the strength of the respective perturbation. In the framework of a
      quasiparticle approach this dynamics is governed by a differential equation that
      holds for particle motion in a strongly viscous fluid under the action of a
      constant and harmonically varying force. We also show that in addition to
      acquiring a velocity the very existence conditions of the solitons (hysteresis
      curve) are affected by both kinds of perturbations. We find good quantitative
      agreement between our analytical results and numerical findings, which were
      obtained for a two wave interaction in a cavity filled with a quadratically
      nonlinear material.

PMID- 11580466
TI  - Wave propagation in one-dimensional optical quasiperiodic systems.
AB  - One-dimensional quasiperiodic optical systems are studied, using a Schrodinger
      like equation with a potential V(x)=2lambda(1) cos x+2lambda(2) cos alphax as an
      approximation to the wave equation in the slowly-varying wave approximation. It
      is shown that small changes in the parameter alpha produce major changes in the
      band structure of the system. For certain values of alpha, the band structure
      consists of many "thin bands" and allows the possibility of dense multiplexing.
      The propagation of "noisy optical waves" that contain many frequencies with a
      thermal distribution is also studied with a thermodynamic model. Quantities like
      the thermodynamically averaged group velocity and the thermodynamically averaged
      inverse effective mass are introduced in order to quantify the complex relation
      between the frequency and wave vector in these systems.

PMID- 11580467
TI  - Reflection and refraction of a transient temperature field at a plane interface
      using Cagniard-de Hoop approach.
AB  - An instantaneous line heat source located in the medium consisting of two half
      spaces with different thermal properties is considered. Green's functions for the
      temperature field are derived using the Laplace and Fourier transforms in time
      and space and their inverting by the Cagniard-de Hoop technique known in
      elastodynamics. The characteristic feature of the proposed approach consists in
      the application of the Cagniard-de Hoop method to the transient heat conduction
      problem. The idea is suggested by the fact that the Laplace transform in time
      reduces the heat conduction equation to a Helmholtz equation, as for the wave
      propagation. Derived solutions exhibit some wave properties. First, the
      temperature field is decomposed into the source field and the reflected field in
      one half-space and the transmitted field in the other. Second, the laws of
      reflection and refraction can be deduced for the rays of the temperature field.
      In this connection the ray concept is briefly discussed. It is shown that the
      rays, introduced in such a way that they are consistent with Snell's law do not
      represent the directions of heat flux in the medium. Numerical computations of
      the temperature field as well as diagrams of rays and streamlines of the
      temperature field are presented.

PMID- 11580468
TI  - Temporal development of photorefractive solitons up to telecommunication
      wavelengths in strontium-barium niobate waveguides.
AB  - We experimentally investigate the temporal development of photorefractive
      solitons in strontium-barium niobate waveguides at visible and infrared
      wavelengths. The development times in the infrared are shown to be comparable
      with those in the visible. The results are compared with predictions of a
      previously published model.

PMID- 11580469
TI  - Dispersion relation of guided-mode resonances and Bragg peaks in dielectric
      diffraction gratings.
AB  - We present the dispersion relation of guided-mode resonances in non-dissipative
      dielectric diffraction gratings, both for s-polarized (TE mode) and p-polarized
      (TM mode) incident waves. We present a simple approximate theory as well as a
      rigorous calculation within the so-called coupled-wave theory. We discuss the
      dependence of the positions and the lifetimes of the resonances on the thickness
      of the gratings and on the strength of its modulation. We find that the
      diffraction efficiency of the different orders show peaks at different Bragg
      orders.

PMID- 11580471
TI  - Theoretical analysis of acoustic stop bands in two-dimensional periodic
      scattering arrays.
AB  - This paper presents a theoretical analysis of the recently reported observation
      of acoustic stop bands in two-dimensional scattering arrays [Robertson and Rudy,
      J. Acoust. Soc. Am. 104, 694 (1998)]. A self-consistent wave scattering theory,
      incorporating all orders of multiple scattering, is used to obtain the wave
      transmission. The band structures for the regular arrays of cylinders are
      computed using the plane-wave expansion method. The theoretical results compare
      favorably with the experimental data.

PMID- 11580470
TI  - Effective nonlinear optical properties of metal-dielectric composite media with
      shape distribution.
AB  - The effective linear and nonlinear optical properties have been investigated in
      granular metal-dielectric composites taking the geometric shape of inclusions
      into account. Recently derived Maxwell-Garnett-type approximations are
      generalized to study the spectral function for composites in which the metal
      inclusions have a uniform distribution of geometric shapes. The numerical results
      show that the spectral density function becomes a prominent peak around small
      spectral value s within the non-self-consistent Maxwell-Garnett approximation but
      a broad continuous spectrum around large s besides the prominent peak around
      small s within the self-consistent Maxwell-Garnett approximation. Based on the
      spectral representation, we investigate the optical absorption and third-order
      nonlinear optical susceptibility. The results indicate that the shape
      distribution can lead to the separation of the nonlinearity enhancement peak from
      the absorption peak and thereby make the figure of merit more attractive.

PMID- 11580472
TI  - Bifurcation of gap solitons through catastrophe theory.
AB  - In the theory of optical gap solitons, slowly-moving finite-amplitude Lorentzian
      solutions are found to mediate the transition from bright to coexistent dark
      antidark solitary wave pairs when the laser frequency is detuned out of the
      proper edge of a dynamical photonic band gap. Catastrophe theory is applied to
      give a geometrical description of this strongly asymmetrical "morphing" process.

PMID- 11580473
TI  - Twisted Gaussian Schell-model solitons.
AB  - We show that a certain class of spatially partially coherent solitons, namely,
      twisted Gaussian Schell-model solitons, exists in a logarithmically saturable
      nonlinear medium with a noninstantaneous temporal response. Unlike previously
      reported Gaussian Schell-model solitons, those discussed here carry a position
      dependent twist phase, which vanishes in the fully coherent limit. We demonstrate
      that the presence of the twist phase provides an opportunity for controlling the
      degree of spatial coherence of such solitons without affecting their intensity.

PMID- 11580475
TI  - Lorentz-invariant superluminal tunneling.
AB  - It is shown that superluminal optical signaling is possible without violating
      Lorentz invariance and causality via tunneling through photonic band gaps in
      inhomogeneous dielectrics of a special kind.

PMID- 11580474
TI  - Parametric autoresonance.
AB  - We investigate parametric autoresonance: a persisting phase locking that occurs
      when the driving frequency of a parametrically excited nonlinear oscillator
      slowly varies with time. In this regime, the resonant excitation is continuous
      and unarrested by the oscillator nonlinearity. The system has three
      characteristic time scales, the fastest one corresponding to the natural
      frequency of the oscillator. We perform averaging over the fastest time scale and
      analyze the reduced set of equations analytically and numerically. Analytical
      results are obtained by exploiting the scale separation between the two remaining
      time scales that enables one to use the adiabatic invariant of the perturbed
      nonlinear motion.

PMID- 11580476
TI  - Optimization of the time-dependent traveling salesman problem with Monte Carlo
      methods.
AB  - A problem often considered in operations research and computational physics is
      the traveling salesman problem, in which a traveling salesperson has to find the
      shortest closed tour between a certain set of cities. This problem has been
      extended to more realistic scenarios, e.g., the "real" traveling salesperson has
      to take rush hours into consideration. We will show how this extended problem is
      treated with physical optimization algorithms. We will present results for a
      specific instance of Reinelt's library TSPLIB95, in which we define a zone with
      traffic jams in the afternoon.

PMID- 11580477
TI  - Supersonic motion of vacancies in a polyethylene crystal.
AB  - The possibility of supersonic motion of vacancies in a polyethylene crystal is
      revealed by means of analytical investigation and numerical simulation. It is
      demonstrated that in the crystalline field of immovable neighbors, a vacancy with
      a core size of about 70 CH2 groups and a velocity in the range of 1.02-1.05 sound
      velocity preserves itself for the time scale of about 1 ns. It is demonstrated
      that this type of structural defect is similar to coupled supersonic solitons
      described earlier in the one-dimensional chains with combined gradient and
      nongradient nonlinearity. An analytic approach is proposed for prediction of
      their shape and velocity. The simulation of the crystal with all degrees of
      freedom released demonstrates that the supersonic vacancy is still
      distinguishable. Its lifetime is less than 5 ps but still may be significant for
      physical applications.

PMID- 11580479
TI  - Multibox strategy for constructing highly accurate bound-state wave functions for
      three-body systems.
AB  - Variational, multibox approach is proposed to construct extremely accurate, bound
      state wave functions for arbitrary three-body systems. The high efficiency of our
      present approach is based on an optimal choice of nonlinear parameters in the
      exponential basis functions. The proposed method is very flexible, since the
      final wave function can also include a large number of separately optimized
      cluster fragments. The wave functions obtained are very compact and highly
      accurate. Such wave functions can be used to compute various bound state
      properties for different three-body systems. The proposed approach has been
      successfully tested on a large number of actual systems. It is shown that the
      present approach can be used to solve various three-body problems with, in
      principle, arbitrary precision. In particular, the long-standing problem of
      highly accurate determination of the weakly bound (1,1) states in the ddmu and
      dtmu muonic molecular ions has finally been solved. The determined binding
      energies are -1.974 988 088 0+/-5 x 10(-10) eV and -0.660 338 74+/-1 x 10(-8) eV,
      respectively.

PMID- 11580478
TI  - Taboo search by successive confinement: surveying a potential energy surface.
AB  - A taboo search for minima on a potential energy surface (PES) is performed by
      means of confinement molecular dynamics: the molecular dynamics trajectory of the
      system is successively confined to various basins on the PES that have not been
      sampled yet. The approach is illustrated for a 13-atom Lennard-Jones cluster. It
      is shown that the taboo search radically accelerates the process of surveying the
      PES, with the probability of finding a new minimum defined by a propagating Fermi
      like distribution.

PMID- 11580480
TI  - Stochastic model related to the Klein-Gordon equation.
AB  - In this note, a one-dimensional system composed of an assembly of interacting
      particles, is considered. Each particle in the assembly moves in a well-defined
      trajectory on a line with a velocity of fixed magnitude, which randomly reverses
      direction. The intrinsic forces in the system are assumed to induce stochastic
      transitions between velocity states in such a way that the average dynamics of
      the assembly is Newtonian. It is shown that there is a close analogy between
      collective oscillations in the model system and the propagation of a free quantum
      particle in one dimension.

PMID- 11580481
TI  - Controlling spatiotemporal chemical chaos using delayed feedback.
AB  - Control of chemical chaos in a spatially extended system mimicking CO oxidation
      on a Pt(110) single-crystal surface is achieved using delayed feedback
      techniques. For appropriate parameter values the uncontrolled model system
      exhibits both amplitude and phase turbulence. Superimposing a delayed feedback on
      the natural dynamics, suppression of spatiotemporal complexity is attained via
      stabilization of ordered states consisting of stable patterns.

PMID- 11580482
TI  - Delayed coupling of logistic maps.
AB  - We study the synchronization of logistic maps in a one-way coupling
      configuration. The master system is coupled to the slave system with a delay
      n(1), and the slave is a delayed logistic map with a delay n(2). We show that
      when the slave system has no delay (n(2)=0), perfectly synchronized solutions
      exist for strong enough coupling. In these solutions the slave variable y is
      retarded with respect to the master variable x with a retardation equal to the
      delay of the coupling [y(i+n(1))=x(i)]. When n(2) not equal 0, a regime of
      generalized synchronization is observed, where y(i+n(1)) is synchronized with
      x(i), but not completely, since the master and the slave systems obey different
      maps. We introduced a similarity function as an indicator of the degree of
      synchronization and, using a noisy master source, distinguished synchronization
      from noise-induced correlations.

PMID- 11580483
TI  - How does a periodic rotating wave emerge from high-dimensional chaos in a ring of
      coupled chaotic oscillators?
AB  - A route to typical rotating waves from high-dimensional chaos is investigated in
      diffusively coupled chaotic Rossler oscillators. By increasing the coupling from
      zero, a high-dimensional spatiotemporal chaos changes into a coherent state,
      which is periodic in time and well ordered in space, through consecutive
      transitions. A crossover transition from spatially random chaos to spatially
      ordered chaos with phase locking and orientational equality (for two directions)
      breaking is a crucial step for establishing the typical spatial order of the
      rotating wave.

PMID- 11580484
TI  - Superluminal pulse reflection in asymmetric one-dimensional photonic band gaps.
AB  - Superluminal pulse reflection is shown to occur in a class of one-dimensional
      asymmetric photonic band gaps in which a spectral window inside the gap is
      opened. By means of a coupled-mode equation analysis, we describe in detail two
      possible realizations of superluminal pulse reflection that can be achieved using
      fiber Bragg gratings. The former method is based on the introduction of a defect
      into the otherwise periodic dielectric structure, whereas the latter one exploits
      the interference of two closely-spaced resonance modes and simulates the
      dispersion properties of an inverted medium possessing a doublet line.

PMID- 11580485
TI  - Nonlinear parametric instability in double-well lattices.
AB  - A possibility of a nonlinear resonant instability of uniform oscillations in
      dynamical lattices with harmonic intersite coupling and onsite nonlinearity is
      predicted. Numerical simulations of a lattice with a double-well onsite
      anharmonic potential confirm the existence of the nonlinear instability with an
      anomalous value of the corresponding power index, approximately 1.57, which is
      intermediate between the values 1 and 2 characterizing the linear and nonlinear
      (quadratic) instabilities. The anomalous power index may be a result of a
      competition between the resonant quadratic instability and nonresonant linear
      instabilities. The observed instability triggers transition of the lattice into a
      chaotic dynamical state.

PMID- 11580486
TI  - Kink dynamics in a topological straight phi4 lattice.
AB  - Recently proposed was a discretization for nonlinear Klein-Gordon field theories
      in which the resulting lattice preserves the topological (Bogomol'nyi) lower
      bound on the kink energy and, as a consequence, has no Peierls-Nabarro barrier
      even for large spatial discretizations (h approximately 1.0). It was then
      suggested that these "topological discrete systems" are a natural choice for the
      numerical study of continuum kink dynamics. Giving particular emphasis to the
      straight phi(4) theory, we numerically investigate kink-antikink scattering and
      breather formation in these topological lattices. Our results indicate that, even
      though these systems are quite accurate for studying free kinks in coarse
      lattices, for legitimate dynamical kink problems the accuracy is rather
      restricted to fine lattices (h approximately 0.1). We suggest that this fact is
      related to the breaking of the Bogomol'nyi bound during the kink-antikink
      interaction, where the field profile loses its static property as required by the
      Bogomol'nyi argument. We conclude, therefore, that these lattices are not
      suitable for the study of more general kink dynamics, since a standard
      discretization is simpler and has effectively the same accuracy for such
      resolutions.

PMID- 11580487
TI  - Comment on "Mie scattering from a sonoluminescing bubble with high spatial and
      temporal resolution".
AB  - A key parameter underlying the existence of sonoluminescence (or SL) is the time
      dependence of the radius R(t) of the collapsing bubble from which SL originates.
      With regard to the use of light scattering to measure this quantity, we wish to
      note that we disagree with the statement of Gompf and Pecha-highly compressed
      water causes the minimum in scattered light to occur 700 ps before SL-and that
      this effect leads to an overestimate of the bubble wall velocity. We discuss
      potential artifacts in their experimental arrangement and reply to their
      criticisms of our experiments on Mie scattering.

PMID- 11580489
TI  - Critical temperature shift in weakly interacting Bose gas.
AB  - With a high-performance Monte Carlo algorithm we study the interaction-induced
      shift of the critical point in weakly interacting three-dimensional /psi/(4)
      theory (which includes quantum Bose gas). In terms of critical density, n(c),
      mass, m, interaction, U, and temperature, T, this shift is universal:
      Deltan(c)(T) = -Cm(3)T(2)U, the constant C found to be equal to 0.0140+/-0.0005.
      For quantum Bose gas with the scattering length a this implies DeltaT(c)/T(c) =
      C(0)an(1/3), with C(0) = 1.29+/-0.05.

PMID- 11580488
TI  - BEC transition temperature of a dilute homogeneous imperfect Bose gas.
AB  - The leading-order effect of interactions on a homogeneous Bose gas is
      theoretically predicted to shift the critical temperature by an amount DeltaT(c)
      approximately equal to ca(sc)n(1/3)T(0) from the ideal gas result T(0), where
      a(sc) is the scattering length, n is the density, and c is a pure number. There
      have been several different theoretical estimates for c. We claim to settle the
      issue by measuring the numerical coefficient in a lattice simulation of O(2)
      straight phi(4) field theory in three dimensions-an effective theory which, as
      observed previously in the literature, can be systematically matched to the
      dilute Bose gas problem to reproduce nonuniversal quantities such as the critical
      temperature. We find c = 1.32+/-0.02.

PMID- 11580490
TI  - Nonanalytic dependence of the transition temperature of the homogeneous dilute
      Bose gas on scattering length.
AB  - We show that the shift in the transition temperature of the dilute homogeneous
      Bose gas is nonanalytic in the scattering amplitude a. The first correction
      beyond the positive linear shift in a is negative and of order a(2)lna. This
      nonuniversal nonanalytic structure indicates how the discrepancies between
      numerical calculations at finite a can be reconciled with calculations of the
      limit a-->0, since the linearity is apparent only for anomalously small a.

PMID- 11580491
TI  - Casimir interaction among objects immersed in a fermionic environment.
AB  - Using ensembles of two, three, and four spheres immersed in a fermionic
      background we evaluate the (integrated) density of states and the Casimir energy.
      We thus infer that for sufficiently smooth objects, whose various geometric
      characteristic lengths are larger then the Fermi wave length one can use the
      simplest semiclassical approximation (the contribution due shortest periodic
      orbits only) to evaluate the Casimir energy. We also show that the Casimir energy
      for several objects can be represented fairly accurately as a sum of pairwise
      Casimir interactions between pairs of objects.

PMID- 11580493
TI  - Resonance superfluidity in a quantum degenerate Fermi gas.
AB  - We consider the superfluid phase transition that arises when a Feshbach resonance
      pairing occurs in a dilute Fermi gas. We apply our theory to consider a specific
      resonance in potassium ((40)K), and find that for achievable experimental
      conditions, the transition to a superfluid phase is possible at the high critical
      temperature of about 0.5T(F). Observation of superfluidity in this regime would
      provide the opportunity to experimentally study the crossover from the superfluid
      phase of weakly coupled fermions to the Bose-Einstein condensation of strongly
      bound composite bosons.

PMID- 11580492
TI  - Quantum phases of vortices in rotating Bose-Einstein condensates.
AB  - We investigate the ground states of weakly interacting bosons in a rotating trap
      as a function of the number of bosons, N, and the average number of vortices,
      N(V). We identify the filling fraction nu identical with N/N(V) as the parameter
      controlling the nature of these states. We present results indicating that, as a
      function of nu, there is a zero temperature phase transition between a triangular
      vortex lattice phase, and strongly correlated vortex liquid phases. The vortex
      liquid phases appear to be the Read-Rezayi parafermion states.

PMID- 11580494
TI  - Monopoles in an antiferromagnetic Bose-Einstein condensate.
AB  - We show that even in three dimensions an antiferromagnetic spin-1 Bose-Einstein
      condensate, which can, for instance, be created with (23)Na atoms in an optical
      trap, has not only singular linelike vortex excitations, but also allows for
      singular pointlike topological excitations, i.e., monopoles similar to the 't
      Hooft-Polyakov monopoles. We discuss the static and dynamic properties of these
      monopoles.

PMID- 11580495
TI  - Ruling out chaos in compact binary systems.
AB  - We investigate the orbits of compact binary systems during the final inspiral
      stage before coalescence by integrating the post-Newtonian equations of motion.
      We include spin-orbit and spin-spin coupling, which, according to a recent study
      [J. Levin, Phys. Rev. Lett. 84, 3515 (2000)], may cause the orbits to appear
      chaotic. To examine this claim, we calculate the divergence of nearby
      trajectories and attempt to measure the Lyapunov exponent gamma. For all systems
      considered, we find no chaotic behavior, placing a lower limit on the divergence
      time t(L) identical with 1/gamma that is many times greater than the typical
      inspiral time, suggesting that chaos should not adversely affect the detection of
      inspiral events.

PMID- 11580496
TI  - Initial data for two Kerr-like black holes.
AB  - We prove the existence of a family of initial data for the Einstein vacuum
      equation which can be interpreted as the data for two Kerr-like black holes in an
      arbitrary location and with spins pointing in arbitrary directions. We also
      provide a method to compute them. If the mass parameter of one of the black holes
      is zero, then this family reduces exactly to the Kerr initial data. The existence
      proof is based on a general property of the Kerr metric which can be used in
      other constructions as well. Further generalizations are also discussed.

PMID- 11580497
TI  - Plunge waveforms from inspiralling binary black holes.
AB  - We study the coalescence of nonspinning binary black holes from near the
      innermost stable circular orbit down to the final single rotating black hole. We
      use a technique that combines the full numerical approach to solve the Einstein
      equations, applied in the truly nonlinear regime, and linearized perturbation
      theory around the final distorted single black hole at later times. We compute
      the plunge waveforms, which present a non-negligible signal lasting for t
      approximately 100M showing early nonlinear ringing, and we obtain estimates for
      the total gravitational energy and angular momentum radiated.

PMID- 11580499
TI  - Production of a Higgs boson accompanied by two jets via gluon fusion.
AB  - Real-emission corrections to gg-->H, which lead to H+2 jet events, are calculated
      at order alpha(4)(s). Contributions include top-quark triangles, boxes, and
      pentagon diagrams and are evaluated analytically for arbitrary top mass m(t).
      This new source of H+2 jet events is compared to the weak-boson fusion cross
      section for a range of Higgs boson masses. The heavy top-mass approximation
      appears to work well for intermediate Higgs-boson masses, provided that the
      transverse momenta of the final-state partons are smaller than the top-quark
      mass.

PMID- 11580498
TI  - Dynamical initial conditions in quantum cosmology.
AB  - Loop quantum cosmology is shown to provide both the dynamical law and initial
      conditions for the wave function of a universe by one discrete evolution
      equation. Accompanied by the condition that semiclassical behavior is obtained at
      large volume, a unique wave function is predicted.

PMID- 11580501
TI  - Dipole excitation of alpha clusters in (6)Li and (7)Li.
AB  - Dipole excitations in highly excited energy regions of (6)He and (7)He nuclei
      were investigated via the ((7)Li,(7)Be) reaction with an incident energy of 65A
      MeV at forward scattering angles. The resonances at Q approximately equal to -30
      MeV observed commonly for both (6)Li and (7)Li targets were found to be excited
      via both spin-flip and spin-nonflip transitions with DeltaL = 1. Based on the
      observed excitation energy, width, and cross section of each resonance, the
      relevant resonances are inferred to be analogs of the dipole resonances of alpha
      clusters in the (6)Li and (7)Li nuclei.

PMID- 11580500
TI  - Coulomb energy differences in t = 1 mirror rotational bands in (50)Fe and (50)Cr.
AB  - Gamma rays from the N = Z-2 nucleus (50)Fe have been observed, establishing the
      rotational ground state band up to the state J(pi) = 11+ at 6.994 MeV excitation
      energy. The experimental Coulomb energy differences, obtained by comparison with
      the isobaric analog states in its mirror (50)Cr, confirm the qualitative
      interpretation of the backbending patterns in terms of successive alignments of
      proton and neutron pairs. A quantitative agreement with experiment has been
      achieved by exact shell model calculations, incorporating the differences in
      radii along the yrast bands, and properly renormalizing the Coulomb matrix
      elements in the pf model space.

PMID- 11580502
TI  - Complete measurement of S((1)D2) photofragment alignment from Abel-invertible ion
      images.
AB  - A novel method to measure directly the photofragment alignment from Abel
      invertible two-dimensional ion images, as a function of photofragment recoil
      velocity, is demonstrated for S(1D2) atoms from the photodissociation of carbonyl
      sulfide at 223 nm. The results are analyzed in terms of coherent and incoherent
      contributions from two dissociative states, showing that the phase differences of
      the asymptotic wave functions of the fast and slow recoil-velocity channel are
      approximately pi/2 and 0, respectively.

PMID- 11580503
TI  - Doppler cooling and trapping on forbidden transitions.
AB  - Ultracold atoms at temperatures close to the recoil limit have been achieved by
      extending Doppler cooling to forbidden transitions. A cloud of (40)Ca atoms has
      been cooled and trapped to a temperature as low as 6 microK by operating a
      magnetooptical trap on the spin-forbidden intercombination transition. Quenching
      the long-lived excited state with an additional laser enhanced the scattering
      rate by a factor of 15, while a high selectivity in velocity was preserved. With
      this method, more than 10% of precooled atoms from a standard magnetooptical trap
      have been transferred to the ultracold trap. Monte Carlo simulations of the
      cooling process are in good agreement with the experiments.

PMID- 11580504
TI  - Boundary conditions for the Pauli equation: application to photodetachment of Cs
      .
AB  - We formulate the boundary conditions near the atomic nucleus for solving the
      Pauli equation, based on the analytic solution of the Dirac equation for a
      Coulomb potential. We then integrate the Pauli equation using an effective
      potential that is adjusted to reproduce Dirac R-matrix scattering phase shifts,
      and find the (3)P(o)(1) resonance contribution to the photodetachment cross
      section of Cs-. Our photodetachment cross sections agree with recent experiments
      by Scheer et al. [Phys. Rev. Lett. 80, 684 (1998)] after tuning the resonance
      position by 2.4 meV. We also provide angle-differential photodetachment cross
      sections and the corresponding asymmetry parameter beta near the Cs(6s)
      threshold.

PMID- 11580505
TI  - Dynamical relativistic effects in photoionization: spin-orbit-resolved angular
      distributions of xenon 4d photoelectrons near the Cooper minimum.
AB  - Two decades ago, it was predicted [Y. S. Kim et al., Phys. Rev. Lett. 46, 1326
      (1981)] that relativistic effects should alter the dynamics of the
      photoionization process in the vicinity of Cooper minima. The present
      experimental and theoretical study of the angular distributions of Xe 4d(3/2) and
      4d(5/2) photoelectrons demonstrates this effect for the first time. The results
      clearly imply that relativistic effects are likely to be important for
      intermediate- Z atoms at most energies.

PMID- 11580507
TI  - Recoil momentum spectroscopy of highly charged ion collisions on magneto
      optically trapped Na.
AB  - We have used a cold ( T<<1 mK), laser-cooled target of Na atoms confined in a
      magneto-optical trap to study electron capture processes during highly charged
      ion-sodium atom collisions at keV energies. Momentum distributions of target ions
      were determined by employing time-of-flight and position sensitive detection of
      the Na ions, produced during the collisions and extracted by a weak electric
      field. In this way impact parameter sensitive information about multielectron
      capture processes is obtained.

PMID- 11580508
TI  - Kinematically complete charge exchange experiment in the Cs(+)+Rb collision
      system using a MOT target.
AB  - Charge exchange is examined with unprecedented precision using the newly
      developed magneto-optical trap-target recoil ion momentum spectroscopy (MOTRIMS)
      technique. Initial and final state selective, charge exchange cross sections are
      obtained for 6 keV Cs+ colliding with rubidium in 5s and 5p states. For each
      charge transfer channel, cross sections differential in scattering angle are
      measured. These data are used to overturn previous long-standing conjecture as to
      the origin of oscillations seen in total charge exchange cross section
      measurements, and compare well with an enhanced Demkov model calculation.

PMID- 11580506
TI  - Fraunhofer diffraction of atomic matter waves: electron transfer studies with a
      laser cooled target.
AB  - We have constructed an apparatus combining the experimental techniques of cold
      target recoil ion momentum spectroscopy and a laser cooled target. We measure
      angle differential cross sections in Li(+)+Na-->Li+Na(+) electron transfer
      collisions in the keV energy regime with a momentum resolution of 0.12 a.u.
      yielding an order of magnitude better angular resolution than previous
      measurements. We resolve Fraunhofer-type diffraction patterns in the differential
      cross sections. Good agreement with predictions of the semiclassical impact
      parameter method is obtained.

PMID- 11580509
TI  - Observation of a 1/t decay law for hot clusters and molecules in a storage ring.
AB  - The exponential law is valid both for decay from a single quantum state into a
      continuum and for an ensemble maintained in thermal equilibrium. For statistical
      decay of an ensemble of isolated systems with a broad energy distribution, the
      exponential decay is replaced by a 1/t distribution. We present confirmation of
      this decay law by experiments with cluster anions in a small electrostatic
      storage ring. Deviations from the 1/t law for such an ensemble give important
      information on the dynamics of the systems. As examples, we present measurements
      revealing strong radiative cooling of anions of both metal clusters and
      fullerenes.

PMID- 11580510
TI  - Squeezed light from spin-squeezed atoms.
AB  - We propose to transfer quantum correlations from atoms to light by Raman
      scattering of a strong laser pulse on a spin-squeezed atomic sample. We prove
      that the emission is restricted to a single field mode which perfectly inherits
      the quantum correlations of the atomic system.

PMID- 11580511
TI  - Role of entanglement in two-photon imaging.
AB  - The use of entangled photons in an imaging system can exhibit effects that cannot
      be mimicked by any other two-photon source, whatever the strength of the
      correlations between the two photons. We consider a two-photon imaging system in
      which one photon is used to probe a remote (transmissive or scattering) object,
      while the other serves as a reference. We discuss the role of entanglement versus
      correlation in such a setting, and demonstrate that entanglement is a
      prerequisite for achieving distributed quantum imaging.

PMID- 11580512
TI  - Nonlinear optics with less than one photon.
AB  - We demonstrate suppression and enhancement of spontaneous parametric down
      conversion via quantum interference with two weak fields from a local oscillator
      (LO). Effectively, pairs of LO photons up-convert with high efficiency for
      appropriate phase settings, exhibiting an effective nonlinearity enhanced by at
      least 10 orders of magnitude. This constitutes a two-photon switch and promises
      to be applicable to a wide variety of quantum nonlinear optical phenomena.

PMID- 11580513
TI  - Revivals and oscillations of the momentum of light in a planar multimode
      waveguide.
AB  - The evolution of the transverse momentum of monochromatic light entering a
      multimode planar waveguide at large angle is investigated. We report on
      oscillations of the momentum caused by the beatings between the adjacent
      populated modes of the waveguide and their periodic collapses and revivals. A new
      type of an interferometer based on this effect with fringe spacing as small as
      lambda/9 is demonstrated experimentally, and periods as small as lambda/1000 seem
      to be feasible.

PMID- 11580514
TI  - Computational aberration correction for an arbitrary linear imaging system.
AB  - We show that aberration corrections can be made in any arbitrary linear imaging
      system provided the aberrations are well characterized and at least one of these
      aberrations can be independently varied in a well-controlled manner. We derive a
      generalization of the Schrodinger equation for wave propagation in aberration
      space assuming forward scattering. Transport equations in aberration space are
      derived. A general iterative algorithm which can retrieve the phase, and is
      robust in the presence of noise, is also derived. This is demonstrated using
      simulated data pertinent to electron microscopy, from a series of images with
      differing spherical aberration.

PMID- 11580515
TI  - Nonstationary time-series analysis: accurate reconstruction of driving forces.
AB  - We propose a simple method for the accurate reconstruction of slowly changing
      external forces acting on nonlinear dynamical systems. The method traces the
      evolution of the external force by locally linearizing the map dependency with
      the shifting parameter. Application of our algorithm to synthetic data
      corresponding to discrete models of evolving ecosystems shows an accuracy that
      outperforms those of previous methods in the literature. In addition, an
      application to the real-world sunspot time series recovers recently reported
      changes in solar activity during the last century.

PMID- 11580516
TI  - Inverse statistics of smooth signals: the case of two dimensional turbulence.
AB  - The problem of inverse statistics (statistics of distances for which the signal
      fluctuations are larger than a certain threshold) in differentiable signals with
      power law spectrum, E(k) approximately k(-alpha), 3< or =alpha<5, is discussed.
      We show that for these signals, with random phases, exit-distance moments follow
      a bifractal distribution. We also investigate two dimensional turbulent flows in
      the direct cascade regime, which display a more complex behavior. We give
      numerical evidences that the inverse statistics of 2D turbulent flows is
      described by a multifractal probability distribution; i.e., the statistics of
      laminar events is not simply captured by the exponent alpha characterizing the
      spectrum.

PMID- 11580518
TI  - Pressure-induced quenching of the Jahn-Teller distortion and insulator-to-metal
      transition in LaMnO(3).
AB  - LaMnO(3) was studied by synchrotron x-ray diffraction, optical spectroscopies,
      and transport measurements under pressures up to 40 GPa. The cooperative Jahn
      Teller (JT) distortion is continuously reduced with increasing pressure. There is
      strong indication that the JT effect and the concomitant orbital order are
      completely suppressed above 18 GPa. The system, however, retains its insulating
      state to approximately 32 GPa, where it undergoes a bandwidth-driven insulator
      metal transition. Delocalization of electron states, which suppresses the JT
      effect but is insufficient to make the system metallic, appears to be a key
      feature of LaMnO(3) at 20-30 GPa.

PMID- 11580517
TI  - Experimental determination of critical threshold in electron transport on Tore
      Supra.
AB  - In Tore Supra plasmas with fast wave electron heating, a critical threshold in
      the electron temperature gradient (inverted DeltaT(e)) is clearly observed, i.e.,
      a finite value of inverted DeltaT(e) for which the turbulent heat diffusivity
      vanishes. The radial profile of this critical gradient is experimentally
      determined from a set of discharges characterized by similar plasma parameters
      with fast wave powers ranging from 0.75 to 7.4 MW. The dependence of the electron
      heat flux on the gradient length is found to be offset linearly. The offset term
      increases linearly with the ratio of the local magnetic shear to the safety
      factor.

PMID- 11580519
TI  - Smallest nanotube: breaking the symmetry of sp(3) bonds in tubular geometries.
AB  - We describe how sp(2) carbon, threefold coordinated by other carbons, can be
      replaced by sp(3) carbon, also threefold carbon coordinated, to produce extremely
      small-diameter ( approximately 0.4 nm) carbon nanowires with only minimal bond
      angle distortion. Under a naming convention analogous to that for ordinary carbon
      nanotubes, the smallest sp(3) tubes have wrapping indices (3,0) and (2,2). These
      systems have large band gaps and a stiffness larger even than that of traditional
      sp(2)-bonded carbon nanotubes. They therefore form the stiffest one-dimensional
      systems known.

PMID- 11580520
TI  - Roughness of crack interfaces in two-dimensional beam lattices.
AB  - The roughness of crack interfaces is reported in quasistatic fracture, using an
      elastic network of beams with random breaking thresholds. For strong disorders we
      obtain zeta = 0.86(3) for the roughness exponent, a result which is very
      different from the minimum energy surface exponent, i.e., zeta = 2 / 3. A
      crossover to lower values is observed as the disorder is reduced, the exponent in
      this regime being strongly dependent on the disorder.

PMID- 11580521
TI  - Bonse-Hart angular profiles realized for multiply Bragg reflected neutrons.
AB  - We have produced a monochromatic neutron beam with the sharpest angular profile
      to date. Multiple Bragg reflections from optimally designed channel-cut silicon
      single crystals have produced neutron beams with theoretical Darwin angular
      profiles. This experiment constitutes the first realization of the proposal made
      by Bonse and Hart 35 years ago and opens up avenues for ultrasmall angle neutron
      scattering studies down to wave vector transfers of 10(-5) A(-1).

PMID- 11580522
TI  - Effects of surface roughness on self- and transport diffusion in porous media in
      the Knudsen regime.
AB  - The effect of surface roughness on Knudsen diffusion in nanoporous media is
      investigated by means of dynamic Monte Carlo simulations in three-dimensional
      rough fractal pores. These simulations yield new insight and explain a number of
      apparent inconsistencies by revealing a striking difference between the roughness
      dependence of transport diffusion and gradientless (self- or tracer) diffusion.
      Both analytical and simulation results show a significant roughness dependence of
      self-diffusion in the Knudsen regime. Transport diffusion, on the other hand, is
      roughness independent, as the fluxes do not depend on the detailed residence time
      and molecular trajectories.

PMID- 11580523
TI  - Anisotropic interactions of hydrogen molecules from the pressure dependence of
      the rotational spectrum in the Ar(H2)(2) compound.
AB  - We report the pressure evolution, up to 70 GPa, of the fine structure of the
      S0(0) rotational excitation in the high-pressure Ar(H(2))(2) compound (with
      almost 100% para-H(2)) at about 30 K. A perturbative theoretical analysis is
      developed to calculate intensities and frequency shifts of the active Raman
      rotational components, on the basis of the intermolecular anisotropic
      interaction. The comparison between experimental results up to 35 GPa and
      calculation allows a reliable determination of the anisotropic intermolecular
      potential in the solid, both for H(2)-H(2) and H(2)-Ar at short range. Such
      results are important for the interpretation of the high-pressure orientational
      properties of solid hydrogen.

PMID- 11580524
TI  - Binary separation in very thin nematic films: thickness and phase coexistence.
AB  - The behavior as a function of temperature of very thin films (10 to 200 nm) of
      pentylcyanobiphenyl on silicon substrates is reported. In the vicinity of the
      nematic-isotropic transition we observe a coexistence of two regions of different
      thicknesses: thick regions are in the nematic state while thin ones are in the
      isotropic state. Moreover, the transition temperature is shifted downward
      following a 1/h(2) law ( h is the film thickness). Microscope observations and
      small-angle x-ray scattering allowed us to draw a phase diagram which is
      explained in terms of a binary first-order phase transition where thickness plays
      the role of an order parameter.

PMID- 11580525
TI  - Anisotropic scaling and generalized conformal invariance at Lifshitz points.
AB  - The behaviour of the 3D axial next-nearest-neighbor Ising model at the uniaxial
      Lifshitz point is studied using Monte Carlo techniques. A new variant of the
      Wolff cluster algorithm permits the analysis of systems far larger than in
      previous studies. The Lifshitz point critical exponents are alpha = 0.18(2), beta
      = 0.238(5), and gamma = 1.36(3). Data for the spin-spin correlation function are
      shown to be consistent with the explicit scaling function derived from the
      assumption of local scale invariance, which is a generalization of conformal
      invariance to the anisotropic scaling at the Lifshitz point.

PMID- 11580526
TI  - Hexatic order and surface ripples in spherical geometries.
AB  - In flat geometries, two-dimensional hexatic order has only a minor effect on
      capillary waves on a liquid substrate and on undulation modes in lipid bilayers.
      However, extended bond-orientational order alters the long-wavelength spectrum of
      these ripples in spherical geometries. We calculate this frequency shift and
      suggest that it might be detectable in lipid bilayer vesicles, at the surface of
      liquid metals, and in multielectron bubbles in liquid helium at low temperatures.
      Hexatic order also leads to a shift in the threshold for the fission instability
      induced in the later two systems by an excess of electric charge.

PMID- 11580527
TI  - Ge self-diffusion in epitaxial Si(1)-(x)Ge(x) layers.
AB  - Diffusion coefficients and activation energies have been determined for Ge
      diffusion in strain-relaxed Si(1)-(x)Ge(x) with x = 0.00, 0.10, 0.20, 0.30, 0.40,
      and 0.50. The activation energy drops from 4.7 eV in Si and Si(0.90)Ge(0.10) to
      3.2 eV at x = 0.50. This value compares with the literature value for Ge self
      diffusion in Ge, suggesting Ge-like diffusion already at x approximately equal to
      0.5. The effect of strain on the diffusion was also studied showing a decrease in
      diffusion coefficient and an increase in activation energy upon going from
      compressive over relaxed to tensile strain.

PMID- 11580529
TI  - Adsorption-induced step formation.
AB  - Through an interplay between density functional calculations, Monte Carlo
      simulations and scanning tunneling microscopy experiments, we show that an
      intermediate coverage of CO on the Pt(110) surface gives rise to a new rough
      equilibrium structure with more than 50% step atoms. CO is shown to bind so
      strongly to low-coordinated Pt atoms that it can break Pt-Pt bonds and
      spontaneously form steps on the surface. It is argued that adsorption-induced
      step formation may be a general effect, in particular at high gas pressures and
      temperatures.

PMID- 11580528
TI  - Closing the gap between experiment and theory: crystal growth by temperature
      accelerated dynamics.
AB  - We present atomistic simulations of crystal growth where realistic experimental
      deposition rates are reproduced, without needing any a priori information on the
      relevant diffusion processes. Using the temperature accelerated dynamics method,
      we simulate the deposition of 4 monolayers (ML) of Ag/Ag(100) at the rate of
      0.075 ML/s, thus obtaining a boost of several orders of magnitude with respect to
      ordinary molecular dynamics. In the temperature range analyzed (0-70 K), steering
      and activated mechanisms compete in determining the surface roughness.

PMID- 11580530
TI  - Self-assembly of two-dimensional islands via strain-mediated coarsening.
AB  - We demonstrate two distinctive effects of strain-induced island-island
      interaction on island size and spatial distribution during coarsening of 2D
      islands. When coarsening proceeds via only mass transport between islands, the
      interaction broadens the island size distribution, leading to a power-law
      dependence of island size uniformity on island number density. When coarsening
      proceeds via island migration in addition to mass transport between islands, the
      interaction can effectively direct island motion through island edge diffusion,
      leading to self-organized formation of a regular array of islands with both
      uniform size and spacing.

PMID- 11580531
TI  - Negative resistance and local charge-density-wave dynamics.
AB  - Charge-density-wave (CDW) dynamics is studied on a submicron length scale in
      NbSe(3) and o-TaS(3). Regions of negative absolute resistance are observed in the
      CDW sliding regime at sufficiently low temperatures. The origin of the negative
      resistance is attributed to the different forces that the deformed CDW and
      quasiparticles feel: the force on the CDW is merely caused by a difference of the
      electric potentials, while the quasiparticle current is governed by a difference
      of the electrochemical potentials.

PMID- 11580532
TI  - Exact results for the crossover from Gaussian to non-Gaussian order parameter
      fluctuations in quasi-one-dimensional electronic systems.
AB  - The physics of quasi-one-dimensional Peierls systems is dominated by order
      parameter fluctuations. We present an algorithm which allows us for the first
      time to exactly calculate physical properties of the electrons gas coupled to
      classical order parameter fluctuations. The whole range from the Gaussian regime
      dominated by amplitude fluctuations to the non-Gaussian regime dominated by phase
      fluctuations is accessible. Our results provide insight into the "pseudogap"
      phenomenon occurring in underdoped high- T(c) superconductors, quasi-one
      dimensional organic conductors, and liquid metals.

PMID- 11580533
TI  - Polarity inversion in polar-nonpolar-polar heterostructures.
AB  - We have observed an epilayer-thickness-dependent polarity inversion for the
      growth of CdTe on Sb(Bi)/CdTe(111)B. For films with Sb(Bi) thicknesses of less
      than 40 A (15 A), the CdTe layer shows a B (Te-terminated) face, but it switches
      to an A (Cd-terminated) face for thicker layers. On the other hand, a CdTe layer
      grown on Bi(Sb)/CdTe(111)A always shows the A face regardless of Sb or Bi layer
      thicknesses. In order to address the observations we have performed ab initio
      calculations, which suggest that the polarity of a polar material on a nonpolar
      one results from the binding energy difference between the two possible surface
      configurations.

PMID- 11580534
TI  - Nature of charge carriers in disordered molecular solids: are polarons compatible
      with observations?
AB  - Polaronic theories for charge transport in disordered organic solids,
      particularly molecularly doped polymers, have been plagued by issues of internal
      consistency related to the magnitude of physical parameters. We present a natural
      resolution of the problem by showing that, in the presence of correlated
      disorder, polaronic carriers with binding energies Delta approximately 50-500 meV
      and transfer integrals J approximately 1-20 meV are completely consistent with
      the magnitudes of field and temperature dependent mobilities observed.

PMID- 11580535
TI  - Quantum loop current in a C(60) molecular bridge.
AB  - The existence of a quantum loop current in a C(60) molecular bridge is predicted
      using the Green's function method. The model for the molecular bridge consists of
      a C(60) molecule attached to one-dimensional conductive electrodes. It is shown
      that the loop current is related to the degeneracy of the energy levels of the
      C(60) molecule. Specific to this loop current is its magnitude which is much
      larger than that of the source-drain current. The associated magnetic moment also
      shows certain remarkable features such as its inversion with the energy across
      the molecular levels and the restriction of its direction onto a single plane.

PMID- 11580536
TI  - Metallic behavior in dilute two-dimensional hole systems.
AB  - We have studied the metallic behavior in low-density two-dimensional p-GaAs
      systems, close to the apparent metal-insulator transition. Two observations are
      made concerning the origins of the metallic-like behavior. Within a given sample
      the strength of the metallic behavior is almost independent of the asymmetry of
      the confining potential, and is predominantly determined by the low-temperature
      resistivity (i.e., by k(F)l). In all our samples we find that at low densities,
      close to the transition from insulating to metallic behavior, the fractional
      decrease in conductivity with increasing temperature scales as T/T(F).

PMID- 11580538
TI  - Coulomb blockade of tunneling between disordered conductors.
AB  - We determine the zero-bias anomaly of the conductance of tunnel junctions by an
      approach unifying the conventional Coulomb blockade theory for ultrasmall
      junctions with the diffusive anomalies in disordered conductors. Both electron
      electron interactions within the electrodes and electron-hole interactions
      between the electrodes are taken into account nonperturbatively. Explicit results
      are given for one- and two-dimensional junctions, and the crossover to ultrasmall
      junctions is discussed.

PMID- 11580539
TI  - Quasiclassical negative magnetoresistance of a 2D electron gas: interplay of
      strong scatterers and smooth disorder.
AB  - We study the quasiclassical magnetotransport of noninteracting fermions in two
      dimensions moving in a random array of strong scatterers (antidots, impurities,
      or defects) on the background of a smooth random potential. We demonstrate that
      the combination of the two types of disorder induces a novel mechanism leading to
      a strong negative magnetoresistance, followed by the saturation of the
      magnetoresistivity rho(xx)(B) at a value determined solely by the smooth
      disorder. Experimental relevance to the transport in semiconductor
      heterostructures is discussed.

PMID- 11580537
TI  - Anisotropic disorder in high-mobility 2D heterostructures and its correlation to
      electron transport.
AB  - Surface morphology of high-mobility heterostructures is examined and correlated
      with dc transport. All samples examined show evidence of lines in the [11-0]
      direction with roughness ranging from small-amplitude features to severe
      anisotropic ridges. Transport in these samples is consistent with that in samples
      having artificially induced 1D charge modulations. The native surface properties
      reflect a prevalent, anisotropic disorder affecting 2D electron conduction.
      Importantly, the native lines are orthogonal to the stripes theoretically
      proposed to explain high Landau level transport anisotropies.

PMID- 11580540
TI  - Evidence for strong-coupling s-wave superconductivity in MgB2: (11)B NMR Study.
AB  - We have investigated a gap structure in a newly discovered superconductor, MgB2,
      through measurement of the (11)B nuclear spin-lattice relaxation rate,
      (11)(1/T(1)). (11)(1/T(1)) is proportional to the temperature (T) in the normal
      state, and decreases exponentially in the superconducting (SC) state, revealing a
      tiny coherence peak just below T(c). The T dependence of 1/T(1) in the SC state
      can be accounted for by an s-wave SC model with a large gap size of
      2Delta/k(B)T(c) approximately 5 which suggests it is in a strong-coupling regime.

PMID- 11580542
TI  - Strong enhancement of superconducting T(c) in ferromagnetic phases.
AB  - It is shown that the critical temperature for spin-triplet, p-wave
      superconductivity mediated by spin fluctuations is generically much higher in a
      Heisenberg ferromagnetic phase than in a paramagnetic one, due to the coupling of
      the magnons to the longitudinal magnetic susceptibility. Together with the
      tendency of the low-temperature ferromagnetic transition in very clean Heisenberg
      magnets to be of first order, this qualitatively explains the phase diagram
      recently observed in UGe(2).

PMID- 11580541
TI  - Observation of two-magnon bound states in the two-leg ladders of
      (Ca,La)(14)Cu(24)O(41).
AB  - Phonon-assisted two-magnon absorption is studied in the spin- 1/2 two-leg ladders
      of (Ca,La)(14)Cu(24)O(41) for E parallel c (legs) and E parallel a (rungs). We
      verify the theoretically predicted existence of two-magnon singlet bound states,
      which give rise to peaks at approximately equal to 2140 and 2800 cm(-1). The two
      magnon continuum is observed at approximately equal to 4000 cm(-1). Two different
      theoretical approaches (Jordan-Wigner fermions and perturbation theory) describe
      the data very well for J parallel approximately equal to 1020-1100 cm(-1), J
      parallel/J perpendicular approximately equal to 1-1.2. At high energies, the
      magnetic contribution to sigma(omega) is strikingly similar in the ladders and in
      the undoped high-T(c) cuprates, which emphasizes the importance of strong quantum
      fluctuations in the latter.

PMID- 11580543
TI  - Critical state theory for nonparallel flux line lattices in type-II
      superconductors.
AB  - Field penetration profiles in type-II superconductors with nonparallel vortex
      configurations are obtained by a proposed least action principle. We introduce a
      functional C[H-->] which is minimized for the current density constrained by J-
      >inDelta(H-->,x-->), where Delta is a bounded set. Within the isotropic case /J-
      >/< or =J(c)(H), the profiles H-->(x-->,t) are derived for an applied changing
      excitation. The model can reproduce the physical phenomena of flux transport and
      consumption, and the magnetization collapse in crossed field measurements.

PMID- 11580544
TI  - Loss of superconducting phase coherence in YBa(2)Cu(3)O(7) films: vortex-loop
      unbinding and Kosterlitz-Thouless phenomena.
AB  - The linear conductance G' + iG(") parallel to the CuO(2) planes of flat d = 50
      600 nm thin films is measured between 30 mHz and 800 kHz. The decay of the phase
      coherent superfluid density signals the proliferation of 3D vortex loops which
      terminates at T*<T(c), where omegaG"(T*) attains 35(5) nH(-1) being independent
      of d. We ascribe this novel transition to the blowout of loops which reach the
      film thickness. Above T(c), G(omega) appears to be determined by unbound vortex
      lines thermally excited in a 2D phase-incoherent superfluid showing features
      previously being associated with a Kosterlitz-Thouless transition.

PMID- 11580545
TI  - Parity-forbidden excitations of Sr(2)CuO(2)Cl(2) revealed by optical third
      harmonic spectroscopy.
AB  - We present the first study of nonlinear optical third-harmonic generation (THG)
      in the strongly correlated charge-transfer insulator Sr(2)CuO(2)Cl(2). For
      fundamental excitation in the near infrared, the THG spectrum reveals a strongly
      resonant response for photon energies near 0.7 eV. Polarization analysis reveals
      this novel resonance to be only partially accounted for by three-photon
      excitation to the optical charge-transfer exciton, and indicates that an even
      parity state at 2 eV, with a(1g) symmetry, participates in the third-harmonic
      susceptibility.

PMID- 11580546
TI  - Atomic-scale magnetic domain walls in quasi-one-dimensional Fe nanostripes.
AB  - Fe nanostripes on W(110) are investigated by Kerr magnetometry and spin-polarized
      scanning tunneling microscopy (SP-STM). An Arrhenius law is observed for the
      temperature dependent magnetic susceptibility indicating a one-dimensional
      magnetic behavior. The activation energy for creating antiparallel spin blocks
      indicates extremely narrow domain walls with a width on a length scale of the
      lattice constant. This is confirmed by imaging the domain wall by SP-STM. This
      information allows the quantification of the exchange stiffness and the
      anisotropy constant.

PMID- 11580547
TI  - Zero-magnetization ferromagnet proven by helicity-switching Compton scattering.
AB  - A single crystal of gadolinium-doped SmAl(2) has zero magnetization in the midst
      of the ordered temperature region, despite the probable ferromagnetic spin
      ordering. The asymmetry in Compton-scattering intensity when switching between
      right- and left-handed polarization of incident 150-keV synchrotron radiation
      provides decisive proof that ferromagnetic order is really there, and that spin
      and orbital magnetic contributions cancel. The experiments also show that the
      spin direction at this zero-magnetization state is rather stable against the
      external magnetic field and, nevertheless, reversible by a preceding control of
      temperature and an external field.

PMID- 11580548
TI  - Two-stage spin-flop transitions in the S = 1/2 antiferromagnetic spin chain
      BaCu(2)Si(2)O(7).
AB  - Two-stage spin-flop transitions are observed in the quasi-one-dimensional
      antiferromagnet BaCu(2)Si(2)O(7). A magnetic field applied along the easy axis
      induces a spin-flop transition at 2.0 T followed by a second transition at 4.9 T.
      The magnetic susceptibility indicates the presence of Dzyaloshinskii-Moriya (DM)
      antisymmetric interactions between the intrachain neighboring spins. We discuss a
      possible mechanism whereby the geometrical competition between DM and interchain
      interactions, as discussed for the two-dimensional antiferromagnet La(2)CuO(4),
      causes the two-stage spin-flop transitions.

PMID- 11580550
TI  - Non-Gaussian noise in quantum spin glasses and interacting two-level systems.
AB  - We study a general model for non-Gaussian 1/f noise based on an infinite range
      quantum Ising spin system in the paramagnetic state, or, equivalently,
      interacting two-level classical fluctuators. We identify a dilatation interaction
      term in the dynamics which survives the thermodynamic limit and circumvents the
      central limit theorem to produce non-Gaussian noise even when the equilibrium
      distribution is that of noninteracting spins. The resulting second spectrum
      ("noise of the noise") itself has a universal 1/f form which we analyze within a
      dynamical mean-field approximation.

PMID- 11580549
TI  - High resolution study of permanent photoinduced reflectivity changes and charge
      order domain switching in Bi(0.3)Ca(0.7)MnO(3).
AB  - We report near-field and far-field optical microscopic studies of photoinduced
      effects in charge-ordered Bi(0.3)Ca(0.7)MnO(3). Unlike previously reported
      transient photoinduced effects in manganites, we have observed permanent
      reflectivity changes following local sample illumination with 488 nm light. High
      resolution images of exposed regions reveal optical contrast on a submicrometer
      scale. This observation indicates that photonic band-gap structures may be
      created using holographic recording in manganites. We also present images of
      photoinduced charge-order domain switching in Bi(0.3)Ca(0.7)MnO(3).

PMID- 11580551
TI  - Ultraslow polaron dynamics in low-doped manganites from (139)La NMR-NQR and muon
      spin rotation.
AB  - We report a (139)La NMR investigation of low-doped insulating manganite samples
      (LaMnO(3+delta) and La(1-y)Ca(y)MnO(3+delta)) as a function of temperature. A
      volume fraction with fast nuclear relaxations was revealed by the inhomogeneous
      loss of the NMR signal over a broad temperature interval. Comparison with muon
      spin rotation data demonstrates that the wipeout of the (139)La signal is mainly
      due to slowly fluctuating electric field gradients. This provides strong evidence
      for the slow diffusion of lattice excitations, identified with Jahn-Teller small
      polarons.

PMID- 11580552
TI  - High-temperature electron paramagnetic resonance in magnets with the
      Dzyaloshinskii-Moriya interaction.
AB  - We analyze the high-temperature electron paramagnetic resonance (EPR) absorption
      in a weakly anisotropic Heisenberg magnet having two distinct types of
      anisotropy, represented, respectively, by a symmetric term and the Dzyaloshinskii
      Moriya (DM) term. Contrary to the widespread opinion that the latter is
      responsible for the excessive linewidth observed in the EPR spectra of many
      oxides, we prove that its contribution to the linewidth is only of the same level
      as that of the symmetric anisotropy. This gives a solution to the long-standing
      controversial problem of the high-temperature magnetic relaxation in quantum-spin
      systems with the DM interaction.

PMID- 11580553
TI  - Rigorous results for a hierarchy of generalized Heisenberg models.
AB  - The Lieb-Schultz-Mattis theorem is extended to generalized Heisenberg models
      related to unexceptional Lie algebras. It is shown that there are no energy gaps
      above the ground states for SO(4), Sp(2), and SU(4) Heisenberg models; but gaps
      are suspected to occur in SO(5) and SO(6) models. The nondegenerate ground state
      for these models is rigorously proven.

PMID- 11580554
TI  - Exact solutions for diluted spin glasses and optimization problems.
AB  - We study the low temperature properties of p-spin glass models with finite
      connectivity and of some optimization problems. Using a one-step functional
      replica symmetry breaking ansatz we can solve exactly the saddle-point equations
      for graphs with uniform connectivity. The resulting ground state energy is in
      perfect agreement with numerical simulations. For fluctuating connectivity
      graphs, the same ansatz can be used in a variational way: For p-spin models
      (known as p-XOR-SAT in computer science) it provides the exact configurational
      entropy together with the dynamical and static critical connectivities (for p =
      3, gamma(d) = 0.818, and gamma(s) = 0.918), whereas for hard optimization
      problems like 3-SAT or Bicoloring it provides new upper bounds for their critical
      thresholds ( gamma(var)(c) = 4.396 and gamma(var)(c) = 2.149).

PMID- 11580555
TI  - Polarized absorption spectra of single-walled 4 A carbon nanotubes aligned in
      channels of an AlPO(4)-5 single crystal.
AB  - We report the polarized optical absorption spectra of single-walled 4 A carbon
      nanotubes arrayed in the channels of an AlPO (4)-5 single crystal. When the light
      electric field (E) is polarized parallel to the tube direction (c), the spectra
      display a sharp peak at 1.37 eV, with two broadbands at 2.1 and 3.1 eV. In the E
      perpendicular c configuration, the tube is nearly transparent in the measured
      energy region 0.5-4.1 eV. The optical dipole selection rules are discussed, and
      the absorption bands are assigned to the dipole transitions between the Van Hove
      singularities. The measured absorption spectra agreed well with the ab initio
      calculations of band structure based on the local density function approximation.

PMID- 11580556
TI  - Magnetotransverse scattering of surface plasmon polaritons.
AB  - We show experimentally that the in-plane scattering of surface plasmon polaritons
      (SPP) is influenced by a perpendicular magnetic field. The average SPP flux is
      deflected into the direction perpendicular to both its initial propagation
      direction and the magnetic field direction. From a phenomenological point of
      view, this is an analogy to the Hall effect for electrons and a 2D equivalent of
      the photonic Hall effect.

PMID- 11580557
TI  - Parametric polariton amplification in semiconductor microcavities.
AB  - We present novel experimental results demonstrating the coherence properties of
      the nonlinear emission from semiconductor microcavities in the strong coupling
      regime, recently interpreted by parametric polariton four-wave mixing. We use a
      geometry corresponding to degenerate four-wave mixing. In addition to the
      predicted threshold dependence of the emission on the pump power and spectral
      blueshift, we observe a phase dependence of the amplification which is a
      signature of a coherent polariton wave mixing process.

PMID- 11580558
TI  - Surface temperature dependence of rotational excitation of H(2) scattered from
      Pd(111).
AB  - Classical dynamics simulations are performed to study rotational excitation of
      H(2) scattered from Pd(111), taking into account energy exchange with surface
      phonons through a 3D surface oscillator model. We show that dynamic trapping,
      identified recently in the study of dissociation dynamics, plays a prominent
      role. The corresponding long interaction time due to several recollisions allows
      an efficient energy exchange between H(2) molecules and surface phonons. This
      microscopic mechanism explains the puzzling experimental finding on the role of
      surface temperature in H(2)(nu = 0,J = 1-->3) excitation.

PMID- 11580559
TI  - Light-shift-induced quantum gates for ions in thermal motion.
AB  - An effective interaction between trapped ions in thermal motion can be generated
      by illuminating them simultaneously with a single laser resonant with the ionic
      carrier frequency. The ac Stark shift induces simultaneous "virtual" two-phonon
      transitions via several motional modes. Within a certain laser intensity range
      these transitions can interfere constructively, resulting in a relatively fast,
      heating-resistant two-qubit logic gate.

PMID- 11580560
TI  - Active fusion and fission processes on a fluid membrane.
AB  - We investigate the steady states and dynamical instabilities resulting from
      "particles" depositing on (fusion) and pinching off (fission) a fluid membrane.
      These particles could be either small lipid vesicles or isolated proteins. In the
      stable case, such fusion/fission events suppress long wavelength fluctuations of
      the membrane. In the unstable case, the membrane shoots out long tubular
      structures reminiscent of endosomal compartments or folded structures which bear
      a morphological resemblance to internal membranes of the cell.

PMID- 11580561
TI  - Emergence of taxis and synergy in angiogenesis.
AB  - Angiogenesis, the expansion of the vascular system feeding a tumor, is crucial to
      both primary tumors long-time growth and for the successful implantation of
      metastases. We formulate a model that relates the energetic requirements of the
      cancer cells to the production and diffusion of an angiogenic factor and to the
      ensuing evolution of neighboring endothelial cells. The model yields predictions
      for the development of neovascularization and for the increase in the blood flow
      to the tumor. We show that the directed growth of the vascular net is an emergent
      property and that therapies targeting different stages of the angiogenic process
      might have a synergistic effect.

PMID- 11580563
TI  - Comment on "Hole-burning experiments within glassy models with infinite range
      interactions".

PMID- 11580562
TI  - Comment on "Hole-burning experiments within glassy models with infinite range
      interactions".

PMID- 11580565
TI  - Comment on "Scaling of the conductivity with temperature and uniaxial stress in
      Si:B at the metal-insulator transition".

PMID- 11580567
TI  - Comment on "Low temperature magnetic instabilities in triply charged fulleride
      polymers".

PMID- 11580569
TI  - Comment on "Quantum clock synchronization based on shared prior entanglement".

PMID- 11580571
TI  - Absorption line shape of a one-dimensional Bose gas.
AB  - We discuss the line shape for an internal state transition for bosonic atoms
      confined as a one-dimensional gas, using a method by Haldane. Typical line shape
      is an edge singularity due to the absence of Bose-Einstein condensation in such
      systems.

PMID- 11580572
TI  - Realization of Bose-Einstein condensates in lower dimensions.
AB  - Bose-Einstein condensates of sodium atoms have been prepared in optical and
      magnetic traps in which the energy-level spacing in one or two dimensions exceeds
      the interaction energy between atoms, realizing condensates of lower
      dimensionality. The crossover into two-dimensional and one-dimensional
      condensates was observed by a change in aspect ratio and by the release energy
      converging to a nonzero value when the number of trapped atoms was reduced.

PMID- 11580573
TI  - Fate of the black string instability.
AB  - Gregory and Laflamme showed that certain nonextremal black strings (and p-branes)
      are unstable to linearized perturbations. It is widely believed that this
      instability will cause the black string horizon to classically pinch off and then
      quantum mechanically separate, resulting in higher dimensional black holes. We
      argue that this cannot happen. Under very mild assumptions, classical event
      horizons cannot pinch off. Instead, they settle down to new static black string
      solutions which are not translationally invariant along the string.

PMID- 11580574
TI  - Quantum energies of interfaces.
AB  - We present a method for computing the one-loop, renormalized quantum energies of
      symmetrical interfaces of arbitrary dimension and codimension using elementary
      scattering data. Internal consistency requires finite-energy sum rules relating
      phase shifts to bound state energies.

PMID- 11580575
TI  - Higgs sector radiative corrections and s-channel production.
AB  - Higgs boson mass sum rules of supersymmetric models offer attractive targets for
      precision tests at future muon colliders. These sum rules involve the gauge boson
      masses as well as the masses of the Higgs boson states which can be precisely
      measured in the s-channel production process at a muon collider. These
      measurements can sensitively probe radiative corrections to the Higgs boson
      masses as well as test for CP violation and nonminimality of the Higgs sector.

PMID- 11580578
TI  - Alignment delays in the N = Z nuclei (72)Kr, (76)Sr, and (80)Zr.
AB  - The ground state rotational bands of the N = Z nuclei (72)Kr, (76)Sr, and (80)Zr
      have been extended into the angular momentum region where rotation alignment of
      particles is normally expected. By measuring the moments of inertia of these
      bands we have observed a consistent increase in the rotational frequency required
      to start pair breaking, when compared to neighboring nuclei. (72)Kr shows the
      most marked effect. It has been widely suggested that these "delayed alignments"
      arise from np-pairing correlations. However, alignment frequencies are very
      sensitive to shape degrees of freedom and normal pairing, so the new experimental
      observations are still open to interpretation.

PMID- 11580579
TI  - Observation of (46)Cr and testing the isobaric multiplet mass equation at high
      spin.
AB  - The ground state band in (46)Cr and the isospin T = 1 band in (46)V have been
      delineated up to Ipi = 10(+) (tentatively 12(+)). These observations complete the
      highest spin T = 1 isospin triplet known. Following the isobaric multiplet mass
      equation, a combination of level energies in (46)Cr, (46)Ti, and (46)V are taken
      to highlight the angular momentum dependence of the isovector and isotensor parts
      of the interaction. The results are compared with full- fp-space shell model
      calculations. The influence of the one-body and two-body contributions to the
      isovector energy difference are investigated.

PMID- 11580577
TI  - First measurement of form factors of the decay Xi(0) --> Sigma(+)e(-)nu macro(e).
AB  - We present the first measurement of the form factor ratios g(1)/f(1) (direct
      axial vector to vector), g(2)/f(1) (second class current), and f(2)/f(1) (weak
      magnetism) for the decay Xi(0)-->Sigma(+)e(-)nu macro(e) using the KTeV (E799)
      beam line and detector at Fermilab. From the Sigma(+) polarization measured with
      the decay Sigma(+)-->p pi(0) and the e(-)-nu; correlation, we measure g(1)/f(1)
      to be 1.32+/-(0.21)(0.17)(stat)+/-0.05(syst), assuming the SU(3)(f) (flavor)
      values for g(2)/f(1) and f(2)/f(1). Our results are all consistent with exact
      SU(3)(f) symmetry.

PMID- 11580580
TI  - Crossing of shears bands in (197)Pb: B(M1) values and semiclassical description.
AB  - Subpicosecond lifetimes of states in shears band 1 in (197)Pb were measured by
      means of the recoil distance method employing Gammasphere and the New Yale
      Plunger Device. The extracted reduced matrix elements, B(M1), show a clear
      sensitivity to the crossing of different shears configurations reflecting the
      closing and reopening of the shears blades. The energies and B(M1) values in the
      band crossing region are successfully described in the framework of the
      semiclassical model of the shears bands. The relevance of core rotation
      contributions are shown. The results point to the existence of shears states with
      an angular momentum coupling angle larger than 90 degrees.

PMID- 11580582
TI  - Threshold effects on angular distributions for multiphoton detachment by intense
      elliptically polarized light.
AB  - Unusual threshold effects are found theoretically in the frequency and intensity
      dependence of angular distributions produced by an elliptically polarized laser
      as well as in the elliptic dichroism parameter, which measures the asymmetry of
      the angular distribution.

PMID- 11580583
TI  - Correlated electrons in lithiumlike hollow atoms.
AB  - We present a scheme for the explicit construction of highly correlated triply
      excited hollow states in Coulombic three-electron systems. Our analytical ansatz
      for the three-electron state is physically well justified and it produces
      configuration mixing coefficients in good agreement with data obtained from ab
      initio calculations.

PMID- 11580581
TI  - Production of (4)(double Lambda)H hypernuclei.
AB  - An experiment demonstrating the production of double-Lambda hypernuclei in (K(
      ),K(+)) reactions on (9)Be was carried out at the D6 line in the BNL alternating
      gradient synchrotron. The technique was the observation of pions produced in
      sequential mesonic weak decay, each pion associated with one unit of strangeness
      change. The results indicate the production of a significant number of the double
      hypernucleus (4)(double Lambda)H and the twin hypernuclei (4)(Lambda)H and
      (3)(Lambda)H. The relevant decay chains are discussed and a simple model of the
      production mechanism is presented. An implication of this experiment is that the
      existence of an S = -2 dibaryon more than a few MeV below the double Lambda mass
      is unlikely.

PMID- 11580584
TI  - Nuclear quadrupole moments of bismuth.
AB  - Multiconfiguration Dirac-Fock models have been employed to compute the electric
      field gradient in the ground state of the neutral bismuth atom. Combined with the
      experimental electric quadrupole hyperfine interaction constant, one obtains for
      (209)Bi the nuclear quadrupole moment Q = -516 (15) mb, which is almost 40% away
      from the previously accepted standard value [ -370 (26) mb], and narrows by over
      an order of magnitude the long-standing, extremely broad array of various results
      ranging from -370 to -710 mb. The recent Q values of (202-208,210(m)-213)Bi by
      Pearson et al. suffer a consequent change.

PMID- 11580585
TI  - Exact exchange-correlation treatment of dissociated H(2) in density functional
      theory.
AB  - Whereas the wave function of the dissociated H(2) molecule is easily obtained, an
      exact treatment of this system has not yet been given in density functional
      theory. We propose an orbital dependent exchange-correlation functional that
      yields this exact Kohn-Sham solution. This type of functional offers an
      alternative to local-density and generalized gradient approximations and the
      prospects are indicated for treating with it some outstanding problems in density
      functional theory.

PMID- 11580586
TI  - Radiation trapping in coherent media.
AB  - We show that the effective decay rate of Zeeman coherence, generated in a (87)Rb
      vapor by linearly polarized laser light, increases significantly with the atomic
      density. We explain this phenomenon as the result of radiation trapping. Our
      study shows that radiation trapping must be taken into account to fully
      understand many electromagnetically induced transparency experiments with
      optically thick media.

PMID- 11580587
TI  - Observation of image transfer and phase conjugation in stimulated down
      conversion.
AB  - We observe experimentally the transfer of angular spectrum and image formation in
      the process of stimulated parametric down-conversion. Images and interference
      patterns can be transferred from either the pump or the auxiliary laser beams to
      the stimulated down-converted one. The stimulated field propagates as the complex
      conjugate of the auxiliary laser. The phase conjugation is observed through
      intensity pattern measurements.

PMID- 11580588
TI  - Rabi oscillations of excitons in single quantum dots.
AB  - Transient nonlinear optical spectroscopy, performed on excitons confined to
      single GaAs quantum dots, shows oscillations that are analogous to Rabi
      oscillations in two-level atomic systems. This demonstration corresponds to a one
      qubit rotation in a single quantum dot which is important for proposals using
      quantum dot excitons for quantum computing. The dipole moment inferred from the
      data is consistent with that directly obtained from linear absorption studies.
      The measurement extends the artificial atom model of quantum dot excitonic
      transitions into the strong-field limit, and makes possible full coherent optical
      control of the quantum state of single excitons using optical pi pulses.

PMID- 11580589
TI  - Modulational instability in periodic quadratic nonlinear materials.
AB  - We investigate the modulational instability of plane waves in quadratic nonlinear
      materials with linear and nonlinear quasi-phase-matching gratings. Exact Floquet
      calculations, confirmed by numerical simulations, show that the periodicity can
      drastically alter the gain spectrum but never completely removes the instability.
      The low-frequency part of the gain spectrum is accurately predicted by an
      averaged theory and disappears for certain gratings. The high-frequency part is
      related to the inherent gain of the homogeneous non-phase-matched material and is
      a consistent spectral feature.

PMID- 11580590
TI  - Control of laser high-harmonic generation with counterpropagating light.
AB  - Relatively weak counterpropagating light is shown to disrupt the emission of
      laser high-harmonic generation. Harmonic orders ranging from the teens to the low
      thirties produced by a 30-femtosecond pulse in a narrow argon jet are "shut down"
      with a contrast as high as 2 orders of magnitude by a chirped 1-picosecond
      counterpropagating laser pulse (60 times less intense). Alternatively, under poor
      phase-matching conditions, the counterpropagating light boosts harmonic
      production by similar contrast through quasiphase matching where out-of-phase
      emission is suppressed.

PMID- 11580576
TI  - Measurement of d sigma/dM and forward-backward charge asymmetry for high-mass
      Drell-Yan e(+)e(-) pairs from pp macro collisions at square root of s = 1.8 TeV.
AB  - We report on a measurement of the mass dependence of the forward-backward charge
      asymmetry, A(FB), and production cross section d sigma/dM for e(+)e(-) pairs with
      mass M(ee)>40 GeV/c(2). The data sample consists of 108 pb(-1) of pp macro
      collisions at square root of s = 1.8 TeV taken by the Collider Detector at
      Fermilab during 1992-1995. The measured asymmetry and d sigma/dM are compared
      with the predictions of the standard model and a model with an extra Z' gauge
      boson.

PMID- 11580591
TI  - Ultrasonics without a source: thermal fluctuation correlations at MHz
      frequencies.
AB  - Noise generated in an ultrasonic receiver circuit consisting of transducer and
      amplifier is usually ignored, or treated as a nuisance. Here it is argued that
      acoustic thermal fluctuations, with displacement amplitudes of 3 fm, contain
      substantial ultrasonic information. It is shown that the noise autocorrelation
      function is the waveform that would be obtained in a direct pulse/echo
      measurement. That thesis is demonstrated in experiments in which direct
      measurements are compared to correlation functions. The thermal nature of the
      elastodynamic noise that generates these correlations is confirmed by an absolute
      measurement of their strength, essentially a measurement of the sample
      temperature.

PMID- 11580592
TI  - Structure formation and instability in a tube of sand.
AB  - A new instability in the combined flow of fine grains and gas is investigated by
      means of experiments, simulations, and analytic techniques. When a bubble of air
      rises through a granular packing in a tube, a sequence of smaller bubbles
      spontaneously forms in front of it. The existence of this instability is shown
      from the experiments, simulations, and theoretical considerations. Moreover, the
      simulations and experiments agree on the quantitative level. In particular, when
      the tube is tilted away from the vertical the experiments and the simulations
      show the same increase in the speed of the rising bubble.

PMID- 11580593
TI  - Laplacian growth and diffusion limited aggregation: different universality
      classes.
AB  - It had been conjectured that diffusion limited aggregates and Laplacian growth
      patterns (with small surface tension) are in the same universality class. Using
      iterated conformal maps we construct a one-parameter family of fractal growth
      patterns with a continuously varying fractal dimension. This family can be used
      to bound the dimension of Laplacian growth patterns from below. The bound value
      is higher than the dimension of diffusion limited aggregates, showing that the
      two problems belong to two different universality classes.

PMID- 11580594
TI  - Suppression of the sawtooth instability in a storage ring by free-electron laser:
      an example of nonlinear stabilization by noise.
AB  - The stabilization of nonlinear excitations by noise is a topic of fundamental
      importance in many physical problems. We discuss a genuine example within the
      context of storage ring-free electron laser physics, by presenting a model which
      allows the characterization of the system evolution and the determination of the
      conditions leading to the suppression of instabilities of sawtooth type. The
      conclusions of the model are confirmed by a comparison with experimental results
      on the Super Aco Storage Ring-Free Electron Laser.

PMID- 11580595
TI  - Saturation of bunch-wave interaction in an active medium.
AB  - We determine the set of equations which describe the dynamics of electrons in the
      presence of a wave propagating in an active medium. Simulation results indicate
      that, even when virtually all the energy is drained from the medium, electrons
      remain trapped by the accelerating wave. In spite of saturation, gradients of a
      few GV/m may become available.

PMID- 11580596
TI  - Increased nonlinear coupling between turbulence and low-frequency fluctuations at
      the L-H transition.
AB  - The nonlinear coupling between small scale high-frequency turbulence and larger
      scale lower-frequency fluctuations increases transiently in transitions to
      improved confinement in the DIII-D tokamak. This increase starts before the rapid
      turbulence suppression and E x B shear-flow development in the region that
      becomes the H-mode transport barrier/shear flow region. After the transition, the
      coupling returns to L-mode levels. These results are consistent with expectations
      for spontaneous transitions to improved confinement triggered by a turbulence
      driven sheared flow.

PMID- 11580597
TI  - Observation of the "self-healing" of an error field island in the large helical
      device.
AB  - It was observed that the vacuum magnetic island produced by an external error
      magnetic field in the large helical device shrank in the presence of plasma. This
      was evidenced by the disappearance of flat regions in the electron temperature
      profile obtained by Thomson scattering. This island behavior depended on the
      magnetic configuration in which the plasmas were produced.

PMID- 11580598
TI  - Measurements of viscosity in pure-electron plasmas.
AB  - Measurements of the viscosity in quiescent magnetized pure-electron plasmas are
      up to 10(8) times larger than predicted by classical collisional theory. This
      strong viscosity is due to long-range " E x B drift collisions" between electrons
      separated by up to a Debye length. Recent theories of long-range collisions show
      order-of-magnitude agreement with the measurements, but do not give the observed
      dependence on the plasma column length. A simple empirical scaling law fits the
      length and magnetic field dependence surprisingly well.

PMID- 11580599
TI  - Collisionless electron heating by capacitive rf sheaths.
AB  - High-frequency plasma discharges are often sustained by collisionless heating of
      electrons; the nature of these mechanisms is a central problem in the theory of
      such discharges. In capacitive discharges, collisionless heating occurs near
      boundaries, and is usually attributed to inelastic collisions of electrons with
      oscillating plasma sheaths, regarded as moving rigid barriers. We show that, when
      current conservation is required, such heating necessarily vanishes, and we
      conclude that this model of the heating process is not correct. We develop an
      alternative view that associates the heating with acoustic disturbances in the
      electron fluid. An analytic model, based on moments of the Vlasov equation, gives
      results in good agreement with particle-in-cell simulations. In terms of
      individual particle dynamics, this acoustic heating may be interpreted as a
      transit-time effect.

PMID- 11580600
TI  - Generation of an axial magnetic field from photon spin.
AB  - In circularly polarized light the spins of the photons are aligned. When a short
      intense pulse of circularly polarized laser light is absorbed by a plasma, a
      torque is delivered initially to the electron species, resulting primarily in an
      opposing torque from an induced azimuthal electric field. This electric field, in
      general, has a curl and leads to the generation of an axial magnetic field. It
      also is the main means for transferring angular momentum to the ions. The time
      dependent magnetic field has a magnitude proportional to the transverse gradient
      of the absorbed intensity but inversely proportional to the electron density, in
      contrast to earlier theories of the inverse Faraday effect.

PMID- 11580601
TI  - Heat-capacity studies of (3)He in (3)He-(4)He mixture films and the coverage
      dependence of the two-dimensional (3)He Landau Fermi-liquid parameters.
AB  - The heat capacity of (3)He in (3)He-(4)He mixture films on a nuclepore substrate
      is reported over the temperature range 90<T<124 mK, for (3)He coverages between
      0.05 and 1.4 bulk-density atomic layers, and a (4)He film thickness of 4.33 bulk
      density atomic layers. A step structure appears in the specific heat as a
      function of (3)He coverage. Combining NMR and specific heat data for (3)He atoms
      on the same substrate and for the same (4)He coverage allows the two-dimensional
      Landau Fermi-liquid parameters F(A)(0) and F(S)(1) to be extracted as a function
      of (3)He coverage. We conclude that in the submonalayer (3)He coverage regime p
      state pairing is favored.

PMID- 11580602
TI  - Matching conditions in atomistic-continuum modeling of materials.
AB  - A new class of matching conditions between the atomistic and continuum regions is
      presented for the multiscale modeling of crystals. They ensure the accurate
      passage of large scale information between the atomistic and continuum regions
      and at the same time minimize the reflection of phonons at the interface. These
      matching conditions can be made adaptive if we choose appropriate weight
      functions. Applications to dislocation dynamics and friction between two
      dimensional atomically flat crystal surfaces are described.

PMID- 11580603
TI  - Dynamic instability of strongly confined thin polymer films in spinodal
      dewetting.
AB  - We present a general criterion for determining the dynamic instability of a thin
      polymer film that is strongly confined to a substrate. When such a polymer film
      is heated above its glass transition temperature, it dewets from the substrate by
      a spinodal dewetting scenario, in which the onset of the instability is governed
      by dispersion force and residual thermal stress. It turns out that the thermal
      stress plays an important role when there is a special interaction between a
      polymer and a substrate.

PMID- 11580604
TI  - Graded nanostructures produced by sliding and exhibiting universal behavior.
AB  - Nanostructured copper was produced by deformation under large sliding loads. In
      the near surface layers, 10 nm scale microstructures form and coarsen with
      increasing depth from the surface. The graded structure enables characterization
      of the structural scale over several orders of magnitude. Analysis reveals that
      universal scaling of the microstructure exists from 10,000 to 10 nm. The limit of
      scale is pushed to an order of magnitude of the ultimate scale at which the
      crystallinity is lost. This universality opens the door for easy manufacture of
      ever finer scale components by deformation.

PMID- 11580605
TI  - Novel broken symmetry phase from N(2)O at high pressures and high temperatures.
AB  - Simple molecular solids become unstable at high pressures, typically transforming
      to dense framework and/or metallic structures. We report formation of an unusual
      ionic solid NO(+)NO(3)(-) (nitrosonium nitrate) from N(2)O at pressures above 20
      GPa and temperatures above 1000 K. Synchrotron x-ray diffraction indicates that
      the compound crystallizes with a structure related to the aragonite form of
      CaCO(3) and NaNO(3). Raman and infrared spectroscopic data indicate that the
      structure is noncentrosymmetric and exhibits a strong pressure dependent charge
      transfer and orientational order.

PMID- 11580606
TI  - Unusual scaling for pulsed laser deposition.
AB  - We show that a simple model for pulsed laser deposition exhibits an unusual type
      of scaling behavior for the island density in the submonolayer regime. This
      quantity is studied as a function of pulse intensity and deposition time. We find
      a data collapse for the ratios of the logarithms of these quantities, whereas
      conventional scaling as observed in molecular beam epitaxy involves ratios of
      powers.

PMID- 11580608
TI  - Morphology transition during low-pressure chemical vapor deposition.
AB  - Assuming a reemission model, we have studied, in detail, the effect of sticking
      coefficient on the morphology evolution in low-pressure chemical vapor deposition
      processes. We have shown that the surface morphology changes from a self-affine
      fractal to a columnarlike morphology with increasing sticking coefficient, which
      agrees qualitatively with experimental observations.

PMID- 11580607
TI  - Maximal height scaling of kinetically growing surfaces.
AB  - The scaling properties of the maximal height of a growing self-affine surface
      with a lateral extent L are considered. In the late-time regime its value
      measured relative to the evolving average height scales like the roughness: h*(L)
      approximately L alpha. For large values its distribution obeys logP(h*(L))
      approximately (-)A(h*(L)/L(alpha))(a). In the early-time regime where the
      roughness grows as t(beta), we find h*(L) approximately t(beta)[lnL
      (beta/alpha)lnt+C](1/b), where either b = a or b is the corresponding exponent of
      the velocity distribution. These properties are derived from scaling and extreme
      value arguments. They are corroborated by numerical simulations and supported by
      exact results for surfaces in 1D with the asymptotic behavior of a Brownian path.

PMID- 11580609
TI  - Enhanced terrace stability for preparation of step-free Si(001)-(2 x 1) surfaces.
AB  - We show that depositing Si while annealing patterned Si(001)-(2 x 1) substrates
      at sublimation temperatures enhances terrace stability, permitting larger step
      free areas to be produced in a given time than possible by annealing alone. We
      confirm this enhanced terrace stability using real-time low-energy electron
      microscopy observations, and quantitative microscopic modeling of step dynamics.
      Our measurements can be used to estimate the lateral variation in adatom
      concentration across large terraces, and to estimate an adatom diffusion length
      lambda approximately 10-30 microm at 1000 degrees C.

PMID- 11580610
TI  - Minute SiGe quantum dots on Si(001) by a kinetic 3D island mode.
AB  - We investigated the initial growth stages of Si(x)Ge(1-x)/Si(001) by real time
      stress measurements and in situ scanning tunneling microscopy at deposition
      temperatures, where intermixing effects are still minute (< or =900 K). Whereas
      Ge/Si(001) is a well known Stranski-Krastanow system, the growth of SiGe alloy
      films switches to a 3D island mode at Si content above 20%. The obtained islands
      are small (a few nanometers), are uniform in shape, and exhibit a narrow size
      distribution, making them promising candidates for future quantum dot devices.

PMID- 11580611
TI  - Consistency of superconducting correlations with one-dimensional electron
      interactions in carbon nanotubes.
AB  - We show that a model of interacting electrons in one dimension is able to explain
      the order of magnitude as well as the temperature dependence of the critical
      supercurrents recently measured in nanotube samples placed between
      superconducting contacts. We use bosonization methods to deal with the long-range
      Coulomb interaction, ending up with a picture in which the critical current does
      not follow the temperature dependence of the gap in the contacts. Our results
      also reveal the presence of a short-range attractive interaction in the
      nanotubes, which accounts for a significant enhancement of the critical
      supercurrents.

PMID- 11580612
TI  - Stochastic heterostructures and diodium in B/N-doped carbon nanotubes.
AB  - Carbon nanotubes are one dimensional and very narrow. These obvious facts imply
      that, under doping with boron and nitrogen, microscopic doping inhomogeneity is
      much more important than for bulk semiconductors. We consider the possibility of
      exploiting such fluctuations to create interesting devices. Using the self
      consistent tight-binding technique, we study heavily doped highly compensated
      nanotubes, revealing the spontaneous formation of structures resembling chains of
      random quantum dots, or nanoscale diodelike elements in series. We also consider
      truly isolated impurities, revealing simple scaling properties of bound state
      sizes and energies.

PMID- 11580613
TI  - Acoustically induced stark effect for excitons in intrinsic semiconductors.
AB  - A Stark effect for excitons parametrically driven by coherent acoustic phonons is
      proposed. Our scheme refers to a low-temperature intrinsic semiconductor or
      semiconductor nanostructure pumped by an acoustic wave (frequency band nu(ac)
      approximately equal to 1-40 GHz and intensity range I(ac) approximately equal to
      10(-2)-10(2) W/cm(2)) and probed by low-intensity light. Tunable optical band
      gaps, which strongly change the spectral shape of the exciton line, are induced
      in the polariton spectrum by acoustic pumping. We develop an exactly solvable
      model of the acoustic Stark effect and apply our results to GaAs driven by bulk
      or surface acoustic waves.

PMID- 11580614
TI  - New phase transition between partially and fully polarized quantum Hall states
      with charge and spin gaps at nu = 2/3.
AB  - The average electron spin polarization Rho of a two-dimensional electron gas
      confined in GaAs/GaAlAs multiple quantum wells was measured by NMR near the
      fractional quantum Hall state with filling factor nu = 2/3. Above this filling
      factor (2/3< or = nu < 0.85), a strong depolarization is observed corresponding
      to two spin flips per additional flux quantum. The most remarkable behavior of
      the polarization is observed at nu = 2/3, where a quantum phase transition from a
      partially polarized (Rho approximately 3/4) to a fully polarized (Rho = 1) state
      can be driven by increasing the ratio between the Zeeman and the Coulomb energy
      above a critical value eta(c) = Delta(Z)/Delta(C) = 0.0185.

PMID- 11580615
TI  - Superconducting single-charge transistor in a tunable dissipative environment.
AB  - We study a superconducting single-charge transistor, where the coherence of
      Cooper pair tunneling is destroyed by the coupling to a tunable dissipative
      environment. Sequential tunneling and cotunneling processes are analyzed to
      construct the shape of the conductance peaks and their dependence on the
      dissipation and temperature. Unexpected features are found due to a crossover
      between two distinct regimes, one "environment assisted" the other "environment
      dominated." Several of the predictions have been confirmed by recent experiments.
      The model and results apply also to the dynamics of Josephson junction quantum
      bits on a conducting ground plane, thus explaining the influence of dissipation
      on the coherence.

PMID- 11580616
TI  - Disorder driven melting of the vortex line lattice.
AB  - The 3D XY model with random in-plane couplings is simulated to model the phase
      diagram of a disordered type II superconductor as a function of temperature T and
      randomness strength p for fixed applied magnetic field. As p increases to a
      critical p(c), the first order vortex lattice melting line turns parallel to the
      T axis, continuing down to low temperatures, rather than ending at a critical
      point. Above p(c) preliminary results suggest the absence of a phase coherent
      vortex glass.

PMID- 11580617
TI  - Elastic moduli of vortex lattices within nonlocal London model.
AB  - Vortex lattice (VL) elastic response is analyzed within the nonlocal London model
      which holds for high-kappa clean superconductors. The squash modulus vanishes at
      the field H( square) where VL undergoes a square-to-rhombus transition. For H>H(
      square), where the square VL is stable, the rotation modulus turns zero at H =
      H(r), indicating VL instability to rotations. The shear modulus depends on the
      shear direction; the dependence is strong in the vicinity of H( square) where the
      square VL is soft with respect to the shear along [110]. The H dependences of the
      moduli are evaluated for LuNi(2)B(2)C.

PMID- 11580618
TI  - Direct measurement of the Josephson supercurrent in an ultrasmall Josephson
      junction.
AB  - We have measured the supercurrent flowing through a nonhysteretic, ultrasmall,
      voltage-biased Josephson junction. In contrast with experiments performed so far
      on hysteretic Josephson junctions, we find a supercurrent peak whose maximum I(s
      max) increases as the temperature T decreases. The asymptotic T = 0 value of I(s
      max) agrees with the junction Ambegaokar-Baratoff critical current, as predicted
      by theory.

PMID- 11580619
TI  - Quantum critical points with the Coulomb interaction and the dynamical exponent:
      when and why z = 1.
AB  - A general scenario that leads to Coulomb quantum criticality with the dynamical
      critical exponent z = 1 is proposed. I point out that the long-range Coulomb
      interaction and quenched disorder have competing effects on z, and that balance
      between the two may lead to charged quantum critical points at which z = 1
      exactly. This is illustrated with the calculation for the Josephson junction
      array Hamiltonian in dimensions D = 3 - epsilon. Precisely in D = 3, however, the
      above simple result breaks down, and z > 1. Relation to other studies is
      discussed.

PMID- 11580620
TI  - Evidence for two superconducting energy gaps in MgB(2) by point-contact
      spectroscopy.
AB  - Experimental support is found for the multiband model of the superconductivity in
      the recently discovered system MgB(2) with the transition temperature T(c) = 39
      K. By means of Andreev reflection, evidence is obtained for two distinct
      superconducting energy gaps. The sizes of the two gaps ( Delta(S) = 2.8 meV and
      Delta(L) = 7 meV) are, respectively, smaller and larger than the expected weak
      coupling value. Because of the temperature smearing of the spectra the two gaps
      are hardly distinguishable at elevated temperatures, but when a magnetic field is
      applied the presence of two gaps can be demonstrated close to the bulk T(c) in
      the raw data.

PMID- 11580621
TI  - Effect of magnetic doping on the electronic states of Ni.
AB  - Angle-resolved photoemission is used to determine the change in the electronic
      states of Ni induced by doping with Fe and Cr. Well-defined spin and k states are
      selected using high energy and k resolution combined with single crystal alloys.
      Iron suppresses the mean free path of minority spins only, while chromium
      suppresses both spins and decreases the magnetic splitting. The strong variation
      of these effects from one impurity to the other supports the concept of magnetic
      doping.

PMID- 11580622
TI  - Second harmonic generation in the centrosymmetric antiferromagnet NiO.
AB  - In spite of the fact that inversion is a symmetry operation of both the
      crystalline and the magnetic lattice of NiO, second harmonic generation (SHG) has
      been observed below the Neel temperature. A spectroscopic study shows that the
      signal is due to combined magnetic-dipole and electric-dipole transitions between
      the (3d)(8) levels of the Ni(2+) ion in the crystal field. The SHG is resonant in
      both the incoming and the outgoing light waves and thus greatly enhanced. A
      quadratic coupling of the nonlinear polarization to the order parameter was
      found. This allows the investigation of individual domains.

PMID- 11580623
TI  - Absence of spontaneous magnetic order at nonzero temperature in one- and two
      dimensional Heisenberg and XY systems with long-range interactions.
AB  - The Mermin-Wagner theorem is strengthened so as to rule out magnetic long-range
      order at T > 0 in one- or two-dimensional Heisenberg and XY systems with long
      range interactions decreasing as R(-alpha) with a sufficiently large exponent
      alpha. For oscillatory interactions, ferromagnetic long-range order at T > 0 is
      ruled out if alpha > or = 1(D = 1) or alpha > 5/2(D = 2). For systems with
      monotonically decreasing interactions, ferro- or antiferromagnetic long-range
      order at T > 0 is ruled out if alpha > or = 2D.

PMID- 11580624
TI  - Two-phase character of metallic ferromagnetism in manganites.
AB  - (55)Mn NMR spectra of several ferromagnetic manganites, including
      La(0.7)Ca(0.3)MnO(3) and La(0.7)Sr(0.3) MnO(3), were measured as a function of
      temperature. A thorough analysis of the spin-spin relaxation and the NMR line
      shape revealed that in these compounds two different ferromagnetic phases coexist
      below T(C) in a certain temperature interval which depends on the composition.
      The phase with lower hyperfine field has faster nuclear relaxation, its
      characteristic dimension is a few nm, and its volume decreases with decreasing
      temperature. The NMR lines of both phases are motionally narrowed, i.e., the
      electron holes are mobile.

PMID- 11580625
TI  - Direct investigation of superparamagnetism in Co nanoparticle films.
AB  - A direct probe of superparamagnetism was used to determine the complete
      anisotropy energy distribution of Co nanoparticle films. The films were composed
      of self-assembled lattices of uniform Co nanoparticles of 3 or 5 nm in diameter,
      and a variable temperature scanning-SQUID microscope was used to measure
      temperature-induced spontaneous magnetic noise in the samples. Accurate
      measurements of anisotropy energy distributions of small volume samples will be
      critical to magnetic optimization of nanoparticle devices and media.

PMID- 11580626
TI  - Entanglement capabilities of nonlocal Hamiltonians.
AB  - We quantify the capability of creating entanglement for a general physical
      interaction acting on two qubits. We give a procedure for optimizing the
      generation of entanglement. We also show that a Hamiltonian can create more
      entanglement if one uses auxiliary systems.

PMID- 11580627
TI  - Preparation of entangled states by adiabatic passage.
AB  - We propose a novel technique for the creation of entangled pairs of two-state
      systems based upon adiabatic passage induced by a suitably crafted time-dependent
      external field.

PMID- 11580628
TI  - Detecting the inseparability and distillability of continuous variable states in
      Fock space.
AB  - The partial transposition (PT) operation is an efficient tool in detecting the
      inseparability of a mixed state. We give an explicit formula for the PT operation
      for the continuous variable states in Fock space. We then give the necessary and
      sufficient condition for the positivity of Gaussian operators. Based on this, a
      number of criteria on the inseparability and distillability for the multimode
      Gaussian states are naturally drawn. We finally give an explicit formula for the
      state in a subspace of a global Gaussian state. This formula, together with the
      known results for Gaussian states, gives the criteria for the inseparability and
      distillability in a subspace of the global Gaussian state.

PMID- 11580629
TI  - Self-propagating patterns in active filament bundles.
AB  - Bundles of polar filaments which interact via active elements can exhibit complex
      dynamic behaviors. By using a simple and general description for the bundle
      dynamics, we find regimes for which density profiles propagate as solitary waves
      with a characteristic velocity along the bundle. These behaviors emerge from an
      interplay of local contractions in the bundle and relative sliding of oppositely
      oriented filaments. By introducing filament binding to and detachment from a
      substrate, the system is able to generate net motion as a self-organization
      phenomenon.

PMID- 11580630
TI  - Comment on "Thermal effects on the Casimir force in the 0.1-5 microm range".

PMID- 11580632
TI  - Domain wall solitons in binary mixtures of Bose-Einstein condensates.
AB  - The structure and dynamics of the domain walls separating segregated condensates
      in trapped mixtures of repulsive Bose-Einstein condensates are studied. Our work
      reveals that, under fairly general conditions, these domain walls behave as
      independent dynamical entities, which allows us to identify them as constituting
      a novel class of multicomponent solitons in Bose-Einstein condensates.

PMID- 11580633
TI  - Bloch oscillations and mean-field effects of Bose-Einstein condensates in 1D
      optical lattices.
AB  - We have loaded Bose-Einstein condensates into one-dimensional, off-resonant
      optical lattices and accelerated them by chirping the frequency difference
      between the two lattice beams. For small values of the lattice well depth, Bloch
      oscillations were observed. Reducing the potential depth further, Landau-Zener
      tunneling out of the lowest lattice band, leading to a breakdown of the
      oscillations, was also studied and used as a probe for the effective potential
      resulting from mean-field interactions as predicted by Choi and Niu [Phys. Rev.
      Lett. 82, 2022 (1999)]. The effective potential was measured for various
      condensate densities and trap geometries, yielding good qualitative agreement
      with theoretical calculations.

PMID- 11580634
TI  - Structural instability of vortices in Bose-Einstein condensates.
AB  - In this paper we study a gaseous Bose-Einstein condensate and show the following:
      (i) A minimum value of the interaction is needed for the existence of stable
      persistent currents. (ii) Vorticity is not a fundamental invariant of the system,
      as there exists a conservative mechanism which can destroy a vortex and change
      its sign. (iii) This mechanism is suppressed by strong interactions.

PMID- 11580636
TI  - Ferromagnetism in a lattice of Bose-Einstein condensates.
AB  - We show that an ensemble of spinor Bose-Einstein condensates confined in a one
      dimensional optical lattice can undergo a ferromagnetic phase transition and
      spontaneous magnetization arises due to the magnetic dipole-dipole interaction.
      This phenomenon is analogous to ferromagnetism in solid state physics, but occurs
      with bosons instead of fermions.

PMID- 11580635
TI  - Periodic orbit description of nonadiabatic quantum dynamics.
AB  - Classical periodic orbits associated with the nonadiabatic dynamics of a spin
      boson-type problem are introduced. To facilitate a classical description of spin
      states, the formulation employs an exact mapping of the discrete quantum
      variables onto continuous degrees of freedom. Adopting a one-dimensional spin
      boson model, the shortest periodic orbits of the problem are identified and used
      to analyze the nonadiabatic quantum dynamics. The possibility of directly
      observing these vibronic periodic orbits in femtosecond time-resolved experiments
      is discussed.

PMID- 11580637
TI  - Characterization of the transverse coherence of hard synchrotron radiation by
      intensity interferometry.
AB  - The transverse coherence of x rays was measured with an intensity interferometer
      using a 120-microeV-bandwidth monochromator operating at 14.41 keV. By analyzing
      the transverse coherence profiles, a vertical source profile of a 25-m long
      undulator of SPring-8, as well as the coherence degradation by a phase object in
      the beam path, were quantitatively characterized.

PMID- 11580638
TI  - Q-ball candidates for self-interacting dark matter.
AB  - We show that nontopological solitons, known as Q-balls, are promising candidates
      for self-interacting dark matter. They can satisfy the cross-section requirements
      for a broad range of masses. Unlike previously considered examples, Q-balls can
      stick together after collision, reducing the effective self-interaction rate to a
      negligible value after a few collisions per particle. This feature modifies
      predictions for halo formation. We also discuss the possibility that Q-balls have
      large interaction cross sections with ordinary matter.

PMID- 11580639
TI  - Testing the cosmic coincidence problem and the nature of dark energy.
AB  - Dark energy models which alter the relative scaling behavior of dark energy and
      matter could provide a natural solution to the cosmic coincidence problem-why the
      densities of dark energy and dark matter are comparable today. A generalized
      class of dark energy models is introduced which allows noncanonical scaling of
      the ratio of dark matter and dark energy with the Robertson-Walker scale factor
      a(t). We show that determining whether there is a coincidence problem, and the
      extent of cosmic coincidence, can be addressed by several forthcoming
      experiments.

PMID- 11580640
TI  - Noncommutative field theory and Lorentz violation.
AB  - The role of Lorentz symmetry in noncommutative field theory is considered. Any
      realistic noncommutative theory is found to be physically equivalent to a subset
      of a general Lorentz-violating standard-model extension involving ordinary
      fields. Some theoretical consequences are discussed. Existing experiments bound
      the scale of the noncommutativity parameter to (10 TeV)(-2).

PMID- 11580643
TI  - Parton energy loss with detailed balance.
AB  - Stimulated gluon emission and thermal absorption, in addition to induced
      radiation, are considered for an energetic parton propagating inside a quark
      gluon plasma. In the presence of thermal gluons, stimulated emission reduces,
      while absorption increases, the parton's energy. The net effect is a reduction of
      the parton energy loss. Though decreasing asymptotically as T/E with the parton
      energy, the relative reduction is found to be important for intermediate
      energies. The modified energy dependence of the energy loss will affect the shape
      of suppression of moderately high p(T) hadrons due to jet quenching in high
      energy heavy-ion collisions.

PMID- 11580641
TI  - Search for the decay upsilon(1S) --> gammaeta(').
AB  - We report on a search for the radiative decay Upsilon(1S)-->gammaeta(') in 61.3
      pb(-1) of data taken with the CLEO II detector at the Cornell Electron Storage
      Ring. Three decay chains were investigated, all involving eta(')-->pi(+)pi(-)eta,
      followed by eta-->gammagamma, eta-->pi(0)pi(0)pi(0), or eta-->pi(+)pi(-)pi(0). We
      find no candidate events in any of the three cases and set a combined upper limit
      of 1.6x10(-5) at 90% C.L., significantly smaller than the previous limit. We
      compare our result to other radiative Upsilon decays, to radiative J/psi decays,
      and to theoretical predictions.

PMID- 11580644
TI  - Generalized parton distributions in the deuteron.
AB  - We introduce generalized quark and gluon distributions in the deuteron, which can
      be measured in exclusive processes like deeply virtual Compton scattering and
      meson electroproduction. We discuss the basic properties of these distributions
      and point out how they probe the interplay of nucleon and parton degrees of
      freedom in the deuteron wave function.

PMID- 11580645
TI  - Breakdown of the isobaric multiplet mass equation at A = 33, T = 3/2.
AB  - Mass measurements on (33,34,42,43)Ar were performed using the Penning trap mass
      spectrometer ISOLTRAP and a newly constructed linear Paul trap. This arrangement
      allowed us, for the first time, to extend Penning trap mass measurements to
      nuclides with half-lives below one second ( 33Ar: T(1/2) = 174 ms). A mass
      accuracy of about 10(-7) (deltam approximately 4 keV) was achieved for all
      investigated nuclides. The isobaric multiplet mass equation was checked for the A
      = 33, T = 3/2 quartet and found to be inconsistent with the generally accepted
      quadratic form.

PMID- 11580646
TI  - Identification of the I(pi) = 10(+) Yrast rotational state in 24Mg.
AB  - Spins and parities of high spin states above the particle-binding threshold in
      24Mg were determined with a basis expansion technique using triple and quadruple
      angular correlations between alpha particles and gamma rays. The first
      unambiguous identification of a 10(+) state is reported. Located at 19.2(1) MeV,
      this state decays predominantly by alpha emission, although a candidate gamma
      decay branch with a 5.927 MeV transition connecting this 10(+) level to the
      rotational 8(+) state at 13.2 MeV was identified as well. The corresponding gamma
      alpha branching ratio is 7(3)x10(-4).

PMID- 11580647
TI  - Control of near-threshold detachment cross sections via laser polarization.
AB  - The behavior of near-threshold cross sections for dissociation of a target into a
      pair of particles, as described by Wigner's threshold law, can depend sensitively
      on the angular momentum of the particles. In this Letter, we investigate the near
      threshold nonresonant two-photon detachment process in the negative ion of gold.
      The expected s-wave threshold behavior is observed with linearly polarized light.
      Closure of the s-wave channel is realized by using circular polarization,
      allowing the first observation of a d-wave threshold. Practical applications are
      discussed, including extensions which could prove valuable for investigations of
      negative ions with near-threshold structure.

PMID- 11580648
TI  - Rydberg molecules in external fields: a semiclassical analysis.
AB  - We analyze the spectra of simple Rydberg molecules in static fields within the
      framework of closed/periodic-orbit theories. We conclude that in addition to the
      usual classical orbits one must consider classically forbidden diffractive paths.
      Further, the molecule brings in a new type of "inelastic" diffractive trajectory
      in addition to the usual "elastic" diffractive orbits encountered in systems with
      point scatterers. The relative importance of inelastic versus elastic diffraction
      is quantified by merging the usual closed orbit theory framework with molecular
      quantum defect theory.

PMID- 11580649
TI  - Asymmetry of the natural line profile for the hydrogen atom.
AB  - The asymmetry of the natural line profile for transitions in hydrogenlike atoms
      is evaluated within a QED framework. For the Lyman- alpha 1s-2p absorption
      transition in neutral hydrogen this asymmetry results in an additional energy
      shift of 2.929 856 Hz. For the 2s(1/2)-2p(3/2) transition it amounts to -1.512
      674 Hz. As a new feature this correction turns out to be process dependent. The
      quoted numbers refer to the Compton-scattering process.

PMID- 11580650
TI  - Wall relaxation of 3He in spin-exchange cells.
AB  - The 3He longitudinal spin-relaxation rate T1-1 is crucial for production of
      highly polarized 3He by spin-exchange optical pumping. We show that T1-1 is
      increased by a factor of 2-20 solely by exposure of spin-exchange cells to a few
      kG magnetic field. The original T1-1 can be restored by degaussing the cell. The
      effect is attributed to magnetic surface sites and has been observed in both
      Pyrex and aluminosilicate-glass cells. Our results both advance the understanding
      of wall relaxation and demonstrate the use of 3He as an extremely sensitive probe
      of surface magnetism.

PMID- 11580651
TI  - Rotating propeller solitons.
AB  - We demonstrate experimentally and theoretically (both analytically and
      numerically) a new type of spatial soliton: a rotating "propeller" soliton. This
      is a composite soliton made of a rotating dipole component jointly trapped with a
      bell-shaped component. We observe as much as 239 degrees of rotation over 13 mm
      of propagation (6.5 diffraction lengths).

PMID- 11580652
TI  - Thermal plumes and convection in highly compressible fluids.
AB  - We present simple hydrodynamic equations of supercritical fluids close to the gas
      liquid critical point. We numerically solve them to examine plume generation and
      convection under gravity. These results are in good agreement with the experiment
      [A. B. Kogan and H. Meyer, Phys. Rev. E 63, 056310 (2001)]. This Letter is a
      first study of transient behavior of convection, which is unique in compressible
      fluids due to the piston effect.

PMID- 11580653
TI  - NMR imaging of falling water drops.
AB  - The falling water drop is a simple model for studying phenomena related to
      chemical extraction, where two immiscible phases are dynamically blended to
      promote the transport of solute molecules from one phase to the other. Convective
      motion inside the drop significantly influences the extraction efficiency.
      Whereas optical and tracer methods are model bound or invasive, NMR imaging is
      noninvasive, direct, and applicable to nontransparent media. The first NMR
      measurements of a water drop falling through air are reported. It is shown that,
      in drops from pure water, large-scale convection rolls are observed in contrast
      to drops with the surface tension lowered by surfactants.

PMID- 11580654
TI  - Observation of compressional Alfven modes during neutral-beam heating on the
      national spherical torus experiment.
AB  - Neutral-beam-driven compressional Alfven eigenmodes at frequencies below the ion
      cyclotron frequency have been observed and identified for the first time in the
      National Spherical Torus Experiment. The modes are observed as a broad spectrum
      of nearly equally spaced peaks in the frequency range from approximately
      0.2omega(ci) to approximately 1.2omega(ci). The frequency has a scaling with
      toroidal field and plasma density consistent with Alfven waves. The modes have
      been observed with high bandwidth magnetic pickup coils and with a reflectometer.

PMID- 11580655
TI  - Two-dimensional space-charge-limited emission: beam-edge characteristics and
      applications.
AB  - There is, at present, no analytic solution that extends Child-Langmuir space
      charge-limited emission beyond 1D. Herein, we investigate the characteristics of
      planar diode electron emission in 2D space with the emphasis on the transition
      region between the beam and vacuum. Current density above that predicted by Child
      Langmuir is observed near the beam edges in a 2D finite element, electrostatic
      ray-tracing code. The properties of these increased current density "wings" are
      examined and then discussed in terms of their applications to cathodes which have
      large reservoirs of free electrons.

PMID- 11580656
TI  - Effect of shock heating on the stability of laser-driven targets.
AB  - The shock heating of a laser-driven, direct-drive target can determine its
      stability by affecting Rayleigh-Taylor growth rates through target decompression
      and ablative stabilization. Measurements indicate that pulses that rise rapidly
      to 10(14) W/cm(2) produce shock-induced temperatures of approximately 25 eV,
      whereas more slowly rising pulses show less heating. Analysis of the observed
      target behavior produced by these two pulses demonstrates that shock heating
      improves hydrodynamic stability because ablative stabilization increases when the
      targets are preheated by shocks.

PMID- 11580657
TI  - Measurement of instability growth in a magnetized Z pinch in the finite-Larmor
      radius regime.
AB  - The development of the m = 0 instability in a Z pinch was followed and the
      measured growth rates compared with 2D MHD simulations. Where MHD is valid, the
      measured growth rates agree well with simulation. Where the ions are magnetized,
      i.e., where the ion-cyclotron frequency is smaller than the ion-collision
      frequency and the ratio of the ion Larmor radius to pinch radius is of the order
      of 0.1, the growth rate was smaller than expected by a factor of 2.5. This is as
      predicted by finite-Larmor-radius theory. The product of the wave number and the
      pinch radius was ka approximately 2pi and was the same for all conditions.
      Perturbations as large as 30% of the pinch radius were observed; no nonlinear
      saturation was evident.

PMID- 11580658
TI  - Quantized vortices in mixed 3He-4He drops.
AB  - Using density functional theory, we investigate the structure of mixed (3)He(N3)
      (4)He(N4) droplets with an embedded impurity (Xe atom or HCN molecule) which pins
      a quantized vortex line. We find that the dopant+vortex+(4)He(N4) complex, which
      in a previous work [F. Dalfovo et al., Phys. Rev. Lett. 85, 1028 (2000)] was
      found to be energetically stable below a critical size N(cr), is robust against
      the addition of 3He. While 3He atoms are distributed along the vortex line and on
      the surface of the 4He drop, the impurity is mostly coated by 4He atoms. Results
      for N4 = 500 and a number of 3He atoms ranging from 0 to 100 are presented, and
      the binding energy of the dopant to the vortex line is determined.

PMID- 11580642
TI  - Double diffraction dissociation at the Fermilab Tevatron collider.
AB  - We present results from a measurement of double diffraction dissociation in pp
      collisions at the Fermilab Tevatron collider. The production cross section for
      events with a central pseudorapidity gap of width Deltaeta(0)>3 (overlapping eta
      = 0) is found to be 4.43+/-0.02(stat)+/-1.18(syst) mb [ 3.42+/-0.01(stat)+/
      1.09(syst) mb] at square root of (s) = 1800[630] GeV. Our results are compared
      with previous measurements and with predictions based on Regge theory and
      factorization.

PMID- 11580659
TI  - Anomaly in the stability limit of liquid 3He.
AB  - We propose that the liquid-gas spinodal line of 3He reaches a minimum at 0.4 K.
      This feature is supported by our cavitation measurements. We also show that it is
      consistent with extrapolations of sound-velocity measurements. Speedy [J. Phys.
      Chem. 86, 3002 (1982)] previously proposed this peculiar behavior for the
      spinodal of water and related it to a change in sign of the expansion coefficient
      alpha, i.e., a line of density maxima. 3He exhibits such a line at positive
      pressure. We consider its extrapolation to negative pressure. Our discussion
      raises fundamental questions about the sign of alpha in a Fermi liquid along its
      spinodal.

PMID- 11580661
TI  - In situ X-ray absorption fine structure detection of reversible photoinduced
      anisotropy in amorphous selenium.
AB  - Photoinduced anisotropy in amorphous selenium ( a-Se) has been studied by in situ
      x-ray absorption fine structure spectroscopy. It is found that upon irradiation
      with linearly polarized light the chainlike fragments in a-Se are oriented with
      their c-axis perpendicular to the polarization plane of the inducing light. This
      chain orientation is reversible, correlates with optical anisotropy, and acts as
      a prelude to photoinduced anisotropic crystallization. This optically controlled
      reorientation of molecular fragments in a solid can be a basis for future novel
      devices.

PMID- 11580660
TI  - Lifetimes of hydrogen and deuterium related vibrational modes in silicon.
AB  - Lifetimes of hydrogen and deuterium related stretch modes in Si are measured by
      high-resolution infrared absorption spectroscopy and transient bleaching
      spectroscopy. The lifetimes are found to be extremely dependent on the defect
      structure, ranging from 2 to 295 ps. Against conventional wisdom, we find that
      lifetimes of Si-D modes typically are longer than for the corresponding Si-H
      modes. The potential implications of the results on the physics of electronic
      device degradation are discussed.

PMID- 11580662
TI  - Nanoscale manipulation of pyrochlore: new nanocomposite ionic conductors.
AB  - The ionic conductivity of isometric pyrochlore, ideally A2B2O (7), is extremely
      sensitive to disordering of A- and B-site cations and oxygen anion vacancies. We
      report the first use of ion beam irradiation-induced disordering in Gd 2Ti 2O (7)
      to produce a strain-free, buried, disordered defect-fluorite layer approximately
      12 nm thick within an ordered pyrochlore matrix. This approach provides a new
      means of creating nanoscale, mixed ionic-electronic conductors in pyrochlore
      ceramics, such as those required for solid-state electrochemical cells.

PMID- 11580663
TI  - Particle-hole symmetry and the effect of disorder on the Mott-Hubbard insulator.
AB  - The understanding of the interplay of electron correlations and randomness in
      solids is enhanced by demonstrating that particle-hole ( p-h) symmetry plays a
      crucial role in determining the effects of disorder on the transport and
      thermodynamic properties of the half-filled Hubbard Hamiltonian. We show that the
      low-temperature conductivity decreases with increasing disorder when p-h symmetry
      is preserved, and shows the opposite behavior, i.e., conductivity increases with
      increasing disorder, when p-h symmetry is broken. The Mott insulating gap is
      insensitive to weak disorder when there is p-h symmetry, whereas in its absence
      the gap diminishes with increasing disorder.

PMID- 11580664
TI  - Magnetic quantum dot: a magnetic transmission barrier and resonator.
AB  - We study the ballistic edge-channel transport in quantum wires with a magnetic
      quantum dot, which is formed by two different magnetic fields B(*) and B0 inside
      and outside the dot, respectively. We find that the electron states located near
      the dot and the scattering of edge channels by the dot strongly depend on whether
      B(*) is parallel or antiparallel to B0. For parallel fields, two-terminal
      conductance as a function of channel energy is quantized except for resonances,
      while, for antiparallel fields, it is not quantized and all channels can be
      completely reflected in some energy ranges. All these features are attributed to
      the characteristic magnetic confinements caused by nonuniform fields.

PMID- 11580665
TI  - Anomalous acoustoelectric effect in La0.67Ca0.33MnO3 films.
AB  - We have studied the acoustoelectric (AE) effect produced by surface acoustic
      waves (SAW) in a monolithic layered structure, composed of a piezodielectric
      LiNbO3 substrate and a La0.67Ca0.33MnO3 film. The experiments unexpectedly
      revealed in the longitudinal AE effect an anomalous contribution, invariant upon
      reversal of SAW propagation, which coexists with the ordinary (odd in wave
      vector) effect. The anomalous effect dominates near the metal-insulator
      transition, while the ordinary effect prevails at high and low temperatures. We
      show that the anomalous effect is caused by strong modulation of the film
      conductivity produced by the SAW elastic deformations.

PMID- 11580666
TI  - Nature of charge transport in quantum-cascade lasers.
AB  - The first global quantum simulation of semiconductor-based quantum-cascade lasers
      is presented. Our three-dimensional approach allows us to study in a purely
      microscopic way the current-voltage characteristics of state-of-the-art unipolar
      nanostructures, and therefore to answer the long-standing controversial question:
      Is charge transport in quantum-cascade lasers mainly coherent or incoherent? Our
      analysis shows that (i) quantum corrections to the semiclassical scenario are
      minor and (ii) inclusion of carrier-phonon and carrier-carrier scattering gives
      excellent agreement with experimental results.

PMID- 11580667
TI  - Absence of compressible edge channel rings in quantum antidots.
AB  - We report resonant tunneling experiments in a quantum antidot sample in the
      integer quantum Hall regime. In particular, we have measured the temperature T
      dependence of the peak value of a conductance peak on the i = 2 plateau, where
      there are two peaks per magnetic flux quantum straight phi(0). We observe a T-1
      dependence as expected when tunneling through only one electron state is
      possible. This result is incompatible with tunneling through a compressible ring
      of several degenerate states. We also observe, for the first time, three
      conductance peaks per straight phi(0) on the i = 3 plateau.

PMID- 11580668
TI  - Control of spin in quantum dots with non-Fermi-liquid correlations.
AB  - Spin effects in the transport properties of a quantum dot with spin-charge
      separation are investigated. It is found that the nonlinear transport spectra are
      dominated by spin dynamics. Strong spin polarization effects are observed in a
      magnetic field. They can be controlled by varying gate and bias voltages.
      Complete polarization is stable against interactions. When polarization is not
      complete it is power law enhanced by non-Fermi-liquid effects.

PMID- 11580669
TI  - Magnetic ordering in hexagonally bonded sheets with first-row elements.
AB  - We report first-principles total-energy electronic-structure calculations in the
      density-functional theory performed for hexagonally bonded honeycomb sheets
      consisting of B, N, and C atoms. We find that the ground state of BNC sheets with
      particular stoichiometry is ferromagnetic. Detailed analyses of energy bands and
      spin densities unequivocally reveal the nature of the ferromagnetic ordering,
      leading to an argument that the BNC sheet is a manifestation of the flat-band
      ferromagnetism.

PMID- 11580670
TI  - Indication of superconductivity at 35 K in graphite-sulfur composites.
AB  - We report magnetization measurements performed on graphite-sulfur composites
      which demonstrate a clear superconducting behavior below the critical temperature
      T(c0) = 35 K. The Meissner-Ochsenfeld effect, screening supercurrents, and
      magnetization hysteresis loops characteristic of type-II superconductors were
      measured. The results indicate that the superconductivity occurs in a small
      sample fraction, possibly related to the sample surface.

PMID- 11580671
TI  - Quasiparticle states at a d-wave vortex core in high- T(c) superconductors:
      induction of local spin density wave order.
AB  - The local density of states (LDOS) at the vortex lattice cores in a high- T(c)
      superconductor is studied by using a self-consistent mean-field theory including
      interactions for both antiferromagnetism (AF) and d-wave superconductivity (DSC).
      In a zero-field optimally doped sample the AF order is completely suppressed
      while DSC prevails. In the mixed state, we show that the local AF-like spin
      density wave order appears near the vortex core and acts as an effective local
      magnetic field on electrons via Zeeman coupling. As a result, the LDOS at the
      core exhibits a double-peak structure near the Fermi level that is in good
      agreement with recent scanning tunneling microscopy observations.

PMID- 11580672
TI  - Anomalous electronic structure and pseudogap effects in Nd1.85Ce0.15CuO4.
AB  - We report a high-resolution angle-resolved photoemission spectroscopic study of
      the electron-doped ( n-type) cuprate superconductor Nd1.85Ce0.15CuO4. We observe
      regions along the Fermi surface where the near- E(F) intensity is suppressed and
      the spectral features are broad in a manner reminiscent of the high-energy
      "pseudogap" in the underdoped p-type (hole doped) cuprates. However, instead of
      occurring near the (pi,0) region, as in the p-type materials, this pseudogap
      falls near the intersection of the underlying Fermi surface with the
      antiferromagnetic Brillouin zone boundary.

PMID- 11580673
TI  - Structural transition and pair formation in Fe3O2BO3.
AB  - We observe for the first time a structural phase transition in the oxyborate
      Fe3O2BO3 which occurs along three leg ladders present in this material. X-ray
      diffraction shows that this transition at 283 K is associated with a new phase
      where atomic displacements occur in alternate directions perpendicular to the
      axis and within the plane of the ladders. Magnetic data show that these
      displacements lead to the formation of singlet pairs which dissociate close to
      the structural transition. Anomalies in the transport properties also occur close
      to 283 K showing that the structural transition is related to a charge ordering
      phenomenon in a low dimensional structure.

PMID- 11580674
TI  - Direct observation of terahertz surface modes in nanometer-sized liquid water
      pools.
AB  - The far-infrared absorption spectrum of nanometer-sized water pools at the core
      of AOT micelles exhibits a pronounced resonance which is absent in bulk water.
      The amplitude and spectral position of this resonance are sensitive to the size
      of the confined water core. This resonance results from size-dependent
      modifications in the vibrational density of states, and thus has far-reaching
      implications for chemical processes which involve water sequestered within small
      cavities. These data represent the first study of the terahertz dielectric
      properties of confined liquids.

PMID- 11580675
TI  - Phase sensitive x-ray diffraction imaging of defects in biological macromolecular
      crystals.
AB  - Conventional x-ray diffraction topography is currently used to map defects in the
      bulk of protein crystals, but the lack of sufficient contrast is frequently a
      limiting factor. We experimentally demonstrate that this barrier can be
      circumvented using a method that combines phase sensitive and diffraction imaging
      principles. Details of defects revealed in tetragonal lysozyme and cubic ferritin
      crystals are presented and discussed. The approach enabling the detection of the
      phase changes of diffracted x rays should prove to be useful in the study of
      defect structures in a broad range of biological macromolecular crystals.

PMID- 11580676
TI  - Scaling the microrheology of living cells.
AB  - We report a scaling law that governs both the elastic and frictional properties
      of a wide variety of living cell types, over a wide range of time scales and
      under a variety of biological interventions. This scaling identifies these cells
      as soft glassy materials existing close to a glass transition, and implies that
      cytoskeletal proteins may regulate cell mechanical properties mainly by
      modulating the effective noise temperature of the matrix. The practical
      implications are that the effective noise temperature is an easily quantified
      measure of the ability of the cytoskeleton to deform, flow, and reorganize.

PMID- 11580677
TI  - Universal negative poisson ratio of self-avoiding fixed-connectivity membranes.
AB  - We determine the Poisson ratio of self-avoiding fixed-connectivity membranes,
      modeled as impenetrable plaquettes, to be sigma = -0.37(6), in statistical
      agreement with the Poisson ratio of phantom fixed-connectivity membranes sigma = 
      0.32(4). Together with the equality of critical exponents, this result implies a
      unique universality class for fixed-connectivity membranes. Our findings thus
      establish that physical fixed-connectivity membranes provide a wide class of
      auxetic (negative Poisson ratio) materials with significant potential
      applications in materials science.

PMID- 11580678
TI  - Nonlinear network dynamics on earthquake fault systems.
AB  - Earthquake faults occur in interacting networks having emergent space-time modes
      of behavior not displayed by isolated faults. Using simulations of the major
      faults in southern California, we find that the physics depends on the elastic
      interactions among the faults defined by network topology, as well as on the
      nonlinear physics of stress dissipation arising from friction on the faults. Our
      results have broad applications to other leaky threshold systems such as
      integrate-and-fire neural networks.

PMID- 11580679
TI  - Comment on "determination of interlayer diffusion parameters for Ag/Ag(111)".

PMID- 11580681
TI  - Comment on "determination of interlayer diffusion parameters for Ag/Ag(111)".

PMID- 11580685
TI  - Comment on "magnetic correlations in nanostructured ferromagnets".

PMID- 11580683
TI  - Comment on "determination of interlayer diffusion parameters for Ag/Ag(111)".

PMID- 11580687
TI  - Multiparticle quantum superposition and stimulated entanglement by parity
      selective amplification of entangled states.
AB  - We report the creation of an entangled multiphoton quantum superposition by
      quantum injection of entangled 2-photon states into a parity selective parametric
      amplifier. The information preserving property of the state transformation
      suggests for these macrostates the name of large qubits. They are ideal objects
      for investigating the emergence of the classical world in complex quantum systems
      and have relevant new applications in quantum information.

PMID- 11580688
TI  - Free energy functional for nonequilibrium systems: an exactly solvable case.
AB  - We consider the steady state of an open system in which there is a flux of matter
      between two reservoirs at different chemical potentials. For a large system of
      size N, the probability of any macroscopic density profile rho(x) is exp[
      NF([rho])]; F thus generalizes to nonequilibrium systems the notion of free
      energy density for equilibrium systems. Our exact expression for F is a nonlocal
      functional of rho, which yields the macroscopically long range correlations in
      the nonequilibrium steady state previously predicted by fluctuating hydrodynamics
      and observed experimentally.

PMID- 11580689
TI  - Decay of accelerated protons and the existence of the Fulling-Davies-Unruh
      effect.
AB  - We investigate the weak decay of uniformly accelerated protons in the context of
      standard quantum field theory. Because the mean proper lifetime of a particle is
      a scalar, the same value for this observable must be obtained in the inertial and
      coaccelerated frames. We are only able to achieve this equality by considering
      the Fulling-Davies-Unruh effect. This reflects the fact that the Fulling-Davies
      Unruh effect is mandatory for the consistency of quantum field theory.

PMID- 11580692
TI  - Fate of vector dominance in effective field theory.
AB  - We reveal the full phase structure of the effective field theory for QCD, based
      on hidden local symmetry (HLS) through the one-loop renormalization group
      equation including quadratic divergences. We then show that vector dominance (VD)
      is not a sacred discipline of the effective field theory but rather an accidental
      phenomenon peculiar to three-flavored QCD. In particular, the chiral symmetry
      restoration in the HLS model takes place in a wide phase boundary surface, on
      which the VD is nowhere realized. This suggests that VD may not be valid for
      chiral symmetry restoration in hot and/or dense QCD.

PMID- 11580693
TI  - Constructing parton convolution in effective field theory.
AB  - Parton convolution models have been used extensively in describing the sea quarks
      in the nucleon and explaining quark distributions in nuclei (the EMC effect).
      From the effective field theory point of view, we construct the parton
      convolution formalism which has been the underlying conception of all convolution
      models. We explain the significance of scheme and scale dependence of the
      auxiliary quantities such as the pion distributions in a nucleon. As an
      application, we calculate the complete leading nonanalytic chiral contribution to
      the isovector component of the nucleon sea.

PMID- 11580694
TI  - Lifetime of the 6793-keV state in 15O.
AB  - The energy derived from the CN cycle at low stellar temperatures is regulated by
      the 14N(p,gamma)15O reaction. A previous direct measurement of this reaction has
      been interpreted as showing evidence for a subthreshold resonance which makes a
      major contribution to the reaction rate at low temperatures. This resonance, at
      E(c.m.) = -504 keV would correspond to the known Ex = 6793-keV state in 15O. We
      have measured a mean lifetime of 1.60(+0.75)(-0.72) fs (90% C.L.) for this state
      using the Doppler-shift attenuation method. This lifetime is a factor of 15
      longer than that inferred from the (p,gamma) data and implies that the
      contribution of the subthreshold resonance is negligible.

PMID- 11580695
TI  - Ratiometric comparison of intense field ionization of atoms and diatomic
      molecules.
AB  - Intense-laser ionization rates for rare gas atoms and diatomic molecules have
      been precisely compared by making simultaneous measurements of ionization yield
      vs laser intensity for mixed atomic and molecular targets. At a given laser
      intensity, the N (2) and F (2) ionization yields are slightly greater than that
      of Ar. Conversely, comparison of O (2) and S (2) with Xe indicates significant
      ionization suppression in these molecules. Recent molecular ionization models
      that successfully describe ionization suppression in O (2) and its absence in N
      (2) fail to explain our observations in F (2) and S (2).

PMID- 11580696
TI  - Formation of K*He exciplexes on the surface of helium nanodroplets studied in
      real time.
AB  - Superfluid helium nanodroplets are doped with potassium atoms to form complexes
      with the alkali atom residing on the surface of the droplets. Dispersed laser
      induced fluorescence spectra of such systems already revealed the formation of
      M(*)He ( M = Na,K) exciplexes upon electronic excitation [Reho et al., Faraday
      Discuss. 108, 161 (1997)]. By means of femtosecond pump-probe spectroscopy, this
      formation process now is followed in real time. We find K(*)He(n = 1) to be
      formed within 180 fs. Furthermore, the existence of exciplexes with n>1 is
      quantified suggesting that the first ring around the potassium atom contains four
      helium atoms.

PMID- 11580697
TI  - Rayleigh instabilities in multiply charged sodium clusters.
AB  - The stability of multiply charged sodium clusters Na(q+)(n) (q< or =10) produced
      in collisions between neutral clusters and multiply charged ions A(z+) ( z = 1 to
      28) is experimentally investigated. Multiply charged clusters are formed within a
      large range of temperatures and fissilities. They are identified by means of a
      high-resolution reflectron-type time-of-flight mass spectrometer (m/deltam
      approximately 14 000). The maximum fissility of stable clusters is obtained for z
      = 28 and is X approximately 0.85+/-0.07, slightly below the Rayleigh limit (X =
      1). It is mainly limited by the initial cluster temperature (T approximately 100
      K).

PMID- 11580698
TI  - Observation of atomiclike electronic excitations in pure 3He and 4He clusters
      studied by fluorescence excitation spectroscopy.
AB  - The structure of the electronically excited states of 3He and 4He clusters is
      investigated using fluorescence excitation spectroscopy. Distinct bands are
      observed energetically close to atomic 1s-ns, nd, np transitions and attributed
      to perturbed excited He atomiclike states with different principle and orbital
      quantum numbers. The line shifts and widths of the bands of 3He and 4He clusters
      of the same size are different and correlate with the average particle density
      inside the clusters calculated using the density functional method.

PMID- 11580699
TI  - Electromagnetically induced transparency via adiabatic following of the
      nonabsorbing state.
AB  - It is shown that the adiabatic following of the dark, nonabsorbing state improves
      significantly the electromagnetically induced transparency performance and slows
      down the group velocity of the probe pulse. This concept can be used for fast
      selective gating of one pulse out of a pulse train.

PMID- 11580700
TI  - Photon localization in resonant media.
AB  - We report measurements of microwave transmission over the first five Mie
      resonances of alumina spheres randomly positioned in a waveguide. Though
      precipitous drops in transmission and sharp peaks in the photon transit time are
      found near all resonances, measurements of transmission fluctuations show that
      localization occurs only in a narrow frequency window above the first resonance.
      There the drop in the photon density of states is found to be more pronounced
      than the fall in the photon transit time above the resonance, leading to a
      minimum in the Thouless number.

PMID- 11580701
TI  - Experimental observation of revival structures in picosecond laser-induced
      alignment of I2.
AB  - We report the experimental observation of revival structures in the alignment of
      a ground-state rotational wave packet following nonresonant excitation of I2
      molecules by an intense picosecond laser pulse. The revivals appear at
      characteristic time delays following the excitation by the pump laser pulse, and
      show a significant narrowing of the angular distribution during a few
      picoseconds. The interaction with the pump laser also leads to a steady-state
      alignment of the molecule, due to rotational pumping.

PMID- 11580702
TI  - Experimental demonstration of anticipating synchronization in chaotic
      semiconductor lasers with optical feedback.
AB  - We report the first experimental observation of anticipating chaotic
      synchronization in an optical system using two diode lasers as transmitter and
      receiver. The transmitter laser is rendered chaotic by application of an optical
      feedback in an external-cavity configuration. It is found that the anticipation
      time does not depend on the external-cavity round trip time of the transmitter.

PMID- 11580703
TI  - Power-law behavior of power spectra in low Prandtl number Rayleigh-Benard
      convection.
AB  - The origin of the power-law decay measured in the power spectra of low Prandtl
      number Rayleigh-Benard convection near the onset of chaos is addressed using long
      time numerical simulations of the three-dimensional Boussinesq equations in
      cylindrical domains. The power law is found to arise from quasidiscontinuous
      changes in the slope of the time series of the heat transport associated with the
      nucleation of dislocation pairs and roll pinch-off events. For larger
      frequencies, the power spectra decay exponentially as expected for time
      continuous deterministic dynamics.

PMID- 11580704
TI  - Observation of stimulated electron-acoustic-wave scattering.
AB  - A diffraction-limited laser interacts with a plasma whose conditions are uniform
      on the scale of the focused laser spot. Two distinct, narrow waves are observed
      in the backscattered spectrum with phase velocities of v(phi)/v(e) = 1.4+/-0.08
      and 4.2+/-0.1, where v(e) is the electron thermal speed. The high-velocity wave
      is ordinary stimulated Raman scattering (SRS) from a Langmuir wave. The low
      velocity wave corresponds to stimulated scattering from an electron-acoustic wave
      (SEAS), and implies strong electron trapping. Previous SRS data from low-density
      plasmas are reinterpreted in terms of SEAS.

PMID- 11580705
TI  - Evolution of shell nonuniformities near peak compression of a spherical
      implosion.
AB  - The evolution of shell modulations near peak compression of direct-drive
      spherical-target implosions has been measured using the 60-beam, 30-kJ UV OMEGA
      laser system. The spatial size and amplitude of shell-areal-density modulations
      decrease during the target compression, then increase during its decompression as
      expected. The shell uniformity at peak compression has been increased by reducing
      single-beam, laser-drive nonuniformity.

PMID- 11580706
TI  - Fractal dimension of superfluid turbulence.
AB  - Superfluid turbulence consists of a disordered tangle of quantized vortex
      filaments which interact with each other and with the normal fluid. We develop a
      kinematic model of normal-fluid turbulence to study superfluid vortex tangles at
      finite temperatures and show by numerical simulation that the system of filaments
      has a fractal dimension larger than one. We find that the fractal dimension is
      directly related to the vortex-line density and is independent of temperature
      over a wide range.

PMID- 11580707
TI  - Quantitative analysis of x-ray absorption near edge structure data by a full
      multiple scattering procedure: the Fe-CO geometry in photolyzed carbonmonoxy
      myoglobin single crystal.
AB  - We report the first quantitative analysis of the Fe K-edge polarized x-ray
      absorption near edge structure of the iron protein carbonmonoxy-myoglobin (MbCO)
      single crystal and of its cryogenic photoproduct Mb(*)CO. The CO-Fe-heme local
      structure has been determined using a novel fitting procedure based on the full
      multiple scattering approach. The extracted local structure of Mb(*)CO includes a
      Fe-CO distance of (3.08+/-0.07) A, with a tilting angle between the heme normal
      and the Fe-C vector of (37+/-7) degrees, and a bending angle between the Fe-C
      vector and the C-O bond of (31+/-5) degrees.

PMID- 11580708
TI  - Effect of adsorbates on field emission from carbon nanotubes.
AB  - Recent experiments indicate that water molecules adsorbed on carbon nanotube tips
      significantly enhance field-emission current. Through first-principles density
      functional theory calculations we show that the water-nanotube interaction is
      weak in zero electric field. However, under emission conditions large electric
      field present at the tube tip: (a) increases the binding energy appreciably,
      thereby stabilizing the adsorbate; and (b) lowers the ionization potential (IP),
      thereby making it easier to extract electrons. Lowering of IP is enhanced further
      through the formation of a water cluster on the nanotube tip.

PMID- 11580709
TI  - Crystalline post-quartz phase in silica at high pressure.
AB  - alpha-quartz, which has been reported to undergo pressure-induced amorphization,
      was found to transform to a monoclinic, crystalline phase when compressed to 45
      GPa at room temperature in a close to hydrostatic, helium pressure medium. The x
      ray powder diffraction data obtained could be indexed based on a monoclinic cell,
      and the intensities are in agreement with a P2(1)/c model structure built up of
      3x2 zigzag chains of SiO6 octahedra. This new polymorph of silica, which is
      metastable under ambient conditions, has been isolated for the first time and is
      one of several possible competing dense forms containing octahedrally coordinated
      silicon.

PMID- 11580710
TI  - O2 diffusion in SiO2: triplet versus singlet.
AB  - We address the diffusion of the oxygen molecule in SiO2, using first-principles
      spin-polarized total-energy calculations. We find that the potential energy
      surfaces for the singlet and triplet states are very different in certain
      regions, and that the O2 molecule preserves its spin-triplet ground state not
      only at its most stable interstitial position inside the solid but also
      throughout its diffusion pathway. Therefore, the singlet state is not a good
      approximation to describe the behavior of O2 inside SiO2, and spin-polarization
      effects are fundamental to understand the properties of this system.

PMID- 11580690
TI  - Measurement of the decays B--> phiK and B--> phiK*.
AB  - We have observed the decays B--> phiK and phiK(*) in a sample of over 45 million
      B mesons collected with the BABAR detector at the PEP-II collider. The measured
      branching fractions are B(B+--> phiK+) = (7.7(+1.6)(-1.4)+/-0.8)x10(-6), B(B0-->
      phiK0) = (8.1(+3.1)(-2.5)+/-0.8)x10(-6), B(B+--> phiK(*+)) = (9.7(+4.2)(-3.4)+/
      1.7)x10(-6), and B(B0--> phiK(*0)) = (8.7(+2.5)(-2.1)+/-1.1)x10(-6). We also
      report the upper limit B(B+--> phipi(+))<1.4x10(-6) ( 90% C.L.).

PMID- 11580711
TI  - Facet growth under stress: the limits of strained-layer stability.
AB  - A crystal facet is metastable under stress, but the process of growth or
      sublimation roughens the facet and is expected to render it unstable. This poses
      a fundamental limit for heteroepitaxial growth of planar layers, e.g., in
      semiconductor devices. An analysis shows that this facet-growth instability can
      be suppressed to an arbitrary degree by growing slowly. Moreover, the local
      stress ("force dipole") inherent in atomic steps introduces a new, purely kinetic
      effect that dominates at low strain and can render planar growth dynamically
      stable.

PMID- 11580712
TI  - STM images apparently corresponding to a stable structure: considerable
      fluctuation of a phase boundary of the Si(111)-(square root of (3) x square root
      of (3))-Ag surface.
AB  - We study scanning tunneling microscopy (STM) images near a phase boundary of the
      Si(111)- (square root of (3) x square root of (3))-Ag surface by using Monte
      Carlo simulations based on results of first-principles calculations. The boundary
      is found to fluctuate from snapshot to snapshot, and the feature of the simulated
      STM images differs distinctly from the observed one with a straightly extending
      honeycomb pattern of bright spots. Remarkably, statistical averages of the
      simulated images reproduce the observed feature. This study gives a warning of
      our tendency to relate STM images revealing clear arrangement of bright spots
      with some stable structure.

PMID- 11580713
TI  - Molecular-scale density oscillations in water adjacent to a mica surface.
AB  - High-resolution specular x-ray reflectivity of the mica(001)-water interface
      under ambient conditions reveals oscillations in water oxygen density in the
      surface-normal direction, giving evidence of interfacial water ordering. The
      spacings between neighboring water layers in the near-surface, strongly
      oscillatory region are 2.5(2)-2.7(2) A, approximately the size of the water
      molecule. The density oscillations extend to about 10 A above the surface and do
      not strictly maintain a solvent-size periodicity as that in interfacial liquid
      metal and hard-sphere molecular liquids. We interpret this oscillatory density
      profile of the interfacial water as due to the "hard-wall" effect of the
      molecularly smooth mica surface.

PMID- 11580691
TI  - Measurement of branching fractions and search for CP-violating charge asymmetries
      in charmless two-body B decays into pions and kaons.
AB  - We present measurements, based on a sample of approximately 23x10(6) BB pairs, of
      the branching fractions and a search for CP-violating charge asymmetries in
      charmless hadronic decays of B mesons into two-body final states of kaons and
      pions. We find the branching fractions B(B0-->pi(+)pi(-)) = (4.1+/-1.0+/-0.7)x10(
      6), B(B0-->K+pi(-)) = (16.7+/-1.6+/-1.3)x10(-6), B(B+-->K+pi(0)) = (10.8(+2.1)(
      1.9)+/-1.0)x10(-6), B(B+-->K0pi(+)) = (18.2(+3.3)(-3.0)+/-2.0)x10(-6), B(B0-
      >K0pi(0)) = (8.2(+3.1)(-2.7)+/-1.2)x10(-6). We also report 90% confidence level
      upper limits for B meson decays to the pi(+)pi(0), K+K-, and K0K+ final states.
      In addition, charge asymmetries have been found to be consistent with zero, where
      the statistical precision is in the range of +/-0.10 to +/-0.18, depending on the
      decay mode.

PMID- 11580714
TI  - Anisotropic lattice distortions in random alloys from first-principles theory.
AB  - Within the framework of the exact muffin-tin orbitals (EMTO) theory we have
      developed a new method to calculate the total energy for random substitutional
      alloys. The problem of disorder is treated within the coherent potential
      approximation (CPA), and the total energy is obtained using the full charge
      density (FCD) technique. The FCD-EMTO-CPA method is suitable for determination of
      energy changes due to anisotropic lattice distortions in random alloys. In
      particular, we calculate the elastic constants of the Cu-rich face centered cubic
      Cu-Zn alloys ( alpha-brass) and optimize the c/a ratio for the hexagonal Zn-rich
      alloys for both the epsilon and eta phases.

PMID- 11580715
TI  - Exciton dispersion and electronic excitations in hcp 4He.
AB  - We present first measurements of the dispersion of excitons in solid helium,
      taken on a single hcp 4He crystal along the c axis. In agreement with studies on
      helium clusters, the major energy-loss peak can be interpreted as an intermediate
      molecular-type exciton, as we do not observe Wannier-like excitations. The
      measurements are in the (0 0 2) periodic zone, with the exciton energy dispersing
      along the c axis with a minimum at the gamma point. A calculated conduction band
      minimum at 31.0 eV above the valence band at gamma is supported by our data at
      energies above the exciton energy, leading to an exciton binding energy of 8.4
      eV.

PMID- 11580716
TI  - Probing interface electronic structure with overlayer quantum-well resonances:
      Al/Si(111).
AB  - The dispersion of quantum-well resonances in ultrathin epitaxial Al films on
      Si(111) reveals energy- and wave vector-dependent reflection properties at the
      Al/Si interface. The substrate electronic structure strongly influences the phase
      shift of the electron waves upon reflection at the interface. Thus the details of
      the substrate electronic structure need to be taken into account for a complete
      analysis of metallic quantum-well resonances. Furthermore, the assumption of loss
      of parallel wave vector information upon reflection or transmission through a
      lattice-mismatched interface is challenged. The changes induced in the electronic
      structure of the overlayer can be used to probe the ground-state substrate band
      edges.

PMID- 11580717
TI  - Kondo effect in quantum dots at high voltage: universality and scaling.
AB  - We examine the properties of a dc-biased quantum dot in the Coulomb blockade
      regime. For voltages V that are large compared to the Kondo temperature T(K), the
      physics is governed by the scales V and gamma, where gamma approximately
      V/ln(2)(V/T(K)) is the nonequilibrium decoherence rate induced by the voltage
      driven current. Based on scaling arguments, self-consistent perturbation theory,
      and perturbative renormalization group, we argue that due to the large gamma the
      system can be described by renormalized perturbation theory in 1/ln(V/T(K))<<1.
      However, in certain variants of the Kondo problem, two-channel Kondo physics is
      induced by a large voltage V.

PMID- 11580718
TI  - Kondo correlations and the Fano effect in closed Aharonov-Bohm interferometers.
AB  - We study the Fano-Kondo effect in a closed Aharonov-Bohm (AB) interferometer
      which contains a single-level quantum dot and predict a frequency doubling of the
      AB oscillations as a signature of Kondo-correlated states. Using the Keldysh
      formalism, the Friedel sum rule, and the numerical renormalization group, we
      calculate the exact zero-temperature linear conductance G as a function of the AB
      phase phi and level position epsilon. In the unitary limit, G(phi) reaches its
      maximum 2e(2)/h at phi = pi/2. We find a Fano-suppressed Kondo plateau for
      G(epsilon) similar to recent experiments.

PMID- 11580719
TI  - Disorder and transport in cuprates: weak localization and magnetic contributions.
AB  - We report resistivity measurements in underdoped YBa 2Cu3O6.6 and overdoped Tl
      2Ba2CuO6+x single crystals in which the concentration of defects in the CuO (2)
      planes is controlled by electron irradiation. Low T upturns of the resistivity
      are observed in both cases for large defect content. In the Tl compound the
      decrease of conductivity scales as expected from weak localization theory. On the
      contrary, in YBa 2Cu3O6.6 the much larger low T contribution to the resistivity
      is proportional to the defect content and might then be associated with a Kondo
      like spin flip scattering term. This would be consistent with the results on the
      magnetic properties induced by spinless defects.

PMID- 11580720
TI  - Evidence for two superconducting gaps in MgB2.
AB  - We have measured the Raman spectra of polycrystalline MgB2 from 25 to 1200 cm(
      1). A superconductivity-induced redistribution in the electronic Raman continuum
      was observed. Two pair-breaking peaks appear in the spectra, suggesting the
      presence of two superconducting gaps. The measured spectra were analyzed using a
      quasi-two-dimensional model in which two s-wave superconducting gaps open on two
      sheets of Fermi surface. For the gap values we have obtained Delta(1) = 22 cm(-1)
      ( 2.7 meV) and Delta(2) = 50 cm(-1) ( 6.2 meV). Our results suggest that a
      conventional phonon-mediated pairing mechanism occurs in the planar boron sigma
      bands and is responsible for the superconductivity of MgB2.

PMID- 11580721
TI  - Ordered valence-bond states in symmetric two-dimensional spin-orbital systems.
AB  - We consider a superexchange Hamiltonian, H = -SUM (<i,j>)(2S(i) . S(j)-(1/2))
      (2T(i) . T(j)-(1/2)), which describes systems with orbital degeneracy and strong
      electron-phonon coupling in the limit of large on-site repulsion. In an SU(4)
      Schwinger boson representation, a reduced spin-orbital interaction is derived
      exactly, and a mean field theory has been developed. In one dimension, a spin
      orbital liquid state with a finite gap is obtained. On a two-dimensional square
      lattice a novel type of spin-orbital ferromagnetically ordered state appears,
      while spin and orbital are antiferromagnetic. An important relation has been
      found, relating the spin and orbital correlation functions to the combined spin
      orbital ones.

PMID- 11580722
TI  - Metallic-type oscillatory interlayer exchange coupling across an epitaxial FeSi
      spacer.
AB  - We study interlayer exchange coupling in epitaxial Fe/Fe(0.56)Si(0.44)/Fe
      trilayers. Iron-silicide spacers with high structural and compositional
      homogeneity for thicknesses up to 34 A are grown by coevaporation from two
      electron-beam sources. The coupling strength oscillates with spacer thickness for
      temperatures from 20 to 300 K with two antiferromagnetic maxima at 12 and 26 A,
      and it clearly increases with decreasing temperature down to 80 K. We conclude
      that the coupling across ordered Fe(1-x)Si(x) ( x approximately 0.5) is described
      by the conventional theory of interlayer coupling across metallic spacers.

PMID- 11580723
TI  - Anisotropic magnetocaloric effect in nanostructured magnetic clusters.
AB  - We report the first experimental observation of anisotropic magnetocaloric effect
      (MCE) in the Fe8 clusters. It is found that the magnetic anisotropy plays a very
      important role in the determination of the magnetocaloric effect. The maximum and
      minimum MCE's are observed when the applied magnetic fields are parallel and
      perpendicular to the easy axis, respectively. The quantum spin Hamiltonian of a
      Fe8 cluster is used to calculate the partition function and the magnetization in
      a range of temperature and magnetic field. Excellent quantitative agreement
      between the experimental data and calculation is observed.

PMID- 11580724
TI  - Point defects, ferromagnetism, and transport in calcium hexaboride.
AB  - The formation energy and local magnetic moment of a series of point defects in
      CaB6 are computed using a supercell approach within the generalized gradient
      approximation to density functional theory. It is found that the substitution of
      Ca by La does not lead to the formation of a local moment, while a neutral B6
      vacancy carries a moment of 2.4 Bohr magnetons. A plausible mechanism for the
      ferromagnetic ordering of these moments is suggested. Since the same broken B-B
      bonds appear on the preferred (100) cleavage planes of the CaB6 structure, it is
      argued that internal surfaces in polycrystals as well as external surfaces in
      general will make a large contribution to the observed magnetization.

PMID- 11580725
TI  - Ultralong dephasing time in InGaAs quantum dots.
AB  - We measure a dephasing time of several hundred picoseconds at low temperature in
      the ground-state transition of strongly confined InGaAs quantum dots, using a
      highly sensitive four-wave mixing technique. Between 7 and 100 K the polarization
      decay has two distinct components resulting in a non-Lorentzian line shape with a
      lifetime-limited zero-phonon line and a broadband from elastic exciton-acoustic
      phonon interactions.

PMID- 11580726
TI  - Raft instability of biopolymer gels.
AB  - Following recent x-ray diffraction experiments by Wong, Li, and Safinya on
      biopolymer gels, we apply Onsager excluded volume theory to a nematic mixture of
      rigid rods and strong " pi/2" cross-linkers obtaining a long-ranged, highly
      anisotropic depletion attraction between the linkers. This attraction leads to
      breakdown of the percolation theory for this class of gels, to breakdown of
      Onsager's second-order virial method, and to formation of heterogeneities in the
      form of raftlike ribbons.

PMID- 11580727
TI  - Swarming ring patterns in bacterial colonies exposed to ultraviolet radiation.
AB  - We report a novel morphological transition in a Bacillus subtilis colony
      initially growing under ambient conditions, after ultraviolet radiation exposure.
      The bacteria in the central regions of the colonies are observed to migrate
      towards the colony edge forming a ring during uniform spatial exposure. When the
      radiation is switched off, the colonies were observed to grow both inward into
      the evacuated regions as well as outward indicating that the pattern is not
      formed due to depletion of nutrients at the center of the colony. We also propose
      a reaction-diffusion model in which waste-limited chemotaxis initiated by the UV
      radiation leads to the observed phenomenology.

PMID- 11580729
TI  - Tubal ligation reduces the risk of ovarian cancer.

PMID- 11580728
TI  - Observation of stimulated emission at high gyroharmonics: basis for a synchrotron
      resonance maser.
AB  - First experimental observations are reported on stimulated coherent synchrotron
      radiation from highly relativistic electrons in a strong magnetic field. The
      experiment employed a quasioptical millimeter-wave resonator and a 6-MeV electron
      beam gyrating in a field of up to 25 kG. Coherent radiation at 54 GHz,
      corresponding to the 11th gyroharmonic, was observed and characterized. These
      observations demonstrate the possibility of a synchrotron resonance maser.

PMID- 11580730
TI  - Human albumin is effective in prevention of severe OHSS.
AB  - Severe OHSS is an iatrogenic, potentially life-threatening complication of
      controlled ovarian hyperstimulation. Intravenous human albumin, administered
      around the time of oocyte retrieval has been claimed to prevent development of
      this serious event. It was hypothesized that albumin acts through its osmotic
      pressure and through the binding and inactivation, at a critical time of the
      cycle, of an hCG-mediated factor secreted by the corpora lutea, that impedes
      capillary integrity and leads to the development of OHSS. The present article
      evaluates the available evidence in the medical literature whether albumin is
      effective in reducing the risk of severe OHSS. Several trials have been
      identified, most of them were retrospective and few were prospective randomized
      controlled trials. Although albumin prophylaxis cannot offer absolute protection,
      all three randomized placebo-controlled trials, that have been published so far,
      demonstrated a significant reduction in the incidence of severe OHSS.

PMID- 11580731
TI  - Vaginal palpation of pelvic floor muscle strength: inter-test reproducibility and
      comparison between palpation and vaginal squeeze pressure.
AB  - BACKGROUND: Vaginal palpation is commonly used in clinical practice to teach and
      evaluate pelvic floor muscle strength, and several grading systems have been
      developed. The aim of the present study was to test inter-rater reproducibility
      of the modified Oxford grading system and compare results from vaginal palpation
      with squeeze pressure measurement. METHODS: Twenty female physical therapy
      students, mean age 25.1 years (range 21-38) participated in the study. Two
      experienced physical therapists conducted the palpation test in random order.
      Muscle strength was classified according to a 6-point scale (modified Oxford
      grading system). Results from the palpation test were compared with measurement
      of vaginal squeeze pressure using a vaginal balloon connected to a fiberoptic
      microtransducer (Camtech AS, Sandvika, Norway). To ensure validity of pressure
      measurement only contractions with simultaneous observation of inward movement of
      the perineum were registered. RESULTS: The inter-rater reliability for vaginal
      palpation was 0.70 measured by Spearman's rho (p<0.01). Cohen's Kappa was
      kappa=0.37 (SEM 0.16). There was agreement between the physical therapists in
      nine subjects (45%). In all but one subject the disagreement was one category.
      Mean maximal strength for the group was 19.7 cm H2O (95% CI: 16.5-22.9). There
      were no differences between weak, moderate, good and strong muscle contraction
      classified by palpation test when comparing results from the vaginal squeeze
      pressure (p=0.66). CONCLUSIONS: Vaginal palpation is mandatory when teaching
      correct pelvic floor muscle contraction. However, the present results indicate
      that the method is not reproducible, sensitive and valid to measure PFM strength
      for scientific purposes.

PMID- 11580732
TI  - Renal biopsy in pregnancies complicated by undetermined renal disease.
AB  - BACKGROUND: The aim of this retrospective study was to verify the role of renal
      biopsy in pregnancies complicated by renal dysfunction. METHODS: A series of 15
      percutaneous renal biopsies performed in 15 pregnant women with renal disease
      presenting during pregnancy over the past 10 years (1990-1999) were reviewed.
      RESULTS: All the patients underwent renal biopsy before 30 weeks of gestation.
      The indications for renal biopsy were renal dysfunction of unknown cause or
      symptomatic nephrotic syndrome (NS). Patients with toxemia were excluded. Eight
      women had lupus nephritis, including five with diffuse crescenteric changes and
      three with a mesangial proliferative pattern. Three had chronic
      glomerulonephritis (CGN), two had mesangial proliferative glomerulonephritis and
      one each had diabetic nephrosclerosis and endocapillary proliferative
      glomerulonephritis. There were no significant complications except in one patient
      who experienced gross hematuria. Early induction of labor was recommended for the
      four patients with diabetic nephrosclerosis or CGM. The other 11 patients
      received intravenous pulse methylprednisolone or high dose oral prednisolone
      therapy. The responses to steroid therapy in these 11 patients were as follows:
      five achieved complete remission of NS, three achieved incomplete remission, and
      three achieved partial remission. After 2 years' follow-up, seven mothers
      achieved complete remission, three had died, three developed chronic renal
      failure (CRF), and two progressed to end stage renal failure (ESRF) requiring
      chronic hemodialysis. Fourteen of the 15 pregnancies resulted in live births and
      the other child was stillborn. CONCLUSIONS: Renal biopsy performed during
      pregnancy is not contraindicated. The results of histopathological studies are
      extremely useful in counseling regarding continuation or termination of
      pregnancy, potential maternal and fetal outcome, and recommending specific
      therapeutic modalities.

PMID- 11580733
TI  - Smoking, sex of the offspring, and risk of placental abruption, placenta previa,
      and preeclampsia: a population-based cohort study.
AB  - BACKGROUND: : Placental abruption, placenta previa, and preeclampsia are serious
      pregnancy complications with an increased risk of perinatal death. Smoking during
      pregnancy is associated with increased risk of abruption and placenta previa, and
      it reduces the risk of preeclampsia. We examined the association between mothers'
      smoking habits during pregnancy, taking the sex of the offspring into
      consideration, and the risk and prognosis of placental abruption, placenta
      previa, and preeclampsia METHODS: : We conducted the study in the County of North
      Jutland, Denmark. Using the 10-digit personal identification number given to
      every Danish citizen at birth, we linked data from the Danish Medical Birth
      Registry, including information on mother and child, to data from the Pharmaco
      Epidemiological Prescription Database with data on all reimbursed prescriptions
      to use selected drugs as a proxy measure for some maternal diseases, and data
      from the Regional Hospital Discharge Registry, including the discharge diagnoses.
      Among 47,932 singleton births we included only births for which we had
      information about the mothers' smoking habits, leaving 46,313 births for
      analysis. RESULTS: : Smoking was associated with the risk of placental abruption
      (OR=1.99 (95% CI 1.72-2.30)) and placenta previa (OR=1.88 (95% CI 1.15-3.07)).
      Smoking was inversely associated with the risk of preeclampsia (OR=0.55 (95% CI
      0.48-0.62)). After stratification for the sex of the offspring the risk estimate
      of smoking as risk factor for placenta previa decreased for male fetuses (OR=1.63
      (95% CI 0.75-3.51)) and increased for female fetuses (OR=4.82 (95% CI 1.69
      13.75)). CONCLUSION: : Female fetuses are more vulnerable than male to the
      negative effect of maternal smoking on placenta previa.

PMID- 11580734
TI  - Perinatal complications in women with gestational diabetes mellitus.
AB  - BACKGROUND: The aim of the study was to examine the outcome of the pregnancy and
      neonatal period in 1) women with gestational diabetes mellitus and non-diabetic
      pregnant women, and 2) in women with early and late diagnosis of gestational
      diabetes mellitus. METHODS: Included were 327 women with gestational diabetes
      mellitus and 295 non-diabetic women, who were screened with a 75 g oral glucose
      tolerance test because of risk factors for gestational diabetes. Women with
      gestational diabetes mellitus were treated with low-caloric diet and insulin when
      appropriate, while women in the control group received routine antenatal care.
      RESULTS: Gestational age at delivery was significantly lower in the group with
      gestational diabetes mellitus, both when considering all deliveries (39.1+/-1.7
      weeks versus 39.8+/-2.0 weeks, p<0.05) and only those with spontaneous onset of
      labor (38.8+/-2.0 weeks versus 40.0+/-1.6 weeks, p<0.05). The frequency of
      macrosomia was increased, although not statistically significant (8% vs. 2%,
      p=0.07), and the rate of admission to the neonatal ward was significantly
      increased (18% vs. 9%, p<0.05) in the group with gestational diabetes. Women with
      early diagnosis of gestational diabetes mellitus had a significantly increased
      need for insulin treatment during pregnancy (36% vs. 9% p<0.05) and a
      significantly higher occurrence of diabetes mellitus at follow-up from two months
      until three years postpartum. CONCLUSIONS: This study of women with gestational
      diabetes mellitus and non-diabetic pregnant women showed that gestational
      diabetes mellitus was associated with a significantly lower gestational age at
      delivery and an increased rate of admission to the neonatal ward. Women diagnosed
      with GDM before 20 weeks of gestation had an increased need for insulin treatment
      during pregnancy and a high risk of subsequent overt DM, compared with women
      diagnosed with GDM later in pregnancy.

PMID- 11580735
TI  - Do very sick neonates born at term have antenatal risks? 1. Infants ventilated
      primarily for problems of adaptation to extra-uterine life.
AB  - AIMS: 1. Ascertain antenatal and intrapartum risk factors for term neonates
      ventilated primarily for 'perinatal asphyxia'. 2. Describe the neonatal morbidity
      and mortality. METHODS: Population-based case control cohort study. SETTING:
      Sydney and four large rural/urban health areas in New South Wales. SUBJECTS:
      Singleton term infants, no major congenital anomaly: subset of 83 infants
      ventilated primarily for 'asphyxia' from 182 cases admitted to a tertiary
      neonatal intensive care unit (NICU) for mechanical ventilation, 550 randomly
      selected controls. Outcome. Risk factors for case status by maternal, antenatal,
      labor, delivery, and combined epochs, adjusted odds ratios (OR), 95 per cent
      confidence intervals (CI), p < 0.05. RESULTS: Predictors of case status by
      multivariate epochs: Primigravida (1.8 [1.1, 2.8]), thyroid disease (7.8 [1.1,
      57.0]), any antenatal complication (5.1 [3.0, 8.6]), growth restriction (4.2
      [1.7, 10.4]), male gender (2.1 [1.3, 3.5]), gestational age >40 weeks (1.9 (1.1,
      3.3)), prolonged rupture of membranes (9.7 [1.3, 72.5]), complicated labor (6.6
      [3.7, 11.9]), induced labor (2.2 [1.3, 3.9]), prostaglandins 2.46 [1.23, 4.91]),
      maternal pyrexia (10.8 [2.8, 42.7]), placental hemorrhage in labor (OR 4.24
      [1.45, 12.42]), forceps delivery (4.1 [1.9, 8.5]), emergency cesarean section
      (4.7 [2.6, 8.7]). Twenty case infants (24%) and no control infants died.
      CONCLUSIONS: This study has shown maternal and antepartum risk factors for severe
      neonatal morbidity in term infants. More centers need to become interested in the
      term baby, so that a larger multicenter study can further elucidate the
      heterogeneous causal pathways to term neonatal morbidity.

PMID- 11580736
TI  - Do very sick neonates born at term have antenatal risks? 2. Infants ventilated
      primarily for lung disease.
AB  - AIMS: 1. Ascertain antenatal and intrapartum risk factors for term neonates
      ventilated primarily for respiratory problems. 2. Describe the neonatal morbidity
      and mortality. METHODS: Population-based case control cohort study. SETTING:
      Sydney and four large rural/urban Health Areas in New South Wales, 1996.
      SUBJECTS: Singleton term infants, no major congenital anomaly: subset of 99
      infants ventilated primarily for respiratory problems from 182 cases admitted to
      a tertiary neonatal intensive care unit (NICU) for mechanical ventilation, and
      550 randomly selected controls. OUTCOME: Risk factors for case status by
      maternal, antenatal, labor, delivery, and combined epochs, adjusted Odds Ratios
      (OR), 95 per cent Confidence Intervals (CI), p<0.05. RESULTS: Predictors of case
      status by multivariate epochs: mother's age > or =35 years (1.9 (1.1, 3.2)
      p=0.03), primigravida (1.8 (1.1, 2.8) p=0.01), any antenatal complication (3.8
      (2.4, 5.9) p=0.0001), birth weight < 3rd percentile (3.7 (1.5, 9.1) p=0.006),
      gestational diabetes (2.9 (1.3, 6.9) p=0.01), maternal pyrexia (6.5 (1.6, 27.2)
      p=0.01), birth weight >90th percentile (1.8 (1.01, 3.2) p=0.047), gestation 37-38
      weeks (2.3 (1.5, 3.6) p=0.0004), forceps (4.4 (2.1, 9.1) p=0.0001), elective
      cesarean section (3.7 (2.0, 6.5) p=0.0001), emergency cesarean section (4.5 (2.4,
      8.4) p=0.0001). Case mortality rate was 5 per cent. CONCLUSION: The pathways to
      neonatal respiratory morbidity in term infants are multifactorial. Several areas
      which warrant more in-depth study are: elective cesarean section at 37-38 weeks
      gestation, fetal growth restriction, macrosomia and the pattern of in-utero
      growth, maternal weight gain during pregnancy, gestational diabetes, pyrexia in
      labor and the role of chorioamnionitis.

PMID- 11580737
TI  - Maternal smoking and gestational age in twin pregnancies.
AB  - BACKGROUND: A twin pregnancy imposes greater demands on maternal physiology and
      smoking may thus be associated theoretically with a greater risk of preterm
      delivery than in singleton pregnancies. POPULATION AND METHODS: From 1989 to 1996
      all women who booked for antenatal care at the Department of Gynecology and
      Obstetrics, Aarhus University Hospital, Denmark were asked to fill in two
      questionnaires. Apart from smoking habits, these questionnaires provided
      information on medical and obstetric history together with information on
      sociodemographic and other lifestyle variables. Gestational age at delivery was
      calculated from ultrasonographically determined fetal biparietal diameter and
      information about the last menstrual period. Only women carrying twins were
      included in the present study (n=401). RESULTS: Mean gestational age was 5 days
      (95% CI 1-9 days) shorter among smokers compared with non-smokers. Among non
      smokers mean gestational age was 261 days (+/-18), among women who smoked 1-9 and
      10+ cigarettes per day 257 days (+/-23) and 255 days (+/-20), respectively. The
      overall risk of preterm delivery (< 37 weeks) and delivery before 34 completed
      weeks was 1.3 (95% CI 0.9-2.2) and 1.4 (95% CI 0.8-2.4), respectively.
      Primiparous women had shorter gestational age than did multiparous women. Still,
      among primiparous as well as among multiparous women gestational age decreased
      with smoking. Adjustment for maternal age, height and prepregnancy weight,
      alcohol and caffeine intake, marital status, education, occupational status,
      preterm birth in previous pregnancies, and in vitro fertilization in the present
      pregnancy did not change the results. CONCLUSIONS: Smoking has a substantial
      effect on mean gestational age in twin pregnancies, and a dose response like
      relationship is present.

PMID- 11580738
TI  - An increasing proportion of infants weigh more than 4000 grams at birth.
AB  - BACKGROUND: To investigate how mean birthweight has changed in the past decade,
      and to describe changes in the proportion of infants with a birthweight above
      4000 grams (g). METHODS: We analyzed data on 43,561 singleton infants born
      between 1990 and 1999 at Aarhus University Hospital, Denmark. Information on
      birthweight, gestational age, stillbirths, malformations, mode of delivery,
      prelabor intervention, and maternal diabetes was obtained from birth registration
      forms. RESULTS: For all infants mean birthweight increased by 45 g (95% CI: 20-70
      g) from 3474 g in 1990 to 3519 g in 1999. For infants born at term the mean
      increase was 62 g (95% CI: 41-83 g). During the same period the percentage of
      infants born with a birthweight above 4000 g increased from 16.7% in 1990 to
      20.0% in 1999 (p<0.05). Simultaneously we found a decrease in gestational age and
      an increase in the frequency of induction of labor. There was a statistically
      significantly higher risk of giving birth to an infant with a birthweight above
      4000 g throughout the decade, when gestational age and prelabor intervention was
      taken into account. CONCLUSIONS: In Denmark mean birthweight has risen during the
      past decade independently of gestational age and prelabor intervention.
      Simultaneously the risk of having a baby with a birthweight above 4000 g has
      increased. Further studies on potential risk factors for birth of large infants
      are needed.

PMID- 11580739
TI  - IVF treatments and their outcomes in Finland in the 1990s.
AB  - BACKGROUND: In vitro fertilization and its variants have become routine
      infertility treatments in industrialized countries. Our purpose is to summarize
      the procedures and treatment outcomes in Finland in the 1990s and to compare the
      results between public and private clinics. METHODS: The data came from the
      Finnish IVF statistics for 1992 to 1999. Most analyses were done for the years
      1994 to 1998 for which identical data-collection sheets were used. RESULTS: In
      1999, 12 of the 19 clinics offering assisted reproductive treatments were
      private. The number of treatments increased from 2,331 in 1992 to 7,213 in 1999.
      In total 58% were performed in the private sector. Most treatments were given for
      women aged 30 to 39 years, but in the private sector women were up to on average
      two years older. Most often care was given due to tubal factor or unexplained
      infertility (IVF) and due to male factor or multiple causes (ICSI). The number of
      transferred embryos decreased during the study period, but the transfer of two
      embryos was still most frequent. Three out of four IVF and ICSI pregnancies, and
      two out of three FET pregnancies ended in a live birth. The success rates
      improved for IVF and for ICSI after adjustment for the number of transferred
      embryos, but not for FET. Small but inconsistent differences were observed in the
      success rates between the private and public sectors. There was noticeable
      variation between clinics. CONCLUSION: The number of treatment cycles stabilized
      in the late 1990s. The success rates improved only slightly and the differences
      in outcome measures between private and public clinics were small. However,
      neither this nor the large clinical variation could be investigated more
      thoroughly without collecting individual register data.

PMID- 11580740
TI  - Does mode of hysterectomy influence micturition and defecation?
AB  - OBJECTIVE: Hysterectomy may affect bladder and bowel function. A retrospective
      study was performed to compare the prevalence of micturition and defecation
      symptoms between different modes of hysterectomy. METHODS: All pre-operatively
      asymptomatic patients, with uteral size < or =10 cm, who underwent hysterectomy
      between 1988 and 1997 were interviewed about the prevalence of micturition and
      defecation symptoms and the experienced physical and emotional limitations of
      these symptoms. Using logistic regression analysis, odds ratios (OR) were
      calculated for all symptoms of which the prevalence between modes of hysterectomy
      differed more than 10%. These odds ratios were adjusted for differences in other
      prognostic factors. RESULTS: Vaginal hysterectomy was performed on 68 patients,
      total abdominal hysterectomy on 109 patients and subtotal abdominal hysterectomy
      on 50 patients. An increased prevalence of urge incontinence (adjusted OR 1.5
      (95% CI 0.8-3.1)) and feeling of incomplete evacuation (adjusted OR 1.9 (95% CI
      1.0-4.0)) was observed among patients who had undergone vaginal hysterectomy as
      compared to patients who had undergone total abdominal hysterectomy. The
      prevalence of urge incontinence (adjusted OR 1.8 (95% CI 0.8-4.2)) and difficulty
      emptying the rectum (adjusted OR 1.8 (95% CI 0.7-4.4)) was higher among patients
      who had undergone vaginal hysterectomy than among patients who had undergone
      subtotal abdominal hysterectomy. Statistically significant odds ratios were not
      observed. Relevant differences in physical and emotional limitations related to
      micturition and defecation symptoms were not observed between groups. CONCLUSION:
      Our results suggest that technique of hysterectomy may influence the prevalence
      of micturition and defecation symptoms following hysterectomy.

PMID- 11580741
TI  - Do fertile women remember the onset of stress incontinence? Recall bias 5 years
      after 1st delivery.
AB  - BACKGROUND: To evaluate fertile women's ability to recall the onset of stress
      incontinence. METHODS: In a prospective cohort study 305 primiparae were
      interviewed after 1st delivery and again 5 years later using a tested
      questionnaire. In 83 women with stress incontinence 5 years after 1st delivery
      history of onset was compared with data from the initial questionnaire by
      grouping women with onset before 1st pregnancy, during 1st pregnancy, during 1st
      puerperium or after 1st puerperium. RESULTS: Five years after 1st delivery only
      26% recalled the onset of stress incontinence precisely. The statistical
      agreement for each of the four groups of women with different recall of onset
      varied with a Kappa from 0.02 to 0.38. CONCLUSION: Five years after 1st delivery
      stress incontinent women seem to recall the onset of the symptom imprecisely.

PMID- 11580742
TI  - Randomized double-blind study evaluating the efficacy on uterine fibroids
      shrinkage and on intra-operative blood loss of different length of leuprolide
      acetate depot treatment before myomectomy.
AB  - OBJECT: To determine whether length of pre-operative treatment with gonadotrophin
      releasing hormone agonists (GnRHa) may have different effects on uterine
      shrinkage and intra-operative blood loss, 36 patients with symptomatic uterine
      fibroids awaiting myomectomy were randomly divided into two groups. METHOD:
      Twenty patients received long-term GnRHa administration, six monthly depot
      injections of leuprolide acetate (LA), while 16 patients were treated with two
      monthly LA injections before surgery. The hemoglobin concentration and estradiol,
      follicle-stimulating hormone and luteinizing hormone concentrations were measured
      before and after treatment in both groups. RESULTS: Uterine volume decreased in
      the long-term treated group from 680+/-276 cm3 to 486+/-195 cm3 (36%) after two
      and to 388+/-172 cm3 (51%) after six LA injections. In the short-term treated
      group the basal uterine volume decreased from 745+/-320 cm3 to 456+/-177 cm3
      (39%) after two LA injections. The uterine volume decrease was statistically
      significant (p<0.05) after two LA injections in both groups while the decrease
      observed between two and six LA injections was not significant (p>0.05). The
      intra-operative blood-loss was not significantly different between the two groups
      studied, 315+/-93 cm3 and 336+/-88 cm3. CONCLUSION: Two pre-operative GnRHa depot
      injections offer similar results, in terms of uterine shrinkage and intra
      operative blood loss, and a longer treatment seems to be justified in cases of
      anemia.

PMID- 11580743
TI  - Comparison of Endorette and dilatation and curettage for sampling of the
      endometrium in women with postmenopausal bleeding.
AB  - MAIN QUESTION: To compare the diagnostic properties of Endorette and D&C in women
      with postmenopausal bleeding, to relate the properties to endometrial thickness
      as measured by ultrasound, and to assess the women's experiences of the two
      methods. METHODS: In a prospective study, 133 consecutive women with
      postmenopausal bleeding were examined with transvaginal ultrasound. After
      measuring the endometrial thickness, Endorette sampling was performed without
      anesthesia. Dilatation and curettage (D&C) was carried out under general
      anesthesia within six weeks. After completion of each sampling procedure the
      women filled in a questionnaire regarding their experience of the sampling.
      RESULTS: Endorette sampling failed in 16% (21/133) of the women. More than half
      (56%) of the women experienced moderate or strong pain during Endorette sampling,
      and the doctor underestimated the pain in 62% of the women. Endorette failed to
      diagnose two of seven (29%) endometrial cancers found at D&C. In one of these two
      cases, the examiner suspected that the Endorette device had not reached the
      uterine fundus. In women with endometrium < 7 mm, Endorette and D&C showed
      similar results with regard to obtaining a sufficient endometrial sample and to
      distinguishing normal endometrium, benign pathological endometrium and
      malignancy. In women with endometrium > or =7 mm, Endorette yielded insufficient
      samples significantly more often than D&C (23% vs 6%, p=0.02; the McNemar test)
      and missed all polyps and most (77%) hyperplasias diagnosed by D&C. CONCLUSION:
      Endorette and D&C have similar diagnostic properties in women with postmenopausal
      bleeding and endometrium < 7 mm. D&C is superior to Endorette in women with
      endometrium > or =7 mm.

PMID- 11580744
TI  - Large placental chorioangioma.

PMID- 11580745
TI  - Chromophobe renal cell carcinoma in pregnancy: case report and review of the
      literature.

PMID- 11580746
TI  - Giant breast cyst: a rare but distinct entity.

PMID- 11580747
TI  - Substantial relief of myopathic disability by progesterone therapy.

PMID- 11580748
TI  - Double survival despite cord intertwining in monoamniotic twins.

PMID- 11580749
TI  - Use of the hemostatic multiple square suturing of the uterus for control of
      massive postcesarean section hemorrhage and preservation of fertility.

PMID- 11580750
TI  - Disturbance of endothelial barrier function by bacterial toxins and atherogenic
      mediators: a role for Rho/Rho kinase.

PMID- 11580751
TI  - Electron microscopy applications for quantitative cellular microbiology.
AB  - Recently, there has been a surge of interest in analysing intracellular
      trafficking of pathogenic microorganisms. This field relies heavily on a wide
      range of approaches developed by cell biologists. However, one well-established
      approach that seems to be underused in cellular microbiology is electron
      microscopy (EM). In this article, we emphasize the power of state-of-the-art EM
      approaches, especially when used in conjunction with the quantitative approaches
      provided by stereology. Together, this combination of techniques can be exploited
      to pursue kinetic analyses of the intracellular pathways followed by
      microorganisms. In addition, it will provide a more detailed description of the
      antigenic composition of relevant structures than is possible by light microscopy
      (LM). Here, we will explain how EM, applied in an integrated approach with LM,
      has distinct advantages and can provide unique insights into the cellular fate of
      microorganisms.

PMID- 11580752
TI  - Characterization of translocation pores inserted into plasma membranes by type
      III-secreted Esp proteins of enteropathogenic Escherichia coli.
AB  - Many mucosal pathogens use type III secretion systems for the injection of
      effector proteins into target cells. The type III-secreted proteins EspB and EspD
      of enteropathogenic Escherichia coli (EPEC) are inserted into the target cell
      membrane. Together with EspA, these proteins are supposed to constitute a
      molecular syringe, channelling other effector proteins into the host cell. In
      this model, EspB and EspD would represent the tip of the needle forming a pore
      into target cell membranes. Although contact-dependent and Esp-mediated
      haemolytic activity by EPEC has already been described, the formation of a
      putative pore resulting in haemolysis has not been demonstrated so far. Here, we
      show that (i) diffusely adhering (DA)-EPEC strains exhibit a type III-dependent
      haemolytic activity too; (ii) this activity resides in the secreted proteins and,
      for DA-EPEC strains, in contrast to EPEC strains, does not require bacterial
      contact; and (iii) pores are introduced into the target cell membrane.
      Osmoprotection revealed a minimal pore size of 3-5 nm. The pores induced by type
      III-secreted proteins of DA-EPEC were characterized by electron microscopy
      techniques. Analysis by atomic force microscopy demonstrated the pores to be
      composed of six to eight subunits with a lateral extension of 55-65 nm and to be
      raised 15-20 nm above the membrane plane. We could also demonstrate an
      association of EspB and EspD with erythrocyte membranes and an interaction of
      both proteins with each other in vitro. These results, together with the
      homologies of EspB and EspD to proposed functional domains of other pore-forming
      proteins (Yop/Ipa), strongly support the idea that both proteins are directly
      involved in pore formation, which might represent the type III secretion system
      translocon.

PMID- 11580753
TI  - CEACAM is not necessary for Neisseria gonorrhoeae to adhere to and invade female
      genital epithelial cells.
AB  - Neisseria gonorrhoeae has a repertoire of up to 11 opacity-associated (Opa)
      proteins that are adhesins. Most Opa proteins adhere to CEACAM antigens and when
      CEACAM molecules are present on the surface of transfected epithelial cells their
      binding by Opa is thought to induce invasion of these cells by gonococci. In this
      study, we investigated whether several malignant epithelial cell lines, normal
      cervical and fallopian tube epithelial cell cultures, as well as normal fallopian
      tube tissue express several of the CEACAM molecules, and whether gonococci use
      these molecules for adherence and invasion of these female genital epithelial
      cells. A primary cervical cell culture and metastatic cervical cell line ME180
      both expressed CEACAM as shown by whole cell ELISA and flow cytometry, and
      increased the surface expression of total CEACAM during incubation with Opa+
      gonococci. Opa+ gonococci both adhered to and invaded these cells; CEACAM
      specific monoclonal antibody (MAb) partially abolished this interaction. Two
      primary fallopian epithelial tube cell cultures, a primary cervical cell culture
      and two malignant cell lines, HEC-1-B and HeLa, did not express CEACAM nor was
      CEACAM mRNA present. No evidence of either intracellular or secreted
      extracellular CEACAM was found with HEC-1-B and HeLa cells. Opa+ gonococci both
      adhered to and invaded CEACAM non-expressing cells; however, Opa+ gonococcal
      association with these non-expressing cell lines could not be inhibited with
      CEACAM-specific MAb. These data show that CEACAM is not always expressed on
      female genital epithelial cells and is not essential for gonococcal adherence and
      invasion. However, when CEACAM is expressed, Opa+ gonococci exploit it for the
      adherence to and invasion of these cells.

PMID- 11580754
TI  - Yersinia enterocolitica invasin triggers phagocytosis via beta1 integrins,
      CDC42Hs and WASp in macrophages.
AB  - The Yersinia outer surface protein invasin binds to beta1 integrins on target
      cells and has been shown to trigger phagocytic uptake by macrophages. Here, we
      investigated the role of the actin regulator Wiskott-Aldrich syndrome protein
      (WASp), its effector the Arp2/3 complex and the Rho-GTPases CDC42Hs, Rac and Rho
      in invasin/beta1 integrin-triggered phagocytosis. During uptake of invasin-coated
      latex beads, the alpha5beta1 integrin, WASp and the Arp2/3 complex were recruited
      to the developing actin-rich phagocytic cups in primary human macrophages.
      Blockage of beta1 integrins by specific antibodies, inhibition of Arp2/3 function
      by microinjection of inhibitors or the use of WASp knockout macrophages inhibited
      phagocytic cup formation and uptake. Furthermore, microinjection of the dominant
      negative GTPase mutants N17CDC42Hs, N17Rac or the Rho-specific inhibitor C3
      transferase into macrophages greatly attenuated invasin-induced formation of
      cups. These data suggest that during invasin-triggered phagocytosis beta1
      integrins activate actin polymerization via CDC42Hs, its effector WASp and the
      Arp2/3 complex. The contribution of Rac and Rho to phagocytic cup formation also
      suggests a complex interplay between different Rho GTPases during phagocytosis of
      pathogens.

PMID- 11580755
TI  - NF-kappaB and the MAP kinases/AP-1 pathways are both involved in interleukin-6
      and interleukin-8 expression in fibroblast-like synoviocytes stimulated by
      protein I/II, a modulin from oral streptococci.
AB  - As in rheumatoid arthritis (RA), it was demonstrated recently that bacterial
      fragments of DNA or rRNA are present in the joint and therefore could play a role
      in inducing or perpetuating the disease, this work was initiated to define
      mechanisms that account for the stimulatory activities of the oral streptococcal
      modulin, protein I/II, on fibroblast-like synoviocytes (FLSs) from RA patients.
      FLSs from RA patients were stimulated with protein I/II, and expression of
      interleukin (IL)-6 and IL-8 mRNA was evaluated by reverse transcription
      polymerase chain reaction (RT-PCR). Immunoblotting by antibodies specific for
      activated forms of MAPKs and electrophoretic mobility shift assays (EMSAs) were
      performed to study downstream signalling, which allowed the synthesis of IL-6 and
      IL-8. We reported that protein I/II interactions with FLSs from RA patients
      trigger the synthesis and release of IL-6 and IL-8. We also demonstrated that
      protein I/II enhances the phosphorylation of ERK 1/2, p38 and JNKs and that ERK
      1/2 and JNK MAPKs seem to play a more important role than p38 in protein I/II
      mediated synthesis of IL-6 and IL-8. Our experiments also indicated that
      stimulation of FLSs with protein I/II induces nuclear translocation of NF-kappaB,
      AP-1-binding activity and that NF-kappaB plays a major role in IL-6 and IL-8
      secretion from activated cells.

PMID- 11580757
TI  - Cortical dysplasia: electroclinical, imaging, and neuropathologic study of 13
      patients.
AB  - PURPOSE: The aim of this study was to correlate the electroclinical and
      radiologic data with the neuropathologic findings and surgical outcome in
      epileptic patients with epilepsy and Taylor's focal cortical dysplasia (TFCD) and
      to characterize further the abnormal intermediate filaments expression in the
      balloon cell present in the peculiar dysplasia. METHODS: We retrospectively
      selected 13 TFCD patients who underwent surgery for intractable epilepsy with the
      aim of removing the magnetic resonance (MR)-detectable lesion and/or the
      epileptogenic zone defined by stereoelectroencephalographic recordings. The
      surgical specimens were analyzed by means of routine neuropathologic and
      immunocytochemical studies. Antisera against different intermediate filaments
      also were used in serial adjacent sections to evaluate their coexpression in
      balloon cells. RESULTS: Histopathologic abnormalities typical of TFCD were found
      not only within the MR-visible lesions but also in most of the epileptogenic
      zones with no MR signal alterations. Furthermore, the MR-visible lesions
      contained a high proportion of cells with an abnormal expression of intermediate
      filament proteins. After a long follow-up, 10 of the patients are now seizure
      free. CONCLUSIONS: Our findings indicate that highly epileptogenic zones may
      correspond to tissue alterations not revealed by neuroimaging. Furthermore, the
      immunocytochemical data show that the dysplastic tissue detected by MR contained
      high concentrations of cells filled with abnormal intermediate filaments. The
      detected colocalization of neuronal and glial markers in balloon cells indicates
      a failure of cellular commitment during development.

PMID- 11580756
TI  - Loss of the potassium channel beta-subunit gene, KCNAB2, is associated with
      epilepsy in patients with 1p36 deletion syndrome.
AB  - PURPOSE: Clinical features associated with chromosome 1p36 deletion include
      characteristic craniofacial abnormalities, mental retardation, and epilepsy. The
      presence and severity of specific phenotypic features are likely to be correlated
      with loss of a distinct complement of genes in each patient. We hypothesize that
      hemizygous deletion of one, or a few, critical gene(s) controlling neuronal
      excitability is associated with the epilepsy phenotype. Because ion channels are
      important determinants of seizure susceptibility and the voltage-gated K(+)
      channel beta-subunit gene, KCNAB2, has been localized to 1p36, we propose that
      deletion of this gene may be associated with the epilepsy phenotype. METHODS:
      Twenty-four patients were evaluated by fluorescence in situ hybridization with a
      probe containing KCNAB2. Clinical details were obtained by neurologic examination
      and EEG. RESULTS: Nine patients are deleted for the KCNAB2 locus, and eight (89%)
      of these have epilepsy or epileptiform activity on EEG. The majority of patients
      have a severe seizure phenotype, including infantile spasms. In contrast, of
      those not deleted for KCNAB2, only 27% have chronic seizures, and none had
      infantile spasms. CONCLUSIONS: Lack of the beta subunit would be predicted to
      reduce K(+) channel-mediated membrane repolarization and increase neuronal
      excitability, suggesting a possible relation between loss of this gene and the
      development of seizures. Because some patients with seizures were not deleted for
      KCNAB2, there may be additional genes within 1p36 that contribute to epilepsy in
      this syndrome. Hemizygosity of this gene in a majority of monosomy 1p36 syndrome
      patients with epilepsy suggests that haploinsufficiency for KCNAB2 is a
      significant risk factor for epilepsy.

PMID- 11580758
TI  - Surgical resection for intractable epilepsy in "double cortex" syndrome yields
      inadequate results.
AB  - PURPOSE: To analyze the results of surgical treatment of intractable epilepsy in
      patients with subcortical band heterotopia, or double cortex syndrome, a diffuse
      neuronal migration disorder. METHODS: We studied eight patients (five women) with
      double cortex syndrome and intractable epilepsy. All had a comprehensive
      presurgical evaluation including prolonged video-EEG recordings and magnetic
      resonance imaging (MRI). RESULTS: All patients had partial seizures, with
      secondary generalization in six of them. Neurologic examination was normal in
      all. Three were of normal intelligence, and five were mildly retarded. Six
      patients underwent invasive EEG recordings, three of them with subdural grids and
      three with stereotactic implanted depth electrodes (SEEG). Although EEG
      recordings showed multilobar epileptic abnormalities in most patients, regional
      or focal seizure onset was recorded in all. MRI showed bilateral subcortical band
      heterotopia, asymmetric in thickness in three. An additional area of cortical
      thickening in the left frontal lobe was found in one patient. Surgical procedures
      included multiple subpial transections in two patients, frontal lesionectomy in
      one, temporal lobectomy with amygdalohippocampectomy in five, and an additional
      anterior callosotomy in one. Five patients had no significant improvement, two
      had some improvement, and one was greatly improved. CONCLUSION: Our results do
      not support focal surgical removal of epileptogenic tissue in patients with
      double cortex syndrome, even in the presence of a relatively localized
      epileptogenic area.

PMID- 11580759
TI  - Late seizure recurrence after multiple subpial transections.
AB  - We studied long-term outcome (range, 28-89 months; mean, 56 months) after
      multiple subpial transections (MST) for medically refractory epilepsy. Forty
      three (79.6%) of 54 patients had a consistent significant reduction in seizure
      frequency, and 27 (50%) of the 54 were either entirely seizure free or virtually
      so. However, 10 (18.5%) patients sustained an increase in seizure frequency
      several years after surgery, after showing initial postoperative improvement.
      This suggests that late seizure recurrence is a more important problem in cases
      in which MST has been performed than for pure resections.

PMID- 11580760
TI  - Postmarketing experience with topiramate and cognition.
AB  - Ideal antiepileptic drugs (AEDs) are designed to stop seizures with limited
      central nervous system (CNS) side effects. However, CNS-related treatment
      emergent adverse events (TEAEs) often occur in patients receiving AEDs.
      Topiramate (TPM) is an AED proven to be safe and effective as adjunctive
      treatment for epilepsy patients with partial seizures. Double-blind, placebo
      controlled, multicenter trials demonstrated potential effects on cognition. The
      P.A.D.S. (post-marketing antiepileptic drug survey) group, a cooperative group of
      14 epilepsy centers that collaborate on obtaining data about new AEDs and
      devices, prospectively collected standardized data forms before and during
      treatment with TPM for epilepsy, and analyzed the postmarketing experience of CNS
      TEAEs with TPM. Our results from 701 treated patients show that cognitive
      complaints were the most common reason to discontinue TPM. The presence of
      complaints did have predictive value if the patient would discontinue TPM,
      although was not specific as to when discontinuation would occur. The spectrum of
      complaints in our open-label prospective multicenter postmarketing study was
      similar to those observed in controlled clinical trials. We were unable to
      demonstrate a specific population, dose titration, or concomitant AED that was at
      risk to discontinue treatment. We conclude that most patients treated with TPM
      will continue therapy beyond 6 months. Cognitive complaints and not efficacy
      reflect the primary reason for discontinuing therapy. Psychomotor slowing was the
      most common complaint, yet most patients elect to continue treatment, with
      "better" or "much better" ratings of both seizure and global improvement during
      treatment.

PMID- 11580761
TI  - Long-term valproate and lamotrigine treatment may be a marker for reduced growth
      and bone mass in children with epilepsy.
AB  - PURPOSE: To determine whether long-term treatment with valproate (VPA) and/or
      lamotrigine (LTG) in children with epilepsy is associated with altered growth
      and/or bone metabolism. METHODS: Twenty-seven boys and 26 girls, aged 3 to 17
      years (9.2 +/- 3.9, mean +/- SD), with epilepsy treated with VPA and/or LTG for >
      or =2 years were evaluated for growth, nutrient intakes, physical activity, bone
      mineral density (BMD), and blood biochemical indices of mineral and bone
      metabolism. RESULTS: Twenty-three (43.4%) of the children had a body height below
      the 10th percentile. Z-scores for BMD below -1.5 occurred in 24.4% of the
      children. When patients were divided into two groups according to daily activity
      score, a significantly lower Z-score for total body BMD (p = 0.007), percentile
      for body height (p = 0.05), and plasma parathyroid hormone (PTH; p = 0.04),
      osteocalcin (p = 0.04) and 25-hydroxyvitamin D (25OHD) (p = 0.01) were found in
      the inactive compared with the active group. Z-score for total body BMD was
      correlated with daily activity score (r = 0.43, p = 0.008). Plasma intact
      osteocalcin and intact PTH values correlated significantly (r = 0.36, p = 0.02).
      Plasma 1,25-dihydroxyvitamin D was within normal range for all subjects. When
      patients were divided into LTG-alone, VPA-alone, and LTG-plus-VPA treatment
      groups, significantly lower (p < 0.05) plasma osteocalcin and percentile for body
      height were found in the VPA-plus-LTG treatment group. CONCLUSIONS: Long-term VPA
      and LTG therapy, particularly when combined, is associated with short stature,
      low BMD, and reduced bone formation. These alterations may be mediated primarily
      through reduced physical activity rather than through a direct link to the VPA
      and/or LTG therapy.

PMID- 11580762
TI  - Vagus nerve stimulation in children with refractory seizures associated with
      Lennox-Gastaut syndrome.
AB  - PURPOSE: Vagus nerve stimulation (VNS) is approved for use for refractory partial
      seizures. Nevertheless, information regarding VNS therapy for special
      populations, including Lennox-Gastaut syndrome (LGS) is limited. We discuss the
      effectiveness, tolerability, and safety of VNS therapy in patients with LGS.
      METHODS: A six-center, retrospective study evaluated the effectiveness of VNS
      therapy in patients with LGS at 3 and 6 months and compared preimplant and
      postimplant seizure frequency. Adverse effects and quality of life (QOL) were
      included as secondary measures. RESULTS: Fifty patients, median age 13 years,
      with medically refractory epilepsy, were implanted. Median age at onset of
      seizures was 1.4 years, and a median of nine anticonvulsants (AEDs) had been
      tried before implantation. Data-collection forms were designed for
      retrospectively gathering data on each patient's preimplant history, seizures,
      implants, device settings, QOL, and adverse events. Median reductions in total
      seizures were 42% at 1 month, 58.2% at 3 months, and 57.9% at 6 months. The most
      common adverse events reported were voice alteration and coughing during
      stimulation. Other uncommon adverse events included increased drooling and
      behavioral changes. Investigators noted that QOL had improved for some patients
      in the study. CONCLUSIONS: VNS is an effective treatment for medically refractory
      epilepsy in LGS. This treatment is well tolerated, safe, and may improve QOL.

PMID- 11580763
TI  - Silent celiac disease in patients with childhood localization-related epilepsies.
AB  - PURPOSE: To evaluate how many patients with a clinical picture of idiopathic
      childhood localization-related epilepsies may also have silent celiac disease
      (CD). This will help determine whether investigation for CD should be restricted
      to those patients with childhood partial epilepsy with occipital paroxysms (CPEO)
      or should be extended to all patients with childhood partial epilepsy (CPE)
      regardless of seizure type and electroencephalographic (EEG) paroxysms. METHODS:
      The study group consisted of 72 patients (31 girls and 41 boys; mean age, 12.6 +/
      4.28 years; age at onset, 6.4 +/- 3.7 years) who were observed consecutively
      over a 5-year period and who received an initial diagnosis of idiopathic CPE. A
      diagnosis of CD was confirmed by using enzyme-linked immunosorbent assay (ELISA)
      to assess the presence of antigliadin antibodies and the immunofluorescent
      undirected test to assess the presence of antiendomysium antibodies. RESULTS:
      Twenty-five patients had CPEO, whereas the remaining 47 had CPE with
      centrotemporal spikes (CPEC). None of the patients with CPEC had positive
      antibody tests. Of the 25 patients with CPEO, two (8%) had antiendomysium
      immunoglobulin (Ig) A antibodies. In both of these patients, the jejunal biopsy
      showed atrophy of the villi and hyperplasia of the crypts, consistent with a
      diagnosis of CD. Brain computed tomography (CT) was normal in one of these
      patients and revealed occipital corticosubcortical calcifications in the other.
      CONCLUSIONS: Our study indicates that CD screening should be performed routinely
      only in patients with CPEO.

PMID- 11580764
TI  - A prospective study of the incidence of the purple glove syndrome.
AB  - PURPOSE: Phenytoin (PHT) has been widely used intravenously for the treatment of
      seizures since 1956, and for many years, it has been considered first-line
      therapy for status epilepticus. It is routinely administered intravenously in
      emergency departments and hospitals for patients who have had isolated seizures
      and for many patients undergoing neurosurgical procedures who are unable to
      receive oral medication. Adverse reactions from PHT have been widely studied for
      years, but in the past decade, new adverse reactions have been identified. One of
      these adverse reactions is the purple glove syndrome (PGS), characterized by
      edema, discoloration, and pain distal to the site of i.v. administration of PHT.
      Because there have been no prospective reports of the incidence of PGS, the
      objective of the study was to report the incidence of this syndrome. METHODS: We
      enrolled 179 consecutive exposures to i.v. PHT at Henry Ford Hospital. Distal
      portions of the upper extremities were examined and digitally photographed by one
      of the authors (J.G.B.). The photos were blindly evaluated by the third author
      (G.L.B.) for PGS. Demographic and pertinent medical history was recorded for all
      patients, and outcome for those who experienced PGS was recorded. Associations
      between PGS, demographic, and medical history information were assessed. RESULTS:
      In only three of the 179 exposures did PGS develop. In both patients, the
      severity of the clinical picture was mild and did not required prolonged
      hospitalization or specialized treatment. CONCLUSIONS: PGS is an infrequent and
      mild adverse effect of i.v. PHT administration.

PMID- 11580765
TI  - Social functioning, psychological functioning, and quality of life in epilepsy.
AB  - PURPOSE: Part of our research intended to explain "Quality of Life" (QoL)
      differences between people with epilepsy. To this end, a series of already
      existing generic and disease-specific health status measures were used. In this
      study, they were considered as determinants of people's QoL, whereas QoL itself
      was conceived as a general "value judgment" about one's life. METHODS: From the
      records of four outpatient clinics, 210 persons with epilepsy were randomly
      selected. During their visit to the outpatient clinic, they completed a
      questionnaire assessing, among other things, health perceptions and social and
      psychological functioning. Additional information about their medical and
      psychosocial status was gathered from the patient files. Data were analysed by
      using a hierarchical regression analysis. RESULTS: In decreasing order of
      importance, "psychological distress," "loneliness," "adjustment and coping," and
      "stigma perception" appeared to contribute most significantly to the outcome QoL
      as judged by the patients themselves, regardless of their physical status. In the
      final model, none of the clinical variables (onset, seizure frequency, side
      effects of antiepileptic drugs) contributed significantly anymore to the
      patients' "quality-of-life judgement." Apparently the effect of other variables
      such as seizure frequency and health perceptions, medication and side effects,
      life fulfillment, self-esteem, and mastery is mediated by these variables.
      CONCLUSIONS: Because all of the variance in QoL of the patients was explained by
      the psychosocial variables included in this study, health professionals should be
      aware of the significance of the psychosocial functioning of the patients and the
      role it plays in the achievement of a good QoL. Both informal and professional
      support may be an adjunct to conventional treatment. In future research, this
      issue should be given high priority.

PMID- 11580766
TI  - Psychosocial adjustment of people with epilepsy in Hong Kong.
AB  - PURPOSE: In light of the issues associated with the psychosocial adjustment of
      people with epilepsy that have been widely reported, this study examined these
      issues within a Chinese cultural context. METHODS: Fifty patients with epilepsy
      completed The Washington Psychosocial Inventory, the Coping Inventory for
      Stressful Situations, and a questionnaire that assessed their psychosocial
      difficulties and coping styles. Multiple regression procedure was used to examine
      the strength of various medical and social factors in predicting the psychosocial
      adjustment problems of these participants. RESULTS: Social factors, such as self
      perception and coping strategies, were more powerful predictors of psychosocial
      adjustment in people with epilepsy than the medical factors associated with
      epilepsy. CONCLUSIONS: These findings showed that psychosocial maladjustment is a
      significant issue for people with epilepsy in Hong Kong. The emerging importance
      of social factors as predictors of psychosocial adjustment in epilepsy, as
      compared with medical factors, highlights the need for developing tailored
      counseling therapy and social support groups for people with epilepsy.

PMID- 11580767
TI  - Seizure-associated headache in epilepsy.
AB  - PURPOSE: Headache is often ignored as a symptom of epileptic seizures. The
      purpose of this prospective study was to analyze frequency, classification, and
      characteristics of seizure-associated headache (SH) according to the criteria of
      the International Headache Society. METHODS: Over a period of 15 months, 341
      patients with epilepsy, consecutively evaluated at our outpatient clinic for SH,
      completed a standardized questionnaire. RESULTS: Of the 341 epilepsy patients,
      115 (34%) experienced SH with a pain intensity of 6.1 +/- 1.6 (SD) on the visual
      analogue scale and a duration of 12.8 +/- 15.7 (SD) h. Seizures were always
      accompanied by headache in 69 (60%) of these 115 patients. SH occurred in four
      (3%) of 115 patients only preictally, in 31 (27%) of 115 patients periictally,
      and in 80 (70%) of 115 patients only postictally. In the majority of the 115
      patients (55.7%), SH could be classified as migraine headache, whereas in 36.5%,
      as tension-type headache. The type of SH was not correlated with sex, an epilepsy
      syndrome, or a seizure type. Migraine-like SH was significantly associated with a
      history of migraine (p < 0.001). In 20 (77%) of the 26 patients experiencing
      migraine-like SH with a history of migraine, the phenomenology of migraine-like
      SH and migraine attacks was identical. CONCLUSIONS: SH is a frequent, long
      lasting, and severe symptom of epileptic seizures, causing major impairment of
      daily living. A history of migraine significantly increases the risk for
      developing migraine-like SH.

PMID- 11580768
TI  - Hot water epilepsy: clinical and electrophysiologic findings based on 21 cases.
AB  - PURPOSE: Our aim is to outline the clinical and electroencephalographic (EEG)
      features of patients with hot water epilepsy (HWE), a rare and unique form of
      reflex epilepsy. METHODS: Twenty-one patients with HWE, seen in our clinic until
      1999, were studied. Male outnumbered female subjects in a ratio of 3:1. The age
      at the onset of seizures ranged from 19 months to 27 years (mean age at onset, 12
      years). RESULTS: The main factors precipitating seizures were bathing with hot
      water and/or pouring water over the head. Six patients reported self-induction,
      either by increasing the heat or the amount of water and/or recalling earlier
      bathing experiences. Nine patients expressed feeling pleasure during the
      seizures. Twenty patients had partial seizures, eight of whom also had
      secondarily generalized seizures. One patient had apparent generalized seizures
      only. Spontaneous seizures were present in 62% of the cases. Interictal
      epileptogenic abnormalities were documented in the EEGs of eight patients; the
      other eight had normal EEGs. The major sites of epileptogenic activity were over
      the unilateral temporal regions (in 40% of patients). Neuroimaging studies
      available for 12 patients (four cranial computed tomography and eight cranial
      magnetic resonance imaging scans) revealed normal findings. Seizure control in
      patients who were followed up was achieved by reducing the temperature or the
      duration of the bath or shower; several of the patients required medication.
      CONCLUSIONS: The major findings of this study are that HWE has a male
      preponderance, can be self-induced, is often done for pleasure, has complex
      triggering factors, and shows temporally located abnormalities in the EEGs.
      Although HWE is generally known to be self-limited, antiepileptic drug treatment
      may sometimes be necessary to control seizures. Hot water epilepsy should be
      classified separately among the epileptic syndromes.

PMID- 11580769
TI  - Study on photo-pattern sensitivity in patients with electronic screen game
      induced seizures (ESGS): effects of spatial resolution, brightness, and pattern
      movement.
AB  - PURPOSE: With the ever-increasing popularity of computers, electronic screen game
      induced seizure (ESGS) is beginning to pose a serious social problem. To
      elucidate the pathophysiology of ESGS, with the ultimate goal of prevention, we
      have been studying photo-pattern sensitivity in detail with a pattern-stimulation
      test using a CRT (cathode ray tube) display. This method is referred to as the
      "CRT-pattern test." METHODS: We studied 17 patients brought to our department for
      evaluation of ESGS. EEG responses were recorded during exposure to various
      patterns consisting of three elements: spatial resolution, brightness perception,
      and pattern-movement recognition displayed on a CRT monitor. Photo-paroxysmal
      response (PPR) frequencies were compiled for each stimulation. RESULTS: PPR was
      induced by the CRT-pattern test in nine of the 17 cases. In four cases, PPR
      induction was obtained only after introducing CRT-pattern tests in addition to
      standard intermittent photic stimulation (IPS). The rate of PPR induction
      differed according to the type of pattern, spatial frequency, and pattern
      reversal frequency. However, neither the clarity of the edges of a pattern nor
      changes in the brightness of a pattern element had any effect on the rate of PPR
      induction. With the exception of a few subjects, the stimulation caused by
      pattern movement was not effective in eliciting PPR. Six cases in whom spatial
      resolution was involved showed occipital dominance in PPR provocation, and three
      in whom brightness perception and pattern movement recognition was involved
      showed frontal dominance. CONCLUSIONS: The CRT-pattern test is useful for
      identifying patients with photosensitivity among patients considered to have
      incidental or nonphotosensitive seizures unresponsive to standard IPS. Patients
      with ESGS caused by photosensitivity can be divided into two groups: those with
      occipital dominance for PPR provocation, in whom spatial resolution is involved;
      and another group with frontal dominance, in whom brightness perception and
      pattern-movement recognition (or possibly perception of colors) are involved.

PMID- 11580770
TI  - Neuropathological findings in a patient with epilepsy and the Parry-Romberg
      syndrome.
AB  - PURPOSE: The Parry-Romberg syndrome is an unusual disorder frequently associated
      with epilepsy. The origin of this disease, and the cause of epilepsy, are
      unknown. This study is the first reported case of the Parry-Romberg syndrome,
      with intractable temporal lobe epilepsy, in which detailed microanatomic analyses
      have been performed on resected brain tissue obtained after surgical
      intervention. METHODS: Standard histopathologic methods and correlative light and
      electron microscopy, combined with immunocytochemical techniques, were used to
      study in detail the synaptic microorganization of the resected hippocampal
      formation. RESULTS: After surgery, the patient was seizure free (follow-up period
      of 4 years and 7 months). The resected temporal lobe showed a variety of dramatic
      microanatomic alterations (small groups of ectopic cells, neuronal loss, gliosis,
      and activated microglial cells) in mesial structures, including the entorhinal
      cortex, subiculum, and dentate gyrus. At the electron-microscopic level, we found
      that in the dentate gyrus, the number of synapses in the cell-sparse region
      adjacent to the ectopic mass of neurons was almost twice that found in the
      molecular and polymorph cell layers, indicating the intrusion of neuritic
      processes and synapse formation. In addition, the symmetrical axosomatic synapses
      characteristically found on granule cells, which are likely derived from gamma
      aminobutyric acid (GABA)ergic inhibitory basket cells, were not observed.
      CONCLUSION: The complete seizure relief after surgery suggests that the pacemaker
      region(s) of seizure activity were within the resected tissue. However, we do not
      know which of the multiple neuropathologic findings reported here were the
      primary cause of seizure activity. Nevertheless, the changes found in the dentate
      gyrus circuitry appear to be among the most important alterations that would lead
      to epilepsy.

PMID- 11580771
TI  - Hemifacial seizure of cerebellar ganglioglioma origin: seizure control by tumor
      resection.
AB  - The cerebellum is known to have an inhibitory effect on seizures. Nevertheless,
      cerebellar dysplastic lesions can be epileptogenic. A 4-month-old infant had
      paroxysmal facial contractions; tachypnea and nystagmoid eyeball and tremulous
      movements were occasionally combined. These evolved to stereotypic clinical
      patterns and frequencies, which increased despite administration of antiepileptic
      drugs (AEDs). Magnetic resonance imaging (MRI) demonstrated a mass arising from
      the superior cerebellar peduncle, although video-scalp EEG monitoring revealed no
      abnormal findings. Positron emission tomography with [(18)F]fluorodeoxyglucose
      revealed focal hypermetabolism in the same area identified by MRI. A depth
      electrode implanted in the mass revealed focal spike-and-wave discharges. The
      lesion was partly removed; pathologic diagnosis was ganglioglioma. Because of
      incomplete seizure control and residual tumor visible on MRI, a second operation
      was performed. After complete excision of the tumor, the patient became seizure
      free without AEDs. This case confirms the presence of seizure originating from
      the cerebellum and emphasizes the need for the complete removal of an
      epileptogenic lesion.

PMID- 11580772
TI  - Melatonin effect on seizures in children with severe neurologic deficit
      disorders.
AB  - PURPOSE: Recently, melatonin has been associated with antiepileptic activity,
      most probably because of its antioxidant activity as a free radical scavenger.
      This study aimed to expand the clinical experience with melatonin as an
      antiepileptic drug (AED) in humans. METHODS: Six children (aged 2-15 years), with
      severe intractable seizures, were treated with 3 mg of oral melatonin 30 min
      before bedtime, in addition to their previous AED treatment for 3 months. A diary
      of clinical seizure activity (time of day, duration, and type) was kept by
      parents for a month before and during treatment. Five patients underwent a
      baseline polysomnography, and three also were monitored during melatonin
      treatment. RESULTS: With the exception of the parents of one child, all reported
      a significant clinical improvement in seizure activity during treatment,
      particularly during the night. Sleep studies showed a decrease in epileptic
      activity in two of the three patients who were monitored during treatment, and a
      change of sleep efficiency from 84.2% to 89.7% (NS). Improvement in daytime
      behavior and in communication abilities was reported by parents, although it was
      not objectively measured. CONCLUSIONS: This clinical observation adds to the
      growing data showing the antiepileptic effect of melatonin. However, owing to the
      paucity of well-controlled studies, using melatonin as an AED should be limited
      to this specific group of patients with intractable seizures.

PMID- 11580774
TI  - Glossary of descriptive terminology for ictal semiology: report of the ILAE task
      force on classification and terminology.

PMID- 11580775
TI  - Why do anaesthesia journals publish editorials?

PMID- 11580776
TI  - Colour Doppler imaging of the interspinous and epidural space.
AB  - BACKGROUND AND OBJECTIVE: In recent studies, ultrasonic diagnostic imaging has
      proved useful in the screening of the trajectory of the epidural needle. With
      regard to possible side-effects of spinal and epidural anaesthesia caused by
      vessel injury, we aimed to evaluate the usability of Colour Doppler imaging for
      the depiction of interspinous vessels in prepuncture examination. METHODS:
      Ultrasonic examination of the L3/4 interspace area was performed in 20
      volunteers. Using a 4-MHz and a 7-MHz probe with B-mode and Colour Doppler
      imaging, respectively, we compared four settings for the quality of vessel
      depiction in the puncture area. Overall resolution was evaluated according to the
      distinction of landmarks. Vascular structures were identified by pulsation (B
      mode) or blood flow (Doppler). RESULTS: Colour Doppler imaging of the L3/4
      interspace was unachievable using the 7-MHz transducer. Vessel detection was
      possible in 50% of the B-mode images and in all of the 4-MHz Doppler images.
      Vessels were perceptible from a diameter of 0.5 mm. Veins were the predominantly
      visible structures. Overall vessel visibility was best using 4-MHz Colour
      Doppler. CONCLUSIONS: Prepuncture Doppler imaging can provide the epiduralist
      with information regarding the position of vessels in the needle trajectory. This
      might help to reduce complications in regional anaesthesia.

PMID- 11580777
TI  - Reference values for left ventricular function in subjects under general
      anaesthesia and controlled ventilation assessed by two-dimensional
      transoesophageal echocardiography.
AB  - BACKGROUND AND OBJECTIVE: Transoesophageal echocardiography is increasingly used
      for evaluation and monitoring of left ventricular function in anaesthetized
      patients. However, the only available reference values for transoesophageal
      echocardiography were derived from studies in awake subjects. METHODS: We
      determined left ventricular dimensions and systolic function in 45 patients
      without clinical evidence of heart disease who voluntarily underwent
      transesophageal echocardiography under conditions of balanced general
      anaesthesia, controlled fluid administration, supine position, muscle relaxation
      and controlled ventilation. RESULTS: The left ventricular dimensions obtained
      during these conditions were lower than the published normal values in awake
      subjects. The indices of global left ventricular function, however, were similar
      to the normal values obtained by either awake transesophageal echocardiography or
      transthoracic echocardiography. CONCLUSION: We propose using the values obtained
      in our study as reference values for evaluation of left ventricular function in
      patients under general anaesthesia and controlled ventilation.

PMID- 11580778
TI  - Magnesium as part of balanced general anaesthesia with propofol, remifentanil and
      mivacurium: a double-blind, randomized prospective study in 50 patients.
AB  - BACKGROUND AND OBJECTIVE: To test the hypothesis that magnesium sulphate reduces
      the amount of remifentanil needed for general anaesthesia in combination with
      propofol and mivacurium, we studied 50 patients undergoing elective pars plana
      vitrectomy in a double-blind, randomized prospective fashion. METHODS: Magnesium
      sulphate (50 mg kg(-1) body weight) or placebo (equal volume of NaCl) was given
      slowly intravenously after induction of anaesthesia with propofol 1-2 mg kg(-1).
      Anaesthesia was maintained with propofol (using electroencephalographic control),
      mivacurium (according to train-of-four monitoring of neuromuscular blockade) and
      remifentanil (according to heart rate and arterial pressure). RESULTS: We
      observed a significant reduction in remifentanil consumption from 0.14 to 0.09
      microg kg(-1) min(-1) (P < 0.01). Mivacurium consumption was also markedly
      reduced from 0.01 to 0.008 mg kg(-1) min(-1) (P < 0.01), whereas propofol
      consumption remained unchanged. There was a trend towards lower postoperative
      pain scores, less pain medication requirements in 24 h after surgery and less
      postoperative nausea and vomiting in the magnesium group but not statistically
      significant. No side-effects were observed. CONCLUSION: We can recommend the use
      of magnesium sulphate as a safe and cost-effective supplement to a general
      anaesthetic regimen with propofol, remifentanil and mivacurium, although we
      cannot clearly distinguish between a mechanism as a (co)analgesic agent at the
      NMDA-receptor site or its properties as a sympatholytic. The effect of a single
      bolus dose of 50 mg kg(-1) on induction lasts for about 2 h. For longer cases,
      either a continuous infusion or repeated bolus doses might be necessary.

PMID- 11580779
TI  - Anaesthetic management of the airway in The Netherlands: a postal survey.
AB  - BACKGROUND AND OBJECTIVE: A postal survey was conducted in order to investigate
      current practice in airway management amongst Dutch anaesthetists and to
      investigate the role of recent training and the role of an 'Access to the Airway'
      airway management course. METHODS: A questionnaire containing 27 questions was
      sent to all practising anaesthetists in The Netherlands. Questionnaires were
      returned anonymously and were analysed using the Pearson chi(2)-test (P < 0.05)
      with the SPSSR version 8.0 statistical software program. RESULTS: The response
      rate was 42%. Of the respondents, 78% claim often or always to assess the
      expected degree of difficulty in tracheal intubation as part of routine
      preoperative assessment. The American Society of Anesthesiologist's Difficult
      Airway Algorithm was used by 19% of respondents. A wide variety of airway
      management techniques is being used. In 36% of all general anaesthetics a
      laryngeal mask airway is used. In 1.1% of all general anaesthetics tracheal
      intubation is performed with the flexible fibrescope. CONCLUSIONS: Dutch
      anaesthetists, who commenced anaesthetic training after 1988, and those who
      attended the airway management course 'Access to the Airway' are significantly
      more likely to follow the American Society of Anesthesiologist's Difficult Airway
      Algorithm and to use adjunctive techniques for airway management.

PMID- 11580780
TI  - Use of the intubating laryngeal mask in children: an evaluation using video
      endoscopic monitoring.
AB  - BACKGROUND AND OBJECTIVE: The intubating laryngeal mask is designed to act as a
      ventilatory device and as an aid to blind tracheal intubation in adults. The aim
      of this study was to evaluate the efficacy of the intubating laryngeal mask for
      ventilation of the lungs and tracheal intubation in children using video
      endoscopic control. METHODS: The handling and efficacy of the size 3 intubating
      laryngeal mask for tracheal intubation in 80 children weighing > or = 25 kg were
      assessed under video-endoscopic control. Ease of intubating laryngeal mask
      insertion, adequacy of lung ventilation through the intubating laryngeal mask and
      airway sealing pressures were recorded. Tracheal intubation was performed blindly
      by the intubator, while the supervisor observed the procedure on the video
      display. If blind intubation failed at the first attempt, the monitor view was
      used to guide the tracheal tube into the trachea. The success rate and time
      required for successfully placing the tracheal tube were recorded. RESULTS:
      Insertion of the intubating laryngeal mask was easy in all children. Lung
      ventilation through the intubating laryngeal mask was uniformly excellent. Blind
      tracheal intubation at the first attempt was successful in 53 children (66%)
      within 18.8 +/- 4.1 s. Twenty-four of the 27 failed blind intubation attempts
      were successfully intubated with video-endoscopic guidance within 28.6 +/- 9.4 s.
      Two children required replacing the intubating laryngeal mask, one child had to
      be intubated conventionally. CONCLUSIONS: The size 3 intubating laryngeal mask
      provides an airway that is easy to establish in children > or = 25 kg with
      excellent ventilation conditions and allows blind tracheal intubation at the
      first attempt with a high success rate. Endoscopic monitoring improves its safety
      and intubation success rate.

PMID- 11580781
TI  - Anaesthesia for children with epidermolysis bullosa: a review of 20 years'
      experience.
AB  - BACKGROUND AND OBJECTIVE: Epidermolysis bullosa is a rare, genetically determined
      disorder characterized by excessive susceptibility of the skin and mucosa to
      separate from the underlying tissues after mechanical trauma. Patients suffering
      from this disease may have multiple medical problems, but the risk of anaesthesia
      is attributed mainly to oropharyngeal involvement; airway management may be
      hazardous and preservation of mucosa and skin integrity problematical. There is a
      paucity of data in the literature concerning the perioperative management of
      children with epidermolysis bullosa. We present our experience of managing 54
      general anaesthetics (and two local anaesthetics) over the past 20 years.
      METHODS: The case notes of 16 children with epidermolysis bullosa were reviewed.
      The children underwent surgical procedures under local or general anaesthesia
      over a 20-year period. RESULTS: Fifty-four general and two local anaesthetics
      were administered for 58 procedures in 10 children (mean age 12.6 years).
      Surgical procedures included oesophageal dilatation (24), insertion/revision of
      gastrostomy (16), dental procedures (10), hand surgery (2), skin biopsy (2) and
      others (4). Anaesthesia was induced by inhalation in 73.4% of patients and the
      airway was maintained with an endotracheal tube in 64.8%. Monitoring of
      anaesthesia was performed with pulse oximetry (89%), whereas electrocardiography
      and non-invasive blood pressure monitoring were used in 16.6% of cases each. The
      mean duration of anaesthesia was 64 min. Tracheal intubation was difficult in two
      of the five children who were intubated. Mucocutaneous blistering occurred in
      three children, otherwise there was no attributable morbidity. CONCLUSION: With
      maximal skin and mucous membrane protection, anaesthesia in children with
      epidermolysis bullosa may be undertaken with few sequelae.

PMID- 11580782
TI  - Quality of anaesthesia for insertion of tension-free vaginal tape using local
      analgesia and sedation.
AB  - BACKGROUND AND OBJECTIVE: The use of tension-free tape in the vagina is a
      relatively new surgical procedure for the treatment of urinary incontinence.
      Traditionally, the procedure is carried out using local anaesthesia and sedation.
      We aimed to assess the quality of anaesthesia obtained during insertion of
      tension-free vaginal tape using local anaesthetic infiltration and intravenous
      conscious sedation. METHODS: Twenty-four patients were studied using intravenous
      midazolam, fentanyl and infiltration with 0.5% prilocaine and epinephrine. Visual
      analogue scores before operation were used to assess anxiety. The digit symbol
      substitution test was used before and after surgery to assess psychomotor
      recovery, and amnesia for the procedure was assessed by means of picture recall.
      A nurse, anaesthetist and surgeon independently assessed quality of anaesthesia
      based on vocalization, facial expression, movement and co-operation with
      incontinence testing. RESULTS: The nurse, anaesthetist and surgeon reported good
      or excellent conditions in 18, 14 and 22 cases, respectively. There was no
      significant psychomotor impairment using the digit symbol substitution test, with
      mean (standard deviation) preoperative and postoperative scores of 22 (8) and 21
      (7) correctly matched symbol digit pairs. There was a significant correlation
      between preoperative anxiety and intraoperative fentanyl requirement (r=0.48, P <
      0.05). CONCLUSION: Satisfactory anaesthetic conditions can be achieved for the
      insertion of tension-free vaginal tape using local anaesthesia with sedation.

PMID- 11580783
TI  - Anaesthesia for stent graft repair of thoracic aneurysm and coarctation of the
      aorta.
AB  - We present the anaesthetic management of a patient for stenting of a thoracic
      aortic aneurysm at the site of an aortic coarctation. The specific challenges to
      the anaesthetist for this case are outlined. These include the specific problems
      of placing the graft, the obvious risk of aortic rupture and the unfamiliar
      environment of the separate radiological theatre. The advantages and
      disadvantages to the anaesthetist of the treatment of thoracic aortic aneurysms
      with stents are briefly discussed.

PMID- 11580784
TI  - Hypoxic brain damage after intramuscular self-injection of diclofenac for acute
      back pain.
AB  - We present a case of hypoxic brain damage that occurred after intramuscular
      injection of diclofenac due to a severe anaphylactic reaction. A 38-year-old
      nurse treated herself for acute lower back pain with 100 mg diclofenac
      intramuscularly. Five minutes later, she collapsed and developed coma and
      respiratory arrest. After cardiopulmonary resuscitation she was transferred to
      hospital. On admission she was comatose and received controlled ventilation of
      the lungs. Magnetic resonance imaging and computerized tomography showed signs of
      hypoxic brain injury and the patient died from central cardiopulmonary failure 7
      days later. Intramuscular treatment with non-steroidal anti-inflammatory drugs
      such as diclofenac has rare but potentially severe side-effects. Therefore,
      intramuscular injections are inappropriate and should be replaced with oral or
      rectal treatment, which has similar absorption profiles.

PMID- 11580785
TI  - The anaesthetic management of a case of severe upper airways obstruction due to
      an enlarging subglottic benign polyp.
AB  - The use of a newly developed aid to jet ventilation of the lungs, a modified Ben
      Jet tube (the Hunsaker Monjet tube), is described in a patient with partial upper
      airway obstruction. This report highlights an unusual use of this device. The
      Monjet is a fluoroplastic, monitored, self-centring, fine bore tube that can be
      inserted from the mouth through to the subglottic region. It was originally
      developed to anaesthetize healthy patients without airway obstruction who were
      undergoing suspension microlaryngoscopy.

PMID- 11580786
TI  - Treatment of a case of acute right heart failure by inhalation of iloprost, a
      long-acting prostacyclin analogue.
AB  - Perioperative acute right heart failure after orthotopic heart transplantation
      contributes significantly to morbidity and mortality. Vasodilators administered
      intravenously may decrease pulmonary vascular resistance, but also affect
      systemic circulation. A decrease of mean arterial pressure will result in reduced
      right coronary blood flow and deterioration of right ventricular performance.
      Vasodilators administered by inhalation, i.e. nitric oxide and prostacyclin, are
      attractive due to a more selective effect on the pulmonary circulation. This is
      the first report on the use of aerosolized iloprost, a long-acting prostacyclin
      analogue, applied for treatment of postoperative right heart failure in cardiac
      transplantation. After uneventful surgery, a heart transplant recipient was
      extubated on the first postoperative day and exhibited right heart failure on the
      following day. Standard treatment did not resolve this clinical problem
      sufficiently. A trial with inhalation of iloprost (16 microg per inhalation
      cycle, applied six times per day) was initiated. Iloprost inhalation resulted in
      a sufficient decrease of pulmonary vascular resistance (-23.5%), while cardiac
      index (+24.0%) and mixed venous saturation (+9.0%) increased. No profound effect
      on the systemic vascular resistance was observed (-2.8%). Iloprost inhalation may
      be an effective alternative to nitric oxide in the intensive care management of
      acute right heart failure after orthotopic heart transplantation. Due to the
      prolonged effect on the pulmonary vascular resistance, iloprost is especially
      useful for extubated patients.

PMID- 11580787
TI  - Malignant hyperinflation of the nondependent lung during chest surgery.
AB  - Unilateral malignant hyperinflation of the lungs during positive pressure
      mechanical ventilation was described during aggressive respiratory therapy of
      unilateral lung disease or in situations of significant difference in compliance
      between the two lungs. We report a case of malignant hyperinflation of the
      nondependent lung during chest surgery. The differential diagnosis and treatment
      with differential lung ventilation are described.

PMID- 11580788
TI  - Rapacuronium for neuromuscular blockade in two myasthenic patients undergoing
      trans-sternal thymectomy.

PMID- 11580789
TI  - Pericardial tamponade as a delayed complication of central venous
      catheterization.

PMID- 11580790
TI  - Bibliometrics and a culture of measurement.

PMID- 11580792
TI  - Israeli nurses' knowledge of health care reforms.
AB  - OBJECTIVES: This study examines health care reforms' implementation processes
      from the perspective of nurses' knowledge regarding the reforms. The research has
      been carried out in the Israeli context, where health care reforms were initiated
      in 1995. Three specific research questions were formulated: (a) What is the level
      of nurses' knowledge regarding the recommendations of the Netanyahu committee?
      (b) What is the level of nurses' knowledge concerning the basic principals of the
      National Insurance Law? and (c) Are there knowledge differences relating to
      employment setting (hospital, community, and educational settings), nurses' roles
      (managerial vs. staff nurses), years of experience, and level and type of
      education? METHOD: The stratified nonproportional random sample consisted of a
      total of 468 nurses. Of these nurses, 206 were employed in community settings
      (136 in curative care, and 70 in preventive care), 137 were employed in hospital
      settings, and 125 worked in schools and departments of nursing. Research tools,
      developed for the purpose of this study, included the nurses' knowledge
      questionnaire comprised of five subscales, and the knowledge relevancy
      questionnaire. RESULTS: Overall, data demonstrated a low to moderate level of
      knowledge on all knowledge scales. Knowledge level on the criteria questions was
      particularly low. Contrary to the low level of knowledge, nurses regarded health
      care reforms' knowledge as highly relevant to their work life. Curative setting,
      an extensive work experience, managerial position, and non-nursing academic
      degree were all positively related to higher levels of reforms' knowledge.
      CONCLUSION: These findings should encourage both policy makers and managers in
      various health care organizations to develop programs for informing health care
      providers on central aspects of health care reforms considered most relevant to
      the practice setting.

PMID- 11580793
TI  - An archaeology of caring knowledge.
AB  - BACKGROUND: There have been repeated attempts, especially during the last 20
      years, to say precisely what caring in nursing is. Authors who undertake this
      task usually begin with the observation that the concept of caring is complex and
      elusive, and suggest that their contribution will help to clarify this most
      confused of notions. However, they are always followed by other authors, who do
      exactly the same thing. We seem to be no closer, now, to a clarification of
      caring than we have ever been. AIM: The paper offers a diagnosis of this
      situation, and explains why the project of retrieving caring from its elusiveness
      is an impossible one. I will suggest that this has nothing to do with the concept
      of caring, as such. Rather, the impossibility of the task follows from what these
      authors take to be knowledge of caring. METHOD: I present an analysis of some
      presuppositions about what knowledge is. These presuppositions pervade the
      literature on caring, and can be summarized as follows: knowledge of caring is an
      aggregate of things said about it, derived from a potentially endless series of
      associations, grouped into attributes on the basis of resemblances, and conceived
      as a holistic description of the phenomenon. Further, I suggest that this
      analysis is akin to the one which Foucault offers of sixteenth century knowledge.
      CONCLUSIONS: The analysis suggests that this way of knowing is approximately 350
      years out of date, and explains why the task of arriving at knowledge (in this
      sense) is impossible. Moreover, Foucault's claim that sixteenth century knowledge
      is "plethoric yet absolutely poverty-stricken" applies, with equal force, to
      nursing's knowledge of caring.

PMID- 11580794
TI  - Reflective practice and clinical supervision: meticulous rituals of the
      confessional.
AB  - BACKGROUND: Reflective practice and clinical supervision are progressively
      asserting hegemony upon nursing practice with claims of emancipation and
      empowerment. However, this is being achieved in an environment where there is
      little critical debate about the assumptions on which these practices are based.
      AIM: This paper sets out to challenge the basis upon which reflective practice
      and clinical supervision are promoted within nursing discourse by employing
      Michel Foucault's (1982) concept of governmentality. Theme. A broad Foucauldian
      perspective is used to demonstrate how the technologies of reflective practice
      and clinical supervision have been accommodated within modern forms of
      government. These technologies are consistent with the flattened hierarchies and
      increasing dispersal of practitioners in contemporary health care. In this
      context reflective practice and clinical supervision can be shown to function in
      two independent but interrelated ways. First as modes of surveillance
      disciplining the activity of professionals. Second, as "confessional" practices
      that work to produce particular identities--autonomous and self-regulating.

PMID- 11580795
TI  - John Heron's six-category intervention analysis: towards understanding
      interpersonal relations and progressing the delivery of clinical supervision for
      mental health nursing in the United Kingdom.
AB  - AIMS: This paper provides a critique of how Heron's six-category intervention
      analysis framework has been adopted by nursing in the United Kingdom (UK) as a
      theoretical framework in nursing research and model for clinical supervision.
      From this, its merits as an analytic framework and model for clinical supervision
      in nursing are discussed. BACKGROUND: Heron's six-category intervention analysis
      has been acknowledged as a means by which nursing could develop its therapeutic
      integrity. It has also been used as a theoretical framework in nursing research
      focusing on nurses' perceptions of their interpersonal style. More recently
      descriptions of this framework have been proposed as a structure for clinical
      supervision. However, its use as a theoretical framework to underpin research
      investigating the interpersonal skills of nurses and as a model of clinical
      supervision must firstly be scrutinized. FINDINGS: Returning to Heron's original
      description and comparing this with its current adoption in the UK,
      misconceptions of this framework can be identified. Its value as an analytic tool
      investigating interpersonal relations in nursing has still to be evaluated.
      Furthermore, nursing's emphasis on certain intervention categories has undermined
      the potential potency of this framework and its contribution as a model for
      clinical supervision in nursing. CONCLUSION: We argue that Heron's six-category
      intervention analysis as a framework to investigate the interpersonal competence
      of nurses, particularly mental health nurses, requires investigation. This, in
      turn, would provide an opportunity to challenge the framework's theoretical
      standpoint. In addition to its value as an analytic tool, all six categories of
      Heron's framework have equal relevance to its contribution in nursing as a
      supervision model.

PMID- 11580796
TI  - Models of psychiatric nursing education in developing African countries: a
      comparative study of Botswana and Nigeria.
AB  - BACKGROUND: Against the perspectives of the mental health needs of the people of
      Africa, this study explored and compared the models of psychiatric-mental health
      nursing education (PMHNE) in two sub-Saharan African countries--Botswana and
      Nigeria. METHOD: Examination of the existing PMHNE programmes and responses to a
      self-reporting questionnaire administered to psychiatric nurse educators from
      Botswana and Nigeria provided the sources of data. FINDINGS: Findings from both
      countries revealed that participants used various terms to describe the same
      model for PMHNE programmes in the countries. Botswana adopted a more functional
      generalist basic diploma nursing education approach that encouraged an advanced
      postbasic diploma specialization and practice in community psychiatric-mental
      health nursing. Nigeria's model leaned towards a hospital-based basic
      specialization with no defined role for the generalist nurse within the
      psychiatric-mental health nursing care system. Although community theme occurred
      in both countries' curricula, PMHNE in Botswana appeared to be more geared
      towards the community than in Nigeria. While PMHNE and nursing education
      generally is affiliated to the University with a clear pathway within the formal
      higher education system in Botswana, basic and postbasic nursing programmes are
      mostly run independent of the country's formal higher education system in
      Nigeria. CONCLUSION: A model that streamlined PMHNE within the general system of
      education in both countries was proposed. It was stressed that one key concept
      that must underlie the development of PMHNE in the two countries, and Africa in
      general, was the need to create a psychiatric-mental health nursing education
      programme and role that would be appropriate for people's mental health needs and
      the provision of quality nursing care.

PMID- 11580797
TI  - Midwives' perceptions of the use of technology in assisting childbirth in
      Northern Ireland.
AB  - AIM OF THE PAPER: The aim of this paper is to report a survey of midwives' views
      on the use of technology in assisting births. BACKGROUND: The research was
      designed to provide a deeper understanding of the integration of technology into
      midwives' practice and to identify and examine aspects of training needs.
      METHODS: Over 400 midwives responded to a questionnaire seeking information on
      their experiences and perceived competence with labour ward technology, with a
      particular focus on the use of cardiotocograph machines (CTGs) for electronic
      foetal monitoring. The survey sought views on the extent to which midwives trust
      the technology, their perceived levels of training and competence, their
      awareness of policy relating to technological intervention and the issue of
      women's choice in whether the progress of their delivery is technologically
      monitored. FINDINGS: The majority of midwives in this survey trust the use of
      technology but have concerns about issues of safety in relation to potential
      faults, and to their perceived lack of training in technology usage. The majority
      also indicated that they prefer a nontechnological birth although many point to
      the benefits of technological support when difficulties are encountered. The use
      of technology is seen as multi-professional and there was much support among the
      respondents for multi-disciplinary training in the use of technologies in future
      curricula. CONCLUSIONS: If the various findings of this sample survey were to be
      consolidated for midwives as a whole, they suggest that provisions for continuing
      professional development may need to address technological awareness and
      competence in a more focused manner than is discernible at present.

PMID- 11580798
TI  - The maternity information concerns of Somali women in the United Kingdom.
AB  - AIMS: The aims of the study were to explore the maternity information concerns of
      a group of Somali women in a Northern English city and to investigate the
      relationships of these women with maternity health professionals. BACKGROUND: The
      Somali community is one of the most established ethnic minorities in the United
      Kingdom (UK). The health needs of this group and in particular, the information
      needs of Somali women with respect to pregnancy, childbirth and post-natal care
      are poorly understood. To facilitate information provision to birthing mothers
      and to support maternal decision-making among minority ethnic women, research is
      required to understand and identify their information needs. METHODS: A user
      centred study utilizing a focus group and semi-structured interviews with English
      speaking and non-English speaking Somali women was conducted in a large English
      city. Discussions were audiotaped, translated, transcribed and then analysed
      using a variation of the constant comparative METHOD: Themes and categories were
      identified across transcripts during data collection and analysis and appropriate
      quotations are used to illustrate all themes. FINDINGS: Major findings that
      emerged from the analysis related to contact with health professionals, language
      support and information and satisfaction with health professionals. The findings
      indicate key maternity information concerns of Somali women with regard to
      maternity issues and have a number of implications for midwifery and nursing
      practice. CONCLUSIONS: Poor communication between the non-English speaking Somali
      women and health workers was perceived as an underlying problem in seeking
      information. Fears about misinterpretation and confidentiality, limit the
      usefulness of interpreters. The Somali women perceived that they were denied
      information due to punitive attitudes and prejudiced views among health
      professionals.

PMID- 11580799
TI  - Promoting teenage sexual health: an investigation into the knowledge, activities
      and perceptions of gynaecology nurses.
AB  - AIM: This study was designed to investigate the teenage sexual health service
      provided by gynaecology nurses at Queen's Medical Centre, Nottingham, United
      Kingdom (UK), by assessing their knowledge, activities and perceptions in
      relation to teenage sexual health. BACKGROUND: Part of a gynaecology nurse's work
      is caring for teenagers with sexual health problems, including unwanted
      pregnancies and sexually transmitted infections (STIs). Given the current
      national focus in the UK on improving teenage sexual health, there is clearly a
      role for gynaecology nurses to play, but this is rarely referred to in published
      literature and appears to be poorly defined. METHOD: A cross sectional survey of
      all gynaecology nurses at Queen's Medical Centre was carried out, followed by
      semi-structured interviews with a small random subsample. FINDINGS: Results
      indicated that, although 65% of nurses had worked on the gynaecology unit for
      more than 5 years, there was poor knowledge, an inconsistent pattern of nursing
      interventions and negative perceptions of the service offered. A majority of the
      nurses (87%) had not received any specific training in how to nurse teenagers
      with sexual health problems and 65% considered that the quality of sexual health
      service offered to teenagers was poor. Unexpected findings included poor general
      knowledge of local teenage sexual health services, the emotional effect on some
      nurses caring for young teenagers undergoing medical terminations of pregnancy
      (ToP), and the complete lack of training and protocols for taking a sexual
      history. CONCLUSIONS: The nurses felt that the teenage sexual health service
      provided could be improved by better staff training, better information for
      teenagers and better organization. Recommendations have been made as a result of
      the study but the staff will need management support to ensure that changes are
      effective. Generalizations cannot be drawn from a study in one hospital but the
      results could reflect the low profile given to the teenage sexual health aspect
      of gynaecology nurses' work in the UK.

PMID- 11580800
TI  - Interaction relating to privacy, identity, autonomy and security. An
      observational study focusing on a woman with dementia and "behavioural
      disturbances", and on her care providers.
AB  - AIM: The study aims to illuminate how one woman with severe dementia and so
      called behavioural disturbances acts in relation to her care providers and how
      the care providers act in relation to her. METHODS: Fourteen participant
      observations, including one woman with dementia and six care providers, were
      performed. A reflective dialogue focusing on the interaction between the woman
      and her care providers followed each observation. The tape-recorded observational
      notes and reflective dialogues were fixed as a text, which was subjected to a
      thematic content analysis. FINDINGS: The main findings are that the interaction
      between a woman with severe dementia and "behavioural disturbances" and her care
      providers relates to privacy, identity, autonomy and security. The phenomena are
      intertwined and also in conflict with each other. Interaction is a complex
      dialectic process in which those who are engaged meet problems that can be solved
      and are involved in dilemmas that cannot be solved, only related to.

PMID- 11580801
TI  - Obesity in adults and children: a call for action.
AB  - Obesity/overweight in adults and children is a worldwide health problem
      associated with substantial economic burden as measured by paid sick leave, life
      and disability insurance rates, and obesity-related physician visits and hospital
      stays. Overweight/obese people experience hypertension, elevated cholesterol, and
      type 2 diabetes and suffer more joint and mobility problems than people within
      the normal weight for height range. While there is need to understand individual
      behaviors that can be modified to promote weight loss and weight maintenance,
      there is as great a need to consider contextual factors at the societal level
      that can impede or even sabotage weight control efforts. In every country with
      improved living standards people will continue to eat too much and engage in too
      little physical activity. The call for action is for all modernized societies to
      alter environments and attitudes to support, rather than hinder, healthy dietary
      intake and being physically active.

PMID- 11580802
TI  - Chinese values, health and nursing.
AB  - PURPOSE: To describe the roots of Chinese values, beliefs and the concept of
      health, and to illustrate how these ways have influenced the development of
      health care and nursing among Chinese in the Republic of China (ROC) and the
      People's Republic of China (PRC). Scope. Based on the literature and direct
      observation in the PRC and ROC, this is an introduction to Chinese philosophies,
      religion, basic beliefs, and values with a special meaning for health and
      nursing. Chinese philosophies and religion include Confucian principles, Taoism,
      theory of "Yin" and "Yang", and Buddhism. Beliefs and values include the way of
      education, practice of acupuncture, herbal treatments and diet therapy. How
      people value traditional Chinese medicine in combination with western science,
      and the future direction of nursing and nursing inquiry are also briefly
      addressed. CONCLUSION: Chinese philosophies and religions strongly influence the
      Chinese way of living and thinking about health and health care. Nurses must
      combine information about culture with clinical assessment of the patient to
      provide cultural sensitive care. A better way may be to combine both western and
      Chinese values into the Chinese health care system by negotiating between the
      traditional values while at the same time, respecting an individual's choice. The
      foundation of China's philosophical and aesthetic tradition, in combination with
      western science is important to the future advancement of nursing research that
      will be beneficial to the Republics, Asia, and the world.

PMID- 11580803
TI  - Traditional healing in Likorrahi in the early 20th century.
AB  - AIM: The aim of this study is to record empirical data and views regarding
      health, illness, healing, hygiene, prevention and birth in a rural society at the
      beginning of the 20th century. BACKGROUND: Likorrahi was a small Greek village in
      the region of Epirus that was abandoned during the 1970s. Epirus is a rural and
      mountainous area. DESIGN: The research was conducted 10 years ago among former
      inhabitants of the community of Likorrahi. The informants were 33 Likorrahites
      over the age of 60. The research method which was used was that of ethnographic
      interviews focusing on general health issues. FINDINGS: The findings show that in
      the early 20th century different doctors, nurses and midwives offered their
      health care services free to the Likorrahites. There were few doctors, there was
      no medicine and science knew little of disease. CONCLUSIONS: This study has
      historical value for nurses and other health professionals. It will also be of
      interest to anthropologists, ethnographers and students of rural history.

PMID- 11580804
TI  - An exploration and advancement of the concept of trust.
AB  - BACKGROUND: Trust is a concept used both in everyday language and in the
      scientific realm. An exploration of the conceptualizations of trust within the
      disciplines of nursing, medicine, psychology and sociology, revealed that trust
      is an ambiguous scientific concept. AIMS: In order to increase the pragmatic
      utility of the concept of trust for scientific application, further clarification
      and development of the concept was undertaken. METHODS: First, a concept analysis
      was conducted with the aim of clarifying the state of the science of discipline
      specific conceptualizations of trust. The criterion-based method of concept
      analysis as described by Morse and colleagues was used (Morse et al. 1996a,
      1996b, Morse 2000). This analytic process enabled the assessment of the
      scientific maturity of the concept of trust. The interdisciplinary concept of
      trust was found to be immature. Based on this level of maturity it was determined
      that in order to advance the concept of trust toward greater maturity, techniques
      of concept development using the literature as data were applied. In this
      process, questions were "asked of the data" (in this case, the selected
      disciplinary literatures) to identify the conceptual components of trust.
      RESULTS: The inquiry into the concept of trust led to the development of an
      expanded interdisciplinary conceptual definition by merging the most coherent
      commonalties from each discipline. CONCLUSIONS: The newly developed
      interdisciplinary conceptualization advances the concept toward maturity, that
      is, a more refined, pragmatic and higher-order concept. The refined concept of
      trust transcends the contextual boundaries of each discipline in a truly
      interdisciplinary scientific fashion.

PMID- 11580805
TI  - Power and partnership: a critical analysis of the surveillance discourses of
      child health nurses.
AB  - AIMS: To explore surveillance discourses within New Zealand child health nursing
      and to identify whether surveillance practices have implications in this context
      for power relations. BACKGROUND: In New Zealand child health nurses are called
      Plunket nurses, who are employed by a voluntary organization, the Royal New
      Zealand Plunket Society (RNZPS). These nurses primarily work in the community
      with the families of new babies and preschool children. Their work is called
      child health surveillance and this is considered to involve routine and
      unproblematic practices, which are generally carried out in homes and clinics in
      the context of an ongoing relationship between the Plunket nurse and the mother
      of a baby. However, suggestions in the literature that surveillance, wherever it
      is practised, has implications for power relations cast doubt on official claims
      that this nurse-mother relationship is mediated through a partnership model of
      care. METHODS: Five experienced and practising Plunket nurses were each
      interviewed twice. The texts generated by these semi-structured interviews were
      analysed using a Foucauldian approach to critical discourse analysis. RESULTS: In
      contrast with the conventional view of power as held and wielded by one party,
      this study revealed that, in the Plunket nursing context, power is exercised in
      various and unexpected ways. Although the relationship between the mother and the
      nurse cannot be said to operate as a partnership, it is constituted in the
      nurses' discourses as a dynamic relationship in which the mother is actively
      engaged on her own terms. The effect of this is that it is presented by the
      nurses as a precarious relationship that has significant implications for the
      success of their work.

PMID- 11580806
TI  - Holistic symptom management: modelling the interaction phase.
AB  - AIM: This article details an interaction model that links the way a nurse
      participates in a client's effort to describe the symptom experience and the
      eventual symptom management outcome. RATIONALE: Symptoms represent more than
      clues to an underlying disease process. Within a nursing perspective, managing
      symptoms requires an understanding of the person's experience and the meaning
      associated with each symptom. All nurses engage in symptom work with clients, but
      the extent of their accountability varies within their scope of practice. In the
      United States of America (USA) model of advanced practice nursing, the scope
      expands to include all aspects of symptom management such as eliciting an
      accurate understanding, using a symptom cluster to determine underlying causes,
      and involving the client in management decisions. A holistic nursing approach to
      symptom management is particularly well suited to the increasing numbers of
      people with chronic illness. METHOD: The discussion herein details the
      interaction phase of the evolving model of Negotiated Symptom Management in
      chronic illness. Analysis of the participants, process, and context governing
      this encounter reveal the complexities of the interaction. FINDINGS: It is argued
      that variables within the interaction have the potential to compromise desired
      nurse and client outcomes. Although symptom acknowledgement and relief is a
      primary goal, the emphasis for the nurse clinician remains on the person, not the
      symptom. Effective symptom management is dependent on hearing and attending to
      the lifeworld of the client. CONCLUSION: Attending to key areas of influence in
      the interaction process facilitates the achievement of desired outcomes in
      symptom management--accurate diagnosis, symptom relief, and agreement on a course
      of action. The dominance of chronic illness in health care, and the centrality of
      the symptom experience underscores the value of sensitizing nurses to these
      issues.

PMID- 11580807
TI  - A stage planning programme model for health education/health promotion practice.
AB  - AIM: To investigate the validity of a stage planning programme model for health
      education/health promotion practice in nursing settings and to develop a specific
      model for this purpose. Background/rationale. The last decade or so has seen a
      marked increase in the amount of health educational/health promotional activities
      that nurses are expected to undertake. This has followed concerted calls to make
      health promotion a familiar and recognized part of nursing practice. Despite
      this, however, current health-related practices are still unstructured, haphazard
      and under-evaluated. This state of affairs is further compounded by the lack of
      any generic and systematic nursing planning process model by which health
      education/health promotion programmes are applied in practice. This paper puts
      forward the case for such a model, develops it, and demonstrates its possible
      application in clinical settings. METHOD: A systematic literature review was
      conducted in order to develop a new theoretical perspective for health
      promotion/health education nursing practice. The proposed model has evolved from
      this new perspective. The process of developing this model has drawn on existing
      contemporary planning models--using them as a means to develop a conceptual
      framework. Consequently, the proposed model seeks to critique, adapt and adopt
      some of their components within a nursing context. CONCLUSION: If the current
      situation continues, in which planning process models are not adopted as a
      routine part of practice, then nursing may well remain a "bystander" in health
      promotion/health education.

PMID- 11580808
TI  - Quantification of the graphical details of collagen fibrils in transmission
      electron micrographs.
AB  - A novel 2D image analysis technique is demonstrated. Using the digitized images
      of articular cartilage from transmission electron microscopy (TEM), this
      technique performs a localized 'vector' analysis at each region that is large
      enough to include several or tens of collagen fibrils but small enough to provide
      a fine resolution for the whole tissue. For each small and localized region, the
      morphology of the collagen fibrils can be characterized by three quantities
      essential to the nature of the tissue: the concentration of the fibrils, the
      overall orientation of the fibrils, and the anisotropy of the fibrils. This
      technique is capable of providing new insight to the existing technology by
      assigning quantitative attributes to the qualitative graphics. The assigned
      quantities are sensitive to the fine structure of the collagen matrix and
      meaningful in the architectural nature of the collagen matrix. These quantities
      could provide a critical linkage between the ultrastructure of the tissue and the
      macroscopic behaviours of the material. In addition, coarse-graining the
      microscopic resolution of EM without compromising the essential features of the
      tissue's structure provides a direct view of the tissue's morphology and permits
      direct correlations and comparisons among interdisciplinary techniques.

PMID- 11580809
TI  - Quantitative fractography by digital image processing: NIH Image macro tools for
      stereo pair analysis and 3-D reconstruction.
AB  - A set of NIH Image macro programs was developed to make qualitative and
      quantitative analyses from digital stereo pictures produced by scanning electron
      microscopes. These tools were designed for image alignment, anaglyph
      representation, animation, reconstruction of true elevation surfaces,
      reconstruction of elevation profiles, true-scale elevation mapping and, for the
      quantitative approach, surface area and roughness calculations. Limitations on
      time processing, scanning techniques and programming concepts are also discussed.

PMID- 11580810
TI  - Combined application of electron backscatter diffraction and stereo
      photogrammetry in fractography studies.
AB  - The main aim of this paper is to report on recent experimental developments that
      have succeeded in combining electron back-scatter diffraction (EBSD) with stereo
      photogrammetry, compared with two other methods for study of fracture surfaces,
      namely visual fractography analysis in the scanning electron microscope (SEM) and
      EBSD directly from facets. These approaches will be illustrated with data
      relating to the cleavage plane orientation analysis in a ferritic and C-Mn steel.
      It is demonstrated that the combined use of EBSD and stereo-photogrammetry
      represents a significant advance in the methodology for facet crystallography
      analysis. The results of point counting from fractograph characterization
      determined that the proportions of intergranular fracture in C-Mn and ferritic
      steels were 10.4% and 9.4%, respectively. The crystallographic orientation was
      determined directly from the fracture surface of a ferritic steel sample and
      produced an orientation distribution with a clear trend towards the [001] plane.
      A stereo-photogrammetry technique was validated using the known geometry of a
      Vickers hardness indent. The technique was then successfully employed to measure
      the macroscopic orientation of individual cleavage facets in the same reference
      frame as the EBSD measurements. Correlating the results of these measurements
      indicated that the actual crystallographic orientation of every cleavage facet
      identified in the steel specimens is [001].

PMID- 11580811
TI  - In-situ transmission electron microscopy studies of polymer-carbon nanotube
      composite deformation.
AB  - This paper demonstrates the viability of in-situ transmission electron microscopy
      for studying the deformation mechanisms of polymer nano-composites. In-situ
      straining studies are performed on carbon multiwalled nanotube (MWNT)-polystyrene
      composite films. The experiments show that load transfer across the nanotube
      polystyrene interface is operative well into the plastic deformation regime of
      the composite film. The MWNTs are observed to bridge cracks propagating through
      the polystyrene, providing closure stresses across the crack wake. Although some
      MWNTs fracture by either a sword-in-sheath mechanism or transverse shear
      fracture, most of the MWNTs eventually debond at the MWNT-polymer interface and
      subsequently pull out of the matrix.

PMID- 11580812
TI  - Artificially induced unusual shape of erythrocytes: an atomic force microscopy
      study.
AB  - We used air operating atomic force microscopy (AFM) to study several
      morphological modifications of human erythrocytes, artificially produced by
      addition of exogenous agents including phospholipids, low ionic strength media
      and drugs. Most experiments were performed on unfixed samples to avoid treating
      red blood cells (RBCs) with chemical agents that can, in principle, induce
      morphological alteration. After detailed quantitative AFM characterization, the
      artificially produced abnormally shaped RBCs were compared with cells that occur
      with high incidence in blood pathologies. This morphological approach suggests a
      new strategy to describe and understand the biochemical and/or mechanical
      modifications responsible for the underlying pathologically induced changes and
      prove AFM to be a suitable tool to study erythrocyte deformation.

PMID- 11580813
TI  - Scanning force images through the 'Milliscope'--a probe microscope with very wide
      scan range.
AB  - The effectiveness and adequacy of a home-built scanning force microscope (SFM)
      able to cover a volume of approximately 1.2 x 1.2 x 0.13 mm(3) (X x Y x Z) were
      tested on calibrating objects, as well as on cytological and histological
      samples. The instrument was designed for matching the magnification range of an
      optical microscope (approximately 20-1200x) but its dynamics were one or two
      orders of magnitude higher, thanks to a lateral resolution of about 10 nm. Images
      ranging in size from 1.2 x 1.2 mm(2) to 1 x 1 microm(2) showed a quality
      comparable to that given by other SFMs on similar materials. The 'Milliscope' is
      a curious but effective imaging tool whose operating range overlaps at one
      extreme with a goldsmith's eyepiece, and at the other with an electron
      microscope. The intrinsic limits of scanning probe techniques and of the
      available SFM cantilevers prevented us taking complete advantage of the wide
      height range of our scanner. However, our results show that an instrument having
      a very wide scan area, obtained through simple, inexpensive and intrinsically
      linear techniques, can give a good performance even at small scan sizes. This
      encourages us to develop wide scan instruments, which could further increase the
      already extensive use of scanning force microscopy in biology.

PMID- 11580814
TI  - Improved precision of quantitating calcium in biological electron probe analysis.
AB  - We describe the use of direct multiple least-squares fitting of (unfiltered)
      biological X-ray spectra. Test of this method on computer-generated spectra and
      experimental specimens shows that, for the average biological specimen, direct
      fitting improves the precision of Ca measurements by an approximate factor of 1.6
      for a given electron dose. The influence of non-statistical, instrumental sources
      of measurement errors is considered, and we show a simple method for reducing the
      effect of these sources of error in the directly fitted spectra.

PMID- 11580815
TI  - A new sample preparation method for biological soft X-ray microscopy: nitrogen
      based contrast and radiation tolerance properties of glycol methacrylate-embedded
      and sectioned tissue.
AB  - We describe the preparation of a biological tissue for imaging in a transmission
      soft X-ray microscope. Sections of exocrine pancreas embedded in glycol
      methacrylate polymer, an embedding medium widely used in visible light and
      electron microscopy, were examined. Contrast was based primarily on the nitrogen
      content of the tissue, and dual-wavelength imaging at the nitrogen K-shell
      absorption edge was used to map the distribution and provide quantitative
      densitometry of both the protein and embedding matrix components of the sample.
      The measurements were calibrated by obtaining the absorption spectrum of protein
      near the nitrogen edge. The contrast was consistent and reproducible, making
      possible the first large-scale X-ray microscopic study on sections of plastic
      embedded soft tissue. At radiation doses of up to 10(8) Gray, much more than
      required for routine imaging, no distortion and little mass loss were observed.
      This sample preparation method should permit routine imaging of tissues in X-ray
      microscopes, previously a difficult task, as well as multimodal imaging (using
      visible light, X-ray, electron, and scanned probe microscopies) on the same
      sample.

PMID- 11580816
TI  - A simple method for SEM examination of sectioned diatom frustules.
AB  - We describe an innovative yet straightforward method to obtain high quality thin
      sections of diatom exoskeletons for observation by scanning electron microscopy
      (SEM). The use of this new technique allows for clear observations of some
      ultrastructural valve features, including the raphe, which are generally
      difficult to observe and describe accurately using transmission electron
      microscopy analysis of thin sections or SEM of randomly fractured diatom valves.
      In addition, because this method involves the complete removal of the organic
      content of the diatom cells, resulting in clean and mostly undisturbed skeletal
      thin cross-sections, even the intact valvar structures of weak girdle bands can
      be studied.

PMID- 11580817
TI  - Colour reproducibility of a photo-activated prosthetic composite with different
      thicknesses.
AB  - This study determined the colour accuracy of a photo-activated prosthetic
      composite with various thicknesses and shades for the purpose of evaluating the
      relationship between material thickness variation and colour reproducibility.
      Four light shades (A1, B1, C1 and D2) and four dark shades (A4, B4, C4 and D4) of
      a representative photo-activated prosthetic composite (Artglass) for body paste
      were assessed. The specimens were prepared with thicknesses of 0.5, 1.0, 1.5,
      2.0, 2.5 and 3.0 mm. The L*a*b* colour parameter of each shade was measured using
      a dental colorimeter (ShadeEye) connected to a computer. The overall colour
      accuracy of groups of five specimens was compared by means of analysis of
      variance (ANOVA) and Scheffe's S multiple range test (P=0;05). In addition,
      L*a*b* colour difference (Delta E*) values between the 3.0 mm thickness and the
      other thicknesses were calculated. Three-factor ANOVA revealed that all colour
      parameters were influenced by the thickness as well as by the shade letter and
      shade tab (P < 0.05). The L* value consistently decreased for all shades as
      thickness increased, although there was no obvious correlation between the
      thickness of the material and either the a* or b* values. Among the Delta E*
      values, the values between the 2.5 and 3.0 mm thicknesses were the lowest, and
      values were found to be lower than 2.0 for all shades. The colour accuracy of the
      photo-activated prosthetic composite was related to the thickness of the material
      regardless of the shade. For acceptable colour reproducibility, a composite
      material thickness of at least 2.5 mm was found to be required.

PMID- 11580818
TI  - Effects of surface treatments on bond strength of glass-infiltrated ceramic.
AB  - The purpose of this study was to evaluate the effects of various surface
      treatments on the bond strength at the In-Ceram/resin composite interface. Ninety
      eight In-Ceram specimens were divided into seven groups and exposed to various
      surface treatments as follows: (A) control (B) saliva contamination (C) saliva
      contamination plus aluminum oxide sandblasting (D) glove powder contamination (E)
      glove powder contamination plus aluminum oxide sandblasting (F) rough aluminum
      oxide sandblasting and (G) excess glass infiltration. A resin composite cylinder
      was cemented to each In-Ceram specimen with Panavia 21 resin luting cement. Half
      of the cemented specimens in each group were stored in water for 24 h, and the
      other half were stored in water for 2 weeks and then were thermo-cycled for 2000
      cycles. Shear bond strengths (SBS) of seven specimens in each subgroup were
      determined and analysed using analysis of variance (ANOVA) and Tukey HSD test as
      well as Student's t-test. Scanning electronic microscopy was used to identify the
      type of bond failure. Shear bond strength was significantly decreased by saliva
      and glove powder contaminations (P < 0.05). Sandblasting treatment did not
      improve the saliva-contaminated specimens. However, the glove powder plus
      sandblasting group showed no significant difference in SBS compared with the
      control group. There was no significant difference in SBS between the excess
      glass-infiltrating group and the control group. The SBS was significantly
      decreased by rough aluminum oxide sandblasting (P < 0.05). The SBS values of
      groups without thermocycling were significantly greater than those of groups with
      thermocycling (P < 0.05). There were no significant differences among SBS values
      of the seven groups with thermocycling. Combined cohesive and adhesive bond
      failures were seen in every group. Various surface treatments or contaminants may
      significantly influence the bond strength of In-Ceram restorative in clinical
      use.

PMID- 11580819
TI  - Tensile bond strengths of four different dentin adhesives on irradiated and non
      irradiated human dentin in vitro.
AB  - This study evaluated the influence of irradiation on dentin bond strength. Sixty
      irradiated and 60 non-irradiated human third molars were used. The irradiation
      dose of 60 Gy was fractionally applied over 6 weeks (2 Gy day(-1), 5 days week(
      1). All teeth were prepared in a special manner allowing the simulation of intra
      pulpal pressure and dentin perfusion. Dentin specimens with a thickness of 2.0 mm
      were obtained under standardized conditions. The specimens were randomly assigned
      to four experimental groups. Tensile bond strength of four different dentin
      bonding agents (Scotchbond 1, Solobond Plus, Prime&Bond 2.1 and Syntac) was
      evaluated using an Instron Universal testing machine. Pairwise comparison did not
      show any significant differences between the irradiated and non-irradiated
      groups. The influence of the different dentin adhesives was significant
      (P=0.0001; ANOVA). Compared with Solobond Plus and Prime&Bond 2.1, the use of
      Scotchbond 1 resulted in a significantly higher tensile bond strength in non
      irradiated specimen (P< 0.05; closed test procedure based on Kruskal-Wallis
      test). Within the limitations of an in vitro study, it can be concluded that
      adhesive restoration procedures can be successfully used in patients irradiated
      for cancer of the head and neck.

PMID- 11580820
TI  - Obturator prostheses for hemimaxillectomy patients.
AB  - Maxillary defects are created by surgical treatment of benign or malignant
      neoplasms, congenital malformation and by trauma. The size and location of the
      defects influence the degree of impairment and difficulty in prosthetic
      rehabilitation. Lack of support, retention, and stability are common
      prosthodontic treatment problems for patients who have had a maxillectomy. A
      prosthesis used to close a palatal defect in a dentate or edentulous mouth is
      referred to as an obturator. The obturator prosthesis is used to restore
      masticatory function and improve speech, deglutition and cosmetics for maxillary
      defect patients.

PMID- 11580821
TI  - Different responses of masticatory movements after alteration of occlusal
      guidance related to individual movement pattern.
AB  - We hypothesized that the motor response of the masticatory system to peripheral
      inputs varies according to the functional potential of an individual. The
      specific aim of the present study was to determine whether individually different
      types of masticatory patterns, especially with respect to the closing movement
      pattern, would produce different motor responses to an alteration of occlusal
      guidance. The inclination of the occlusal guidance was steepened by approximately
      10 degrees by attaching a metal overlay to the lingual surface of the maxillary
      working-side canine. The masticatory movements of 20 young adults were measured
      using a three-dimensional mandibular movement analysis system before and after
      the alteration of occlusal guidance. The individual masticatory patterns were
      divided into two groups based on the closing movement pattern before the
      alteration of occlusal guidance, i.e. vertical and lateral types. The alteration
      of occlusal guidance significantly influenced the masticatory closing angle,
      closing time, occlusal time, the stability of the opening angle and the cycle
      time in the lateral-type group (n = 9, paired t-test; P < 0;05), while no
      significant changes were found in the vertical-type group (n = 11). These
      differences in motor response between the two groups were not found in the
      overall analysis of all the 20 subjects. We concluded that the oral motor
      response to the alteration of occlusal guidance depends on the individual
      masticatory movement pattern. Because the present analysis of subgroups of the
      subjects revealed motor response findings different from those in the overall
      analysis of all the 20 subjects, such potential subgroupings should be considered
      as an attempt to identify a specific effect of peripheral inputs on masticatory
      function in humans.

PMID- 11580822
TI  - The relationship of bruxism with craniofacial pain and symptoms from the
      masticatory system in the adult population.
AB  - The association of bruxism with craniofacial pain and symptoms of dysfunction of
      the masticatory system was assessed in a sample of 483 adult subjects, aged 18-75
      years and selected from the general population living in the municipality of
      Segrate, a metropolitan area in northern Italy. Subjects were interviewed by a
      questionnaire about oral conditions, occurrence of symptoms of masticatory
      disturbances, craniofacial and neck pain. The overall prevalence of bruxism was
      31;4% (95% confidence interval (CI): 27;3-35;5%). At univariate analysis bruxism
      was significantly associated with craniofacial pain, difficulty in closing the
      mouth, difficulty in opening the mouth wide or in locking the mouth,
      temporomandibular joint sounds, pain on movement, a feeling of stiffness or
      fatigue of the jaws, and neck pain. After adjustment for reciprocal influences
      and confounding variables, logistic regression analysis disclosed a strong
      independent association of bruxism with difficulty in closing the mouth (adjusted
      odds ratio, (OR): 2;84, 95% CI: 1;68-4;48), and a weaker relationship with
      craniofacial pain (adjusted OR: 1;84, 95% CI: 1;16-2;93) and temporomandibular
      joint sounds (adjusted OR: 1;64, 95% CI: 1;00-2;69). The findings show that in
      the general adult population there is a complex connection among bruxism,
      craniofacial pain and symptoms of masticatory disturbances. Furthermore, they
      suggest that the most direct relationship of bruxism may be with difficulties in
      mouth movements, but also an independent association may exist with craniofacial
      pain and other symptoms of temporomandibular disorder.

PMID- 11580823
TI  - A comparison of the muscular relaxation effect of TENS and EMG-biofeedback in
      patients with bruxism.
AB  - This study investigated effects of electromyographic (EMG) biofeedback (BFB) and
      transcutaneous electrical neuromuscular stimulation (TENS) on the EMG activity of
      the masticatory muscles and skin conductance level (SCL) of patients, suffering
      from myofacial pain syndrome. In the course of the investigation, EMG activity as
      well as the SCL was measured after a 20 min BFB or, respectively, after a
      myomonitor session in 20 patients and pre- and post-treatment values were
      compared. Results showed tendencies of decreased mean-EMG levels for both groups
      after the treatment sessions, with higher EMG values for the myomonitor group.
      There was no indication of a significant decrease in mean EMG levels over the
      sessions. Furthermore, an increase of the SCL during the period of treatment was
      observed for both groups in session I and II, while session III produced nearly
      stable values. No existing correlations for changes in SCL and EMG-activity could
      be established.

PMID- 11580824
TI  - Direct tensile strength of visible light-cured restorative materials containing
      fluoride.
AB  - The purpose of this study was to compare the fluoride release and direct tensile
      strength at 24 h, 1 month, and 3 months of two conventional glass-ionomers, two
      visible light-cured resin-modified glass-ionomers, a polyacid resin composite and
      two resin composites. The results were statistically analysed using ANOVA and
      Fisher's PLSD at alpha=0.05. The data on fluoride release indicated that the
      immersion period (24 h, 1 month, and 3 months) significantly influenced the
      cumulative amount of fluoride released (P < 0.001). The direct tensile strengths
      after 1 month of storage were significantly higher than those after 24 h or 3
      months of storage (P < 0.001). Thus, the cements and resins were not weakened by
      the loss of fluoride. Conventional glass-ionomer cement showed the lowest direct
      tensile strength. Resin-modified glass-ionomer behaved in between the resin
      composites and conventional glass-ionomers in terms of all three testing times,
      however, the polyacid resin composites most closely resembled the resin
      composites. The polyacid resin composites had greatly enhanced direct tensile
      strength, however, this material also reduced the fluoride availability.

PMID- 11580825
TI  - The effect of pH on the erosion of dentine and enamel by dietary acids in vitro.
AB  - The reported incidence of tooth erosion caused by acidic soft drinks has been
      increasingly documented. Citric and phosphoric acids are the two main dietary
      acids present in these soft drinks. Many variables need to be determined in order
      to assess risk factors for dental erosion caused by beverage consumption
      including pH, titratable acidity, pKa, buffering capacity, hence the aim of these
      in vitro investigations. Methodologies included profiling flat enamel and dentine
      samples (< +/- 0.3 microm profile) from unerupted human third molars. Groups of
      five specimens were placed in acidic solutions adjusted with alkali over the
      available pH range; citric, phosphoric and hydrochloric acid were adjusted with
      sodium hydroxide and citric acid with trisodium citrate. Tissue loss was
      calculated by profilometry. Results showed that under these conditions citric
      acid caused far more erosion over the pH range employed than phosphoric acid for
      both tissue types. Citric acid compared with hydrochloric acid highlighted
      dissolution and chelation effects. Phosphoric acid caused minimal erosion over pH
      3 for enamel and pH 4 for dentine. These factors could be considered in order to
      reduce the erosivity of acidic soft drinks.

PMID- 11580826
TI  - The effect of the addition of surface treated chopped and continuous poly (methyl
      methacrylate) fibres on some properties of acrylic resin.
AB  - Poly (methyl methacrylate), the material most commonly used in the construction
      of dentures, is not without limitations particularly in terms of mechanical
      strength, such as flexural and fatigue strength. The Dental Practice Board for
      England statistics show that many dentures fail as a result of fracture. This
      study investigated the self-reinforcement of acrylic resin through the addition
      of surface treated poly (methyl methacrylate) fibres in chopped and continuous
      form. The effect of the addition of fibres on transverse and impact strengths was
      investigated. The addition of surface treated chopped or continuous fibres to
      acrylic resin did not improve the transverse or impact strengths. The addition of
      surface treated poly (methyl methacrylate), in the present form, to acrylic resin
      cannot be recommended as a method of reinforcement.

PMID- 11580827
TI  - Activity of jaw-opening and jaw-closing muscles and their influence on
      dentofacial morphological features in normal adults.
AB  - The purpose of this study was to determine the relationship between the
      dentofacial morphology and the function of masticatory muscles estimated by
      kinesiological measurements during isotonic jaw-opening (O) and closing (C)
      muscle contractions. We examined 26 male adult subjects who had no history of
      masticatory dysfunction. Three kinesiological parameters, the maximum force
      (F(max)), maximum velocity (V(max)) and maximum power (P(max)) were measured in
      both O and C muscles. Correlation analysis was performed between these parameters
      and dentofacial morphological features determined on lateral roentgenographic
      cephalograms. The F(max) (C), V(max) (O), log O/C of V(max), and P(max) (O)
      significantly correlated with anterior overbite. P(max) (C) significantly and
      negatively correlated with SN-ArG. Furthermore, log O/C of P(max) significantly
      and negatively correlated with SNA, SNB and ArG/GMe, and positively with SN-ArG.
      These results, combined with our previous findings that electromyographic muscle
      activity during isometric contraction correlated significantly with mandibular
      morphology, indicate that the dentofacial morphology is influenced by the
      function of both O and C muscles.

PMID- 11580828
TI  - Comparison of cell proliferation on modified dental ceramics.
AB  - The aim of this study was to investigate the influence of substrate
      characteristics such as chemical composition and surface morphology of dental
      ceramics to support cell attachment and proliferation. Thus, body (B) and
      shoulder (S) porcelain differing on their surface morphology and composition were
      treated with oxides CaO or CaO and P(2)O(5) and four modified ceramics BCa, BCaP,
      SCa, SCaP were constructed, respectively. The modified ceramics differ from their
      controls concerning their surface morphology as evaluated by Scanning Electron
      Microscope (SEM), and their surface chemical composition (Na, KP and Ca) as
      evaluated by Energy Dispersing Spectroscopy (EDS). All modified ceramics support
      better than the control ceramics the cell proliferation over 72 h incubation
      period. Furthermore, higher rates of cell proliferation was detected in shoulder
      modified ceramics (SCa and SCaP) than in all other cases.

PMID- 11580829
TI  - Influences of occlusal and skeletal discrepancies on biomechanical environment in
      the TMJ during maximum clenching: an analytic approach with the finite element
      method.
AB  - The purpose of this study was to investigate the influences of occlusal and
      skeletal discrepancies on temporomandibular joint (TMJ) stresses during maximum
      clenching. A three-dimensional (3-D) finite element model of the mandible
      including the TMJ was developed as a standard model. Furthermore, nine modified
      models were established; one dentoalveolar open bite model and eight skeletal
      open bite models with varying gonial angles or mandibular plane angles (FMAs).
      For the dentoalveolar open bite model, the TMJ stresses were larger than those
      for the standard model, although the distribution pattern was not essentially
      varied. In the skeletal open bite model with greater gonial angle or FMA, the TMJ
      stresses were significantly larger than those in the dentoalveolar open bite
      model. In conclusion, the TMJ stress was affected by occlusal and/or skeletal
      discrepancies, if coexisted in particular, indicating the association with
      degenerative changes of the TMJ components.

PMID- 11580831
TI  - Mutation of specific acidic residues of the CNF1 T domain into lysine alters cell
      membrane translocation of the toxin.
AB  - The Rho-GTPases-activating toxin CNF1 (cytotoxic necrotizing factor 1) delivers
      its catalytic activity into the cytosol of eukaryotic cells by a low pH membrane
      translocation mechanism reminiscent of that used by diphtheria toxin (DT). As DT,
      CNF1 exhibits a translocation domain (T) containing two predicted hydrophobic
      helices (H1-2) (aa 350-412) separated by a short peptidic loop (CNF1-TL) (aa 373
      386) with acidic residues. In the DT loop, the loss of charge of acidic amino
      acids, as a result of protonation at low pH, is a critical step in the transfer
      of the DT catalytic activity into the cytosol. To determine whether the CNF1 T
      domain operates similarly to the DT T domain, we mutated several ionizable amino
      acids of CNF1-TL to lysine. Single substitutions such as D373K or D379K strongly
      decreased the cytotoxic effect of CNF1 on HEp-2 cells, whereas the double
      substitution D373K/D379K induced a nearly complete loss of cytotoxic activity.
      These single or double substitutions did not modify the cell-binding, enzymatic
      or endocytic activities of the mutant toxins. Unlike the wild-type toxin, single-
      or double-substituted CNF1 molecules bound to the HEp-2 plasma membrane could not
      translocate their enzymatic activity directly into the cytosol following a low pH
      pulse.

PMID- 11580832
TI  - Environmental control of invasin expression in Yersinia pseudotuberculosis is
      mediated by regulation of RovA, a transcriptional activator of the SlyA/Hor
      family.
AB  - Invasin is the primary invasive factor of Yersinia pseudotuberculosis that allows
      efficient internalization into eukaryotic cells. We investigated invasin
      expression and found that the inv gene is regulated in response to a variety of
      environmental signals, such as temperature, growth phase, nutrients, osmolarity
      and pH, and requires the product of rovA, a member of the SlyA/Hor
      transcriptional activator family. The rovA gene was found by a genetic
      complementation strategy that restores temperature regulation of an unexpressed
      inv-phoA fusion in Escherichia coli K-12. RovA plays a role in the invasion of Y.
      pseudotuberculosis into mammalian cells and mediates the regulation of invasin in
      response to all environmental signals analysed. Deletion analysis of the inv
      promoter region revealed a DNA segment extending 207 bp upstream of the
      transcriptional start site, which is required for maximal RovA-induced inv
      transcription. Gel retardation assays showed that RovA interacts preferentially
      with this promoter fragment and suggested two potential RovA binding sites.
      Studies with chromosomal gene fusions also demonstrated that rovA follows the
      same pattern of regulation as invasin, indicating that environmental control of
      inv expression is mainly mediated by the control of RovA synthesis. Furthermore,
      we showed that a rovA-lacZ fusion is only slightly expressed in a rovA mutant
      strain, indicating that a positive autoregulatory mechanism is also involved in
      rovA expression.

PMID- 11580833
TI  - cDNA-AFLP analysis unravels a genome-wide hrpG-regulon in the plant pathogen
      Xanthomonas campestris pv. vesicatoria.
AB  - The Hrp type III protein secretion system is essential for pathogenicity of the
      Gram-negative plant pathogen Xanthomonas campestris pv. vesicatoria. Expression
      of the hrp gene cluster is controlled by HrpG, a two-component response
      regulator, and HrpX, an AraC-type transcriptional activator. Using the cDNA-AFLP
      technique, 30 hrpG-induced (hgi) and five hrpG-repressed (hgr) cDNA fragments
      were identified, defining a large hrpG-regulon in X. campestris pv. vesicatoria.
      Expression of most genes in the hrpG-regulon was dependent on hrpX. Seven cDNA
      fragments map to the known hrp gene cluster and flanking regions. All other genes
      appear to be scattered over the chromosome and endogenous plasmids. Sequence
      analysis identified genes encoding putative extracellular proteases, a putative
      transcriptional regulator and XopJ and XopB (Xanthomonas outer proteins),
      homologues of YopJ from Yersinia spp. and the avirulence protein AvrPphD of
      Pseudomonas syringae respectively. XopB is secreted by the Hrp type III secretion
      system. Analysis of deletion mutants in several hgi genes revealed a new
      virulence locus. This study demonstrates that cDNA-AFLP is a powerful tool to
      study prokaryotic transcriptomes and to identify genes contributing to
      Xanthomonas virulence and putative effector proteins.

PMID- 11580834
TI  - The carboxy-terminus of VirE2 from Agrobacterium tumefaciens is required for its
      transport to host cells by the virB-encoded type IV transport system.
AB  - Agrobacterium tumefaciens transfers DNA from the resident 'tumour-inducing' (Ti)
      plasmid into plant cells, where it can be stably integrated into the plant
      genome, ultimately resulting in crown gall tumour formation. The mobilized DNA
      molecule is a single-stranded intermediate with VirD2 covalently bound to its 5'
      end. Successful transport of the transferred DNA (T-DNA) and integration of the
      DNA into the genome requires that additional proteins be transported to the plant
      as well, including the single-stranded (ss)DNA-binding protein, VirE2. The
      transport of these two different substrates occurs as a result of the activities
      of a type IV secretion system encoded by the virB operon. Although the substrates
      have been identified, the mechanism of their transport remains unknown. In the
      experiments described here, a region in one of these substrates, VirE2, necessary
      for transport is identified. The addition of a C-terminal FLAG epitope tag to
      VirE2, or the deletion of its C-terminal 18 amino acids, renders it non
      functional in A. tumefaciens. However, transgenic plants expressing either of
      these virE2 genes respond to virE2 mutants of A. tumefaciens by forming wild-type
      tumours. These results indicate that this region of VirE2 is necessary for the
      protein to be transported into the plant cells, but is not necessary for its
      function within the plant. Additionally, these studies demonstrate that mutant
      forms of VirE2 lacking this region do not disrupt the activities of the VirB
      transporter and support the hypothesis that VirE2 and the VirD2 T-strand are
      transported independently, even when they co-exist in the same cell.

PMID- 11580835
TI  - Topological and functional characterization of WbpM, an inner membrane UDP-GlcNAc
      C6 dehydratase essential for lipopolysaccharide biosynthesis in Pseudomonas
      aeruginosa.
AB  - WbpM is essential for the biosynthesis of B-band lipopolysaccharide (LPS) in many
      serotypes of Pseudomonas aeruginosa. Homologues that can functionally complement
      a wbpM null mutant and that are also necessary for virulence have been identified
      in numerous pathogenic bacteria. WbpM and most of its homologues are large
      membrane proteins, which has long hampered the elucidation of their biochemical
      function. This paper describes the detailed characterization of WbpM using both
      in vivo and in vitro approaches. LacZ and PhoA fusion experiments showed that
      WbpM was anchored to the inner membrane via four N-terminal transmembrane
      domains, whereas the C-terminal catalytic domain resided in the cytoplasm.
      Although the membrane domains did not have any catalytic activity,
      complementation experiments suggested that they were important for the
      polymerization of high-molecular-weight B-band LPS. The biochemical
      characterization of a soluble truncated form of WbpM, His-S262, showed that WbpM
      was a C6 dehydratase specific for UDP-GlcNAc. It exhibited unusual low
      temperature (25-30 degrees C) and high pH (pH 10) optima. Although WbpM possessed
      an altered catalytic triad composed of SMK as opposed to SYK commonly found in
      other dehydratases, its catalysis was very efficient, with a kcat of 168 min(-1)
      and a kcat/Km of 58 mM(-1) min(-1). These unusual physico-kinetic properties
      suggested a potentially different mechanism of C6 dehydration for WbpM and its
      large homologues. His-S262 is now a precious tool for further structure-function
      studies.

PMID- 11580836
TI  - Lre1 affects chitinase expression, trehalose accumulation and heat resistance
      through inhibition of the Cbk1 protein kinase in Saccharomyces cerevisiae.
AB  - The addition of glucose to derepressed cells of the yeast Saccharomyces
      cerevisiae triggers activation of the cAMP pathway with a rapid drop in stress
      resistance as a consequence. We have isolated the LRE1 gene as a multicopy
      suppressor of glucose-induced loss of heat resistance. Overexpression of LRE1 in
      a wild-type strain causes the same phenotype as observed in strains with reduced
      activity of the cAMP-PKA pathway: higher heat resistance and enhanced trehalose
      levels. Deletion of LRE1 results in the opposite phenotypes. Epistasis analysis
      indicates that these effects are independent of cAMP and PKA, of the protein
      kinases Yak1, Sch9 and Rim15 and of the transcription factors Msn2 and Msn4. Lre1
      has recently been isolated in a two-hybrid screen using the conserved protein
      kinase Cbk1 as a bait. Cbk1 controls the expression of CTS1 (encoding chitinase)
      through the transcription factor Ace2. We demonstrate here that overexpression of
      LRE1 represses CTS1 whereas deletion of LRE1 induces the expression of CTS1.
      Repression of CTS1 results in deficient cell separation as a result of
      inefficient degradation of the chitin ring after cytokinesis. Neither deletion
      nor overexpression of LRE1 has any effect on CTS1 expression in a cbk1Delta
      mutant, indicating that Lre1 inhibits Cbk1. In addition, we show that increased
      trehalose accumulation and increased heat resistance caused by overexpression of
      LRE1 are also the result of inhibition of Cbk1, revealing a novel control pathway
      for certain targets affected by PKA. The yeast genome contains a homologue of
      LRE1, YDR528w, which we have called HLR1 (for homologue of Lre1). Deletion and
      overexpression of HLR1 causes similar but less pronounced effects compared with
      LRE1.

PMID- 11580837
TI  - The promoter of the operon encoding the F0F1 ATPase of Streptococcus pneumoniae
      is inducible by pH.
AB  - The genes encoding the subunits of the F0F1 membrane ATPase of Streptococcus
      pneumoniae were cloned and sequenced. The eight genes, transcribed to one mRNA,
      are organized in an operon encoding the c, a, b, delta, alpha, gamma, beta and
      epsilon subunits of 66, 238, 165, 178, 501, 292, 471 and 139 amino acid residues,
      respectively, that were expressed in an Escherichia coli system. To investigate
      the role of the ATPase in the regulation of the intracellular pH, the expression
      of the operon between pH 5.7 and 7.5 was studied. An increase in both the ATPase
      activity and the amount of the alpha and beta F1 subunits as shown by Western
      blot analysis was observed as the pH decreased. These increases were accompanied
      by an increase in the atp-specific mRNA, as shown by Northern blot and slot-blot
      analysis. Primer extension experiments and transcriptional fusions between the
      atp promoter and the reporter cat gene demonstrated that this pH-dependent
      increase in the mRNA was regulated at the level of initiation of transcription.
      Transcription of the operon occurs from a promoter with a consensus -35 box
      (TTGACA) and a -10 box (TACACT) that differs from the consensus (TATAAT). A point
      mutation at the -10 box of the promoter (change to TGCACT) avoided this increase,
      suggesting a role for this sequence in the pH-inducible regulation.

PMID- 11580838
TI  - Failure to farnesylate Rheb protein contributes to the enrichment of G0/G1 phase
      cells in the Schizosaccharomyces pombe farnesyltransferase mutant.
AB  - Protein farnesylation is important for a number of physiological processes,
      including proliferation and cell morphology. The Schizosaccharomyces pombe
      mutant, cpp1-, defective in farnesylation, exhibits distinct phenotypes,
      including morphological changes and sensitivity to the arginine analogue,
      canavanine. In this work, we report a novel phenotype of this mutant, enrichment
      of G0/G1 phase cells. This phenotype results mainly from the inability to
      farnesylate the Rheb G-protein, as normal cell cycle progression can be restored
      to the mutant by expressing a mutant form of SpRheb (SpRheb-CVIL) that can bypass
      farnesylation. In contrast, a farnesylation-defective mutant of SpRheb (SpRheb
      SVIA) is incapable of restoring the normal cell cycle profile to the cpp1-
      mutant. Inhibition of SpRheb expression leads to the accumulation of cells at the
      G0/G1 phase of the cell cycle. This growth arrest phenotype of the sprheb-
      disruption can be complemented by the introduction of wild-type sprheb+. The
      complementation is dependent on farnesylation, as the farnesylation-defective
      SpRheb-SVIA mutant is incapable of complementing the sprheb- disruption. Other
      mutants of SpRheb, E40K and S20N, are also incapable of complementing the sprheb-
      disruption. Furthermore, efficient complementation can be obtained by the
      expression of human Rheb but not Saccharomyces cerevisiae Rheb. Our findings
      suggest that protein farnesylation is important for cell cycle progression of S.
      pombe cells and that farnesylated SpRheb is critical in this process.

PMID- 11580839
TI  - EmtA, a rRNA methyltransferase conferring high-level evernimicin resistance.
AB  - Enterococcus faecium strain 9631355 was isolated from animal sources on the basis
      of its resistance to the growth promotant avilamycin. The strain also exhibited
      high-level resistance to evernimicin, a drug undergoing evaluation as a
      therapeutic agent in humans. Ribosomes from strain 9631355 exhibited a dramatic
      reduction in evernimicin binding, shown by both cell-free translation assays and
      direct-binding assays. The resistance determinant was cloned from strain 9631355;
      sequence alignments suggested it was a methyltransferase and therefore it was
      designated emtA for evernimicin methyltransferase. Evernimicin resistance was
      transmissible and emtA was localized to a plasmid-borne insertion element.
      Purified EmtA methylated 50S subunits from an evernimicin-sensitive strain 30
      fold more efficiently than those from a resistant strain. Reverse transcription
      identified a pause site that was unique to the 23S rRNA extracted from resistant
      ribosomes. The pause corresponded to methylation of residue G2470 (Escherichia
      coli numbering). RNA footprinting revealed that G2470 is located within the
      evernimicin-binding site on the ribosome, thus providing an explanation for the
      reduced binding of the drug to methylated ribosomes.

PMID- 11580840
TI  - Feedback regulation of the Bradyrhizobium japonicum nodulation genes.
AB  - Lipochitin Nod signals are produced by rhizobia and are required for the
      establishment of a nitrogen-fixing symbiosis with a legume host. The nodulation
      genes encode products required for the synthesis of this signal and are induced
      in response to plant-produced flavonoid compounds. The addition of chitin and
      lipo-chitin oligomers to Bradyrhizobium japonicum cultures resulted in a
      significant reduction in the expression of a nod-lacZ fusion. Intracellular
      expression of NodC, encoding a chitin synthase, also reduced nod gene expression.
      In contrast, expression of the ChiB chitinase increased nod gene expression. The
      chain length of the oligosaccharide was important in feedback regulation, with
      chitotetraose molecules the best modulators of nod gene expression. Feedback
      regulation is mediated by the induction of nolA by chitin, resulting in elevated
      levels of the repressor protein, NodD2.

PMID- 11580841
TI  - The ubc2 gene of Ustilago maydis encodes a putative novel adaptor protein
      required for filamentous growth, pheromone response and virulence.
AB  - The Basidiomycete fungus Ustilago maydis causes corn smut disease and alternates
      between a budding haploid saprophyte and a filamentous dikaryotic pathogen.
      Previous work demonstrated that haploid adenylate cyclase (uac1) mutants display
      a constitutively filamentous phenotype. Suppressor mutants of a uac1 disruption
      strain, named ubc for Ustilago bypass of cyclase, no longer require cAMP for the
      budding morphology. The ubc2 gene was isolated by complementation and is required
      for filamentous growth. The deduced amino acid sequence encoded by ubc2 shows
      localized homology to Sterile Alpha Motif (SAM), Ras Association (RA) and Src
      homology 3 (SH3) protein-protein interaction domains. A K78E missense mutation
      within the SAM domain, revealed a genetic interaction between ubc2 and ubc4, a
      pheromone-responsive MAP kinase kinase kinase. This indicates involvement of ubc2
      in the pheromone-responsive MAP kinase cascade and ubc2 is required for pheromone
      responsive morphogenesis. The ubc2 gene is a critical virulence factor. Thus,
      ubc2 encodes a putative novel adaptor protein that may act directly upstream of
      the pheromone-responsive MAP kinase cascade in U. maydis.

PMID- 11580842
TI  - Sites of positive and negative regulation in the Bacillus subtilis
      antiterminators LicT and SacY.
AB  - The Bacillus subtilis homologous transcriptional antiterminators LicT and SacY
      control the inducible expression of genes involved in aryl beta-glucoside and
      sucrose utilization respectively. Their RNA-binding activity is carried by the N
      terminal domain (CAT), and is regulated by two similar C-terminal domains (PRD1
      and PRD2), which are the targets of phosphorylation reactions catalysed by the
      phosphoenolpyruvate: sugar phosphotransferase system (PTS). In the absence of the
      corresponding inducer, LicT is inactivated by BglP, the PTS permease (EII)
      specific for aryl beta-glucosides, and SacY by SacX, a negative regulator
      homologous to the EII specific for sucrose. LicT, but not SacY, is also subject
      to a positive control by the general PTS components EI and HPr, which are thought
      to phosphorylate LicT in the absence of carbon catabolite repression.
      Construction of SacY/LicT hybrids and mutational analysis enabled the location of
      the sites of this positive regulation at the two phosphorylatable His207 and
      His269 within LicT-PRD2, and suggested that the presence of negative charges at
      these sites is sufficient for LicT activation in vivo. The BglP-mediated
      inhibition process was found to essentially involve His100 of LicT-PRD1, with
      His159 of the same domain playing a minor role in this regulation. In vitro
      experiments indicated that His100 could be phosphorylated directly by the general
      PTS proteins, this phosphorylation being stimulated by phosphorylated BglP. We
      confirmed that, similarly, the corresponding conserved His99 residue in SacY is
      the major site of the negative control exerted by SacX on SacY activity. Thus,
      for both antiterminators, the EII-mediated inhibition process seems to rely
      primarily on the presence of a negative charge at the first conserved histidine
      of the PRD1.

PMID- 11580843
TI  - The pavA gene of Streptococcus pneumoniae encodes a fibronectin-binding protein
      that is essential for virulence.
AB  - Streptococcus pneumoniae colonizes the nasopharynx in up to 40% of healthy
      subjects, and is a leading cause of middle ear infections (otitis media),
      meningitis and pneumonia. Pneumococci adhere to glycosidic receptors on
      epithelial cells and to immobilized fibronectin, but the bacterial adhesins
      mediating these reactions are largely uncharacterized. In this report we describe
      a novel pneumococcal protein PavA, which binds fibronectin and is associated with
      pneumococcal adhesion and virulence. The pavA gene, present in 64 independent
      isolates of S. pneumoniae tested, encodes a 551 amino acid residue polypeptide
      with 67% identical amino acid sequence to Fbp54 protein in Streptococcus
      pyogenes. PavA localized to the pneumococcal cell outer surface, as demonstrated
      by immunoelectron microscopy, despite lack of conventional secretory or cell
      surface anchorage signals within the primary sequence. Full-length recombinant
      PavA polypeptide bound to immobilized human fibronectin in preference to fluid
      phase fibronectin, in a heparin-sensitive interaction, and blocked binding of
      wild-type pneumococcal cells to fibronectin. However, a C-terminally truncated
      PavA' polypeptide (362 aa residues) failed to bind fibronectin or block
      pneumococcal cell adhesion. Expression of pavA in Enterococcus faecalis JH2-2
      conferred > sixfold increased cell adhesion levels to fibronectin over control
      JH2-2 cells. Isogenic mutants of S. pneumoniae, either abrogated in PavA
      expression or producing a 42 kDa C-terminally truncated protein, showed up to 50%
      reduced binding to immobilized fibronectin. Inactivation of pavA had no effects
      on growth rate, cell morphology, cell-surface physico-chemical properties,
      production of pneumolysin, autolysin, or surface proteins PspA and PsaA. Isogenic
      pavA mutants of encapsulated S. pneumoniae D39 were approximately 104-fold
      attenuated in virulence in the mouse sepsis model. These results provide evidence
      that PavA fibronectin-binding protein plays a direct role in the pathogenesis of
      pneumococcal infections.

PMID- 11580844
TI  - Quantitative analysis of expression of two circadian clock-controlled gene
      clusters coding for the bidirectional hydrogenase in the cyanobacterium
      Synechococcus sp. PCC7942.
AB  - Hydrogen metabolism is of central interest in cyanobacterial research because of
      its potential applications. The gene expression and physiological role of the
      cyanobacterial bidirectional NAD(P)+-reducing hydrogenase are poorly understood.
      Transcription rates of hoxEF and hoxUYH encoding this enzyme have been studied in
      Synechococcus sp. PCC7942. PhoxU activity was about three times higher than that
      of PhoxE. Circadian phasing of both promoters was found to be synchronous and
      influenced expression levels by at least one order of magnitude. This is the
      first demonstration of circadian control of gene expression for any hydrogenase.
      For the majority of PhoxU-driven messages, transcription presumably terminates
      between hoxU and hoxH. Being part of a polycistronic hoxUYHW... operon, hoxW,
      encoding a protease involved in C-terminal processing of the hydrogenase large
      subunit HoxH, is mainly expressed by its own promoter, PhoxW. The complex
      transcript formation may be a key feature for controlling bidirectional
      hydrogenase expression in vivo.

PMID- 11580845
TI  - FimH-mediated autoaggregation of Escherichia coli.
AB  - Autoaggregation is a phenomenon thought to contribute to colonization of
      mammalian hosts by pathogenic bacteria. Type 1 fimbriae are surface organelles of
      Escherichia coli that mediate d-mannose-sensitive binding to various host
      surfaces. This binding is conferred by the minor fimbrial component FimH. In this
      study, we have used random mutagenesis to identify variants of the FimH adhesin
      that confer the ability of E. coli to autoaggregate and settle from liquid
      cultures. Three separate autoaggregating clones were identified, all of which
      contained multiple amino acid changes located within the N-terminal receptor
      binding domain of FimH. Autoaggregation could not be inhibited by mannose, but
      was inhibited by growth at temperatures at or below 30 degrees C. Using green
      fluorescent protein (GFP) as a reporter, we show that the autoaggregating clones
      do not mix with wild-type fimbriated cells. Electron microscopy shows that
      autoaggregating cells produce fimbriae with a twisted and entangled appearance.
      We present evidence that autoaggregating versions of FimH also occur in nature.
      Our results stress the highly adaptive nature of the ubiquitous FimH adhesin.

PMID- 11580846
TI  - The KEX2 gene of Candida glabrata is required for cell surface integrity.
AB  - Candida glabrata has emerged as one of the most common causes of candidosis. In
      order to identify factors that are necessary for viability and pathogenicity of
      this fungal pathogen, we analysed the role of the KEX2 gene, which codes for a
      regulatory endoproteinase that is known to process certain virulence factors in
      Candida albicans. The KEX2 gene from C. glabrata was cloned and found to have 51%
      and 62% identity and high structural similarities to the homologous counterparts
      in C. albicans and Saccharomyces cerevisiae. KEX2 was expressed at all time
      points investigated during growth in complex medium. In order to investigate the
      role of this putative regulatory proteinase, Kex2-deficient mutants were
      produced. In addition to known kex2 phenotypes, such as pH and calcium
      hypersensitivity, the mutants grew in cellular aggregates and were found to be
      hypersensitive to several antifungal drugs that target the cell membrane,
      including azoles, amorolfine and amphotericin B. Ultrastructural investigation
      after exposure to low doses of itraconazole showed azole-specific alterations
      such as enlarged vacuoles and proliferation of the cytoplasmatic membrane in the
      kex2 mutants, but not in the control strains. In contrast, antifungals such as 5
      flucytosine and hydroxypyridones inhibited growth of the kex2 mutants and the
      control strains to the same extent. In an in vitro model of oral candidosis, kex2
      mutants showed reduced tissue damage in the presence of itraconazole compared
      with the control infections. These data suggest that Kex2 is involved in the
      processing of proteins that are essential for cell surface integrity of C.
      glabrata.

PMID- 11580847
TI  - Enterohaemorrhagic and enteropathogenic Escherichia coli use a different Tir
      based mechanism for pedestal formation.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) adheres to the host intestinal
      epithelium, resulting in the formation of actin pedestals beneath adhering
      bacteria. EHEC and a related pathogen, enteropathogenic E. coli (EPEC), insert a
      bacterial receptor, Tir, into the host plasma membrane, which is required for
      pedestal formation. An important difference between EPEC and EHEC Tir is that
      EPEC but not EHEC Tir is tyrosine phosphorylated once delivered into the host. In
      this study, we assessed the role of Tir tyrosine phosphorylation in pedestal
      formation by EPEC and EHEC. In EPEC, pedestal formation is absolutely dependent
      on Tir tyrosine phosphorylation and is not complemented by EHEC Tir. The protein
      sequence surrounding EPEC Tir tyrosine 474 is critical for Tir tyrosine
      phosphorylation and pedestal formation by EPEC. In contrast, Tir tyrosine
      phosphorylation is not required for pedestal formation by EHEC. EHEC forms
      pedestals with both wild-type EPEC Tir and the non-tyrosine-phosphorylatable EPEC
      Tir Y474F. Pedestal formation by EHEC requires the type III delivery of
      additional EHEC factors into the host cell. These findings highlight differences
      in the mechanisms of pedestal formation by these closely related pathogens and
      indicate that EPEC and EHEC modulate different signalling pathways to affect the
      host actin cytoskeleton.

PMID- 11580848
TI  - Xis protein of the conjugative transposon Tn916 plays dual opposing roles in
      transposon excision.
AB  - The binding of Tn916 Xis protein to its specific sites at the left and right ends
      of the transposon was compared using gel mobility shift assays. Xis formed two
      complexes with different electrophoretic mobilities with both right and left
      transposon ends. Complex II, with a reduced mobility, formed at higher
      concentrations of Xis and appeared at an eightfold lower Xis concentration with a
      DNA fragment from the left end of the transposon rather than with a DNA fragment
      from the right end of the transposon, indicating that Xis has a higher affinity
      for the left end of the transposon. Methylation interference was used to identify
      two G residues that were essential for binding of Xis to the right end of Tn916.
      Mutations in these residues reduced binding of Xis. In an in vivo assay, these
      mutations increased the frequency of excision of a minitransposon from a plasmid,
      indicating that binding of Xis at the right end of Tn916 inhibits transposon
      excision. A similar mutation in the specific binding site for Xis at the left end
      of the transposon did not reduce the affinity of Xis for the site but did perturb
      binding sufficiently to alter the pattern of protection by Xis from nuclease
      cleavage. This mutation reduced the level of transposon excision, indicating that
      binding of Xis to the left end of Tn916 is required for transposon excision.
      Thus, Xis is required for transposon excision and, at elevated concentrations,
      can also regulate this process.

PMID- 11580849
TI  - HLA-DR and -DQ polymorphism in Cameroon.
AB  - HLA-DRB1, -DQA1 and -DQB1 allele frequencies were determined by high-resolution
      polymerase chain reaction using sequence-specific oligonucleotide probes (PCR
      SSOP) and/or DNA sequencing in 126 healthy individuals in Cameroon. Eighteen
      DRB1, 11 DQA1, and 18 DQB1 alleles were observed. The most common alleles at each
      locus were DRB1*1503 (29%), DRB1*1301 (13%); DQA1*0102 (38%), DQA1*0302 (11%),
      DQA1*0401 (11%); and DQB1*0602 (31%), DQB1*0301 (13%), DQB1*0501 (12%). Forty
      four different haplotypes were identified including 12 novel haplotypes
      demonstrating the HLA class II diversity resulting from allele combinations in
      this population. A single predominant DRB1*1503-DQA1*0102-DQB1*0602 haplotype was
      observed with a frequency of 27%. In summary, this study of HLA class II
      polymorphism in Cameroon demonstrates the extent of diversity in this population.

PMID- 11580850
TI  - Diversity of HLA among Taiwan's indigenous tribes and the Ivatans in the
      Philippines.
AB  - Taiwan's indigenous tribes, especially the east coast tribes are not only closely
      related to Oceania but also with the Australian aborigines. The Ivatans of the
      Batan Islands in the Philippines are closely related to the Yami tribe of Taiwan
      as cultural and anthropological studies have shown. Many DRB1 alleles (*15021,
      *16021, *0404, *04051, *11011, *12021, *1401, *08032) have high allele
      frequencies (>20%) in certain tribes, suggesting Taiwan's indigenous tribes are
      homogeneous populations. These high frequency DRB1 alleles and also some HLA-A-B
      DR haplotypes found in Taiwan's indigenous tribes are also found in Oceania,
      Australian aborigines, south and north east Asians and American Indians, lending
      further support to our previous findings that Taiwan's indigenous tribes are more
      or less genetically related to both northern and southern Asians, possibly as
      well as Amerindians. HLA-A*2402 with a remarkably high frequency among Taiwan's
      indigenous tribes (52.1% approximately 86.3%), especially the central mountain
      tribes, possibly represents not only founder effects and population bottlenecks,
      but also positive selection of the allele. Although the Ami tribe has the highest
      ever reported frequencies of the DRB1*0404 and DRB1*0405, these alleles have not
      been found to be associated with rheumatoid arthritis as previously described for
      Caucasians. In addition, DRB1*1401 has a high frequency in most tribes but is not
      associated with psoriasis as previously indicated in some studies, suggesting the
      involvement of some additional genetic and/or environmental factors mechanism in
      the development of these diseases.

PMID- 11580851
TI  - CD1 genotyping of patients with Mycobacterium malmoense pulmonary disease.
AB  - Mycobacterium malmoense is an opportunistic mycobacterium that occasionally
      causes disease in non-immunosuppressed individuals. As only a few individuals
      exposed to these organisms actually develop clinical disease, it is possible
      there is a genetic component to susceptibility. CD1 molecules are capable of
      presenting antigens from more virulent mycobacteria to T cells; therefore, we
      were interested in discovering whether recently described polymorphisms in CD1
      molecules modulated susceptibility to M. malmoense pulmonary disease. The CD1
      system comprises five genes (CD1A, -B, -C, -D, and -E) located on chromosome 1
      (1q22-23). CD1 molecules are structurally and functionally related to major
      histocompatibility complex (MHC) class I molecules and are expressed on dedicated
      antigen-presenting cells. The primary function of CD1 molecules is to present
      lipid and glycolipid antigens to T cells. We have developed an allele-specific
      polymerase chain reaction-sequence-specific primer (PCR-SSP) method of CD1
      genotyping. Using this method, we compared the allele and haplotype frequencies
      of CD1 in 49 HIV-negative patients with M. malmoense pulmonary disease with those
      in 342 normal controls. The CD1A and CD1E alleles were nominally identified as
      CD1A*01, CD1A*02, CD1E*01 and CD1E*02, and the control gene frequencies were
      found to be 5%, 95%, 67% and 33%, respectively. No significant difference was
      observed between the patient and control cohorts. Positive linkage disequilibrium
      values of 0.73 were observed between CD1A*02 and CD1E*01 (P<0.0001; chi2 test),
      and 0.94 between CD1A*01 and CD1E*02 (P<0.0001; chi2 test). Typing was also
      performed for two previously described CD1D alleles (CD1D*01 and CD1D*02),
      although only CD1D*01 was detected.

PMID- 11580852
TI  - Polymorphism of the human retinoid X receptor beta and linkage disequilibrium
      with HLA-DPB1.
AB  - The human retinoid X receptor beta (RXRB) gene is localized in the major
      histocompatibility complex (MHC) region between DPB1 and RING2. The RXRB gene
      sequence reported by different investigators suggests that the gene may be
      polymorphic. In this study, we confirmed one polymorphism by sequencing genomic
      DNA from four Caucasian individuals. We also developed a restriction fragment
      length polymorphism (RFLP) analysis to detect this specific polymorphism. Linkage
      analysis studies between RXRB alleles and a number of HLA markers showed
      significant linkage disequilibrium between RXRB*T and HLA-DPB1*0401.

PMID- 11580853
TI  - A new HLA-B*27 allele (B*2719) identified in a Lebanese patient affected with
      ankylosing spondylitis.
AB  - Eighteen different HLA-B*27 alleles (B*2701-B2718) have so far been recognized by
      the WHO Nomenclature Committee for Factors of the HLA System. Frequency and
      disease association of these alleles with spondyloarthropathies differ among
      ethnic groups. We describe here a novel HLA-B*27 subtype identified in a Lebanese
      patient suffering from ankylosing spondylitis (AS). This new variant differs from
      the common HLA-B*2705 DNA sequence at five different nucleotide positions. These
      nucleotide changes lead to three amino acid differences in the alpha2 domain; Thr
      to Ile at position 94, Leu to Ile at position 95 and Asn to Arg at position 97.
      Since this novel allele is encountered in an AS patient, the associated sequence
      changes are not expected to affect significantly neither the presentation of a
      putative arthritogenic peptide nor the conformation-dependent recognition by
      effector cells.

PMID- 11580854
TI  - Sequencing based typing for HLA-C. Identification of three new alleles: Cw*0307,
      Cw*0502 and Cw*0504.
AB  - HLA-C has been described as a transplantation locus in the unrelated bone marrow
      transplantation setting, and noticeably the number of mismatches between HLA-A,
      B,-DRB1 compatible pairs is considerably high. Sequencing based typing (SBT) is
      an accurate and efficient methodology utilised in the HLA class I and II allele
      level of resolution. SBT for HLA-C locus was applied on a sample of 40 HLA
      A,B,DRB1,DRB3/4/5,DQB1-compatible bone marrow recipient-donor pairs, and 3 new
      HLA-C alleles have been found. Cw*0307, well defined by serology as Cw3, showed
      two amino acid changes at the NK motif 77-80 regarding all described Cw*03
      alleles, N77K80 instead of S77N80. Two new Cw*05 alleles were described, Cw*0502
      properly typed by serology, and Cw*0504 that behaves as a short antigen. Cw*0502
      differed from Cw*0501 by only one nucleotide at exon 3, that generated an amino
      acid replacement at codon 177, K to E. Cw*0504 differs from Cw*0501 by two
      clustered amino acid positions (114 and 116) placed at the peptide binding site.
      The rate of new HLA-C alleles found in this small series evidences a high grade
      of hidden HLA-C diversity in the Spanish population, particularly in the well
      defined serologic specificities.

PMID- 11580855
TI  - Three newly identified HLA-B alleles: B*5124, B*5306, B*5307 and confirmation of
      B*0809 and B*5606.
AB  - Five HLA-B sequences are described which have been detected as irregular patterns
      during routine molecular typing. Sequencing of HLA-B exon 2 and 3, both
      heterozygous and after group specific amplification, revealed three new HLA-B
      alleles: B*5124, B*5306 and B*5307, whereas the sequences of B*0809 and B*5606
      were confirmed. Serological typing showed that B*0809 is expressed as a regular
      B8, B*5124 as a regular B51, B*5306 as a B51/B53-like variant and B*5606 as a
      B"blank"-Bw6.

PMID- 11580856
TI  - Identification of two new HLA-B22 variants, HLA-B*5509 and B*5606.
AB  - In our recent study using high-resolution HLA-B locus typing by sequence-based
      typing (SBT) we identified 9 new alleles in a total of 355 unrelated individuals
      (4). Three of them concerned an allele belonging to the B22 group. One of them,
      B*5607, showed the unusual presence of a Bw4 sequence motif, as described
      previously (5). In this report the other two B22 variants are described; one
      belonging to the B55 specificity and named B*5509; the other one being a B*56
      allele and assigned B*5606, which brings the total number of alleles belonging to
      the B22 group to 18.

PMID- 11580857
TI  - Identification of the novel allele HLA-DRB1*1137 which probably originated from
      DRB1*11011: implications for mismatch with its ancestor allele at bone marrow
      transplantation.
AB  - The identification of the new allele HLA-DRB1*1137, which was found in a
      Caucasian individual, is described. In the sequence analysis the new allele
      differs from DRB1*11011 by position 227 (T>A) which is located in exon 2. At the
      protein level, the new allele has one amino acid difference compared to DRB1*1101
      (Phe47Tyr). Residue 47 is likely to contribute to the peptide binding site of HLA
      DR11 and thus to be important for peptide binding. However, as phenylalanine and
      tyrosine have very similar physical and chemical features allogenicity in case of
      mismatch at bone marrow transplantation may be weak.

PMID- 11580858
TI  - Polymorphism in codon 17 of the CTLA-4 gene (+49 A/G) is not associated with
      susceptibility to rheumatoid arthritis in British Caucasians.
AB  - The role of the CTLA-4 antigen in the development of autoimmune diseases is well
      documented, with several autoimmune disorders showing association or linkage with
      the CTLA-4 locus. Its role in the aetiology of rheumatoid arthritis (RA) however,
      remains unclear, as the functional studies of the B7-CTLA-4 pathway in mouse
      models of RA and genetic studies in humans have given contrasting results. We
      have studied the single nucleotide polymorphism at position +49 (A/G) of the CTLA
      4 gene, in a cohort of 421 RA cases and 452 healthy controls from the UK. Despite
      the high statistical power to detect even a weak susceptibility effect, no
      significant association was found. We also analysed the distribution of the
      allele and genotype frequencies with respect to the presence of the shared
      epitope (a known RA susceptibility factor) and found no statistically significant
      differences. We conclude that, although the importance of the B7-CTLA-4
      interaction in the development of RA can not be excluded, the CTLA-4 gene is
      unlikely to be a predisposing factor to this disease.

PMID- 11580859
TI  - Nomenclature for factors of the dog major histocompatibility system (DLA), 2000:
      Second report of the ISAG DLA Nomenclature Committee.
AB  - The ISAG DLA Nomenclature Committee met during the "Comparative Evolution of the
      Mammalian MHC" meeting in Manchester, England on 10th September 2000. The main
      points discussed were the naming of class I genes and alleles, and the inclusion
      of alleles from other canidae.

PMID- 11580860
TI  - A genomic timescale for the origin of eukaryotes.
AB  - BACKGROUND: Genomic sequence analyses have shown that horizontal gene transfer
      occurred during the origin of eukaryotes as a consequence of symbiosis. However,
      details of the timing and number of symbiotic events are unclear. A timescale for
      the early evolution of eukaryotes would help to better understand the
      relationship between these biological events and changes in Earth's environment,
      such as the rise in oxygen. We used refined methods of sequence alignment, site
      selection, and time estimation to address these questions with protein sequences
      from complete genomes of prokaryotes and eukaryotes. RESULTS: Eukaryotes were
      found to evolve faster than prokaryotes, with those eukaryotes derived from
      eubacteria evolving faster than those derived from archaebacteria. We found an
      early time of divergence (approximately 4 billion years ago, Ga) for
      archaebacteria and the archaebacterial genes in eukaryotes. Our analyses support
      at least two horizontal gene transfer events in the origin of eukaryotes, at 2.7
      Ga and 1.8 Ga. Time estimates for the origin of cyanobacteria (2.6 Ga) and the
      divergence of an early-branching eukaryote that lacks mitochondria (Giardia) (2.2
      Ga) fall between those two events. CONCLUSIONS: We find support for two symbiotic
      events in the origin of eukaryotes: one premitochondrial and a later
      mitochondrial event. The appearance of cyanobacteria immediately prior to the
      earliest undisputed evidence for the presence of oxygen (2.4-2.2 Ga) suggests
      that the innovation of oxygenic photosynthesis had a relatively rapid impact on
      the environment as it set the stage for further evolution of the eukaryotic cell.

PMID- 11580861
TI  - Improvements to parallel plate flow chambers to reduce reagent and cellular
      requirements.
AB  - BACKGROUND: The parallel plate flow chamber has become a mainstay for examination
      of leukocytes under physiologic flow conditions. Several design modifications
      have occurred over the years, yet a comparison of these different designs has not
      been performed. In addition, the reagent requirements of many designs prohibit
      the study of rare leukocyte populations and require large amounts of reagents.
      RESULTS: In this study, we evaluate modifications to a newer parallel plate flow
      chamber design in comparison to the original parallel plate flow chamber
      described by Lawrence et al. We show that modifications in the chamber size,
      internal tubing diameters, injection valves, and a recirculation design may
      dramatically reduce the cellular and reagent requirements without altering
      measurements. CONCLUSIONS: These modifications are simple and easily implemented
      so that study of rare leukocyte subsets using scarce or expensive reagents can
      occur.

PMID- 11580862
TI  - Development of Dengue virus type 2 replicons capable of prolonged expression in
      host cells.
AB  - BACKGROUND: As part of a program to develop a Dengue virus vaccine which avoids
      the deleterious effects of antibody dependent enhancement (ADE) of infection
      mediated by antibodies to Dengue virus structural proteins, we have begun to
      investigate the possibility of designing Dengue vaccines based on non-structural
      proteins. RESULTS: Dengue constructs which lack major structural proteins
      replicate intracellularly in tissue culture. These replicons are capable of
      prolonged expression of Dengue virus non-structural proteins for at least seven
      days in culture. CONCLUSIONS: Dengue virus genomes lacking major structural
      proteins can, like other flaviviruses, replicate intracellularly and express
      virus non-structural proteins with minimal toxicity to host cells. These findings
      pave the way for the development of dengue virus replicons as a form of live,
      attenuated virus vaccine.

PMID- 11580863
TI  - Transcriptional transactivation by selected short random peptides attached to
      lexA-GFP fusion proteins.
AB  - BACKGROUND: Transcriptional transactivation is a process with remarkable
      tolerance for sequence diversity and structural geometry. In studies of the
      features that constitute transactivating functions, acidity has remained one of
      the most common characteristics observed among native activation domains and
      activator peptides. RESULTS: We performed a deliberate search of random peptide
      libraries for peptides capable of conferring transcriptional transactivation on
      the lexA DNA binding domain. Two libraries, one composed of C-terminal fusions,
      the other of peptide insertions within the green fluorescent protein structure,
      were used. We show that (i) peptide sequences other than C-terminal fusions can
      confer transactivation; (ii) though acidic activator peptides are more common,
      charge neutral and basic peptides can function as activators; and (iii) peptides
      as short as 11 amino acids behave in a modular fashion. CONCLUSIONS: These
      results support the recruitment model of transcriptional activation and, combined
      with other studies, suggest the possibility of using activator peptides in a
      variety of applications, including drug development work.

PMID- 11580865
TI  - Assessing the heritability of attentional networks.
AB  - BACKGROUND: Current efforts to study the genetics of higher functions have been
      lacking appropriate phenotypes to describe cognition. One of the problems is that
      many cognitive concepts for which there is a single word (e.g. attention) have
      been shown to be related to several anatomical networks. Recently we have
      developed an Attention Network Test (ANT) that provides a separate measure for
      each of three anatomically defined attention networks. In this small scale study,
      we ran 26 pairs of MZ and DZ twins in an effort to determine if any of these
      networks show sufficient evidence of heritability to warrant further exploration
      of their genetic basis. RESULTS: The efficiency of the executive attention
      network, that mediates stimulus and response conflict, shows sufficient
      heritability to warrant further study. Alerting and overall reaction time show
      some evidence for heritability and in our study the orienting network shows no
      evidence of heritability. CONCLUSIONS: These results suggest that genetic
      variation contributes to normal individual differences in higher order executive
      attention involving dopamine rich frontal areas including the anterior cingulate.
      At least the executive portion of the ANT may serve as a valid endophenotype for
      larger twin studies and subsequent molecular genetic analysis in normal subject
      populations.

PMID- 11580864
TI  - Bone morphogenetic protein-5 (BMP-5) promotes dendritic growth in cultured
      sympathetic neurons.
AB  - BACKGROUND: BMP-5 is expressed in the nervous system throughout development and
      into adulthood. However its effects on neural tissues are not well defined. BMP-5
      is a member of the 60A subgroup of BMPs, other members of which have been shown
      to stimulate dendritic growth in central and peripheral neurons. We therefore
      examined the possibility that BMP-5 similarly enhances dendritic growth in
      cultured sympathetic neurons. RESULTS: Sympathetic neurons cultured in the
      absence of serum or glial cells do not form dendrites; however, addition of BMP-5
      causes these neurons to extend multiple dendritic processes, which is preceded by
      an increase in phosphorylation of the Smad-1 transcription factor. The dendrite
      promoting activity of BMP-5 is significantly inhibited by the BMP antagonists
      noggin and follistatin and by a BMPR-IA-Fc chimeric protein. RT-PCR and
      immunocytochemical analyses indicate that BMP-5 mRNA and protein are expressed in
      the superior cervical ganglia (SCG) during times of initial growth and rapid
      expansion of the dendritic arbor. CONCLUSIONS: These data suggest a role for BMP
      5 in regulating dendritic growth in sympathetic neurons. The signaling pathway
      that mediates the dendrite-promoting activity of BMP-5 may involve binding to
      BMPR-IA and activation of Smad-1, and relative levels of BMP antagonists such as
      noggin and follistatin may modulate BMP-5 signaling. Since BMP-5 is expressed at
      relatively high levels not only in the developing but also the adult nervous
      system, these findings suggest the possibility that BMP-5 regulates dendritic
      morphology not only in the developing, but also the adult nervous system.

PMID- 11580866
TI  - Effects of two atypical neuroleptics, olanzapine and risperidone, on the function
      of the urinary bladder and the external urethral sphincter in anesthetized rats.
AB  - BACKGROUND: A previous report showed that the atypical neuroleptic clozapine
      resulted in marked changes in urodynamic parameters and greatly inhibited the
      activity of the external urethral sphincter in anesthetized rats. Such findings
      may help explain the high incidence of urinary disturbances reported during
      clozapine therapy. In an effort to extend our observations to other atypical
      neuroleptic agents, the present study investigated the effects of two newer
      atypical antipsychotics, olanzapine and risperidone, on the bladder and external
      urethral sphincter during cystometry in anesthetized rats. RESULTS: At a dose of
      0.1 mg/kg (i.v.), olanzapine decreased the micturition volume and increased the
      residual volume. In addition, olanzapine decreased the expulsion time and the
      amplitude of the high frequency oscillations observed during the expulsion phase.
      Larger doses (1 mg/kg) had a greater effect. Olanzapine also reduced the activity
      recorded from the external urethral sphincter, and the bursting observed during
      the expulsion phase was abolished by 1.0 mg/kg. Risperidone had similar effects
      although the maximal effects were smaller than those observed with olanzapine.
      The amplitude of bladder contractions elicited by electrical stimulation of the
      pelvic nerve was reduced by olanzapine but not risperidone suggesting a possible
      anti-muscarinic peripheral effect of olanzapine. CONCLUSIONS: Olanzapine and
      risperidone significantly altered several voiding parameters and decreased the
      activity of the external urethral sphincter in the anesthetized rat. We propose
      that these effects are due to the central action of these drugs and not to
      peripheral effects. These findings may explain some of the clinical reports of
      urinary incontinence with risperidone and may predict similar occurrences with
      olanzapine therapy.

PMID- 11580867
TI  - S-carboxymethylcysteine in the treatment of glue ear: quantitative systematic
      review.
AB  - OBJECTIVE: To establish the clinical relevance of S-carboxymethylcysteine in the
      treatment of glue ear in children using measures approximating those saving a
      child from operation for grommet insertion. DATA SOURCES: Cochrane Library,
      MEDLINE, EMBASE, PubMed, reference lists and reviews were used for randomised
      controlled trials comparing S-carboxymethylcysteine with placebo. Seven trials
      involving 283 children and 146 ears were found. REVIEW METHODS: Studies were
      randomised, double-blind comparisons of S-carboxymethylcysteine (any dose and
      duration) with placebo in otitis media with effusion. Quality of trial reporting
      and validity of methods were assessed and used in sensitivity analysis. Main
      outcomes were relative benefit and number-needed-to-treat to prevent one grommet
      operation compared with placebo. RESULTS: Successful outcomes were obtained in
      17% of children given placebo (range 5% to 38% in individual studies) and in 35%
      of children given S-carboxymethylcysteine (range 22 to 80%). For combined data
      (children and ears) the relative benefit was 2.0 (95%CI 1.4 to 2.8) and number
      needed-to-treat 5.5 (95% confidence interval 3.8 to 9.8). Pooled data from trials
      of higher reporting quality (4/7) or methodological validity (3/7) tended to have
      lower efficacy but were not statistically different from those of lower quality
      or validity. CONCLUSION: S-carboxymethylcysteine is effective in the treatment of
      children with glue ear. For every five or six children treated with S
      carboxymethylcysteine over one to three months, one will not undergo surgery for
      grommet insertion who would have done had they been given placebo. The confidence
      in this conclusion is limited because studies included relatively few children.

PMID- 11580868
TI  - Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of
      children with hydrocephalus.
AB  - BACKGROUND: Elevated intracranial pressure (ICP) resulting from impaired drainage
      of cerebrospinal fluid (CSF) causes hydrocephalus with damage to the central
      nervous system. Clinical symptoms of elevated intracranial pressure (ICP) in
      infants may be difficult to diagnose, leading to delayed treatment by shunt
      placement. Until now, no biochemical marker of elevated ICP has been available
      for clinical diagnosis and monitoring. In experimental animal models, nerve
      growth factor (NGF) and neurotrophin-3 (NT-3) have been shown to be produced by
      glial cells as an adaptive response to hypoxia. We investigated whether
      concentrations of NGF and NT-3 are increased in the CSF of children with
      hydrocephalus. METHODS: NGF was determined in CSF samples collected from 42
      hydrocephalic children on 65 occasions (taps or shunt placement surgery). CSF
      samples obtained by lumbar puncture from 22 children with suspected, but
      unconfirmed bacterial infection served as controls. Analysis was performed using
      ELISA techniques. RESULTS: NGF concentrations in hydrocephalic children were over
      50-fold increased compared to controls (median 225 vs 4 pg/mL, p < 0.0001). NT-3
      was detectable (> 1 pg/mL) in 14/31 hydrocephalus samples at 2-51 pg/mL but in
      none of 11 control samples (p = 0.007). CONCLUSION: NGF and NT-3 concentrations
      are increased in children with hydrocephalus. This may represent an adaptive
      response of the brain to elevated ICP.

PMID- 11580869
TI  - A prospective study of rural drinking water quality and acute gastrointestinal
      illness.
AB  - BACKGROUND: This study examined the relationship between the bacteriological
      contamination of drinking water from private wells and acute gastrointestinal
      illness (AGII), using current government standards for safe drinking water.
      METHODS: A prospective cohort study was conducted using 235 households (647
      individuals) randomly selected from four rural hamlets. Data were collected by
      means of a self-administered questionnaire, a self-report diary of symptoms and
      two drinking water samples. RESULTS: Twenty percent of households sampled, had
      indicator bacteria (total coliform or Escherichia coli (E. coli)) above the
      current Canadian and United States standards for safe drinking water. No
      statistically significant associations between indicator bacteria and AGII were
      observed. The odds ratio (OR) for individuals exposed to E. coli above the
      current standards was 1.52 (95% confidence interval (CI), 0.33-6.92), compared to
      individuals with levels below current standards. The odds ratio estimate for
      individuals exposed to total coliforms above the current standards was 0.39 (95%
      CI, 0.10-1.50). CONCLUSIONS: This study observed a high prevalence of
      bacteriological contamination of private wells in the rural hamlets studied.
      Individual exposure to contaminated water defined by current standards may be
      associated with an increased risk of AGII.

PMID- 11580870
TI  - Laparoscopic and open surgery for pheochromocytoma.
AB  - BACKGROUND: Laparoscopic adrenalectomy is a promising alternative to open surgery
      although concerns exist in regard to laparoscopic treatment of pheocromocytoma.
      This report compares the outcome of laparoscopic and conventional (open)
      resection for pheocromocytoma particular in regard to intraoperative hemodynamic
      stability and postoperative patient comfort. METHODS: Seven patients
      laparoscopically treated (1997-2000) and nine patients treated by open resection
      (1990-1996) at the National Hospital (Rikshospitalet), Oslo. Peroperative
      hemodynamic stability including need of vasoactive drugs was studied.
      Postoperative analgesic medication, complications and hospital stay were
      recorded. RESULTS: No laparoscopic resections were converted to open procedure.
      Patients laparoscopically treated had fewer hypertensive episodes (median 1 vs.
      2) and less need of vasoactive drugs peroperatively than patients conventionally
      operated. There was no difference in operative time between the two groups
      (median 110 min vs. 125 min for adrenal pheochromocytoma and 235 vs. 210 min for
      paraganglioma). Postoperative need of analgesic medication (1 vs. 9 patients) and
      hospital stay (median 3 vs. 6 days) were significantly reduced in patients
      laparoscopically operated compared to patients treated by the open technique.
      CONCLUSION: Surgery for pheochromocytoma can be performed laparoscopically with a
      safety comparable to open resection. However, improved hemodynamic stability
      peroperatively and less need of postoperative analgesics favour the laparoscopic
      approach. In experienced hands the laparoscopic technique is concluded to be the
      method of choice also for pheocromocytoma.

PMID- 11580871
TI  - Transcutaneous flow related variables measured in vivo: the effects of gender.
AB  - BACKGROUND: The identification of potential sources of error is a crucial step
      for any new assessment technique. This is the case for transcutaneous variables,
      such as flow and arterial gases, which have been applied as functional indicators
      of various aspects of human health. Regarding gender, a particular subject
      related determinant, it is often claimed that women present higher transcutaneous
      oxygen pressure (tcpO2) values than men. However, the statistical significance of
      this finding is still uncertain. METHODS: The haemodynamical-vascular response to
      a local reactive hyperaemia procedure (the tourniquet cuff manoeuvre) was studied
      in two previously selected group of volunteers (n = 16; 8 women and 8 men). The
      effect of gender was assessed under standardised experimental conditions, using
      the transcutaneous flow-related variables tcpO2-tcpCO2 and Laser-doppler
      Flowmetry (LDF). RESULTS: Regarding tcpO2, statistically significant differences
      between genders were not found, although higher values were consistently found
      for the gases in the female group. Regarding LDF, high statistically significant
      differences (p < 0.005) were found, with the men's group presenting the highest
      values and variability. Other derived parameters used to characterise the
      vascular response following the cuff-deflation (t-peak) were similar in both
      groups. CONCLUSIONS: The relative influence of gender was not clearly
      demonstrated using these experimental conditions. However the gender-related LDF
      differences suggest that further investigation should be done on this issue.
      Perhaps in the presence of certain pathological disparities involving peripheral
      vascular regulation, other relationships may be found between these variables.

PMID- 11580872
TI  - The inflammatory infiltrate in the acute stage of the dextran sulphate sodium
      induced colitis: B cell response differs depending on the percentage of DSS used
      to induce it.
AB  - BACKGROUND: Experimental colitis with features similar to inflammatory bowel
      disease (IBD) has initially been described. A detailed analysis of inflammatory
      cells has not yet been described. Therefore in this study we characterized the
      cells involved in the acute phase of the colitis and compared those findings to
      what is known about human IBD. METHODS: Colitis was induced in BALB/C and C57Bl6
      mice by ingestion of 2.5% and 5% DSS in the drinking water for 8 days. Cells were
      labelled by immunohistochemical staining with F4/80 and ER-MP20 for macrophages,
      TIB 120 for MHC Class II presentation, and anti-CD4 and anti-CD8 antibodies. They
      were enumerated by using a novel method that employs video image analysis.
      Immunoglobulin-producing cells were enumerated by immunofluorescent staining for
      IgA, IgG and IgM and counting by using confocal microscopy. RESULTS: Inflammatory
      infiltrate in the acute phase of the dextran sulphate sodium (DSS) -induced
      colitis consists predominantly of macrophages, neutrophils and eosinophils.
      Neutrophils increase in numbers and crypt abscesses were also seen. Increased
      macrophage numbers were due to recently recruited monocytes from the peripheral
      circulation. It does not appear that there are any changes in T cell numbers or
      distribution. The inflammation induced changes in immunoglobulin-producing cells
      with IgA-producing cells affected the most. CONCLUSIONS: The effect on Ig
      producing cells depends on the percentage of DSS used to induce colitis. In
      general, 2.5% DSS induces an increase and 5% DSS a depletion of these cells.

PMID- 11580873
TI  - A population based time series analysis of asthma hospitalisations in Ontario,
      Canada: 1988 to 2000.
AB  - BACKGROUND: Asthma is a common yet incompletely understood health problem
      associated with a high morbidity burden. A wide variety of seasonally variable
      environmental stimuli such as viruses and air pollution are believed to influence
      asthma morbidity. This study set out to examine the seasonal patterns of asthma
      hospitalisations in relation to age and gender for the province of Ontario over a
      period of 12 years. METHODS: A retrospective, population-based study design was
      used to assess temporal patterns in hospitalisations for asthma from April 1,
      1988 to March 31, 2000. Approximately 14 million residents of Ontario eligible
      for universal healthcare coverage during this time were included for analysis.
      Time series analyses were conducted on monthly aggregations of hospitalisations.
      RESULTS: There is strong evidence of an autumn peak and summer trough seasonal
      pattern occurring every year over the 12-year period (Fisher-Kappa (FK) = 23.93,
      p > 0.01; Bartlett Kolmogorov Smirnov (BKS) = 0.459, p < 0.01). This pattern was
      observed in both sexes. However, young males (0-4 years) were hospitalised at two
      to three times the rate of females of the same age. Rates were much lower in the
      older age groups. A downward trend in asthma hospitalisations was observed in the
      total population over the twelve-year period (beta = -0.980, p < 0.01).
      CONCLUSIONS: A clear and consistent seasonal pattern was observed in this study
      for asthma hospitalisations. These findings have important implications for the
      development of effective management and prevention strategies.

PMID- 11580875
TI  - Guest editors' introduction: special issue on sensor evolution.

PMID- 11580874
TI  - Impact of patient characteristics on the risk of influenza/ILI-related
      complications.
AB  - BACKGROUND: We sought to quantify the impact of patient characteristics on
      complications and health care costs associated with influenza and influenza-like
      illness (ILI) in a nonelderly population. METHODS: Patients with medical
      reimbursement claims for influenza in the 1996-1997 season were identified from
      the automated database of a large private New England Insurer (NEI). Influenza
      care during the 21- day follow-up period was characterized according to age,
      gender, vaccine status, co-morbidities, prior influenza/ILI episodes, treatments,
      and recent health care costs and related diagnoses. RESULTS: There were 6,241
      patients. Approximately 20% had preexisting chronic lung disease. Overall, 23%
      had health care services for possible complications, among which respiratory
      diagnoses were the most common (13%). Two percent of the influenza/ILI episodes
      involved hospitalization, with a median stay of five days. Factors most strongly
      predictive of hospitalizations and complications were preexisting malignancy
      (hospitalizations OR = 3.7 and complications OR = 2.4), chronic heart disease (OR
      = 3.2 and OR = 1.8), diabetes (OR = 2.2 and OR = 1.7) and recent illnesses that
      would have counted as complications had they occurred during an influenza/ILI
      episode (hospitalizations OR = 3.2 and complications OR = 1.5). The same factors
      affected influenza-related costs and total costs of care as dramatically as they
      affected complication rates. CONCLUSIONS: Influenza/ILI-related costs are driven
      by the characteristics that predict complications of influenza. Patients with
      chronic illness and those with recent acute respiratory events are the most
      likely to experience complications and hospitalizations.

PMID- 11580876
TI  - A study of the simulated evolution of the spectral sensitivity of visual agent
      receptors.
AB  - In this article we study a model for the evolution of the spectral sensitivity of
      visual receptors for agents in a continuous virtual environment. The model uses a
      genetic algorithm (GA) to evolve the agent sensors along with the control of the
      agents by requiring the agents to solve certain tasks in the simulation
      environment. The properties of the evolved sensors are analyzed for different
      scenarios. In particular, it is shown that the GA is able to find a balance
      between sensor costs and agent performance in such a way that the spectral sensor
      sensitivity reflects the emission spectrum of the target objects and that the
      capability of the sensors to evolve can help the agents significantly in adapting
      to their task.

PMID- 11580877
TI  - Evolution of visual resolution constrained by a trade-off.
AB  - The evolution of visual systems is constrained by a trade-off between spatial and
      temporal resolution. In this article we aim at identifying the causes of the
      trade-off at the retinal level in both artificial and natural visual systems. We
      start by selecting two factors that limit the values of spatial and temporal
      resolution. Then we show in two experiments on the evolution of an artificial
      system that the two factors induce trade-off curves connecting the evolved values
      of spatial and temporal resolution. A comparison of the experimental results with
      the resolution evolved in natural visual systems leads us to the conclusion that
      in natural systems the same factors are responsible for the observed trade-off.

PMID- 11580878
TI  - Artificial ears for a biomimetic sonarhead: from multiple reflectors to surfaces.
AB  - This work presents an evolutionary approach to pinna design. Narrowband
      echolocating bats move the pinna to alter the directional sensitivity of their
      perceptual systems. Adding pinnae to RoBat--a biomimetic sonarhead mounted on a
      mobile robot--is the goal of this work. After a description of the earlier work
      on artificial pinnae consisting of multiple reflectors around the transducer, an
      acoustic model, inspired by a physical model of sound diffraction and reflections
      in the human concha, is described and revisited as the model to use for evolving
      complex shapes. A genetic algorithm evolved the shape of the pinnae with respect
      to desired features of the directivity pattern of the receiver transducers. Some
      interesting paraboloid shapes for specific echolocating behaviors were evolved,
      improving performance with respect to the bare transducer's performance.

PMID- 11580879
TI  - Evolving control metabolisms for a robot.
AB  - This article demonstrates a new method of programming artificial chemistries. It
      uses the emerging capabilities of the system's dynamics for information
      processing purposes. By evolution of metabolisms that act as control programs for
      a small robot one achieves the adaptation of the internal metabolic pathways as
      well as the selection of the most relevant available exteroceptors. The
      underlying artificial chemistry evolves efficient information-processing pathways
      with most benefit for the desired task, robot navigation. The results show
      certain relations to such biological systems as motile bacteria.

PMID- 11580880
TI  - Evolving collective behavior in an artificial ecology.
AB  - Collective behavior refers to coordinated group motion, common to many animals.
      The dynamics of a group can be seen as a distributed model, each "animal"
      applying the same rule set. This study investigates the use of evolved sensory
      controllers to produce schooling behavior. A set of artificial creatures "live"
      in an artificial world with hazards and food. Each creature has a simple
      artificial neural network brain that controls movement in different situations. A
      chromosome encodes the network structure and weights, which may be combined using
      artificial evolution with another chromosome, if a creature should choose to
      mate. Prey and predators coevolve without an explicit fitness function for
      schooling to produce sophisticated, nondeterministic, behavior. The work
      highlights the role of species' physiology in understanding behavior and the role
      of the environment in encouraging the development of sensory systems.

PMID- 11580881
TI  - Specialist and generalist strategies in sensory evolution.

PMID- 11580882
TI  - Sympathetic overactivity in hypertension: a risk factor for cardiovascular
      disease.
AB  - Numerous prospective studies have shown that high heart rate is related to the
      development of hypertension, atherosclerosis, and incidence of cardiovascular
      events. Experimental studies in monkeys have shown that high heart rate has
      direct atherogenic effects on the arteries as a result of increased wall stress.
      However, clustering of several risk factors for coronary artery disease in
      persons with high heart rate suggests that sympathetic overactivity also accounts
      for part of the increased cardiovascular morbidity that is observed in persons
      with tachycardia. Indeed, experimental studies have shown that heightened
      sympathetic tone can cause obesity, hyperinsulinemia, and insulin resistance,
      which in the long term can promote the development of atherosclerosis. Through
      its interaction with plasma insulin, sympathetic overactivity can promote the
      development of left ventricular hypertrophy. Sympathetic activation can also
      increase hematocrit and precipitate a procoagulant state. Angiotensin II has an
      effect both on the central nervous system, enhancing sympathetic outflow, and on
      the peripheral sympathetic nerves. Among the angiotensin II receptor antagonists,
      eprosartan showed a particular ability to block presynaptic angiotensin II
      receptor 1 (AT(1)) receptors at neuro-effector junctions in the sympathetic
      nervous system, as well as AT(1) receptors in blood vessels. This dual action may
      represent an important advance in treatment of elevated blood pressure.

PMID- 11580883
TI  - Systolic hypertension and cardiovascular risk reduction: a clinical review.

PMID- 11580884
TI  - Differentiation in the angiotensin II receptor 1 blocker class on autonomic
      function.
AB  - Autonomic function is disordered in cardiovascular disease states such as chronic
      heart failure (CHF) and hypertension. Interactions between the renin-angiotensin
      aldosterone system (RAAS) and the sympathetic nervous system (SNS) may
      potentially occur at a number of sites. These include central sites (eg, rostral
      ventrolateral medulla), at the level of baroreflex control, and at the
      sympathetic prejunctional angiotensin II receptor 1 (AT(1)) receptor, which is
      facilitatory for norepinephrine release from the sympathetic nerve terminal.
      Therefore, drugs that block the RAAS may be expected to improve autonomic
      dysfunction in cardiovascular disease states. In order to test the hypothesis
      that RAAS inhibition directly reduces SNS activity, a pithed rat model of
      sympathetic stimulation has been established. In this model, an increase in
      frequency of stimulation results in a pressor response that is sympathetically
      mediated and highly reproducible. This pressor response is enhanced in the
      presence of angiotensin II and is reduced in the presence of nonselective AIIRAs
      that block both AT(1) and AT(2) receptor subtypes (eg, saralasin). AT(1)
      selective antagonists have also been studied in this model, at pharmacologically
      relevant doses. In one such study, only the AT(1) blocker eprosartan reduced
      sympathetically stimulated increases in blood pressure, whereas comparable doses
      of losartan, valsartan, and irbesartan did not. The reason(s) for the differences
      between eprosartan and other agents of this class on sympathetic modulation are
      not clear, but may relate to the chemical structure of the drug (a non- biphenyl
      tetrazole structure that is chemically distinct from the structure of other
      AIIRAs), receptor binding characteristics (competitive), or unique effects on
      presynaptic AT(1) receptors.

PMID- 11580885
TI  - Potential of the angiotensin II receptor 1 blocker eprosartan in the management
      of patients with hypertension or heart failure.
AB  - When angiotensin-converting enzyme (ACE) inhibition first became available to
      block the renin system, few could have predicted the evolution that would occur
      in this field. The advent of angiotensin II receptor 1 (AT(1)) blockers has
      created new opportunities. These agents, including eprosartan, are
      extraordinarily well tolerated, not only when compared with antihypertensive
      agents but also in comparison with the ACE inhibitors, which are rather well
      tolerated. The AT(1) blocker class is growing rapidly, at least in part because
      many believe that these drugs will share with the ACE inhibitors the special
      ability to reduce morbidity and mortality. Does eprosartan have a special role
      within this class? Eprosartan differs structurally from the other AT(1) blockers
      in that it is not a biphenyl tetrazole. It differs functionally in vitro in being
      a pure competitive antagonist, as opposed to the nonequilibrium, insurmountable
      characteristics of the other blockers. This feature may prove to be useful for
      titration in the fragile patient. The reduction in catecholamine release induced
      by eprosartan that has been observed in animal models may account for some
      special examples of increased efficacy. One such example pertains to the
      difference in the dose-response relationship for the action of eprosartan on the
      renal blood supply in comparison with other AT(1) blockers. Eprosartan doses well
      below those required for control of blood pressure have a pronounced effect on
      the kidney. If research already under way supports these early suggestions, then
      eprosartan will be an important addition to our therapeutic armamentarium.

PMID- 11580886
TI  - Qs in the nucleus.
AB  - The polyglutamine diseases include at least nine neurodegenerative disorders.
      Accumulation of mutant protein with a toxic gain-in function in the nucleus
      appears to be the pathological basis of these diseases. In this issue of Neuron,
      La Spada et al. (2001) provide insight into the cell specificity of pathology for
      a polyglutamine disease by relating SCA7-induced retinal degeneration to a
      disruption of the photoreceptor-specific transcription factor CRX.

PMID- 11580887
TI  - Eph receptors tingle the spine.
AB  - During the development of excitatory synapses, molecules cluster on dendrites to
      form postsynaptic densities, and specialized structures known as spines appear.
      EphB2 is demonstrated to control this process by associating with and
      phosphorylating a key postsynaptic molecule, syndecan-2, thereby initiating the
      maturation of dendritic spines.

PMID- 11580888
TI  - NMDA receptors turn to another channel for inhibition.
AB  - Activation of glutamate receptors generally increases neuronal excitability.
      However, Isaacson and Murphy show in olfactory bulb granule cells that NMDA
      receptor-mediated calcium influx couples to large conductance (BK) calcium
      activated potassium channels. The resulting inhibition is long lasting, which may
      be critical to the operation of the dynamic circuitry of the bulb.

PMID- 11580889
TI  - Radial glial cells. are they really glia?
AB  - During the development of the cerebral cortex, radial glia serve as a scaffold to
      support and direct neurons during their migration. This view is now changing in
      the light of emerging evidence showing that these cells have a much more dynamic
      and diverse role. A recent series of studies has provided strong support for
      their role as precursor cells in the ventricular zone that generate cortical
      neurons and glia, in addition to providing migration guidance.

PMID- 11580890
TI  - Parkin and the molecular pathways of Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disease characterized by the
      selective demise of specific neuronal populations leading to impairment of motor
      functions. Recent genetic studies have uncovered several genes involved in
      inherited forms of the disease. These gene products are implicated in the
      biochemical pathways underlying the etiology of sporadic PD. Mutations in the
      parkin gene causal of autosomal recessive juvenile parkinsonism highlight that
      ubiquitin-mediated proteolysis may play an important role in the pathobiology of
      PD.

PMID- 11580891
TI  - The cortical motor system.
AB  - The cortical motor system of primates is formed by a mosaic of anatomically and
      functionally distinct areas. These areas are not only involved in motor
      functions, but also play a role in functions formerly attributed to higher order
      associative cortical areas. In the present review, we discuss three types of
      higher functions carried out by the motor cortical areas: sensory-motor
      transformations, action understanding, and decision processing regarding action
      execution. We submit that generating internal representations of actions is
      central to cortical motor function. External contingencies and motivational
      factors determine then whether these action representations are transformed into
      actual actions.

PMID- 11580892
TI  - A miniature head-mounted two-photon microscope. high-resolution brain imaging in
      freely moving animals.
AB  - Two-photon microscopy has enabled anatomical and functional fluorescence imaging
      in the intact brain of rats. Here, we extend two-photon imaging from
      anesthetized, head-stabilized to awake, freely moving animals by using a
      miniaturized head-mounted microscope. Excitation light is conducted to the
      microscope in a single-mode optical fiber, and images are scanned using
      vibrations of the fiber tip. Microscope performance was first characterized in
      the neocortex of anesthetized rats. We readily obtained images of vasculature
      filled with fluorescently labeled blood and of layer 2/3 pyramidal neurons filled
      with a calcium indicator. Capillary blood flow and dendritic calcium transients
      were measured with high time resolution using line scans. In awake, freely moving
      rats, stable imaging was possible except during sudden head movements.

PMID- 11580893
TI  - Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod
      dystrophy in a mouse model of SCA7.
AB  - Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disorder caused by
      a CAG repeat expansion. To determine the mechanism of neurotoxicity, we produced
      transgenic mice and observed a cone-rod dystrophy. Nuclear inclusions were
      present, suggesting that the disease pathway involves the nucleus. When yeast two
      hybrid assays indicated that cone-rod homeobox protein (CRX) interacts with
      ataxin-7, we performed further studies to assess this interaction. We found that
      ataxin-7 and CRX colocalize and coimmunoprecipitate. We observed that
      polyglutamine-expanded ataxin-7 can dramatically suppress CRX transactivation. In
      SCA7 transgenic mice, electrophoretic mobility shift assays indicated reduced CRX
      binding activity, while RT-PCR analysis detected reductions in CRX-regulated
      genes. Our results suggest that CRX transcription interference accounts for the
      retinal degeneration in SCA7 and thus may provide an explanation for how cell
      type specificity is achieved in this polyglutamine repeat disease.

PMID- 11580894
TI  - The reelin pathway modulates the structure and function of retinal synaptic
      circuitry.
AB  - The formation of synaptic connections requires the coordination of specific
      guidance molecules and spontaneous neuronal activity. The visual system has
      provided a useful model for understanding the role of these cues in shaping the
      precise connections from the neural retina to the brain. Here, we demonstrate
      that two essential genes in the Reelin signaling pathway function during the
      patterning of synaptic connectivity in the retina. Physiological studies of mice
      deficient in either reelin or disabled-1 reveal an attenuation of rod-driven
      retinal responses. This defect is associated with a decrease in rod bipolar cell
      density and an abnormal distribution of processes in the inner plexiform layer.
      These results imply that, in addition to its essential role during neuronal
      migration, the Reelin pathway contributes to the formation of neuronal circuits
      in the central nervous system.

PMID- 11580895
TI  - Specification of thermosensory neuron fate in C. elegans requires ttx-1, a
      homolog of otd/Otx.
AB  - Temperature is a critical modulator of animal metabolism and behavior, yet the
      mechanisms underlying the development and function of thermosensory neurons are
      poorly understood. C. elegans senses temperature using the AFD thermosensory
      neurons. Mutations in the gene ttx-1 affect AFD neuron function. Here, we show
      that ttx-1 regulates all differentiated characteristics of the AFD neurons. ttx-1
      mutants are defective in a thermotactic behavior and exhibit deregulated
      thermosensory inputs into a neuroendocrine signaling pathway. ttx-1 encodes a
      member of the conserved OTD/OTX homeodomain protein family and is expressed in
      the AFD neurons. Misexpression of ttx-1 converts other sensory neurons to an AFD
      like fate. Our results extend a previously noted conservation of developmental
      mechanisms between the thermosensory circuit in C. elegans and the vertebrate
      photosensory circuit, suggesting an evolutionary link between thermosensation and
      phototransduction.

PMID- 11580896
TI  - Necrotic cell death in C. elegans requires the function of calreticulin and
      regulators of Ca(2+) release from the endoplasmic reticulum.
AB  - In C. elegans, a hyperactivated MEC-4(d) ion channel induces necrotic-like
      neuronal death that is distinct from apoptosis. We report that null mutations in
      calreticulin suppress both mec-4(d)-induced cell death and the necrotic cell
      death induced by expression of a constitutively activated Galpha(S) subunit. RNAi
      mediated knockdown of calnexin, mutations in the ER Ca(2+) release channels unc
      68 (ryanodine receptor) or itr-1 (inositol 1,4,5 triphosphate receptor), and
      pharmacological manipulations that block ER Ca(2+) release also suppress death.
      Conversely, thapsigargin-induced ER Ca(2+) release can restore mec-4(d)-induced
      cell death when calreticulin is absent. We conclude that high [Ca(2+)](i) is a
      requirement for necrosis in C. elegans and suggest that an essential step in the
      death mechanism is release of ER-based Ca(2+) stores. ER-driven Ca(2+) release
      has previously been implicated in mammalian necrosis, suggesting necrotic death
      mechanisms may be conserved.

PMID- 11580897
TI  - Preassociation of calmodulin with voltage-gated Ca(2+) channels revealed by FRET
      in single living cells.
AB  - Among the most intriguing forms of Ca(2+) channel modulation is the regulation of
      L-type and P/Q-type channels by intracellular Ca(2+), acting via unconventional
      channel-calmodulin (CaM) interactions. In particular, overexpressing Ca(2+)
      insensitive mutant CaM abolishes Ca(2+)-dependent modulation, hinting that Ca(2+)
      free CaM may "preassociate" with these channels to enhance detection of local
      Ca(2+). Despite the far-reaching consequences of this proposal, in vitro
      experiments testing for preassociation provide conflicting results. Here, we
      develop a three filter-cube fluorescence resonance energy transfer method (three
      cube FRET) to directly probe for constitutive associations between channel
      subunits and CaM in single living cells. This FRET assay detects Ca(2+)
      independent associations between CaM and the pore-forming alpha(1) subunit of L
      type, P/Q-type, and, surprisingly, R-type channels. These results now
      definitively demonstrate channel-CaM preassociation in resting cells and
      underscore the potential of three-cube FRET for probing protein-protein
      interactions.

PMID- 11580898
TI  - A trimeric protein complex functions as a synaptic chaperone machine.
AB  - We identify a chaperone complex composed of (1) the synaptic vesicle cysteine
      string protein (CSP), thought to function in neurotransmitter release, (2) the
      ubiquitous heat-shock protein cognate Hsc70, and (3) the SGT protein containing
      three tandem tetratricopeptide repeats. These three proteins interact with each
      other to form a stable trimeric complex that is located on the synaptic vesicle
      surface, and is disrupted in CSP knockout mice. The CSP/SGT/Hsc70 complex
      functions as an ATP-dependent chaperone that reactivates a denatured substrate.
      SGT overexpression in cultured neurons inhibits neurotransmitter release,
      suggesting that the CSP/SGT/Hsc70 complex is important for maintenance of a
      normal synapse. Taken together, our results identify a novel trimeric complex
      that functions as a synapse-specific chaperone machine.

PMID- 11580899
TI  - EphB/syndecan-2 signaling in dendritic spine morphogenesis.
AB  - We previously reported that the cell surface proteoglycan syndecan-2 can induce
      dendritic spine formation in hippocampal neurons. We demonstrate here that the
      EphB2 receptor tyrosine kinase phosphorylates syndecan-2 and that this
      phosphorylation event is crucial for syndecan-2 clustering and spine formation.
      Syndecan-2 is tyrosine phosphorylated and forms a complex with EphB2 in mouse
      brain. Dominant-negative inhibition of endogenous EphB receptor activities blocks
      clustering of endogenous syndecan-2 and normal spine formation in cultured
      hippocampal neurons. This is the first evidence that Eph receptors play a
      physiological role in dendritic spine morphogenesis. Our observations suggest
      that spine morphogenesis is triggered by the activation of Eph receptors, which
      causes tyrosine phosphorylation of target molecules, such as syndecan-2, in
      presumptive spines.

PMID- 11580900
TI  - cGMP-mediated facilitation in nerve terminals by enhancement of the spike
      afterhyperpolarization.
AB  - cGMP has long been suspected to play a role in synaptic plasticity, but the
      inaccessibility of nerve terminals to electrical recording has impeded tests of
      this hypothesis. In posterior pituitary nerve terminals, nitric oxide enhanced
      Ca(2+)-activated K+ channel activity by activating guanylate cyclase and PKG.
      This enhancement occurred only at depolarized potentials, so the spike threshold
      remained unaltered but the afterhyperpolarization became larger. During spike
      trains, the enhanced afterhyperpolarization promoted Na+ channel recovery from
      inactivation, thus reducing action potential failures and allowing more Ca(2+) to
      enter. Activating guanylate cyclase, either with applied nitric oxide, or with
      physiological stimulation to activate nitric oxide synthase, increased action
      potential firing. Thus, the cGMP/nitric oxide cascade generates a short-term, use
      dependent enhancement of release.

PMID- 11580901
TI  - Glutamate-mediated extrasynaptic inhibition: direct coupling of NMDA receptors to
      Ca(2+)-activated K+ channels.
AB  - NMDA receptors (NMDARs) typically contribute to excitatory synaptic transmission
      in the CNS. While Ca(2+) influx through NMDARs plays a critical role in synaptic
      plasticity, direct actions of NMDAR-mediated Ca(2+) influx on neuronal
      excitability have not been well established. Here we show that Ca(2+) influx
      through NMDARs is directly coupled to activation of BK-type Ca(2+)-activated K+
      channels in outside-out membrane patches from rat olfactory bulb granule cells.
      Repetitive stimulation of glutamatergic synapses in olfactory bulb slices evokes
      a slow inhibitory postsynaptic current (IPSC) in granule cells that requires both
      NMDARs and BK channels. The slow IPSC is enhanced by glutamate uptake blockers,
      suggesting that extrasynaptic NMDARs underlie the response. These findings reveal
      a novel inhibitory action of extrasynaptic NMDARs in the brain.

PMID- 11580902
TI  - Synchronization of an embryonic network of identified spinal interneurons solely
      by electrical coupling.
AB  - There is a need to understand the mechanisms of neural synchronization during
      development because correlated rhythmic activity is thought to be critical for
      the establishment of proper connectivity. The relative importance of chemical and
      electrical synapses for synchronization of electrical activity during development
      is unclear. We examined the activity patterns of identified spinal neurons at the
      onset of motor activity in zebrafish embryos. Rhythmic activity appeared early
      and persisted upon blocking chemical neurotransmission but was abolished by
      inhibitors of gap junctions. Paired recordings revealed that active spinal
      neurons were electrically coupled and formed a simple network of motoneurons and
      a subset of interneurons. Thus, the earliest spinal central pattern generator
      consists of synchronously active, electrically coupled neurons.

PMID- 11580903
TI  - Dissociating memory retrieval processes using fMRI: evidence that priming does
      not support recognition memory.
AB  - We employed event-related fMRI to constrain cognitive accounts of memory
      retrieval. Studies of explicit retrieval reveal that lateral and medial parietal,
      dorsal middle frontal gyrus, and anterior prefrontal cortex respond more for
      studied than new words, reflecting a correlate of "retrieval success." Studies of
      implicit memory suggest left temporal cortex, ventral and dorsal inferior frontal
      gyrus respond less for studied than new words, reflecting a correlate of
      "conceptual priming." In the present study, responses for old and new items were
      compared during performance on explicit recognition (old/new judgement) and
      semantic (abstract/concrete judgement) tasks. Regions associated with priming
      were only modulated during the semantic task, whereas regions associated with
      retrieval success were modulated during both tasks. These findings constrain
      functional-anatomic accounts of the networks, suggesting that processes
      associated with priming do not support explicit recognition judgments.

PMID- 11580904
TI  - Minerals, trace elements and related biological variables in athletes and during
      physical activity.
AB  - This review concerns various minerals (sodium, potassium, calcium, magnesium,
      phosphorus), trace elements (zinc, manganese, selenium, copper, iron, cobalt,
      iodine, chromium, fluorine, lead, cadmium) and other biological variables (nitric
      oxide, L-carnitine, glutamine, serum transferrin receptor, biopyrrins) in
      relation to hemorheologic effects, stress, immune response and infections during
      physical and sports activities. In athletes, macroelements in the ionized form
      contribute to heart and muscle contractions, oxidative phosphorylation and the
      synthesis and activation of enzymatic systems. Zinc (Zn) protects against the
      effects of increased free reactive oxygen species such as copper (Cu) and
      manganese (Mn) (Cu-Zn superoxide dismutases; Mn superoxide dismutase). Selenium
      in glutathione peroxidase protects the cardiovascular system and the muscles, and
      helps combat allergic and inflammatory diseases. Copper and iron are involved in
      many aspects of energy metabolism and are important components in the synthesis
      of hemoglobin, myoglobin and cytochromes. Fluorine and Cu protect the ligaments
      and tendons. Physical activity appears to be beneficial to urban residents who
      are exposed to metal pollution (lead, cadmium). The data cited in this review are
      often contradictory and incomplete. It is still unclear in many cases how
      minerals are involved in physiological changes, and much work remains.

PMID- 11580905
TI  - Hemopexin: a review of biological aspects and the role in laboratory medicine.
AB  - BACKGROUND: Hemopexin is a heme-binding plasma glycoprotein which, after
      haptoglobin, forms the second line of defense against hemoglobin-mediated
      oxidative damage during intravascular hemolysis. A decrease in plasma hemopexin
      concentration reflects a recent release of heme compounds in the extracellular
      compartment. Heme-hemopexin complexes are delivered to hepatocytes by receptor
      mediated endocytosis after which hemopexin is recycled to the circulation.
      METHODS OF ANALYSIS: Immunonephelometric and -turbidimetric hemopexin assays are
      available as more precise and rapid alternatives to the radial immunodiffusion
      technique. INTERPRETATIONS: Hemopexin determinations are not subject to
      interference by in vitro hemolysis. Altered serum or plasma concentrations of
      hemopexin are found not only in hemolytic anemias but also in other conditions
      such as chronic neuromuscular diseases and acute intermittent porphyria. In
      laboratory medicine, while hemopexin determination in tandem with haptoglobin has
      potential applications in the assessment of intravascular hemolysis and allows
      for the monitoring of the severity of hemolysis after depletion of haptoglobin,
      its diagnostic utility is less clear in other pathological conditions. Further
      studies are necessary to fully establish the clinical significance of hemopexin
      determination.

PMID- 11580906
TI  - 1H-NMR studies of cerebrospinal fluid: endogenous ethanol in patients with
      cervical myelopathy.
AB  - Endogenous ethanol was observed by nuclear magnetic resonance spectroscopy in the
      course of screening for cerebrospinal fluid of the patients with cervical
      myelopathy. Ethanol was detected in 10 out of 20 patients. It seems likely that
      the presence of endogenous ethanol is related to the severity of myelopathy.
      Also, the concentration of ethanol was correlated with that of lactate in the
      cerebrospinal fluid. This implies that ethanol may be formed as the end product
      of glycolysis or in an unknown pathway in the case of severely insulted myelonic
      tissues.

PMID- 11580907
TI  - Cardiac troponin T and C-reactive protein as markers of acute cardiac allograft
      rejection.
AB  - Due to myocyte damage and an associated inflammatory response, it is possible
      that cardiac troponin T and C-reactive protein (CRP) concentrations may correlate
      with the histologic grade of rejection in endomyocardial biopsy samples obtained
      from patients who have received a heart transplant. In this study, 704 blood
      samples were obtained from 145 different heart transplant recipients just prior
      to endomyocardial biopsy. Plasma specimens were assayed for troponin T and CRP
      concentration and the results compared with the assigned International Society of
      Heart and Lung Transplantation (ISHLT) histologic grade. Rejection was defined as
      an ISHLT grade of 3A or higher. The negative predictive values were near 80% in
      all cases, and a statistically significant increase in median troponin T
      concentration was observed across ISHLT grades. After the first month
      posttransplantation, the specificity of the troponin T test (cutoff 0.1 ng/ml)
      was 95% and increased to 98% when false positives seen in renal disease patients
      were excluded. Both tests demonstrated poor sensitivity and positive predictive
      value for rejection. Neither CRP nor troponin T had sufficient sensitivity to
      serve as an alternative to endomyocardial biopsy in the diagnosis of acute
      cardiac allograft rejection. However, the troponin T test had a high specificity,
      especially when patients with renal insufficiency were excluded, and could serve
      as an adjunct test in this setting. When combined with a normal serum creatinine,
      a troponin T > or =0.1 ng/ml prior to endomyocardial biopsy correlated with graft
      rejection in almost all cases, making biopsy unnecessary.

PMID- 11580909
TI  - Detection of anti-lipopolysaccharide antibodies to Vibrio cholerae O1 and O139
      using a novel microtiter limulus amebocyte lysate (LAL) assay.
AB  - This paper describes a new assay for measuring antibodies to lipopolysaccharide
      (LPS) of Vibrio cholerae using blocking of the limulus amebocyte lysate (LAL)
      reaction in a microtiter plate. When V. cholerae LPS was coated onto a microtiter
      plate, and then LAL reagent was added, a typical gel reaction occurred. However,
      when the LPS-coated plates were first incubated with serum containing anti
      cholera antibodies, the gel reaction did not occur. Blocking of the gel reaction
      was serotype specific, in that anti-O1 serum blocked the O1 LAL reaction but not
      the O139 LAL reaction, and anti-O139 serum neutralized the O139 reaction but not
      the O1 reaction. Preliminary data suggested that the LAL titers were comparable
      to the vibriocidal titers but that titers using the LAL assay may have been
      slightly higher. This study showed that antibodies to V. cholerae blocked the LAL
      reaction and suggested that the LAL blocking assay could be applicable for
      determining antibodies to other endotoxin-containing bacteria and microorganisms.

PMID- 11580908
TI  - A double-blind trial on the effects of atorvastatin on glycemic control in
      Japanese diabetic patients with hypercholesterolemia.
AB  - A double-blind, placebo-controlled, parallel-group study was performed to
      determine whether atorvastatin, a new HMG-CoA reductase inhibitor, could
      effectively and safely reduce plasma LDL-cholesterol concentrations in Japanese
      patients with type-2 diabetes without influencing glycemic control. The subjects
      were patients with hypercholesterolemia (serum cholesterol concentration > or
      =5.7 mmol/l (220 mg/dl)) and stable glycemic control. The fasting concentrations
      of hemoglobin A(1C) (HbA(1C)), fructosamine, and 1,5-anhydroglucitol (1,5-AG)
      were measured as indices of glycemic control. Plasma lipid concentrations and the
      safety of the drug were also examined. Forty eligible patients in two groups of
      20 each were administered atorvastatin (10 mg/day) or placebo. Neither
      atorvastatin nor placebo caused a significant change in HbA(1C), fructosamine, or
      1,5-AG concentrations. Atorvastatin significantly reduced total cholesterol and
      LDL-cholesterol concentrations from baseline by 29.7% (p<0.0001) and 41.6%
      (p<0.0001), respectively. The incidence of clinical adverse events and that of
      abnormal changes in laboratory test values did not differ between the two groups.
      In this trial, atorvastatin effectively and safely reduced LDL-cholesterol
      concentrations in diabetic patients with hypercholesterolemia without influencing
      glycemic control. These findings are clinically important because there are many
      diabetic patients with hypercholesterolemia and such patients have a high risk of
      developing arteriosclerotic disease.

PMID- 11580910
TI  - Oxidation of unsaturated fatty acids by human fibroblasts with very-long-chain
      acyl-CoA dehydrogenase deficiency: aspects of substrate specificity and
      correlation with clinical phenotype.
AB  - The degradation of unsaturated fatty acids was examined in fibroblasts from 16
      patients with very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Analysis
      of acylcarnitine intermediates following incubation of intact human cells with
      these compounds revealed that the milder clinical phenotypes could be
      distinguished from the severe cardiomyopathic phenotype. These findings may
      reflect more effective contributions of alternate pathways in the milder forms of
      the disease. Incubation of VLCAD-deficient cells with cis-9 or trans-9
      unsaturated fatty acids indicate that VLCAD is largely responsible for the 2,3
      dehydrogenation of cis-5 or trans-5 intermediates in fibroblasts. The first two
      cycles of beta-oxidation with oleic and linoleic acids occur in the absence of
      VLCAD activity suggesting the presence of an additional acyl-CoA dehydrogenase or
      alternate pathway for the oxidation of these unsaturated fatty acids. These
      observations have clinical relevance for determining diagnosis, prognosis and
      strategies for dietary treatment of these patients.

PMID- 11580912
TI  - Detection of mucopolysaccharidosis type I heterozygotes on the basis of the
      biochemical properties of plasma alpha-L-iduronidase.
AB  - BACKGROUND: Mucopolysaccharidosis type I (MPS I) is a disease caused by
      deficiency of the enzyme alpha-L-iduronidase (IDUA). Since no treatment is
      currently available for this disorder, the detection of heterozygotes is very
      important for genetic counseling and prenatal diagnosis. The objective of the
      present study was to characterize plasma IDUA from MPS I heterozygotes in an
      attempt to distinguish it from that of normal individuals. METHODS: We determined
      the optimum pH, Km, Vmax and Calpha (Vmax/Km) of the reaction and the thermal
      stability of IDUA at 50 degrees C. RESULTS: MPS I heterozygotes can be separated
      from normal individuals on the basis of Km, Calpha and thermal stability of the
      enzyme. CONCLUSIONS: Taking into consideration the clinical status of the
      homozygous offspring, we were able to subdivide the MPS I heterozygotes into
      various subgroups (Hurler, Scheie or Hurler/Scheie compound), and verified that
      the Hurler subgroup had a lower optimum pH for IDUA activity than controls and
      other MPS I subgroups, and that all MPS I subgroups had higher Km and lower
      Calpha when compared to controls.

PMID- 11580911
TI  - Risk stratification using serum concentrations of cardiac troponin T in patients
      with end-stage renal disease on chronic maintenance dialysis.
AB  - BACKGROUND: It has been recently suggested that cardiac troponin T (cTnT) may be
      more sensitive than troponin I (cTnI) for subclinical myocardial cell injury in
      patients on chronic dialysis. METHODS: We prospectively compared the predictive
      value of cTnT with cTnI, atrial (ANP) and brain natriuretic peptide (BNP) in 100
      consecutive outpatients on chronic dialysis without acute coronary syndromes over
      a period of 3 months, and assessed whether the combination of cTnT with clinical
      information including age, duration of dialysis, and medical histories was useful
      for risk stratification of these patients. During the 2-year follow-up period, 19
      patients died, mostly due to cardiac causes (53%). RESULTS: The area under the
      receiver operator characteristic (ROC) curve for the cTnT as predictor of both
      overall and cardiac death was significantly greater than the area under the cTnI
      curve (p < 0.0001 and p = 0.01), the BNP curve (p < 0.001 and p < 0.01) or the
      ANP curve (p < 0.0001 and p < 0.005). In a stepwise multivariate Cox regression
      analysis, only cTnT (p < 0.05 and p < 0.01) and a history of heart failure
      requiring hospitalization (p < 0.05 and p < 0.005) were independent predictors of
      both all cause and cardiac mortality. Using parameters of cTnT > or =0.1 microg/l
      and/or history of heart failure, the overall and cardiac mortality rate for the
      low risk group (n=66) were 4.5% and 1.5%, respectively, 40% and 16% for the
      intermediate risk group (n=25), and 67% and 56% for the high risk group (n=9).
      CONCLUSION: cTnT concentrations offer a higher prognostic accuracy than cTnI, ANP
      and BNP in patients on chronic dialysis. The combination of elevated cTnT and a
      history of heart failure may be a highly effective means of risk stratification
      of these patients.

PMID- 11580913
TI  - Reference intervals for serum apolipoproteins A-I, A-II, B, C-II, C-III, and E in
      healthy Japanese determined with a commercial immunoturbidimetric assay and
      effects of sex, age, smoking, drinking, and Lp(a) level.
AB  - BACKGROUND: Apolipoproteins, which are contained in lipoprotein particles, play
      important roles in the transport of lipids. METHODS: Serum levels of
      apolipoproteins (apo) A-I, A-II, B, C-II, C-III, and E were determined by
      immunoturbidimetry in a healthy Japanese study population (1018 men and 1167
      women, age 20-69 years) to establish reference intervals. RESULTS: Among the 2185
      subjects examined, the mean serum value for apoA-I was 1.42 +/- 0.20 g/l, for
      apoA-II was 0.30 +/- 0.05 g/l, for apoB was 0.87 +/- 0.18 g/l, for apoC-II was 29
      +/- 13 mg/l, for apoC-III was 75 +/- 20 mg/l, and for apoE was 36 +/- 9 mg/l. A
      sex difference was detected in the mean serum concentrations of all six
      apolipoproteins. Alcohol consumption and cigarette use had a slight effect on
      serum apolipoprotein concentrations. Age effects were observed among women in
      apoB, apoC-II, and apoC-III concentrations. Moreover, individuals with elevated
      serum lipoprotein (a) [Lp(a), >300 mg/l] also displayed increased serum apoB and
      apoC-II levels and an increased apoB/apoA-I ratio. CONCLUSION: The reference
      intervals for apolipoproteins in Japanese adults that we established, using
      commercially available reagents for automated analyzers, will be helpful for
      assessing risk of coronary heart disease and pathological conditions of patients
      with hyperlipidemia. We recommend use of these reference intervals for the
      clinical interpretation of serum apolipoprotein concentrations.

PMID- 11580914
TI  - Increased concentrations of 14-3-3 epsilon, gamma and zeta isoforms in
      cerebrospinal fluid of AIDS patients with neuronal destruction.
AB  - BACKGROUND: 14-3-3 proteins are major evolutionarily conserved cytosolic proteins
      that regulate signal transduction, apoptosis and neurotransmitter synthesis. Five
      homologous 14-3-3 isoforms, beta, gamma, zeta, epsilon and eta, are reported in
      mammalian neurones. To elucidate the diagnostic value of 14-3-3 in cerebrospinal
      fluid (CSF), a highly specific antibody against each isoform and studies on the
      isoform patterns in patients with neuronal destruction are needed. METHODS: In
      this study, we raised isoform-specific antibodies against 14-3-3 proteins and
      established a semiquantitative method of identification of each isoform by
      Western immunoblotting. RESULTS: We found that three isoforms, 14-3-3 epsilon,
      gamma and zeta, appeared in the CSF of HIV patients with AIDS dementia complex or
      cytomegalovirus encephalitis, but not in AIDS patients without neurological
      symptoms or the non-HIV patients examined. The isoform patterns in AIDS patients
      were different from those reported in Creutzfeldt-Jakob disease and herpes
      simplex encephalitis, suggesting that the isoform patterns may facilitate the
      differential diagnosis. A high frequency of 14-3-3 in CSF was observed in
      seriously ill AIDS patients, particularly those with CD4 levels of less than 20
      mm(3). CONCLUSION: These findings suggested that 14-3-3 proteins were released
      from destroyed neural cells and are useful real-time markers of the rate and
      amount of neural cell destruction in these patients.

PMID- 11580915
TI  - Methylamine in human urine.
AB  - BACKGROUND: Methylamine is the simplest aliphatic amine found in human urine. In
      the body it is thought to play a significant part in central nervous system
      disturbances observed during renal and hepatic disease and also has a role in
      general toxicity caused by oxidative stress. The present study provides data on
      the daily urinary excretion of methylamine in a population of unrelated healthy
      volunteers and investigates a variety of food substances as potential dietary
      sources. METHODS: Complete 0-24 h urine samples were collected from 203
      volunteers (102 male, age 22.2 +/- 4.5 years, mean +/- S.D.; 101 female, age 21.6
      +/- 5.0 years) maintained on their normal diets. Six male subjects also consumed,
      on different occasions separated by at least 1 week, 41 foods and collected the
      subsequent 0-8 h urine. In addition, these subjects also ingested various dietary
      precursors (betaine, carnitine, choline, creatinine, lecithin) and collected the
      following 0-3 day urine. All urine samples were analysed for their methylamine
      content. RESULTS: The average daily output of methylamine was 11.00 +/- 8.17 mg
      (12.73 +/- 9.35 male; 9.27 +/- 6.35 female) with a range of values spreading from
      1.68 to 62.30 mg. Dietary studies suggested that certain fish and seafoods (clam,
      crab, haddock, halibut, octopus, tuna) and fruit and vegetables (pear, peas,
      tomato) may add to this urinary output. Ingestion of creatinine also increased
      urinary methylamine levels. CONCLUSIONS: For the first time, standard daily
      excretion values for methylamine have been established for a large population.
      Chemical and dietary precursor studies indicated that there was no major
      exogenous source of this amine and suggested that the origin of the majority of
      human urinary methylamine is endogenous with only subtle contributions from the
      diet.

PMID- 11580916
TI  - Human liver disease decreases methacrylyl-CoA hydratase and beta
      hydroxyisobutyryl-CoA hydrolase activities in valine catabolism.
AB  - BACKGROUND: Methacrylyl-coenzyme A (MC-CoA) hydratase and beta-hydroxyisobutyryl
      coenzyme A (HIB-CoA) hydrolase are key enzymes regulating the toxic concentration
      of MC-CoA generated in valine catabolism. MATERIALS AND METHODS: We studied the
      activities and mRNA expression levels of these enzymes in normal human livers and
      in human livers with chronic hepatitis, cirrhosis, or hepatocellular carcinoma.
      RESULTS: The activities of both enzymes were significantly lower by 36% to 46% in
      livers with cirrhosis or hepatocellular carcinoma compared with normals,
      suggesting a decrease in the capability of detoxifying MC-CoA with these
      diseases. The mRNA levels for both enzymes measured by quantitative polymerase
      chain reaction were significantly increased in livers with cirrhosis, but were
      not altered in those with chronic hepatitis or hepatocellular carcinoma when
      compared with normal livers. CONCLUSION: Our results suggest that low levels of
      these enzyme activities in livers with cirrhosis or hepatocellular carcinoma are
      the result of posttranscriptional regulation in the damaged liver.

PMID- 11580917
TI  - Assessment of copper status in pregnancy by means of determining the specific
      oxidase activity of ceruloplasmin.
AB  - BACKGROUND: Conditions not directly related to copper nutriture, such as
      pregnancy, infections and inflammation, which increase serum copper concentration
      even during copper deprivation, may be expected to conceal changes in copper
      status. It has been suggested that the specific enzymatic activity of
      ceruloplasmin (activity per unit mass of enzyme protein) may be a sensitive
      indicator of copper status and is not affected by factors such as hormones or
      sex. In this study, we investigated the behaviour of specific oxidase activity of
      ceruloplasmin and the copper/ceruloplasmin ratio in pregnant women. METHODS:
      Copper, immunoreactive ceruloplasmin and its oxidase activity were determined in
      serum from 52 women in the last trimester of normal pregnancy, and in 50 control
      women of similar age living in the same area and who were not taking oral
      contraceptives. The results are expressed as mean+/-S.E.M. RESULTS: In the group
      of pregnant women, significantly higher serum levels of copper, ceruloplasmin and
      its oxidase activity were found than in the control group (p < 0.001). In both
      groups, a high correlation was found between these biochemical variables (r > or
      =0.905, p < 0.001). However, in the group of pregnant women the specific oxidase
      activity for ceruloplasmin (364.4+/-3.3 vs. 407.5+/-3.8 U/g) and the
      copper/ceruloplasmin ratio (2.82+/-0.03 vs. 3.19+/-0.04 microg/mg) were
      significantly lower than in the control group (p < 0.001). CONCLUSIONS: Although
      pregnancy accelerates the rate of ceruloplasmin protein synthesis and release
      with an increase of serum copper, the decrease in specific oxidase activity of
      circulating ceruloplasmin would be an indicator of the degree of depletion of the
      mother's copper deposits in order to deal with the foetus' needs.

PMID- 11580918
TI  - Amperometric creatinine biosensor for hemodialysis patients.
AB  - BACKGROUND: Creatinine is an important clinical laboratory parameter for the
      evaluation of kidney function. It is essential to determine its concentration in
      serum of patients suffering from renal insufficiency. During hemodialysis
      treatment, the measurement of creatinine in the effluent dialysate or
      ultrafiltrate may give additional information on the efficiency of the
      extracorporal procedure. Therefore, enzyme sensors with co-immobilized creatinine
      amidohydrolase, creatine amidinohydrolase and sarcosine oxidase have been used to
      determine creatinine. METHODS: Enzymatically generated hydrogen peroxide has
      amperometrically been detected at a platinum-working electrode. To exclude
      electroactive compounds of the sample matrix, which might interfere with the
      electrochemical measurement, the sensors have additionally been modified by a
      Nafion membrane. RESULTS: Such sensors showed a linear detection range of 0.06
      1.7 mg/dl for creatinine. Diluting the sample with measuring buffer, it has also
      been possible to measure pathological creatinine concentrations up to 11 mg/dl. A
      good correlation between creatinine concentrations in serum, dialysate and
      ultrafiltrate determined by the presented enzyme sensors and those obtained by
      both, conventional colorimetric Jaffe and enzymatic measurements have been
      achieved. CONCLUSION: Further developments will aim at the integration of this
      measuring principle into the concept to low-cost disposable planar sensors.

PMID- 11580919
TI  - Colorectal cancer metastatic phenotype stimulates production by fibroblasts of N
      terminal peptide of type III collagen: clinical implications for prognosis.
AB  - In this study we assessed whether the serum levels of the N-terminal peptide of
      type III collagen (PIIIP), an index of type III collagen synthesis, are
      influenced by colorectal cancer stage, and whether "in vitro" fibroblast growth
      and PIIIP production could be altered by tumor tissues obtained from metastatic
      and nonmetastatic colorectal cancer. 208 colorectal cancer patients (115 colon
      and 93 rectum) were studied; 54 were stage I, 62 stage II, 37 stage III and 55
      stage IV. PIIIP serum levels were significantly higher in stage IV as compared to
      all other patient groups. The 5-year survival of stage I, stage II, stage III and
      stage IV patients were 87%, 88%, 32% and 20%, respectively. In the subgroup of
      stage I and stage II patients considered together, PIIIP (> 0.5 U/ml), but not
      CEA (> 5 microg/l) serum levels, were predictive for survival. Fibroblast growth
      was significantly inhibited, while PIIIP production was significantly enhanced,
      when these cells were conditioned with colorectal cancer homogenates obtained
      from patients with distant metastases, than from those without distant
      metastases. In conclusion, colorectal tumors, when metastatic, stimulate
      fibroblasts' PIIIP synthesis and the serum levels of this peptide might predict
      patients' outcome after radical surgery.

PMID- 11580920
TI  - An enzymatic cycling method for the measurement of myo-inositol in biological
      samples.
AB  - INTRODUCTION: A sensitive and simple enzymatic cycling method is described for
      the quantitation of myo-inositol in biological samples. METHODS: The method
      involves the use of a sensitive and simple enzymatic cycling method is described
      for the quantitation of myo-inositol in biological samples. The method involves
      use of thio-NAD(+), NADH and thermostable myo-inositol dehydrogenase (IDH; EC.
      1.1.1.18) and measurement of the increase in absorbance at 405 nm of thio-NADH at
      37 degrees C. RESULTS: The calibration curve for myo-inositol was linear (r=1.00)
      between 10 and 400 micromol/l. Analytical recoveries of exogenous myo-inositol
      added to serum and urine were 100-105% and 98-103%, respectively. Within-run and
      between-run coefficient of variation (CV) were 0.6-2.1% and 1.1-3.0%,
      respectively. This method was free from interference by hemoglobin, bilirubin,
      ascorbate, chyle, various sugars, sugar alcohol and myo-inositol phosphates. With
      the use of myo-inositol as a standard solution, the serum myo-inositol
      concentration (mean+/-SD) was significantly greater in patients with diabetes
      mellitus (DM) without nephropathy (73.0+/-13.8 micromol/l, n=7) than in healthy
      individuals without DM (61.0+/-12.4 micromol/l, n=20). The urinary myo-inositol
      concentration was also significantly greater in patients with DM without
      nephropathy (793.3+/-870.3 micromol/l, n=7) than in healthy individuals without
      DM (76.0+/-63.0 micromol/l, n=13). CONCLUSIONS: This new method is simple,
      sensitive and enables quantitative analysis of myo-inositol.

PMID- 11580921
TI  - Quantitative amino acid analysis using a Beckman system gold HPLC 126AA analyzer.
AB  - BACKGROUND: The Beckman 6300/7300 analyzer, which was widely used for amino acid
      (AA) analysis, is no longer commercially available. METHODS: To set up an
      affordable AA analysis program, a Beckman system gold HPLC 126AA analyzer and
      Pickering Laboratories reagents were used. Two quantitative AA analysis programs
      were developed. One was an 18-min short program quantitating seven AAs from
      plasma and dried blood spots (DBS) specimens using Lithium eluents Li-365 and Li
      375 at 70 degrees C column temperature. The short program could be used for
      diagnosis and follow-up dietary management for phenylketonuria (PKU), maple syrup
      urine disease (MSUD), tyrosinemia and homocystinuria patients. The second program
      was a 118-min long AA screening panel quantitating 40 AAs using Lithium eluents
      Li-275, Li-365 and Li-375 at 32, 48 and 72 degrees C column temperatures from
      plasma and urine specimens. RESULTS: The values obtained from DBS specimens were
      in good agreement with certified results from the Centers for Disease Control and
      Prevention. The values obtained from plasma and urine samples were in good
      correlation with those obtained from Beckman 6300 analyzer (0.9076 < or = r < or
      = 0.999). CONCLUSIONS: Amino acid quantitation from physiological samples using a
      Beckman 126AA Analyzer and Pickering Laboratories reagents was useful for
      clinical diagnosis and monitoring of aminoacidopathies.

PMID- 11580922
TI  - Acanthopanax senticosus root inhibits mast cell-dependent anaphylaxis.
AB  - BACKGROUND: Mast cells synthesize and secrete chemical mediators which play a
      central role in anaphylaxis. METHODS: The effect of Acanthopanax senticosus root
      (ASR) on mast cell-dependent anaphylaxis was investigated. RESULTS: ASR inhibited
      compound 48/80-induced systemic anaphylactic shock at the dose of 1.0 g/kg by
      50%. When ASR was given as pre-treatment at concentrations ranging from 0.01 to
      2.0 g/l, the histamine release from rat peritoneal mast cells induced by compound
      48/80 was reduced in a dose-dependent manner. ASR (2.0 g/kg) also inhibited
      passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE to
      53.17+/-6.62%. Moreover, ASR inhibited tumor necrosis factor-alpha production in
      a concentration-dependent manner, and the treatment of 1 g/l blocked the
      production by 32.5+/-3.50% compared to saline value. CONCLUSIONS: ASR may possess
      effective anti-anaphylactic activity.

PMID- 11580923
TI  - Atypical alkaline phosphatase isozymes in serum and urine of patients with renal
      failure.
AB  - BACKGROUND: Alkaline phosphatases (ALPs) originating from different organs are
      frequently detected in the serum and urine of patients with renal failure.
      METHODS: We investigated the characteristics of ALPs in the serum and urine of
      108 patients with chronic renal failure (CRF) and of 106 healthy control
      subjects. RESULTS: In polyacrylamide gel electrophoresis, three atypical ALP
      bands in serum of patients were designated as atypical-s1, -s2 and -s3,
      respectively. In contrast, five atypical bands (u1, u2, u3, u4 and u5) were
      detected in the urine of patients. The atypical ALPs were electrophoretically
      isolated and assayed to determine their biochemical properties, i.e.,
      neuraminidase sensitivity, heat stability, reactivity to anti-intestinal or anti
      tissue nonspecific ALP antibodies, molecular sizes and sugar chain
      heterogeneities. From these results, we found that atypical-s1 and -s2 were the
      intestinal-type ALP, while s3 was the tissue-unspecific type ALP. Atypical-u1, 
      u2 and -u3 were high-molecular type ALPs, which we suggested as the ones that
      originated from the intestine. Atypical-u4, a tissue-unspecific type ALP, was
      detected with considerable frequency in the urine of patients. In patients with
      CRF, the appearance of these atypical ALPs was accompanied by a deterioration of
      the creatinine clearance. CONCLUSIONS: The appearance of atypical ALPs in the
      serum and urine of patients with CRF may be a useful marker for renal disease.

PMID- 11580924
TI  - Serum platelet-activating factor acetylhydrolase (PAF-AH) activity in more than
      3000 healthy Japanese.
AB  - BACKGROUND: A spectrophotometric assay for platelet-activating factor
      acetylhydrolase (PAF-AH) activity differs from the radioisotopic assay in its
      value because of a difference in substrate specificity. The spectrophotometric
      assay is more precise than the radioisotopic assay, providing information that is
      not clear with the radioisotopic assay. METHODS: We measured the serum PAF-AH
      activity in 3106 healthy Japanese, utilizing the spectrophotometric assay with an
      Hitachi 7170 automatic analyzer. We also measured the serum PAF-AH activity in 18
      healthy volunteers to investigate the effect of diet and the change in activity
      in a day and over 6 weeks. Changes were examined at 0 (day 1), 1, 2, 4 and 6
      weeks. RESULTS: The mean value for females was significantly lower than that of
      males at the 5% level and both male and female activity had a tendency to
      increase with advancing age. It is known that the PAF-AH is primarily associated
      with LDL in blood and the PAF-AH activity correlated with the total cholesterol
      (r=0.52, n=126) and the LDL cholesterol (r=0.60, n=126) concentrations. In the
      diet study, there was no observable effect on activity. No difference in PAF-AH
      activity was observed between serum and plasma sample types. The serum PAF-AH
      activity was stable at 7 degrees C for at least 7 days and at -20 degrees C for
      at least 2 months. CONCLUSIONS: The serum PAF-AH activity in women was lower than
      in men until the menopausal age was reached. We could use not only fresh fasting
      serum, but also plasma sample, non-fasting sample and stored sample to estimate
      the PAF-AH activity.

PMID- 11580925
TI  - Comparison of protein carbonyl and antioxidant levels in brain tissue from
      intracerebral haemorrhage and control cases.
AB  - BACKGROUND: In an attempt to develop a clearer understanding of the pathological
      mechanisms underlying intracerebral haemorrhage (ICH), the objective of this
      investigation was to obtain evidence for free radical-induced oxidative damage in
      brain tissue following intracerebral haemorrhage. METHODS: Brain cortex samples
      were obtained from the ischaemic penumbra (overlying the haematoma) from 10
      patients with spontaneous ICH and from six control cases (normal tissue obtained
      during tumour removal or aneurysm repair). Following extraction via
      homogenization and subsequent derivatization with dinitrophenylhydrazine (DNPH),
      tissue samples were analysed for the presence of protein carbonyl moieties (a
      hallmark of tissue protein oxidation). This procedure involved SDS-polyacrylamide
      gel electrophoresis and Western immunoblotting using a commercially available
      primary monoclonal antibody to DNPH, with final visualization of oxidized protein
      bands via enhanced chemiluminescence. RESULTS: Samples from ICH cases showed a
      number (10-15) of well-defined bands of medium to strong staining intensity (not
      present in nonderivatized samples), corresponding to proteins of molecular mass
      25-200 kDa, indicating the presence of oxidatively damaged proteins in these
      samples. However, tissue samples from control cases also showed the presence of
      oxidized protein bands, with fractionation patterns for individual ICH or control
      samples being qualitatively and quantitatively similar. In addition, there was no
      significant difference in the levels of the following antioxidants (as additional
      indirect markers of free radical activity) in ICH or control brain tissue:
      glutathione, glutathione peroxidase, glutathione reductase, catalase, superoxide
      dismutase, and total antioxidant status. CONCLUSIONS: It is concluded from the
      above data that (i) evidence for free radical involvement in ICH based on protein
      carbonyl analysis should be interpreted with caution, since normal brain tissue
      contains a surprisingly high proportion of oxidized proteins; (ii) since there is
      no evidence for increased protein oxidative damage or decreased tissue
      antioxidant levels in ICH, therapeutic strategies aimed at salvage of potentially
      viable tissue would not benefit from inclusion of protein protecting
      antioxidants.

PMID- 11580926
TI  - Effects of apolipoprotein E genotypes and other risk factors on the development
      of coronary artery disease in Southern Turkey.
AB  - BACKGROUND: Apolipoprotein E (apoE) plays a major role in lipoprotein metabolism
      and lipid transport. Associations between apoE genotypes, coronary artery disease
      (CAD) and other risk factors have been described by many investigators. The aim
      of this study was to investigate the role of apoE gene polymorphism and other
      risk factors in the development of CAD in subjects whose coronary arteries were
      evaluated by means of coronary angiography. METHODS: The study population
      consisted of 199 subjects (114 male and 55 female). Of the total, 107 had CAD.
      The apoE gene was amplified by polymerase chain reaction (PCR) and then digested
      by CfoI restriction enzyme. The plasma lipid levels and other risk factors were
      also determined in all subjects. RESULTS: The epsilon2 and epsilon4 allele
      frequencies and genotypes carrying epsilon4 allele were significantly higher in
      CAD (+) patients. Plasma lipids except triglycerides were increased in CAD (+)
      cases. We found that apoE genotypes, HT, DM, male gender, age and smoking were
      the independent predictors of CAD. There was no association between apoE alleles
      and lipids. CONCLUSION: We conclude that apoE polymorphism (presence of epsilon4
      allele) is associated with the development of CAD in Southern Turkey. In our
      study, we did not observe any effect of apoE alleles on lipid levels.

PMID- 11580927
TI  - Magnesium concentration in plasma, leukocytes and urine of children with
      intermittent asthma.
AB  - BACKGROUND: Magnesium (Mg) is involved in numerous physiological functions,
      including protein folding, intracellular signalling and enzyme catalysis. It acts
      as a smooth muscle relaxant. We decided to test changes of total Mg concentration
      in plasma, leukocytes and urine of 16 healthy children and 26 patients with
      intermittent asthma aged 3 to 14 years. METHODS: Samples were taken on the first
      day of broncho-obstruction and five days after the acute attack. During this
      period, patients were under salbutamol therapy. RESULTS: Plasma Mg concentration
      in patients increased by about 40% (first day 0.58+/-0.05 mmol Mg/l and five days
      later 0.64+/-0.04 mmol Mg/l) compared with healthy children (0.42+/-0.04 mmol
      Mg/l). Leukocyte Mg concentrations showed significant changes. On the first day
      of broncho-obstruction, Mg in leukocytes significantly decreased by about 60%
      (1.16+/-0.31 mmol Mg/g protein) compared to healthy children (3.04+/-0.68 mmol
      Mg/g protein). Five days later, Mg values significantly increased (3.28+/-1.09
      mmol Mg/g protein) and almost reached the values of the healthy group. Mg
      concentration in urine statistically decreased by about 30% (0.55+/-0.06 mmol
      Mg/mmol creatinine) on the first day of broncho-obstruction compared to healthy
      children (0.75+/-0.05 mmol Mg/mmol creatinine). Five days after the acute attack,
      Mg concentration in patients' urine (0.73+/-0.07 mmol Mg/mmol creatinine) was
      close to values of healthy children. CONCLUSION: The results obtained indicate
      that the intracellular measurement of Mg concentration is relevant for estimation
      of magnesium concentration in the human organism. Hence, determination of Mg
      concentration in leukocytes may be used in evaluation of asthmatic pathology.

PMID- 11580928
TI  - Sources of interference in the use of 2,3-diaminonaphthalene for the fluorimetric
      determination of nitric oxide synthase activity in biological samples.
AB  - The use of 2,3-diaminonaphthalene (DAN) for the fluorimetric determination of
      nitric oxide synthase (NOS) activity in rat brain extracts has been re-examined.
      Two types of interference were observed, due either to components of the reaction
      mixture or to the enzymatic sample itself. One of the substrates (NADPH) and some
      cofactors (FADH(2), FMNH(2)) required for the enzyme activity interfere in the
      assay by quenching the fluorescence produced. Interference was minimized by using
      lower FADH(2), FMNH(2) and NADPH concentrations (1 micromol/l) and a NADPH
      recycling system in the reaction mixture. The addition of bovine serum albumin or
      hemoglobin to the sample quenched fluorescence intensity, but these protein
      interferences could be reduced by filtering the samples after reaction. We
      conclude that the DAN fluorimetric assay as originally described is not suitable
      for the determination of NOS activity in crude extracts such as rat brain
      cytosolic fraction, due to the presence of interfering substances. Nevertheless,
      DAN could be used for the determination of enzyme activity after reducing protein
      interference by filtering, or in less complex samples such as cell cultures (e.g.
      activated macrophages), or in chromatographic fractions obtained during the
      purification of the enzyme. A careful use of the commercial kits based on the use
      of DAN for the determination of NOS activity is recommended.

PMID- 11580929
TI  - Effects of natural products and nutraceuticals on steroid hormone-regulated gene
      expression.
AB  - BACKGROUND: There is an increasing trend in the use of complementary and
      alternative therapies to treat or prevent hormonally dependent pathologies.
      Methods determined whether several of these natural products and nutraceuticals,
      commonly taken for hormone-related effects, possess steroid hormone activity. The
      agonist and antagonist estrogenic, androgenic, and progestational activities of
      20 natural products and nutraceuticals were assessed using an in vitro tissue
      culture indicator system. Two steroid-regulated proteins (pS2 and prostate
      specific antigen [PSA]) were quantified, using ELISA-type immunoassays, as
      markers of agonist and antagonist activity. RESULTS: Four of the products tested,
      two isoflavone preparations, Promensil and Estro-Logic, chamomile, and grapeseed
      extracts, were found to have weak estrogenic agonist activity, with the latter
      two also demonstrating weak progestational activity. Several of the products
      tested exhibited antagonistic (blocking) activity, including antiestrogenic
      activity by Prostate-Ease, wild yam root, and dong quai, and antiandrogenic
      activity by dong quai, Promensil, and rosehips. CONCLUSIONS: Several of these
      natural products demonstrate weak steroid hormone activity.

PMID- 11580930
TI  - Determination of vancomycin in human serum by micellar electrokinetic capillary
      chromatography with direct sample injection.
AB  - BACKGROUND: Vancomycin (VCM) has a bacteriostatic effect on gram-positive
      bacteria such as the methicillin-resistant Staphylococcus aureus. METHODS: A new
      assay for measuring vancomycin concentration by micellar electrokinetic capillary
      chromatography using direct serum injection was developed. A borate buffer (pH
      10.0) containing 100 mmol/l sodium dodecyl sulfate was used as an electrophoresis
      buffer, and the detection was at 210 nm. The migration time of vancomycin was
      approximately 7 min. RESULTS: The linearity was from 0 to 100 microg/ml, with the
      limit of detection of 1.0 microg/ml (S/N=3). The within-run CV was 3.99-5.53%,
      and the recovery rate was 91-103% for a concentration range of 6.5-45.5
      microg/ml. The between-day CV was 6.76% at 22.2 microg/ml. There was no
      interference from 32 other antibiotics. The correlation coefficient between the
      assay and fluorescence polarization immunoassay and direct injection HPLC was
      0.982 and 0.985, respectively. The assay required no sample preparation of serum
      and used only microquantities of an electrophoresis buffer and samples.
      CONCLUSIONS: This assay is cost-effective and suitable for routine clinical use.

PMID- 11580931
TI  - Plasma total glutathione concentrations in healthy pediatric and adult subjects.
AB  - Glutathione, as a free radical scavenger, plays an important role in protecting
      cells against oxidative damage. Since aging is associated with decreased plasma
      glutathione levels, we investigated plasma concentrations of total glutathione
      (including the reduced and oxidized forms, tGSH=GSH+GSSG) and total cysteine in
      129 healthy pediatric and adult subjects. Plasma tGSH concentrations were
      significantly lower in infants than in adults. There were no significant
      differences in plasma tGSH concentrations between the children and adult group.
      No significant differences in plasma total cysteine concentrations were found
      between any pediatric and adult group. We conclude that lower plasma tGSH levels
      in pediatric subjects may reflect greater oxidative stress during the neonatal
      and infant period.

PMID- 11580933
TI  - Reoperation rates for acute graft extrusion and pseudarthrosis after one-level
      anterior corpectomy and fusion with and without plate instrumentation: etiology
      and corrective management.
AB  - BACKGROUND: Reoperation rates after one-level anterior cervical corpectomy with
      fusion (ACF) performed without and with plates need further evaluation. METHODS:
      Reoperation rates for graft extrusion and symptomatic pseudarthrosis were
      analyzed following 48 nonplated (1989-1996) and 35 plated (1997-2000) one-level
      ACF. Preoperatively, patients typically exhibited mild/moderate myelopathy
      attributed to spondylostenosis and ossification of the posterior longitudinal
      ligament (OPLL). Thirty-five ACF were performed with plates: 3 Orion, 12
      Atlantis, and 20 ABC Aesculap plates. Fusion was documented on both dynamic X
      rays and 2- or 3-dimensional CT studies 3 and 6 months postoperatively, or until
      fusion occurred. Follow-up averaged 82 months for the nonplated patients, and 21
      months for the plated patients. RESULTS: Out of 48 nonplated patients, 3
      developed immediate graft extrusions within 24 hours of surgery requiring graft
      replacement. Another 2 exhibited symptomatic pseudarthrosis 6 months
      postoperatively, and required secondary posterior wiring with fusion (PWF). In
      comparison, 1 of the 35 patients with plated one-level ACF developed plate
      displacement 6 weeks postoperatively, while 3 exhibited symptomatic
      pseudarthrosis 6 months after surgery, and required secondary posterior wiring
      and fusion (PWF). CONCLUSIONS: Comparison of one-level ACF performed with and
      without plates showed that plating did not appear to reduce pseudarthrosis or
      graft extrusion rates.

PMID- 11580939
TI  - Multiple intracranial lesions in head injury: clinical considerations, prognostic
      factors, management, and results in 95 patients.
AB  - BACKGROUND: The goal of this study was to identify clinical and radiological
      predictors of prognosis in patients with multiple post-traumatic intracranial
      lesions. METHODS: We reviewed 95 patients (75 male and 20 female) between the
      ages of 18 and 70 (average 38) admitted between 1993 and 2000 with multiple post
      traumatic intracranial lesions. Intracranial pressure (ICP) monitoring was
      carried out in 67 patients (70%); 77 received intensive care unit (ICU)
      treatment. Since in all cases it was possible to identify a clearly predominant
      lesion, 3 groups of patients emerged from the data: the first with extradural
      hematoma (EDH), the second with a combination of homolateral subdural (SDH) and
      intracerebral hematoma (ICH), and the third with pure focal intracerebral
      hematoma (ICH). RESULTS: Twenty-seven patients were treated conservatively, 2 of
      whom died (7.4%); both had bilateral ICH and compression of the basal cisterns.
      Sixty-eight patients underwent one or more surgeries; 8 died (11.7%). In the
      group with EDH-predominant lesions (27 cases) all patients were operated (16 for
      multiple lesions); no one died. In the group with SDH+ICH-predominant lesions, 26
      of 32 patients were operated (10 had multiple procedures); 6 died (18.7%), 3 were
      vegetative. In the group with ICH-predominant lesion, 15 of 36 patients were
      operated (7 bilaterally); 4 died (11%). Decompressive craniectomy proved to be a
      useful means to control ICP. Bilateral lobectomy is not recommended because of
      poor results. Immediate postoperative computed tomography (CT) scan proved to be
      mandatory to detect additional surgically treatable lesions (16 cases).
      Statistical analysis was performed by means of chi(2) analysis and multiple
      linear regression model. The multiple linear regression model was used to
      ascertain risk factors independently associated with the outcome. The type of
      lesion (presence of SDH+ICH predominant lesion), the worst recorded Glasgow Coma
      Scale (GCS) score, the presence of prolonged increased ICP, and the absence of
      pupillary reflexes were all statistically significant predictors of a bad outcome
      (dead or vegetative state). CONCLUSIONS: Multiple lesions have the same prognosis
      as the corresponding single lesions; therefore, their management should be guided
      by the predominant pathology.

PMID- 11580941
TI  - Effect of bilateral subthalamic electrical stimulation in Parkinson's disease.
AB  - BACKGROUND: Bilateral high frequency subthalamic stimulation has been reported to
      be effective in the treatment of Parkinson's disease and levodopa-induced
      dyskinesias. To analyze the results of this surgical procedure we critically
      reviewed 17 parkinsonian patients with advanced disease complicated by motor
      fluctuations and dyskinesias. METHODS: Between January 1998 and June 1999 these
      17 consecutive patients (age 48-68 years; illness duration 8-27 years) underwent
      bilateral stereotactically guided implantation of electrodes into the subthalamic
      nucleus in the Department of Neurosurgery of the Istituto Nazionale Neurologico
      "C. Besta." Parameters used for continuous high-frequency stimulation were:
      frequency 160 Hz, pulse width 90 microsec, mean amplitude 2.05 +/- 0.45 V. Parts
      II and III of the UPDRS were used to assess motor performance before and after
      operation by the neurologic team. The follow-up ranged between 6 and 18 months.
      RESULTS: At latest examination, mean UPDRS II and III scores had improved by 30%
      (on stimulation, off therapy) with mean 50% reduction in daily off time. Peak
      dyskinesias and early morning dystonias also improved in relation to therapy
      reduction. Side effects were persistent postoperative supranuclear oculomotor
      palsy and postural instability in one case, worsened off-medication hypophonia in
      three, and temporary nocturnal confusion episodes in three. Postoperative MRI
      revealed a clinically silent intracerebral haematoma in one case. One electrode
      required repositioning. CONCLUSIONS: Continuous high frequency STN stimulation is
      an effective treatment for advanced PD. A functionally useful and safe electrode
      placement can be performed without microrecording.

PMID- 11580945
TI  - Intra-axial dermoid/epidermoid tumors of the brainstem in children.
AB  - BACKGROUND: Epidermoid and dermoid cysts are rare intracranial space-occupying
      lesions, which account for about 1% of all intracranial tumors; they are even
      rarer in the pediatric age group. Among the various locations, that inside the
      brain stem is quite exceptional (only 12 cases reported to date in the
      literature). We report two additional cases occurring in children, underlining
      their clinical characteristics, the difficulties faced in the diagnostic work-up,
      and the surgical treatment adopted (which consisted of removal of the cyst
      contents and partial resection of the cyst membrane, because of its adherence to
      the surrounding nervous and vascular structures). METHODS: We report two cases of
      intraaxial dermoid/epidermoid cysts observed within the last 5 years. Both
      patients complained of cervico-nuchal pain, with a remittent/intermittent
      character in one of them; this patient also exhibited transient 6th and 7th
      cranial nerve deficit. One lesion was approached through the floor of the fourth
      ventricle, the second one through the ventrolateral aspect of the brainstem.
      RESULTS: Subtotal tumor resection was achieved in both cases. Both patients had a
      smooth postoperative course without permanent neurological deficits. In the first
      patient residual tumor remains stable on follow-up MRI. In the second one, early
      tumor regrowth necessitated a second operation, after which the residual tumor
      has remained stable. CONCLUSIONS: Based on our experience we suggest that a
      cautious surgical approach ("conservative" resection) to these lesions is the
      best choice. In fact, attempts at radical removal carry unacceptably high
      morbidity and mortality rates.

PMID- 11580947
TI  - Transoral transclival removal of anteriorly placed cavernous malformations of the
      brainstem.
AB  - BACKGROUND: The natural history of brain stem cavernous malformations is
      unfavorable because of their high hemorrhage rate and resulting neurological
      deterioration among patients. However, direct surgery of intrinsic and anteriorly
      situated cavernomas is hazardous and leads to a bad postoperative outcome because
      of trauma to lateral and dorsally situated eloquent areas of the brain stem.
      METHODS: We review the cases of two patients with symptomatic cavernous
      malformations of the anterior brain stem and describe the usefulness of a
      transoral-transclival approach. A 23-year-old man developed progressive
      hemihypaesthesia and paraesthesia, hemiparesis with gait ataxia, dysarthria,
      dysphonia, and dysphagia. A 38-year-old woman suffered from an acute onset of
      vertigo with nausea and vomiting, diplopia, and paraesthesia of the left hand and
      foot. In both patients, computed tomography demonstrated the presence of brain
      stem hemorrhage, because of cavernous malformation. Magnetic resonance imaging
      showed a close proximity of the lesions to the pia mater only on the ventral
      surface of the brain stem. RESULTS: In both patients, the cavernomas could be
      safely approached and completely resected via a transoral transclival route.
      Three months after surgery, neurological examination revealed marked neurological
      improvement. The 23-year-old patient showed slight gait ataxia, no hemiparesis,
      no cranial nerve palsies; the 38-year-old woman demonstrated no neurological
      symptoms except for minimal motor dysfunction of the left hand. In both cases,
      under perioperative prophylactic antibiotics, no meningitis was observed. The
      patients could subsequently return to their previous employment. CONCLUSION: The
      transoral transclival approach for ventrally situated brain stem cavernomas
      allows a largely atraumatic resection of the lesion.

PMID- 11580951
TI  - Radiosurgery of cavernous hemangiomas in the cavernous sinus.
AB  - BACKGROUND: Cavernous hemangiomas in the cavernous sinus are rare and demonstrate
      unique clinical courses. Although they rarely cause spontaneous bleeding, serious
      bleeding is not uncommon during operations. Total eradication of such tumors is
      very difficult because of the location and intraoperative bleeding. Consequently,
      alternatives to operative resection have been examined. METHODS: Three cases of
      cavernous hemangiomas in the cavernous sinus, presenting chiefly with ocular
      signs and facial pain, were treated by radiosurgery using a gamma knife. Two of
      the patients had been operated on before radiosurgery, while the third patient
      was diagnosed on the basis of neurological signs as well as radiological
      findings. RESULTS: MRI scans at the time of radiosurgery showed tumors in the
      cavernous sinus with low or iso-intensity on T1-weighted images and high signal
      intensity on T2-weighted images. All of the tumors intensely enhanced with
      gadolinium-DTPA. The tumors had diameters of 14 to 28 mm and were treated with a
      marginal dose of 14 to 17 Gy (mean 15.7 Gy). In the mean follow-up period of 27
      months after radiosurgery, all of the tumors decreased in size (PR).
      Neurologically, none of the patients showed any deterioration, and one
      demonstrated an obvious improvement in ocular movement. CONCLUSIONS: Radiosurgery
      for cavernous hemangioma in the cavernous sinus is apparently safe and effective
      with consistent tumor shrinkage. Therefore, radiosurgery is an excellent
      alternative to operative intervention and may even replace operative procedures
      if the tumors are small in diameter or when they recur.

PMID- 11580954
TI  - Anteposition of the internal carotid artery for surgical treatment of kinking.
AB  - BACKGROUND: Kinking of the extracranial portion of the internal carotid artery
      (ICA) requires surgical reconstruction when it causes neurological symptoms. We
      suggest a simple surgical reconstruction without arteriotomy. METHOD:
      Anteposition of the ICA ventral to the digastric muscle has been performed in
      three patients. Kinks in the ICAs, proved by angiography, were thought to be
      responsible for clinical signs and symptoms. RESULTS: The operations resulted in
      improvement, both clinically and radiologically. CONCLUSION: The complications of
      arteriotomy can be avoided using the technique of ICA antepositioning described
      in this paper.

PMID- 11580955
TI  - A giant internal carotid-posterior communicating artery aneurysm presenting with
      atypical trigeminal neuralgia and facial nerve palsy in a patient with autosomal
      dominant polycystic kidney disease: a case report.
AB  - BACKGROUND: In cases of internal carotid-posterior communicating artery (IC-PC)
      aneurysm, involvement of the trigeminal nerve at its root is rare, and facial
      nerve palsy is even more unusual. CASE REPORT: A large, unruptured IC-PC aneurysm
      was detected in a 56-year-old man with autosomal dominant polycystic kidney
      disease (ADPKD), but surgery was not performed because of mild renal dysfunction.
      Two months later, a sudden, severe headache suggested a subarachnoid hemorrhage,
      which was ruled out by computed tomography and lumbar puncture. Neurological
      examination revealed complete oculomotor palsy, atypical trigeminal neuralgia,
      and facial palsy with gustatory disturbance. Magnetic resonance (MR) imaging
      revealed a partially thrombosed giant aneurysm that directly compressed the
      trigeminal nerve root, reached the internal auditory canal, and was adjacent to
      the facial nerve. The neck of the aneurysm was successfully clipped via a
      subtemporal transtentorial approach. The postoperative course was uneventful, and
      all neurological symptoms had resolved within 3 months. CONCLUSIONS: We believe
      that the prosopalgia in this case was atypical trigeminal neuralgia due to direct
      compression of the trigeminal nerve root by the aneurysmal sac. A contributory
      cause was stretching of the oculomotor nerve, which contains sensory afferent
      inhibitory fibers derived from the ophthalmic branch of the trigeminal nerve. The
      facial palsy was of peripheral type and was accompanied by gustatory disturbance.
      This is the first reported case of facial palsy caused by an IC-PC aneurysm and
      also a very rare case of an IC-PC aneurysm clipped by a subtemporal
      transtentorial approach.

PMID- 11580958
TI  - An intraoperative irrigation device using disposable syringes and an extension
      tube: technical note.
AB  - BACKGROUND: The authors present a simple irrigation device used in a
      microsurgical setting. METHODS: The system consists of a disposable i.v.
      catheter, an extension tube, a three-way stopcock and two disposable syringes,
      capable of assembly during a surgical procedure. RESULTS: The length of the
      handpiece of this device is comparable to other microsurgical tools, which allow
      both the assistant and the surgeon to grab and irrigate in a coordinated fashion.
      Clots, tumor contents, and tissue debris are effectively washed away. This tool
      is particularly useful for lavage of subarachnoid clots during surgery for
      ruptured intracranial aneurysms, allowing precise anatomic orientation. This
      device is also practical for cooling tissues adjacent to drilling sites.
      CONCLUSION: This system is as efficacious as other available self-irrigating
      microneurosurgical instruments.

PMID- 11580960
TI  - Why U.S. neurosurgeons are in trouble: competition, cost containment, and caring.

PMID- 11580962
TI  - Diabetes healthcare strategies.
AB  - This article describes and contrasts two approaches to planning strategies for
      diabetes care. These are the 'epidemiologically based healthcare needs
      assessment' and 'marginal analysis'. Both have their advantages and
      disadvantages. The most effective way of planning services is likely to be a
      pragmatic combination of these two approaches.

PMID- 11580963
TI  - The role of cost-effectiveness analysis and health insurance in diabetes care.
AB  - The theme of World Diabetes Day for 1999 is 'The Costs of Diabetes'. This theme
      was chosen quite purposely to reflect the broad nature in which diabetes affects
      individuals, families, and society. For the theme can highlight the importance of
      diabetes from a medical, social, or economic perspective. This presentation
      addresses two issues, cost-effectiveness analysis and financial barriers to care,
      that pertain to the economic viewpoint. Economically, the costs of diabetes are
      varied. They include items that one can easily recognize, such as the
      expenditures related to medical treatment for diabetes (direct costs) or the
      earnings lost to individuals prematurely disabled or dying young (indirect
      costs). Other less well known costs exists as well. These include the opportunity
      costs to individuals with diabetes who forego other 'opportunities in life'
      because they made a decision to devote their financial or time resources to
      diabetes care. They also include costs to society, such as the impact of using
      existing resources in diabetes care unwisely, or having inappropriate priorities.
      Cost-effectiveness analyses in diabetes care address this last point. Health
      insurance issues highlight one aspect of opportunity costs in diabetes care.

PMID- 11580964
TI  - The cost of diabetes and diabetes care.
AB  - The number of people with diabetes mellitus worldwide is estimated to be 221
      million in 2010 compared to about 124 million in 1997. The dominant part of
      diabetic persons was in 1997 represented by Type 2 (97%). WHO expect the number
      of adults (20 years and older) with diabetes (i.e. a mix of Type 1 and 2) to rise
      to 300 millions in 2025 from 135 millions in year 1995. On average people with
      diabetes are three times more likely to be hospitalized than non-diabetic
      individuals. The risk for hospitalization is slightly diversified, venous
      complications being the least risky (1.7 times) and heart-related complications
      the most risky (3.1 times). The risk of premature death is higher for persons
      with diabetes compared to those without diabetes, and the life time expectancy is
      10-15 times shorter. US data shows that diabetes is the leading cause of
      blindness and accounts for 40% of the new cases of end-stage renal disease. The
      risk for leg amputation is 15-40 times higher and the risk for heart disease and
      stroke is two to four times higher for people with diabetes compared with people
      without diabetes. Recent studies show that the health care expenditures are as
      much as five times higher for individuals with diabetes compared to individuals
      without diabetes. In Sweden in 1994, three times more resources were spent on
      treating complications compared to what was spent on control of the disease.
      Studies show that intensive treatments cost more than traditional treatment, but
      also cut costs substantially for the treatment of late complications. The main
      message was that early intervention and intensified treatment had a better effect
      on the late complications. The basic message is quite simple: diagnose more
      persons with diabetes earlier, introduce and improve treatment.

PMID- 11580966
TI  - Epidemiology of type 2 diabetes in Taiwan.
AB  - In the face of the growing worldwide prevalence of type 2 diabetes, effective
      methods of preventing further increases in prevalence are needed. In this paper,
      we review the community-based epidemiologic studies of diabetes in Taiwan
      published during the last decade, and look at the effectiveness of a two-stage
      screening protocol for identifying subjects at risk for progression to type 2
      diabetes. The results of these studies indicate that the age-adjusted prevalence
      rate of undiagnosed diabetes in Taiwan is stable, at around 4.0%, while the
      annual incidence rate is about 1.8%. The results of several studies strongly
      suggest that a two-step screening strategy, in which only subjects with a fasting
      plasma glucose level of 5.6-7.8 mmol/l receive the oral glucose tolerance test,
      may be an effective means of identifying diabetics and persons at high risk for
      progression to type 2 diabetes and, ultimately, slowing the increase in the
      prevalence of this disease.

PMID- 11580965
TI  - Diabetes mellitus--a special medical challenge from a Chinese perspective.
AB  - As we enter the new millennium, Asia is being hit by an epidemic of diabetes and
      its related diseases. The rising prevalence of young onset diabetes which is
      closely associated with obesity and genetic factors as well as the increased
      propensity to develop kidney disease are special challenges in the management of
      Chinese diabetic patients. Although diabetic patients have earlier mortality and
      increased risks for micro and macrovascular complications, there is strong
      evidence that these devastating complications can be largely prevented by patient
      education, periodic assessments and use of appropriate therapeutic agents to
      optimize metabolic control and improve cardiovascular risk factors. However, a
      multidisciplinary approach is often required to deliver these complex disease
      management protocols. Hence, it is not surprising that large scale studies often
      revealed substandard diabetes management in both the hospital and community
      settings. This is often due to a combination of factors such as non-adherence to
      recommended guidelines both by patients and doctors as well as the 'non-urgent'
      and 'silent nature' of diabetes and its complications. To minimize the impacts of
      diabetes on quality of life, society productivity and utilization of health care
      resources, concerted efforts between health care professionals and public bodies
      are urgently needed to increase awareness, improve standards of care and develop
      better diagnostics and treatment modalities.

PMID- 11580967
TI  - A computer simulation model for cost-effectiveness analysis of mass screening for
      Type 2 diabetes mellitus.
AB  - The cost-effectiveness analysis of mass screening for Type 2 diabetes mellitus
      (DM) was performed to elucidate whether, who and how often it should be conducted
      in Taiwan. A series of Markov process was developed to model the disease natural
      history of Type 2 DM. A hypothetical cohort with 30,000 residents aged over 30
      years in Taiwan was randomly assigned to three arms of screening regimes,
      biennial, five-yearly and the control group. A Monte Carlo computer simulation
      was performed to calculate effectiveness of two screening regimes compared with
      the control group. Direct costs and utilities were incorporated to each
      corresponding state to calculate the incremental costs per life-years gained and
      per quality-adjusted life-years (QALYs) for biennial and five-yearly screening
      regimes. The incremental costs for biennial screening regime were estimated at
      $26,750 per life-year gained, and $17,833 per QALY. The corresponding figures for
      five-yearly screening regime were $10,531 per life-year gained and $17,113 per
      QALY. The incremental costs per life-year gained and per QALY increase with age,
      ranging from $17,238 for aged 30-39 years to $54,700 for aged over 70 years and
      from $9193 to 36,467, respectively. In conclusion, mass screening for Type 2 DM,
      especially in younger subjects, with 5-year inter-screening interval is cost
      effective in Taiwan.

PMID- 11580968
TI  - Direct costs-of-illness of patients with diabetes mellitus in Taiwan.
AB  - The purpose of the present study was to examine the characteristics of healthcare
      costs for diabetic patients in Taiwan. The study analyzed claim data from the
      Bureau of National Health Insurance for the period from July 1997 to June 1998.
      There were 536159 documented diabetic patients who were treated within the
      universal healthcare system in Taiwan during this study period. The annual number
      of visits of these diabetic patients was 6.2% of the total outpatient visits of
      all patients due to all causes during the one-year study period. Diabetes-related
      problems were the causes of 25.2% of outpatient visits among diabetic patients,
      while 74.8% of visits were for causes unrelated to diabetes. The distribution of
      treatment for the diabetic patients was by oral hypoglycemic agents 88.3%,
      insulin only 6.9%, and a combination of insulin and oral agents 4.8%. Diabetic
      patients accounted for 4,724,711 hospital inpatient days during the study period,
      which was 22.1% of the total inpatient days in Taiwan. Of the inpatient
      admissions, 13.9% were for diabetes as the principal cause, 23.4% were for
      diabetes-related disease, and 62.7% were for causes unrelated to diabetes. The
      direct costs of healthcare for the documented diabetic patients was 11.5% of the
      total costs of healthcare in Taiwan, and was 4.3 times higher than the average
      costs of care for non-diabetic individuals.

PMID- 11580969
TI  - The impact of diabetes on economic costs in dialysis patients: experiences in
      Taiwan.
AB  - Diabetes mellitus carries a great burden on healthcare costs due to its growing
      population and high co-morbidity. This adverse effect sustains even when patients
      develop end-stage renal disease (ESRD). We here present data showing the effect
      of diabetes on economic costs in dialysis therapy in Taiwan. As of the end of
      1997, we have 22,027 ESRD patients with a prevalence and incidence rate of 1013
      and 253 per million populations, respectively. Diabetic nephropathy is the second
      most common cause of the underlying renal diseases, but accounts for 24.8% of the
      prevalent patients and 35.9% of the incident cases. The diabetic patients
      engendered 11.8% more expense for care of dialysis than the non-diabetic patients
      (US $26,988 vs. US $24,146 per patient-year). Higher inpatient cost mainly
      account for the difference. As compared to non-diabetic patients, the diabetic
      patients had 3.5 times more inpatients costs (US $1325 vs. US $4677 per patient
      year), and higher proportion of inpatient-to-annualized cost ratio (5.5 vs.
      17.3%) resulting from their more frequent hospitalization (0.59 vs. 1.13 times
      per patient-year) and longer hospital stay (6.7 vs. 18.9 days per patient-year).
      The major causes responsible for a more frequent hospitalization were
      cardiovascular disease, poorly controlled hyperglycemia, sepsis and failure of
      vascular access. The annualized costs for care of dialysis patients in Taiwan,
      including inpatient and outpatient costs, averaged US $25,576 per patient-year.
      This value is approximately half of that in most of the western countries and
      Japan. Thus, a more cost-effective way to achieve savings is to reduce the high
      incidence rate of dialysis population and to maximize the quality of dialysis
      treatment for avoiding hospitalization. Recent studies had shown that tight blood
      pressure control, intensive glycemic control, and use of angiotensin converting
      enzyme inhibitors in diabetic patients significantly reduced not only the rate of
      progressive renal failure, but also substantially reduced the cost of
      complications and led to higher cost effectiveness. Once diabetic patients reach
      stage of ESRD, an optimized pre-ESRD care and consideration of kidney
      transplantation are essential in terms of better patient survival and cost
      savings.

PMID- 11580970
TI  - The current state of diabetes management in Taiwan.
AB  - The aim of this study was to provide an overview of diabetes management and
      complication status in Taiwan. A cohort of 2446 patients (from 25 diabetic
      centers) with more than 12 months of diabetes management participated and data
      were collected by interviews and reviewing the medical records. Overall, 97% were
      diagnosed as type 2 diabetes, with a mean age (+/-S.D.) of 61.6+/-11.3 years,
      duration of diabetes of 10.3+/-7.3 years and age at onset of diabetes of 51.5+/
      11.8 years. Mean BMI was 25.1+/-3.6 kg/m(2) and about 50% had BMI>25 kg/m(2).
      Majority (75%) were treated with oral hypoglycemic agents (OHAs), 14% with
      insulin and 10% with combination of insulin and OHA. Mean HbA(1c) was 8.1+/-1.6%
      and 59% had HbA(1c) >7.4% (1% above the upper limit of normal range, 4.7-6.4%).
      Mean FBG was 9.0+/-3.3 mmol/l and 59% had FBG>7.8 mmol/l. Of all the patients who
      had screening for complications, cataract (38%), neuropathy (30%), proteinuria
      (17%) and stroke (6%) were the most frequently reported eye, feet, kidney and
      late complications. We conclude that the majority of patients involved in this
      study had unsatisfactory glycaemic control which may lead to diabetes
      complications.

PMID- 11580971
TI  - An initial assessment of the feasibility and effectiveness of implementing
      diabetes shared care system in Taiwan--some experiences from I-Lan County.
AB  - Diabetes is the fifth leading cause of death in Taiwan and the burden of
      suffering is still increasing. Building a comprehensive and efficient health care
      system is crucial to improve the outcome of the diabetics. We implemented the
      first diabetes shared care system of Taiwan in I-Lan County since August 1996
      under the support of Department of Health, the Executive Yuan. This county-wide
      system was named 'Lan-Yang Diabetes Shared Care System' by the regional steering
      committee. Regional guidelines for diabetes management were developed after
      extensive discussion. A multidisciplinary diabetes care team was organized
      through a training and certification process. Registered patients held diabetes
      passports to keep clinical record. Physicians of the system use shared referral
      protocols and sheets. By the end of June 1999, 99 medical professionals had
      completed their training for diabetes shared care and been certified. The shared
      care system awarded 26 clinics to hang the lamp signs with the system logo to
      make them distinguishable. Such clinics have now been available throughout 12
      townships in I-Lan County. The number of registered patients carrying diabetes
      passport increased to 3484 and there was a community-based patient group in every
      township of I-Lan County. The amount of continuing diabetes clinical training
      delivered by the specialists to the primary care physicians and non-physician
      professionals increased to 1681 person-hours per year. The proportion of
      registered patients undertaking fundus examination within 1 year increased to
      30.9%, checking urine micro-albumin to 28.0% and checking HbA(1c) 72.8%,
      respectively. Mean HbA(1c) value decreased from 8.7% in the first year to 7.9% in
      the third year. Our study showed that under the co-ordination by regional health
      bureau with integration of different levels of medical facilities, governmental
      sectors and non-governmental community resources, the diabetes shared care model
      is feasible in Taiwan. Through its implementation, quality of regional diabetes
      care has achieved preliminary improvement.

PMID- 11580972
TI  - Tachyzoite-specific isoform of Toxoplasma gondii lactate dehydrogenase is the
      target antigen of a murine CD4(+) T-cell clone.
AB  - In two-dimensionally separated Toxoplasma gondii lysate, mouse Th1 clone 3Tx15
      detects two proteins of apparent molecular weight 40000 and pI of 5.8 and 5.9.
      Microsequencing of peptide fragments from tryptic digestion of one of these
      proteins yielded partial sequences of T. gondii lactate dehydrogenase (LDH)1. As
      shown by Western blot, toxoplasmic LDH co-migrates in two-dimensional gel
      electrophoresis with both T-cell antigenic proteins. With synthetic peptides
      spanning the complete primary structure of T. gondii LDH1, the T-cell epitope was
      mapped to a nine amino acid partial sequence which exhibits a motif for binding
      to I-E(k), the class II restriction element of antigen recognition by clone
      3Tx15. From the two known isoforms of T. gondii LDH, clone 3Tx15 specifically
      recognises tachyzoite LDH1, but not bradyzoite LDH2, as shown with the
      corresponding epitope peptides and recombinant proteins. Antigen-presenting cells
      infected with live bradyzoites stimulate 3Tx15 T cells, while killed bradyzoites
      provide no antigenic stimulus. This finding implies that a transformation into
      the tachyzoite stage occurs in cells challenged with bradyzoites. Although LDH1
      represents one major constituent of the tachyzoite proteome, the protein does not
      seem to be immunogenic in T. gondii infection of mice. This is evident from the
      lack of serum anti-LDH immunoreactivity and the failure of adoptively transferred
      3Tx15 T cells to protect against lethal challenge. In conclusion, a T-cell
      stimulatory Toxoplasma antigen is identified by means of a novel, high-resolution
      T-cell blot technique, the clones antigenic fine specificity allowing detection
      of parasite-stage conversion.

PMID- 11580973
TI  - A (1-->3)-beta-D-linked heptasaccharide is the unit ligand for glucan pattern
      recognition receptors on human monocytes.
AB  - Glucans are fungal cell wall polysaccharides which stimulate innate immune
      responses. We determined the minimum unit ligand that would bind to glucan
      receptors on human U937 cells using laminarin-derived pentaose, hexaose, and
      heptaose glucan polymers. When U937 membranes were pretreated with the
      oligosaccharides and passed over a glucan surface, only the heptasaccharide
      inhibited the interaction of glucan with membrane receptors at a K(d) of 31
      microM (95% CI 20-48 microM) and 100% inhibition. However, the glucan
      heptasaccharide did not stimulate U937 monocyte NFkappaB signaling, nor did it
      increase survival in a murine model of polymicrobial sepsis. Laminarin, a larger
      and more complex glucan polymer (M(w) = 7700 g/mol), only partially inhibited
      binding (61 +/- 4%) at a K(d) of 2.6 microM (99% CI 1.7-4.2 microM) with
      characteristics of a single binding site. These results indicate that a
      heptasaccharide is the smallest unit ligand recognized by macrophage glucan
      receptors. The data also indicate the presence of at least two glucan-binding
      sites on U937 cells and that the binding sites on human monocyte/macrophages can
      discriminate between glucan polymers. The heptasaccharide and laminarin were
      receptor antagonists, but they were not receptor agonists with respect to
      activation of NFkappaB-dependent signaling pathways or protection against
      experimental sepsis.

PMID- 11580974
TI  - Analysis of Borrelia burgdorferi gene expression during life cycle phases of the
      tick vector Ixodes scapularis.
AB  - Borrelia burgdorferi exists in nature via an enzootic cycle whereby the organism
      must adapt to the diverse environmental conditions provided inside the arthropod
      transmission vector and the mammalian reservoir hosts. B. burgdorferi genes shown
      to be regulated by temperature, pH and/or cell density during the organism's
      growth in culture medium were assayed for expression during various stages of the
      tick feeding cycle by reverse transcription-polymerase chain reaction (RT-PCR).
      ospA, ospC, flaB, erpA/I/N, erpB/J/O, rev and mlpA, were transcriptionally active
      following the larval and nymphal stages of feeding as determined by qualitative
      RT-PCR. During tick resting periods between feedings, ospC, mlpA and rev
      transcription were undetectable, in contrast to ospA, flaB, erpA/I/N and
      erpB/J/O. bba64, a gene induced by environmental changes in culture and expressed
      during mammalian infection, was not detectable during any of the tick life cycle
      phases. Quantitative PCR to determine B. burgdorferi genome equivalents in these
      tick samples using DNA co-purified with the RNA allowed an estimation of gene
      expression relative to the numbers of B. burgdorferi present in the ticks.
      Although the spirochete totals varied widely between individual tick pools of
      fed, replete nymphs, the relative expression ratios between individual target
      genes following a nymphal feed were comparable. Similarly, borrelial gene
      transcription from the larval feeding and the nymphal feeding were observed and
      compared. These findings analogize B. burgdorferi gene expression observed by
      environmental stimuli in vitro with the transcriptional activity occurring during
      the organism's infectious cycle within the tick.

PMID- 11580976
TI  - Microarrays for studying the host transcriptional response to microbial infection
      and for the identification of host drug targets.
AB  - It is essential to understand the molecular basis of a host's response to
      microbial infection so that disease and tissue damage can be prevented.
      Modulation of host RNA expression is a critical set of molecular changes that
      occur upon infection. Global analysis of gene expression should provide an
      understanding of host RNA transcriptional changes that occur upon host-pathogen
      interaction. This series of articles focuses on the use of microarrays for
      analyzing the transcriptional response of a host to microbial infection and for
      drug target identification.

PMID- 11580977
TI  - Gene expression data analysis.
AB  - Microarrays are one of the latest breakthroughs in experimental molecular
      biology, which allow monitoring of gene expression for tens of thousands of genes
      in parallel and are already producing huge amounts of valuable data. Analysis and
      handling of such data is becoming one of the major bottlenecks in the utilization
      of the technology. The raw microarray data are images, which have to be
      transformed into gene expression matrices, tables where rows represent genes,
      columns represent various samples such as tissues or experimental conditions, and
      numbers in each cell characterize the expression level of the particular gene in
      the particular sample. These matrices have to be analyzed further if any
      knowledge about the underlying biological processes is to be extracted. In this
      paper we concentrate on discussing bioinformatics methods used for such analysis.
      We briefly discuss supervised and unsupervised data analysis and its
      applications, such as predicting gene function classes and cancer classification
      as well as some possible future directions.

PMID- 11580978
TI  - Proteome analysis of bacterial pathogens.
AB  - Combining two-dimensional electrophoresis with mass spectrometry resulted in a
      powerful technology ideally suited to recognize and identify proteins of
      pathogenic microorganisms. This classical proteome analysis is now complemented
      by capillary chromatography/mass spectrometry combinations, miniaturization by
      chip technology and protein interaction investigations. Comparative proteomics is
      used to reveal vaccine candidates and pathogenicity factors. Immunoproteomics
      identifies specific and nonspecific antigens. For the management of the huge data
      amounts, bioinformatics is a valuable instrument for the construction of complex
      protein databases.

PMID- 11580979
TI  - Dynamics of host-parasite interactions: the example of population biology of the
      liver fluke (Fasciola hepatica).
AB  - Knowledge of the population dynamics of parasites and their hosts is essential to
      build veterinary and health programs. The example chosen is that of Fasciola
      hepatica, a food-borne trematode responsible for severe human and animal
      infections on the five continents. In this paper, we review the relationships
      between the liver fluke and its intermediate (mollusc) and definitive
      (vertebrate) hosts.

PMID- 11580980
TI  - Immunosenescence and infectious diseases.
AB  - Infectious diseases are major causes, with malignancies, of morbidity and
      mortality in the elderly. Increased susceptibility to infections may result from
      underlying dysfunction of an aged immune system; moreover, inappropriate
      immunologic functions associated with aging can determine an insufficient
      response to vaccines. Impairments of cellular, humoral and innate immunity in the
      elderly, contributing to increased incidence of infectious diseases, are
      discussed in this review.

PMID- 11580981
TI  - Modulation of apoptosis during herpes simplex virus infection in human cells.
AB  - Human herpes simplex virus (HSV) is cytolytic and has profound impacts on its
      host cells. Consequences of HSV infection include the induction of apoptosis and
      the concomitant synthesis of proteins which act to block this process. We review
      recent evidence showing how this important human pathogen modulates the
      fundamental cell death process.

PMID- 11580982
TI  - Microparticle vaccine approaches to stimulate mucosal immunisation.
AB  - Entrapment of antigens in biodegradable particles for mucosal immunisation has
      given successful outcomes in animals, but not as yet in man. Formulations using
      genuinely stable biocompatible nanoparticles with co-entrapped mucosal adjuvants
      and/or with surface-conjugated human M-cell-targeting ligands may lead to better
      uptake of intact antigen by Peyer's patch M cells and delivery to antigen
      presenting cells.

PMID- 11580983
TI  - Chlamydia pneumoniae-infected monocytes exhibit increased adherence to human
      aortic endothelial cells.
AB  - Interactions between monocytes and endothelial cells play an important role in
      the pathogenesis of atherosclerosis, and monocyte adhesion to arterial
      endothelium is one of the earliest events in atherogenesis. Work presented in
      this study examined human monocyte adherence to primary human aortic endothelial
      cells following monocyte infection with Chlamydia pneumoniae, an intracellular
      pathogen associated with atherosclerosis by a variety of sero-epidemiological,
      pathological and functional studies. Infected monocytes exhibited enhanced
      adhesion to aortic endothelial cells in a time- and dose-dependent manner. Pre
      treatment of C. pneumoniae with heat did not effect the organism's capacity to
      enhance monocyte adhesion, suggesting that heat-stable chlamydial antigens such
      as chlamydial lipopolysaccharide (cLPS) mediated monocyte adherence. Indeed,
      treatment of monocytes with cLPS was sufficient to increase monocyte adherence to
      endothelial cells, and increased adherence of infected or cLPS-treated monocytes
      could be inhibited by the LPS antagonist lipid X. Moreover, C. pneumoniae-induced
      adherence could be inhibited by incubating monocytes with a mAb specific to the
      human beta 2-integrin chain, suggesting that enhanced adherence resulted from
      increased expression of these adhesion molecules. These data show that C.
      pneumoniae can enhance the capacity of monocytes to adhere to primary human
      aortic endothelial cells. The enhanced adherence exhibited by infected monocytes
      may increase monocyte residence time in vascular sites with reduced wall shear
      stress and promote entry of infected cells into lesion-prone locations.

PMID- 11580984
TI  - Prevalence of CD8(+)alpha beta T cells in Trypanosoma cruzi-elicited myocarditis
      is associated with acquisition of CD62L(Low)LFA-1(High)VLA-4(High) activation
      phenotype and expression of IFN-gamma-inducible adhesion and chemoattractant
      molecules.
AB  - The determinants of the prevalence of CD8(+) T cells in the inflamed myocardium
      of Trypanosoma cruzi-infected patients and experimental animals are undefined.
      Using C3H/He mice infected with the Colombiana strain of T. cruzi, we found that
      the distribution of CD4(+)/CD8(-) and CD4(-)/CD8(+) T cells in the myocardium
      mirrors the frequency of cells expressing the CD62L(Low)LFA-1(High)VLA-4(High)
      activation phenotype among CD4(+)/CD8(-) and CD4(-)/CD8(+ )peripheral blood T
      cells. Consistently, vascular cell adhesion molecule-1-positive endothelial cells
      and a fine fibronectin network surrounding VLA-4(+) mononuclear cells were found
      in the inflamed myocardium. Further, interferon gamma (IFN-gamma) and IFN-gamma
      induced chemokines (RANTES, MIG and CRG-2/IP-10), as well as JE/MCP-1 and MIP1
      alpha, were found to be the dominant cytokines expressed in situ during acute and
      chronic myocarditis elicited by T. cruzi. In contrast, interleukin 4 mRNA was
      only detected during the chronic phase. Altogether, the results indicate that the
      distribution of T-cell subsets in the myocardium of T. cruzi-infected mice
      reflects the particular profile of adhesion molecules acquired by most peripheral
      CD8(+) T lymphocytes and point to the possibility that multiple IFN-gamma
      inducible molecules present in the inflamed tissue contribute to the
      establishment and maintenance of T. cruzi-induced myocarditis.

PMID- 11580985
TI  - Pseudomonas fluorescens as a potential pathogen: adherence to nerve cells.
AB  - In order to determine the infectious potential of the psychrotrophic bacterium
      Pseudomonas fluorescens, a species closely related to the opportunistic pathogen
      P. aeruginosa, we investigated the binding activity of this bacterium on primary
      cultures of rat neonate cortical neurons and glial cells, adrenal paraneurons and
      NG108-15 neuroblastoma cells. Incubated at concentrations of 10(6) and 10(8)
      CFU/mL, P. fluorescens MF37 exhibited a high binding activity on neurons in the
      same range as that of P. aeruginosa PAO1. A significant, but lower, adherence of
      P. fluorescens was also detected on glial cells and adrenal paraneurons. In
      contrast, when P. fluorescens MF37 or P. aeruginosa PAO1 were incubated with
      neuroblastoma cells, no binding was observed. In neurons, the association of P.
      fluorescens with the plasma membrane occurred both on neurites and cell body.
      Leakage of the cytoplasmic content was frequently noted. Studies performed using
      the fluorescent probe Hoechst 33258 revealed that in 10% of neurons, P.
      fluorescens induced the appearance of densely stained clusters of DNA that was
      typical of an early step of apoptosis. In glial cells exposed to P. fluorescens,
      marked changes in the morphology of the nucleus, including fragmentation into
      lobular structures and aggregation of DNA, were also reminiscent of the existence
      of a possible apoptotic mechanism. Taken together, these results reveal that P.
      fluorescens can bind to nerve cells and affect their physiology and, in agreement
      with recent clinical observations, suggest that P. fluorescens could behave as a
      pathogen.

PMID- 11580986
TI  - Protective humoral immunity induced by surface-associated material from
      Actinobacillus actinomycetemcomitans in mice.
AB  - The aim of the present study was to determine the role of antibodies specific to
      anti-surface-associated material from Actinobacillus actinomycetemcomitans (anti
      SAM-Aa) in an infection induced by this periodontopathogen in mice. When SAM-Aa
      obtained by saline extraction of A. actinomycetemcomitans Y4 was separated on one
      dimensional gel electrophoresis, this constituent contained antigen fragments
      with molecular weights ranging from 14000 to 79000. Immunoblot analysis revealed
      that increased antigen dose/immunization resulted in increased numbers of antigen
      epitopes recognized by serum antibodies of the immunized mice. Rapid healing of
      the primary lesions and high levels of specific IgG antibodies after challenge
      with live A. actinomycetemcomitans were seen in the immunized mice, especially at
      the highest-dose level of 100 microg/immunization. Transfer of SAM-Aa-immunized,
      but not the SAM-Aa-immunized and adsorbed, serum prior to challenge with live
      bacteria led to rapid healing of the lesions in the recipient mice. Increased
      phagocytosis of A. actinomycetemcomitans by murine macrophages (RAW264.7 cells)
      was observed when this periodontopathogen was opsonized by the SAM-Aa-immunized,
      but not SAM-Aa-immunized and adsorbed, serum. These results suggest that in mice,
      SAM-Aa antigens may induce protective antibodies by acting, at least, as an
      opsonin against challenge with live A. actinomycetemcomitans.

PMID- 11580987
TI  - Human cytomegalovirus infection of bone marrow myofibroblasts enhances myeloid
      progenitor adhesion and elicits viral transmission.
AB  - Human cytomegalovirus (CMV) infection of bone marrow transplant recipients can
      cause pancytopenia, as well as life-threatening interstitial pneumonia. CMV
      replicates actively in bone marrow stromal cells, whereas it remains latent in
      hematopoietic progenitors. Our aim was to study the influence of CMV infection on
      adherence of CD34(+) cells to the myofibroblastic component of human bone marrow
      and examine transmission of virus from myofibroblasts to CD34(+) cells. We show
      that smooth actin, but not fibronectin, organization is markedly modified by CMV
      infection of bone marrow stromal myofibroblasts. Nonetheless, CMV infection led
      to increased adherence of the CD34(+) progenitor cell line, KG1a, relative to
      adherence to uninfected myofibroblasts from the same donors. Adherence of CD34(+)
      cells to infected bone marrow myofibroblasts resulted in transfer of virions and
      viral proteins through close cell-to-cell contacts. This phenomenon may play a
      role in the pathophysiology of CMV bone marrow infection and in eventual virus
      dissemination.

PMID- 11580988
TI  - Intestinal microsporidiosis: a current infection in HIV-seropositive patients in
      Portugal.
AB  - Intestinal microsporidiosis is recognised as an important cause of opportunistic
      infections in immunocompromised patients, especially those with AIDS. Two species
      are implicated in diarrhoea and other gastrointestinal disease in HIV-infected
      patients: Enterocytozoon bieneusi and Encephalitozoon intestinalis. Diagnosis of
      gastrointestinal microsporidiosis was made by detecting spores of the parasite in
      stool specimens with Weber's modified trichrome stain and with some optical
      brightening agents such as UVITEX 2B or calcofluor white M2R. The identification
      of microsporidiosis at the species level was made using appropriate primers with
      PCR. The diagnosis of intestinal microsporidiosis is currently performed in the
      parasitology laboratory. In a study of 215 HIV-infected patients, conducted from
      1996 to 1999 (approximately n = 60/year), we found a prevalence of spores of
      microsporidia of 51.5% (n = 31) in 1996, 14.0% (n = 5) in 1997 and 12.5% (n = 8)
      in 1998 and 42.8% (n = 25) in 1999. Using PCR we found that E. intestinalis was
      the only species responsible for the gastrointestinal symptoms in 49 patients
      with microsporidian spores (71%) and E. bieneusi in 29% (n = 20).

PMID- 11580989
TI  - IgA responses in the intestinal mucosa against pathogenic and non-pathogenic
      microorganisms.
AB  - IgA is the most abundant immunoglobulin produced in mammals; most is secreted as
      a dimer across mucous membranes. This review discusses the different mechanisms
      of induction of IgA, and its role in protecting mucosal surfaces against
      pathogenic and non-pathogenic microorganisms.

PMID- 11580990
TI  - Rats, cats, people and parasites: the impact of latent toxoplasmosis on
      behaviour.
AB  - The manipulation hypothesis states a parasite may alter host behaviour for its
      own benefit, often by enhancing its transmission rate through the food chain.
      This paper reviews studies on the potential impact of one parasite, Toxoplasma
      gondii, on host behaviour, both on rodents, where altered responses may be
      proposed to benefit the parasite, and humans, where altered responses may arise
      as a side-effect of infection with no current adaptive significance.

PMID- 11580991
TI  - A psycho-endocrinological overview of transsexualism.
AB  - The technical possibility of surgical sex change has opened up a debate
      concerning the legitimacy and utility of carrying out such an intervention at the
      request of the transsexual. Diagnostic, psychological, medical and ethical
      arguments have been brought forth, both for and against. Nonetheless, anatomical
      transformation by surgical means has currently become a practice as the frequency
      of serious gender identity disorders is constantly progressing. After a brief
      introduction, the present paper will consider typological, aetiological and
      epidemiological aspects of transsexualism. Treatment of the sex change applicant
      is then defined and discussed in terms of psychological, psychiatric,
      endocrinological and surgical aspects. Finally, the question of post-operation
      follow-up will be examined.

PMID- 11580992
TI  - Longitudinal growth, sexual maturation and final height in patients with
      congenital hypothyroidism detected by neonatal screening.
AB  - OBJECTIVE: To evaluate longitudinal growth, pubertal development and final height
      in patients with congenital hypothyroidism (CH) detected by a neonatal screening
      programme, and to identify factors potentially affecting growth outcome.
      PATIENTS: Fifty-five patients (41 females) detected by neonatal screening and
      followed longitudinally from the time of diagnosis and treatment (25+/-5 days) up
      to the age of 17+/-0.5 years were evaluated retrospectively. RESULTS: Pubertal
      development began and progressed normally in both males and females. In boys, a
      testicular volume of 4 ml was reached at 11.3+/-1.0 years. In girls breast
      enlargement (B2) occurred at a mean age of 10.3+/-1.2 years and the mean age of
      menarche was 12.5+/-1.2 years. The onset and the progression of puberty were
      independent of the aetiology, the severity of CH and the timing of the beginning
      of treatment. Girls treated with an initial amount of L-thyroxine (L-T4) greater
      than 8 microg/kg per day showed an earlier onset of puberty (B2 9.4+/-0.9 years;
      menarche 11.5+/-0.8 years) compared with girls treated with a lower initial dose
      of L-T4 (B2 10.5+/-1.2 years; menarche 12.6+/-1.2 years; P<0.02). However, both
      groups attained a similar final height (-0.1+/-1.0 SDS and 0.4+/-1.0 SDS,
      respectively), which in both cases was above the target height (P=0.03). All the
      patients in the study attained a mean final height (0.1+/-1.1 SDS) within the
      normal range for the reference population and above the target height (-0.9+/-0.9
      SDS, P<0.0001). No significant relationship was found between final height and
      severity of CH at diagnosis, initial L-T4 dosage or aetiology of the defect.
      Patients with ectopic gland, thyroid aplasia or in situ gland attained a similar
      mean final height (0.1+/-1.1 SDS, 0.5+/-1.0 SDS and -0.5+/-1.0 SDS,
      respectively), which was in all cases greater than target height (-1.0+/-0.9, 
      0.6+/-0.8, -0.9+/-0.8 respectively; P<0.05). CONCLUSIONS: Our results suggest
      that conventional management of children with CH detected by neonatal screening
      leads to normal sexual development and normal adult height, and that the major
      factor determining height in these children is familial genetic growth potential.

PMID- 11580993
TI  - Polymorphism of the polyalanine tract of thyroid transcription factor-2 gene in
      patients with thyroid dysgenesis.
AB  - OBJECTIVE: One of the thyroid-specific transcription factors, thyroid
      transcription factor-2 (TTF-2), performs a crucial role in the development of the
      thyroid gland. We performed genetic analysis of the TITF2 gene (encoding TTF-2)
      in patients with thyroid dysgenesis. METHODS: By direct sequencing of the PCR
      products of TITF2, we screened the genomic DNA from 46 patients with thyroid
      dysgenesis (five had agenesis, six had hypoplasia, 15 had ectopy, and 20 were
      undetermined). We also studied the transcriptional activities of TITF2 by co
      expressing the luciferase gene directed by the human thyroglobulin gene promoter.
      RESULTS: Human TITF2 consists of a forkhead domain, a polyalanine tract, and
      unique C-terminal residues. In one of the patients with an ectopic sublingual
      thyroid, we found a polyalanine tract of 11 alanine residues on one chromosome
      instead of the 14 alanine residues found in normal controls. In one patient with
      hypoplasia, the polyalanine tract consisted of 12 heterozygous alanine residues.
      The reduced polyalanine tracts were not detected in 101 normal individuals.
      However, the expression study showed that the transcriptional activities of TITF2
      with reduced polyalanine-tract lengths were equal to that of TITF2 with an
      unreduced polyalanine tract. CONCLUSION: These results suggest that the
      polymorphism of the polyalanine tract of TITF2 is not a frequent cause of
      developmental defects of the human thyroid gland.

PMID- 11580994
TI  - Haemodynamic changes following treatment of subclinical and overt
      hyperthyroidism.
AB  - OBJECTIVE: Hyperthyroidism has profound effects on the cardiovascular system,
      including reduced systemic vascular resistance (SVR) due to relaxation of
      vascular smooth muscle cells, enhanced heart rate (HR) and cardiac output (CO)
      due to an increase in cardiac diastolic relaxation, contractility and heart rate.
      Subclinical hyperthyroidism is characterised by reduced serum TSH levels despite
      free thyroxine (T4) and tri-iodothyronine (T3) estimates within the reference
      range, in subjects with no obvious symptoms of hyperthyroidism. We measured
      haemodynamic changes (using impedance cardiography) in subjects with endogenous
      subclinical hyperthyroidism in order to elucidate whether these patients had
      signs of excess thyroid hormone at the tissue level. DESIGN: The patients were
      otherwise healthy women with a multinodular goitre (n=6; age 47-81 years; serum
      TSH 0.006-0.090 mU/l and normal free T4 and T3 estimates), studied before and
      after normalisation of TSH (0.280-1.120 mU/l) by means of radioiodine treatment,
      and they were compared with 9 overt hyperthyroid patients (2 with multinodular
      goitre and 7 with Graves' disease) in the untreated state and after euthyroidism
      had been obtained. RESULTS: Treatment of the subclinical hyperthyroid women
      resulted in 11% reduction in HR (P<0.02), 19% reduction in CO from (means+/-s.d.)
      6.93+/-2.15 l/min to 5.58+/-1.94 l/min (P<0.05), and 30% increase in SVR
      (P<0.02). Similar but more pronounced changes were seen in the hyperthyroid
      group: 17% reduction in HR, 25% reduction in CO and 46% increase in SVR (all at
      least P<0.05). Taking all 15 patients together, thyroid function (as measured by
      free T3 index (FT3I) or TSH) correlated significantly to the haemodynamic
      parameters as follows: the higher the thyroid function the lower the mean
      arterial pressure and SVR, and the higher the CO and central aortic compliance
      (stroke volume/pulse pressure) (P<0.05). Plasma norepinephrine increased
      significantly after treatment of the overt hyperthyroid patients, whereas
      epinephrine did not change, and no changes were seen among subclinical
      hyperthyroid patients. CONCLUSION: Treatment of endogenous subclinical
      hyperthyroidism resulted in significant changes in several haemodynamic
      parameters regarding the heart and the vascular system, compatible with some
      degree of excess tissue exposure to thyroid hormones in the untreated state. Our
      data favour more aggressive treatment of these patients, and endogenous
      subclinical hyperthyroidism might be regarded as a mild form of hyperthyroidism.

PMID- 11580995
TI  - Prevalence and characteristics of postpartum thyroid dysfunction in Tehran.
AB  - OBJECTIVE: To determine the prevalence of postpartum thyroiditis (PPT), one of
      the autoimmune disorders of the thyroid which usually occurs in women in the
      first year after parturition. PPT presents with periods of transient
      thyrotoxicosis and hypothyroidism, in many cases resulting in permanent
      hypothyroidism. DESIGN: The study involved 1040 mothers who had contacted five
      health centers in Tehran for vaccination of their children. METHODS: Signs and
      symptoms of hypothyroidism and thyrotoxicosis, and the presence of goiter (using
      the World Health Organization classification), were sought. Serum T3, T4, TSH,
      anti-TPO and anti-Tg antibodies were measured at 3, 4.5, 6 and 9 months after
      parturition. In those with hypothyroidism or thyrotoxicosis and a matched group
      of normal women, thyroid sonography was performed. RESULTS: The prevalence of
      thyroiditis was 11.4%. Hypothyroidism and thyrotoxicosis occurred in 68 and 42
      mothers respectively. Nine had thyrotoxicosis followed by hypothyroidism. There
      was one case of Graves' disease. Out of 68 hypothyroid patients, 33 women
      underwent treatment with levothyroxine (because of the severity of symptoms) for
      12 months. Six women showed increased TSH at 6 weeks after discontinuation of
      thyroxine. Stage II goiter (World Health Organization classification) were
      observed in 21.8% of patients and in 6.7% of pospartum euthyroid women (P<0.001).
      Positive anti-TPO was found in 61.5% of patients and in 19% of the control group;
      positive anti-Tg was found in 58% of patients and in 6% of the control group
      (P<0.001). Sonographic changes were observed in 96% of the patients and in 7% of
      the control group (P<0.001). There was no significant correlation between the
      occurrence of thyroiditis and parity, the age of the mother, a previous history
      of thyroid disease in the patient or family, breast-feeding, or the gender of the
      child. CONCLUSION: The results of this study show a high prevalence of PPT in
      Tehranian women. This may be due to the length and frequency of follow-up and/or
      the transition from low to adequate iodine intake. The major difference with
      respect to other studies is the low frequency of the biphasic form of PPT.

PMID- 11580996
TI  - Fas and Bcl-2 protein expression in thyrocytes of patients with nodular goiter.
AB  - OBJECTIVE: The relative expression of the apoptotic protein Fas and the anti
      apoptotic protein Bcl-2 were investigated in thyrocytes from patients with non
      toxic nodular goiter (NTG, n=20) and Hashimoto's thyroiditis (HT, n=5), who
      underwent fine-needle aspiration biopsy for diagnostic reasons. On the basis of
      the clinical and cytological findings, the patients with NTG were sub-classified
      into the group of those with colloid nodules (n=9), degenerative nodules (n=6)
      and adenomatous nodules (n=5). METHODS: Fine-needle biopsy aspirates were
      examined by immunocytochemistry for Fas and Bcl-2 expression, using specific
      monoclonal antibodies. For the evaluation of Fas and Bcl-2 immuno-reactivity, an
      expression index, based on the number of cells with positive staining, was used:
      grade 1 included samples with positive staining in <20% of cells; grade 2
      included samples with 20-50% positive cells; and grade 3 included samples with
      >50% positive cells. RESULTS: Fas protein expression was generally low (grade 1)
      in patients with nodular goiter, in contrast to patients with HT, in whom high
      expression was detected (grade 3). Only in aspirates from degenerative nodules
      (four out of six), and in which lymphocytes were also present, was Fas expressed
      at an intermediate level (grade 2). On the other hand, Bcl-2 protein was
      differentially expressed among the nodule subtypes. It was low in colloid and
      degenerative nodules (grade 1) but high in adenomatous ones (grades 2 and 3). Bcl
      2 expression was also low in patients with HT (grade 1). CONCLUSION: It is
      concluded that in comparison to HT, where there is up-regulation of Fas and down
      regulation of Bcl-2 protein, Fas expression is low in human goiter, indicating
      low apoptotic activity. The regulation of Bcl-2 protein differs between
      adenomatous and colloid nodules, suggesting that this protein may play a role in
      the differentiation of thyroid nodules.

PMID- 11580997
TI  - Detection of thyroglobulin mRNA transcripts in peripheral blood of individuals
      with and without thyroid glands: evidence for thyroglobulin expression by blood
      cells.
AB  - OBJECTIVE: Recent studies have assigned clinical significance and prognostic
      value to the detection of thyroglobulin (Tg) mRNA in the blood of patients
      subjected to total thyroidectomy for a papillary or follicular thyroid carcinoma.
      In this study, we investigated the diagnostic specificity of Tg mRNA detection,
      analysing blood samples from healthy volunteers and from patients previously
      subjected to total thyroidectomy for reasons other than a carcinoma of the
      follicular epithelium. DESIGN AND METHODS: Total RNA was extracted from whole
      blood, reverse-transcribed and the cDNA amplified for Tg and glyceraldehyde-3
      phosphate dehydrogenase with specific primers. Expression levels were analysed by
      using a semi-quantitative PCR. In a few cases, Lymphoprep gradients were used to
      separate the mononuclear and polymorphonuclear cells prior to further analysis by
      reverse transcription/PCR. RESULTS: Our data suggested that all individuals
      expressed Tg mRNA. Moreover, no differences in the expression levels between
      subjects with and without thyroid glands were documented. Documentation of Tg
      expression by the mononuclear and polymorphonuclear layers in patients without
      thyroid glands support the hypothesis that both lymphocytes and granulocytes
      express Tg and may justify a background expression in blood, independently of the
      presence of follicular cells in circulation. CONCLUSIONS: Tg mRNA expression is
      not limited to follicular cells of the thyroid gland, and its expression by
      normal blood cells should be considered in tests performed for diagnostic
      purposes.

PMID- 11580998
TI  - Homozygous inactivation of the MEN1 gene as a specific somatic event in a case of
      secondary hyperparathyroidism.
AB  - BACKGROUND: Most patients who have been surgically treated for secondary
      hyperparathyroidism (HPT) harbor at least one pathological parathyroid gland with
      a tumor of monoclonal origin. OBJECTIVE: To elucidate the underlying genetic
      mechanisms behind secondary HPT, by studying a panel of such tumors for numerical
      alterations. METHODS: Sixteen parathyroid glands from eight patients (median age
      58 years, range 31-74 years), were screened for numerical chromosomal imbalances,
      using comparative genomic hybridization (CGH). Mutation analysis of the multiple
      endocrine neoplasia type 1 gene (MEN1) was also performed by sequencing of the
      coding region. RESULTS: The results show that gross chromosomal alterations occur
      rarely in secondary HPT. In one of the three glands analyzed from one patient, a
      complete loss of chromosome 11 was detected. This gland also had an inactivating
      nonsense mutation, E469X, of the MEN1 gene. The mutation was present neither in
      the other two glands, nor in the constitutional tissue of the same patient, thus
      confirming its somatic origin. CONCLUSIONS: The relative lack of numerical
      chromosomal alterations would suggest that more discrete genetic alterations are
      responsible for the monoclonal growth in the majority of cases of secondary HPT.
      Furthermore, somatic inactivation of the MEN1 tumor suppressor gene contributes
      to the tumorigenesis in a small proportion of the cases.

PMID- 11580999
TI  - Frequency of the calcium-sensing receptor variant A986S in patients with primary
      hyperparathyroidism.
AB  - OBJECTIVE: Recent studies have shown an influence of the calcium-sensing receptor
      variant A986S on the serum calcium concentration, suggesting that this genetic
      variant could be a candidate for various bone and mineral disorders. The
      intention of this study was therefore to investigate the frequency of the
      described calcium-sensing receptor variants A986S, R990G and Q1011E in patients
      with primary hyperparathyroidism to test the hypothesis as to whether these
      variants represent risk factors for the development of primary
      hyperparathyroidism. DESIGN: Fifty patients with primary hyperparathyroidism were
      included in the study. One hundred and two healthy blood donors served as
      controls. METHODS: Detection of the genetic variants A986S, R990G and Q1011E was
      done by direct sequencing of exon 7 of the calcium-sensing receptor in leucocyte
      DNA. RESULTS: The heterozygous variant A986S was found in 34% (17 of 50) of the
      healthy age- and sex-matched controls and 40% (20 of 50) of the patients with
      primary hyperparathyroidism. This difference was not statistically significant
      (P=0.68). However, in male patients the heterozygous variant A986S was found more
      frequently (67%, 6 of 9) than in male controls (20%, 2 of 10, P=0.07). The
      variants R990G and Q1011E were found less frequently (8-20%) in patients and
      controls without significant differences between the groups. Patients with the
      heterozygous variant Q1011E had significantly higher serum calcium and
      parathyroid hormone levels than patients with the wild-type variant (P<0.01).
      There was no correlation of serum calcium (total and corrected for albumin) with
      the calcium sensing receptor variant A986S in 102 healthy blood donors (P=0.45).
      CONCLUSIONS: The calcium-sensing receptor variants do not, therefore, seem to be
      major genetic determinants for the development of primary hyperparathyroidism.
      The variant A986S may possibly represent a risk factor for the development of
      parathyroid neoplasia in men. Moreover, the presence of the genotype Q1011E might
      influence the clinical course of the disease. The previously reported significant
      correlation of serum calcium levels with the genetic variant A986S in healthy
      subjects could not be confirmed.

PMID- 11581000
TI  - Retrospective analysis of the association of nodular goiter with primary and
      secondary hyperparathyroidism.
AB  - BACKGROUND: The association of hyperparathyroidism (HPT) with thyroid disease has
      long been known, but the mechanisms underlying such an association have not yet
      been clarified. OBJECTIVE: To elucidate the main factors determining this
      combination of endocrine diseases, in a retrospective multicenter study. METHODS:
      We retrospectively reviewed all patients referred for parathyroid scintigraphy in
      the period 1990-1999. A total of 487 patients in the age range 17-65 years were
      selected for the analysis (339 women and 148 men); group A included 241 patients
      with primary and group B 246 patients with secondary HPT. RESULTS: A total of
      124/241 patients in group A (51.5%), but only 92/246 patients in group B (38.2%)
      had thyroid disorders (notably nodular goiter) associated with HPT (P=0.0035).
      Thyroid disorders were evenly distributed throughout the entire 17-65 years age
      range in group A, but 17-40-year-old patients in group B had significantly fewer
      thyroid disorders than the older patients of the same group (15.5% compared with
      43.3%, P<0.002), as expected in a general population. In patients with primary
      HPT there was no difference in the prevalence of thyroid disease between women
      and men, whereas the ratio of women to men in secondary HPT patients with thyroid
      disease was about 3:1. CONCLUSIONS: These results demonstrate an increased
      prevalence of nodular goiter in patients with primary rather than secondary HPT,
      and are consistent with a possible role of increased endogenous calcium
      concentrations (a hallmark of primary, but not of secondary, HPT) as a
      goitrogenic factor in patients with HPT.

PMID- 11581001
TI  - Urinary aquaporin-2 excretion in nocturnal enuresis.
AB  - OBJECTIVE: To evaluate the role of the arginine vasopressin (AVP)-aquaporin-2
      (AQP-2) axis in the pathogenesis of nocturnal enuresis. STUDY PARTICIPANTS:
      Twelve children (seven male and five female), aged 11.6+/-4.3 (6.7-15.6) years,
      suffering from primary monosymptomatic nocturnal enuresis and 12 healthy
      children, matched for sex and age. Enuretic children were further subdivided into
      responders and non-responders to treatment with 1-desamino-8-d-AVP (DDAVP).
      METHODS: Serum concentrations of AVP, and plasma and urine osmolality were
      measured at night (0100, 0400 and 0700 h), together with nocturnal urinary
      excretion of AQP-2 (2000-0800 h). Magnetic resonance imaging (MRI) of the
      pituitary gland was carried out to evaluate the amount of AVP stored in the
      posthypophysis. RESULTS: Mean AVP serum concentrations were similar in patients
      and controls. Urinary AQP-2 was also similar in patients and controls, but
      responders had a significantly lower level of AQP-2 than non-responders
      (P<0.005). Plasma osmolality was greater in patients than in controls (P<0.001),
      whereas urinary osmolality was similar in both groups. No difference in the ratio
      of the signal intensity of the posterior lobe of the hypophysis to that of the
      pons (AVP content) was found between patients and controls or between responders
      and non-responders. CONCLUSION: A decreased urinary excretion of AQP-2 is
      associated with, and seems to have a role in, nocturnal enuresis, at least in
      some children, and this could also explain why only some of them respond to DDAVP
      treatment.

PMID- 11581002
TI  - Autosomal dominant neurohypophyseal diabetes insipidus in a Swiss family, caused
      by a novel mutation (C59Delta/A60W) in the neurophysin moiety of prepro
      vasopressin-neurophysin II (AVP-NP II).
AB  - OBJECTIVE: To study clinical, morphological and molecular characteristics in a
      Swiss family with autosomal dominant familial neurohypophyseal diabetes insipidus
      (adFNDI). PARTICIPANTS AND METHODS: A 15-month-old girl presenting with symptoms
      of polydipsia and polyuria was investigated by water deprivation test. Evaluation
      of the family revealed three further family members with symptomatic vasopressin
      deficient diabetes insipidus. T1-weighted magnetic resonance images of the
      posterior pituitary were taken in two affected adult family members and molecular
      genetic analysis was performed in all affected individuals. RESULTS: The water
      deprivation test in the 15-month-old child confirmed the diagnosis of vasopressin
      deficient diabetes insipidus and the pedigree was consistent with autosomal
      dominant inheritance. The characteristic bright spot of the normal vasopressin
      containing neurophypophysis was absent in both adults with adFNDI. Direct
      sequence analysis revealed a new deletion (177-179DeltaCGC) in exon 2 of the AVP
      NP II gene in all affected individuals. At the amino acid level, this deletion
      eliminates cysteine 59 (C59Delta) and substitutes alanine 60 by tryptophan (A60W)
      in the AVP-NP II precursor; interestingly, the remainder of the reading frame
      remains unchanged. According to the three-dimensional structure of neurophysin,
      C59 is involved in a disulphide bond with C65. CONCLUSIONS: Deletion of C59 and
      substitution of A60W in the AVP-NP II precursor is predicted to disrupt one of
      the seven disulphide bridges required for correct folding of the neurophysin
      moiety and thus disturb the function of neurophysin as the vasopressin transport
      protein. These data are in line with the clinical and morphological findings in
      the reported family with adFNDI.

PMID- 11581003
TI  - Effect of hydration on exercise-induced growth hormone response.
AB  - DESIGN: Growth hormone (GH) has demonstrated water-retaining effects in subjects
      at rest, whereas other research has indicated that GH may stimulate sweating.
      Thus, the aim of this study was to investigate the effect of fluid intake on the
      exercise-induced GH response. METHODS: Seven healthy male volunteers (age: 27.4+/
      1.3 years, weight: 74.5+/-1.1 kg, height: 179.3+/-2.3 cm) performed a 40-min
      submaximal rectangular cycling exercise in two different sessions. The first
      session (Session 1) was performed without water intake, and the second (Session
      2) involved the ingestion of spring water (four intakes) corresponding to the
      volume of water lost during the first session. RESULTS: In session 1, the water
      loss was 568+/-32 ml. In Session 2, the volume of water loss was not
      significantly different from the volume of fluid intake (524+/-16 versus 568+/-32
      ml respectively). The decrease in plasma volume was significantly reduced in
      Session 2 (-6.69+/-1.59% versus -11.3+/-1.89%; P<0.05). In Session 1, the GH
      concentration was significantly lower than that during Session 2 after 25 min
      (3.04+/-1.05 versus 5.26+/-1.81; P<0.05) and after 40 min (13.7+/-3.55 versus
      17.60+/-4.14 ng/ml; P<0.05) of exercise. The total GH response was significantly
      lower in Session 1 than in Session 2 (136.6+/-39.2 versus 202.4+/-58.9 ng/ml x
      min; P<0.05). CONCLUSIONS: We conclude that the exercise-induced GH response
      decreases when exercise is performed without fluid intake.

PMID- 11581004
TI  - Successful treatment of resistant acromegaly with a growth hormone receptor
      antagonist.
AB  - BACKGROUND/OBJECTIVE: Pegvisomant is a pegylated analogue of human GH and
      functions as a potent GH receptor antagonist. This novel mode of action gives it
      the potential to achieve biochemical control in patients with acromegaly whose
      disease activity cannot be satisfactorily controlled by conventional therapy. We
      have documented the clinical details of seven patients with residual active
      acromegaly after surgery and/or radiation therapy successfully treated with
      pegvisomant. PATIENTS/METHODS: Seven patients (four male, mean age 47 years,
      range 34-67 years) who participated in two separate clinical trials of
      pegvisomant have completed 2 years (four patients) or 1 year (three patients) of
      treatment. All had active acromegaly (mean serum GH level >5 mU/l; serum IGF-I
      elevated for age) that could not be controlled with standard medical therapy
      (dopamine agonist and/or a somatostatin analogue) following appropriate primary
      treatment with surgery and/or radiotherapy. RESULTS: On a median dose of 20
      mg/day (range 15-40) pegvisomant, serum IGF-I fell from a mean of 920+/-351 ng/ml
      (s.d.) to 258+/-91 ng/ml and was normalised in all seven patients. These changes
      were associated with improvements in soft tissue enlargement and general well
      being. Treatment was well tolerated and no change in pituitary tumour size was
      evident on MRI scans performed every 6 months. CONCLUSIONS: Treatment with
      pegvisomant is safe and efficacy is maintained after 2 years. Serum IGF-I may be
      normalised in patients who are refractory to conventional therapy.

PMID- 11581006
TI  - Renal loss of leptin in patients with nephrotic syndrome.
AB  - OBJECTIVE: In humans, short term changes of serum leptin lead to alterations in
      food intake and energy expenditure. The objective of the present study was to
      relate urine leptin concentrations with the extent of proteinuria in patients
      with nephrotic syndrome (NS). A second goal was to investigate the impact of
      potential urinary leptin losses on serum leptin concentrations and body
      composition. DESIGN AND METHODS: Seventeen patients with proteinuria were
      compared with twenty patients with remission of NS and ten healthy children.
      Leptin was measured by radioimmunoassay. RESULTS: Urinary leptin excretion in
      proteinuric patients was significantly higher than in non-proteinuric patients
      with and without NS and in healthy controls (2.64+/-0.034 microg/g creatinine,
      0.026+/-0.05 microg/g creatinine, and 0.073+/-0.11 microg/g creatinine
      respectively; P<0.001 and P<0.01 respectively compared with controls). Urine
      leptin positively correlated with urine IgG concentration (P=0.013, r2=0.36) in
      the proteinuric group. No difference in serum leptin values could be demonstrated
      between the three groups. CONCLUSIONS: In summary, our data demonstrate a
      significant leptin excretion in children with severe proteinuria. Proteinuria,
      however, does not lead to changes in serum leptin, suggesting that the
      significant loss of leptin is compensated for by sustained up-regulation of
      leptin production.

PMID- 11581005
TI  - Metabolic effects of dehydroepiandrosterone replacement therapy in postmenopausal
      women.
AB  - OBJECTIVE: To investigate whether long-term treatment with dehydroepiandrosterone
      (DHEA) in postmenopausal women can modify insulin sensitivity and plasma lipid
      profile. DESIGN AND METHODS: Twenty healthy postmenopausal women with serum
      dehydroepiandrosterone sulfate (DHEA-S) concentrations <2.5 micromol/l were
      enrolled and randomly assigned to two different treatment groups: group 1 were
      treated with micronized DHEA, 25 mg/day at 0800 h for 12 months; group 2 were
      treated with an identical placebo tablet. At the beginning and at the end of the
      study, plasma lipid profile, glucose tolerance (oral glucose tolerance test) and
      insulin sensitivity (euglycemic hyperinsulinemic clamp: M index) were assessed.
      RESULTS: After 12 months, the group treated with DHEA showed a considerable
      improvement of insulin sensitivity (M index +29.55%, P=0.01) and lipid pattern
      (high-density lipoprotein cholesterol +11.61%, P=0.03; low-density lipoprotein
      cholesterol -11.07%, P=0.04; triglycerides -19.60%, P=0.03), but glucose
      tolerance did not change. No modifications were observed in the placebo group.
      CONCLUSIONS: Long-term treatment with DHEA ameliorates some metabolic parameters
      that are linked to increased cardiovascular risk and, consequently, this seems to
      be an interesting therapeutic tool in the management of the postmenopausal
      syndrome.

PMID- 11581007
TI  - Diagnosis of a patient with oncogenic osteomalacia using a phosphate uptake
      bioassay of serum and magnetic resonance imaging.
AB  - A previously healthy man with no family history of fractures presented with
      muscle pain, back pain and height loss. Investigations revealed
      hypophosphataemia, phosphaturia, undetectable serum 1,25-dihydroxyvitamin D and
      severe osteomalacia on bone biopsy, suggestive of a diagnosis of oncogenic
      osteomalacia. Thorough physical examination did not locate a tumour. Support for
      the diagnosis was obtained by detection of phosphate uptake inhibitory activity
      in a blinded sample of the patient's serum using a renal cell bioassay. On the
      basis of detection of this bioactivity, a total body magnetic resonance (MR)
      examination was performed. A small tumour was located in the right leg. Removal
      of the tumour resulted in the rapid reversal of symptoms and the abnormal
      biochemistry typical of oncogenic osteomalacia. Inhibitory activity was also
      demonstrated using the bioassay in serum from two other patients with confirmed
      or presumptive oncogenic osteomalacia, but not in serum from two patients with
      hypophosphataemia of other origin. This is the first case to be reported in which
      the diagnosis of oncogenic osteomalacia was assisted by demonstration of
      inhibitory activity of the patient's serum in a renal cell phosphate bioassay
      that provided an impetus for total body MR imaging.

PMID- 11581009
TI  - Genomic organization of the human thyroglobulin gene: the complete intron-exon
      structure.
AB  - OBJECTIVE: In order to complete the knowledge of the genomic organization of the
      human thyroglobulin gene, the present work was designed to establish the intron
      exon organization from exon 24 to exon 35 and to construct a more complete
      physical map of the gene. DESIGN: Screening of two genomic libraries, and
      subsequent restriction mapping, hybridization and sequencing were used to
      characterize the recombinant phages. METHODS: Two human genomic DNA libraries
      were screened by in situ hybridization. Southern blotting experiments were
      performed to characterize the phage inserts. The Long PCR method was used to
      amplify the genomic DNA region containing exon 24. Intron-exon junction sequences
      were determined by using the Taq polymerase-based chain termination method.
      RESULTS: We isolated and characterized five lambda phage clones that include
      nucleotides 4933 to 6262 of the thyroglobulin mRNA, encompassing exons 25-35 of
      the gene. The remaining exon 24 (nucleotides 4817-4932) was sequenced from the
      amplified fragment. In total, 8010 intronic bases were analyzed. CONCLUSIONS: The
      present study shows that the five phages isolated and the amplified fragment
      include 59.4 kb genomic DNA, covering 1446 nucleotides of exonic sequence
      distributed over 12 exons, from exon 24 to exon 35. Using previous studies and
      our current data, 220 kb of the human thyroglobulin gene was analyzed, a physical
      map was constructed, and all exon-intron junctions were sequenced and correlated
      with the different domains of the protein. In summary, the thyroglobulin gene
      contains 48 exons ranging in size from 63 nucleotides to 1101 nucleotides.

PMID- 11581008
TI  - Phosphoinositide 3-kinase inhibits megalin-mediated transcytosis of thyroglobulin
      across thyroid epithelial cells at a post-sorting level.
AB  - BACKGROUND: Phosphoinositide 3-kinase (PI3-K) is implicated in various cellular
      processes involving signaling, including intracellular trafficking. PI3-K has
      been shown to play a part in both receptor- and non-receptor-mediated
      transcytosis across cultured kidney cells and undifferentiated thyroid cells.
      OBJECTIVE: To investigate the role of PI3-K in transcytosis of thyroglobulin (Tg)
      across differentiated cultured Fisher rat thyroid cells (FRTL-5 cells) - a
      process known to be mediated by megalin, a member of the low-density lipoprotein
      receptor family. DESIGN: We studied the effect of the microbial product
      wortmannin, a specific inhibitor of PI3-K, on transcytosis of Tg across FRTL-5
      cells. METHODS: Transcytosis experiments were performed using FRTL-5 cells
      cultured as tight layers on filters in the upper chamber of dual chambered
      devices, with megalin expression exclusively on the upper cell surface. Tg was
      added to the upper chamber and cells were incubated at 37 degrees C. Transcytosed
      Tg was measured in fluids collected from the lower chamber. To study the role of
      PI3-K, cells were pre-incubated with wortmannin. RESULTS: Pre-incubation of FRTL
      5 cells with wortmannin did not affect Tg binding and uptake, but resulted in a
      considerable increase in Tg transcytosis (by 40-75%, depending on the
      concentration of wortmannin), suggesting that PI3-K exerts an inhibitory effect
      on Tg transcytosis. In experiments in which a monoclonal antibody against megalin
      was used to reduce Tg transcytosis, pre-incubation with wortmannin did not
      increase Tg transcytosis from its reduced levels, indicating that PI3-K is
      involved in the megalin-mediated pathway. Wortmannin did not affect the extent of
      release of tri-iodothyronine from exogenously added Tg by FRTL-5 cells, which was
      used as a measure of Tg degradation in the lysosomal pathway, indicating that the
      effect of PI3-K on transcytosis occurs after diversion of Tg from the lysosomal
      pathway. CONCLUSIONS: PI3-K exerts an inhibitory role on megalin-mediated Tg
      transcytosis across cultured thyroid cells. PI3-K action takes place at a post
      sorting level, after Tg bypassing of the lysosomal pathway.

PMID- 11581010
TI  - In vitro and in vivo herpetic vector-mediated gene transfer in the pituitary
      gland: impact on hormone secretion.
AB  - OBJECTIVE: Herpes simplex virus type 1 (HSV-1)-derived vectors are known to be
      effective tools to deliver transgenes into normal and neoplastic anterior
      pituitary (AP) cells in vitro. Our objective was to assess the in vitro and in
      vivo effects of tsK/beta-gal, a temperature-sensitive HSV-1-derived vector
      harbouring the E. coli beta-galactosidase gene, on AP hormone secretion as well
      as on transgene expression in rat AP tumours (hyperplastic prolactinomas).
      DESIGN: The impact of vector infection on prolactin (PRL) and GH release was
      determined in vitro in normal and hyperplastic (lactotrophic) dispersed AP cells
      exposed for 24 h to tsK/beta-gal as well as in vivo in ectopic AP grafts. In some
      oestrogen-induced prolactinoma-carrying rats, vector suspension was
      stereotaxically injected into the glands to assess transgene expression in vivo.
      METHODS: GH and PRL release was measured by specific RIAs. In vivo transgene
      expression was assessed by immunohistochemistry for beta-galactosidase and
      enzymohistochemistry (5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside).
      Ectopic pituitary grafts and stereotaxic surgery were performed following
      standard procedures. RESULTS: At a multiplicity of infection of 0.5, the vector
      induced a 30 and 22% fall in PRL and GH release respectively in normal AP cells,
      whereas the corresponding hormone release inhibition for hyperplastic AP cells
      was 41 and 33% for PRL and GH respectively. In ectopic pituitary grafts, the
      effect of vector infection on hormone secretion was assessed by measuring serum
      PRL levels in the host rats every 5 days for 4 weeks post-grafting. In the
      pituitary-grafted rats that received the viral vector, serum PRL failed to
      increase to the levels achieved in control-grafted animals. Finally, pituitary
      tumours stereotaxically injected with tsK/beta-gal showed widespread expression
      of the beta-galactosidase transgene around the injection areas. CONCLUSIONS: The
      results reported here have implications for basic studies using gene transfer to
      pituitary gland as well as potential gene therapy approaches to pituitary
      diseases.

PMID- 11581011
TI  - Effect of cytokines and growth factors on the secretion of inhibin A, activin A
      and follistatin by term placental villous trophoblasts in culture.
AB  - OBJECTIVE: Maternal serum inhibin A and activin A are higher in pre-eclampsia
      than in normal pregnancy. The placenta is a source of these proteins in
      pregnancy. The aim of this study was to investigate the effect of growth factors
      and proinflammatory cytokines that are raised in pre-eclampsia on the secretion
      of dimeric inhibin A, activin A and follistatin by villous cytotrophoblasts in
      culture. DESIGN AND METHODS: Villous cytotrophoblasts were prepared from term
      placentae and cultured in serum-free media. Cells were treated with increasing
      concentrations of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta,
      transforming growth factor (TGF)-beta1, granulocyte and monocyte colony
      stimulating factor (GMCSF), inhibin A, activin A and follistatin for 2 days.
      Culture supernatants were assayed for human chorionic gonadotrophin (hCG),
      inhibin A, activin A and follistatin as appropriate. Experiments were repeated at
      least three times with each cytokine or growth factor and the data pooled.
      RESULTS: Cytotrophoblasts syncytialise and spontaneously secrete hCG, inhibin A
      and activin A in culture. Follistatin levels were <20 pg/ml in most experiments.
      Activin A secretion was increased in culture in a dose-dependent manner by IL
      1beta (approximately 150%, P<0.05), TNF-alpha (approximately 35%, P=0.02) and
      GMCSF (approximately 100%, P<0.01). hCG secretion was inhibited in a dose
      dependent manner by TNF-alpha (50%, P<0.05). Inhibin A was stimulated by IL-1beta
      ( approximately 30%, P=0.05). Inhibin A, activin A, follistatin or TGF-beta1 did
      not have a significant effect on any measured parameters. CONCLUSIONS: These data
      show that inflammatory cytokines increase the secretion of activin A by
      trophoblasts in culture. The presence of very low levels, or no follistatin (<20
      pg/ml) in the culture media suggests 'free' activin A could have
      autocrine/paracrine effects on cytotrophoblasts. Inhibin A secretion was
      stimulated by IL-1beta. However, absence of an effect by the other cytokines
      investigated on inhibin A in this study suggests that the mechanism(s) involved
      in increasing maternal circulating levels of inhibin A and activin A in pre
      eclampsia are controlled differentially.

PMID- 11581012
TI  - Bisphenol-A, an environmental estrogen, activates the human orphan nuclear
      receptor, steroid and xenobiotic receptor-mediated transcription.
AB  - BACKGROUND: There is increasing concern about endocrine-disrupting chemicals
      (EDCs) which may produce adverse health effects in humans and other species. One
      such chemical, bisphenol-A (BPA), a monomer of polycarbonate plastics, is widely
      used in consumer products; it has been reported to contain estrogenic activity
      through binding to estrogen receptors. Cytochrome P450 mono-oxygenase 3A4
      (CYP3A4) is one of the key enzymes for the metabolism of endogenous steroids and
      foreign chemicals in liver. The orphan nuclear receptor, steroid and xenobiotic
      receptor (SXR/PXR), has recently been isolated. A variety of known inducers of
      CYP3A4 bind to SXR/PXR, and stimulate transcription on xenobiotic-response
      elements (XREs) located in the promoter region of the CYP3A4 gene. Recent study
      has shown that EDCs, diethylhexylphthalate (DEHP) and nonylphenol, but not BPA,
      induce mouse SXR/PXR-mediated transcription. However, it is known that species
      differences in SXR alter CYP3A inducibility. OBJECTIVE: To test whether BPA
      stimulates human SXR/PXR-mediated transcription using reporter gene assays.
      METHODS: Transfection assays were performed with human SXR/PXR expression plasmid
      and a reporter plasmid containing the XREs in the CYP3A4 gene promoter in HepG2
      cells. BPA-induced interaction of human SXR/PXR with steroid receptor coactivator
      1 (SRC-1) was analyzed by mammalian two-hybrid assays. RESULTS: BPA, as well as
      DEHP, activated human SXR-mediated transcription on the XREs. In mammalian two
      hybrid assays, BPA recruited SRC-1 to the ligand-binding domain of human SXR/PXR.
      CONCLUSIONS: Our observations have indicated that BPA may be a human-specific
      inducer of the CYP3A4 gene, and may influence the metabolism of endogenous
      steroids, drugs, and other xenobiotics.

PMID- 11581013
TI  - Mammary gland development and lactation are controlled by different
      glucocorticoid receptor activities.
AB  - OBJECTIVE: Regulation of physiological processes by glucocorticoids is achieved
      by binding to the glucocorticoid receptor (GR) and subsequent modulation of gene
      expression, either by DNA binding-dependent mechanisms or via protein-protein
      interaction with other transcription factors. The purpose of this study was to
      define the molecular mechanism of GR underlying the control of mammary gland
      development and lactation. DESIGN: To dissect the mechanism of GR action in the
      mammary gland, we used genetically modified mice carrying a DNA binding-defective
      GR. These mice retain the ability to regulate transcription by protein-protein
      interaction but fail to control gene expression by DNA binding-dependent
      mechanisms. Thus, they allow the study of the mode of GR action in vivo. METHODS:
      The development of the mammary gland and milk protein synthesis during lactation
      were studied using histological and biochemical methods. RESULTS: Our findings
      demonstrated that the lack of the DNA binding function of GR impairs the ductal
      development of the mammary gland in virgin females and that this can presumably
      be accounted for by reduced proliferation of epithelial cells. In contrast,
      lactating females have normally differentiated mammary glands and are fully
      capable of milk protein production. This is in good agreement with the
      demonstration that the DNA binding-defective GR is still able to interact with
      phosphorylated Stat5 proteins, suggesting that transcriptional regulation by
      protein-protein interaction forms the basis of glucocorticoid action in this
      process. CONCLUSIONS: The present study has demonstrated that GR plays an
      important role in the mammary gland and that it uses different molecular modes of
      action to control development and milk protein synthesis.

PMID- 11581014
TI  - Maternal glucocorticoid treatment modulates placental leptin and leptin receptor
      expression and materno-fetal leptin physiology during late pregnancy, and elicits
      hypertension associated with hyperleptinaemia in the early-growth-retarded adult
      offspring.
AB  - BACKGROUND: Leptin concentrations are increased during late pregnancy, and leptin
      receptors are expressed in placental and fetal tissues, suggesting a role for
      leptin in placental and/or fetal growth, or both. In humans, leptin
      concentrations in adulthood are inversely related to body weight at birth,
      independent of adult adiposity, and correlate with fasting insulin.
      Glucocorticoids and insulin regulate leptin secretion. Excessive exposure to
      glucocorticoids during late fetal development in the rat causes intrauterine
      growth retardation (IUGR), together with hypertension and hyperinsulinaemia in
      adulthood. Leptin may have a role in the development of some forms of
      hypertension. OBJECTIVE: To determine whether IUGR induced by maternal
      glucocorticoid treatment during the last third of pregnancy in the rat is
      associated with modulation of either maternal or fetal leptin concentrations, the
      placental expression of leptin or the short form of the leptin receptor (ObR-S),
      or combinations thereof, and to evaluate whether hypertension or
      hyperinsulinaemia in the early-growth-retarded adult progeny of dexamethasone
      treated dams is associated with altered leptin concentrations. DESIGN AND
      METHODS: Dexamethasone was administered to pregnant rats from day 15 to day 21 of
      gestation via a chronically implanted subcutaneous osmotic minipump. Protein
      expression of leptin and ObR-S in the placenta at day 21 of pregnancy was
      measured by western blotting. Plasma leptin and insulin concentrations were
      determined by radioimmunoassay and ELISA respectively. Systolic hypertension was
      measured by tail cuff plethysmography. RESULTS: Dexamethasone administration
      during the last third of pregnancy decreased placental mass and fetal body weight
      at day 21 of gestation, caused maternal hyperleptinaemia but fetal
      hypoleptinaemia, and suppressed placental leptin protein expression whilst up
      regulating placental protein expression of ObR-S. The male and female offspring
      of dexamethasone-treated dams were hypertensive from 12 weeks of age. One-year
      old offspring of dexamethasone-treated dams exhibited significant
      hyperleptinaemia compared with age-matched controls, an effect associated with
      hyperinsulinaemia in the male, but not female, offspring. CONCLUSIONS: The rat
      model of maternal dexamethasone treatment is established as a paradigm of
      'programmed' hypertension in man. Our data show modification of placental leptin
      and leptin receptor protein expression by dexamethasone treatment during the last
      third of pregnancy. We also show that leptin concentrations are suppressed during
      fetal life but increased in adulthood in this rat model of programmed
      hypertension. Our data do not necessarily establish a causal relationship between
      fetal hypoleptinaemia and impaired fetal growth during early life, or between
      hyperleptinaemia and hypertension in adulthood. Nevertheless, they suggest that
      hyperleptinaemia may be a component of the cluster of metabolic abnormalities
      seen in the insulin resistance syndrome in man. They also suggest that excessive
      fetal exposure to glucocorticoids could be a common early-life stimulus to the
      association between hyperinsulinaemia, hypertension and hyperleptinaemia often
      seen in individuals of low birthweight.

PMID- 11581015
TI  - Searching for A3243G mitochondrial DNA mutation in buccal mucosa in order to
      improve the screening of patients with mitochondrial diabetes.

PMID- 11581016
TI  - Time-series analysis of delta13C from tree rings. I. Time trends and
      autocorrelation.
AB  - Univariate time-series analyses were conducted on stable carbon isotope ratios
      obtained from tree-ring cellulose. We looked for the presence and structure of
      autocorrelation. Significant autocorrelation violates the statistical
      independence assumption and biases hypothesis tests. Its presence would indicate
      the existence of lagged physiological effects that persist for longer than the
      current year. We analyzed data from 28 trees (60-85 years old; mean = 73 years)
      of western white pine (Pinus monticola Dougl.), ponderosa pine (Pinus ponderosa
      Laws.), and Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco var. glauca)
      growing in northern Idaho. Material was obtained by the stem analysis method from
      rings laid down in the upper portion of the crown throughout each tree's life.
      The sampling protocol minimized variation caused by changing light regimes within
      each tree. Autoregressive moving average (ARMA) models were used to describe the
      autocorrelation structure over time. Three time series were analyzed for each
      tree: the stable carbon isotope ratio (delta(13)C); discrimination (delta); and
      the difference between ambient and internal CO(2) concentrations (c(a) - c(i)).
      The effect of converting from ring cellulose to whole-leaf tissue did not affect
      the analysis because it was almost completely removed by the detrending that
      precedes time-series analysis. A simple linear or quadratic model adequately
      described the time trend. The residuals from the trend had a constant mean and
      variance, thus ensuring stationarity, a requirement for autocorrelation analysis.
      The trend over time for c(a) - c(i) was particularly strong (R(2) = 0.29-0.84).
      Autoregressive moving average analyses of the residuals from these trends
      indicated that two-thirds of the individual tree series contained significant
      autocorrelation, whereas the remaining third were random (white noise) over time.
      We were unable to distinguish between individuals with and without significant
      autocorrelation beforehand. Significant ARMA models were all of low order, with
      either first- or second-order (i.e., lagged 1 or 2 years, respectively) models
      performing well. A simple autoregressive (AR(1)), model was the most common. The
      most useful generalization was that the same ARMA model holds for each of the
      three series (delta(13)C, delta, c(a) - c(i)) for an individual tree, if the time
      trend has been properly removed for each series. The mean series for the two pine
      species were described by first-order ARMA models (1-year lags), whereas the
      Douglas-fir mean series were described by second-order models (2-year lags) with
      negligible first-order effects. Apparently, the process of constructing a mean
      time series for a species preserves an underlying signal related to delta(13)C
      while canceling some of the random individual tree variation. Furthermore, the
      best model for the overall mean series (e.g., for a species) cannot be inferred
      from a consensus of the individual tree model forms, nor can its parameters be
      estimated reliably from the mean of the individual tree parameters. Because two
      thirds of the individual tree time series contained significant autocorrelation,
      the normal assumption of a random structure over time is unwarranted, even after
      accounting for the time trend. The residuals of an appropriate ARMA model satisfy
      the independence assumption, and can be used to make hypothesis tests.

PMID- 11581017
TI  - Photosynthetic light response of flooded cherrybark oak (Quercus pagoda)
      seedlings grown in two light regimes.
AB  - Two-year-old cherrybark oak (Quercus pagoda Raf.) seedlings raised in full or
      partial (27%) sunlight were flooded for 30 days to study the effects of light
      availability and root inundation on photosynthetic light response. Compared with
      seedlings receiving full sunlight, seedlings receiving partial sunlight developed
      leaves with 90% greater blade area, 26% less mass per unit volume, and 35% lower
      nitrogen (N) concentration per unit area, leading to a 15% reduction in leaf
      photosynthetic capacity when carbon exchange rates were based on blade area.
      However, when carbon exchange rates were based on leaf mass, leaves acclimated to
      partial sunlight exhibited a 15% greater photosynthetic capacity realized
      primarily through an increased initial slope of the photosynthetic light response
      (A/PPFD) curve and increased net photosynthesis at leaf saturation (Amax). Short
      term flooding increased leaf mass per unit area more than 19%, reduced foliar N
      concentrations per unit dry mass by 19%, and initiated reductions in Amax and
      apparent quantum yield (phi) of seedlings in both light regimes. Greatest
      impairment of Amax (56% area basis, 65% mass basis) and phi (40%) were observed
      in leaves receiving full sunlight, and the declines were concomitant with a 35%
      decrease in chlorophyll concentration. Flooding also depressed instantaneous
      photosynthetic N-use efficiency (PPNUE) such that Amax decreased 54%, and the
      initial slope of PPNUE/PPFD curves decreased 33 and 50% for leaves acclimated to
      partial and full sunlight, respectively. The A/PPFD patterns indicated that the
      magnitude of flood-induced inhibition of the photosynthetic mechanism of
      cherrybark oak seedlings is determined partly by the light environment.

PMID- 11581018
TI  - Foliar nitrogen concentrations and natural abundance of (15)N suggest nitrogen
      allocation patterns of Douglas-fir and mycorrhizal fungi during development in
      elevated carbon dioxide concentration and temperature.
AB  - Pseudotsuga menziesii (Mirb.) Franco (Douglas-fir) seedlings were grown in a 2 x
      2 factorial design in enclosed mesocosms at ambient temperature or 3.5 degrees C
      above ambient, and at ambient CO2 concentration ([CO2]) or 179 ppm above ambient.
      Two additional mesocosms were maintained as open controls. We measured the extent
      of mycorrhizal infection, foliar nitrogen (N) concentrations on both a weight
      basis (%N) and area basis (Narea), and foliar delta15N signatures (15N/14N
      ratios) from summer 1993 through summer 1997. Mycorrhizal fungi had colonized
      nearly all root tips across all treatments by spring 1994. Elevated [CO2] lowered
      foliar %N but did not affect N(area), whereas elevated temperature increased both
      foliar %N and Narea. Foliar delta15N was initially -1 per thousand and dropped by
      the final harvest to between -4 and -5 per thousand in the enclosed mesocosms,
      probably because of transfer of isotopically depleted N from mycorrhizal fungi.
      Based on the similarity in foliar delta15N among treatments, we conclude that
      mycorrhizal fungi had similar N allocation patterns across CO2 and temperature
      treatments. We combined isotopic and Narea data for 1993-94 to calculate fluxes
      of N for second- and third-year needles. Yearly N influxes were higher in second
      year needles than in third-year needles (about 160 and 50% of initial leaf N,
      respectively), indicating greater sink strength in the younger needles. Influxes
      of N in second-year needles increased in response to elevated temperature,
      suggesting increased N supply from soil relative to plant N demands. In the
      elevated temperature treatments, N effluxes from third-year needles were higher
      in seedlings in elevated [CO2] than in ambient [CO2], probably because of
      increased N allocation below ground. We conclude that N allocation patterns
      shifted in response to the elevated temperature and [CO2] treatments in the
      seedlings but not in their fungal symbionts.

PMID- 11581019
TI  - Seasonal variation in xylem pressure of walnut trees: root and stem pressures.
AB  - Measurements of air and soil temperatures and xylem pressure were made on 17-year
      old orchard trees and on 5-year-old potted trees of walnut (Juglans regia L.).
      Cooling chambers were used to determine the relationships between temperature and
      sugar concentration ([glucose] + [fructose] + [sucrose], GFS) and seasonal
      changes in xylem pressure development. Pressure transducers were attached to
      twigs of intact plants, root stumps and excised shoots while the potted trees
      were subjected to various temperature regimes in autumn, winter and spring.
      Osmolarity and GFS of the xylem sap (apoplast) were measured before and after
      cooling or warming treatments. In autumn and spring, xylem pressures of up to 160
      kPa were closely correlated with soil temperature but were not correlated with
      GFS in xylem sap. High root pressures were associated with uptake of mineral
      nutrients from soil, especially nitrate. In autumn and spring, xylem pressures
      were detected in root stumps as well as in intact plants, but not in excised
      stems. In contrast, in winter, 83% of the xylem sap osmolarity in both excised
      stems and intact plants could be accounted for by GFS, and both GFS and
      osmolarity were inversely proportional to temperature. Plants kept at 1.5 degrees
      C developed positive xylem pressures up to 35 kPa, xylem sap osmolarities up to
      260 mosmol l(-1) and GFS concentrations up to 70 g l(-1). Autumn and spring xylem
      pressures, which appeared to be of root origin, were about 55% of the theoretical
      pressures predicted by osmolarity of the xylem sap. In contrast, winter pressures
      appeared to be of stem origin and were only 7% of the theoretical pressures,
      perhaps because of a lower stem water content during winter.

PMID- 11581020
TI  - Changes in fine root production and longevity in relation to water and nutrient
      availability in a Norway spruce stand in northern Sweden.
AB  - The PEACH computer simulation model of reproductive and vegetative growth of
      peach trees (Grossman and DeJong 1994) was adapted to estimate seasonal nitrogen
      (N) dynamics in organs of mature peach (Prunus persica (L.) Batsch cv. O'Henry)
      trees grown with high and low soil N availability. Seasonal N accumulation
      patterns of fruits, leaves, stems, branches, trunk and roots of mature, cropping
      peach trees were modeled by combining model predictions of organ dry mass
      accumulation from the PEACH model with measured seasonal organ N concentrations
      of trees that had been fertilized with either zero or 200 kg N ha(-1) in April.
      The results provided a comparison of the N use of perennial and annual organs
      during the growing season for trees growing under both low and high N
      availability. Nitrogen fertilization increased tree N content by increasing organ
      dry masses and N concentrations during the fruit growing season. Dry mass of
      current-year vegetative growth was most affected by N fertilization. Whole-tree N
      content of fertilized trees was almost twice that of non-fertilized trees.
      Although N use was higher in fertilized trees, calculated seasonal N accumulation
      patterns were similar for trees in both treatments. Annual organs exhibited
      greater responses to N fertilization than perennial organs. Estimated mean daily
      N use per tree remained nearly constant from 40 days after anthesis to harvest.
      The calculations indicated that fertilized trees accumulated about 1 g N tree(-1)
      day(-1), twice that accumulated by non-fertilized trees. Daily N use by the
      fertilized orchard was calculated to be approximately 1 kg N ha(-1), whereas it
      was approximately 0.5 kg N ha(-1) for the non-fertilized trees. During the first
      25-30 days of the growing season, all N use by growing tissues was apparently
      supplied by storage organs. Nitrogen release from storage organs for current
      growth continued until about 75 days after anthesis in both N treatments.

PMID- 11581021
TI  - Evidence for increased sensitivity to nutrient and water stress in a fast-growing
      hybrid willow compared with a natural willow clone.
AB  - The hypothesis that fast-growing breeds of willow (Salix spp.) are more sensitive
      to nutrient and water stress and less efficient in nutrient- and water-use than
      slower-growing natural willow clones was tested. Cuttings of a natural clone of
      S. viminalis L. collected in Sweden (L78183) and a hybrid clone of S. schwerinii
      E. Wolf. x S. viminalis L. ("Tora") were grown outdoors in pots under various
      experimental conditions in a full-factorial design. The experimental conditions
      included three fertilization, two irrigation and two temperature regimes.
      Classical growth analysis techniques, based on an initial and a final harvest,
      were used as a screening method, together with calculation of intrinsic water-use
      efficiency (foliar carbon isotope ratio; delta13C). In addition, nitrogen-use
      efficiency was calculated as the product of nitrogen productivity and mean
      residence time of nitrogen on an annual basis. There were significant differences
      in plant structural parameters (leaf area ratio, specific leaf area) and water
      use efficiency between the clones. Furthermore, several clone x treatment
      interaction effects on various growth parameters indicated that the clones
      adapted to specific environments in different ways. "Tora" plants produced up to
      25% more shoot biomass than plants of the natural clone in response to high rates
      of fertilization and irrigation, whereas clone ranking was reversed in most other
      treatments. The results support the hypothesis that fast-growing hybrids are more
      sensitive to nutrient and water stress than slower-growing natural clones. The
      hypothesis that natural clones have higher resource-use efficiency than fast
      growing hybrids was supported with respect to water, but not nitrogen.

PMID- 11581022
TI  - Physiological variation among Populus fremontii populations: short- and long-term
      relationships between delta13C and water availability.
AB  - Different populations of widely distributed species can experience dramatically
      different climatic conditions that may influence physiological activity,
      specifically carbon assimilation and water use. Populus fremontii Wats. (Fremont
      cottonwood) populations are found near rivers of varying size along a
      precipitation gradient from New Mexico to northern California. Climatic
      differences among populations may lead to physiological differences because P.
      fremontii is sensitive to water availability. To assess physiological variation
      among populations, we collected foliage and wood samples from 13 populations that
      experience different precipitation and stream flow regimes and analyzed the
      samples for carbon isotope composition (delta13C). Wood delta13C served as a
      lifetime-averaged indicator of water-use efficiency (WUE), whereas foliage
      delta13C provided as an estimate of WUE during the growing season of collection.
      We found approximately 3.4 per thousand variation in delta13C among populations
      for both foliage (-31.1 to -27.9 per thousand) and wood (-28.3 to -24.7 per
      thousand). Wood delta13C was, on average, 2.8 per thousand more enriched than
      foliage. Some of the variation in wood delta13C can be explained by variation in
      elevation of the study sites. We constructed total precipitation and mean stream
      flow variables based on the length of the growing season at each study site and
      analyzed for a relationship between delta13C, precipitation and stream flow. A
      significant relationship between foliage delta13C and precipitation was found,
      but water availability did not explain a significant fraction of the variation in
      wood delta13C. The data suggest that water availability can account for some of
      the delta13C variation among populations but, given the large residual variances,
      other factors are important.

PMID- 11581024
TI  - Screening for amblyopia in preverbal children: improved grading criteria for
      hyperopia.

PMID- 11581025
TI  - Pepper spray in the eye.

PMID- 11581026
TI  - Gaze-evoked amaurosis.

PMID- 11581028
TI  - Mapping the visual field.

PMID- 11581029
TI  - Hypopyon after amniotic membrane transplantation.

PMID- 11581031
TI  - Ocular hypertensive response to dexamethasone.

PMID- 11581035
TI  - Visual acuity results after plaque radiotherapy.

PMID- 11581036
TI  - Risk factors in AION.

PMID- 11581037
TI  - Sclerectomy versus trabeculectomy in POAG.

PMID- 11581039
TI  - Racial disparities in vision impairment and blindness: causes and future research
      direction.

PMID- 11581040
TI  - Adverse intraoperative medical events and their association with anesthesia
      management strategies in cataract surgery.
AB  - OBJECTIVE: To compare adverse medical events by different anesthesia strategies
      for cataract surgery. DESIGN: Prospective cohort study. PARTICIPANTS: Patients 50
      years of age and older undergoing 19,250 cataract surgeries at nine centers in
      the United States and Canada between June 1995 and June 1997. INTERVENTION: Local
      anesthesia applied topically or by injection, with or without oral and
      intravenous sedatives, opioid analgesia, hypnotics, and diphenhydramine
      (Benadryl). MAIN OUTCOME MEASURES: Intraoperative and postoperative adverse
      medical events. RESULTS: Twenty-six percent of surgeries were performed with
      topical anesthesia and the remainder with injection anesthesia. There was no
      increase in deaths and hospitalizations associated with any specific anesthesia
      strategy. No statistically significant difference was observed in the prevalence
      of intraoperative events between topical and injection anesthesia without
      intravenous sedatives (0.13% and 0.78%, respectively). The use of intravenous
      sedatives was associated with a significant increase in adverse events for
      topical (1.20%) and injection anesthesia (1.18%), relative to topical anesthesia
      without intravenous sedation. The use of short-acting hypnotic agents with
      injection anesthesia was also associated with a significant increase in adverse
      events when used alone (1.40%) or in combination with opiates (1.75%), sedatives
      (2.65%), and with the combination of opiates and sedatives (4.04%). These
      differences remained after adjusting for age, gender, duration of surgery, and
      American Society of Anesthesiologists risk class. CONCLUSIONS: Adjuvant
      intravenous anesthetic agents used to decrease pain and alleviate anxiety are
      associated with increases in medical events. However, cataract surgery is a safe
      procedure with a low absolute risk of medical complications with either topical
      or injection anesthesia. Clinicians should weigh the risks and benefits of their
      use for individual patients.

PMID- 11581041
TI  - Spontaneous late dislocation of intraocular lens within the capsular bag in
      pseudoexfoliation patients.
AB  - PURPOSE: To identify a delayed complication of cataract surgery in patients with
      zonular weakness caused by pseudoexfoliation syndrome. DESIGN: Retrospective
      observational case series. PARTICIPANTS: Eight eyes in seven patients with
      clinically diagnosed pseudoexfoliation syndrome who had undergone previous
      uncomplicated cataract extraction and placement of a posterior chamber
      intraocular lens. METHODS: This study evaluated eight cases of late spontaneous
      dislocation of posterior chamber intraocular lenses within the capsular bag in
      patients with pseudoexfoliation syndrome. Data were gathered retrospectively from
      patients' operative reports, medical records, and pathology reports. MAIN OUTCOME
      MEASURES: (1) Interval between original surgery and dislocation; (2) final best
      corrected visual acuity and ocular outcome. RESULTS: All patients had a diagnosis
      of pseudoexfoliation syndrome and had previously undergone uncomplicated cataract
      surgery. No patient had any other predisposing factors that would lead to zonular
      dehiscence or weakness. Delayed dislocation of the entire capsular bag containing
      the intraocular lens (IOL) occurred spontaneously in all cases. Mean time from
      IOL implantation to dislocation was approximately 85 months (7 years and 1 month;
      range, 57-115 months) after surgery. Seven eyes were treated successfully with
      IOL exchange: six with placement of an anterior chamber IOL and one with scleral
      fixation of a posterior chamber IOL. The remaining case was treated by scleral
      fixation of the dislocated IOL. Gross pathology analysis of seven cases confirmed
      the presence of the IOL within the intact capsular bag. Six eyes have achieved
      final best-corrected visual acuity of 20/40 or better. CONCLUSION: Patients with
      pseudoexfoliation syndrome may be at risk for delayed spontaneous dislocation of
      IOL within the capsular bag after uncomplicated cataract surgery. Awareness of
      this newly recognized long-term complication may justify a reevaluation of
      surgical considerations for cataract removal in these patients.

PMID- 11581042
TI  - Evaluation of photorefractive keratectomy retreatments after regressed myopic
      laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the results of photorefractive keratectomy (PRK)
      enhancements in eyes previously treated by myopic laser in situ keratomileusis
      (LASIK) showing an undercorrection due to either a refractive regression or a
      primary undercorrection, when an in-the-bed enhancement was not advisable because
      of residual stromal thickness limitations. DESIGN: Noncomparative, prospective,
      interventional case series. PARTICIPANTS: Seventeen eyes of 17 patients
      previously treated by LASIK for a spherical equivalent (SE) correction of -8.125
      to -12.50 diopters (D; mean, -9.45 +/- 1.01 D), that after a follow-up of 6 to 14
      months ended up with a refraction of -1.50 to -3.75 D (SE; mean, -2.48 +/- 0.74
      D). Intended flap thickness was 160 microm for all eyes. In all cases, the
      residual stromal bed under the flap was considered too thin (255-305 microm) to
      allow an in-the-bed enhancement without exceeding an assumed safety thickness
      limit (250 microm). INTERVENTION: Eyes were treated by PRK at least 6 months
      after LASIK. The PRK ablation parameters (diameter, attempted correction) were
      selected to avoid theoretical flap perforation. The deepest ablation was 60
      microm, for a -3.75-D correction. We used a Bausch & Lomb 217 C excimer laser
      (Bausch & Lomb, Rochester, New York). MAIN OUTCOME MEASURES: Refraction,
      uncorrected and best-corrected visual acuity (BCVA), slit-lamp evidence of
      corneal opacity or other visible complications, and corneal topography. RESULTS:
      Although the initial postoperative period was characterized by very satisfactory
      refractive results (mean SE error at 1 month, -0.04 +/- 0.37 D; range, +0.75 to 
      0.625 D), during follow-up, a dense haze (grade 3 and 4) developed in 14 eyes
      (82.3%) that induced a further myopic regression (SE, -1.725 to -5.50 D; mean, 
      3.11 D) and BCVA loss (two to six lines). These 14 eyes underwent a further
      surgical treatment to remove the severe haze at 3 to 10 months after PRK.
      CONCLUSIONS: Based on these results, we strongly advise against PRK as a possible
      option to correct eyes previously treated by myopic LASIK that resulted in an
      undercorrection.

PMID- 11581043
TI  - Laser in situ keratomileusis results after intrastromal corneal ring segments
      (Intacs).
AB  - OBJECTIVE: To evaluate the safety and efficacy of laser in situ keratomileusis
      (LASIK) after removal of intrastromal corneal ring segments (Intacs, KeraVision,
      Fremont, CA) from the cornea. DESIGN: Single-center, noncomparative,
      interventional, consecutive case series. PARTICIPANTS: Nine eyes of nine
      consecutive patients who had undergone LASIK after Intacs of experimental design
      removal were analyzed for this study. INTERVENTION: A standard LASIK procedure
      was performed with the Nidek EC 5000 excimer laser (Nidek, Gamagori, Japan) at
      intervals between 4 and 10 months after Intacs explantation. A Nidek MK 2000
      microkeratome (Nidek, Gamagori, Japan) or a Chiron Automated Corneal Shaper
      (Bausch & Lomb, Claremont, CA) with a 130- to 180-microm thickness plate was used
      to create a nasal hinged flap in a plane superficial to the previous Intacs
      channel. MAIN OUTCOME MEASURES: Uncorrected visual acuity, manifest refraction,
      best spectacle-corrected visual acuity, and topography were measured
      preoperatively and at months 1, 3, 6, and 12 after LASIK. RESULTS: Faint residual
      scarring in the channels after Intacs removal was seen in all patients. No
      difficulties were encountered during the ablation or flap replacement. Eight of
      nine patients had 20/20 or better uncorrected visual acuity after a single LASIK
      procedure. Mean spherical equivalent at 12 months was -0.6, ranging from -1.25 to
      +0.25 diopter. One patient had glare develop secondary to superior corneal
      thinning and scarring after implantation of a nonstandard Intacs. No patient lost
      lines of best spectacle-corrected vision after LASIK. CONCLUSION: Reversibility
      of the myopic Intacs is demonstrated. Removal of Intacs may be followed by a safe
      and effective LASIK for low to moderate myopia.

PMID- 11581044
TI  - Evaluation of corneal stromal changes in vivo after laser in situ keratomileusis
      with confocal microscopy.
AB  - PURPOSE: To assess by in vivo confocal microscopy the modifications of the
      corneal stroma after laser in situ keratomileusis (LASIK) for myopia. DESIGN:
      Nonrandomized comparative (self-controlled) trial. PARTICIPANTS: Sixteen eyes of
      13 patients were examined before surgery and at days 8, 30, and 90, and 9 eyes
      were examined at 6 months postoperatively using an in vivo confocal microscope.
      TESTING/INTERVENTION: Stromal morphologic changes, keratocyte density, flap
      thickness, and subclinical haze were evaluated and compared at different time
      points. LASIK was performed with a Flapmaker microkeratome (Solan Ophthalmic
      products, Jacksonville, FL) and a Lasersight LSX excimer laser (LaserSight
      Technologies Inc., Winter Park, FL). MAIN OUTCOME MEASURE: Confocal microscopy
      results. RESULTS: Microfolds at the Bowman's layer were found in most eyes, as
      well as variable reflectivity particles (pa) located at the interface level in
      all eyes examined postoperatively. The density of these particles significantly
      decreased with time with, respectively, 504 +/- 101 pa/mm2 at day 8 and 380 +/-
      111 pa/mm2 at day 30 (P = 0.003), 332 +/- 100 pa/mm2 at month 3 and 312 +/- 40
      pa/mm2 at month 6. The mean flap and the activated-cells area thicknesses were,
      respectively, 102 +/- 26 microm and 61 +/- 19 microm and showed significant
      negative correlation (P < 0.0001). The intensity of the added peak (47.3 microm
      8.6%), corresponding to the subclinical haze, realized by Z-scan measure, was
      also negatively correlated with flap thickness (P = 0.01). Keratocyte (k) density
      quantified in the posterior stroma significantly increased from day 0 (480 +/- 67
      k/mm2) to day 8 (701 +/- 41 k/mm2, P < 0.0001 compared with day 0) and day 30
      (917 +/- 143 k/mm2, P = 0.0006, compared with day 0) but significantly decreased
      at 3 months postoperatively (597 +/- 56 k/mm2, P < 0.0001 compared with day 30)
      to reach the initial level at month 6 (502 +/- 41 k/mm2, nonsignificant compared
      with day 0). There was no correlation between preoperative or postoperative
      spherical equivalent and the density of particles, keratocytes, and the haze
      intensity. CONCLUSIONS: This study confirms the presence of microfolds and
      particles at the interface level, as well as subclinical impairment. Evaluation
      of keratocyte density constitutes a major contribution of confocal microscopy
      toward an understanding of the keratocyte response to corneal wound healing after
      corneal refractive surgery. Moreover, flap thickness seems to be involved in the
      postoperative cellular activation with a higher response when thin.

PMID- 11581045
TI  - Prevalence and causes of visual impairment in The Barbados Eye Study.
AB  - OBJECTIVE: To determine the prevalence and causes of low vision and blindness in
      a predominantly black population. DESIGN: Population-based prevalence study of a
      simple random sample of Barbados-born citizens aged 40 to 84 years. PARTICIPANTS:
      Four thousand seven hundred nine persons (84% participation). METHODS: The
      standardized protocol included best-corrected visual acuity (with a Ferris-Bailey
      chart), automated perimetry, lens gradings (LOCS II), and an interview.
      Participants with visual acuity of worse than 20/30, other positive findings, and
      a 10% sample also had an ophthalmologic examination that evaluated the cause and
      extent of vision loss (resulting from that cause), if any. MAIN OUTCOME MEASURES:
      Low vision and blindness were defined as visual acuity in the better eye between
      6/18 and 6/120 and visual acuity worse than 6/120, respectively (World Health
      Organization [WHO] criteria). RESULTS: Of the 4631 participants with complete
      examinations, 4314 (93%) reported their race as black, 184 (4%) reported their
      race as mixed (black and white), and 133 (3%) reported their race as white or
      other. Low vision was found in 5.9% of the black, 2.7% of the mixed, and 3.0% of
      white or other participants. Bilateral blindness was similar for black and mixed
      race participants (1.7% and 1.6%, respectively) and was not found in whites.
      Among black and mixed participants, the prevalence of low vision increased with
      age (from 0.3% at 40-49 years to 26.8% at 80 years or older). The prevalence of
      blindness was higher (P < 0.001) for men than women at each age group (0.5%
      versus 0.3% at ages 40-49 and 10.9% versus 7.3% at 80 years or more). Sixty
      percent of blindness was due to open-angle glaucoma and age-related cataract,
      each accounting for more than one fourth of cases. Other major causes were optic
      atrophy or neuropathy and macular and other retinal diseases. Few cases of
      blindness were due to diabetic retinopathy (1.4%), and none were due to age
      related macular degeneration. CONCLUSIONS: Using the WHO criteria, prevalence of
      visual impairment was high in this African-origin population, particularly at
      older ages. Most blindness was due to open-angle glaucoma and cataract, with open
      angle glaucoma causing a higher proportion of blindness than previously reported.
      The increased prevalence of blindness in men may be due to the increased male
      prevalence of glaucoma in this population and warrants further investigation.
      Results underline the need for blindness prevention programs, with emphasis on
      effective treatment of age-related cataract and enhancing strategies for early
      detection and treatment of open-angle glaucoma.

PMID- 11581046
TI  - Changes in visual acuity in a population over a 10-year period : The Beaver Dam
      Eye Study.
AB  - PURPOSE: To describe the change in visual acuity in a 10-year period. DESIGN:
      Population-based cohort study. PARTICIPANTS: Included 3684 persons 43 to 86 years
      of age at the time of a baseline examination in 1988 to 1990, living in Beaver
      Dam, Wisconsin, at a follow-up examination in 1993 to 1995 and/or 1998 to 2000.
      METHODS: Best-corrected visual acuity was measured, after refraction, with
      logarithm of the minimum angle of resolution charts using a modification of the
      Early Treatment Diabetic Retinopathy Study protocol. MAIN OUTCOMES MEASURES:
      Doubling of the visual angle and incidence of visual impairment. RESULTS: The
      change in the mean number of letters read correctly over the 10-year period
      varied in the right eye from -0.9 (standard deviation [SD] = 5.5) and in the left
      eye from -1.2 (SD = 6.6) in people between 43 and 54 years of age to -11.0 (SD =
      20.0) in the right eye and -12.6 (SD = 20.4) in the left eye in people 75 years
      of age or older (n = 184) at baseline. Over the 10-year period, 5.9% of the
      population had impaired vision (20/40 or worse in the better eye) develop, 0.8%
      had severe visual impairment (20/200 or worse in the better eye) develop, 4.8%
      had doubling of the visual angle, and 3.9% had improved vision. People who were
      75 years of age or older at baseline were 15.0 times (95% confidence interval
      [CI], 10.9-20.6; P < 0.001) as likely to have impaired vision develop, 9.3 times
      (95% CI, 6.5-13.3; P < 0.001) as likely to have doubling of the visual angle, and
      19.8 times as likely (95% CI, 8.4-46.4; P < or = 0.001) to have severe visual
      impairment develop than people younger than 75 years of age at baseline. For the
      82 persons 75 years of age or older, currently residing in a nursing or group
      home at follow-up, they were 2.6 times (95% CI, 1.45-4.52) as likely to have
      impaired vision develop, 1.6 times (95% CI, 0.47-5.62) as likely to have severely
      impaired vision develop, and 3.6 times (95% CI, 1.96-6.78) as likely to have had
      a doubling of the visual angle than those not residing in a nursing or group home
      at follow-up. CONCLUSIONS: These data provide precise population-based estimates
      of the 10-year incidence of loss of vision over a wide spectrum of ages and show
      that decreased visual acuity in people 75 years of age after 10 years is a common
      finding, especially in those who are admitted to nursing or group homes.

PMID- 11581047
TI  - Evidence-based recommendations for the diagnosis and treatment of neovascular
      glaucoma.
AB  - PURPOSE: To succinctly update information on the pathogenesis, etiology,
      diagnosis, and treatment of neovascular glaucoma based on a systematic review of
      available literature and to provide summary recommendations rated for their
      importance to clinical outcome. CLINICAL RELEVANCE: Neovascular glaucoma is a
      devastating ocular disease that often results in loss of vision. The current
      standard of care includes retinal ablation and control of increased intraocular
      pressure with medical and surgical therapy. LITERATURE REVIEW METHODOLOGY: The
      authors conducted a MEDLINE literature search of articles published in English
      from 1966 to the present. Each article reviewed was rated as to the strength of
      evidence it provided, and summary ratings for the strength of evidence supporting
      clinical recommendations were generated. RESULTS: Level A (most important to
      patient outcome) recommendations for the diagnosis of neovascular glaucoma
      include a high index of suspicion, a full ocular examination including undilated
      gonioscopy, and pupil examination. In regard to treatment, Level A
      recommendations include treatment of the underlying disease origin, complete
      panretinal photocoagulation (if retinal ischemia is a factor), and medical
      control of both elevated intraocular pressure and inflammation. Level B
      recommendations (moderately important to patient outcome) encompass glaucoma
      surgery to control intraocular pressure when medical therapy is unsuccessful,
      although the ideal surgical procedure is unknown. Currently, trabeculectomy with
      antimetabolite therapy, aqueous shunt implants, and diode laser
      cyclophotocoagulation are the preferred surgical treatment options. CONCLUSIONS:
      The current literature on neovascular glaucoma has few articles that provide
      strong evidence in support of therapy recommendations (level I). Future research
      studies are needed to address areas in which the current evidence is moderately
      strong (level II) or weak, consisting only of a consensus of expert opinion
      (level III). Whenever practicable, these studies should be prospective,
      randomized clinical trials.

PMID- 11581050
TI  - Long-term surgical outcomes of patients with glaucoma secondary to the
      iridocorneal endothelial syndrome.
AB  - PURPOSE: To report the long-term outcomes of patients with iridocorneal
      endothelial (ICE) syndrome who required surgery for glaucoma. DESIGN:
      Retrospective, noncomparative case series. PARTICIPANTS: Twenty-six patients with
      ICE syndrome who underwent surgery for glaucoma at one institution between
      January 1987 and January 2000. MAIN OUTCOME MEASURES: Intraocular pressure (IOP),
      visual acuity, number of glaucoma medications, and further surgical interventions
      were measured. RESULTS: Five eyes had a trabeculectomy with an antifibrotic agent
      alone, seven eyes had a trabeculectomy with an antifibrotic agent and a
      subsequent glaucoma drainage implant (GDI), and 14 eyes had a GDI alone. In eyes
      that underwent a trabeculectomy with an antifibrotic agent, preoperative IOP was
      reduced from a mean of 38.8 +/- 10.5 mmHg on 2.3 +/- 0.8 glaucoma medications to
      a mean of 11.8 +/- 4.3 mmHg on 1.2 +/- 1.4 medications at last follow-up after
      surgery (83.8 +/- 40.3 months). In eyes that underwent GDI surgery, preoperative
      IOP was reduced from a mean of 35.2 +/- 13.0 mmHg on 2.0 +/- 1.3 glaucoma
      medications to a mean of 8.7 +/- 11.2 mmHg on 1.2 +/- 1.1 medications at last
      follow-up after surgery (50.5 +/- 40.7 months). Twenty-four eyes (92%) had an IOP
      less than 22 mmHg, and 22 eyes (85%) had visual acuity 20/400 or better at last
      follow-up (55.8 +/- 41.5 months). Mean number of glaucoma surgeries per patient
      over the follow-up period was 1.6 +/- 1.2. Trabeculectomy with antifibrotic
      agents had a survival of 73% at 1 year, 44% at 3 years, and 29% at 5 years.
      Glaucoma drainage implants had a survival of 71% at 1 year, 71% at 3 years, and
      53% at 5 years. CONCLUSIONS: Glaucoma associated with ICE syndrome can be managed
      successfully surgically, although multiple procedures are often needed.

PMID- 11581049
TI  - Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS).
AB  - OBJECTIVE: Central corneal thickness influences intraocular pressure (IOP)
      measurement. We examined the central corneal thickness of subjects in the Ocular
      Hypertension Treatment Study (OHTS) and determined if central corneal thickness
      is related to race. DESIGN: Cross-sectional study. PARTICIPANTS: One thousand
      three hundred one OHTS subjects with central corneal thickness measurements.
      INTERVENTION: Central corneal thickness was determined with ultrasonic
      pachymeters of the same make and model at all clinical sites of the OHTS. MAIN
      OUTCOME MEASURES: Correlation of mean central corneal thickness with race,
      baseline IOP, refraction, age, gender, systemic hypertension, and diabetes.
      RESULTS: Mean central corneal thickness was 573.0 +/- 39.0 microm. Twenty-four
      percent of the OHTS subjects had central corneal thickness > 600 microm. Mean
      central corneal thickness for African American subjects (555.7 +/- 40.0 microm; n
      = 318) was 23 microm thinner than for white subjects (579.0 +/- 37.0 microm; P <
      0.0001). Other factors associated with greater mean central corneal thickness
      were younger age, female gender, and diabetes. CONCLUSIONS: OHTS subjects have
      thicker corneas than the general population. African American subjects have
      thinner corneas than white subjects in the study. The effect of central corneal
      thickness may influence the accuracy of applanation tonometry in the diagnosis,
      screening, and management of patients with glaucoma and ocular hypertension.

PMID- 11581051
TI  - Long-term follow-up of traumatic glaucoma treated with Molteno implants.
AB  - PURPOSE: To determine the long-term outcomes of patients with traumatic glaucoma
      treated with Molteno implants at Dunedin Hospital, New Zealand. DESIGN:
      Prospective, noncomparative, interventional case series. PARTICIPANTS: Thirty
      eight patients with traumatic glaucoma and with a mean follow-up of 10.9 years.
      INTERVENTION: Insertion of Molteno implant. MAIN OUTCOME MEASURES: Intraocular
      pressure (IOP) and intraocular pressure-related surgical interventions after
      Molteno implant insertion. RESULTS: Insertion of a Molteno implant controlled the
      IOP at 21 mmHg or less (with or without hypotensive medication) with a
      probability of 0.80 (95% confidence interval [CI], 0.66, 0.93) at 5 years and
      0.72 (95% CI, 0.56, 0.88) at 10 years. At final follow-up, intraocular pressure
      was controlled solely with the implant in 26 cases and controlled with the
      addition of hypotensive medication in three cases, whereas nine eyes were
      failures. Eleven patients (29%) underwent intervention for implant repositioning
      or tube orifice blockage. Thirty-four double- and six single-plate Molteno
      implants were inserted. Two patients had implants replaced. Seventy-nine percent
      became aphakic or pseudophakic from their trauma before or at the time of Molteno
      implant insertion. There were no exclusions resulting from extensive ocular
      damage. CONCLUSIONS: Insertion of Molteno implants in traumatic glaucoma produced
      intraocular pressure control at long-term follow-up in 76% of cases.

PMID- 11581052
TI  - Transscleral contact krypton laser cyclophotocoagulation for treatment of
      glaucoma in children and young adults.
AB  - PURPOSE: To evaluate the usefulness of the krypton laser for transscleral contact
      cyclophotocoagulation (CPC) in the treatment of glaucoma in young patients.
      DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS:
      Transscleral contact krypton laser CPC was performed in 27 glaucomatous eyes of
      22 young patients (mean age, 10.5 +/- 5.6 years; range, 11 months-19.4 years).
      METHODS: The treatment was delivered by means of a fiberoptic probe with
      compression of the sclera by the probe. The power used was 300 to 500 W per
      application at the tip of the probe with an exposure time of 10 seconds. MAIN
      OUTCOME MEASURES: The primary outcome measure is a change in intraocular pressure
      (IOP). RESULTS: Of the patients who received CPC in both eyes, one eye was
      randomly chosen for statistical analysis. The mean overall follow-up time was
      43.3 +/- 25.3 (median, 36.5; range, 1-82) months after the initial CPC.
      Preoperatively, the mean intraocular pressure was 35.0 +/- 7.9 mmHg (n = 22).
      After one or more CPCs, the mean IOP was decreased to 21.5 +/- 8.7 mmHg (n = 22)
      at 1 month (P < 0.001), to 23.4 +/- 8.6 mmHg (n = 18) at 3 months (P < 0.001), to
      25.0 +/- 12.1 mmHg (n = 19) at 6 months (P < 0.01), to 22.1 +/- 9.1 mmHg (n = 16)
      at 1 year (P < 0.01), and to 22.6 +/- 10.3 (n = 11) at 2 years (P < 0.01). After
      one or more krypton CPCs, but no other glaucoma procedures, an IOP level of 8 to
      21 mmHg or a decrease in IOP of more than 30% was obtained in 14 of 22 (64%) eyes
      at the last follow-up. No permanent hypotonia, phthisis bulbi, or devastating CPC
      related complications were noted. CONCLUSIONS: Krypton laser CPC is a well
      tolerated means of lowering IOP in young patients with glaucoma, but repeated
      treatments may be needed.

PMID- 11581053
TI  - Delayed suprachoroidal hemorrhage after glaucoma filtration procedures.
AB  - OBJECTIVES: To determine the incidence of, risk factors for, and outcomes of
      delayed suprachoroidal hemorrhage (DSCH) after glaucoma filtration surgery.
      DESIGN: Retrospective case-control study. PARTICIPANTS: All patients undergoing
      glaucoma filtration procedures between 1986 and 2000 at Indiana University who
      were diagnosed postoperatively with suprachoroidal hemorrhage. A total of 66
      patients with DSCH were identified. These were compared with a randomly selected
      group of patients who underwent similar procedures but did not have
      suprachoroidal hemorrhage. METHODS: Total cases of DSCH were initially compared
      with the total number of glaucoma surgeries to determine the overall incidence
      and the incidence in the different procedures. Subsequently, a case-control study
      was performed comparing the group with hemorrhage to the control group to
      identify risk factors. Finally, outcomes and prognostic factors were determined
      by comparing vision preoperatively and postoperatively and parameters of patients
      with good and poor outcomes. MAIN OUTCOME MEASURES: Incidence of DSCH, risk
      factors associated with its occurrence, visual outcomes, and factors important
      for prognosis. RESULTS: Of a total of 2285 glaucoma filtration procedures, 66
      (2.9%) cases of DSCH were identified. It developed in 9 of 615 (1.5%)
      trabeculectomies without antimetabolite, 30 of 1248 (2.4%) trabeculectomies with
      antimetabolite, 2 of 72 (2.8%) valved tube shunt implantations, and 25 of 350
      (7.1%) nonvalved tube shunt implantations. The increased incidence of DSCH after
      tube shunts compared with trabeculectomy-associated DSCH was significant (P <
      0.0001) with an odds ratio of 3.2. The risk factors for DSCH after glaucoma
      surgery include white race (P = 0.012), anticoagulation (P = 0.034), severe
      postoperative hypotony (P = 0.033), and aphakia/anterior chamber intraocular lens
      (P = 0.002). The visual outcomes of patients with hemorrhage were poor, with a
      decrease in logarithm of the minimum angle of resolution visual acuity from 0.72
      to 1.36, which was statistically significant compared with the controls (P <
      0.009). CONCLUSIONS: Delayed suprachoroidal hemorrhage occurs more frequently
      after tube shunt implantation than after trabeculectomy. Caution should be
      exercised when operating on patients with known risk factors, because the visual
      outcomes after DSCH are poor.

PMID- 11581054
TI  - Using optical imaging summary data to detect glaucoma.
AB  - PURPOSE: To evaluate the sensitivity and specificity for discriminating between
      early to moderate glaucomatous and normal eyes using summary data reports from
      the Heidelberg Retina Tomograph (HRT), the GDx Nerve Fiber Analyzer (GDx), and
      the Optical Coherence Tomograph (OCT). DESIGN: Comparative cross-sectional study
      PARTICIPANTS: One eye each of 50 normal subjects and 39 glaucoma patients with
      early to moderate visual field damage (mean deviation, -5.04 +/- 3.32 dB; range, 
      0.85 to -13.2 dB). METHODS: Three experienced graders masked to patient identity
      and diagnosis evaluated each summary data report from the HRT, GDx, and OCT
      independently. MAIN OUTCOME MEASURES: Each summary report was classified as
      either normal or glaucomatous. Sensitivity and specificity are reported for each
      grader, and agreement between graders is reported. RESULTS: For the HRT,
      sensitivity and specificity ranged from 64% to 75% and 68% to 80%, respectively.
      Agreement (kappa +/- standard error [SE]) between observers one and two, two and
      three, and one and three was 0.73 +/- 0.07, 0.77 +/- 0.07, and 0.67 +/- 0.08,
      respectively. For the GDx, sensitivity and specificity ranged from 72% to 82% and
      56% to 82%, respectively. Agreement (kappa +/- SE) between observers one and two,
      two and three, and one and three was 0.66 +/- 0.08, 0.66 +/- 0.08, and 0.50 +/-
      0.09, respectively. For the OCT, sensitivity and specificity ranged from 76% to
      79% and 68% to 81%, respectively. Agreement (kappa +/- SE) between observers one
      and two, two and three, and one and three was 0.73 +/- 0.07, 0.58 +/- 0.08, and
      0.51 +/- 0.09, respectively. CONCLUSIONS: When used alone, HRT, GDx, and OCT
      summary data reports can differentiate between normal and glaucomatous eyes with
      mild to moderate visual field loss. However, none of the instruments provided
      sensitivity and specificity that justify summary data reports being used as a
      screening tool for early to moderate glaucoma.

PMID- 11581055
TI  - Clinical profile and outcome in Bacillus endophthalmitis.
AB  - OBJECTIVE: To study the clinical presentation, microscopic and organismal culture
      correlation of vitreous, and species-specific outcome in Bacillus endophthalmitis
      DESIGN: Retrospective noncomparative case series. INTERVENTION: Thirty-one
      culture proven Bacillus endophthalmitis patients between January 1991 and
      February 1998 underwent vitrectomy and intravitreal antibiotic injection.
      Lensectomy was combined when considered essential, and on a few occasions
      intravitreal dexamethasone was added. The patients also received topical and
      systemic antibiotics. The undiluted vitreous biopsy was the source for
      microbiologic evaluation (microscopy and culture sensitivity). MAIN OUTCOME
      MEASURES: The duration of symptoms, the presenting visual acuity, and influence
      of intravitreal dexamethasone with intravitreal antibiotics were examined for any
      statistical correlation with the final visual acuity. RESULTS: Trauma was the
      major cause of infection. Vitreous biopsy microscopy demonstrated gram-positive
      bacillus in 28 of 31 cases, and polymicrobial infection was seen in 12 instances.
      All Bacillus species were sensitive to gentamicin, followed by vancomycin and
      ciprofloxacin. Clinical treatment within 7 days of symptoms, use of intravitreal
      vancomycin, and absence of polymicrobial infection were associated with better
      visual outcome. CONCLUSIONS: With appropriate treatment that essentially consists
      of vitrectomy and intravitreal antibiotics, patients with Bacillus
      endophthalmitis are likely to benefit in many instances. Gram-positive bacilli
      detected on vitreous microscopy should be empirically treated as Bacillus species
      unless otherwise proved.

PMID- 11581056
TI  - An in vitro resistance study of levofloxacin, ciprofloxacin, and ofloxacin using
      keratitis isolates of Staphylococcus aureus and Pseudomonas aeruginosa.
AB  - PURPOSE: We compared levofloxacin with ciprofloxacin and ofloxacin using the in
      vitro susceptibilities of Staphylococcus aureus (SA) and Pseudomonas aeruginosa
      (PA) keratitis isolates. DESIGN: Retrospective, clinical laboratory study of
      antibiotic susceptibility among keratitis isolates. PARTICIPANTS: Keratitis
      isolates from 200 patients with either SA or PA keratitis. METHODS: Minimum
      inhibitory concentrations (MICs) were determined for levofloxacin, ofloxacin, and
      ciprofloxacin for 93 SA keratitis isolates (68 fluoroquinolone-resistant and 25
      susceptible, as determined by disk diffusion) and 107 PA keratitis isolates (13
      fluoroquinolone-resistant and 94 susceptible). National Committee for Clinical
      Laboratory Standards susceptibilities were determined and analyzed statistically.
      Time kill studies were determined for fluoroquinolone-susceptible and -resistant
      isolates to all antibiotics at 8 microg/ml. The killing rates were determined by
      regression, and the colony count decreases were analyzed. MAIN OUTCOME MEASURES:
      The susceptibilities and potencies of levofloxacin, ciprofloxacin, and ofloxacin
      to SA and PA were determined from the MICs. Time kill studies determined the
      killing rates and decreases in colony counts. RESULTS: The fluoroquinolone
      resistant SA susceptibilities to levofloxacin, ofloxacin, and ciprofloxacin were
      only 22%, 10%, and 3%, respectively. The fluoroquinolone-susceptible SA were 100%
      susceptible to all antibiotics, with levofloxacin demonstrating the best potency.
      The fluoroquinolone-resistant PA were resistant to all antibiotics. The
      fluoroquinolone-susceptible PA isolates were highly susceptible to levofloxacin,
      ofloxacin, and ciprofloxacin, with ciprofloxacin demonstrating the highest
      potency. For fluoroquinolone-susceptible SA and PA, the time kill studies
      determined that the killing rates and decreases in colony counts were equivalent
      for all three antibiotics tested. The time kill studies demonstrated no colony
      count decreases for the fluoroquinolone-resistant SA and PA. CONCLUSIONS: Taken
      together, our susceptibility and time kill data failed to demonstrate convincing
      differences in the susceptibility of SA and PA keratitis isolates to
      levofloxacin, ciprofloxacin, and ofloxacin. In general, bacterial isolates that
      were resistant to ciprofloxacin and ofloxacin were also resistant to
      levofloxacin.

PMID- 11581057
TI  - Bacillus cereus keratitis associated with contact lens wear.
AB  - OBJECTIVE: We report the first case of contact lens-related Bacillus cereus
      keratitis and ulcer associated with B. cereus contamination of the contact lens
      case. This is also the first study to investigate and establish the genetic
      identity of an organism isolated from the cornea and contact lens case in a
      patient with contact lens-associated keratitis. DESIGN: Case report. INTERVENTION
      AND TESTING: Conjunctival swabs and corneal scrapings from the left eye were
      inoculated for culture. The contact lens case was also cultured. Antibiotic
      susceptibility testing was determined by agar disk diffusion method. Initial
      treatment with topical ciprofloxacin and fortified tobramycin was given. Genetic
      analysis of the bacterial isolates was performed using polymerase chain reaction
      (PCR) with enterobacterial repetitive intergenic consensus primers (ERIC; ERIC
      PCR). Susceptibility of B. cereus to heat and contact lens disinfecting solutions
      containing hydrogen peroxide, hydrogen peroxide-catalase, polyquaternium-1, and
      polyaminopropyl biguanide (PAPB) was tested. MAIN OUTCOME MEASURES: Clinical
      features, culture results, and antibiotic susceptibility testing were analyzed.
      The ERIC-PCR amplification products were visualized in ethidium bromide-stained
      agarose gel. Bacterial growth after exposure to heat and contact lens
      disinfecting solutions was assessed on blood agar plates. RESULTS: B. cereus was
      grown from the conjunctiva, corneal ulcer, and contact lens case. All isolates
      were sensitive to gentamicin, tobramycin, ciprofloxacin, clindamycin, and
      vancomycin. The corneal ulcer gradually healed over the next 6 days. Results of
      ERIC-PCR showed that the isolates from the cornea and contact lens case were
      indistinguishable, thus demonstrating the source of infecting organism to be the
      contaminated contact lens case. Exposure to a temperature of 80 degrees C for 20
      minutes and incubation with hydrogen peroxide-catalase, polyquaternium-1, and
      PAPB for the minimum recommended time failed to kill B. cereus. Only exposure to
      hydrogen peroxide for 4 hours eradicated the organism. CONCLUSIONS: B. cereus
      should be considered a possible etiologic agent of contact lens-associated
      keratitis. Heat and many types of contact lens disinfecting solutions may be
      ineffective in eradicating B. cereus from contaminated contact lens cases. Only
      prolonged exposure to hydrogen peroxide appeared to be sporicidal to B. cereus in
      this study.

PMID- 11581058
TI  - Iatrogenic complications related to the use of Herrick Lacrimal Plugs.
AB  - PURPOSE: To report a series of lacrimal complications associated with a specific
      type of lacrimal plug (Herrick Lacrimal Plug; Lacrimedics Incorporated, Rialto,
      CA.) DESIGN: Retrospective, noncomparative case series and survey. METHODS:
      Members of the American Society of Ophthalmic Plastic and Reconstructive Surgery
      were asked to submit personally treated cases of patients referred for treatment
      of complications after placement of a Herrick Lacrimal Plug. MAIN OUTCOME
      MEASURES: Failure of the device to be removed by simple lacrimal irrigation.
      RESULTS: The clinical courses of 41 patients were analyzed. Patients ranged in
      age from 19 to 81 years, and all had symptomatic epiphora related to the presence
      of the lacrimal plug. Several interventions were used to treat lacrimal
      obstruction. Nasolacrimal duct probing with irrigation was used in 15 lacrimal
      systems, whereas six systems were probed and subsequently stented with silicone
      tubing. Eyelid margin cutdown was used in eight cases. Balloon dacryoplasty was
      performed in three systems, dacryocystorhinostomy in 18 instances, and
      conjunctivodacryocystorhinostomy in two patients. CONCLUSIONS: The Herrick
      lacrimal occlusion device sometimes cannot be removed by simple irrigation and is
      capable of inducing permanent, irreversible, symptomatic lacrimal drainage system
      obstruction.

PMID- 11581059
TI  - Tacrolimus (FK506) in the management of high-risk corneal and limbal grafts.
AB  - OBJECTIVE: To assess the efficacy and side effects of tacrolimus in the
      management of patients with high-risk corneal and limbal grafts. DESIGN:
      Noncomparative case series. PARTICIPANTS: Seventeen patients (23 grafts) were
      treated with tacrolimus; 15 patients (20 host corneas) had two or more quadrants
      of stromal vascularization, 6 patients had stem cell deficiency, and 6 patients
      had glaucoma. Seven patients had received one previous graft, six patients had
      two previous grafts, and four patients had three previous grafts. INTERVENTION:
      Patients with high-risk corneal and limbal grafts were treated with systemic
      tacrolimus at a mean optimum dosage of 4.4 mg daily (range, 2-12 mg daily). MAIN
      OUTCOME MEASURES: Graft survival, visual acuity. RESULTS: No patient has had
      irreversible graft rejection while receiving tacrolimus. The follow-up period
      ranges from 12 to 46 months, with a mean of 24 months. Three patients have had
      reversible graft rejection associated with low tacrolimus levels. Nine patients
      have stopped treatment; two had reversible rejection within 2 months of stopping,
      and five grafts remain clear. The other four patients stopped treatment because
      of graft failure, which was not considered to be rejection related. Eight
      patients remain on treatment, and all have clear grafts. CONCLUSIONS: Tacrolimus
      (FK506) is effective in prevention of rejection in patients with high-risk
      corneal and limbal grafts.

PMID- 11581060
TI  - Effect of hinged lamellar keratotomy on postkeratoplasty eyes.
AB  - PURPOSE: To evaluate the effect of a hinged lamellar keratotomy on refraction,
      vision, and corneal topography of postkeratoplasty eyes with high-degree
      astigmatism. DESIGN: Noncomparative, interventional case series. PARTICIPANTS: A
      hinged lamellar keratotomy was performed on nine eyes of nine patients at least 9
      months after penetrating keratoplasty and with high-degree astigmatism. All
      patients were spectacle and contact lens intolerant. INTERVENTION: A superiorly
      hinged lamellar keratotomy (corneal flap), 160 microm in thickness and 9 mm in
      diameter, was created on all eyes included in this study. Each patient was
      examined 1 day, 1 month, and 3 months after surgery. MAIN OUTCOME MEASURES:
      Uncorrected visual acuity, best spectacle-corrected visual acuity, refraction,
      computerized analysis of corneal topography. RESULTS: At each postoperative
      examination time, there was a significant reduction in both average spherical
      equivalent (P < 0.05) and average absolute value of astigmatism (P < 0.01) over
      mean preoperative values. The major changes were seen as early as 1 day after
      surgery, but both progression and regression of the effect were documented at
      later postoperative examinations. In all patients best spectacle-corrected acuity
      was maintained or improved after the procedure. Postoperatively, four patients
      could be successfully corrected either with spectacles (n = 2) or with gas
      permeable contact lenses (n = 2). There were no surgical flap or corneal graft
      complications. CONCLUSIONS: Hinged lamellar keratotomy improves vision and
      refraction of postkeratoplasty eyes with high-degree astigmatism. In some cases
      it may be so effective as to make planned excimer laser treatment unnecessary.

PMID- 11581062
TI  - Human immunodeficiency virus-positive patients with posterior intracorneal
      precipitates.
AB  - PURPOSE: To describe an unusual and possibly new keratopathy in human
      immunodeficiency virus (HIV)-positive patients. DESIGN: Retrospective
      observational case series. PARTICIPANTS: : Six HIV-positive patients at four
      centers. METHODS: A complete medical history was obtained and a thorough
      ophthalmic examination was performed on each of the patients. RESULTS: Each
      patient had bilaterally symmetrical keratopathy consisting of variably pigmented
      round and reticular posterior intracorneal precipitates at the level of
      Descemet's membrane. The precipitates were diffuse, but larger and more prominent
      near the limbus and finer toward the central cornea. None of the eyes were
      inflamed, and all had normal vision. No patient had uveitis on presentation or
      any history of cytomegalovirus retinitis. CONCLUSION: These patients have a
      unique posterior keratopathy, which requires further investigation.

PMID- 11581063
TI  - Therapeutic lamellar keratoplasty for limbal dermoids.
AB  - PURPOSE: To assess the surgical outcomes of appearance, vision, refraction, and
      graft survival and integrity in patients with histologically proven limbal
      dermoid choristomata who underwent lamellar keratoplasty. DESIGN: Retrospective
      noncomparative analysis of a consecutive case series with patient recall and
      examination. PARTICIPANTS: Eleven patients (six female, five male, median age,
      9.6 years; range, 1-29 years) with 12 limbal dermoids in 11 eyes operated on
      between 1995 and 1998 were identified from the eye bank database at the Singapore
      National Eye Centre. METHODS: Case records, photographs, and eye bank data were
      examined. Patients not already seen by the authors within the previous 3 months
      were recalled and examined. OUTCOME MEASURES: Descriptive data: size and location
      of the dermoid, presence of lipid keratopathy; visual acuity; refraction and
      astigmatism, vector analysis, surgically induced refractive change; corneoscleral
      and limbal match, haze, vascularity; graft integrity, clarity, vascularization,
      and rejection episodes. RESULTS: Most (7 of 11) patients had single
      inferotemporal limbal dermoids, although one patient had two dermoids in one eye.
      Median follow-up time was 21.6 months (range, 9.0-46.4 months). Most (8 of 11)
      patients had good or excellent cosmetic results with minimal interface haze and
      no vascularization. Two cases with previously excised lesions had postoperative
      vascularization develop. One of these cases had graft infection develop,
      underwent subsequent debridement, and has an opaque graft. Best-corrected visual
      acuity was maintained or slightly improved in 9 of 11 patients. For the group and
      most individual patients, mean astigmatism, spherical equivalent, and refraction,
      as assessed by surgically induced refractive change and h-vector analysis, were
      not significantly changed. CONCLUSION: Lamellar keratoplasty as primary surgery
      for limbal dermoids gave good cosmetic results. However, improvement in
      refractive, astigmatic, and visual status is not guaranteed, and these procedures
      should be viewed more cautiously, although established good vision was maintained
      in our series.

PMID- 11581064
TI  - Third (fourth and fifth) nonocular tumors in survivors of retinoblastoma.
AB  - OBJECTIVE: This study aimed to investigate the incidence, timing, pattern, and
      distribution of, as well as survival as a result of, third, fourth, and fifth
      primary tumors in survivors of retinoblastoma. DESIGN: This study was a
      retrospective case series of patients diagnosed with retinoblastoma and a second
      malignant neoplasm. Records were examined for demographic, prior treatment, and
      second tumor information, as well as any evidence of the development of a third,
      fourth, or fifth nonocular tumor. When possible, telephone inquiries were
      conducted for follow-up. PARTICIPANTS: The study included 1506 patients followed
      in the Ophthalmic Oncology Center at New York-Presbyterian Hospital, New York
      Weill Cornell Medical Center, 211 of whom developed a second tumor and had
      sufficient treatment data to be useful for analysis. MAIN OUTCOME MEASURES: The
      development of third and additional nonocular tumors and survival from these
      tumors were the primary outcome measures. RESULTS: Of 211 second-tumor patients,
      142 died before an additional malignancy developed (median survival time, 1.8 +/-
      0.3 years) and in 28, third tumors developed (5-year incidence rate, 11%; 10-year
      incidence rate, 22%; median time to third tumor development, 5.8 +/- 8.3 years).
      The 5- and 10-year survival rates for this group were 41% and 30%, respectively
      (median survival time, 4.1 +/- 1.0 years). Of 28 patients in whom third tumors
      developed, 27 (96%) had received radiation therapy for their retinoblastoma. The
      most common sites for third tumors were soft tissues of the head (36% of all
      third tumors) and skin (36% of all third tumors). In six patients, a fourth tumor
      developed, and in two patients a fifth tumor developed. All fourth and fifth
      tumors were found in the soft tissues of the head, the skin, or the bones.
      CONCLUSIONS: Survivors of retinoblastoma in whom second malignant neoplasms
      develop are at a higher risk for the development of additional tumors than they
      were for the development of a second tumor. The locations and expected ages at
      which additional tumors develop are consistent with the patterns we have seen in
      second tumors.

PMID- 11581065
TI  - Outcome of patients with periocular sebaceous gland carcinoma with and without
      conjunctival intraepithelial invasion.
AB  - PURPOSE: To evaluate the clinical findings, histopathologic features, methods of
      management, and outcomes in 25 patients with eyelid sebaceous gland carcinoma
      with and without conjunctival intraepithelial (pagetoid) invasion. PARTICIPANTS:
      Twenty-five patients with sebaceous gland carcinoma of the periocular region.
      DESIGN: Retrospective, observational case series. METHODS: The patients were
      divided into two groups: group A included those with sebaceous gland carcinoma
      with conjunctival intraepithelial (pagetoid) invasion, and group B included those
      with sebaceous gland carcinoma without conjunctival intraepithelial invasion. The
      demographic, clinical, and histopathologic features of sebaceous gland carcinoma
      were reviewed separately for each group. Ocular management results and systemic
      prognosis were reviewed. RESULTS: Of the 25 patients, 18 (72%) were females and 7
      (28%) were males. The mean age at diagnosis was 65 years (range, 17-90 years).
      There were 11 patients (44%) in group A, and 14 (56%) in group B. The most common
      symptom in group A was ocular irritation (45%), and in group B the most common
      symptom was eyelid lump (86%). The most common sign in group A was diffuse eyelid
      thickening (72%), and in group B the most common sign was a distinct eyelid mass
      (43%). Six patients (55%) in group A, compared with one patient (7%) in group B,
      had both upper and lower eyelid involvement. The most frequent location of tumor
      epicenter was the outer third of the eyelid in both groups: 37% in group A and
      57% in group B. Histopathologic origin of tumor was multicentric in four patients
      (36%) of group A and six patients (50%) of group B. Before referral, local
      recurrence had been found in 4 of 12 patients (33%) who underwent surgical
      treatment elsewhere. After referral, local recurrence was detected in 1 patient
      (9%) in group A and in 2 patients (14%) in group B. Orbital exenteration was
      necessary in 4 patients (36%) in group A and in one patient (7%) in group B.
      Tumor-related metastases occurred in two patients (18%) in group A and in two
      patients (14%) in group B. CONCLUSIONS: Sebaceous gland carcinoma with
      conjunctival intraepithelial (pagetoid) invasion has different clinical features
      compared with that without pagetoid invasion. Conjunctival intraepithelial
      (pagetoid) invasion carries a higher risk for orbital exenteration, but the risk
      of tumor-related metastases is similar in both groups.

PMID- 11581066
TI  - Orbital involvement in cherubism.
AB  - PURPOSE: To demonstrate the clinical, radiologic, and histopathologic features of
      a patient with orbital involvement in cherubism that prompted surgical treatment.
      DESIGN: Single interventional case report. INTERVENTION: Findings of the
      ophthalmic evaluation, computed tomography (CT) scans, intraoperative
      examination, and light microscopy of the specimens were analyzed. MAIN OUTCOME
      MEASURES: Globe displacement, orbital bony lesions detected on CT scans,
      histopathology, and postoperative results were assessed. RESULTS: A 27-year-old
      female was seen with a slowly progressive superonasal globe displacement and a
      temporal orbital mass bilaterally of 6 years' duration. She had a history of
      cherubism, but her cheeks and jaws had a normal appearance instead of the
      bilateral fullness of the lower half of the face typical of the disease. CT scans
      demonstrated multicystic bony lesions arising from the orbital floors
      bilaterally. The masses were excised using an anterior transcutaneous transseptal
      orbitotomy. Histopathology demonstrated numerous giant cells in a fibrovascular
      stroma, confirming the clinical diagnosis of cherubism. Postoperative recovery
      was complete. CONCLUSIONS: Orbital involvement in cherubism may develop beyond
      puberty, after stabilization or regression of the lesions in the jaws. Patients
      with cherubism should be routinely evaluated by an ophthalmologist.

PMID- 11581067
TI  - A simplified technique of ptosis repair using a single adjustable suture.
AB  - PURPOSE: To describe a simplified technique for ptosis repair using a single
      adjustable suture. DESIGN: Retrospective noncomparative series. PARTICIPANTS:
      Fifty-one cases of ptosis repair performed or supervised by the same surgeon
      between 1993 and 1995. INTERVENTION: The surgical approach consisted of using a
      single adjustable "hang-back" 5-0 silk suture for plication of the superior
      portion of the levator aponeurosis. Lid height was then reassessed within the
      first 4 postoperative days and permanently readjusted by fixating the adjustable
      suture. Excluded were patients with history of unstable ptosis as a result of
      systemic disease or congenital, mechanical, and traumatic ptosis resulting from a
      mass or trauma. The follow-up period ranged from 3 to 31 months. MAIN OUTCOME
      MEASURE: Lid position. RESULTS: All eyelids included in this study were corrected
      to 1 mm of the desired result. There were no incidents of peaking or recurrence
      on long-term follow-up. Complications included one case of hematoma and a case of
      slight tenting of the eyelid margin. CONCLUSIONS: This procedure combines the
      physiologic approach of levator aponeurosis surgery with the simplicity and
      flexibility of a single adjustable "hang-back" type suture. It may readily be
      combined with other procedures such as blepharoplasty. It is also useful when the
      "ideal" lid level may not be determined until the postoperative period, such as
      eyes subject to ptosis by Hering's law, levator dehiscence, or those at increased
      potential risk for corneal exposure.

PMID- 11581068
TI  - Depression, visual acuity, comorbidity, and disability associated with age
      related macular degeneration.
AB  - OBJECTIVE: To examine (1) the prevalence of depressive disorders in community
      dwelling adults with advanced age-related macular degeneration (AMD) and (2) the
      relationship in this population between depression, visual acuity, the number of
      comorbid medical conditions, disability caused by vision loss as measured by the
      National Eye Institute-Vision Function Questionnaire (NEI-VFQ) and the vision
      specific Sickness Impact Profile (SIPV), and disability caused by overall health
      status as measured by the Sickness Impact Profile-68 (SIP). DESIGN: Analysis of
      cross-sectional baseline data from a randomized clinical trial. PARTICIPANTS:
      Participants were 151 adults aged 60 and older (mean age, 80 years) with advanced
      macular degeneration whose vision was 20/60 or worse in their better eye.
      METHODS: Subjects were interviewed using measures of depression, disability, and
      chronic medical conditions. Visual acuity was obtained. Nonparametric correlation
      analyses and linear regression analyses were performed. MAIN OUTCOME MEASURES:
      Structured Clinical Interview for DSM-IV (SCID-IV), Geriatric Depression Scale
      (GDS), NEI-VFQ, SIPV, and SIP. RESULTS: Of the participants, 32.5% (n = 49) met
      SCID-IV criteria for depressive disorder, twice the rate observed in previous
      studies of community-dwelling elderly. Over and above depression (GDS), visual
      acuity aided in prediction of the level of vision-specific disability (NEI-VFQ
      and SIPV). CONCLUSIONS: Depressive disorder is a significant problem for the
      elderly afflicted with advanced macular degeneration. Further research on
      psychopharmacologic and psychotherapeutic interventions for depressed AMD
      patients is warranted to improve depression and enhance functioning. Over and
      above depression, visual acuity aided in predicting vision-specific disability.
      Treatment strategies that teach patients to cope with vision loss should be
      developed and evaluated.

PMID- 11581070
TI  - Autologous plasmin enzyme in the surgical management of diabetic retinopathy.
AB  - PURPOSE: This is a pilot study to assess the use of autologous plasmin enzyme
      (APE) as an adjunct to vitreous surgery in eyes with advanced diabetic
      retinopathy. DESIGN: Prospective noncomparative interventional case series.
      PARTICIPANTS: Seven patients with advanced diabetic retinopathy selected at
      random from our practice population. METHODS: Seven eyes were treated with APE as
      an adjunct to standard vitreous surgery. Six eyes had macular tractional retinal
      detachments, and one eye had refractory macular edema. Three fellow eyes had
      standard vitreous surgery performed for macular tractional retinal detachments
      without APE. All 10 eyes had macular edema and background diabetic retinopathy.
      MAIN OUTCOME MEASURES: The main outcome measures included induction of a
      posterior vitreous detachment, retinal reattachment, improvement in visual
      acuity, and resolution of macular edema. RESULTS: All seven APE-treated eyes
      achieved spontaneous or easy removal of the posterior hyaloid including one eye
      that had vitreoschisis over areas of detached retina. All eyes treated with APE
      had resolution of intraretinal edema. Retinas of all eyes treated with APE were
      reattached. The three fellow eyes were treated by vitreous surgery without APE.
      Two of the three fellow eyes had reattached retinas, but none had resolution of
      intraretinal edema without further focal photocoagulation treatment. Mean visual
      acuity improvement was 0.7 logarithm of the minimum angle of resolution (LogMAR)
      units in APE-treated eyes and 0.1 LogMAR units in eyes without APE. The average
      follow-up period was 14 months. CONCLUSIONS: This pilot study suggests that APE
      may be beneficial in the surgical management of diabetic retinopathy.

PMID- 11581072
TI  - Retinal capillary hemangioma: a comparison of sporadic cases and cases associated
      with von Hippel-Lindau disease.
AB  - OBJECTIVE: To report observations regarding the onset of tumors in patients with
      retinal capillary hemangiomas (RCH) and comparing sporadic cases with those
      associated with von Hippel-Lindau (VHL) disease. DESIGN: Retrospective
      consecutive case series. PARTICIPANTS: Sixty-eight patients with RCH managed at a
      tertiary referral center. MAIN OUTCOME MEASURES: The data were analyzed for age
      at diagnosis of RCH, two-hit mutation model, onset of new tumors, and random
      (Poisson) distribution. RESULTS: Among 68 patients, we identified 174 RCHs in 86
      eyes. Thirty-one patients had VHL disease, and 37 patients were sporadic. The
      median age at diagnosis in cases with VHL disease was 17.6 years (range, 2.8-46.7
      years), and in those without VHL disease it was 36.1 years (range, 7.0-74 years).
      The age distribution of RCH followed a two-hit mutation model. In eyes with VHL
      disease, the total number of RCH were distributed randomly as calculated by the
      Poisson distribution (mean number of tumors = 4). Overall onset of 33 new tumors
      was documented in 11 eyes (13%) over a median interval of 16 months (range, 3-235
      months). All new tumors developed before the age of 47 years. The retinal
      location of new tumors was similar to the previous tumors with most new tumors
      located in the superotemporal quadrant (42%) and in the midperipheral retina
      (58%). Of the 50 patients initially manifesting solitary RCH, only 4 had new
      tumors develop over a median follow-up duration of 6.4 years (range, 0-33 years).
      All four cases had VHL disease. CONCLUSIONS: The median age at diagnosis of RCH
      in patients with VHL disease was almost 18 years less than those without VHL
      disease. The age distribution of RCH followed the two-hit mutation model. In VHL
      disease, the number of RCH is determined randomly. Most of the new RCH develop by
      the age of 47 years. In the absence of VHL disease, it is unlikely for patients
      with solitary RCH to develop new tumors.

PMID- 11581073
TI  - Renal coloboma syndrome.
AB  - OBJECTIVE: To characterize the ocular features of renal coloboma syndrome.
      DESIGN: Prospective, observational case series. PARTICIPANTS: Twelve patients
      referred by the pediatric nephrology clinic and the ophthalmic records of five
      additional patients. METHODS: For each patient, age at the time of examination,
      gender, renal function, and presence of a mutation in the PAX2 gene were noted.
      All patients underwent measurement of visual acuity and anterior and posterior
      segment examination with fundus photography. Goldmann visual fields were tested
      in four cases. MAIN OUTCOME MEASURES: Visual acuity, optic disc abnormalities,
      and mutation in the PAX2 gene. RESULTS: Mean age was 21.5 years. Renal failure
      was mild in 6 patients and severe in 11 patients. A mutation in the PAX2 gene was
      identified in nine patients, without correlation to the ocular phenotype. Ocular
      features could be divided into five groups: optic disc dysplasia limited to an
      unusual pattern of retinal vessels without functional consequence; optic disc pit
      with normal visual acuity and blind spot enlargement; large optic disc coloboma;
      large coloboma of the optic disc and adjacent retina; morning glory anomaly
      (these last three conditions were accompanied by poor visual acuity). Fundus
      abnormalities were symmetrical in most cases and unrelated to renal status.
      CONCLUSIONS: Ophthalmic and renal characteristics of the renal coloboma syndrome
      are highly variable. The need for dialysis or renal transplantation can occur
      early in life or several years later. A wide range of ocular abnormalities
      located in the posterior segment can be observed. Mild optic disc dysplasia or
      pit have no functional consequence and can be underdiagnosed. More severe
      colobomas or related abnormalities, such as morning glory anomaly, often lead to
      poor visual acuity. Molecular biology allows detection of the mutations in the
      PAX2 gene, but can be negative in approximately 50% of cases. The observation of
      an optic disc coloboma or related abnormality stimulates the ophthalmologist to
      propose simple nephrologic investigations to check for renal hypoplasia, a
      potentially life-threatening disease. Conversely, renal hypoplasia stimulates the
      nephrologist to ask for a fundus examination to confirm the diagnosis and check
      for complications such as retinal detachment.

PMID- 11581074
TI  - Nyctalopia in antiquity: a review of the ancient Greek, Latin, and Byzantine
      literature.
AB  - OBJECTIVE: To investigate the original definition and use of the term nyctalopia
      in ancient medical literature in view of the controversy between the English and
      some continental European literatures. DESIGN: Historical manuscript. METHODS: We
      review the use of the term in ancient Greek, Roman, and early Byzantine medical
      literature (5th century BC-7th century AD) and include a quick reference to the
      theories on its etymology. RESULTS: Physicians of antiquity defined as nyctalopia
      the symptom of defective dark adaptation, most commonly in the clinical setting
      of vitamin A deficiency. An alternative definition, the improvement of vision at
      night, is not recorded before the 2nd century AD and seems to result from a
      broader interpretation of the word, lacking medical acceptance at that time.
      CONCLUSIONS: We propose to the ophthalmic community the use of the term
      nyctalopia exclusively for the description of defective dark adaptation.

PMID- 11581075
TI  - Intrastromal corneal ring segments for low myopia: a report by the American
      Academy of Ophthalmology.
AB  - OBJECTIVE: This document describes intrastromal corneal ring segments (Intacs)
      inserts technology and examines the evidence to answer the key question about
      whether the treatment is safe and effective in correcting low myopia. METHODS: A
      literature search that was conducted in September 2000 retrieved 13 relevant
      citations, and the reference lists of these articles were consulted for
      additional citations. Panel members reviewed this information and articles were
      rated according to the strength of evidence. RESULTS: Prospective multicenter
      phase II and III clinical trials (Level II evidence rating) of Intacs inserts for
      myopia of -1.00 to -3.00 diopters (D), with a maximum of +1.00 D of astigmatism,
      enrolled a total of 452 subjects, with a total of 454 surgical attempts. The
      results from phase II and phase III were pooled for much of the analysis. At 1
      year, 97% of patients who completed follow-up had 20/40 or better uncorrected
      visual acuity (UCVA). Seventy-four percent of patients had 20/20 or better UCVA.
      Ninety-two percent of eyes were within +/-1 D of intended refractive correction,
      and 69% were within 0.5 D of intended refractive correction. At 3 months, 90% of
      patients had less than 1.0 D of change from the previous examination performed at
      1 month. The ocular complication rate, which was defined as clinically
      significant events but not resulting in permanent sequelae, was 11% at 12 months.
      The adverse event rate was 1.1%, defined as a serious event if untreated. Nearly
      9% of patients requested to have their inserts removed and a total of 3.8% of
      patients required a secondary surgical intervention. CONCLUSIONS: To date,
      evidence suggests that low myopia (-1 to -3 D) in a well-defined group of
      patients who have a stable manifest refraction and less than +1.0 D of
      astigmatism can be treated with Intacs inserts with a reasonable assurance of
      safety and effectiveness. Additional clinical research is needed to determine the
      long-term effectiveness of treatment and the comparative safety, effectiveness,
      and costs with other treatment modalities, including laser-assisted in-situ
      keratomileusis (LASIK) and photorefractive keratectomy (PRK).

PMID- 11581076
TI  - Post-resuscitative hypothermic bypass reduces ischemic brain injury in swine.
AB  - OBJECTIVES: Increasing human and laboratory evidence suggests that post
      resuscitative brain hypothermia reduces the pathologic consequences of brain
      ischemia. Using a swine model of prolonged cardiac arrest, this investigation
      sought to determine whether unilateral hypothermic carotid bypass was capable of
      inducing selective brain hypothermia and reducing neurohistologic damage.
      METHODS: Ventricular fibrillation was induced in common swine (n = 12). After 20
      minutes of cardiopulmonary arrest (without ventilatory support or cardiopulmonary
      resuscitation), systemic extracorporeal bypass was instituted to restore coronary
      and cerebral perfusion, followed by restoration of normal sinus rhythm. Animals
      randomized to the normal brain temperature (NBT) cohort received mechanical
      ventilation and intravenous fluids for 24 hours. The selective brain hypothermia
      (SBH) cohort received 12 hours of femoral/carotid bypass at 32 degrees C. The
      bypass temperature was then increased one degree per hour until reaching 37
      degrees C and continued at this temperature until completion of the protocol (24
      hours). Histopathologic damage was evaluated in two areas of the hippocampus.
      RESULTS: Normal sinus rhythm was restored in all animals after the systemic
      (femoral/femoral) bypass was initiated. Nasal temperature (surrogate measure of
      brain temperature) remained higher than 37.0 degrees C throughout the 24-hour
      recovery period in the NBT animals. In the SBH cohort, right nasal temperature
      dropped to the mild hypothermic range (<34 degrees C) two hours after institution
      of femoral/carotid bypass. This was maintained throughout the 12-hour cooling
      period without hemodynamic compromise. There was a significant improvement in the
      neurohistology scores in the CA1 region of the hippocampus of the SBH treated
      animals as compared with those of the NBT cohort. CONCLUSIONS: Post-resuscitative
      selective brain hypothermia reduced regional ischemic brain damage in swine with
      prolonged ventricular fibrillation.

PMID- 11581077
TI  - Anti-interleukin-6 antibodies attenuate inflammation in a rat meningitis model.
AB  - OBJECTIVES: Interleukin-6 (IL-6) is elevated in the cerebrospinal fluid (CSF) of
      humans and animals with bacterial meningitis. This study's hypothesis was that
      anti-IL-6 antibodies will attenuate meningeal inflammation in a rat model of
      bacterial meningitis. METHODS: 14 male Sprague-Dawley rats were inoculated
      intracisternally (IC) with 0.1 mL of heat-killed pneumococci. At one hour post
      inoculation, the rats received intraperitoneal doses of either 1.0 mL phosphate
      buffered saline (PBS treatment group, n = 7) or 70 microg anti-IL-6 antibodies in
      1.0 mL PBS (anti-IL-6 antibody treatment group, n = 7). Nine rats (normal group,
      n = 9) had no inoculation, and four rats (surgical sham group, n = 4) had IC
      inoculations of saline. At six hours post-inoculation, all the animals had CSF
      removed via IC tap. The CSF protein and white blood cell (WBC) count measures
      were compared using a t-test. RESULTS: Mean CSF WBC for the anti-IL-6 treatment
      group was 2,458/microL, versus the PBS controls' mean of 9,697/microL (p =
      0.007). Mean CSF protein for the anti-IL-6 group was 180 mg/dL, versus 296 mg/dL
      for the controls (p = 0.032). The surgical sham and normal animals had normal CSF
      WBC and protein values. CONCLUSIONS: In this rat meningitis model, systemic
      treatment with anti-IL-6 antibodies after the induction of meningitis suppressed
      both CSF WBC count and CSF protein level, two important indices of meningeal
      inflammation.

PMID- 11581079
TI  - Attenuation of verapamil-induced myocardial toxicity in an ex-vivo rat model
      using a verapamil-specific ovine immunoglobin.
AB  - OBJECTIVE: To determine whether an ovine verapamil-specific immunoglobin G (V
      IgG) attenuates verapamil toxicity in an ex-vivo rat left ventricular papillary
      muscle model. METHODS: The authors dissected left ventricular papillary muscle
      strips from male Sprague-Dawley rats (350-410 g) and suspended them in an oxygen
      perfused Tyrode buffer bath at 37.5 degrees C. Muscle strips equilibrated for 90
      minutes under electrical stimulation of 1 Hz. Resting and developed tension (mg)
      were monitored continuously. A concentration-response trial was performed with
      verapamil concentrations ranging from 31 to 1,020 nM; 510 nM produced consistent
      reduction in developed tension. A trial of V-IgG was then conducted by
      administering the following treatments to papillary muscle strips in a randomized
      manner: V-IgG + 510 nM verapamil, nonspecific ovine IgG (N-IgG) + 510 nM
      verapamil (protein control), and 510 nM verapamil alone. Immunoglobin G was
      administered in equimolar concentrations to verapamil. Attenuation was expressed
      as inhibition of the verapamil-induced reduction of developed tension. RESULTS:
      The V-IgG comparative trial indicated the V-IgG + verapamil treatment had a mean
      reduction in developed tension of 14.1% (SD +/- 12.2) compared with 36.2% (SD +/-
      14.9) for N-IgG + verapamil and 34.9% (SD +/- 8.1) for verapamil alone (p <
      0.05). There was no difference between the two control groups. CONCLUSION:
      Verapamil-specific IgG attenuated verapamil-induced reduction of developed
      tension in an ex-vivo rat model.

PMID- 11581080
TI  - Potassium repletion fails to interfere with reduction of serum lithium by sodium
      polystyrene sulfonate in mice.
AB  - OBJECTIVES: Previous studies have shown that oral sodium polystyrene sulfonate
      (SPS) lowers serum lithium concentrations after acute and chronic toxic lithium
      exposures. Because hypokalemia may represent a deterrent to the clinical use of
      SPS for lithium intoxication, this study was designed to determine whether
      potassium (K+) repletion interferes with the effect of SPS on serum lithium.
      METHODS: 168 male, CD-1 mice were given lithium chloride (LiCl) (250 mg/kg) by
      gavage at time 0. Half of the mice were then given SPS (5 g/kg/dose) and half an
      equivalent volume of water by gavage at times 20 and 40 minutes. Half of each of
      these subgroups was then given potassium chloride (KCl) (3 mmol/kg)
      intraperitoneally and half an equivalent volume of normal saline. The animals
      were then sacrificed at one, two, four, and eight hours after lithium
      administration and the sera were analyzed for lithium and K+ by atomic absorption
      spectrophotometry. The groups were compared with analysis of variance. RESULTS:
      The SPS lowered both lithium and K+ concentrations (ps < or = 0.0001). The KCl
      treatment was associated with transiently increased K+ concentrations (p <
      0.0001) and with mildly elevated lithium concentrations when compared with the
      results of the animals not treated with KCl (p = 0.0016). The KCl treatment
      associated increase in lithium concentration occurred both in the animals treated
      with water and in those treated with SPS. CONCLUSIONS: Potassium repletion did
      not interfere with the ability of SPS to lower serum lithium concentration in
      animals experimentally poisoned with lithium.

PMID- 11581081
TI  - Electrocardiographic ST-segment elevation: the diagnosis of acute myocardial
      infarction by morphologic analysis of the ST segment.
AB  - Acute myocardial infarction (AMI) is one of many causes of ST-segment elevation
      (STE) in emergency department (ED) chest pain (CP) patients. The morphology of
      STE may assist in the correct determination of its cause, with concave patterns
      in non-AMI syndromes and non-concave waveforms in AMI. OBJECTIVES: To determine
      the impact of STE morphologic analysis on AMI diagnosis and the ability of this
      technique to separate AMI from non-infarction causes of STE. METHODS: The
      electrocardiograms (ECGs) of consecutive ED adult CP patients (with three serial
      troponin I determinations) were interpreted in two-step fashion by six attending
      emergency physicians (EPs): 1) the determination of STE by three EPs followed by
      2) STE morphologic analysis (either concave or non-concave) in those patients
      with STE. The impact of STE morphology analysis was investigated in the
      identification of AMI and non-AMI causes of STE. Acute myocardial infarction was
      diagnosed by abnormal serum troponin I values (>0.1 mg/dL) followed by a rise and
      fall of the serum marker; STE diagnoses of non-AMI causes were determined by
      medical record review. Interobserver reliability concerning STE morphology was
      determined. Study inclusion criteria included at least three troponin values
      performed in serial fashion no more frequently than every three hours, initial ED
      ECG, ED diagnosis, and final hospital diagnosis. RESULTS: Five hundred ninety
      nine CP patients were entered in the study, with 171 (29%) individuals having STE
      on their ECGs. Of the 171 patients who had STE, 56 had AMI, 50 had unstable
      angina pectoris (USAP), and 65 had non-coronary final diagnoses. Forty-nine
      patients had non-concave STE, 46 with AMI and three with USAP; no patient with a
      non-coronary diagnosis had a non-concave STE morphology. The sensitivity and
      specificity of the non-concave STE morphology for AMI diagnoses were 77% and 97%,
      respectively; the positive and negative predictive values for non-concave
      morphology in AMI diagnoses were 94% and 88%, respectively. Interobserver
      reliability in the STE morphology determination revealed a kappa coefficient of
      0.87. CONCLUSIONS: A non-concave STE morphology is frequently encountered in AMI
      patients. While the sensitivity of this pattern for AMI diagnosis is not
      particularly helpful, the presence of this finding in adult ED chest pain
      patients with STE strongly suggests AMI. This technique produces consistent
      results among these EPs.

PMID- 11581083
TI  - Dispatcher assistance and automated external defibrillator performance among
      elders.
AB  - OBJECTIVES: Automated external defibrillators (AEDs) provide an opportunity to
      improve survival in out-of-hospital, ventricular fibrillation (VF) cardiac arrest
      by enabling laypersons not trained in rhythm recognition to deliver lifesaving
      therapy. The potential role of emergency dispatchers in the layperson use of AEDs
      is uncertain. This study was performed to examine whether dispatcher telephone
      assistance affected AED skill performance during a simulated VF cardiac arrest
      among a cohort of older adults. The hypothesis was that dispatcher assistance
      would increase the proportion who were able to correctly deliver a shock, but
      might require additional time. METHODS: One hundred fifty community-dwelling
      persons aged 58-84 years were recruited from eight senior centers in King County,
      Washington. All participants had received AED training approximately six months
      previously. For this study, the participants were randomized to AED operation
      with or without dispatcher assistance during a simulated VF cardiac arrest. The
      proportions who successfully delivered a shock and the time intervals from
      collapse to shock were compared between the two groups. RESULTS: The participants
      who received dispatcher assistance were more likely to correctly deliver a shock
      with the AED during the simulated VF cardiac arrest (91% vs 68%, p = 0.001).
      Among those who were able to deliver a shock, the participants who received
      dispatcher assistance required a longer time interval from collapse to shock
      [median (25th, 75th percentile) = 193 seconds (165, 225) for dispatcher
      assistance, and 148 seconds (138, 166) for no dispatcher assistance, p = 0.001].
      CONCLUSIONS: Among older laypersons previously trained in AED operation,
      dispatcher assistance may increase the proportion who can successfully deliver a
      shock during a VF cardiac arrest.

PMID- 11581084
TI  - The effect of written informed consent on detection of violence in the home.
AB  - Studies of programmatic interventions for victims of violence in the home may
      require the use of informed consent. The use of informed consent may result in
      ascertainment bias, with victims of violence being less likely to participate.
      OBJECTIVE: To investigate the effect of written informed consent on the detection
      of violence in the home during emergency department (ED) screening. METHODS: The
      authors performed a nonrandomized, controlled trial of 3,466 patients at an urban
      university ED. On odd days, patients (n = 1,857) were read a brief scripted
      statement and screened using standardized questions. On even days, patients (n =
      1,609) received standard written informed consent prior to the same screening
      questions (writ-IC). The main outcome was the number of cases of violence in the
      home detected using each screening protocol. RESULTS: Fewer writ-IC patients
      participated in screening (82% vs 92%; p < 0.001). Despite a higher refusal rate
      in the writ-IC group, there was no difference in the number of victims detected
      by each screening method: choked/kicked/bit/punched? (writ-IC, 7.3 vs routine
      screen, 6.5%; p = 0.3); slapped/grabbed/shoved? (7.3 vs 6.7%; p = 0.4);
      threatened/actually used knife/gun to scare/hurt you? (8.3 vs 9.4%; p = 0.3);
      thrown object to harm you? (5.2 vs 4.6%; p = 0.4); forced sex? (5.8 vs 4.7%; p =
      0.15); or afraid current/former intimate partner would hurt you physically? (13.9
      vs 11.9%; p = 0.9). CONCLUSIONS: A written informed consent process in screening
      for violence in the home is associated with a higher refusal rate than routine
      screening, but use of written informed consent does not result in a lower rate of
      detection for multiple forms of violence. The authors did not find any support
      for the hypothesis that the use of written informed consent would decrease
      detection of violence in the home.

PMID- 11581085
TI  - A comprehensive set of coded chief complaints for the emergency department.
AB  - OBJECTIVE: To develop a generally applicable set of coded chief complaints for
      the computerized patient records of emergency departments (EDs). METHODS: At an
      urban teaching ED the chief complaints of more than 50,000 patients were analyzed
      retrospectively during a 29-month period (June 1995-October 1997). Applying
      continuous quality improvement methods, a multidisciplinary team examined the
      current process documenting the patient's chief complaint. During two prospective
      periods (November 1997-December 1998; January 1999-June 1999), more than 34,000
      chief complaints were analyzed. To reduce free-text charting practices, a variety
      of interventions on individual and team level were applied. Quantitative analysis
      was performed with statistical process control charts, and a qualitative
      evaluation was performed with a questionnaire. RESULTS: The charting of chief
      complaint in free-text format decreased from 23% to 1%. The range among
      individual ED staff members narrowed from 45% to 9%. During the refinement of the
      set of coded chief complaints, six infrequently charted items were removed. Five
      new chief complaints identified by analysis of free-text entries during the
      second study period were added. The current set of chief complaints consists of
      54 codable and the three original free-text items. The ED staff members perceived
      all the interventions beneficial. A poster displaying all available terms as a
      visual aid, however, had the largest impact on charting the patient's chief
      complaint in coded format. CONCLUSIONS: Applying continuous quality improvement
      methods, the authors created a clinically developed and applicable set of codable
      chief complaints that can be easily integrated into a computerized patient record
      of an ED.

PMID- 11581086
TI  - Faculty triage shortens emergency department length of stay.
AB  - OBJECTIVE: To determine whether faculty triage (FT) activities can shorten
      emergency department (ED) length of stay (LOS). METHODS: This was a comparison
      study measuring the impact of faculty triage vs no faculty triage on ED LOS. It
      was set in an urban county teaching hospital. Subjects were patients presenting
      to the registration desk between 9 AM and 9 PM on 16 consecutive Mondays (August
      2 to November 15, 1999). On eight Mondays, an additional faculty member was
      stationed at the triage desk. He or she was asked to expedite care by rapid
      evaluation orders for diagnostic studies and basic therapeutic interventions, and
      by moving serious patients to the patient care areas. He or she was not provided
      with detailed instructions or protocols. The ED LOS, time of registration
      (TIMEREG), inpatient admission status (ADMIT), x-ray utilization (XRAY), total
      patients registered each day between 9 AM and 9 PM (TOTREG), and patients who
      left without being seen (LWBS) were determined using an ED information system.
      The LOS was analyzed in relation to FT, ADMIT, and XRAY by the Mann-Whitney U
      test. The LOS was related to TIMEREG and TOTREG by simple linear regression.
      Stepwise multiple linear regression models to predict LOS were generated using
      all the variables. RESULTS: Patients without FT (n = 814) had a mean LOS of 445
      minutes. Patients with FT (n = 920) had a mean LOS of 363 minutes. Mean
      difference in LOS was -82 minutes (95% CI = -111 to -53), a reduction of 18%. The
      LOS was also related to: ADMIT +203 minutes (95% CI = 168 to 238), TOTREG -2.7
      min/additional patient registered (95% CI = -1.15 to -4.3), and TIMEREG +0.14
      min/min since 9 AM (95% CI = 0.07 to 0.21). The LWBS was reduced by 46% with FT.
      In multiple regression analysis, ADMIT, FT, TIMEREG, and XRAY were all related to
      LOS, but the model explained only a small part of variance (adjusted R(2) =
      0.093). The faculty cost is estimated to be $11.98/patient. CONCLUSIONS: Faculty
      triage offers a moderate increase in efficiency at this ED, albeit with
      relatively high cost.

PMID- 11581087
TI  - Clinical pearls: Altered mental status in an intravenous drug-abusing patient.

PMID- 11581088
TI  - Clinical pearls: Cold feet.

PMID- 11581089
TI  - Hyperammonemia and coma without hepatic dysfunction induced by valproate therapy.
AB  - The authors report a case of a 41-year-old mentally disabled man with bipolar
      disorder who presented to the emergency department with altered mental status. He
      was found to have a significantly elevated ammonia level (377 microM/L) with no
      signs of hepatic insufficiency. His coma and hyperammonemia were attributed to
      his chronic valproate therapy. This patient had the highest serum ammonia level
      ever reported with a therapeutic valproate level in the absence of any other
      anticonvulsant therapy, metabolic abnormality, or hepatic dysfunction. The
      authors discuss this case and review the current literature on hyperammonemia in
      valproic acid therapy and the use of L-carnitine in these patients.

PMID- 11581090
TI  - Different management options for anaphylactoid purpura with intussusception: a
      case report.
AB  - Intussusception is the most common surgical indication of anaphylactoid purpura.
      About 50% of cases are of the ileo-ileal type. Surgical intervention, rather than
      radiologic reduction, is preferable for older children suffering from
      anaphylactoid purpura with intussusception, where a lead point lesion is often
      found. The authors report a case of anaphylactoid purpura with intussusception
      with spontaneous reduction, and postulate that subsequent to relieving bowel-wall
      edema using antihistamine and steroid therapy, the ileo-ileal intussusception may
      spontaneously reduce.

PMID- 11581091
TI  - Magnetically-guided orotracheal intubation.

PMID- 11581092
TI  - Residential magnetic fields, light-at-night, and nocturnal urinary 6
      sulfatoxymelatonin concentration in women.
AB  - Exposure to 60-Hz magnetic fields may increase breast cancer risk by suppressing
      the normal nocturnal rise in melatonin. This 1994-1996 Washington State study
      investigated whether such exposure was associated with lower nocturnal urinary
      concentration of 6-sulfatoxymelatonin in 203 women aged 20-74 years with no
      history of breast cancer. Each woman was interviewed and provided data on the
      following for a 72-hour period at two different seasons of the year: 1) magnetic
      field and ambient light measured every 30 seconds in her bedroom, 2) personal
      magnetic field measured at 30-second intervals, and 3) complete nighttime urine
      samples on three consecutive nights. Lower nocturnal urinary 6-sulfatoxymelatonin
      level was associated with more hours of daylight, older age, higher body mass
      index, current alcohol consumption, and current use of medications classified as
      beta blockers, calcium channel blockers, or psychotropics. After adjustment for
      these factors, higher bedroom magnetic field level was associated with
      significantly lower urinary concentration of 6-sulfatoxymelatonin during the same
      night, primarily in women who used these medications and during times of the year
      with the fewest hours of darkness. These results suggest that exposure to
      nighttime residential 60-Hz magnetic fields can depress the normal nocturnal rise
      in melatonin.

PMID- 11581093
TI  - Effects of electric and magnetic fields from high-power lines on female urinary
      excretion of 6-sulfatoxymelatonin.
AB  - In 1998, the authors studied the effect of residential exposure to electric and
      magnetic fields from high-power lines on female urinary excretion of 6
      sulfatoxymelatonin (6-OHMS) in the Quebec city, Canada, metropolitan area. A
      sample of 221 women living near a 735-kV line was compared with 195 women the
      same age living away from any power lines. Participants provided morning urine
      samples on 2 consecutive days and wore a magnetic dosimeter for 36 consecutive
      hours to measure personal magnetic exposure. The indoor electric field was
      assessed by spot measurements. After adjustment for other factors associated with
      low melatonin secretion, such as medication use or light exposure, nighttime
      concentration of 6-OHMS was similar in the two groups. When either 24-hour or
      sleep-time exposure to magnetic field or electric field measurements was used, no
      exposure-effect relation was evident. However, the trend of decreasing 6-OHMS
      concentration with age was more pronounced for women living near the lines, as
      was a lower 6-OHMS concentration in women with high body mass index. Chronic
      residential exposure to magnetic fields from high-power lines may accentuate the
      decrease in melatonin secretion observed in some vulnerable subgroups of the
      population.

PMID- 11581094
TI  - Potential risk factors for undifferentiated connective tissue disease among
      women: implanted medical devices.
AB  - A case-control study was conducted among 205 women in Michigan and Ohio who were
      diagnosed with undifferentiated connective tissue disease (UCTD) to investigate
      the significance of self-reported past exposures to implanted silicone-containing
      or non-silicone-containing medical devices. The 205 UCTD cases were compared with
      2,095 controls who were sampled by random digit dialing. When silicone-containing
      devices, including shunts and catheters, were analyzed collectively, a
      significant association was observed (odds ratio (OR) = 2.81, 95% confidence
      interval (CI): 1.34, 5.89). The odds ratio for exposure to breast implants was
      increased, but not significantly (OR = 2.22, 95% CI: 0.65, 7.57). Among the non
      silicone-containing devices, artificial joints (OR = 5.01, 95% CI: 1.60, 15.71)
      and orthopedic metallic fixation devices (OR = 1.95, 95% CI: 1.05, 3.60) were
      associated with UCTD. The estimations of risk associated with implanted medical
      devices in UCTD cases were explored in a comparison with 660 scleroderma patients
      who were ascertained concurrently in Michigan and Ohio. In general, the
      associations that were observed with non-silicone-containing devices, and more
      specifically with the fixation devices, persisted in the comparison of UCTD cases
      with scleroderma patients. The studies conducted among populations in Michigan
      and Ohio are intended to stimulate new hypotheses, innovative approaches, and the
      fostering of understanding of the environmental determinants of autoimmune
      disease.

PMID- 11581095
TI  - Relation of childhood height and later risk of breast cancer.
AB  - The authors sought to examine the hypothesis that girls who were relatively tall
      during the prepubescent period (indicative of an affluent diet and good general
      health) were at increased risk of subsequent breast cancer. They conducted a case
      control study of 214 long-term members who were diagnosed with breast cancer
      during 1973-1995 and who were age 12 years or younger when they first joined
      Kaiser Permanente and of 214 appropriately matched controls. Information was
      obtained from the medical records. While the authors observed the expected
      association of adult height with risk of breast cancer (height at age 15-18
      years, tall-for-age vs. short-for-age: odds ratio = 2.2, 95% confidence interval:
      1.1, 4.3), the association was no stronger earlier in life (height at age 9-11
      years: odds ratio = 1.0, 95% confidence interval: 0.5, 1.8). The study does not
      support a relation between pubertal skeletal growth and adult risk of breast
      cancer. However, it is limited by the inclusion of few postmenopausal women.

PMID- 11581096
TI  - Low-to-moderate alcohol consumption and breast cancer risk by age 50 years among
      women in Germany.
AB  - Studies of the association between alcohol drinking and breast cancer show a
      tendency towards an increase in risk for high consumption levels but yield less
      consistent results for low-to-moderate levels, particularly among premenopausal
      women. In a population-based case-control study in Germany, the authors
      determined the effect of alcohol consumption at low-to-moderate levels on breast
      cancer risk among women up to age 50 years. The study included 706 case women
      whose breast cancer had been newly diagnosed in 1992-1995 and 1,381 residence-
      and age-matched controls. In multivariate conditional logistic regression
      analysis, the adjusted odds ratios for breast cancer were 0.71 (95% confidence
      interval (CI): 0.54, 0.91) for average ethanol intake of 1-5 g/day, 0.67 (95% CI:
      0.50, 0.91) for intake of 6-11 g/day, 0.73 (95% CI: 0.51, 1.05) for 12-18 g/day,
      1.10 (95% CI: 0.73, 1.65) for 19-30 g/day, and 1.94 (95% CI: 1.18, 3.20) for > or
      = 31 g/day. The association with high daily ethanol intake of > or = 19 g was
      modified by educational level, such that odds ratios were 3.7, 1.6, and 0.7 for
      women with low, moderate, and high levels of education, respectively. These data
      suggest that low-level consumption of alcohol does not increase breast cancer
      risk in premenopausal women.

PMID- 11581097
TI  - Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a
      multiethnic cohort.
AB  - Research on the relation between diabetes mellitus and dementia has produced
      conflicting results, and the relation has not been investigated among Blacks and
      Hispanics. In this study, Cox proportional hazards models were used to analyze
      longitudinal data from 1,262 elderly subjects without dementia at baseline (1991
      1996) who were followed for an average of 4.3 years between 1992 and 1997.
      Outcomes were incident Alzheimer's disease and dementia associated with stroke.
      The prevalence of diabetes was 20% at baseline. The adjusted relative risk of
      Alzheimer's disease among persons with diabetes as compared with those without
      diabetes was 1.3 (95% confidence interval (CI): 0.8, 1.9). The adjusted relative
      risk for the composite outcome of Alzheimer's disease and cognitive impairment
      without dementia (without stroke) in subjects with diabetes was 1.6 (95% CI: 1.2,
      2.1). The adjusted relative risk of stroke-associated dementia in persons with
      diabetes was 3.4 (95% CI: 1.7, 6.9). Among Blacks and Hispanics, approximately
      one third of the risk of stroke-associated dementia was attributable to diabetes
      (33% (95% CI: 31, 36) and 36% (95% CI: 33, 37), respectively), as compared with
      17% (95% CI: 13, 22) among Whites. The finding of an association between diabetes
      and the composite outcome of Alzheimer's disease and cognitive impairment without
      dementia (without stroke) is consistent with prior reports of a modest relation
      between diabetes and Alzheimer's disease.

PMID- 11581098
TI  - Mortality with dementia: results from a French prospective community-based
      cohort.
AB  - Despite the magnitude of the problem, little is known about the duration of
      dementia. Survival and risk factors of mortality with dementia and the impact of
      dementia on the risk of death were investigated using the Personnes Agees Quid
      (PAQUID) prospective population-based cohort study between 1988 and 1998.
      Statistical models dealing with interval censoring were performed. Among 3,675
      participants aged 65 years or older and initially nondemented, 2,923 have been
      followed up for 8 years. Of these, 281 persons with incident dementia were
      actively diagnosed. The mean age of onset of dementia was 82.3 years. In the
      total population, the relative risk of dying after developing dementia was
      estimated to be 1.82 (95% confidence interval (CI): 1.77, 2.68) when adjusted for
      sociodemographic variables and comorbidity. Deaths from cerebrovascular diseases
      and respiratory diseases were particularly increased among persons with dementia,
      compared with those without. The median survival time of the persons with
      dementia was estimated to be 4.5 years. Women with dementia had a longer survival
      than did men with dementia, particularly for Alzheimer-type dementia (relative
      risk = 0.47, 95% CI: 0.27, 0.83). Educational level was not significantly
      associated with survival in persons with dementia. These results provide further
      evidence of the malignancy of dementia, which will be a challenge for the 21st
      century.

PMID- 11581099
TI  - Multiple informants: mortality associated with psychiatric disorders in the
      Stirling County Study.
AB  - This paper applies new statistical procedures for analyzing multiple-source
      information about the relation of psychiatric diagnoses to mortality. The data
      come from the Stirling County Study, a longitudinal community investigation of
      adults, that collected multiple-source reports (self-report and physician-report)
      about psychiatric disorders. These reports are used as predictors of mortality
      risk over a 16-year follow-up period (1952-1968). Despite extensive efforts, one
      or both of these reports were sometimes missing. Missingness of self-report was
      related to demographic characteristics as well as to physician-reports of
      psychiatric diagnosis. The statistical procedures used here draw together into a
      single frame of reference both informant reports for the initial Stirling survey
      and relate these to mortality risk using weighted generalized estimating equation
      regression models for time to event data. This unified method has two advantages
      over traditional approaches: 1) the relative predictiveness of each informant can
      be assessed and 2) all subjects contribute to the analysis. The methods are
      applicable to other areas of epidemiology where multiple informant reports are
      used. The results for self-reports and physician-reports of disorders were
      comparable: Psychiatric diagnosis was associated with higher mortality,
      particularly among younger subjects.

PMID- 11581100
TI  - Rates of preterm delivery among Black women and White women in the United States
      over two decades: an age-period-cohort analysis.
AB  - The authors assessed the influence of age, period, and cohort effects on rates of
      preterm delivery in the United States. Rates of preterm delivery for singleton
      births (<37 weeks) in seven age groups (15-19, 20-24,., 45-49 years), five
      periods (1975, 1980, 1985, 1990, 1995), and 11 maternal birth cohorts (1926-1930,
      1931-1935,., 1976-1980) were examined. Over the 20-year study interval, preterm
      delivery increased by 3.6% among Blacks (from 15.5% in 1975 to 16.0% in 1995) and
      by 22.3% among Whites (from 6.9% to 8.4%). Among Black primigravid women, rates
      of preterm delivery increased from 1975 to 1990 and began to decline thereafter;
      among Whites, the rates increased between 1975 and 1995. In Blacks, women aged 25
      29 years had the lowest rates for the first and second births, and women aged 30
      34 years had the lowest rate for subsequent births. In Whites, the age groups
      with the lowest preterm delivery rates were 20-24 years for first births and 25
      29 years for subsequent births. Cohort-specific rates of preterm delivery
      remained fairly constant across age strata and periods for Whites, but a small
      trend was apparent for Blacks aged 30-44 years. The consistency of the observed
      age effects across periods and cohorts suggests that the age effect is partly due
      to biologic factors. The presence of period effects might be linked to the
      increased survival of premature infants or to increased viability among births
      occurring at lower lengths of gestation.

PMID- 11581101
TI  - Sensor, a population-based cohort study on gastroenteritis in the Netherlands:
      incidence and etiology.
AB  - A prospective population-based cohort study with a nested case-control study was
      conducted to estimate the incidence of gastroenteritis and the associated
      pathogens in the general Dutch population. Follow-up of two consecutive cohorts
      was performed by weekly reporting cards from December 1998 to December 1999.
      Cases and controls in the case-control study supplied a questionnaire and stool
      samples. The standardized gastroenteritis incidence was 283 per 1,000 person
      years. The incidence rose with increasing level of education and was higher for
      persons with a history of diarrhea and for young children. Bacterial pathogens
      accounted for 5% of cases, bacterial toxins for 9%, parasites for 6%, and viral
      pathogens for 21%, with Norwalk-like virus (NLV) as the leading pathogen in 11%
      of cases. The gastroenteritis incidence was higher than that reported for
      England, but lower than for the United States. In community cases, viral
      pathogens are the leading cause of gastroenteritis, with NLV being the number one
      cause of illness in all age groups but one. In many countries, preventive
      measures are implemented to decrease bacterial infections. However, additional
      prevention of viral infections, especially NLV, might significantly decrease the
      number of gastroenteritis cases in the community.

PMID- 11581102
TI  - Methods to assess population effectiveness of therapies in human immunodeficiency
      virus incident and prevalent cohorts.
AB  - Two methods are presented for measuring population effectiveness (i.e., reduction
      of disease in a population in which only some receive treatment) of
      antiretroviral therapy among human immunodeficiency virus (HIV)-infected men at
      risk for acquired immunodeficiency syndrome (AIDS) and followed between January
      1, 1986, and June 30, 1999, in the Multicenter AIDS Cohort Study. Method I,
      requiring use of a seroincident cohort, estimates relative hazards of AIDS for
      persons at equal duration of infection. Method II, allowing use of a
      seroprevalent cohort, estimates relative hazards since the beginning of therapy
      eras for persons starting at equal levels of prognostic markers of disease stage
      (CD4 cell count and HIV type 1 RNA). The follow-up interval was divided into four
      calendar periods to characterize different eras of antiretroviral therapy. For
      method I, the relative hazards were 1.52 (95% confidence interval (CI): 0.93,
      2.49), 0.91 (95% CI: 0.66, 1.26), and 0.30 (95% CI: 0.18, 0.51) for the eras of
      no therapy, dual nucleoside therapy, and potent combination antiretroviral
      therapy, respectively (monotherapy was the reference era). For method II, the
      corresponding relative hazards were 1.52 (95% CI: 1.10, 2.09), 1.03 (95% CI:
      0.77, 1.38), and 0.31 (95% CI: 0.21, 0.45). These results extend the measurement
      of population effectiveness from incident to prevalent cohorts and demonstrate
      the ability of cohort studies to complement information provided by clinical
      trials.

PMID- 11581103
TI  - Re: "Changes in body mass index prior to baseline among participants who are ill
      or who die during the early years of follow-up".

PMID- 11581104
TI  - Re: "Immunity to poliomyelitis in the Netherlands".

PMID- 11581105
TI  - General psychiatrists discovering new roles for a new era... and removing work
      stress.

PMID- 11581106
TI  - Are randomised controlled trials the only gold that glitters?

PMID- 11581107
TI  - Immunology of delirium: new opportunities for treatment and research.

PMID- 11581108
TI  - Systematic meta-review of depot antipsychotic drugs for people with
      schizophrenia.
AB  - BACKGROUND: Long-acting depot antipsychotic medication is a widely used treatment
      for schizophrenia. AIMS: To synthesise relevant systematic Cochrane reviews.
      METHOD: The Cochrane Database was searched and summary data were extracted from
      randomised controlled clinical trials of depots. RESULTS: Standard dose depot v.
      placebo resulted in significantly less relapse but more movement disorders. Those
      on depots (v. oral drugs) showed more global change on one outcome measure;
      relapse and adverse effects showed no difference. Comparisons showed no
      convincing advantages for one depot over another. CONCLUSIONS: Depot
      antipsychotics are safe and effective. They may confer a small benefit over oral
      drugs on global outcome. Those for whom depots are most indicated may not be
      represented. Large studies are required to discern differences in relapse rates
      and long-term adverse effects, and data on satisfaction, quality of life and
      economics.

PMID- 11581109
TI  - Systematic review of patient and nurse attitudes to depot antipsychotic
      medication.
AB  - BACKGROUND: Depot antipsychotic medication is used widely in the treatment and
      prophylaxis of severe mental illness. AIMS: To review the literature on patient
      and nurse satisfaction with, and attitudes towards, depots. METHOD: A systematic
      search of Medline, Embase, PsycINFO, CINAHL and The Cochrane Library was
      undertaken, along with citation searches. Studies were selected if
      satisfaction/attitude data were described in the title or abstract and original
      data were included. Study quality was rated. RESULTS: The search produced 1374
      articles; 22 articles met the inclusion criteria, 18 of which were cross
      sectional surveys. Of the 12 studies with relevant data, 10 conveyed a positive
      opinion of depot medication. Five out of six studies comparing depot with oral
      medication showed patient preference for depot. CONCLUSIONS: High-quality data
      examining patient and nurse attitudes regarding depot antipsychotics are sparse.
      What data there are show a positive attitude to depots from patients. Future
      randomised controlled trials should include satisfaction as an outcome.

PMID- 11581110
TI  - Depressive disorders in Europe: prevalence figures from the ODIN study.
AB  - BACKGROUND: This is the first report on the epidemiology of depressive disorders
      from the European Outcome of Depression International Network (ODIN) study. AIMS:
      To assess the prevalence of depressive disorders in randomly selected samples of
      the general population in five European countries. METHOD: The study was designed
      as a cross-sectional two-phase community study using the Beck Depression
      inventory during Phase 1, and the Schedule for Clinical Assessment in
      Neuropsychiatry during Phase 2. RESULTS: An analysis of the combined sample
      (n=8.764) gave an overall prevalence of depressive disorders of 8.56% (95% CI
      7.05-10.37). The figures were 10.05% (95% CI 7.80-12.85) for women and 6.61% (95%
      CI 4.92-8.83) for men. The centres fall into three categories: high prevalence
      (urban Ireland and urban UK), low prevalence (urban Spain) and medium prevalence
      (the remaining sites). CONCLUSIONS: Depressive disorder is a highly prevalent
      condition in Europe. The major finding is the wide difference in the prevalence
      of depressive disorders found across the study sites.

PMID- 11581111
TI  - Dimensional perspective on the recognition of depressive symptoms in primary
      care: The Hampshire Depression Project 3.
AB  - BACKGROUND: Most studies of the recognition of depression in primary care have
      used a categorical definition of depression. This may overstate the extent of the
      problem. AIMS: Our objective was to investigate the relationship between severity
      and recognition of depression, and its modification by patient and practitioner
      characteristics. METHOD: An association study in multiple consecutive adult
      cohorts of 18 414 primary care consultations drawn from a representative sample
      of 156 general practitioners in Hampshire, UK. RESULTS: There was a curvilinear
      relationship between the severity of depression and practitioners' ratings of
      depression. One case of probable depression was missed in every 28.6
      consultations. Anxiety and unemployment altered the chances of recognition, but
      age, gender and deprivation scores did not. CONCLUSIONS: A dimensional approach
      to severity of depression shows that general practitioners may be better able to
      recognise depression than previous categorical studies have suggested. Efforts to
      improve the care of depression should therefore focus on doctors who have been
      shown to have difficulty making the diagnosis and on improving the treatment of
      identified patients.

PMID- 11581112
TI  - Prevalence of obsessive-compulsive disorder in the British nationwide survey of
      child mental health.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a disorder that appears to be
      underdiagnosed and undertreated, despite the evidence for effective treatments.
      There are variable estimates of OCD prevalence in the under-16s and published
      rates give little indication of age trends. AIMS: To establish the prevalence and
      associates of OCD in young people aged 5-15 years. METHOD: A nationwide (UK)
      epidemiological study of rates of psychiatric disorder in 5- to 15-year-olds
      (1999 British Child Mental Health Survey): 10 438 children were assessed.
      RESULTS: Twenty-five children with OCD were identified (weighted overall
      prevalence 0.25%; 95% CI 0.14-0.35), with prevalence rising exponentially with
      increasing age. Compared with normal controls, children with OCD were more likely
      to be from lower socio-economic class and of lower intelligence. Only three of
      these children had been seen by specialist children's services. CONCLUSIONS:
      Although OCD is rare in young children, the rate increases towards the adult
      rates at puberty. Children with OCD have additional psychosocial disadvantage.
      The majority of the childhood cases identified in this survey appear to have been
      undetected and untreated.

PMID- 11581113
TI  - Grey matter abnormalities in obsessive-compulsive disorder: statistical
      parametric mapping of segmented magnetic resonance images.
AB  - BACKGROUND: Although a number of functional imaging studies are in agreement in
      suggesting orbitofrontal and subcortical hyperfunction in the pathophysiology of
      obsessive-compulsive disorder (OCD), the structural findings have been
      contradictory. AIMS: To investigate grey matter abnormalities in patients with
      OCD by employing a novel voxel-based analysis of magnetic resonance images.
      METHOD: Statistical parametric mapping was utilised to compare segmented grey
      matter images from 25 patients with OCD with those from 25 matched controls.
      RESULTS: Increased regional grey matter density was found in multiple cortical
      areas, including the left orbitofrontal cortex, and in subcortical areas,
      including the thalamus. On the other hand, regions of reduction were confined to
      posterior parts of the brain, such as the left cuneus and the left cerebellum.
      CONCLUSIONS: Increased grey matter density of frontal-subcortical circuits,
      consonant with the hypermetabolic findings from functional imaging studies, seems
      to exist in patients with OCD, and cerebellar dysfunction may be involved in the
      pathophysiology of OCD.

PMID- 11581114
TI  - Comparison of the incidence of schizophrenia in rural Dumfries and Galloway and
      urban Camberwell.
AB  - BACKGROUND: Being born or living in urban areas is associated with high rates of
      schizophrenia. However, few studies have compared the incidence in urban/rural
      areas using the same methodology. AIMS: To compare service-based incidence rates
      for schizophrenia in rural Dumfries and Galloway in south-west Scotland with
      urban Camberwell in south-east London. METHOD: Using Research Diagnostic Criteria
      diagnoses from the OPCRIT computer algorithm, we compared the incidence of
      schizophrenia over 12 years (1979-1984 and 1992-1997) using indirect
      standardisation techniques and Poisson regression modelling. RESULTS: The
      incidence was 61% higher in urban Camberwell than in rural Dumfries and Galloway
      (standardised incidence ratio (SIR)=1.61; 95% CI=1.42-1.81). There was no
      difference in incidence when we compared the White population in Camberwell with
      Dumfries and Galloway (SIR=1.12; 95% CI=0.86-1.43). CONCLUSIONS: The incidence of
      schizophrenia in urban Camberwell was higher than that in rural Dumfries and
      Galloway; the high incidence of non-Whites in Camberwell largely explains the
      urban/rural difference.

PMID- 11581115
TI  - Duration of untreated psychosis and cognitive functioning in first-episode
      patients.
AB  - BACKGROUND: The "toxicity" model of duration of untreated psychosis (DUP)
      suggests that longer DUP will be associated with poorer performance on cognitive
      tests in first-episode patients. AIMS: To test this hypothesis on a sample of 113
      patients in a community-based early intervention programme for psychosis. METHOD:
      Information was collected concerning a number of possible predictors of cognitive
      functioning including DUP. These were examined for their relation to performance
      on an extensive battery of cognitive tests administered shortly after the
      patients' admission to the programme. RESULTS: Although several variables such as
      gender, premorbid adjustment, education and handedness predicted cognitive
      functioning, no relation was found between DUP and performance on any component
      of the test battery. CONCLUSIONS: Findings do not provide support for a toxic
      effect of DUP on cognitive functioning. Other mechanisms through which DUP might
      affect outcome such as psychological engulfment, social support and adherence to
      medication are discussed.

PMID- 11581116
TI  - Association between schizophrenia and social inequality at birth: case-control
      study.
AB  - BACKGROUND: The association between social inequality at birth and subsequent
      risk of schizophrenia is uncertain. AIMS: To investigate the relationship between
      adult-onset schizophrenia and two indicators of social inequality at birth:
      social class and area of residence. METHOD: A matched case-control design was
      used with data from birth certificates of first-episode cases and age- and gender
      matched controls. RESULTS: Risk increased with increasing levels of deprivation
      at birth. Subjects whose fathers were social class IV-V or who were born in
      deprived areas were at increased risk of schizophrenia (odds ratio=2.1; 95%
      Cl=0.8-5.5). Risk was greater in those with both of these indicators (odds
      ratio=8.1; 95% Cl=2.7-23.9). There was some evidence that associations were
      stronger in older subjects. Exclusion of African-Caribbeans or cases with
      positive family history somewhat attenuated the association. CONCLUSIONS:
      Indicators of social inequality at birth are associated with increased risk of
      adult-onset schizophrenia, suggesting that environmental factors are important
      determinants of schizophrenic disorders.

PMID- 11581117
TI  - Aggressive behaviour in patients with schizophrenia is associated with catechol-O
      methyltransferase genotype.
AB  - BACKGROUND: Evidence exists for an association between aggression and
      schizophrenia. Although the aetiology of aggression is multifactorial, three
      studies have reported associations between polymorphisms of the catechol-O
      methyltransferase (COMT) gene and aggression in schizophrenia. AIMS: To replicate
      these findings in a larger sample using the Overt Aggression Scale (OAS). METHOD:
      A sample of 180 people with DSM-IV schizophrenia were rated for aggression using
      the OAS. Kruskal-Wallis and contingency table analyses were applied to the OAS
      results. RESULTS: The high-activity homozygotes showed significantly higher
      scores of aggression, whereas the heterozygotes showed significantly lower
      scores. The odds ratio for aggression for the high-activity homozygotes was 2.07
      (95% Cl=1.03-4.15), whereas that for the heterozygotes was 0.54 (95% Cl=0.30
      1.00). CONCLUSIONS; The high-activity COMT homozygote confers a higher risk of
      recorded aggression in schizophrenia. Heterozygotes had a significantly lower
      risk, which may represent an example of heterosis/heterozygote advantage.

PMID- 11581118
TI  - Antidopaminergic effects of dietary tyrosine depletion in healthy subjects and
      patients with manic illness.
AB  - BACKGROUND: In rats, amino acid mixtures lacking tyrosine and its precursor
      phenylalanine decrease the release of dopamine produced by the psychostimulant
      drug amphetamine. Amphetamine has been proposed as a model for clinical mania.
      AIMS: To assess whether dietary tyrosine depletion attenuates the psychostimulant
      effects of methamphetamine in healthy volunteers and diminishes the severity of
      mania in acutely ill patients. METHOD: Sixteen healthy volunteers received a
      tyrosine-free amino acid mixture and a control mixture in a double-blind
      crossover design 4 h before methamphetamine (0.15 mg/kg). Twenty in-patients
      meeting DSM-IV criteria for mania were allocated blindly and randomly to receive
      either the tyrosine-free mixture or the control mixture. RESULTS: The tyrosine
      free mixture lowered both subjective and objective measures of the
      psychostimulant effects of methamphetamine. Ratings of mania were lower in the
      patients who received the tyrosine-free mixture. CONCLUSIONS; Decreased tyrosine
      availability to the brain attenuates pathological increases in dopamine
      neurotransmission following methamphetamine administration and putatively in
      mania.

PMID- 11581120
TI  - PTSD and stillbirth.

PMID- 11581119
TI  - Mental health of migrant elders--the Islington study.
AB  - BACKGROUND: In the UK, 6% of those aged 65 years and over were born abroad, most
      of whom now live in inner-city areas. It has been suggested that ethnic elders
      are particularly vulnerable to mental illness. AIMS: To compare the prevalence of
      dementia and depression in older migrants with those born in the UK. METHOD: A
      cross-sectional community study of 1085 people aged 65 years or older in an inner
      London borough. RESULTS: Compared with those born in the UK, the prevalence of
      dementia was raised in African-Caribbeans (17.3%, relative risk=1.72, Cl=1.06
      2.81) and lower for the Irish-born (3.6%, relative risk=0.36, Cl=0.17-0.87). All
      those of African-Caribbean country of birth were significantly younger (P=0.000)
      but no more likely to be taking antihypertensive drugs. They were no more likely
      to report having cardiovascular problems but had increased rates of diabetes
      (P<0.0000). The overall prevalence of depression was 18.3% (95% Cl=16.1-20.7).
      The highest prevalence rate was found among those born in Greece and Turkey
      (27.2%, Cl=17.9-39.6). Migration per se does not appear to be a risk for
      depression and dementia in this population. CONCLUSIONS: The excess of dementia
      may be of vascular aetiology. There is the potential for primary or secondary
      prevention.

PMID- 11581121
TI  - NICE guidelines and the treatment of Alzheimer's disease: evidence-based medicine
      may be discriminatory.

PMID- 11581122
TI  - Psychiatric services in developing countries.

PMID- 11581124
TI  - Cannabis regimes--a response.

PMID- 11581125
TI  - Need for paediatric-psychiatric liaison.

PMID- 11581126
TI  - Monthly variation in suicide is still strong in the USA.

PMID- 11581127
TI  - Evolution, biological reductionism and closed minds.

PMID- 11581130
TI  - Regression of left ventricular hypertrophy and improved prognosis: some hope now
      . . . or hype?

PMID- 11581131
TI  - Titin: an elastic link between length and active force production in myocardium.

PMID- 11581132
TI  - Magnetic resonance imaging permits in vivo monitoring of catheter-based vascular
      gene delivery.
AB  - BACKGROUND: Gene therapy is an exciting frontier in modern medicine. To date,
      most investigations about the imaging of gene therapy have primarily focused on
      noncardiovascular systems, and no in vivo imaging modalities are currently
      available for monitoring vascular gene therapy. The purpose of this study was to
      develop an in vivo imaging tool to monitor a catheter-based vascular gene
      delivery procedure. METHODS AND RESULTS: We produced gadolinium/blue dye and
      gadolinium/gene-vector media by mixing Magnevist with a trypan-blue or a
      lentiviral vector carrying a green fluorescent protein (GFP) gene. The gadolinium
      was used as an imaging marker for magnetic resonance (MR) imaging to visualize
      vessel wall enhancement, and the blue dye/GFP was used as a tissue stain marker
      for histology/immunohistochemistry to confirm the success of the transfer. Using
      Remedy gene delivery catheters, we transferred the gadolinium/blue dye (n=8) or
      gadolinium/GFP lentivirus (n=4) into the arteries of 12 pigs, that were monitored
      under high-resolution MR imaging. The results showed, in all 12 pigs, the
      gadolinium enhancement of the target vessel walls on MR imaging and the blue/GFP
      staining of the target vessel tissues with histology/immunohistochemistry. This
      study shows the potential of using MR imaging to dynamically visualize (1) where
      the gadolinium/genes are delivered; (2) how the target portion is marked; and (3)
      whether the gene transfer procedure causes complications. CONCLUSIONS: We present
      a technical development that uses high-resolution MR imaging as an in vivo
      imaging tool to monitor catheter-based vascular gene delivery.

PMID- 11581133
TI  - Adventitial cells do not contribute to neointimal mass after balloon angioplasty
      of the rat common carotid artery.
AB  - BACKGROUND: Previous studies suggest that the migration of adventitial cells into
      the neointima after balloon angioplasty might have an important role in vascular
      lesion formation. The current experiments were designed to study the migration of
      adventitial cells in response to mechanical injury of the rat carotid artery.
      METHODS AND RESULTS: Adventitial cells were stained in situ with PKH26, a
      fluorescent dye, after balloon angioplasty of the rat common carotid artery.
      Animals were killed at different time points, and tissue sections were examined
      under light and fluorescence microscopy. PKH26-labeled cells were detected
      exclusively in the adventitia. No labeled cells were present in the media or the
      neointima at any time point examined. A highly cellular neoadventitial layer
      composed of myofibroblasts exhibited an extensive proliferative response 3 days
      after injury over the entire adventitial circumference. CONCLUSIONS: Despite the
      prominent role that adventitial myofibroblasts seem to have in the
      postangioplasty remodeling process, they do not migrate to the medial or intimal
      layers in the rat carotid artery angioplasty model.

PMID- 11581134
TI  - Infusion of light chains from patients with cardiac amyloidosis causes diastolic
      dysfunction in isolated mouse hearts.
AB  - BACKGROUND: Primary (AL) amyloidosis is a plasma cell dyscrasia characterized by
      clonal production of immunoglobulin light chains (LC) resulting in the subsequent
      systemic deposition of extracellular amyloid fibrils. Cardiac involvement is
      marked by the hemodynamic pattern of impaired diastolic filling and restrictive
      cardiomyopathy. Although cardiac death in patients with AL amyloidosis is usually
      associated with extensive myocardial infiltration, the infiltration alone does
      not correlated with the degree of heart failure or survival. We hypothesized that
      circulating monoclonal LC may directly impair cardiac function, in addition to
      any mechanical effects of amyloid fibril deposition. Therefore, we examined the
      effects of amyloid LC proteins on diastolic and systolic cardiac function, as
      measured in an isolated mouse heart model. METHODS AND RESULTS: LC were obtained
      from patients with nonamyloid disease or from those with noncardiac, mild
      cardiac, and severe cardiac involved AL amyloidosis. Saline or LC (100
      microgram/mL) was infused into a Langendorff-perfused, isovolumically contracting
      mouse heart. Saline and control, noncardiac, and mild-cardiac LC infusions did
      not alter ex vivo cardiac function. In contrast, infusion of sever cardiac LC
      resulted in marked impairment of ventricular relaxation with preservation of
      contractile function. CONCLUSION: These results demonstrate that infusion of LC
      from patients with AL amyloidosis result in diastolic dysfunction similar to that
      observed in patients with cardiac involved AL amyloidosis, and they suggest that
      amyloid LC proteins may contribute directly to the pathogenesis and the rapid
      progression of amyloid cardiomyopathy, independent of extracellular fibril
      deposition.

PMID- 11581135
TI  - Expression of interleukin-18 in human atherosclerotic plaques and relation to
      plaque instability.
AB  - BACKGROUND: Interleukin (IL)-18 is a potent proinflammatory cytokine with
      potential atherogenic properties. Its expression and role in atherosclerosis,
      however, are unknown. METHODS AND RESULTS: In the present study, we examined
      stable and unstable human carotid atherosclerotic plaques retrieved by
      endarterectomy for the presence of IL-18 using reverse transcription-polymerase
      chain reaction (PCR), Western blot, and immunohistochemical techniques. IL-18 was
      highly expressed in the atherosclerotic plaques compared with control normal
      arteries and was localized mainly in plaque macrophages. IL-18 receptor was also
      upregulated in plaque macrophages and endothelial cells, suggesting potential
      biological effects. To examine the role of IL-18 in atherosclerosis, we
      determined the relation between IL-18 mRNA expression and signs of plaque
      instability using real-time quantitative PCR. Interestingly, significantly higher
      levels of IL-18 mRNA were found in symptomatic (unstable) plaques than
      asymptomatic (stable) plaques (P<0.01). CONCLUSIONS: These results suggest, for
      the first time, a major role for IL-18 in atherosclerotic plaque destabilization
      leading to acute ischemic syndromes.

PMID- 11581136
TI  - Stent placement compared with balloon angioplasty for small coronary arteries: in
      hospital and 6-month clinical and angiographic results.
AB  - BACKGROUND: Stenting has been demonstrated to be superior to balloon angioplasty
      in de novo focal lesions located in large native vessels. However, in small
      vessels, the benefit of stenting remains questionable. METHODS AND RESULTS: A
      total of 381 symptomatic patients with de novo focal lesion located on a small
      coronary segment vessel (<3 mm) were randomly assigned to either stent
      implantation (192 patients; 197 lesions) or standard balloon angioplasty (189
      patients; 198 lesions). The primary end point was the angiographic restenosis
      rate at 6 months, as determined by quantitative coronary angiography. On
      intention-to-treat analysis, angiographic success rate and major adverse cardiac
      events were comparable: 97.9% and 4.6% versus 93.9% and 5.8% in the stent group
      and the balloon group, respectively. After the procedure, a larger acute gain was
      achieved with stent placement (1.35+/-0.45 versus 0.94+/-0.47 mm, P=0.0001),
      resulting in a larger minimal lumen diameter (2.06+/-0.42 versus 1.70+/-0.46 mm,
      P=0.0001). At follow-up (obtained in 91% of patients), angiographic restenosis
      rate was 21% in the stent group versus 47% in the balloon group (P=0.0001), a
      risk reduction of 55%. Repeat target lesion revascularization was less frequent
      in the stent group (13% versus 25%, P=0.0006). CONCLUSIONS: Elective stent
      placement in small coronary arteries with focal de novo lesions is safe and
      associated with a marked reduction in restenosis rate and subsequent target
      lesion revascularization rate at 6 months.

PMID- 11581137
TI  - Long-term clinical outcomes after unprotected left main trunk percutaneous
      revascularization in 279 patients.
AB  - BACKGROUND: Percutaneous coronary revascularization (PCI) has been increasingly
      applied to unprotected left main trunk (LMT) lesions, with varied long-term
      success. This study attempts to define the predictors of outcome in this
      population. METHODS AND RESULTS: Two hundred seventy-nine consecutive patients
      who had LMT PCI at 1 of 25 sites between 1993 and 1998 were studied. Forty-six
      percent of these patients were deemed inoperable or at high surgical risk. Thirty
      eight patients (13.7%) died in hospital, and the rest were followed up for a mean
      of 19 months. The 1-year incidence was 24.2% for all-cause mortality, 20.2% for
      cardiac mortality, 9.8% for myocardial infarction, and 9.4% for CABG. Independent
      correlates of all-cause mortality were left ventricular ejection fraction </=30%,
      mitral regurgitation grade 3 or 4, presentation with myocardial infarction and
      shock, creatinine >/=2.0 mg/dL, and severe lesion calcification. For the 32% of
      patients <65 years old with left ventricular ejection fraction >30% and without
      shock, the prevalence of these adverse risk factors was low. No periprocedural
      deaths were observed in this low-risk subset, and the 1-year mortality was only
      3.4%. CONCLUSIONS: Patients undergoing unprotected LMT PCI have frequent serious
      comorbidities and consequently have high event rates. PCI may be an alternative
      to CABG for a select proportion of elective patients and may also be appropriate
      for highly symptomatic inoperable patients. Meticulous follow-up of hospital
      survivors is required because of the rather high mortality during the first few
      months after treatment.

PMID- 11581138
TI  - Reduction of cardiovascular risk by regression of electrocardiographic markers of
      left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor
      ramipril.
AB  - BACKGROUND: Electrocardiographic markers of left ventricular hypertrophy (LVH)
      predict poor prognosis. We determined whether the ACE inhibitor ramipril prevents
      the development and causes regression of ECG-LVH and whether these changes are
      associated with improved prognosis independent of blood pressure reduction.
      METHODS AND RESULTS: In the Heart Outcomes Prevention Evaluation (HOPE) study,
      patients at high risk were randomly assigned to ramipril or placebo and followed
      for 4.5years. ECGs were recorded at baseline and at study end. We compared
      prevention/regression and development/persistence of ECG-LVH in the two groups
      and related these changes to outcomes. At baseline, 676 patients had LVH (321 in
      the ramipril group and 355 in the placebo group) and 7605 patients did not have
      LVH (3814 in the ramipril group and 3791 in the placebo group). By study end, 336
      patients in the ramipril group (8.1%) compared with 406 in the placebo group
      (9.8%) had development/persistence of LVH; in contrast, 3799 patients in the
      ramipril group (91.9%) compared with 3740 in the placebo group (90.2%) had
      regression/prevention of LVH (P=0.007). The effect of ramipril on LVH was
      independent of blood pressure changes. Patients who had regression/prevention of
      LVH had a lower risk of the predefined primary outcome (cardiovascular death,
      myocardial infarction, or stroke) compared with those who had
      development/persistence of LVH (12.3% versus 15.8%, P=0.006) and of congestive
      heart failure (9.3% versus 15.4%, P<0.0001). CONCLUSIONS: The ACE inhibitor
      ramipril decreases the development and causes regression of ECG-LVH independent
      of blood pressure reduction, and these changes are associated with reduced risk
      of death, myocardial infarction, stroke, and congestive heart failure.

PMID- 11581139
TI  - Effect of clinical risk stratification on cost-effectiveness of the implantable
      cardioverter-defibrillator: the Canadian implantable defibrillator study.
AB  - BACKGROUND: Three randomized clinical trials showed that implantable cardioverter
      defibrillators (ICDs) reduce the risk of death in survivors of ventricular
      tachyarrhythmias, but the cost per year of life gained is high. A substudy of the
      Canadian Implantable Defibrillator Study (CIDS) showed that 3 clinical factors,
      age >/=70 years, left ventricular ejection fraction </=35%, and New York Heart
      Association class III, predicted the risk of death and benefit from the ICD. We
      estimated the extent to which selecting patients for ICD therapy based on these
      risk factors makes ICD therapy more economically attractive. METHODS AND RESULTS:
      Patients in CIDS were grouped according to whether they had >/=2 of 3 risk
      factors. Incremental cost-effectiveness of ICD therapy was computed as the ratio
      of the difference in mean cost to the difference in life expectancy between the 2
      groups. Over 6.3 years, the mean cost per patient in the ICD group was Canadian
      (C) $87 715 versus $38 600 in the amiodarone group (C$1 approximately US$0.67).
      Life expectancy for the ICD group was 4.58 years versus 4.35 years for
      amiodarone, for an incremental cost-effectiveness of ICD therapy of C$213 543 per
      life-year gained. The cost per life-year gained in patients with >/=2 factors was
      C$65 195, compared with C$916 659 with <2 risk factors. CONCLUSIONS: The cost
      effectiveness of ICD therapy varies by patient risk factor status. The use of ICD
      therapy in patients who have >/=2 risk factors of age >/=70 years, left
      ventricular ejection fraction </=35%, and NYHA class III is C$65 195 to gain a
      year of life.

PMID- 11581140
TI  - Central arterial compliance is associated with age- and habitual exercise-related
      differences in cardiovagal baroreflex sensitivity.
AB  - Background- Cardiovagal baroreflex sensitivity (BRS) declines with age but is
      favorably modulated by habitual aerobic exercise. We tested the hypothesis that
      compliance (transducing capacity) of an elastic artery in which baroreceptors are
      located is associated with these age-exercise interactions. Methods and Results-
      Nine young (28+/-1 years old) and 9 older (65+/-1) sedentary and 10 young (27+/
      1) and 9 older (63+/-2) endurance-trained healthy men were studied. Cardiovagal
      BRS was assessed conventionally (R-R interval-systolic blood pressure [SBP]
      relation) by the Oxford technique. Because of age-associated increases in central
      arterial stiffness, cardiovagal BRS was expressed with both peripheral (Finapres)
      and central (applanation tonometry) SBP values. The change in carotid artery end
      systolic lumen diameter (ultrasonography) per unit increase in SBP and the slope
      of the R-R interval-carotid artery diameter relation also were determined.
      Cardiovagal BRS declined with age in both sedentary ( approximately 65%) and
      endurance-trained ( approximately 40%) men but was higher in endurance-trained
      than sedentary older men regardless of the SBP values used (all P<0.05). Changes
      in carotid artery lumen diameter per unit increase in SBP mirrored these
      differences in cardiovagal BRS (all P<0.05). Thus, R-R interval prolongation per
      unit increase in carotid artery diameter was not different among the groups
      (P>0.70). Conclusions- These results demonstrate that age- and habitual exercise
      related differences in cardiovagal BRS are associated with corresponding
      differences in carotid artery compliance among healthy men.

PMID- 11581141
TI  - Birth weight and blood pressure in young adults: a prospective twin study.
AB  - BACKGROUND: The intrauterine environment may be a critical period for the
      development of hypertension in later life. In the present study, we applied the
      twin approach to estimate the contribution of genetic and environmental causes
      that may underlie the birth weight-adult blood pressure association. METHODS AND
      RESULTS: Birth weights of 418 twin pairs were obtained prospectively, and resting
      and 24-hour ambulatory blood pressures were obtained at the age of 18 to 34
      years. In women, resting systolic blood pressure decreased 4.27 mm Hg (P<0.001)
      and diastolic pressure decreased 2.18 mm Hg (P=0.02) per kilogram increase in
      birth weight. Similar associations were found for ambulatory measurements,
      although these were somewhat less pronounced. Pair-wise analysis confirmed these
      findings: twin pairs of whom both members had a low birth weight (<2500 g) had a
      higher systolic blood pressure compared with twins who both had a high birth
      weight (>/=2500 g). Systolic blood pressure of the lightest of a low-birth-weight
      pair was >/=4.7 mm Hg (P=0.02) higher and of the heaviest >/=2.4 mm Hg higher
      (P=0.2) than similar measurements in high-birth-weight pairs. Intrapair
      differences in blood pressure between the lightest and the heaviest at birth were
      only present in low-birth-weight pairs. The results were similar for monozygotic
      and dizygotic twin pairs. In men, no associations were found between birth weight
      and adult blood pressure. CONCLUSIONS: These findings suggest that prenatal
      programming of adult blood pressure occurs at least in female twins. We suggest
      that particularly maternal influences, experienced by both twin members, may
      underlie the association between birth weight and blood pressure. The
      fetoplacental unit seems to influence blood pressure only when both fetuses had
      low birth weight.

PMID- 11581142
TI  - Length dependence of tension generation in rat skinned cardiac muscle: role of
      titin in the Frank-Starling mechanism of the heart.
AB  - BACKGROUND: At the basis of the Frank-Starling mechanism is the intrinsic ability
      of cardiac muscle to produce active tension in response to stretch. Titin, a
      giant filamentous molecule involved in passive tension development, is intimately
      associated with the thick filament in the sarcomere. Titin may therefore
      contribute to active tension development by modulating the thick filament
      structure when the muscle is elongated. METHODS AND RESULTS: Rat skinned right
      ventricular trabeculae were used. Passive tension at a sarcomere length (SL) of
      2.0 to 2.4 micrometer was decreased after treatment of the preparation with
      trypsin (0.25 microgram/mL) for 13 minutes in the relaxed state at 20 degrees C.
      This mild trypsin treatment degraded titin without affecting other major
      contractile proteins. The sarcomere structure was little affected by brief
      contractions in the trypsin-treated preparations. When SL was adjusted to the
      slack SL (1.9 micrometer), active tension was unaffected by trypsin under partial
      (pCa 5.55) and maximal (pCa 4.8) activation. At longer SLs, however, active
      tension was significantly (P<0.01) decreased after trypsin treatment at either
      pCa. The increase in active tension on reduction of interfilament lattice
      spacing, produced by dextran T-500 (molecular weight approximately 500 000), was
      not influenced by trypsin (SL 1.9 micrometer). In trypsin-treated preparations,
      the increase in active tension as a function of muscle diameter was nearly the
      same for lengthening and osmotic compression at the slack SL. CONCLUSIONS: The
      length-dependent activation in cardiac muscle, an underlying mechanism of the
      Frank-Starling law of the heart, is at the myofilament level, predominantly
      modulated by titin and interfilament lattice spacing changes.

PMID- 11581143
TI  - 12/15-Lipoxygenase gene disruption attenuates atherogenesis in LDL receptor
      deficient mice.
AB  - BACKGROUND: Human 15-lipoxygenase (LO) and its murine analogue 12/15-LO are
      capable of directly oxidizing esterified fatty acids in lipoproteins and
      phospholipids. Because these oxidized products possess atherogenic properties, it
      was suggested that LOs may be involved in enhancing atherogenesis. Previous in
      vivo tests of the role of LOs in atherogenesis animal models, however, have
      yielded conflicting results. METHODS AND RESULTS: Aiming to study the role of the
      12/15-LO in murine atherogenesis, we crossed LDL-receptor-deficient mice (LDL-R(
      /-)) with 12/15-LO-knockout mice and evaluated plaque formation 3 to 18 weeks
      after initiation of a high-fat diet. Atherosclerotic lesions were considerably
      reduced in the LDL-R/12/15-LO-double-knockout mice compared with LDL-R(-/-) mice
      at 3, 9, 12, and 18 weeks, at the aortic root as well as throughout the aorta.
      The cellular composition of plaques from mice deficient in 12/15-LO did not
      differ with respect to macrophage and T-lymphocyte content compared with plaques
      from 12/15-LO littermates. CONCLUSIONS: 12/15-LO plays a dominant role in
      promoting atherogenesis in LDL-R(-/-) mice.

PMID- 11581144
TI  - Developing a vasopressor combination in a pig model of adult asphyxial cardiac
      arrest.
AB  - BACKGROUND: The purpose of this study was to investigate the effects of
      vasopressin versus epinephrine, and both drugs combined, in a porcine model of
      simulated adult asphyxial cardiac arrest. METHODS AND RESULTS: At approximately 7
      minutes after the endotracheal tube had been clamped, cardiac arrest was present
      in 24 pigs and remained untreated for another 8 minutes. After 4 minutes of basic
      life support cardiopulmonary resuscitation, pigs were randomly assigned to
      receive, every 5 minutes, either epinephrine (45, 200, or 200 microgram/kg; n=6);
      vasopressin (0.4, 0.8, or 0.8 U/kg; n=6); or epinephrine combined with
      vasopressin (high-dose epinephrine/vasopressin combination, microgram/kg and
      U/kg: 45/0.4, 200/0.8, or 200/0.8; n=6; optimal-dose epinephrine/vasopressin
      combination, 45/0.4, 45/0.8, or 45/0.8; n=6). Mean+/-SEM coronary perfusion
      pressure was significantly (P<0.05) higher 90 seconds after high- or optimal-dose
      epinephrine/vasopressin combinations versus vasopressin alone and versus
      epinephrine alone (37+/-10 versus 25+/-7 versus 19+/-8 versus 6+/-3 mm Hg; 42+/-6
      versus 40+/-5 versus 21+/-5 versus 14+/-6 mm Hg; and 39+/-6 versus 37+/-4 versus
      9+/-3 versus 12+/-4 mm Hg, respectively). Six of 6 high-dose, 6 of 6 optimal-dose
      vasopressin/epinephrine combination, 0 of 6 vasopressin, and 1 of 6 epinephrine
      pigs had return of spontaneous circulation (P<0.05). CONCLUSIONS: Epinephrine
      combined with vasopressin, but not epinephrine or vasopressin alone, maintained
      elevated coronary perfusion pressure during cardiopulmonary resuscitation and
      resulted in significantly higher survival rates in this adult porcine asphyxial
      model.

PMID- 11581145
TI  - Electrical remodeling in pressure-overload cardiac hypertrophy: role of
      calcineurin.
AB  - BACKGROUND: Myocyte hypertrophy accompanies many forms of heart disease, but its
      contribution to electrical remodeling is unknown. METHODS AND RESULTS: We studied
      mouse hearts subjected to pressure overload by surgical thoracic aortic banding.
      In unbanded control hearts, action potential duration (APD) was significantly
      longer in subendocardial myocytes compared with subepicardial myocytes.
      Hypertrophy-associated APD prolongation was significantly greater in
      subendocardial myocytes compared with subepicardial myocytes, indicating stress
      induced amplification of repolarization dispersion. To investigate the underlying
      basis, we performed voltage-clamp recordings on dissociated myocytes. Under
      control unoperated conditions, subendocardial myocytes exhibited significantly
      less transient outward current (I(to)) than did subepicardial cells. Hypertrophy
      was not associated with significant changes in I(to), sustained current, or
      inward rectifier current densities, but peak L-type Ca(2+) current density
      (I(Ca,L)) increased 26% (P<0.05). Recovery from I(Ca,L) inactivation was
      accelerated in hypertrophied myocytes. Inhibition of calcineurin with cyclosporin
      A prevented increases in heart mass and myocyte size but was associated with an
      intermediate APD. The hypertrophy-associated increase in I(Ca,L) and the
      accelerated recovery from inactivation were blocked by cyclosporin A.
      CONCLUSIONS: These data reveal regional variation in the electrophysiological
      response within the left ventricle by way of a mechanism involving upregulated
      Ca(2+) current and calcineurin. Furthermore, these results reveal partial
      uncoupling of electrophysiological and structural remodeling in hypertrophy.

PMID- 11581146
TI  - Increased adenosine monophosphate-activated protein kinase activity in rat hearts
      with pressure-overload hypertrophy.
AB  - BACKGROUND: Recent reports suggest that activation of adenosine monophosphate
      (AMP)-activated protein kinase (AMPK), in response to acute changes in cellular
      energy status in cardiac and skeletal muscles, results in altered substrate
      utilization. We hypothesized that chronic alterations in myocardial energetics in
      hypertrophied hearts (left ventricular hypertrophy, LVH) will lead to elevated
      AMPK activity, which in turn regulates substrate utilization. METHODS AND
      RESULTS: Using (31)P NMR spectroscopy and biochemical assays, we found that in
      LVH hearts, adenosine triphosphate (ATP) concentration decreased by 10%,
      phosphocreatine concentration decreased by 30%, and total creatine concentration
      was unchanged. Thus, the ratio of phosphocreatine/creatine decreased to one third
      of controls, and the ratio of AMP/ATP increased to 5 times above controls. These
      changes were associated with increased alpha(1) and alpha(2) AMPK activity (3.5-
      and 4.8-fold above controls, respectively). The increase in AMPK alpha(1)
      activity was accompanied by a 2-fold increase in alpha(1) expression, whereas
      alpha(2) expression was decreased by 30% in LVH. The basal rate of 2-deoxyglucose
      uptake increased by 3-fold in LVH, which was associated with an increased amount
      of glucose transporters present on the plasma membrane. CONCLUSIONS: These
      results demonstrate for the first time that chronic changes in myocardial
      energetics in hypertrophied hearts are accompanied by significant elevations in
      AMPK activity and isoform-specific alterations in AMPK expression. It also raises
      the possibility that AMPK signaling plays an important role in regulating
      substrate utilization in hypertrophied hearts.

PMID- 11581147
TI  - Peroxisome proliferator-activated receptor gamma activators inhibit cardiac
      hypertrophy in cardiac myocytes.
AB  - BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are transcription
      factors belonging to the nuclear receptor superfamily. PPARgamma mRNA is present
      in cardiac myocytes; however, whether PPARgamma affects cardiac hypertrophy
      remains unknown. METHODS AND RESULTS: We investigated the effects of PPARgamma
      activators on cardiac hypertrophy in neonatal rat cardiac myocytes. Cyclic 4%
      biaxial mechanical strain caused enlargement of cardiac myocytes (1.3-fold versus
      control, P<0.0001), but the PPARgamma activators troglitazone and 15-deoxy
      Delta(12-14)-prostaglandin J(2) (15d-PGJ(2)) (10 micromol/L) inhibited this
      effect (troglitazone, -72%, P<0.0005; 15d-PGJ(2), -88%, P<0.0002). Total cell
      protein was increased by mechanical strain (control, 164.3 microgram/dish;
      strain, 265.5, P<0.0002), and this effect was inhibited by troglitazone and 15d
      PGJ(2) (troglitazone, -61%, P<0.005; 15d-PGJ(2), -72%, P<0.001). [(3)H]Leucine
      uptake was also increased by mechanical strain (1.9-fold versus control,
      P<0.002), and this increase was inhibited by troglitazone and 15d-PGJ(2)
      (troglitazone, -52% at 10 micromol/L, P<0.01; 15d-PGJ(2), -70% at 10 micromol/L,
      P<0.005). An increase in [(3)H]leucine uptake induced by angiotensin II or
      phenylephrine was significantly inhibited by troglitazone and 15d-PGJ(2).
      Mechanical strain induced mRNA expression for brain natriuretic peptide, but
      PPARgamma activators inhibited this induction. Furthermore, PPARgamma activators
      inhibited mechanically induced activation of nuclear factor (NF)-kappaB.
      Pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB activation, inhibited
      strain-induced [(3)H]leucine uptake (-50% at 100 micromol/L, P<0.05).
      CONCLUSIONS: These results demonstrate that PPARgamma activators inhibit cardiac
      hypertrophy in cardiac myocytes and suggest that PPARgamma activators may
      regulate cardiomyocyte hypertrophy at least partially through the NF-kappaB
      pathway.

PMID- 11581148
TI  - Reduced functional expression and molecular synthesis of inducible nitric oxide
      synthase in rostral ventrolateral medulla of spontaneously hypertensive rats.
AB  - BACKGROUND: We demonstrated recently that the prevalence of neuronal (nNOS) over
      inducible (iNOS) nitric oxide synthase activity at the rostral ventrolateral
      medulla (RVLM), the medullary origin of sympathetic neurogenic vasomotor tone,
      and the associated dominance of sympathoexcitation over sympathoinhibition
      underlie the maintenance of sympathetic vasomotor outflow by the endogenous NO.
      Here, we evaluated the hypothesis that a significant downregulation of iNOS at
      the RVLM may play a crucial role in the genesis of augmented sympathetic
      vasomotor tone during hypertension. METHODS AND RESULTS: Spontaneously
      hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats anesthetized
      with propofol were used. Compared with SHR, the hypotension, bradycardia, or
      depression in sympathetic vasomotor tone induced by bilateral microinjection of
      lipopolysaccharide (5 or 10 ng) into the RVLM of WKY rats exhibited significantly
      shorter-onset latency, appreciably steeper slope, and a greater incidence of
      mortality. All these effects of lipopolysaccharide (10 ng) were significantly
      blunted by coadministration of the selective iNOS inhibitor S-methylisothiourea
      (250 pmol). Reverse transcription-polymerase chain reaction and Western blot
      analyses further revealed significantly lower iNOS mRNA and protein levels at the
      ventrolateral medulla in SHR under basal conditions or on activation by
      lipopolysaccharide (10 ng). Conversely, nNOS mRNA and protein levels remained
      constant in the RVLM and were comparable in both strains of rats. CONCLUSIONS: We
      conclude that a significant downregulation in both functional expression and
      molecular synthesis of iNOS at the RVLM may underlie the augmented sympathetic
      vasomotor tone during hypertension.

PMID- 11581149
TI  - Unstable coronary plaque and its relation to coronary calcium.
AB  - Coronary calcium is intimately associated with coronary atherosclerotic plaque
      development. The use of electron-beam computed tomography (EBCT) for accurate
      quantitative measurements has led to an increased interest in understanding the
      clinical importance of coronary calcium, particularly in terms of the ability to
      identify unstable coronary plaques that underlie the clinical acute coronary
      syndromes. Histopathologic studies have demonstrated that calcium is a frequent
      feature of ruptured plaques, but the presence or absence of calcium does not
      allow for reliable distinction between unstable versus stable plaques. This issue
      is complicated by the lack of a prospective definition for "unstable." Plaque
      rupture is sometimes found in apparently healthy subjects and in patients with
      clinically stable disease. Coronary atherosclerosis is a coronary systemic
      disease process. Imaging of coronary calcium, although unable to identify a
      localized unstable plaque, potentially can identify the more clinically pertinent
      "unstable patient." Almost all patients with a recent acute coronary syndrome
      have measurable coronary calcium because moderate-to-advanced coronary plaque
      disease is already present, although obstructive disease frequently is not.
      Prospective studies have demonstrated that extensive coronary calcium detected by
      EBCT is associated with a significantly increased incidence of subsequent
      myocardial infarction, need for revascularization, and coronary death. The
      incremental prognostic value of coronary calcium compared with that of risk
      factor assessment remains to be fully defined. The occurrence of an acute
      coronary syndrome is determined by many factors apart from the extent of
      atherosclerotic plaque disease. Large prospective trials in the general
      population are needed to define the subgroups that will benefit most from
      quantitative assessment of coronary calcium.

PMID- 11581150
TI  - Prevention and treatment of coronary heart disease: who benefits?
AB  - Coronary heart disease (CHD) remains a leading cause of morbidity and mortality
      in the United States, despite our better understanding of the pathobiology of
      atherosclerosis, our knowledge of risk factors, the widespread availability of
      inexpensive cholesterol screening, and the availability of effective and well
      tolerated cholesterol-lowering agents. Advances in these areas have created
      controversies regarding who should be screened and treated for primary or
      secondary prevention of coronary events. The advent of the statin class of lipid
      lowering agents represented a major advance, because they are much more effective
      and better tolerated than previous agents. There is general agreement that
      patients with hypercholesterolemia and established CHD require treatment for
      secondary prevention of recurrent coronary events. Primary prevention is
      controversial in all patient groups except those with diabetes, because their
      risk of developing CHD is dramatically increased. Postmenopausal women and the
      elderly are undertreated, whereas young adults may be underdiagnosed and
      undertreated. Several ongoing trials may resolve the controversies about which
      patient groups will benefit from different prevention and treatment strategies.

PMID- 11581151
TI  - Maffucci's syndrome.

PMID- 11581152
TI  - Exercise standards for testing and training: a statement for healthcare
      professionals from the American Heart Association.

PMID- 11581153
TI  - High-grade atrioventricular block caused by his-purkinje injury during contrast
      left ventriculography.

PMID- 11581154
TI  - Building better vasculature.

PMID- 11581155
TI  - Core promoters: active contributors to combinatorial gene regulation.

PMID- 11581156
TI  - Establishment of Polycomb silencing requires a transient interaction between PC
      and ESC.
AB  - Two distinct types of Polycomb complexes have been identified in flies and in
      vertebrates, one containing ESC and one containing PC. Using LexA fusions, we
      show that PC and ESC can establish silencing of a reporter gene but that each
      requires the presence of the other. In early embryonic extracts, we find PC
      transiently associated with ESC in a complex that includes EZ, PHO, PH, GAGA, and
      RPD3 but not PSC. In older embryos, PC is found in a complex including PH, PSC,
      GAGA, and RPD3, whereas ESC is in a separate complex including EZ, PHO, and RPD3.

PMID- 11581157
TI  - Enhancer-promoter specificity mediated by DPE or TATA core promoter motifs.
AB  - To investigate the basis for enhancer-promoter specificity, we compared the
      ability of enhancers to activate transcription in vivo from core promoters
      containing either downstream promoter element (DPE) or TATA box motifs. To
      eliminate position effects, we generated and analyzed pairs of sister Drosophila
      lines that contain a DPE- or TATA-dependent reporter gene at precisely the same
      genomic position relative to each enhancer. These studies revealed
      transcriptional enhancers that are specific for promoters that contain either DPE
      or TATA box elements. Thus, the core promoter not only mediates the initiation of
      transcription, but also functions as a regulatory element.

PMID- 11581158
TI  - Induction of hypervascularity without leakage or inflammation in transgenic mice
      overexpressing hypoxia-inducible factor-1alpha.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) transactivates genes required for
      energy metabolism and tissue perfusion and is necessary for embryonic development
      and tumor explant growth. HIF-1alpha is overexpressed during carcinogenesis,
      myocardial infarction, and wound healing; however, the biological consequences of
      HIF-1alpha overexpression are unknown. Here, transgenic mice expressing
      constitutively active HIF-1alpha in epidermis displayed a 66% increase in dermal
      capillaries, a 13-fold elevation of total vascular endothelial growth factor
      (VEGF) expression, and a six- to ninefold induction of each VEGF isoform. Despite
      marked induction of hypervascularity, HIF-1alpha did not induce edema,
      inflammation, or vascular leakage, phenotypes developing in transgenic mice
      overexpressing VEGF cDNA in skin. Remarkably, blood vessel leakage resistance
      induced by HIF-1alpha overexpression was not caused by up-regulation of
      angiopoietin-1 or angiopoietin-2. Hypervascularity induced by HIF-1alpha could
      improve therapy of tissue ischemia.

PMID- 11581159
TI  - Formation of brainstem (nor)adrenergic centers and first-order relay visceral
      sensory neurons is dependent on homeodomain protein Rnx/Tlx3.
AB  - Brainstem visceral sensory and (nor)adrenergic neurons play crucial roles in
      modulating cardiovascular and respiratory functions. The origins and formation of
      these neurons are poorly understood. Here we show that these two classes of
      neurons are derived from Mash1-positive precursor cells, and can be prospectively
      identified by combinatorial expression of two homeobox genes, Rnx and Phox2
      (Phox2a or Phox2b). It was previously shown that Rnx-deficient mice die from
      respiratory failure. Here we show that Rnx function is required for formation of
      first-order relay visceral sensory neurons in the brainstem. In addition, as in
      Phox2b-deficient mice, the development of most (nor)adrenergic centers is
      compromised in Rnx mutants. We also provide genetic evidence to show that Rnx and
      Phox2 proteins may function independently to specify the (nor)adrenergic
      phenotype. Our studies reveal a surprising ontogenetic relationship between relay
      visceral sensory and (nor)adrenergic neurons, and suggest that it may be a common
      theme in the developing nervous system that the same set of transcriptional
      regulators is associated with formation of multiple components within a neuronal
      network.

PMID- 11581160
TI  - The neuron-specific RNA-binding protein ELAV regulates neuroglian alternative
      splicing in neurons and binds directly to its pre-mRNA.
AB  - Drosophila melanogaster neural-specific protein, ELAV, has been shown to regulate
      the neural-specific splicing of three genes: neuroglian (nrg), erect wing, and
      armadillo. Alternative splicing of the nrg transcript involves alternative
      inclusion of a 3'-terminal exon. Here, using a minigene reporter, we show that
      the nrg alternatively spliced intron (nASI) has all the determinants required to
      recreate proper neural-specific RNA processing seen with the endogenous nrg
      transcript, including regulation by ELAV. An in vitro UV cross-linking assay
      revealed that ELAV from nuclear extracts cross-links to four distinct sites along
      the 3200 nucleotide long nASI; one EXS is positioned at the polypyrimidine tract
      of the default 3' splice site. ELAV cross-linking sites (EXSs) have in common
      long tracts of (U)-rich sequence rather than a precise consensus; moreover, each
      tract has at least two 8/10U elements; their importance is validated by mutant
      transgene reporter analysis. Further, we propose criteria for ELAV target
      sequence recognition based on the four EXSs, sites within the nASI that are (U)
      rich but do not cross-link with ELAV, and predicted EXSs from a phylogenetic
      comparison with Drosophila virilis nASI. These results suggest that ELAV
      regulates nrg alternative splicing by direct interaction with the nASI.

PMID- 11581161
TI  - A complex containing CstF-64 and the SL2 snRNP connects mRNA 3' end formation and
      trans-splicing in C. elegans operons.
AB  - Polycistronic pre-mRNAs from Caenorhabditis elegans are processed by 3' end
      formation of the upstream mRNA and SL2-specific trans-splicing of the downstream
      mRNA. These processes usually occur within an approximately 100-nucleotide region
      and are mechanistically coupled. In this paper, we report a complex in C. elegans
      extracts containing the 3' end formation protein CstF-64 and the SL2 snRNP. This
      complex, immunoprecipitated with alphaCstF-64 antibody, contains SL2 RNA, but not
      SL1 RNA or other U snRNAs. Using mutational analysis we have been able to
      uncouple SL2 snRNP function and identity. SL2 RNA with a mutation in stem/loop
      III is functional in vivo as a trans-splice donor, but fails to splice to SL2
      accepting trans-splice sites, suggesting that it has lost its identity as an SL2
      snRNP. Importantly, stem/loop III mutations prevent association of SL2 RNA with
      CstF-64. In contrast, a mutation in stem II that inactivates the SL2 snRNP still
      permits complex formation with CstF-64. Therefore, SL2 RNA stem/loop III is
      required for both SL2 identity and formation of a complex containing CstF-64, but
      not for trans-splicing. These results provide a molecular framework for the
      coupling of 3' end formation and trans-splicing in the processing of
      polycistronic pre-mRNAs from C. elegans operons.

PMID- 11581162
TI  - Drosophila separase is required for sister chromatid separation and binds to PIM
      and THR.
AB  - Drosophila PIM and THR are required for sister chromatid separation in mitosis
      and associate in vivo. Neither of these two proteins shares significant sequence
      similarity with known proteins. However, PIM has functional similarities with
      securin proteins. Like securin, PIM is degraded at the metaphase-to-anaphase
      transition and this degradation is required for sister chromatid separation.
      Securin binds and inhibits separase, a conserved cysteine endoprotease.
      Proteolysis of securin at the metaphase-to-anaphase transition activates
      separase, which degrades a conserved cohesin subunit, thereby allowing sister
      chromatid separation. To address whether PIM regulates separase activity or
      functions with THR in a distinct pathway, we have characterized a Drosophila
      separase homolog (SSE). SSE is an unusual member of the separase family. SSE is
      only about one-third the size of other separases and has a diverged endoprotease
      domain. However, our genetic analyses show that SSE is essential and required for
      sister chromatid separation during mitosis. Moreover, we show that SSE associates
      with both PIM and THR. Although our work shows that separase is required for
      sister chromatid separation in higher eukaryotes, in addition, it also indicates
      that the regulatory proteins have diverged to a surprising degree, particularly
      in Drosophila.

PMID- 11581163
TI  - Chloroplast DNA methylation and inheritance in Chlamydomonas.
AB  - When Chlamydomonas reinhardtii cells mate, a zygotic maturation program is
      activated, part of which leads to destruction of chloroplast DNA (cpDNA) from the
      mating type minus (mt-) parent, and, therefore, to uniparental inheritance of
      mating type plus (mt+) cpDNA. A long-standing model that explains the selective
      destruction of mt(-) cpDNA in zygotes invokes a methylation-restriction system.
      We tested this model by using the potent methylation inhibitor 5-aza-2'
      deoxycytidine (5adc) to hypomethylate parental cpDNA and found that the pattern
      of cpDNA inheritance is altered by 5adc in a manner that is consistent with the
      model. Surprisingly, however, hypomethylated mt+ cpDNA is not destroyed in
      zygotes as the methylation-restriction model predicts it should be. Destruction
      of mt- cpDNA is also unaffected when the parental mt+ cpDNA is hypomethylated.
      Instead, loss of methylation affects the relative rates of replication of
      residual mt- cpDNA and mt+ cpDNA in germinating zygotes. The mode of action for
      5adc on cpDNA replication in germinating zygotes may be via hypomethylation of
      mt+ cpDNA, but is also consistent with its action as a DNA-damaging agent.
      Interestingly, 5adc causes reduced cpDNA replication only in germinating zygotes,
      not in vegetatively grown cells, indicating that cpDNA replication is
      qualitatively different in these two stages of the life cycle. Our results
      demonstrate that methylation is not necessary for protection of the mt+ cpDNA in
      early zygotes and uncover a novel stage of the Chlamydomonas life cycle when
      replication of cpDNA is highly susceptible to perturbation. Our data support a
      model in which differential cpDNA replication in germinating zygotes is used as a
      mechanism to selectively amplify intact and properly methylated cpDNA molecules.

PMID- 11581164
TI  - Selective coactivation of estrogen-dependent transcription by CITED1 CBP/p300
      binding protein.
AB  - CITED1, a CBP/p300-binding nuclear protein that does not bind directly to DNA, is
      a transcriptional coregulator. Here, we show evidence that CITED1 functions as a
      selective coactivator for estrogen-dependent transcription. When transfected,
      CITED1 enhanced transcriptional activation by the ligand-binding/AF2 domain of
      both estrogen receptor-alpha (ERalpha) and ERbeta in an estrogen-dependent
      manner, but it affected transcriptional activities of other nuclear receptors
      only marginally. CITED1 bound directly to ERalpha in an estrogen-dependent manner
      through its transactivating domain, and this binding activity was separable from
      its p300-binding activity. CITED1 was strongly expressed in nulliparous mouse
      mammary epithelial cells and, when expressed in ER-positive MCF-7 breast cancer
      cells by transduction, exogenous CITED1 enhanced sensitivity of MCF-7 cells to
      estrogen, stabilizing the estrogen-dependent interaction between p300 and
      ERalpha. The estrogen-induced expression of the transforming growth factor-alpha
      (TGF-alpha) mRNA transcript was enhanced in the CITED1-expressing MCF-7 cells,
      whereas estrogen-induced expression of the mRNA transcripts for progesterone
      receptor or pS2 was not affected. Chromatin immunoprecipitation assay revealed
      that endogenous CITED1 is recruited to the chromosomal TGF-alpha promoter in MCF
      7 cells in an estrogen-dependent manner but not to the pS2 promoter. These
      results suggest that CITED1 may play roles in regulation of estrogen sensitivity
      in a gene-specific manner.

PMID- 11581166
TI  - The response in old mice: positive and negative immune memory after priming in
      early age.
AB  - To analyze the effect of age in both B and T cell compartments of the immune
      system, we have studied the anti-dextran (Dx) B512 humoral immune response in
      aged C57BL/6 mice. We have used Dx in its native form, which induces a thymus
      independent (TI) response, or conjugated to chicken serum albumin (CSA), which
      induces a thymus-dependent (TD) response. We have also analyzed the adjuvant
      effect of cholera toxin (CT) in both types of responses. Our results show that
      the B cell compartment is not greatly affected by age as demonstrated in the TI
      responses and that CT is a powerful adjuvant despite the age of the animals.
      However, we found a severe age-associated impairment of TD responses. We conclude
      that the first antigenic challenge deeply influences further antigenic responses
      in a positive or negative manner. Priming in early life with native Dx (TI)
      inhibited late TD responses in aged mice, even when the primary immunization had
      occurred a long time ago. This negative memory affects posterior TD responses
      both in the quantity and in the affinity of the response. However, immunization
      at an early age with TD priming (CSA-Dx) provoked a long-lasting immune memory
      that abolished in part the age-associated impairment of the response. Our results
      suggest that protocols of vaccination with TI antigens may not be a convenient
      strategy, because the development of further optimal immune responses to the same
      antigen can be impaired.

PMID- 11581167
TI  - Inhibition of mucosal and systemic T(h)2-type immune responses by intranasal
      peptides containing a dominant T cell epitope of the allergen Der p 1.
AB  - Although the intranasal administration of peptides containing T cell epitopes has
      been shown to be a potent method of inhibiting responses to the allergen Der p 1,
      the experiments to date have concentrated on their ability to regulate immune
      responses to the injection of antigen in a T(h)1-type adjuvant. Their ability to
      regulate responses to a T(h)2-type immunization and to sensitization via the
      respiratory mucosa has not been examined. Here it is shown that peptide used in
      doses required to block delayed-type hypersensitivity can also readily inhibit
      IgE responses to Der p 1 injected in alum. To examine responses induced in the
      respiratory mucosa, mice pretreated with intranasal peptide were sensitized with
      an intranasal dose of Der p 1 in conjunction with a mutated enterotoxin adjuvant.
      Intranasal peptide even in very high doses did not reduce IgE titers, but the
      ability of cells from the draining lymph nodes to release IL-4 and IL-13 but not
      IL-2, IL-5, IL-10 or IFN-gamma was reduced. These are the first reports on the
      effect of intranasal peptides containing T cell epitopes on IgE in T(h)2
      immunization and on responses to respiratory immunization. Thus the effect of the
      peptide-induced mucosal tolerance differs depending on the type of immunization
      used for sensitization, but the potential to inhibit T(h)2 responses and
      responses to respiratory sensitization as well as T(h)1 responses has been
      demonstrated.

PMID- 11581165
TI  - LAF1, a MYB transcription activator for phytochrome A signaling.
AB  - The photoreceptor phytochrome (phy) A has a well-defined role in regulating gene
      expression in response to specific light signals. Here, we describe a new
      Arabidopsis mutant, laf1 (long after far-red light 1) that has an elongated
      hypocotyl specifically under far-red light. Gene expression studies showed that
      laf1 has reduced responsiveness to continuous far-red light but retains wild-type
      responses to other light wavelengths. As far-red light is only perceived by phyA,
      our results suggest that LAF1 is specifically involved in phyA signal
      transduction. Further analyses revealed that laf1 is affected in a subset of phyA
      dependent responses and the phenotype is more severe at low far-red fluence
      rates. LAF1 encodes a nuclear protein with strong homology with the R2R3-MYB
      family of DNA-binding proteins. Experiments using yeast cells identified a
      transactivation domain in the C-terminal portion of the protein. LAF1 is
      constitutively targeted to the nucleus by signals in its N-terminal portion, and
      the full-length protein accumulates in distinct nuclear speckles. This
      accumulation in speckles is abolished by a point mutation in a lysine residue
      (K258R), which might serve as a modification site by a small ubiquitin-like
      protein (SUMO).

PMID- 11581168
TI  - Generation of cytotoxic T lymphocytes by MHC class I ligands fused to heat shock
      cognate protein 70.
AB  - Immunization with gp96 and heat shock cognate protein 70 (hsc70) purified with in
      vivo bound naturally occurring peptides or bound to synthetic peptides by in
      vitro reconstitution has been shown to induce peptide-specific cytotoxic T
      lymphocytes (CTL). In addition, mycobacterial heat shock protein 70 covalently
      fused to ovalbumin (OVA)-derived fragments has been shown to generate MHC class I
      restricted CTL responses. Here, we genetically fused five different CTL epitopes,
      including peptides derived from Plasmodium yoelii circumsporozoite protein, tumor
      antigens, HY antigen and OVA, to either the N- or C-terminus of murine hsc70 and
      expressed the resulting proteins in Escherichia coli. Vaccination with all five
      fusion proteins induced peptide-specific CTL, indicating that no cognate flanking
      regions of CTL epitopes are necessary for the immune response. The point of
      injection was crucial for CTL induction. CD4(+) T cells were not required for the
      priming of CD8(+) T cells and vaccination with bone marrow-derived dendritic
      cells pulsed with hsc70 fusion proteins also elicited CTL responses. Furthermore,
      by using deletion mutants of hsc70, we identified amino acid residues 280-385 of
      hsc70 as the region most critical for inducing the CTL response.

PMID- 11581169
TI  - Spatial and molecular organization of lymph node T cell cortex: a labyrinthine
      cavity bounded by an epithelium-like monolayer of fibroblastic reticular cells
      anchored to basement membrane-like extracellular matrix.
AB  - Naive T cells encounter antigen-presenting cells within the cortex of lymph nodes
      to initiate primary immune responses. Within this T cell cortex is the reticular
      network (RN)--a system of collagen fibers and extracellular matrix (ECM) wrapped
      by fibroblastic reticular cells (FRC). We have investigated the distribution of
      various molecules, including ECM proteins and proteoglycans, in the T cell cortex
      of both human and rodent lymph node. We confirm and extend reports of matrix
      elements in the RN. In addition, we find that staining for the laminin-alpha3
      chain and for tenascin reveals a 'hollow' reticular pattern, consistent with
      localization to the basement membrane-like covering of reticular fibers. In
      contrast, keratan sulfate is observed in a fine linear pattern within the RN,
      suggesting it is localized to the core of the fibers. Staining with the marker ER
      TR7 indicates that FRC cover all identifiable ECM surfaces of the T cell cortex.
      Based on these findings and previous reports, we conclude that cortical
      lymphocytes migrate within a 'labyrinthine cavity' free of fibrillar ECM,
      distinguishing the T cell cortex from other loose connective tissues, and that
      the FRC lining of the cavity constitutes an epithelium-like boundary. We propose
      that this spatial organization facilitates ameboid leukocyte crawling along
      preformed paths of least resistance and that the basement membrane-like ECM of
      the FRC may facilitate fluid transport within the RN by limiting leakage from the
      fiber.

PMID- 11581170
TI  - Proinflammatory cytokines induce liver and activation-regulated
      chemokine/macrophage inflammatory protein-3alpha/CCL20 in mucosal epithelial
      cells through NF-kappaB [correction of NK-kappaB].
AB  - Liver and activation-regulated chemokine (LARC)/CCL20 is expressed by surface
      lining epithelial and epidermal cells, and is likely to link innate and acquired
      immunity by attracting immature dendritic cells, effector memory T cells and B
      cells via CCR6. Here we examined the mechanism of LARC expression in epithelial
      type cells. Either IL-1beta or tumor necrosis factor (TNF)-alpha strongly induced
      LARC mRNA in intestinal cell lines Caco-2 and T84, while both were effective on
      HEK 293T cells. Induction of LARC was also demonstrated in the intestinal
      epithelium of BALB/c mice upon treatment with IL-1alpha or TNF-alpha. Transient
      transfection assays using murine LARC promoter-reporter constructs identified a
      region essential for IL-1beta- or TNF-alpha-induced promoter activation in Caco-2
      and 293T cells. Using site-directed mutagenesis, we demonstrated that an NF
      kappaB site located between -96 and -87 bp upstream from the transcriptional
      start site was both necessary and sufficient for IL-1beta- or TNF-alpha-induced
      promoter activation in Caco-2 and 293T cells. Electrophoretic mobility shift
      assays demonstrated that p50/p65 heterodimer and p65 homodimer of NF-kappaB bound
      to this site in 293T cells upon treatment with IL-1beta and TNF-alpha, and
      p50/p65 heterodimer bound to this site in Caco-2 cells upon treatment with IL
      1beta. Co-expression of constitutively active p65 strongly activated the promoter
      construct carrying the intact NF-kappaB site in 293T and Caco-2 cells.
      Collectively, LARC expression in intestinal epithelial-type cells is induced by
      proinflammatory cytokines such as IL-1 and TNF-alpha primarily through activation
      of NF-kappaB.

PMID- 11581171
TI  - Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain
      with karyopherin alpha (Rch1alpha).
AB  - We report a physical and functional association between the Tec-family tyrosine
      kinase Itk (Emt/Tsk) and the nuclear import chaperone karyopherin alpha
      (Rch1alpha) in human T cells. The Itk-SH3 domain and the Rch1alpha proline-rich
      (PR) motif were crucial for the Itk/Rch1alpha constitutive interaction as
      demonstrated by directed mutagenesis of the Rch1alpha PR motif (proline 242 to
      alanine, P242A). TCR-CD3 stimulation of Jurkat T cells resulted in increased
      Itk/Rch1alpha complex formation, recruitment of karyopherin beta to the protein
      complex and Rch1alpha tyrosine phosphorylation. Analysis of in vitro kinase
      reactions with a panel of recombinant glutathione-S-transferase (GST) fusion
      tyrosine kinases (Itk, Lck, ZAP-70 and Jak3) revealed that only GST-Itk
      efficiently phosphorylated a recombinant GST-Rch1alpha fusion. We observed
      constitutive nuclear localization of Itk that was up-regulated following either
      TCR-CD3 stimulation or over-expression of wild-type Rch1alpha in T cells.
      Further, nuclear localization of Itk and TCR-CD3-mediated IL-2 production were
      significantly down-regulated following expression of the Rch1alpha-P242A mutant,
      implicating a role for Rch1alpha in the nuclear translocation of Itk.

PMID- 11581172
TI  - Interactions of HLA-B27 with the peptide loading complex as revealed by heavy
      chain mutations.
AB  - MHC class I heavy chains assemble in the endoplasmic reticulum with beta(2)
      microglobulin and peptide to form heterotrimers. Although full assembly is
      required for stable class I molecules to be expressed on the cell surface, class
      I alleles can differ significantly in their rates of, and dependencies on, full
      assembly. Furthermore, these differences can account for class I allele-specific
      disparities in antigen presentation to T cells. Recent studies suggest that class
      I assembly is assisted by an elaborate complex of proteins in the endoplasmic
      reticulum, collectively referred to as the peptide loading complex. In this
      report we take a mutagenesis approach to define how HLA-B27 molecules interact
      with the peptide loading complex. Our results define subtle differences between
      how B27 mutants interact with tapasin (TPN) and calreticulin (CRT) in comparison
      to similar mutations in other mouse and human class I molecules. Furthermore,
      these disparate interactions seen among class I molecules allow us to propose a
      spatial model by which all class I molecules interact with TPN and CRT, two
      molecular chaperones implicated in facilitating the binding of high-affinity
      peptide ligands.

PMID- 11581173
TI  - Five mouse homologues of the human dendritic cell C-type lectin, DC-SIGN.
AB  - DC-SIGN, a human C-type lectin, is expressed on the surface of dendritic cells
      (DC), while a closely related human gene, DC-SIGNR or L-SIGN, is found on
      sinusoidal endothelial cells of liver and lymph node. Both DC-SIGN and DC-SIGNR/L
      SIGN can bind ICAM-3 and HIV gp120, and transmit HIV to susceptible cells in
      trans. Here, we report the cloning of five mouse genes homologous to human DC
      SIGN and DC-SIGNR/L-SIGN. Only one gene, named mouse DC-SIGN, is highly expressed
      in DC, and is not found in a panel of mouse macrophage and lymphocyte cell lines.
      The other four genes, named mouse SIGNR1 (SIGN-Related gene 1), SIGNR2, SIGNR3
      and SIGNR4, are expressed at lower levels in various cells according to RT-PCR
      and Northern blot analyses on RNA. All the genes of mouse DC-SIGN and SIGNRs map
      to adjacent regions of chromosome 8 A1.2-1.3. However, like human DC-SIGN, only
      the mouse DC-SIGN gene is closely juxtaposed to the CD23 gene, while the other
      four SIGNR genes are located close to each other in a neighboring region. mRNAs
      of mouse DC-SIGN and three SIGNR genes encode type II transmembrane proteins (DC
      SIGN, 238 amino acids; SIGNR1, 325 amino acids; SIGNR3, 237 amino acids; SIGNR4,
      208 amino acids), but the SIGNR2 gene only encodes a carbohydrate recognition
      domain (CRD) without a cytosolic domain and a transmembrane domain (SIGNR2, 178
      amino acids). Amino acid sequence similarities between the CRD of human DC-SIGN
      and the mouse homologues are 67% for DC-SIGN, 69% for SIGNR1, 65% for SIGNR2, 68%
      for SIGNR3 and 70% for SIGNR4 respectively. However, the membrane proximal neck
      domains in the mouse genes are much shorter than their counterparts in human DC
      SIGN and DC-SIGNR/L-SIGN. This family of mouse C-type lectins is therefore
      complex, but only one of the new genes, DC-SIGN, is juxtaposed to CD23 and is
      expressed at high levels in DC.

PMID- 11581174
TI  - In vivo staphylococcal superantigen-driven polyclonal Ig responses in mice:
      dependence upon CD4(+) cells and human MHC class II.
AB  - Staphylococcal enterotoxin (SE) B and seven other staphylococcal superantigens
      (SAg), despite promoting vigorous Ig production in human peripheral blood
      mononuclear cell cultures, are exceedingly poor at eliciting Ig responses in
      cultures of spleen cells from C57BL/10J (B10) or C3H/HeJ mice. In contrast, SEB
      elicits Ig responses in cultures of spleen cells from human MHC class II
      transgenic mice. Whereas i.p. administration of SEB (0.2-20 microg) to non
      transgenic B10 mice elicits very weak in vivo Ig responses, identical treatment
      of CD4(+) cell-intact (but not CD4(+) cell-depleted) human MHC class II
      transgenic mice elicits dramatic increases in both splenic Ig-secreting cells and
      serum Ig levels. Over a 2-week period, the SEB-induced in vivo Ig responses peak
      and then plateau or fall in association with a preferential increase in splenic
      CD8(+) cells. Nevertheless, in vivo depletion of CD8(+) cells has no sustained
      effect on SEB-driven Ig responses. Taken together, these observations demonstrate
      that the effects of SAg on in vivo humoral immune responses are highly CD4(+)
      cell dependent, are substantially CD8(+) cell independent and can be successfully
      investigated using human MHC class II-transgenic mice. This model system may be
      useful in investigating the polyclonally activating effects of microbial products
      (prototypic environmental insults) on the development of systemic autoimmunity.

PMID- 11581175
TI  - MHC class I molecules on adenovirus E1A-expressing tumor cells inhibit NK cell
      killing but not NK cell-mediated tumor rejection.
AB  - Expression of adenovirus E1A gene products in tumor cells enhances NK cell lysis
      in vitro and NK-mediated rejection in vivo, despite increasing class I molecules
      on tumor cells. It is unclear why the increased expression of MHC class I
      molecules does not appear to confer resistance to killing by NK cells. One
      possibility is the unique capacity of E1A to sensitize cells to multiple NK cell
      killing mechanisms including perforin/granzyme, Fas ligand, tumor necrosis factor
      alpha and TRAIL. To examine this issue, MCA-102-E1A tumor cells (H-2(b)) that
      express E1A and are NK sensitive were transfected with H-2D(d), the ligand for
      the NK inhibitory receptor, Ly49A. Expression of H-2D(d) molecules by MCA-102-E1A
      cells protected them from lysis by a Ly49A(+) NK cell clone and Ly49A(+) NK cells
      isolated from C57BL/6 nude mice. In contrast, NK cell-mediated rejection of MCA
      102-E1A tumor cells was not inhibited by the expression of H-2D(d) molecules, nor
      was killing by polyclonal populations of NK cells isolated from C57BL/6-nude
      mice. H-2D(d) interacts with several inhibitory Ly49 receptors that are non
      clonally expressed on NK cells in C57BL/6 mice: Ly49A (20% of NK cells), Ly49G2
      (54% of NK cells) and Ly49C/I (47% of NK cells). Our data indicate that while E1A
      sensitizes cells to NK cell killing, it does not interfere with signal
      transduction by inhibitory NK receptors. Therefore, a small population of NK
      cells that do not express Ly49A, Ly49G2 or Ly49C/I inhibitory receptors are
      likely responsible for the rejection of MCA-102-E1A-D(d) tumor cells in vivo.

PMID- 11581176
TI  - CD44 stimulation down-regulates Fas expression and Fas-mediated apoptosis of lung
      cancer cells.
AB  - Cytotoxic T lymphocytes (CTL) play a major role in the rejection of tumor cells,
      but tumor rejection does not always occur in vivo, indicating that defects in
      anti-tumor immune responses may be common. We here document a novel function for
      CD44--using lung cancer cells, we showed that stimulation of CD44 reduced Fas
      expression and Fas-mediated apoptosis: (i) lung cancer cells expressed high
      levels of CD44; (ii) engagement of CD44 on the cells by a specific antibody or
      fragmented hyaluronan reduced Fas expression; (iii) CD44 cross-linking reduced
      Fas-mediated apoptosis; (iv) stimulation of CD44 on lung cancer cells decreased
      IFN-gamma production by autologous CTL; and (v) CD44 stimulation prevented
      killing of lung cancer cells by autologous CTL. Based on these findings, we
      postulate a new concept--that interaction of CD44 on lung cancer cells with
      fragments of extracellular hyaluronan present in the surrounding extracellular
      matrix reduces Fas expression as well as Fas-mediated apoptosis of cancer cells.
      This leads to reduced susceptibility of the cells to CTL-mediated cytotoxicity
      through the Fas-Fas ligand pathway.

PMID- 11581177
TI  - Relative resistance to nasally induced tolerance in non-obese diabetic mice but
      not other I-A(g7)-expressing mouse strains.
AB  - I-A(g7) is a unique class II MHC molecule that is clearly associated with
      autoimmune diabetes in non-obese diabetic (NOD) mice. To determine if I-A(g7) is
      defective in its ability to deliver tolerogenic signals in vivo, H-2(g7) mice
      were nasally pretreated with antigen, prior to immunization, to induce antigen
      specific regulation. Nasally pretreated NOR (H-2(g7)) and (NON).NOD (H-2(g7))
      congenic mice showed responses similar to those of NON (H-2(nb1)), BALB/c (H
      2(d)) and B10.PL (H-2(u)) mice-a reduced recall response and a deviated T(h)
      cytokine profile. However, we found that NOD (H-2(g7)) mice are comparatively
      resistant to immunological tolerance induced by nasal pretreatment, such that at
      the usually effective dose no significant reduction was seen in the proliferative
      recall responses to nominal antigen after immunization. (NOD x BALB/c)F(1) (H
      2(g7/d)) and (NOD x NOR)F(1) (H-2(g7)) mice were similarly resistant to nasal
      induced tolerance, although significantly higher nasal doses of antigen were able
      to overcome the resistance in NOD and F(1) mice. Interestingly, activated NOD T
      cells were resistant to cell death induced by re-stimulation with plate-bound
      anti-CD3. These results demonstrate that activated T cells in NOD mice are
      defective in their ability to respond to regulatory signals delivered in vivo or
      in vitro. Furthermore, NOD T cells have an increased resistance to tolerance
      induced by I-A(g7)-dependent (antigen) or I-A(g7)-independent (anti-CD3)
      mechanisms. Thus, while I-A(g7) may contribute to insulin-dependent diabetes
      mellitus by selecting a particular repertoire of self-reactive T cell clones,
      additional defects in the peripheral T cells themselves are required to allow the
      expansion of diabetogenic clones and the development of autoimmune disease.

PMID- 11581178
TI  - Antibody levels to the class I and II epitopes of the M protein and myosin are
      related to group A streptococcal exposure in endemic populations.
AB  - Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal
      glomerulonephritis are thought to be autoimmune diseases, and follow group A
      streptococcal (GAS) infection. Different GAS M types have been associated with
      rheumatogenicity or nephritogenicity and categorized into either of two distinct
      classes (I or II) based on amino acid sequences present within the repeat region
      ('C' repeats) of the M protein. Sera from ARF patients have previously been shown
      to contain elevated levels of antibodies to the class I-specific epitope and
      myosin with the class I-specific antibodies also being cross-reactive to myosin,
      suggesting a disease association. This study shows that immunoreactivity of the
      class I-specific peptide and myosin does not differ between controls and acute RF
      (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility
      that the association is related to GAS exposure, not the presence of ARF/RHD.
      Peptide inhibition studies suggest that the class I epitope may be conformational
      and residue 10 of the peptide is critical for antibody binding. We demonstrate
      that correlation of antibody levels between the class I and II epitope is due to
      class II-specific antibodies recognizing a common epitope with class I which is
      contained within the sequence RDL-ASRE. Our results suggest that antibody
      prevalence to class I and II epitopes and myosin is associated with GAS exposure,
      and that antibodies to these epitopes are not an indicator of disease nor a
      pathogenic factor in endemic populations.

PMID- 11581179
TI  - Expression of serine protease inhibitor 3 in ocular tissues in endotoxin-induced
      uveitis in rat.
AB  - PURPOSE: To ascribe the serine protease inhibitor 3 (SPI-3) as an ocular acute
      inflammatory molecule and to clarify its producing cells in an endotoxin-induced
      uveitis (EIU) model. METHODS: Male Wistar rats were injected with
      lipopolysaccharide (LPS), and the expression of SPI-3 mRNA in the ocular tissues
      was examined by in situ hybridization (ISH) and Northern blot analysis. A
      combination of ISH and immunohistochemistry (IHC) were performed to prove the
      colocalization of SPI-3 mRNA and either glial fibrillary acidic protein (GFAP) or
      OX-42. The expression of phosphorylated STAT3 (pSTAT3) was demonstrated by IHC
      and Western blot after LPS injection. The colocalization of SPI-3 mRNA and pSTAT3
      was finally examined by the double labeling of ISH and IHC. RESULTS: After LPS
      injection, the expression of SPI-3 mRNA in ocular tissues was quickly upregulated
      and reached a peak between 12 and 24 hours after injection. An intense mRNA
      signal was observed in epithelial cells of the iris and ciliary body and the
      innermost retinal layer. In the retina, SPI-3 mRNA was colocalized with GFAP,
      demonstrating that the cells expressing SPI-3 mRNA were astrocytes. After LPS
      treatment, SPI-3 mRNA and pSTAT3 were colocalized in retinal astrocytes, and
      pSTAT3 expression appeared slightly earlier than that of SPI-3 mRNA. CONCLUSIONS:
      Ocular inflammation induced the transient expression of SPI-3 mRNA in retinal
      astrocytes and epithelial cells in the iris and ciliary body, particularly during
      early phase of the inflammation. Simultaneously, the activation of STAT3
      (phosphorylation of STAT3) occurred slightly earlier in astrocytes. This supports
      the previous in vitro results that SPI-3 expression is induced in a STAT3
      mediated manner. SPI-3 may have some crucial roles in preventing some
      degenerative proteolysis, which is induced by inflammatory stimuli.

PMID- 11581180
TI  - Parasympathetic innervation of the meibomian glands in rats.
AB  - PURPOSE: To determine the location of parasympathetic neurons that innervate the
      meibomian glands in rats. METHODS: The B subunit of cholera toxin (CTB), fast
      blue, and a retrograde transneuronal tracer, the Bartha strain of pseudorabies
      virus (PRV-Ba), were injected into the upper eyelids of adult Sprague-Dawley rats
      after sectioning the ipsilateral branches of the facial nerve and resecting the
      superior cervical ganglia. Brains and orbital tissues were processed for the
      immunohistochemical detection of PRV-Ba and CTB. In selected cases, series of
      brain sections were double labeled for PRV-Ba and tyrosine hydroxylase to
      determine the relationship between the A5 noradrenergic cell group and superior
      salivatory nucleus, or for PRV-Ba and choline acetyltransferase to establish the
      neurochemical phenotype of parasympathetic preganglionic neurons. RESULTS:
      Labeled ganglionic cells were diffusely distributed within the ipsilateral
      pterygopalatine ganglion (PPG) and along the more proximal portions of the
      greater petrosal nerve (GPN). Labeled preganglionic neurons were cholinergic and
      were located immediately dorsolateral to the rostral-most portion of the facial
      nucleus and caudal superior olive, where they intermingled with A5 noradrenergic
      cells. CONCLUSIONS: The meibomian glands and other structures within the lid
      margin are subject to parasympathetic regulation by ganglion cells diffusely
      distributed within the PPG and along more proximal portions of the GPN.
      Cholinergic parasympathetic preganglionic neurons that project to meibomian gland
      innervating ganglion cells are located immediately lateral, dorsal, and rostral
      to the facial motor nucleus in the region commonly referred to as the superior
      salivatory nucleus.

PMID- 11581181
TI  - Ezrin as a prognostic indicator and its relationship to tumor characteristics in
      uveal malignant melanoma.
AB  - PURPOSE: Immunohistochemistry was used to investigate whether uveal malignant
      melanoma expresses ezrin, a protein involved in cell migration and cell
      recognition by acting as a linker between the plasma membrane and actin
      cytoskeleton. Also investigated was whether ezrin immunoreactivity correlates
      with survival prognosis. METHODS: A monoclonal antibody, 3C12, that reacts with
      the carboxyl-terminal part of ezrin was used in retrospective analysis of a
      population-based cohort of 167 consecutive choroidal and ciliary body melanomas
      in eyes enucleated from 1972 through 1981, with a median follow-up of 22 years.
      RESULTS: Ezrin immunoreactivity in tumor cells was graded negative in 47 (36%)
      melanomas, positive in 74 (57%), and strongly positive in 9 (7%). The
      immunoreactivity tended to be homogenous throughout the tumor, with focal
      concentrations along the cell surface. Positive reaction was significantly
      associated with high microvascular density (P < 0.001) and presence of
      macrophages (P < 0.001), but not with tumor size, cell type, or microvascular
      loops and networks. The 10-year melanoma-specific survival was significantly
      associated with ezrin immunoreactivity (P = 0.018). After adjustment by Cox
      regression for tumor size, cell type, microvascular loops and networks, and
      microvascular density, a clinically meaningful 0.15 difference in 10-year
      melanoma-specific survival persisted. CONCLUSIONS: The presence of ezrin
      immunoreactivity in uveal malignant melanoma is associated with higher mortality
      and with two independent high-risk characteristics: microvascular density and
      number of infiltrating macrophages. Further experimental studies on the
      interrelationship of these three factors may shed light on the progression of
      uveal melanoma and perhaps that of other cancers.

PMID- 11581182
TI  - Immunoglobulin heavy chain gene analysis of ocular adnexal extranodal marginal
      zone B-cell lymphoma.
AB  - PURPOSE: To clarify the cellular origin of extranodal marginal-zone B-cell
      lymphoma (EZML) of the mucosa-associated lymphoid tissue (MALT) type in ocular
      adnexa, the somatic mutation was analyzed in the immunoglobulin heavy-chain
      variable region (VH) gene. METHODS: Eight cases of EZML in the orbit and four in
      the conjunctiva were studied. The VH genes were amplified by a seminested PCR and
      sequenced directly. These were compared with the closest published VH germline
      segments to determine the somatic mutation frequency. Intraclonal
      microheterogeneity, which was termed the ongoing mutation frequency in the
      current study, was estimated by counting the number of single nucleotide
      substitutions in individual clones and dividing by the total number of
      nucleotides analyzed. Nine cases of gastrointestinal EMZL were also examined for
      comparison. RESULTS: The somatic mutation frequency varied between 2.0% and
      12.7%, with a mean value of 7.9%. Ten cases with intraclonal microheterogeneity
      showed between one and six further substitutions. The average of ongoing mutation
      frequency was 0.11%, with a range of 0% to 0.25%. In the gastrointestinal EMZLs,
      the average of somatic mutation frequency was 8.5% (1.5%-14.2%) and of ongoing
      mutation frequency was 0.51% (0.25%-0.75%). CONCLUSIONS: The average of ongoing
      mutation frequency in ocular adnexal EMZL was lower than that in gastrointestinal
      EMZL. Both ocular adnexal and gastrointestinal EMZLs are derived from
      postgerminal center memory B cells, but the low ongoing mutation frequencies of
      ocular adnexal EMZL may result from less antigen stimulation and follicular
      colonization in the orbit relative to gastrointestinal EMZL.

PMID- 11581183
TI  - CORD9 a new locus for arCRD: mapping to 8p11, estimation of frequency, evaluation
      of a candidate gene.
AB  - PURPOSE: To determine the locus of the mutant gene causing autosomal recessive
      cone-rod dystrophy (arCRD) in a consanguineous pedigree, to evaluate a candidate
      gene expressed in retina that maps to this locus, and to estimate the percentage
      of arCRD cases caused by mutations in this gene. METHODS: DNAs from family
      members were genotyped for markers covering the entire genome at an average
      spacing of approximately 9 centimorgans (cM). The data were input into a pedigree
      computer program to produce output files used to calculate lod scores.
      Significant linkage was revealed at 8cen, prompting the genotyping of a number of
      additional markers. Exons of a candidate gene were sequenced directly by standard
      fluorescent dideoxy methods. Haplotype analysis was performed with markers in
      this locus in 13 multiplex and 2 simplex CRD families in which neither parent had
      disease. RESULTS: Four-point linkage analysis gave a maximum lod score of
      approximately 7.6 at both D8S1769 and GATA101H09 in the large consanguineous
      family. Recombination events defined an interval of 8.7 cM between D8S1820 and
      D8S532 within which the gene must lie. This 8p11 locus (CORD9) is immediately
      distal to but distinct from the RP1 autosomal dominant RP (adRP) locus. Two
      islands of homozygosity were found in this locus: The alleles of 6 of 10 markers
      in one of the islands and 2 of 4 in the other were homozygous. The UniGene
      cluster Hs.8719 (UniGene System, provided by the National Center for
      Biotechnology Information and available at http://www.ncbi.nlm.nih.gov/UniGene),
      which tags a gene with significant homology to Dual Specificity Phosphatase 3,
      maps within the CORD9 interval and is highly expressed in the retina. To evaluate
      this gene as a potential disease candidate, intron-exon structure was determined,
      and exons were screened in the consanguineous family. No variants were found that
      could be related to disease. Haplotype analysis of 15 other families with CRD,
      using markers at CORD9, excluded this locus in 9 of 15. CONCLUSIONS: A new arCRD
      locus (CORD9) has been identified corresponding to a yet unidentified gene in the
      8.7-cM interval D8S1820-D8S532. No mutations were found in one candidate gene in
      affected members of the primary study family. Haplotype analysis of a cohort of
      13 multiplex and 2 simplex families with CRD ruled out the CORD9 gene in 9 of 15
      of the families. To date, a total of 126 loci carrying gene mutations causing
      various forms of retinal degeneration have been mapped, and the mutant gene has
      been identified in 64 of them. However, only 2 loci for arCRD have been
      documented. This is the report of a third.

PMID- 11581184
TI  - Fine mapping of canine XLPRA establishes homology of the human and canine RP3
      intervals.
AB  - PURPOSE: Canine X-linked progressive retinal atrophy (XLPRA) is a hereditary,
      progressive retinal degeneration that has been mapped previously to the canine X
      chromosome in a region flanked by the dystrophin (DMD) and tissue inhibitor of
      metalloproteinase 1 (TIMP1) genes, and is tightly linked to the gene RPGR. The
      comparable region of the human X chromosome includes the disease locus for RP3,
      an X-linked form of retinitis pigmentosa, although the current canine disease
      interval is much larger. METHODS: To refine the map of the canine XLPRA disease
      interval, 11 X-linked markers were mapped, both meiotically, in two extensive
      canine pedigrees informative for XLPRA, and on a 3000-rad canine-hamster
      radiation hybrid (RH) panel. A 12th marker was mapped on the RH panel alone.
      RESULTS: The integrated map of this region of CFAX now covers approximately 47.3
      centimorgans (cM) and 194 centirays (cR)(3000), and demonstrates strong
      conservation of synteny between humans and dogs. Genes defining the human RP3
      zero-recombination interval (human homologue of mouse t complex [TCTE1L], sushi
      repeat-containing protein, X chromosome [SRPX], and retinitis pigmentosa
      guanosine triphosphatase [GTPase] regulator [RPGR]) are tightly linked to each
      other, to the XLPRA locus, and to the gene ornithine transcarbamylase (OTC) in
      dogs. CONCLUSIONS: Strong conservation of gene order was demonstrated in the
      short arm of the X chromosome between dogs and humans as was homology of the
      canine XLPRA and human RP3 intervals. These results create a valuable tool for
      investigating canine XLPRA and other X-linked eye diseases in dogs.

PMID- 11581185
TI  - Loss of heterozygosity on chromosomes 3, 9, 13, and 17, including the
      retinoblastoma locus, in uveal melanoma.
AB  - PURPOSE: To identify tumor-suppressor loci that may contribute to the
      pathogenesis of uveal melanoma. METHODS: Multiplex fluorescence microsatellite
      assays were performed on 27 uveal melanomas using markers at 3p25-p26, 3p14.2,
      9p21-p23, 13q14, 13q12.3-q13, and 17p13, close to or within the von Hippel Lindau
      (VHL), fragile histidine triad (FHIT), p16/cyclin-dependent kinase inhibitor 2
      (CDKN2A), retinoblastoma (RB1), breast cancer 2 (BRCA2), and p53 tumor suppressor
      loci, respectively. Further markers on chromosomes 3 and 9 were analyzed
      individually. RESULTS: Loss of heterozygosity (LOH) was identified in 63% of
      tumors, most frequently on chromosome 3 (52%), in association with epithelioid
      cells (P = 0.0002) and microvascular loops (P = 0.0008). In the majority of
      cases, LOH on chromosome 3 was detected at all informative markers. The second
      most common alteration was LOH at an RB1 intragenic marker (21% tumors), with
      retention of a more centromeric 13q marker (near BRCA2). The pattern of LOH on
      chromosome 9p was consistent with the involvement of a region telomeric to
      CDKN2A. LOH at TP53 was infrequent. CONCLUSIONS: In the majority of cases,
      chromosome 3 LOH involves an entire chromosome homologue, which hampers
      identification of the relevant suppressor loci. This LOH correlates with the
      presence of microvascular loops and epithelioid cells, two of the recognized
      histologic indicators of poor prognosis. Data for chromosomes 13 and 9 support a
      role for RB1 in the pathogenesis of uveal melanoma but also raise the possibility
      of the involvement of additional loci close to RB1 and CDKN2A.

PMID- 11581186
TI  - Prevalence of the different types of age-related cataract in an African
      population.
AB  - PURPOSE: To describe the prevalence of different types of cataract and their
      association with visual acuity in a Tanzanian population aged 40 years and older.
      METHODS: A prevalence survey for lens opacity, glaucoma, and visual impairment
      was carried out on all residents age 40 and older of six villages in Kongwa,
      Tanzania. One examiner graded the lens for presence of nuclear (NSC), posterior
      subcapsular (PSC), and cortical cataract (CC), using the new WHO Simplified
      Cataract Grading System. Visual acuity was measured in each eye, both presenting
      and best corrected, using an illiterate E chart. RESULTS: The proportion of
      eligible subjects participating was 90% (3268/3641). The prevalence of cataract
      was as follows: NSC, 15.6%; CC, 8.8%; and PSC, 1.9%. All types of cataract
      increased with age, from NSC, 1.7%; CC, 2.4%; and PSC, 0.4% for those aged 40 to
      49 years to NSC, 59.2%; CC, 23.5%; and PSC, 5.9% for those aged 70 years and
      older (P < 0.0001 for all cataract types, chi(2) test for trend). Cataract
      prevalence was higher among women than men for NSC (P = 0.0001), but not for CC
      (P = 0.15) or PSC (P = 0.25), after adjusting for age. Prevalence rates of visual
      impairment (BCVA < 6/12), US blindness (< or = 6/60) and WHO blindness (< 6/120)
      for this population were 13.3%, 2.1%, and 1.3%, respectively. Older age and each
      of the major types of pure and mixed cataract were independently associated with
      worse vision in regression modeling. CONCLUSIONS: Unlike African-derived
      populations in Salisbury and Barbados, NSC rather than CC was most prevalent in
      this African population. The seeming lower prevalence of CC may to some extent be
      explained by different grading schemes, differential availability of cataract
      surgery, the younger mean age of the Tanzanian subjects, and a higher prevalence
      of NSC in this population.

PMID- 11581187
TI  - Alteration in goblet cell numbers and mucin gene expression in a mouse model of
      allergic conjunctivitis.
AB  - PURPOSE: To determine whether the number of filled conjunctival goblet cells and
      mucin gene expression are altered in a mouse model of allergic conjunctivitis.
      METHODS: A/J mice were sensitized intraperitoneally with cat dander or the
      peptide P3-1 from the protein Fel d1. Two weeks later, the mice were challenged
      for 7 consecutive days with eye drops containing the allergens. Conjunctival
      tissue was harvested at 0, 6, 24, or 48 hours after final antigen challenge.
      Control samples were naive animals and mice sensitized with cat dander and
      challenged with OVA-peptide or PBS. The mean number of filled goblet cells per
      square millimeter in three forniceal fields for each group was determined in
      wholemounts of conjunctiva prepared using rhodamine-phalloidin labeling followed
      by confocal microscopy. RNA was isolated from conjunctiva of the contralateral
      eye and taken for relative quantitation of mRNA of the goblet cell mucin Muc5AC
      and the epithelial membrane-spanning mucin Muc4, by real-time RT-PCR. RESULTS:
      The number of filled goblet cells was significantly decreased with both cat
      dander and P3-1, after final ocular challenge (P < 0.001). The most significant
      decrease over naive mice was seen at 6 hours after final challenge with both
      allergens. The number of filled goblet cells was still decreased but was
      returning toward naive levels at 24 hours (P < 0.05), and at 48 hours no
      significant difference was seen compared with naive, PBS-treated, and OVA-peptide
      treated control samples. For both cat dander and P3-1, Muc5AC and Muc4 mRNA was
      found to be decreased at the time of final ocular challenge. The level of Muc5AC
      mRNA from goblet cells rebounded from the decrease to show an increase over
      control by 24 hours after final challenge, and by 48 hours, the mRNA level had
      returned to naive control range. In contrast, significant increases in Muc5AC
      mRNA were evident after final control challenge with PBS or OVA-peptide,
      indicating a potential irritant effect of drop application. The Muc4 mRNA level
      was significantly reduced at all time points except 24 hours after the last
      challenge. By comparison with allergen-challenged eyes, no change in Muc4 message
      levels was noted at any time point in OVA-peptide- or PBS-treated control eyes.
      CONCLUSIONS: These findings demonstrate that, in the conjunctiva of mice,
      repetitive application of allergens induces a reduction in the number of filled
      goblet cells and a decrease in Muc5AC and Muc4 mRNAs. After a period of 24 to 48
      hours, the goblet cell number return to naive levels, and goblet cell mucin mRNA
      levels return to above or within normal range, indicating a rapid recovery in the
      mucus secretion system.

PMID- 11581188
TI  - Fibroblast growth factor reversal of the corneal myofibroblast phenotype.
AB  - PURPOSE: Keratocytes give rise to fibroblasts and myofibroblasts in wounded
      cornea. It is well established that treatment of fibroblasts with transforming
      growth factor (TGF) beta will induce myofibroblast differentiation. We
      investigated whether this differentiation could be reversed by the administration
      of fibroblast growth factor (FGF). METHODS: Cultured corneal myofibroblasts were
      plated at 200 cells/mm(2), and cells were grown in DMEM/F12 containing (1) 10%
      FBS or (2) 10% FBS with FGF and heparin or (3) 1% FBS or (4) 1% FBS with TGF
      beta. As distinguished from the fibroblast phenotype, the myofibroblast phenotype
      was identified by the assembly of alpha-smooth muscle (SM) actin protein into the
      stress fiber cytoskeleton. To further characterize growth factor regulation of
      the two phenotypes, the phenotypic expression of TGF-beta receptor types I and
      II, cadherins, and connexin 43 by immunocytochemistry, Western blot analysis, and
      immunoprecipitation and of alpha-SM actin mRNA in Northern blot analysis were
      evaluated. RESULTS: Corneal myofibroblasts replated and grown in the presence of
      FGF-1 or FGF-2 (20 ng/ml) plus heparin (5 microg/ml) in 10% FBS medium had
      decreased expression of alpha-SM actin protein, TGF-beta receptors, and
      cadherins. Thus, FGF-heparin decreased the myofibroblast phenotype and promoted
      the fibroblast phenotype. Administration of either 20 ng/ml FGF or 5 microg/ml
      heparin alone was not effective. Addition of TGF-beta further enhanced the
      expression of alpha-SM actin mRNA and protein and cell surface expression of TGF
      beta receptors in myofibroblast cultures. CONCLUSIONS: FGF-1 or -2 and heparin
      promoted the fibroblast phenotype and reversed the myofibroblast phenotype. This
      finding supports the idea that corneal myofibroblasts and fibroblasts are
      alternative phenotypes rather than terminally differentiated cell types.

PMID- 11581189
TI  - Glial cell-derived neurotrophic factor (GDNF)-induced migration and signal
      transduction in corneal epithelial cells.
AB  - PURPOSE: To identify signal-transduction pathways induced by glial cell-derived
      neurotrophic factor (GDNF) in corneal epithelial cells and to characterize its
      effect on cell migration. METHODS: Expression of GDNF receptor (GFR) alpha-1 in
      human corneal epithelium was detected by RT-PCR and Western blot analysis.
      Expression and phosphorylation of Ret, activation of focal adhesion kinase (FAK)
      and mitogen-associated protein kinase (MAPK) signaling pathways, and
      phosphorylation of paxillin by GDNF were investigated by immunoprecipitation and
      Western blot analysis in primary human corneal epithelial cells and a corneal
      epithelial cell line. The tyrosine kinase inhibitor herbimycin A and Ras
      farnesyltransferase inhibitor manumycin were used to specifically inhibit GDNF
      induced signaling pathways. In vitro wound-healing assays and modified Boyden
      chamber analysis were performed to investigate the effect of GDNF on epithelial
      cell migration. RESULTS: Expression of GFRalpha-1 was detected in normal and
      transformed human corneal epithelium. GDNF induced tyrosine phosphorylation of
      Ret. Furthermore, tyrosine phosphorylation of FAK and phosphotyrosine kinase
      (Pyk) 2; serine phosphorylation of c-Raf, MEK1, and Elk 1; and tyrosine-threonine
      phosphorylation of Erk-1 and -2 were time-dependently activated in the presence
      of GDNF. Tyrosine phosphorylation of paxillin was also induced by GDNF. Migration
      of corneal epithelial cells was significantly stimulated by GDNF. Herbimycin A
      strongly inhibited the activation of Ret, FAK, c-Raf, and Erk-1 and -2; the
      phosphorylation of paxillin; and corneal epithelial cell migration. More
      specifically, the Ras inhibitor manumycin inhibited phosphorylation of c-Raf, MEK
      1, Erk-1 and -2, and Elk 1, but not that of FAK. CONCLUSIONS: Corneal epithelial
      cells express receptors specific for GDNF that are used by GDNF to induce
      intracellular signaling. FAK and MAPK pathways seem to be activated by GDNF to
      modulate gene transcription and cell migration. FAK seems to be an upstream
      regulator of the MAPK cascade for GDNF signal transduction. As an inducer of FAK
      dependent corneal epithelial migration, GDNF may play an important role in
      corneal regeneration and wound healing.

PMID- 11581190
TI  - Effect of Fas and Fas ligand deficiency in resistance of C57BL/6 mice to HSV-1
      keratitis and chorioretinitis.
AB  - PURPOSE: To investigate the effect of Fas and Fas ligand (FasL) deficiency on the
      development of herpes stromal keratitis and on the von Szily model of herpes
      retinitis in C57BL/6 mice, which are ordinarily resistant to development of both
      of these herpetic diseases. METHODS: Anterior chamber inoculation of the right
      eye of each mouse with various titers of HSV-1 (KOS strain) was performed. Both
      eyes of each mouse were enucleated on postinoculation day 15 and processed for
      histopathologic examination. HSV-1 was inoculated into one cornea of other mice,
      and the severity of stromal keratitis was scored. RESULTS: Contralateral
      destructive chorioretinitis developed in susceptible Balb/cByj mice (19/23);
      ipsilateral chorioretinitis did not occur (0/23). Stromal keratitis developed in
      susceptible C.AL-20 mice (15/16). None of the C57BL/6 (0/10 for keratitis or 0/20
      for retinitis) developed inflammation. Neither did B6.SMN.C3H.gld (FasL
      deficient; 0/12 or 0/28) or B6.MRL.lpr (Fas deficient; 0/11 or 0/34) mice
      (keratitis or contralateral chorioretinitis). Minimal scattering of inflammatory
      cells in the contralateral retina but not destructive chorioretinitis was
      observed in two C57BL/6, three B6.SMN.C3H.gld, and five B6.MRL.lpr mice. Few
      inflammatory cells were also found in the ipsilateral vitreous and vitreoretinal
      interface (but not destructive chorioretinitis) of all C57BL/6, two gld, and
      three lpr mice. CONCLUSIONS: Immune dysregulation secondary to deficiency in Fas
      or FasL system does not influence the resistance of the C57BL/6 mice to develop
      herpes simplex keratitis or destructive herpes simplex chorioretinitis.

PMID- 11581191
TI  - Inhibition of inflammatory corneal angiogenesis by TNP-470.
AB  - PURPOSE: To determine the efficacy of the angiogenic inhibitor TNP-470 on
      inflammatory corneal neovascularization. Topical and systemic delivery of the
      drug were investigated in a murine model as well as inhibition of endothelial
      cell proliferation in vitro and in vivo. METHODS: The effect of TNP-470 on VEGF-
      and bFGF-stimulated bovine capillary endothelial (BCE) cell proliferation was
      evaluated in vitro. Corneal neovascularization was induced in vivo by mechanical
      debridement of the corneal and limbal epithelium with 0.15 M NaOH on C57BL6 mice.
      TNP-470 was administered systemically at 30 mg/kg body weight (BW) every other
      day or topically three times daily in a concentration of 5 ng/ml dissolved in
      methylcellulose. Vessel length was investigated on day 7. VEGF protein content in
      murine corneas was analyzed by ELISA on days 2, 4, and 7 of treatment. A modified
      bromouridine (BrdU) ELISA was used to quantify endothelial cell proliferation.
      RESULTS: TNP-470 exerted a dose-dependent inhibition of bFGF- and VEGF-induced
      endothelial cell proliferation in vitro. Both systemic and topical application of
      TNP-470 led to a significant reduction of inflammatory corneal neovascularization
      (P < 1 x 10(-5)). BrdU labeling showed that TNP-470 inhibited endothelial cell
      proliferation. VEGF protein levels were reduced by systemic TNP-470 treatment.
      CONCLUSIONS: These results suggest that TNP-470 reduces inflammatory corneal
      angiogenesis by directly inhibiting endothelial cell proliferation. Topical and
      systemic treatment with TNP-470 reduces VEGF levels that are responsible for
      vessel growth during the neovascularization process.

PMID- 11581192
TI  - Matrilysin cleavage of corneal collagen type XVIII NC1 domain and generation of a
      28-kDa fragment.
AB  - PURPOSE: To localize endostatin and collagen type XVIII in human corneas and to
      characterize the enzymatic action of matrix metalloproteinases (MMPs) in the
      cleavage of collagen type XVIII and generation of endostatin in the cornea.
      METHODS: Anti-endostatin and anti-hinge antibodies were generated using peptide
      fragments corresponding to the endostatin region and the adjacent nonendostatin
      hinge region of collagen XVIII noncollagenous (NC)1 domain, respectively.
      Confocal immunostaining was performed to localize collagen XVIII in human
      corneas. SV40-immortalized corneal epithelial cells were immunoprecipitated and
      incubated with active MMP-1, -2, -3, -7, or -9, and Western blot analysis was
      performed to study collagen XVIII cleavage. Incubation with MMP-7 was performed
      at various concentrations (0, 2, 4, and 6 microg/ml) and time intervals (0, 1, 5,
      and 12 hours). Purified recombinant NC1 fragment of collagen XVIII was also
      digested with MMP-7, and the cleavage product was sequenced. RESULTS: Collagen
      XVIII was immunolocalized to the human corneal epithelium, epithelial basement
      membrane, and Descemet membrane. Western blot analysis demonstrated a 180- to 200
      kDa band corresponding to collagen XVIII. MMP-7 (but not MMP-1, -2, -3, and -9)
      cleaved corneal epithelium-derived collagen XVIII to generate a 28-kDa endostatin
      spanning fragment in a time- and concentration-dependent fashion. MMP-7 cleaved
      purified recombinant 34-kDa NC1 fragment of collagen XVIII in the hinge region to
      generate a 28-kDa fragment. CONCLUSIONS: Collagen XVIII is present in human
      cornea. MMP-7 cleaves the collagen XVIII NC1 domain to generate a 28-kDa fragment
      in the cornea.

PMID- 11581193
TI  - Mitochondrial activity and glutathione injury in apoptosis induced by unpreserved
      and preserved beta-blockers on Chang conjunctival cells.
AB  - PURPOSE: Quaternary ammonium ions have been demonstrated to induce apoptosis
      correlated with superoxide anion production in vitro. The purpose of this study
      was to further investigate the mechanisms of benzalkonium chloride (BAC),
      unpreserved and preserved beta-blocker eye-drops-induced programmed cell death,
      with special attention to the roles of mitochondrial transmembrane potential and
      intracellular reduced glutathione. METHODS: Chang conjunctival cells were
      incubated with different concentrations of unpreserved or preserved timolol
      (0.1%, 0.25%, and 0.4%), or carteolol (1% and 2%), or BAC (0.0001% to 0.01%) for
      15 minutes, or for 15 minutes with a 24-hour recovery period in normal medium.
      Cellular viability (neutral red test), mitochondrial activity (rhodamine 123
      test), intracellular reduced glutathione (monochlorobimane test), DNA
      condensation (Hoechst 33342 test), and reactive oxygen species (ROS) production
      (dichlorofluorescein diacetate and hydroethidine tests) were evaluated using
      microplate cold-light cytofluorometry. RESULTS: A significant, concentration
      dependent decrease in cellular viability was found with preserved beta-blockers
      and with BAC alone, whereas unpreserved preparations did not show any toxicity.
      Only preserved beta-blockers induced chromatin condensation associated with an
      alteration of mitochondrial activity and a decrease of glutathione, suggesting an
      apoptotic phenomenon. BAC increased glutathione after 15 minutes, whereas a
      decrease was observed after a recovery period. ROS production was found with
      preserved formulations at significantly higher levels than those observed with
      unpreserved drugs. CONCLUSIONS: This in vitro study demonstrates that oxidative
      stress, evidenced by enhanced ROS production and mitochondrial injury rather than
      by cellular glutathione depletion, is a mechanism involved in apoptosis induced
      by preservative-containing eye-drops.

PMID- 11581194
TI  - Transforming growth factor-beta-stimulated connective tissue growth factor
      expression during corneal myofibroblast differentiation.
AB  - PURPOSE: Transforming growth factor beta1 (TGF-beta) stimulates the
      differentiation of myofibroblasts as indicated by the nascent expression of alpha
      smooth muscle (alpha-SM) actin protein and its organization into stress fibers.
      Downstream messengers of TGF-beta in the conversion from the fibroblast to the
      myofibroblast phenotype were investigated. Whether TGF-beta increases the
      transcription of a second growth factor, connective tissue growth factor 1
      (CTGF), which could mediate myofibroblast differentiation, was evaluated. CTGF, a
      newly identified growth factor, is highly expressed in dermal granulation tissue.
      METHODS: In this study, primary cultures of rabbit corneal fibroblasts were
      exposed to growth factors to investigate CTGF mRNA and protein expression during
      myofibroblast differentiation. Statistical analysis was used to evaluate the
      impact of growth factor treatment on myofibroblast differentiation. RESULTS: .
      TGF-beta treatment induced both CTGF mRNA and protein in rabbit corneal
      fibroblasts; in contrast, fibroblast growth factor-2 (FGF) and heparin led to a
      decrease in CTGF mRNA. Addition of recombinant CTGF to rabbit corneal fibroblast
      cultures did not significantly increase alpha-SM actin mRNA or protein nor did it
      appear to affect assembly of alpha-SM actin stress fibers. CONCLUSIONS: This is
      the first study to present evidence for the induction of CTGF by TGF-beta
      treatment of corneal fibroblasts. It is doubtful that CTGF is the TGF-beta
      mediator of the corneal fibroblast to myofibroblast transition because CTGF does
      not induce alpha-SM actin in subconfluent fibroblast cultures. CTGF may play a
      supporting role in myofibroblast differentiation.

PMID- 11581195
TI  - Long-term outcome and predictor variables in the treatment of acquired esotropia
      with botulinum toxin.
AB  - PURPOSE: To determine the long-term results of botulinum therapy in acquired
      esotropia and to identify predictors of a satisfactory outcome. METHODS: Sixty
      eight children (age range, 8-64 months) with acquired esotropia were enrolled in
      a prospective study. Botulinum toxin A was injected in the two medial recti.
      Motor and sensory statuses were evaluated at 1 and 2 weeks; 3, 6, and 12 months;
      and every year after the last injection. Univariate and multivariate logistic
      regression analyses were performed to relate motor and sensory outcome to
      variables recorded as potential predictors. RESULTS: After an average follow-up
      of 4.8 years since the last injection, motor success was obtained in 36 children
      with one injection (52.9%), increasing to 48 (70.6%) and 60 (88.2%) children
      after two and three injections, respectively. Forty-eight (70.6%) patients had at
      least peripheral fusion (category 1 binocularity) and 32 (47.1%) had stereoacuity
      of at least 400 seconds of arc (category 2 binocularity). Higher hypermetropia,
      less severe amblyopia, and a smaller angle of esotropia were the best predictors
      of motor success. Minimal amblyopia and favorable motor alignment were associated
      with better binocularity outcome. CONCLUSIONS: Botulinum is an effective long
      term treatment of acquired esotropia. It is especially useful in children with
      high hypermetropia, minimal amblyopia, and small esotropic deviation.

PMID- 11581196
TI  - A psychophysical measurement and analysis of motion perception in normal and
      binocularly deprived monkeys.
AB  - PURPOSE: To measure psychophysically the thresholds for motion detection in the
      nasal and temporal directions under monocular viewing conditions in monkeys
      reared under conditions of daily alternating monocular occlusion (AMO). The
      hypothesis was that motion perception would be asymmetric with more sensitivity
      for motion in the nasal direction. METHODS: Three monkeys subjected to AMO (AMO
      monkeys) and three normal monkeys were studied. All were trained with operant
      conditioning techniques to discriminate coherent from random motion in a random
      dot display. The percentage of dots in the display that moved either left or
      right was varied. Thresholds for motion detection of nasally directed and
      temporally directed stimuli were measured to determine whether the motion
      perception of AMO monkeys was asymmetric, as predicted. RESULTS: A two-factor
      analysis of variance revealed a statistically significant difference between
      treatment groups (normal versus AMO) and directions (nasal versus temporal) and a
      significant interaction. The interaction was due to a significant difference
      between nasal and temporal directions for the AMO group, but no significant
      difference for the normal group. Planned comparisons were performed based on each
      animal's best eye (eye most sensitive to nasal motion) and worst eye (eye least
      sensitive to temporal motion). No significant differences were found between the
      two groups in the best eyes' responses to the nasal direction, but the worst
      eyes' responses in the temporal direction were significantly poorer in the AMO
      group. A neural model that can account for these findings is based on a Hebbian
      teacher located in the nucleus of the optic tract that strengthens connections of
      a subpopulation of directionally selective cortical neurons. CONCLUSIONS: AMO
      rearing results in asymmetric motion perception. Thresholds for detecting nasally
      directed motion are normal, whereas thresholds for detecting temporally directed
      motion are deficient. These results demonstrate that motion-processing mechanisms
      in primates exhibit experience-dependent developmental neural plasticity. The
      locus of the neural plasticity could be a subpopulation of directionally
      selective neurons in the striate cortex (V1).

PMID- 11581197
TI  - Enhanced FGF-2 movement through human sclera after exposure to latanoprost.
AB  - PURPOSE: To determine whether exposure of sclera to latanoprost acid alters
      transscleral permeation by FGF-2. METHODS: Pieces of human sclera were isolated
      from donor eyes after death, placed in organ culture, and exposed to 50 to 200 nM
      latanoprost acid or vehicle for 3 days. Transscleral permeability was then
      assessed by placing each scleral piece into a Ussing apparatus and measuring the
      amount of FGF-2 that moves from the orbital side to the uveal side of the scleral
      piece. Transscleral permeation by 10-kDa tetramethylrhodamine-dextran also was
      determined, for comparison. RESULTS: Transscleral permeation by FGF-2 through
      sclera that had been incubated with vehicle was 1.53 +/- 0.86 x 10(-8) cm/sec.
      Transscleral permeation by 10-kDa tetramethylrhodamine-dextran was 1.04 +/- 0.39
      x 10(-6) cm/sec. FGF-2 permeation of sclera exposed to 50, 100, and 200 nM
      latanoprost acid was increased by an average of 48% +/- 62%, 100% +/- 108%, and
      108% +/- 79%, respectively, compared with sclera exposed to vehicle (n = 13; P <
      0.05). Scleral permeation by 10-kDa dextran after exposure to 50, 100, or 200 nM
      latanoprost acid was significantly increased by 42% +/- 36%, 59% +/- 51%, and 65%
      +/- 49%, respectively (n = 14; P < 0.05). The ratio of dextran to FGF-2
      permeation was approximately 90 and did not vary with 50, 100, or 200 nM
      latanoprost acid (P = 0.93, ANOVA). CONCLUSIONS: Exposure of sclera to
      latanoprost acid increases transscleral permeation by FGF-2 in human scleral
      organ cultures. Because this increase parallels the increased scleral
      permeability caused by dextran, it may reflect a general enhancement of
      permeability, a possibility that future in vivo studies should explore.

PMID- 11581198
TI  - Measurement of intraocular pressure in awake mice.
AB  - PURPOSE: To determine whether the Goldmann applanation tonometer can be modified
      to measure intraocular pressure (IOP) in the awake mouse. METHODS: Tonometers
      with reduction of the biprism angles in the applanating tips and in the weight
      applied by the instrument were tested in anesthetized mice in calibration
      experiments. Then a tonometer with the appropriate configuration of tip and
      weight was used in conscious, unsedated mice. RESULTS: Tonometry in mice required
      a biprism angle of 36 degrees and weight applied of 25 mg per scale division (2 g
      full scale). This tonometer was calibrated in mice against manometrically
      measured IOP and showed good agreement across the range of IOP tested (0-50 mm
      Hg). In conscious mice the measured mean Goldmann value was 13.7 +/- 3.2 mm Hg
      (mean +/- SD; 95% confidence interval, 13.1, 14.2 mm Hg). CONCLUSIONS: The
      Goldmann tonometer, the standard for measuring the IOP in the human eye, was
      modified to measure this fundamental physiologic parameter in the awake mouse.
      This measurement is required to confirm success in genetically engineering a
      model in the powerful mouse system, which mimics elevated IOP in humans. The
      model will open new avenues for studying the causes of the optic neuropathy of
      glaucoma, the regulation of IOP, and new therapeutic approaches to prevent the
      irreversible loss of vision from this disease.

PMID- 11581199
TI  - Inhibition of leukocyte sticking and infiltration, but not rolling, by antibodies
      to ICAM-1 and LFA-1 in murine endotoxin-induced uveitis.
AB  - PURPOSE: Cell-adhesion molecules are critical elements in intravascular rolling
      and sticking of leukocytes during acute inflammation. In this process, selectins
      are thought to be involved in initial adhesion and rolling, and integrin-Ig
      superfamily interactions are believed primarily to mediate stronger adhesion and
      transendothelial migration. This study clarifies the role of two adhesion
      molecules, intercellular adhesion molecule (ICAM)-1 and leukocyte functional
      antigen (LFA)-1, in endotoxin-induced uveitis (EIU). METHODS: Intravital
      microscopy was used to record the movement and location of leukocytes in the
      irises of mice with uveitis induced by intravitreal injection of 250 ng
      Escherichia coli endotoxin. Each mouse concurrently received an intraperitoneal
      injection of monoclonal neutralizing antibodies for ICAM-1, LFA-1, or both or
      control irrelevant antibodies. RESULTS: Mice treated with endotoxin and control
      antibodies had an inflammatory response that was clearly present at the 6- and 24
      hour time points and was mostly resolved by 48 hours. Mice that received anti
      ICAM-1 or anti-LFA-1 had significantly fewer cells infiltrating their irises at 6
      and 24 hours. Detailed analysis of the 6-hour time point recordings revealed that
      neither anti-ICAM-1 nor anti-LFA-1 significantly reduced the number of leukocytes
      rolling on venule endothelial surfaces, but the treatments reduced the number of
      firmly adherent cells. CONCLUSIONS: These data confirm previous reports that ICAM
      1 and LFA-1 are important mediators of EIU. The dynamic in vivo images clearly
      support the hypothesis that integrin-mediated cell adhesion is more critical for
      the firm adhesion of sticking cells than for leukocyte rolling.

PMID- 11581200
TI  - Cytokines in autoimmune lacrimal gland disease in MRL/MpJ mice.
AB  - PURPOSE: MRL/MpJ-+/+ (MRL/+) and MRL/MpJ-lpr/lpr (MRL/lpr) mice show spontaneous
      development of a T-cell-driven lacrimal gland inflammation that is a model for
      Sjogren syndrome. The lacrimal gland lesions in these mice were evaluated by
      quantitative RT-PCR for selected cytokine mRNA for the relative contributions of
      T-helper (Th)1 versus Th2 immune responses and by RT-PCR and immunohistochemistry
      for the contribution of the interleukin (IL)-2/IL-2 receptor (IL-2R) autocrine
      pathway. METHODS: RNA was isolated from lacrimal glands of MRL/+ mice ages 1 to 9
      months and from MRL/lpr mice ages 1 through 5 months, and competitive RT-PCR was
      used to quantify mRNA for the cytokines IL-2, -4, -10, and -12 and interferon
      (IFN)-gamma. Frozen sections of lacrimal glands from MRL/+ and MRL/lpr mice ages
      2 through 5 months were stained for the IL-2R. RESULTS: IL-2 and -12 mRNA
      transcripts were below the limit of detection (<10(-3) fg/pg hypoxanthine
      phosphoribosyl transferase gene; HPRT) in both MRL/+ and MRL/lpr mice of all
      ages. When detectable, IFN-gamma transcripts were present in low amounts and were
      below the limit of detection in most samples. IL-4 transcripts were present in
      100- to 1000-fold greater amounts than IFN-gamma transcripts. IL-10 transcripts
      were detectable in both MRL/+ and MRL/lpr mice. IL-2R typically was detected on
      less than 10% of lymphocytes infiltrating lacrimal gland lesions in both
      substrains. CONCLUSIONS: On the basis of RT-PCR for cytokine mRNA, autoimmune
      lacrimal gland lesions in MRL/+ and MRL/lpr mice appear to be largely Th2
      mediated. There does not appear to be a direct role for the IL-2/IL-2R autocrine
      pathway within the microenvironment of the lacrimal gland.

PMID- 11581201
TI  - Detection of varicella zoster virus DNA in some patients with giant cell
      arteritis.
AB  - PURPOSE: The purpose of this study was to determine whether an association exists
      between giant cell arteritis (GCA) and the presence of varicella-zoster virus
      (VZV), by using histologic, molecular, immunohistochemical, and ultrastructural
      analyses of temporal artery biopsy specimens. METHODS: In a randomized masked
      study, 64 temporal artery biopsy specimens were analyzed by PCR for VZV DNA. The
      samples included 35 specimens histologically positive and 29 specimens
      histologically negative for GCA. Immunohistochemical staining for VZV viral
      antigen IE-63 was performed on seven of the specimens positive for GCA and five
      negative specimens. Transmission electron microscopy (TEM) was performed on five
      of the specimens positive for GCA. RESULTS: PCR was positive for VZV DNA in 9
      (26%) temporal arteries tested that showed histologic evidence of GCA. The
      remaining 26 histologically positive temporal arteries and all 29 histologically
      negative arteries tested gave negative PCR results for VZV DNA. Statistical
      analysis (z-test) comparing the association of VZV DNA between the specimens that
      were positive and negative for GCA showed a significant difference (P = 0.010).
      Immunohistochemical studies were positive in several biopsy specimens within
      adventitial histiocytes-macrophages, but these results did not correlate with
      either the presence or absence of VZV DNA or with the histologic evidence of GCA.
      No viral particles were observed by TEM. CONCLUSIONS: This study showed a
      significant association of VZV DNA to temporal artery biopsy samples positive for
      GCA compared with the negative specimens. The results support the hypothesis that
      VZV may play a role in the pathogenesis of some cases of GCA. However, PCR,
      immunohistochemical, and electron microscopic findings suggest the virus is
      present at extremely low quantities, is abortively replicating, or is latent.

PMID- 11581202
TI  - Molecular screening of donor corneas for fungi before excision.
AB  - PURPOSE: To develop panfungal and Candida albicans species-specific polymerase
      chain reaction (PCR) assays to screen donor eyes for fungal contamination before
      corneal excision. METHODS: PCR primers were designed for either the broad
      spectrum detection of fungal DNA or the specific detection of C. albicans DNA.
      Their sequences were based on rDNA regions highly conserved among and specific to
      fungi and C. albicans, respectively. PCR conditions with the two primer sets were
      optimized and tested for sensitivity using purified C. albicans genomic DNA and a
      plasmid containing the relevant region of C. albicans DNA. The specificity of the
      primer sets was established using higher eukaryotic, fungal, prokaryotic, and
      viral DNAs as PCR templates. Donor eye swab specimens were collected before
      corneal excision. DNA was extracted from the specimens and tested by both PCR
      assays. RESULTS: The lower limit of detection for both primer sets was
      consistently 10(3) genome equivalents, when using genomic DNA as a template and
      10(2) copies of plasmid. The fungal PCR assay amplified DNA from all fungal
      species tested but did not amplify any of the selected mammalian, bacterial, or
      viral DNA. The C. albicans PCR detected the C. albicans DNA but was negative for
      all other DNA substrates, including the other fungal templates. Thirty-five
      percent of the donor eye samples tested were positive for fungus, and 19% were
      positive for C. albicans DNA. CONCLUSIONS: The PCR assays allowed the rapid
      screening of DNA extracted from specimens collected from corneal donors for
      potential fungal contamination. The assay was highly sensitive and specific for
      screening corneal surfaces. The results suggest that approximately one-third of
      donor eyes tested harbor fungi on the ocular surface.

PMID- 11581203
TI  - Relationship between aqueous humor protein level and outflow facility in patients
      with uveitis.
AB  - PURPOSE: To determine whether there is a relationship between the aqueous humor
      protein level and outflow facility in patients with uveitis. METHODS: Aqueous
      humor protein levels were determined by laser flare photometry, and outflow
      facility was determined by Schiotz tonography. RESULTS: Thirty patients with
      uveitis and 10 control subjects were studied. Outflow facility was lower in
      patients with uveitis (0.21 +/- 0.12 microl/min x mm Hg) than in control subjects
      (0.33 +/- 0.05 microl/min x mm Hg, P < 0.001). Patients with uveitis and laser
      flare photometry results (flare) more than 20 photon units/msec (n = 21) had a
      lower outflow facility (0.17 +/- 0.07 microl/min x mm Hg) than patients with
      uveitis and flare less than 20 photon units/msec (n = 9, 0.32 +/- 0.14 microl/min
      x mm Hg, P = 0.004). Furthermore, no difference was identified between outflow
      facility in patients with active uveitis (those who had anterior chamber cells)
      and flare less than 20 photon units/msec and outflow in control subjects. In
      patients with uveitis, there was a linear correlation between flare and outflow
      facility (r = -0.50, P = 0.005). There was no relationship between flare
      measurements and either intraocular pressure or aqueous humor cell levels when
      scored with a clinical, semiquantitative system. CONCLUSIONS: Outflow facility is
      significantly reduced in patients with uveitis who have high aqueous humor
      protein levels. Outflow facility appears to be normal in patients with active
      uveitis whose flare levels are low, and therefore the association between flare
      and outflow facility does not appear to be an indirect reflection of elevated
      anterior chamber cells. It is possible that elevated aqueous humor protein levels
      contribute to the development of uveitic glaucoma in some individuals by
      decreasing aqueous humor outflow facility, although a causal relationship cannot
      be established on the basis of this study.

PMID- 11581205
TI  - Action spectrum and recovery for in vitro UV-induced cataract using whole lenses.
AB  - PURPOSE: To establish the in vitro action spectrum for acute UV cataractogenesis
      using whole cultured lenses. The recovery pattern of the induced cataract was
      also investigated. METHODS: Aseptically dissected porcine lenses were cultured in
      glass chambers. At 1 week, lenses were exposed to a predetermined UV energy
      (J/cm(2)) at specific wavebands ranging from 270 to 370 nm at 5- and 10-nm
      intervals. The UV energy was generated by a PRA integrated arc lamp system using
      a water-cooled 1000 W, high-pressure xenon lamp. The lamp output was limited
      using a deionized water filter, a monochromator, and secondary optics. An
      electronic shutter was used to control the exposure time. The median effective
      dose, ED(50) (i.e., UV energy threshold) for each waveband was statistically
      determined using probit analysis. Irradiated spots (3.06 mm(2)) on the lenses
      were monitored every 6 to 12 hours up to 48 hours postirradiation for any UV
      induced opacity with a dissecting microscope and photomicrography. The ED(50)s
      were plotted against wavelengths to obtain the action spectrum. RESULTS: The
      threshold values for 270, 300, and 365 nm were 0.057, 0.069, and 137.19 J/cm(2),
      respectively. Permanent UV-induced cataract was obtained at twice the threshold
      values for UVB and UVA. CONCLUSIONS: An action spectrum for in vitro UV-induced
      cataract using whole cultured lens is established. These data are comparable to
      published in vitro (with isolated lens epithelial cells) and in vivo action
      spectra. The recovery pattern appears to be similar to the in vivo situation.

PMID- 11581204
TI  - Retinal dysfunction in cancer-associated retinopathy is improved by Ca(2+)
      antagonist administration and dark adaptation.
AB  - PURPOSE: It was recently found that recoverin acts as an autoantigen recognized
      by sera of patients with cancer-associated retinopathy (CAR), and that CAR-like
      retinal dysfunction is produced by intravitreous administration of anti-recoverin
      antibody in Lewis rat eyes. To examine the pathologic molecular mechanism of CAR,
      and to elucidate an effective therapy for CAR, the function and morphology of CAR
      were compared with those of phototoxic retinal damage, another form of
      photoreceptor dysfunction, and the effect of nilvadipine, a Ca(2+) antagonist, on
      the retinal degenerations was studied, using these models. METHODS: Under
      different illumination conditions and/or medication with nilvadipine, the
      functional and morphologic properties of the retinas were evaluated after
      intravitreous injection of anti-recoverin antibody into Lewis rat eyes (six rats,
      12 eyes in each experimental condition), using electroretinogram (ERG), rhodopsin
      phosphorylation, and light microscopy. RESULTS: Anti-recoverin antibody
      administered into the vitreous of Lewis rat eyes induced a significant decrease
      and increase of ERG responses and rhodopsin phosphorylation levels, respectively,
      under cyclic or continuous light. Similar changes were observed in eyes of rats
      bred under continuous illumination that did not receive anti-recoverin
      antibodies. However, anti-recoverin antibody-induced retinal dysfunctions were
      not observed in rat eyes under dark conditions. Administration of nilvadipine, a
      Ca(2+) antagonist, to the anti-recoverin antibody-treated rats and rats with
      phototoxic retinal dysfunction caused significant improvement of the
      deterioration of ERG and normalization of rhodopsin phosphorylation. CONCLUSIONS:
      The present data indicate that anti-recoverin antibody-induced retinal
      dysfunction was functionally similar to phototoxic retinal dysfunction and was
      markedly suppressed under dark conditions or by systemic administration of a
      Ca(2+) antagonist.

PMID- 11581206
TI  - Analysis of expression patterns of protein phosphatase-1 and phosphatase-2A in
      rat and bovine lenses.
AB  - PURPOSE: The reversible phosphorylation and dephosphorylation at the serine and
      threonine residues on proteins play distinct roles in regulating multiple
      cellular activities. Whereas the protein serine-threonine kinases have been well
      studied in the lens system, very little is known about the expression and
      function of the serine-threonine phosphatases. The present article reports the
      expression patterns of protein phosphatase (PP)-1 and -2A in adult rat and bovine
      lenses. METHODS: Total RNAs and proteins were extracted from the epithelial and
      fiber cells of rat and bovine lenses. RT-PCR and Northern blot analysis were used
      to detect the mRNA expression levels in the epithelial cells and different
      fractions of fiber cells of these two types of lenses. Western blot was used to
      examine the protein expression levels in these different samples. An enzymatic
      assay was used to detect the activity distribution of PP-1 and -2A in these
      samples. RESULTS: The mRNAs for the PP-1 catalytic subunit (PP-1cs) and PP-2A
      catalytic subunit (PP-2Acs) were expressed in both epithelial and fiber cells of
      rat and bovine lenses. A detailed examination of the expression patterns of the
      two mRNAs in different fractions of fiber cells revealed that the cortical fiber
      cells (F1) contain the highest level of PP-1cs and -2Acs mRNAs (similar to those
      in the epithelial cells) among different fractions of fiber cells. The levels of
      the two mRNAs were sequentially decreased in the next layers of fiber cells (F2
      and F3) and became barely detectable in the inner layers of fiber cells (F4 and
      N). In contrast to the mRNA expression patterns, the PP-1cs protein was mainly
      found in the epithelial cells. Among different layers of fiber cells, only
      cortical (F1) fiber cells contained detectable level of PP-1cs protein (bovine
      lenses contained a relatively higher level of PP-1cs than rat lenses in this
      region). In the remaining fiber cells, the PP-1cs protein was hardly detectable
      in rat lenses and slightly detectable in bovine lenses. The PP-2Acs protein was
      detectable only in the lens epithelial cells. Enzymatic assays revealed that the
      distribution patterns of PP-1 and -2A activities were similar to those of PP-1cs
      and -2Acs proteins. Furthermore, PP-1 activity was approximately four to five
      times higher than PP-2A activity in the lens epithelial cells. CONCLUSIONS: This
      study demonstrates that active PP-1 and -2A are mainly distributed in the lens
      epithelial cells, with PP-1 as a major phosphatase. The mRNAs and proteins for PP
      1cs and -2Acs are differentially expressed in the epithelial and fiber cells of
      rat and bovine lenses.

PMID- 11581207
TI  - Lovastatin-induced cytoskeletal reorganization in lens epithelial cells: role of
      Rho GTPases.
AB  - PURPOSE: To understand the involvement of isoprenylated small guanosine
      triphosphatases (GTPases) in lovastatin-induced cataractogenesis, Rho- and Rac
      mediated cell adhesion and actin cytoskeletal reorganization were investigated in
      lovastatin-treated lens epithelial cells. METHODS: The effects of lovastatin on F
      actin reorganization (phalloidin staining), focal adhesion formation (paxillin or
      vinculin), cell-cell adhesions (cadherin and beta-catenin), and protein tyrosine
      phosphorylation were evaluated in human and porcine lens epithelial cells by
      immunocytochemical staining with specific antibodies. To explore the involvement
      of the Rho and Rac GTPases in lovastatin-mediated effects, changes in
      distribution of Rho and Rac GTPases were analyzed by Western blot analysis, and
      the effects of C3-exoenzyme on lovastatin-induced cytoskeletal changes were
      evaluated by immunocytochemical analysis. RESULTS: Lovastatin induced drastic
      changes in cell shape in both human and porcine lens epithelial cells, including
      a profound loss of actin stress fibers, focal adhesions, protein phosphotyrosine,
      and cell-cell adhesions. Lovastatin treatment also led to the accumulation of
      nonisoprenylated Rho and Rac GTPases in cytosolic fraction. Supplementation of
      culture media with geranylgeranyl pyrophosphate dramatically reversed the
      lovastatin-induced morphologic and cytoskeletal changes, whereas farnesyl
      pyrophosphate was ineffective. Treatment of cells with C3-exoenzyme (a Rho GTPase
      specific inhibitor), however, abolished the geranylgeranyl-supplementation
      induced recovery from the morphologic and cytoskeletal effects of lovastatin.
      CONCLUSIONS: This study demonstrates that inhibition of protein prenylation by
      lovastatin leads to disruption of actin cytoskeletal organization, and to loss of
      integrin-mediated focal adhesions and cadherin-mediated cell-cell adhesions in
      lens epithelial cells. Based on isoprenoid supplementation studies, it could be
      concluded that impairment of geranylgeranylated Rho and Rac GTPase function is
      most likely responsible for lovastatin-induced cytoskeletal changes in lens
      epithelial cells.

PMID- 11581208
TI  - Expression of cyclooxygenase-1 and -2 in normal and glaucomatous human eyes.
AB  - PURPOSE: Primary open-angle glaucoma (POAG) is the predominant form of chronic
      glaucoma, but the underlying pathologic mechanisms are largely unknown. Because
      prostaglandins (PGs) have been introduced into POAG treatment with remarkable
      success, this study was undertaken to investigate whether a change in the
      expression of the PG-synthesizing enzymes cyclooxygenase (COX)-1 and -2 might be
      involved in the pathogenesis of POAG. METHODS: Expression of COX-1 and -2 was
      assessed by confocal laser microscopy, immunohistochemistry, Western blot
      analysis, and real-time RT-PCR in human eyes with different forms of glaucoma
      (primary open-angle, angle-closure, congenital juvenile, and steroid-induced), as
      well as in age-matched control eyes. Additionally, PGE2 was measured in aqueous
      humor by means of an enzyme-linked immunoassay as a product of COX activity.
      RESULTS: In normal eyes, ocular COX-1 and -2 expression were largely confined to
      the nonpigmented secretory epithelium of the ciliary body. By
      immunohistochemistry and real-time RT-PCR, COX-2 expression was completely lost
      in the nonpigmented secretory epithelium of the ciliary body of eyes with end
      stage POAG, whereas COX-1 expression was unchanged. By immunohistochemistry, in
      the ciliary bodies of eyes in five patients with diagnosis of early POAG, eyes in
      two had complete loss of COX-2 expression and in three showed only a few
      remaining scattered COX-2-expressing cells. COX-2 expression in the ciliary body
      was also lost in patients with steroid-induced glaucoma and was reduced in
      patients receiving topical steroid treatment. Eyes of patients with either
      congenital juvenile or angle-closure glaucoma showed COX-2 expression
      indistinguishable from control eyes. Aqueous humor of eyes with POAG contained
      significantly less PGE2 than control eyes. CONCLUSIONS: Both cyclooxygenase
      isoforms are constitutively expressed in the normal human eye. Specific loss of
      COX-2 expression in the nonpigmented secretory epithelium of the ciliary body
      appears to be linked to the occurrence of POAG and steroid-induced glaucoma.

PMID- 11581209
TI  - Carbachol and nitric oxide inhibition of Na,K-ATPase activity in bovine ciliary
      processes.
AB  - PURPOSE: Nitric oxide (NO) donors and cholinergic agents decrease intraocular
      pressure, in part because they induce a decrease in aqueous humor production.
      Because Na,K-adenosine triphosphatase (ATPase) is involved in aqueous humor
      formation, this study was conducted to investigate the hypothesis that NO and
      cholinomimetics regulate its activity in bovine ciliary processes. METHODS:
      Bovine tissue slices were incubated with agonists and antagonists in a
      physiological buffer in vitro. Na,K-ATPase activity was determined by assaying
      hydrolysis of adenosine triphosphate (ATP) in suspended permeabilized tissue
      slices. RESULTS: Carbachol-induced inhibition of Na,K-ATPase activity correlated
      with increases in cGMP. This inhibition was abolished by the muscarinic blocker
      atropine, the NO inhibitor N(w)-nitro-L-arginine (L-NAME) and the soluble
      guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ).
      Sodium nitroprusside (SNP) mimicked the actions of carbachol. The SNP-induced
      decrease in Na,K-ATPase activity correlated with an increase in cGMP and was also
      abolished by ODQ. Both 8-bromo (Br)-cGMP and okadaic acid also inhibited Na,K
      ATPase activity. CONCLUSIONS: Carbachol-induced inhibition of Na,K-ATPase
      activity involves muscarinic receptor activation. That SNP mimics and L-NAME
      reverses carbachol's effect on Na,K-ATPase activity suggests that the actions of
      carbachol are mediated by NO. Carbachol's and SNP's effects on Na,K-ATPase
      activity involved soluble guanylate cyclase and cGMP. Inhibition of Na,K-ATPase
      activity by 8-Br-cGMP and okadaic acid indicates that protein phosphorylation
      events may mediate SNP-induced inhibition of Na,K-ATPase activity.

PMID- 11581210
TI  - Adult rabbit retinal transplants.
AB  - PURPOSE: To study the survival of adult retinal grafts prepared in a
      physiologically optimized way. METHODS: Twenty-three rabbits received an adult
      full-thickness rabbit retinal transplant positioned under the host retina, using
      a vitrectomy technique. The transplants were prepared using a procedure based on
      a previously described in vitro model used for physiological experiments on the
      adult retina. Five rabbits received a fragmented graft. All grafts were
      prelabeled with 4',6-diaminidin-2-phenylindoldihydrochloride (DAPI) to allow
      identification. The eyes were examined by light and fluorescence microscopy 6 to
      174 days after surgery. To assess the amount of cell death in the graft before
      actual transplantation, in vitro experiments were performed. The extent of cell
      death in retinas prepared by the optimized protocol was examined and compared
      with a simpler preparation previously used successfully for embryonic grafts. The
      amount of cell death in the in vitro experiments was evaluated using a
      fluorescent green nucleic acid stain that penetrates dying cells. RESULTS: In 21
      of the 23 animals that received full-thickness grafts prepared in an optimized
      way, the transplant survived. Sixteen grafts, including all four with a 174-day
      survival time, displayed normal morphology, with all retinal layers preserved.
      The fragmented grafts survived poorly. The in vitro experiments showed minimal
      cell death in retinas prepared according to the optimized protocol, whereas
      control retinas displayed extensive cell death after 5 hours. CONCLUSIONS: The
      results showed that it is possible to transplant adult retina in the rabbit and
      that the grafts survive well if they are prepared under physiologically optimized
      conditions and the integrity of the grafted tissue is kept intact.

PMID- 11581211
TI  - PDT to monkey CNV with ATX-S10(Na): inappropriateness of early laser irradiation
      for selective occlusion.
AB  - PURPOSE: There is controversy about which mode of laser irradiation, early
      irradiation with low-dose photosensitizer or late irradiation with high-dose,
      benefits the selective occlusion of choroidal neovascularization (CNV) in
      photodynamic therapy (PDT). In this study, using an amphiphilic photosensitizer,
      13,17-bis (1-carboxypropionyl) carbamoylethyl-8-etheny-2-hydroxy-3
      hydroxyiminoethylidene-2,7,12,18-tetraethyl porphyrin sodium (ATX-S10(Na);
      Photochemical Inc., Okayama, Japan), photodynamic and adverse effects of early
      irradiation on CNV-bearing monkey eyes were investigated. METHODS: Experimentally
      induced CNV lesions and normal retina were irradiated with a diode laser (670-nm
      wavelength) at a dose of 1 to 90 J/cm(2) at 1 to 19 minutes after intravenous
      injection of 2 mg/kg body weight of ATX-S10(Na). Vascular occlusion and CNV
      recurrence were evaluated by fluorescein and indocyanine green angiography and
      histologic analysis, until 4 weeks after irradiation. RESULTS: Of 45 different
      conditions, 23 did not induce CNV closure, 20 provided both CNV occlusion and
      retinal vessel damage, and 2 achieved selective CNV occlusion without retinal
      vascular injury. Recurrence of CNV was induced in 19 of 22 CNV-occluding
      conditions. ATX-S10(Na) angiography showed that dyes were similarly distributed
      between normal vessels and CNV at early time periods after injection, whereas
      they were preferentially accumulated in CNV after 30 minutes. CONCLUSIONS: In PDT
      with ATX-S10(Na), irradiation within 20 minutes of dye injection failed to induce
      selective CNV occlusion, probably because there is no significant difference in
      the biodistribution of dye between CNV and retinal vessels. It also caused
      frequent CNV recurrence after extensive inflammation in the irradiated retina.

PMID- 11581212
TI  - Antiviral activity and ocular kinetics of antisense oligonucleotides designed to
      inhibit CMV replication.
AB  - PURPOSE: To compare the antiviral activity and ocular distribution of first- and
      second-generation antisense oligonucleotides intended for the treatment of
      cytomegalovirus (CMV) retinitis. METHODS: The antiviral activity of ISIS 13312
      and ISIS 2922 (Isis Pharmaceuticals, Inc., Carlsbad, CA) against 10 clinical CMV
      isolates was compared with a plaque-reduction assay. The ocular pharmacokinetics
      were compared after intravitreal injection in rabbits (36-90 microg) and monkeys
      (125-500 microg). Vitreous and/or retina were collected after single and multiple
      injections to characterize ocular distribution, clearance, and accumulation.
      Oligonucleotide concentrations were measured by capillary gel electrophoresis and
      immunohistochemical techniques. RESULTS: ISIS 13312 and ISIS 2922 demonstrated
      comparable antiviral activity that was consistent among the 10 clinical isolates
      examined (50% inhibitory concentration [IC(50)], <1 microM). Activity was
      independent of the resistance of CMV isolates to DNA polymerase inhibitors. After
      intravitreal injection, the kinetics of ISIS 2922 and ISIS 13312 were
      characterized by clearance from vitreous and distribution to the retina; however,
      ISIS 2922 was cleared more quickly from the retina than ISIS 13312. The half-life
      of ISIS 13312 in the monkey retina was approximately 2 months. Retinal
      concentrations of ISIS 13312 were dose dependent, with approximately a twofold
      increase in concentration after once-monthly doses compared with single-dose
      concentrations. Immunohistochemical analysis indicated that both oligonucleotides
      were efficiently distributed to numerous ocular tissues, including retina,
      ciliary body, and optic nerve. CONCLUSIONS: ISIS 13312 possesses antiviral
      activity and pharmacokinetic properties that favor its use as a therapeutic agent
      in treatment of CMV retinitis. The half-life of ISIS 13312 in retina is longer
      than that of ISIS 2922, potentially allowing for less frequent administration.

PMID- 11581213
TI  - A novel gene for autosomal dominant Stargardt-like macular dystrophy with
      homology to the SUR4 protein family.
AB  - PURPOSE: To describe a novel gene causing a Stargardt-like phenotype in a family
      with dominant macular dystrophy and the exclusion of all known genes within the
      disease locus. METHODS: Meiotic breakpoint mapping in a family of 2314
      individuals enabled refinement of the location of the disease gene. The genomic
      organization and expression profile of known and putative genes within the
      critical region were determined using bioinformatics, cDNA cloning, and RT-PCR.
      The coding sequence of genes expressed within the retina was scanned for
      mutations, by using DNA sequencing. RESULTS: The disease-causing gene (STGD3) was
      further localized to 562 kb on chromosome 6 between D6S460 and a new polymorphic
      marker centromeric to D6S1707. Of the four genes identified within this region,
      all were expressed in the retina or retinal pigment epithelium. The only coding
      DNA sequence variant identified in these four genes was a 5-bp deletion in exon 6
      of ELOVL4. The deletion is predicted to lead to a truncated protein with a net
      loss of 44 amino acids, including a dilysine endoplasmic reticulum retention
      motif. The ELOVL4 gene is the fourth known example of a predicted human protein
      with homology to mammalian and yeast enzymes involved in the membrane-bound fatty
      acid chain elongation system. The genomic organization of ELOVL4 and primer sets
      for exon amplification are presented. CONCLUSIONS: ELOVL4 causes macular
      dystrophy in this large family distributed throughout North America and
      implicates fatty acid biosynthesis in the pathogenesis of macular degeneration.
      The PCR-based assay for the 5-bp deletion will facilitate more accurate genetic
      counseling and identification of other branches of the family.

PMID- 11581214
TI  - Monoclonal antibody-mediated drug targeting to choroidal neovascularization in
      the rat.
AB  - PURPOSE: Active drug targeting mediated by monoclonal antibodies (mAbs) of
      vascular endothelial cells in tumors is a new concept in cancer therapy. Integrin
      alphavbeta3 has been reported to be strongly expressed in vascular endothelial
      cells of surgically excised choroidal neovascular membranes and is thought to be
      a potential antigen for mAb-mediated drug targeting of choroidal
      neovascularization (CNV). The objective of this study was to evaluate the
      efficacy of drug targeting mediated by anti-integrin alphavbeta3 mAbs in a laser
      induced CNV rat model. METHODS: The mitomycin C (MMC)-dextran (MMCD) conjugate
      was synthesized with a carbodiimide-catalyzed reaction. The mAb was conjugated
      with MMCD (MMCD-mAb). To evaluate the feasibility of mAb-mediated drug targeting
      in vitro, we investigated the effect of the immunoconjugates involving dextran
      binding MMC on the proliferation of human umbilical vein endothelial cells
      (HUVECs). CNV was induced by laser photocoagulation in male Brown Norway rats.
      Immunolocalization of integrin alphavbeta3 in CNV lesions was assessed
      immunohistochemically with the anti-von Willebrand factor antibody as an
      endothelial cell marker. Intravenous administration of saline (n = 7), 1 mg/day
      mAb (n = 7), 100 microg/kg per day free MMC (n = 7), MMCD with irrelevant Ab (n =
      7), unconjugated MMCD with unconjugated mAb (MMCD+mAb; n = 7), or MMCD with mAb
      (MMCD-mAb; n = 8) containing an equal amount of free MMC, was performed daily for
      3 days from day 14 after CNV induction. CNV was assessed by fluorescein
      angiography 2 weeks after treatment. Fluorescein leakage was scored on a four
      grade scale. The animals were killed 2 weeks after treatment, and the lesions
      were evaluated histologically. RESULTS: The inhibition of immunoconjugates on the
      proliferation of HUVECs was enhanced specifically by the mediatory effect of the
      mAb. Endothelial cells demonstrated strong immunoreactivity of integrin
      alphavbeta3 in the CNV. In the vehicle-treated group, fluorescein leakage equal
      to that before treatment was observed 2 weeks after treatment, with an average
      score of 2.00 +/- 0.17 (mean +/- SEM). MMCD-mAb significantly inhibited the
      development of CNV in rats (P < 0.01). Moreover, the thickness of the lesions was
      significantly reduced in the MMCD-mAb-treated group (P < 0.01). CONCLUSIONS:
      Immunoconjugates effectively inhibited progression of CNV in this model. The
      results suggest that mAb-mediated drug targeting may be beneficial in the
      treatment of CNV.

PMID- 11581215
TI  - Pulsed electron avalanche knife (PEAK) for intraocular surgery.
AB  - PURPOSE: To develop a better and more economical instrument for precise,
      tractionless, "cold" cutting during intraocular surgery. The use of highly
      localized electric fields rather than laser light as the means of tissue
      dissection was investigated. METHODS: A high electric field at the tip of a fine
      wire can, like lasers, initiate plasma formation. Micrometer-length plasma
      streamers are generated when an insulated 25 micron (microm) wire, exposed to
      physiological medium at one end, is subjected to nanosecond electrical pulses
      between 1 and 8 kV in magnitude. The explosive evaporation of water in the
      vicinity of these streamers cuts soft tissue without heat deposition into
      surrounding material (cold cutting). Streamers of plasma and the dynamics of
      water evaporation were imaged using an inverted microscope and fast flash
      photography. Cutting effectiveness was evaluated on both polyacrylamide gels, on
      different tissues from excised bovine eyes, and in vivo on rabbit retina.
      Standard histology techniques were used to examine the tissue. RESULTS: Electric
      pulses with energies between 150 and 670 microJ produced plasma streamers in
      saline between 10 and 200 microm in length. Application of electric discharges to
      dense (10%) polyacrylamide gels resulted in fracturing of the gel without
      ejection of bulk material. In both dense and softer (6%) gels, layer by layer
      shaving was possible with pulse energy rather than number of pulses as the
      determinant of ultimate cutting depth. The instrument made precise partial or
      full-thickness cuts of retina, iris, lens, and lens capsule without any evidence
      of thermal damage. Because different tissues require distinct energies for
      dissection, tissue-selective cutting on complex structures can be performed if
      the appropriate pulse energies are used; for example, retina can be dissected
      without damage to the major retinal vessels. CONCLUSIONS: This instrument, called
      the Pulsed Electron Avalanche Knife (PEAK), can quickly and precisely cut
      intraocular tissues without traction. The small delivery probe and modest cost
      make it promising for many ophthalmic applications, including retinal, cataract,
      and glaucoma surgery. In addition, the instrument may be useful in nonophthalmic
      procedures such as intravascular surgery and neurosurgery.

PMID- 11581216
TI  - Abnormal centrifugal axons in streptozotocin-diabetic rat retinas.
AB  - PURPOSE: To characterize the effects of diabetes on the expression of histidine
      decarboxylase mRNA and on the morphology of the histaminergic centrifugal axons
      in the rat retina. METHODS: Rats were made diabetic by streptozotocin. After 3
      months, retinal histidine decarboxylase expression was analyzed by in situ
      hybridization in radial sections. Flatmount retinas from a second group of rats
      were labeled with an antiserum to histamine or an antibody to phosphorylated
      neurofilament protein. RESULTS: Histidine decarboxylase mRNA was expressed in
      cells in the inner and outer nuclear layers of diabetic retinas, but not in
      normal retinas. However, immunoreactive (IR) histamine was not localized to
      perikarya in either the normal or the diabetic retinas. Instead, a population of
      centrifugal axons was labeled. These axons emerged from the optic disc and had
      varicose terminal branches in the inner plexiform layer (IPL) of the peripheral
      retina. Some branches ended on large retinal blood vessels and others in dense
      clusters in the IPL. In rats with streptozotocin-induced diabetes, the
      centrifugal axon terminals developed many large swellings that contained
      neurofilament immunoreactivity; these swellings were rare in normal retinas.
      CONCLUSIONS: Diabetes perturbs the retinal histaminergic system, causing
      increases in histidine decarboxylase mRNA expression in neurons or glia and
      abnormal focal swellings on the centrifugal axons.

PMID- 11581217
TI  - Effects of retinal glial cells on isolated rat retinal ganglion cells.
AB  - PURPOSE: The effect of retinal glial cells on retinal ganglion cell (RGC)
      survival was investigated in cocultures of pure, isolated retinal glial cells
      with pure, isolated RGCs. METHODS: RGCs from 2-day-old rats were cocultured for
      48 hours, avoiding direct contact between cell types, with either nonconfluent
      retinal glial cells from 3-day-old rats or confluent retinal glial cells from 3
      day-old, 12-day-old, or 1-year-old rats. Survival of RGCs was evaluated by flow
      cytometry. Amino acids were determined in culture medium. The effects of
      glutamate antagonists, 6-cyano-7-nitroquinoxaline-2,3-dione and MK801, a nitric
      oxide (NO) scavenger, 2-(4-carboxyphenyl)-4,4,5,5tetramethylimidazoline-1-oxyl-3
      oxide potassium salt (c-PTIO), and an NO synthase inhibitor, N(G)-nitro-L
      arginine methyl ester (L-NAME), were examined. RESULTS: Nonconfluent retinal
      glial cells significantly reduced the survival of small and large RGCs, but
      confluent retinal glial cells reduced the survival of only small RGCs, regardless
      of the rat's age at the time of retinal glial cell harvesting. Profiles of some
      amino acids significantly varied, depending on the culture condition. Cocultures
      of RGCs with nonconfluent retinal glial cells released significantly more
      glutamate into the medium than cocultures of RGCs with confluent retinal glial
      cells or RGCs in pure culture. The glutamate antagonists improved the survival of
      RGCs cocultured with nonconfluent retinal glial cells, especially when the two
      were administered in combination, and in the case of large RGCs. c-PTIO and L
      NAME, also improved the survival of RGCs cocultured with nonconfluent retinal
      glial cells. CONCLUSIONS: Adverse effects of retinal glial cells on the survival
      of RGCs varied by size of the RGCs and retinal glial cell confluence. Glutamate
      and NO may be involved in retinal glial cell-related antisurvival effects.

PMID- 11581218
TI  - Hypoglycemia induces general neuronal death, whereas hypoxia and glutamate
      transport blockade lead to selective retinal ganglion cell death in vitro.
AB  - PURPOSE: To examine the impact of experimental ischemia and interruption of
      glutamate transport on retinal neuronal cell, especially retinal ganglion cell
      (RGC), survival in vitro. METHODS: Cell cultures were prepared from adult pig
      retinas and maintained under different experimental conditions of increasing
      hypoglycemia, environmental hypoxia (delayed postmortem period or atmospheric PO2
      <2%), or chemical hypoxia (potassium cyanide), or in the presence of glutamate
      transporter blockers L-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC) and L(-)
      threo-3-hydroxyaspartic acid (THA), or the glutamine synthetase inhibitor
      methionine sulfoximine (MS). After 48 hours, cells were returned to standard
      culture conditions and allowed to develop for 5 days, when they were fixed and
      immunostained with different retinal neuronal phenotypic markers. RESULTS:
      Control normoxic cultures contained large numbers of immunocytochemically
      identified photoreceptors (PRs), bipolar cells (BCs), amacrine cells (ACs), and
      RGCs after 7 days in vitro. A 24-hour postmortem delay before culture led to
      significant reductions in all types (40%-70%), proportionately greater in ACs and
      RGCs. Lowering of sugar levels also led to increased losses in all cell types,
      whereas potassium cyanide treatment deleteriously affected only ACs and RGCs.
      Ambient hypoxia led to consistent reductions only in the number of RGCs, which
      were exacerbated by addition of high concentrations of glutamate. Inclusion of
      glutamate receptor antagonists had a partial protective effect against RGC loss.
      Treatment with tPDC and THA also led to selective RGC death, but MS had no effect
      on any cells. CONCLUSIONS: Different components of the ischemic pathologic
      process (hypoxia, hypoglycemia, glutamate transport failure) lead to distinctly
      different patterns of neuronal loss in adult retina in vitro. RGCs are especially
      vulnerable, corresponding to their in vivo susceptibility. These data may suggest
      neuroprotective strategies for limiting retinal damage during ischemia.

PMID- 11581219
TI  - Downregulation of differentiation specific gene expression by oxidative stress in
      ARPE-19 cells.
AB  - PURPOSE: To investigate how the differentiation of ARPE-19 cells affects the
      relative expression of the FGFR genes in response to oxidative stress. METHODS:
      After differentiation in vitro, APRE-19 cells were treated with t-butyl
      hydroperoxide (tBH) or hydrogen peroxide (H2O2) to induce oxidative stress.
      Viability and reactive oxygen intermediate (ROI) production were measured using
      standard assays. The mRNA expression of FGFR1, FGFR2, cellular retinaldehyde
      binding protein (CRALBP), RPE65, and heme oxygenase-1 (HO-1) were measured by
      Northern blot analysis as a function of treatment with tBH and H2O2. RESULTS:
      ARPE-19 cells were viable at all tBH concentrations tested but showed progressive
      loss of viability at concentrations greater than 300 microM H2O2. Differentiated
      ARPE-19 cells treated with tBH or H2O2 resulted in upregulation of the HO-1 and
      FGFR1 transcripts. The expression of RPE-differentiated specific genes, including
      FGFR2, CRALBP, and RPE65 mRNAs, was downregulated with tBH or H2O2 treatment.
      CONCLUSIONS: Oxidative stress in differentiated ARPE-19 cells alters the
      expression of FGFR1, FGFR2, CRALBP, and RPE65 toward levels characteristic of the
      undifferentiated state. If similar changes take place in vivo, these events could
      alter the proliferative potential, viability, and even the function of the RPE.

PMID- 11581220
TI  - Oxidized low density lipoprotein-induced inhibition of processing of
      photoreceptor outer segments by RPE.
AB  - PURPOSE: To examine the effects of oxidized low-density lipoproteins (oxLDL) on
      phagocytosis and processing of photoreceptor outer segments (OS) by retinal
      pigment epithelial (RPE) cells. METHODS: Confluent cultures of RPE-J cells were
      pretreated with oxLDL or LDL, and the effects of such treatment on the processing
      of added OS was determined. Processing was determined either by the degradation
      of 125I-labeled OS to trichloroacetic acid-soluble label or by the cleavage of
      rhodopsin observed on Western blot analysis of cell lysates separated by sucrose
      density gradient fractionation. Binding to and uptake of OS by RPE-J cells was
      assessed by determining the fluorescence of FITC-labeled OS before and after
      quenching with trypan blue. RESULTS: OxLDL induced a significant decrease in the
      degradation of 125I-OS in RPE-J cells but no reductions in either binding or
      uptake, when a 24-hour recovery period was inserted between treatment with oxLDL
      and challenge with OS. Rhodopsin cleavage increased in a time-dependent manner
      after phagocytosis of OS by RPE-J cells. The small guanosine triphosphatase
      (GTPase), Rab5, was first found in phagosome fractions containing rhodopsin and
      its cleavage products, and at later times of challenge, in more dense fractions
      representing phagolysosomes. These were assessed by the colocalization of
      rhodopsin cleavage products in density fractions with cathepsin D, a marker of
      lysosomes. OxLDL induced a reduction in rhodopsin cleavage product formation and
      in phagosome-lysosome fusion (maturation). It also reduced the time-dependent
      shift of rhodopsin to higher density fractions containing more cathepsin D
      without any detectable reduction in the expression of cathepsin D or in acid
      protease activity. CONCLUSIONS: OxLDL induces a reduction in the processing of OS
      by RPE by perturbing the fusion of lysosomes with phagosomes.

PMID- 11581221
TI  - Contrast adaptation in human retina and cortex.
AB  - PURPOSE: Although cortical contrast adaptation has been extensively studied with
      both psychophysical and electrophysiological techniques, little is known about
      retinal contrast adaptation in humans. METHODS: Retinal and cortical long-term
      contrast adaptation was assessed with simultaneous measurement of pattern
      electroretinogram (PERG) and cortical visual evoked potentials (VEPs). This study
      involved three approaches: sampling of the contrast transfer function from 2.7%
      to 98% with adaptation to high (98%) and low (7.3%) contrasts, linearity of
      adaptation effects, and transfer of contrast adaptation between parallel and
      orthogonal grating orientations. RESULTS: Contrast adaptation affected retinal
      and cortical recordings quite differently. The VEP showed a sigmoid contrast
      transfer function, which was shifted toward higher contrasts (by a factor of
      1.9), whereas amplitudes at higher test contrasts were enhanced to 127%. The PERG
      decreased in amplitude to approximately 90%, and the latency was significantly
      reduced by 4 to 6 msec (P < 0.05). All measured effects were linear with
      adaptation contrast. Orientation played no role in the PERG results, whereas the
      VEP was enhanced to 125% when tested parallel and to 150% when tested orthogonal
      to adaptation. CONCLUSIONS: VEP results confirm and extend previous findings and
      fit well with single-cell recordings. The PERG findings suggest that retinal
      contrast adaptation occurs and mainly operates in the temporal domain, comparable
      to rapid gain-control findings in cats and primates.

PMID- 11581222
TI  - Slow and fast rod ERG pathways in patients with X-linked complete stationary
      night blindness carrying mutations in the NYX gene.
AB  - PURPOSE: To study the slow and fast rod signals of the scotopic 15-Hz flicker ERG
      in patients carrying mutations in the NYX gene, which has been recently
      identified as the cause of the complete form of congenital stationary night
      blindness, CSNB1. METHODS: Twenty eyes of 11 patients with CSNB1 who had
      nondetectable standard ERG rod b-waves were involved in the study. Scotopic ERG
      response amplitudes and phases to flicker intensities ranging from -3.37 to -0.57
      log scotopic trolands. sec (scot td. sec) were measured at a flicker frequency of
      15 Hz. ERG signals to flicker intensities between -3.37 and -1.97 and between 
      1.17 and -0.57 log scot td. sec were considered to represent primarily the slow
      and fast rod ERG pathway, respectively. Additionally, standard ERGs were
      performed. Twenty-two normal volunteers served as control subjects. RESULTS: For
      the slow rod ERG pathway, all patients exhibited ERG signals that were
      indistinguishable from noise. Accordingly, there was no systematic phase behavior
      for the slow rod signals. For the fast rod ERG pathway, the signals were
      significantly above noise, but they were significantly reduced in amplitude and
      advanced in phase. CONCLUSIONS: There is evidence that the slow and the fast rod
      ERG signals can be attributed to the rod bipolar-AII cell pathway and the rod
      cone-coupling pathway, respectively. The current study provides evidence to
      suggest that a defective NYX gene product (nyctalopin) prevents detectable signal
      transmission through ON rod bipolar cells, but there is a residual transmission
      through rod-cone gap junctions in CSNB1, possibly through the OFF cone pathway.

PMID- 11581223
TI  - Deficit of visual contour integration in dyslexia.
AB  - PURPOSE: The visual processing of text occurs spontaneously in most readers.
      Dyslexic persons, however, often report both somatic symptoms and perceptual
      distortions when trying to read. It is possible that the perceptual distortions
      experienced by those with dyslexia reflect a disturbance in the basic mechanisms
      supporting perceptual organization at the early stages of visual processing.
      Integration of information over extended areas of visual space can be measured
      psychophysically in a task that requires the detection of a path defined by
      aligned, spatially narrow-band elements on a dense field of otherwise similar
      elements that are randomly oriented and positioned. In the present study a
      contour integration task was used to investigate such perceptual organization in
      dyslexia. METHODS: The detection of contours or paths composed of Gabor
      micropatterns was performed within a field of randomly oriented distracter
      elements in a 2-alternate forced choice (AFC) task. The stimuli were manipulated
      by randomly varying both the density of the background noise elements and the
      number of elements that defined a path of constant length. RESULTS: In all
      observers, sensitivity to the paths increased with the number of target elements
      comprising the path, and subjects in both groups exhibited similar trends in
      relative density of the stimuli. However, in all conditions, dyslexic observers
      were two to three times less sensitive to path stimuli than the control group.
      CONCLUSIONS: In the present study the authors have described a visual deficit in
      a global integration task in dyslexia. The pattern of deficits reported suggest
      that abnormal cooperative associations may be present in dyslexia that are
      indicative of poor perceptual integration.

PMID- 11581224
TI  - The problem with cephalosporins.
AB  - The cephalosporin antibiotics have become a major part of the antibiotic
      formulary for hospitals in affluent countries. They are prescribed for a wide
      variety of infections every day. Their undoubted popularity relies upon lesser
      allergenic and toxicity risks as well as a broad spectrum of activity. It is the
      latter feature, however, that encourages the selection of microorganisms that are
      resistant to these agents. There are long-term implications for the treatment and
      control of this heterogeneous group of superinfections. When clinicians evaluate
      a septic patient, it is understandable that they choose empirical therapy with a
      cephalosporin whilst awaiting microbiology and other tests, since bacterial
      identification and antimicrobial testing still usually require 24-48 h. The broad
      spectrum capability of these drugs, however, encourages rapid overgrowth of some
      microorganisms that are neither eliminated nor inhibited by therapy. These
      organisms not only have pathogenic potential, they may also be multiply resistant
      to antibiotics. This review discusses the evidence that cephalosporin usage is
      the most important factor in the selection and propagation of microorganisms such
      as Clostridium difficile, methicillin-resistant Staphylococcus aureus, penicillin
      resistant pneumococci, multiply resistant coliforms and vancomycin-resistant
      enterococci, the continuing increase of which threatens the future of
      antimicrobial therapy.

PMID- 11581225
TI  - Effect of different classes of inhibitors on DNA gyrase from Mycobacterium
      smegmatis.
AB  - Quinolones, coumarins, cyclothialidines, CcdB and microcin B17 inhibit DNA
      gyrase. Information regarding these various inhibitors comes from studies
      performed with the enzyme from Escherichia coli, and subsequent analyses have
      also primarily been confined to this system. We have carried out a detailed
      analysis of the effect of various groups of inhibitors on Mycobacterium smegmatis
      gyrase and demonstrate differential susceptibility of the E. coli and M.
      smegmatis gyrases. Interestingly, M. smegmatis gyrase was refractory to the
      plasmid-borne proteinaceous inhibitors CcdB and microcin B17. Ciprofloxacin, a
      fluoroquinolone, showed a 10-fold reduction in efficacy against M. smegmatis
      compared with E. coli gyrase. We have also shown that etoposide, an
      antineoplastic drug, inhibits DNA gyrase activity by trapping the gyrase-DNA
      complex. DNA gyrases from both E. coli and M. smegmatis were susceptible to
      etoposide at comparable levels.

PMID- 11581226
TI  - Antibacterial action of several tannins against Staphylococcus aureus.
AB  - We examined the antibacterial action of several tannins on plasma coagulation by
      Staphylococcus aureus and the effect of conventional chemotherapy combined with
      tannic acid below the MIC. Coagulation was inhibited in plasma containing tannic
      acid (100 mg/L), gallic acid (5000 mg/L), ellagic acid (5000 mg/L), (-)
      epicatechin (1500 mg/L), (-)-epicatechin gallate (500 mg/L) or (-)
      epigallocatechin gallate (200 mg/L) after incubation for 24 h. All tannins
      inhibited coagulation at a concentration below the MIC. The MICs of oxacillin and
      cefdinir for S. aureus were reduced to < or = 0.06 mg/L in Mueller-Hinton agar
      plates with tannic acid (100 mg/L) at a concentration below the MIC. The
      antistaphylococcal activity of tannic acid was reduced in plates with 10% rabbit
      blood, but not in those with 10% rabbit plasma. Membranous structures formed in a
      culture medium containing equal proportions of plasma and tryptic soy broth after
      incubation for 24 h. The colony counts of S. aureus in membranous structures in
      the medium containing oxacillin (40 mg/L) and tannic acid (100 mg/L) were c. 10
      fold lower than those in medium containing oxacillin (40 mg/L) alone (P < 0.01).
      Tannic acid merits further investigation as a possible adjuvant agent against S.
      aureus skin infections treated with beta-lactam antibiotics.

PMID- 11581227
TI  - A procedure for evaluation and documentation of susceptibility test methods using
      the susceptibility of Klebsiella pneumoniae to ciprofloxacin as a model.
AB  - A new procedure for the evaluation and documentation of susceptibility test
      methods is described. To illustrate the procedure, four basically different
      susceptibility test methods were examined in a routine laboratory. The test
      parameter detection of decreased susceptibility to ciprofloxacin (breakpoint MIC
      0.25 mg/L) among 94 selected isolates of Klebsiella pneumoniae was used. In
      addition to comparison of frequency histograms and regression analysis, the
      accuracies of the susceptibility test methods were determined using the receiver
      operating characteristic procedure. For each of the methods, the sensitivity
      (SN), specificity (SP), positive predictive value (PV+) and negative predictive
      value (PV-) for detection of decreased susceptibility to ciprofloxacin were
      calculated and plotted against a range of ciprofloxacin inhibition zones
      determined by the various susceptibility test methods or MICs determined by the
      Etest (Etest MICs). The results illustrate the accuracy and the robustness of the
      methods, which can be used to expose the need for training and instruction of
      laboratory staff. It becomes possible to optimize and justify the choice of
      inhibition zone breakpoints or Etest MIC breakpoints according to the SN and SP
      of the method employed. Furthermore, the consequences of adjustments of these
      breakpoints on the PV+ and PV- can be analysed and related to different clinical
      and epidemiological situations. We believe that our approach can be used as a
      model for the evaluation and documentation of susceptibility test methods in
      general.

PMID- 11581228
TI  - Ex vivo 12 h bactericidal activity of oral co-amoxiclav (1.125 g) against beta
      lactamase-producing Haemophilus influenzae.
AB  - The aim of the study was to evaluate the in vitro/ex vivo bactericidal activity
      of a new coamoxiclav single-dose sachet formulation (1 g amoxicillin + 0.125 g
      clavulanic acid) against a beta-lactamase-producing strain of Haemophilus
      influenzae. The evaluation covered the 12 h period after antibiotic
      administration. Serum specimens from the 12 healthy volunteers included in the
      pharmacokinetic study were pooled by time point and in equal volumes. Eight of 12
      pharmacokinetic sampling time points were included in the study. At time points
      0.5, 0.75, 1, 1.5, 2.5, 5, 8 and 12 h post-dosing, the kinetics of bactericidal
      activity were determined for each of the serial dilutions. Each specimen was
      serially diluted from 1:2 to 1:256. The index of surviving bacteria (ISB) was
      subsequently determined for each pharmacokinetic time point. For all the serum
      samples, bactericidal activity was fast (3-6 h), marked (3-6 log(10) reduction in
      the initial inoculum) and sustained over the 12 h between-dosing interval. The
      results obtained also confirmed that the potency of the amoxicillin plus
      clavulanic acid combination was time dependent against the species under study
      and that the time interval over which the concentrations were greater than the
      MIC (t > MIC) was 100% for the strain under study. The data thus generated
      constitute an interesting prerequisite with a view to using co-amoxiclav 1.125 g
      in a bd oral regimen.

PMID- 11581229
TI  - Prototype trial design for rapid dose selection of antiretroviral drugs: an
      example using emtricitabine (Coviracil).
AB  - Antiretroviral monotherapy for initial drug characterization risks the selection
      of resistant virus, yet monotherapy is the only setting where many fundamental
      properties of a new drug can be reliably determined. Using data on viral
      replication kinetics and dynamics, we designed an accelerated (14 day) open-label
      study of single agent emtricitabine (formerly known as FTC)--a nucleoside reverse
      transcriptase inhibitor--to select a dosing regimen for further therapeutic
      study. Five regimens (25 mg bd, 100 mg od, 200 mg od, 100 mg bd and 200 mg bd)
      were evaluated in HIV-1-infected subjects over a 14 day dosing period to
      determine the optimal dose and pharmacokinetics. Serial blood samples for
      virological, pharmacokinetic and intracellular FTC-triphosphate measurements were
      drawn frequently. A dose-response relationship for the antiviral activity of
      emtricitabine was established, with total daily doses of 200 mg or more producing
      the greatest median HIV-1 viral load suppression: 1.72-1.92 log10. Based on
      virological outcomes, dose-response analysis and intracellular triphosphate
      levels, a once-daily dose of 200 mg was selected for further long-term clinical
      study. Adverse events possibly related to emtricitabine were unremarkable. The
      antiviral activity of emtricitabine correlated well with intracellular FTC
      triphosphate concentrations. This study design is a safe, useful tool for early
      dose selection for drugs with potent antiretroviral activity and linear
      pharmacokinetics.

PMID- 11581230
TI  - Treatment of Trypanosoma cruzi-infected children with nifurtimox: a 3 year follow
      up by PCR.
AB  - Patients suffering from Chagas' disease, as determined by positive serological
      results, were tested for further evidence of Trypanosoma cruzi infection by
      xenodiagnosis and PCR. The patients included 67 children aged from 0 to 10 years
      and 75 adults. All children were positive by PCR on their pre-therapy sample,
      while only 69% of the seropositive adults and none of the 78 seronegative control
      adults were PCR positive. Xenodiagnosis was positive in 79% of the children, but
      only in 21% of the adults. A group of 66 children was treated with nifurtimox,
      and followed up every 3 months during the first year and every 6 months during
      the second and third year post-therapy, by PCR, xenodiagnosis and serology. We
      concluded that PCR was the most effective test to monitor children for 3 years
      post-chemotherapy, when all the cases converted from positive to negative.
      Conventional serology, however, remained positive after that period in most
      cases. In contrast, conversion to negative xenodiagnosis occurred very early
      after treatment.

PMID- 11581232
TI  - Cefepime versus cefotaxime for empirical treatment of bacterial pneumonia in HIV
      infected patients: an open, randomized trial.
AB  - An open, randomized, multicentre clinical trial was conducted to compare the
      efficacy and safety of cefepime 2 g iv bd (2 g tds daily in cases of Pseudomonas
      aeruginosa pneumonia) with cefotaxime 2 g iv tds, in the empirical treatment of
      bacterial pneumonia in HIV-infected patients. The primary end-point was
      effectiveness after 3-5 days of treatment, taking success to be when the study
      drug was continued during this period of time. Clinical and bacteriological
      responses at end of treatment (EOT) were also evaluated. Analyses of the
      intention-to-treat population (n = 160) and the as-per-protocol groups (n = 150)
      were carried out. Treatment groups were comparable with regard to sex, age, HIV
      status and degree of severity of pneumonia. The primary end-point for cefepime
      was considered successful for the intention-to-treat and as-per-protocol groups
      in 85.7% and 93.5% of cases, respectively, and for cefotaxime, in 77.6% and 80.8%
      of cases, respectively (P = 0.22 and P = 0.02). In the as-per-protocol group,
      cefotaxime treatment was independently related to failure at the primary end
      point. A satisfactory clinical response in the intention-to-treat population was
      observed in 83.3% of cefepime and 82.9% of cefotaxime patients. Bacteriological
      cure was obtained in 100% of evaluable cefepime and 93.4% of evaluable cefotaxime
      patients at EOT. Safety of the study drugs was comparable in both treatment
      groups. Cefepime 2 g iv bd was at least as effective and as well tolerated as
      cefotaxime 2 g iv tds in the treatment of bacterial pneumonia in HIV-infected
      patients.

PMID- 11581231
TI  - Breakthrough fungaemia in neonates and infants caused by Candida albicans and
      Candida parapsilosis susceptible to fluconazole in vitro.
AB  - Breakthrough fungaemias due to Candida albicans and Candida parapsilosis
      appearing during fluconazole therapy in neonates and infants were assessed for
      risk factors and outcome. Forty fungaemias occurred during therapy with
      fluconazole within a 12 year national survey and were compared with 161 cases of
      non-breakthrough paediatric fungaemias. The agar disc diffusion test method was
      used for antifungal susceptibility testing and the Vitek system for species
      identification. Univariate and multivariate analysis for risk factors for
      breakthrough fungaemia were carried out. All the fungaemias were a result of
      strains susceptible to fluconazole at 0.25-4 mg/L in vitro [C. albicans (85%) and
      C. parapsilosis (15%)]. The mean number of positive blood cultures per episode
      was 2.2. Sixteen children had 'early' breakthrough fungaemias (within 4-5 days)
      and 24 fungaemias appeared on day 6 and later. Mean fluconazole MICs in the
      'early' group were 1.2, and 2.8 mg/L in the 'late' group (P < 0.03, t-test).
      However, no difference was observed in the average dose of fluconazole used in
      the two groups. Neonatal age, total parenteral nutrition, very low birth weight,
      before surgery, central or umbilical venous catheterization and artificial
      ventilation were all significantly related to breakthrough fungaemia in
      univariate analysis but only central or umbilical venous catheterization were
      significant in multivariate analysis. The outcome of breakthrough fungaemia was
      better overall and attributable mortalities in non-breakthrough fungaemia was
      significantly higher in comparison with breakthrough fungaemia.

PMID- 11581233
TI  - Departmental consumption of antibiotic drugs and subsequent resistance: a
      quantitative link.
AB  - OBJECTIVE: To look for a quantitative model linking departmental consumption of
      antibiotic drugs to the subsequent isolation of resistant hospital-acquired
      coliform pathogens. MATERIALS AND METHODS: Included in the study were all
      patients with hospital-acquired bloodstream infections caused by a coliform
      pathogen, detected in six departments of internal medicine of one university
      hospital during the period 1991-1996, who had not been hospitalized in the month
      before the infection (n = 394). Departmental consumption of antibiotics in the
      year before the infection [expressed as defined daily dosages (DDD)/100 patient
      days], antibiotic treatment given to the individual patient before the infection,
      the day of hospital stay on which the infection occurred, and the department and
      the calendar year were all included in a logistic model to predict the isolation
      of a resistant pathogen. We looked at five drugs: gentamicin, amikacin,
      cefuroxime, ceftazidime and ciprofloxacin. RESULTS: Five logistic models were
      fitted for the resistance to each of the antibiotic drugs. The multivariable
      adjusted odds ratios for a pathogen resistant to the specific antibiotic were
      1.03 [95% confidence interval (CI) 0.70-1.50] for gentamicin, 1.80 (95% CI 1.00
      3.24) for amikacin, 1.12 (95% CI 1.02-1.23) for cefuroxime, 1.45 (95% CI 1.19
      1.76) for ceftazidime and 1.06 (95% CI 0.57-1.97) for ciprofloxacin, per 1
      DDD/100 patient days. CONCLUSIONS: The departmental consumption of cephalosporin
      drugs and amikacin in six autonomous departments of medicine in the same hospital
      was associated with a measurable and statistically significant increase in the
      probability of infection caused by a resistant pathogen.

PMID- 11581234
TI  - Detection of macrolide resistance mechanisms in Streptococcus pneumoniae and
      Streptococcus pyogenes using a multiplex rapid cycle PCR with microwell-format
      probe hybridization.
AB  - In this study, a multiplex rapid cycle PCR with microwell-format probe
      hybridization method was developed to perform high-volume screening for macrolide
      resistance determinants in isolates of Streptococcus pneumoniae and Streptococcus
      pyogenes. The method was then utilized to determine the distribution of macrolide
      resistance mechanisms in recent isolates of S. pneumoniae and S. pyogenes from
      Great Britain and Ireland. For 83 strains of macrolide resistant S. pneumoniae
      tested, 51 (61.4%) were positive for mef(A), 29 (34.9%) erm(B), two (2.4%) double
      mechanisms mef(A) + erm(B), and one (1.2%) negative for all mechanisms tested.
      For 56 strains of macrolide-resistant S. pyogenes tested, 33 (58.9%) were
      positive for erm(A) subclass erm(TR), 18 (32.1%) mef(A) and five (8.9%) erm(B).

PMID- 11581235
TI  - Frequency of selection of fluoroquinolone-resistant mutants of Neisseria
      gonorrhoeae exposed to gemifloxacin and four other quinolones.
AB  - We studied the frequency of mutation of clinical isolates of Neisseria
      gonorrhoeae (two nalidixic acid susceptible and two nalidixic acid resistant),
      and the stability of the mutants obtained, in the presence of three different
      concentrations of five fluoroquinolones. The frequency of mutation was low for
      all the quinolones. Only one N. gonorrhoeae mutant, obtained with trovafloxacin
      at 4 x MIC presented a stable increase in the MIC of this quinolone, not
      attributable to novel mutation(s), both in the gyrA and parC genes, although not
      showing any increase in the MIC of the other quinolones tested. In summary,
      gemifloxacin was the only quinolone tested for which resistant mutants were not
      obtained.

PMID- 11581236
TI  - Fluoroquinolone susceptibilities of efflux-mediated multidrug-resistant
      Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia.
AB  - The antibacterial activities of seven fluoroquinolones (ciprofloxacin, BAYy3118,
      clinafloxacin, gemifloxacin, moxifloxacin, sparfloxacin and trovafloxacin)
      against isogenic efflux-mediated multidrug-resistant strains of Pseudomonas
      aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia, were compared.
      The results indicate that these fluoroquinolones are all substrates for the
      multidrug efflux systems of these organisms. Clinafloxacin was found generally to
      be the most active agent against multidrug-resistant strains.

PMID- 11581237
TI  - In vivo selection of a target/efflux double mutant of Pseudomonas aeruginosa by
      ciprofloxacin therapy.
AB  - We report the emergence after 4 days of ciprofloxacin monotherapy of a double
      mutant of Pseudomonas aeruginosa overexpressing the multidrug efflux system MexAB
      OprM and harbouring a mutation in the gyrB gene. Compared with its initial
      susceptible counterpart, this mutant exhibited a significant increase in
      resistance to most of the beta-lactam antibiotics tested (16 x MIC of
      ticarcillin) and to ciprofloxacin (128 x MIC). Combined ceftazidime and amikacin
      therapy finally eradicated the resistant isolate and cured the patient of his
      infection. This case illustrates how strains of P. aeruginosa may develop high
      levels of fluoroquinolone resistance by combining efflux mechanisms and target
      alterations.

PMID- 11581238
TI  - Evaluation of daptomycin susceptibility testing by Etest and the effect of
      different batches of media.
AB  - One hundred and ninety-five Gram-positive bacteria representing 17 species were
      tested for susceptibility to daptomycin by broth microdilution and Etest methods.
      The geometric mean daptomycin MIC was 0.46 mg/L by broth microdilution tests and
      0.73 mg/L by Etest. The concentration of calcium in 12 different batches of agar
      varied from 4 to 36 mg/L. Daptomycin Etest MICs varied inversely with the calcium
      concentration. Etest daptomycin MICs for quality control strains were within
      proposed quality control range on media with >20 mg/L of calcium. Monitoring the
      calcium levels of agar media by testing appropriate quality control strains is
      important for daptomycin Etests.

PMID- 11581239
TI  - Activity of daptomycin against Gram-positive pathogens: a comparison with other
      agents and the determination of a tentative breakpoint.
AB  - The in vitro activity of daptomycin was studied in comparison with other agents
      active against 328 recent clinical isolates of Gram-positive pathogens. MIC data
      showed that the addition of calcium ions to a final concentration of 50 mg/L
      enhanced the activity of daptomycin generally by eight- to 16-fold. In the
      presence of calcium ions daptomycin was uniformly active against the strains of
      Staphylococcus spp. and Streptococcus spp. studied with a MIC90 of < or = 1 mg/L.
      Enterococcus faecalis and Enterococcus faecium were slightly less susceptible
      (MIC90 2 mg/L). Vancomycin-, fluoroquinolone- and quinupristin/dalfopristin
      resistant strains were all susceptible to daptomycin. The presence of serum
      reduced the apparent activity of daptomycin to only a moderate extent. Employing
      the BSAC methodologies, a tentative breakpoint of 2 mg/L for daptomycin is
      proposed.

PMID- 11581240
TI  - Post-antibiotic effect of the antimicrobial peptide lactoferricin on Escherichia
      coli and Staphylococcus aureus.
AB  - Lactoferricin is an antimicrobial peptide generated by gastric pepsin cleavage of
      lactoferrin. A possible post-antibiotic effect (PAE) of bovine lactoferricin
      (Lfcin B) and two shorter peptide derivatives against Staphylococcus aureus and
      Escherichia coli was studied. A drug removal technique involving centrifugation
      and washing was used. No PAE was found for Lfcin B against these two bacteria.
      The shorter derivatives had a short PAE against E. coli. They had a short
      negative PAE against S. aureus. In conclusion, the overall PAE is not
      overwhelming, but the small differences found between the different peptide
      bacteria combinations could indicate that different peptide mechanisms of action
      might be present.

PMID- 11581241
TI  - A combination of roxithromycin and imipenem as an antimicrobial strategy against
      biofilms formed by Staphylococcus aureus.
AB  - We examined the effects of a combination of roxithromycin and imipenem on a
      biofilm model of Staphylococcus aureus. Treatment with roxithromycin alone and
      imipenem alone did not decrease the number of viable bacterial cells compared
      with the control. However, a combination treatment of roxithromycin and imipenem
      significantly decreased the number of viable bacterial cells on day 8 after
      inoculation in the in vivo model (P < 0.01). On days 5 and 8 after inoculation,
      numerous polymorphonuclear leucocytes and macrophages invaded the bacterial
      clusters in the roxithromycin- and roxithromycin/imipenem-treated groups, but did
      not invade the control or imipenem-treated groups. The present study indicated
      that a combination of roxithromycin and imipenem is a potentially effective
      treatment for S. aureus biofilm-associated skin infections as it can induce the
      invasion of polymorphonuclear leucocytes into the biofilm.

PMID- 11581242
TI  - Change of antimicrobial susceptibility of group B streptococci over 15 years in
      Japan.
AB  - We compared antimicrobial susceptibility patterns of 206 group B streptococcal
      (GBS) strains isolated from pregnant women and six from neonates/infants with
      invasive infection during the two periods 1985-1986 and 1999-2000. All strains in
      both periods were susceptible to the penicillins, cephalosporins and carbapenem
      tested. Seven (3%) isolates were resistant to erythromycin and three (1%) were
      resistant to clindamycin. There were no significant differences between the two
      study periods in the incidence of GBS resistant to the 14 antibiotics tested.
      These results showed that penicillins are still the first choice to prevent
      vertical transmission of GBS in Japan.

PMID- 11581243
TI  - Treatment of Absidia corymbifera infection in mice with amphotericin B and
      itraconazole.
AB  - The activities of amphotericin B and itraconazole were studied in a temporarily
      neutropenic murine model of disseminated Absidia corymbifera infection, caused by
      two different strains. Amphotericin B MICs were 0.25 mg/L for both strains and
      itraconazole MICs were 1 and 2 mg/L. Amphotericin B was effective in vivo with
      both isolates. Itraconazole was less effective.

PMID- 11581244
TI  - Antimicrobial resistance in Escherichia coli isolates from turkeys and hens in
      Ireland.

PMID- 11581245
TI  - Induction of in vitro resistance to BMS-284756 by Streptococcus pneumoniae.

PMID- 11581246
TI  - Activity of linezolid against levofloxacin-resistant Streptococcus pneumoniae,
      methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci
      in Hong Kong.

PMID- 11581247
TI  - High prevalence of erythromycin-resistant and clindamycin-susceptible (M
      phenotype) viridans group streptococci from pharyngeal samples: a reservoir of
      mef genes in commensal bacteria.

PMID- 11581248
TI  - Enhanced decrease of blood colony counts by specific anti-pneumococcal antibodies
      in the presence of sub-inhibitory concentrations of amoxicillin.

PMID- 11581249
TI  - Phosphatidylinositol-4-phosphate 5-kinase-1beta is essential for epidermal growth
      factor receptor-mediated endocytosis.
AB  - Phosphatidylinositol-4,5-bisphosphate (PIP(2)) is known to play an important role
      in signal transduction and membrane trafficking. We show that one enzyme
      responsible for PIP(2) production, phosphatidylinositol-4-phosphate 5-kinase type
      1beta (PIPKbeta), is essential for epidermal growth factor receptor (EGFR)
      mediated endocytosis. Expression of murine PIPKbeta in NR6 cells expressing EGFR
      strikingly increased receptor internalization. Moreover, the kinase was shown to
      form an immunoprecipitable complex with EGFR. Expression of either a truncated
      kinase or a kinase dead mutant inhibited EGFR endocytosis and also blocked the
      membrane recruitment of PIPKbeta and both clathrin light chain and dynamin. Our
      results delineate a novel mechanism by which PIPKbeta regulates receptor-mediated
      endocytosis and receptor tyrosine kinase membrane traffic.

PMID- 11581250
TI  - Characteristics and sequence of phosphoglycolate phosphatase from a eukaryotic
      green alga Chlamydomonas reinhardtii.
AB  - Phosphoglycolate phosphatase (PGPase), a key enzyme of photorespiration in
      photosynthetic organisms, was purified from Chlamydomonas reinhardtii. The enzyme
      was an approximately 65-kDa homodimer with a pI value of 5.1 composed of
      approximately 32-kDa subunits not connected by any S-S bridges. It was also
      highly specific for phosphoglycolate with a K(m) value of 140 microm and an
      optimal pH between 8 and 9. The activity was strongly inhibited by CaCl(2), and
      it recovered competitively following the addition of MgCl(2) or EGTA. A mobility
      shift was observed in SDS-polyacrylamide gel electrophoresis by the addition of
      CaCl(2), indicating that the enzyme binds to Ca(2+). The N-terminal region of
      amino acid sequence deduced from cDNA sequence that was not contained in the
      purified PGPase had similar characteristics to those of typical stroma-targeting
      transit peptides in C. reinhardtii. The following region of the deduced sequence
      containing 302 amino acid residues was similar to p-nitrophenylphosphatase-like
      proteins, although the purified PGPase did not hydrolyze p-nitrophenylphosphate.
      Genomic DNA fragments from wild type containing the sequence homologous to the
      cDNA for PGPase complemented the PGPase-deficient mutant pgp1. Possible
      regulatory mechanisms during adaptation to limiting CO(2) were discussed based on
      the characteristics of the purified PGPase and the deduced amino acid sequence.

PMID- 11581251
TI  - Stimulation of lipolysis and hormone-sensitive lipase via the extracellular
      signal-regulated kinase pathway.
AB  - Hormonally stimulated lipolysis occurs by activation of cyclic AMP-dependent
      protein kinase (PKA) which phosphorylates hormone-sensitive lipase (HSL) and
      increases adipocyte lipolysis. Evidence suggests that catecholamines not only can
      activate PKA, but also the mitogen-activated protein kinase pathway and
      extracellular signal-regulated kinase (ERK). We now demonstrate that two
      different inhibitors of MEK, the upstream activator of ERK, block catecholamine-
      and beta(3)-stimulated lipolysis by approximately 30%. Furthermore, treatment of
      adipocytes with dioctanoylglycerol, which activates ERK, increases lipolysis,
      although MEK inhibitors decrease dioctanoylglycerol-stimulated activation of
      lipolysis. Using a tamoxifen regulatable Raf system expressed in 3T3-L1
      preadipocytes, exposure to tamoxifen causes a 14-fold activation of ERK within 15
      30 min and results in approximately 2-fold increase in HSL activity. In addition,
      when differentiated 3T3-L1 cells expressing the regulatable Raf were exposed to
      tamoxifen, a 2-fold increase in lipolysis is observed. HSL is a substrate of
      activated ERK and site-directed mutagenesis of putative ERK consensus
      phosphorylation sites in HSL identified Ser(600) as the site phosphorylated by
      active ERK. When S600A HSL was expressed in 3T3-L1 cells expressing the
      regulatable Raf, tamoxifen treatment fails to increase its activity. Thus,
      activation of the ERK pathway appears to be able to regulate adipocyte lipolysis
      by phosphorylating HSL on Ser(600) and increasing the activity of HSL.

PMID- 11581252
TI  - Olfaction in the gypsy moth, Lymantria dispar: effect of pH, ionic strength, and
      reductants on pheromone transport by pheromone-binding proteins.
AB  - The pheromone-binding proteins (PBPs) are 16-kDa abundant proteins in specialized
      olfactory hairs in insects. The mechanism by which the PBPs remove the pheromone
      from the inner surface of sensory hairs and deliver it to the sensory cell
      remains unclear. Existing qualitative models postulate that pheromone is released
      near the dendrite by a decrease in pH or by a reduced form of the PBP. This study
      focuses on the two PBPs from the gypsy moth and the enantiomers of the pheromone
      cis-2-methyl-7,8-epoxyoctadecane. The pH dependence of pheromone binding has
      revealed three ionizations that are important. The type of ligand influences two
      of these ionizations. We propose that the (-)-enantiomer of the pheromone
      interacts with one of the ionizable residues on the protein while the (+)
      enantiomer does not. Simultaneous variation of pH and KCl concentration in the
      physiological range or reduction of disulfide bridges does not change the
      affinity of PBP for pheromone. We propose a revised model of pheromone transport
      from the inner surface of the sensory hair to the sensory neuron.

PMID- 11581253
TI  - Evidence for a novel role of copper-zinc superoxide dismutase in zinc metabolism.
AB  - The LYS7 gene in Saccharomyces cerevisiae encodes a protein (yCCS) that delivers
      copper to the active site of copper-zinc superoxide dismutase (CuZn-SOD, a
      product of the SOD1 gene). In yeast lacking Lys7 (lys7Delta), the SOD1
      polypeptide is present but inactive. Mutants lacking the SOD1 polypeptide
      (sod1Delta) and lys7Delta yeast show very similar phenotypes, namely poor growth
      in air and aerobic auxotrophies for lysine and methionine. Here, we demonstrate
      certain phenotypic differences between these strains: 1) lys7Delta cells are
      slightly less sensitive to paraquat than sod1Delta cells, 2) EPR-detectable or
      "free" iron is dramatically elevated in sod1Delta mutants but not in lys7Delta
      yeast, and 3) although sod1Delta mutants show increased sensitivity to
      extracellular zinc, the lys7Delta strain is as resistant as wild type. To restore
      the SOD catalytic activity but not the zinc-binding capability of the SOD1
      polypeptide, we overexpressed Mn-SOD from Bacillus stearothermophilus in the
      cytoplasm of sod1Delta yeast. Paraquat resistance was restored to wild-type
      levels, but zinc was not. Conversely, expression of a mutant CuZn-SOD that binds
      zinc but has no SOD activity (H46C) restored zinc resistance but not paraquat
      resistance. Taken together, these results strongly suggest that CuZn-SOD, in
      addition to its antioxidant properties, plays a role in zinc homeostasis.

PMID- 11581254
TI  - A low abundance pool of nascent p21WAF1/Cip1 is targeted by estrogen to activate
      cyclin E*Cdk2.
AB  - Estrogens regulate cell proliferation in target tissues, including breast cancer
      by stimulating G(1)-S phase transition. Activation of cyclin E.Cdk2 through
      abrogation of the ability of p21(WAF1/Cip1) to bind to and inhibit cyclin-CDKs is
      a pivotal event in this process in MCF-7 breast cancer cells. A proposed
      mechanism is p21 sequestration into cyclin D1.Cdk4/6 complexes driven by estrogen
      induced transcriptional activation of cyclin D1 gene expression. However, we now
      show that some E(2)-induced cyclin E.Cdk2 activation occurs in the absence of
      increased cyclin D1 levels and requires decreased p21 protein synthesis. Both
      mechanisms operate in the absence of major changes in total p21 protein levels
      and instead target a low abundance subset of newly synthesized p21. E(2)-induced
      activation of cyclin E.Cdk2 is mimicked by targeted inhibition of nascent p21
      expression by antisense p21 oligonucleotides. Cyclin E.Cdk2 activation is
      completely inhibited by a combination of antisense cyclin D1 oligonucleotide
      transfection and elimination of the decrease in nascent p21 by infection with
      adenoviral-p21. These findings strongly support a central role for p21 in the
      early phase of E(2)-induced mitogenesis and highlight a major functional role for
      newly synthesized CDK inhibitory proteins.

PMID- 11581255
TI  - Protein kinase C regulates FADD recruitment and death-inducing signaling complex
      formation in Fas/CD95-induced apoptosis.
AB  - Activation of protein kinase C (PKC) triggers cellular signals that inhibit
      Fas/CD95-induced cell death in Jurkat T-cells by poorly defined mechanisms.
      Previously, we have shown that one effect of PKC on Fas/CD95-dependent cell death
      occurs through inhibition of cell shrinkage and K(+) efflux (Gomez-Angelats, M.,
      Bortner, C. D., and Cidlowski, J. A. (2000) J. Biol. Chem. 275, 19609-19619).
      Here we report that PKC alters Fas/CD95 signaling from the plasma membrane to the
      activation of caspases by exerting a profound action on survival/cell death
      decisions. Specific activation of PKC with 12-O-tetradecanoylphorbol-13-acetate
      or bryostatin-1 induced translocation of PKC from the cytosol to the membrane and
      effectively inhibited cell shrinkage and cell death triggered by anti-Fas
      antibody in Jurkat cells. In contrast, inhibition of classical PKC isotypes with
      Go6976 exacerbated the effect of Fas activation on both apoptotic volume decrease
      and cell death. PKC activation/inhibition did not affect anti-Fas antibody
      binding to the cell surface, intracellular levels of FADD (Fas-associated protein
      with death domain), or c-FLIP (cellular FLICE-like inhibitory protein)
      expression. However, processing/activation of both caspase-8 and caspase-3 and
      BID cleavage were markedly blocked upon PKC activation and, conversely, were
      augmented during PKC inhibition, suggesting a role for PKC upstream of caspase-8
      processing and activation. Analysis of death-inducing signaling complex (DISC)
      formation was carried out to examine the influence of PKC on recruitment of both
      FADD and procaspase-8 to the Fas receptor. PKC activation blocked FADD
      recruitment and caspase-8 activation and thus DISC formation in both type I and
      II cells. In contrast, inhibition of classical PKCs promoted the opposite effect
      on the Fas pathway by rapidly increasing FADD recruitment, caspase-8 activation,
      and DISC formation. Together, these data show that PKC finely modulates Fas/CD95
      signaling by altering the efficiency of DISC formation.

PMID- 11581256
TI  - Crystal structure of MtaN, a global multidrug transporter gene activator.
AB  - MtaN (Multidrug Transporter Activation, N terminus) is a constitutive,
      transcriptionally active 109-residue truncation mutant, which contains only the N
      terminal DNA-binding and dimerization domains of MerR family member Mta. The 2.75
      A resolution crystal structure of apo-MtaN reveals a winged helix-turn-helix
      protein with a protruding 8-turn helix (alpha5) that is involved in dimerization
      by the formation of an antiparallel coiled-coil. The hydrophobic core and helices
      alpha1 through alpha4 are structurally homologous to MerR family member BmrR
      bound to DNA, whereas one wing (Wing 1) is shifted. Differences between the
      orientation of alpha5 with respect to the core and the revolution of the
      antiparallel coiled-coil lead to significantly altered conformations of MtaN and
      BmrR dimers. These shifts result in a conformation of MtaN that appears to be
      incompatible with the transcription activation mechanism of BmrR and suggest that
      additional DNA-induced structural changes are necessary.

PMID- 11581257
TI  - A novel C-terminal kinesin is essential for maintaining functional
      acidocalcisomes in Trypanosoma brucei.
AB  - Kinesins are cytoskeletal motor proteins that play roles in a variety of
      fundamental cellular processes including cell division and the anterograde
      transport of vesicles and organelles. We purified, cloned, and functionally
      characterized in Trypanosoma brucei a new member of the C-terminal kinesin
      family, TbKIFC1. Kinetic constants of the recombinant motor domain of TbKIFC1
      were estimated at 0.56 microm for the microtubule dissociation constant (K(d))
      with a k(cat) of 0.2 s(-1). Immunolocalization analysis showed an association of
      TbKIFC1 with punctate structures. Because they were rapidly transported to the
      negative pole of the microtubule after NH(4)Cl treatment, these structures were
      considered to be associated with acidic vesicles. To determine the role of the
      kinesin in vivo, we produced an inducible kinesin-deficient strain by double
      stranded RNA interference methodology. Mutant cells were loaded with the
      fluorescent reagent fura2/acetoxymethylester to measure intracellular free
      calcium ([Ca(2+)](i)). The resting [Ca(2+)](i) was unchanged in mutant cells;
      however, alkalinization of acidic vesicles induced by NH(4)Cl or nigericin was
      not followed by release of Ca(2+). These data and the relative importance of the
      ionomycin-releasable and the ionomycin-plus-NH(4)Cl-releasable Ca(2+) pools
      suggest a lower Ca(2+) content in acidocalcisomes and dysfunctional Ca(2+)
      release.

PMID- 11581258
TI  - The multispanning membrane protein Ste24p catalyzes CAAX proteolysis and NH2
      terminal processing of the yeast a-factor precursor.
AB  - Saccharomyces cerevisiae Ste24p is a multispanning membrane protein implicated in
      the CAAX proteolysis step that occurs during biogenesis of the prenylated a
      factor mating pheromone. Whether Ste24p acts directly as a CAAX protease or
      indirectly to activate a downstream protease has not yet been established. In
      this study, we demonstrate that purified, detergent-solubilized Ste24p directly
      mediates CAAX proteolysis in a zinc-dependent manner. We also show that Ste24p
      mediates a separate proteolytic step, the first NH(2)-terminal cleavage in a
      factor maturation. These results establish that Ste24p functions both as a bona
      fide COOH-terminal CAAX protease and as an a-factor NH(2)-terminal protease.
      Importantly, this study is the first to directly demonstrate that a eukaryotic
      multispanning membrane protein can possess intrinsic proteolytic activity.

PMID- 11581259
TI  - Identification and characterization of two distinct ligand binding regions of
      cubilin.
AB  - Using polymerase chain reaction-amplified fragments of cubilin, an endocytic
      receptor of molecular mass 460 kDa, we have identified two distinct ligand
      binding regions. Region 1 of molecular mass 71 kDa, which included the 113
      residue N terminus along with the eight epidermal growth factor (EGF)-like
      repeats and CUB domains 1 and 2, and region 2 of molecular mass 37 kDa consisting
      of CUB domains 6-8 bound both intrinsic factor-cobalamin (vitamin B(12); Cbl) (IF
      Cbl) and albumin. Within these two regions, the binding of both ligands was
      confined to a 110-115-residue stretch that encompassed either the 113-residue N
      terminus or CUB domain 7 and 8. Ca(2+) dependence of ligand binding or the
      ability of cubilin antiserum to inhibit ligand binding to the 113-residue N
      terminus was 60-65%. However, a combination of CUB domains 7 and 8 or 6-8 was
      needed to demonstrate significant Ca(2+) dependence or inhibition of ligand
      binding by cubilin antiserum. Antiserum to EGF inhibited albumin but not IF-Cbl
      binding to the N-terminal cubilin fragment that included the eight EGF-like
      repeats. While the presence of excess albumin had no effect on binding to IF-Cbl,
      IF-Cbl in excess was able to inhibit albumin binding to both regions of cubilin.
      Reductive alkylation of the 113-residue N terminus or CUB 6-8, CUB 7, or CUB 8
      domain resulted in the abolishment of ligand binding. These results indicate that
      (a) cubilin contains two distinct regions that bind both IF-Cbl and albumin and
      that (b) binding of both IF-Cbl and albumin to each of these regions can be
      distinguished and is regulated by the nonassisted formation of local disulfide
      bonds.

PMID- 11581260
TI  - Identification of a novel phosphonocarboxylate inhibitor of Rab geranylgeranyl
      transferase that specifically prevents Rab prenylation in osteoclasts and
      macrophages.
AB  - Nitrogen-containing bisphosphonate drugs inhibit bone resorption by inhibiting
      FPP synthase and thereby preventing the synthesis of isoprenoid lipids required
      for protein prenylation in bone-resorbing osteoclasts. NE10790 is a
      phosphonocarboxylate analogue of the potent bisphosphonate risedronate and is a
      weak anti-resorptive agent. Although NE10790 was a poor inhibitor of FPP
      synthase, it did inhibit prenylation in J774 macrophages and osteoclasts, but
      only of proteins of molecular mass approximately 22-26 kDa, the prenylation of
      which was not affected by peptidomimetic inhibitors of either farnesyl
      transferase (FTI-277) or geranylgeranyl transferase I (GGTI-298). These 22-26-kDa
      proteins were shown to be geranylgeranylated by labelling J774 cells with
      [(3)H]geranylgeraniol. Furthermore, NE10790 inhibited incorporation of
      [(14)C]mevalonic acid into Rab6, but not into H-Ras or Rap1, proteins that are
      modified by FTase and GGTase I, respectively. These data demonstrate that NE10790
      selectively prevents Rab prenylation in intact cells. In accord, NE10790
      inhibited the activity of recombinant Rab GGTase in vitro, but did not affect the
      activity of recombinant FTase or GGTase I. NE10790 therefore appears to be the
      first specific inhibitor of Rab GGTase to be identified. In contrast to
      risedronate, NE10790 inhibited bone resorption in vitro without markedly
      affecting osteoclast number or the F-actin "ring" structure in polarized
      osteoclasts. However, NE10790 did alter osteoclast morphology, causing the
      formation of large intracellular vacuoles and protrusion of the basolateral
      membrane into large, "domed" structures that lacked microvilli. The anti
      resorptive activity of NE10790 is thus likely due to disruption of Rab-dependent
      intracellular membrane trafficking in osteoclasts.

PMID- 11581261
TI  - Characterization of the dimerization domain in the FNR transcription factor.
AB  - The global anaerobic regulator FNR from Escherichia coli is a dimeric Fe-S
      protein that is inactivated by O(2) through disruption of its [4Fe-4S] cluster
      and conversion to a monomeric form. As a first step in elucidating the molecular
      interactions that control FNR dimerization, we have performed alanine-scanning
      mutagenesis of a potential dimerization domain. Replacement of many hydrophobic
      residues (Met-143, Met-144, Leu-146, Met-147, Ile-151, Met-157, and Ile-158) and
      two charged residues (Arg-140 and Arg-145) with Ala decreased FNR activity in
      vivo. Size exclusion chromatography and Fe-S cluster analysis of three
      representative mutant proteins, FNR-M147A, FNR-I151A, and FNR-I158A, showed that
      the Ala substitutions produced specific defects in dimerization. Because
      hydrophobic side chains are known to stabilize subunit-subunit interactions
      between alpha-helices, we propose that Met-147, Ile-151, and Ile-158 lie on the
      same face of an alpha-helix that constitutes a dimerization interface. This
      alignment would also position Arg-140, Met-144, and Asp-154 on the same helical
      face. In support of the unusual positioning of a negatively charged residue at
      the dimer interface, we found that replacing Asp-154 with Ala repaired the
      defects caused by Ala substitutions of other residues located on the same helical
      face. These data also suggest that Asp-154 has an inhibitory effect on
      dimerization, which may be a key element in the control of FNR dimerization by
      O(2) availability.

PMID- 11581262
TI  - Isoforms of photosystem II antenna proteins in different plant species revealed
      by liquid chromatography-electrospray ionization mass spectrometry.
AB  - The high selectivity offered by reversed-phase high-performance liquid
      chromatography on-line coupled to electrospray ionization mass spectrometry has
      been utilized to characterize the major and minor light-harvesting proteins of
      photosystem II (Lhcb). Isomeric forms of the proteins, revealed either on the
      basis of different hydrophobicity enabling their chromatographic separation or on
      the basis of different molecular masses identified within one single
      chromatographic peak, were readily identified in a number of monocot and dicot
      species. The presence of several Lhcb1 isoforms (preferably in dicots) can
      explain the tendency of dicot Lhcb1 to form trimeric aggregates. The Lhcb1
      molecular masses ranged from 24,680 to 25,014 among different species, whereas
      within the same species, the isoforms differed by 14-280 mass units. All Lhcb1
      proteins appear to be highly conserved among different species such that they
      belong to a single gene group that has several different gene family members. In
      all species examined, the number of isoforms corresponded more or less to the
      genes cloned previously. Two isoforms of Lhcb3 were found in petunia and tomato.
      For Lhcb6, the most divergent of all light-harvesting proteins, the greatest
      number of isoforms was found in petunia, tobacco, tomato, and rice. Lhcb2, Lhcb4,
      and Lhcb5 were present in only one form. The isoforms are assumed to play an
      important role in the adaptation of plants to environmental changes.

PMID- 11581263
TI  - The ribosomal S6 kinases, cAMP-responsive element-binding, and STAT3 proteins are
      regulated by different leukemia inhibitory factor signaling pathways in mouse
      embryonic stem cells.
AB  - Mouse embryonic stem (ES) cells remain "pluripotent" in vitro in the continuous
      presence of leukemia inhibitory factor (LIF). In the absence of LIF, ES cells are
      irreversibly committed to differentiate into various lineages. In this study we
      have set up an in vitro assay based on the anti-apoptotic activity of LIF to
      distinguish pluripotent from "differentiation-committed" ES cells. We have
      examined the phosphorylation profiles of known (STAT3 and ERKs) and identified
      new (ribosomal S6 kinases (RSKs) and cAMP-responsive element-binding protein
      (CREB)) LIF-regulated targets in ES and in ES-derived neuronal cells. We have
      demonstrated that although STAT3, a crucial player in the maintenance of ES cell
      pluripotency, is induced by LIF in all cell types tested, the LIF-dependent
      activation of RSKs is restricted to ES cells. We have shown that LIF-induced
      phosphorylation of RSKs in ES cells is dependent on ERKs, whereas STAT3
      phosphorylation is not mediated by any known MAPK activities. Our results also
      demonstrate that the LIF-dependent phosphorylation of CREB is partially under the
      control of the RSK2 kinase.

PMID- 11581264
TI  - Mechanism of product chain length determination and the role of a flexible loop
      in Escherichia coli undecaprenyl-pyrophosphate synthase catalysis.
AB  - The Escherichia coli undecaprayl-pyrophosphate synthase (UPPs) structure has been
      solved using the single wavelength anomalous diffraction method. The putative
      substrate-binding site is located near the end of the betaA-strand with Asp-26
      playing a critical catalytic role. In both subunits, an elongated hydrophobic
      tunnel is found, surrounded by four beta-strands (betaA-betaB-betaD-betaC) and
      two helices (alpha2 and alpha3) and lined at the bottom with large residues Ile
      62, Leu-137, Val-105, and His-103. The product distributions formed by the use of
      the I62A, V105A, and H103A mutants are similar to those observed for wild-type
      UPPs. Catalysis by the L137A UPPs, on the other hand, results in predominantly
      the formation of the C(70) polymer rather than the C(55) polymer. Ala-69 and Ala
      143 are located near the top of the tunnel. In contrast to the A143V reaction,
      the C(30) intermediate is formed to a greater extent and is longer lived in the
      process catalyzed by the A69L mutant. These findings suggest that the small side
      chain of Ala-69 is required for rapid elongation to the C(55) product, whereas
      the large hydrophobic side chain of Leu-137 is required to limit the elongation
      to the C(55) product. The roles of residues located on a flexible loop were
      investigated. The S71A, N74A, or R77A mutants displayed 25-200-fold decrease in
      k(cat) values. W75A showed an 8-fold increase of the FPP K(m) value, and 22-33
      fold increases in the IPP K(m) values were observed for E81A and S71A. The loop
      may function to bridge the interaction of IPP with FPP, needed to initiate the
      condensation reaction and serve as a hinge to control the substrate binding and
      product release.

PMID- 11581265
TI  - Tetracycline-regulated gene expression mediated by a novel chimeric repressor
      that recruits histone deacetylases in mammalian cells.
AB  - Regulated gene expression will provide important platforms from which gene
      functions can be investigated and safer means of gene therapy may be developed.
      Histone deacetylases have recently been shown to play an important role in
      regulating gene expression. Here we investigated whether a more tightly
      controlled expression could be achieved by using a novel chimeric repressor that
      recruits histone deacetylases to a tetracycline-responsive promoter. This
      chimeric repressor was engineered by fusing the tetracycline repressor (TetR)
      with an mSin3-interacting domain of human Mad1 and was shown to bind the tetO(2)
      element with high affinity, and its binding was efficiently abrogated by
      doxycycline. The chimeric repressor was shown to directly interact with mSin3 of
      the histone deacetylase complex. This inducible system was further simplified by
      using a single vector that contained both a chimeric repressor expression
      cassette and a tetracycline-responsive promoter. When transiently introduced into
      mammalian cells, the chimeric repressor system exhibited a significantly lower
      basal level of luciferase activity (up to 25-fold) than that of the TetR control.
      When stably transfected into HEK 293 cells, the chimeric repressor system was
      shown to exert a tight control of green fluorescent protein expression in a
      doxycycline dose- and time-dependent fashion. Therefore, this novel chimeric
      repressor provides an effective means for more tightly regulated gene expression,
      and the simplified inducible system may be used for a broad range of basic and
      clinical studies.

PMID- 11581266
TI  - Characterization of drug transport by the human multidrug resistance protein 3
      (ABCC3).
AB  - We have characterized the substrate specificity and mechanism of transport of the
      human multidrug resistance-associated protein 3 (MRP3). A murine fibroblast-like
      cell line generated from the kidneys of mice that lack Mdr1a/b and Mrp1 was
      retrovirally transduced with MRP3 cDNA. Stable clones overproducing MRP3 were
      resistant to the epipodophyllotoxins etoposide and teniposide but not to
      vincristine, doxorubicin, and cisplatin, drugs suggested to be MRP3 substrates by
      others. The resistance to etoposide was associated with reduced cellular
      accumulation and enhanced efflux of this drug and was not affected by depleting
      cells of glutathione but was inhibited by several common organic anion transport
      inhibitors. Membrane vesicles from infected insect cells expressing MRP3 mediated
      ATP-dependent transport of estradiol 17-beta-D-glucuronide, leukotriene C(4),
      dinitrophenyl S-glutathione but not glutathione itself, and etoposide
      glucuronide, a major metabolite of etoposide in vivo. The transport of estradiol
      17-beta-D-glucuronide by MRP3 was inhibited in a concentration-dependent manner
      by both etoposide and methotrexate. Even though etoposide glucuronide is an
      excellent substrate for MRP3, this compound is not involved in the etoposide
      resistance of our MRP3 cells, as these cells extrude unmodified etoposide rather
      than etoposide glucuronide.

PMID- 11581267
TI  - Synthetic activity of Sso DNA polymerase Y1, an archaeal DinB-like DNA
      polymerase, is stimulated by processivity factors proliferating cell nuclear
      antigen and replication factor C.
AB  - DNA replication efficiency is dictated by DNA polymerases (pol) and their
      associated proteins. The recent discovery of DNA polymerase Y family
      (DinB/UmuC/RAD30/REV1 superfamily) raises a question of whether the DNA
      polymerase activities are modified by accessory proteins such as proliferating
      cell nuclear antigen (PCNA). In fact, the activity of DNA pol IV (DinB) of
      Escherichia coli is enhanced upon interaction with the beta subunit, the
      processivity factor of DNA pol III. Here, we report the activity of Sso DNA pol
      Y1 encoded by the dbh gene of the archaeon Sulfolobus solfataricus is greatly
      enhanced by the presence of PCNA and replication factor C (RFC). Sso pol Y1 per
      se was a distributive enzyme but a substantial increase in the processivity was
      observed on poly(dA)-oligo(dT) in the presence of PCNA (039p or 048p) and RFC.
      The length of the synthesized DNA product reached at least 200 nucleotides. Sso
      pol Y1 displayed a higher affinity for DNA compared with pol IV of E. coli,
      suggesting that the two DNA polymerases have distinct reason(s) to require the
      processivity factors for efficient DNA synthesis. The abilities of pol Y1 and pol
      IV to bypass DNA lesions and their sensitive sites to protease are also
      discussed.

PMID- 11581268
TI  - Activity of recombinant dengue 2 virus NS3 protease in the presence of a
      truncated NS2B co-factor, small peptide substrates, and inhibitors.
AB  - Recombinant forms of the dengue 2 virus NS3 protease linked to a 40-residue co
      factor, corresponding to part of NS2B, have been expressed in Escherichia coli
      and shown to be active against para-nitroanilide substrates comprising the P6-P1
      residues of four substrate cleavage sequences. The enzyme is inactive alone or
      after the addition of a putative 13-residue co-factor peptide but is active when
      fused to the 40-residue co-factor, by either a cleavable or a noncleavable
      glycine linker. The NS4B/NS5 cleavage site was processed most readily, with
      optimal processing conditions being pH 9, I = 10 mm, 1 mm CHAPS, 20% glycerol. A
      longer 10-residue peptide corresponding to the NS2B/NS3 cleavage site (P6-P4')
      was a poorer substrate than the hexapeptide (P6-P1) para-nitroanilide substrate
      under these conditions, suggesting that the prime side substrate residues did not
      contribute significantly to protease binding. We also report the first inhibitors
      of a co-factor-complexed, catalytically active flavivirus NS3 protease. Aprotinin
      was the only standard serine protease inhibitor to be active, whereas a number of
      peptide substrate analogues were found to be competitive inhibitors at micromolar
      concentrations.

PMID- 11581269
TI  - Polycystin-1 interacts with intermediate filaments.
AB  - Polycystin-1, the protein defective in a majority of patients with autosomal
      dominant polycystic kidney disease, is a ubiquitously expressed multi-span
      transmembrane protein of unknown function. Subcellular localization studies found
      this protein to be a component of various cell junctional complexes and to be
      associated with the cytoskeleton, but the specificity and nature of such
      associations are not known. To identify proteins that interact with the
      polycystin-1 C-tail (P1CT), this segment was used as bait in a yeast two-hybrid
      screening of a kidney epithelial cell library. The intermediate filament (IF)
      protein vimentin was identified as a strong polycystin-1-interacting partner.
      Cytokeratins K8 and K18 and desmin were also found to interact with P1CT. These
      interactions were mediated by coiled-coil motifs in polycystin-1 and IF proteins.
      Vimentin, cytokeratins K8 and K18, and desmin also bound directly to P1CT in GST
      pull-down and in in vitro filament assembly assays. Two observations confirmed
      these interactions in vivo: (i) a cell membrane-anchored form of recombinant P1CT
      decorated the IF network and was found to associate with the cytoskeleton in
      detergent-solubilized cells and (ii) endogenous polycystin-1 distributed with IF
      at desmosomal junctions. Polycystin-1 may utilize this association for
      structural, storage, or signaling functions.

PMID- 11581270
TI  - The Cockayne Syndrome group B gene product is involved in general genome base
      excision repair of 8-hydroxyguanine in DNA.
AB  - Cockayne Syndrome (CS) is a human genetic disorder with two complementation
      groups, CS-A and CS-B. The CSB gene product is involved in transcription-coupled
      repair of DNA damage but may participate in other pathways of DNA metabolism. The
      present study investigated the role of different conserved helicase motifs of CSB
      in base excision repair. Stably transformed human cell lines with site-directed
      CSB mutations in different motifs within its putative helicase domain were
      established. We find that CSB null and helicase motif V and VI mutants had
      greater sensitivity than wild type cells to gamma-radiation. Whole cell extracts
      from CSB null and motif V/VI mutants had lower activity of 8-hydroxyguanine
      incision in DNA than wild type cells. Also, 8-hydroxyguanine accumulated more in
      CSB null and motif VI mutant cells than in wild type cells after exposure to
      gamma-radiation. We conclude that a deficiency in general genome base excision
      repair of selective modified DNA base(s) might contribute to CS pathogenesis.
      Furthermore, whereas the disruption of helicase motifs V or VI results in a CSB
      phenotype, mutations in other helicase motifs do not cause this effect. The
      biological functions of CSB in different DNA repair pathways may be mediated by
      distinct functional motifs of the protein.

PMID- 11581271
TI  - Functional analysis of conserved residues in the putative "finger" domain of
      telomerase reverse transcriptase.
AB  - Telomerase is a ribonucleoprotein reverse transcriptase (RT) responsible for the
      maintenance of one strand of telomere terminal repeats. The catalytic protein
      subunit of telomerase, known generically as telomerase reverse transcriptase
      (TERT), exhibits significant homology to RTs encoded by retroviruses and
      retroelements. The polymerization mechanisms of telomerase may therefore be
      similar to those of the "conventional" RTs. In this study, we explored the extent
      of mechanistic conservation by analyzing mutations of conserved residues within
      the putative "finger" domain of TERT. Previous analysis has implicated this
      domain of retroviral RTs in nucleotide and RNA binding and in processivity
      control. Our results demonstrate that residues conserved between TERT and human
      immunodeficiency virus-1 RT are more likely than TERT-specific residues to be
      required for enzyme activity. In addition, residues presumed to make direct
      contact with either the RNA or nucleotide substrate appear to be functionally
      more important. Furthermore, distinct biochemical defects can be observed for
      alterations in the putative RNA- and nucleotide-binding TERT residues in a manner
      that can be rationalized by their postulated mechanisms of action. This study
      thus supports a high degree of mechanistic conservation between telomerase and
      retroviral RTs and underscores the roles of distinct aspects of telomerase
      biochemistry in telomere length maintenance.

PMID- 11581272
TI  - Thermodynamics and kinetics of Hsp70 association with A + U-rich mRNA
      destabilizing sequences.
AB  - Rapid mRNA degradation directed by A + U-rich elements (AREs) is mediated by the
      interaction of specific RNA-binding proteins to these sequences. The protein
      chaperone Hsp70 has been identified in a cellular complex containing the ARE
      binding protein AUF1 and has also been detected in direct contact with A + U-rich
      RNA substrates, indicating that Hsp70 may be involved in the regulation of ARE
      directed mRNA turnover. By using gel mobility shift and fluorescence anisotropy
      assays, we have determined that Hsp70 directly and specifically associates with U
      rich RNA substrates in solution. With the ARE from tumor necrosis factor alpha
      (TNFalpha) mRNA, Hsp70 forms a dynamic complex consistent with a 1:1 association
      of protein:RNA but demonstrates cooperative binding behavior on polyuridylate
      substrates. Unlike AUF1, the RNA binding activity of Hsp70 is not regulated by
      ion-dependent folding of the TNFalpha ARE, suggesting that AUF1 and Hsp70
      recognize distinct binding determinants on this RNA substrate. Binding of Hsp70
      to the TNFalpha ARE is driven entirely by enthalpy at physiological temperatures,
      indicating that burial of hydrophobic surfaces is likely the principal mechanism
      stabilizing the Hsp70.RNA complex. Potential roles for the interaction of Hsp70
      with ARE-containing mRNAs in the regulation of mRNA turnover and/or translational
      efficiency are discussed.

PMID- 11581273
TI  - Direct interaction with contactin targets voltage-gated sodium channel
      Na(v)1.9/NaN to the cell membrane.
AB  - The mechanisms that target various sodium channels within different regions of
      the neuronal membrane, which they endow with different physiological properties,
      are not yet understood. To examine this issue we studied the voltage-gated sodium
      channel Na(v)1.9/NaN, which is preferentially expressed in small sensory neurons
      of dorsal root ganglia and trigeminal ganglia and the nonmyelinated axons that
      arise from them. Our results show that the cell adhesion molecule contactin binds
      directly to Na(v)1.9/NaN and recruits tenascin to the protein complex in vitro.
      Na(v)1.9/NaN and contactin co-immunoprecipitate from dorsal root ganglia and
      transfected Chinese hamster ovary cell line, and co-localize in the C-type neuron
      soma and along nonmyelinated C-fibers and at nerve endings in the skin. Co
      transfection of Chinese hamster ovary cells with Na(v)1.9/NaN and contactin
      enhances the surface expression of the sodium channel over that of Na(v)1.9/NaN
      alone. Thus contactin binds directly to Na(v)1.9/NaN and participates in the
      surface localization of this channel along nonmyelinated axons.

PMID- 11581274
TI  - Gonadotropin-releasing hormone receptor-coupled gene network organization.
AB  - An early gene cDNA microarray was developed to study genes that are regulated
      immediately following gonadotropin-releasing hormone (GnRH) receptor activation.
      956 selected candidate genes were printed in triplicate, a t statistic-based
      regulation algorithm was used for data analysis, and the response to GnRH in a
      time course from 1 to 6 h was determined. Measurements were highly reproducible
      within arrays, between arrays, and between experiments. Accuracy and algorithm
      reliability were established by real-time polymerase chain reaction assays of 60
      genes. Gene changes ranging from 1.3- to 31-fold on the microarray were confirmed
      by real-time polymerase chain reaction. Many of the genes were found to be highly
      regulated. The regulated genes identified were all elevated at 1 h of treatment
      and returned nearly or completely to baseline levels of expression by 3 h of
      treatment. This broad, robust, and transient transcriptional response to constant
      GnRH exposure includes modulators of signal transduction (e.g. Rgs2 and IkappaB),
      cytoskeletal proteins (e.g. gamma-actin), and transcription factors (e.g. c-Fos,
      Egr1, and LRG21). The interplay of the activators, repressors, and feedback
      inhibitors identified embodies a combinatorial code to direct the activity of
      specific downstream secondary genes.

PMID- 11581275
TI  - The anti-inflammatory cytokine, interleukin (IL)-10, blocks the inhibitory effect
      of IL-1 beta on long term potentiation. A role for JNK.
AB  - Several effects of the proinflammatory cytokine, interleukin-1 beta (IL-1 beta),
      have been described in the central nervous system, and one area of the brain
      where marked changes have been reported is the hippocampus. Among these changes
      are an IL-1 beta-induced inhibition of long term potentiation (LTP) in perforant
      path-granule cell synapses and an attenuation of glutamate release in
      synaptosomes prepared from the hippocampus. Evidence suggests that, at least in
      circulating cells, the anti-inflammatory cytokine, IL-10, antagonizes certain
      effects of IL-1. We investigated the effect of IL-10 on IL-1 beta-induced
      inhibition of LTP and glutamate release. The evidence presented indicates that IL
      1 beta stimulates the stress-activated protein kinase, c-Jun-activated protein
      kinase (JNK), and IL-1 receptor-associated kinase, which may explain its
      inhibitory effect on release and LTP, and that IL-10 reversed the IL-1 beta
      induced stimulation of JNK activity and inhibition of release and LTP. We
      observed that IL-10 abrogated the stimulatory effect of IL-1 beta on superoxide
      dismutase activity and reactive oxygen species production, whereas the H(2)O(2)
      induced inhibition of LTP was also blocked by IL-10. We present evidence that
      suggests that the action of IL-10 may be mediated by its ability to induce
      shedding of the IL-1 type I receptor.

PMID- 11581276
TI  - Chromodomain protein Swi6-mediated role of DNA polymerase alpha in establishment
      of silencing in fission Yeast.
AB  - Although DNA replication has been thought to play an important role in the
      silencing of mating type loci in Saccharomyces cerevisiae, recent studies
      indicate that silencing can be decoupled from replication. In Schizosaccharomyces
      pombe, mating type silencing is brought about by the trans-acting proteins,
      namely Swi6, Clr1-Clr4, and Rhp6, in cooperation with the cis-acting silencers.
      The latter contain an autonomous replication sequence, suggesting that DNA
      replication may be critical for silencing in S. pombe. To investigate the
      connection between DNA replication and silencing in S. pombe, we analyzed several
      temperature-sensitive mutants of DNA polymerase alpha. We find that one such
      mutant, swi7H4, exhibits silencing defects at mat, centromere, and telomere loci.
      This effect is independent of the checkpoint and replication defects of the
      mutant. Interestingly, the extent of the silencing defect in the swi7H4 mutant at
      the silent mat2 locus is further enhanced in absence of the cis-acting,
      centromere-proximal silencer. The chromodomain protein Swi6, which is required
      for silencing and is localized to mat and other heterochromatin loci, interacts
      with DNA polymerase alpha in vivo and in vitro in wild type cells. However, it
      does not interact with the mutant pol alpha and is delocalized away from the
      silent mat loci in the mutant. Our results demonstrate a role of DNA polymerase
      alpha in the establishment of silencing. We propose a recruitment model for the
      coupling of DNA replication with the establishment of silencing by the
      chromodomain protein Swi6, which may be applicable to higher eukaryotes.

PMID- 11581282
TI  - Phosphoinositides and phagocytosis.
AB  - Phosphoinositide 3 kinases (PI3Ks)*Abbreviation used in this paper: PI3K,
      phosphoinositide 3 kinase. are known as regulators of phagocytosis. Recent
      results demonstrate that class I and III PI3Ks act consecutively in phagosome
      formation and maturation, and that their respective products,
      phosphatidylinositol 3,4,5-trisphosphate (PI[3,4,5]P(3)) and phosphatidylinositol
      3-phosphate (PI[3]P), accumulate transiently at different stages. Phagosomes
      containing Mycobacterium tuberculosis do not acquire the PI(3)P-binding protein
      EEA1, which is required for phagosome maturation. This suggests a possible
      mechanism of how this microorganism evades degradation in phagolysosomes.

PMID- 11581283
TI  - Distinct roles of class I and class III phosphatidylinositol 3-kinases in
      phagosome formation and maturation.
AB  - Phagosomes acquire their microbicidal properties by fusion with lysosomes.
      Products of phosphatidylinositol 3-kinase (PI 3-kinase) are required for
      phagosome formation, but their role in maturation is unknown. Using chimeric
      fluorescent proteins encoding tandem FYVE domains, we found that
      phosphatidylinositol 3-phosphate (PI[3]P) accumulates greatly but transiently on
      the phagosomal membrane. Unlike the 3'-phosphoinositides generated by class I PI
      3-kinases which are evident in the nascent phagosomal cup, PI(3)P is only
      detectable after the phagosome has sealed. The class III PI 3-kinase VPS34 was
      found to be responsible for PI(3)P synthesis and essential for phagolysosome
      formation. In contrast, selective ablation of class I PI 3-kinase revealed that
      optimal phagocytosis, but not maturation, requires this type of enzyme. These
      results highlight the differential functional role of the two families of
      kinases, and raise the possibility that PI(3)P production by VPS34 may be
      targeted during the maturation arrest induced by some intracellular parasites.

PMID- 11581284
TI  - Activity-dependent nuclear translocation and intranuclear distribution of NFATc
      in adult skeletal muscle fibers.
AB  - TTranscription factor nuclear factor of activated T cells NFATc (NFATc1, NFAT2)
      may contribute to slow-twitch skeletal muscle fiber type-specific gene
      expression. Green fluorescence protein (GFP) or FLAG fusion proteins of either
      wild-type or constitutively active mutant NFATc [NFATc(S-->A)] were expressed in
      cultured adult mouse skeletal muscle fibers from flexor digitorum brevis
      (predominantly fast-twitch). Unstimulated fibers expressing NFATc(S-->A)
      exhibited a distinct intranuclear pattern of NFATc foci. In unstimulated fibers
      expressing NFATc-GFP, fluorescence was localized at the sarcomeric z-lines and
      absent from nuclei. Electrical stimulation using activity patterns typical of
      slow-twitch muscle, either continuously at 10 Hz or in 5-s trains at 10 Hz every
      50 s, caused cyclosporin A-sensitive appearance of fluorescent foci of NFATc-GFP
      in all nuclei. Fluorescence of nuclear foci increased during the first hour of
      stimulation and then remained constant during a second hour of stimulation.
      Kinase inhibitors and ionomycin caused appearance of nuclear foci of NFATc-GFP
      without electrical stimulation. Nuclear translocation of NFATc-GFP did not occur
      with either continuous 1 Hz stimulation or with the fast-twitch fiber activity
      pattern of 0.1-s trains at 50 Hz every 50 s. The stimulation pattern-dependent
      nuclear translocation of NFATc demonstrated here could thus contribute to fast
      twitch to slow-twitch fiber type transformation.

PMID- 11581286
TI  - Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic
      outgrowth, and microtubule organization.
AB  - MAP1B and MAP2 are major members of neuronal microtubule-associated proteins
      (MAPs). To gain insights into the function of MAP2 in vivo, we generated MAP2
      deficient (map2(-/-)) mice. They developed without any apparent abnormalities,
      which indicates that MAP2 is dispensable in mouse survival. Because previous
      reports suggest a functional redundancy among MAPs, we next generated mice
      lacking both MAP2 and MAP1B to test their possible synergistic functions in vivo.
      Map2(-/-)map1b(-/-) mice died in their perinatal period. They showed not only
      fiber tract malformations but also disrupted cortical patterning caused by
      retarded neuronal migration. In spite of this, their cortical layer maintained an
      "inside-out" pattern. Detailed observation of primary cultures of hippocampal
      neurons from map2(-/-)map1b(-/-) mice revealed inhibited microtubule bundling and
      neurite elongation. In these neurons, synergistic effects caused by the loss of
      MAP2 and MAP1B were more apparent in dendrites than in axons. The spacing of
      microtubules was reduced significantly in map2(-/-)map1b(-/-) mice in vitro and
      in vivo. These results suggest that MAP2 and MAP1B have overlapping functions in
      neuronal migration and neurite outgrowth by organizing microtubules in developing
      neurons both for axonal and dendritic morphogenesis but more dominantly for
      dendritic morphogenesis.

PMID- 11581285
TI  - Reorganization of multivesicular bodies regulates MHC class II antigen
      presentation by dendritic cells.
AB  - Immature dendritic cells (DCs) sample their environment for antigens and after
      stimulation present peptide associated with major histocompatibility complex
      class II (MHC II) to naive T cells. We have studied the intracellular trafficking
      of MHC II in cultured DCs. In immature cells, the majority of MHC II was stored
      intracellularly at the internal vesicles of multivesicular bodies (MVBs). In
      contrast, DM, an accessory molecule required for peptide loading, was located
      predominantly at the limiting membrane of MVBs. After stimulation, the internal
      vesicles carrying MHC II were transferred to the limiting membrane of the MVB,
      bringing MHC II and DM to the same membrane domain. Concomitantly, the MVBs
      transformed into long tubular organelles that extended into the periphery of the
      cells. Vesicles that were formed at the tips of these tubules nonselectively
      incorporated MHC II and DM and presumably mediated transport to the plasma
      membrane. We propose that in maturing DCs, the reorganization of MVBs is
      fundamental for the timing of MHC II antigen loading and transport to the plasma
      membrane.

PMID- 11581287
TI  - KIFC3, a microtubule minus end-directed motor for the apical transport of annexin
      XIIIb-associated Triton-insoluble membranes.
AB  - We have identified and characterized a COOH-terminal motor domain-type kinesin
      superfamily protein (KIFC), KIFC3, in the kidney. KIFC3 is a minus end-directed
      microtubule motor protein, therefore it accumulates in regions where minus ends
      of microtubules assemble. In polarized epithelial cells, KIFC3 is localized on
      membrane organelles immediately beneath the apical plasma membrane of renal
      tubular epithelial cells in vivo and polarized MDCK II cells in vitro. Flotation
      assay, coupled with detergent extraction, demonstrated that KIFC3 is associated
      with Triton X-100-insoluble membrane organelles, and that it overlaps with
      apically transported TGN-derived vesicles. This was confirmed by
      immunoprecipitation and by GST pulldown experiments showing the specific
      colocalization of KIFC3 and annexin XIIIb, a previously characterized membrane
      protein for apically transported vesicles (Lafont, F., S. Lecat, P. Verkade, and
      K. Simons. 1998. J. Cell Biol. 142:1413-1427). Furthermore, we proved that the
      apical transport of both influenza hemagglutinin and annexin XIIIb was partially
      inhibited or accelerated by overexpression of motor-domainless (dominant
      negative) or full-length KIFC3, respectively. Absence of cytoplasmic dynein on
      these annexin XIIIb-associated vesicles and distinct distribution of the two
      motors on the EM level verified the existence of KIFC3-driven transport in
      epithelial cells.

PMID- 11581288
TI  - Pivotal role of VASP in Arp2/3 complex-mediated actin nucleation, actin branch
      formation, and Listeria monocytogenes motility.
AB  - The Listeria monocytogenes ActA protein mediates actin-based motility by
      recruiting and stimulating the Arp2/3 complex. In vitro, the actin monomer
      binding region of ActA is critical for stimulating Arp2/3-dependent actin
      nucleation; however, this region is dispensable for actin-based motility in
      cells. Here, we provide genetic and biochemical evidence that vasodilator
      stimulated phosphoprotein (VASP) recruitment by ActA can bypass defects in actin
      monomer-binding. Furthermore, purified VASP enhances the actin-nucleating
      activity of wild-type ActA and the Arp2/3 complex while also reducing the
      frequency of actin branch formation. These data suggest that ActA stimulates the
      Arp2/3 complex by both VASP-dependent and -independent mechanisms that generate
      distinct populations of actin filaments in the comet tails of L. monocytogenes.
      The ability of VASP to contribute to actin filament nucleation and to regulate
      actin filament architecture highlights the central role of VASP in actin-based
      motility.

PMID- 11581289
TI  - A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice.
AB  - Dystrophin-deficient muscles experience large reductions in expression of nitric
      oxide synthase (NOS), which suggests that NO deficiency may influence the
      dystrophic pathology. Because NO can function as an antiinflammatory and
      cytoprotective molecule, we propose that the loss of NOS from dystrophic muscle
      exacerbates muscle inflammation and fiber damage by inflammatory cells. Analysis
      of transgenic mdx mice that were null mutants for dystrophin, but expressed
      normal levels of NO in muscle, showed that the normalization of NO production
      caused large reductions in macrophage concentrations in the mdx muscle.
      Expression of the NOS transgene in mdx muscle also prevented the majority of
      muscle membrane injury that is detectable in vivo, and resulted in large
      decreases in serum creatine kinase concentrations. Furthermore, our data show
      that mdx muscle macrophages are cytolytic at concentrations that occur in
      dystrophic, NOS-deficient muscle, but are not cytolytic at concentrations that
      occur in dystrophic mice that express the NOS transgene in muscle. Finally, our
      data show that antibody depletions of macrophages from mdx mice cause significant
      reductions in muscle membrane injury. Together, these findings indicate that
      macrophages promote injury of dystrophin-deficient muscle, and the loss of normal
      levels of NO production by dystrophic muscle exacerbates inflammation and
      membrane injury in muscular dystrophy.

PMID- 11581290
TI  - Activation of ErbB2 receptor tyrosine kinase supports invasion of endothelial
      cells by Neisseria meningitidis.
AB  - ErbB2 is a receptor tyrosine kinase belonging to the family of epidermal growth
      factor (EGF) receptors which is generally involved in cell differentiation,
      proliferation, and tumor growth, and activated by heterodimerization with the
      other members of the family. We show here that type IV pilus-mediated adhesion of
      Neisseria meningitidis onto endothelial cells induces tyrosyl phosphorylation and
      massive recruitment of ErbB2 underneath the bacterial colonies. However, neither
      the phosphorylation status nor the cellular localization of the EGF receptors,
      ErbB3 or ErbB4, were affected in infected cells. ErbB2 phosphorylation induced by
      N. meningitidis provides docking sites for the kinase src and leads to its
      subsequent activation. Specific inhibition of either ErbB2 and/or src activity
      reduces bacterial internalization into endothelial cells without affecting
      bacteria-induced actin cytoskeleton reorganization or ErbB2 recruitment.
      Moreover, inhibition of both actin polymerization and the ErbB2/src pathway
      totally prevents bacterial entry. Altogether, our results provide new insight
      into ErbB2 function by bringing evidence of a bacteria-induced ErbB2 clustering
      leading to src kinase phosphorylation and activation. This pathway, in
      cooperation with the bacteria-induced reorganization of the actin cytoskeleton,
      is required for the efficient internalization of N. meningitidis into endothelial
      cells, an essential process enabling this pathogen to cross host cell barriers.

PMID- 11581291
TI  - Cytoplasmic anchorage of L-selectin controls leukocyte capture and rolling by
      increasing the mechanical stability of the selectin tether.
AB  - L-selectin is a leukocyte lectin that mediates leukocyte capture and rolling in
      the vasculature. The cytoplasmic domain of L-selectin has been shown to regulate
      leukocyte rolling. In this study, the regulatory mechanisms by which this domain
      controls L-selectin adhesiveness were investigated. We report that an L-selectin
      mutant generated by truncation of the COOH-terminal 11 residues of L-selectin
      tail, which impairs association with the cytoskeletal protein alpha-actinin,
      could capture leukocytes to glycoprotein L-selectin ligands under physiological
      shear flow. However, the conversion of initial tethers into rolling was impaired
      by this partial tail truncation, and was completely abolished by a further four
      residue truncation of the L-selectin tail. Physical anchorage of both cell-free
      tail-truncated mutants within a substrate fully rescued their adhesive
      deficiencies. Microkinetic analysis of full-length and truncated L-selectin
      mediated rolling at millisecond temporal resolution suggests that the lifetime of
      unstressed L-selectin tethers is unaffected by cytoplasmic tail truncation.
      However, cytoskeletal anchorage of L-selectin stabilizes the selectin tether by
      reducing the sensitivity of its dissociation rate to increasing shear forces. Low
      force sensitivity (reactive compliance) of tether lifetime is crucial for
      selectins to mediate leukocyte rolling under physiological shear stresses. This
      is the first demonstration that reduced reactive compliance of L-selectin tethers
      is regulated by cytoskeletal anchorage, in addition to intrinsic mechanical
      properties of the selectin-carbohydrate bond.

PMID- 11581292
TI  - Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes
      osteopenia with multiple fractures.
AB  - Targeted disruption of core binding factor alpha1 (Cbfa1) showed that Cbfa1 is an
      essential transcription factor in osteoblast differentiation and bone formation.
      Furthermore, both in vitro and in vivo studies showed that Cbfa1 plays important
      roles in matrix production and mineralization. However, it remains to be
      clarified how Cbfa1 controls osteoblast differentiation, bone formation, and bone
      remodelling. To understand fully the physiological functions of Cbfa1, we
      generated transgenic mice that overexpressed Cbfa1 in osteoblasts using type I
      collagen promoter. Unexpectedly, Cbfa1 transgenic mice showed osteopenia with
      multiple fractures. Cortical bone, which was thin, porous, and enriched with
      osteopontin, was invaded by osteoclasts, despite the absence of acceleration of
      osteoclastogenesis. Although the number of neonatal osteoblasts was increased,
      their function was impaired in matrix production and mineralization. Furthermore,
      terminally differentiated osteoblasts, which strongly express osteocalcin, and
      osteocytes were diminished greatly, whereas less mature osteoblasts expressing
      osteopontin accumulated in adult bone. These data indicate that immature
      organization of cortical bone, which was caused by the maturational blockage of
      osteoblasts, led to osteopenia and fragility in transgenic mice, demonstrating
      that Cbfa1 inhibits osteoblast differentiation at a late stage.

PMID- 11581293
TI  - Challenges to achieving clinical transplantation tolerance.

PMID- 11581294
TI  - The multiligand receptor RAGE as a progression factor amplifying immune and
      inflammatory responses.

PMID- 11581295
TI  - Phagocyte receptors for apoptotic cells: recognition, uptake, and consequences.

PMID- 11581296
TI  - Progress in the search for neuronal mechanisms coupling type 2 diabetes to
      obesity.

PMID- 11581297
TI  - The Survivin saga goes in vivo.

PMID- 11581298
TI  - Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor
      ligand specificity.
AB  - RANK, the receptor activator of NF-kappaB, and its ligand RANKL (initially termed
      TRANCE, also termed ODF and OPGL), are a TNF superfamily receptor-ligand pair
      that govern the development and function of osteoclasts, lymphoid tissue, and
      mammary epithelium. While TNF family cytokines share a common structural
      scaffold, individual receptor-ligand pairs associate with high specificity. Given
      the low level of amino acid conservation among members of the TNF superfamily,
      the means by which these molecules achieve specificity cannot be completely
      understood without knowledge of their three-dimensional structures. To determine
      the elements of RANKL that mediate RANK activation, we have crystallized the
      ectodomain of murine RANKL and solved its structure to a resolution of 2.6 A.
      RANKL self-associates as a homotrimer with four unique surface loops that
      distinguish it from other TNF family cytokines. Mutagenesis of selected residues
      in these loops significantly modulates RANK activation, as evidenced by in vitro
      osteoclastogenesis, thereby establishing their necessity in mediating the
      biological activities of RANKL. Such structural determinants of RANKL-RANK
      specificity may be of relevance in the pharmacologic design of compounds to
      ameliorate osteopenic disorders of bone.

PMID- 11581299
TI  - Cancer gene therapy using a survivin mutant adenovirus.
AB  - We have constructed a replication-deficient adenovirus encoding a
      nonphosphorylatable Thr(34)-->Ala mutant of the apoptosis inhibitor survivin (pAd
      T34A) to target tumor cell viability in vitro and in vivo. Infection with pAd
      T34A caused spontaneous apoptosis in cell lines of breast, cervical, prostate,
      lung, and colorectal cancer. In contrast, pAd-T34A did not affect cell viability
      of proliferating normal human cells, including fibroblasts, endothelium, or
      smooth muscle cells. Infection of tumor cells with pAd-T34A resulted in
      cytochrome c release from mitochondria, cleavage of approximately 46-kDa upstream
      caspase-9, processing of caspase-3 to the active subunits of approximately 17 and
      19 kDa, and increased caspase-3 catalytic activity. When compared with
      chemotherapeutic regimens, pAd-T34A was as effective as taxol and considerably
      more effective than adriamycin in induction of tumor cell apoptosis and enhanced
      taxol-induced cell death. In three xenograft breast cancer models in
      immunodeficient mice, pAd-T34A suppressed de novo tumor formation, inhibited by
      approximately 40% the growth of established tumors, and reduced intraperitoneal
      tumor dissemination. Tumors injected with pAd-T34A exhibited loss of
      proliferating cells and massive apoptosis by in situ internucleosomal DNA
      fragmentation. These data suggest that adenoviral targeting of the survivin
      pathway may provide a novel approach for selective cancer gene therapy.

PMID- 11581300
TI  - Transgenic expression of survivin in keratinocytes counteracts UVB-induced
      apoptosis and cooperates with loss of p53.
AB  - The inhibitor of apoptosis protein survivin has been implicated in both cell
      cycle control and apoptosis resistance. To discriminate between these different
      roles, we used transgenic expression of survivin in the skin as a model for cell
      proliferation, differentiation, and apoptosis. Transgenic mice expressing
      survivin under the control of a keratin-14 promoter developed normally, without
      histologic abnormalities of the skin or hair, epidermal hyperplasia, or
      developmental abnormalities of basal or suprabasal epidermis. Keratinocyte
      proliferation assessed under basal conditions, or after ultraviolet-B (UVB)
      irradiation, or phorbol ester stimulation was unchanged in survivin transgenic
      mice. In contrast, survivin expression inhibited UVB-induced apoptosis in vitro
      and in vivo (i.e., sunburn cell formation), whereas it did not affect Fas-induced
      cell death. When crossed with p53 knockout mice, transgenic expression of
      survivin in a p53(+/-) background substituted for the loss of a second p53 allele
      and further inhibited UVB-induced apoptosis. These data provide the first in vivo
      evidence that survivin inhibits apoptosis and suggest that this pathway may
      oppose the elimination of cancerous cells by p53.

PMID- 11581302
TI  - Requirement for the L-type Ca(2+) channel alpha(1D) subunit in postnatal
      pancreatic beta cell generation.
AB  - Pancreatic beta cells are the source of insulin, which directly lowers blood
      glucose levels in the body. Our analyses of alpha(1D) gene-knockout (alpha(1D)(-/
      )) mice show that the L-type calcium channel, alpha(1D), is required for proper
      beta cell generation in the postnatal pancreas. Knockout mice were
      characteristically slightly smaller than their littermates and exhibited
      hypoinsulinemia and glucose intolerance. However, isolated alpha(1D)(-/-) islets
      persisted in glucose sensing and insulin secretion, with compensatory
      overexpression of another L-type channel gene, alpha(1C). Histologically, newborn
      alpha(1D)(-/-) mice had an equivalent number of islets to wild-type mice. In
      contrast, adult alpha(1D)(-/-) mice showed a decrease in the number and size of
      islets, compared with littermate wild-type mice due to a decrease in beta cell
      generation. TUNEL staining showed that there was no increase in cell death in
      alpha(1D)(-/-) islets, and a 5-bromo-2' deoxyuridine-labeling (BrdU-labeling)
      assay illustrated significant reduction in the proliferation rate of beta cells
      in alpha(1D)(-/-) islets.

PMID- 11581301
TI  - Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2
      diabetes.
AB  - PPARgamma is a ligand-activated transcription factor and functions as a
      heterodimer with a retinoid X receptor (RXR). Supraphysiological activation of
      PPARgamma by thiazolidinediones can reduce insulin resistance and hyperglycemia
      in type 2 diabetes, but these drugs can also cause weight gain. Quite
      unexpectedly, a moderate reduction of PPARgamma activity observed in heterozygous
      PPARgamma-deficient mice or the Pro12Ala polymorphism in human PPARgamma, has
      been shown to prevent insulin resistance and obesity induced by a high-fat diet.
      In this study, we investigated whether functional antagonism toward PPARgamma/RXR
      could be used to treat obesity and type 2 diabetes. We show herein that an RXR
      antagonist and a PPARgamma antagonist decrease triglyceride (TG) content in white
      adipose tissue, skeletal muscle, and liver. These inhibitors potentiated leptin's
      effects and increased fatty acid combustion and energy dissipation, thereby
      ameliorating HF diet-induced obesity and insulin resistance. Paradoxically,
      treatment of heterozygous PPARgamma-deficient mice with an RXR antagonist or a
      PPARgamma antagonist depletes white adipose tissue and markedly decreases leptin
      levels and energy dissipation, which increases TG content in skeletal muscle and
      the liver, thereby leading to the re-emergence of insulin resistance. Our data
      suggested that appropriate functional antagonism of PPARgamma/RXR may be a
      logical approach to protection against obesity and related diseases such as type
      2 diabetes.

PMID- 11581303
TI  - Mitochondrial coupling factor 6 as a potent endogenous vasoconstrictor.
AB  - We demonstrated recently that coupling factor 6, an essential component of the
      energy-transducing stalk of mitochondrial ATP synthase, suppresses the synthesis
      of prostacyclin in vascular endothelial cells. Here, we tested the hypothesis
      that coupling factor 6 is present on the cell surface and is involved in the
      regulation of systemic circulation. This peptide is present on the surface of CRL
      2222 vascular endothelial cells and is released by these cells into the medium.
      In vivo, the peptide circulates in the vascular system of the rat, and its gene
      expression and plasma concentration are higher in spontaneously hypertensive rats
      (SHRs) than in normotensive controls. Elevation of blood pressure with
      norepinephrine did not affect the plasma concentration of coupling factor 6.
      Intravenous injection of recombinant peptide increased blood pressure, apparently
      by suppressing prostacyclin synthesis, whereas a specific Ab to coupling factor 6
      decreased systemic blood pressure concomitantly with an increase in plasma
      prostacyclin. Interestingly, the antibody's hypotensive effect could be abolished
      by treating with the cyclooxygenase inhibitor indomethacin. These findings
      indicate that mitochondrial coupling factor 6 functions as a potent endogenous
      vasoconstrictor in the fashion of a circulating hormone and may suggest a new
      mechanism for hypertension.

PMID- 11581304
TI  - The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory
      cell recruitment and vascular cell activation.
AB  - Atherosclerosis causes most acute coronary syndromes and strokes. The
      pathogenesis of atherosclerosis includes recruitment of inflammatory cells to the
      vessel wall and activation of vascular cells. CD44 is an adhesion protein
      expressed on inflammatory and vascular cells. CD44 supports the adhesion of
      activated lymphocytes to endothelium and smooth muscle cells. Furthermore,
      ligation of CD44 induces activation of both inflammatory and vascular cells. To
      assess the potential contribution of CD44 to atherosclerosis, we bred CD44-null
      mice to atherosclerosis-prone apoE-deficient mice. We found a 50-70% reduction in
      aortic lesions in CD44-null mice compared with CD44 heterozygote and wild-type
      littermates. We demonstrate that CD44 promotes the recruitment of macrophages to
      atherosclerotic lesions. Furthermore, we show that CD44 is required for
      phenotypic dedifferentiation of medial smooth muscle cells to the "synthetic"
      state as measured by expression of VCAM-1. Finally, we demonstrate that
      hyaluronan, the principal ligand for CD44, is upregulated in atherosclerotic
      lesions of apoE-deficient mice and that the low-molecular-weight proinflammatory
      forms of hyaluronan stimulate VCAM-1 expression and proliferation of cultured
      primary aortic smooth muscle cells, whereas high-molecular-weight forms of
      hyaluronan inhibit smooth muscle cell proliferation. We conclude that CD44 plays
      a critical role in the progression of atherosclerosis through multiple
      mechanisms.

PMID- 11581305
TI  - Inhibition of IgE-mediated mast cell activation by the paired Ig-like receptor
      PIR-B.
AB  - The potential of the paired Ig-like receptors of activating (PIR-A) and
      inhibitory (PIR-B) types for modifying an IgE antibody-mediated allergic response
      was evaluated in mouse bone marrow-derived mast cells. Although mast cells
      produced both PIR-A and PIR-B, PIR-B was found to be preferentially expressed on
      the cell surface, where it was constitutively tyrosine phosphorylated and
      associated with intracellular SHP-1 protein tyrosine phosphatase. PIR-B
      coligation with the IgE receptor (FcepsilonRI) inhibited IgE-mediated mast cell
      activation and release of serotonin. Surprisingly, the inhibitory activity of PIR
      B was unimpaired in SHP-1-deficient mast cells. A third functional tyrosine-based
      inhibitory motif, one that fails to bind the SHP-1, SHP-2, and SHIP phosphatases,
      was identified in parallel studies of FcepsilonRI-bearing rat basophilic leukemia
      (RBL) cells transfected with constructs having mutations in the PIR-B cytoplasmic
      region. These results define the preferential expression of the PIR-B molecules
      on mast cells and an inhibitory potential that can be mediated via a SHP-1
      independent pathway.

PMID- 11581306
TI  - Mechanical stimulation activates Galphaq signaling pathways and 5
      hydroxytryptamine release from human carcinoid BON cells.
AB  - 5-Hydroxytryptamine (5-HT) released from enterochromaffin cells activates
      secretory and peristaltic reflexes necessary for lubrication and propulsion of
      intestinal luminal contents. The aim of this study was to identify
      mechanosensitive intracellular signaling pathways that regulate 5-HT release.
      Human carcinoid BON cells displayed 5-HT immunoreactivity associated with
      granules dispersed throughout the cells or at the borders. Mechanical stimulation
      by rotational shaking released 5-HT from BON cells or from guinea pig jejunum
      during neural blockade with tetrodotoxin. In streptolysin O-permeabilized cells,
      guanosine 5'-O- (2-thiodiphosphate) (GDP-beta-S) and a synthetic peptide derived
      from the COOH terminus of Galphaq abolished mechanically evoked 5-HT release,
      while the NH(2)-terminal peptide did not. An antisense phosphorothioated
      oligonucleotide targeted to a unique sequence of Galphaq abolished mechanically
      evoked 5-HT release and reduced Galphaq protein levels without affecting the
      expression of Galpha(11). Depletion and chelation of extracellular calcium did
      not alter mechanically evoked 5-HT release, whereas depletion of intracellular
      calcium stores by thapsigargin and chelation of intracellular calcium by 1,2-bis
      (o-Aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetra (acetoxymethyl) ester
      (BAPTA-AM) reduced 5-HT release. Mechanically evoked 5-HT release was inhibited
      by somatostatin-14 in a concentration-dependent manner. The results suggest that
      mechanical stimulation of enterochromaffin-derived BON cells directly or
      indirectly stimulates a G protein-coupled receptor that activates Galphaq,
      mobilizes intracellular calcium, and causes 5-HT release.

PMID- 11581307
TI  - Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human
      B cell tolerance.
AB  - The study of human B cell tolerance has been hampered by difficulties in
      identifying a sizable population of autoreactive B lymphocytes whose fate could
      be readily determined. Hypothesizing that B cells expressing intrinsically
      autoreactive antibodies encoded by the VH4-34 heavy chain gene (VH4-34 cells)
      represent such a population, we tracked VH4-34 cells in healthy individuals.
      Here, we show that naive VH4-34 cells are positively selected and mostly
      restricted to the follicular mantle zone. Subsequently, these cells are largely
      excluded from the germinal centers and underrepresented in the memory
      compartment. In healthy donors but not in patients with systemic lupus
      erythematosus (SLE), these cells are prevented from differentiating into antibody
      producing plasma cells. This blockade can be overcome ex vivo using cultures of
      naive and memory VH4-34 cells in the presence of CD70, IL-2, and IL-10. VH4-34
      cells may therefore represent an experimentally useful surrogate for autoantibody
      transgenes and should prove valuable in studying human B cell tolerance in a
      physiological, polyclonal environment. Our initial results suggest that both
      positive and negative selection processes participate in the maintenance of
      tolerance in autoreactive human B cells at multiple checkpoints throughout B cell
      differentiation and that at least some censoring mechanisms are faulty in SLE.

PMID- 11581308
TI  - Transplantable hematopoietic stem cells in human fetal liver have a CD34(+) side
      population (SP)phenotype.
AB  - Cells with a verapamil-sensitive ability to efflux Hoechst 33342 (termed side
      population [SP] cells) have been identified in adult marrow from several species
      including humans and in several tissues from adult mice. In mice, the SP
      phenotype appears to be a common feature of stem cells, but human SP cells have
      been less well characterized. We show here, for the first time to our knowledge,
      that SP cells are present in the second-trimester human fetal liver. They include
      all of the transplantable human hematopoietic stem cell activity detectable in
      NOD/SCID mice and also certain other, more differentiated hematopoietic cell
      types. Notably, the stem cell activity was confined to the CD34(+)CD38(-) SP(+)
      population, and isolation of these cells gave an approximately tenfold enrichment
      of transplantable stem cells. This subset was not, however, coenriched in
      hematopoietic progenitors detectable by either short- or long-term in vitro
      assays, indicating most of these to be distinct from transplantable stem cells.
      These findings suggest that the SP phenotype is an important and distinguishing
      property of human hematopoietic stem cells and that early in ontogeny they
      express CD34.

PMID- 11581309
TI  - Central melanocortin receptors regulate insulin action.
AB  - Energy balance and insulin action are tightly coregulated. Leptin regulates
      energy intake and expenditure partly by modulation of the melanocortin pathway in
      the hypothalamus. Here we demonstrate potent effects of the melanocortin pathway
      on insulin action and body distribution of adiposity. Conscious rats received
      week-long infusions of either a melanocortin receptor agonist, alpha-melanocyte
      stimulating hormone (alpha-MSH), or antagonist, SHU9119, in the third cerebral
      ventricle while food intake was maintained constant in each group. alpha-MSH
      decreased intra-abdominal fat and markedly enhanced the actions of insulin on
      both glucose uptake and production, while SHU9119 exerted opposite effects. Our
      findings elucidate a neuroendocrine network that is likely to play a central role
      in the coupling of energy intake and insulin action.

PMID- 11581310
TI  - Granulocyte macrophage colony-stimulating factor: a new putative therapeutic
      target in multiple sclerosis.
AB  - Experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis,
      can be induced by immunization with a number of myelin antigens. In particular,
      myelin oligodendrocyte glycoprotein, a central nervous system (CNS)-specific
      antigen expressed on the myelin surface, is able to induce a paralytic MS-like
      disease with extensive CNS inflammation and demyelination in several strains of
      animals. Although not well understood, the egress of immune cells into the CNS in
      EAE is governed by a complex interplay between pro and antiinflammatory cytokines
      and chemokines. The hematopoietic growth factor, granulocyte macrophage colony
      stimulating factor (GM-CSF), is considered to play a central role in maintaining
      chronic inflammation. The present study was designed to investigate the
      previously unexplored role of GM-CSF in autoimmune-mediated demyelination. GM
      CSF(-/)- mice are resistant to EAE, display decreased antigen-specific
      proliferation of splenocytes, and fail to sustain immune cell infiltrates in the
      CNS, thus revealing key activities for GM-CSF in the development of inflammatory
      demyelinating lesions and control of migration and/or proliferation of leukocytes
      within the CNS. These results hold implications for the pathogenesis of
      inflammatory and demyelinating diseases and may provide the basis for more
      effective therapies for inflammatory diseases, and more specifically for multiple
      sclerosis.

PMID- 11581311
TI  - A naturally processed mitochondrial self-peptide in complex with thymic MHC
      molecules functions as a selecting ligand for a viral-specific T cell receptor.
AB  - Peptide fragments of self-proteins bound to major histocompatibility complex
      molecules within the thymus are important for positively selecting T cell
      receptor (TCR)-bearing CD4(+)CD8(+) double positive (DP) thymocytes for further
      maturation. The relationship between naturally processed thymic self-peptides and
      TCR-specific cognate peptides is unknown. Here we employ HPLC purification of
      peptides released from H-2K(b) molecules of the C57BL/6 thymus in conjunction
      with mass spectrometry (MS) and functional profiling to identify a naturally
      processed K(b)-bound peptide positively selecting the N15 TCR specific for the
      vesicular stomatitis virus octapeptide (VSV8) bound to K(b). The selecting
      peptide was identified in 1 of 80 HPLC fractions and shown by tandem MS (MS/MS)
      sequencing to correspond to residues 68-75 of the MLRQ subunit of the widely
      expressed mitochondrial NADH ubiquinone oxidoreductase (NUbO(68-75)). Of note,
      the peptide differs at six of its eight residues from the cognate peptide VSV8
      and functions as a weak agonist for mature CD8 single positive (SP) N15 T cells,
      with activity 10,000-fold less than VSV8. In N15 transgenic (tg) recombinase
      activating gene 2(-/)- transporter associated with antigen processing 1(-/)-
      fetal thymic organ culture, NUbO(68-75) induces phenotypic and functional
      differentiation of N15 TCR bearing CD8 SP thymocytes. Failure of NUbO(68-75) to
      support differentiation of a second K(b)-restricted TCR indicates that its
      inductive effects are not general.

PMID- 11581312
TI  - Induction of cytotoxic T lymphocyte antigen 4 (CTLA-4) restricts clonal expansion
      of helper T cells.
AB  - Cytotoxic T lymphocyte antigen (CTLA)-4 plays an essential role in immunologic
      homeostasis. How this negative regulator of T cell activation executes its
      functions has remained controversial. We now provide evidence that CTLA-4
      mediates a cell-intrinsic counterbalance to restrict the clonal expansion of
      proliferating CD4(+) T cells. The regulation of CTLA-4 expression and function
      ensures that, after approximately 3 cell divisions of expansion, most progeny
      will succumb to either proliferative arrest or death over the ensuing three cell
      divisions. The quantitative precision of the counterbalance hinges on the graded,
      time-independent induction of CTLA-4 expression during the first three cell
      divisions. In contrast to the limits imposed on unpolarized cells, T helper type
      1 (Th1) and Th2 effector progeny may be rescued from proliferative arrest by
      interleukin (IL)-12 and IL-4 signaling, respectively, allowing appropriately
      stimulated progeny to proceed to the stage of tissue homing. These results
      suggest that the cell-autonomous regulation of CTLA-4 induction may be a central
      checkpoint of clonal expansion of CD4(+) T cells, allowing temporally and
      spatially restricted growth of progeny to be dictated by the nature of the threat
      posed to the host.

PMID- 11581313
TI  - Analysis of thymocyte development reveals that the GTPase RhoA is a positive
      regulator of T cell receptor responses in vivo.
AB  - Loss of function of the guanine nucleotide binding protein RhoA blocks pre-T cell
      differentiation and survival indicating that this GTPase is a critical signaling
      molecule during early thymocyte development. Previous work has shown that the Rho
      family GTPase Rac-1 can initiate changes in actin dynamics necessary and
      sufficient for pre-T cell development. The present data now show that Rac-1
      actions in pre-T cells require Rho function but that RhoA cannot substitute for
      Rac-1 and induce the actin cytoskeletal changes necessary for pre-T cell
      development. Activation of Rho is thus not sufficient to induce pre-T cell
      differentiation or survival in the absence of the pre-T cell receptor (TCR). The
      failure of RhoA activation to impact on pre-TCR-mediated signaling was in marked
      contrast to its actions on T cell responses mediated by the mature TCR alpha/beta
      complex. Cells expressing active RhoA were thus hyperresponsive in the context of
      TCR-induced proliferation in vitro and in vivo showed augmented positive
      selection of thymocytes expressing defined TCR complexes. This reveals that RhoA
      function is not only important for pre-T cells but also plays a role in
      determining the fate of mature T cells.

PMID- 11581314
TI  - Deficiency of small GTPase Rac2 affects T cell activation.
AB  - Rac2 is a hematopoietic-specific GTPase acting as a molecular switch to mediate
      both transcriptional activation and cell morphological changes. We have examined
      the effect of Rac2 deficiency during T cell activation. In Rac2(-/-) T cells,
      proliferation was reduced upon stimulation with either plate-bound anti-CD3 or T
      cell receptor-specific antigen. This defect is accompanied with decreased
      activation of mitogen activated protein kinase extracellular signal-regulated
      kinase (ERK)1/2 and p38, and reduced Ca(2)+ mobilization. TCR stimulation-induced
      actin polymerization is also reduced. In addition, anti-CD3 cross-linking-induced
      T cell capping is reduced compared with wild-type T cells. These results indicate
      that Rac2 is important in mediating both transcriptional and cytoskeletal changes
      during T cell activation. The phenotypic similarity of Rac2(-/-) to Vav(-/-)
      cells implicates Rac2 as a downstream mediator of Vav signaling.

PMID- 11581315
TI  - Survival and clonal expansion of mutating "forbidden" (immunoglobulin receptor
      deficient) epstein-barr virus-infected b cells in angioimmunoblastic t cell
      lymphoma.
AB  - Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a peculiar T
      cell lymphoma, as expanding B cell clones are often present besides the malignant
      T cell clones. In addition, large numbers of Epstein-Barr virus (EBV)-infected B
      cells are frequently observed. To analyze the differentiation status and clonal
      composition of EBV-harboring B cells in AILD, single EBV-infected cells were
      micromanipulated from lymph nodes of six patients with frequent EBV(+) cells and
      their rearranged immunoglobulin (Ig) genes analyzed. Most EBV-infected B cells
      carried mutated Ig genes, indicating that in AILD, EBV preferentially resides in
      memory and/or germinal center B cells. EBV(+) B cell clones observed in all six
      cases ranged from small polyclonal to large monoclonal expansions and often
      showed ongoing somatic hypermutation while EBV(-) B cells showed little tendency
      for clonal expansion. Surprisingly, many members of expanding B cell clones had
      acquired destructive mutations in originally functional V gene rearrangements and
      showed an unfavorable high load of replacement mutations in the framework
      regions, indicating that they accumulated mutations over repeated rounds of
      mutation and division while not being selected through their antigen receptor.
      This sustained selection-free accumulation of somatic mutations is unique to
      AILD. Moreover, the survival and clonal expansion of "forbidden" (i.e., Ig
      deficient) B cells has not been observed before in vivo and thus represents a
      novel type of viral latency in the B cell compartment. It is likely the interplay
      between the microenvironment in AILD lymph nodes and the viral transformation
      that leads to the survival and clonal expansion of Ig-less B cells.

PMID- 11581316
TI  - Self-renewal of multipotent long-term repopulating hematopoietic stem cells is
      negatively regulated by Fas and tumor necrosis factor receptor activation.
AB  - Multipotent self-renewing hematopoietic stem cells (HSCs) are responsible for
      reconstitution of all blood cell lineages. Whereas growth stimulatory cytokines
      have been demonstrated to promote HSC self-renewal, the potential role of
      negative regulators remains elusive. Receptors for tumor necrosis factor (TNF)
      and Fas ligand have been implicated as regulators of steady-state hematopoiesis,
      and if overexpressed mediate bone marrow failure. However, it has been proposed
      that hematopoietic progenitors rather than stem cells might be targeted by Fas
      activation. Here, murine Lin(-)Sca1(+)c-kit(+) stem cells revealed little or no
      constitutive expression of Fas and failed to respond to an agonistic anti-Fas
      antibody. However, if induced to undergo self-renewal in the presence of TNF
      alpha, the entire short and long-term repopulating HSC pool acquired Fas
      expression at high levels and concomitant activation of Fas suppressed in vitro
      growth of Lin(-)Sca1(+)c-kit(+) cells cultured at the single cell level.
      Moreover, Lin(-)Sca1(+)c-kit(+) stem cells undergoing self-renewal divisions in
      vitro were severely and irreversibly compromised in their short- and long-term
      multilineage reconstituting ability if activated by TNF-alpha or through Fas,
      providing the first evidence for negative regulators of HSC self-renewal.

PMID- 11581317
TI  - Migratory properties of naive, effector, and memory CD8(+) T cells.
AB  - It has been proposed that two different antigen-experienced T cell subsets may be
      distinguishable by their preferential ability to home to lymphoid organs (central
      memory cells) or nonlymphoid tissues (effector memory/effector cells). We have
      shown recently that murine antigen-primed CD8(+) T cells cultured in interleukin
      (IL)-15 (CD8(IL-15)) resemble central memory cells in phenotype and function. In
      contrast, primed CD8(+) T cells cultured in IL-2 (CD8(IL-2)) become cytotoxic
      effector cells. Here, the migratory behavior of these two subsets was
      investigated. Naive, CD8(IL-15) cells and, to a lesser degree, CD8(IL-2) cells
      localized to T cell areas in the spleen, but only naive and CD8(IL-15) cells
      homed to lymph nodes (LNs) and Peyer's patches. Intravital microscopy of
      peripheral LNs revealed that CD8(IL-15) cells, but not CD8(IL-2) cells, rolled
      and arrested in high endothelial venules (HEVs). Migration of CD8(IL-15) cells to
      LNs depended on L-selectin and required chemokines that bind CC chemokine
      receptor (CCR)7. Both antigen-experienced populations, but not naive T cells,
      responded to inflammatory chemokines and accumulated at sites of inflammation.
      However, CD8(IL-2) cells were 12 times more efficient in migrating to inflamed
      peritoneum than CD8(IL-15) cells. Furthermore, CD8(IL-15) cells proliferated
      rapidly upon reencounter with antigen at sites of inflammation. Thus, central
      memory-like CD8(IL-15) cells home avidly to lymphoid organs and moderately to
      sites of inflammation, where they mediate rapid recall responses, whereas CD8(IL
      2) effector T cells accumulate in inflamed tissues, but are excluded from most
      lymphoid organs.

PMID- 11581318
TI  - The multiple immune-evasion genes of murine cytomegalovirus are not redundant: m4
      and m152 inhibit antigen presentation in a complementary and cooperative fashion.
AB  - Both human cytomegaloviruses (HCMVs) and murine cytomegaloviruses (MCMVs) encode
      multiple genes that interfere with antigen presentation by major
      histocompatibility complex (MHC) class I, and thus protect infected targets from
      lysis by virus-specific cytotoxic T lymphocytes (CTLs). HCMV has been shown to
      encode four such genes and MCMV to encode two. MCMV m152 blocks the export of
      class I from a pre-Golgi compartment, and MCMV m6 directs class I to the lysosome
      for degradation. A third MCMV gene, m4, encodes a glycoprotein which is expressed
      at the cell surface in association with class I. Here we here show that m4 is a
      CTL-evasion gene which, unlike previously described immune-evasion genes,
      inhibited CTLs without blocking class I surface expression. m152 was necessary to
      block antigen presentation to both K(b)- and D(b)-restricted CTL clones, while m4
      was necessary to block presentation only to K(b)-restricted clones. m152 caused
      complete retention of D(b), but only partial retention of K(b), in a pre-Golgi
      compartment. Thus, while m152 effectively inhibited D(b)-restricted CTLs, m4 was
      required to completely inhibit K(b)-restricted CTLs. We propose that
      cytomegaloviruses encode multiple immune-evasion genes in order to cope with the
      diversity of class I molecules in outbred host populations.

PMID- 11581319
TI  - The upstream enhancer is necessary and sufficient for the expression of the pre-T
      cell receptor alpha gene in immature T lymphocytes.
AB  - The expression of the pre-T cell receptor alpha (pTa) gene occurs exclusively in
      immature T lymphocytes and is regulated by poorly defined mechanisms. We have
      analyzed the role of the upstream enhancer in pTa expression using conventional
      and bacterial artificial chromosome (BAC) reporter transgenes. The deletion of
      the enhancer completely abolished the expression of pTa BAC reporter in
      transgenic mice. Conversely, the combination of pTa enhancer and promoter
      targeted transgenes specifically to immature thymocytes, recapitulating the
      expression pattern of pTa. The core enhancer is conserved between mice and humans
      and contains a critical binding site for the transcription factor c-Myb. We also
      show that pTa promoter contains a conserved tandem E box site activated by E
      protein, HEB. These data establish the enhancer as a critical element regulating
      pTa gene expression and identify additional targets for c-Myb and E proteins in T
      cell development.

PMID- 11581321
TI  - Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus.
AB  - We have recently reported that Notch 1, a member of the Notch multigene family,
      is essential for the development of murine T cells. Using a mouse model in which
      Notch 1 is inactivated in bone marrow (BM) precursors we have shown that B cells
      instead of T cells are found in the thymus of BM chimeras. However, it is not
      clear whether these B cells develop by default from a common lymphoid precursor
      due to the absence of Notch 1 signaling, or whether they arise as a result of
      perturbed migration of BM-derived B cells and/or altered homeostasis of normal
      resident thymic B cells. In this report we show that Notch 1-deficient thymic B
      cells resemble BM B cells in phenotype and turnover kinetics and are located
      predominantly in the medulla and corticomedullary junction. Peripheral blood
      lymphocyte analysis shows no evidence of recirculating Notch1(-/)- BM B cells.
      Furthermore, lack of T cell development is not due to a failure of Notch1(-/)-
      precursors to home to the thymus, as even after intrathymic reconstitution with
      BM cells, B cells instead of T cells develop from Notch 1-deficient precursors.
      Taken together, these results provide evidence for de novo ectopic B cell
      development in the thymus, and support the hypothesis that in the absence of
      Notch 1 common lymphoid precursors adopt the default cell fate and develop into B
      cells instead.

PMID- 11581320
TI  - Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid
      differentiation.
AB  - Notch signaling is known to differentially affect the development of lymphoid B
      and T cell lineages, but it remains unclear whether such effects are specifically
      dependent on distinct Notch ligands. Using a cell coculture assay we observed
      that the Notch ligand Delta-1 completely inhibits the differentiation of human
      hematopoietic progenitors into the B cell lineage while promoting the emergence
      of cells with a phenotype of T cell/natural killer (NK) precursors. In contrast,
      Jagged-1 did not disturb either B or T cell/NK development. Furthermore, cells
      cultured in the presence of either Delta-1 or Jagged-1 can acquire a phenotype of
      NK cells, and Delta-1, but not Jagged-1, permits the emergence of a de novo cell
      population coexpressing CD4 and CD8. Our results thus indicate that distinct
      Notch ligands can mediate differential effects of Notch signaling and provide a
      useful system to further address cell-fate decision processes in lymphopoiesis.

PMID- 11581322
TI  - Interleukin 15 skews monocyte differentiation into dendritic cells with features
      of Langerhans cells.
AB  - Langerhans cells (LCs) represent a subset of immature dendritic cells (DCs)
      specifically localized in the epidermis and other mucosal epithelia. As
      surrounding keratinocytes can produce interleukin (IL)-15, a cytokine that
      utilizes IL-2Rgamma chain, we analyzed whether IL-15 could skew monocyte
      differentiation into LCs. Monocytes cultured for 6 d with granulocyte/macrophage
      colony-stimulating factor (GM-CSF) and IL-15 differentiate into CD1a(+)HLA
      DR(+)CD14(-)DCs (IL15-DCs). Agents such as lipopolysaccharide (LPS), tumor
      necrosis factor (TNF)alpha, and CD40L induce maturation of IL15-DCs to CD83(+),
      DC-LAMP(+) cells. IL15-DCs are potent antigen-presenting cells able to induce the
      primary (mixed lymphocyte reaction [MLR]) and secondary (recall responses to flu
      matrix peptide) immune responses. As opposed to cultures made with GM-CSF/IL-4
      (IL4-DCs), a proportion of IL15-DCs expresses LC markers: E-Cadherin, Langerin,
      and CC chemokine receptor (CCR)6. Accordingly, IL15-DCs, but not IL4-DCs, migrate
      in response to macrophage inflammatory protein (MIP)-3alpha/CCL20. However, IL15
      DCs cannot be qualified as "genuine" Langerhans cells because, despite the
      presence of the 43-kD Langerin, they do not express bona fide Birbeck granules.
      Thus, our results demonstrate a novel pathway in monocyte differentiation into
      dendritic cells.

PMID- 11581323
TI  - Coming to grips with Notch.

PMID- 11581324
TI  - Limits to human performance: elevated risks on high mountains.
AB  - In 1950, Maurice Herzog and Louis Lachenal became the first climbers to reach the
      summit of an 8000m peak (Annapurna, 8091m). In the half century since that
      pioneering climb, mountaineers have increasingly sought to climb the fourteen '8K
      peaks' of the Himalayas and Karakoram, with remarkable success; they have made
      5085 ascents of those peaks up to the year 2000. While seeking adventure on those
      great peaks, mountaineers are inevitably exposed to hypoxia, cold and dehydration
      as well as to the physical hazards of climbing. Those few mountaineers who
      successfully summit an 8K peak are likely to be at or near their physiological
      limits and probably confront an elevated probability of dying during their
      descent. We will briefly review some of the physiological challenges climbers
      face at extreme elevation and then compare success rates and death rates on
      mountains of different heights (Rainer, Foraker, Denali, K2, Everest). Success
      rates decline with summit height, but overall death rates and death rates during
      descent from the summit increase with summit height. Although these patterns are
      based on non-experimental and uncontrolled data, our findings are consistent with
      the hypothesis that increasing altitude is associated with decreased success and
      with increased risk of death.

PMID- 11581325
TI  - Limits of human lung function at high altitude.
AB  - This paper will review the function of the lung at high altitude in humans. As
      the first interface between the environment and the body, the lung serves a vital
      role in the transfer of oxygen from the air to the blood. I will describe the
      limits of response and adaptation of the lung to this hypoxic stress, both at
      rest and during exercise when oxygen and carbon dioxide flux from the tissues is
      greater. First, ventilation will be described in terms of the hypoxic stimulus
      that causes an increase in breathing (ventilatory drives) and the metabolic cost
      from the respiratory muscles incurred by this increase. Individuals at high
      altitude also have a substantial sense of dyspnea which, in and of itself, may
      limit exercise tolerance. The final function of the lung is to exchange oxygen
      and carbon dioxide, which it does at the alveolar-capillary interface. Here,
      important limitations are encountered because the driving pressure for oxygen
      from the air to the blood is lower and the more rapid transit time of blood
      across the pulmonary capillary allows less time for equilibration of oxygen with
      the blood. Both these phenomena lead to a limitation of diffusion of oxygen
      across the alveolar-capillary membrane and, thus, more accentuated hypoxemia. In
      spite of these restrictions, humans still do remarkably well in times of great
      stress from the hypoxic environment.

PMID- 11581326
TI  - The high-altitude brain.
AB  - The highest place on our planet, Mount Everest (8850 m), appears to be close to
      the limit of how high an acclimatized human can go, albeit slowly. In this paper,
      I will explore the possibility that what limits human performance at such extreme
      degrees of hypoxia is the availability of oxygen to the brain. Also, one of the
      known costs of such extreme exposure is residual mild impairment of performance
      on neuropsychometric tests after return to sea level, implying injury to brain
      cells. That such injury could occur in the absence of any overt impairment of
      function, much less without loss of consciousness, is unexpected. I will
      speculate about physiological mechanisms that might cause or contribute to both
      decrements in real-time performance while at altitude and residual deficits for a
      time after return to low elevations; the effects of hypoxia on brain cells are an
      even greater puzzle at the present time.

PMID- 11581327
TI  - Muscle tissue adaptations to hypoxia.
AB  - This review reports on the effects of hypoxia on human skeletal muscle tissue. It
      was hypothesized in early reports that chronic hypoxia, as the main physiological
      stress during exposure to altitude, per se might positively affect muscle
      oxidative capacity and capillarity. However, it is now established that sustained
      exposure to severe hypoxia has detrimental effects on muscle structure. Short
      term effects on skeletal muscle structure can readily be observed after 2 months
      of acute exposure of lowlanders to severe hypoxia, e.g. during typical
      mountaineering expeditions to the Himalayas. The full range of phenotypic
      malleability of muscle tissue is demonstrated in people living permanently at
      high altitude (e.g. at La Paz, 3600-4000 m). In addition, there is some evidence
      for genetic adaptations to hypoxia in high-altitude populations such as Tibetans
      and Quechuas, who have been exposed to altitudes in excess of 3500 m for
      thousands of generations. The hallmark of muscle adaptation to hypoxia in all
      these cases is a decrease in muscle oxidative capacity concomitant with a
      decrease in aerobic work capacity. It is thought that local tissue hypoxia is an
      important adaptive stress for muscle tissue in exercise training, so these
      results seem contra-intuitive. Studies have therefore been conducted in which
      subjects were exposed to hypoxia only during exercise sessions. In this
      situation, the potentially negative effects of permanent hypoxic exposure and
      other confounding variables related to exposure to high altitude could be
      avoided. Training in hypoxia results, at the molecular level, in an upregulation
      of the regulatory subunit of hypoxia-inducible factor-1 (HIF-1). Possibly as a
      consequence of this upregulation of HIF-1, the levels mRNAs for myoglobin, for
      vascular endothelial growth factor and for glycolytic enzymes, such as
      phosphofructokinase, together with mitochondrial and capillary densities,
      increased in a hypoxia-dependent manner. Functional analyses revealed positive
      effects on V(O(2)max) (when measured at altitude) on maximal power output and on
      lean body mass. In addition to the positive effects of hypoxia training on
      athletic performance, there is some recent indication that hypoxia training has a
      positive effect on the risk factors for cardiovascular disease.

PMID- 11581328
TI  - The home team advantage: reproduction in women indigenous to high altitude.
AB  - Although there is substantial evidence that environmental conditions disrupt
      reproductive function among newcomers to hypoxic settings, it is not certain that
      low oxygen pressure reduces fertility among those indigenous to high altitude.
      Even when fertility does appear to be relatively lower, numerous behavioral and
      sociocultural factors may be responsible. These are best examined within
      demographic frameworks that delineate a finite list of the proximate determinants
      of fertility. The findings presented here are based on several studies of
      indigenous Andean populations (Peruvian Quechua at 4000 m, Bolivian Quechua at
      3100 m, Bolivian Aymara at 4000 m). Data on ovarian function suggest that neither
      progesterone levels nor menstrual cycle length or regularity are significantly
      different from those of women at lower altitudes. Data on two behavioral factors
      that determine fertility levels, coital frequency and infant feeding practices,
      suggest that the former is not likely to be of significance in co-habitating
      couples, but that variation in breastfeeding patterns has probably made a
      substantial contribution to differences in fertility among at least some
      populations at high altitude.

PMID- 11581329
TI  - Genetic approaches to understanding human adaptation to altitude in the Andes.
AB  - Despite the initial discomfort often experienced by visitors to high altitude,
      humans have occupied the Andean altiplano for more than 10000 years, and millions
      of people, indigenous and otherwise, currently live on these plains, high in the
      mountains of South America, at altitudes exceeding 3000 m. While, to some extent,
      acclimatization can accommodate the one-third decrease in oxygen availability,
      having been born and raised at altitude appears to confer a substantial advantage
      in high-altitude performance compared with having been born and raised at sea
      level. A number of characteristics have been postulated to contribute to a high
      altitude Andean phenotype; however, the relative contributions of developmental
      adaptation (within the individual) and genetic adaptation (within the population
      of which the individual is part) to the acquisition of this phenotype have yet to
      be resolved. A complex trait is influenced by multiple genetic and environmental
      factors and, in humans, it is inherently very difficult to determine what
      proportion of the trait is dictated by an individual's genetic heritage and what
      proportion develops in response to the environment in which the person is born
      and raised. Looking for changes in putative adaptations in vertically migrant
      populations, determining the heritability of putative adaptive traits and genetic
      association analyses have all been used to evaluate the relative contributions of
      nurture and nature to the Andean phenotype. As the evidence for a genetic
      contribution to high-altitude adaptation in humans has been the subject of
      several recent reviews, this article instead focuses on the methodology that has
      been employed to isolate the effects of 'nature' from those of 'nurture' on the
      acquisition of the high-altitude phenotype in Andean natives (Quechua and
      Aymara). The principles and assumptions underlying the various approaches, as
      well as some of the inherent strengths and weaknesses of each, are briefly
      discussed.

PMID- 11581330
TI  - Frontiers of hypoxia research: acute mountain sickness.
AB  - Traditionally, scientists and clinicians have explored peripheral physiological
      responses to acute hypoxia to explain the pathophysiological processes that lead
      to acute mountain sickness (AMS) and high-altitude cerebral edema (HACE). After
      more than 100 years of investigation, little is yet known about the fundamental
      causes of the headache and nausea that are the main symptoms of AMS. Thus, we
      review the evidence supporting a change in focus to the role of the central
      nervous system in AMS. Our justification is (i) that the symptoms of AMS and HACE
      are largely neurological, (ii) that HACE is considered to be the end-stage of
      severe AMS and was recently identified as a vasogenic edema, opening the door for
      a role for blood-brain barrier permeability in AMS, (iii) that new, non-invasive
      techniques make measurement of brain water levels and cerebral blood volume
      possible and (iv) that the available experimental evidence and theoretical
      arguments support a significant role for brain swelling in the pathophysiology of
      AMS. We believe that an examination of the responses of the central nervous
      system to acute hypoxia will reveal important new pathophysiological processes
      that may help explain AMS and HACE.

PMID- 11581331
TI  - Mechanisms of cell survival in hypoxia and hypothermia.
AB  - Most animals experience some degree of hypoxia and hypothermia during the course
      of their natural life history either as a consequence of ambient 'exposure' per
      se or through metabolic, respiratory and/or circulatory insufficiency. A
      prevailing experimental approach has been to probe tissues from natural models of
      hypoxia-tolerant and cold-tolerant vertebrates to look for common mechanisms of
      defence against O(2) lack and hypothermia. The ability to sustain vital cellular
      functions in severe cases of either condition varies widely amongst the
      vertebrates. Like humans, the vast majority of mammals are unable to survive
      prolonged periods of hypothermia or O(2) deprivation owing to irreversible
      membrane damage and loss of cellular ion homeostasis in vital organs such as the
      brain and heart. However, numerous hibernating endotherms, neonatal and diving
      mammals as well as many ectotherms can tolerate prolonged periods that would, in
      clinical terms, be called asphyxia or deep hypothermia. The key to their survival
      under such conditions lies in an inherent ability to downregulate their cellular
      metabolic rate to new hypometabolic steady states in a way that balances the ATP
      demand and ATP supply pathways.

PMID- 11581332
TI  - Limits to sustainable human metabolic rate.
AB  - There is a limit to the performance of an organism set by energy intake and
      energy mobilization. Here, the focus is on humans with unlimited access to food
      and for whom physical activity can be limited by energy mobilization. The
      physical activity level (PAL) in the general population, calculated as doubly
      labelled-water-assessed average daily metabolic rate as a multiple of basal
      metabolic rate, has an upper limit of 2.2-2.5. The upper limit of sustainable
      metabolic rate is approximately twice as high in endurance athletes, mainly
      because of long-term exercise training with simultaneous consumption of
      carbohydrate-rich food during exercise. Endurance athletes have an increased fat
      free mass and can maintain energy balance at a PAL value of 4.0-5.0. High
      altitude limits exercise performance as a result of combined effects on nutrient
      supply and the capacity to process nutrients. Thus, trained subjects climbing
      Mount Everest reached PAL values of 2.0-2.7, well below the observed upper limit
      at sea level.

PMID- 11581333
TI  - Limits to sustainable muscle performance: interaction between glycolysis and
      oxidative phosphorylation.
AB  - This paper proposes a mechanism responsible for setting the sustainable level of
      muscle performance. Our contentions are that the sustainable work rate is
      determined (i) at the muscle level, (ii) by the ability to maintain ATP supply
      and (iii) by the products of glycolysis that may inhibit the signal for oxidative
      phosphorylation. We argue below that no single factor 'limits' sustainable
      performance, but rather that the flux through and the interaction between
      glycolysis and oxidative phosphorylation set the level of sustainable ATP supply.
      This argument is based on magnetic resonance spectroscopy measurements of the
      sources and sinks for energy in vivo in human muscle and rattlesnake tailshaker
      muscle during sustained contractions. These measurements show that glycolysis
      provides between 20% (human muscle) and 40% (tailshaker muscle) of the ATP supply
      during sustained contractions in these muscles. We cite evidence showing that
      this high glycolytic flux does not reflect an O(2) limitation or mitochondria
      operating at their capacity. Instead, this flux reflects a pathway independent of
      oxidative phosphorylation for ATP supply during aerobic exercise. The consequence
      of this high glycolytic flux is accumulation of H(+), which we argue inhibits the
      rise in the signal activating oxidative phosphorylation, thereby restricting
      oxidative ATP supply to below the oxidative capacity. Thus, both glycolysis and
      oxidative phosphorylation play important roles in setting the highest steady
      state ATP synthesis flux and thereby determine the sustainable level of work by
      exercising muscle.

PMID- 11581334
TI  - Human aerobic performance: too much ado about limits to V(O(2)).
AB  - Human endurance performance is often evaluated on the basis of the maximal rate
      of oxygen uptake during exercise (V(O(2)max)). Methods for overcoming limits to
      V(O(2)max) are touted as means for increasing athletic endurance performance.
      Here, we argue that the respiratory system is well designed for delivering O(2)
      to meet O(2) demands and that no single factor is rate-determining for O(2)
      uptake. We show that V(O(2)max) can vary 5000-fold among mammals, while any
      limitation to O(2) delivery by a single component of the respiratory system
      affects V(O(2)max) by 10% or less. Attempts to increase O(2) delivery by
      enhancing one step in the respiratory system are shown to have little effect.
      Blood doping, hyperoxia and O(2) supplementation of high-altitude natives all
      raise O(2) availability substantially to the working muscles, but these
      treatments increase V(O(2)max) only minimally. Finally, we argue that O(2) uptake
      is only one of a number of properties important to human aerobic performance.

PMID- 11581335
TI  - Functional and structural adaptations of skeletal muscle to microgravity.
AB  - Our purpose is to summarize the major effects of space travel on skeletal muscle
      with particular emphasis on factors that alter function. The primary deleterious
      changes are muscle atrophy and the associated decline in peak force and power.
      Studies on both rats and humans demonstrate a rapid loss of cell mass with
      microgravity. In rats, a reduction in muscle mass of up to 37% was observed
      within 1 week. For both species, the antigravity soleus muscle showed greater
      atrophy than the fast-twitch gastrocnemius. However, in the rat, the slow type I
      fibers atrophied more than the fast type II fibers, while in humans, the fast
      type II fibers were at least as susceptible to space-induced atrophy as the slow
      fiber type. Space flight also resulted in a significant decline in peak force.
      For example, the maximal voluntary contraction of the human plantar flexor
      muscles declined by 20-48% following 6 months in space, while a 21% decline in
      the peak force of the soleus type I fibers was observed after a 17-day shuttle
      flight. The reduced force can be attributed both to muscle atrophy and to a
      selective loss of contractile protein. The former was the primary cause because,
      when force was expressed per cross-sectional area (kNm(-2)), the human fast type
      II and slow type I fibers of the soleus showed no change and a 4% decrease in
      force, respectively. Microgravity has been shown to increase the shortening
      velocity of the plantar flexors. This increase can be attributed both to an
      elevated maximal shortening velocity (V(0)) of the individual slow and fast
      fibers and to an increased expression of fibers containing fast myosin. Although
      the cause of the former is unknown, it might result from the selective loss of
      the thin filament actin and an associated decline in the internal drag during
      cross-bridge cycling. Despite the increase in fiber V(0), peak power of the slow
      type I fiber was reduced following space flight. The decreased power was a direct
      result of the reduced force caused by the fiber atrophy. In addition to fiber
      atrophy and the loss of force and power, weightlessness reduces the ability of
      the slow soleus to oxidize fats and increases the utilization of muscle glycogen,
      at least in rats. This substrate change leads to an increased rate of fatigue.
      Finally, with return to the 1g environment of earth, rat studies have shown an
      increased occurrence of eccentric contraction-induced fiber damage. The damage
      occurs with re-loading and not in-flight, but the etiology has not been
      established.

PMID- 11581336
TI  - Fluid volume control during short-term space flight and implications for human
      performance.
AB  - Space flight exerts substantial effects on fluid volume control in humans.
      Cardiac distension occurs during the first 1-2 days of space flight relative to
      supine and especially upright 1g conditions. Plasma volume contraction occurs
      quickly in microgravity, probably as a result of transcapillary fluid filtration
      into upper-body interstitial spaces. No natriuresis or diuresis has been observed
      in microgravity, such that diuresis cannot explain microgravity-induced
      hypovolemia. Reduction of fluid intake occurs irrespective of space motion
      sickness and leads to hypovolemia. The fourfold elevation of urinary antidiuretic
      hormone (ADH) levels on flight day 1 probably results from acceleration exposures
      and other stresses of launch. Nevertheless, it is fascinating that elevated ADH
      levels and reduced fluid intake occur simultaneously early in flight.
      Extracellular fluid volume decreases by 10-15% in microgravity, and intracellular
      fluid volume appears to increase. Total red blood cell mass decreases by
      approximately 10% within 1 week in space. Inflight Na(+) and volume excretory
      responses to saline infusion are approximately half those seen in pre-flight
      supine conditions. Fluid volume acclimation to microgravity sets the central
      circulation to homeostatic conditions similar to those found in an upright
      sitting posture on Earth. Fluid loss in space contributes to reduced exercise
      performance upon return to 1g, although not necessarily in flight. In-flight
      exercise training may help prevent microgravity-induced losses of fluid and,
      therefore, preserve the capacity for upright exercise post-flight. Protection of
      orthostatic tolerance during space flight probably requires stimulation of
      orthostatic blood pressure control systems in addition to fluid maintenance or
      replacement.

PMID- 11581337
TI  - Sensorimotor adaptations to microgravity in humans.
AB  - Motor function is altered by microgravity, but little detail is available as to
      what these changes are and how changes in the individual components of the
      sensorimotor system affect the control of movement. Further, there is little
      information on whether the changes in motor performance reflect immediate or
      chronic adaptations to changing gravitational environments. To determine the
      effects of microgravity on the neural control properties of selected motor pools,
      four male astronauts from the NASA STS-78 mission performed motor tasks requiring
      the maintenance of either ankle dorsiflexor or plantarflexor torque. Torques of
      10 or 50% of a maximal voluntary contraction (MVC) were requested of the subjects
      during 10 degrees peak-to-peak sinusoidal movements at 0.5 Hz. When 10% MVC of
      the plantarflexors was requested, the actual torques generated in-flight were
      similar to pre-flight values. Post-flight torques were higher than pre- and in
      flight torques. The actual torques when 50% MVC was requested were higher in- and
      post-flight than pre-flight. Soleus (Sol) electromyographic (EMG) amplitudes
      during plantarflexion were higher in-flight than pre- or post-flight for both the
      10 and 50% MVC tasks. No differences in medial gastrocnemius (MG) EMG amplitudes
      were observed for either the 10 or 50% MVC tasks. The EMG amplitudes of the
      tibialis anterior (TA), an antagonist to plantarflexion, were higher in- and post
      flight than pre-flight for the 50% MVC task. During the dorsiflexion tasks, the
      torques generated in both the 10 and 50% MVC tasks did not differ pre-, in- and
      post-flight. TA EMG amplitudes were significantly higher in- than pre-flight for
      both the 10 or 50% MVC tasks, and remained elevated post-flight for the 50% MVC
      test. Both the Sol and MG EMG amplitudes were significantly higher in-flight than
      either pre- or post-flight for both the 10 and 50% MVC tests. These data suggest
      that the most consistent response to space flight was an elevation in the level
      of contractions of agonists and antagonists when attempting to maintain constant
      torques at a given level of MVC. Also, the chronic levels of EMG activity in
      selected ankle flexor and extensor muscles during space flight and during routine
      activities on Earth were recorded. Compared with pre- and post-flight values,
      there was a marked increase in the total EMG activity of the TA and the Sol and
      no change in the MG EMG activity in-flight. These data indicate that space
      flight, as occurs on shuttle missions, is a model of elevated activation of both
      flexor and extensor muscles, probably reflecting the effects of programmed work
      schedules in flight rather than a direct effect of microgravity.

PMID- 11581338
TI  - Evidence that a central governor regulates exercise performance during acute
      hypoxia and hyperoxia.
AB  - An enduring hypothesis in exercise physiology holds that a limiting
      cardiorespiratory function determines maximal exercise performance as a result of
      specific metabolic changes in the exercising skeletal muscle, so-called
      peripheral fatigue. The origins of this classical hypothesis can be traced to
      work undertaken by Nobel Laureate A. V. Hill and his colleagues in London between
      1923 and 1925. According to their classical model, peripheral fatigue occurs only
      after the onset of heart fatigue or failure. Thus, correctly interpreted, the
      Hill hypothesis predicts that it is the heart, not the skeletal muscle, that is
      at risk of anaerobiosis or ischaemia during maximal exercise. To prevent
      myocardial damage during maximal exercise, Hill proposed the existence of a
      'governor' in either the heart or brain to limit heart work when myocardial
      ischaemia developed. Cardiorespiratory function during maximal exercise at
      different altitudes or at different oxygen fractions of inspired air provides a
      definitive test for the presence of a governor and its function. If skeletal
      muscle anaerobiosis is the protected variable then, under conditions in which
      arterial oxygen content is reduced, maximal exercise should terminate with peak
      cardiovascular function to ensure maximum delivery of oxygen to the active
      muscle. In contrast, if the function of the heart or some other oxygen-sensitive
      organ is to be protected, then peak cardiovascular function will be higher during
      hyperoxia and reduced during hypoxia compared with normoxia. This paper reviews
      the evidence that peak cardiovascular function is reduced during maximal exercise
      in both acute and chronic hypoxia with no evidence for any primary alterations in
      myocardial function. Since peak skeletal muscle electromyographic activity is
      also reduced during hypoxia, these data support a model in which a central,
      neural governor constrains the cardiac output by regulating the mass of skeletal
      muscle that can be activated during maximal exercise in both acute and chronic
      hypoxia.

PMID- 11581339
TI  - Limits to human locomotor performance: phylogenetic origins and comparative
      perspectives.
AB  - Studies of human exercise physiology have been conducted from a largely
      ahistorical perspective. This approach usefully elucidates proximate limits to
      locomotor performance, but ignores potential sources of biomechanical and
      physiological variation that derive from adaptation to ancestral environments.
      Phylogenetic reconstruction suggests that multiple hominoid lineages, including
      that leading to Homo sapiens, evolved in African highlands at altitudes of 1000
      2000 m. The evolution of human locomotor physiology therefore occurred under
      conditions of hypobaric hypoxia. In contrast to present-day humans running on
      treadmills or exercising in otherwise rectilinear trajectories, ancestral
      patterns of hominid locomotion probably involved intermittent knuckle-walking
      over variable terrain, occasional bouts of arboreality and an evolving capacity
      for bipedalism. All such factors represent potential axes of locomotor variation
      at present unstudied in extant hominoid taxa. As with humans, hummingbirds
      evolved in mid-montane contexts but pose an extreme contrast with respect to body
      size, locomotor mode and metabolic capacity. Substantial biomechanical and
      physiological challenges are associated with flight in hypobaria. Nonetheless,
      hummingbird lineages demonstrate a progressive invasion of higher elevations and
      a remarkable tolerance to hypoxia during hovering. Upregulation of aerobic
      capacity and parallel resistance to hypoxia may represent coupled evolutionary
      adaptations to flight under high-altitude conditions.

PMID- 11581340
TI  - What's to be done about racism in medicine?

PMID- 11581341
TI  - Oesophageal cancer surgery.

PMID- 11581343
TI  - Requests for vasectomy: counselling and consent.

PMID- 11581342
TI  - Screening for diabetes in pregnancy.

PMID- 11581344
TI  - Nephrotoxicity in the elderly due to co-prescription of angiotensin converting
      enzyme inhibitors and nonsteroidal anti-inflammatory drugs.
AB  - Both angiotensin converting enzyme inhibitors and nonsteroidal anti-inflammatory
      drugs can lead to functional renal insufficiency. In an observational study we
      assessed the frequency of this adverse effect in patients aged over 75 years
      receiving these drugs in combination. In one year, out of 1500 patients whose
      records were screened, 12 were prescribed this combination. 2 developed acute
      renal failure, of whom one died and the other recovered after discontinuation of
      both drugs. 4 patients showed deterioration in renal function, which returned to
      normal after one of the drugs was stopped. Renal function remained stable in 6
      patients: patients with deterioration in renal function were older and more
      likely to be on diuretics. This drug combination is commonly nephrotoxic in the
      elderly and should be avoided, especially in those taking diuretics.

PMID- 11581345
TI  - 'Where shall we send our paper?' A simple decision tool for joint authors.

PMID- 11581346
TI  - Students sitting medical finals--ready to be house officers?
AB  - An initial survey of students approaching qualification and the preregistration
      house officer year revealed anxiety about competence in several important
      clinical skills. A questionnaire study was then undertaken to assess, first, the
      extent to which students had attained the skills required for the preregistration
      year and, second, the amount of training in these skills provided during the
      preregistration year. 122 medical students taking their final examinations were
      asked about training and practice in eight core clinical skills, and 84 graduates
      from the same school, approaching the end of their preregistration year, were
      asked about postgraduate training in these skills. The response rate of each
      group was 100%. Of the eight skills studied, most had been performed few times by
      the students at qualification. Less than half the current preregistration house
      officers could recall training being given in any of the skills studied. There
      were no significant differences in house-officer training between teaching
      hospitals and district general hospitals. Regarding needlestick injuries, nearly
      two-thirds of preregistration house officers were unable to recall any training
      at either undergraduate or postgraduate level. These results suggest that
      training in clinical skills can be improved. Training is already changing with
      use of clinical skills laboratories and logbooks. We also recommend mandatory
      needlestick training both in undergraduate programmes and in induction courses
      for preregistration house officers.

PMID- 11581347
TI  - Myalgia with lymphadenopathy.

PMID- 11581348
TI  - Giant vaginal stone with embedded contraceptive device.

PMID- 11581349
TI  - Primary pulmonary hypertension in pregnancy.

PMID- 11581350
TI  - Vomiting with depression: choroid plexus papilloma.

PMID- 11581351
TI  - Splenic rupture after vomiting.

PMID- 11581352
TI  - Spirituality in medicine: what is to be done?

PMID- 11581353
TI  - Fitness standards for the transport industries.

PMID- 11581354
TI  - Pickles of Wensleydale.

PMID- 11581355
TI  - The transformation of medicine by the magic of music in the romances of
      Shakespeare.

PMID- 11581356
TI  - Evidence-based art?

PMID- 11581357
TI  - Evidence-based art?

PMID- 11581358
TI  - London medical schools.

PMID- 11581359
TI  - Thyrotoxicosis with heart block.

PMID- 11581360
TI  - Carbon monoxide poisoning.

PMID- 11581361
TI  - Adverse events in hospital practice.

PMID- 11581362
TI  - The Mozart effect.

PMID- 11581363
TI  - Leechcraft.

PMID- 11581364
TI  - Transition from paediatric clinic to the adult service.

PMID- 11581365
TI  - Filmless images for radiology teaching.

PMID- 11581366
TI  - Crutch walker's shoulder.

PMID- 11581367
TI  - John Hunter's health.

PMID- 11581368
TI  - Attitudes to adhesion.

PMID- 11581370
TI  - Kilham polyomavirus: activation of gene expression and DNA replication in mouse
      fibroblast cells by an enhancer substitution.
AB  - The Kilham strain of polyomavirus (KV) infects vascular endothelial cells in vivo
      (J. E. Greenlee, Infect. Immun. 26:705-713, 1979), but no permissive cell type
      for growth of the virus in vitro has been identified. The failure of KV DNA to
      replicate in mouse fibroblast cells after transfection suggested that viral gene
      expression had narrow cell specificity. A KV substitution mutant having a part of
      the regulatory region of KV DNA replaced with a segment of the polyomavirus
      transcriptional enhancer was constructed. The substitution mutant was able to
      replicate in transfected 3T3 cells, and the newly replicated viral DNA associated
      with protein to form particles with the density of virions in CsCl equilibrium
      gradients. However, these particles were noninfectious when tested on 3T3 cells,
      suggesting that absorption or uptake of virus particles was defective for these
      cells. Analysis of early and late promoter activities by luciferase reporter gene
      expression showed that the enhancer substitution had a moderate positive effect
      on early gene expression and a large effect on the expression of the late genes.
      KV large T antigen inhibited the activities of both the wild-type and the
      substitution mutant early promoter, whereas only the mutant late promoter was
      activated under the same conditions. A comparison of the KV and polyomavirus
      large T antigens showed that they were not interchangeable in the initiation of
      KV and polyomavirus DNA synthesis. Furthermore, the wild-type KV origin of DNA
      replication was less active than the mutant structure in the presence of
      saturating amounts of KV large T antigen. Together, our data demonstrate several
      differences between the two types of large T antigen in their interactions with
      cellular proteins.

PMID- 11581371
TI  - Deletion of beta-strand and alpha-helix secondary structure in normal prion
      protein inhibits formation of its protease-resistant isoform.
AB  - A fundamental event in the pathogenesis of transmissible spongiform
      encephalopathies (TSE) is the conversion of a normal, proteinase K-sensitive,
      host-encoded protein, PrP-sen, into its protease-resistant isoform, PrP-res.
      During the formation of PrP-res, PrP-sen undergoes conformational changes that
      involve an increase of beta-sheet secondary structure. While previous studies in
      which PrP-sen deletion mutants were expressed in transgenic mice or scrapie
      infected cell cultures have identified regions in PrP-sen that are important in
      the formation of PrP-res, the exact role of PrP-sen secondary structures in the
      conformational transition of PrP-sen to PrP-res has not yet been defined. We
      constructed PrP-sen mutants with deletions of the first beta-strand, the second
      beta-strand, or the first alpha-helix and tested whether these mutants could be
      converted to PrP-res in both scrapie-infected neuroblastoma cells (Sc(+)-MNB
      cells) and a cell-free conversion assay. Removal of the second beta-strand or the
      first alpha-helix significantly altered both processing and the cellular
      localization of PrP-sen, while deletion of the first beta-strand had no effect on
      these events. However, all of the mutants significantly inhibited the formation
      of PrP-res in Sc(+)-MNB cells and had a greatly reduced ability to form protease
      resistant PrP in a cell-free assay system. Thus, our results demonstrate that
      deletion of the beta-strands and the first alpha-helix of PrP-sen can
      fundamentally affect PrP-res formation and/or PrP-sen processing.

PMID- 11581372
TI  - Adenovirus DNA binding protein interacts with the SNF2-related CBP activator
      protein (SrCap) and inhibits SrCap-mediated transcription.
AB  - The SNF2-related CBP activator protein, SrCap (pronounced "sir cap"), shares
      homology with the SNF2/SWI2 protein family. SrCap was cloned through its ability
      to bind CBP. SrCap can function as a CBP coactivator and can activate
      transcription in a reporter assay when expressed as a Gal-SrCap fusion protein. A
      monoclonal antibody raised against the carboxyl terminus of SrCap
      coimmunoprecipitates CBP/p300, supporting the model that SrCap is a CBP binding
      protein and that these proteins can be found together in a cellular protein
      complex. In addition, several cellular proteins are coimmunoprecipitated by the
      SrCap-specific antibody. Since adenovirus E1A proteins interact with CBP/p300
      proteins, we examined what proteins could be copurified in a SrCap-specific
      coimmunoprecipitation assay from lysates of adenovirus-infected cells. While E1A
      proteins were not detected in this complex, to our surprise, we observed the
      presence of an infected-cell-specific band of 72 kDa, which we suspected might be
      the adenovirus DNA binding protein, DBP. The adenovirus DBP is a multifunctional
      protein involved in several aspects of the adenovirus life cycle, including an
      ability to modulate transcription. The identity of DBP was confirmed by DBP
      specific Western blot analysis and by reimmunoprecipitating DBP from denatured
      SrCap-specific protein complexes. Using in vitro-translated DBP and SrCap
      proteins, we demonstrated that these proteins interact. To determine whether this
      interaction could affect SrCap-mediated transcription, we tested whether
      increasing amounts of DBP could modulate the Gal-SrCap transcription activity. We
      observed that DBP inhibited Gal-SrCap transcription activity in a dose-dependent
      manner. These data suggest a novel mechanism of adenovirus host cell control by
      which DBP binds to and inactivates SrCap, a member of the SNF2 chromatin
      remodeling protein family.

PMID- 11581373
TI  - Overexpression of the adenovirus type 12 (Ad12) pTP or E1A gene facilitates Ad12
      DNA replication in nonpermissive BHK21 hamster cells.
AB  - In the adenovirus type 12 (Ad12) hamster cell system, abortive virus infection is
      one of the factors associated with the highly efficient oncogenesis in newborn
      Syrian hamsters. We have shown earlier that the replication and efficient late
      transcription of the Ad12 genome are blocked in Syrian hamster cells. Some of the
      early Ad12 functions are transcribed in these cells, although at a minimal rate.
      In the present study, we demonstrate that low expression levels of the E1A and
      precursor to terminal protein (pTP) genes of Ad12 seem to be responsible for the
      lack of Ad12 DNA replication in hamster cells. The Ad12 genes for the E1A
      functions or for pTP were tethered to the strong early promoter of the human
      cytomegalovirus and transfected into BHK21 cells. Subsequently, these cells were
      infected with Ad12 virions. In Ad12-infected BHK21 cells, which overexpressed pTP
      or E1A, full-length Ad12 DNA was de novo synthesized, as documented by metabolic
      labeling with [3H]thymidine and by zone velocity sedimentation in alkaline
      sucrose gradients followed by gel electrophoresis of the 3H-labeled DNA and
      Southern blot hybridization to 32P-labeled Ad12 DNA. Transfection of the cloned
      E1A region of Ad2 yielded similar results. The newly synthesized Ad12 DNA was
      covalently linked to pTP. The Ad12 DNA binding protein (DBP) and DNA polymerase
      (pol) genes were transcribed at levels similar to those in merely Ad12-infected
      cells. In pTP or E1A gene-transfected and Ad12-infected BHK21 cells, marginal
      levels of late Ad12 mRNA were detectable. Late Ad12 proteins were, however, not
      synthesized. Apparently, Ad12 DNA replication in hamster cells is rendered
      impossible due to insufficient threshold levels of the viral E1A and/or pTP.

PMID- 11581374
TI  - Glycoprotein D-independent infectivity of pseudorabies virus results in an
      alteration of in vivo host range and correlates with mutations in glycoproteins B
      and H.
AB  - Infection of cells by herpesviruses is initiated by the interaction of viral
      envelope glycoproteins with cellular receptors. In the alphaherpesvirus
      pseudorabies virus (PrV), the causative agent of Aujeszky's disease in pigs, the
      essential glycoprotein D (gD) mediates secondary attachment of virions to target
      cells by binding to newly identified cellular receptors (R. J. Geraghty, C.
      Krummenacher, G. H. Cohen, R. J. Eisenberg, and P. G. Spear, Science 280:1618
      1620, 1998). However, in the presence of compensatory mutations, infection can
      also occur in the absence of gD, as evidenced by the isolation in cell culture of
      an infectious gD-negative PrV mutant (PrV-gD(-) Pass) (J. Schmidt, B. G. Klupp,
      A. Karger, and T. C. Mettenleiter, J. Virol. 71:17-24, 1997). PrV-gD(-) Pass is
      replication competent with an only moderate reduction in specific infectivity but
      appears to bind to receptors different from those recognized by wild-type PrV (A.
      Karger, J. Schmidt, and T. C. Mettenleiter, J. Virol. 72:7341-7348, 1998). To
      analyze whether this alteration in receptor usage in vitro influences infection
      in vivo, the model host mouse and the natural host pig were intranasally infected
      with PrV-gD(-) Pass and were compared to animals infected by wild-type PrV. For
      mice, a comparable progress of disease was observed, and all animals infected
      with mutant virus died, although they exhibited a slight delay in the onset of
      symptoms and, correspondingly, a longer time to death. In contrast, whereas wild
      type PrV-infected pigs showed clinical signs and histological and
      histopathological findings typical of PrV infection, no signs of disease were
      observed after infection with PrV-gD(-) Pass. Moreover, in these animals, virus
      infected cells were not detectable by immunohistochemical staining of different
      organ samples and no virus could be isolated from nasal swabs. Mutations in
      glycoproteins B and H were found to correlate with, and probably contribute to,
      gD-independent infectivity. In conclusion, although PrV-gD(-) Pass is virulent in
      mice, it is apparently unable to infect the natural host, the pig. This altered
      host range in vivo correlates with a difference of receptor usage in vitro and
      demonstrates for the first time the importance of gD receptors in
      alphaherpesvirus infection of an animal host.

PMID- 11581375
TI  - A novel CD8-independent high-avidity cytotoxic T-lymphocyte response directed
      against an epitope in the phosphoprotein of the paramyxovirus simian virus 5.
AB  - Adoptive transfer studies have shown that cytotoxic T lymphocytes (CTL) of high
      avidity, capable of recognizing low levels of peptide-MHC I molecules, are more
      efficient at reducing viral titers than are low-avidity CTL, thus establishing
      CTL avidity as a critical parameter for the ability of a CTL to clear virus in
      vivo. It has been well documented that CTL of high avidity are relatively CD8
      independent, whereas low-avidity CTL require CD8 engagement in order to become
      activated. In this study we have analyzed the antiviral CTL response elicited
      following infection with the paramyxovirus simian virus 5 (SV5). We have
      identified the immunodominant and subdominant CTL responses and subsequently
      assessed the avidity of these responses by their CD8 dependence. This is the
      first study in which the relationship between immunodominance and CTL avidity has
      been investigated. The immunodominant response was directed against an epitope
      present in the viral M protein, and subdominant responses were directed against
      epitopes present in the P, F, and HN proteins. Similarly to other CTL responses
      we have analyzed, the immunodominant response and the subdominant F and HN
      responses were comprised of both high- and low-avidity CTL. However, the
      subdominant response directed against the epitope present in the P protein is
      novel, as it is exclusively high avidity. This high-avidity response is
      independent of both the route of infection and expression by recombinant SV5. A
      further understanding of the inherent properties of P that elicit only high
      avidity CTL may allow for the design of more efficacious vaccine vectors that
      preferentially elicit high-avidity CTL in vivo.

PMID- 11581377
TI  - Vaccinia virus telomeres: interaction with the viral I1, I6, and K4 proteins.
AB  - The 192-kb linear DNA genome of vaccinia virus has covalently closed hairpin
      termini that are extremely AT rich and contain 12 extrahelical bases. Vaccinia
      virus telomeres have previously been implicated in the initiation of viral genome
      replication; therefore, we sought to determine whether the telomeres form
      specific protein-DNA complexes. Using an electrophoretic mobility shift assay, we
      found that extracts prepared from virions and from the cytoplasm of infected
      cells contain telomere binding activity. Four shifted complexes were detected
      using hairpin probes representing the viral termini, two of which represent an
      interaction with the "flip" isoform and two with the "flop" isoform. All of the
      specificity for protein binding lies within the terminal 65-bp hairpin sequence.
      Viral hairpins lacking extrahelical bases cannot form the shifted complexes,
      suggesting that DNA structure is crucial for complex formation. Using an affinity
      purification protocol, we purified the proteins responsible for hairpin-protein
      complex formation. The vaccinia virus I1 protein was identified as being
      necessary and sufficient for the formation of the upper doublet of shifted
      complexes, and the vaccinia virus I6 protein was shown to form the lower doublet
      of shifted complexes. Competition and challenge experiments confirmed that the
      previously uncharacterized I6 protein binds tightly and with great specificity to
      the hairpin form of the viral telomeric sequence. Incubation of viral hairpins
      with extracts from infected cells also generates a smaller DNA fragment that is
      likely to reflect specific nicking at the apex of the hairpin; we show that the
      vaccinia virus K4 protein is necessary and sufficient for this reaction. We
      hypothesize that these telomere binding proteins may play a role in the
      initiation of vaccinia virus genome replication and/or genome encapsidation.

PMID- 11581376
TI  - Macrophage tropism of human immunodeficiency virus type 1 isolates from brain and
      lymphoid tissues predicts neurotropism independent of coreceptor specificity.
AB  - The viral determinants that underlie human immunodeficiency virus type 1 (HIV-1)
      neurotropism are unknown, due in part to limited studies on viruses isolated from
      brain. Previous studies suggest that brain-derived viruses are macrophage tropic
      (M-tropic) and principally use CCR5 for virus entry. To better understand HIV-1
      neurotropism, we isolated primary viruses from autopsy brain, cerebral spinal
      fluid, blood, spleen, and lymph node samples from AIDS patients with dementia and
      HIV-1 encephalitis. Isolates were characterized to determine coreceptor usage and
      replication capacity in peripheral blood mononuclear cells (PBMC), monocyte
      derived macrophages (MDM), and microglia. Env V1/V2 and V3 heteroduplex tracking
      assay and sequence analyses were performed to characterize distinct variants in
      viral quasispecies. Viruses isolated from brain, which consisted of variants that
      were distinct from those in lymphoid tissues, used CCR5 (R5), CXCR4 (X4), or both
      coreceptors (R5X4). Minor usage of CCR2b, CCR3, CCR8, and Apj was also observed.
      Primary brain and lymphoid isolates that replicated to high levels in MDM showed
      a similar capacity to replicate in microglia. Six of 11 R5 isolates that
      replicated efficiently in PBMC could not replicate in MDM or microglia due to a
      block in virus entry. CD4 overexpression in microglia transduced with retroviral
      vectors had no effect on the restricted replication of these virus strains.
      Furthermore, infection of transfected cells expressing different amounts of CD4
      or CCR5 with M-tropic and non-M-tropic R5 isolates revealed a similar dependence
      on CD4 and CCR5 levels for entry, suggesting that the entry block was not due to
      low levels of either receptor. Studies using TAK-779 and AMD3100 showed that two
      highly M-tropic isolates entered microglia primarily via CXCR4. These results
      suggest that HIV-1 tropism for macrophages and microglia is restricted at the
      entry level by a mechanism independent of coreceptor specificity. These findings
      provide evidence that M-tropism rather than CCR5 usage predicts HIV-1
      neurotropism.

PMID- 11581378
TI  - Long-term subclinical carrier state precedes scrapie replication and adaptation
      in a resistant species: analogies to bovine spongiform encephalopathy and variant
      Creutzfeldt-Jakob disease in humans.
AB  - Cattle infected with bovine spongiform encephalopathy (BSE) appear to be a
      reservoir for transmission of variant Creutzfeldt-Jakob disease (vCJD) to humans.
      Although just over 100 people have developed clinical vCJD, millions have
      probably been exposed to the infectivity by consumption of BSE-infected beef. It
      is currently not known whether some of these individuals will develop disease
      themselves or act as asymptomatic carriers of infectivity which might infect
      others in the future. We have studied agent persistence and adaptation after
      cross-species infection using a model of mice inoculated with hamster scrapie
      strain 263K. Although mice inoculated with hamster scrapie do not develop
      clinical disease after inoculation with 10 million hamster infectious doses,
      hamster scrapie infectivity persists in brain and spleen for the life span of the
      mice. In the present study, we were surprised to find a 1-year period
      postinfection with hamster scrapie where there was no evidence for replication of
      infectivity in mouse brain. In contrast, this period of inactive persistence was
      followed by a period of active replication of infectivity as well as adaptation
      of new strains of agent capable of causing disease in mice. In most mice, neither
      the early persistent phase nor the later replicative phase could be detected by
      immunoblot assay for protease-resistant prion protein (PrP). If similar
      asymptomatic carriers of infection arise after exposure of humans or animals to
      BSE, this could markedly increase the danger of additional spread of BSE or vCJD
      infection by contaminated blood, surgical instruments, or meat. If such
      subclinical carriers were negative for protease-resistant PrP, similar to our
      mice, then the recently proposed screening of brain, tonsils, or other tissues of
      animals and humans by present methods such as immunoblotting or
      immunohistochemistry might be too insensitive to identify these individuals.

PMID- 11581379
TI  - CD4 down-modulation by human immunodeficiency virus type 1 Nef correlates with
      the efficiency of viral replication and with CD4(+) T-cell depletion in human
      lymphoid tissue ex vivo.
AB  - The human immunodeficiency virus type 1 (HIV-1) Nef protein is an important
      virulence factor. Nef has several functions, including down-modulation of CD4 and
      class I major histocompatibility complex cell surface expression, enhancement of
      virion infectivity, and stimulation of viral replication in peripheral blood
      mononuclear cells. Nef also increases HIV-1 replication in human lymphoid tissue
      (HLT) ex vivo. We analyzed recombinant and primary nef alleles with highly
      divergent activity in different in vitro assays to clarify which of these Nef
      activities are functionally linked. Our results demonstrate that Nef activity in
      CD4 down-regulation correlates significantly with the efficiency of HIV-1
      replication and with the severity of CD4(+) T-cell depletion in HLT. In
      conclusion, HIV-1 Nef variants with increased activity in CD4 down-modulation
      would cause severe depletion of CD4(+) T cells in lymphoid tissues and accelerate
      AIDS progression.

PMID- 11581381
TI  - Requirements for minus-strand transfer catalyzed by Rous sarcoma virus reverse
      transcriptase.
AB  - We have examined the specific minus-strand transfer reactions that occur after
      the synthesis of minus strong-stop DNA and nonspecific strand switching on
      homopolymeric poly(rA) templates with different types of Rous sarcoma virus (RSV)
      reverse transcriptases. Three different types of reverse transcriptases can be
      isolated from virions of RSV: heterodimeric alphabeta and homodimeric alpha and
      beta. The mechanism of minus-strand transfer was examined using a model primer
      template substrate corresponding to the 5'- and 3'-terminal RNA regions of the
      RSV genome. The results reveal that the RNase H activity of RSV reverse
      transcriptases is required for minus-strand transfer. Less than 2% of strand
      transfer of the extended product is detectable with RNase H-deficient enzymes. We
      could show that the alpha homodimer lacking the integrase domain can perform
      strand transfer almost as efficiently as the alphabeta and alphaPol heterodimers.
      In contrast, the activities of beta and Pol for minus-strand transfer are
      reduced. Furthermore, a two- to fivefold increase in minus-strand transfer
      activities was observed in the presence of human immunodeficiency virus type 1
      nucleocapsid protein.

PMID- 11581380
TI  - Evolutionary relationships and systematics of the alphaviruses.
AB  - Partial E1 envelope glycoprotein gene sequences and complete structural
      polyprotein sequences were used to compare divergence and construct phylogenetic
      trees for the genus Alphavirus. Tree topologies indicated that the mosquito-borne
      alphaviruses could have arisen in either the Old or the New World, with at least
      two transoceanic introductions to account for their current distribution. The
      time frame for alphavirus diversification could not be estimated because maximum
      likelihood analyses indicated that the nucleotide substitution rate varies
      considerably across sites within the genome. While most trees showed evolutionary
      relationships consistent with current antigenic complexes and species, several
      changes to the current classification are proposed. The recently identified fish
      alphaviruses salmon pancreas disease virus and sleeping disease virus appear to
      be variants or subtypes of a new alphavirus species. Southern elephant seal virus
      is also a new alphavirus distantly related to all of the others analyzed. Tonate
      virus and Venezuelan equine encephalitis virus strain 78V3531 also appear to be
      distinct alphavirus species based on genetic, antigenic, and ecological criteria.
      Trocara virus, isolated from mosquitoes in Brazil and Peru, also represents a new
      species and probably a new alphavirus complex.

PMID- 11581382
TI  - Papillomavirus pseudovirus: a novel vaccine to induce mucosal and systemic
      cytotoxic T-lymphocyte responses.
AB  - Intestinal mucosa is a portal for many infectious pathogens. Systemic
      immunization, in general, does not induce a cytotoxic T-lymphocyte (CTL) response
      at the mucosal surface. Because papillomavirus (PV) naturally infects mucosa and
      skin, we determined whether PV pseudovirus, i.e., PV-like particles in which
      unrelated DNA plasmids are packaged, could generate specific mucosal immunity. We
      found that the pseudovirus that encoded the lymphocytic choriomeningitis virus
      gp33 epitope induced a stronger CTL response than a DNA vaccine (plasmid)
      encoding the same epitope given systemically. The virus-like particles that were
      used to make the pseudoviruses provided an adjuvant effect for induction of CTLs
      by the DNA vaccine. The PV pseudovirus pseudoinfected mucosal and systemic
      lymphoid tissues when administered orally. Oral immunization with the pseudovirus
      encoding human PV type 16 mutant E7 induced mucosal and systemic CTL responses.
      In comparison, a DNA vaccine encoding E7, when given orally, did not induce a CTL
      response in intestinal mucosal lymphoid tissue. Further, oral immunization with
      the human PV pseudovirus encoding E7 protected mice against mucosal challenge
      with an E7-expressing bovine PV pseudovirus. Thus, PV pseudovirus can be used as
      a novel vaccine to induce mucosal and systemic CTL responses.

PMID- 11581383
TI  - The R3 region, one of three major repetitive regions of human herpesvirus 6, is a
      strong enhancer of immediate-early gene U95.
AB  - An immediate-early (IE) gene of human herpesvirus 6 (HHV-6), U95, has similarity
      at the amino acid level to the murine cytomegalovirus (MCMV) IE2 gene and is
      related to the human cytomegalovirus (HCMV) US22 gene family. Sequence analyses
      of U95 cDNA clones revealed that the transcription start site was located about
      1.6 kbp upstream of the putative initiating ATG and that the transcript consisted
      of two exons. A single intron extended from nucleotides 142589 to 144229, which
      contained ORF U94. A protein with a molecular mass of about 120 kDa was
      translated from this cDNA clone in an in vitro transcription-translation assay.
      The transcription start site was found to be 220 bp downstream of the R3 region
      by primer extension analysis. HHV-6 has three repetitive elements, R1, R2, and
      R3, in or near the IE-A locus. R3 is composed of 24 copies of a 104- to 107-bp
      sequence element, which contains multiple putative binding sites for cellular
      transcription factors such as AP2 and NF-kappaB, and its biological significance
      has yet to be elucidated. The region between -710 and +46 relative to the
      transcription start site of U95 was analyzed in this study. Deletion from -710 to
      -396, corresponding to three copies of an R3 unit, decreased the promoter
      activity by 15-fold, and coexpression of IkappaBalpha(S32A/S36A) repressed it to
      almost the same level. Electrophoretic mobility shift assays showed that NF
      kappaB family members p50 and c-Rel bound to NF-kappaB sites derived from the R3
      region. These results demonstrate that R3 strongly enhances the U95 promoter
      activity and that NF-kappaB and binding sites for NF-kappaB in the R3 region play
      an important role in its activation. Because U95 promoter activity correlated
      with the number of R3 units, which each contained an NF-kappaB site, the
      repetitive organization of R3 is important for regulating U95 transcription.

PMID- 11581384
TI  - Host RNA polymerase requirements for transcription of the human hepatitis delta
      virus genome.
AB  - Replication of the genome of hepatitis delta virus (HDV) requires RNA-directed
      RNA synthesis using a host polymerase(s). This manuscript reviews the relevant
      published evidence. It also provides two new studies, both of which made use of
      transiently transfected Huh7 cells undergoing HDV RNA-directed RNA synthesis. For
      the first study, RNA transcription inhibitors were added to the transfected cells
      for periods of 1 to 2 days, after which assays of the effects on the accumulation
      of processed unit-length genomic HDV RNA were performed. For the second study,
      nuclei were isolated at 6 days after transfection, and then in vitro runoff
      transcription was used to assay the effects of RNA transcription inhibitors.
      Overall, the data support the interpretation that HDV transcription does not
      require host polymerase I or III (pol I or III) but at least primarily involves
      an enzyme resembling pol II.

PMID- 11581385
TI  - Virus-cell interactions regulating induction of tumor necrosis factor alpha
      production in macrophages infected with herpes simplex virus.
AB  - Macrophages respond to virus infections by rapidly secreting proinflammatory
      cytokines, which play an important role in the first line of defense. Tumor
      necrosis factor alpha (TNF-alpha) is one of the major macrophage-produced
      cytokines. In this study we have investigated the virus-cell interactions
      responsible for induction of TNF-alpha expression in herpes simplex virus (HSV)
      infected macrophages. Both HSV type 1 (HSV-1) and HSV-2 induced TNF-alpha
      expression in macrophages activated with gamma interferon (IFN-gamma). This
      induction was to some extent sensitive to UV treatment of the virus. Virus
      particles unable to enter the cells displayed reduced capacity to stimulate TNF
      alpha expression but retained a significant portion which was abolished by HSV
      specific antibodies. Recombinant HSV-1 glycoprotein D was able to trigger TNF
      alpha secretion in concert with IFN-gamma. Sugar moieties of HSV glycoproteins
      have been reported to be involved in induction of IFN-alpha but did not
      contribute to TNF-alpha expression in macrophages. Moreover, the entry-dependent
      portion of the TNF-alpha induction was investigated with HSV-1 mutants and found
      to be independent of the tegument proteins VP16 and UL13 and partly dependent on
      nuclear translocation of the viral DNA. Finally, we found that macrophages
      expressing an inactive mutant of the double-stranded RNA (dsRNA)-activated
      protein kinase (PKR) produced less TNF-alpha in response to infectious HSV
      infection than the empty-vector control cell line but displayed the same
      responsiveness to UV-inactivated virus. These results indicate that HSV induces
      TNF-alpha expression in macrophages through mechanisms involving (i) viral
      glycoproteins, (ii) early postentry events occurring prior to nuclear
      translocation of viral DNA, and (iii) viral dsRNA-PKR.

PMID- 11581386
TI  - A commonly recognized simian immunodeficiency virus Nef epitope presented to
      cytotoxic T lymphocytes of Indian-origin rhesus monkeys by the prevalent major
      histocompatibility complex class I allele Mamu-A*02.
AB  - The ability to monitor vaccine-elicited CD8(+) cytotoxic T-lymphocyte (CTL)
      responses in simian immunodeficiency virus (SIV)- and simian-human
      immunodeficiency virus (SHIV)-infected rhesus monkeys has been limited by our
      knowledge of viral epitopes predictably presented to those lymphocytes by common
      rhesus monkey MHC class I alleles. We now define an SIV and SHIV Nef CTL epitope
      (YTSGPGIRY) that is presented to CD8(+) T lymphocytes by the common rhesus monkey
      MHC class I molecule Mamu-A*02. All seven infected Mamu-A*02(+) monkeys evaluated
      demonstrated this response, and peptide-stimulated interferon gamma Elispot
      assays indicated that the response represents a large proportion of the entire
      CD8(+) T-lymphocyte SIV- or SHIV-specific immune response of these animals.
      Knowledge of this epitope and MHC class I allele substantially increases the
      number of available rhesus monkeys that can be used for testing prototype HIV
      vaccines in this important animal model.

PMID- 11581387
TI  - Role of CD8(+) lymphocytes in control of simian immunodeficiency virus infection
      and resistance to rechallenge after transient early antiretroviral treatment.
AB  - Transient antiretroviral treatment with tenofovir, (R)-9-(2
      phosphonylmethoxypropyl)adenine, begun shortly after inoculation of rhesus
      macaques with the highly pathogenic simian immunodeficiency virus (SIV) isolate
      SIVsmE660, facilitated the development of SIV-specific lymphoproliferative
      responses and sustained effective control of the infection following drug
      discontinuation. Animals that controlled plasma viremia following transient
      postinoculation treatment showed substantial resistance to subsequent intravenous
      rechallenge with homologous (SIVsmE660) and highly heterologous (SIVmac239) SIV
      isolates, up to more than 1 year later, despite the absence of measurable
      neutralizing antibody. In some instances, resistance to rechallenge was observed
      despite the absence of detectable SIV-specific binding antibody and in the face
      of SIV lymphoproliferative responses that were low or undetectable at the time of
      challenge. In vivo monoclonal antibody depletion experiments demonstrated a
      critical role for CD8(+) lymphocytes in the control of viral replication; plasma
      viremia rose by as much as five log units after depletion of CD8(+) cells and
      returned to predepletion levels (as low as <100 copy Eq/ml) as circulating CD8(+)
      cells were restored. The extent of host control of replication of highly
      pathogenic SIV strains and the level of resistance to heterologous rechallenge
      achieved following transient postinoculation treatment compared favorably to the
      results seen after SIVsmE660 and SIVmac239 challenge with many vaccine
      strategies. This impressive control of viral replication was observed despite
      comparatively modest measured immune responses, less than those often achieved
      with vaccination regimens. The results help establish the underlying feasibility
      of efforts to develop vaccines for the prevention of AIDS, although the exact
      nature of the protective host responses involved remains to be elucidated.

PMID- 11581388
TI  - Neutralizing antibodies associated with viremia control in a subset of
      individuals after treatment of acute human immunodeficiency virus type 1
      infection.
AB  - Immediate treatment of acute human immunodeficiency virus type 1 (HIV-1)
      infection has been associated with subsequent control of viremia in a subset of
      patients after therapy cessation, but the immune responses contributing to
      control have not been fully defined. Here we examined neutralizing antibodies as
      a correlate of viremia control following treatment interruption in HIV-1-infected
      individuals in whom highly active antiretriviral therapy (HAART) was initiated
      during early seroconversion and who remained on therapy for 1 to 3 years.
      Immediately following treatment interruption, neutralizing antibodies were
      undetectable with T-cell-line adapted strains and the autologous primary HIV-1
      isolate in seven of nine subjects. Env- and Gag-specific antibodies as measured
      by enzyme-linked immunosorbent assay were also low or undetectable at this time.
      Despite this apparent poor maturation of the virus-specific B-cell response
      during HAART, autologous neutralizing antibodies emerged rapidly and correlated
      with a spontaneous downregulation in rebound viremia following treatment
      interruption in three subjects. Control of rebound viremia was seen in other
      subjects in the absence of detectable neutralizing antibodies. The results
      indicate that virus-specific B-cell priming occurs despite the early institution
      of HAART, allowing rapid secondary neutralizing-antibody production following
      treatment interruption in a subset of individuals. Since early HAART limits viral
      diversification, we hypothesize that potent neutralizing-antibody responses to
      autologous virus are able to mature and that in some persons these responses
      contribute to the control of plasma viremia after treatment cessation.

PMID- 11581389
TI  - Hemagglutinin 1-specific immunoglobulin G and Fab molecules mediate
      postattachment neutralization of influenza A virus by inhibition of an early
      fusion event.
AB  - In standard neutralization (STAN), virus and antibody are reacted together before
      inoculation of target cells, and inhibition of almost any of the processes
      concerned in the early interaction of virus and cell, including inhibition of
      virus attachment to cell receptors, can be the cause of neutralization by a
      particular monoclonal antibody (MAb). To simplify the interpretation of antibody
      action, we carried out a study of postattachment neutralization (PAN), where
      virus is allowed to attach to target cells before neutralizing antibody is
      introduced. We used influenza virus A/PR/8/34 (H1N1) and monoclonal
      immunoglobulin G (IgG) molecules and their Fabs specific to antigenic sites Sb
      (tip), Ca2 (loop), and Cb (hinge) of the hemagglutinin 1 (HA1) protein. All IgGs
      and Fabs gave PAN, although with reduced efficiency compared with STAN. Thus,
      bivalent binding of antibody was not essential for PAN. By definition, none of
      these MAbs gave PAN by inhibiting virus attachment, and they did not elute
      attached virus from the target cell or inhibit endocytosis of virus. However,
      virus-cell fusion, as demonstrated by R18 fluorescence dequenching or hemolysis
      of red blood cells, was inhibited in direct proportion to neutralization and in a
      dose-dependent manner and was thus likely to be responsible for the observed
      neutralization. However, to get PAN, it was necessary to inhibit the activation
      of the prefusion intermediate, the earliest known form on the fusion pathway that
      is created when virus is incubated at pH 5 and 4 degrees C. PAN antibodies may
      act by binding HA trimers in contact with the cell and/or trimers in the
      immediate vicinity of the virus-cell contact point and so inhibit the recruitment
      of additional receptor-HA complexes.

PMID- 11581390
TI  - Mapping the sequences that mediate interaction of the equine herpesvirus 1
      immediate-early protein and human TFIIB.
AB  - The sole immediate-early (IE) gene of equine herpesvirus 1 encodes a 1,487-amino
      acid (aa) regulatory phosphoprotein that independently activates expression of
      early viral genes. Coimmunoprecipitation assays demonstrated that the IE protein
      physically interacts with the general transcription factor TFIIB. Using a variety
      of protein-binding assays that employed a panel of IE truncation and deletion
      mutants expressed as in vitro-synthesized or glutathione S-transferase fusion
      proteins, we mapped a TFIIB-binding domain to aa 407 to 757 of the IE protein. IE
      mutants carrying internal deletions of aa 426 to 578 and 621 to 757 were
      partially defective for TFIIB binding, indicating that aa 407 to 757 may harbor
      more than one TFIIB-binding domain. The interaction between the IE protein and
      TFIIB is of physiological importance, as evidenced by transient-cotransfection
      assays. Partial deletion of the TFIIB-binding domain within the IE protein
      inhibited its ability to activate expression of the viral thymidine kinase gene,
      a representative early promoter, and of the IR5 gene, a representative late
      promoter, by greater than 20 and 50%, respectively. These results indicate that
      the interaction of the IE protein with TFIIB is necessary for its full
      transactivation function and that the IE-TFIIB interaction may be part of the
      mechanism by which the IE protein activates transcription.

PMID- 11581391
TI  - Structure and temporal dynamics of populations within wheat streak mosaic virus
      isolates.
AB  - Variation within the Type and Sidney 81 strains of wheat streak mosaic virus was
      assessed by single-strand conformation polymorphism (SSCP) analysis and confirmed
      by nucleotide sequencing. Limiting-dilution subisolates (LDSIs) of each strain
      were evaluated for polymorphism in the P1, P3, NIa, and CP cistrons. Different
      SSCP patterns among LDSIs of a strain were associated with single-nucleotide
      substitutions. Sidney 81 LDSI-S10 was used as founding inoculum to establish
      three lineages each in wheat, corn, and barley. The P1, HC-Pro, P3, CI, NIa, NIb,
      and CP cistrons of LDSI-S10 and each lineage at passages 1, 3, 6, and 9 were
      evaluated for polymorphism. By passage 9, each lineage differed in consensus
      sequence from LDSI-S10. The majority of substitutions occurred within NIa and CP,
      although at least one change occurred in each cistron except HC-Pro and P3. Most
      consensus sequence changes among lineages were independent, with substitutions
      accumulating over time. However, LDSI-S10 bore a variant nucleotide (G(6016)) in
      NIa that was restored to A(6016) in eight of nine lineages by passage 6. This
      near-global reversion is most easily explained by selection. Examination of
      nonconsensus variation revealed a pool of unique substitutions (singletons) that
      remained constant in frequency during passage, regardless of the host species
      examined. These results suggest that mutations arising by viral polymerase error
      are generated at a constant rate but that most newly generated mutants are
      sequestered in virions and do not serve as replication templates. Thus, a
      substantial fraction of variation generated is static and has yet to be tested
      for relative fitness. In contrast, nonsingleton variation increased upon passage,
      suggesting that some mutants do serve as replication templates and may become
      established in a population. Replicated mutants may or may not rise to prominence
      to become the consensus sequence in a lineage, with the fate of any particular
      mutant subject to selection and stochastic processes such as genetic drift and
      population growth factors.

PMID- 11581392
TI  - The 5' untranslated region of Rhopalosiphum padi virus contains an internal
      ribosome entry site which functions efficiently in mammalian, plant, and insect
      translation systems.
AB  - Rhopalosiphum padi virus (RhPV) is one of several picorna-like viruses that
      infect insects; sequence analysis has revealed distinct differences between these
      agents and mammalian picornaviruses. RhPV has a single-stranded positive-sense
      RNA genome of about 10 kb; unlike the genomes of Picornaviridae, however, this
      genome contains two long open reading frames (ORFs). ORF1 encodes the virus
      nonstructural proteins, while the downstream ORF, ORF2, specifies the structural
      proteins. Both ORFs are preceded by long untranslated regions (UTRs). The
      intergenic UTR is known to contain an internal ribosome entry site (IRES) which
      directs non-AUG-initiated translation of ORF2. We have examined the 5' UTR of
      RhPV for IRES activity by translating synthetic dicistronic mRNAs containing this
      sequence in a variety of systems. We now report that the 5' UTR contains an
      element which directs internal initiation of protein synthesis from an AUG codon
      in mammalian, plant, and Drosophila in vitro translation systems. In contrast,
      the encephalomyocarditis virus IRES functions only in the mammalian system. The
      RhPV 5' IRES element has features in common with picornavirus IRES elements, in
      that no coding sequence is required for IRES function, but also with cellular
      IRES elements, as deletion analysis indicates that this IRES element does not
      have sharply defined boundaries.

PMID- 11581393
TI  - Rep-dependent initiation of adeno-associated virus type 2 DNA replication by a
      herpes simplex virus type 1 replication complex in a reconstituted system.
AB  - Productive infection by adeno-associated virus type 2 (AAV) requires coinfection
      with a helper virus, e.g., adenovirus or herpesviruses. In the case of adenovirus
      coinfection, the replication machinery of the host cell performs AAV DNA
      replication. In contrast, it has been proposed that the herpesvirus replication
      machinery might replicate AAV DNA. To investigate this question, we have
      attempted to reconstitute AAV DNA replication in vitro using purified herpes
      simplex virus type 1 (HSV-1) replication proteins. We show that the HSV-1 UL5,
      UL8, UL29, UL30, UL42, and UL52 gene products along with the AAV Rep68 protein
      are sufficient to initiate replication on duplex DNA containing the AAV origins
      of replication, resulting in products several hundred nucleotides in length.
      Initiation can occur also on templates containing only a Rep binding site and a
      terminal resolution site. We further demonstrate that initiation of DNA synthesis
      can take place with a subset of these factors: Rep68 and the UL29, UL30, and UL42
      gene products. Since the HSV polymerase and its accessory factor (the products of
      the UL30 and UL42 genes) are unable to efficiently perform synthesis by strand
      displacement, it is likely that in addition to creating a hairpin primer, the AAV
      Rep protein also acts as a helicase for DNA synthesis. The single-strand DNA
      binding protein (the UL29 gene product) presumably prevents reannealing of
      complementary strands. These results suggest that AAV can use the HSV replication
      apparatus to replicate its DNA. In addition, they may provide a first step for
      the development of a fully reconstituted AAV replication assay.

PMID- 11581394
TI  - A null mutation in the gene encoding the herpes simplex virus type 1 UL37
      polypeptide abrogates virus maturation.
AB  - The tegument is an integral and essential structural component of the herpes
      simplex virus type 1 (HSV-1) virion. The UL37 open reading frame of HSV-1 encodes
      a 120-kDa virion polypeptide which is a resident of the tegument. To analyze the
      function of the UL37-encoded polypeptide a null mutation was generated in the
      gene encoding this protein. In order to propagate this mutant virus, transformed
      cell lines that express the UL37 gene product in trans were produced. The null
      mutation was transferred into the virus genome using these complementing cell
      lines. A mutant virus designated KDeltaUL37 was isolated based on its ability to
      form plaques on the complementing cell line but not on nonpermissive
      (noncomplementing) Vero cells. This virus was unable to grow in Vero cells;
      therefore, UL37 encodes an essential function of the virus. The mutant virus
      KDeltaUL37 produced capsids containing DNA as judged by sedimentation analysis of
      extracts derived from infected Vero cells. Therefore, the UL37 gene product is
      not required for DNA cleavage or packaging. The UL37 mutant capsids were tagged
      with the smallest capsid protein, VP26, fused to green fluorescent protein. This
      fusion protein decorates the capsid shell and consequently the location of the
      capsid and the virus particle can be visualized in living cells. Late in
      infection, KDeltaUL37 capsids were observed to accumulate at the periphery of the
      nucleus as judged by the concentration of fluorescence around this organelle.
      Fluorescence was also observed in the cytoplasm in large puncta. Fluorescence at
      the plasma membrane, which indicated maturation and egress of virions, was
      observed in wild-type-infected cells but was absent in KDeltaUL37-infected cells.
      Ultrastructural analysis of thin sections of infected cells revealed clusters of
      DNA-containing capsids in the proximity of the inner nuclear membrane.
      Occasionally enveloped capsids were observed between the inner and outer nuclear
      membranes. Clusters of unenveloped capsids were also observed in the cytoplasm of
      KDeltaUL37-infected cells. Enveloped virions, which were observed in the
      cytoplasm of wild-type-infected cells, were never detected in the cytoplasm of
      KDeltaUL37-infected cells. Crude cell fractionation of infected cells using
      detergent lysis demonstrated that two-thirds of the UL37 mutant particles were
      associated with the nuclear fraction, unlike wild-type particles, which were
      predominantly in the cytoplasmic fraction. These data suggest that in the absence
      of UL37, the exit of capsids from the nucleus is slowed. UL37 mutant particles
      can participate in the initial envelopment at the nuclear membrane, although this
      process may be impaired in the absence of UL37. Furthermore, the naked capsids
      deposited in the cytoplasm are unable to progress further in the morphogenesis
      pathway, which suggests that UL37 is also required for egress and reenvelopment.
      Therefore, the UL37 gene product plays a key role in the early stages of the
      maturation pathway that give rise to an infectious virion.

PMID- 11581395
TI  - mRNA decay during herpesvirus infections: interaction between a putative viral
      nuclease and a cellular translation factor.
AB  - During lytic infections, the virion host shutoff (Vhs) protein (UL41) of herpes
      simplex virus destabilizes both host and viral mRNAs. By accelerating mRNA decay,
      it helps determine the levels and kinetics of viral and cellular gene expression.
      In vivo, Vhs shows a strong preference for mRNAs, as opposed to non-mRNAs, and
      degrades the 5' end of mRNAs prior to the 3' end. In contrast, partially purified
      Vhs is not restricted to mRNAs and causes cleavage of target RNAs at various
      sites throughout the molecule. To explain this discrepancy, we searched for
      cellular proteins that interact with Vhs using the Saccharomyces cerevisiae two
      hybrid system. Vhs was found to interact with the human translation initiation
      factor, eIF4H. This interaction was verified by glutathione S-transferase pull
      down experiments and by coimmunoprecipitation of Vhs and epitope-tagged eIF4H
      from extracts of mammalian cells. The interaction was abolished by several point
      mutations in Vhs that abrogate its ability to degrade mRNAs in vivo. The results
      suggest that Vhs is a viral mRNA degradation factor that is targeted to mRNAs,
      and to regions of translation initiation, through an interaction with eIF4H.

PMID- 11581396
TI  - Functional and antigenic characterization of human, rhesus macaque, pigtailed
      macaque, and murine DC-SIGN.
AB  - DC-SIGN, a type II membrane protein with a C-type lectin binding domain that is
      highly expressed on mucosal dendritic cells (DCs) and certain macrophages in
      vivo, binds to ICAM-3, ICAM-2, and human and simian immunodeficiency viruses (HIV
      and SIV). Virus captured by DC-SIGN can be presented to T cells, resulting in
      efficient virus infection, perhaps representing a mechanism by which virus can be
      ferried via normal DC trafficking from mucosal tissues to lymphoid organs in
      vivo. To develop reagents needed to characterize the expression and in vivo
      functions of DC-SIGN, we cloned, expressed, and analyzed rhesus macaque,
      pigtailed macaque, and murine DC-SIGN and made a panel of monoclonal antibodies
      (MAbs) to human DC-SIGN. Rhesus and pigtailed macaque DC-SIGN proteins were
      highly similar to human DC-SIGN and bound and transmitted HIV type 1 (HIV-1), HIV
      2, and SIV to receptor-positive cells. In contrast, while competent to bind
      virus, murine DC-SIGN did not transmit virus to receptor-positive cells under the
      conditions tested. Thus, mere binding of virus to a C-type lectin does not
      necessarily mean that transmission will occur. The murine and macaque DC-SIGN
      molecules all bound ICAM-3. We mapped the determinants recognized by a panel of
      16 MAbs to the repeat region, the lectin binding domain, and the extreme C
      terminus of DC-SIGN. One MAb was specific for DC-SIGN, failing to cross-react
      with DC-SIGNR. Most MAbs cross-reacted with rhesus and pigtailed macaque DC-SIGN,
      although none recognized murine DC-SIGN. Fifteen of the MAbs recognized DC-SIGN
      on DCs, with MAbs to the repeat region generally reacting most strongly. We
      conclude that rhesus and pigtailed macaque DC-SIGN proteins are structurally and
      functionally similar to human DC-SIGN and that the reagents that we have
      developed will make it possible to study the expression and function of this
      molecule in vivo.

PMID- 11581397
TI  - Potential transmission of human polyomaviruses through the gastrointestinal tract
      after exposure to virions or viral DNA.
AB  - The mechanism of human-to-human transmission of the polyomaviruses JC virus (JCV)
      and BK virus (BKV) has not been firmly established with regard to possible human
      exposure. JCV and BKV have been found in sewage samples from different
      geographical areas in Europe, Africa, and the United States, with average
      concentrations of 10(2) to 10(3) JCV particles/ml and 10(1) to 10(2) BKV
      particles/ml. Selected polyomavirus-positive sewage samples were further
      characterized. The JCV and BKV present in these samples were identified by
      sequencing of the intergenic region (the region found between the T antigen and
      VP coding regions) of JCV and the VP1 region of BKV. The regulatory region of the
      JCV and BKV strains found in sewage samples presented archetypal or archetype
      like genetic structures, as described for urine samples. The stability (the time
      required for a 90% reduction in the virus concentration) of the viral particles
      in sewage at 20 degrees C was estimated to be 26.7 days for JCV and 53.6 days for
      BKV. The presence of JCV in 50% of the shellfish samples analyzed confirmed the
      stability of these viral particles in the environment. BKV and JCV particles were
      also found to be stable at pH 5; however, treatment at a pH lower than 3 resulted
      in the detection of free viral DNA. Since most humans are infected with JCV and
      BKV, these data indicate that the ingestion of contaminated water or food could
      represent a possible portal of entrance of these viruses or polyomavirus DNA into
      the human population.

PMID- 11581398
TI  - Yaba-like disease virus: an alternative replicating poxvirus vector for cancer
      gene therapy.
AB  - Vaccinia virus is being investigated as a replicating vector for tumor-directed
      gene therapy. However, the majority of cancer patients have preformed immunologic
      reactivity against vaccinia virus, as a result of smallpox vaccination, which may
      limit its use as a vector. The Yaba-like disease (YLD) virus was investigated
      here as an alternative, replicating poxvirus for cancer gene therapy. We have
      demonstrated that the YLD virus does not cross-react with vaccinia virus
      antibodies, and it replicates efficiently in human tumor cells. YLD virus can be
      expanded and purified to high titer in CV-1 cells under conditions utilized for
      vaccinia virus. The YLD virus RNA polymerase was able to express genes regulated
      by a synthetic promoter designed for use in orthopoxviruses. We sequenced the YLD
      virus TK gene and created a shuttle plasmid, which allowed the recombination of
      the green fluorescent protein (GFP) gene into the YLD virus. In a murine model of
      ovarian cancer, up to 38% of cells in the tumor expressed the GFP transgene 12
      days after intraperitoneal virus delivery. YLD virus has favorable
      characteristics as a vector for cancer gene therapy, and this potential should be
      explored further.

PMID- 11581399
TI  - Herpes simplex virus with highly reduced gD levels can efficiently enter and
      spread between human keratinocytes.
AB  - The rapid spread of herpes simplex virus type 1 (HSV-1) in mucosal epithelia and
      neuronal tissue depends primarily on the ability of the virus to navigate within
      polarized cells and the tissues they constitute. To understand HSV entry and the
      spread of virus across cell junctions, we have previously characterized a human
      keratinocyte cell line, HaCaT. These cells appear to reflect cells infected in
      vivo more accurately than many of the cultured cells used to propagate HSV. HSV
      mutants lacking gE/gI are highly compromised in spread within epithelial and
      neuronal tissues and also show defects in cell-to-cell spread in HaCaT cells, but
      not in other, nonpolarized cells. HSV gD is normally considered absolutely
      essential for entry and cell-to-cell spread, both in cultured cells and in vivo.
      Here, an HSV-1 gD mutant virus, F-US6kan, was found to efficiently enter HaCaT
      cells and normal human keratinocytes and could spread from cell to cell without
      gD provided by complementing cells. By contrast, entry and spread into other
      cells, especially highly transformed cells commonly used to propagate HSV, were
      extremely inefficient. Further analyses of F-US6kan indicated that this mutant
      expressed extraordinarily low (1/500 wild-type) levels of gD. Neutralizing anti
      gD monoclonal antibodies inhibited entry of F-US6kan, suggesting F-US6kan
      utilized this small amount of gD to enter cells. HaCaT cells expressed high
      levels of an HSV gD receptor, HveC, and entry of F-US6kan into HaCaT cells could
      also be inhibited with antibodies specific for HveC. Interestingly, anti-HveC
      antibodies were not fully able to inhibit entry of wild-type HSV-1 into HaCaT
      cells. These results help to uncover important properties of HSV and human
      keratinocytes. HSV, with exceedingly low levels of a crucial receptor-binding
      glycoprotein, can enter cells expressing high levels of receptor. In this case,
      surplus gD may be useful to avoid neutralization by anti-gD antibodies.

PMID- 11581400
TI  - Interleukin-7 in plasma correlates with CD4 T-cell depletion and may be
      associated with emergence of syncytium-inducing variants in human
      immunodeficiency virus type 1-positive individuals.
AB  - Human immunodeficiency virus type 1 (HIV-1) primary infection is characterized by
      the use of CCR5 as a coreceptor for viral entry, which is associated with the non
      syncytium-inducing (NSI) phenotype in lymphoid cells. Syncytium-inducing (SI)
      variants of HIV-1 appear in advanced stages of HIV-1 infection and are
      characterized by the use of CXCR4 as a coreceptor. The emergence of SI variants
      is accompanied by a rapid decrease in the number of T cells. However, it is
      unclear why SI variants emerge and what factors trigger the evolution of HIV from
      R5 to X4 variants. Interleukin-7 (IL-7), a cytokine produced by stromal cells of
      the thymus and bone marrow and by keratin, is known to play a key role in T-cell
      development. We evaluated IL-7 levels in plasma of healthy donors and HIV
      positive patients and found significantly higher levels in HIV-positive patients.
      There was a negative correlation between circulating IL-7 levels and CD4(+) T
      cell count in HIV-positive patients (r = -0.621; P < 0.001), suggesting that IL-7
      may be involved in HIV-induced T-cell depletion and disease progression. IL-7
      levels were higher in individuals who harbored SI variants and who had progressed
      to having CD4 cell counts of lower than 200 cells/microl than in individuals with
      NSI variants at a similar stage of disease. IL-7 induced T-cell proliferation and
      up-regulated CXCR4 expression in peripheral blood mononuclear cells in vitro.
      Taken together, our results suggest a role for IL-7 in the maintenance of T-cell
      regeneration and depletion by HIV in infected individuals and a possible
      relationship between IL-7 levels and the emergence of SI variants.

PMID- 11581401
TI  - cdc2 cyclin-dependent kinase binds and phosphorylates herpes simplex virus 1
      U(L)42 DNA synthesis processivity factor.
AB  - Earlier studies have shown that cdc2 kinase is activated during herpes simplex
      virus 1 infection and that its activity is enhanced late in infection even though
      the levels of cyclin A and B are decreased below levels of detection.
      Furthermore, activation of cdc2 requires the presence of infected cell protein
      no. 22 and the U(L)13 protein kinase, the same gene products required for optimal
      expression of a subset of late genes exemplified by U(S)11, U(L)38, and U(L)41.
      The possibility that the activation of cdc2 and expression of this subset may be
      connected emerged from the observation that dominant negative cdc2 specifically
      blocked the expression of U(S)11 protein in cells infected and expressing
      dominant negative cdc2. Here we report that in the course of searching for a
      putative cognate partner for cdc2 that may have replaced cyclins A and B, we
      noted that the DNA polymerase processivity factor encoded by the U(L)42 gene
      contains a degenerate cyclin box and has been reported to be structurally related
      to proliferating cell nuclear antigen, which also binds cdk2. Consistent with
      this finding, we report that (i) U(L)42 is able to physically interact with cdc2
      at both the amino-terminal and carboxyl-terminal domains, (ii) the carboxyl
      terminal domain of U(L)42 can be phosphorylated by cdc2, (iii) immunoprecipitates
      obtained with anti U(L)42 antibody contained a roscovitine-sensitive kinase
      activity, (iv) kinase activity associated with U(L)42 could be immunodepleted by
      antibody to cdc2, and (v) U(L)42 transfected into cells associates with a
      nocodazole-enhanced kinase. We conclude that U(L)42 can associate with cdc2 and
      that the kinase activity has the characteristic traits of cdc2 kinase.

PMID- 11581402
TI  - Identification of acidic and aromatic residues in the Zta activation domain
      essential for Epstein-Barr virus reactivation.
AB  - Epstein-Barr virus (EBV) lytic cycle transcription and DNA replication require
      the transcriptional activation function of the viral immediate-early protein Zta.
      We describe a series of alanine substitution mutations in the Zta activation
      domain that reveal two functional motifs based on amino acid composition. Alanine
      substitution of single or paired hydrophobic aromatic amino acid residues
      resulted in modest transcription activation defects, while combining four
      substitutions of aromatic residues (F22/F26/W74/F75) led to more severe
      transcription defects. Substitution of acidic amino acid residue E27, D35, or E54
      caused severe transcription defects on most viral promoters. Promoter- and cell
      specific defects were observed for some substitution mutants. Aromatic residues
      were required for Zta interaction with TFIIA-TFIID and the CREB-binding protein
      (CBP) and for stimulation of CBP histone acetyltransferase activity in vitro. In
      contrast, acidic amino acid substitution mutants interacted with TFIIA-TFIID and
      CBP indistinguishably from the wild type. The nuclear domain 10 (ND10) protein
      SP100 was dispersed by most Zta mutants, but acidic residue mutations led to
      reduced, while aromatic substitution mutants led to increased SP100 nuclear
      staining. Acidic residue substitution mutants had more pronounced defects in
      transcription activation of endogenous viral genes in latently infected cells and
      for viral replication, as measured by the production of infectious virus. One
      mutant, K12/F13, was incapable of stimulating EBV lytic replication but had only
      modest transcription defects. These results indicate that Zta stimulates viral
      reactivation through two nonredundant structural motifs, one of which interacts
      with general transcription factors and coactivators, and the other has an
      essential but as yet not understood function in lytic transcription.

PMID- 11581403
TI  - Sustained activation of mitogen-activated protein kinases and activator protein 1
      by the hepatitis B virus X protein in mouse hepatocytes in vivo.
AB  - Transcriptional activation of diverse cellular genes by the X protein (HBx) of
      hepatitis B virus (HBV) has been suggested as one of the mechanisms for HBV
      associated hepatocellular carcinoma. However, such functions of HBx have been
      studied using transformed cells in culture and have not been examined in the
      normal adult hepatocytes, a natural host of HBV. Using an efficient hepatocyte
      specific virus-based gene delivery system developed in our laboratory earlier, we
      studied the HBx action in vivo. We demonstrate that following virosome-mediated
      delivery of HBx DNA, a large population (>50%) of hepatocytes express the HBx
      protein in a dose-dependent manner, which induces a significant increase in the
      activity of extracellular signal-regulated kinases (ERKs) in the livers of HBx
      transfected mice. Inhibition of HBx-induced ERK activation following intravenous
      administration of PD98059, a mitogen-activated protein kinase kinase kinase (MEK)
      inhibitor, confirmed the requirement for MEK in the activation of ERKs by HBx.
      Induction of ERK activity by HBx was sustained for up to 30 days. Interestingly,
      sustained activation of c-Jun N-terminal kinases (JNKs) for up to 30 days was
      also noted. Such constitutive ERK and JNK activation as a consequence of
      continued HBx expression also led to sustained stimulation of further downstream
      events, such as increased levels of c-Jun and c-Fos proteins along with the
      persistent induction of activator protein 1 binding activity. Taken together, our
      data suggest a critical role of these molecules in HBx-mediated cell
      transformation.

PMID- 11581404
TI  - Rec (formerly Corf) function requires interaction with a complex, folded RNA
      structure within its responsive element rather than binding to a discrete
      specific binding site.
AB  - It was recently reported that the human endogenous retrovirus HTDV/HERV-K encodes
      the regulatory protein Rec (formerly designated Corf), which is functionally
      equivalent to the nuclear export adapter proteins Rev of human immunodeficiency
      virus and Rex of human T-cell leukemia virus. We have demonstrated that the Rec
      protein interacts with a characteristic 429-nucleotide RNA element, the Rec
      responsive element (RcRE), present in the 3' long terminal repeat of HTDV/HERV-K
      transcripts. In analogy to the Rev and Rex proteins, which have distinct RNA
      binding sites in their responsive elements, we have proposed that Rec may also
      have a defined binding site in the RcRE. In this report, we demonstrate that not
      every HTDV/HERV-K copy present in the human genome contains an active RcRE, and
      we characterize mutations that abrogate Rec function. In addition, we demonstrate
      that Rec function requires binding to a complex, folded RNA structure rather than
      binding to a discrete specific binding site, in contrast to Rev and Rex and their
      homologous responsive elements. We define four stem-loop structures in the RcRE
      that are essential for Rec function. Finally, we demonstrate that both Rev and
      Rex can mediate nuclear export through the RcRE but that their binding sites are
      different from each other and from that of Rec.

PMID- 11581405
TI  - African swine fever virus infection of porcine aortic endothelial cells leads to
      inhibition of inflammatory responses, activation of the thrombotic state, and
      apoptosis.
AB  - African swine fever (ASF) is an asymptomatic infection of warthogs and bushpigs,
      which has become an emergent disease of domestic pigs, characterized by
      hemorrhage, lymphopenia, and disseminated intravascular coagulation. It is caused
      by a large icosohedral double-stranded DNA virus, African swine fever virus
      (ASFV), with infection of macrophages well characterized in vitro and in vivo.
      This study shows that virulent isolates of ASFV also infect primary cultures of
      porcine aortic endothelial cells and bushpig endothelial cells (BPECs) in vitro.
      Kinetics of early and late gene expression, viral factory formation, replication,
      and secretion were similar in endothelial cells and macrophages. However, ASFV
      infected endothelial cells died by apoptosis, detected morphologically by
      terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and nuclear
      condensation and biochemically by poly(ADP-ribose) polymerase (PARP) cleavage at
      4 h postinfection (hpi). Immediate-early proinflammatory responses were
      inhibited, characterized by a lack of E-selectin surface expression and
      interleukin 6 (IL-6) and IL-8 mRNA synthesis. Moreover, ASFV actively
      downregulated interferon-induced major histocompatibility complex class I surface
      expression, a strategy by which viruses evade the immune system. Significantly,
      Western blot analysis showed that the 65-kDa subunit of the transcription factor
      NF-kappaB, a central regulator of the early response to viral infection,
      decreased by 8 hpi and disappeared by 18 hpi. Both disappearance of NF-kappaB p65
      and cleavage of PARP were reversed by the caspase inhibitor z-VAD-fmk.
      Interestingly, surface expression and mRNA transcription of tissue factor, an
      important initiator of the coagulation cascade, increased 4 h after ASFV
      infection. These data suggest a central role for vascular endothelial cells in
      the hemorrhagic pathogenesis of the disease. Since BPECs infected with ASFV also
      undergo apoptosis, resistance of the natural host must involve complex
      pathological factors other than viral tropism.

PMID- 11581406
TI  - DDB2 induces nuclear accumulation of the hepatitis B virus X protein
      independently of binding to DDB1.
AB  - The hepatitis B virus (HBV) X protein (HBx) is critical for the life cycle of the
      virus. HBx associates with several host cell proteins including the DDB1 subunit
      of the damaged-DNA binding protein DDB. Recent studies on the X protein encoded
      by the woodchuck hepadnavirus have provided correlative evidence indicating that
      the interaction with DDB1 is important for establishment of infection by the
      virus. In addition, the interaction with DDB1 has been implicated in the nuclear
      localization of HBx. Because the DDB2 subunit of DDB is required for the nuclear
      accumulation of DDB1, we investigated the role of DDB2 in the nuclear
      accumulation of HBx. Here we show that expression of DDB2 increases the nuclear
      levels of HBx. Several C-terminal deletion mutants of DDB2 that fail to bind DDB1
      are able to associate with HBx, suggesting that DDB2 may associate with HBx
      independently of binding to DDB1. We also show that DDB2 enhances the nuclear
      accumulation of HBx independently of binding to DDB1, since a mutant that does
      not bind DDB1 is able to enhance the nuclear accumulation of HBx. HBV infection
      is associated with liver pathogenesis. We show that the nuclear levels of DDB1
      and DDB2 are tightly regulated in hepatocytes. Studies with regenerating mouse
      liver indicate that during late G1 phase the nuclear levels of both subunits of
      DDB are transiently increased, followed by a sharp decrease in S phase. Taken
      together, these results suggest that DDB1 and DDB2 would participate in the
      nuclear functions of HBx effectively only during the late-G1 phase of the cell
      cycle.

PMID- 11581407
TI  - Efficient c-kit receptor-targeted gene transfer to primary human CD34-selected
      hematopoietic stem cells.
AB  - We have previously reported effective gene transfer with a targeted molecular
      conjugate adenovirus vector through the c-kit receptor in hematopoietic
      progenitor cell lines. However, a c-kit-targeted recombinant retroviral vector
      failed to transduce cells, indicating the existence of significant differences
      for c-kit target gene transfer between these two viruses. Here we demonstrate
      that conjugation of an adenovirus to a c-kit-retargeted retrovirus vector enables
      retroviral transduction. This finding suggests the requirement of endosomalysis
      for successful c-kit-targeted gene transfer. Furthermore, we show efficient gene
      transfer to, and high transgene expression (66%) in, CD34-selected, c-kit(+)
      human peripheral blood stem cells using a c-kit-targeted adenovirus vector. These
      findings may have important implications for future vector development in c-kit
      targeted stem cell gene transfer.

PMID- 11581408
TI  - The transgenic ICP4 promoter is activated in Schwann cells in trigeminal ganglia
      of mice latently infected with herpes simplex virus type 1.
AB  - Herpes simplex virus type 1 (HSV-1) establishes a latent infection in neurons of
      sensory ganglia, including those of the trigeminal ganglia. Latent viral
      infection has been hypothesized to be regulated by restriction of viral immediate
      early gene expression in neurons. Numerous in situ hybridization studies in mice
      and in humans have shown that transcription from the HSV-1 genome in latently
      infected neurons is limited to the latency-associated transcripts. In other
      studies, immediate-early gene (ICP4) transcripts have been detected by reverse
      transcription-PCR (RT-PCR) in homogenates of latently infected trigeminal ganglia
      of mice. We used reporter transgenic mice containing the HSV-1(F) ICP4 promoter
      fused to the coding sequence of the beta-galactosidase gene to determine whether
      neurons in latently infected trigeminal ganglia activated the ICP4 promoter. Mice
      were inoculated via the corneal route with HSV-1(F). At 5, 11, 23, and 37 days
      postinfection (dpi), trigeminal ganglia were examined for beta-galactosidase
      positive cells. The numbers of beta-galactosidase-positive neurons and
      nonneuronal cells were similar at 5 dpi. The number of positive neurons decreased
      at 11 dpi and returned to the level of mock-inoculated transgenic controls at 23
      and 37 dpi. The number of positive nonneuronal cells increased at 11 and 23 dpi
      and remained elevated at 37 dpi. Viral proteins were detected in neurons and
      nonneuronal cells in acutely infected ganglia, but were not detected in latently
      infected ganglia. Colabeling experiments confirmed that the transgenic ICP4
      promoter was activated in Schwann cells during latent infection. These findings
      suggest that the cells that express the HSV-1 ICP4 gene in latently infected
      ganglia are not neurons.

PMID- 11581409
TI  - Poliovirus protein 3A inhibits tumor necrosis factor (TNF)-induced apoptosis by
      eliminating the TNF receptor from the cell surface.
AB  - Viral infections often trigger host defensive reactions by activating intrinsic
      (intracellular) and extrinsic (receptor-mediated) apoptotic pathways. Poliovirus
      is known to encode an antiapoptotic function(s) suppressing the intrinsic
      pathway. Here, the effect of poliovirus nonstructural proteins on cell
      sensitivity to tumor necrosis factor (TNF)-induced (i.e., receptor-mediated)
      apoptosis was studied. This sensitivity is dramatically enhanced by the viral
      proteinase 2A, due, most likely, to inhibition of cellular translation. On the
      other hand, cells expressing poliovirus noncapsid proteins 3A and 2B exhibit
      strong TNF resistance. Expression of 3A neutralizes the proapoptotic activity of
      2A and results in a specific suppression of TNF signaling, including the lack of
      activation of NF-kappaB, due to elimination of the TNF receptor from the cell
      surface. In agreement with this, poliovirus infection results in a dramatic
      decrease in TNF receptor abundance on the surfaces of infected cells as early as
      4 h postinfection. Poliovirus proteins that confer resistance to TNF interfere
      with endoplasmic reticulum-Golgi protein trafficking, and their effect on TNF
      signaling can be imitated by brefeldin A, suggesting that the mechanism of
      poliovirus-mediated resistance to TNF is a result of aberrant TNF receptor
      trafficking.

PMID- 11581410
TI  - CD4(+) T cells induced by a DNA vaccine: immunological consequences of epitope
      specific lysosomal targeting.
AB  - Our previous studies have shown that targeting DNA vaccine-encoded major
      histocompatibility complex class I epitopes to the proteasome enhanced CD8(+) T
      cell induction and protection against lymphocytic choriomeningitis virus (LCMV)
      challenge. Here, we expand these studies to evaluate CD4(+) T-cell responses
      induced by DNA immunization and describe a system for targeting proteins and
      minigenes to lysosomes. Full-length proteins can be targeted to the lysosomal
      compartment by covalent attachment to the 20-amino-acid C-terminal tail of
      lysosomal integral membrane protein-II (LIMP-II). Using minigenes encoding
      defined T-helper epitopes from lymphocytic choriomeningitis virus, we show that
      the CD4(+) T-cell response induced by the NP(309-328) epitope of LCMV was greatly
      enhanced by addition of the LIMP-II tail. However, the immunological consequence
      of lysosomal targeting is not invariably positive; the CD4(+) T-cell response
      induced by the GP(61-80) epitope was almost abolished when attached to the LIMP
      II tail. We identify the mechanism which underlies this marked difference in
      outcome. The GP(61-80) epitope is highly susceptible to cleavage by cathepsin D,
      an aspartic endopeptidase found almost exclusively in lysosomes. We show, using
      mass spectrometry, that the GP(61-80) peptide is cleaved between residues F(74)
      and K(75) and that this destroys its ability to stimulate virus-specific CD4(+) T
      cells. Thus, the immunological result of lysosomal targeting varies, depending
      upon the primary sequence of the encoded antigen. We analyze the effects of
      CD4(+) T-cell priming on the virus-specific antibody and CD8(+) T-cell responses
      which are mounted after virus infection and show that neither response appears to
      be accelerated or enhanced. Finally, we evaluate the protective benefits of
      CD4(+) T-cell vaccination in the LCMV model system; in contrast to DNA vaccine
      induced CD8(+) T cells, which can confer solid protection against LCMV challenge,
      DNA vaccine-mediated priming of CD4(+) T cells does not appear to enhance the
      vaccinee's ability to combat viral challenge.

PMID- 11581411
TI  - Identification of genes involved in the host response to neurovirulent alphavirus
      infection.
AB  - Single-amino-acid mutations in Sindbis virus proteins can convert clinically
      silent encephalitis into uniformly lethal disease. However, little is known about
      the host gene response during avirulent and virulent central nervous system (CNS)
      infections. To identify candidate host genes that modulate alphavirus
      neurovirulence, we utilized GeneChip Expression analysis to compare CNS gene
      expression in mice infected with two strains of Sindbis virus that differ by one
      amino acid in the E2 envelope glycoprotein. Infection with Sindbis virus, dsTE12H
      (E2-55 HIS), resulted in 100% mortality in 10-day-old mice, whereas no disease
      was observed in mice infected with dsTE12Q (E2-55 GLN). dsTE12H, compared with
      dsTE12Q, replicated to higher titers in mouse brain and induced more CNS
      apoptosis. Infection with the neurovirulent dsTE12H strain was associated with
      both a greater number of host genes with increased expression and greater changes
      in levels of host gene expression than was infection with the nonvirulent dsTE12Q
      strain. In particular, dsTE12H infection resulted in greater increases in the
      levels of mRNAs encoding chemokines, proteins involved in antigen presentation
      and protein degradation, complement proteins, interferon-regulated proteins, and
      mitochondrial proteins. At least some of these increases may be beneficial for
      the host, as evidenced by the demonstration that enforced expression of the
      antiapoptotic mitochondrial protein peripheral benzodiazepine receptor (PBR)
      protects neonatal mice against lethal Sindbis virus infection. Thus, our findings
      identify specific host genes that may play a role in the host protective or
      pathologic response to neurovirulent Sindbis virus infection.

PMID- 11581412
TI  - Role for the adenovirus IVa2 protein in packaging of viral DNA.
AB  - Although it has been demonstrated that the adenovirus IVa2 protein binds to the
      packaging domains on the viral chromosome and interacts with the viral L1 52/55
      kDa protein, which is required for viral DNA packaging, there has been no direct
      evidence demonstrating that the IVa2 protein is involved in DNA packaging. To
      understand in greater detail the DNA packaging mechanisms of adenovirus, we have
      asked whether DNA packaging is serotype or subgroup specific. We found that Ad7
      (subgroup B), Ad12 (subgroup A), and Ad17 (subgroup D) cannot complement the
      defect of an Ad5 (subgroup C) mutant, pm8001, which does not package its DNA due
      to a mutation in the L1 52/55-kDa gene. This indicates that the DNA packaging
      systems of different serotypes cannot interact productively with Ad5 DNA. Based
      on this, a chimeric virus containing the Ad7 genome except for the inverted
      terminal repeats and packaging sequence from Ad5 was constructed. This chimeric
      virus replicates its DNA and synthesizes Ad7 proteins, but it cannot package its
      DNA in 293 cells or 293 cells expressing the Ad5 L1 52/55-kDa protein. However,
      this chimeric virus packages its DNA in 293 cells expressing the Ad5 IVa2
      protein. These results indicate that the IVa2 protein plays a role in viral DNA
      packaging and that its function is serotype specific. Since this chimeric virus
      cannot package its own DNA, but produces all the components for packaging Ad7
      DNA, it may be a more suitable helper virus for the growth of Ad7 gutted vectors
      for gene transfer.

PMID- 11581413
TI  - Cytopathic effects of non-syncytium-inducing and syncytium-inducing human
      immunodeficiency virus type 1 variants on different CD4(+)-T-cell subsets are
      determined only by coreceptor expression.
AB  - In peripheral blood mononuclear cells, syncytium-inducing (SI) human
      immunodeficiency virus type 1 (HIV-1) infected and depleted all CD4(+) T cells,
      including naive T cells. Non-SI HIV-1 infected and depleted only the CCR5
      expressing T-cell subset. This may explain the accelerated CD4 cell loss after SI
      conversion in vivo.

PMID- 11581414
TI  - CD8(+) T lymphocytes mediate Borna disease virus-induced immunopathology
      independently of perforin.
AB  - Perforin-mediated lysis of target cells is the major antiviral effector mechanism
      of CD8(+) T lymphocytes. We have analyzed the role of perforin in a mouse model
      for CD8(+) T-cell-mediated central nervous system (CNS) immunopathology induced
      by Borna disease virus. When a defective perforin gene was introduced into the
      genetic background of the Borna disease-susceptible mouse strain MRL, the
      resulting perforin-deficient mice developed strong neurological disease in
      response to infection indistinguishable from that of their perforin-expressing
      littermates. The onset of disease was slightly delayed. Brains of diseased
      perforin-deficient mice showed similar amounts and a similar distribution of
      CD8(+) T cells as wild-type animals. Perforin deficiency had no impact on the
      kinetics of viral spread through the CNS. Unlike brain lymphocytes from diseased
      wild-type mice, lymphocytes from perforin-deficient MRL mice showed no in vitro
      cytolytic activity towards target cells expressing the nucleoprotein of Borna
      disease virus. Taken together, these results demonstrate that CD8(+) T cells
      mediate Borna disease independent of perforin. They further suggest that the
      pathogenic potential of CNS-infiltrating CD8(+) T cells does not primarily reside
      in their lytic activity but rather in other functions.

PMID- 11581415
TI  - Role of tachykinins in the host response to murine gammaherpesvirus infection.
AB  - Tachykinins function not only as neurotransmitters but also as immunological
      mediators. We used infection of tachykinin-deficient (PPT-A(-/-)) mice and wild
      type controls with murine gammaherpesvirus to assess the role of tachykinins in
      the host response to a virus infection. Although infection was ultimately
      controlled in PPT-A(-/-) mice, there were higher titers of infectious virus in
      the lungs, accompanied by a more rapid influx of inflammatory cells. Clearance of
      latently infected cells from the spleen was also delayed. This is the first
      report of the direct influence of tachykinins in the host response to a virus
      infection.

PMID- 11581416
TI  - The synthetic peptide P-197 inhibits human T-cell leukemia virus type 1 envelope
      mediated syncytium formation by a mechanism that is independent of Hsc70.
AB  - Entry of human T-cell leukemia virus type 1 (HTLV-1) into cells is mediated by
      the viral envelope glycoproteins gp46 and gp21. The gp46 surface glycoprotein
      binds to a poorly characterized cell surface receptor, thereby promoting the gp21
      dependent fusion of the viral and cellular membranes. Interestingly, a synthetic
      peptide (P-197) simulating amino acids 197 to 216 of gp46 strongly inhibits
      envelope-dependent membrane fusion with Molt-4 target cells. It has been
      suggested that this peptide acts by competitively binding to Hsc70, a putative
      cellular receptor for HTLV-1. We now demonstrate that P-197 inhibits membrane
      fusion among diverse HTLV-1-permissive target cells. Importantly, most of these
      cells lack detectable levels of Hsc70, indicating that P-197 inhibits membrane
      fusion by a mechanism that is Hsc70 independent. We now suggest that competition
      for primary receptor binding is unlikely to account for the inhibitory activity
      of P-197. Understanding the mechanism by which P-197 functions may reveal
      concepts of general relevance to antiretroviral chemotherapy.

PMID- 11581417
TI  - Human immunodeficiency virus type 1 env sequences from Calcutta in eastern India:
      identification of features that distinguish subtype C sequences in India from
      other subtype C sequences.
AB  - India is experiencing a rapid spread of human immunodeficiency virus type 1 (HIV
      1), primarily through heterosexual transmission of subtype C viruses. To
      delineate the molecular features of HIV-1 circulating in India, we sequenced the
      V3-V4 region of viral env from 21 individuals attending an HIV clinic in
      Calcutta, the most populous city in the eastern part of the country, and analyzed
      these and the other Indian sequences in the HIV database. Twenty individuals were
      infected with viruses having a subtype C env, and one had viruses with a subtype
      A env. Analyses of 192 subtype C sequences that included one sequence for each
      subject from this study and from the HIV database revealed that almost all
      sequences from India, along with a small number from other countries, form a
      phylogenetically distinct lineage within subtype C, which we designate C(IN).
      Overall, C(IN) lineage sequences were more closely related to each other (level
      of diversity, 10.2%) than to subtype C sequences from Botswana, Burundi, South
      Africa, Tanzania, and Zimbabwe (range, 15.3 to 20.7%). Of the three positions
      identified as signature amino acid substitution sites for C(IN) sequences (K340E,
      K350A, and G429E), 56% of the C(IN) sequences contained all three amino acids
      while 87% of the sequences contained at least two of these substitutions. Among
      the non-C(IN) sequences, all three amino acids were present in 2%, while 22%
      contained two or more of these amino acids. These results suggest that much of
      the current Indian epidemic is descended from a single introduction into the
      country. Identification of conserved signature amino acid positions could assist
      epidemiologic tracking and has implications for the development of a vaccine
      against subtype C HIV-1 in India.

PMID- 11581418
TI  - Epstein-Barr virus and the somatic hypermutation of immunoglobulin genes in
      Burkitt's lymphoma cells.
AB  - It has been suggested that Epstein-Barr virus (EBV) might suppress antibody
      maturation either by facilitating bypass of the germinal center reaction or by
      inhibiting hypermutation directly. However, by infecting the Burkitt's lymphoma
      (BL) cell line Ramos, which hypermutates constitutively and can be considered a
      transformed analogue of a germinal center B cell, with EBV as well as by
      transfecting it with selected EBV latency genes, we demonstrate that expression
      of EBV gene products does not lead to an inhibition of hypermutation. Moreover,
      we have identified two natural EBV-positive BL cell lines (ELI-BL and BL16) that
      hypermutate constitutively. Thus, contrary to expectations, EBV gene products do
      not appear to affect somatic hypermutation.

PMID- 11581419
TI  - Positively charged termini of the L2 minor capsid protein are necessary for
      papillomavirus infection.
AB  - Coexpression of bovine papillomavirus L1 with L2 mutants lacking either eight N
      terminal or nine C-terminal amino acids that encode positively charged domains
      resulted in wild-type levels of viral genome encapsidation. Despite wild-type
      binding to the cell surface, the resulting virions were noninfectious. An L2
      mutant encoding a scrambled version of the nine C-terminal residues restored
      infectivity, in contrast to an L2 mutant encoding a scrambled version of the N
      terminal residues.

PMID- 11581420
TI  - A chimeric human-bovine parainfluenza virus type 3 expressing measles virus
      hemagglutinin is attenuated for replication but is still immunogenic in rhesus
      monkeys.
AB  - The chimeric recombinant virus rHPIV3-N(B), a version of human parainfluenza
      virus type 3 (HPIV3) that is attenuated due to the presence of the bovine PIV3
      nucleocapsid (N) protein open reading frame (ORF) in place of the HPIV3 ORF, was
      modified to encode the measles virus hemagglutinin (HA) inserted as an
      additional, supernumerary gene between the HPIV3 P and M genes. This recombinant,
      designated rHPIV3-N(B)HA, replicated like its attenuated rHPIV3-N(B) parent virus
      in vitro and in the upper and lower respiratory tracts of rhesus monkeys,
      indicating that the insertion of the measles virus HA did not further attenuate
      rHPIV3-N(B) in vitro or in vivo. Monkeys immunized with rHPIV3-N(B)HA developed a
      vigorous immune response to both measles virus and HPIV3, with serum antibody
      titers to both measles virus (neutralizing antibody) and HPIV3 (hemagglutination
      inhibiting antibody) of over 1:500. An attenuated HPIV3 expressing a major
      protective antigen of measles virus provides a method for immunization against
      measles by the intranasal route, a route that has been shown with HPIV3 and
      respiratory syncytial virus vaccines to be relatively refractory to the
      neutralizing and immunosuppressive effects of maternally derived virus-specific
      serum antibodies. It should now be possible to induce a protective immune
      response against measles virus in 6-month-old infants, an age group that in
      developing areas of the world is not responsive to the current measles virus
      vaccine.

PMID- 11581421
TI  - Isomerization of a uniquely designed amplicon during herpes simplex virus
      mediated replication.
AB  - Herpes simplex virus (HSV) type 1 DNA isomerization was studied using a uniquely
      designed amplicon that mimics the viral genomic structure. The results revealed
      that amplicon concatemers frequently contain adjacent amplicon units with their
      segments in opposed orientations. These unusual concatemers were generated
      through homologous recombination, which does not require HSV DNA as the source of
      homology.

PMID- 11581422
TI  - Productive infection of primary macrophages with human herpesvirus 7.
AB  - Here we demonstrate replication of human herpesvirus 7 (HHV-7), a T-lymphotropic
      virus, in macrophages. Productive replication was lost after 2 weeks, but HHV-7
      DNA was detected up to 1 month after infection. Thus, macrophages become infected
      by HHV-7 and might play an important role as a viral reservoir, as has been
      demonstrated for human immunodeficiency virus type 1.

PMID- 11581423
TI  - Emergence and kinetics of simian immunodeficiency virus-specific CD8(+) T cells
      in the intestines of macaques during primary infection.
AB  - In this report, three Mamu-A*01(+) rhesus macaques were examined to compare the
      emergence of simian immunodeficiency virus (SIV)-specific CD8(+) T cells in the
      intestines and blood in early SIV infection using a major histocompatibility
      complex class I tetramer complexed with the Gag(181-189) peptide. Fourteen days
      after intravenous inoculation with SIVmac251, large numbers of SIV Gag(181-189)
      specific CD8(+) T cells were detected in the intestinal mucosa (3.1 to 11.5% of
      CD3(+) CD8(+) lymphocytes) as well as in the blood (3.1 to 13.4%) of all three
      macaques. By 21 days postinoculation, levels of tetramer-binding cells had
      dropped in both the intestines and blood. At day 63, however, levels of SIV
      Gag(181-189)-specific CD8(+) T cells in the intestines had rebounded in all three
      macaques to levels that were higher (8.6 to 18.7%) than those at day 21. In
      contrast, percentages of tetramer-binding cells in the peripheral blood remained
      comparatively stable (2.5 to 4.5%) at this time point. In summary, SIV Gag(181
      189)-specific CD8(+) T cells appeared in both the intestinal mucosa and
      peripheral blood at a comparable rate and magnitude in primary SIV infection.
      Given that the intestine is a major site of early viral replication as well as
      the site where most of the total body lymphocyte pool resides, these data
      indicate that it is also an early and important site of development of antiviral
      immune responses.

PMID- 11581424
TI  - Human immunodeficiency virus type 1 (HIV-1) non-B subtypes are similar to HIV-1
      subtype B in that coreceptor specificity is a determinant of cytopathicity in
      human lymphoid tissue infected ex vivo.
AB  - We sought to determine the relationship between virus-mediated CD4(+) T
      lymphocyte cytopathicity and viral coreceptor preference among various human
      immunodeficiency virus type 1 (HIV-1) subtypes in an ex vivo-infected human
      lymphoid tissue model. Our data show that all R5 HIV-1 infections resulted in
      mild depletion of CD4(+) T lymphocytes, whereas all X4 HIV-1 infections caused
      severe depletion of CD4(+) T lymphocytes regardless of their subtype origin.
      Thus, at least for the viruses within subtypes A, B, C, and E that were tested,
      coreceptor specificity is a critical factor that determines the ability of HIV-1
      to deplete CD4(+) T cells in human lymphoid tissue infected ex vivo.

PMID- 11581425
TI  - DC-SIGN interactions with human immunodeficiency virus: virus binding and
      transfer are dissociable functions.
AB  - The C-type lectins DC-SIGN and DC-SIGNR capture and transfer human
      immunodeficiency virus (HIV) to susceptible cells, although the underlying
      mechanism is unclear. Here we show that DC-SIGN/DC-SIGNR-mediated HIV
      transmission involves dissociable binding and transfer steps, indicating that
      efficient virus transmission is not simply due to tethering of virus to the cell
      surface.

PMID- 11581426
TI  - Cyclophilin A-independent replication of a human immunodeficiency virus type 1
      isolate carrying a small portion of the simian immunodeficiency virus SIV(MAC)
      gag capsid region.
AB  - Hybrid viruses between human immunodeficiency virus type 1 (HIV-1) and simian
      immunodeficiency virus strain mac (SIV(MAC)) are invaluable to various fields of
      HIV-1 research. To date, however, no replication-competent HIV-1 strain
      containing the gag capsid (CA) region of SIV(MAC) has been reported. To obtain
      the viable gag gene chimeric virus in an HIV-1 background, seven HIV-1 strains
      carrying a part of SIV(MAC) CA or a small deletion in the CA region were
      constructed and examined for their biological and biochemical characteristics.
      While all the recombinants and mutants were found to express Gag and to produce
      progeny virions on transfection, only one chimeric virus, which has 18 bp of SIV
      gag CA sequence in place of the region encoding the HIV-1 CA cyclophilin A (CyPA)
      binding loop, was infectious for human cell lines. Although this chimeric virus
      was unable to grow in monkey lymphocytic cells like wild-type (wt) HIV-1 did, it
      grew much better than wt virus in the presence of cyclosporin A in a human cell
      line which supports HIV-1 replication in a CyPA-dependent manner. These results
      indicate that the transfer of a small portion of the SIV(MAC) CA region to HIV-1
      could confer the CyPA-independent replication potential of SIV(MAC) on the virus.

PMID- 11581427
TI  - Efficient class I major histocompatibility complex down-regulation by simian
      immunodeficiency virus Nef is associated with a strong selective advantage in
      infected rhesus macaques.
AB  - Substitution of Y223F disrupts the ability of simian immunodeficiency virus (SIV)
      Nef to down-modulate major histocompatibility complex (MHC) class I from the cell
      surface but has no effect on other Nef functions, such as down-regulation of CD4,
      CD28, and CD3 cell surface expression or stimulation of viral replication and
      enhancement of virion infectivity. Inoculation of three rhesus macaques with the
      SIVmac239 Y223F-Nef variant revealed that this point mutation consistently
      reverts and that Nef activity in MHC class I down-modulation is fully restored
      within 4 weeks after infection. Our results demonstrate a strong selective
      pressure for a tyrosine at amino acid position 223 in SIV Nef, and they
      constitute evidence that Nef-mediated MHC class I down-regulation provides a
      selective advantage for viral replication in vivo.

PMID- 11581428
TI  - Biochemical analyses of the interactions between human immunodeficiency virus
      type 1 Vpr and p6(Gag).
AB  - The nonstructural human immunodeficiency virus type 1 Vpr protein is packaged
      into progeny virions at significant levels (approximately 200 copies/virion).
      Genetic analyses have demonstrated that efficient Vpr packaging is dependent upon
      a leucine-X-X-leucine-phenylalanine (LXXLF) motif located in the p6(Gag) domain
      of the structural Gag polyprotein. Recombinant proteins spanning full-length Vpr
      (Vpr(1-97)) or the amino-terminal 71 amino acids (Vpr(1-71)) formed specific
      complexes with recombinant p6 proteins in vitro. Complex formation required an
      intact LXXLF motif and exhibited an intrinsic dissociation constant of
      approximately 75 microM. Gel filtration and cross-linking analyses further
      revealed that Vpr(1-71) self-associated in solution. Our experiments demonstrate
      that Vpr can bind directly and specifically to p6 and suggest that
      oligomerization of both Vpr and Gag may serve to increase the avidity and
      longevity of Vpr-Gag complexes, thereby ensuring efficient Vpr packaging.

PMID- 11581429
TI  - Role of stem B, loop B, and nucleotides next to the primer binding site and the
      kissing-loop domain in human immunodeficiency virus type 1 replication and
      genomic-RNA dimerization.
AB  - Stem-loop B is a 12-nucleotide [nt]-long completely conserved sequence postulated
      to form a 4-bp stem and a 4-nt internal loop under the kissing-loop hairpin (klh)
      (nt 248 to 270) of human immunodeficiency virus type 1 (HIV-1) genomic RNA. We
      investigated its role in viral replication, genomic RNA dimerization, and
      dimerization of partial HIV-1 RNA transcripts. The putative CUCG246-CGAG277
      duplex was replaced by nine alternative complementary sequences, five likely to
      base pair only in short RNAs and four likely to base pair in long (approximately
      500-nt) RNAs, as assessed by the algorithm mfold. Among the five former
      sequences, none preserved genome dimerization and all reduced viral replication
      by 98 to 99.9%. Among the four latter sequences, three (MB6, -9, and -10)
      preserved genome dimerization, one (MB7) did not significantly inhibit it, and
      two (MB9 and -10) preserved viral replication. We conclude that duplex formation
      by stem B nucleotides is necessary for viral infectivity and complete genome
      dimerization. Deleting the 5' or 3' side of loop B or of stem B had little impact
      on dimerization of partial RNA transcript and no impact on klh folding (and, for
      loop B mutations, on stem B folding), but each deletion inhibited genome
      dimerization almost as much as klh destruction. This suggests that loop B is
      required for complete genome dimerization and that loop B and stem B stimulate
      dimerization only in very long RNAs and/or in the presence of unidentified viral
      and cellular factors. Finally, we asked if nine deletions or nucleotide
      substitutions within nt 200 to 242 and/or nt 282 to 335 could influence genome
      dimerization. These mutations had intermediate inhibitory impacts consistent with
      their predicted influence on stem B, loop B, and klh formation. Two exceptions
      were Delta200-226 and Delta236-242 genomic RNAs, which dimerized relatively
      poorly despite having neutral or positive influences on stem B, loop B, and klh
      folding.

PMID- 11581430
TI  - Sequence conservation and antigenic variation of the structural proteins of
      equine rhinitis A virus.
AB  - The nucleotide and deduced amino acid sequences of the P1 region of the genomes
      of 10 independent equine rhinitis A virus (ERAV) isolates were determined and
      found to be very closely related. A panel of seven monoclonal antibodies to the
      prototype virus ERAV.393/76 that bound to nonneutralization epitopes conserved
      among all 10 isolates was raised. In serum neutralization assays, rabbit
      polyclonal sera and sera from naturally and experimentally infected horses
      reacted in a consistent and discriminating manner with the 10 isolates, which
      indicated the existence of variation in the neutralization epitopes of these
      viruses.

PMID- 11581432
TI  - What if pediatric residents could bill for their outpatient services?
AB  - OBJECTIVE: We prospectively studied the potential of billing and coding practices
      of pediatric residents in outpatient clinics and extrapolated our results to
      assess the financial implications of billing inaccuracies. Using Medicare as a
      common measure of "currency," we also used the relative value unit (RVU) and
      ambulatory payment class methodologies as means of assessing the productivity and
      financial value of resident-staffed pediatric clinics. METHODS: Residents were
      asked to submit voluntarily shadow billing forms and documentation of outpatient
      clinic visits. Documentation of work was assessed by a blinded reviewer, and
      current procedure terminology evaluation and management codes were assigned.
      Comparisons between resident codes and calculated codes were made. Financial
      implications of physician productivity were calculated in terms of dollar amounts
      and RVUs. Resource intensity was measured using the ambulatory payment class
      methodology. RESULTS: A total of 344 charts were reviewed. Coding agreement for
      health maintenance visits was 86%, whereas agreement for acute care visits was
      38%. Eighty-three percent of coding disagreement in the latter group was
      resulting from undercoding by residents. Errors accounted for a 4.79% difference
      in potential reimbursement for all visit types and a 19.10% difference for acute
      care visits. No significant differences in shadow billing discrepancies were
      found between different levels of training. Residents were predicted to generate
      $67 230, $87 593, and $96 072 in Medicare revenue in the outpatient clinic
      setting during each successive year of training. On average, residents generated
      1.17 +/- 0.01 and 0.81 +/- 0.02 work RVUs for each health maintenance visit and
      office visit, respectively. Annual productivity from outpatient clinic settings
      was estimated at 548, 735, and 893 work RVUs in the postgraduate levels 1, 2, and
      3, respectively. CONCLUSION: When pediatric residents are not trained adequately
      in proper coding practices, the potential for billing discrepancies is high and
      potential reimbursement differences may be substantial. Discussion of financial
      issues should be considered in curriculum development.

PMID- 11581431
TI  - Human cytomegalovirus protein US2 interferes with the expression of human HFE, a
      nonclassical class I major histocompatibility complex molecule that regulates
      iron homeostasis.
AB  - HFE is a nonclassical class I major histocompatibility complex (MHC) molecule
      that is mutated in the autosomal recessive iron overload disease hereditary
      hemochromatosis. There is evidence linking HFE with reduced iron uptake by the
      transferrin receptor (TfR). Using a panel of HFE and TfR monoclonal antibodies to
      examine human HFE (hHFE)-expressing cell lines, we demonstrate the expression of
      stable and fully glycosylated TfR-free and TfR-associated hHFE/beta2m complexes.
      We show that both the stability and assembly of hHFE complexes can be modified by
      the human cytomegalovirus (HCMV) viral protein US2, known to interfere with the
      expression of classical class I MHC molecules. HCMV US2, but not US11, targets
      HFE molecules for degradation by the proteasome. Whether this interference with
      the regulation of iron metabolism by a viral protein is a means of potentiating
      viral replication remains to be determined. The reduced expression of classical
      class I MHC and HFE complexes provides the virus with an efficient tool for
      altering cellular metabolism and escaping certain immune responses.

PMID- 11581433
TI  - Management of febrile children in the age of the conjugate pneumococcal vaccine:
      a cost-effectiveness analysis.
AB  - OBJECTIVES: The optimal practice management of highly febrile 3- to 36-month-old
      children without a focal source has been controversial. The recent release of a
      conjugate pneumococcal vaccine may reduce the rate of occult bacteremia and alter
      the utility of empiric testing and treatment. The objective of this study was to
      determine the cost-effectiveness of 6 different management strategies of febrile
      3- to 36-month-old children at current and declining rates of occult pneumococcal
      bacteremia. METHODS: A cost-effectiveness (CE) analysis was performed to compare
      the strategies of "no work-up," "clinical judgment," "blood culture," "blood
      culture + treatment," "complete blood count (CBC) + selective blood culture and
      treatment," and "CBC and blood culture + selective treatment." A hypothetical
      cohort of 100 000 children who were 3 to 36 months of age and had a fever of
      >/=39 degrees C and no source of infection was modeled for each strategy. Our
      main outcome measures were cases of meningitis prevented, life-years saved
      compared with "no work-up," total cost (1999 dollars), and incremental CE ratios.
      RESULTS: When compared with "no work-up," the strategy of "CBC + selective blood
      culture and treatment" using a white blood cell (WBC) cutoff of 15 x 10(9)/L
      prevents 48 cases of meningitis, saves 86 life-years per 100 000 patients, and is
      less costly at the current rate of bacteremia (1.5%). Using the strategy of "CBC
      + selective blood culture and treatment" with a lower WBC cutoff of 10 x 10(9)/L
      costs an additional $72 300 per life-year saved. If the rate of bacteremia
      declines to 0.5%, then the incremental CE ratio of "clinical judgment" compared
      with "no work-up" is $38 000 per life-year saved; however, strategies that
      include empiric testing or treatment result in CE ratios greater than $300 000
      per life-year saved. CONCLUSIONS: "CBC + selective blood culture and treatment"
      using a WBC cutoff of 15 x 10(9)/L is cost-effective at the current rate of
      pneumococcal bacteremia. If the rate of occult bacteremia falls below 0.5% with
      widespread use of the conjugate pneumococcal vaccine, then strategies that use
      empiric testing and treatment should be eliminated.

PMID- 11581434
TI  - Improving parent knowledge about antibiotics: a video intervention.
AB  - OBJECTIVE: To determine whether an educational video could improve parent
      knowledge, beliefs, and behaviors about the appropriate use of oral antibiotics.
      STUDY DESIGN: A randomized, controlled trial was conducted in an urban primary
      care clinic and a suburban pediatric practice. Parents were randomly assigned to
      the intervention or control groups. Parents in the intervention group were asked
      to view a 20-minute video, specifically developed for this project, over a 2
      month period, and given a brochure about antibiotics. Parent knowledge, beliefs,
      and behaviors were assessed at the time of enrollment and then by telephone 2
      months later. RESULTS: A total of 193 (94%) of 206 parents completed the study.
      The groups were equivalent with respect to all important baseline
      characteristics. No differences were found for adjusted posttest means between
      the intervention and control groups for knowledge, beliefs, or behavior. For
      example, the intervention group scored 8.04 on the knowledge questionnaire (11
      true-false questions), compared with 7.82 for the control group. Subgroup
      analysis, based on site of enrollment, indicated that families in the
      intervention group from the primary care urban clinic improved their knowledge
      score (6.03 to 6.92) and were more likely to report that there were problems with
      children receiving too many antibiotics (intervention 67% vs control 34%).
      CONCLUSION: Overall, this video had only a modest effect on parent knowledge,
      beliefs, and self-reported behaviors regarding oral antibiotics. We believe that
      any campaign promoting the judicious use of oral antibiotics must use a
      multifaceted approach and target both parents and physicians.

PMID- 11581435
TI  - Effect of practice variation on resource utilization in infants hospitalized for
      viral lower respiratory illness.
AB  - OBJECTIVE: Hospital care for children with viral lower respiratory illness (VLRI)
      is highly variable, and its relationship to severity and impact on outcome is
      unclear. Using the Pediatric Comprehensive Severity Index, we analyzed the
      correlation of institutional practice variation with severity and resource
      utilization in 10 children's medical centers. METHODS: Demographics, clinical
      information, laboratory results, interventions, and outcomes were extracted from
      the charts of consecutive infants with VLRI from 10 children's medical centers.
      Pediatric Component of the Comprehensive Severity Index scoring was performed at
      admission and at maximum during hospitalization. The correlation of patient
      variables, interventions, and resource utilization at the patient level was
      compared with their correlation at the aggregate institutional level. RESULTS: Of
      601 patients, 1 died, 6 were discharged to home health care, 4 were discharged to
      rehabilitative care, and 2 were discharged to chronic nursing care. Individual
      patient admission severity score correlated positively with patient hospital
      costs (r = 0.48), but institutional average patient severity was negatively
      correlated with average institutional costs (r = -0.26). Maximal severity score
      correlated well with costs (r = 0.66) and length of stay (LOS; r = 0.64) at the
      patient level but poorly at the institutional level (r = 0.07 costs; r = 0.40
      LOS). The institutional intensity of therapy was negatively correlated with
      admission severity (r = -0.03) but strongly correlated with costs (r = 0.84) and
      LOS (r = 0.83). CONCLUSIONS: Institutional differences in care practices for
      children with VLRI were not explained by differences in patient severity and did
      not affect the children's recovery but correlated significantly with hospital
      costs and LOS.

PMID- 11581436
TI  - High rates of multiple antibiotic resistance in Streptococcus pneumoniae from
      healthy children living in isolated rural communities: association with
      cephalosporin use and intrafamilial transmission.
AB  - OBJECTIVE: Streptococcus pneumoniae is one of the most clinically significant
      pathogens with emerging antibiotic resistance. We performed a surveillance study
      in isolated rural populations of healthy children to estimate the prevalence of
      pneumococcal resistance and to contrast factors that predict pneumococcal
      carriage with those that specifically predict resistant pneumococcal carriage.
      METHODS: The study was conducted in 1998 in 2 rural communities in Utah. Families
      were recruited directly for participation through community canvassing.
      Surveillance nasopharyngeal cultures were obtained from children who were younger
      than 8 years. Antibiotic usage and information on other potential risk factors
      were obtained from questionnaires and local pharmacy records. Resistance was
      determined by testing isolates for susceptibility to penicillin, cefaclor,
      trimethoprim-sulfamethoxazole, erythromycin, ceftriaxone, and trovafloxacin.
      Selected resistant isolates were characterized further by serotyping, pulsed
      field gel electrophoresis, and Southern blot with DNA probes specific for the
      pneumococcal lytA gene and for antibiotic resistance genes. RESULTS: In April
      1998, surveillance nasopharyngeal cultures were obtained from 368 children aged
      </=8 years in community A and 369 children in community B. The number of
      antibiotic courses per child within 1 year before culture was higher in community
      B than A (mean: 2.2 vs 1.7). Conversely, oral cephalosporins were more frequently
      used in community A than B (community A: 22% received cephalosporins within 4
      months; community B: 12%). Colonization with S pneumoniae was detected in 24% of
      children in community A and 14% in community B; 36% of isolates from community A
      and 28% of isolates from community B were resistant or intermediately susceptible
      to at least 1 antibiotic tested. Reduced susceptibility was most common to
      trimethoprim-sulfamethoxazole and cefaclor (28% and 26%, respectively).
      Pneumococcal carriage (susceptible or resistant) was independently associated
      with age <5 years (odds ratio [OR]: 2.2), child care exposure (OR: 2.4), presence
      of a sibling with a positive culture (OR: 3.3), and residence in community A (OR:
      1.7). Among carriers, age <2 years (OR: 2.6), use of cephalosporins within the
      preceding 4 months (OR: 2.7), and having a sibling colonized with resistant S
      pneumoniae (OR: 5.5) were independent predictors of reduced susceptibility or
      resistance. Each pair of resistant isolates from siblings was indistinguishable
      by pulsed field gel electrophoresis and other molecular typing techniques.
      Several pneumococcal isolates from these isolated rural areas had the molecular
      characteristics of international clones of multiple-drug-resistant pneumococci
      that have been associated with worldwide spread. CONCLUSIONS: Young age and
      intrafamilial transmission were important risk factors for carriage of both
      susceptible and resistant S pneumoniae. In contrast, previous cephalosporin use
      was linked specifically to resistant pneumococcal carriage, which suggests that
      modifications in antibiotic usage patterns may have salutary effects on
      antimicrobial resistance. These results extend previous observations in large
      cities regarding the penetration of multiple-drug-resistant clones of pneumococci
      into community populations.

PMID- 11581437
TI  - Enhanced urinalysis improves identification of febrile infants ages 60 days and
      younger at low risk for serious bacterial illness.
AB  - OBJECTIVE: Investigators have sought to establish "low-risk" criteria to identify
      febrile young infants who can be observed safely without antibiotics. Previous
      studies have used criteria for standard urinalysis to identify suspected urinary
      tract infection; however, cases of urinary tract infection have been missed.
      Enhanced urinalysis, using hemocytometer cell count and Gram stain performed on
      uncentrifuged urine, has been shown to have greater sensitivity and negative
      predictive value than standard urinalysis. The objective of this study was to
      evaluate the ability of criteria that incorporate enhanced urinalysis to identify
      febrile young infants who are at low risk for serious bacterial illness (SBI).
      METHODS: Institutional guidelines were established in 1999 to evaluate in a
      retrospective cohort study infants who were </=60 days of age with temperature
      >/=38.0 degrees C. "Low-risk" criteria included 1) well appearance without focal
      infection (excluding otitis media); 2) no history of prematurity, illness, or
      previous antibiotics; 3) peripheral white blood cell count (WBC) between 5 and 15
      000/mm(3); 4) absolute band count </=1500/mm(3); 5) cerebrospinal fluid WBC
      </=5/mm(3) with a negative Gram stain; 6) enhanced urinalysis with WBC </=9/mm(3)
      with a negative Gram stain; 7) stool WBC <5/high power field in infants with
      diarrhea; and 8) chest radiograph without lobar infiltrate(s) in infants with
      respiratory signs or symptoms. SBI was defined as a lobar infiltrate on chest
      radiograph or presence of a bacterial pathogen in blood, urine, cerebrospinal
      fluid, stool, or culture obtained from the soft tissue. The hospital records of
      all infants who presented to the emergency department for evaluation of fever
      after January 1999, including those who did not meet low-risk criteria, were
      reviewed; data were collected regarding history, physical examination, laboratory
      test results, treatment, and clinical course. RESULTS: During the study period,
      434 infants presented to the emergency department for evaluation of fever. Thirty
      patients were excluded from additional analysis because of incomplete data; 60
      patients were identified immediately as "not low risk" on the basis of history or
      physical examination. Of the 344 remaining infants, 127 were identified as "low
      risk" on the basis of laboratory criteria; 83 (65.4%) were observed without
      antibiotics. None of the "low-risk" infants had an SBI. A total of 217 well
      appearing infants were classified as "not low risk" on the basis of laboratory
      criteria; 28 (12.9%) had an SBI. The overall incidence of SBI in infants with
      complete data was 10.1%, whereas the incidence of SBI in all "not low-risk"
      infants was 14.8%. The negative predictive value for the "Pittsburgh" criteria
      was 100% (95% confidence interval: 96.7%-100%); the sensitivity was 100% (95%
      confidence interval: 89.7%-100%). CONCLUSIONS: . The application of low-risk
      criteria using enhanced urinalysis improves identification of infants who are at
      low risk for SBI.

PMID- 11581438
TI  - Age of drinking onset and involvement in physical fights after drinking.
AB  - OBJECTIVE: To explore whether people who start drinking at an early age are more
      likely to have been in physical fights after drinking, independent of respondent
      history of alcohol dependence and frequency of heavy drinking. DESIGN: In 1992,
      the US Census Bureau interviewed, in person, 42 862 randomly selected adults age
      18 or older, mean age 44, household response rate 91.9%, and in-person response
      rate 97.4%. The survey included questions regarding the age respondents started
      drinking, frequency of heavy drinking, and whether respondents were ever or in
      the past year in a physical fight after drinking alcohol. RESULTS: Relative to
      respondents who did not begin drinking until age 21 or older, those who started
      drinking before age 17 were 2.9 to 4.1 times more likely ever in their lives, and
      at least 3 times more likely in the past year, to have been in a fight after
      drinking. These relationships were found even after controlling for personal
      history of alcohol dependence, years of drinking, frequency of heavy drinking,
      smoking, drug use, and other personal characteristics associated with the age
      respondents started drinking. CONCLUSIONS: An early age of drinking onset was
      associated with alcohol-related violence not only among persons under age 21 but
      among adults as well. Physicians need to query adolescent patients about the age
      they began drinking and counsel them about the increased risks associated with
      early drinking onset, such as an increased risk of being involved in alcohol
      related violence.

PMID- 11581439
TI  - Relation between infantile colic and asthma/atopy: a prospective study in an
      unselected population.
AB  - OBJECTIVE: To assess whether children with history of infantile colic may be at
      increased risk of subsequently developing asthma and/or atopy. METHODS: We used
      data collected in a large, prospective study from an unselected population.
      Infantile colic and concurrent feeding method were determined from the 2-month
      well-infant visit form completed by the physician for 983 children who were
      enrolled at birth. Markers of atopy (total serum immunoglobulin E and allergy
      skin prick test), allergic rhinitis, asthma, wheezing, and peak flow variability
      were the main outcome measures studied at different ages between infancy and 11
      years. RESULTS: Ninety (9.2%) children had infantile colic. Prevalence of colic
      was similar among children fed either breast milk or formula. There was no
      association between infantile colic and markers of atopy, asthma, allergic
      rhinitis, wheezing, or peak flow variability at any age. CONCLUSION: Our data
      cannot support the hypothesis that infantile colic provides increased risk for
      subsequent allergic disease or atopy.

PMID- 11581440
TI  - Randomized, controlled trial of oros methylphenidate once a day in children with
      attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: A new once-a-day methylphenidate (MPH) formulation, Concerta
      (methylphenidate HCl) extended-release tablets (OROS MPH), has been developed.
      This study was conducted to determine the safety and efficacy of OROS MPH in a
      multicenter, randomized, clinical trial. METHODS: Children with attention
      deficit/hyperactivity disorder (ADHD; n = 282), all subtypes, ages 6 to 12 years,
      were randomized to placebo (n = 90), immediate-release methylphenidate (IR MPH) 3
      times a day (tid; dosed every 4 hours; n = 97), or OROS MPH once a day (qd; n =
      95) in a double-blind, 28-day trial. Outcomes in multiple domains were assessed,
      and data were analyzed using analysis of variance and Kaplan Meier product limit
      estimates for time to study cessation. The primary time point for analysis was
      the last available patient visit using last observation carried forward. RESULTS:
      Children in the OROS and IR MPH groups showed significantly greater reductions in
      core ADHD symptoms than did children on placebo. This was true both at the end of
      week 1 and at the end of treatment on the basis of mean teacher and parent IOWA
      Conners ratings. IR MPH tid and OROS MPH qd did not differ significantly on any
      direct comparisons. Forty-eight percent of the placebo group discontinued early
      compared with 14% and 16% in the IR MPH and OROS MPH groups, respectively.
      CONCLUSIONS: For the treatment of core ADHD symptoms, OROS MPH dosed qd and IR
      MPH dosed tid were superior to placebo and were not significantly different from
      each other.attention-deficit/hyperactivity disorder, methylphenidate, OROS,
      Concerta.

PMID- 11581441
TI  - Excessive infant crying: the impact of varying definitions.
AB  - OBJECTIVE: To assess the impact of varying definitions of excessive crying and
      infantile colic on prevalence estimates and to assess to what extent these
      definitions comprise the same children. METHODS: Parents of 3345 infants aged 1,
      3, and 6 months (response: 96.5%) were interviewed on the crying behavior of
      their infant in a Dutch cross-sectional national population-based study. We
      computed the prevalence of excessive crying according to 10 published definitions
      regarding parent-reported duration of infant crying and the parents' experience.
      We measured concordance between pairs of definitions by Cohen's kappa (agreement
      adjusted for chance agreement). RESULTS: Overall prevalence rates of excessive
      crying varied strongly between definitions, from 1.5% to 11.9%. They were always
      highest in 1-month-old infants. Concordance between definitions was only
      excellent (kappa > 0.75) if they were closely related, such as crying for >3
      hours/day for >3 days/week for the preceding 2 or 3 weeks. Concordance between
      less closely related definitions was much weaker. Concordance between definitions
      that were based on duration and on parental experience was mostly poor (kappa:
      0.17-0.53 for infants aged 1 and 3 months). CONCLUSIONS: Different definitions of
      excessive crying lead to the inclusion of very dissimilar groups of infants. We
      recommend presenting study results using clearly described definitions,
      preferably concerning both duration of crying and parental distress. This may
      improve the comparability of studies on the cause and treatment of excessive
      infant crying. The impact of the method of data collection on this comparability
      needs additional study.colic, preventive child health care, prevention, infancy.

PMID- 11581442
TI  - The ketogenic diet: a 3- to 6-year follow-up of 150 children enrolled
      prospectively.
AB  - OBJECTIVE: To document the long-term outcome of the 83 children with difficult-to
      control seizures who were enrolled prospectively in a study of the efficacy of
      the ketogenic diet and who had remained on the diet for 1 year. METHODS: A total
      of 150 consecutive children were entered prospectively into a study of the
      ketogenic diet's efficacy and tolerability. Three to 6 years after diet
      initiation, all 150 families were sent a survey inquiring about their child's
      current health status, seizure frequency, and current anticonvulsant medications.
      They were asked about their experience with the diet and reasons for
      discontinuation. Several telephone attempts were made to contact those who did
      not respond to the written questionnaire. Responses were entered in an Access
      database and analyzed. RESULTS: In 1999, 3 to 6 years after initiating the diet,
      107 of 150 families responded to a questionnaire. Thirty-five additional families
      were interviewed by telephone, 4 were lost to follow-up, and 4 children had died,
      unrelated to the diet. Of the original 150 patient cohort, 20 (13%) were seizure
      free and an additional 21 (14%) had a 90% to 99% decrease in their seizures.
      Twenty-nine were free of medications, and 28 were on only 1 medication; 15
      remained on the diet. There were no known cardiac complications. CONCLUSION:
      Three to 6 years after initiation, the ketogenic diet had proven to be effective
      in the control of difficult-to-control seizures in children. The diet often
      allows decrease or discontinuation of medication. It is more effective than many
      of the newer anticonvulsants and is well-tolerated when it is effective.

PMID- 11581443
TI  - Who cares for medicaid-enrolled children with chronic conditions?
AB  - OBJECTIVE: To estimate generalist, pediatric subspecialist, and any subspecialist
      use by Medicaid-enrolled children with chronic conditions and to determine the
      correlates of use. METHODS: We analyzed Medicaid claims data collected from 1989
      to 1992 from 4 states for 57 328 children and adolescents with 11 chronic
      conditions. We calculated annual rates of generalist, subspecialist, and
      pediatric subspecialist use. We used logistic regression to determine the
      association of demographics, urban residence, and case-mix (Adjusted Clinical
      Groups) with the use of relevant pediatric and any subspecialist care. RESULTS:
      Most children with chronic conditions had visits to generalists (range per
      condition: 78%-90% for children with Supplemental Security Income [SSI] and 85%
      94% for children without SSI) during the year studied. Fewer children visited any
      relevant subspecialists (24%-59% for children with SSI and 13%-56% for children
      without SSI) or relevant pediatric subspecialists (10%-53% for children with SSI
      and 3%-37% for children without SSI). In general, children who were more likely
      to use pediatric subspecialists were younger, lived in urban areas, were white
      (only significant for non-SSI children), and had higher Adjusted Clinical Groups
      scores. Use of any subspecialists followed a similar pattern except that urban
      residence is statistically significant only for children with SSI and the
      youngest age group does not differ from the oldest age group for children without
      SSI. CONCLUSIONS: Children who had chronic conditions and were enrolled in
      Medicaid received a majority of their care from generalist physicians. For most
      conditions, a majority of children did not receive any relevant subspecialty care
      during the year and many of these children did not receive care form providers
      with pediatric-specific training.

PMID- 11581445
TI  - Association between sudden infant death syndrome and prone sleep position, bed
      sharing, and sleeping outside an infant crib in Alaska.
AB  - OBJECTIVE: To determine the contribution of prone sleeping, bed sharing, and
      sleeping outside an infant crib to sudden infant death syndrome (SIDS). METHODS:
      We conducted a retrospective descriptive study of all SIDS cases in Alaska from
      January 1, 1992, through December 31, 1997. Reviewed data sources included
      maternal and infant medical records, autopsy reports, birth and death
      certificates, police and state trooper death scene investigations, and
      occasionally home interviews. RESULTS: The death certificate identified SIDS as a
      cause of death for 130 infants (cause-specific infant mortality rate: 2.0 per
      1000 live births). Among infants for whom this information was known, 113 (98%)
      of 115 were found in the prone position, sleeping outside an infant crib, or
      sleeping with another person. By contrast, 2 (1.7%) were found alone and supine
      in their crib (1 of whom was found with a blanket wrapped around his face). Of 40
      infants who slept with a parent at the time of death, only 1 infant who slept
      supine with a non-drug-using parent on an adult nonwater mattress was identified.
      CONCLUSION: Almost all SIDS deaths in Alaska occurred in association with prone
      sleeping, bed sharing, or sleeping outside a crib. In the absence of other risk
      factors, SIDS deaths associated with parental bed sharing were rare.

PMID- 11581444
TI  - Estimating the cost of developmental and behavioral screening of preschool
      children in general pediatric practice.
AB  - OBJECTIVE: Despite increased recognition of the importance of development and
      growth of young children, formal developmental and behavioral screening often is
      not included in general pediatric practice. Barriers to the provision of
      developmental and behavioral screening are considerable; among them are the need
      for specialized training and uncertain reimbursement. This article develops a
      model for estimating the cost of providing pediatric developmental and behavioral
      screening that can be scaled to reflect a pediatric practice's patient population
      and choice of screening offered. METHODS: The framework for our scaleable cost
      model was drawn from work done in estimating the Resource-Based Relative Value
      Scale (RBRVS). RBRVS provides estimates of the work effort involved in the
      provision of health care services for individual Current Procedural Terminology
      codes. The American Academy of Pediatrics has assigned descriptions of pediatric
      services, including developmental and behavioral screening, to the Current
      Procedural Terminology codes originally created for adult health care services.
      The cost of conducting a screen was calculated as a function of the time and
      staff required and was loaded for practice costs using the RBRVS valuation. The
      cost of the follow-up consultation was calculated as a function of the time and
      staff required and the number of relative value units assigned in the RBRVS
      scale. RESULTS: The practice cost of providing developmental and behavioral
      screening is driven primarily by the time and staff required to conduct and
      evaluate the screens. Administration costs are lowest for parent-administered
      developmental screens ($0 if no assistance is required) and highest ($67) for
      lengthy, pediatric provider-administered screens, such as the Neonatal Behavioral
      Assessment Scale. The costs of 3 different groups of developmental and behavioral
      screening are estimated. The estimated per-member per-month cost per 0- to 3-year
      old child ranges from $4 to >$7 in our 3 examples. CONCLUSIONS: Cost remains a
      significant barrier to greater provision of formal developmental and behavioral
      screening. Our scaleable cost model may be adjusted for a given practice to
      account for the overall level of developmental risk. The model also provides an
      estimate of the time and cost of providing new screening services. This model
      allows pediatric practices to select the mix of developmental screens most
      appropriate for their particular patient population at an acceptable cost.

PMID- 11581446
TI  - Inter-neonatal intensive care unit variation in discharge timing: influence of
      apnea and feeding management.
AB  - BACKGROUND: Premature infants need to attain both medical stability and
      maturational milestones (specifically, independent thermoregulation, resolution
      of apnea of prematurity, and the ability to feed by mouth) before safe discharge
      to home. Current practice also requires premature infants to be observed in
      hospital before discharge for several days (margin of safety) after physiologic
      maturity is recognized. OBJECTIVE: To compare postmenstrual age (PMA) at
      discharge in a homogeneous population of premature infants cared for in different
      neonatal intensive care units (NICUs) and to assess the impact on hospital stay
      of the recognition and recording of physiologic maturity and the required margin
      of safety. METHODS: We studied premature infants delivered at 30 to 34 6/7 weeks
      gestational age (GA), free of significant medical or surgical complications.
      Medical records of 30 eligible infants consecutively discharged from the hospital
      before July 1997 from each of 15 NICUs in Massachusetts (9 level 2 and 6 level 3)
      were reviewed. RESULTS: A total of 435 infants were included in the study sample.
      Mean (+/- standard deviation) GA and birth weight of the study population were
      33.2 +/- 1.2 weeks and 2024 +/- 389 g, respectively. Infants were discharged at a
      similar PMA regardless of GA at birth. Considerable variation in the PMA at
      discharge between hospital sites was observed (range, 35.2 +/- 0.5 weeks to 36.5
      +/- 1.2 weeks). Despite the homogeneous study population, hospitals in which
      infants had the latest PMA at discharge also recorded mature cardiorespiratory
      and feeding behavior at an older age. Longer duration of pulse oximetry use was
      associated with later resolution of apnea. Differences in the duration of the
      margin of safety between sites did not contribute to variation in hospital stay.
      CONCLUSION: NICUs vary widely in length of hospital stay for healthy premature
      infants. We speculate that this variation results in part from differences in
      monitoring for and documentation of apnea of prematurity and feeding behavior.

PMID- 11581447
TI  - Effects of early erythropoietin therapy on the transfusion requirements of
      preterm infants below 1250 grams birth weight: a multicenter, randomized,
      controlled trial.
AB  - OBJECTIVES: Infants of </=1250 g birth weight receive multiple erythrocyte
      transfusions during their hospitalization. We hypothesized that early
      erythropoietin (Epo) and iron therapy would 1) decrease the number of
      transfusions received (infants 401-1000 g birth weight; trial 1) and 2) decrease
      the percentage of infants who received any transfusions (1001-1250 g birth
      weight; trial 2). METHODS: A total of 172 infants in trial 1 and 118 infants in
      trial 2 were randomized to treatment (Epo, 400 U/kg 3 times weekly) or
      placebo/control. Therapy was initiated by 4 days after birth and continued
      through the 35th postmenstrual week. All infants received supplemental parenteral
      and enteral iron. Complete blood and reticulocyte counts were measured weekly,
      and ferritin concentrations were measured monthly. Transfusions were administered
      according to protocol. Phlebotomy losses and transfusion data were recorded.
      RESULTS: Treated and placebo/control infants in trial 1 received a similar number
      of transfusions (4.3 +/- 3.6 vs 5.2 +/- 4.2, respectively). A similar percentage
      of treated and control infants in trial 2 received at least 1 transfusion (37% vs
      46%). Reticulocyte counts were higher in treated infants during each week of the
      study in both trials. Hematocrits were higher among treated infants from week 2
      on in both trials. Ferritin concentrations were higher in placebo/controls than
      in treated infants at weeks 4 and 8 in trial 1 and at week 4 in trial 2. No
      adverse effects of Epo or supplemental iron occurred. CONCLUSION: The combination
      of early Epo and iron as administered in this study stimulated erythropoiesis in
      infants who were </=1250 g at birth. However, the lack of impact on transfusion
      requirements fails to support routine use of early Epo.neonate, intravenous iron,
      donor exposure.

PMID- 11581448
TI  - Respiratory infections in infants: interaction of parental allergy, child care,
      and siblings-- The PIAMA study.
AB  - OBJECTIVE: To investigate the association between contacts with other children
      and the development of respiratory infections in the first year of life in
      children with or without genetic predisposition for allergy. METHODS: Children (n
      = 4146) who participate in a prospective birth cohort study (Prevention and
      Incidence of Asthma and Mite Allergy study) were investigated. Questionnaires
      were used to obtain information on doctor-diagnosed upper respiratory tract
      infection (URTI) and lower respiratory tract infection (LRTI), child care
      attendance, having siblings, family history of allergic disease, and various
      potential confounders. RESULTS: Child care attendance in the first year of life
      was associated with doctor-diagnosed URTI (adjusted odds ratio [AOR]: 2.7; 95%
      confidence interval [CI]: 2.1-3.4 for large child care facility vs no child care)
      and doctor-diagnosed LRTI (AOR: 5.6; 95% CI: 3.9-7.9). Having siblings was
      associated with doctor-diagnosed LRTI (AOR: 2.6; 95% CI: 2.0-3.4). In addition,
      children who have allergic parents and attend child care or have older siblings
      have a higher risk of developing doctor-diagnosed LRTI than do children who have
      nonallergic parents. CONCLUSIONS: Child care attendance or having siblings
      increases the risk of developing doctor-diagnosed LRTI in the first year of life
      to a greater extent in allergy-prone children than in children who are not
      allergy prone.

PMID- 11581449
TI  - Randomized, prospective study of low-dose versus high-dose inhaled nitric oxide
      in the neonate with hypoxic respiratory failure.
AB  - OBJECTIVE: There is little information on the response to very low doses of
      inhaled nitric oxide (iNO) in hypoxic near-term infants. The potential toxicities
      of iNO are dose related; thus, the ability to use lower doses safely and
      effectively may be advantageous. We hypothesized that there is no difference in
      the acute improvement in oxygenation between treatment with inhaled nitric oxide
      at 1 to 2 parts per million (ppm) or 10 to 20 ppm. METHODS: We randomized near
      term and term infants with hypoxic respiratory failure with oxygenation indices
      (OIs) of >/=10 and PaO(2) <100 on 2 separate blood gases taken at least 30
      minutes apart. Infants with congenital diaphragmatic hernia were excluded. After
      parental consent was obtained, patients were randomized to receive a starting
      nitric oxide (iNO) dose of either 1 to 2 ppm (low-dose group, n = 15) or 10 to 20
      ppm (high-dose group, n = 21). The response to iNO was assessed according to the
      increase in arterial PaO(2) and decrease in OI 30 to 60 minutes after exposure to
      the initial starting concentration. A response of <10% increase on PaO(2) and a
      <10% decrease in OI resulted in a doubling of iNO within the dose range protocol
      (1, 2, 4, and 8 ppm for the low-dose group; 10, 20, 40, and 80 ppm for the high
      dose group). RESULTS: Thirty minutes after the study gas was initiated, PaO(2)
      increased significantly overall in the low-dose (90.7 +/- 41 torr to 166.8 +/-
      95.6 torr) and high-dose (76.2 +/- 32.7 torr to 198.7 +/- 142.8 torr) groups; the
      maximal increase was seen in the infants who initially were treated with 10 ppm.
      The OI also decreased significantly overall and also was significant in the high
      dose group (21.0 +/- 13.7 to 11.4 +/- 10.4; low-dose: 18.3 +/- 7.1 to 13.2 +/-
      12.3). There was a nonsignificant fall of PaCO(2) with iNO treatment (low dose 35
      +/- 7.3 to 30 +/- 8.5 torr vs high dose 35.2 +/- 9.9 to 32.4 +/- 10.7 torr). A
      sustained response (ie, maintaining a PaO(2) and OI gain greater than 20% for the
      duration of the study gas administration) was greater in the high-dose group
      (53.3% vs 30.0%). In addition, dose increases were required more often in the low
      dose group than in the high-dose group (80.0% vs 57.1%). Among patients who did
      not respond to the initial iNO dose, 100.0% and 83.3% responded at higher doses
      of iNO for the low- and high-dose groups, respectively. There were no differences
      for death, need for extracorporeal membrane oxygenation, or other outcomes
      between the groups. CONCLUSIONS: We did not find any significant difference in
      response to low- versus high-dose iNO. An initial exposure to low-dose iNO does
      not compromise the response to higher doses if required and may result in less
      toxicity.

PMID- 11581450
TI  - Onset of jaundice in glucose-6-phosphate dehydrogenase-deficient neonates.
AB  - OBJECTIVE: We asked whether neonatal jaundice associated with glucose-6-phosphate
      dehydrogenase (G-6-PD) deficiency commences either in utero or in the immediate
      postnatal period and whether this perinatal bilirubinemia is the precursor of the
      subsequent neonatal jaundice and hyperbilirubinemia. METHODS: Mandatory serum
      total bilirubin (STB) determinations were performed within 3 hours of birth, to
      reflect the in utero state (first STB), and on the third day of life (second
      STB), with additional determinations as clinically necessary, on healthy, term
      male neonates at high risk for G-6-PD deficiency. G-6-PD Mediterranean mutation
      was determined by molecular means. G-6-PD-deficient neonates were compared with
      control participants. The relationship of first STB values to second STB and
      subsequent hyperbilirubinemia (defined as STB >/=256 micromol/L [15.0 mg/dL]) was
      determined. RESULTS: Both first and second STB values were significantly higher
      in the G-6-PD-deficient neonates (n = 52) than in control participants (n = 166;
      50 +/- 12 micromol/L vs 44 +/- 10 micromol/L [2.9 +/- 0.7 mg/dL vs 2.6 +/- 0.6
      mg/dL] and 174 +/- 52 micromol/L vs 152 +/- 52 micromol/L [10.2 +/- 3.1 mg/dL vs
      8.9 +/- 3.0 mg/dL] for the first and second STB values, respectively). The rate
      of rise between these 2 points was greater in the G-6-PD-deficient neonates (2.6
      +/- 0.9 micromol/L/h vs 2.2 +/- 0.9 micromol/L/h [0.15 +/- 0.05 mg/dL/h vs 0.13
      +/- 0.05 mg/dL/h). Sixteen (30.8%) of the G-6-PD-deficient neonates developed
      hyperbilirubinemia compared with 10 (6%) of control participants (relative risk:
      5.11; 95% confidence interval: 2.47-10.56). In both G-6-PD-deficient and normal
      populations, first STB values correlated significantly with both second STB
      values and with those who subsequently developed hyperbilirubinemia.
      Significantly more G-6-PD-deficient neonates with a first STB value greater than
      or equal to the mean developed hyperbilirubinemia compared with those with first
      STB less than the mean: 13 of 28 neonates versus 3 of 24 (relative risk: 3.7; 95%
      confidence interval: 1.20-11.51). This difference did not reach statistical
      significance in the control group. CONCLUSIONS: Higher first STB values, an
      increased risk of hyperbilirubinemia in G-6-PD-deficient neonates with first STB
      value greater than or equal to the mean, and significant correlation between
      first STB values and second STB values and hyperbilirubinemia suggest that
      jaundice in G-6-PD-deficient neonates commences in the immediate perinatal
      period, most likely in utero.

PMID- 11581451
TI  - Neonatal hemochromatosis.

PMID- 11581452
TI  - Issues in Islamic biomedical ethics: a primer for the pediatrician.
AB  - The United States is becoming increasingly pluralistic. Pediatricians must become
      familiar with the factors that affect the emotional, physical, and spiritual
      health of their patients that are outside the kin of the traditionally dominant
      value system. Although many articles have addressed the cultural and ethnic
      factors, very few have considered the impact of religion. Islam, as the largest
      and fastest-growing religion in the world, has adherent throughout the world,
      including the United States, with 50% of US Muslims being indigenous converts.
      Islam presents a complete moral, ethical, and medical framework that, while it
      sometimes concurs, at times diverges or even conflicts with the US secular
      ethical framework. This article introduces the pediatrician to the Islamic
      principles of ethics within the field of pediatric care and child-rearing. It
      demonstrates how these principles may impact outpatient and inpatient care.
      Special attention is also given to adolescent and end-of-life issues.

PMID- 11581453
TI  - National Institutes of Health Consensus Development Conference Statement:
      phenylketonuria: screening and management, October 16-18, 2000.
AB  - OBJECTIVE: To provide health care providers, patients, and the general public
      with a responsible assessment of currently available data regarding screening for
      and management of phenylketonuria (PKU). PARTICIPANTS: A nonfederal, nonadvocate,
      14-member panel representing the fields of pediatrics, genetics, human
      development, public policy, nursing, and molecular physiology and including
      patient representatives. In addition, 19 experts in pediatrics, medical genetics,
      psychology, pediatric neurology, biochemical and molecular genetics, and gene
      therapy presented data to the panel and to a conference audience of 312.
      EVIDENCE: The literature was searched using Medline for January 1980 through July
      2000, and an extensive bibliography of 3394 references was provided to the panel.
      Experts prepared abstracts for their conference presentations with relevant
      citations from the literature. Scientific evidence was given precedence over
      clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined
      questions, developed its conclusions based on the scientific evidence presented
      in open forum and the scientific literature. The panel composed a draft
      statement, which was read in its entirety and circulated to the experts and the
      audience for comment. Thereafter, the panel resolved conflicting recommendations
      and released a revised statement at the end of the conference. The panel
      finalized the revisions within a few weeks after the conference. The draft
      statement was made available on the World Wide Web immediately after its release
      at the conference and was updated with the panel's final revisions. The statement
      is available at http://consensus.nih.gov. CONCLUSIONS: Genetic testing for PKU
      has been in place for almost 40 years and has been very successful in preventing
      severe mental retardation in thousands of children and adults. Metabolic control
      is necessary across the lifespan of individuals with PKU. A comprehensive,
      multidisciplinary, integrated system is needed to delivery of care to individuals
      with PKU. Greatly needed are consistency and coordination between screening,
      treatment, data collection, and patient support programs. There should be equal
      access to culturally sensitive, age-appropriate treatment programs. Ethically
      sound, specific policies for storage, ownership, and use in future studies of
      archived samples remaining from PKU testing should be established. Research into
      the pathophysiology of PKU and relationship to genetic, neural, and behavioral
      variation is strongly encouraged. Uniform policies must be established to remove
      financial barriers to the acquisition of medical foods and modified low-protein
      foods and to provide access to support services needed to maintain metabolic
      control in individuals with PKU. Research on nondietary alternative treatments
      for PKU is strongly encouraged. To achieve optimal statistical power and cross
      cultural applicability, it will be beneficial to use data acquired via national
      and international collaboration.phenylketonuria, hyperphenylalanimea,
      phenylketonuria screening, phenylalanine-restricted diet, maternal
      phenylketonuria, newborn screening, phenylalanine monitoring, phenylketonuria
      outcomes.

PMID- 11581454
TI  - Psychopharmacology for young children: clinical needs and research opportunities.
AB  - In response to concerns about the increasing use of psychotropic medications in
      preschoolers, the National Institute of Mental Health and the Food and Drug
      Administration convened a workshop in October 2000 to examine the current state
      of knowledge regarding psychopharmacology for young children and discuss a
      variety of topics relevant to research in this age group, including safety,
      efficacy, investigational methods, and ethical aspects. The meeting gathered
      researchers, practitioners, ethicists, industry staff, and family and patient
      representatives. Efficacy and safety of psychotropics have not been
      systematically evaluated in preschoolers. The major limitation to this research
      is the diagnostic uncertainty surrounding most manifestations of psychopathology
      in early childhood. Research in developmental psychopathology is needed to
      clarify diagnosis and provide sensitive and specific methods for clinical trials.
      Possible approaches to expanding the research basis of this area of clinical
      practice, including a recently started study of methylphenidate in preschoolers,
      are reported here.

PMID- 11581455
TI  - Should we be teaching residents how to bill for their outpatient services?

PMID- 11581456
TI  - Uncertainty in the management of viral lower respiratory tract disease.

PMID- 11581457
TI  - Influenza virus continues to pose new challenges.

PMID- 11581458
TI  - Sedation, risk, and safety: do we really have data at last?

PMID- 11581459
TI  - Femur fracture in infants: a possible accidental etiology.
AB  - Femoral fractures in nonambulating infants are generally felt to be attributable
      to abuse in the absence of significant trauma or underlying organic pathology.
      The investigation of such fractures includes a report to appropriate social
      service and law enforcement agencies, and legal involvement. This paper describes
      2 nonambulatory infants who sustained identical oblique distal femoral
      metaphyseal fractures extending through the growth plate after playing in an
      infant stationary activity center called an Exersaucer. It is possible that the
      twisting motion provided by the Exersaucer (Evenflo, Picqua, OH) might be
      consistent with the generation of forces necessary to cause these fractures.

PMID- 11581460
TI  - Bladder retention of urine as a result of continuous intravenous infusion of
      fentanyl: 2 case reports.
AB  - Sedation has been commonly used in the neonate to decrease the stress and pain
      from the noxious stimuli and invasive procedures in the neonatal intensive care
      unit, as well as to facilitate synchrony between ventilator and spontaneous
      breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal
      intensive care unit setting for these very purposes. Various reported side
      effects of fentanyl administration include chest wall rigidity, hypotension,
      respiratory depression, and bradycardia. Here, 2 cases of urinary bladder
      retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a
      result of continuous infusion of fentanyl are reported.

PMID- 11581461
TI  - Prevention of agricultural injuries among children and adolescents.
AB  - Although the annual number of farm deaths to children and adolescents has
      decreased since publication of the 1988 American Academy of Pediatrics statement,
      "Rural Injuries," the rate of nonfatal farm injuries has increased. Approximately
      100 unintentional injury deaths occur annually to children and adolescents on US
      farms, and an additional 22 000 injuries to children younger than 20 years occur
      on farms. Relatively few adolescents are employed on farms compared with other
      types of industry, yet the proportion of fatalities in agriculture is higher than
      that for any other type of adolescent employment. The high mortality and severe
      morbidity associated with farm injuries require continuing and improved injury
      control strategies. This statement provides recommendations for pediatricians
      regarding patient and community education as well as public advocacy related to
      agricultural injury prevention in childhood and adolescence.

PMID- 11581462
TI  - Acetaminophen toxicity in children.
AB  - Acetaminophen is widely used in children, because its safety and efficacy are
      well established. Although the risk of developing toxic reactions to
      acetaminophen appears to be lower in children than in adults, such reactions
      occur in pediatric patients from intentional overdoses. Less frequently,
      acetaminophen toxicity is attributable to unintended inappropriate dosing or the
      failure to recognize children at increased risk in whom standard acetaminophen
      doses have been administered. Because the symptoms of acetaminophen intoxication
      are nonspecific, the diagnosis and treatment of acetaminophen intoxication are
      more likely to be delayed in unintentional cases of toxicity. This statement
      describes situations and conditions that may contribute to acetaminophen toxicity
      not associated with suicidal intentions.

PMID- 11581463
TI  - Improving substance abuse prevention, assessment, and treatment financing for
      children and adolescents.
AB  - The numbers of children, adolescents, and families affected by substance abuse
      have sharply increased since the early 1990s. The American Academy of Pediatrics
      recognizes the scope and urgency of this problem and has developed this policy
      statement for consideration by Congress, federal and state agencies, employers,
      national organizations, health care professionals, health insurers, managed care
      organizations, advocacy groups, and families.

PMID- 11581464
TI  - Bicycle helmets.
AB  - Bicycling remains one of the most popular recreational sports among children in
      America and is the leading cause of recreational sports injuries treated in
      emergency departments. An estimated 23 000 children younger than 21 years
      sustained head injuries (excluding the face) while bicycling in 1998. The bicycle
      helmet is a very effective device that can prevent the occurrence of up to 88% of
      serious brain injuries. Despite this, most children do not wear a helmet each
      time they ride a bicycle, and adolescents are particularly resistant to helmet
      use. Recently, a group of national experts and government agencies renewed the
      call for all bicyclists to wear helmets. This policy statement describes the role
      of the pediatrician in helping attain universal helmet use among children and
      teens for each bicycle ride.

PMID- 11581465
TI  - Clinical practice guideline: treatment of the school-aged child with attention
      deficit/hyperactivity disorder.
AB  - This clinical practice guideline provides evidence-based recommendations for the
      treatment of children diagnosed with attention-deficit/hyperactivity disorder
      (ADHD). This guideline, the second in a set of policies on this condition, is
      intended for use by clinicians working in primary care settings. The initiation
      of treatment requires the accurate establishment of a diagnosis of ADHD; the
      American Academy of Pediatrics (AAP) clinical practice guideline on diagnosis of
      children with ADHD(1) provides direction in appropriately diagnosing this
      disorder. The AAP Committee on Quality Improvement selected a subcommittee
      composed of primary care and developmental-behavioral pediatricians and other
      experts in the fields of neurology, psychology, child psychiatry, education,
      family practice, and epidemiology. The subcommittee partnered with the Agency for
      Healthcare Research and Quality and the Evidence-based Practice Center at
      McMaster University, Ontario, Canada, to develop the evidence base of literature
      on this topic.(2) The resulting systematic review, along with other major studies
      in this area, was used to formulate recommendations for treatment of children
      with ADHD. The subcommittee also reviewed the multimodal treatment study of
      children with ADHD(3) and the Canadian Coordinating Office for Health Technology
      Assessment report (CCOHTA).(4) Subcommittee decisions were made by consensus
      where definitive evidence was not available. The subcommittee report underwent
      extensive review by sections and committees of the AAP as well as by numerous
      external organizations before approval from the AAP Board of Directors. The
      guideline contains the following recommendations for the treatment of a child
      diagnosed with ADHD:

PMID- 11581466
TI  - No evidence for a new variant of measles-mumps-rubella-induced autism.
AB  - OBJECTIVE: A link has been postulated between measles-mumps-rubella (MMR) vaccine
      and a form of autism that is a combination of developmental regression and
      gastrointestinal symptoms that occur shortly after immunization. This hypothesis
      has involved 3 separate claims: 1) that there is new phenotype of autism
      involving regression and gastrointestinal symptoms, 2) that this new variant is
      responsible for the alleged rise of autism rates, and 3) that this phenotype is
      associated with biological findings suggestive of the persistence of measles
      infection. We tested the first of these claims. If this new "autistic
      enterocolitis" syndrome had some validity, then 1 or several of the following 6
      predictions should be supported by empirical data: 1) childhood disintegrative
      disorder has become more frequent, 2) the mean age of first parental concern for
      autistic children who are exposed to MMR is closer to the mean immunization age
      than in children who are not exposed to MMR, 3) regression in the development of
      children with autism has become more common in MMR-vaccinated children, 4) the
      age of onset for autistic children with regression clusters around the MMR
      immunization date and is different from that of autistic children without
      regression, 5) children with regressive autism have distinct symptom and severity
      profiles, and 6) regressive autism is associated with gastrointestinal symptoms
      and/or inflammatory bowel disorder. METHODS: Three samples were used.
      Epidemiologic data on 96 children (95 immunized with MMR at a median age of 13.5
      months) who were born between 1992 and 1995 and had a pervasive developmental
      disorder diagnosis as reported in a recent UK survey (post-MMR sample) were
      compared with data from 2 previous clinical samples (1 pre-MMR [n = 98] and 1
      post-MMR [n = 68]) of autistic patients. All patients were assessed with the
      standardized Autism Diagnostic Interview (ADI), allowing rigorous comparison of
      age at first parental concerns and rates of regression across samples.
      Reliability was excellent on ADI scores, age of parental concern, and
      developmental regression. Furthermore, data on bowel symptoms and disorders were
      available in the epidemiologic survey from both pediatric and parental sources,
      and immunization dates were obtained from computerized records. RESULTS: The
      prevalence of childhood disintegrative disorder was 0.6/10 000 (95% confidence
      interval: 0.02-3.6/10 000); this very low rate is consistent with previous
      estimates and is not suggestive of an increased frequency of this form of
      pervasive developmental disorder in samples of children who are immunized with
      MMR. There was no difference in the mean age at first parental concern between
      the 2 samples exposed to MMR (19.3 and 19.2 months) and the pre-MMR sample (19.5
      months). Thus, MMR immunization was not associated with a shift toward an earlier
      age for first parental concerns. Similarly, the rate of developmental regression
      reported in the post-MMR sample (15.6%) was not different from that in the pre
      MMR sample (18.4%); therefore, there was no suggestion that regression in the
      developmental course of autism had increased in frequency since MMR was
      introduced. In the epidemiologic sample, the subset of autistic children with
      regression had no other developmental or clinical characteristics, which would
      have argued for a specific, etiologically distinct phenotype. Parents of autistic
      children with developmental regression detected the first symptoms at a very
      similar age (19.8 months) to those of autistic children without regression (19.3
      months). Moreover, the mean intervals from MMR immunization to parental
      recognition of autistic symptoms were comparable in autistic children with or
      without regression (248 vs 272 days; not significant). In the epidemiologic
      sample, gastrointestinal symptoms were reported in 18.8% of children.
      Constipation was the most common symptom (9.4%), and no inflammatory bowel
      disorder was reported. Furthermore, there was no association between
      developmental regression and gastrointestinal symptoms (odds ratio: 0.63; 95%
      confidence interval: 0.06-3.2; not significant), and only 2.1% of the sample
      experienced both problems, a rate that did not exceed chance expectations.
      CONCLUSIONS: No evidence was found to support a distinct syndrome of MMR-induced
      autism or of "autistic enterocolitis." These results add to the recent
      accumulation of large-scale epidemiologic studies that all failed to support an
      association between MMR and autism at population level. When combined, the
      current findings do not argue for changes in current immunization programs and
      recommendations.

PMID- 11581467
TI  - Hemolytic-Uremic Syndrome and Escherichia coli O121 at a Lake in Connecticut,
      1999.
AB  - OBJECTIVE: Non-O157 Shiga toxin-producing Escherichia coli (STEC) have emerged as
      an important public health problem. Outbreaks attributed to non-O157 STEC rarely
      are reported. In 1999, follow-up of routine surveillance reports of children with
      hemolytic- uremic syndrome (HUS) identified a small cluster of 3 cases of HUS,
      all of whom had spent overlapping time in a Connecticut lake community in the
      week before onset of symptoms. We conducted an investigation to determine the
      magnitude and source of the outbreak and to determine risk factors associated
      with the transmission of illness. METHODS: We conducted a cohort study and an
      environmental investigation. The study population included all people who were at
      the lake in a defined geographic area during July 16-25, 1999. This time and area
      were chosen on the basis of interviews with the 3 HUS case-patients. A case was
      defined as diarrhea (>/=3 loose stools/d for >/=3 days) in a person who was at
      the lake during July 16-25, 1999. Stool samples were requested from any lake
      resident with diarrheal illness. Stools were cultured for Salmonella, Shigella,
      Campylobacter, and E coli O157. Broth cultures of stools were tested for Shiga
      toxin. Case-patients were asked to submit a serum specimen for antibody testing
      to lipopolysaccharides of selected STEC. Environmental samples from sediment,
      drinking water, lake water, and ice were obtained and cultured for E coli and
      tested for Shiga toxin. An environmental evaluation of the lake was conducted to
      identify any septic, water supply system, or other environmental condition that
      could be related to the outbreak. RESULTS: Information was obtained for 436
      people from 165 (78%) households. Eleven (2.5%) people had illnesses that met the
      case definition, including the 3 children with HUS. The attack rate was highest
      among those who were younger than 10 years and who swam in the lake on July 17 or
      18 (12%; relative risk [RR]: 7.3). Illness was associated with swimming (RR =
      8.3) and with swallowing water while swimming (RR = 7.0) on these days. No person
      who swam only after July 18 developed illness. Clinical characteristics of case
      patients included fever (27%), bloody diarrhea (27%), and severe abdominal
      cramping (73%). Only the 3 children with HUS required hospitalization. No
      bacterial pathogen was isolated from the stool of any case-patient. Among lake
      residents outside the study area, E coli O121:H19 was obtained from a Shiga toxin
      producing isolate from a toddler who swam in the lake. Serum was obtained from 7
      of 11 case-patients. Six of 7 case-patients had E coli O121 antibody titers that
      ranged from 1:320 to >1:20 480. E coli indicative of fecal contamination was
      identified from sediment and water samples taken from a storm drain that emptied
      into the beach area and from a stream bed located between 2 houses, but no Shiga
      toxin-producing strain was identified. CONCLUSIONS: Our findings are consistent
      with a transient local beach contamination in mid-July, probably with E coli
      O121:H19, which seems to be able to cause severe illness. Without HUS
      surveillance, this outbreak may have gone undetected by public health officials.
      This outbreak might have been detected sooner if Shiga toxin screening had been
      conducted routinely in HUS cases. Laboratory testing that relies solely on the
      inability of an isolate to ferment sorbitol will miss non-O157 STEC, such as E
      coli O121. Serologic testing can be used as an adjunct in the diagnosis of STEC
      infections. Lake-specific recommendations included education, frequent water
      sampling, and alternative means for toddlers to use lake facilities.

PMID- 11581468
TI  - Haemophilus influenzae Type b disease among Amish children in Pennsylvania:
      reasons for persistent disease.
AB  - OBJECTIVE: To identify reservoirs of Haemophilus influenzae type b (Hib)
      pharyngeal carriage and assess barriers to vaccination among 2 Amish communities
      in Pennsylvania. METHODS: We investigated recent cases, performed community
      surveys for Hib vaccination coverage and pharyngeal carriage, and administered a
      questionnaire assessing vaccination knowledge and attitudes to 298 members of 2
      Amish communities (A and B) in Pennsylvania and, as a comparison group, 136 non
      Amish family members who participated in state immunization clinics. From
      December 1999 to February 2000, 8 cases of invasive Hib disease occurred among
      children who were 5 years of age or younger in Pennsylvania. Six of the case
      patients were from Amish communities. None of the children had been vaccinated.
      RESULTS: Among children who were 5 years of age or younger, Hib vaccine coverage
      was low in the 2 Amish communities: A (9 [28%] of 32) and B (3 [7%] of 41)
      compared with the non-Amish group (19 [95%] of 20). Hib carriage prevalence was
      higher in both Amish communities than in the non-Amish group (A: 3%; B: 8%; non
      Amish: 0%). More households in community B had 1 or more Hib carriers than in
      community A (8 [28%] of 29 vs 3 [9%] of 32). Among Amish parents who did not
      vaccinate their children, only 25% (13 of 51) identified either religious or
      philosophical objections as a factor; 51% (26 of 51) reported that vaccinating
      was not a priority compared with other activities of daily life. Seventy-three
      percent (36 of 49) would vaccinate their children if vaccination were offered
      locally. CONCLUSIONS: Undervaccinated communities in the United States still
      exist and allow circulation of Hib strains, resulting in disease among
      susceptible children. Identification of undervaccinated populations, such as the
      Amish, and targeted education and vaccination campaigns are essential to
      achieving elimination of Hib disease.

PMID- 11581469
TI  - Reactive hyperemia and interleukin 6, interleukin 8, and tumor necrosis factor
      alpha in the diagnosis of early-onset neonatal sepsis.
AB  - OBJECTIVE: To evaluate the diagnostic value of peripheral circulatory reactive
      hyperemia and serum levels of interleukin-6 (IL-6), IL-8, and tumor necrosis
      factor-alpha (TNF-alpha) in early-onset neonatal sepsis. METHODS: Reactive
      hyperemia in the dorsal hand and serum levels of IL-6, IL-8, and TNF-alpha were
      studied in newborn infants (n = 32; gestational age 39 +/- 3 weeks) who had been
      admitted to the neonatal unit because of suspected sepsis <48 hours after birth.
      On admission, reactive hyperemia after a standardized arterial occlusion was
      measured with laser Doppler technique, and blood samples were taken for cytokine
      analyses. On the basis of predetermined criteria, the infants subsequently were
      classified as septic (n = 12) or not (n = 20). RESULTS: The degree of reactive
      hyperemia was higher in the group with sepsis (median + 170% perfusion increase)
      than in that without (+37%). On admission, serum levels of IL-6, IL-8, and TNF
      alpha all were higher in septic (median values: 1620, 331, and 22 pg/mL,
      respectively) than in nonseptic neonates (median values: 42, 63, and 13 pg/mL,
      respectively). In the group with sepsis, the degree of reactive hyperemia
      correlated to log IL-6 (r = 0.80) and log IL-8 values (r = 0.71). CONCLUSION:
      Newborn infants with septicemia have increased reactive hyperemia and elevated
      cytokine levels very early in their disease. Reactive hyperemia in skin can be
      analyzed at the bedside and noninvasively and therefore may serve as an
      additional diagnostic tool in neonatal sepsis.

PMID- 11581470
TI  - Preimmunization anti-pneumococcal antibody levels are protective in a majority of
      patients with cystic fibrosis.
AB  - OBJECTIVE: Although invasive pneumococcal disease is infrequent in cystic
      fibrosis (CF), it is recommended that all patients with CF receive pneumococcal
      immunization. As part of a comprehensive program to immunize our clinic
      population, we obtained preimmunization anti-pneumococcal antibody levels. We
      hypothesized that the percentage of CF patients without protective levels of anti
      pneumococcal antibody levels would be high, as they are exposed to frequent
      antibiotic therapy that may eradicate organisms before generation of an antibody
      response. METHODS: An observational study of 100 patients with CF, aged 1 to 39
      years, was conducted in a regional CF center. Preimmunization anti-pneumococcal
      antibody levels against 6 serotypes were measured by enzyme-linked immunosorbent
      assay. Protective antibody levels were defined as >200 ng/mL. RESULTS: A majority
      of CF patients-61% to 100%, depending on age and serotype-had protective levels
      of pneumococcal antibody. There was a significant positive correlation between
      antibody level and age for 5 of the 6 serotypes tested. CONCLUSIONS: In
      contradistinction to our hypothesis, the majority of CF patients have protective
      preimmunization anti-pneumococcal antibody levels. However, a significant
      proportion-between 17% and 39%, depending on the serotype-did not exhibit
      adequate levels. Therefore, we concur with current recommendations for
      pneumococcal immunization in CF.

PMID- 11581471
TI  - Influenza A infection is an important cause of febrile seizures.
AB  - OBJECTIVES: To compare the incidence of febrile seizures in children hospitalized
      for influenza A infection with parainfluenza and adenovirus infection and to
      examine the hypothesis that children hospitalized for influenza A (variant
      Sydney/H3N2) during the 1998 season in Hong Kong had more frequent and refractory
      seizures when compared with other respiratory viruses, including the A/Wuhan H3N2
      variant that was present in the previous year. METHODS: Medical records of
      children between 6 months and 5 years of age admitted for influenza A infection
      in 1998 were reviewed. For comparison, records of children of the same age group
      with influenza A infection in 1997, and with parainfluenza and adenovirus
      infections between 1996 and 1998 were reviewed. Children who were afebrile or who
      had an underlying neurologic disorder were excluded. RESULTS: Of children
      hospitalized for influenza A in 1998 and 1997, 54/272 (19.9%) and 27/144 (18.8%)
      had febrile seizures, respectively. The overall incidence of febrile seizures
      associated with influenza A (19.5%) was higher than that in children hospitalized
      for parainfluenza (18/148; 12.2%) and adenovirus (18/199; 9%) infection,
      respectively. In children who had febrile seizures, repeated seizures were more
      commonly associated with influenza A infection than with parainfluenza or
      adenovirus infection (23/81 [28%] vs 3/36 [8.3%], odds ratio [OR] 4.3, 95%
      confidence interval: 1.2 to 15.4). Alternatively, children with influenza A
      infection had a higher incidence (23/416, 5.5%) of multiple seizures during the
      same illness than those with adenovirus or parainfluenza infection (3/347, 0.86%;
      OR 6.7, 95% confidence interval: 2.0-22.5.) The increased incidence of febrile
      seizures associated with influenza A was not attributable to differences in age,
      gender, or family history of febrile seizure. Multivariate analysis, adjusted for
      peak temperature and duration of fever, showed that hospitalized children
      infected with infection A had a higher risk of febrile seizures than those who
      were infected with parainfluenza or adenovirus (OR 1.97). Influenza A infection
      was a significant cause of febrile seizure admissions. Of 250 and 249 children
      admitted to Queen Mary Hospital for febrile seizures in 1997 and 1998,
      respectively, influenza A infection accounted for 27 (10.8%) admissions in 1997
      and 54 (21.7%) in 1998. During months of peak influenza activity, it accounted
      for up to 35% to 44% of febrile seizure admissions. In contrast, parainfluenza,
      adenovirus, respiratory syncytial virus, and influenza B had a smaller
      contribution to hospitalizations for febrile seizures, together accounting for
      only 25/250 (10%) admissions in 1997 and 16/249 (6.4%) in 1998. CONCLUSION: The
      influenza A Sydney variant (H3N2) was not associated with an increased risk of
      febrile seizures when compared with the previous influenza A Wuhan variant (H3N2)
      or H1N1 viruses. However, in hospitalized children, influenza A is associated
      with a higher incidence of febrile seizures and of repeated seizures in the same
      febrile episode than are adenovirus or parainfluenza infections. The pathogenesis
      of these observations warrants additional studies. Complex febrile seizures,
      particularly multiple febrile seizures at the time of presentation, have been
      thought to carry an adverse long-term prognosis because of its association with a
      higher incidence of epilepsy. Repeated febrile seizures alone, particularly if
      associated with influenza A infection, may not be as worrisome as children with
      complex febrile seizures because of other causes, which requires additional
      investigation. This may subsequently have an impact on reducing the burden of
      evaluation in a subset of children with complex febrile seizures.

PMID- 11581472
TI  - Limb deficiencies in newborn infants.
AB  - OBJECTIVE: The prevalence rate of all types of limb reduction defects in general
      and those that potentially are caused by vascular disruption in particular is
      needed to provide a baseline for the evaluation of infants who are exposed in
      utero to teratogens that cause vascular disruption. The objective of this study
      was to determine this prevalence rate. METHODS: All infants with any limb
      deficiency among 161 252 liveborn and stillborn infants and elective terminations
      were identified in a hospital-based Active Malformations Surveillance Program in
      Boston in the years 1972 to 1974 and 1979 to 1994. An extensive search was made
      to identify infants who were missed by the Surveillance Program; an additional 8
      infants (7.3% of total) were identified. The limb reduction defects were
      classified in 3 ways: 1) by the anatomic location of the defect, that is
      longitudinal, terminal, intercalary, etc; 2) for infants with absence/hypoplasia
      of fingers or toes, a tabulation of which digit or digits were affected; and 3)
      by apparent cause. RESULTS: The prevalence rate for all types of limb deficiency
      was 0.69/1000. The apparent causes included single mutant genes, familial
      occurrence, and known syndromes (24%); chromosome abnormalities (6%); teratogens
      (4%); vascular disruption (35%); and unknown cause (32%). CONCLUSIONS: A hospital
      based surveillance program can be used to establish the prevalence of limb
      reduction defects, if ascertainment is extended to include elective terminations
      for fetal abnormalities. An apparent cause can be established for most limb
      defects when the clinical findings are used rather than reliance only on the
      International Classification of Diseases, Ninth Revision, codes of the discharge
      diagnoses. The prevalence rate of limb reduction defects as a result of presumed
      vascular disruption was 0.22/1000.

PMID- 11581473
TI  - Sex differences in the secular changes in pubertal maturation.
AB  - OBJECTIVE: It is a common experience among pediatricians in the industrialized
      countries that many girls-but many fewer boys-present with secondary sex
      characteristics at a younger age than normal. This study examines whether there
      are sex differences in the secular changes toward earlier pubertal maturation.
      METHODS: The author collected the growth data from various studies performed in
      Greece in the 20th century (from 1928 to 1995) and estimated the age at peak
      annual height increment in each study by calculating mean increase in height in
      each successive year. RESULTS: In all studies, boys presented peak mean annual
      height increment at 13 to 14 years of age. Girls did not present a discernible
      peak height increment until the late 1960s; however, thereafter they presented a
      peak height increment at 11 to 12 years of age. CONCLUSIONS: The data suggest sex
      differences in the secular changes in pubertal maturation, girls being affected
      more intensely than boys.

PMID- 11581474
TI  - Breastfeeding and early weaning practices in northeast Brazil: a longitudinal
      study.
AB  - OBJECTIVES: To describe breastfeeding practices from 0 to 12 months of age in 4
      small towns that are representative of urban northeast Brazil and to identify
      factors associated with introduction of other milk in the first month of life.
      METHODS: From January to August 1998, 364 mothers were interviewed at delivery to
      ascertain antenatal care; delivery room practices; and their intentions regarding
      breastfeeding, pacifiers, and introduction of water, teas, and other milk. Their
      perceptions of home support and the advantages of breastfeeding also were
      assessed. Thereafter, daily information about feeding practices was collected at
      twice-weekly home visits. When other milk was started, a second interview was
      conducted to ascertain initial and current breastfeeding problems and use of a
      pacifier. Reasons for starting other milk were investigated using 5-point Likert
      scales. RESULTS: Mothers were positive toward breastfeeding, and 99% breastfed
      their new infant. Few intended to breastfeed exclusively, and in the first week
      80% gave water/tea and 56% used a pacifier. The median duration of exclusive
      breastfeeding was 0 days, and the median age for starting other milk was 24 days.
      The median duration of breastfeeding was 65 days for mothers who started other
      milk within 1 month and 165 days for other mothers. After adjustment for
      confounding variables, the main factors associated with introduction of other
      milk within 1 month were pacifier use in the first week (odds ratio [OR], 4.01;
      95% confidence interval [CI]: 2.07-7.78), intention to start other milk in the
      first month (OR, 3.79; 95% CI: 1.74-8.24), giving water/tea in the first week
      (OR, 3.07; 95% CI: 1.56-6.03), and leaving the maternity ward before
      breastfeeding was started (OR, 2.59; 95% CI: 1.34-5.04). CONCLUSION: Although
      breastfeeding is common in this community, it rarely is exclusive and takes place
      for a relatively short duration. Identification of risk factors for early
      introduction of other milk offers potential avenues for future intervention,
      including improvement of breastfeeding support in antenatal and maternity
      services.

PMID- 11581475
TI  - Exclusive breastfeeding reduces acute respiratory infection and diarrhea deaths
      among infants in Dhaka slums.
AB  - OBJECTIVES: To describe breastfeeding practices and investigate the influence of
      exclusive breastfeeding in early infancy on the risk of infant deaths, especially
      those attributable to respiratory infections (ARI) and diarrhea. METHODS: A
      prospective observational study was conducted on a birth cohort of 1677 infants
      who were born in slum areas of Dhaka in Bangladesh and followed from birth to 12
      months of age. After enrollment at birth, the infants were visited 5 more times
      by 12 months of age. Verbal autopsy, based on a structured questionnaire, was
      used to assign a cause to the 180 reported deaths. Proportional hazards
      regression models were used to estimate the effect of breastfeeding practices,
      introduced as a time-varying variable, after accounting for other variables,
      including birth weight. Overall neonatal, postneonatal and infant mortality, and
      mortality attributable to ARI and diarrhea were measured. RESULTS: The proportion
      of infants who were breastfed exclusively was only 6% at enrollment, increasing
      to 53% at 1 month and then gradually declining to 5% at 6 months of age.
      Predominant breastfeeding declined from 66% at enrollment to 4% at 12 months of
      age. Very few infants were not breastfed, whereas the proportion of partially
      breastfed infants increased with age. Breastfeeding practices did not differ
      between low and normal birth weight infants at any age. The overall infant
      mortality rate was 114 deaths per 1000 live births. Compared with exclusive
      breastfeeding in the first few months of life, partial or no breastfeeding was
      associated with a 2.23-fold higher risk of infant deaths resulting from all
      causes and 2.40- and 3.94-fold higher risk of deaths attributable to ARI and
      diarrhea, respectively. CONCLUSION: The important role of appropriate
      breastfeeding practices in the survival of infants is clear from this analysis.
      The reduction of ARI deaths underscores the broad-based beneficial effect of
      exclusive breastfeeding in prevention of infectious diseases beyond its role in
      reducing exposure to contaminated food, which may have contributed to the strong
      protection against diarrhea deaths.

PMID- 11581476
TI  - Neonatal screening for congenital adrenal hyperplasia: 17-hydroxyprogesterone
      levels and CYP21 genotypes in preterm infants.
AB  - OBJECTIVE: Neonatal screening for congenital adrenal hyperplasia (CAH) among
      preterm infants is complicated by the fact that healthy preterm infants have
      higher levels of 17-hydroxyprogesterone (17-OHP) than term infants, resulting in
      a higher false-positive rate. Even when gestational age-related cutoff levels
      after ether extraction were used, the false-positive cases primarily comprised
      preterm infants. The aim of the study was to optimize the procedure for neonatal
      screening for CAH in preterm infants. METHODS: The 17-OHP levels in 6200 preterm
      infants were correlated to the gestational age. We also calculated the number of
      recalls for different putative cutoff levels of the 17-OHP by direct assay and
      after extraction in 1275 preterm infants who represented the most elevated cases
      in a population of approximately 30 000 preterm infants. The CYP21 genotypes and
      screening levels were determined in the 12 preterm infants with CAH diagnosed
      since the start of screening. The effect of possible interfering factors such as
      gestational age, neonatal stress, and prenatal glucocorticoid treatment for
      pulmonary maturation was studied. RESULTS: The extraction procedure did not
      significantly improve the sensitivity or specificity of the screening, whereas it
      delayed the day of recall from 8 to 13 days (median). We could not demonstrate
      any systematic influence of the studied stress factors or the prenatal
      glucocorticoid treatment on the 17-OHP screening levels. In the patients with
      CAH, the 17-OHP levels correlated better with disease severity than with the
      degree of prematurity. CONCLUSIONS: On the basis of these results, we omitted the
      extraction step and changed the cutoff levels in the Swedish screening program
      for preterm infants. We chose to use a cutoff level of 400 nmol/L plasma in
      infants who were born before week 35 and 150 nmol/L for infants who were born in
      weeks 35 and 36. For detecting more patients, the cutoff level would have to be
      much lower, which would result in a number of false-positive tests that we
      consider to be unacceptably high. It is clear that neonatal screening cannot
      detect all infants with CAH. Some milder forms of the disease, just like in the
      past, will have to be diagnosed on the basis of clinical signs and symptoms.

PMID- 11581477
TI  - Onset and persistence of childhood asthma: predictors from infancy.
AB  - OBJECTIVE: In a prospective study of children with a family history of asthma,
      asthma onset by 3 years of age was found previously to be positively associated
      with variables from the first year of life, including elevated total
      immunoglobulin E (IgE), frequent respiratory infections, and parenting
      difficulties. We followed this cohort of genetically at-risk children to
      investigate the relationship between factors assessed in infancy and asthma,
      allergy, and psychological status at school age. METHODS: A cohort of 150
      children who were at risk for developing asthma were identified prenatally on the
      basis of the mothers' having asthma. For 28 children, the father had asthma as
      well, putting them at bilateral genetic risk. Families primarily were middle and
      upper middle class Caucasians. Parents came to the clinic during the third
      trimester of pregnancy for assessments of medical and psychosocial functioning. A
      home visit took place when the infant was 3 weeks old, when parenting risk was
      assessed before the onset of any asthma symptoms. Parenting difficulties included
      problems with infant caregiving as well as components of maternal functioning,
      such as postpartum depression and inadequate marital support. Blood was drawn for
      serum IgE at 6 months of age. Parents and offspring subsequently came to the
      clinic multiple times, with the last clinic visit during the child's sixth year.
      Follow-up at age 6 involved a clinic visit for allergy and psychosocial
      evaluations, consisting of interviews and a behavior questionnaire. Seventy-seven
      children received the allergy and psychosocial evaluation, 26 received the
      psychosocial evaluation in the clinic, and 30 families received telephone
      interviews and mailed in questionnaires. Additional monitoring of families by
      telephone and mail was maintained over the next 2 years, until the children were
      8, to ensure accurate characterization of the course of illness. Comprehensive
      medical records were obtained and reviewed for all health care contacts. Children
      were designated as having asthma when there was documentation in medical records
      of physician-diagnosed asthma, observed wheezing, and/or prescription of asthma
      medications during the time period when the child was between 6 and 8 years of
      age. Parental reports of the occurrence of asthma corroborated the medical record
      data. RESULTS: Data regarding asthma status were available for 145 children
      through 8 years of age. Forty (28%) of the children manifested asthma between 6
      and 8 years of age. Among variables previously reported to predict asthma onset
      by age 3, 3 proved to have significant univariate relationships with asthma
      between ages 6 and 8: elevated IgE levels measured when the children were 6
      months of age, global ratings of parenting difficulties measured when infants
      were 3 weeks old, and higher numbers of respiratory infections in the first year
      of life. Among these offspring of mothers with asthma, paternal asthma showed a
      significant association with asthma between ages 6 and 8. Eczema in the first
      year was not significantly related to later asthma. Multiple logistic regression
      showed that the model that best predicted asthma at ages 6 to 8 from infancy
      variables included 2 main effects. The adjusted odds ratio for 6-month IgE was
      2.15 (1.51, 3.05) and for parenting difficulties was 2.07 (1.15, 3.71). Although
      socioeconomic status (SES) was not associated with asthma at ages 6 to 8,
      families of lower SES were more likely to be rated as having parenting
      difficulties early in the child's life. The mothers of lower SES breastfed for a
      shorter period of time and were more likely to smoke during their infant's first
      year. There were more respiratory infections during the first year of life among
      infants whose mother was rated as having more parenting difficulties. Mothers who
      reported smoking breastfed their infants for a shorter length of time. Male
      gender was significantly associated with higher IgE levels when infants were 6
      months of age. Laboratory testing was completed for 77 children at age 6. Total
      serum IgE levels were significantly higher for the children with asthma between
      ages 6 and 8. Skin-prick testing showed that the children with asthma had
      significantly more positive skin test reactions than did the children without
      asthma. Psychosocial interview data at 6 years of age were available for 103
      families, and behavioral questionnaires were available for 133 families. On the
      basis of 6-year interviews, children with asthma were rated as being at greater
      psychological risk than were the children without asthma. Mothers' Child Behavior
      Checklist (CBCL) ratings of their children's behavior indicated higher
      internalizing scores for the children with asthma as compared with the children
      without asthma. Like the 6-month IgE, 6-year IgE was higher for boys. IgE levels
      measured at 6 months of age were significantly correlated with 6-year IgE levels.
      Parenting difficulties measured at 3 weeks were significantly correlated with 6
      year measures of maternal depression, CBCL Internalizing score, and Child
      Psychological Risk (CPR) score. There also were significant correlations among
      the psychosocial variables assessed when the children were 6 years of age;
      maternal depression was significantly associated with child CBCL Internalizing
      score and CPR score, and the last 2 also were significantly correlated. Multiple
      logistic regression showed that 2 concurrently measured variables entered the
      model showing the strongest associations with asthma at ages 6 to 8. The adjusted
      odds ratio for CPR score was 3.21 (1.29-7.96) and for 6-year IgE was 1.71 (1.04
      2.80). CONCLUSIONS: This study of the natural history of childhood asthma focused
      on the development of asthma into the school-age years in a genetically at-risk
      group of children. The relationships between biological and psychosocial
      variables in the first year and school-age asthma support the formulation of
      asthma as beginning early in life, with the developing immune system interacting
      with environmental influences. The data provide support for the possible
      contribution of psychosocial factors to asthma onset and persistence into
      childhood.

PMID- 11581478
TI  - Parallel incidences of sudden infant death syndrome and infantile hypertrophic
      pyloric stenosis: a common cause?
AB  - OBJECTIVE: To determine whether there was a correlation between the incidence of
      infantile hypertrophic pyloric stenosis (IHPS) and the incidence of sudden infant
      death syndrome (SIDS) during the period 1970 to 1997 and to discuss different
      causative factors that could be influencing the changing trend in incidence.
      METHODS: We compared the incidence of IHPS in the Stockholm Health Care Region
      with the incidence of SIDS in Sweden each year between 1970 and 1997. First, the
      relation was assessed by calculation of a correlation coefficient; second, the
      relative linear decrease was estimated for the time period 1990 to 1997. RESULTS:
      The incidence of IHPS increased steadily during the 1970s, from 0.5 per 1000 live
      births in 1970 to 2.7 in 1979. During the 1980s, the average incidence was 2.8.
      During the 1990s, there was a significant decrease in the number of IHPS cases in
      Stockholm. The incidence rate of IHPS parallels the incidence of SIDS during the
      study period (r = 0.58). The incidence of SIDS dropped after the risk-reduction
      campaign in the beginning of the 1990s, which recommended that infants sleep on
      their back. We could not identify any other changes of behavioral risk factors in
      early exposures that could explain the temporal trends. CONCLUSIONS: The
      statistical findings suggest that IHPS and SIDS have causative factors in common.
      We suggest that prone sleeping is one of those factors.

PMID- 11581479
TI  - Effect of a single-use sterile catheter for each void on the frequency of
      bacteriuria in children with neurogenic bladder on intermittent catheterization
      for bladder emptying.
AB  - OBJECTIVE: The frequency of bacteriuria is high in children with neurogenic
      bladder on intermittent catheterization for bladder emptying. In an effort to
      decrease bacteriuria, we examined whether the method of catheter care was
      responsible for the high rate of bacteriuria. For this, the frequency of
      bacteriuria was examined in the same patient on single-use sterile catheters and
      on reused clean catheters. METHODS: A prospective, randomized, crossover trial
      was conducted with 10 patients who were randomized to 4 months of a new, sterile
      catheter for intermittent catheterization and 4 months of reuse of a clean
      catheter for intermittent catheterization. Each week, a urine sample was
      collected and symptoms of infection and medication use were recorded. RESULTS: A
      total of 158 urine samples were collected during 164 patient-weeks on the new
      catheter method for each void; 115 (73%) were positive for a pathogen. Of the 161
      samples collected during 169 patient-weeks on the standard, reuse method for
      voiding, 123 (76%) were positive (115 [73%] of 158 vs 123 [76%] of 161).
      Escherichia coli was the most common pathogen detected during both method
      periods. CONCLUSION: A new, sterile catheter for each void did not decrease the
      high frequency of bacteriuria in patients with neurogenic bladder on intermittent
      catheterization.

PMID- 11581480
TI  - Impact of protease inhibitor-containing combination antiretroviral therapies on
      height and weight growth in HIV-infected children.
AB  - OBJECTIVE: To examine beneficial or detrimental effects of protease inhibitor
      (PI)-containing antiretroviral regimens on height and weight growth in children
      with human immunodeficiency virus (HIV) infection. METHODS: A prospective cohort
      study was conducted of 906 HIV-infected children, from pediatric research clinics
      in the United States, who were between 3 months and 18 years of age and who had
      height and weight assessed in 1995 (before introduction of PIs in this
      population) and at least once more through 1999. Changes in age- and gender
      adjusted height and weight growth associated with PI use were assessed. RESULTS:
      Compared with a healthy reference population, children were more affected in
      height (mean z score: -0.90 [18th percentile]) than in weight (mean z score: 
      0.42 [34th percentile]) at baseline (1995). Two thirds of children received at
      least 1 PI during 1996 to 1999. In the multivariate mixed effects regression
      models adjusted for baseline log(10) CD4 cell count, baseline age, gender, and
      race/ethnicity, the use of PIs was associated with per-year gains of 0.13 z
      scores in height and 0.05 z scores in weight relative to the expected growth with
      non-PI-containing regimens (eg, after 1 year of PI use, a representative 6-year
      old boy in our study would be approximately 0.7 cm taller and 0.1 kg heavier than
      if he had not received PIs). No significant differential effects of PIs on height
      or weight growth according to specific agents or children's sociodemographic or
      clinical characteristics were found. CONCLUSIONS: Although the use of PI
      containing regimens was not associated with growth retardation, it was associated
      with only small annual increments in height and weight growth in HIV-infected
      children.

PMID- 11581481
TI  - Antipyretic efficacy of an initial 30-mg/kg loading dose of acetaminophen versus
      a 15-mg/kg maintenance dose.
AB  - OBJECTIVE: To compare the antipyretic efficacy of an initial 30-mg/kg
      acetaminophen loading dose versus a 15-mg/kg maintenance dose. METHODS: A double
      blind, parallel-group, randomized clinical trial was conducted. A total of 121
      febrile (rectal temperature between 39 degrees C and 40 degrees C) but otherwise
      healthy outpatients who were 4 months to 9 years of age and weighed 4 to 26 kg
      were assigned randomly to 1 of the dose groups: 15 mg/kg (n = 62) and 30 mg/kg (n
      = 59). RESULTS: In an "intention to treat" analysis, the time to obtain a
      temperature lower than 38.5 degrees C was significantly shorter in the 30-mg/kg
      than in the 15-mg/kg group (110 +/- 94 minutes vs 139 +/- 113 minutes). The
      maximum temperature decrease was significantly higher in the 30-mg/kg than in the
      15-mg/kg group (2.3 +/- 0.7 degrees C vs 1.7 +/- 0.6 degrees C). Duration of
      rectal temperature below 38.5 degrees C was significantly longer in the 30-mg/kg
      than in the 15-mg/kg group (250 +/- 92 minutes vs 185 +/- 121 minutes,
      respectively). Adverse events were reported in 6 children in the 30-mg/kg group
      compared with 5 in the 15-mg/kg group (hyperthermia, hypothermia, vomiting). The
      difference was not statistically significant. CONCLUSION: An initial 30-mg/kg
      acetaminophen loading dose seemed to be more effective in reducing fever than a
      15-mg/kg maintenance dose. No difference was observed regarding clinical
      tolerance. These data suggest that acetaminophen treatment of fever may be more
      efficient in an initial loading dose.

PMID- 11581482
TI  - Detection of red reflex asymmetry by pediatric residents using the Bruckner
      reflex versus the MTI photoscreener.
AB  - OBJECTIVE: To compare the ability of pediatric residents to differentiate an
      asymmetric from a symmetric red reflex in patients with anisometropia and
      microstrabismus using the Bruckner reflex and the Medical Technology Innovations
      (MTI) photoscreener. METHODS: A prospective, masked, case-control study was
      performed. Twelve pediatric residents evaluated 10 study patients and 6 control
      subjects in a masked manner in 2 separate sessions, using the Bruckner reflex or
      the MTI photoscreener, evaluating for asymmetric (abnormal) or symmetric (normal)
      red reflexes between the 2 eyes. Each study patient had asymmetric red reflexes
      and the amblyogenic risk factor of anisometropia or microstrabismus. Each control
      subject had symmetric red reflexes. RESULTS: The pediatric residents had a mean
      correct score of 82% (69%-100%) using the MTI photoscreener versus a mean correct
      score of 65% (44%-81%) using the Bruckner reflex (McNemar test: alpha < 0.01).
      The sensitivity of the MTI photoscreener evaluation was 89% in comparison to 61%
      for the Bruckner reflex. The specificities for the MTI photoscreener versus the
      Bruckner reflex were similar at 69% and 71%, respectively. CONCLUSIONS: Pediatric
      residents were better at detecting asymmetric red reflexes in patients with
      anisometropia and microstrabismus when evaluating MTI photoscreener photographs
      than when evaluating the red reflexes by the Bruckner reflex. The MTI
      photoscreener may be a more sensitive method than the Bruckner reflex to screen
      for the common amblyogenic risk factors of anisometropia and microstrabismus by
      easier detection of red reflex asymmetry.

PMID- 11581483
TI  - Development and impact of a computerized pediatric antiinfective decision support
      program.
AB  - OBJECTIVE: Computerized medical decision support tools have been shown to improve
      the quality of care and have been cited by the Institute of Medicine as one
      method to reduce pharmaceutical errors. We evaluated the impact of an
      antiinfective decision support tool in a pediatric intensive care unit (PICU).
      METHODS: We enhanced an existing adult antiinfective management tool by adding
      and changing medical logic to make it appropriate for pediatric patients. Process
      and outcomes measures were monitored prospectively during a 6-month control and a
      6-month intervention period. Mandatory use of the decision support tool was
      initiated for all antiinfective orders in a 26-bed PICU during the intervention
      period. Clinician opinions of the decision support tool were surveyed via
      questionnaire. RESULTS: The rate of pharmacy interventions for erroneous drug
      doses declined by 59%. The rate of anti-infective subtherapeutic patient days
      decreased by 36%, and the rate of excessive-dose days declined by 28%. The number
      of orders placed per antiinfective course decreased 11.5%, and the robust
      estimate of the antiinfective costs per patient decreased 9%. The type of anti
      infectives ordered and the number of antiinfective doses per patient remained
      similar, as did the rates of adverse drug events and antibiotic-bacterial
      susceptibility mismatches. The surveyed clinicians reported that use of the
      program improved their antiinfective agent choices as well as their awareness of
      impairments in renal function and reduced the likelihood of adverse drug events.
      CONCLUSIONS: Use of the pediatric antiinfective decision support tool in a PICU
      was considered beneficial to patient care by the clinicians and reduced the rates
      of erroneous drug orders, improved therapeutic dosage targets, and was associated
      with a decreased robust estimate of antiinfective costs per patient.
      antiinfective agents, decision support systems, drug therapy, medication errors,
      child, infant.

PMID- 11581484
TI  - Infantile scurvy: a historical perspective.
AB  - Scurvy, a disease of dietary deficiency of vitamin C, is uncommon today. Among
      diseases, scurvy has a rich history and an ancient past. The Renaissance (14th to
      16th centuries) witnessed several epidemics of scurvy among sea voyagers. In
      1747, James Lind, a British Naval surgeon, performed a carefully designed
      clinical trial and concluded that oranges and lemons had the most antiscorbutic
      effect. Eventually, with the provision of lemon juice to the sea voyagers, scurvy
      became rare at sea. Infantile scurvy appeared almost as a new disease toward the
      end of the 19th century. The increased incidence of infantile scurvy during that
      period was attributed to the usage of heated milk and proprietary foods. Thomas
      Barlow described the classic clinical and pathologic features of infantile scurvy
      in 1883. Between 1907 and 1912, Holst and Frolich induced and cured scurvy in
      guinea pigs by dietary modification. In 1914, Alfred Hess established that
      pasteurization reduced the antiscorbutic value of milk and recommended
      supplementation of fresh fruit and vegetable juices to prevent scurvy. Such
      pioneering efforts led to the eradication of infantile scurvy in the United
      States. A brief history of infantile scurvy is provided.

PMID- 11581485
TI  - Childhood methanol ingestion treated with fomepizole and hemodialysis.
AB  - Fomepizole (4-methylpyrazole; Antizol) is used increasingly in the treatment of
      methanol toxicity in adults. Little experience exists with this drug in the
      pediatric population, however. We present a case of methanol poisoning in a child
      in whom the use of fomepizole averted intravenous ethanol infusion and the
      attendant side effects of this therapy.

PMID- 11581486
TI  - Sleep disorders.

PMID- 11581487
TI  - Index of suspicion.

PMID- 11581488
TI  - Peptic ulcer disease in children.

PMID- 11581489
TI  - Anaphylactoid reactions to radiocontrast agents.

PMID- 11581490
TI  - What's new: newly approved drugs for children.

PMID- 11581492
TI  - Architecture of the optic chiasm and the mechanisms that sculpt its development.
AB  - At the optic chiasm the two optic nerves fuse, and fibers from each eye cross the
      midline or turn back and remain uncrossed. Having adopted their pathways the
      fibers separate to form the two optic tracts. Research into the architecture and
      development of the chiasm has become an area of increasing interest. Many of its
      mature features are complex and vary between different animal types. It is
      probable that numerous factors sculpt its development. The separate ganglion cell
      classes cross the midline at different locations along the length of the chiasm,
      reflecting their distinct periods of production as the chiasm develops in a caudo
      rostral direction. In some mammals, uncrossed axons are mixed with crossed axons
      in each hemi-chiasm, whereas in others they remain segregated. These
      configurations are the product of different developmental mechanisms. The
      morphology of the chiasm changes significantly during development. Neurons, glia,
      and the signals they produce play a role in pathway selection. In some animals
      fiber-fiber interactions are also critical, but only where crossed and uncrossed
      pathways are mixed in each hemi-chiasm. The importance of the temporal dimension
      in chiasm development is emphasized by the fact that in some animals uncrossed
      ganglion cells are generated abnormally early in relation to their retinal
      location. Furthermore, in albinos, where many cells do not exit the cell cycle at
      normal times, there are systematic chiasmatic abnormalities in ganglion cell
      projections.

PMID- 11581493
TI  - Ion channels and their functional role in vascular endothelium.
AB  - Endothelial cells (EC) form a unique signal-transducing surface in the vascular
      system. The abundance of ion channels in the plasma membrane of these
      nonexcitable cells has raised questions about their functional role. This review
      presents evidence for the involvement of ion channels in endothelial cell
      functions controlled by intracellular Ca(2+) signals, such as the production and
      release of many vasoactive factors, e.g., nitric oxide and PGI(2). In addition,
      ion channels may be involved in the regulation of the traffic of macromolecules
      by endocytosis, transcytosis, the biosynthetic-secretory pathway, and exocytosis,
      e.g., tissue factor pathway inhibitor, von Willebrand factor, and tissue
      plasminogen activator. Ion channels are also involved in controlling
      intercellular permeability, EC proliferation, and angiogenesis. These functions
      are supported or triggered via ion channels, which either provide Ca(2+)-entry
      pathways or stabilize the driving force for Ca(2+) influx through these pathways.
      These Ca(2+)-entry pathways comprise agonist-activated nonselective Ca(2+)
      permeable cation channels, cyclic nucleotide-activated nonselective cation
      channels, and store-operated Ca(2+) channels or capacitative Ca(2+) entry. At
      least some of these channels appear to be expressed by genes of the trp family.
      The driving force for Ca(2+) entry is mainly controlled by large-conductance
      Ca(2+)-dependent BK(Ca) channels (slo), inwardly rectifying K(+) channels
      (Kir2.1), and at least two types of Cl( -) channels, i.e., the Ca(2+)-activated
      Cl(-) channel and the housekeeping, volume-regulated anion channel (VRAC). In
      addition to their essential function in Ca(2+) signaling, VRAC channels are
      multifunctional, operate as a transport pathway for amino acids and organic
      osmolytes, and are possibly involved in endothelial cell proliferation and
      angiogenesis. Finally, we have also highlighted the role of ion channels as
      mechanosensors in EC. Plasmalemmal ion channels may signal rapid changes in
      hemodynamic forces, such as shear stress and biaxial tensile stress, but also
      changes in cell shape and cell volume to the cytoskeleton and the intracellular
      machinery for metabolite traffic and gene expression.

PMID- 11581494
TI  - Heat shock proteins and cardiovascular pathophysiology.
AB  - In the eukaryotic cell an intrinsic mechanism is present providing the ability to
      defend itself against external stressors from various sources. This defense
      mechanism probably evolved from the presence of a group of chaperones, playing a
      crucial role in governing proper protein assembly, folding, and transport.
      Upregulation of the synthesis of a number of these proteins upon environmental
      stress establishes a unique defense system to maintain cellular protein
      homeostasis and to ensure survival of the cell. In the cardiovascular system this
      enhanced protein synthesis leads to a transient but powerful increase in
      tolerance to such endangering situations as ischemia, hypoxia, oxidative injury,
      and endotoxemia. These so-called heat shock proteins interfere with several
      physiological processes within several cell organelles and, for proper
      functioning, are translocated to different compartments following stress-induced
      synthesis. In this review we describe the physiological role of heat shock
      proteins and discuss their protective potential against various stress agents in
      the cardiovascular system.

PMID- 11581495
TI  - Physiological roles and regulation of mammalian sulfate transporters.
AB  - All cells require inorganic sulfate for normal function. Sulfate is among the
      most important macronutrients in cells and is the fourth most abundant anion in
      human plasma (300 microM). Sulfate is the major sulfur source in many organisms,
      and because it is a hydrophilic anion that cannot passively cross the lipid
      bilayer of cell membranes, all cells require a mechanism for sulfate influx and
      efflux to ensure an optimal supply of sulfate in the body. The class of proteins
      involved in moving sulfate into or out of cells is called sulfate transporters.
      To date, numerous sulfate transporters have been identified in tissues and cells
      from many origins. These include the renal sulfate transporters NaSi-1 and sat-1,
      the ubiquitously expressed diastrophic dysplasia sulfate transporter DTDST, the
      intestinal sulfate transporter DRA that is linked to congenital chloride
      diarrhea, and the erythrocyte anion exchanger AE1. These transporters have only
      been isolated in the last 10-15 years, and their physiological roles and
      contributions to body sulfate homeostasis are just now beginning to be
      determined. This review focuses on the structural and functional properties of
      mammalian sulfate transporters and highlights some of regulatory mechanisms that
      control their expression in vivo, under normal physiological and
      pathophysiological states.

PMID- 11581496
TI  - Mechanisms of estrogen action.
AB  - Our appreciation of the physiological functions of estrogens and the mechanisms
      through which estrogens bring about these functions has changed during the past
      decade. Just as transgenic mice were produced in which estrogen receptors had
      been inactivated and we thought that we were about to understand the role of
      estrogen receptors in physiology and pathology, it was found that there was not
      one but two distinct and functional estrogen receptors, now called ER alpha and
      ER beta. Transgenic mice in which each of the receptors or both the receptors are
      inactive have revealed a much broader role for estrogens in the body than was
      previously thought. This decade also saw the description of a male patient who
      had no functional ER alpha and whose continued bone growth clearly revealed an
      important function of estrogen in men. The importance of estrogen in both males
      and females was also demonstrated in the laboratory in transgenic mice in which
      the aromatase gene was inactivated. Finally, crystal structures of the estrogen
      receptors with agonists and antagonists have revealed much about how ligand
      binding influences receptor conformation and how this conformation influences
      interaction of the receptor with coactivators or corepressors and hence
      determines cellular response to ligands.

PMID- 11581497
TI  - Calcium: taste, intake, and appetite.
AB  - This review summarizes research on sensory and behavioral aspects of calcium
      homeostasis. These are fragmented fields, with essentially independent lines of
      research involving gustatory electrophysiology in amphibians, ethological studies
      in wild birds, nutritional studies in poultry, and experimental behavioral
      studies focused primarily on characterizing the specificity of the appetite in
      rats. Recently, investigators have begun to examine potential physiological
      mechanisms underlying calcium intake and appetite. These include changes in the
      taste perception of calcium, signals related to blood calcium concentrations, and
      actions of the primary hormones of calcium homeostasis: parathyroid hormone,
      calcitonin, and 1,25-dihydroxyvitamin D. Other influences on calcium intake
      include reproductive and adrenal hormones and learning. The possibility that a
      calcium appetite exists in humans is discussed. The broad range of observations
      documenting the existence of a behavioral limb of calcium homeostasis provides a
      strong foundation for future genetic and physiological analyses of this behavior.

PMID- 11581498
TI  - The hypothalamus and hypertension.
AB  - Most forms of hypertension are associated with a wide variety of functional
      changes in the hypothalamus. Alterations in the following substances are
      discussed: catecholamines, acetylcholine, angiotensin II, natriuretic peptides,
      vasopressin, nitric oxide, serotonin, GABA, ouabain, neuropeptide Y, opioids,
      bradykinin, thyrotropin-releasing factor, vasoactive intestinal polypeptide,
      tachykinins, histamine, and corticotropin-releasing factor. Functional changes in
      these substances occur throughout the hypothalamus but are particularly prominent
      rostrally; most lead to an increase in sympathetic nervous activity which is
      responsible for the rise in arterial pressure. A few appear to be depressor
      compensatory changes. The majority of the hypothalamic changes begin as the
      pressure rises and are particularly prominent in the young rat; subsequently they
      tend to fluctuate and overall to diminish with age. It is proposed that, with the
      possible exception of the Dahl salt-sensitive rat, the hypothalamic changes
      associated with hypertension are caused by renal and intrathoracic
      cardiopulmonary afferent stimulation. Renal afferent stimulation occurs as a
      result of renal ischemia and trauma as in the reduced renal mass rat. It is
      suggested that afferents from the chest arise, at least in part, from the
      observed increase in left auricular pressure which, it is submitted, is due to
      the associated documented impaired ability to excrete sodium. It is proposed,
      therefore, that the hypothalamic changes in hypertension are a link in an
      integrated compensatory natriuretic response to the kidney's impaired ability to
      excrete sodium.

PMID- 11581499
TI  - Rhodopsin: structural basis of molecular physiology.
AB  - The crystal structure of rod cell visual pigment rhodopsin was recently solved at
      2.8-A resolution. A critical evaluation of a decade of structure-function studies
      is now possible. It is also possible to begin to explain the structural basis for
      several unique physiological properties of the vertebrate visual system,
      including extremely low dark noise levels as well as high gain and color
      detection. The ligand-binding pocket of rhodopsin is remarkably compact, and
      several apparent chromophore-protein interactions were not predicted from
      extensive mutagenesis or spectroscopic studies. The transmembrane helices are
      interrupted or kinked at multiple sites. An extensive network of interhelical
      interactions stabilizes the ground state of the receptor. The helix movement
      model of receptor activation, which might apply to all G protein-coupled
      receptors (GPCRs) of the rhodopsin family, is supported by several structural
      elements that suggest how light-induced conformational changes in the ligand
      binding pocket are transmitted to the cytoplasmic surface. The cytoplasmic domain
      of the receptor is remarkable for a carboxy-terminal helical domain extending
      from the seventh transmembrane segment parallel to the bilayer surface. Thus the
      cytoplasmic surface appears to be approximately the right size to bind to the
      transducin heterotrimer in a one-to-one complex. Future high-resolution
      structural studies of rhodopsin and other GPCRs will form a basis to elucidate
      the detailed molecular mechanism of GPCR-mediated signal transduction.

PMID- 11581500
TI  - The organizing potential of sphingolipids in intracellular membrane transport.
AB  - Eukaryotes are characterized by endomembranes that are connected by vesicular
      transport along secretory and endocytic pathways. The compositional differences
      between the various cellular membranes are maintained by sorting events, and it
      has long been believed that sorting is based solely on protein-protein
      interactions. However, the central sorting station along the secretory pathway is
      the Golgi apparatus, and this is the site of synthesis of the sphingolipids.
      Sphingolipids are essential for eukaryotic life, and this review ascribes the
      sorting power of the Golgi to its capability to act as a distillation apparatus
      for sphingolipids and cholesterol. As Golgi cisternae mature, ongoing
      sphingolipid synthesis attracts endoplasmic reticulum-derived cholesterol and
      drives a fluid-fluid lipid phase separation that segregates sphingolipids and
      sterols from unsaturated glycerolipids into lateral domains. While sphingolipid
      domains move forward, unsaturated glycerolipids are retrieved by recycling
      vesicles budding from the sphingolipid-poor environment. We hypothesize that by
      this mechanism, the composition of the sphingolipid domains, and the surrounding
      membrane changes along the cis-trans axis. At the same time the membrane
      thickens. These features are recognized by a number of membrane proteins that as
      a consequence of partitioning between domain and environment follow the domains
      but can enter recycling vesicles at any stage of the pathway. The interplay
      between protein- and lipid-mediated sorting is discussed.

PMID- 11581501
TI  - Spinal and supraspinal factors in human muscle fatigue.
AB  - Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle
      force. It may arise not only because of peripheral changes at the level of the
      muscle, but also because the central nervous system fails to drive the
      motoneurons adequately. Evidence for "central" fatigue and the neural mechanisms
      underlying it are reviewed, together with its terminology and the methods used to
      reveal it. Much data suggest that voluntary activation of human motoneurons and
      muscle fibers is suboptimal and thus maximal voluntary force is commonly less
      than true maximal force. Hence, maximal voluntary strength can often be below
      true maximal muscle force. The technique of twitch interpolation has helped to
      reveal the changes in drive to motoneurons during fatigue. Voluntary activation
      usually diminishes during maximal voluntary isometric tasks, that is central
      fatigue develops, and motor unit firing rates decline. Transcranial magnetic
      stimulation over the motor cortex during fatiguing exercise has revealed focal
      changes in cortical excitability and inhibitability based on electromyographic
      (EMG) recordings, and a decline in supraspinal "drive" based on force recordings.
      Some of the changes in motor cortical behavior can be dissociated from the
      development of this "supraspinal" fatigue. Central changes also occur at a spinal
      level due to the altered input from muscle spindle, tendon organ, and group III
      and IV muscle afferents innervating the fatiguing muscle. Some intrinsic adaptive
      properties of the motoneurons help to minimize fatigue. A number of other central
      changes occur during fatigue and affect, for example, proprioception, tremor, and
      postural control. Human muscle fatigue does not simply reside in the muscle.

PMID- 11581502
TI  - Electrophysiology of the sodium-potassium-ATPase in cardiac cells.
AB  - Like several other ion transporters, the Na(+)-K(+) pump of animal cells is
      electrogenic. The pump generates the pump current I(p). Under physiological
      conditions, I(p) is an outward current. It can be measured by
      electrophysiological methods. These methods permit the study of characteristics
      of the Na(+)-K(+) pump in its physiological environment, i.e., in the cell
      membrane. The cell membrane, across which a potential gradient exists, separates
      the cytosol and extracellular medium, which have distinctly different ionic
      compositions. The introduction of the patch-clamp techniques and the enzymatic
      isolation of cells have facilitated the investigation of I(p) in single cardiac
      myocytes. This review summarizes and discusses the results obtained from I(p)
      measurements in isolated cardiac cells. These results offer new exciting insights
      into the voltage and ionic dependence of the Na(+)-K(+) pump activity, its effect
      on membrane potential, and its modulation by hormones, transmitters, and drugs.
      They are fundamental for our current understanding of Na(+)-K(+) pumping in
      electrically excitable cells.

PMID- 11581503
TI  - The role of vision in control of orientation in a back tuck somersault.
AB  - During a back tuck somersault, the angular velocity of the head is thought to
      surpass the visual system's ability to maintain a distinct and continuous picture
      of the environment. The primary objectives of this research were to determine if
      differences existed with regard to trunk and lower body kinematics, as well as
      landing balance, when gymnasts perform back tuck somersaults under different
      vision conditions. Ten female gymnasts (age = 11.6 +/- 2.67 years, competitive
      level = 8 +/- 1.15, and training time in gymnastics = 5.9 +/- 1.63 years)
      performed back tuck somersaults under 4 vision conditions while wearing
      electromagnetic sensors that allowed automatic digitizing. Although no
      significant differences were found between vision conditions with regard to
      timing, joint angles, and joint angular velocities, gymnasts were more stable at
      landing under conditions that allowed vision during either the entire somersault
      or the last half of the sumersault.

PMID- 11581504
TI  - Specificity versus variability: effects of practice conditions on the use of
      afferent information for manual aiming.
AB  - Although proponents of the motor schema theory hold that a decrease in the
      reliance on afferent information will occur with practice in consort with the
      development of motor programs, supporters of the specificity of practice by
      hypothesis suggest that a performer's reliance on the available sources of
      afferent information during acquisition increases with the amount of practice. To
      reconcile these competing positions, four groups of 9 participants aimed to
      targets under either a constant or a variable practice schedule, with or without
      vision of the effector. After modest (15 trials) and moderate (150 trials)
      practice, participants were tested in both their own and in the alternate vision
      condition. Results indicate that the utilization of online kinesthetic
      information was enhanced through practice regardless of the availability of
      vision during acquisition. This was especially true for the groups practicing
      under a variable practice schedule

PMID- 11581505
TI  - Stability of bimanual coordination in Parkinson's disease and cognitive
      modulation of intention.
AB  - The functional integrity of the bimanual neuro-motor system of Parkinson's
      disease (PD) subjects (stageII) compared to controls (2 x n = 16) was evaluated
      by measures of coordination stability of tapping in in-phase, anti-phase, and 90
      degrees-phase. Recently, intentional influence was modeled as an additive
      attractor function on the intrinsic dynamics, resulting in predictions tested by
      Scholz and Kelso (1990). In this study, the intentional influence was modulated
      by attaching cognitive meaning to the rhythmical pattern, which was expected to
      enhance the stability of coordination and, if effective, might be profitable to
      PD patients. Half of the PD subjects significantly lacked stability. They were
      less stable than controls, lost coordination at lower frequencies, and needed
      more time to switch between phase patterns. The reduction of stability was
      reflected in the progression of the disease. Cognitive meaning reduced
      variability of the single-hands but not of relative phase, and no effect on
      switching time was found. The results suggest a weaker coupling strength between
      the limbs in PD patients lacking stability.

PMID- 11581506
TI  - In-hospital and long-term outcomes of patients with acute myocardial infarction
      undergoing direct angioplasty during regular and after hours.
AB  - Off-hours presentation resulted in a significant increase in the onset of pain to
      balloon inflation time (approximately 1.3 hours) as well as the emergency room to
      balloon inflation time (approximately 54 minutes). However, this delay to
      reperfusion did not result in a difference in clinical outcomes (in-hospital or
      long-term) in patients undergoing direct percutaneous transluminal coronary
      angioplasty within 12 hours of the onset of acute myocardial infarction.

PMID- 11581507
TI  - How long is too long?

PMID- 11581508
TI  - Coronary angiography using 4 or 6 French diagnostic catheters: a prospective,
      randomized study.
AB  - Diagnostic catheter size has been progressively decreased in order to reduce
      complications (particularly access-site complications) and permit early
      ambulation after coronary angiography. However, excessive down-sizing can result
      in poor catheter conformation and poor imaging quality of coronary angiograms
      (CA). This study randomly compared the accuracy and angiographic quality (QUAL)
      of CA performed with 4 French (Fr) vs. 6 Fr diagnostic catheters. Injections were
      done manually using a low-viscosity, non-heated, low-osmolality contrast media
      (Iomeprol). CAs were performed via the femoral approach using Judkins catheters.
      Handling, torque, selectively and stability were graded from 1 (excellent) to 4
      (unacceptable) by the operator. QUAL was also graded from 1 (unacceptable) to 10
      (excellent) by the operator in all patients and by an independent Core laboratory
      in 50 patients matched for gender and weight. Between January and April 1997, a
      total of 405 consecutive patients were randomized. Mean age was 63.4 +/- 11.1
      years and 79% were male. Clinical characteristics of patients, quality of left
      coronary catheter and cross-over rates (1.5% with 6 Fr vs. 3.9% with 4 Fr
      catheters) were similar in both groups. Using the right coronary catheters, the
      only difference was handling, which was found to be easier with 6 Fr catheters
      (1.16 +/- 0.55 vs. 1.34 +/- 0.77, respectively; p = 0.007). Similarly, handling
      difficulty using the pigtail catheter was the only significant difference between
      the two groups (1.16 +/- 0.50 vs. 1.33 +/- 0.77, respectively; p = 0.009), but no
      cross-over was necessary in either group. The QUAL of CA was slightly but
      significantly better with 6 Fr than with 4 Fr catheters but considered non
      diagnostic (< 7/10) in 1.4% vs. 6.8% of left CAs (p = NS). Procedural time (21.0
      +/- 7.2 minutes vs. 19.0 +/- 8.1 minutes; p = 0.007) was shorter with 4 Fr
      catheters, but x-ray exposure, compression times and amount of contrast media
      used were similar. Ambulation was obtained at 2 hours in 15.1% vs. 34.0% of
      patients (p < 0.001) and at 4 hours in 43.8% vs. 52.4% (p < 0.05), respectively.
      The incidence of the worst access-site complication (moderate hematoma) was
      similar (1%) in both groups. CA can be performed using 4 Fr catheters and manual
      injections of low-viscosity contrast media with acceptable angiographic results
      in the majority of cases. This is associated with a shorter procedural time and
      earlier ambulation, and a decreased but acceptable angiographic quality.

PMID- 11581509
TI  - Going small -- use of four French catheters for diagnostic angiography.

PMID- 11581510
TI  - "Side balloon stenting": a novel technique for bifurcation lesions.
AB  - We describe a new technique to treat stenoses of coronary bifurcations. The aim
      of this technique, called "side balloon stenting," is to treat the bifurcation
      lesions with the kissing balloon technique, implanting one or more stents without
      removing the guidewires which remain in place during the whole procedure,
      avoiding potential problems of access to the vessels jailed by stent struts. In
      addition, implanting the stent using the kissing balloon technique would prevent
      the "snow-plow" phenomenon (plaque shifting) in the side branch. The "side
      balloon stenting" technique was applied in 29 cases at various levels of coronary
      artery segments involving bifurcations (Table 1). The technical success rate of
      the side balloon stenting was 90% (25 procedures). The elective placement of one
      stent in the main vessel was done in 20/25 procedures (80%), and in only 5/25
      (20%), it was also necessary to insert a second one in the side branch (due to
      suboptimal results), using the "culotte" technique in two and the T-technique in
      the other three. We were unable to advance the system to the right position in 4
      patients (13%): in 2 due to twisting of the guidewires and in the other due to
      vessel tortuosity and insufficient backup of the system (guiding catheter and
      guidewires). In these four last cases, the delivery system was retrieved and a
      stent was successfully implanted in the right position in the main branch.
      Angiographic success (residual stenoses < 30% and TIMI 3 flow in both branches)
      was obtained in 100% of the cases. The post-intervention period was uneventful.
      These preliminary results show that the side balloon stenting technique is both
      feasible and safe in th treatment of coronary bifurcations with a satisfactory
      rate of procedural success and often (82%) positioning only one stent in the
      parent vessel, thus avoiding stenting the side branch. It will be necessary,
      however, to assess, based mainly on restenosis rate, whether these promising
      immediate results will persist in the long run.

PMID- 11581511
TI  - Predictors of mortality at 30 days in high-risk patients treated with direct or
      rescue stenting for acute myocardial infarction: a single center experience.
AB  - BACKGROUND: Coronary stenting in acute myocardial infarction (AMI) is associated
      with a very low adverse event rate when performed at selected centers in clinical
      trials. However, because of exclusion criteria, a low-risk population is usually
      selected, while potential benefits of stenting should be investigated in an
      unselected population, including a larger proportion of high-risk patients.
      METHODS: We analyzed results obtained in 120 consecutive high-risk patients (mean
      age, 64 years; range, 38-95 years; 76% male), so defined according to the
      presence of 1 of the following: age > 75 years; Killip class 3; cardiogenic
      shock; 3-vessel or left main disease; ejection fraction < 45%; anterior AMI;
      previous bypass surgery; and/or out-of-hospital cardiac arrest. A primary
      procedure was performed in 63 patients and a rescue procedure in 57 patients.
      Stenting was attempted in all patients in which coronary occlusion could be
      crossed with the guidewire (117/120) and was successful in 115/117 (98%).
      RESULTS: Procedural success (TIMI 3 flow and residual stenosis < 20%) was
      obtained in 105 patients (88%), while a suboptimal result (TIMI 2 flow) was
      achieved in 9 patients (8%). At 30 days, twenty patients had died (17%
      mortality). For patients non in cardiogenic shock, 30-day mortality was 3.2%. At
      multivariate analysis, cardiogenic shock (p < 0.0001), peak CK-MB mass (p =
      0.01), and suboptimal result (p = 0.018) were significant independent predictors
      of 30-day mortality. Rescue procedures were associated with a significant
      protective effect with respect to mortality (p = 0.033). CONCLUSION: In our
      series, high-risk patients treated with percutaneous intervention for AMI had a
      very high mortality rate in the presence of cardiogenic shock, despite the use of
      stents, intra-aortic balloon pumping and abciximab. In the remaining patients,
      acceptable results were obtained even in the presence of 1 or more risk factors.
      Rescue stenting does not seem to be associated with increased risk compared to
      primary stenting.

PMID- 11581512
TI  - Stenting of the septal perforator coronary artery.
AB  - This report describes the first application of intracoronary stenting to the
      septal perforator coronary artery in a patient with a totally occluded left
      anterior descending coronary artery (LAD) and a patent venous graft to the distal
      LAD. The procedure was successful and resulted in almost complete relief of class
      III angina. Therefore, diseased large septal perforators may cause angina and be
      treated effectively by intracoronary stenting in selected cases.

PMID- 11581513
TI  - Compression of a subintimal or false lumen stent by stenting in the true lumen.
AB  - Subintimal or false lumen deployment is a rare complication of coronary stenting.
      The authors present a case of false lumen right coronary artery stenting with
      subsequent closure of the false lumen followed by stenting of the true lumen and
      compression of the false lumen stent.

PMID- 11581515
TI  - Congenital coarctation and Takayasu's arteritis: aortic stenting employing
      intravascular ultrasound.

PMID- 11581514
TI  - Rotational atherectomy of a stent-jailed septal perforator: a good verdict for
      the prisoner.
AB  - A 61-year-old man is described, in whom percutaneous coronary intervention was
      done to treat critical ostial stenosis of the first and second septal
      perforators. The first branch originated from the stented portion of a previously
      treated left anterior descending artery, while the second branch was distal to
      the stent. During balloon angioplasty, the balloon catheter could not be
      delivered to the lesion site in the first branch, although the second branch was
      easily amenable to balloon dilatation. Rotational atherectomy was done to treat
      the former. Besides advocating rotational atherectomy as a novel strategy for
      managing jailed septal perforators, the case presents an insight into the vastly
      differing interventional situations of stent-jailed branch vis-a-vis de novo
      branch ostial stenosis.

PMID- 11581516
TI  - False aneurysm and mediastinal hematoma: complications of simultaneous
      transcatheter therapy for coarctation of the aorta and patent ductus arteriosus
      in an infant.
AB  - We report an infant with intractable congestive heart failure caused by
      coarctation of the aorta, patent ductus arteriosus, atrial septal defect, and
      multiple muscular ventricular septal defects. He had received balloon angioplasty
      for dilating the aortic coarctation and a Gianturco coil for closing the ductus
      at a single therapeutic catheterization session at 4 months old. After balloon
      angioplasty, his heart failure had dramatically resolved. A false aneurysm and
      mediastinal hematoma were noted on the following day. The hematoma revealed total
      resolution 10 weeks later. He was asymptomatic throughout 12 months of follow-up.

PMID- 11581517
TI  - The role of embolization therapy in the treatment of congenital heart disease.
AB  - Embolization therapy plays a significant role in the treatment and palliation of
      congenital heart disease. Currently, there are several devices available to
      occlude these superfluous vascular connections. This article reviews the
      indications, results and the current technology available for transcatheter
      embolization of vessels.

PMID- 11581518
TI  - How poor writing and bad word choices can turn readers off!: a 'mea culpa'.

PMID- 11581519
TI  - Mechanistic considerations in small fish carcinogenicity testing.
AB  - Historically, small fish species have proven useful both as environmental
      sentinels and as versatile test animals in toxicity and carcinogenicity
      bioassays. They can be bred in large numbers, have low maintenance and bioassay
      costs, and have a low background incidence of tumors. However, more mechanistic
      information is needed to help validate the information garnered from these models
      and to keep pace with other more fully developed animal models. This paper
      focuses on mechanistic considerations when using small fish models for
      carcinogenicity testing. Several small aquarium fish species have proven useful.
      The Japanese medaka is perhaps the best characterized small fish model for
      carcinogenicity testing; however, the zebrafish is emerging as an important model
      because it is well characterized genetically. Both route and methodology of
      exposure may affect the outcome of the study. Most studies have been conducted by
      introducing the test compound into the ambient water, but dietary exposures and
      embryo microinjection have also been used. Other considerations in study design
      include use of an initiating carcinogen, such as diethlynitrosamine, and
      differences in xenobiotic metabolism, such as the fact that fish CYP2B is
      refractory to phenobarbital induction. The small size of these models has perhaps
      limited some types of mechanistic studies, such as formation and repair of DNA
      adducts in response to carcinogen exposure. However, improved analytical methods
      are allowing greater resolution and should be applied to small fish species.
      Slide-based methods such as immunohistochemistry are an important adjunct to
      routine histopathology and should be included in study design. However, there is
      a need for development of more species-specific antibodies for fish research.
      There is also a need for more fish-specific data on cytokines, serum
      biochemistry, and oncogenes to strengthen the use of these important test models.

PMID- 11581520
TI  - A fish model of renal regeneration and development.
AB  - The fish kidney provides a unique model for investigating renal injury, repair,
      and development. Like mammalian kidneys, fish kidneys have the remarkable ability
      to repair injured nephrons, designated renal regeneration. This response is
      marked by a recovery from acute renal failure by replacing the injured cells with
      new epithelial cells, restoring tubule integrity. In addition, fish have the
      ability to respond to renal injury by de novo nephron neogenesis. This response
      occurs in multiple fish species including goldfish, zebrafish, catfish, trout,
      tilapia, and the aglomerular toadfish. New nephrons develop in the weeks after
      the initial injury. This nephrogenic response can be induced in adult fish,
      providing a more abundant source of developing renal tissue compared with fetal
      mammalian kidneys. Investigating the roles played by different parts of the
      nephron during development and repair can be facilitated using fish models with
      differing renal anatomy, such as aglomerular fish. The fish nephron neogenesis
      model may also help to identify novel genes involved in nephrogenesis,
      information that could eventually be used to develop alternative renal
      replacement therapies.

PMID- 11581521
TI  - Development of sensory systems in zebrafish (Danio rerio).
AB  - Zebrafish possess all of the classic sensory modalities: taste, tactile, smell,
      balance, vision, and hearing. For each sensory system, this article provides a
      brief overview of the system in the adult zebrafish followed by a more detailed
      overview of the development of the system. By far the majority of studies
      performed in each of the sensory systems of the zebrafish have involved some
      aspect of molecular biology or genetics. Although molecular biology and genetics
      are not major foci of the paper, brief discussions of some of the mutant strains
      of zebrafish that have developmental defects in each specific sensory system are
      included. The development of the sensory systems is only a small sampling of the
      work being done using zebrafish and provides a mere glimpse of the potential of
      this model for the study of vertebrate development, physiology, and human
      disease.

PMID- 11581522
TI  - Xiphophorus interspecies hybrids as genetic models of induced neoplasia.
AB  - Fishes of the genus Xiphophorus (platyfishes and swordtails) are small,
      internally fertilizing, livebearing, and derived from freshwater habitats in
      Mexico, Guatemala, Belize, and Honduras. Scientists have used these fishes in
      cancer research studies for more than 70 yr. The genus is presently composed of
      22 species that are quite divergent in their external morphology. Most cancer
      studies using Xiphophorus use hybrids, which can be easily produced by artificial
      insemination. Phenotypic traits, such as macromelanophore pigment patterns, are
      often drastically altered as a result of lack of gene regulation within hybrid
      fishes. These fish can develop large exophytic melanomas as a result of
      upregulated expression of these pigment patterns. Because backcross hybrid fish
      are susceptible to the development of melanoma and other neoplasms, they can be
      subjected to potentially deleterious chemical and physical agents. It is thus
      possible to use gene mapping and cloning methodologies to identify and
      characterize oncogenes and tumor suppressors implicated in spontaneous or induced
      neoplasia. This article reviews the history of cancer research using Xiphophorus
      and recent developments regarding DNA repair capabilities, mapping, and cloning
      of candidate genes involved in neoplastic phenotypes. The particular genetic
      complexity of melanoma in these fishes is analyzed and reviewed.

PMID- 11581523
TI  - Trangenic fish as models in environmental toxicology.
AB  - Historically, fish have played significant roles in assessing potential risks
      associated with exposure to chemical contamination in aquatic environments.
      Considering the contributions of transgenic rodent models to biomedicine, it is
      reasoned that the development of transgenic fish could enhance the role of fish
      in environmental toxicology. Application of transgenic fish in environmental
      studies remains at an early stage, but recent introduction of new models and
      methods demonstrates progress. Rapid advances are most evident in the area of in
      vivo mutagenesis using fish carrying transgenes that serve as recoverable
      mutational targets. These models highlight many advantages afforded by fish as
      models and illustrate important issues that apply broadly to transgenic fish in
      environmental toxicology. Development of fish models carrying identical
      transgenes to those found in rodents is beneficial and has revealed that numerous
      aspects of in vivo mutagenesis are similar between the two classes of
      vertebrates. Researchers have revealed that fish exhibit frequencies of
      spontaneous mutations similar to rodents and respond to mutagen exposure
      consistent with known mutagenic mechanisms. Results have demonstrated the
      feasibility of in vivo mutation analyses using transgenic fish and have
      illustrated their potential value as a comparative animal model. Challenges to
      development and application of transgenic fish relate to the needs for improved
      efficiencies in transgenic technology and in aspects of fish husbandry and use.
      By taking advantage of the valuable and unique attributes of fish as test
      organisms, it is anticipated that transgenic fish will make significant
      contributions to studies of environmentally induced diseases.

PMID- 11581524
TI  - Progressive Supranuclear Palsy.
AB  - Unfortunately, no drug treatment has been shown to benefit patients with
      progressive supranuclear palsy (PSP) more than modestly or briefly. The
      multiplicity of neuronal systems and synaptic physiologies that degenerate in
      this disorder makes a neurotransmitter-specific approach, such as
      neurotransmitter replacement or reuptake inhibition, unlikely to succeed.
      Nevertheless, some of these are worth trying in nearly every patient with PSP.
      Useful drug treatment may ultimately take the form of enhancers of mitochondrial
      energy metabolism, inducers of endogenous neurotrophic factors, and, even further
      in the future, inhibitors of tau aggregation or regulators of alternative
      splicing. The neurologist familiar with PSP can assist patients and their family
      by providing prognostic information, by avoiding unnecessary diagnostic tests,
      and by prescribing measures to minimize aspiration and falling, the two most
      dangerous complications of PSP.

PMID- 11581525
TI  - Parkinson's Disease: Initial Treatment with Levodopa or Dopamine Agonists.
AB  - The question of whether to use levodopa (LD) or dopamine agonists as initial
      therapy in Parkinson's disease has been a controversy for nearly 20 years. There
      are several issues relating to this treatment regimen that may effect ones
      decision. Review of them results in the following conclusions: LD does not cause
      the onset of motor fluctuations and dyskinesia; it probably relates to disease
      progression. Tolerance does not develop with long-term LD therapy. LD is not
      toxic. LD decreases mortality in Parkinson's disease. Motor fluctuations can
      occur with dopamine-agonist monotherapy, but the actual frequency is as yet
      unknown. Dopamine agonists are not neuroprotective. Clinical trials have
      indicated that LD remains the most potent symptomatic therapeutic agent
      available. Dopamine agonists do provide some symptomatic relief when used alone
      in early Parkinson's disease. Standard preparations of LD have the same effect on
      early disease as controlled release preparations. Dopamine agonists cause less
      dyskinesia and fluctuations. These conclusions indicate that both drugs are
      effective symptomatic agents with their own positive and negative aspects. There
      is no incorrect choice. It is reasonable to start young onset patients (younger
      than 50 years of age) with an agonist, because they seem to be more prone to
      develop motor fluctuations and dyskinesia. However, if employment is in jeopardy
      then LD may be needed. Because agonists cause more hallucinations, freezing, and
      somnolence, problems of particular relevance to the elderly (older than 70
      years), then LD would be the best agent for older onset patients. In general, but
      particularly for those falling in between these age groups, treatment should be
      individualized. In this time of cost effectiveness, LD remains the least
      expensive of these agents.

PMID- 11581526
TI  - Long-term Medical Treatment for Parkinson's Disease.
AB  - The authors of this paper view Parkinson's disease (PD) as a clinically defined
      progressive syndrome of resting limb tremor, bradykinesia, muscle rigidity, and a
      shuffling unsteady gait that responds well to dopaminergic medications.
      Parkinson's disease is a not a single entity, but rather a syndrome with diverse
      causes, with both genetic and environmental risk factors. The clinician's concern
      is to rule out other entities, especially those having another specific
      treatment, and to give PD patients the best short- and long-term benefit, with
      the least possible unwanted side effects.

PMID- 11581528
TI  - Paroxysmal Dyskinesia.
AB  - This group of disorders is characterized by periodic sudden events of involuntary
      movement. The clinical range of these involuntary movements is wide including
      tonic spasms, choreiform and athetoid movements and sustained dystonic postures.
      Confusion with reflex forms of epilepsy has been common in the past, but in
      general, paroxysmal dyskinesias are not associated with alterations in
      consciousness or epileptiform activity on electroencephalogram. The underlying
      basis of the paroxysmal dyskinesia is under active investigation as is their
      relationship to epilepsy and other paroxysmal disorders.

PMID- 11581527
TI  - Diffuse Lewy Body Disease.
AB  - Diffuse Lewy body disease (DLB) is a neurodegenerative disorder characterized by
      dementia, fluctuations in mental status, hallucinations, and parkinsonism.
      Diffuse Lewy body disease is the second most common cause of dementia, following
      Alzheimer's disease. The treatment of DLB includes cholinergic therapy for
      cognitive impairment, atypical neuroleptics to alleviate hallucinations, and
      levodopa/carbidopa to improve parkinsonism. The recognition and diagnosis of DLB
      has critical treatment implications. Centrally acting cholinesterase inhibitors,
      such as rivastigmine, donepezil, and galantamine partially reverse decreased
      cortical cholinergic activity and may improve cognition and neuropsychiatric
      symptoms in DLB. Rivastigmine has been demonstrated to improve cognition and
      neuropsychiatric symptoms in patients with DLB without worsening parkinsonian
      features. Due to the potential adverse events associated with neuroleptics in
      this population, treatment with cholinesterase inhibitors is currently considered
      first-line therapy in the treatment of hallucinations and mental status
      fluctuations in DLB. Exquisite sensitivity to neuroleptic medications is a
      hallmark of DLB and life-threatening complications have been reported. Caution
      should be exercised when implementing antipsychotic therapy for the treatment of
      behavioral disturbances of DLB. When required, atypical neuroleptics with the
      least extrapyramdial side effects, such as quetiapine, should be used. The
      parkinsonian features of DLB may respond to dopaminergic therapy with levodopa.
      If parkinsonian symptoms result in clinical disability, a trial of levodopa is
      warranted. Unfortunately, dopaminergic medications may worsen hallucinations.
      Because dopamine agonists have a greater tendency to induce hallucinations and
      somnolence, levodopa is the treatment of choice for parkinsonism in DLB. Rapid
      eye movement (REM) sleep behavior disorder (RBD) is now recognized as a feature
      of DLB. Awareness of the presence of this symptom in patients with DLB is
      important and treatment with low dose clonazepam may help. Cholinergic
      aumentation may also improve these symptoms in patients with DLB.

PMID- 11581529
TI  - Neurosarcoidosis.
AB  - Neurosarcoidosis is an uncommon disorder and requires a careful clinical
      evaluation to reach a diagnosis. Generally, patients with peripheral symptoms,
      which include paresthesias, painful patches over extremities, and stocking glove
      deficits, have a better outcome when compared with those with central nervous
      system (CNS) involvement. Patients with mass lesions or hydrocephalus tend to
      have more relapses and are often more resistant to routine therapy.
      Neurosarcoidosis often responds to glucocorticoids, usually within days or weeks
      of initiating therapy. Patients are usually maintained on 40 to 80 mg per day for
      4 to 6 weeks, then tapered slowly. The use of alternative treatments for
      refractory neurosarcoidosis, or to reduce or eliminate steroids, includes
      methotrexate, cyclophosphamide, azathioprine, cyclosporine, chlorambucil,
      chloroquine, and hydroxychloroquine.

PMID- 11581530
TI  - Acute Disseminated Encephalomyelitis.
AB  - There is no standard therapy for acute disseminated encephalomyelitis (ADEM), and
      treatments are based on the analogy of the pathogenesis of ADEM with that of
      multiple sclerosis (MS), namely an inflammatory perivenular demyelination. High
      dose intravenous corticosteroids, such as methylprednisolone, at a dosage
      standard for MS relapses have been commonly used. Plasmapheresis, beginning with
      a course of four to six plasma exchanges, has also been used, particularly when
      intravenous methylprednisolone has failed. Intravenous immunoglobulin is a third
      potential therapeutic modality.

PMID- 11581531
TI  - Neurologic Complications of Organ Transplantation.
AB  - Over the past four decades, remarkable advances have been made in the field of
      organ transplantation. Improved surgical techniques and perioperative care have
      reduced the mortality and morbidity of many organ transplant procedures to
      acceptable levels. The creation of national and international organ registries
      has resulted in a more efficient system for organ procurement and use. Advances
      in immunology and the introduction of more potent immunomodulating agents have
      led to doubling of survival rates for those with transplanted grafts.
      Unfortunately, a high rate of neurologic complications associated with organ
      transplantation persists. Cerebral embolization, hypoxia, and bleeding remain
      frequent after heart and lung transplantation. Prolonged thrombocytopenia
      associated with bone marrow transplantation still leads to catastrophic cerebral
      hemorrhage. Although the period of neutropenia following bone marrow
      transplantation has been reduced by the use of growth factors, and the routine
      use of potent prophylactic antibiotic and antiviral agents has reduced the
      incidence of infection, unusual or resistant central nervous system (CNS)
      infections continues to arise, often creating difficult treatment choices.
      Furthermore, the more effective classes of immunosuppressants may have direct
      toxic effects on the nervous system. The major challenge for the future is to
      develop agents and strategies for management that can effect selective tolerance
      to the donated organ without paralyzing the immune system's ability to fight
      infection. Such agents must also have limited or no toxicity to the nervous and
      other organ systems. The observations by Starzl on the existence of leukocyte
      chimerism years after transplantation suggest that understanding and building on
      this natural phenomenon may hold promise for solving major problems in the field
      of organ transplantation.

PMID- 11581532
TI  - Rasmussen's Encephalitis.
AB  - When the diagnosis of Rasmussen's encephalitis is being considered, it is
      important to rapidly exclude other causes of epilepsia partialis continua and
      hemiparesis. Although there is no good data from randomized trials of different
      immune-related therapies, treatment with immunoglobulin G (IgG), steroids, or
      plasmapheresis is advocated as first-line therapy. It is not unreasonable to
      institute at least two treatment options (eg, IgG followed by plasmapheresis) if
      response to the first treatment is poor. Functional hemispherectomy and its
      variants are associated with a lower long-term complication rate.

PMID- 11581533
TI  - Noninvasive tests of myocardial perfusion: stress tests and their values.

PMID- 11581534
TI  - Tests of myocardial function: echocardiography and nuclear medicine studies.

PMID- 11581535
TI  - Anesthetic considerations in patients with cardiac arrhythmias, pacemakers, and
      AICDs.

PMID- 11581536
TI  - Anesthesia for adult patients with congenital heart disease undergoing noncardiac
      surgery.

PMID- 11581537
TI  - The future of the preoperative clinic?

PMID- 11581538
TI  - Critical review of the ACC/AHA algorithm for stratifying cardiac patients for
      noncardiac surgery.

PMID- 11581539
TI  - Perioperative beta-blockade to reduce cardiac morbidity in noncardiac surgery.

PMID- 11581542
TI  - Muscle strength and fatigue during isokinetic exercise in individuals with
      multiple sclerosis.
AB  - PURPOSE: To compare muscle strength and muscle fatigue of the knee extensors and
      flexors in individuals with multiple sclerosis (MS) and non-MS control subjects
      and to evaluate the reliability of muscle strength and muscle fatigue testing in
      these individuals. METHODS: Thirty individuals (13 women and 2 men for both MS
      and control groups), age (mean +/- SD) 38.8 +/- 10 for MS and 33.1 +/- 7.6 yr for
      controls, participated in this investigation. Peak torque was measured on two
      occasions separated by approximately 7 d at 30, 60, 90, 120, 180 degrees.s(-1)
      with 2 min of recovery between each bout. The nondominant leg was tested followed
      by the dominant leg after 10 min of recovery. Subjects then performed three bouts
      of 30 flexions and extensions of the dominant leg at 180 degrees.s(-1) with 1 min
      of recovery between bouts. RESULTS: The reliability of muscle torque was very
      high for individuals with MS (only 1 of 20 measurements with an ICC below 0.900).
      Total work was also highly reliable for MS, but the Fatigue Index (work during
      the last 15 contractions/work during the first 15 contractions) x 100 was not.
      Peak torque adjusted for age, body mass, and fat free mass (measured by whole
      body plethysmography; the Bod Pod; Life Measurement Instruments; Concord, CA) was
      significantly greater for controls than for MS for three of four lower body
      muscle groups tested. For the muscle fatigue test (3 bouts of 30 knee extensions
      and flexions at 180 degrees.s(-1)), the Fatigue Index was greater (less fatigue)
      for the knee extensors for controls than MS for the third bout. For flexion, the
      Fatigue Index was greater for controls than MS over the three bouts (group
      effect). Total work was significantly greater for controls than MS for the
      flexors (group effect) and approached significance for the extensors.
      CONCLUSIONS: Individuals with MS were weaker than controls when data were
      adjusted for age, body mass, and fat free mass. This latter finding (force
      relative to age and fat free mass) suggests that there is a reduced ability to
      activate muscle mass in MS and/or the muscle mass of individuals with MS is of
      lower quality (i.e., reduced force/unit muscle mass) than controls.

PMID- 11581543
TI  - Fluid intelligence in an older COPD sample after short- or long-term exercise.
AB  - PURPOSE: Research supports an association between aerobic fitness and cognitive
      functioning in chronic obstructive pulmonary disease (COPD) patients. However,
      the impact of exercise intervention duration has not been satisfactorily
      examined. Therefore, the purpose of this study was to examine the effects of a 3
      month and an 18-month exercise intervention on the cognitive functioning of an
      older COPD sample. METHODS: COPD patients (56-80 yr) were given a 3-month
      exercise program and then were randomly assigned to continue for an additional 15
      months (long-term group) or to leave the exercise program (short-term group). Age
      and education were assessed before involvement in the exercise intervention
      (baseline). Fluid intelligence, pulmonary function, aerobic fitness, and
      depression were assessed at baseline, at 3 months, and at 18 months. RESULTS:
      After 3 months of exercise, results indicated that cognitive function and walk
      distance improved significantly. Results also indicated that the gain in
      cognitive function was reliably predicted by the decrease in VE at VO2peak. At 18
      months, results indicated that cognitive performance did not differ between the
      short- and long-term exercise groups, but that walk distance improved
      significantly for the long-term group, but not for the short-term group. Results
      of a regression analysis showed that the cognitive performance improvement from 3
      months to 18 months was predicted by the gain in walk distance and by the
      decrease in VE at VO2peak. CONCLUSION: It is concluded that improvements in
      aerobic fitness are associated with gains in fluid intelligence after 3 and 18
      months of exercise training in COPD patients. However, at 18 months, exercise
      group was not predictive of the gains in cognitive performance. Therefore, a 3
      month exercise program may be a sufficient impetus to foster these cognitive
      gains in COPD patients.

PMID- 11581544
TI  - A primary care walking exercise program for patients with intermittent
      claudication.
AB  - PURPOSE: In a pilot study, the hypothesis was tested that a home-based walking
      exercise program with structured coaching would improve walking performance and
      adherence in patients with intermittent claudication (IC). METHODS: Thirty-one IC
      patients with a rest ankle-brachial pressure index < 0.90 started a 24-wk walking
      program in the home environment. They were coached according to the Health
      Counseling Model (HCM). Patients were instructed to walk at least 9 bouts.wk-1
      and to walk through the pain. The main effect measures were pain-free (initial
      claudication distance (ICD)) and maximum walking distance (absolute claudication
      distance (ACD)) measured with a graded treadmill test, a corridor exercise test,
      a walking-diary, and the score on the Walking Impairment Questionnaire (WIQ).
      RESULTS: Twenty-four participants completed the program. The reported walking
      frequency was 7.4 times.wk-1. The average ICD improved from 289 m (95% CI, 209
      369) to 347 m (95% CI, 244-449) (P < 0.05) and from 241 m (95% CI, 171-310) to
      373 m (95% CI, 273-472) on the treadmill and the corridor test, respectively. The
      average ACD improved from 490 m (95% CI, 397-583) to 544 m (95% CI, 438-650) and
      from 564 m (95% CI, 412-717) to 726 m (95% CI, 546-906) (P < 0.01) on the
      treadmill and the corridor test, respectively. The average maximum distance
      reported in the walking-diary improved from 957 m (95% CI, 291-1623) to 1294 m
      (95% CI, 646-1941). The score of the walking distance on the WIQ improved from
      57% (95% CI, 42-71%) to 60% (95% CI, 46-74%). CONCLUSION: IC patients improved
      their average ICD and ACD. The walking exercise program in the home environment
      with coaching according to the HCM seems a promising intervention to be tested in
      a randomized controlled trial.

PMID- 11581545
TI  - Effects of exercise and weight loss on blood pressure during daily life.
AB  - PURPOSE: The objective of this study was to investigate the effects of exercise
      training and weight loss on blood pressure (BP) associated with physical activity
      and emotional stress during daily life. METHODS: One hundred twelve participants
      with unmedicated high normal or stage 1 to stage 2 hypertension were randomized
      to one of three conditions: a combined exercise and behavioral weight management
      group (WM), an exercise-only group (EX), or a wait list control group (CON). BP
      was assessed in the clinic and during 15 h of daytime ambulatory BP monitoring at
      baseline and after 6 months of treatment. RESULTS: Increased levels of physical
      activity and emotional distress measured during daily life were associated with
      increases in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart
      rate (HR), and rate pressure product (RPP). After treatment, the WM group had
      significantly lower DBP, HR, and RPP responses during both high and low levels of
      physical activity and emotional distress compared with the CON group. The EX
      group had similar BP levels as the WM group, although the EX group had
      significantly lower BP than the CON group during low but not high levels of
      physical activity and emotional distress. CONCLUSION: These findings indicate
      that exercise, especially when combined with weight loss, reduces BP levels at
      rest and in situations that typically elevate BP such as intense physical
      activity and emotional distress.

PMID- 11581546
TI  - Exercise-induced bronchospasm prevalence in collegiate cross-country runners.
AB  - PURPOSE: The purpose of this study was to determine the prevalence of exercise
      induced bronchospasm (EIB) in collegiate cross-country runners using a protocol
      involving an intense exercise challenge conducted in the same environment in
      which the athletes train and compete. METHODS: One-hundred eighteen collegiate
      cross-country runners from the Los Angeles, California, metropolitan area
      participated in the study. All testing took place on a track at the time and
      location of a normal practice session. The baseline peak expiratory flow rate
      (PEFR) measurements (best of three) and preexercise heart rate were recorded,
      after which the athletes ran 2000 m on a track at 85% of maximum heart rate. The
      postexercise heart rate was recorded and then PEFR measurements at 2, 5, 10, and
      30 min after exercise were recorded. The athletes completed a 16-item
      questionnaire regarding asthma symptoms and health history. Those athletes with a
      history of asthma and currently taking medications for the asthma were then
      excluded from statistical analysis of the questionnaire responses. A decrease in
      PEFR of 15% was considered positive for EIB. RESULTS: Of the 114 athletes not
      currently taking medications for asthma, at least 14% (16 athletes) were EIB
      positive. There was a poor correlation between reported symptoms of asthma and
      testing positive for EIB. CONCLUSION: This study demonstrates a high prevalence
      of EIB in collegiate cross-country runners (at least 14%) and that reported
      symptoms are a poor predictor of actual EIB.

PMID- 11581547
TI  - Abdominal muscle activation of elite male golfers with chronic low back pain.
AB  - PURPOSE: The purpose of this study was twofold: 1) to determine whether elite
      male golfers with chronic low back pain (CLBP) exhibit different abdominal muscle
      activity patterns during the golf swing than asymptomatic control (AC) golfers
      and 2) to determine whether elite male golfers with CLBP experience greater
      fatigue in the abdominal muscles than AC golfers after a typical practice
      session. METHODS: Surface EMG data were collected bilaterally from the rectus
      abdominis (RA), external oblique (EO), and internal oblique (IO) muscles. Muscle
      activity during the golf swing was measured using the root mean square (RMS) of
      the EMG signal in various phases of the golf swing. Fatigue was assessed using
      the median frequency (MF) and RMS of the EMG signal during a 10-s submaximal
      isometric contraction. Low back pain was quantified with the McGill Pain
      Questionnaire before and after the practice session. RESULTS: No differences in
      the RMS of abdominal muscle activity were noted during the golf swing between AC
      and CLBP subjects. However, EO (lead) onset times were significantly delayed with
      respect to the start of the backswing in CLBP subjects. Low back pain in CLBP
      golfers increased significantly after the practice session. Abdominal muscle
      fatigue, as measured with MF or RMS, was not evident after the practice session
      for either AC or CLBP subjects. CONCLUSION: Abdominal muscle activity and muscle
      fatigue characteristics were quite similar between AC and CLBP subjects after
      repetitive golf swings. Despite this, it was clear that repetitive golf swings
      were aggravating some part of the musculoskeletal system in CLBP subjects, which
      resulted in increased pain in the low back area.

PMID- 11581548
TI  - Prediction of maximal heart rate in individuals with mental retardation.
AB  - PURPOSE: It is well known that individuals with mental retardation (MR),
      especially those with Down syndrome (DS), have low maximal heart rates (MHR). We
      evaluated the ability to predict MHR in individuals with MR and DS in comparison
      with persons without MR. METHODS: Subjects completed a maximal exercise test on
      the treadmill with metabolic and HR measurements. Stepwise multiple regression
      was used to develop prediction equations for subjects with MR (N = 276; 97 with
      DS) and without (N = 296) MR, ranging in age from 9-46 yr. RESULTS: Subjects with
      MR exhibited significantly lower MHR (177 vs 185 beats.min(-1)) and VO2peak (33.8
      vs 35.6 mL.kg-1.min(-1)). In subjects with MR, age was a poor predictor of MHR, Y
      = 189 - 0.59 (age) (R = 0.30, SEE = 13.8 beats.min-1; P < 0.01), but age was a
      better predictor for subjects without MR, Y = 205 - 0.64 (age) (R = 0.52, SEE =
      9.9 beats.min(-1); P < 0.01). A large sample Z test indicated that these
      regression coefficients were significantly different (P < 0.01). However, adding
      DS to the regression improved the prediction for subjects with MR, Y = 210 -
      (0.56 age) - (15.5 DS) (R = 0.57; SEE = 11.8 beats.min(-1), P < 0.01).
      CONCLUSION: MHR can be predicted with similar accuracy in subjects with and
      without MR, provided DS is accounted for in the equation for the subjects with
      MR.

PMID- 11581549
TI  - Blood lipids in young distance runners.
AB  - PURPOSE: The purpose of this study was to examine the age-and sex-associated
      variation in blood lipids among young athletes. METHODS: A mixed-longitudinal
      design was used to examine the development of blood lipids in competitive young
      distance runners followed from 1982 to 1985. Serial data included 99 annual
      measurements for 27 male subjects and 84 annual measurements for 27 female
      subjects aged 9-18 yr. Total cholesterol (TC), high-density lipoprotein (HDL-C),
      low-density lipoprotein (LDL-C), and triglycerides (TG) were determined by
      standard procedures. RESULTS: In general, cross-sectional age group means showed
      that TC and LDL-C remained stable and HDL-C declined with age, especially in male
      subjects. TG increased with age. Age-related trends were statistically
      significant for HDL-C and TG in boys only (P < 0.05). TC and LDL-C were slightly
      greater in boys at all ages except 11, 15, and 17 yr (P > 0.05). HDL-C was
      similar between the sexes until 13 yr when values became greater in girls (3.2
      13.8 mg.dL(-1)) (P < 0.05 in 17+ yr). No clear pattern of sex differences emerged
      for TG. Compared with the general population, blood lipids of young distance
      runners showed the following trends: 1) TC was above reference medians, 2) LDL-C
      tended to approximate or to be slightly above reference medians, 3) TG fluctuated
      about the reference medians, and 4) HDL-C was higher in distance runners compared
      to the reference medians before age 14 yr, but in the older age groups,
      especially male subjects, HDL-C either approximated or fell slightly below the
      reference medians. There was considerable variability in blood lipid levels among
      the runners. In 21 male and 18 female subjects with serial data for 3-5 yr, HDL-C
      declined 22.4 and 18.3 mg.dL(-1) (P < 0.05), whereas TG increased 18.0 and 14.0
      mg.dL(-1)(P < 0.05 in female subjects only) in male and female subjects,
      respectively. Tracking coefficients over intervals of 3-5 yr were moderate to
      high (0.48-0.90), except for TG in male subjects (0.08). CONCLUSIONS: The results
      indicate that the development of blood lipids in young distance runners is
      similar to youth in the general population. In contrast to observations in adult
      endurance athletes, young distance runners did not possess a superior blood lipid
      profile except for HDL-C in the younger age groups.

PMID- 11581550
TI  - Creatine supplementation during resistance training in college football athletes.
AB  - PURPOSE: This investigation assessed the effects of a 9-wk regimen of creatine
      monohydrate (Cr x H2O) supplementation coupled with resistance training on body
      composition and neuromuscular performance in NCAA Division I football athletes.
      METHODS: Twenty-five subjects were randomly assigned in a double-blind,
      randomized placebo-controlled design, to a treatment (Cr, N = 9), placebo (P, N =
      8), or control group (C, N = 8). The Cr group received 20 g.d(-1) of creatine for
      the first 5 d in 5-g doses, four times daily, followed by 5 g.d(-1) for the
      remainder of the study. Each 5-g dose was mixed with 500 mL of glucose solution
      (Gatorade). The P group received a placebo (sodium phosphate monohydrate; NaH2PO4
      x H2O) following the exact protocol as the Cr group. The C group received no
      supplementation. All subjects resistance trained 4 d.wk(-1). Measurements of
      neuromuscular performance and body composition were made pre- and post-training
      after supplementation while monitoring dietary intakes. RESULTS: Repeated
      measures ANOVA indicated significant differences occurred between the Cr group
      and the other two groups (P and C) for total body weight, lean body mass, cell
      hydration, strength, peak torque at 300 degrees.s(-1) knee flexion, percent
      torque decrement, and anaerobic power and capacity. However, percent body fat,
      peak torque during both knee flexion and extension at 60 and 180 degrees.s(-1),
      peak torque at 300 degrees.s(-1) during knee extension, global muscular strength
      (power clean), and extracellular fluid remained statistically unchanged for all
      groups. CONCLUSIONS: Our findings indicate that creatine, supplemented
      concurrently with resistance and anaerobic training, may positively affect cell
      hydration status and enhance performance variables further than augmentation seen
      with training alone.

PMID- 11581551
TI  - Effects of oral creatine and resistance training on myosin heavy chain
      expression.
AB  - PURPOSE: This study examined 12 wk of creatine (Cr) supplementation and heavy
      resistance training on muscle strength and myosin heavy chain (MHC) isoform mRNA
      and protein expression. METHODS: Twenty-two untrained male subjects were randomly
      assigned to either a control (CON), placebo (PLC), or Cr (CRT) group in a double
      blind fashion. Muscle biopsies were obtained before and after 12 wk of heavy
      resistance training. PLC and CRT trained thrice weekly using three sets of 6-8
      repetitions at 85-90% 1-RM on the leg press, knee extension, and knee curl
      exercises. CRT ingested 6 g.d-1 of Cr for 12 wk, whereas PLC consumed the equal
      concentration of placebo. RESULTS: There were no significant differences for
      percent body fat (P > 0.05). However, for total body mass, fat-free mass, thigh
      volume, muscle strength, and myofibrillar protein, CRT and PLC exhibited
      significant increases after training when compared to CON (P < 0.05), whereas CRT
      was also significantly greater than PLC (P < 0.05). For Type I, IIa, and IIx MHC
      mRNA expression, CRT was significantly greater than CON and PLC, whereas PLC was
      greater than CON (P < 0.05). For MHC protein expression, CRT was significantly
      greater than CON and PLC for Type I and IIx (P < 0.05) but was equal to PLC for
      IIa. CONCLUSION: Long-term Cr supplementation increases muscle strength and size,
      possibly as a result of increased MHC synthesis.

PMID- 11581552
TI  - High femoral bone mineral content and density in male football (soccer) players.
AB  - PURPOSE: This investigation examined the effect that long-term football (soccer)
      participation may have on areal bone mineral density (BMD) and bone mineral
      content (BMC) in male football players. METHODS: Dual energy x-ray absorptiometry
      (DXA) scans were obtained in 33 recreational male football players active in
      football for the last 12 yr and 19 nonactive subjects from the same population.
      Both groups had comparable age (23 +/- 4 yr vs 24 +/- 3 yr), body mass (73 +/- 7
      kg vs 72 +/- 11 kg), height (176 +/- 5 cm vs 176 +/- 8 cm), and calcium intake
      (23 +/- 10 mg.kg(-1).d(-1) vs 20 +/- 11 mg.kg(-1).d(-1) (mean +/- SD). RESULTS:
      The football players showed 8% greater total lean mass (P < 0.001), 13% greater
      whole-body BMC (P < 0.001), and 5 units lower percentage body fat (P < 0.001)
      than control subjects. Lumbar spine (L2-L4) BMC and BMD were 13% and 10% higher,
      respectively, in the football players than in the control subjects (P < 0.05).
      Furthermore, football players displayed higher femoral neck BMC (24%, 18%, 23%,
      and 24% for the femoral neck, intertrochanteric, greater trochanter, and Ward's
      triangle subregions, respectively, P < 0.05) and BMD (21%, 19%, 21%, and 27%,
      respectively, P < 0.05) than controls. BMC in the whole leg was 16-17% greater in
      the football players, mainly because of enhanced BMD (9-10%) but also because of
      bone hypertrophy, since the area occupied by the osseous pixels was 7% higher
      (867 +/- 63 cm2 vs 814 +/- 26 cm2, P < 0.05). Leg muscle mass was 11% higher in
      the football players than in the control subjects (20,635 +/- 2,073 g vs 18,331
      +/- 2,301 g, P < 0.001). No differences were found between the legs in either
      groups for BMC, BMD, and muscle mass. Left leg muscle mass was correlated with
      femoral neck BMC and BMD (P < 0.001), as well as with lumbar spine (L2-L4) BMC
      and BMD (P < 0.001). CONCLUSION: Long-term football participation, starting at
      prepubertal age, is associated with markedly increased BMC and BMD at the femoral
      neck and lumbar spine regions.

PMID- 11581553
TI  - Effect of testosterone administration and weight training on muscle architecture.
AB  - PURPOSE: The purpose of this study was to assess muscle architecture changes in
      subjects who were administered supraphysiologic doses of testosterone enanthate
      (TE) and concurrently performed heavy resistance training. METHODS: Ten subjects
      were randomly selected from the 21 subjects who participated in a previously
      published study (12). Subjects were allocated to one of two groups as per Giorgi
      et al. (12) and received either a saline-based placebo (nonTE) or a 3.5-mg.kg-1
      body weight dose of TE by deep intramuscular injection once a week for 12 wk.
      Subjects also performed heavy resistance training using exercises that targeted
      the triceps brachii muscle. Before and after the training period, free-weight one
      repetition-maximum (1-RM) bench press strength was tested, muscle thickness and
      pennation of the triceps brachii lateralis were measured using ultrasound
      imaging, and fascicle length was estimated from ultrasound photographs. RESULTS:
      There were no significant between-group differences in muscle thickness changes
      despite a trend toward increased thickness in TE subjects (TE, 23.5%, vs nonTE,
      13.8%). However, 1-RM bench press performance and muscle pennation increased
      significantly in TE subjects compared with nonTE subjects (P < 0.05). There was
      also a trend toward longer fascicle lengths in the muscles of nonTE subjects.
      CONCLUSION: The results of the present study suggest that the use of TE in
      conjunction with heavy resistance training is associated with muscle architecture
      changes that are commonly associated with high-force production. Since there was
      little difference between the groups in muscle thickness, changes in pennation
      and possibly fascicle length may have contributed to strength gains seen in TE
      subjects.

PMID- 11581554
TI  - Effects of dehydration and rehydration on EMG changes during fatiguing
      contractions.
AB  - PURPOSE: This study measured the effects of sauna-induced dehydration (Dhy) and
      the effectiveness of rapid rehydration on muscle performance and EMG frequency
      spectrum changes associated with fatigue during isometric contractions. METHODS:
      Knee extensor muscle strength during isometric maximal voluntary contraction
      (MVC) and endurance time at 25% and 70% of MVC (ET25 and ET70, respectively) were
      measured three times in 11 healthy male subjects, under euhydration conditions
      (Eu), after Dhy, and after rehydration following Dhy (Rhy). RESULTS: Dhy led to a
      decrease in body weight by 2.95 +/- 0.05%. No significant effect of the hydration
      status was shown on MVC values. A 23% decrease in ET25 was recorded during Dhy (P
      < 0.01), whereas ET70 only tended to decrease (-13%, P = 0.06). ET25 was higher
      during Rhy than Dhy (8%, P < 0.05) but remained lower than during Eu (-17%, P <
      0.05). The EMG root mean square (RMS) increased earlier during Dhy than Eu.
      Opposite changes were shown for the mean power frequency (MPF) of EMG, and Dhy
      resulted in an accelerated fall in MPF. However, because ET25 decreased with
      dehydration, RMS and MPF changes were similar during Eu and Dhy when reported to
      normalized contraction time, exhaustion was thus associated with similar values
      of RMS and MPF for all conditions. RMS and MPF changes during Rhy showed an
      intermediate pattern between Eu and Dhy. CONCLUSIONS: Dhy induced an increase in
      muscle fatigue, associated with early changes in EMG spectral parameters. It is
      not clear whether these alterations could be attributed to biochemical
      modifications, and the role of increased perception of effort when subjects were
      dehydrated should be clarified.

PMID- 11581555
TI  - Overuse injuries in youth sports: biomechanical considerations.
AB  - Many children today participate in highly organized sports programs that involve
      regimented year-round repetitive training. This type of training has led to an
      increased incidence of overuse musculoskeletal injuries. Sports physicians have
      dealt with sports injuries in children for many years and, on the basis of their
      clinical experience, have developed guidelines to treat and to try and prevent
      these injuries. The purpose of this article is to provide a biomechanical
      perspective of sports injuries in young athletes and blend ideas from this
      perspective with more traditional clinical perspectives that dominate the
      literature relative to this topic. Basic tissue and gross movement mechanics
      principles are used to identify growth, morphological, and movement factors that
      may predispose a child to an overuse injury. Several biomechanical analyses of
      simple movement tasks are presented to quantify the forces developed in various
      tissues and to illustrate the effects that growth can have on these forces.
      Guidelines are given for developing injury prediction models that may be used in
      the future to establish safe and effective training guidelines for children.

PMID- 11581556
TI  - The effects of joint angle and reliability on knee proprioception.
AB  - PURPOSE: The purpose of this study was to examine the reliability and effects of
      knee angle on the detection and subsequent response to passive knee movement.
      METHODS: Twenty college-aged male and 20 female volunteers were evaluated for
      proprioception by a newly developed perturbation test. Subjects were in a prone
      position on an isokinetic chair with their right lower leg attached to a freely
      moving resistance adapter. The knee was placed in a starting position of 15, 30,
      or 60 degrees of flexion. While relaxed, the knee was dropped into extension, and
      the subjects were instructed to "catch their leg" when movement was perceived.
      Five trials were completed at each angle, in a random order. An electrogoniometer
      was secured to the lateral portion of the knee in order to measure angular
      displacement after perturbation in two specific phases: detection (displacement
      from leg release to movement cessation) and response (displacement from movement
      cessation to peak knee flexion). A three-factor ANOVA (two repeated factors (knee
      angle and proprioception phase) and one between factor (gender)) was performed on
      the average and standard deviation of the five trials for significant main
      effects and interactions. RESULTS: The results demonstrated a significant phase
      by angle interaction, and no gender effect. It was shown that at a more extended
      knee joint position (15 degrees), significantly less knee movement occurred
      before perception, followed by a greater response, than in a more flexed position
      (30 and 60 degrees). CONCLUSION: The major findings of this study suggest that
      the detection of passive knee movement, and the subsequent voluntary response,
      may be dependent on joint angle. Considerations of the present method for
      proprioception assessment are warranted to enhance test-retest reliability.

PMID- 11581557
TI  - Electromyographic activity and applied load during seated quadriceps exercises.
AB  - PURPOSE: The aim of this study was to quantify and compare mean quadriceps muscle
      activity and applied load for eight seated quadriceps exercises using four types
      of resistance. METHODS: Using surface electromyography (EMG), the right rectus
      femoris (RF), vastus lateralis (VL), and vastus medialis oblique (VMO) muscles of
      52 university students aged 23.5 +/- 3.4 yr (35 female and 17 male subjects) were
      examined during the exercises. Resistance devices included an ankle weight (78
      N), blue Thera-Band tubing, a Cybex 340 isokinetic dynamometer, and an Inertial
      Exercise Trainer (IET). Electrogoniometer data were collected to determine the
      range of motion (ROM), angular velocity, and phase (concentric/eccentric) of
      exercise. Load cell data were analyzed to determine tubing and IET applied loads
      during exercise. A within-subjects criterion was used to improve intrasubject EMG
      reliability. All EMG values were normalized to a 100% maximum voluntary isometric
      contraction. Repeated measures ANOVAs with Bonferroni comparisons were used for
      statistical analysis. RESULTS: Within-subject effects of muscle and exercise were
      significant (P < 0.05) for both the concentric and eccentric muscle activity. The
      interaction effect of mean average EMG amplitude across exercises for the
      concentric phases of knee extension was significant (P = 0.001). No significant
      interactions were found for the eccentric phases of all seated quadriceps
      exercises. None of the exercises selectively isolated the VMO over the VL;
      however, the VMO/VL ratio was less (P < 0.05) during the concentric phases of the
      free weight and elastic tubing exercise when compared with the others. Eccentric
      phase VMO/VL ratios revealed that inertial resistance elicited greater muscle
      activity than other forms of resistance exercise. CONCLUSION: These findings
      suggest clinicians should consider biomechanical and resistance data when
      developing a strengthening program for the quadriceps muscle. Some seated
      quadriceps exercises may be more appropriate for certain rehabilitation goals
      than others.

PMID- 11581558
TI  - %HRmax target heart rate is dependent on heart rate performance curve deflection.
AB  - The percent of maximal heart rate (%HRmax) model is widely used to determine
      training intensities in healthy subjects and patients when prescribing training
      intensities in these groups of subjects. PURPOSE: The aim of the study was to
      investigate the influence of the time course of the heart rate performance curve
      (HRPC) on the accuracy of target training heart rate. METHODS: Sixty-two young
      healthy male subjects performed an incremental cycle ergometer exercise test
      until voluntary exhaustion. Subjects were then divided into four groups according
      to the time course of the HRPC. Groups were classified in regular HR response
      (kHR2 > 0.2), indifferent HR response (0 < kHR2 < 0.2), linear HR response (kHR2
      = 0), and inverted HR response (kHR2 < 0). The first and the second lactate turn
      point (LTP1, LTP2) as well as the heart rate turn point (HRTP) were determined as
      submaximal markers of performance. Linear regression lines were calculated for HR
      in the three regions of energy supply defined by LTP1 and LTP2. RESULTS: HR at
      LTP1 and HRmax was not significantly different between all four groups. HR at
      LTP2 was dependent on the time course of the HRPC and was significantly lower (P
      < 0.05) as kHR2 decreased. Power output and blood lactate concentration at LTP1,
      LTP2 and maximal workload (Pmax) were not significantly different between the
      groups. CONCLUSION: From our data, we conclude that target training HR detected
      by means of the %HRmax method may be overestimated in cases where the HR response
      is not regular, as it was found in many of our subjects.

PMID- 11581559
TI  - Effects of a 7-day eccentric training period on muscle damage and inflammation.
AB  - PURPOSE: This study examined the effects of a 7-d repeated maximal isokinetic
      eccentric training period on the indicators of muscle damage and inflammatory
      response. METHODS: Twenty-two college-age males were randomly assigned to
      eccentric training (ET) (N = 12) and control groups (CON) (N = 10). The initial
      exercise was 30 repetitions of maximal voluntary isokinetic eccentric contraction
      (ECC1) on nondominant elbow flexors with Cybex 6000 at 60 degrees.s-1 angular
      velocity. The ET group performed the same exercise for the following 6
      consecutive days (referred to as ECC2 to ECC7) after ECC1. Upper arm
      circumference (CIR), range of motion (ROM), and maximal isometric force (MIF)
      were measured before, immediately after, and every 24 h for 7 consecutive days
      after ECC1. Plasma creatine kinase (CK), lactate dehydrogenase (LDH), glutamic
      oxaloacetate transaminase (GOT), leukocyte counts, and serum interleukin-1beta
      and -6 (IL-1beta, IL-6) levels were assessed before; at 2 h; and at 1, 3, 4, 6,
      and 7 d after ECC1. Muscle soreness was measured before and for 7 consecutive
      days after ECC1. RESULTS: The ECC1 produced significant changes in most of the
      measures for both groups (P < 0.05), with the exception of leukocyte counts (P >
      0.05). No indicators of increased damage (P > 0.05) were found from ECC2 to ECC7
      for the ET group. CONCLUSION: Continuous intensive isokinetic eccentric training
      performed with damaged muscles did not exacerbate muscle damage and inflammation
      after ECC1. In addition, a muscular "adaptation effect" may occur as early as 24
      h after ECC1, as shown by the ET group's performance for 6 consecutive days after
      ECC1.

PMID- 11581560
TI  - Hemoglobin, muscle oxidative capacity, and VO2max in African-American and
      Caucasian women.
AB  - PURPOSE: The purpose of this paper was to determine whether differences in
      hemoglobin (Hb) and muscle aerobic capacity exist between African-American (AA)
      and Caucasian (CA) premenopausal women and to determine whether Hb and aerobic
      capacity of the muscle are associated with the racial differences in maximum
      oxygen uptake (VO2max). METHODS: 43 AA and 46 CA sedentary premenopausal women
      were subjects. Percent body fat was determined by four-compartment model, leg
      lean tissue by dual energy x-ray absorptiometry, VO2max during a graded exercise
      test, aerobic capacity of the calf muscle by 31P magnetic resonance spectroscopy,
      and serum Hb by the cyanide method. RESULTS: AA women had reduced VO2max (AA 29.3
      +/- 3.0 vs CA 33.6 +/- 5.6 mL.kg(-1) bdw(-1).min, P < 0.01), reduced muscle
      aerobic capacity (AA 24.3 +/- 5.8 vs CA 21.3 +/- 4.8 s, P = 0.01, where lower
      values indicate higher aerobic capacity), and reduced Hb (AA 11.8 +/- 1.3 vs CA
      12.9 +/- 0.8 g.dL(-1), P < 0.01). The racial difference in VO2max persisted
      whether the values were unadjusted or adjusted for fat-free mass or leg lean
      tissue. Multiple regression analysis revealed that both Hb and muscle aerobic
      capacity were related to VO2max after adjusting for each other, race, and either
      fat-free mass or leg lean tissue. Being AA was associated with reduced VO2max in
      mL O2.kg leg lean tissue(-1).min(-1) (zero-order simple Pearson-product
      correlation -0.60, P < 0.01). When multiple regression was used, the correlation
      between race and VO2max decreased but persisted (-0.40, <0.01) after adjusting
      for Hb and muscle aerobic capacity. CONCLUSIONS: These data suggest that
      differences in Hb and aerobic capacity of muscle are related to reduced VO2max in
      AA women. However, Hb and aerobic capacity of the muscle can only partially
      explain the racial differences in VO2max.

PMID- 11581561
TI  - A longitudinal assessment of change in VO2max and maximal heart rate in master
      athletes.
AB  - PURPOSE: The purpose of this study was to determine the longitudinal change in
      VO2max and HRmax in male and female master endurance runners and to compare these
      changes based upon gender, age, and change in training volume. METHODS: Eighty
      six male (53.9 +/- 1.1 yr) and 49 female (49.1 +/- 1.2 yr) master endurance
      runners were tested an average of 8.5 yr apart. Subjects were grouped by age at
      first visit, change in VO2max, and change in training volume. Measurements
      included body composition by hydrostatic weighing, maximal exercise testing on a
      treadmill, and training history by questionnaire. Data were analyzed by ANOVA and
      multiple regression. RESULTS: VO2max and HRmax declined significantly regardless
      of gender or age group (P < 0.05). The rate of change in VO2max by age group
      ranged from -1% to -4.6% per year for men and -0.5% to 2.4% per year for women.
      Men with the greatest loss in VO2max had the greatest loss in LBM (-2.8 +/- 0.7
      kg), whereas women with the greatest loss in VO2max demonstrated the greatest
      change in training volume (-24.1 +/- 3.0 km.wk-1). Additionally, women with the
      greatest loss in VO2max (-9.6 +/- 2.6 mL.kg-1.min-1) did not replace estrogen
      after menopause independent of age. HRmax change did not differ by VO2max change
      or training volume change in either gender. CONCLUSIONS: In conclusion, these
      data suggest that VO2max declines in male and female master athletes at a rate
      similar to or greater than that expected in sedentary older adults. Additionally,
      these data suggest that maintenance of LBM and VO2max were associated in men,
      whereas in women, estrogen replacement and maintenance of training volume were
      associated with maintained VO2max.

PMID- 11581562
TI  - Concurrent cardiovascular and resistance training in healthy older adults.
AB  - PURPOSE: The recommendations for exercise training and physical activity for
      older adults include cardiovascular and resistance training components (CVT and
      RT, respectively). The purpose of the present investigation was to compare the
      fitness benefits of concurrent CVT and RT with those attained through an
      equivalent duration of CVT or RT alone. METHODS: Thirty-six participants (ages 60
      84) were assigned to a control group or to one of three exercise treatment
      groups. The treatment groups exercised three times per week for 12 wk using RT (N
      = 11), CVT (N = 10), or CVT and RT (BOTH, N = 9). Pre- and post-training,
      participants performed a submaximal exercise test (GXT), five repetition-maximum
      strength tests (5RM), and the AAHPERD functional fitness test for older adults.
      RESULTS: All exercise treatment groups revealed lower resting heart rate and rate
      pressure product; lower exercise diastolic blood pressure and rating of perceived
      exertion; increased GXT duration; increased leg, back, and shoulder 5RM scores;
      and improved AAHPERD flexibility, coordination, and cardiovascular endurance
      scores. The exercise treatment groups responded differently on the following: RT
      and BOTH enhanced arm and chest strength more than CVT; and BOTH enhanced AAHPERD
      strength and agility scores more than CVT or RT. CONCLUSIONS: Concurrent CVT and
      RT is as effective in eliciting improvements in cardiovascular fitness and 5RM
      performance as CVT or RT, respectively. Moreover, incorporating both CVT and RT
      in exercise programs for older adults may be more effective in optimizing aspects
      of functional fitness than programs that involve only one component.

PMID- 11581563
TI  - High-resistance versus variable-resistance training in older adults.
AB  - PURPOSE: The purpose of this study was to compare the effects of high-resistance
      (HR) training, 3 times.wk(-1) at 80% maximum strength (1RM) with 3 times.wk(-1)
      variable-resistance (VR) training (once-weekly training at 80%, 65%, and 50% 1RM)
      in older adults. METHODS: The study was a 6-month resistance training
      intervention conducted in the Birmingham Alabama metropolitan area, and included
      healthy volunteer men and women over the age of 60. Twenty-eight subjects were
      assigned randomly to two training groups. Eight volunteers served as controls.
      Before and after 25 wk of training, body composition was measured by
      densitometry; strength by isometric tests; and difficulty in performing daily
      activity tasks (DAT) by measuring heart rate, oxygen uptake, electromyography,
      and perceived exertion. In addition, 1RM strength was measured every 25 d
      throughout the 6 months of training. Repeated measures ANOVA and paired t-tests
      with Bonferroni corrections for additive alpha were used to analyze the data.
      RESULTS: The control group did not significantly change in any study parameter.
      No significant change in body weight occurred for any group. However, the HR and
      VR groups increased fat free mass (FFM) similarly (1.8 kg and 1.9 kg,
      respectively). Both training groups increased strength significantly, without
      significant differences in change. No significant change in oxygen uptake
      occurred during DAT. However, there was a significant time effect for heart rate
      and perceived exertion. Greater decrease in normalized integrated
      electromyography during the carry task was found in the VR group over the HR and
      control groups. CONCLUSION: Despite similar increases in strength and fat free
      mass, the VR group decreased difficulty of performing the carry task more than
      the HR group. These data suggest that larger improvements in DAT may be achieved
      if frequency of high-resistance training is less than 3 times.wk(-1).

PMID- 11581564
TI  - Reciprocal strength ratio in shoulder abduction/adduction in sports and daily
      living.
AB  - PURPOSE: Functionally, the shoulder is considered a ball joint, whereby high
      mobility is attended by low stability. Therefore, muscular balance is decisive
      for stability. Altered strength ratios are frequently described as "muscular
      dysbalances" and considered one of the causes of shoulder pathologies, whereby
      objective quantification is difficult. METHODS: In order to quantify
      physiological muscle balance, the strength ratio of shoulder abduction/adduction
      (AB/AD) was determined in 166 untrained men (UM) concentrically at 60 degrees.s-1
      (LIDO-Active). The influence on this norm of one-sided (25 high-performance
      (TPH), 18 leisure tennis players (TPL)) and two-sided athletic exercise (32
      gymnasts (GY)), altered daily exercise (11 paraplegics with paralysis time < 4
      months (PP), 11 paraplegics with paralysis time > 2 yr (PU)), and a combination
      of altered daily exercise and athletic activity (16 trained paraplegics (PT)) was
      examined (ANOVA, alpha = 0.05). RESULTS: Determination of the AB/AD quotient in
      UM was 0.82. Shoulder stress in sports led to a decrease in quotients compared
      with UM because of a relatively increased torque in AD (P < 0.01). At the
      beginning of a paraplegia, the quotient of AB/AD is elevated (P < 0.05). This
      altered ratio decreases with duration of paralysis (PU) and athletic activity
      (PT). CONCLUSION: With increased shoulder stress, the altered strength ratios
      reflect specific requirements of the performance attained. However, the
      importance of muscular dysbalances for the onset of shoulder complaints must be
      considered more important than their influence on athletic performance capacity.

PMID- 11581565
TI  - Evaluating the reproducibility and validity of the Aerobic Adaptation Test.
AB  - PURPOSE: To examine the reproducibility and validity of a new submaximal, ramped
      cycle ergometer testing methodology known as the Aerobic Adaptation Test (AAT),
      which attempts to detect changes in submaximal work capacity and minimize
      participant discomfort. METHODS: 36 sedentary men (mean age = 48.1 +/- 10.2 yr
      [SD]) and 22 sedentary women (mean age = 51.9 +/- 10.2 yr [SD]) participated in
      the study. To test reproducibility, participants were tested twice with an
      average of 20 d between tests (+/-15 d). To test validity, participants were
      tested before and after a 6-month physical activity intervention, and outcomes
      were compared with standard measures of fitness (exercise time and oxygen
      consumption at 70% max heart rate). The main outcome variable of the AAT was work
      output (W) over a period of 3 min after reaching 70% maximal heart rate. RESULTS:
      The average work output at 70% HRmax was highly reproducible, with a test-retest
      reliability of rho = 0.85 (P < 0.001). Average work output at 70% HRmax
      significantly increased after 6 months of physical activity intervention (87.8 +/
      32.9 W vs 95.5 +/- 37.9 W, P = 0.002), and changes in average work output at 70%
      HRmax correlated with changes in exercise time to elicit 70% HRmax (r = 0.87, P <
      0.001) as well as changes in VO2 at 70% HRmax (r = 0.75, P < 0.001). Thus, the
      AAT appears to be a valid measure of submaximal work capacity. CONCLUSIONS: The
      AAT is a reproducible and valid measure of submaximal work capacity that can
      serve as an effective means to evaluate physical activity interventions.

PMID- 11581566
TI  - Studies of a targeted risk reduction intervention through defined exercise
      (STRRIDE).
AB  - PURPOSE: The Studies of a Targeted Risk Reduction Intervention through Defined
      Exercise (STRRIDE) trial is a randomized controlled clinical trial designed to
      study the effects of exercise training regimens differing in dose (kcal.wk-1)
      and/or intensity (relative to peak VO2) on established cardiovascular risk
      factors and to investigate the peripheral biologic mechanisms through which
      chronic physical activity alters carbohydrate and lipid metabolism to result in
      improvements in these parameters of cardiovascular risk in humans. METHODS: We
      will recruit 384 subjects and randomly assign them to one of three exercise
      training regimens or to a sedentary control group. The recruiting goal is to
      attain a subject population that is 50% female and 30% ethnic minority. The
      overall strategy is to use graded exercise training regimens in moderately
      overweight subjects with impairments in insulin action and mild to moderate lipid
      abnormalities to investigate whether there are dose or intensity effects and
      whether adaptations in skeletal muscle (fiber type, metabolic capacity, and/or
      capillary surface area) account for improvements in insulin action and parameters
      of lipoprotein metabolism. We will study these variables before and after
      exercise training, and over the course of a 2-wk detraining period. The study
      sample size is chosen to power the study to examine differences in responses
      between subjects of different gender and ethnicity to exercise training with
      respect to the least sensitive parameter-skeletal muscle capillary density.
      RESULTS: The driving hypothesis is that improvements in cardiovascular risk
      parameters derived from habitual exercise are primarily mediated through
      adaptations occurring in skeletal muscle. CONCLUSION: Identification that amount
      and intensity of exercise matter for achieving general and specific health
      benefits and a better understanding of the peripheral mechanisms mediating the
      responses in carbohydrate and lipid metabolism to chronic physical activity will
      lead to better informed recommendations for those undertaking an exercise program
      to improve cardiovascular risk.

PMID- 11581567
TI  - The accuracy of the ACSM stair-stepping equation.
AB  - PURPOSE: The purpose of this study was to determine the accuracy of the ACSM
      equation used to estimate the oxygen cost of stepping exercise. The equation
      appears as: VO2 (mL.kg(-1).min(-1)) = 0.2 (steps.min(-1)) + (step height, m x
      steps.min(-1) x 2.4) + 3.5. METHODS: Subjects were 55 men and women between the
      ages of 19 and 35 yr. Steady-state VO2 was measured at six different combinations
      of step heights and step rates. Step heights were 0.1, 0.2, and 0.3 m (4, 8, and
      12 in, respectively) and step rates were 20 and 25 steps.min(-1). Predicted VO2
      for each workload was derived from the ACSM equation. RESULTS: Mean differences
      between actual and predicted VO2 values ranged from -0.2 to -1.1 mL.kg(-1).min(
      1) and was -0.6 mL.kg(-1).min(-1) for all workloads combined. All differences
      except the lowest were significant (P < or = 0.05). Total errors ranged from 1.3
      to 2.5 mL.kg(-1).min(-1) and was 1.9 mL.kg(-1).min(-1) for all workloads
      combined. For all workloads combined, the correlation between actual and
      predicted VO2 was r = 0.95 with a SEE = 1.7 mL.kg(-1).min(-1). The statistics are
      comparable to other ACSM prediction equations. CONCLUSION: Although all of the
      mean differences except one were statistically significant, they were judged
      negligible from a practical standpoint. Therefore, it was concluded that the ACSM
      equation is an accurate predictor of the oxygen cost of stair-stepping exercise.

PMID- 11581568
TI  - The team physician and conditioning of athletes for sports: a consensus
      statement.

PMID- 11581569
TI  - The reliability of cycling maximal accumulated oxygen deficit (MAOD) and time to
      exhaustion (T(lim)) in untrained subjects.

PMID- 11581570
TI  - Bacterial lipopolysaccharides and innate immunity.
AB  - Bacterial lipopolysaccharides (LPS) are the major outer surface membrane
      components present in almost all Gram-negative bacteria and act as extremely
      strong stimulators of innate or natural immunity in diverse eukaryotic species
      ranging from insects to humans. LPS consist of a poly- or oligosaccharide region
      that is anchored in the outer bacterial membrane by a specific carbohydrate lipid
      moiety termed lipid A. The lipid A component is the primary immunostimulatory
      centre of LPS. With respect to immunoactivation in mammalian systems, the
      classical group of strongly agonistic (highly endotoxic) forms of LPS has been
      shown to be comprised of a rather similar set of lipid A types. In addition,
      several natural or derivatised lipid A structures have been identified that
      display comparatively low or even no immunostimulation for a given mammalian
      species. Some members of the latter more heterogeneous group are capable of
      antagonizing the effects of strongly stimulatory LPS/lipid A forms. Agonistic
      forms of LPS or lipid A trigger numerous physiological immunostimulatory effects
      in mammalian organisms, but--in higher doses--can also lead to pathological
      reactions such as the induction of septic shock. Cells of the myeloid lineage
      have been shown to be the primary cellular sensors for LPS in the mammalian
      immune system. During the past decade, enormous progress has been obtained in the
      elucidation of the central LPS/lipid A recognition and signaling system in
      mammalian phagocytes. According to the current model, the specific cellular
      recognition of agonistic LPS/lipid A is initialized by the combined extracellular
      actions of LPS binding protein (LBP), the membrane-bound or soluble forms of CD14
      and the newly identified Toll-like receptor 4 (TLR4)*MD-2 complex, leading to the
      rapid activation of an intracellular signaling network that is highly homologous
      to the signaling systems of IL-1 and IL-18. The elucidation of structure-activity
      correlations in LPS and lipid A has not only contributed to a molecular
      understanding of both immunostimulatory and toxic septic processes, but has also
      re-animated the development of new pharmacological and immunostimulatory
      strategies for the prevention and therapy of infectious and malignant diseases.

PMID- 11581571
TI  - Up-regulation of gastric mucosal inflammatory responses to Helicobacter pylori
      lipopolysaccharide by aspirin but not indomethacin.
AB  - Infection with Helicobacter pylori and the use of non-steroidal anti-inflammatory
      drugs (NSAIDs) are recognized as the two primary factors in the etiology of
      gastric disease. In this study, we applied the animal model of H. pylori-induced
      gastritis to assess the influence of NSAIDs on the course of mucosal inflammatory
      responses to H. pylori. Two days following intragastric application of H. pylori
      lipopolysaccharide, rats were divided into groups and administered daily for up
      to 8 days either indomethacin, aspirin or the vehicle, and their gastric mucosal
      tissue subjected to histological and biochemical assessment. H. pylori
      lipopolysaccharide elicited within 2 days a pattern of acute mucosal inflammatory
      responses accompanied by a massive epithelial cell apoptosis, and a marked
      increase in the expression of membrane-bound and soluble forms of TNF-alpha. The
      extent of mucosal inflammatory involvement reached a maximum by the 4th day and
      showed a decline by the 10th day; this was reflected in a 38.1% reduction in
      apoptosis, a 53.2% decline in membrane-bound TNF-alpha and a 63.8% decrease in
      soluble TNF-alpha. Compared to the vehicle controls, aspirin caused a 36.2%
      increase in the severity of the mucosal inflammatory involvement by the second
      day of administration and a 25.9% increase in the inflammatory involvement
      occurred by the 8th day; this effect of aspirin was accompanied by a significant
      (54.5%) induction in apoptosis, a 58.2% decline in membrane-bound TNF-alpha and a
      61% increase in soluble TNF-alpha. In contrast, administration of indomethacin
      evoked only a marginal increase (5-7%) in apoptosis, and caused no discernible
      changes in the severity of gastric mucosal involvement and the expression of TNF
      alpha forms elicited by H. pylori lipopolysaccharide. The findings indicate that
      aspirin, but not indomethacin, increases the severity of gastric mucosal
      inflammatory responses to H. pylori. This detrimental influence of aspirin
      appears to result from up-regulation in the mucosal expression of soluble form of
      TNF-alpha, which leads to the amplification of apoptotic events that potentiate
      gastric mucosal inflammatory reaction to H. pylori.

PMID- 11581572
TI  - Porins from Salmonella typhimurium accelerate human blood coagulation in vitro by
      selective stimulation of thrombin activity: implications in septic shock DIC
      pathogenesis.
AB  - The effect of porins, major hydrophobic outer membrane proteins purified from
      Salmonella typhimurium, on human blood coagulation was investigated. It was found
      that micromolar concentrations of porins accelerated markedly human blood
      coagulation in vitro. Using appropriate experiments, data were obtained showing
      that the main target of the porin-induced procoagulant effect was thrombin. A
      possible binding of porins with thrombin has been suggested to be the basis of
      this effect. The implications of this finding in the pathogenesis of the
      disseminated intravascular coagulation syndrome (DIC) occurring during the Gram
      negative septic shock is discussed.

PMID- 11581573
TI  - The p50-homodimer mechanism in tolerance to LPS.

PMID- 11581574
TI  - The expression of membrane-bound CD14 renders mouse B-1 cells susceptible to LPS.
AB  - The surface expression of CD14 on mouse B-1 cells and its role on their response
      to lipopolysaccharide (LPS) were studied by using the murine TH2.52 B-1 cell line
      and peritoneal B-1 cells. TH2.52 cells with the B-1 phenotype were found to
      express membrane-bound CD14. Furthermore, CD14 was expressed on physiological
      peritoneal CD5+ B-1 cells. The stimulation of CD14-expressing TH2.52 cells with a
      low concentration of LPS resulted in the activation of nuclear factor (NF)-B and
      a mitogen-activated protein kinase (MAPK). The LPS-induced NF-B and MAPK
      activation was markedly inhibited by anti-CD14 antibody. These results suggest
      that B-1 cells may respond to LPS via membrane-bound CD14.

PMID- 11581575
TI  - Decay-accelerating factor (DAF/CD55) is a functional active element of the LPS
      receptor complex.
AB  - Previously, we identified an 80 kDa membrane protein (LMP80) that is capable of
      binding to LPS and lipid A in the presence of LBP and sCD14. LMP80 could also be
      detected after immuno-coprecipitation of cell membranes with LPS and lipid A,
      indicating a physical contact of LMP80 and LPS/lipid A. Further analysis and
      peptide sequencing revealed that LMP80 is identical to CD55 (decay accelerating
      factor, DAF), a regulatory molecule of the complement cascade. Transfection of
      LPS-hyporesponsive Chinese hamster ovary (CHO) cells with human CD55 resulted in
      the translocation of NF-B upon stimulation with LPS or lipid A. Our results
      demonstrate a new functional role of CD55 as a molecule able to mediate LPS
      induced activation of cells that may be part of a multimeric LPS receptor
      complex.

PMID- 11581577
TI  - Signal integration in lipopolysaccharide (LPS)-stimulated murine macrophages.
AB  - Using a panel of LPS-inducible genes, selected for the capacity of their products
      to contribute to endotoxicity, normal macrophages were compared to macrophages
      deficient in CD14, CD11b/CD18, or TLR4 to elicit gene expression in response to
      Escherichia coli LPS or the LPS mimetic, Taxol. All genes were TLR4-dependent. At
      low doses of LPS or Taxol, all genes were also CD14-dependent; however, IP-10 and
      ICSBP remained poorly inducible even at much higher concentrations. A distinct
      subset of genes (COX-2, IL-12 p40, and IL-12 p35) was CD11b/CD18-dependent. NF-B
      translocation and MAPK phosphorylation were dysregulated in receptor-deficient
      macrophages. In contrast to E. coli LPS, a Porphyromonas gingivalis LPS
      preparation was found to be TLR2-, rather than TLR4-dependent, and resulted in
      differential expression of genes within the panel. These data suggest that: (i)
      TLR4 is necessary, but not sufficient, to induce the full repertoire of genes
      examined; (ii) CD14 and CD11b/CD18 facilitate signaling for induction of select
      subsets of genes that are also TLR4-dependent; and (iii) signaling through TLR2
      versus TLR4 differs quantitatively/qualitatively. These data support an LPS
      signaling complex on murine macrophages that minimally includes CD14, CD11b/CD18,
      and TLR4 to respond to E. coli LPS to elicit the full spectrum of gene
      expression.

PMID- 11581576
TI  - Involvement of TLR4/MD-2 complex in species-specific lipopolysaccharide-mimetic
      signal transduction by Taxol.
AB  - Taxol, an antitumor agent derived from a plant, mimics the action of
      lipopolysaccharide (LPS) in mice, but not in humans. The LPS-mimetic activity of
      Taxol is not observed in LPS-hyporesponsive C3H/HeJ mice which possess a point
      mutation in Toll-like receptor 4 (TLR4); therefore, TLR4 appears to be involved
      in both Taxol and LPS signaling. In addition, TLR4 was recently shown to
      physically associate with MD-2, a molecule that confers LPS-responsiveness on
      TLR4. Here we examined whether or not TLR4/MD-2 complex mediates a Taxol-induced
      signal by using transformants of the mouse pro-B cell line, Ba/F3, expressing
      mouse TLR4 alone, both mouse TLR4 and mouse MD-2, and both mouse MD-2 and mouse
      TLR4 lacking the cytoplasmic portion. Our results demonstrated that co-expression
      of mouse TLR4 and mouse MD-2 was required for Taxol responsiveness, and that the
      TLR4/MD-2 complex is the shared molecule in Taxol and LPS signal transduction in
      mice. We also found that mouse MD-2, but not human MD-2, is involved in Taxol
      signaling, suggesting that MD-2 is responsible for the species-specific
      responsiveness to Taxol.

PMID- 11581578
TI  - A K+ channel is involved in LPS signaling.
AB  - We previously showed a clear correlation between the molecular conformation of
      the lipid A moiety of endotoxin molecules and their cytokine-inducing capacity in
      mononuclear cells. While conically shaped lipid A moieties exhibit a high
      agonistic activity, a shift to a more cylindrically shaped lipid A leads to a
      decrease in agonistic and increase in antagonistic activity of the endotoxin
      molecules. Here, we show the involvement of a high-conductance Ca2+-activated
      potassium (MaxiK) channel in LPS signaling in macrophages. Corresponding to their
      biological activity, endotoxins activate a MaxiK channel as shown in outside-out
      patch-clamp experiments. LPS antagonists and anti-CD14 antibodies inhibit the LPS
      induced activation of the channel. Blocking of the channel by specific channel
      blockers in macrophage cultures leads to inhibition of cytokine mRNA production.
      In particular, this result implies that there is no other independent
      transmembrane signaling pathway operative in macrophages. A shift of the
      molecular conformation of an a priori antagonistic lipid A from a cylindrical to
      a conical shape by adding the membrane-active compound chlorpromazine increases
      the activity of the MaxiK channel and the biological activity of the lipid A. We
      conclude that the activation of the MaxiK channel is a very early step in LPS
      induced signaling in macrophages.

PMID- 11581579
TI  - Substituting for cerivastatin (Baycol).

PMID- 11581580
TI  - Oxycodone and oxycontin.

PMID- 11581581
TI  - Influenza prevention 2001-2002.

PMID- 11581582
TI  - Another long-acting methylphenidate (Metadate CD).

PMID- 11581583
TI  - Cord blood banks.

PMID- 11581585
TI  - Flood of health care legislation affects the home care industry.

PMID- 11581586
TI  - Home care, novels, and the future.

PMID- 11581587
TI  - Palliative care: hard choices.

PMID- 11581588
TI  - A day in the life of the home care pharmacist.

PMID- 11581589
TI  - A fall prevention program for the home environment.
AB  - Falls are the leading cause of injury, death, and disability among people older
      than 65. When elders fall, they sustain such injuries as hip, spine, hand, and/or
      pelvic fractures. The prognosis after such a fall is poor--only half of older
      adults hospitalized for hip fractures are able to return home or live
      independently again. Even without injury, falls cause a loss of confidence that
      results in reduced physical activity, increased dependency, and social
      withdrawal. As a home care agency dealing with a geriatric population, our goal
      was to develop a user-friendly fall prevention program that would promote
      multidisciplinary assessment and intervention. We have developed a preventive
      approach through which clinicians and patients can collaborate on preventing
      falls in the home and maintaining our patients' first priority: quality of life.

PMID- 11581590
TI  - Palliative care: a long-term solution for long-term care. Part 3: analgesic
      therapy.

PMID- 11581591
TI  - Cancer rehabilitation in the home care setting.

PMID- 11581592
TI  - Is it better on top? The triumph of supra-annular valves.

PMID- 11581593
TI  - Shedding light on denervation and transmyocardial laser revascularization.

PMID- 11581594
TI  - A morphologic study of Carpentier-Edwards pericardial xenografts in the mitral
      position exhibiting primary tissue failure in adults in comparison with Ionescu
      Shiley pericardial xenografts.
AB  - OBJECTIVE: We sought to investigate the durability and mechanism of the
      Carpentier-Edwards pericardial xenograft in the mitral position in comparison
      with that of the Ionescu-Shiley pericardial xenograft. METHODS: A total of 284
      patients who received the Ionescu-Shiley pericardial xenograft in the mitral
      position between 1980 and 1984 and 84 patients who received the Carpentier
      Edwards pericardial xenograft in the mitral position between 1984 and 1999 were
      included in the study. The freedom from reoperation rates for both graft types
      were determined. For morphologic study, the pathologic findings of 23 valves of
      123 explanted Ionescu-Shiley pericardial xenografts with structural valve
      deterioration, nonstructural valve deterioration, or both were determined and
      compared with those of 20 explanted Carpentier-Edwards pericardial xenografts
      with structural valve deterioration, nonstructural valve deterioration, or both.
      Each pathologic finding was graded and assigned a score. Both types were matched
      for age at reoperation (50-75 years) and duration of valve function (8-11 years).
      RESULTS: Freedom from reoperation caused by structural valve deterioration,
      nonstructural valve deterioration, or both was significantly better for
      Carpentier-Edwards pericardial xenografts than for Ionescu-Shiley pericardial
      xenografts at 8 years after the operation (Carpentier-Edwards pericardial
      xenografts: 91.3% vs Ionescu-Shiley pericardial xenografts: 71.9%, P =.0061), but
      it was similar for both types at 12 years (Carpentier-Edwards pericardial
      xenografts: 43.6% vs Ionescu-Shiley pericardial xenografts: 43.6%, P =.2865). No
      severe leaflet tears were seen among Carpentier-Edwards pericardial xenografts.
      The mean area percentage of tissue overgrowth was 15.3% in Carpentier-Edwards
      pericardial xenografts and 3.4% in Ionescu-Shiley pericardial xenografts (P
      =.0001). The mean calcification area percentage was 13.6% in Carpentier-Edwards
      pericardial xenografts and 31.5% in Ionescu-Shiley pericardial xenografts (P
      =.0001). CONCLUSIONS: Tissue overgrowth on the atrial surface, ventricular
      surface, or both was the cause of structural valve deterioration, nonstructural
      valve deterioration, or both of Carpentier-Edwards pericardial xenografts in
      adults. This was different from Ionescu-Shiley pericardial xenograft failure,
      which resulted from severe calcification and leaflet tears. Organized thrombi on
      cusps, in addition to valve design, may have contributed to such tissue
      overgrowth on Carpentier-Edwards pericardial xenografts.

PMID- 11581595
TI  - Operation for anorexigen-associated valvular heart disease.
AB  - OBJECTIVES: Recently, valvular regurgitation has been observed in patients who
      have taken fenfluramine or dexfenfluramine with or without phentermine. This
      study describes the clinical, echocardiographic, and pathologic findings of
      anorexigen-associated valvular heart disease and the surgical interventions
      required to treat it. METHODS: We reviewed clinical information on 14 patients
      with severe anorexigen-associated valvular disease who underwent cardiac
      operations. RESULTS: Thirteen women (mean age 44.2 +/- 5.3 years) received
      fenfluramine, 58.5 +/- 22.3 mg/day, and phentermine, 32.1 +/- 11.4 mg/day, for an
      average of 12.1 +/- 7.3 months before presentation. One woman received
      dexfenfluramine, 30 mg/day for 13 months, and phentermine, 60 mg/day,
      concomitantly for 6 months. Presenting symptoms included dyspnea (12 cases),
      palpitations (3), and atypical chest pain (3). Six patients had heart failure,
      and 4 had a new murmur. Echocardiography demonstrated severe mitral valve
      regurgitation in all patients. Seven also had aortic regurgitation, and 4 had
      significant tricuspid regurgitation. Four patients had successful mitral valve
      repair, 1 with concomitant aortic valve repair. Ten additional patients
      eventually required mitral valve replacement, 5 with concomitant aortic valve
      replacement. Excised valves demonstrated a glistening white appearance with
      plaque-like encasement of leaflets and chordae. Focal surface proliferation and
      fibrosis with a "stuck-on" appearance was consistently found. CONCLUSIONS:
      Anorexigen use may lead to severe multivalvular regurgitation with characteristic
      echocardiographic and pathologic findings. Recognition of drug-induced
      valvulopathy is important because of widespread use of these medications and the
      uncertain natural history of the disease. Early surgical experience suggests that
      valve repair is possible in these young patients.

PMID- 11581596
TI  - Three-dimensional geometric comparison of partial and complete flexible mitral
      annuloplasty rings.
AB  - BACKGROUND: It has previously been shown in sheep that mitral annular physiologic
      dynamics during the cardiac cycle are abolished by complete ring annuloplasty,
      but recent clinical studies suggest that flexible partial ring annuloplasty
      preserves normal mitral annular dynamics. METHODS: Eight radiopaque markers were
      sutured equidistantly around the mitral anulus in 3 groups of sheep: no-ring
      control animals (n = 16); animals with a flexible Tailor partial ring
      annuloplasty (n = 6; St Jude Medical, Inc, St Paul, Minn); and animals with a
      flexible Duran ring annuloplasty (n = 7; Medtronic, Inc, Minneapolis, Minn).
      After 7 to 10 days' recovery, 3-dimensional marker coordinates were measured by
      biplane cinefluoroscopy. Mitral annular area and folding (defined as displacement
      of the mitral anulus from a least-squares plane) and mitral annular septal
      lateral and commissure-commissure dimensions were calculated from the 3
      dimensional marker coordinates throughout the cardiac cycle every 17 ms. RESULTS:
      In the no-ring control group mitral annular area varied from 8.0 +/- 0.2 to 7.2
      +/- 0.2 cm(2) (10% +/- 2%), and the septal-lateral and commissure-commissure
      dimensions varied from 27.7 +/- 0.4 to 25.9 +/- 0.4 mm (7% +/- 1%) and from 38.2
      +/- 0.8 to 36.4 +/- 0.8 mm (5% +/- 1%), respectively (mean +/- standard error of
      the mean, P <.001 for all comparisons). In the Duran ring annuloplasty and Tailor
      partial ring annuloplasty groups, the anulus was fixed in size throughout the
      cardiac cycle (area = 4.8 +/- 0.1 and 5.3 +/- 0.3 cm(2), septal-lateral = 21.8 +/
      0.7 and 22.0 +/- 0.8 mm, and commissure-commissure = 27.7 +/- 0.7 and 31.2 +/-
      1.7 mm). Mitral annular folding did not differ significantly between the control
      and Tailor partial ring annuloplasty groups but was dampened in the Duran ring
      annuloplasty group. CONCLUSIONS: Partial Tailor flexible ring annuloplasty fixed
      mitral annular area and dimensions throughout the cardiac cycle in sheep;
      however, it preserved physiologic mitral annular folding dynamics, which might be
      important in terms of long-term valve function and prevention of left ventricular
      outflow tract obstruction.

PMID- 11581597
TI  - The double-orifice technique in mitral valve repair: a simple solution for
      complex problems.
AB  - OBJECTIVE: The aim of this study is to report our results with the central double
      orifice technique used for the treatment of complex mitral valve lesions.
      METHODS: The central double-orifice repair has been used in 260 patients (mean
      age, 56 +/- 14.3 years) over a period of 7 years. The mechanism responsible for
      mitral regurgitation was prolapse of both leaflets in 148 patients, prolapse of
      the anterior leaflet in 68, prolapse of the posterior leaflet with annular
      calcification or other unfavorable features in 31, and lack of leaflet coaptation
      for restricted motion or erosion of the free edge in 13. Degenerative disease was
      the cause of mitral regurgitation in 80.8% of the patients, rheumatic disease was
      the cause in 9.6%, endocarditis was the cause in 6.1%, and ischemic disease was
      the cause in 2.3%. RESULTS: Hospital mortality was 0.7%, and the overall survival
      at 5 years was 94.4% +/- 2.59%. Thirteen patients required a reoperation (2 early
      postoperatively and 11 late during the follow-up), for an overall freedom from
      reoperation of 90.0% +/- 3.37% at 5 years. Freedom from reoperation was lower in
      patients with rheumatic valve disease and in patients who did not undergo an
      annuloplasty procedure. CONCLUSIONS: The effectiveness and durability of the
      central double-orifice technique were assessed in this study. This type of repair
      can be a useful addition to the surgical armamentarium in mitral valve
      reconstruction.

PMID- 11581598
TI  - Surgical implications of variations in hand collateral circulation: anatomy
      revisited.
AB  - OBJECTIVES: One of the risks associated with harvesting the radial artery is hand
      ischemia. Accordingly, this study investigated the variations of the hand
      collateral circulation. METHODS: Fifty hands of cadavers were examined.
      Variations of the palmar arches were recorded. A classic superficial palmar arch
      was defined as direct continuity between the ulnar artery and the superficial
      palmar branch of the radial artery. A classic complete deep palmar arch was
      defined as direct continuity between the radial artery and the deep branch of the
      ulnar artery. RESULTS: A classic superficial palmar arch was found in 10% (5/50)
      of hands, and a classic complete deep palmar arch was found in 90% (45/50) of
      hands. The superficial palmar branch of the ulnar artery supplied blood to all
      fingers in 66% (33/50) of hands. Although the superficial palmar branch of the
      ulnar artery was continuous with the radial artery in only 34% (17/50) of hands
      (including the classic type of superficial palmar arch), every hand had at least
      one major branch connecting the radial and ulnar arteries. CONCLUSIONS:
      Variations in the terminations of the radial and ulnar arteries are common.
      Although the classic type of superficial palmar arch occurs relatively
      infrequently, there is always a significant anastomosis between the radial and
      the ulnar artery in the hand. This anatomic study confirms the presence of a
      collateral supply in the hand. In the absence of vascular disease, harvesting the
      radial artery should be regarded as a safe procedure.

PMID- 11581599
TI  - Composite lengthened arterial conduits: long-term angiographic results of an
      uncommon surgical strategy.
AB  - BACKGROUND: We sought to evaluate the long-term patency rate of composite
      lengthened conduits. METHODS AND RESULTS: From December 1991 to April 2000, 43
      patients had a composite lengthened arterial conduit. There was a mean of 2.83 +/
      1.23 anastomoses per patient. No 30-day mortality occurred. Five patients died
      from 3 to 84 months after the operation (mean, 38.6 +/- 34.6 months). After a
      mean follow-up of 57.0 +/- 32.3 months (range, 3-99 months), all the survivors
      are asymptomatic. The only cardiac major events recorded were 2 (4.6%) late acute
      myocardial infarctions in the patients who died. Eight-year survival and event
      free survival were both 80.4% +/- 9.1% (range, 3%-93%). In the early period (13.5
      +/- 4.8 days) in 26 patients, 26 arterial composite lengthened conduits and 37
      distal anastomoses had postoperative angiographic control; all the anastomoses
      were rates as grade A, according to Fitzgibbon classification. In the late period
      (29 +/- 30 months) in 23 patients, 23 arterial composite lengthened conduits and
      34 distal anastomoses were checked; the patency rate was 22 (95.6%) of 23 for the
      composite lengthened conduits and 33 (97%) of 34 for the distal anastomoses.
      CONCLUSIONS: In particular situations, when the length of an arterial conduit is
      not enough to allow a correct use of the graft, lengthening of an arterial
      conduit can be a safe and effective technique.

PMID- 11581601
TI  - The coronary delivery of marrow stromal cells for myocardial regeneration:
      pathophysiologic and therapeutic implications.
AB  - OBJECTIVES: Bone marrow stromal cells contain "adult stem cells." We tested the
      hypothesis that coronary-infused bone marrow stromal cells may populate the
      infarcted heart and undergo milieu-dependent differentiation to regenerate
      functional tissues with different phenotypic features. METHODS: Isogenic adult
      rats were used as donors and recipients to simulate autologous transplantation
      clinically. Myocardial infarction was created by proximal occlusion of left
      coronary artery in 12 recipient rats. Isolated bone marrow stromal cells were
      purified, expanded, and retrovirally transduced with LacZ reporter gene for cell
      labeling. Stromal cells were then infused into the briefly distally clamped
      ascending aorta of recipient rats 2 weeks after left coronary artery ligation.
      The hearts were harvested immediately (n = 2) or 4 weeks (n = 10) later to trace
      the implanted cells and identify their phenotypes. RESULTS: Viable cells labeled
      with LacZ reporter gene were identified in 8 recipient hearts. Immediately after
      cell infusion, the labeled cells were trapped within the coronary capillaries.
      After 4 weeks, they could be detected individually or in clusters within
      myocardial scar expressing fibroblastic phenotype or outside the infarction area
      with morphologic features of normal cardiomyocytes. Some were incorporated into
      endocardium and capillary endothelium. CONCLUSIONS: Our findings suggest that
      bone marrow stromal cells can traffic through the coronary system to the injured
      heart and form cardiomyocytes or fibroblasts, depending on the specific
      microenvironment. Endothelial progenitor cells in the stromal cell population may
      be involved in the postinfarction neovascularization process. Whether therapeutic
      use of bone marrow stromal cells can improve the myocardial healing and
      remodeling process after infarction is worthy of further investigation.

PMID- 11581600
TI  - Clinical evaluation of St Jude Medical Hemodynamic Plus versus standard aortic
      valve prostheses: The Italian multicenter, prospective, randomized study.
AB  - OBJECTIVE: Hemodynamic and clinical performances of 21-mm and 23-mm St Jude
      Medical Hemodynamic Plus aortic valves (St Jude Medical, Inc, St Paul, Minn) were
      compared with those of 21-mm and 23-mm St Jude Medical standard cuff aortic
      valves in the first such multicenter, prospective, randomized study. Hemodynamic
      Plus valves are mechanical, bileaflet prostheses suitable for the small aortic
      anulus. METHODS: Patients with 21-mm and 23-mm anulus diameters were randomized
      to receive either a Hemodynamic Plus or a standard cuff valve. Postoperatively
      and at 6 months after the operation, patients underwent 2-dimensional Doppler
      echocardiography. Ejection fraction, cardiac output, peak gradient, mean
      gradient, effective orifice area, effective area index, and performance index
      were calculated. Postoperative and 6-month echocardiographic measurements and
      their variations across observation times were analyzed statistically. RESULTS:
      Of the 140 patients enrolled, 5 died at operation and 1 died of aortic dissection
      during the follow-up period. Eight patients were lost to follow-up. A total of
      125 patients completed the study. In 1 patient a sewing cuff escaped
      intraoperatively. At 6 months the 21-mm and 23-mm Hemodynamic Plus valves showed
      significantly lower peak gradients and mean gradients than those of the 21-mm and
      23-mm standard cuff valves. The 21-mm Hemodynamic Plus valves had gradients
      similar to those of the 23-mm Hemodynamic Plus valves. The effective orifice area
      did not differ significantly between the Hemodynamic Plus and standard cuff
      valves at either measurement. No valve mismatch was found in the 4 groups of
      patients. A more enhanced decrease of peak gradients and mean gradients and a
      more enhanced increase of effective orifice areas, effective area indices, and
      performance indices were found across observation times for patients with
      Hemodynamic Plus valves compared with those with standard cuff valves.
      CONCLUSIONS: Clinical hemodynamic performances of 21-mm and 23-mm St Jude Medical
      Hemodynamic Plus valves correspond closely with those of standard cuff valves,
      and gradients are substantially better than those of standard cuff valves of the
      same diameter. Therefore, use of this valve may minimize the need for aortic
      anulus enlargement. Early follow-up results with the Hemodynamic Plus valves were
      excellent, although more time is required to confirm this outcome.

PMID- 11581602
TI  - Collagen synthesis and collagenase activity of cryopreserved heart valves.
AB  - OBJECTIVE: Durability of the valve seems to be dependent on the remodeling
      ability of the valve itself, which is controlled by both collagen synthesis and
      collagenolytic activity of valvular fibroblasts and endothelial cells. However,
      the balance of collagen synthesis and collagenolysis of the cryopreserved valve
      has not yet been clearly revealed. Thus, we assessed the collagen synthesis and
      collagenolysis ability of the cryopreserved valve. METHODS: Twelve valves were
      divided into 2 groups: freshly harvested valves (n = 6) and cryopreserved valves
      (n = 6). We measured the collagen content using Sirius red, a dye selective to
      the collagen. Collagen synthesis was evaluated by means of the tritiated proline
      incorporation method. Noncollagenase-digestible counts, which represent protein
      synthesis, and collagenase-digestible counts, which represent collagen synthesis,
      were estimated. Collagenase activity of the valves was assessed by gelatin
      zymography. RESULTS: The collagen content of the cryopreserved group was
      maintained. The noncollagenase-digestible counts of the cryopreserved group
      decreased from 3862 +/- 1180 counts/mg to 1174 +/- 1362 counts/mg, and the
      collagenase-digestible counts of the cryopreserved group were 831 +/- 762
      counts/mg compared with the value of 1062 +/- 136 counts/mg for the freshly
      harvested group. The collagenase activity of the cryopreserved group was observed
      at the same level as that of the freshly harvested group, despite the serious
      endothelial damage of the cryopreserved valves. CONCLUSIONS: Although the
      collagen synthesis of cryopreserved valves was relatively maintained, the protein
      synthesis was highly diminished, and the collagenolysis ability was activated
      immediately after the thawing process. These results imply that the
      cryopreservation procedure itself may cause the collagen metabolism to be on the
      degradable side, which will lead to valve failure.

PMID- 11581603
TI  - Cardiac nociceptive reflexes after transmyocardial laser revascularization:
      implications for the neural hypothesis of angina relief.
AB  - OBJECTIVE: The mechanism by which transmyocardial laser revascularization
      relieves angina is not understood. One theory is that laser-induced thermal
      damage to cardiac nerves results in cardiac denervation. This study examined the
      acute effects of transmyocardial laser revascularization on reflex responses
      mediated by cardiac nociceptors, the left ventricular receptors with sympathetic
      afferent fibers that are thought to mediate anginal chest pain. METHODS:
      Experiments were performed in 13 chloralose-anesthetized dogs with sinoaortic
      denervation and vagotomy. Left ventricular receptors with sympathetic afferent
      fibers were activated by epicardial and intracoronary bradykinin before and 45
      minutes after transmyocardial laser revascularization. Reflex responses elicited
      by bradykinin were quantitated by direct recording of efferent renal sympathetic
      nerve activity. Transmyocardial laser revascularization was performed in the open
      chest model with a hand-held holmium:YAG laser (2.1-microm wavelength). RESULTS:
      An average of 44.5 +/- 1.0 channels were created. Before transmyocardial laser
      revascularization, reflex increases in renal sympathetic nerve activity were
      elicited by both epicardial and intracoronary bradykinin. After transmyocardial
      laser revascularization, there was no significant attenuation in the reflex
      responses to either epicardial (before, 66% +/- 8%; after, 100% +/- 24%; P =.19)
      or intracoronary (before, 124% +/- 37%; after, 108% +/- 25%; P =.44) bradykinin.
      CONCLUSIONS: Transmyocardial laser revascularization has no significant short
      term effect on reflexes mediated by left ventricular receptors with sympathetic
      afferent fibers in anesthetized dogs. These results indicate that transmyocardial
      laser revascularization does not acutely interrupt the afferent nerves, which are
      believed to transmit the perception of anginal pain.

PMID- 11581604
TI  - Nuclear factor-kappa B decoy attenuates neuronal damage after global brain
      ischemia: a future strategy for brain protection during circulatory arrest.
AB  - OBJECTIVES: Recent studies have reported that cis element decoy
      oligodeoxynucleotides against nuclear factor-kappa B block the activation of
      genes that mediate ischemic injury. To improve brain protection during
      circulatory arrest in cardiac surgery, we evaluated the efficacy of nuclear
      factor-kappa B decoy oligodeoxynucleotides in preventing neuronal damage after
      global brain ischemia. METHODS: Hemagglutinating virus of Japan-liposome complex
      with fluorescein isothiocyanate-labeled nuclear factor-kappa B decoy
      oligodeoxynucleotides was injected through the carotid artery during 20 minutes
      of global brain ischemia in rats to evaluate the efficacy of transfecting the
      decoy oligodeoxynucleotides. The messenger RNA levels of several factors related
      to ischemia-reperfusion injury in the hippocampus were estimated by a real-time
      polymerase chain reaction method 1 hour after reperfusion. Neuronal damage was
      evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick end labeling staining and by using immunohistochemical study of
      microtubule-associated protein 2 in the hippocampus CA-1 region 7 days after
      ischemia. RESULTS: Introduction of the nuclear factor-kappa B decoy
      oligodeoxynucleotides into rat brain neurons through the carotid artery during
      global brain ischemia was markedly successful. The polymerase chain reaction
      study showed that the transfected nuclear factor-kappa B decoy
      oligodeoxynucleotides effectively inhibited the expression of tumor necrosis
      factor alpha interleukin 1 beta and intracellular adhesion molecule 1 messenger
      RNA 1 hour after global brain ischemia. Terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick end labeling staining and microtubule
      associated protein 2 immunohistochemistry showed that the transfected nuclear
      factor-kappa B decoy oligodeoxynucleotides significantly attenuated the neuronal
      damage 7 days after global brain ischemia. CONCLUSIONS: Therapeutic transfection
      of nuclear factor-kappa B decoy oligodeoxynucleotides during brain ischemia may
      be useful for attenuating neuronal damage, suggesting a strategy for cerebral
      protection against global ischemia.

PMID- 11581605
TI  - The adenosine triphosphate-sensitive potassium channel opener nicorandil protects
      the ischemic rabbit spinal cord.
AB  - OBJECTIVE: We investigated the protective effects of an adenosine triphosphate
      sensitive potassium channel opener nicorandil in the rabbit model of spinal cord
      ischemia. METHODS: Rabbits were randomized into 4 groups (each n = 6): the
      nicorandil group (100 microg/kg intravenous nicorandil 10 minutes before
      ischemia); the glibenclamide plus nicorandil group (3 mg/kg intravenous
      glibenclamide, an antagonist of adenosine triphosphate-sensitive potassium
      channels, 10 minutes before nicorandil administration); the vehicle group
      (vehicle alone); and the sham operation group (without spinal cord ischemia).
      Spinal cord ischemia was induced by balloon occlusion of the infrarenal abdominal
      aorta for 15 minutes at 39 degrees C. Neurologic function was graded into
      Johnson's score at 8 hours, 1 day, and 2 days. Histopathologic examination was
      performed at 2 days, and the number of intact motor neuron cells was compared.
      RESULTS: Johnson scores of the glibenclamide plus nicorandil and vehicle groups
      were significantly lower than those of the sham operation and nicorandil groups
      at each time point, and no statistically significant difference was observed
      between the glibenclamide plus nicorandil and vehicle groups. Histopathologic
      examination revealed that motor neurons were almost normal in the nicorandil
      group, whereas about 55% of motor neurons were lost in the vehicle and
      glibenclamide plus nicorandil groups. CONCLUSIONS: Nicorandil has a protective
      effect on the ischemic rabbit spinal cord, and the beneficial effect seems
      mediated through the activation of adenosine triphosphate-sensitive potassium
      channels.

PMID- 11581606
TI  - Experimental study on the effect of antegrade cerebral perfusion on brains with
      old cerebral infarction.
AB  - OBJECTIVE: Patients with old cerebral infarction who undergo aortic arch
      operations are susceptible to postoperative neurologic dysfunction. To verify
      such susceptibility, we performed this experimental study. METHODS: A cerebral
      infarct model was created in mongrel dogs by means of injection of cylindrical
      silicone embolus through the internal carotid artery. The dogs that had obvious
      neurologic deficits 1 day later and survived for 4 weeks or more were included in
      the cerebral infarct model. One month after cerebral infarction was induced, deep
      hypothermia and selective cerebral perfusion were used in 14 mongrel dogs
      (infarct group, n = 7; control group, n = 7). During this procedure, serum
      glutamate concentration and venous-arterial lactate difference were measured.
      Histopathologic study of the brain was also performed. RESULTS: Changes in venous
      arterial lactate difference in both groups were almost similar, except in the
      rewarming phase. At 32 degrees C during rewarming, the venous-arterial lactate
      difference in the infarct group was significantly higher than that in the control
      group (P =.006). Although pre-cooling concentrations of serum glutamate were
      similar in both groups, the values in the infarct group at the end of rewarming
      were significantly higher than those in the control group (P =.046). On
      histologic examination, the presence of old cerebral infarction with gliosis was
      confirmed in the infarct group, but neither new cerebral infarction nor
      destruction of the blood-brain barrier was found. CONCLUSION: We observed an
      accelerated anaerobic metabolism and an increased extracellular glutamate release
      in the infarct group. The brain with old cerebral infarction is more susceptible
      to ischemia during arch operation than noninfarcted brain.

PMID- 11581607
TI  - Recombinant human erythropoietin administration in cardiac surgery.
AB  - OBJECTIVE: Postoperative anemia and multiple blood transfusions are still
      important problems in cardiac surgery. During the past few years, there have been
      some reports indicating that multiple recombinant human erythropoietin infusions
      starting at least 2 weeks before the operation induced erythropoiesis. We aimed
      to reduce the risk of adverse reactions of high doses of recombinant human
      erythropoietin and reduce the period of hospitalization by using it only once, 4
      days before the operation. METHODS: Twenty-five patients received recombinant
      human erythropoietin 4 days before the operation, and 28 patients comprised the
      control group. All the hematologic parameters of the patients are measured on the
      day of admission, the day before the operation (fourth day), the first day after
      the operation, and 1 week later. RESULTS: In the recombinant human erythropoietin
      group the mean hemoglobin concentration increased on the morning of the operation
      (14.5 +/- 0.52 g/dL in the recombinant human erythropoietin group and 12.4 +/-
      0.65 in the control group, P <.05). To maintain hemoglobin levels at greater than
      8.5 g/dL, 330 +/- 33 mL of homologous transfusion was required in the recombinant
      human erythropoietin group, whereas 680 +/- 75 mL was required in the control
      group (P <.01). CONCLUSION: Recombinant human erythropoietin induces
      erythropoiesis rapidly, even when it is used with a low single dose just 4 days
      before the operation. No adverse reactions were seen with this kind of
      recombinant human erythropoietin treatment.

PMID- 11581608
TI  - Cardiac surgery increases the activity of matrix metalloproteinases and nitric
      oxide synthase in human hearts.
AB  - OBJECTIVES: Heart function is variably impaired after cardiopulmonary bypass. We
      hypothesized that, similar to other myocardial injury states, cardiopulmonary
      bypass leads to enhanced activity of nitric oxide synthase and matrix
      metalloproteinases. METHODS: We obtained right atrial biopsy specimens and plasma
      samples at the onset and termination of cardiopulmonary bypass in 10 patients.
      Biopsy specimens were analyzed for nitric oxide synthase activity by using a
      citrulline assay, whereas plasma and tissue were analyzed for matrix
      metalloproteinase-9 and matrix metalloproteinase-2 activity by using zymography.
      Tissue inhibitor of metalloproteinase-4 was analyzed by means of Western
      blotting. The cellular expression of inducible nitric oxide, endothelial nitric
      oxide synthase, matrix metalloproteinase-2, and matrix metalloproteinase-9 was
      determined in right atrial biopsy samples from 3 additional patients by using the
      appropriate conjugated antibodies. RESULTS: Nitric oxide synthase activity
      increased from the beginning to the end of bypass (4.46 +/- 1.07 vs 16.77 +/-
      4.86 pmol citrulline/mg of protein per minute, respectively; P =.018). Pro-matrix
      metalloproteinase-9 activity increased in hearts (199 +/- 41 vs 660 +/- 177
      density units/mg protein; P =.008) and plasma (14.1 +/- 4.6 vs 52.2 +/- 5.9
      density units/mg protein; P =.008). Pro-matrix metalloproteinase-2 activity
      increased in the heart (201 +/- 23 vs 310 +/- 35 density units/mg protein, P
      <.05) but not in plasma. Tissue inhibitor of metalloproteinase-4 expression in
      the heart decreased (1574 +/- 280 vs 864 +/- 153 density units, P =.014).
      CONCLUSIONS: Cardiopulmonary bypass activates enzymes mediating acute
      inflammation and organ injury (ie, nitric oxide synthase, matrix
      metalloproteinase-9, and matrix metalloproteinase-2). Decreased tissue inhibitor
      of metalloproteinase-4 expression allows relatively unopposed increases in matrix
      metalloproteinase tissue activity. We postulate that these changes play a role in
      the pathogenesis of heart dysfunction after bypass surgery.

PMID- 11581609
TI  - Is hyperglycemia seen in children during cardiopulmonary bypass a result of
      hyperoxia?
AB  - OBJECTIVE: We sought to identify whether elevated PaO (2) itself can directly
      cause hyperglycemia in newborns and to document any additional effects of
      cardiopulmonary bypass on this response. METHODS: Piglets were exposed to either
      normoxia (88 +/- 6 mm Hg) or hyperoxia (470 +/- 28 mm Hg) in the following
      studies. Anesthetized 3-day-old neonatal pigs were either ventilated for 2 hours
      of normoxia (n = 5) or hyperoxia (n = 5) or placed on normothermic, normoxic
      cardiopulmonary bypass (n = 6) and then randomly assigned to either undergo a 2
      hour normoxic period or a 1-hour hyperoxic episode, followed by a return to
      normoxia for an additional hour. Blood glucose levels were measured in all
      animals. RESULTS: No significant changes were observed in blood glucose levels in
      neonatal pigs that underwent 2 hours of normoxic ventilation (5.0 +/- 0.6 mmol/L)
      or cardiopulmonary bypass (6.6 +/- 1.6 mmol/L). However, the ventilatory model
      showed a significant and sustained (P <.001) hyperglycemic response after both 1
      hour (8.6 +/- 1.0 mmol/L) and 2 hours (9.8 +/- 1.6 mmol/L) of hyperoxia. In the
      cardiopulmonary bypass model, exposure to 1 hour of hyperoxia elicited a
      significant (P <.05) hyperglycemic response (10.3 +/- 1.2 mmol/L), followed by a
      return to normal blood glucose levels (6.6 +/- 1.6 mmol/L) with a return to
      normoxia. This hyperoxia-mediated hyperglycemic response was confirmed when data
      examined from children undergoing cardiopulmonary bypass for primary repair of
      their congenital defects also identified a significant positive correlation (r =
      0.72, P =.02) between oxygen levels and blood glucose levels measured before and
      at the end of cardiopulmonary bypass. CONCLUSIONS: Hyperoxia triggers a
      hyperglycemic response in both ventilatory and bypass models. Cardiopulmonary
      bypass does not exacerbate this response, as shown by the similar levels of
      hyperglycemia sustained for the duration of the hyperoxic exposure in both
      experimental models. Therefore, not only may hyperoxia play a crucial role in the
      hyperglycemic response seen during neonatal cardiopulmonary bypass, but its
      effect on glucose homeostasis should be considered whenever children are exposed
      to hyperoxia.

PMID- 11581610
TI  - Overexpression of connexin 43 in skeletal myoblasts: Relevance to cell
      transplantation to the heart.
AB  - OBJECTIVE: Skeletal myoblast transplantation is a promising strategy for treating
      end-stage heart failure. One potential problem in the development of functional,
      synchronously contracting grafts is the degree of intercellular communication
      between grafted myoblasts and host cardiomyocytes. Thus it is expected that
      enhancement of intercellular gap junction formation would result in improved
      efficiency of skeletal myoblast transplantation. In this study we investigated
      whether myoblasts overexpressing connexin 43, a major cardiac gap junction
      protein, would enhance this intercellular communication. METHODS AND RESULTS: L6
      rat skeletal myoblast cell lines overexpressing connexin 43 were generated by
      means of gene transfection and clonal selection. Connexin 43 overexpression of
      these myoblasts, which continued both in undifferentiated and differentiated
      states (up to 17-fold greater protein level in comparison with control
      transfected myoblasts, as measured with Western blotting), was observed on cell
      surfaces where gap junctions should exist. Both dye microinjection and scrape
      loading with fluorescent dyes showed enhancement in intercellular dye transfer
      between connexin 43-transfected myoblasts compared with that found in control
      transfected cells. Morphologically, these myoblasts fused and differentiated into
      multinucleated myotubes more rapidly, demonstrating a higher level of cellular
      creatine kinase activity as a marker of myogenic differentiation throughout the
      culture period compared with that of control-transfected myoblasts. CONCLUSIONS:
      We have generated connexin 43-overexpressing skeletal myoblast cell lines that
      resulted in improved formation of functional intercellular gap junctions, which
      could be relevant to synchronous contraction of grafted myoblasts in the heart.
      In addition, these cells demonstrated more rapid differentiation, which would
      also be advantageous in a graft for transplantation to the heart.

PMID- 11581611
TI  - Influence of clenbuterol treatment during six weeks of chronic right ventricular
      pressure overload as studied with pressure-volume analysis.
AB  - OBJECTIVES: Chronic pressure overload cardiac hypertrophy produces ventricular
      dysfunction. There is evidence that clenbuterol, a beta(2)-adrenoceptor agonist,
      produces cardiac hypertrophy with preserved function in rodents. We sought to
      determine the cardiac hypertrophic effects of clenbuterol on the thin-walled
      ventricles of large animals undergoing chronic pressure overload by means of
      pulmonary artery banding. METHODS: Right ventricular pressure-volume loops were
      obtained in open-chest sheep before and after 6-1/2 weeks of pulmonary artery
      banding by using micromanometer conductance catheters. Animals were randomly
      assigned to treatment with either saline solution (n = 7) or clenbuterol (n = 8).
      Treatment was started immediately after pulmonary artery banding. RESULTS: Acute
      pulmonary artery banding increased the right ventricular systolic pressure
      equally in both groups (saline group, 23.9 +/- 3.3 to 48.1 +/- 9.7 mm Hg;
      clenbuterol group, 24.3 +/- 2.8 to 48.6 +/- 10.7 mm Hg [mean +/- standard
      deviation]). Six weeks of treatment produced no significant differences in the
      body weight, heart weight, heart/body weight ratio, right ventricular wall
      thickness, heart rate, and stroke volume between the groups. However, the slope
      of the end-systolic pressure-volume relation and the slope of the first
      derivative of the right ventricular developed pressure/end-diastolic volume
      relation were significantly increased when compared with baseline values in
      clenbuterol-treated animals but not in saline-treated animals. CONCLUSION:
      Clenbuterol treatment during pulmonary artery banding improves systolic function
      of the chronically pressure-overloaded right ventricle. This has important
      implications for the use of pharmacologic agents in modulating cardiac
      adaptation.

PMID- 11581612
TI  - Left ventricular volume reduction surgery for heart failure: a physiologic
      perspective.
AB  - BACKGROUND: Ventricular volume reduction surgery for idiopathic cardiomyopathy
      fails to improve cardiac output and is associated with a high incidence of
      recurrent heart failure. Volume reduction surgery achieved by removing akinetic
      or dyskinetic myocardium after myocardial infarction appears to be associated
      with better outcomes. The reasons for the differences in outcomes are not clear.
      METHODS AND RESULTS: The hemodynamic effect of the major forms of volume
      reduction surgery were predicted by using a composite model of the left ventricle
      in which 20% of the myocardium was given properties of either weak but
      contracting muscle, an akinetic scar, or a dyskinetic scar (aneurysm). The end
      systolic and end-diastolic pressure-volume relationships were determined
      numerically for each simulated operation. Any volume reduction procedure reduced
      chamber size, shifting end-systolic and end-diastolic pressure-volume
      relationships leftward. With resection of weak but contracting muscle, the
      leftward shift was greater for the end-diastolic than for the end-systolic
      pressure-volume relationship. Conversely, with resection of dyskinetic scar, the
      leftward shift was greater for end-systolic than for end-diastolic pressure
      volume relationships. In contrast, resection of stiff scar shifted the 2
      relationships equally. The effect on overall pump function was indexed by the
      relationship between total ventricular mechanical work and end-diastolic
      pressure. There was a beneficial effect on this relationship of resecting
      dyskinetic tissue, an equivocal effect of akinetic scar resection, and a negative
      effect of removing contracting myocardium. CONCLUSIONS: The effect of volume
      reduction surgery on overall ventricular pumping characteristics is determined by
      the differential effects on end-systolic and end-diastolic properties, which in
      turn are determined by the material properties of the region being removed.

PMID- 11581613
TI  - Thoracoscopic thymomectomy with the da Vinci computer-enhanced surgical system.

PMID- 11581614
TI  - Circulatory support with a direct cardiac compression device: a less invasive
      approach with the AbioBooster device.

PMID- 11581615
TI  - A phase II trial of surgical resection and adjuvant high-dose hemithoracic
      radiation for malignant pleural mesothelioma.
AB  - BACKGROUND: Surgical resection of malignant pleural mesothelioma is reported to
      have up to an 80% rate of local recurrence. We performed a phase II trial of high
      dose hemithoracic radiation after complete resection to determine feasibility and
      to estimate rates of local recurrence and survival. METHODS: Patients were
      eligible if they had a resectable tumor, as determined by computed tomographic
      scanning, and adequate cardiopulmonary function for extrapleural pneumonectomy or
      pleurectomy/decortication. After complete resection, patients received
      hemithoracic radiation (54 Gy) and then were followed up with serial computed
      tomographic scanning. RESULTS: From 1995 to 1998, 88 patients (73 men and 15
      women; median age, 62.5 years) were entered into the study. The operations
      performed included 62 extrapleural pneumonectomies (70%) and 5
      pleurectomies/decortications; procedures for exploration only were performed in
      21 patients. Seven (7.9%) patients died postoperatively. Adjuvant radiation
      administered to 57 patients (54 undergoing extrapleural pneumonectomy and 3
      undergoing pleurectomy/decortication) at a median dose of 54 Gy was well
      tolerated (grade 0-2 fatigue, esophagitis), except for one late esophageal
      fistula. The median survival was 33.8 months for stage I and II tumors but only
      10 months for stage III and IV tumors (P =.04). For the patients undergoing
      extrapleural pneumonectomy, the sites of recurrence were locoregional in 2,
      locoregional and distant in 5, and distant only in 30. CONCLUSION: Hemithoracic
      radiation after complete surgical resection at a dose not previously reported is
      feasible. This approach dramatically reduces local recurrence and is associated
      with prolonged survival for early-stage tumors. Stage III disease has a high risk
      of early distant relapse and should be considered for trials of systemic therapy
      added to this regimen of resection and radiation.

PMID- 11581616
TI  - Benefit of surgery after chemoradiotherapy in stage IIIB (T4 and/or N3) non-small
      cell lung cancer.
AB  - OBJECTIVE: The purpose of this study was to evaluate postchemoradiotherapy
      surgery in stage IIIB non-small cell lung cancer. METHODS: Forty patients with
      stage IIIB non-small cell lung cancer were included in this phase II study. A
      preoperative diagnosis of stage IIIB cancer was based on mediastinoscopy or a
      thoracotomy in all patients. Induction treatment included two cycles of cisplatin
      (100 mg/m(2), day 1), 5-fluorouracil (1 g/m(2), days 1-3), and vinblastine (4
      mg/m(2), day 1) combined with 42 Gy of hyperfractionated radiotherapy delivering
      21 Gy in two sessions. Patients with a clinical response were offered surgery.
      RESULTS: The minimum follow-up for survivors was 48 months. Thirty patients had a
      T4 lesion and 18 had N3 disease. Twenty-nine patients (73%) had a clinical
      objective tumor response after induction treatment. These 29 patients underwent
      thoracotomy, and a complete resection was performed in 23 (58%). Two
      postoperative deaths occurred (7%). Four patients had a pathologic complete
      response at the time of surgery (10%). The 5-year survival is 19% for the overall
      population. When only patients who had persistent viable tumor cells at surgery
      are considered (n = 25), the 5-year survival is 28%. The 5-year survival is 42%
      for patients having no mediastinal lymph node involvement at the time of surgery
      and being treated with complete resection. CONCLUSION: This study shows that
      surgery, when feasible, is associated with a 28% long-term survival for patients
      in whom chemoradiotherapy alone fails to control disease.

PMID- 11581617
TI  - Completely resected stage IIIA non-small cell lung cancer: the significance of
      primary tumor location and N2 station.
AB  - BACKGROUND: The number of N2 stations (single vs multiple N2 stations) is an
      important prognostic factor in patients with completely resected stage IIIA-N2
      non-small cell lung cancer. However, the significance of both the N2 station(s)
      actually involved and the primary tumor location remains unclear. METHODS: The
      database was built with the use of a questionnaire survey on the survival of
      patients with pathologic stage IIIA-N2 non-small cell lung cancer completely
      resected between January 1992 and December 1993. The survey was performed by the
      Japan Clinical Oncology Group as of July 1999. The data include information on
      the survival and N2 stations of 402 patients. RESULTS: A frequently metastasized
      single N2 station was the lower pretracheal station in primary tumors in the
      right upper lobe, the subaortic station in the left upper lobe, and the
      subcarinal station in the right middle or lower lobe and the left lower lobe. In
      multiple N2 stations, the frequency of metastasis of the N2 station observed in a
      single N2 station was as high as 72% to 89%, and one or two other frequently
      metastasized stations were added to each group. Regarding the survival of
      patients with a primary tumor in each lobe except for the left lower lobe, a
      single N2 station resulted in a significantly better survival than did multiple
      N2 stations. Furthermore, the overall survivals classified according to each
      primary site showed a significant difference among the four primary sites (P
      =.04). CONCLUSIONS: The primary tumors in each lobe showed a prevalence of N2
      station(s). The number of N2 stations is a good prognosticator except in patients
      with a primary tumor in the left lower lobe. In addition, the site of a primary
      tumor itself is also considered to influence the survival of the patients.

PMID- 11581618
TI  - Malignant transformation of the esophageal mucosa is enhanced in p27 knockout
      mice.
AB  - OBJECTIVE: In a previous study, we showed that experimentally induced
      gastroduodenal-esophageal reflux in mice treated with a carcinogen can result in
      Barrett esophagus and Barrett-associated adenocarcinoma. Since we have shown that
      most Barrett-associated adenocarcinomas in human beings have lost the tumor
      suppressor gene p27, we sought to determine whether cancer would be more likely
      to develop in p27 knockout mice than in p27 heterozygous or p27 wild type mice.
      METHODS: Three groups of mice were treated by esophagojejunostomy resulting in
      gastroduodenal-esophageal reflux and by a carcinogen (N -methyl-N 
      benzylnitrosamine): group I (50 wild type), group II (45 p27 heterozygous), and
      group III (50 p27 knockout). The mice were killed 18 to 20 weeks after operation
      and studied macroscopically and histopathologically. RESULTS: Barrett esophagus
      developed in 7 (14%) mice in group I, 4 (8.9%) mice in group II, and 13 (26%)
      mice in group III. Cancers developed in 30 (60%) mice in group I, 31 (68%) mice
      in group II, and 43 (86%) mice in group III. Ten percent of the cancers in group
      I were adenocarcinomas, as were 16.1% in group II, and 23.3% in group III. The
      difference between rates of Barrett esophagus in groups I and II compared with
      group III was statistically significant (P =.035), as was true of the cancer
      rates (P =.006). The percentage of cancers that were adenocarcinomas was highest
      in group III, but not significantly different from groups I and II. CONCLUSIONS:
      This experimental mouse model of Barrett esophagus and Barrett- associated
      adenocarcinoma is similar to what occurs in human beings and may be useful in
      developing methods to inhibit malignant transformation of Barrett esophagus.

PMID- 11581619
TI  - Complete excision of secondary chordae of the anterior mitral leaflet as an
      adjunct in surgical management of hypertrophic obstructive cardiomyopathy in
      pediatric patients.

PMID- 11581620
TI  - Living-donor lobar lung transplantation for primary pulmonary hypertension in an
      adult.

PMID- 11581621
TI  - Extracorporeal membrane oxygenation for graft failure after heart
      transplantation: recent Vienna experience.

PMID- 11581622
TI  - Reduced exercise capacity is associated with reduced nitric oxide production
      after heart transplantation.

PMID- 11581623
TI  - Reversal of severe vasoplegia with single-dose methylene blue after heart
      transplantation.

PMID- 11581624
TI  - Thymolipomas in association with myasthenia gravis.

PMID- 11581625
TI  - Comparison of six pediatric cardiopulmonary bypass pumps during pulsatile and
      nonpulsatile perfusion.

PMID- 11581626
TI  - Shrinkage of excluded aneurysmal spaces: the excellent results of endovascular
      stent grafting through the aortic arch for distal arch aneurysm.

PMID- 11581627
TI  - Critical aneurysmal dilatation of congenital kinking of the aorta.

PMID- 11581628
TI  - Transaortic repair of blunt traumatic cardiac wall and papillary muscle rupture.

PMID- 11581629
TI  - Sutureless double-patch-and-glue technique for repair of subacute left
      ventricular wall rupture after myocardial infarction.

PMID- 11581630
TI  - Scintigraphic distribution of lymphatic flow in the mediastinum after oral
      administration of radiolabeled lipid and its influx into blood circulation.

PMID- 11581631
TI  - Determinants of perioperative morbidity and mortality after completion
      pneumonectomy.

PMID- 11581633
TI  - Anomalous origin of the left circumflex coronary artery associated with bicuspid
      aortic valve.

PMID- 11581635
TI  - Homegrown common sense.

PMID- 11581636
TI  - Business as usual.

PMID- 11581637
TI  - Declaration of financial interests.

PMID- 11581638
TI  - US stem cell policy comes under fire.

PMID- 11581639
TI  - More biotechs gamble on convertibles.

PMID- 11581640
TI  - Indian seed bill forges new ground.

PMID- 11581641
TI  - US, EU prepare for further biotech food dispute.

PMID- 11581642
TI  - Bayer lapse exposes pharma's vulnerability.

PMID- 11581643
TI  - Analysts: Isis-Lilly deal validates antisense.

PMID- 11581645
TI  - Wine into vinegar--the fall of Cuba's biotechnology.

PMID- 11581647
TI  - US policy on stem cells.

PMID- 11581648
TI  - Back to school.

PMID- 11581651
TI  - The bittersweet promise of glycobiology.

PMID- 11581652
TI  - Knockout drug screens.

PMID- 11581653
TI  - CREating breakthroughs.

PMID- 11581654
TI  - Breaking the code of resistance.

PMID- 11581655
TI  - Hotwiring biosensors.

PMID- 11581657
TI  - Epigenetic regulation of gene structure and function with a cell-permeable Cre
      recombinase.
AB  - Studies of mammalian gene function are hampered by temporal limitations in which
      phenotypes occurring at one stage of development interfere with analysis at later
      stages. Moreover, phenotypes resulting from altered gene activity include both
      direct and indirect effects that may be difficult to distinguish. In the present
      study, recombinant fusion proteins bearing the 12 amino acid membrane
      translocation sequence (MTS) from the Kaposi fibroblast growth factor (FGF-4)
      were used to transduce enzymatically active Cre proteins directly into mammalian
      cells. High levels of recombination were observed in a variety of cultured cell
      types and in all tissues examined in mice following intraperitoneal
      administration. This represents the first use of protein transduction to induce
      the enzymatic conversion of a substrate in living cells and animals and provides
      a rapid and efficient means to manipulate mammalian gene structure and function.

PMID- 11581658
TI  - Transplantation of brain cells assembled around a programmable synthetic
      microenvironment.
AB  - Cell therapy is a promising method for treatment of hematopoietic disorders,
      neurodegenerative diseases, diabetes, and tissue loss due to trauma. Some of the
      major barriers to cell therapy have been partially addressed, including
      identification of cell populations, in vitro cell proliferation, and strategies
      for immunosuppression. An unsolved problem is recapitulation of the unique
      combinations of matrix, growth factor, and cell adhesion cues that distinguish
      each stem cell microenvironment, and that are critically important for control of
      progenitor cell differentiation and histogenesis. Here we describe an approach in
      which cells, synthetic matrix elements, and controlled-release technology are
      assembled and programmed, before transplantation, to mimic the chemical and
      physical microenvironment of developing tissue. We demonstrate this approach in
      animals using a transplantation system that allows control of fetal brain cell
      survival and differentiation by pre-assembly of neo-tissues containing cells and
      nerve growth factor (NGF)-releasing synthetic particles.

PMID- 11581659
TI  - Use of isogenic human cancer cells for high-throughput screening and drug
      discovery.
AB  - Cell-based screening for novel tumor-specific drugs has been compromised by the
      lack of appropriate control cells. We describe a strategy for drug screening
      based on isogenic human cancer cell lines in which key tumorigenic genes have
      been deleted by targeted homologous recombination. As a test case, a yellow
      fluorescent protein (YFP) expression vector was introduced into the colon cancer
      cell line DLD-1, and a blue fluorescent protein (BFP) expression vector was
      introduced into an isogenic derivative in which the mutant K-Ras allele had been
      deleted. Co-culture of both cell lines allowed facile screening for compounds
      with selective toxicity toward the mutant Ras genotype. Among 30,000 compounds
      screened, a novel cytidine nucleoside analog was identified that displayed
      selective activity in vitro and inhibited tumor xenografts containing mutant Ras.
      The present data demonstrate a broadly applicable approach for mining therapeutic
      agents targeted to the specific genetic alterations responsible for cancer
      development.

PMID- 11581660
TI  - Quantitative profiling of differentiation-induced microsomal proteins using
      isotope-coded affinity tags and mass spectrometry.
AB  - An approach to the systematic identification and quantification of the proteins
      contained in the microsomal fraction of cells is described. It consists of three
      steps: (1) preparation of microsomal fractions from cells or tissues representing
      different states; (2) covalent tagging of the proteins with isotope-coded
      affinity tag (ICAT) reagents followed by proteolysis of the combined labeled
      protein samples; and (3) isolation, identification, and quantification of the
      tagged peptides by multidimensional chromatography, automated tandem mass
      spectrometry, and computational analysis of the obtained data. The method was
      used to identify and determine the ratios of abundance of each of 491 proteins
      contained in the microsomal fractions of naive and in vitro- differentiated human
      myeloid leukemia (HL-60) cells. The method and the new software tools to support
      it are well suited to the large-scale, quantitative analysis of membrane proteins
      and other classes of proteins that have been refractory to standard proteomics
      technology.

PMID- 11581661
TI  - Informatics and multiplexing of intact protein identification in bacteria and the
      archaea.
AB  - Although direct fragmentation of protein ions in a mass spectrometer is far more
      efficient than exhaustive mapping of 1-3 kDa peptides for complete
      characterization of primary structures predicted from sequenced genomes, the
      development of this approach is still in its infancy. Here we describe a
      statistical model (good to within approximately 5%) that shows that the database
      search specificity of this method requires only three of four fragment ions to
      match (at +/-0.1 Da) for a 99.8% probability of being correct in a database of
      5,000 protein forms. Software developed for automated processing of protein ion
      fragmentation data and for probability-based retrieval of whole proteins is
      illustrated by identification of 18 archaeal and bacterial proteins with
      simultaneous mass-spectrometric (MS) mapping of their entire primary structures.
      Dissociation of two or three proteins at once for such identifications in
      parallel is also demonstrated, along with retention and exact localization of a
      phosphorylated serine residue through the fragmentation process. These conceptual
      and technical advances should assist future processing of whole proteins in a
      higher throughput format for more robust detection of co- and post-translational
      modifications.

PMID- 11581662
TI  - Designing a polyvalent inhibitor of anthrax toxin.
AB  - Screening peptide libraries is a proven strategy for identifying inhibitors of
      protein-ligand interactions. Compounds identified in these screens often bind to
      their targets with low affinities. When the target protein is present at a high
      density on the surface of cells or other biological surfaces, it is sometimes
      possible to increase the biological activity of a weakly binding ligand by
      presenting multiple copies of it on the same molecule. We isolated a peptide from
      a phage display library that binds weakly to the heptameric cell-binding subunit
      of anthrax toxin and prevents the interaction between cell-binding and enzymatic
      moieties. A molecule consisting of multiple copies of this nonnatural peptide,
      covalently linked to a flexible backbone, prevented assembly of the toxin complex
      in vitro and blocked toxin action in an animal model. This result demonstrates
      that protein-protein interactions can be inhibited by a synthetic, polymeric,
      polyvalent inhibitor in vivo.

PMID- 11581663
TI  - Genetic rescue of an endangered mammal by cross-species nuclear transfer using
      post-mortem somatic cells.
AB  - Since the advent of procedures for cloning animals, conservation biologists have
      proposed using this technology to preserve endangered mammals. Here we report the
      successful cloning of a wild endangered animal, Ovis orientalis musimon, using
      oocytes collected from a closely related, domesticated species, Ovis aries. We
      injected enucleated sheep oocytes with granulosa cells collected from two female
      mouflons found dead in the pasture. Blastocyst-stage cloned embryos transferred
      into sheep foster mothers established two pregnancies, one of which produced an
      apparently normal mouflon. Our findings support the use of cloning for the
      expansion of critically endangered populations.

PMID- 11581664
TI  - Overexpression of a cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase
      in tobacco enhances photosynthesis and growth.
AB  - Transgenic tobacco plants expressing a cyanobacterial fructose-1,6/sedoheptulose
      1,7-bisphosphatase targeted to chloroplasts show enhanced photosynthetic
      efficiency and growth characteristics under atmospheric conditions (360 p.p.m.
      CO2). Compared with wild-type tobacco, final dry matter and photosynthetic CO2
      fixation of the transgenic plants were 1.5-fold and 1.24-fold higher,
      respectively. Transgenic tobacco also showed a 1.2-fold increase in initial
      activity of ribulose 1,5 bisphosphate carboxylase/oxygenase (Rubisco) compared
      with wild-type plants. Levels of intermediates in the Calvin cycle and the
      accumulation of carbohydrates were also higher than those in wild-type plants.
      This is the first report in which expression of a single plastid-targeted enzyme
      has been shown to improve carbon fixation and growth in transgenic plants.

PMID- 11581665
TI  - Feeder-free growth of undifferentiated human embryonic stem cells.
AB  - Previous studies have shown that maintenance of undifferentiated human embryonic
      stem (hES) cells requires culture on mouse embryonic fibroblast (MEF) feeders.
      Here we demonstrate a successful feeder-free hES culture system in which
      undifferentiated cells can be maintained for at least 130 population doublings.
      In this system, hES cells are cultured on Matrigel or laminin in medium
      conditioned by MEF. The hES cells maintained on feeders or off feeders express
      integrin alpha6 and beta1, which may form a laminin-specific receptor. The hES
      cell populations in feeder-free conditions maintained a normal karyotype, stable
      proliferation rate, and high telomerase activity. Similar to cells cultured on
      feeders, hES cells maintained under feeder-free conditions expressed OCT-4,
      hTERT, alkaline phosphatase, and surface markers including SSEA-4, Tra 1-60, and
      Tra 1-81. In addition, hES cells maintained without direct feeder contact formed
      teratomas in SCID/beige mice and differentiated in vitro into cells from all
      three germ layers. Thus, the cells retain fundamental characteristics of hES
      cells in this culture system and are suitable for scaleup production.

PMID- 11581666
TI  - A method for the amidation of recombinant peptides expressed as intein fusion
      proteins in Escherichia coli.
AB  - The increasing use of peptides as pharmaceutical agents, especially in the
      antiviral and anti-infective therapeutic areas, requires cost-effective
      production on a large scale. Many peptides need carboxy amidation for full
      activity or prolonged bioavailability. However, this modification is not possible
      in prokaryotes and must be done using recombinant enzymes or by expression in
      transgenic milk. Methods employing recombinant enzymes are appropriate for small
      scale production, whereas transgenic milk expression is suitable for making
      complex disulfide-containing peptides required in large quantity. Here we
      describe a method for making amidated peptides using a modified self-cleaving
      vacuolar membrane ATPase (VMA) intein expression system. This system is suitable
      for making amidated peptides at a laboratory scale using readily available
      constructs and reagents. Further improvements are possible, such as reducing the
      size of the intein to improve the peptide yields (the VMA intein comprises 454
      amino acids) and, if necessary, secreting the fusion protein to ensure correct N
      terminal processing to the peptide. With such developments, this method could
      form the basis of a large-scale cost-effective system for the bulk production of
      amidated peptides without the use of recombinant enzymes or the need to cleave
      fusion proteins.

PMID- 11581668
TI  - Designing an optimal intellectual property system for plants: a US Supreme Court
      debate.

PMID- 11581672
TI  - Bioethics programs evolve as they grow.

PMID- 11582511
TI  - Measles virus interactions with cellular receptors: consequences for viral
      pathogenesis.
AB  - Although CNS complications occurring early and late after acute measles are a
      serious problem and often fatal, the transient immunosuppression lasting for
      several weeks after the rash is the major cause of measles-related morbidity and
      mortality worldwide. This review is focused on the interactions of measles virus
      (MV) with cellular receptors on neural and lymphoid cells which are important
      elements in viral pathogenesis. First, the cognate MV receptors, CD46 and CD150,
      are important components of viral tropism by mediating binding and entry. Second,
      however, additional unknown cellular surface molecules may (independently of
      viral uptake) after interaction with the MV glycoprotein complex act as signaling
      molecules and thereby modulate cellular survival, proliferation, and specific
      functions.

PMID- 11582512
TI  - Infections of the central nervous system of suspected viral origin: a
      collaborative study from Finland.
AB  - We studied 3231 patients with acute central nervous system (CNS) symptoms of
      suspected viral origin to elucidate the current etiologic spectrum. In 46% of the
      cases, a viral finding was observed. Varicella-zoster virus (VZV) was the main
      agent associated with encephalitis, as well as meningitis and myelitis. VZV
      comprised 29% of all confirmed or probable etiologic agents. Herpes simplex virus
      (HSV) and enteroviruses accounted 11% each, and influenza A virus 7%. VZV seems
      to have achieved a major role in viral infections of CNS. In encephalitis in our
      population, VZV is clearly more commonly associated with these neurological
      diseases than HSV. The increase in VZV findings may in part be a pseudophenomenon
      due to improved diagnostic methods, however, a true increase may have occurred
      and the pathogenetic mechanisms behind this should be elucidated.

PMID- 11582513
TI  - CD8-deficient SJL mice display enhanced susceptibility to Theiler's virus
      infection and increased demyelinating pathology.
AB  - Theiler's murine encephalomyelitis virus (TMEV) infection of the central nervous
      system (CNS) induces a chronic, progressive demyelinating disease in susceptible
      mouse strains characterized by inflammatory mononuclear infiltrates and spastic
      hind limb paralysis. Our lab has previously demonstrated a critical role for TMEV
      and myelin-specific CD4(+) T cells in initiating and perpetuating this
      pathology. It has however, also been shown that the MHC class I loci are
      associated with susceptibility/resistance to TMEV infection and persistence. For
      this reason, we investigated the contribution of CD8(+) T cells to the TMEV
      induced demyelinating pathology in the highly susceptible SJL/J mouse strain.
      Here we show that beta2M-deficient SJL mice have similar disease incidence rates
      to wild-type controls, however beta2M-deficient mice demonstrated earlier onset
      of clinical disease, elevated in vitro responses to TMEV and myelin proteolipid
      (PLP) epitopes, and significantly higher levels of CNS demyelination and
      macrophage infiltration at 50 days post-infection. beta2M-deficient mice also
      displayed a significant elevation in persisting viral titers, as well as an
      increase in macrophage-derived pro-inflammatory cytokine mRNA expression in the
      spinal cord at this same time point. Taken together, these results indicate that
      CD8(+) T cells are not required for clinical or histologic disease initiation or
      progression in TMEV-infected SJL mice. Rather, these data stress the critical
      role of CD4(+) T cells in this capacity and further emphasize the potential for
      CD8(+) T cells to contribute to protection from TMEV-induced demyelination.

PMID- 11582514
TI  - Multiple regions of the murine coronavirus spike glycoprotein influence
      neurovirulence.
AB  - The spike (S) glycoprotein of mouse hepatitis virus (MHV) is a major determinant
      of neurovirulence. Using targeted recombination we previously demonstrated that
      the S gene of the highly neurovirulent MHV-4 conferred a dramatic increase in
      neurovirulence to the mildly neurovirulent MHV-A59. To identify the genetic
      determinants of neurovirulence within the MHV-4 spike, we generated isogenic
      recombinant viruses containing various MHV-4/MHV-A59 chimeric spike genes, and
      studied their phenotypes in vivo. The MHV-4/MHV-A59 chimeric spike genes
      consisted of either reciprocal exchanges between the S1 and S2 spike subunits, or
      smaller exchanges specifically in the hypervariable region (HVR) of S1. The
      chimeric spike gene containing recombinants all exhibited efficient replication
      in vitro, yet many were severely attenuated for virulence in vivo. Furthermore,
      these attenuated recombinants exhibited decreased titers of infectious virus in
      the brain relative to the parental recombinant viruses containing the full-length
      MHV-4 or MHV-A59 spike genes. This is the first report that compares the
      neurovirulence and pathogenesis of isogenic viruses with defined alterations in
      the MHV spike protein. From these studies, it appears that the interactions of
      multiple regions of the MHV spike, including the HVR, act in concert to allow for
      efficient infection of and virulence in the murine central nervous system.

PMID- 11582515
TI  - Sequence analysis of the S gene of recombinant MHV-2/A59 coronaviruses reveals
      three candidate mutations associated with demyelination and hepatitis.
AB  - Coronaviruses, mouse hepatitis virus (MHV) strains, exhibit various degrees of
      neurotropism and hepatotropism following intracerebral (IC) infection of 4-week
      old C57Bl/6 mice. Whereas MHV-A59 produces acute meningitis, encephalitis,
      hepatitis, and chronic demyelination, a closely related strain, MHV-2, produces
      only acute meningitis and hepatitis. We previously reported that the spike
      glycoprotein gene of MHV contains determinants of demyelination and hepatitis. To
      further investigate the site of demyelination and hepatitis determinants within
      the S gene, we sequenced the S gene of several nondemyelinating recombinant
      viruses. We found that three encephalitis-positive, demyelination-negative,
      hepatitis-negative recombinant viruses have an MHV-A59-derived S gene, which
      contains three identical point mutations (I375M, L652I, and T1087N). One or more
      of the sites of these mutations in the MHV-A59 genome are likely to contribute to
      demyelination and hepatitis.

PMID- 11582516
TI  - Adeno-associated virus-mediated delivery of glial cell line-derived neurotrophic
      factor protects motor neuron-like cells from apoptosis.
AB  - Motor neuron disorders including amyotrophic lateral sclerosis may benefit from
      the induction of neurotrophic factors such as glial cell line-derived
      neurotrophic factor (GDNF) that are known to be trophic and protective for motor
      neurons. However, the application of such factors is limited by an inability to
      successfully target their expression in the nervous system. In this study we
      investigate the potential of using adeno-associated virus (AAV) as a vector for
      gene delivery into motor neuron-like cells. In initial experiments on the motor
      neuron cell line NSC-19 using a recombinant AAV vector expressing the reporter
      gene beta-galactosidase (AAV-LacZ), we successfully demonstrate the utility of
      AAV for gene transfer. In addition, a recombinant AAV vector expressing GDNF was
      shown to express and secrete high levels of the neurotrophic factor into the
      surrounding media of NSC-19 infected cells. Finally, the AAV-GDNF vector is
      demonstrated to act in a neuroprotective fashion. Withdrawal of trophic support
      from NSC-19 cells through serum deprivation results in a subsequent increase in
      the number of cells entering apoptosis. However, the percentage of apoptotic
      cells are significantly reduced in cells infected with the AAV-GDNF vector, as
      compared to AAV-LacZ or uninfected controls. This work demonstrates the potential
      of using AAV as a vector in motor neuron-like cells and should prove important in
      devising future gene therapy strategies for the treatment of in vivo motor neuron
      disorders.

PMID- 11582517
TI  - Autonomic nervous system innervation of lymphoid territories in spleen: a
      possible involvement of noradrenergic neurons for prion neuroinvasion in natural
      scrapie.
AB  - In experimental as well as in natural scrapie, transmissible spongiform
      encephalopathies (TSEs), the infectious agent, closely related to PrPsc, an
      abnormal isoform of the cellular prion protein, invades and replicates in
      lymphoid organs such as spleen before affecting the brain. To clarify the
      cellular requirements for the possible neuroinvasion of scrapie agent from the
      spleen to the central nervous system, we have studied the sympathetic innervation
      within the lymphoid territories of the spleen. These noradrenergic fibers
      originating from the coeliomesenteric ganglia were examined with regard to PrPsc
      associated cells in spleen of adult sheep severely affected with natural scrapie.
      Using a double immunolabelling strategy, we demonstrated the proximity of
      noradrenergic endings with PrPsc-accumulating cells, strengthening its possible
      implication in the neuroinvasion process.

PMID- 11582518
TI  - Protective effect of glutathione in HIV-1 lytic peptide 1-induced cell death in
      human neuronal cells.
AB  - To elucidate the pathogenic mechanisms involved in neurodegeneration in AIDS
      patients with cognitive deficits, we have examined the toxic effect of the
      lentivirus lytic peptide 1 (LLP-1) corresponding to the carboxyl terminus of HIV
      1 transmembrane glycoprotein gp41 on human neuronal and glial cell lines. LLP-1
      induced a significant lactate dehydrogenase (LDH, a marker of cell death) release
      from these cells in a concentration- and time-dependent manner, while the
      noncytolytic LLP-1 analog 2 had little effect. Application of LLP-1 to SH-SY5Y, a
      well-characterized human neuronal cell line, caused the decline of intracellular
      glutathione (GSH) content that appeared to occur before a significant LDH
      release. Furthermore, LLP-1 elicited a significant loss of mitochondrial function
      as measured by mitochondrial transmembrane potential (MTP). Among the reducing
      agents and antioxidants tested, GSH and a GSH prodrug N-acetylcysteine (NAC)
      provided protection against LLP-1-induced neuronal cell death, evidently by
      restoring the intracellular GSH levels and blocking the disruption of
      mitochondrial integrity. Thus, gp41-derived LLP-1 may be a potential neurotoxic
      agent capable of causing the intracellular GSH depletion and disturbing the
      mitochondrial function, possibly contributing to the neurodegenerative cascade as
      seen in HIV-1-associated dementia. Our data indicate that restoring both GSH
      concentration and mitochondrial function may hold promise as possible therapeutic
      strategies for slowing disease progression of dementia in AIDS patients.

PMID- 11582520
TI  - HveC (nectin-1) is expressed at high levels in sensory neurons, but not in motor
      neurons, of the rat peripheral nervous system.
AB  - The entry of herpes simplex virus (HSV)-1 into cells is a complex process
      mediated in part by the binding of the HSV glycoprotein D (gD) to a specific
      cellular receptor identified as HveC, or nectin-1. We examined the distribution
      of HveC in sensory and motor neurons of the peripheral nervous system (PNS) by
      immunocytochemistry. HveC is expressed at high levels in sensory neurons of
      dorsal root ganglion and their peripheral axons, at lower levels in motor neurons
      of spinal cord, and without detectable expression in motor nerve terminals at the
      neuromuscular junction. These results have implications regarding the tropism of
      HSV to specific neuronal populations, and for the construction of HSV-based
      vectors for the peripheral nervous system.

PMID- 11582519
TI  - Enhanced proteolysis of IkappaBalpha and IkappaBbeta proteins in astrocytes by
      Moloney murine leukemia virus (MoMuLV)-ts1 infection: a potential mechanism of NF
      kappaB activation.
AB  - Moloney murine leukemia virus (MoMuLV)-ts1-mediated neuronal degeneration in mice
      is likely due to loss of glial support and release of inflammatory cytokines and
      neurotoxins from surrounding ts1-infected glial cells including astrocytes. NF
      kappaB is a transcription factor that participates in the transcriptional
      activation of a variety of immune and inflammatory genes. We investigated whether
      ts1 activates NF-kappaB in astrocytes and examined the mechanism(s) responsible
      for the activation of NF-kappaB by ts1 infection in vitro. Here we present
      evidence that ts1 infection of astrocytes in vitro activates NF-kappaB by
      enhanced proteolysis of the NF-kappaB inhibitors, IkappaBalpha and IkappaBbeta.
      In in vitro studies using protease inhibitors, IkappaBalpha proteolysis in ts1
      infected astrocytes was significantly blocked by a specific calpain inhibitor
      calpeptin but not by MG-132, a specific proteasome inhibitor, whereas rapid
      IkappaBbeta proteolysis was blocked by MG-132. Furthermore, treatment with MG-132
      increased levels of multiubiquitinated IkappaBbeta protein in ts1-infected
      astrocytes. These results indicate that the calpain proteolysis is a major
      mechanism of IkappaBalpha proteolysis in ts1-infected astrocytes. Additionally,
      ts1 infection of astrocytes in vitro increased expression of inducible nitric
      oxide synthase (iNOS), a NF-kappaB-dependent gene product. Our results suggest
      that NF-kappaB activation in ts1-infected astrocytes is mediated by enhanced
      proteolysis of IkappaBalpha and IkappaBbeta through two different proteolytic
      pathways, the calpain and ubiquitin-proteasome pathways, resulting in increased
      expression of iNOS, a NF-kappaB-dependent gene.

PMID- 11582521
TI  - Diazepam inhibits HIV-1 Tat-induced migration of human microglia.
AB  - During HIV-1 encephalitis, the chemotaxis-inducing activity of Tat may enhance
      the viral life cycle through recruitment of additional susceptible microglial
      cells to foci of infection. Benzodiazepines (BDZs) readily penetrate the blood
      brain barrier and are known to possess anti-inflammatory properties. Pretreatment
      of human microglial cells with peripheral (Ro5-4864) and mixed (diazepam), but
      not central (clonazepam), benzodiazepine receptor ligands was found to potently
      suppress HIV-1 Tat-induced chemotaxis. Application of Tat to microglial cells
      evokes an increase in intracellular calcium concentration ([Ca(2+)]i) that
      rapidly desensitizes the cells. Diazepam's inhibitory effect was associated with
      its ability to block Tat-induced [Ca(2+)]i mobilization. These data support the
      notion that through their effects on microglia, peripheral BDZ receptor ligands
      could alter the neuropathogenesis of HIV-1.

PMID- 11582524
TI  - [Leprosy - An overview from a pediatric perspective].
AB  - Worldwide tourism is an increasing industry. One result of this phenomenon is the
      occurrence of imported infectious diseases, as recently observed even in Germany.
      Leprosy ranks high among dreaded infectious diseases from tropical and
      subtropical countries. It remains a major health threat despite marked
      improvements in diagnosis and therapy. This was achieved by a better
      understanding of bacteriological and immunological mechanisms over the past
      decades, resulting in a decline of Leprosy's incidence.

PMID- 11582522
TI  - CXCR4 is the primary receptor for feline immunodeficiency virus in astrocytes.
AB  - Feline astrocytes were productively infected with the Crandell feline kidney
      (CrFK) cell-adapted feline immunodeficiency virus (FIV) Petaluma strain in a
      primary culture. They expressed mRNA of CXCR4, and the FIV infection was blocked
      by stromal cell-derived factor 1alpha (SDF-1alpha), SDF-1beta, or the bicyclam
      AMD3100 in a dose-dependent manner. These observations suggest that, like FIV
      infection in CrFK cells and lymphocytes, the virus uses CXCR4 as a primary
      receptor for infecting astrocytes and this can be a possible natural model for
      AIDS dementia complex.

PMID- 11582523
TI  - [Variants of inborn errors of metabolism with late onset but nevertheless life
      threatening course].
AB  - BACKGROUND: There is a growing number of inborn errors of metabolism (IEM) with
      late onset but nevertheless life threatening course. PATIENTS: Patients with late
      onset variants of urea cycle defects, fatty acid oxidation defects and organic
      acidurias are demonstrated. METHODS: Biochemical, enzymatic, molecular methods
      and especially tandem mass spectrometry (TMS) are used for diagnostic purposes.
      RESULTS: IEM variants with late onset are difficult to be detected. TMS has some
      advantages as the simple sampling of dried blood on filter paper cards and the
      simultaneous detection of a broad spectrum of disturbances in amino acids and
      acylcarnitines. This may facilitate a prompt diagnosis. Asymptomatic persons not
      only carry an unrecognized risk for severe metabolic decompensation but also pass
      on their mutation of IEM and the associated disease risk to the next generation
      (Non-disease). CONCLUSION: TMS, which is used in newborn screening centers is
      very convenient to establish a prompt diagnosis in some unexpected late onset
      metabolic crisis following surgeries, infections or other catabolic stress.
      Furthermore TMS may be a suitable and rapid adjunct method to improve
      transplantation management.

PMID- 11582525
TI  - [Chronic recurrent multifocal osteomyelitis-- I. Review].
AB  - Juvenile and adolescent "Chronic Recurrent Multifocal Osteomyelitis" (CRMO) is
      described on the basis of literature and analysis of 43 own cases (23 cases in
      children or adolescents). This systemic, non-purulent inflammatory disease occurs
      mainly metaphyseal in long bones, in pelvic bones or as spondylitis and is not as
      rare as it seemed. Basis of the disease is a primarily chronic, sterile, in phase
      of onset often monotopic (e.g. clavicle) and later frequently polytopic
      osteomyelitis, possibly triggered by an immuno-pathological process (e.g.
      Proprionibacterium acnes), and showing histologically plasmacellular invasion and
      a sclerosing process in different stages. Association with pustulous dermatosis
      (psoriasis, acne, palmo-plantar pustulosis) is found in about 25 % of children
      and adolescents and in more than 50 % of the adult patients. 5 differents types
      of distribution of osteomyelitic lesions can be found by using Te99m-bone scan
      primarily, of which the "pelvic type" is the most common. Because of the close
      neighbourhood of meta-/epiphyseal osteomyelitic focuses, "sympathetic arthritis"
      with synovitis is seen frequently. A therapeutic approach with azithromycine and
      calcitonine is presented.

PMID- 11582526
TI  - [Pelvic type of chronic recurrent multifocal osteomyelitis].
AB  - We report about the juvenile and adolescent pelvic type of CRMO in 7 girls and 4
      boys. The results show from solitary up to 7 pelvic lesions (average 3 lesions)
      predominantly in the acetabular and paraacetabular region (sometimes with hip
      joint effusion as a sign for concomitant coxitis).Tc99m-bone-scan is helpful to
      evaluate exactly the pattern of bone affection. We find 3 stages of an primarily
      chronic, non-purulent osteomyelitis going along with a "plasma-cell-sclerotic
      process", leading to a Garre-type sclerosing end-stage, which probably heals
      after some years spontaneously, projecting on clinical symptoms and radiological
      appearance. The concomitant coxitis ("sympathetic coxitis") is clinically often
      in the foreground, but reversible. Pain in case of CRMO responds surprisingly
      well on medication with acithromycine. Knowing about CRMO in its different
      clinical appearances - especially concerning what we call "sympathetic coxitis" -
      can be a useful for pediatric rheumatologists and orthopedic surgeons, as well as
      MRI-focused radiologists and pathologists. Therapy might find a useful drug in
      acithromycine. In conclusion we d like to point out, that CRMO is one entity
      under the "roof" of the so called SAPHO-syndrome, which again shows us, that
      SAPHO-syndrome ist not a diagnosis itself but more a sign-post on the way to a
      correct diagnosis.

PMID- 11582527
TI  - Successful treatment of Pseudomonas aeruginosa respiratory tract infection with a
      sugar solution--a case report on a lectin based therapeutic principle.
AB  - BACKGROUND: Airway infections with Pseudomonas aeruginosa often represent a life
      threatening event in immuno-compromised patients or patients with Cystic
      Fibrosis. The adhesion of this bacterium to surfaces such as the airway
      epithelium is mediated by two lectins, sugar binding proteins. In addition to
      their adhesive properties, these lectins have been shown to stop human ciliary
      beating thus compromising the mucociliary clearance as an important non-specific
      defence mechanism of the airways. Inhibition of these lectins by their specific
      sugars galactose and fucose, respectively, could therefore be of benefit in the
      elimination therapy of P. aeruginosa. CASE REPORT: An infant suffering from P.
      aeruginosa airway infection after chemotherapy for neuroblastoma, which could not
      successfully be treated by antibiotics, was subjected to a series of additional
      galactose/fucose inhalations, which eliminated the germ as evidenced by
      microbiological testing. This is the first report suggesting the effectiveness of
      a lectin-based therapeutic principle in P. aeruginosa airway infection.
      CONCLUSION: The competitive inhibition of P. aeruginosa lectins by the lectin
      specific sugars galactose and fucose may overcome particular mechanisms of
      bacterial resistance in patients with P. aeruginosa airway infection. This
      underlying biochemical mechanism and the outcome of our patient suggest a
      clinical benefit of this novel therapeutic approach for immunocompromised
      patients or patients with cystic fibrosis suffering from infection with P.
      aeruginosa.

PMID- 11582528
TI  - [Pseudo-Acanthosis nigricans in a 12 year old boy after kidney transplantation].
AB  - Cutaneous lesions under immunosuppressive therapy require a specific diagnostic
      approach. We present the case of a 12 year old boy who developed pseudo
      acanthosis nigricans 3 months after renal transplantation.

PMID- 11582529
TI  - [Blood pressure difference between upper arm and thigh, and aortic stiffness in
      healthy subjects and in patients after coarcectomy].
AB  - BACKGROUND: The blood pressure difference between the right arm and the legs is
      often used as an estimate of a possible gradient across a coarctation or
      recoarctation aortae. We wanted to test the reliability of this hypotheses while
      estimating the local stiffness of the aortae ascendens and abdominalis. PATIENTS:
      We examined 50 healthy children and adolescents as well as 50 patients of a
      similar age after repair of an coarctation aortae. There was no relevant
      recoarctation on echocardiography or magnet resonance tomography. METHODS: We
      measured in all patients the blood pressure by oscillometry three times on the
      right upper arm and thigh. At the same time we measured the systolic and
      diastolic diameter of the aorta before the branching of the truncus
      brachiocephalicus and the branching of the truncus coeliacus. The local stiffness
      was calculated, using the stiffness index b, from the aortic diameter and the
      corresponding blood pressure. RESULTS: The systolic blood pressure difference
      showed in healthy subjects and patients after coarctation a wide range (about 60
      mm Hg). The diastolic and mean blood pressure showed a slightly smaller range.
      There was no significant difference in this respect between the two groups. The
      stiffness index beta was elevated after coarcectomy in the aorta ascendens
      compared to healthy subjects. The local stiffness of the abdominal aortae were
      similar in both groups and showed a similar increase with advancing age.
      DISCUSSION: The blood pressure difference between the upper arm and thigh showed
      a wide range. Therefore is the blood pressure difference an unreliable tool to
      estimate the severity of a re-coarctation. The local stiffness of the aorta
      ascendens was elevated after coarctation and implied at least a partial loss of
      the Windkessel. The local stiffness in the aorta abdominalis was normal after
      coarctation repair.

PMID- 11582530
TI  - [Thyroglossal duct cysts in paediatric patients: early operative intervention
      reduces rate of complications].
AB  - BACKGROUND: Thyroglossal duct cysts arise from mucus production in an incomplete
      regressed thyroglossal duct. Often they are only noticed in case of infection or
      secondary fistulation. The operative management is a Sistrunk procedure. METHOD
      AND PATIENTS: In a retrospective study we analyse 26 patients aged 0,3 - 10 years
      with histological confirmed thyroglossal duct cysts, 13 of these (50 %) had signs
      of infection. In 15 patients the cyst was primarily cored out, in 11 patients the
      core out followed a primarily incision and drainage. RESULTS: 5 patients (19 %)
      developed recurrent cysts. Patients with signs of infection or incomplete
      resection of hyoid bone had a high risk of developing recurrence. CONCLUSIONS: We
      propose an early operative treatment for thyroglossal duct cysts with a complete
      Sistrunk procedure.

PMID- 11582531
TI  - [Dentogenic infection due to Streptococcus constellatus in a child].
AB  - An 8-year-old boy was admitted with a pain-full swelling at the right mandible
      and symptoms of septicemia. The illness was caused by a dental infection due to
      Streptococcus constellatus proved by isolation from blood culture, the origin was
      a decayed tooth. Treatment comprised suitable antibiotics, extraction of the
      tooth and local irrigations with chlorhexidine solution. General condition
      improved rapidly, the local situation rather slowly, however.

PMID- 11582532
TI  - [Femur-fibula-ulna (FFU) complex in the 33rd week of gestation: ultrasonography,
      radiology, pathology and differential diagnosis. Case report].
AB  - We present a case of a 27 year old I. gravida, I. para. Despite of regular
      ultrasonographic examination the diagnosis of skeletal malformation at the fetus
      was not before 33. weeks of gestation. It was the rare type of a bothside femur
      fibula-ulna (FFU) complex. The FFU-complex is a no lethal malformation with
      typical unilateral combination from defects of femur and fibula, with
      contralateral defect of ulna. Dependent to involvement of malformated limbs the
      FFU-complex is classifiable in four groups. Only in 10 % all limbs are affected.
      Our case (type IV) showed a peromelia of both upper limbs with stumps of humeri,
      bothside aplasia of fibula and missing from 4. and 5. toes. There fetus were
      without nonlimb congenital abnormalities. The etiology of FFU-complex is unknown,
      the occurrence sporadic. There are never found genetic abnormalities. Familial
      recurrence is not described. There is no maternal or paternal age effect on FFU
      complex. The differential diagnosis must include malformations with reduction
      anomalies of extremities, like thalidomide syndrome, splenogonadal fusion with
      limb malformations, Roberts syndrome, oroacral complex or acheiropodia. Mark off
      are amniotic band too.

PMID- 11582533
TI  - Vasorelaxing and antioxidant constituents from Hernandia nymphaeifolia.
AB  - Three new alkaloids, (+)-nymphaedaline (1), oxo-O-methylbulbocapnine (2), and (+)
      laetine (3), have been isolated from the trunk bark of Hernandia nymphaeifolia.
      The structures of these new compounds were elucidated by spectroscopic analysis.
      Among the isolates of this plant obtained till now, sixteen compounds show
      effective inhibitory activities on the contraction of vascular smooth muscles
      induced by high K+ (80 mM) or norepinephrine (3 microM). In addition, eight
      compounds showed effective antioxidant activities in scavenging the stable free
      radical, diphenyl-picryl-hydrazyl (DPPH).

PMID- 11582534
TI  - Inhibition of trypsin and chymotrypsin by anti-inflammatory triterpenoids from
      Compositae flowers.
AB  - Taraxastane, oleanane, ursane, lupane, taraxane, cycloartane, dammarane and
      tirucallane triterpenoids isolated from flowers of Compositae plants have been
      previously reported to exhibit anti-inflammatory effects and are variously
      competitive and non-competitive inhibitors of the serine proteases trypsin and
      chymotrypsin. The general features of those triterpenoids found to be protease
      inhibitors are having a hydroxy group and an appropriate side chain in the region
      of the molecule distal to the 3-hydroxy group. However, fatty acid esterification
      of the triterpenoid 3-hydroxy group can have a marked effect on inhibitor
      effectiveness. This suggests a possible means of rapid alteration of the plant
      defensive complement in vivo and of the bioactivity of these anti-inflammatory
      compounds.

PMID- 11582535
TI  - Intracellular calcium mobilization as a target for the spasmolytic action of
      scopoletin.
AB  - The coumarin scopoletin was isolated in a pure form from the roots of Brunfelsia
      hopeana Benth. (Solanaceae). In isolated rat aortic rings, scopoletin (26-520
      microM) inhibited to approximately the same extent the contractions induced by a
      variety of substances, including phenylephrine, potassium chloride, serotonin and
      PGF(2) (alpha). The effect of the coumarin on phenylephrine-induced contractions
      was not affected by endothelium removal or NO-synthase blockade by L-NAME (100
      microM). Scopoletin (78 - 590 microM) antagonized in a concentration-dependent
      manner (IC(50) = 300 +/- 20 microM, n = 5), transient contractions in Ca(2+)-free
      media induced by noradrenaline, but not those induced by caffeine. Also,
      scopoletin did not interfere with the refilling of noradrenaline-sensitive
      intracellular calcium stores. It is suggested that the non-specific spasmolytic
      action of scopoletin can be attributed, at least in part, to its ability to
      inhibit the intracellular calcium mobilization from the noradrenaline-sensitive
      stores.

PMID- 11582536
TI  - Effects of hydrastine derivatives on dopamine biosynthesis in PC12 cells.
AB  - The effects of hydrastine derivatives on dopamine biosynthesis in PC12 cells were
      investigated. Treatments of PC12 cells with (1R,9S)-beta-hydrastine hydrochloride
      [(+)-beta-hydrastine HCl] and (1R,9S)-beta-hydrastine [(-)-beta-hydrastine]
      showed 50.6 % and 33.1 % inhibition of dopamine content at a concentration of 10
      microM for 48 h. However, (1S,9R)-beta-hydrastine [(+)-beta-hydrastine] and
      hydrastinine hydrochloride did not reduce dopamine content. The IC(50) values of
      (1R,9S)-beta-hydrastine hydrochloride and (1R,9S)-beta-hydrastine were 9.3 microM
      and 20.7 microM , respectively. Next, the intracellular mechanisms of (1R,9S)
      beta-hydrastine hydrochloride in PC12 cells were investigated. Dopamine content
      decreased at 6 h and reached a minimal level at 24 h after the exposure of PC12
      cells to 20 microM (1R,9S)-beta-hydrastine hydrochloride. Tyrosine hydroxylase
      (TH) activity was inhibited at 6 h following the treatment with (1R,9S)-beta
      hydrastine hydrochloride, and was maintained at a reduced level for up to 36 h in
      PC12 cells (17 - 27 % inhibition at 20 microM), whereas TH mRNA level was not
      found to alter for 24 h. However, the level of intracellular Ca++ concentration
      decreased by treatment with (1R,9S)-beta-hydrastine hydrochloride at 20 microM by
      18.4 % inhibition relative to the control level in PC12 cells. These results
      suggest that (1R,9S)-beta-hydrastine hydrochloride contributes partially to the
      decrease in dopamine content by the inhibition of TH activity in PC12 cells.

PMID- 11582537
TI  - Cytotoxic and anti-inflammatory activity of labdane and cis-clerodane type
      diterpenes.
AB  - Two labdane type diterpenes, labd-13(E)-ene,-8alpha,15-diol (1) and labd-13(E)
      ene,-8alpha,15-yl acetate (2) were isolated from the hexane extract of Cistus
      creticus subsp. eriocephalus (Viv.) Greuter & Burdet leaves, while (+)-19-acetoxy
      cis-clerodan-3-en-15-oic acid (3) was isolated from the hexane extract of Cistus
      monspeliensis L. leaves. The compounds were examined for their in vitro
      cytostatic and cytotoxic activity against nine human leukemic cell lines, three
      of which exhibited a multidrug resistant phenotype. They were also evaluated for
      their anti-inflammatory activity in vivo on the back of hairless mice. The
      cytostatic and cytotoxic activity of the tested diterpenes followed the order
      1>2>3. Topical application of the diterpenes on barrier disrupted skin did not
      seem to have a significant contribution to the repair rate of the skin barrier.

PMID- 11582538
TI  - Anti-thrombotic effects of higenamine.
AB  - The anti-platelet and anti-thrombotic effects of higenamine, a
      benzyltetrahydroisoquinoline alkaloid of the roots of Aconitum japonicum
      (Ranunculaceae), were investigated. The degree of platelet aggregation was
      measured with platelet rich plasma (PRP). An acute thrombotic condition was
      induced in mice by the injection of the mixture of collagen and epinephrine. The
      thrombus formation was induced inside the arterio-venous shunt tube installed
      between an abdominal aorta and the renal vein of rats. Higenamine showed
      inhibitory activities to both human and rat platelet aggregation induced by ADP,
      collagen and epinephrine. It was more inhibitory to epinephrine induced
      aggregation (IC(50); 19 and 7.2 microM to human and rat platelets respectively)
      than ADP- or collagen-induced aggregation. The anti-thrombotic effects of
      higenamine were also observed in both mouse acute thrombosis model and rat
      arterio-venous shunt (AV-shunt) models. The oral administration of higenamine (50
      or 100 mg/kg) increased the recovery rates from the acute thrombotic challenge in
      mice and lowered the weight of thrombus formed inside the AV-shunt tube in rats.

PMID- 11582539
TI  - In vitro effect of alkaloids on bloodstream forms of Trypanosoma brucei and T.
      congolense.
AB  - The effect of 34 alkaloids of the piperidine, pyridine, tropane, isoquinoline,
      indole, quinolizidine, quinoline, purine, and steroidal types on the growth of
      Trypanosoma brucei, T. congolense, and human HL-60 cells was investigated in
      vitro. Berbamine, berberine, cinchonidine, cinchonine, emetine, ergotamine,
      quinidine, quinine, and sanguinarine showed trypanocidal activities with ED(50)
      (50% effective dose) values below 10 microM. Berberine, emetine, and quinidine
      were the most active compounds found; their ED(50) values and minimum inhibitory
      concentrations were comparable to those of the antitrypanosomal drugs suramin and
      diminazene aceturate. However, most of these compounds were also cytotoxic. In
      the case of emetine, the ratio of cytotoxic/trypanocidal activity was only 3
      while for quinidine it was 300 indicating that this alkaloid could be a candidate
      for further drug development. DNA intercalation in combination with protein
      biosynthesis inhibition, which is the major mode of action of the active
      alkaloids, could be responsible for the observed trypanocidal and cytotoxic
      effects.

PMID- 11582540
TI  - Capsaicin-like anti-obese activities of evodiamine from fruits of Evodia
      rutaecarpa, a vanilloid receptor agonist.
AB  - Evodiamine, a major alkaloidal principle of Evodia fruits (Evodia rutaecarpa,
      Rutaceae), showed vanilloid receptor agonistic activities comparable to
      capsaicin. The Chinese literature refers to Evodia fruits as a "hot nature" herb.
      In spite of the similarities in the actions of evodiamine and capsaicin in vitro,
      evodiamine has no perceptible taste, including a peppery hot taste. Therefore,
      the effectiveness of evodiamine and the extract of Evodia fruits in preventing
      obesity on male C3H mice, or male SD rats were examined. When evodiamine was
      supplemented at 0.03% of the diet and fed to mice for 12 days, the perirenal fat
      weight became significantly lower than in the control group. The epididymal fat
      mass was also decreased in the evodiamine diet group. When evodiamine was
      supplemented at 0.02% in the form of ethanol extract of Evodia fruits to the high
      fat diet and fed to rats for 21 days, the body weight, the perirenal fat weight,
      epididymal fat weight, the levels of serum free fatty acid, total lipids in the
      liver, triglyceride in the liver, and cholesterol level in the liver were
      significantly reduced as compared with the control diet group. Furthermore, both
      lipolytic activity in the perirenal fat tissue and specific GDP binding in brown
      adipose tissue mitochondria, as the biological index of enhanced heat production,
      were significantly increased in the evodiamine fed rats. Fasting mice
      subcutaneously administered 1-3 mg/kg evodiamine showed decreased core body
      temperature by 1-2 degrees C. This hypothermic effect was prevented by the
      pretreatment of intraperitoneally administered 10 mg/kg capsazepine, a vanilloid
      receptor antagonist. On the other hand, food-sated mice subcutaneously
      administered 1-3 mg/kg evodiamine showed unchanged core body temperature and
      increased tail skin temperature by more than 5 degrees C, suggesting the
      increased energy expenditure by enhanced heat dissipation. In conclusion, we have
      demonstrated that a novel non-pungent vanilloid receptor agonist, evodiamine,
      mimics the characteristic anti-obese effects induced by capsaicin. Evodiamine
      would induce heat loss and heat production at the same time and dissipate food
      energy, preventing the accumulation of perivisceral fat and the body weight
      increase.

PMID- 11582541
TI  - Effect of ginseng saponins on beta-amyloid-suppressed acetylcholine release from
      rat hippocampal slices.
AB  - In view of the facts that ginseng has been shown to improve age-related memory
      deficits and beta-amyloid-related peptides have been suggested to play a
      significant role in memory degeneration in the elderly, the present study was
      carried out to examine the effect of various ginsenosides on beta-amyloid
      peptides-modulated acetylcholine (ACh) release, a key neurotransmitter in memory
      processing, from the hippocampal slices. Addition of beta-amyloid fragment(25 -
      35) (0.01 - 1 microM) in the superfusion medium suppressed the K(+)-evoked [(3)H]
      ACh release from the rat hippocampal slices in a concentration-related manner and
      about 40 % reduction in ACh outflow was observed when incubating with the highest
      concentration of an amyloid fragment (1 microM). Inclusion of the ginsenoside
      components Rb(1) (0.1 microM), but not Rg(1), caused a rightward shift of the
      concentration-response curve of beta-amyloid. The reversal of the beta-amyloid
      inhibited ACh release by Rb(1) was not blocked by tetrodotoxin (1 microM)
      indicating that an interaction occurs at the cholinergic synapse. These results
      suggest that Rb(1) may elicit its anti-amnesic effect by minimizing the
      inhibitory effect of beta-amyloid peptides.

PMID- 11582542
TI  - Cardiovascular effects of the essential oil of Mentha x villosa and its main
      constituent, piperitenone oxide, in normotensive anaesthetised rats: role of the
      autonomic nervous system.
AB  - Cardiovascular effects of intravenous (i. v.) treatment with the essential oil of
      Mentha x villosa (EOMV) were investigated in pentobarbitone-anaesthetised rats.
      Additionally this study examines whether the major constituent of EOMV,
      piperitenone oxide (PO), is the active principle mediating EOMV-induced changes
      in mean aortic pressure (MAP) and heart rate (HR) and whether the autonomic
      nervous system is involved in the mediation of these cardiovascular effects. Two
      samples of EOMV have been tested: one contained 62.32% of PO (sample 1) and the
      other contained a higher percent (95.87%) of PO (sample 2). Intravenous
      injections of bolus doses (1 to 20 mg/kg) of both samples of EOMV elicited
      immediate and dose-dependent decreases in MAP and HR. These cardiovascular
      responses were also observed following i. v. injections of PO (1 to 20 mg/kg).
      However, maximal percent decreases in MAP and HR elicited by sample 2 of EOMV
      were significantly greater than those evoked by sample 1 of EOMV, while they were
      of the same order of magnitude as those elicited by PO. Pretreatment of rats with
      either bilateral vagotomy or i. v. methylatropine (1 mg/kg) did not modify
      significantly the hypotensive and bradycardic responses to EOMV. In contrast,
      pretreatment with i. v. hexamethonium (30 mg/kg) partially, but significantly,
      reduced the bradycardic effects of EOMV without affecting hypotension. The
      present study shows for the first time that i. v. treatment with EOMV in
      pentobarbitone-anaesthetised rats induces hypotensive and bradycardic effects,
      which appear mostly attributed to the actions of the major constituent of EOMV,
      PO. These cardiovascular effects appear to be independent since EOMV-induced
      bradycardia appears dependent upon the presence of an intact and functional
      sympathetic nerve drive to the heart, while EOMV-induced hypotension appears
      independent of the presence of an operational sympathetic nervous system. This
      suggests that hypotensive activity of EOMV may result from its vasodilatory
      effects directly upon vascular smooth muscle.

PMID- 11582543
TI  - A bioassay using the human hepatoblastoma cell line HepG2 for detecting
      phototoxicity of furocoumarins.
AB  - We successfully evaluated the human hepatoblastoma cell line HepG2 as a model to
      assess phototoxicity of coumarins. Five natural furocoumarins were tested and
      their phototoxic activities, obtained by measuring cell viability in the presence
      of UV using the MTT test, were as follows: xanthotoxin (8-MOP) >> heraclenol =
      trichoclin = imperatorin >> peucedanin, both in growing and confluent cell
      cultures. This easy-to-perform, miniaturised, quantitative and sensitive method
      could therefore be used as a primary screening test for phototoxicity of a large
      number of compounds and plant extracts.

PMID- 11582544
TI  - New sesquiterpene lactones from Elephantopus mollis and their leishmanicidal
      activities.
AB  - The leishmanicidal compounds isolated from whole plants of Elephantopus mollis
      H.B.K. were identified as follows. Three new sesquiterpenoid lactones, 2,5-epoxy
      2beta-hydroxy-8alpha-(2-methylpropenoyloxy)-4(15),10(14),11(13)-germacratrien
      12,6alpha-olide, (4betaH)-8alpha-(2-methylpropenoyloxy)-2-oxo-1(5),10(14), 11(13)
      guaiatrien-12,6alpha-olide and (4betaH)-5alpha-hydroxy-8alpha-(2
      methylpropenoyloxy)-1(10),11(13)-guaiadiene-12,6alpha-olide, were isolated from
      Peruvian and Brazilian collections together with four known sesquiterpenoids,
      molephantin, elephantopin, isoelephantopin and 2-deethoxy-2beta
      methoxyphantomolin. They exhibited potent in vitro leishmanicidal activities
      against Leishmania major. The alpha-methylene-gamma-butyrolactone moiety was
      found to be essential to the potent leishmanicidal effect observed.

PMID- 11582545
TI  - Topical anti-inflammatory activity of a new germacrane derivative from Achillea
      pannonica.
AB  - The topical anti-inflammatory activity of a germacrane derivative [1,4-dihydroxy
      germacra-5E-10(14)-diene; DHGD] isolated from Achillea pannonica Scheele
      (Asteraceae) was investigated employing the Croton oil-induced dermatitis in the
      mouse ear. Its effects on the oedematous response and on leukocytes infiltration
      are described. The germacrane derivative significantly inhibited ear oedema in a
      dose-dependent manner, with an ID(50) of 0.40 micromol/cm(2). DHGD (0.75
      micromol/cm(2)) provoked a global inhibition of the oedematous response (61 %)
      higher than that induced by an equimolar dose of indomethacin (43 %) within 24
      hours; the reduction induced by hydrocortisone (0.10 micromol/cm(2)) was 68 %.
      The effect of DHGD (61 % inhibition) was higher than that of the equimolar dose
      of indomethacin (51 % inhibition) also on granulocytes recruitment at the site of
      inflammation. Hydrocortisone (0.10 micromol/cm(2)) reduced the cellular
      infiltrate by 44 %.

PMID- 11582546
TI  - Triterpene constituents from the stem bark of Pinus luchuensis and their DNA
      topoisomerase II inhibitory effect.
AB  - Nine lanostane and serratane-type triterpenes including two unknown compounds
      were isolated from the stem bark of Pinus luchuensis. These new compounds were
      characterized as 3-oxolanost-9(11)-ene-24S,25-diol (1) and 29-acetoxy-3beta
      methoxyserrat-14-en-21alpha-ol (2) on the basis of spectroscopic evidence. Some
      of these triterpenes were tested for the inhibitory effect on DNA topoisomerase
      II activity. Compound 1 showed a slightly less potent inhibitory activity with an
      IC(50) value of 186 microM.

PMID- 11582547
TI  - Identification and determination of oligomeric stilbenes in the roots of Caragana
      species by capillary electrophoresis.
AB  - A method based on capillary electrophoresis with electrochemical detection (CE
      ED) was employed for the determination of one alkaloid (hypaphorine) and the four
      oligomeric stilbenes, pallidol, kobophenol A, miyabenol C and (+)-alpha-viniferin
      in the roots of Caragana species. The five analytes could be well separated
      within 12 min in a 40 cm length capillary at a separation voltage of 12 kV in a
      100 mmol/L borate buffer (pH 10.0). The response was linear over about 3 orders
      of magnitude for all investigated analytes with detection limits (S/N = 3)
      ranging from 0.0385 to 0.111 mg/L. The five constituents presented in Caragana
      sinica can also be detected in the roots of other Caragana species, but their
      contents were quite different. It is demonstrated that CE-ED is a useful
      technique for the investigation of some electroactive constituents in plants.

PMID- 11582548
TI  - Examination of lectins, polysaccharopeptide, polysaccharide, alkaloid, coumarin
      and trypsin inhibitors for inhibitory activity against human immunodeficiency
      virus reverse transcriptase and glycohydrolases.
AB  - A variety of lectins were tested in vitro for inhibitory action against the
      activities of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase
      and the N-glycohydrolases (alpha-glucosidase, beta-glucosidase and beta
      glucuronidase). Lectins from Phaseolus vulgaris, Momordica charantia, Ricinus
      communis and its constituent chains, and Agaricus bisporus were able to inhibit
      HIV-1 reverse transcriptase. P. vulgaris lectin and A. bisporus lectin were the
      most potent. The aforementioned lectins had only weak or no inhibitory effects on
      the glycohydrolases. The inhibitory effect of polysaccharopeptide from the
      mushroom Coriolus versicolor on HIV-1 reverse transcriptase and alpha-glucosidase
      was enhanced after chemical modification with chlorosulfonic acid. However, the
      inhibitory effect of the algal polysaccharide fucoidan on HIV-1 reverse
      transcriptase and alpha-glucosidase was not augmented by sulfation. Trypsin
      inhibitors from Phaseolus lunatus and Glycine max, gossypol and alkaloids from
      Corydalis yanhusuo were able to inhibit HIV-1 reverse transcriptase. Dicoumarol
      was capable of inhibiting HIV-1 reverse transcriptase, alpha-glucosidase, beta
      glucosidase and beta-glucuronidase.

PMID- 11582549
TI  - Cytotoxicities and anti-herpes simplex virus activities of diterpenes isolated
      from Euphorbia species.
AB  - The cytotoxicities of nine diterpene polyesters obtained from Euphorbia species
      were assayed by measuring their effects on the growth of Vero cells. Their
      antiviral effects on the multiplication of Herpes simplex virus type 2 (HSV-2)
      were studied by using the virus yield reduction method in cell cultures. With the
      exception of the strongly cytotoxic 2alpha,5alpha,14beta-triacetoxy-3beta
      benzoyloxy-8alpha,15beta-dihydroxy-7beta-isobutanoyloxy-9alpha
      nicotinoyloxyjatropha-6(17),11E-diene (CC(50) 3.5 microg/ml), all the tested
      diterpenes exhibited a pronounced or moderate anti-herpes virus effect (IC(50)
      values between 2.5 and 8.3 microg/ml). The observed HSV-2 inhibitory activities
      were not associated with virucidal effects.

PMID- 11582550
TI  - New coumarins from Pterocaulon polystachyum.
AB  - Aerial parts of Pterocaulon polystachyum from Chaco province, Argentina, afforded
      the known coumarins ayapin, isoscopoletin, prenyletin, prenyletin methyl ether,
      virgatenol, obtusinin, 5-methoxy-6,7-methylenedioxycoumarin, 5-(3,3
      dimethylallyloxy)-6,7-methylenedioxycoumarin, 5-(2',3'-dihydroxy-3
      methylbutanoxy)-6,7-methylenedioxycoumarin, haplopinol methyl ether, 6-(1,1
      dimethyl-2-propenyl)-7-hydroxycoumarin and demethylnieshoutin; the last two are
      new as natural products while the five new coumarins from the collection were
      isovirgatenol, 3'-deoxyobtusinin, 6-methoxy-7-(2'-hydroxyethoxy)-coumarin, 5-(2'
      hydroxyethoxy)-6,7-methylenedioxycoumarin and a substance tentatively identified
      as 5-hydroxy-6,7-methylenedioxy-8-(3,3-dimethylallyl)-coumarin.

PMID- 11582551
TI  - Geranins C and D, additional new antiprotozoal A-type proanthocyanidins from
      Geranium niveum.
AB  - Two new additional A-type proanthocyanidins have been isolated from Geranium
      niveum. Their structures were determined by spectroscopic, chemical and
      chiroptical methods as epi-afzelechin-(4beta-->8,2beta-->O-->7)-gallocatechin (1)
      and epi-afzelechin-(4beta-->8,2beta-->O-->7)-afzelechin-(4beta-->8,2beta-->O-->7)
      afzelechin (2). Proanthocyanidins 1 and 2 were given the trivial names of
      geranins C and D, respectively. Compound 2 showed moderate antiprotozoal activity
      against Entamoeba histolytica and Giardia lamblia, whereas 1 exhibited weak
      activity toward E. histolytica.

PMID- 11582552
TI  - Separation and quantification of the major daucane esters of Ferula hermonis by
      HPLC.
AB  - A simple HPLC method was developed to quantify the major daucane sesquiterpene
      esters present in herb and roots of Ferula hermonis Boiss. The method utilized a
      C(18) reversed phase analytical column with isocratic elution for 30 minutes and
      UV detection at 240 nm. Extracts from two crude plant samples and two commercial
      products were fingerprinted and quantitatively analyzed.

PMID- 11582553
TI  - Sterols, triterpenes and biflavonoids of Viburnum jucundum and cytotoxic activity
      of ursolic acid.
AB  - The triterpenes ursolic acid (1), 27-p-Z-coumaroyloxyursolic acid (2), 27-p-E
      coumaroyloxyursolic acid, alpha-amyrine-3-palmitate and lupeol-3-palmitate were
      isolated through a bioactivity-guided fractionation from the acetonic extract of
      the aerial parts of Viburnum jucundum Morton in addition to amentoflavone, an
      epimeric mixture at C-2 of 2,3-dihydroamentoflavone, beta-sitosterol and beta
      sitosteryl glucopyranoside. Ursolic acid (1) was the only constituent that
      exhibited cytotoxic activity toward three human cancer cell lines in culture.
      This is the first phytochemical and cytotoxic analysis performed to this plant
      species.

PMID- 11582554
TI  - [German as a language of science in the 20th century].

PMID- 11582555
TI  - [Navigation systems for image-guided therapy: A review].
AB  - Navigation systems for image-guided therapy: A review. Navigation is visually
      interactive targeting based on the simultaneous display of instrument position
      and of the corresponding two- or three-dimensional image data sets. In this way
      it unifies anatomic information and therapeutic action. Medical navigation
      systems (MNS) can simulate realtime image guidance and thereby reduce radiation
      exposure as well as provide the full range of digital image processing during an
      intervention. Navigation is based on the tracking of medical instruments in space
      and the transformation of image, patient, and instrument coordinates into a
      common reference system. If the patient coordinate system is used as the common
      base, the process is called patient-based navigation (PBN). If, however, the
      imaging modality is present in the interventional suite and its reference system
      is used, modality-based navigation (MBN) results. MBN does not need pre
      interventional registration and inherently provides intra-operative imaging. In
      neurosurgery MNS's have been well established since years. They are in use for
      frameless biopsies and for minimizing the access morbidity in deeply situated
      pathologies. Currently there is a fast expansion of navigation into other
      surgical disciplines, e.g., orthopaedic surgery. The clinical accuracy of an MNS
      is hard to determine since an independent method of measurement is mostly not
      available during surgery. Normally, a deviation of below one up to about 5 mm
      between the display of the MNS and the actual position of an anatomic structure
      is reported. So far there have been only very few prospective randomized clinical
      trials between conventional and navigated interventions.

PMID- 11582556
TI  - Dark lumen MR-colonography: initial experience.
AB  - PURPOSE: The aim of this study was to assess a new strategy of MR colonography
      for the detection of colonic polyps/malignancy. The technique is based on a
      rectal enema with water in combination with the intravenous application of a
      paramagnetic contrast agent. METHODS: Twelve subjects were included in this study
      either due to suspected colorectal tumors or for screening purposes. For MR
      colonography the colon was filled with approximately 3000 ml of tap water while
      Gadobenate dimeglumine (0.2 mmol/kg) was injected intravenously. A T1w GRE
      sequence was acquired before and 75 sec after the contrast administration only in
      prone position. Three patient underwent the "bright lumen" MRC as well. All MR
      examinations were performed at least five days prior to conventional colonoscopy
      and the results of both modalities were compared. RESULTS: The colonic filling
      with water resulted in a homogeneously low signal throughout the colonic lumen in
      all twelve subjects. Intravenous injection of gadolinium caused avid enhancement
      of the colonic wall. Similarly lesions arising from the colonic wall enhanced
      avidly. Dark lumen MR colonography correctly identified five polyps in four
      patients. Bright lumen MRC showed in one patient false positive results.
      CONCLUSION: The new MR colonography concept based on a dark colonic lumen and a
      bright, contrast enhanced colonic wall turned out to be a promising alternative
      to the traditional MRC based on a bright lumen concept. The new technique
      suggests a higher accuracy in detecting polyps, a better evaluation of other
      parenchymal organs as well as a reduced time needed for data acquisition and
      analysis.

PMID- 11582557
TI  - [2D-phase contrast flow evaluation and contrast-enhanced MR angiography for
      perioperative assessment of internal mammary artery grafts].
AB  - PURPOSE: To evaluate LV functional parameters, graft flow and patency in patients
      with IMA grafts using a combined MR protocol with phase-contrast technique and
      contrast enhanced MR angiography. MATERIAL AND METHODS: Using a 1.5 T MR system
      27 patients with 27 left internal mammary artery (LIMA) and 41 venous grafts were
      examined before and 6 months after CABG surgery. A T(1)w-TSE sequence (slice
      thickness 5 mm) was applied for morphological imaging. LV function (EF, CO) was
      evaluated on cine images (segmented FLASH 2D, TR(eff) 11 ms, TE 4.8 ms, flip
      angle 25 degrees ). A phase-contrast FLASH 2D (TR 24 ms, TE 5 ms, flip angle 20
      degrees ) sequence was applied for aortic and IMA flow measurements.
      Postoperatively, a contrast enhanced FLASH 3D MR angiography (TR 3.8 ms, TE 1.4
      ms, flip angle 30 degrees ) with 25 ml Gd-DTPA was performed to assess bypass
      patency. RESULTS: In patients with reduced LV function (ejection fraction < 50 %)
      an improvement of the ejection fraction from 38.4 +/- 10.3 % to 49.8 +/- 15.3 %
      (p < 0.05) was found postoperatively. LIMA grafts were occluded in 1/27 patients,
      while 6/41 venous grafts were occluded. Distal LIMA anastomoses were demonstrated
      in 33 % by MRA. Flow of LIMA decreased from 21.2 +/- 11 ml/min/m(2)
      preoperatively to 14.4 +/- 9.6 ml/min/m(2) postoperatively (p < 0.01).
      CONCLUSION: MR imaging allows accurate combined assessment of LV function, bypass
      patency and flow. The protocol of this study may be applicable for perioperative
      follow-up studies in patients after CABG surgery.

PMID- 11582558
TI  - [Evaluation of left ventricular aneurysms before and after surgery using Cine
      MRI].
AB  - PURPOSE: To demonstrate the usefulness of cine-MRI for the evaluation of apical
      left ventricular aneurysms (ALVA) and for prediction of the surgical outcome.
      MATERIALS AND METHODS: We investigated 28 patients with ALVA, 13 of them
      additionally after aneurysmectomy at 1.5 T; 15 healthy volunteers served as
      normal controls. For cine-MRI k-space segmented Fl-2D-GE sequences were used.
      Analysis comprised the calculation of cardiac volume indices, cardiac function,
      and percentual myocardial thickening (PMT). For prediction of surgical results we
      divided left ventricle into an aneurysmatic and a non-aneurysmatic part. The non
      aneurysmatic part was assumed as the left ventricle after surgical remodelling.
      RESULTS: Enddiastolic and endsystolic volume indices (EDVIs and LV-ESVIs) were
      higher in patients with ALVA (123.7 +/- 30.2 ml/m(2), 94.3 +/- 32.5 ml/m(2),
      respectively) than in volunteers (79.1 +/- 13.9 ml/m(2), 25.5 +/- 5.1 ml/m(2),
      respectively) (p < 0.001). Stroke volume index (SVIs), cardiac index (CIs) and
      ejection fraction (EFs) were significantly lower in patients (30.4 +/- 9.1 vs.
      54.2 +/- 0.2 ml/beat/m(2); 2.2 +/- 0.8 vs. 3.9 +/- 0.9 l/min/m(2), 26.0 +/- 9.7
      vs. 67.9 +/- 4.5 %, respectively) (p < 0.001). There was a significant decrease
      of LV-EDVIs and LV-ESVIs (102.8 +/- 30.3 ml/m(2), 66.3 +/- 28.0 ml/m(2),
      respectively) (p = 0,002, p < 0.001, respectively), no change of SVIs (36.4 +/-
      6.0 ml/beat/m(2)) (p > 0.05) and a significant increase of CIs and EFs (3.0 +/-
      0.6 l/min/m(2), 37.91 +/- 10.15 %, respectively) (p < 0.001) after surgery. We
      found a good correlation between the preoperatively calculated (32.6 +/- 10.1 %)
      and the measured EF after surgery (37.9 +/- 9.8 %) (r = 0.70; p = 0.035). PMT was
      significantly lower in patients than in volunteers (median 11.9 +/- 10.7 vs. 70.2
      +/- 13.9 %; p < 0.001), especially in the aneurysmatic parts of left ventricle
      (median - 6.8 %; p < 0.001). CONCLUSION: Cine-MRI offers accurate evaluation of
      ALVA and enables preoperative estimation of left-ventricular volumes after
      surgery.

PMID- 11582559
TI  - [B-Flow: sonographic assessment and therapy for femoral artery pseudoaneurysm].
AB  - PURPOSE: To evaluate the diagnostic accuracy of femoral artery pseudoaneurysm by
      B-flow, a new ultrasound method and the outcome of compression treatment.
      MATERIAL AND METHODS: 700 patients with radiological interventions (300 DSA, 355
      PTA, 45 thrombolysis) have been examined by vascular ultrasound for possible
      bleeding at the puncture site to rule out pseudoaneurysms. The new B-flow
      ultrasound with a multi-frequency probe was used besides color-coded Doppler
      (CCD) and power Doppler (PD). RESULTS: No pseudoaneurysm was found in patients
      with diagnostic angiography and thrombolysis. In 25 of 355 patients a
      pseudoaneurysm was detected after PTA in 8 of them in the common and in 17 in the
      superficial femoral artery. The diameters were 1.5 to 4.5 cm, 3 cm on average. By
      ultrasound compression treatment of 20 minutes on the average 23 out of 25
      pseudoaneurysms were occluded without any further complication. In B-flow the
      lesion of the vessel wall, the flow in the fistula and in the sack of the
      pseudoaneurysm were better demonstrated and without artifacts compared to both
      other methods. This makes treatment by compression much easier, first of all
      because remaining flow phenomena and the progression of intracavitary thrombosis
      can be controlled. CONCLUSION: The newly developed B-flow detects both slow and
      fast flow phenomena. Visualisation of the fistula canal and the aneurysm sack is
      more reliable and examiner-independent than other Doppler methods such as CCD and
      PD. This allows better compression treatment of the fistula canal.

PMID- 11582560
TI  - [MR-venography using manual flow augmentation in an open low field MR system].
AB  - OBJECTIVE: To evaluate the feasibility of signal enhancement in the deep veins by
      means of manual compression of the calf (flow augmentation) as a new approach to
      MR venography in open configuration, low-field systems. METHODS: 10 healthy
      volunteers underwent MR venography of the calf unconstrained and during short
      localized manual compression. Gradient recalled echo sequences (FLASH, FISP) with
      repeated single slice acquisition and first-order gradient motion refocussing
      were tested in four protocols with and without arterial presaturation slabs (scan
      time 2.2 - 5.0 s per slice). The effect on flow enhancement was rated by means of
      a signal score. Interventional accessories, particularly an in-room LCD screen,
      were required for interactive application of compression manoeuvres. RESULTS:
      Sequences with arterial presaturation slabs were superior to those without
      regardless of the longer acquisition times. Careful targeting of compression to
      the mid-time of data acquisition was crucial to obtain marked flow acceleration.
      Enhancement was best in the case of proximally applied calf compression. Signal
      improvement was consistently achieved in the proximal parts of the posterior
      tibial and peroneal veins, but was only seen in 4/10 volunteers in the distal
      part of the anterior tibial vein. CONCLUSION: Flow augmentation by means of
      manual calf compression is a simple and effective complementary approach to MR
      venography in open configuration, low field MR systems.

PMID- 11582561
TI  - [Multidetector-row CT of the lungs: Multiplanar reconstructions and maximum
      intensity projections for the detection of pulmonary nodules].
AB  - PURPOSE: The present study was performed to evaluate the utility of axial,
      coronal and sagittal multiplanar reformations (MPR) and maximum intensity
      projections (MIP) in the detection of pulmonary nodules as compared to axial
      standard reconstructions (SR). MATERIALS AND METHODS: 103 patients with suspicion
      or evidence of pulmonary nodules underwent multidetector-row computed tomography
      (MDCT; Somatom plus 4 Volume Zoom, Siemens, Germany) of the chest in a single
      breath-hold technique. The raw data were acquired with a collimation of 1 mm and
      a pitch of 6 and underwent reconstruction with 0.6 mm increment. MPR and MIP in
      three planes [5 mm slice thickness (SL), 4 mm increment] were calculated from the
      raw data and compared to axial SR (5 mm SL). Three blinded observers evaluated
      the number, size and the quality of depiction of pulmonary nodules according to a
      3-point confidence scale (1 = certain, 2 = probable, 3 = uncertain). Four patient
      groups were formed using the axial SR. Group 1 presenting no nodules, group 2
      presenting probable nodules and group 3 presenting definitively lung nodules.
      Patients with more than 7 pulmonary nodules (group 4) were not included in the
      study. The 1 mm slice was used as the gold standard. RESULTS: Inter-observer
      correlation was good at r = 0.77. MIP were superior in the depiction of pulmonary
      nodules at a statistically significant level of p < 0.05 (mean values in group 3
      = 2.58 to 1.97 and group 2 = 0.99 to 0.79 with MIP and SR, respectively). In four
      patients 6 additional lesions were identified with MIP that were missed with
      axial SR. Overall, with SR 72 nodules, with MPRs 78, and with MIPs 99 nodules
      were delineated. Pulmonary nodules larger than 5 mm in size were equally well
      depicted with both modalities, whereas lesions smaller than 5 mm in size were
      significantly better depicted with MIP (p < 0.05). Diagnostic confidence for all
      lesions was highest with MIP and least with SR. CONCLUSION: MIP reformations on
      the basis of MDCT data sets are superior in the depiction and diagnosis of
      pulmonary nodules as compared to axial standard reconstructions and MPR.

PMID- 11582562
TI  - [Acute or chronic transplant rejection - high resolution CT of the chest in lung
      transplant recipients].
AB  - PURPOSE: Aim of the study was to evaluate the postoperative changes in patients
      with single (SLTX) or double lung transplantation (DLTX) with HRCT and to
      correlate those findings with the clinical diagnosis. MATERIAL AND METHODS: 29
      patients with SLTX (n = 14) or DLTX (n = 15) were observed for more than 6 years
      after transplantation by HRCT (n = 82). CT examinations were performed in
      inspiration and expiration (n = 70) with a slice thickness of 1 mm and a feed of
      10 mm. The image material was evaluated by 2 experienced radiologists in
      consensus. Criteria for acute rejection at HRCT were: ground glass opacities and
      focal air trapping in expiration. Criteria for chronic transplant rejection were:
      bronchial dilatation, bronchial wall thickening and thickening of interlobar
      septae. The clinical evaluation consisted of laboratory tests, lung function
      tests, and bronchoscopy including bronchial lavage in special cases. RESULTS:
      20/29 patients are still alive (mean 21 months). 5/9 patients died because of
      chronic transplantant rejection, 1 patient suffered from a non-Hodgkin's lymphoma
      localised at the right hilus. Severe threatening pneumonia occurred in 13 cases.
      10/29 patients showed symptoms of acute rejection. Expiratory HRCT found a focal
      air trapping in all cases and extended ground glass opacities in 11/14 cases.
      Also a bronchial dilatation was observed in more than 50 % (9/14). 12/29 patients
      suffered from chronic transplant rejection. HRCT showed bronchial dilatation in
      26/27 investigations and severe ground glass opacities in 21/27 investigations.
      Thickening of the interlobal septa as well as centrilobular opacities were found
      in more than 50 % of the examinations. CONCLUSION: High resolution CT of the
      chest in patients after lung transplantation is able to show numerous
      pathological alterations. Without clinical information a confident
      differentiation in acute or chronic transplant rejection or pneumonia can be
      difficult or impossible.

PMID- 11582563
TI  - [A software tool for automatic image-based ventilation analysis using dynamic
      chest CT-scanning in healthy and in ARDS lungs].
AB  - PURPOSE: Density measurements in dynamic CT image series of the lungs allow one
      to quantify ventilated, hyperinflated, and atelectatic pulmonary compartments
      with high temporal resolution. Fast automatic segmentation of lung parenchyma and
      a subsequent evaluation of it's respective density values are a prerequisite for
      any clinical application of this technique. MATERIAL AND METHODS: For automatic
      lung segmentation in thoracic CT scans, an algorithm was developed which uses (a)
      different density masks, and (b) anatomic knowledge to differentiate heart,
      diaphragm and chest wall from ventilated and atelectatic lung parenchyma. With
      Animal Care Committee approval, the automated technique was tested in 8
      anaesthetized ventilated pigs undergoing dynamic CT before and after induction of
      lavage-ARDS. Images were acquired in one supradiaphragmatic, cross-sectional
      slice (temporal resolution of 100 ms; slice thickness of 1 mm, high resolution
      reconstruction algorithm). In 120 CT images the total pixel number and the
      calculated MLD from the automatically segmentated lung were compared to the
      values obtained from an interactive lung segmentation. RESULTS: The software tool
      was able to read all image series (DICOM standard). Automatic and interactive
      segmentation were in high agreement (R(2) = 0.99 for the total number of pixels
      and the MLD). Originally, the most frequent error was misclassification of
      atelectasis as extrapulmonary solid tissue. CONCLUSION: An automatic software
      tool is presented for lung segmentation in healthy lungs and in ARDS. Aerated
      lung and atelectasis were identified with high accuracy. This post-processing
      tool allows for a quantitative, CT based assessment of ventilation and
      recruitment processes in the lung. Thus, it may help to optimize ventilation
      patterns in patients with ARDS.

PMID- 11582564
TI  - [First results in an animal model on stents sheathed with a
      polytetrafluoroethylene membrane].
AB  - OBJECTIVES: Mechanisms of restenosis after coronary stent implantation include
      marked intimal proliferation as well as vascular tissue protrusion through the
      meshes. Thus, stent sheathed with membranes may be an alternative to improve the
      long-term outcome. METHODS: Seventeen cylindric serpentine shaped 316L stainless
      steel stents (nominal diameter 3.0 mm, length 15 mm) lined and covered by a
      polytetrafluoroethylene (PTFE) membrane and 10 unsheathed devices were implanted
      into the iliac arteries of 14 New Zealand White Rabbits for an observation period
      of 1 - 10, 11 - 20, and 21 - 30 weeks. After sacrificing the animals, specimens
      were harvested, fixed in formalin, processed in paraffin, serially sliced into 5
      microm thick preparations, and stained (hematoxylin & eosin, elastica von
      Gieson). RESULTS: The polytetrafluoroethylene membrane stents increased the
      vascular lumen significantly (p < 0.04) to 1185.3 - 1620.4 microm compared with
      the native segments (655.6 +/- 268.8 microm). In the stainless steel stents the
      lumen decreased from 1873.1 microm to 719.1 microm. None of the devices
      penetrated the internal elastic membrane. There was no inflammatory vascular
      reaction. Compared to the native segments, the amount of elastic fibres was
      slightly less (native: 8.9 %, PTFE: 2.3 - 3.5 %, without PTFE: 1.9 - 5.5 %)
      whereas the collagen fibres increased marginally (native: 5.1 %, PTFE: 6 - 6.9 %,
      without PTFE: 6.4 - 8.4 %). CONCLUSIONS: In the rabbit iliac artery, stents
      sheathed with a microporous polytetrafluoroethylene membrane showed good tissue
      compatibility with no restenosis. These results warrant clinical trials.

PMID- 11582565
TI  - [Experimental evaluation of vessel diameter from 0.3 to 8 mm in CE MR
      angiography].
AB  - PURPOSE: To evaluate the detection rate of vascular stenosis in contrast-enhanced
      3D MR angiography using a flow phantom. MATERIAL AND METHODS: The examinations
      were performed on a 1.5 T whole body imaging system (Magnetom Symphony/Quantum)
      with 30 mT/m gradient field strength using a body-phased-array coil. Different 3D
      sequences (TR/TE/FA < 5 ms/< 2 ms/25 degrees ) with slice thicknesses ranging
      from 0.67 to 1.25 mm were applied. A gelantine-filled plastic cylinder with PVC
      tubes of 8 mm diameter was used as a vascular phantom. The tubes had concentric
      and excentric stenoses (50 - 90 %) of different lengths. For the detection of
      different vessel diameters another phantom with 0.3 - 8 mm silicon tubes was
      used. Both systems were flushed with a solution of Gd-DTPA (0.15 mmol/l) and
      saline at flow rates from 50 to 200 cm/s. The phantoms were positioned 0 degrees,
      45 degrees, and 90 degrees towards the z-axis. RESULTS: The degree of stenosis
      was under- and overestimated in less than 10 %. The sequence with the highest
      spatial resolution provided the best results. Detection and evaluation of tubes
      >/= 2 mm proved to be reliable. CONCLUSION: Contrast-enhanced 3D MR angiography
      provides an almost exact evaluation of the degree of stenosis in the phantom
      study. Evaluation of vessel diameters < 2 mm is not possible.

PMID- 11582566
TI  - [Aneurysma spurium of the ascending aorta with secondary perforation into the
      right ventricle].

PMID- 11582567
TI  - [Rhombencephalosynapsis as a rare anomaly of the posterior skull base].

PMID- 11582568
TI  - [Hemosiderosis of the central nervous system due to recurrent subarachnoid
      hemorrhage in myxopapillary ependymoma of the cauda equina].

PMID- 11582569
TI  - Frequency of XY sperm increases with age in fathers of boys with Klinefelter
      syndrome.
AB  - With increasing availability of drugs for impotence and advanced reproductive
      technologies for the treatment of subfertility, more men are fathering children
      at advanced ages. We conducted a study of the chromosomal content of sperm of
      healthy men aged 24-57 years to (a) determine whether father's age was associated
      with increasing frequencies of aneuploid sperm including XY, disomy X, disomy Y,
      disomy 21, and sperm diploidy, and (b) examine the association between the
      frequencies of disomy 21 and sex-chromosomal aneuploidies. The study group
      consisted of 38 fathers of boys with Klinefelter syndrome (47, XXY) recruited
      nationwide, and sperm aneuploidy was assessed using multicolor X-Y-21 sperm FISH
      ( approximately 10,000 sperm per donor). Paternal age was significantly
      correlated with the sex ratio of sperm (Y/X; P=.006) and with the frequency of XY
      sperm (P=.02), with a clear trend with age by decades (P<.006). Compared with
      fathers in their 20s (who had an average frequency of 7.5 XY sperm per 10,000),
      the frequencies of XY sperm were 10% higher among fathers in their 30s, 31%
      higher among those in their 40s, and 160% higher among those in their 50s (95% CI
      69%-300%). However, there was no evidence for age effects on frequencies of sperm
      carrying nullisomy sex; disomies X, Y, or 21; or meiosis I or II diploidies. The
      frequencies of disomy 21 sperm were significantly associated with sex-chromosomal
      aneuploidy (P=.04)-in particular, with disomy X (P=.004), but disomy 21 sperm did
      not preferentially carry either sex chromosome. These findings suggest that older
      fathers produce higher frequencies of XY sperm, which may place them at higher
      risk of fathering boys with Klinefelter syndrome, and that age effects on sperm
      aneuploidy are chromosome specific.

PMID- 11582571
TI  - Crystal structure of the W35A mutant thioredoxin h from Chlamydomonas
      reinhardtii: the substitution of the conserved active site Trp leads to
      modifications in the environment of the two catalytic cysteines.
AB  - The conformational analysis of W35A thioredoxin h from the eukaryotic green alga
      Chlamydomonas reinhardtii in the solid state has been carried out by x-ray
      diffraction, with the aim to clarify the role of Trp in the catalysis.
      Comparative analysis of W35A mutant with wild-type (WT) thioredoxin shows that,
      even if the structural motif of thioredoxin is not perturbed, the substitution of
      Trp35 by an Ala leads to significant changes in protein conformation near the
      active site. This rearrangement increases its solvent exposure and explains the
      change of the pKa values of the catalytic cysteines. The substitution of the Trp
      residue also influences the crystal packing as well as the recognition ability of
      thioredoxin. The solid state analysis suggests that the Trp residue has a
      structural function both to force the active site in the bioactive conformation,
      and to mediate the protein-protein recognition.

PMID- 11582570
TI  - Phylogenetic and familial estimates of mitochondrial substitution rates: study of
      control region mutations in deep-rooting pedigrees.
AB  - We studied mutations in the mtDNA control region (CR) using deep-rooting French
      Canadian pedigrees. In 508 maternal transmissions, we observed four substitutions
      (0.0079 per generation per 673 bp, 95% CI 0.0023-0.186). Combined with other
      familial studies, our results add up to 18 substitutions in 1,729 transmissions
      (0.0104), confirming earlier findings of much greater mutation rates in families
      than those based on phylogenetic comparisons. Only 12 of these mutations occurred
      at independent sites, whereas three positions mutated twice each, suggesting that
      pedigree studies preferentially reveal a fraction of highly mutable sites.
      Fitting the data through use of a nonuniform rate model predicts the presence of
      40 (95% CI 27-54) such fast sites in the whole CR, characterized by the mutation
      rate of 274 per site per million generations (95% CI 138-410). The corresponding
      values for hypervariable regions I (HVI; 1,729 transmissions) and II (HVII; 1,956
      transmissions), are 19 and 22 fast sites, with rates of 224 and 274,
      respectively. Because of the high probability of recurrent mutations, such sites
      are expected to be of no or little informativity for the evaluation of mutational
      distances at the phylogenetic time scale. The analysis of substitution density in
      the alignment of 973 HVI and 650 HVII unrelated European sequences reveals that
      the bulk of the sites mutate at relatively moderate and slow rates. Assuming a
      star-like phylogeny and an average time depth of 250 generations, we estimate the
      rates for HVI and HVII at 23 and 24 for the moderate sites and 1.3 and 1.0 for
      the slow sites. The fast, moderate, and slow sites, at the ratio of 1:2:13,
      respectively, describe the mutation-rate heterogeneity in the CR. Our results
      reconcile the controversial rate estimates in the phylogenetic and familial
      studies; the fast sites prevail in the latter, whereas the slow and moderate
      sites dominate the phylogenetic-rate estimations.

PMID- 11582572
TI  - Crystal structure of a collagen-like polypeptide with repeating sequence Pro-Hyp
      Gly at 1.4 A resolution: implications for collagen hydration.
AB  - The use of polypeptide models has proved to be a valuable tool to obtain accurate
      information on the collagen triple helix. Here we report the high resolution
      crystal structure of a collagen-like polypeptide with repeating sequence Pro-Hyp
      Gly. The structure has been refined to an R(factor) of 0.137 and an R(free) of
      0.163 using synchrotron diffraction data extending up to 1.4 A resolution. The
      polypeptide triple-helical structure binds a large number of water molecules, in
      contrast with a previous structure determination at lower resolution. The highly
      hydrated nature of this polypeptide confirms a number of previous studies
      conducted both in solution and in the crystal state. In addition, neighboring
      polypeptide triple helices are directly bound in the crystal through Hyp-Hyp
      hydrogen-bonding interactions. This finding supports the idea that Hyp residues
      may be important for the assembly of the triple helices in the collagen fibrils
      and may stabilize the fibrils by mediating direct contacts between neighboring
      molecules.

PMID- 11582573
TI  - Formation of an RNase A derivative containing an aminosuccinyl residue in place
      of asparagine 67.
AB  - At acidic pH, Asp67 and beta-Asp67 (beta-Asp: isoaspartic acid residue)
      derivatives of RNase A, obtained by selective deamidation of the parent enzyme,
      spontaneously produces a new derivative containing an aminosuccinyl residue
      (Asu). The overall secondary structure of the protein chain does not change as a
      consequence of this substitution, while the catalytic activity on RNA is reduced
      to about 25%. The pH dependence of the first-order rate constants for the Asu
      formation has a bell-shaped profile, the maximum being close to the pK(a) of the
      aspartic acid side chains. Moreover, the values of the rate constants are of the
      same magnitude of those measured for Asp-containing peptides whose sequence
      mimics the Asu formation site of the enzyme. This feature indicates that Asp67
      and beta-Asp67 residues in the deamidated RNase A derivatives are sited in a
      region flexible enough to permit the cyclization of the carboxylic side chain to
      succinimide ring. These results are discussed at the light on to the three
      dimensional structure and the thermodynamic stability of the aspartic acid
      derivatives of RNase A.

PMID- 11582574
TI  - A three-residue cyclic scaffold of non-RGD containing peptide analogues as
      platelet aggregation inhibitors: design, synthesis, and structure--function
      relationships.
AB  - Antagonists of fibrinogen at the GPIIb/IIIa receptor, which is the most abundant
      membrane protein on the platelet surface, are under active investigation as
      potential antithrombotics. The critical interaction between GPIIb/IIIa and
      fibrinogen can be inhibited by either linear or cyclic RGDS-containing peptides,
      which have been proved as lead compounds in the design of platelet aggregation
      inhibitors. In this study we present the design and construction of a new class
      of cyclic (S,S) non-RGD containing peptide sequences, using two Cys as a
      structural scaffold for the development of antiaggregatory agents. The (S,S)-CDC-
      sequence was incorporated as a conformational constraint, in molecules bearing at
      least one positive charge with the general formula (S,S)XCDCZ, where X = Ac-Arg,
      Pro-Arg, Pro-Ser-Lys, and Pro-Ser-Arg, and Z = -NH(2) and Arg-NH(2).
      Investigation of the structure-function relationships was performed on the basis
      of (a) the local conformation induced by the (S,S)-CDC motif, (b) the distance of
      the positively (R-C(zeta) or K-N(zeta)) and negatively (D-C(gamma)) charged
      centers, (c) the presence of a second positive or negative charge on the
      molecule, and (d) the orientation of the basic and acidic side chains defined by
      the pseudo dihedral angle (Pdo), which is formed by the R-C(zeta), R-C(alpha), D
      C(alpha), and D-C(gamma) atoms in the case of (S,S)-RCDC and by the K-N(zeta), K
      C(alpha), D-C(alpha), and D-C(gamma) atoms in the case of (S,S)-KCDC.

PMID- 11582575
TI  - Conformation and calcium-binding properties of a bicyclic nonapeptide.
AB  - The conformation and calcium binding properties of the bicyclic nonapeptide BCP2,
      cyclo-(Glu(1)-Ala(2)-Pro(3)-Gly(4)-Lys(5)-Ala(6)-Pro(7)-Gly(8))-cyclo-(1gamma -->
      5epsilon) Gly(9), have been investigated by means of NMR spectroscopy.
      Interproton distances, evaluated by nuclear Overhauser effect (NOE) contacts, and
      straight phi angles, from (3)J(NH-alphaCH), have been used to obtain a feasible
      model for the BCP2-Ca(2+) (BCP: bicyclic peptide) complex by means of restrained
      molecular dynamics (RMD). The NMR analysis of the free peptide, carried out in
      CD(3)CN, shows the presence in solution of at least four conformers in
      intermediate exchange rate. The addition of calcium ions caused the appearance of
      a new set of resonances, differing from those observed for the free BCP2. A
      comparison with published data about the conformational behavior of the closely
      analogous peptide BCP3, differing from BCP2 for two Leu residues instead of two
      Ala residues in positions 2 and 6, shows that this simple substitution
      dramatically increases the peptide flexibility. On the contrary, upon calcium ion
      addition, both BCP2 and BCP3 reach a strictly close conformation, as strongly
      testified by the almost identical (1)H-NMR spectra exhibited by both peptides.
      The RMD molecular model of the BCP2-Ca(2+) complex, here reported, is a quite
      symmetric structure, presenting a three-dimensional cavity ideal for the binding
      of spherical cations. Four carbonyls from the main ring (Ala(2), Gly(4), Ala(6)
      and Gly(8)) point toward it, offering, together with the two carbonyls of the
      peptide bridge (Gly(9) and gammaGlu(1)), putative coordinations to the cation.

PMID- 11582576
TI  - Design, synthesis, and conformational study of biologically active photolabeled
      analogues of the main immunogenic region of the acetylcholine receptor.
AB  - Photoaffinity labeling is a powerful tool for the characterization of the
      molecular basis of ligand binding to acceptor molecules, which provides important
      insights for mapping the bimolecular interfaces. The autoimmune disease
      myasthenia gravis is caused by autoantibodies against the acetylcholine receptor
      (AChR). The majority of the anti-AChR antibodies bind to the "main immunogenic
      region" (MIR) of the AChR. To identify the contact points between the
      complementarity determining regions of the anti-MIR antibodies that recognize the
      MIR contact sites of the AChR, we present here three photoreactive dodecapeptide
      MIR analogues containing the photolabel p-benzoyl-L-phenylalanine (Bpa) moiety,
      either in position 1 or 11. The structure of the produced 12-mers was analyzed
      using two-dimensional (1)H-NMR spectroscopy, whereas their binding to anti-MIR
      monoclonal antibodies (mAbs) was determined by immunochemical assays. In all
      cases the modifications resulted in conservation of the beta-turn conformation of
      the N-terminus, which has been proved essential for antibody recognition and
      increased anti-MIR binding relative to the MIR decapeptide.

PMID- 11582577
TI  - Fluorescence studies on the binding between 1-47 fragment of cholecystokinin
      receptor CCK(A)-R(1-47) and nonsulfated cholecystokinin octapeptide CCK8.
AB  - The interaction between the 1-47 N-terminus fragment of the cholecystokinin
      receptor and the nonsulfated cholecystokinin octapeptide, CCK8, is monitored by
      fluorescence emission. Quenching of the fluorescence intensities is observed on
      binding. Dissociation constants calculated by these data are in the same
      submicromolar range as found for the binding of linear CCK8 analogues to B-type
      receptors. Although detailed structural information cannot be obtained,
      fluorescence emission is more sensitive than other techniques and permits fast
      detection of receptor-ligand interaction.

PMID- 11582578
TI  - An algorithm for evaluating the ethics of a placebo-controlled trial.
AB  - The purpose of this article is to clarify the decision points that are important
      to consider when evaluating the ethics of a placebo-controlled trial. The ethical
      requirements for research involving human subjects are reviewed, and the
      rationale for and potential problems with concomitant placebo control are
      explained. A series of case discussions are used to illustrate each decision
      point. The critical decision points in the evaluation of the ethics of a placebo
      controlled trial are as follows: (i) Is placebo being used in place of standard
      therapy? (ii) Is standard therapy likely to be effective? (iii) Is the toxicity
      of standard therapy such that patients routinely refuse this treatment? (iv)
      Could the use of placebo result in severe suffering or irreversible harm? (v) Is
      the variability in the placebo response such that it is reasonable to consider
      other options for the control group? (vi) Would a reasonable person with an
      average degree of altruism and risk aversiveness agree to participate in this
      study? The algorithm presented in this article gives researchers and research
      monitors (such as Institutional Review Board members) the tools they need to
      evaluate the ethics of a study that uses concomitant placebo control.

PMID- 11582579
TI  - Induction of interleukin-1beta and interleukin-6 mRNA by low doses of ionizing
      radiation in macrophages.
AB  - We have previously reported the antimetastatic effects and augmentation of immune
      responses, which would be a mechanism of the antimetastatic effects, of 0.1 to
      0.2 Gy total body irradiation. To elucidate the cellular mechanisms of the
      augmentation of immune response, we investigated the effects of low-dose
      irradiation on gene expression of interleukin-1beta (IL-1beta) and IL-6 using
      mouse peritoneal macrophages in vitro. Absolute mRNA quantification was carried
      out using competitive polymerase chain reaction. Gene expression of IL-1beta and
      IL-6 was increased 1 to 2 hr after 2.0 Gy irradiation and then decreased to below
      the basal expression level 4 hr after irradiation. Irradiation with 0.1 Gy
      increased IL-6 expression 2 hr after irradiation, but it did not affect IL-1beta
      expression. Downregulation of IL-1beta and IL-6 observed 4 hr after 2.0 Gy
      irradiation was not observed with 0.1 Gy irradiation. The protein kinase C (PKC)
      inhibitor H7 and the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor
      wortmannin inhibited induction of IL-1beta and IL-6 expression, which suggests
      that radiation-induced IL-1beta and IL-6 expression is achieved by PKC- and PI3
      kinase-mediated signaling.

PMID- 11582580
TI  - Evaluation of cell survival, DNA double strand breaks, and DNA synthesis during
      concurrent camptothecin and X-radiation treatments.
AB  - We evaluated cell survival, DNA double strand breaks (dsbs), and DNA synthesis
      following camptothecin (CPT) alone or concurrent CPT and X-radiation treatments
      in exponential-phase cultures of a radioresistant human melanoma cell line. Cell
      survival was measured by a clonogenic assay. DNA dsbs were measured by pulsed
      field gel electrophoresis. DNA synthesis was measured by incorporation of (3)H
      thymidine. We found that (i) concurrent CPT and X-radiation interacted
      additively, unlike previous results with plateau-phase cultures of these cells,
      which showed synergistic interaction; (ii) there were strong negative
      correlations (correlation coefficients of at least 0.82) between clonogenic
      surviving fractions and DNA dsbs following CPT alone or concurrent CPT and
      radiation treatments; and (iii) concurrent CPT and radiation (10 Gy) treatment
      did not completely inhibit DNA synthesis, even though addition of radiation to
      CPT did further decrease DNA synthesis (relative to CPT alone) at CPT
      concentrations below 20 microM. Our results suggest that during concurrent CPT
      and radiation treatment residual DNA dsb levels were good indicators of cell
      killing and that the absence of complete inhibition of DNA synthesis could at
      least in part explain the additive interaction between CPT and radiation.

PMID- 11582581
TI  - Chromosome 6p21.2, 18q21.2 and human papilloma virus (HPV) DNA can predict
      prognosis of cervical cancer after radiotherapy.
AB  - Loss of heterozygosity (LOH) is one of the most important mechanisms for
      inactivation of tumor-suppressor genes. Studies of LOH in patients with cervical
      carcinoma have reported a high frequency of LOH on 3p21.3, 6p21.2, 17p13.1, and
      18q21.2. Our study explored whether p53 status, human papilloma virus (HPV), and
      LOH on chromosome 3p21.3, 6p21.2, 17p13.1, and 18q21.2 are associated with
      treatment outcome in 65 patients with cervical cancer after radiotherapy. Tumors
      and normal DNA were analyzed by polymerase chain reaction (PCR) for genetic
      losses at 10 polymorphic microsatellite loci. The presence of HPV and its type
      were analyzed by PCR-based assay using the consensus primers for E6, E7, and L1
      region. Mutations of the p53 gene were identified by a single-strand conformation
      polymorphism analysis. Chromosomes 3p21.3, 6p21.2, 17p13.1, and 18q21.2 were
      involved in the LOH in 23.1%, 41.5%%, 33.8%, and 23.1% of the tumors in our
      study, respectively. HPV-positive tumors were found in 73.8% of the patients and
      p53 mutation in 10.8%. The patients with LOH on chromosome 6p21.2 and 18q21.2
      survived significantly shorter compared with those without LOH on chromosome
      6p21.2 and 18q21.2 in both the overall survival (P = 0.006 and P = 0.007) and the
      disease-free survival (P = 0.005 and P = 0.008). The HPV-negative patients
      survived significantly shorter compared with the HPV-positive patients in both
      the overall survival (P = 0.01) and the disease-free survival (P = 0.04).
      According to multivariate analysis, HPV status (P = 0.0004, P = 0.01), LOH on
      6p21.2 (P = 0.006, P = 0.02), and LOH on 18q21.2 (in both P = 0.01) is a
      significant predictor of both overall and disease-free survival time. The results
      of our study suggest that absence of HPV infection, LOH on 6p21.2, and LOH on
      18q21.2 are the most important determinants of outcome of patients with cervical
      carcinoma after radiotherapy.

PMID- 11582582
TI  - Healing of experimental colonic anastomoses: effects of combined preoperative
      high-dose radiotherapy and intraperitoneal 5-fluorouracil.
AB  - To study the effects of preoperative radiochemotherapy (RCT) on the healing of
      colonic anastomosis, the rectosigmoid colon in male Wistar rats was irradiated up
      to an end dose of 41.6 Gy (RT) or sham-irradiated (SR). During the last 5 days of
      the irradiation schedule, 5-fluorouracil (5-FU) was administered
      intraperitoneally in either a high dose (20 mg/kg, chemotherapy-high dose [CH])
      or a low dose (10 mg/kg, chemotherapy-low dose [CL]). Animals were randomly
      arranged into six groups: group I, control (SR + saline intraperitoneally); group
      II, RT only; group III, SR + CL; group IV, RT + CL; group V, SR + CH; group VI,
      RT + CH. Four days after RCT, a side-to-side anastomosis was constructed between
      the irradiated rectosigmoid and the nonirradiated caecum. Animals were killed 10
      days postoperatively. No significant differences were found in the anastomotic
      bursting pressure or the bursting wall tension. In group VI, mitoses were less (P
      < 0.01) and mucosal ulceration was more (P = 0.03) pronounced compared to group
      I. Sclerotic arteries were seen in all irradiated groups and in animals that
      received high-dose 5-FU alone. 5-FU administration in high or low dose, with or
      without RT, induced more inflammation in the submucosa compared to controls (P <
      0.05). Conclusively, RCT has no detrimental effect on the mechanical strength of
      colonic anastomosis in this rat model. However, RCT with high-dose 5-FU induces
      more histological alterations at the anastomotic site.

PMID- 11582583
TI  - Tumor apoptosis in cervical cancer: its role as a prognostic factor in 42
      radiotherapy patients.
AB  - To investigate tumor apoptosis as a prognostic factor for outcome following
      radiation therapy, comparisons were made of apoptotic index (AI) as a predictor
      of short- vs. long-term response and pretreatment vs. radiation-induced
      apoptosis. Forty-two patients with proven squamous cell carcinoma of the uterine
      cervix were treated by radiation alone. Apoptosis was measured by light
      microscopic observation of hematoxylin and eosin-stained sections from biopsies
      taken before treatment and 4 and 24 hr after 2 Gy. Patients were evaluated at the
      end of the external radiation for determination of short-term response and for
      long-term outcome as well (median follow-up of 27 months). Patients with high
      spontaneous AI showed poor short-term response, local control, and survival. The
      significance of AI as a predictor of short-term response was lost after allowing
      for differences in tumor size. The positive predictive value of AI for local
      control and survival was independent of tumor size and stage. High AI was
      associated with poor local control and long-term prognosis in advanced squamous
      cell carcinoma of the cervix. The in vivo radiation-induced AI after 4 or 24 hr
      did not predict radiation therapy outcome.

PMID- 11582585
TI  - Assessment of patient-independent intrinsic error for a noninvasive frame for
      fractionated stereotactic radiotherapy.
AB  - The purpose of our study was to examine the extent of patient-independent
      intrinsic error associated with multiple, repeat remounting of the Laitinen
      Stereoadapter. The Laitinen frame was repeatedly mounted on a solid water phantom
      and imaged using computed tomography (CT). The phantom contained five targets
      located in the center, anterior, right, left, and posterior orientations. The
      images were processed, fused, and analyzed on the Pinnacle 3-D treatment planning
      system. The coordinate values (in the x, y, and z directions) for each target
      were determined for each mounting, and an absolute mean deviation was calculated
      for 11 repetitions. The mean deviation in the x, y, and z direction for the
      central and right target, and in the x and y direction for the posterior and
      anterior target was less than 2.0 mm. However, the mean error in the z direction
      of the anterior and posterior targets was 1.79 +/- 1.02 mm and 2.20 +/- 1.32 mm,
      respectively. Rotational misalignment during repeat frame fixation contributed to
      the observed deviations and in particular affected the antero-posterior plane.
      With the exception of two occasions where an obvious mounting error occurred, a
      significant portion of error from remounting the Laitinen Stereoadapter is
      associated with the operator and the imaging process. The observation of an
      angular displacement around the axis through the earplugs suggests that a certain
      degree of rotational misalignment in daily remounting is possible. Targets in the
      antero-posterior plane are most susceptible to localization error as a
      consequence of rotational misalignment. In summary, the overall error is within
      the limits of current imaging technology but not within submillimeter accuracy.
      Clinical application should take these errors into consideration when designing
      field margins.

PMID- 11582584
TI  - Short-term sexual function after prostate brachytherapy.
AB  - Sexual function was evaluated in 34 patients with low-risk prostate cancer (PSA <
      or = 10, Gleason score < or = 6, clinical stage T1/T2) undergoing brachytherapy
      in a phase III prospective randomized trial comparing iodine-125 ((125)I) to
      palladium-103 ((103)Pd). The mean and median International Index of Erectile
      Function (IIEF) scores for the entire group were 14.2 and 16.5, respectively, and
      there was no difference between these scores when stratified by isotope. IIEF
      scores < 6, 6 to 11, and > or = 12 were recorded in 35% (12/34), 6% (2/34), and
      59% (20/34) of patients, respectively. Hematospermia, orgasmalgia (pain at the
      time of orgasm), and alteration in intensity of orgasm were documented in 26%
      (9/34), 15% (5/34), and 38% (13/34) of patients, respectively, but these side
      effects were of limited duration for most patients. There was no relationship
      between radiation dose to the neurovascular bundles (NVB), which averaged 209% of
      the prescribed prostate dose, and the development of postbrachytherapy impotence.
      All four impotent patients who used sildenafil responded favorably. With a median
      follow-up of 13 months, 65% of patients undergoing prostate brachytherapy
      maintained sexual function without pharmacologic support. Including sildenafil
      responses, 76.5% of patients sustained erections sufficient for sexual
      intercourse.

PMID- 11582586
TI  - Endothelin receptor antagonists in the treatment of prostate cancer.

PMID- 11582587
TI  - Repeated biopsies in evaluation of therapeutic effects in prostate carcinoma.
AB  - BACKGROUND: Apoptosis is one of the major events following total androgen
      blockade (TAB). The aim of this study was to determine the predictive value of
      some histological parameters including apoptosis and gene products which
      influence apoptosis, based on repeated biopsies taken from the same patients.
      METHODS: At the time of diagnosis by needle biopsy TNM stage, serum PSA,
      Gleason's grade, apoptotic and mitotic index, Ki67, p53, and bcl(2) expression
      were investigated in 60 prostate carcinoma patients. Antiandrogen therapy
      supplemented with surgical or chemical castration was administered. Serum PSA
      test and needle biopsy were repeated 13-14 weeks after starting the therapy,
      simultaneously with determination of the apoptotic and mitotic index, Ki67, p53,
      and bcl(2) expression. RESULTS: Forty-seven patients were alive at the end of the
      study, 13 patients died. Decrease in mitotic, increase in apoptotic index
      predicted favourable long-term response to antiandrogen therapy. Lower Ki67 and
      (mutant) p53 expression in the first and also in the second biopsy pointed to
      favourable effect of antiandrogen treatment. Since the ratio between Ki67 and
      apoptotic index strongly decreased in the survivors upon therapy, changes in
      Ki67/apoptosis ratio is recommended as a histologically detectable predictive
      factor. bcl(2) expression did not show significant correlation with the outcome
      of the disease. CONCLUSIONS: Histological evaluation of mitotic and apoptotic
      index, Ki67, and p53 expression in repeated biopsies contributes to predicting
      the value of the actual treatment and may be useful to institute alterations in
      therapy.

PMID- 11582588
TI  - Human glandular kallikrein 2 levels in serum for discrimination of pathologically
      organ-confined from locally-advanced prostate cancer in total PSA-levels below 10
      ng/ml.
AB  - BACKGROUND: We measured serum levels of human glandular kallikrein 2 (hK2) in
      patients treated with radical retropubic prostatectomy (rrP) for clinically
      localized prostate cancer (PCa) with a total PSA (tPSA)-level below 10 ng/ml to
      investigate whether hK2 can be applied to preoperatively distinguish organ
      confined (pT2a/b) from nonorgan-confined (> or = pT3a)-PCa more accurately than
      total PSA. Further, we evaluated hK2, free- and tPSA-concentrations in all
      pathologic stages of PCa. METHODS: 161 serum samples from men scheduled for rrP
      were collected 1 day before surgery prior to any prostatic manipulation.
      Pathologic work-up revealed > or = pT3a-PCa in 48 and pT2a/b-PCa in 113 patients.
      HK2-levels in serum were measured using an immunofluorometric assay with an
      analytical sensitivity of 0.5 pg/ml, a functional sensitivity of 5 pg/ml and
      insignificant cross-reactivity with PSA (< 0.005%). Total (tPSA) and free PSA
      (fPSA) levels were measured using a commercially available assay from which we
      calculated %fPSA and an algorithm that combined hK2 and PSA-levels [hK2] x
      [tPSA/fPSA]. Means, medians, and ranges were calculated for pT2a/b vs. >/= pT3a
      PCa and for all pathologic stages. Statistical significance of differences was
      calculated using Mann-Whitney-U and Kruskal-Wallis tests. Calculation of receiver
      operator-characteristic (ROC) curves were performed for hK2, [hK2] x [tPSA/fPSA]
      and tPSA to compare diagnostic performance. RESULTS: A mean tPSA level in serum
      of 6.12 ng/ml in > or = pT3a-PCa was not significantly different (P = 0.366) from
      5.78 ng/ml in pT2a/b-PCa. Also, there were no statistically significantly
      different levels of fPSA (P = 0.947) or %fPSA (0.292) for these two groups. By
      contrast, mean hK2-level in pT2a/b-PCa of 80 pg/ml was significantly different (P
      = 0.004) from a mean hK2 level of 120 pg/ml in > or = pT3a-PCa as shown by Mann
      Whitney-analysis Moreover, the algorithm of [hK2] x [tPSA/fPSA] was significantly
      lower (P = 0.0004) in pT2a/b-PCa vs. > or = pT3a-PCa. Calculation of areas under
      curve (AUC) by receiver-operator-characteristics (ROC) demonstrated that the AUC
      for hK2 (0.64) was larger and the AUC for [hK2] x [tPSA/fPSA] (=0.68)
      significantly larger (P = 0.007) compared to the AUC of tPSA (0.55). Furthermore,
      Kruskal-Wallis Test revealed a highly significant correlation to pathologic stage
      using hK2 (P = 0.008) and [hK2] x [tPSA/fPSA] (P = 0.0015) compared to no
      significant differences in serum concentration of tPSA (P = 0.296). Also at tPSA
      levels from 10-20 ng/ml, the hK2-levels in pT2a/b-PCa were close to significantly
      different (P = 0.051) from those in men with >/= pT3a-PCa, while the algorithm of
      [hK2] x [tPSA/fPSA] in that tPSA-range was significantly lower (P = 0.002) in
      pT2a/b-PCa compared to > or = pT3a0-PCa. CONCLUSIONS: Highly significant
      differences in serum concentration enable hK2 to be a powerful predictor of organ
      confined disease and pathologic stage of clinically localized prostate cancer,
      especially in the PSA-range below 10 ng/ml. As such, there are important clinical
      consequences for the application of hK2 for the adequate treatment of prostate
      cancer patients, i.e., the option of nerve-sparing surgery. (c) 2001 Wiley-Liss,
      Inc.

PMID- 11582589
TI  - Hypermethylation of the CD44 gene is associated with progression and metastasis
      of human prostate cancer.
AB  - BACKGROUND: CD44 is a metastasis suppressor gene for prostate cancer and the down
      regulation of CD44 and its variants is associated with the progression of
      prostate cancer. Also, hypermethylation of the CpG islands of the CD44 gene is
      closely associated with transcriptional inactivation, resulting in the decreased
      expression of CD44. To clarify the exact role of methylation status of CpG
      islands of CD44 gene in the progression and metastasis of prostate cancer, we
      investigated the methylation status of this gene in primary and metastatic human
      prostate tumors obtained from surgery or autopsy. METHODS: We examined 97 samples
      from 40 Japanese patients with adenocarcinoma of the prostate. Tumor tissues were
      obtained from radical prostatectomy specimens from eight patients with stage B,
      12 patients with stage C and three patients with stage D1 and at autopsy from 17
      hormone-refractory metastatic cases, who had initially responded to the therapy
      and thereafter relapsed. Distant metastatic tissues were also obtained at autopsy
      (i.e., liver, lung, kidney, mammary gland, and pelvic lymph nodes) from 10 of 17
      hormone-refractory cases. We analyzed the hypermethylation status of CD44
      promotor region by PCR using genomic DNAs digested with the m(5)C-sensitive
      restriction enzyme HpaII. RESULTS: The correlation between the methylation status
      of CD44 gene and the stage progression of prostate cancer was statistically
      significant (P = 0.0438). In two of 10 hormone-refractory cases, a comparison of
      the methylation status of the CD44 gene in metastases to that in primary tumors
      revealed interfocal heterogeneity of CD44 methylation status. CONCLUSIONS: These
      results indicate an important role of CD44 methylation in the progression and
      metastasis of prostate cancer, although the amount of methylational heterogeneity
      is substantial among metastatic sites within the same patient.

PMID- 11582590
TI  - A potential autocrine pathway for growth hormone releasing hormone (GHRH) and its
      receptor in human prostate cancer cell lines.
AB  - BACKGROUND: Recent studies have shown that GHRH antagonists inhibit prostate
      tumour growth and IGF-II production both in vivo and in vitro. The mechanism
      underlying these observations is unknown, but may involve an interaction with a
      prostatic GHRH receptor (GHRH-R), raising the possibility of an autocrine pathway
      for the GHRH axis in the prostate. METHODS: GHRH and GHRH-R mRNA expression was
      examined by RT-PCR in human prostate cancer cell lines, and the authenticity of
      PCR products was confirmed by Southern analysis and cDNA sequencing.
      Immunohistochemical techniques were used to examine the expression of GHRH
      protein in prostate cancer cell lines. RESULTS: GHRH-R (mRNA) and GHRH (mRNA and
      protein) are co-expressed in the ALVA-41, DU145, LNCaP and PC3 human prostate
      cancer cell lines. CONCLUSIONS: These observations suggest the presence of an
      intact prostatic GHRH autocrine pathway which may stimulate prostate cell
      proliferation. This pathway may be disrupted by GHRH antagonists.

PMID- 11582591
TI  - Effect of cernitin pollen-extract on experimental nonbacterial prostatitis in
      rats.
AB  - BACKGROUND: The treatment for chronic nonbacterial prostatitis (NBP) has not been
      established. Cernitin pollen-extract (CN-009) is reported to have therapeutic
      effects for NBP. The effects and mechanisms of CN-009 were investigated. METHODS:
      Ten-month-old rats were used with administration of estradiol after castration,
      which were similar to human NBP histologically. Since CN-009 consists of T-60 and
      GBX, these drugs were administered, respectively. The prostate was evaluated
      histopathologically including glandular damage (epithelial score), stromal ratio
      and immunohistochemical assays for epithelial function (PAP), stromal evaluation
      (Vimentin), cell proliferation (PCNA) and apoptosis (deoxyuridine triphosphate
      biotin nick end-labeling (TUNEL)). RESULTS: Controls revealed severe acinar gland
      atrophy and stromal proliferation. CN-009 showed diminished these damages.
      Epithelial score was better (P < 0.01) and PAP positive materials were more
      abundant in CN-009 and GBX than in Controls. The stromal ratio was lower in CN
      009 (P < 0.01) and T-60 (P < 0.05). There was no difference for PCNA positive
      cells in the epithelium and stroma, and TUNEL positive cells in epithelium.
      While, the number of TUNEL positive cells in the stroma of CN-009 and T-60
      increased (P < 0.01). CONCLUSIONS: These findings suggest that CN-009 protects
      acinar epithelial cells mainly by GBX and also inhibits stromal proliferation in
      association with enhanced apoptosis mainly by T-60.

PMID- 11582592
TI  - Proliferative activity and branching morphogenesis in the human prostate: a
      closer look at pre- and postnatal prostate growth.
AB  - BACKGROUND: To gain further insight into the molecular cell biologic features of
      prostate development, we investigated the proliferative activity of prostate
      epithelial and stromal cells and their topographic relationship with
      neuroendocrine (NE) cell distribution and regional heterogeneity. METHODS:
      Consecutive sections from 43 prostates taken during autopsy representing fetuses
      (12-38 weeks of gestation), infants, prepubertal males and adults were double
      stained for chromogranin A and MIB-1. MIB-1 labeling index (LI) was calculated in
      the budding tips, forming acini, major collecting ducts, adjacent and non
      adjacent stromal compartments. Furthermore, the topographic relationship between
      proliferating cells and NE cells was evaluated. RESULTS: In the first half of
      gestation, cell proliferation as revealed by MIB-1 LI was significantly higher in
      epithelial structures and stroma than in older fetuses and other age groups. MIB
      1 LI was higher in budding tips than in other epithelial regions. MIB-1 LI in
      stroma adjacent to budding tips was not higher than that adjacent to other
      epithelial branching segments. Co-expression of chromogranin A and MIB-1 staining
      was not observed. MIB-1 LI was lower in cells in the direct vicinity of
      chromogranin A positive NE cells than at a distance from NE cells. CONCLUSIONS:
      Prostate development in the first half of gestation is explosive. Thereafter, the
      prostate basically is a slow-growing organ. Budding tips are the major growth
      foci during early prostate development, while stromal growth is evenly
      distributed throughout the prostate, probably indicating that stromal-epithelial
      interactions do not manifest in enhanced proliferation at their interface. NE
      cells may have an inhibitory effect on proliferation of exocrine epithelial cells
      and are probably only associated with differentiation of prostate exocrine cells
      in the prostate.

PMID- 11582593
TI  - Molecular staging of surgical margins after radical prostatectomy by detection of
      telomerase activity.
AB  - BACKGROUND: The further course of prostate cancer (PC) after radical
      prostatectomy (RPX) is decisively influenced by the local tumor stage. Although
      it is thus far possible to assess the risk of local recurrence from the
      pathohistology, precise predictions cannot be made. A more precise evaluation
      would be desirable, mainly for early planning of adjuvant therapy. Other authors
      have shown that telomerase activity may be a marker for malignant potential. We
      assessed the detection of telomerase activity using the telomeric repeat
      amplification protocol (TRAP) in surgical margins compared to conventional
      histopathological examination. METHODS: Ninety-two patients with local PC who
      underwent RPX were examined. After RPX biopsies were obtained from four defined
      areas of the prostatic fossa and processed by TRAP assay for telomerase activity
      using a standard protocol. RESULTS: In 5 of 48 patients (10.4%) with organ
      confined prostate carcinoma (pT2) telomerase activity could be detected. Seven of
      47 patients (14.9%) with locally advanced PC (> pT2) had at least one positive
      specimen. CONCLUSIONS: The results obtained in our study indicate that detection
      of telomerase activity by TRAP assay may be a suitable parameter for molecular
      staging of surgical margins, because of the high tumor-specificity. Further
      follow-up must clarify whether patients with positive molecular detection have an
      increased risk of local recurrence.

PMID- 11582594
TI  - Melatonin elicits nuclear exclusion of the human androgen receptor and attenuates
      its activity.
AB  - BACKGROUND: The androgen receptor (AR) promotes growth and functionality of
      androgen sensitive benign and cancer tissues. The pineal hormone melatonin is an
      androgen protagonist in vivo and in vitro. The interference of melatonin in the
      AR cascade was explored. METHODS: The effects of melatonin on AR expression,
      level, agonist and androgen-response element (ARE) binding, reporter gene
      activity and intracellular localization were explored in prostate cancer LNCaP
      cell line. RESULTS: Melatonin increased immunoreactive AR cells in the absence
      and presence of dihydrotestosterone. Despite this increase and maintenance of AR
      agonist binding capacity, the androgen-induced reporter gene activity and
      suppression of AR-mRNA were attenuated. Immunocytochemical analysis and
      subcellular fractionation studies revealed nuclear exclusion of AR by melatonin.
      CONCLUSIONS: The melatonin-mediated nuclear exclusion of the AR may explain the
      attenuation of AR activity in the prostate cancer cells. This is the first
      demonstration of a hormone-induced mislocalization of the AR in prostate
      epithelial cells and may represent a novel route for regulating AR activity.

PMID- 11582595
TI  - Publications from extracurricular research.

PMID- 11582596
TI  - Hospital documentation requirements.

PMID- 11582597
TI  - Ask the doctor. I'm a 42-year-old man with no health problems, except for the
      fact that I'm a bit overweight. I recently had an exercise test because of some
      chest pain. The good news is that it showed no evidence of heart problems, but
      during the test my blood pressure quickly shop up to 190 mm Hg. Usually, it's
      about 35/90 mm Hg. The doctor doing the test didn't seem too alarmed, but I'm
      concerned.

PMID- 11582598
TI  - Ask the doctor. I read that Vice President Cheney received an implantable
      defibrillator because of some extra beats on his electrocardiogram. I've also had
      some extra beats, but I've never had a heart attack or any other heart problems.
      My doctor told me not to worry. Is the Vice President getting better care than I
      am?

PMID- 11582599
TI  - Epidemiology in the 21st century. The challenges ahead.

PMID- 11582600
TI  - Surveillance of HIV infection and related risk behaviour in European prisons. A
      multicentre pilot study.
AB  - BACKGROUND: In order to demonstrate the feasibility of human immunodeficiency
      virus (HIV) infection and related risk behaviour surveillance in European
      prisons, a multicentre pilot study was undertaken. METHODS: A cross-sectional
      survey was carried out in six European prisons (France, Germany, Italy, The
      Netherlands, Scotland and Sweden). Inmates were invited to complete a self
      administered and anonymous questionnaire and to give a saliva sample in order to
      test for HIV antibodies. RESULTS: Eight hundred and forty-seven out of 1,124
      inmates participated in the survey (response rate 75%). Saliva from 817 inmates
      (73%) was collected and processed for HIV antibodies. Twenty-seven per cent
      reported that they had ever injected drugs and 49% of these reported they had
      injected whilst in prison. Eighteen per cent of inmates reported that they had
      been tattooed whilst in prison, which was found to be higher among injecting drug
      users (IDUs). One and sixteen per cent reported that they had ever had homosexual
      and heterosexual intercourse in prison respectively. The HIV prevalence among
      IDUs was 4% (versus 1% among non-IDUs) (p = 0.02). The proportions of inmates
      previously tested for hepatitis C and vaccinated against hepatitis B were 24 and
      16% respectively. CONCLUSION: This survey demonstrates the feasibility of cross
      sectional surveys in European prison inmates and highlights the importance of
      surveillance of HIV prevalence and related risk behaviour among inmates. The
      continuing high HIV prevalence and potential for HIV spread in prisons should
      encourage decision makers in implementing or enhancing harm reduction and
      education programmes and substance abuse treatment services in prison.

PMID- 11582601
TI  - Highly active antiretroviral therapy (HAART). Awareness and beliefs about
      infectivity and the influence on sexual behaviour in the general population of
      Sweden.
AB  - The purpose of the present study was to assess the relationship between the
      awareness of HAART, beliefs regarding transmission of HIV of persons taking
      HAART, norms associated with sexual risk behaviour, fear of HIV/AIDS, optimism of
      finding a cure or vaccine, and sexual behaviour in the general population of
      Sweden. A mail survey was sent to 4,000 randomly selected individuals aged 16-44
      years. The study shows that the general public of Sweden is aware of HAART. Only
      15% of the population had never heard of HAART. Eight percent believed that those
      taking HAART were 'no longer' or 'less' infective. Those not aware of HAART
      reported greater fear of HIV infected persons, less volunteer testing for HIV,
      and more sexual partners. Those who believed that persons taking HAART were less
      infective reported greater fear, more optimism concerning the possibilities to
      find a cure or vaccine, and had more discussions regarding HIV. We conclude that
      a group that may be at increased risk of HIV infection may be persons who are not
      aware of HAART or believe that persons are no longer infective when taking HAART.
      These persons may be an additional target group for HIV prevention.

PMID- 11582602
TI  - AIDS and contraception. Unanticipated effects of AIDS prevention campaigns.
AB  - BACKGROUND: This study addresses the effects of AIDS prevention campaigns on
      contraceptive practices among the general population in France. Comparisons of
      contraceptive practices and condom use by women aged 18-49 years were performed
      in two national population-based surveys (n = 559 in 1994, n = 731 in 1998).
      RESULTS: A decrease in the proportion of women aged 20-24 with multiple partners
      reporting the use of contraception was observed between 1994 and 1998. In the
      same time, there was an increase in the use of condoms to prevent AIDS.
      CONCLUSION: Findings suggest that single-risk prevention campaigns on AIDS may
      lead some women to pay less attention to the risk of unwanted pregnancy.

PMID- 11582603
TI  - Telephone prescribing of antibiotics. General practitioners' views and
      reflections.
AB  - BACKGROUND: In this era of increasing problems with resistance, rational
      prescribing of antibiotics is extremely important. Therefore, rationales for
      prescribing require analyses. The objective of this study was to explore general
      practitioners' (GPs') reasons for prescribing antibiotics by telephone. METHODS:
      Qualitative analysis of semistructured interviews with and observations of GPs in
      Iceland enquiring about the rationale for prescribing antibiotics was used. Ten
      GPs were interviewed for 45 min to 2 h each including three who were observed
      between 3 and 10 h. RESULTS: The GPs generally indicated a restrictive attitude
      to telephone prescribing, although they all gave examples of their prescribing by
      telephone. The prescribing was mostly but not always based on some kind of
      diagnosis. The factors influencing diagnosis and prescribing were largely non
      clinical: knowledge of the patients as persons, including their complaint
      threshold, confidence in their descriptions, the GPs' communication strategies
      and the travelling distance between patients and GPs. The clinical factors were
      the patients' description of signs and symptoms and knowledge of their history.
      Prescriptions not based on diagnosis were 'therapeutic trial' or GP-approved self
      medication. Sometimes, the GPs requested to see a patient even though the
      diagnosis was based on history, signs and symptoms. CONCLUSIONS: Multiple factors
      affected the decision-making process when antibiotics were prescribed by
      telephone, most of which were non-clinical. The diagnosis, if there was one, was
      generally presumptive. GPs' general attitudes correlated well with current
      knowledge but were contrasted by the reality of their daily work conditions.

PMID- 11582604
TI  - GP income in relation to workload in deprived urban areas in The Netherlands.
      Before and after the 1996 pay review.
AB  - BACKGROUND: General practitioner workload is higher in deprived urban areas and
      for the elderly. This led to the introduction of additional GP payments regarding
      these patients, in the UK and in the Netherlands. This study examines whether
      this has resulted in more equal payment for work done in the Netherlands.
      METHODS: GP workload and income have been assessed on the basis of a survey among
      1154 GPs (response: 62%). RESULTS: Suggest that total GP income is still lower in
      deprived areas, but per hour and per patient contact the additional payments gave
      equity. CONCLUSION: It is thus concluded that Dutch deprivation payments
      effectively compensate GPs in deprived areas for their higher workload.

PMID- 11582605
TI  - Emotional and physical demands on caregivers in home care to the elderly in
      Switzerland and their relationship to nursing home admission.
AB  - BACKGROUND: Planning the home care of growing numbers of old, dependent people
      must include the caregivers' burden. METHODS: A convenience sample of 129
      caregivers of elderly patients with multiple diagnoses was interviewed about the
      caregiving context, burden, caregivers' tolerance of patients' troublesome
      behaviours and physical symptoms, mutuality and feelings of closeness between
      caregiver and patient. Continued maintenance of home care was assessed by a
      follow-up telephone call. RESULTS: Caregivers were mainly spouses (67%) and
      female (73%), and the mean duration of care was 5.5 years. In five activities of
      daily living (ADL) 50-69% of the patients needed full help. Caregivers reported
      predominantly negative effects of caregiving on their physical and mental health,
      rest and sleep, leisure time and social life, problems with patients' symptoms
      and behaviours and little or no conversing (51%) or exchanging feelings with
      patients (71%). PREDICTIVE MODELS: Contributors to variance were for burden
      (35%), impact of care on caregivers' mental health, social relations and leisure
      time, patients' gender, accumulation of patients' symptoms and behaviours; for
      caregivers' tolerance toward patients' symptoms and behaviours (17%) caregivers'
      physical health, patients' level of confusion, feelings of mutuality; for
      mutuality (22%) and for closeness (19%) caregivers' mental health, patients'
      accumulation of symptoms and behaviours. Within 23 months 19% of the patients had
      been institutionalized. Factors giving a higher likelihood of
      institutionalization were: being male, caregiver was not a partner, and less
      closeness between caregiver and patient. CONCLUSION: Caregiving of older persons
      has bio-psychosocial ramifications for caregivers. Closeness between caregiver
      and patient seems to be a key factor in determination of the long-term outcome.

PMID- 11582606
TI  - Health beliefs and illness attitudes as predictors of breast cancer screening
      attendance.
AB  - BACKGROUND: This paper considers the breast cancer screening programme in the
      autonomous community of Navarre, Northern Spain. Women from different areas of
      Northern, Central and Southern Navarre are involved. METHODS: A sample of 512
      women participants and 196 non-participants was taken from a total of 60,908
      women between 45 and 65 years of age who received an invitation to attend the
      breast cancer screening programme. The participants were asked to fill in an
      individual structured questionnaire in their local Health Centre and the non
      participants in their homes. This was done retrospectively. RESULTS: The response
      rate was 100% for participants and 83.9% for non-participants. This study
      investigates the attitude profiles of the women attending mammography mass
      screening, with non-attending women (matched in educational and occupational
      levels) as controls. Subjects were assessed on dimensions such as attitudes
      towards health and illness. The results support Rosenstock's 1974 model that
      perceived severity of breast cancer and perceived susceptibility to breast cancer
      are related to participation in screening. Furthermore, results demonstrated that
      hypochondriacal beliefs, disease phobia and feared effects of symptoms were
      related to decreased participation levels. CONCLUSION: This study has explored
      the implication of health belief attitudes and the attitudes toward illness
      variables with women's participation in a breast cancer screening programme. It
      assesses the relative contribution of these variables to levels of participation,
      and the results of the study indicate that belief sets and attitudes are
      important components of women's cancer prevention behaviours.

PMID- 11582607
TI  - Socioeconomic differences in use of medical care and antibiotics among
      schoolchildren in Sweden.
AB  - BACKGROUND: Studies of mortality among children and adults in Sweden have
      demonstrated considerable socioeconomic differences. This paper describes
      socioeconomic patterns of physical morbidity and use of medical care and
      antibiotics in schoolchildren in Sweden. METHODS: A cross-sectional study based
      on parent interviews from the Swedish Survey of Living Conditions in 1996-1997
      was used. The study population consisted of 3,557 children aged 6-15 years.
      RESULTS: Forty-five percent of the schoolchildren in the study were reported to
      have been absent from school because of illness at least once during the previous
      three months, 8% were taking regular medication and 10% had ever suffered from a
      chronic disorder. There were no indications of socioeconomic differences
      according to the education of the responding parent in morbidity or use of
      consultations with a physician. However, children in families where the
      responding parents had primary education only consumed antibiotics less often (OR
      0.7 and CI: 0.5-0.9) when compared to children in families with post-secondary
      education. Children in rural areas used consultations with a physician less often
      and consumed less antibiotics (adjusted OR 0.7 and CI: 0.4-0.9 and 0.7 and CI:
      0.5-0.9 respectively). CONCLUSION: No obvious patterns of socioeconomic
      inequality in physical morbidity or use of medical care were identified among
      schoolchildren in Sweden. Further studies are needed in order to explain the
      social inequality in consumption of antibiotics among schoolchildren in Sweden
      and to describe social and regional patterns of psychiatric, behavioural and
      psychosomatic morbidity.

PMID- 11582608
TI  - Mortality of young adults in relation to single-parent family background. A
      prospective study of the northern Finland 1966 birth cohort.
AB  - BACKGROUND: The relationship between family background and mortality of offspring
      was studied by using a prospectively collected, general population, birth cohort
      database (n = 11,017), that is the Northern Finland 1966 birth cohort which is
      linked with the national death register. METHODS: A logistic regression analysis
      was performed in order to examine the association between family background and
      death of offspring (between ages 16 and 28 years). RESULTS: It was revealed that
      117 subjects (90 males and 27 females) from the original birth cohort had died.
      The majority of the deaths were due to unnatural causes in both sexes (79%).
      After adjusting for confounders (psychiatric diagnosis and parental social
      class), the results indicated that the general mortality risk for males with a
      single-parent family background was significantly increased compared with males
      from a two-parent family background (odds ratio 1.8 and 95% confidence interval:
      1.1-2.9). The risk of committing suicide was significantly increased among young
      adult males with a single-parent family background (OR 2.5 and 95% CI: 1.1-5.8).
      CONCLUSION: Our finding calls for health care professionals to provide more
      preventative mental health support for children and adolescents living in broken
      homes.

PMID- 11582609
TI  - Social equalization in the health of youth. The role of the school.
AB  - BACKGROUND: A study was made of the role of the school in the process of social
      equalization in the health of pre-adolescents and adolescents in the city of
      Bern, Switzerland. METHODS: Questionnaire data obtained from 578 13-year-olds and
      476 15-year-olds within the frame of the evaluation of a health-promoting schools
      project were transformed to 30 indicators of well-being at school, health,
      emotional well-being, life-skills, and health behaviour and attitudes. RESULTS:
      Multiple logistic regression with gender, social class, ethnicity, and school
      climate as independent variables revealed the disappearance of social gradients
      by 15 years of age and the emergence of new inequalities related mainly to gender
      and school climate. CONCLUSIONS: The school contributes to the social
      equalization of the health of adolescents but creates at the same time new
      disparities, with probably long-lasting consequences. The factors determining the
      school climate have to be studied more in depth.

PMID- 11582610
TI  - Patterns of unhealthy behaviour in Finland.
AB  - BACKGROUND: The aim of the study was to examine associations between unhealthy
      behaviours among the Finnish adult population. METHODS: Data from a series of
      cross-sectional health behaviour surveys from the years 1991-1998 were pooled.
      Associations between smoking, alcohol consumption, lack of regular physical
      activity and unhealthy diet were examined among 22,745 respondents. The
      associations were first studied in terms of accumulation: the occurrence of each
      combination of unhealthy behaviours was compared to their expected appearance,
      assuming that the behaviours were independent from each other. The same
      associations were then analysed with log-linear models. RESULTS: Only 2.4% of men
      and 0.9% of women had all four unhealthy behaviours. Nevertheless, the occurrence
      of four unhealthy behaviours was about three times more common than expected
      under the assumption of independence of the behaviours. Also, most of the three
      behaviour combinations showed accumulation. Among the pairwise combinations,
      smoking and alcohol consumption as well as physical inactivity and unhealthy diet
      showed strongest accumulation, whereas the combination of alcohol consumption and
      unhealthy diet was less prevalent than expected. The combination of four healthy
      behaviours appeared 1.3 times more often than expected. In log-linear analysis a
      model containing all pairwise associations and the three-behaviour interaction
      between smoking, alcohol consumption and physical inactivity, as well as that of
      alcohol consumption, physical inactivity and unhealthy diet for men, provided an
      acceptable fit. Most of the unhealthy behaviours were positively associated but
      the association between alcohol consumption and unhealthy diet was inverse. Other
      behaviours modified the strength of the associations. The direction of the
      association between alcohol consumption and physical inactivity depended on other
      behaviours. CONCLUSIONS: Unhealthy behaviours showed pairwise and multiple
      accumulation. No three-behaviour associations were reducible to pairwise
      associations. Smoking had the strongest and most consistent associations with
      other unhealthy behaviours. Differences between sociodemographic groups were
      small and the patterns of unhealthy behaviour were remarkably similar among men
      and women.

PMID- 11582611
TI  - The impact of structural factors on the injury rate in different European
      countries.
AB  - BACKGROUND: A previous study pointed to there being two kinds of injuries--those
      with a mainly social genesis and those with a mainly environmental genesis. The
      aim of this study was to analyse how socioeconomic factors--such as level of
      economic development, alcohol consumption and unemployment and more cultural
      factors--such as education and religion--relate to kinds of injury. METHODS:
      Motor vehicle traffic accidents were chosen to represent injuries with a
      predominantly environmental genesis and suicides those with a mainly social
      genesis. Qualitative comparative analysis (QCA) complemented by Pearson
      correlation was employed. The data come from 12 European countries. RESULTS: Four
      groups of countries emerged from the analysis. Group 1 was high on both kinds of
      injuries and was also high on all the independent variables considered. Group 2
      was low on social injuries and high on environmental injuries; it had a low level
      of economic development, high alcohol consumption and a high proportion of Roman
      Catholics. Group 3 was high on social injuries and low on environmental injuries;
      it had a high level of economic development, low alcohol consumption and few
      Roman Catholics. Group 4 was low on both kinds of injuries; the independent
      variables formed a similar pattern to those of group 3. CONCLUSION: The pattern
      for traffic fatalities differs from that of suicides. There is also patterning
      with regard to structural factors; economic level, education and religion seem to
      be more important with regard to injury rate differentials than alcohol
      consumption or unemployment.

PMID- 11582612
TI  - Injury risks and socioeconomic groups in different settings. Differences in
      morbidity between men and between women at working ages.
AB  - BACKGROUND: It is unclear whether greater injury risk in lower socioeconomic
      groups at working ages is attributable to differences in work conditions or a
      reflection of a wider overall pattern of risk. The current study investigates
      socioeconomic differences in non-fatal injury risks in a variety of settings.
      METHODS: Data were taken from a community-based injury register built up over one
      year (November 1989 to October 1990) in a semi-urban Swedish municipality
      (256,510 inhabitants), and then linked by record to Sweden's National Population
      Register (based on the census of 1990). Injuries among the age group 20-64 were
      considered. Age-standardized odds ratios were computed by gender for five injury
      settings and four socioeconomic groups, using salaried employees as the reference
      group. RESULTS: Compared with salaried employees, male manual workers and from
      the unspecified population (long-term unemployed, students, etc.) show an excess
      risk of injury in all settings except sports. Males from all socioeconomic groups
      show significantly higher morbidity in production/education areas. Female manual
      workers show significantly higher morbidity in home settings and in
      production/education; those from the unspecified population, in home settings,
      transport areas, and 'other areas'. CONCLUSION: Higher morbidity in lower
      socioeconomic groups results not only from work-related differences, where 25% of
      the injuries analysed were incurred, but also from the differential impacts of
      other living environments, e.g. home and transport areas. Differences between
      socioeconomic groups in care seeking, injury lethality, injury susceptibility,
      and risk exposure may influence the social patterning of injury morbidity.

PMID- 11582613
TI  - Russian-American partners for prevention. Adaptation of a school-based parent
      child programme for alcohol use prevention.
AB  - BACKGROUND: The Russian-American Partners for Prevention was an adaptation and
      evaluation of the Slick Tracy Home Team Program which was developed in Minnesota
      in order to delay the onset of drinking. The Slick Tracy Home Team Program was
      the first intervention of Project Northland, a large 3 year community trial of
      the efficacy of a public health intervention for under age drinking. METHODS: The
      programme was administered through schools, but involved parents using engaging
      and fun homework activities. The Russian version was implemented in fifth-grade
      classrooms in 20 Moscow schools with 1,212 students surveyed at baseline.
      Students were surveyed again after programme implementation (n = 1,182), of whom
      980 were present at baseline. Parents of 1,078 students were surveyed by
      telephone after programme implementation. RESULTS: The results demonstrated the
      successful recruitment and retention of 20 Moscow schools in a research project,
      acceptability of programme materials in Russia, high participation rates, changes
      in students' knowledge about problems associated with under age drinking and some
      evidence about increases in parent-child communication about alcohol use. As in
      the USA, no changes in students' alcohol use rates were observed at the end of
      the first year of the 3 year programme. CONCLUSION: Russian youth, as compared to
      Americans, began drinking at earlier ages, received fewer prevention messages
      from their parents, and had fewer prevention programmes in school. The results
      suggested that carefully implemented and evaluated replications of the US Project
      Northland interventions might provide effective and appropriate school-based
      programmes for Russia.

PMID- 11582614
TI  - Adolescent use of anabolic-androgenic steroids and relations to self-reports of
      social, personality and health aspects.
AB  - BACKGROUND: Over the last decade adolescent males have been shown to use anabolic
      androgenic steroids (AAS) in order to improve their sports performance and
      appearance, as well as in combination with alcohol and psychotropic drugs.
      However, the risk profile of AAS use is still not well understood. This study
      analysed the importance of social, personality and health factors for the use of
      AAS. METHODS: More than 2,700 senior high school students in Uppsala, Sweden,
      filled out an anonymous closed-response questionnaire. RESULTS: The findings from
      multiple logistic regression analyses of adolescent males (n = 1,353) showed that
      immigrant status, average/low self-esteem, average/low perceived school
      achievement and use of prescription tranquillisers/sedatives had independent
      significant associations with the use of AAS after controlling for age and
      previously known factors such as strength training, truancy and heavy alcohol
      consumption. CONCLUSION: The characteristics of AAS users extend beyond
      activities such as strength training and multiple drug use to include social,
      personality and health aspects.

PMID- 11582615
TI  - The impact of maternal smoking during pregnancy on delivery outcome.
AB  - BACKGROUND: Maternal smoking during pregnancy is associated with pre-term birth,
      intrauterine growth retardation, a small head circumference, a low Apgar score at
      5 min and stillbirths and neonatal deaths. This study was undertaken in order to
      investigate the impact of maternal smoking during pregnancy when all these
      outcomes were considered. METHODS: With the use of the Swedish Medical Birth
      Registry, infants in any one of the above mentioned outcome groups were selected
      from 1,413,811 infants born between 1983 and 1996 with known smoking exposure in
      early pregnancy. Confounders such as year of birth, maternal age, parity and
      educational level were controlled for. The attributable risk of maternal smoking
      on the various negative delivery outcomes was obtained by application of the risk
      estimates to population counts. RESULTS: The present study confirmed the
      associations between maternal smoking and the miscellaneous outcomes mentioned
      above with high significance. The odds ratios (with 95% confidence intervals) for
      maternal smoking (< 10 cigarettes/day and > or = 10 cigarettes/day) for any one
      of the outcomes were 1.39 (1.37-1.41) and 1.65 (1.62-1.68) respectively (dose
      response p < 0.001). The number of attributable cases caused by maternal smoking
      was estimated at 15,000, which represents 9% of all cases and 1% of all infants
      born in Sweden during the study period. CONCLUSION: Maternal smoking during
      pregnancy accounts for a substantial part of various negative delivery outcomes.

PMID- 11582616
TI  - Postpartum return to smoking among usual smokers who quit during pregnancy.
AB  - BACKGROUND: Many women stop smoking while they are pregnant, but the majority
      resume smoking in the postpartum. The objective is to describe postpartum tobacco
      use of women who quit during pregnancy and factors predicting postpartum smoking
      relapse. METHODS: Secondary analysis of two surveys of new mothers. Survey A
      conducted in three maternity hospitals, including 685 women interviewed after
      birth and who answered a postal questionnaire at 5 months postpartum; survey B
      conducted in four 'departements' (administrative areas), including 636 women who
      answered a postal questionnaire at 6 months postpartum. Response rates were
      respectively 90% and 68%. Smoking status was recorded for three time periods:
      before pregnancy, during pregnancy, and at 5-6 months. Social characteristics and
      preventive behaviour were compared for regular smokers who had quit smoking
      during pregnancy and those who had not, and among quitters, who had resumed
      smoking postpartum and those who had not. RESULTS: In survey A, 37% were smokers
      before pregnancy, 34% of them stopped during pregnancy, and among the latter, 48%
      had resumed smoking 5-6 months after delivery. In survey B, the percentages were
      respectively 43, 54 and 57%. The most predictive factor of postpartum smoking
      relapse was the partner's smoking behaviour. CONCLUSION: Return to smoking after
      delivery is frequent, but nearly half of the regular smokers who had stopped
      during pregnancy were still non-smokers 5-6 months after the birth. However, to
      increase this proportion, interventions need to include partners, especially if
      they are smokers.

PMID- 11582617
TI  - Between harm and dangers. Oral snuff use, cigarette smoking and problem
      behaviours in a survey of Swedish male adolescents.
AB  - BACKGROUND: The prevalence of smokeless tobacco use (moist snuff) in Sweden is
      among the highest world-wide, and snuff is gaining popularity as a less harmful
      alternative to cigarettes. METHODS: Patterns of current tobacco use and
      indicators of behavioural problems were analysed in a sample of 6287 boys
      participating in a census survey among 9th graders in Stockholm County, Sweden.
      RESULTS: Among participants reporting current use of oral snuff (OS) the majority
      (71%) also smoked cigarettes. The prevalence of daily smoking was significantly
      higher in this group than among exclusive smokers. Conditionally on smoking
      behaviour, the likelihood of being a current user of OS was several times higher
      among boys who had ever been drunk (adjusted odds ratio = 9.64, 95% confidence
      interval: 7.32-12.94) or experimented with illicit drugs (adjusted odds ratio =
      2.39, 95% confidence interval: 1.99-2.87), compared with those who did not. OS
      use was also significantly associated to other problem behaviours such as
      drinking and driving, unsafe sex, and school truancy. The same pattern of
      associations was present when the analyses were restricted to tobacco users.
      CONCLUSIONS: Smokeless tobacco use in adolescence does not substitute cigarette
      smoking and can be an indicator of a drug- and risk-seeking lifestyle. The
      availability of smokeless tobacco might thus increase the potential for nicotine
      addiction in some vulnerable subgroups of young males.

PMID- 11582618
TI  - Profile of the population of Spain with respect to the smoking habit, period 1993
      1997.
AB  - The consumption of tobacco has become by far the main avoidable cause of disease
      and premature death in Spain. There is a trend towards picking up the tobacco
      habit at an earlier age for both males and females. The number of women smokers
      is rising, particularly in the younger age groups (45% of women between the ages
      of 16 and 22 claim to be smokers) almost equalling male levels, which are
      remaining constant. The objective of this study is to profile current smokers,
      former smokers and never smokers among Spanish men and women, based on subject
      characteristics, and compare the profiles estimated for 1993, 1995 and 1997. We
      use a two-level nested logistic regression model to model the adoption and
      cessation processes of the smoking habit. The first level or branch discriminates
      between persons who have never been smokers and people who have been smokers or
      who are smokers at present. The second level is to discriminate between present
      smokers and former smokers (succeeded in the cessation process). The results show
      that the variables which define the profile of smokers include so-called stress
      related factors, if the individual is separated or divorced, whether she is
      unemployed. The cessation process accelerates with age and is stimulated by the
      diagnosis of chronic disease, particularly heart disease. Our results, which are
      fairly stable from 1993 to 1997, should provide guidelines in the development of
      prevention and control of tobacco consumption health policies.

PMID- 11582619
TI  - Can the declining prevalence of left-handedness with age be due to smoking?
AB  - The objective of this study was to assess whether smoking habits can explain the
      decline in left-handedness prevalence with age. Subjects participating in a
      population-based survey (n = 3,071) in Geneva, Switzerland, completed a
      questionnaire on innate hand preference, current hand preference for writing and
      smoking habits. The prevalence of innate left-handedness in the Geneva population
      was 9.4% in men and 7.4% in women. There was no association between smoking and
      left-handedness. It is concluded that smoking is not associated with hand
      preference and is an unlikely cause of overmortality in left-handed subjects.

PMID- 11582620
TI  - Historic low Haemophilus influenzae type B case tally--Canada 2000.

PMID- 11582621
TI  - Outbreak of Salmonella enteritidis phage type 913 gastroenteritis associated with
      mung bean sprouts--Edmonton, 2001.

PMID- 11582622
TI  - Management of acute myocardial infarction in Portugal. Results of a nationwide
      survey.
AB  - The management of acute myocardial infarction (AMI) has improved markedly over
      the last decade. Large-scale trials have produced a large amount of evidence, and
      recommendations and guidelines have been established. Whether and to what extent
      these data have influenced everyday practice on a nationwide scale remains to be
      ascertained. The present observational prospective, registry was designed to
      assess current practice in in-hospital management of AMI in Portugal. For a
      period of 3 months (February to May, 1999), 44 centers, distributed all over the
      country, Atlantic islands included, enrolled 1372 cases of AMI corresponding to
      1366 patients (996 male, mean age 65 +/- 13 years; 370 female, mean age 72 + 11
      years; p < 0.0001). Non-ST segment elevation infarcts were present in 26% of
      cases. In-hospital mortality was 11.2% (154 pts, mean age 74 +/- 10 years).
      RESULTS: 519 pts (37.8%) were managed with reperfusion therapy, 413 of them with
      fibrinolysis (30.1%) and 106 with primary PTCA (7.7%). Besides the invasive
      procedures performed within the first few hours after admission, coronary
      angiography was performed in 327 more pts (26.1%); 143 pts were revascularized
      (PTCA in 117 pts and CABG in 26) and 96 more pts were discharged and referred for
      further revascularization. The total number of pts given or referred for a
      revascularization procedure (including the primary treatment) was 316 (20.6%).
      Besides reperfusion therapy the most commonly used drugs for secondary prevention
      were aspirin in 91%; ACE inhibitors in 63%; beta-blockers in 45%; and statins in
      28%. Based on the results of this nationwide survey it can be concluded that the
      main international guidelines and recommendations for the medical management of
      acute myocardial infarction are generally being applied in Portugal.

PMID- 11582623
TI  - The first steps have been taken. Now we need to continue.

PMID- 11582624
TI  - Atrial flutter ablation with a new radiofrequency catheter.
AB  - OBJECTIVE: To assess the performance of a new radiofrequency catheter, specially
      designed for inferior vena cava-tricuspid annulus (IVC-TA) isthmus ablation, in
      the treatment of atrial flutter. PATIENTS: IVC-TA isthmus ablation was performed
      in thirteen patients, eleven men and two women, aged 60 +/- 12, with a diagnosis
      of typical atrial flutter, symptomatic despite anti-arrhythmic therapy. The
      flutter was present for more than one year in seven patients and was paroxysmal
      in the remainder. The echocardiogram showed atrial enlargement in six patients.
      Atrial flutter was an isolated phenomenon in seven patients and in the remainder
      was associated with arterial hypertension (two patients), ischemic heart disease
      (two patients) and dilated cardiomyopathy (two patients). METHODS: In the
      electrophysiologic study four diagnostic catheters were used, including one
      duodecapolar for mapping the tricuspid annulus. In the patients who presented
      with sinus rhythm, atrial flutter was induced with programmed atrial stimulation,
      and then the atrial activation circuit was mapped. To demonstrate the entrainment
      phenomenon the IVC-TA isthmus was over-stimulated, to prove that this was the
      slow zone of the circuit. The radiofrequency energy was applied in the IVC-TA
      isthmus with the Medtronic Cosio-Fluttr ablation catheter, for 60 sec per
      application, with temperature control and with a maximum energy output of 50 W.
      Criteria for success were not only the disappearance of the atrial flutter during
      the application of radiofrequency energy, but also the demonstration of bi
      directional IVC-TA isthmus block. RESULTS: The primary success rate was 100%. The
      mean procedure time was 110 +/- 22 min, mean fluoroscopy time was 23 +/- 4 min
      and the number of radiofrequency energy pulses was 9 +/- 3. There were no
      complications. The patients were followed for a mean time of 8 +/- 4 months and
      atrial flutter recurred in only one patient (8%). CONCLUSIONS: Atrial flutter
      ablation with the new Medtronic Cosio-Fluttr catheter, specially designed for the
      application of radiofrequency at the IVC-TA isthmus, is a safe procedure and has
      a high success rate. It simplifies ablation, decreasing the number of
      radiofrequency energy pulses, without using long sheaths and keeping short
      procedure and fluoroscopy times.

PMID- 11582625
TI  - Percutaneous occlusion of patent foramen ovale in patients with paradoxical
      embolism.
AB  - INTRODUCTION: A patent foramen ovale can be found in about one quarter of adults
      and in a small percentage it is a wide opening and may be associated with
      aneurysmal formation. The association between a wide patent foramen ovale and
      paradoxical embolism is well established. In such cases percutaneous closure is
      indicated, as an alternative to life-long anticoagulant therapy or surgery.
      Percutaneous closure is an attractive technique and is more advantageous than
      other methods. METHODOLOGY: We describe the first cases of percutaneous occlusion
      of patent foramen ovale performed in Portugal, using the Amplatzer PFO occluder,
      in three female patients with documented cerebrovascular accidents due to
      paradoxical embolism. We also analyze the rationale for using this technique in
      such patients and its preliminary results. RESULTS: All three patients submitted
      to percutaneous occlusion of patent foramen ovale had a similar history of
      ischemic cerebrovascular accident. Transesophageal echocardiography showed a wide
      open foramen ovale ranging from 9 to 12 mm, with spontaneous right-to-left shunt
      in all patients, and one of them also had an aneurysmal formation. Total
      procedure time ranged from 30 to 55 minutes and fluoroscopic time from 9 to 12
      minutes. There were no complications and during the short follow up all patients
      are asymptomatic and free of recurrent events. CONCLUSIONS: Percutaneous closure
      of patent foramen ovale is a safe and promising technique in the prevention of
      recurrent systemic thromboembolism in appropriately selected patients.
      Prospective studies comparing antithrombotic therapy or surgery with percutaneous
      closure should clarify its efficacy and therapeutic value.

PMID- 11582626
TI  - [Cardiac effects of acute poisoning with tricyclic antidepressants: systematic
      review of the literature -- Part II].
AB  - Tricyclic antidepressant overdose is a frequent diagnosis in the emergency room.
      It is responsible for a significant percentage of hospital admissions for
      observation and treatment. This is due to its cardiac (as well as neurologic)
      toxicity, and the difficulty in predicting its clinical gravity. The authors
      present this paper with two objectives in mind: 1) information about a common and
      significant cardiological emergency; 2) presentation of the methodology
      concerning systematic reviews of the literature. In this second (of four)
      articles, the clinical presentation and diagnosis of tricyclic antidepressant
      overdose are presented (in the first article--published in the previous issue of
      the Journal--we discussed the epidemiological aspects). In the remaining two
      papers we will present its management, prognosis and prevention. NOTE: This is
      the second of a series of four articles on the cardiac toxicity of tricyclic
      antidepressant overdose; the next two articles will be presented in the September
      and October issues of the Revista.

PMID- 11582627
TI  - [Congenital cardiopathy in adults. Part II -- Cyanotic cardiopathy].

PMID- 11582628
TI  - Cardiac troponin I in systemic diseases. A possible role for myocardial strain.
AB  - Cardiac troponin I levels are frequently above normal values in several disease
      states in which myocardial necrosis is not a prominent aspect, particularly in
      pulmonary embolism, heart failure, liver cirrhosis, septic shock, renal failure
      and arterial hypertension. Sub-clinical myocardial necrosis has been postulated
      to be the cause of the phenomenon. Studies performed so far have not included
      pathological data to confirm this hypothesis. Increased troponin I plasma levels
      may be the result of myocardial strain, especially the type of strain that
      accompanies some forms of cardiac dilatation or hypertrophy. Troponin I may act
      as a marker of myocardial strain, either acute (in pulmonary embolism, septic
      shock and acute heart failure) or chronic (in chronic cardiac, renal and hepatic
      failure, as well as in arterial hypertension). The apparent paradox of elevated
      levels of troponin I without elevated levels of creatine kinase in several
      disease states might be solved if troponin I could be released from myocardial
      cells without the disruption of myocardial cell plasma membranes. Precise
      pathological studies are needed to elucidate whether increased troponin I with
      normal CK is associated with myocyte death, and, if so, with necrosis or with
      apoptosis.

PMID- 11582630
TI  - [Fifty years of Framingham Study contributions to understanding hypertension].

PMID- 11582629
TI  - A "ring-shaped" image at the mitral valve with complications arising from
      endocarditis.

PMID- 11582631
TI  - Early diagnosis of silent coronary artery disease in diabetic subjects--are
      intense efforts worth while?

PMID- 11582632
TI  - Silent coronary artery disease in patients with diabetes mellitus.
AB  - Coronary artery disease (CAD) represents the leading cause of death in diabetic
      patients. Silent myocardial ischaemia more often occurs in diabetics than in non
      diabetics. It has been well recognised that silent myocardial ischaemia is not
      different from symptomatic ischaemia with respect to prognosis and adverse
      events. Asymptomatic high-risk diabetic patients therefore might benefit from
      routine screening for silent ischaemia and risk stratification; furthermore,
      silent ischaemia has to be treated accordingly.

PMID- 11582633
TI  - Antiretroviral prophylaxis for community exposure to the human immunodeficiency
      virus in Switzerland, 1997-2000.
AB  - OBJECTIVE: To analyse the data from Swiss nationwide voluntary reporting on non
      occupational HIV-postexposure prophylaxis (HIV-PEP) by prescribing physicians.
      METHODS: One hundred and seventy-six persons, who received antiretroviral
      prophylaxis for community exposure to HIV between December 1997 and March 2000,
      were included in this prospective cohort study with standardised data collection.
      Information on the source, the exposed person, type of exposure, treatment, and
      outcome was reported by physicians on a voluntary basis to three co-ordinating
      centers. RESULTS: HIV-PEP was prescribed predominantly following sexual exposure
      (69%). Needle injury was the second most common type of exposure (19% of all
      exposures), mostly occurring in a non-healthcare related "professional" setting
      (i.e., housekeepers, concierges [caretakers], and policemen). Needle sharing
      accounted for only 4% of all cases of exposure. The HIV status of the source
      often remained unknown (56%). Most patients received a combination of three
      antiretroviral drugs (zidovudine/lamivudine/nelfinavir in 34.1%;
      zidovudine/lamivudine/indinavir in 22.8%; zidovudine/lamivudine/nevirapine in
      18.6%; various triple combinations in 13.8%). Follow-up information was available
      for 86 patients. In this group 78 (91%) completed at least one week of
      prophylaxis. Side-effects were common (70.9%), particularly diarrhoea (29.6%) and
      nausea (20.9%). Two patients experienced severe side effects, nephrolithiasis
      with sepsis, and toxic hepatitis, respectively. CONCLUSIONS: In most of the cases
      where HIV-PEP was prescribed the indication was questionable, with the HIV status
      of the source unknown. The role of HIV-PEP as part of HIV prevention programs
      should be well defined in view of the cost and potential for causing severe side
      effects.

PMID- 11582634
TI  - Use of broad spectrum antibiotics in six non-university Swiss hospitals.
AB  - PRINCIPLES: Broad-spectrum antibiotics (BSAs) are costly and prone to misuse.
      Their use is associated with the emergence of resistant bacteria. This article
      describes the first step of an interhospital programme for the appropriate use of
      BSAs. METHODS: BSAs were defined as the i.v. antibiotics present in the formulary
      shared by the six participating institutions and considered to be antipseudomonal
      agents (i.e. cefepime, ceftazidime, ciprofloxacin, imipenem, meropenem,
      piperacillin/tazobactam) plus trovafloxacin. Annual utilisation rates and
      interhospital comparisons were provided to each institution using the "defined
      daily dosages" (DDDs) of the World Health Organization. RESULTS: From 1997 to
      1999, the overall utilisation rate of BSAs increased from 20.6 treatment days
      (TD)/1000 patient days (PD) to 36.5 TD/1000 PD. Significant interhospital
      differences were detected (range: 12.1 TD/1000 PD in 1997-66.5 TD/1000 PD in
      1999). The highest relative risk for treatment with any BSA for each individual
      hospital in comparison to the others was determined for 1999 (RR = 2.92; 95%
      confidence interval: 2.81-3.04). In 1999, the most frequently used BSAs were
      cefepime, imipenem, and piperacillin/tazobactam respectively. CONCLUSIONS:
      Although this programme does not provide information on the indications for using
      BSAs in various hospitals, it helps to identify those institutions where the
      selection pressure for resistant bacteria is highest, and that could particularly
      benefit from specific interventions aiming at decreasing this pressure and
      controlling drug expenditure. Moreover, the feedback of utilisation rates and
      interhospital comparisons to the prescribing physicians might have a positive
      impact on BSA use.

PMID- 11582635
TI  - Helicobacter pylori infection and complicated peptic ulcer.

PMID- 11582636
TI  - Surgical treatment for pathologic fracture.
AB  - AIM: To evaluate epidemiology, prognosis and diagnostics in metastatic bone
      disease and identify risk factors for failure after operation for pathologic
      fracture. PATIENTS: The study was based on patients treated for skeletal
      metastases, myeloma or lymphoma between 1986 and 1998 at the Oncology Service,
      Department of Orthopedics, Karolinska Hospital and on patients diagnosed with
      symptomatic skeletal metastases 1989-1994 in the Stockholm Region. EPIDEMIOLOGY:
      641 breast cancer patients were diagnosed with symptomatic skeletal metastases
      1989-1994. Based upon 1100 new primary breast cancer cases yearly, the overall
      risk of developing symptomatic skeletal metastases was 10-15%. One out of 5
      patients with skeletal metastases required surgical treatment for skeletal
      complications. PROGNOSIS: The survival rate after surgical treatment for skeletal
      complications was 0.3 at 1 year and 0.008 at 3 years. Multivariate analysis based
      on 619 patients showed that complete pathologic fracture and soft tissue
      metastases were negative prognostic variables for 1-year survival after
      operation. Solitary skeletal metastasis, breast, prostate, kidney cancer,
      myeloma, and lymphoma were positive variables. DIAGNOSIS: Fine Needle Aspiration
      Biopsy (FNAB) was assessed in 110 patients for diagnostic accuracy and to which
      extent information about primary site of the metastatic carcinoma could be
      gained. There were 80 patients with metastatic carcinoma, 14 with lymphoma, and
      16 with myeloma. FNAB offered correct diagnosis in 9 of 10 patients and also
      provided guidance in the search for the primary lesions. Hence, 27 of 30 myeloma
      or lymphomas were diagnosed by FNAB and in half of the patients with metastatic
      carcinoma the site of the primary tumor could be ascertained. For patients with a
      suspected skeletal metastasis the search for the primary tumor may preferably
      start with FNAB. SURGICAL TREATMENT: Risk factors for failure after operation for
      pathologic fractures were identified in 192 patients treated for 228 metastatic
      lesions of the long bones. 26 out of 228 procedures (11%) lead to failures
      necessitating reoperation. Long survival after surgery was the most important
      risk factor for failure of the reconstruction. Kidney cancer was the primary
      tumor associated with the highest rate of reoperations. Reoperations were more
      common in the femur than in the humerus. Reconstructions based on prosthetic as
      opposed to osteosynthetic devices appeared safer. There was a tendency for a high
      reoperation rate in hospitals with few treated patients. CONCLUSION: To decrease
      the risk of reoperation, it is important to identify patients with a long
      expected survival. Patients with a good prognosis should be considered for wide
      resection and reconstruction as applied in primary malignant bone tumors.

PMID- 11582637
TI  - [Short-term steroid therapy, sometimes with long-term sequelae].
AB  - Two patients developed osteonecrosis, respectively one and two years after the
      short-term intravenous use of dexamethasone. A 35-year-old man received 150 mg
      over a period of 3 weeks associated with a craniotomy for a subarachnoidal
      haemorrhage. He developed bilateral osteonecrosis of the femoral and humeral
      heads, which necessitated bilateral hip replacement surgery. He still experiences
      pain in both shoulders. A 45-year-old woman received 42.5 mg over a period of 1
      week as a treatment for reflex dystrophy with oedema. She developed bilateral
      osteonecrosis in the femoral condyles, the talus and the calcaneus and after
      treatment she continued to experience pain in her right knee and ankle whilst
      walking. The only other risk factor for osteonecrosis identified in these
      patients was hyperlipidaemia in the man. Corticosteroid-induced osteonecrosis is
      typically multifocal and usually occurs 0.5 to 3 years after the therapy was
      initiated. There is a relationship with the dose and length of therapy. Even the
      short-term use of corticosteroids for 3 weeks or less, may lead to this
      dehabilitating complication.

PMID- 11582638
TI  - ['Evidence-based' perioperative antibiotic prophylaxis policy in Belgian
      hospitals after a change in the reimbursement system].
AB  - The costs of antibiotics in Belgian hospitals are nearly fully reimbursed by the
      health insurance. Such a situation is not conductive to rational drug use. A new
      reimbursement system for perioperatively-administered antibiotics in Belgian
      hospitals was implemented in May 1997 by Royal Decree. A reimbursement code for
      antibiotic use was linked to the reimbursement of surgical interventions. This
      code represents a reimbursement which covers 75% of the cost of perioperative
      prophylaxis based on optimal indication, dose, and duration as recommended by
      international and Belgian consensus guidelines. The actual antibiotic prescribed
      during the 72-hour perioperative period (the day before, during and after
      surgery) is reimbursed at only 25% of its full cost. Thus, if the perioperative
      prophylactic antibiotic regimen complies with the evidence-based guidelines, the
      costs of antibiotic prescribing will be fully reimbursed by the health insurance
      (75% of the standard +25% of the actual costs). The new reimbursement system does
      not apply to antibiotics which are prescribed for treatment of intercurrent
      infections; these antibiotics continue to be fully reimbursed. Annual
      expenditures for antibiotics, for both antibiotic treatment and prophylaxis,
      nationwide and per hospital, have shown marked improvements in perioperative
      antibiotic use after the decree was implemented. Surgeons' adherence to the
      evidence-based standard of prophylactic antibiotic use has improved over time. In
      conclusion, rapid implementation of the perioperative antibiotic prophylaxis
      policy was achieved through changes in the reimbursement of antibiotics for
      surgery patients.

PMID- 11582639
TI  - [Rosacea in the year 2001].
AB  - Rosacea is a chronic skin disorder of the face. Initially erythema and
      telangiectasia develop, followed at a later stage by papules and papulopustules.
      Females between 30 and 50 years of age are most affected. Pathogenesis is not
      clearly understood. Finally rhinophyma and persistent lymphoedema can develop. It
      can be difficult to distinguish acne vulgaris, seborrheic eczema, perioral
      dermatitis and lupus erythematosus from rosacea. Treatment of first choice
      consists of topically or systemically applied antibiotics. More severe cases can
      be treated with isotretinoin. Erythema and telangiectasia respond well to
      treatment with vascular lasers.

PMID- 11582640
TI  - [Fractional and coronary flow reserve: intracoronary diagnosis of coronary artery
      disease]].
AB  - A decision to perform coronary angioplasty on a constricted coronary artery
      should always be preceded by objective evidence of myocardial ischaemia in the
      flow region concerned. However, for patients with multi-vessel coronary disease
      it can be difficult to determine which of the several coronary stenoses present
      is responsible for the anginal complaints. Recently, special miniaturized sensor
      equipped guide wires are introduced in the cardiac catheterisation laboratory.
      Therefore it is now possible to selectively evaluate coronary stenoses by means
      of haemodynamic parameters: fractional flow reserve (FFR, based on intracoronary
      derived pressure measurements) and coronary flow velocity reserve (CFVR, based on
      intracoronary derived Doppler flow velocity measurements). The diagnosis of
      coronary artery disease in the cardiac catheterisation laboratory has improved
      considerably due to the use of these intracoronary derived haemodynamic
      parameters. Several clinical studies have shown that it is safe to defer a
      coronary angioplasty based on an FFR > or = 0.75 or a CFVR > or = 2.0. In the
      case of an abnormal FFR or CFVR result, the appropriate treatment strategy can be
      implemented. Furthermore, these parameters can be used to evaluate the result of
      the therapy.

PMID- 11582641
TI  - [Diagnostic image (55). Thalamus hemorrhage with intraventricular invasion].
AB  - A 54-year-old man presented with headache and cognitive deterioration without
      other neurological signs, caused by intraventricular, thalamic, and caudate
      nucleus haemorrhage. He had longstanding hypertension, a known risk factor.

PMID- 11582643
TI  - [One year of neonatal screening for sickle-cell disease in Emma Children's
      Hospital/Academic Medical Center in Amsterdam].
AB  - OBJECTIVE: Early detection of children with sickle cell disease, determination of
      carriership frequency as well as evaluation of the knowledge regarding this
      haemoglobinopathy in various ethnic risk groups. DESIGN: Prospective. METHODS:
      From 1 November 1998 through to 31 October 1999, the ethnic background was
      recorded for consecutive pregnant women under care of the Academic Medical
      Centre, Amsterdam, the Netherlands, and the presence of carriership for sickle
      cell disease was evaluated. Carriers were asked about their knowledge of sickle
      cell disease. A diagnostic blood test of cord blood was also performed using a
      PCR which could detect both haemoglobin S and C mutations. RESULTS: Fifty-five
      carriers were detected in a group of 1,016 investigated pregnant women (5.4%).
      The carriership frequencies in Surinam and African women were 12 and 15.7%,
      respectively. Knowledge of sickle cell disease, its occurrence in populations at
      risk, as well as the terms 'inheritance' and 'carriership', differed
      substantially between Surinam and African women, with awareness being lower in
      the latter group. In six cases informed consent was not asked. All other 49
      carriers consented to a diagnostic test. Two intrauterine deaths occurred. Four
      children had sickle cell disease: three had HbSS, one had HbSC. Nineteen children
      proved to be carriers for sickle cell disease, 18 were heterozygotes for HbS, one
      for HbC. CONCLUSION: This targeted neonatal screening for sickle cell disease was
      feasible in a hospital setting. The number of children diagnosed with the disease
      supports the wider implementation of this method of early detection.

PMID- 11582644
TI  - [Tumor of the omentum in 2 patients with a large, mobile mass in the upper
      abdomen].
AB  - A mobile mass in the right upper abdomen was felt in an 81-year-old woman with
      nausea and a 45-year-old man with exertional dyspnoea. Radiological
      investigations did not reveal sufficient information, whereupon laparotomies were
      carried out. In both cases, a tumour was found at the exit of the greater
      omentum. Following resection, the tumour recurred in the woman five months later,
      and she died as a result; the man made a rapid recovery and remained tumour-free
      two years later. Tumours originating in the omentum majus are rare. The
      presentation of these tumours is late, due to late presentation of complaints.
      These tumours are usually only detected once they reach a diameter of more than
      10 centimetres. In general, it is difficult to establish whether the tumour is
      benign or malignant either pre- or peri-operatively. Surgery is the only curative
      option. A wide resection is preferable, with resection of any (parts of) organs
      which may be involved.

PMID- 11582645
TI  - [New research on the practice, reporting and reviewing of euthanasia and other
      medical end-of-life decisions, 2001/2002].
AB  - In the second half of 2001, an extensive study will start which will evaluate the
      review procedure for euthanasia in the Netherlands. Since the end of 1998,
      euthanasia has to be reviewed by regional review committees, which include a
      physician and an ethicist, in addition to a legal expert. The aim of this study
      is to examine whether the reporting procedure meets the aim and whether there are
      any points which require improvement. This study follows on from those carried
      out in 1990/1991 and 1995/1996, which investigated euthanasia and other medical
      end-of-life decisions (assisted suicide, termination of life without the
      patient's explicit request, treatment of pain and symptoms with a possible life
      shortening effect, and forgoing potentially life-prolonging treatment). The study
      consists of an analysis of cases of death (in which the numbers and nature of
      various medical end-of-life decisions will be established), physician interviews
      (to gain insight into the context in which medical end-of-life decisions are
      made), a study of reported cases (to give an overview of doctors' experiences
      with the review committees), and a study carried out amongst the general public
      (around 1,500 Dutch adults will be given a written questionnaire about their
      opinions concerning medical end-of-life decisions and the reporting procedure).
      In addition to this Dutch study, a European study subsidized by the European
      Commission is being carried out which will examine attitudes and experiences
      regarding medical end-of-life decisions in six European countries (Belgium,
      Denmark, Italy, the Netherlands, Sweden and Switzerland). This will, for the
      first time, enable a true comparison to be made between the Netherlands and other
      countries in terms of euthanasia and other medical end-of-life decisions.

PMID- 11582646
TI  - [Death certification in the Netherlands: inadequate procedures for unnatural
      death, found corpses and deaths of persons with unknown identity].
AB  - The Dutch burial act regulates procedures regarding death certificates. Various
      subjects, such as the term 'unnatural death', found bodies and dead persons with
      unknown identity, are insufficiently regulated in this (and other) laws.

PMID- 11582647
TI  - [Unclear roles of district medical examiner and the attending physician in cases
      of natural and unnatural deaths in the Netherlands].
AB  - The role of the attending physician and the district medical examiner in the case
      of a natural or unnatural death is subject to a number of legal regulations. The
      different parts of a postmortem examination, the conditions for the issue of a
      death certificate, the term 'attending physician', and the position and duties of
      the district medical examiner are not, however, unequivocally specified in Dutch
      law. This gives rise to frequent misunderstandings.

PMID- 11582648
TI  - [Roaming through methodology. XXXIV. Limitations of predictive models].

PMID- 11582649
TI  - [An eye on the vocal cords; family practitioners and hoarseness].

PMID- 11582650
TI  - [Diagnostic image (48)].

PMID- 11582651
TI  - [Psychiatric illness does not protect against a somatic disease].

PMID- 11582652
TI  - Intellectual property and the human genome (Part I).

PMID- 11582653
TI  - [The new frontier of the right to privacy].
AB  - From the right to privacy there derives a right to genetic privacy to protect
      individuals from some of the potential threats that may arise with respect to
      advances in Biology. Here we look at the basis for the proposed concept of the
      right to genetic privacy and examine issues concerning the legal nature, the
      active and passive subjects, the limitations and guarantees of this right.

PMID- 11582655
TI  - [Conclusions of the decision of the Constitutional Division of the Supreme Court
      of Justice of Costa Rica on the prohibition against in vitro fertilization].

PMID- 11582654
TI  - Ethics and law, a compass to guide us on a new map: the human genome.

PMID- 11582656
TI  - [In the absence of a bioethics debate. Comments on the Decision of the
      Constitutional Division of the Supreme Court of Justice of Costa Rica on the
      prohibition against in vitro fertilization].
AB  - The ruling by Costa Rica's Constitutional Court on the prohibition of in vitro
      fertilisation is a consequence of the negligible development of Bioethics, the
      lack of public debate on the issue and the absence of adequate regulation.
      Prohibition of such a vital medical technique represents an abuse of power by the
      courts, and thus curtails other fundamental rights, research, progress and
      bioethics' debate.

PMID- 11582657
TI  - The moral status of animals in the discussions on xenotransplantation (Part II).

PMID- 11582658
TI  - The ethics of genetics in Russia.

PMID- 11582659
TI  - [Human dignity as a key notion in the UNESCO declaration on the human genome].
AB  - The notion of human dignity plays an increasing role in the bioethical
      discussion. The UNESCO Universal Declaration on the Human Genome and Human Rights
      is the best example of this phenomenon. This instrument is the first important
      step to establish international standards with regard to the ethical and legal
      problems raised by genetic advances. Nevertheless, the major work is still
      pending. First, because the concept of dignity requires a better characterization
      with reference to the new bioethical dilemmas. Second, because the principles
      enunciated at the international level should be concretized locally through well
      crafted national law.

PMID- 11582661
TI  - [Towards a supranational integration of the guiding principles on the human
      genome. A personal view from the Latin American perspective].
AB  - All human groupings draw up a range of values and valuational ideals. Man alone
      draws up values and it is these that confer content on cultures. In this
      particular subject matter one might speak of guiding principles regarding the
      Human Genome. These guiding principles are ethical values, recognised as such by
      the vast majority of humankind in the Western Christian culture of our time.

PMID- 11582660
TI  - [Draft bill for the regulation of DNA bases].
AB  - With regard to the possible setting up in our country of a DNA data base for
      criminal identification purposes, the author undertakes a series of reflections-
      with constant reference to Comparative Law--on the draft Bill governing DNA data
      bases and underlines the timeliness and positive contribution of this legislative
      initiative. However, he also draws attention to several aspects of the proposed
      legislation which are clearly in need of improvement.

PMID- 11582662
TI  - [Nuclear ploidy of mammary glandular and ductal epithelial cells in diagnosis of
      carcinogenesis stages].

PMID- 11582663
TI  - [Endogenic intoxication markers: data from capillary electrophoresis of
      trichloroacetic acid supernatant].
AB  - Capillary electrophoresis is suggested for characterization of trichloroacetic
      acid (TCA) supernatant in various visceral diseases involving endogenous
      intoxication. The technique of electrophoresis is described. Examples of
      electrophoregrams are offered with extrapolation to common clinical laboratory
      values. The appearance of a positive "cationic peak" instead of a negative
      systemic peak observed in health is a specific electrophoretic sign of endogenous
      intoxication. The area of the peak (proportionate to intoxication) and its ratio
      to the group undivided peak observed in the distal part of electrophoregram
      (minutes 8-14, anionic constituents) are significant. The values of the latter
      peak characterize the defense characteristics of the organism and are in
      proportion to them. Capillary electrophoresis is a perspective diagnostic method.

PMID- 11582664
TI  - [Novel methods in diabetes mellitus diagnosis].
AB  - Analysis of the lacrimal fluid was carried out for the diagnosis of diabetes
      mellitus in 68 patients. Collection of tears is absolutely painless, atraumatic,
      and involves virtually no risk of viral infections. Analysis of the lacrimal
      fluid is particularly valuable for repeated analyses over the course of disease.
      A method for postmortem diagnosis of diabetes mellitus and hyperglycemic coma by
      measuring glucose in the vitreous body is suggested. The content of glucose in
      the vitreous higher than 17 mmol/liter is a specific marker indicating death from
      hyperglycemic coma.

PMID- 11582665
TI  - [Diagnostic significance of detection of medium weight molecules in infectious
      endocarditis].

PMID- 11582666
TI  - [Magnesium and calcium ion levels in peritoneal fluid of healthy fertile women].
AB  - The purpose of this study was to establish normal values of Ca2+ and Mg2+ ions in
      the peritoneal fluid (PF) of fertile women. PF was aspirated during laparoscopy
      in 19 women subjected for surgical sterilization for social reasons. The
      concentrations of Ca2+ and Mg2+ in PF were normal. In fertile women the
      peritoneal concentrations of these ions do not depend on serum concentrations.
      Normal range of Ca2+ concentration in PF is 0.9-1.28 mmol/liter, that of Mg2+ 0.4
      0.57 mmol/liter. In genital diseases the concentrations of Mg2+ are changed in
      78.8% cases and those of Ca2+ in 45.8% cases.

PMID- 11582667
TI  - [Lipid peroxidation and antioxidant system parameters in lacrimal fluid in post
      traumatic uveitis].
AB  - Lipid peroxidation (LPO) values and activities of antioxidant enzymes, catalase,
      and superoxide dismutase were studied in the lacrimal fluid (LF) of the damaged
      and intact eyes of 87 patients with posttraumatic uveitis (PTU). Catalase
      activity was decreased in sluggish PTU and increased in exacerbation, which is
      attributed to decompensation of the antioxidant system and its effect on the
      course of posttraumatic inflammation. Similar changes were detected in LF of
      paired eyes. Long treatment with antioxidants is recommended; the authors
      consider that analysis of the paired eye LF cannot be used for control in
      patients with PTU.

PMID- 11582668
TI  - [Etiologic structure of acute purulent meningitis and methods of microbiological
      diagnosis].

PMID- 11582669
TI  - [Clinical significance of NADPH-dependent dehydrogenases in lymphocytes from
      patients with bronchial asthma].
AB  - The activities of lymphocyte NADP-dependent dehydrogenases were evaluated in 84
      children with atopic asthma during relapses and clinical remission. The pattern
      and severity of changes in the studied enzymes depended on children's age and
      duration and severity of disease. Changes in the older age group and during
      relapse were the deepest and most stubborn. During remission the activities of
      the studied oxidoreductases did not reach the parameters observed in healthy
      children. Changes in the activities of NADP-dependent dehydrogenases in blood
      lymphocytes objectively reflect the course of allergic inflammation in patients
      with atopic asthma and can be clinically used for evaluation of the pathological
      process at a metabolic level.

PMID- 11582670
TI  - [Quantitative determination of proteins and mucin (glycoproteins) in saliva].

PMID- 11582671
TI  - [Fat embolism diagnosis].

PMID- 11582672
TI  - [Correction of the lipid composition of the liver plasma membranes during
      heliotrine intoxication].
AB  - Antioxidant properties of yantocine, a preparation derived from Alhagi
      pseudalhagi Desy, were studied on a model of acute toxic hepatitis induced in
      random bred young male albino rats (90-100 g). Two experimental models were used:
      acute geliotrine hepatitis and acute CCl4 hepatitis. Yantocine was added to
      preparations of damaged plasma membranes (PM) in ascending doses. The results
      indicate that the level of malonic dialdehyde in the rat liver PM depended on the
      drug dose in both models of hepatitis. Linear dependence was observed for doses
      of 1.0-5.0 gamma. The capacity of yantocine to decrease the production of lipid
      peroxided was confirmed in vivo. After 3-day treatment with yantocine the level
      of lipid peroxides decreased by 15 and 12%, respectively, while the content of
      total phospholipids increased negligibly.

PMID- 11582673
TI  - [Standardization of immunophenotyping of human blood and bone marrow cells. Part
      I. Preanalytical phase. Part II. Indirect immunofluorescence].

PMID- 11582674
TI  - [Cytokine production in patients with chronic viral hepatitis C during treatment
      with interferon-alpha].
AB  - Serum content of proinflammatory cytokines (IL-1 beta, IL-6, TNF-alpha) and
      growth factors (GM-CSF, TGF-1 beta) and expression of CD14 and CD95 antigens on
      peripheral blood monocytes before and after 12-day therapy with alpha-interferon
      were studied in 25 patients with chronic viral hepatitis C (VHC). The
      concentrations of TNF alpha, GM-CSF, and TGF-1 beta were significantly increased
      (p < 0.05) and coexpression of CD14+ and CD95+ antigens on monocytes was
      increased by 61% in VHC patients in comparison with the control. After 3 months
      of therapy with alpha-interferon, the content of TNF alpha, GM-CSF, and TGF-1
      beta essentially decreased and that of IL-6 increased; this was paralleled by
      improvement of clinical and laboratory parameters and decrease of coexpression of
      CD14+ and CD95+ antigens on blood monocytes. Modulation of the functions of
      immunocompetent cells and changed production of cytokines are apparently one of
      the mechanisms of inhibitory effect of alpha-interferon on HCV infection. Study
      of proinflammatory cytokines and growth factors in the serum and expression of
      CD14 and CD 95 antigens on monocytes can serve as additional tests for evaluating
      the efficiency of interferon therapy in patients with VHC.

PMID- 11582675
TI  - [Macroglobulin-IgG complex concentration as a criterion for prognosis of gestosis
      and assessment of its severity].

PMID- 11582676
TI  - [On the article by Morozova M G et al "High performance liquid chromatography of
      corticosteroids in patients with depression and depersonalization" (Klin Lab
      Diagn 2000;(4):14-6)].

PMID- 11582678
TI  - ["General quality control" principles and experience of their application at the
      Medical center of the Central bank of the Russian Federation].

PMID- 11582677
TI  - [Diagnostic significance of evaluating erythrocyte membrane permeability as an
      intoxication syndrome criterion].
AB  - Twenty-five patients with pyoinflammatory maxillofacial diseases treated in an
      inpatient setting in the Regional Dentistry Clinic of Krasnodar and 8 healthy
      volunteers were examined. After opening and draining of the purulent focus the
      patients were divided into 2 groups. Group 1 consisted of 21 patients treated by
      intravenous 0.04% sodium hypochlorite (SHC) and intravenous infusions of SHC
      oxidized autoblood for 2-3 days. Group 2 (6 pts) was treated by intravenous
      infusions of SHC-oxidized autoblood for 6 days. The criteria of intoxication were
      erythrocyte resistance tests in hypotonic sodium chloride and at different
      concentrations of urea in isotonic medium. A new method for evaluating
      erythrogram deviations from reference values is proposed, which helps adequately
      assess the severity of intoxication.

PMID- 11582679
TI  - [Disseminated intravessel blood coagulation in blood vessel trauma].

PMID- 11582680
TI  - What customers want. Research shows how the safety footwear industry's buying
      habits are changing.

PMID- 11582682
TI  - Protecting the hand-skin barrier in the workplace.

PMID- 11582681
TI  - Renewing your hand protection program.

PMID- 11582683
TI  - A monumental achievement.

PMID- 11582684
TI  - Differential diagnosis of occupational hearing loss.

PMID- 11582685
TI  - No more guesswork. At last, hearing protectors can be fit tested!

PMID- 11582686
TI  - Preventing WMSDs.

PMID- 11582687
TI  - Concentrating on comfort.

PMID- 11582688
TI  - Four steps to an effective office ergonomics program.

PMID- 11582689
TI  - A safety program's best friend.

PMID- 11582690
TI  - Dipping into the labor pool.

PMID- 11582691
TI  - Why safety committees fall short.

PMID- 11582692
TI  - Universal appeal.

PMID- 11582693
TI  - An eye on the bottom line.

PMID- 11582694
TI  - Advantages of risk-based project management.

PMID- 11582695
TI  - Taking control of chemical management.

PMID- 11582696
TI  - Portable privacy? Here's the lowdown on HIPAA--its status and how it affects you.

PMID- 11582697
TI  - New solutions for MSDS management.

PMID- 11582698
TI  - Saving cash with compliance.

PMID- 11582699
TI  - The language of LOTO.

PMID- 11582700
TI  - What you should know.... ...about on-site saliva drug and alcohol testing.

PMID- 11582701
TI  - A cure for boredom.

PMID- 11582702
TI  - Retail falls: the whole story.

PMID- 11582703
TI  - Safety pays ... but it sure is hard to sell.

PMID- 11582704
TI  - Power plant best practices.

PMID- 11582705
TI  - Inadequate protections.

PMID- 11582706
TI  - VPP from a participant's perspective.

PMID- 11582707
TI  - Gloomy forecasts prove true.

PMID- 11582708
TI  - How we motivate.

PMID- 11582709
TI  - OSHA 300 wizard.

PMID- 11582710
TI  - Triple R dilemma. Case study: operating and maintaining HVAC systems during
      renovation.

PMID- 11582711
TI  - Intel's hand injury success story.

PMID- 11582712
TI  - Fifty years of hand protection. Gloves in the work place: past, present, and
      future.

PMID- 11582713
TI  - [Clinical applications of methods for assessing the autonomic nervous system].
AB  - This paper will review the usefulness of the evaluation of the autonomic control
      in cardiovascular and non-cardiovascular diseases, such as heart failure,
      hypertension, myocardial infarction and diabetes. Emphasis will be given to the
      relevance of the parasympathetic/sympathetic alterations found in the above
      mentioned conditions in determining the cardiovascular risk profile of the
      individual patient.

PMID- 11582714
TI  - [Autonomic nervous system adaptation during physical exercise].
AB  - Physical exercise is a physiologic condition in which a variety of mechanisms and
      production/control systems combine and interact in order to accomplish the
      desired task (physical exercise) and preserve and/or restore body homeostasis.
      The autonomic nervous system provides a double response during exercise: at first
      a prevailing parasympathetic withdrawal followed, with the increase in duration
      and intensity of exercise, by a prevailing sympathetic activation. These
      modifications interact with the regulation of breathing, of body temperature, and
      of oxygen transport from the lungs to the body tissues through the modulation of
      the cardiac pump function and of the systemic and local vasoactivity and, at a
      tissue level, through the modulation of the local metabolism and the production
      of vasoactive and chemoactive substances. In the present review these aspects and
      the effects of physical training on the autonomic nervous system are examined in
      normal subjects and in patients with heart failure.

PMID- 11582715
TI  - [Physiopathology of the autonomic nervous system activity during sleep].
AB  - Sleep consists of two phases that periodically alternate: the rapid eye movement
      (REM) phase and the non-REM phase. The non-REM stage is characterized by wide
      synchronous waves in the electroencephalogram, by a low heart rate and by a
      decrease in arterial blood pressure and peripheral resistances. This hemodynamic
      setting is the consequence of the autonomic balance characterized by high vagal
      activity and low sympathetic activity. Such an autonomic condition is adequately
      described by the spectral analysis of heart rate variability documenting a
      prevalence in the high frequency band (the respiratory vagal band). The REM stage
      of sleep is characterized by asynchronous waves in the electroencephalogram and
      it is associated with a further increase in the vagal dominance of the autonomic
      balance resulting in a lower heart rate and decreased peripheral resistances. The
      REM phase of sleep is, however, also characterized by hemodynamic instability due
      to sudden bursts of sympathetic activity, associated with the rapid eye
      movements. These sympathetic bursts cause sudden changes in heart rate and
      peripheral resistance and may influence cardiac electrical stability both at the
      atrial and ventricular levels. Additionally, REM sleep may enhance the risk of
      anginal attacks in coronary artery disease patients. Analysis of the autonomic
      balance during the different phases of sleep may also help in the identification
      of autonomic derangements typically associated with myocardial infarction.

PMID- 11582716
TI  - [Altitude and the autonomic nervous system].
AB  - Ascent to high altitudes arouses the sympathetic nervous system in non
      acclimatized healthy humans. Such activation is provoked by hypobaric hypoxia
      combined with other stressors. While this is an adaptive response, it also
      contributes to the general physical deterioration consequent to prolonged
      exposure to high altitudes, and is even implied in specific syndromes: acute
      mountain sickness, high altitude pulmonary edema (HAPE), and high altitude
      cerebral edema. Muscular sympathetic nervous activity increases at simulated high
      altitudes (hypoxic mixture or hypobaric chamber), and HAPE-susceptible subjects
      show an exaggerated response. Increases in plasma and urinary catecholamines take
      several days to appear: they are observed rarely at simulated altitudes but
      frequently on the field. Heart rate variability decreases at high altitudes,
      particularly in subjects suffering from acute mountain sickness. The low
      frequency component has been described in healthy subjects as increased or
      decreased, but is reduced in sympatomatic subjects; increases in the low
      frequency/high frequency ratio are reported in all studies. Few and discordant
      data are available regarding baroreflex sensitivity at high altitudes. Some (past
      and present) authors regard parasympathetic fitness as a defense against illness
      at high altitudes. Current guidelines advise against high altitude exposure for
      cardiac patients in whom sympathetic arousal would be too risky.

PMID- 11582717
TI  - [Autonomic nervous system in arterial hypertension].
AB  - In several experimental animal models of hypertension, alterations in the
      autonomic cardiovascular drive have been shown to participate in the development
      and/or in the maintenance of high blood pressure. This has been shown to be true
      also in case of hypertension occurring in humans in whom a reduction in the
      parasympathetic influences to the heart is paralleled by an increase in the
      cardiac and vascular adrenergic tone. Several factors have been claimed to favor
      the hyperadrenergic state of essential hypertension. These include 1) a
      dysfunction in the central mechanisms physiologically inhibiting adrenergic
      outflow, 2) a sympathoexcitation induced by humoral factors (hyperinsulinemia,
      activation of the renin-angiotensin system, etc.), and 3) a functional alteration
      in arterial baroreceptors and in cardiopulmonary receptors which restrains in
      normal conditions adrenergic activity. Evidence has been provided indicating that
      the autonomic derangement occurring in hypertension contributes to the
      development of the target organ damage associated with the hypertensive state.
      This represents the rationale for employing, in the treatment of high blood
      pressure states, drugs exerting sympathoinhibitory effects.

PMID- 11582718
TI  - [Autonomic nervous system in diabetes].
AB  - Hyperglycemia and hyperinsulinemia have a primary role in determining the early
      functional and later anatomic changes at the level of the autonomic pathways
      controlling the circulation, and besides in directly influencing cardiac and
      vascular cellular targets and feed-back baroreceptor system sensitivity to
      neurohumoral modulation in patients with diabetes mellitus. The basic mechanisms
      of dysfunction and damage, and the clinical and prognostic value of diabetic
      cardiovascular dysautonomia are discussed together with the diagnostic apparatus
      and the possible therapeutic approaches.

PMID- 11582719
TI  - [The autonomic nervous system in myocardial infarction].
AB  - The occurrence of alterations in the autonomic control of cardiovascular function
      has long been known. Nevertheless, only in the last 15 years with the development
      and utilization of techniques such as heart rate variability and baroreflex
      analysis, unforeseeable amounts of information have been collected. The appraisal
      of alterations in the autonomic control mechanisms in the acute and post-acute
      phase of myocardial infarction has not only confirmed the presence of an
      increased sympathetic and of a reduced vagal modulation in most of post
      myocardial infarction patients. It has also allowed the clinically relevant
      identification of those patients with an increased arrhythmic and total cardiac
      mortality. Most the high-risk patients are indeed characterized by a marked
      reduction in heart rate variability that can be detected using different
      methodologies. For example, with time-domain analysis of heart rate variability,
      it has been shown that an SDNN < 70 ms identifies patients at risk. By using
      spectral analysis, it has been possible to realize that the loss or marked
      attenuation of those rhythmical components that reflect autonomic modulation is
      also a characteristic of the high-risk patients. A decreased responsiveness of
      the sinus node to autonomic inputs may also explain the reduction in baroreflex
      sensitivity that characterizes patients with an increased arrhythmic mortality.
      In conclusion, the appraisal in each patient of the extent of the alterations in
      the autonomic control mechanism is nowadays a critical component of the clinical
      assessment not only for risk stratification but also in order to guide the
      prescription of new pharmacological and non-pharmacological therapies.

PMID- 11582720
TI  - [The neurovegetative system in heart failure and heart transplantation].
AB  - Increased sympathetic activity and plasma levels of norepinephrine,
      parasympathetic withdrawal and impaired baroreflex gain have been reported in
      patients with chronic heart failure (CHF). Since excessive neurohormonal
      activation is implicated in the progression of heart failure, it is crucial to
      measure and quantify it in clinical practice. Some techniques that may be
      suitable for this purpose such as catecholamine plasma level assessment or direct
      recording of the neural efferent activity to the peripheral muscles, require
      expertise and are very unattractive in terms of cost-effectiveness. On the
      contrary, the measures that test the reflex or tonic responses of the sinus node
      activity have been extensively used in both experimental and clinical studies.
      However, consensus regarding their true relevance in the clinical scenario has
      not yet been reached. Heart rate variability is one of the easiest techniques
      available for physicians but the identification of the RR intervals in CHF is
      often very difficult owing to the presence of rhythm disorders or of sino-atrial
      or atrioventricular blocks and the analytical softwares included in the
      commercially available Holter systems are not reliable enough. Similarly, for all
      methods currently employed in clinical practice, the assessment of baroreflex
      sensitivity in CHF has some limitations or is not applicable for all patients. In
      this article, the main clinical methods used to assess the autonomic nervous
      system in CHF are reviewed focusing on the clinical applicability of the obtained
      parameters. It is underlined that, using these techniques, many investigators
      have obtained important results in the pathophysiological comprehension of the
      disease, but to date their use in the clinical setting is very modest. Indeed,
      before the measurement of the autonomic nervous system can be applied to clinical
      practice and used to guide therapy, more precise insights into the link between
      the autonomic indexes and sympathetic or parasympathetic activity and between
      them and mortality are needed. Moreover, no standardization has been established
      for the various commercial systems and the development of their software has not
      been guided by any research committee. For many other techniques there are no
      commercially available devices and the software has been developed in the
      physiological laboratories as prototypes. These limitations will be overcome if
      the researchers succeed in convincing the companies about the importance and the
      clinical applicability of the evaluation of the autonomic nervous system. With
      regard to cardiac transplantation, as the donor heart is completely denervated,
      it constitutes an important physiological model for the study of autonomic
      activity. The more interesting research field has been the assessment of a
      possible post-transplant reinnervation both at the experimental and clinical
      levels. It has been shown that in animal models reinnervation occurs within the
      first year of heart transplantation. Several authors have demonstrated a time
      dependent restoration of myocardial norepinephrine content as well as an increase
      in the heart rate and myocardial contractility in response to neural sympathetic
      stimulation. Parasympathetic efferent reinnervation has also been demonstrated in
      a canine transplanted model within 12 months of surgery. Despite evidence in
      favor of both sympathetic and parasympathetic reinnervation in animals, the
      problem of whether such reinnervation also occurs in humans is still debated,
      especially as far as parasympathetic reinnervation is concerned. The presence, in
      humans, of sympathetic reinnervation has been documented by different methods.
      However, there are significant differences regarding the degree of regeneration
      and the frequency of occurrence. It has also been assumed that the regeneration
      of sympathetic fibers takes place slowly over time. In contrast, regrowth of
      parasympathetic nerve fibers in patients after heart transplantation has not been
      unequivocally confirmed. Although various investigators have used the same
      method, their results differ and are indeed often contradictory. Recently it has
      been suggested that the type of surgery may have a major influence on neural and
      particularly parasympathetic regeneration. If the patients undergo heart
      transplantation by bicaval techniques the nerves are resected and they are more
      prone to regenerate towards the donor heart. This is not true if the traditional
      technique is employed.

PMID- 11582721
TI  - [Comparison of clinical and electrophysiologic characteristics of patients with
      occult and manifest atrioventricular accessory pathway].
AB  - BACKGROUND: It is current opinion that concealed and manifest accessory pathways
      (APs) are indistinguishable with respect to their location and contribution to
      orthodromic reciprocating tachycardias. The aim of this study was to compare
      clinical and electrophysiological characteristics of two groups of patients.
      METHODS: Between January 1999 and June 2000, 42 consecutive patients underwent
      radiofrequency catheter ablation for paroxysmal atrioventricular reciprocating
      tachycardia attributable to a concealed AP. Their clinical and
      electrophysiological characteristics were compared with a group of 48 consecutive
      patients with manifest AP and supraventricular tachyarrhythmias. RESULTS: There
      were no differences regarding gender, the prevalence of heart disease and the age
      of onset of symptomatic tachycardias between the two groups. Compared to those
      with a manifest AP, the patients presenting with a tachyarrhythmia due to a
      concealed AP were older (48 +/- 15 vs 40 +/- 16 years, p < 0.05) and had a longer
      history of tachyarrhythmias (22 +/- 16 vs 13 +/- 13 years, p < 0.05). Atrial
      fibrillation was more frequent in patients with a manifest AP than in patients
      with a concealed AP (50 vs 9.5% respectively, p = 0.02). Atrioventricular
      reciprocating tachycardia was a cause of more hospitalizations (76 vs 35%, p =
      0.01) and episodes of pre-syncope (47 vs 22%, p < 0.05) in the group of patients
      with a concealed AP. The anatomical site of concealed and manifest APs was
      significantly different: concealed APs were more frequently localized in the left
      side (93% left, 7% right), while manifest APs were seen in the left side in 64%
      of cases, in the right side in 29% and in the posteroseptal left + right region
      in 7% of cases. The retrograde electrophysiological properties and the
      inducibility of other types of reentrant arrhythmias were similar. Catheter
      ablation was similarly successful regardless of whether the AP was concealed or
      manifest, the rates of success being 91 and 88% respectively at the first attempt
      and with a similar number of energy applications (7 +/- 7 vs 10 +/- 9, p = NS).
      At a second attempt, the procedure was successful in 100 and 98% of cases
      respectively. Periprocedural complications occurred in 5% of patients with a
      concealed (1 ventricular fibrillation, 1 cerebral transient ischemic attack) and
      in 8% of patients with a manifest AP (2 pericardial effusion, 1 transient
      atrioventricular block, 1 anginal attack with spontaneous recovery) (p = NS).
      Complications occurred only for left-sided APs and were independent of the
      approach (transseptal or retrograde). Relapse of AP conduction was more frequent
      in the group of patients with a manifest than in those with a concealed AP (12 vs
      5%), though not significantly. There were no late complications. CONCLUSIONS:
      Those patients presenting with a tachyarrhythmia due to a concealed AP, compared
      to those with a manifest AP, were older and had a longer history of
      tachyarrhythmia. Atrial fibrillation was more frequent in patients with manifest
      AP. Atrioventricular reciprocating tachycardia episodes were longer-lasting and
      caused more hospitalizations and more frequently pre-syncope in the group of
      patients with a concealed AP. Almost all concealed APs were localized in the left
      side. The retrograde electrophysiological properties were similar. The results of
      radiofrequency catheter ablation were comparable in both groups.

PMID- 11582722
TI  - [Aortocoronary bypass in severe left ventricular dysfunction: 9 years of clinical
      experience and mid-term results].
AB  - BACKGROUND: Compared with medical therapy alone, coronary artery bypass surgery
      improves survival in patients with coronary disease and left ventricular
      dysfunction. Many of these patients have a hibernating myocardium secondary to
      chronic ischemia with the potential for improvement in left ventricular function
      and heart failure symptoms following revascularization therapy. Cardiac
      transplantation remains the treatment of choice for patients with severe
      congestive heart failure. METHODS: From January 1992 to June 2000, 351
      consecutive patients (318 men, 33 women, mean age 62.8 +/- 8.9 years) with a left
      ventricular ejection fraction (EF) < or = 35% and with multivessel coronary
      artery disease underwent isolated coronary artery bypass grafting. Preoperatively
      226 patients were in CCS class III-IV and 113 in NYHA class III-IV. The mean
      number of grafts was 3.4 +/- 0.8/patient and complete revascularization was
      achieved in 98.6% of cases. The internal mammary artery was used in 341 patients
      (97.2%) and in 328 (96%) as a graft for the left anterior descending artery.
      Follow-up was obtained in 97% of the patients and on average lasted 42 +/- 28
      months. RESULTS: The hospital mortality was 5.9%. At multivariate analysis urgent
      operation (p < 0.01) and a lower EF (25.9% in deaths vs 29.1%, p < 0.05) were
      predictors of an increased operative mortality. EF (assessed postoperatively at
      transthoracic echocardiography in survivors) improved from 28.9 +/- 5.7 to 34.4
      +/- 7.7% (p < 0.0001). At 1, 3, 5, 7, and 9 years respectively, the all-cause
      survival was 93 +/- 1.5, 85 +/- 2.2, 77 +/- 3.1, 69 +/- 4.9, and 60 +/- 7.3% and
      the freedom from cardiac death was 94 +/- 1.4, 89 +/- 1.9, 88 +/- 2, 80 +/- 4.7,
      and 76 +/- 5.7% with an improvement in the anginal and congestive heart failure
      status (p < 0.0001). CONCLUSIONS: In patients with coronary artery disease and
      severe left ventricular dysfunction, after evaluation of the clinical
      presentation, of the usefulness of vessels as grafts and of the presence of
      myocardial viability, 1) coronary artery bypass grafting can be performed with a
      low mortality and a good mid-term survival, 2) improvement in left ventricular
      function can be documented after coronary bypass surgery, 3) the internal mammary
      artery can be safely used as a graft, 4) the quality of life is improved as
      demonstrated by the improvement in the anginal and congestive heart failure
      status.

PMID- 11582723
TI  - [Early diastolic sound in a patient with hepatocarcinoma].
AB  - On physical examination an early diastolic sound is usually associated with
      mitral stenosis, prosthetic mitral valve replacement and chronic constrictive
      pericarditis. In case of an atrial myxoma, an early diastolic sound can be
      usually heard due to movement of the tumor towards the tricuspid valve (tumor
      plop). The following case report shows an example in which an early diastolic
      sound was heard in a patient presenting with a hepatocellular carcinoma. This
      sound was due to the presence of a thrombus that originated from the inferior
      vena cava and invaded the right atrium up to the tricuspid valve. It was thus
      similar to an atrial myxoma and produced a tumor plop.

PMID- 11582724
TI  - [Recurrent episodes of acute non-cardiogenic pulmonary edema caused by ingesting
      hydrochlorothiazide].
AB  - We describe a case of a patient presenting repeated episodes of sudden-onset
      pulmonary edema each occurring immediately after the ingestion of
      hydrochlorothiazide. The close temporal relationship between the ingestion of
      hydrochlorothiazide and the onset of symptoms together with the rapid and full
      clinical recovery after the interruption of therapy, allowed the diagnosis of
      drug-induced pulmonary edema and a possible anaphylactoid hypotension. The
      initially low white blood cell count, associated with hemoconcentration, and the
      increase in white blood cells during the following 24 hours, is consistent with
      the hypothesis of intrapulmonary sequestration of granulocytes causing pulmonary
      edema. The pathogenesis and the cause of the increased pulmonary sensitivity are
      reviewed and discussed.

PMID- 11582725
TI  - [Usefulness of implantable loop recorder in the diagnosis of undetermined
      syncope. Report of a clinical case].
AB  - In this paper we describe the case of a 42-year-old man who presented with rather
      infrequent episodes of syncope. In view of this symptomatology, he had been
      repeatedly hospitalized and submitted to a complete diagnostic workup inclusive
      of brain computed tomography, head-up tilt test, repeated Holter monitoring, and
      electrophysiologic evaluation. Unfortunately, none of these tests allowed the
      formulation of a precise diagnosis. When, owing to further episodes of syncope,
      the patient came to our observation, after an inconclusive new series of
      noninvasive tests, we decided to implant an insertable loop recorder. This device
      revealed that a phase of severe bradycardia lasting 53 s, with 15 s of complete
      asystole, occurred during symptoms thus allowing us to diagnose the cause of
      syncope.

PMID- 11582726
TI  - [Effects of multisite biventricular pacing in patients with heart failure and
      intraventricular conduction delay].

PMID- 11582727
TI  - [Comparison of coronary-artery bypass surgery and stenting for the treatment of
      multivessel disease].

PMID- 11582728
TI  - [Efficacy and safety of thrombolytic therapy after initially unsuccessful
      cardiopulmonary resuscitation: a prospective clinical trial].

PMID- 11582729
TI  - [Effect of carvedilol on survival in severe chronic heart failure. A trial of the
      beta-blocker bucindolol in patient with advanced heart failure].

PMID- 11582730
TI  - [Unheard of paradox: role of fish in the diet of the post-infarction patient].

PMID- 11582731
TI  - [Role of beta-blockers in the treatment of chronic heart heart failure].
AB  - Role of beta-blockers in the treatment of chronic heart failure has been changed
      over a 25-year period from contraindication to an established indication. To
      date, controlled clinical trials performed in more than 13,000 patients with
      chronic heart failure have consistently shown that the long term administration
      of beta-blockers is associated with significant improvement in left ventricular
      function, clinical symptoms, and survival. This favorable clinical trial
      experiences support a recommendation that beta-blockers should be used in all
      heart failure patients with stable symptoms due to left ventricular systolic
      dysfunction unless contraindicated. Ongoing beta-blocker studies address further
      new topics, such as treatment of elderly patients and direct comparison of
      different agents. Although, the use of beta-blockers for heart failure tends to
      increase, implementation of the experiences from the clinical trials to the
      everyday practice still remains a challenge.

PMID- 11582732
TI  - [Prognostic significance of retinal microaneurysm number and localization in type
      1 diabetes mellitus].
AB  - The authors studied whether central retinal microaneurysm count predicts further
      progression of background retinopathy in juvenile onset type-1 diabetes mellitus.
      94 patients (49 females and 45 males) were followed up longitudinally (8-17.5,
      mean 10 years) by evaluating fluorescein angiograms. Age at last examination was
      17-32 years (mean age 22.4 years) and duration of diabetes was 8-22 years (mean
      duration 13.7 years). Microaneurysm counts and location were determined with the
      help of a grid consisting of three concentring circles and four radial lines
      (nine subfields) centered for the macula. 82% of the all microaneurysms were
      found inside the circle with 1500 micron radius. Participants were divided into
      three groups: those with no microaneurysms (1st group, n = 28) and those with 1-4
      (2nd group, n = 35) and those with 5 or more microaneurysms (3rd group, n = 31)
      in the central circle with 600 micron radius at least one time during the whole
      follow up. Background retinopathy was found in 3 of 28 cases (approximately 10%)
      in the first group, 8 of 35 (approximately 23%) in the second group and in all
      the 31 patients (100%) in the third group. Proliferative retinopathy was found in
      the third group only. The authors suggest that the appearance of 5 or more
      microaneurysms in the macular area in type-1 diabetes mellitus may be sensitive
      indicator of the development of severe background and proliferative retinopathy.
      Study describes the importance of central microaneurysm count predicting further
      progression of background retinopathy could not be found in the available
      literature.

PMID- 11582733
TI  - [Interferon-alpha and PUVA therapy for mycosis fungoides].
AB  - 14 patients suffering from early stage mycosis fungoides were treated with
      interferon alpha 2-a and PUVA/1 patient in stage I a, 3 patients in stage I b, 4
      patients in stage II a and 6 patients in stage II b/during 3-21 months time
      course. Interferon alpha 2-a was administered 3 times a week, in escalating dose
      from 3 MU to 9 MU, determining the individual maximal tolerated dose. All of the
      patients responded well to the treatment. Partial remission was observed after 4
      13 weeks of treatment. Total remission developed in 8 cases, after 8 weeks- 9
      months of the treatment. Side effects occurred frequently: weight loss, pain,
      fever, fatigue, leucopenia, thrombopenia, liver enzyme elevation. Because of the
      side effects the dose of the interferon was reduced individually, the dose
      reduction did not cause relapse.

PMID- 11582734
TI  - [Scientometric and publication malpractices. The appearance of globalization in
      biomedical publishing].
AB  - Attention is drawn to publication and scientometric malpractices utilized by
      biomedical authors who do not adhere to the accepted ethical norms. The
      difference between duplicate/redundant and bilingual publications is defined. In
      the course of discussion of the manipulations that may be observed in the field
      of scientometry, it is pointed out that abstract of congress lectures/posters can
      not be taken into consideration for scientometric purposes even if such abstracts
      are published in journals with impact factors. A further behavioral form is
      likewise regarded as unacceptable from the aspect of publication ethics: when a
      physician who has participated in a multicentre, randomized clinical trial
      receives recognition (in an appendix or in an acknowledgement of an article) as
      having contributed data, but assesses this appreciation as co-authorship and
      thereby attempts to augment the value of his or her publication activity. The
      effects of globalization on biomedical publication activity are considered, and
      evidence is provided that the rapidly spreading electronic publication for a give
      rise to new types of ethical dilemmas. It is recommended that, in the current age
      of Anglo-American globalization, greater emphasis should be placed on the
      development of medical publication in the mother tongue (Hungarian).

PMID- 11582735
TI  - [Term pregnancy with fetus papyraceus].
AB  - The authors describe a case of dichorionic-diamniotic twin gestation diagnosed in
      the first trimester. One of the twins perished during the 2nd trimester and
      became compressed against the uterine wall (stuck twin phenomenon). The surviving
      sibling weighing 3400 g was delivered by cesarean section at term in good
      condition along with the placenta. A much smaller, pale second placenta was
      extracted thereafter together with a hardly recognizable fetus papyraceus.

PMID- 11582736
TI  - [Quantitative detection of HER-2 oncogene amplification in primary hepatocellular
      carcinoma using dual FISH technique and its clinical significance].
AB  - To investigate the frequency of HER-2 oncogene amplification in primary
      hepatocellular carcinoma (HCCs) and its relationships with clinicopathological
      parameters and prognosis, 42 surgical samples from patients with primary HCCs
      were detected for their HER-2 oncogene amplification by dual FISH technique, and
      then the correlations between HER-2 amplification and clinicopathological
      characteristics and prognosis were analyzed statistically. HER-2 oncogene
      amplification was detected in 9 of 42 (21.4%) primary HCCs, including 4 (9.5%)
      cases with high copy (HC) and 5 (11.9%) ones with low copy (LC). HER-2
      amplification was associated significantly with postoperative survival time of
      HCC patients examined (P = 0.046) and the presence of HER-2 gene amplification
      showed a trend toward a correlation with tumor size (P = 0.085), but wasn't
      relative to sex, age, AFP level, HBV infection, postoperative relapse and
      clinical staging of HCC patients tested (P > 0.05). On the other hand, gain of
      the HER-2 oncogene copy was examined in 31 of 42(73.8%) primary HCCs, consisting
      of 9 (21.4%) cases with HER-2 amplification and 22(52.4%) ones with aneusomy
      17/polysomy 17. There weren't significant relationships between gain of HER-2
      oncogene copy and, HCC patient's sex, tumor size, clinical staging, postoperative
      relapse and survival time (P > 0.05), but gain of HER-2 oncogene copy correlated
      significantly to patients' age, AFP level and HBV infection (P < 0.05). The study
      indicated that there were a lower frequency of HER-2 oncogene amplification and a
      higher frequency of aneusomy 17/polysomy 17 in primary HCCs and that HER-2
      oncogene amplification activation might be involved in the development and
      progression of a subset of HCCs, and seemed to be a valuably independent
      prognosis factor predicting postoperative poorer survival for patients with HCC.

PMID- 11582737
TI  - [Genetic analysis of important growth trait based on F-2 resource population in
      chicken].
AB  - A three-generation of chicken population is being constructed for mapping multi
      economical trait loci where three extremely divergent breeds, including a broiler
      breed(A), a layer breed(B) and white-silk chicken(C) were employed for reciprocal
      cross. Four cross combinations of A Male x C Female, C Male x A Female; B Male x
      C Female, C Male x B Female were performed with 277 individuals in total parental
      population. According to the statistic analysis for growth trait, difference
      between parental lines is significant, F2 generation attains great variation.
      Correlations among body weight and daily gain traits are significant and relative
      coefficient are moderate or high. The number at QTL loci is expected to be no
      more than 10, and based on the theoretical computation the sample size of this
      resource population is sufficient for QTL mapping.

PMID- 11582738
TI  - [Expression pattern of mRNA for follistatin and inhibin/activin beta B-subunit
      during follicular and testicular development in duck].
AB  - Follistatin and inhibin/activin were closely related glycoprotein hormones. The
      quantitative competitive RT-PCR was used to investigate the expression of
      follistatin and inhibin/activin beta B-subunit mRNA in the developing ovarian
      follicles, immature and mature testes. The results revealed all samples showed
      the expression of mRNA for the two proteins, and the expression is more
      abundantly in the small follicles than in the large preovulatory follicles.
      Competitive RT-PCR revealed that the expression of follistatin is the highest in
      small yellow follicles (SYF), the mean relative content for the F1, F2, F3, F4,
      F5, F6-8, LWF (large white follicle), TI(immature testes), and TM(mature testes)
      was 0.011 +/- 0.004, 0.019 +/- 0.006, 0.021 +/- 0.009, 0.028 +/- 0.007, 0.075 +/-
      0.023, 0.15 +/- 0.072, 0.29 +/- 0.068, 0.037 +/- 0.011, and 0.012 +/- 0.004,
      respectively, compared to a mean relative content of 1.00 for the SYF. The
      highest level of inhibin/activin beta B mRNA was also found in the SYF, the mean
      relative content for the F1, F2, F3, F4, F5, F6-8, LWF, TI, and TM was 0.009 +/-
      0.003, 0.013 +/- 0.005, 0.019 +/- 0.007, 0.023 +/- 0.006, 0.29 +/- 0.084, 0.84 +/
      0.093, 0.031 +/- 0.008, 0.38 +/- 0.072, and 0.046 +/- 0.013, respectively,
      compared to a mean relative content of 1.00 for the SYF. Our data suggested that
      the expression pattern of mRNA for follistatin and inhibin/activin beta B-subunit
      was quite similar during follicular and testicular development. The great co
      expression of mRNA for the two proteins in small follicles indicated that activin
      B(beta B-beta B) availability was tightly regulated by follistatin, and the two
      proteins might both play important roles in early follicular development.

PMID- 11582739
TI  - [The specific labelling of mouse embryonic stem cells].
AB  - Despite the wide application of ES cell technology, little is known about the
      pluripotent nature of ES cells. This is partly due to the heterogeneity of ES
      cell population in culture. This report described the specific labelling of
      undifferentiated cells in ES cell lines. oct-4 gene is specifically expressed in
      all the totipotent cells in mouse embryos and undifferentiated ES cells. A
      constructed pG18NG was obtained by inserting the reporter gene beta geo into the
      oct-4 transcription elements. ES cell lines MESPU22 and MESPU13 were transfected
      with this construct and stable integrated cell clones were selected out. With the
      experiments of in vitro cultivation, differentiation and chimeras production, it
      was confirmed that we have successfully labelled the undifferentiated cells in ES
      cell lines, and this label was both valid in vitro and in vivo.

PMID- 11582740
TI  - [Detection of Cre recombinase activity in Mx-Cre transgenic mice induced by INF
      in vitro].
AB  - The Cre recombinase and its activity in C57-TgN(Mx-Cre) transgenic mice is
      studied by polymerase chain reaction (PCR), Western blot, immunohistochemistry,
      immunogold electron microscopy and Southern blot. C57-TgN(Mx-Cre) transgenic mice
      harbouring cre gene in genomic DNA is demonstrated by PCR, and these mice which
      are induced by INF-alpha 1b could express Cre recombinase, which is confirmed by
      Western blot. With immunohistochemistry, we find that the Cre recombinase
      expresses in hepatocyte cytoplasm and nuclear of C57-TgN(Mx-Cre) transgenic mice.
      Cre recombinase expressed in hepatocyte cytoplasm and nuclear is further
      confirmed by immunogold electon microscopy. And it is supported that the Cre
      recombinase which is created from C57-TgN(Mx-Cre) transgenic mice induced by INF
      alpha 1b can direct DNA recombination reaction in vitro. All evidence leads us
      supporting the view that the Cre recombinase expressed in C57-TgN(Mx-Cre)
      transgenic mice has activity. Thus we find a method to detect the activity of Cre
      recombinase in vitro.

PMID- 11582741
TI  - [Localization and position effect of human APPSWE gene on transgenic mice by
      means of in situ fluorescence hybridization].
AB  - In situ fluorescence hybridization (FISH) was used to study the integration and
      localization of human APPSWE gene on chromosomes of transgenic mice. It was found
      that in 2 founder mice, 34 and 36 metaphases of 80 metaphases observed had shown
      obvious specific hybridizing signals, the detection rates were 42.5% and 45%,
      respectively; meanwhile, in 1 F1 and 1 F2 mice, 33 and 30 metaphases out of 100
      metaphases observed had specific hybridizing signals, the detection rates were
      33% and 30%, respectively. The transgenes were localized on chromosome 8, 1, 17
      and 2. The results indicated that transgene APPSWE were integrated stably into
      the chromosomes of transgenic mice and could be transmitted to offsprings through
      germ cells. The transgenes were randomly integrated into multiple sites of mice
      chromosomes. Meanwhile, the phenotypes of transgenic mice were also studied and
      different integrated sites had obvious effects on the pheonotypes.

PMID- 11582742
TI  - Cloning and sequence analysis of 5' fragment of Hoxa-11 gene in Latimeria
      chalumnae.
AB  - Hoxa-11 gene is essential for the development of fish fins and tetrapod limbs.
      Based on the published nucleotide sequences of human and mouse Hoxa-11 genes, two
      degenerate primers were designed. Latimeria Hoxa-11 gene fragment was amplified
      by PCR, cloned and sequenced. The acquired Hox gene fragment, which encodes 204
      amino acids, is comprised of 2,065 bp, including most exon 1, intron and partial
      exon 2. The homology of latimeria Hoxa-11 protein is 66.0% to human, 67.6% to
      mouse, 74.4% to chick, 72.8% to frog, and 59.7% to zebrafish, respectively. The
      exon 2 region including the homeobox and the splice site are highly conserved.
      However, the exon 1 region has increased in size by 16% from latimeria to human.
      Sequence analysis further revealed that exon 1 of latimeria Hoxa-11 could be
      divided into four regions: two highly conserved regions, a moderately conserved
      region, and a variable region adjacent to the intron. The size variation is
      primarily caused by the accumulation of alanine repeats and of flanking segments
      rich in glycine and serine in the variable region. It implies that the variable
      region might be related to acquisition of new functions in the fin-limb
      transition and vertebrate evolution. Besides the homeobox, two highly conserved
      regions in exon 1 and two phylogenetic footprints in the intro were found. The
      strong sequence conservation suggests an important functional role of these
      regions.

PMID- 11582743
TI  - [Analysis on single nucleotide polymorphisms of porcine myostatin gene in
      different breeds].
AB  - By PCR-RFLPs and PCR-SSCP approach, three single nucleotide polymorphisms (SNPs)
      of porcine myostatin gene (MSTN) were analyzed in different breeds including
      "doubled-muscled" Yorkshire, Yorkshire, Landrace, Hamshire, Duroc, Piteran,
      Erhualian, Min, Hubei White and some hybrids. The three SNPs were located in the
      3' encoding region, 5' promoter region and intronl region respectively. For the
      SNP in the 3' encoding region, which was caused by C-->T transition, the mutation
      frequency was relatively low: no TT genotype was detected in 274 individuals of
      different breeds. For the SNP in the 5' promoter region, 560 pigs were
      investigated. The allele T dominates in the imported lean-type pig breeds such as
      Yorkshire, Landrace, Duroc, Hampshire, Piteran and hybrid, however, in Erhualian
      and Hubei White pigs, the allele A was in majority. Polymorphism showed the
      similar pattern for the SNP in intron 1 region. G was the dominant allele in
      Yorkshire, Landrace and their hybrids, while in Erhualian and Hubei White pigs
      the frequency of A was much higher. Obviously they were not in Hardy-Weinberg
      equilibrium state. For Min and Yorshire x Erhualian pigs, they were in Hardy
      Weinberg equilibrium state for the SNPs in the 5' promoter region and (or) intron
      1 region. The frequency for the A alleles of SNPs in the 5' promoter region and
      intron 1 region was higher for "double-muscled" Yorkshire than for Yorkshire and
      linkage for these two mutation sites was also observed.

PMID- 11582744
TI  - [Genetic analysis of cry1Ab gene of Bt rice].
AB  - Improved histochemical staining for GUS activity, PCR and Western blotting were
      used to analyse the progeny population of Bt rice crossed with conventional rice
      varieties. A total of 392 plants expressing Bt toxin protein were found in 394
      GUS positive plants. The result demonstrated that cry1Ab gene closely inherited
      and expressed with reporter gene gus. GUS assays indicated that cry1Ab gene of Bt
      rice inherits as a single dorminant gene. Southern hybridization confirmed cry1Ab
      gene can inherit stabily in the progenies of Bt rice. Mendelian segregation of
      reporter gene gus was also observed in F2, BC1 and BC1F2 progenies, which
      indicated that cry1Ab gene inherits as a single dorminant gene in the progenies
      of Bt rice crossed with conventional rice varieties.

PMID- 11582745
TI  - [Detection of the wheat salt-tolerant-mutant using PCR-SSCP combining with direct
      sequenceing].
AB  - gf-2.8 is a gene located on the chromosomal homologous group 4, which was
      reported to have relationship with salt tolerance of wheat. A pair of primers
      were designed to amplify the coding region of gf-2.8 in the two salt-tolerant
      mutants and their parents. Agarose gel electrophoresis showed that the 685 bp
      band was amplified among all the materials. SSCP analysis suggested that 974915
      (one of the mutants) was different from the other materials. The sequencing
      results showed that Jimai 24 and its salt-tolerant mutant 8901-17 had the same
      sequence as published, which indicated that the mutation site of 8901-17 was not
      on the gf-2.8 gene. However, there were at least two single base mutations in the
      gf-2.8 of 974915, one of which caused the alternation of amino acid, this
      mutation occurred in the conservative region of gf-2.8.

PMID- 11582746
TI  - [Application of molecular markers-assisted selection of wx genes in breeding the
      waxy wheat].
AB  - Chinese Spring and its null-tetrasomic lines were used to identify the specific
      bands of STS-marker and microsatellites (SSR) marker of wx genes. Twelve
      varieties and five waxy wheat lines were screened with these two markers, and the
      results are in agreement with those from Wx subunits SDS-PAGE. A F2 segregating
      population from cross Jiangsu Baihuomai x Kanto 107 was also detected by
      molecular markers, not only eight wx genotypes were developed while three
      genotypes did not exist in the nature, but also the first batch of waxy wheat
      lines were bred. The Jiangsu Bainuomai improvement population was screened, and
      six 7D momosomic plants with wx-D1b were obtained, which could provide materials
      for waxy wheat breeding. Application molecular markers of wx genes will improve
      the selection procedure for the waxy wheat and good noodle-quality wheat.

PMID- 11582747
TI  - [Chromosomal location and molecular marker of resistance gene to Puccinia
      striiformis west. in Leymus mollis Trin. Hara].
AB  - The hybrid wheat line, 93784 is a stable line selected from progenies of Leymus
      molli Trin. Hara x common wheat, which shows a very high level of resistance to
      yellow rust. The results of GISH using genomic DNA of Leymus mollis as probe
      indicated that the 93784 was a wheat-Leymus mollis small segment translocation
      line, and the translocated alien chromosome fragment were located on a pair of
      short arm terminals of what chromosomes. Using this translocation line, we
      established F2 segregation population and identified its yellow rust resistance
      in adult stage. Genetic analysis suggested that the yellow rust resistance of
      93784 was controlled by a single gene. The gene was located on the translocated
      chromosome segments of Leymus mollis. We called it YrLm. By AFLP analysis with
      Taq I (T1-T4)/Pst I (P1-P6) primes in individuals of F2 segregation population
      and their susceptive and resistant parents, we screened a molecular marker that
      linked to yellow rust resistance gene YrLm. We also cloned and sequenced the
      molecular marker. The length of the marker is 205 bp, named P1T(3)205.

PMID- 11582748
TI  - [Construction of genetic map in sorghum and fine mapping of the germination
      stimulant production gene response to Striga asiatica].
AB  - Sorghum is the fifth important crop in the world. It is also the major food
      resource in African countries. Striga asiatica is a parasitism weed on sorghum
      and some other important crops. In this report, two sorghum lines with the
      difference in response to Striga asiatica, SRN39 (lower Germination Stimulant
      GermStim production) and Shanguihong (high GermStim production), were selected as
      the parents for the construction of a recombinant inbred (RI) population. Ninety
      four RI lines were collected for the molecular analysis and GermStim production
      evaluation. A genetic map was constructed with 251 molecular markers that
      distributed on 10 different linkage groups. The map covers sorghum genome of
      1,779 cm with an average map distance of 7.1 cm between linked markers. It is one
      of the complete sorghum molecular map in the world. Co-segregation analysis
      indicated that the germination stimulant gene (GermStim) was located on linkage
      group J, which was at a distance of 13 cm from the closed marker. Further RAPD
      analysis between two parents and two DNA pools different in the amount of
      germination stimulant production, several polymorphic DNA fragments were
      identified and cloned. Mapping results showed two of them flanked with the
      GermStim gene at a distance of 1.6 cm and 2.1 cm respectively.

PMID- 11582749
TI  - [Genetic analysis of T1 progeny of transgenic tobacco with metallothionein gene
      and metallothionein domain mutant alpha alpha gene].
AB  - The chimeric gene containing a cloned mouse metallothionein processed gene or a
      cloned mouse metallothionein domain mutant alpha alpha gene was respectively
      introduced into tobacco (Nicotiana tobacum L. cv. NC89) on a disarmed Ti-plasmid
      of Agrobacterium tumefaciens. T1 seeds from self-fertilized transgenic tobacco
      were germinated on media containing cadmium or herbicide PPT. The PPT tolerance
      trait followed Mendelian inheritance and co-segregated with heavy metal
      tolerance. Meanwhile Southern blot and Western blot verified the existence of the
      MT gene and alpha alpha mutant gene in the T1 generation plants which keep
      tolerance to heavy metal. All the results demonstrated the stable integration and
      inheritance of exotic genes. In addition, assay of the root length and fresh
      weight of T1 seedlings indicate that transgenic tobacco plants with alpha alpha
      mutant gene still have a little higher tolerance than that with matural MT gene.

PMID- 11582750
TI  - [Historical dynamics of life-span distribution of Man].
AB  - In this activity the historical dynamics of life-span distribution parameters of
      the people was investigated in 12 developed countries encompassing the period of
      1750-1998 years, it is treated about 1200 life tables. The approximately of a
      linear segment of a curve of age-specific death rate by the Gompertz function
      allows getting an analytical view of the life-span distribution. It is shown that
      the decreasing of the lower age range since 35 years till 10 years a little bit
      augments an approximation error. The Stehler-Mildvan correlation parameters are
      computed for each country, for each year during all indicated period. Estimations
      of the average life, modal age, dispersion etc. are obtained. It draws a
      conclusion about the limitation and stabilization of modal age at preservation of
      existing regularity in dynamics of the life-span distribution parameters.

PMID- 11582751
TI  - [A.A. Malinovskii and significance of the system approach in gerontology].
AB  - A.A Malinovsky allocated 4 most important principles of the system theory:
      discreteness/rigidity of system, presence of feedback, occurrence of new
      properties at association of elements in system, a continuity and the maximal
      fitness in evolution. He believed that the essential factor determining life
      longevity of the individual are his species-specific characteristics. A.A.
      Malinovsky together with coworkers has revealed the attributes most connected to
      increase of terms of life: a high degree of the cephalization and the big sizes
      of a body. He also emphasized, that with an exit on a high intellectual level
      people have occupied especially position at which the biological factors
      influencing life longevity, began to lose paramount signification, value of long
      life has increased. The increase of life longevity has resulted in the important
      consequence--to increase of the number of diseases at late age. The diseases with
      hereditary predisposition have got the big weight. A.A. Malinovsky considered 4
      basic levels of a condition of functions of an organism. The level of the maximal
      pressure--mobilization of all forces of an organism on type of "emergency alarm",
      promotes wear process of an organism and disorder of its separate functions.
      Damage of the weakest link translates an organism from a stable condition in
      pathological when the depression of one function reduces a level of others which
      in turn, even more can suppress the first, resulting in to a vicious circle (a
      positive feedback). A.A. Malinovsky has entered concept about increasing
      "disregulation" of the functions of an organism during ageing as to the main
      reason limiting human life. He assumed, that such rigid system (organism) which
      has strong link (subsystem), and other subsystems function approximately at one
      level has the greatest stability. It is possible, that presence of weakest links
      is connected to size of a genetic load. Our paper demonstrates the importance of
      A.A. Malinovsky system approach for such field of knowledge as gerontology.

PMID- 11582752
TI  - [On possible role of chaotic behavior of the gene regulation system in aging].
AB  - 1. The facts of biology of aging say that the modification of activity of few key
      genes may lead to the significant increase of life span. 2. The experiments with
      computational models of gene regulation show that these models are characterized
      by metastable behavior typical for the chaotic systems. 3. The force of mortality
      in Gompertz equation grows exponentially in time. It allows to hypothesize that
      at least at the level of gene regulation aging can be a chaotic process (here
      implied that chaos is a kind of the complex systems dynamics controlled by
      strictly determined rules). This approach allows to describe aging from the view
      point of the information theory--as the forgetting of the right functioning of
      the organism (i.e. forgetting the state of health) caused by fluctuations (weak
      nonspecific influencies on the system). Average rate of such forgetting
      (described by parameter, named Lyapunov exponent) could be identified with the
      exponent of mortality rate in Gompertz equation. And the parameter inverse to
      Lyapunov's exponent (Lyapunov time), that describes the time of the initial
      (healthy) state forgetting, well corresponds to the time of the puberty beginning
      (i.e. the minimal time for the healthy state to be kept) for human beings, mice,
      and fruit flies (organisms whose parameters of aging are most perfectly known).

PMID- 11582753
TI  - [Human chromosome functional characteristics and aging].
AB  - The MUTATION level (chromosome aberrations covering telomere regions),
      MODIFICATIONS of CHROMOSOME STRUCTURE (level of condensed chromatin identified by
      the methods of electron microscopy and differential scanning microcalorimetry;
      level of C-banding constitutive heterochromatin; transcriptional activity of DNA
      dependent RNA polymerase; Ag-positive NORs and associations of acrocentric
      chromosomes) and REPARATION (intensity of unscheduled DNA synthesis and the
      frequency of sister chromatid exchanges) have been studied in lymphocyte cultures
      from individuals at the age of 70-114 to reveal the chromosome functional
      organization at late stages of ontogenesis and to find explanations of some
      senile pathologies. The analysis of obtained results showed: 1) chromosome
      progressive heterochromatinization (condensation of eu- and heterochromatin
      regions) occurs at aging; 2) decrease of repair processes and increase in
      frequency of chromosome aberrations in aging are secondary to the progressive
      heterochromatinization. Chromosome heterochromatinization is a key factor of
      aging; 3) chromosome heterochromatinization may be the reason for some senile
      pathologies; 4) chromosome heterochromatinization is an area where one should
      seek the ways for prolonging the lifespan.

PMID- 11582754
TI  - [Spontaneous mutagenesis in different strains of mice during aging].
AB  - The article is devoted the problem of mutagenesis during aging. There is
      identical affirmative dynamics of chromosome aberration frequencies in male of
      transgenic and control non-transgenic mice of age. Spontaneous chromosome
      aberration frequencies in somatic cells in young age differ in transgenic and
      control mice more, than in older mice.

PMID- 11582756
TI  - [Mathematical model of the age-related changes in peripheral T cells population].
AB  - An analysis is presented of the data concerning to the decline with the age the
      human immune system function. The most prominent changes links with T-cellular
      immunity. The embrace the naive T cells generation rate diminishing, peripheral
      lymphoid tissue volume shrinkage, absolute and relative concentration of naive T
      cells in blood decreasing, average length of T cell telomers reducing. The
      alterations in immune system led to sharp growth of morbidity and mortality
      caused by infectious agents. Analysis of the data reveal that key variables of
      this process are memory and naive T cell concentrations in peripheral lymphoid
      tissue. The proposed long-time mechanism which hold concentration of T cells in
      physiological limits are based on assumptions that naive and memory T cells
      disposed in common niche. The average life-time of memory T cells are varied so
      that general concentration of T cells holds in normal limits. Numerical
      experiments demonstrate that average life-time of memory T cells grows with
      aging, limitation of antigenic load led to considerable grow of resistance in
      middle age but to little grow in older age. Restriction of thymus involution led
      to grow of resistance in older age but compensate by diminishing of memory power
      and longevity. CONCLUSION: The proposal model describe the trade-off between
      naive and memory T cell subpopulations concentrations and proliferative
      potentials.

PMID- 11582755
TI  - [Thymus and aging].
AB  - This review is devoted to the analysis of current knowledge on the structure
      functional organization of thymus, its role in homeostasis regulation and in
      mechanisms of ageing.

PMID- 11582757
TI  - [Strategic directions of the international association of gerontology].

PMID- 11582758
TI  - [Mathematical and simulating model of accelerated aging induced by 5-bromo-2
      deoxyuridine].
AB  - The principles of stochastic modeling and simulation of the processes of aging
      and carcinogenesis by means of semimartingale methods are considered. The model
      fits to the experiments on activating of processes of aging be 5
      bromodeoxiuridine postnatal exposure inducing genome instability. The model
      describes the multistage phenomena of aging and carcinogenesis by the system of
      stochastic equations in terms of multivariate and diffusion processes.

PMID- 11582759
TI  - [Psychophysiological mechanisms of the vitauct].
AB  - Psychophysiological mechanisms of vitaukt in human information processing were
      studied. 90 women and 60 men and in four age groups: 20-29, 30-39, 40-49 and 50
      60 were examined. The information processing was studied by three computer's
      tests with difference complexity. The time and accuracy of each assignment were
      registered for each tests. The psychophysiological organization as characteristic
      of human functional system was studied by entropy. The results are showed
      increase of determinism of psychophysiological organization with simplification
      of informational processing. Aging weakening of psychophysiological organization
      determinism reflects in the increasing of informational processing protraction.
      The psychophysiological mechanism of vitaukt relation with increases the
      stochastic of informational processing system in aging involution condition.

PMID- 11582760
TI  - [Experience of studies of longevity phenomenon in Tiumen'. Health status of long
      livers: influence of hereditary, ecological, climatic and social factors on life
      span].
AB  - Aging of population in Tyumen region and a growing number of long livers, marked
      in last decade, make research of medical and social aspects of this age persons
      actual. Complex examination of 84 persons (age 90-102 years) was made. High
      longevity of parents, absence of chronic internal diseases complications in them,
      mechanisms of adaptation to severe climatic conditions due to the long living in
      Tyumen region are important factors for determination of longevity phenomenon.

PMID- 11582761
TI  - [A low-calories diet as a model of life span expansion and study of mechanisms of
      aging].
AB  - The model of experimental augmentation of life expectancy animal with the help of
      a low-calorie diet designed empirically more 50-[symbol: see text] of years back.
      The translation animal on such diet is accompanied by development of stress-
      response and the further adaptation to restricted power supply. As a result of it
      occurs complex change in all metabolic systems of an organism (energy system of a
      cell, endocrine, immune system, system of toxicity release, connecting tissue,
      activity genetic and system which synthesizes an protein). The orientation of
      these changes provides retardation of development, delay of formation age
      dependent of pathologies, and as the consequence, augmentation average life and,
      that is especially important, maximal life expectancy. The effect of augmentation
      of life expectancy at use of low-calorie diets depends on quantitative
      restriction of a calorific within the framework of 40-75%, sex and genotype
      animal, age animal at the moment of translation on a diet. The proposition
      expresses, that the prolongation of life at use to a low-calorie diet can be
      surveyed as specific response of some organisms in a population (not everything,
      the part animal perishes in a start of experiment) on such stressful action as
      restriction of nutrition.

PMID- 11582762
TI  - [The aging of the brain: relationship of difference between left and right
      cerebral hemisphere potential and motor asymmetry of mice].
AB  - Difference between left and right cerebral hemisphere potential (mV) is
      biophysical reflection of brain asymmetry. Cymbate changes of constant potential
      run during the life in both hemisphere of brain of mice. Number turning on the
      right of 10 attempt in T maze is a quantitative criteria of functional motor
      asymmetry. Manifest right asymmetry of behavior of mice observe only from 12 to
      17 month old. Ambylateral behavior is character to animals younger and older this
      period. Thus, as difference between left and right cerebral hemisphere potential
      both motor asymmetry have nonlinear change with age. Coefficient of correlation
      between this parameters equal -0.42 for young (3-7 month) mice, +0.53 for old (21
      28 month) mice. But this coefficient is near zero for mice from 11 to 19 month
      old. Results of our research show, that quality change in brain run in middle
      age.

PMID- 11582763
TI  - [Current trends of social gerontology].
AB  - The urgent need of understanding of social consequences of a population aging are
      discussed in the paper. It was stressed that an existence and wellbeing of the
      elderly depend not only on the financial resources of an society but also
      oninterrelations between various social groups. An historical aspects of
      relations of a society at whole as well as medical workers to the problems of the
      elderly are discussed as well.

PMID- 11582764
TI  - [Demographic forecasts for Russia and Ukraine].
AB  - The paper aim is making a comparative analysis of demographic forecasts for
      Russia and Ukraine till the 30-th of the 21-st century published in the last
      decade. More than ten forecasts made by different scientific centres and
      demographers have been considered, each of them in turn consisting of several
      variants. Some authors' projections have been also included.

PMID- 11582765
TI  - [History of social services in Russia].
AB  - The paper have deal with the historical aspects of establishment and development
      of a social works in Russia. The brief information on normative and legislative
      bases in the field of medico-social care on a population, on professional
      background, education and functional requirement are given as well.

PMID- 11582766
TI  - [Thermodynamic theory of aging explaining reasons of aging and death with
      standpoint of general laws of nature].
AB  - Thermodynamic theory of aging explains changes of the functions of states of
      cells and tissues during aging. The rates of aging depend on the genetic factors,
      the nature of habitat, nutrition and external influences. These rates can be
      different. Aging of organs, functional systems and tissues, as theirs diseases,
      lead decrease of adaptational ability of organism and its death.

PMID- 11582767
TI  - Influence of environment on the mortality pattern of potentially non-senescent
      organisms. General approach and comparison with real populations.
AB  - There are no fundamental biological reasons why a living organism has to age.
      Several examples of non-senescent organisms can be found among primitive animals.
      However these organisms age when they are not in optimal environmental
      conditions. It is reasonable to suppose that the same simple reason for this may
      also be the basic cause of senescence in human beings and some other complex
      organisms with a life history that incorporates repeated reproduction. Firstly,
      the somatic stem cells of mammals exhibit the properties of potentially non
      senescent systems. Secondly, the Strehler-Mildvan correlation between the
      parameters of mortality statistics for people living in different
      countries/conditions is exactly the same as the mortality pattern for
      hypothetical populations of potentially non-senescent organisms, which do,
      however, experience senescence as a result of functioning in living conditions
      that to varying degrees prevent the total self-maintenance of the organisms.

PMID- 11582768
TI  - [How mechanisms of senile involution could appear].
AB  - Destruction of vitally important organs in primitive Invertebrates ensures
      asexual reproduction and adaptation to the environment deterioration. In course
      of morphophysiological progress reversibility of destructive processes was lost
      and their meaning has changed. One of them began perhaps to cause death from old
      age.

PMID- 11582770
TI  - [Molecular physiology of aging].
AB  - The article is dedicated to the analysis of the peptide bioregulators role in
      molecular mechanisms of ageing and age-related pathology development. There has
      been put forward the concept of peptide regulation of ageing based on the
      priority data of authors long-term investigations on inhibition of involution
      processes in organs and tissues developed with age and restoration of specific
      proteins synthesis in cells under the influence of natural and synthetic peptide
      bioregulators. The prospects of peptide bioregulators employment in
      gerontological practice are being discussed in the paper with the purpose of
      treatment and prevention of age-associated pathology and human longevity
      increase.

PMID- 11582769
TI  - [Mathematical modeling and simulation of life history and tradeoffs].
AB  - General trends in mathematical life history modeling are reviewed. In modern
      experimental biogerontology life history consists of all traits that affect
      fecundity and survival. Tradeoffs are of special importance in the theory of life
      history, studied either as an evolutionary phenomenon or as a feature of
      individual life history. Tradeoffs between cost of reproduction and survival are
      mostly studied and modeled. Special attention is given in the review to
      statistical modeling of life history (Monte-Carlo techniques). A number of
      modeling paradigms is presented and their perspectives are discussed.

PMID- 11582771
TI  - [The use of mutagenic and transgenic mice for the study of aging mechanisms and
      age pathology].
AB  - Increased interest is emerging for using mouse models to assess the genetics of
      aging and age-related diseases, cancer including. Despite this demand, relatively
      little information is available on relations between aging and spontaneous tumor
      development in transgenic and null mutant mice. Analysis of various transgenic
      and knockout rodent models which characterized by shortening or extension of the
      life span gives an unique possibility to evaluate the role of involved in aging
      genes in mechanisms of carcinogenesis. Only few models represent examples of life
      span extension. Ames dwarf mutant mice, p66-/- knocked out mice, aMUPA and MGMT,
      transgenic mice live longer than wild-type strains. The incidence of spontaneous
      tumors in these mice was usually similar to those in controls, whereas the latent
      period of tumor development was increased. Practically all models of accelerated
      aging show the increased tumor incidence and shortening of tumor latency. This
      phenomenon has been observed both in animals which display phenotype more
      resemble to the natural aging and in animals showed only partial features of
      normal aging process. These observations are in agreement with the data on the
      positive correlation between tumor incidence and the rate of its age-related
      increase, and the aging rate in a population.

PMID- 11582772
TI  - [The natural history of telomeres].
AB  - Telomeres are end chromosome structures, which may shorten because of DNA end
      replication problem and non-reparability of free-radical damage to telomeric DNA.
      Telomerase is an enzyme serving to maintain telomere length at a species-specific
      level. The absence of telomerase in somatic cells is widely believed to be the
      cause of the limited proliferative potential of somatic cells achieved when
      telomere length, which diminishes over successive cell generations, becomes
      critically short. However, telomeres are known to be highly heterogenous with
      regard to their length even in cloned cell populations. In this review data on
      telomer length distribution and changes in characteristics of these distributions
      observed over time are considered along with hypotheses about the nature of these
      phenomena. The following conclusions are drawn: causes of the known features of
      telomere length distribution are not limited to mere scattering and measurement
      error, and so any concepts concerning the relationships between telomere length
      and cell fate should take characteristics of telomere heterogeneity in
      consideration; the ratio of the initial telomere length and the rate of telomere
      shortening does not determine the proliferative potential of non-transformed cell
      populations and does not limit the lifespans of multicellular organisms;
      telomerase functions in non-germinal cells are either unnecessary or unknown;
      telomere heterogeneity may result from the stochastic nature of events committing
      cells to terminal differentiation and/or the loss of cell capacity to
      proliferate.

PMID- 11582773
TI  - Gel renaturation assay for ribonucleases.

PMID- 11582774
TI  - Analysis of ribonucleases following gel electrophoresis.

PMID- 11582775
TI  - Ribonuclease assays utilizing toluidine blue indicator plates, methylene blue, or
      fluorescence correlation spectroscopy.

PMID- 11582776
TI  - Ribonuclease activities of trypanosome RNA editing complex directed to cleave
      specifically at a chosen site.

PMID- 11582777
TI  - Ribonuclease YI*, RNA structure studies, and variable single-strand specificities
      of RNases.

PMID- 11582778
TI  - Bovine pancreatic ribonuclease A: oxidative and conformational folding studies.

PMID- 11582779
TI  - Purification of engineered human pancreatic ribonuclease.

PMID- 11582780
TI  - Degradation of double-stranded RNA by mammalian pancreatic-type ribonucleases.

PMID- 11582781
TI  - Seminal ribonuclease: preparation of natural and recombinant enzyme, quaternary
      isoforms, isoenzymes, monomeric forms; assay for selective cytotoxicity of the
      enzyme.

PMID- 11582782
TI  - Angiogenin.

PMID- 11582783
TI  - Eosinophil-derived neurotoxin.

PMID- 11582784
TI  - The ribonuclease T1 family.

PMID- 11582785
TI  - Eosinophil cationic protein.

PMID- 11582786
TI  - A natural classification of ribonucleases.

PMID- 11582787
TI  - Deciphering the mechanism of RNase T1.

PMID- 11582789
TI  - RNase U2 and alpha-sarcin: a study of relationships.

PMID- 11582788
TI  - Mitogillin and related fungal ribotoxins.

PMID- 11582790
TI  - Secretory acid ribonucleases from tomato, Lycopersicon esculentum Mill.

PMID- 11582791
TI  - Leczyme.

PMID- 11582792
TI  - Prokaryotic type 2 RNases H.

PMID- 11582793
TI  - RNase H1 of Saccharomyces cerevisiae: methods and nomenclature.

PMID- 11582794
TI  - Ribonucleases H of the budding yeast, Saccharomyces cerevisiae.

PMID- 11582795
TI  - Ribonuclease T2.

PMID- 11582796
TI  - Human RNases H.

PMID- 11582797
TI  - Assays for retroviral RNase H.

PMID- 11582798
TI  - Sequence-selective artificial ribonucleases.

PMID- 11582799
TI  - RNA cleavage by 1,4-diazabicyclo[2.2.2]octane-imidazole conjugates.

PMID- 11582800
TI  - Preparation and use of ZFY-6 zinc finger ribonuclease.

PMID- 11582801
TI  - RNA cleavage by the 10-23 DNA enzyme.

PMID- 11582802
TI  - Leadzyme.

PMID- 11582803
TI  - Hammerhead ribozyme structure and function in plant RNA replication.

PMID- 11582804
TI  - Kinetic analysis of bimolecular hepatitis delta ribozyme.

PMID- 11582806
TI  - Catalytic and structural assays for the hairpin ribozyme.

PMID- 11582805
TI  - The ribonuclease P family.

PMID- 11582807
TI  - Intracellular applications of ribozymes.

PMID- 11582808
TI  - Barnase-barstar interaction.

PMID- 11582809
TI  - Cytoplasmic ribonuclease inhibitor.

PMID- 11582810
TI  - Small molecule inhibitors of RNase A and related enzymes.

PMID- 11582811
TI  - Ribonuclease-resistant RNA controls and standards.

PMID- 11582812
TI  - Nonenzymatic cleavage of oligoribonucleotides.

PMID- 11582813
TI  - Fast, facile, hypersensitive assays for ribonucleolytic activity.

PMID- 11582814
TI  - Activity staining for detection of ribonucleases using dried agarose film overlay
      method after isoelectric focusing.

PMID- 11582815
TI  - JCAHO issues requirements for hospitals to assess their staffing effectiveness.

PMID- 11582816
TI  - Medical gas mix-ups.

PMID- 11582817
TI  - Supervising graduate medical students in the hospital.

PMID- 11582818
TI  - Clarifying patient care standards in ambulatory care.

PMID- 11582819
TI  - Conduct disorder: a challenge to child psychiatry.

PMID- 11582820
TI  - Effective interventions for children and adolescents with conduct disorder.
AB  - Many different types of interventions have been used to treat children and
      adolescents with conduct disorder (CD). Unfortunately, most have had very limited
      effectiveness and, in some cases, have even shown iatrogenic effects. A primary
      reason for this limited effectiveness has been the failure of most treatments to
      directly address the causal mechanisms implicated in the development of CD. A few
      exceptions that have based interventions on the available research and that have
      proven to have some efficacy in reducing the conduct problems in youths with CD
      are reviewed. More important, a model for intervention is presented. This model
      emphasizes that interventions for youths with CD need to be comprehensive. That
      is, they need to take into account the myriad factors both within the child and
      within his or her social context that can cause and maintain CD symptoms.
      Further, interventions need to be individualized; they need to take into account
      the different pathways along which children may develop CD. Two intervention
      approaches that are consistent with these principles are reviewed, as are
      important directions for advancing treatment technology for youths with this
      disorder.

PMID- 11582821
TI  - Conduct disorder: a biopsychosocial review.
AB  - OBJECTIVE: To review published works on the epidemiology, risk factors,
      protective factors, typologies, and genetic aspects of conduct disorder (CD).
      METHOD: Findings from refereed journal articles and current texts in the field
      are briefly summarized. RESULTS: CD is commonly encountered in clinical practice.
      Factors strongly predictive of future delinquency include past offenses,
      antisocial peers, impoverished social ties, early substance use, male sex, and
      antisocial parents. Factors that moderately predict recidivism include early
      aggression, low socioeconomic status (SES), psychological variables such as risk
      taking and impulsivity, poor parent-child relationships, poor academic
      performance, early medical insult, and neuropsychological variables such as poor
      verbal IQ. Mildly predictive variables include other family characteristics such
      as large family size, family stress, discord, broken home, and abusive parenting,
      particularly neglect. Protective factors include individual factors such as skill
      competence (in social and other arenas), adult relationships, prosocial and
      proeducational values, and strong social programs and supports. CONCLUSIONS: We
      know a great deal about psychosocial risk factors for CD. Some research into
      protective factors and genetic contributions exists but is in its early stages.
      Future work will increase our knowledge about subtypes, developmental pathways,
      and CD treatment.

PMID- 11582822
TI  - Physical and sexual abuse issues among youths with substance use problems.
AB  - OBJECTIVES: To evaluate the prevalence of reported physical and sexual abuse
      among youths with substance use problems, to explore whether youths report
      relying on substances to cope with the abuse, and to examine whether individual
      factors related to substance use were associated with the outcome measures of
      reported physical abuse, sexual abuse, and using substances to cope. METHOD: We
      assessed 287 male and female youths (age 14 to 24 years) who presented for help
      for substance use problems, using a semistructured interview that focused on
      substance use, history of previous sexual and physical abuse, and coping
      strategies. RESULTS: One-half of the female youth substance abusers reported
      having been sexually abused (50.0%), while male youth substance users reported a
      significantly lower rate (10.4%). Similarly, one-half of the female youths had a
      history of physical abuse (50.5%), and males again had a lower rate (26.0%). Of
      those who endorsed a history of abuse, more females (64.7%) than males (37.9%)
      reported using substances to cope with the trauma. Specific associations between
      the outcome measures and substance use variables were found for youths in both
      sexes. CONCLUSION: These findings underscore the importance of why clinicians
      should explore abuse issues with substance-using youth of both sexes. Identifying
      concurrent factors will help provide better intervention strategies. Suggestions
      for assessing sexual and physical abuse in youths with substance use disorders
      are provided.

PMID- 11582823
TI  - Supportive-expressive group psychotherapy for persons with inflammatory bowel
      disease.
AB  - OBJECTIVE: Supportive-expressive (SE) group psychotherapy is designed to be
      applicable to medically ill populations. In this open trial, SE therapy was
      adapted for use in treating inflammatory bowel disease (IBD). METHOD: Thirty
      subjects with Crohn's disease (CD) or ulcerative colitis (UC) were enrolled in 4
      psychotherapy groups. Each group met weekly for 20 weeks to discuss emotional and
      interpersonal issues associated with illness. Physical and psychological
      variables were measured at the onset and at the finish of the group sessions.
      RESULTS: There was no mean group change in quality of life (QL), anxiety, or
      depression over the course of treatment, although there was a mean group
      reduction in maladaptive coping. CONCLUSION: Although the trial was uncontrolled
      and the sample size small, which limits interpretation, the results are
      consistent with an ineffective intervention. Because a null result would be
      consistent with previously reported psychotherapeutic trials in cases of IBD, and
      because SE therapy has been effective in treating other medically ill
      populations, we discuss characteristics of IBD that may account for a relative
      resistance to psychotherapeutic support.

PMID- 11582824
TI  - Attachment disorganization and dissociative symptoms in clinically treated
      adolescents.
AB  - OBJECTIVE: To examine the association of unresolved and unclassifiable attachment
      with dissociative symptomatology in a sample of 133 adolescents in psychiatric
      treatment. METHOD: The study compared 69 adolescents who were unresolved and
      unclassifiable with 64 adolescents who were not unresolved and unclassifiable.
      Attachment organization was assessed using the Adult Attachment Interview (AAI).
      Dissociative symptomatology was assessed using a scale derived from the Youth
      Self Report (YSR) behaviour checklist. RESULTS: A continuing unresolved and
      unclassifiable response to attachment-related trauma was correlated with
      dissociative symptomatology for both male and female adolescents. CONCLUSIONS:
      Cognitive disorganization may be an important variable mediating between the
      effects of earlier traumatic caregiving experiences and later dissociative
      symptoms.

PMID- 11582825
TI  - Alcohol consumption and major depression: findings from a follow-up study.
AB  - OBJECTIVE: To investigate whether alcohol consumption predicts major depressive
      disorder episodes (MDEs) in the general population. METHOD: The respondents
      without depression (n = 12,290) in the longitudinal cohort of the Canadian
      National Population Health Survey (NPHS) were classified into cohorts based on
      any drinking, frequency of drinking, maximum number of drinks on a maximal
      drinking occasion, and average daily alcohol consumption, based on data collected
      in the 1994-1995 survey. Major depression frequency 2 years later, in 1996-1997,
      was evaluated and compared across drinking categories. RESULTS: The respondents
      who reported any drinking, drinking daily, having more than 5 drinks on a maximal
      drinking occasion, and having more than 1 drink daily on average, did not have an
      elevated risk of major depression. A trend in the data suggested that women who
      reported having more than 5 drinks on a maximal drinking occasion might be at a
      higher risk of major depression. No evidence of confounding or effect
      modification by demographic, psychological, and clinical variables was found.
      CONCLUSION: In a general population sample, alcohol consumption levels were not
      associated with major depression. Having more than 5 drinks on a maximal drinking
      occasion, however, may be associated with an increased risk of major depression
      among women. Extreme patterns of alcohol consumption, which tend to characterize
      clinical samples, are associated with depression. These patterns of drinking,
      however, are relatively uncommon in the general population, and the current
      analysis may have lacked power to detect these associations.

PMID- 11582826
TI  - [The French concept of "Athymhormie" (Loss of vital force) from 1922 to the
      present].
AB  - The psychiatric concept of athymhormie (loss of vital force "elan vital" and
      affectivity) was developed at the beginning of the 20th century and used
      exclusively in France, until it was fortunately adopted by mostly French-speaking
      neurologists. The authors of the concept, M Dide and P Guiraud, considered the
      term an independent entity, an heir to dementia praecox, for which they did not
      like to substitute a "schizophrenia" with blurry boundaries. This term then came
      to mean to them, and to most French psychiatrists to this day, the basic core of
      psychosis' deficient forms. The word athymhormie (or loss of psychic self
      activation) is now also used in neurology for the behavioural and emotional
      consequences of lesions caused on basal nuclei and, more widely, of a circuit
      associated with the limbic loop. However, the phenomenological reality of the
      associated disorders and the relevance of the same name can be questioned. This
      review concludes that although the settings--in a psychiatric or a neurologic
      clinic--where athymhormie takes place are very different, the choice of the same
      name is justified in a renewed and symptomatic neuropsychiatric approach. The
      objective of this approach is to explore why some symptoms, common or similar,
      could represent the lack of a physiological function, presumed here to be
      motivation.

PMID- 11582827
TI  - Treating psychosis: is there more to early intervention than intervening early?
AB  - While the possibility of early intervention following the initial onset of
      psychotic disorders such as schizophrenia is an exciting development, a closer
      examination of the nature and content, as well as the timing, of treatment is
      required for this new approach to be successful. Modification and integration of
      diverse treatments need to be empirically investigated for their potentially
      greater effectiveness in patients who are, in general, much younger, naive to the
      mental health system, and possibly capable of full integration into society.
      Reducing delay in treatment initiation may be complex, may involve adopting early
      identification strategies, and may pose significant systemic and conceptual
      challenges. The 2 aspects of early intervention--integration of phase-specific
      treatments and early case identification--need to go hand in hand to ensure that
      another opportunity will not be missed in our efforts to improve the outcomes of
      these most serious of all mental disorders.

PMID- 11582828
TI  - Peritraumatic dissociation, acute stress, and early posttraumatic stress disorder
      in victims of general crime.
AB  - OBJECTIVE: To compare the relation between peritraumatic dissociation and acute
      stress and the early development of posttraumatic stress disorder (PTSD) in
      victims of general crime. METHOD: A total of 48 subjects were assessed within 24
      hours of the trauma, using the Peritraumatic Dissociative Experiences
      Questionnaire Self-Report Version (PDEQ-SRV). They were followed longitudinally
      to assess acute stress (2 weeks after the assault,) using the Standford Acute
      Stress Reaction Questionnaire (SASRQ), and posttraumatic stress (at 5 weeks),
      using the Clinician-Administered PTSD Scale (CAPS) and the Impact of Event Scale
      (IES). RESULTS: Among PTSD subjects mean PDEQ scores were significantly higher
      (mean 3, SD 0.9) than in those without PTSD (mean 2.3, SD 0.7) (t = 2.78, df 46,
      P = 0.007). Among PTSD subjects, mean SASRQ scores were significantly higher
      (mean 97.9, SD 29.2) than in those without PTSD (mean 54.8, SD 28.2) (t = 4.9, df
      46, P = 0.00007). CONCLUSIONS: High levels of peritraumatic dissociation and
      acute stress following violent assault are risk factors for early PTSD.
      Identifying acute reexperiencing can help the clinician identify subjects at
      highest risk.

PMID- 11582829
TI  - Moving from the clinic to the community: the alone mothers together program.

PMID- 11582830
TI  - Citalopram overdose, serotonin toxicity, or neuroleptic malignant syndrome?

PMID- 11582831
TI  - Lycanthropy: 2 case reports.

PMID- 11582833
TI  - Misleading drug advertising.

PMID- 11582832
TI  - Re: Weight change with antipsychotic use.

PMID- 11582834
TI  - Comparison of the eating and cooking habits of northern Europe and the
      Mediterranean countries in the past, present and future.
AB  - It was already possible to demonstrate in the 50s that the Mediterranean
      countries have significantly less coronary heart disease than northern Europe and
      the USA and that this correlated closely with the diets of people in the
      Mediterranean region. Consequently, the traditional Mediterranean corresponds to
      the ideas of dietetics about a preventive diet with its high percentage of fruit,
      vegetables, cereal products legumes, olive oil and its slight share of animal
      products. However, an increase of the share of animal products can be detected in
      the diet of the Mediterranean populations with increasing wealth to the detriment
      of basic foodstuffs on a vegetable basis and their positive effects. This is
      reducing the preventive effect of the diet. The dietary situation is also
      becoming worse in northern Europe, which was already found to be unfavorable in
      the 60s. The reasons for this development can be found in the substantial
      socioeconomic changes throughout all of Europe over the past 40 years. A return
      or reversal to the Mediterranean way of eating would be desirable due to its
      positive effects. But the strong trend to convenience products and eating out is
      in opposition to this.

PMID- 11582835
TI  - Guidelines for the intake of vegetables and fruit: the Mediterranean approach.
AB  - Various studies have demonstrated that the nutrient and non-nutrient substances
      present in vegetables and fruit (V&F) are most likely to be responsible for the
      beneficial effect of the increased V&F consumption. Urged by scientific evidence,
      current dietary guidelines strongly recommend the consumption of V&F in
      substantial amounts. In a recent paper (Brit. J. Nutr. 2000; 84, 549-556) V&F
      availability in 10 European countries was compared with the WHO recommendations
      (minimum combined V&F intake of about 400 g/day/person), as well as with
      guidelines of a minimum daily intake of three portions of vegetables (approx. 250
      g/person) and two portions of fruit (approx. 150 g/person). All countries,
      excluding Greece, had a vegetable intake below the recommended minimum. Moreover,
      in all countries, the percentages of low vegetable consumers were significantly
      higher than those of low fruit consumers, suggesting that there is considerable
      room for improvement in the intake of vegetables, an important source of
      antioxidants. Wild edible greens are among the vegetables commonly consumed in
      Greece. These greens have a high flavonoid content, which in several cases
      substantially exceeds the respective values in foods and beverages, such as
      onions, black tea and red wine (Food Chemistry 2000; 70, 319-323). The high
      flavonoid content of edible wild greens requires consideration of their role in
      contemporary diet, as a possible mean for increasing vegetable consumption.

PMID- 11582836
TI  - Mediterranean diet and lifestyle: special aspects of Spain.

PMID- 11582838
TI  - Mediterranean type of diet for the prevention of coronary heart disease. A global
      perspective from the seven countries study to the most recent dietary trials.

PMID- 11582837
TI  - Mediterranean diet and life style: comparison with Japanese and other eastern
      diets.

PMID- 11582839
TI  - Homocysteine, folate, and cardiovascular disease.
AB  - Cardiovascular disease (CVD) continues to be one of the main causes of mortality
      in the western world, however approximately only two-thirds of all episodes can
      be attributed to traditional environmental and genetic risk factors. Over the
      past decade it has emerged that a moderate elevation in plasma concentrations of
      the amino acid homocysteine (tHcy) constitutes a risk factor for atherosclerotic
      vascular disease in the coronary, cerebral and peripheral vessels. Furthermore,
      this association is a graded one with no apparent threshold and is independent
      of, but may enhance the effect of conventional risk factors. Plasma homocysteine
      is determined by both genetic and nutritional factors. The B-vitamins folate, B
      12 and B-6 all play a key role in homocysteine metabolism and in fact it has been
      proposed that about two-thirds of all cases of hyperhomocysteinemia are due to an
      inadequate status of one or all of these vitamins. Of the three, folate appears
      to be the most important determinant and has been shown to significantly lower
      homocysteine concentration when administered at doses ranging from 0.2 to 10 mg/d
      in both healthy and hyperhomocysteinemia subjects. There is considerable
      variation in the rate of CVD mortality between northern and southern European
      countries. A common dietary element in regions with lower CVD incidence i.e.
      southern European countries appears to be the higher consumption of fruit and
      vegetables. In the past this protective effect of fruit and vegetables has been
      primarily attributed to antioxidants. Fruit and vegetables are however also one
      of the main sources of folate in the diet, contributing to more than 30% of total
      dietary folate intake (even in countries where consumption of fruit and
      vegetables is low). Thus, in light of the evidence that folate may play a role in
      primary prevention of CVD via homocysteine-lowering the protective effect of
      fruit and vegetables may be partly explained by folate.

PMID- 11582840
TI  - Olive oil and the Mediterranean diet.
AB  - The high intake of olive oil in the Mediterranean diet contributes to the low
      intake of saturated fatty acids among populations in Southern Europe and is
      associated with a low incidence of coronary heart disease. Replacement of
      saturated fatty acids with oleic acid leads to a reduction in low-density
      lipoprotein (LDL) cholesterol without decreasing the concentration of high
      density lipoprotein (HDL) cholesterol. Oleic acid, however, may not be neutral
      with regards to its effects on risk of thrombosis which may have adverse
      consequences in populations with established atherosclerosis.

PMID- 11582841
TI  - Antioxidant properties of Mediterranean diet.

PMID- 11582842
TI  - Influence of Mediterranean diet and Mediterranean lifestyle on calcium and bone
      metabolism.

PMID- 11582843
TI  - Role of fiber in Mediterranean diet.

PMID- 11582844
TI  - Alcohol in the Mediterranean diet: benefits and risks.

PMID- 11582845
TI  - Towards a structuralist understanding of gender differences in health.

PMID- 11582846
TI  - [From women's health to gender-sensitive health research].

PMID- 11582847
TI  - Gender differences in health-related behaviours: the BRFSS experience.

PMID- 11582848
TI  - Snow and Farr: a scientific duet.

PMID- 11582849
TI  - The changing assessments of John Snow's and William Farr's cholera studies.
AB  - This article describes the epidemiological studies of cholera by two major
      British investigators of the mid-nineteenth century, John Snow and William Farr,
      and it asks why the assessments of their results by contemporaries was the
      reverse of our assessment today. In the 1840s and 1850s Farr's work was
      considered definitive, while Snow's was regarded as ingenious but flawed.
      Although Snow's conclusions ran contrary to the exceptations of his
      contemporaries, the major reservations about his cholera studies concerned his
      bold use of analogy, his thoroughgoing reductionism, and his willingness to
      ignore what seemed to be contrary evidence. Farr's electric use of current
      theories, his reliance multiple causation, and his discovery of a mathematical
      law to describe the outbreak in London in 1849 was much more convincing to his
      contemporaries. A major change in thinking about disease causation was needed
      before Snow's work could be widely accepted. William Farr's later studies
      contributed to that acceptance.

PMID- 11582850
TI  - Beyond biology: the social context of prenatal behaviour and birth outcomes.
AB  - OBJECTIVES: In this study we examine the factors that are associated with adverse
      birth outcomes using a representative national sample. In our analysis we take
      into account factors which are related to the mother's behaviour during pregnancy
      and also consider the socio-economic circumstances of the family. METHODS: A
      series of logistic regression models are used to determine the increased risks of
      low birth weight, preterm, and small for gestational age births associated with
      maternal smoking, alcohol consumption and high blood pressure in relation to
      socio-economic factors, such as family dysfunction, social support, income
      adequacy, age, and education. RESULTS: All socio-economic factors showed
      gradients of maternal smoking during pregnancy while only mother's education and
      socio-economic status demonstrated gradients of alcohol use and high blood
      pressure. Maternal smoking, high blood pressure, higher levels of family
      dysfunction, and lower levels of mother's education were found to significantly
      increase the risk of an adverse birth outcome. CONCLUSIONS: Interventions
      designed to mitigate the hazards of adverse birth outcomes should be designed to
      reflect the gradients of risky prenatal maternal behaviours associated with age,
      education, income, and family dysfunction.

PMID- 11582851
TI  - [Men and health--new epidemiological data from Germany in a summary].
AB  - OBJECTIVES: In epidemiological investigations men are often considered and used
      as the healthy control group. This article aims to provide a detailed overview
      about health in men. METHODS: Analyses of the indices of health (life expectancy;
      mortality; state of health) and health-related behaviour (drinking, smoking, and
      eating behaviour; use of the health system' services) were performed, using data
      of the German Health Board (1999) and of an health survey in commission of the
      state (1998) plus data from our own representative investigations of 1994 and
      1996. RESULTS: Men, in comparison to women, have a shorter life expectancy as
      well as a higher mortality rate when suffering from cardiac infarction, lung
      cancer, traffic accidents, or suicide. In consideration of health-related
      behaviour, men do smoke and drink more and more frequently than females. In
      addition, men call on the services of the health system to a lesser extent and
      deny psychological influences to their health. Effects of age and differences
      between East and West Germany were obtained. CONCLUSIONS: The presented data can
      only be explained by a combination of biological, psychological, and sociological
      perspectives. According to these results, investigations of health-related data
      should focus more on the difference between men, on the gender-related role of
      men in different contexts and on the investigation of the sub-group of healthy
      men.

PMID- 11582852
TI  - [Regional and sex-specific differences in fulfillment of patient rights: results
      of a representative population survey in Munich, Dresden, Vienna and Bern].
AB  - OBJECTIVES: The European Office of the World Health Organization formulated the
      Amsterdam Declaration in 1994, demanding thereby the realisation of the
      principles of a humane health care. These principles relate to the protection of
      dignity of personhood, to self-determination, the right of information, and the
      right of quality, continuity and equality in health care. The present study aims
      at a gender-specific analysis of the fulfillment of these rights. METHODS:
      Computer-assisted telephone interviews were conducted during the months February
      and March 2000 in four German speaking European cities (Munich, Dresden, Vienna
      and Berne). A paragraph of the Declaration on the Promotion of Patients' Rights
      was regarded as fulfilled if there was at least 80% agreement. RESULTS:
      Deficiencies were most pronounced for the provision of community and domiciliary
      services after hospital treatment and for the right concerning humane terminal
      care and death in dignity. Moreover, regional differences were found between
      Munich, Dresden and Vienna on one side and Berne on the other side, with degrees
      of fulfillment being higher in Berne. CONCLUSIONS: In summary, these regional
      differences are more pronounced than single gender-specific differences, which
      may be due to chance. Areas with potential for improvement could be identified
      and can be actively restructured, e.g., in the context of the setting of health
      targets. An evaluation of the influence of the managed care system which has been
      established only sporadically in Berne requires more data.

PMID- 11582853
TI  - The Innsbruck Women's Health Study 1999: health status and behaviour.
AB  - OBJECTIVES: The aim of this study is to report descriptive results of a recent
      survey on women's health and to analyse associations between perceived health
      status and health behaviour. METHODS: A cross-sectional survey on 609 women aged
      20 to 95 years was performed in Innsbruck (Austria) in 1999. RESULTS: Self
      reported poor health status was 6% in the 20-39 age group, 10% in the 40-59 age
      group and 20% in the 60 and older age group. Age and physical activity were
      significant predictors for health status. Women who performed physical activities
      on a regular basis had a more than 70% reduced risk of poor health status.
      Concerning the prevalence of self-reported morbidity, urogenital disorders (35%),
      allergies (32%), and headache (42%) were most frequent in younger women whereas
      skeletal disorders such as rheumatic diseases (41%), osteoporosis (39%), and
      invertebral disc damage (39%) in older women. Important health behaviour-related
      problems to be found were 40% smoking among women under 40, and 42% overweight or
      obesity among women over 60. Stress affected 37% of women under 60 years of age.
      CONCLUSIONS: Physical activity, smoking, overweight and stress revealed to be key
      indicators for improving women's health.

PMID- 11582854
TI  - Gender bias in the assessment of physical activity in population studies.
AB  - OBJECTIVES: Despite their generally more health promoting behaviours, women are
      found to participate less in physical activity than men. This study explores
      possible gender bias in measurement of physical activity in population studies.
      METHODS: Data collected by telephone (CATI) from the Berne Lifestyle Panel in
      1996 is utilised. A representative samples of the population of the city of Berne
      comprised N = 1119 cases. Gender differences are assessed for the weekly
      frequency of three measurements of physical activities. RESULTS: An indicator of
      sport and exercise showed higher physical activity among men, while the indicator
      of habitual physical activity showed higher rates of daily walking and biking
      among women. A combined indicator of general physical activity showed no
      significant gender differences. CONCLUSIONS: The results provide empirical
      evidence on potential risk of underestimation of physical activity among women
      and of misclassification with respect to high or low risk behaviour patterns.

PMID- 11582855
TI  - Separation from children as a specific risk factor to fathers' health and
      lifestyles.
AB  - OBJECTIVES: The study was to examine whether fathers living apart from their
      children following divorce or separation ("fathers without children") differ in
      their health-related lifestyles and attitudes, and in their health status, from
      fathers in intact family settings ("fathers with children"). METHODS: Data was
      acquired by means of a self-administered questionnaire within an exploratory
      cross-sectional survey. RESULTS: Fathers without children differed in their
      lifestyle patterns, parameters of satisfaction, health, and health related
      orientations from fathers with children. Negative lifestyles could be observed in
      fathers who had a low income and saw their children only rarely. CONCLUSIONS:
      Separation from their children is a major life crisis for fathers. Subgroups
      could be identified who had significant health risks. Due to study design,
      conclusions on causation are not possible. Longitudinal studies are necessary to
      yield more detailed impact for prevention.

PMID- 11582856
TI  - The thiamine status of adult humans depends on carbohydrate intake.
AB  - Thiamine requirements for humans are generally expressed as absolute values per
      day (mg/d) or in relation to total caloric intake. Limited data are available on
      the relation between thiamine requirements and the intake of carbohydrates. This
      study was performed to investigate the influence of stepwise increases of
      carbohydrate intake on the status of thiamine in healthy volunteers under
      isocaloric conditions. During an adaptation phase of four days, the carbohydrate
      intake of twelve healthy volunteers (6 male, 6 female) was 55% of total energy
      intake. During the subsequent intervention periods, carbohydrate intake was
      increased to 65% of total energy for four days and to 75% for another four days.
      Thiamine intake, total energy intake, and physical activity were kept constant
      throughout the study. HPLC analysis was used to measure thiamine in plasma, urine
      and feces. Erythrocyte transketolase activity (ETK) was determined enzymatically.
      During the intervention periods thiamine decreased significantly (p < 0.05) in
      plasma (from 19.3 +/- 3.3 to 16.4 +/- 4.0 nmol/l) as well as in urine (from 72 +/
      56 to 58 +/- 21 mumol/mol creatinine). ETK and feces content of thiamine
      remained unchanged. An increase of dietary carbohydrate intake from 55% to 65%
      and 75%, respectively, of total caloric intake for four days per period at
      isocaloric conditions causes a decrease of plasma and urine levels of thiamine
      without affecting enzyme activities.

PMID- 11582857
TI  - The alpha-linolenic acid content of green vegetables commonly available in
      Australia.
AB  - Green vegetable consumption has long been considered to have health benefits
      mainly due to the vitamins, minerals and phytonutrients (such as vitamin C,
      folate, antioxidants etc) contained in a vegetable-rich diet. Additionally, green
      vegetables are known to contain a relatively high proportion of omega-3
      polyunsaturated fatty acids (PUFAs), primarily in the form of alpha-linolenic
      acid (18:3n-3). However, there are no data available on the fatty acid
      composition and concentration of green vegetables commonly consumed in Australia.
      The present study determined the fatty acid content of 11 green vegetables that
      are commonly available in Australia. The total fatty acid concentrations of the
      vegetables under study ranged from 44 mg/100 g wet weight in Chinese cabbage to
      372 mg/100 g in watercress. There were three PUFAs in all vegetables analyzed;
      these were 16:3n-3, 18:2n-6, and 18:3n-3 fatty acids. Sample vegetables contained
      significant quantities of 16:3n-3 and 18:3n-3, ranging from 23 to 225 mg/100 g.
      Watercress and mint contained the highest amounts of 16:3n-3 and 18:3n-3, and
      parsley had the highest amount of 18:2n-6 in both percentage composition and
      concentration. Mint had the highest concentration of 18:3n-3 with a value of 195
      mg/100 g, while watercress contained the highest concentration of 16:3n-3 at 45
      mg/100 g. All 11 green vegetables contained a high proportion of PUFAs, ranging
      from 59 to 72% of total fatty acids. The omega-3 PUFA composition ranged from 40
      to 62% of total fatty acids. Monounsaturated fatty acid composition was less than
      6% of total fatty acids. The proportion of saturated fatty acids ranged from 21%
      in watercress and mint to 32% of total fatty acids in Brussels sprouts. No
      eicosapentaenoic and docosahexaenoic acids were detected in any of the samples.
      Consumption of green vegetables could contribute to 18:3n-3 PUFA intake,
      especially for vegetarian populations.

PMID- 11582858
TI  - The antioxidant and hepatoprotective effects of zinc are related to hepatic
      cytochrome P450 depression and metallothionein induction in rats with
      experimental cirrhosis.
AB  - The aim of the present study was to investigate the time-course of changes in
      hepatic lipid peroxidation, cytochrome P450 and metallothionein concentrations,
      and superoxide dismutase and catalase activities in relation to the onset and
      development of cirrhosis in CCl4-treated rats. Further, the effects of oral zinc
      administration on these parameters were assessed. Cirrhosis was induced in 120
      rats by intraperitoneal injections of CCl4 twice weekly over 9 weeks. Controls
      were 120 additional animals. Both groups were further subdivided to receive
      either a standard diet or one supplemented with zinc. Subsets of 10 animals each
      were euthanized at weeks 1, 2, 3, 5, 7 and 9 from the start of the study. Results
      indicated that zinc administration delayed the cirrhotic process and the increase
      in lipid peroxidation. These changes, consistently maintained during the first 5
      weeks of the study, were associated with a significant decrease in the hepatic
      concentration of cytochrome P450 and an increase in the hepatic concentration of
      metallothioneins. Zinc supplementation did not produce any significant change in
      superoxide dismutase and catalase activities. These results suggest that
      cytochrome P450 and metallothioneins may play an important role in the hepato
      protective effects of zinc against lipid peroxidation in experimental cirrhosis.

PMID- 11582859
TI  - Comparison of fatty acid profile in plasma phospholipids in women from Granada
      (southern Spain) and Malmo (southern Sweden).
AB  - We conducted a first pilot study on healthy women living in two countries with
      different dietary habits, Granada in the south of Spain and Malmo in the south of
      Sweden, in order to compare their levels of plasma phospholipid fatty acids, and
      to examine the relationship between the differences in food consumption. This
      study is part of a pilot study which is nested in the European Prospective
      Investigation into Cancer and Nutrition, a multi-centre prospective cohort study
      on diet, plasma concentrations of antioxidants and fatty acids, and markers of
      oxidative stress. Thirty-nine women in Granada and thirty-eight women in Malmo,
      aged 45-50 years (all pre-menopausal) were selected among the female participants
      in the cohorts from these two countries. Individual measurements of the women's
      habitual diet were obtained by a food frequency questionnaire. 24-hour diet
      recalls were used for the standardised measurement of diet at group level. Plasma
      phospholipid fatty acid composition was determined by capillary gas
      chromatography. We found a different fatty acid profile in plasma between the two
      populations, with higher mean levels of palmitic acid (16:0), palmitoleic acid
      (16:1) (n-7), oleic acid (18:1), alpha-linolenic acid (18:3) (n-3) and
      eicosapentaenoic acid (20:5) (n-3), and lower mean levels of stearic acid (18:0)
      in Malmo compared to Granada. Women in Malmo consumed more meat, alcoholic
      beverages and sugar, and less fish and shellfish than women in Granada. We
      conclude that the fatty acid composition in plasma phospholipids is different
      between women from the two European centres. For polyunsaturated fatty acids,
      differences were observed for (n-3) fatty acids. In relation to these
      differences, we observed that specific food intakes, particularly meat and fish,
      varied between the two centres.

PMID- 11582860
TI  - Dietary vitamin E supplementation protects the rat large intestine from
      experimental inflammation.
AB  - Vitamin E, the most potent antioxidant in the lipid phase, was tested for
      antiinflammatory activity in trinitrobenzenesulfonic acid-induced rat colitis.
      Rats were fed a nonpurified diet (saline and control groups) or a vitamin E
      supplemented diet (treated group, 300 mg/kg nonpurified diet). Vitamin E
      supplementation, which resulted in increased colonic vitamin E levels, reduced
      colonic weight and damage score, prevented lipid peroxidation and diarrhea,
      reduced interleukin-1 beta levels and preserved glutathione reductase activity
      and total glutathione levels. However, it did not modify myeloperoxidase levels,
      which are indicative of neutrophil infiltration in the inflamed colon. Vitamin E
      protects the rat colon from oxidative stress associated with inflammation.

PMID- 11582861
TI  - Apparent fat digestibility in rats fed different diets is negatively correlated
      with faecal bile acid excretion.
AB  - Seventy-two rats were fed one out of 9 diets differing as to protein source and
      calcium concentration. For the individual rats apparent fat digestibility and
      faecal bile acid excretion were negatively correlated. It is suggested that a
      high solubility of bile acids in the small intestinal digesta, which is
      associated with little loss of bile acids with faeces, stimulates the process of
      fat digestion.

PMID- 11582862
TI  - Consumption of fructooligosaccharides and nitrogen excretion in cats.
AB  - In a cross-over study with adult cats the effect on nitrogen (N) excretion of a
      diet supplemented with fructooligosaccharides (FOS) was compared with a diet
      supplemented with an equal amount of fructose and glucose. FOS raised N excretion
      with faeces by 26% (P < 0.05) and non-significantly lowered N excretion with
      urine by 5%. Thus, there was a shift in N excretion from urine to faeces. The
      amount of faecal dry matter was significantly higher (by 23.3%) when FOS was
      consumed.

PMID- 11582863
TI  - [To imagine in the tropics].

PMID- 11582864
TI  - [The eumycetomas (fungal mycetomas with black or white grains)].

PMID- 11582865
TI  - [Primaquine].

PMID- 11582866
TI  - [Mucocutaneous manifestations after travel in the tropics].

PMID- 11582867
TI  - [The Niakhar study zone in Senegal].

PMID- 11582868
TI  - [Meningitis epidemics: a foreseen disaster].

PMID- 11582869
TI  - [Prevalence of HIV and HBs antigen in blood donors. Residual risk of
      contamination in blood recipients in East Kinshasa, Democratic Republic of the
      Congo].
AB  - Between January and August 1999, a total of 7277 blood donors at various health
      centers in Kinshasa, Democratic Republic of the Congo were screened for human
      immunodeficiency virus 1 (HIV1) and hepatitis B surface antigen (HbsAg) using the
      ELISA technique. Findings showed an incidence of 6.4% for HIV1 antibodies, 9.2%
      for HbsAg, and 1% for HIV1 and HbsAg. Young females (under 39 years of age) from
      lower socio-economic classes were the most likely to be infected by HIV1. The
      risk of HIV transmission by transfusion of contaminated blood was 3%, which is
      close to the incidence of HIV in the general population. The findings of this
      study document the need to speed up implementation of blood donor screening in
      the city of Kinshasa and the rest of the country.

PMID- 11582871
TI  - [Prevalence of dental caries in school milieu in the northwest of Cote d'Ivoire].
AB  - The purpose of this study was to determine the prevalence of tooth decay and its
      correlation with dental care habits in northwestern Ivory Coast. Study was
      carried out in primary schools in the city of Odienne in January 1999. The study
      cohort comprised 500 students of both genders ranging in age from 4 to 15 years.
      The prevalence of tooth decay was 77.2% and the mean CAO index was 2.43. Dental
      care involved use of a chewing stick in 49% and a tooth brush in 50.8%. Only 5.6%
      of children cleaned their teeth three-times a day on a regular basis. Statistical
      analysis of study data demonstrated a correlation between the frequency of tooth
      cleaning and incidence of tooth decay. The incidence of tooth decay was 60.7% in
      students that cleaned their teeth three times a day versus 78.2% in students who
      cleaned their teeth less regularly. An educational campaign has been undertaken
      to inform students of the importance of oral hygiene in maintaining healthy
      teeth. A dental examination program would be useful to provide routine check-ups.
      A group study will be needed to monitor oral hygiene in students and evaluate the
      impact of these measures on tooth decay.

PMID- 11582870
TI  - [Causes of adult acute bacterial diarrhea in an internal medicine department in
      Libreville, Gabon].
AB  - This retrospective study of patients treated between 1992 and 1996 was undertaken
      as a preliminary step to identifying the main bacterial causes of diarrheal
      disease in Libreville, Gabon. A total 371 files showing positive stool cultures
      were analyzed. From an epidemiological standpoint, data showed that the high risk
      population was young people of both sexes. The incidence of diarrhea was
      correlated with climatic conditions with an endemic-epidemic pattern
      characterized by peak activity during the rainy season. In the vast majority of
      cases, the underlying etiology was gastroenteritis due to invasive organisms. The
      most commonly identified agents were salmonellae (46.6%) and Shigellae (44.2%).
      Treatment should focus on rehydration. Fluoro-quinolones were the most commonly
      indicated drugs for antimicrobial treatment but cotrimoxazole was often useful.
      In general, the prognosis of bacterial diarrhea is favorable provided that it is
      treated early and concurrent conditions are taken into account.

PMID- 11582872
TI  - [Evaluation of the OptiMal test in the diagnosis of imported malarial outbreak].
AB  - The OptiMal test is an immuno-chromatographic dipstick test that permits
      indiscriminate detection of Plasmodium falciparum and other species of human
      malaria. The purpose of this study was to evaluate the efficacy of the test for
      diagnosis of imported malaria. A total of 244 patients with a presumptive
      diagnosis of imported malaria in France were included during the study period.
      The reference test, i.e., combined thick and thin blood films, demonstrated
      infection by Plasmodium falciparum in 58 cases, Plasmodium vivax in 12, P. ovale
      in 8 and Plasmodium malariae in 2. The OptiMal test detected only 46 of the 55
      Plasmodium falciparum cases. The sensitivity of the test for diagnosis of that
      species was 80%, its specificity was 98%, and its positive and negative
      predictive values were 95 and 93% respectively. Parsitemia studies showed poor
      test reliability for densities lower than 150/ul. Detection of other species was
      accurate in 21 out of 22. The results of this study demonstrate that the current
      version of the OptiMal test should be used with great caution for the diagnosis
      of malarial infection in hospital practice.

PMID- 11582873
TI  - [Anogenital warts in young children in hospital consultation in Lome (Togo). Role
      of transmission by sexual abuse].
AB  - The purpose of this 20-month prospective study conducted in the dermatology
      department of Lome Teaching Hospital was to determine the prevalence of sexual
      abuse in pre-adolescent children with anogenital warts. From May 1997 to December
      1998, a total of 16 cases of anogenital warts were diagnosed in children under
      the age of 12 years. Sexual abuse was discovered in 8 cases. All 8 cases involved
      girls (mean age, 6.1 +/- 1.9 years). The mode of acquisition involved self
      infection from non anogenital warts in three cases and contamination by the
      mother in three cases. In two cases the mode of acquisition could not be
      identified. The alleged abuser was a member of child's family in 3 cases, a
      household employee working at the child's home in three cases, a teacher in 1,
      and a neighbor in 1. Syphilitic tests were negative in all children. However HIV
      infection was detected and the contaminator was identified in one 10-year-old
      girl. The results of this study document the correlation between anogenital warts
      and sexual abuse. In Black Africa, the consequences of child sexual abuse, which
      is not uncommon especially in major cities, are aggravated by the high prevalence
      of HIV infection.

PMID- 11582874
TI  - [Psychological mistreatment of children with sickle cell disease in Cameroon:
      description and analysis of 1 case].
AB  - Psychological maltreatment of a children with sickle-cell disease is a form of
      parental dysfunction provoked by a crisis situation. In most cases, this type of
      child abuse involves a relatively harmonious family going through a period of
      adaptation that jeopardizes its internal equilibrium. The weakest components of
      the family, i.e., the children, become the scapegoats for the crisis. After a
      brief description of this disorder, the authors analyze the different causes that
      lead to eruption of intra-familial violence. Several cultural, social, and
      economic factors combine to trigger the maltreatment to which hapless children
      with sickle-cell disease fall victim. Special legislation to provide appropriate
      child care is the only alternative to prevent these situations from becoming
      chronic subject only to the socio-economic conditions of the parents and
      prevailing ethos.

PMID- 11582875
TI  - [A classical form of actinomycoses involving the mouth, face bones, orbit and
      base of the cranium in an African patient].
AB  - Osteitis due to actinomycosis is now an uncommon clinical entity in
      industrialized countries. This report describes a classic case of imported
      actinomycosis involving the buccal cavity, facial bones, orbit and skull base.
      For two years after the onset, various diagnoses followed by different medical as
      well as surgical treatments were unsuccessfully attempted first in Senegal then
      in Italy. Proper diagnosis was finally established in Marseille, France, on the
      basis of histological findings after extensive surgical biopsy. The patient was
      treated with high-dose intravenous penicillin G for four weeks followed by daily
      oral administration of amoxicillin for one year. Surgical reconstruction could
      not be carried out before the patient's return to Senegal. The pitfalls of
      diagnosis and treatment of actinomycosis are discussed.

PMID- 11582876
TI  - [Cutaneous manifestations of the leukemia-lymphoma of HTLV 1: apropos of 1 case].
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus implicated in
      adult T-cell leukemia/lymphoma characterized by proliferation of infected mature
      auxiliary T-cell lymphocytes. Cutaneous manifestations of T-cell
      leukemia/lymphoma are inconsistent and variable findings. In some patients, skin
      lesions are the presenting symptoms that lead to diagnosis and in others they are
      secondary occurrences. This report describes a case of T-cell leukemia/lymphoma
      associated with serologically documented HTLV-1 infection in a 27-year-old black
      man from Surinam. Manifestations were low-grade at the time of diagnosis and
      became tumor-like at the end stage of the disease. At the time of presentation,
      examination revealed plaques of infiltrated scaly erythrematous lesions scattered
      over the entire body. One year later the patient exhibited xerodema and variable
      sized subcutaneous tumor-like nodules. This case illustrates the wide range of
      cutaneous manifestations that can be found in association with cutaneous T-cell
      lymphoma due to HTLV-1.

PMID- 11582877
TI  - [The expanded program of vaccination: 25 years tomorrow].
AB  - The expanded program on immunization will soon celebrate its 25th anniversary.
      The original program included vaccination against diphtheria, tetanus, pertussis,
      poliomyelitis, measles, and tuberculoses. It was expanded to include first yellow
      fever and hepatitis B and later haemophilus. Results are mixed. Diphtheria was
      under control but has made a major comeback since vaccination was halted in
      eastern Europe. Tetanus in newborns should no longer be a public health problem
      by 2005. Control of pertussis has not been achieved because the vaccine has been
      unsuccessful in interrupting transmission. Poliomyelitis is no longer reported in
      the Americas. Hopefully transmission of the wild virus will be stopped by 2003
      and total eradication of poliomyelitis will be achieved by 2005. For several
      reasons, there has been an alarming increase in tuberculosis with an estimated
      annual incidence of 5 million cases worldwide. Eradication of measles was
      achieved in the Americas in 2000 and is expected in the European region by 2007
      and in the east Mediterranean area by 2010. Current data on yellow fever and
      hepatitis B is inadequate, these vaccination being still poorly implemented in
      endemic areas. A more widespread use of the vaccine will be needed. However
      spending cutbacks and changing priorities in the Health Ministries will require a
      renewal of commitment to this immunization policy.

PMID- 11582878
TI  - [Co-infections of leishmania/HIV in south Europe].
AB  - The Leishmania/HIV co-infection has emerged as a result of the increasing overlap
      between leishmaniasis (mainly visceral, more rarely cutaneous) and AIDS, which is
      due to the spread of the AIDS pandemic to rural areas and that of visceral
      leishmaniasis to suburban areas. Cases of co-infection have so far been reported
      from 33 countries around the world, most of the cases have been notified in south
      western Europe. 1,627 cases have been notified from Spain, France, Italy and
      Portugal. While Leishmania/HIV co-infection is increasing in eastern Africa,
      cases of co-infection are expected to diminish in South-western Europe due to the
      new highly active anti-retroviral therapy (HAART). In 1998, a world wide
      WHO/UNAIDS surveillance network was established, which now includes 28 member
      institutions. In south-western Europe, the surveillance system based on 16
      institutions is now well established. The systematic use of standardized and
      recently computerized case-report forms, the central international registry at
      WHO headquarters, and finally the use of a geographic information system (GIS)
      for mapping and monitoring co-infections have improved the overall quality of
      epidemiological data gathering. All member institutions of the network report to
      WHO on an annual basis. World wide information is analysed and periodically
      disseminated through international publications. The GIS integrates
      epidemiological and demographic data sets and allows for the mapping of co
      infection cases down to locality level. The system can be used to easily
      visualise and analyse the spatial distribution of co-infection cases and to
      permit monitoring of the evolution of the distribution of the cases over time.
      The risk of co-infected patients, as carriers of Leishmania in the blood, to be a
      source of infection for the sandfly, has been recently confirmed. Moreover
      intravenous drug users also transmit the disease through the sharing of needles.

PMID- 11582879
TI  - [Anti-tetanus vaccination protection on the Kouilou region of Congo-Brazzaville].

PMID- 11582880
TI  - [Surveillance of pregnancy based on various documents used in prenatal
      consultation in Congo-Brazzaville].

PMID- 11582881
TI  - [Value of Quantitative Buffy Coat (QBC) in borreliasis-malaria co-infection].

PMID- 11582882
TI  - [Chagas disease in French Guiana: lack of verifiable argument in favor of a re
      emergence during the last decade].

PMID- 11582883
TI  - [Diarrhea, a problem of public health].

PMID- 11582884
TI  - [Water supply and purification in tropical environment].

PMID- 11582885
TI  - [Diarrhea and the traveler].

PMID- 11582886
TI  - [Management of acute diarrhea].

PMID- 11582887
TI  - [Management of acute diarrhea of the child in tropical environment].

PMID- 11582888
TI  - [Cholera: vaccines present and future].

PMID- 11582889
TI  - [The role of vaccines in the fight against cholera].

PMID- 11582890
TI  - [Reinforcement of national capacity for detection and response to epidemics and
      emergent illness].

PMID- 11582891
TI  - [Help Network for Ocular Health].

PMID- 11582892
TI  - [Serogroup W135 meningococcal meningitis epidemic in 2000 and 2001].

PMID- 11582894
TI  - Introduction to the special section on contemporary theoretical developments and
      the implications for group psychotherapy.

PMID- 11582893
TI  - [Vaccines against rotavirus infections].

PMID- 11582895
TI  - Group therapy and complexity theory.
AB  - Complexity theory, also called dynamical self-organizing systems theory, is a new
      scientific way of viewing the natural world. It is being applied to a vast range
      of multiply determined systems, as well as to created systems including
      psychoanalysis, and in this article to analytically informed group therapy.
      Examples of prominent features of group therapy lend themselves to comparison
      with outstanding features of complexity systems, including nonlinear determinism,
      self-organization, coevolution, and disequilibrium conditions for change and
      growth. Examples are used throughout to illustrate inferred processes called
      cascading, multisubjectivity, and asynchronous change processes. Therapist role
      indications are in the direction of implementing the group's own processes of
      creating change, at close range in the sessions.

PMID- 11582896
TI  - The postmodern turn in group therapy.
AB  - The postmodern critique, often referred to as social constructionism, has
      influenced nearly all disciplines, including recently the domain of psychology-
      and most particularly psychoanalysis. This article presents an exposition of the
      "postmodern turn," including some historical perspective, a description of its
      theoretical elements as related to psychological practice, as well as standard
      objections to its theories. This author believes that many of the concepts
      inherent to a social constructionist approach are compelling for theory and
      practice in group therapy. Clinical case studies are cited in describing how
      postmodern theories present a natural fit for group therapy. Furthermore,
      specific implications of this model are delineated for the arduous task of
      leading groups.

PMID- 11582897
TI  - The practice of Modern Group Psychotherapy: working with past trauma in the
      present.
AB  - Modern Group Psychotherapy offers specific techniques for aiding the pre-oedipal
      patient to speak, connect, and achieve emotional growth. This article illustrates
      the use of such therapeutic group tools as joining, mirroring, bridging, contact
      functioning, the object-oriented question, the insulation barrier, and transient
      identification, through case vignettes. It demonstrates how such techniques
      protect fragile egos and assist them on their journey to maturity. Emphasis is
      placed on the creative components of countertransference as a valuable supplement
      in patient treatment. The power of the group as an agent for change is portrayed.

PMID- 11582898
TI  - The group psychotherapist as contemporary mystic: a bionic object relations
      perspective.
AB  - Mysticism is a heightened awareness facilitating intuitive knowledge of group
      realities. In contrast to logical positivism, in which scientific knowledge
      consists of logic applied to a set of observations, the author holds that
      mystical awareness is pertinent to the conduct of therapy groups. The work of
      Bion, and also so-called "structuralist" theories, postulate pre-given templates
      that inform experience. The application of mystical thought to group
      consultation, leadership, and transformation of the self is discussed. The group
      context which allows for mystical experience is called the "sacred space." To
      emphasize the sacredness of the group, a kabbalist parallel to early development
      and projective identification is used to show how sacred metaphor and myth can
      enrich interpretation in groups.

PMID- 11582899
TI  - Patient personality and time-limited group psychotherapy for complicated grief.
AB  - We used a randomized clinical trial to investigate the interaction of two patient
      personality characteristics (quality of object relations [QOR] and psychological
      mindedness [PM]) with two forms of time-limited, short-term group therapy
      (interpretive and supportive) for 139 psychiatric outpatients with complicated
      grief. Findings differed depending on the outcome variable (e.g., grief symptoms,
      general symptoms) and the statistical criterion (e.g., statistical significance,
      clinical significance, magnitude of effect). Patients in both therapies improved.
      For grief symptoms, a significant interaction effect was found for QOR. High-QOR
      patients improved more in interpretive therapy and low-QOR patients improved more
      in supportive therapy. A main effect was found for PM. High-PM patients improved
      more in both therapies. For general symptoms, clinical significance favored
      interpretive therapy over supportive therapy. Clinical implications concerning
      patient-treatment matching are discussed.

PMID- 11582900
TI  - Treatment of non-incarcerated sexually compulsive/addictive offenders in an
      integrated, multimodal, and psychodynamic group therapy model.
AB  - Group therapy is a widely accepted model of care for sex offenders. However, most
      group therapy takes place in prison utilizing a cognitive-behavioral,
      psychoeducational model of care. Given that over 250,000 sex offenders are in
      ambulatory treatment, newer models of care may need to be employed to address
      their specific needs. I present a naturalistic outpatient study involving my
      private practice of 109 consecutive sex offenders treated over a 10-year period.
      A multimodal model of care informed by psychodynamic theory is presented with
      detailed case material from one group session. Preliminary results of recidivism
      are presented.

PMID- 11582901
TI  - Culture and the practice of group psychotherapy in Singapore.

PMID- 11582902
TI  - [Thenar branch of the median nerve and innervation of the trapeziometacarpal
      joint].
AB  - INTRODUCTION: Denervation has been proposed successfully for chronic wrist pain.
      This procedure is not commonly performed for degenerative osteoarthritis of the
      trapeziometacarpal joint. According to the classic anatomical descriptions of the
      wrist innervation, it seems that the thenar branch of the median nerve (TBMN) is
      the only nerve of the wrist for which no articular branches are clearly defined.
      The aim of this study is to complete the few anatomical descriptions of the
      trapeziometacarpal joint innervation with microdissections of the TBMN. MATERIALS
      AND METHODS: Ten wrist and hand specimens from fresh cadavers were dissected by
      the same operator under magnification (3.5-12x). The TBMN was identified at its
      origin from the median nerve and followed in the thenar muscles. All the
      divisions of the TBMN were identified and followed to their terminal branches.
      RESULTS: The TBMN divided in at least two main branches, one each to the opponens
      and to the abductor pollicis brevis. In all but one specimen, the branch to the
      opponens pollicis muscle passed over or into its medial aspect to spread on the
      palmar side of the trapezium. Each dissected articular branches were
      histologically confirmed. DISCUSSION: Our results show a clear participation of
      the TBMN in the innervation of the trapeziometacarpal joint. The lack of
      knowledge of this anatomical feature may explain the inconstant results obtained
      with selective denervation of the trapeziometacarpal joint.

PMID- 11582903
TI  - [Vascularized bone pedicle grafts of the hand and wrist: literature review and
      new donor sites].
AB  - Some situations in hand surgery require vascularized bone grafts. Good mechanical
      strength and decreased time for bone healing may explain their use. Although many
      donor sites have been described, the authors were interested by donor sites with
      a blood supply provided by an accessory vessel not disturbing the perfusion of
      the hand. Literature review of the different donor sites demonstrate (a) Three
      sites at the dorsal aspect of the distal epiphysis and one at the dorsal distal
      ulna. Only the radialmost site has been regularly used for surgical application.
      (b) At the palmar aspect of the radial epiphysis, the pronator quadratus
      vascularised bone graft may be elevated in an antero or retrograde way. (c) Among
      the carpal bones, the pisiform and part of the capitate has been used as
      pedickled bone graft. (d) Metacarpals may also be a donor site. Description of
      sites at the proximal and distal part of the second metacarpal has been used for
      surgical applications. The authors describe a new site at the first metacarpal at
      the radiodorsal or uino-dorsal aspect which may be used as a composite bone-skin
      graft. A clinical application is presented. Clinical use of these pedicles graft
      is discussed and apply mainly for scaphoid nonunion and some case of Kienbock's
      disease. Distal stump reconstruction is possible with the new flap.

PMID- 11582904
TI  - [Reconstruction of the distal radius for primary bone tumors using a non
      vascularized fibular graft (report of 4 cases)].
AB  - We report four cases of primary bone tumour of the distal radius. Follow-up
      averaged ten years with a range of four to 13. Each case underwent excision of
      the tumour followed by reconstruction with a non-vascularised fibular graft. The
      aim of our study was to investigate the carcinologic, functional and radiological
      results at an average of ten years after the initial surgery. There were three
      high grade osteosarcomas and one giant cell tumour of bone. The mean
      postoperative wrist flexion was 45 degrees, extension was 20 degrees, pronation
      30 degrees and supination 50 degrees. Radial tilt was a mean 10 degrees and ulnar
      tilt 15 degrees. All the patients had satisfactory function so as to be able to
      perform activities of daily living and to work. Grip strength was normal in three
      cases and reduced in one. Bone graft healing occurred at a mean of six months
      with a range of from four to nine months. Resection followed by a non
      vascularised fibular graft is an effective way to managing these patients.

PMID- 11582905
TI  - Atypical mycobacterial infections of the hand: report of eight cases and
      literature review.
AB  - INTRODUCTION: Atypical mycobacteria are an uncommon cause of hand infections in
      immunocompetent patients. Diagnosis is often delayed, with consequent increased
      morbidity. Better awareness would allow earlier diagnosis and treatment. MATERIAL
      AND METHODS: Eight patients with atypical mycobacterial hand infections treated
      in our department over a 21 year period have been retrospectively identified.
      Their charts have been searched for the general characteristics of these
      infections, treatment and outcome. Our findings have been compared to the data
      collected from a literature review. RESULTS: These pathogens have caused soft
      tissue infections in otherwise healthy patients. Clinical signs were those of
      chronic finger or wrist synovitis or skin granulomas. Carpal tunnel syndrome was
      a common finding. Diagnosis relied on surgical biopsy. Germ identification
      required specific incubation temperature and media. Antibiotics and synovectomy
      have been the mainstay of therapy. DISCUSSION: In a patient with achronic,
      relapsing, superficial or deep skin infection or tenosynovitis, aquatic and farm
      exposures are important anamnestic keys to diagnosis. Extensive synovectomy is
      both diagnostic and therapeutic. Specific cultures should be ordered without
      delay. Oral pharmacotherapy should be initiated upon clinical suspicion.

PMID- 11582906
TI  - [Anatomical study of the pre-retinacular fat pad of the wrist: application to a
      new surgical approach to the carpal tunnel].
AB  - INTRODUCTION: Decompression of the median nerve in the carpal tunnel by section
      of the flexor retinaculum is the generally accepted treatment for carpal tunnel
      syndrome and is usually effective in relieving the symptoms. Following
      postoperative observations we proposed the hypothesis that incisional pain
      following open carpal tunnel release could be partly explained by injury to the
      fat pad situated between the palmar carpal ligament and the flexor retinaculum.
      METHOD: We performed an anatomical study on 20 fresh adult latex injected upper
      limbs. RESULTS: The sus-retinacularis fat pad is a real anatomical structure,
      clearly delineated and located inside a defined fibrous space with its own
      innervation from the ulnar nerve. It lies in the path of the normal carpal tunnel
      approach. DISCUSSION: Although most postoperative scar tenderness is attributed
      to neuroma formation because of injury to transverse branches of the palmar
      cutaneous nerves, we nevertheless consider that injury to the preretinacular fat
      pad also plays a part. We propose a modified approach to the carpal tunnel. This
      is a safe and simple method which respects the integrity of the sus-retinacularis
      fat pad so as to minimise the extent of scar tenderness.

PMID- 11582907
TI  - [The DASH questionnaire. French translation of a trans-cultural adaptation].
AB  - The DASH (Disability of Arm-Shoulder-Hand) is a self-administered questionnaire
      developed in 1994 by representatives of the Institute for Work & Health (IWH) and
      the American Academy of Orthopaedic Surgeons (AAOS). It measures the physical
      disability and symptoms for all upper limb disorders in a heterogeneous
      population and for acute as well as chronic disorders. The original american
      version has been already tested for reliability and validity. Interest in the
      DASH was raised by several European publications. It appeared that the DASH could
      provide a common measure for upper extremity physical disability in Northern
      America and European countries. For this cross-cultural adaptation, we followed
      the guidelines developed by the Institute for Work & Health and American Academy
      of Orthopaedic Surgeons. Five translations and two "back-translations" were
      compared, aiming to semantic, idiomatic, experimental and conceptual equivalence.
      The final version has been tested in 223 patients presenting a variety of
      traumatic or non traumatic disorders. 208 questionnaires (93%) were valid because
      there was less than 4 missing answers. This final version has been proposed to
      American Academy of Orthopaedic Surgeons in order to be endorsed as an official
      translation. This could improve assessment for international studies by
      establishing standard measures.

PMID- 11582908
TI  - [Atypical Fenton syndrome].
AB  - The case of a patient 41 years old is reported. He sustained a posterior open
      carpal fracture dislocation transcapho-trans-capitate with radius styloid process
      fracture. The original aspect of this observation is that the lunatum was
      enucleated. The treatment was not usual. Capitatum bone was first fixed and
      associated with an external fixation. Proximal row carpectomy was performed in a
      second procedure when removing internal and external fixation, capitatum being
      healed. Follow up is now at four years with a very good radiological and clinical
      result. The patient is working with an intermittent mild pain. Radiographic
      examination demonstrated a very good vascularisation of the capitate head.

PMID- 11582909
TI  - [Ulnar nerve compression and pseudoarthrosis of the medial metacarpal bases].
AB  - A case of compression of the deep branch of the ulnar nerve associated with
      pseudarthrosis of the base of the fifth metacarpal and the upper shaft of the
      fourth metacarpal is reported. The delayed procedure consisted in volar
      decompression of the ulnar nerve by dividing the pisi-hamate ligament and plating
      and grafting of both fractures. The patient achieved marked improvement four
      weeks post-operatively and had complete functional recovery at follow-up of 16
      years after injury without narrowing of the hamato-metacarpal joint despite
      synostosis of the bases of the medial metacarpals.

PMID- 11582910
TI  - Lunatomalacia in association with congenital synostosis between the capitate and
      the hamate.
AB  - This report describes a case of lunatomalacia associated with congenital
      synostosis between the capitate and the hamate, an association not previously
      reported. The case was examined in detail, and compared to the findings in the
      literature including observation regarding prognosis of lunatomalacia.

PMID- 11582911
TI  - [Development of intensive care for pediatric infectious diseases over the last 20
      years].
AB  - Intensive care and especially pediatric intensive care originated in connection
      with fatal forms of infectious diseases, some forty years ago. It has come a long
      way during the last quarter of the past century. Several infectious diseases have
      disappeared in France during this period such as poliomyelitis, dipteria and
      tetanus. Many other are receding. Nevertheless problems remain: serious
      infections by pneumococcus or staphylococcus, maternofoetal infections, whooping
      cough in very young infant. Now, thanks to liver transplantations and intensive
      care, the fatal forms of infectious hepatitis can be overcome in more than 50% of
      the cases. Meanwhile HIV appeared involving intensivists participation. Toxic
      shock, and especially the purpura fulminans, remains a major difficulty. Great
      advances in understanding its mechanisms have been made and it seems today like
      the result of excessive and unsuitable defence reactions. In addition, intensive
      care takes charge of more and more vulnerable ill persons: immunosuppressed,
      extreme premature babies, children who had to undergo heavy operations. In those
      cases, intensive care faces superinfections, nosocomial infections, multi
      resistant germs, related in part to the particular working and environmental
      conditions and an unsuitable use of antibiotics. To conclude, it is necessary to
      optimize the technical and working conditions in intensive care units, to
      strictly observe the well established regulations of hygienics and to develop
      vaccinations.

PMID- 11582912
TI  - [Epidemiology of purpura fulminans and early therapeutic recommendations].
AB  - Despite major advances in pediatrics intensive care, meningococcemia remains an
      important cause of mortality en France (10 to 30%). Parenteral antibiotic given
      immediately is associated with a substantial reduction in mortality. So the
      Conseil superieur d'hygiene publique de France recommend that general
      practitioners should administer promptly, preferably intravenously, whenever
      purpura fulminans is suspected, ceftriaxone (i.m., i.v.), cefotaxime (i.v.) or
      Amoxicillin (i.m., i.v.).

PMID- 11582913
TI  - [Treatment of meningococcal purpura fulminans].
AB  - In France, the incidence of meningococcal infections is increasing. The most
      severe presentation, called purpura fulminans, has a death rate of 20-25%; 5 to
      20% of the survivors need skin grafts and/or amputations. Diagnosis of invasive
      meningococcal infection is very difficult when purpura and "toxic" appearance are
      absent: one should take into account parents' impression of their ill child. This
      diagnosis must be evoked in any child presenting with febrile purpura (like in
      the United Kingdom, parents should be encouraged to use the "tumbler test" to
      identify a vasculitic rash); a fulminant form is to be suspected in the presence
      of only one ecchymosis and signs of infection, remembering that recognition of
      shock is difficult in children. Recently, the Health Authority has recommended to
      administer a third generation cephalosporin promptly (before biological
      investigations) for any child with signs of infection and a necrotic or
      ecchymotic purpura (> 3 mm of diameter), and then to refer the patient to the
      hospital. By grouping the patients from 7 studies, it can be observed that
      preadmission antibiotic administration has a protective effect on mortality (odds
      ratio: 0.36; 95% confidence interval: 0.23-0.56); a negative effect was observed
      in only one of these series. Children with purpura fulminans should be referred
      to a paediatric intensive care unit. Management includes antibiotics, steroids,
      fluid resuscitation and catecholamines (be aware of hypoglycaemia, particularly
      in infants, and hypocalcaemia). Treatment of cutaneous necrosis and distal
      ischemia is difficult and still controversial: antithrombin, protein C, tissue
      plasminogen activator and vasodilator infusion have no proven efficacy. Cases
      must be rapidly notified to the Public Health Service who will institute
      chemoprophylaxis for close contacts. Given the predominance of serogroup B in
      France, we hope that an efficient vaccine will soon become available.

PMID- 11582914
TI  - [Role of host response during severe bacterial infection].
AB  - Explosion of knowledge both in human genomics and in host inflammatory response
      explains the increasing interest in infectious disease genetics over the last 5
      years. However, twin and adoptee studies have suggested more than 15 years ago,
      that host genetic factors are major determinants of susceptibility to infectious
      diseases in humans. Recently, candidate gene studies (association studies) and
      human genomewide analysis have been used to identify infectious diseases
      susceptibility and resistance genes. Rarely, a single gene defect has been
      directly related to devastating consequences such as interferon-gamma receptor
      mutations leading to fatal infections with ubiquitous mycobacteria. For clinical
      practice, gene polymorphisms of specific host immune defence elements appear to
      be of major importance. These genetic variants, which modify the regulation or
      function of the mediators, have been associated with susceptibility and/or
      outcome of severe sepsis and septic shock. All steps of the host response to
      bacteria may be affected by genetic factors. For example, Fc gamma receptor, Toll
      like receptor or mannose binding protein mutations have been shown to modify the
      detection of pathogens leading to pneumococcal severe infections, Gram-negative
      bacteria septic shock, and meningococcal disease, respectively. Polymorphisms of
      cytokine genes (TNF-alpha, TNF-beta, IL-1-ra) have been reported to influence the
      level of secreted mediators and to unbalance the inflammatory cascade.
      Coagulation response to sepsis may also be affected by gene variants such as the
      plaminogen activator inhibitor 1 (PAI-1) common functional polymorphism which
      increases the risk of death from meningococcal infection or severe trauma. The
      impact of these findings on the understanding of infectious disease pathogenesis
      and on the design of future preventive and therapeutic strategies should be
      considerable.

PMID- 11582915
TI  - [Impact of bacterial resistance on severe infections].
AB  - Since many years, the antimicrobial resistance increases as well as for community
      acquired as for nosocomial infections. Antibiotic-resistant pneumococci are
      neither more nor less virulent susceptible strains. Except for immunocompromised
      patients, the outcome of penicillin-resistant pneumococcal infections have been
      similar to those in patients who are infected by susceptible ones. Current levels
      of S. pneumoniae resistance to penicillin and cephalosporin are not associated to
      an increase in mortality in children with meningitis if adequate doses of
      antibiotics are given. Because empiric therapy has changed, antibiotic resistance
      has not been associated with increased mortality. This statement can be extended
      to Meningococcus, for which 32 to 50% of the strains have a decreased
      susceptibility to penicillin. For nosocomial infections, S. aureus is the main
      studied pathogen. Several studies report that in patients with severe diseases
      (bacteremia or pneumonia) methicillin resistance of S. aureus had no significant
      impact on patient outcome after adjustment for different confounders. The main
      risk factor for mortality is the severe underlying diseases rather than the
      resistance as well for methicillin--resistant S. aureus, as for vancomycin
      resistant enterococci, Klebsiella with extended spectrum beta lactamase and
      Enterobacters. Recommendations for controlling epidemiologic surveillance, using
      barrier precautions and limiting the use of antibiotics as well in the hospital
      as in the community must be undertaken.

PMID- 11582916
TI  - [Pediatric deaths due to community-acquired bacterial infection. Survey of French
      pediatric intensive care units].
AB  - A retrospective survey has been conducted in the Pediatric Intensive Care Units
      (PICUs) affiliated to the Groupe Francophone d'Urgence et de Reanimation
      Pediatrique over two years (1999 and 2000). The purpose was to determine the
      number of children aged from 10 days to 18 years who died from community acquired
      bacterial infections and to compare the data to those obtained from official
      surveys (statistics of death from the Institut National de la Sante et de la
      Recherche Medicale) and from the Institut National de Veille Sanitaire as well as
      from punctual studies. Thirty two (60%) PICUs have participated and 100 cases of
      children without known risk factors, dead from community acquired documented
      bacterial infection have been considered for analysis (36 in 1999, 54 in 2000).
      Infants aged between 10 days and 2 months represent 1/3 of the fatalities.
      Neisseria meningitidis is the first pathogen responsible for death (34% including
      10 not documented cases of purpura fulminans). B group is predominant (14/24)
      compared to the C group (6 cases). A lethal infection due to W135 group occurred
      in 2 infants in 2000. Streptococcus pneumoniae is the second pathogen responsible
      for death (28%). None of the cases were due to antibiotic resistant pneumococcus.
      Bordetella pertussis is surprisingly the third pathogen responsible for death
      (13%), all of them being younger than 2 months. Pertussis is the first cause of
      death in infants aged 10 days-2 months. An important increase was observed
      between 1999 (3 cases) and 2000 (10 cases). Meningitis is the first disease
      responsible for death (42%): 26 are related to pneumococcus, 5 to meningococcus
      and 6 to group B streptococcus. Purpura fulminans is the second cause (30%), due
      mainly to group B meningococcus (11 cases). Group C meningococcus accounts for 6
      cases only. One case is related to pneumococcus. Lung infections are a rare cause
      of death (5 cases) and particularly staphylococcal pleuro pneumonia seems to be
      no longer a significative cause of fatality. Toxic shock syndrome is an emergent
      disease responsible for 5 death (2 staphylococcal, 3 streptococcal). These data
      fit with those provided by the Institut National de Veille Sanitaire with respect
      to meningococcal infections and the Renacoq network with respect to pertussis, as
      well as the data provided by a previous GPIP survey on pneumococcal meningitis.
      However, the data provided by INSERM seem not to be relevant. In spite of the
      bias due to a retrospective study and the lack of exhaustivity, this survey
      provides data which could help decision making with respect to new vaccines
      against pneumococcus.

PMID- 11582917
TI  - [Severe bacterial infections in children. Survey by the pediatric mobile
      intensive care unit AP/HP in the Ile-de-France area].
AB  - This study involves 106 infants (neonatal period ruled out), victims of severe
      bacterial infections managed from 1st january 1998 to 30 April 2001 by the four
      paediatric Mobile Intensive Care Unit (P.M.I.C.U.) teams AP-HP in Ile-de-France
      area. 46.2% of the whole infants are primary interventions (home, medical room,
      airport) and primary-secondary interventions (hospital emergencies) whereas 53.8%
      are related to secondary transports of infants who have been hospitalized and
      suffered from severe bacterial disorders complicating their original disease. 51%
      are meningitidis infections, rather due to streptococcus pneumoniae and
      meningococcis, associated with severe infectious purpura. 20.75% are toxic shock
      syndromes in patients suffering from chronic affections (sickle cell anemia),
      acquired or congenital immunodeficiencies; 19.8% of the cases are severe
      bacterial pneumonia (staphylococcal pleuro-pneumopathies, bordetella pertussis
      cough) or surinfected viral infections (VRS bronchiolitis, pneumonia due to
      mycoplasma pneumoniae and para-influenzae III). Authors study various
      characteristics of the two patient's groups, their immediate management by local
      medical team and by the P.M.I.C.U. team, their early term outcome. 65% of
      children recovered apparently without sequelae, 19% died, and 16% healed but with
      significant sequelaes, notably neurological damage. Meningitidis due to
      Streptococcus pneumoniae are particularly severe, because of their prognostic (10
      deaths, 8 severe sequelae among the 26 cases). These observations prompted us to
      recommend early immunization of infants at 2-3 months post natal age by the new
      vaccine conjugated up to 7 valences such as "Prevenar". If this vaccine have been
      available for this patient series, may be avoided 8 deaths, 7 severe sequelae,
      with 1 septic shock syndrome due to streptococcus pneumoniae and another serious
      infection in a homozygous sickle cell disease.

PMID- 11582918
TI  - [Severe neonatal bacterial infections].
AB  - The prognosis of septicemic forms of early and late neonatal sepsis is severe
      with a high rate of mortality especially in premature infants. The evaluation of
      severity is difficult because of the non specificity of the clinical signs and
      mortality seems to be a good means of evaluation. A study was conducted in France
      on the mortality due to infection in neonatal intensive care units and
      neonatology wards during the third trimester 2000. Among 18 units, the mortality
      rate was 9.3% of admissions, corresponding to 11 early onset sepsis and 17
      nosocomial infections. Death in primitive infections is essentially due to group
      B streptococci and E. coli with a more important risk in low gestational age
      infants. The nosocomial infections arise almost only in premature infant.
      Prognosis of infections due to Staphylococcus coagulase negative staphylococci,
      most frequent pathogens is good but mortalities rate is higher for
      enterobacteriacae--40% and for Pseudomonas, 62%.

PMID- 11582919
TI  - [Virulence factors associated with E. coli neonatal meningitis].
AB  - Escherichia coli K1 is the leading cause of gram-negative bacterial meningitis in
      neonates. It is associated with a mortality rate as high as 40%, and more than
      half of the survivors have neurologic sequelae. Bacterial meningitis is the
      result of bacterial translocation from gastrointestinal tract to the blood and
      from blood to the central nervous system. Successful crossing of the BBB by E.
      coli K1 requires (a) a high degree of bacteremia and (b) several E. coli
      determinants contributing to invasion of BMEC such as the K1 capsule, Sfa, Ibe
      proteins, and CNF1. A better understanding for the molecular basis of E. coli K1
      penetration of the BBB could potentially lead to the development of novel
      therapeutic and preventative strategies for E. coli K1 meningitis.

PMID- 11582920
TI  - [Severe infections in children with sickle cell disease: clinical aspects and
      prevention].
AB  - Sickle-cell disease (SCD) is associated with frequent and often severe infections
      as a result of immune function impairment and functional asplenia. Also,
      infection can trigger a vasoocclusive crisis. Pneumonococcal bacteremia and
      meningitis due to S. pneumoniae are often lethal and justify the penicillin
      prophylaxis, which has provided a dramatic decrease in early mortality bacterial
      pneumonia is common in patients younger than four years, with most cases being
      due to S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae.
      Acute chest syndrome is both a difficult differential diagnosis and a common
      concomitant of bacterial pneumonia, because they are often intricated.
      Osteomyelitis is generally due to Salmonella, most often S. enteritidis. Multiple
      foci are common and treatment is difficult, with some patients developing chronic
      osteomyelitis with sequestration. Osteomyelitis is less frequent in developed
      countries and must been differentiated with bone infarction by use of bone
      scintigraphy. Parvovirus B19 infection causes acute erythroblastopenias. Malaria
      does not result in cerebral malaria, but can lead to severe anaemia or
      vasoocclusive crisis, and should therefore be effectively prevented.
      Antimicrobials are generally selected for efficacy against pneumococci
      (septicemia, meningitis), Salmonella (osteomyelitis, meningitis), and M.
      pneumoniae (pneumonia). Prophylactic therapy is of paramount importance and
      relies on long-term or lifelong penicillin therapy started at three months of age
      and no closely-spaced immunizations, most notably against peumococci, hepatitis B
      virus, S. typhi and H. influenzae. Resistant pneumococcal strains have not been
      reported to cause prophylactic treatment failures. New conjugated pneumococcal
      vaccines are effective in protecting very young infants and should therefore be
      used in sickle cell patients.

PMID- 11582921
TI  - [Severe staphylococcal pneumonia in children].
AB  - Between 1986 and 1999, 8 cases of severe pneumonia due Staphylococcus aureus
      strains producing the Panton and Valentine leukotoxin (PVL) were referred to the
      French reference centre for staphylococcal toxaemia. All but one patient were
      children and to determine the clinical features of these pneumonia we conducted a
      prospective surveillance during 1999. Staphylococcal pneumonia was defined
      according to usual standards. All the strains were tested for the gene coding
      PVL, the cases associated with PVL positive strains were considered as study
      group. Nosocomial pneumonia were excluded. 52 cases were referred and 16 were PVL
      positive. These pneumonia occurred in younger patients (median age = 14.8 vs.
      70.1) which were previously healthy (40% of underlying disease in control)
      Remarkable features were the presence of viral infection in the preceding day
      (75% vs. 9%), the frequency of shock (81% vs. 53%), respiratory distress (75% vs.
      53%) and hemoptysia (38% vs. 3%). Leucopenia was present in 79% of cases.
      Mortality was higher in the PVL group (75% vs. 47%). Severe staphylococcal
      pneumonia with shock, leucopenia, hemoptysia and high mortality rate have been
      previously described in children and young adults. We established the
      relationship between this syndrome and the PVL production by S. aureus. We
      believe that viral infection constitute the prerequisite altering the respiratory
      epithelium which secondary allows S. aureus invasion. The necrotizing action of
      the PVL leads to the massive haemorrhagic necrotic pneumonia. Staphylococcal
      necrotizing pneumonia is a new entity which frequency is probably underestimated.
      Further studies are needed to determinate the prognosis factors, the role of S.
      aureus carriage and of viral infections. The description of this new syndrome
      could lead to changes in the management of staphylococcal pneumonia in children.

PMID- 11582922
TI  - [Mortality due to Streptococcus pneumoniae infection in children. A 5-year
      retrospective study in Ile-de-France].
AB  - Streptococcus pneumoniae is the leading cause of community acquired infections.
      We conducted a 5 years retrospective study to assessed mortality of pneumococcal
      infections in children in the area of Paris. Regarding the provided answers, the
      mortality rate is 0.3/100.000/year in the 0-15 years old children. The majority
      of them are toddlers. Only 30% of cases occurred in high-risk children.
      Meningitis was the main cause of death. Pneumococcal resistance to antibiotics
      did not appear as a risk factor of mortality.

PMID- 11582923
TI  - [Severe pneumococcal infections: virulence aspects].
AB  - For many years, the virulence of S. pneumoniae has largely been attributed to its
      anti-phagocytic capsule. However S. pneumoniae elaborate other various factors
      that contribute to virulence. These include the toxin pneumolysin, lytic for all
      eukaryotic cells, and a variety of choline-binding surface proteins; the most
      abundant CbpA and PsaA function as cell surface adhesins, the autolysin LytA is
      responsible for release of lipoteichoic and techoic acids which are mediators of
      host inflammatory response, the role of PspA remains to be demonstrated. These
      factors contribute together to the colonization, protection from phagocytosis,
      invasion, inflammatory response, and tissue damage.

PMID- 11582924
TI  - [Severe Streptococcus pyogenes cutaneous infections].
AB  - Streptococcus pyogenes is the first bacteria encountered in severe cutaneous
      infections in children. They enclose erysipela (papillar derma concerned more
      than hypoderma, lymphatic involvement) and necrotising fasciitis NF (focus on
      fascia and muscles with extension to hypoderma and reticular derma; venous
      thrombosis; hypodermic and aponevrotic necrosis). A skin lesion is the entrance
      of infection: varicella lesions are a major factor of NF. In France, sporadic
      cases in children are observed. The annual incidence of S. pyogenes invasive
      diseases is 1/100,000 children under 5 years of age and 0.6/100,000 children
      under 15 years of age. In North America, resurgence has been notified during the
      past ten years with mortality and morbidity due to NF and toxic shock syndromes.
      Interaction between bacteria and host, natural reservoir, explains the
      physiopathology. During the past ten years, some serotypes have become more
      invasive and virulent. Any cutaneous lesion interrupt the dermal barrier.
      Bacterial wall, proteins M and adhesins permit colonisation. Four pyrogenic
      exotoxins are superantigens; some facilitate inflammation, tissular lesions and
      shock; other participate to bacterial extension. In young children, immune
      response is immature. Albeit causal link between non-steroids anti-inflammatory
      drugs and NF in varicella children was not clearly demonstrated, caution should
      be kept in mind. Diagnosis of erysipela is clinical: sudden appearance of an
      inflammatory zone, most often on legs, with high fever and pain; sometime
      peripheral surelevation, lymphangitis, adenopathia. Other aspects open discussion
      with NF. In NF are in favour, added to high fever, huge pain, erythema and
      oedema: rapid extension of lesions, cutaneous hypoesthesia appearance, gap
      between intense severe general status (toxic shock syndrome) and paucity of local
      signs. NF is a medico-surgical emergency. Early surgery with complete excision of
      necrotic tissues permit survival. Magnetic resonance is useful in subacute NF.
      Microbiological diagnosis is possible in 20 to 80% of cases, using combined
      methods. Blood cultures identify the bacteria in 5 to 20%, skin lesion samples in
      30%. Local samples are less useful even with modern techniques. Therapeutic
      strategy depends on initial diagnosis. Intra-venous antibiotics are necessary:
      penicillin (G, A or M) is first line therapy. In erysipela, ten days allow a
      rapid cure without sequellae. In NF, antibiotics are associated with intensive
      care and surgery. A late diagnosis, a too late surgery explain 16 to 36% of
      deaths encountered.

PMID- 11582925
TI  - [Clinical aspects of streptococcal and staphylococcal toxinic diseases].
AB  - Staphylococcus aureus and Streptococcus pyogenes produce a lot of toxins, some of
      them responsible for specific diseases. Staphylococcal food poisoning is due to
      ingestion of enterotoxin containing food. Seven toxins have been isolated so far.
      Generalized exfoliative syndrome is related to exfoliatin. Young children are
      particularly affected. The disease consists in a cutaneous exfoliation usually
      limited with a favourable outcome. The mucus membranes are not involved. The nose
      or pharynx are the most usual portal of entry. Staphylococcus aureus is not grown
      from the bullae. Severe extensive forms have been observed particularly in
      neonates (Ritter's disease). Bullous impetigo is also due to exfoliatin. It
      consists in the presence of a restricted number of cloudy bullae, from which
      staphylococcus can be grown. It is a mild disease with a favourable outcome
      within a few days. Scarlet fever is related to the streptococcal erythrogenic
      toxins. The classic form of the disease is presently rare. This disease may be
      related to staphylococcus as a complication of arthritis, osteomyelitis or wound
      super-infection. Bacteremia is usual. Staphylococcal scarlet fever is not related
      to exfoliatin as previously believed, but to enterotoxins or TSST-1, so it seems
      to be an abortive form of toxic shock syndrome. Toxic shock syndrome is defined
      as a multi organ failure syndrome with a rapid onset, fever, rash followed by
      desquamation, vomiting and diarrhea, hypotension, conjunctivitis and strawberry
      tongue. The disease is related to an infection or colonisation with a toxin (TSST
      1) producing strain of Staphylococcus aureus. Enterotoxins (mainly C) may be
      involved. The disease may occur in childhood, sometimes after superinfection of
      varicella. The mortality is low (5%) and mainly due to ARDS or cardiac problems.
      Erythrogenic toxins produced by Streptococcus pyogenes are involved in a
      streptococcal form of toxic shock syndrome with a quite similar presentation. In
      most cases however, a cutaneous or soft tissue infection is at the origin.
      Necrotizing fasciitis complicating varicella is a classic cause in children.
      Bacteremia is often observed. The mortality rate is as high as 60%. The
      streptococcal strains involved in north america use to produce the toxin
      erythrogenic A, the european cases seem to be more related to strains secreting
      the B toxin with a dysregulation of the mechanisms which control the secretion of
      the toxin. Staphylococcus strains producing the Panton and Valentine leucocidin
      are responsible for chronic or relapsing furonculosis and above all for a very
      severe necrotizing pneumonia observed in children and young adults presenting as
      an acute respiratory distress syndrome with leucopenia, hemoptysis and shock
      carrying a heavy mortality rate. Besides these specific diseases, staphylococcal
      and streptococcal toxins may be involved in some syndromes of unknown origin, in
      which the intervention of superantigens seems very likely. Kawasaki syndrome is
      among them as strains producing staphylococcal and streptococcal toxins have been
      grown from patients with Kawasaki syndrome. In the same way, the intervention of
      toxins is suspected in the determination of sudden infant death syndrome and
      atopic eczema.

PMID- 11582926
TI  - [Staphylococcal and streptococcal pediatric toxic syndrome from 1998 to 2000.
      Data from the National Center for Staphylococcal Toxemia].
AB  - The clinical and microbial settings of staphylococcal and streptococcal toxemia
      in pediatric patients were investigated by the French National Reference Center
      for Staphylococcal Toxemia. From 1998 to 2000, the number of cases was low in
      regard to the usual putative incidence of these toxemia; this low incidence was
      probably linked to the passive collection of cases. The most significant finding
      was the evidence of skin infections as the source of the majorities of
      staphylococcal toxic shock syndrome and staphylococcal scarlet fever as described
      for streptococcal toxic shock syndrome or nosocomial suppurative infections.
      Moreover, most of scalded skin syndrome were from pediatric patients and were
      exceptional in adults. For other syndromes, no significant original findings were
      observed.

PMID- 11582927
TI  - [Post-diarrhea hemolytic-uremic syndrome: clinical aspects].
AB  - Every year in France, about 100 children, most of them less than 3 years old,
      have typical diarrhea-associated HUS (D + HUS). Evidence of exposure to verotoxin
      producing E. coli (VTEC), mostly the O157: H7 serotype, is demonstrated in about
      85% of cases. A prodromal illness of acute gastroenteritis with diarrhea, often
      bloody, precedes the HUS by 1 to 15 days. HUS onset is sudden, with the typical
      association of hemolytic anemia with fragmented red blood cells, thrombocytopenia
      and acute renal insufficiency. Involvement of other organs than the kidneys may
      occur, such as severe hemorrhagic colitis with rectal prolapse, bowel wall
      necrosis or secondary stenosis, acute pancreatitis, central nervous system
      involvement which determines the vital outcome. Early accurate supportive
      treatment allows a current mortality rate below 5%, with most deaths due to
      central nervous system involvement. Five to 10% of children develop end stage
      renal disease, rarely directly, more often after having recovered some renal
      function with chronic renal insufficiency during a few years. After 15 or more
      years follow-up, at least one third of patients have some degree of proteinuria
      and/or hypertension, and eventually chronic or end stage renal failure.
      Predictive features of poor renal outcome at the acute phase are severe
      gastrointestinal involvement, severe CNS involvement, polyncleosis over
      20,000/mm3, and duration of initial anuria longer than one week. The role of VTEC
      in D + HUS makes the disease a public health problem. Preventive measures are
      essential.

PMID- 11582929
TI  - [Dysmorphic syndromes at birth: what to do?].
AB  - Approximately 3% of newborn infants present with minor or major defects for which
      the pediatrician's advice is required. The diagnosis approach of a dysmorphic
      syndrome at birth relies upon a systematic four-step evaluations including: 1)
      family history; 2) information on the perinatal history; 3) complete physical
      examination with careful description of the morphological anomalies; 4) oriented
      imaging, laboratory and/or cytogenetic investigations. In many cases the
      regrouping of the different information will lead to the diagnosis of a precise
      malformation syndrome. However the etiological diagnosis may also be difficult at
      birth and will necessitate a regular follow up in order to take into account the
      evolution of the defects and the occurrence of additional clinical signs.

PMID- 11582928
TI  - [Hemolytic-uremic syndrome: microbiological aspects].
AB  - Escherichia coli O157: H7 became an important pathogen starting in the early
      1980s. It has caused epidemics and sporadic cases of often bloody diarrhea which
      may progress to severe hemolytic and uremic syndrome or thrombotic
      thrombocytopenia purpura. E. coli O157: H7 is mainly transmitted in food, water
      and interhuman transmission, but direct animal-to-man transmission has also been
      documented. E. coli O157: H7 can adhere tightly to the enterocyte brush border
      (eae gene) and produce verotoxins or Shiga-like toxins and hemolysine (ehxA
      gene). Diagnosis of E. coli O157: H7 infections is based on evidencing the germ
      in stools and/or by identifying the genes coding for verotoxins or by serology
      which increased serum titre of specific antilipopolysaccharide antibodies.
      Antidiarrheal drugs and antibiotics have little place in the treatment of bloody
      diarrhea. This public health problem, requires careful identification of animal
      reservoirs and improved population education in food hygiene.

PMID- 11582930
TI  - [Piercing and tattooing: from the body to the master piece].
AB  - In recent years, new uses of the body have taken place among youths. Body art has
      become democratic and reaches more and more heterogeneous groups of customers.
      Considered for a long time as a primitive attribute, tattooing has come out from
      the 'underground' for an open display. The many uncertainties of our modernity
      appear to incline young people to knock around their bodies. From circumcision to
      piercing and tattooing, all these body writings appear as religious, initiatory
      or community rituals, more in keeping with a primitive law rather than with an
      individual revolt.

PMID- 11582931
TI  - [Neuroblastoma a century after Pepper: which are the genes?].

PMID- 11582932
TI  - [Assessing the cost of the first episode of bronchiolitis].
AB  - BACKGROUND: Each year, a quarter of the children younger than 24 months has
      respiratory syncytial virus bronchiolitis. The morbidity among high-risk infants
      and the possible association with the development of asthma lead to propose
      preventive measures whose cost-effectiveness relationship is unknown. The present
      work was aimed at measuring costs of a first attack of bronchiolitis. METHOD: For
      children less than two years visited in the emergency department, direct and
      indirect costs were measured according to the 'Securite Sociale' prices.
      Associated morbidity, the management of care (inpatient versus outpatient),
      outpatients' outcome two weeks after the visit, socioeconomic data were recorded.
      RESULTS: One hundred eighty three children have been studied. The length of stay
      for 40 hospitalizations was 7.6 +/- 4.3 days. Direct costs were 37,200 +/- 22,000
      FF for inpatients, and 1286 +/- 633 F for outpatients. For 113 outpatients'
      families, indirect costs were 49 working days lost. The way the child was looked
      after and the unemployment rate in the study were similar to data provided by the
      National Institute of Statistics and Economic Studies. CONCLUSION: Because of the
      variability of the hospitalization rate from one setting to another, overall
      costs of the epidemic cannot be evaluated. For the policymaker, the greatest
      costs come from the outpatient care. Others studies will be necessary to evaluate
      the price of future preventive measures.

PMID- 11582933
TI  - [Systematic screening of deafness at a maternity ward using evoked otoacoustic
      emissions: practical aspects and parental attitudes].
AB  - OBJECTIVE: Evaluation of the feasibility and parental attitudes towards a hearing
      screening programme using evoked otoacoustic emissions, implemented in a
      maternity ward in France. METHODS: A hearing screening test using transiently
      evoked otoacoustic emissions (TEOAE) was proposed to each baby, and an anonymous
      questionnaire was given to parents to assess their attitudes towards the
      screening procedure. RESULTS: Although the refusal of the test reached 16%
      (mainly during the first two weeks of the program), more than 92% of parents
      judged the test as being useful, and 65% wished it to be systematically done.
      However, nearly 35% of parents admitted to have a low level anxiety about being
      unnecessarily worried by the test results. One hundred and twenty-four babies
      were screened. Fifty three per cent of the tests have been performed in less than
      ten minutes, with an average of 12.2 minutes. This duration does not include
      delays due to programme and babies management. False positive rate (uni or
      bilateral fail) was 10.5% at the first stage. Repeating the test before discharge
      decreased the false positive rate to 6.5%. CONCLUSION: Although limited in time,
      this study shows that a systematic hearing screening programme using TEOAE is
      possible and should be done in France. False positive rate was below 7%, and the
      test was considered as useful by more than 90% of parents, although knowledge
      about deafness in childhood and its consequences were clearly insufficient.

PMID- 11582934
TI  - [Assessment of the use of aminoglycosides at a pediatrics hospital].
AB  - MATERIALS AND METHODS: Three surveys were successively carried out regarding
      aminoglycoside use: one analysis of amikacine prescriptions in the most
      prescribing clinical wards and two surveys among nurses and physicians
      respectively on prescribing, administering and monitoring aminoglycosides.
      RESULTS: On 43 amikacine prescriptions analyzed in a month, one daily dose
      infusion in 30 minutes was observed in most of the patients (70%), doses and
      indications matched most often the official license. Half of patients treated for
      more than five days had no drug level monitoring. Sample collection by nurses was
      very erratic making results obtained not interpretable. CONCLUSION: Subsequently,
      guidelines regarding aminoglycoside use were designed by the interest group,
      approved by the drug committee and sent to all hospital prescribers and nurses.

PMID- 11582935
TI  - [Main timetables of pediatric emergencies. Experience at the Lenval hospital in
      1999].
AB  - OBJECTIVE: The purpose of the present study was to determine the main schedules
      of a visit in a paediatric emergency ward. PATIENTS AND METHODS: A prospective
      survey concerning the main schedules of the children examined in the paediatric
      emergency ward of the Lenval's hospital in Nice in 1999 was implemented. The
      study was conducted over a period of 84 days, one week per month, and included
      6038 children analysed recording to the following criteria: 1) duration of the
      waiting; 2) duration of the radiological period; 3) duration of the medical
      advice and/or treatment period; 4) total time course of the visit. RESULTS: Data
      were collected in 66.6% of all cases for waiting (n = 4022), 52.1% for medical
      advice (n = 3149), in 44.1% for radiological time (n = 833 of 1888 children
      having radiological examination), in 58.1% for the total time course of the
      visit. Waiting for not severe emergencies was about one time out of three less
      than five minutes, more than one time out of two less than 15 minutes, and more
      than three times out of four less than 30 minutes. Mean radiological time course
      was 20 to 25 minutes. Mean medical advice was 15 minutes, for medical
      consultations such as surgical ones. Total time course of the visit was less than
      30 minutes in 23.1% of all cases, 30 to 60 minutes in 38.5%, one to two hours in
      31.3%, two to four hours in 6.8%, and more than four hours in 0.3% of all cases.
      Mean total time course of the visit was 45 minutes for medical emergencies and 55
      minutes for surgical ones. CONCLUSION: This study shows the main schedules of a
      visit in a paediatric emergency ward which took care of 26,726 children in 1999.
      The results of this survey confirmed that waiting before consultation, for not
      severe emergencies, is sometimes long or very long because of a constant
      increasing number of patients and their preferential breakdown according to
      specific periods (weekends, public or school holidays, winter) which are the
      result of demographic, social and economic changes. At present, the only
      available possibility to control both phenomena consists in adjusting and
      adopting medical tools and staffs to crowds and flows. This study also confirms
      the usefulness for paediatric emergency ward to have a short hospitalization
      unit.

PMID- 11582936
TI  - [Severe upper airway obstruction in infectious mononucleosis: a life emergency].
AB  - BACKGROUND: Upper airway obstruction can represent a severe, life-threatening
      complication of infectious mononucleosis. We report a rare case of airway
      obstruction in a child with infectious mononucleosis associated with herpes virus
      infection, and we discuss management strategy that can be proposed in such cases.
      CASE REPORT: A 9-year-old girl was hospitalised in intensive care unit for
      obstructive dyspnea during infectious mononucleosis. Despite five days of
      corticosteroids and tracheal intubation, persistent pharyngo-tonsillar
      tumefaction led us to perform a surgical adenotonsillectomy. This latter
      treatment allowed immediate tracheal extubation and a rapid recovery. Histology
      showed a herpes virus infection associated with infectious mononucleosis.
      CONCLUSION: Maintaining airway opening in infectious mononucleosis needs
      sometimes to use instrumental interventions: nasal trumpet, endotracheal
      intubation, even tracheostomy. Early tonsilloadenoidectomy may relieve airway
      obstruction and allow a rapid recovery in the most severe cases. Airway
      obstruction in infectious mononucleosis may be aggravated by concomitant herpes
      virus infection that should be searched for in this situation, in order to adapt
      the treatment.

PMID- 11582937
TI  - [Diagnostic trap and difficulties of genetic counseling in a family with
      neuromuscular disease carriers].
AB  - BACKGROUND: Recent advances in the field of molecular genetics have provided
      useful tools for the diagnosis of neuromuscular disorders. Genetic counselling
      for many of these conditions may, however, be fraught with difficulties. CASE
      REPORT: The patient, two paternal uncles and a paternal aunt presented with
      clinical and electromyographic evidence of type III spinal muscular atrophy
      despite an autosomal dominant-like pedigree. The diagnosis was confirmed by
      genetic testing for the SMN deletion. As the proband's mother was pregnant at the
      time of presentation of the affected child, a prenatal diagnostic test was
      performed. The deletion was not found in the DNA extracted from the trophoblast
      and the pregnancy proceeded to full term, and a normal child. At the same time, a
      first cousin of the proband was found to have a clinically similar condition. He
      had not the SMN deletion. He presented with electrophysiological and pathological
      features of limb-girdle muscular dystrophy. Genetic testing revealed a homozygote
      del T521 mutation of the gama-sarcoglycan gene. CONCLUSION: To provide accurate
      genetic counselling, it is essential to get precise data on family background and
      diagnostic confirmation for each affected relative to avoid missing the
      possibility, albeit rare, of several neuromuscular disorders within a family.

PMID- 11582938
TI  - [Post-varicella thrombosis and factor V Leiden mutation].
AB  - BACKGROUND: Varicella is a benign infectious disease that is rarely complicated
      by thrombosis. Factor V Leiden (FVL) mutation is presently recognized as the most
      common inherited cause of thrombosis. From a case report the link between
      varicella associated thrombosis and FVL is discussed. CASE REPORT: An eight year
      old boy was admitted on 15th day of a varicella infection for difficulty to walk
      and painful legs. Doppler ultra sound of the lower limbs venous system showed
      thrombosis of the left iliac vein and femoral veins. Thrombophilia work-up
      revealed a FVL heterozygotic status for the patient. Biological screening for
      molecular abnormalities associated with thrombophilia led to the detection of a
      heterozygous inherited FVL mutation in the patient. Response to heparine followed
      by oral anticoagulant treatment was good. CONCLUSION: Thrombosis associated with
      varicella in child is a rare event. We recommend to realize a thrombophilia
      screening in such patients. We also support varicella vaccination of children
      identified as having constitutional prothrombotic disorders like FVL mutation.

PMID- 11582939
TI  - [Severe autoimmune immunoglobulin A hemolytic anemia in a 10-month-old infant].
AB  - CASE REPORT: A ten-month-old boy presented with a severe auto-immune hemolytic
      anemia. Direct antiglobin test was positive only for IgA class autoantibodies. He
      recovered with a high dose corticosteroid treatment. CONCLUSION: IgA class
      autoantibodies should be searched for in the case of a high suspicion of auto
      immune hemolytic anemia with negative direct antiglobin test for IgG and
      complement. Corticosteroid treatment is most often successful.

PMID- 11582940
TI  - [Multiple sclerosis: pathogenesis and manifestations in children].
AB  - Multiple sclerosis (MS) is rare in children and occurs exceptionally before ten
      years. Sex ratio (girl/boy) is around 2.5 to 3, higher than in adults. Brain stem
      dysfunction and meningeal symptoms are more commonly first manifestations of the
      disease than in adults. Optic neuritis is also a frequent early manifestation.
      The etiology of the disease remains unclear and none of the advanced hypotheses
      (infectious, genetic, environmental) can by themselves explain its occurrence.
      There is a genetic susceptibility which is probably linked to many genes leading
      to a low related risk (less than two). A viral trigger mechanism in a person with
      a genetic predisposition is possible. New therapies result from a better
      understanding of the closed immune mechanisms of the disease.

PMID- 11582941
TI  - [Development of specific immunity in prenatal life].
AB  - The various defense mechanisms of specific immunity, which involves the T and B
      lymphocytes and the antigen presenting cells, are gradually developed during
      intra-uterine life. The first hematopoietic organ is the yolk sac which appears
      at the 4th week of development. Thereafter, the hematopoiesis takes place in the
      fetal liver (from the 6th week) followed by the bone-marrow during the 3rd
      trimester. The differentiation of the T lymphocytes begins around the 10th week.
      The thymic epithelial rudiments appear during the 7th week and the thymus
      migrates to its definitive place at ten weeks. It is then colonized by the T cell
      precursors, which there undergo their maturation process. From the 12th week of
      development, mature T cells are readily detectable in lymphoid organs and fetal
      blood. The maturation of B cells, which occurs firstly in fetal lever, and
      thereafter in bone marrow begins also early in fetal life (12th week). The
      antigen presenting cells, the precursors of which are detected in the yolk sac as
      soon as 4-6 weeks, are normally present and functional in secondary lymphoid
      organs as soon as 12 weeks. Thus, the specific immune response appears possible
      by the end of the 1st trimester. However, the naive nature of T and B lymphocytes
      is responsible for a delayed, slow and relatively ineffective primary response.
      This observation explains the particular susceptibility of neonates, especially
      premature neonates to bacterial and viral infections. The various antigenic
      stimulations and T/B cell cooperations allow a complete maturation of the immune
      system during the first years of life.

PMID- 11582942
TI  - [Radiologic case of the month].

PMID- 11582943
TI  - [Practical use of local anesthetics in children].
AB  - Simple techniques of local analgesia applicable in children either in the medical
      office or in the emergency room by non-specialist practitioners are described:
      infiltration of the skin, topical anaesthesia of the skin, whether intact or
      damaged, topical anaesthesia of the mucosae.... In addition safety rules, early
      signs and treatment of local anaesthetics intoxication are underlined.

PMID- 11582944
TI  - [Are there still valid indications for carotid stents?].

PMID- 11582945
TI  - Nonatherosclerotic disease of the cervical arteries: role of ultrasonography for
      diagnosis.
AB  - On the basis of morphological and hemodynamic criteria, color-coded duplex
      sonography enables diagnostic evaluation of non-atheromatous lesions of the
      cervical arteries. Ultrasonography is the method of first choice for Takayasu's
      arteritis, radiation angiopathy, and common carotid artery dissections. Internal
      carotid and vertebral artery dissections are detected in up to 95% and 79%,
      respectively; in some of these cases, however, ultrasonography delivers
      unspecific findings so that dissections can only be confirmed when typical
      clinical symptoms are present, too. Detection of vasospasms of the cranial
      arteries is extremely difficult, on account of their tendency for rapid
      regression; however, sonography is in principle a suitable method. In cases of
      fibromuscular dysplasia ultrasound has furnished less positive results on account
      of the unfavourable localisation for duplex sonography. As the disease has a
      relatively good prognosis, only symptomatic cases need to be detected. On the
      whole, sonography is a suitable method for the diagnosis of nonatherosclerotic
      diseases of the cervical arteries.

PMID- 11582946
TI  - [Macroangiopathy in diabetes mellitus].
AB  - In patients with diabetic angiopathy until today, no histological nor
      histochemical evidence has been found to define a specific type of diabetic
      arteriopathy. Consequently, diabetic arteriosclerosis is considered as a more
      serious form of atherosclerosis characterized by its premature onset.
      Hyperglycemia is assumed to be the crucial pathophysiological cause of the
      development of macro- and microangiopathy in diabetes mellitus. Apparently,
      hyperglycemia has a direct toxic influence on the arterial wall by increased
      accumulation of irreversible glycosylation end products, and secondly, it
      provokes endothelial dysfunction. The frequently occurring ulcerations of the
      diabetic foot are primarily caused by neuropathy; however, peripheral vascular
      disease (PVD) is often associated. The risk of suffering from PVD in diabetic
      patients is approximately four-fold. Usually, the distal segments of the lower
      leg arteries are concerned, where reconstructive intervention is complicated or
      even impossible. Diabetes is considered as an independent risk factor for cardio-
      and cerebrovascular diseases with almost twice as high rates for recurrent
      myocardial infarction, and a 3.7 fold higher relative risk for stroke in
      diabetic, compared to non-diabetic patients. This review looks at the
      correlations between hyperglycemia and arteriosclerosis, but also the treatment
      options in diabetic patients. Until now, there is no evidence for an association
      between an optimal control of blood glucose levels and a decrease in the risk of
      coronary heart disease, stroke, or PVD. In contrast, an attenuation of
      microvascular lesions is achieved by stringent control of blood glucose levels.
      Thus, although the development of macroangiopathy may not be significantly
      influenced, the conduction of a stringent control regimen of plasmatic glucose
      levels is advisable.

PMID- 11582947
TI  - Myointimal hyperplasia and sympathetic reinnervation following local cold injury
      and rapid rewarming in the rabbit central ear artery.
AB  - BACKGROUND: Functional and pathological improvements following rapid rewarming in
      42 degrees C water was compared with alterations following slow thawing at room
      temperature (22 degrees C) after frostbite (-9 degrees C, 15 minutes) in vivo of
      the rabbit central ear artery. METHODS: Following two to ten weeks of in vivo
      regeneration, vascular segments were tested in vitro. Maximal and dose-dependent
      isometric contractions were induced by exogenous noradrenaline. Sympathetic
      nerves in the vascular wall were stained with glyoxylic acid. Vascular ring
      segments were stained with haematoxylin and eosin. RESULTS: Following slow
      thawing, the total uptake, the K+ evoked and the spontaneous release of
      [3H]noradrenaline in the sympathetic nervous system were strongly reduced two
      weeks after freezing, with a subsequent increase to control level within 3-4
      weeks. After rapid rewarming the total uptake, the spontaneous release and the K+
      evoked release of [3H]noradrenaline commenced earlier such that after ten weeks
      the level was twice as high as following slow rewarming. The glyoxylic acid
      induced catecholamine fluorescence in sympathetic nerves, revealed an earlier
      regeneration after rapid rewarming. Haematoxylin and eosin-stained segments
      revealed less intimal hyperplasia three to 20 weeks after rapid rewarming than
      after slow thawing. CONCLUSION: Rapid rewarming of in vivo frozen arteries in
      warm water (42 degrees C) did not prevent immediate vasoparalysis and
      degeneration of sympathetic nerves. However, nerve regeneration occurred earlier
      and with higher tissue nerve densities as compared to tissue that had been slowly
      rewarmed. Myointimal hyperplasia was less pronounced after rapid rewarming.
      Abnormal sympathetic nerve function and myointimal hyperplasia, as observed in
      this study, may contribute to a greater understanding of sequelae in the human
      body following frostbite.

PMID- 11582948
TI  - Coagulation and fibrinolysis in chronic venous insufficiency.
AB  - BACKGROUND: Varicose veins (VV) are common, but only some patients will develop
      chronic venous insufficiency (CVI) with skin changes or venous ulcer. The
      pathophysiology of venous ulcer development is complex, and may involve
      abnormalities in coagulation, fibrinolysis and proinflammatory cytokines. The
      purpose of this study was to correlate plasma markers within these systems and
      skin pathology. METHOD: A group of twenty consecutive patients with active or
      recent venous ulcer were matched for sex and age with further three groups of
      individuals i.e. controls and patients with VV with and without skin changes
      respectively. Blood samples were analysed for hemoglobin (HB), total platelet
      count (TPC), C-reactive protein (CRP), activated partial thromboplastin time
      (APTT), prothrombin complex (PT), fibrinogen, interleukin-1 beta (IL-1 beta),
      tumor necrosis factor alpha (TNF alpha), D-dimer, tissue plasminogen activator (t
      PA), plasminogen activator inhibitor 1 (PAI-1), prothrombin fragments 1 and 2 (F1
      + 2), and thrombin antithrombin III complex (TAT). RESULTS AND CONCLUSION: There
      was an increase of systemic levels of PAI-1 activity and tPA with progressive
      skin pathology in patients with CVI, and in the group with active ulcer there was
      an elevation of F1 + 2. Those findings could reflect a defect fibrinolysis, a
      thrombotic potential or a damaged endothelium.

PMID- 11582949
TI  - Thrombangitis obliterans: leucocyte subpopulations and circulating immune
      complexes.
AB  - BACKGROUND: The etiology of thrombangitis obliterans is still unclear. Although
      cellular infiltration of the vessel wall is known, no studies on peripheral blood
      mononuclear cells are reported. Therefore, we assessed leucocyte subpopulations
      and circulating immune complexes in patients with thrombangitis obliterans and a
      control group of normal people. PATIENTS AND METHODS: 31 patients (40 +/- 2
      years, 24 male, 7 female) with thrombangitis obliterans were included, based on
      the following criteria: age of manifestation, acral ischemia in legs and arms,
      previous thrombophlebitis or phlebitis saltans. Manifestation of atherosclerosis
      or other vasculitic manifestations were excluded. Leucocyte subpopulations,
      levels of C-reactive protein (CRP) and circulating immune complexes (CIC) were
      investigated. An age-matched control group (n = 25) was recruited from voluntary
      blood donors. RESULTS: Leucocyte counts in the thrombagitis group (mean +/- SD:
      10,839 +/- 782/nl) were significantly different from the control group (6205 +/-
      414/nl, p < 0.0001). The same was true for absolute counts of granulocytes,
      monocytes and lymphocytes. The results were independent from CRP, which was
      elevated only in 6 patients. Relative counts of naive helper T-cells were
      significantly lower in the patient group. HLA-DR expression on B-cells was lower
      on the patients' lymphocytes. The concentrations of IgA, IgG and IgM in CIC were
      higher in the thrombangitis patients compared to the control group. C1q-binding
      capacity and phosphatidylserine antibodies showed no differences. CONCLUSIONS:
      Patients suffering from thrombangitis obliterans show alterations of leucocyte
      counts and their subpopulations as well as alterations of the humoral (IgCIC)
      immune system.

PMID- 11582950
TI  - Therapy of deep vein thrombosis with low molecular weight heparin, leg
      compression and immediate ambulation.
AB  - BACKGROUND: Traditionally, patients with acute deep vein thrombosis (DVT) are
      treated with strict bed rest for several days to avoid clots from breaking off
      and causing pulmonary emboli. The purpose of this study is to give a precise
      estimate of short term complications like pulmonary embolism, bleeding, heparin
      induced thrombocytopenia (HIT) and death in a cohort of consecutive patients who
      were admitted because of acute symptomatic DVT, all treated by compression and
      walking exercises instead of conventional bed-rest and nearly all by low
      molecular-weight heparin. PATIENTS AND METHODS: In 1289 consecutive patients the
      following five endpoints were registered for the period of hospital-stay: 1.
      Frequency of pulmonary embolism (PE) at admission (V/Q lung scan), 2. Frequency
      of new PE's after 10 days (second lung scan), 3. Fatal events (autopsy), 4.
      Frequency of malignant disease, 5. Bleeding complications and HIT. RESULTS: 1.
      190/356 (53.4% of iliofemoral, 355/675 (52.6%) of femoral and 84/239 (35.1%) of
      lower leg vein thrombosis showed PE (difference iliofemoral and femoral versus
      lower leg DVT p < 0.001). Two thirds of these PE were asymptomatic. 2. New PE
      after 10 days in comparison to the baseline scan occurred in 7.4%, 6.4% and 3.4%
      respectively. 3. Fatal events, all investigated by autopsy, were caused by PE in
      3 patients aged over 76 years (0.23%), by malignant diseases in 12 (0.9%) and due
      to other causes in 2 (0.15%). 4. 232 patients (18%) had associated malignant
      diseases, from which 33% were detected by our screening. 5. Non-fatal bleeding
      complications were seen in 3.3%, including 5 patients (0.4%) with major bleeding.
      Three patients (0.2%) suffered from HIT II. CONCLUSION: The low incidence of
      recurrent and fatal pulmonary emboli in this series affirms the value of early
      ambulation with heavy leg compression in patients with symptomatic acute leg deep
      venous thrombosis. In addition, the presence of pulmonary emboli in one-third of
      those with calf vein thrombi emphasizes the importance of fully diagnosing and
      treating calf clots.

PMID- 11582951
TI  - Management of hypovascularized wounds not responding to conventional therapy by
      means of free muscle transplantation.
AB  - BACKGROUND: Chronic ulceration as a complication of arteriosclerotic disease,
      venous congestion or diabetes mellitus is still a serious clinical problem,
      resulting in immobilization, extended hospitalization and cost-intensive
      treatment. Other than standard conservative treatment protocols or early
      amputation, microsurgical free transfer of well vascularized muscle tissue onto
      chronic wounds can induce angiogenesis and improve wound healing even in the
      hypovascularized wound. PATIENTS: From 1993-1999 we treated 12 patients (mean
      age: 46 years) with vascular ulcers of the lower extremity with free muscle or
      fasciocutaneous tissue transfer. RESULTS: The average hospitalization was 51.4
      days. The perioperative mortality was zero. In one patient with factor V
      deficiency a partial flap necrosis occurred. Two revisions of the micro
      anastomoses had to be performed. Two seromas occurred at the donor site. No
      secondary flap loss was observed. Extremity or stump length preservation was
      achieved in all cases. CONCLUSIONS: Optimal postoperative treatment with
      physiotherapy and orthopaedic shoe support is important. If all these factors are
      present and if the patient is highly motivated a reintegration into normal life
      can be achieved.

PMID- 11582952
TI  - Long-term results of systemic thrombolysis therapy in aorto-iliac occlusive
      disease.
AB  - BACKGROUND: Long term results of systemic lysis therapy with ultrahigh-dose
      urokinase (UHUK) in reopening aorto-iliac occlusive disease have not yet been
      evaluated. This prospective trial investigates the long-term primary patency
      rate, the rate of complications and assesses the role of different expected
      influence parameters on the primary patency rate. PATIENTS AND METHODS: 72
      patients with aorto-iliac occlusive disease received daily intravenous infusions
      of UHUK either until reperfusion or--after at least 3 cycles--no progress in
      recanalization could be stated on two consecutive days by duplex scanning.
      RESULTS: Systemic lysis therapy was morphological at least partially successful
      in 44 patients (61.1%). Concomitant percutaneous transluminal angioplasty was
      performed in 41 patients (56.9%), surgery in 7 patients (9.7%) and both in
      further 5 patients (6.9%). In patients without surgery hemodynamical success
      could be achieved in 39 patients (54.2%) and even more important clinical success
      in 51 patients (70.8%). Compared to baseline results patients improved
      significantly in ankle/brachial pressure index and in Fontaine stages (p <
      0.001), the same results could be seen after a mean follow-up period of 62
      months. Thrombolysis was complicated in 4 patients (5.6%) by macroembolizations
      but no major bleedings or deaths occurred. Primary patency was 76%, 64%, and 43%
      after 1, 5 and 10 years. Male sex and distal localization were significantly
      correlated with lower primary clinical patency. CONCLUSION: Systemic lysis
      therapy is an alternative to surgical intervention in acute and subacute aorto
      iliac occlusive disease, because it offers acceptable long-term results with a
      low rate of complications.

PMID- 11582953
TI  - [Embolization of aneurysma spurium of the superior gluteal artery].
AB  - While for the surgical treatment there are the transgluteal and the
      retroperitoneal approach, the alternative radiological modality is less invasive.
      It is performed by a from contralateral placed guidant-catheter in combination
      with a tracker catheter with the possibility of transcatheter embolization with
      liquid, particles or coils. The rate of success is high, complications are seldom
      and the hospital stay is short. Both modalities can and should be used
      complementary. In the case of an intractable acute hemorrhage transcatheter
      embolization should be used firstly.

PMID- 11582954
TI  - Necrosis of the tongue and unilateral blindness in temporal arteritis.
AB  - While blindness is one of the typical clinical presentations of temporal
      arteritis, tongue necrosis, on the other hand, is an unusual complication of the
      disease. An 80 year old male patient presenting a sudden massive swelling of the
      tongue was admitted to the Hospital of Yverdon. The swelling rapidly progressed
      to a complete necrosis of the tongue within a few days. The clinical
      presentation, the dramatic evolution of the necrosis, and sudden unilateral
      blindness despite prompt treatment confirmed our diagnosis of temporal arteritis.
      However, all the examinations, including biopsy of the right temporal artery,
      remained non-specific for the disease. Our diagnosis was based on the unusual
      clinical presentation of the disease.

PMID- 11582955
TI  - Aberrant right subclavian artery (arteria lusoria) as a rare cause of dysphagia
      and dyspnea in a 79-year old women with right mediastinal and retrotracheal mass,
      and co-existing coronary artery disease.
AB  - A rare case of a 79-year old women with dysphagia and dyspnea secondary to
      compression of the esophagus by an aberrant right subclavian artery (ARSA, A.
      lusoria) is presented. This abnormality is generally silent and often an
      incidental x-ray finding. Computed tomography and intraarterial angiography,
      including direct catheterization of the ARSA, established the diagnosis. The
      interdependence with a co-existing coronary artery disease is discussed. Thus,
      ARSA has to be taken into account in patients with abnormal x-ray findings
      presenting with dysphagia and dyspnea.

PMID- 11582956
TI  - [Compression syndrome of the arteria circumflexa humeri posterior in a volleyball
      player].
AB  - The compression syndrome of the posterior circumflex humeral artery is an
      infrequent vascular compression syndrome and differential diagnosis of the
      thoracic outlet- and the hypothenar-hammer-syndrome. The diagnosis includes a
      complete interview and a transfemoral armarteriography. Our report is about an
      affected volleyball player, the possible pathomechanism that can lead to this
      syndrome and the current literature.

PMID- 11582957
TI  - Perspectives. Future retirees may get little employer help for health.

PMID- 11582958
TI  - [Anti-secretory agents modify the gastric localization of Helicobacter pylori].

PMID- 11582959
TI  - [Differential diagnosis of esophageal motor disorders based in characteristics of
      dysphagia].
AB  - BACKGROUND: Dysphagia is one of principal symptoms of esophageal disorders and
      its characterization is important for diagnosis and management of patients.
      Anamnesis is useful for differentiating organic and functional dysphagia, but
      data are lacking about dysphagia characterization among different motor
      disorders. OBJECTIVES: To evaluate if it is possible the distinction among
      esophageal motor disorders according to their manometric diagnosis, based on
      dysphagia characteristics. PATIENTS AND METHODS: Dysphagia characteristics
      (relation with bolus, frequency and localization) of 133 patients submitted to
      esophageal manometry were reviewed and analysed. All patients had barium swallow
      studies and/or endoscopy in order to exclude organic lesions. RESULTS: Esophageal
      manometry was abnormal in 85% of the patients. Characteristics of dysphagia were
      compared among groups of patients with achalasia, esophageal spastic disorders,
      non-specific esophageal motor disorders and with normal test. The precise
      distinction among groups based solely on characteristics of dysphagia was not
      possible, however some aspects could point to one or another group. In achalasia
      patients, dysphagia for both solid food and liquids, constant and felt in
      substernal area, was more frequent in relation to every other group. Intermittent
      dysphagia was more frequent in patients with spastic disorders. Characteristics
      of dysphagia in patients with non-specific esophageal motor disorders were
      similar to those observed in the group with normal test, frequently referred in
      the neck. CONCLUSION: Characteristics of dysphagia were ancillary to presume the
      diagnosis of these motor disturbances, however esophageal manometry is necessary
      for the correct diagnosis in patients with functional dysphagia.

PMID- 11582960
TI  - [Hepatosplenic schistosomiasis portal hypertension: effect of esophagogastric
      devascularization with splenectomy on the diameter and mean flow velocity in the
      portal system (ultra-sonographic Doppler].
AB  - BACKGROUND: Esophagogastric devascularization with splenectomy has been used for
      the treatment of upper digestive bleeding due to esophagic varices in
      hepatoportal mansoni's schistosomic portal hypertension. Nevertheless, early
      portal thrombosis has hampered this surgical technique (13.3% and 53.2%),
      compromising the good results on the hemorrhagic side. Supposing that portal
      circulatory changes, due to the surgical treatment, may play an important role in
      this kind of complication, our objective was to identify the hemodynamic
      facilitating factors. Portal hemodynamic aspects, identified by ultra-sonographic
      Doppler study, from two groups of patients: non-operated upon and splenectomized
      with esophagogastric devascularization in late post-operatory phase (in excess of
      6 moths), with portal hypertension due to mansoni hepatoesplenic portal
      hypertension and in similar clinical conditions, were compared. METHOD: Fifty
      eight ambulatorial patients were studied, all had portal hypertension caused by
      mansoni's hepatosplenic schistosomiasis and previous bouts of digestive bleeding.
      They were divided in two groups: A--29 followed clinically/endoscopically, and
      group B--29 previously submitted to esophagogastric devascularization with
      splenectomy. In all was measured the diameter and mean flow velocity in the
      portal vein and its right and left branches by ultra-sonographic Doppler study.
      The results were submitted to statistical analysis for inter- and intra-group
      comparison. RESULTS: Group A (non-operated): the portal vein diameter was greater
      than the right and left branches (10.6 +/- 2.9, 8.0 +/- 1.8, 9.1 +/- 2.6 cm), the
      mean flow velocities in the portal vein and its branches were similar (15.62 +/-
      6.17, 14.92 +/- 5.33, 16.12 +/- 4.18 cm/seg). Group B (operated): the diameter
      and mean flow velocity in all vessels were reduced (8.8 +/- 1.7, 5.2 +/- 1.2, 7.5
      +/- 2.2 cm/12.53 +/- 2.60, 8.86 +/- 1.75, 9.69 +/- 3.75 cm/seg). CONCLUSIONS:
      After esophagogastric devascularization with splenectomy, there was a reduction
      of the diameter and mean flow velocity in the portal vein, its right and left
      branches.

PMID- 11582961
TI  - [Antibodies to hepatitis C virus in patients undergoing hemodialysis in Salvador,
      BA, Brazil].
AB  - BACKGROUND: Hepatitis C infection in hemodialysis units has been evaluated in
      different geographic regions. AIMS: The prevalence of anti-HCV in patients
      undergoing hemodialysis program in the city of Salvador, State of Bahia, Brazil,
      was studied and its association with transfusions, duration of hemodialysis and
      ALT elevation. METHOD: During a period of 17 months, all patients undergoing
      dialytic treatment, were evaluated. The total number of patients was 395, all of
      whom completed a questionnaire and provided serum samples for laboratory
      analysis. Serological levels were measured for ALT and the samples were tested
      for anti-HCV using ELISA II with a further confirmation using RIBA III. RESULTS:
      Anti-HCV was positive in 23.8% (94/395). The presence of transfusions was
      associated with anti-HCV and as the number of transfusions used increased, so did
      the frequency of anti-HCV. Of the patients who never received transfusions, 12.5%
      (6/48) were anti-HCV positive. The duration of dialytic treatment lasted from
      53.44 +/- 36.45 months in the anti-HCV positive group and 22.10 +/- 22.75 months
      for the group testing negative. ALT elevation was more frequent in the anti-HCV
      positive group. Positivity for the RIBA III fractions was 79.8%, 100%, 80.9% and
      52.1%, for c100-3, c33, c22 and NS5, respectively. The anti-NS5 was even less
      frequent in the group with elevated ALT. CONCLUSIONS: The prevalence of anti-HCV
      in patients undergoing chronic hemodialysis in Salvador, Bahia, is elevated and
      it is associated with transfusions, a longer duration of dialytic treatment and
      ALT elevation.

PMID- 11582962
TI  - Videolaparoscopic cholecystectomy. Analysis of the clinical and functional
      aspects of mechanical lifting of the abdominal wall.
AB  - BACKGROUND: Mechanical lifting of the abdominal wall, a method based on traction
      and consequent elevation of the abdominal wall, is an alternative procedure to
      create enough intra-abdominal space necessary for videolaparoscopic surgery,
      dispensing the need for intraperitoneal gas insufflation. OBJECTIVE: This study
      aims to evaluate the technical feasibility of this procedure to carry out a
      videolaparoscopic cholecystectomy, while analyzing the clinical and functional
      aspects of this technique. PATIENTS AND METHODS: In the Digestive Tract Surgery
      Discipline of the Medical School at the University of Sao Paulo, Sao Paulo, SP,
      Brazil, was created the equipment to perform videolaparoscopic surgery using this
      method. The equipment has two sections: an external part which consisted of a
      frame attached to the operating table, inside which there is a sliding steel
      cable, moved by a ratched which is located at the lower end of one of the frame
      rods; the internal rod, the support, has an "L" shape, and its horizontal branch
      is made up of three turning rods and which is connected to the steel cable after
      insertion into the abdominal cavity. Ten patients underwent videolaparoscopic
      cholecystectomy using this equipment. The time taken to install the equipment,
      the operating area characteristics, the interference from the lifting equipment
      on surgical movements and on the intra-operative cholangiography, the
      measurements made of the force used during traction and extension of the
      abdominal wall elevation, and the medication required for postoperative analgesia
      were all evaluated. RESULTS: There were no intra-operative complications, and in
      none of the cases was it found necessary to convert to open surgery. We
      considered the insertion a safe and uncomplicated procedure, and the traction
      system efficient. Apart from the elevation of the abdominal wall, the
      distribution of the viscera inside the abdominal cavity is fundamental for the
      operating area. Depending on the position of the epigastric trocar, the lifting
      equipment can interfere with the surgical instruments mobility. It may be
      necessary to reposition the support to perform the intra-operative
      cholangiography. The tensional force applied to the peritoneal surface by the
      lifting rods is small, and no additional postoperative pain was observed using
      this procedure. CONCLUSION: These results show that using the equipment described
      in this study, mechanical lifting of the abdominal wall is a feasible alternative
      for undertaking videolaparoscopic cholecystectomy.

PMID- 11582963
TI  - [Influence of ascorbic acid on anastomosis and in jejunal loop in rat].
AB  - BACKGROUND: The effects of vitamin C on anastomotic healing process are
      controversial. OBJECTIVE: To compare the jejunal anastomotic tension and in the
      upright segment in different postoperative periods. METHOD: Fifty male rats
      weighing 250 to 400 grams were submitted to laparotomy. The jejunum was
      transversally cut 10 cm from the duodenojejunal flexure, and subsequently
      anastomosed. The rats were divided into two groups (n = 25). Group I--control,
      Group II--oral administration of vitamin C (100 mg/kg). The anastomotic and the
      upright segment resistance was determined by using bursting pressure test on the
      3rd, 5th, 7th, 21st and 28th postoperative days. RESULTS: The rats submitted to
      oral administration of ascorbic acid show higher bursting pressure on the 5th,
      7th and 28th postoperative days. The bursting resistances of the upright segment
      was higher on the rats submitted to vitamin C ingestion. CONCLUSIONS: Vitamin C
      enhances the anastomotic and jejunal resistances. Moreover, the final resistance
      on the upright jejunal segment was significant higher than in the control group.

PMID- 11582964
TI  - [Acute pancreatitis due to intramural hematoma of the duodenum by the use of
      anticoagulants].
AB  - BACKGROUND: Spontaneous intramural hemorrhage of the duodenum due to
      anticoagulant therapy is rare and the treatment is controversial. OBJECTIVE: To
      present the acquired knowledge with the treatment of these disease. CASE REPORT:
      A 71-year-old women receiving for a 3 month period an anticoagulant therapy
      presented cervical bleeding of soft tissues and symptoms of acute pancreatitis
      and high small bowel obstruction. Early noninvasive diagnosis by computed
      tomographic scan was possible and conservative therapy proved successful in
      complete resolution of the pancreatitis and obstructive symptoms, with resumption
      of oral intake in the fourth day of treatment. The frequency of bleeding in high
      risk patients during warfarin therapy is reduced by less intense therapy,
      achieving a prothrombin time with an International Normalized Ratio of 2.0 to
      3.0. RESULTS: The use of conservative treatment was helpful and the patient was
      discharged asymptomatic, 10 days after admission. CONCLUSION: It is suggested
      conservative treatment for intramural hematoma of the duodenum and recommended
      laparotomy only when complications occur.

PMID- 11582965
TI  - Diagnosis of alpha-1-antitrypsin deficiency by DNA analysis of children with
      liver disease.
AB  - BACKGROUND: Alpha-1-antitrypsin deficiency is a genetic disorder which is
      transmitted in a co-dominant, autosomal form. Alpha-1-antitrypsin deficiency
      affects mainly the lungs and the liver leading, in the latter case, to neonatal
      cholestasis, chronic hepatitis or cirrhosis. A precise diagnosis of Alpha-1
      antitrypsin deficiency may be obtained by biochemical or molecular analysis.
      OBJECTIVE: The purpose of this study was to use DNA analysis to examine the
      presence of an alpha-1-antitrypsin deficiency in 12 children suspected of having
      this deficiency and who showed laboratory and clinical characteristics of the
      disease. PATIENTS AND METHODS: Twelve patients, aged 3 months to 19 years, who
      had serum alpha-1-antitrypsin levels lower than normal and/or had hepatic disease
      of undefined etiology were studied. The mutant alleles S and Z of the alpha-1
      antitrypsin gene were investigated in the 12 children. Alpha-1-antitrypsin gene
      organization was analyzed by amplification of genome through the polymerase chain
      reaction and digestion with the restriction enzymes Xmnl (S allele) and Taq-1 (Z
      allele). RESULTS: Seven of the 12 patients had chronic liver disease of undefined
      etiology and the other five patients had low serum levels of alpha-1-antitrypsin
      as well as a diagnosis of neonatal cholestasis and/or chronic liver disease of
      undefined etiology. Five of the 12 patients were homozygous for the Z allele (ZZ)
      and two had the S allele with another allele (*S) different from Z. CONCLUSION:
      These results show that alpha-1-antitrypsin deficiency is relatively frequent in
      children with chronic hepatic disease of undefined etiology and/or low alpha-1
      antitrypsin levels (41.6%). A correct diagnosis is important for effective
      clinical follow-up and for genetic counseling.

PMID- 11582966
TI  - [Squamous cell carcinoma of the canal anal].
AB  - BACKGROUND: Anal cancer is an uncommon malignancy accounting for only a small
      (4%) percentage of intestinal cancer. The authors described the clinical aspects
      and the treatment of the patients with squamous cell carcinoma of the canal anal.
      PATIENTS: Eleven patients with squamous cell carcinoma treated among 1995 and
      1999, were analyzed retrospectively. Nine were women and two were men. The mean
      age was 57.6 years old (range 35-82 years old). RESULTS: The most common symptoms
      were rectal bleeding, local tumor and pain. Six of them had previous anal benign
      disease and two had metastases at the diagnosis. All were submitted to systemic
      chemotherapy with 5-fluorouracil and mitomycin and radiotherapy with 4500 cGy.
      Four patients had residual disease after chemo radiation and salvage surgery with
      abdominoperineal resection was done. Three patients had recurrence and four died
      from the disease. CONCLUSION: Most of our patients were women. The chemo
      radiation can be a curable treatment in patients with local disease; conversely
      in patients with residual disease, abdominoperineal resection must be done.
      Although anal cancer is an often curable disease, four patients died because the
      diagnosis was done in advanced stage.

PMID- 11582967
TI  - Limitations of MMSE when screening for dementia.

PMID- 11582968
TI  - Short-term use of botanicals may be beneficial for women with menopausal
      symptoms.

PMID- 11582969
TI  - ARBs provide renal protection in type 2 diabetes.

PMID- 11582970
TI  - Fragile skin. Exposure to the sun makes skin of an alcoholic patient susceptible
      to traumatic injuries.

PMID- 11582971
TI  - Cholesterol 2001. Rationale for lipid-lowering in older patients with or without
      CAD.
AB  - Statin treatment of men and women age > or = 50 with coronary artery disease
      (CAD) and hypercholesterolemia reduces the risk of all-cause mortality,
      cardiovascular mortality, coronary events, coronary revascularization, stroke,
      and intermittent claudication. The target serum low-density lipoprotein (LDL)
      cholesterol level is < 100 mg/dL in older patients with CAD, prior stroke,
      peripheral arterial disease, or extracranial carotid arterial disease and serum
      LDL cholesterol > 125 mg/dL despite diet therapy. Statins are also effective in
      reducing cardiovascular events in older persons with hypercholesterolemia but
      without cardiovascular disease. Consider using statins in patients age 50 to 80
      without cardiovascular disease, serum LDL cholesterol > 130 mg/dL, and serum high
      density lipoprotein (HDL) cholesterol < 50 mg/dL.

PMID- 11582972
TI  - Prevention for the older woman. A practical guide to hormone replacement therapy
      and urogynecologic health.
AB  - Decisions to begin or continue hormone replacement therapy (HRT) are
      individualized, depending on a woman's anticipated benefits and risks from HRT.
      Estrogen, especially when begun early in menopause, has been shown to be
      beneficial in the prevention and treatment of osteoporosis. Potential risks of
      HRT include gallbladder disease, thromboembolism, and breast cancer. Systemic or
      topical estrogen can improve postmenopausal vaginal atrophy, vasomotor symptoms,
      and cervical cytologic changes. Treatment of other urogynecologic changes, such
      as vulval dystrophy and urinary incontinence, can relieve symptoms and improve
      the older woman's quality of life.

PMID- 11582973
TI  - Infectious disease. Update on treatment of pneumonia, influenza, and urinary
      tract infections.
AB  - Older persons are at increased risk for infection because of decreased
      physiologic reserves, acute and chronic comorbidities, time spent in hospitals or
      nursing homes, and high exposure to invasive procedures in those settings.
      Management of infection in older persons is complicated by several factors,
      including microbial resistance and the infrequency or absence of common infection
      signs and symptoms. Among the most common infections in older populations are
      community-acquired pneumonia, influenza, and urinary tract infection. Vigilance,
      early diagnosis, and strategic use of antibacterial or antiviral agents are key
      to effective patient management.

PMID- 11582974
TI  - CABG complication: subclavian artery steal syndrome increases risk of ischemia,
      death.

PMID- 11582975
TI  - Cholinesterase inhibitors. Comparing the options for mild-to-moderate dementia.
AB  - Cholinesterase inhibitors can be used as one element of a comprehensive approach
      to management of mild-to-moderate AD. Benefits include modest cognitive
      improvement, increased activation, and improved mood and behavior. Patients with
      other disorders, such as Lewy-body dementia, may also improve. The most common
      side effects include GI disturbances, insomnia, dizziness, fatigue, and muscle
      cramps. Adverse effects can be significantly reduced by waiting 4 to 6 weeks
      before increasing doses. Insomnia may be alleviated by having the patient take
      the medication early in the day.

PMID- 11582976
TI  - Medicare's role in financing allied health clinical training.

PMID- 11582977
TI  - National estimates of physician assistant productivity.
AB  - Analysis of productivity data from a nationally representative sample of
      physician assistants (PAs) showed that PAs performed 61.4 outpatient visits per
      week compared with 74.2 visits performed by physicians, for an overall physician
      full-time equivalent (FTE) estimate of 0.83. However, productivity of PAs varies
      strongly across practice specialty and location, with generalist PAs performing
      more visits than their specialist counterparts. Rural PA productivity is higher
      than urban productivity because of the concentration of generalist PAs in rural
      settings. A generalist PA physician FTE estimate of 0.75 appears to be more
      accurate than the 0.5 currently under consideration in proposed modifications to
      Health Personnel Shortage Area designation regulations.

PMID- 11582978
TI  - Autonomous ambulatory care by nurse practitioners and physician assistants in
      office-based settings.
AB  - Data from the 1997 National Ambulatory Medical Care Survey were used to examine
      the autonomous provision of ambulatory medical care by nurse practitioners (NPs)
      and physician assistants (PAs) in physician-managed office-based settings. An
      estimated 6.81 million office visits involved autonomous care by NPs and PAs, for
      an overall rate of 2.55 visits per 100 persons. The visit rates were greatest for
      patients over 64 years of age, females, blacks, and patients from the Northeast.
      The visits encompassed a broad range of acute and chronic problems, with a
      greater proportion of non-illness care visits when compared with visits to
      physicians. While NPs and PAs provided diagnostic services and pharmacotherapy,
      there was more emphasis on therapeutic or preventive services in their practices
      than among physicians' practices. Predisposing, enabling, and need factors were
      differentially associated with visits to NPs and PAs. Utilization of NPs and PAs
      as autonomous providers in office-based settings appears limited. Public policy
      and educational initiatives can focus on predisposing, enabling, and need factors
      to increase access to autonomous practice of NPs and PAs in ambulatory care.

PMID- 11582979
TI  - Wagging the dog: an analysis of year 2000 workforce and education outcomes from
      recommendations of the 1995 Pew Commission report.
AB  - Over-production in the number of hospitals and health care workers has led to
      increased cost of medical care and inequities within the health care delivery
      system. An increase in managed care penetration within the market-place is
      believed to mandate dramatic changes in the way that health care is structured
      and delivered. The 1995 Pew Commission report projected major changes in health
      care organizations and health manpower through the effects of managed care and
      public regulation. This paper describes the outcomes to health delivery
      organizations and the health care workforce five years since the Pew Commission
      Report and discusses the belief that market forces are more effective mechanisms
      for addressing health care delivery and workforce requirements than public
      regulatory initiatives.

PMID- 11582980
TI  - Reflections on building community: a different perspective on academic-community
      partnerships using the integration matrix.
AB  - Implementation of interdisciplinary rehabilitation services and clinical training
      in community settings is a complex process. Documented methods for analyzing,
      evaluating and monitoring the process within federally funded grant projects are
      limited. This paper reports on the use of one proposed method, the Integration
      Matrix of Konrad, as a framework for formative assessment and analysis of project
      operations. Based upon ongoing experiences implementing a Health Resources and
      Services Administration (HRSA) funded clinical training program in a community
      setting, a revision of the Integration Matrix is proposed to better reflect a
      community-centered, pervasive communication approach to program operations and
      analysis.

PMID- 11582981
TI  - Development and conduct of clinical trials in allied health professions: the
      communication-disorders experience.

PMID- 11582982
TI  - Health science careers: tech prep consortium for New Jersey.

PMID- 11582983
TI  - Health professions education online: a case study.

PMID- 11582984
TI  - Economic modeling as a component of academic strategic planning.

PMID- 11582985
TI  - Interdisciplinary delivery of oral health care student-training components.
AB  - The purpose of this study was to identify the interdisciplinary nature of oral
      health care components within Area Health Education Centers (AHECs). A
      questionnaire was designed to elicit descriptive information from AHEC program
      directors. The questionnaire surveyed the entire population of 37 AHEC project
      directors identified by the National AHEC Program Office. A total of 23 of 37
      questionnaires were returned, for an overall response rate of 62%. Results
      indicate that dental and dental hygiene students are learning alongside other
      student health care professionals in an interdisciplinary environment. These oral
      health care components incorporate a variety of classroom delivery methods, such
      as problem-based learning, interdisciplinary learning, and reflective sessions.
      The survey also revealed numbers of students and programs involved in current
      interdisciplinary activities.

PMID- 11582986
TI  - [Traumatic extraparenchymal hemorrhage of the posterior cranial fossa as a
      warning sign of atlanto-axial instability].

PMID- 11582987
TI  - [A case of painful defect of unknown origin of the pediatric patella].
AB  - An uncertain history of potential trauma versus possible developmental variants
      and disorders in childhood may cause differential diagnostic problems in
      pediatric radiology. We report the case of a 12-year old boy with an unclear
      unilateral defect of the patella and long-persisting complaints in his knee. The
      plain radiological and MRI morphology of this lesion are described and possible
      differential diagnoses are discussed.

PMID- 11582988
TI  - [Effects of stereotaxic puncture biopsy on breast diagnosis in a general
      hospital].
AB  - PURPOSE: To inform about the experiences by introducing this method, concerning
      feasibility, indication, procedure, histologic analysis, changes in admission of
      patients, consequences for the diagnostic work-up of breast lesions. MATERIAL AND
      METHODS: In 80 patients, 84 lesions were biopsied. The patients were chosen
      according to the "Breast Imaging Reporting A Data System", recommended by the
      American College of Radiology, with slight modifications. The examinations were
      performed on a mammographic unit with a special equipment for stereotactic
      biopsy, using a biopsy gun. RESULTS: Histologic assessment was possible for all
      the cores provided. 12 of 84 lesions (14.3%) contained carcinoma, 53/84 (63.1%)
      mastopathic changes, 19/84 (22.6%) other benign findings. The percentage of out
      patients was constantly high with 55%, the number of gynecologic in-patients
      increased slightly from 24 to 27%. The number of open biopsies decreased from 9
      to 6 per month with a considerable decrease (30%) of negative biopsies.
      CONCLUSIONS: Co-operation with the admitting physicians, who are also doing
      mammography, should set a new course towards stereotactic core breast biopsy
      already before the patients are admitted to the hospital. An increasing
      acceptance by the gynecologists doing open biopsies could lead to a further
      decrease of unnecessary operations. The effect by direct histologic feedback
      improves the quality of mammographic diagnostic.

PMID- 11582989
TI  - [Diagnosis of rare diseases of the popliteal artery].

PMID- 11582991
TI  - Recurrent hyperparathyroidism after total parathyroidectomy due to multiple
      ectopic parathyroid glands in a patient with long-term haemodialysis.
AB  - We report the rare case of a recurrent hyperparathyroidism after total
      parathyreoidectomy due to multiple ectopic glands in a patient on long-term
      haemodialysis. In a today 47 years old man with membranoproliferative
      glomerulonephritis intermittent haemodialysis therapy was started in 1975. In
      1982 an advanced secondary hyperparathyroidism with a parathormone (PTH) level >
      500 pg/l was diagnosed; later on PTH concentration increased to 2,550 pg/ml. In
      1987 total parathyroidectomy with parathyroid autograft into the left forearm was
      performed. After parathyroidectomy the PTH level fell to 150 pg/ml. In 1993 PTH
      concentration increased again to 1,750 pg/ml. There was no evidence for recurrent
      parathyroid glands in the neck or forearm. Therefore, we investigated the
      substernal region by 99mTc-tetrofosmin scintigraphy and magnetic resonance
      imaging. Both investigations showed evidence for two ectopic parathyroid glands
      in the anterior mediastinum. In June 1999 in an open thoracic surgical procedure
      only the greater parathyroid gland in the anterior mediastinum was isolated, but
      a second gland was detected in the posterior mediastinum. Both parathyroid glands
      were resected (histologically hyperplastic parathyroid gland tissue). After
      surgery the PTH level decreased to 340 pg/ml, but later on PTH increased again to
      > 1,000 pg/ml in January 2001. A control 99mTc-tetrofosmin scan showed evidence
      for a third ectopic parathyroid gland in the anterior mediastinum. Recurrent
      secondary hyperparathyroidism can rarely be caused by recurrent ectopic
      parathyroid glands in the mediastinum.

PMID- 11582990
TI  - [Preoperative assessment of thyroid nodules in an endemic goiter region-
      possibilities and limitations].
AB  - In iodine-sufficient areas any thyroid nodule has to be regarded as potentially
      malignant, whereas in iodine-deficient areas (endemic goiter areas) thyroid
      nodules, even multinodular goiter, are frequent. The majority of thyroid nodules
      in an endemic goiter area can be regarded as being most likely benign and thus
      not all patients with multinodular goiter have to undergo surgery. The major
      diagnostic aim and challenge is the selection for surgery of only those patients
      who suffer from mechanical obstruction due to large goiter and those who present
      with nodules suspicious of malignancy. Thus, for these cases the question of
      accurately excluding or verifying malignancy is essential for the patient and the
      specialist of nuclear medicine or endocrinology. A variety of investigations may
      be used for the preoperative evaluation of thyroid nodules, although currently
      sonography and fine-needle biopsy have to be regarded as the key investigations
      to clarify preoperatively the dignity of thyroid nodules. The article presents
      the indications and limitations of the different methods in use for the
      evaluation of thyroid malignancy. The authors present a diagnostic algorithm for
      the preoperative evaluation of thyroid malignancy with special respect to
      problems occurring in a(n) (former) endemic goiter area.

PMID- 11582992
TI  - [Xenotransplantation of islets of Langerhans: a possible therapy for diabetes
      mellitus?].
AB  - The current therapy of insulin-dependent (Type 1) diabetes mellitus is based on
      the lifelong application of exogenous insulin. Since the destruction of insulin
      producing pancreatic islets is considered to be responsible for disease
      development, the transplantation of healthy islets could turn out to be the
      curative therapy of the disease. Unfortunately, numerous problems seem to be
      associated with the transplantation of islets of human origin. Therefore,
      xenotransplantation (the transplantation of organs/tissues of animal origin)
      could turn out to be an effective alternative treatment protocol. Some human
      trials have already been performed. In this brief review the author attempts to
      make a synopsis of the present perspectives and problems of islet
      xenotransplantation.

PMID- 11582993
TI  - [Paget disease or fibrous dysplasia of the radius?--A case report].
AB  - A 46 years old man, who showed a painful and progressive deformity of the left
      radius, is presented. After some months a fracture within the affected bone area
      occurred. The diagnostic procedures including X-ray, MRI, scintigraphy and
      histology were controversial. Both fibrous dysplasia and Paget's disease of bone
      were suspected. The critical analysis of all results concluded that the most
      likely diagnosis was fibrous dysplasia. Unaware of the diagnostic discrepancies,
      the patient received a therapy with pamidronate 3 x 60 mg intravenously, which
      improved symptoms. After 14 months, the patient complained again about pain in
      the left radius. After a second therapy with pamidronate the patient currently
      exhibits no symptoms. The controversial diagnostic results and the applied
      therapeutic procedure are discussed.

PMID- 11582994
TI  - [Healing peptic ulcer disease with therapy of Helicobacter pylori infection--an
      overview].
AB  - Over the last 15 years several new aspects in the pathogenesis and basic changes
      in therapeutic strategies for healing of peptic ulcers have been introduced. The
      discovery of Helicobacter pylori, the possibility of treatment of the infection
      and consecutive healing of peptic ulcer disease have changed the understanding of
      the pathophysiology of the peptic ulcer disease. Most gastric or duodenal ulcers
      are based on Helicobacter pylori infection. Newer therapeutic strategies to cure
      Helicobacter pylori infection consist of proton pump inhibitor (PPI) based triple
      therapy, containing in addition two antibiotics chosen from clarithromycin,
      amoxicillin and metronidazole, administered over 7 days. The other main cause of
      gastroduodenal ulcers are non-steroidal antirheumatic drugs or aspirin intake.
      PPI are therapeutic strategies of choice for treatment of such lesions. Main
      topics of this overview are the principles and the therapeutic proceeding in the
      management of Helicobacter pylori-associated peptic ulcer disease. The
      differences between duodenal and gastric ulcer are especially dealt with.

PMID- 11582995
TI  - [Applied medicine in the field of specialties and control of professional
      theoretical research].
AB  - There are many cases in every medical specialty in which it is impossible to make
      exact diagnoses. Coping optimally with these health disturbances will only be
      possible if occupational-theoretical basic research of applied medicine has been
      done. Ways are shown how to reach this goal.

PMID- 11582996
TI  - [3-dimensional models of actual or simulated cesarean sections].
AB  - Following upon an etymological and historical introduction, this report refers to
      two three-dimensional wax models of Caesarean sections, which have recently been
      acquired by the Pathological-anatomical Federal Museum in Vienna. Information is
      given on origin, dating and kind of production; questions of indication and
      operation technique, and--when in doubt--obduction technique, are being
      considered.

PMID- 11582997
TI  - [Healing and helping in Hallstatt--on the medical history of mining town in
      Salzkammergut].
AB  - The medical care practiced at Hallstatt was specifically influenced by its salt
      mine, well known since prehistoric times, and by the isolated location of this
      place lying on a lake as well as in the mountains. Since the 16th century the
      Hallstatt saltworks had a hospital, with a special isolation ward since 1772. In
      addition to it, a small hospital for infectious diseases was opened at the
      beginning of the 20th century. The barber-surgeons, whose names have been known
      since the 17th century, and later on the university-graduated doctors had to do
      their work without any outside help and moreover, they had to supply their
      patients with necessary medicaments. In her own house, the last local midwife
      used to offer delivery and lying-in rooms for women. The mine rescue service
      (since 1945), the mountain rescue service (since 1923), the water rescue service
      (since 1960) and the Red Cross (since 1978) have been playing an important part
      preparing the work of the local doctors. Paleoparasitological examinations of
      human excrements found in collapsed prehistoric tunnels proved that the miners
      had suffered from whip worms and eel worms. Contrary to the badly preserved
      skeletons found in the prehistoric burying place on the Hallstatt Salzberg, the
      human remains in the Hallstatt charnel house made anthropological examination
      possible.

PMID- 11582998
TI  - [Therapy of tic disorders apparently of organic origin in a multi-morbid 5-year
      old patient with lofexidine (Britlofex) and clonidine (Catapressan)].
AB  - We report about a five year-old patient suffering from tics and ADHD (attention
      deficit hyperkinetic disorder), aggressions, depression and emotional disorder.
      Furthermore, an epileptic focus and perinatal encephalopathy were diagnosed.
      Lofexidine (Britlofex) medication did not reduce Tic symptomatology, but showed
      remarkable sedative effects. Family therapy and Clonidine (Catapressan)
      medication reduced symptomatology significantly.

PMID- 11582999
TI  - Cumulative indexes, volumes 51-75, 1996-2000.

PMID- 11583000
TI  - Impact of human aging on energy and protein metabolism and requirements.
      Proceedings of an IDECG workshop. Boston, Massachusetts, USA. May 3-6, 1999.

PMID- 11583001
TI  - Panel Discussion. Millennium Festival of Medicine--Transfusion 2020--18 October
      2000.

PMID- 11583002
TI  - Patient/provider internet connectivity: leading the revolution of healthcare
      delivery.

PMID- 11583003
TI  - Proceedings from the International Society of Blood Transfusion VII European
      Congress. Paris, France, July 15-18, 2001.

PMID- 11583004
TI  - On-line and electronic CME.

PMID- 11583005
TI  - Into the jaguar's den.

PMID- 11583006
TI  - First operative series that documented and used posterior gastric fixation for
      the surgical correction of hiatus hernia and gastroesophageal reflux.

PMID- 11583007
TI  - Susceptibilities of Propionibacterium acnes ophthalmic isolates to moxifloxacin.

PMID- 11583008
TI  - Plasmid-mediated rifampin resistance encoded by an arr-2-like gene cassette in
      Klebsiella pneumoniae producing an ACC-1 class C beta-lactamase.

PMID- 11583010
TI  - Proceedings of the 7th Annual Cardiothoracic Techniques and Technologies Meeting.
      Current Trends in Thoracic Surgery VII. New Orleans, Louisiana, USA. January 24
      27, 2001.

PMID- 11583009
TI  - Interspecies transfer of antibiotic resistance between Helicobacter pylori and
      Helicobacter acinonychis.

PMID- 11583011
TI  - Safe design and use of self-contained wet source storage gamma irradiators
      (category III). American National Standard.

PMID- 11583012
TI  - [35th Meeting of the German-Speaking Society of Mycology. Marburg, Germany,
      September 13-15, 2001. Abstracts].

PMID- 11583013
TI  - Are technologists qualified to be educators? Counterpoint: technologists are
      qualified to be educators.

PMID- 11583014
TI  - Pitfalls in assessing the quality of care for patients with cardiovascular
      disease.
AB  - PURPOSE: There are no clinical performance measures for cardiovascular diseases
      that span the continuum of hospital through postdischarge ambulatory care. We
      tested the feasibility of developing and implementing such measures for patients
      with acute myocardial infarction, congestive heart failure, or hypertension.
      SUBJECTS AND METHODS: After reviewing practice guidelines and the medical
      literature, we developed potential measures related to therapy, diagnostic
      evaluation, and communication. We tested the feasibility of implementing the
      selected measures for 518 patients with myocardial infarction, 396 with heart
      failure, and 601 with hypertension who were enrolled in four major U.S. managed
      care plans at six geographic sites, using data from administrative claims,
      medical records, and patient surveys. RESULTS: Difficulties in obtaining timely
      data and small numbers of cases adversely affected measurement. We encountered 6-
      to 12-month delays, disagreement between principal discharge diagnosis as coded
      in administrative and records data (for 9% of myocardial infarction and 21% of
      heart failure patients), missing medical records (20% for both myocardial
      infarction and heart failure patients), and problems in identifying physicians
      accountable for care. Low rates of performing key diagnostic tests (e.g.,
      ejection fraction) excluded many cases from measures of appropriate therapy that
      were conditional on test results. Patient survey response rates were low.
      CONCLUSIONS: Constructing meaningful clinical performance measures is
      straightforward, but implementing them on a large scale will require improved
      data systems. Lack of standardized data captured at the point of clinical care
      and low rates of eligibility for key measures hamper measurement of quality of
      care.

PMID- 11583016
TI  - Spontaneous rupture of the malarial spleen.

PMID- 11583015
TI  - Remission of a high-grade gastric mucosa associated lymphoid tissue (MALT)
      lymphoma following Helicobacter pylori eradication and highly active
      antiretroviral therapy in a patient with AIDS.

PMID- 11583017
TI  - Seasonal control of warfarin therapy.

PMID- 11583018
TI  - Selenoproteins in human thyroid tissues.
AB  - The aim of the present work was to clarify whether the activities of
      selenoenzymes can serve as markers for different tumors or goiters, as classified
      by histological criteria. The following parameters were determined: 1) selenium
      content of plasma (Se), 2) activities of the selenoenzymes: plasma glutathione
      peroxidase (plGSHPx), cytosolic glutathione peroxidase (cGSHPx), type I and type
      II iodothyronine deiodinases (ID-I, ID-II), thioredoxin reductase (THRR) in human
      thyroid tissues. The material came from follicular neoplasm, papillary carcinoma,
      struma nodosa, struma lymphomatosis Hashimoto, other thyroid surgery specimens,
      and normal tissues. There was no difference in Se nor in plGSHPx between patients
      and healthy volunteers. No significant differences were found for any parameter
      in thyroid carcinoma versus normal or goitrous thyroid tissue. In the whole group
      of thyroid surgery specimens the statistically significant correlations were
      found between ID-I and ID-II and between THRR and selenoperoxidases. Principal
      components analysis confirmed the above correlation and moreover revealed
      correlation between Se and plGSHPx, but did not detect any clear distinction
      between patients with the different diagnoses.

PMID- 11583019
TI  - Influence of plasma glutathione levels on radiation mucositis.
AB  - PURPOSE: To test the hypothesis that there is a link between plasma glutathione
      (GSH) or other antioxidants (uric acid, ascorbate) and the severity of radiation
      mucositis following radiation treatment of tumors of the head and neck. PATIENTS
      AND METHODS: Patients with carcinomas of the head-and-neck region were treated
      with the continuous hyperfractionated accelerated radiotherapy (CHART) regimen
      (54 Gy in 36 fractions over 12 days). Samples of blood plasma were analyzed for
      GSH, cysteine, urate, and ascorbate by high-pressure liquid chromatography.
      Patients were graded for dysphagia and requirement for analgesics. The areas
      under the curves of scores over 2-6 weeks following treatment were computed, and
      Spearman's rank-correlation coefficient was used to test for an association
      between plasma GSH levels (or those of other antioxidants) and mucositis.
      RESULTS: The pretreatment plasma GSH level in 18 patients scored in the study was
      1.0 +/- 0.7 M. Analysis of these and the dysphagia scores produced a correlation
      coefficient of 0.22 (confidence interval -0.28, 0.61; p = 0.39). No correlation
      was seen between mucositis severity and other measures of plasma antioxidants:
      cysteine (7.6 +/- 1.7 M), cysteine + GSH (8.6 +/- 1.9 M), uric acid (317 +/- 86
      M), ascorbate (29 +/- 20 M), or whole-blood GSH concentrations (1,010 +/- 239 M).
      CONCLUSION: The measurements of approximately micromolar levels of plasma GSH, or
      about 10 M cysteine + GSH (almost all of the total nonprotein thiols), are
      consistent with most other published data for either healthy adults or cancer
      patients; however, the values reported in an earlier study, suggesting a link
      between GSH and mucositis, are much higher. The hypothesis of a possible link
      between radiation mucositis and plasma-free (nonprotein) thiols was not
      supported.

PMID- 11583020
TI  - North American Association for the Study of Obesity annual meeting. October 7-10,
      2001. Quebec City, Canada. Abstracts.

PMID- 11583021
TI  - 9th World Congress of Pediatric Dermatology. Cancun, Mexico, October 20-24, 2001.
      Abstracts.

PMID- 11583022
TI  - Society for Psychophysiological Research 41st annual meeting. October 10-14,
      2001. Montreal, Canada. Abstracts.

PMID- 11583023
TI  - fMLP-induced respiratory burst and the intracellular Ca2+ signal are not
      interrelated in neutrophils.
AB  - Reactive oxygen intermediate (ROI) production and the development of the
      intracellular (IC) Ca2+ ([Ca2+]i) signal by formyl-Met-Leu-Phe (fMLP) stimuli
      were investigated in neutrophils. When the concentration was varied between 2.3
      nM-2.3 microM, ROI production and the [Ca2+]i signal showed different fMLP
      concentration dependencies. ROI production increased continuously with increasing
      fMLP concentrations, while the [Ca2+]i signal responses reached a plateau around
      230 nM fMLP. Moreover, when a consecutive, 2.3 microM fMLP stimulus was applied
      10 min after the first fMLP stimulus, the intensity of the ROI production and
      that of the [Ca2+]i signal showed a variable dependence on the fMLP concentration
      of the first stimulus. An initial fMLP dose of 2.3 nM and 23 nM sensitized the
      cells regarding their ROI production and [Ca2+]i signals. After a first fMLP
      stimulus of 230 nM, the second stimulus produced an increased [Ca2+]i signal,
      while no ROI production could be activated. A strong fMLP stimulus of 2.3 microM
      desensitized the cells regarding both [Ca2+]i signal and ROI production. However,
      even in these desensitized cells, a high level of ROI production could be evoked
      by other stimuli like PMA or opsonized zymosan. The differences observed between
      the fMLP concentration dependence of ROI production and the [Ca2+]i signal
      strongly suggest that these two phenomena are not interrelated.

PMID- 11583024
TI  - Unregulated activation of STAT-5, ERK1/2 and c-Fos may contribute to the
      phenotypic transformation from myelodysplastic syndrome to acute leukaemia.
AB  - Myelodysplastic syndrome (MDS) is characterised by ineffective erythropoiesis and
      poor progenitor response to erythropoietin (Epo). The aim of this study was to
      determine the role of the Epo-R mediated signalling in the rise of MDS and
      whether alteration of signalling pathways contribute to the leukeamogenesis from
      MDS to acute leukaemia. We analysed Epo and GM-CSF induced ERK1/2 activation, c
      Fos expression, STAT-5 and AP-1 DNA binding activities in mononuclear cells of
      umbilical cord blood (UCBMNC), normal marrow (NBMMNC) or marrow with MDS, AML
      with prior MDS and de novo AML. In UCBMNC and NBMMNC, Epo and GM-CSF induced the
      activation of STAT-5 DNA binding and ERK 1/2 activation (n = 6). In contrast, in
      MDS RA, both signalling pathways were activated only by GM-CSF but not by Epo (n
      = 7). In acute leukaemia, elevated basal activity of STAT-5 DNA binding appeared
      in 8/8 cases, which was independent of Epo or GM-CSF treatment. In normal and MDS
      samples, c-Fos and Egr-1 proteins were not detectable and the expression levels
      were not increased by Epo or GM-CSF treatment. In contrast, we found an elevated
      level of c-Fos expression in 5/8 acute leukemia cases, which was not further
      increased in the presence of Epo or GM-CSF. The elevated c-Fos expression was
      accompanied by an extremely high blast number in 5/5 cases. These results suggest
      that impaired ERK/MAPK activation, similarly to impaired STAT-5 activation in Epo
      R signalling, may be responsible for the apoptotic process and the block of
      maturation in MDS RA. The results also suggest that the appearance of the
      constitutively activated STAT-5 DNA binding and c-Fos expression may be used as a
      predictor of the blastic transformation.

PMID- 11583025
TI  - Effect of tresperimus on in vitro human cord blood CD34+ cell differentiation.
AB  - Tresperimus, an analogue of 15-deoxyspergualin (15-DSG), is immunosuppressive and
      prevents lethal graft-versus-host disease following allogeneic bone marrow
      transplantation in mice. Here, we present an in vitro dose response study
      examining the ability of tresperimus to support clonogenesis in cultured CD34+
      cord blood stem cells. Our findings revealed that only the lowest dose examined,
      0.5 microg tresperimus/ml, supports normal myelopoiesis, erythropoiesis and
      megakaryopoiesis. Greater concentrations of the drug induced dose-dependent
      inhibition of clonogenesis. This latter effect was not due to apoptosis and was
      reversible by drug withdrawal. We conclude that tresperimus at 0.5 microg/ml
      supports the clonogenic potential of cord blood CD34+ cells. Dose-dependent
      inhibition of clonogenesis was completely reversible following drug withdrawal.
      These results may be of clinical interest as tresperimus is currently used in
      phase I-III studies for the prevention of graft versus host disease in recipients
      of allogeneic bone marrow.

PMID- 11583026
TI  - Decrease in platelet serotonin level in uterine cervix cancer patients.
AB  - Platelet serotonin (5-HT) concentration was measured by HPLC with electrochemical
      detection in 46 women suffering from cancer of the uterine cervix and 16 matched
      controls. About 53% reduction (p < 0.05) was recorded in platelet 5-HT level in
      cancer patients against a control value of 1.29 +/- 0.16 (mean +/- S.E.) nmol per
      10(9) platelets. Depletion of intraplatelet 5-HT was positively correlated with
      clinical stage of the disease although a modest rise (p > 0.05) in platelet 5-HT
      was observed in patients at stage I. Serotonin release from platelets following
      activation with thrombin was considerably increased in cancer patients (38.2%
      compared to 17.4% in controls). The results demonstrate progressive depletion of
      intraplatelet 5-HT in cervical cancer patients. In addition, their platelets
      release more 5-HT than the controls upon activation by thrombin.

PMID- 11583027
TI  - Multiple myeloma in sickle cell syndromes.
AB  - Multiple myeloma (MM) is rare among patients with sickle cell syndromes (SCS). We
      describe six Greek sickle cell patients aged 56 to 65 years: five haemoglobin
      Sbeta+thalassaemia (HbSbeta+ (thal), one sickle cell anaemia (HbSS), who
      developed MM (three IgGkappa, one IgGlambda, one IgAkappa, and one IgGK-IgAK
      (biclonal). Our HbSbeta+thal cases, represent the first reported association of
      this entity with MM. Generalized bleeding diathesis, stroke, grand mal seizures,
      bone marrow necrosis and other clinical manifestations due to hyperviscosity
      aggravated by sickle cell vasoocclusion were treated by plasmaphereses and
      exchange blood transfusions. The increase of mean survival in SCS patients due to
      the current medical facilities may have an impact on the incidence of MM among
      them, if a pathogenetic link between the two conditions exists. All our patients
      carried a diagnosis of cholelithiasis which may predispose to MM; two of them
      progressed from a monoclonal gammopathy of undetermined significance (MGUS) to
      MM. Further studies are needed in order to understand the relationship between
      SCS and MM.

PMID- 11583028
TI  - Diffuse primary plasmacytoma of the lung.
AB  - Primary plasmacytoma of the lung is a rare tumor, thus presenting a diagnostic
      challenge to the clinician. So far, approximately 20 cases have been verified by
      immunohistochemistry. We describe an elderly patient presenting with progressive
      dyspnea on exertion, dry cough, weight loss and malaise. The main finding on
      plain chest radiography was a diffuse infiltration of pulmonary parenchyma in the
      lower parts of both lungs and in the middle part of the right lung. The histology
      of the open lung biopsy of the right middle lobe revealed massive and diffuse
      infiltration by well differentiated plasma cells with extracellular deposits of
      amyloid. The plasma cells and amyloid expressed a monoclonal lambda light chain.
      No monoclonal spike was shown by serum and urine immunoelectrophoresis. A
      skeletal survey and bone marrow biopsy specimen excluded a disseminated disease
      and a diagnosis of extramedullary plasmacytoma was made. The patient was
      considered for VI courses of VMCP chemotherapy after which a complete regression
      on chest roentgenography was evident. Almost five years after the diagnosis the
      patient is still alive without any evidence of disease recurrence or
      dissemination.

PMID- 11583029
TI  - Secondary myelofibrosis in visceral leishmaniasis--case report.
AB  - A 39-year-old woman with a history of travel to the Montenegrin coast presented
      with a 9-month long history of fever and weakness, and on examination was found
      to be emaciated with hepatosplenomegaly and pancytopenia. Marrow aspiration
      showed poor cellularity with abundant Leishman Donovan (LD) bodies in the
      macrophages. Bone marrow trephine biopsy revealed a marked myelofibrosis
      (Manoharan classification: grade III) with osteosclerosis. The impression smears
      of a trephine biopsy stained with Guiemsa also showed LD bodies. The patient did
      not exhibit evidence of any risk factors for visceral leishmaniasis (VL). She was
      treated with meglumine antimoniate (Glucantime) without any adverse effect. The
      spleen returned to a normal volume after 4 months and bone marrow trephine biopsy
      performed 6 months after initiation of the therapy had returned to normal. A
      diagnosis was difficult to establish as VL is rarely encountered in the
      continental parts of Yugoslavia, and with the presence of associated
      myelofibrosis it could easily have been mistaken for chronic idiopathic
      myelofibrosis. The association of myelofibrosis with visceral leishmaniasis has
      been reported in the literature only three times; we thus feel that documentation
      of this case is merited.

PMID- 11583030
TI  - Expression of KL-6 antigen on leukemia cells of a patient with chronic myelocytic
      leukemia in blastic phase.

PMID- 11583031
TI  - Elevation of serum procalcitonin level in a patient with chronic myelocytic
      leukemia.

PMID- 11583032
TI  - Detecting disseminated solid tumor cells in hematopoietic samples: methodological
      aspects.
AB  - Detection of tumor cell dissemination in solid tumor patients recently became
      essential to determine the prognosis of the disease and to monitor response to
      the therapy. Accurate detection of disseminated tumor cells in hematological
      samples requires tumor-specific target molecules, which allow sensitive and
      specific assays and, further, enable the quantification of tumor cells.
      Currently, numerous applications are in use, including immunological and
      molecular biological approaches. Theoretically, both ways are sensitive enough to
      detect less than one tumor cell in 1 million hematopoietic cells. With the
      improved sensitivity, however, the likelihood that unspecific events will be
      amplified is also increased. Moreover, biological and analytical variables may
      fundamentally influence the findings in a particular case. Basic methods,
      significant pitfalls and the most recent developments in this field are discussed
      in this overview.

PMID- 11583033
TI  - The Canadian Foundation for Dietetic Research dietetic research event. June 9,
      2001. Abstracts.

PMID- 11583034
TI  - Diabetes in the Americas.

PMID- 11583035
TI  - Tobacco use in the English-speaking Caribbean.

PMID- 11583036
TI  - The Global Youth Tobacco Survey: status of its implementation in Latin America
      and the Caribbean.

PMID- 11583037
TI  - Case definition. Acquired immunodeficiency syndrome (AIDS).

PMID- 11583038
TI  - Inequalities in infant mortality in the American region: basic elements for
      analysis.

PMID- 11583039
TI  - Ackee (Blighia sapida) poisoning in the Northern Province, Haiti, 2001.

PMID- 11583040
TI  - Understanding oblique impacts from experiments, observations, and modeling.
AB  - Natural impacts in which the projectile strikes the target vertically are
      virtually nonexistent. Nevertheless, our inherent drive to simplify nature often
      causes us to suppose most impacts are nearly vertical. Recent theoretical,
      observational, and experimental work is improving this situation, but even with
      the current wealth of studies on impact cratering, the effect of impact angle on
      the final crater is not well understood. Although craters' rims may appear
      circular down to low impact angles, the distribution of ejecta around the crater
      is more sensitive to the angle of impact and currently serves as the best guide
      to obliquity of impacts. Experimental studies established that crater dimensions
      depend only on the vertical component of the impact velocity. The shock wave
      generated by the impact weakens with decreasing impact angle. As a result,
      melting and vaporization depend on impact angle; however, these processes do not
      seem to depend on the vertical component of the velocity alone. Finally,
      obliquity influences the fate of the projectile: in particular, the amount and
      velocity of ricochet are a strong function of impact angle.

PMID- 11583041
TI  - Erosion of employer-sponsored health insurance coverage and quality.

PMID- 11583042
TI  - The future of Medicare.

PMID- 11583043
TI  - Improving the delivery and financing of developmental services for low-income
      young children.

PMID- 11583044
TI  - New approaches to academic health center affiliations: public hospitals and the
      Department of Veterans Affairs.

PMID- 11583045
TI  - Clinical outcomes of neonatal meningitis in very-low birth-weight infants.
AB  - We sought to describe the clinical presentation and consequences of meningitis
      among 64 very-low-birth-weight (VLBW <1.5 kg) infants who had 67 culture-proven
      episodes of meningitis over an 18-year period, 1977 through 1995. Demographic and
      neonatal descriptors of meningitis and later outcomes were retrospectively
      examined and neurodevelopmental outcomes of 39 of 45 (87%) meningitis survivors
      were compared to those of nonmeningitis survivors followed up to 20 months
      corrected age. Causes of meningitis included coagulase-negative Staphylococcus in
      43% of episodes, other gram-positive bacteria in 19%, gram-negative bacteria in
      17%, and Candida species in 20% of episodes. Spinal fluid abnormalities were
      sparse, regardless of etiologic organism. Of 38 nonbloody spinal fluid taps
      (<1,000 erythrocytes/mm3), 6 had >30 leukocytes/mm3, 5 protein >150 mg/dL%, and 6
      glucose <30 mg/dL (1.67 mmol/L). Only 10 infants (26%) had 1 or more of these
      spinal fluid abnormalities. Meningitis survivors had a higher rate of major
      neurologic abnormality (41% vs 11%, p<0.001) and subnormal (<70) Mental
      Development Index (38% vs 14%, p<0.001) than nonmeningitis survivors. Impairment
      rates did not differ by etiologic organism. The effect of meningitis on
      neurologic outcome persisted even after controlling for birth weight,
      intraventricular hemorrhage, chronic lung disease, and social risk factors (odds
      ratio 2.27 [95% CI 1.02, 5.05]). We conclude that despite a sparsity of abnormal
      spinal fluid findings, culture-proven neonatal meningitis among VLBW infants has
      a detrimental effect on neurologic outcome, which persists even after controlling
      for other risk factors.

PMID- 11583046
TI  - Prolonged bottle feeding in a cohort of children: does it affect caloric intake
      and dietary composition?
AB  - Little is known about the consequences to children of bottle feeding prolonged
      beyond age 1 year on caloric intake and overall dietary composition. To obtain
      these data, 165 children, followed up from infancy, were assessed in these
      respects for a 24-hour period at age 3 1/2 years. Bottle-fed children (n = 14)
      consumed more milk than their weaned counterparts (p < 0.001), had a higher mean
      daily calcium intake (p < 0.05), received fewer calories from carbohydrates (p =
      0.034), and received a greater percentage of calories from protein (p = 0.033).
      There were no significant differences between the groups in total caloric intake,
      total iron intake, total volume ofjuice, or calories from fat. Pediatricians
      questioned about the effects of continuing to offer children nutritive liquids
      from bottles as well as cups (versus offering cups alone) may inform parents that
      this feeding practice is associated with significantly greater milk consumption
      and daily calcium intake. However, this study could not find evidence that
      prolonged bottle feeding at age 3 1/2 years is associated with a significantly
      decreased total daily iron intake or an increased risk for factors associated
      with adiposity such as a greater daily calorie intake, a higher body mass index,
      or greater percentage of total calories derived from fat.

PMID- 11583047
TI  - Effect of RSV bronchiolitis practice guidelines on resource utilization.
AB  - We sought to determine whether institution of respiratory syncytial virus (RSV)
      practice guidelines decreased resource utilization for a heterogeneous population
      of children hospitalized with RSV bronchiolitis. Patients less than 24 months old
      with RSV bronchiolitis at a pediatric referral center were identified by
      retrospective chart review for consecutive RSV seasons. Before the guidelines
      were instituted patients were less likely to have a documented physician's
      assessment of response to albuterol, were more likely to have received
      supplemental oxygen and cardiorespiratory monitoring, and to be discharged on an
      albuterol regimen. Patients received more albuterol treatments. After the
      guidelines were in place fewer resources were utilized in the care of patients
      with RSV bronchiolitis. RSV practice guidelines may simplify and streamline the
      care of a heterogeneous population of children with bronchiolitis.

PMID- 11583048
TI  - Developmental screening of children diagnosed with congenital heart defects.
AB  - Children with congenital heart disease (CHD) are more likely than normal children
      to have developmental delays. The development of 64 children with CHD less than 6
      years old was screened with the Denver II. Thirty-five of the 64 children had CHD
      that required surgical or catheter intervention. These 35 children were
      significantly less likely than other children with CHD to be normal on
      developmental screening (46% vs 86%, respectively). Thirty-four percent of
      children with more severe CHD were referred for early intervention. As research
      shows the efficacy of early intervention, results indicate the need for early
      developmental evaluation of children with CHD of hemodynamic significance.

PMID- 11583049
TI  - Thrush in the breastfeeding dyad: results of a survey on diagnosis and treatment.
AB  - Infection with Candida albicans in the breastfeeding dyad has been associated
      with extreme pain in the breastfeeding mother and may lead to premature weaning.
      There is presently a dearth of information on diagnosis, natural history, and
      treatment of this condition in the literature. Therefore, before such a trial was
      conducted, a survey was sent to experts in the field of lactation, the members of
      The Academy of Breastfeeding Medicine, on the diagnosis and treatment of thrush
      in the breastfeeding mother and baby. Results showed that the majority of
      respondents relied primarily on history and physical examination of the baby, but
      not the mother, to make the diagnosis. Laboratory tests were ordered only rarely.
      The most common initial treatment was oral nystatin for the infant and cream for
      the mother's breasts. This was followed by oral nystatin for the infant and oral
      fluconazole for the mother. Treatment of recurrence or persistence was again most
      commonly nystatin for both mother and infant, followed by oral nystatin for the
      infant and oral fluconazole for the mother or oral fluconazole for both. In the
      absence of controlled trials of this condition, these results may serve as
      suggestions for the clinician, until definitive data are available.

PMID- 11583050
TI  - An infant with respiratory distress.

PMID- 11583051
TI  - Why diabetes camp?

PMID- 11583052
TI  - Pyruvate carboxylase deficiency. Report of a case and additional evidence for the
      "mild" phenotype.

PMID- 11583053
TI  - Three cases of penile edema in peripubescent males.

PMID- 11583054
TI  - Follow-up throat cultures.

PMID- 11583055
TI  - Substitutes for blood.

PMID- 11583056
TI  - Vagus nerve stimulation in depression.
AB  - Ever since the introduction of chemical and electrical convulsive treatment for
      psychiatric disorders in the 1930s and 1940s, biological techniques have been
      used extensively in the amelioration of a variety of psychiatric disorders.
      Techniques of recent vintage have included transcranial magnetic stimulation,
      deep brain stimulation and vagus nerve stimulation (VNS). Since VNS attenuates
      seizures in animal models, the treatment was initially developed and approved by
      the FDA for treatment of drug-resistant partial-onset epilepsy. Additional data,
      including the known neuroanatomy of the vagus nerve, effects of VNS on monoamines
      and mood improvement in patients with epilepsy who were treated with VNS,
      provided a rationale for further investigation in patients with primary mood
      disorders. VNS has been administered acutely for 10 weeks to 60 patients with
      treatment-resistant depression. Longer-term follow-up data has been analysed for
      the first 30 patients. Response rates have been at least 30% in the acute study.
      Similar to findings in epilepsy and in contrast to the usual results of long-term
      medication trials, longer term data regarding symptomatic and functional outcomes
      of depressed patients receiving VNS continue to look promising. As opposed to
      electroconvulsive therapy, VNS is not associated with cognitive impairment. These
      results have led to approval of VNS for the treatment of resistant depression
      (unipolar or bipolar) in both Europe and Canada. Currently, a pivotal double
      blind acute study is underway in the US.

PMID- 11583057
TI  - Current pharmacotherapy of allergic bronchopulmonary aspergillosis.
AB  - Although no well-designed studies have been carried out, the available data
      support the use of corticosteroids for acute exacerbations of allergic
      bronchopulmonary aspergillosis (ABPA). Neither the optimal steroid dose nor the
      duration of therapy has been standardised but limited data suggest the starting
      dose should be prednisone (approximately 0.5 mg/kg/day). The decision to taper
      steroids should be made on an individual basis, depending on clinical course. The
      available data suggest that clinical symptoms alone are inadequate to make such
      decisions, since significant lung damage may occur in asymptomatic patients.
      Increasing serum IgE levels, new or worsening infiltrate on chest radiograph and
      worsening spirometry suggest that steroids should be used. Multiple asthmatic
      exacerbations in a patient with ABPA suggest that chronic steroid therapy should
      be used. Itraconazole appears useful as a steroid sparing agent.

PMID- 11583058
TI  - C1-inhibitor: an anti-inflammatory reagent with therapeutic potential.
AB  - Excessive activation of the protein cascade systems often leads to severe
      inflammatory tissue destruction with potential life-threatening outcome. These
      include clinical disorders, such as capillary leak syndrome, septic shock,
      myocardial infarction and other ischaemia/reperfusion injuries, trauma, burns,
      multiple organ failure, as well as graft rejection. A therapeutic substitution of
      appropriate regulators appears to be a reasonable approach to reduce undesirable
      inflammatory reactions. C1-inhibitor, a multifunctional regulator of the various
      kinin-generating cascade systems, is frequently reduced in patients suffering
      from severe inflammation. C1-inhibitor concentrate has been used for decades as a
      substitution therapy to treat acute attacks in patients with hereditary
      angioedema. Studies including pathophysiologically relevant animal models now
      provide sufficient evidence that C1-inhibitor may also serve as an effective
      means to protect against inflammatory tissue injury. Promising clinical results
      are emerging which support C1-inhibitor as a candidate for therapy in severe
      inflammatory disorders. Although treatment with C1-inhibitor is regarded as safe,
      recent reports on possible side effects in certain clinical situations emphasise
      the importance of controlled clinical studies. The following review will focus on
      the impact of C1-inhibitor treatment on diseases, where complement contributes to
      the pathogenesis.

PMID- 11583060
TI  - The role of infectious agents in pulmonary and systemic vascular disease.
AB  - With emphasis on the pulmonary circulation, three general types of vascular
      disease are discussed: fibroproliferative (atherosclerosis), cellular
      proliferative (endothelial neoplasms) and inflammatory (granulomatous
      vasculitis). The causes of these phenotypic responses are invariably
      multifactorial, but infectious agents including viruses, Chlamydia, Helicobacter,
      Rickettsia, mycobacteria and other infectious agents have been increasingly
      implicated in the pathophysiology. The classifications of vascular diseases are
      complicated and confusing and many eponymous diseases are specific variations of
      more general disease processes. The pivotal role of the monocyte/macrophage and T
      cells is discussed, particularly with regard to intracellular infections. In
      addition to antimicrobial therapy, modifications of macrophage function by IFN
      gamma and blockade of TNF are attractive areas for therapeutic research. Diseases
      with many synergistic causes will probably also require multifaceted therapeutic
      interventions.

PMID- 11583059
TI  - The treatment of juvenile arthritis.
AB  - Until recently, two different classification systems for juvenile arthritis (JA)
      were utilised, each with its own terminology and subclassification. It has been
      recognised that particularly within the polyarticular and pauciarticular groups,
      many distinct subsets exist each with a different prognosis. As a result, a new
      classification system for JA has been developed. It is hoped that this will allow
      more accurate assessment of incidence and aetiology of the various subtypes in
      future generations and in time will allow therapy to be targeted at those most
      likely to achieve benefit. Since there is a new classification system for JA, the
      vast majority of published clinical studies were performed using the old
      classification system. For the purposes of this review, unless otherwise stated,
      the American College of Rheumatology classification will be used. This is
      outlined in Table 1 with clinical features of the major subtypes described in
      Table 3. This review will cover current best practice and discuss future
      directions for research using the recent advances in the treatment of rheumatoid
      arthritis (RA) as a model.

PMID- 11583061
TI  - Pharmacoeconomic issues of the treatment of gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in a
      gastroenterologist's practice. Gastroesophageal reflux (GER) describes the
      retrograde movement of gastric contents through the lower oesophageal sphincter
      (LES) to the oesophagus. GER can occur physiologically and may be accompanied by
      symptoms. The introduction of endoscopes and ambulatory devices for continuous
      monitoring of oesophageal pH (24 h pH monitoring) has led to great improvement in
      the ability to diagnose reflux disease and reflux-associated complications. The
      development of pathological reflux and GERD can be attributed to many factors.
      Pathophysiology of GERD includes transient lower oesophageal sphincter
      relaxations (TLESRs), incompetent LES because of a decreased lower oesophageal
      sphincter pressure (LESP) and deficient or delayed oesophageal acid clearance.
      Uncomplicated GERD may be treated by modification of lifestyle and eating habits
      in an early stage of GERD. The various agents currently used for treatment of
      GERD include mucoprotective substances, antacids, H2-blockers, prokinetics and
      proton pump inhibitors (PPIs). Although these drugs are effective, they do not
      necessarily influence the underlying causes of the disease by improving the
      oesophageal clearance, increasing the LESP or reducing the frequency of TLESRs.
      The following article gives an overview regarding current concepts of the
      pathophysiology and pharmacological treatment of GERD stressing on
      pharmacoeconomic issues of the treatment and discusses the advantages and
      disadvantages for step-up and step-down therapy.

PMID- 11583062
TI  - New developments in the prophylaxis and treatment of graft versus host disease.
AB  - Graft versus host disease (GVHD) remains the major obstacle to successful
      allogeneic bone marrow transplantation. Cyclosporin with methotrexate is the most
      common prophylactic regimen. Tacrolimus is associated with less GVHD and is
      gaining ground especially in unrelated donor transplants where current regimens
      are unsatisfactory. Mycophenolate mofetil (MMF) and rapamycin have not yet shown
      benefit in acute GVHD prophylaxis. In vivo T-cell depletion with Campath 1H or
      thymoglobulin used during transplant conditioning are increasingly used in place
      of ex vivo T-cell depletion, where results remain disappointing. Steroids remain
      first choice for therapy of GVHD but anti-CD25 antibodies, daclizumab or
      basiliximab are gaining popularity as second-line therapy ahead of ATG. Chronic
      GVHD is increasing with greater use of peripheral blood stem cell grafts and
      older patients. The combination of tacrolimus and MMF is promising for patients
      with extensive disease. Tolerance induction using CTLA-4-Ig, anti-CD40L,
      tresperimus and/or rapamycin may revolutionise GVHD therapy. However, due to the
      desirability of tumour intolerance, tolerance is likely to be developed in organ
      transplantation before bone marrow transplantation for traditional indications.
      Bone marrow transplants performed to induce organ tolerance may see increasing
      use of these agents. TNF blockade using infliximab or etanercept (Enbrel) is
      promising but the role of these agents is not yet defined.

PMID- 11583063
TI  - The role of cytochrome P450-mediated drug-drug interactions in determining the
      safety of statins.
AB  - The objectives of this review are to discuss the role of cytochrome P450 (CYP450)
      isoforms in drug metabolism, to explain differences in metabolism among the HMG
      CoA reductase inhibitors (HMGs, statins), to review drug-drug and drug-food
      interaction studies dealing with the HMGs, to present case reports dealing with
      HMG-related myopathy, to discuss major clinical implications of these case
      reports and to express an opinion of use of HMGs in clinical practice.

PMID- 11583064
TI  - AraC-based pharmacotherapy of chronic myeloid leukaemia.
AB  - In interferon-alpha (IFN) treated chronic phase chronic myeloid leukaemia (CML)
      patients, survival depends on individual risk profile and achievement of a
      complete haematological response (CHR) and a major cytogenetic response (MCR) (<
      35% Philadelphia-chromosome-positive metaphases). The highest cytogenetic
      response rates have been achieved with the combination of IFN and low-dose sc.
      AraC (10 mg daily to 10-20 mg/m2 for 10-14 days/month). Whether the higher
      cytogenetic response rates are also associated with a significant improvement of
      survival still remains controversial. The different results obtained from large
      randomised and observational trials may be due to the numbers of patients
      enrolled, distribution of risk profiles and the treatment schedule, which is
      influenced greatly by the haematological and gastrointestinal toxicity of AraC.
      An oral formulation (YNK01), which is lipophilic and resistant to deamination, is
      currently under investigation. Clinically, it has similar activity, but toxicity
      leads to discontinuation of treatment in a considerable proportion of patients.
      The clinical benefits may therefore be outweighed by the dose-limiting toxicity
      for both application forms. Combinations with other drugs, e.g., STI571 or
      homoharringtonine, have shown promising early results in vitro and in vivo.

PMID- 11583065
TI  - Etanercept in rheumatoid arthritis.
AB  - Etanercept (Enbrel, Immunex Corporation, Seattle, Washington, USA) is a new
      biological disease-modifying antirheumatic drug (DMARD) for the treatment of
      active rheumatoid arthritis (RA). It is one of two TNF-alpha blockers to be
      licensed for the treatment of active RA and is classified as a recombinant human
      soluble TNF receptor. The drug competitively inhibits the binding of TNF to cell
      surface receptors and thus renders TNF biologically inactive. In doing so,
      etanercept inhibits the pro-inflammatory effects of TNF and results in a
      reduction of joint inflammation in patients with RA. Etanercept has shown a
      statistically significant reduction in swollen and inflamed joint counts,
      biochemical markers such as erythrocyte sedimentation rate and C-reactive protein
      and shown significant improvements in quality of life measures (HAQ and global
      assessment scores) in all studies. In early disease, etanercept has shown a
      reduction in joint space narrowing equal to methotrexate (MTX) and a reduction in
      the appearance of new erosions significantly better than MTX after 1 year of
      treatment. Etanercept has a rapid onset of action which is significantly faster
      than standard DMARDs. Etanercept was well-tolerated in clinical trials. The
      commonest side effects were injection site reactions and upper respiratory tract
      infections. Etanercept therapy has resulted in serious infections in some
      patients and should be used with caution in any patient with a history of
      recurring infections or with disease states that may predispose to infections. In
      summary, etanercept is an effective and well-tolerated agent that is a
      significant breakthrough in the treatment of this disabling condition.

PMID- 11583066
TI  - Glatiramer acetate in the treatment of multiple sclerosis.
AB  - This review article summarises the initial preclinical studies as well as the
      different stages of clinical trials in multiple sclerosis (MS) with Copolymer 1
      (Cop 1), recently denoted glatiramer acetate. Experimental studies on autoimmune
      encephalomyelitis (EAE), the animal model of MS, as well as studies on the
      mechanism of action in both animals and humans are discussed. The review
      describes the early clinical trials which were followed by Phase II and III
      trials, culminating in FDA approval in 1996 for the treatment of relapsing
      remitting MS. The accumulated experience with glatiramer acetate indicates that
      its efficacy is apparently increased as a function of usage time while the
      favourable side effect profile is sustained. MRI studies revealed that treatment
      with glatiramer acetate resulted in a significant reduction of gadolinium (Gd)
      enhancing lesions. Ongoing clinical trials which might extend its usage or change
      its mode of delivery are also described. Glatiramer acetate appears to be a
      treatment of choice for the relapsing-remitting type of MS.

PMID- 11583067
TI  - Topical tacrolimus for the treatment of inflammatory skin diseases.
AB  - Chronic inflammatory skin disorders, such as atopic eczema, can cause
      considerable impairment of life quality. Their treatment is mainly driven by
      systemic or topical glucocorticosteroids which have the risk of many side
      effects. Recently, immunosuppressive macrolides which act via the inhibition of
      cytokine expression in T-lymphocytes have been shown to exert good therapeutic
      potency in inflammatory skin disorders. Cyclosporin, widely used in
      transplantation medicine, is also effective in psoriasis and atopic eczema but is
      not suitable for topical treatment. Tacrolimus (FK506) has been found to be 10
      100 times more potent than cyclosporin and to penetrate skin much better due to a
      lower molecular weight. Initial clinical investigations have shown efficacy of
      topical tacrolimus in patients with atopic eczema. Large multi-centre studies
      have proven that long-term therapy with 0.03% and 0.1% tacrolimus ointment
      reveals effectiveness and safety both in adults and in children with severe
      atopic eczema. A burning sensation at the site of application is the most
      frequently observed local side effect. Relevant systemic adverse events were not
      detected. In Japan and the US, the drug is already licensed for the treatment of
      atopic eczema. The European admission for the pharmaceutical market is expected
      in the year 2002. Tacrolimus represents a milestone in topical therapy of
      inflammatory skin disorders which has so far been dominated by corticosteroid
      formulations and gives hope for the development of further topical
      immunosuppressive agents of its class in the future.

PMID- 11583069
TI  - Gemfibrozil prevents major coronary events by increasing HDL-cholesterol and
      more.
AB  - A low concentration of plasma high-density lipoprotein (HDL)-cholesterol is a
      major risk factor for coronary heart disease (CHD). Gemfibrozil reduces the
      number of CHD events by 22% in 5 years. This marked beneficial effect can only
      partly be explained by the ability of gemfibrozil to increase HDL-cholesterol.
      Recently gemfibrozil has been shown to activate peroxisome proliferator-activated
      nuclear receptors. This activation leads to the increase in HDL-cholesterol and
      to a decrease in vascular wall inflammation and other changes in vascular
      function. These vascular effects of gemfibrozil may contribute to the beneficial
      effects in CHD.

PMID- 11583068
TI  - Triamcinolone: new and old indications.
AB  - Triamcinolone is a commonly used synthetic corticosteroid that has recently been
      tested in a large clinical trial for chronic obstructive pulmonary disease and
      shown to have some benefits. To our knowledge, there are no reviews of the
      pharmacotherapy of triamcinolone. This review has a brief overview of the
      pharmacology of triamcinolone, followed by a discussion of the clinical trials
      with triamcinolone. Triamcinolone is used in the treatment of respiratory
      inflammation, rheumatoid arthritis and a variety of other inflammatory
      conditions.

PMID- 11583070
TI  - Autism unravelled conference--'the biology of autism--unravelled'.
AB  - Autism is a heterogeneous condition, currently with no single explanation for all
      of these findings presented at this conference. What conferences like this offer
      us, however, are possible courses of new research and the subsequent development
      of intervention strategies, both orthodox (pharmacological) and perhaps slightly
      unorthodox. Aside from the social and emotional issues for both the person with
      autism and their family, it has been estimated that the cost to the UK for
      lifetime care of one person with autism is approximately pounds sterling 3
      million. With the possibility of an epidemic of autism, is it not time to begin
      looking at the biomedical factors behind autism spectrum disorders more closely?

PMID- 11583071
TI  - Anxiety sensitivity: relations to psychopathy, DSM-IV personality disorder
      features, and personality traits.
AB  - Relatively few data are available concerning the relations between anxiety
      sensitivity (AS) and both abnormal and normal personality traits. In particular,
      little is known about the associations between AS and personality disorders,
      although Shostak and Peterson [Behav. Res. Ther. 28 (1990) 513.] hypothesized
      that AS would be negatively correlated with antisocial personality disorder
      (ASPD) and perhaps related conditions (e.g., psychopathy). We examined the
      relations between AS, as assessed by the AS Index (ASI), and measures of
      psychopathy/ASPD, personality disorder features. and personality traits in a
      sample of 104 undergraduates. The ASI was not significantly associated with
      global measures of psychopathy or ASPD, although it was negatively correlated in
      some cases with the core affective deficits of psychopathy. In addition, the ASI
      was positively correlated with features of several Clusters B (e.g., borderline)
      and C (e.g., dependent) personality disorders and with features of passive
      aggressive personality disorder. In addition, the ASI was positively associated
      with measures of several normal-range personality traits, including trait
      anxiety, alienation, well being, Negative Emotionality, and Constraint. Some,
      although not all, of the abnormal and normal personality correlates of the ASI
      were attributable to the variance shared by the ASI with trait anxiety measures.
      Implications and limitations of the present findings for the correlates and
      etiology of AS are outlined.

PMID- 11583072
TI  - Home-based behavior therapy for obsessive-compulsive disorder: a case series with
      data.
AB  - The effectiveness of "home-based" exposure and response prevention was assessed
      in a series of 11 subjects with obsessive-compulsive disorder (OCD). Patients
      received 24 treatment sessions in a range of natural settings and situations.
      Sixty-four percent of the patients responded to behavior therapy in these
      settings, and 36% achieved lasting improvements in their OCD symptoms.
      Implications for the impact on consumers of this seldom-used application of
      behavior therapy are discussed and some recommendations for future research are
      made.

PMID- 11583073
TI  - A priori expectancy bias in patients with panic disorder.
AB  - BACKGROUND: Several studies have indicated that phobic participants tend to
      overassociate fear-relevant stimuli and aversive outcomes, i.e, they show a
      covariation bias. Such a bias seems to be a powerful way to confirm danger
      expectations and enhance fear. Therefore, a covariation bias might be an
      important factor in the maintenance of fear. METHODS: To investigate a
      covariation bias in patients with panic disorder, we had 29 patients and 29
      healthy control participants rate the a priori probabilities with which they
      would expect pictures of mushrooms, spiders, erotic scenes, and emergency
      situations to be paired with a tone, shock, or nothing. RESULTS: This is the
      first study to show that patients with panic disorder specifically overestimate
      the association between panic-relevant stimuli and a following negative
      consequence. This distorted contingency expectancy represents a panic-specific
      covariation bias, since it was not observable for other stimuli-consequence
      combinations and only to a significantly lesser degree in control participants.
      CONCLUSIONS: The underpinning hypothesis is that overestimation of threat plays a
      casual role in the origins and maintenance of anxiety. Thus anxiety may induce a
      covariation bias, which in turn may enhance the perceived threat, which in turn
      may intensify the anxiety etc. This reciprocal relationship between covariation
      bias and anxiety may have clinical implications for prediction and treatment in
      patients with panic disorder.

PMID- 11583075
TI  - Comparison of clinical characteristics in trichotillomania and obsessive
      compulsive disorder.
AB  - Fifteen patients with trichotillomania (TM) and 25 patients with obsessive
      compulsive disorder (OCD) were studied. All patients were evaluated using the
      structured clinical interview for DSM-III-R (SCID-P). TM and OCD patients were
      compared with respect to demographic variables and the scores obtained from the
      various scales. The TM group had a greater percentage of women and showed an
      earlier age at onset. There was no significant difference for depression and
      anxiety assessed with the STAI, HRSA, and HRSD between the groups. Compared to
      OCD patients, TM patients had significantly lower scores on the Y-BOCS. The two
      groups were similar on the measures of resistance to and control of the hair
      pulling/compulsive symptoms. We found significantly higher incidence of anxiety
      and depressive disorders, and Axis II personality disorders for OCD patients.
      These findings are discussed in the view of results from earlier reports.

PMID- 11583074
TI  - Fear of blushing: effects of task concentration training versus exposure in vivo
      on fear and physiology.
AB  - Patients with fear of blushing as the predominant complaint (N = 31) were
      randomly assigned to (1) exposure in vivo (EXP), or (2) task concentration
      training (TCT), in order to test the effect of redirecting attention above
      exposure only. In addition, it was investigated whether treatment reduced actual
      blush behavior; therefore, physiological parameters of blushing were measured
      during two behavioral tests. Half of the patients served as waiting-list controls
      first. Assessments were held before and after treatment, at 6-weeks, and at 1
      year follow-up. Both treatments appeared to be effective in reducing fear of
      blushing and realizing cognitive change. Yet, at posttest, TCT tended to produce
      better results with respect to fear of blushing. At 6-weeks follow-up, TCT
      produced significantly more cognitive change. At 1-year follow-up, patients
      further improved, while differential effects had disappeared. The reduction in
      fear of blushing was not paralleled by a reduction in actual blush behavior
      during the behavioral assessments. Thus, it seems that fear of blushing reflects
      a fearful preoccupation, irrespective of actual facial coloration.

PMID- 11583076
TI  - An analysis of the RCMAS Lie scale in a clinic sample of anxious children.
AB  - Examined Revised Children's Manifest Anxiety Scale (RCMAS) Lie scores in a sample
      of 284 anxious children. Lie scores were examined in relation to children's age,
      ethnicity/race, and gender, and in relation to Total Anxiety scores. The utility
      of Lie scores also was examined in terms of whether they were predictive of
      children's anxiety levels as rated by children themselves, parents, and
      clinicians. Between-group differences in children's Lie scores were examined as
      well. Results indicated that younger children had significantly higher Lie scores
      than older children, and Hispanic American children had significantly higher Lie
      scores than European American children. There were no significant gender
      differences in Lie scores, and no significant relation was found between RCMAS
      Lie scores and Total Anxiety scores for the total sample. Subgroup analyses
      indicated that Lie scores were predictive of children's anxiety levels. Results
      also indicated that Lie scores were significantly different between children who
      presented with anxiety disorders and children who presented with anxiety and
      externalizing disorders. Findings are discussed in terms of the usefulness of
      RCMAS Lie scores.

PMID- 11583077
TI  - Revictimization and information processing in women survivors of childhood sexual
      abuse.
AB  - This study examined the effect of sexual revictimization on information
      processing of trauma-related stimuli in a sample of child sexual abuse (CSA)
      survivors diagnosed with posttraumatic stress disorder (PTSD). Fifty-one
      treatment-seeking women participated in this study. Participants completed the
      Sexual Experiences Survey regarding sexual revictimization in the last 6 months
      and performed a modified emotional Stroop task in which they named the colors of
      neutral words (e.g., apple), general threat words (e.g., malignant and death),
      and sexual/victimization words (e.g., penis and abuser). As predicted, the
      revictimized participants (n = 16) took significantly longer to color-name
      sexual/victimization words than did the nonrevictimized participants. These
      results suggest that revictimization serves to prime preexisting "trauma" memory
      networks, thereby amplifying the impact of childhood sexual trauma on selective
      attention toward trauma-related stimuli.

PMID- 11583078
TI  - Identification of a new gene product of PKIbeta by HPLC-ESIMS.
AB  - An identification method using high-performance liquid chromatography combined
      with electrospray mass spectrometry (HPLC-ESIMS) has been developed to verify an
      expressed gene product of kinase inhibitor (PKIbeta). This protein was expressed
      in this university for the first time from a newly cloned gene in the cDNA
      library of human fetal brain. The measured MW (8468.9 Da) of PKIbeta-78 was
      consistent with expectations. The gene product of PKIbeta-78 was monitored by
      ESIMS to ensure there was no mis-expressed PKIbeta-70 in the process of gene
      engineering. The peptide mapping of PKIbeta-78 and its partial sequence were,
      furthermore, determined. By database searching based on the experimental MWs and
      partial sequences provided, it was verified that this gene product is a new
      protein. The pseudosubstrate site and leucine-rich site for the function region
      of PKIbeta-78 are also confirmed.

PMID- 11583079
TI  - Microdetermination of proteins with the arsenazo-DBN-Al(III) complex by Rayleigh
      light-scattering technique and application of the method.
AB  - The determination of proteins with arsenazo-DBN and Al3+ by Rayleigh light
      scattering (RLS) is described. The weak RLS of arsenazo-DBN and BSA can be
      enhanced greatly by addition of Al3+ in the pH range 5.3-7.0; this resulted in
      two enhanced RLS signals at 420-440 nm and 460-480 nm. The reaction between
      arsenazo-DBN, Al3+, and proteins was studied and a new method was developed for
      quantitative determination of proteins. This method is very sensitive (0.34-41.71
      microg mL(-1) for bovine serum albumin, BSA, and 0.29-53.41 microg mL(-1) for
      human serum albumin, HSA), rapid (< 2 min), simple (one step), and tolerant of
      most interfering substances. The effects of different surfactants were also
      examined. When these proteins were determined in four human serum samples the
      maximum relative error was not more than 2% and the recovery was between 97 and
      103%.

PMID- 11583080
TI  - A collision model for DNA separation by capillary electrophoresis in dilute
      polymer solution.
AB  - A theoretical description, based on chemical kinetics and electrochemistry, is
      given of DNA separation in dilute polymer solution by capillary electrophoresis.
      A self-consistent model was developed leading to predictions of the DNA
      electrophoretic velocity as a function of the experimental conditions--polymer
      concentration, temperature, and electric field strength. The effect of selected
      experimental variables is discussed. The phenomena discussed are illustrated for
      the example of 100 bp DNA ladder separation in dilute HPMC solution by capillary
      electrophoresis. This model is the first single model that can fully explain the
      dependence of DNA electrophoretic velocity on electrophoretic conditions.

PMID- 11583081
TI  - Solid-substrate room-temperature phosphorescence study on zinc(II) and tin(IV)
      protoporphyrins and their interaction with DNA.
AB  - The solid-substrate room-temperature phosphorescence (SS-RTP) of two commercially
      available metalloporphyrin compounds, zinc(II) protoporphyrin (ZnPP) and tin(IV)
      protoporphyrin (SnPP) has been studied. Strong and stable RTP signals of the two
      metalloporphyrins in neutral to weakly basic solutions can be simply induced on
      filter paper without addition of external heavy atom perturbers. Their emission
      bands appeared at 723 nm for ZnPP and 718 nm for SnPP at an excitation wavelength
      of 417 nm. Compared with SnPP, ZnPP is a better RTP probe for DNA because its RTP
      enhancement effect is much higher under the same experimental conditions. The
      interaction of ZnPP with DNA at pH 8.5 gives an apparent binding constant of 9.1
      x 10(3) which is similar to that of the cationic porphyrin absorption probe
      CuTMPyP (copper (II)- tetrakis(4-N-methylpyridyl)porphine complex). Hydrogen
      bonding between the monocarboxylic acid substituent of ZnPP and the base pairs of
      DNA plays a crucial role in the binding.

PMID- 11583082
TI  - Renewable amperometric immunosensor for complement 3 assay based on the sol-gel
      technique.
AB  - A renewable amperometric immunosensor based on the sol-gel technique has been
      constructed by dispersing graphite, complement 3 (C3) antiserum, and sol-gel at
      low temperature. The prepared immunosensor is rigid, porous, and has a renewable
      external surface. A competitive binding assay has been used to determine C3 in
      human serum with the aid of C3 labeled with horseradish peroxidase. The enzyme
      labeled antigen can readily diffuse toward the encapsulated antibody, which
      retains its binding properties. The experimental conditions for the assay with
      the biocomposite, including the loading of C3 antiserum in the biocomposite, the
      amount of labeled C3 in incubation solution, incubation time, and temperature,
      have been optimized. Using C3 labeled with horseradish peroxidase, and o-AP as
      the substrate, amperometric detection at -150 mV (relative to the SCE) results in
      a linear detection range of 1.17-35.1 microg mL(-1), with a detection limit of
      0.56 microg mL(-1). Serum samples have been assayed and the results demonstrate
      the feasibility of the proposed immunosensor for clinical analysis. The surface
      of the immunosensor can be renewed simply by polishing to obtain a fresh
      immunocomposite ready to use in a new competitive assay.

PMID- 11583083
TI  - Development and certification of a coal fly ash certified reference material for
      selected polycyclic aromatic hydrocarbons.
AB  - The development and certification of a coal fly ash certified reference material
      (CRM) for polycyclic aromatic hydrocarbons (PAH) is described; this is the first
      natural matrix CRM for organic environmental analysis in China. The homogeneity
      and stability of this material have been tested by HPLC. The concentrations of
      several PAH were determined by use of two independent, different methods--solvent
      extraction-HPLC analysis with UV detection coupled with fluorescence detection
      (FLD) and solvent extraction, isolation with a silica column, and GC analysis
      with flame ionization detection (FID). Five certified values were determined:
      phenanthrene 7.1 +/- 2.6 microg g(-1), anthracene 2.0 +/- 0.8 microg g(-1),
      fluoranthene 7.4 +/- 1.9 microg g(-1), pyrene 7 +/- 2 microg g(-1), and
      benzo[a]pyrene 1.3 +/- 0.3 microg g(-1). Reference values for several other PAH
      are also suggested.

PMID- 11583084
TI  - Speciation of rare earth elements in soil by sequential extraction then HPLC
      coupled with visible and ICP-MS detection.
AB  - The distribution of rare earth elements (REE) in a pooled soil sample collected
      from Zhangzhou, Fujian Province, China, was screened by a five-step sequential
      extraction procedure coupled with ICP-MS determination after preconcentration of
      REE and removal of the matrix by extraction with 1-phenyl-3-methyl-4-benzoyl-5
      pyrazolone (HPMBP). The results showed that the distribution of REE in the
      different fractions of the pooled soil sample studied followed the order soluble
      species (46.76%) > species bound to organic matter (22.08%) > species in the
      residue (16.77%) > species bound to Fe-Mn oxides (2.02%). An effective method for
      speciation of REE, which utilized weak cation-exchange HPLC separation hyphenated
      with post-column derivatization and visible or on line ICP-MS detection, was,
      moreover, developed and successfully applied to the speciation of REE in the
      soluble extract of the pooled soil sample. The stability of known complexes of
      lanthanum during the HPLC separation was investigated with fluoride, citrate, and
      ethylenediamine tetraacetic acid (EDTA) chosen as ligands modeling those in the
      soil. REE in the soluble extract of the pooled soil sample were subsequently
      classified into three types of species--< or = +1 charged complexes (negatively
      charged, neutral, and +1 charged), +2 charged complexes, and "free" REE species.
      This method is expected to be useful for identification of bioavailable (or
      toxic) species of REE in environmental samples.

PMID- 11583085
TI  - Optical rubbery ormosils sensor for the detection of ammonia.
AB  - Rubbery ormosil films with immobilized aminofluorescein (AF) were investigated to
      develop an optochemical sensor for the determination of ammonia in water. The gel
      precursors with tetramethoxysilane (TMOS) and dimethyldimethoxysilane (DiMeDMOS)
      were deposited on glass supports, and characterized in terms of response to pH,
      and to dissolved ammonia at constant pH. After preconditioning the sensing film
      was stable for 6 months. The detection limit for ammonia in water was 0.2 microg
      mL(-1) (S/N 2), the response being linearly dependent on concentration in the
      range of 0.5 to 80 microg mL(-1) ammonia. The response time was less than 5 min.
      The effects of sodium chloride concentration, temperature, and coexisting metal
      ions and compounds were investigated.

PMID- 11583086
TI  - Kinetic studies on the mechanism of atomization in electrothermal atomic
      absorption spectrometry with and without chemical modifiers.
AB  - Over the past decade a few methods for determining kinetic data for atom
      formation from the absorption signal in electrothermal atomic absorption
      spectrometry (ETAAS) have been developed in the author's laboratory. These
      approaches include improvement to the Smets method, and development of new
      methods for simultaneous determination of kinetic order and activation energy for
      atom formation at increasing or constant temperatures. The steady-state
      approximation and first-order kinetic assumption for atom formation have been
      avoided during their derivation. One of the most distinct features of these new
      methods is their suitability for quantitative determination of the kinetic order
      for atom formation from absorption signals under normal analytical conditions,
      even for atomization processes with fractional reaction orders and/or with
      multiple mechanisms. The application of the developed methods to the study of the
      mechanism of atomization in the graphite-furnace atomizer, with and without
      chemical modifiers, is reviewed with emphasis on research work in the authors'
      laboratory.

PMID- 11583087
TI  - A simple flow-injection on-line clean-up system for microwave plasma-torch atomic
      emission spectrometry.
AB  - A simple flow injection (FI) on-line clean-up system has been developed for
      microwave plasma-torch atomic emission spectrometry (MPT-AES). A non-selective
      strongly acidic cation-exchange resin was used to achieve the goal of "on-line
      clean-up". Ag and Zr, which form halogen-complex anions in halide acid media, and
      Cr, Mo, and P, which exist as acid group anions or acids (neutral) in acidic
      solution, were determined and the interfering matrix cations were removed on
      line. Satisfactory analytical results were obtained from some practical samples
      by use of this procedure.

PMID- 11583088
TI  - Flow-injection chemical vapor-generating procedure for the determination of Au by
      atomic absorption spectrometry.
AB  - Volatile Au species in an acidified medium were generated at room temperature by
      reduction with NaBH4 in acidified aqueous medium using a flow-injection chemical
      vapor-generation atomic absorption spectrometric (FI-CVG-AAS) system in the
      presence of micro amounts of sodium diethyldithiocarbamate (DDTC). Precision of
      2.0% RSD (n = 11, 2.0 mg L(-1) level) was obtained at a sample throughput of 180
      h(-1). A detection limit of 24 ng mL(-1) (3sigma) was obtained with 300 microL
      sample solution. The method was used for the determination of gold in ore sample
      digests, and the results obtained agreed well with those obtained by flame AAS.

PMID- 11583089
TI  - The kinetics and thermodynamics of surfactants in solvent sublation.
AB  - Solvent sublation has been performed on very dilute solutions of one cationic
      surfactant, hexadecylpyridinium chloride (HPC), and one anionic surfactant,
      dodecylbenzenesulfonic acid (LBS). Some thermodynamic values were obtained, e.g.
      molecular areas, A0, which are 50.0 and 47.7 A2/molecule, respectively, for HPC
      and LBS, and free adsorption energies, delta G(o)ads, which are -33.17 and -43.58
      kJ mol(-1), respectively, for HPC and LBS. The kinetics were determined for a
      range of temperatures and gas flow-rates. Although the processes of solvent
      sublation of the two surfactants obey first-order kinetics, the respective
      adsorption mechanisms of HPC and LBS in the solvent sublation process were
      different. The pH and the presence of KCl and ethanol had no effect on the
      solvent sublation of LBS. The apparent active energy was calculated as 8.11 kJ
      mol(-1).

PMID- 11583090
TI  - Nickel and strontium nitrates as modifiers for the determination of selenium in
      wine by Zeeman electrothermal atomic absorption spectrometry.
AB  - A mixed matrix modifier of nickel and strontium nitrates was used as a chemical
      modifier for the determination of selenium in wines by Zeeman electrothermal
      atomic absorption spectrometry. Wine samples were heated on a boiling water bath
      with small amounts of nitric acid and hydrogen peroxide. For complete elimination
      of interference, especially from sulfates and phosphates, selenium is complexed
      with ammonium pyrolidinedithiocarbamate (APDTC), extracted into methyl isobutyl
      ketone (MIBK), and measured by ETAAS. The graphite furnace temperature program
      was optimized for both aqueous and organic solutions. Pyrolysis temperatures of
      1300 degrees C and 800 degrees C were chosen for aqueous and organic solutions,
      respectively; 2700 degrees C and 2100 degrees C were used as optimum atomization
      temperatures for aqueous and organic solutions, respectively. The optimum
      modifier mass established is markedly lower than those presented in the
      literature. The platform atomization ensures pretreatment stabilization up to
      1100 degrees C and 1600 degrees C, respectively, for organic and aqueous selenium
      solutions. The procedure was verified by the method of standard addition. The
      investigated wine samples originated from the different regions of the Republic
      of Macedonia. The selenium concentration varied from not detectable to 0.93
      microg L(-1).

PMID- 11583092
TI  - A study on the detection of weak photoacoustic signals by stochastic resonance.
AB  - On the basis of stochastic resonance (SR) theory a study of the detection of
      photoacoustic (PA) signals without a lock-in amplifier is presented. The
      applicability of the SR method is investigated both with simulated signals
      calculated by use of a Gaussian model and with experimental PA signals. Signal-to
      noise ratio (SNR) is improved substantially by adjusting the properties of a non
      linear system to realize SR. By use of this method the lock-in amplifier can be
      removed from a PA spectrometer.

PMID- 11583091
TI  - Adsorptive behavior and electrochemical determination of the anti-fungal agent
      ketoconazole.
AB  - The adsorptive properties and electrochemical behavior of ketoconazole, an oral
      anti-fungal agent, are demonstrated at a glassy carbon electrode. The adsorption
      of the compound obeys the Frumkin isotherm with an interaction factor (alpha) of
      0.985 and adsorptive coefficient (beta) of 1.98 x 10(6) L mol(-1). The Gibbs
      energy of adsorption (deltaG) is -3.59 x 10(4) J mol(-1) at 25 degrees C. A very
      sensitive electroanalytical method has been developed for determination of the
      drug with a detection limit of 4.0 x 10(-11) mol L(-1). Relationships between
      stripping current and concentration of ketoconazole were linear in the range 10(
      6)-10(-10) mol L(-1) with different preconcentration periods. The method has been
      used to measure the ketoconazole content of tablets.

PMID- 11583093
TI  - Highly selective thiocyanate poly(vinyl chloride) membrane electrode based on a
      cadmium-Schiff's base complex.
AB  - A PVC membrane electrode based on a cadmium-salen (N,N'-bis-salicylidene-1,2
      ethylenediamine) complex as an anion carrier is described. The electrode has an
      anti-Hofmeister selectivity sequence with a preference for thiocyanate at pH 1.5
      11.0. It has a linear response to thiocyanate from 1.0 x 10(-6) to 1.0 x 10(-1)
      mol L(-1) with a slope of 59.1 +/- 0.2 mV per decade, and a detection limit of 7
      x 10(-7) mol L(-1). This electrode has high selectivity for thiocyanate relative
      to many common organic and inorganic anions. The proposed sensor has a fast
      response time of approximately 15 s. It was applied to the determination of
      thiocyanate in a milk sample.

PMID- 11583094
TI  - Solid-phase microextraction-gas chromatographic determination of volatile
      monoaromatic hydrocarbons in soil.
AB  - Benzene, toluene, ethylbenzene, three isomers of xylene, and cumene have been
      isolated and enriched from soil samples by a combination of water extraction at
      room and elevated temperature and headspace-solid-phase microextraction before
      their gas chromatographic-mass spectrometric (GC-MS) determination. The
      conditions used for all stages of sample preparation and chromatographic analysis
      were optimized. Analytes sampled on a polydimethylsiloxane-coated solid-phase
      microextraction fiber were thermally desorbed in the split/splitless injector of
      a gas chromatograph (GC) coupled with a mass spectrometer (MS). The desorption
      temperature was optimized. The GC separation was performed in a capillary column.
      Detection limits were found to be of the order of ca. 1 ng g(-1). Relative
      recoveries of the analytes from soils were found to be highly dependent on soil
      organic-matter content and on compound identity; they ranged from ca 92 to 96%
      for sandy soil (extraction at room temperature) and from ca 27 to 55% for peaty
      soil (extraction at elevated temperature). A few real-world soil samples were
      analyzed; the individual monoaromatic hydrocarbon content ranged from below
      detection limits to 6.4 ng g(-1) for benzene and 8.1 for the total of p- + m
      xylene.

PMID- 11583095
TI  - The determination of low lead levels in the bone of lead-depleted mice by
      graphite furnace atomic absorption spectrometry.
AB  - Low lead levels in the femurs of mice fed with a lead-depleted diet have been
      determined by use of electrothermal atomic absorption spectrometry with Zeeman
      effect background correction. The method is based on the use of Mg(NO3)2/Pd as
      matrix modifier which enables significant reduction of the spectral interferences
      prevalent if chemical modifiers based on NH4H2PO4 with either Ca or Mg are used
      for samples rich in Ca3(PO4)2 matrix. The method was developed and validated by
      use of the NIST standard reference material 1486 bone. Bones were decomposed in a
      pressurized microwave-heated system using 70% nitric acid. Forty-three mice
      femurs, with a mass of 74.62 +/- 12.54 mg, were dissolved in concentrated nitric
      acid. The lead results found in SRM 1486 (1.25 +/- 0.15 microg g(-1), n = 9) were
      in good agreement with the certificate (1.335 +/- 0.014 microg g(-1)). Recoveries
      of 200 ng lead added to the SRM before or after digestion were 99.0 +/- 1.4% and
      98.5 +/- 1.6%, respectively. The lead detection limit in bone samples is 0.06
      microg g(-1) dry mass. This method is, therefore, suitable for the determination
      of very low lead levels (0.06-0.20 microg Pb kg(-1) bone) in the femurs of mice
      fed a diet with lead level of < 20 microg kg(-1).

PMID- 11583096
TI  - Determination of Mn, Fe, and Cu in chemically-treated wood pulps by the XRF
      addition method.
AB  - A rapid X-ray fluorescence addition method has been developed for quantification
      of the technically most important metals in wood pulp matrix (Mn, Fe, and Cu).
      Pretreatment consisted of just two steps: first, acid was added to the sample to
      achieve homogeneous distribution of the metals; the pulp was then pressed lightly
      on to Mylar film. Total analysis time was less than 10 min. The concentration
      range investigated was up to 15 mg kg(-1) for Mn and up to 5 mg kg(-1) for Fe and
      Cu. Metal concentrations in Scandinavian pulps are not expected to exceed these
      amounts. The quantification limit was 2 mg kg(-1) for all three metals. The
      reproducibilities and repeatabilities were concentration-dependent and varied
      between 3 and 19% and between 1 and 17%, respectively. The squares of the linear
      correlation coefficients between measured intensity and added metal concentration
      were 0.994, 0.950, and 0.932 for Mn, Fe, and Cu, respectively.

PMID- 11583097
TI  - Group separation of trace rare-earth elements by countercurrent chromatography
      for their determination in high-purity calcium chloride.
AB  - A method has been developed for the separation of the entire group of rare-earth
      elements from high-purity calcium chloride by countercurrent chromatography, and
      subsequent determination of the elements by ICP-MS. A solution of
      diphenyl[dibutylcarbamoylmethyl]phosphine oxide in chloroform (0.5 mol L(-1)) has
      been chosen as reagent for the extraction and preconcentration of trace rare
      earth elements from aqueous 5% CaCl2 solution, 3 mol L(-1) in HNO3 and 0.1 mol L(
      1) in HClO4. The analytes are back-extracted into a small volume of water and the
      aqueous eluate is subjected to ICP-MS measurements. The performance
      characteristics of the procedure developed have been checked by use of the
      standard addition technique and a real CaCl2 sample (Merck product) has been
      analyzed. The results obtained demonstrate the applicability of countercurrent
      chromatography to the determination of ultratrace elements.

PMID- 11583098
TI  - Direct determination of ultra-trace amounts of acetone by corona-discharge ion
      mobility spectrometry.
AB  - The capability of corona-discharge ion mobility spectrometry (CD-IMS) in the
      quantitative determination of acetone has been evaluated. Generally, in IMS the
      signal intensity of a product ion is not a linear function of the sample
      concentration. A linear calibration curve was, however, obtained by plotting
      ln(R0+/R0+-P+) against acetone concentration, where, R0+ is the original reactant
      ion density and P+ is the sum of all the product ion densities. The acetone
      detection limit was 60 ng m(-3) and its dynamic range was three orders of
      magnitude.

PMID- 11583099
TI  - Spectrofluorimetric determination of thiols by use of N[P-(2
      benzoxazolyl)phenyl]maleimide.
AB  - The weak fluorescence of N-[P-(2-benzoxazolyl)phenyl]maleimide (BOPM) can be
      greatly enhanced by thiol-containing compounds. A sensitive and simple
      spectrofluorimetric method based on the use of BOPM has been developed for the
      determination of thiols such as cysteine (Cys) and reduced glutathione (GSH).
      Calibration plots were linear in the concentration range from 0 to 1.6 x 10(-7)
      mol L(-1) for Cys and 0 to 1.7 x 10(-7) mol L(-1) for GSH. The detection limits
      (3a) were 2.36 x 10(-10) mol L(-1) for Cys and 1.49 x 10(-10) mol L(-1) for GSH.
      Many other amino acids (present at 100-fold greater concentrations) did not
      interfere with the determination. The proposed method has been used for the
      determination of Cys in protein hydrolysate and cystine electrolyte or GSH in
      serum, with recoveries of 95.4-103.7%.

PMID- 11583100
TI  - Development of a low-cost microfluidic capillary-electrophoresis system coupled
      with flow-injection and sequential-injection sample introduction (review).
AB  - Microfabrication techniques used for the production of MEMS (micro electro
      mechanical systems) have been successfully used to produce highly efficient
      microfluidic capillary electrophoresis chip systems. A limitation of this
      approach are the difficulties associated with the creation of the micrometer
      sized structures in glass or other substrates, which currently involve
      specialized and expensive lithographic and etching processes. A further
      limitation is that hitherto most microfluidic chips are not designed for
      continuous introduction of a series of different samples, which limits the
      overall throughput of such systems. This article reviews the development of a
      microfluidic system for rapid CE separations, produced at a low cost of less than
      a dollar each, using equipment and materials readily available in the ordinary
      laboratory. Applications of the system, after coupling to flow-injection and/or
      sequential-injection sample introduction, for the determination of FITC-labeled
      amino acids by laser-induced fluorescence, trace metals by chemiluminescence,
      carbohydrates by amperometry, and inorganic and organic anions by indirect UV
      absorbance are exemplified to illustrate the performance and versatility of the
      microfluidic system.

PMID- 11583101
TI  - Analytical methodologies for aluminium speciation in environmental and biological
      samples--a review.
AB  - It is recognized that aluminium (Al) is a potential environmental hazard. Acidic
      deposition has been linked to increased Al concentrations in natural waters.
      Elevated levels of Al might have serious consequences for biological communities.
      Of particular interest is the speciation of Al in aquatic environments, because
      Al toxicity depends on its forms and concentrations. In this paper, advances in
      analytical methodologies for Al speciation in environmental and biological
      samples during the past five years are reviewed. Concerns about the specific
      problems of Al speciation and highlights of some important methods are elucidated
      in sections devoted to hybrid techniques (HPLC or FPLC coupled with ET-AAS, ICP
      AES, or ICP-MS), flow-injection analysis (FIA), nuclear magnetic resonance (27Al
      NMR), electrochemical analysis, and computer simulation. More than 130 references
      are cited.

PMID- 11583102
TI  - A new method of Fourier-transform smoothing with ratio spectra derivative
      spectrophotometry.
AB  - A new method which combines Fourier-transform smoothing with ratio spectra
      derivative spectrophotometry has been developed for analysis of binary and
      ternary mixtures. The method proposed has been applied to the simultaneous
      determination of a binary mixture of 0.974-2.026 x 10(-2) g L(-1) nitrate and
      nitrite and to a ternary mixture of 1.840-3.888 x 10(-3) g L(-1) histidine,
      phenylalanine, and tryptophan. The relative standard derivations are between 0.07
      and 5.3% for the former system, and between 0.5 and 7.3% for the latter. The
      results show that the method proposed is more accurate than multiple linear
      regression.

PMID- 11583103
TI  - Morphological evolution of athletes over the 20th century: causes and
      consequences.
AB  - Over the course of the past century it has become increasingly difficult to find
      athletes of the size and shape required to compete successfully at the highest
      level. Sport is Darwinian in that only the 'fittest' reach the highest level of
      participation. Not every physical characteristic could be expected to play a role
      in this selection process, but two that are important and for which substantial
      data assemblies exist, are height and mass. Measurements of elite athlete sizes
      were obtained from a variety of sources as far back as records allowed. We
      charted the shift in these anthropometric characteristics of elite sportspeople
      over time, against a backdrop of secular changes in the general population.
      Athletes in many sports have been getting taller and more massive over time; the
      rates of rise outstripping those of the secular trend. In open-ended sports, more
      massive players have an advantage. Larger players average longer careers and
      obtain greater financial rewards. In some sports it is equally difficult to find
      athletes small enough to compete. In contrast, there are sports that demand a
      narrow range of morphological characteristics. In these sports the size of the
      most successful athletes over the century has remained constant, despite the
      drift in the population characteristics from which they are drawn. A number of
      social factors both drive and are driven by the search for athletes of
      increasingly rare morphology. These include globalisation and international
      recruitment, greater financial and social incentives, and the use of special
      training methods and artificial growth stimuli. In many sports the demand for a
      specific range in body size reinforces the need to adopt questionable and illegal
      behaviours to reach the required size and shape to compete at the top level.
      Future scenarios also include 'gene-farming' through assortative mating and
      athlete gamete banks.

PMID- 11583104
TI  - Caffeine and exercise: metabolism, endurance and performance.
AB  - Caffeine is a common substance in the diets of most athletes and it is now
      appearing in many new products, including energy drinks, sport gels, alcoholic
      beverages and diet aids. It can be a powerful ergogenic aid at levels that are
      considerably lower than the acceptable limit of the International Olympic
      Committee and could be beneficial in training and in competition. Caffeine does
      not improve maximal oxygen capacity directly, but could permit the athlete to
      train at a greater power output and/or to train longer. It has also been shown to
      increase speed and/or power output in simulated race conditions. These effects
      have been found in activities that last as little as 60 seconds or as long as 2
      hours. There is less information about the effects of caffeine on strength;
      however, recent work suggests no effect on maximal ability, but enhanced
      endurance or resistance to fatigue. There is no evidence that caffeine ingestion
      before exercise leads to dehydration, ion imbalance, or any other adverse
      effects. The ingestion of caffeine as coffee appears to be ineffective compared
      to doping with pure caffeine. Related compounds such as theophylline are also
      potent ergogenic aids. Caffeine may act synergistically with other drugs
      including ephedrine and anti-inflammatory agents. It appears that male and female
      athletes have similar caffeine pharmacokinetics, i.e., for a given dose of
      caffeine, the time course and absolute plasma concentrations of caffeine and its
      metabolites are the same. In addition, exercise or dehydration does not affect
      caffeine pharmacokinetics. The limited information available suggests that
      caffeine non-users and users respond similarly and that withdrawal from caffeine
      may not be important. The mechanism(s) by which caffeine elicits its ergogenic
      effects are unknown, but the popular theory that it enhances fat oxidation and
      spares muscle glycogen has very little support and is an incomplete explanation
      at best. Caffeine may work, in part, by creating a more favourable intracellular
      ionic environment in active muscle. This could facilitate force production by
      each motor unit.

PMID- 11583105
TI  - Exercise prescription for the elderly: current recommendations.
AB  - The benefits for elderly individuals of regular participation in both
      cardiovascular and resistance-training programmes are great. Health benefits
      include a significant reduction in risk of coronary heart disease, diabetes
      mellitus and insulin resistance, hypertension and obesity as well as improvements
      in bone density, muscle mass, arterial compliance and energy metabolism.
      Additionally, increases in cardiovascular fitness (maximal oxygen consumption and
      endurance), muscle strength and overall functional capacity are forthcoming
      allowing elderly individuals to maintain their independence, increase levels of
      spontaneous physical activity and freely participate in activities associated
      with daily living. Taken together, these benefits associated with involvement in
      regular exercise can significantly improve the quality of life in elderly
      populations. It is noteworthy that the quality and quantity of exercise necessary
      to elicit important health benefits will differ from that needed to produce
      significant gains in fitness. This review describes the current recommendations
      for exercise prescriptions for the elderly for both cardiovascular and
      strength/resistance-training programmes. However, it must be noted that the
      benefits described are of little value if elderly individuals do not become
      involved in regular exercise regimens. Consequently, the major challenges facing
      healthcare professionals today concern: (i) the implementation of educational
      programmes designed to inform elderly individuals of the health and functional
      benefits associated with regular physical activity as well as how safe and
      effective such programmes can be; and (ii) design interventions that will both
      increase involvement in regular exercise as well as improve adherence and
      compliance to such programmes.

PMID- 11583106
TI  - Advances in the management of traumatic anterior and atraumatic multidirectional
      shoulder instability.
AB  - Dislocation of the shoulder is a common and often disabling injury to an athlete.
      Most shoulder dislocations are traumatic in origin, occur in the anterior
      direction and result in stretching and detachment of the anterior capsule and
      labrum. The most frequent adverse sequel of shoulder dislocation is recurrence-
      an event that occurs most commonly in active individuals and less frequently with
      age. In the past, many operative procedures failed to address the anatomical
      disruptions of shoulder instability. Recently, an enhanced understanding of
      shoulder instability pathoanatomy and significant technological advances have
      resulted in surgical procedures for shoulder instability that are less
      interventional and have focused on restoring disrupted static constraints.

PMID- 11583107
TI  - Practice care guidance for clinicians participating in the management of head and
      neck cancer patients in the UK. Drawn up by a Consensus Group of Practising
      Clinicians.
AB  - This paper outlines the minimum standards to be achieved by a head and neck
      cancer unit. It proposes a functional centre comprising associated units all of
      which will adopt the same standards and commitment to quality. The paper also
      proposes a suggested pathway for patients, describing various levels of care
      through which patients may pass as appropriate together with minimum standards
      relating to those levels. The skills and training required by various clinicians
      at different levels are outlined. The paper also describes a multidisciplinary
      clinic seen as the core service to patients and describes appropriate standards
      relevant to the clinic. The way forward now is to discuss and refine these
      standards as representative of appropriate high quality care to be offered to
      patients, and if these standards are agreed, to ensure that development proposals
      are established to set up the relevant services.

PMID- 11583108
TI  - Activation of estrogen receptor beta is a prerequisite for estrogen-dependent
      upregulation of nitric oxide synthases in neonatal rat cardiac myocytes.
AB  - Physiological effects of estrogen on myocardium are mediated by two intracellular
      estrogen receptors, ERalpha and ERbeta, that regulate transcription of target
      genes through binding to specific DNA target sequences. To define the role of
      ERbeta in the transcriptional activation of both endothelial (eNOS) and inducible
      nitric oxide synthase (iNOS) in cardiac myocytes, we used the complete ER
      specific antagonist R,R-tetrahydrochrysene (R,R-THC). R,R-THC inhibited
      activation of iNOS/eNOS promoter-luciferase reporter constructs (iNOS/eNOS-Luc)
      in a dose-dependent fashion in COS7 cells selectively transfected with ERbeta,
      but failed to influence ERalpha-mediated increase of iNOS/ eNOS-Luc. In neonatal
      rat cardiomyocytes transfected with eNOS-Luc or iNOS-Luc, incubation with
      17betaestradiol (E2, 10(-8) M) for 24 h stimulated expression of eNOS and iNOS.
      R,R-THC (10(-5) M) completely inhibited this effect. Furthermore, eNOS and iNOS
      protein expression in cardiac myocytes induced by E2 was completely blocked by
      R,R-THC as shown by immunoblot analysis. Taken together, these results show that
      ERbeta mediates transcriptional activation of eNOS and iNOS by E2.

PMID- 11583109
TI  - Growth kinetics rather than stress accelerate telomere shortening in cultures of
      human diploid fibroblasts in oxidative stress-induced premature senescence.
AB  - WI-38 human diploid fibroblasts underwent accelerated telomere shortening (490
      bp/stress) and growth arrest after exposure to four subcytotoxic 100 microM tert
      butylhydroperoxide (t-BHP) stresses, with a stress at every two population
      doublings (PD). After subcytotoxic 160 microM H2O2 stress or five repeated 30
      microM t-BHP stresses along the same PD, respectively a 322 +/- 55 and 380 +/-
      129 bp telomere shortening was observed only during the first PD after stress.
      The percentage of cells resuming proliferation after stress suggests this
      telomere shortening is due to the number of cell divisions accomplished to reach
      confluence during the first PD after stress.

PMID- 11583110
TI  - Evolution of tuf genes: ancient duplication, differential loss and gene
      conversion.
AB  - The tuf gene of eubacteria, encoding the EF-tu elongation factor, was duplicated
      early in the evolution of the taxon. Phylogenetic and genomic location analysis
      of 20 complete eubacterial genomes suggests that this ancient duplication has
      been differentially lost and maintained in eubacteria.

PMID- 11583111
TI  - Identification of rod- and cone-specific phosducins in teleost retinas.
AB  - Phosducin (PD) is a regulatory protein of vertebrate phototransduction cascades.
      In mammalian retina, it has been thought that only one kind of PD commonly exists
      in both rods and cones. However, we have found two kinds of PD (OIPD-R and OIPD
      C) in the retina of a teleost, medaka (Oryzias latipes). In situ hybridization
      and immunohistochemical analysis demonstrated that OIPD-R and -C are selectively
      expressed in rods and cones, respectively. The antiserum against medaka PDs
      recognized two kinds of proteins in bluegill (Lepomis macrochirus) retina. These
      results suggest that rod- and cone-specific PDs exist in teleost retinas,
      probably creating differences in light adaptation between rods and cones.

PMID- 11583112
TI  - Transcriptional effect of hypoxia on placental leptin.
AB  - We observed recentlyl that placental leptin is markedly increased in
      preeclampsia. Since this disorder is associated with vascular disorders, we have
      tested the hypothesis that hypoxia regulates leptin expression. We show that
      hypoxia increased leptin mRNA and secretion in trophoblast-derived BeWo cells.
      This effect was mediated through leptin promoter activation. 5' deletion analysis
      allowed us to delineate two regions containing 1.87 kb and 1.20 kb of the
      promoter which conferred respectively high and low responsiveness to hypoxia.
      These data indicate that leptin is up-regulated by hypoxia through a
      transcriptional mechanism likely to involve distinct hypoxia-responsive cis
      acting sequences on the promoter.

PMID- 11583113
TI  - Prooxidant activity of melatonin promotes fas-induced cell death in human
      leukemic Jurkat cells.
AB  - The antioxidant activity of melatonin (MEL) has been considered to constitute
      part of its physiological as well as pharmacological effects. However, as
      described herein we found a profound prooxidant activity of micro- to millimolar
      concentrations of MEL in the human leukemic Jurkat cell line. This prooxidant
      effect was increased in glutathione-depleted cells and counteracted by
      antioxidants. As a consequence MEL promoted fas-induced cell death. These data
      therefore indicate that MEL may be a modulator of the cellular redox status, but
      does not necessarily act as an intracellular antioxidant.

PMID- 11583114
TI  - Molecular cloning and disruption of a novel gene encoding UDP-glucose:
      tetrahydrobiopterin alpha-glucosyltransferase in the cyanobacterium Synechococcus
      sp. PCC 7942.
AB  - The gene encoding UDP-glucose:tetrahydrobiopterin alpha-glucosyltransferase
      (BGluT) was cloned from the genomic DNA of Synechococcus sp. PCC 7942. The
      encoded protein consisting of 359 amino acid residues was verified in vitro and
      in vivo to be responsible for the synthesis of tetrahydrobiopterin (BH4)
      glucoside produced in the organism. The BGluT gene is the first cloned in
      pteridine glycosyltransferases and also a novel one cloned so far in UDP
      glycosyltransferases. The mutant cells disrupted in the BGluT gene produced only
      aglycosidic BH4 at a level of 8.3% of the BH4-glucoside in wild type cells and
      exhibited half of the wild type growth in normal photoautotrophic conditions.
      These results suggest that the glucosylation of BH4 is required for the
      maintenance of the high cellular concentration of the compound, thereby
      supporting the normal growth of Synechococcus sp. PCC 7942.

PMID- 11583115
TI  - Rapid functional analysis of protein-protein interactions by fluorescent C
      terminal labeling and single-molecule imaging.
AB  - Detection of protein-protein interactions is a fundamental step to understanding
      gene function. Here we report a sensitive and rapid method for assaying protein
      protein interactions at the single-molecule level. Protein molecules were
      synthesized in a cell-free translation system in the presence of Cy5-puro, a
      fluorescent puromycin, using mRNA without a stop codon. The interaction of
      proteins thus prepared was visualized using a single-molecule imaging technique.
      As a demonstration of this method, a motor protein, kinesin, was labeled with Cy5
      puro at an efficiency of about 90%, and the processive movement of kinesin along
      microtubules was observed by using total internal reflection microscopy. It took
      only 2 h from the synthesis of proteins to the functional analysis. This method
      is applicable to the functional analysis of various kinds of proteins.

PMID- 11583117
TI  - Lipolytic enzymes LipA and LipB from Bacillus subtilis differ in regulation of
      gene expression, biochemical properties, and three-dimensional structure.
AB  - Bacillus subtilis secretes the lipolytic enzymes LipA and LipB. We show here that
      they are differentially expressed depending on the composition of the growth
      medium: LipA is produced in rich and in minimal medium, whereas LipB is present
      only in rich medium. A comparison of biochemical characteristics revealed that
      LipB is thermostable at pH 11 but becomes thermolabile at pH 5. However,
      construction of a variant carrying the substitution A76G in the conserved lipase
      pentapeptide reversed these effects. The atomic coordinates from the LipA crystal
      structure were used to build a three-dimensional structural model of LipB, which
      revealed that 43 out of 45 residues different from LipA are surface-located
      allowing to rationalize the differences observed in the substrate preferences of
      the two enzymes.

PMID- 11583116
TI  - p90-RSK and Akt may promote rapid phosphorylation/inactivation of glycogen
      synthase kinase 3 in chemoattractant-stimulated neutrophils.
AB  - Stimulation of neutrophils with the chemoattractant fMet-Leu-Phe (fMLP) triggers
      phosphorylation/inactivation of the a- and beta-isoforms of glycogen synthase
      kinase 3 (GSK-3) with phosphorylation of the alpha-isoform predominating. These
      reactions were monitored with a phosphospecific antibody that only recognized the
      alpha- or beta-isoforms of GSK-3 when these proteins were phosphorylated on
      serine residues 21 and 9, respectively. Inhibitor studies indicated that
      phosphorylation of GSK-3alpha may be catalyzed by the combined action of p90-RSK
      and Akt and may represent a new strategy by which G protein-coupled receptors
      inactivate GSK-3. Inactivation of GSK-3 may be one of the mechanisms that delay
      apoptosis in fMLP-stimulated neutrophils.

PMID- 11583118
TI  - Discovery of a new inhibitor lead of adenovirus proteinase: steps toward
      selective, irreversible inhibitors of cysteine proteinases.
AB  - Using the computer docking program EUDOC, in silico screening of a chemical
      database for inhibitors of human adenovirus cysteine proteinase (hAVCP)
      identified 2,4,5,7-tetranitro-9-fluorenone that selectively and irreversibly
      inhibits hAVCP in a two-step reaction: reversible binding (Ki = 3.09 microM)
      followed by irreversible inhibition (ki = 0.006 s(-1)). The reversible binding is
      due to molecular complementarity between the inhibitor and the active site of
      hAVCP, which confers the selectivity of the inhibitor. The irreversible
      inhibition is due to substitution of a nitro group of the inhibitor by the nearby
      Cys122 in the active site of hAVCP. These findings suggest a new approach to
      selective, irreversible inhibitors of cysteine proteinases involved in normal and
      abnormal physiological processes ranging from embryogenesis to apoptosis and
      pathogen invasions.

PMID- 11583119
TI  - Regulation of p85alpha phosphatidylinositol-3-kinase expression by peroxisome
      proliferator-activated receptors (PPARs) in human muscle cells.
AB  - Regulation of p85a phosphatidylinositol-3-kinase (p85alphaPI-3K) expression by
      peroxisome proliferator-activated receptor (PPAR) activators was studied in human
      skeletal muscle cells. Activation of PPARgamma or PPARbeta did not modify the
      expression of p85alphaPI-3K. In contrast, activation of PPARalpha increased
      p85alphaPI-3K mRNA. This effect was potentiated by 9-cis-retinoic acid, an
      activator of RXR. Up-regulation of p85alphaPI-3K gene expression resulted in a
      rise in p85alphaPI-3K protein level and in an increase in insulin-induced PI3
      kinase activity. According to the role of p85alphaPI-3K in insulin action, these
      results suggest that drugs with dual action on both PPARgamma and PPARalpha can
      be of interest for the treatment of insulin resistance.

PMID- 11583120
TI  - Changing provider behavior: an overview of systematic reviews of interventions.
AB  - BACKGROUND: Increasing recognition of the failure to translate research findings
      into practice has led to greater awareness of the importance of using active
      dissemination and implementation strategies. Although there is a growing body of
      research evidence about the effectiveness of different strategies, this is not
      easily accessible to policy makers and professionals. OBJECTIVES: To identify,
      appraise, and synthesize systematic reviews of professional educational or
      quality assurance interventions to improve quality of care. RESEARCH DESIGN: An
      overview was made of systematic reviews of professional behavior change
      interventions published between 1966 and 1998. RESULTS: Forty-one reviews were
      identified covering a wide range of interventions and behaviors. In general,
      passive approaches are generally ineffective and unlikely to result in behavior
      change. Most other interventions are effective under some circumstances; none are
      effective under all circumstances. Promising approaches include educational
      outreach (for prescribing) and reminders. Multifaceted interventions targeting
      different barriers to change are more likely to be effective than single
      interventions. CONCLUSIONS: Although the current evidence base is incomplete, it
      provides valuable insights into the likely effectiveness of different
      interventions. Future quality improvement or educational activities should be
      informed by the findings of systematic reviews of professional behavior change
      interventions.

PMID- 11583121
TI  - Successes and failures in the implementation of evidence-based guidelines for
      clinical practice.
AB  - BACKGROUND: The development and implementation of (evidence-based) clinical
      practice guidelines is one of the promising and effective tools for improving the
      quality of care. However, many guidelines are not used after dissemination.
      Implementation activities frequently produce only moderate improvement. It is
      important to study specific guideline programs in detail to learn from their
      successes and failures. OBJECTIVES: Experiences with more than 10 years of
      development and dissemination of clinical guidelines for family medicine in the
      Netherlands are presented in this paper. RESULTS: More than 70 evidence-based
      guidelines have been set in a rigorous procedure and have been spread via a
      variety of strategies. Knowledge and acceptance of the guidelines in the target
      group is high. In particular, a multifaceted approach with written (scientific
      journal, support materials) and personal approaches (local consensus discussions,
      contact with colleagues, outreach visits by peers) seems to be effective in the
      dissemination. The guideline recommendations are followed in on average 67% of
      the decisions, but there is a large variation between different physicians and
      between different guidelines. Specific strategies designed to handle possible
      obstacles to implementation are needed to improve adherence. Specific
      implementation projects showed the importance of a "diagnostic analysis" of the
      target group and target setting before the start of the implementation.
      CONCLUSIONS: A program to implement a guideline should be well designed, well
      prepared, and preferably pilot tested before use. Such a program should be built
      into the normal channels and structures for improving care. More research into
      the details of implementation is needed to better understand the critical
      determinants of change in practice.

PMID- 11583122
TI  - Implementing practice guidelines for appropriate antimicrobial usage: a
      systematic review.
AB  - BACKGROUND: Antimicrobial resistance is increasing, apparently in part as a
      result of the inappropriate use of antimicrobial agents. OBJECTIVES: To conduct a
      systematic review of guideline implementation studies for improving appropriate
      use of antimicrobial agents and to determine which implementation methods appear
      to improve the outcome of appropriate antimicrobial use. RESEARCH DESIGN: The
      Medline database was searched for comparative studies on guideline implementation
      of appropriate antimicrobial use in common infections. Estimates of treatment
      effects and costs were included. The community-acquired infections selected were
      otitis media, respiratory illnesses, pharyngitis, and sinusitis. The nosocomial
      infections selected were urinary tract infections and surgical wound infections.
      Antiretroviral treatment studies and vancomycin usage studies were also included.
      Other computer-assisted antibiotic control studies not selected in the above
      topics were included. RESULTS: Forty studies were found that documented the
      effectiveness of implementation methods in encouraging appropriate antimicrobial
      use. The available evidence showed that multifaceted implementation methods were
      most successful. Individual implementation methods that appeared to be useful
      were academic detailing, feedback from nurses, pharmacists, or physicians, local
      adaptation of a guideline, small-group interactive sessions, and computer
      assisted care.

PMID- 11583123
TI  - Evaluating an integrated approach to clinical quality improvement: clinical
      guidelines, quality measurement, and supportive system design.
AB  - BACKGROUND: Implementing clinical practice guidelines to change patient outcomes
      presents a challenge. Studies of single interventions focused on changing
      provider behavior demonstrate modest effects, suggesting that effective guideline
      implementation requires a multifaceted approach. Traditional biomedical research
      designs are not well suited to evaluating systems interventions. OBJECTIVES: RAND
      and the Army Medical Department collaborated to develop and evaluate a system for
      implementing guidelines and documenting their effects on patient care. RESEARCH
      DESIGN: The evaluation design blended quality improvement, case study, and
      epidemiologic methods. A formative evaluation of implementation process and an
      outcome evaluation of patient impact were combined. SUBJECTS: Guidelines were
      implemented in 3 successive demonstrations targeting low back pain, asthma, and
      diabetes. This paper reports on the first wave of 4 facilities implementing a low
      back pain guideline. METHODS: Organizational climate and culture, motivation,
      leadership commitment, and resources were assessed. Selected indicators of
      processes and outcomes of care were compared before, during, and after guideline
      implementation at the demonstration facilities and at comparison facilities.
      Logistic regression analysis was used to test for guideline effects on patient
      care. RESULTS: Process evaluation documented varied approaches to quality
      improvement across sites. Outcome evaluation revealed a significant downward
      trend in the percentage of acute low back pain patients referred to physical
      therapy or chiropractic care (10.7% to 7.2%) at demonstration sites and no such
      trend at control sites. CONCLUSIONS: Preliminary results suggest the power of
      this design to stimulate improvements in guideline implementation while retaining
      the power to evaluate rigorously effects on patient care.

PMID- 11583124
TI  - Optimal methods for guideline implementation: conclusions from Leeds Castle
      meeting.
AB  - BACKGROUND: Quality problems in medical care are not a new finding. Variations in
      medical practice as well as actual medical errors have been pointed out for many
      decades. The current movement to write practice guidelines to attempt to correct
      these deviations from recommended medical practice has not solved the problem.
      OBJECTIVE: In order to gain greater acceptance of these guidelines and to change
      the behavior of health care providers, the science of guideline implementation
      must be understood better. RESEARCH DESIGN: A group of experts who have studied
      the problem of implementation in Europe and the United States was convened. This
      meeting summary enumerates the implementation methods studied to date, reviews
      the theories of behavioral change, and makes recommendation for effecting better
      implementation guidelines. RESULTS: A research agenda was proposed to further our
      knowledge of effective evidence-based implementation.

PMID- 11583125
TI  - Comparison of six in-house tests for the rapid diagnosis of feline
      immunodeficiency and feline leukaemia virus infections.
AB  - Six rapid tests for the diagnosis of feline immunodeficiency virus (FIV) and
      feline leukaemia virus (FeLV) infections which have recently been introduced in
      Europe for use in small animal practice were compared. Eight hundred serum
      samples were tested and those reacting FIV-positive in at least one of the tests
      were confirmed by Western blot, and those reacting FeLV-positive were confirmed
      by virus isolation. The specificity and sensitivity of each test and the quality
      of the results produced were compared.

PMID- 11583126
TI  - Analgesia of newborn lambs before castration and tail docking with rubber rings.
AB  - This study assessed the effects of suckled sucrose and parenteral carprofen
      treatment on behavioural measurements of discomfort and serum haptoglobin
      concentration in lambs following rubber ring castration and/or tail docking.
      Twenty-eight male and 20 ewe lambs were allocated to either a male or ewe lamb
      control group (n=4) or to one of three male and two ewe lamb treatment groups
      (n=8). Male lambs in one treatment group received carprofen subcutaneously (0.5
      mg/kg) 30 minutes before castration and docking. Lambs in all other treatment
      groups suckled sucrose or colostrum immediately before castration and/or tail
      docking. Behavioural measurements of discomfort were made following castration or
      tail docking in treatment groups and also in control animals which were not
      castrated or tail docked. Blood sampling of animals in treatment groups for
      analysis of serum haptoglobin, an acute phase protein used as an indicator of an
      acute inflammatory response, was performed before castration or docking and at 24
      and 48 hours after castration or docking. Control lambs were blood sampled at 0,
      24 and 48 hours following behavioural assessment Neither suckled sucrose nor
      carprofen treatment altered discomfort behaviour associated with castration or
      tail docking. Haptoglobin levels following castration or tail docking remained
      close to the detection limits of the assay and were similar to those recorded in
      control animals.

PMID- 11583127
TI  - Comparison of subcutaneous ivermectin and oral moxidectin for the treatment of
      notoedric acariasis in hamsters.
AB  - Thirty hamsters diagnosed with a Notoedres infestation on the basis of their
      clinical signs and skin scrapings were allocated to three matched groups. The
      hamsters in group 1 received ivermectin at 400 microg/kg subcutaneously once a
      week for eight weeks, those in group 2 were treated with moxidectin at 400
      microg/kg orally once a week, and those in group 3 were treated with moxidectin
      at the same dosage, but twice a week. The hamsters' skin lesions were scored
      weekly on the basis of the severity of crusting, erythema, scaling and
      excoriations at various sites. In all three groups the lesion scores were
      significantly lower after four and eight weeks, and there was no significant
      difference between the efficacy of the treatments. However, at the end of the
      treatment, skin scrapings were negative in only 60 to 70 per cent of the animals
      in each group.

PMID- 11583128
TI  - Diffuse splenomegaly caused by splenic abscessation in a dog.

PMID- 11583129
TI  - Incidence and treatment of hydrometra in Canary Island goats.

PMID- 11583130
TI  - Outbreak of diarrhoea and milk drop in cows infected with bovine group B
      rotavirus.

PMID- 11583131
TI  - Amplified fragment length polymorphism differentiation between the vaccine strain
      Chlamydia psittaci 1B and wild field strains.

PMID- 11583132
TI  - Camelostrongylus mentulatus in a roe deer from the Italian Western Alps.

PMID- 11583133
TI  - Training in international animal health.

PMID- 11583134
TI  - Modelling control strategies for foot-and-mouth disease.

PMID- 11583135
TI  - Welfare movement licensing.

PMID- 11583136
TI  - Ethical decision-making in veterinary practice.

PMID- 11583137
TI  - Detection of a circovirus-like agent from farmed pheasants in Italy.

PMID- 11583138
TI  - Controlling stallion behaviour.

PMID- 11583139
TI  - Intestinal disease in dogs.

PMID- 11583140
TI  - Hypertension and chronotherapy: shifting the treatment paradigm.
AB  - The treatment of diseases has been based on the concept of homeostasis and has
      not incorporated an understanding of biologic rhythms and their underlying
      mechanisms. Biologic rhythms are implicated in cardiovascular events. Failure to
      recognize the circadian decline in blood pressure may result in iatrogenic
      chronopathological events, including anterior ischemic optic neuropathy and
      cerebrovascular accidents. Chronotherapeutics is the purposeful alteration of
      drug level to match rhythms to optimize therapeutic outcomes and minimize size
      effects. For the treatment of hypertension, this idea has the potential for a
      therapeutic paradigm shift.

PMID- 11583141
TI  - Circadian rhythms and clinical medicine with applications to hypertension.
AB  - Circadian (24-h) rhythms are important to the practice of medicine. The phasing
      and amplitude of key physiologic and biochemical circadian rhythms contribute to
      predictable-in-time patterns in the manifestation and exacerbation of most
      medical conditions. Moreover, body rhythms can significantly affect responses of
      patients to diagnostic tests and medications. Rhythmicity in the pathophysiology
      of medical conditions is the rationale for chronotherapeutics--that is purposeful
      variance of the concentration of medicines in synchrony with biologic rhythm
      determinants of disease activity--to optimize treatment outcomes. This article
      discusses the concept of biologic time structure and its relevance to the
      practice of medicine, with a focus on hypertension and cardiovascular issues.

PMID- 11583142
TI  - Cyclic and circadian variations in cardiovascular events.
AB  - The incidence of many biologic phenomena displays a reproducible and cyclic
      variation. Cardiovascular disease, the most common cause of death in the United
      States and other developed countries, also has an intrinsic variation in events.
      These events are more common in winter, at the beginning of each month, on
      Mondays (in working people), and during the early morning hours of each day.
      Recent meta-analyses have quantitated the excess risk of cardiovascular events in
      the hours around and just after awakening. Between 6 AM and noon, there is a 40%
      higher risk of heart attack, a 29% increased risk of cardiac death, and a 49%
      increased risk of stroke (compared with what would be expected if these events
      happened at random and were evenly distributed throughout the day). These
      observations have major consequences for emergency medical personnel and medical
      transport systems. The reasons for these observations are less clear. The
      circadian pattern of blood pressure (BP) and heart rate may be a major
      contributor, and long-term "hard end-point" studies designed to test specific
      pharmacologic interventions targeting the early morning rise in BP and heart rate
      are underway. Individuals who work night shifts and those whose BP has a
      different circadian pattern have a higher risk of cardiovascular events, but may
      be less likely to have an increased risk of cardiovascular events in the morning.

PMID- 11583143
TI  - Pharmacology of cardiovascular chronotherapeutic agents.
AB  - Although sudden cardiac death, myocardial infarction, or stroke can occur at any
      time of day, event rates increase during the waking hours, particularly in the
      morning. In most people-both normotensive and hypertensive-blood pressure (BP)
      rises rapidly in the early morning hours, the time when most individuals wake and
      begin their day. This rise in BP corresponds to increased secretion of
      catecholamines and increased plasma renin activity. Thus, vascular tone and total
      peripheral resistance increase in the morning hours, and BP rises as a result. At
      the same time, heart rate increases. In the late morning or early afternoon, BP
      reaches its peak. After that, BP declines, falling 15 to 20 mm Hg between about 8
      PM and 2 AM, the time when BP is usually lowest. These findings have led to an
      interest in chronotherapy for hypertension. A major objective of chronotherapy
      for hypertension is to deliver the drug in higher concentrations during the early
      morning post-awakening period, when BP is highest, and in lesser concentrations
      during the middle of a sleep cycle, when BP is low. Traditional sustained-release
      pharmacologic agents, which deliver a near-constant drug concentration, were not
      designed to complement the circadian pattern. There are currently two
      antihypertensive agents, Verelan PM (verapamil HCl) and Covera HS (verapamil
      HCl), that provide chronotherapy for hypertension. These drugs use novel delivery
      systems that provide 24-h BP control while maximizing drug concentrations in the
      morning and minimizing drug concentrations during sleep.

PMID- 11583144
TI  - Mutations of peripheral myelin protein 22 result in defective trafficking through
      mechanisms which may be common to diseases involving tetraspan membrane proteins.
AB  - Phenotypes of several heritable disorders including forms of hearing loss, myelin
      diseases, hypomagnesemia, and cataracts are linked to missense mutations in
      single alleles encoding membrane proteins having four transmembrane spans. In
      some cases, the mutant proteins exhibit dominant negative or gain-of-function
      behavior whereby heterozygous coexpression of mutant and wild-type genes leads to
      more serious pathology than is the case for individuals in which only a single
      wild-type allele is expressed. An example is found in the relationship of
      peripheral myelin protein 22 (PMP22) to Charcot-Marie-Tooth disease (CMTD) type
      1A. A number of disease-linked PMP22 mutants fail to undergo normal trafficking
      beyond the endoplasmic reticulum or intermediate compartment to reach the cell
      surface. Moreover, recent evidence suggests that pathology resulting from this
      mistrafficking-based loss of function may also be augmented by the ability of
      some mutants to disrupt normal trafficking of the product of the wild-type PMP22
      allele. The basis for this phenomenon appears to be the heterodimerization of
      trafficking-incompetent mutants with wild-type PMP22, such that both the wild
      type protein and the mutant forms are retained early in the secretory pathway.
      The full cellular and structural biological details of these observations remain
      to be elucidated. However, the model suggested by the existing data regarding the
      relationship of PMP22 to CMTD may be useful to explain phenotypes of several
      other diseases involving other tetraspan membrane proteins and to facilitate
      predictions regarding previously undetected disease-protein linkages.

PMID- 11583145
TI  - Protein interactions leading to conformational changes monitored by limited
      proteolysis: apo form and fragments of horse cytochrome c.
AB  - Proteolysis experiments have been used to monitor the conformational transitions
      from an unfolded to a folded state occurring when the apo form of horse
      cytochrome c (cyt c) binds the heme moiety or when two fragments of cyt c form a
      native-like 1:1 complex. Proteinase K was used as a proteolytic probe, in view of
      the fact that the broad substrate specificity of this protease allows digestion
      at many sites along a polypeptide chain. The rather unfolded apo form of cyt c
      binds heme with a concomitant conformational transition to a folded species
      characterized by an enhanced content of helical secondary structure. While the
      holoprotein is fully resistant to proteolytic digestion and the apoprotein is
      digested to small peptides, the noncovalent complex of the apoprotein and heme
      exhibits an intermediate resistance to proteolysis, in agreement with the fact
      that the more folded structure of the complex makes the protein substrate more
      resistant to proteolysis. The noncovalent native-like complex of the two
      fragments 1-56 and 57-104 of cyt c, covering the entire polypeptide chain of 104
      residues of the protein, is rather resistant to proteolysis, while the individual
      fragments are easily digested. Fragment 57-104 is fast degraded to several
      peptides, while fragment 1-56 is slowly degraded stepwise from its C-terminal
      end, leading initially mostly to fragments 1-48 and 1-40 and, at later stages of
      proteolysis, fragments 1-38, 1-35, 1-33, and 1-31. Thus, proteolysis data
      indicate that the heme containing fragment 1-56 has a rather compact core and a C
      terminal flexible tail. Upon prolonged incubation of the complex of fragments 1
      56 and 57-104 (nicked cyt c) with proteinase K, a chain segment is removed from
      the nicked protein, leading to a gapped protein complex of fragments of 1-48 and
      57-104 and, on further digestion, fragments 1-40 and 57-104. Of interest, the
      chain segment being removed by proteolysis of the complex matches the omega-loop
      which is evolutionarily removed in cyt c of microbial origin. Overall, rates
      and/or resistance to proteolysis correlates well with the extent of folding of
      the protein substrates, as deduced from circular dichroism measurements. Thus,
      our results underscore the utility of proteolytic probes for analyzing
      conformational and dynamic features of proteins. Finally, a specific interest of
      the cyt c fragment system herewith investigated resides in the fact that the
      fragments are exactly the exon products of the cyt c gene.

PMID- 11583146
TI  - Probing the differences between rat liver outer mitochondrial membrane cytochrome
      b5 and microsomal cytochromes b5.
AB  - Two distinct forms of cytochrome b5 exist in the rat hepatocyte. One is
      associated with the membrane of the endoplasmic reticulum (microsomal, or Mc, cyt
      b5) while the other is associated with the outer membrane of liver mitochondria
      (OM cyt b5). Rat OM cyt b5, the only OM cyt b5 identified so far, has a
      significantly more negative reduction potential and is substantially more stable
      toward chemical and thermal denaturation than Mc cytochromes b5. In addition,
      hemin is kinetically trapped in rat OM cyt b5 but not in the Mc proteins. As a
      result, no transfer of hemin from rat OM cyt b5 to apomyoglobin is observed at pH
      values as low as 5.2, nor can the thermodyamically favored ratio of hemin
      orientational isomers be achieved under physiologically relevant conditions.
      These differences are striking given the similarity of the respective protein
      folds. A combined theoretical and experimental study has been conducted in order
      to probe the structural basis behind the remarkably different properties of rat
      OM and Mc cytochromes b5. Molecular dynamics (MD) simulations starting from the
      crystal structure of bovine Mc cyt b5 revealed a conformational change that
      exposes several internal residues to the aqueous environment. The new
      conformation is equivalent to the "cleft-opened" intermediate observed in a
      previously reported MD simulation of bovine Mc cyt b5 [Storch, E. M., and
      Daggett, V. (1995) Biochemistry 34, 9682-9693]. The rat OM protein does not adopt
      a comparable conformation in MD simulations, thus restricting access of water to
      the protein interior. Subsequent comparisons of the protein sequences and
      structures suggested that an extended hydrophobic network encompassing the side
      chains of Ala-18, Ile-32, Leu-36, and Leu-47 might contribute to the inability of
      rat OM cyt b5 to adopt the cleft-opened conformation and, hence, stabilize its
      fold relative to the Mc isoforms. A corresponding network is not present in
      bovine Mc cyt b5 because positions 18, 32, and 47, are occupied by Ser, Leu, and
      Arg, respectively. To probe the roles played by Ala-18, Ile-32, and Leu-47 in
      endowing rat OM cyt b5 with its unusual structural properties, we have replaced
      them with the corresponding residues in bovine Mc cyt b5. Hence, the I32L
      (single), A18S/L47R (double), and A18S/L47R/I32L (triple) mutants of rat OM cyt
      b5 were prepared. The stability of these proteins was found to decrease in the
      following order: WT rat OM > rat OM I32L > rat OM A18S/L47R > rat OM
      A18S/L47R/I32L > bovine Mc cyt b5. The decrease in stability of the rat OM
      protein correlates with the extent to which the hydrophobic cluster involving the
      side chains of residues 18, 32, 36, and 47 has been disrupted. Complete
      disruption of the hydrophobic network in the triple mutant is confirmed in a 2.0
      A resolution crystal structure of the protein. Disruption of the hydrophobic
      network also facilitates hemin loss at pH 5.2 for the double and triple mutants,
      with the less stable triple mutant exhibiting the greater rate of hemin transfer
      to apomyoglobin. Finally, 1H NMR spectroscopy and side-by-side comparisons of the
      crystal structures of bovine Mc, rat OM, and rat OM A18S/L47R/I32L cyt b5 allowed
      us to conclude that the nature of residue 32 plays a key role in controlling the
      relative stability of hemin orientational isomers A and B in rat OM cyt b5. A
      similar analysis led to the conclusion that Leu-70 and Ser-71 play a pivotal role
      in stabilizing isomer A relative to isomer B in Mc cytochromes b5.

PMID- 11583147
TI  - The structural basis for substrate specificity and inhibition of human S
      adenosylmethionine decarboxylase.
AB  - S-Adenosylmethionine decarboxylase belongs to a small class of amino acid
      decarboxylases that use a covalently bound pyruvate as a prosthetic group. It is
      an essential enzyme for polyamine biosynthesis and provides an important target
      for the design of anti-parasitic and cancer chemotherapeutic agents. We have
      determined the structures of S-adenosylmethionine decarboxylase complexed with
      the competitive inhibitors methylglyoxal bis(guanylhydrazone) and 4-amidinoindan
      1-one-2'-amidinohydrazone as well as the irreversible inhibitors 5'-deoxy-5'-[N
      methyl-N-[(2-aminooxy)ethyl]amino]adenosine, 5'-deoxy-5'-[N-methyl-N-(3
      hydrazinopropyl)amino]adenosine, and the methyl ester analogue of S
      adenosylmethionine. These structures elucidate residues important for substrate
      binding and show how those residues interact with both covalently and
      noncovalently bound inhibitors. S-Adenosylmethionine decarboxylase has a four
      layer alphabeta betaalpha sandwich fold with residues from both beta-sheets
      contributing to substrate and inhibitor binding. The side chains of conserved
      residues Phe7, Phe223, and Glu247 and the backbone carbonyl of Leu65 play
      important roles in binding and positioning the ligands. The catalytically
      important residues Cys82, Ser229, and His243 are positioned near the methionyl
      group of the substrate. One molecule of putrescine per monomer is observed
      between the two beta-sheets but far away from the active site. The activating
      effects of putrescine may be due to conformational changes in the enzyme, to
      electrostatic effects, or both. The adenosyl moiety of the bound ligand is
      observed in the unusual syn conformation. The five structures reported here
      provide a framework for interpretation of S-adenosylmethionine decarboxylase
      inhibition data and suggest strategies for the development of more potent and
      more specific inhibitors of S-adenosylmethionine decarboxylase.

PMID- 11583148
TI  - Structure of a human S-adenosylmethionine decarboxylase self-processing ester
      intermediate and mechanism of putrescine stimulation of processing as revealed by
      the H243A mutant.
AB  - S-Adenosylmethionine decarboxylase (AdoMetDC) is synthesized as a proenzyme that
      cleaves itself in a putrescine-stimulated reaction via an N-->O acyl shift and
      beta-elimination to produce an active enzyme with a catalytically essential
      pyruvoyl residue at the new N-terminus. N-->O acyl shifts initiate the self
      processing of other proteins such as inteins and amidohydrolases, but their
      mechanisms in such proteins are not well understood. We have solved the crystal
      structure of the H243A mutant of AdoMetDC to 1.5 A resolution. The mutant protein
      is trapped in the ester form, providing clear evidence for the structure of the
      ester intermediate in the processing of pyruvoyl enzymes. In addition, a
      putrescine molecule is bound in a charged region within the beta-sandwich, and
      cross-links the two beta-sheets through hydrogen bonds to several acidic residues
      and ordered water molecules. The high-resolution structure provides insight into
      the mechanism for the self-processing reaction and provides evidence for the
      mechanism for simulation of the self-processing reaction by putrescine. Studies
      of the effects of putrescine or 4-aminobutanol on the processing of mutant
      AdoMetDC proenzymes are consistent with a model in which a single activator
      molecule interacts with buried Asp174, Glu178, and Glu256, leading to an
      alteration in the position of Glu11, resulting in stimulation of self-processing.

PMID- 11583149
TI  - The beta7-beta8 loop of the p51 subunit in the heterodimeric (p66/p51) human
      immunodeficiency virus type 1 reverse transcriptase is essential for the
      catalytic function of the p66 subunit.
AB  - The heterodimeric human immunodeficiency virus type 1 reverse transcriptase (HIV
      1 RT) is composed of p66 and p51 subunits, p66 being the catalytic subunit. Our
      earlier investigation on the role of p51 in the catalytic process has shown that
      the p51 subunit facilitates the loading of the p66 subunit onto the template
      primer (TP). We had postulated that the beta7-beta8 loop of the p51 subunit may
      be involved in opening the polymerase cleft of p66 for DNA binding [Pandey, V.
      N., et al. (1996) Biochemistry 35, 2168]. We report here that deletion or alanine
      substitution of four residues of the beta7-beta8 loop results in severe
      impairment of the polymerase function of the heterodimeric enzyme. The enzyme
      activity was restored to the wild-type levels when the mutant p66 subunit was
      dimerized with the wild-type p51, suggesting that the intact beta7-beta8 loop in
      the p51 subunit is indispensable for the catalytic function of p66. Further, the
      template primer binding ability of the enzyme was significantly reduced upon
      deletion or alanine substitution in the beta7-beta8 loop. Interestingly, the loss
      of the TP binding ability of the mutant p66 was restored upon dimerization with
      wild-type p51. Examination of the glycerol gradient ultracentrifugation analysis
      revealed that while the wild-type HIV-1 RT sediments as a dimeric protein, the
      mutant enzymes carrying deletion or alanine substitution in both the subunits
      sediment predominantly as monomeric proteins, suggesting their inability to form
      stable dimers. In contrast, mutant p66 dimerized with wild-type p51
      (p66delta/p51WT and p66Ala/p51WT) sedimented at the dimeric position. Taken
      together, these results clearly implicate the importance of the beta7-beta8 loop
      of p51 in the formation of stable functional heterodimers.

PMID- 11583150
TI  - Selection and characterization of a new class of peptide exosite inhibitors of
      coagulation factor VIIa.
AB  - A new series of peptide inhibitors of human Factor VIIa (FVIIa) has been
      identified and affinity matured from naive and partially randomized peptide phage
      libraries selected against the immobilized tissue factor x Factor VIIa (TF x
      FVIIa) complex. These "A-series" peptides contain a single disulfide bond and a
      13-residue minimal core required for maximal affinity. They are exemplified by
      peptide A-183 (EEWEVLCWTWETCER), which binds at a newly identified exosite on the
      FVIIa protease domain, described in the accompanying report [Roberge, M.,
      Santell, L., Dennis, M. S., Eigenbrot, C., Dwyer, M. A., and Lazarus, R. A.
      (2001) Biochemistry 40, 9522-9531]. A-183 was obtained from a trypsin digest of A
      100-Z, a recombinant protein comprising A-183 and the Z domain of protein A.
      Surprisingly, A-183 was a very potent inhibitor of TF x FVIIa, inhibiting
      activation of Factor X (FX) and Factor IX and amidolytic activity of Chromozym t
      PA with IC50 values of 1.6 +/- 1.2, 3.5 +/- 0.3, and 8.5 +/- 3.5 nM,
      respectively. Kinetic analysis revealed that A-183 was a partial (hyperbolic)
      mixed-type inhibitor of FX activation having a Ki of 200 pM as well as a partial
      competitive inhibitor of amidolytic activity. The A-series peptides were also
      specific and potent inhibitors of TF-dependent clotting as measured in a
      prothrombin time (PT) clotting assay and had no effect on the TF-independent
      activated partial thromboplastin time. At saturating concentrations of peptide,
      the maximal extent by which A-183 and A-100-Z inhibited the rate of FX activation
      was 78 +/- 3 and 89 +/- 6%, respectively. The degree of inhibition of the rate of
      FX activation correlated with a maximum fold prolongation in the PT assay of 1.8
      fold for A- 183 and 3.3-fold for A-100-Z. The A-series peptides represent a new
      class of peptide exosite inhibitors that are capable of attenuating, rather than
      completely inhibiting, the activity of TF x FVIIa, potentially leading to
      anticoagulants with an increased therapeutic window.

PMID- 11583151
TI  - A novel exosite on coagulation factor VIIa and its molecular interactions with a
      new class of peptide inhibitors.
AB  - A new inhibitory peptide binding exosite on the protease domain of coagulation
      Factor VIIa (FVIIa) has been identified. A novel series of peptide inhibitors of
      FVIIa, termed the "A-series" peptides, identified from peptide phage libraries
      and exemplified by peptide A-183 [Dennis, M. S., Roberge, M., Quan, C., and
      Lazarus, R. A. (2001) Biochemistry 40, 9513-9521], specifically bind at a site
      that is distinct from both the active site and the exosite of another recently
      described peptide inhibitor of FVIIa, E-76 [Dennis, M. S., Eigenbrot, C.,
      Skelton, N. J., Ultsch, M. H., Santell, L., Dwyer, M. A., O'Connell, M. P., and
      Lazarus, R. A. (2000) Nature 404, 465-4701. Peptide A-183 prolonged TF-dependent
      clotting in human, but not rabbit plasma. Thus, a panel of human FVIIa mutants,
      containing 70 of the 76 rabbit sequence differences in the protease domain,
      localized the binding site to residues in the 60s loop and the C-terminus. The
      location of the exosite was refined by a series of FVIIa alanine mutants, which
      showed that proximal residues Trp 61 and Leu 251 were critical for binding.
      Kinetic and equilibrium binding constants for zymogen FVII, FVIIa and TF x FVIIa
      were determined using immobilized N-terminal biotinylated A-183 by surface
      plasmon resonance. No peptide binding to nine other human serine proteases was
      observed. Key residues on the peptide were determined from binding to FVIIa and
      inhibition of FX activation using a series of alanine mutants of A-183 fused to
      the Z domain of protein A. Analysis of the mutagenesis data is presented in the
      context of a crystal structure of A-183 in complex with a version of zymogen FVII
      [Eigenbrot, C., Kirchhofer, D., Dennis, M. S., Santell, L., Lazarus, R. A.,
      Stamos, J., and Ultsch, M. H. (2001) Structure 9, 627-636]. The shape and
      proximity of this exosite to the active site may lend itself towards the design
      of new anticoagulants that inhibit FVIIa.

PMID- 11583152
TI  - Benign synthesis of 2-ethylhexanoic acid by cytochrome P450cam: enzymatic,
      crystallographic, and theoretical studies.
AB  - This study examines the ability of P450cam to catalyze the formation of 2
      ethylhexanoic acid from 2-ethylhexanol relative to its activity on the natural
      substrate camphor. As is the case for camphor, the P450cam exhibits
      stereoselectivity for binding (R)- and (S)-2-ethylhexanol. Kinetic studies
      indicate (R)-2-ethylhexanoic acid is produced 3.5 times as fast as the (S)
      enantiomer. In a racemic mixture of 2-ethylhexanol, P450cam produces 50% more (R)
      2-ethylhexanoic acid than (S)-2-ethylhexanoic acid. The reason for
      stereoselective 2-ethylhexanoic acid production is seen in regioselectivity
      assays, where (R)-2-ethylhexanoic acid comprises 50% of total products while (S)
      2-ethylhexanoic acid comprises only 13%. (R)- and (S)-2-ethylhexanol exhibit
      similar characteristics with respect to the amount of oxygen and reducing
      equivalents consumed, however, with (S)-2-ethylhexanol turnover producing more
      water than the (R)-enantiomer. Crystallographic studies of P450cam with (R)- or
      (S)-2-ethylhexanoic acid suggest that the (R)-enantiomer binds in a more ordered
      state. These results indicate that wild-type P450cam displays stereoselectivity
      toward 2-ethylhexanoic acid synthesis, providing a platform for rational active
      site design.

PMID- 11583153
TI  - Residues in Methylosinus trichosporium OB3b methane monooxygenase component B
      involved in molecular interactions with reduced- and oxidized-hydroxylase
      component: a role for the N-terminus.
AB  - Methane monooxygenase (MMO) is a non-heme-iron-containing enzyme which consists
      of 3 protein components: a hydroxylase (MMOH), an NAD(P)H-linked reductase
      (MMOR), and a 138-residue regulatory protein, component B (MMOB). Here, NMR
      spectroscopy has been used to derive interactions between MMOB and reduced and
      oxidized states of MMOH (245 kDa). Differential broadening of MMOB resonances in
      1H-15N HSQC spectra acquired at different molar ratios of MMOH indicates
      interaction of both proteins, with MMOB binding more tightly to oxidized MMOH as
      observed previously. The most broadened backbone NH resonances suggest which
      residues in MMOB are part of the MMOH-binding interface, particularly when those
      residues are spatially close or clustered in the structure of MMOB. Although a
      number of different residues in MMOB appear to be involved in interacting with
      oxidized- and reduced-MMOH, some are identical. The two most common segments,
      proximal in the structure of MMOB, are beta-strand 1 with turn 1 (residues 36-46)
      and alpha-helix 3 going into loop 2 (residues 101-112). In addition, the N
      terminus of MMOB is observed to be involved in binding to MMOH in either redox
      state. This is most strongly evidenced by use of a synthetic N-terminal peptide
      from MMOB (residues 1-29) in differential broadening 1H TOCSY studies with MMOH.
      Binding specificity is demonstrated by displacement of the peptide from MMOH by
      parent MMOB, indicating that the peptide binds in or near the normal site of N
      terminal binding. The N-terminus is also observed to be functionally important.
      Steady-state kinetic studies show that neither a delta2-29 MMOB deletion mutant
      (which in fact does bind to MMOH), the N-terminal peptide, nor a combination of
      the two elicit the effector functions of MMOB. Furthermore, transient kinetic
      studies indicate that none of the intermediates of the MMOH catalytic cycle are
      observed if either the delta2-29 MMOB mutant or the N-terminal peptide is used in
      place of MMOB, suggesting that deletion of the N-terminus prevents reaction of
      reduced MMOH with O2 that initiates catalysis.

PMID- 11583154
TI  - High-resolution solution structure of human intestinal trefoil factor and
      functional insights from detailed structural comparisons with the other members
      of the trefoil family of mammalian cell motility factors.
AB  - The secreted proteins intestinal trefoil factor (ITF, 59 residues), pS2 (60
      residues), and spasmolytic polypeptide (SP, 106 residues) form a small family of
      trefoil domain-containing mammalian cell motility factors, which are essential
      for the maintenance of all mucous-coated epithelial surfaces. We have used 1H NMR
      spectroscopy to determine the high-resolution structure of human ITF, which has
      allowed detailed structural comparisons with the other trefoil cell motility
      factors. The conformation of residues 10-53 of hITF is determined to high
      precision, but the structure of the N- and C-terrminal residues is poorly defined
      by the NMR data, which is probably indicative of significant mobility. The core
      of the trefoil domain in hITF consists of a two-stranded antiparallel beta-sheet
      (Cys 36 to Asp 39 and Trp 47 to Lys 50), which is capped by an irregular loop and
      forms a central hairpin (loop 3). The beta-sheet is preceded by a short alpha
      helix (Lys 29 to Arg 34), with the majority of the remainder of the domain
      contained in two loops formed from His 25 to Pro 28 (loop 2) and Ala 12 to Arg 18
      (loop 1), which lie on either side of the central hairpin. The region formed by
      the surface of loop 2, the cleft between loop 2 and loop 3, and the adjacent face
      of loop 3 has previously been proposed to form the functional site of trefoil
      domains. Detailed comparisons of the backbone conformations and surface features
      of the family of trefoil cell motility factors (porcine SP, pS2, and hITF) have
      identified significant structural and electrostatic differences in the loop
      2/loop 3 regions, which suggest that each trefoil protein has a specific target
      or group of target molecules.

PMID- 11583155
TI  - Dynamics of a de novo designed three-helix bundle protein studied by 15N, 13C,
      and 2H NMR relaxation methods.
AB  - Understanding how the amino acid sequence of a polypeptide chain specifies a
      unique, functional three-dimensional structure remains an important goal,
      especially in the context of the emerging discipline of de novo protein design.
      Alpha3D is a single chain protein of 73 amino acids resulting from a de novo
      design effort. Previous solution nuclear magnetic resonance studies of alpha3D
      confirm that the protein adopts the designed structure of a three-helix bundle.
      Furthermore, alpha3D has been previously shown to possess all of the major
      thermodynamic and structural characteristics of natural proteins, though it
      shares no sequence homology to any protein sequence in the database. In this
      work, the backbone and side-chain dynamics of alpha3D were investigated using
      15N, 13C, and 2H nuclear magnetic resonance relaxation methods with the aim of
      assessing the character of the internal motions of this native-like protein of de
      novo design. At the backbone level, both 15N and 13C(alpha) relaxation studies
      indicate highly restrictive motion on the picosecond to nanosecond time scale in
      the alpha-helical regions of alpha3D, with increasing mobility at the ends of the
      alpha-helices and in the two loop regions. This is largely consistent with what
      is seen in proteins of natural origin. Overall, the view provided by both 2H and
      13C methyl relaxation methods suggest that the side chains of alpha3D are more
      dynamic compared to natural proteins. Regions of relative flexibility bound
      clusters of rigid methyl-bearing side-chain groups that are interspersed with
      aromatic and beta-branched amino acids. The time scale of motions associated with
      methyl-bearing side chains of alpha3D are significantly longer than that seen in
      natural proteins. These results indicate that the strategies underlying the
      design of alpha3D have largely, but not completely, captured both the structural
      and dynamic character of natural proteins.

PMID- 11583156
TI  - The membrane-proximal tryptophan-rich region of the HIV glycoprotein, gp41, forms
      a well-defined helix in dodecylphosphocholine micelles.
AB  - The membrane-proximal tryptophan-rich region of the HIV transmembrane
      glycoprotein, gp41, plays an important role in the membrane fusion reaction.
      Using NMR spectroscopy, we have studied the tertiary structure of a synthetic 19
      residue amidated peptide (NH2-KWASLWNWFNITNWLWYIK-CONH2) corresponding to this
      region in membrane-mimetic environments. Initial experiments in sodium dodecyl
      sulfate/H2O micelles and trifluoroethanol gave poor results, because of low
      solubility. However, in dodecylphosphocholine micelles, we obtained excellent 500
      and 800 MHz NMR spectra, suggesting that the peptide has a preference for a
      zwitterionic membrane-like environment. The final NMR structures demonstrated a
      well-defined helical peptide with a backbone rmsd of 0.47 +/- 0.18 A. Four of the
      five tryptophan residues, as well as the tyrosine residue, formed a "collar" of
      aromatic residues along the axial length of the helix. By analogy to related
      tryptophan-rich antimicrobial peptides, the structure indicates that the aromatic
      residues of the HIV peptide are positioned within the membrane-water interface of
      a phospholipid bilayer. This is confirmed by the observation of direct NOEs
      between the aromatic residues of the peptide to the headgroup and interfacial
      protons of prototonated dodecylphosphocholine. The bulk of the polar residues are
      positioned on one face of this structure, with the hydrophobic phenylalanine side
      chain on the opposing face, forming an amphipathic structure. This work shows
      that the Trp-rich membrane-proximal region of HIV and related viruses can bind to
      the surfaces of zwitterioninc membranes in a "Velcro-like" manner.

PMID- 11583157
TI  - Effect of the central disulfide bond on the unfolding behavior of elongation
      factor Ts homodimer from Thermus thermophilus.
AB  - Functionally active elongation factor Ts (EF-Ts) from Thermus thermophilus forms
      a homodimer. The dimerization interface of EF-Ts is composed of two antiparallel
      beta-sheets that can be connected by an intermolecular disulfide bond. The
      stability of EF-Ts from T. thermophilus in the presence and absence of the
      intermolecular disulfide bond was studied by differential scanning calorimetry
      and circular dichroism. The ratio of the van't Hoff and calorimetric enthalpies,
      delta H(vH)/delta H(cal), indicates that EF-Ts undergoes thermal unfolding as a
      dimer independently of the presence or absence of the disulfide bond. This can be
      concluded from (1) the presence of residual secondary structure above the thermal
      transition temperature, (2) the absence of concentration dependence, which would
      be expected for dissociation of the dimer prior to unfolding of the monomers, and
      (3) a relatively low heat capacity change (delta Cp) upon unfolding. The retained
      dimeric structure of the thermally denatured state allowed for the determination
      of the effect of the intermolecular disulfide bond on the conformational
      stability of EF-Ts, which is deltadelta G(S-S,SH HS) = 10.5 kJ/mol per monomer at
      72.5 degrees C. The possible physiological implications of the dimeric EF-Ts
      structure and of the intersubunit disulfide bond for the extreme conformational
      stability of proteins in thermophiles are discussed.

PMID- 11583158
TI  - Three-dimensional folding of the tRNA-like domain of Escherichia coli tmRNA.
AB  - UV irradiation of Escherichia coli tmRNA both on and off the ribosome induced
      covalent cross-links between its 3'- and its 5'-terminal segments. Cross-linking
      was unaffected in a molecule that lacked the tag-peptide codon region and
      pseudoknots 2, 3, and 4. Intact and truncated cross-linked tmRNAs were
      aminoacylated as efficiently as the respective nonirradiated molecules,
      suggesting that the added UV-induced bonds did not disturb tmRNA conformation.
      Using RNase H digestion followed by primer extension with reverse transcriptase,
      two cross-linked sites were identified within the tRNA-like region of tmRNA. The
      first was formed between nucleotides U9/U10 near the 5' end and nucleotides
      C346/U347 in the T loop. The second cross-link involved residues at positions 25
      28 and 326-329 within helix 2a. Together with comparative sequence analysis,
      these findings yielded a three-dimensional model of the tRNA-like domain of E.
      coli tmRNA. Despite significant reduction of the D domain and the proximity of
      U9/U10 and C346/U347, the model closely resembles the L-shaped structure of
      canonical tRNA.

PMID- 11583159
TI  - Application of cross-correlated NMR spin relaxation to the zinc-finger protein
      CRP2(LIM2): evidence for collective motions in LIM domains.
AB  - The solution structure of quail CRP2(LIM2) was significantly improved by using an
      increased number of NOE constraints obtained from a 13C,15N-labeled protein
      sample and by applying a recently developed triple-resonance cross-correlated
      relaxation experiment for the determination of the backbone dihedral angle psi.
      Additionally, the relative orientation of the 15N(i)-1HN(i) dipole and the
      13CO(i) CSA tensor, which is related to both backbone angles phi and psi, was
      probed by nitrogen-carbonyl multiple-quantum relaxation and used as an additional
      constraint for the refinement of the local geometry of the metal-coordination
      sites in CRP2(LIM2). The backbone dynamics of residues located in the folded part
      of CRP2(LIM2) have been characterized by proton-detected 13C'(i-1)-15N(i) and
      15N(i)-1HN(i) multiple-quantum relaxation, respectively. We show that regions
      having cross-correlated time modulation of backbone isotropic chemical shifts on
      the millisecond to microsecond time scale correlate with residues that are
      structurally altered in the mutant protein CRP2(LIM2)R122A (disruption of the
      CCHC zinc-finger stabilizing side-chain hydrogen bond) and that these residues
      are part of an extended hydrogen-bonding network connecting the two zinc-binding
      sites. This indicates the presence of long-range collective motions in the two
      zinc-binding subdomains. The conformational plasticity of the LIM domain may be
      of functional relevance for this important protein recognition motif.

PMID- 11583160
TI  - Mutation of Tyr138 disrupts the structural coupling between the opposing domains
      in vertebrate calmodulin.
AB  - We have used circular dichroism and frequency-domain fluorescence spectroscopy to
      determine how the site-specific substitution of Tyr138 with either Phe138 or
      Gln138 affects the structural coupling between the opposing domains of calmodulin
      (CaM). A double mutant was constructed involving conservative substitution of
      Tyr99 --> Trp99 and Leu69 --> Cys69 to assess the structural coupling between the
      opposing domains, as previously described [Sun, H., Yin, D., and Squier, T. C.
      (1999) Biochemistry 38, 12266-12279]. Trp99 acts as a fluorescence resonance
      energy transfer (FRET) donor in distance measurements to probe the conformation
      of the central helix. Cys69 provides a reactive group for the covalent attachment
      of 5-((((2-iodoacetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid (IAEDANS),
      which functions as a FRET acceptor and permits the measurement of the rotational
      dynamics of the amino-terminal domain. These CaM mutants demonstrate normal
      calcium-dependent gel-mobility shifts and changes in their near-UV CD spectra,
      have similar secondary structures to wild-type CaM following calcium activation,
      and retain the ability to fully activate the plasma membrane Ca-ATPase. The
      global folds, therefore, of both the carboxyl- and amino-terminal domains in
      these CaM mutants are similar to that of wild-type CaM. However, in comparison to
      wild-type CaM, the substitution of Tyr138 with either Phe138 or Gln138 results in
      (i) alterations in the average spatial separation and increases in the
      conformational heterogeneity between the opposing globular domains and (ii) the
      independent rotational dynamics of the amino-terminal domain. These results
      indicate that alterations in either the hydrogen bond between Tyr138 and Glu82 or
      contact interactions between aromatic amino acid side chains have the potential
      to initiate the structural collapse of CaM normally associated with target
      protein binding and activation.

PMID- 11583161
TI  - Interpretation of the reversible inhibition of adenosine deaminase by small
      cosolutes in terms of molecular crowding.
AB  - Published results on the inhibitory effects of small cosolutes on adenosine
      deamination by adenosine deaminase [Kurz, L. C., Weitkamp, E., and Frieden, C.
      (1987) Biochemistry 26, 3027-3032; Dzingeleski, G., and Wolfenden, R. (1993)
      Biochemistry 32, 9143-9147] have been reexamined. Results for sucrose, dioxane,
      methanol, and ethanol are shown to be qualitatively consistent with thermodynamic
      interpretation in terms of molecular crowding effects arising from the occurrence
      of a minor increase in enzyme volume and/or asymmetry during the kinetic reaction
      -a conformational transition that could be either preexisting or ligand induced.
      Direct evidence for the existence of the putative isomeric transition is provided
      by active enzyme gel chromatography on Sephadex G-100, which demonstrates a
      negative dependence of enzyme elution volume upon substrate concentration and is
      therefore consistent with substrate-mediated conformational changes that favor a
      larger (or more asymmetric) isomeric state of the enzyme. There are thus
      experimental grounds for adopting the present description of the inhibitory
      effects of unrelated cosolutes on the kinetics of adenosine deamination by
      adenosine deaminase in terms of thermodynamic nonideality.

PMID- 11583162
TI  - A two-process model describes the hydrogen exchange behavior of cytochrome c in
      the molten globule state with various extents of acetylation.
AB  - Acetylation of Lys residues of horse cytochrome c steadily stabilizes the molten
      globule state in 18 mM HCl as more Lys residues are acetylated [Goto and
      Nishikiori (1991) J. Mol. Biol. 222, 679-686]. The dynamic features of the molten
      globule state were characterized by hydrogen/deuterium exchange of amide protons,
      monitored by mass spectrometry as each deuteration increased the protein mass by
      1 Da. Electrospray mass spectrometry enabled us to monitor simultaneously the
      exchange kinetics of more than seven species with a different number of acetyl
      groups. One to four Lys residue-acetylated cytochrome c showed almost no
      protection of the amide protons from rapid exchange. The transition from the
      unprotected to the protected state occurred between five and eight Lys residue
      acetylated species. For species with more than nine acetylated Lys residues, the
      exchange kinetics were independent of the extent of acetylation, and 26 amide
      protons were protected at 60 min of exchange, indicating the formation of a rigid
      hydrophobic core with hydrogen-bonded secondary structures. The apparent
      transition to the protected state required a higher degree of acetylation than
      the conformational transition measured by circular dichroism, which had a
      midpoint at about four acetylated residues. This difference in the transitions
      suggested a two-process model in which the exchange occurs either from the
      protected folded state or from the unprotected unfolded state through global
      unfolding. On the basis of a two-process model and with the reported values of
      the exchange and stability parameters, we simulated the exchange kinetics of a
      series of acetylated cytochrome c species. The simulated kinetics reproduced the
      observed kinetics well, indicating validity of this model for hydrogen exchange
      of the molten globule state.

PMID- 11583163
TI  - Kinetics in the pre-steady state of the formation of cystines in ribonucleoside
      diphosphate reductase: evidence for an asymmetric complex.
AB  - Two folded polypeptides, designated R1 and R2, respectively, combine in an as yet
      undefined stoichiometry to form ribonucleoside diphosphate reductase
      (ribonucleotide reductase) from Escherichia coli. Two pairs of cysteines in each
      R1 protomer have been implicated in the enzymatic mechanism. One pair, cysteines
      225 and 462, is located in the active site of the enzyme and forms a cystine
      concomitant with the reduction of the ribonucleotide. The other pair, cysteines
      754 and 759, is located near the carboxy terminus and is thought to reduce the
      cystine in the active site by disulfide interchange; either thioredoxin or
      glutaredoxin is then thought to reduce the cystine that results. Rapid quenching
      and site-directed immunochemistry have been used to follow the formation of the
      cystine in the active site and the peripheral cystine simultaneously during the
      pre-steady state. Prereduced R1 dimer of ribonucleoside diphosphate reductase, in
      the presence of ATP and CDP, was mixed with R2 dimer in an apparatus for quench
      flow. The reaction was quenched with a solution of acetic acid and N
      ethylmaleimide, the protein was then precipitated with trichloroacetic acid, and
      the precipitate was separated into two portions. The percent of the cystine in
      the active site in one of the portions was determined as described previously
      [Erickson, H. K. (2000) Biochemistry 39, 9241-9250]. A similar method was
      employed to determine the percent of the peripheral cystine in the other portion
      of the precipitate. It was found that while the formation of both of these
      cystines was initiated by the addition of R2 dimer, presumably as products of the
      reduction of CDP, the peripheral cystine appeared to form more rapidly and in a
      higher yield than the cystine in the active site. These results demonstrate that
      the formation of the cystine between cysteines 754 and 759 of ribonucleotide
      reductase from E. coli is kinetically competent. A mechanism consistent with the
      prior formation of the cystine between cysteine 225 and cystene 462 as well as
      the kinetics for the formation of each cystine with time is presented. Because
      twice as much of the peripheral cystine than cystine in the active site had
      formed during the pre-steady state, it follows that the enzymatically competent
      complex between R1 dimers and R2 dimers cannot be symmetric.

PMID- 11583164
TI  - DNA length-dependent cooperative interactions in the binding of Ku to DNA.
AB  - Despite its central role in the nonhomologous DNA end joining process, we still
      have an incomplete picture of the interaction between Ku and DNA. Here we
      describe both kinetic (surface plasmon resonance or SPR) and equilibrium
      (electrophoretic mobility shift assay or EMSA) studies of Ku binding to linear
      double-stranded DNA. Ku interaction with 1-site DNA is noncooperative, as
      expected. Electrophoretic mobility shift assays indicate cooperativity in the
      binding of Ku molecules to DNA long enough for two Ku molecules to bind (2-site
      DNA). For the kinetic studies, we use surface plasmon resonance in which one end
      of the DNA molecules is linked to a surface while the other end is free to
      interact with Ku. We find that one Ku molecule dissociates from 1-site DNA with
      simple Langmuir (i.e., independent) kinetics. However, two Ku molecules associate
      and dissociate from 2-site DNA with a time course that cannot be described as a
      simple Langmuir interaction. On 3- and 4-site DNA, EMSA and SPR studies do not
      reveal any cooperativity, suggesting that the middle Ku does not exhibit
      cooperative interaction with the two Ku molecules bound at the DNA ends. These
      results indicate that Ku molecules can demonstrate cooperative interaction, and
      this is influenced by their positions along the DNA.

PMID- 11583165
TI  - Rapid irreversible G protein alpha subunit misfolding due to intramolecular
      kinetic bottleneck that precedes Mg2+ "lock" after GTP/GDP exchange.
AB  - Stoichiometric exchange of GTP for GDP on heterotrimeric G protein alpha (Galpha)
      subunits is essential to most hormone and neurotransmitter initiated signal
      transduction. Galphas are stably activated in a Mg2+ complex with GTPgammaS, a
      nonhydrolyzable GTP analogue that is reported to bind Galpha, with very high
      affinity. Yet, it is common to find that substantial amounts (30-90%) of purified
      G proteins cannot be activated. Inactivatable G protein has heretofore been
      thought to have become "denatured" during formation of the obligatory nucleotide
      free or empty (MT) Galpha-state that is intermediary to GDP/GTP exchange at a
      single binding site. We find Galpha native secondary and tertiary structure to
      persist during formation of the irreversibly inactivatable state of transducin.
      MT Galpha is therefore irreversibly misfolded rather than denatured. Inactivation
      by misfolding is found to compete kinetically with protective but weak
      preequilibrium nucleotide binding at micromolar ambient GTPgammaS concentrations.
      Because of the weak preequilibrium, quantitative protection against Galpha
      aggregation is only achieved at free nucleotide concentrations 10-100 times
      higher than those commonly employed in G protein radio-nucleotide binding
      studies. Initial GTP protection is also poor because of the extreme slowness of
      an intramolecular Galpha refolding step (isomerization) necessary for GTP
      sequestration after its weak preequilibrium binding. Of the two slowly
      interconverting Galpha x GTP isomers described here, only the second can bind
      Mg2+, "locking" GTP in place with a large net rise in GTP binding affinity. A
      companion Galpha x GDP isomerization reaction is identified as the cause of the
      very slow spontaneous GDP dissociation that characterizes G protein nucleotide
      exchange and low spontaneous background activity in the absence of GPCR
      activation. Galpha x GDP and Galpha x GTP isomerization reactions are proposed as
      the dual target for GPCR catalysis of nucleotide exchange.

PMID- 11583166
TI  - Structural requirements of ceramide and sphingosine based inhibitors of
      mitochondrial ceramidase.
AB  - The effects of structural analogues of ceramide on rat brain mitochondrial
      ceramidase (mt-CDase) were investigated. Design of target compounds was mainly
      based on modifications of the key elements in ceramide and sphingosine, including
      stereochemistry, the primary and secondary hydroxyl groups, the trans double bond
      in the sphingosine backbone, and the amide bond. Mt-CDase was inhibited by (1)
      all stereoisomers of D-erythro-ceramide (D-e-Cer) with an IC50 of 0.11, 0.21, and
      0.26 mol % for the L-threo, D-threo, and L-erythro isomers, respectively; (2) all
      stereoisomers of sphingosine with IC50 ranging from 0.04 to 0.14 mol %, N-methyl
      D-erythro-sphingosine (N-Me-Sph, IC50 0.13 mol %); and (3) D-erythro-urea-C16
      ceramide (C16-urea-Cer IC50 0.33 mol %). The enzyme was not inhibited by N-methyl
      ceramide (N-Me-C16-Cer), 1-O-methyl ceramide (1-O-Me-C16-Cer), 3-O-methyl
      ceramide (3-O-Me-C16-Cer), cis-D-erythro ceramide (cis-D-e-C16-Cer) and 3-O
      methyl-D-erythro-sphingosine (3-O-Me-Sph). It was less potently inhibited by D
      erythro-sphinganine (D-e-dh-Sph, IC50 0.20 mol %), D-erythro-dehydro sphingosine
      (D-e-deh-Sph, IC50 0.25 mol %), (2S)-3-keto-sphinganine (3-keto-dh-Sph, IC50 0.34
      mol %), (2S) 3-keto-ceramide (3-keto-C16-Cer, IC50 0.60 mol %), and ceramine (C18
      ceramine, IC50 0.62 mol %), 1-O-methyl-D-erythro-sphingosine (1-O-Me-Sph), cis-D
      erythro-sphingosine (cis-D-e-Sph), (2S)-3-ketosphingosine (3-keto-Sph), (2S)-3
      keto-dehyrosphingosine (3-keto-deh-Sph), and N,N-dimethyl-D-erythrosphingosine
      (N,N-diMe-Sph) were weak inhibitors whereas ceramide-1-phosphate (Cer-1-P) and
      sphingosine-1-phosphate (Sph-1-P) stimulated the enzyme. Thus, for inhibition,
      the enzyme requires the primary and secondary hydroxyl groups, the C4-C5 double
      bond, the trans configuration of this double bond, and the NH-protons from either
      the amide of ceramide or the amine of sphingosine. Therefore, these results
      provide important information on the requirements for ceramide-enzyme
      interaction, and they suggest that ligand interaction with the enzyme occurs in a
      high affinity low specificity manner, in contrast to catalysis which is highly
      specific for D-erythro-ceramide (D-e-Cer) but occurs with a lower affinity. In
      addition, this study identifies two competitive inhibitors of mt-CDase; urea
      ceramide (C16-urea-Cer) and ceramine (C18-ceramine) that may be further developed
      and used to understand the mechanism of mt-CDase in vitro and in biologic
      responses.

PMID- 11583167
TI  - Calcium-dependent catalytic activity of a novel phytase from Bacillus
      amyloliquefaciens DS11.
AB  - The thermostable phytase from Bacillus amyloliquefaciens DS11 hydrolyzes phytate
      (myo-inositol hexakisphosphate, IP6) to less phosphorylated myo-inositol
      phosphates in the presence of Ca2+. In this report, we discuss the unique Ca2+
      dependent catalytic properties of the phytase and its specific substrate
      requirement. Initial rate kinetic studies of the phytase indicate that the enzyme
      activity follows a rapid equilibrium ordered mechanism in which binding of Ca2+
      to the active site is necessary for the essential activation of the enzyme. Ca2+
      turned out to be also required for the substrate because the phytase is only able
      to hydrolyze the calcium-phytate complex. In fact, both an excess amount of free
      Ca2+ and an excess of free phytate, which is not complexed with each other, can
      act as competitive inhibitors. The Ca2+-dependent catalytic activity of the
      enzyme was further confirmed, and the critical amino acid residues for the
      binding of Ca2+ and substrate were identified by site-specific mutagenesis
      studies. Isothermal titration calorimetry (ITC) was used to understand if the
      decreased enzymatic activity was related to poor Ca2+ binding. The pH dependence
      of the Vmax and Vmax/Km consistently supported these observations by
      demonstrating that the enzyme activity is dependent on the ionization of amino
      acid residues that are important for the binding of Ca2+ and the substrate. The
      Ca2+-dependent activation of enzyme and substrate was found to be different from
      other histidine acid phytases that hydrolyze metal-free phytate.

PMID- 11583168
TI  - Effect of nonbilayer lipids on membrane binding and insertion of the catalytic
      domain of leader peptidase.
AB  - Biological membranes contain a substantial amount of "nonbilayer lipids", which
      have a tendency to form nonlamellar phases. In this study the hypothesis was
      tested that the presence of nonbilayer lipids in a membrane, due to their overall
      small headgroup, results in a lower packing density in the headgroup region,
      which might facilitate the interfacial insertion of proteins. Using the catalytic
      domain of leader peptidase (delta2-75) from Escherichia coli as a model protein,
      we studied the lipid class dependence of its insertion and binding. In both lipid
      monolayers and vesicles, the membrane binding of (catalytically active) delta2-75
      was much higher for the nonbilayer lipid DOPE compared to the bilayer lipid DOPC.
      For the nonbilayer lipids DOG and MGDG a similar effect was observed as for DOPE,
      strongly suggesting that no specific interactions are involved but that the small
      headgroups create hydrophobic interfacial insertion sites. On the basis of the
      results of the monolayer experiments, calculations were performed to estimate the
      space between the lipid headgroups accessible to the protein. We estimate a
      maximal size of the insertion sites of 15 +/- 7 A2/lipid molecule for DOPE,
      relative to DOPC. The size of the insertion sites decreases with an increase in
      headgroup size. These results show that nonbilayer lipids stimulate the membrane
      insertion of delta2-75 and support the idea that such lipids create insertion
      sites by reducing the packing density at the membrane-water interface. It is
      suggested that PE in the bacterial membrane facilitates membrane insertion of the
      catalytic domain of leader peptidase, allowing the protein to reach the cleavage
      site in preproteins.

PMID- 11583169
TI  - Mutational analysis of the role of N-glycosylation in alpha-factor receptor
      function.
AB  - The alpha-factor mating pheromone receptor (encoded by STE2) activates a G
      protein signaling pathway that stimulates the conjugation of Saccharomyces
      cerevisiae yeast cells. The alpha-factor receptor is known to undergo several
      forms of post-translational modification, including phosphorylation, mono
      ubiquitination, and N-linked glycosylation. Since phosphorylation and mono
      ubiquitination have been shown previously to play key roles in regulating the
      signaling activity and membrane trafficking of the alpha-factor receptors, the
      role of N-linked glycosylation was investigated in this study. The Asn residues
      in the five consensus sites for N-linked glycosylation present in the
      extracellular regions of the receptor protein were mutated to prevent
      carbohydrate attachment at these sites. Mutation of two sites near the receptor N
      terminus (N25Q and N32Q) diminished the degree of receptor glycosylation, and the
      corresponding double mutant was not detectably N-glycosylated. The
      nonglycosylated receptors displayed normal function and subcellular localization,
      indicating that glycosylation is not important for wild-type receptor activity.
      However, mutation of the glycosylation sites resulted in improved plasma membrane
      localization for the Ste2-3 mutant receptors that are normally retained
      intracellularly at elevated temperatures. These results suggest that N
      glycosylation may be involved in the sorting process for misfolded Ste2 proteins,
      and may similarly affect certain mutant receptors whose altered trafficking is
      implicated in human diseases.

PMID- 11583170
TI  - Role of the K-channel in the pH-dependence of the reaction of cytochrome c
      oxidase with hydrogen peroxide.
AB  - The reaction of cytochrome c oxidase (COX) from Rhodobacter sphaeroides with
      hydrogen peroxide has been studied at alkaline (pH 8.5) and acidic (pH 6.5)
      conditions with the aid of a stopped-flow apparatus. Absorption changes in the
      entire 350-800 nm spectral range were monitored and analyzed by a global fitting
      procedure. The reaction can be described by the sequential formation of two
      intermediates analogous to compounds I and II of peroxidases: oxidized COX + H2O2
      --> intermediate I --> intermediate II. At pH as high as 8.5, intermediate I
      appears to be a mixture of at least two species characterized by absorption bands
      at approximately 607 nm (P607) and approximately 580 nm (F-I580) that rise
      synchronously. At acidic pH (6.5), intermediate I is represented mainly by a
      component with an alpha-peak around 575 nm (F-I575) that is probably equivalent
      to the so-called F* species observed with the bovine COX. The data are consistent
      with a pH-dependent reaction branching at the step of intermediate I formation.
      To get further insight into the mechanism of the pH-dependence, the peroxide
      reaction was studied using two mutants of the R. sphaeroides oxidase, K362M and
      D132N, that block, respectively, the proton-conducting K- and D-channels. The
      D132N mutation does not affect significantly the Ox --> intermediate I step of
      the peroxide reaction. In contrast, K362M replacement exerts a dramatic effect,
      eliminating the pH-dependence of intermediate I formation. The data obtained
      allow us to propose that formation of the acidic form of intermediate I (F-I575,
      F*) requires protonation of some group at/near the binuclear site that follows or
      is concerted with peroxide binding. The protonation involves specifically the K
      channel. Presumably, a proton vacancy can be generated in the site as a
      consequence of the proton-assisted heterolytic scission of the O-O bond of the
      bound peroxide. The results are consistent with a proposal [Vygodina, T. V.,
      Pecoraro, C., Mitchell, D., Gennis, R., and Konstantinov, A. A. (1998)
      Biochemistry 37, 3053-3061] that the K-channel may be involved in the delivery of
      the first four protons in the catalytic cycle (starting from reduction of the
      oxidized form) including proton uptake coupled to reduction of the binuclear site
      and transfer of protons driven by cleavage of the dioxygen O-O bond in the
      binculear site. Once peroxide intermediate I has been formed, generation of a
      strong oxene ligand at the heme a3 iron triggers a transition of the enzyme to
      the "peroxidase conformation" in which the K-channel is closed and the binuclear
      site becomes protonically disconnected from the bulk aqueous phase.

PMID- 11583171
TI  - Effect of hydrogen-bond networks in controlling reduction potentials in
      Desulfovibrio vulgaris (Hildenborough) cytochrome C3 probed by site-specific
      mutagenesis.
AB  - Cytochromes C3 isolated from Desulfovibrio spp. are periplasmic proteins that
      play a central role in energy transduction by coupling the transfer of electrons
      and protons from hydrogenase. Comparison between the oxidized and reduced
      structures of cytochrome C3 isolated from Desulfovibrio vulgaris (Hildenborough)
      show that the residue threonine 24, located in the vicinity of heme III,
      reorients between these two states [Messias, A. C., Kastrau, D. H. W., Costa, H.
      S., LeGall, J., Turner, D. L., Santos, H., and Xavier, A. V. (1998) J. Mol. Biol.
      281, 719-739]. Threonine 24 was replaced with valine by site-directed mutagenesis
      to elucidate its effect on the redox properties of the protein. The NMR spectra
      of the mutated protein are very similar to those of the wild type, showing that
      the general folding and heme core architecture are not affected by the mutation.
      However, thermodynamic analysis of the mutated cytochrome reveals a large
      alteration in the microscopic reduction potential of heme III (75 and 106 mV for
      the protonated forms of the fully reduced and oxidized states, respectively). The
      redox interactions involving this heme are also modified, while the remaining
      heme-heme interactions and the redox-Bohr interactions are less strongly
      affected. Hence, the order of oxidation of the hemes in the mutated cytochrome is
      different from that in the wild type, and it has a higher overall affinity for
      electrons. This is consistent with the replacement of threonine 24 by valine
      preventing the formation of a network of hydrogen bonds, which stabilizes the
      oxidized state. The mutated protein is unable to perform a concerted two-electron
      step between the intermediate oxidation stages, 1 and 3, which can occur in the
      wild-type protein. Thus, replacing a single residue unbalances the global network
      of cooperativities tuned to control thermodynamically the directionality of the
      stepwise electron transfer and may affect the functionality of the protein.

PMID- 11583172
TI  - Steady-state kinetics of substrate binding and iron release in tomato ACC
      oxidase.
AB  - 1-Aminocyclopropane-1-carboxylate oxidase (ACC oxidase) catalyzes the last step
      in the biosynthetic pathway of the plant hormone, ethylene. This unusual reaction
      results in the oxidative ring cleavage of 1-aminocyclopropane carboxylate (ACC)
      into ethylene, cyanide, and CO2 and requires ferrous ion, ascorbate, and
      molecular oxygen for catalysis. A new purification procedure and assay method
      have been developed for tomato ACC oxidase that result in greatly increased
      enzymatic activity. This method allowed us to determine the rate of iron release
      from the enzyme and the effect of the activator, CO2, on this rate. Initial
      velocity studies support an ordered kinetic mechanism where ACC binds first
      followed by O2; ascorbate can bind after O2 or possibly before ACC. This kinetic
      mechanism differs from one recently proposed for the ACC oxidase from avocado.

PMID- 11583174
TI  - NMR-detected order in core residues of denatured bovine pancreatic trypsin
      inhibitor.
AB  - The NMR characteristics of [14-38]Abu, a synthetic variant of BPTI that is
      partially folded in aqueous buffer near neutral pH, support a model of early
      folding events which begin with stabilization of the nativelike, slow exchange
      core [Barbar, E., Hare, M., Daragan, V., Barany, G., and Woodward, C. (1998)
      Biochemistry 37, 7822-7833 (1)]. In partially folded [14-38]Abu, urea
      denaturation profiles for representative amide protons show that global unfolding
      is non-two-state and that core residues require a higher concentration of urea to
      unfold. Dynamic properties of pH-denatured [14-38]Abu and fully reduced and
      unfolded BPTI analogue were determined from heteronuclear NMR relaxation
      measurements at similar solution conditions. Differences at various sites in the
      polypeptide chain were evaluated from spectral density functions determined from
      T1, T2, and steady-state heteronuclear NOE data. Although denatured [14-38]Abu
      contains no persistent secondary structure, its most ordered residues are those
      that, in native BPTI, fold into the slow exchange core. The fully reduced
      analogue is significantly more mobile and shows less heterogeneous dynamics, but
      at 1 degree C, restricted motion is observed for residues in the central segments
      of the polypeptide chain. These observations indicate that there is a developing
      core or cores even in highly unfolded species. Apparently the effect of 14-38
      disulfide on unfolded

PMID- 11583173
TI  - Strain-based sequence variations and structure analysis of murine prostate
      specific spermine binding protein using mass spectrometry.
AB  - Mouse spermine binding protein (SBP) has been characterized using mass
      spectrometry, including its localization within the prostate, sequence
      verification, and its posttranslational modifications. MALDI (matrix-assisted
      laser desorption/ionization) mass spectrometry was employed for localization of
      proteins expressed by different lobes of the mouse prostate obtained after tissue
      blotting on a polyethylene membrane. The mass spectra showed complex protein
      profiles that were different for each lobe of the prostate. The prostate-specific
      spermine binding protein (SBP), primarily identified by its in-source decay
      fragment ion signals, was found predominantly expressed by the ventral lobe of
      the prostate. The MALDI in-source decay measurements combined with nanoESI
      (nanoelectrospay ionization) MS/MS measurements obtained after specific
      proteolysis of SBP, allowed the exact positioning of a single N-linked
      carbohydrate group, and the identification of a pyroglutamate residue at the
      sequence N-terminus. The N-linked carbohydrate component was further investigated
      and the general pattern of the N-linked carbohydrate identified. The presence of
      a disulfide bridge between cysteine78 and cysteine124 was also established. The
      full sequence characterization of SBP showed several strain-based sequence
      differences when compared to the published gene sequence.

PMID- 11583175
TI  - A catalytic diad involved in substrate-assisted catalysis: NMR study of hydrogen
      bonding and dynamics at the active site of phosphatidylinositol-specific
      phospholipase C.
AB  - Phosphatidylinositol-specific phospholipase Cs (PI-PLCs, EC 3.1.4.10) are
      ubiquitous enzymes that cleave phosphatidylinositol or phosphorylated
      derivatives, generating second messengers in eukaryotic cells. A catalytic diad
      at the active site of Bacillus cereus PI-PLC composed of aspartate-274 and
      histidine-32 was postulated from the crystal structure to form a catalytic triad
      with the 2-OH group of the substrate [Heinz, D. W., et al. (1995) EMBO J. 14,
      3855-3863]. This catalytic diad has been observed directly by proton NMR. The
      single low-field line in the 1H NMR spectrum is assigned by site-directed
      mutagenesis: The peak is present in the wild type but absent in the mutants H32A
      and D274A, and arises from the histidine Hdelta1 forming the Asp274-His32
      hydrogen bond. This hydrogen is solvent-accessible, and exchanges slowly with H2O
      on the NMR time scale. The position of the low-field peak shifts from 16.3 to
      13.8 ppm as the pH is varied from 4 to 9, reflecting a pKa of 8.0 at 6 degrees C,
      which is identified with the pKa of His32. The Hdelta1 signal is modulated by
      rapid exchange of the Hepsilon2 with the solvent. Estimates of the exchange rate
      as a function of pH and protection factors are derived from a line shape
      analysis. The NMR behavior is remarkably similar to that of the serine proteases.
      The postulated function of the Asp274-His32 diad is to hydrogen-bond with the 2
      OH of phosphatidylinositol (PI) substrate to form a catalytic triad analogous to
      Asp-His-Ser of serine proteases. This is an example of substrate-assisted
      catalysis where the substrate provides the catalytic nucleophile of the triad.
      This hydrogen bond becomes shorter as the imidazole is protonated, suggesting it
      is stronger in the transition state, contributing further to the catalytic
      efficiency. The hydrogen bond fits the NMR criteria for a short, strong hydrogen
      bond, i.e., a highly deshielded proton resonance, bond length of 2.64 +/- 0.04 A
      at pH 6 measured by NMR, a D/H fractionation factor significantly lower than 1.0,
      and a protection factor > or = 100.

PMID- 11583177
TI  - ESMO minimum clinical recommendations--the beginning of a process.

PMID- 11583176
TI  - Are european cancer patients getting a fair deal?

PMID- 11583178
TI  - Chemoradiotherapy for rectal cancer--is there an optimal combination?
AB  - PURPOSE: Chemoradiotherapy is increasingly used in the primary management of
      rectal cancer. A critical review of present knowledge of whether an optimal
      combination exists was made for each of the major clinical situations. RESULTS:
      As preoperative therapy to reduce local recurrence rates in primarily resectable
      rectal cancers, radiotherapy has almost exclusively been used as single modality,
      and combined chemoradiotherapy should remain experimental until further evidence
      is available. This can only be achieved in randomised trials. Postoperatively, a
      combination of chemotherapy and radiotherapy appears to be more efficient in
      reducing local failure rates and improving survival than either modality alone,
      but the literature-based evidence is partly conflicting. As a reference
      treatment, a combination of continuous infusion 5-fluorouracil (5-FU) and
      radiotherapy can be advocated based upon one trial. In primarily irresectable
      cancer, there is some support that chemoradiotherapy may be more efficient than
      radiotherapy alone in causing tumour regression allowing radical surgery, but the
      literature is again conflicting. A great number of phase II studies have been
      performed in these cancers and in those considered to be locally advanced,
      revealing promising activity and claims of superiority to radiotherapy alone or
      other schedules. The studies are, however, inconclusive with respect to
      antitumour activity, and patient selection may be of greater relevance for the
      results. Chemoradiation has also increasingly been used to facilitate a sphincter
      preserving procedure in low-lying cancers. Again, literature is inconclusive as
      to whether an optimal combination exists, whether it is superior to radiotherapy
      alone, or if it actually facilitates sphincter preservation at all. Long-term
      functional outcome is poorly known. Again, 5-FU has been most extensively used,
      but many other drugs are presently being tested in various combinations.
      CONCLUSIONS: An optimal combination of chemoradiotherapy for rectal cancer does
      not exist. Actually, a critical review of the literature shows that the support
      for superiority of chemoradiation over radiation alone is weak, or lacking. There
      is a great need of both more conclusive study designs and a more rational
      exploration of drug-radiation interactions prior to clinical testing.

PMID- 11583179
TI  - ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and
      follow-up of primary breast cancer.

PMID- 11583180
TI  - ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of
      non-small-cell lung cancer (NSCLC).

PMID- 11583181
TI  - ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of
      small-cell lung cancer (SCLC).

PMID- 11583182
TI  - ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and
      follow-up of colon cancer.

PMID- 11583183
TI  - ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of
      advanced colorectal cancer.

PMID- 11583184
TI  - ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of
      cancers of unknown primary site (CUP).

PMID- 11583185
TI  - ESMO Recommendations for prophylaxis of chemotherapy-induced nausea and vomiting
      (NV).

PMID- 11583186
TI  - Combination chemotherapy with docetaxel plus vinorelbine in metastatic breast
      cancer patients with prior exposure to anthracyclines.
AB  - PURPOSE: To evaluate the anti-tumor activity and tolerance of docetaxel plus
      vinorelbine in metastatic breast cancer (MBC) patients previously treated with
      anthracyclines. PATIENTS AND METHODS: Fifty patients with MBC were treated with
      docetaxel 75 mg/m2 (subsequently reduced to 60 mg/m2) plus vinorelbine 30 mg/m2
      (subsequently reduced to 24 mg/m2). both on day 1, every 3 weeks, for a maximum
      of six cycles. All patients had previously received anthracyclines as adjuvant
      treatment (< 12 months disease-free interval) or first-line therapy for MBC.
      Thirty-seven patients had received at least one prior regimen for MBC. Twenty
      five patients had prior high-dose chemotherapy with stem-cell rescue. Thirty
      patients had multiple metastatic sites. Liver and lung disease were the
      predominant metastatic site in 31 patients. RESULTS: Forty-nine patients were
      assessable for response. Nineteen patients achieved a partial response and four a
      complete response (overall response rate, 46%; 95% confidence interval (95% CI):
      32%-60%). Fourteen patients (28%) had stable disease on treatment. Median Kaplan
      Meier estimated progression-free and duration of response times are 21 and 29
      weeks. Median survival time is 47 weeks. Hematological dose-limiting toxicity,
      prompted a 20% dose reduction for both drugs after the first thirteen patients
      were treated. Neutropenia > or = grade 3 occurred in nineteen (34%) patients,
      neutropenic fever in 15 (7) courses, and mucositis > or = grade 3 in 6 (3%)
      courses. CONCLUSIONS: The combination of docetaxel plus vinorelbine on day 1
      every 3 weeks is feasible and active in MBC patients with prior anthracycline
      exposure. This regimen is safe, well-tolerated and convenient for the patients.

PMID- 11583187
TI  - Cardiac function following combination therapy with paclitaxel and doxorubicin:
      an analysis of 657 women with advanced breast cancer.
AB  - BACKGROUND: To determine the cardiotoxicity of paclitaxel (T) plus doxorubicin
      (A) combination therapy in women with advanced breast cancer. To define a dose
      range of A for use in AT. PATIENTS AND METHODS: The effect of cumulative A dose
      on risk of congestive heart failure (CHF) and alterations of myocardial
      contractility (left ventricular ejection fraction [LVEF] decrease > or = 20% or
      to <50%) was estimated from pooled data from 10 trials of AT. RESULTS: Thirty-one
      of 657 patients (4.7%) developed CHF at a median of 6.6 months (range 0.3-24.6)
      after initiation of AT. CHF was stabilized in 29 patients at a median of 17.3
      months after diagnosis (range 4.1-31.2 months). The risk of developing CHF was <
      or = 5% at a total A dose < or = 380 mg/m2. In patients who received a total A
      dose > 440 mg/m2, the incidence of CHF was >25% but similar to that of A
      monotherapy. The risk of CHF was similar in women receiving AT or A monotherapy
      at a dose < or = 380 mg/m2 (2%-3%). LVEF progressively decreased in patients who
      received AT, especially at a cumulative A dose > 380 mg/m2. LVEF decreases were
      more frequent in patients who later developed CHF, but the majority of CHF
      patients did not experience LVEF alterations prior to symptoms. LVEF recovered
      after discontinuation of A in 25 of 67 women who developed LVEF < 50%.
      CONCLUSION: The reported cardiac effects are consistent with anthracycline
      related cardiotoxicity. AT is associated with a cardiac risk similar to that of A
      monotherapy up to a cumulative A dose of 340-380 mg/m2.

PMID- 11583188
TI  - Targeted intra-operative radiotherapy (Targit): an innovative method of treatment
      for early breast cancer.
AB  - INTRODUCTION: We believe that conservative treatment of early breast cancer may
      not require radiotherapy that encompasses the whole breast. We present here the
      clinico-pathological basis for this view, as well as a novel therapeutic approach
      that allows intra-operative radiotherapy to be safely and accurately delivered to
      the target tissues in a standard operating theatre. THE RATIONALE: Whole-organ
      analysis of mastectomy specimens reveals that 80% of occult cancer foci are
      situated remote from the index quadrant. In contrast, over 90% of local
      recurrences after breast conservative therapy occur near the original tumour,
      even when radiotherapy is not given. Therefore, the remote occult cancer foci may
      be clinically irrelevant and radiotherapy to the index quadrant alone might be
      sufficient. A NOVEL TECHNIQUE: The Photon Radiosurgery System (PRS) is an
      ingenious portable electron-beam driven device that can typically deliver intra
      operative doses of 5-20 Gy, respectively, to 1 cm and 0.2 cm from the tumour bed
      over about 22 min. The pliable breast tissue--the target--wraps around the
      source, providing perfect conformal radiotherapy. Being soft X-rays, the dose
      attenuates rapidly (alpha approximately 1/r3), reducing distant damage. RESULTS:
      In our pilot study of 25 patients (age 30-80 years, T = 0.42-4.0 cm), we replaced
      the routine post-operative tumour bed boost with targeted intra-operative
      radiotherapy. There have been no major complications and no patient has developed
      local recurrence, although the median follow-up time is short, at 24 months.
      CONCLUSION: It is safe and feasible to deliver targeted intraoperative
      radiotherapy (Targit) for early breast cancer. We have begun a randomised trial-
      the first of its kind--comparing Targit with conventional six-week course of
      radiotherapy. If proven equivalent in terms of local recurrence and cosmesis, it
      could eliminate the need for the usual six-week course of post-operative
      radiotherapy.

PMID- 11583189
TI  - HER-2 and topo-isomerase IIalpha as predictive markers in a population of node
      positive breast cancer patients randomly treated with adjuvant CMF or epirubicin
      plus cyclophosphamide.
AB  - BACKGROUND: The predictive role of HER-2 in node-positive breast cancer patients
      receiving CMF or an anthracycline-based adjuvant therapy remains unclear. In
      addition, topo-isomerase II alpha (topo IIalpha), as the cellular target of
      anthracyclines, might have value as a predictive marker. PATIENTS AND METHODS:
      Four hundred eighty-one archival primary tumor samples were collected among 777
      patients entered into a multicenter phase III trial comparing classical CMF with
      epirubicin cyclophosphamide (HEC) as adjuvant therapy of node-positive breast
      cancer. HER-2 was evaluated by immunohistochemistry (IHC) using different
      antibodies (Abs). Topo IIalpha was evaluated by IHC using the Ab KiS 1. In each
      subgroup of patients identified by HER-2 and topo IIalpha, adjusted hazard ratios
      for event-free survival (EFS) and the corresponding 95% confidence intervals have
      been calculated for the different study comparisons. An interaction test has been
      performed to investigate the role of HER-2 and topo IIalpha as predictive
      markers. RESULTS: When HER-2 was evaluated by CB-11 and 4D5 mAbs, the EFS
      adjusted hazard ratios (HR) for the main study comparison HEC vs. CMF were: HER-2
      positive: 0.33 (95% confidence interval (95% CI): 0.09 1.27, P = 0.08), HER-2
      negative: 1.16 (95%, CI: 0.71-1.90, P = 0.56); the P-value for the interaction
      test was 0.10. When HER-2 was evaluated by TAB-250 + pAbl Abs, the adjusted HR
      for the same comparison were: HER-2 positive: 1.06 (95% CI: 0.45-2.52, P = 0.90),
      HER-2 negative: 0.99 (95% CI: 0.58-1.68, P = 0.97); the P-value for the
      interaction test was 0.84. With regard to topo IIalpha, the adjusted HR for the
      EFS comparison HEC vs. CMF were: topo IIalpha positive: 0.66 (95% CI: 0.32-1.36,
      P = 0.25), topo IIalpha negative: 1.26 (95% CI: 0.63-2.50, P = 0.51); the P-value
      for the interaction test was 0.13. CONCLUSIONS: This study suggests that in node
      positive breast cancer patients randomly treated with CMF or an epirubicin-based
      regimen, the predictive value of HER-2 may vary according to the Abs used in the
      immunohistochemistry assay. In addition, the study supports the concept that topo
      IIalpha might be involved in the determination of tumor responsiveness to an
      anthracycline-based adjuvant therapy.

PMID- 11583190
TI  - Ipsilateral supraclavicular lymph nodes metastases from breast cancer as only
      site of disseminated disease. Chemotherapy alone vs. induction chemotherapy to
      radical radiation therapy.
AB  - BACKGROUND: To define the role of radiotherapy (RT) in the treatment of
      ipsilateral supraclavicular lymph-nodes metastases (ISLM) from breast cancer as
      only site of disseminated disease, we started a prospective non-randomized
      clinical trial in 1989. Here we report the final results with a median follow-up
      of 8.75 years. PATIENTS AND METHODS: Thirty-seven patients (pts), with ISLM from
      breast cancer, were consecutively enrolled into two arms. Arm A (18 pts):
      chemotherapy (CT) for six courses. Arm B (19 pts): CT for three courses followed
      by RT to the site of ISLM at 'radical' dose of 50-60 Gy. RESULTS: In arm A, a
      median Time to Progression (TtP) of 7 months with a median Overall Survival (OS)
      of 28 months was recorded. In comparison, patients in arm B had a longer median
      TtP with 20 months as well as a better median OS with 41 months, respectively. An
      actuarial five-year disease-free survival of 5.5% was obtained in arm A vs. 21%
      in arm B. A statistically significant difference in TtP was demonstrated between
      the two groups (P = 0.01). CONCLUSIONS: These data demonstrate that a better
      event-free survival could be achieved in patients with ISLM submitted to
      induction CT and radical irradiation. This also translated into a longer survival
      although this did not achieve statistical significance. We want to stress the
      importance of local control by RT since it does imply that not all of these
      patients have micrometastases at the time of relapse in the supraclavicular
      fossa.

PMID- 11583191
TI  - Identification of the highest dose of docetaxel associable with active doses of
      epirubicin. Results from a dose-finding study in advanced breast cancer patients.
AB  - PURPOSE: To determine the maximum tolerated dose (MTD) and the dose limiting
      toxicity (DLT) of docetaxel in combination with fixed doses of epirubicin.
      PATIENTS AND METHODS: Women with locally advanced or metastatic breast cancer
      were given docetaxel, 60 mg/m2 in escalated doses by steps of 10 mg/m2, in
      association with two fixed doses of epirubicin (90 mg/m2, and 75 mg/m2). Since
      neutropenia was foreseen to be the most likely DLT, a third group with
      prophylactic G-CSF support was planned to define the MTD of docetaxel with 90
      mg/m2 of epirubicin. Selected patients underwent pharmacokinetic evaluation of
      docetaxel. RESULTS: Fifty-eight patients entered the study. At the first step (90
      mg/m2 of epirubicin) the MTD was obtained at 60 mg/m2 of docetaxel. At the second
      step (75 mg/m2 of epirubicin) the MTD of docetaxel was 80 mg/m2. At the third
      step (epirubicin 90 mg/m2) G-CSF allowed a safe escalation of docetaxel up to 90
      mg/m2. Neutropenia was the most common hematological adverse event. Without G
      CSF, grade 4 neutropenia occurred in 69% of cycles, of which 11% was complicated
      by fever. In G-CSF group, grade 4 neutropenia and neutropenic fever occurred in
      31% and 3%, respectively. Most frequent non-hematological adverse effects were
      asthenia (45%), nausea (39%) and mucositis (36%). No patient developed congestive
      heart failure. Two toxic deaths occurred. Overall response rate was 73% in 42 out
      of 58 patients, with no apparent epirubicin dose-related effect. No statistically
      significant effect of the two doses of epirubicin was observed in docetaxel
      pharmacokinetics. CONCLUSIONS: On the basis of the toxicity profile, the
      docetaxel pharmacokinetics and the response rate observed, epirubicin 75 mg/m2
      combined with docetaxel 80 mg/m2 can be recommended for further studies.

PMID- 11583192
TI  - Routine follow-up examinations in breast cancer patients have minimal impact on
      life expectancy: a simulation study.
AB  - BACKGROUND: Little is known about the effects of routine follow-up examinations
      on life expectancy in cancer patients. Lately, the benefits of follow-up
      examinations have been debated, which has given rise to less extensive, though
      still frequent, follow-up strategies. In this study, a simulation model was
      applied to evaluate the impact of different follow-up strategies on life
      expectancy in breast cancer patients. MATERIALS AND METHODS: A five-state Markov
      chain model was developed, with which various follow-up strategies with regard to
      frequency and elaborateness were simulated. Calculations were based on a
      hypothetical population of breast cancer patients treated with curative intent.
      Medical aspects were studied, such as life expectancy and the proportion of
      patients who died from breast cancer. Social and psychological aspects and
      quality of life were not taken into account. Data from the literature were used
      to estimate the parameters needed for the model. RESULTS: The gain in life
      expectancy with standard follow-up compared to no follow-up examination, was
      about 2 months in breast cancer patients aged 50 years treated with curative
      intent. The percentage of patients who died from breast cancer was 45.4% with
      standard follow-up, versus 45.8% without follow-up. In older women, the gain was
      even less. Sensitivity analyses showed that the effects on life expectancy were
      robust. CONCLUSIONS: Our model showed that standard follow-up had minimal impact
      on the prognosis of breast cancer patients. It may be unnecessary to continue
      standard follow-up by medical specialists after the end of the surveillance
      period of the primary therapy, provided that the patients continue to have easy
      access to health care facilities in the case of symptoms or concern. However,
      future research is needed to study quality of life aspects of follow-up.

PMID- 11583193
TI  - Second-line carboplatin and gemcitabine in platinum sensitive ovarian cancer--a
      dose-finding study by the Arbeitsgemeinschaft Gynakologische Onkologie (AGO)
      Ovarian Cancer Study Group.
AB  - BACKGROUND: Despite the progress that has been achieved in the last years,
      recurrence rates in ovarian cancer patients are still considerably high and the
      majority of patients ultimately become candidates for second-line treatment.
      Carboplatin reinduction is a broadly adopted regimen in patients with recurrences
      occurring six months or later after first-line treatment. Gemcitabine is among
      the candidates as combination partner in second-line regimens. PATIENTS AND
      METHODS: We performed a study with escalating doses of gemcitabine combined with
      carboplatin in 26 platinum-pretreated patients with recurrent ovarian cancer and
      a treatment-free interval of 6+ months. Dose-limiting toxicity (DLT) and a
      maximum tolerable dose (MTD) recommendable for further trials was evaluated.
      RESULTS: The DLT was myelosuppression, mainly thrombocytopenia. No dose limiting
      non-hematological toxicities were observed. The MTD of gemcitabine was 1,000
      mg/m2 given on days 1 + 8 of a three-week schedule combined with carboplatin AUC
      4 given on day 1. The majority of evaluable patients showed an objective response
      (62.5%), and median progression-free and overall survival were 10 and 18+ months,
      respectively. CONCLUSION: Gemcitabine-carboplatin given according to the MTD is
      well tolerated and active against recurrent platinum-sensitive disease. A
      randomized trial comparing carboplatin with or without gemcitabine in platinum
      sensitive ovarian cancer has already been initiated.

PMID- 11583194
TI  - Expression of nucleolar protein p120 predicts poor prognosis in patients with
      stage I lung adenocarcinoma.
AB  - BACKGROUND: P120 is a proliferation-associated nucleolar protein found in most
      human malignant tumors, but not in resting normal cells. In our previous studies,
      the expression of p120 was statistically correlated with the proliferation
      capacity in human lung cancer cells and could be a prognostic marker for resected
      lung adenocarcinoma. PATIENTS AND METHODS: The expression levels of p120 in
      tumors were assessed by immunohistochemistry in 59 patients with stage I lung
      adenocarcinoma who underwent radical resection. Using clinical follow-up data,
      the prognostic significance of p120 calculated by labeling indices was evaluated
      using Cox's proportional hazard model. RESULTS: A mean +/- SD of the labeling
      index of p120 was 35.3+/-14.4%. No significant correlation was found between the
      expression levels of p120 and clinicopathological factors. Using a cutoff value
      of 35% in the labeling index of p120, patients with high expression of p120
      experienced early recurrence and shorter survival compared with those having low
      expression of p120 (P = 0.04). Multivariate analysis revealed that p120 served as
      an independent and strongest prognostic factor for resected lung adenocarcinoma
      (P = 0.033). CONCLUSION: This article provides the first evidence that the
      expression levels of p120 in tumor tissues can be used as an independent and
      powerful prognostic marker for resected stage I lung adenocarcinoma.

PMID- 11583195
TI  - Correlation between c-erbB-4 receptor expression and response to gemcitabine
      cisplatin chemotherapy in non-small-cell lung cancer.
AB  - BACKGROUND: While the overexpression of c-erbB gene family in several
      malignancies is associated with poorer prognosis, the association between the
      expression of the cellular markers and the response to chemotherapy is not yet
      clear. In this study we investigated the expression of c-erbB-4 receptor in NSCLC
      and correlated it with the response to gemcitabine-cisplatin combination
      chemotherapy. PATIENTS AND METHODS: Forty-three NSCLC patients with
      histologically or cytologically proven disease were treated with gemcitabine
      cisplatin combination chemotherapy. Immunohistochemical stains for c-erbB-4
      receptor were performed in 20 cases on paraffin sections using the avidin-biotin
      peroxidase method. RESULTS: Two patients achieved complete response (5%), and 16
      achieved partial response (37%) yielding an overall objective response rate of
      42%. Minimal response was observed in seven patients (16%) and disease
      stabilization in 7%. Immunohistochemical stain was positive for the presence of c
      erbB-4 receptor in 25% of patients, and negative in 75%. No response was
      documented in c-erbB-4 positive patients (0 of 5) while an objective response
      (complete, partial or minimal) was seen in 11 of 15 (73%) c-erbB-4 negative
      patients. Negative stain for c-erbB-4 significantly favored response to
      gemcitabine-cisplatin combination (P < 0.01). CONCLUSION: C-erbB-4 expression
      status showed no correlation with survival and cannot be accepted at this time as
      a guiding factor for therapeutic management. These interesting results deserve
      further evaluation in a large-scale prospective trial before treatment
      recommendations on the basis of c-erbB-4 presence can be finally made.

PMID- 11583196
TI  - Phase II trial of paclitaxel by three-hour infusion for advanced gastric cancer
      with short premedication for prophylaxis against paclitaxel-associated
      hypersensitivity reactions.
AB  - PURPOSE: To determine the antitumor activity and toxicity of paclitaxel
      administered as a three-hour infusion and to estimate the incidence of
      hypersensitivity reactions using a short-course prophylaxis regimen in patients
      with advanced gastric cancer. PATIENTS AND METHODS: Sixty patients with advanced
      measurable gastric cancer and performance status 0 to 2, who had received at most
      one prior chemotherapy regimen, were treated with paclitaxel 210 mg/m2 over three
      hours following a short-course premedication with dexamethasone, diphenhydramine
      and ranitidine administered 30 min prior to the delivery of paclitaxel. Cycles
      were repeated every three weeks. Twenty-six patients (43%) had received prior
      chemotherapy for metastatic disease and six patients had received adjuvant
      chemotherapy. The response rate to prior chemotherapy was 50% (13 of 26).
      RESULTS: Objective responses were observed in 14 of 60 patients (23%; 95%
      confidence interval (95% CI): 13%-36%). Six of twenty-eight (21%) patients with
      no prior chemotherapy and 7 of 26 (27%) previously treated patients for
      metastatic disease developed a PR. There were no complete responses. The median
      duration of response was 152 days. The study treatment was well tolerated. Twenty
      two of sixty patients (37%) experienced grade 3 or 4 neutropenia, which was the
      most common and serious toxicity. Grade 3 peripheral neuropathy occurred in one
      patient. Hypersensitivity reactions were observed in only nine patients (15%) and
      were all grade 1. CONCLUSIONS: A three-hour infusion of paclitaxel is both an
      active and safe treatment for gastric cancer using the short-course premedication
      schedule. Paclitaxel appears to be non-cross resistant to other active agents for
      gastric cancer.

PMID- 11583197
TI  - Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma.
      Study of the Eastern Cooperative Oncology Group-E6282.
AB  - BACKGROUND: A phase II study of dacarbazine (DTIC), was conducted to determine
      the response rate, duration of response, toxicity and overall survival of
      patients with advanced pancreatic islet cell tumors. PATIENTS AND METHODS: Fifty
      patients with advanced pancreatic islet cell tumors, having progressive symptoms
      or evidence of rapidly advancing disease were entered on this study. DTIC was
      given by IV infusion at a dose of 850 mg/m2, over 60-90 minutes, repeated every
      four weeks. RESULTS: The response rate was 33% in 42 patients who had measurable
      tumor, and 34% in the 50 patients (90% confidence interval (90% CI): 23%-47%).
      The majority of the responses were seen in patients without prior chemotherapy.
      Median overall survival was 19.3 months. There were two lethal toxicities on the
      study, one septic shock and one myocardial infarction. Grade 4 toxicities were,
      hematological (5 patients), sepsis, neurological (depression and paranoid
      behavior) and bleeding (1 patient each). The most common toxicity was vomiting,
      grade 3 in 13% of patients. CONCLUSIONS: DTIC has activity in advanced previously
      untreated pancreatic islet cell tumors.

PMID- 11583198
TI  - Predictive factors of disease-free survival for non-metastatic osteosarcoma of
      the extremity: an analysis of 300 patients treated at the Rizzoli Institute.
AB  - BACKGROUND: To identify predictive factors of disease-free survival (DFS) in
      patients with non-metastatic osteosarcoma of the extremity, treated with primary
      chemotherapy and delayed surgery. PATIENTS AND METHODS: The relationship between
      patient-related and treatment-related factors and prognosis was evaluated in 300
      patients treated from 1986 to 1992 according to chemotherapy protocols based on
      high-dose methotrexate, cisplatin and doxorubicin, with the addition of
      ifosfamide in the post-operative phase. Univariate and multivariate analyses of
      prognostic factors for disease-free survival were performed. RESULTS: With a
      median follow-up of 9.2 (4.4-12) years, eight-year DFS was 59% (95% confidence
      interval (95% CI): 54-64.9). Univariate analyses showed that tumor volume > or =
      150 ml (P = 0.002), histologic subtype (P = 0.028), age > 12 years (P = 0.044),
      high serum lactate dehydrogenase (P = 0.044) and alkaline phosphatase (P = 0.064)
      levels adversely affected DFS. Gender of patients and site of tumor did not
      influence DFS. No differences in DFS were found among the three chemotherapy
      protocols, whereas the use of limb-sparing surgery vs. amputation or rotation
      plasty (P = 0.006) and a good histologic response to primary chemotherapy (P =
      0.014) positively correlated with DFS. After multivariate analyses, tumor volume
      > or = 150 ml (P = 0.028), age > 12 years (P = 0.051), and histologic subtype (P
      = 0.052) retained prognostic significance. CONCLUSIONS: In patients with non
      metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy,
      the disease-free survival is significantly influenced by tumor volume, age, and
      histologic subtype.

PMID- 11583199
TI  - Assessment of amifostine as protection from chemotherapy-induced toxicities after
      conventional-dose and high-dose chemotherapy in patients with germ cell tumor.
AB  - BACKGROUND: We assessed the efficacy of amifostine for protection from
      chemotherapy-induced toxicities in patients treated with conventional-dose
      paclitaxel, ifosfamide, cisplatin (TIP) and high-dose carboplatin, etoposide and
      thiotepa (CET) followed by peripheral blood progenitor cell (PBPC) rescue.
      PATIENTS AND METHODS: In a prospective single-center study 40 patients with
      relapsed or refractory germ-cell tumors (GCT) were treated with 3 cycles of
      conventional-dose TIP followed by one cycle of high-dose CET. Patients were
      randomized either to receive one fixed dose of 500 mg amifostine per day of
      conventional-dose TIP and two fixed doses of 500 mg per day amifostine during
      high-dose CET (group A, n = 20) or no amifostine (group B, n = 20). Prior to the
      first cycle of TIP, one course of 175 mg/m2 paclitaxel and 5 g/m2 ifosfamide (TI)
      followed by granulocyte-colony stimulating factor (G-CSF) at 10 microg/kg/day
      were given for PBPC mobilization. RESULTS: Toxicities and response to
      conventional-dose TIP and high-dose CET could be evaluated in 40 patients (100%)
      and 32 of 40 patients (80%), respectively. Peripheral neurotoxicity (i.e.
      paresthesia or sensorymotor impairment), hearing impairment, hematologic
      toxicity, nephrotoxicity, nausea, myalgia, skin- and liver-toxicity did not
      differ siginificantly between the two patient groups. Likewise, the response
      rates to TIP and high-dose CET were comparable in patients with or without
      amifostine. After a median follow-up of 18 months, 8 of 20 (40%) patients of
      group A and 6 of 20 (30%) patients of group B are without relapse. CONCLUSION:
      Repeated low doses of 500 mg amifostine additional to conventional-dose TIP or
      high-dose CET showed no unequivocal advantage in protection from treatment
      related toxicities. Furthermore, no significant differences in response rates or
      survival could be observed in this small number of patients.

PMID- 11583200
TI  - Undifferentiated nasopharyngeal carcinoma in children and adolescents: comparison
      between staging systems.
AB  - BACKGROUND: New criteria for classifying nasopharyngeal carcinoma were defined in
      the 5th edition of the American Joint Committee on Cancer (AJCC) staging manual.
      We investigated the clinical implications of the new system by comparing it with
      the 4th edition in a cohort of pediatric undifferentiated nasopharyngeal
      carcinoma (UNPC). PATIENTS AND METHODS: We retrospectively restaged 54 patients
      younger than 17 years who had biopsy-proven UNPC, treated between 1965 and 1999
      in a single institution. RESULTS: Using the 5th edition an overall downstaging of
      the population according to T status, N status, and stage grouping was evident
      along with a better correlation with likelihood of survival. The comparison
      between local and advanced disease according to T stage (T1+T2 vs. T3+T4) became
      highly significant in the new system (P = 0.0011 vs. P = 0.067 in the 4th
      edition). CONCLUSIONS: As far as prognostic categories are concerned, the 5th
      edition of the AJCC staging manual appears to be an improvement over the previous
      classification, even though for pediatric patients a uniform distribution among
      stages cannot be observed because most children present with advanced disease.
      The overall downstaging should be taken into consideration for the stratification
      of patients in future trials.

PMID- 11583201
TI  - Childhood leiomyosarcoma: a report from the soft tissue sarcoma Italian
      Cooperative Group.
AB  - BACKGROUND: Only a few reports on the clinical features and management of
      childhood leiomyosarcoma are available. To contribute additional information on
      the management of this rare tumor, we report on a series of 16 pediatric patients
      treated from 1982 to 1998 by the Soft Tissue Sarcoma Italian Cooperative Group.
      PATIENTS AND METHODS: Primary surgery was conservative in all but two patients,
      and consisted of biopsy--three cases, non-radical excision--four, and radical
      resection--nine (involving a primary re-excision in 4 of 9). In two cases
      secondary radical surgery was performed after primary chemotherapy. Chemotherapy
      was administered to 9 of 16 patients, radiotherapy to three. RESULTS: After a
      median follow-up of seven years (range 3-18), the five-year event-free survival
      (EFS) and overall survival were 56.3% and 72.9%, respectively; 12 of 16 patients
      were alive (nine of them in continuos complete remission). Univariate analysis
      was performed to compare EFS according to different subgroups: size represented
      the most significant prognostic factor. CONCLUSIONS: Complete surgical resection
      is the mainstay of treatment for leiomyosarcoma. The role of both adjuvant
      chemotherapy and radiotherapy has yet to be established, and awaits cooperative
      multicentric studies.

PMID- 11583202
TI  - Transformation of Hodgkin's disease to high-grade B-cell lymphoma: remission
      after Rituximab monotherapy.
AB  - PURPOSE: We demonstrate the usefulness of immunotherapy with the CD20 antibody
      Rituximab in a case of transformation of Hodgkin's disease (HD) to high-grade non
      Hodgkin's lymphoma (NHL). CASE REPORT: A 45-year-old women suffering from
      lymphocyte predominant HD of paragranuloma type (stage IVb) since 1995 showed
      mediastinal relapse despite of 6 cycles of chemotherapy following the COPP/ABVD
      protocol in 1998. Again complete remission could be achieved after escalated BEA
      COPP II therapy in May 1998. Six months later chest radiograph and CT depicted
      pulmonary nodules. The non-typical resection of the lung revealed pulmonary
      involvement of a high-grade T-cell rich large B-cell lymphoma with 100% of the
      tumoral cells CD20 positive. Since the symptoms occurred shortly after the BEA
      COPP-escalated protocol chemotherapy resistance had to be assumed. Because of
      this problems and supported by the refusal of a high-dose chemotherapy with stem
      cell transplantation by the patient we decided to perform a mono-immunotherapy
      with the monoclonal CD20 antibody Rituximab. Today, 14 months later, the patient
      is still in complete remission including the absence of B symptoms. CONCLUSIONS:
      Immunotherapy against CD20 positive cells in cases of sequential HD and NHL seems
      to be an effective therapy in chemotherapy resistant cases because of the
      suspected clonally relation of both diseases.

PMID- 11583203
TI  - Intramedullary spinal cord metastasis (ISCM) in renal cell carcinoma: a series of
      six cases.
AB  - Intramedullary spinal cord metastasis (ISCM) has been infrequently diagnosed
      during the clinical course of renal cell carcinoma (RCC). With the advent of more
      sensitive diagnostic procedures including magnetic resonance imaging (MRI), more
      cases of ISCM have been documented. The management of these cases is particularly
      challenging as lack of prompt intervention often results in irreversible
      progressive neurological deficits. We describe the management and clinical course
      in six patients with RCC who developed ISCM. Two of these patients were treated
      surgically while four were treated with radiation therapy (RT). Although no major
      improvements in neurological function were noted, stabilizations were common.
      This prolonged their ability to live independently, a matter of utmost importance
      in these terminally ill patients.

PMID- 11583204
TI  - Meta-analyses of randomized trials of adjuvant chemotherapy in gastric cancer.

PMID- 11583205
TI  - Doxorubicin-based chemotherapy in the elderly.

PMID- 11583206
TI  - Lessons from outbreaks associated with bronchoscopy.

PMID- 11583207
TI  - Nosocomial transmission of imipenem-resistant Pseudomonas aeruginosa following
      bronchoscopy associated with improper connection to the Steris System 1
      processor.
AB  - OBJECTIVE: To assess nosocomial transmission of imipenem-resistant Pseudomonas
      aeruginosa (IRPA) following bronchoscopy during August through October 1998.
      DESIGN: Traditional and molecular epidemiological investigation of a case series.
      SETTING: University-affiliated community hospital. PATIENTS: 18 patients with
      IRPA bronchial-wash isolates. INTERVENTIONS: We reviewed clinical data, performed
      environmental cultures and molecular analysis of all IRPA isolates, and observed
      disinfection of bronchoscopes. RESULTS: Of 18 patients who had IRPA isolated from
      bronchoscopic or postbronchoscopic specimens, 13 underwent bronchoscopy for
      possible malignancy or undiagnosed pulmonary infiltrates. Following bronchoscopy,
      3 patients continued to have IRPA isolated from sputum and demonstrated clinical
      evidence of infection requiring specific antimicrobial therapy. The remaining 15
      patients had no further IRPA isolated and remained clinically well 3 months
      following bronchoscopy. Pulsed-field gel electrophoresis revealed that all
      strains except one were >95% related. STERIS SYSTEM 1 had been implemented in
      July 1998 as an automatic endoscope reprocessor (AER) for all endoscopes and
      bronchoscopes. Inspection of bronchoscope sterilization cycles revealed incorrect
      connectors joining the bronchoscope suction channel to the STERIS SYSTEM 1
      processor, obstructing peracetic acid flow through the bronchoscope lumen. No
      malfunction warning was received, and spore strips remained negative.
      CONCLUSIONS: The similarity of diverse connectors and limited training by the
      manufacturer regarding AER for bronchoscopes were the two factors responsible for
      the outbreak. Appropriate connections were implemented, and there was no further
      bronchoscope contamination. We suggest active surveillance of all bronchoscopy
      specimen cultures, standardization of connectors of various scopes and automated
      processors, and systematic education of staff by manufacturers with periodic on
      site observation.

PMID- 11583208
TI  - Pseudo-outbreak of Mycobacterium chelonae and Methylobacterium mesophilicum
      caused by contamination of an automated endoscopy washer.
AB  - OBJECTIVE: To evaluate an unusual number of rapidly growing acid-fast bacilli,
      later identified as Mycobacterium chelonae, and pink bacteria, later identified
      as Methylobacterium mesophilicum, from fungal cultures obtained by bronchoscopy.
      DESIGN: Outbreak investigation. SETTING: An academic medical center performing
      approximately 500 bronchoscopies and 4,000 gastrointestinal endoscopies in 1998.
      PATIENTS: Patients undergoing bronchoscopy July 21 to October 2, 1998. METHODS:
      The infection control department reviewed patient charts and bronchoscopy logs;
      obtained cultures of source water, faucets, washers, unopened glutaraldehyde,
      glutaraldehyde from the washers, and endoscopes; observed endoscope and
      bronchoscope cleaning and disinfecting procedures; reviewed glutaraldehyde
      monitoring records; and sent M. chelonae isolates for DNA fingerprinting.
      RESULTS: M. chelonae, M. mesophilicum, gram-negative bacteria, and various molds
      grew from endoscopes, automated washers, and glutaraldehyde from the washers but
      not from unopened glutaraldehyde. The endoscopy unit regularly monitored the pH
      of glutaraldehyde, and the logs contained no deficiencies. The above sources
      remained positive for the same organisms after a glutaraldehyde cleaning cycle of
      the automated washers. DNA finger-printing of the M. chelonae revealed that they
      were clonally related. CONCLUSIONS: The automated washers were contaminated with
      a biofilm that rendered them resistant to decontamination. The washers then
      contaminated the endoscopes and bronchoscopes they were used to disinfect. Our
      institution purchased new endoscopes and a new paracetic acid sterilization
      system.

PMID- 11583209
TI  - An episodic outbreak of genetically related Burkholderia cepacia among non-cystic
      fibrosis patients at a university hospital.
AB  - OBJECTIVE: To investigate an outbreak of Burkholderia cepacia. DESIGN:
      Observational study and chart review. PATIENTS: Adult non-cystic fibrosis (CF)
      patients. SETTING: Intensive care units (ICUs) at a university-affiliated
      teaching hospital. METHODS: As part of the epidemiological investigation, we
      conducted a chart review and collected environmental samples. A review of work
      schedules of healthcare workers also was performed. We used B. cepacia selective
      agar for preliminary screening for all isolates, which subsequently were
      confirmed as members of the B. cepacia complex by polyphasic analysis employing
      conventional biochemical reactions and genus- and species-specific polymerase
      chain reaction assays. Pulsed-field gel electrophoresis, randomly amplified
      polymorphic DNA typing, and automated ribotyping were used to genotype the
      isolates. As part of the intervention, contact isolation precautions were
      initiated for all patients identified as having had a culture positive for B.
      cepacia. RESULTS: Between September 1997 and September 1999, B. cepacia was
      isolated from 31 adult patients without CF in ICUs at a university-affiliated
      teaching hospital. Based on geographic clustering and genotypic analysis, three
      distinct clusters were observed involving 20 patients. Isolates from 17 of these
      patients were available for testing and were found to be of the same strain
      (outbreak strain). Further taxonomic analysis indicated that the outbreak strain
      was B. cepacia complex genomovar III. Twelve (71%) of the 17 patients were judged
      to be infected, and 5 (29%) were colonized with this strain. Six of 200
      environmental cultures from multiple sources in the hospital's ICUs yielded B.
      cepacia. Two of these isolates, both recovered from rooms of colonized patients,
      were the same genotype as the outbreak strain recovered from patients.
      CONCLUSION: Despite an extensive investigation, the source of the B. cepacia
      clone involved in this outbreak remains unknown. The spatial and temporal pattern
      of cases suggests that cross-transmission of a genetically related strain
      contributed to clustering among patients. The initiation of contact isolation may
      have limited the extent of this transmission. Additional studies are needed to
      elucidate better the epidemiology of nosocomial B. cepacia infection among non-CF
      adult patients.

PMID- 11583210
TI  - Burkholderia cepacia lower respiratory tract infection associated with exposure
      to a respiratory therapist.
AB  - OBJECTIVE: To investigate and control a nosocomial outbreak of Burkholderia
      cepacia lower respiratory tract infection. DESIGN: Outbreak investigation and
      case-control study. SETTING: A 260-bed community hospital. PATIENTS: Participants
      were mechanically ventilated intensive care patients without cystic fibrosis. A
      case was defined as a hospitalized patient with a sputum culture positive for B.
      cepacia between January 1 and November 6, 1998. METHODS: Respiratory therapy
      infection control policies and practices were reviewed; laboratory and
      environmental studies and a retrospective case-control study were conducted. Case
      patients were matched with control-patients on age, gender, diagnosis, and type
      of intensive care unit. RESULTS: Nine case-patients were identified; B. cepacia
      likely caused pneumonia in seven and colonization in two. Two respiratory therapy
      practices probably contributed to the transmission of B. cepacia: multidose
      albuterol vials were used among several patients, and nebulizer assemblies often
      were not dried between uses. B. cepacia was grown from cultures of three
      previously opened multidose vials; pulsed-field gel electrophoresis patterns of
      B. cepacia from seven case-patients and two multidose vials were
      indistinguishable. Case-patients had longer durations of heated humidified
      mechanical ventilation (mean, 9.8 days vs 4.4 days; P=.03) and were more likely
      to have exposure to one particular respiratory therapist than controls (odds
      ratio, undefined; 95% confidence interval, 4.7-infinity; P=.001). The association
      with the respiratory therapist, a temporary employee, persisted after controlling
      for duration of heated humidified ventilation. No new B. cepacia infections were
      identified after control measures were implemented. CONCLUSIONS: B. cepacia
      probably was transmitted among patients through use of extrinsically contaminated
      multidose albuterol vials. Respiratory therapy departments must pay close
      attention to infection control practices, particularly among new or temporary
      staff.

PMID- 11583211
TI  - Carriage of Staphylococcus aureus and of gram-negative bacilli resistant to third
      generation cephalosporins in cirrhotic patients: a prospective assessment of
      hospital-acquired infections.
AB  - OBJECTIVE: To study the relation between Staphylococcus aureus nasal and stool
      colonization, stool carriage of gram-negative bacilli resistant to third
      generation cephalosporins (CephR), and subsequent infections during
      hospitalization. DESIGN: Prospective study. PATIENTS: 551 cirrhotic patients with
      589 consecutive hospital stays. All patients were screened within 48 hours of
      admission; 589 nasal swabs, 417 stool specimens, and 589 urine samples were
      analyzed. RESULTS: Carriage rates were 18.8% for methicillin-sensitive S aureus
      (MSSA), 16.3% for methicillin-resistant S aureus (MRSA), and 13.7% for CephR. We
      observed 87 episodes of spontaneous bacterial peritonitis, 63 cases of
      bacteremia, and 167 urinary tract infections occurred. Only 1 case of bacteremia
      and 4 urinary tract infections due to CephR occurred in patients carrying the
      same organism in their stools. The risk of MRSA ascitic fluid infections,
      bacteremia, and urinary tract infections was 3.1% versus 1% (not significant),
      8.3% versus 0.8% (P<.001), and 11.4% versus 0.6% (P<.001) in carriers and
      noncarriers, respectively. Pulsed-field gel electrophoresis (PFGE) of isolates
      from 16 patients infected by MSSA (3 cases) and MRSA (13 cases) demonstrated that
      the colonizing strains matched the invasive strains in the 3 MSSA cases and in 8
      of 13 MRSA cases. CONCLUSION: Carriage of CephR strains is not associated with
      subsequent infection by these organisms in hospitalized cirrhotic patients. In
      contrast, MRSA carriage was an important risk factor for MRSA bacteremia and
      urinary tract infection.

PMID- 11583212
TI  - Effectiveness of surveillance of central catheter-related bloodstream infection
      in an ICU in Korea.
AB  - OBJECTIVE: To determine whether surveillance and infection control interventions
      decrease the incidence of catheter-related (CR) bloodstream infections (BSIs) in
      Korea. SETTING: A medical-surgical intensive care unit (ICU) of a university
      hospital in Korea. DESIGN: The CR infection rate of the intervention period was
      compared to that of historical controls for a 4-month period. PATIENTS: All
      patients with a central venous catheter in the intensive care unit (ICU) from
      October 1998 to January 1999. METHODS: Active infection control programs were
      initiated during the intervention period. Data collected included patient
      characteristics, risk factors of CR infection, and the microbiology laboratory
      results. Laboratory-proven CR infection rates were compared between the
      intervention group and control group. RESULTS: 304 catheters were inserted into
      248 patients. The intervention group and the control group showed similar
      characteristics, but more patients in the intervention group received steroid
      therapy, and subclavian insertion was more common in the intervention group. CR
      BSI occurred in 1.3 per 1,000 catheter-days in the intervention group and 4.2 in
      the control group (binomial test, P=.14). CR infections were associated with the
      duration of ICU admission by multivariate logistic regression. CONCLUSIONS: The
      data suggested that an active infection surveillance and control program could
      reduce the rate of CR

PMID- 11583213
TI  - Costs and savings associated with infection control measures that reduced
      transmission of vancomycin-resistant enterococci in an endemic setting.
AB  - OBJECTIVE: To determine the costs and savings of a 15-component infection control
      program that reduced transmission of vancomycin-resistant enterococci (VRE) in an
      endemic setting. DESIGN: Evaluation of costs and savings, using historical
      control data. SETTING: Adult oncology unit of a 650-bed hospital. PARTICIPANTS:
      Patients with leukemia, lymphoma, and solid tumors, excluding bone marrow
      transplant recipients. METHODS: Costs and savings with estimated ranges were
      calculated. Excess length of stay (LOS) associated with VRE bloodstream infection
      (BSI) was determined by matching VRE BSI patients with VRE-negative patients by
      oncology diagnosis. Differences in LOS between the matched groups were evaluated
      using a mixed-effect analysis of variance linear-regression model. RESULTS: The
      cost of enhanced infection control strategies for 1 year was $116,515. VRE BSI
      was associated with an increased LOS of 13.7 days. The savings associated with
      fewer VRE BSI ($123,081), fewer patients with VRE colonization ($2,755), and
      reductions in antimicrobial use ($179,997) totaled $305,833. Estimated ranges of
      costs and savings for enhanced infection control strategies were $97,939 to
      $148,883 for costs and $271,531 to $421,461 for savings. CONCLUSION: The net
      savings due to enhanced infection control strategies for 1 year was $189,318.
      Estimates suggest that these strategies would be cost-beneficial for hospital
      units where the number of patients with VRE BSI is at least six to nine patients
      per year or if the savings from fewer VRE BSI patients in combination with
      decreased antimicrobial use equalled $100,000 to $150,000 per year.

PMID- 11583214
TI  - Isolation in Brazil of nosocomial Staphylococcus aureus with reduced
      susceptibility to vancomycin.
AB  - OBJECTIVE: To evaluate the possible presence of vancomycin-resistant
      Staphylococcus aureus (VRSA) in a Brazilian hospital. DESIGN: Epidemiological and
      laboratory investigation of nosocomial VRSA. METHODS: 140 methicillin-resistant S
      aureus strains isolated between November 1998 and October 1999 were screened for
      susceptibility to vancomycin. The screening was carried out by using brain-heart
      infusion agar (BHIA) supplemented with 4, 6, and 8 microg/mL of vancomycin. The
      minimum inhibitory concentration (MIC) determination was carried out as
      standardized by the National Committee for Clinical Laboratory Standards using
      the broth macrodilution, agar-plate dilution, and E-test methods. PATIENTS:
      Hospitalized patients exposed to vancomycin. RESULTS: 5 of the 140 isolates had a
      vancomycin MIC of 8 microg/mL by broth macrodilution, agar plate dilution, and E
      test methods. Four VRSA strains were isolated from patients in a burn unit who
      had been treated with vancomycin for more than 30 days, and one from an
      orthopedic unit patient who had received vancomycin treatment for 7 days. Pulsed
      field gel electrophoresis characterized four of the VRSA strains as belonging to
      the Brazilian endemic clone. All five strains were negative for vanA, vanB, and
      vanC genes by polymerase chain reaction. Transmission electron microscopy of the
      five strains revealed significantly thickened cell walls. One patient died due to
      infection caused by the VRSA strain. CONCLUSIONS: This is the first report of
      isolation of VRSA in Brazil and the first report of isolation of multiple VRSA
      strains from one facility over a relatively short period of time. This alerts us
      to the possibility that VRSA may be capable of nosocomial transfer if adequate
      hospital infection control measures are not taken.

PMID- 11583215
TI  - Use and efficacy of tuberculosis infection control practices at hospitals with
      previous outbreaks of multidrug-resistant tuberculosis.
AB  - OBJECTIVE: To evaluate the implementation and efficacy of selected Centers for
      Disease Control and Prevention guidelines for preventing spread of Mycobacterium
      tuberculosis. DESIGN: Analysis of prospective observational data. SETTING: Two
      medical centers where outbreaks of multidrug-resistant tuberculosis (TB) had
      occurred. PARTICIPANTS: All hospital inpatients who had active TB or who were
      placed in TB isolation and healthcare workers who were assigned to selected wards
      on which TB patients were treated. METHODS: During 1995 to 1997, study personnel
      prospectively recorded information on patients who had TB or were in TB
      isolation, performed observations of TB isolation rooms, and recorded tuberculin
      skin-test results of healthcare workers. Genetic typing of M tuberculosis
      isolates was performed by restriction fragment-length polymorphism analysis.
      RESULTS: We found that only 8.6% of patients placed in TB isolation proved to
      have TB; yet, 19% of patients with pulmonary TB were not isolated on the first
      day of hospital admission. Specimens were ordered for acid-fast bacillus smear
      and results received promptly, and most TB isolation rooms were under negative
      pressure. Among persons entering TB isolation rooms, 44.2% to 97.1% used an
      appropriate (particulate, high-efficiency particulate air or N95) respirator,
      depending on the hospital and year; others entering the rooms used a surgical
      mask or nothing. We did not find evidence of transmission of TB among healthcare
      workers (based on tuberculin skin-test results) or patients (based on
      epidemiological investigation and genetic typing). CONCLUSIONS: We found problems
      in implementation of some TB infection control measures, but no evidence of
      healthcare-associated transmission, possibly in part because of limitations in
      the number of patients and workers studied. Similar evaluations should be
      performed at hospitals treating TB patients to find inadequacies and guide
      improvements in infection control.

PMID- 11583216
TI  - Evaluating sharps safety devices: meeting OSHA's intent. Occupational Safety and
      Health Administration.
AB  - The Occupational Safety and Health Administration (OSHA) revised the Bloodborne
      Pathogen Standard and, on July 17, 2001, began enforcing the use of appropriate
      and effective sharps devices with engineered sharps-injury protection. OSHA
      requires employers to maintain a sharps-injury log that records, among other
      items, the type and brand of contaminated sharps device involved in each injury.
      Federal OSHA does not require needlestick injury rates to be calculated by brand
      or type of device. A sufficient sample size to show a valid comparison of safety
      devices, based on injury rates, is rarely feasible in a single facility outside
      of a formal research trial. Thus, calculations of injury rates should not be used
      by employers for product evaluations to compare the effectiveness of safety
      devices. This article provides examples of sample-size requirements for
      statistically valid comparisons, ranging from 100,000 to 4.5 million of each
      device, depending on study design, and expected reductions in needlestick injury
      rates.

PMID- 11583217
TI  - The role of the laboratory in infection prevention and control programs in long
      term-care facilities for the elderly.
AB  - Hospital infection prevention and control programs rely extensively on diagnostic
      microbiology laboratory testing. However, specimens for microbiological
      evaluation are less likely to be obtained from elderly residents of long-term
      care facilities (LTCFs). In this article, issues regarding laboratory utilization
      and the potential role of the microbiology laboratory in infection prevention and
      control programs in LTCFs are reviewed. The role of the laboratory in infection
      surveillance, in the management of antimicrobial resistance, and in outbreak
      investigation are highlighted.

PMID- 11583218
TI  - Who should teach refractive surgery?

PMID- 11583219
TI  - Recutting the cornea versus lifting the flap: comparison of two enhancement
      techniques following laser in situ keratomileusis.
AB  - PURPOSE: To evaluate enhancement techniques following laser in situ
      keratomileusis (LASIK). METHODS: Recutting was performed on 263 eyes and the flap
      was lifted in 55 eyes that had LASIK for simple myopia or myopic astigmatism. The
      time interval between LASIK and retreatment was 340+/-46 days (range, 270 to 892
      days) in the recutting group and 215+/-36 days (range, 53 to 617 days) in the
      flap lifting group. Mean spherical equivalent refraction, refractive cylinder,
      uncorrected and best spectacle-corrected visual acuity were examined prior to,
      and 1, 3, and 6 months after retreatment. RESULTS: Seventeen eyes were lost to
      follow-up in the lifting group and 53 eyes in the recutting group. In the
      recutting group, mean spherical equivalent refraction improved from -1.48+/-1.25
      D to -0.49+/-0.88 D at 6 months. In the flap lifting group, mean spherical
      equivalent refraction improved from -1.05+/-1.49 D to -0.45+/-0.39 D at 6 months.
      Refractive cylinder did not change significantly in either group (P = .2). There
      was a significant increase in uncorrected visual acuity (UCVA) of 6/6 in each
      group. In the recutting group, UCVA of 6/6 increased from 3.8% to 65.2% at 6
      months, and in the lifting group from 3.6% to 71.1% at 6 months. In the recutting
      group, seven free flaps and three macerated flaps that required removal occurred.
      One eye in the recutting group and two in the lifting group developed significant
      epithelial ingrowth. No patient lost more than one line of best spectacle
      corrected visual acuity (BSCVA). CONCLUSION: Both procedures were safe,
      effective, and highly predictable for enhancements, but flap complications may be
      more likely with recutting.

PMID- 11583220
TI  - Phototherapeutic keratectomy in patients with recurrent corneal epithelial
      erosions.
AB  - PURPOSE: To evaluate the outcome of phototherapeutic keratectomy (PTK) in the
      management of recurrent corneal erosions, refractory to other forms of treatment.
      METHODS: Phototherapeutic keratectomy was performed on 43 eyes of 41 patients
      with recurrent corneal erosions. The corneal epithelium was debrided, and laser
      ablation was performed to a depth of 6 microm with an ablation zone of 7 to 9 mm,
      using the Technolas Keracor 117C PlanoScan excimer laser. Follow-up time was 12
      to 48 months (mean, 23.3+/-9.1 mo). RESULTS: After PTK, patients were free of
      symptoms in 31 eyes (72.1%), and eight eyes (18.6%) had occasional mild symptoms
      of irritation and photophobia upon awakening. Recurrence of painful corneal
      erosions occurred in four eyes (9.3%). After PTK retreatment, these patients did
      not report any further episodes and were free of symptoms for 12 to 30 months
      (mean, 21.0+/-7.7 mo). The mean spherical equivalent manifest refraction was
      changed by +0.15+/-0.39 D in the hyperopic direction at 1 year after PTK. Thirty
      three eyes (76.7%) were within +/-1 line of preoperative best spectacle-corrected
      visual acuity (BSCVA). BSCVA was improved by two or more lines in 10 eyes
      (23.3%). There were no significant complications. CONCLUSION: Excimer laser PTK
      with the Technolas Keracor 117C excimer laser was a safe and effective procedure
      for the treatment of recurrent corneal erosions. Excimer laser PTK can also be
      useful in improving the visual acuity in these patients. A small percentage of
      patients may require a second PTK to prevent further episodes of corneal
      erosions.

PMID- 11583221
TI  - Laser in situ keratomileusis in children 8 to 15 years old.
AB  - PURPOSE: To determine the safety, efficacy, predictability, and stability of
      laser in situ keratomileusis (LASIK) to correct high myopia or high myopic
      astigmatism in patients with high anisometropia in whom conventional treatments
      have failed. METHODS: Nine eyes of nine patients, three boys and six girls with
      high anisometropia (>3.50 D), were included in this study. Patient age was 8 to
      15 years. Minimum follow-up was 12 months. All patients were treated with the
      Chiron Technolas 217 excimer laser. RESULTS: Three months after LASIK,
      uncorrected visual acuity improved by at least five Snellen lines in all eyes.
      Three eyes (33.3%) were 20/40 or better without correction. Due to dense
      amblyopia, no eye had uncorrected visual acuity of 20/20 or better. The mean
      spherical equivalent refraction decreased from -7.66 to -0.22 D, and mean
      preoperative astigmatism decreased from -3.11 to -0.69 D. Eight eyes (88.8%) were
      within +/-1.00 D of emmetropia. Two eyes (22.2%) were within +/-0.50 D of the
      desired outcome. All patients were able to function binocularly. CONCLUSION: In
      this study of selected older children, LASIK was a safe and effective option for
      the correction of high anisometropia and for improved binocularity, when
      conventional therapies had failed. Further study is necessary to determine the
      long-term refractive stability in these young patients.

PMID- 11583222
TI  - Photorefractive keratectomy for hyperopia in 800 eyes with the Meditec MEL 60
      laser.
AB  - PURPOSE: To evaluate the refractive results of 800 hyperopic eyes undergoing PRK
      treatment. METHODS: Eight hundred hyperopic eyes were treated with PRK. An
      Aesculap-Meditec MEL 60 scanning ArF excimer laser used. Treatment Group 1
      consisted of eyes with a preoperative refractive error of +3.50 D or less (n =
      482) and Group 2, of +3.75 D or more (n = 318). RESULTS: Preoperatively, Group 1
      required an average correction of +2.88+/-1.34 D and Group 2 required +5.64+/
      2.96 D. One year after PRK, average residual correction was +1.26+/-1.24 D in
      Group 1, and in Group 2, +2.46+/-1.84 D. In Group 1, uncorrected visual acuity
      (UCVA) was 20/40 or better in 88.4% (426/482); 20/20 or better in 75.7% (365);
      2.1% (10/482) of eyes lost 2 lines, 2.1% (10/482) gained 2 lines; 3.1% (15/482)
      gained 2 or more lines of BSCVA; 74.4% (359/482) of eyes were within +/-0.50 D of
      target correction and 84.8% (408/482) were within +/-1.00 D. In Group 2, 47.5%
      (151/318) had UCVA of 20/40 or better; 34.2% (109/318) saw 20/20 or better
      uncorrected; 19.1% (61/318) lost 2 lines; 11.6% (37/318) lost 3 lines; none of
      the eyes gained 2 or more lines of BSCVA; 22.3% (71/318) were within +/-0.50 D
      and 46.8% (149/318) were within +/-1.00 D of target correction. Refractive
      stability was achieved after 6 months; a slight regression after 6 months was
      still observed. In Group 1, 10.5% (42/482) and in Group 2, 21.6% (69/318)
      complained of problems with daytime vision (glare and ghost image); during night
      driving in Group 1, 17.6% (85/482) and in Group 2, 40.5% (129/318) had problems.
      CONCLUSION: PRK with the Aesculap-Meditec MEL 60 scanning ArF excimer laser
      offered the best long-term results with +3.50 D or less preoperative refractive
      error. With higher corrections, regression, decrease in BSCVA, and daytime visual
      problems were encountered.

PMID- 11583223
TI  - Broad beam vs. flying spot excimer laser: refractive and videokeratographic
      outcomes of two different ablation profiles after photorefractive keratectomy.
AB  - PURPOSE: To assess the refractive outcomes and videokeratographic patterns in
      photorefractive keratectomy (PRK) of two last-generation excimer lasers: broad
      beam and flying spot lasers. METHODS: Forty eyes were treated for a mean myopic
      correction of -5.59+/-2.17 D with a Ladarvision excimer laser (Autonomous
      Technology Corp). We compared the refractive outcomes and the videokeratographic
      patterns with those of 40 eyes treated with the Summit Apex Plus laser (Summit
      Technology Inc) for a mean myopic correction of -5.60+/-2.24 D. RESULTS: During
      the 6-month follow-up, we found no significant difference in uncorrected and
      spectacle-corrected visual acuity, haze grade, regularity index, or decentration.
      The eyes treated by Ladarvision showed a lower refractive error at 1 month (P =
      .04), a lower incidence of central islands at 1 (P = .003) and 3 months (P =
      .04), a wider mean effective ablation area at 1 (P = .0004), 3 (P = .0000009),
      and 6 months (P = .0000000004), a less steep ablation edge at 1 (P = .0026), 3 (P
      = .015), and 6 months (P = .011). CONCLUSIONS: The small beam excimer laser
      provides better videokeratographic outcomes, which lead to quicker refractive
      stability and better visual performance.

PMID- 11583224
TI  - Two-year corneal endothelial cell assessment following INTACS implantation.
AB  - PURPOSE: To evaluate the 2-year effects of intrastromal corneal ring segments
      (INTACS) on the corneal endothelium. METHODS: Non-contact specular microscopy was
      performed as a subgroup test in a Phase III clinical trial. Endothelial cell
      images were collected before surgery and at 6, 12, and 24 months after surgery at
      the central and peripheral (6 and 10 o'clock) regions. Images were recorded and
      analyzed later by a central reading center. Cell density, coefficient of
      variation, and percent hexagonal cells were determined. RESULTS: There were no
      clinically significant changes in the endothelial cell structure at 6, 12, and 24
      months (102 eyes). There was a gain of 5 cells/mm2 (6 months) and 3 cells/mm2 (12
      months) at the central region of the cornea and a loss of 28 cells/mm2 at 24
      months. At the 6 o'clock region of the cornea, there was a loss of 0, 24, and 92
      cells/mm2 at 6, 12, and 24 months. At the 10 o'clock region of the cornea, there
      was a loss of 14, 30, and 94 cells/mm2 at 6, 12, and 24 months. INTACS did not
      statistically affect the central cell density at 6 and 12 months, however, there
      was a slight loss centrally at 24 months. At 24 months, all corneal regions had a
      slight decrease in cell density. In all eyes, mean central and peripheral
      endothelial cell counts remained above 2495 cells/mm2. Coefficient of variation
      improved and percent hexagonal cells remained unchanged. CONCLUSION: Endothelial
      cell density changes at 2 years after INTACS implantation were not clinically
      significant and endothelial cell remodeling was present.

PMID- 11583225
TI  - Effect of hyaluronic acid on corneal haze in a photorefractive keratectomy
      experimental model.
AB  - PURPOSE: To evaluate the ability of topical hyaluronic acid to decrease corneal
      opacity after excimer laser photorefractive keratectomy (PRK) in hens. METHODS:
      Twenty-four white hens underwent bilateral 193-nm excimer laser PRK to correct 
      9.00 D of myopia. One eye received postoperative treatment with topical 1%
      hyaluronic acid six times daily for 3 days; the other eye received phosphate
      buffered saline. Slit-lamp evaluation by a masked observer was performed for 6
      months after PRK, and electron microscopy was carried out at the end of the
      study. RESULTS: There were no significant differences in postoperative haze
      between the eyes treated with hyaluronic acid and those treated with phosphate
      buffered saline. CONCLUSION: Topical administration of hyaluronic acid had no
      effect on the development of corneal haze following PRK in hens.

PMID- 11583226
TI  - Keratolysis following excimer laser phototherapeutic keratectomy in a patient
      with keratoconus.
AB  - PURPOSE: We report a case of keratolysis following phototherapeutic keratectomy
      (PTK) for a subepithelial nodule in a patient with keratoconus. METHODS: A 29
      year-old male with keratoconus who became contact lens intolerant because of a
      raised subepithelial nodule was treated with excimer laser phototherapeutic
      keratectomy (PTK). RESULTS: The epithelium failed to heal postoperatively, and
      progressive keratolysis led to a central descemetocele by the eighth
      postoperative day. The patient was managed with a penetrating keratoplasty.
      CONCLUSIONS: Excimer laser phototherapeutic keratectomy has been shown to be an
      effective treatment for subepithelial nodules in patients with keratoconus.
      Rapidly progressive keratolysis is a potential complication of this procedure.

PMID- 11583227
TI  - Removal of corneal foreign bodies following laser in situ keratomileusis.
AB  - PURPOSE: To report the outcome of uncomplicated removal of corneal foreign bodies
      in patients who previously underwent laser in situ keratomileusis (LASIK).
      METHODS: Nine eyes of eight patients presented with corneal foreign bodies after
      LASIK. RESULTS: In three patients, diagnosis of corneal foreign bodies was
      delayed due to reduced pain and symptoms. Removal of foreign bodies was performed
      with no flap-related complications. Corneal wound healing was normal. Final
      visual acuity was not decreased. CONCLUSION: Corneal foreign bodies can be
      removed safely and effectively from corneas after LASIK.

PMID- 11583228
TI  - Dehiscence of radial keratotomy wounds without globe rupture following explosion
      injury.
AB  - PURPOSE: To report a case of explosive trauma to a patient with a history of
      radial keratotomy (RK), which resulted in multiple wound dehiscences but not
      globe rupture. METHODS: A 29-year-old male underwent radial keratotomy 1 year
      before he sustained facial trauma from a gasoline tank explosion. Corneal
      abrasions were treated with copious irrigation, topical antibiotics,
      corticosteroids, and scopolamine. He did not have a ruptured globe in either eye.
      RESULTS: The incision sites from radial keratotomy had evidence of anterior
      dehiscence in both eyes. One month following the injury, the patient had
      corrected visual acuity of 20/20-1 in the right eye and 20/25+1 in the left eye.
      At that time, the RK wounds were well healed with minimal irregularity over the
      incision sites. CONCLUSION: This case demonstrates the excellent recovery of
      visual acuity in a patient with a partial thickness traumatic wound rupture 12
      months following radial keratotomy.

PMID- 11583229
TI  - Multiple regression and vector analysis of LASIK for myopia and astigmatism.

PMID- 11583230
TI  - Diffuse lamellar keratitis caused by mechanical disruption of epithelium 60 days
      after LASIK.

PMID- 11583231
TI  - LASIK and optic nerve drusen.

PMID- 11583232
TI  - Highlights of the 1st International Congress of Wavefront Sensing and Aberration
      free Refractive Correction.
AB  - As we review the many new and evolving techniques for treating patients with
      customized ablation, it is obvious that there is a rapid evolution of technology
      and thought. Newly refined diagnostic technology, such as wavefront sensing, and
      more sophisticated spot laser delivery systems with eye tracking gives the
      refractive surgical team greater flexibility in tackling challenging optical
      abnormalities. These highlights of the 2000 Congress now set the stage for
      further development, outlined in the following selected papers from the 2001
      Congress.

PMID- 11583233
TI  - History and principles of Shack-Hartmann wavefront sensing.

PMID- 11583234
TI  - Wavefront data reporting and terminology.

PMID- 11583235
TI  - Influence of corneal curvature on calculation of ablation patterns used in
      photorefractive laser surgery.
AB  - PURPOSE: The aim of this work was to clarify the influence of the effective
      illumination area and possible reflection losses that occur during laser-tissue
      interaction on the modeling of profiles for customized corneal ablation, such as
      wavefront-guided treatments. METHODS: The changes of the ablation depth per laser
      pulse due to the projection of a laser spot onto the corneal front surface and
      reflection losses at the air-tissue interface were calculated. RESULTS: Moving
      with a scanning-spot from the center of the cornea toward the limbus resulted in
      an increase of the effective illumination area and reflection losses, which led
      to a decrease in the ablation depth per laser pulse. The decrease of the ablation
      depth was strongly related to the initial radiant exposure and the corneal
      curvature radius. CONCLUSIONS: The corneal front surface must be taken into
      consideration for ablation profile calculations, especially in customized
      treatments, due to the strong dependence of the ablation depth on the corneal
      curvature.

PMID- 11583236
TI  - Spot size and quality of scanning laser correction of higher order wavefront
      aberrations.
AB  - PURPOSE: To investigate the effect of laser spot size on the outcome of
      aberration correction with scanning laser corneal ablation. METHODS: Numerical
      simulation of ablation outcome. RESULTS: Correction of wavefront aberrations of
      Zernike modes from second to eighth order were simulated. Gaussian and top-hat
      beams of 0.6 to 2.0-mm full-width-half-maximum diameters were modeled. The
      fractional correction and secondary aberration (distortion) were evaluated. Using
      a distortion/correction ratio of less than 0.5 as a cutoff for adequate
      performance, we found that a 2 mm or smaller beam is adequate for
      spherocylindrical correction (Zernike second order), a 1 mm or smaller beam is
      adequate for correction of up to fourth order Zernike modes, and a 0.6 mm or
      smaller beam is adequate for correction of up to sixth order Zernike modes.
      CONCLUSIONS: Since ocular aberrations above Zernike fourth order are relatively
      insignificant, current scanning lasers with a beam diameter of 1 mm or less are
      theoretically capable of eliminating most of the higher order aberrations of the
      eye.

PMID- 11583237
TI  - The Alcon/Summit/Autonomous perspective on fixed vs. variable spot ablation.
AB  - The LADARVision system utilizes a small fixed diameter excimer laser beam coupled
      with a high fidelity eye tracking system to perform wavefront-guided refractive
      surgery. The fixed small beam provides a consistent ablation per pulse. By
      delivering many identical pulses in a predetermined pattern, which includes an
      optimized custom blend zone, the laser is able to ablate complex (higher order)
      corneal shapes accurately. The closed loop eye tracking system ensures that
      accurate ablation is delivered to the right place on the eye.

PMID- 11583238
TI  - The VISX perspective on fixed vs. variable spot scanning ablation.

PMID- 11583239
TI  - Aberrations and visual performance following standard laser vision correction.
AB  - PURPOSE: To relate the change of ocular aberrations with the change of visual
      performance produced by standard laser in situ keratomileusis (LASIK) for myopia.
      METHODS: Aberrations and visual performance were measured before and after
      surgery in 22 eyes. Total aberrations were measured using a laser ray tracing
      technique. Corneal aberrations were obtained using a commercial videokeratoscope
      and custom software. Visual performance was evaluated in terms of best spectacle
      corrected contrast sensitivity and high-contrast visual acuity. RESULTS: The
      amount of total and corneal aberrations increased with LASIK in all except two
      eyes. In general, the total and corneal aberration patterns were well-correlated
      after LASIK. However, the anterior corneal surface alone did not capture all the
      information (ie, possible changes induced on the posterior corneal surface or
      interactions between the different ocular components), which suggests that total
      aberrations are better predictors of visual performance. The decrease of the
      modulation transfer function (both in terms of area under the curve or as a
      function of spatial frequency) with LASIK accounted for most of the decrease in
      contrast sensitivity. High-resolution visual acuity was not very sensitive to the
      LASIK-induced changes in image quality. CONCLUSION: Wavefront and total
      aberration measurements, and in particular a combination of the two techniques,
      provide useful information for understanding the optical changes induced by
      standard refractive surgery. Predictions of the change in modulation transfer
      function derived from wave aberrations matched measurements of change in contrast
      sensitivity.

PMID- 11583240
TI  - Objective measurement of wavefront aberrations with and without accommodation.
AB  - PURPOSE: The measurement of the refractive error profile is more useful than
      corneal topography in understanding the complexities of refractive surgery. We
      report on experimental studies of the spatially resolved refractometer Tracey-1,
      developed in Ukraine by IBME in medical cooperation with VEIC, Greece. METHODS:
      Ten eyes were subjected to dynamic measurement of accommodation, in order to test
      the effectiveness of Tracey refractometry. Measurements were performed in zones 0
      to 6 mm. The refractive aberrations were calculated and accommodation was
      evaluated. RESULTS: Evaluation of data shows that the instrument can effectively
      follow the dynamic change of refractive aberrations through the accommodation
      process. CONCLUSION: Clinical tests of Tracey technology demonstrated the ability
      to investigate accommodation using this instrument.

PMID- 11583241
TI  - Wavefront customized ablations with the WASCA Asclepion workstation.
AB  - PURPOSE: WASCA (Wavefront Aberration Supported Cornea Ablation) is a method for
      wavefront-guided ablation. This new method records all existing eye aberrations
      with the Asclepion Wavefront Aberrometer and calculates the customized pattern
      for laser correction. We measured the low and high order aberrations of eyes
      before and after PRK and LASIK, as well as before and after flap creation.
      METHODS: The Asclepion Shack-Hartmann aberrometer was used to measure wavefront
      aberrations. Preoperative and postoperative measurements were made following both
      PRK and LASIK performed with conventional software, modified Aberration-free
      Profile (AFA) software, and specially designed WASCA software. Surgery was
      performed with the Meditec MEL-70 G-scan excimer laser. Additionally,
      measurements were made before and after flap creation only (10 eyes). RESULTS:
      There was a significant difference between preoperative and 1-month postoperative
      high order aberrations, with notable increases following conventional PRK and
      LASIK and less increase following modified AFA PRK and LASIK. Flap creation only
      changed the higher order aberrations slightly, and caused a shift toward
      hyperopia. In the eyes that received WASCA correction with PRK or LASIK, at 3
      months postoperative the high order aberrations averaged an increase of 1.3 times
      for PRK and 1.8 times for LASIK. Both the AFA and WASCA treatments demonstrated
      improved outcomes in comparison to conventional PRK and LASIK. CONCLUSION:
      Wavefront mapping of the eye and wavefront-guided ablation with the Asclepion
      Aberrometer can be used for optimizing the results and fine-tuning visual
      performance after laser vision correction. WASCA PRK appeared to result in better
      outcomes than WASCA LASIK.

PMID- 11583242
TI  - How Alcon/Summit/Autonomous answers six important questions about their
      customized laser platform.

PMID- 11583243
TI  - Annotation: the cognitive neuroscience of face recognition: implications for
      developmental disorders.
AB  - Face recognition is often considered to be a modular (encapsulated) function.
      This annotation supports the proposal that faces are special, but suggests that
      their identification makes use of general-purpose cortical systems that are
      implicated in high-level vision and also in memory and learning more generally.
      These systems can be considered to function within two distinct cortical streams:
      a medial stream (for learning and salience of faces encountered) and a lateral
      stream (for distributed representations of visual properties and identities of
      faces). Function in the lateral stream, especially, may be critically dependent
      on the normal development of magnocellular vision. The relevance of face
      recognition anomalies in three developmental syndromes (Autism, Williams
      syndrome, and Turner syndrome) and the two-route model sketched above is
      considered.

PMID- 11583244
TI  - Block design performance in the Williams syndrome phenotype: a problem with
      mental imagery?
AB  - Williams syndrome (WS) is a rare genetic disorder which, among other
      characteristics, has a distinctive cognitive profile. Nonverbal abilities are
      generally poor in relation to verbal abilities, but also show varying levels of
      ability in relation to each other. Performance on block construction tasks
      represents arguably the weakest nonverbal ability in WS. In this study we
      examined two requirements of block construction tasks in 21 individuals with WS
      and 21 typically developing (TD) control individuals. The Squares tasks, a novel
      two-dimensional block construction task, manipulated patterns by segmentation and
      perceptual cohesiveness to investigate the first factor, processing preference
      (local or global), and by obliqueness to examine the second factor, the ability
      to use mental imagery. These two factors were investigated directly by the
      Children's Embeded Figures Test (CEFT; Witkin, Oltman, Raskin, & Karp, 1971) and
      a mental rotation task respectively. Results showed that individuals with WS did
      not differ from the TD group in their processing style. However, the ability to
      use mental imagery was significantly poorer in the WS group than the TD group.
      This suggests that weak performance on the block construction tasks in WS may
      relate to an inability to use mental imagery.

PMID- 11583245
TI  - Learning to read in Williams syndrome: looking beneath the surface of atypical
      reading development.
AB  - In this paper, we make a fundamental distinction between literacy attainment
      scores and the actual process of learning to read, and examine these two aspects
      of reading in atypical development. Reading skills in a group of children and
      adults with the genetic disorder Williams syndrome (WS) were compared to a group
      of typically developing children matched for reading age and receptive vocabulary
      scores. Study 1 focused on the product of reading and explored the relationship
      between reading, general cognition, and phonological skills. Phonological skills
      were shown to be related to individual differences in reading attainment in both
      groups, although more weakly in the WS group. Experiment 2 examined the process
      of learning to read. The two groups were taught to associate abbreviated
      spellings (cues) with spoken words. The cues differed in their phonetic closeness
      to the target words, whereas the target words differed on the semantic variable
      of imageability. Compared to controls, the WS group showed slower learning, less
      sensitivity to the phonetic quality of the cue, and reduced influence from the
      imageability of words. The results support the hypothesis that although reading
      levels in WS depend on phonological skills, the full development of their reading
      is compromised by weak semantics. The studies highlight the importance in
      atypical populations of examining both reading levels and the actual process of
      learning to read.

PMID- 11583246
TI  - Psycholinguistic markers for specific language impairment (SLI).
AB  - In this study 160 children, aged 11 years with a definite history of specific
      language impairment (SLI), completed four tasks that could be potential positive
      psycholinguistic markers for this impairment: a third person singular task, a
      past tense task, a nonword repetition task, and a sentence repetition task. This
      allowed examination of more than one type of marker simultaneously, facilitating
      both comparisons between markers and also evaluation of combinations of markers
      in relation to identifying SLI. The study also provided data regarding the
      markers in relation to nonverbal IQ, made use of new normative data on all tasks,
      and examined marker accuracy in relation to current language status. The results
      show that markers vary in accuracy, with sentence repetition (a previously unused
      marker) proving to be the most useful. This psycholinguistic marker shows high
      levels of sensitivity (90%), specificity (85%), and overall accuracy (88%), as
      well as being able to identify the majority of children whose current language
      status falls in the normal range despite a history of SLI.

PMID- 11583247
TI  - Everyday memory and cognitive ability in children born very prematurely.
AB  - In light of recent reports of episodic memory difficulties linked to early
      childhood hypoxia (Isaacs et al., 2000; Vargha-Khadem et al., 1997), preliminary
      findings of everyday memory function are reported for 20 children born at or
      before 32 weeks gestation, compared to 20 children born at term. Memory skills
      were assessed using the Rivermead Behavioural Memory Test for Children (Wilson,
      Ivani-Chalian, & Aldrich, 1991) at 5 years of age. Everyday memory problems were
      not found to be a general feature of children born prematurely, and performance
      was closely linked to receptive language ability but not general cognitive
      ability in both groups of children. Three children in the preterm group did
      obtain scores in the impaired range of the RBMT, and in two of these children
      memory impairment could not be predicted from their receptive language ability.
      This suggests an increased risk of everyday memory difficulties in populations of
      preterm children that may be enhanced in further studies by sampling children
      with greater risk of hypoxic insult.

PMID- 11583248
TI  - Dysfunctional schemas and cognitive distortions in psychopathology: a test of the
      specificity hypothesis.
AB  - This study aimed at testing whether there were different types of dysfunctional
      schemas and cognitive distortions that could help to differentiate three
      emotional/behavioural problems, i.e., anxiety, depression, and aggression, from
      each other. Five hundred and eighty-one Chinese adolescents from five mainstream
      high schools in Hong Kong were recruited and completed several self-report
      questionnaires. Bivariate correlation showed an indiscriminate pattern of
      association between dysfunctional schemas, cognitive distortions, and the three
      emotional/behavioural problems. However, when the effects of the confounding
      correlated emotional/behavioural problems were controlled in regression analysis,
      different problems did show some specific association with different types of
      dysfunctional schemas and/or cognitive distortions. Despite some inconsistency,
      these findings generally supported a specificity hypothesis. Cognitive variables
      were thus not only relevant in understanding psychopathology, but their different
      patterns of association with anxiety, depression, and aggression also supported
      the separability of these three emotional/behavioural problems, despite their
      significant correlation.

PMID- 11583249
TI  - Handedness in boys with gender identity disorder.
AB  - Handedness preference was assessed in 205 boys with gender identity disorder and
      205 clinical control boys referred for other reasons. Boys with gender identity
      disorder were significantly more likely to be left-handed than the clinical
      control boys (19.5% vs. 8.3%, respectively). The boys with gender identity
      disorder, but not the clinical control boys, also had a significantly higher rate
      of left-handedness compared to three independent, general population studies of
      nonreferred boys (11.8%; N = 14,253) by Hardyck, Goldman, and Petrinovich (1975),
      Calnan and Richardson (1976), and Eaton, Chipperfield, Ritchot, and Kostiuk
      (1996). Left-handedness appears to be a behavioral marker of an underlying
      neurobiological process associated with gender identity disorder in boys.

PMID- 11583250
TI  - The association of the dopamine D4 receptor gene (DRD4) and the serotonin
      transporter promoter gene (5-HTTLPR) with temperament in 12-month-old infants.
AB  - This study examined the association between two common polymorphisms, the
      dopamine D4 receptor (DRD4) gene and the serotonin transporter promoter (5
      HTTLPR) gene and temperament in 61 infants aged 12 months. Twenty-two infants had
      a least one copy of the 6-8 repeat DRD4 alleles (L-DRD4) and 39 had two copies of
      the 2-5 repeat allele (S-DRD4). Twenty infants were homozygous for the short form
      (s/s) of 5-HTTLPR while 41 were either heterozygous for the short and the long
      form (l/s) or were homozygous for the long form (l/l). The infants were observed
      in a series of standard temperament episodes that elicited fear, anger, pleasure,
      interest, and activity. L-DRD4 infants showed less interest in a structured block
      play situation and more activity in a free play situation. They also displayed
      less anger in an episode of mild physical restraint. Infants with s/s 5-HTTLPR
      showed less fearful distress to stranger approach and less pleasure in a
      structured play situation than infants with l/l or l/s 5-HTTLPR. Duration of
      looking during block play was affected by a significant interaction between DRD4
      and 5-HTTLPR. Shortest duration of looking was associated with the L-DRD4 and s/s
      5-HTTLPR genotypes. The implications and limitations of these findings are
      discussed.

PMID- 11583251
TI  - The predictors of unsuccessful transition to foster care.
AB  - The placement movements of 235 children entering foster care over a 12-month
      period were followed up 4 months after referral into care. Baseline and follow-up
      measures of the 170 children who were still in care at follow-up were also
      compared. Results indicated that adolescents with mental health or behavioural
      problems were the least likely to achieve placement stability or to display
      improved psychological adjustment in care. In fact, unsatisfactory transition to
      foster care was found to be so prevalent among these children that conventional
      foster family care should be considered unsuitable for them. The paper concludes
      that there is an urgent need for a wider range of alternative care options for
      the adolescent population.

PMID- 11583252
TI  - Disorganised attachment behaviour among infants born subsequent to stillbirth.
AB  - There is limited evidence that siblings of stillborn infants are more vulnerable
      to psychological problems. This case-controlled study examines the relationship
      between previous stillbirth and the next child's pattern of attachment and
      explores factors in the mother which may be associated with and which may explain
      the pattern of infant attachment. We examined 53 infants next-born after a
      stillbirth, and 53 control infants of primigravid mothers. Maternal demographic,
      psychiatric, and attachment data were collected in pregnancy, and self-report
      measures of depression collected in the first year. Infant attachment patterns to
      the mothers were assessed when the infants were 12 months old using the Ainsworth
      Strange Situation Procedure. Infants next-born after stillbirth showed
      significant increase in disorganisation of attachment to the mother compared with
      control infants (p < .04). The difference was not accounted for by differences in
      psychiatric symptoms or demography. It was strongly predicted by maternal
      unresolved status with respect to loss as measured in the Adult Attachment
      Interview, and less strongly by maternal experience of elective termination of
      pregnancy and by the mother having seen her stillborn infant. The study adds
      weight to previously reported clinical observations, that infants born after
      stillbirth may be at risk of an increase in psychological and behavioural
      problems in later childhood. The strong association between disorganisation of
      infant attachment and maternal state of mind with respect to loss suggests that
      the mother's state of mind may be causal, and raises interesting questions about
      the mechanism of intergenerational transmission. Given the existing evidence of
      later developmental problems, longer-term follow-up of these children would be
      valuable.

PMID- 11583253
TI  - Predicting early fatherhood and whether young fathers live with their children:
      prospective findings and policy reconsiderations.
AB  - This prospective study of a birth cohort addressed three questions. Which
      individual and family-of-origin characteristics predict the age at which young
      men make the transition to fatherhood? Do these same characteristics predict how
      long young men live with their child? Are individual differences in the amount of
      time fathers spend living with their child associated with the father's
      psychosocial characteristics in young adulthood? In this unique study, it was
      found that by age 26, 19% of the 499 study men had become fathers. Individual and
      family-of-origin characteristics were assessed from birth until age 15 and
      contemporaneous characteristics were assessed at age 26. Young men who
      experienced a stressful rearing environment and a history of conduct problems
      were more likely to become fathers at an early age and to spend less time living
      with their child. Of those who experienced none of the risk factors, fewer than
      10% had become fathers by age 26 compared to more than 60% of those who
      experienced five risk factors. Fathers who lived apart from their child reported
      the most social and psychological difficulties in young adulthood. These findings
      point to individual and family-of-origin characteristics that might be targeted
      in order to delay fatherhood and increase levels of paternal involvement.
      However, given their troubled life histories and poor social-psychological
      adjustment in young adulthood, some absent fathers might have difficulties
      providing positive parenting and partnering unless policy initiatives to promote
      intact families also support young fathers.

PMID- 11583255
TI  - Suprathreshold wavelet coefficient quantization in complex stimuli:
      psychophysical evaluation and analysis.
AB  - A psychophysical experiment is described that quantifies human sensitivities to
      suprathreshold distortions caused by wavelet coefficient quantization in natural
      images, and the resulting analysis is explained. The quantizer step sizes that
      cause the first three visible degradations relative to the original image are
      well predicted by exponential functions of subband standard deviation. The
      resulting root-mean-square (RMS) error in the image is constant for a spatial
      frequency and is independent of orientation. Contrast sensitivity calculations
      suggest a higher sensitivity to bands with higher energy, and threshold
      elevations for the second and third visible degradations are predicted well by
      the constant-RMS model. A quantization strategy based on the results is proposed
      for low-bit-rate applications.

PMID- 11583254
TI  - DSM-IV internal construct validity: when a taxonomy meets data.
AB  - The use of DSM-IV based questionnaires in child psychopathology is on the
      increase. The internal construct validity of a DSM-IV based model of ADHD, CD,
      ODD, Generalised Anxiety, and Depression was investigated in 11 samples by
      confirmatory factor analysis. The factorial structure of these syndrome
      dimensions was supported by the data. However, the model did not meet absolute
      standards of good model fit. Two sources of error are discussed in detail:
      multidimensionality of syndrome scales, and the presence of many symptoms that
      are diagnostically ambiguous with regard to the targeted syndrome dimension. It
      is argued that measurement precision may be increased by more careful
      operationalisation of the symptoms in the questionnaire. Additional approaches
      towards improved conceptualisation of DSM-IV are briefly discussed. A sharper DSM
      IV model may improve the accuracy of inferences based on scale scores and provide
      more precise research findings with regard to relations with variables external
      to the taxonomy.

PMID- 11583256
TI  - Perception of forbidden colors in retinally stabilized equiluminant images: an
      indication of softwired cortical color opponency?
AB  - In color theory and perceptual practice, two color naming combinations are
      forbidden-reddish greens and bluish yellows-however, when multicolored images are
      stabilized on the retina, their borders fade and filling-in mechanisms can create
      forbidden colors. The sole report of such events found that only some observers
      saw forbidden colors, while others saw illusory multicolored patterns. We found
      that when colors were equiluminant, subjects saw reddish greens, bluish yellows,
      or a multistable spatial color exchange (an entirely novel perceptual phenomena);
      when the colors were nonequiluminant, subjects saw spurious pattern formation. To
      make sense of color opponency violations, we created a soft-wired model of
      cortical color opponency (based on winner-take-all competition) whose opponency
      can be disabled.

PMID- 11583257
TI  - Perception of spatiotemporal random fractals: an extension of colorimetric
      methods to the study of dynamic texture.
AB  - Recent work establishes that static and dynamic natural images have fractal-like
      l/falpha spatiotemporal spectra. Artifical textures, with randomized phase
      spectra, and 1/falpha amplitude spectra are also used in studies of texture and
      noise perception. Influenced by colorimetric principles and motivated by the
      ubiquity of 1/falpha spatial and temporal image spectra, we treat the spatial and
      temporal frequency exponents as the dimensions characterizing a dynamic texture
      space, and we characterize two key attributes of this space, the spatiotemporal
      appearance map and the spatiotemporal discrimination function (a map of MacAdam
      like just-noticeable-difference contours).

PMID- 11583258
TI  - Contour interaction for an easily resolvable stimulus.
AB  - It is well known that adjacent contours can reduce the visual acuity of single
      letters. Although this has traditionally been considered only in terms of a
      neural-based interaction, it has recently been suggested that the information
      content in the stimulus may account for the interaction. Here we ask the
      question, "Do similar interference effects occur for the discrimination of low
      contrast letters whose size is larger than that corresponding to the resolution
      limit?" If so, previous acuity-based interaction results may be of more general
      importance. We show that while there are interference effects of nearby contours,
      they are of a form different from that observed at the resolution limit. In
      particular, the contrast polarity of the nearby contour is unimportant, which in
      turn suggests that a physical explanation is inappropriate. Also, the
      discrimination of an easily resolvable, unflanked Landolt C target requires
      information over a much wider spatial-frequency range than its counterpart at the
      resolution limit.

PMID- 11583259
TI  - Increments and decrements in color constancy.
AB  - The present study examines whether increment-decrement asymmetries reported in a
      number of recent center-surround situations occur in more complex images as well.
      Subjects saw the CRT simulation of a whole uniformly illuminated array of
      foreground surfaces presented against a large background surface and, for a
      number of different viewing contexts, made achromatic settings over a wide range
      of luminance values. Three results emerged. First, subjects' achromatic loci did
      not fall on a single straight line in color space but rather fell on two separate
      lines intersecting at some point in this space. Second, the intersection points
      were not identical to but dependent largely on background color and showed only
      small effects of foreground colors. Third, cone signals that were decremental
      relative to the intersection point were more responsive to illuminant changes
      than cone signals that were incremental, the latter additionally showing some
      variation with foreground colors. The results are interpreted in terms of
      increment-decrement asymmetries. They suggest that these asymmetries occur in
      more complex images as well.

PMID- 11583261
TI  - On the relationship between radiance and irradiance: determining the illumination
      from images of a convex Lambertian object.
AB  - We present a theoretical analysis of the relationship between incoming radiance
      and irradiance. Specifically, we address the question of whether it is possible
      to compute the incident radiance from knowledge of the irradiance at all surface
      orientations. This is a fundamental question in computer vision and inverse
      radiative transfer. We show that the irradiance can be viewed as a simple
      convolution of the incident illumination, i.e., radiance and a clamped cosine
      transfer function. Estimating the radiance can then be seen as a deconvolution
      operation. We derive a simple closed-form formula for the irradiance in terms of
      spherical harmonic coefficients of the incident illumination and demonstrate that
      the odd-order modes of the lighting with order greater than 1 are completely
      annihilated. Therefore these components cannot be estimated from the irradiance,
      contradicting a theorem that is due to Preisendorfer. A practical realization of
      the radiance-from-irradiance problem is the estimation of the lighting from
      images of a homogeneous convex curved Lambertian surface of known geometry under
      distant illumination, since a Lambertian object reflects light equally in all
      directions proportional to the irradiance. We briefly discuss practical and
      physical considerations and describe a simple experimental test to verify our
      theoretical results.

PMID- 11583260
TI  - Veridicality of three-dimensional shape perception predicted from amplitude
      spectra of natural textures.
AB  - We show that the amplitude spectrum of a texture pattern, regardless of its phase
      spectrum, can be used to predict whether the pattern will convey the veridical
      three-dimensional (3-D) shape of the surface on which it lies. Patterns from the
      Brodatz collection of natural textures were overlaid on a flat surface that was
      then corrugated in depth and projected in perspective. Perceived ordinal shapes,
      reconstructed from a series of local relative depth judgments, showed that only
      about a third of the patterns conveyed veridical shape. The phase structure of
      each pattern was then randomized. Simulated concavities and convexities were
      presented for both the Brodatz and the phase-randomized patterns in a global
      shape identification task. The concordance between the shapes perceived from the
      Brodatz patterns and their phase-randomized versions was 80-88%, showing that the
      capacity for a pattern to correctly convey concavities and convexities is
      independent of phase information and that the amplitude spectrum contains all the
      information required to determine whether a pattern will convey veridical 3-D
      shape. A measure of the discrete oriented energy centered on the axis of maximum
      curvature was successful in identifying textures that convey veridical shape.

PMID- 11583262
TI  - Physics-based approach to color image enhancement in poor visibility conditions.
AB  - Degradation of images by the atmosphere is a familiar problem. For example, when
      terrain is imaged from a forward-looking airborne camera, the atmosphere
      degradation causes a loss in both contrast and color information. Enhancement of
      such images is a difficult task because of the complexity in restoring both the
      luminance and the chrominance while maintaining good color fidelity. One
      particular problem is the fact that the level of contrast loss depends strongly
      on wavelength. A novel method is presented for the enhancement of color images.
      This method is based on the underlying physics of the degradation process, and
      the parameters required for enhancement are estimated from the image itself.

PMID- 11583263
TI  - Fusion and merging of multispectral images with use of multiscale fundamental
      forms.
AB  - A new multispectral image wavelet representation is introduced, based on
      multiscale fundamental forms. This representation describes gradient information
      of multispectral images in a multiresolution framework. The representation is, in
      particular, extremely suited for fusion and merging of multispectral images. For
      fusion as well as for merging, a strategy is described. Experiments are performed
      on multispectral images, where Landsat Thematic Mapper images are fused and
      merged with SPOT Panchromatic images. The proposed techniques are compared with
      wavelet-based techniques described in the literature.

PMID- 11583264
TI  - Fractional Fourier transform for quasi-periodic Bloch functions.
AB  - The fractional Fourier transform (FRFT) for quasi-periodic Bloch functions is
      studied. An isomorphism between square-integrable functions on the real line and
      quasi-periodic Bloch functions is used to extend existing work on the fractional
      Fourier transform for the former functions to the latter. The properties of the
      FRFT for quasi-periodic Bloch functions are discussed, and various numerical
      examples are presented.

PMID- 11583265
TI  - Wigner function for nonparaxial wave fields.
AB  - The generalized optical transfer function and the spectral correlation function
      are investigated for nonparaxial two-dimensional wave fields. The angle-impact
      marginal of the four-dimensional Wigner function is derived directly. For focused
      wave fields of semiangle greater than 90 degrees, the spectral correlation
      function exhibits overlapping and interference. For focused wave fields for which
      the semiangle is known to be less than 180 degrees, the magnitude and phase can
      be recovered directly from knowledge of the intensity in the focal region.

PMID- 11583266
TI  - Algorithm based on rigorous coupled-wave analysis for diffractive optical element
      design.
AB  - Diffractive optical element design is an important problem for many applications
      and is usually achieved by the Gerchberg-Saxton or the Yang-Gu algorithm. These
      algorithms are formulated on the basis of monochromatic wave propagation and the
      far-field assumption, because the Fourier transform is used to model the wave
      propagation. We propose an iterative algorithm (based on rigorous coupled-wave
      analysis) for the design of a diffractive optical element. Since rigorous coupled
      wave analysis (instead of Fourier transformation) is used to calculate the light
      field distribution behind the optical element, the diffractive optical element
      can thus be better designed. Simulation results are provided to verify the
      proposed algorithm for designing a converging lens. Compared with the well-known
      Gerchberg-Saxton and Yang-Gu algorithms, our method provides 7.8% and 10.8%,
      respectively, improvement in converging the light amplitude when a microlens is
      desired. In addition, the proposed algorithm provides a solution that is very
      close to the solution obtained by the simulated annealing method (within 1.89%
      error).

PMID- 11583267
TI  - Radiometry and wide-angle wave fields III: partial coherence.
AB  - The analogs of the generalized radiances introduced in two previous manuscripts
      [J. Opt. Soc. Am. A 18, 902 (2001) and J. Opt. Soc. Am. A 18, 910 (2001)] for
      fully coherent fields in two- and three-dimensional free space are given here for
      the case of partial coherence. These functions are exactly conserved along rays
      and are suitable for the description of fields with components propagating in any
      direction. Also defined here is a global measure of coherence, which can be
      expressed in terms of the new functions. The cases of radiation in a blackbody
      cavity and partially coherent focused waves are considered as examples.

PMID- 11583268
TI  - Light scattering on hexagonal ice columns.
AB  - Light scattering on finite dielectric cylinders having noncircular cross sections
      has become of growing importance in remote-sensing applications. For analyzing
      their scattering characteristics at moderate size parameters, i.e., at a region
      where ray-tracing techniques fail, a few methods have been developed, among which
      an approximation based on the generalized separation-of-variables method has
      become very successful. This approach reveals two interesting features, which we
      discuss, that reduce the numerical effort drastically if applied to hexagonal (in
      general, 2n-periodic) boundary surfaces. Finally, some results for the phase
      function of hexagonal ice columns are given.

PMID- 11583269
TI  - Numerical studies of backscattering enhancement of electromagnetic waves from two
      dimensional random rough surfaces with the forward-backward/novel spectral
      acceleration method.
AB  - The forward-backward method with a novel spectral acceleration algorithm (FB/NSA)
      has been shown to be a highly efficient O(Ntot) iterative method of moments,
      where Ntot is the total number of unknowns to be solved, for the computation of
      electromagnetic (EM) wave scattering from both one-dimensional and two
      dimensional (2-D) rough surfaces. The efficiency of the method makes studies of
      backscattering enhancement from moderately rough impedance surfaces at large
      incident angles tractable. Variations in the characteristics of backscattering
      enhancement with incident angle, surface impedance, polarization, and surface
      statistics are investigated by use of the 2-D FB/NSA method combined with
      parallel computing techniques. The surfaces considered are Gaussian random
      processes with an isotropic Gaussian spectrum and root-mean-square surface
      heights and slopes ranging from 0.5 lambda to lambda and from 0.5 to 1.0,
      respectively, where lambda is the EM wavelength in free space. Incident angles
      ranging from normal incidence up to 70 degrees are considered in this study. It
      is found that backscattering enhancement depends strongly on all parameters of
      interest. America

PMID- 11583270
TI  - Optimal wave-front reconstruction strategies for multiconjugate adaptive optics.
AB  - We propose an optimal approach for the phase reconstruction in a large field of
      view (FOV) for multiconjugate adaptive optics. This optimal approach is based on
      a minimum-mean-square-error estimator that minimizes the mean residual phase
      variance in the FOV of interest. It accounts for the C2n profile in order to
      optimally estimate the correction wave front to be applied to each deformable
      mirror (DM). This optimal approach also accounts for the fact that the number of
      DMs will always be smaller than the number of turbulent layers, since the C2n
      profile is a continuous function of the altitude h. Links between this optimal
      approach and a tomographic reconstruction of the turbulence volume are
      established. In particular, it is shown that the optimal approach consists of a
      full tomographic reconstruction of the turbulence volume followed by a projection
      onto the DMs accounting for the considered FOV of interest. The case where the
      turbulent layers are assumed to match the mirror positions [model-approximation
      (MA) approach], which might be a crude approximation, is also considered for
      comparison. This MA approach will rely on the notion of equivalent turbulent
      layers. A comparison between the optimal and MA approaches is proposed. It is
      shown that the optimal approach provides very good performance even with a small
      number of DMs (typically, one or two). For instance, good Strehl ratios (greater
      than 20%) are obtained for a 4-m telescope on a 150-arc sec x 150-arc sec FOV by
      using only three guide stars and two DMs.

PMID- 11583271
TI  - Methods for correcting tilt anisoplanatism in laser-guide-star-based
      multiconjugate adaptive optics.
AB  - Multiconjugate adaptive optics (MCAO) is a technique for correcting turbulence
      induced phase distortions in three dimensions instead of two, thereby greatly
      expanding the corrected field of view of an adaptive optics system. This is
      accomplished with use of multiple deformable mirrors conjugate to distinct ranges
      in the atmosphere, with actuator commands computed from wave-front sensor (WFS)
      measurements from multiple guide stars. Laser guide stars (LGSs) must be used (at
      least for the forseeable future) to achieve a useful degree of sky coverage in an
      astronomical MCAO system. Much as a single LGS cannot be used to measure overall
      wave-front tilt, a constellation of multiple LGSs at a common range cannot detect
      tilt anisoplanatism. This error alone will significantly degrade the performance
      of a MCAO system based on a single tilt-only natural guide star (NGS) and
      multiple tilt-removed LGSs at a common altitude. We present a heuristic, low
      order model for the principal source of tilt anisoplanatism that suggests four
      possible approaches to eliminating this defect in LGS MCAO: (i) tip/tilt
      measurements from multiple NGS, (ii) a solution to the LGS tilt uncertainty
      problem, (iii) additional higher-order WFS measurements from a single NGS, or
      (iv) higher-order WFS measurements from both sodium and Rayleigh LGSs at
      different ranges. Sample numerical results for one particular MCAO system
      configuration indicate that approach (ii), if feasible, would provide the highest
      degree of tilt anisoplanatism compensation. Approaches (i) and (iv) also provide
      very useful levels of performance and do not require unrealistically low levels
      of WFS measurement noise. For a representative set of parameters for an 8-m
      telescope, the additional laser power required for approach (iv) is on the order
      of 2 W per Rayleigh LGS.

PMID- 11583272
TI  - Theoretical, experimental, and computational aspects of optical property
      determination of turbid media by using frequency-domain laser infrared
      photothermal radiometry.
AB  - In this work, the optical and thermal properties of tissuelike materials are
      measured by using frequency-domain infrared photothermal radiometry. This
      technique is better suited for quantitative multiparameter optical measurements
      than the widely used pulsed-laser photothermal radiometry (PPTR) because of the
      availability of two independent signal channels, amplitude and phase, and the
      superior signal-to-noise ratio provided by synchronous lock-in detection. A
      rigorous three-dimensional (3-D) thermal-wave formulation with a 3-D diffuse and
      coherent photon-density-wave source is applied to data from model phantoms. The
      combined theoretical, experimental, and computational methodology shows good
      promise with regard to its analytical ability to measure optical properties of
      turbid media uniquely, as compared with PPTR, which exhibits uniqueness problems.
      From data sets obtained by using calibrated test phantoms, the reduced optical
      scattering and absorption coefficients were found to be within 20% and 10%,
      respectively, of the values independently derived by using Mie theory and
      spectrophotometric measurements.

PMID- 11583273
TI  - Using rays better. IV. Theory for refraction and reflection.
AB  - A new ray-based method is extended to include the modeling of optical interfaces.
      The essential idea is that the wave field and its derivatives are always
      expressed as a superposition of ray contributions of flexible width. Interfaces
      can be analyzed in this way by introducing a family of surfaces that smoothly
      connects them. Even though the ray-to-wave link may appear to be obscured at
      caustics, the standard Fresnel coefficients (for plane waves at flat interfaces
      between homogeneous media) are shown to be universally applicable on a ray-by-ray
      basis. Thus, in the interaction at the interface, the surface's curvature and any
      gradients in the refractive indices influence only the higher asymptotic
      corrections. Further, this method finally gives access to such corrections.

PMID- 11583274
TI  - High-precision fringe tracking invariant to systematic model errors.
AB  - We present a new approach to processing of interferometric data, which
      dramatically improves operation on the smallest fraction of the fringe
      (approximately 1/1,000 of a wavelength and beyond). In particular, this approach,
      dubbed the variation-invariant subspace tracking approach (VISTA), makes it
      possible to operate a Michelson interferometer in a highly stable mode in which
      the estimation of optical path delay becomes invariant (insensitive) to a large
      class of systematic model errors. This previously unknown invariance property of
      interferometry follows from the fundamental odd-even symmetry of the channeled
      spectrum and its derivatives. VISTA offers a powerful algorithmic alternative for
      alleviating technological challenges in the design of high-precision long
      baseline spaceborne interferometers.

PMID- 11583275
TI  - Energy transfer at optical frequencies to silicon-based waveguiding structures.
AB  - For decades, crystalline silicon (Si) has been the semiconductor of choice for
      the majority of applications in microelectronics. Recent advances in material
      science have focused attention on the silicon-on-insulator (SOI) platform, a
      submicrometer-thick layer of single crystal Si resting on an insulating silicon
      dioxide (SiO2) layer. Here we calculate the lifetime of an electric dipole moment
      oscillating in the cover region of several canonical Si waveguiding structures.
      We show that the vicinity just above SOI produces the most dramatic changes to
      the radiative lifetime and thus the power spectrum of the emitting dipole. We
      demonstrate that SOI stands apart from other Si-based optoelectronic platforms in
      its ability to transport energy, in the form of light, away from an oscillating
      electric dipole via highly localized, optical- and IR-frequency guided waves.

PMID- 11583276
TI  - Vector diffraction theory for electromagnetic waves.
AB  - The scalar Huygens-Fresnel principle is reformulated to take into account the
      vector nature of light and its associated directed electric and magnetic fields.
      Based on Maxwell's equations, a vector Huygens secondary source is developed in
      terms of the fundamental radiating units of electromagnetism: the electric and
      magnetic dipoles. The formulation is in terms of the vector potential from which
      the fields are derived uniquely. Vector wave propagation and diffraction
      formulated in this way are entirely consistent with Huygens's principle. The
      theory is applicable to apertures larger than a wavelength situated in dark,
      perfectly absorbing screens and for points of observation in the right half-space
      at distances greater than a wavelength beyond the aperture. Alternatively, a
      formulation in terms of the fields is also developed; it is referred to as a
      vector Huygens-Fresnel theory. The proposed method permits the determination of
      the diffracted electromagnetic fields along with the detected irradiance.

PMID- 11583277
TI  - Bessel pulse beams and focus wave modes.
AB  - Free-space propagation of ultrashort pulses is investigated. Space-time couplings
      are reduced for a particular form of beams that is termed a pulse beam, or a type
      3 pulsed beam. General conditions for the formation of pulse beams in the
      paraxial approximation are presented. The free-space propagation of spatially
      localized ultrashort laser pulses is investigated. This treatment is based on a
      particular pulsed form of the well-known Bessel beam, which is termed a Bessel
      pulse beam. The connections with focus wave modes and X waves are discussed.

PMID- 11583278
TI  - New formalism for the analysis of polarization evolution for radiation in a
      weakly nonuniform, fully anisotropic medium: a magnetized plasma.
AB  - The evolution equation is obtained for the state of polarization of partially
      polarized radiation propagating in a medium that is nonuniform and fully
      anisotropic, i.e., that presents both linear and circular birefringence as well
      as dichroism. The treatment covers the general case in which the characteristic
      polarizations are not necessarily orthogonal, such as occurs for propagation in a
      magnetized, dissipative plasma. The differential Mueller matrix that appears in
      the evolution equation is obtained explicitly for two particular cases. The
      resulting formalism is convenient for numerical integration.

PMID- 11583279
TI  - Role of light intensification by cracks in optical breakdown on surfaces.
AB  - The intensity distribution of an initially plane light wave incident on planar
      and conical surface cracks is calculated numerically by using a wave propagation
      computer code. The results show that light intensity enhancements caused by
      interference of internal reflections at the crack and the surface are very
      sensitive to the light polarization, the beam angle of incidence, and the crack
      geometry (e.g., crack width and orientation with the surface). The light
      intensity enhancement factor (LIEF) can locally reach 2 orders of magnitude for
      conical cracks of ideal shape. The electric field direction relative to the crack
      surfaces determines the light intensity profile around the crack. For normal
      incidence illumination on the output surface, total internal reflection at the
      crack and the surface can occur and leads to higher LIEFs. For identical geometry
      and illumination conditions, a crack located on the entrance surface of an optic
      generates electric field enhancements that are weaker than those on the exit
      surface. As cracks on polished surfaces are randomly oriented, the probability
      for large intensity enhancements to occur is high. The model is able to predict
      quantitatively the magnitude of surface laser-induced damage threshold drop and
      damage propagation enhancement in dielectric materials that are due to cracks.

PMID- 11583280
TI  - General theory of sub-quarterwave multilayers with highly absorbing materials.
AB  - A general theory of multilayers with enhanced reflectance has been developed
      based on the superposition of sub-quarterwave layers of various highly radiation
      absorbing materials. The theory has been developed by second-order expansion of
      the multilayer reflectance with respect to the optical-constant differences
      between the materials in the multilayer. The current paper completes and improves
      the theory that was developed in a previous paper [J. Opt. Soc. Am. A 18, 1406
      (2001)] by including the case of nonnormal incidence and general radiation
      polarization and by providing more-accurate film thickness values of the
      optimized multilayer than with the previous theory. The theory provides an
      accurate approach to the design of a new concept of multilayer coatings with more
      than two materials. The new multilayers are adequate to enhance the reflectance
      of the materials particularly in the far and the extreme ultraviolet.

PMID- 11583281
TI  - Paraxial wave equation for the extraordinary-mode beam in a uniaxial crystal.
AB  - With reference to the analysis contained in J. Opt. Soc. Am. 73, 920 (1983),
      certain comments on and clarifications of the paraxial wave equation pertaining
      to the extraordinary-mode beam propagating obliquely to the optic axis in a
      uniform uniaxial crystal are presented.

PMID- 11583282
TI  - G1 phase of the cell cycle control and lung cancer: biological and clinical
      implications. Minireview.
AB  - Neoplastic diseases, including lung cancer are characterized by an uncoordinated
      cell growth. Cellular proliferation follows an orderly progression through the
      cell cycle, which is governed by protein complexes composed of cyclins and cyclin
      dependent kinases. These complexes exert their regulatory function by
      phosphorylation of key proteins involved in cell cycle transitions. Abnormalities
      of cyclins and cyclin-dependent kinases have been reported and proposed to be
      oncogenic events. It appears that the molecular networking of these proteins and
      complexes exerts an impact on two fundamental cell cycle regulators; p53 and pRb.
      Interactions between these two nuclear proteins are being delineated, implying
      potential links between p53 and Rb in cell cycle control, apoptosis, and tumor
      progression. Furthermore, the detection of alterations in p53 and Rb pathways
      appears to be of clinical significance.

PMID- 11583283
TI  - Shifts in expression of immunological cell markers in relapsed acute leukemia.
AB  - The immunophenotypic features of leukemia blast cells were analyzed in a group of
      156 patients with different immunological subtypes of acute leukemia, both
      lymphoblastic and myeloblastic. Of the 58 patients for whom immunologic studies
      were performed at relapse, 42 (72%) showed changes in the expression of
      immunologic markers. The minor shifts in B-ALL were observed most frequently and
      concerned of the loss of CD34 antigen in 17 cases and the loss of cALLA (CD10) in
      7 cases of B-ALL at the first relapse. The acquisition of cell markers was not
      frequently observed, only in four cases could be seen. HLA-DR molecules remained
      relatively constant from diagnosis to relapse. In 2 from 3 T-ALL cases the loss
      of CD1 and CD2 markers, respectively, was noticed at relapse. CD5 and CD7 markers
      were relatively stable. In AML cases at relapse the acquisition of CD13 marker
      (in 4 from 7 cases) was often observed. It was interesting that comparing to the
      B-ALL cases, the loss of CD34 marker in AML cases was stray. In one case the
      acquisition of this antigen at relapse was actually observed. The major
      interlineage shift was detected in one case of B-ALL, that was newly diagnosed at
      relapse as AML M4 and presented different cytogenetic features. This case
      provides strong connection with the treatment, as more recently
      epipodophyllotoxins (vumon in our patient) have been linked to the development of
      secondary AML associated with a shorter latency period. The immunophenotypic
      changes frequently occur at relapse in all acute leukemia types. The shifts (loss
      or acquisition) in expression of individual markers at relapse are bound with the
      first diagnosis and may have a relationship to the treatment and are important
      for correct assessment of minimal residual disease.

PMID- 11583284
TI  - Blood monocytes and tumor-associated macrophages in human cancer: differences in
      activation levels.
AB  - This study was performed to investigate functional properties of mononuclear
      phagocytes isolated from ascitic fluid in patients with peritoneal carcinomatosis
      (PC), and potential immunomodulatory effects of soluble factors produced or
      induced by human metastatic malignant cells. Phagocytic activity and nitric oxide
      production of peripheral blood monocytes (PBMo) and tumor-associated macrophages
      (TAM) or peritoneal macrophages (PEM) were synchronously examined in cancer
      patients and control individuals. Our results showed that contrary to peripheral
      blood monocytes, where phagocytic activity was not altered, TAM had impaired
      phagocytic activity. Moreover, dilutions of crude supernatant from short-term
      cultures of the peritoneal cells obtained from ascitic fluid of patient with PC,
      cause a significant, dose dependent inhibition of control PBMo and PEM
      phagocytosis, comparable to those in TAM, indicating that a soluble factor(s)
      plays a prominent role in this alteration. Next, we investigated the potential of
      cancer patients mononuclear phagocytes to produce nitric oxide (NO). It was found
      that TAM produce fourfold lower levels of NO than PEM from control subject,
      whereas monocytes produce NO at levels comparable to those of corresponding
      controls. These data support the hypothesis that depressed TAM function may
      contribute to the mechanisms of tumor escape from immune destruction.

PMID- 11583285
TI  - Therapeutic implications of the kinetics of immunomodulation during single or
      combined treatment of melanoma patients with dacarbazine and interferon-alpha.
AB  - The therapy of metastatic melanoma has not given satisfactory results. Single
      chemo- or immunotherapeutic agents in the adjuvant setting or combined
      chemoimmunotherapy for metastatic disease have generally been evaluated only in
      terms of clinical benefit. Considering that dacarbazine (DTIC) and interferon
      alpha (IFN-alpha) are among the most frequently used agents in the treatment of
      melanoma, the aim of this study was to evaluate the kinetics of immunological
      changes during adjuvant treatment of melanoma patients with DTIC or with IFN
      alpha monotherapy, as well as by their combination in metastatic disease. The
      evaluated immunological parameters showed significant early increase in the
      activity of NK (natural killer) cells, CD4/CD8 ratio, CD4+ T cell number in
      patients treated with combined chemoimmunotherapy and an increase in expression
      of the early activation antigen CD38 on CD8+ cytotoxic T cells, both, in patients
      treated with combined chemoimmunotherapy and with IFN-alpha alone, while, no
      significant change in any one parameter was detected in the group of patients
      receiving DTIC. The kinetics of the observed immunological changes, restricted to
      combined chemoimmunotherapy, indicate that the engagement of antitumor immune
      response appears early but is short-lived and that this favorable effect should
      be augmented and prolonged by the timely introduction of additional
      immunomodulating agents.

PMID- 11583286
TI  - Expression of CD20 on acute lymphoblastic leukemia cells in children.
AB  - CD20 determinant expressed on B precursors is associated with regulation of
      proliferation, apoptosis and maturation of these cells. The acute lymphoblastic
      leukemia "common" type (cALL) based on expression of CD20 is subdivided in type I
      and II. However, the clinical significance of CD20 expression on cALL and
      significance of cALL type I and II discernment are not fully elucidated. The
      association of CD20 expression with the expression of multidrug resistance
      molecule (MDR), CD34, atypical immunophenotypes of leukemia cells and response to
      induction therapy were determined in the group of 147 patients with acute
      lymphoblastic leukemia (ALL) B progenitor type (ALL-proB -14 patients) and common
      type (cALL-133 patients). The expression of CD20 on leukemia cells was studied
      routinely at diagnosis before the therapy. This expression was noted on leukemia
      cells of 6 ALL-proB patients (42.8%) and 66 cALL patients (49.6%). The expression
      of CD20 showed no association with the expression of CD34, CD22 and MDR. The
      reverse association was observed between CD20 expression and the presence of co
      expression of myeloid (CD13, CD33, CD65, CD15) and T lymphoid determinants (CD2,
      CD5, CD7) on leukemia cells. The effect of induction therapy analyzed as time of
      blast cells cytoreduction in peripheral blood and time of reaching the complete
      remission showed the slower clearance of peripheral blood from blast cells
      associated with expression of CD20. There was no association of CD20 expression
      with the time of reaching the hematological remission. The above results
      suggested a "protective" role of CD20 against co-expression of other determinants
      (myeloid and lymphoid) and no association with the results of induction therapy.

PMID- 11583287
TI  - Prognostic significance of c-erbB-2 gene expression in pancreatic cancer
      patients.
AB  - Molecular methods tend to belong to the standard armamentarium of modern
      pathology. In some instances, these methods are able to identify nosological
      entities with better accuracy than conventional technique. These methods give
      useful complementary information to choose appropriate therapeutic strategy. C
      erbB-2 overexpression in pancreatic cancer vary widely between 17 to 82%. C-erbB
      2 gene is perspective target of anticancer therapies. 57 histologically confirmed
      tumors (51 pancreatic adenocarcinoma, 5 pancreatic neuroendocrine tumors and 1
      carcinoma of Vater's ampullae) were analyzed for the presence of c-erbB-2
      expression by immunohistochemistry. Correlation with time from initial symptoms
      until diagnosis, tumor size and TNM stage at diagnosis, tumor grade, type of
      operation and overall survival were investigated. C-erbB-2 overexpression was
      detected in 19.6% samples of pancreatic adenocarcinoma and in one case of Vater's
      ampullae carcinoma. C-erbB-2 overexpression was found in two of four insulinomas.
      Univariate statistical correlation stage between c-erbB-2 overexpression and time
      from initial symptoms until diagnosis, tumor size and TNM at diagnosis, tumor
      grade, type of operation and overall survival did not reach statistical
      significans in any parameter studied. C-erbB-2 oncogene was not found to be
      prognostic factor in pancreatic cancer. Its value to predict therapeutical
      response remains to be determined in prospective clinical trials.

PMID- 11583288
TI  - Basic fibroblast growth factor as a growth factor for SRV-2-infected simian
      retroperitoneal fibromatosis cells, an animal model for AIDS related Kaposi's
      sarcoma.
AB  - Basic fibroblast growth factor (bFGF) and vascular endothelial cell growth factor
      (VEGF) were demonstrated to be important factors sustaining the growth of
      Kaposi's sarcoma. RF cells were used to provide a model to study the pathogenesis
      of Kaposi's sarcoma. In this paper, we demonstrated that bFGF is present in the
      RF cells, cultured media, and tissues from monkey. The biological activities of
      bFGF on RF cells were also studied in vitro with serum-free media. The bFGF from
      serum-free-conditioned media is biologically active to stimulate RF cells in
      certain media condition. The mitogenic effect was abrogated by sheep neutralizing
      anti-bFGF antibody. Furthermore, the effect of antibody was reversed by the
      addition of exogenous bFGF. ELISA measurements indicating the growth potency of
      conditioned media correlated with the amount of bFGF in the conditioned media.
      The data from flow cytometry demonstrated the co-existence of SRV-2 and bFGF
      among RF cells and RF tissues. Immunohistochemical staining of RF tissue blocks
      for bFGF revealed that bFGF was present in the tumor and the presence of bFGF was
      not caused by the artifact of tissue culture. These results indicate that bFGF is
      an important growth factor to promote RF cell growth in vitro and RF tumor in
      vivo. Further studies are required to determine the relationship between the
      interaction of bFGF, SRV-2, and VEGF. This model also provides an adequate
      alternative to the model induced by simian immunodeficiency virus (SIV) to study
      the Kaposi's sarcoma.

PMID- 11583289
TI  - Gemcitabine and vincristine: an effective outpatient regimen with low
      myelotoxicity for stage IV non-small cell lung cancer.
AB  - The activity and tolerability of gemcitabine and the non-overlapping toxicity of
      gemcitabine plus vincristine were the basis for testing this regimen patients
      with non-small cell lung cancer (NSCLC). Forty patients (25 male/15 female,
      median age 52 years) with stage IV NSCLC and a Karnofsky Performance Status score
      > or = 60 entered the trial. Patients received gemcitabine 1000 mg/m2 on days 1,
      8 and 15 and vincristine 1.4 mg/m2 on days 1 and 15, every 4 weeks. The overall
      response rate was 16/40 (40%) (N = 40); with 2 complete and 14 partial responses;
      additional 14 patients had minor responses or stable disease. Median duration of
      remission was 4.5 months, and the median survival was 9 months. In two patients
      with grade 2 generalized vesicular rash and severe malaise, respectively,
      treatment-related toxicity led to early termination of treatment. Among patients
      treated for more than two months, vincristine doses were reduced/omitted for 55%
      of cycles because of grade 1-2 peripheral neuropathy. Myelotoxicity was frequent
      but rarely clinically significant. Mean platelet counts on day 1 of cycles 2,3
      and 4 were significantly higher than the pre-treatment or post-treatment values.
      We conclude that vincristine plus gemcitabine is an an active and well tolerated
      regimen. Its interesting "platelet-saving" effect deserves further investigation.

PMID- 11583290
TI  - Cladribine combined with mitoxantrone in the treatment of blastic phase of
      chronic myeloid leukemia.
AB  - A phase II clinical study was performed to evaluate the effectiveness and
      toxicity of cladribine (2-CdA) combined with mitoxantrone (CM regimen) in the
      treatment of chronic myeloid leukemia in blastic phase (CML BP). A total of 12
      adult patients with CML BP were included in this study. 2-CdA was given at a dose
      0.12 mg/kg in 2-hour iv infusion on days 1-5 and mitoxantrone 10 mg/m2 i.v. day
      1. The cycles were repeated at 4 week intervals in most cases. Complete remission
      (CR) was defined as the presence of < 5% of blasts in a normo- or hypercellular
      bone marrow in addition to normal peripheral blood counts and with normal
      physical examination. A partial response (PR) required normal peripheral blood
      counts but 5 to 25% marrow blasts. Toxicity was assessed according to WHO
      criteria. The patients received 21 courses of CM (median 2, range 1-3). Of 12
      patients only 2 (17%), achieved PR. Responses were observed in patients with
      myeloid BP, after 3 and 2 courses, respectively. Myelosuppression was the main
      toxicity. Four patients (33.3%) had grade 3 or 4 neutropenia and 3 (25%) had
      grade 3 or 4 thrombocytopenia. Infections occurred in 4 patients (33.3%) and 2 of
      them died of sepsis shortly after CM treatment. This preliminary results in a
      small group of patients suggest that CM programme has limited value in pre
      treated patients with CML BP. However, this regimen may be used as palliation in
      the end stage of disease.

PMID- 11583291
TI  - Non-steroidal anti-inflammatory agent ibuprofen-induced apoptosis, cell necrosis
      and cell cycle alterations in human leukemic cells in vitro.
AB  - The cytotoxic activity of the non-steroidal anti-inflammatory agent ibuprofen to
      human promyelocytic leukemia cell line HL-60, its multidrug-resistant subline HL
      60/VCR (MDR-1 gene coded P-glycoprotein), as well as myeloma U266 and B
      lymphoblastoid ARH-77 cell lines was demonstrated with the aid of flow cytometric
      analysis. Ibuprofen inhibited proliferation and induced apoptosis (detected as
      sub-G0 nuclei, fluorescein diacetate staining, Annexin-V binding cells and
      agarose electrophoretic detection of nucleosomal DNA fragmentation) in
      promyelocytic cells and, to a lesser extent, in U266 and ARH-77 cells.

PMID- 11583292
TI  - Embryotoxicity of TPPS4 and PS 3 photosensitizers in chicken embryo under
      different light conditions.
AB  - Hematoporphyrin derivatives have been recommended for photodynamic therapy of
      malignant processes. We administered TPPS4, and Photosan 3 (PS 3) in chick embryo
      in ovo, with or without subsequent blue light (400-550 nm) irradiation. The aim
      was to analyze and compare the effects of both substances on organogenesis under
      different light conditions. The embryotoxic effect (embryonic death and
      malformations) was detected after a single intra-amniotic injection of 5
      different doses (0.3 to 300 microg) of TPPS4 or PS 3 at embryonic day 3-5. The
      beginning of the embryotoxicity range (minimal embryotoxic dose) was determined
      in non-irradiated embryos to be between 0.3-3.0 microg PS 3 and 3.0-30.0 microg
      TPPS4. Malformations of surviving embryos were similar after both substances,
      represented by trunk hyperlordosis combined with incomplete closure of the
      ventral body wall and protrusion of viscera as consequences of amnion
      contraction, reduction limb deformities, eye malformations and cleft beak. Ten
      minutes light irradiation in ovo following two hours after intra-amniotic
      injection of TPPS4 or PS 3 increased by one order of magnitude their embryotoxic
      effects. Even dark-ineffective doses became highly embryotoxic. Contraction of
      the amniotic sac and extraembryonic vessels seemed to be a common mechanism of
      photosensitizer action.

PMID- 11583293
TI  - Clinical and histopathological evaluation of the adrenal incidentaloma.
AB  - Clinically silent adrenal masses (incidentaloma) are incidentally discovered
      lesions, when noninvasive imaging methods (USG, CT, MRI) are performed for
      reasons other than known or suspected adrenal disease. Most studies report on a
      prevalence of adrenal incidentaloma range between 1% and 10% in radiological
      series. Between 1994 and 1999 we observed in our Department 57 patients with
      incidentalomas of adrenal glands. After endocrinological evaluation silent
      Cushing's syndrome was found in 2 cases (3.5%). Fifty two patients were qualified
      for surgery. Adrenocortical adenoma was diagnosed in 73.1%; adrenocortical
      carcinoma in 7.7%; pheochromocytoma in 7.7% and less frequent adrenal lesions in
      11.5%. All adrenal carcinomas and malignant pheochromocytomas (11.5%) were found
      in tumors with diameter over 4 cm.

PMID- 11583295
TI  - Long-term clinical benefits of the low dose rate endobronchial irradiation of
      malignant airway obstructions.
AB  - Brachytherapy allows the delivery of higher radiation doses, possibly leading to
      improved locoregional tumor control and subsequent prolonged survival. The
      purpose of our study was to evaluate the long-term clinical survival in patients
      with malignant airway compromise treated with endobronchial brachytherapy and to
      estimate possible influence of other factors on survival and to review
      complications of the therapy. In a retrospective study 55 patients with malignant
      inoperable tracheobronchial lesions underwent 71 brachytherapy treatments with
      137Cesium. Either MicroSelectron (N=56) or Selectron (N=15) were used. All except
      4 patients received external radiation, 20 patients received chemotherapy, 37
      patients received laser excision. Major symptomatic improvement was noted in 75%
      of patients. Substantial or complete relief of hemoptysis was achieved in 85%, of
      dyspnea in 65% and of cough in 68%. Response evaluation showed no complete
      response, partial response was achieved in 70.9% and the endoscopic finding was
      not changed, or recurrence of the tumor was found in 29.1%. A relatively small
      number of complications of the endobronchial brachytherapy occured. Significant
      bleeding was observed in 1 procedure and an inability to tolerate in 3 cases. In
      2 cases, it was not possible to place an applicator due to extreme hypoxia.
      Bronchomediastinal fistula developed in 1 patient and tracheal stenosis in 1
      patient. The overall incidence of complications was 15%. The median survival from
      establishing the diagnosis was 510 days. The median survival after the first
      brachytherapy treatment was 200 days. We compared the survival in the subgroups
      of patients in relation to TNM status, chemotherapy, laser debulking
      brachytherapy device used. The stage IIIA patients survived longer from diagnosis
      than IIIB patients but the difference was on the border of significance (p =
      0.090). In the evaluation of chemotherapy, more patients survived 12 months from
      the diagnosis (p = 0.045) when treated by chemotherapy comparing to the patients
      treated without chemotherapy. However, this difference disappeared during the
      further development of the disease. In the Nd-YAG laser treatment, the patients
      treated by brachytherapy with the previous laser debulking survived significantly
      longer from the time of the first brachytherapy session (p = 0.005). No
      statistical difference was found in the survival of patients treated by either
      the Selectron or MicroSelectron device. The LDR endobronchial brachytherapy is a
      well tolerated, safe and effective technique for palliation of malignant airway
      occlusions. In our group of patients, the long-term survival was longer in IIIA
      stage comparing to the IIIB, in the group treated by the previous chemotherapy
      compared to the patients without chemotherapy and in the group with the Nd-YAG
      laser therapy, comparing to the group treated by the brachytherapy only. No
      difference of the brachytherapy device used was found.

PMID- 11583294
TI  - The differential inhibitory effects of genistein on the growth of cervical cancer
      cells in vitro.
AB  - The biological effect of genistein on cervical cancer was studied on two cervical
      cancer cell lines with different cellular characteristics. Here we report that
      genistein exhibits inhibitory effects on the growth of HeLa and ME-180 cells. The
      IC50 was 35 microM and 60 microM for HeLa and ME-180 cells, respectively. ME-180
      cells showed obvious G2/M arrest with genistein treatment while most of the HeLa
      cells were accumulated in S phase. The underlying molecular mechanism was further
      elucidated by apoptosis analysis and expression levels of cell cycle regulatory
      proteins. Treatment of the cell lines with genistein also resulted in suppression
      of invasion through a surrogate membrane in a dose-dependent manner, particularly
      the HeLa cells. While the underlying mechanism needs to be further studied, the
      higher suppressive effect on invasion of HeLa cells, an adenocarcinoma cell line,
      are noteworthy. This in vitro observation may have clinical implication to
      improve the treatment of cervical adenocarcinoma.

PMID- 11583296
TI  - Non-equilibrium thermodynamics of concentration polarization.
AB  - Ultrafiltration is a membrane separation process with many applications,
      including the treatment of industrial wastes and the processing of milk and
      juices. Academics are also interested in ultrafiltration as a possible tool for
      measuring empirical coefficients such as the diffusion coefficient and the
      permeability. One particular region of an ultrafiltration system that is not yet
      fully understood, and is related to a decline in the efficiency, is the
      concentration polarization layer, which develops as the macromolecules retained
      by the membrane form a highly concentrated layer that attempts to diffuse back
      toward the bulk of the solution. Using the postulates of classical non
      equilibrium thermodynamics, a complete model, which accounts for the fact that a
      concentration polarization layer may have properties of both a porous medium and
      a region undergoing Brownian diffusion, has been derived and applied to several
      systems from the literature.

PMID- 11583297
TI  - Conventional optical microscopy of colloidal suspensions.
AB  - Optical microscopy can resolve detail at the larger end of the colloidal length
      scale, and to image suspensions at an individual particle level of resolution
      would allow the investigation of local behaviour in a way denied to the
      established scattering techniques. However, to achieve high-contrast single
      particle resolution in dense suspensions that are thick enough to show behaviour
      the same as would be expected in the bulk is not a trivial exercise. We build on
      established advanced techniques of the conventional (i.e. non-confocal) light
      microscopy of phase objects to develop a suitable experimental protocol.
      Furthermore, we demonstrate the effectiveness of this protocol by means of an
      'atlas' of the hard-sphere crystalline solid (where random stacking results in
      many complex facets), which should serve as a compendium for future study.

PMID- 11583298
TI  - Microemulsion polymerization of styrene in the presence of a cationic emulsifier.
AB  - The principal subject discussed in the current paper is the radical
      polymerization of styrene in the three- and four component microemulsions
      stabilized by a cationic emulsifier. Polymerization in the o/w microemulsion is a
      new polymerization technique which allows to prepare the polymer latexes with the
      very high particle interface area and narrow particle size distribution. Polymers
      formed are very large with a very broad molecular weight distribution. In
      emulsion and microemulsion polymerizations, the reaction takes place in a large
      number of isolated loci dispersed in the continuous aqueous phase. However, in
      spite of the similarities between emulsion and microemulsion polymerization,
      there are large differences caused by the much larger amount of emulsifier in the
      latter process. In the emulsion polymerization there are three rate intervals. In
      the microemulsion polymerization only two reaction rate intervals are commonly
      detected: first, the polymerization rate increases rapidly with the reaction time
      and then decreases steadily. Essential features of microemulsion polymerization
      are as follows: (1) polymerization proceeds under non-stationary state
      conditions; (2) size and particle concentration increases throughout the course
      of polymerization; (3) chain-transfer to monomer/exit of transferred monomeric
      radical/radical re-entry events are operative; and (4) molecular weight is
      independent of conversion and distribution of resulting polymer is very broad.
      The number of microdroplets or monomer-starved micelles at higher conversion is
      high and they persist throughout the reaction. The high emulsifier/water ratio
      ensures that the emulsifier is undissociated and can penetrate into the
      microdroplets. The presence of a large amount of emulsifier strongly influences
      the reaction kinetics and the particle nucleation. The mixed mode particle
      nucleation is assumed to govern the polymerization process. At low emulsifier
      concentration the micellar nucleation is dominant while at a high emulsifier
      concentration the interaction-like homogeneous nucleation is operative.
      Furthermore, the paper is focused on the initiation and nucleation mechanisms,
      location of initiation locus, and growth and deactivation of latex particles.
      Furthermore, the relationship between kinetic and molecular weight parameters of
      the microemulsion polymerization process and colloidal (water/particle interface)
      parameters is discussed. In particular, we follow the effect of initiator and
      emulsifier type and concentration on the polymerization process. Besides, the
      effects of monomer concentration and additives are also evaluated.

PMID- 11583299
TI  - Acoustic and electroacoustic spectroscopy for characterizing concentrated
      dispersions and emulsions.
AB  - We describe two different techniques (acoustics and electroacoustics), both of
      which employ ultrasound instead of light for extracting information about the
      properties of liquid-based dispersions. Ultrasound can propagate through samples
      that are not transparent for light, which open up many new applications not
      possible with classical light scattering methods. Acoustic and electroacoustic
      techniques offer a unique opportunity to characterize concentrated dispersion,
      emulsions and microemulsions in their natural states. Elimination of a dilution
      step required for most other techniques (light scattering, sedimentation,
      electrophoresis) is crucial for an adequate characterization of liquid
      dispersions, especially when the high concentration leads to structured systems.
      As with any macroscopic method, ultrasonic techniques characterize the sample in
      two steps. The first step is to measure some macroscopic property. The second
      step involves some theoretical treatment of the measured raw data which yields
      the desired information. Acoustic spectroscopy deals with measuring the
      attenuation of ultrasound within a certain frequency range. Electroacoustic
      spectroscopy has two implementations depending on the driving force. We emphasize
      here on the so-called Colloid Vibration Current (CVI) which is generated by the
      sound wave as it passes through the dispersion. A review of the theoretical basis
      of acoustics and electroacoustics is given, with emphasis on models that have
      been applied to concentrated systems. Recently, new theories have been developed
      for both acoustics and electroacoustics using a 'coupled phase model' and 'cell
      model concept'. The coupled phase model is widely used for describing a relative
      motion of the particles and liquid in the sound wave. The cell model approach
      opens the way to include both particle-particle interactions and polydispersity
      into the theoretical model. Experimental evidence is presented that shows that
      this new approach is successful in concentrated systems up to 45% vol. A short
      review of the possible applications of acoustics and electroacoustics
      measurements to a range of systems is presented including: ceramics, mixed
      dispersed systems, chemical-mechanical polishing abrasives, emulsions,
      microemulsions and latex materials.

PMID- 11583300
TI  - Inherited disorders and gene regulation of platelet signal transduction: the
      picture is expanding.

PMID- 11583301
TI  - Revival of plasmin as a therapeutic agent?

PMID- 11583302
TI  - Genetic variation of the extra-large stimulatory G protein alpha-subunit leads to
      Gs hyperfunction in platelets and is a risk factor for bleeding.
AB  - Alternatively spliced GNAS1 and XL-GNAS1, encoding respectively the stimulatory G
      protein alpha-subunit (Gsalpha) and the extra-large stimulatory G-protein alpha
      subunit (XLsalpha), are located on the imprinted chromosomal region 20q13.12-13.
      We presently report a functional polymorphism in the imprinted XL-GNAS1 gene. In
      three patients, a 36 bp insertion and two basepair substitutions flanking this
      insertion were found in the paternally inherited XL-GNAS1 exon 1. They clinically
      manifest an enhanced trauma-related bleeding tendency and a variable degree of
      mental retardation. A platelet aggregation inhibition test to evaluate Gs
      function was developed. Their platelets display Gs hyperfunction and an enhanced
      cAMP generation upon stimulation of Gs-coupled receptors. The prevalence of the
      XLsalpha insertion in a normal control group was 2.2%. Normal controls,
      inheriting the insertion maternally, had a normal platelet Gs activity, whereas
      controls inheriting the insertion paternally had increased inducible platelet Gs
      activity, defining the insertion as a functional polymorphism. This paternally
      inherited XLsalpha insertion represents a new genetic cause of an inherited
      bleeding tendency, although to a variable degree.

PMID- 11583303
TI  - Plasmin induces local thrombolysis without causing hemorrhage: a comparison with
      tissue plasminogen activator in the rabbit.
AB  - The direct fibrinolytic enzyme, plasmin, was compared with tissue plasminogen
      activator (TPA) in rabbit models of local thrombolysis and fibrinolytic
      hemorrhage. Plasmin was produced by solid-phase urokinase activation of
      plasminogen and purified on benzamidine Sepharose. Applied as an intra-arterial
      infusion into the thrombosed abdominal aorta under conditions of unimpeded blood
      flow, plasmin (4 mg/kg) and TPA (2 mg/kg) achieved equivalent clot dissolution
      and flow restoration. Using the model of restricted blood flow into the
      thrombosed aorta, which limits local plasminogen supply, plasmin was superior to
      TPA in clot lysis and vascular reperfusion. Using similar dosages of plasmin (2
      or 4 mg/kg) and TPA (1 or 2 mg/kg) in the earpuncture rebleed model. TPA induced
      rebleeding in a dose-dependent manner from prior puncture sites in 9 of 10
      animals, while none of the 10 animals exposed to plasmin rebled from these sites.
      These results suggest that plasmin is an effective, unique thrombolytic agent,
      distinguished from the plasminogen activators in current usage by its striking
      safety profile.

PMID- 11583304
TI  - Adhesive interactions of leukocytes, platelets, and the vessel wall during
      hemostasis and inflammation.

PMID- 11583305
TI  - The TF:VIIa complex: clinical significance, structure-function relationships and
      its role in signaling and metastasis.

PMID- 11583306
TI  - Thrombophilic risk factors in patients with central retinal vein occlusion.
AB  - Few and contrasting data are available on the prevalence of hemostatic risk
      factors in patients with central retinal vein occlusion (CRVO). Aim of this study
      was to investigate the metabolic and inherited risk factors for venous thrombosis
      in 100 CRVO patients (age: 59 yrs; range 18-77) and in 100 controls (age: 56 yrs;
      range 18-84). In patients homocysteine (Hcy) levels were significantly higher
      than in controls and were affected by the C677T methylenetetrahydrofolate
      reductase (MTHFR) polymorphism (p < 0.001). The prevalences of activated protein
      C resistance (APCR), factor V Leiden positivity, elevated PAI-1 and Lp(a) levels
      were significantly higher in patients with respect to controls. At multivariate
      analysis, only hyperhomocysteinemia (OR 11, 95% CI 3.6-36.2; p < 0.0001) and
      elevated PAI-1 levels (OR 8.9, 95% CI 3.5-41.3; p < 0.01), in addition to
      hypertension (OR 40.5, 95% CI 8.6-188.8; p < 0.00001) and hypercholesterolemia
      (OR 3.1, 95% CI 1.6-20.5; p < 0.05), were independent risk factors for CRVO.
      These data demonstrate a potential role of hemostatic risk factors in the
      pathophysiology of CRVO.

PMID- 11583307
TI  - Increased platelet glycoprotein V levels in patients with coronary and peripheral
      atherosclerosis--the influence of aspirin and cigarette smoking.
AB  - As platelet hyperactivity is important in atherosclerosis and smoking, we
      hypothesized higher levels of soluble platelet membrane glycoprotein V (gpV) in
      95 patients with peripheral artery disease (PAD) and 92 with coronary artery
      disease (CAD) compared to 99 healthy controls, and examined the effects of
      aspirin and of smoking two cigarettes on soluble gpV and platelet function.
      Soluble gpV (ELISA) was significantly raised in, but not between, both PAD and
      CAD patients, compared to controls (p < 0.05). In multivariate analysis, systolic
      blood pressure, smoking and atherosclerosis (all p < 0.01) were significant
      influences on soluble gpV in the whole study cohort. There was a weak correlation
      between soluble gpV and another platelet marker, soluble P selectin (p = 0.048).
      Acute smoking in 14 subjects increased platelet aggregability and beta
      thromboglobulin, but not soluble gpV: there were no changes in 11 non-smokers.
      Five days consumption of aspirin (325 mg daily) by 14 subjects did not influence
      levels of soluble gpV. Our data indicate that soluble gpV may be a useful new
      marker of platelet activation in atherosclerosis, but may be influenced by
      smoking status and blood pressure.

PMID- 11583308
TI  - Flow cytometry detection of platelet procoagulation activity and microparticles
      in patients with unstable angina treated by percutaneous coronary angioplasty and
      stent implantation.
AB  - Platelet activation is known to participate to the pathogenesis of acute coronary
      syndromes. Aminophospholipid exposure and microparticles shedding are hallmarks
      of full platelet activation and may account for the dissemination of
      prothrombotic seats. Using flow cytometry analysis of annexin V binding to
      externalized aminophospholipids, we followed platelet procoagulant activity (PPA)
      and platelet microparticles (PMP) shedding in venous and coronary whole blood
      samples from 30 patients with unstable angina before and after percutaneous
      coronary angioplasty (PTCA) and stent implantation. Baseline values of PPA and
      PMP were significantly more elevated in patients than in control subjects (p <
      0.005). PMP percentage was significantly higher in coronary than in venous blood,
      and in coronary blood of patients with proximal instead of mid/distal lesions of
      coronary arteries. No enhancement of platelet reactivity to TRAP and collagen was
      induced by procedure. Whereas activated GpIIb-IIIa and P-selectin expression
      decreased 24 h and 48 h after procedure, PPA and PMP remained as elevated as
      before. Thus, flow cytometry is a reliable method for detection of fully
      activated platelets in whole blood samples. Annexin V binding analysis
      demonstrates the persistance of in vivo platelet activation, despite the use of
      antiaggregating agents.

PMID- 11583309
TI  - Increased level of von Willebrand factor is significantly and independently
      associated with diabetes in postinfarction patients. THROMBO Investigators.
AB  - Diabetes is an established risk factor for reinfarction and cardiac death in
      postinfarction patients. Since the underlying mechanism of diabetes-related risk
      is not fully understood we aimed to evaluate the association between lipids,
      thrombogenic factors and diabetes in postinfarction patients. The study
      population consisted of 1,045 postinfarction patients (846 non-diabetic, 125 non
      insulin- and 74 insulin-requiring diabetics) with the following blood tests
      performed 2 months after an index myocardial infarction: lipoprotein (a),
      apolipoprotein-B, apolipoprotein-A, cholesterol, HDL cholesterol, triglycerides,
      insulin, von Willebrand factor (vWF), fibrinogen, factor VII, D-dimer, and
      plasminogen activator inhibitor (PAI-1). After adjustment for relevant clinical
      covariates, non-insulin-requiring diabetes was significantly (p < 0.05)
      associated with elevated levels of (odd ratios per 1 log unit increase in
      parenthesis) vWF (1.74) and PAI-1 (1.42) whereas insulin requiring diabetes was
      associated with even more elevated levels of vWF (4.68), but not with increased
      levels of PAI-1. No significant differences in lipid levels were observed among
      three groups. In conclusion, increased level of von Willebrand factor is
      significantly and independently associated with diabetes in postinfarction
      patients, suggesting that endothelial damage is the primary mechanisms
      contributing to an increased occurrence of vascular and cardiac events in
      diabetic postinfarction patients.

PMID- 11583310
TI  - Risk of pregnancy-related venous thrombosis in carriers of severe inherited
      thrombophilia.
AB  - Homozygous carriers of factor V Leiden have an approximately 80-fold increased
      risk of venous thrombosis. Also double heterozygous carriers of both the factor V
      Leiden and the prothrombin gene mutations are at high thrombotic risk. The
      magnitude of the risk of venous thrombosis in pregnant women with the two severe
      thrombophilic conditions has not been estimated so far. We performed a
      multicenter retrospective family study in women with homozygous factor V Leiden,
      double heterozygous factor V Leiden and the prothrombin gene mutation, and women
      with normal coagulation. Only relatives of index patients with thrombosis formed
      the study cohort. Fifteen homozygous and 39 double heterozygous women were
      compared to 182 women with normal coagulation. Venous thrombosis occurred in 3 of
      19, 2 of 50 and 1 of 221 pregnancies, respectively. One thrombotic episode
      occurred in the third trimester, the remaining 5 in the postpartum. The
      prevalence of venous thrombosis was 15.8% (95% CI 3.4-39.6) for homozygotes. 4.0%
      (95% CI 0.5-13.7) for double heterozygotes and 0.5% for women with normal
      coagulation. The relative risk of pregnancy-related venous thrombosis was 41.3
      (95% CI 4.1-419.7) for homozygous and 9.2 (95% CI 0.8-103.2) for double
      heterozygous carriers. In conclusion, homozygous carriers of factor V Leiden and,
      to a lesser extent, double heterozygous carriers of factor V Leiden and of the
      prothrombin mutation have an increased risk of venous thrombosis during
      pregnancy, particularly high during the postpartum period. On the basis of these
      findings we recommend that these women receive anticoagulant prophylaxis at least
      in the postpartum, that should perhaps be extended to the whole pregnancy in
      homozygous carriers.

PMID- 11583311
TI  - Phenotypic APC resistance in carriers of the A20210 prothrombin mutation is
      associated with an increased risk of venous thrombosis.
AB  - We hypothesized that increased prothrombin levels associated with G20210A
      prothrombin gene mutation could affect the results of activated protein C (APC)
      resistance phenotype and increase the risk of venous thrombosis (VT). The
      increasing addition of purified prothrombin in plasma of 90 normal subjects
      resulted in a parallel significant increase of APC resistance. Significantly
      different mean n-APC-SR in 879 GG20210 subjects compared to 27 heterozygous
      carriers of isolated G20210A mutation was observed (1.0 +/- 0.12 vs. 0.95 +/-
      0.11; P = 0.02) in a random sample of 906 normal population subjects. Twenty
      seven families with VT and isolated G20210A mutation consecutively diagnosed
      during 1998-1999 were evaluated. Mean n-APC-SR was significantly lower in the 80
      G20210A carriers compared to 58 GG 20210 relatives investigated, even after sex
      and age adjustment (0.92 +/- 0.08 vs. 1.05 +/- 0.13; P < 0.0001). A strong
      relationship between plasma prothrombin level and n-APC-SR was observed in the
      families. When n-APC-SR values were grouped in tertiles, the odds ratio for VTE,
      after exclusion of the index cases and adjustment for 20210 status, for subjects
      in the lowest tertile (n-APC-SR 0.73-0.90) was 4.58 (95% CI 0.78-26.88) compared
      to upper tertile (n-APC-SR 1.01-1.30). In conclusion, in subjects with G20210A
      mutation APC resistance is significantly increased, correlates with plasma
      prothrombin level and the carriers with the lowest APC resistance values have an
      increased risk of VTE.

PMID- 11583312
TI  - Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous
      thromboembolism--pooled analysis of 8 case-control studies including 2310 cases
      and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism.
AB  - Factor V Leiden and factor II G20210A mutations are two frequent genetic risk
      factors involved in venous thromboembolism (VTE). The goal of this pooled
      analysis of 8 case-control studies, comprising a total of 2310 cases and 3204
      controls, was to precisely estimate the risk of VTE in patients bearing both
      mutations (double heterozygotes). Odds ratios for VTE were 4.9 (95% CI; 4.1-5.9)
      for the factor V Leiden and 3.8 (3.0-4.9) for the factor II G20210A mutation.
      Fifty-one cases (2.2%) and none of the controls were double heterozygotes. The
      odds ratio for venous thrombosis in double heterozygotes was 20.0 (11.1-36.1).
      Twelve percent of patients heterozygous for factor V Leiden were also
      heterozygous for factor II G20210A and conversely 23% of patients heterozygous
      for factor II G20210A were also heterozygous for factor V Leiden. Furthermore, in
      this large population we analyzed the effect of oral contraceptive (OC) in women
      carrying one of these mutations. Odds ratio for VTE associated with OC was 2.29
      (1.72-3.04). In factor V Leiden carriers using OC, the odds ratio for VTE was
      10.25 (5.69-1 8.45). The odds ratio of the association of factor II mutation and
      OC use was 7.14 (3.39-15.04). Finally, we also confirmed that the frequency of
      factor V Leiden was lower in patients with pulmonary embolism than in patients
      with deep vein thrombosis without PE (odds ratio 0.69). Conversely, factor II
      G20210A mutation was equally balanced in both patient groups.

PMID- 11583313
TI  - Incidence, natural history and risk factors of deep vein thrombosis in elective
      knee arthroscopy.
AB  - AIMS: to determine the incidence, anatomical distribution and extent of deep vein
      thrombosis (DVT) in limbs undergoing elective unilateral knee arthroscopy without
      active prophylaxis, to evaluate its effect on venous function following early
      diagnosis, and to quantify the impact of risk factors on its incidence. METHODS:
      102 consecutive patients undergoing unilateral knee arthroscopy without
      prophylaxis were studied. A history was obtained with emphasis on the risk
      factors for thromboembolism, and physical examination and colour duplex were
      performed prior to and within a week after surgery. Patients who developed calf
      DVT were given aspirin (150 mg) and compression stockings; those with proximal
      DVT were admitted for anticoagulation (heparin followed by warfarin). Follow-up
      (mean 118 [range 84-168] days) entailed weekly physical and duplex examinations
      during the first month and monthly thereafter. RESULTS: 8 patients developed calf
      DVT in the operated leg (incidence 7.84% [95% CI: 2.7%-13.2%]); thrombosis was
      asymptomatic in 4 of those (50%), caused calf tenderness in 4 (50%) and a
      positive Homan's sign in one (12.5%). DVT occurred in the following veins:
      peroneal 4 subjects (50%), soleal 4 (50%), gastrocnemial 2 (25%) and tibial 2
      (25%). Propagation of a calf DVT to the popliteal vein was identified in 1
      patient (12.5%). After a median period of 118 days, total clot lysis was found in
      50% of DVTs. with partial thrombus resorption in the rest; reflux in the
      thrombosed veins was present in 75% of limbs with DVT. 43% of patients had 1 risk
      factor for DVT and 20% had > or = 2. The incidence of DVT was higher amongst
      those with two or more risk factors for thromboembolism (p <.05) or those with
      previous thrombosis alone (p <.005). Symptoms or signs of pulmonary embolism were
      not documented. CONCLUSIONS: Elective unilateral knee arthroscopy performed
      without prophylaxis is complicated by ipsilateral calf DVT in 7.8% (95% CI: 2.7%
      13.2%) of cases. The risk is higher in the presence of previous thrombosis
      (relative risk: 8.2) and two or more risk factors for DVT (relative risk: 2.94).
      Thrombosis may propagate to the proximal veins, despite early diagnosis. 50% of
      calf clots totally lyse in 4 months, yet reflux develops in at least 75% of limbs
      with DVT. Further studies to determine optimal prophylaxis are warranted.

PMID- 11583314
TI  - Fibrin D-dimer, markers of coagulation activation and the risk of major ischaemic
      heart disease in the caerphilly study.
AB  - We have previously reported that plasma fibrin D-dimer (a marker of turnover of
      cross-linked fibrin) showed a strong and independent association with incident
      ischaemic heart disease (IHD) in the Caerphilly Study cohort of 1,998 men aged 49
      65. To establish the specificity of this finding, we assayed plasma samples from
      this cohort with a more specific assay for fibrin D-dimer: this showed an
      association with incident IHD which was at least as strong and independent as
      that for the original assay (odds ratio, OR for top fifth compared to bottom
      fifth 3.79; 95% CI 1.77-8.10; p < 0.0001). To establish potential causes of the
      increased fibrin turnover, we also assayed several potential markers of
      coagulation activation or thrombotic tendency (prothrombin fragment F1+2,
      thrombin-antithrombin complexes, factor VIIc, activated partial thromboplastin
      time [APTT] and activated protein C resistance): none of these variables were
      associated with incident IHD in this cohort. We suggest that further studies are
      required to establish the causes of increased cross-linked fibrin turnover, which
      is associated with incident IHD in the general population when measured by a
      specific assay.

PMID- 11583315
TI  - Disseminated intravascular coagulation in solid tumors: clinical and pathologic
      study.
AB  - Disseminated intravascular coagulation (DIC) is a well known hemostatic
      complication of solid tumors. We evaluated the occurrence of DIC in 1117 patients
      with solid tumors. Of these patients, 76 (6.8%) were diagnosed with DIC. There
      were a total of 145 bleeding and clotting episodes reported in the 76 patients.
      Thrombocytopenia, hypofibrinogemia, elevated D-dimer and fibrinogen degradation
      products were the most common coagulation abnormalities encountered in patients
      with DIC. In multivariate analysis, older age (p = .0001), male gender (p =
      .009), advanced malignancies (p = .027), breast cancer (p = .038) and the
      presence of necrosis in the tumor specimen (p = .004), emerged as independent
      factors significantly related to the occurrence of DIC in patients with solid
      tumors. Of the 76 patients, 25 (33%) achieved response to treatment of DIC as
      defined in the study. Patients with early stage and advanced malignancies who
      developed DIC had inferior survival when compared with their counterparts without
      DIC (p = .039 and p = .005, respectively). Taken together, this study indicates
      that certain clinical and laboratory features are more common in patients with
      solid tumors who developed DIC. The occurrence of DIC appears to have an
      independent effect on survival of patients with cancer. Cooperative studies are
      encouraged to better address the usefulness and optimal prophylactic heparin
      regimen in patients at risk for DIC.

PMID- 11583316
TI  - Platelet activation and platelet-erythrocyte aggregates in end-stage renal
      disease patients on hemodialysis.
AB  - Activated platelets may engage in dynamic interplay with other blood cells. We
      examined the evidence for platelet activation and the formation of platelet
      erythrocyte aggregates in chronic hemodialysis patients. Circulating activated
      platelets (P-selectin/CD63-positive platelets) were higher than normal controls
      (p < 0.001) and further increased during hemodialysis sessions, the increase
      being higher when patients were dialyzed with cellulosic than with synthetic
      membranes. We found direct evidence of uremic platelet-erythrocyte adherence in
      vitro and increased levels of circulating platelet-erythrocyte aggregates in
      dialysis patients, which represents a new observation in uremia. Platelet
      erythrocyte aggregates were subject to further increase during hemodialysis, and
      again higher levels were found with cellulosic than synthetic membranes. This
      phenomenon was reproduced in vitro by both ADP and PAF, but not by either
      complement factor C3a or by heparin concentrations corresponding to those used
      for clinical hemodialysis. We conclude that platelet-erythrocyte aggregates occur
      in hemodialysis patients probably owing to a primary platelet activation
      mechanism.

PMID- 11583317
TI  - Assembly of high molecular weight kininogen and activation of prekallikrein on
      cell matrix.
AB  - Investigations determined if extracellular matrix of endothelial cells (EC) is a
      platform for HK assembly and PK activation. In buffers containing bovine serum
      albumin, biotin-HK binding to ECV304 cells or their matrix requires > or = 50
      microM added Zn2+. Ortho-phenanthroline or a HK domain 5 peptide blocks HK
      binding. Binding to umbilical vein EC or matrix, but not ECV304 cells or matrix,
      is mediated by cytokeratin 1. Biotin-HK binds to ECV304 cells or matrix with a Kd
      of 15.8 or 9.0 nM and a Bmax of 2.6 x 10(7) or 2.4 x 10(7) sites/cell,
      respectively. PK activation on ECV304 cells or matrix is blocked by antipain or
      SBTI and corn trypsin inhibitor partially inhibits kallikrein formation. PK
      activation occurs on ECV304 cells or matrix prepared without serum or in human
      factor XII deficient serum, indicating that the PK activator is not factor XIIa.
      EC matrix promotes plasminogen activation after the assembly of HK, PK and pro
      urokinase. These studies indicate that matrix of various EC has the ability to
      assemble HK allowing for PK activation and subsequent activities.

PMID- 11583318
TI  - Ser968Thr mutation within the A3 domain of von Willebrand factor (VWF) in two
      related patients leads to a defective binding of VWF to collagen.
AB  - We report the identification of a new mutation of von Willebrand Factor (VWF)
      gene within exon 30 occurring in two related patients (mother and daughter) with
      a hemorrhagic syndrome. A T-->A transvertion at nucleotide 5441 was found
      changing the serine 968 to threonine of the mature VWF subunit (S1731T of the
      preproVWF). The Ser968Thr mutation is located within the VWF A3 domain which
      interacts with type I and III collagens. Both patients were found to be
      heterozygous for the mutation. The propositus (daughter) exhibited a slightly
      prolonged bleeding time, levels of VWF:Ag and VWF:RCo at the lower limit of
      normal, contrasting with normal levels of VIII:C. Her mother exhibited borderline
      bleeding time and moderately decreased levels of VWF and VIII:C. In both patients
      multimeric structure of VWF and ristocetin- as well as botrocetin-induced binding
      of VWF to GPIb were normal; however both patients repeatedly showed decreased
      binding of VWF to collagen. The Ser968Thr substitution was reproduced by site
      directed mutagenesis on the full-length cDNA of VWF. The mutated recombinant VWF
      (rVWF), T968rVWF, and the hybrid S/T968rVWF were transiently expressed by COS-7
      cells. Both rVWF exhibited normal multimeric pattern and normal ristocetin- as
      well as botrocetin-induced binding to GPIb. T968rVWF showed significantly
      decreased binding to collagen while the hybrid S/T968rVWF bound to collagen in a
      similar way to that of the patients' plasma VWF. Thus, our data demonstrate that
      the Ser968Thr mutation of the VWF A3 domain is clearly responsible for the
      abnormal binding of VWF to collagen observed in both patients. The Ser968Thr
      substitution of the VWF is the first mutation identified in two patients leading
      to a decreased affinity of VWF for collagen and a normal multimeric structure.

PMID- 11583319
TI  - Tissue distribution of factor VIII gene expression in vivo--a closer look.
AB  - Previous studies have shown that factor VIII (FVIII) is expressed by multiple
      tissues. However, little is known about its cellular origin or its level of
      expression in different organs. In the present study, we examined FVIII gene
      expression in different tissues on a quantitative basis. Most of the tissues,
      especially liver and kidney, expressed high levels of FVIII mRNA compared to
      their level of expression of other hemostatic proteins, including von Willebrand
      factor (VWF). This was unexpected since FVIII is a trace protein. In situ
      hybridization analysis confirmed that liver and kidney were rich in FVIII mRNA.
      In the liver, a clear hybridization signal was detected in cells lining the
      sinusoids. FVIII mRNA analysis of purified liver cells confirmed the expression
      of FVIII mRNA by sinusoidal endothelial cells and Kupffer cells. Low but
      significant levels of FVIII mRNA were also detected in the hepatocytes. VWF mRNA
      was not detectable in these cells. Similarly, immunohistochemical staining of
      liver tissue revealed that FVIII protein is primarily associated with sinusoidal
      cells. VWF protein was predominantly located in the endothelium of larger
      vessels. In the kidney, FVIII synthesis was localized to the glomeruli and to
      tubular epithelial cells. Taken together, these results suggest that besides
      hepatocytes, non-parenchymal cells (e.g. sinusoidal endothelial cells) contribute
      to FVIII synthesis. VWF synthesis is primarily confined to extra-hepatic tissues.

PMID- 11583320
TI  - Factor IX Denver, ASN 346-->ASP mutation resulting in a dysfunctional protein
      with defective factor VIIIa interaction.
AB  - Hemophilia B is a sex-linked recessive bleeding disorder characterized by the
      presence of either a decreased amount of normal factor IX (FIX) or the presence
      of a dysfunctional FIX. We have identified a unique mutation in a family with
      mild hemophilia B. DNA analysis of family members revealed a single base
      transition in the 8th exon of the FIX gene predicting an amino acid change of Asn
      346-->Asp in the catalytic domain. The FIX variant, named FIX Denver, was
      purified from proband plasma. Kinetic studies of factor X (FX) interactions with
      normal FIXa or FIXa Denver and phospholipid (PL) showed little difference in kcat
      but a significant difference when factor VIIIa (FVIIIa) was included in the
      reaction. Using kinetic assays to infer the Kd of FIXa for FVIIIa, normal FIXa
      had a Kd of 0.095 nM while that of FIXa Denver was 9.85 nM. The major defect
      caused by this point mutation is a marked decrease in the affinity of FIXa Denver
      for factor VIIIa.

PMID- 11583321
TI  - Hemostatic/fibrinolytic protein changes in C3H/HeN mice infected with Rickettsia
      conorii--a model for Rocky Mountain spotted fever.
AB  - Changes in plasma hemostatic and fibrinolytic proteins were determined during
      courses of a murine model of fatal and non-fatal Rocky Mountain spotted fever.
      C3H/HeN mice were infected with Rickettsia conorii and coagulation and
      histopathologic studies were performed at prescribed periods of time. A
      significant decrease in plasma factor VIII activity and rise in plasma factor V
      procoagulant activity correlated with a fatal infection. Factor VII levels were
      unchanged; factor XI levels dropped early in the course in the lethally infected
      animals, but returned to normal. Factor XII, high molecular weight kininogen, and
      prekallikrein levels were unchanged by the sublethal infection. Prekallikrein
      levels fell during the lethal infection. Antithrombin concentrations were
      decreased significantly in all animals, but plasma plasminogen levels did not
      change in either group of animals. Nonocclusive thrombi were microscopically
      observed rarely and only in animals surviving a sublethal infection. A fall in
      tissue plasminogen activator activity and a rise in plasminogen activator
      inhibitor activity highly correlated with a lethal outcome. Lethal infection with
      R. conorii is associated with primary endothelial cell injury resulting in
      decreased tissue plasminogen activator and increased plasminogen activator
      inhibitor.

PMID- 11583322
TI  - Impaired platelet function among platelet donors.
AB  - BACKGROUND: Platelet transfusions are effective for the prevention and treatment
      of bleeding in patients with disorders of platelet number and/or function. In
      recent years plateletpheresis concentrates have outnumbered pooled platelet
      concentrates, albeit with significant differences between nations. Thus, the
      platelet quality of individual donors has become increasingly important. The aim
      of this study was to gain an estimate for the prevalence of impaired platelet
      function among platelet donors. STUDY DESIGN AND METHODS: We determined the inter
      donor variability in platelet plug formation with a PFA-100 analyzer, the
      prevalence of impaired thromboxane formation, and effects of the density in
      alpha2 integrin polymorphism and density. RESULTS: (i) Collagen-epinephrine
      induced closure time (CEPI-CT) showed a great inter-subject variability in
      platelet donors and was higher than in healthy controls (p = 0.008). One-fifth of
      donors had abnormal CEPI-CT values and 11% exceeded >300 s (max measurable
      value). (ii) Decreased serum thromboxane B2 levels were found in 9% of all
      donors, compatible with surreptitious intake of cyclooxygenase inhibitors or with
      an aspirin-like defect. CEPI-CT correlated inversely with TxB2-levels in donors
      and controls. (iii) The density of the alpha2-integrin correlated negatively with
      CEPI-CT and CADP-CT values in controls, but was not responsible for the observed
      impaired platelet function in donors. (iv) Finally, the ABO blood group system
      modulates closure times. CONCLUSION: In sum, a large number of platelet donors
      present with prolonged closure times. Decreased thromboxane formation and
      frequent platelet donation partly account for this observation.

PMID- 11583323
TI  - The 33-kDa platelet alpha-granule membrane protein (GMP-33) is an N-terminal
      proteolytic fragment of thrombospondin.
AB  - GMP-33 is a platelet membrane associated protein that is recognised by RUU-SP
      1.77, an antibody raised against activated platelets. GMP-33 is predominantly
      associated with the membrane of platelet alpha-granules and it is translocated to
      the plasma membrane upon platelet activation (Metzelaar et al. Blood 1992; 79:
      372-9). In this study we have isolated the protein by immunoaffinity
      chromatography. The N-terminus was sequenced and was identical to the N-terminal
      sequence of human thrombospondin. The protein was N-glycosylated and bound to
      heparin as would be expected of the N-terminal part of thrombospondin. RUU-SP
      1.77 reacted only with reduced thrombospondin. Plasmin and trypsin digestion of
      thrombospondin yielded fragments of approximately the same size as GMP 33 that
      reacted with RUU-SP 1.77 after reduction. No evidence for alternative splicing
      was found. We postulate that GMP 33 is an N-terminal proteolytic fragment of
      thrombospondin that is membrane associated.

PMID- 11583324
TI  - Distinct domains of alphaIIbbeta3 support different aspects of outside-in signal
      transduction and platelet activation induced by LSARLAF, an alphaIIbbeta3
      interacting peptide.
AB  - The peptide LSARLAF causes alphaIIbeta3-dependent platelet activation exemplified
      by secretion, aggregation, spreading and adhesion on fibrinogen, and tyrosine
      phosphorylation. alphaIIIbeta3-dependent outside-in signal transduction induced
      by LSARLAF was investigated in variant thrombasthenic platelets which lack most
      of the cytoplasmic domain of the integrin beta3 subunit (alphaIIbbeta3 delta724).
      These studies revealed that only certain aspects of this alphaIIbbeta3-dependent
      outside-in signaling were affected by the beta3 truncation. Specifically,
      alphaIIbbeta3 delta724 supported LSARLAF-induced platelet aggregation,
      agglutination and secretion, but failed to trigger cytoskeletal reorganization
      and platelet spreading on fibrinogen, despite the fact that PMA-induced non
      alphaIIbbeta3 mediated signaling caused spreading of these platelets on
      fibrinogen. Thus, distinct domains of alphaIIbbeta3 are required to support
      different aspects of LSARLAF-induced platelet activation. Furthermore, these
      studies suggest that not all alphaIIbbeta3-dependent platelet responses require
      an intact beta3 cytoplasmic tail.

PMID- 11583325
TI  - A barbourin-albumin fusion protein that is slowly cleared in vivo retains the
      ability to inhibit platelet aggregation in vitro.
AB  - Barbourin is a 73 amino acid venom protein that inhibits platelet aggregation.
      Recombinant barbourin (BARH6), rabbit serum albumin (RSAH6), and a barbourin-RSA
      fusion protein (barbourin-linker-albumin; BLAH6) were secreted from Pichia
      pastoris yeast, and purified by nickel-chelate affinity chromatography via their
      C-terminal hexahistidine (H6) tags. BARH6 and BLAH6 did not differ in their IC50s
      for inhibition of platelet aggregation using either human platelets stimulated
      with thrombin or ADP, or rabbit platelets stimulated with ADP. BARH6 and BLAH6
      were also effective in inhibiting platelet aggregation in whole blood, and formed
      complexes with platelet integrin alphaIIbbeta3. The terminal catabolic half-life
      of BLAH6 approached that of RSAH6 [3.4 +/- 0.2 versus 4.0 +/- 0.1 days (n = 4 +/-
      SD)], but was substantially increased relative to that of BARH6 [0.15 +/- 0.03
      days (n = 3 +/- SD)]. Our results suggest that fusion to albumin slows the
      clearance of barbourin in vivo, while preserving its ability to inhibit platelet
      aggregation.

PMID- 11583326
TI  - Selective and sustained inhibition of surface-bound thrombin activity by
      intimatan/heparin cofactor II and its relevance to assessing systemic
      anticoagulation in vivo, ex vivo and in vitro.
AB  - We compare the relative activities of surface-bound and fluid-phase thrombin and
      their inhibition by heparin and Intimatan, a novel heparin cofactor II (HCII)
      agonist. In vitro, we compared the observed amidolytic activities of fluid-phase
      and surface-bound thrombin with the expected activities based upon 125I-specific
      activity. In vivo, we compared the inhibitory effects of heparin and Intimatan on
      thrombin activity bound to injured vessel walls. In vitro, the correlations
      between observed and expected activities of fluid-phase and surface-bound
      thrombin, were: r = 0.9974, p < 0.001; and r = 0.9678, p < 0.001; respectively.
      In vivo, injured vessel wall surface-bound thrombin activity persisted for > 24
      h. This activity was not inhibited by heparin, but was inhibited by Intimatan, p
      < 0.001. We conclude that surface-bound thrombin is as active as fluid-phase
      thrombin and remains protected from inhibition by heparin, thereby contributing
      to vessel wall thrombogenicity following injury. In contrast, surface-bound
      thrombin is inhibited by Intimatan, thereby effectively decreasing vessel wall
      thrombogenicity following injury in vivo.

PMID- 11583328
TI  - Plasmin proteolysis of endothelial cell and vessel wall associated tissue factor
      pathway inhibitor.
AB  - Plasmin is an important protease that mediates clot fibrinolysis and vessel wall
      extracellular matrix proteolysis. Recently, in vitro studies have suggested that
      plasmin can cleave and inactivate recombinant TFPI, a major inhibitor of TF
      mediated coagulation. We hypothesized that such an interaction may occur in
      vascular cells expressing TFPI, or in the vessel wall, with implications for
      thrombolysis. In a series of experiments, we examined the effects of plasmin on
      cell surface and extracellular matrix (ECM) associated TFPI in endothelial cells
      (EC) in culture and on EC and smooth muscle cells (SMC) in the vessel wall.
      Plasmin (0.2 microM) decreased cell surface and matrix associated TFPI activity
      in cultured endothelial cells by 77 +/- 5% and 69 +/- 6% respectively (p < 0.01).
      Plasminogen, the proenzyme form of plasmin had no such effect on cell surface
      TFPI or matrix TFPI. Cell surface TFPI antigen measured by fluorescence activated
      cell sorter (FACS) was also significantly reduced by plasmin. Proteolysis of
      conditioned medium TFPI was suggested by loss of a approximately 45kD TFPI on
      Western Blot analysis following plasmin treatment. Plasmin also proteolysed a
      approximately 45kD TFPI protein in the intact ECM of EC, an effect which was
      inhibited by preincubation with aprotinin, a plasmin inhibitor. Incubation of
      similar concentrations of plasmin, with homogenates of normal vessel decreased a
      approximately 45kD TFPI immunoreactive band on Western blot analysis. Plasmin
      also decreased surface TFPI activity on frozen sections of normal vessel as
      measured by an amidolytic assay. Finally, plasmin treatment of atherosclerotic
      plaque sections caused complete removal of TFPI immunoreactivity associated with
      luminal EC and intimal SMC, when compared to control treated plaque (n = 3).
      Together these data suggest that plasmin proteolyses the majority of EC
      associated (surface and matrix) TFPI and may remove TFPI from the luminal surface
      and intima of the vessel wall. TFPI proteolysis in cultured EC was associated
      with significant reduction in TFPI anticoagulant activity. These data provide
      evidence that plasmin degradation of TFPI occurs in vascular cells and in the
      vessel wall and may have implications for re-thrombosis following thrombolysis in
      vivo.

PMID- 11583327
TI  - Adenovirus-mediated expression of a truncated PDGFbeta receptor inhibits
      thrombosis and neointima formation in an avian arterial injury model.
AB  - Platelet-derived growth factor (PDGF) is a major mediator of neointima formation
      after arterial injury. We constructed a recombinant adenovirus, Ad/PDGFtr, that
      expresses the soluble extracellular domain of the murine PDGFbeta receptor
      (PDGFtr). The expressed PDGFtr was appropriately glycosylated and secreted by
      chicken vascular smooth muscle cells (SMCs) in vitro. The expressed PDGFtr
      inhibited human PDGF-BB induced receptor autophosphorylation, and also inhibited
      PDGF-BB induced cell proliferation without affecting PDGF-AA induced mitogenesis.
      In vivo transduction of balloon-injured rooster femoral arteries with Ad/PDGFtr
      resulted in expression and secretion of the glycosylated PDGFtr. The expressed
      PDGFtr significantly inhibited neointima formation compared with controls.
      Neointima-associated thrombus was significantly reduced in Ad/PDGFtr transduced
      arteries compared with controls. Thus, in addition to impacting on SMC
      proliferation and migration, PDGF-BB plays a role in thrombus formation in
      response to arterial injury. Growth factor inhibition by localized gene delivery
      constitutes a powerful approach to intervene in the molecular pathways involved
      in vascular disease.

PMID- 11583329
TI  - Pregnancy-related recurrent events in thrombophilic women with previous venous
      thromboembolism.

PMID- 11583330
TI  - Simvastain affects TAFI and thrombomodulin in CAPD patients.

PMID- 11583331
TI  - Congenital deficiency of vitamin K-dependent coagulation factors--a vitamin-K
      dependency state?

PMID- 11583332
TI  - The risk of overdiagnosis of antiphospholipid antibody syndrome.

PMID- 11583333
TI  - Imbalance towards Th2-type response in patients with definite primary
      antiphospholipid syndrome.

PMID- 11583334
TI  - Nature of the fibrinogen Aalpha gene TaqI polymorphism.

PMID- 11583335
TI  - Coronary stent thrombosis: insights from the porcine coronary stent model.

PMID- 11583336
TI  - Reply to rebuttal: Gene variants of the cytochrome P450 CYP2C9 affect oral
      anticoagulation with warfarin.

PMID- 11583337
TI  - Adrenal incidentalomas: surgical treatment in 28 patients and update of the
      literature.
AB  - INTRODUCTION: Adrenal masses discovered by imaging techniques for reasons
      unrelated to adrenal diseases are called adrenal incidentalomas (Al). The aim of
      this study was to find out the clinical outcome of 28 patients operated for
      incidentally discovered adrenal mass and to update the literature concerning this
      topic. PATIENTS AND METHODS: From September 1976 to December 1999 we operated on
      28 patients for adrenal incidentaloma. Adrenal masses were unilateral in 25 cases
      and bilateral in 5. Average age was 57 years (range 10-73). Hormonal study was
      performed in all patients. All patients underwent adrenalectomy by the
      transabdominal subcostal approach. RESULTS: Histopathology assessed the adrenal
      masses as primary in 19 patients and secondary in 9. 24-hour urinary
      vanillylmandelic acid (VMA) excretion was elevated in 2 patients. Adrenal
      insufficiency was detected in 1 case. Average tumor diameter resulted 5.8 cm
      (range 2-17). Histopathologic features of primary adrenal masses included
      pheochromocytoma in 5 cases, cysts in 4, myelolipomas in 3. nodular hyperplasia
      in 2, tuberculous mass in 1, cortical adenoma in 1, extra-bone marrow hemopoiesis
      in 1, cortical carcinoma in 1 and neuroendocrine tumor of the adrenal medulla in
      1. The 9 adrenal metastasis resulted by renal cell carcinoma in 7 patients,
      urothelial carcinoma of the upper urinary tract in I and primary renal lymphoma
      in 1. Average follow-up was 68 months (range 6-246). Patients alive were 18
      (64%), deal 10 (36%). Of the 19 patients with primary adrenal tumors 16 (84%)
      were alive and disease free and 3 (16%) died (I for disease and 2 for reasons
      unrelated to the primary tumor). Of the 9 patients with adrenal metastasis 2
      (22%) were alive (I disease free and I with progression of the disease) and 7
      (78%) died for disease. Replacement therapy for adrenocortical hormones was given
      5 patients. CONCLUSIONS: Management of Al need CT or MRI and hormonal
      investigation in order to detect malignancy and subclinical hypersecretory
      syndromes. Subclinical functional adrenal masses, single adrenal metastasis and
      primary nonhypersecretory adrenal tumors sized 4 cm are treated by surgery. A
      close morpho-functional follow-up is indicated for primary adrenal incidentalomas
      when nonhypersecretory and smaller than 4 cm.

PMID- 11583339
TI  - Correlation between renal blood flow and intrarenal Doppler measurements in
      canine autotransplanted kidney.
AB  - For proper interpretation of the changes in intrarenal Doppler ultrasound
      measurements, we evaluated the direct correlation between total renal blood flow
      and intrarenal Doppler parameters. Under progressive constriction of the renal
      artery in canine autotransplanted kidneys. we simultaneously measured blood flow
      at the main renal artery and Doppler parameters at the segmental artery. The
      changes in total renal blood flow were well correlated to changes in peak
      systolic velocity, end diastolic velocity and resistive index (RI) of the
      segmental artery (r = 0.964, 0.960 and 0.486, respectively). The acute reduction
      of total renal blood flow produces a linear decrease in Doppler parameters at
      intrarenal arteries. These results should be helpful for better understanding the
      changes in renal hemodynamics in various pathologic conditions as well as those
      induced by various vasoactive agents including angiotensin converting enzyme
      inhibitor.

PMID- 11583338
TI  - The role of ultrasonography in the detection of adrenal masses: comparison with
      computed tomography and magnetic resonance imaging.
AB  - To compare detection rates of adrenal tumors by ultrasonography, computed
      tomography and magnetic resonance image, we studied 61 patients with adrenal
      tumor, who underwent adrenalectomy. In 45 (73.8%) of the 61 patients. adrenal
      tumor was detected by ultrasonography. However, computed tomography and magnetic
      resonance imaging could detect all adrenal tumors. All adrenal tumors measuring
      more than 3.0 cm in diameter were detected by ultrasonography, computed
      tomography and magnetic resonance image. When adrenal tumors were smaller than
      3.0 cm. however, ultrasonography, computed tomography and magnetic resonance
      imaging correctly found adrenal tumors in 30 (65.2%) and 46 (100.0%) of 46
      patients and 30 (100.0%) of 30 patients, respectively. These facts suggest that
      ultrasonography seems to be an effective diagnostic procedure for the prevention
      of overlooking adrenal tumors larger than 3.0 cm.

PMID- 11583340
TI  - Hormonal and hemodynamic changes during percutaneous nephrolithotomy.
AB  - The aim of this study was to investigate the hormonal and hemodynamic changes
      during percutaneous nephrolithotomy (PCNL) procedure. Twenty-one patients between
      15-65 years of age were included in the study. Invasive blood pressure and heart
      rate were monitored during PCNL. Serum sodium, potassium, BUN and creatinine
      levels were measured before and after the operation. Sodium and potassium levels
      were also measured during the operation. Arterial blood gases, renin, aldosterone
      and adrenocorticotrophic hormone (ACTH) levels were measured before and during
      irrigation. The mean systolic and diastolic blood pressure levels were
      significantly higher (p < 0.05) during PCNL compared to post-procedure levels
      while heart rate remained constant. Serum sodium, potassium bicarbonate and base
      excess levels were decreased during the operation compared to the baseline levels
      (p < 0.001). BUN and creatinine levels remained unchanged during the study (p >
      0.05). In conclusion, a tendency to hyponatremia and metabolic acidosis developed
      in addition to significant increases in renin, aldosterone and ACTH levels during
      PCNL procedures. These changes may be due to the invasive nature of the
      intervention to the kidney and the continuous irrigation of this vital organ.
      This should be taken into consideration during PCNL. More detailed studies with
      larger groups are needed for more precise comments on this topic.

PMID- 11583342
TI  - Long-term results after percutaneous minimally invasive procedure treatment of
      symptomatic simple renal cysts.
AB  - OBJECTIVE: To assess the effectiveness and long-term results of two repeated
      ethanol injections in the treatment of symptomatic renal cysts. METHODS: Sixty
      eight patients 47 to 75 years old with 77 large (6.3-14.8 cm; mean 8.62 cm)
      symptomatic cysts were included in this study. Of the 68 patients, in 4 cases
      there were renal cysts associated with renal calculi. An 8FR Pigtail catheter was
      inserted into the cyst under ultrasound guidance followed by aspiration of cystic
      fluid. Two repeated ethanol 95% injections were performed every 24 hours.
      Patients were followed-up by ultrasonography for a period of 12-48 months (mean
      30). RESULTS: In two patients the cyst puncture was not feasible because of poor
      visualization of puncture site while in one patient there was communication of
      cystic cavity with the pelvocaliceal system. In these patients surgical resection
      of cysts was performed. Complete and partial regression rates were 57/68 (83.82%)
      and 8/68 (11.76%) respectively. In four patients with renal stones and renal
      cysts, extracorporeal shock wave lithotripsy (ESWL) was successfully executed I
      month after sclerotherapy. CONCLUSION: Our results suggest that percutaneous
      aspiration followed by two repeated ethanol injections is highly effective on
      reducing recurrence of simple renal cysts.

PMID- 11583341
TI  - Urine cytology in patients with urinary tract calculosis.
AB  - Urinary cytological examination was performed on 375 patients suffering from
      urolithiasis at the Department of Urology. University School of Medical Sciences,
      Bydgoszcz between 01.01.1991 and 31.12.1992. 189 were female (mean age: 47.5
      years), 186 were male (mean age: 53.5 years). We found dysplastic cells in
      urinary sediments in 25.3% of patients before therapy and in 5.3% of patients
      after conservative or traditional operation and interventional therapy (ESWL.
      PCNL). Degenerated cells were found in 72% of patients before therapy and in
      30.4% after therapy only. In our group neoplasmatical cells were not found.
      Inflammatory background was found in 44.5% before and in 21.9% after therapy,
      pyuria in 19.7% and 0.8% respectively. In urinary sediments we found concrements
      in 24% of patients before and 7.7% after therapy. However, 20 (51.3%) of 39
      patients after interventional therapy (ESWL, PCNL) had concrements in urinary
      sediments. In conclusion, no abnormality was seen in 85.1% before therapy and in
      31.2% after therapy. The significance of cytological examination in management of
      calculous diseases was discussed.

PMID- 11583343
TI  - ESWL in the treatment of stone in child with horseshoe kidney.
AB  - We report a case of struvite calculi in the child with horseshoe kidney treated
      by extracorporeal shock wave lithotripsy (ESWL). Complete stone clearance was
      obtained after 3 sessions using Siemens Lithostar Lithotriptor.

PMID- 11583344
TI  - The laparoscopic stylet.
AB  - A new instrument, laparoscopic stylet, developed for the laparoscopic extraction
      of the ureteral and renal pelvis calculi is described. The laparoscopic stylet is
      made of chromium nickel as a modification of the classical stylet. Until now,
      this instrument has been used in 11 retroperitoneoscopic ureterolithotomy
      operation and found to be quite useful for the mobilisation and extraction of the
      calculi from the ureters, suggesting its probable use also in the laparoscopic
      pyelolithotomy procedures.

PMID- 11583345
TI  - Calyceal fornix rupture during cystography.
AB  - We report the first case of calyceal fornix rupture due to cystography in the
      literature. We recommend that instillation of all the contrast material should be
      attentively traced by the fluoroscope during cystography.

PMID- 11583346
TI  - Giant pseudoaneurysm of posterior division of renal artery: a rare complication
      of pyelolithotomy.
AB  - Giant renal artery pseudoaneurysm after pyelolithotomy is an uncommon but
      important disorder. A case of giant pseudoaneurysm arising from the posterior
      division of right renal artery following pyelolithotomy is presented. The patient
      presented with a flank mass six months after pyelolithotomy. CT-scan as well as
      selective renal angiography revealed a giant pseudoaneurysm arising from the
      posterior division of renal artery. Nephrectomy was necessitated as selective
      embolization was not possible due to its extraordinarily large size.

PMID- 11583347
TI  - Repair of bilateral complete ureteral ligation that occurred during hysterectomy.

PMID- 11583348
TI  - Trans-uretero-ureterostomy with a blind-ending ureteral duplication.

PMID- 11583349
TI  - Urologic manifestations of multiple sclerosis: proposed treatment algorithms.
AB  - PURPOSE: A detailed clinical management of the urological manifestations of
      multiple sclerosis (MS) is presented as it is practiced in our department, and
      therapeutic algorithms are constructed. MATERIALS AND METHODS: One hundred and
      ten patients were consecutively and prospectively studied with a clinical
      syndrome of MS. ranging in age from 32 to 65 years of age. Clinical diagnosis of
      the voiding dysfunction associated with MS was classified as a malfunction
      causing either problems of bladder evacuation, or storage, or a combination of
      both. RESULTS: All patients were initially managed in a conservative way avoiding
      surgical procedures and following primarily pharmacologic treatment, because of
      the quite common reversibility of MS. The detailed management of the related
      voiding dysfunction is given by the proposed algorithms. CONCLUSIONS: Our purpose
      was to present the algorithms that can help the practicing physician to come to
      reasonable conclusions as to therapeutical choices directed to specific
      pathophysiologic characteristics of voiding dysfunction related to MS.

PMID- 11583350
TI  - Vesicourethral dysfunction associated with multiple sclerosis: correlations among
      response, most prevailing clinical status and grade of the disease.
AB  - PURPOSE: In the present study we have performed a correlation of the most
      prevailing clinical conditions of multiple sclerosis (MS) with overall drug
      response and the grade of the disease. MATERIALS AND METHODS: One hundred and ten
      patients were consecutively and prospectively studied with a clinical syndrome of
      MS, ranging in age from 32 to 65 years of age. In the present study we evaluated
      the patients with DESD (n = 35), detrusor hyperreflexia (n = 32), and/or low
      compliance (n = 8). The latter three conditions were considered as the most
      threatening, and thus a correlation with the drug response and the grade of the
      disease was attempted. RESULTS: All patients were initially managed in a
      conservative way avoiding surgical procedures and following primarily
      pharmacologic treatment, because of the quite common reversibility of MS. Our
      results suggest that there is no correlation between the prevailing clinical
      status and drug response (p = 0.06) or grade of the disease (p = 0.07). The only
      statistically significant correlation was seen between grade of the disease and
      overall drug response (p < 0.0001) CONCLUSIONS: Therapeutic responses were
      dependent upon the grade of the disease. The continuation of this study
      recruiting more patients into various subgroups of voiding dysfunction will
      further validate the statistical correlations among disease grade and therapeutic
      responses.

PMID- 11583351
TI  - Clinical management of the neurourological syndrome associated with multiple
      sclerosis and correlations to grade of the disease.
AB  - PURPOSE: In this study a detailed clinical management is presented as it is
      practiced in our department, and possible correlations between grade of the
      disease and therapeutic responses are examined. MATERIALS AND METHODS: One
      hundred and ten patients were consecutively and prospectively studied with a
      clinical syndrome of MS, ranging in age from 32 to 65 years of age. Clinical
      diagnosis of the voiding dysfunction associated with MS was classified as a
      malfunction causing either problems of bladder evacuation, or storage, or a
      combination of both. Therapeutic responses of the voiding dysfunction were
      correlated with grade of the disease. Mean follow up period was 54 months.
      RESULTS: All patients were initially managed in a conservative way avoiding
      surgical procedures and following primarily pharmacologic treatment, because of
      the quite common reversibility of MS. A possible correlation of response to
      treatment according to grade of the disease was studied. There was significant
      difference in the response to drug treatment among patients of different grades
      favoring grade 1 patients with both storage and evacuation voiding dysfunction.
      CONCLUSIONS: Our suggested treatment has secured the conversion of a high
      pressure into a low pressure vesicourethral system, thus obviating possible risk
      factors for the upper urinary tract and the bladder itself. Therapeutic responses
      were dependent upon the grade of the disease.

PMID- 11583352
TI  - Intravesical oxybutynin affects bladder permeability.
AB  - To investigate the effects of intravesical application of oxybutynin chloride on
      bladder permeability we designed an animal model. Female Guinea pigs were given 3
      different test solutions: phosphate buffered saline (PBS), 50% acetone and 1.27 x
      10(-2) M oxybutynin chloride solution. Then 99mTc-DTPA 45 microCi in 2 ml normal
      saline was instilled into the bladder lumen in each animals and allowed to dwell
      for 30 minutes. At the end of exposure time, the net count data in each 1 ml
      serum sample were corrected for radioactive decay and converted to the total
      percentage of administered dose. 99mTc-DTPA absorption percentages of both
      acetone and oxybutynin groups were significantly higher than that of PBS group
      (mean 3.2 +/- 2.9% p < 0.001). Intravesical oxybutynin application increases
      bladder permeability 5 times compared with PBS administration. This observation
      can also explain how rapid absorption of oxybutynin through the bladder into the
      systemic circulation occurs.

PMID- 11583353
TI  - Urinary incontinence after pelvic trauma: a case report.
AB  - Stress and Urge urinary incontinence may develop after a pelvic trauma especially
      after pelvic bone fractures. Incontinence may persist even though any type of
      bladder neck suspension is performed if malunion occurs between fracture ends. In
      stress and urge urinary incontinence developed after pelvic trauma, patients
      should also be evaluated for malunion of fractures which may lead to bone spurs
      and during any type of bladder neck suspension these should also be removed.

PMID- 11583354
TI  - Evaluation of nuclear matrix protein 22 (NMP22) as a tumor marker in the
      detection of bladder cancer.
AB  - We prospectively evaluated the performance of urinary NMP22 test in the detection
      of transitional carcinoma (TCC) of the bladder. Urine samples were obtained from
      39 patients with known bladder cancer, 37 patients with primary hematuria. 18
      with benign urological conditions and 20 healthy subjects. Overall sensitivity
      and specificity of NMP22 with reference value of 10 U/ml was 72 and 73%,
      respectively. Sensitivity for pT1 and pT2 tumors was 83%, whereas that for pTa
      tumors was 55%. When the test was determined before and after transurethral
      resection (TUR) of bladder tumor, it was shown that the TUR effected the NMP22
      level. Urinary NMP22 was highly sensitive for high-risk bladder cancer. However,
      the sensitivity of the test is somewhat lower in low grade and stage tumors.
      Additionally, the effect of previous resection limits its value in the follow up
      of patients with superficial tumors. The larger series with longer follow up may
      lead us to determine the time to neglect the effect of TUR on NMP22 and the test
      kit should be upgraded by the manufacturer to exclude the false positive results
      due to inflammatory conditions.

PMID- 11583355
TI  - Ileal orthotopic neobladder in women: the first experiences from Turkey and our
      modifications.
AB  - The lower urinary tract reconstruction with an ileal neobladder in woman is not
      very often but has been recently introduced centers. We report 8 female patients
      with ileal orthotopic neobladders after cystectomy. PATIENTS AND METHODS: Between
      1995 to 1999, 7 female patients with organ confined invasive bladder cancer and 1
      female patient with severely contracted bladder secondary to tuberculosis were
      operated. While standard radical cystectomy was done in 7 patients with bladder
      cancer, only simple cystectomy was performed in patient with contracted bladder.
      Detubularized ileal W-neobladder with antirefluxive ureteroileal reimplantation
      were used as a procedure and reservoirs are connected to the proximal urethra in
      all patients. Cystoscopy and biopsy was done routinely in the bladder neck and
      there were no tumour and CIS in any patient. RESULTS: The mean age was 65.4 years
      (53-70) and the mean postoperative follow-up time was 31.8 months (6-48). There
      was no perioperative or early postoperative (first one month) mortality. Early
      postoperative complications included acute renal failure in I patient (12.5%),
      deep vein thrombosis in 1 patient (12.5%) and leakage from the pouch in 2
      patients (25%). In one patient (12.5%), ileo-pouchal fistula was seen in sixth
      month and reoperated. Although there was not hypercontinence. one patient (12.5%)
      had totally incontinence. All other patients had normal micturition and no
      residual urine. Urethral recurrence was not seen in this postoperative follow-up
      period but pelvic recurrence and then distant metastases were found in one case
      (12.5%). CONCLUSIONS: The results of ileal orthotopic neobladder after radical or
      simple cystectomy in appropriate female patients are satisfactory. But certainly,
      we need the more experiences and studies about this subject.

PMID- 11583356
TI  - Bladder cancer mortality in the Epirus district population (Greece).
AB  - OBJECTIVE: To describe the pattern of bladder cancer mortality in the Epirus
      district population (North-Western Greece) and to establish some relationships
      with cigarette smoking. PATIENTS AND METHODS: Mortality rates of bladder cancer
      in the Epirus district population were analysed according to the official data
      from the Department of Statistics of the University Hospital of Ioannina during
      the last decade (January 1990-January 2000). Age standardization of death rates
      was done by the direct method, using the world population as a standard. Fisher's
      test was used as a significance test for linear regression coefficient in time
      trend analysis of mortality. RESULTS: The average annual standardized mortality
      rates from bladder cancer during the study period were 5.23 per 100,000
      population (96% Confidence Interval--Cl 4.02-5.63) in males and 1.63 per 100,000
      population (96% Confidence Interval--CI 1.18-1.96) in females. Significantly
      increasing trends of the rates were observed in males (y = 2.421 + 0.231x; p <
      0.01), but not in females (y = 1.263 + 0.027x: p > 0.05). The greatest increase
      in age - specific rates in males was observed in the age group of 70 and more
      years (y = 25.602 + 3.673x; p < 0.01). In females, all age--specific rates except
      for the group 60-69 years showed significantly increasing tendency. The
      increasing tendency of bladder cancer mortality is followed by the rise of per
      capita cigarette consumption among the Epirus district population. CONCLUSION:
      Further studies are needed for the explanation of the irregularities in the age
      specific rates.

PMID- 11583357
TI  - Pilot study of the practical relevance of a one-step test for prostate-specific
      antigen in capillary blood to improve the acceptance rate in the early detection
      program of prostate carcinoma.
AB  - OBJECTIVE: Current studies have proven that early, organ-confined stages of
      prostate cancer can be diagnosed through screening based on PSA levels, thus
      reducing cancer mortality. Here we report about our experience using an
      innovative one-step test for PSA in capillary blood. METHODS: The incubation time
      for a 50 microl blood sample with the indicator strip is 12 minutes until the
      qualitative visual results (<4.0 ng/ml or > or = 4 ng/ml) appear. In cooperation
      with urologists and accompanied by an extensive information campaign, the one
      step test was made available free of charge to all men between the ages of 45 and
      75 in all 28 pharmacies of our city (100,000 inhabitants). RESULTS: The test's
      acceptance rate among the 2,119 participants between the ages of 45 and 75 years
      amounted to 13.0%. Fifteen percent of all the tests conducted showed a positive
      PSA result (> or = 4 ng/ml). Prostate carcinoma was histologically confirmed in
      14 (0.66%) of the men, nine times in the early stage (T2) and five times in the
      clinical stage (T3), corresponding to an incidence of circa 650 cases per 100,000
      men in the target age group. CONCLUSIONS: This newly developed PSA test system
      can enhance the acceptance rate and effectiveness of medical check-ups for
      prostate cancer, because it is easy-to-use, cost-effective and accurate
      (specificity 81.3%, sensitivity 91.1%). The test should be always conducted by an
      experienced physician or pharmacist. It is not a substitute for a regular
      physical examination (DRE, TRUS, biopsy...).

PMID- 11583358
TI  - Bone age in children with nocturnal enuresis.
AB  - It is widely believed that nocturnal enuresis is caused by a hereditary delay in
      maturation of the various organ systems. In this study, growth and bone age were
      investigated in enuretic children. There was a significant bone age lag in the
      enuretic group compared to the control subjects of similar age (8.15 +/- 1.56
      years vs 9.45 +/- 2.17 years, p < 0.05). It has been suggested that skeletal
      maturation also are retarded in nocturnal enuresis; and, it may be caused by the
      delayed maturation in regulatory functions of the central nervous system

PMID- 11583359
TI  - Analysis of heart rate variability in children with primary nocturnal enuresis.
AB  - Although nocturnal enuresis is probably the most common developmental disorder in
      children, the pathogenesis and management remain unclear. Autonomic dysfunction
      is one of the proposed mechanisms for nocturnal enuresis in children. The
      objective of current study was to evaluate autonomic nervous system functions in
      enuretic children. Twenty-four-hour ambulatory electrocardiographic recordings
      were obtained, and the time domain variables of HRV were calculated. The results
      of the present study suggest that sympathetic nervous system hyperactivity is
      present in enuretic children. This may explain why some enuretic children do not
      respond to anticholinergic medications. If these conflicting results are
      confirmed by large-scale clinical studies, Holter ECG examinations may be used
      for rational approaches in treatment of nocturnal enuresis.

PMID- 11583360
TI  - A rare foreign body on penis leading to incarceration.
AB  - Foreign body on penis is usually put himself or by his female partner by adults
      for sexual gratification and in children as an innocent childish play. We have
      managed a 10 years shepherd who put on a bark of tree with successful outcome
      which is not being reported in literature.

PMID- 11583361
TI  - The efficacy of sildenafil in different etiologies of erectile dysfunction.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy of sildenafil and
      success of treatment in particular etiological causes in erectile dysfunction
      lasting more than 3 months. MATERIAL AND METHODS: A total of 141 patients between
      27 and 78 years old without any cardiac compromise, despite controversial, which
      precludes sildenafil (Viagra) treatment, were included in this study. All
      patients had only International Index of Erectile Capacity Form (IIEF) for pre
      treatment evaluation and 50 mg sildenafil was started. Patients were assessed
      monthly for 6 months thereafter. Erectile capacity changes were questioned by
      IIEF on each follow-up and 100 mg sildenafil was given in patients without a
      response and monthly follow-up was scheduled. All patients had SMA-12, hormonal
      analyses and penile colour Doppler ultrasonography during the treatment course.
      The difference between IIEF score of each patient was displayed by Paired-t test
      and p-values less than 0.05 was applied as significant. RESULTS: The average
      beginning IIEF score of 141 patients was 11.80 +/- 0.47 [6-22], and increased to
      20.70 +/- 0.62 [6-30] after a month of 50 mg sildenafil treatment. The mean
      increase was 75.4% and found to be significant (p = 0.000, p < 0.05). The average
      IIEF scores were recorded as 22.57 +/- 0.69 after 3, and 22.12 +/- 0.24 after 6
      months. There was no difference between these values and 2nd month controls (P3
      month = 0.5675, P6 month = 0.6138, p > 0.05). A positive response was recorded in
      102 patients (72.3%) and 39 (27.7%) patients were unresponsive. Doubled doses of
      sildenafil (100 mg) was effective in additional 17 patients. After overall
      treatment, 119 (84.4%) patients had benefit from sildenafil. Penile Doppler
      ultrasonography displayed arterial insufficiency in 79 (56.03%), veno-occlusive
      dysfunction in 14 (9.93%), mixt vascular pathology in 14 (9.93%) patients. Normal
      ultrasonographic findings in 32 patients (22.7%) were classified as psychogenic
      dysfunction. Among the organic causes, sildenafil was found to be most effective
      in arterial insufficiency group. CONCLUSION: Sildenafil is a successful
      management modality in erectile dysfunction with minimal pre-treatment
      evaluation. As far as etiological causes concerned, sildenafil was found to be
      most effective in arterial insufficiency group and psychogenic group. The
      efficacy of sildenafil treatment has not been changed with the treatment time,
      since IIEF scores were stable during follow-up controls.

PMID- 11583362
TI  - Sildenafil (Viagra): is there an influence on psychological performance?
AB  - BACKGROUND: Sildenafil (Viagra) is a well-introduced medicine for erectile
      dysfunction; many studies about effects and side effects are published. Beside
      these aspects of treatment the influence of sildenafil on psychophysical
      performance is of interest. cGMP is one of the most important second messengers
      in the central nervous system (CNS), so even very small changes of the
      intracellular cGMP-level caused by phosphodiesterases inhibition may be relevant
      for CNS-function. We wanted to verify the hypothesis whether sildenfail
      influences human psychomotor performance, especially under the aspect of traffic
      safety, or not. METHODS: Designed as a pilot study we tested 6 male healthy
      volunteers using a test battery of 7 different psychophysical performances tests.
      Each individual did the test battery twice, once without drug and once after a
      single oral dose of 100-mg sildenafil. 3 persons did the first and 3 others did
      the second experiment under the influence of drug (UID). All results (37
      parameters) were analysed by t-test for paired samples using a confidence
      interval of 95%. RESULTS: Only two parameters of 2 different tests showed
      significant differences. In the simple choice reaction test (DR2) the mean
      reaction time got better in the group with sildenafil; in the multiple choice
      reaction test with stress induction (RST3) the amount of wrong answers indicated
      a weak influence of performance without statistical significance, six parameters
      (dominantly in the speed anticipation test (DEST)) represented an increase and
      one other (RST3 second part) showed a decrease UID. The uppermost parameters (76%
      of all items) stayed on equal levels for both groups. CONCLUSION: Sildenafil
      showed no important impairment of psychophysical performance, no strong
      improvement was found as well. With a look at the therapeutically indication of
      sildenafil the improvement in sexual activity may indicate no incapacity in
      traffic and other psychomotoric/psychophysical functions.

PMID- 11583363
TI  - Multilocular spermatocele: a case report.
AB  - We describe a case of a multilocular spermatocele. Ultrasound examination
      revealed several cystic spaces at the head of the left epididymis. Epididymal
      tumor could not be excluded, and therefore surgical exploration was performed.
      Histopathological examination of the specimen revealed a multilocular
      spermatocele arising from the rete testis. Most spermatoceles remain small and
      rarely present marked clinical problems. but they are occasionally large, and may
      simulate a solid tumor.

PMID- 11583364
TI  - Ureteric stone extraction with retrograde irrigations balloon catheter.

PMID- 11583365
TI  - DNA damage induced by lithotripter generated shock waves: short report.
AB  - The side effects of shock waves on biological tissues have been intensively
      investigated in past years. In contrast to the morphological studies, only a
      little information exists up to now about molecular effects of shock waves at the
      DNA level. To study the shock wave effects on DNA in water solution, 100, 500,
      1,000, 1,500 wave shocks, generated with a experimental lithotripter, were
      applied at 18 kV and 20 kV, corresponding to the positive pressure peaks of 16
      and 30 MPa and negative ones of 5 and 9 MPa. The DNA damage was evaluated in two
      "submarine" electrophoresis approaches. In the first - standard DNA
      electrophoresis - no DNA damage was detected, confirming previously described
      results. In the second electrophoresis, performed under changed conditions, sever
      double strand DNA damage was found. Our results strongly suggest that shock waves
      applied at the therapeutical level of energy may generate the double strand DNA
      damage.

PMID- 11583366
TI  - Efficacy and tolerability of drugs for treatment of benign prostatic hyperplasia.
AB  - It has long been recognised that neural factors are of considerable importance in
      lower urinary tract function. Whilst reduction in the bulk of the human prostate
      is feasible, experience on this therapeutic approach proved to be disappointing.
      Existing trial data with the agent finasteride are reviewed. A number of
      formulations derived from plant extracts have been advocated but their mechanism
      of action remain largely obscure and there is a dearth of placebo controlled
      information to support their efficacy. Experience over the last 10 years has
      demonstrated efficacy with the use of alpha adrenoceptor blockade in the
      management of BPH. Alpha adrenoceptor antagonists relax the prostatic smooth
      muscle by interrupting the sympathetic pathway at the receptor level. Recent
      developments in this field include the recognition that there are alpha I
      adrenoceptor subtypes. The functional adrenoceptor in the human prostate is
      predominantly the alpha IA - subtype. Of the alpha 1-adrenoceptor antagonists
      only tamsulosin discriminates between the alpha 1-adrenoceptor subtypes. Alpha 1
      blockers should be used in first-line medical therapy for BPH and 5-alpha
      reductase inhibitors reserved for those patients in whom alpha-blocker therapy
      fails. Alpha I-blockers such as doxazosin, tamsulosin, terazosin, alfuzosin are
      effective in the treatment of BPH both in younger and in older men. The drugs are
      well tolerated. The majority of side effects were classified as minor and mild.
      The most common complaints, as with other alpha-blockers, are dizziness, fatigue
      and headache, and these are often transient. In contrast, finasteride can lead to
      impotence, reduced libido. gynaecomastia or ejaculatory disorders. Men with small
      prostates may not be suitable candidates for finasteride therapy.

PMID- 11583367
TI  - Use of terazosine in patients with chronic pelvic pain syndrome and evaluation by
      prostatitis symptom score index.
AB  - PURPOSE: Chronic Pelvic Pain Syndromes (CPPS) affect an important percentage (5
      9%) of the patients in urology practice; however there has been no consensus as
      to how the treatment should be planned in these patients. The purpose of our
      study is to evaluate the effectiveness of terazosine in the treatment of CPPS
      patients. MATERIALS AND METHODS: In our outpatient department, between May 1997
      and October 1999, 91 patients were diagnosed as CPPS. These patients were first
      evaluated by Prostatitis Symptom Score Index (PSSI) and then randomized into two
      treatment groups. The first group received 2 mg/day terazosine (47 patients), and
      the others received placebo (42 patients). After three months of treatment, 69
      patients came back for the control visit (terazosine 39, placebo 30). They were
      reexamined by PSSI and their results were evaluated by Wilcoxon analysis.
      RESULTS: Before the treatment PSSI of the 39 patients who received terazosine
      were 9.61 +/- 1.61, after the treatment they were 6.25 +/- 1.60. For the placebo
      group, PSSI values before the treatment were 9.27 +/- 1.88 and after the
      treatment they were 8.81 +/- 2.66. In the terazosine group, the difference
      between the pretreatment and post treatment PSSI values was statistically
      significant (p = 0.0002). In the placebo group, on the other hand, this
      difference was statistically insignificant (p = 0.701)). After the treatment, the
      difference between the terazosine and placebo groups was also statistically
      significant (p = 0.001). In the terazosine group (as the recommendation was to
      take the medication at night) postural hypotension did not develop. CONCLUSION:
      Terazosine was effective for the treatment of CPPS. However it was concluded that
      three months of treatment was insufficient.

PMID- 11583368
TI  - Acute and chronic urinary tract infections caused by Chlamydia trachomatis.
AB  - Chlamydia trachomatis is one of the causes of acute and chronic urinary tract
      infections and acute or silent salpingitis. Chronic or recurrent female urinary
      or genital tract infections with Chlamydia trachomatis have been recognised as a
      significant factor in the development of acute or chronic renal interstitial
      inflammation or increased risk of ectopic pregnancy. In most cases Chlamydia
      trachomatis is sexually transmitted. Moreover, it is one of the most common
      sexually transmitted pathogens. The current estimate is that in the United States
      there occur 4.5 million new infections each year. We describe 3 cases of
      recurrent urinary tract infections due to Chlamydia trachomatis.

PMID- 11583369
TI  - Body mass index as a predictor of continued survival in older chronic dialysis
      patients.
AB  - OBJECTIVE: To investigate the contribution of body mass index (BMI) to mortality
      over 11 years of follow-up in a prevalent sample of dialysis patients aged 60+.
      DESIGN: Multivariate Cox proportional hazards regression analysis. SETTING:
      Multicenter stratified random sample of black and white older chronic dialysis
      patients in a southeastern state. SUBJECTS: 316 patients on hemodialysis (HD) and
      peritoneal dialysis (PD). MAIN OUTCOME MEASURE: Continued survival from baseline
      interview in 1988 to June 1999. RESULTS: Adjusting for age, primary diagnosis of
      diabetes, cardiovascular comorbidity, HD/PD therapy, and patient-reported
      functional impairment, the interaction of baseline BMI with race and gender was
      associated with older patients' risk of mortality. Black females, black males,
      and white males with higher BMI had a reduced risk of mortality, while no
      protective effect of higher BMI was found for white females. Patients with
      cardiovascular comorbidity and greater functional impairment at baseline had
      increased mortality risk. BMI was not significantly correlated with serum albumin
      or functional impairment. CONCLUSION: BMI, a simple anthropometric measure that
      provides a marker of nutritional status, interacts with race and gender to
      predict long-term survival in older dialysis patients. The association of
      survival with dialysis adequacy, nutritional indicators, and cardiovascular
      status in black and white dialysis patients is an important area of study.

PMID- 11583370
TI  - The relation between nutrition indices and age in patients on continuous
      ambulatory peritoneal dialysis receiving similar small solute clearances.
AB  - OBJECTIVE: To analyze the effect of age on nutrition indices in subjects on the
      same continuous ambulatory peritoneal dialysis (CAPD) schedule. METHODS: We
      analyzed 613 sets of clearance values and nutrition indices in 302 CAPD patients.
      Small solute clearances included urea clearance (Kt/Vurea) and creatinine
      clearance (Ccr). Nutrition indices included body mass index (BMI), serum albumin,
      urea and creatinine, 24-h urea nitrogen and creatinine excretion in urine plus
      dialysate, protein nitrogen appearance (PNA), PNA normalized by standard weight
      (nPNA), lean body mass (LBM) computed by creatinine kinetics, and LBM/Weight.
      CAPD subjects were classified in 4 age quartiles (Q): Group Q1, age 33.7 +/- 7.6
      years, N = 149; group Q2, age 49.5 +/- 3.8 years, N = 158; group Q3, age 61.5 +/-
      2.6 years, N = 154; and group Q4, age 72.1 +/- 5.4 years, N = 152. Group
      comparison was done by one-way ANOVA or chi-square. Predictors of low nutritional
      parameters were identified by logistic regression. Selected variables were
      compared by linear regression. RESULTS: Mean Kt/Vurea and Ccr were above the
      current adequacy standards and did not differ between the age quartiles. In
      contrast, older quartiles had, in general, lower nutrition indices than younger
      quartiles. However, the youngest quartile had the lowest BMI. By logistic
      regression, young age was a predictor of low BMI, while advanced age was a
      predictor of low creatinine and urea nitrogen excretion, low nPNA, and low
      LBM/Weight. The regressions of nPNA on Kt/Vurea differed between the age
      quartiles. By these regressions, the youngest quartile had higher nPNA values for
      the same Kt/Vurea than the oldest quartile in the clinically relevant range of
      Kt/Vurea and nPNA values. CONCLUSIONS: Nutrition indices are worse in older than
      in younger CAPD patients with the same small solute clearances. Nutrition of CAPD
      patients is adversely affected by age and requires special attention in the older
      age group.

PMID- 11583371
TI  - Hemodialysis vascular assessment by an ultrasound dilution method (transonic) in
      patients older than 65 years.
AB  - Malfunction of vascular access is one of the most frequent causes of morbidity
      and mortality in hemodialysis patients (HD). Early diagnosis makes possible the
      most frequent vascular access (VA) used in HD patients. The arteriovenous fistula
      (AVF), both autologous or heterologous, is the appropriate correction by an
      interventional radiologist or by surgery, before thrombosis appears. For this
      purpose, a follow-up of VA is mandatory. New technologies offer non-invasive
      methods for this purpose. In HD sessions ultrasound 'on line' and ultrasound
      dilution techniques permit us to monitor vascular access in HD patients. Also
      transonic technology has been validated for this purpose, although the
      limitations of its use among elderly patients is unknown. Using the Transonic
      HD01 monitor, we studied vascular access in 45 patients in HD older than 65
      years, and compared them with 47 patients who were younger than 65 years. The
      parameters analyzed were: effective flow Qt, recirculation, venous pressure and
      access flow. We found no significant differences between these parameters but in
      both groups found that the effective flow measure by Transonic was lower than
      that measured by a blood pump. Both groups contained patients who had no
      recirculation but had an access flow that was lower than expected. To rule out
      stenosis of VA in those patients, we performed an Eco Doppler confirming that all
      patients had stenosis. With this method, one can determines the access flow and
      thus predicts the possibility of future thrombosis. CONCLUSION: Our data confirm
      that one can evaluate VA in patients older than 65 years with Transonic HD01
      monitor, and also in patients younger than 65 years. Due to the special
      characteristics of the vessels in elderly patients, Transonic HD01 monitor is a
      good method by which to monitor VA in them.

PMID- 11583372
TI  - Plasma glutathione peroxidase activity in the elderly.
AB  - Schiavon et al. (1994) have reported that the measurement of plasma glutathione
      peroxidase activity (PGP) could provide an index of renal function. Its activity,
      which was depressed in patients with impaired renal function, correlated
      positively with creatinine clearance and negatively with serum creatinine. To
      evaluate the hypothesis that the plasma PGP activity may be used to assess renal
      function in elderly, we measured the plasma PGP and creatinine clearance (ClCr)
      in 65 active, community-dwelling elderly (range: 65-93 years; 47 women and 18
      men). We did not include persons with advanced renal failure in our study. PGP
      did not correlate with PCr and it was similar among patients with normal and with
      increased PCr (127.0 +/- 30.7 U/l and 119.7 +/- 21.6 U/l, respectively). A
      positive correlation was found between PGP and ClCr (r = 0.30; p < 0.01). Plasma
      PGP activity was lower in patients with a ClCr lower than 70 ml/min/1.73 m2 than
      in those who had a higher ClCr (113.0 +/- 25.8 U/l and 131.2 +/- 26.7 U/l, p <
      0.01). However, no correlation was found between ClCr and PGP in subjects with
      lower ClCr. PGP did not correlate with age but there was a correlation between
      ClCr and age (r = -0.24, p < 0.05). Our results suggest that plasma PGP activity
      is decreased in the patients with impaired renal function but this decrease does
      not correlate with age-dependent decline of kidney function.

PMID- 11583373
TI  - Geriatric nephrology units: the way of the future.
AB  - The emergence of the sub-speciality geriatric nephrology is an exciting
      development for the future. The main objectives should be to maximise patient
      independence and minimise deterioration and learn dependent behaviour in this
      population. To achieve these goals a holistic approach needs to be taken, to the
      patient, their environment and the efficacy of such units, and this can only be
      achieved using a multi-disciplinary team approach. In the creation of a geriatric
      nephrology unit it is important to identify the factors that cause frailty and,
      if possible, modify or prevent the initial decline using nutritional and other
      interventions. This requires careful monitoring, not only using the traditional
      markers of renal disease including urea and creatinine, but also using
      instruments that measure functional ability. These issues are discussed under the
      headings prevention, documentation and planning.

PMID- 11583375
TI  - Geriatric nephrology and urology literature.

PMID- 11583374
TI  - Utility and limitations of biochemical parameters in the evaluation of
      hyponatremia in the elderly.
AB  - We evaluated in 110 consecutive elderly hyponatremic patients the value of
      traditional clinical and biochemical data and the place of a test infusion of 2
      liters isotonic saline over 24 hours, in establishing the etiology of the
      hyponatremia. The causes of hyponatremia were as follows: 31% SIADH patients, 23%
      patients with hyponatremia due to diuretics, 18% potomania patients, 15% salt
      depleted patients, 5% salt depleted SIADH patients, 5% patients with a salt
      loosing syndrome and 3% patients with hyponatremia of unknown origin. Several
      salt depleted (SD) and SIADH patients could be confounded. Usually, adults with
      SIADH show plasma uric acid values <4 mg/dL. In our elderly population, 41% of SD
      patients presented plasma uric acid <4 mg/dL, while 27% of SIADH patients showed
      plasma uric acid >4 mg/dL. Eighty-two percent of SD patients appeared to have
      plasma urea levels >30 mg/dL, but this was also the case in 21% of SIADH
      patients. Twenty-nine of the SD patients presented a urinary sodium >30 mEq/L,
      but all had fractional sodium excretion (FENa) lower than 0.5%. However, in
      SIADH, 42% of the patients presented also FENa <0.5%. Fractional excretion of
      urea (FE urea) below 50% was encountered in 82% of SD patients and FE urea above
      50% in only 52% of the SIADH patients. Plasma renin and aldosterone values were
      poorly discriminative. A test infusion with 2 liters isotonic saline over 24
      hours allowed a correct classification of all the patients. In about 2/3 of the
      population, administration of isotonic saline could be considered as useful (SD,
      most diuretic patients, potomania patients, salt loosing syndrome patients and
      some SD SIADH patients). A plasma sodium (PNa) increase of at least 5 mEq/L 24
      hours after saline infusion has been suggested as highly suggestive of SD.
      Nevertheless, 29% of our SD patients did not increase their PNa level by 5 mEq/L
      or more, while 30% of our SIADH patients did. PNa improved after 2 liters
      isotonic saline over 24 hours in 90 patients (85%) as opposed to 12 others (9
      SIADH and 3 diuretic patients), decreasing their plasma sodium. The isotonic
      saline infusion test, only allows a reliable classification of hyponatremia, as
      far as both PNa and sodium excretion were taken into account. In the SIADH group,
      6 patients (5%) presented initially manifest solute depletion and retained the 2
      liters isotonic saline before developping inappropriate natriuresis. Six patients
      showed a transient salt loosing syndrome with high fractional potassium excretion
      (FEK) and high calciuria, which differentiates them from thiazide patients
      presenting also high FEK, but low calciuria. These patients were also polyuric at
      admission. The saline infusion was well tolerated in all but 2 patients,
      developing mild pulmonary congestion at the end of the test infusion.

PMID- 11583376
TI  - Variable effects of nitrous oxide at multiple levels of the central nervous
      system in goats.
AB  - The direct and indirect effects of nitrous oxide (N2O) on the nociceptive
      responses of lumbar dorsal horn neurons, and the indirect effects on midbrain
      reticular formation (MRF) neurons and thalamic neurons were determined in goats
      anaesthetized with isoflurane. The technique used enabled the differential
      delivery of N2O to either the torso or the cerebral circulation, thus allowing
      assessment of the direct spinal and indirect brain effects of N2O. Systemic
      delivery of N2O appeared to have divergent effects, facilitating (4/11) or
      depressing (7/11) the responses of dorsal horn neurons. Such divergent effects
      were also observed when N2O was differentially delivered to the circulation in
      the torso (i.e. the spinal cord). Likewise, MRF and thalamic responses to noxious
      stimulation were variably affected by administration of N2O to the torso, with
      some cells facilitated (7/13 MRF neurons, 3/8 thalamic neurons) and others
      depressed (6/13 MRF neurons, 5/8 thalamic neurons). It appears that N2O has
      variable effects on the caprine CNS. The facilitatory action of N2O might
      partially explain why it is a relatively weak anaesthetic.

PMID- 11583377
TI  - An enzyme-linked immunosorbent assay using immonoaffinity-purified antigen in the
      diagnosis of caprine paratuberculosis and its comparison with conventional
      ELISAs.
AB  - An enzyme-linked immunosorbent assay (APA-ELISA) using an immunoaffinity-purified
      antigen was developed and compared with the unabsorbed and absorbed ELISA
      procedures, using a crude antigenic preparation, for its efficacy in detecting
      antibodies in goat sera against Mycobacterium ovium paratuberculosis. Serum
      samples from 89 goats belonging to three different flocks, two with a history and
      evidence of paratuberculosis and one without it, were subjected to each ELISA,
      which had been standardized on known positive sera from goats experimentally
      infected with paratuberculosis. Faecal culture, faecal examination and
      histopathology were used as indicators of infection. The diagnostic sensitivities
      of the unabsorbed, absorbed and APA-ELISA were 81.8%, 77.3% and 77.3% and the
      specificities were 90.6%, 93.7% and 96.8%, respectively. The positive predictive
      values of APA-ELISA (94.4%) was the highest, followed by absorbed ELISA (80.9%)
      and unabsorbed ELISA (72.0%). The negative predictive values for APA-ELISA,
      absorbed ELISA and unabsorbed ELISA were 93.0%, 92.7% and 93.8%, respectively.
      The results indicated the value of APA-ELISA in avoiding the need to absorb
      individual test sera with Mycobacterium phlei and giving more consistent results
      than the absorbed ELISA. The APA-ELISA was also better than the other two
      procedures in terms of specificity and positive predictive values.

PMID- 11583378
TI  - Clostridium infection (jisizheng) in yaks in Qinghai, China.
AB  - Since the mid-1980s, outbreaks of a disease characterized by a sudden onset,
      acute deaths and extensive haemorrhages in the viscera and digestive tract of
      yaks have been prevalent in Qilian, Qinghai, China. The disease is known as
      jisiheng by local people. Virulent Clostridium perfringens type A and Clostridium
      haemolytica were isolated from yaks that had died of jisizheng. In 1996 and 1997,
      yaks were immunized with a polyvalent inactivated vaccine against C. perfringens
      and with an inactivated vaccine against C. haemolyticum, and this prevented the
      occurrence of jisizheng.

PMID- 11583379
TI  - Demonstration of heterogeneous genotypes of Taylorella equigenitalis isolated
      from horses in six European countries by pulsed-field gel electrophoresis.
AB  - Forty-six isolates of Taylorella equigenitalis were analysed by pulsed-field gel
      electrophoresis (PFGE) after separate digestion of the genomic DNA with ApaI and
      with NotI. The isolates had been obtained from horses in six European countries
      and were classified into 18 genotypes. In Belgium, 2 genotypes were detected in 2
      isolates, in England 9 among 15, in Finland 2 in 2, in France 2 among 10, in
      Sweden 3 among 5, and in Switzerland 3 among 12. Two English isolates and 4
      French isolates gave identical PFGE profiles to those of Kentucky 188 from the
      United States. A common genotype was found in 5 isolates from Belgium and England
      and also in 10 isolates from France and Switzerland. The analysis of genomic DNA
      from 12 isolates of T equigenitalis obtained from male horses in France, Sweden
      and Switzerland gave no evidence of a sex-related difference in the genomic DNA.
      Genomic DNA from 11 streptomycin (STM)-susceptible isolates obtained in Sweden
      and Switzerland were classified into four genotypes by PFGE. Each of the six
      genotypes determined among the 17 isolates from these two countries had single
      phenotypes for resistance or susceptibility to STM.

PMID- 11583380
TI  - Activities of enzymes related to the malate-aspartate shuttle in the blood cells
      of thoroughbred horses undergoing training exercise.
AB  - The activities of the enzymes related to the malate-aspartate shuttle, which
      convert cytosolic NADH into mitochondrial NADH, were measured in red and white
      blood cells from thoroughbred horses undergoing continuous training (race horses)
      and compared with those in blood cells from riding horses. The activities of
      malate dehydrogenase (MDH), a rate-limiting enzyme for the malate-aspartate
      shuttle, were significantly elevated in the white blood cells (WBC) from race
      horses compared with those from riding horses. There were no significant
      differences in the activities of the enzymes in the red blood cells between race
      horses and riding horses. This increase in the MDH activity in their WBC is
      considered to reflect the increased metabolic activity in the race horses
      resulting from the training.

PMID- 11583381
TI  - Preliminary epidemiological and clinical observations on Shimao Zheng (fleece
      eating) in goats and sheep.

PMID- 11583382
TI  - Influence of plasma proteins on erythrocyte aggregation in three mammalian
      species.
AB  - The aggregation capacity of human erythrocytes lies between that of the non
      aggregating bovine erythrocytes and the remarkably aggregating equine ones. As
      the ability to aggregate is attributed to cell factors and the composition of the
      plasma proteins, the role that plasma proteins play in the aggregation process in
      these three species was studied. Washed erythrocytes were suspended in phosphate
      buffered saline (PBS; pH 7.4, 300 mOsm/L) plus polyvinylpyrrolidone (PVP) in a
      suitable concentration to obtain an average intensity of aggregation (control
      media). The superimposed effect of replacing 80% of the medium by either
      autologous plasma, serum or albumin solution was studied. The plasma proteins
      appeared to enhance aggregation by human and equine erythrocytes, but impaired
      this process in bovine erythrocytes. Some evidence was obtained supporting the
      existence of serum factors capable of reducing aggregation of erythrocytes in
      cattle and it was concluded that the non-aggregating behaviour of bovine
      erythrocytes may be due to the cells interacting particularly with the
      macromolecules in the serum.

PMID- 11583384
TI  - Rationale for selective neck dissection in tumors of the upper aerodigestive
      tract.

PMID- 11583383
TI  - Biochemical alterations in the blood plasma of rats associated with
      hepatotoxicity induced by Eupatorium adenophorum.
AB  - Eupatorium adenophorum (Crofton weed), a native of Central America. has appeared
      as a major weed in several areas in different parts of the world. Horses that eat
      this plant are poisoned on prolonged exposure. Toxicity due to consumption of
      this plant by other grazing animals is not clear. Administration of freeze-dried
      leaf powder to mice results in hepatotoxicity. Earlier attempts to produce
      toxicity in rats using the leaves of this plant were not successful. In the
      present study, administration of oven-dried E. adenophorum leaves collected at
      the flowering stage elicited hepatotoxicity in rats. The affected animals had a
      marked increase in the concentration of plasma bilirubin and in the activities of
      5'-nucleotidase, alkaline phosphatase, aspartate aminotransferase, alanine
      aminotransferase and lactate dehydrogenase. There were no significant differences
      in plasma creatinine, urea or total protein values in the affected animals
      compared to controls. The livers of the affected animals had focal areas of
      necrosis throughout the parenchyma and hepatocytes showed megalocytosis. The bile
      ducts were dilated and the epithelium showed degenerative to necrotic changes.
      The alterations in bilirubin, enzymes and histopathological changes imply
      cholestasis and liver injury.

PMID- 11583385
TI  - Metastatic cervical lymph nodes from urogenital tract carcinoma: a diagnostic and
      therapeutic challenge.

PMID- 11583386
TI  - Are some ear drops ototoxic or potentially ototoxic?
AB  - In this article we review the literature concerning the capacity of certain
      substances to cause ototoxicity when administered topically. The ototoxicity
      experimentally observed in animals only occurs in humans under certain
      circumstances. It is concluded that many of these products. which are commonly
      used for treatment in humans, are ototoxic in animals and may also be ototoxic in
      humans. Therefore, the use of other substances which have the same action but are
      not ototoxic

PMID- 11583387
TI  - Drug-induced otoxicity: current status.
AB  - We carried out a review of the literature published over the last 10 years on
      drug-induced ototoxicity by means of a Medline search using the terms 'clinical
      ototoxicity' for the period January 1990 to September 2000 and found 414
      published articles. In order to summarize the content of these articles, we asked
      ourselves a series of nine questions and answered them based on the most widely
      held views and those we considered of greatest interest in the articles reviewed.
      The questions asked were: what are the most commonly used ototoxic drugs? what is
      the site of action of ototoxic drugs? what is the importance of the dose and
      dosing interval? does age influence ototoxicity? are all humans equally prone to
      the ototoxic effects of drugs? are there substances that are protective against
      ototoxicity? can hearing loss be monitored? should hearing loss be attributed to
      ototoxic drugs in all cases? and is ototoxicity in animals the same as in humans?

PMID- 11583388
TI  - Effects of neuropeptide Y on cochlear blood flow in guinea pigs.
AB  - The aim of this study was to clarify the effects of neuropeptide Y (NPY) on
      cochlear blood flow (CBF) in pigmented guinea pigs. NPY was administered with or
      without noradrenaline (NA) by systemic perfusion or perilymphatic local
      perfusion, and CBF was measured using a laser Doppler flowmeter. The systemic and
      perilymphatic administrations of NPY with NA induced greater prolongation of the
      increase in and recovery of CBF than the administration of NA or NPY alone.
      Continuous reduction in CBF induced by NPY may play an important role in the
      pathogenesis of stress-induced sensorineural hearing losses, such as sudden
      deafness.

PMID- 11583389
TI  - Ginkgo biloba extract EGb 761 or pentoxifylline for the treatment of sudden
      deafness: a randomized, reference-controlled, double-blind study.
AB  - In a randomized, prospective, double-blind study involving 72 patients, the
      therapeutic efficacy of ginkgo extract EGb 761 (n = 37) was compared to that of
      pentoxifylline (n = 35) for the treatment of sudden deafness. The two therapeutic
      schedules were equally well tolerated and showed a statistically significant
      equivalence in improvement or in return to normal of the auditory thresholds in
      the two patient groups. Furthermore, no differences were found between the
      treatment groups with regard to the criteria for a return to normal of speech
      discrimination and reduction of the tinnitus which arose at the same time as the
      sudden hearing loss. The patient's subjective assessment of the treatment with
      regard to improvement in hearing and reduction in tinnitus suggested that Ginkgo
      biloba extract was more beneficial than pentoxifylline. In summary, it was shown
      that treatment of sudden deafness with ginkgo special extract EGb 761 was as
      effective as treatment with pentoxifylline.

PMID- 11583390
TI  - The use of Preyer's reflex in evaluation of hearing in mice.
AB  - Preyer's reflex, the elicitation of startle response to auditory stimuli, has
      been widely used for the evaluation of hearing in rodents and other animals.
      Surprisingly, however, the sensitivity and specificity of Preyer's reflex in the
      assessment of hearing has not been adequately studied. The aim of this study was
      to investigate the utility of Preyer's reflex in the evaluation of auditory
      function in mice. Forty-six adult albino mice on an FVB background with variable
      hearing loss were used for this study. Two different methods for eliciting a
      Preyer's reflex were tested: a handclap and a sharp metallic sound. The reflex
      was considered positive when a rapid movement of the whole body of the animal was
      clearly noticed. Thereafter, the mice underwent auditory brain stem response
      (ABR) testing with broadband clicks. The presence or absence of Preyer's reflex
      was compared with the corresponding ABR thresholds. Five of the 46 animals
      studied (11%) showed a negative Preyer's reflex, while the remaining 41 animals
      demonstrated a positive Preyer's reflex. There was no difference between the
      abilities of the two different stimuli to elicit a Preyer's reflex. The click
      evoked ABR thresholds in the test animals varied between 8 and 136 (mean 50) dB
      sound pressure level (SPL). Preyer's reflex was positive in all animals with an
      ABR threshold of < or = 76 dB SPL, but was absent in animals with an ABR
      threshold of > or = 81 dB SPL. Preyer's reflex is effective for identifying
      profound sensorineural hearing loss in experimental mice, but is insensitive for
      detecting less severe auditory dysfunction. For definitive hearing assessment,
      and for defining the hearing thresholds. objective electroacoustical methods such
      as ABR should be used.

PMID- 11583391
TI  - Magnetic materials in otoliths of bird and fish lagena and their function.
AB  - The mystery of the homing ability of pigeons has been the subject of much
      interest and it is widely believed that information from the earth's magnetic
      field may be involved. However, no specific magnetic sensory organ has yet been
      identified. The recent finding of magnetic materials in the lagenal otolith of
      fish and birds raises the possibility that these structures may be key elements
      in the elusive magnetic sensory system. For the elemental analysis of materials X
      ray fluorescence using synchrotron radiation is one of the most powerful
      techniques available and was used in this study for analysis of the otoliths. By
      comparing the compositions of the three different kinds of otoliths among several
      species of sea fish and birds, we found that the saccular and utricular otoliths
      rarely contain detectable levels of iron but that iron is present in significant
      quantities in the lagenal otoliths of the birds. The lagenal otolith comprises
      tiny magnetic particles of low inertia that are displaced by imposed magnetic
      fields, providing the animal with geomagnetic sensory input, from which the brain
      would infer navigational information.

PMID- 11583392
TI  - Induction of mucin and adhesion molecules in middle ear mucosa.
AB  - We hypothesized that inflammation molecules induce the secretory hyperplasia
      characteristic of otitis media with effusion (OME). The purpose of the present
      study was to compare the location of inflammation molecules and mucin in the
      middle ear mucosa of both normal and OME ears. OME was created by bisection of
      the tensor veli palatini muscle in germ-free rabbits, and the development of
      middle ear effusion was confirmed by otomicroscopy and tympanometry. Ventilation
      tubes (VTs) were inserted in half of the ears. The animals were decapitated after
      8 weeks, and serial sections of the middle ear mucosae were either periodic acid
      Schiff (PAS)-stained or stained immunohistochemically for inflammation molecules
      or mucins. The length of stained epithelium was measured and related to the total
      epithelial length. There was a striking resemblance between mucin-type MUC5B- and
      PAS-positive epithelium and areas positive for the chemoattractant inflammation
      molecules intercellular adhesion molecule-1 (ICAM-1) and RANTES (reacted upon
      activation, normal T expressed and secreted). The percentages of ICAM-1- and PAS
      stained epithelium were significantly higher in OME ears than in normal ears. OME
      ears treated with VTs also contained significantly more PAS-positive epithelium
      than normal ears, but less than OME ears. Based on the spatial and temporal
      coincidence between ICAM-1 and mucin, it is suggested that: (i) inflammation may
      initiate and maintain the hypersecretory state of the middle ear mucosa which is
      presumably responsible for the chronicity of OME; and (ii) that MUC5B is a major
      mucin component of OME effusions.

PMID- 11583393
TI  - Cholesteatoma: a morphologic study of stratum corneum lipids.
AB  - Two different lipid-retaining fixation techniques permitted electron microscopic
      visualization of both intra- and extracellular lipids in cholesteatoma epithelium
      obtained from 25 patients. An increased number of intracellular lipid-containing
      Odland bodies was demonstrated, with a maximum in the basal layer of the stratum
      granulosum, while the superior layer contained substantially fewer organelles
      than are found in normal skin. At the stratum granulosum/stratum corneum
      interface lipids secreted from Odland bodies were found in sac-like invaginations
      along the cell membrane but premature exocytosis was also frequently observed. In
      the intercellular spaces of the stratum corneum, multiple long sheets of lamellar
      structures interrupted by slits or pores enclosed the keratinized corneocytes.
      The intercellular spaces seemed narrow and an extracellular barrier was not found
      until well above the stratum granulosum/stratum corneum interface. A similar
      distribution of Odland bodies and structure of intercellular lipids can occur in
      several dermatoses, where the formation and maintenance of the cutaneous
      permeability barrier are defective.

PMID- 11583394
TI  - Radical cavities and cochlear implantation.
AB  - Profoundly deaf patients with chronic suppurative otitis media have been
      contraindicated for cochlear implantation in the past. Complications such as
      infection of the radical cavity, fat necrosis, skin flap problems, change in
      electrode position and cholesteatoma have occurred in subjects with radical
      cavities. The aim is to create a dry, self-cleansing, infection-free cavity. This
      is essential in patients about to receive a cochlear implant, as infection may be
      introduced into the cochlea at the implantation site and destroy any remaining
      neural elements. The aim of this paper was to show that it is possible to
      obliterate the radical cavity and perform cochlear implantation using a one-step
      surgical technique. Eight patients suffering from long-term bilateral chronic
      middle ear diseases with chronic sepsis leading to severe hearing impairment
      underwent cochlear implant surgery. No major complications were observed in these
      subjects.

PMID- 11583395
TI  - The effect of betahistine on vestibular habituation: comparison of rotatory and
      sway habituation training.
AB  - This study was designed to investigate the effect of histaminergic agonists and
      antagonists on the acquisition of vestibular habituation. The experimental
      animals, pigeons, were subjected to unilateral rotatory and sway habituation
      training sessions. The habituation of postural reflexes and post-rotatory head
      nystagmus was assessed. Vestibular habituation in the control group was achieved
      by adopting the kinetic reflex posture after approximately 9 training sessions,
      and after 10 and 14 training sessions, respectively for 50% reduction of the
      total number of beats (TNB) and the duration of post-rotatory head nystagmus. In
      the sway adaptation test control pigeons needed nearly 15 training sessions while
      pigeons receiving betahistine adapted after approximately 8 sessions.
      Administration of histamine and, most notably, betahistine accelerated the
      process, while both H1 and H2 antagonists (clemastine, cimetidine) tended to
      retard it, indicating a less significant contribution of H2 receptors. The
      cholinergic agent physostigmine strongly retarded habituation while the
      anticholinergic agent scopolamine markedly accelerated it. In addition the
      adrenomimetic agent ephedrine also accelerated habituation while the adrenolytic
      agent droperidol retarded reduction of nystagmus beats. The results indicate that
      histaminergic receptors play a significant role in the vestibular habituation
      mechanism but are intricately involved with other types of receptors. Betahistine
      is clearly the agent of choice for attenuating vestibular effects.

PMID- 11583396
TI  - Control of symptoms in patients with Meniere's disease using middle ear pressure
      applications: two years follow-up.
AB  - The effects of middle ear pressure pulses were studied in 37 patients with a
      diagnosis of definite Meniere's disease and active vestibular symptoms, 31 of
      whom had failed to respond to medical treatment including diuretics prior to
      pressure treatment. The number of vertigo spells during the 6 months prior to
      treatment and for 6, 18 and 24 months after the start of treatment were
      evaluated. The functionality level scores were three or worse according to the
      American Academy of Otolaryngology--Head and Neck Surgery (AAO-HNS) criteria. The
      results of the study were as follows: 19 patients experienced freedom from
      vertigo spells; 15 patients reported a significant decrease in the frequency of
      vertigo spells; and 3 patients did not respond to pressure treatment and were
      subjected to gentamicin injections, I of whom consequently became deaf in the
      affected ear. No patient became worse in connection with pressure treatment. With
      the exception of the three patients who did not respond to pressure treatment,
      all patients reported an improvement in functionality of at least two levels
      according to the AAO-HNS functionality scale. No side effects or adverse events
      were observed during the 2 years of pressure treatment. Overall, the results
      indicate that pressure treatment provides efficient control of symptoms in
      patients with intractable forms of Meniere's disease without producing any
      adverse effects on the inner ear.

PMID- 11583397
TI  - Labyrinthine fistula detection: the predictive value of vestibular symptoms and
      computerized tomography.
AB  - A retrospective case record study of 20 patients in Oslo operated on for chronic
      otitis media with labyrinthine fistula between 1986 and 1999 was performed in
      order to estimate the incidence of, and identify predictors for, labyrinthine
      fistulas. The incidence of fistula was 0.3 per 100 000, with a median age at
      diagnosis of 37 years. The median duration of chronic otitis media prior to
      labyrinthine fistula detection was significantly correlated with age at surgery.
      Subjective hearing loss (90%), otorrhoea (65%) and dizziness (50%) were
      presenting symptoms. Modified canal-wall-down mastoidectomy was performed in all
      patients. Preoperative hearing levels could not predict postoperative hearing
      outcome. Positive signs of fistula were found in only 4 patients (20%).
      Correspondingly, computerized tomography (CT) diagnosed the fistula in 11
      patients (55%). The seven patients presenting without dizziness and with a
      negative CT scan and fistula test were characterized by lower age, absence of
      previous middle ear surgery, lower preoperative pure-tone thresholds for bone
      conduction and better hearing outcome after surgery. In conclusion, the
      identification of a younger group of patients presenting with fewer symptoms
      indicates that fistulas should be suspected in all patients undergoing surgery
      for chronic middle ear and mastoid disease.

PMID- 11583398
TI  - Cross-sectional shapes of the internal auditory canal in patients with acoustic
      neuromas.
AB  - Cross-sectional images of the internal auditory canal (IAC) were investigated in
      23 patients with acoustic neuroma in order to clarify the widening of the IAC.
      The area of the IAC and the ratio of areas (neuroma side:normal side) were
      calculated. The shape of the IAC was fitted by an ellipse to obtain the length of
      the axes and the direction of the long axis. The area of the IAC was 34.2+/-12.2
      mm2 in the neuroma side and 18.1+/-4.8 mm2 in the normal side. The neuroma side
      was larger than the normal side in all patients, and the mean ratio of areas was
      1.9. However, the degrees of cochlear and vestibular damage did not correlate
      with the ratio of areas. The mean ratio of axes of the approximated ellipse was
      1.17+/-0.09 in the neuroma side and 1.14+/-0.10 in the normal side; however, no
      significant difference was seen between the ratio of axes. The directions of the
      long axes were not always consistent with the positions of the originating nerves
      of the tumour. Referring to hypothetical models of enlargement of the IAC, our
      data suggest that the widening of the IAC in the acoustic neuroma was expansive.
      The data also indicated that symptoms of the acoustic neuroma were caused not
      only by compression of the nerves but also by other mechanisms, such as vascular
      insufficiency to the inner ear.

PMID- 11583399
TI  - High-resolution petrous bone imaging using multi-slice computerized tomography.
AB  - Multi-slice computerized tomography (MSCT) is considered to provide superior
      image quality. We defined a data acquisition protocol for high-resolution (HR)
      temporal bone imaging using MSCT and assessed its impact on data acquisition and
      post-processing (PP). The data acquisition protocol was defined in cadaveric
      phantom studies performed by MSCT and subsequently applied to 38 patients
      referred for temporal bone assessment. The parameters image quality and
      diagnostic value of MSCT data were assessed for the cross-sectional source images
      as well as for 2-dimensional (2D) reformations and 3-dimensional (3D)
      reconstructions by 3 radiologists by comparison with incremental HR scans of 17
      patients with suspected middle ear disorders. The data acquisition protocol
      yielded HR images with an excellent detail resolution and a comparable image
      quality of cross-sectional scans and related orthogonal reformations. MSCT
      achieved higher scores for image quality and diagnostic value (p < 0.001, t-test)
      than incremental HR CT with regard to both 2D and 3D reconstructions. MSCT
      improves the image quality of HR cross-sectional scans as well as that of 2D and
      3D PP techniques in petrous bone imaging. The radiation exposure of the eye
      lenses is increased by MSCT as gantry angulation is not yet possible in the
      helical scan mode.

PMID- 11583400
TI  - Remarkable attachment of lactoferrin to Streptococcus pyogenes during acute
      pharyngotonsillitis.
AB  - The purpose of this study was to establish whether lactoferrin (hLf) attached to
      Streptococcus pyogenes, one causative agent of acute pharyngotonsillitis (AT),
      during the course of the disease. Bacterial samples were obtained from the
      tonsillar surfaces of 7 patients (6 females, 1 male; median age 26 years; range
      16-50 years) suffering from AT who were culture-positive for S. pyogenes and from
      5 healthy adult controls who were culture-negative for this pathogen. Using gold
      labelled antiserum against S. pyogenes and hLf, this pathogen and other bacteria
      on the tonsillar surfaces coated with hLf could be identified by tracing the gold
      particles in a transmission electron microscope. In healthy adults, 8% (median
      value; range 6-12%) of the surface tonsillar bacteria were coated with hLf. In AT
      patients, 59% (median value; range 42 67%) of S. pyogenes were coated with hLf,
      in contrast to 9% (median value; range 0-26%) of all other bacteria (p < 0.01).
      This study hints that hLf might participate in recovery from AT in several ways,
      e.g. by binding to the S. pyogenes pathogens, in addition to its well-known
      virtue of iron-binding capacity.

PMID- 11583401
TI  - Does metal coating improve the durability of silicone voice prostheses?
AB  - Voice prostheses, which are used for voice rehabilitation in cancer patients
      after laryngectomy, usually become colonized with a mixed biofilm of bacteria and
      Candida after 2-4 months and lose their efficiency. It is essential to ensure the
      stability and biocompatibility of these implants. With the aid of surface frame
      analysis we have shown that local antifungal treatment is inadequate for
      eliminating the deep infiltration and encapsulation of Candida colonies in
      silicone. A surface that prevents the adhesion of microorganisms is required.
      Because of its special properties there are few methods available for coating
      silicone. We employed, for the first time, a new method of surface modification
      using anodic vacuum arc coating. Using this method it was possible to obtain a
      solid film of gold or titanium metal with a layer thickness < 100 nm. Resistance
      against Candida colonization and destruction of coated prostheses were tested
      both in vitro and in vivo. A titanium coating seemed to provide the optimal
      solution to the problem, because surface adhesion and the smoothness of the
      material appeared to be superior to those of a gold coating.

PMID- 11583402
TI  - The clinical presentation of non-hodgkin lymphomas of the major salivary glands.
AB  - The aim of this study was to examine the clinical presentation of patients with
      malignant lymphoma of the major salivary glands. In a retrospective study, 26
      patients with a non-Hodgkin lymphoma (NHL) of the major salivary glands were
      examined. The results showed a distinct preference for the female gender. Two
      groups with clinical differences were observed depending on lymphoma
      manifestation as either extranodal-parenchymal (extranodal) or with intra- or
      periglandular (nodal) lymph node disease. Differences between these two groups
      existed with regard to the length of clinical history, recurrent vs continuously
      progressing symptoms and presentation on ultrasound examination (multiple masses
      compared to solitary masses). Patients with an extranodal lymphoma always showed
      disease limited to the affected gland, whereas those patients with a nodal
      lymphoma presented with stage II or higher (Ann Arbor Classification). In these
      patients, local recurrence was also five times higher (5/13; 38.4%) than in
      patients with an extranodal lymphoma (1/13; 7.7%). In 1 patient (7.7%) with
      extranodal lymphoma, dissemination was observed, compared to 6/13 patients
      (46.2%) in the group with nodal disease. Seven out of 13 patients (53.8%) with
      nodal disease died due to lymphoma spread and 1/13 (7.7%) of the patients with
      extranodal disease. There seem to be distinct clinical differences in the course
      of patients with NHL of the major salivary glands, depending on extranodal or
      nodal disease presentation. The histopathological diagnosis, with special
      recognition of the particular lymphoma pathogenesis, constitutes an important
      prognostic factor in these patients.

PMID- 11583403
TI  - Facial nerve paralysis in temporal bone fractures: outcomes after late
      decompression surgery.
AB  - The aim of this paper was to address some of the unanswered questions regarding
      management of facial nerve paralysis in temporal bone fractures (TBF), such as
      the outcomes after late facial nerve decompression surgery. The study design was
      a retrospective review of a consecutive clinical series. Thirteen patients who
      underwent late decompression surgery for facial nerve paralysis due to TBF
      involving the perigeniculate ganglion region were analyzed. Patients were
      operated on 27-90 days after trauma. A transmastoid extralabyrinthine approach
      was used in all cases. Facial nerve-sheath slitting was performed routinely.
      Normal or subnormal facial nerve function (HB 1 or HB 2) was achieved in 7/9
      cases (78%) evaluated at > or = 1 year after surgery. Good functional results
      were also obtained in two patients operated on 3 months after trauma. Bases on
      the outcomes observed in the present series, in patients unable to be operated on
      early, presenting 1 to 3 months with >95% denervation on EnoG, facial nerve
      decompression may have a beneficial effect.

PMID- 11583404
TI  - Navigation in medical Internet image databases.
AB  - The world wide web (WWW) changes common ideas of database access. Hypertext
      Markup Language allows the simultaneous presentation of information from
      different sources such as static pages, results of queries from) databases or
      dynamically generated pages. 'Therefore, the metaphor of the WWW itself as a
      database was proposed by Mendelzon and Nlilo in 1998. Against this background the
      techniques of navigation within WWW-databases and the semantic types of their
      queries has e been analysed. Forty eight image repositories of different types
      and content, but all concerning medical essence, have been found by search
      engines. Many different techniques are offered to enable navigation ranging from
      simple HTML-link-lists to complex applets. The applets in particular promise an
      improvement for navigation. Within the meta-information for querying, only ACR-
      and UMLS-encoding were found, but not standardized vocabularies like ICD10 or
      Terminologia Anatomica. UMLS especially shows that a well defined thesaurus can
      improve navigation. However, of the analysed databases only the UMLS
      'metathesaurus' is currently implemented without providing additional navigation
      support based on the UMLS 'semantic network'. Including the information about
      relationships between the concepts of the metathesaurus or using the UMLS
      semantic network could provide a much easier navigation within a network of
      concepts pointing to multimedia files stored somewhere in the WWW.

PMID- 11583405
TI  - Health care providers on the World Wide Web: quality of presentations of surgical
      departments in Germany.
AB  - It is becoming increasingly common for health care providers to present
      information on the World Wide Web (WWW). Patients, as well as health care
      professionals, do not really know what they can expect today. Many quality
      criteria are proposed for the assessment of medical Internet sites focusing
      mainly on structure and content management. The objective of this study was to
      assess the quality of presentations by health care providers on the WWW and to
      detect strengths and weaknesses with regard to potential target groups, patients,
      colleagues, and students. A sample of 171 presentations was randomly selected in
      March 2000 from a collection of 469 surgical departments in Germany. Medical
      doctors undergoing a full-time training in medical informatics rated the
      presentations. A previously evaluated questionnaire was used to assess the
      presentations with regard to 12 criteria about content and technical features.
      For each criterion the categories 'very good', 'sufficient', and 'insufficient'
      could be used. Twenty medical doctors assessed 168 presentations with one to
      seven valuations per presentation. Three presentations could not be accessed at
      the time of evaluation. Sixty-eight per cent of the median values of each
      criterion were rated as insufficient. The only criteria rated sufficient or
      better in at least 50% were: employees/map, survey of offered medical services,
      navigation, and layout. University hospitals and heart centres achieved
      significantly better results than regional hospitals. In conclusion, the quality
      of provider information on the W WW is unsatisfactory. Most surgical departments
      do not provide information that could help patients to choose their physicians.
      The criteria set developed here could be a useful tool for a target-group
      oriented self-assessment of provider presentations on the World Wide Web.

PMID- 11583406
TI  - Discovery of association rules in medical data.
AB  - Data mining is a technique for discovering useful information from large
      databases. This technique is currently being profitably used by a number of
      industries. A common approach for information discovery is to identify
      association rules which reveal relationships among different items. In this
      paper, we use this approach to analyse a large database containing medical-record
      data. Our aim is to obtain association rules indicating relationships between
      procedures performed on a patient and the reported diagnoses. Random sampling was
      used to obtain these association rules. After reviewing the basic concepts
      associated with data mining, we discuss our approach for identifying association
      rules and report on the rules generated.

PMID- 11583407
TI  - On the use of EEG features towards person identification via neural networks.
AB  - Person identification based on spectral information extracted from the EEG is
      addressed in this work a problem that has not yet been seen in a signal
      processing framework. Spectral features are extracted non-parametrically from
      real EEG data recorded from healthy individuals. Neural network classification is
      applied on these features using a Learning Vector Quantizer in an attempt to
      experimentally investigate the connection between a person's EEG and genetically
      specific information. The proposed method, compared with previously proposed
      methods, has yielded encouraging correct classification scores in the range of
      80% to 100% (case-dependent). These results are in agreement with previous
      research showing evidence that the EEG carries genetic information.

PMID- 11583408
TI  - An integrated architecture for deploying a virtual private medical network over
      the web.
AB  - In this paper we describe a pilot architecture aiming at protecting Web-based
      medical applications through the development of a virtual private medical
      network. The basic technology, which is utilized by this integrated architecture,
      is the Trusted Third Party (TTP). In specific, a TTP is used to generate,
      distribute, and revoke digital certificates to/from medical practitioners and
      healthcare organizations wishing to communicate in a secure way. Digital
      certificates and digital signatures are, in particular, used to provide peer and
      data origin authentication and access control functionalities. We also propose a
      logical Public Key Infrastructure (PKI) architecture, which is robust, scalable,
      and based on standards. This architecture aims at supporting large-scale
      healthcare applications. It supports openness, scalability, flexibility and
      extensibility, and can be integrated with existing TTP schemes and
      infrastructures offering transparency and adequate security. Finally, it is
      demonstrated that the proposed architecture enjoys all desirable usability
      characteristics, and meets the set of criteria, which constitutes an applicable
      framework for the development of trusted medical services over the Web.

PMID- 11583409
TI  - Incorporating family and social structures into clinical documentation and
      retrieval.
AB  - Referencing familial and social relationships between patients supplies valuable
      information for the retrieval and interpretation of clinical data. We present a
      technique for the incorporation of patient relations into data retrieval that
      takes into account the specific properties of routinely collected clinical data.
      In most clinical databases, family relations are documented in a fragmentary
      manner at best. Furthermore, clinical retrieval systems do not support inter
      patient queries in most cases. Our model is designed to formulate direct
      relations between patients and to identify patients as members of either
      temporary or persistent communities. In this way, the model supplies information
      on both genetic and social relations.

PMID- 11583410
TI  - Induction of sexual activity of male creole goats in subtropical northern Mexico
      using long days and melatonin.
AB  - The aim of this study was to determine whether the sexual activity of local male
      Creole goats in subtropical Mexico can be induced during the non-breeding season
      by a long-day treatment followed by insertion of two melatonin implants. The
      experiment was carried out in the Laguna region in the State of Coahuila, Mexico
      (26 degrees N). Fourteen male goats were allocated to two balanced groups (n = 7
      each) according to body and testicular weights. Males were kept together in two
      separate groups and fed lucerne hay for ad libitum intake and 300 g of commercial
      concentrate and had free access to water and mineral blocks. The control group
      remained in open sheds under natural photoperiod and ambient temperature
      conditions. The experimental group was placed in a light-proof building and
      exposed to 2.5 mo of long days (16 h of light/d) from November 1 to January 15.
      On January 16, each male received two s.c. melatonin implants and was exposed to
      natural photoperiodic changes in an open shed. In the control group, testicular
      weight exhibited seasonal variations; the highest value occurred on May 30 (146
      +/- 10 g). Treated males reached maximum testicular weight earlier (March 15; 147
      +/- 11 g), and sperm quality from January to March was higher than that observed
      in the control group (P < 0.05). Treatment caused an increase in LH pulse
      frequency (2.0 +/- 0.5 vs 0.3 +/- 0.2 pulse/8 h in February, 4.6 +/- 1.1 vs 0.1
      +/- 0.1 pulse/8 h in March; experimental vs control group, respectively). In the
      control group, plasma testosterone remained low until mid-June and increased
      thereafter to remain elevated until the end of the study. In the experimental
      group, elevated plasma testosterone was observed from February to April and from
      July to November. Treating male goats in subtropical latitudes with artificial
      long days and melatonin can induce an intense sexual activity during the natural
      nonbreeding season.

PMID- 11583411
TI  - Inclusion of an intravaginal progesterone insert plus GnRH and prostaglandin
      F2alpha for ovulation control in postpartum suckled beef cows.
AB  - Four experiment stations (IL, KS, MN, and MO) conducted experiments to determine
      effects of introducing a CIDR (controlled internal device release) into an
      ovulation control program for postpartum suckled beef cows. Five hundred sixty
      cows were assigned randomly to two treatments: 1) 100 microg of GnRH (i.m.)
      followed in 7 d with 25 mg of PGF2alpha, followed in 48 h by a second injection
      of GnRH and one fixed-time insemination (Cosynch; n = 287) or 2) Cosynch plus one
      CIDR during the 7 d between the first injection of GnRH and PGF2alpha (Cosynch+P;
      n = 273). Cows at three stations were inseminated at the time of the second GnRH
      injection (n = 462), whereas 98 cows at the fourth station were inseminated 16 to
      18 h after that injection. Blood samples were collected at d -17, -7, 0, and 2
      relative to PGF2alpha to determine concentrations of progesterone.
      Ultrasonography was used to monitor follicle diameter on d 2 and to determine the
      presence of an embryo at 30 to 35 d after insemination. Pregnancy rates were
      greater (P < 0.05) for Cosynch+P- (58%) than for Cosynch-treated (48%) cows. No
      station x treatment interaction occurred; however, cows at MO (62%) and KS (60%)
      had greater (P < 0.05) pregnancy rates than those at IL (47%) and MN (44%). Cows
      that had follicles > 12 mm on d 2 had greater (P < 0.01) pregnancy rates than
      those with follicles < or = 12 mm regardless of treatment. Pregnancy rates were
      similar between Cosynch and Cosynch+P treatments when cycling cows had elevated
      concentrations of progesterone at d 0, but pregnancy rates were greater (P <
      0.05) in the Cosynch+P (79%) than in the Cosynch (43%) treatment when cycling
      cows had low concentrations of progesterone on d 0 (at PGF2alpha injection).
      Similarly, among noncycling cows, pregnancy rates were greater (P < 0.05) in the
      Cosynch+P (59%) treatment than in the Cosynch (39%) treatment. Cows in greater
      body condition at the onset of the breeding season experienced improved (P <
      0.001) overall pregnancy rates. Pregnancy rates for cows that calved > 50 d
      before the onset of the breeding season were greater (P < 0.01) than those for
      cows that calved < or = 50 d. Thus, treatment of suckled cows with Cosynch
      yielded acceptable pregnancy rates, but addition of a CIDR improved pregnancy
      rates in noncycling cows. Body condition and days postpartum at initiation of the
      breeding season affected overall efficacy of the Cosynch and Cosynch+P protocols.

PMID- 11583412
TI  - Effect of varying carbohydrate and fat content of milk replacer on body
      composition of Holstein bull calves.
AB  - The objective of this study was to determine the effect of varying concentrations
      of dietary fat and carbohydrate on changes in body composition of Holstein bull
      calves fed under isocaloric and isonitrogenous intake conditions. Thirty-two
      calves were assigned to a randomized block design with three dietary treatments,
      eight calves per treatment, and one baseline group of eight calves. Animals were
      reared from birth to 85 kg live BW (SEM = 0.57). All calves began treatments
      between 2 and 6 d of age. Three different milk replacer treatment diets were
      designed to deliver 14.8 (low fat, LF), 21.6 (medium fat, MF), or 30.6% of DM
      (high fat, HF) fat; 55.3, 46.7, or 35.4% of DM lactose; and 23.5, 24.8, or 27.0%
      of DM CP, respectively. Gross energy values were 4.62, 5.09, and 5.77 Mcal/kg for
      the LF, MF, and HF milk replacers, respectively. From d 1 to 14, calves were
      offered 0.24 Mcal intake energy/kg BW(0.75), adjusted weekly based on increases
      in BW, and 0.28 Mcal intake energy/kg BW(0.75) from d 15 to slaughter. Dry feed
      was not offered. Dry matter, energy, CP, and fat intakes were 55.2 kg, 257.6
      Mcal, 13.0 kg, and 8.2 kg; 52.8 kg, 268.8 Mcal, 13.1 kg, and 11.4 kg; and 46.8
      kg, 270.3 Mcal, 12.6 kg, and 14.3 kg for the LF, MF and HF treatments,
      respectively. Energy and CP intakes did not differ among treatments (P = 0.63 and
      0.79, respectively). Fat and DMI were different among treatments (P = 0.001 and
      0.02, respectively). Empty BW gains were 0.61, 0.61, and 0.65 kg/d for LF, MF,
      and HF, respectively, and were not different among treatments (P = 0.27). Empty
      body CP, water, and ash gain were not different among treatments (P = 0.65, 0.99,
      and 0.57, respectively). Empty body retained energy and fat gain were 27.2 and
      57.7% greater for calves fed the HF than for those fed the LF diet (P = 0.06 and
      0.006, respectively). Fat as a percentage of the whole empty body on a water-free
      basis was lower for calves consuming the LF diet (28.6%) than for those fed the
      HF diet (34.6%), whereas percentage of CP on an empty body, water-free basis was
      greater for calves consuming the LF diet (59.2%) than for those fed the HF diet
      (54.9%) (P = 0.006). The results of this study demonstrated that, under
      isocaloric and isonitrogenous intake conditions, equivalent dietary energy from
      fat compared to carbohydrate, above 15% fat, has no beneficial purpose unless
      additional fat deposition is required in the animal. Further, the data
      demonstrate significant changes in body composition independent of growth rate.

PMID- 11583413
TI  - Effect of hybrid, maturity, and mechanical processing of corn silage on intake
      and digestibility by beef cattle.
AB  - A study involving a 2 x 2 x 2 factorial arrangement of treatments was conducted
      to evaluate effects of hybrid (Pioneer 3335 and 3489), maturity (half milkline
      and blacklayer), and mechanical processing (field chopper with and without on
      board rollers engaged) on intake and digestibility of corn silage. Forty Angus
      steers (322 +/- 5.2 kg BW) were assigned to the eight silage treatments (five
      steers per treatment) and individually fed using electronic gates. Diets
      consisted of 60% corn silage and 40% chopped alfalfa hay (DM basis). Following a
      5-d adaptation period, intake was measured for 7 d and subsequently fecal samples
      were collected for 5 d. Chromic oxide (5 g/d) was fed beginning 7 d before fecal
      sample collection and digestibility was determined by the ratio of Cr in the feed
      and feces. Steers were reallocated to treatments and these procedures were
      repeated, providing 10 observations per treatment. In addition, all silages were
      ruminally incubated in six mature cows for 0, 8, 16, 24, 48, and 96 h to
      determine extent and rate of DM, starch, NDF, and ADF disappearance. Processing
      increased DMI of hybrid 3489 but did not affect DMI of hybrid 3335 (hybrid x
      processing; P < 0.06). Total tract digestibility of DM, starch, NDF, and ADF
      decreased (P < 0.01) as plant maturity increased. Maturity tended to decrease
      starch digestibility more for hybrid 3489 than for hybrid 3335 (hybrid x
      maturity; P < 0.10). Processing increased (P < 0.01) starch digestibility but
      decreased (P < 0.01) NDF and ADF digestibility, resulting in no processing effect
      on DM digestibility. There was a numerical trend for processing to increase
      starch digestibility more for latethan for early-maturity corn silage (maturity x
      processing; P = 0.11). Processing increased in situ rates of DM and starch
      disappearance and maturity decreased in situ disappearance rates of starch and
      fiber. These data indicate that hybrid, maturity, and processing all affect corn
      silage digestibility. Mechanical processing of corn silage increased starch
      digestibility, which may have been associated with the observed decreased fiber
      digestibility.

PMID- 11583414
TI  - The effects of several supplementation frequencies on forage use and the
      performance of beef cattle consuming dormant tallgrass prairie forage.
AB  - Two experiments were conducted to quantify the impact on forage use and
      performance of varying supplementation frequency of cattle consuming forage diets
      across a range of frequencies. In both experiments, a common supplement was used
      that contained a relatively high concentration of CP (43%) and was fed at the
      following frequencies: 1) 2 d/wk; 2) 3 d/wk; 3) 5 d/wk; and 4) 7 d/wk. In Exp. 1,
      120 Hereford x Angus cows (BW = 537 kg) grazing winter tallgrass-prairie range
      were supplemented at the various frequencies from December 7 until calving
      (average calving date = 3/7/99). All treatments provided the same quantity of
      supplement on a weekly basis (12.74 kg, as-fed) but divided the amount delivered
      on a given day equally among the number of supplementation events for that
      treatment. Less BW was lost from December 7 through calving (linear effect, P =
      0.02) as frequency of supplementation increased, but the magnitude of difference
      in weight change was relatively small. Body condition responded similarly through
      early February (linear effect, P = 0.02), although treatment effects were not as
      distinct at calving (cubic effect, P = 0.11). In Exp. 2, 16 ruminally fistulated
      Hereford x Angus steers (BW = 257 kg) were blocked by weight and assigned to one
      of the four frequencies of supplementation. Steers were offered tallgrass prairie
      hay (73.5% NDF, 4.8% CP) ad libitum and were supplemented at a rate (relative to
      BW) similar to that of the cows in Exp. 1. Increasing frequency of
      supplementation increased (linear effect, P < or = 0.02) forage OM intake, OM and
      NDF digestion, and digestible OM intake. However, the most prominent differences
      in forage OM intake tended (cubic effect, P = 0.07) to occur with the two extreme
      frequencies of supplementation. In conclusion, forage use was improved with an
      increased frequency of supplementation, but the impact on performance is not
      likely to be large unless extreme differences in frequency occur.

PMID- 11583415
TI  - Direct and correlated responses to two-stage selection for ovulation rate and
      number of fully formed pigs at birth in swine.
AB  - Our objectives were to estimate responses and genetic parameters for ovulation
      rate, number of fully formed pigs at birth, and other production traits following
      two-stage selection for increased ovulation rate and number of fully formed pigs.
      Eight generations of selection were practiced in each of two lines. One selection
      line was derived from a line that previously selected eight generations for an
      index to increase ovulation rate and embryonic survival (the IOL pigs). The other
      selection line was derived from the unselected control line of the index
      selection experiment (the COL pigs). The control line (C) was continued with
      random selection. Due to previous selection, Line IOL had greater ovulation rate
      (4.24 +/- 0.38 and 4.14 +/- 0.29 ova) and litter size (1.97 +/- 0.39 and 1.06 +/-
      0.38 pigs) at Generation 0 of two-stage selection than did Lines COL and C. In
      Stage 1, all gilts from 50% of the largest litters were retained. Approximately
      50% of them were selected for ovulation rate in Stage 2. Gilts selected for
      ovulation rate were mated to boars selected from the upper one-third of the
      litters for litter size. At Generations 7 and 8, differences in mean EBV for
      ovulation rate and litter size between Lines IOL and C were 6.20 +/- 0.29 ova and
      4.66 +/- 0.38 pigs; differences between Lines COL and C were 2.26 +/- 0.29 ova
      and 2.79 +/- 0.39 pigs; and differences between Lines IOL and COL were 3.94 +/-
      0.26 ova and 1.86 +/- 0.39 pigs. Regressions of line mean EBV on generation
      number were 0.27 +/- 0.07 ova and 0.35 +/- 0.06 pigs in Line IOL; 0.30 +/- 0.06
      ova and 0.29 +/- 0.05 pigs in Line COL; and 0.01 +/- 0.07 ova and 0.02 +/- 0.05
      pigs in Line C. Correlated responses were decreased age at puberty and increased
      number of pigs born alive, number of mummified pigs, prenatal loss, and
      individual and litter birth weight. Two-stage selection for ovulation rate and
      number of pigs per litter is a promising procedure to improve litter size in
      swine.

PMID- 11583416
TI  - Survival analysis of lamb mortality in a terminal sire composite population.
AB  - Records of mortality during the first year of life of 8,642 lambs from a
      composite population at the U.S. Meat Animal Research Center were studied using
      survival and logistic analyses. The traditional logistic approach analyzes the
      binary response of whether or not a lamb survived until a particular time point,
      thus disregarding information on the actual age at death. Survival analysis
      offers an alternative way to study mortality, wherein the response variable
      studied is the precise age at death while accounting for possible record
      censoring. Lamb mortality was studied across five periods based on management
      practices: birth to weaning, birth to 120 d of age, birth to 365 d of age,
      weaning to 365 d of age, and 120 to 365 d of age. Explanatory variables included
      in the models were sex, type of birth, age of dam, and whether or not a lamb was
      raised in a nursery. The survival analysis was implemented using Weibull and Cox
      proportional hazards models with sire as random effect. The logistic approach
      evaluated sire, animal, and maternal effects models. Lambs culled during any
      period were treated as censored in the survival analyses and were assumed alive
      in the logistic analyses. Similar estimates of the explanatory variables were
      obtained from the survival and logistic analyses, but the survival analyses had
      lower standard errors than the logistic analyses, suggesting a slight superiority
      of the former approach. Heritability estimates were generally consistent across
      all periods ranging from 0.15 to 0.21 in the Weibull model, 0.12 to 0.20 in the
      Cox model, 0.08 to 0.11 in the logistic sire model, 0.04 to 0.05 in the logistic
      animal model, and 0.03 to 0.07 in the maternal effects logistic model. Maternal
      effects were important in the early stages of lamb life, but the maternal
      heritability was less than 0.07 in all the stages studied with a negative
      correlation (-0.86 to -0.61) between direct and maternal effects. The estimates
      of additive genetic variance indicate that the use of survival analysis estimates
      in breeding schemes could allow for effective selection against mortality,
      thereby improving sheep productivity, welfare, and profitability.

PMID- 11583417
TI  - Synthesis of direct and maternal genetic components of economically important
      traits from beef breed-cross evaluations.
AB  - Published information on relative performance of beef breed crosses was used to
      derive combined estimates of purebred breed values for predominant temperate beef
      breeds. The sources of information were largely from the United States, Canada,
      and New Zealand, although some European estimates were also included. Emphasis
      was on maternal traits of potential economic importance to the suckler beef
      production system, but some postweaning traits were also considered. The
      estimates were taken from comparison studies undertaken in the 1970s, 1980s and
      1990s, each with representative samples of beef breeds used in temperate
      agriculture. Weighting factors for breed-cross estimates were derived using the
      number of sires and offspring that contributed to that estimate. These weights
      were then used in a weighted multiple regression analysis to obtain single
      purebred breed effects. Both direct additive and maternal additive genetic
      effects were estimated for preweaning traits. Important genetic differences
      between the breeds were shown for many of the traits. Significant regression
      coefficients were estimated for the effect of mature weight on calving ease, both
      maternal and direct additive genetic, survival to weaning direct, and birth
      weight direct. The breeds with greater mature weight were found to have greater
      maternal genetic effects for calving ease but negative direct genetic effects on
      calving ease. A negative effect of mature weight on the direct genetic effect of
      survival to weaning was observed. A cluster analysis was done using 17 breeds for
      which information existed on nine maternal traits. Regression was used to predict
      breed-cross-specific heterosis using genetic distance. Only five traits, birth
      weight, survival to weaning, cow fertility, and preweaning and postweaning growth
      rate had enough breed-cross-specific heterosis estimates to develop a prediction
      model. The breed biological values estimated provide a basis to predict the
      biological value of crossbred suckler cows and their offspring.

PMID- 11583418
TI  - A whole-genome scan for quantitative trait loci affecting teat number in pigs.
AB  - A whole-genome scan was conducted using 132 microsatellite markers to identify
      chromosomal regions that have an effect on teat number. For this purpose, an
      experimental cross between Chinese Meishan pigs and five commercial Dutch pig
      lines was used. Linkage analyses were performed using interval mapping by
      regression under line cross models including a test for imprinting effects. The
      whole-genome scan revealed highly significant evidence for three quantitative
      trait loci (QTL) affecting teat number, of which two were imprinted. Paternally
      expressed (i.e., maternally imprinted) QTL were found on chromosomes 2 and 12. A
      Mendelian expressed QTL was found on chromosome 10. The estimated additive
      effects showed that, for the QTL on chromosomes 10 and 12, the Meishan allele had
      a positive effect on teat number, but, for the QTL on chromosome 2, the Meishan
      allele had a negative effect on teat number. This study shows that imprinting may
      play an important role in the expression of teat number.

PMID- 11583419
TI  - Shade and water misting effects on behavior, physiology, performance, and carcass
      traits of heat-stressed feedlot cattle.
AB  - One hundred twelve crossbred feedlot heifers were used in two experiments to
      assess the impact of heat stress and its relief by shade and(or) water misting on
      behavior, physiology, performance, and carcass traits. Treatments were 1) no
      shading or misting (CONT); 2) only misting (MIST); 3) only shading (SHADE); and
      4) shading plus misting (SHMI). Head in the feed bunk, head in or above the
      waterer, walking, standing, and lying behaviors were observed. Rectal
      temperature, respiration rate, and carcass traits were measured, as well as DMI,
      ADG, and feed:gain. Dietary NEm and NEg concentrations were calculated from
      performance data. In Exp. 1, (32 heifers; average BW 288 kg) the CONT heifers
      spent more time lying down than all others (P < 0.01). In addition, CONT heifers
      spent less time (P < 0.01) standing than SHADE and MIST heifers. Misting
      decreased (P < 0.01) rectal temperature and MIST as well as SHADE lowered (P <
      0.05) respiration rates. In Exp. 2 (80 heifers; average BW = 336 kg), lying and
      walking behaviors did not differ among treatments, but shade increased (P < 0.01)
      standing behavior in heifers. The MIST cattle performed less (P < 0.05) head
      above-water behavior than unmisted cattle. Rectal temperatures did not differ
      among treatments, but respiration rate was lower in shaded than in unshaded
      heifers (P < 0.05). Shaded compared with unshaded heifers had greater DMI (9.46
      vs 8.80 +/- 0.14 kg/d, P < 0.01) and ADG (1.6 vs 1.41 +/- 0.1 kg/d, P < 0.01).
      Heifers provided with shade reached their target BW 20 d earlier than the
      unshaded heifers and differed in final BW (547 vs 520 +/- 6 kg, P < 0.01).
      Feed:gain and calculated NEg and NEm concentrations did not differ among
      treatments, and carcass traits were generally similar among treatments. In
      conclusion, cattle without shade had a physiological and behavioral stress
      response to heat that negatively affected productivity. Providing shade for beef
      cattle was a suitable solution to decrease heat stress and to lower the negative
      effects of heat on performance, whereas misting was largely ineffective.

PMID- 11583420
TI  - Transcriptional regulation of fatty acid synthase gene by somatotropin in 3T3
      F442A adipocytes.
AB  - Somatotropin (ST) antagonizes insulin stimulation of fatty acid synthase (FAS)
      enzyme activity and gene transcription in adipocytes. Previous studies have shown
      that an insulin response element (IRE) is located in the proximal region of the
      FAS promoter (-71 to -50) and upstream stimulatory factor (USF) 1 binds to this
      IRE. The present study was conducted to initially evaluate whether there is a
      somatotropin response element (STRE) in the 5'flanking region of the FAS gene and
      to determine whether USF1 mediates the effect of ST on FAS gene transcription in
      3T3-F442A adipocytes. Two 5' deletion FAS promoter constructs (pFAS-CATS4 and
      pFAS-CAT5), which contain the 5' flanking sequences of the rat FAS gene at -112
      to +65 and -2195 to +65, respectively, were stably transfected into 3T3-F442A
      preadipocytes. Insulin stimulated chloramphenicol acetyltransferase (CAT)
      activity 1.7- and 4.7-fold (P < 0.05) in 3T3-F442A adipocytes transfected with
      pFAS-CATS4 and pFAS-CAT5, respectively. In contrast, bovine somatotropin (bST)
      attenuated the stimulatory effect of insulin on CAT activity by approximately 60%
      (P < 0.05) in both constructs. When 3T3-F442A adipocytes were treated with
      insulin (10 ng/mL) or insulin (10 ng/mL) plus bST (100 ng/mL) for 24, 48, or 72
      h, neither insulin nor bST significantly affected USF1 mRNA levels. When human
      USF1 (hUSF1) cDNA probe was used, however, insulin increased the abundance of an
      unidentified transcript (named hUSF1-like mRNA) 11- to 25-fold (P < 0.05) and ST
      decreased the stimulatory effect of insulin on hUSF1-like mRNA levels by 50 to
      90% (P < 0.05). Western blot analyses of nuclear extracts from cells treated with
      insulin (10 ng/mL) or insulin (10 ng/mL) plus bST (100 ng/mL) for 48 h
      demonstrated that the abundance of USF1 was not affected by insulin or ST.
      Furthermore, electrophoretic mobility shift analyses (EMSA) of nuclear extracts
      revealed that neither insulin nor ST had an effect on the binding of USF1 to the
      IRE. These results suggest that a STRE may be located within the first 112 bp of
      the FAS promoter and that USF1 does not directly mediate the effect of ST on
      transcription of the FAS gene in 3T3-F442A adipocytes.

PMID- 11583421
TI  - Vitamin-mineral supplementation and accelerated chilling effects on quality of
      pork from pigs that are monomutant or noncarriers of the halothane gene.
AB  - We examined the effects of vitamin and mineral supplementation of the finishing
      diet on growth and accelerated chilling of carcasses on carcass and muscle traits
      of halothane gene carrier and noncarrier pigs. Barrows and gilts that were either
      monomutants (MON, n = 49) or noncarriers (NON, n = 28) of the halothane gene were
      fed a standard finishing diet until they reached 86 kg. They then were randomly
      assigned to one of four finishing diets formulated to contain 11 IU/kg vitamin E
      (0), 311 IU/kg vitamin E plus additional vitamins and minerals (300), 611 IU/kg
      vitamin E plus additional vitamins and minerals (600), or 911 IU/kg vitamin E
      plus additional vitamins and minerals (900) until they were slaughtered (118 kg).
      Alternating carcass sides were assigned either a normal chilling procedure (NC, 4
      degrees C for 24 h) or an accelerated chilling procedure (AC, -20 degrees C for
      1.5 h and then 4 degrees C for 22.5 h). Supplementing vitamin E in the finishing
      diet increased (P < 0.05) the concentration of vitamin E in the longissimus
      muscle. Supplementing vitamin E in the diets of MON pigs did not affect color,
      firmness, or cooking losses of loins or color and firmness of hams. For the NON
      genotype, increasing the level of vitamin E in the diet decreased (P < 0.05) the
      percentage of PSE loins and hams. Color and firmness scores of the gluteus medius
      and longissimus muscles were improved 0.4 unit (P < 0.005) by AC compared with NC
      of carcasses. Loin chop juiciness and flavor were improved (P < 0.05) in the MON
      genotype for AC compared to NC. Accelerated chilling reduced (P < 0.05) the
      percentage of PSE loins from 38 to 17% and PSE hams from 32 to 10% for the MON
      genotype, but percentage of PSE was not affected (P > 0.05) by chilling treatment
      for the NON genotype. No interaction between diet and chill treatments existed
      for muscle quality traits (P > 0.05). Supplementing finishing diets of NON pigs
      with at least 600 IU/kg vitamin E, in addition to other vitamins and minerals, or
      accelerated chilling of MON carcasses can reduce the incidence of PSE pork.

PMID- 11583422
TI  - Dynamic ideal protein and limiting amino acids for lactating sows: the impact of
      amino acid mobilization.
AB  - The limiting amino acids for lactating sows were determined using 28 primiparous
      sows that were intentionally underfed both energy and protein during a 21-d
      lactation. Groups of four sows were allotted to litter-size treatments of 6, 7,
      8, 9, 10, 11, or 12 by cross-fostering as needed within 48 h postpartum. Sows
      were killed on d 21 of lactation. The carcass, liver, gastrointestinal tract,
      reproductive tract, mammary gland, and other viscera were separated, weighed,
      ground, and analyzed for dry matter, crude protein, and amino acids. Simple
      linear equations were obtained for each amino acid within tissues as a function
      of litter size. The mobilization of amino acids from carcass, liver,
      gastrointestinal tract, reproductive tract, and other viscera increased as litter
      size increased. Amino acids were accreted to mammary glands as litter size
      increased (2.65 g lysine/21 d for each one-pig increase in litter size). Milk
      production needs were estimated (49.9 g lysine/21 d for each one-pig increase in
      litter size). The quantity of each amino acid required additionally as litter
      size increased was obtained from the difference between amino acid needs for milk
      production and mammary gland growth and those provided from tissue mobilization.
      The relative ratio among amino acids that are required additionally (ideal amino
      acid pattern) was compared with the relative ratio of amino acids that can be
      provided from a corn-soybean meal lactation diet. From the comparison, it was
      shown that threonine and lysine are the first-limiting amino acids, followed by
      valine, when tissue mobilization occurs during lactation. Lysine is the first
      limiting amino acid, and valine becomes second-limiting followed by threonine,
      when sows do not mobilize body tissues during lactation. Thus, the limiting order
      of essential amino acids changes depending on feed intake and tissue mobilization
      of sows during lactation. Proper feeding of lactating sows should consider the
      expected degree of tissue mobilization during lactation.

PMID- 11583423
TI  - Effect of energy and lysine intake in gestation on sow performance.
AB  - Nutrient intake during gestation has an impact on gestation parameters and
      subsequent lactation performance. The objectives of this experiment were to
      determine the impact of feeding two levels of amino acids in gestation on sow BW
      changes in gestation and lactation, and litter size, and to evaluate a factorial
      method for determining daily energy requirements. At mating, 419 sows (Camborough
      15; Pig Improvement Canada, Acme, AB) were assigned randomly within Parities 1, 2
      or 3+ to a gestation diet containing either 0.44% (low lysine) or 0.55% (high
      lysine) total lysine and 3,100 kcal DE/kg; other indispensable amino acids were
      adjusted to lysine based on ideal protein ratios. Feed allowance in gestation was
      determined factorially using estimated DE requirements for maintenance, maternal
      gain, and conceptus growth. Sows were allowed free access to the lactation diet.
      Gestation BW gain from d 0 to 110 was affected by parity (61.2, 60.0, and 42.3 kg
      for Parity 1, 2, and 3+, respectively; P < 0.05) but not (P > 0.10) by gestation
      lysine level. Sow BW changes from d 0 of lactation to weaning were affected by
      parity (0.5, 6.8, and 5.8 kg for Parity 1, 2, and 3+, respectively; P < 0.01) and
      gestation BW gain (P < 0.01), but not by gestation lysine level (5.0 vs 3.8 kg
      for low and high lysine, respectively; P > 0.10). Total piglets born was affected
      by parity (11.5, 12.1, and 12.5, for Parity 1, 2, and 3+, respectively; P < 0.01)
      and increased with increasing sow BW gain (P < 0.05). Total piglets born alive
      (mean = 11.2) was increased with increasing sow BW gain (P < 0.05). Total litter
      weight born alive was affected by parity (15.9, 18.6, and 19.4 kg for Parities 1,
      2, and 3+, respectively; P < 0.01) and gestation BW gain (P < 0.05). The model
      used to determine daily energy intake requirements resulted in an average BW gain
      of 10.6 kg above the targets set by the model. Total lysine intakes greater than
      10.6 g/d in gestation did not improve sow productivity. Setting target weight
      gains in gestation and feeding to meet these targets may not always provide
      predictable results due to a number of factors that affect the energy requirement
      in the sow.

PMID- 11583424
TI  - Effect of nutrient intake in lactation on sow performance: determining the
      threonine requirement of the high-producing lactating sow.
AB  - Reproductive performance is steadily increasing within the pork industry;
      logically, amino acid requirements need to be redefined for sows producing larger
      litters. The objective of this study was to determine the threonine requirement
      of the high-producing lactating sow and to determine the effect of lysine on this
      requirement. A total of 419 PIC C-15 sows were assigned randomly to treatment
      within parity groups (1, 2, and 3+) and gestation treatment at d 110 of
      gestation. Lactation diets were formulated to contain 0.80% total lysine (tLYS)
      with 0.30, 0.35, 0.40, 0.45, 0.50, 0.55, 0.60, or 0.65% total threonine (tTHR) or
      1.06% tLYS with 0.40, 0.45, 0.50, 0.55, 0.60, 0.65, or 0.70% tTHR. Litters were
      standardized to a minimum of 11 piglets within 48 h after farrowing, and sows had
      free access to feed throughout lactation (lactation length = 20.1 +/- 0.1 d). Sow
      ADFI exceeded expectation, averaging 6.90, 7.40, and 7.20 kg/d for Parities 1, 2,
      and 3+, respectively. Daily tLYS intake was 58 g/d (47 g of apparent ileal
      digestible lysine [dLYS] per day) and 74 g/d (59 g dLYS/d) for the low- and high
      lysine group, respectively. Lysine intake did not affect sow or litter
      performance (P > 0.10). Sows gained an average of 4.8 kg in lactation. Using
      regression analysis, BW gain was maximized at 0.54% tTHR for all parity groups
      (quadratic; P < 0.05). Litter weaning weight (67.1, 67.9, and 66.2 kg for
      Parities 1, 2, and 3+, respectively) and litter weight gain (2.49, 2.53, and 2.44
      kg/d for Parities 1, 2, and 3+, respectively) were maximized at 0.53% tTHR using
      regression analysis, for all parity groups (quadratic; P < 0.05). Based on
      regression analysis, plasma urea nitrogen on d 10 and 18 was minimized at 0.54%
      tTHR (P < 0.05). Lysine levels in excess of 58 g of tLYS/d did not benefit sow or
      litter performance. The requirement for threonine to minimize sow tissue
      mobilization was 37, 40, and 38 g tTHR/d (28, 30, and 30 g of apparent ileal
      digestible threonine [dTHR] per day) for Parities 1, 2, and 3+ sows,
      respectively. The threonine required to maximize litter performance was 36, 39,
      and 38 g of tTHR/d (28, 30, and 29 g of dTHR/d) for Parities 1, 2, and 3+ sows,
      respectively. Alternatively, the requirement can be expressed as 14.3 g tTHR
      (11.8 g dTHR) per kilogram of litter gain.

PMID- 11583425
TI  - Ileal digestibilities of neutral detergent fiber, crude protein, and amino acids
      associated with neutral detergent fiber in wheat shorts for growing pigs.
AB  - An experiment was carried out to determine the ileal digestibility values of NDF,
      CP, and AA associated with NDF in different samples of wheat shorts consisting of
      different proportions of wheat bran, shorts, and flour, hereafter referred to as
      wheat fractions. Six barrows (average initial BW 37.2 kg, and fitted with a
      simple T-cannula at the distal ileum) were fed one of six experimental diets,
      formulated to contain 17% CP (as-fed basis), according to a 6 x 6 Latin square
      design. Diets A, B, C, D, and E contained 17.53% soybean meal (SBM), which
      contributed 50% CP to these diets. The diets contained shorts, bran, or flour
      alone or in combination, contributing the remaining 50% CP to these diets. The
      proportions of shorts, bran, and flour in the wheat fractions were 70% shorts and
      30% bran in diet A, 85% shorts and 15% bran in diet B, 100% shorts in diet C, 85%
      shorts and 15% flour in diet D, and 70% shorts and 30% flour in diet E. Diet F
      contained 35.05% soybean meal, which provided the sole source of dietary CP.
      Chromic oxide was used as a digestibility marker. During the first experimental
      period, the daily dietary allowance was provided at a rate of 5% (wt/wt) of the
      average BW. Thereafter, the allowance was increased by 100 g at each successive
      period. Each experimental period comprised 12 d. Following a 7-d adaptation
      period, feces were collected for 48 h and ileal digesta for a total of 24 h. The
      contribution of CP and AA associated with NDF gradually decreased from wheat
      fraction A to E, reflecting a decrease in NDF content from 42.3 to 29.5%. Of the
      indispensable AA in wheat fraction A, the contributions ranged from 12.9 to
      15.9%. In wheat fraction E, these values ranged from 9.0 to 11.3%. The ileal
      digestibility values of NDF ranged from 11.8% in diet E to 17.1% in diet C (P >
      0.05). There were usually no differences (P > 0.05) in the ileal digestibilities
      of AA associated with NDF between the wheat fractions. However, with the
      exception of lysine and tyrosine, there were negative correlations (P < 0.05)
      between the apparent ileal AA digestibilities and the content (%) of CP
      associated with NDF in the wheat fractions. Furthermore, there was no effect (P >
      0.05) of the diets containing wheat fractions on the recovery of bacterial
      protein and mucin in ileal digesta.

PMID- 11583426
TI  - The influence of gestation feeding strategy on body composition of gilts at
      farrowing and response to dietary protein in a modified lactation.
AB  - Previous experiments have indicated that reproductive function in lean, modern
      genotypes may be more dependent on body protein mass than, as previously
      believed, on body lipid reserves. This was investigated in a 3 x 2 factorial
      arrangement of treatments, involving 60 first-parity sows, comparing three
      pregnancy feeding strategies and two lactation diets. During pregnancy, sows were
      fed either a basal diet (5 g lysine/kg, 13 MJ of DE/kg [C]) or the same quantity
      of basal diet + energy source [E], or additional basal diet supplying both
      protein and energy [A]. The level of supplement for E and A was adjusted weekly
      to achieve a backfat thickness measurement (P2 position) of 28 mm at farrowing.
      Isoenergetic lactation diets were fed to appetite and provided either high (180 g
      CP/kg, 9 g lysine/kg [H]) or low lysine (120 g CP/kg, 6 g lysine/kg [L]). From d
      21 of lactation, sows were separated from their litters and housed next to a boar
      for 8 h each day; final weaning occurred on d 31. Pregnancy treatment differences
      in backfat and weight were achieved, with C sows having less backfat on d 1 of
      lactation than E and A sows (E = 28.1, A = 28.0, C = 22.7 kg, P < 0.001). Sows
      fed additional basal diet were heavier than E sows, which were heavier than C
      sows (E = 190, A = 201, C = 178 kg, P < 0.001). Average feed intake over
      lactation showed a pregnancy feeding effect, with E sows eating less than A or C
      sows (E = 4.9, A = 5.2, C = 5.4 kg/d, P < 0.005). Total lactation weight loss was
      affected by pregnancy feeding (E = 18.0, A = 19.0, C = 8.4 kg, P < 0.05) and by
      lactation diet (L = 19.0, H = 11.3 kg, P < 0.05), whereas total lactation backfat
      loss was affected only by pregnancy treatment (E = 6.9, A = 6.5, C = 4.6 mm, P <
      0.05). No pregnancy treatment or lactation diet effects were observed for litter
      performance. Lactation diet affected weaning-to-estrus interval, with more sows
      on the H diet coming into estrus within 6 d of partial weaning (P < 0.05), but
      there was no pregnancy treatment effect. Therefore, voluntary feed intake during
      lactation was suppressed by increased fat reserves at a limited body protein mass
      but not when body protein mass was also increased. Partial weaning-to-estrus
      interval was increased by reduced dietary protein.

PMID- 11583427
TI  - Adipic acid increases plasma lysine but does not improve the efficiency of lysine
      utilization in swine.
AB  - Adipic acid, upon catabolism, results in intermediates that bear a structural
      similarity to lysine degradation products. The objectives of this research were
      to determine whether adipic acid affects lysine concentrations in plasma and to
      evaluate whether adipic acid improves the efficiency of lysine utilization in
      pigs. In Exp. 1, nursery pigs (n = 14) were fed (for a period of 7 d) either a
      standard nursery diet or the same diet supplemented with 1% adipic acid to assess
      effects on plasma amino acid concentrations (plasma collected on d 7). In Exp. 2,
      nursery pigs (n = 56) were fed (for a period of 15 d) either a control diet or
      the same diet but deficient in either lysine, threonine, or tryptophan with or
      without supplemental adipic acid to assess the effects of adipic acid on the
      efficiency of amino acid utilization. The results from Exp. 1 showed that adipic
      acid increased plasma lysine (by 18%) but not alpha-amino adipic acid, an
      intermediate in lysine degradation. Experiment 2 demonstrated that adipic acid
      did not increase the efficiency of utilization of lysine, threonine, or
      tryptophan. The lack of effects on alpha-amino adipic acid in Exp. 1 and the lack
      of a positive effect on the efficiency of utilization of lysine, threonine, and
      tryptophan suggest that adipic acid does not inhibit the mitochondrial uptake of
      lysine and(or) its degradation in the mitochondrion. It is concluded that feeding
      adipic acid increases plasma lysine but does not improve the efficiency of lysine
      utilization.

PMID- 11583428
TI  - Dietary adipic acid reduces ammonia emission from swine excreta.
AB  - Adipic acid is only partially catabolized when it is fed to animals, and a
      portion of it is excreted in urine. The excreted portion may lower urinary pH
      and, as a result, ammonia emission. The present study tested this hypothesis. In
      Exp. 1, nursery pigs (n = 14) were fed (for a period of 7 d) either a standard
      nursery diet or the same diet supplemented with 1% adipic acid to assess effects
      on urinary pH (collected on d 5 or 6) and in vitro ammonia emission from the
      collected urine samples that were mixed with control feces. In Exp. 2, grower
      pigs housed 10 each in one of two chambers were fed a control diet or the same
      diet supplemented with 1% adipic acid. Ventilated air was quantified and analyzed
      for ammonia using Fourier transform infrared spectroscopy to determine the
      effects of feeding 1% adipic acid on ammonia emission. The results from Exp. 1
      showed that adipic acid strongly reduced urinary pH (from 7.7 to 5.5, P < 0.05).
      In vitro ammonia emission from these urine samples was significantly reduced at
      all the time points evaluated (1, 3, 18, and 46 h with reductions of 94, 93, 70,
      and 39%, respectively, P < 0.05). Experiment 2 showed that adipic acid
      supplementation reduced ammonia emission by 25% (P < 0.05), which corresponded to
      the predicted reduction in ammonia emission based on the reduction in manure pH
      observed. In conclusion, feeding adipic acid lowers urinary pH and reduces
      ammonia emission. The reduction in ammonia emission, though, does not correspond
      to the reduction in urinary pH but corresponds to the reduction in fecal pH as a
      result of mixing the urine and feces, in which feces act as a strong buffer.

PMID- 11583429
TI  - Comparative total tract digestibility of dietary energy and nutrients in growing
      pigs and adult sows.
AB  - Seventy-seven diets were fed to 61-kg growing pigs at a feeding level close to
      their ad libitum intake and to nonlactating, nonpregnant sows slightly above
      their maintenance energy level (2.4 kg/d). The main objectives of this study were
      to compare the total tract digestibility of dietary energy or nutrients of the 77
      diets in growing pigs and adult sows and to analyze the effect of diet chemical
      composition on total tract digestibility in both groups of pigs. Diets were
      formulated to represent a range of chemical compositions as large as those found
      in most practical situations. The DE and ME values and total tract digestible
      nutrient contents of diets were measured for each group of animals; each diet was
      measured in four to five animals per group, and collection of urine and feces
      lasted 10 d. The results were used to establish equations for predicting DE and
      ME values, total tract digestible nutrient contents, and total tract
      digestibility coefficients of energy from chemical characteristics for each group
      of animals. The results show that the total tract digestibility of energy or
      nutrients was higher (P < 0.01) in adult sows than in growing pigs; the total
      tract digestibility coefficients of energy, crude protein, ether extract, and NDF
      averaged 85.2, 85.1, 37.1, and 64.4%, respectively, for sows and 82.1, 80.3,
      31.6, and 56.3%, respectively, for growing pigs. The ME/DE ratio was lower (P <
      0.01) in sows (94.8%) than in growing pigs (96.5%), as a result of higher urinary
      energy losses in sows. The difference in DE values (on average, 0.6 MJ/kg of DM)
      between adult sows and growing pigs was not constant (P < 0.01) but increased
      with dietary fiber content (3.3, 8.6, and 10.1 kJ for each gram of NDF, ADF, and
      crude fiber increase in the diet, respectively), which suggests that the origin
      of the difference between the two physiological stages is mainly due to a higher
      rate of degradation of dietary fiber in the hindgut of sows. The DE and ME values
      could be accurately predicted from total tract digestible nutrients or from
      chemical characteristics for each physiological stage. Equations for predicting
      urinary energy loss from urinary N are also proposed. From a practical point of
      view, it is suggested to use two energy values for pig feeds: one applicable to
      growing-finishing pigs and one to adult sows. Equations for predicting DE in
      adult sows from energy values obtained in growing pigs are proposed.

PMID- 11583430
TI  - Effect of different protein sources on growth and carcass traits in growing
      finishing pigs.
AB  - Crossbred gilts (n = 180) and barrows (n = 180) from the Louisiana State
      University (LSU) Agricultural Center and the University of Illinois (UI) were
      used to compare the effect of soybean meal in swine diets, relative to other
      protein sources, on growth performance and carcass traits of growing-finishing
      pigs. Four replications with five pigs each at each location were allotted to
      nine dietary treatments: soybean meal control (SBM), crystalline AA (corn-AA),
      extruded soybeans (ESB), canola meal (CAN), peanut meal (PNT), sunflower meal
      (SFLR), ground peas, meat and bone meal (MBM), and poultry by-product meal
      (PLTY). The diets were formulated to meet or exceed NRC nutrient requirements and
      to have equal Lys:ME according to dietary phase and sex. Corn was the grain
      source in all diets and the protein sources were the sole source of supplemental
      protein in all diets except when AA were added to meet the requirement. Pigs
      (three per pen at each location) were killed at an average final BW of 114 kg in
      the LSU or UI Meat Science Laboratories. Pigs fed SBM had greater (P < 0.05) ADG
      than pigs fed the corn-AA, CAN, SFLR, MBM, or PLTY and greater (P < 0.05) ADFI
      relative to pigs fed the corn-AA, ESB, MBM, or PLTY. Gain:feed was decreased (P <
      0.05) in pigs fed corn-AA or SFLR but increased (P < 0.05) in pigs fed ESB
      compared with pigs fed the SBM diet. Loin muscle area was decreased (P < 0.05) in
      pigs fed the corn-AA or MBM diets compared with pigs fed the SBM diet. Tenth-rib
      backfat thickness was greater (P < 0.10) in pigs fed corn-AA, peas, or MBM than
      in those fed SBM. The NPPC percentage acceptable quality lean and kilograms of
      lean were decreased (P < 0.10) in pigs fed corn-AA, peas, or MBM compared with
      those fed SBM. Results from this experiment suggest that pigs fed SBM have equal
      or better growth performance and carcass traits than pigs fed other protein
      sources.

PMID- 11583431
TI  - Technical note: Vitrification of goat embryos by the open pulled-straw method.
AB  - The suitability of the open pulled-straw (OPS) method for vitrifying bovine
      embryos was tested for goat embryos. Of 14 does receiving OPS-vitrified embryos,
      all became pregnant and 13 (93%) kidded. The corresponding values for an
      established conventional freezing program were 58% pregnant and 50% (6/12)
      kidding. Overall embryo survival amounted to 64% (18/28) for OPS-vitrified and
      42% (10/24) for conventionally frozen embryos. All differences were statistically
      significant. It is concluded that OPS vitrification is a suitable method for
      cryopreserving caprine d-7 blastocysts.

PMID- 11583432
TI  - Effects of nitrogen fertilization and harvest date on yield, digestibility,
      fiber, and protein fractions of tropical grasses.
AB  - To evaluate the response of three tropical forage species to varying rates of
      nitrogen (N) fertilization [0, 39, 78, 118, 157 kg of N/(ha x cutting)] and five
      summer harvests, forage DM mass and nutritive value were evaluated in a
      randomized complete block design with a split-split plot arrangement of
      treatments. Plots (n = 60) were established in 1996, and five harvests were
      conducted every 28 d from June through September in 1997 and 1998, with
      fertilizer applications occuring after each harvest. Fertilization with 78 kg of
      N/(ha x cutting) increased forage mass in these grasses by 129% (P < 0.01)
      compared with no N fertilization. Additional N did not result in further
      increases of forage mass. Bermudagrass (Cynodon dactylon) produced more forage DM
      [P < 0.01; 1,536 +/- 43 kg/(ha x cutting)] than stargrass [Cynodon nlemfuensis;
      1,403 +/- 43 kg/(ha x cutting)] or bahiagrass [Paspalum notatum; 1,297 +/- 43
      kg/(ha x cutting)]. Peak forage mass for all species occurred in late June and
      July. In vitro organic matter digestibility (IVOMD) of stargrass increased (P <
      0.01) linearly with fertilization. A quadratic response to N fertilization (P <
      0.01) was noted in IVOMD of bermudagrass, whereas bahiagrass was not affected.
      Bermudagrass was more (P < 0.01) digestible (57.5 +/- 0.4) than stargrass (54.6
      +/- 0.4) and bahiagrass (51.9 +/- 0.4%). As fertilization level increased, NDF
      decreased linearly (P < 0.01) in all three forages. Total N concentration
      increased (P < 0.01) linearly as N fertilization increased in all forages. Total
      N concentration was highest (P < 0.01) in stargrass (2.4%, DM basis) compared
      with bermudagrass (2.2%) and bahiagrass (2.0%). Total N concentration was
      depressed in all forages for late June and July harvests (P < 0.01).
      Fertilization increased (P < 0.05) the concentration (% of DM) of all protein
      fractions. In July and August, nonprotein N was reduced 11.8% (P < 0.01), whereas
      ADIN increased in July (P < 0.01). Bahiagrass had less N in cell contents than
      did bermudagrass and stargrass but had a greater concentration of N associated
      with the cell wall. Managerial factors, including rates of N fertilization and
      harvest dates, can have profound effects on the nutritional value of forage. An
      increased understanding of these effects is imperative to improve supplementation
      programs for ruminants.

PMID- 11583433
TI  - Crude protein fractions in common vetch (Vicia sativa L.) fresh forage during pod
      filling.
AB  - Crude protein (CP) of forages can be separated into fractions of differentiated
      abilities to provide available amino acids in the lower gut of ruminants. This
      knowledge is critical to develop feeding systems and to predict animal responses.
      We have measured during two growing seasons (1996 to 1997 and 1997 to 1998) the
      CP fractions of common vetch fresh forage with the objective being to assess the
      influence of maturity on concentration of CP fractions (as a percentage of total
      CP) and fraction yields. Fraction B2, which represents true protein of
      intermediate ruminal degradation rate, was the largest single fraction in common
      vetch forage (about 40% of CP across seasons and maturity stages). Soluble
      fractions (A plus B1) were less than 50% of total CP while the unavailable
      fraction C ranged from 4 to 8% of total CP. As a result, the remaining fraction
      B3 (true protein of very low degradation rate) only represented 2 to 9% of total
      CP. Concentration and yield of fraction B3 increased (P < 0.05) from flowering to
      pod-filling. Results showed that undegraded dietary protein represented a small
      proportion of total CP in common vetch forage. Moving the harvesting stage from
      flowering to the pod filling phase allowed for greater yield of undegraded
      dietary protein.

PMID- 11583434
TI  - Pasture management effects on diet composition and cattle performance on
      continuously stocked rhizoma peanut-mixed grass swards.
AB  - In Florida, rhizoma peanut (RP; Arachis glabrata Benth.), a tropical legume,
      combines the attributes of excellent nutritive value, competitive ability with
      tropical grasses, and high animal performance. The objective of this study was to
      determine the effects of spring N fertilization (0 vs 35 kg/ha) and summer
      stocking rate (1.5 and 2.5 bulls/ha) on herbage mass, nutritive value, herbage
      allowance, and diet botanical composition of grazed RP-grass swards and their
      interaction with growth and development of bulls (Senepol, and Brahman or Angus).
      The study was conducted in 1995 and 1996 at the USDA, ARS, Subtropical
      Agriculture Research Station in Brooksville, FL. Nitrogen was applied in April of
      each year, and all pastures were stocked with 1.5 bulls/ha until approximately
      July of each year, when stocking rate was increased on half the pastures to 2.5
      bulls/ha. Herbage mass (HM, kg/ha), herbage allowance (HA, kg/kg BW), nutritive
      value (CP and in vitro organic matter digestibility [IVOMD]), and diet botanical
      composition (fecal microhistological) readings were determined. Animal
      measurements included total and seasonal (spring vs summer), ADG, hip height
      (cm), scrotal circumference (SC, cm), and plasma urea nitrogen (PUN, mg/dL).
      Herbage mass (3.0 +/- 0.12 Mg/ha and 3.4 +/- 0.13 Mg/ha in 1995 and 1996,
      respectively) was not affected by nitrogen fertilization or stocking rate but was
      affected by season (P < 0.05) due to increased plant growth rate associated with
      summer rainfall. Stocking rate did affect herbage availability, but it never fell
      below 3 kg/kg BW, indicating herbage availability was never limiting. Crude
      protein (200 to 140 g/kg) and IVOMD (650 to 540 g/kg) were not affected by
      treatment, but declined (P < 0.001) from spring until fall. Treatments also had
      no effect on diet botanical composition. Summer ADG averaged about 0.2 kg/d lower
      than spring ADG, due, in part, to seasonal declines in nutritive value. Because
      herbage allowance was never limiting, full-season ADG was not affected by
      stocking rate or N fertilization and averaged 0.61 +/- 0.03 and 0.60 +/- 0.02
      kg/d in 1995 and 1996, respectively. There were season x breed interactions (P <
      0.05) for ADG due to greater declines during the summer for Angus than for
      Senepol or Brahman. There were no differences in final BW, SC, BCS, hip height,
      or PUN due to treatments, but breed differences were noted (P < 0.05) for all
      measures except BCS.

PMID- 11583435
TI  - In vitro growth and starch digestion by Entodinium exiguum as influenced by the
      presence or absence of live bacteria.
AB  - In a preliminary study, the addition of antibiotics was shown to reduce bacterial
      concentrations in Entodinium exiguum cultures by more than 99% in 4 h, whereas
      the protozoal population was apparently unaffected. Using this procedure, the
      growth and amylolytic capability of Entodinium exiguum, in the presence or
      absence of live bacteria, was studied in vitro. Treatments for Trial 1 were
      protozoa plus antibiotics (PA), PA plus autoclaved bacteria (PAB), protozoa plus
      living bacteria (PLB), and only bacteria (BAC). Autoclaved or non-autoclaved
      cornstarch was used as an energy source. Treatment main effects were as follows:
      higher concentration of E. exiguum in PLB than in PA or PAB at 24 and 48 h (P <
      0.01); PA and PAB were not different (P > 0.05); concentrations of E. exiguum
      higher in autoclaved cornstarch at 12 h (P < 0.05) but lower than in non
      autoclaved cornstarch at 24 and 48 h (P < 0.01); and starch digestion in PLB was
      higher than in PA and PAB at all time periods, but only greater than BAC up to 24
      h (P < 0.01). In Trial 2, only treatments PA, PLB, and BAC were tested. Rice
      starch and cornstarch were used as substrates. With rice starch, growth was
      higher in PLB than in PA at 24 and 48 h (P < 0.05). Starch digestion started
      earlier in PLB with rice starch (P < 0.05) but was complete for both substrates
      after 24 h. Up to 12 h (autoclaved cornstarch and rice starch) and 24 h (non
      autoclaved cornstarch and cornstarch), the sum of digestion by bacteria and
      protozoa did not equal the extent of digestion in PLB, suggesting some kind of
      synergism. Total extent of digestion with protozoa was similar between the two
      sources; however, bacteria digested rice starch faster and to a greater extent
      than cornstarch. Approximate lag times with rice starch, autoclaved cornstarch,
      and non-autoclaved cornstarch were 6, 3, and 12 h for bacteria and < 6, 3, and 9
      h for protozoa, respectively. Rate of digestion for non-autoclaved cornstarch was
      similar for bacteria and protozoa, whereas the rate of bacterial digestion was
      much faster with the other two substrates (autoclaved cornstarch and rice
      starch).

PMID- 11583436
TI  - Impact of different wheat milling by-products in supplements on the forage use
      and performance of beef cattle consuming low-quality, tallgrass-prairie forage.
AB  - Two experiments were conducted to evaluate the impacts on forage use and beef
      cattle performance of incorporating divergent wheat milling by-products in a 30%
      CP supplement. The by-products were wheat bran (high fiber) and second clears
      (high starch). The by-products were added as 1) 100% wheat bran; 2) 67% wheat
      bran, 33% second clears; or 3) 33% wheat bran, 67% second clears to constitute
      approximately 47 to 49% of the supplement. In Exp. 1, 90 Hereford x Angus cows
      (BW = 554 kg) grazing winter, tallgrass-prairie range were fed the supplement
      treatments (2.27 kg/cow daily) from early December 1997 until calving (average
      calving date = 3/11/98). Cumulative BW and condition changes from trial
      initiation through calving were not significantly different among treatments.
      Similarly, significant treatment effects on cow pregnancy rates as well as calf
      birth weights, ADG, and ending weights were not evident. In Exp. 2, 16 ruminally
      fistulated Hereford x Angus steers (BW = 484 kg) were blocked by weight and
      assigned to one of the same three supplement treatments or to a negative control
      (forage only). Steers had ad libitum access to tallgrass-prairie hay (76.4% NDF,
      3.1% CP) and were fed supplement at the same rate (relative to BW) as the cows in
      Exp. 1. Forage OM, NDF, and digestible OM intakes were lower (P < 0.01) for the
      negative control than for supplemented steers but were not significantly
      different among the supplemented steers. Digestion of OM was lower (P = 0.03) for
      the negative control than for supplemented steers, although significant treatment
      differences were not evident among the supplemented groups. Digestion of NDF was
      not affected (P = 0.49) by treatment. Within the context of the amount of
      supplemental protein offered, changes in the combination of wheat milling by
      products in the supplement did not affect cow performance or intake and digestion
      of low-quality forage.

PMID- 11583437
TI  - Influence of pregnancy on body weight, ruminal characteristics, and visceral
      organ mass in beef heifers.
AB  - Crossbred heifers (initially 24 mo, approximate age and 378 +/- 32.1 kg BW) were
      used to evaluate the influence of pregnancy and advancing gestation on DMI, BW,
      carcass weight, ruminal characteristics, and visceral organ mass. Heifers
      (naturally serviced (n = 22; nonpregnant controls, n = 17), were grouped in
      common pens. Heifers were provided corn silage and hay-based diets formulated to
      provide 0.45 kg of ADG. Treatments were pregnancy and nonpregnancy; pregnant and
      nonpregnant heifers were slaughtered on d 40, 120, 200, and 270. Live weight at
      slaughter and BW change throughout the trial were not influenced by pregnancy (P
      > 0.1). Carcass weight per unit of BW was decreased due to pregnancy (P < 0.05)
      and an interaction was found in eviscerated BW (EvBW; P < 0.1), with the pregnant
      heifers having greater live weights, carcass weights, and EvBW at the d-200
      slaughter period. Ruminal fluid fill and total fill (g/kg BW) declined as
      slaughter period advanced, resulting in the pregnant heifers having less fill at
      d 270 (P< 0.07). However, ME intake was not different between pregnant and
      nonpregnant heifers (P > 0.1) at any of the slaughter periods. Heart mass
      responded differently when nonpregnant and pregnant were analyzed over time and
      an interaction was detected as slaughter period advanced (P < 0.1). Liver,
      duodenum, jejunum, and large intestinal mass were not responsive to pregnancy (P
      > 0.1). Data indicate that ruminal fill is altered by pregnancy but visceral
      organ mass is not greatly changed by treatment.

PMID- 11583438
TI  - Rumen microbial sequestration of [2-(13)C]acetate in cattle.
AB  - To investigate the impact of rumen microbial sequestration of VFA carbon on
      estimates of acetate availability based on intraruminal infusion of [2-(13)C]
      acetate, three nonlactating or low-yielding dairy cows were continuously
      intraruminally infused with [2-(13)C]acetate for 26 h. The 13C content of ruminal
      VFA, duodenal carbon, and fatty acids (FA) and AA isolated from liquid-associated
      ruminal microbes and duodenal DM was measured by an isotope ratio mass
      spectrometer interfaced to an elemental analyzer or a gas-liquid chromatograph.
      The ruminal gross production of acetate was 38 +/- 4 mol/d and could account for
      about 38% of the DE intake. Of the intraruminally infused 13C in [2
      (13)C]acetate, 7.6 +/- 0.9% was recovered at the duodenum. The 13C content of
      ruminal propionate, butyrate, and valerate increased (P < 0.05) with intraruminal
      infusion of [2-(13)C]acetate. It was estimated that about 28% of the 13C
      intraruminally infused in [2-(13)C]acetate could be accounted for by duodenal 13C
      flow and absorption of non-acetate VFA. A number of FA isolated from liquid
      associated ruminal microbes (C6, C12, C14, anteiso C15, and iso C15) were
      enriched with 13C (P < 0.05) at a level comparable to the enrichment of ruminal
      butyrate. Any absorption of these FA from the rumen would further contribute to
      non-acetate 13C uptake. A maximum of 72% of the ruminal gross production of
      acetate represented acetate absorption from the rumen in the present study.
      Consequently, previously used models using intraruminal isotope dilution
      techniques seem not to be appropriate for measuring acetate availability in
      ruminants. The number of metabolites exchanging carbon with acetate was found to
      be so high that assessments of the entire range of inter conversions seem to be
      practically impossible. Portal absorption studies are discussed as an alternative
      method of estimating VFA availability to the metabolism in ruminants.

PMID- 11583439
TI  - Present use of pesticides for vector and allergen control and future
      requirements.

PMID- 11583440
TI  - Breeding of Anopheles mosquitoes in irrigated areas of South Punjab, Pakistan.
AB  - As part of investigations on potential linkages between irrigation and malaria
      transmission, all surface water bodies in and around three villages along an
      irrigation distributary in South Punjab, Pakistan, were surveyed for anopheline
      mosquito larvae (Diptera: Culicidae) from April 1999 to March 2000. Samples were
      characterized according to exposure to sunlight, substratum, presence of
      vegetation, fauna, inorganic matter and physical water condition
      (clear/turbid/foul). Also water temperature, dissolved oxygen (DO),
      electroconductivity (EC) and pH of sites were recorded. A total of 37982
      Anopheles larvae of six morphological types were collected from 2992 samples
      taken from irrigation/agricultural and village/domestic aquatic habitats.
      Anopheles subpictus Grassi sensu lato was by far the most abundant (74.3%),
      followed by An. culicifacies Giles s.l. (4.1%), An. stephensi Liston s.l. (2.6%),
      An. pulcherrimus Theobald (1.8%), An. peditaeniatus Leicester (0.3%) and An.
      nigerrimus Giles (0.1%). The four most abundant species were significantly
      associated with waterlogged fields and communal village drinking-water tanks.
      Habitat characteristics most correlated with occurrence of anophelines were the
      physical water condition and the absence/presence of fauna, particularly
      predators. Occurrence and abundance of Anopheles immatures were not significantly
      correlated with water temperature, DO, EC or pH. Malaria vectors of the Anopheles
      culicifacies complex occurred at relatively low densities, mainly in irrigated
      and waterlogged fields. In South Punjab, where rainfall is very low, it should be
      possible to reduce anopheline breeding through water management, as larvae
      develop mainly in water bodies that are directly or indirectly related to the
      extensive canal-irrigation system.

PMID- 11583441
TI  - Development rates of two Xenopsylla flea species in relation to air temperature
      and humidity.
AB  - The rate of development of immature fleas, Xenopsylla conformis Wagner and
      Xenopsylla ramesis Rothschild (Siphonaptera: Xenopsyllidae) was studied in the
      laboratory at 25 degrees C and 28 degrees C with 40, 55, 75 and 92% relative
      humidity (RH). These fleas are separately associated with the host jird Meriones
      crassus Sundevall in different microhabitats of the Ramon erosion cirque, Negev
      Highlands, Israel. This study of basic climatic factors in relation to flea
      bionomics provides the basis for ecological investigations to interpret reasons
      for paratopic local distributions of these two species of congeneric fleas on the
      same host. Both air temperature and RH were positively correlated with duration
      of egg and larval stages in both species. Change of humidity between egg and
      larval environments did not affect duration of larval development at any
      temperature. At each temperature and RH, the eggs and larvae of X. ramesis did
      not differ between males and females in the duration of their development,
      whereas female eggs and larvae of X. conformis usually developed significantly
      faster than those of males. For both species, male pupae developed slower than
      female pupae at the same air temperature and RH. Air temperature, but not RH,
      affected the duration of pupal development. At each humidity, duration of the
      pupal stage was significantly longer at 25 degrees C than at 28 degrees C: 15.3+/
      1.7 vs. 11.7+/-1.2 days in X. conformis; 14.1+/-2.0 vs. 11.5+/-1.7 days in X.
      ramesis, with a significantly shorter pupal period of the latter species at 25
      degrees C. These limited interspecific bionomic contrasts in relation to basic
      climatic factors appear insufficient to explain the differential habitat
      distributions of X. conformis and X. ramesis.

PMID- 11583443
TI  - Mapping distributions of chromosomal forms of Anopheles gambiae in West Africa
      using climate data.
AB  - The mosquito Anopheles gambiae Giles sensu stricto (Diptera: Culicidae), the
      principal vector of malaria in West Africa, comprises several chromosomal forms
      (e.g. Bissau, Forest, Mopti, Savanna) associated with climatic zones. Here we
      show how climate data can be used to map the geographical distribution of these
      chromosomal forms. The climate at 144 sites surveyed for mosquitoes in West
      Africa between 1971 and 92 was determined using computerized climate surfaces.
      Forest and Bissau forms occurred at relatively wet sites: median annual
      precipitation 1325 mm and 1438 mm, respectively, interquartile ranges (IQR) 1144
      1858 mm and 1052-1825 mm), whilst the Mopti form was found at dry sites (annual
      938 mm, IQR 713-1047 mm) and the Savanna form at sites intermediate between the
      wet and dry forms (annual 1067 mm, IQR 916-1279). Logistic regression analyses of
      the climate variables were carried out on a stratified random sample of half the
      sites. The resulting models correctly classified over 80% of the sites for
      presence or absence of each chromosomal form. When these models were tested
      against excluded sites they were also correct at over 80% of sites. The combined
      data produced models that were correct at over 86% of sites. Mean annual
      precipitation, evapotranspiration, minimum temperature and maximum temperature
      were the most important climate variables correlated with the distribution of
      these forms of An. gambiae. We used the logistic models to map the distribution
      of each chromosomal form within the reported range for An. gambiae s.s. in West
      Africa employing a geographical information system. Our maps indicate that each
      chromosomal form favours particular climate envelopes in well-defined ecoclimatic
      zones, although these forms are sympatric at the edges of their ranges. This
      study demonstrates that climate can be used to map the distribution of
      chromosomal forms of insects across large areas.

PMID- 11583442
TI  - Electroantennogram and behavioural responses of the malaria vector Anopheles
      gambiae to human-specific sweat components.
AB  - Afrotropical malaria vectors of the Anopheles gambiae complex (Diptera:
      Culicidae), particularly An. gambiae sensu stricto, are attracted mainly to human
      hosts. A major source of human volatile emissions is sweat, from which key human
      specific components are the carboxylic acids (E)- and (Z)-3-methyl-2-hexenoic
      acid and 7-octenoic acid. Electrophysiological studies on the antennae of An.
      gambiae s.s. showed selective sensitivity to these compounds, with a threshold at
      10(-6) g comparable to that of known olfactory stimulants 1-octen-3-ol, p-cresol,
      isovaleric acid, and lower than threshold sensitivity to L-lactic acid and the
      synthetic mosquito repellent N,N-diethyltoluamide (DEET). A combination of the
      acids released at concentrations > 10(-5) g in wind tunnel bioassays
      significantly reduced the response to CO2, the major attractant released by human
      hosts, for strains of An. gambiae s.s. originating from East and West Africa.
      Field trials with odour-baited entry traps (OBETs) in Burkina Faso showed that 7
      octenoic acid significantly increased (by 1.7-fold) the catch of females of An.
      gambiae sensu lato (comprising two sibling species: An. arabiensis Patton and An.
      gambiae s.s.) in OBETs baited with CO2, whereas combinations of the acids
      significantly reduced the catch in CO2-baited traps (by 2.1-fold) and in whole
      human odour-baited traps (by 1.5-fold). The pure (E) and (Z) geometric isomers of
      3-methyl-2-hexenoic acid gave comparable results to the (EIZ) isomer mixture.
      These results provide the first experimental evidence that human-specific
      compounds affect the behaviour of highly anthropophilic An. gambiae s.l.
      mosquitoes. The compounds appear to inhibit the upwind flight' response to known
      long-range attractants, and may serve either to mask' the attractants present or,
      more probably, to 'arrest' upwind flight when mosquitoes arrive at a host under
      natural conditions. In the final approach to hosts, vectors are known to reduce
      their flight speed and increase their turning rate, to avoid overshooting the
      source. In our experimental apparatus, these changes in flight behaviour would
      reduce the number of mosquitoes entering the ports of the collection devices.

PMID- 11583444
TI  - Testicular maturation in the sheep bot fly Oestrus ovis.
AB  - The process of testicular maturation in relation to intrapuparial development was
      studied in the sheep nasal bot fly, Oestrus ovis L. (Diptera: Oestridae). After
      formation of the puparium during larval-pupal apolysis and the cryptocephalic
      pupal stage (approximately 24-72 h), spermatogonia had undergone mitotic
      divisions and sperm cysts had been formed. Five days after pupariation,
      spermatogonia transformed into primary spermatocytes during the phanerocephalic
      pupal stage, and secondary spermatocytes first appeared during the pupal-adult
      apolysis. Secondary spermatocytes began undergoing the second meiotic division by
      day 8 (transparent-eye pharate adult stage). By days 9 and 10, round spermatids
      were present and began to elongate by day 11. By day 12, the first bundles of
      tailed spermatozoa had appeared. By day 15 (the yellow-orange eye pharate adult
      stage), round, elongated, tailed and bundled spermatids were predominant and by
      day 17 differentiating spermatids occupied nearly 35% of the testicular cavity,
      and 60% was occupied by free sperm. By day 21 (the red-brown eye pharate adult
      stage), spermatozoa colonized the seminal vesicle. At emergence (approximately
      day 22), a complement of free sperm occupied the testis and the seminal vesicle,
      but groups of developing cells frequently remained in certain zones.
      Spermatogenesis was carried out after pupariation and spermiogenesis occurred
      during the pharate adult stage. After emergence, males possessed fully formed
      spermatozoa ready for ejaculation.

PMID- 11583445
TI  - Bloodmeal digestion and Leishmania major infections in Phlebotomus duboscqi:
      effect of carbohydrates inhibiting midgut lectin activity.
AB  - The carbohydrates galactosamine and heparin, previously shown to inhibit
      phlebotomine lectin activity in vitro, were fed to the sandfly Phlebotomus
      duboscqi Neveu-Lemaire (Diptera: Psychodidae) with blood, and the effects on
      mortality, fecundity, protease activity and susceptibility to Leishmania major
      Yakimoff & Schokhor (Kinetoplastida: Trypanosomatidae) were studied. Previous
      study revealed that galactosamine considerably enhanced the establishment of L.
      major infection in P. duboscqi and significantly increased parasite loads in late
      infections. This work demonstrates a similar but less pronounced effect of
      heparin. Heparin increased infection rates and parasite loads 3 and 9 days post
      feeding but did not affect the location of Leishmania promastigotes and their
      anterior migration. Galactosamine supplement caused pronounced changes in
      bloodmeal digestion. It abolished the activity of alkaline proteases and trypsin,
      caused premature defecation of bloodmeal, increased mortality of female sandflies
      in days 1-4 post-feeding and decreased their fecundity. Heparin had a less
      pronounced effect on sandfly physiology. It lowered trypsin activity 12 and 72 h
      post-bloodmeal but did not alter defecation, mortality and oviposition. The data
      suggest that the enhancing effect of these carbohydrates on Leishmania infections
      in sandfly midgut could be explained by their interference with midgut proteases.
      The study supports the hypothesis that proteolytic activities of midgut proteases
      strongly influence the vector competence of sandflies.

PMID- 11583447
TI  - Unexpected anthropophagic behaviour in Anopheles quadriannulatus.
AB  - The strongly anthropophilic behaviour of Anopheles gambiae Giles sensu stricto
      (Diptera: Culicidae), the most important malaria vector in Africa, has been
      demonstrated by field and laboratory studies. Other members of the An. gambiae
      complex express varied degrees of anthropophily. Anopheles quadriannulatus
      (Theobald) species A and B are more zoophilic members of the complex and hence
      are considered to be of no medical importance. Olfactometer experiments with An.
      quadriannulatus species A have demonstrated attraction to both human and cow
      odour. To extend these olfactometer observations a choice experiment was
      conducted in an outdoor cage with a human and a calf as baits, using laboratory
      reared mosquitoes. Anopheles gambiae s.s. (from Liberia) and two strains of An.
      quadriannulatus species A (SKUQUA from South Africa, SANGQUA from Zimbabwe),
      marked with different coloured fluorescent powders for identification purposes,
      were released simultaneously and given an equal opportunity to feed on either
      host. The experiment was repeated six times. Bloodmeals were identified using the
      precipitin technique. Anopheles gambiae s.s. showed highly anthropophagic
      behaviour, taking 88% of bloodmeals from the human host. In contrast, both
      strains of An. quadriannulatus fed with equal frequency on the human or the calf;
      the response to either host was not significantly different. These results
      confirm the olfactometer findings and demonstrate anthropophagic behaviour not
      previously recorded in this species. This finding has implications for
      prospective manipulation of host preference for genetic control purposes.

PMID- 11583446
TI  - Repellent effects on Anopheles arabiensis biting humans in Kruger Park, South
      Africa.
AB  - Distribution of biting sites on the human body by the malaria vector Anopheles
      arabiensis Patton (Diptera: Culicidae) was investigated near a source of
      mosquitoes in the Kruger National Park, South Africa. Eight adult male volunteers
      (2 teams x 2 pairs of subjects) conducted human bait collections while seated on
      camp chairs in the open-air, wearing only short trousers (no shirt, socks or
      shoes). Mosquito collections during 18.30-22.30 hours on five consecutive nights
      in April 1998 yielded a total of 679 An. arabiensis females biting subjects with
      or without their ankles and feet treated with deet insect repellent (15% diethyl
      3-methylbenzamide, Tabard lotion). On subjects whose feet and ankles were smeared
      with repellent, 160 An. arabiensis females were captured biting in 60 manhours:
      88.1% on the legs, 1.4% on the arms and 1.2% on other parts of the body, but none
      on the repellent-treated feet or ankles. On subjects without repellent treatment,
      519 An. arabiensis were caught biting in 60 man-hours: 81.1% on feet and ankles,
      16.4% on legs, 1.4% on arms and 1.2% on the rest of the body. For individual
      subjects, the reduction of An. arabiensis bites ranged from 36.4 to 78.2% (mean
      protection 69.2%). Results of this study confirm previous findings that, in this
      part of South Africa - inhabited only by wildlife - when people sit outside
      during the evening An. arabiensis prefers to bite their lower limbs: 97.5% below
      the knees. Overall, the number of bites by the malaria vector An. arabiensis was
      reduced more than three-fold (from 26 to 8/person/evening), simply by treating
      ankles and feet with a consumer brand of deet repellent. Whether or not this
      provides a satisfactory degree of protection against malaria risk would depend on
      the malaria sporozoite rate in the malaria vector population.

PMID- 11583448
TI  - Palatability and toxicity of fipronil as a systemic insecticide in a bromadiolone
      rodenticide bait for rat and flea control.
AB  - Vector control in plague-infested areas requires a simultaneous killing of
      rodents and their fleas. We investigated the efficacy of a combination of a
      systemic insecticide, fipronil, in a rodenticide bait formulation under
      laboratory conditions. Four different concentrations of fipronil (0.05%, 0.005%,
      0.0005% with acetone as a solvent, and 0.05% with propylene glycol as a solvent)
      and two controls (solvents only) were combined with the rodenticide bait (crushed
      organically grown wheat with 0.005% bromadiolone). Each concentration was offered
      together with an untreated non-poisonous challenge bait to 10 singly caged Rattus
      rattus L., each with 100 rat fleas Xenopsylla cheopis Rothschild (Siphonaptera:
      Pulicidae) in the nest. Treated bait consumption was relatively low and an
      unsatisfactory rat mortality of around 50% only was obtained in all tests. The
      palatability of the bait, however, was not affected by the fipronil
      concentration. Even at the lowest fipronil concentration, average flea mortality
      was still above 95%, and doses of more than I mg fipronil per kg rat body weight
      gave a nearly complete kill of fleas. Fipronil can be highly effective as a
      systemic insecticide to for flea control, provided that a more attractive bait
      base for roof rats is used.

PMID- 11583449
TI  - Tick-borne encephalitis virus in northern Italy: molecular analysis,
      relationships with density and seasonal dynamics of Ixodes ricinus.
AB  - Ixodes ricinus ticks were collected from dragging vegetation and from shot roe
      deer in the province of Trento and Belluno in northern Italy. Ticks were pooled
      for analyses and from 1060 pools of ticks collected in the province of Belluno
      and 12390 tick samples collected in Trentino, four proved positive by
      immunofluorescence microscopy using a tick-borne encephalitis (TBE)-specific
      antiserum. The identity of the virus isolates was determined by RT-PCR cycle
      sequencing and they were all found to be closely similar (> 98% nucleotide
      identity) to typical western European TBE complex viruses as found in Austria.
      The isolates from Trentino differed from the Neudorfl strain of western European
      TBE virus at eight nucleotide positions but as these nucleotide substitutions
      were all synonymous, there were no amino acid changes. These results imply that
      the virus isolates in Trentino have changed slightly from the typical European
      strains isolated in nearby Austria. The abundance of questing ticks and ticks
      feeding on roe deer was greater in TBE positive hunting districts than in hunting
      districts where TBE complex viruses were only probable or believed to be absent.
      In TBE positive and probable districts synchrony in the seasonal dynamics of
      larvae and nymphs of L. ricinus was observed. This study provides evidence to
      suggest that roe deer may have an important role to play in the maintenance of
      tick density and in the persistence of TBE virus.

PMID- 11583450
TI  - Human and other faeces as breeding media of the trachoma vector Musca sorbens.
AB  - The fly Musca sorbens Wiedemann (Diptera: Muscidae) apparently transmits
      Chlamydia trachomatis, causing human trachoma. The literature indicates that M.
      sorbens breeds predominantly in isolated human faeces on the soil surface, but
      not in covered pit latrines. We sought to identify breeding media of M. sorbens
      in a rural Gambian village endemic for trachoma. Test breeding media were
      presented for oviposition on soil-filled buckets and monitored for adult
      emergence. Musca sorbens emerged from human (6/9 trials), calf (3/9), cow (3/9),
      dog (2/9) and goat (1/9) faeces, but not from horse faeces, composting kitchen
      scraps or a soil control (0/9 of each). After adjusting for mass of medium, the
      greatest number of flies emerged from human faeces (1426 flies/kg). Median time
      for emergence was 9 (inter quartile range = 8-9.75) days post-oviposition. Of all
      flies emerging from faeces 81% were M. sorbens. Male and female flies emerging
      from human faeces were significantly larger than those from other media,
      suggesting that they would be more fecund and live longer than smaller flies from
      other sources. Female flies caught from children's eyes were of a similar size to
      those from human faeces, but significantly larger than those from other media. We
      consider that human faeces are the best larval medium for M. sorbens, although
      some breeding also occurs in animal faeces. Removal of human faeces from the
      environment, through the provision of basic sanitation, is likely to greatly
      reduce fly density, eye contact and hence trachoma transmission, but if faeces of
      other animals are present M. sorbens will persist.

PMID- 11583451
TI  - Evaluation of biological and chemical insecticide mixture against Aedes aegypti
      larvae and adults by thermal fogging in Singapore.
AB  - To improve the operational efficiency of dengue vector control in Singapore,
      larvicide and adulticide were applied together by thermal fog generator (Agrofog
      AF40). The mixture consisted of Bacillus thuringiensis var. israelensis (Vectobac
      12 AS) as biological larvicide at 1.5 L/ha and pirimiphos-methyl (Actellic 50 EC)
      as adulticide at 100 g ai/ha, diluted 10-fold with water. Aerosol of this mixture
      was evaluated against the mosquito Aedes aegypti (L.) (Diptera: Culicidae) in
      bioassays using cages of 10 adult females exposed at heights of 0.3-2.4 m and
      distances of 3-12 m from the hand-held generator. Cups containing 200 mL water
      were treated at ground level by exposure to the aerosol application at the same
      distances from the generator. Subsequent larval bioassays on days 1, 7, 14, 21
      and 28 post-spray involved exposing 20 larvae/cup for 48 h. Droplets had VMD 57
      microm and female mosquitoes were killed by 2 s exposure to the aerosol at 3 m.
      We obtained 92-100% mortality of the adult mosquitoes and 100% control of larvae
      at 3 m distance, but only 10-13% mortality at 12 m from the fogger. In treated
      cups, larvae showed high mortality (92%) when exposed for 48 h even 1 month post
      treatment. Results demonstrate the practical advantage of using this mixture of
      Vectobac 12AS and Actellic 50 EC for simultaneous control of Aedes adults and
      larvae, with prolonged larvicidal efficacy in treated containers.

PMID- 11583452
TI  - Pre-adult mortality in the blowfly Lucilia sericata.
AB  - Populations of the blowfly, Lucilia sericata (Meigen) (Diptera: Calliphoridae),
      have a considerable potential for rapid increase; the lifetime reproductive
      output of each adult female has been estimated to be between 130 and 172 eggs.
      Nevertheless, in the field, absolute population densities of this species are
      relatively low. To account for this difference, the levels of mortality affecting
      the eggs, feeding and wandering larvae and pupae of L. sericata were assessed in
      the field and laboratory. Percentage egg hatch was dependent on relative humidity
      with no egg eclosion at humidities below 50%; there was no significant effect of
      temperature on egg hatch. On infested sheep, the mean mortality of feeding larvae
      was 53%, but this ranged widely from 0% to 96%. There was no effect of
      atmospheric temperature or humidity on the mortality of feeding larvae in vivo.
      In the laboratory, only 10% of wandering larvae pupariated at 10 degrees C. At
      above 20 degrees C pupariation was consistently almost 100%. Percentage emergence
      increased from 0% at 10 degrees C to about 80% between 20 and 30 degrees C. The
      upper lethal temperature for pupae was approached at 35 degrees C. Analysis of
      the predation of pupae in the field revealed a weak, but significant curvilinear
      relationship between temperature and proportionate mortality and a median
      mortality of 0.49% per 24 h exposure (interquartile range = 5.2%). There was no
      evidence of density dependence in pupal predation. Overall, it is estimated that
      pre-adult mortality accounts for losses of approximately 97% of each generation,
      but this figure is subject to considerable variation depending on factors such as
      climate, time of year and host susceptibility.

PMID- 11583453
TI  - Ixodes rubicundus nymphs are short-day diapause-induced ticks with thermolabile
      sensitivity and desiccation resistance.
AB  - The Karoo Paralysis tick, Ixodes rubicundus Neumann (Acari: Ixodidae), is a semi
      voltine ixodid that survives stressful environmental conditions using
      morphogenetic diapause (eggs and engorged nymphs) and desiccation resistance.
      Both photoperiod and temperature influence diapause induction in the engorged
      nymph. Ixodes rubicundus nymphs are typical long-day photoperiodic organisms. The
      critical photoperiod is approximately 13.5 h light, 10.5 h dark, and they display
      a thermolabile response. The period between detachment and apolysis in engorged
      nymphs is modified by photoperiod; however, apolysis to ecdysis is not affected
      by photoperiod. Thus, initiation of development, but not the actual process is
      controlled by photoperiod. Most engorged nymphs delayed metamorphosis when
      exposed to short-day regimen (LD 12 : 12 h) after feeding. Nymphs exposed to pre-
      and post-feeding long-day regimen (LD 14 : 10 h) developed. Times for 50% of
      nymphs to apolyse when exposed to photoperiods of LD 14 : 10 h, 13.5 : 10.5 h, 13
      : 11 h and 12 : 12 h were 28, 36, 40 and 58 days, respectively. Times for 50% of
      engorged nymphs to ecdyse ranged from 38 to 40 days after apolysis. Nymphs were
      sensitive to photoperiodic exposures before, during and after feeding. Nymphs
      exposed to long day (LD 14 :10 h) before and during feeding, moulted at 20
      degrees C; however, most exposed to 10 degrees C followed by 20 degrees C (post
      feeding) went into diapause. Both short- (10 : 14 h) and long- (14 : 10 h) day
      exposed engorged nymphs survived 45 days at 0% r.h. (n = 73), but diapause
      destined ticks kept at 13 degrees C lost the least mass (29.5+/-9.5%, SD), while
      nondiapause ticks at 23 degrees C lost the most (48.7+/-8.2%, SD). Termination of
      diapause and transition to development probably coincides with a definite
      increase of water vapour uptake by engorged nymphs. Comparatively, I. rubicundus
      engorged nymphs are more desiccation tolerant than a North-American counterpart,
      Amblyomma cajennense (Fabricius) (Acari: Ixodidae), which is also semi-arid- to
      xeric-adapted. Diapause conveys important survival attributes that enable
      engorged I. rubicundus nymphs to inhabit a semi-arid environment with great
      temperature extremes, and to synchronize their activity periods with seasons and
      host utilization patterns.

PMID- 11583454
TI  - Accumulation and persistence of flea larvicidal activity in the immediate
      environment of cats treated with imidacloprid.
AB  - To investigate the persistence of flea larvicidal activity in the immediate
      environment of cats treated with imidacloprid, eggs of the cat flea
      Ctenocephalides felis felis Bouche (Siphonaptera: Pulicidae), from untreated
      donor cats, were incubated on samples of fleece blanket taken from the floor of
      cages used by treated or untreated cats for a total of 10 or 20 6-h periods over
      2-4 weeks, respectively. Sufficient imidacloprid accumulated during these periods
      to reduce the emergence of adult fleas by 94.7-97.6% when the blankets were
      tested after 18 weeks' storage at room temperature. A typical laundry procedure
      (washing with detergent at 50 degrees C and low temperature tumble drying)
      removed this biological activity. Unwashed control blankets did not support the
      flea life-cycle as effectively as washed blankets or a sand substrate.

PMID- 11583455
TI  - Control of the buffalo fly Haematobia irritans exigua in India, using the
      pyrethroids deltamethrin and fenvalerate.
AB  - The effectiveness of two pyrethroids, fenvalerate and deltamethrin, against the
      fly Haematobia irritans exigua de Meijere (Diptera: Muscidae) on buffalo was
      considered in a field trial. Fenvalerate provided 100% control for 1, 2 and 4
      weeks at concentrations of 0.03, 0.04 and 0.05%, respectively. Concentrations of
      0.01 and 0.02% were less effective. One hundred percent control of this fly was
      obtained with deltamethrin for 2, 3 and 6 weeks at concentrations of 0.003, 0.004
      and 0.005%, respectively. Deltamethrin concentrations of 0.001% and 0.002%
      achieved fly control for only 1-2 weeks, respectively.

PMID- 11583456
TI  - How does drug and alcohol misuse develop among people with psychotic illness? A
      literature review.
AB  - BACKGROUND: There is little evidence contributing to the understanding of why
      people with schizophrenia and other psychotic illnesses use drugs and alcohol.
      METHOD: A comprehensive literature search for evidence relevant to each of the
      following questions was undertaken, each of which is relevant to understanding
      why individuals with schizophrenia and other functional psychotic illnesses use
      drugs and alcohol: (1) Is substance misuse more prevalent among those with
      psychotic illness than the general Population? (2) Which problem generally
      develops first in dual diagnosis? (3) Can substance misuse cause schizophrenia
      and other functional psychotic illnesses? (4) Does dual diagnosis have a
      neurobiological Basis? (5) Is personality disorder a mediating factor in the
      relationship between psychotic illnesses and substance misuse? (6) Do individuals
      with psychotic illness use substances as self-medication? (7) Have changes in the
      care and social circumstances of people with psychotic illness, particularly
      deinstitutionalisation, led to a rise in substance misuse in this Population? (8)
      Do the social situations and social difficulties of people with psychotic illness
      lead to substance misuse? and (9) Do individuals with psychotic illness tend to
      begin using drugs and alcohol within mental health service settings or in the
      company of other users of such services? RESULTS: There is some evidence to
      support the idea that people with schizophrenia and other psychotic disorders use
      substances to reduce general dysphoria, and possibly negative symptoms. Social
      environment and experiences are also likely to be factors in the development of
      substance misuse in this group, but there is a dearth of empirical evidence.
      CONCLUSIONS: There is a need for further research, especially concerning the
      social contexts of substance and alcohol misuse and the ways in which patterns of
      misuse develop among people with schizophrenia and other psychotic illnesses.

PMID- 11583457
TI  - Road rage: a psychiatric phenomenon?
AB  - BACKGROUND: Road rage is a concept recently popularised by the press. An
      association with psychiatric illness is implied from reports of such drivers
      being "mad". Previous literature has demonstrated a link between road traffic
      accidents and mental illness. This study examines the relationship between road
      rage and psychiatric morbidity. It aims to estimate the prevalence of road rage
      by self-report and elucidate demographic and psychiatric factors associated with
      road rage. METHOD: This is a cross-sectional study of attendees at general
      practice clinics that examines self-reported road rage and psychiatric morbidity.
      Assessment was based on the total score on the Clinical Interview Schedule
      (revised version; CIS-R), Aggression Questionnaire, Screening Test for Comorbid
      Personality Disorders, Alcohol Use Disorders Identification Test and Life Events
      Schedule. RESULTS: Fifty-three percent of 131 subjects reported a recent incident
      of road rage. Perpetrator and victim groups differed from controls. Perpetrators
      had increased aggression scores and psychiatric morbidity. There was a strong
      association with male sex and illicit drug use, and a strong negative association
      with driving experience. A weaker association was found with youth. Victims
      showed increased psychiatric morbidity and were more likely than perpetrators to
      seek help for emotional problems. Life events stress, social class, alcohol use
      and personality disorder had no significant effect. CONCLUSION: There is an
      association between road rage and psychiatric morbidity.

PMID- 11583458
TI  - Do the Chinese somatize depression? A cross-cultural study.
AB  - BACKGROUND: A large literature argues for the Chinese--whether in mainland China
      or elsewhere--being highly likely to express depression somatically, leading to
      predictable detection and diagnostic difficulties. If true, detection might be
      assisted if a set of somatic proxies of depression were identified, and this was
      the principal initial objective in mounting this study. METHODS: We studied two
      sets of depressed outpatients, one of Malaysian Chinese and the other of
      Australian Caucasians, matched by age and sex. We identified the prime symptom
      nominated by them when they first sought assistance, and required them to
      complete an inventory of both somatic and cognitive symptoms, and rank the three
      items they judged as most capturing their distress. RESULTS: The Chinese were
      distinctly more likely to nominate a somatic symptom as their presenting
      complaint (60% vs 13%), while the Australian subjects were more likely to
      nominate depressed mood, cognitive and anxiety items. Responses to the inventory
      established that the Chinese did score somewhat higher on a somatic set of items,
      but differed far more distinctly in being less likely to affirm cognitive items
      of depression, resulting in significantly lower total inventory scores. Variation
      across the contrast samples in acknowledging the presence of symptoms did not
      relate simply to the prevalences of those symptoms. CONCLUSIONS: Our failure to
      identify a culture-specific somatic factor as a proxy of depression, together
      with establishing a high rate of somatic and related items (e. g. insomnia) in
      both samples, may largely reflect the phenomenon of 'corporization', whereby
      depressed patients irrespective of culture are more likely to experience and
      report in response to a 'somatosensory amplification' influence.

PMID- 11583459
TI  - Child and adolescent mental health service use in Finland.
AB  - BACKGROUND: The study examines the associations of parent, teacher and self
      report evaluations of child psychopathology, help-seeking variables and family
      factors with the use of child mental health services. METHOD: The study comprised
      an 8-year follow-up of the Epidemiological Child Psychiatry Study in Finland.
      Children were evaluated at age 8 with Rutter parent and teacher scales and with
      the Child Depression Inventory, and at age 16, with the Child Behavior Checklist
      and the Youth Self Report. Information was obtained from about 70% of the follow
      up sample (n=857). RESULTS: About 7% of the sample had been in contact with child
      mental health services during the follow-up. The most potent predictors at age 8
      of later referral were total problem behaviours and antisocial problems in
      parental evaluation, teacher's evaluation of the child's need for referral and
      living in other than a biological two-parent family. At age 16, externalizing and
      internalizing problems, total competence and family composition were
      independently associated with service use. CONCLUSIONS: Both child
      psychopathology and family disruption were associated with service use. Only a
      minority of children at risk of psychiatric disorders had used child mental
      health services.

PMID- 11583460
TI  - Perception of stigma among family members of individuals with schizophrenia and
      major affective disorders in rural Ethiopia.
AB  - BACKGROUND: Many studies from the Western world have reported on stigmatisation
      of people with mental illnesses and its negative consequences, but few studies
      have addressed the issue in traditional rural societies. The present study aimed
      to estimate the extent and socio-demographic distribution of stigma as perceived
      by relatives of mentally ill individuals in rural Ethiopia. METHOD: A total of
      178 relatives of individuals who were diagnosed as suffering from schizophrenia
      or major affective disorders in a community-based survey were interviewed using
      the Family Interview Schedule. RESULTS: About 75% of the respondents perceived
      that they were stigmatised or had experienced some sort of stigma due to the
      presence of mental illness in the family, 42% were worried about being treated
      differently and 37% wanted to conceal the fact that a relative was ill. Those
      from the older age group (45+) and urban residents were more likely to perceive
      stigma as a major problem, but otherwise differences were few between socio
      demographic groups. The illness was attributed to supernatural forces by 27% and
      praying was suggested as a preferred method to deal with the problem by 65%.
      CONCLUSION: Stigma was found to be a common problem, with few differences between
      socio-demographic groups or between types of mental disorder. Beliefs about
      causes differ from those held by professionals. Popular beliefs and attitudes
      must be taken into account when planning for intervention.

PMID- 11583461
TI  - Prediction of readmission to acute psychiatric units.
AB  - BACKGROUND: Many factors are known to influence readmission to psychiatric wards,
      and readmission rates have been suggested as proxy outcome indicators of quality.
      METHOD: Korner returns were used to ascertain readmission rates for all
      psychiatric admissions to acute wards in North Staffordshire, 1987-1993.
      Predictor variables were derived from Korner returns or obtained from the 1991
      Census data. Survival analysis techniques were used to examine which variables
      predicted readmission. RESULTS: A predictive model was derived using Cox
      regression, which followed the observed data at greater than chance probability
      (chi2=48.5, df=4, P < 0.001). A psychotic diagnosis was the most influential
      predictor of readmission. CONCLUSION: Length of stay is not predictive in the Cox
      regression model, which suggests patients are not being prematurely discharged.
      The derived models may have value in service planning, audit and resource
      allocation.

PMID- 11583462
TI  - Do mental health problems increase sickness absence due to other diseases?
AB  - BACKGROUND: The incidence of mental health problems is rising. Large sex
      differences are found for mental health problems, which also is reflected in sick
      leave. The aim of this study was to analyse the association of mental health
      problems with sickness absence in general. METHODS: Employed women (n = 1407) in
      four occupational groups, namely metal workers, enrolled nurses, medical
      secretaries and nurses, were included. Sick-leave data were collected through
      social insurance and employers' registers. Five indicators reflecting different
      aspects of mental health problems were analysed in relation to sickness absence.
      RESULTS: Women with mental health problems, irrespective of indicator used, had
      higher levels of sickness absence than women without mental health problems. The
      association was found for frequency, incidence, length and duration of sickness
      absence, and it was found also with respect to less severe forms of mental health
      problems. For example, women with worries had a frequency of 3.5 sick-leave
      spells per year, while women without worries had 2.5 spells. Furthermore, women
      with self-reported mental illness (SF-36) had a 1.93 times increase in sick-leave
      length over 1 year. CONCLUSIONS: We conclude that mental health problems need to
      be recognised in relation to sickness absence, rehabilitation and prevention in
      all diagnoses.

PMID- 11583463
TI  - Medialization framework surgery for voice improvement after endoscopic
      cordectomy.
AB  - Seven dysphonic patients who had previously undergone total or extended
      cordectomy underwent laryngeal framework medialization. A minimum 6-month period
      between cordectomy and framework surgery was enforced to allow the vocal cord to
      scar and form a fibrous "neocord", to evaluate the voice recovery achieved by
      speech therapy alone and avoid the risk of operating on a patient with
      undiagnosed early recurrence. The operation is performed with fiberscopic control
      under general anesthesia. These operating conditions are required because
      undermining the fibrous tissue at the inner side of the thyroid ala is a lengthy
      and laborious procedure. This step is necessary to ensure easy placement of the
      implant. Caution must be taken to avoid tearing the fibrous tissue, with
      consequent risk of prosthesis extrusion. The cartilage window is left intact.
      Whereas cartilage implants remain indicated for minor gaps, we advocate
      Friedrich's implant for wider gaps. The vocal outcome revealed an increased
      median maximum phonation time from 5 s (range 2-12 s) to 7.5 s (range 3-23 s); a
      reduced phonation quotient from 516.5 ml/s (range 235-1000 ml/s) to 222 ml/s
      (range 146-595 ml/s); a slightly increased modal intensity from 61.5 dB (range 57
      75 dB) to 67 dB (range 46-68 dB); an improved intensity range from 24.5 dB (range
      16-36 dB) to 30 dB (range 16-62 dB); a steady fundamental frequency from 150 Hz
      (range 132-290) to 152 Hz (range 125-200); and an increased median spectral
      analysis class from 2 (range 1-3) to 3 (range 2-4). Subjectively, the patients
      noted that, throughout the day, phonation required less effort and induced less
      vocal fatigue.

PMID- 11583464
TI  - Cartilage invasion of laryngeal cancer detected by magnetic resonance imaging.
AB  - Cartilage invasion of laryngeal cancer has a significant impact on the choice of
      treatment modality and on the outcome for the patients. Cartilage invasion was
      evaluated radiologically and histopathologically in 18 patients who underwent
      total laryngectomy. The histopathological examination showed intracartilaginous
      tumor spread in nine specimens, whereas in the other nine no cartilage invasion
      was found. Magnetic resonance imaging (MRI) detected the cartilage invasion in
      six patients and excluded it in six. There were three false negative and three
      false positive findings from the MRI examination. The relatively common false
      findings of MRI should be kept in mind in the choice of treatment.

PMID- 11583465
TI  - Quality of life of patients with laryngeal carcinoma: a post-treatment study.
AB  - This study was designed to determine the quality of life of patients successfully
      treated for laryngeal cancer. A questionnaire was mailed to 233 patients. A total
      of 124 responses were suitable for analysis. The questionnaire consisted of three
      components: sociodemographic data, European Organisation for Research and
      Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ - C 30,
      version 2.0), and EORTC QLQ, Head and Neck Module (H & N 35). The assessment
      included five treatment groups: chordectomy, partial laryngectomy, irradiation as
      primary therapy, laryngectomy, laryngectomy and radiotherapy. The evaluation for
      the functional scales of the EORTC QLQ - C 30 resulted in a higher quality of
      life of patients with maintained larynx in comparison to laryngectomised
      patients. In the symptom scales, patients after laryngectomy and/or radiotherapy
      suffered more from fatigue, pains and appetite loss. Laryngectomees stated more
      financial difficulties. The evaluation of the ENT-specific EORTC module showed
      that patients after laryngectomy had more symptoms. Typical symptoms after
      radiotherapy were a dry mouth, sticky saliva and coughing. Noticeably, no
      differences existed among the several groups with regard to voice production. The
      EORTC QLQ- H & N 35 does not appear to be sensitive enough to assess this
      parameter.

PMID- 11583466
TI  - Advances and refinements in surgical voice rehabilitation after laryngectomy.
AB  - After Blom and Singer reported the construction of the so-called "duck bill"
      prosthesis in 1980, there have been quite a few newer voice prostheses
      constructed by other workers and new methods developed to predict the results,
      such as the insufflation and lidocaine test. Implanting the voice prosthesis with
      the Blom-Singer method has presented some problems and complications related to
      the puncture technique, therefore the following simplified esophagotracheal
      puncture technique is presented. The pharynx is opened with the laryngoscope
      which is then led up to the entrance of the esophagus. Through the laryngoscope,
      the distal end of the endo-extralaryngeal needle carrier, developed by the author
      and modified for mass production by R. Wolf Ltd., Germany, is led into the
      esophagus. The instrument is pushed forward as long as its distal bent, blunt end
      is palpable in the upper third of the tracheostoma. The needle with the thread
      (2/0 prolene) is pushed through from the inside, out in the upper third of the
      tracheostoma. A double wire forming a loop is led through the pointed metal cone
      (containing a built-in needle) and the catheter and tied behind a counterfixing
      pierced ball. The 2/0 prolene leading thread is then knotted with the wire. By
      pulling the thread and the wire, the pointed end of the metal cone with the
      needle built-in, perforates the soft parts and pulls the catheter with it (the
      same procedure will be used for primary puncture as well). After this procedure
      the voice prosthesis can easily be placed in the fistula in a conventional
      manner. Using this technique, 59 patients could be implanted without puncture
      related complications or problems. Problems, not related to the puncture
      technique, such as Candida albicans infection etc., were solved using the well
      known treatment modalities. To stop leakage around the prosthesis, injection of
      Bioplastique into the soft tissue surrounding the fistula was used with success.

PMID- 11583467
TI  - Post-intubation vocal cord paralysis: the viral hypothesis. A case report.
AB  - After digestive surgery, a 20-year-old man presented dysphonia and fever.
      Indirect laryngoscopy revealed a left vocal cord paralysis with no structural
      lesion. IgM and IgG were positive for cytomegalovirus and negative for human
      immunodeficiency virus, herpes simplex virus, varicella zoster virus and Epstein
      Barr virus. The patient recovered spontaneously with a normal voice, and the
      mobility of vocal cord recovered within 3 months. The aetiology of post
      intubation vocal cord paralysis (VCP) remains controversial. Vocal cord paralysis
      with cytomegalovirus has been reported in two cases associated with acquired
      immunodeficiency syndrome. Vocal cord paralysis secondary to viral disease has
      also been described in other circumstances. panied by polyneuritis, especially in
      immunocompromised patients. We report the case of a patient with transitory
      unilateral post-intubation vocal cord paralysis which could have been related to
      a virus infection.

PMID- 11583468
TI  - A topical steroid without an antibiotic cures external otitis efficiently: a
      study in an animal model.
AB  - In an animal external otitis model, inflammatory reactions were evoked by
      mechanical stimulation of the rat ear canal skin. The rats were in four groups:
      group A treated with a group III steroid, betamethasone dipropionate; group B
      treated with hydrocortisone combined with oxytetracycline; group C treated with
      hydrocortisone with oxytetracycline and polymyxin B added; Group D, the controls,
      treated with saline. All rats were observed otomicroscopically daily during the
      first 7 days after treatment and then on days 10 and 20. A standardized scoring
      system was used to evaluate colour, swelling and effusion of the ear canal.
      Histological specimens were collected on days 3, 7, 10 and 20. The most rapid
      improvement in the ear canal status occurred in the animals treated with
      betamethasone dipropionate. The inflammatory reaction of the ear canal skin
      caused by mechanical stimulation was characterized by oedema of the stroma but
      few inflammatory cells were present. The surface of the epithelium towards the
      connective tissue layer was smooth in the group III-treated animals (group A)
      whereas other groups had irregularities of the basal membrane. From this study it
      is inferred that the group III steroid betamethasone dipropionate alone heals
      experimentally induced external otitis more rapidly than hydrocortisone with
      oxytetracycline, with or without polymyxin B. These findings should be considered
      in future clinical trials of external otitis.

PMID- 11583469
TI  - Pharyngeal and hypopharyngeal reconstruction after multilating surgery for
      malignant hypopharyngeal cancers.
AB  - The authors summarise their reconstructive surgical experience after the radical
      excision of hypopharyngeal tumours. In selective cases the preservation of the
      larynx is a reliable surgical option and supraglottic surgery is sufficient to
      remove the tumour. Myocutaneous paddle flaps were used in every case after the
      surgical resection for the reconstruction of the pharyngo-oesophageal entrance.
      After total circular pharyngo-laryngectomy, the continuity of the upper digestive
      tract was reconstructed by tubed myocutanous flaps.

PMID- 11583470
TI  - Apoptosis in the hydropic cochlea of guinea pigs following immune reaction of the
      endolymphatic sac: immunohistochemical analysis.
AB  - Apoptotic change in the cochlea was studied by immunohistochemistry after the
      injection of keyhole limpet haemocyanin (KLH) into the right endolymphatic sac of
      guinea pigs. Apoptosis was examined with the specific antibody to single-stranded
      DNA (ssDNA). Endolymphatic hydrops became evident in the cochlea 1 day after the
      injection of KLH (n = 6). Increased ssDNA expression could be detected in the
      spiral ligament and the stria vascularis. The temporal bones in the control group
      did not show any ssDNA immunoreactivity (n = 6). Apoptosis is the process of the
      cell death. Our findings imply that apoptotic changes are involved in
      endolymphatic hydrops. These phenomena could lead to cochlear dysfunction as seen
      in endolymphatic hydrops.

PMID- 11583471
TI  - Relative contribution of CYP3A to amitriptyline clearance in humans: in vitro and
      in vivo studies.
AB  - The relative contribution of cytochrome P450 3A (CYP3A) to the oral clearance of
      amitriptyline in humans has been assessed using a combination of in vitro
      approaches together with a clinical pharmacokinetic interaction study using the
      CYP3A-selective inhibitor ketoconazole. Lymphoblast-expressed CYPs were used to
      study amitriptyline N-demethylation and E-10 hydroxylation in vitro. The relative
      activity factor (RAF) approach was used to predict the relative contribution of
      each CYP isoform to the net hepatic intrinsic clearance (sum of N-demethylation
      and E-10 hydroxylation). Assuming no extrahepatic metabolism, the model-predicted
      contribution of CYP3A to net intrinsic clearance should equal the fractional
      decrement in apparent oral clearance of amitriptyline upon complete inhibition of
      the enzyme. This hypothesis was tested in a clinical study of amitriptyline (50
      mg, p.o.) with ketoconazole (three 200 mg doses spaced 12 hours apart) in 8
      healthy volunteers. The RAF approach predicted CYP2C19 to be the dominant
      contributor (34%), with a mean 21% contribution of CYP3A (range: 8%-42% in a
      panel of 12 human livers). The mean apparent oral clearance of amitriptyline in 8
      human volunteers was decreased from 2791 ml/min in the control condition to 2069
      ml/min with ketoconazole. The average 21% decrement (range: 2%-40%) was identical
      to the mean value predicted in vitro using the RAF approach. The central nervous
      system (CNS) sedative effects of amitriptyline were slightly greater when
      ketoconazole was coadministered, but the differences were not statistically
      significant. In conclusion, CYP3A plays a relatively minor role in amitriptyline
      clearance in vivo, which is consistent with in vitro predictions using the RAF
      approach.

PMID- 11583472
TI  - Effects of low-dose pravastatin on plasma levels of lipids and apolipoproteins in
      Japanese type II hyperlipoproteinemic subjects with apolipoprotein E phenotype
      E3/2, E3/3, and E4/3.
AB  - Effects of 12 weeks of treatment with pravastatin at a dose of 20 mg/day were
      compared in subjects with type II hyperlipoproteinemia with apo+(lipoprotein) E
      phenotype E3/2, E3/3, and E4/3. There were no differences in age, body mass
      index, smoking status, complications, or plasma levels of lipids and apoproteins,
      except the higher levels of apo E in E3/2 subjects (n = 11) than in E3/3 subjects
      (n = 84) and E4/3 subjects (n = 28). Plasma levels of low-density lipoprotein
      cholesterol (LDL-C) were reduced by 47% +/- 8% (mean +/- SD) in E3/2 subjects,
      36% +/- 10% in E3/3 subjects, and 26% +/- 12% in E4/3 subjects after 12 weeks of
      treatment with pravastatin (all p < 0.0001). Plasma levels of apo B were
      decreased by 40% +/- 12% in E3/2 subjects, 27% +/- 10% in E3/3 subjects, and 18%
      +/- 14% in E4/3 subjects after 12 weeks of treatment with pravastatin (all p <
      0.0001). The reduction in plasma levels of LDL-C and apo B was most marked in
      E3/2 subjects, next in E3/3 subjects, and smallest in E4/3 subjects. The authors
      conclude that treatment with pravastatin at a dose of 20 mg/day in Japanese
      subjects is equally effective as 40 mg/day in Western subjects, and apo
      Epolymorphism is a factor to determine the efficacy of pravastatin in Japanese
      subjects.

PMID- 11583473
TI  - Seville (sour) orange juice: synephrine content and cardiovascular effects in
      normotensive adults.
AB  - The Seville orange extract Citrus aurantium contains m-synephrine (phenylephrine)
      and octopamine; it causes cardiac disturbances in animals and is used by humans
      for weight loss. Juice from the orange (Seville orange juice [SOJ]) is used to
      "knock out" intestinal cytochrome P450 (CYP) 3A4 in bioavailability studies. The
      purpose of this study was to determine synephrine and octopamine concentrations
      in SOJ and SOJ's cardiovascular effects in normotensive humans. Subjects consumed
      8 ounces of SOJ and water in crossover fashion followed by a repeat ingestion 8
      hours later. Hemodynamic (heart rate; systolic, diastolic, and mean arterial
      pressure) measurements followed. Synephrine and octopamine were determined by
      high-performance liquid chromatography. Hemodynamics did not differ significantly
      between water and SOJ groups. Mean synephrine concentration of SOJ samples was
      56.9 +/- 0.52 microg/ml; octopamine was not detected. SOJ ingestion by
      normotensive subjects is expected to be safe. Individuals with severe
      hypertension, tachyarrhythmias, and narrow-angle glaucoma and monoamine oxidase
      inhibitor recipients should avoid SOJ consumption. Persons taking decongestant
      containing cold preparations should also refrain from SOJ intake.

PMID- 11583474
TI  - The pharmacokinetics of enalapril in children and infants with hypertension.
AB  - Forty children with hypertension between the age of 2 months and 15 years
      received 0.07 to 0.14 mg/kg of enalapril as a single daily dose. Enalapril was
      administered orally as a novel extemporaneous suspension in children younger than
      6 years of age and as tablets in older children. First-dose and steady-state
      pharmacokinetics were estimated in children ages 1 to 24 months, 25 months to < 6
      years, 6 to < 12 years, and 12 to < 16 years. Maximum serum concentrations for
      enalapril occurred approximately 1 hour after administration. Serum
      concentrations of enalaprilat, the active metabolite of enalapril, peaked between
      4 and 6 hours after the first dose and 3 and 4 hours after multiple doses. The
      area under the concentration versus time curve (AUC), adjusted for body surface
      area, did not differ between age groups. Based on comparison of first-dose and
      steady-state AUCs, the accumulation of enalaprilat in children ranged from 1.13-
      to 1.45-fold. For children ages 2 to 15 years, mean urinary recovery of total
      enalaprilat ranged from 58.3% in children ages 6 to < 12 years to 71.4% in
      children ages 12 to < 16 years. Urinary recovery for children ages 2 to < 6 years
      was 66.8%. The mean percentage conversion of enalapril to enalaprilat ranged from
      64.7% for children ages 1 to 24 months to 74.6% for children ages 6 to < 12
      years. The median effective half-life for accumulation ranged from 14.6 hours in
      children ages 12 to < 16 years to 16.3 hours in children ages 6 to < 12 years.
      There were two serious adverse events, neither of which was attributed to
      enalapril or resulted in discontinuation of the study drug. The extemporaneous
      suspension used in this study was tolerated well. The pharmacokinetics of
      enalapril and enalaprilat in hypertensive children ages 2 months to 15 years with
      normal renal function appears to be similar to that previously observed in
      healthy adults.

PMID- 11583475
TI  - Cardiac adverse effects of early dexamethasone treatment in preterm infants: a
      randomized clinical trial.
AB  - This study evaluates the effects of early administration of dexamethasone on left
      ventricle dimensions and their clinical significance in preterm infants. Fifty
      preterm infants with birth weight < or = 1250 g and gestational age < or = 30
      weeks were randomly assigned after 72 hours of life to the dexamethasone group (n
      = 25) or to the control group (n = 25). The treated infants received
      dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg/day
      for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for
      the 7th day). Serial echocardiographic measurements of end systolic
      interventricular septum thickness, end diastolic interventricular septum
      thickness, end systolic left ventricle posterior wall thickness, end diastolic
      left ventricle posterior wall thickness, left ventricle end diastolic diameter,
      and left ventricle end systolic diameter were taken before starting
      dexamethasone, on days 3 and 7 of treatment, 7 days after the interruption of
      treatment, and at the 28th day of life. Five infants of each group were excluded
      by the final analysis because of the lack of a complete cardiac evaluation,
      leaving 20 treated and 20 control infants. Infants receiving dexamethasone had a
      significantly larger increase in mean septal and left posterior wall thickness
      during the treatment and 7 days after the dexamethasone weaning. The mean left
      ventricle diameter of treated infants was significantly lower than that of
      control infants from the 7th day of treatment to the 28th day of life. Four
      neonates (20%) in the dexamethasone group developed left ventricular myocardial
      hypertrophy without left ventricle outflow tract obstruction, showing signs of
      decreased cardiac output and ischemic changes on ECG. The daily fluid intake was
      increased to 200 ml/kg to ensure an adequate preload volume, and the complete
      resolution of left ventricle hypertrophy was obtained within the 2nd to 3rd week
      after dexamethasone weaning. Preterm infants receiving an early (< 96 hours of
      life) short course of dexamethasone develop a left ventricular myocardial
      hypertrophy that can be symptomatic and clinically significant. Preterm infants
      included in future studies with the goal to find the minimum dose and duration of
      dexamethasone treatment should be strictly monitored echocardiographically for
      this side effect.

PMID- 11583476
TI  - Pharmacokinetic-pharmacodynamic modeling of rivastigmine, a cholinesterase
      inhibitor, in patients with Alzheimer's disease.
AB  - Rivastigmine is a cholinersterase inhibitor approved recently for the treatment
      of Alzheimer's disease (AD). The objective of this study is to characterize the
      pharmacokinetics-pharmacodynamics of rivastigmine in patients with AD. Eighteen
      AD patients received doses ranging from 1 to 6 mg bid for about 11 weeks.
      Rivastigmine and its active (major) metabolite (ZNS 114-666, also called NAP 226
      90), plasma, and cerebrospinal fluid (CSF) concentrations were determined
      together with the AChE activity and computerized neuropsychological test battery
      (CNTB) scores. Nonlinear mixed-effects modeling of pharmacokinetic and
      pharmacodynamic data was conducted using NONMEM. Rivastigmine and its metabolite
      exhibited dose-disproportional pharmacokinetics. The apparent clearance and
      volume of distribution (plasma) of rivastigmine were estimated to be 120 L/h and
      236 L, respectively. The relative bioavailability at the 6 mg dose was about
      140%. The metabolite had a clearance of about 100 L/h and a volume of
      distribution of 256 L. The kinetics of the parent and metabolite in CSF showed an
      equilibration half-life of about 0.2 and 0.5 hours, respectively. The metabolite
      levels in CSF correlated very well with the acetylcholinesterase inhibition, with
      a ZNS 114-666 concentration of about 5.4 microg/L required for half-maximal
      inhibition of acetylcholinesterase activity. No statistically significant
      correlation of the CNTB scores with enzyme inhibition, parent or metabolite
      concentration (plasma/CSF), or rivastigmine dose could be established. The PK-PD
      model presented in this study can provide valuable information to optimize the
      drug development of rivastigmine and other related compounds and also in
      rationalizing dosing recommendations.

PMID- 11583477
TI  - Pharmacokinetics and pharmacodynamics of thalidomide in HIV patients treated for
      oral aphthous ulcers: ACTG protocol 251. AIDS Clinical Trials Group.
AB  - Thalidomide has increasing clinical benefits, including the healing of aphthous
      ulcers in patients with HIV. Unfortunately, pharmacological information
      addressing the pharmacokinetics (PK) of this compound in HIV patients is limited.
      Concern exists as to whether thalidomide may alter its own metabolism owing to in
      vitro data previously reported. Furthermore, no information is available defining
      the relationship between drug exposure and clinical response. This study
      evaluated the PK and pharmacodynamics (PD) of thalidomide in patients enrolled in
      AIDS Clinical Trials Group Protocol 251. Study patients had HIV infection and
      oral aphthous ulcers of at least 2 weeks'duration. Pharmacologic studies were
      completed in those subjects randomized to receive active thalidomide at a dose of
      200 mg daily for the 4-week study period. PK studies involving serial sampling
      were carried out in 7 subjects following multiple dosing during study weeks 1 and
      4. In addition, trough measurements were done in 20 subjects during each of the 4
      study weeks to explore the relationship between time-averaged trough values and
      extent of clinical response. All samples were analyzed using a validated HPLC
      method, and parameters were determined using noncompartmental PK analysis.
      Thalidomide oral clearance averaged 0.14 +/- 0.08 and 0.12 +/- 0.05 l/h/kg on
      weeks 1 and 4 (p = 0.72), while the terminal elimination half-life averaged 5.7
      +/- 1.5 and 7.3 +/- 1.7 hours (p = 0.12). The median time-averaged trough value
      for subjects deemed complete responders was 0.60, while the median value for
      noncomplete responders was 0.54. Adjusting for baseline CD4 count and initial
      index ulcer area, no significant effects were observed of increased thalidomide
      levels on response. In summary, this study provides steady-state PK data in HIV
      patients managed with thalidomide and suggests negligible effect of chronic
      dosing on drug clearance (comparing results from weeks 1 and 4). Furthermore,
      variable trough measurements between patients do not directly influence the
      effectiveness of thalidomide for oral aphthous ulcers.

PMID- 11583478
TI  - Pharmacokinetics and tolerability of GW420867X, a nonnucleoside reverse
      transcriptase inhibitor, following single escalating doses in healthy male
      volunteers.
AB  - The aim of the current study was to characterize the pharmacokinetics of
      GW420867X, a new nonnucleoside reverse transcriptase inhibitor, using a single
      escalating dose protocol in healthy volunteers. Four dose levels were
      investigated in sequential order: 300, 600, 900, and 1200 mg, with a ratio of 4:1
      subjects receiving active or placebo treatment, respectively. Following single
      dose administration, GW420867X was readily absorbed with a median time to peak
      concentration of 3 to 5 hours. GW420867X plasma exposure (AUC) was dose
      proportional but variable within the 300 to 1200 mg dose range. Less than dose
      proportional increases were observed for Cmax. The terminal elimination t(1/2)
      was 50 hours, which supports once-daily dosing in future studies. Plasma trough
      concentrations of GW420867X at 24 hours after dosing were many fold greater than
      the in vitro IC50 HIV-1(HXB2) in MT4 cells. GW420867X was generally well
      tolerated following single-dose administration up to 900 mg; increased central
      nervous system-related adverse events were observed at higher doses. GW420867X
      had a favorable pharmacokinetic and safety profile that would enable this drug to
      be explored in future clinical studies with HIV-1 infected patients at doses that
      would provide appropriate safety and efficacy.

PMID- 11583479
TI  - Dose proportionality of oral etoricoxib, a highly selective cyclooxygenase-2
      inhibitor, in healthy volunteers.
AB  - To assess dose proportionality of etoricoxib across the anticipated clinical dose
      range, a single panel of 12 healthy subjects was administered single oral doses
      of etoricoxib of 5, 10, 20, 40, and 120 mg in an open, two-part, five-period
      crossover study. Plasma samples were collected aftereach dose and analyzed for
      etoricoxib concentrations. The pharmacokinetics of etoricoxib appear to be linear
      over the entire dose range examined, from 5 to 120 mg. Etoricoxib was found to be
      well tolerated across the 5 to 120 mg dose range.

PMID- 11583480
TI  - A pharmacokinetic study of intramuscular (i.m.) parecoxib sodium in normal
      subjects.
AB  - A single-center, double-blind, placebo-controlled, randomized study was conducted
      to determine the pharmacokinetics, safety, and tolerability of single, rising
      intramuscular (i.m.) doses and the single maximum tolerated dose of parecoxib
      sodium, a prodrug of the novel COX-2 selective anti-inflammatory analgesic drug
      valdecoxib, in 56 healthy male volunteers, ages 18 to 45 years inclusive. Cohorts
      of up to 6 subjects in each dose schedule were administered either parecoxib
      sodium (1 mg, 2 mg, 5 mg, 10 mg, 20 mg, or 40 mg) or matching placebo. Following
      i.m. administration, serial blood samples for measurement of plasma
      concentrations of parecoxib, valdecoxib, and valdecoxib metabolite (M1) were
      collected at predetermined intervals (from 15 minutes prior to dose and through
      96 hours postdose). Urine collections were obtained for drug assay (from -12 to 0
      hours, 0 to 12 hours, and 12 to 24 hours postdose). After i.m. administration,
      peak plasma concentrations of parecoxib were reached within 15 minutes and then
      declined rapidly as prodrug was converted to the active moiety, valdecoxib.
      Change in plasma concentrations of valdecoxib, which declined more slowly (t(1/2)
      = 5.4-9.9 hours), reflected transformation to several metabolites, one of which
      was the minor active metabolite M1. As measured by the AUC(0-infinity), Cmax, and
      XU(0-24) of valdecoxib, parecoxib sodium demonstrated dose proportionality when
      administered in the range of 1 mg to 40 mg of parecoxib. All single i.m. doses up
      to the maximum of 40 mg of parecoxib, as well as concentrations of up to 20
      mg/ml, were well tolerated.

PMID- 11583482
TI  - The effects of tegaserod (HTF 919) on the pharmacokinetics and pharmacodynamics
      of digoxin in healthy subjects.
AB  - Tegaserod (HTF 919) is a highly specific 5-HT4 receptor partial agonist that
      exhibits promotile activity throughout the gastrointestinal tract and is under
      development for the treatment of functional gastrointestinal motility disorders.
      The present study was designed to assess the effect of multiple doses of
      tegaserod on the single-dose pharmacokinetics and pharmacodynamics of digoxin, a
      commonly prescribed agent for congestive heart failure. The study was an open
      label, randomized, two-period crossover design of 12 healthy subjects. One
      treatment included digoxin treatment alone; the other treatment included a
      combined digoxin and tegaserod treatment. On day 1 of the digoxin treatment
      period, subjects received a single 1 mg oral dose of digoxin. In the combined
      tegaserod/digoxin treatment period, subjects received a single oral dose of 1 mg
      digoxin after 3 days of tegaserod (6 mg bid). After coadministration of
      tegaserod, systemic exposure to digoxin was decreased; mean AUC decreased by
      11.9% (p < 0.05) relative to digoxin alone. Cmax was decreased by about 15% (p <
      0.05). The 0.5-hour difference in the median tmax between the two treatments was
      not statistically significant. Because the steady-state trough concentration of
      digoxin (C(SS,min)) correlates with pharmacological effects, C(SS,min) for
      digoxin alone and in combination with tegaserod was simulated based on both
      parametric compartmental modeling and nonparametric superpositioning approaches.
      The predicted arithmetic mean C(SS,min) for combination therapy is 86% to 89% of
      that following digoxin alone. Likewise, the predicted arithmetic mean steady
      state peak concentration (C(SS,min)) and AUC at steady state during a dosing
      interval (AUC(SS,tau)) have a similar decrease. This extent of decrease in
      systemic exposure of digoxin at steady state is unlikely to be clinically
      relevant. Administration of tegaserod (6 mg bid) was well tolerated, both alone
      and in combination with a single dose of digoxin. There were no pharmacodynamic
      changes in ventricular rate and QT interval following coadministration of
      tegaserod with digoxin. The 1.5-hour and 2-hour postdose plasma concentrations of
      tegaserod on days 3 and 4 confirmed adequate exposure. In conclusion, dose
      adjustment for digoxin is unlikely to be needed when tegaserod is coadministered.

PMID- 11583481
TI  - Lack of pharmacokinetic interaction between rofecoxib and methotrexate in
      rheumatoid arthritis patients.
AB  - Rofecoxib is a highly selective and potent inhibitor of cyclooxgenase-2 (COX-2).
      Methotrexate is a disease-modifying agent with a narrow therapeutic index
      frequently prescribed for the management of rheumatoid arthritis. The objective
      of this study was to investigate the influence of clinical doses of rofecoxib on
      the pharmacokinetics of methotrexate in patients with rheumatoid arthritis. This
      was a randomized, double-blind, placebo-controlled study in 25 rheumatoid
      arthritis patients on stable doses of methotrexate. Patients received oral
      methotrexate (7.5 to 20 mg) on days -1, 7, 14, and 21. Nineteen patients received
      rofecoxib 12.5, 25, and 50 mg once daily on days 1 to 7, 8 to 14, and 15 to 21,
      respectively. Six patients received placebo on days 1 to 21 only to maintain a
      double-blinded design for assessment of adverse experiences. Plasma and urine
      samples were analyzed for methotrexate and its major although inactive
      metabolite, 7-hydroxymethotrexate. The AUC(0-infinity) geometric mean ratios
      (GMR) and their 90% confidence intervals (90% CI) (rofecoxib +
      methotrexate/methotrexate alone) for day 7/day -1, day 14/day -1, and day 21/day 
      1, for rofecoxib 12.5, 25, and 50 mg, were 1.03 (0.93, 1.14), 1.02 (0.92, 1.12),
      and 1.06 (0.96, 1.17), respectively (p > 0.2 for all comparisons to day -1). All
      AUC(0-infinity), GMR and Cmax GMR 90% CIs fell within the predefined
      comparability limits of (0.80, 1.25). Similar results were observed for renal
      clearance of methotrexate and 7-hydroxymethotrexate at the highest dose of
      rofecoxib tested (50 mg). It was concluded that rofecoxib at doses of 12.5, 25,
      and 50 mg once daily has no effect on the plasma concentrations or renal
      clearance (tested at the highest dose of rofecoxib) of methotrexate in rheumatoid
      arthritis patients.

PMID- 11583483
TI  - Nonimmune risk factors for chronic renal allograft disfunction.

PMID- 11583484
TI  - Immunologic risk factors for chronic renal allograft dysfunction.
AB  - Tissue injury is probably the central feature leading to CRAD, whether that
      injury is produced by immunological or nonimmunological factors. Tissue injury
      may expose cryptic antigens that, in an allogeneic situation, stimulate immune
      responses that further increase tissue damage. With acute rejection the
      immunological factor most strongly predictive of CRAD, HLA mismatches may
      facilitate rejection or otherwise lead to CRAD. However, clinical studies have
      not always demonstrated an increasing risk of CRAD with increased numbers of HLA
      mismatches. Antibodies produced against HLA or other donor-specific antigens may
      play a role in initiating the CRAD process or may occur secondary to tissue
      damage. Several human transplant studies have demonstrated an association between
      anti-HLA or anti-B cell antibodies and CRAD. In animal models of CRAD, antibodies
      are produced against antigens associated with glomerular and tubular basement
      membranes and mesangial cells, as well as antigens associated with vascular
      endothelial cells. The pathogenetic significance of these antibody responses is
      unclear at this time, but these responses may interfere with repair processes
      that follow tissue injury or otherwise facilitate mechanisms leading to CRAD.
      Whether similar antibody responses against components of basement membrane and
      mesangial cells occur in human renal transplant patients with CRAD is not yet
      known. The most effective way to prevent CRAD is to prevent tissue damage,
      especially immunity-related injury that involves maintaining appropriate
      immunosuppression. When using calcineurin inhibitors for immunosuppression, there
      is a risk of chronic calcineurin inhibitor-associated nephrotoxicity.
      Nonnephrotoxic immunosuppressive agents, such as sirolimus and mycophenolate
      mofetil, may be considered in therapeutic strategies designed to prevent acute
      rejection and to minimize renal tissue damage due to nephrotoxic drugs.

PMID- 11583485
TI  - Viral infections and their impact on chronic renal allograft dysfunction.
AB  - Viral infections, particularly those involving HCMV, are an important
      complication of renal transplantation. Transplantation protocols and treatment
      regimens that increase HCMV infection and disease may promote the development of
      CRAD and impair long-term renal allograft survival. Investigators are beginning
      to illuminate the mechanisms by which HCMV infection may cause chronic rejection
      in general and transplant vascular sclerosis in particular. Migration and
      proliferation of SMCs within the intimal layer of blood vessels is an important
      component of transplant vascular sclerosis, and HCMV appears to facilitate both
      of these processes. Current management strategies for HCMV focus on prevention,
      either using a focal preemptive therapeutic approach or by administering
      antiviral therapies to all or at-risk patients.

PMID- 11583486
TI  - Histopathology of chronic renal allograft dysfunction.

PMID- 11583487
TI  - Vascular and cellular mechanisms of chronic renal allograft dysfunction.

PMID- 11583488
TI  - Exploring treatment options in renal transplantation: the problems of chronic
      allograft dysfunction and drug-related nephrotoxicity.
AB  - The immunosuppressive benefits of cyclosporine and tacrolimus in short-term and
      medium-term renal allograft survival are well documented. It is becoming
      increasingly clear that the basis of this immunosuppression, the inhibition of
      calcineurin, may be linked with nephrotoxicity, hypertension, hyperlipidemia, and
      new-onset diabetes mellitus, side effects that may lead to CRAD, death due to
      CVD, and late renal allograft loss. This clinical picture presents a clear need
      for new strategies that produce adequate immunosuppression to prevent acute
      rejection while simultaneously reducing the side effects associated with CNI
      related therapies. Sirolimus combined with cyclosporine and tacrolimus has
      demonstrated an ability to reduce incidences of early acute rejection and, used
      as base therapy, has provided protection against acute rejection equivalent to
      that of cyclosporine, without the consequent nephrotoxicity associated with CNIs.
      In preliminary results from an ongoing clinical trial, sirolimus has been used to
      eliminate cyclosporine during maintenance immunosuppression, with subsequent
      improvements in measures of blood pressure and renal function. In addition, the
      antiproliferative properties of sirolimus and its ability to prevent graft
      vascular disease in animal studies make sirolimus a promising agent to decrease
      incidences of CRAD and improve long-term renal allograft survival. These findings
      point to a clear need to further explore both the efficacy of sirolimus
      immunotherapy and its long-term effects.

PMID- 11583489
TI  - Causes of late renal allograft loss: chronic allograft dysfunction, death, and
      other factors.
AB  - CAN and patient death with allograft function are the 2 major causes of renal
      allograft loss after the first year, accounting for 80% or more of cases.
      According to current estimates from the United Network for Organ Sharing (UNOS),
      the half-lives for renal allografts performed in 1995 and 1996 from living and
      cadaveric donors are 15.3 and 10.4 years, respectively (2). Consequently, much
      attention has been focused on better understanding the causes of CAN and patient
      death with a functioning allograft in an attempt to improve long-term renal
      allograft outcomes. Although the pathogenesis of CAN is not completely
      understood, we know that CAN involves alloantigen-dependent and alloantigen
      independent factors that combine to produce chronic deterioration of renal
      allograft function. CVD is the most frequent cause of death in renal transplant
      recipients, and we need to address its well-established risk factors in that
      population. Among other improvements, changes in current immunosuppressive
      protocols may increase long-term renal allograft survival and function by
      decreasing both the risk of CAN and the risk of CVD.

PMID- 11583490
TI  - Potential therapeutic interventions to avoid or treat chronic allograft
      dysfunction.
AB  - Despite the significant improvements that have occurred since the introduction of
      CsA, long-term renal allograft survival continues to be an area of concern.
      Management strategies that involve the use of sirolimus offer some promise. A
      number of observations suggest that sirolimus may have the ability to reduce the
      rates or slow the progression of chronic nephropathy. First, sirolimus has been
      shown to inhibit growth-factor-driven proliferation of endothelial and smooth
      muscle cells in vitro (55, 56). Sirolimus also disrupts signal transduction by a
      variety of other cytokines such as EGF and PDGE This is significant because
      cytokine- and growth-factor-stimulated proliferation of endothelial cells, smooth
      muscle cells, parenchymal cells, and fibroblasts appears to underlie the
      development of chronic nephropathy (see Fellstrom, this supplement). Second,
      sirolimus has been demonstrated in various animal models to inhibit the arterial
      intimal thickening that typically follows alloimmune or mechanical injury (56-60;
      see Morris, this supplement). This transplant vasculopathy is a prominent feature
      in chronic rejection of other organ transplants. Moreover, at least 1 published
      study has suggested that sirolimus may be able to stabilize and possibly reverse
      chronic graft vascular disease (61). However, the relative doses of sirolimus
      used in these animal studies have been higher than those used in humans, so the
      relationship of these effects to the clinical setting needs to be further studied
      to define the relevance of these findings. Third, sirolimus, used in combination
      with CsA, reduces the incidence of acute rejection episodes in humans, one of the
      most significant predictors of shortened renal allograft survival (62, 63). Thus,
      an effect of sirolimus to reduce acute rejection episodes or delay their onset is
      expected to reduce renal allograft loss. Furthermore, clinical trials suggest
      that sirolimus treatment may allow dose reductions of CsA or a delay in inception
      of CsA therapy, which might reduce the acute and chronic nephrotoxicity
      associated with CsA and other CNIs. Since nephrotoxicity may promote or aggravate
      renal injury and appears to be common in chronic nephropathy (see Fellstrom and
      Paul, this supplement), reduced exposure to CNIs may translate into reduced rates
      of chronic renal allograft dysfunction. There are no currently effective
      therapies for chronic nephropathy, which is a common cause of late renal
      allograft loss. Preliminary evidence suggests that sirolimus may eventually prove
      useful as prophylaxis of or treatment for chronic nephropathy. Thus, sirolimus
      has come to be regarded as the foundation for maintenance immunosuppressive
      regimens.

PMID- 11583491
TI  - Tumescent steroid infiltration to reduce postoperative swelling after
      craniofacial surgery.
AB  - Steroids are often administered to paediatric craniomaxillofacial patients
      perioperatively to reduce postoperative facial swelling, although there is little
      evidence of their efficacy. Preoperative tumescent infiltration using 7 ml x kg(
      1) of a solution consisting of 0.1 mg x ml(-1) triamcinolone acetate, 0.0125%
      bupivacaine, 0.025% lignocaine, 3 units x ml(-1) hyaluronidase and 1:1000000
      adrenaline in Hartmann's solution was evaluated from a retrospective case
      controlled study of patients undergoing standard fronto-orbital remodelling for
      simple craniosynostosis (n = 20). Eye closure (i.e. inability to open the eyes)
      was used as a marker for severe facial swelling. Patients receiving the tumescent
      infiltration demonstrated significantly less eye closure (P < 0.005), implying
      that the tumescent infiltration had a significant effect on facial swelling. The
      avoidance of eye closure allowed more effective monitoring for neurological and
      ophthalmological complications, which is a significant clinical benefit. The
      infiltration solution has the advantage of a lower corticosteroid dose than
      previously reported dexamethasone-based perioperative regimens, thereby
      minimising any unwanted metabolic effects. The technique is advocated for the
      reduction of postoperative facial swelling in craniomaxillofacial surgical
      patients.

PMID- 11583492
TI  - Meningomyelocele reconstruction with bilobed flaps.
AB  - A new method for the repair of meningomyeloceles is described. After
      neurosurgical repair and closure of the placode, the soft-tissue deficit is
      closed using a bilobed flap. The flap is based superiorly and laterally to the
      area to be covered. The first lobe crosses the midline above the defect, and the
      second lobe goes up the midline perpendicular to the first lobe. Once in place,
      the flap provides a tension-free repair; no suture lines overlie the cord
      closure.

PMID- 11583493
TI  - Firm elevation of the auricle in reconstruction of microtia with a retroauricular
      fascial flap wrapping an autogenous cartilage wedge.
AB  - During conventional reconstruction of the auricle in patients with microtia,
      simply separating the auricle from the mastoid region with a full-thickness skin
      graft usually fails to create firm elevation and sufficient projection. To
      achieve frontal symmetry is difficult, and sometimes the normal auricle needs to
      be set back. We reconstructed the auricle in patients with microtia in two major
      stages using a modified Nagata's method. Using a wide W-incision skin flap, the
      first stage includes implantation of a cartilage framework and transposition of
      the ear lobule. Our modification lies in the second stage. Instead of using the
      superficial temporoparietal fascial flap, we elevated a retroauricular fascial
      flap from the mastoid region, turning it over to wrap an autogenous costal
      cartilage wedge, and covered it with a full-thickness skin graft. Between June
      1996 and May 1999, eight patients underwent this operation. All the fascial flaps
      and overlying full-thickness skin grafts survived well. The advantages of our
      technique include firm elevation, good frontal projection and a natural
      appearance of the posterior aspect of the ear. Additionally, by using this fast
      and practical procedure, we avoid creating additional scars on the scalp and
      preserve the superficial temporoparietal fascia and superficial temporal vessels.

PMID- 11583494
TI  - Closed anterior scoring for prominent-ear correction revisited.
AB  - The closed-anterior-scoring technique has been used over the past 3 years to
      correct 56 prominent ears in 32 patients at the West Midlands Regional Plastic
      Surgery Unit at Wordsley Hospital. A review was carried out to assess the result
      of this surgical procedure. We briefly discuss the historical development of
      other surgical techniques for prominent-ear correction, and describe in detail
      the operative technique for this procedure, which includes closed scoring and
      suturing of the cartilage. We used this technique to treat 24 patients with
      bilateral prominent ears and eight patients with unilateral prominent ears. The
      series comprised 20 females and 12 males, 26 children and six adults. The age
      range was from 4 to 24 years old. There were two complications (an upper-pole
      recurrence and protrusion of a buried prolene suture). Patients were followed up
      for between 6 months and 3 years (mean: 1.5 years). This procedure is quick and
      technically easy to learn, with no anterior scars or posterior cartilage overlap.
      Minimal dissection is involved, leading to a low rate of complications. The
      learning curve is rapid; this paper represents the experience of a specialist
      trainee (SST) after he was taught the technique by the senior author.

PMID- 11583495
TI  - Correction of cleft lip nasal deformity in Orientals using a refined reverse-U
      incision and V-Y plasty.
AB  - A total of 45 patients with cleft lip nasal deformities were operated on between
      September 1997 and December 1999. We reviewed 35 of them. Out of these, 31
      patients had unilateral cleft lip nasal deformities and four patients had
      bilateral cleft lip nasal deformities. The age range of the patients was from 3
      years to 56 years. A reverse-U incision with V-Y plasty was used in 20 patients
      with mild to moderate unilateral cleft lip nasal deformities. An open rhinoplasty
      incision combined with the reverse-U incision and V-Y plasty was used in 11
      patients with severe unilateral cleft lip nasal deformities. A bilateral reverse
      U incision and a trans-columellar incision were used in the four patients with
      bilateral cleft lip nasal deformities. After advancement of the mucochondrial
      flap, alar transfixion sutures were used to ensure firm contact between the nasal
      skin and the redraped reverse-U flap. A composite graft for columellar
      lengthening was used in six cases of severe unilateral cleft lip nasal deformity
      and the four cases of bilateral cleft lip nasal deformity. Ancillary procedures
      included correction of a lateral displacement of the alar base, lip scar
      revision, a cartilage graft for tip augmentation, iliac bone grafting for
      correction of hypoplasia of the maxilla or for an alveolar cleft and corrective
      rhinoplasty. A self-made nasal retainer was applied for 6 months in all patients
      to maintain the corrected contour of the nostril. The follow-up period ranged
      from 11 months to 26 months, with an average of 18 months. The final results were
      evaluated based on the degree of symmetry of the nostrils, the redraping of the
      alar-columellar web and the exposure of the nostrils. Good results were obtained
      in 29 patients where alar-columellar web deformities were either absent or
      minimal and a satisfactory symmetry of the nostrils was achieved. Four patients
      had fair results and two patients had poor results. In conclusion, we suggest
      that the reverse-U incision with V-Y plasty is a useful method for achieving
      symmetry of the nostrils in cleft lip nasal deformities in Orientals. In
      addition, this technique provides ample advancement and repositioning of the
      mucochondrial flap and simultaneous correction of the nasal vestibular web.

PMID- 11583497
TI  - Horseshoe expanded scapular free flap shows no venous congestion.
AB  - The free scapular flap is a reliable solution when a relatively thin cutaneous
      flap is required, but its dimensions limit its use in large defects. The pre
      transfer expansion of the flap has extended its clinical applications, but
      problems still occur. Distal marginal venous congestion and subsequent partial
      necrosis of the flap can occur during the conventional round-shaped expansion of
      the flap. Here, we present a new pattern of flap pre-expansion: the 'horseshoe'
      shaped expansion. The main indications for this procedure and the surgical
      details are described. Advantages and disadvantages over the conventional
      expanded free scapular flap are discussed.

PMID- 11583496
TI  - Activation of coagulation and fibrinolysis in microsurgical reconstructions in
      the lower extremities.
AB  - Coagulation and fibrinolysis activities in relation to trauma, surgery and
      thrombosed microanastomoses were studied during free-flap surgery in eight
      patients with lower-extremity defects due to recent trauma or chronic ulcers. One
      patient had an intraoperative thrombosis, and three more patients required
      reoperations on the same day due to postoperative thromboses; one of these also
      required a second reoperation due to flap failure. The baseline level of
      fibrinogen was slightly elevated in all patients except one, and was
      significantly higher in the patients who underwent reoperation. At the end of the
      primary surgery, distinct thrombin generation (TAT and F1+2) was seen in three
      patients with excessive bleeding, and all three later underwent reoperations. One
      of these patients generated excessive thrombin on the eighth postoperative day,
      upon removal of a necrotic flap. Thrombin generation (F1+2) was also seen at
      baseline in the patient with the intraoperative thrombosis, and persisted on the
      first postoperative day. D-dimer at baseline was higher in patients with recent
      trauma, and in two of these, both of whom underwent reoperations on the same day,
      D-dimer remained high perioperatively. Resistance to fibrinolysis with increased
      PAI-1 levels was seen in these two patients at the time of reoperation. In all,
      TAT and F1+2 were associated with the threat of flap failure. A preoperative
      hypercoagulable state and excessive bleeding during the operation were predictors
      of reoperation. The markers for coagulation and fibrinolysis could be used
      preoperatively to target antithrombotic control, and postoperatively to detect
      the threat of flap failure. Meticulous haemostasis during surgery might help to
      diminish the need for reoperations.

PMID- 11583498
TI  - Home inflation of tissue expanders: a safe and reliable alternative.
AB  - The concept of tissue expansion by the placement of inflatable subcutaneous
      silicone implants was popularised by Radovan in the late 1970s and is now widely
      used in clinical practice. After the initial placement of the expander, a series
      of outpatient visits is required during which the expander is serially inflated.
      These visits can be very stressful for the patient and are costly in terms of
      patient transport and clinic time. We present a series of 26 expanders (in eight
      patients) that were inflated at home by the patient or a relative, and compare
      the results with those from 30 expanders (in 15 patients) inflated in the
      outpatient department. The results show that whilst there was a slightly higher
      incidence of minor infections in the group inflated at home (42% versus 23%, P>
      0.05), the overall success rate of the operation was greater in the home
      inflation group (96% versus 90%, P> 0.05). However, these differences were not
      statistically significant. This study provides evidence to support the practice
      of inflation at home, which is safe, cost effective and less stressful for the
      patient.

PMID- 11583499
TI  - Clinical application of the reversed pedicled venous flap containing perivenous
      areolar tissue and/or nerve in the hand.
AB  - A reversed pedicled venous flap containing perivenous areolar tissue and/or nerve
      was used to cover traumatic skin defects of seven fingers in six patients. The
      series consisted of six men, ranging in age from 20 to 57 years (average: 39
      years). The reconstructed sites were four dorsal skin defects and three volar
      skin defects of the finger. The flap was designed on the dorsum of the hand, in
      such a way as to place a vein at the centre of the flap and not to involve the
      dorsal metacarpal artery. The flap contained a dorsal vein, perivenous areolar
      tissue and fascia of the interosseous muscle. Cutaneous nerves were present in
      three of the seven flaps. The pedicle of the flap was dissected distally to the
      finger web space and the flap was transferred to the skin defect. The size of the
      flap ranged from 1.4x4.5 cm to 6.0x7.0 cm. The average length of the pedicle was
      1.6 cm. Skin grafting was needed at the donor site in one case (flap size:
      6.0x7.0 cm), but primary closure was possible in the remaining cases.
      Postoperatively, the largest flap showed superficial necrosis, although it
      survived. The remaining flaps survived completely. This suggests that in a large
      flap the skin should be attached to the pedicle to prevent congestion. The flap
      can be elevated without reference to the dorsal metacarpal artery at the ulnar
      side of the dorsum of the hand. The flap is an effective option to reconstruct
      skin defects of the finger, especially the little finger.

PMID- 11583500
TI  - Pre-arterialisation of the arterialised venous flap: an experimental study in the
      rat.
AB  - Arteriovenous fistulae cause haemodynamic and morphological changes to the local
      venous channels. We have used the concept of preformed arteriovenous fistulae to
      study the viability improvement of arterialised venous flaps. Five groups of
      flaps were created using the abdominal skin of the Wistar rat (n= 10 in each
      group) with a silastic sheet implanted underneath. Group 1 (control) contained a
      flap without a vascular supply, group 2 (venous perfusion flap) contained a
      single pedicled skeletonised vein and a draining vein, and group 3 (arterialised
      venous flap) contained an arteriovenous shunt proximal to the single pedicled
      skeletonised vein and a draining vein; in group 4 (7 day pre-arterialised flap)
      the arteriovenous shunt was performed 7 days before the flap was raised in the
      same procedure as group 3, and in group 5 (14 day pre-arterialised flap) the
      arteriovenous shunt was performed 14 days before the flap was raised. The
      surviving surface areas of the flaps in each group, assessed 7 days after
      raising, were 0%, 22.21%, 54.32%, 62.21% and 97.47%, respectively. There was a
      statistically significant difference in survival between venous perfusion flaps
      and arterialised venous flaps (P= 0.05). Only the 14 day pre-arterialised flaps
      had a statistically significantly larger area of survival than arterialised
      venous flaps (P= 0.05). Microangioarchitecture of the pre-arterialised group,
      studied by the microvascular corrosion-cast technique combined with scanning
      electron microscopy and transmission electron microscopy, revealed dilatation of
      veins, numerous small neo-vessels and a decrease in or total absence of
      functioning valves. We conclude that 14-day pre-arterialisation in the rat model
      improved the survival of arterialised venous flaps by increasing collateral
      pathways for arterialised blood flow through the flap.

PMID- 11583501
TI  - Subungual squamous cell carcinoma.
AB  - Squamous cell carcinoma of the nail bed is quite uncommon and usually mimics a
      variety of diseases, in particular fungal infection. The possibility of
      malignancy must be considered and a high index of suspicion and early biopsy for
      histology are recommended.

PMID- 11583502
TI  - Experience with difficult keloids.
AB  - A large number of treatment modalities have been used to treat keloid scars, with
      varying degrees of success. A modified combination therapy consisting of
      cryotherapy and intralesional triamcinolone injection has given good results in
      43 patients, with complete resolution in 28% and significant improvement in 44%.
      We find it particularly useful for treating recurrent and/or difficult keloids.

PMID- 11583503
TI  - MRI and malignant melanoma of the parotid gland.
AB  - A case is presented highlighting the unusual features and the value of MRI in the
      assessment of metastatic malignant melanoma of the parotid gland.

PMID- 11583504
TI  - An aberrant lymph node containing metastatic melanoma detected by sentinel node
      biopsy.
AB  - The use of sentinel node biopsy in the staging of malignant melanoma has led to
      the identification of lymph nodes outside the described regional basins, so
      called aberrant nodes. We present a case in which such an aberrant sentinel node
      was found to be positive for metastatic disease, and discuss our surgical
      management.

PMID- 11583505
TI  - Combined use of normal mode and Q-switched ruby lasers in the treatment of
      congenital melanocytic naevi.
AB  - Melanocytic naevi are common and they are often removed for cosmetic purposes. In
      recent years, both the normal mode ruby laser and the Q-switched ruby laser have
      been used, either alone or in combination, for the removal of congenital
      melanocytic naevi. However, their success was restricted to partial lightening
      and incomplete histological clearance. We report a new approach, with combined
      use of normal mode and Q-switched ruby lasers, that improves the effectiveness of
      the laser removal of pigmentation in congenital melanocytic naevi.

PMID- 11583506
TI  - Encapsulated fat necrosis: a case of 'thigh mouse'.
AB  - Encapsulated fat necrosis is a rare condition with clinical features that closely
      resemble a lipoma. The aetiology and pathogenesis are not fully understood but
      the condition has a distinctive histological appearance. We describe a case of
      encapsulated fat necrosis that exhibited unusual mobility. The literature is also
      reviewed.

PMID- 11583507
TI  - Mobilisation after skin grafting of pretibial lacerations.

PMID- 11583508
TI  - Superiorly based flap pharyngoplasty: the degree of postoperative 'tubing' and
      its effect on speech.

PMID- 11583509
TI  - The Derriford Appearance Scale (DAS-59).

PMID- 11583510
TI  - Unilateral mydriasis during blepharoplasty.

PMID- 11583511
TI  - Use of the superficial inferior epigastric vein as an interpositional vein graft
      in pedicled TRAM reconstruction.

PMID- 11583512
TI  - The flexor-tendon repair simulator.

PMID- 11583513
TI  - Transparent-film dressing as an aid to flap monitoring.

PMID- 11583514
TI  - An easy method of preparing hands for surgery.

PMID- 11583515
TI  - A useful technique for securing nails: the figure-of-eight suture.

PMID- 11583516
TI  - The Sommerlad pen: its other uses in hand surgery.

PMID- 11583517
TI  - Suction dressings are no substitute for flap cover in acute open fractures.

PMID- 11583518
TI  - A precise method of gold-weight contour shaping for upper-eyelid loading in
      facial palsy.

PMID- 11583519
TI  - New technology for interactive teaching.

PMID- 11583520
TI  - Effective insulation of the cutting diathermy blade.

PMID- 11583521
TI  - The effect of elevation on digital blood pressure.

PMID- 11583523
TI  - Does eye gaze indicate implicit knowledge of false belief? Charting transitions
      in knowledge.
AB  - Three-year-olds sometimes look to the correct location but give an incorrect
      verbal answer in a false belief task. We examined whether correct eye gaze among
      3- to 5-year-old children indexed unconscious knowledge or low confidence
      conscious knowledge. Children "bet" counters on where they thought a story
      character would go. If children were conscious of the knowledge conveyed by their
      eye gaze then they should have bet modestly on their explicit answer (i.e., been
      unsure whether this answer or the answer conveyed through eye direction was
      correct). We found that children bet very highly on the location consistent with
      their explicit answer, suggesting that they were not aware of the knowledge
      conveyed through their eye gaze. This result was supported by a number of
      conditions that showed that betting was a sensitive measure of even small degrees
      of uncertainty. The results shed light on false-belief understanding, the
      implicit-explicit distinction, and transitional knowledge. We argue that the
      transition to a full understanding of false belief is marked by periods of
      implicit knowledge and explicit understanding with low confidence.

PMID- 11583524
TI  - Toddlers' use of metric information and landmarks to reorient.
AB  - Mobile organisms can keep track of spatial location (both their own location and
      that of objects in the environment) using either an external referent system or
      one centered on the self and updated by information about movement through space.
      When the latter system is disabled (e.g., by rapid turning), aspects of the
      external world must be used to reestablish orientation. Recently, it has been
      claimed that, both for rats and for human toddlers, reorientation is achieved
      using a geometric module that accepts only information about the metric
      properties of the environment (C. R. Gallistel, 1990; L. Hermer & E. S. Spelke,
      1994, 1996). In a series of experiments, this paper confirms that geometric
      information is used for reorientation by young children, but gives reason to
      doubt that the use of this information is achieved using a module impenetrable to
      nongeometric information.

PMID- 11583525
TI  - Perception of voice and tone onset time continua in children with dyslexia with
      and without attention deficit/hyperactivity disorder.
AB  - Tasks assessing perception of a phonemic contrast based on voice onset time (VOT)
      and a nonspeech analog of a VOT contrast using tone onset time (TOT) were
      administered to children (ages 7.5 to 15.9 years) identified as having reading
      disability (RD; n = 21), attention deficit/hyperactivity disorder (ADHD; n = 22),
      comorbid RD and ADHD (n = 26), or no impairment (NI; n = 26). Children with RD,
      whether they had been identified as having ADHD or not, exhibited reduced
      perceptual skills on both tasks as indicated by shallower slopes on category
      labeling functions and reduced accuracy even at the endpoints of the series where
      cues are most salient. Correlations between performance on the VOT task and
      measures of single word decoding and phonemic awareness were significant only in
      the groups without ADHD. These findings suggest that (a) children with RD have
      difficulty in processing speech and nonspeech stimuli containing similar auditory
      temporal cues, (b) phoneme perception is related to phonemic awareness and
      decoding skills, and (c) the potential presence of ADHD needs to be taken into
      account in studies of perception in children with RD.

PMID- 11583526
TI  - Temporal generalization in 3- to 8-year-old children.
AB  - Children aged 3, 5, and 8 years were tested on temporal generalization with
      visual stimuli. Different groups received 4- and 8-s standards. Gradients at all
      ages superimposed when plotted on the same relative scale, indicating underlying
      scalar timing. The principal developmental changes were (i) increasing sharpness
      of the generalization gradient with increasing age and (ii) a change from
      symmetrical (3 and 5 years) to adultlike asymmetrical generalization gradients in
      the oldest children. Theoretical modeling attributed these changes to increasing
      precision of the reference memory of the standard with increasing age, as well as
      a decreased tendency to "misremember" the standard as being shorter than it
      actually was, as the children developed.

PMID- 11583527
TI  - Conceptualization of perceptual attributes: a special case for color?
AB  - Young children experience difficulties establishing conceptual representations of
      color compared with everyday objects. We argue that comparing the development of
      color cognition to that of familiar objects is inappropriate since color is a
      perceptual attribute that can be abstracted from an object and by itself lacks
      functional significance. Instead, we compared the recognition, perceptual
      saliency, and naming of color to that of three other perceptual object attributes
      (motion, form, and size) in 47 children aged 2 to 5 years as a function of
      language age. Results revealed that, although color was perceptually salient
      relative to the other visual attributes, no selective impairment to color
      cognition (recognition and naming) was found relative to the three other visual
      attributes tested. Thus, when the appropriate comparisons are made, we find no
      special delay in the development of color conceptualization. Furthermore, the
      striking disparity between perceptual saliency and cognition of color in our
      youngest age groups suggests that perceptual saliency has little influence on the
      conceptual development of color.

PMID- 11583528
TI  - Multidimensional Fechnerian Scaling: Basics.
AB  - Fechnerian scaling is a theory of how a certain (Fechnerian) metric can be
      computed in a continuous stimulus space of arbitrary dimensionality from the
      shapes of psychometric (discrimination probability) functions taken in small
      vicinities of stimuli at which these functions reach their minima. This theory is
      rigorously derived in this paper from three assumptions about psychometric
      functions: (1) that they are continuous and have single minima around which they
      increase in all directions; (2) that any two stimulus differences from these
      minimum points that correspond to equal rises in discrimination probabilities are
      comeasurable in the small (i.e., asymptotically proportional), with a continuous
      coefficient of proportionality; and (3) that oppositely directed stimulus
      differences from a minimum point that correspond to equal rises in discrimination
      probabilities are equal in the small. A Fechnerian metric derived from these
      assumptions is an internal (or generalized Finsler) metric whose indicatrices are
      asymptotically similar to the horizontal cross-sections of the psychometric
      functions made just above their minima. Copyright 2001 Academic Press. 

PMID- 11583529
TI  - Logical Self-Reference as a Model for Conscious Experience.
AB  - The structure of autoreferential statements that describe (or serve as a logical
      model for) the human conscious experience is analyzed. Autoreferential statements
      are introduced by autoreferential definitions, such as a=F(a, x), where F is a
      Boolean function and x is some atomic statement describing the content of the
      experience, or by analogous systems of inter-related definitions, such as a=F(b,
      x, y) and b=G(a, x, z). It is argued that only "noncreative" (systems of)
      definitions introduce statements that describe conscious experience, the
      noncreativeness meaning that no statement with non-tautological content can be
      derived from these definitions. The structure of such (systems of) definitions is
      comprehensively characterized in a series of theorems. A potential of the model
      in addressing empirical data is illustrated by applying it to the choice between
      two alternatives in the absence of a preference criterion. Copyright 2001
      Academic Press. 

PMID- 11583530
TI  - Directed Convergence in Stable Percept Acquisition.
AB  - We view a perceptual capacity as a nondeductive inference, represented as a
      function from a set of premises to a set of conclusions. The application of the
      function to a single premise to produce a single conclusion is called a "percept"
      or "instantaneous percept." We define a stable percept as a convergent sequence
      of instantaneous percepts. Assuming that the sets of premises and conclusions are
      metric spaces, we introduce a strategy for acquiring stable percepts, called
      directed convergence. We consider probabilistic inferences, where the premise and
      conclusion sets are spaces of probability measures, and in this context we study
      Bayesian probabilistic/recursive inference. In this type of Bayesian inference
      the premises are probability measures, and the prior as well as the posterior is
      updated nontrivially at each iteration. This type of Bayesian inference is
      distinguished from classical Bayesian statistical inference where the prior
      remains fixed, and the posterior evolves by conditioning on successively more
      punctual premises. We indicate how the directed convergence procedure may be
      implemented in the context of Bayesian probabilistic/recursive inference. We
      discuss how the L(infinity) metric can be used to give numerical control of this
      type of Bayesian directed convergence. Copyright 2001 Academic Press. 

PMID- 11583531
TI  - A Comparison of Two Lateral Inhibitory Models of Metacontrast.
AB  - Metacontrast, an apparent reduction in brightness of a target that is followed by
      a non-overlapping mask, has been modeled with simulated neural nets incorporating
      either recurrent lateral inhibition or forward and backward inhibition with
      lateral components. A one-layer lateral inhibitory model (B. Bridgeman, 1971,
      Psychological Review 78, 528-539) and a six-layer model (G. Francis, 1997,
      Psychological Review 104, 572-594) both simulate the basic metacontrast effect,
      showing that stimulus-dependent activity that reverberates for some time in the
      model after stimulus offset is essential to simulate metacontrast. The six-layer
      model does not simulate monotonic masking with low response criterion, an
      essential property of metacontrast; the lateral inhibitory model uses duration of
      reverberation to simulate the criterion. Each model simulates several variations
      of masking, such as changing the relative energy of target and mask, but neither
      can handle effects of practice or attention that apparently engage higher
      processing levels. Copyright 2001 Academic Press. 

PMID- 11583532
TI  - TELEGRAPHIC REVIEWS.

PMID- 11583533
TI  - Switch-over in photochemical reaction mechanism from hydrogen abstraction to
      exciplex-induced quenching: interaction of triplet-excited versus singlet-excited
      acetone versus cumyloxyl radicals with amines.
AB  - The fluorescence and phosphorescence quenching of acetone by 13 aliphatic amines
      has been investigated. The bimolecular rate constants lie in the range of 10(8)
      10(9) M(-1) s(-1) for singlet-excited acetone and 10(6)-10(8) M(-1) s(-1) for the
      triplet case. The rate data indicate that a direct hydrogen abstraction process
      dominates for triplet acetone, while a charge-transfer mechanism, namely,
      exciplex-induced quenching, becomes important for singlet-excited acetone.
      Pronounced stereoelectronic effects toward H abstraction, e.g., for 1,4
      diazabicyclo[2.2.2]octane (DABCO), and significant steric hindrance effects,
      e.g., for N,N-diisopropyl-3-pentylamine, are observed. A negative activation
      energy (E(a) = -0.9 +/- 0.2 kcal mol(-1) for triethylamine and DABCO) and the
      absence of a significant solvent effect on the fluorescence quenching of acetone
      are indicative of the involvement of exciplexes. Full electron transfer can be
      ruled out on the basis of the low reduction potential of acetone, which was found
      to lie below -3.0 V versus SCE. The participation of H abstraction for triplet
      acetone is corroborated by the respective quenching rate constants, which
      resemble the reaction rate constants for cumyloxyl radicals. The latter were
      measured for all 13 amines and showed also a dependence on the electron donor
      properties of the amines. It is suggested that the H abstraction proceeds
      directly and not through an exciplex or ion pair. Further, abstraction from N-H
      bonds in addition to alpha C-H bonds has been corroborated as a significant
      pathway for excited acetone. Product studies and quantum yields for
      photoreduction of singlet- and triplet-excited acetone by triethylamine (8% for
      S(1) versus 24% for T(1)) are in line with the suggested mechanisms of quenching
      through an exciplex and photoreduction through direct H abstraction.

PMID- 11583534
TI  - Enantioconvergent synthesis by sequential asymmetric Horner-Wadsworth-Emmons and
      palladium-catalyzed allylic substitution reactions.
AB  - A new method for enantioconvergent synthesis has been developed. The strategy
      relies on the combination of an asymmetric Horner-Wadsworth-Emmons (HWE) reaction
      and a palladium-catalyzed allylic substitution. Different alpha-oxygen
      substituted, racemic aldehydes were initially transformed by asymmetric HWE
      reactions into mixtures of two major alpha,beta-unsaturated esters, possessing
      opposite configurations at their allylic stereocenters as well as opposite alkene
      geometry. Subsequently, these isomeric mixtures of alkenes could be subjected to
      palladium-catalyzed allylic substitution reactions with carbon, nitrogen, and
      oxygen nucleophiles. In this latter step, the respective (E) and (Z) alkene
      substrate isomers were observed to react with opposite stereospecificity: the (E)
      alkene reacted with retention and the (Z) alkene with inversion of
      stereochemistry with respect to both the allylic stereocenter and the alkene
      geometry. Thus, a single gamma-substituted ester was obtained as the overall
      product, in high isomeric purity. The method was applied to a synthesis of a
      subunit of the iejimalides, a group of cytotoxic macrolides.

PMID- 11583535
TI  - Amphiphilic diblock dendrimers: synthesis and incorporation in Langmuir and
      Langmuir-Blodgett films.
AB  - A new dendron with peripheral long alkyl chains and containing five C(60) units
      in the branching shell has been prepared and attached to a Frechet-type dendron
      functionalized with ethylene glycol chains. The peripheral substitution of the
      resulting globular dendrimer with hydrophobic chains on one hemisphere and
      hydrophilic groups on the other provides the perfect hydrophobic/hydrophilic
      balance allowing the formation of stable Langmuir films. Furthermore, a perfect
      reversibility has been observed in successive compression/decompression cycles.
      The diblock structure of the dendrimer has been also crucial for the efficient
      transfer of the Langmuir films in order to obtain well-ordered multilayered
      Langmuir-Blodgett films. This approach appears particularly interesting since
      functional groups not well adapted for the preparation of Langmuir and Langmuir
      Blodgett films such as fullerenes can be attached into the branching shell of the
      dendritic structure and, thus, efficiently incorporated in thin ordered films.

PMID- 11583536
TI  - Studies on the inactivation of bovine liver enoyl-CoA hydratase by
      (methylenecyclopropyl)formyl-CoA: elucidation of the inactivation mechanism and
      identification of cysteine-114 as the entrapped nucleophile.
AB  - The inhibitory properties of (methylenecyclopropyl)formyl-CoA (MCPF-CoA), a
      metabolite derived from a natural amino acid, (methylenecyclopropyl)glycine,
      against bovine liver enoyl-CoA hydratase (ECH) were characterized. We have
      previously demonstrated that MCPF-CoA specifically targets ECHs, which catalyze
      the reversible hydration of alpha,beta-unsaturated enoyl-CoA substrates to the
      corresponding beta-hydroxyacyl-CoA products. Here, we synthesized (R)- and (S)
      diastereomers of MCPF-CoA to examine the stereoselectivity of this inactivation.
      Both compounds were shown to be competent inhibitors for bovine liver ECH with
      nearly identical second-order inactivation rate constants (k(inact)/K(I)) and
      partition ratios (k(cat)/k(inact)), indicating that the inactivation is
      nonstereospecific with respect to ring cleavage. The inhibitor, upon incubation
      with bovine liver ECH, labels a tryptic peptide, ALGGGXEL, near the active site
      of the protein, where X is the amino acid that is covalently modified. Cloning
      and sequence analysis of bovine liver ECH gene revealed the identity of the amino
      acid residue entrapped by MCPF-CoA as Cys-114 (mature sequence numbering). On the
      basis of gHMQC (gradient heteronuclear multiple quantum coherence) analysis with
      [3-(13)C]-labeled MCPF-CoA, the ring cleavage is most likely induced by the
      nucleophilic attack at the terminal carbon of the exomethylene group (C(2)'). We
      propose a plausible inactivation mechanism that involves relief of ring strain
      and is consistent with examples found in the literature. In addition, these
      studies provide important clues for future design of more efficient and selective
      inhibitors to control and/or regulate fatty acid metabolism.

PMID- 11583537
TI  - NMR studies of Ru(3)(CO)(10)(PMe(2)Ph)(2) and Ru(3)(CO)(10)(PPh(3))(2) and their
      H(2) addition products: detection of new isomers with complex dynamic behavior.
AB  - The clusters Ru(3)(CO)(10)L(2), where L = PMe(2)Ph or PPh(3), are shown by NMR
      spectroscopy to exist in solution in at least three isomeric forms, one with both
      phosphines in the equatorial plane on the same ruthenium center and the others
      with phosphines in the equatorial plane on different ruthenium centers. Isomer
      interconversion for Ru(3)(CO)(10)(PMe(2)Ph)(2) is highly solvent dependent, with
      DeltaH decreasing and DeltaS becoming more negative as the polarity of the
      solvent increases. The stabilities of the isomers and their rates of
      interconversion depend on the phosphine ligand. A mechanism that accounts for
      isomer interchange involving Ru-Ru bond heterolysis is suggested. The products of
      the reaction of Ru(3)(CO)(10)L(2) with hydrogen have been monitored by NMR
      spectroscopy via normal and para hydrogen-enhanced methods. Two hydrogen addition
      products are observed with each containing one bridging and one terminal hydride
      ligand. EXSY spectroscopy reveals that both intra- and interisomer hydride
      exchange occurs on the NMR time scale. On the basis of the evidence available,
      mechanisms for hydride interchange involving Ru-Ru bond heterolysis and CO loss
      are proposed.

PMID- 11583538
TI  - Layer-by-layer assembly of zeolite crystals on glass with polyelectrolytes as
      ionic linkers.
AB  - ZSM-5 crystals and glass plates tethered with trimethylpropylammonium iodide and
      sodium butyrate, respectively, (denoted as Z+, Z-, G+, and G-, respectively) were
      prepared. Treatment of G- with Z+ suspended in ethanol results in monolayer
      assembly of Z+ on G- (G-/Z+) with high surface coverage. The zeolite crystals
      have a strong tendency to closely pack and align with the b-axis normal to the
      glass plate, despite large positive zeta potentials. Subsequent treatment of G
      /Z+ with Z- leads to second-layer assembly of Z- on G-/Z+ (G-/Z+/Z-), but with
      rather poor coverage. Sequential treatment of G+ with poly(sodium 4
      styrenesulfonate)(Na+PSS-), poly(diallyldimethylammonium chloride) (PDDA+Cl-),
      and Na+PSS- followed by Z+ yields glass plates assembled with monolayers of Z+
      with very high surface coverage through the composite polyelectrolyte linkers
      (G+/PSS-/PDDA+/PSS-/Z+). The zeolite crystals also have a strong tendency to
      closely pack and align with the b-axis perpendicular to the substrate plane. The
      binding strength between the zeolite crystals and glass plates is much higher in
      G+/PSS-/PDDA+/PSS-/Z+ than in G-/Z+. Repetition of the sequential PSS-/PDDA+/PSS
      /Z+ layering for five cycles yields glass plates assembled with pentalayers of
      ZSM-5 crystals [G+/(PSS-/PDDA+/PSS-/Z+)(5)]. The observed degrees of coverage and
      alignment of zeolite crystals in each layer were very high up to the third layers
      despite the nonuniformity of the sizes and shapes of the zeolite crystals used in
      this study. This report thus demonstrates the feasibility of layer-by-layer
      assembly of micrometer-sized zeolite crystals on glass through electrostatic
      interaction between surface-bound, full-fledged ionic centers, especially by use
      of polyelectrolyes as the linkers.

PMID- 11583539
TI  - Kinetics and mechanism of the reversible binding of nitric oxide to reduced
      cobalamin B(12r) (Cob(II)alamin).
AB  - The reduced form of aquacobalamin binds nitric oxide very effectively to yield a
      nitrosyl adduct, Cbl(II)-NO. UV-vis, (1)H-, (31)P-, and (15)N NMR data suggest
      that the reaction product under physiological conditions is a six-coordinate,
      "base-on" form of the vitamin with a weakly bound alpha-dimethylbenzimidazole
      base and a bent nitrosyl coordinated to cobalt at the beta-site of the corrin
      ring. The nitrosyl adduct can formally be described as Cbl(III)-NO-. The kinetics
      of the binding and dissociation reactions was investigated by laser flash
      photolysis and stopped-flow techniques, respectively. The activation parameters,
      DeltaH, DeltaS, and DeltaV, for the forward and reverse reactions were estimated
      from the effect of temperature and pressure on the kinetics of these reactions.
      For the "on" reaction of Cbl(II) with NO, the small positive DeltaS and DeltaV
      values suggest the operation of a dissociative interchange (I(d)) substitution
      mechanism at the Co(II) center. Detailed laser flash photolysis and (17)O NMR
      studies provide evidence for the formation of water-bound intermediates in the
      laser flash experiments and strongly support the proposed I(d) mechanism. The
      kinetics of the "off" reaction was studied using an NO-trapping technique. The
      respective activation parameters are also consistent with a dissociative
      interchange mechanism.

PMID- 11583540
TI  - Kinetic intermediates in the folding of gaseous protein ions characterized by
      electron capture dissociation mass spectrometry.
AB  - Alternative mechanisms propose that protein folding in solution proceeds either
      through specific obligate intermediates or by a multiplicity of routes in a
      "folding funnel". These questions are examined in the gas phase by using a new
      method that provides details of the noncovalent binding of solvent-free protein
      ions. Capture of an electron by a multiply charged cation causes immediate
      dissociation (ECD) of a backbone bond, but with negligible excitation of
      noncovalent bonds; thus ECD of a linear protein ion produces two measurable
      fragment ions only if these are not held together by noncovalent bonds. Thermal
      unfolding of 9+ ions of cytochrome c proceeds through the separate unfolding of
      up to 13 backbone regions (represented by 44 bond cleavages) with melting
      temperatures of <26 to 140 degrees C. An 0.25 s laser IR pulse induces unfolding
      of 9+ ions in <4 s in six of these regions, followed by their refolding in 2 min.
      However, for the 15+ ions a laser IR pulse causes slower unfolding through poorly
      defined intermediates that leads to far more ECD products (63% increase in bond
      cleavages) after 1 min, even more than heating to 140 degrees C, with refolding
      to a more compact conformation in 10 min. Random isomerization appears to produce
      a dynamic mixture of conformers that folds through a variety of pathways to the
      most stable conformer(s), consistent with a "folding funnel"; this might also be
      considered as an extension of the classical view to a system with a far smaller
      free energy change yielding multiple conformers. As cautions to inferring
      solution conformational structure from gas-phase data, no structural relationship
      between these gaseous folding intermediates and those in solution is apparent,
      consistent with reduced hydrophobic bonding and increased electrostatic
      repulsion. Further, equilibrium folding of gaseous ions can require minutes, and
      even momentary unfolding of an intermolecular complex during this time can be
      irreversible.

PMID- 11583541
TI  - The RS-.HSR Hydrogen Bond: acidities of alpha,omega-dithiols and electron
      affinities of their monoradicals.
AB  - Gas-phase acidities (deltaGo(acid)) have been measured for 1,2-ethanedithiol, 1,3
      propanedithiol, and 1,4-butanedithiol, using a Fourier transform ion cyclotron
      resonance (FT-ICR) mass spectrometer. Adiabatic electron affinities (EAs) of the
      thiolate monoradicals of these compounds were assigned from electron
      photodetachment spectra of their corresponding thiolate monoanions, acquired
      using a cw-ICR. The dithiols exhibit enhanced acidities (up to 8.7 kcal/mol in
      deltaGo(acid)) and greater EAs (up to 6.7 kcal/mol) than analogous monothiol
      species. These differences are attributed to an intramolecular RS-.HSR hydrogen
      bond in the thiolate anion. Considerations of the RO-.HOR hydrogen bond in
      monoanions of alpha,omega-diols and in the [CH(3)O-.HOCH(3)] complex anion
      suggest that the RS-.HSR hydrogen bond provides up to 9 kcal/mol extra
      stabilization.

PMID- 11583542
TI  - A theoretical study of the dynamic behavior of alkane hydroxylation by a compound
      I model of cytochrome P450.
AB  - Dynamic aspects of alkane hydroxylation mediated by Compound I of cytochrome P450
      are discussed from classical trajectory calculations at the B3LYP level of
      density functional theory. The nuclei of the reacting system are propagated from
      a transition state to a reactant or product direction according to classical
      dynamics on a Born-Oppenheimer potential energy surface. Geometric and energetic
      changes in both low-spin doublet and high-spin quartet states are followed along
      the ethane to ethanol reaction pathway, which is partitioned into two chemical
      steps: the first is the H-atom abstraction from ethane by the iron-oxo species of
      Compound I and the second is the rebound step in which the resultant iron-hydroxo
      complex and the ethyl radical intermediate react to form the ethanol complex.
      Molecular vibrations of the C-H bond being dissociated and the O-H bond being
      formed are significantly activated before and after the transition state,
      respectively, in the H-atom abstraction. The principal reaction coordinate that
      can represent the first chemical step is the C-H distance or the O-H distance
      while other geometric parameters remain almost unchanged. The rebound process
      begins with the iron-hydroxo complex and the ethyl radical intermediate and ends
      with the formation of the ethanol complex, the essential process in this reaction
      being the formation of the C-O bond. The H-O-Fe-C dihedral angle corresponds to
      the principal reaction coordinate for the rebound step. When sufficient kinetic
      energy is supplied to this rotational mode, the rebound process should
      efficiently take place. Trajectory calculations suggest that about 200 fs is
      required for the rebound process under specific initial conditions, in which a
      small amount of kinetic energy (0.1 kcal/mol) is supplied to the transition state
      exactly along the reaction coordinate. An important issue about which normal mode
      of vibration is activated during the hydroxylation reaction is investigated in
      detail from trajectory calculations. A large part of the kinetic energy is
      distributed to the C-H and O-H stretching modes before and after the transition
      state for the H-atom abstraction, respectively, and a small part of the kinetic
      energy is distributed to the Fe-O and Fe-S stretching modes and some
      characteristic modes of the porphyrin ring. The porphyrin marker modes of nu(3)
      and nu(4) that explicitly involve Fe-N stretching motion are effectively enhanced
      in the hydroxylation reaction. These vibrational modes of the porphyrin ring can
      play an important role in the energy transfer during the enzymatic process.

PMID- 11583543
TI  - A TD-DFT study of the photochemistry of urocanic acid in biologically relevant
      ionic, rotameric, and protomeric forms.
AB  - The photochemistry of Urocanic acid, a chromophore present in human skin and
      linked to photoimmunosuppression and skin cancer, is investigated theoretically
      by means of time-dependent density functional theory. Extensive calculations are
      carried out for different ionic, rotameric, and protomeric forms of both the
      trans and cis form. Inclusion of solvation effects, here accounted for by means
      of a continuum solvent model, are found to be crucial for the correct description
      of the biologically relevant zwitterionic forms of the molecule. For the trans
      zwitterionic form, it is found that the planar form usually assumed in the
      literature is not stable, and that a realistic charge separation cannot be
      achieved in the gas phase. Calculated vertical excitation energies are in
      excellent agreement with available experimental data, with a weakly absorbing n -
      > pi transition around 4.0 eV, and strongly absorbing pi --> pi transitions at
      4.5-4.9 eV. The debated intramolecular hydrogen bond is predicted to have a
      modest impact on the vertical spectra in solution, but improves agreement with
      experiment when included. In general, we also predict that different rotameric
      forms have very similar absorption spectra. In addition, we find a candidate
      absorbing state to link trans-urocanic acid to singlet oxygen production and
      subsequent photoaging of the skin.

PMID- 11583544
TI  - Minimum energy structure of hydridotris(pyrazolyl)borato iridium(V) tetrahydride
      is not a C(3upsilon) capped octahedron.
AB  - Recent synthesis and NMR spectroscopy of neutral Ir(V) complexes hydridotris(3,5
      dimethylpyrazol-1-yl)borato tetrahydride (Tp*IrH(4)) and hydridotris(pyrazol-1
      yl)borato tetrahydride (TpIrH(4)) have been interpreted as supporting face-capped
      octahedral structures (C(3upsilon)) with each of three Ir-H bonds trans to an Ir
      N bond and the fourth hydride capping the IrH(3) face. Here, density functional
      geometry optimizations and coupled cluster calculations on hydridotris(pyrazol-1
      yl)borato iridium tetrahydrogen find that a C(s) edge-bridged octahedral
      tetrahydride structure and a C(1) eta(2)-dihydrogen, dihydride structure are
      local minima and find that the C(3upsilon) structure is a local maximum (second
      order saddle point). Several low energy transition states connecting the local
      minima have been located, and these minima can be used to simulate the
      experimental NMR spectra. A comparison of the experimental infrared spectrum of
      Tp*IrH(4) and the harmonic frequency calculations on the C(s), C(1), and
      C(3upsilon) structures also supports the assignment of the C(s)and C(1)
      structures as the observed ones.

PMID- 11583545
TI  - Optical properties of single-walled 4 A carbon nanotubes.
AB  - Optical properties of a series of finite sized hydrogenated carbon nanotubes with
      the smallest diameter of 4 A are studied systematically. Their absorption spectra
      are calculated with the localized-density-matrix method. The semiempirical MNDO
      parametric method 3 (PM3) Hamiltonian is employed. The finite optical gaps are
      predicted for the infinite long single-walled carbon nanotubes. Strong anisotropy
      characteristics of the dynamic polarizabilities are found for these tubes. The
      calculated results are in good agreement with the recent experimental findings.
      Further the compositions of the dipole-induced excitations are examined by
      projecting the corresponding density matrices onto the Hartree-Fock molecular
      orbital representation. Unlike the larger diameter carbon nanotubes whose
      absorption spectra are insensitive to the tube chiralities, the absorption
      spectra of 4 A single-walled carbon nanotubes depend very much on their
      chiralities. The chirality of the single-walled 4 A carbon nanotubes synthesized
      in the channels of the porous zeolites is thus determined to be (5,0) by
      comparing the calculated and measured absorption spectra.

PMID- 11583546
TI  - Characterization of stereochemistry and molecular conformation using solid-state
      NMR tensors.
AB  - A solid-state NMR technique is described for establishing stereochemistry using
      the natural product terrein as a model compound. This method involves comparison
      of experimental (13)C tensor principal values with ab initio computed values for
      all possible computer-generated stereoisomers. In terrein the relative
      stereochemistry is confirmed by NMR to be 2R*,3S with high statistical
      probability (>99.5%). The proposed approach also simultaneously verifies the
      molecular conformation of the two hydroxy groups in terrein established by X-ray
      data. It is sufficient to use only shift tensor values at carbons 2 and 3, the
      stereocenters, to characterize both the stereochemistry and molecular
      conformations. The solid-state NMR method appears to be especially useful for
      determining relative stereochemistry of compounds or their derivatives that are
      difficult to crystallize.

PMID- 11583547
TI  - Structural characterization of proteins with an attached ATCUN motif by
      paramagnetic relaxation enhancement NMR spectroscopy.
AB  - The use of a short, three-residue Cu(2+)-binding sequence, the ATCUN motif, is
      presented as an approach for extracting long-range distance restraints from
      relaxation enhancement NMR spectroscopy. The ATCUN motif is prepended to the N
      termini of proteins and binds Cu(2+) with a very high affinity. Relaxation rates
      of amide protons in ATCUN-tagged protein in the presence and absence of Cu(2+)
      can be converted into distance restraints and used for structure refinement by
      using a new routine, PMAG, that has been written for the structure calculation
      program CNS. The utility of the approach is demonstrated with an application to
      ATCUN-tagged ubiquitin. Excellent agreement between measured relaxation rates and
      those calculated on the basis of the X-ray structure of the protein have been
      obtained.

PMID- 11583548
TI  - Infrared spectra of cis- and trans-peroxynitrite anion, OONO-, in solid argon.
AB  - The peroxynitrite anion, of vast importance in biochemistry, is formed in vivo
      from the reaction of NO and O(-2). Laser ablation of 10 different metal targets
      with concurrent 7 K codeposition of NO/Ar and O(2)/Ar mixtures gives new metal
      independent infrared bands at 1458.3 and 806.1 cm(-)(1), and at 1433.3 and 983.2
      cm(-1), in addition to known O(-4) and (NO)(-2) absorptions. The new bands are
      not observed with CCl(4) added to capture electrons or in O(2) and NO experiments
      without laser ablation to produce electrons, which identifies new product anions.
      Based on (15)NO and (18)O(2) isotopic shifts, splitting patterns in mixed
      isotopic experiments, and comparison with DFT isotopic frequency calculations,
      the former absorptions are assigned to cis-OONO-, and the latter pair to trans
      OONO-, which are isolated from metal cations trapped elsewhere in the matrix. The
      cis- and trans-peroxynitrite anion isomers are probably formed via the ion
      molecule reaction between O(-2)and NO: the O(-2) anion, made by the capture of
      ablated electrons, is attested by the observation of O(-4). cis- and trans-OONO-
      are reversibly photoisomerized by visible and near-UV radiation. Collisional
      stabilization of the OONO- ion-molecule dimer complex during formation of the
      solid argon matrix appears to be crucial.

PMID- 11583549
TI  - Complicated goings-on in the metal-manipulated ring-opening of cyclobutene.
AB  - Most reported examples of transition metal-mediated pericyclic reactions have
      been shown to proceed by nonpericyclic mechanisms. However, the conversion of
      Fe(CO)(4)-cyclobutenes to Fe(CO)(3)-butadienes and CO is thought to proceed
      through a mechanism involving an electrocyclic ring-opening step. We have
      examined this and possible alternative mechanisms for the parent Fe(CO)(4)
      cyclobutene complex using hybrid HF-DFT calculations. In this system there is an
      inherent preference for a pathway that avoids metal-templated electrocyclic ring
      opening, but the pericyclic pathway is predicted to dominate for more elaborate
      substrates and under certain experimental conditions.

PMID- 11583550
TI  - Site-specific amide hydrogen/deuterium exchange in E. coli thioredoxins measured
      by electrospray ionization mass spectrometry.
AB  - Mass spectrometry as an analytical tool to study protein folding and structure by
      hydrogen/deuterium exchange is a relatively new approach. In this study, site
      specific amide deuterium content was measured in oxidized and reduced E. coli
      thioredoxins by using the b(n) ions in electrospray ionization CID MS/MS
      experiments after 20-s incubation in D(2)O phosphate-buffered solution (pH 5.7).
      The deuterium levels correlated well with reported NMR-determined H/D exchange
      rate constants. The deuterium measured by y(n) ions, however, showed much less
      reliable correlation with rate exchange data. In general, residues in alpha
      helices and beta sheets, when measured by b(n) ions, showed low incorporation of
      deuterium while loops and turns had high deuterium levels. Most amide sites in
      the two protein forms showed similar deuterium levels consistent with the
      expected similarity of their structures, but there were some differences. The
      turn consisting of residues 18-22 in particular showed more variability in
      deuterium content consistent with reported structural differences in the two
      forms. The deuterium uptake by thioredoxins alkylated at Cys-32 by S-(2
      chloroethyl)glutathione and S-(2-chloroethyl)cysteine, in peptides 1-24 and 45
      58, was similar to that observed for oxidized and reduced thioredoxins, but
      several residues, particularly Leu-53 and Thr-54, showed slightly elevated
      deuterium levels, suggesting that structural changes had occurred from alkylation
      of the protein at Cys-32. It is concluded that b(n) ions are reliable for
      determining the extent of site-specific amide hydrogen isotope exchange and that
      mass spectrometry is useful as a complementary technique to NMR and other
      analytical methods for probing regional structural characteristics of proteins.

PMID- 11583551
TI  - Molecular dynamics simulations of the mononuclear zinc-beta-lactamase from
      Bacillus cereus complexed with benzylpenicillin and a quantum chemical study of
      the reaction mechanism.
AB  - Herein, we present results from MD simulations of the Michaelis complex formed
      between the B. cereus zinc-beta-lactamase enzyme and benzylpenicillin. The
      structural and dynamical effects induced by substrate-binding, the specific role
      of the conserved residues, and the near attack conformers of the Michaelis
      complex are discussed. Quantum chemical methods (HF/6-31G* and B3LYP/6-31G*) are
      also applied to study the hydrolysis reaction of N-methylazetidinone catalyzed by
      a monozinc system consisting of the side chains of the histidine residues (His86,
      His88, and His149) complexed with Zn-OH and the side chains of Asp90 and His210.
      From this model system, we built molecular-mechanics representations of the
      prereactive complex and transition state configurations docked into the active
      site. Linear-scaling semiempirical calculations coupled with a continuum solvent
      model were then performed on these static models. We propose that the
      experimental rate data for the B. cereus enzyme is compatible with a one-step
      mechanism for the hydrolysis of beta-lactam substrates in which His210 acts as a
      proton donor.

PMID- 11583552
TI  - Molecular recognition in cyclodextrin complexes of amino acid derivatives. 1.
      Crystallographic studies of beta-cyclodextrin complexes with N-acetyl-L
      phenylalanine methyl ester and N-acetyl-L-phenylalanine amide pseudopeptides.
AB  - Cyclodextrins (CDs) are widely utilized in studies of chiral and molecular
      recognition. By changing the functionality of the guest molecule, the effect of
      such changes on recognition by the host CD molecule can be examined. We report
      crystal structure determinations for two nearly isomorphous complexes of
      phenylalanine derivatives: beta-CD/N-acetyl-L-phenylalanine methyl ester and beta
      CD/N-acetyl-L-phenylalanine amide. The complexes crystallize as hydrated head-to
      head host dimers with two included guest molecules in space group P1. The crystal
      packing is such that it presents a nonconstraining hydrophobic pocket adjacent to
      a hydrophilic region, where potential hydrogen-bonding interactions with hydroxyl
      groups of neighboring cyclodextrin molecules and waters of hydration can occur.
      The two host molecules display very similar conformations; only a few of the
      primary hydroxyl groups are conformationally disordered. There are a number of
      changes in the location of water of hydration molecules, some of which are the
      result of different hydrogen-bonding interactions. For the different guest
      molecules, similar modes of penetration are observed in the CD torus; however,
      there is a 0.985-A shift in the position of the guest molecules in the host
      torus, which takes place without changing the hydrophobic interactions displayed
      by the phenyl side chains. This observation and the thermal motion of the guest
      molecules in the ester complex are taken as evidence that complex binding forces
      are weak. The pseudopeptides experience a significant degree of flexibility in
      the crystalline environment provided by CD dimers. Conformational differences of
      the pseudopeptide backbones and the presence of disordered water molecules in the
      host-guest interface provide examples of different hydrogen-bonding schemes of
      similar potential energy. The crystal system presents an opportunity to establish
      a database of molecular interactions for small peptides and peptide analogues
      with waters of hydration and functional groups in nonconstraining binding
      environments.

PMID- 11583553
TI  - Molecular recognition in cyclodextrin complexes of amino acid derivatives. 2. A
      new perturbation: the room-temperature crystallographic structure determination
      for the N-acetyl-p-methoxy-L-phenylalanine methyl ester/beta-cyclodextrin
      complex.
AB  - Cyclodextrins (CDs) are cyclic oligosaccharides that encapsulate various small
      organic molecules, forming inclusion complexes. Because CD complexes are held
      together purely by noncovalent interactions, they function as excellent models
      for the study of chiral and molecular recognition mechanisms. Recently, room
      temperature crystallographic studies of both the 2:2 N-acetyl-L-phenylalanine
      methyl ester/beta-CD and 2:2 N-acetyl-L-phenylalanine amide/beta-CD complexes
      were reported. The effect of changes in carboxyl backbone functional group on
      molecular recognition by the host CD molecule was examined for the nearly
      isomorphous supramolecular complexes. A new perturbation of the system is now
      examined, specifically perturbation of the aromatic side chain. We report a room
      temperature crystal structure determination for the 2:2 N-acetyl-p-methoxy-L
      phenylalanine methyl ester/beta-CD inclusion complex. The complex crystallizes
      isomorphously with the two previously reported examples in space group P1; the
      asymmetric unit consists of a hydrated head-to-head host dimer with two included
      guest molecules. The crystal packing provides both a nonconstraining extended
      hydrophobic pocket and an adjacent hydrophilic region, where hydrogen-bonding
      interactions can potentially occur with primary hydroxyl groups of neighboring CD
      molecules and waters of hydration. The rigid host molecules show no sign of
      conformational disorder, and water of hydration molecules exhibit the same type
      of disorder observed for the other two complexes, with a few significant
      differences in locations of water molecules in the hydrophilic region near guest
      molecules. There is evidence for modest disorder in the guest region of an
      electron density map. In comparing this system with the two previously reported
      complexes of phenylalanine derivatives, it is found that the packing of the guest
      molecules inside the torus of the CD changes upon substitution of a methoxy group
      at the para position of the aromatic phenyl ring. Backbone hydrogen-bonding
      interactions for the guest molecules with the CD primary hydroxyls and waters
      also change. This structure determination is a new and revealing addition to a
      small but growing database of amino acid and peptidomimetic interactions with
      carbohydrates.

PMID- 11583554
TI  - Photoswitching of intramolecular magnetic interaction using a diarylethene dimer.

PMID- 11583555
TI  - A dual fluorescence temperature sensor based on perylene/exciplex
      interconversion.

PMID- 11583556
TI  - The guanacastepenes: a highly diverse family of secondary metabolites produced by
      an endophytic fungus.

PMID- 11583557
TI  - Aromatic polyethers with low polydispersities from chain-growth polycondensation.

PMID- 11583558
TI  - Bismuth nanotubes: a rational low-temperature synthetic route.

PMID- 11583559
TI  - Complete thermodynamic characterization of reduction and protonation of the bc(1)
      type Rieske [2Fe-2S] center of Thermus thermophilus.

PMID- 11583561
TI  - The facile one-pot synthesis of shell cross-linked micelles in aqueous solution
      at high solids.

PMID- 11583560
TI  - Switching enantiofacial selectivities using one chiral source: catalytic
      enantioselective synthesis of the key intermediate for (20S)-camptothecin family
      by (S)-selective cyanosilylation of ketones.

PMID- 11583562
TI  - Selective catalysis of elementary steps by Asp-99 and Tyr-14 of 3-Oxo-delta(5)
      steroid isomerase.

PMID- 11583563
TI  - Single-molecule magnets: ligand-induced core distortion and multiple Jahn-Teller
      isomerism in [Mn(12)O(12)(O(2)CMe)(8)(O(2)PPh(2))(8)(H(2)O)(4)].

PMID- 11583564
TI  - An efficient chemoenzymatic strategy for the synthesis of wild-type and
      vancomycin-resistant bacterial cell-wall precursors: UDP-N-acetylmuramyl
      peptides.

PMID- 11583565
TI  - Rhodium-catalyzed hydroarylation of alkynes with arylboronic acids: 1,4-shift of
      rhodium from 2-aryl-1-alkenylrhodium to 2-alkenylarylrhodium intermediate.

PMID- 11583566
TI  - Di-pi-methane reactions promoted by SET from electron-donor sensitizers.

PMID- 11583567
TI  - Intermolecular alkyl radical addition to chiral N-acylhydrazones mediated by
      manganese carbonyl.

PMID- 11583568
TI  - Dual-mode X-band EPR study of two isomers of the endohedral metallofullerene
      Er@C(82).

PMID- 11583569
TI  - Evidence for an umbrella mechanism of bilayer transport.

PMID- 11583570
TI  - Congenital disorders of glycosylation type I leads to altered processing of N
      linked glycans, as well as underglycosylation.
AB  - The N-linked glycans on transferrin and alpha(1)-antitrypsin from patients with
      congenital disorders of glycosylation type I have increased fucosylation and
      branching relative to normal controls. The elevated levels of monofucosylated
      biantennary glycans are probably due to increased alpha-(1-->6) fucosylation. The
      presence of bi- and trifucosylated triantennary and tetra-antennary glycans
      indicated that peripheral alpha-(1-->3), as well as core alpha-(1-->6),
      fucosylation is increased. Altered processing was observed on both the fully and
      underglycosylated glycoforms.

PMID- 11583571
TI  - Coactosin-like protein, a human F-actin-binding protein: critical role of lysine
      75.
AB  - Coactosin-like protein (CLP) was recently identified in a yeast two-hybrid screen
      using 5-lipoxygenase as bait. In the present study, we report the functional
      characterization of CLP as a human filamentous actin (F-actin)-binding protein.
      CLP mRNA shows a wide tissue distribution and is predominantly expressed in
      placenta, lung, kidney and peripheral-blood leucocytes. Endogenous CLP is
      localized in the cytosol of myeloid cells. Using a two-hybrid approach, actin was
      identified as a CLP-interacting protein. Binding experiments indicated that CLP
      associates with F-actin, but does not form a stable complex with globular actin.
      In transfected mammalian cells, CLP co-localized with actin stress fibres. CLP
      bound to actin filaments with a stoichiometry of 1:2 (CLP: actin subunits), but
      could be cross-linked to only one subunit of actin. Site-directed mutagenesis
      revealed the involvement of Lys(75) of CLP in actin binding, a residue highly
      conserved in related proteins and supposed to be exposed on the surface of the
      CLP protein. Our results identify CLP as a new human protein that binds F-actin
      in vitro and in vivo, and indicate that Lys(75) is essential for this
      interaction.

PMID- 11583572
TI  - Conformation of heparin pentasaccharide bound to antithrombin III.
AB  - The interaction, in aqueous solution, of the synthetic pentasaccharide AGA*IA(M)
      (GlcN,6-SO(3)alpha 1-4GlcA beta 1-4GlcN,3,6-SO(3)alpha 1-4IdoA,2-SO(3)alpha 1
      4GlcN,6-SO(3)alpha OMe; where GlcN,6-SO(3) is 2-deoxy-2-sulphamino-alpha-D
      glucopyranosyl 6-sulphate, IdoA is l-iduronic acid and IdoA2-SO(3) is L-iduronic
      acid 2-sulphate), which exactly reproduces the structure of the specific binding
      sequence of heparin and heparan sulphate for antithrombin III, has been studied
      by NMR. In the presence of antithrombin there were marked changes in the chemical
      shifts and nuclear Overhauser effects (NOEs), compared with the free state. On
      the basis of the optimized geometry of the pentasaccharide the transferred NOEs
      were interpreted with full relaxation and conformational exchange matrix
      analysis. An analysis of the three-dimensional structures of the pentasaccharide
      in the free state, and in the complex, revealed the binding to be accompanied by
      dihedral angle variation at the A-G and I-A(M) (where G, I, A and A(M) are beta-d
      glucuronic acid, 2-O-sulphated alpha-L-iduronic acid, N,6-O-sulphated alpha-D
      glucosamine and the alpha-methyl-glycoside of A respectively) glycosidic
      linkages. Evidence is also provided that the protein drives the conformation of
      the 2-O-sulphated iduronic acid residue towards the skewed (2)S(0) form.

PMID- 11583573
TI  - Promoter I of the ovine acetyl-CoA carboxylase-alpha gene: an E-box motif at -114
      in the proximal promoter binds upstream stimulatory factor (USF)-1 and USF-2 and
      acts as an insulin-response sequence in differentiating adipocytes.
AB  - Acetyl-CoA carboxylase-alpha (ACC-alpha) plays a central role in co-ordinating de
      novo fatty acid synthesis in animal tissues. We have characterized the regulatory
      region of the ovine ACC-alpha gene. Three promoters, PI, PII and PIII, are
      dispersed throughout 50 kb of genomic DNA. Expression from PI is limited to
      adipose tissue and liver. Sequence comparison of the proximal promoters of ovine
      and mouse PIs demonstrates high nucleotide identity and that they are
      characterized by a TATA box at -29, C/EBP (CCAAT enhancer-binding protein)
      binding motifs and multiple E-box motifs. A 4.3 kb ovine PI-luciferase reporter
      construct is insulin-responsive when transfected into differentiated ovine
      adipocytes, whereas when this construct is transfected into ovine preadipocytes
      and HepG2 cells the construct is inactive and is not inducible by insulin. By
      contrast, transfection of a construct corresponding to 132 bp of the proximal
      promoter linked to a luciferase reporter is active and inducible by insulin in
      all three cell systems. Insulin signalling to the -132 bp construct in
      differentiated ovine adipocytes involves, in part, an E-box motif at -114.
      Upstream stimulatory factor (USF)-1 and USF-2, but not sterol regulatory element
      binding protein 1 (SREBP-1), are major components of protein complexes that bind
      this E-box motif. Activation of the 4.3 kb PI construct in differentiated ovine
      adipocytes is associated with endogenous expression of PI transcripts throughout
      differentiation; PI transcripts are not detectable by RNase-protection assay in
      ovine preadipocytes, HepG2 cells or 3T3-F442A adipocytes. These data indicate the
      presence of repressor motifs in PI that are required to be de-repressed during
      adipocyte differentiation to allow induction of the promoter by insulin.

PMID- 11583574
TI  - RhoGDI-binding-defective mutant of Cdc42Hs targets to membranes and activates
      filopodia formation but does not cycle with the cytosol of mammalian cells.
AB  - We have identified a mutant of the human G-protein Cdc42Hs, R66E, that fails to
      form a detectable complex with the GDP-dissociation inhibitor RhoGDI in cell-free
      systems or in intact cells. This point mutant is prenylated, binds guanine
      nucleotide and interacts with GTPase-activating protein in a manner
      indistinguishable from wild-type Cdc42Hs. Immunofluorescence localization studies
      revealed that this RhoGDI-binding-defective mutant is found predominantly in the
      Golgi apparatus, with a staining pattern similar to that of the wild-type
      protein. However, unlike wild-type Cdc42Hs, which is distributed in both the
      microsomal membrane and cytosolic fractions, studies using differential
      centrifugation show that prenylated R66E Cdc42Hs is found exclusively in
      association with lipid bilayers. Additionally, whereas the overexpression of
      RhoGDI results in an apparent translocation of wild-type Cdc42Hs from the Golgi
      apparatus into the cytosol, identical RhoGDI-overexpression conditions do not
      alter the Golgi localization of the R66E mutant. Furthermore, overexpression of
      this RhoGDI-binding-defective mutant of Cdc42Hs seems to activate redistribution
      of the actin cytoskeleton and filopodia formation in fibroblasts in a manner
      indistinguishable from the wild-type protein. Taken together, these results
      suggest that the interaction of Cdc42Hs with RhoGDI is not essential for proper
      membrane targeting of nascent prenylated Cdc42Hs in mammalian cells; neither is
      this interaction an essential part of the mechanism by which Cdc42Hs activates
      filopodia formation. However, it does seem that redistribution of Cdc42Hs to the
      cytosolic compartment is absolutely dependent on RhoGDI interaction.

PMID- 11583575
TI  - Identification of a novel class of insect glutathione S-transferases involved in
      resistance to DDT in the malaria vector Anopheles gambiae.
AB  - The sequence and cytological location of five Anopheles gambiae glutathione S
      transferase (GST) genes are described. Three of these genes, aggst1-8, aggst1-9
      and aggst1-10, belong to the insect class I family and are located on chromosome
      2R, in close proximity to previously described members of this gene family. The
      remaining two genes, aggst3-1 and aggst3-2, have a low sequence similarity to
      either of the two previously recognized classes of insect GSTs and this prompted
      a re-evaluation of the classification of insect GST enzymes. We provide evidence
      for seven possible classes of insect protein with GST-like subunits. Four of
      these contain sequences with significant similarities to mammalian GSTs. The
      largest novel insect GST class, class III, contains functional GST enzymes
      including two of the A. gambiae GSTs described in this report and GSTs from
      Drosophila melanogaster, Musca domestica, Manduca sexta and Plutella xylostella.
      The genes encoding the class III GST of A. gambiae map to a region of the genome
      on chromosome 3R that contains a major DDT [1,1,1-trichloro-2,2-bis-(p
      chlorophenyl)ethane] resistance gene, suggesting that this gene family is
      involved in GST-based resistance in this important malaria vector. In further
      support of their role in resistance, we show that the mRNA levels of aggst3-2 are
      approx. 5-fold higher in a DDT resistant strain than in the susceptible strain
      and demonstrate that recombinant AgGST3-2 has very high DDT dehydrochlorinase
      activity.

PMID- 11583576
TI  - Metabolism of exogenous sn-1-alkyl-sn-2-lyso-glucosaminyl-phosphatidylinositol in
      HeLa D cells: accumulation of glucosaminyl(acyl)phosphatidylinositol in a
      metabolically inert compartment.
AB  - The somatic genetic defect in paroxysmal nocturnal haemoglobinuria (PNH) involves
      a block in the transfer of GlcNAc from UDP-GlcNAc to phosphatidylinositol (PI),
      the first step in the biosynthetic pathway for glycosylphosphatidylinositols
      (GPIs). We asked whether an exogenous lipid corresponding to an early
      intermediate in this pathway can be taken up by cells in culture and proceed
      through the GPI pathway. This approach could offer a strategy to bypass the block
      in PNH. To address this question we incubated HeLa D cells with sn-1-alkyl-sn-2
      lyso-GlcN-[(3)H]PI (lyso-alkyl-GlcN-[(3)H]PI) for 24 h and analysed the cellular
      lipids. We found three lipid products: unaltered lyso-alkyl-GlcN-[(3)H]PI, GlcN
      [(3)H]PI and GlcN(acyl)[(3)H]PI (GlcN-PI with a fatty acid acyl group on
      inositol). Since the latter two lipids are intermediates in the GPI biosynthetic
      pathway, this observation demonstrates that an exogenous lipid can enter and
      proceed partially through this pathway. However, the conversion of GlcN(acyl)PI
      to downstream mannosylated GPI intermediates in the GPI pathway was inefficient,
      both for GlcN(acyl)PI produced from the exogenous lipid as well as from that
      obtained by metabolic labelling with [(3)H]inositol. We investigated this poor
      conversion by examining whether GlcN(acyl)PI, radioactively labelled sequentially
      by [(14)C]inositol and [(3)H]inositol, resided in one compartment and could be
      readily metabolized to downstream intermediates. Isotope ratios indicated that
      the turnover of GlcN(acyl)PI was slower than those of either downstream
      mannosylated GPIs or even GPI anchors on proteins, the final products of GPI
      pathway. This result is incompatible with the one-compartment model and indicates
      that GlcN(acyl)PI in HeLa D cells accumulates largely in a compartment that is
      inert to subsequent mannosylation.

PMID- 11583577
TI  - Effects of environment on flavin reactivity in morphinone reductase: analysis of
      enzymes displaying differential charge near the N-1 atom and C-2 carbonyl region
      of the active-site flavin.
AB  - The side chain of residue Arg(238) in morphinone reductase (MR) is located close
      to the N-1/C-2 carbonyl region of the flavin isoalloxazine ring. During enzyme
      reduction negative charge develops in this region of the flavin. The positioning
      of a positively charged side chain in the N-1/C-2 carbonyl region of protein
      bound flavin is common to many flavoprotein enzymes. To assess the contribution
      made by Arg(238) in stabilizing the reduced flavin in MR we isolated three mutant
      forms of the enzyme in which the position of the positively charged side chain
      was retracted from the N-1/C-2 carbonyl region (Arg(238)-->Lys), the positive
      charge was removed (Arg(238)-->Met) or the charge was reversed (Arg(238)-->Glu).
      Each mutant enzyme retains flavin in its active site. Potentiometric studies of
      the flavin in the wild-type and mutant forms of MR indicate that the flavin
      semiquinone is not populated to any appreciable extent. Reduction of the flavin
      in each enzyme is best described by a single Nernst function, and the values of
      the midpoint reduction potentials (E(12)) for each enzyme fall within the region
      of -247+/-10 mV. Stopped-flow studies of NADH binding to wild-type and mutant MR
      enzymes reveal differences in the kinetics of formation and decay of an enzyme
      NADH charge-transfer complex, reflecting small perturbations in active-site
      geometry. Reduced rates of hydride transfer in the mutant enzymes are attributed
      to altered geometrical alignment of the nicotinamide coenzyme with FMN rather
      than major perturbations in reduction potential, and this is supported by an
      observed entropy-enthalpy compensation effect on the hydride transfer reaction
      throughout the series of enzymes. The data indicate, in contrast with dogma, that
      the presence of a positively charged side chain close to the N-1/C-2 carbonyl
      region of the flavin in MR is not required to stabilize the reduced flavin. This
      finding may have general implications for flavoenzyme catalysis, since it has
      generally been assumed that positive charge in this region has a stabilizing
      effect on the reduced form of flavin.

PMID- 11583578
TI  - Calmodulin inhibitors trigger the proteolytic processing of membrane type-1
      matrix metalloproteinase, but not its shedding in glioblastoma cells.
AB  - Most transmembrane proteins are subjected to limited proteolysis by cellular
      proteases, and stimulation of cleavage of membrane proteins by calmodulin (CaM)
      inhibitors was recently shown. The present study investigated the ability of
      several CaM inhibitors to induce the proteolytic cleavage of the membrane type-1
      matrix metalloproteinase (MT1-MMP) from the cell surface of highly invasive U-87
      glioblastoma cells. Although no shedding of a soluble MT1-MMP form was induced by
      CaM inhibitors in the conditioned media, we showed that these inhibitors induced
      MT1-MMP proteolytic processing to the 43 kDa membrane-bound inactive form that
      was not correlated with an increase in proMMP-2 activation but rather with an
      increase in tissue inhibitor of MMPs (TIMP)-2 expression levels. Moreover, this
      proteolytic processing was sensitive to marimastat suggesting the involvement of
      MMPs. Interestingly, CaM inhibitors antagonized concanavalin A- and cytochalasin
      D-induced proMMP-2 activation, and affected the cytoskeletal actin organization
      resulting in the loss of migratory potential of U-87 glioblastoma cells.
      Cytoplasmic tail-truncated MT1-MMP constructs expressed in COS-7 cells were also
      affected by CaM inhibitors suggesting that these inhibitors stimulated MT1-MMP
      proteolytic processing by mechanisms independent of the CaM-substrate
      interaction. We also propose that TIMP-2 acts as a negative regulator of MT1-MMP
      dependent activities promoted by the action of CaM inhibitors in U-87
      glioblastoma cells.

PMID- 11583579
TI  - Sphingosine-induced apoptosis is dependent on lysosomal proteases.
AB  - We propose a new mechanism for sphingosine-induced apoptosis, involving
      relocation of lysosomal hydrolases to the cytosol. Owing to its lysosomotropic
      properties, sphingosine, which is also a detergent, especially when protonated,
      accumulates by proton trapping within the acidic vacuolar apparatus, where most
      of its action as a detergent would be exerted. When sphingosine was added in low
      to-moderate concentrations to Jurkat and J774 cells, partial lysosomal rupture
      occurred dose-dependently, starting within a few minutes. This phenomenon
      preceded caspase activation, as well as changes of mitochondrial membrane
      potential. High sphingosine doses rapidly caused extensive lysosomal rupture and
      ensuing necrosis, without antecedent apoptosis or caspase activation. The
      sphingosine effect was prevented by pre-treatment with another, non-toxic,
      lysosomotropic base, ammonium chloride, at 10 mM. The lysosomal protease
      inhibitors, pepstatin A and epoxysuccinyl-L-leucylamido-3-methyl-butane ethyl
      ester ('E-64d'), inhibited markedly sphingosine-induced caspase activity to
      almost the same degree as the general caspase inhibitor benzyloxycarbonyl-Val-Ala
      DL-Asp-fluoromethylketone ('Z-VAD-FMK'), although they did not by themselves
      inhibit caspases. We conclude that cathepsin D and one or more cysteine
      proteases, such as cathepsins B or L, are important mediators of sphingosine
      induced apoptosis, working upstream of the caspase cascade and mitochondrial
      membrane-potential changes.

PMID- 11583580
TI  - Survival-factor-induced phosphorylation of Bad results in its dissociation from
      Bcl-x(L) but not Bcl-2.
AB  - The pro-apoptotic Bcl-2-family protein Bad heterodimerizes with Bcl-2 and Bcl
      x(L) in the outer mitochondrial membranes, nullifying their anti-apoptotic
      activities and promoting cell death. We report that interleukin-3 (IL-3)
      stimulation induces Bad phosphorylation and triggers its translocation from
      mitochondria to cytoplasm in cells expressing Bcl-x(L) but not Bcl-2.
      Overexpression of Bad sensitized Bcl-x(L)-expressing FL5.12 cells to apoptosis
      induced by IL-3 deprivation, but had no effect on the viability of cells
      expressing Bcl-2. IL-3 stimulation induced Bad phosphorylation at Ser-112,
      impairing its binding to Bcl-x(L) and resulting in its association with 14-3-3
      proteins in the cytosol. However, Ser-112 phosphorylation could not trigger Bad
      dissociation from mitochondria in FL5.12 cells expressing Bcl-2. In 293T cells
      expressing Bcl-x(L), Bad was phosphorylated at three serines, 112, 136 and 155,
      and was largely localized in the cytosolic fraction. In contrast, overexpression
      of Bcl-2 prevented phosphorylation of Bad at Ser-136 and Ser-155, sequestering
      this protein in the mitochondrial membranes. When the N-terminal regions of Bcl-2
      and Bcl-x(L) were swapped with each other, the Bcl-x(L)(N)-Bcl-2 chimaeric
      protein (containing the N-terminal region of Bcl-x(L)) failed to prevent Bad
      phosphorylation in cells and was unable to block the cytosolic distribution of
      this pro-apoptotic protein. Additional experiments with the Bcl-2(N)-Bcl-x(L)
      chimaeric protein (containing the N-terminal region of Bcl-2) indicated that,
      although the N-terminal region of Bcl-2 is necessary, it is not sufficient for
      sequestering Bad in the mitochondrial membranes. These observations suggest that
      growth-factor-mediated phosphorylation of Bad contributes to the cytoprotective
      function of Bcl-x(L) but not Bcl-2.

PMID- 11583581
TI  - Oxidative dimerization in metallothionein is a result of intermolecular
      disulphide bonds between cysteines in the alpha-domain.
AB  - Upon storage under aerobic conditions metallothioneins (MTs) form a new species,
      which is characterized by a molecular mass approximately twice the size of
      monomeric MT and shifted (113/111)Cd- and (1)H-NMR resonances. The investigation
      of this oxidative dimerization process by NMR spectroscopy allowed us to
      structurally characterize this MT species that has been described to occur in
      vivo and might be synthesized under conditions of oxidative stress. The oxidative
      dimer was characterized by the formation of an intermolecular cysteine disulphide
      bond involving the alpha-domain, and a detailed analysis of chemical shift
      changes and intermolecular nuclear Overhauser effects points towards a disulphide
      bond involving Cys(36). In contrast to the metal-bridged (non-oxidative)
      dimerization, the metal-cysteine cluster structures in both MT domains remain
      intact and no conformational exchange or metal-metal exchange was observed. Also
      in contrast to the many recently reported oxidative processes which involve the
      beta-domain cysteine groups and result in the increased dynamics of the bound
      metal ions in this N-terminal domain, we found no evidence for any increased
      dynamics in the alpha-domain metals following this oxidation. Therefore these
      findings provide additional corroboration that metal binding in the C-terminal
      alpha-domain is rather tight, even under conditions of a changing cellular
      oxidation potential, compared with the more labile/dynamic nature of the metals
      in the N-terminal beta-domain cluster under similar conditions.

PMID- 11583582
TI  - S-phase-specific expression of the Mad3 gene in proliferating and differentiating
      cells.
AB  - The Myc/Max/Mad transcription factor network plays a central role in the control
      of cellular proliferation, differentiation and apoptosis. In order to elucidate
      the biological function of Mad3, we have analysed the precise temporal patterns
      of Mad3 mRNA expression during the cell cycle and differentiation in cultured
      cells. We show that Mad3 is induced at the G1/S transition in proliferating
      cells; expression persists throughout S-phase, and then declines as cells pass
      through G2 and mitosis. The expression pattern of Mad3 is coincident with that of
      Cdc2 throughout the cell cycle. In contrast, the expression of Mad3 during
      differentiation of cultured mouse erythroleukemia cells shows two transient peaks
      of induction. The first of these occurs at the onset of differentiation, and does
      not correlate with the S-phase of the cell cycle, whereas the second is
      coincident with the S-phase burst that precedes the terminal stages of
      differentiation. Our results therefore suggest that Mad3 serves a cell-cycle
      related function in both proliferating and differentiating cells, and that it may
      also have a distinct role at various stages of differentiation.

PMID- 11583583
TI  - Cloning and expression of a single-chain catalytic antibody that acts as a
      glutathione peroxidase mimic with high catalytic efficiency.
AB  - Glutathione peroxidase (GPX) has a powerful role in scavenging reactive oxygen
      species. In previous papers we have developed a new strategy for generating
      abzymes: the monoclonal antibody with a substrate-binding site is first prepared,
      then a catalytic group is incorporated into the monoclonal antibody's binding
      site by using chemical mutation [Luo, Zhu, Ding, Gao, Sun, Liu, Yang and Shen
      (1994) Biochem. Biophys. Res. Commun. 198, 1240-1247; Ding, Liu, Zhu, Luo, Zhao
      and Ni (1998) Biochem. J. 332, 251-255]. Since then we have established a series
      of catalytic antibodies capable of catalysing the decomposition of hydroperoxides
      by GSH. The monoclonal antibody 2F3 was raised against GSH-S-2,4-dinitrophenyl t
      butyl ester and exhibited high catalytic efficiency, exceeding that of rabbit
      liver GPX, after chemical mutation. To produce pharmaceutical proteins and to
      study the reason why it exhibits high catalytic efficiency, we sequenced, cloned
      and expressed the variable regions of 2F3 antibody as a single-chain Fv fragment
      (2F3-scFv) in different bacterial strains. The amounts of 2F3-scFv proteins
      expressed from JM109 (DE3), BL21 (DE3), and BL21 (coden plus) were 5-10%, 15-20%
      and 25-30% of total bacterial proteins respectively. The 2F3-scFv was expressed
      as inclusion bodies, purified in the presence of 8 M urea by Co(2+)-immobilized
      metal-affinity chromatography (IMAC) and renatured to the active form in vitro by
      gel filtration. The binding constants of the active 2F3-scFv for GSH and GSSG
      were 2.46 x 10(5) M(-1) and 1.03 x 10(5) M(-1) respectively, which were less by
      one order of magnitude than that of the intact 2F3 antibody. The active 2F3-scFv
      was converted into selenium-containing 2F3-scFv (Se-2F3-scFv) by chemical
      modification of the reactive serine; the GPX activity of the Se-2F3-scFv was 3394
      units/micromol, which approaches the activity of rabbit liver GPX.

PMID- 11583585
TI  - Identification of the catalytic nucleophile of the Family 31 alpha-glucosidase
      from Aspergillus niger via trapping of a 5-fluoroglycosyl-enzyme intermediate.
AB  - The mechanism-based reagent 5-fluoro-alpha-d-glucopyranosyl fluoride (5F alpha
      GlcF) was used to trap a glycosyl-enzyme intermediate and identify the catalytic
      nucleophile at the active site of Aspergillus niger alpha-glucosidase (Family
      31). Incubation of the enzyme with 5F alpha GlcF, followed by peptic proteolysis
      and comparative liquid chromatography/MS mapping allowed the isolation of a
      labelled peptide. Fragmentation analysis of this peptide by tandem MS yielded the
      sequence WYDMSE, with the label located on the aspartic acid residue (D).
      Comparison with the known protein sequence identified the labelled amino acid as
      Asp-224 of the P2 subunit.

PMID- 11583584
TI  - Endothelin-1 induces phosphorylation of GATA-4 transcription factor in the HL-1
      atrial-muscle cell line.
AB  - The transcription factor GATA-4 plays a central role in the regulation of cardiac
      muscle gene transcription. The present study demonstrates that endothelin-1 (ET
      1) induces GATA-4 activation and phosphorylation. The treatment of HL-1 adult
      mouse atrial-muscle cells with ET-1 (30 nM) caused a rapid increase in the DNA
      binding activity of GATA-4 within 3 min. The activation was associated with an
      upward mobility shift of the GATA-4 band on native PAGE in an electrophoretic-
      mobility-shift assay. The upward shift of the GATA-4 band also occurred on
      SDS/PAGE as monitored by immunoblotting. The in vitro treatment of nuclear
      extracts with lambda-protein phosphatase abolished the upward shift, indicating
      that GATA-4 was phosphorylated. ET-1 activated the p44/42 mitogen-activated
      protein kinase (MAPK) and the MAPK kinase (MEK) within 3 min, and PD98059 (a
      specific inhibitor of MEK) abolished the ET-1-induced GATA-4 phosphorylation. PMA
      also caused the rapid activation of MAPK and the phosphorylation of GATA-4. In
      contrast, the activation of MAPK by phenylephrine or H(2)O(2) was weak and did
      not lead to GATA-4 phosphorylation. Thus ET-1 induces a GATA-4 phosphorylation by
      activating a MEK-MAPK pathway.

PMID- 11583586
TI  - Cloning and characterization of the mouse polyamine-modulated factor-1 (mPMF-1)
      gene: an alternatively spliced homologue of the human transcription factor.
AB  - The natural polyamines and their analogues have been implicated in
      transcriptional regulation of specific genes. Human polyamine-modulated factor-1
      (hPMF-1) was the first polyamine-responsive transcription factor identified. Here
      the mouse homologue of the hPMF-1 gene is described. Interestingly, the mouse
      gene (mPMF-1) codes for two alternatively spliced mRNAs. Both of the mouse splice
      variants, mPMF-1S and mPMF-1L, possess C-terminal coiled-coil domains nearly
      identical to that found in hPMF-1 and are highly homologous with the human
      protein. The C-terminal coiled-coil structure is necessary for transcriptional
      activation. However, the shorter protein, mPMF-1S, does not contain an N-terminal
      coiled-coil region as do both hPMF-1 and the longer mPMF-1L. mPMF-1L mRNA codes
      for a protein of 202 amino acids, 37 amino acids longer than the human protein.
      By contrast, mPMF-1S codes for only 133 amino acids, as a result of two exons
      being omitted compared with mPMF-1L. Both mouse transcription factors can
      interact with Nrf-2 (nuclear factor-E2-related factor 2), the normal partner of
      hPMF-1, substantiating the importance of the C-terminal coiled-coil region
      responsible for this interaction. Finally, the expression of mPMF-1 is induced
      when mouse M1 myeloid leukaemia cells are exposed to polyamine analogues,
      suggesting control similar to that observed for the hPMF-1.

PMID- 11583587
TI  - Identification of a novel integral plasma membrane protein induced during
      adipocyte differentiation.
AB  - Adipocyte differentiation is co-ordinately regulated by several transcription
      factors and is accompanied by changes in the expression of a variety of genes.
      Using mRNA differential display analysis, we have isolated a novel mRNA, DD16,
      specifically induced during the course of adipocyte differentiation. DD16 mRNAs
      are present in several tissues, but among the tissues tested, a remarkably higher
      level of expression was found in white adipose tissue. The DD16 cDNA encoded a
      polypeptide of 415 amino acids containing a single N-glycosylation site and an N
      terminal hydrophobic stretch of 19 amino acids forming a transmembrane segment,
      indicating that DD16 is a glycosylated membrane-bound protein. Polyclonal
      antibodies raised against the DD16 peptide detected immunoreactive DD16 in
      membrane fractions, notably the plasma membrane. Association of DD16 with the
      plasma membrane was further confirmed by biotinylation studies of cell surface
      proteins, suggesting that DD16 is an integral plasma membrane protein. Therefore
      we propose to give DD16 the name APMAP (Adipocyte Plasma Membrane-Associated
      Protein). Although the biological function of this polypeptide is presently
      unknown, our data suggest that APMAP may function as a novel protein involved in
      the cross-talk of mature adipocytes with the environment.

PMID- 11583589
TI  - The result of equilibrium-constant calculations strongly depends on the
      evaluation method used and on the type of experimental errors.
AB  - The determination of equilibrium constants is a widespread tool both to
      understand and to characterize protein-protein interactions. A variety of
      different methods, among them Scatchard analysis, is used to calculate these
      constants. Although more than 1000 articles dealing with equilibrium constants
      are published every year, the effects of experimental errors on the results are
      often disregarded when interpreting the data. In the present study we
      theoretically analysed the effect of various types of experimental errors on
      equilibrium constants derived by three different methods. A computer simulation
      clearly showed that certain experimental errors, namely inaccurate background
      correction, inexact calibration, saturation effects, slow kinetics and simple
      scattering, can adversely affect the result. The analysis further revealed that,
      for a given type of error, the same data set can produce different results
      depending on the method used.

PMID- 11583588
TI  - Functional analysis of the interleukin-1-receptor-associated kinase (IRAK-1) in
      interleukin-1 beta-stimulated nuclear factor kappa B (NF-kappa B) pathway
      activation: IRAK-1 associates with the NF-kappa B essential modulator (NEMO) upon
      receptor stimulation.
AB  - The interleukin-1 (IL-1)-receptor-associated kinase (IRAK-1) is essential for IL
      1-stimulated nuclear factor kappa B (NF-kappa B) activation. To study the role of
      IRAK-1 in IL-1 beta signalling, we have generated a set of IRAK-1 variants that
      express distinct domains of IRAK-1 either alone or in combination and have
      examined their effects on an NF-kappa B-responsive reporter in HeLa cells. Unlike
      full-length IRAK-1, the deletion mutants were unable to activate NF-kappa B in
      the absence of cytokine stimulation. However, an IRAK-1 variant lacking only the
      N-terminal domain retained the ability of the full-length protein to potentiate
      both IL-1 beta and tumour necrosis factor alpha (TNF alpha)-induced NF-kappa B
      activation. In contrast, expression of the N-terminus or the C-terminus of IRAK
      1, or a fusion protein incorporating both domains, inhibited both IL-1 beta- and
      TNF alpha-induced effects. Expression of an IRAK-1 variant lacking only the C
      terminal domain preferentially inhibited IL-1 beta versus TNF alpha-induced NF
      kappa B activation. These data suggest that the C-terminal domain may link IRAK-1
      to downstream signalling components common to both the IL-1 and TNF pathways.
      Furthermore, we have demonstrated that endogenous IRAK-1 becomes phosphorylated
      upon IL-1 beta treatment and can be detected along with NF-kappa B essential
      modulator (NEMO) and I kappa B kinase beta (IKK beta) in high-molecular-mass
      complexes of 600-800 kDa. Moreover, IRAK-1 could be detected in NEMO
      immunoprecipitates from IL-1 beta-stimulated cells. We conclude that IRAK-1
      mediates IL-1 beta signal transduction through a ligand-dependent association of
      IRAK-1 with the IKK complex.

PMID- 11583590
TI  - Different combinations of the heat-shock cognate protein 70 (hsc70) C-terminal
      functional groups are utilized to interact with distinct tetratricopeptide repeat
      containing proteins.
AB  - A group of tetratricopeptide repeat (TPR)-containing proteins has been shown to
      interact with the C-terminal domain of the 70 kDa heat-shock cognate protein
      (hsc70). In the present study, the effect of the TPR-containing proteins,
      including the C-terminus of hsc70-interacting protein (CHIP), TPR1 and human
      glutamine-rich TPR-containing protein (hSGT), on refolding of luciferase by DnaJ
      and hsc70 was investigated. These proteins inhibited the restoration of
      luciferase activity by the chaperones. The inhibitory effect exerted by TPR1 and
      hSGT depended upon their binding to hsc70. However, the interaction with hsc70
      did not appear to be required for the inhibition of luciferase refolding by CHIP.
      We also demonstrate that the peptide, GPTIEEVD, corresponding to the C-terminal
      end of hsc70, abolished the association of [(3)H]hsc70 with CHIP, TPR1 and hSGT.
      This implied that the GPTIEEVD motif of hsc70 was responsible for interacting
      with these TPR-containing proteins. However, the GGXP-repeats (where X is any
      aliphatic residue), another C-terminal conserved motif of vertebrate hsc70s, were
      not essential for interacting with the TPR-containing proteins. On the basis of
      mutagenesis studies, it was clear that a unique combination of the functional
      groups in the GPTIEEVD motif were utilized to interact with each TPR-containing
      protein, suggesting that inhibitors can be designed and used to elucidate the
      functional role of these interactions.

PMID- 11583592
TI  - Functional properties of Drosophila inositol trisphosphate receptors.
AB  - The functional properties of the only inositol trisphosphate (IP(3)) receptor
      subtype expressed in Drosophila were examined in permeabilized S2 cells. The
      IP(3) receptors of S2 cells bound (1,4,5)IP(3) with high affinity (K(d)=8.5+/-1.1
      nM), mediated positively co-operative Ca(2+) release from a thapsigargin
      sensitive Ca(2+) store (EC(50)=75+/-4 nM, Hill coefficient=2.1+/-0.2), and they
      were recognized by an antiserum to a peptide conserved in all IP(3) receptor
      subtypes in the same way as mammalian IP(3) receptors. As with mammalian IP(3)
      receptors, (2,4,5)IP(3) (EC(50)=2.3+/-0.3 microM) and (4,5)IP(2) (EC(50) approx.
      10 microM) were approx. 20- and 100-fold less potent than (1,4,5)IP(3).
      Adenophostin A, which is typically approx. 10-fold more potent than IP(3) at
      mammalian IP(3) receptors, was 46-fold more potent than IP(3) in S2 cells
      (EC(50)=1.67+/-0.07 nM). Responses to submaximal concentrations of IP(3) were
      quantal and IP(3)-evoked Ca(2+) release was biphasically regulated by cytosolic
      Ca(2+). Using rapid superfusion to examine the kinetics of IP(3)-evoked Ca(2+)
      release from S2 cells, we established that IP(3) (10 microM) maximally activated
      Drosophila IP(3) receptors within 400 ms. The activity of the receptors then
      slowly decayed (t(1/2)=2.03+/-0.07 s) to a stable state which had 47+/-1% of the
      activity of the maximally active state. We conclude that the single subtype of
      IP(3) receptor expressed in Drosophila has similar functional properties to
      mammalian IP(3) receptors and that analyses of IP(3) receptor function in this
      genetically tractable organism are therefore likely to contribute to
      understanding the roles of mammalian IP(3) receptors.

PMID- 11583591
TI  - Study of the interaction of the medium chain mu 2 subunit of the clathrin
      associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and
      CD28.
AB  - The medium chain mu 2 subunit (AP50) of the clathrin-associated adapter protein
      complex 2 (AP-2) interacts specifically with the tyrosine-based signals of
      several integral membrane proteins through the consensus sequence YXXPhi, where X
      can be any residue and Phi is a large hydrophobic residue. Using surface plasmon
      resonance combined with structural information, we have analysed the interaction
      of AP50 with peptides derived from the cytoplasmic tail of cytotoxic T-lymphocyte
      antigen 4 (CTLA-4). The crystal structure of AP50 in complex with a CTLA-4
      derived peptide was determined to 3.6 A (1 A=0.1 nm) resolution. The binding
      domain of AP50 (residues 164-435) was expressed in Escherichia coli and purified.
      In agreement with previous reports, the AP50 domain bound to residues 152-174 of
      CTLA-4, but not to the same peptide that was phosphorylated at the single
      tyrosine residue (position 165). The interaction exhibited fast kinetics with
      rapid on and off rates and a K(d) of 0.7 microM. In order to further understand
      why AP50 binds to CTLA-4, but not to the homologous receptor CD28, a comparison
      of binding of AP50 with five peptides with single changes in and around the
      YXXPhi motif to the equivalent residues of CD28 was made. T162H greatly reduced
      binding, whereas T161L had little effect. Mutations G163S, V164D and K167N all
      exhibited reduced binding. Modelling of the single amino acid changes using
      structural information, was in broad agreement with the binding data,
      demonstrating that residues outside of the YXXPhi motif are also important in the
      interaction of membrane proteins with AP50.

PMID- 11583593
TI  - Characterization of human glucose transporter (GLUT) 11 (encoded by SLC2A11), a
      novel sugar-transport facilitator specifically expressed in heart and skeletal
      muscle.
AB  - Human GLUT11 (encoded by the solute carrier 2A11 gene, SLC2A11) is a novel sugar
      transporter which exhibits significant sequence similarity with the members of
      the GLUT family. The amino acid sequence deduced from its cDNAs predicts 12
      putative membrane-spanning helices and all the motifs (sugar-transporter
      signatures) that have previously been shown to be essential for sugar-transport
      activity. The closest relative of GLUT11 is the fructose transporter GLUT5
      (sharing 41.7% amino acid identity with GLUT11). The human GLUT11 gene (SLC2A11)
      consists of 12 exons and is located on chromosome 22q11.2. In human tissues, a
      7.2 kb transcript of GLUT11 was detected exclusively in heart and skeletal
      muscle. Transfection of COS-7 cells with GLUT11 cDNA significantly increased the
      glucose-transport activity reconstituted from membrane extracts as well as the
      specific binding of the sugar-transporter ligand cytochalasin B. In contrast to
      that of GLUT4, the glucose-transport activity of GLUT11 was markedly inhibited by
      fructose. It is concluded that GLUT11 is a novel, muscle-specific transport
      facilitator that is a member of the extended GLUT family of sugar/polyol
      transport facilitators.

PMID- 11583594
TI  - Pharmacological characterization of the putative cADP-ribose receptor.
AB  - cADP-ribose (cADPR), a naturally occurring metabolite of NAD(+), has been shown
      to be an important regulator of intracellular Ca(2+) release. Considerable
      evidence suggests that cADPR is the endogenous modulator of the ryanodine
      receptor (RyR), which mediates Ca(2+)-induced Ca(2+) release (CICR). Indeed,
      cADPR-mediated Ca(2+) release is subject to functional regulation by other
      modulators of CICR, including Ca(2+), caffeine and calmodulin. However, the
      underlying basis behind the effect of such agents on cADPR activity (in
      particular whether they regulate cADPR binding), as well as the precise nature of
      the cADPR receptor remains unclear. In the present study, use of (32)P
      radiolabelled cADPR has enabled a detailed pharmacological characterization of
      cADPR-binding sites in sea urchin egg homogenates. We report that cADPR binds
      specifically to a single class of high affinity receptor. Retainment of binding
      to membranes after a high-salt wash suggests the involvement of either an
      integral membrane protein (possibly the RyR itself) or a peripheral protein
      tightly associated to the membrane. Insensitivity of [(32)P]cADPR binding to
      either FK506 or rapamycin suggests that this does not concern the FK506-binding
      protein. Significantly, binding is highly robust, being relatively insensitive to
      both endogenous and pharmacological modulators of RyR-mediated CICR. In turn,
      this suggests that such agents modulate cADPR-mediated Ca(2+) release primarily
      by tuning the 'gain' of the CICR system, upon which cADPR acts, rather than
      influencing the interaction of cADPR with its target receptor. The exception to
      this is calmodulin, for which our results indicate an additional role in
      facilitating cADPR binding.

PMID- 11583596
TI  - A contribution towards simplifying area-wide tsetse surveys using medium
      resolution meteorological satellite data.
AB  - A raster or grid-based Geographic Information System with data on tsetse,
      trypanosomiasis, animal production, agriculture and land use has recently been
      developed in Togo. The area-wide sampling of tsetse fly, aided by satellite
      imagery, is the subject of two separate papers. This paper follows on a first
      paper, published in this journal, describing the generation of digital tsetse
      distribution and abundance maps and how these accord with the local climatic and
      agro-ecological setting. Such maps when combined with data on the disease, the
      hosts and their owners, should contribute to the knowledge of the spatial
      epidemiology of trypanosomiasis and assist planning of integrated control
      operations. Here we address the problem of generating tsetse distribution and
      abundance maps from remotely sensed data, using a restricted amount of field
      data. Different discriminant analysis models have been applied using contemporary
      tsetse data and remotely sensed, low resolution data acquired from the National
      Oceanographic and Atmospheric Administration (NOAA) and Meteosat platforms. The
      results confirm the potential of satellite data application and multivariate
      analysis for the prediction of the tsetse distribution and abundance. This opens
      up new avenues because satellite predictions and field data may be combined to
      strengthen and/or substitute one another. The analysis shows how the strategic
      incorporation of satellite imagery may minimize field collection of data. Field
      surveys may be modified and conducted in two stages, first concentrating on the
      expected fly distribution limits and thereafter on fly abundance. The study also
      shows that when applying satellite data, care should be taken in selecting the
      optimal number of predictor variables because this number varies with the amount
      of training data for predicting abundance and on the homogeneity of the
      distribution limits for predicting fly presence. Finally, it is suggested that in
      addition to the use of contemporary training data and predictor variables,
      training and predicted data sets should refer to the same eco-geographic zone.

PMID- 11583595
TI  - Critical roles for the serine 20, but not the serine 15, phosphorylation site and
      for the polyproline domain in regulating p53 turnover.
AB  - The p53 tumour suppressor protein is a short-lived transcription factor that
      becomes stabilized in response to a wide range of cellular stresses.
      Ubiquitination and the targeting of p53 for degradation by the proteasome are
      mediated by Mdm2 (mouse double minute clone 2), a negative regulatory partner of
      p53. Previous studies have suggested that DNA-damage-induced phosphorylation of
      p53 at key N-terminal sites has a pivotal role in regulating the interaction with
      Mdm2 but the precise role of phosphorylation of serines 15 and 20 is still
      unclear. Here we show that replacement of serine 15 and a range of other key N
      terminal phosphorylation sites with alanine, which cannot be phosphorylated, has
      little effect on the ubiquitination and degradation of full-length human p53. In
      contrast, replacement of serine 20 makes p53 highly sensitive to Mdm2-mediated
      turnover. These results define distinct roles for serines 15 and 20, two sites
      previously demonstrated to be dependent on phosphorylation through mechanisms
      mediated by DNA damage and ATM (ataxia telangiectasia mutated). We also show that
      the polyproline region of p53, a domain that has a key role in p53-induced
      apoptosis, exerts a critical influence over the Mdm2-mediated turnover of p53.

PMID- 11583597
TI  - Comparative development, longevity and population growth of exotic and native
      parasitoids of lepidopteran cereal stemborers in Kenya.
AB  - Studies on the effect of temperature on the development, longevity and population
      growth of Cotesia flavipes Cameron and Cotesia sesamiae (Cameron) indicated that
      the development of both Cotesia spp. from oviposition to cocoon formation and
      adult emergence was inversely related to temperature. The longevity of the
      parasitoids was also inversely related to temperature. Both parasitoids lived
      longer when moisture and food (agar + honey/water) were provided. The mean number
      of females and total adult progeny produced by C. flavipes on two host species
      were, in most cases, higher than C. sesamiae. The intrinsic rate of natural
      increase of C. flavipes was higher than that of C. sesamiae.

PMID- 11583598
TI  - Larval diet affects number of femoral 'brush' scales in male Helicoverpa
      punctigera moths (Lepidoptera: Noctuidae).
AB  - Males of Helicoverpa punctigera (Wallengren) show considerable variation in the
      number of femoral scales on the prothoracic legs. Such intraspecific variation in
      adult morphology could indicate the presence of undetected sibling species, or it
      may be related to larval diet. Helicoverpa punctigera is polyphagous, and
      different host plant species are likely to represent diets of different quality.
      Femoral lengths and the numbers of femoral scales on the prothoracic legs were
      therefore determined from: (i) individuals that had been collected as larvae from
      various host species in the field; and (ii) individuals that had been laboratory
      reared, in split-family tests, on different diets, namely cotton, lucerne,
      sowthistle and artificial diet. Host plant species (and therefore presumably diet
      quality) influenced femoral length of H. punctigera males and, perhaps in
      conjunction with this, the number of femoral scales on the fore leg. The rearing
      experiment indicated, in addition, that the effect of host plant quality varies
      with larval stage, and that the pattern of this variation across the immature
      stages is dependent on host plant species. The recorded variation in the
      morphology of field-collected H. punctigera males is therefore most readily
      explained as a consequence of different individuals developing (at least for most
      of their larval life) on different host plant species, with diet quality varying
      significantly with species. The relevance of these results for insect
      developmental studies and evolutionary interpretations of host relationships is
      outlined.

PMID- 11583599
TI  - Body size as an indicator of parasitoid quality in male and female Anagyrus
      kamali (Hymenoptera: Encyrtidae).
AB  - The parasitoid Anagyrus kamali Moursi was recently introduced into the Caribbean
      as a biological control agent against the hibiscus mealybug, Maconellicoccus
      hirsutus Green. In the laboratory, parasitoid size, as measured by left hind
      tibia length, was positively correlated with several indicators of the
      parasitoid's fitness: longevity, mating preference, fecundity, reproductive
      longevity, progeny emergence and sex-ratio. When fed ad libidum with honey drops,
      large male parasitoids lived significantly longer (29.1 +/- 6.5 days) than small
      ones (18.4 +/- 5.7 days). Large females also lived significantly longer (35.4 +/-
      10 days) than small females (27.9 +/- 9.6 days). Females showed no significant
      mating preference between large and small males. Lifetime fecundity was
      positively correlated with the size of adult females and ranged from 37 +/- 21
      eggs for small females to 96 +/- 43 eggs for large ones. The reproductive
      longevity, daily oviposition rate, and number of progeny were also higher among
      large parasitoids. The sex ratio of progeny from small female parasitoids was
      higher (0.76 +/- 0.24) than that of large individuals (0.47 +/- 0.18).

PMID- 11583600
TI  - Encarsia species (Hymenoptera: Aphelinidae) of Australia and the Pacific Islands
      attacking Bemisia tabaci and Trialeurodes vaporariorum (Hemiptera: Aleyrodidae)-
      a pictorial key and descriptions of four new species.
AB  - After the recent introduction of the pest whitefly Bemisia tabaci (Gennadius)
      biotype B into Australia, research was undertaken to study the parasitoids of the
      long established native B. tabaci and Trialeurodes vaporariorum (Westwood). The
      genus Encarsia contains species which are important biological control agents of
      whiteflies and hard scales. The taxonomy of the Encarsia species attacking B.
      tabaci and T. vaporariorum in Australia and the Pacific Islands is revised. DNA
      sequencing of the 28S D2 ribosomal DNA was used to characterize species. Sixteen
      species are recognized, with 12 occurring in Australia, eight in the Pacific
      region, and four in both regions. All except one species (E. formosa Gahan) are
      new records for Australia. Four species are described as new from Australia: E.
      accenta Schmidt & Naumann sp. n., E. adusta Schmidt & Naumann sp. n., E.
      oakeyensis Schmidt & Naumann sp. n., and E. ustulata Schmidt & Naumann sp. n.
      Diagnostic descriptions are given for all species and each species is
      illustrated. A pictorial key is provided to allow the identification of species
      by non-specialists.

PMID- 11583601
TI  - Descriptions of the Anopheles (Cellia) farauti complex of sibling species
      (Diptera: Culicidae) in Australia.
AB  - Descriptions of the three sibling species of the Anopheles farauti complex in
      Australia, A. farauti Laveran (formerly A. farauti No. 1), A. hinesorum Schmidt
      sp.n. (formerly A. farauti No. 2) and A. torresiensis Schmidt sp.n. (formerly A.
      farauti No. 3) are provided. These species form a part of the punctulatus group,
      which contains the major malaria vectors in the southwest Pacific. Morphological
      markers are described for adult females, fourth instar larvae and pupae which
      identify most specimens, and are presented in keys.

PMID- 11583602
TI  - Oviposition behaviour and host colony size discrimination in Episyrphus balteatus
      (Diptera: Syrphidae).
AB  - Three bioassays were used to examine the oviposition behaviour of the hoverfly,
      Episyrphus balteatus (Degeer) in which various stimuli purported to influence
      host assessment and choice were tested. Episyrphus balteatus failed to exhibit
      enhanced behavioural responses, in terms of approaches and landings, to
      artificial leaves with the highest numbers of aphids, suggesting that females are
      merely responding to the colour of the artificial leaves. A density-dependent
      oviposition response was reported in a second bioassay using whole bean plants,
      although there was an asymptotic relationship. Syrphid responses, which were
      measured by oviposition over a five-day period, were greatest towards those
      plants with the highest number of aphids. In a final series of trials, gravid
      female E. balteatus showed a behavioural preference for filter papers treated
      with the greatest honeydew concentrations (0.26 mg microl(-1) honeydew). More
      time was spent in the treated areas and syrphids demonstrated more proboscis and
      ovipositor extensions in these treatments. These bioassays provided an
      opportunity to isolate some of the individual components of decision-making by
      female E. balteatus during egg-laying behaviour. A greater understanding of
      natural enemy behaviour is essential before enhanced control of pest populations
      in the field can be established.

PMID- 11583603
TI  - No man is an island.

PMID- 11583604
TI  - Evidence-based dentistry: Part V. Critical appraisal of the dental literature:
      papers about therapy.
AB  - Evidence-based dentistry involves defining a question focused on a patient
      related problem and searching for reliable evidence to provide an answer. Once
      potential evidence has been found, it is necessary to determine whether the
      information is credible and whether it is useful in your practice by using the
      techniques of critical appraisal. In this paper, the fifth in a 6-part series on
      evidence-based dentistry, a framework is described which provides a series of
      questions to help the reader assess both the validity and applicability of an
      article related to questions of therapy or prevention.

PMID- 11583605
TI  - Clinical practice guidelines in dentistry: Part II. By dentists, for dentists.
AB  - There is a growing interest in clinical practice guidelines (CPGs) for all health
      care providers. As discussed in the first paper of this 2-part series, there are
      many misperceptions about guidelines and their potential risks and benefits. The
      dental profession in Canada, cognizant of both the importance and the challenges
      of developing sound, credible and relevant guidelines for dentists, has created a
      unique, autonomous collaboration of multiple stakeholders, the Canadian
      Collaboration on CPGs in Dentistry (CCCD). This paper discusses the history,
      structure and processes of the CCCD and introduces the first guideline under
      development by and for Canadian dentists.

PMID- 11583606
TI  - Diagnosis of occlusal caries: Part I. Conventional methods.
AB  - Accurate diagnosis of the presence or absence of disease is a fundamental
      requirement in health care. The diagnosis of non-overt occlusal decay is
      challenging and can be highly subjective, and its inherent uncertainties can lead
      to widely differing treatment decisions. The development of more sensitive,
      specific and reproducible diagnostic tools for occlusal surfaces would contribute
      greatly to more precise planning of preventive and operative therapy. The purpose
      of this 2-part paper is to review current knowledge concerning conventional and
      new diagnostic methods for occlusal caries. Part I looks at established
      diagnostic methods for occlusal surfaces. Conventional visual, tactile and
      radiographic examinations provide less-than-ideal diagnostic sensitivity. Neither
      fissure discolouration (black or brown) nor the use of an explorer has been shown
      to improve diagnostic accuracy. However, the combination of careful visual
      examination with optimal radiographic examination affords better diagnostic
      performance. The best visual indicators involve precise features associated with
      the presence of disease, such as opaque fissure demineralization and the presence
      and extent of localized breakdown of the enamel. For best results, teeth should
      be clean, thoroughly dry and well illuminated. Part II will examine new and
      emerging technologies, including the DIAGNOdent laser fluorescence device, which
      are being developed for the diagnosis of occlusal decay.

PMID- 11583607
TI  - Diagnosis of occlusal caries: Part II. Recent diagnostic technologies.
AB  - Accurate diagnosis of the presence or absence of disease is a fundamental
      requirement in health care. The diagnosis of non-overt occlusal decay is
      challenging and can be highly subjective, and its inherent uncertainties can lead
      to widely differing treatment decisions. The purpose of this 2-part paper is to
      review current knowledge concerning conventional and new diagnostic methods for
      occlusal caries. Part I looked at established methods for diagnosing occlusal
      decay. These methods have several limitations, particularly in their ability to
      diagnose early carious lesions. Part II examines new and emerging technologies
      that are being developed for the diagnosis of occlusal decay. Electrical
      conductance measurements and quantitative laser- or light-induced fluorescence
      represent significant improvements over conventional diagnostic methods,
      especially for in vitro applications and particularly with regard to sensitivity
      and reproducibility. Proponents of the DIAGNOdent laser fluorescence system claim
      that it evaluates the fluorescence that develops when laser light is incident on
      areas of demineralization. This noninvasive device is simple to use and provides
      quantitative data. Studies supporting its validity are limited but do suggest
      good sensitivity and excellent reproducibility. However, the DIAGNOdent system
      requires more scientific scrutiny. Although it offers a high rate of disease
      detection, it has little ability to indicate the extent of decay. In all
      treatment decisions, clinicians must be aware of the limitations of the
      diagnostic methods that have been used. Clinical judgment based on the patient s
      case history, visual cues, review of radiographs and probability of disease is
      still the most important aspect of optimum patient care. New technologies may
      provide supplemental information, but they cannot yet replace established methods
      for the diagnosis of occlusal caries.

PMID- 11583608
TI  - Theme and variations: juxtamembrane regulation of receptor protein kinases.
AB  - Huse et al. in this issue of Molecular Cell and Wybenga-Groot et al. in the
      September 21, 2001 issue of Cell present biochemical and structural studies that
      elucidate the roles of juxtamembrane phosphorylation in a receptor
      serine/threonine kinase, the type I receptor for transforming growth factor beta,
      and in a receptor tyrosine kinase, the ephrin receptor EphB2.

PMID- 11583609
TI  - Death signals changes in TFIID.
AB  - In this issue of Molecular Cell, Bell et al. identify an isoform of hTAF(II)80
      that is induced in response to several proapoptotic stimuli. The finding that
      extracellular signals can lead to changes in the subunit composition of TFIID
      provides an example of how regulated activity of the general transcription
      factors may contribute to inducible programs of gene expression.

PMID- 11583610
TI  - Protein transport: two translocons are better than one.
AB  - The translocon is the gateway to the endoplasmic reticulum (ER). In yeast this is
      the Sec61p complex. However, new evidence suggests that a second translocon
      containing the Sec61p homolog Ssh1p provides important flexibility to the ER
      translocation machinery.

PMID- 11583611
TI  - To cleave or not to cleave? Insights from the LexA crystal structure.
AB  - In the September 7, 2001 issue of Cell, Luo et al. describe the structure of LexA
      protein in two states, cleavable and noncleavable. This structure offers new
      insights into how LexA and other structurally related proteins, such as lambda
      and UmuD, undergo autocatalytic cleavage using a Ser-Lys dyad.

PMID- 11583612
TI  - Common themes in mechanisms of gene silencing.
AB  - The assembly of DNA into regions of inaccessible chromatin, called silent
      chromatin, is involved in the regulation of gene expression and maintenance of
      chromosome stability in eukaryotes. Recent studies on Sir2-containing silencing
      complexes in budding yeast and HP1- and Swi6-containing silencing complexes in
      metazoans and fission yeast suggest a common mechanism for the assembly of these
      domains, which involves the physical coupling of histone modifying enzymes to
      histone binding proteins.

PMID- 11583613
TI  - Ubiquitin enters the new millennium.
AB  - The latest advances in ubiquitin-mediated signaling were discussed at a recent
      FASEB meeting in Vermont. New findings show that besides signaling proteolysis,
      ubiquitination can be a signal for trafficking, kinase activation, and other
      nonproteolytic fates.

PMID- 11583614
TI  - Composition and functional characterization of yeast 66S ribosome assembly
      intermediates.
AB  - The pathway and complete collection of factors that orchestrate ribosome assembly
      are not clear. To address these problems, we affinity purified yeast preribosomal
      particles containing the nucleolar protein Nop7p and developed means to separate
      their components. Nop7p is associated primarily with 66S preribosomes containing
      either 27SB or 25.5S plus 7S pre-rRNAs. Copurifying proteins identified by mass
      spectrometry include ribosomal proteins, nonribosomal proteins previously
      implicated in 60S ribosome biogenesis, and proteins not known to be involved in
      ribosome production. Analysis of strains mutant for eight of these proteins not
      previously implicated in ribosome biogenesis showed that they do participate in
      this pathway. These results demonstrate that proteomic approaches in concert with
      genetic tools provide powerful means to purify and characterize ribosome assembly
      intermediates.

PMID- 11583615
TI  - Identification of a 60S preribosomal particle that is closely linked to nuclear
      export.
AB  - A nuclear GTPase, Nug1p, was identified in a genetic screen for components linked
      to 60S ribosomal subunit export. Nug1p cosedimented with nuclear 60S preribosomes
      and was required for subunit export to the cytoplasm. Tagged Nug1p coprecipitated
      with proteins of the 60S subunit, late precursors to the 25S and 5.8S rRNAs, and
      at least 21 nonribosomal proteins. These included a homologous nuclear GTPase,
      Nug2p, the Noc2p/Noc3p heterodimer, Rix1p, and Rlp7p, each of which was
      implicated in 60S subunit export. Other known ribosome synthesis factors and
      proteins of previously unknown function, including the 559 kDa protein Ylr106p,
      also copurified. Eight of these proteins were copurified with nuclear pore
      complexes, suggesting that this complex represents the transport intermediate for
      60S subunit export.

PMID- 11583616
TI  - Dual functions of largest NURF subunit NURF301 in nucleosome sliding and
      transcription factor interactions.
AB  - NURF is an ISWI complex of four proteins that uses the energy of ATP hydrolysis
      to catalyze nucleosome sliding. Three NURF components have been identified
      previously. We have cloned cDNA encoding the largest NURF subunit, revealing a
      301 kDa polypeptide (NURF301) that shares structural motifs with ACF1. We have
      reconstituted full and partial NURF complexes from recombinant proteins and show
      that NURF301 and the ISWI ATPase are necessary and sufficient for accurate and
      efficient nucleosome sliding. An HMGA/HMGI(Y)-like domain of NURF301 that
      facilitates nucleosome sliding indicates the importance of DNA conformational
      changes in the sliding mechanism. NURF301 also shows interactions with sequence
      specific transcription factors, providing a basis for targeted recruitment of the
      NURF complex to specific genes.

PMID- 11583617
TI  - Reconstitution of a functional core polycomb repressive complex.
AB  - The opposing actions of polycomb (PcG) and trithorax group (trxG) gene products
      maintain essential gene expression patterns during Drosophila development. PcG
      proteins are thought to establish repressive chromatin structures, but the
      mechanisms by which this occurs are not known. Polycomb repressive complex 1
      (PRC1) contains several PcG proteins and inhibits chromatin remodeling by trxG
      related SWI/SNF complexes. We have defined a functional core of PRC1 by
      reconstituting a stable complex using four recombinant PcG proteins. One subunit,
      PSC, can also inhibit chromatin remodeling on its own. These PcG proteins create
      a chromatin structure that has normal nucleosome organization and is accessible
      to nucleases but excludes hSWI/SNF.

PMID- 11583618
TI  - Linking the Rb and polycomb pathways.
AB  - Polycomb group (PcG) proteins associate to form complexes that repress Hox genes,
      thereby imposing the patterning of Hox expression required for development.
      However, these proteins have a second Hox-independent role in regulating cell
      proliferation. Our results suggest that association between Rb and PcG proteins
      forms a repressor complex that blocks entry of cells into mitosis. Also, we
      provide evidence that Rb colocalizes with nuclear PcG complexes and is important
      for association of PcG complexes with nuclear targets. The Rb-PcG complex may
      provide a means to link cell cycle arrest to differentiation events leading to
      embryonic pattern formation.

PMID- 11583619
TI  - Differential dimer activities of the transcription factor Oct-1 by DNA-induced
      interface swapping.
AB  - Two crystal structures of Oct-1 POU domain bound to DNA provide a rationale for
      differential, conformation-dependent recruitment of transcription cofactors. The
      POU-homeo and POU-specific subdomains of Oct-1 contain two different
      nonoverlapping pairs of surface patches that are capable of forming unrelated
      protein-protein interfaces. Members of the POU factor family contain one or two
      conserved sequence motifs in the interface that are known to be phosphorylated,
      as noted for Oct-1 and Pit-1. Modeling of Oct-4 reveals the unique case where the
      same conserved sequence is located in both interfaces. Our studies provide the
      basis for two distinct dimeric POU factor arrangements that are dictated by the
      architecture of each DNA response element. We suggest interface swapping in
      dimers could be a general mechanism of modulating the activity of transcription
      factors.

PMID- 11583620
TI  - A small domain of CBP/p300 binds diverse proteins: solution structure and
      functional studies.
AB  - The transcriptional coactivators CBP and p300 are critical regulators of metazoan
      gene expression. They associate with many different DNA-bound transcription
      factors through small, conserved domains. We have identified a compactly folded
      46 residue domain in CBP and p300, the IRF-3 binding domain (IBiD), and we have
      determined its structure by NMR. It has a helical framework containing an
      apparently flexible polyglutamine loop that participates in ligand binding.
      Spectroscopic data indicate that induced folding accompanies association of IBiD
      with its partners, which exhibit no evident sequence similarities. We demonstrate
      the significance both in vitro and in vivo of interactions between IBiD and a
      number of diverse partners. Thus, IBiD is an important contributor to signal
      integration by CBP and p300.

PMID- 11583621
TI  - Identification of hTAF(II)80 delta links apoptotic signaling pathways to
      transcription factor TFIID function.
AB  - Apoptotic cell death is associated with altered levels of mRNA expression, yet
      the mechanisms that coordinate changes in gene expression with activation of the
      cell death machinery remain obscure. Here, we report the cloning and
      characterization of hTAF(II)80 delta, a specialized isoform of the general
      transcription factor TFIID subunit hTAF(II)80. Several distinct apoptotic stimuli
      induce the expression and caspase-dependent cleavage of hTAF(II)80 delta.
      hTAF(II)80 delta, unlike hTAF(II)80, forms a TFIID-like complex lacking
      hTAF(II)31. Elevated expression of hTAF(II)80 delta in HeLa cells is sufficient
      to trigger apoptotic cell death and selectively alters cellular transcription,
      including the induction of the target genes gadd45 and p21. These data define a
      signaling pathway that couples apoptotic signals to a reprogramming of RNA
      polymerase II transcription.

PMID- 11583622
TI  - Phosphorylation of bid by casein kinases I and II regulates its cleavage by
      caspase 8.
AB  - Bid plays an essential role in Fas-mediated apoptosis of the so-called type II
      cells. In these cells, following cleavage by caspase 8, the C-terminal fragment
      of Bid translocates to mitochondria and triggers the release of apoptogenic
      factors, thereby inducing cell death. Here we report that Bid is phosphorylated
      by casein kinase I (CKI) and casein kinase II (CKII). Inhibition of CKI and CKII
      accelerated Fas-mediated apoptosis and Bid cleavage, whereas hyperactivity of the
      kinases delayed apoptosis. When phosphorylated, Bid was insensitive to caspase 8
      cleavage in vitro. Moreover, a mutant of Bid that cannot be phosphorylated was
      found to be more toxic than wild-type Bid. Together, these data indicate that
      phosphorylation of Bid represents a new mechanism whereby cells control
      apoptosis.

PMID- 11583623
TI  - A serine protease, HtrA2, is released from the mitochondria and interacts with
      XIAP, inducing cell death.
AB  - X chromosome-linked inhibitor of apoptosis (XIAP) is an endogenous inhibitor of
      caspase-3, -7, and -9. Smac/DIABLO, an inhibitor of XIAP, is released from
      mitochondria upon receiving apoptotic stimuli and binds to the BIR2 and BIR3
      domains of XIAP, thereby inhibiting its caspase-inhibitory activity. Here we
      report that a serine protease called HtrA2/Omi is released from mitochondria and
      inhibits the function of XIAP by direct binding in a similar way to Smac.
      Moreover, when overexpressed extramitochondrially, HtrA2 induces atypical cell
      death, which is neither accompanied by a significant increase in caspase activity
      nor inhibited by caspase inhibitors, including XIAP. A catalytically inactive
      mutant of HtrA2, however, does not induce cell death. In short, HtrA2 is a Smac
      like inhibitor of IAP activity with a serine protease-dependent cell death
      inducing activity.

PMID- 11583624
TI  - A model for the gamma delta resolvase synaptic complex.
AB  - The serine recombinase gamma delta resolvase performs site-specific recombination
      in an elaborate synaptic complex containing 12 resolvase subunits and two 114
      base pair res sites. Here we present an alternative structural model for the
      synaptic complex. Resolvase subunits in the complex contact their neighbors in
      equivalent ways, using three principal interactions, one of which is a newly
      proposed synaptic interaction. Evidence in support of this interaction is
      provided by mutations at the interface that either enable resolvase to synapse
      two copies of site I or inhibit synapsis of complete res sites. In our model, the
      two crossover sites are far apart, separated by the resolvase catalytic domains
      bound to them. Thus, recombination would require a substantial rearrangement of
      resolvase subunits or domains.

PMID- 11583625
TI  - The Structure of calnexin, an ER chaperone involved in quality control of protein
      folding.
AB  - The three-dimensional structure of the lumenal domain of the lectin-like
      chaperone calnexin determined to 2.9 A resolution reveals an extended 140 A arm
      inserted into a beta sandwich structure characteristic of legume lectins. The arm
      is composed of tandem repeats of two proline-rich sequence motifs which interact
      with one another in a head-to-tail fashion. Identification of the ligand binding
      site establishes calnexin as a monovalent lectin, providing insight into the
      mechanism by which the calnexin family of chaperones interacts with
      monoglucosylated glycoproteins.

PMID- 11583626
TI  - Structural basis for the recognition of a nucleoporin FG repeat by the NTF2-like
      domain of the TAP/p15 mRNA nuclear export factor.
AB  - TAP-p15 heterodimers have been implicated in the export of mRNAs through nuclear
      pore complexes (NPCs). We report a structural analysis of the interaction domains
      of TAP and p15 in a ternary complex with a Phe-Gly (FG) repeat of an NPC
      component. The TAP-p15 heterodimer is structurally similar to the homodimeric
      transport factor NTF2, but unlike NTF2, it is incompatible with either
      homodimerization or Ran binding. The NTF2-like heterodimer functions as a single
      structural unit in recognizing an FG repeat at a hydrophobic pocket present only
      on TAP and not on p15. This FG binding site interacts synergistically with a
      second site at the C terminus of TAP to mediate mRNA transport through the pore.
      In general, our findings suggest that FG repeats bind with a similar conformation
      to different classes of transport factors.

PMID- 11583627
TI  - Structure and regulation of the CDK5-p25(nck5a) complex.
AB  - CDK5 plays an indispensable role in the central nervous system, and its
      deregulation is involved in neurodegeneration. We report the crystal structure of
      a complex between CDK5 and p25, a fragment of the p35 activator. Despite its
      partial structural similarity with the cyclins, p25 displays an unprecedented
      mechanism for the regulation of a cyclin-dependent kinase. p25 tethers the
      unphosphorylated T loop of CDK5 in the active conformation. Residue Ser159,
      equivalent to Thr160 on CDK2, contributes to the specificity of the CDK5-p35
      interaction. Its substitution with threonine prevents p35 binding, while the
      presence of alanine affects neither binding nor kinase activity. Finally, we
      provide evidence that the CDK5-p25 complex employs a distinct mechanism from the
      phospho-CDK2-cyclin A complex to establish substrate specificity.

PMID- 11583628
TI  - The TGF beta receptor activation process: an inhibitor- to substrate-binding
      switch.
AB  - The type I TGF beta receptor (T beta R-I) is activated by phosphorylation of the
      GS region, a conserved juxtamembrane segment located just N-terminal to the
      kinase domain. We have studied the molecular mechanism of receptor activation
      using a homogeneously tetraphosphorylated form of T beta R-I, prepared using
      protein semisynthesis. Phosphorylation of the GS region dramatically enhances the
      specificity of T beta R-I for the critical C-terminal serines of Smad2. In
      addition, tetraphosphorylated T beta R-I is bound specifically by Smad2 in a
      phosphorylation-dependent manner and is no longer recognized by the inhibitory
      protein FKBP12. Thus, phosphorylation activates T beta R-I by switching the GS
      region from a binding site for an inhibitor into a binding surface for substrate.
      Our observations suggest that phosphoserine/phosphothreonine-dependent
      localization is a key feature of the T beta R-I/Smad activation process.

PMID- 11583629
TI  - Specificity of MAP kinase signaling in yeast differentiation involves transient
      versus sustained MAPK activation.
AB  - Signals transmitted by common components often elicit distinct (yet appropriate)
      outcomes. In yeast, two developmental options-mating and invasive growth-are both
      regulated by the same MAP kinase cascade. Specificity has been thought to result
      from specialized roles for the two MAP kinases, Kss1 and Fus3, and because Fus3
      prevents Kss1 from gaining access to the mating pathway. Kss1 has been thought to
      participate in mating only when Fus3 is absent. Instead, we show that Kss1 is
      rapidly phosphorylated and potently activated by mating pheromone in wild-type
      cells, and that this is required for normal pheromone-induced gene expression.
      Signal identity is apparently maintained because active Fus3 limits the extent of
      Kss1 activation, thereby preventing inappropriate signal crossover.

PMID- 11583630
TI  - Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required
      for endothelial cell chemotaxis.
AB  - The role of the protein kinase Akt in cell migration is incompletely understood.
      Here we show that sphingosine-1-phosphate (S1P)-induced endothelial cell
      migration requires the Akt-mediated phosphorylation of the G protein-coupled
      receptor (GPCR) EDG-1. Activated Akt binds to EDG-1 and phosphorylates the third
      intracellular loop at the T(236) residue. Transactivation of EDG-1 by Akt is not
      required for G(i)-dependent signaling but is indispensable for Rac activation,
      cortical actin assembly, and chemotaxis. Indeed, T236AEDG-1 mutant sequestered
      Akt and acted as a dominant-negative GPCR to inhibit S1P-induced Rac activation,
      chemotaxis, and angiogenesis. Transactivation of GPCRs by Akt may constitute a
      specificity switch to integrate rapid G protein-dependent signals into long-term
      cellular phenomena such as cell migration.

PMID- 11583632
TI  - Involvement of PIAS1 in the sumoylation of tumor suppressor p53.
AB  - Sumoylation of p53 by the ubiquitin-like protein, SUMO-1/sentrin/PIC1, has been
      shown to stimulate its transcriptional activation activity. The SUMO E3 ligase, a
      key enzyme in the recognition of substrates to be sumoylated, has not yet been
      identified. We isolated PIAS1 (protein inhibitor of activated STAT1) as a SUMO-1
      binding protein by yeast two-hybrid screening. In addition, PIAS1 bound p53 and
      Ubc9, the E2 for SUMO. PIAS1 that was mutated in the RING finger-like domain
      bound p53 and SUMO-1, but not Ubc9. PIAS1 catalyzed the sumoylation of p53 both
      in U2OS cells and in vitro in a domain-dependent manner. These data suggest that
      PIAS1 functions as a SUMO ligase, or possibly as a tightly bound regulator of it,
      toward p53.

PMID- 11583631
TI  - BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK
      mediated mitochondrial apoptosis.
AB  - Critical issues in apoptosis include the importance of caspases versus organelle
      dysfunction, dominance of anti- versus proapoptotic BCL-2 members, and whether
      commitment occurs upstream or downstream of mitochondria. Here, we show cells
      deficient for the downstream effectors Apaf-1, Caspase-9, or Caspase-3 display
      only transient protection from "BH3 domain-only" molecules and die a caspase
      independent death by mitochondrial dysfunction. Cells with an upstream defect,
      lacking "multidomain" BAX, BAK demonstrate long-term resistance to all BH3 domain
      only members, including BAD, BIM, and NOXA. Comparison of wild-type versus mutant
      BCL-2, BCL-X(L) indicates these antiapoptotics sequester BH3 domain-only
      molecules in stable mitochondrial complexes, preventing the activation of BAX,
      BAK. Thus, in mammals, BH3 domain-only molecules activate multidomain
      proapoptotic members to trigger a mitochondrial pathway, which both releases
      cytochrome c to activate caspases and initiates caspase-independent mitochondrial
      dysfunction.

PMID- 11583633
TI  - Molecular mechanisms mediating methylation-dependent silencing of ribosomal gene
      transcription.
AB  - Epigenetic control mechanisms silence about half of ribosomal RNA genes (rDNA) in
      metabolically active cells. In the mouse, 40% of rDNA repeats are methylated and
      can be activated by 5-azacytidine treatment. In exploring the effect of
      methylation on rDNA transcription, we found that methylation of a single CpG
      dinucleotide within the upstream control element of the rDNA promoter (at -133)
      abrogates rDNA transcription both in transfection experiments and in in vitro
      assays using chromatin templates. Chromatin immunoprecipitation assays
      demonstrate that methylation of the cytosine at -133 inhibits binding of the
      transcription factor UBF to nucleosomal rDNA, thereby preventing initiation
      complex formation. Thus, methylation may be a mechanism to inactivate rDNA genes
      and propagate transcriptional silencing through cell division.

PMID- 11583635
TI  - Transmyocardial CO(2) laser revascularization improves symptoms, function, and
      quality of life: 12-month results from a randomized controlled trial.
AB  - PURPOSE: To describe differences in health status (symptoms, physical function,
      and quality of life) between continued medical management and transmyocardial
      revascularization with a carbon dioxide laser in patients with severe,
      symptomatic, inoperable coronary artery disease. SUBJECTS AND METHODS: This
      prospective, multicenter trial randomized 98 patients to transmyocardial
      revascularization and 99 to continued medical therapy. Health status was assessed
      with the Seattle Angina Questionnaire and the Short Form-36 at baseline and at 3,
      6, and 12 months. A new analytic technique, the benefit statistic, was developed
      to facilitate interpretability of disease-specific health status assessments over
      time. RESULTS: Of the 99 patients assigned to medical therapy, 59 (60%)
      subsequently underwent transmyocardial revascularization. By an intention-to
      treat analysis, patients initially randomized to transmyocardial
      revascularization had 44% of their angina eliminated versus 21% for the medical
      treatment group (difference = 23%; 95% confidence interval [CI], 11% to 34%).
      Differences in the benefits of transmyocardial revascularization on physical
      limitations (33% vs 11% in the medical arm [difference = 23%; 95% CI, 15% to
      31%]) and quality of life (47% vs 20% in the medical arm [difference = 26%; 95%
      CI, 18% to 35%]) were similarly large. These benefits were apparent at 3 months
      and sustained throughout the 1 year of follow-up. An efficacy analysis that
      excluded patients who crossed over from the medical treatment to transmyocardial
      revascularization arm suggested greater treatment benefits. CONCLUSIONS:
      Transmyocardial revascularization may offer a valuable palliative alternative to
      patients with severe limitations in health status for whom no standard
      revascularization options exist.

PMID- 11583636
TI  - Heart failure in beta thalassemia: a 5-year follow-up study.
AB  - PURPOSE: To evaluate the survival of patients with beta thalassemia and heart
      failure who were treated with iron chelation therapy. SUBJECTS AND METHODS: Fifty
      two consecutive patients with beta thalassemia and heart failure were followed in
      a prospective 5-year study. All patients underwent a full clinical examination
      with chest radiograph, electrocardiogram, and echocardiographic investigation
      performed at 6-month intervals or when a new symptom developed. RESULTS: Of the
      52 patients (mean [+/- SD] age, 24 +/- 5 years), 25 (48%) survived 5 years after
      the onset of heart failure. Forty-three patients had left-sided heart failure,
      and 9 had right-sided heart failure. Those with left-sided heart failure were
      younger at presentation with heart failure (22 +/- 4 years vs. 31 +/- 6 years; P
      <0.001), had lower ejection fractions (36% +/- 9% vs. 64% +/- 10%; P <0.001), and
      had a lower mean serum ferritin level (3355 +/- 1241 ng/mL vs. 6,397 +/- 1,613
      ng/mL; P <0.001). CONCLUSION: The 5-year survival rate in patients with beta
      thalassemia with heart failure was greater than previously reported. There are
      clinical characteristics that may make patients more likely to develop left- or
      right-sided heart failure.

PMID- 11583637
TI  - Exercise-induced myocardial perfusion abnormalities in sickle beta-thalassemia:
      Tc-99m tetrofosmin gated SPECT imaging study.
AB  - PURPOSE: To determine the mechanism of myocardial ischemia in patients with
      sickle beta-thalassemia, we performed a scintigraphic evaluation of myocardial
      perfusion during exercise. SUBJECTS AND METHODS: We studied 30 patients with
      sickle beta-thalassemia, (mean [+/-SD] age, 37 +/- 10 years) who had no
      electrocardiographic (ECG), radiographic, or echo-Doppler signs of pulmonary
      hypertension, left ventricular hypertrophy, or impaired contractility. All
      patients had a hemoglobin level greater than 7 g/dL. Treadmill exercise test was
      performed according to the Bruce protocol. Myocardial perfusion was assessed by
      single-photon emission computed tomography, using Tetrofosmin Tc-99 m Myoview as
      radiotracer, at peak exercise and again 4 hours later. RESULTS: Eight patients
      (27%) developed stress-induced scintigraphic perfusion abnormalities that were
      reversible in all but 1 patient. Subsequent coronary angiograms were normal in
      all 8 patients. ST segment depression was seen during exercise in 5 of the 7
      patients who had reversible perfusion defects. Except for a significantly greater
      white blood cell count, these 5 patients did not differ from the rest of patients
      by sex, age, hemoglobin level, percentage hemoglobin F, beta-thalassemia
      genotype, or risk factors for coronary artery disease. Three of the 5 patients
      with perfusion and ECG abnormalities (and another with only perfusion defects)
      developed a stress-induced sickling crisis. CONCLUSION: Physical stress may
      induce myocardial ischemia in sickle beta-thalassemia patients with normal
      coronary arteries and elicit painful crises. The sickling process, activated by
      exercise, could be the common underlying mechanism.

PMID- 11583638
TI  - Antibiotic use and risk of ischemic stroke in the elderly.
AB  - PURPOSE: To determine whether treating infections with antibiotics that have
      antichlamydial activity decreases the risk of ischemic stroke in the elderly.
      SUBJECTS: We analyzed data from 199 553 subjects 65 years and older in a health
      care claims database who had continuous health and pharmacy coverage for at least
      2 years between January 1, 1991, and September 30, 1997. Using proportional
      hazards models with time-dependent covariates for prior antibiotic prescription
      and adjusting for cardiovascular risk factors, we determined the associations
      between antibiotic use and first claim for ischemic stroke (n = 7,335) during the
      observation period. RESULTS: Rates of stroke (per 1,000 person-years) were 6.64
      for macrolides, 9.27 for quinolones, 7.49 for tetracyclines, 6.88 for
      penicillins, 7.97 for cephalosporins, 8.58 for trimethoprim-sulfamethoxazole, and
      7.29 for subjects with no antibiotic claims. The adjusted hazard ratios (HR) were
      0.94 (95% confidence interval [CI]: 0.87 to 1.01) for macrolides, 1.04 (95% CI:
      0.91 to 1.18) for tetracyclines, 1.02 (95% CI: 0.95 to 1.08) for penicillins, and
      1.00 (95% CI: 0.82 to 1.22) for trimethoprim-sulfamethoxazole. Subjects with
      claims for quinolone antibiotics (HR = 1.17; 95% CI: 1.09 to 1.26) and
      cephalosporins (HR = 1.09; 95% CI: 1.02 to 1.16) had a slightly higher risk of
      stroke. CONCLUSION: Exposures to short courses of antibiotics are not associated
      with lower risk of ischemic stroke in patients aged 65 years and older.

PMID- 11583639
TI  - Efficacy and safety of oral and early-switch therapy for community-acquired
      pneumonia: a randomized controlled trial.
AB  - PURPOSE: We sought to determine the safety, efficacy, and cost of oral therapy
      for patients with community-acquired pneumonia. In patients with nonsevere
      pneumonia, conventional (parenteral) treatment was compared with the oral route;
      in patients with severe pneumonia, conventional treatment was compared with early
      switch from parenteral to oral therapy. SUBJECTS AND METHODS: We randomly
      assigned 85 hospitalized patients with nonsevere pneumonia to one of two groups:
      41 received oral antimicrobials from admission, and 44 received parenteral
      antimicrobials until they had been afebrile for 72 hours before switching to oral
      treatment. We randomly assigned 103 patients with severe pneumonia who had
      initially been treated with parenteral antimicrobials to one of two groups: 48
      were switched to oral therapy after 48 hours of treatment (early switch), and 55
      received a full 10-day course of parenteral antibiotics. RESULTS: Among patients
      with nonsevere pneumonia, there were no deaths in the oral treatment group, and
      one death (2%) in the parenteral treatment group (95% confidence interval [CI]
      for between-group [oral minus parenteral] difference: -7% to 2%, P = 0.3). The
      time to resolution of morbidity was < or =5 days in 34 (83%) patients in the oral
      treatment group and 39 (88%) patients in the parenteral treatment group (P =
      0.5); there were treatment failures in 4 (10%) patients in the oral treatment
      group and 14 (32%) patients in the parenteral treatment group (P = 0.02). Among
      patients with severe pneumonia, there was one (2%) death in the early-switch
      group and no deaths in the full course of parenteral antibiotics groups (95% CI
      for between-group [early switch vs. full course] difference: -2% to 6%, P = 0.5).
      The time to resolution of morbidity was < or =5 days in 38 (79%) patients in the
      early-switch group and 41 (75%) in the full-course group (P = 0.3). There were 12
      (25%) treatment failures in the early-switch group and 13 (24%) in the full
      course group (P = 0.9). There were fewer adverse events in the oral and early
      switch groups, primarily due to lower rates of infusion-related phlebitis.
      Significant cost savings, mainly due to a shorter hospitalization, occurred among
      patients with severe pneumonia in the early-switch group. CONCLUSION: Inpatients
      with nonsevere community-acquired pneumonia can be effectively and safely treated
      with oral antimicrobials from the time of admission, whereas those with severe
      pneumonia can be treated with early-switch therapy.

PMID- 11583640
TI  - The evaluation of pleural effusions in patients with heart failure.
AB  - PURPOSE: To determine the causes of pleural effusions in patients with heart
      failure, and the association of the characteristics of these statistics with the
      use of diuretics. SUBJECTS AND METHODS: Eighty-one patients with a definite
      diagnosis of heart failure who underwent thoracentesis were evaluated. Fluids
      were classified as transudates or exudates using Light's criteria. RESULTS: Forty
      one effusions (in 34 patients) were transudates, and 54 (in 47 patients) were
      exudates. A specific cause was found for 32 of the exudates (27 patients); except
      for heart failure, no obvious cause was found for the remaining 22 fluids (20
      patients). Exudates with a specific cause for an exudate were more likely to have
      at least two of Light's criteria (18 of 27 [67%]) than did exudates without a
      known cause (2 of 21 [10%]). Intravenous diuretic therapy in the 24 hours before
      thoracentesis was significantly more common among patients with exudates without
      a specific cause. CONCLUSIONS: Patients with heart failure may have exudative
      pleural effusions without an obvious cause except heart failure.

PMID- 11583641
TI  - Factors associated with the occurrence and magnitude of earthquake-induced
      increases in blood pressure.
AB  - BACKGROUND: Blood pressure increases transiently after a major earthquake, but
      the characteristics and the mechanism of this increase are unknown. METHODS: The
      study involved 124 elderly hypertensive outpatients from two clinics near the
      epicenter of the Hanshin-Awaji earthquake (7.2 on the Richter scale) for whom
      ambulatory blood pressure monitoring and assessment of end-organ damage had been
      performed before the earthquake. RESULTS: During the 1 to 2 weeks after the
      earthquake, while major aftershocks persisted, mean (+/- SD) systolic blood
      pressure was 14 +/- 16 mm Hg greater and mean diastolic blood pressure was 6 +/-
      10 mm Hg greater, but these values returned to baseline by 3 to 5 weeks after the
      earthquake. The earthquake-induced increase in blood pressure correlated
      significantly with the "white coat" effect ([clinic systolic blood pressure minus
      24-hour systolic blood pressure] r = 0.34, P <0.001), body mass index (r = 0.28,
      P <0.001), and age (r = 0.24, P <0.01). The earthquake-induced blood pressure
      increase was prolonged in patients with microalbuminuria for at least 2 months
      after the earthquake, whereas it was less pronounced in patients who had been
      treated with an alpha-blocker and in patients with diabetes mellitus.
      CONCLUSIONS: These elderly patients with hypertension had a substantial increase
      in blood pressure after a major earthquake; the increase was usually transient,
      except in patients who had microalbuminuria. The correlation with white-coat
      hypertension suggests that both phenomena are related to sympathetic activation.

PMID- 11583642
TI  - I was sick and you came to visit me: time spent at the bedsides of seriously ill
      patients with poor prognoses.
AB  - PURPOSE: To learn how much time hospital staff and families spend at the bedsides
      of seriously ill patients with poor prognoses. SUBJECTS AND METHODS: An
      observational study was made of 58 inpatients with cancer, acquired
      immunodeficiency syndrome, heart failure, obstructive lung disease, or advanced
      dementia, along with their families and the physicians and nurses working on the
      medical floors of a university hospital, using direct videotape surveillance of
      patients' doorways. RESULTS: The mean (+/-SD) total visitor-minutes spent in the
      rooms of these patients was 321 +/- 297 minutes per day. On average, patients
      spent 18 hours 39 minutes per day alone. Mean visit durations were 3 +/- 3
      minutes for attending physicians (including consultants), 3 +/- 2 minutes for
      house officers, 2 +/- 1 minutes for nurses, and 24 +/- 51 minutes for family. The
      total person-visits per patient per day were 3 +/- 3 for attending physicians, 9
      +/- 8 for house officers, 45 +/- 23 for nurses, and 13 +/- 21 for family. Patient
      sex and age were not significantly associated with total visitor-minutes. In a
      repeated-measures analysis of variance model, nonwhite patients received fewer
      total visitor-minutes than did white patients, and patients with dementia
      received fewer total visitor-minutes than did patients with other diagnoses,
      especially those with malignancy. Do-not-resuscitate orders were associated with
      slightly more total visitor-minutes. CONCLUSIONS: These seriously ill patients
      with poor prognoses spent most of their time in the hospital alone. Staff visits
      were frequent but brief. These data do not confirm anecdotal reports that staff
      members spend less time at the bedsides of patients with do-not-resuscitate
      orders. Patients with advanced dementia and minority patients appear to have less
      bedside contact. Further study is required to confirm these findings and to
      understand optimal visit time for medical inpatients with poor prognoses.

PMID- 11583643
TI  - Clinically relevant differences between the statins: implications for therapeutic
      selection.
AB  - Although the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or
      statins, share a common lipid-lowering effect, there are differences within this
      class of drugs. The low-density lipoprotein (LDL) cholesterol-lowering efficacy,
      pharmacokinetic properties, drug-food interactions, and cost can vary widely,
      thus influencing the selection of a particular statin as a treatment option. The
      statins that produce the greatest percentage change in LDL cholesterol levels are
      atorvastatin and simvastatin. Atorvastatin and fluvastatin are least affected by
      alterations in renal function. Fewer pharmacokinetic drug interactions are likely
      to occur with pravastatin and fluvastatin, because they are not metabolized
      through the cytochrome P450 (3A4) system. The most cost-effective statins, based
      on cost per percentage change in LDL cholesterol levels, are fluvastatin,
      cerivastatin, and atorvastatin. Awareness of these differences may assist in the
      selection or substitution of an appropriate statin for a particular patient.

PMID- 11583644
TI  - Monday preference in onset of ischemic stroke.

PMID- 11583646
TI  - Measurement of health status after transmyocardial laser revascularization:
      critical but not the final answer.

PMID- 11583647
TI  - Hemoglobinopathies: an opportunity to study cardiac disease.

PMID- 11583648
TI  - Antibiotic use and occlusive stroke: weighing a negative result.

PMID- 11583649
TI  - Oral or intravenous-to-oral antibiotic switch therapy for treating patients with
      community-acquired pneumonia.

PMID- 11583650
TI  - The right time for end-of-life care.

PMID- 11583651
TI  - Quality in the making.

PMID- 11583652
TI  - Effect of Cr(VI) exposure on sperm quality: human and animal studies.
AB  - The semen status of male workers occupationally exposed to hexavalent
      chromium(VI) was investigated. Sperm counts from exposed workers were 47.05+/
      2.13 x 10(6)/ml and those from control group 88.96+/-3.40 x 10(6)/ml. Sperm
      motility decreased from 81.92+/-0.41% for the control group to 69.71+/-0.93% for
      the exposed workers. The levels of zinc, lactate dehydrogenase (LDH), and lactate
      dehydrogenase C4 isoenzyme (LDH-x) in seminal plasma for the exposed workers were
      1.48+/-0.07 micromol/ml, 1.05+/-0.02 x 10(3) U, and 0.47+/-0.01 x 10(3) U,
      respectively, which were significantly lower than those of 5.72+/-0.15
      micromol/ml, 1.49+/-0.02 x 10(3) U, and 0.78+/-0.15 x 10(3) U for the control
      group, respectively. Follicle stimulating hormone (FSH) (7.34+/-0.34 x 10(-3)
      IU/ml) in serum from the exposed workers was significantly higher than that
      (2.41+/-0.08 x 10(-3) IU/ml) from the control group. On the other hand, there
      were no significant differences in semen volume, semen liquefaction time,
      luteinizing hormone (LH) level in serum, and Cr concentration in both serum and
      seminal plasma between the exposed workers and the control group. Feeding Cr(VI)
      to rats significantly reduced the epididymal sperm counts from 87.40+/-3.85 x
      10(6)/g epididymis in control group to 21.40+/-1.20 x 10(6)/g epididymis at a
      CrO(3) dose of 10 mg/kg body weight and to 17.48+/-1.04 x 10(6)/g epididymis at a
      CrO(3) dose of 20 mg/kg body weight. Exposure of rats to Cr(VI) also
      significantly increased the sperm abnormality from 2.75+/-0.06% in the control
      group to 6.68+/-0.32% in the exposed group at a CrO(3) dose of 10 mg/kg body and
      to 7.6+/-0.15% at a CrO(3) dose of 20 mg/kg body weight. In exposed rats, there
      was visible disruption in germ cell arrangement near the walls of the
      seminiferous tubules. The diameters of seminiferous tubules in exposed rats were
      smaller. These results suggest that occupational exposure to chromium(VI) leads
      to alteration of semen status and may affect the reproductive success of exposed
      workers.

PMID- 11583653
TI  - Case-referent survey of young adults with mesothelioma: I. Lung fibre analyses.
AB  - OBJECTIVES: Our study aimed to determine the lung tissue concentration of
      asbestos and other mineral fibres by type and length in persons with mesothelioma
      aged 50 yr or less at time of diagnosis, compared to controls of similar age and
      geographical region. In this age group it was thought that most, but not all,
      work-related exposures would have been since 1970, when the importation of
      crocidolite, but not amosite, was virtually eliminated. METHODS: Eligible cases
      were sought from recent reports by chest physicians to the SWORD occupational
      disease surveillance scheme. Lung tissue samples were obtained at autopsy from 69
      male and four female cases, and mineral fibres identified, sized and counted by
      electron microscopy. Fibre concentrations per microg dry tissue were compared
      with similar estimates from a control series of autopsies of sudden or accidental
      deaths. Unadjusted, and adjusted odds ratios calculated by logistic regression,
      assessed relative risk in relation to fibre type, length and concentration.
      RESULTS: Unadjusted and adjusted odds ratios increased steadily with
      concentration of crocidolite, amosite, tremolite and all amphiboles combined.
      There was also some increase with chrysotile, but well short of statistical
      significance. Incremental risk examined in a linear model was as highly
      significant for all amphiboles together as individually. Short, medium and long
      amphibole fibres were all associated with increased risk in relation to length.
      Mullite and iron fibres were significant predictors of mesothelioma when
      considered without adjustment for confounding by amphiboles, but, after
      adjustment, were weak and far from statistically significant. CONCLUSIONS: In
      this young age group, amosite and crocidolite fibres could account for about 80%
      of cases of mesothelioma, and tremolite for some 7%. The contribution of
      chrysotile, because of low biopersistence, cannot be reliably assessed at
      autopsy, but to the extent that tremolite is a valid marker, our results suggest
      that it was small. The steep linear trend in odds ratio shown by amphiboles
      combined indicates that their effects may be additive, with increased risk from
      the lowest detectable fibre level. Non-asbestos mineral fibres probably made no
      contribution to this disease. Contrary to expectation, however, some 90% of cases
      were in men who had started work before 1970; this was so whether or not amosite
      or crocidolite was found in lung tissue.

PMID- 11583654
TI  - Case-referent survey of young adults with mesothelioma: II. Occupational
      analyses.
AB  - OBJECTIVES: Our study aimed to identify occupations at increased risk of
      developing mesothelioma in persons aged 50 yr or less, and to relate these
      occupations to lung tissue concentration of asbestos fibres by type. In this age
      group it was thought that most, but not all, work-related exposures would have
      been since 1970, when the importation of crocidolite, but not amosite, was
      virtually eliminated. METHODS: Eligible cases were sought from recent reports by
      chest physicians to the SWORD occupational disease surveillance scheme. Work
      histories were obtained for 115 men and 13 women, usually with the help of the
      chest physicians or coroners. Jobs were coded by the Office of National
      Statistics, so that the observed years spent in each occupation could be compared
      with expected values from census data, 1960-90. Lung tissue samples were obtained
      at autopsy from 69 male and four female cases, and mineral fibres identified,
      sized and counted by electron microscopy. RESULTS: Of 37 industrial occupations
      analysed, odds ratios were significantly raised in eight: five in the
      construction industry and the others in shipbuilding, the manufacture of cement
      products and the manufacture of non-metallic mineral products (including
      asbestos). The concentrations in lung of crocidolite and amosite fibres, which
      together could account for 80-90% of cases, did not differ between occupational
      categories; those for amosite were appreciably higher than for crocidolite.
      Tremolite fibres were rarely found. CONCLUSION: Mesothelioma in this young age
      group is dominated by carpenters, plumbers, electricians and insulators in the
      construction industry, and is mainly attributable to amphibole exposure. Work in
      shipbuilding and manufacture of mineral products was less important than in
      earlier studies. Contrary to expectation, however, some 90% of cases were in men
      who had started work before 1970.

PMID- 11583655
TI  - Simultaneous assessment of occupational exposures from multiple worker groups.
AB  - The methods developed by Rappaport et al. [Ann. Occup. Hyg. 39 (1995) 469] and
      Lyles et al. [J. Agri. Bio. Environ. Stat. 2 (1997a) 64; Ann. Occup. Hyg. 41
      (1997b) 63]) for assessing workplace exposures on a group-by-group basis are
      extended to allow for the simultaneous assessment of data from multiple worker
      groups within the same industry. These extended methods allow models to be fit
      simultaneously to data on all groups in a study, even when some of the groups
      might not contribute adequate information to be modeled separately. We assume
      that the exposures are log-normally distributed, and that they can be adequately
      modeled by a mixed effects regression model with parameters for exposure levels
      and for between- and within-worker variance components. Simultaneously analyzing
      data from multiple groups is only advantageous when at least one of these
      variance components can be assumed to be homogeneous across the groups. Here, we
      advocate testing an assumption of homogeneous within-worker variance components,
      sigma(2)(w,h), using a likelihood ratio test to choose between a full model
      (distinct sigma(2)(w,h) for each group) and a reduced model (common sigma(2)(w)
      across groups). We then develop a procedure, which is conditional on the results
      of the likelihood ratio test, for testing whether or not each group of workers is
      overexposed to the contaminant of interest. This modeling and testing procedure
      was applied to 39 different data sets, each containing data for multiple groups,
      from a wide variety of industries. For these data, the testing procedure
      generally resulted in the same conclusion regarding overexposure under both
      models, even in those data sets where the within-worker variance components
      appeared to be quite heterogeneous. We also conducted a small simulation study to
      estimate the significance level of the proposed testing procedure, and found that
      the significance levels tended to be adequately close to the specified nominal
      level when a likelihood ratio test with significance level of at least 0.01 was
      used as a preliminary test. Additionally, we make specific recommendations for
      designing studies and suggest a method for determining whether engineering and
      administrative controls or individual-level interventions would be of most
      benefit to an overexposed group of workers.

PMID- 11583656
TI  - Proposal for an approach with default values for the protection offered by PPE,
      under European new or existing substance regulations.
AB  - Introduction of personal protective equipment (PPE) in the process of
      quantitative exposure and risk assessment should be addressed carefully. PPE
      which have been designed and manufactured according to CE-criteria and have
      proved to pass relevant test criteria, can be classified as "proper functioning".
      However, test criteria for PPE are not equal to levels of protection which can be
      achieved in the workplace, because actual workplace exposure scenarios, fit,
      maintenance and storage may differ substantially from the test conditions. The
      proper use of PPE is related to issues which form a part of a PPE-programme. Such
      a programme should be implemented in a company to ensure selection of proper PPE
      and information, training and instruction of employees how to wear PPE properly.
      Assigned protection factors (APFs) for different designs of respiratory
      protective devices (RPD) have been introduced to quantify effectiveness of RPD in
      the workplace. Similar APFs are proposed for dermal protection (gloves and
      clothing). In general biological monitoring studies show lower reduction of
      internal exposure than estimated by reduction of external exposure. Therefore,
      conservative estimates of protection by PPE, i.e. the lowest APFs, are proposed
      for risk assessment purposes if "proper use of proper functioning" PPE as part of
      a PPE-programme cannot be demonstrated.

PMID- 11583657
TI  - A new approach to sampling for particle size and chemical species
      "fingerprinting" of workplace aerosols.
AB  - A commercially-available, high-volume (28.3 Lpm) Andersen-type cascade impactor
      was modified in order to extend its operational range further into the range of
      large inhalable particles for purposes of use in an exposure assessment study in
      the primary nickel production industry. The modification involved incorporating a
      10-ppi (pores per inch) porous plastic foam top stage that has a wide penetration
      curve with a (50)d(ae)-value of approximately 27 microm. This enabled the upper
      end of the range of the instrument to be extended from about 10 to greater than
      70 microm. The inlet of the original instrument was also modified to incorporate
      the new top stage and provide "representative" aspiration of total airborne
      particulate with an efficiency of close to 100% over the range of aerodynamic
      particle sizes of interest. A mathematical inversion algorithm developed in
      earlier research was modified so that it could be applied to this new instrument.
      This enabled raw data on particulate material recovered from all stages of the
      instrument (including the new porous foam top stage) to be used for the
      determination of continuous particle size distributions, as well as chemical
      speciation, over the inhalable range. The new instrument was deployed in a pilot
      field study in the nickel primary production industry by which to demonstrate the
      potential of the new instrument for generating useful information pertaining to
      health-relevant aerosol size tractions (e.g., inhalable, thoracic, and
      respirable), and for soluble, sulphidic, metallic, oxidic and total nickel
      chemical species groups.

PMID- 11583658
TI  - A model for predicting endotoxin concentrations in metalworking fluid sumps in
      small machine shops.
AB  - METHODS: In British Columbia, Canada, nineteen small machine shops which used
      water-based metalworking fluids (MWF) were examined. One bulk MWF sample was
      taken from each independent sump (N=140) and tested for endotoxin using the
      Limulus Amoebocyte Lysate assay. Factors that might influence the MWF sump
      endotoxin concentration were investigated using mixed effect multiple regression
      modelling to control for repeated measures within shops. RESULTS: The geometric
      mean (GM) endotoxin concentration was 6791 EU/ml. Contamination of MWF with tramp
      oil, MWF pH, MWF temperature, and MWF type were significant predictors of sump
      fluid endotoxin concentration (model P=0.0001, ordinary least squares R(2)
      =0.36). Concentrations of endotoxin in sump fluids were increased by MWF
      contamination with tramp oils such as hydraulic oils, preservative oils, spindle
      oils, slidway lubricants, gear lubricants, and greases (model predicted GM=17400
      EU/ml vs. 1600 EU/ml without tramp oil). Concentrations were also elevated where
      pH was lower than 8.5 (predicted GM=10600, vs 3600 EU/ml for pH 8.5 to 9.5),
      where soluble fluids were used (predicted GM=11800 vs. 2800 EU/ml for synthetic
      fluids), and where sump fluid temperatures were higher (predicted GM=2600 EU/ml
      at 11 degrees C vs. 21500 EU/ml at 32 degrees C). The within-shop correlation of
      sump bulk fluid endotoxin concentrations was 38%. CONCLUSIONS: Minimizing tramp
      oil contamination, using synthetic fluids, and monitoring pH and temperature
      would be valuable tools for controlling endotoxin contamination in MWF sumps. In
      addition, since there was correlation within-shop, contamination of one sump in a
      shop may suggest changing the fluids in all.

PMID- 11583659
TI  - Assessment of exposure to organic dust in a hemp processing plant.
AB  - The aim of this preliminary study was to assess exposure to various constituents
      of the organic dust generated during the processing of hemp in a small group of
      exposed workers. Airborne levels of inhalable dust, endotoxin and soluble
      protein, and the respirable, thoracic and inhalable fractions of fungal,
      bacterial and actinomycete contamination were measured in the personal breathing
      zone of exposed workers. Inhalable dust, endotoxin, fungal and bacterial
      contamination all exceeded levels found in similar vegetable fibre processing
      factories, since inhalable dust levels ranged from 10.4 to 79.8 mg/m(3) and
      inhalable bacterial levels between 4.7 and 190 x 10(6) cfu/m(3). Soluble protein
      and endotoxin (r=0.99, P<0.0001), endotoxin and inhalable dust (r=0.94, P<0.005)
      and inhalable dust and protein (r=0.98, P<0.0001) were significantly correlated,
      suggesting that there was little variation in the composition of the dust from
      different sites or activities around the workplace. Andersen sampling gave an
      indication of background microbe levels, although no attempt was made to identify
      the specific microorganisms as all plates were significantly overgrown. Airborne
      assessments demonstrated that exposures were highly task specific. For example,
      sweeping the floor generated the highest exposure levels of total dust, protein,
      endotoxin, bacteria and fungi. Therefore, we have shown that a modern-day hemp
      fibre processing plant produces significant quantities of respirable dust which
      is highly contaminated with endotoxin and microorganisms. This organic dust has
      the potential to cause a range of ill health problems.

PMID- 11583660
TI  - Determinants of exposure to respirable quartz dust in the construction industry.
AB  - Because most masonry building materials contain quartz and because these
      materials are subjected to a variety of treatments during the building process,
      quartz is encountered everywhere in building operations. The level of exposure to
      respirable quartz has been measured for some highly exposed groups of employees.
      At 30 construction sites personal air sampling (PAS) measurements of respirable
      dust and quartz have been performed and 171 samples have been taken. Both
      respirable dust and quartz levels were high. Respirable quartz exposures of more
      than ten times the Dutch limit value of 0.075 mg/m(3) TWA were common, but
      exposures up to 200 times the Dutch limit value were also found. The measurements
      were task oriented. By statistical analysis the contribution of the different
      determinants to the total exposure has been identified. With this approach,
      directions for an effective control measures programme can be given.

PMID- 11583661
TI  - Ultraviolet radiation emitted by CO(2) arc welding.
AB  - The arcs associated with arc welding emit high levels of ultraviolet radiation
      (UVR), and this often causes acute injuries in the workplace, particularly
      photokeratoconjunctivitis. It is important to know the level of UVR emitted by
      arc welding under various conditions, as this information will help in evaluating
      potential UVR hazards in welding workplaces and taking protective measures
      against it. In this study, the ACGIH effective irradiance for UVR was measured
      experimentally for CO(2) arc welding in order to evaluate its UVR hazards. A
      welding robot was used in the experiment in order to realize reproducible and
      consistent welding operations. The effective irradiance at 1 m from the arc was
      in the range 0.28-7.85 W/m(2) (28-785 microW/cm(2)) under the study conditions.
      The corresponding permissible exposure time per day is only 4-100 s, suggesting
      that UVR from CO(2) arc welding is actually hazardous for the eye and skin. It
      was found that the effective irradiance is inversely proportional to the square
      of the distance from the arc, is strongly dependent on the direction of emission
      from the arc with a maximum at 50-60 degrees from the plate surface, and tends to
      increase with welding current.

PMID- 11583662
TI  - Variations in exposure to inhalable wood dust in the Danish furniture industry.
      Within- and between-worker and factory components estimated from passive dust
      sampling.
AB  - Variability of exposure to wood dust at large factories in the Danish furniture
      industry was studied. Three repeated exposure measurements of 292 workers at 38
      factories were included in the study. The measurements were carried out by use of
      personal passive dust monitors. The components of variance were estimated by
      means of a random effects ANOVA model. The ratio of within- to between-worker
      variance was 1.07. Based on this result, and three repeated exposure
      measurements, the observed relation between health outcome and exposure will be
      attenuated to 74% of the true value. Grouping by factory showed very poor
      exposure contrast, as the contrast in exposure level among factories was as low
      as 0.15.

PMID- 11583663
TI  - Dynamic asymmetries in convergence eye movements under natural viewing
      conditions.
AB  - PURPOSE: To clarify differences in the dynamics of convergence eye movements in
      response to symmetrical stimuli between the dominant eye and the nondominant eye
      under natural viewing conditions. METHODS: This study was conducted in 11 normal
      volunteers (age range, 22-30 years). The subject was seated on a chair, and the
      head was fixed using a bite-block. The dominant eye was determined with the "hole
      in-the-card" test. Horizontal positions of the eyes were recorded using an
      infrared reflection device. Recordings of right eye movements were subtracted
      from left eye movements to obtain the vergence response. The fixation target was
      moved toward the center of both eyes from 50 to 20 cm in front of the face at a
      constant velocity in five steps (20, 30, 40, 50, and 60 cm/s). The target was
      moved by a pulse motor controlled by a microcomputer. The dynamic properties of
      each eye movement and the vergence components were analyzed. RESULTS: At
      velocities < or =40 cm/s, convergence responses consisted of two components: the
      fusion-initiating component and the fusion-sustaining component. The fusion
      initiating component drove the initial faster dynamic portion of the response,
      and the fusion-sustaining component maintained the latter slower dynamic portion
      of the response. The mean peak velocity of the fusion-initiating component was
      significantly greater in the dominant eye than in the nondominant eye. The mean
      peak latency of the catch-up component was significantly shorter in the dominant
      eye than in the nondominant eye. CONCLUSIONS: The present study indicated that
      the trajectory of convergence eye movement under natural viewing conditions
      consists of two components, the fusion-initiating component and the fusion
      sustaining component, and that the convergence response to symmetric stimuli was
      asymmetric between the dominant eye and the nondominant eye during the fusion
      initiating phase. The neural control system of convergence eye movements
      preferentially drives the dominant eye during the fusion-initiating phase of the
      response.

PMID- 11583664
TI  - Facial nerve anatomy in eyelids and periorbit.
AB  - PURPOSE: To clarify anatomically the facial nerve branches in the eyelids and
      periorbit. METHODS: The facial nerve branches of the left periorbits from 31
      Japanese cadavers were dissected under a surgical microscope. RESULTS: The
      temporal, zygomatic, and deep buccal branches assembled posterior to the
      orbicularis oculi from its temporal or inferior side, and formed a dense plexus.
      The superficial buccal branches coursed, unlike the others, around the inferior
      nasal margin of the orbicularis oculi with some variations. The branches always
      passed across the "triangular window" that was outlined by the orbicularis oculi,
      the zygomaticus minor, and the levator labii superioris alaeque nasi. Then the
      branches crossed over the medial palpebral ligament, reaching both the procerus
      and corrugator supercilii in 94% of the specimens. The branches ramified the
      lower part of the orbicularis oculi in 65% and the upper part in 42% of the
      specimens. CONCLUSIONS: The superficial buccal branches are the main supplier to
      the muscles in the nasal periorbit. This anatomical finding may be important
      information for accurate procedures in facial nerve surgery.

PMID- 11583665
TI  - Rapid injection of indocyanine green dye for evaluation of choroidal venous
      circulation.
AB  - PURPOSE: The purpose of this study was to investigate the effects of rapid
      intravenous administration of a small bolus of indocyanine green (ICG) dye on
      early phase findings of ICG angiography. METHODS: Rabbit eyes were used. Ten
      normal eyes, 5 eyes with occlusion of vortex veins, and 5 eyes with chorioretinal
      atrophy were examined by ICG angiography, and early-phase findings after a rapid
      injection of a small bolus of dye were compared with those obtained with an
      ordinary injection. RESULTS: In normal eyes, after the rapid injection it was
      possible to visualize some small bright fluorescent boluses in the choroidal
      veins from 6 to 12 seconds after injection, while with the ordinary injection
      they were unclear. In eyes with occlusion of vortex veins, the rapid injection
      resulted in visualization of the choroidal veins with delayed filling against the
      background, and the region of the choroidal veins with delayed filling could
      easily be determined. In eyes with chorioretinal atrophy, only the rapid
      injection clearly revealed the choroidal veins with delayed filling. CONCLUSIONS:
      The rapid injection made it possible to detect the choroidal veins with delayed
      filling that were not clearly and easily visible using an ordinary injection.
      Rapid injection of ICG dye is useful for a detailed examination of choroidal
      circulation.

PMID- 11583666
TI  - Differentiation of Th1 and Th2 cells in lymph nodes and spleens of mice during
      experimental autoimmune uveoretinitis.
AB  - PURPOSE: Experimental autoimmune uveoretinitis (EAU) is a T-cell-mediated
      autoimmune disease that can be elicited in susceptible rodent strains by
      immunization with a retinal autoantigen, such as interphotoreceptor retinoid
      binding protein (IRBP). In this study, we investigated whether there is a
      correlation between inflammation in the eye and T-helper (Th)1- and Th2-type
      responses in the lymph nodes and the spleen after immunization of B10.A mice with
      IRBP. METHODS: B10.A mice were immunized with IRBP emulsified with complete
      Freund's adjuvant (CFA), and eyes were then enucleated for histological
      examination of EAU at 1, 2, 4, 6, or 8 weeks after immunization. In addition,
      lymph node cells and spleen cells were collected, and cultured with IRBP to
      measure T-cell proliferation responses and Th1-type (interleukin [IL]-2,
      interferon [IFN]-gamma), Th2-type (IL-4, IL-10) cytokine production. RESULTS:
      Pathologically, severe ocular inflammation occurred 2 weeks after IRBP
      immunization, persisted for 2 weeks, and then gradually resolved. Interleukin-2
      and IFN-gamma production were observed in draining lymph node cells at 1 and 2
      weeks after IRBP immunization. Those responses then diminished, whereas IFN-gamma
      production by spleen cells was observed from week 1, peaked at week 4, and
      gradually decreased. Alternatively, significant production of IL-4 or IL-10 by
      draining lymph node cells was not detected at any time point. Both IL-4 and IL-10
      production by spleen cells was observed at week 6. CONCLUSIONS: Th1-type
      responses were observed early in draining lymph nodes, then in the spleen after
      IRBP immunization. The levels of IFN-gamma production by spleen cells reflected
      the severity of EAU, confirming their pathogenic role in this disease. Th2-type
      responses were generated in the spleen only as the disease receded, suggesting a
      role for Th2 cells in the spontaneous termination of EAU.

PMID- 11583667
TI  - TIMP-1 production by bovine retinal pigment epithelial cells increases in
      response to cyclic mechanical stretch.
AB  - PURPOSE: The effect of mechanical stretch was examined on cultured retinal
      pigment epithelial (RPE) cells in order to observe changes in their production of
      tissue inhibitor of metalloproteinase-1 (TIMP-1) and vascular endothelial growth
      factor (VEGF) in response to physiological strain. METHODS: Bovine RPE cells in
      near-confluent culture were exposed to mechanical stretch of the bottom of a 6-cm
      petri dish at the maximum magnitude of 4500 microstrain and at a cycle of 30
      seconds for 72 hours. TIMP-1 and VEGF levels in the medium following 24, 48, and
      72 hours of cyclic stretch were measured by enzyme immunoassay. RESULTS: The
      growth of RPE cells during the 72-hour period of stretching did not show a
      significant difference from that of nonstretched control cells. RPE cells in the
      stretched group produced a significantly larger amount of TIMP-1 at 48 and 72
      hours after stretch, compared with nonstretched control (P =.044 and P =.027,
      respectively, Student t-test). The levels of VEGF produced by RPE cells were not
      significantly different between the stretched group and nonstretched control
      group. CONCLUSIONS: The secretion of TIMP-1 by bovine RPE cells was enhanced by
      cyclic mechanical stretch. Mechanical strain is one factor in regulating the
      secretion of TIMP-1 by RPE cells.

PMID- 11583668
TI  - Effects of superior colliculus inhibition on three-dimensional visual motion
      processing in the lateral suprasylvian visual area of the cat.
AB  - PURPOSE: To determine whether visual inputs from the tectothalamocortical pathway
      influence three-dimensional motion processing within the lateral suprasylvian
      (LS) area of the cat. METHODS: Tungsten microelectrodes were used for recording
      visual-evoked potentials (VEPs) from the LS area of 4 cats. Random dot
      stereograms were used as visual stimuli. Three-dimensional, motion-triggered VEPs
      were recorded from the LS area. Each motion sequence consisted of an abrupt onset
      of motion disparity with a 2 degrees amplitude followed by an abrupt offset and a
      stationary phase of 900 ms. The velocity of the motion disparity was varied in
      eight steps from 10 degrees to 400 degrees per second. The onset of motion
      disparity was used as the trigger for recording the VEPs. Single or multiple
      injections (two to three) of muscimol were made mainly into the rostral superior
      colliculus (SC). The amplitudes of the VEPs before and after the muscimol
      injection were compared. RESULTS: A large negative wave ( N1) with an implicit
      time of 92.7 +/- 13.5 ms (mean +/- SD, n = 98) was recorded consistently. The
      amplitude of N1 was significantly larger on stereovision of motion disparity than
      on either binocular vision of two-dimensional lateral motion or monocular vision,
      indicating that N1 contains neurons sensitive to motion disparity. The amplitude
      of N1 was not altered by muscimol injection into the SC at velocities < or =50
      degrees/s. On the other hand, the amplitude of N1 was reduced to 66-71% of that
      observed before muscimol injection at velocities > or =75 degrees/s. CONCLUSIONS:
      These findings suggest that the LS area processes three-dimensional motion inputs
      via two parallel pathways, the geniculostriate pathway and the
      tectothalamocortical pathway, at velocities of motion disparity > or =75
      degrees/s, while the three-dimensional motion inputs project to the LS area only
      via the geniculostriate pathway at velocities of motion disparity < or = 50
      degrees/s.

PMID- 11583669
TI  - Treatment of A-pattern esotropia with marked mongoloid slanting palpebral
      fissures.
AB  - BACKGROUND: The association of oblique palpebral fissures and A- or V-pattern has
      not been clarified. We report two cases of A-pattern esotropia with marked
      mongoloid slanting palpebral fissures associated with vertical displacement of
      the horizontal rectus muscle. CASES: Case 1 was a boy with Prader-Willi syndrome.
      He showed A-pattern esotropia with upward slanting palpebral fissures. Severe
      superior oblique muscle overaction was observed. Case 2 was a girl with
      meningocele. She also showed A-pattern esotropia with upward slanting palpebral
      fissures. OBSERVATIONS: In case 1, weakening surgery of the superior oblique
      muscles did not improve the A-pattern. Coronal images of computed tomography
      showed one-half-muscle-width upward displacement of both lateral rectus muscles.
      After downward transposition surgery of the lateral rectus muscles, the
      preoperative A-pattern of 25 prism diopters (PD) was successfully corrected to 10
      PD. In case 2 also, upward displacement of both lateral rectus muscles was shown
      by computed tomography. The preoperative A-pattern of 26 PD was corrected to 4 PD
      postoperatively after upward transposition surgery of the medial rectus muscles.
      CONCLUSIONS: The vertical displacement of horizontal rectus muscles was
      considered the principal cause of A-pattern in these cases associated with marked
      mongoloid slanting palpebral fissures.

PMID- 11583670
TI  - Comparison of two procedures: photorefractive keratectomy versus laser in situ
      keratomileusis for low to moderate myopia.
AB  - PURPOSE: A prospective study was conducted to compare the effectiveness, safety,
      and stability of photorefractive keratectomy (PRK) and laser in situ
      keratomileusis (LASIK) for correction of low to moderate myopia. METHODS: Forty
      five patients with a manifest refraction (PRK, -4.54 +/- 0.80; LASIK, -4.82 +/-
      1.10) from -1.50 to -6.00 diopters (D) were treated and followed-up for 6 months.
      In each case, 1 eye received PRK and the other LASIK. The first eye treated, and
      the surgical method used in the first eye, were randomized. Uncorrected and
      corrected visual acuity, manifest refraction, corneal haze, and topographic
      analysis of ablation decentration were examined. RESULTS: The uncorrected visual
      acuity was 20/20 or better in 35 PRK eyes (77.8%) and 28 LASIK eyes (62.2%) at 6
      months (P =.107). At 6 months, 28 eyes (62.2%) that received PRK showed a
      spherical equivalent of within +/-0.5 D as compared with 24 eyes (53.4%) that
      received LASIK (P =.393). The amount of ablation decentration was 0.37 +/- 0.25
      mm in PRK eyes and 0.49 +/- 0.38 mm in LASIK eyes at 3 months (P =.36).
      CONCLUSIONS: In our study, PRK and LASIK were found to be similarly effective and
      predictive of correction in low to moderate myopia. PRK has the advantage of less
      ablation decentration and is safer than LASIK, so we recommend PRK for eyes with
      low to moderate myopia.

PMID- 11583671
TI  - Factors contributing to corneal complications after vitrectomy in diabetic
      patients.
AB  - PURPOSE: To elucidate factors contributing to corneal complications after
      vitrectomy in diabetic patients. METHODS: The records of a series of 129 diabetic
      patients (202 eyes) who underwent pars plana vitrectomy performed by a single
      surgeon between March 1997 and February 1999 were analyzed retrospectively.
      Logistic regression analysis was performed to determine possible factors
      contributing to corneal complications. RESULTS: Of the 202 eyes, 102 (50.5%)
      developed corneal complications after surgery; 90 (44.6%) had epithelial
      disturbance; and 48 (23.8%) had corneal edema. The degree of surgical invasion
      during vitrectomy was significantly correlated with the occurrence of epithelial
      disturbance and corneal edema. CONCLUSION: Surgical invasion is a risk factor for
      corneal complications after vitrectomy in diabetic patients.

PMID- 11583672
TI  - Multi-layer amniotic membrane graft for pterygium in a patient with xeroderma
      pigmentosum.
AB  - BACKGROUND: Xeroderma pigmentosum (XP) is a rare, autosomal recessive,
      premalignant condition of the skin, and is reported to be associated with ocular
      surface disorders such as conjunctival malignancy and pterygium. Herein, we
      report a case of successful management of pterygium with multi-layer amniotic
      membrane graft (AMG) in a young XP patient. CASE: An 11-year-old Japanese girl,
      who had been diagnosed as having XP, was referred to us for treatment of her
      bilateral pterygium. Surgical intervention was attempted for a temporal,
      presumably fast-growing pterygium in her left eye. Multi-layer amniotic membrane
      grafting was performed. OBSERVATIONS: The surgery-induced pain and irritation
      disappeared within a day. The limbal conjunctival autograft survived on the AMG
      and re-epithelialization over the AMG was completed in 2 weeks. Best corrected
      visual acuity improved from 20/32 to 20/16 one month postoperatively. During the
      1-year follow-up period, no recurrence was noted. CONCLUSIONS: The present case
      exemplifies that AMG as an adjunct to primary pterygium resection is effective
      even in a young patient with XP. In addition, multi-layer AMG, which we first
      demonstrated in this report, seems to be useful for protecting bare sclera and
      extraocular muscles from mechanical injury.

PMID- 11583673
TI  - Surgical outcomes of trabeculotomy combined with sinusotomy for juvenile
      glaucoma.
AB  - PURPOSE: To evaluate the outcome of trabeculotomy combined with sinusotomy for
      juvenile glaucoma. METHODS: We studied 16 patients (25 eyes) (age range, 11-50
      years) with juvenile glaucoma for a minimum follow-up period of 1 year. We
      performed combined trabeculotomy and sinusotomy surgery in 13 juvenile glaucoma
      patients (18 eyes), and trabeculotomy alone in 6 patients (7 eyes). RESULTS: The
      intraocular pressure (IOP) of the combined surgery group was 29.8 +/- 7.8 mm Hg
      before surgery and 15.6 +/- 3.0 mm Hg 1 year after surgery. The IOP of the
      trabeculotomy-alone group was 29.1 +/- 6.4 mm Hg before surgery and 15.4 +/- 2.4
      mm Hg 1 year after surgery. A postoperative IOP spike that was higher than the
      preoperative IOP was recorded in 2 eyes of the combined surgery group and in 2
      eyes of the trabeculotomy group. The combined surgery group consisted of 7 eyes
      with a previously failed glaucoma surgery, and 11 eyes having a first glaucoma
      surgery. The postoperative IOP in these 11 eyes was 15.5 +/- 2.8 mm Hg.
      CONCLUSION: Trabeculotomy is very effective in lowering the IOP in patients with
      juvenile glaucoma. Sinusotomy does not play an important role in tension control.

PMID- 11583674
TI  - Comparison of detectability of visual field abnormality by frequency doubling
      technology in primary open-angle glaucoma and normal-tension glaucoma.
AB  - PURPOSE: To compare the effectiveness of frequency doubling technology (FDT) in
      detecting abnormalities in primary open-angle glaucoma (POAG) and in normal
      tension glaucoma (NTG). METHODS: Twenty-nine POAG patients (29 eyes) and 27 NTG
      patients (27 eyes) were studied. All subjects underwent testing with program C-20
      of FDT with appropriate corrective lenses. RESULTS: No significant differences
      were observed between the two groups in mean age, mean deviation (MD), and
      pattern standard deviation (PSD) measured by the Humphrey Field Analyzer (HFA).
      The correlation between MD values determined by HFA (x) and FDT (y) is
      represented by y = 0.60x - 2.7 (r = 0.78, P <.01) in the POAG group and y = 0.59x
      + 0.6 (r = 0.81, P <.001) in the NTG group. Although the average MD measured by
      FDT was significantly lower in the POAG group than in the NTG group (P <.05), no
      significant difference was found in average PSD between the two groups. In early
      glaucoma cases (MD > or = -5 dB by HFA), a larger proportion of cases in the POAG
      group than in the NTG group had lower significance level of MD determined by FDT
      than by HFA (P <.02). At many test points on the temporal periphery in the FDT,
      the mean sensitivity was lower in the POAG group than in the NTG group; whereas
      no significant differences among HFA test points were observed. CONCLUSIONS:
      Frequency doubling technology detected visual field abnormalities in POAG cases
      more sensitively than in NTG cases. This finding indicates that the pathogenesis
      of My-cell damage is rather different in POAG and NTG.

PMID- 11583675
TI  - Histologic examination of dislocated lenses.
AB  - PURPOSE: To examine histological changes resulting from dislocated and subluxated
      lenses. CASES: The subjects consisted of 16 patients (aged 52-89 years) who
      underwent total lens extraction for lens dislocation or subluxation in the
      Department of Ophthalmology at Fukui Medical University during the period between
      April 1991 and June 1998. There were 5 patients (6 eyes) with traumatic
      dislocation and 11 patients (11 eyes) with idiopathic dislocation. RESULT:
      Rupture of the cortical fibers and migration of the epithelial cells toward the
      posterior pole of the lens were more frequently noted in patients with traumatic
      dislocation than in the idiopathic group, and both findings were often
      simultaneously observed. Rupture of the cortical fibers was considered
      attributable to external pressure transmitted to the lens. CONCLUSION: We
      speculate that the concurrent migration and dislocation of the equatorial bow
      architecture toward the posterior pole was caused by inhibition of
      differentiation of the epithelial cells to fiber cells by external pressure on
      the equatorial region.

PMID- 11583676
TI  - Multifocal electroretinograms in patients with branch retinal artery occlusion.
AB  - PURPOSE: We recorded multifocal electroretinograms (M-ERG) in patients with
      branch retinal artery occlusion (BRAO) and compared the waveforms in the area of
      retinal artery occlusion with those in the normal area, to evaluate the influence
      of the damage to the inner retina shown by M-ERG responses. METHODS: Three
      patients who had normal visual acuity and visual field loss of more than one
      quadrant due to BRAO were examined. The central 50 degrees of ocular fundus was
      stimulated through dilated pupils by an array of 103 hexagonal elements for 4
      minutes. The waveforms of the first order and second order kernel responses of M
      ERG in the area of the retinal artery occlusion were compared with those of the
      vertically symmetrical, normally perfused area of the same eye. RESULTS: The
      amplitude of the averaged tracing decreased in the first negative wave (N1),
      first positive wave (P1), and second negative wave (N2) in the first order kernel
      responses in the area of retinal artery occlusion in comparison with the normally
      perfused area. Furthermore, prolongation of latency was noted for N1, P1, and N2
      in the same area. Second order kernel responses were not detected in the area of
      the retinal artery occlusion. CONCLUSIONS: The damage to the inner retina
      affected parts of N1, P1, and N2 of the first order kernel responses, with N2
      being the most seriously affected. Furthermore, second order kernel responses
      clearly reflected the condition of the inner retina.

PMID- 11583677
TI  - Subclassification of preproliferative diabetic retinopathy and glycemic control:
      relationship between mean hemoglobin A1C value and development of proliferative
      diabetic retinopathy.
AB  - PURPOSE: We evaluated the relationship between long-term glycemic control and the
      proportion of patients developing proliferative diabetic retinopathy (PDR) among
      cases with mild type preproliferative diabetic retinopathy (PPDR). METHODS: The
      relationship was evaluated between the mean hemoglobin A1C (HbA1C) value during a
      period of at least 2 years and the proportion of patients developing PDR among
      cases with mild type PPDR, based on our previously proposed subclassification.
      RESULTS: During follow-up, 27% of the total PPDR cases developed PDR. The mean
      HbA1C value in those patients who had developed PDR was 9.4% and was
      significantly higher than the 7.6% in those who had not developed PDR. The
      proportion developing PDR was 48% of the cases with a mean HbA1C value of 8.6% or
      more. By comparison, the proportion developing PDR was 8% among those with a mean
      HbA1C value below 8.6%. The proportion developing PDR was estimated to
      approximately double with each 1% increase in the mean HbA1C value. The
      cumulative occurrence rates of PDR at 2, 5, and 10 years were estimated to be 5%,
      28%, and 60% in cases with a mean HbA1C value of 8.6% or more, and 0%, 7%, and
      14% in those with a mean HbA1C value below 8.6%, respectively. CONCLUSION:
      Stricter systemic and ophthalmological control is indicated for cases with a mean
      HbA1C value exceeding 8.6%.

PMID- 11583678
TI  - The influence of sex difference in measurements with the Langham Ocular Blood
      Flow System.
AB  - PURPOSE: To assess sex difference and parameters possibly accounting for such a
      difference in healthy subjects evaluated by means of the Langham Ocular Blood
      Flow (OBF) System. METHODS: Pulse amplitude of intraocular pressure (IOP) and
      pulsatile ocular blood flow (POBF) as measured with the Langham OBF System were
      assessed in 86 healthy men and 69 healthy women. RESULTS: Compared to men, women
      showed higher POBF (mean +/- SD: 722.6 +/- 152.8 versus 647.8 +/- 164.9
      microL/min; P =.0056) and pulse amplitude (mean +/- SD: 2.3 +/- 0.7 versus 2.0 +/
      0.6 mm Hg; P =.0043) values. Sex difference was still significant after
      correcting for age, refraction, blood pressure, IOP, and pulse rate. Pulse
      amplitude correlated negatively with pulse rate, and POBF correlated negatively
      with IOP. Women had higher readings in pulse amplitude and POBF, even after
      correcting for age, refraction, IOP, blood pressure, and pulse rate. CONCLUSIONS:
      While using the Langham OBF System, one needs to be aware of sex difference that
      is independent of other hemodynamic parameters. How the observed difference in
      POBF is related to ocular blood flow, and how it might influence the
      preponderance of various ocular diseases in men or women remains to be clarified.

PMID- 11583679
TI  - Adult-onset foveomacular vitelliform dystrophy with retinal folds.
AB  - BACKGROUND: Adult-onset foveomacular vitelliform dystrophy is characterized by a
      solitary, oval, slightly elevated, yellowish subretinal lesion of the fovea. We
      examined a patient with adult-onset foveomacular vitelliform dystrophy with
      stellate retinal folds by optical coherence tomography and scanning laser
      ophthalomoscopy. CASE: A 58-year-old Japanese woman with a complaint of decreased
      vision in her right eye was diagnosed as having adult-onset foveomacular
      vitelliform dystrophy. OBSERVATIONS: Ophthalmoscopic examination revealed a
      yellowish lesion of one-third disc diameter in size at the fovea in the right
      eye. Fluorescein angiography demonstrated an irregular block of choroidal
      fluorescence corresponding to the yellowish lesion, which was surrounded by
      stellate retinal folds. Optical coherence tomography images showed a steep
      elevation of the retinal pigment epithelium (RPE) as a focally protruded
      reflective band over an optically clear space. Scanning laser ophthalmoscopy
      provided morphologic enhancement in the specifically affected layers of the
      macula. Using an argon green laser, band-shaped bright reflexes were seen in the
      right fovea. The helium-neon laser revealed a bright patch corresponding to the
      yellowish lesion over the fovea, which was surrounded by stellate retinal folds.
      The diode laser revealed a bright patch corresponding to the yellowish lesion.
      CONCLUSION: The stellate retinal folds of this patient were considered to be
      caused by the steep elevation of the RPE with an extracellular accumulation of
      the vitelliform deposits.

PMID- 11583680
TI  - 5-S-cysteinyldopa as diagnostic tumor marker for uveal malignant melanoma.
AB  - PURPOSE: To evaluate the clinical significance of 5-S-cysteinyldopa (5-S-CD), a
      major intermediate in melanin synthesis, as a potential diagnostic tumor marker
      for uveal malignant melanoma. METHODS: The levels of 5-S-CD in the serum were
      measured by high-performance liquid chromatography in 16 patients with primary
      uveal melanoma. The levels of 5-S-CD were also measured in both aqueous and
      vitreous humor in 10 patients with uveal melanoma. The serum of healthy
      volunteers and patients with skin diseases other than melanoma, and the
      intraocular fluids of patients with cataract and vitreoretinal diseases were used
      as controls. RESULTS: Serum concentrations of 5-S-CD in patients with uveal
      melanoma in the absence of extraocular metastases were close to those of
      controls; however, serum concentrations of 5-S-CD were significantly elevated in
      patients with extraocular metastases of melanoma. Concentrations of 5-S-CD in the
      intraocular fluids, especially vitreous humor, were higher in patients with uveal
      melanoma than in controls. CONCLUSIONS: 5-S-CD in intraocular fluids may serve as
      a useful biochemical marker for the diagnosis of uveal melanoma. Serum 5-S-CD may
      contribute to the assessment of the presence and progression of extraocular
      metastases in patients with uveal melanoma.

PMID- 11583681
TI  - Cataract surgery in patients with advanced Mooren's ulcer.
AB  - BACKGROUND: We describe 2 patients with severe Mooren's ulcer who underwent
      phacoemulsification and intraocular lens implantation surgery. The clinical
      features of this disease are highlighted. CASE: A detailed study of the ocular
      and laboratory findings in these patients, together with a review of the
      literature, is presented. OBSERVATIONS: There was a visually rewarding outcome
      after phacoemulsification and intraocular lens implantation were performed, and
      Mooren's ulcer did not recur. CONCLUSION: We conclude that phacoemulsification
      aspiration and intraocular lens implantation surgery with a small incision can be
      successfully performed in patients with Mooren's ulcer after complete control of
      inflammation with topical and oral steroid therapy, or with ocular reconstruction
      surgery when required.

PMID- 11583682
TI  - Cortical blindness following aortic arch surgery.
AB  - PURPOSE: To report a patient with Marfan's syndrome in whom cortical blindness
      occurred after planned circulatory arrest during aortic arch surgery. CASE: A 31
      year-old man underwent aortic arch surgery because of an acute aortic dissection
      due to Marfan's syndrome. He noticed poor vision after surgery, although his
      pupillary reflexes and fundi appeared normal. Magnetic resonance imaging (MRI)
      and positron emission tomography (PET) were performed 2 years and 9 months after
      his operation. RESULTS: The MRI revealed cortical atrophy in the occipital
      cortex, and PET scans with fluorodeoxy glucose revealed extreme glucose
      hypometabolism in the occipital cortex. The atrophy reflected cortical laminar
      necrosis that presumably occurred during the planned circulatory arrest to the
      brain during the surgery. CONCLUSION: It is occasionally difficult to diagnose
      cortical blindness with MRI, especially at the acute stage. We could find
      significant hypometabolism of the occipital cortex using PET.

PMID- 11583703
TI  - Particulate and vapor phase constituents of cigarette mainstream smoke and risk
      of myocardial infarction.
AB  - On pharmacological and compositional grounds, cigarette mainstream smoke (MS)
      aerosol can be broadly categorized as consisting of the following constituents:
      carbon monoxide, other vapor phase components, particulate matter ('tar') and
      nicotine. The relative risk of coronary artery disease for smoking 20 cigarettes
      per day has been estimated by meta-analysis of five large prospective
      epidemiology studies to be 1.78. These four major smoke components are
      simultaneously delivered to the active smoker as a complex aerosol composed of
      several billion semi-liquid particles per cm(3) within the mixture of combustion
      gases. Fractional attribution of the 78% increase in reported risk to a given
      constituent is problematic because of the complex mixture. However, a significant
      literature exists which suggests that some general statements regarding smoke
      constituent-associated risks for development or exacerbation of myocardial
      infarction are supportable. First, the atherogenic potential of MS is associated
      with the particulate and vapor phases and not with CO. Nicotine might exert an
      indirect effect on atherosclerotic plaque development by increasing shear forces
      in main conduction arteries. Similarly, the thrombogenic potential is associated
      primarily with the particulate and vapor phases and also possibly with nicotine
      via platelet aggregation. Vasoconstriction probably results from the actions of
      nicotine and hypoxia from carbon monoxide. Finally, the arrhythmia-inducing
      potential may result from catecholamine release following nicotine exposure, with
      a questionable contribution from carbon monoxide.

PMID- 11583704
TI  - Tetradecylthioacetic acid reduces stenosis development after balloon angioplasty
      injury of rabbit iliac arteries.
AB  - BACKGROUND: tetradecylthioacetic acid (TTA) is a synthetic long-chain fatty acid
      analogue that inhibits the oxidative modification of low-density lipoprotein
      particles in vitro. We examined the influence of TTA on the arterial wall
      response after balloon angioplasty injury in a rabbit iliac model. METHODS AND
      RESULTS: 14 rabbits were randomized to receiving either TTA fatty acids 800 mg
      daily perorally (weight 3.6+/-0.1 kg) or to normal diet (weight 3.5+/-0.5 kg,
      P=NS). Angioplasty was performed via right carotidotomy on both iliac arteries
      using an oversized balloon catheter, the TTA group being pretreated for 3 weeks.
      After angioplasty, the lumen diameter was 2.37+/-0.18 versus 2.36+/-0.13 mm for
      the TTA and control groups, respectively (P=NS). At 10 weeks follow-up
      angiography, minimal luminal diameter was 1.64+/-0.27 versus 1.13+/-0.52 mm for
      the TTA and control groups respectively (P<0.05). Histomorphometry did not show
      significant differences in intimal hyperplasia between the two groups (maximal
      intimal thickness 0.22+/-0.04 versus 0.19+/-0.10 mm, P=NS and intimal area 0.32+/
      0.12 versus 0.36+/-0.23 mm(2), P=NS for the TTA and the control groups,
      respectively). In the heart, the sum of the n-3 fatty acids was 8.9+/-2.7 in the
      TTA group versus 4.3+/-0.2 mol% in the control group (P<0.05). The anti
      inflammatory fatty acid index, calculated as (22:5 n-3+22:6 n-3+20:3 n-6)/20:4 n
      6, was 0.76+/-0.10 vs. 0.25+/-0.03 for the TTA and control groups, respectively
      (P<0.05). In vitro TTA (100 microM) reduced the proliferation of human smooth
      muscle cell by more than 50%. CONCLUSION: treatment with TTA is associated with
      positive arterial remodeling after angioplasty injury. The significance of the in
      vitro inhibition of human smooth muscle cell proliferation needs to be further
      elucidated.

PMID- 11583705
TI  - High-shear-stress-induced activation of platelets and microparticles enhances
      expression of cell adhesion molecules in THP-1 and endothelial cells.
AB  - Interaction between leukocyte and endothelial cells (ECs) is essential for
      vascular homeostasis and competent immune-inflammatory responses in vivo.
      Platelet-derived microparticles (PMPs) are generated by high shear stress and may
      appear in diseased small arteries and arterioles in various clinical settings. In
      this study, we used flow cytometry and confocal laser scanning microscopy to
      investigate the effects of high-shear-induced platelet and microparticle
      activation in adhesion molecules of THP-1 and ECs. We also measured the
      production of some cytokines and studied cytokine mRNA from THP-1 and ECs after
      PMP stimulation. PMP stimulation of THP-1 cells increased CD11b, CD32, and CD33
      but not CD29, CD31, and CD36. PMP stimulation of ECs increased CD54 and CD63 but
      not CD9, CD29, and CD31. PMPs induced interleukin-8 (IL-8), interleukin-1 beta
      (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) production by THP-1.
      PMPs also induced IL-8, IL-1 beta, and interleukin-6 (IL-6) production by ECs.
      Production was time-dependent. With RT-PCR, some cytokine mRNAs were detected in
      THP-1 and ECs after PMP stimulation. In relation to adhesiveness after PMP
      stimulation, we could clearly observe a shift in distribution not only of CD11b
      in THP-1 cells but also of CD54 in ECs. In addition, anti-P-selectin glycoprotein
      ligand-1 antibody reduced the expression of CD11b, CD32, and CD33 in THP-1 after
      PMP stimulation. These results suggest that high-shear-induced microparticles may
      contribute to the development of atherosclerosis and participate in vascular
      damage in inflammatory disorders.

PMID- 11583706
TI  - Ultrasonic tissue characterization of collagen in lipid-rich plaques in apoE
      deficient mice.
AB  - Mechanical failure of the fibrous cap of a vulnerable atherosclerotic plaque may
      lead to sudden plaque rupture and thus precipitate arterial thrombosis. Because
      ultrasound correlates strongly with mechanical features of tissues it might
      provide information on the stability of fibrous caps. The acoustic properties of
      the normal vessel wall and plaques, particularly fibrous caps of lipid-rich
      plaques, were evaluated in the aortic roots of six normal C57BL mice and 12
      atherosclerosis-prone apoE-deficient (apoE(-/-)) mice by scanning acoustic
      microscopy (SAM). After processing, the attenuation of high-frequency (1.1 GHz)
      focused ultrasound was measured in unstained tissue sections by SAM followed by
      quantification of the amount and type of collagen in picrosirius red stained
      sections by means of polarized light microscopy (PLM). The acoustic and optical
      images were superimposed and ultrasonic attenuation was measured in different
      tissue components. Pertinent plaque features, particularly fibrous caps covering
      lipid-rich pools, were clearly visualized by both SAM and PLM. Collagen appeared
      green in thin fibrous caps and bright orange in thick caps by PLM. The
      attenuation of ultrasound was significantly higher in the collagen fibers with
      orange color compared to those with green color (17.2 versus 6.6 x 10(3) dB/mm).
      SAM has shown the possibility to characterize the types of collagen by high
      frequency intravascular ultrasound in vivo and it might improve our understanding
      of the vulnerable plaque and its sudden rupture from micro-mechanical point of
      view.

PMID- 11583707
TI  - The effect of glucose and insulin on the activity of methylene tetrahydrofolate
      reductase and cystathionine-beta-synthase: studies in hepatocytes.
AB  - Hyperhomocysteinemia is a well established risk factor for cardiovascular
      disease, and multiple factors likely lead to abnormal regulation of plasma
      homocysteine in patients with diabetes. To examine a possible role for insulin
      and glucose in homocysteine metabolism, we examined the activity of two important
      enzymes of homocysteine metabolism in hepatocytes. In various tissues of six
      mice, methylene tetrahydrofolate reductase (MTHFR) activity was present in all
      tissues tested and the highest concentration (per gram) was in the brain. In
      contrast, cystathionine beta-synthase (CBS) activity appeared to be present only
      in the liver and to a small extent in the kidney. Using HEP G2 cells in culture,
      MTHFR activity was 3.3+/-0.8 nmol/h when the glucose concentration in the medium
      was 100 mg/dl and fell to 2.3+/-0.3 nmol/h when glucose was increased to 300
      mg/dl. MTHFR activity was 3.4+/-0.3 nmol/h when cells were exposed to an insulin
      concentration of 5 mU/ml and fell to 2.8+/-0.3 nmol/h when insulin concentration
      was increased to 200 mU/ml (P<0.01). In contrast CBS activity increased from
      0.017 to 0.13 U/ml by increasing the glucose concentration in the medium
      (P<0.01), but decreased from 0.04 to 0.02 (P<0.01) when the insulin concentration
      was increased from 5 to 200 mU/ml, respectively. We conclude that CBS and MTHFR
      have different tissue distributions, with CBS being present predominantly in
      liver and kidney, and MTHFR found in many tissues. In addition, both insulin and
      glucose affect the activity of the two enzymes when added to hepatocytes in
      vitro. If such effects occur in humans with hyperglycemia and hyperinsulinemia,
      then alterations in homocysteine metabolism may contribute to the accelerated
      macrovascular disease associated with insulin resistance or type 2 diabetes.

PMID- 11583708
TI  - Gene expression of apolipoprotein(a) within the wall of human aorta and carotid
      arteries.
AB  - Atherosclerosis is associated with arterial deposition of low density lipoprotein
      (LDL) and lipoprotein(a), Lp(a). Both lipoproteins have been detected in
      atherosclerotic vessels; however, while LDL has been shown to be only blood
      derived, it is not clear whether Lp(a) is also produced within the vessel wall.
      In the present investigation we studied gene expression of apo(a) and apoB in
      human blood vessels. Aorta, carotid arteries and liver specimens from 29 adult
      and pediatric autopsy cases were studied by RT-PCR and Southern blot analysis
      with primers and probes specific for apo(a), apoB and GAPDH (a control
      housekeeping gene). The mRNA of apo(a), but not apoB, was found within the vessel
      wall in both adult atherosclerotic arterial vessels and in pediatric non
      atherosclerotic vessels. Neither apo(a) nor apoB mRNA was detected in femoral
      veins. To verify the nature of the detected transcripts, we cloned the 162 base
      pair (bp) RT-PCR product derived from the arterial wall total RNA. Nucleotide
      sequencing revealed 100% homology with the apo(a) gene. Thus, while LDL in
      atherosclerotic arteries is exclusively blood-derived, the accumulation of Lp(a)
      within the artery may be due in part to in situ production of apo(a) within the
      vessel wall.

PMID- 11583709
TI  - VCAM-1 expression precedes macrophage infiltration into subendothelium of vein
      grafts interposed into carotid arteries in hypercholesterolemic rabbits--a
      potential role in vein graft atherosclerosis.
AB  - Intimal hyperplasia and atherosclerosis are major causes of late vein graft
      failure after coronary artery bypass surgery. Hypercholesterolemia appears to be
      a key risk factor for atherosclerosis in vein grafts as well as in native
      arteries. We used a rabbit model of interposition jugular vein graft to the
      carotid artery and compared intimal thickening, macrophage accumulation, and VCAM
      1 expression between hypercholesterolemic (H group) and normocholesterolemic (N
      group) rabbits. Fifty-nine rabbits were divided into H and N groups. Intimal
      thickening in vein grafts was approximately three times more prominent in the H
      group than in the N group. Macrophage accumulation progressively increased with
      time in H group vein grafts, although it was negligible in the N group. In the H
      group, moreover, macrophages were initially more abundant in deep intima, and
      subsequently accumulated in subendothelium of the grafted vein. VCAM-1 expression
      in luminal endothelial cells of the grafted veins was time-dependently increased
      after the vein graft surgery in both the H and N groups, and was more prominent
      in the H group. Comparison of the time-courses between macrophage accumulation
      and VCAM-1 expression revealed that VCAM-1 expression in luminal endothelium
      preceded subendothelial accumulation of macrophages. VCAM-1 expression and
      macrophage accumulation may be key factors which regulate progression of vein
      graft atherosclerosis.

PMID- 11583710
TI  - Hammerhead ribozyme targeting human platelet-derived growth factor A-chain mRNA
      inhibited the proliferation of human vascular smooth muscle cells.
AB  - Platelet-derived growth factor (PDGF) A-chain contributes to the pathogenesis of
      cardiovascular proliferative diseases, such as hypertensive vascular disease,
      atherosclerosis, and re-stenosis of an artery after angioplasty. To develop a
      ribozyme against human PDGF A-chain mRNA as a gene therapy for human arterial
      proliferative diseases, we designed and synthesized a 38-base hammerhead ribozyme
      to cleave human PDGF A-chain mRNA at the GUC sequence at nucleotide 591. In the
      presence of MgCl(2), synthetic hammerhead ribozyme to human PDGF A-chain mRNA
      cleaved the synthetic target RNA to two RNA fragments at a predicted size. Doses
      of 0.01-1.0 microM hammerhead ribozyme to human PDGF A-chain mRNA significantly
      inhibited angiotensin II (Ang II) and transforming growth factor (TGF)-beta(1)
      induced DNA synthesis in vascular smooth muscle cells (VSMC) from human in a dose
      dependent manner. One micromolor of hammerhead ribozyme to human PDGF A-chain
      mRNA significantly inhibited Ang II-induced PDGF A-chain mRNA and PDGF-AA protein
      expressions in VSMC from humans. These results indicate that the designed
      hammerhead ribozyme to human PDGF A-chain mRNA effectively inhibited growth of
      human VSMC by cleaving the PDGF A-chain mRNA and inhibiting the PDGF-AA protein
      expression in human VSMC. This suggests that the designed hammerhead ribozyme to
      PDGF A-chain mRNA is a feasible gene therapy for treating arterial proliferative
      diseases.

PMID- 11583711
TI  - Inhibition of the mitogen activated protein kinase, p38 alpha, prevents
      proinflammatory cytokine induction by human adherent mononuclear leukocytes in
      response to lipid loading.
AB  - Macrophage infiltration, inflammatory processes and oxidatively modified low
      density lipoprotein (LDL) are known contributing factors in the formation of the
      atherosclerotic plaque. To determine whether a direct link might exist between
      these factors, we examined the effect of oxidized LDL upon proinflammatory
      cytokine production in adherent human peripheral blood mononuclear leukocytes.
      Oxidized LDL, as well as a combination of cholesterol and 25-hydroxycholesterol,
      induced tumor necrosis factor-alpha (TNFalpha) and interleukin-1 beta (IL-1 beta)
      mRNA as measured by quantitative real time PCR, by a maximum of two- to fourfold
      following a 24-h incubation. Analysis of cell culture supernatants revealed a
      concomitant stimulation of TNFalpha and IL-1 beta secreted protein as determined
      by ELISA. Treatment of human peripheral blood mononuclear leukocytes with
      oxidized LDL or the combination of cholesterol and 25-hydroxycholesterol caused
      activation of p38 alpha as determined by the ability of immunoprecipitated p38 to
      phosphorylate an ATF-2 fusion protein, a surrogate substrate of p38 alpha. VK
      19911 (Pyridine, 4-[4-(4-fluorophenyl)-1-(4-piperidinyl)-1H-imidazol-5-yl]
      dihydrochloride), a specific inhibitor of p38 alpha, prevented the induction of
      TNFalpha and IL-1 beta by oxidized LDL in a dose-dependent manner. Activated p38
      alpha is known to be involved in the stabilization of cyclooxygenase-2 mRNA in
      response to stimuli such as lipopolysaccharide; however, in the setting of
      oxidized LDL-induced p38 alpha activation, COX-2 mRNA levels were not affected.
      Taken together, the data imply a potential role for p38 alpha activation in lipid
      associated inflammatory processes.

PMID- 11583713
TI  - Uptake of oxidized low-density lipoprotein in a THP-1 cell line lacking scavenger
      receptor A.
AB  - We previously isolated THP-1 subtype cells (sTHP-1), a cell line that expresses
      scanty amounts of scavenger receptor A (ScR-A) and does not undergo foam cell
      formation when incubated with acetylated low-density lipoprotein (Ac-LDL). In
      this study, we investigated the accumulation of esterified cholesterol in sTHP-1
      cells incubated with oxidized LDL (Ox-LDL), a physiologically modified
      lipoprotein in human. While sTHP-1 cells incubated with Ac-LDL accumulated only
      small amounts of esterified cholesterol, those incubated with Ox-LDL accumulated
      amounts similar to those accumulated by parent THP-1 (pTHP-1) cells. sTHP-1 cells
      expressed CD36 in amounts similar to the amounts expressed by pTHP-1 cells, and
      Ox-LDL was internalized through this CD36. The amount of accumulated esterified
      cholesterol was 73-81% of that accumulated in pTHP-1 cells expressing ScR-A. The
      levels of 125I-Ox-LDL binding, association, and degradation in sTHP-1 cells were
      64-70% of the corresponding levels in pTHP-1 cells. In our experiments utilizing
      ScR-A-deficient sTHP-1 cells and a specific antibody against human CD36, most of
      the Ox-LDL interacted with the CD36 receptor. In addition, a substantial amount
      of Ox-LDL (28-42%) was bound and degraded by sTHP-1 macrophages when both of the
      two major scavenger receptors, ScR-A and CD36, were deficient or blocked. These
      results indicate that CD36 in macrophages plays an important role in foam cell
      formation by Ox-LDL, while additional scavenger receptor(s) may take part in
      significant pathways of Ox-LDL uptake in macrophages.

PMID- 11583712
TI  - Identification of biochemical pathways for the metabolism of oxidized low-density
      lipoprotein derived aldehyde-4-hydroxy trans-2-nonenal in vascular smooth muscle
      cells.
AB  - Oxidation of low-density lipoproteins (LDL) generates high concentrations of
      unsaturated aldehydes, such as 4-hydroxy trans-2-nonenal (HNE). These aldehydes
      are mitogenic to vascular smooth muscle cells and sustain a vascular
      inflammation. Nevertheless, the processes that mediate and regulate the vascular
      metabolism of these aldehydes have not been examined. In this communication, we
      report the identification of the major metabolic pathways and products of [(3)H]
      HNE in rat aortic smooth muscle cells in culture. High-performance liquid
      chromatography separation of the radioactivity recovered from these cells
      revealed that a large (60-65%) proportion of the metabolism was linked to
      glutathione (GSH). Electrospray mass spectrometry showed that glutathionyl-1,4
      dihydroxynonene (GS-DHN) was the major metabolite of HNE in these cells. The
      formation of GS-DHN appears to be due aldose reductase (AR)-catalyzed reduction
      of glutathionyl 4-hydroxynonanal (GS-HNE), since inhibitors of AR (tolrestat or
      sorbinil) prevented GS-DHN formation, and increased the fraction of the
      glutathione conjugate remaining as GS-HNE. Gas chromatography-chemical ionization
      mass spectroscopy of the metabolites identified a subsidiary route of HNE
      metabolism leading to the formation of 4-hydroxynonanoic acid (HNA). Oxidation to
      HNA accounted for 25-30% of HNE metabolism. The formation of HNA was inhibited by
      cyanamide, indicating that the acid is derived from an aldehyde dehydrogenase
      (ALDH)-catalyzed pathway. The overall rate of HNE metabolism was insensitive to
      inhibition of AR or ALDH, although inhibition of HNA formation by cyanamide led
      to a corresponding increase in the fraction of HNE metabolized by the GSH-linked
      pathway, indicating that ALDH-catalyzed oxidation competes with glutathione
      conjugation. These metabolic pathways may be the key regulators of the vascular
      effects of HNE and oxidized LDL.

PMID- 11583715
TI  - Two polymorphisms in the apo A-IV gene and familial combined hyperlipidemia.
AB  - Linkage and association of the apo AI-CIII-IV gene region to familial combined
      hyperlipidemia (FCHL) was reported previously, based on the presence of genetic
      variants in the apo CIII and apo AI gene. No data were available yet on the
      contribution of the apo A-IV locus. Two DNA variants in exon 3 of the apo A-IV
      gene, A (Thr)(347)T (Ser) and [CTGT](3-4) were characterized by sequencing the
      coding region of the apo A-IV gene and were analyzed in our Dutch FCHL cohort (30
      probands, 159 affected relative, 317 unaffected relatives and 218 spouses). The
      genotype frequency of the A(347)T variant was different in probands and spouses.
      In probands no 2/2 carriers were found, resulting in a significant decreased
      frequency of the 2-allele (P<0.05). This was suggestive for a protective role of
      the presence of the serine (T) allele on the prevalence of FCHL. No difference in
      frequency distribution was found for the [CTGT](3-4) variant between the groups.
      Homozygous 4/4 carriers in spouses had a more favorable lipid profile (LDL
      cholesterol and apo B, P<0.05). The absence of linkage disequilibrium of the
      A(347)T with other markers in the gene cluster, and the absence of linkage
      disequilibrium with [CTGT](3-4) marker and the MspI-AI marker in the apo A-I
      promoter showed that these two apo A-IV variants reside on different haplotypes
      from the apo A-I and apo C-III markers. This was illustrated by extensive
      haplotype analysis. The present data on the contribution of DNA variants in the
      apo A-IV gene support our previous observations that the apo AI-CIII-AIV gene
      cluster has a complex genetic contribution to FCHL both by conferring
      susceptibility and protection.

PMID- 11583714
TI  - TCV-116 stimulates eNOS and caveolin-1 expression and improves coronary
      microvascular remodeling in normotensive and angiotensin II-induced hypertensive
      rats.
AB  - Angiotensin II (Ang II) plays an important role as a modulator of vascular
      structure and function in arterial hypertension. This study investigated the
      effects of an Ang II type 1 receptor antagonist, TCV-116, on endothelial nitric
      oxide synthase (eNOS) mRNA and protein expression, and NOS activity and eNOS
      regulatory protein caveolin-1 protein expression in the left ventricle of Wistar
      Kyoto rats treated for 2 weeks with Ang II (200 ng/kg/min) and evaluated these
      relations to myocardial remodeling. Rats given Ang II alone (ANGII) were compared
      with rats also receiving TCV-116 (ANGII-TCV). The eNOS mRNA and protein levels,
      and NOS activity and caveolin-1 protein expression in the left ventricle were
      significantly decreased in ANGII compared with control rats (CON), and were
      significantly increased in ANGII-TCV compared with ANGII. Moreover, compared with
      CON, the eNOS and caveolin-1 expression was significantly greater in CON treated
      with TCV-116. ANGII showed a significant increase of the wall-to-lumen ratio,
      perivascular and myocardial fibrosis, and type I collagen mRNA expression, with
      all these parameters being significantly improved by TCV-116. Thus, coronary
      microvascular and myocardial remodeling in normotensive and Ang II-induced
      hypertensive rats was significantly ameliorated by a subdepressor dose of TCV
      116, which may be at least in part mediated by an increase in local eNOS mRNA and
      protein expression, and NOS activity in the left ventricle.

PMID- 11583716
TI  - Histological and functional analysis of vascular smooth muscle cells in a novel
      culture system with honeycomb-like structure.
AB  - Vascular smooth muscle cells (SMCs) undergo phenotype change with the development
      of atherosclerosis. The phenotype changes of SMCs have been observed in various
      culture conditions, such as collagen-coated dishes. Here, we report the
      morphological and functional features of SMCs in a novel culture system using
      type I-collagen in a characteristic three-dimensional structure designated as
      honeycombs. The number of ribosome and mitochondria in SMCs cultured in
      honeycombs was one half or third of those cultured on collagen-coated plastic
      plates. DNA and protein synthesis of SMCs cultured in honeycombs were less than 1
      and 30-40%, respectively, of those cultured on plastic plates. In addition, PDGF
      BB did not increase the amount of DNA synthesis in SMCs in honeycombs. SMCs in
      honeycombs were shown to express several proteins, which are known to express in
      SMCs in medial layers of arteries. Particularly, caldesmon heavy chain was
      expressed in SMCs cultured in honeycombs, whereas not in those on plastic plates.
      Although focal adhesion kinase (FAK) was clearly detected in SMCs in honeycomb,
      the phosphotyrosine content of focal adhesion kin ase decreased in the process of
      culture. Immunoblot analysis showed dear different expression of ERK1 and ERK2 of
      mitogen-activated protein kinase in SMCs. SMCs in honeycombs expressed ERK2, more
      abundantly compared to ERK1, whereas SMCs in plates show the same levels of
      expressions for both proteins. Thus, the histological and functional feature of
      SMCs in the novel culture system is different from SMCs in plastic plates. The
      three-dimensional culture system described here may be indicating that cultured
      SMCs are able to express different proteins responding to the surrounding
      structures.

PMID- 11583717
TI  - A complex flow pattern of low shear stress and flow reversal promotes monocyte
      binding to endothelial cells.
AB  - Predilection sites for atherosclerosis within the vasculature are characterized
      by low shear stress and flow reversal. In this study, endothelial cells were
      exposed to a complex flow pattern that was characterized by particle velocity
      determination. Bovine aortic endothelial cells exposed to low shear stress and
      flow reversal demonstrated higher levels of monocyte binding compared to
      endothelial cells exposed to one-directional flow. In addition, endothelial cells
      exposed to low shear stress and flow reversal responded to inflammatory stimuli
      with substantial increases in monocyte binding, similar to that seen in cells
      exposed to one-directional flow. These findings suggest a mechanism by which
      areas of low shear stress and flow reversal are predisposed to the development of
      atherosclerotic lesions.

PMID- 11583718
TI  - Estrogen replacement therapy in postmenopausal women augments reactive hyperemia
      in the forearm by reducing angiotensin converting enzyme activity.
AB  - The precise mechanism of the vasoprotective effect of estrogen replacement
      therapy in postmenopausal women is not fully understood. The present study sought
      to determine the role of nitric oxide (NO) and angiotensin-converting enzyme
      (ACE) in the vasodilator response of the forearm vessels induced by estrogen
      administration to postmenopausal women. Subjects were divided into two groups.
      One group received conjugated equine estrogen (0.625 mg daily) orally for 3
      months (n=26), while the other received no treatment (control group, n=10).
      Forearm blood flow was measured by strain-gauge plethysmography. The
      concentrations of nitrite/nitrate (metabolites of NO), ACE activity, and lipid
      parameters were measured. Basal forearm blood flow, body weight, blood pressure,
      and heart rate were similar at baseline in both groups. After 3 months of
      estrogen administration, the maximal forearm blood flow response during reactive
      hyperemia and the serum level of nitrite/nitrate each showed a significant
      increase over baseline values: from 23.6+/-2.0 to 36.5+/-3.1 ml/min per 100 ml
      tissue (P<0.01), and from 24.8+/-2.3 to 38.6+/-3.6 micromol/l (P<0.01),
      respectively. Plasma levels of ACE activity were significantly reduced from
      baseline after 3 months of estrogen treatment (from 12.2+/-0.6 to 10.9+/-0.6
      IU/l, P<0.01). No changes were seen in controls. The change in forearm blood flow
      after sublingual nitroglycerin was similar at baseline versus after 3 months of
      estrogen administration. The increase in the serum level of nitrite/nitrate after
      3 months of estrogen therapy showed a significant inverse correlation (r=0.52,
      P<0.01) with the reduction in the plasma level of ACE activity. There was no
      significant correlation between the increase in serum nitrite/nitrate and any
      change in serum lipids, blood pressure, or other parameters. The administration
      of oral estrogen to postmenopausal women for 3 months increased the NO-mediated
      forearm endothelium-dependent vasodilatation. This was likely due, at least in
      part, to ACE inhibition. The latter may be one mechanism by which ERT provides
      its well-known cardiovascular benefit.

PMID- 11583719
TI  - Correlation of plasma homocysteine and mitochondrial DNA content in peripheral
      blood in healthy women.
AB  - Hyperhomocysteinemia is an independent risk factor of cardiovascular disease and
      associated with insulin resistance, although their causal relationship remains
      unclear. A previous report has shown that high concentration of homocysteine
      damages mitochondrial gene expression, function and structure. As we found
      recently, the mitochondrial DNA (mtDNA) contents are inversely correlated with
      insulin resistance parameters. Thus there is possibility that plasma total
      homocysteine (tHcy) level is somewhat correlated with mtDNA content. Sixty
      healthy women (mean age 40.3+/-20.9 yr, range 18-78 yr) were recruited to
      investigate the correlation of plasma tHcy level and mtDNA content in peripheral
      blood. A significant negative correlation was found between plasma tHcy levels
      and mtDNA content (r=-0.507, P<0.01). Plasma tHcy and mtDNA content have an
      independent effect on each other and on insulin resistance (HOMA-insulin
      resistance (IR) score) respectively in multiple regression model. Plasma tHcy
      showed positive correlations with age (r=0.407), W/H ratio (r=0.370), total
      cholesterol (r=0.338), LDL-cholesterol (r=0.317) and insulin resistance (HOMA-IR
      score) (r=0.261); and a negative correlation with folate (r=-0.273). MtDNA
      content showed negative correlations with age (r=-0.407), BMI (r=-0.440), W/H
      ratio (r=-0.659), SBP (r=-0.350), total cholesterol (r=-0.340), triglyceride (r=
      0.376), LDL-cholesterol (r=-0.349), fasting plasma insulin (r=-0.483), and
      insulin resistance (HOMA-IR score) (r=-0.423); and a positive correlation with
      folate (r=0.299). In this study, there was a significant inverse correlation
      between plasma tHcy level and mtDNA content. Further study will be warranted to
      elucidate the mechanism by which two factors are associated.

PMID- 11583720
TI  - Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL
      cholesterol additively.
AB  - Colesevelam hydrochloride is a novel, potent, non-absorbed lipid-lowering agent
      previously shown to reduce low density lipoprotein (LDL) cholesterol. To examine
      the efficacy and safety of coadministration of colesevelam and atorvastatin,
      administration of these agents alone or in combination was examined in a double
      blind study of 94 hypercholesterolemic men and women (baseline LDL cholesterol >
      or =160 mg/dl). After 4 weeks on the American Heart Association Step I diet,
      patients were randomized among five groups: placebo; colesevelam 3.8 g/day;
      atorvastatin 10 mg/day; coadminstered colesevelam 3.8 g/day plus atorvastatin 10
      mg/day; or atorvastatin 80 mg/day. Fasting lipids were measured at screening,
      baseline and 2 and 4 weeks of treatment. LDL cholesterol decreased by 12-53% in
      all active treatment groups (P<0.01). LDL cholesterol reductions with combination
      therapy (48%) were statistically superior to colesevelam (12%) or low-dose
      atorvastatin (38%) alone (P<0.01), but similar to those achieved with
      atorvastatin 80 mg/day (53%). Total cholesterol decreased 6-39% in all active
      treatment groups (P<0.05). High density lipoprotein cholesterol increased
      significantly for all groups including placebo (P<0.05). Triglycerides decreased
      in patients taking atorvastatin alone (P<0.05), but were unaffected by
      colesevelam alone or in combination. The frequency of side effects did not differ
      among groups. At recommended starting doses of each agent, coadministration of
      colesevelam and atorvastatin was well tolerated, efficacious and produced
      additive LDL cholesterol reductions comparable to those observed with the maximum
      atorvastatin dose.

PMID- 11583721
TI  - Changes in lipid metabolism and effect of simvastatin in renal transplant
      recipients induced by cyclosporine or tacrolimus.
AB  - Hyperlipidemia is frequently developed following renal transplantation and
      results in worsening of the patient's prognosis. In study 1, the effects of
      immunosuppressants, cyclosporine (CsA) and tacrolimus on serum lipids were
      compared in-patients undergoing renal transplantation. The study included 32
      cases of renal transplantation recipients who randomized to the CsA treatment
      group (15 patients) and the tacrolimus group (17 patients). Before and 1 month
      after the transplantation, we assessed the serum lipid levels, apolipoprotein
      levels, the concentrations of cholesterol in the respective lipoprotein fractions
      and the enzyme activities related to lipid-metabolism. The serum lipid levels in
      both groups were significantly increased at 1 month after renal transplantation.
      In the CsA group, there were significant increases in cholesterol contents in
      very-low-density lipoprotein (VLDL), LDL2 and HDL2 fractions, whereas, in the
      tacrolimus group, cholesterol content was increased in VLDL and HDL2 fractions.
      In study 2, 1 month after renal transplantation, 19 patients with
      hypercholesterolemia (total cholesterol (TC) >200 mg/dl) and hypertriglyceridemia
      (triglyceride (TG) >150 mg/dl) were treated with simvastatin 5-10 mg/day for 6
      months. Simvastatin treatment significantly decreased serum TC (240+/-29-200+/-22
      mg/dl, P<0.001), low-density lipoprotein cholesterol (LDL-C; 114+/-20-99+/-17
      mg/dl, P<0.05) and TG levels (217+/-103-130+/-38 mg/dl, P<0.01). In addition,
      there were significant decreases in very-low-density lipoprotein cholesterol
      (VLDL-C; 53+/-20-34+/-15 mg/dl, P<0.001). The Cmax and AUC of simvastatin were
      increased about eight-fold, when simvastatin was given in combination with CsA.
      In contrast, no significant changes in simvastatin levels were observed when
      combination with tacrolimus. Although simvastatin levels were increased with CsA,
      there were no abnormal changes in renal and liver functions, creatinine
      phosphokinase (CPK) levels or in incidence of adverse effects.

PMID- 11583722
TI  - Elevated levels of plasma homocyst(e)ine and asymmetric dimethylarginine in
      elderly patients with stroke.
AB  - Cerebrovascular risk factors, including hypertension, smoking, diabetes mellitus,
      aging, dyslipidemia, and hyperhomocyst(e)inemia are linked to endothelial
      dysfunction. Endothelial-derived nitric oxide (NO) has inhibitory effects on key
      processes in atherothrombosis. Although asymmetric dimethylarginine (ADMA), an
      endogenous inhibitor of NO synthase, is associated with atherosclerotic disease,
      there has been no report on association of ADMA with ischemic stroke. Here we
      investigated the relation of plasma ADMA, stroke, and homocyst(e)inemia in the
      elderly. Plasma ADMA and homocyst(e)ine concentration was determined using high
      performance liquid chromatography and fluorescence detection. Patients with
      ischemic stroke had significantly higher concentrations of plasma ADMA than
      controls (1.85+/-1.32 vs. 0.93+/-0.32 micromol/l, P=0.0001). After adjustment for
      risk factors, elevated ADMA levels, above 90th percentile of normal controls (>
      or =1.43 micromol/l) was associated with stroke (OR=6.05, 95% CI; 2.77-13.3,
      P=0.02). ADMA plasma levels were positively correlated to homocyst(e)ine levels
      (r=0.43, P=0.01). Multiple logistic regression analysis revealed that
      hyperhomocyst(e)inemia (plasma homocyst(e)ine concentration > or =15.0
      micromol/l) was a significant predictor of elevated ADMA level. Altogether,
      findings indicate that elevated ADMA concentrations are at increased risk for
      ischemic stroke in the elderly, and may account for increased risk of stroke in
      patients with hyperhomocyst(e)inemia.

PMID- 11583723
TI  - Correlations between peripheral differential leukocyte counts and carotid
      atherosclerosis in non-smokers.
AB  - Substantial evidence clearly indicates the immuno-inflammatory nature of
      atherosclerosis and the important roles of monocytes and other leukocytes in
      atherogenesis. The relationship between atherosclerosis and the peripheral
      monocyte count, however, has been equivocal and uncertain so far. One possible
      reason may be an opposing effect of different major risk factors of
      atherosclerosis on the monocyte count, e.g. smoking increases the monocyte count
      while hypercholesterolemia is accompanied by a lower monocyte count. Since
      smoking is well shown to increase leukocyte counts prominently in weeks, our
      study included only non-smokers who participated in a health check program at our
      hospital from 1996 to 1998 and had received a carotid duplex study with extra
      payment. Our results revealed the followings: In male non-smokers (n=571), the
      presence of carotid atherosclerosis was associated with significant increases in
      the counts of all leukocyte, neutrophil, and monocyte (P<0.005,<0.001 and <0.05,
      respectively), and, after adjustments for age and body mass index, there were
      significant positive links between these three leukocyte counts and the severity
      of carotid atherosclerosis, judged by either the sum score of all carotid plaques
      or the score of the most severe carotid plaque. On the contrary, in female non
      smokers (n=614), there was no significant link between differential leukocyte
      counts and either the presence or severity of carotid atherosclerosis. These
      results are compatible with recently recognized sex differences in the mechanism
      and pathophysiology of atherosclerosis, and together with relevant results in the
      literature, suggest that monocytes and neutrophils are the main types of
      leukocytes involved in atherosclerosis.

PMID- 11583724
TI  - The effect of hormone replacement therapy on serum homocysteine levels in
      perimenopausal women: a randomized controlled trial.
AB  - Serum homocysteine levels may be lowered by hormone replacement therapy, but
      randomized controlled trial data are scarce. We performed a single center
      randomized placebo-controlled trial to assess the 6 months effect of hormone
      replacement therapy compared with placebo on fasting serum homocysteine levels in
      121 perimenopausal women free of cardiovascular disease, and recruited from the
      general population. The trial was double-blind with respect to a sequential
      combined regimen of oral 17 beta-estradiol and desogestrel (17 beta E(2)-D) and
      the placebo group and open with respect to a combination of conjugated equine
      estrogens and norgestrel (CEE-N). At baseline and after 6 months, fasting serum
      homocysteine levels were measured. Differences in 6 months serum homocysteine
      levels from baseline between treatment and placebo groups were calculated, and
      expressed as a percentage of the 6 months placebo level. After 6 months, the
      difference in serum homocysteine levels between women receiving 17 beta E(2)-D
      and placebo was -6.3% (95% CI, -12.4%; 0.0%, P=0.06). The difference between
      women receiving CEE-N and placebo was -10.1% (95% CI, -16.7%; -2.9%, P<0.01). The
      difference between the combined group of both types of hormone replacement
      therapy users and placebo was -7.8% (95% CI, -13.2%; -2.0%, P=0.01). No
      significant difference was observed between the two active regimens. Our results
      indicate that hormone replacement therapy decreases homocysteine levels in
      perimenopausal women.

PMID- 11583725
TI  - The influence of plasma lipoprotein (a) on angiographic restenosis and coronary
      events in patients undergoing planned coronary balloon angioplasty. Ancillary
      analysis of the Fluvastatin Angioplasty Restenosis (FLARE) trial.
AB  - Elevated Lipoprotein (a) [Lp (a)] has been reported frequently, but not
      consistently, to be associated with restenosis following percutaneous
      transluminal coronary angioplasty (PTCA). The purpose of this study was to
      examine the association between Lp (a) and restenosis and clinical events in the
      context of a multi-centre randomised restenosis [Fluvastatin Angioplasty
      Restenosis (FLARE)] study of patients undergoing elective PTCA with full
      angiographic follow up. In the FLARE trial 40 mg fluvastatin twice daily did not
      influence restenosis, compared with placebo, after successful balloon
      angioplasty, measured as late loss in 834 patients, but did reduce the risk of
      death or myocardial infarction. Lp (a) was not effected by fluvastatin. Lp (a)
      and other biochemical details were established prior to planned PTCA. Among those
      undergoing successful PTCA, follow up angiography was performed at 26+/-2 weeks.
      Clinical follow up was complete to week 40. Included in this analysis are the 823
      patients who underwent successful angioplasty and had a baseline Lp (a) performed
      yielding 891 lesions for quantitative coronary angiography (QCA). No association
      was observed between Lp (a) and either quantitative markers of restenosis or
      binary restenosis rates. Late loss was 0.27 (SD 0.51) in the lowest quintile (Lp
      (a) 0-4 g/dl) compared with 0.23 (SD 0.49) (P>0.05). Elevated Lp (a) was not
      associated with an increased risk of individual or combined major coronary events
      over 40 weeks. A major adverse cardiac event (MACE) occurred in 41 (24%) of the
      lowest quintile and 42 (26%) of the highest (P>0.05). In conclusion, elevated Lp
      (a) was not associated with restenosis or clinical events following elective
      coronary balloon angioplasty in this randomised clinical trial and should not be
      considered a risk factor for post angioplasty restenosis.

PMID- 11583726
TI  - Fibrinogen is an antioxidant that protects beta-lipoproteins at physiological
      concentrations in a cell free system.
AB  - Oxidation of beta-lipoproteins has been linked to the development of
      arteriosclerosis. Using a copper mediated cell free system to oxidize beta
      lipoproteins, we found that beta -lipoproteins isolated from plasma were less
      susceptible to oxidation than lipoproteins from serum and that this was probably
      due to inhibition by fibrinogen, because removal of fibrinogen from plasma
      enhanced oxidation, while addition of fibrinogen restored inhibition. Fibrinogen
      inhibited conjugated diene formation and peroxide formation assayed by the
      xylenol orange assay (absorbance+/-confidence interval: 0.155+/-0.007 with
      fibrinogen vs 0.255+/-0.014 without) and retarded copper mediated oxidation of
      apolipoproteins in low density lipoproteins, reducing the distance of
      electrophoretic migration by 5 mm. The effect of fibrinogen was not due to
      chelation of copper, since it provided protection when hydrogen peroxide was
      substituted for copper as an oxidizing agent. At normal physiological
      concentration equivalents, fibrinogen showed superior antioxidant properties
      compared to albumin, melatonin, vitamin C and vitamin E and was superior to the
      vitamins when compared on an equimolar basis. Other studies have shown the
      fibrinogen to be more oxidizable than other major plasma proteins and to inhibit
      peroxide production. Because of its high mass concentration, we postulate
      fibrinogen is an important antioxidant protecting beta-lipoproteins in plasma and
      that it may be important in protecting lipoproteins in tissue spaces.

PMID- 11583727
TI  - Relationship between response of gamma-glutamyl transpeptidase to alcohol
      drinking and risk factors for coronary heart disease.
AB  - Alcohol drinking has been reported to influence the risk factors for coronary
      heart disease (CHD), such as the serum levels of triglycerides, HDL-cholesterol
      and uric acid, and the level of blood pressure. To examine whether there was
      individual variability in the response of these parameters to alcohol drinking, a
      cross-sectional study was conducted in 3130 men with a body-mass index (BMI)
      below 24. The subjects were divided into two groups; a normal gamma-glutamyl
      transpeptidase (rGTP) (<40 IU/l) group and a high rGTP (> or =40 IU/l) group, and
      the values were compared after adjusted for age, BMI, exercise and smoking. The
      level of triglycerides increased according to the amount of drinking in the high
      rGTP group, whereas no association was observed in the normal rGTP group. The
      level of HDL-cholesterol increased with drinking in the normal and high rGTP
      groups, and no difference was observed in the levels of HDL-cholesterol between
      the two groups. The levels of uric acid and blood pressure also increased with
      drinking in both groups, but the increase was bigger in the high rGTP group than
      in the normal rGTP group. The results indicated that there was large individual
      variability in the responses of the risk factors for coronary heart disease to
      drinking. Subjects whose rGTP responds less to drinking may have less
      disadvantageous effects of drinking.

PMID- 11583728
TI  - Differential lipogenic effects of cilostazol and pentoxifylline in patients with
      intermittent claudication: potential role for interleukin-6.
AB  - Cilostazol, a novel oral phosphodiesterase inhibitor, has shown consistent
      improvement in exercise tolerance in patients with intermittent claudication
      (IC). In addition to this effect, cilostazol has previously been shown to have
      beneficial effects on the dyslipidemia, i.e., combination of high triglycerides
      with low high-density-lipoprotein cholesterol (HDL-C) levels. Interleukin-6 (IL
      6) suppresses the activity of lipoprotein lipase, which modulates the metabolism
      of triglycerides and HDL-C. To determine whether a reduction of IL-6 contributes
      to the improvement of lipid profiles, we prospectively investigated the effect of
      cilostazol (n=16, 100 mg, twice daily) on the changes of lipid profiles and on
      the association with the changes of IL-6 compared with those of pentoxifylline
      (n=16, 400 mg, bid) in patients with IC. After eight weeks of administration of
      cilostazol to patients with IC, walking distances were increased, associated with
      a 29% decrease in plasma triglycerides and a 13% increase in HDL-C. No
      significant changes of lipid profiles in the pentoxifylline and placebo groups
      were observed although a similar improvement in walking distances was achieved in
      the pentoxifylline group. IL-6 levels were significantly reduced in patients
      receiving cilostazol as compared with those receiving placebo or pentoxifylline.
      The cilostazol-induced changes in the IL-6 were positively related to those of
      triglycerides in the cilostazol group (r=0.63, P<0.05) and negatively related to
      those of HDL-C (r=-0.55, P<0.05). These findings suggest that in addition to
      consistent improvement of exercise tolerance, cilostazol may improve lipid
      profiles by reducing IL-6 release. However, pentoxifylline did not affect lipid
      profiles although a similar improvement of maximal walking distance (MWD) was
      achieved.

PMID- 11583729
TI  - Increased leukocyte activity as a predictor for flow-limiting coronary lesions in
      patients with angina pectoris.
AB  - Myocardial ischemia initiates an acute inflammatory response, in which
      polymorphonuclear leukocytes (PMNs) are major participants. We investigated
      whether increased PMN activity in the peripheral blood is a marker for high-grade
      coronary artery stenosis in patients with angina pectoris. PMN activity was
      examined in 45 patients by measuring the luminol-dependent chemiluminescence (CL)
      response of the peripheral blood upon addition of phorbol myristate acetate
      (PMA). The CL of patients with angiographic filling delay was 1.6-fold higher
      than in patients without delay (480+/-54 vs. 302+/-33 counts/PMN, P<0.01). The CL
      of patients with a filling delay of the left anterior descending artery (LAD) was
      1.7-fold higher than in patients without an LAD filling delay (537+/-79 vs. 317+/
      27 counts/PMN, P<0.01). With the CL cut-off at 400 counts/PMN, the sensitivity
      and specificity for detecting an angiographic filling delay of the LAD were 69
      and 75%, respectively. These data indicate that PMN activity in the peripheral
      blood is increased with the presence of a flow-limiting coronary lesion showing
      an angiographic filling delay. Measuring PMN activity may be a useful approach to
      assess indications for and timing of angiography and/or adjunctive invasive
      therapies in patients with angina pectoris.

PMID- 11583730
TI  - Flow-mediated, endothelium-dependent vasodilatation is impaired in male body
      builders taking anabolic-androgenic steroids.
AB  - Self-administration of anabolic-androgenic steroids to increase muscular strength
      and lean body mass has been used widely among athletes. Flow mediated dilatation
      (FMD) determined by ultrasound of the brachial artery is accepted as both an in
      vivo index of endothelial function and an indicator for future atherosclerosis.
      FMD was calculated in 20 male non-smoking body builders in different phases of
      their training cycle and in six male non-smoking control athletes. Ultrasound
      studies of the brachial artery were performed according to the protocol of
      Celermajer et al. Of the entire training cycle, work-out phase was training phase
      without actual intake of anabolic-androgenic steroids over 8 weeks; build-up
      phase included actual intake of anabolic-androgenic steroids; and competition
      phase consisted of 8 weeks post intake of anabolic-androgenic steroids. Baseline
      characteristics did not differ between body builder groups except for a higher
      weight in competition phase body builders. Hormonal analysis revealed suppressed
      luteinizing hormone and follicle stimulating hormone levels in build-up phase
      body builders. The lipid profiles showed a marked reduction of HDL-C in build-up
      phase body builders. FMD was reduced in body builders of all phases when compared
      to control athletes (work-out phase: 2.5+/-2.7%; build-up phase: 2.1+/-3.0%;
      competition phase: 0.4+/-2.9% vs. 10.9+/-4.4%, P<0.05 by pairwise comparison
      using Scheffe's test for work-out phase, build-up phase and competition phase vs.
      control athletes). The glyceryl trinitrate-induced vasodilatation was diminished,
      though not statistically significantly, in body builders when compared with
      control athletes. The differences in FMD persisted after adjustment for vessel
      size. Our data indicate that intake of anabolic-androgenic steroids is associated
      with both an atherogenic blood lipid profile and endothelial dysfunction and thus
      may pose an increased risk of atherosclerosis.

PMID- 11583732
TI  - C-reactive protein and other markers of inflammation among patients undergoing
      HELP LDL apheresis.
AB  - Studies reveal important prognostic relationships between C-reactive protein
      (CRP) and atherosclerotic complications. A prospective trial of familial
      hypercholesterolemic patients treated with Heparin-induced Extra-corporeal Low
      Density Lipoprotein Precipitation (HELP, B. Braun Melsungen) therapy was
      undertaken to evaluate the short- and long-term effects on CRP. Four patients
      received LDL apheresis therapy on an alternate week basis for 6 months. Pre- and
      post-treatment serum high sensitivity (hs) CRP levels (IMx(R), Abbott
      Laboratories), LDL-C, triglycerides, and fibrinogen were measured. Pre- and post
      treatment mean serum levels of LDL-C were 281+/-76 and 98+/-34 mg/dl;
      triglycerides 191+/-64 and 123+/-50 mg/dl; fibrinogen 332+/-46 and 117+/-31
      mg/dl, respectively. Before and after apheresis mean serum levels of hsCRP were
      8.99+/-7.88 and 3.15+/-3.16 mg/ml, respectively, representing a 65% decrease.
      After 6 months of therapy, pre-treatment hsCRP showed an overall mean level
      decrease of 49%. Preliminary results indicate that LDL apheresis results in a
      rapid and long-term decrease of serum hsCRP levels.

PMID- 11583731
TI  - Transient increase of monocyte adhesion after a single dose of simvastatin.
AB  - Beneficial effects of HMG-CoA reductase inhibitors, such as simvastatin have been
      attributed to lipid lowering and cholesterol-independent mechanisms, for example
      a reduction of monocyte adhesion to endothelium. However, little is known about
      acute effects of statin intake. In an attempt to test for short-term effects of
      drug intake, we found that the adhesion of blood monocytes isolated from healthy
      volunteers or mildly hypercholesterolemic patients was increased after intake of
      simvastatin but not placebo at 0.5 h and declined to baseline levels at 3 h.
      Blood cholesterol levels were unaltered and the observed effects did not
      correlate with systemic concentrations of the pro-drug nor the active drug
      concentration in the peripheral circulation. In conclusion, the transient
      increase in adhesiveness of monocytes may be due to direct and/or enterohepatic
      metabolites of simvastatin, demonstrating the necessity of drug metabolism for
      exerting the beneficial effects of long-term treatment.

PMID- 11583733
TI  - Activity and antigen levels of thrombin-activatable fibrinolysis inhibitor in
      plasma of patients with disseminated intravascular coagulation.
AB  - We measured the plasma levels of thrombin-activatable fibrinolysis inhibitor
      (TAFI) activity and antigen in patients with disseminated intravascular
      coagulation (DIC) to examine the relationship between hypofibrinolysis and the
      pathogenesis of DIC. TAFI activity and antigen levels in the plasma were both
      significantly low in patients with DIC. TAFI activity in plasma was correlated
      with TAFI antigen, indicating that activity and antigen correspond well. The
      decrease of TAFI activity in DIC may be due to enhanced consumption. Since the
      plasma thrombin-antithrombin III complex (TAT) level was found to be elevated in
      DIC, increase of thrombomodulin-thrombin complex generation is suggested in this
      state. TAFI activity and antigen levels were negatively correlated with TAT and D
      dimer, suggesting that the plasma levels of TAFI are reduced by thrombin
      generation. Since TAFI was not correlated with fibrinogen, plasma-alpha(2)plasmin
      inhibitor complex (PPIC) and tissue type plasminogen activator/plasminogen
      activator inhibitor-1 (tPA/PAI-1) complex, TAFI might be a secondary modulator of
      fibrinolysis. The TAFI activity in plasma was significantly low in patients with
      infection and in those with organ failure, suggesting that TAFI may play an
      important role in the mechanism of organ failure in DIC-associated sepsis. In
      brief, TAFI may play an important role in the pathogenesis of DIC and organ
      failure.

PMID- 11583734
TI  - Sleeve-related thrombosis: a new form of catheter-related thrombosis.
AB  - In a detailed study of central venous catheter-related sleeve and thrombosis in
      experimental animals, a new form of thrombosis was detected and termed sleeve
      related thrombosis. A silastic catheter was placed in the jugular vein and the
      anterior vena cava of 22 rabbits and 54 rats. After intervals of 1, 3, 7 days, 2,
      3, 4 weeks and 1, 2, 4, 6 months the veins were examined by light microscopy and
      by transmission electron microscopy. In about 50% of the rats a thrombus was
      observed at the end of the catheter sleeve. Consecutive cutting allowed the
      visualization of a transition from a sleeve via part of sleeve and part of
      thrombus to a pure thrombus. This thrombus was separated from the vein wall and
      could not be considered a mural thrombus. As the thrombus was only attached to
      the terminal part of the organized catheter sleeve we propose the name sleeve
      related thrombosis.

PMID- 11583735
TI  - Specific inhibiting characteristics of tetramethylpyrazine, one of the active
      ingredients of the Chinese herbal medicine 'Chuanxiong,' on platelet thrombus
      formation under high shear rates.
AB  - We have investigated the effects of tetramethylpyrazine, one of the active
      ingredients of the Chinese herbal medicine Chuanxiong, on platelet thrombus
      formation under flow conditions. We demonstrate herein that tetramethylpyrazine
      inhibits shear-induced platelet aggregation under relatively high shear rate of
      10,800 s(-1) with modest inhibition of those occurring under relatively low shear
      rate of 1200 s(-1) by using optically modified cone-plate viscometer. We also
      demonstrate that platelet activation induced by shearing in the absence of
      exogenous platelet-activating agents such as ADP as evidenced by P-selectin
      surface expression and microparticle release detected by quantitative flow
      cytometry was also inhibited by tetramethylpyrazine. Moreover, we also
      demonstrate platelet thrombus formation on the collagen and von Willebrand factor
      (vWF) surface at high shear rates without significant influences on those
      occurring under relatively low shear rates. Because platelet thrombus formation
      occurring under high shear rates is known to be mediated by the vWF interaction
      with platelet receptor proteins GP Ibalpha and GP IIb/IIIa, we speculated that
      tetramethylpyrazine exerts antiplatelet effects by inhibiting the vWF-mediated
      process of platelet thrombus formation. Our findings, indicating the unique
      antiplatelet characteristics of tetramethylpyrazine, selectively inhibiting the
      platelet thrombus formation under high shear rates, provide good reasons for
      developing chemical analogs having biological functions similar to or more potent
      than those of tetramethylpyrazine as antiplatelet agents having unique biological
      functions.

PMID- 11583736
TI  - Cyclic nucleotides in platelets of genetically hypertriglyceridemic and
      hypertensive rats. Thrombin and nitric oxide responses are unrelated to plasma
      triglyceride levels.
AB  - Prague hereditary hypertriglyceridemic (HTG) rats constitute a genetic model of
      hypertension associated with hyperlipidemia and insulin resistance. Various cell
      alterations, including changes in membrane dynamics, ion transport, and decreased
      platelet responses to thrombin have been observed in this strain. As
      hypertriglyceridemia appears to be associated with reduced endothelium-dependent
      vasodilation and platelet aggregation, we examined whether triglycerides could
      modulate cell responsiveness through changes in cyclic nucleotides in platelets
      of HTG rats. From the age of 6 weeks, these hypertensive animals were subjected
      for 10 weeks to interventions that modified circulating triglycerides levels
      (2.17+/-0.09 mmol/l), leading to their reduction (gemfibrozil treatment, 0.87+/
      0.05 mmol/l) or elevation (high fructose intake, 3.23+/-0.07 mmol/l). Basal
      cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)
      contents were 15% and 48% lower in isolated platelets of HTG rats than in those
      of Lewis controls. cAMP level was further reduced in HTG rats subjected to high
      fructose intake. Irrespective of their plasma triglyceride levels, the thrombin
      induced increase in platelet cGMP levels present in Lewis rats was absent in
      platelets of HTG rats. In contrast, no strain- or treatment-related differences
      were observed in the magnitude or kinetics of cGMP response to exogenous nitric
      oxide (NO). NO-induced cGMP and cAMP changes were associated in an opposite
      manner with trimethylamino-diphenylhexatriene (TMA-DPH) anisotropy, a biophysical
      parameter that reflects the microviscosity of the outer part of the cell
      membrane. Our results indicate that the attenuation of platelet responsiveness to
      thrombin in HTG rats represents a strain difference that cannot merely be due to
      a difference in plasma triglyceride levels. Platelet hyporesponsiveness to
      agonists such as thrombin in HTG rats cannot be explained by a change in levels
      of inhibitory cyclic nucleotides, since they were actually found to be low and
      not high.

PMID- 11583737
TI  - Reactivity of human platelets with immobilized fibrinogen is dictated by the
      chemical character of the surface.
AB  - Quiescent platelets readily adhere to surface-immobilized fibrinogen. In
      contrast, platelets exposed to soluble fibrinogen do not demonstrate such
      activity. As part of an effort to characterize this phenomenon, a solid-phase
      reagent was prepared by adsorbing human fibrinogen to polystyrene-divinylbenzene
      microparticles. Using a suspension of human platelets, phase-contrast microscopy
      was used to quantitate directly platelets bound to fibrinogen-coated beads. This
      method is fast, straightforward, and requires minimal amounts of reagents and
      sample. An existing turbidimetric assay was modified to monitor optically the
      rate and extent of platelet-fibrinogen binding. When platelet-rich plasma was
      added to a stirred suspension of fibrinogen-coated beads, the rate of aggregation
      was related directly to the concentration of fibrinogen on the bead surface. This
      response could not be mitigated by the thrombin inhibitor, hirudin, indicating
      that any thrombin generated in the reaction has no role in bead aggregation.
      Conversely, the alpha(IIb)beta(3) antagonist, abciximab (ReoPro), completely
      prevented aggregation, implicating specific fibrinogen-alpha(IIb)beta(3)
      interactions as responsible for the observed effect. Beads coated with either
      albumin or a densely packed, pure film of the neutral phospholipid,
      phosphatidylcholine (lecithin), do not aggregate under identical conditions, nor
      do fibrinogen-coated beads aggregate when platelet-depleted plasma is added. When
      fibrinogen was coated to beads as a mixed film with lecithin, a striking increase
      in reactivity toward platelets was demonstrated, compared to unmodified beads.
      These studies indicate that the observed adhesion of platelets to beads is a
      direct result of platelet-fibrinogen interactions and platelets respond
      differently to fibrinogen when presented as a mixed film with lipid, compared to
      the protein alone at an interface.

PMID- 11583738
TI  - Comparison of the effect of different platelet GPIIb/IIa antagonists on the
      dynamics of platelet/fibrin-mediated clot strength induced using
      thromboelastography.
AB  - The effect of various platelet glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists on
      the dynamics of platelet-fibrin clot formation and strength induced by various
      stimuli was measured by thromboelastography (TEG). GPIIb/IIIa antagonists with
      high affinity for resting and activated platelets and with slow rates of
      dissociation from GPIIb/IIIa (Class I antagonists) demonstrated potent and
      comparable inhibition of platelet aggregation and tissue factor (TF),
      lipopolysaccharide (LPS), Factor Xa, and thrombin-induced clot strength, in
      contrast to antagonists that dissociate rapidly from GPIIb/IIIa (Class II
      antagonists). For example, the Class I antagonist XV459 (the free acid form of
      roxifiban) inhibited TF, endotoxin, Factor Xa, and thrombin-induced maximal clot
      strength and platelet aggregation with an IC(50)=30-70 nM, whereas the IC(50) of
      the Class II antagonist YZ211 (the free acid form of sibrafiban) for altering
      clot formation and strength was 0.3-4.7 microM. Moreover, the IC(50)'s of
      sibrafiban, and another Class II antagonist, orbofiban, for inhibiting platelet
      fibrin clot formation and strength were substantially greater than their
      clinically achievable concentrations. Further, although aspirin treatment
      improved the efficacy of all GPIIb/IIIa antagonists, it did not alter the
      differences between Classes I and II antagonists. Thus, these data indicate that
      there are differences in the efficacy of various GPIIb/IIIa antagonists in
      inhibiting platelet-fibrin clot formation and strength. They also suggest that
      inhibiting platelet aggregation may not be the sole determinant for the in vivo
      efficacy of various GPIIb/IIIa antagonists.

PMID- 11583739
TI  - Evaluation of the xylum clot signature analyzer in normal subjects and patients
      with the Hermansky-Pudlak syndrome.

PMID- 11583740
TI  - The trimannosyl cores of N-glycans are important for the procoagulant protease
      inhibitory activity of urinary protein C inhibitor.
AB  - We investigated the relationship between the procoagulant protease-inhibitory
      activity and the N-glycan structures in urinary protein C inhibitor (uPCI) by
      sequential exoglycosidase digestions based on the N-glycan structures elucidated
      in this report. uPCI was glycosylated on the three potential N-glycosylation
      sites, asparagines 230, 243 and 319 (N230, N243 and N319) in the molecule and had
      four biantennary complex type sugar chains. The inhibitory activities of uPCI
      toward thrombin and plasma kallikrein were little changed by the sequential
      removal of N-acetylneuraminic acid and galactose residues from the termini and N
      acetylglucosamine residues from the branches of the N-glycans. However, the
      inhibitory activities were markedly decreased by further removing alpha-mannose
      residues from the trimannosyl cores of the N-glycans. These results suggest that
      the trimannosyl cores of N-glycans are important for uPCI to inhibit the
      procoagulant protease.

PMID- 11583741
TI  - A world war against terrorism.

PMID- 11583742
TI  - Approach to symptomatic coronary disease in the elderly: TIME to change?

PMID- 11583743
TI  - Role of inflammatory biomarkers in prediction of coronary heart disease.

PMID- 11583744
TI  - Back to nephrectomy for patients with metastatic renal cancer.

PMID- 11583745
TI  - New developments in impulsivity.

PMID- 11583746
TI  - Health economics without tears.

PMID- 11583747
TI  - Trial of invasive versus medical therapy in elderly patients with chronic
      symptomatic coronary-artery disease (TIME): a randomised trial.
AB  - BACKGROUND: Since previous randomised treatment trials in coronary disease have
      focused on patients younger than 75 years of age, their findings might not apply
      to the elderly population in whom the cardiac risk profile, risk of intervention,
      and comorbidities are increased. We aimed to assess quality of life and outcome
      of elderly patients with coronary disease after medical or revascularisation
      therapy. METHODS: In this randomised, prospective, multicentre trial, we enrolled
      patients aged 75 years or older with chronic angina of at least Canadian Cardiac
      Society class II despite at least two antianginal drugs. Patients were randomly
      assigned coronary angiography and revascularisation or optimised medical therapy.
      The primary endpoint was quality of life after 6 months, as assessed by
      questionnaire and the presence of major adverse cardiac events (death, non-fatal
      myocardial infarction, or hospital admission for acute coronary syndrome with or
      without the need for revascularisation). Analysis was by intention to treat.
      FINDINGS: 150 patients were assigned medical therapy and 155 invasive therapy.
      Two protocol violators in each group were not included in the analysis. After 6
      months, angina severity decreased and measures of quality of life increased in
      both treatment groups; however, these improvements were significantly greater
      after revascularisation. Major adverse cardiac events occurred in 72 (49%) of
      patients in the medical group and 29 (19%) in the invasive group (p<0.0001).
      INTERPRETATION: Patients aged 75 years or older with angina despite standard drug
      therapy benefit more from revascularisation than from optimised medical therapy
      in terms of symptom relief and quality of life. Therefore, these patients should
      be offered invasive assessment despite their high risk profile followed by
      revascularisation if feasible.

PMID- 11583749
TI  - Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus
      ribavirin for initial treatment of chronic hepatitis C: a randomised trial.
AB  - BACKGROUND: A sustained virological response (SVR) rate of 41% has been achieved
      with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this
      randomised trial, peginterferon alfa-2b plus ribavirin was compared with
      interferon alfa-2b plus ribavirin. METHODS: 1530 patients with chronic hepatitis
      C were assigned interferon alfa-2b (3 MU subcutaneously three times per week)
      plus ribavirin 1000-1200 mg/day orally, peginterferon alfa-2b 1.5 microg/kg each
      week plus 800 mg/day ribavirin, or peginterferon alfa-2b 1.5 microg/kg per week
      for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000-1200 mg/day for 48
      weeks. The primary endpoint was the SVR rate (undetectable hepatitis C virus
      [HCV] RNA in serum at 24-week follow-up). Analyses were based on patients who
      received at least one dose of study medication. FINDINGS: The SVR rate was
      significantly higher (p=0.01 for both comparisons) in the higher-dose
      peginterferon group (274/511 [54%]) than in the lower-dose peginterferon (244/514
      [47%]) or interferon (235/505 [47%]) groups. Among patients with HCV genotype 1
      infection, the corresponding SVR rates were 42% (145/348), 34% (118/349), and 33%
      (114/343). The rate for patients with genotype 2 and 3 infections was about 80%
      for all treatment groups. Secondary analyses identified bodyweight as an
      important predictor of SVR, prompting comparison of the interferon regimens after
      adjusting ribavirin for bodyweight (mg/kg). Side-effect profiles were similar
      between the treatment groups. INTERPRETATION: In patients with chronic hepatitis
      C, the most effective therapy is the combination of peginterferon alfa-2b 1.5
      microg/kg per week plus ribavirin. The benefit is mostly achieved in patients
      with HCV genotype 1 infections.

PMID- 11583750
TI  - Radical nephrectomy plus interferon-alfa-based immunotherapy compared with
      interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial.
AB  - BACKGROUND: Surgery is the main treatment for localised renal cell carcinoma, but
      use of radical nephrectomy for metastatic disease is highly controversial. We
      aimed to establish whether radical nephrectomy done before interferon-alfa-based
      immunotherapy improved time to progression and overall survival (primary
      endpoints) compared with interferon alfa alone. METHODS: We included 85 patients
      from June, 1995, to July, 1998: two (one per group) were ineligible. 42 of the 83
      participants were randomly assigned combined treatment (study group) and 43
      immunotherapy alone (controls). All patients had metastatic renal-cell carcinoma
      that had been histologically confirmed and was progressive at entry. In study
      patients, surgery was done within 4 weeks of randomisation, and immunotherapy
      (5x10(6) IU/m(2) subcutaneously three times per week) started 2-4 weeks later. In
      controls, immunotherapy was started within 1 working day of randomisation. Follow
      up visits were monthly. All analyses were by intention to treat. FINDINGS: 40
      (53%) of 75 patients received at least 16 weeks of interferon-alfa treatment,
      which was also the median duration of treatment. Time to progression (5 vs 3
      months, hazard ratio 0.60, 95% CI 0.36-0.97) and median duration of survival were
      significantly better in study patients than in controls (17 vs 7 months, 0.54,
      0.31-0.94). Five patients responded completely to combined treatment, and one to
      interferon alfa alone. Dose modification was necessary in 32% of patients, most
      commonly because of non-haematological side-effects. INTERPRETATION: Radical
      nephrectomy before interferon-based immunotherapy might substantially delay time
      to progression and improve survival of patients with metastatic renal cell
      carcinoma who present with good performance status.

PMID- 11583751
TI  - Soluble adhesion molecules and prediction of coronary heart disease: a
      prospective study and meta-analysis.
AB  - BACKGROUND: Previous studies have suggested that circulating concentrations of
      soluble adhesion molecules are useful predictors of risk of coronary heart
      disease (CHD). Larger studies are needed, however, to test this hypothesis.
      METHODS: We measured serum concentrations of four soluble cell adhesion molecules
      (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1
      [VCAM-1], E-selectin, and P-selectin) in the stored baseline serum samples of 643
      men with coronary heart disease and 1278 controls nested in a prospective sutdy
      of 5661 men who were monitored for 16 years. We also did a meta-analysis of
      previous relevant studies to place our findings in context. RESULTS:
      Concentrations of soluble adhesion molecules were significantly associated with
      one another, with other markers of inflammation, and with some classic coronary
      risk factors. For ICAM-1, the odds ratio for CHD was 1.68 (95% CI 1.32-2.14) in a
      comparison of men in the top third with those in the bottom third of baseline
      measurements after adjustments for age and town. This decreased to 1.11 (0.75
      1.64) after adjustment for some classic coronary risk factors and indicators of
      socioeconomic status. For the three other cell adhesion molecules, the odds
      ratios for CHD, first adjusted for age and town only, and then additionally
      adjusted for other risk factors, were: VCAM-1: 1.26 (0.99-1.61) and 0.96 (0.66
      1.40); E-selectin: 1.27 (1.00-1.61) and 1.13 (0.78-1.62); and P-selectin: 1.23
      (0.96-1.56) and 1.20 (0.81-1.76). INTERPRETATION: The measurement of these
      adhesion molecules is unlikely to add much predictive information to that
      provided by more established risk factors.

PMID- 11583753
TI  - A fish bone in the liver.

PMID- 11583752
TI  - Guided self-management and patient-directed follow-up of ulcerative colitis: a
      randomised trial.
AB  - BACKGROUND: Ulcerative colitis is managed mainly in secondary care by regular
      outpatient reviews done by specialist clinicians. Alternatives would be to
      discharge patients to primary care or to provide open-access clinics, but neither
      of these options reduce patients' dependency on doctors or allow patients'
      involvement in disease management. We did a randomised controlled trial to assess
      an alternative to traditional outpatient care. METHODS: We randomly assigned 203
      patients with ulcerative colitis who were undergoing hospital follow-up to
      receive patient-centred self-management training and follow-up on request
      (intervention group), or normal treatment and follow-up (control group). The main
      outcome was the interval between relapse and treatment, and secondary outcomes
      were rates of primary and secondary care consultation, quality of life, and
      acceptability to patients. Analysis was by intention to treat. FINDINGS:
      Intervention patients had relapses treated within a mean of 14.8 h (SD 19.1)
      compared with 49.6 h (65.1) in controls (difference 34.8 h [95% CI 16.4-60.2]).
      Furthermore, intervention patients compared with controls made significantly
      fewer visits to hospital (0.9 vs 2.9 per patient per year, difference 2.0 [1.6
      2.7]) and to the primary-care physician (0.3 vs 0.9 per patient per year,
      difference 0.6 [0.2-1.1], p<0.006). Only two patients in the intervention group
      preferred traditional management. Health-related quality-of-life scores were
      unchanged in both groups. INTERPRETATION: Self-management of ulcerative colitis
      accelerates treatment provision and reduces doctor visits, and does not increase
      morbidity. This approach could be used in long-term management of many other
      chronic diseases to improve health-service provision and use, and to reduce
      costs.

PMID- 11583754
TI  - Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in
      patients with cystic fibrosis.
AB  - Early antibiotic treatment of airway colonisation with Pseudomonas aeruginosa can
      delay onset of chronic lung infection in patients with cystic fibrosis. Whether
      the pathogen is eradicated by this treatment is unclear. We successfully
      eradicated the organism in 14 of 15 patients with cystic fibrosis who had been
      colonised by P aeruginosa. Patients inhaled 80 mg tobramycin twice daily for 12
      months. Eradication was confirmed by sequential respiratory cultures and serum
      antibody titres that were negative for P aeruginosa. Our antibiotic therapy
      regimen maintained pulmonary function at high levels.

PMID- 11583755
TI  - MHC class II region, CTLA4 gene, and ophthalmopathy in patients with Graves'
      disease.
AB  - Up to half of patients with Graves' hyperthyroidism have signs of thyroid
      associated ophthalmopathy, but the factors that cause this disorder are unknown.
      We investigated two major genetic susceptibility loci for Graves' disease in
      ophthalmopathy; the MHC class II region and the cytotoxic T lymphocyte antigen-4
      (CTLA4) gene. Allelic frequencies of these genes in patients with Graves' disease
      who did and did not have concurrent thyroid-associated ophthalmopathy did not
      differ, and are, therefore, unlikely to contribute to its development.

PMID- 11583756
TI  - Breastfeeding: it is worth trying with the second baby.
AB  - Mothers who experience breastfeeding difficulties with their first babies and
      give up breastfeeding are less likely to breastfeed subsequent babies than
      mothers who do not experience such difficulties. We carried out a longitudinal
      study of 22 mothers in which milk output was measured at 1 week and 4 weeks after
      giving birth to their first and second babies. Significantly more breast milk was
      produced at 1 week for the second lactation (an increase of 31% [95% CI 11-51%])
      and the net increase was greatest for those with the lowest milk output on the
      first occasion (90% [30-149%]). They spent less time feeding their second baby (a
      decrease of 20% [-34 to -5%]). This increased efficiency of milk transfer was
      also evident at 4 weeks. Health professionals should encourage women to
      breastfeed all their children, whatever their experience with their first child.

PMID- 11583757
TI  - Non-invasive distension of the small bowel for magnetic-resonance imaging.
AB  - Magnetic resonance enteroclysis is a promising technique that allows assessment
      of the small bowel but needs invasive nasoduodenal intubation. We propose a non
      invasive distension method for magnetic-resonance imaging (MRI) in which
      ispaghula, dissolved in an aqueous solution with meglumine gadoterate taken
      orally over 4 h forms a viscous hydrogel within the intestinal lumen. MRI results
      from ten volunteers showed good luminal distension, constant signal homogeneity,
      optimum demarcation of the bowel content from surrounding tissues, and a low rate
      of artefacts. Our method permits non-invasive high quality MRI of the small
      bowel.

PMID- 11583758
TI  - A new prognostic tool on the horizon for breast cancer?

PMID- 11583759
TI  - Some evidence cognitive therapy and exercise benefit chronic fatigue.

PMID- 11583760
TI  - Gene removes muscular dystrophy symptoms in mouse model.

PMID- 11583764
TI  - Bovine spongiform encephalopathy case found in Japan.

PMID- 11583765
TI  - Peer-review meeting participants urge greater accountability.

PMID- 11583766
TI  - Ireland's doctors' leaders offer subtle shift on abortion stance.

PMID- 11583767
TI  - Research halted at Indian centre accused of misconduct.

PMID- 11583768
TI  - Introduction to health economics for physicians.
AB  - Since the 1960s, expenditure on health care in developed countries has risen
      faster than the general rate of inflation, thus making economic assessment of
      interventions an integral part of decision making in health services. This paper
      is the first in a series whose goal is to provide some basic principles of health
      economics that will allow practising physicians to understand better the economic
      relations between their practice of medicine, the health-care sector, and the
      national economy. Some of the most important principles described in this paper
      include opportunity costs, identifying the appropriate perspective, correctly
      categorising costs, and discounting costs and non-monetary benefits (eg, lives
      saved) over time. Economic analyses of medical interventions must also take into
      consideration the difference between efficacy and effectiveness. Efficacy is the
      maximum possible benefit, often achieved with carefully controlled trials, and
      effectiveness is the actual decrease in disease achieved when the intervention is
      applied over a large, non-homogeneous population. This introduction ends with
      three methods of assessing the costs and benefits of an intervention-namely, cost
      benefit, cost-effectiveness, and cost-utility analyses.

PMID- 11583769
TI  - Health in a 24-h society.
AB  - With increasing economic and social demands, we are rapidly evolving into a 24-h
      society. In any urban economy, about 20% of the population are required to work
      outside the regular 0800-1700 h working day and this figure is likely to
      increase. Although the increase in shiftwork has led to greater flexibility in
      work schedules, the ability to provide goods and services throughout the day and
      night, and possibly greater employment opportunities, the negative effects of
      shiftwork and chronic sleep loss on health and productivity are now being
      appreciated. For example, sleepiness surpasses alcohol and drugs as the greatest
      identifiable and preventable cause of accidents in all modes of transport.
      Industrial accidents associated with night work are common, perhaps the most
      famous being Chernobyl, Three Mile Island, and Bhopal.

PMID- 11583771
TI  - Thrifty genes and human obesity. Are we chasing ghosts?

PMID- 11583773
TI  - Adequacy of treatment in terminally ill patients.

PMID- 11583779
TI  - The failings of fellowship.

PMID- 11583781
TI  - Unprecedented forms of vanadium observed within the blood cells of Phallusia
      nigra using K-edge X-ray absorption spectroscopy.
AB  - Fits to the vanadium K-edge X-ray absorption spectra (XAS) of five whole blood
      cell samples from the tunicate Phallusia nigra revealed unprecedented forms of
      intracellular vanadium. Endogenous vanadium was divided between the V(III) ion
      (74.2+/-5.1% of total V) and the vanadyl ion [V(IV)=O](2+) (25.2+/-5.4% of total
      V). The V(III) fraction included both [V(H(2)O)(6)](3+) (36.7+/-5.5%) modeled as
      VCl(3) in 1 M HCl, and three previously unprecedented chelated V(III) forms
      (37.5+/-4.6%). Two of these could be represented by the model ligand environments
      V(acetylacetonate)(3) (17.9+/-3.2%) and K(3)V(catecholate)(3) (13.1+/-4.7%),
      implying DOPA-like complexation. The third chelated form was represented by the 7
      coordinate N(2)O(5) complex Na[V(edta)(H(2)O)] (8.0+/-1.8%). This coordination
      array, suggestive of a novel mononuclear V(III) protein site, contributed only to
      fits to samples 1, 2, 3 and 5, which were prepared in the presence of DTT.
      Endogenous V(IV) (25.2+/-5.4%) was principally modeled as VOCl(2) in 1 M HCl. EPR
      spectra (averages: A(parallel)=(1.842+/-0.006)x10(-2) cm(-1); A(
      perpendicular)=(0.718+/-0.007)x10(-2) cm(-1); g(parallel)=1.936+/-0.002; g(
      perpendicular)=1.990+/-0.001) confirmed the predominance of the aquated vanadyl
      ion. Blood cell sample five uniquely required the XAS spectrum of VOSO(4) in 0.1
      M H(2)SO(4) solution (13.0%) and of [OV(V)(pivalate)(3)] (3.1%) to successfully
      fit the XAS pre-edge energy region. This endogenous V(V) signal is also
      unprecedented. These results are compared with those of analogous fits to the
      blood cells of Ascidia ceratodes and may support assignment of P. nigra to a
      different genus.

PMID- 11583782
TI  - Syntheses, structures, stability, and insulin-like activities of
      peroxovanadium(V) complexes with a heteroligand.
AB  - Several peroxovanadium(V) complexes were prepared with a tripodal or a quasi
      tripodal tetradentate ligand. The structures of K(2)[VO(O(2))(nta)].2H(2)O and
      K[VO(O(2))(DL-cmhist)].H(2)O have been determined by X-ray crystallography (nta,
      nitrilotriacetate; cmhist, N-carboxymethylhistidinate). The structure of
      Cs[VO(O(2))(pda)].2H(2)O (pda, N-pyridylmethyliminodiacetate) has been estimated
      to be similar to that of K[VO(O(2))(DL-cmhist)].H(2)O. Each complex anion in
      these compounds adopts a distorted pentagonal bipyramidal structure, which is
      typical for heptacoordinate oxoperoxovanadium(V) complexes. The peroxide ion
      binds in a side-on fashion to the vanadium(V) center in the pentagonal plane. The
      peroxide anion in the cmhist complex dissociates rather easily in an acidic
      solution (pH approximately 3), while that in the other complexes stays intact
      under similar conditions. The in vitro insulin mimetic effect of the
      peroxovanadium(V) complexes has been evaluated by the inhibitory effect on free
      fatty acid (FFA) release in isolated rat adipocytes treated with epinephrine. The
      cmhist complex is effective, while the others are almost totally ineffective.

PMID- 11583783
TI  - Insulin mimetic effect of a tungstate cluster. Effect of oral administration of
      homo-polyoxotungstates and vanadium-substituted polyoxotungstates on blood
      glucose level of STZ mice.
AB  - Aqueous vanadate and aqueous tungstate have been known to mimic all or most of
      the actions of insulin in intact cell systems with respect to normalization of
      the blood glucose level. By carrying out oral administration in vivo experiments
      on the blood glucose level of streptozotocin (STZ)-induced diabetes (STZ mice),
      the insulin-mimetic (IM) effects of metal-oxide clusters of all-inorganic
      composition were examined using many types of polyoxometalates (POM) with and
      without vanadium substitution. Several homo-POM and vanadium-substituted POM
      showed hypoglycemic effects. The observed hypoglycemic effects indicated that POM
      with the Dawson structure [[alpha-P(2)W(18)O(62)](6-) (W-2), [alpha
      P(2)W(17)V(V)O(62)](7-) (V-19) and [alpha-1,2,3-P(2)W(15)V(V)(3)O(62)](9-) (V
      04)] are more effective than those with the Keggin structure [[alpha
      PW(12)O(40)](3-) (W-1), [alpha-PW(11)V(V)O(40)](4-) (V-01), [alpha-1,2
      PW(10)V(V)(2)O(40)](5-) (V-02), [alpha-1,2,3-PW(9)V(V)(3)O(40)](6-) (V-03) and
      [alpha-1,4,9-PW(9)V(V)(3)O(40)](6-) (V-13)]. The vanadate cluster [V(10)O(28)](6
      ) (V-15) also showed a hypoglycemic effect. (31)P and (51)V NMR measurements
      showed that the Dawson POM (W-2, V-04 and V-19) are stable in aqueous solution
      under the conditions used. The effect of all POM on the body weight of STZ mice
      was also examined. The decrease in body weight after administration of W-2 was
      much less than for V-19, V-04 and V-15. This suggests that not only monomeric
      tungstate and vanadate, but also the structure factors of tungstate and vanadate
      clusters, can play a significant role in their biological action.

PMID- 11583784
TI  - Detection of iron-containing proteins contributing to the cellular labile iron
      pool by a native electrophoresis metal blotting technique.
AB  - The labile iron pool (LIP) plays a role in generation of free radicals and is
      thus the target of chelators used for the treatment of iron overload. We have
      previously shown that the LIP is bound mostly to high molecular weight carriers
      (MW>5000). However, the iron does not remain associated with these proteins
      during native gel electrophoresis. In this study we describe a new method to
      reconstruct the interaction of iron with iron-binding proteins. Proteins were
      separated by native gradient polyacrylamide gel electrophoresis and transfered to
      polyvinilidene difluoride membrane under native conditions. The immobilized iron
      binding proteins are then labeled by 59Fe using a 'titrational blotting'
      technique and visualized by storage phosphorimaging. At least six proteins, in
      addition to ferritin and transferrin, are specifically labeled in cellular
      lysates of human erythroleukemic cells. This technique enables separation and
      detection of iron-binding proteins or other metal-protein complexes under near
      physiological conditions and facilitates identification of weak iron-protein
      complexes. Using a new native metal blotting method, we have confirmed that
      specific high molecular weight proteins bind the labile iron pool.

PMID- 11583785
TI  - A calorimetric study of 3d metal ions-acyclovir interactions. The 2
      hydroxyethoxymethyl group of acyclovir mimics the role of ribose in deoxy
      guanosine and guanosine promoting the coordination through N(7).
AB  - The equilibrium constants and enthalpic values of metal acyclovir complexes have
      been determined by calorimetry for Co(II) (log K=0.96+/-0.05, DeltaH (kJ/mol)=
      19.7+/-1.3), Ni(II) (log K=1.39+/-0.03, DeltaH (kJ/mol)=-21.5+/-1.0), Cu(II) (log
      K=1.83+/-0.03, DeltaH (kJ/mol)=-23.2+/-0.8) and Zn(II) (log K=0.71+/-0.06, DeltaH
      (kJ/mol)=-18.6+/-1.5). The equilibrium constants are similar to those of the
      divalent ions with guanosine and 2,9-dimethylpurine. By comparison with previous
      thermodynamic data, it can be shown that the 2-hydroxyethoxymethyl group promotes
      coordination through N(7) versus N(1) of the guanine ring for 3d metal ions.
      These results reveal that the 2-hydroxyethoxymethyl group placed on the purine
      ring of guanine in acyclovir causes a greater effect than that of the 9-methyl in
      purines and similar to or greater than that of the ribose moiety in guanosine.
      The 2-hydroxyethyoxymethyl group of acyclovir mimics the role of ribose in deoxy
      guanosine and guanosine promoting a similar coordination chemistry (with very
      close log K and DeltaH values) for acyclovir, deoxy-guanosine and guanosine with
      divalent metals.

PMID- 11583786
TI  - Theoretical evaluation of the hydrogen kinetic isotope effect on the first step
      of the methylmalonyl-CoA mutase reaction.
AB  - We have calculated hydrogen kinetic isotope effects (KIEs) for the first step of
      the methylmalonyl-CoA mutase reaction, including multidimensional tunneling
      correction at the zero curvature (ZCT) level, and compared them with the
      experimental values. Both alternative mechanisms of this step, concerted and
      stepwise, can be accommodated. It turned out to be essential to include Arg207
      hydrogen-bonded to the reactant in the mechanism predicting simultaneous breaking
      of the Co-C bond of AdoCbl and hydrogen atom transfer. The consequence of the
      stepwise mechanism is a much larger facilitation of the homolytic dissociation of
      the carbon-cobalt bond by the enzyme than currently appreciated; our results
      suggest lowering of the activation energy by about 23 kcal mol(-1). We have also
      shown that large hydrogen KIEs of tunneling origin do not necessarily break the
      Swain-Schaad equation. Furthermore, when this equation does not hold, the
      exponent may be smaller in the presence of tunneling than it is at the semi
      classical limit, indicating that nonclassical behavior may be a more common
      phenomenon than expected.

PMID- 11583788
TI  - A pharmacological link between epilepsy and anxiety?

PMID- 11583787
TI  - Comparison of the binding behavior of oxaliplatin, cisplatin and analogues to 5'
      GMP in the presence of sulfur-containing molecules by means of capillary
      electrophoresis and electrospray mass spectrometry.
AB  - Capillary electrophoresis as well as ESI-MS has been applied for investigating
      the influence of the sulfur-containing amino acids L-cysteine and L-methionine on
      the binding behavior of oxaliplatin (trans-R,R
      diaminocyclohexane(oxalato)platinum(II)), cisplatin (cis
      diamminedichloroplatinum(II)), carboplatin (cis-diammine-1,1
      cyclobutanedicarboxylatoplatinum(II)), cis-diammine(malonato)platinum(II) and cis
      diammine(2-hydroxymalonato)platinum(II) to 5'-GMP. The presence of L-methionine
      resulted in a different kind of adduct formation which involves ammine release
      due to the trans-effect of sulfur. In addition, the time-dependent behavior of
      the reaction with 5'-GMP changed significantly. Due to the high stability of the
      diaminocyclohexane (DACH) platinum fragment, oxaliplatin showed a completely
      different behavior in comparison to diammine platinum complexes. Formation of
      [Pt(DACH)(L-Met-S,N)](+) inhibits coordination of 5'-GMP. Displacement of L-Met
      by 5'-GMP does not occur. Differences concerning the mode of action of
      oxaliplatin are expected. Characterization of the analytes was performed by UV,
      NMR and mass spectrometry.

PMID- 11583789
TI  - Detoxification of a bacterial toxin by the toxin itself.

PMID- 11583790
TI  - Glial-neuronal interactions: a crescendo in the degree of CNS complexity.

PMID- 11583791
TI  - Platelets, polysomes and proteins.

PMID- 11583795
TI  - The real fat controller? A glucose-responsive transcription factor.

PMID- 11583806
TI  - The nigrostriatal dopamine system: a neglected target for 5-HT2C receptors.

PMID- 11583807
TI  - Protein kinases: tuners of the BKCa channel in smooth muscle.
AB  - Large-conductance, Ca(2+)-activated K(+) (BK(Ca)) channels in smooth muscle cells
      are unique because they integrate changes in both intracellular Ca(2+) and
      membrane potential. Protein kinases such as cAMP-dependent protein kinase, cGMP
      dependent protein kinase and protein kinase C can affect tissue function by
      'tuning' the apparent Ca(2+)- and/or voltage-sensitivity of the BK(Ca) channel to
      physiological changes in both Ca(2+) concentrations and membrane potential.
      However, despite the central importance of kinase-mediated modulation of BK(Ca)
      channels in different smooth muscle tissues, many key issues, including the sites
      and mechanisms of actions of protein kinases, remain unresolved. In this article,
      the role of protein kinases in the regulation of BK(Ca) channels is discussed.

PMID- 11583808
TI  - Protein-protein interactions at G-protein-coupled receptors.
AB  - The basic module of signal transduction that involves G-protein-coupled receptors
      is usually portrayed as comprising a receptor, a heterotrimeric G protein and an
      effector. It is now well established that regulated interactions between
      receptors and arrestins, and between G proteins and regulators of G-protein
      signalling alter the effectiveness and kinetics of information transfer. However,
      more recent studies have begun to identify a host of other proteins that interact
      selectively with individual receptors at both the intracellular and extracellular
      face of the membrane. Although the functional relevance of many of these
      interactions is only beginning to be understood, current information indicates
      that these interactions might determine receptor properties, such as cellular
      compartmentalization or signal selection, and can promote protein scaffolding
      into complexes that integrate function.

PMID- 11583809
TI  - Interactions between presynaptic Ca2+ channels, cytoplasmic messengers and
      proteins of the synaptic vesicle release complex.
AB  - Influx of Ca(2+) through presynaptic voltage-gated Ca(2+) channels is a key step
      in rapid neurotransmitter release. The amount of Ca(2+) entering through these
      channels is modulated by a plethora of intracellular messenger molecules,
      including betagamma-subunits of G proteins, and protein kinases. In addition,
      Ca(2+) channels bind physically to proteins of the vesicle-release machinery in a
      Ca(2+)-dependent manner, which can, in turn, regulate the activity of Ca(2+)
      channels. Recent evidence suggests that second messengers and presynaptic vesicle
      release proteins do not regulate Ca(2+) channel activity as independent entities,
      but that there is extensive crosstalk between these two mechanisms. The complex
      interactions between second messengers, vesicle-release proteins and voltage
      gated Ca(2+) channels might provide multiple avenues for fine-tuning Ca(2+) entry
      into the presynaptic terminal and, consequently, neurotransmission.

PMID- 11583810
TI  - Use of transgenic mice to study voltage-dependent Ca2+ channels.
AB  - During the past decade a great number of genes encoding high- and low-voltage
      dependent Ca(2+) channels and their accessory subunits have been cloned. Studies
      of Ca(2+) channel structure-function relationships and channel regulation using
      cDNA expression in heterologous expression systems have revealed intricate
      details of subunit interaction, regulation of channels by protein kinase A (PKA)
      and protein kinase C (PKC), drug binding sites, mechanisms of drug action, the
      ion conduction pathway and other aspects of channel function. In recent years,
      however, we have arrived at the brink of an entirely new strategy to study Ca(2+)
      channels by overexpressing or knocking out genes encoding these channels in
      transgenic mice. In this article, various models of gene knockout or gene
      overexpression will be discussed. This new approach will reveal many secrets
      regarding Ca(2+) channel regulation and the control of Ca(2+)-dependent cellular
      processes.

PMID- 11583811
TI  - Heterodimerization of G-protein-coupled receptors: pharmacology, signaling and
      trafficking.
AB  - Although classical models predict that G-protein-coupled receptors (GPCRs)
      function as monomers, several recent studies acknowledge that GPCRs exist as
      dimeric or oligomeric complexes. In addition to homodimers, heterodimers between
      members of the GPCR family (both closely and distantly related) have been
      reported. In some cases heterodimerization is required for efficient agonist
      binding and signaling, and in others heterodimerization appears to lead to the
      generation of novel binding sites. In this article, the techniques used to study
      GPCR heterodimers, and the 'novel pharmacology' and functional implications
      resulting from heterodimerization will be discussed.

PMID- 11583812
TI  - Unbalanced research.

PMID- 11583814
TI  - A new functional domain of Bcl6 family that recruits histone deacetylases.
AB  - The proto-oncogene Bcl6 and its family gene, BAZF, encode a sequence-specific
      transcriptional repressor which contains the BTB/POZ domain in NH(2)-terminal
      region and zinc finger motifs in COOH-terminal region. The BTB/POZ domain and the
      middle portion of Bcl6 and BAZF are known to display transrepressor activity.
      Since we have identified the identical 17-amino acid (aa) sequence in the middle
      portion of Bcl6 and BAZF, the 17aa region may be another repressive domain of the
      middle portion. The reporter gene assay indicates that the 27aa sequence
      including the 17aa region recruits histone deacetylases to express transrepressor
      activity. Furthermore, overexpression of Bcl6 or Bcl6(POZ-) (Bcl6 deleted with
      the BTB/POZ domain) induced apoptosis in NIH3T3 cells, and the apoptosis was
      inhibited by the addition of histone deacetylase inhibitor in the culture.
      However, apoptosis was not induced in NIH3T3 cells by overexpression of Bcl6(POZ
      ) deleted with the 17aa region. These results indicate that the 17aa region in
      the middle portion of Bcl6 is a functional domain of transrepressor activity and
      is responsible for inducibility of apoptosis in NIH3T3 cells.

PMID- 11583813
TI  - Hypoxic enhancement of type IV collagen secretion accelerates adipose conversion
      of 3T3-L1 fibroblasts.
AB  - Hypoxic modulation of collagen metabolism appears to be related to pathogenesis
      of many diseases such as fibrosis of connective tissue after injury and
      scleroderma. Since most of our understanding of how procollagen assembles within
      the cell has come from studies on cells cultured under normoxia, it may not be
      helpful for the etiology of the diseases observed in peripheral tissues under
      hypoxic conditions. As an experimental model for the hypoxic modulation of
      collagen metabolism, we cultured 3T3-L1 fibroblasts under low partial oxygen
      pressure and found that hypoxia enhances secretion of type IV collagen 10-fold
      and accelerates adipose conversion of the cells. The enhanced secretion of type
      IV collagen was not accompanied by an appreciable increase of alpha1(IV) and
      alpha2(IV) mRNAs. Prolyl 4-hydroxylase alpha increased only 3-fold under hypoxia.
      We suggest that hypoxia creates an environment of prolyl 4-hydroxylase
      alpha(2)beta(2) tetramers favorable for the folding of type IV procollagen which
      has many interruptions of the Gly-Xaa-Yaa repeat.

PMID- 11583815
TI  - Parathyroid hormone activation of map kinase in rat duodenal cells is mediated by
      3',5'-cyclic AMP and Ca(2+).
AB  - In a previous study, we demonstrated that parathyroid hormone (PTH) stimulates in
      rat duodenal cells (enterocytes) the phosphorylation and activity of
      extracellular signal-regulated mitogen-activated protein kinase (MAPK) isoforms
      ERK1 and ERK2. As PTH activates adenylyl cyclase (AC) and phospholipase C and
      increases intracellular Ca(2+) in these cells, in the present study we evaluated
      the involvement of cAMP, Ca(2+) and protein kinase C (PKC) on PTH-induced MAPK
      activation. We found that MAPK phosphorylation by the hormone did not depend on
      PKC activation. PTH response could, however, be mimicked by addition of forskolin
      (5-15 microM), an AC activator, or Sp-cAMP (50-100 microM), a cAMP agonist, and
      suppressed to a great extent by the AC inhibitor, compound Sq-22536 (0.2-0.4 mM)
      and the cAMP antagonist Rp-cAMP (0.2 mM). Removal of external Ca(2+) (EGTA 0.5
      mM), chelation of intracellular Ca(2+) with BAPTA (5 microM), or blockade of L
      type Ca(2+)-channels with verapamil (10 microM) significantly decreased PTH
      activation of MAPK. Furthermore, a similar degree of phosphorylation of MAPK was
      elicited by the Ca(2+) mobilizing agent thapsigargin, the Ca(2+) ionophore
      A23187, ionomycin and membrane depolarization with high K(+). Inclusion of the
      calmodulin inhibitor fluphenazine (50 microM) did not prevent hormone effects on
      MAPK. Taken together, these results indicate that cAMP and Ca(2+) play a role
      upstream in the signaling mechanism leading to MAPK activation by PTH in rat
      enterocytes. As Ca(2+) and cAMP antagonists did not block totally PTH-induced
      MAPK phosphorylation, it is possible that linking of the hormone signal to the
      MAPK pathway may additionally involve Src, which has been previously shown to be
      rapidly activated by PTH. Of physiological significance, in agreement with the
      mitogenic role of the MAPK cascade, PTH increased enterocyte DNA synthesis, and
      this effect was blocked by the specific inhibitor of MAPK kinase (MEK) PD098059,
      indicating that hormone modulation of MAPK through these messenger systems
      stimulates duodenal cell proliferation.

PMID- 11583816
TI  - Phosphorylation of proteins and apoptosis induced by c-Jun N-terminal kinase1
      activation in rat cardiomyocytes by H(2)O(2) stimulation.
AB  - Cytokines and various cellular stresses are known to activate c-Jun N-terminal
      kinase-1 (JNK1), which is involved in physiological function. Here, we
      investigate the activation of JNK1 by oxidative stress in H9c2 cells derived from
      rat cardiomyocytes. H(2)O(2) (100 microM) significantly induces the tyrosine
      phosphorylation of JNK1 with a peak 25 min after the stimulation. The amount of
      JNK1 protein remains almost constant during stimulation. Immunocytochemical
      observation shows that JNK1 staining in the nucleus is enhanced after H(2)O(2)
      stimulation. To clarify the physiological role of JNK1 activation under these
      conditions, we transfected antisense JNK1 DNA into H9c2 cells. The antisense DNA
      (2 microM) inhibits JNK1 expression by 80% as compared with expression in the
      presence of the sense DNA, and significantly blocks H(2)O(2)-induced cell death.
      Consistent with the decrease in cell number, we detected condensation of the
      nuclei, a hallmark of apoptosis, 3 h after H(2)O(2) stimulation in the presence
      of the sense DNA for JNK1. The antisense DNA of JNK1 inhibits the condensation of
      nuclei by H(2)O(2). Under these conditions, the H(2)O(2)-induced phosphorylation
      of proteins with molecular masses of 55, 72, and 78 kDa is blocked by treatment
      with the antisense DNA for JNK1 as compared with the sense DNA for JNK1. These
      findings suggest that JNK1 induces apoptotic cell death in response to H(2)O(2),
      and that the cell death may be involved in the phosphorylations of 55, 72, and 78
      kDa proteins induced by JNK1 activation.

PMID- 11583817
TI  - Characteristics and distribution of endogenous RFamide-related peptide-1.
AB  - We have recently identified RFamide-related peptide (RFRP) gene that would encode
      three peptides (i.e., RFRP-1, -2, and -3) in human and bovine, and demonstrated
      that synthetic RFRP-1 and -3 act as specific agonists for a G protein-coupled
      receptor OT7T022. However, molecular characteristics and tissue distribution of
      endogenous RFRPs have not been determined yet. In this study, we prepared a
      monoclonal antibody for the C-terminal portion of rat RFRP-1. As this antibody
      could recognize a consensus sequence among the C-terminal portions of rat, human,
      and bovine RFRP-1, we purified endogenous RFRP-1 from bovine hypothalamus on the
      basis of immunoreactivity to the antibody. The purified bovine endogenous RFRP-1
      was found to have 35-amino-acid length that corresponds to 37-amino-acid length
      in human and rat. We subsequently constructed a sandwich enzyme immunoassay using
      the monoclonal antibody and a polyclonal antibody for the N-terminal portion of
      rat RFRP-1, and analyzed the tissue distribution of endogenous RFRP-1 in rats.
      Significant levels of RFRP-1 were detected only in the central nervous system,
      and the highest concentration of RFRP-1 was detected in the hypothalamus. RFRP-1
      positive nerve cells were detected in the rat hypothalamus by immunohistochemical
      analyses using the monoclonal antibody. In culture, RFRP-1 lowered cAMP
      production in Chinese hamster ovary cells expressing OT7T022 and it was abolished
      by pre-treatment with pertussis toxin, suggesting that OT7T022 couples G(i)/G(o)
      in the signal transduction pathway.

PMID- 11583818
TI  - Factor(s) released by glucose-deprived astrocytes enhance glucose transporter
      expression and activity in rat brain endothelial cells.
AB  - Glucose transporter (GLUT) expression and regulation were studied in rat brain
      endothelial cells in primary culture (RBEC) and in immortalised RBE4 cells.
      Immunoblotting analysis showed a low expression of the endothelium-specific GLUT1
      in RBEC and RBE4 cells compared to isolated brain capillaries. RBEC and RBE4
      cells also expressed the GLUT3 isoform, whereas it was not present in isolated
      brain capillaries. No change in GLUT expression was observed in endothelial cells
      treated with astrocyte-conditioned medium. However, treatment with conditioned
      medium obtained from glucose-deprived astrocytes increased endothelial GLUT1
      expression and glucose uptake. These results suggest that astrocytes submitted to
      hypoglycaemic conditions may release factor(s) that increase glucose uptake
      through the blood-brain barrier.

PMID- 11583819
TI  - Protein kinase C regulation of cell spreading in the molluscan Biomphalaria
      glabrata embryonic (Bge) cell line.
AB  - Cellular adhesion and spreading are critical components involved in the processes
      of cell and tissue development, and immune responses in molluscs, but at present,
      little is known regarding the signaling pathways involved in these basic cellular
      functions. In the present study, the molluscan Biomphalaria glabrata embryonic
      (Bge) cell line was used as an in vitro model to study the signal transduction
      pathways regulating molluscan cell adhesion and spreading behavior. Western blot
      analysis using antibodies specific to mitogen-activated protein kinase (MAPK)
      revealed the presence of an MAPK-like immunoreactive protein in Bge cells, that
      was phosphorylated upon exposure to phorbol myristate acetate (PMA). Moreover,
      Bge cell treatment with inhibitors of protein kinase C (PKC), Ras and MAPK kinase
      (Mek) suppressed PMA-induced expression of activated MAPK, suggesting that PKC-,
      Ras- and Mek-like molecules may be acting upstream of MAPK. Similarly, in vitro
      Bge cell-spreading assays were performed in conjunction with the same panel of
      inhibitors to determine the potential involvement of PKC, Ras and Mek in cellular
      adhesion/spreading. Results revealed a similar pattern of inhibition of cell
      spreading behavior strongly implying that the Bge cell spreading also may be
      regulated through a MAPK-associated signal transduction pathway(s) involving
      proteins similar to PKC, Ras and Mek.

PMID- 11583820
TI  - Characterization of basal nitric oxide production in living cells.
AB  - Nitric oxide (NO) is an important modulator of immune, endocrine and neuronal
      functions; however, measuring physiological levels of NO in cell cultures is
      generally difficult because of the lack of suitable methodologies. We have
      selected three cell lines from different origins: the neuroblastoma-derived
      Neuro2A (N2A), the cholinergic SN56 and the non-neuronal COS-1. We first
      demonstrated the presence of NADPH-diaphoretic activity, a potential marker of
      the NO-synthesizing (NOS) enzyme. By immunocytochemistry, using specific
      antibodies for each NOS subtype, we observed that subtype I was present in all
      cell lines and that subtype II was present in COS-1 and N2A cell lines. The
      presence of these NOS subtypes was further verified by Western blot analysis.
      Control cells treated with DAF-2 DA exhibited significant fluorescent levels
      corresponding to basal NO production. The subcellular distribution of the
      synthesizing enzyme was consistent with the NO-fluorescence signal; whereas,
      fixation affected the subcellular pattern of NO fluorescence signal. Addition of
      NOS inhibitors or NO scavengers to the incubation medium reduced the intensity of
      the NO fluorescence signal in a concentration-dependent manner. Conversely,
      increasing concentrations of a NO donor, or incident light, increased the
      fluorescence intensity. Our observation of NO production and distribution using
      the DAF-2 method has a direct impact on studies using these cell lines.

PMID- 11583821
TI  - Infectious diseases, host defence and the training of residents in internal
      medicine.

PMID- 11583822
TI  - Infections with non-tuberculous mycobacteria and salmonellae in patients with
      genetic defects in the interleukin-12/interferon-gamma-mediated pathway of
      macrophage activation.

PMID- 11583823
TI  - Photo quiz: a cerebral contrast enhancing lesion in a patient with impaired
      cellular immunity.

PMID- 11583824
TI  - Case report: an unusual presentation of Yersinia enterocolitica infection.
AB  - We report on a 30-year-old Dutch marine who was stationed in Eritrea and who was
      repatriated because of acute paralytic small-bowel ileus. The disease course was
      short and without signs of infection. After diagnostic work-up, we diagnosed
      Yersinia enterocolitica infection. To our knowledge this is the first reported
      case of Yersinia enterocolitica infection causing paralytic ileus in an adult.

PMID- 11583825
TI  - The role of high density lipoprotein in sepsis.

PMID- 11583826
TI  - Diagnosis and treatment of HIV-associated nephropathy.
AB  - Human immunodeficiency virus-associated nephropathy (HIVAN) is a distinct clinico
      pathological syndrome that occurs almost exclusively in black patients with an
      AIDS defining diagnosis. It is characterized by rapidly progressive renal failure
      with a severe nephrotic syndrome. The renal biopsy typically shows a collapsing
      glomerular sclerosis and variable tubulo-interstitial nephritis. The pathogenesis
      most likely involves infection of renal tubular and epithelial cells with HIV.
      The use of ACE-inhibitors and steroids may slow down the progression to end-stage
      renal failure. With the introduction of highly active anti-retroviral therapy,
      HIVAN may now be treated effectively although clinical data are so far limited to
      case-reports.

PMID- 11583827
TI  - Hereditary periodic fever syndromes.
AB  - Hereditary periodic fever syndromes are defined by recurrent attacks of
      generalised inflammation for which no infectious or auto-immune cause can be
      identified. For most of these disorders, the molecular basis has recently been
      elucidated. This has opened the prospect of novel therapeutic approaches.
      Familial Mediterranean fever (FMF) is caused by mutations in the MEFV gene.
      Pathogenesis is poorly understood. The clinical severity is in part related to
      the mutations involved. Tumour necrosis factor receptor-1-associated periodic
      syndrome (TRAPS) is caused by mutations in the TNFRSF1A gene. This results in
      decreased serum levels soluble TNF-receptor leading to inflammation due to
      unopposed TNF-alpha action. Results of treatment with recombinant TNF-receptor
      analogues are promising. The hyper IgD periodic fever syndrome (HIDS) is caused
      by mutations in the MVK gene, leading to mevalonate kinase deficiency. The
      pathogenesis remains unclear. Muckle-Wells syndrome (MWS) and familial cold
      urticaria (FCU) are probably allelic disorders. The gene has been located, but
      not identified.

PMID- 11583828
TI  - Determinants of Staphylococcus aureus nasal carriage.
AB  - This article aims to review what is currently known of the host and bacterial
      factors determining S. aureus nasal carriage, including recent developments and
      future prospects.

PMID- 11583829
TI  - Common variable immunodeficiency (CVID) in a family: an autosomal dominant mode
      of inheritance.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is characterised by a late
      onset deficiency of immunoglobulins resulting in recurrent infectious and non
      infectious ailments. Most cases are sporadic but occasional familial clustering
      has been described. We present an extensively affected family with CVID in three
      consecutive generations. METHODS: We conducted a study in this family to
      establish clinical phenotype, to clarify the mode of inheritance and to attempt
      to characterise the immune disturbance by determining immunoglobulin
      concentrations and B- and T-cell analysis. RESULTS: We describe six patients with
      CVID in three consecutive generations. In addition, we encountered 10 family
      members with dysimmunoglobulinemia. B-cell counts were normal, but T-cell
      analysis showed slightly abnormal results. CONCLUSIONS: The six cases of overt
      late onset hypogammaglobulinemia are compatible with an autosomal dominant mode
      of inheritance. The family members with dysimmunoglobulinemia may be at risk to
      develop overt CVID in the future, in view of the gradual course of progression of
      the disease in the clinically affected family members. B- and T-cell analysis are
      inconclusive though may support a possible defect in T-cell function to be
      involved. To further study this remarkable family and attempt to clarify
      pathogenesis, we are planning DNA linkage analysis in the near future.

PMID- 11583830
TI  - Multifocal osteomyelitis caused by nontuberculous mycobacteria in patients with a
      genetic defect of the interferon-gamma receptor.
AB  - We describe three patients with multifocal osteomyelitis caused by Mycobacterium
      avium and a family history of one or more first degree family members diagnosed
      with various clinical presentations of infections with nontuberculous
      mycobacteria. There was a significant delay in the diagnosis and they had a
      protracted course of their illness, which responded only slowly to prolonged
      multi-drug treatment. In one patient, additional treatment with interferon-gamma
      (IFN-gamma) was necessary. Macrophages of these patients had decreased in vitro
      responsiveness to IFN-gamma. Genomic sequencing revealed that these patients and
      their affected family members were heterozygous for a previously described
      dominant negative mutation in the gene encoding the IFN-gamma binding receptor-1
      chain. The clinical presentations of the infections with nontuberculous
      mycobacteria in these families, with spread limited to skin, bone and lymph
      nodes, is discussed in the light of the immune mechanisms that are responsible
      for the clearance of otherwise poorly pathogenic environmental mycobacteria.

PMID- 11583831
TI  - Nosocomial transmission of tuberculosis to a nurse demonstrated by means of
      spoligotyping of a formalin-fixed bronchial biopsy.
AB  - BACKGROUND: Tuberculosis was diagnosed in a student nurse. The source of
      infection was unknown and no positive culture was available. METHODS: The
      diagnosis of tuberculous bronchitis was established on the grounds of a positive
      Mantoux test, the pathology of a bronchial biopsy and the results of a CT scan of
      the thorax. Spoligotyping of, for example, formalin-fixed tissue makes it
      possible to establish the diagnosis in a later phase after all. RESULTS: Cultures
      for Mycobacterium tuberculosis were not performed for the student nurse and Ziehl
      Neelsen staining of the formalin-fixed bronchial biopsy was negative. The final
      tuberculosis diagnosis was confirmed by a PCR fingerprint technique, i.e.,
      spoligotyping of a formalin-fixed biopsy specimen. By means of contact
      investigation and identification of the strain via spoligotyping, comparison of
      the spoligo patterns made it possible to treat both the patient and those
      infected by this person correctly. CONCLUSIONS: When there is a pronounced
      suspicion of tuberculosis and a microbiological culture is not available, it is
      recommended that supplementary spoligotyping of clinical specimens be carried
      out. The purpose is to confirm the diagnosis, trace the presumed source case and
      indirectly to provide information on the drug susceptibility of the relevant M.
      tuberculosis strain.

PMID- 11583832
TI  - Brucellar spondylitis and meningoencephalitis: a case report.
AB  - Brucellosis, a zoonosis with a worldwide distribution, is a systemic infection
      that can present with involvement of both nervous and musculoskeletal systems. We
      report a case of spondylitis and meningoencephalitis and describe the clinical
      features, and difficulties in treatment. Osteoarticular complications of
      brucellosis are common but involvement of the nervous system is rare and it
      should be included in the differential diagnosis of any obscure neurologic
      disorder.

PMID- 11583833
TI  - Resonance energy transfer study of peptide-lipid complexes.
AB  - Resonance energy transfer involving tryptophan as a donor and anthrylvinyl
      labeled phosphatidylcholine (AV-PC), 3-methoxybenzanthrone (MBA) and 8-anilino-1
      naphthalene sulfonic acid (ANS) as acceptors has been examined to obtain
      information on the structure of peptide-lipid systems consisting of 18A or Ac-18A
      NH(2) peptides and large unilamellar phosphatidylcholine vesicles. The lower and
      upper limits for the tryptophan distance from the bilayer midplane have been
      assessed in terms of the models of energy transfer in two-dimensional systems,
      taking into account orientational effects. Evidence for the existence of
      preferential orientations of Ac-18A-NH(2) with respect to the lipid-water
      interface has been obtained.

PMID- 11583834
TI  - Characterization of oligonucleotide/lipid interactions in submicron cationic
      emulsions: influence of the cationic lipid structure and the presence of PEG
      lipids.
AB  - We have recently described how oligonucleotide (ON) stability and release from
      O/W cationic emulsions are governed by the lipid composition. The aim of the
      present paper was to investigate the properties of the ON/lipid complexes through
      fluorescence resonance energy transfer (FRET), size, surface tension measurements
      and cryomicroscopy. Starting from a typical emulsion containing stearylamine as a
      cationic lipid, the influence of the lipid structure (monocationic molecules
      bearing mono or diacyl chains, or polycations) as well as of the presence of
      PEGylated lipids, were studied. The presence of a positive charge on the droplet
      surface clearly contributed to enhance the ON interaction with lipid monolayers
      and to bring the ON molecules closer to the interface. Hydrophobic interactions
      through the acyl chains were shown to further enhance the anchorage of the
      ON/lipid complexes. In contrast, the incorporation of PEGylated lipids acted as a
      barrier against the establishment of electrostatic bindings, the
      polyethyleneglycol chains acting themselves as interaction sites for the ON
      leading to hydrophilic complexes. Similar features were observed for the
      polycationic lipid, and cryomicroscopy revealed the existence of bridges of
      various intensities between the droplets of the emulsion containing either PEG or
      the polycation, probably because of the configuration of the ON at the interface.

PMID- 11583835
TI  - Molecular dynamics simulation and essential dynamics study of mutated
      plastocyanin: structural, dynamical and functional effects of a disulfide bridge
      insertion at the protein surface.
AB  - A molecular dynamics simulation (1.1 ns) at 300 K, of fully hydrated Ile21Cys,
      Glu25Cys plastocyanin mutant has been performed to investigate the structural,
      dynamical and functional effects of a disulfide bridge insertion at the surface
      of the protein. A detailed analysis of the root mean square fluctuations, H
      bonding pattern and dynamical cross-correlation map has been performed. An
      essential dynamics method has also been applied as complementary analysis to
      identify concerted motions (essential modes), that could be relevant to the
      electron transfer function. The results have been compared with those previously
      obtained for wild-type plastocyanin and have revealed that the mutant shows a
      different pattern of H-bonds, with several interactions lost and a higher
      flexibility, especially around the electron transfer copper site. The analysis of
      dynamical cross-correlation map and of essential modes, has shown that the mutant
      performs different functional concerted motions, which might be related to the
      binding recognition with its electron transfer partners in comparison with the
      wild-type protein.

PMID- 11583836
TI  - On the elastic properties of tetramethylrhodamine F-actin.
AB  - (Iodoacetamido)tetramethylrhodamine disrupts F-actin. At the 1:1 fluorophore to
      actin (as monomer) ratio approximately 80% of the protein becomes non
      sedimentable. The fluorescent, non-sedimentable actin copolymerizes with G-actin
      to yield fluorescent filaments. The tensile strength of these filaments changes
      with the ratio of the fluorescent non-sedimentable actin to the G-actin, being
      1.6 pN, 2.9 pN and 3.6 pN at the 1/4, 2/3 and 1/1 ratios, respectively. These
      tensile strengths are approximately two orders of magnitude lower than those
      obtained by decoration of F-actin with phalloidin.

PMID- 11583837
TI  - Volumetric characterization of the hydration properties of heterocyclic bases and
      nucleosides.
AB  - We have determined the partial molar volumes, expansibilities, and adiabatic
      compressibilities of six heterocyclic nucleic acid bases, five ribonucleosides,
      and six 2'-deoxyribonucleosides within the temperature range 18-55 degrees C. We
      interpret the resulting data in terms of the hydration of the component
      hydrophobic and polar atomic groups. From our temperature-dependent volumetric
      studies, we found that the total contraction of water caused by polar groups of
      each individual heterocyclic base and nucleoside depends on the proximity and
      chemical nature of other functional groups of the solute. In addition, the
      compressibility contributions of polar groups vary greatly in sign and magnitude
      depending on the surrounding functional groups. In agreement with previous
      studies, our results are suggestive of little or no interaction between the sugar
      and base moieties of a nucleoside. In general, our data shed light into the
      hydration properties of individual heterocyclic bases and nucleosides, which may
      have significant implications for the sequence-dependent hydration of nucleic
      acids. We discuss the potential importance of our results for developing an
      understanding of the role that solvent plays in the stabilization/destabilization
      of nucleic acid structures.

PMID- 11583838
TI  - Ubiquinone biosynthesis in microorganisms.
AB  - The quinoid nucleus of the benzoquinone, ubiquinone (coenzyme Q; Q), is derived
      from the shikimate pathway in bacteria and eukaryotic microorganisms. Ubiquinone
      is not considered a vitamin since mammals synthesize it from the essential amino
      acid tyrosine. Escherichia coli and other Gram-negative bacteria derive the 4
      hydroxybenzoate required for the biosynthesis of Q directly from chorismate. The
      yeast, Saccharomyces cerevisiae, can either form 4-hydroxybenzoate from
      chorismate or tyrosine. However, unlike mammals, S. cerevisiae synthesizes
      tyrosine in vivo by the shikimate pathway. While the reactions of the pathway
      leading from 4-hydroxybenzoate to Q are the same in both organisms the order in
      which they occur differs. The 4-hydroxybenzoate undergoes a prenylation, a
      decarboxylation and three hydroxylations alternating with three methylation
      reactions, resulting in the formation of Q. The methyl groups for the methylation
      reactions are derived from S-adenosylmethionine. While the prenyl side chain is
      formed by the 2-C-methyl-D-erythritol 4-phosphate (non-mevalonate) pathway in E.
      coli, it is formed by the mevalonate pathway in the yeast.

PMID- 11583839
TI  - Cytolethal distending toxin (CDT): a bacterial weapon to control host cell
      proliferation?
AB  - Cytolethal distending toxins (CDT) constitute a family of genetically related
      bacterial protein toxins able to stop the proliferation of numerous cell lines.
      This effect is due to their ability to trigger in target cells a signaling
      pathway that normally prevents the transition between the G2 and the M phase of
      the cell cycle. Produced by several unrelated Gram-negative mucosa-associated
      bacterial species, CDTs are determined by a cluster of three adjacent genes
      (cdtA, cdtB, cdtC) encoding proteins whose respective role is not yet fully
      elucidated. The CDT-B protein presents sequence homology to several mammalian and
      bacterial phosphodiesterases, such as DNase I. The putative nuclease activity of
      CDT-B, together with the activation by CDT of a G2 cell cycle checkpoint,
      strongly suggests that CDT induces an as yet uncharacterized DNA alteration.
      However, the effective entry of CDT into cells and subsequent translocation into
      the nucleus have not yet been demonstrated by direct methods. The relationship
      between the potential DNA-damaging properties of this original family of toxins
      and their role as putative virulence factors is discussed.

PMID- 11583840
TI  - Role of flagellum and chemotactic motility of Vibrio anguillarum for phagocytosis
      by and intracellular survival in fish macrophages.
AB  - The role of the flagellum and chemotactic motility of Vibrio anguillarum for
      phagocytosis by and intracellular survival in fish macrophages was determined
      using a wild-type strain, a mutant without the flagellum, a mutant with a
      truncated flagellum and a non-chemotactic mutant. For all strains, the numbers of
      intracellular bacteria were relatively low and fell steadily during the
      observation period. The presence of a flagellum did not influence the uptake by
      the macrophages, but the smooth swimming phenotype of a non-chemotactic mutant
      increased its intracellular presence. We suggest that this is due to an increased
      collision between the mutant and the macrophage, due to a higher average speed of
      the non-chemotactic mutant.

PMID- 11583841
TI  - Differential expression of Pmp10 in cell culture infected with Chlamydia
      pneumoniae CWL029.
AB  - The complete genome of Chlamydia pneumoniae contains a total of 21 genes encoding
      polymorphic membrane proteins (Pmp). From this large Pmp family three genes,
      pmp8, pmp10 and pmp11, were cloned and antibodies against recombinant full-length
      Pmp proteins were produced. Indirect immunofluorescence microscopy of HEp-2 cells
      infected with C. pneumoniae CWL029 was performed with the Pmp antibodies in
      combination with a Chlamydia-specific anti-lipopolysaccharide (LPS) antibody.
      This double staining technique clearly showed that expression of Pmp10 was
      differential. Additional double staining with monoclonal antibodies to the
      surface of C. pneumoniae elementary bodies and the anti-LPS antibody resulted in
      identification of seven monoclonal antibodies that reacted identically to the
      Pmp10 antibody indicating that Pmp10 is an immunodominant protein. Finally, the
      molecular mechanism responsible for differential expression is suggested to be
      variation in the guanine residues in the polyG tract of pmp10.

PMID- 11583842
TI  - Inactivation of tissue inhibitor of metalloproteinases-1 (TIMP-1) by
      Porphyromonas gingivalis.
AB  - In response to periodontal inflammation, host cells release matrix
      metalloproteinases (MMPs) that contribute to periodontal tissue breakdown unless
      the tissue inhibitors of metalloproteinases (TIMPs) neutralize their activity. In
      this study, the capacity of Porphyromonas gingivalis to inactivate TIMP-1 was
      investigated. Proteolytic digestion of TIMP-1 was monitored by SDS-PAGE and
      Western immunoblotting. Planktonic cells and biofilms of P. gingivalis degraded
      TIMP-1 with production of several lower molecular mass fragments. Incorporation
      of human serum in the assay mixture had no effect on the degradation of TIMP-1 by
      P. gingivalis, whereas a cysteine proteinase inhibitor caused a complete
      inhibition. Using a fluorogenic assay, it was found that TIMP-1 treated with P.
      gingivalis lost its capacity to inhibit MMP-9 activity. This study revealed the
      potential of P. gingivalis to inactivate TIMP-1 through proteolytic degradation.
      This phenomenon may contribute to increasing significantly the level of active
      MMPs in affected periodontal sites and subsequently favor tissue destruction.

PMID- 11583843
TI  - Fastidian gum: the Xylella fastidiosa exopolysaccharide possibly involved in
      bacterial pathogenicity.
AB  - The Gram-negative bacterium Xylella fastidiosa was the first plant pathogen to be
      completely sequenced. This species causes several economically important plant
      diseases, including citrus variegated chlorosis (CVC). Analysis of the genomic
      sequence of X. fastidiosa revealed a 12 kb DNA fragment containing an operon
      closely related to the gum operon of Xanthomonas campestris. The presence of all
      genes involved in the synthesis of sugar precursors, existence of
      exopolysaccharide (EPS) production regulators in the genome, and the absence of
      three of the X. campestris gum genes suggested that X. fastidiosa is able to
      synthesize an EPS different from that of xanthan gum. This novel EPS probably
      consists of polymerized tetrasaccharide repeating units assembled by the
      sequential addition of glucose-1-phosphate, glucose, mannose and glucuronic acid
      on a polyprenol phosphate carrier.

PMID- 11583844
TI  - Genetic analysis of conservation and variation of lipooligosaccharide expression
      in two L8-immunotype strains of Neisseria meningitidis.
AB  - Neisseria meningitidis strains A1 and M978 both express the lipooligosaccharide
      (LOS) L8 immunotype [Gu et al., J. Clin. Microbiol. 30 (1992) 2047-2053]. Under
      different growth conditions, strain A1 did not change its LOS profile whereas
      strain M978 produced variable LOS profiles on SDS-PAGE. To understand the genetic
      basis of LOS conservation and variation, their lgt locus encoding
      glycosyltransferases responsible for the biosynthesis of the alpha-chain of LOS
      was analyzed. Strain A1 possessed only two genes, lgtA and lgtH, at the lgt
      locus. The lgtA gene was inactivated due to a frameshift mutation; thus strain A1
      expressed only L8 LOS. In contrast, strain M978 contained five genes lgtZ, lgtC,
      lgtA, lgtB and lgtE at this locus, thus it had a potential to express L1, L3,7 in
      addition to the L8 LOS. The data showed that strain A1 is a better reference
      strain for the L8 immunotype because of the stability of L8 LOS expression
      resulting from its unique lgt locus. In addition, these two strains had two new
      genetic organizations, lgtAH and lgtZCABE, compared to the reported gene
      organization at the lgt locus in N. meningitidis.

PMID- 11583845
TI  - Sulfophthalimide as major metabolite formed from sulfonated phthalocyanine dyes
      by the white-rot fungus Bjerkandera adusta.
AB  - The reaction products formed during the decolorization of the sulfophthalocyanine
      textile dyes Reactive blue 15 (RB15) and Reactive blue 38 (RB38) by the white-rot
      fungus Bjerkandera adusta were analyzed by high-performance liquid chromatography
      with diode array detection and with liquid chromatography-electrospray ionization
      tandem mass spectrometry. Sulfophthalimides (SPI; 3 and 4) were identified as
      major metabolites by comparison with synthesized reference compounds. SPI was
      formed from both dyes in fungal cultures and by incubation with its purified
      manganese peroxidase and lignin peroxidase. Quantitative assessment of the SPI
      formed from RB15 accounted for approximately 60% of the theoretical amount.

PMID- 11583846
TI  - Difference in cholesterol-binding and cytolytic activities between listeriolysin
      O and seeligeriolysin O: a possible role of alanine residue in tryptophan-rich
      undecapeptide.
AB  - We have constructed recombinant listeriolysin O (rLLO) and seeligeriolysin O
      (rLSO) from Listeria monocytogenes and Listeria seeligeri, respectively. In
      hemolysis and cholesterol-binding assays, the specific activity of recombinant
      toxin was lower for LSO as compared to LLO. To understand the molecular basis of
      this difference, in particular with respect to the conserved Trp-rich
      undecapeptide, a naturally occurring Ala to Phe substitution in LSO was
      introduced into rLLO. The rLLO:A488F hemolysin exhibited a reduced activity in
      both hemolysis and cholesterol-binding. The reverse mutation, inserted into rLSO,
      also increased the hemolytic activity of this mutant LSO. These results suggested
      that the natural replacement of Ala to Phe is involved in the weak cytolytic
      activity of LSO.

PMID- 11583847
TI  - An unusual beta-ketoacyl:acyl carrier protein synthase and acyltransferase motifs
      in TaK, a putative protein required for biosynthesis of the antibiotic TA in
      Myxococcus xanthus.
AB  - The antibiotic TA of Myxococcus xanthus is produced by a type-I polyketide
      synthase mechanism. Previous studies have indicated that TA genes are clustered
      within a 36-kb region. The chemical structure of TA indicates the need for
      several post-modification steps, which are introduced to form the final bioactive
      molecule. These include three C-methylations, an O-methylation and a specific
      hydroxylation. In this study, we describe the genetic analysis of taK, encoding a
      specific polyketide beta-ketoacyl:acyl carrier protein synthase, which contains
      an unusual beta-ketoacyl synthase and acyltransferase motifs and is likely to be
      involved in antibiotic TA post-modification. Functional analysis of this beta
      ketoacyl:acyl carrier protein synthase by specific gene disruption suggests that
      it is essential for the production of an active TA molecule.

PMID- 11583848
TI  - An enteroaggregative Escherichia coli strain of serotype O111:H12 damages and
      invades cultured T84 cells and human colonic mucosa.
AB  - The pathogenic mechanisms of enteroaggregative Escherichia coli (EAEC) are not
      well defined. We investigated the interaction of EAEC strain 236 (serotype
      O111:H12) with polarised Caco-2 and T84 human intestinal epithelial cells lines,
      and with human jejunal and colonic mucosa. Strain 236 adhered to both polarised
      cell lines and to both intestinal tissue types, but caused severe damage and was
      invasive only in T84 cells and colonic mucosa. In contrast, prototype EAEC strain
      042, which also adhered to the cultured intestinal cell lines, did not adhere to
      or invade jejunal or colonic tissue. These observations suggest a heterogeneity
      of virulence properties within the EAEC category of diarrhoea-causing E. coli.

PMID- 11583849
TI  - Role of Cys54 in AbrB multimerization and DNA-binding activity.
AB  - The DNA-binding, global regulatory protein AbrB from Bacillus subtilis is
      homotetrameric in solution. Mutation of the lone cysteine present in the
      protomers (C54), to either a serine, tyrosine or tryptophan, abolishes DNA
      binding activity in vitro and regulatory activity in vivo. The effect of these
      changes is not due to abrogation of disulfide bond formation since it can be
      shown biochemically that none of the C54 residues participates in disulfide bond
      formation. It is unlikely that C54 is involved in direct contact with DNA
      targets. Rather, it appears that the role of C54 is to provide a nucleophilic
      center required for proper spatial orientation of the polypeptide subunits.

PMID- 11583850
TI  - Salicylate uniquely induces a 27-kDa protein in tubercle bacillus.
AB  - Salicylate was found to uniquely induce a 27-kDa protein in Mycobacterium
      tuberculosis complex organisms but not in Mycobacterium smegmatis or Escherichia
      coli. The structural analogue antitubercular para-amino-salicylate also induced
      the 27-kDa protein but to a somewhat lower level than salicylate. Other
      structural analogues such as benzoic acid and acetyl salicylic acid (aspirin) did
      not induce the 27-kDa protein. Western blot analysis indicated that the 27-kDa
      protein was localized mainly in the cytoplasm. The 27-kDa protein was not
      expressed at different growth phases in the absence of salicylate. The 27-kDa
      protein was identified as a putative benzoquinone methyltransferase (Rv0560c),
      which has several homologues in the M. tuberculosis genome. The cloned 27-kDa
      gene was found to express constitutively in E. coli, M. smegmatis and BCG with or
      without salicylate.

PMID- 11583851
TI  - Characterization of three bioenergetically active respiratory terminal oxidases
      in the cyanobacterium Synechocystis sp. strain PCC 6803.
AB  - Synechocystis sp. PCC 6803 contains three respiratory terminal oxidases (RTOs):
      cytochrome c oxidase (Cox), quinol oxidase (Cyd), and alternate RTO (ARTO).
      Mutants lacking combinations of the RTOs were used to characterize these key
      enzymes of respiration. Pentachlorophenol and 2-heptyl-4-hydroxy-quinoline-N
      oxide inhibited Cyd completely, but had little effect on electron transport to
      the other RTOs. KCN inhibited all three RTOs but the in vivo K(I) for Cox and Cyd
      was quite different (7 vs. 27 microM), as was their affinity for oxygen (K(M) 1.0
      vs. 0.35 microM). ARTO has a very low respiratory activity. However, when uptake
      of 3-O-methylglucose, an active H+ co-transport, was used to monitor energization
      of the cytoplasmic membrane, ARTO was similarly effective as the other RTOs. As
      removal of the gene for cytochrome c(553) had the same effects as removal of ARTO
      genes, we propose that the ARTO might be a second Cox. The possible functions,
      localization and regulation of the RTOs are discussed.

PMID- 11583852
TI  - Saccharomyces cerevisiae pyruvate kinase Pyk1 is PKA phosphorylation substrate in
      vitro.
AB  - Fractionation of Saccharomyces cerevisiae postribosomal extract on DEAE-cellulose
      revealed two fractions of cAMP-dependent protein kinase (PKA-1 and PKA-2). The
      presence of PKA in both fractions was confirmed by immunoblotting with anti-Bcy1
      antibodies. Yeast pyruvate kinase Pyk1 identified by amino acid microsequencing
      analysis and immunoblotting with anti-Pyk1 antibodies copurified with the PKA-1
      but not the -2 fraction. Pyk1 can be phosphorylated by yeast PKA in vitro in the
      presence of cAMP and cGMP. Two-dimensional gel electrophoretic analysis revealed
      four phosphorylated forms of Pyk1 modified by PKA. In phosphorylation of Pyk1
      mainly the Tpk2 catalytic subunit of yeast PKA was involved.

PMID- 11583853
TI  - The role of glucose in the Kluyveromyces bulgaricus flocculation phenomenon:
      transduction by cAMP-dependent protein kinase pathway?
AB  - Yeast flocculation appears to be dependent on several culture conditions such as
      nitrogen or carbon sources. In 0.2% glucose medium Kluyveromyces bulgaricus
      flocculation intensity is weak (10% at maximum) by comparison with flocculation
      in 2% glucose medium (85% maximum). Addition of glucose to K. bulgaricus in
      exponential growth phase in 0.2% glucose medium produced a rapid increase of the
      flocculation percentage during the 30 min following the addition of glucose. cAMP
      and 2,4-dinitrophenol showed similar effects while cAMP-dependent protein kinase
      (PKA) inhibitors exhibited an antagonist effect. Moreover, the induction of
      flocculation did not seem to imply translation of new proteins: cycloheximide had
      no effect, although growth was inhibited. The induction of flocculation mainly
      implies ATP hydrolysis for activation or secretion of galactose-specific
      receptors as demonstrated by treatment with NaN(3). We propose a hypothesis that
      involves a PKA transduction signal leading to flocculation.

PMID- 11583854
TI  - Na+-driven multidrug efflux pump VcmA from Vibrio cholerae non-O1, a non
      halophilic bacterium.
AB  - A chromosomal DNA fragment from Vibrio cholerae non-O1 containing a drug
      resistance determinant was cloned and sequenced. The deduced amino acid sequence
      suggested that the determinant gene encodes a multidrug efflux pump. We
      designated the pump VcmA. Escherichia coli cells transformed with a plasmid
      carrying the vcmA gene showed increased resistance against norfloxacin,
      ciprofloxacin, ofloxacin, daunomycin, doxorubicin, streptomycin, kanamycin,
      ethidium bromide, 4',6-diamidino-2-phenylindole dihydrochloride, Hoechst 33342
      and acriflavine. Na+ (or Li+)-dependent efflux of ethidium bromide was detected
      in transformant cells. Efflux of Na+, elicited by ethidium bromide, was observed
      from transformant cells. Thus, we concluded that the VcmA is a Na+/drug
      antiporter.

PMID- 11583855
TI  - Characterization of a hypervariable region in the genome of Chlamydophila
      pneumoniae.
AB  - Chlamydophila pneumoniae displays surprisingly little genomic variation, as seen
      by comparisons of the published genomes from three different isolates and
      sequencing of four different genes from different isolates. We have in the
      present study, however, demonstrated genomic variation between 10 C. pneumoniae
      isolates in the 11690-bp region between the two outer membrane protein genes pmp1
      and pmp2. This region of the C. pneumoniae CWL-029 isolate contains seven C.
      pneumoniae-specific open reading frames (hb1-7, encoding hydrophobic beta-sheet
      containing proteins). We identified additionally 12 open reading frames in the C.
      pneumoniae CWL-029 genome encoding hypothetical proteins with similarity to the
      seven hypothetical Hb-proteins. Compared to other isolates, genomic variation is
      seen to cause frame-shifting of three of the 19 hb-open reading frames, which are
      proposed to be three full-length genes and eight frame-shifted pseudogenes. The
      hypothetical proteins encoded by these proposed genes contain an N-terminally
      located highly hydrophobic stretch of 50-60 residues. A similar motif is found in
      all identified Chlamydia inclusion membrane proteins and therefore the Hb
      proteins are candidate inclusion proteins.

PMID- 11583856
TI  - Identification of Trichoderma strains by image analysis of HPLC chromatograms.
AB  - Forty-four Trichoderma strains from water-damaged building materials or indoor
      dust were classified with chromatographic image analysis on full chromatographic
      matrices obtained by high performance liquid chromatography with UV detection of
      culture extracts. The classes were compared with morphological identification and
      rDNA sequence data, and for each class all strains were of the same identity.
      With all three techniques each strain--except one--was identified as the same
      species. These strains belonged to Trichoderma atroviride (nine strains),
      Trichoderma viride (three strains), Trichoderma harzianum (10 strains),
      Trichoderma citrinoviride (12 strains), and Trichoderma longibrachiatum (nine
      strains). The odd strain was identified as Trichoderma hamatum by morphology and
      rDNA sequencing, but not by image analysis as no reference strains of this
      species were included. It is concluded that the secondary metabolite profile
      contains sufficient information for classification and species identification.

PMID- 11583857
TI  - Purification and characterization of a glutathione S-transferase from the fungus
      Cunninghamella elegans.
AB  - Cunninghamella elegans grown on Sabouraud dextrose broth had glutathione S
      transferase (GST) activity. The enzyme was purified 172-fold from the cytosolic
      fraction (120000 x g) of the extract from a culture of C. elegans, using Q
      Sepharose ion exchange chromatography and glutathione affinity chromatography.
      The GST showed activity against 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4
      nitrobenzene, 4-nitrobenzyl chloride, and ethacrynic acid. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis gel filtration chromatography revealed that
      the native enzyme was homodimeric with a subunit of M(r) 27000. Comparison by
      Western blot analysis implied that this fungal GST had no relationship with
      mammalian alpha-, mu-, and pi-class GSTs, although it showed a small degree of
      cross-reactivity with a theta-class GST. The N-terminal amino acid sequence of
      the purified enzyme showed no significant homology with other known GSTs.

PMID- 11583858
TI  - Characterization of biofilm growth and biocide susceptibility testing of
      Mycobacterium phlei using the MBEC assay system.
AB  - The importance of non-tuberculosis mycobacterial biofilm species in medicine,
      industry and the environment has recently gained attention. Our objectives were
      to characterize biofilm growth of Mycobacterium phlei M4, as a model of rapidly
      growing mycobacteria using the minimal biofilm eradication concentration (MBEC)
      and to compare biocide susceptibility of planktonic and biofilm organisms.
      Scanning electron microscopy was also carried out to observe biofilm morphology.
      With the exception of Sporicidin and Virkon the minimum bactericidal
      concentration values for all biocides tested were lower than the MBEC values. The
      MBEC assay system was seen to produce multiple and reproducible biofilms of M.
      phlei and to be a useful tool for susceptibility studies.

PMID- 11583859
TI  - Secretion of the rotavirus VP8* protein in Lactococcus lactis.
AB  - Secretion of the VP8* subunit of the VP4 capsid protein of rotavirus by
      Lactococcus lactis has been achieved. For this purpose, a secretion vector has
      been constructed with the lactococcal signal sequence AL9 and the VP8*-encoding
      gene fragment. The amount of VP8* secreted by L. lactis in the culture
      supernatant was quantified and visualised by Western blot. Furthermore, it was
      shown to retain its hemagglutination capability, indicating that the conformation
      of the secreted peptide may be retaining its biological activity.

PMID- 11583860
TI  - The evolving management of acute right-sided heart failure in cardiac transplant
      recipients.
AB  - Avoidance of the clinical syndrome of acute right-sided heart failure after heart
      transplantation is, unfortunately, not possible. Clinical experience and the
      literature certainly suggest that a significant factor in the successful
      management of right ventricular (RV) failure is recipient selection. Moreover,
      threshold hemodynamic values beyond which RV failure is certain to occur and
      heart transplantation is contraindicated do not exist. Nor are there values below
      which RV failure is always avoidable. Acute RV failure will remain a difficult
      and ever-present clinical syndrome in the transplant recipient. Goals in the
      treatment of this clinical problem include: 1. Preserving coronary perfusion
      through maintenance of systemic blood pressure. 2. Optimizing RV preload. 3.
      Reducing RV afterload by decreasing pulmonary vascular resistance (PVR). 4.
      Limiting pulmonary vasoconstriction through ventilation with high inspired oxygen
      concentrations (100% FiO(2)), increased tidal volume and optimal positive end
      expiratory pressure ventilation. Inhaled nitric oxide is recommended before
      leaving the operating room in cases where the initial therapies have had little
      impact. Intra-aortic balloon counterpulsation is employed in patients with
      impaired left ventricular (LV) function and may be of benefit in patients with RV
      dysfunction resulting from ischemia, preservation injury or reperfusion injury.
      Optimal LV function reduces RV afterload and PVR. A proactive decision regarding
      RV assist device implantation is made before leaving the operating room and is
      highly dependent upon overall hemodynamics, size and function of the ventricles
      as seen on transesophageal echocardiography, renal function and surgical
      bleeding. Only through careful preoperative planning can this life-threatening
      condition be managed in the postoperative period.

PMID- 11583861
TI  - Metoprolol controlled release/extended release in patients with severe heart
      failure: analysis of the experience in the MERIT-HF study.
AB  - OBJECTIVES: This study analyzed the effect of the beta(1)-selective beta-blocker
      metoprolol succinate controlled release/extended release (CR/XL) once daily on
      mortality, hospitalizations and tolerability in patients with severe heart
      failure. BACKGROUND: There continues to be resistance to the incorporation of
      beta-blockers into clinical care, largely due to concerns about their benefit in
      patients with more severe heart failure. METHOD: SA subgroup of patients from
      Metoprolol CR/XL Randomized Intervention Trial in chronic Heart Failure (MERIT
      HF) in New York Heart Association (NYHA) functional class III/IV with left
      ventricular ejection fraction < 0.25 were identified (n = 795). The analysis was
      by intention-to-treat. RESULTS: The mean ejection fraction at baseline was 0.19,
      and the yearly placebo mortality during follow-up was 19.1%. Treatment with
      metoprolol CR/XL compared to placebo resulted in significant reductions in all
      predefined mortality end points including: total mortality, 45 versus 72 deaths
      (risk reduction 39%; 95% confidence interval 11% to 58%; p = 0.0086); sudden
      death, 22 vs. 39 deaths (45% [7% to 67%]; p = 0.024); and death due to worsening
      heart failure, 13 vs. 28 deaths (55% [13% to 77%]; p = 0.015). Metoprolol CR/XL
      also reduced the number of hospitalizations for worsening heart failure by 45%
      compared with placebo (p < 0.0001). The NYHA functional class improved in the
      metoprolol CR/XL group compared with placebo (p = 0.0031). Metoprolol CR/XL was
      well tolerated, with 31% fewer patients withdrawn from study medicine (all
      causes) compared with placebo (p = 0.027). CONCLUSIONS: This subgroup analysis of
      the MERIT-HF study shows that patients with severe heart failure receive a
      similar mortality benefit and a similar reduction in hospitalizations for
      worsening heart failure with metoprolol CR/XL treatment as those patients
      included in the total study.

PMID- 11583862
TI  - Prospective crossover comparison of carvedilol and metoprolol in patients with
      chronic heart failure.
AB  - OBJECTIVES: This study investigates the effects of a change of beta-adrenergic
      blocking agent treatment from metoprolol to carvedilol and vice versa in patients
      with heart failure (HF). BACKGROUND: Beta-blockers improve ventricular function
      and prolong survival in patients with HF. It has recently been suggested that
      carvedilol has more pronounced effects on left ventricular ejection fraction
      (LVEF) compared with metoprolol. It is uncertain whether a change from one beta
      blocker to the other is safe and leads to any change of left ventricular
      function. METHODS: Forty-four patients with HF due to ischemic (n = 17) or
      idiopathic cardiomyopathy (n = 27) that had responded well to long-term treatment
      with either metoprolol (n = 20) or carvedilol (n = 24) were switched to an
      equivalent dose of the respective other beta-blocker. Before and six months after
      crossover of treatment, echocardiography, radionuclide ventriculography and
      dobutamine stress echocardiography were performed. RESULTS: Six months after
      crossover of beta-blocker treatment, LVEF had further improved with both
      carvedilol and metoprolol (carvedilol: 32 +/- 3% to 36 +/- 4%; metoprolol: 27 +/-
      4% to 30 +/- 5%; both p < 0.05 vs. baseline), without interindividual
      differences. There were no changes in either New York Heart Association
      functional class or any other hemodynamic parameters at rest. Dobutamine stress
      echocardiography revealed a more pronounced increase of heart rate after
      dobutamine infusion in metoprolol- compared with carvedilol-treated patients.
      After dobutamine infusion, LVEF increased in the carvedilol- but not in the
      metoprolol-treated group. CONCLUSIONS: When switching treatment from one beta
      blocker to the other, improvement of LVEF in patients with HF is maintained.
      Despite similar long-term effects on hemodynamics at rest, beta-adrenergic
      responsiveness is different in both treatments.

PMID- 11583863
TI  - Oxidative capacity of skeletal muscle in heart failure patients versus sedentary
      or active control subjects.
AB  - OBJECTIVES: We investigated the in situ properties of muscle mitochondria using
      the skinned fiber technique in patients with chronic heart failure (CHF) and
      sedentary (SED) and more active (ACT) controls to determine: 1) whether
      respiration of muscle tissue in the SED and ACT groups correlates with peak
      oxygen consumption (pVO(2)), 2) whether it is altered in CHF, and 3) whether this
      results from deconditioning or CHF-specific myopathy. BACKGROUND: Skeletal muscle
      oxidative capacity is thought to partly determine the exercise capacity in humans
      and its decrease to participate in exercise limitation in CHF. METHODS: M. Vastus
      lateralis biopsies were obtained from 11 SED group members, 10 ACT group members
      and 15 patients with CHF at the time of transplantation, saponine-skinned and
      placed in an oxygraphic chamber to measure basal and maximal adenosine
      diphosphate (ADP)-stimulated (V(max)) respiration rates and to assess
      mitochondrial regulation by ADP. All patients received angiotensin-converting
      enzyme (ACE) inhibitors. RESULTS: The pVO(2) differed in the order CHF < SED <
      ACT. Compared with SED, muscle alterations in CHF appeared as decreased citrate
      synthase, creatine kinase and lactate dehydrogenase, whereas the myosin heavy
      chain profile remained unchanged. However, muscle oxidative capacity (V(max),
      CHF: 3.53 +/- 0.38; SED: 3.17 +/- 0.48; ACT: 7.47 +/- 0.73, micromol O(2).min(
      1).g(-1)dw, p < 0.001 vs. CHF and SED) and regulation were identical in patients
      in the CHF and SED groups, differing in the ACT group only. In patients with CHF,
      the correlation between pVO(2) and muscle oxidative capacity observed in controls
      was displaced toward lower pVO(2) values. CONCLUSIONS: In these patients, the
      disease-specific muscle metabolic impairments derive mostly from
      extramitochondrial mechanisms that disrupt the normal symmorphosis relations. The
      possible roles of ACE inhibitors and level of activity are discussed.

PMID- 11583864
TI  - Reduced kidney function and anemia as risk factors for mortality in patients with
      left ventricular dysfunction.
AB  - OBJECTIVES: We sought to evaluate the relationship between the level of kidney
      function, level of hematocrit and their interaction on all-cause mortality in
      patients with left ventricular (LV) dysfunction. BACKGROUND: Anemia and reduced
      kidney function occur frequently in patients with heart failure. The level of
      hematocrit and its relationship with renal function have not been evaluated as
      risk factors for mortality in patients with LV dysfunction. METHODS: We
      retrospectively examined the Studies Of LV Dysfunction (SOLVD) database.
      Glomerular filtration rate (GFR) was predicted using a recently validated
      formula. Kaplan-Meier survival analyses were used to compare survival times
      between groups stratified by level of kidney function (predicted GFR) and
      hematocrit. Cox proportional-hazards regression was used to explore the
      relationship of survival time to level of kidney function, hematocrit and their
      interaction. RESULTS: Lower GFR and hematocrit were associated with a higher
      prevalence of traditional cardiovascular risk factors. In univariate analysis,
      reduced kidney function and lower hematocrit, in men and in women, were risk
      factors for all-cause mortality (p < 0.001 for both). After adjustment for other
      factors significant in univariate analysis, a 10 ml/min/1.73 m(2) lower GFR and a
      1% lower hematocrit were associated with a 1.064 (95% CI: 1.033, 1.096) and 1.027
      (95% CI: 1.015, 1.038) higher risk for mortality, respectively. At lower GFR and
      lower hematocrit, the risk was higher (p = 0.022 for the interaction) than that
      predicted by both factors independently. CONCLUSIONS: Decreased kidney function
      and anemia are risk factors for all-cause mortality in patients with LV
      dysfunction, especially when both are present. These relationships need to be
      confirmed in additional studies.

PMID- 11583865
TI  - Circulatory response to fluid overload removal by extracorporeal ultrafiltration
      in refractory congestive heart failure.
AB  - OBJECTIVES: The goal of this study was to investigate the hemodynamic and
      circulatory adjustments to extracorporeal ultrafiltration (UF) in refractory
      congestive heart failure (rCHF). BACKGROUND: In rCHF, UF allows clinical
      improvement and restores diuretic efficacy. However, in the course of a UF
      session, patients are exposed to rapid variations of body fluid composition so
      that, as fluid is withdrawn from the intravascular compartment, hypotension or
      even shock could occur. METHODS: In 24 patients with rCHF undergoing UF, we
      measured, after every liter of plasma water removed, hemodynamics, blood gas
      analysis (in both systemic and pulmonary arteries), plasma volume changes (PV)
      and plasma refilling rate (PRR). The PV and PRR were calculated by considering
      hematocrit and ultrafiltrate volume. RESULTS: In all patients, UF was performed
      safely, without side effects or hemodynamic instability (ultrafiltrate = 4,880 +/
      896 ml). Mean right atrial, pulmonary artery and wedge pressures progressively
      reduced during the procedure. Cardiac output increased at the end of the
      procedure and, to a greater extent, 24 h later, in relation to the increase of
      stroke volume. Heart rate and systemic vascular resistance did not increase, and
      other peripheral biochemical parameters did not worsen during UF. Intravascular
      volume remained stable throughout the entire duration of the procedure,
      indicating that a proportional volume of fluid was refilled from the congested
      parenchyma. CONCLUSIONS: In patients with rCHF, subtraction of plasma water by UF
      is associated with hemodynamic improvement. Fluid refilling from the overhydrated
      interstitium is the major compensatory mechanism for intravascular fluid removal,
      and hypotension does not occur when plasma refilling rate is adequate to prevent
      hypovolemia.

PMID- 11583866
TI  - Use of risk stratification to identify patients with unstable angina likeliest to
      benefit from an invasive versus conservative management strategy.
AB  - OBJECTIVES: This study was designed to determine whether patient characteristics
      collected at presentation can identify which patients benefit from immediate
      coronary angiography and revascularization. BACKGROUND: Risk stratification may
      offer a method for identifying which patients with unstable angina or non-Q-wave
      myocardial infarction (NQMI) are likeliest to benefit from invasive management
      strategies. METHODS: The analysis was based on data from a randomized controlled
      trial that enrolled 1,473 patients presenting with unstable angina or NQMI who
      were randomly assigned to an early invasive or early conservative (medical)
      management strategy. We constructed a risk-stratification score for each patient
      based on adjusted odds ratios for clinical variables likely to predict adverse
      outcomes. We stratified all trial subjects by their risk scores and studied the
      rates of death or myocardial infarction (MI) of the early invasive management
      strategy in each stratum. RESULTS: The final multivariate model included older
      age, ST segment depression on presentation, history of complicated angina before
      presentation, and elevation in baseline creatine kinase-MB fraction. Although
      patients with a higher risk score had an increased rate of death or MI within 42
      days and 365 days (p < 0.001) in both management strategies, early invasive
      management for patients in the high and very high risk categories was associated
      with a lower rate of death or MI within 42 days compared with conservative
      management. No such benefit was seen in patients in the larger group of patients
      in the very low, low or moderate risk categories (p = 0.03 for the interaction
      between risk category and management assignment). CONCLUSIONS: Risk
      stratification may be an effective method for identifying those patients with
      unstable angina or NQMI most likely to benefit from early invasive management.
      Selective use of early invasive management can have a substantial impact in
      reducing morbidity and mortality in higher risk patients, but may not be
      warranted in lower risk patients.

PMID- 11583867
TI  - Should we catheterize all patients with unstable angina? No--only the ones with
      coronary artery disease.

PMID- 11583868
TI  - Mechanisms behind the prognostic value of troponin T in unstable coronary artery
      disease: a FRISC II substudy.
AB  - OBJECTIVES: This study was designed to elucidate possible mechanisms for the
      prognostic value of troponin T (tnT). BACKGROUND: The reasons for the adverse
      prognosis associated with elevation of troponins in unstable coronary artery
      disease are poorly understood. METHODS: Patients enrolled in the Fast
      Revascularization during InStability in CAD (FRISC-II) trial were included.
      Clinical characteristics, findings at echocardiography and coronary angiography,
      and prognosis were evaluated in relation to different tnT levels. RESULTS:
      Absence of significant coronary stenosis was more frequent and three-vessel
      disease or left main stem stenosis was less frequent in patients without,
      compared with, detectable tnT. The occurrence of visible thrombus increased with
      rising levels of tnT. In the group with the highest levels of tnT, occlusion of
      the left circumflex artery was more common than in the three other tnT groups, as
      was a left ventricular ejection fraction below 0.45. The one-year risk of death
      in the noninvasive arm of the study increased by increasing levels of tnT (1.6%
      to 4.6%), whereas the risk of myocardial infarction showed an inverted U-shaped
      curve and was lower in the lowest (5.5%) and highest (8.4%) tnT groups than in
      the two intermediate groups (17.5% and 16.2%). CONCLUSIONS: Any detectable
      elevation of tnT raises the probability of significant coronary stenosis and
      thrombus formation and is associated with an increased risk of reinfarction and
      death. However, at a more pronounced elevation of troponin, a higher proportion
      of patients has a persistent occlusion of the culprit vessel and reduced left
      ventricular function, associated with a high mortality but a modest risk of
      reinfarction.

PMID- 11583869
TI  - Troponin measurements in ischemic heart disease: more than just a black and white
      picture.

PMID- 11583870
TI  - Prognostic value of serum cardiac troponin I in ambulatory patients with chronic
      renal failure undergoing long-term hemodialysis: a two-year outcome analysis.
AB  - OBJECTIVES: We sought to evaluate the prognostic value of cardiac troponin I
      (cTnI) in asymptomatic, ambulatory patients with chronic renal failure treated
      with long-term hemodialysis. BACKGROUND: Smaller, short-term follow-up studies on
      this subject have given conflicting results. METHODS: A total of 126 ambulatory
      patients with chronic renal failure treated with long-term hemodialysis were
      followed for two years for all-cause mortality, cardiac mortality, all-cause
      hospital admissions and cardiac hospital admissions. Serum cTnI was measured
      before dialysis at the time of study entry. RESULTS: One hundred two patients had
      normal serum levels of cTnI (< or =0.03 ng/ml) and 24 patients had elevated
      levels (0.015 +/- 0.007 vs. 0.053 +/- 0.029 ng/ml, p < 0.0001). No significant
      difference in all-cause mortality (20 vs. 4 deaths), cardiac mortality (4 vs. 1
      death), all-cause hospital admissions (1.74 +/- 1.72 vs. 1.25 +/- 1.19
      admissions/patient) or cardiac admissions (0.52 +/- 0.89 vs. 0.33 +/- 0.76
      admissions/patient) was present between the patients with normal cTnI levels and
      those with elevated cTnI levels. Serum cTnI was not significantly different
      between patients who died versus those who survived (0.022 +/- 0.019 vs. 0.022 +/
      0.021 ng/ml). Serum cTnI was not an independent predictor of all-cause
      mortality, cardiac mortality, all-cause admissions or cardiac admissions. Age
      (older) and serum albumin (lower) were independent predictors of all-cause
      mortality, whereas a history of myocardial infarction was an independent
      predictor of cardiac mortality. Serum sodium (lower) was an independent predictor
      of all-cause hospital admissions, whereas hypertension and previous myocardial
      infarction were independent predictors of cardiac admissions. The best predictors
      of the time to death were age (older) and serum sodium level (lower),
      irrespective of the serum cTnI levels. CONCLUSIONS: Cardiac troponin I has a
      limited role in predicting mortality and hospital admissions in asymptomatic
      patients with chronic renal failure treated with long-term hemodialysis.

PMID- 11583871
TI  - Testing the wrong hypothesis: the failure to recognize the limitations of
      troponin assays.

PMID- 11583872
TI  - Circulating monocyte-platelet aggregates are an early marker of acute myocardial
      infarction.
AB  - OBJECTIVES: We investigated whether elevated levels of circulating monocyte
      platelet aggregates (MPA) can be used to identify patients with acute myocardial
      infarction (AMI). BACKGROUND: Commonly used blood markers of AMI reflect
      myocardial cell death, but do not reflect the earlier pathophysiologic processes
      of plaque rupture, platelet activation and resultant thrombus formation.
      Circulating MPA form after platelet activation. METHODS: In a single center
      between October 1998 and November 1999, we measured circulating MPA in a blinded
      fashion by whole blood flow cytometry in 211 consecutive patients who presented
      to the emergency department (ED) with chest pain and were admitted to rule out
      AMI. Acute myocardial infarction was diagnosed by a CK-MB fraction greater than
      three times control. RESULTS: Patients with AMI (n = 61), as compared with those
      without AMI (n = 150), had significantly higher numbers of circulating MPA (11.6
      +/- 11.4 vs. 6.4 +/- 3.6, mean +/- SD, p < 0.0001). After controlling for age,
      the adjusted odds of developing AMI for patients in the 2nd, 3rd and 4th
      quartiles of MPA, in comparison with patients in the lowest quartile (odds ratio
      = 1.0), were 2.1 (95% confidence interval [CI]: 0.7, 6.8), 4.4 (95% CI: 1.5,
      13.1) and 10.8 (95% CI: 3.6, 32.0), respectively. The number of circulating MPA
      in patients with AMI presenting within 4 h of symptom onset (14.4) was
      significantly greater than those presenting after 4 h (9.4) and after 8 h (7.0),
      (p < 0.001). Of the 61 patients with AMI, 35 (57%) had a normal creatine kinase
      isoenzyme ratio at the time of presentation to the ED, but had high levels of
      circulating MPA (13.3). CONCLUSIONS: Circulating MPA are an early marker of AMI.

PMID- 11583873
TI  - Diabetes mellitus prevents ischemic preconditioning in patients with a first
      acute anterior wall myocardial infarction.
AB  - OBJECTIVES: This study was undertaken to assess whether prodromal angina could
      have beneficial effects in diabetic patients with acute myocardial infarction
      (AMI). BACKGROUND: Prodromal angina occurring shortly before the onset of AMI is
      associated with favorable outcomes by the mechanism of ischemic preconditioning.
      However, little is known about the impact of diabetes on ischemic
      preconditioning. METHODS: We studied 611 patients with a first anterior wall AMI
      who underwent emergency catheterization within 12 h after the onset of chest
      pain: 490 patients without diabetes and 121 patients with non-insulin treated
      diabetes. Prodromal angina was defined as angina episode(s) occurring within 24 h
      before the onset of AMI. Serial contrast left ventriculograms were obtained in
      424 patients at the time of acute and predischarge catheterization. RESULTS: In
      non-diabetic patients, prodromal angina was associated with lower peak creatine
      kinase (CK) value (3,068 +/- 2,647 IU/l vs. 3,601 +/- 2,462 IU/l, p = 0.037),
      larger increase in left ventricular ejection fraction (LVEF) (10.1 +/- 13.0% vs.
      5.8 +/- 13.4%, p = 0.004) and lower in-hospital mortality (3.4% vs. 9.3%, p =
      0.015). On the contrary, in diabetic patients, there was no significant
      difference in peak CK value (3,382 +/- 2,520 IU/l vs. 3,233 +/- 2,412 IU/l, p =
      NS), the change in LVEF (6.7 +/- 13.8% vs. 7.1 +/- 12.4%, p = NS) and in-hospital
      mortality (8.8% vs. 11.0%, p = NS) between patients with and patients without
      prodromal angina. CONCLUSIONS: Prodromal angina limited infarct size, enhanced
      recovery of LV function and improved survival in non-diabetic patients with AMI.
      However, such beneficial effects of prodromal angina were not observed in
      diabetic patients, suggesting that diabetes might prevent ischemic
      preconditioning.

PMID- 11583874
TI  - The effect of risk factor reductions between 1981 and 1990 on coronary heart
      disease incidence, prevalence, mortality and cost.
AB  - OBJECTIVES: We sought to estimate the impact and cost-effectiveness of risk
      factor reductions between 1981 and 1990. BACKGROUND: Coronary heart disease (CHD)
      mortality rates have declined dramatically, partly as a result of reductions in
      CHD risk factors. METHODS: We used the CHD Policy Model, a validated computer
      simulation model, to estimate the effects of actual investments made to change
      coronary risk factors between 1981 and 1990, as well as the impact of these
      changes on the incidence, prevalence, mortality and costs of CHD during this
      period and projected to 2015. RESULTS: Observed changes in risk factors between
      1981 and 1990 resulted in a reduction of CHD deaths by approximately 430,000 and
      overall deaths by approximately 740,000, with an estimated cost-effectiveness of
      about $44,000 per year of life saved during this period, based on the estimated
      actual costs of the interventions used. However, because much of the benefit of
      risk factor reductions is delayed, the estimated reductions for the 35-year
      period of 1981 to 2015 were 3.6 million CHD deaths and 1.2 million non-CHD
      deaths, at a cost of only about $5,400 per year of life saved. CONCLUSIONS:
      Aggregate efforts to reduce risk factors between 1981 and 1990 have led to
      substantial reductions in CHD and should be well worth the cost, largely because
      of population-wide changes in life-style and habits. Some interventions are much
      better investments than others, and attention to such issues could lead to better
      use of resources and better outcomes in the future.

PMID- 11583875
TI  - Major risk factors and coronary heart disease: much has been achieved but crucial
      challenges remain.

PMID- 11583876
TI  - Role of Kozak sequence polymorphism of platelet glycoprotein Ibalpha as a risk
      factor for coronary artery disease and catheter interventions.
AB  - OBJECTIVES: We sought to determine the role of the -5T/C polymorphism of the
      platelet glycoprotein (GP) Ibalpha as a potential risk factor for coronary artery
      disease (CAD) and adverse events complicating a coronary catheter intervention.
      BACKGROUND: The platelet GP Ib-IX-V receptor complex plays a crucial role in
      arterial thrombus formation. The -5T/C polymorphism of GP Ibalpha is associated
      with increased receptor density. METHODS: We genotyped 1,000 patients with
      angiographically confirmed CAD, as well as 1,000 age- and gender-matched control
      subjects, for this polymorphism by polymerase chain reaction/restriction fragment
      length polymorphism. Among the patients with CAD, 269 underwent percutaneous
      transluminal coronary angioplasty (PTCA), 103 underwent directional coronary
      atherectomy and 278 underwent stenting. This intervention group was followed for
      a 30-day composite end point of target vessel revascularization, myocardial
      infarction or death. RESULTS: Carriers of the -5C allele were significantly over
      represented in the group of patients developing acute coronary syndromes
      (relative risk [RR] 1.43, 95% confidence interval [CI] 1.05 to 1.95, p = 0.02).
      The -5C allele furthermore predicted an increased risk for developing
      complications after PTCA (RR 3.75, 95% CI 1.15 to 12.27, p = 0.029). CONCLUSIONS:
      The -5C allele of the GP Ibalpha Kozak polymorphism may represent a risk factor
      in clinical conditions in which thrombosis plays an important role, such as in
      acute coronary syndromes and in complications after PTCA.

PMID- 11583877
TI  - Platelet polymorphisms and ischemic heart disease: moving beyond traditional risk
      factors.

PMID- 11583878
TI  - Variability of myocardial perfusion defects assessed by thallium-201 scintigraphy
      in patients with coronary artery disease not amenable to angioplasty or bypass
      surgery.
AB  - OBJECTIVES: We sought to assess the variability of results obtained with thallium
      scintigraphy as a method for tracking the extent of myocardial ischemia in
      medically refractory patients with angina who are not suitable for coronary
      artery bypass graft surgery or percutaneous transluminal coronary angioplasty.
      BACKGROUND: New therapies are being evaluated for patients with "no option"
      angina in whom medical therapy has failed. Nuclear techniques, like thallium
      scintigraphy, are used in multicenter trials to evaluate whether such therapies
      improve myocardial perfusion. However, the variability of test results is unknown
      in this patient group in a multicenter study. METHODS: The Angina Treatments:
      Lasers And Normal Therapies In Comparison (ATLANTIC) study was a randomized trial
      of transmyocardial laser revascularization (n = 182). Patients underwent
      dipyridamole thallium stress tests at baseline and 3, 6 and 12 months after
      enrollment. The control group (n = 90) was treated with constant medical therapy
      during the study and is a relevant group to investigate test variability. Test
      variability over time was quantified by the mean absolute change in the
      percentage of reversible perfusion defects between baseline and follow-up.
      RESULTS: Baseline percent myocardium with ischemia averaged 17.0 +/- 13.7% and
      did not change during follow-up. However, variations in the percent myocardium
      with reversible perfusion defects over time amounted to an average of 6 to 8
      percentage points, or 43% to 55% of the baseline value. Only approximately 13% of
      this variability was attributable to variability in image reconstruction and
      analysis. CONCLUSIONS: As demonstrated in the ATLANTIC study, percent myocardial
      ischemia in control subjects receiving constant medical therapy varied in
      individual patients by an average of approximately 50%. This may limit the
      utility of thallium scintigraphy to detect improved myocardial perfusion over
      time in response to therapy.

PMID- 11583879
TI  - Preliminary results of endovascular abdominal aortic aneurysm exclusion with the
      AneuRx stent-graft.
AB  - OBJECTIVES: This study evaluated the clinical effectiveness of the Medtronic
      AneuRx stent-graft in patients with infrarenal abdominal aortic aneurysms (AAAs)
      who were treated in an endovascular suite. BACKGROUND: The use of endovascular
      stent-graft prosthesis for the treatment of AAAs is receiving increasing
      attention as an alternative to standard surgical repair. Endovascular treatment
      of AAAs offers the potential to avoid the significant morbidity and mortality
      associated with surgical repair. METHODS: In this series, 215 patients have
      undergone AAA exclusion with the AneuRx stent-graft. Six-month follow-up is
      available in 132 patients; one-year follow-up is available in 84 and two-year
      follow-up in 22. RESULTS: Of the patients, one hundred ninety-two (89%) were
      male; 87% had hypertension, and 58.6% were American Society of Anesthesiologists
      grade IV or higher. The procedural success was 99.5%; we were unable to place the
      device in one patient. There was no procedural or one-month mortality. There were
      no acute conversions to surgical repair. One patient had a non-Q-wave myocardial
      infarction 24 h after the procedure. Endoleaks were present in 82 patients (42%)
      at discharge, 15 patients (11.3%) at six months and 10 patients (11.9%) at one
      year. Twenty-two patients had a secondary procedure for endoleak repair of which
      three were conversions to surgical repair. Twelve late deaths have occurred, none
      due to device failure or AAA rupture. Mean hospital stay was 1.9 days.
      CONCLUSIONS: These results reveal that infrarenal AAAs can be safely and
      successfully treated in an endovascular suite with the AneuRx stent-graft.
      Further follow-up is needed to determine the long-term efficacy of endoluminal
      treatment to prevent rupture and death due to AAAs.

PMID- 11583880
TI  - Endovascular aneurysm repair with the AneuRx stent-graft is safe, but is it
      effective?

PMID- 11583881
TI  - The effect of intracoronary radiation for the treatment of recurrent in-stent
      restenosis in patients with chronic renal failure.
AB  - OBJECTIVES: This study was designed to analyze the in-hospital and six-month
      clinical and angiographic outcomes of patients with chronic renal failure (CRF)
      treated with intracoronary radiation for the prevention of recurrence of in-stent
      restenosis. BACKGROUND: Patients with CRF are at a higher risk than the general
      population for accelerated atherosclerotic cardiovascular disease and for
      restenosis after percutaneous coronary intervention. Previous studies have shown
      the effectiveness of both beta and gamma radiation in preventing recurrent
      restenosis in patients with in-stent restenosis. METHODS: We studied the in
      hospital and six-month clinical and angiographic outcomes of 118 patients with
      CRF and 481 consecutive patients without CRF who were treated with intracoronary
      radiation for the prevention of recurrence of in-stent restenosis in native
      coronaries and saphenous vein grafts. RESULTS: Patients with CRF were usually
      older, women, hypertensive and diabetic, with multivessel disease and with
      reduced left ventricular function. In-hospital outcome for patients with CRF was
      marred by a higher incidence of death, non-Q-wave myocardial infarction and major
      vascular and bleeding complications. At six-month follow-up, the mortality rate
      was higher in patients with CRF, 7.6% compared with 1.9% in non-CRF patients (p =
      0.003). Restenosis, target lesion revascularization (TLR) and target vessel
      revascularization (TVR) rates were similar in the two groups. In patients with
      CRF, radiation therapy compared to placebo reduced restenosis (53.8% vs. 22.6%, p
      = 0.04), TLR (71.4% vs. 15.3%, p < 0.0001) and TVR (78.6% vs. 23.7%, p = 0.0002).
      CONCLUSIONS: Intracoronary radiation for the prevention of recurrence of in-stent
      restenosis achieved similar rates of restenosis and revascularization procedures
      in patients with and without CRF. Despite this benefit, patients with renal
      dysfunction continued to have significantly higher in-hospital and six-month
      adverse outcomes.

PMID- 11583882
TI  - Elective stenting of unprotected left main coronary artery stenosis: effect of
      debulking before stenting and intravascular ultrasound guidance.
AB  - OBJECTIVES: We sought to evaluate: 1) the long-term outcomes of 127 selected
      patients receiving unprotected left main coronary artery (LMCA) stenting; and 2)
      the impact of the debulking procedure before stenting and intravascular
      ultrasound (IVUS) guidance on their clinical outcomes. BACKGROUND: The long-term
      safety of stenting of unprotected LMCA stenoses has not been established yet.
      METHODS: A total of 127 consecutive patients with unprotected LMCA stenosis and
      normal left ventricular function were treated by elective stenting. The long-term
      outcomes were evaluated between two groups: IVUS guidance (n = 77) vs.
      angiographic guidance (n = 50); and debulking plus stenting (debulking/stenting;
      n = 40) vs. stenting only (n = 87). RESULTS: Angiographic restenosis was
      documented in 19 (19%) of 100 patients. The lumen diameter after stenting was
      significantly larger in IVUS-guided group (p = 0.003). The angiographic
      restenosis rate was significantly lower in the debulking/stenting group (8.3% vs.
      25%, p = 0.034). The reference artery size was the only independent predictor of
      angiographic restenosis. During follow-up (25.5 +/- 16.7 months), there were four
      deaths, but no nonfatal myocardial infarctions occurred. The survival rate was
      97.0 +/- 1.7% at two years. CONCLUSIONS: These data suggest that stenting of
      unprotected LMCA stenosis might be associated with a favorable long-term outcome
      in selected patients. Guidance with IVUS may optimize the immediate results, and
      debulking before stenting seems to be effective in reducing the restenosis rate.
      However, we need a large-scale, randomized study.

PMID- 11583883
TI  - Influence of planned six-month follow-up angiography on late outcome after
      percutaneous coronary intervention: a randomized study.
AB  - OBJECTIVES: The goal of this research was to study the effect of planned
      angiography on late clinical outcome after percutaneous coronary intervention.
      BACKGROUND: It is still largely unknown whether planned follow-up angiography
      after coronary angioplasty influences late outcome. METHODS: Randomization
      assigned 527 patients to clinical follow-up alone and 531 to clinical and six
      month angiographic follow-up. The effect of planned angiography on clinical
      outcome at one and three years after coronary angioplasty was studied. RESULTS:
      The two groups were well matched. At one year, more events occurred in the
      angiographic group than in the clinical group: 122 (23.2%) versus 88 (16.7%) (p =
      0.01). While the incidence of death or myocardial infarction (MI) was similar at
      one year, the revascularization rate was higher in the angiographic group: 113
      (21.3%) versus 67 (12.7%) (relative risk = 1.7, 95% confidence interval: 1.3 to
      2.3, p = 0.0003). At three years, still more events had occurred in the
      angiographic group (146 [34.5%] vs. 114 [26.3%], p = 0.03). More reinterventions
      did not improve late survival. However, there was a nonsignificant reduction in
      MI (7 [1.3%] vs. 13 [2.5%], p = NS) and a significant improvement in functional
      class at the end of follow-up (freedom from angina 81% vs. 74%, p = 0.03). The
      effect of follow-up angiography on the reintervention rate was similar for
      stented and nonstented patients. CONCLUSIONS: Planned follow-up angiography to
      evaluate the late results of coronary intervention led to a 1.7 times higher
      reintervention rate. This effect was similar for stented and nonstented patients.
      More reinterventions did not improve survival but tended to reduce the incidence
      of MI and led to a significantly better functional class at follow-up.

PMID- 11583884
TI  - Increased mortality after coronary artery bypass graft surgery is associated with
      increased levels of postoperative creatine kinase-myocardial band isoenzyme
      release: results from the GUARDIAN trial.
AB  - OBJECTIVES: We sought to determine if elevated cardiac serum biomarkers after
      coronary artery bypass graft surgery (CABG) are associated with increased medium
      term mortality and to identify patients that may benefit from better
      postoperative myocardial protection. BACKGROUND: The relationship between the
      magnitude of cardiac serum protein elevation and subsequent mortality after CABG
      is not well defined, partly because of the lack of large, prospectively studied
      patient cohorts in whom postoperative elevations of cardiac serum markers have
      been correlated to medium- and long-term mortality. METHODS: The GUARD during
      Ischemia Against Necrosis (GUARDIAN) study enrolled 2,918 patients assigned to
      the entry category of CABG and considered as high risk for myocardial necrosis.
      Creatine kinase-myocardial band (CK-MB) isoenzyme measurements were obtained at
      baseline and at 8, 12, 16 and 24 h after CABG. RESULTS: The unadjusted six-month
      mortality rates were 3.4%, 5.8%, 7.8% and 20.2% for patients with a postoperative
      peak CK-MB ratio (peak CK-MB value/upper limits of normal [ULN] for laboratory
      test) of < 5, > or = 5 to <10, > or =10 to < 20 and > or =20 ULN, respectively (p
      < 0.0001). The relationship remained statistically significant after adjustment
      for ejection fraction, congestive heart failure, cerebrovascular disease,
      peripheral vascular disease, cardiac arrhythmias and the method of cardioplegia
      delivery. Receiver operating characteristic curve analysis revealed an area under
      the curve of 0.648 (p < 0.001); the optimal cut-point to predict six-month
      mortality ranged from 5 to 10 ULN. CONCLUSIONS: Progressive elevation of the CK
      MB ratio in clinically high-risk patients is associated with significant
      elevations of medium-term mortality after CABG. Strategies to afford myocardial
      protection both during CABG and in the postoperative phase may serve to improve
      the clinical outcome.

PMID- 11583885
TI  - C-reactive protein is increased in patients with degenerative aortic valvular
      stenosis.
AB  - OBJECTIVES: The goal of this study was to assess the presence of systemic
      inflammation in degenerative aortic valvular stenosis. BACKGROUND: Local
      inflammatory changes, resembling those observed in atherosclerosis, have been
      recently reported in degenerative aortic valvular stenosis. It is presently
      unknown whether systemic signs of inflammation, similar to those observed in
      atherosclerosis, may be present in this disorder. METHODS: C-reactive protein
      (CRP) was measured by enzyme immunoassay in 141 subjects: 62 with trileaflet
      degenerative valvular aortic stenosis and 79 volunteers with similar demographic
      and clinical characteristics. IgG antibodies against Helicobacter pylori (enzyme
      linked immunosorbant assay) and Chlamydia pneumoniae (microimmunofluorescence
      assay) were also measured. RESULTS: C-reactive protein levels (mg/dl, mean +/-
      SD) were 0.848 +/- 1.42 in patients and 0.394 +/- 0.50 in controls (p = 0.0001,
      Mann-Whitney U test). Seroprevalence of H. pylori was 68.7% in patients and 79.7%
      in controls (p = NS), whereas seroprevalence of C. pneumoniae infection was
      higher in patients than it was in controls (59.7% vs. 33%, p = 0.003; chi-square
      test). After adjustment for various covariates in multiple logistic regression,
      the odds ratio for degenerative aortic stenosis was 3.41 for C. pneumoniae
      infection (95% confidence intervals [CI]: 1.60 to 7.30) and 2.76 for CRP (95% CI:
      1.08 to 7.05). There was no significant difference in patients or controls in CRP
      levels according to the serostatus for C. pneumoniae. CONCLUSIONS: Systemic signs
      of inflammation, similar to those found in atherosclerosis, are present in
      patients with degenerative aortic valve stenosis. They do not seem to be linked
      to C. pneumoniae or H. pylori infection.

PMID- 11583886
TI  - Repeated thermal therapy improves impaired vascular endothelial function in
      patients with coronary risk factors.
AB  - OBJECTIVES: We sought to determine whether sauna therapy, a thermal vasodilation
      therapy, improves endothelial function in patients with coronary risk factors
      such as hypercholesterolemia, hypertension, diabetes mellitus and smoking.
      BACKGROUND: Exposure to heat is widely used as a traditional therapy in many
      different cultures. We have recently found that repeated sauna therapy improves
      endothelial and cardiac function in patients with chronic heart failure. METHODS:
      Twenty-five men with at least one coronary risk factor (risk group: 38 +/- 7
      years) and 10 healthy men without coronary risk factors (control group: 35 +/- 8
      years) were enrolled. Patients in the risk group were treated with a 60 degrees C
      far infrared-ray dry sauna bath for 15 min and then kept in a bed covered with
      blankets for 30 min once a day for two weeks. To assess endothelial function,
      brachial artery diameter was measured at rest, during reactive hyperemia (flow
      mediated endothelium-dependent dilation [%FMD]), again at rest and after
      sublingual nitroglycerin administration (endothelium-independent vasodilation
      [%NTG]) using high-resolution ultrasound. RESULTS: The %FMD was significantly
      impaired in the risk group compared with the control group (4.0 +/- 1.7% vs. 8.2
      +/- 2.7%, p < 0.0001), while %NTG was similar (18.7 +/- 4.2% vs. 20.4 +/- 5.1%).
      Two weeks of sauna therapy significantly improved %FMD in the risk group (4.0 +/-
      1.7% to 5.8 +/- 1.3%, p < 0.001). In contrast, %NTG did not change after two
      weeks of sauna therapy (18.7 +/- 4.2% to 18.1 +/- 4.1%). CONCLUSIONS: Repeated
      sauna treatment improves impaired vascular endothelial function in the setting of
      coronary risk factors, suggesting a therapeutic role for sauna treatment in
      patients with risk factors for atherosclerosis.

PMID- 11583887
TI  - Angiotensin type 1 receptor antagonism reverses abnormal coronary vasomotion in
      atherosclerosis.
AB  - OBJECTIVES: This study was performed to determine whether angiotensin type 1
      (AT1) receptor inhibition improves abnormal coronary vasomotion and endothelial
      dysfunction in patients with atherosclerosis or its risk factors. BACKGROUND:
      Endothelial dysfunction, an early feature of atherosclerosis, contributes to
      abnormal vasomotion during stress. Angiotensin II may contribute to endothelial
      dysfunction in atherosclerosis. METHODS: In 25 patients, mean age 59 +/- 2 years,
      with atherosclerosis or its risk factors, we measured coronary vasomotion during
      flow-mediated dilation (FMD) in response to adenosine, cold pressor test (CPT)
      and exercise before and after AT1 receptor blockade with intracoronary losartan
      (5 mg). RESULTS: Losartan did not alter resting coronary vascular tone, but
      epicardial FMD improved from 5.6 +/- 1.5% to 8.9 +/- 1.8% (p = 0.02). Abnormal
      epicardial vasomotion during CPT and exercise also improved with losartan from 
      1.7 +/- 0.8% to 1.5 +/- 0.1% (p = 0.02) and -0.6 +/- 0.9% to 3.4 +/- 1.2% (p =
      0.009), respectively. Improvement in epicardial vasomotion was most prominent in
      segments with baseline endothelial dysfunction evidenced as constriction during
      stress. Microvascular dilation during adenosine, an endothelium-independent
      response, was unchanged with losartan. CONCLUSIONS: Inhibition of the coronary
      vascular AT1 receptors in patients with atherosclerosis improves epicardial
      vasomotion during stress, probably by improving endothelial dysfunction. Whether
      AT1 receptor blockade will provide long-term therapeutic benefits in
      atherosclerosis needs further investigation.

PMID- 11583888
TI  - Evidence supporting abnormalities in nitric oxide synthase function induced by
      nitroglycerin in humans.
AB  - OBJECTIVES: We studied the effects of nitroglycerin (GTN) therapy on the response
      to endothelium-dependent and independent vasoactive agents in the forearm
      circulation of healthy subjects. BACKGROUND: Recent evidence suggests that
      therapy with GTN may induce specific changes in endothelial cell function,
      including increased superoxide anion production and sensitivity to
      vasoconstrictors. Additionally, continuous GTN therapy worsens endothelial
      function in the coronary circulation of patients with ischemic heart disease.
      METHODS: Forearm blood flow was measured with venous occlusion, mercury-in
      silastic strain gauge plethysmography. RESULTS: Sixteen male volunteers (26 +/- 6
      years) were randomized to no therapy (control) or GTN, 0.6 mg/h/24 h, for six
      days in an investigator-blind, parallel-design study. The flow responses to
      brachial artery infusions of acetylcholine ([Ach] 7.5, 15.0, 30.0 microg/min), N
      monomethyl-L-arginine (L-NMMA) (1, 2, 4 micromol/min) and sodium nitroprusside
      (SNP) (0.8, 1.6, 3.2 microg/min) were recorded. The vasodilator responses to Ach
      were blunted in the GTN group as compared with the control group (p < 0.05). The
      vasoconstrictor responses to L-NMMA were also blunted in the GTN group (p <
      0.001). In the GTN group, paradoxical vasodilation was observed in response to
      the lowest infused concentration of L-NMMA. The vasodilator responses to SNP did
      not differ between groups. CONCLUSIONS: The response to Ach confirms the
      hypothesis that continuous GTN causes endothelial dysfunction. The responses to L
      NMMA suggest that GTN therapy causes abnormalities in nitric oxide synthase (NOS)
      function; the vasodilation observed at the lowest infused concentration of L-NMMA
      in the GTN group also suggests that continuous GTN therapy is associated with a
      NOS-mediated production of a vasoconstrictor.

PMID- 11583889
TI  - Does nitroglycerin therapy hit the endothelium?

PMID- 11583890
TI  - Mechanisms responsible for endothelial dysfunction induced by fasting
      hyperhomocystinemia in normotensive subjects and patients with essential
      hypertension.
AB  - OBJECTIVES: We sought to evaluate whether fasting hyperhomocystinemia reduces
      endothelial function by oxidative stress in normotensive subjects and
      hypertensive patients. BACKGROUND: Subjects with hyperhomocystinemia have
      endothelial dysfunction. METHODS: In 23 normotensive subjects and 28 hypertensive
      patients, classified into normohomocystinemic and hyperhomocystinemic groups
      according to homocysteine plasma levels (< 8.7 and >14.6 micromol/l,
      respectively), we studied forearm blood flow changes (strain-gauge
      plethysmography) induced by intrabrachial administration of acetylcholine (0.15
      to 15 microg/100 ml tissue per min) or sodium nitroprusside (1 to 4 microg/100 ml
      per min), an endothelium-dependent and -independent vasodilator, respectively.
      Acetylcholine was repeated with N(G)-monomethyl-L-arginine (L-NMMA; 100
      microg/100 ml per min), vitamin C (8 mg/100 ml per min) and L-NMMA plus vitamin
      C. RESULTS: Normotensive hyperhomocystinemic patients showed a blunted response
      to acetylcholine and a lower inhibiting effect of L-NMMA on acetylcholine, as
      compared with normohomocystinemic patients. Although vitamin C was ineffective in
      normohomocystinemic subjects, it increased the response to acetylcholine and
      restored the inhibiting effect of L-NMMA on acetylcholine in hyperhomocystinemic
      patients. Hypertensive hyperhomocystinemic patients showed a reduced response to
      acetylcholine, as compared with normohomocystinemic subjects. In both subgroups,
      L-NMMA failed to blunt the response to acetylcholine. The potentiating effect of
      vitamin C on acetylcholine was greater in hyperhomocystinemic patients than in
      normohomocystinemic subjects, although it restored the inhibitory effect of L
      NMMA on acetylcholine-induced vasodilation to the same extent in both groups.
      Hyperhomocystinemia did not change the response to sodium nitroprusside.
      CONCLUSIONS: In normotensive subjects and hypertensive patients,
      hyperhomocystinemia impairs endothelium-dependent vasodilation. It could be
      related to oxidant activity.

PMID- 11583891
TI  - Anti-ischemic effects of angiotensin- converting enzyme inhibition in
      hypertension.
AB  - OBJECTIVES: We investigated whether augmentation of bradykinin (BK)
      bioavailability with angiotensin-converting enzyme (ACE) inhibition is associated
      with reduced exercise-induced myocardial ischemia in hypertension. BACKGROUND:
      Bradykinin responses are depressed in hypertension, and endothelial dysfunction
      contributes to myocardial ischemia by promoting abnormal coronary vasomotion
      during stress. METHODS: Fourteen hypertensive (HT) and 17 normotensive (NT),
      mildly symptomatic patients with coronary artery disease (CAD) and ST-segment
      depression during exercise were studied before and after seven days of oral
      enalapril (EN), which was titrated from 2.5 to 20 mg daily. Patients underwent
      two treadmill exercise tests and determination of forearm vasodilator response to
      BK. RESULTS: Despite receiving a lower dose of EN (7.8 vs. 14.8 mg, p < 0.001),
      NT patients had a significant reduction in blood pressure compared to HT
      patients. Compared to pre-EN, the ischemic threshold, defined as the rate
      pressure product at the onset of 1-mm ST depression (p = 0.045), the duration of
      exercise to 1-mm ST depression (180 +/- 54 s, p = 0.007) and the maximum exercise
      duration (94 +/- 18 s, p < 0.001) were greater after EN in HT patients, but not
      in NT subjects (all p > or = 0.3). Patients with a greater drop in blood pressure
      experienced no improvement in exercise-induced ischemia. Forearm blood flow
      responses to BK were improved with EN in all patients to a similar extent.
      Moreover, no correlation was observed between the basal response to BK or the
      magnitude of its improvement with EN and with either the dose of EN or the
      improvement in exercise ischemic threshold. CONCLUSIONS: Exercise-induced
      myocardial ischemia is ameliorated in HT patients with CAD by ACE inhibition.

PMID- 11583892
TI  - Age-associated changes in regional aortic pulse wave velocity.
AB  - OBJECTIVES: This study was designed to determine noninvasively the age-associated
      changes in regional mechanical properties in normals using phase-contrast
      magnetic resonance imaging (PCMRI). BACKGROUND: It has been well documented that
      there is a progressive increase in aortic pulse wave velocity (PWV) with age.
      Previously, PWV has been measured at a single aortic location, or has compared
      arterial waves between carotid and femoral points to determine PWV. METHODS:
      Applanation tonometry (TONO) and in-plane PCMR was performed in 24 volunteers (12
      men) ranging in age from 21 to 72 years old. The PCMRI PWV was measured in three
      aortic segments. As validation, TONO was performed to determine PWV between the
      carotid and femoral artery. RESULTS: When PCMRI PWV was averaged over the three
      locations, it was not different from TONO (7.9 +/- 2.3 vs. 7.6 +/- 2.4 m/s,
      respectively). When the volunteers were divided into groups of < 55 and > or =55
      years old, the younger group showed similar PWV at each aortic location. However,
      the older group displayed significantly increased PWV in the region spanning the
      ascending and proximal descending aorta compared with the mid-thoracic or
      abdominal segments (10.6 +/- 2.5 m/s, 9.2 +/- 2.8 m/s, and 7.1 +/- 1.7 m/s,
      respectively, p < 0.001, analysis of variance). CONCLUSIONS: In-plane PCMRI
      permits determination of PWV in multiple aortic locations in a single
      acquisition. Progressive fragmentation of elastic fibers and alterations in the
      regulation of vascular tone may result in an age-related, regional increase in
      PWV primarily affecting the proximal aorta.

PMID- 11583893
TI  - Atrial natriuretic peptide in severe primary and nonprimary pulmonary
      hypertension: response to iloprost inhalation.
AB  - OBJECTIVES: The goal of this study was to assess atrial natriuretic peptide (ANP)
      levels during inhalation of iloprost in severe primary (PPH) and nonprimary
      pulmonary hypertension (NPPH). BACKGROUND: The ANP system is activated in
      pulmonary hypertension and may help protect from right ventricular (RV)
      decompensation. It is unknown if ANP regulation is the same in severe PPH and
      NPPH and if the dynamic regulation is intact in a highly activated ANP system.
      METHODS: In 11 patients with PPH and seven patients with NPPH, right heart
      catheter investigations were performed. Pulmonary and systemic artery ANP and
      cyclic guanosine monophosphate (cGMP) levels as well as hemodynamics were
      measured before and after iloprost inhalation. RESULTS: The baseline hemodynamics
      of patients with PPH and patients with NPPH were comparable (mean pulmonary
      artery pressure [mPAP]: 61 +/- 5 mm Hg vs. 52 +/- 5 mm Hg, pulmonary vascular
      resistance [PVR]: 1,504 +/- 153 dyne.s.cm(-5) vs. 1,219 +/- 270 dyne.s.cm(-5).
      Atrial natriuretic peptide and cGMP levels were increased about tenfold and
      fivefold compared with controls in both PPH and NPPH. Iloprost inhalation
      significantly decreased mPAP (-9.1 +/- 2.5 mm Hg vs. -7.9 +/- 1.5 mm Hg), PVR (
      453 +/- 103 dyne.s.cm(-5) vs. -381 +/- 114 dyne.s.cm(-5)), ANP (-99 +/- 63 pg/ml
      vs. -108 +/- 47 pg/ml) and cGMP (-4.6 +/- 0.9 nM vs. -4.2 +/- 1.6 nM). Baseline
      ANP including all patients significantly correlated with PVR, right atrial
      pressure, cardiac index, RV ejection fraction, mixed venous oxygen saturation and
      cGMP. CONCLUSIONS: The ANP system is highly activated in patients with severe PPH
      and NPPH. Atrial natriuretic peptide levels are significantly correlated with
      parameters of RV function and pre- and afterload. Iloprost inhalation causes a
      rapid decrease in ANP and cGMP in parallel with pulmonary vasodilation and
      hemodynamic improvement.

PMID- 11583894
TI  - Right ventricular ischemia in patients with primary pulmonary hypertension.
AB  - OBJECTIVES: The goal of this study was to determine whether right ventricular
      (RV) ischemia is a contributory factor in the development of RV dysfunction in
      patients with primary pulmonary hypertension (PPH). BACKGROUND: Patients with
      advanced PPH develop RV dysfunction, characterized by a decreased cardiac output,
      increased right atrial pressure (RAP) and/or elevated RV end-diastolic pressure,
      which progresses to heart failure and death. The cause of this dysfunction is
      unknown. Right ventricular ischemia may play a role in its development. METHODS:
      From 1992 to 1999, a prospective study involving 23 patients with PPH at the
      Instituto Nacional de Cardiologia "Ignacio Chavez" (Mexico City, Mexico) was
      undertaken. These patients were evaluated clinically and further studied by
      echocardiography, right heart catheterization and stress myocardial scintigraphy
      using technetium 99m sestamibi. RESULTS: Nine patients of 23 were found to have
      scintigraphic images consistent with RV ischemia. Significant correlation was
      found between RV ischemia obtained through myocardial perfusion scintigraphy and
      elevation of RV end-diastolic pressure (p < 0.001), elevation of RAP (p < 0.037)
      and a decrease in mixed venous oxygen saturation (p < 0.0001). No other clinical
      or hemodynamic variables showed a significant correlation with RV ischemia.
      CONCLUSIONS: A direct correlation exists between RV ischemia, as determined by
      myocardial scintigraphy, and hemodynamic alterations suggestive of RV dysfunction
      in patients with PPH.

PMID- 11583895
TI  - Electrophysiologic characteristics of paroxysmal and chronic atrial fibrillation
      in human right atrium.
AB  - OBJECTIVES: The aim of the study was to analyze the electrophysiologic
      characteristics of paroxysmal (PAF) and chronic (CAF) atrial fibrillation (AF) in
      the human right atrium (RA). BACKGROUND: Differences that exist between PAF and
      CAF and the mechanisms of self-sustenance of these arrhythmias are incompletely
      understood. METHODS: A total of 53 patients with PAF (25 patients, mean age 59 +/
      6.1 years, 3 women) and CAF (28 patients, mean age 59 +/- 13 years, 7 women)
      underwent multisite mapping of the RA during ongoing AF using a 64-electrode
      basket catheter. Quantitative evaluation and three-dimensional activation
      patterns were performed using a computerized system. RESULTS: Patients with PAF,
      as compared with patients with CAF, had significantly longer AF cycle length,
      shorter time intervals with type III AF throughout the RA and a smaller number of
      endocardial breakthroughs (mean 51 +/- 19 vs. 104 +/- 40, p < 0.001). The
      majority of endocardial breakthrough points (88% in PAF patients and 98% in CAF
      patients) were located in the septal region and coincided anatomically with major
      interatrial connection routes. Coexistence of re-entrant and apparently focal
      activation determined maintenance of AF in the RA in PAF, whereas random re-entry
      was documented more frequently in patients with CAF. In patients with CAF, the
      duration of arrhythmia (in years) correlated strongly with the percentage of time
      during which type III AF was observed in the lateral wall of the RA (r = 0.71).
      CONCLUSIONS: Clinical PAF and CAF, as recorded in the RA, have, at least
      quantitatively, distinct electrophysiologic features and different mechanisms of
      maintenance.

PMID- 11583896
TI  - Temporal decline in defibrillation thresholds with an active pectoral lead
      system.
AB  - OBJECTIVES: The objective of this study was to characterize temporal changes in
      defibrillation thresholds (DFTs) after implantation with an active pectoral, dual
      coil transvenous lead system. BACKGROUND: Ventricular DFTs rise over time when
      monophasic waveforms are used with non-thoracotomy lead systems. This effect is
      attenuated when biphasic waveforms are used with transvenous lead systems;
      however, significant increases in DFT still occur in a minority of patients. The
      long-term stability of DFTs with contemporary active pectoral lead systems is
      unknown. METHODS: This study was a prospective assessment of temporal changes in
      DFT using a uniform testing algorithm, shock polarity and dual-coil active
      pectoral lead system. Thresholds were measured at implantation, before discharge
      and at long-term follow-up (70 +/- 40 weeks) in 50 patients. RESULTS: The DFTs
      were 9.2 +/- 5.4 J at implantation, 8.3 +/- 5.8 J before discharge and 6.9 +/-
      3.6 J at long-term follow-up (p < 0.01 by analysis of variance; p < 0.05 for long
      term follow-up vs. at implantation or before discharge). The effect was most
      marked in a prespecified subgroup with high implant DFTs (> or =15 J). No patient
      developed an inadequate safety margin (< 9 J) during follow-up. CONCLUSIONS: The
      DFTs declined significantly after implantation with an active pectoral, dual-coil
      transvenous lead system, and no clinically significant increases in DFT were
      observed. Therefore, routine defibrillation testing may not be required during
      the first two years after implantation with this lead system, in the absence of a
      change in the cardiac substrate or treatment with antiarrhythmic drugs.

PMID- 11583897
TI  - Differences in inducibility and prognosis of in-hospital versus out-of-hospital
      identified nonsustained ventricular tachycardia in patients with coronary artery
      disease: clinical and trial design implications.
AB  - OBJECTIVES: The goal of this study was to describe the influence of the clinical
      setting (in-hospital vs. out-of-hospital) in which nonsustained ventricular
      tachycardia (NSVT) is discovered on the rate of inducibility of sustained
      ventricular tachycardia (VT), arrhythmic events and survival in patients with
      coronary artery disease (CAD) and left ventricular (LV) dysfunction. BACKGROUND:
      In-hospital presentation of sustained VT is independently associated with lower
      long-term overall survival. The impact of the clinical setting in which NSVT is
      documented is unknown. METHODS: In the Multicenter Unsustained Tachycardia Trial
      (MUSTT), designed to assess the benefit of randomized antiarrhythmic therapy
      guided by electrophysiologic testing in patients with asymptomatic NSVT, CAD and
      LV dysfunction, eligible patients were enrolled irrespective of the setting in
      which the index arrhythmia was discovered. In this retrospective analysis, we
      compared the rate of VT inducibility and outcome of MUSTT-enrolled patients with
      in-hospital versus out-of-hospital presentation of NSVT. RESULTS: Monomorphic
      sustained VT was induced in 35% and 28% of the patients whose index NSVT occurred
      in-hospital and out-of-hospital, respectively (adjusted p = 0.006). Cardiac
      arrest or death due to arrhythmia at two- and five-year follow-ups were 14% and
      28% for untreated patients with in-hospital-identified NSVT and 11% and 21% for
      the out-of-hospital group (adjusted p = 0.10). Overall mortality rates at two-
      and five-year follow-ups were 24% and 48% for inpatients and 18% and 38% for
      outpatients (adjusted p = 0.018). In patients randomized to antiarrhythmic
      therapy, there was no significant interaction between patient status (in-hospital
      vs. out-of-hospital) and treatment impact on the rates of total mortality (p =
      0.98) and arrhythmic events (p = 0.08). CONCLUSIONS: In patients with CAD and
      impaired LV function, asymptomatic NSVT identified in-hospital, compared with
      that identified out-of-hospital, is associated with a higher rate of induction of
      sustained VT and overall mortality. Therefore, in similar patients, the clinical
      setting in which NSVT is discovered should be taken into account when formulating
      patient risk, treatment and clinical trial design.

PMID- 11583898
TI  - Differentiation of atypical atrioventricular node re-entrant tachycardia from
      orthodromic reciprocating tachycardia using a septal accessory pathway by the
      response to ventricular pacing.
AB  - OBJECTIVES: The purpose of this study was to determine whether the response to
      ventricular pacing during tachycardia is useful for differentiating atypical
      atrioventricular node re-entrant tachycardia (AVNRT) from orthodromic
      reciprocating tachycardia (ORT) using a septal accessory pathway. BACKGROUND:
      Although it is usually possible to differentiate atypical AVNRT from ORT using a
      septal accessory pathway, a definitive diagnosis is occasionally elusive.
      METHODS: In 30 patients with atypical AVNRT and 44 patients with ORT using a
      septal accessory pathway, the right ventricle was paced at a cycle length 10 to
      40 ms shorter than the tachycardia cycle length (TCL). The ventriculo-atrial (VA)
      interval and TCL were measured just before pacing. The interval between the last
      pacing stimulus and the last entrained atrial depolarization (stimulus-atrial [S
      A] interval) and the post-pacing interval (PPI) at the right ventricular apex
      were measured on cessation of ventricular pacing. RESULTS: All 30 patients with
      atypical AVNRT and none of the 44 patients with ORT using a septal accessory
      pathway had an S-A-VA interval >85 ms and PPI-TCL >115 ms. CONCLUSIONS: The S-A
      VA interval and PPI-TCL are useful in distinguishing atypical AVNRT from ORT
      using a septal accessory pathway.

PMID- 11583899
TI  - Pause-dependent torsade de pointes following acute myocardial infarction: a
      variant of the acquired long QT syndrome.
AB  - OBJECTIVES: We report on a previously unrecognized form of the long QT syndrome
      (QT interval prolongation and pause-dependent polymorphic ventricular tachycardia
      [VT]) entirely related to myocardial infarction (MI). BACKGROUND: Polymorphic VT
      in the setting of acute MI generally occurs during the hyperacute phase, is
      related to ischemia, and is not associated with QT prolongation. Although QT
      prolongation after MI is well described, typical pause-dependent polymorphic VT
      (torsade de pointes) secondary to uncomplicated MI was previously unknown.
      METHODS: Of 434 consecutive admissions for acute MI, 8 patients had progressive
      QT prolongation that led to typical torsade de pointes. None of these patients
      had active ischemia or other known causes of QT prolongation. These patients were
      compared with 100 consecutive patients with uncomplicated MI who served as
      controls. RESULTS: The incidence of torsade de pointes following MI was 1.8% (95%
      confidence interval 0.8% to 3.6%). The QTc intervals of patients and controls
      were similar on admission. The QTc lengthened by day 2 in both groups, but more
      so in patients with torsade de pointes (from 470 +/- 46 to 492 +/- 57 ms [p <
      0.05] and from 445 +/- 58 to 558 +/- 84 ms, respectively [p < 0.01]). Maximal QT
      prolongation and torsade de pointes occurred 3 to 11 days after infarction.
      Therapy included defibrillation, magnesium, lidocaine and beta-blockers. Three
      patients required rapid cardiac pacing. The long-term course was uneventful.
      CONCLUSIONS: Infarct-related torsade de pointes is uncommon but potentially
      lethal. An acquired long QT syndrome should be considered in patients recovering
      from MI who experience polymorphic VT as specific therapeutic measures are
      mandatory.

PMID- 11583900
TI  - Expression profiling of cardiac genes in human hypertrophic cardiomyopathy:
      insight into the pathogenesis of phenotypes.
AB  - OBJECTIVES: The goal of this study was to identify genes upregulated in the heart
      in human patients with hypertrophic cardiomyopathy (HCM). BACKGROUND:
      Hypertrophic cardiomyopathy is a genetic disease caused by mutations in
      contractile sarcomeric proteins. The molecular basis of diverse clinical and
      pathologic phenotypes in HCM remains unknown. METHODS: We performed polymerase
      chain reaction-select complementary DNA subtraction between normal hearts and
      hearts with HCM and screened subtracted libraries by Southern blotting. We
      sequenced the differentially expressed clones and performed Northern blotting to
      detect increased expression levels. RESULTS: We screened 288 independent clones,
      and 76 clones had less than twofold increase in the signal intensity and were
      considered upregulated. Sequence analysis identified 36 genes including those
      encoding the markers of pressure overload-induced ("secondary") cardiac
      hypertrophy, cytoskeletal proteins, protein synthesis, redox system, ion channels
      and those with unknown function. Northern blotting confirmed increased expression
      of skeletal muscle alpha-actin (ACTA1), myosin light chain 2a (MLC2a), GTP
      binding protein Gs-alpha subunit (GNAS1), NADH ubiquinone oxidoreductase
      (NDUFB10), voltage-dependent anion channel 1 (VDAC1), four-and-a-half LIM domain
      protein 1 (FHL1) (also known as SLIM1), sarcosin (SARCOSIN) and heat shock 70kD
      protein 8 (HSPA8) by less than twofold. Expression levels of ACTA1, MLC2a and
      GNAS1 were increased in six additional and FHL1 in four additional hearts with
      HCM. CONCLUSIONS: A diverse array of genes is upregulated in the heart in human
      patients with HCM, which could account for the diversity of clinical and
      pathologic phenotypes. Markers of secondary hypertrophy are also upregulated,
      suggesting commonality of pathways involved in HCM and the acquired forms of
      cardiac hypertrophy. Elucidation of the role of differentially expressed genes in
      HCM could provide for new therapeutic targets.

PMID- 11583901
TI  - A comparison of treatment strategies for hypoplastic left heart syndrome using
      decision analysis.
AB  - OBJECTIVES: We sought to identify the optimal treatment strategy for hypoplastic
      left heart syndrome (HLHS). BACKGROUND: Surgical treatment of HLHS involves
      either transplantation (Tx) or staged palliation of the native heart. Identifying
      the best treatment for HLHS requires integrating individual patient risk factors
      and center-specific data. METHODS: Decision analysis is a modeling technique used
      to compare six strategies: staged surgery; Tx; stage 1 surgery as an interim to
      Tx; and listing for transplant for one, two, or three months before performing
      staged surgery if a donor is unavailable. Probabilities were derived from current
      literature and a dataset of 231 patients with HLHS born between 1989 and 1994.
      The goal was to maximize first-year survival. RESULTS: If a donor is available
      within one month, Tx is the optimal choice, given baseline probabilities; if no
      donor is found by the end of one month, stage 1 surgery should be performed. When
      survival and organ donation probabilities were varied, staged surgery was the
      optimal choice for centers with organ donation rates < 10% in three months and
      with stage 1 mortality <20%. Waiting one month on the transplant list optimized
      survival when the three-month organ donation rate was > or =30%. Performing stage
      1 surgery before listing, or performing stage 1 surgery after an unsuccessful two
      or three-month wait for transplant, were almost never optimal choices.
      CONCLUSIONS: The best strategy for centers that treat patients with HLHS should
      be guided by local organ availability, stage 1 surgical mortality and patient
      risk factors.

PMID- 11583902
TI  - Attenuation of angiotensin II-mediated coronary vasoconstriction and vasodilatory
      action of angiotensin-converting enzyme inhibitor in pacing-induced heart failure
      in dogs.
AB  - OBJECTIVES: We investigated the changes in coronary vascular resistance caused by
      angiotensin II, angiotensin-converting enzyme (ACE) inhibition and angiotensin II
      type 1 or 2 receptor (AT(1)R and AT(2)R, respectively) antagonists in chronic
      heart failure (CHF). BACKGROUND: Angiotensin II is an intense vasoconstrictor,
      and increased angiotensin II in CHF might exert significant vasoconstriction.
      METHODS: Eleven dogs were studied. Before and after three and five weeks of rapid
      pacing, coronary flow dynamics were evaluated by the coronary pressure-flow
      relationship (PFR) in long diastole, before and after intracoronary injection of
      angiotensin II, the ACE inhibitor enalaprilat, the AT(1)R antagonist L158,809 or
      the AT(2)R antagonist PD123319. RESULTS: Before rapid pacing, angiotensin II
      reduced the slope of PFR (1.16 +/- 0.08 to 0.81 +/- 0.07 ml/min/100 g left
      ventricular mass per mm Hg; p < 0.01) and increased the perfusion pressure at
      which coronary flow ceased (zero-flow pressure [P(f) = 0]), whereas enalaprilat
      did not change either of them. After rapid pacing, angiotensin II did not change
      the slope or P(f) = 0. In contrast, enalaprilat increased the slope (three weeks:
      1.20 +/- 0.05 to 1.50 +/- 0.03; five weeks: 1.25 +/- 0.19 to 1.37 +/- 0.08; both
      p < 0.05) and decreased P(f) = 0 after three weeks of pacing, but not after five
      weeks. Pretreatment with the bradykinin antagonist HOE-140 attenuated the
      enalaprilat-induced increase in coronary blood flow. L158,809 and PD123319 had no
      effect both before and after rapid pacing. CONCLUSIONS: This suggests that the
      coronary vasoconstrictive effect of angiotensin II would disappear and the
      vasodilatory effect of the ACE inhibitor, partly through bradykinin, would be
      enhanced in the early stage of CHF.

PMID- 11583903
TI  - Interaliasing distance of the flow convergence surface for determining mitral
      regurgitant volume: a validation study in a chronic animal model.
AB  - OBJECTIVES: We aimed to validate a new flow convergence (FC) method that
      eliminated the need to locate the regurgitant orifice and that could be performed
      semiautomatedly. BACKGROUND: Complex and time-consuming features of previously
      validated color Doppler methods for determining mitral regurgitant volume (MRV)
      have prevented their widespread clinical use. METHODS: Thirty-nine different
      hemodynamic conditions in 12 sheep with surgically created flail leaflets
      inducing chronic mitral regurgitation were studied with two-dimensional (2D)
      echocardiography. Color Doppler M-mode images along the centerline of the
      accelerating flow towards the mitral regurgitation orifice were obtained. The
      distance between the two first aliasing boundaries (interaliasing distance [IAD])
      was measured and the FC radius was mathematically derived according to the
      continuity equation (R(calc) = IAD/(1 - radicalv(1)/v(2)), v(1) and v(2) being
      the aliasing velocities). The conventional 2D FC radius was also measured
      (R(meas)). Mitral regurgitant volume was then calculated according to the FC
      method using both R(calc) and R(meas). Aortic and mitral electromagnetic (EM)
      flow probes and meters were balanced against each other to determine the
      reference standard MRV. RESULTS: Mitral regurgitant volume calculated from
      R(calc) and R(meas) correlated well with EM-MRV (y = 0.83x + 5.17, r = 0.90 and y
      = 1.04x + 0.91, r = 0.91, respectively, p < 0.001 for both). However, both
      methods resulted in slight overestimation of EM-MRV (Delta was 3.3 +/- 2.1 ml for
      R(calc) and 1.3 +/- 2.3 ml for R(meas)). CONCLUSIONS: Good correlation was
      observed between MRV derived from R(calc) (IAD method) and EM-MRV, similar to
      that observed with R(meas) (conventional FC method) and EM-MRV. The R(calc) using
      the IAD method has an advantage over conventional R(meas) in that it does not
      require spatial localization of the regurgitant orifice and can be performed
      semiautomatedly.

PMID- 11583904
TI  - Interaliasing distances to assess mitral regurgitation: dividing the rainbow of
      flow convergence.

PMID- 11583905
TI  - Effects of combination of angiotensin-converting enzyme inhibitor and angiotensin
      receptor antagonist on inflammatory cellular infiltration and myocardial
      interstitial fibrosis after acute myocardial infarction.
AB  - OBJECTIVES: The goal of this study was to compare the relative efficacy of an
      angiotensin-converting enzyme (ACE) inhibitor and an angiotensin receptor blocker
      (ARB) in suppressing the histopathologic changes that lead to ventricular
      remodeling after an acute myocardial infarction (AMI). BACKGROUND: Myocardial
      interstitial fibrosis in the noninfarcted region is a major histologic landmark
      resulting in cardiac dysfunction after AMI. However, the relative potency of an
      ACE inhibitor and ARB on suppressing the histopathologic changes was unclear.
      METHODS: Rats with AMI were randomized to fosinopril, valsartan or a combination
      of the two drugs for two or four weeks. The total, type I and type III collagen
      and activated fibroblasts and macrophages were quantified by histomorphometry.
      The expression of transforming growth factor-beta 1 (TGF-beta 1) messenger
      ribonucleic acid (mRNA) was determined by reverse transcription polymerase chain
      reaction. RESULTS: Acute myocardial infarction resulted in significant elevation
      of total (p < 0.001) and type I (p < 0.001) collagen and a twofold increase in
      TGF-beta 1 mRNA expression (p < 0.001) in the septum at two and four weeks.
      Macrophages and activated myofibroblasts infiltrated extensively in the infarct
      zone. Treatment with valsartan or combination therapy normalized the total and
      type I collagen (p < 0.001) as well as TGF-beta 1 mRNA level (p < 0.01) in the
      septum and was associated with the suppression of macrophages and myofibroblasts
      in the infarct zone (p < 0.01). Fosinopril was less effective than valsartan or
      combination therapy. CONCLUSIONS: The use of valsartan, especially combined with
      fosinopril, was more effective than fosinopril in the suppression of
      histopathologic changes resulting in cardiac remodeling after AMI. This study has
      important therapeutic implications in pharmacotherapy of clinical practice.

PMID- 11583906
TI  - Moderate hypothermia during cardiopulmonary bypass reduces myocardial cell damage
      and myocardial cell death related to cardiac surgery.
AB  - OBJECTIVES: The goal of this study was to test the hypothesis that moderate
      hypothermia during cardiopulmonary bypass (CPB) provides myocardial protection by
      enhancing intra-myocardial anti-inflammatory cytokine balance. BACKGROUND:
      Moderate hypothermia during experimental CPB stimulates production of interleukin
      10 (IL10) and blunts release of tumor necrosis factor-alpha (TNFalpha). METHODS:
      Twelve young pigs were assigned to a temperature (T degrees ) regimen during CPB:
      moderate hypothermia (T degrees : 28 degrees C; n = 6) and normothermia (T
      degrees : 37 degrees C; n = 6). Intra-myocardial TNFalpha- and IL10-messenger RNA
      were detected by competitive reverse transcriptase polymerase chain reaction and
      quantification of cytokine synthesis by Western blot. Levels of cardiac troponin
      I (cTnI) in cardiac lymph and in arterial and coronary venous blood were examined
      during and after CPB. Myocardial cell damage was assessed by histologic and
      ultrastructural anomalies of tissue probes taken 6 h after CPB. RESULTS:
      Synthesis of IL10 was significantly higher, while that of TNFalpha was
      significantly lower, in pigs that were in moderate hypothermia during surgery
      than in the others. In contrast with normothermia, moderate hypothermia was also
      associated with significantly lower cumulative cardiac lymphatic flow during and
      after CPB, significantly lower lymphatic cTnI concentrations after CPB,
      significantly lower percentages of myocardial cell necrosis and a significantly
      lower score of ultrastructural anomalies of myocardial cells. While the
      percentage of apoptotic cells was not different between groups, the
      apoptosis/necrosis ratio tended to be higher in animals that were in moderate
      hypothermia during surgery. In all animals, TNFalpha synthesis correlated
      positively while IL10 production correlated negatively with necrosis and total
      cell death, respectively. CONCLUSIONS: Our results suggest that moderate
      hypothermia during CPB provides myocardial protection by enhancing intra
      myocardial anti-inflammatory cytokine balance.

PMID- 11583907
TI  - Should an abnormal serum potassium concentration be considered a correctable
      cause of cardiac arrest?
AB  - According to American Heart Association/American College of Cardiology Practice
      Guidelines, electrolyte abnormalities, including abnormal serum potassium
      concentrations, are considered a correctable cause of a life-threatening
      ventricular arrhythmia. Ventricular defibrillator therapy in this situation is a
      class III indication, and thought to be ineffective and perhaps harmful, although
      there are minimal data to support this recommendation. The steady-state serum
      potassium concentration frequently changes during a cardiac arrest. Additionally,
      the vast majority of cardiac arrest patients have structural heart disease and
      are commonly treated with a variety of medications that can alter the serum
      potassium concentration. In the Antiarrhythmics Versus Implantable Defibrillators
      (AVID) trial, patients with a correctable cause of an electrolyte imbalance were
      excluded from study participation but were followed in the AVID registry. Similar
      outcomes were observed among patients in the AVID registry and the main trial.
      Spironolactone therapy in patients with congestive heart failure decreases all
      cause mortality and sudden and nonsudden cardiac death. In a preliminary study of
      169 patients with an episode of a sustained ventricular arrhythmia treated with
      an implantable defibrillator, freedom from appropriate defibrillator therapy was
      18% after five years. The probability of appropriate defibrillator therapy was
      independent of the initial serum potassium concentration. For these reasons, our
      current clinical practice is to use an implantable defibrillator to treat an
      initial episode of sustained ventricular tachycardia or ventricular fibrillation
      that occurs in a patient with structural heart disease and an abnormal serum
      potassium concentration.

PMID- 11583908
TI  - What is our contract with society?

PMID- 11583909
TI  - President's page: the future of print.

PMID- 11583910
TI  - ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation:
      executive summary. A Report of the American College of Cardiology/ American Heart
      Association Task Force on Practice Guidelines and the European Society of
      Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to
      Develop Guidelines for the Management of Patients With Atrial Fibrillation):
      developed in Collaboration With the North American Society of Pacing and
      Electrophysiology.

PMID- 11583913
TI  - Regulation of MAP kinase activity by peptide receptor signalling pathway:
      paradigms of multiplicity.
AB  - G protein-coupled receptors (GPCRs) can stimulate the mitogen-activated protein
      kinase (MAPK) cascade and thereby induce cellular proliferation like receptor
      tyrosine kinases (RTKs). Work over the past 5 years has established several
      models which reduce the links of G(i)-, G(q)-, and G(s)-coupled receptors to MAPK
      on few principle pathways. They include (i) Ras-dependent activation of MAPK via
      transactivation of RTKs such as the epidermal growth factor receptor (EGFR), (ii)
      Ras-independent MAPK activation via protein kinase C (PKC) that converges with
      the RTK signalling at the level of Raf, and (iii) activation as well as
      inactivation of MAPK via the cAMP/protein kinase A (PKA) pathway in dependency on
      the type of Raf. Most of these generalizing hypotheses are founded on
      experimental data obtained from expression studies and using a limited set of
      individual receptors. This review will compare these models with pathways to MAPK
      found for a great variety of peptide hormone and neuropeptide receptor subtypes
      in various cells. It becomes evident that under endogenous conditions, the
      transactivation pathway is less dominant as postulated, whereas pathways
      involving isoforms of PKC and, especially, phosphoinositide 3-kinase (PI-3K)
      appear to play a more important role as assumed so far. Highly cell-specific and
      unusual connections of signalling proteins towards MAPK, in particular tumour
      cells, might provide points of attacks for new therapeutic concepts.

PMID- 11583914
TI  - Regulation of Gadd45a mRNA expression in vascular smooth muscle under growth and
      stress conditions.
AB  - In order to identify differentially expressed genes under growth conditions,
      quiescent vascular smooth muscle cells (VSMCs) were stimulated with foetal calf
      serum (FCS) or platelet-derived growth factor-BB (PDGF-BB) for different time
      periods. Analysing the gene expression by the differential display (DD) method,
      we identified the cDNA of the growth arrest and DNA damage inducible gene 45a
      (Gadd45a, also known as gadd45 and gadd45a). Treatment with FCS or PDGF-BB led to
      a transient down-regulating of Gadd45a expression during the G0/G1 phase and
      maximal expression when cells had completed division. We found that expression of
      p53 and BRCA1 mRNA precedes Gadd45a mRNA expression with a maximal induction in
      the S phase. As in smooth muscle cells, a similar pattern of the Gadd45a mRNA
      expression was observed in knockout Gadd45a(-/-) cultured mouse embryonic
      fibroblasts (MEFs). However, no differences between Gadd45a(+/+) and Gadd45a(-/-)
      cell lines were observed regarding their kinetics of cell division. These
      experiments suggest a function of Gadd45a when cells exit the cell cycle rather
      than when regulating the entry into the S phase.

PMID- 11583915
TI  - Induction of cyclooxygenase-2 synthesis by ligation of the macrophage alpha(2)
      macroglobulin signalling receptor.
AB  - We have studied the induction of cyclooxygenase-2 (COX-2) in macrophages
      consequent to ligating the alpha(2)-macroglobulin (alpha(2)M) signalling receptor
      (alpha(2)MSR) with receptor-recognized forms of alpha(2)M (alpha(2)M*).
      Macrophage stimulation with alpha(2)M* increased total cellular and nuclear COX-2
      two- to threefold. The maximal increase in COX-2 occurred at a ligand
      concentration of 50-100 pM and after 2 h. Modulation of intracellular Ca(2+)
      levels or incubation of [35S] methionine-labelled macrophages with actinomycin D,
      prior to treatment with alpha(2)M*, markedly reduced the induction of total
      cellular and nuclear COX-2. Protein kinase C (PKC) or phospholipase A(2) (PLA(2))
      inhibition in alpha(2)M*-stimulated macrophages or inhibition of the p21(ras)
      dependent mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase
      (PI 3-kinase) signalling pathways also significantly reduced alpha(2)M*-induced
      total cellular and nuclear COX-2 expression. Thus, COX-2 induction is dependent
      on cPLA(2) activity, Ca(2+) mobilization, and PKC activity and requires
      participation of both the p21(ras)-dependent MAPK and PI 3-kinase signalling
      pathways. COX-2 activation may mediate alpha(2)M*-induced mitogenesis, which we
      have previously observed in this and other cell types.

PMID- 11583916
TI  - Evidence for involvement of c-Src in the anti-apoptotic action of nitric oxide in
      serum-deprived RINm5F cells.
AB  - The mechanism by which nitric oxide (NO) protects from apoptosis is a matter of
      debate. We have shown previously that phosphorylation of tyrosine residues
      participates in the protection from apoptosis in insulin-producing RINm5F cells
      (Inorg. Chem. Commun. 3 (2000) 32). Since NO has been reported to activate the
      tyrosine kinase c-Src and this kinase is involved in the activation of protein
      kinase G (PKG) in some cell systems, we aimed at studying the contribution of c
      Src and PKG systems in anti-apoptotic actions of NO in serum-deprived RINm5F
      cells. Here we report that exposure of serum-deprived cells to 10 microM DETA/NO
      results in protection from degradation of the anti-apoptotic protein Bcl-2,
      together with a reduction of cytochrome c release from mitochondria and caspase-3
      inhibition. Studies with the inhibitors ODQ and KT-5823 revealed that these
      actions are dependent on both activation of guanylate cyclase and PKG. DETA/NO
      was also able to induce autophosphorylation and activation c-Src protein both in
      vivo and in vitro and active c-Src was able to induce tyrosine phosphorylation of
      Bcl-2 in vitro. The c-Src kinase inhibitor PP1 abrogated the actions of DETA/NO
      on cGMP formation, PKG activation, caspase activation, cytochrome c release from
      mitochondria, and Bcl-2 phosphorylation and degradation in serum-deprived cells.
      We thus propose that activation of c-Src is an early step in the chain of events
      that signal cGMP-dependent anti-apoptotic actions of NO in mitocohondria.

PMID- 11583917
TI  - Prolactin induces calcium influx and release from intracellular pools in human T
      lymphocytes by activation of tyrosine kinases.
AB  - The early events related to intracellular signals after prolactin (PRL)
      activation in T lymphocytes are not clearly established. The aim of this work was
      to study the effect of PRL in cytosolic calcium levels in human T lymphocytes. By
      using the dye FURA-2 AM, the variations in cytosolic Ca(2+) were studied in
      peripheral human T lymphocytes isolated from extracted blood from healthy donors.
      Fifty nanograms per milliliter PRL induces a small increase in cytosolic calcium.
      When the cells are preincubated overnight (16-20 h) in the presence of PRL, the
      increase in calcium is higher. This high increase is due to the release from
      intracellular pools and to the influx from the extracellular media. That is,
      after overnight incubation with PRL, calcium influx in T cells follows the
      capacitative model. Since PRL receptor (PRL-R) activation involves the tyrosine
      kinase pathway, we check calcium effect in the presence of genistein, a known
      inhibitor of tyrosine kinases. When cells are preincubated in the presence of 10
      microM genistein, and PRL is immediately added, no increase in cytosolic calcium
      is observed. The presence of genistein also completely blocks the increase in
      cytosolic calcium stimulated by PRL after overnight incubation with PRL. In the
      presence of PRL and N,N-dimethyl-D-erythro-sphingosine (DMS), a stimulus that
      increases cytosolic calcium in T cells by tyrosine kinase stimulation, a high,
      even insignificant, calcium influx is induced. However, when the cells are
      incubated overnight in the presence of PRL, and then DMS is added, a significant
      increase in cytosolic calcium levels takes place. This increase is associated
      with an increase in calcium release from intracellular pools and an increase in
      calcium uptake. Genistein reduces the influx of external calcium induced by DMS
      after short incubation with PRL and significantly inhibits both, calcium pools
      empty, and calcium influx is induced by DMS after overnight incubation with PRL.
      In summary, PRL induces calcium influx in normal T lymphocytes. The influx is
      magnified after long PRL exposures, intracellular Ca(2+) pool-dependent, and
      activated through tyrosine kinases.

PMID- 11583918
TI  - Modulation of the leptin-induced white adipose tissue lipolysis by nitric oxide.
AB  - The present study tested the hypothesis that nitric oxide (NO) is involved in the
      leptin-induced stimulation of lipolysis. The effect of intravenous (iv)
      administration of leptin (10, 100 and 1000 microg/kg body weight) or vehicle on
      serum NO concentrations and glycerol release from white adipocytes of Wistar rats
      was examined. One hour after injection, the three leptin doses tested increased
      serum NO concentrations 15.1%, 23.4% and 60.0%, respectively (P<.001 vs.
      baseline). The effect of leptin on NO concentrations was significantly dose
      dependent on linear trend testing (P=.0001). Simple linear regression analysis
      showed that the lipolytic rate measured was significantly correlated with serum
      NO concentrations (P=.0025; r=.52). In order to gain further insight into the
      potential underlying mechanisms, the effect of leptin on lipolysis was studied in
      the setting of nitric oxide synthase (NOS) inhibition or acute ganglionic
      blockade. The stimulatory effect of leptin on lipolysis was significantly
      decreased (P<.05) under NOS inhibition. On the contrary, the leptin-induced
      lipolysis was unaltered in pharmacologically induced ganglionic blockade. The
      lack of effect on isoproterenol-, forskolin- and dibutyryl-cyclic AMP-stimulated
      lipolysis suggests that leptin does not interfere with the signal transduction
      pathway at the beta-adrenergic receptor, the adenylate cyclase and the protein
      kinase A levels. These findings suggest that NO is a potential regulator of
      leptin-induced lipolysis.

PMID- 11583919
TI  - MafG-2 is a novel Maf protein that is expressed by stimulation of extracellular
      H(+).
AB  - We cloned MafG-2, a novel splice variant of MafG, from rat brain by RT-PCR
      method. MafG-2 differs from the previously published MafG by an insertion of 27
      amino acids. Sequence analysis of the cDNA-encoded MafG-2 showed that MafG-2
      contains basic domain and basic leucine zipper (bZip) motif. Transient
      transfection studies with GFP-MafG-2 chimera protein indicate that MafG-2 is
      localized in the nuclei of transfected COS-7 cells. To determine whether gene
      expression of mafG-2 mRNA is induced by an increase in extracellular protons, we
      analyzed expression of the mRNA in PC12 cells after an increase in extracellular
      proton concentration. We found that the mafG-2 mRNA expression increased when
      extracellular pH was decreased gradually from 7.40 to 7.20 and that there was a
      significant correlation between extracellular pH value and the expression of mafG
      2 mRNA. These results suggest that an increase in extracellular proton may induce
      the expression of mafG-2 mRNA and MafG-2 may be involved in signal transduction
      of extracellular of H(+).

PMID- 11583920
TI  - Factors affecting prostacyclin receptor agonist efficacy in different cell types.
AB  - Octimibate and related nonprostanoid prostacyclin mimetics are partial agonists
      displaying highly tissue-specific responses. Octimibate demonstrated considerably
      greater efficacy for stimulation of adenylyl cyclase activity in Chinese hamster
      ovary cells transiently expressing mouse prostacyclin receptors (mIP-CHO cells)
      when compared to human SK-N-SH neuroblastoma cells, which endogenously express
      prostacyclin (IP) receptors. Pretreatment of both cell types with pertussis toxin
      (PTx) failed to influence IP agonist efficacy or potency, indicating a lack of
      involvement of an agonist-stimulated inhibitory G(i)-coupled pathway. Although
      stimulation of mIP-CHO cells with the full agonist cicaprost increased both
      [3H]cyclic AMP and [3H]inositol phosphate ([3H]IP) accumulation (pEC(50) values
      of 8.35 and 6.82, respectively), IP receptor signalling through G(q) in SK-N-SH
      cells was absent. Inhibition of protein kinase C (PKC) in mIP-CHO cells increased
      [3H]IP accumulation but had no effect on [3H]cyclic AMP accumulation. Therefore,
      the poor coupling of the IP receptor in SK-N-SH cells to G(q) is unlikely to
      explain the relatively low efficacy of octimibate for stimulating adenylyl
      cyclase in these cells. Furthermore, protein kinase A (PKA) inhibition appears to
      enhance IP receptor signalling through both G(s) and G(q) in mIP-CHO cells.

PMID- 11583921
TI  - Signal transduction by VEGF receptor-1 wild type and mutant proteins.
AB  - The role of the vascular endothelial growth factor receptor-1 (VEGFR-1) in
      endothelial cell function is unclear. We have previously identified four tyrosine
      phosphorylation sites in the C-terminal tail of this receptor. We now show that
      the wild type VEGFR-1 expressed in porcine aortic endothelial (PAE/VEGFR-1) cells
      was able to transduce signals for increased DNA synthesis and proliferation.
      Tyrosine phosphorylation of phospholipase Cgamma (PLCgamma), tyrosine phosphatase
      SHP-2, Crk, and extracellular regulated kinases 1 and 2 (Erk1/2) was registered
      in response to VEGF-A treatment of the PAE/VEGFR-1 cells. VEGFR-1 mutated at
      Y1213, Y1242, and Y1333 were constructed and expressed in PAE cells, to the same
      level as that of PAE/VEGFR-1 cells. The affinities of the wild type and mutated
      receptors for VEGF-A(165) binding were similar. The mutated VEGFR-1 Y1213F
      expressed in PAE cells was kinase inactive. PAE cells expressing the mutated
      VEGFR-1 Y1242F and Y1333F receptors mediated increased tyrosine phosphorylation
      of PLCgamma in response to VEGF-A stimulation. However, these two mutant VEGFR-1
      failed to mediate increased mitogenesis and were unable to stimulate increased
      tyrosine phosphorylation of SHP-2, Crk, and Erk1/2, indicating that the mutations
      lead to a perturbation in VEGF-A-induced signal transduction.

PMID- 11583922
TI  - Managing uncertainty in diagnosis of acute coronaric ischemia.
AB  - The paper presents the reasoning mechanism of COR, a knowledge-based system (KBS)
      able to provide support for the diagnosis of coronaric ischemia by integrating
      the interpretation of chest pain, 12-lead ECG, and bio-marker concentrations.
      Chest pain features are collected interactively through a questionnaire. The ECG
      signal is acquired in SCP format. Any set of bio-markers can be considered. Data
      input is incremental and possibly incomplete. Reasoning is based on revised
      uncertainty calculus, which allows a formal treatment of verbally expressed
      uncertainty concerning both input data and diagnostic rules. Each diagnosis is
      supplemented by a linguistic label, expressing the plausibility of the disease
      identified, given the symptoms observed.

PMID- 11583923
TI  - Knowledge discovery approach to automated cardiac SPECT diagnosis.
AB  - The paper describes a computerized process of myocardial perfusion diagnosis from
      cardiac single proton emission computed tomography (SPECT) images using data
      mining and knowledge discovery approach. We use a six-step knowledge discovery
      process. A database consisting of 267 cleaned patient SPECT images (about 3000 2D
      images), accompanied by clinical information and physician interpretation was
      created first. Then, a new user-friendly algorithm for computerizing the
      diagnostic process was designed and implemented. SPECT images were processed to
      extract a set of features, and then explicit rules were generated, using
      inductive machine learning and heuristic approaches to mimic cardiologist's
      diagnosis. The system is able to provide a set of computer diagnoses for cardiac
      SPECT studies, and can be used as a diagnostic tool by a cardiologist. The
      achieved results are encouraging because of the high correctness of diagnoses.

PMID- 11583924
TI  - Case-based reasoning for antibiotics therapy advice: an investigation of
      retrieval algorithms and prototypes.
AB  - We have developed an antibiotics therapy advice system called ICONS for patients
      in an intensive care unit (ICU) who have caught an infection as additional
      complication. Since advice for such critically ill patients is needed very
      quickly and as the actual pathogen still has to be identified by the laboratory,
      we use an expected pathogen spectrum based on medical background knowledge and
      known resistances. The expected pathogen spectra and the resistance information
      are periodically updated from laboratory results. To speed up the process of
      finding suitable therapy recommendations, we have applied case-based reasoning
      (CBR) techniques. As all required information should always be up to date in
      medical expert systems, new cases should be incrementally incorporated into the
      case base and outdated ones should be updated or erased. For reasons of space
      limitations and of retrieval time an indefinite growth of the case base should be
      avoided. To fulfill these requirements we propose that specific single cases
      should be generalised to more general prototypical ones and that subsequent
      redundant cases should be erased. In this paper, we present evaluation results of
      different generation strategies for generalised cases (prototypes). Additionally,
      we compare measured retrieval times for two indexing retrieval algorithms: simple
      indexing, which is appropriate for small and medium case bases, and tree-hash
      retrieval, which is advantageous for large case bases.

PMID- 11583925
TI  - Feature subset selection by genetic algorithms and estimation of distribution
      algorithms. A case study in the survival of cirrhotic patients treated with TIPS.
AB  - The transjugular intrahepatic portosystemic shunt (TIPS) is an interventional
      treatment for cirrhotic patients with portal hypertension. In the light of our
      medical staff's experience, the consequences of TIPS are not homogeneous for all
      the patients and a subgroup dies in the first 6 months after TIPS placement.
      Actually, there is no risk indicator to identify this subgroup of patients before
      treatment. An investigation for predicting the survival of cirrhotic patients
      treated with TIPS is carried out using a clinical database with 107 cases and 77
      attributes. Four supervised machine learning classifiers are applied to
      discriminate between both subgroups of patients. The application of several
      feature subset selection (FSS) techniques has significantly improved the
      predictive accuracy of these classifiers and considerably reduced the amount of
      attributes in the classification models. Among FSS techniques, FSS-TREE, a new
      randomized algorithm inspired on the new EDA (estimation of distribution
      algorithm) paradigm has obtained the best average accuracy results for each
      classifier.

PMID- 11583926
TI  - Efficient transformation of the yellow fever mosquito Aedes aegypti using the
      piggyBac transposable element vector pBac[3xP3-EGFP afm].
AB  - We report efficient germ-line transformation in the yellow fever mosquito Aedes
      aegypti accomplished using the piggyBac transposable element vector pBac[3xP3
      EGFP afm]. Two transgenic lines were established and characterized; each
      contained the Vg-Defensin A transgene with strong eye-specific expression of the
      enhanced green fluorescent protein (EGFP) marker gene regulated by the artificial
      3xP3 promoter. Southern blot hybridization and inverse PCR analyses of genomic
      DNA demonstrated a precise piggyBac-mediated, single copy insertion of the
      pBac[3xP3-EGFP afm,Vg-DefA] transposon in each transgenic line. For each line,
      genetic analysis confirmed stability and integrity of the entire transposon
      construct in the mosquito genome through the G2-G6 generations. Successful
      establishment of homozygous transgenic lines indicated that in both cases a non
      lethal integration of the transposon into the mosquito genome had occurred. The
      3xP3-EGFP marker was tested in mosquitoes with different genetic backgrounds. In
      white-eyed transgenic mosquitoes, the strong eye-specific expression of GFP was
      observed throughout all stages of development, starting from newly hatched first
      instar larvae to adults. A similar level and pattern of fluorescence was observed
      in red-eyed mosquitoes that were generated by crossing the 3xP3-EGFP
      transformants with the kh(w) white-eye mosquitoes transformed with the Drosophila
      cinnabar gene. Importantly, the utility of the 3xP3-EGFP, as marker gene for
      transformation of wild type mosquitoes, was demonstrated by strong eye-specific
      GFP expression in larval and pupal stages of black-eyed hybrids of the 3xP3-EGFP
      white-eye transformants and the wild type Rockefeller/UGAL strain. Finally,
      analysis of the Vg-DefA transgene expression in transformants from two
      established lines demonstrated strong blood-meal activation and fat-body-specific
      expression regulated by the Vg 1.8-kb 5' upstream region.

PMID- 11583927
TI  - Identification and cloning of a key insecticide-metabolizing glutathione S
      transferase (MdGST-6A) from a hyper insecticide-resistant strain of the housefly
      Musca domestica.
AB  - Strains of the housefly, Musca domestica, highly resistant to organophosphate
      (OP) and other insecticides are known because they overproduce glutathione S
      transferases (GSTs). Previous work has shown that overproduction in these strains
      involved numerous isozymes with glutathione conjugating activities (Pesticide
      Biochem. Physiol., 25 (1986) 169; Mol. General Genetics, 227 (1991) 355; J. Biol.
      Chem., 267 (1992) 1840; Mol. General Genetics, 245 (1994) 236; J. Mol. Evol., 43
      (1996) 236). The current work describes the purification and identification of a
      M. domestica GST isozyme (pI 7.1) broadly specific for substrates from a housefly
      strain, Cornell-HR, that is highly resistant against OP-insecticides, and the
      isolation of two new MdGST genes using the antibody made against it. This
      isozyme, which was identified from amongst more than 20 isoelectric forms of GSTs
      of the same subunit size, was highly active for conjugating GSH to the model
      substrate 3,4-dichloronitrobenzne (DCNB). When expressed in Escherichia coli, one
      of the cloned GSTs, MdGST-6A, produces an enzyme that conjugates glutathione to
      the insecticides methyl parathion and lindane. On indication that it was the most
      active isozyme toward several xenobiotics among several MdGSTs tested, we advance
      the notion that MdGST-6A probably plays an important role in M. domestica Cornell
      HR's resistance towards OP-insecticides. MdGST-6A and a second closely related
      one found in this work, MdGST-6B, are members of the traditional insect class I
      family (theta-class) and share the greatest homologies with a cluster of
      Drosophila GSTs on locus 55. In addition to having the unusually broad substrate
      specificity, the sequence of the new group of enzymes reveals that it has a
      highly diverged hydrophobic motif in its active site as compared to other class I
      GSTs from insects.

PMID- 11583928
TI  - Processing of Cry1Ab delta-endotoxin from Bacillus thuringiensis by Manduca sexta
      and Spodoptera frugiperda midgut proteases: role in protoxin activation and toxin
      inactivation.
AB  - Activation of Cry protoxins is carried out by midgut proteases. This process is
      important for toxicity and in some cases for specificity. Commercial proteases
      have been used for in vitro protoxin activation. In the case of Cry1A protoxins,
      trypsin digestion generates a toxic fragment of 60-65 kDa. Here, we have analyzed
      the in vitro and in vivo activation of Cry1Ab. We found differences in the
      processing of Cry1Ab protoxin by Manduca sexta and Spodoptera frugiperda midgut
      proteases as compared to trypsin. Midgut juice proteases produced two additional
      nicks at the N-terminal end removing helices alpha1 and alpha2a to produce a 58
      kDa protein. A further cleavage within domain II splits the toxin into two
      fragments of 30 kDa. The resulting fragments were not separated, but instead
      coeluted with the 58 kDa monomer, in size-exclusion chromatography. To examine if
      this processing was involved in the activation or degradation of Cry1Ab toxin,
      binding, pore formation, and toxicity assays were performed. Pore formation
      assays showed that midgut juice treatment produced a more active toxin than
      trypsin treatment. In addition, it was determined that the alpha1 helix is
      dispensable for Cry1Ab activity. In contrast, the appearance of the 30 kDa
      fragments correlates with a decrease in pore formation and insecticidal
      activities. Our results suggest that the cleavage in domain II may be involved in
      toxin inactivation, and that the 30 kDa fragments are stable intermediates in the
      degradation pathway.

PMID- 11583929
TI  - Cloning of two hexokinase isoenzyme sequences from Drosophila melanogaster.
AB  - Hexokinase coding DM1 and DM2 sequences were obtained from genomic DNA of a
      Drosophila melanogaster cell line by PCR amplification strategy. Both the
      sequences were found to encode an enzyme with a molecular weight of 50,000 Da.
      Amino acid sequence alignment of DM1 and DM2 shows approximately 45% homology
      with yeast and human hexokinases. The sequences also indicated the presence of
      conserved amino acid residues and motifs that are present in mammalian
      hexokinases and are involved in the binding of different substrates. Southern
      blot analysis suggests that the D. melanogaster genome contain a single copy of
      DM1 and DM2 sequences. Northern analysis indicates DM1 is expressed as more than
      one transcript in adult as well as in the D.Mel2 cell line. DM2 is expressed as a
      single transcript in adult flies. Expression levels for DM1 and DM2 encoded
      message were found to be similar in different stages of development as seen by RT
      PCR. The biotechnological significance of these sequences in metabolic
      engineering of cells is discussed.

PMID- 11583930
TI  - Identity and expression pattern of chemosensory proteins in Heliothis virescens
      (Lepidoptera, Noctuidae).
AB  - Analyzing the chemosensory organs of the moth Heliothis virescens, three proteins
      belonging to the family of insect chemosensory proteins (CSPs) have been cloned;
      they are called HvirCSP1, HvirCSP2 and HvirCSP3. The HvirCSPs show about 50%
      identity between each other and 30-76% identity to CSPs from other species.
      Overall, they are rather hydrophilic proteins but include a conserved hydrophobic
      motif. Tissue distribution and temporal expression pattern during the last pupal
      stages were assessed by Northern blots. HvirCSP mRNAs were detected in various
      parts of the adult body with a particular high expression level in legs. The
      expression of HvirCSP1 in legs started early during adult development, in
      parallel with the appearance of the cuticle. HvirCSP1 mRNA was detectable five
      days before eclosion (day E-5), increased dramatically on day E-3 and remained at
      high level into adult life. The tissue distribution and the time course of
      appearance of HvirCSPs are in agreement with a possible role in contact
      chemosensation.

PMID- 11583931
TI  - Purification and sequence determination of a yellow protein from sexually mature
      males of the desert locust, Schistocerca gregaria.
AB  - A yellow protein from abdominal cuticle of the desert locust, Schistocerca
      gregaria, has been purified and its amino acid sequence determined. The yellow
      color comes from bound carotene, the protein is only deposited in the epidermis
      and cuticle of male locusts during their sexual maturation, and the deposition is
      dependent upon a sufficiently high titer of juvenile hormone. The sequence of the
      protein is atypical for a cuticular protein, but it has some similarity to a
      putative juvenile hormone binding protein from Manduca sexta. It is suggested
      that the protein is involved in the transport of carotenes from internal tissues
      to epidermis and cuticle of the locust.

PMID- 11583932
TI  - Esterase isozyme polymorphism, specific and nonspecific esterase, syngenic lines
      development and natural occurrence of a thermostable esterase in the tropical
      silkworm Bombyx mori L.
AB  - Esterase isozyme polymorphism was documented for digestive juice and haemolymph
      of the tropical multivoltine silkworm, Bombyx mori L., breed CB5 (GP) and its
      syngenic lines (CB5Lm(e)-1, CB5Lm-2 and CB5Lm-5) using alpha- and beta
      naphthylacetate separately as nonspecific substrates (Ogita, Z., Kasai, T., 1965.
      Genetico-biochemical analysis of specific esterases in Musca domestica. Jpn. J.
      Genet. 40, 173-184). Polymorphism existed in the isozyme pattern of alpha
      esterase with two or three bands in digestive juice and three to five bands in
      haemolymph. No polymorphism was observed in beta-esterase isozyme pattern having
      four bands in digestive juice and two bands in haemolymph. During the course of
      esterase isozyme studies, the presence of some specific alpha-esterase bands (Est
      1, 4 and 5) in haemolymph and beta-esterase bands (Est-1, 2 and 3) in digestive
      juice were observed. But both alpha- and beta-esterase bands Est-3 and 4 in
      digestive juice and Est-2 and 3 in haemolymph were found to be nonspecific.
      Nonspecific beta-esterase band (Est-3) in haemolymph of CB5 (GP) and its syngenic
      lines withstood a temperature up to 80+/-1 degrees C for 10 min. No thermostable
      band was observed in the isozyme zymogram of alpha-esterase in digestive juice
      and haemolymph or beta-esterase in digestive juice. Overall, this study discusses
      the presence of esterase heterogeneity in the CB5 (GP) genepool, syngenic lines
      development, occurrence of specific alpha- and beta-esterase bands in digestive
      juice and haemolymph and thermostable beta-esterase band Est-3 in haemolymph in
      tropical silkworm Bombyx mori L.

PMID- 11583933
TI  - The mechanism of sex-specific splicing at the doublesex gene is different between
      Drosophila melanogaster and Bombyx mori.
AB  - We have previously reported that Bmdsx, a homologue of the sex-determining gene,
      doublesex (dsx), was found to be sex-specifically expressed in various tissues at
      larval, pupal, and adult stages in the silkworm, Bombyx mori, and was
      alternatively spliced to yield male- and female-specific mRNAs. To reveal sex
      specific differences in splicing patterns of Bmdsx pre-mRNA, the genomic sequence
      was determined and compared with male- and female-specific Bmdsx cDNA sequences.
      The open reading frame (ORF) consisted of five exons. Exons 3 and 4 were
      specifically incorporated into the female type of Bmdsx mRNA. On the other hand,
      exon 2 was spliced to exon 5 to produce the male type mRNA of Bmdsx. As in the
      case of Drosophila dsx, the OD2 domain was separated by a female-specific intron
      into sex-independent and sex-dependent regions. Sex-specific splicing occurred in
      equivalent positions in the Drosophila dsx gene. However, unlike Drosophila dsx,
      the female-specific introns showed no weak 3' splice sites, and the TRA/TRA-2
      binding site related sequences were not found in the female-specific exon, nor
      even in any other regions of the Bmdsx gene. Moreover, an in vitro splicing
      reaction consisting of HeLa cell nuclear extracts showed that the female-type of
      Bmdsx mRNA represented the default splicing. These findings suggest that the
      structural features of the sex-specific splicing patterns of Bmdsx pre-mRNA are
      similar to those of Drosophila dsx but the regulation of sex-specific alternative
      splicing of Bmdsx pre-mRNA is different.

PMID- 11583934
TI  - Isolation and expression of an ecdysteroid-inducible neutral endopeptidase 24.11
      like gene in wing discs of Bombyx mori.
AB  - In the process of comparison of two cDNA libraries (W0, W2), we isolated a clone
      from the wing discs of Bombyx mori encoding a putative neutral endopeptidase
      24.11-like gene. The predicted open reading frame encoded 772 amino acid
      residues, having about 53% identity with Drosophila GH07643, 36% with rat NEP,
      and 34% with rat ECE. This is the first NEP gene isolated in invertebrate. A 3.6
      kb transcript was found to accumulate in the wing disc according to the increase
      of ecdysteroid titer during metamorphosis. Accumulation of the transcript was
      induced in wing discs with 20-hydroxyecdysone about 20h after incubation, which
      was inhibited by cycloheximide. This gene is ecdysone-inducible, appears to
      encode a functional protein, and may function during wing metamorphosis.

PMID- 11583935
TI  - Properties of Manduca sexta chitinase and its C-terminal deletions.
AB  - Manduca sexta (tobacco hornworm) chitinase is a molting enzyme that contains
      several domains including a catalytic domain, a serine/threonine-rich region, and
      a C-terminal cysteine-rich domain. Previously we showed that this chitinase acts
      as a biopesticide in transgenic plants where it disrupts gut physiology. To
      delineate the role of these domains further and to identify and characterize some
      of the multiple forms produced in molting fluid and in transgenic plants, three
      different forms with variable lengths of C-terminal deletions were generated.
      Appropriately truncated forms of the M. sexta chitinase cDNA were generated,
      introduced into a baculovirus vector, and expressed in insect cells. Two of the
      truncated chitinases (Chi 1-407 and Chi 1-477) were secreted into the medium,
      whereas the one with the longest deletion (Chi 1-376) was retained inside the
      insect cells. The two larger truncated chitinases and the full-length enzyme (Chi
      1-535) were purified and their properties were compared. Differences in
      carbohydrate compositions, pH-activity profiles, and kinetic constants were
      observed among the different forms of chitinases. All three of these chitinases
      had some affinity for chitin, and they also exhibited differences in their
      ability to hydrolyze colloidal chitin. The results support the hypothesis that
      multiple forms of this enzyme occur in vivo due to proteolytic processing at the
      C-terminal end and differential glycosylation.

PMID- 11583936
TI  - Selective binding of Drosophila BR-C isoforms to a distal regulatory element in
      the hsp23 promoter.
AB  - The Broad-Complex (BR-C) gene plays a key role in the ecdysone regulatory
      hierarchy. Together with other early ecdysone-inducible genes BR-C transmits the
      hormonal signal to a set of secondary response genes in a tissue-specific manner.
      Among its targets is the hsp23 gene. Previously we showed that expression of the
      hsp23 gene in late third instar is BR-C-dependent, and accompanied by the
      appearance of a BR-C-dependent DNase I hypersensitive site at position -1400 (DHS
      1400). BR-C encodes a family of transcription factors, and we show here that at
      least three BR-C protein isoforms--Z1, Z2, and Z3--bind to the sequences around
      DHS-1400 in vitro. A DNase I footprinting assay reveals five protected regions,
      designated site 1 to site 5, each of which specifically associates with one or
      several BR-C protein isoforms. We also show that a 100 bp region overlapping site
      5, which binds all three isoforms in vitro, is required for hsp23 activity in
      vivo. The deletion of binding site 5 in a reporter gene construct reproduced the
      effect of the npr class mutations, that is, hsp23 is no longer expressed in any
      tissue tested except brain. Thus, BR-C regulates hsp23 expression via direct
      interaction of the predominant isoform with the distal regulatory element.

PMID- 11583937
TI  - Target of rapamycin (TOR) inhibition in renal transplantation: Clinical uses in
      various populations. Introduction.

PMID- 11583938
TI  - Cyclosporine elimination in the presence of TOR inhibitors: effects on renal
      function, acute rejection, and safety.
AB  - Sirolimus in combination with cyclosporine reduces the incidence of acute
      rejection in renal transplant recipients when administered in double- or triple
      therapy immunosuppressive regimens. Sirolimus administered as primary therapy has
      a beneficial effect on renal function, and the frequency of rejection episodes is
      similar to that of primary immunosuppression with cyclosporine. A strategy that
      may result in a more benign immunologic course with a substantially beneficial
      effect on renal function is to administer sirolimus and a calcineurin inhibitor
      early after transplantation, thereby promoting immunologic adaptation, and then
      to withdraw the calcineurin inhibitor at some point after transplantation to
      prevent nephrotoxicity. This article examines the results of this approach in
      recent studies that evaluated the effect of cyclosporine withdrawal on renal
      function, acute rejection, and safety in patients treated with sirolimus. Two
      open-label randomized trials of cyclosporine withdrawal were conducted in the
      United States, Canada, Europe, and Australia. In one of the studies, graft
      survival, patient survival, and the incidence of acute rejection at 6 months
      posttransplantation were not statistically significantly different between the
      patients receiving cyclosporine and the group that had undergone cyclosporine
      withdrawal. Furthermore, significantly better renal function was observed in the
      patients who underwent cyclosporine withdrawal compared with patients who
      continued to receive full-dose cyclosporine. These studies indicate that
      cyclosporine withdrawal has a beneficial effect on renal function without a
      significant increase in the incidence of acute rejection episodes.

PMID- 11583939
TI  - Safety and efficacy of TOR inhibitors and other immunosuppressive regimens in
      African-American renal transplant recipients.
AB  - African-American renal transplant recipients have higher rates of acute allograft
      rejection and lower rates of allograft survival compared with Caucasian patients,
      and these differences have not been eliminated by a new generation of potent
      immunosuppressive drugs. In particular, African-Americans tend to exhibit higher
      rejection rates after withdrawal of corticosteroid therapy. Based on promising
      early results using the combination of sirolimus and low-dose tacrolimus in
      liver, kidney-pancreas, and islet-cell transplant recipients, our center is
      conducting a pilot study of this immunosuppression regimen in African-American
      patients. As of April 2001, there has been only 1 acute rejection episode (2.8%)
      in this cohort. Long-term follow-up of these patients will be necessary to assess
      the benefits and risks of this regimen.

PMID- 11583940
TI  - Sirolimus and mycophenolate mofetil for calcineurin-free immunosuppression in
      renal transplant recipients.
AB  - Calcineurin inhibitors, such as cyclosporine and tacrolimus, have been available
      for almost 20 years. Although these drugs are highly effective and represent the
      mainstay of transplant immunosuppression, they are associated with acute and
      chronic nephrotoxicity. Acute nephrotoxicity, which occurs in the early period
      after transplantation, leads to a higher rate of dialysis, and chronic
      nephrotoxicity may eventually result in graft loss. Acute and chronic
      nephrotoxicity is becoming more common as the use of marginal kidneys for
      transplantation increases. Two recently available immunosuppressive agents,
      mycophenolate mofetil and sirolimus (rapamycin), have no nephrotoxicity. The use
      of these drugs in combination with other agents has led to the development of new
      paradigms of immunosuppressive therapy. This paper reviews the results of
      clinical trials that have investigated these new approaches to immunosuppression
      in renal transplant recipients.

PMID- 11583941
TI  - Safety and efficacy of TOR inhibitors in pediatric renal transplant recipients.
AB  - Information about the pharmacokinetics, safety, and efficacy of target of
      rapamycin (TOR) inhibitors, such as sirolimus and everolimus, in pediatric renal
      transplant recipients is limited. In an ascending single-dose pharmacokinetic
      study of sirolimus in pediatric dialysis patients, no clinically significant
      association was observed between patient age and absorption of sirolimus from the
      gastrointestinal tract. However, young pediatric patients (5 to 11 years of age)
      exhibited significantly greater apparent oral clearances, suggesting that
      pediatric patients require slightly higher doses than do adults when adjusted for
      body weight or surface area. Similarly, in studies performed in pediatric renal
      transplant recipients, the half-life of sirolimus was shorter and the clearance
      was greater in younger patients. On the other hand, in single-dose
      pharmacokinetic studies of everolimus, the apparent clearance was reduced in
      pediatric renal transplant recipients compared with clearance in adults. This
      reduced clearance was attributed to a smaller apparent volume of distribution in
      pediatric patients, rather than to a difference in terminal half-life. This
      suggested that, although the adult 12-hour dosing interval was appropriate for
      pediatric patients, they would require reduced dosing based on body size compared
      with adults. In a large trial (N = 719) of sirolimus versus azathioprine in
      combination with cyclosporine microemulsion and prednisone, 6 pediatric patients
      (13 to 18 years of age) received sirolimus at 2 mg/d, 3 received sirolimus at 5
      mg/d, and 3 received azathioprine. Seven of the nine patients who received
      sirolimus experienced no rejection episodes. Six infectious episodes occurred in
      the 6 patients receiving sirolimus at 2 mg/d, 10 episodes occurred in the 3
      patients receiving sirolimus at 5 mg/d, and 8 episodes occurred in the 3 patients
      receiving azathioprine. At 6 months after transplantation, renal function was
      similar in all 3 groups, although there was a statistically nonsignificant
      increase in the group receiving sirolimus at 5 mg/d. The mean cholesterol and
      triglyceride levels were generally comparable in all 3 groups. TOR inhibitors are
      promising agents for the prevention of graft rejection in pediatric renal
      transplant recipients, but more pharmacokinetic data are required to assess the
      optimal dosing regimens in this population. In addition, further data are needed
      on the efficacy and safety of TOR inhibitors in combination with other agents in
      pediatric transplantation recipients to best assess the role of TOR inhibition in
      corticosteroid and/or calcineurin inhibitor-sparing regimens.

PMID- 11583944
TI  - Transforming growth factor-beta, basement membrane, and epithelial-mesenchymal
      transdifferentiation: implications for fibrosis in kidney disease.

PMID- 11583945
TI  - Anaplastic and atypical meningiomas express high levels of Fas and undergo
      apoptosis in response to Fas ligation.
AB  - In this study we characterized the expression of Fas and Fas ligand in different
      types of meningiomas and examined the effect of Fas ligation on the death of
      meningioma cells in culture. Using Western blot analysis, we found that extracts
      derived from anaplastic and atypical meningiomas expressed high levels of Fas,
      whereas benign meningiomas did not express detectable levels of this protein. All
      of the meningiomas examined expressed low levels of Fas ligand. Cultures of
      anaplastic meningiomas also expressed Fas and treatment of these cells with anti
      Fas antibody induced cell death. The results of this study indicate that Fas is
      preferentially expressed in atypical and anaplastic meningiomas and suggest that
      it is involved in the increased apoptosis observed in these tumors.

PMID- 11583946
TI  - Molecular signatures of sepsis: multiorgan gene expression profiles of systemic
      inflammation.
AB  - During sepsis the host's system-wide response to microbial invasion seems
      dysregulated. Here we explore the diverse multiorgan transcriptional programs
      activated during systemic inflammation in a cecal ligation/puncture model of
      sepsis in rats. Using DNA microarrays representing 7398 genes, we examined the
      temporal sequence of sepsis-induced gene expression patterns in major organ
      systems including lung, liver, kidney, thymus, spleen, and brain. Although genes
      known to be associated with systemic inflammation were identified by our global
      transcript analysis, many genes and expressed sequence tags not previously linked
      to the septic response were also elucidated. Taken together, our results suggest
      activation of a highly complex transcriptional response in individual organs of
      the septic animal. Several overlying themes emerged from our genome-scale
      analysis that includes 1) the sepsis response elicited gene expression profiles
      that were either organ-specific, common to more than one organ, or distinctly
      opposite in some organs; 2) the brain is protected from sepsis-induced gene
      activation relative to other organs; 3) the thymus and spleen have an interesting
      cohort of genes with opposing gene expression patterns; 4) genes with
      proinflammatory effects were often balanced by genes with anti-inflammatory
      effects (eg, interleukin-1beta/decoy receptor, xanthine oxidase/superoxide
      dismutase, Ca2+-dependent PLA2/Ca2+-independent PLA2); and 5) differential gene
      expression was observed in proteins responsible for preventing tissue injury and
      promoting homeostasis including anti-proteases (TIMP-1, Cpi-26), oxidant
      neutralizing enzymes (metallothionein), cytokine decoy receptors (interleukin
      1RII), and tissue/vascular permeability factors (aquaporin 5, vascular
      endothelial growth factor). This global perspective of the sepsis response should
      provide a molecular framework for future research into the pathophysiology of
      systemic inflammation. Understanding, on a genome scale, how an organism responds
      to infection, may facilitate the development of enhanced detection and treatment
      modalities for sepsis.

PMID- 11583947
TI  - Detection and typing of human papillomavirus DNA in penile carcinoma: evidence
      for multiple independent pathways of penile carcinogenesis.
AB  - To clarify the role of human papillomavirus (HPV) in penile cancer we evaluated
      the prevalence of HPV DNA in different histological subtypes of penile carcinoma,
      dysplasia, and condyloma using a novel, sensitive SPF10 HPV polymerase chain
      reaction assay and a novel genotyping line probe assay, allowing simultaneous
      identification of 25 different HPV types. Formalin-fixed, paraffin-embedded
      tissue samples were collected from the United States and Paraguay. HPV DNA was
      detected in 42% cases of penile carcinoma, 90% cases of dysplasia, and 100% cases
      of condyloma. There were significant differences in HPV prevalence in different
      histological cancer subtypes. Although keratinizing squamous cell carcinoma and
      verrucous carcinoma were positive for HPV DNA in only 34.9 and 33.3% of cases,
      respectively, HPV DNA was detected in 80% of basaloid and 100% of warty tumor
      subtypes. There was no significant difference in HPV prevalence between cases
      from Paraguay and the United States. In conclusion, the overall prevalence of HPV
      DNA in penile carcinoma (42%) is lower than that in cervical carcinoma
      (approximately 100%) and similar to vulvar carcinoma (approximately 50%). In
      addition, specific histological subtypes of penile cancer--basaloid and warty-
      are consistently associated with HPV, however, only a subset of keratinizing and
      verrucous penile carcinomas is positive for HPV DNA, and thus these two tumor
      groups seem to develop along different pathogenetic pathways.

PMID- 11583948
TI  - In vivo expression of major histocompatibility complex molecules on
      oligodendrocytes and neurons during viral infection.
AB  - Demyelination in multiple sclerosis and in animal models is associated with
      infiltrating CD8+ and CD4+ T cells. Although oligodendrocytes and axons are
      damaged in these diseases, the roles T cells play in the demyelination process
      are not completely understood. Antigen-specific CD8+ T cell lysis of target cells
      is dependent on interactions between the T cell receptor and major
      histocompatibility complex (MHC) class I-peptide complexes on the target cell. In
      the normal central nervous system, expression of MHC molecules is very low but
      often increases during inflammation. We set out to precisely define which central
      nervous system cells express MHC molecules in vivo during infection with a strain
      of murine hepatitis virus that causes a chronic, inflammatory demyelinating
      disease. Using double immunofluorescence labeling, we show that during acute
      infection with murine hepatitis virus, MHC class I is expressed in vivo by
      oligodendrocytes, neurons, microglia, and endothelia, and MHC class II is
      expressed only by microglia. These data indicate that oligodendrocytes and
      neurons have the potential to present antigen to T cells and thus be damaged by
      direct antigen-specific interactions with CD8+ T lymphocytes.

PMID- 11583949
TI  - RNF4 is a growth inhibitor expressed in germ cells but not in human testicular
      tumors.
AB  - The RING-finger protein RNF4 modulates both steroid-receptor-dependent and basal
      transcription and interacts with a variety of nuclear proteins involved in cell
      growth control. RNF4 is expressed at very high levels in testis and at much lower
      levels in several other tissues. We show that in germ cells RNF4 expression is
      strongly modulated during progression of spermatogonia to spermatids, with a peak
      in spermatocytes. Analysis of human testicular germ cell tumors shows that RNF4
      is not expressed in all tumors analyzed including seminomas, the highly malignant
      embryonal carcinomas, yolk sac, and mixed germ cell tumors. We also show that the
      ectopically expressed RNF4 gene inhibits cell proliferation of both somatic and
      germ cell tumor-derived cells. Mutation of critical cysteine residues in the RING
      finger domain abolished the RNF4 growth inhibition activity. Our results suggest
      that the lack of RNF4 expression may play a role in the progression of testicular
      tumors.

PMID- 11583950
TI  - Organ-specific molecular classification of primary lung, colon, and ovarian
      adenocarcinomas using gene expression profiles.
AB  - Molecular classification of tumors based on their gene expression profiles
      promises to significantly refine diagnosis and management of cancer patients. The
      establishment of organ-specific gene expression patterns represents a crucial
      first step in the clinical application of the molecular approach. Here, we report
      on the gene expression profiles of 154 primary adenocarcinomas of the lung,
      colon, and ovary. Using high-density oligonucleotide arrays with 7129 gene probe
      sets, comprehensive gene expression profiles of 57 lung, 51 colon, and 46 ovary
      adenocarcinomas were generated and subjected to principle component analysis and
      to a cross-validated prediction analysis using nearest neighbor classification.
      These statistical analyses resulted in the classification of 152 of 154 of the
      adenocarcinomas in an organ-specific manner and identified genes expressed in a
      putative tissue-specific manner for each tumor type. Furthermore, two tumors were
      identified, one in the colon group and another in the ovarian group, that did not
      conform to their respective organ-specific cohorts. Investigation of these
      outlier tumors by immunohistochemical profiling revealed the ovarian tumor was
      consistent with a metastatic adenocarcinoma of colonic origin and the colonic
      tumor was a pleomorphic mesenchymal tumor, probably a leiomyosarcoma, rather than
      an epithelial tumor. Our results demonstrate the ability of gene expression
      profiles to classify tumors and suggest that determination of organ-specific gene
      expression profiles will play a significant role in a wide variety of clinical
      settings, including molecular diagnosis and classification.

PMID- 11583951
TI  - Development of a yeast stop codon assay readily and generally applicable to human
      genes.
AB  - We established a yeast-based method to screen chain-terminating mutations that is
      readily applicable to any gene of interest. Based on the finding that 18- to 24
      base-long homologous sequences are sufficient for gap repair in vivo in yeast, we
      used a strategy to amplify a test-gene fragment with addition of 24-bp sequences
      homologous to both cut-ends of a yeast expression vector, pMT18. After co
      transformation with the amplified fragment and the linearized pMT18, each yeast
      (Saccharomyces cerevisiae) cell automatically forms a single-copy circular
      plasmid (because of CEN/ARS), which expresses a test-gene::ADE2 chimera protein.
      When the reading frame of the test-gene contains a nonsense or frameshift
      mutation, truncation of the chimera protein results in lack of ADE2 activity,
      leading to formation of a red colony. By using a nested polymerase chain reaction
      using proofreading Pfu polymerase to ensure specificity of the product, the assay
      achieved a low background (false positivity). We applied the assay to BRCA1, APC,
      hMSH6, and E-cadherin genes, and successfully detected mutations in mRNA and
      genomic DNA. Because this method--universal stop codon assay--requires only 4 to
      5 days to screen a number of samples for any target gene, it may serve as a high
      throughput screening system of general utility for chain-terminating mutations
      that are most prevalent in human genetic diseases.

PMID- 11583952
TI  - Persistent p53 mutations in single cells from normal human skin.
AB  - Epidermal clones of p53-mutated keratinocytes are abundant in chronically sun
      exposed skin and may play an important role in early development of skin cancer.
      Advanced laser capture microdissection enables genetic analysis of targeted cells
      from tissue sections without contamination from neighboring cells. In this study
      p53 gene mutations were characterized in single cells from normal, chronically
      sun-exposed skin. Biopsies were obtained from skin subjected to daily summer sun
      and skin totally protected from the sun by blue denim fabric. Using laser capture
      microdissection, 172 single-cell samples were retrieved from four biopsies and
      analyzed using single-cell polymerase chain reaction and direct DNA sequencing. A
      total of 14 different mutations were identified in 26 of 99 keratinocytes from
      which the p53 gene could be amplified. Mutations displayed a typical UV signature
      and were detected in both scattered keratinocytes and in a small cluster of p53
      immunoreactive keratinocytes. This minute epidermal p53 clone had a diameter of
      10 to 15 basal cells. Two missense mutations were found in all layers of
      epidermis within the p53 clone. The presented data show that p53 mutations are
      common in normal skin and that a clone of keratinocytes with a mutated p53 gene
      prevailed despite 2 months of total protection from ultraviolet light.

PMID- 11583953
TI  - Altered extracellular matrix remodeling and angiogenesis in sponge granulomas of
      thrombospondin 2-null mice.
AB  - The matricellular angiogenesis inhibitor, thrombospondin (TSP) 2, has been shown
      to be an important modulator of wound healing and the foreign body response.
      Specifically, TSP2-null mice display improved healing with minimal scarring and
      form well-vascularized foreign body capsules. In this study we performed
      subcutaneous implantation of sponges and investigated the resulting angiogenic
      and fibrogenic responses. Histological and immunohistochemical analysis of
      sponges, excised at 7, 14, and 21 days after implantation, revealed significant
      differences between TSP2-null and wild-type mice. Most notably, TSP2-null mice
      exhibited increased angiogenesis and fibrotic encapsulation of the sponge.
      However, invasion of dense tissue was compromised, even though its overall
      density was increased. Furthermore, histomorphometry and biochemical assays
      demonstrated a significant increase in the extracellular distribution of matrix
      metalloproteinase (MMP) 2, but no change in the levels of active transforming
      growth factor-beta(1). The alterations in neovascularization, dense tissue
      invasion, and MMP2 in TSP2-null mice coincided with the deposition of TSP2 in the
      extracellular matrix of wild-type animals. These observations support the
      proposed role of TSP2 as a modulator of angiogenesis and matrix remodeling during
      tissue repair. In addition, they provide in vivo evidence for a newly proposed
      function of TSP2 as a modulator of extracellular MMP2 levels.

PMID- 11583954
TI  - Skeletal muscle fibers express major histocompatibility complex class II antigens
      independently of inflammatory infiltrates in inflammatory myopathies.
AB  - The aim of our study was to address the question of whether muscle fibers express
      major histocompatibility complex (MHC) class II in inflammatory myopathies. For
      this purpose we performed a systematic study of MHC class II antigen expression
      on muscle fiber membranes in muscle tissue from polymyositis and dermatomyositis
      patients in various stages of disease activity. Thirty-two patients with
      classical clinical signs of myositis were divided into subgroups depending on
      duration of clinical signs of myositis and presence or absence of inflammatory
      infiltrates in muscle tissue. Immunohistochemistry as well as double
      immunofluorescence stainings were used to identify the presence of MHC class II
      in muscle tissue. MHC class I was included for comparison. Quantification of
      positive staining was performed using an image analysis system in addition to
      evaluation by manual microscopic scoring and laser confocal microscopy. It was
      demonstrated that a significant proportion of skeletal muscle fibers in
      inflammatory myopathies express MHC class II as well as MHC class I and that MHC
      antigen expression is independent of the inflammatory cell infiltration.
      Furthermore, there were no differences in staining pattern between polymyositis
      and dermatomyositis patients. Our results indicate that MHC class II and MHC
      class I molecules may be involved in initiating and maintaining the pathological
      condition in myositis rather than only being a consequence of a preceding local
      inflammation.

PMID- 11583955
TI  - Hepatocyte growth factor/scatter factor released during peritonitis is active on
      mesothelial cells.
AB  - Peritonitis causes mesothelial detachment that may result in persistent
      peritoneal denudation and fibrosis. We investigated whether hepatocyte growth
      factor (HGF), a scatter factor that induces detachment from substrate and
      fibroblastic transformation of several cell types, is produced during peritonitis
      and is active on mesothelial cells. We studied 18 patients on peritoneal
      dialysis, 9 uncomplicated, 9 with peritonitis. HGF was measured in serum,
      peritoneal fluid, and supernatant of peripheral blood mononuclear cells and
      peritoneal mononuclear cells. Primary culture of human peritoneal mesothelial
      cells and the human mesothelial cell line MeT-5A were conditioned with
      recombinant HGF, serum, and peritoneal fluid. HGF levels were significantly
      higher in serum and peritoneal fluid of peritonitic than uncomplicated patients.
      Mononuclear cells of peritonitic patients produced more HGF than cells of
      uncomplicated patients. Recombinant HGF, serum, and peritoneal fluid of
      peritonitic patients caused mesothelial cell growth, detachment, transformation
      from epithelial to fibroblast-like shape, overexpression of vimentin, and
      synthesis of type I and III collagen. In conclusion, HGF released during
      peritonitis causes a change in mesothelial cell phenotype and function. HGF may
      affect the healing process facilitating repair through mesothelial cell growth,
      but may contribute to peritoneal fibrosis inducing cell detachment with
      mesothelial denudation and collagen synthesis.

PMID- 11583956
TI  - No direct role for Epstein-Barr virus in American hepatocellular carcinoma.
AB  - Epstein-Barr virus (EBV) was recently linked to hepatocellular carcinogenesis in
      Japanese patients. It is not clear whether EBV infection is also associated with
      hepatocellular carcinoma (HCC) occurring in American patients. We studied 41
      cases of HCC from the Los Angeles area for evidence of EBV infection by in situ
      hybridization, immunohistochemistry, and polymerase chain reaction methods. Of 41
      cases, 16 were seropositive for hepatitis B virus surface antigen (39%), 9 of 29
      tested were seropositive for hepatitis C virus antibody (31%); in total, 22 cases
      were seropositive for hepatitis B virus and/or hepatitis C virus (53%). Of 41
      cases, 1 was positive for EBV-encoded small nonpolyadenylated RNA (EBER)-1 (2%)
      by in situ hybridization. By immunohistochemistry, two cases were positive for
      EBV nuclear antigen (EBNA)-1 (5%), one was positive for the transactivating
      immediate early BZLF1 (ZEBRA) (2%), and none was positive for latent membrane
      protein-1. None of the 41 cases was positive for latent membrane protein-1 and
      EBV nuclear antigen (EBNA)-4 DNAs by polymerase chain reaction assay. All four
      positive cases showed rare EBER-1-, ZEBRA-, or EBNA-1- positive cells (<0.1%); in
      none of these cases was there expression of any other EBV viral genes. In the one
      case each that was positive for EBER-1 and ZEBRA, both of which occurred in
      patients of non-Asian ethnicity, the staining was limited to infiltrating small
      lymphocytes, and tumor cells were negative. In the two cases that were positive
      for EBNA-1, both of which occurred in patients of Asian ethnicity, the staining
      was limited to tumor cells, and infiltrating small lymphocytes were negative. Our
      study indicates that rare cases of American HCC may contain EBV-infected cells,
      but it is unlikely that EBV plays a major role in the carcinogenesis of HCC.

PMID- 11583957
TI  - Comprehensive analysis of SMAD4 mutations and protein expression in juvenile
      polyposis: evidence for a distinct genetic pathway and polyp morphology in SMAD4
      mutation carriers.
AB  - Juvenile polyposis syndrome (JPS; OMIM 174900) is a rare disorder which is
      characterized by the presence of hamartomatous polyps throughout the
      gastrointestinal tract and an increased risk of gastrointestinal malignancy.
      Mutations of the SMAD4 gene on chromosome 18q21.1 have been shown to cause a
      subset of JPS cases, with estimates ranging from 20% to >50%. Characterization of
      the genes that cause the remainder of JPS cases relies on the certainty that
      SMAD4 is not the causative gene. We have undertaken a comprehensive analysis of
      germline SMAD4 mutations in a cohort of JPS patients to define the spectrum of
      mutations that cause JPS. We have analyzed a series of polyps from these patients
      for SMAD4 protein expression. We have also performed a blinded assessment of
      polyp material to look for morphological differences between polyps from patients
      with and without a germline SMAD4 mutation. The results indicate that almost all
      germline SMAD4 mutations are readily detectable by screening genomic DNA using
      polymerase chain reaction-based methods; SMAD4 can be excluded as the causative
      gene in the majority of our JPS cohort. Loss of SMAD4 expression occurs in most
      polyps from SMAD4 mutation carriers, even those with missense germline mutations.
      SMAD4 loss in polyps is, however, not a feature of cases that are not caused by
      SMAD4 mutations, indicating that these polyps develop along a SMAD4-independent
      pathway. The morphology of polyps from SMAD4 mutation carriers is subtly
      different from other JPS polyps, notably including a more prominent epithelial
      component in the former.

PMID- 11583958
TI  - Reactive oxygen intermediates induce monocyte chemotactic protein-1 in vascular
      endothelium after brief ischemia.
AB  - Chemokine expression is associated with reperfusion of infarcted myocardium in
      the setting of tissue necrosis, intense inflammation, and inflammatory cytokine
      release. The specific synthesis of monocyte chemotactic protein (MCP)-1 mRNA by
      cardiac venules in reperfused infarcts corresponded to the region where
      leukocytes normally localize. MCP-1 could be induced by exogenous tumor necrosis
      factor (TNF)-alpha or by postischemic cardiac lymph containing TNF-alpha.
      However, the release of TNF-alpha during early reperfusion did not explain the
      venular localization of MCP-1 induction. To better understand the factors
      mediating MCP-1 induction, we examined the role of ischemia/reperfusion in a
      model of brief coronary occlusion in which no necrosis or inflammatory response
      is seen. Adult mongrel dogs were subjected to 15 minutes of coronary occlusion
      and 5 hours of reperfusion. Ribonuclease protection assay revealed up-regulation
      of MCP-1 mRNA only in ischemic segments of reperfused canine myocardium.
      Pretreatment with the reactive oxygen scavenger N-(2-mercaptopropionyl)-glycine
      completely inhibited MCP-1 induction. In situ hybridization localized MCP-1
      message to small venular endothelium in ischemic areas without myocyte necrosis.
      Gel shift analysis of nuclear extracts from the ischemic area showed enhanced DNA
      binding of the transcription factors AP-1 and nuclear factor (NF)-kappaB, crucial
      for MCP-1 expression, in ischemic myocardial regions. Immunohistochemical
      staining demonstrated reperfusion-dependent nuclear translocation of c-Jun and NF
      kappaB (p65) in small venular endothelium, only in the ischemic regions of the
      myocardium, that was inhibited by N-(2-mercaptopropionyl)-glycine. In vitro,
      treatment of cultured canine jugular vein endothelial cells with the reactive
      oxygen intermediate H2O2 induced a concentration-dependent increase in MCP-1 mRNA
      levels, which was inhibited by the antioxidant N-acetyl-L-cysteine, a precursor
      of glutathione, but not pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB
      and activator of AP-1. In contrast to our studies with infarction, incubation of
      canine jugular vein endothelial cells with postischemic cardiac lymph did not
      induce MCP-1 mRNA expression suggesting the absence of cytokine-mediated MCP-1
      induction after a sublethal ischemic period. These results suggest that reactive
      oxygen intermediate generation, after a brief ischemic episode, is capable of
      inducing MCP-1 expression in venular endothelium through AP-1 and NF-kappaB.
      Short periods of ischemia/reperfusion, insufficient to produce a myocardial
      infarction, induce MCP-1 expression, potentially mediating angiogenesis in the
      ischemic noninfarcted heart.

PMID- 11583959
TI  - Renal fibrosis: collagen composition and assembly regulates epithelial
      mesenchymal transdifferentiation.
AB  - Type IV collagen is a major component of basement membranes and it provides
      structural and functional support to various cell types. Type IV collagen exists
      in a highly complex suprastructure form and recent studies implicate that
      protomer (the trimeric building unit of type IV collagen) assembly is mediated by
      the NC1 domain present in the C-terminus of each collagen alpha-chain
      polypeptide. Here we show that type IV collagen contributes to the maintenance of
      the epithelial phenotype of proximal tubular epithelial cells, whereas type I
      collagen promotes epithelial-to-mesenchymal transdifferentiation (EMT). In
      addition, the recombinant human alpha1NC1 domain inhibits assembly of type IV
      collagen NC1 hexamers and potentially disrupts the deposition of type IV
      collagen, facilitating EMT in vitro. Inhibition of type IV collagen assembly by
      the alpha1NC1 domain up-regulates the production of transforming growth factor
      beta1 in proximal tubular epithelial cells, an inducer of EMT. These results
      strongly suggest that basement membrane architecture is pivotal for the
      maintenance of epithelial phenotype and that changes in basement membrane
      architecture potentially lead to up-regulation of transforming growth factor
      beta1, which contributes to EMT during renal fibrosis.

PMID- 11583960
TI  - Stem cell properties and repopulation of the rat liver by fetal liver epithelial
      progenitor cells.
AB  - The potential of embryonal day (ED) 14 fetal liver epithelial progenitor (FLEP)
      cells from Fischer (F)344 rats to repopulate the normal and retrorsine-treated
      liver was studied throughout a 6-month period in syngeneic dipeptidyl peptidase
      IV (DPPIV-) mutant F344 rats. In normal liver, FLEP cells formed: 1) hepatocytic
      clusters ranging in size up to approximately 800 to 1000 cells; 2) bile duct
      structures connected to pre-existing host bile ducts; and 3) mixed clusters
      containing both hepatocytes and bile duct epithelial cells. Liver repopulation
      after 6 months was moderate (5 to 10%). In retrorsine-treated liver, transplanted
      cells formed large multilobular structures containing both parenchymal and bile
      duct cells and liver repopulation was extensive (60 to 80%). When the
      repopulating capacity of ED 14 FLEP cells transplanted into normal liver was
      compared to adult hepatocytes, three important differences were noted: 1) FLEP
      cells continued to proliferate at 6 months after transplantation, whereas adult
      hepatocytes ceased proliferation within the first month; 2) both the number and
      size of clusters derived from FLEP cells gradually increased throughout time but
      decreased throughout time with transplanted mature hepatocytes; and 3) FLEP cells
      differentiated into hepatocytes when engrafted into the liver parenchyma and into
      bile epithelial cells when engrafted in the vicinity of the host bile ducts,
      whereas adult hepatocytes did not form bile duct structures. Finally, after
      transplantation of ED 14 FLEP cells, new clusters of DPPIV+ cells appeared after
      4 to 6 months, suggesting reseeding of the liver by transplanted cells. This
      study represents the first report with an isolated fetal liver epithelial cell
      fraction in which the cells exhibit properties of tissue-determined stem cells
      after their transplantation into normal adult liver; namely, bipotency and
      continued proliferation long after their transplantation.

PMID- 11583961
TI  - Aortic valve endothelial cells undergo transforming growth factor-beta-mediated
      and non-transforming growth factor-beta-mediated transdifferentiation in vitro.
AB  - Cardiac valves arise from endocardial cushions, specialized regions of the
      developing heart that are formed by an endothelial-to-mesenchymal cell
      transdifferentiation. Whether and to what extent this transdifferentiation is
      retained in mature heart valves is unknown. Herein we show that endothelial cells
      from mature valves can transdifferentiate to a mesenchymal phenotype. Using
      induction of alpha-smooth muscle actin (alpha-SMA), an established marker for
      this process, two distinct pathways of transdifferentiation were identified in
      clonally derived endothelial cell populations isolated from ovine aortic valve
      leaflets. alpha-SMA expression was induced by culturing clonal endothelial cells
      in medium containing either transforming growth factor-beta or low levels of
      serum and no basic fibroblast growth factor. Cells induced to express alpha-SMA
      exhibited markedly increased migration in response to platelet-derived growth
      factor-BB, consistent with a mesenchymal phenotype. A population of the
      differentiated cells co-expressed CD31, an endothelial marker, along with alpha
      SMA, as seen by double-label immunofluorescence. Similarly, this co-expression of
      endothelial markers and alpha-SMA was detected in a subpopulation of cells in
      frozen sections of aortic valves, suggesting the transdifferentiation may occur
      in vivo. Hence, the clonal populations of valvular endothelial cells described
      here provide a powerful in vitro model for dissecting molecular events that
      regulate valvular endothelium.

PMID- 11583962
TI  - Persistent increase in chromosome instability in lung cancer: possible indirect
      involvement of p53 inactivation.
AB  - Karyotype and fluorescence in situ hybridization analyses have demonstrated the
      frequent presence of an altered static state of the number of chromosomes (ie,
      aneuploidy) in lung cancer, but it has not been directly established whether
      aneuploidy is in fact associated with a persistent increase in the rate of
      chromosomal losses and gains (ie, chromosome instability, or CIN). The study
      presented here used a panel of 10 lung cancer cell lines to provide for the first
      time direct evidence that CIN is a common feature in lung cancer cell lines in
      association with the presence of significant aneuploidy. In addition, we found
      that the CIN phenotype correlates well with the presence of p53 mutations.
      However, human papilloma virus 16-E6-directed inactivation of p53 in a
      representative non-CIN lung cancer cell line did not result in the induction of
      CIN, at least up to the 25th generation, suggesting that inactivation of p53
      itself is unlikely to directly induce CIN in lung cancer cells. Interestingly,
      however, significant CIN could be induced in conjunction with the generation of
      aneuploid populations when the mitotic spindle formation was transiently
      abrogated in p53-inactivated cells. These results suggest that inactivation of
      p53 may allow lung cancer cells to go through an inappropriate second division
      cycle under certain forms of mitotic stresses, which would result in the
      induction of the CIN phenotype in conjunction with the generation of aneuploidy.

PMID- 11583963
TI  - Enhanced expression of endothelin B receptor at protein and gene levels in human
      cirrhotic liver.
AB  - Endothelin (ET) has been implicated in the regulation of hepatic microcirculation
      and development of portal hypertension. This study examined the localization of
      ETA receptor (ETAR) and ETB receptor (ETBR) in cirrhotic liver tissues from
      patients with hepatocellular carcinoma with hepatitis C-related cirrhosis, and
      normal liver samples from patients with metastatic liver carcinoma. Anti-ETAR and
      ETBR antibodies were used for immunohistochemistry and Western blot.
      Immunoelectron microscopy was conducted using immunoglobulin-gold and silver
      staining. For in situ hybridization (ISH), human ETAR and ETBR peptide nucleic
      acid probes were used with the catalyzed signal amplification system. In normal
      liver tissue, immunohistochemistry revealed that ETBR was predominantly expressed
      on hepatic sinusoidal lining cells, particularly on sinusoidal endothelial (SECs)
      and hepatic stellate cells (HSCs), and ETAR was scantily expressed. These
      findings were confirmed by Western blot and ISH. In cirrhotic liver tissue,
      overexpression of ETBR was demonstrated by Western blot and ISH. Morphometric
      analysis showed significant increase of ETBR expression on HSCs and SECs in
      cirrhotic liver, particularly on HSCs. ETAR expression was increased but remained
      low. Enhanced ETBR expression in cirrhosis may intensify the effect of endothelin
      on HSCs and increase hepatic microvascular tone.

PMID- 11583964
TI  - Increased expression of a nucleolar Nop5/Sik family member in metastatic melanoma
      cells: evidence for its role in nucleolar sizing and function.
AB  - F10 and BL6 cells of B16 mouse melanoma cells are metastatic after intravenous
      injection, but only BL6 cells can metastasize to lungs after subcutaneous
      injection. Differences in gene expression between the two cell lines were
      examined, and a greater expression of the Sik-similar protein (Sik-SP) gene was
      found in BL6 cells. Structurally, Sik-SP belongs to the nucleolar Nop5/Sik family
      whose members play central roles in ribosome biogenesis; however, the function of
      Sik-SP has not been examined. Cytology with green fluorescent protein-fused
      proteins showed that Sik-SP was localized to the nucleolus. To examine whether
      Sik-SP is involved in ribosome biogenesis, two parameters were measured:
      magnitude of ribosomal RNA synthesis per nucleus and magnitude of protein
      production from the same amount of mRNA of an exogenous luciferase gene. Both
      values and, in addition, nucleolar size were larger in COS-7 monkey kidney cells
      overexpressing Sik-SP and BL6 cells than in mock-transfected COS-7 and F10 cells,
      respectively. Sik-SP seemed to promote ribosome biogenesis in the nucleolus.
      Furthermore, the expression of Sik-SP seemed to confer a greater cell growth
      response to serum, because such a response was greater in BL6 cells and F10 cells
      overexpressing Sik-SP than in untreated and mock-transfected F10 cells. Sik-SP
      may render melanoma cells more competent to survive through augmenting the
      activity of nucleolus.

PMID- 11583965
TI  - Myosin XVA expression in the pituitary and in other neuroendocrine tissues and
      tumors.
AB  - The myosin superfamily of molecular motor proteins includes conventional myosins
      and several classes of unconventional myosins. Recent studies have characterized
      the human and mouse unconventional myosin XVA, which has a role in the formation
      and/or maintenance of the unique actin-rich structures of inner ear sensory hair
      cells. Myosin XVA is also highly expressed in human anterior pituitary cells. In
      this study we examined the distribution of myosin XVA protein and mRNA in normal
      and neoplastic human pituitaries and other neuroendocrine cells and tumors.
      Myosin XVA was expressed in all types of normal anterior pituitary cells and
      pituitary tumors and in other neuroendocrine cells and tumors including those of
      the adrenal medulla, parathyroid, and pancreatic islets. Most nonneuroendocrine
      tissues examined including liver cells were negative for myosin XVA protein and
      mRNA, although the distal and proximal tubules of normal kidneys showed moderate
      immunoreactivity for myosin XVA. Ultrastructural immunohistochemistry localized
      myosin XVA in association with secretory granules of human anterior pituitary
      cells and human pituitary tumors. These data suggest that in neuroendocrine cells
      myosin XVA may have a role in secretory granule movement and/or secretion.

PMID- 11583966
TI  - Direct thrombin inhibition reduces lung collagen, accumulation, and connective
      tissue growth factor mRNA levels in bleomycin-induced pulmonary fibrosis.
AB  - Dramatic activation of the coagulation cascade has been extensively documented
      for pulmonary fibrosis associated with acute and chronic lung injury. In addition
      to its role in hemostasis, thrombin exerts profibrotic effects via activation of
      the major thrombin receptor, protease-activated receptor-1. In this study, we
      examined the effect of the direct thrombin inhibitor, UK-156406 on fibroblast
      responses in vitro and on bleomycin-induced pulmonary fibrosis in rats. UK-156406
      significantly inhibited thrombin-induced fibroblast proliferation, procollagen
      production, and connective tissue growth factor (CTGF) mRNA levels when used at
      equimolar concentration to the protease. Thrombin levels in bronchoalveolar
      lavage fluid and expression of thrombin and protease-activated receptor-1 in lung
      tissue were increased after intratracheal instillation of bleomycin. The
      characteristic doubling in lung collagen in bleomycin-treated animals (38.4 +/-
      2.0 mg versus 17.1 +/- 1.4 mg, P < 0.01) was preceded by significant elevations
      in alpha1(I) procollagen and CTGF mRNA levels (3.0 +/- 0.4-fold and 6.3 +/- 0.4
      fold respectively, (P < 0.01), and total inflammatory cell number. UK-156406,
      administered at an anticoagulant dose, attenuated lung collagen accumulation in
      response to bleomycin by 35 +/- 12% (P < 0.05), inhibited alpha1(I) procollagen
      and CTGF mRNA levels by 50% and 35%, respectively (P < 0.05), but had no effect
      on inflammatory cell recruitment. This is the first report showing that direct
      thrombin inhibition abrogates lung collagen accumulation in bleomycin-induced
      pulmonary fibrosis.

PMID- 11583967
TI  - Suppression by apoptotic cells defines tumor necrosis factor-mediated induction
      of glomerular mesangial cell apoptosis by activated macrophages.
AB  - Activated macrophages (M(phi)) isolated from inflamed glomeruli or generated by
      interferon-gamma and lipopolysaccharide treatment in vitro induce glomerular
      mesangial cell apoptosis by hitherto incompletely understood mechanisms. In this
      report we demonstrate that nitric oxide-independent killing of co-cultured
      mesangial cells by interferon-gamma/lipopolysaccharide-activated M(phi) is
      suppressed by binding/ingestion of apoptotic cells and is mediated by tumor
      necrosis factor (TNF). Thus, soluble TNF receptor-1 significantly inhibited
      induction of mesangial cell apoptosis by 1) rodent M(phi) in the presence of
      nitric oxide synthase inhibitors or 2) human M(phi), both situations in which
      nitric oxide release was minimal. Furthermore, murine TNF knockout M(phi) were
      completely unable to induce mesangial cell apoptosis in the presence of nitric
      oxide synthase inhibitors. We conclude that TNF-restricted M(phi)-directed
      apoptosis of glomerular mesangial cells can be down-regulated by M(phi)
      binding/ingestion of apoptotic cells, suggesting a new mechanism for negative
      feedback regulation of M(phi) controls on resident cell number at inflamed sites.

PMID- 11583968
TI  - Tumor angiogenesis induced by granulocyte chemotactic protein-2 as a
      countercurrent principle.
AB  - Chemokine production by tumors is a well-known phenomenon, but its role in tumor
      biology remains debatable. Although intratumoral injection of granulocyte
      chemotactic protein-2 (GCP-2) had no effect on tumor parameters, needle-free
      stable expression of the chemokine resulted in enhanced tumor growth. It is shown
      here that tumors that express a potent form of GCP-2 induce a strong influx and
      activation of tumor-associated neutrophils. The production of GCP-2 leads to
      intratumoral expression of gelatinase B and advantage for tumor growth by
      increased angiogenesis. These results are in line with the countercurrent
      principle of chemokine action and support the notion that paraneoplastic
      expression of ELR-positive CXC chemokines has to be blocked rather than
      stimulated in cancer therapy.

PMID- 11583969
TI  - cDNA arrays and immunohistochemistry identification of CD10/CALLA expression in
      hepatocellular carcinoma.
AB  - The histological diagnosis of hepatocellular carcinoma (HCC) can be complicated
      by difficulty in differentiation from cholangiocarcinoma and metastatic
      carcinoma. Immunohistochemical stains currently in use are suboptimal in terms of
      specificity and sensitivity. Using cDNA array analysis for differential gene
      expression, we demonstrated a significant increase in mRNA expression level of
      CD10/CALLA, a type 2 cell-surface metalloproteinase, in HCC, which was
      subsequently confirmed by reverse transcriptase-polymerase chain reaction and
      Western blotting analysis. To test the possibility of using CD10/CALLA as a
      diagnostic marker for HCC, various intrahepatic tumors were studied
      immunohistochemically using a monoclonal antibody for CD10. A characteristic
      canalicular-staining pattern was observed in normal hepatocytes and at the apical
      surface of bile duct epithelial cells. The canalicular expression of CD10 was
      identified in 9 of 15 HCCs examined (60%), whereas 10 cholangiocarcinomas and 8
      of 9 metastatic carcinomas lacked this staining. In three of the six HCCs
      negative for CD10, the surrounding nonneoplastic liver tissue was also negative,
      suggesting fixation-associated loss of immunoreactivity. Six HCCs had stronger
      CD10 staining in tumor cells when compared to the surrounding nonneoplastic
      tissue. Three cases of benign bile duct adenomas also expressed CD10 at the
      luminal aspect. One of the MCs showed a diffuse, cytoplasmic staining for CD10, a
      pattern readily distinguishable from that of HCC. A panel of other
      immunohistochemical markers were also studied for comparison, including
      polyclonal anti-carcinoembryonic antigen, cytokeratin (CK) 7, CK20, and alpha
      fetoprotein. Our results demonstrate that cDNA arrays can be effectively used to
      identify new diagnostic markers, and that CD10 is a reliable marker for
      identifying HCC, particularly when used in conjunction with a panel of
      immunohistochemical markers (polyclonal anti-carcinoembryonic antigen, CK7, CK20,
      and alpha-fetoprotein) and in the distinction from cholangiocarcinoma.

PMID- 11583970
TI  - Tumor-derived granulocyte-macrophage colony-stimulating factor and granulocyte
      colony-stimulating factor prolong the survival of neutrophils infiltrating
      bronchoalveolar subtype pulmonary adenocarcinoma.
AB  - We evaluated the role of the tumor environment in the regulation of apoptosis of
      tumor-infiltrating neutrophils, the number of which correlates negatively with
      outcome, in patients with adenocarcinoma of the bronchioloalveolar (BAC) subtype.
      We examined three different parameters of apoptosis, namely morphological aspect,
      annexin-V expression, and DNA fragmentation. Bronchoalveolar lavage fluid (BALF)
      supernatants from patients with BAC significantly inhibited the 24-hour
      spontaneous apoptosis of normal peripheral blood neutrophils in vitro compared to
      BALF supernatants from control patients (64 +/- 4% versus 90 +/- 2% measured by
      annexin-V flow cytometry, P = 0.04). The alveolar neutrophil count correlated
      positively with the granulocyte colony-stimulating factor (G-CSF) and granulocyte
      macrophage colony-stimulating factor (GM-CSF) concentrations in the patient's
      BALF. Furthermore, neutralizing antibodies (Abs) against GM-CSF and G-CSF
      significantly inhibited BALF anti-apoptotic activity (15 to 40% and 34 to 63%
      inhibition, respectively), whereas neutralizing Abs against interleukin (IL)-8,
      IL-6, IL-1beta and tumor necrosis factor-alpha had no significant effect. In an
      attempt to identify the cell origin of anti-apoptotic cytokines, we tested in
      vitro the effect of BAC cells (A549 cell line and primary culture derived from a
      patient's BAC tumor) on the apoptosis of peripheral blood neutrophils. Cell-free
      supernatants from tumor cells did not inhibit neutrophil apoptosis. In contrast,
      cell-free supernatants from tumor cells previously exposed to conditioned media
      from peripheral blood mononuclear cells and alveolar macrophages significantly
      inhibited spontaneous neutrophil apoptosis. This inhibition was partially lifted
      when conditioned media from mononuclear cells were previously treated with Abs
      against IL-1beta and tumor necrosis factor-alpha. As in vivo, neutralizing Abs
      against GM-CSF significantly inhibited the anti-apoptotic activity of cell
      culture supernatants, and combination with Abs against G-CSF had an additive
      effect. In vivo, GM-CSF and G-CSF were strongly expressed by tumor cells and
      moderately or not expressed by the normal epithelium, as assessed by
      immunohistochemical studies. These findings demonstrate that the tumor
      environment generates local conditions that prolong alveolar neutrophil survival
      through the production of soluble factors, thereby contributing to the
      persistence of the neutrophil alveolitis observed in BAC.

PMID- 11583971
TI  - Cytokine modulation of liver annexin 1 expression during experimental
      endotoxemia.
AB  - Annexin 1 (ANXA1) is a calcium-binding protein endowed with anti-inflammatory
      properties. Using an extra-hepatic system, we showed that interleukin (IL)-6
      regulates ANXA1 expression at the transcriptional level. The purpose of this
      study was to determine whether ANXA1 synthesis was modulated by IL-6 during
      experimental inflammation. We have compared liver ANXA1 expression during
      systemic and localized inflammatory reaction, using lipopolysaccharide (LPS) and
      turpentine. LPS treatment strongly induced ANXA1 expression in the liver of wild
      type (WT) animals (+600%) whereas a modest increase (+60%) was measured in IL-6
      knockout (KO) animals. Turpentine treatment did not affect the expression of
      ANXA1 in either animal type. LPS enhanced serum corticosteroid levels equally in
      WT and IL-6 KO mice, whereas higher tumor necrosis factor (TNF)-alpha and IL
      1beta levels were released in IL-6 KO animals. Injection of mouse recombinant IL
      6 to IL-6 KO animals before LPS or TNF-alpha challenge, replenished ANXA1 liver
      synthesis to that of WT animals. Exogenous ANXA1 but not ANXA5, administered to
      IL-6 KO mice before LPS challenge inhibited TNF-alpha release. We propose that
      ANXA1 acts as a novel acute phase protein, which is controlled in the liver by
      TNF-alpha and IL-6, and which may contribute to the resolution of systemic
      endotoxemia through a negative feedback on TNF-alpha release.

PMID- 11583972
TI  - Plasma apolipoprotein(a) co-deposits with fibrin in inflammatory arthritic
      joints.
AB  - Extravascular coagulation and diminished fibrinolysis are processes that
      contribute to the pathology of both inflammatory arthritis and atherosclerosis.
      We hypothesized that, given its homology with plasminogen, apolipoprotein (apo)
      (a), the distinctive glycoprotein of the atherogenic lipoprotein (Lp) (a), may be
      equally implicated in inflammatory arthritis. We detected the presence of apo(a)
      as part of Lp(a) in human arthritic synovial fluid. The abundance of apo(a) in
      synovial fluid rose in proportion to plasma apo(a) levels and was higher in
      inflammatory arthritides than in osteoarthritis. In addition, apo(a)
      immunoreactive material, but not apo(a) transcripts, was detected in inflammatory
      arthritic synovial tissues. These data indicated that synovial fluid apo(a)
      originates from circulating Lp(a) and that diffusion of Lp(a) through synovial
      tissue is facilitated in inflammatory types of arthritis. In synovial tissues,
      apo(a) co-localized with fibrin. These observations could be reproduced in a
      model of antigen-induced arthritis, using transgenic mice expressing human Lp(a).
      Although in this mouse model the presence of apo(a) did not change the severity
      of arthritis, the co-localization of apo(a) with fibrin in synovial tissue
      suggests that, in humans, apo(a) may modulate locally the fibrinolytic activity
      and may thus contribute to the persistence of intra-articular fibrin in
      inflammatory arthritis.

PMID- 11583973
TI  - Angiotensin II increases urokinase-type plasminogen activator expression and
      induces aneurysm in the abdominal aorta of apolipoprotein E-deficient mice.
AB  - Urokinase-type plasminogen activator (uPA) is increased in human abdominal aortic
      aneurysm (AAA). Chronic infusion of angiotensin II (Ang II) results in AAA in
      apolipoprotein E-deficient mice. We tested the hypothesis that Ang II infusion
      results in an elevation of uPA expression contributing to aneurysm formation. Ang
      II or vehicle was infused by osmotic pumps into apoE-KO mice. All mice treated
      with Ang II developed a localized expansion of the suprarenal aorta (75% increase
      in outer diameter), accompanied by an elevation of blood pressure (22 mmHg),
      compared to the vehicle-treated group. Histological examination of the dilated
      aortic segment revealed similarities to human AAA including focal elastin
      fragmentation, macrophage infiltration, and intravascular hemorrhage. Ang II
      treatment resulted in a 13-fold increase in the expression of uPA mRNA in the AAA
      segment in contrast to a twofold increase in the atherosclerotic aortic arch.
      Increased uPA protein was detected in the abdominal aorta as early as 10 days
      after Ang II infusion before significant aorta expansion. Thus, Ang II infusion
      results in macrophage infiltration, increased uPA activity, and aneurysm
      formation in the abdominal aorta of apoE-KO mice. These data are consistent with
      a causal role for uPA in the pathogenesis of AAA.

PMID- 11583974
TI  - Dissection of key events in tubular epithelial to myofibroblast transition and
      its implications in renal interstitial fibrosis.
AB  - Myofibroblast activation is a key event playing a critical role in the
      progression of chronic renal disease. Emerging evidence suggests that
      myofibroblasts can derive from tubular epithelial cells by an epithelial to
      mesenchymal transition (EMT); however, the details regarding the conversion
      between these two cell types are poorly understood. Here we dissect the key
      events during the process of EMT induced by transforming growth factor-beta1.
      Incubation of human tubular epithelial cells with transforming growth factor
      beta1 induced de novo expression of alpha-smooth muscle actin, loss of epithelial
      marker E-cadherin, transformation of myofibroblastic morphology, and production
      of interstitial matrix. Time-course studies revealed that loss of E-cadherin was
      an early event that preceded other alterations during EMT. The transformed cells
      secreted a large amount of matrix metalloproteinase-2 that specifically degraded
      tubular basement membrane. They also exhibited an enhanced motility and invasive
      capacity. These alterations in epithelial phenotypes in vitro were essentially
      recapitulated in a mouse model of renal fibrosis induced by unilateral ureteral
      obstruction. Hence, these results indicate that tubular epithelial to
      myofibroblast transition is an orchestrated, highly regulated process involving
      four key steps including: 1) loss of epithelial cell adhesion, 2) de novo alpha
      smooth muscle actin expression and actin reorganization, 3) disruption of tubular
      basement membrane, and 4) enhanced cell migration and invasion.

PMID- 11583975
TI  - Mitochondrial alterations caused by defective peroxisomal biogenesis in a mouse
      model for Zellweger syndrome (PEX5 knockout mouse).
AB  - Zellweger syndrome (cerebro-hepato-renal syndrome) is the most severe form of the
      peroxisomal biogenesis disorders leading to early death of the affected children.
      To study the pathogenetic mechanisms causing organ dysfunctions in Zellweger
      syndrome, we have recently developed a knockout-mouse model by disrupting the
      PEX5 gene, encoding the targeting receptor for most peroxisomal matrix proteins
      (M Baes, P Gressens, E Baumgart, P Carmeliet, M Casteels, M Fransen, P Evrard, D
      Fahimi, PE Declercq, D Collen, PP van Veldhoven, GP Mannaerts: A mouse model for
      Zellweger syndrome. Nat Genet 1997, 17:49-57). In this study, we present evidence
      that the absence of functional peroxisomes, causing a general defect in
      peroxisomal metabolism, leads to proliferation of pleomorphic mitochondria with
      severe alterations of the mitochondrial ultrastructure, changes in the expression
      and activities of mitochondrial respiratory chain complexes, and an increase in
      the heterogeneity of the mitochondrial compartment in various organs and specific
      cell types (eg, liver, proximal tubules of the kidney, adrenal cortex, heart,
      skeletal and smooth muscle cells, neutrophils). The changes of mitochondrial
      respiratory chain enzymes are accompanied by a marked increase of mitochondrial
      manganese-superoxide dismutase, as revealed by in situ hybridization and
      immunocytochemistry, suggesting increased production of reactive oxygen species
      in altered mitochondria. This increased oxidative stress induced probably by
      defective peroxisomal antioxidant mechanisms combined with accumulation of lipid
      intermediates of peroxisomal beta-oxidation system could contribute significantly
      to the pathogenesis of multiple organ dysfunctions in Zellweger syndrome.

PMID- 11583976
TI  - Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene
      expression in natural killer cell lymphoma and various types of
      lymphomas/leukemias : combination analysis with cDNA expression array and tissue
      microarray.
AB  - To investigate the lymphomagenesis of NK/T lymphoma, we comprehensively and
      systematically analyzed the expression pattern of the human NK/T cell line (NK
      YS) genome by cDNA expression array and tissue microarray. We detected
      significant changes in the gene expression of NK-YS cell line: an increase in 18
      and a decrease in 20 genes compared to normal NK cells or peripheral blood
      mononuclear cells. Among these genes, we found a strong decrease in hematopoietic
      cell specific protein-tyrosine-phosphatase SH-PTP1 (SHP1) mRNA by cDNA expression
      array and reverse transcriptase-polymerase chain reaction. Further analysis with
      standard immunohistochemistry and tissue microarray, which used 207 paraffin
      embedded specimens of various kinds of malignant lymphomas, showed that 100% of
      NK/T lymphoma specimens and more than 95% of various types of malignant lymphoma
      were negative for SHP1 protein expression. On the other hand, SHP1 protein was
      strongly expressed in the mantle zone and interfollicular zone lymphocytes in
      reactive lymphoid hyperplasia specimens. In addition, various kinds of
      hematopoietic cell lines, particularly the highly aggressive lymphoma/leukemia
      lines, lacked SHP1 expression in vitro, suggesting that loss of SHP1 expression
      may be related to not only malignant transformation, but also tumor cell
      aggressiveness. SHP1 expression could not be induced in either of two NK/T cell
      lines by phorbol ester, suggesting that genetic impairment or modification with
      methylation of SHP1 DNA could be one of the critical events in the pathogenesis
      of NK/T lymphoma. This evidence strongly suggests that loss of SHP1 gene
      expression plays an important role in multistep tumorigenesis, possibly as an
      anti-oncogene in the wide range of lymphomas/leukemias as well as NK/T lymphomas.

PMID- 11583977
TI  - Mitochondrial toxin 3-nitropropionic acid induces cardiac and neurotoxicity
      differentially in mice.
AB  - We investigated the effects of 3-nitropropionic acid (3NPA), a previously
      characterized neurotoxin, in four strains of mice to better understand the
      molecular basis of variable host responses to this agent. Unexpectedly, we found
      significant cardiac toxicity that always accompanied the neurotoxicity in all
      strains of mice in acute and subacute/chronic toxicity testing. Caudate putamen
      infarction never occurred without cardiac toxicity. All mouse strains tested are
      sensitive to 3NPA although the C57BL/6 and BALB/c mice require more exposure than
      129SVEMS and FVB/n mice. Cardiac toxicity alone was found in 50% of symptomatic
      mice tested and morphologically, the cardiac toxicity is characterized by diffuse
      swelling of cardiomyocytes and multifocal coagulative contraction band necrosis.
      In subacute to chronic exposure, atrial thrombosis, cardiac mineralization, cell
      loss, and fibrosis are combined with cardiomyocyte swelling and necrosis.
      Ultrastructurally, mitochondrial swelling occurs initially, followed by
      disruption of myofilaments. Biochemically, isolated heart mitochondria from the
      highly sensitive 129SVEMS mice have a significant reduction of succinate
      dehydrogenase activity, succinate oxygen consumption rates, and heart adenosine
      triphosphate after 3NPA treatment. The severity of morphological changes
      parallels the biochemical alterations caused by 3NPA, consistent with cardiac
      toxicity being a consequence of the effects of 3NPA on succinate dehydrogenase.
      These experiments show, for the first time, that 3NPA has important cardiotoxic
      effects as well as neurotoxic effects, and that cardiac toxicity possibly
      resulting from inhibition of the succinate dehydrogenase in heart mitochondria,
      contributes to the cause of death in 3NPA poisoning in acute and subacute/chronic
      studies in mice.

PMID- 11583978
TI  - Fractalkine: a novel angiogenic chemokine in rheumatoid arthritis.
AB  - Angiogenesis is an important aspect of the vasculoproliferation found in the
      rheumatoid arthritic (RA) pannus. We have previously implicated members of the
      CXC chemokine family as potent angiogenic mediators in RA. We investigated the
      possibility that the sole member of the CX(3)C chemokine family, fractalkine
      (fkn), induces angiogenesis and that fkn might mediate angiogenesis in RA.
      Recombinant human fkn significantly induced migration of human dermal
      microvascular endothelial cells (HMVECs), a facet of the angiogenic response, in
      the pmol/L range in a concentration-dependent manner (P < 0.05). Fkn also induced
      the formation of significantly more endothelial tubes on Matrigel than did a
      negative control (P < 0.05). Fkn significantly induced 2.3-fold more blood vessel
      growth than control in the in vivo Matrigel plug assays (P < 0.05). We identified
      HMVEC expression of the fkn receptor, CX(3)CR1. Next, we determined if RA
      synovial fluid (SF)-induced angiogenesis was fkn-dependent. SFs from six RA
      patients immunodepleted of soluble fkn induced 56% less migration of HMVECs than
      did sham-depleted RA SFs (P < 0.05). In vivo, immunodepletion of fkn from six RA
      SFs significantly inhibited their angiogenic activity in Matrigel plug assays (P
      < 0.05). Immunodepletion of fkn from five RA synovial tissue homogenates
      inhibited their ability to induce angiogenesis in in vivo Matrigel plug assays (P
      < 0.05). These results establish a new function for fkn as an angiogenic mediator
      and suggest that it may mediate angiogenesis in RA.

PMID- 11583979
TI  - Exclusive neutrophil recruitment with oncostatin M in a human system.
AB  - Oncostatin M (OSM), a member of the IL-6 family has been postulated to be a
      potent recruiter of leukocytes, however information regarding the molecular
      mechanism(s) underlying this event is extremely limited. Therefore, the aim of
      this study was to investigate the role of OSM-mediated leukocyte recruitment in a
      human system in vitro under flow conditions. A parallel-plate flow chamber assay
      was used to examine leukocyte recruitment from whole blood by human umbilical
      vein endothelium treated for 24 hours with OSM. OSM in a dose-response manner
      revealed very significant leukocyte rolling and adhesion reaching optimal levels
      at a very low concentration of OSM (10 ng/ml). The OSM-induced leukocyte rolling
      and adhesion was comparable to levels seen with tumor necrosis factor. OSM was
      extremely selective for neutrophil recruitment (96%) with <3% lymphocyte
      recruitment. By contrast, tumor necrosis factor-alpha revealed no such
      selectivity, recruiting 70% neutrophils and at least 25% lymphocytes and
      detectable levels of eosinophils at 24 hours. The molecular mechanism underlying
      the leukocyte recruitment seemed to be entirely dependent on P-selectin as
      leukocyte recruitment could be completely blocked by the addition of a P-selectin
      blocking antibody. An elevation in both P-selectin message and protein was
      observed with 24 hours of OSM stimulation of endothelium. By contrast, E-selectin
      and VCAM-1 were not detectable after OSM stimulation. Similar results were seen
      with passaged dermal microvascular endothelium that does not have a prestored
      pool of P-selectin. Based on these results, we conclude that OSM may be a very
      selective potent recruiter of neutrophils in more prolonged inflammatory
      conditions, an event exclusively dependent on P-selectin.

PMID- 11583980
TI  - Differential cellular expression of neurotrophins in cortical tubers of the
      tuberous sclerosis complex.
AB  - Neurotrophins and their receptors modulate cerebral cortical development. Tubers
      in the tuberous sclerosis complex (TSC) are characterized histologically by
      disorganized cortical cytoarchitecture and thus, we hypothesized that expression
      of neurotrophin mRNAs and proteins might be altered in tubers. Using in situ
      transcription and mRNA amplification to probe cDNA arrays, we found that
      neurotrophin-3 (NT3) and trkB mRNA expression were reduced whereas neurotrophin-4
      (NT4) and trkC mRNA expression were increased in whole tuber sections.
      Alterations in mRNA abundance were defined in single microdissected dysplastic
      neurons (DNs) and giant cells (GCs). NT3 mRNA expression was reduced in GCs and
      trkB mRNA expression was reduced in DNs. NT4 mRNA expression was increased in DNs
      and trkC mRNA expression was increased in both DNs and GCs. In three patients,
      TSC2 locus mutations were confirmed and the mean tuberin mRNA expression levels
      was reduced across all nine cases. Consistent with these observations, NT3 mRNA
      expression was reduced but trkC mRNA expression was increased in vitro in human
      NTera2 neurons (NT2N) transfected with a tuberin antisense construct that reduced
      tuberin expression. Western analysis of tuber homogenates and computer-assisted
      densitometry of immunolabeled sections confirmed the neurotrophin mRNA expression
      data in whole sections and single neurotrophin immunoreactive cells. We conclude
      that alterations in NT4/trkB and NT3/trkC expression may contribute to tuber
      formation during brain development as downstream effects of the hamartin and
      tuberin pathway in TSC.

PMID- 11583981
TI  - Matrix metalloproteinases: a role in the contraction of vitreo-retinal scar
      tissue.
AB  - The most common cause of failure of retinal reattachment surgery is formation of
      fibrocellular contractile membranes on both surfaces of the neuroretina. This
      intraocular fibrosis, known as proliferative vitreoretinopathy, results in a
      blinding tractional retinal detachment because of the contractile nature of the
      membrane. Contractility is a cell-mediated event that is thought to be dependent
      on locomotion and adhesion to the extracellular matrix. Interactions between
      cells and the extracellular matrix can be influenced by matrix metalloproteinases
      (MMPs) and we investigated the role of MMPs in two in vitro models (two- and
      three-dimensional) of human retinal pigment epithelial (RPE) cell-mediated
      contraction. MMP activity was detected using enzyme-linked immunosorbent assays
      and zymography techniques that revealed MMP-1, -2, -3, and -9 positivity during
      the collagen matrix contraction assays. RPE-populated collagen matrix contraction
      (three-dimensional) was inhibited using a cocktail of anti-MMP antibodies and
      with Galardin (a broad-spectrum MMP inhibitor). Galardin inhibition was dose
      dependent, reversible, and dependent on cell number. MMP inhibitors had no effect
      on contraction when RPEs were seeded on two-dimensional collagen matrices or on
      cellular adhesion to collagen type I. Our results suggest that MMP activity may
      be required for three-dimensional but not two-dimensional RPE-collagen matrix
      contraction.

PMID- 11583982
TI  - Tumor progression of skin carcinoma cells in vivo promoted by clonal selection,
      mutagenesis, and autocrine growth regulation by granulocyte colony-stimulating
      factor and granulocyte-macrophage colony-stimulating factor.
AB  - Tumor microenvironment is crucial for cancer growth and progression as evidenced
      by reports on the significance of tumor angiogenesis and stromal cells. Using the
      HaCaT/HaCaT-ras human skin carcinogenesis model, we studied tumor progression
      from benign tumors to highly malignant squamous cell carcinomas. Progression of
      tumorigenic HaCaT-ras clones to more aggressive and eventually metastatic
      phenotypes was reproducibly achieved by their in vivo growth as subcutaneous
      tumors in nude mice. Their enhanced malignant phenotype was stably maintained in
      recultured tumor cells that represented, identified by chromosomal analysis, a
      distinct subpopulation of the parental line. Additional mutagenic effects were
      apparent in genetic alterations involving chromosomes 11 and 2, and in
      amplification and overexpression of the H-ras oncogene. Importantly, in vitro
      clonal selection of benign and malignant cell lines never resulted in late-stage
      malignant clones, indicating the importance of the in vivo environment in
      promoting an enhanced malignant phenotype. Independently of their H-ras status,
      all in vivo-progressed tumor cell lines (five of five) exhibited a constitutive
      and stable expression of the hematopoietic growth factors granulocyte colony
      stimulating factor and granulocyte-macrophage colony-stimulating factor, which
      may function as autocrine/paracrine mediators of tumor progression in vivo. Thus,
      malignant progression favored by the in vivo microenvironment requires both
      clonal selection of subpopulations adapted to in vivo growth and mutational
      events leading to stable functional alterations.

PMID- 11583983
TI  - Lack of cytosolic and transmembrane domains of type XIII collagen results in
      progressive myopathy.
AB  - Type XIII collagen is a type II transmembrane protein found at many sites of cell
      adhesion in tissues. Homologous recombination was used to generate a transgenic
      mouse line (Col13a1(N/N)) that expresses N-terminally altered type XIII collagen
      molecules lacking the short cytosolic and transmembrane domains but retaining the
      large collagenous ectodomain. The mutant molecules were correctly transported to
      focal adhesions in cultured fibroblasts derived from the Col13a1(N/N) mice, but
      the cells showed decreased adhesion when plated on type IV collagen. These mice
      were viable and fertile, and in immunofluorescence stainings the mutant protein
      was located in adhesive tissue structures in the same manner as normal
      alpha1(XIII) chains. In immunoelectron microscopy of wild-type mice type XIII
      collagen was detected at the plasma membrane of skeletal muscle cells whereas in
      the mutant mice the protein was located in the adjacent extracellular matrix.
      Affected skeletal muscles showed abnormal myofibers with a fuzzy plasma membrane
      basement membrane interphase along the muscle fiber and at the myotendinous
      junctions, disorganized myofilaments, and streaming of z-disks. The findings were
      progressive and the phenotype was aggravated by exercise. Thus type XIII collagen
      seems to participate in the linkage between muscle fiber and basement membrane, a
      function impaired by lack of the cytosolic and transmembrane domains.

PMID- 11583984
TI  - Is hepatitis C virus a sialotropic virus?

PMID- 11583985
TI  - Characterization of a presenilin-mediated amyloid precursor protein carboxyl
      terminal fragment gamma. Evidence for distinct mechanisms involved in gamma 
      secretase processing of the APP and Notch1 transmembrane domains.
AB  - A variety of investigations have led to the conclusion that presenilins (PS) play
      a critical role in intramembranous, gamma-secretase proteolysis of selected type
      I membrane proteins, including Notch1 and amyloid precursor protein (APP). We now
      show that the generation of the S3/Notch intracellular domain and APP-carboxyl
      terminal fragment gamma (CTFgamma) derivatives are dependent on PS expression and
      inhibited by a highly selective and potent gamma-secretase inhibitor.
      Unexpectedly, the APP-CTFgamma derivative is generated by processing between Leu
      645 and Val-646 (of APP(695)), several amino acids carboxyl-terminal to the
      scissile bonds for production of amyloid beta protein peptides. Although the
      relationship of APP-CTFgamma to the production of amyloid beta protein peptides
      is not known, we conclude that in contrast to the highly selective PS-dependent
      processing of Notch, the PS-dependent gamma-secretase processing of APP is
      largely nonselective and occurs at multiple sites within the APP transmembrane
      domain.

PMID- 11583986
TI  - Collapsin response mediator protein switches RhoA and Rac1 morphology in N1E-115
      neuroblastoma cells and is regulated by Rho kinase.
AB  - The formation and directional guidance of neurites involves dynamic regulation of
      Rho family GTPases. Rac and Cdc42 promote neurite outgrowth, whereas Rho
      activation causes neurite retraction. Here we describe a role for collapsin
      response mediator protein (Crmp-2), a neuronal protein implicated in axonal
      outgrowth and a component of the semaphorin 3A pathway, in switching GTPase
      signaling when expressed in combination with either dominant active Rac or Rho.
      In neuroblastoma N1E-115 cells, co-expression of Crmp-2 with dominant active RhoA
      V14 induced Rac morphology, cell spreading and ruffling (and the formation of
      neurites). Conversely, co-expression of Crmp-2 with dominant active Rac1 V12
      inhibited Rac morphology, and in cells already expressing Rac1 V12, Crmp-2 caused
      localized peripheral collapse, involving Rho (and Cdc42) activation. Rho kinase
      was a pivotal regulator of Crmp-2; Crmp-2 phosphorylation was required for Crmp
      2/Rac1 V12 inhibition, but not Crmp-2/RhoA V14 induction, of Rac morphology. Thus
      Crmp-2, regulated by Rho kinase, promotes outgrowth and collapse in response to
      active Rho and Rac, respectively, reversing their usual morphological effects and
      providing a mechanism for dynamic modulation of growth cone guidance.

PMID- 11583987
TI  - PML-RARalpha alleviates the transcriptional repression mediated by tumor
      suppressor Rb.
AB  - A fusion between the promyelocytic leukemia (PML) protein and the retinoic acid
      receptor-alpha (RARalpha) results in the transforming protein of acute
      promyelocytic leukemia, PML-RARalpha. PML has growth-suppressive properties and
      is localized within distinct nuclear structures referred to as nuclear bodies.
      PML participates in numerous cellular functions, including transcriptional
      activation, apoptosis, and transcriptional repression, whereas PML-RARalpha
      blocks these functions. However, the role played by PML-RARalpha in
      leukemogenesis remains unclear. Here we report that PML is required for
      transcriptional repression mediated by the tumor suppressor Rb. Rb interacts with
      the histone decaetylase (HDAC) complex containing co-repressors and represses the
      transcription of the E2F target genes. Overexpression of PML enhanced Rb-mediated
      repression. The degree of Rb-mediated repression was weakened by injecting anti
      PML antibodies and was lower in Pml-deficient mouse embryonic fibroblasts. PML
      RARalpha inhibited Rb-mediated repression, and two co-repressor-interacting sites
      on the PML-RARalpha molecule were required for this activity. Furthermore, PML
      RARalpha blocked the interaction between Rb and HDAC. Thus, aberrant binding of
      PML-RARalpha to co-repressor-HDAC complexes may inhibit their association with
      Rb, resulting in the abrogation of Rb activity. Thus, the disruption of Rb
      mediated repression may be a contributory factor in leukemogenesis.

PMID- 11583988
TI  - Voltage-independent inhibition of P/Q-type Ca2+ channels in adrenal chromaffin
      cells via a neuronal Ca2+ sensor-1-dependent pathway involves Src family tyrosine
      kinase.
AB  - In common with many neurons, adrenal chromaffin cells possess distinct voltage
      dependent and voltage-independent pathways for Ca(2+) channel regulation. In this
      study, the voltage-independent pathway was revealed by addition of naloxone and
      suramin to remove tonic blockade of Ca(2+) currents via opioid and purinergic
      receptors due to autocrine feedback inhibition. This pathway requires the Ca(2+)
      binding protein neuronal calcium sensor-1 (NCS-1). The voltage-dependent pathway
      was pertussis toxin-sensitive, whereas the voltage-independent pathway was
      largely pertussis toxin-insensitive. Characterization of the voltage-independent
      inhibition of Ca(2+) currents revealed that it did not involve protein kinase C
      dependent signaling pathways but did require the activity of a Src family
      tyrosine kinase. Two structurally distinct Src kinase inhibitors, 4-amino-5-(4
      methylphenyl)7-(t-butyl)pyrazolo[3,4-d] pyrimidine (PP1) and a Src inhibitory
      peptide, increased the Ca(2+) currents, and no further increase in Ca(2+)
      currents was elicited by addition of naloxone and suramin. In addition, the Src
      like kinase appeared to act in the same pathway as NCS-1. In contrast, addition
      of PP1 did not prevent a voltage-dependent facilitation elicited by a strong pre
      pulse depolarization indicating that this pathway was independent of Src kinase
      activity. PPI no longer increased Ca(2+) currents after addition of the P/Q-type
      channel blocker omega-agatoxin TK. The alpha(1A) subunit of P/Q-type Ca(2+)
      channels was immunoprecipitated from chromaffin cell extracts and found to be
      phosphorylated in a PP1-sensitive manner by endogenous kinases in the
      immunoprecipitate. A high molecular mass (around 220 kDa) form of the alpha(1A)
      subunit was detected by anti-phosphotyrosine, suggesting a possible target for
      Src family kinase action. These data demonstrate a voltage-independent mechanism
      for autocrine inhibition of P/Q-type Ca(2+) channel currents in chromaffin cells
      that requires Src family kinase activity and suggests that this may be a widely
      distributed pathway for Ca(2+) channel regulation.

PMID- 11583989
TI  - CTP:phosphocholine cytidylyltransferase alpha is a cytosolic protein in pulmonary
      epithelial cells and tissues.
AB  - CTP:phosphocholine cytidylyltransferase (CCT) is a rate-determining enzyme in de
      novo synthesis of phosphatidylcholine (PC). The lung requires a steady synthesis
      of PC for lung surfactant of which disaturated PC is the essential active agent.
      Surfactant synthesis occurs in alveolar type II cells. Studies with non-pulmonary
      cells have suggested that CCT is both a nuclear and cytoplasmic protein. The
      unusual requirements of the lung for PC synthesis and, therefore, CCT activity
      suggest a unique mechanism of regulation and possibly localization of CCT. The
      localization of CCT alpha in lung epithelial cells and, of greater consequence,
      lung tissues are yet unknown. Three isoforms of CCT have been identified. Herein
      we investigated the localization of the ubiquitously expressed CCT alpha isoform.
      To ascertain CCT alpha localization in lungs and lung-related epithelial cells,
      we employed a number of localization methods. Immunogold electron microscopy
      using polyclonal antibodies raised to either the carboxyl terminus, catalytic
      domain, or amino terminus of CCT alpha localized CCT alpha mostly to the exterior
      plasma membrane or regions of the endoplasmic reticulum (ER) in both A549 and MLE
      15 epithelial lung cell lines and primary cultures of fetal rat lung epithelial
      cells. In contrast to other studies, little or no nuclear labeling was observed.
      Indirect immunofluorescence of these cells with anti-CCT alpha antibodies
      resulted in a similar distribution. Indirect visualization of both hemagglutinin-
      and FLAG-tagged CCT alpha as well as direct visualization of enhanced green
      fluorescence protein-CCT alpha fusion protein corroborated a cytoplasmic
      localization of CCT alpha in pulmonary cells. Moreover, analysis of lung tissue
      from fetal and adult mouse by either immunogold electron microscopy or indirect
      immunofluorescence yielded a strong cytoplasmic CCT alpha signal with virtually
      no nuclear localization in epithelial cells lining the airways. The cytoplasmic
      localization of CCT alpha in type II cells was further substantiated with
      transgenic mice overexpressing FLAG-tagged CCT alpha using the lung-specific
      human surfactant protein C (SP-C) promoter. We conclude that CCT alpha does not
      localize to the nucleus in pulmonary tissues, and, therefore, nuclear
      localization of CCT alpha is not a universal event.

PMID- 11583990
TI  - Inhibition of the Escherichia coli pyruvate dehydrogenase complex E1 subunit and
      its tyrosine 177 variants by thiamin 2-thiazolone and thiamin 2-thiothiazolone
      diphosphates. Evidence for reversible tight-binding inhibition.
AB  - Variants of the pyruvate dehydrogenase subunit (E1; EC ) of the Escherichia coli
      pyruvate dehydrogenase multienzyme complex with Y177A and Y177F substitutions
      were created. Both variants displayed pyruvate dehydrogenase multienzyme complex
      activity at levels of 11% (Y177A E1) and 7% (Y177F E1) of the parental enzyme.
      The K(m) values for thiamin diphosphate (ThDP) were 1.58 microm (parental E1) and
      6.65 microm (Y177A E1), whereas the Y177F E1 variant was not saturated at 200
      microm. According to fluorescence studies, binding of ThDP was unaffected by the
      Tyr(177) substitutions. The ThDP analogs thiamin 2-thiazolone diphosphate (ThTDP)
      and thiamin 2-thiothiazolone diphosphate (ThTTDP) behaved as tight-binding
      inhibitors of parental E1 (K(i) = 0.003 microm for ThTDP and K(i) = 0.064 microm
      for ThTTDP) and the Y177A and Y177F variants. This analysis revealed that ThTDP
      and ThTTDP bound to parental E1 via a two-step mechanism, but that ThTDP bound to
      the Y177A variant via a one-step mechanism. Binding of ThTDP was affected and
      that of ThTTDP was unaffected by substitutions at Tyr(177). Addition of ThDP or
      ThTDP to parental E1 resulted in similar CD spectral changes in the near-UV
      region. In contrast, binding of ThTTDP to either parental E1 or the Y177A and
      Y177F variants was accompanied by the appearance of a positive band at 330 nm,
      indicating that ThTTDP was bound in a chiral environment. In combination with x
      ray structural evidence on the location of Tyr(177), the kinetic and
      spectroscopic data suggest that Tyr(177) has a role in stabilization of some
      transition state(s) in the reaction pathway, starting with the free enzyme and
      culminating with the first irreversible step (decarboxylation), as well as in
      reductive acetylation of the dihydrolipoamide acetyltransferase component.

PMID- 11583991
TI  - Cellular energetics in the preconditioned state: protective role for
      phosphotransfer reactions captured by 18O-assisted 31P NMR.
AB  - Cell survival is critically dependent on the preservation of cellular
      bioenergetics. However, the metabolic mechanisms that confer resistance to injury
      are poorly understood. Phosphotransfer reactions integrate ATP-consuming with ATP
      producing processes and could thereby contribute to the generation of a
      protective phenotype. Here, we used ischemic preconditioning to induce a stress
      tolerant state and (18)O-assisted (31)P nuclear magnetic resonance spectroscopy
      to capture intracellular phosphotransfer dynamics. Preconditioning of isolated
      perfused hearts triggered a redistribution in phosphotransfer flux with
      significant increase in creatine kinase and glycolytic rates. High energy
      phosphoryl fluxes through creatine kinase, adenylate kinase, and glycolysis in
      preconditioned hearts correlated tightly with post-ischemic functional recovery.
      This was associated with enhanced metabolite exchange between subcellular
      compartments, manifested by augmented transfer of inorganic phosphate from
      cellular ATPases to mitochondrial ATP synthase. Preconditioning-induced energetic
      remodeling protected cellular ATP synthesis and ATP consumption, improving
      contractile performance following ischemia-reperfusion insult. Thus, the
      plasticity of phosphotransfer networks contributes to the effective functioning
      of the cellular energetic system, providing a mechanism for increased tolerance
      toward injury.

PMID- 11583992
TI  - Putative ACP phosphodiesterase gene (acpD) encodes an azoreductase.
AB  - An FMN-dependent NADH-azoreductase of Escherichia coli was purified and analyzed
      for identification of the gene responsible for azo reduction by microorganisms.
      The N-terminal sequence of the azoreductase conformed to that of the acpD gene
      product, acyl carrier protein phosphodiesterase. Overexpression of the acpD gene
      provided the E. coli with a large amount of the 23-kDa protein and more than 800
      times higher azoreductase activity. The purified gene product exhibited activity
      corresponding to that of the native azoreductase. The reaction followed a ping
      pong mechanism requiring 2 mol of NADH to reduce 1 mol of methyl red (4'
      dimethylaminoazobenzene-2-carboxylic acid) into 2-aminobenzoic acid and N,N'
      dimethyl-p-phenylenediamine. On the other hand, the gene product could not
      convert holo-acyl carrier protein into the apo form under either in vitro or in
      vivo conditions. These data indicate that the acpD gene product is not acyl
      carrier protein phosphodiesterase but an azoreductase.

PMID- 11583993
TI  - Transcriptional regulation of mouse delta-opioid receptor gene: role of Ets-1 in
      the transcriptional activation of mouse delta-opioid receptor gene.
AB  - Previously, we identified a minimum core promoter of the mouse delta-opioid
      receptor (DOR) gene. The DOR promoter contains an E-box that binds upstream
      stimulatory factor and is crucial for the DOR promoter activity in NS20Y cells, a
      mouse neuronal cell line that constitutively expresses DOR. In the present study,
      we further analyzed the DOR promoter in NS20Y cells and have demonstrated that
      transcription factor Ets-1 binds to an Ets-1-binding site overlapping the E-box
      and trans-activates the DOR promoter by synergizing with upstream stimulatory
      factor in specific DNA binding. In addition, the Ets-1 DNA-binding domain is
      sufficient to play the functional role of Ets-1 in trans-activating the DOR
      promoter. Furthermore, through in vivo cross-linking assays and Northern blot
      analyses, we have demonstrated that Ets-1 binds to the DOR promoter in the
      neonatal mouse brain and that overexpressed Ets-1 can significantly enhance the
      expression of DOR mRNA in primary neonatal mouse neuronal cells. Collectively,
      our data suggest that Ets-1 functions as a trans-activator of the DOR promoter in
      the neonatal mouse brain and thus may contribute to the development of the mouse
      brain DOR system.

PMID- 11583994
TI  - Population analysis of subsaturated 172-12 nucleosomal arrays by atomic force
      microscopy detects nonrandom behavior that is favored by histone acetylation and
      short repeat length.
AB  - Concatameric 5 S rDNA templates reconstituted in vitro into nucleosomal arrays
      provide very popular chromatin models for many kinds of studies. Here, atomic
      force microscopy is used to determine the population distributions for one such
      nucleosomal array, the 172-12, reconstituted to various subsaturated levels with
      nonacetylated or hyperacetylated HeLa histones. This array is a model for short
      linker length genomes and transcriptionally active and newly replicated
      chromatins. The analysis shows that as input histone levels increase, template
      occupation increases progressively as discrete population distributions. The
      distributions are random at low (n(av) < 4) and high (n(av) > 8) loadings but
      display specific nonrandom features, such as a deficit of molecules with one
      nucleosome more or less than the peak species in the distribution and enhanced
      distribution breadths, in the mid-range (n(av) = 4-8). Thus, the mid-range of
      occupation on polynucleosomal arrays may be a special range for chromatin
      structure and/or assembly. The mid-range nonrandom features are enhanced in
      distributions from short repeat (172-12) arrays, particularly for unacetylated
      chromatin, and in distributions from hyperacetylated chromatin, particularly for
      long repeat (208-12) arrays. Thus, short repeat length and acetylation can affect
      basic chromatin properties, like population tendencies, in very similar ways and
      therefore may cause similar changes in chromatin structure. Some possible effects
      are suggested. The data also indicate that it is thermodynamically more difficult
      for hyperacetylated nucleosomes to assemble onto the 172-12 templates, a result
      having implications for in vivo chromatin assembly.

PMID- 11583996
TI  - Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in
      the absence of caspase-8.
AB  - Caspase-8 is believed to play an obligatory role in apoptosis initiation by death
      receptors, but the role of its structural relative, caspase-10, remains
      controversial. Although earlier evidence implicated caspase-10 in apoptosis
      signaling by CD95L and Apo2L/TRAIL, recent studies indicated that these death
      receptor ligands recruit caspase-8 but not caspase-10 to their death-inducing
      signaling complex (DISC) even in presence of abundant caspase-10. We
      characterized a series of caspase-10-specific antibodies and found that certain
      commercially available antibodies cross-react with HSP60, shedding new light on
      previous results. The majority of 55 lung and breast carcinoma cell lines
      expressed mRNA for both caspase-8 and -10; however, immunoblot analysis revealed
      that caspase-10 protein expression was more frequently absent than that of
      caspase-8, suggesting a possible selective pressure against caspase-10 production
      in cancer cells. In nontransfected cells expressing both caspases, CD95L and
      Apo2L/TRAIL recruited endogenous caspase-10 as well as caspase-8 to their DISC,
      where both enzymes were proteolytically processed with similar kinetics. Caspase
      10 recruitment required the adaptor FADD/Mort1, and caspase-10 cleavage in vitro
      required DISC assembly, consistent with the processing of an apoptosis initiator.
      Cells expressing only one of the caspases underwent ligand-induced apoptosis,
      indicating that each caspase can initiate apoptosis independently of the other.
      Thus, apoptosis signaling by death receptors involves not only caspase-8 but also
      caspase-10, and both caspases may have equally important roles in apoptosis
      initiation.

PMID- 11583995
TI  - Dynamin isoform-specific interaction with the shank/ProSAP scaffolding proteins
      of the postsynaptic density and actin cytoskeleton.
AB  - Dynamin is a GTPase involved in endocytosis and other aspects of membrane
      trafficking. A critical function in the presynaptic compartment attributed to the
      brain-specific dynamin isoform, dynamin-1, is in synaptic vesicle recycling. We
      report that dynamin-2 specifically interacts with members of the Shank/ProSAP
      family of postsynaptic density scaffolding proteins and present evidence that
      dynamin-2 is specifically associated with the postsynaptic density. These data
      are consistent with a role for this otherwise broadly distributed form of dynamin
      in glutamate receptor down-regulation and other aspects of postsynaptic membrane
      turnover.

PMID- 11583997
TI  - Identification of the high affinity binding site in transforming growth factor
      beta involved in complex formation with alpha 2-macroglobulin. Implications
      regarding the molecular mechanisms of complex formation between alpha 2
      macroglobulin and growth factors, cytokines, and hormones.
AB  - The biological activities of transforming growth factor-beta isoforms (TGF
      beta(1,2)) are known to be modulated by alpha(2)-macroglobulin (alpha(2)M).
      alpha(2)M forms complexes with numerous growth factors, cytokines, and hormones,
      including TGF-beta. Identification of the binding sites in TGF-beta isoforms
      responsible for high affinity interaction with alpha(2)M many unravel the
      molecular basis of the complex formation. Here we demonstrate that among nine
      synthetic pentacosapeptides with overlapping amino acid sequences spanning the
      entire TGF-beta(1) molecule, the peptide (residues 41-65) containing Trp-52
      exhibited the most potent activity in inhibiting the formation of complexes
      between (125)I-TGF-beta(1) and activated alpha(2)M (alpha(2)M*) as determined by
      nondenaturing polyacrylamide gel electrophoresis and by plasma clearance in mice.
      TGF-beta(2) peptide containing the homologous sequence and Trp-52 was as active
      as the TGF-beta(1) peptide, whereas the corresponding TGF-beta(3) peptide lacking
      Trp-52, was inactive. The replacement of the Trp-52 with alanine abolished the
      inhibitory activities of these peptides. (125)I-TGF-beta(3), which lacks Trp-52,
      bound to alpha(2)M* with an affinity lower than that of (125)I-TGF-beta(1).
      Furthermore, unlabeled TGF-beta(3) and the mutant TGF-beta(1)W52A, in which Trp
      52 was replaced with alanine, were less potent than unlabeled TGF-beta(1) in
      blocking I(125)-TGF-beta(1) binding to alpha(2)M*. TGF-beta(1) and TGF-beta(2)
      peptides containing Trp-52 were also effective in inhibiting I(125)-nerve growth
      factor binding to alpha(2)M*. Tauhese results suggest that Trp-52 is involved in
      high affinity binding of TGF-beta to alpha(2)M*. They also imply that TGF-beta
      and other growth factors/cytokines/hormones may form complexes with alpha(2)M*
      via a common mechanism involving the interactions between topologically exposed
      Trp and/or other hydrophobic residues and a hydrophobic region in alpha(2)M*.

PMID- 11583998
TI  - Evidence for a mechanism of repression of heat shock factor 1 transcriptional
      activity by a multichaperone complex.
AB  - In the absence of stress, human heat shock factor 1 (hHSF1) is in its unactivated
      form. hHSF1 polypeptide is in a dynamic heterocomplex with Hsp90 and is incapable
      of specifically binding DNA. When cells are stressed, heterocomplex assembly is
      disrupted. Unbound hHSF1 homotrimerizes, acquires DNA binding activity, and
      concentrates in the nucleus, but remains transcriptionally inactive. A subsequent
      reaction converts this inactive, trimeric form into the active,
      hyperphosphorylated transcription factor. Subsequent to the stressful event,
      hHSF1 is deactivated and eventually returned to its unactivated form. Evidence is
      presented herein that trimeric hHSF1 has the propensity to dynamically associate
      with an Hsp90-immunophilin-p23 complex through its regulatory domain. Formation
      of this heterocomplex results in repression of the transcriptional activity of
      trimeric hHSF1. Stress-denatured proteins effectively compete with trimeric hHSF1
      for Hsp90-immunophilin-p23 complex, counteracting assembly of the heterocomplex
      and repression of hHSF1 transcriptional activity. This repression mechanism may
      be required for a proportional transcriptional response to stress. Formation of
      the heterocomplex may also represent the first step toward returning the hHSF1 to
      its unactivated form.

PMID- 11583999
TI  - Molecular shape of the cationic lipid controls the structure of cationic
      lipid/dioleylphosphatidylethanolamine-DNA complexes and the efficiency of gene
      delivery.
AB  - Pyridinium amphiphiles, abbreviated as SAINT, are highly efficient vectors for
      delivery of DNA into cells. Within a group of structurally related compounds that
      differ in transfection capacity, we have investigated the role of the shape and
      structure of the pyridinium molecule on the stability of bilayers formed from a
      given SAINT and dioleoylphosphatidylethanolamine (DOPE) and on the polymorphism
      of SAINT/DOPE-DNA complexes. Using electron microscopy and small angle x-ray
      scattering, a relationship was established between the structure, stability, and
      morphology of the lipoplexes and their transfection efficiency. The structure
      with the lowest ratio of the cross-sectional area occupied by polar over
      hydrophobic domains (SAINT-2) formed the most unstable bilayers when mixed with
      DOPE and tended to convert into the hexagonal structure. In SAINT-2-containing
      lipoplexes, a hexagonal topology was apparent, provided that DOPE was present and
      complex assembly occurred in 150 mm NaCl. If not, a lamellar phase was obtained,
      as for lipoplexes prepared from geometrically more balanced SAINT structures. The
      hexagonal topology strongly promotes transfection efficiency, whereas a strongly
      reduced activity is seen for complexes displaying the lamellar topology. We
      conclude that in the DOPE-containing complexes the molecular shape and the
      nonbilayer preferences of the cationic lipid control the topology of the lipoplex
      and thereby the transfection efficiency.

PMID- 11584000
TI  - Purification and characterization of a Bacillus subtilis 168 nuclease, YokF,
      involved in chromosomal DNA degradation and cell death caused by thermal shock
      treatments.
AB  - We purified and characterized a 39-kDa Bacillus subtilis 168 nuclease that has
      been suggested in this laboratory to be involved in chromosomal DNA degradation
      induced by lethal heat and cold shock treatments in vivo. The nuclease activity
      was inhibited in vitro by aurintricalboxylic acid but not by Zn(2+). By the
      mutant analysis, we identified the 39-kDa nuclease as a product of yokF gene. The
      yokF gene contained a putative lipoprotein signal peptide motif. After in vivo
      exposure to lethal heat and cold stresses, the chromosomal DNA fragmentation was
      reduced in the yokF mutant, which demonstrated about a 2-10-fold higher survival
      rate than the wild type. The yokF mutant was found to be more sensitive to
      mitomycin C than the wild type. The transformation efficiency of the yokF mutant
      was about 10 times higher than that of the wild type. It is suggested that when
      B. subtilis cells are exposed to a stressful thermal shock resulting in membrane
      perturbation, YokF nuclease consequently dislocates into the cytoplasm and then
      attacks DNA.

PMID- 11584001
TI  - The archaeal DNA primase: biochemical characterization of the p41-p46 complex
      from Pyrococcus furiosus.
AB  - We characterized the primase complex of the hyperthermophilic archaeon,
      Pyrococcus furiosus. The two proteins, Pfup41 and Pfup46, have similar sequences
      to the p48 and p58 subunits, respectively, of the eukaryotic DNA polymerase alpha
      primase complex. Unlike previously reported primases, the Pfup41 preferentially
      utilizes deoxyribonucleotides for its de novo synthesis, and moreover, it
      synthesizes up to several kilobases in length in a template-dependent manner
      (Bocquier, A., Liu, L., Cann, I., Komori, K., Kohda, D., and Ishino, Y. (2001)
      Curr. Biol. 11, 452-456). The p41-p46 complex showed higher DNA binding activity
      than the catalytic p41 subunit alone. In addition, the amount of DNA synthesized
      by the p41-p46 complex was much more abundant and shorter in length than that by
      Pfup41 alone. The activity for RNA primer synthesis, which was not detected with
      Pfup41, was observed from the reaction using the p41-p46 complex in vitro. The in
      vitro replication of M13 single-stranded DNA by the P. furiosus proteins was
      stimulated by ATP. Observation of the labeled primers by using [gamma-(32)P]ATP
      in the substrates suggests ATP as the preferable initiating nucleotide for the
      p41-p46 complex. These results show that the primer synthesis activity of Pfup41
      is regulated by Pfup46, and the p41-p46 complex may function as the primase in
      the DNA replication machinery of P. furiosus, in a similar fashion to the
      eukaryotic polymerase alpha-primase complex.

PMID- 11584002
TI  - Acquisition of a specific and potent PTP1B inhibitor from a novel combinatorial
      library and screening procedure.
AB  - Protein-tyrosine phosphatases (PTPases) form a large family of enzymes that serve
      as key regulatory components in signal transduction pathways. Defective or
      inappropriate regulation of PTPase activity leads to aberrant tyrosine
      phosphorylation, which contributes to the development of many human diseases
      including cancers and diabetes. For example, recent gene knockout studies in mice
      identify PTP1B as a promising target for anti-diabetes/obesity drug discovery.
      Thus, there is intense interest in obtaining specific and potent PTPase
      inhibitors for biological studies and pharmacological development. However, given
      the highly conserved nature of the PTPase active site, it is unclear whether
      selectivity in PTPase inhibition can be achieved. We describe a combinatorial
      approach that is designed to target both the active site and a unique peripheral
      site in PTP1B. Compounds that can simultaneously associate with both sites are
      expected to exhibit enhanced affinity and specificity. We also describe a novel
      affinity-based high-throughput assay procedure that can be used for PTPase
      inhibitor screening. The combinatorial library/high-throughput screen protocols
      furnished a small molecule PTP1B inhibitor that is both potent (K(i) = 2.4 nm)
      and selective (little or no activity against a panel of phosphatases including
      Yersinia PTPase, SHP1, SHP2, LAR, HePTP, PTPalpha, CD45, VHR, MKP3, Cdc25A, Stp1,
      and PP2C). These results demonstrate that it is possible to acquire potent, yet
      highly selective inhibitors for individual members of the large PTPase family of
      enzymes.

PMID- 11584003
TI  - The C terminus of the metabotropic glutamate receptor subtypes 2 and 7 specifies
      the receptor signaling pathways.
AB  - There is accumulating evidence that the specificity of the transduction cascades
      activated by G protein-coupled receptors cannot solely depend on the nature of
      the coupled G protein. To identify additional structural determinants, we studied
      two metabotropic glutamate (mGlu) receptors, the mGlu2 and mGlu7 receptors, that
      are both coupled to G(o) proteins but are known to affect different effectors in
      neurons. Thus, the mGlu2 receptor selectively blocks N- and L-type Ca(2+)
      channels via a protein kinase C-independent pathway, whereas the mGlu7 receptor
      selectively blocks P/Q-type Ca(2+) channels via a protein kinase C-dependent
      pathway, and both effects are pertussis toxin-sensitive. We examined the role of
      the C-terminal domain of these receptors in this coupling. Chimeras were
      constructed by exchanging the C terminus of these receptors and transfected into
      neurons. Different chimeric receptors bearing the C terminus of mGlu7 receptor
      blocked selectively P/Q-type Ca(2+) channels, whereas chimeras bearing the C
      terminus of mGlu2 receptor selectively blocked N- and L-type Ca(2+) channels.
      These results show that the C terminus of mGlu2 and mGlu7 receptors is a key
      structural determinant that allows these receptors to select a specific signaling
      pathway in neurons.

PMID- 11584004
TI  - DNA-induced alpha-helical structure in the NH2-terminal domain of histone H1.
AB  - It is important to establish the structural properties of linker histones to
      understand the role they play in chromatin higher order structure and gene
      regulation. Here, we use CD, NMR, and IR spectroscopy to study the conformation
      of the amino-terminal domain of histone H1 degrees, free in solution and bound to
      the DNA. The NH(2)-terminal domain has little structure in aqueous solution, but
      it acquires a substantial amount of alpha-helical structure in the presence of
      trifluoroethanol (TFE). As in other H1 subtypes, the basic residues of the NH(2)
      terminal domain of histone H1 degrees are clustered in its COOH-terminal half.
      According to the NMR results, the helical region comprises the basic cluster
      (Lys(11)-Lys(20)) and extends until Asp(23). The fractional helicity of this
      region in 90% TFE is about 50%. His(24) together with Pro(25) constitute the
      joint between the NH(2)-terminal helix and helix I of the globular domain.
      Infrared spectroscopy shows that interaction with the DNA induces an amount of
      alpha-helical structure equivalent to that observed in TFE. As coulombic
      interactions are involved in complex formation, it is highly likely in the
      complexes with DNA that the minimal region with alpha-helical structure is that
      containing the basic cluster. In chromatin, the high positive charge density of
      the inducible NH(2)-terminal helical element may contribute to the binding
      stability of the globular domain.

PMID- 11584005
TI  - Topology of a human equilibrative, nitrobenzylthioinosine (NBMPR)-sensitive
      nucleoside transporter (hENT1) implicated in the cellular uptake of adenosine and
      anti-cancer drugs.
AB  - The human equilibrative nucleoside transporter hENT1, the first identified member
      of the ENT family of integral membrane proteins, is the primary mechanism for the
      cellular uptake of physiologic nucleosides, including adenosine, and many anti
      cancer nucleoside drugs. We have produced recombinant hENT1 in Xenopus oocytes
      and used native and engineered N-glycosylation sites in combination with
      immunological approaches to experimentally define the membrane architecture of
      this prototypic nucleoside transporter. hENT1 (456 amino acid residues) is shown
      to contain 11 transmembrane helical segments with an amino terminus that is
      intracellular and a carboxyl terminus that is extracellular. Transmembrane
      helices are linked by short hydrophilic regions, except for a large glycosylated
      extracellular loop between transmembrane helices 1 and 2 and a large central
      cytoplasmic loop between transmembrane helices 6 and 7. Sequence analyses suggest
      that this membrane topology is common to all mammalian, insect, nematode,
      protozoan, yeast, and plant members of the ENT protein family.

PMID- 11584006
TI  - Development and characterization of a series of soluble tetrameric and monomeric
      streptavidin muteins with differential biotin binding affinities.
AB  - The strong biotin-streptavidin interaction limits the application of streptavidin
      as a reversible affinity matrix for purification of biotinylated biomolecules. To
      address this concern, a series of single, double, and triple streptavidin muteins
      with different affinities to biotin were designed. The strategy involves mutating
      one to three strategically positioned residues (Ser-45, Thr-90, and Asp-128) that
      interact with biotin and other framework structure-maintaining residues of
      streptavidin. The muteins were produced in soluble forms via secretion from
      Bacillus subtilis. The impact of individual residues on the overall structure of
      streptavidin is reflected by the formation of monomeric streptavidin to different
      extents. Of the three targeted residues, Asp-128 has the most dramatic effect
      (Asp-128 > Thr-90 > Ser-45). Conversion of all three targeted residues to alanine
      results in a soluble biotin binding mutein that exists 100% in the monomeric
      state. Both wild-type and mutated (monomeric and tetrameric) streptavidin
      proteins were purified, and their kinetic parameters (on- and off-rates) were
      determined using a BIAcore biosensor with biotin-conjugated bovine serum albumin
      immobilized to the sensor chip. This series of muteins shows a wide spectrum of
      affinity toward biotin (K(d) from 10(-6) to 10(-11) m). Some of them have the
      potential to serve as reversible biotin binding agents.

PMID- 11584007
TI  - Intra- and intermolecular beta-pleated sheet formation in glutamine-repeat
      inserted myoglobin as a model for polyglutamine diseases.
AB  - An aberrant structure of the expanded polyglutamine might be involved in the
      formation of aggregates in CAG repeat diseases. To elucidate structural
      properties of the expanded polyglutamine, we prepared sperm whale myoglobin (Mb)
      mutants, in which 12, 28, 35, and 50 repeats of glutamine were inserted at the
      corner between the C and D helices (Gln(12), Gln(28), Gln(35), and Gln(50),
      respectively). Circular dichroism and IR spectroscopies showed that the expanded
      polyglutamine, which was recognized by the monoclonal antibody 1C2 in Gln(28),
      Gln(35), and Gln(50) Mb forms an antiparallel beta-pleated sheet structure.
      Gln(50) Mb aggregates were found to comprise an intermolecular antiparallel beta
      pleated sheet. Fluorescence together with (1)H NMR spectra revealed partial
      unfolding of the protein surface in Gln(35) and Gln(50) Mb, although the
      structural changes in the protein core were rather small. The present results
      indicate that the fluctuating beta-pleated sheet of the expanded polyglutamine
      exposed on the protein surface facilitates the formation of aggregates through
      intermolecular interactions. The present study has first established and
      characterized structural properties of a molecular model for polyglutamine
      diseases in which various lengths of polyglutamine including a pathologically
      expanded glutamine repeat were inserted into a structurally known protein.

PMID- 11584008
TI  - Localization of three types of the inositol 1,4,5-trisphosphate receptor/Ca(2+)
      channel in the secretory granules and coupling with the Ca(2+) storage proteins
      chromogranins A and B.
AB  - Although the role of secretory granules as the inositol 1,4,5-trisphosphate
      (IP(3))-sensitive intracellular Ca(2+) store and the presence of the IP(3)
      receptor (IP(3)R)/Ca(2+) channel on the secretory granule membrane have been
      established, the identity of the IP(3)R types present in the secretory granules
      is not known. We have therefore investigated the presence of different types of
      IP(3)R in the secretory granules of bovine adrenal medullary chromaffin cells
      using immunogold electron microscopy and found the existence of all three types
      of IP(3)R in the secretory granules. To determine whether these IP(3)Rs interact
      with CGA and CGB, each IP(3)R isoform was co-transfected with CGA or CGB into
      NIH3T3 or COS-7 cells, and the expressed IP(3)R isoform and CGA or CGB were co
      immunoprecipitated. From these studies it was shown that all three types of
      IP(3)R form complexes with CGA and CGB in the cells. To further confirm whether
      the IP(3)R isoforms and CGA and CGB form a complex in the secretory granules the
      potential interaction between all three isoforms of IP(3)R and CGA and CGB was
      tested by co-immunoprecipitation experiments of the mixture of secretory granule
      lysates and the granule membrane proteins. The three isoforms of IP(3)R were
      shown to form complexes with CGA and CGB, indicating the complex formation
      between the three isoforms of IP(3)R and CGA and CGB in the secretory granules.
      Moreover, the pH-dependent Ca(2+) binding property of CGB was also studied using
      purified recombinant CGB, and it was shown that CGB bound 93 mol of Ca(2+)/mol
      with a dissociation constant (K(d)) of 1.5 mm at pH 5.5 but virtually no Ca(2+)
      at pH 7.5. The high capacity, low affinity Ca(2+)-binding property of CGB at pH
      5.5 is comparable with that of CGA and is in line with its role as a Ca(2+)
      storage protein in the secretory granules.

PMID- 11584009
TI  - Instead of binding calcium, one of the EF-hand structures in guanylyl cyclase
      activating protein-2 is required for targeting photoreceptor guanylyl cyclase.
AB  - Guanylyl cyclase activator proteins (GCAPs) are calcium-binding proteins closely
      related to recoverin, neurocalcin, and many other neuronal Ca(2+)-sensor proteins
      of the EF-hand superfamily. GCAP-1 and GCAP-2 interact with the intracellular
      portion of photoreceptor membrane guanylyl cyclase and stimulate its activity by
      promoting tight dimerization of the cyclase subunits. At low free Ca(2+)
      concentrations, the activator form of GCAP-2 associates into a dimer, which
      dissociates when GCAP-2 binds Ca(2+) and becomes inhibitor of the cyclase. GCAP-2
      is known to have three active EF-hands and one additional EF-hand-like structure,
      EF-1, that deviates form the EF-hand consensus sequence. We have found that
      various point mutations within the EF-1 domain can specifically affect the
      ability of GCAP-2 to interact with the target cyclase but do not hamper the
      ability of GCAP-2 to undergo reversible Ca(2+)-sensitive dimerization. Point
      mutations within the EF-1 region can interfere with both the activation of the
      cyclase by the Ca(2+)-free form of GCAP-2 and the inhibition of retGC basal
      activity by the Ca(2+)-loaded GCAP-2. Our results strongly indicate that
      evolutionary conserved and GCAP-specific amino acid residues within the EF-1 can
      create a contact surface for binding GCAP-2 to the cyclase. Apparently, in the
      course of evolution GCAP-2 exchanged the ability of its first EF-hand motif to
      bind Ca(2+) for the ability to interact with the target enzyme.

PMID- 11584010
TI  - CD19 amplification of B lymphocyte Ca2+ responses: a role for Lyn sequestration
      in extinguishing negative regulation.
AB  - B lymphocyte antigen receptor (BCR) signals are regulated by CD19, with BCR
      induced intracellular calcium ([Ca(2+)](i)) responses enhanced by CD19 co
      ligation. In this study, CD19 engagement using a dimeric anti-CD19 antibody
      induced [Ca(2+)](i) mobilization and significantly enhanced BCR-induced
      [Ca(2+)](i) responses without a requirement for CD19/BCR co-ligation. Although
      simultaneous CD19 and BCR engagement significantly enhanced CD19/Lyn complex
      formation and [Ca(2+)](i) responses, downstream tyrosine phosphorylation of CD22
      and multiple other cellular proteins was inhibited, as was SHP1 recruitment to
      phosphorylated CD22. CD19 overexpression also enhanced BCR-induced [Ca(2+)](i)
      responses, but down-regulated tyrosine phosphorylation of CD22 and multiple other
      cellular proteins following BCR ligation. Because CD19 and Lyn expression are
      genetically titrated in B cells, CD19 engagement may augment BCR-induced
      [Ca(2+)](i) responses by sequestering the available pool of functional Lyn away
      from downstream negative regulatory proteins such as CD22. Consistent with this,
      simultaneous CD19 engagement did not further enhance the BCR-induced [Ca(2+)](i)
      responses of Lyn- or CD22-deficient B cells. Thus, CD19 recruitment of Lyn may
      preferentially activate selective signaling pathways downstream of the CD19/Lyn
      complex to the exclusion of other downstream regulatory and effector pathways.
      Other receptors may also utilize a similar strategy to regulate kinase
      availability and downstream intermolecular signaling.

PMID- 11584011
TI  - The cytochrome c fold can be attained from a compact apo state by occupancy of a
      nascent heme binding site.
AB  - NMR techniques and 8-anilino-1-napthalenesulphonate (ANS) binding studies have
      been used to characterize the apo state of a variant of cytochrome c(552) from
      Hydrogenobacter thermophilus. In this variant the two cysteines that form
      covalent thioether linkages to the heme group have been replaced by alanine
      residues (C11A/C14A). CD studies show that the apo state contains approximately
      14% helical secondary structure, and measurements of hydrodynamic radii using
      pulse field gradient NMR methods show that it is compact (R(h), 16.6 A). The apo
      state binds 1 mol of ANS/mol of protein, and a linear reduction in fluorescence
      enhancement is observed on adding aliquots of hemin to a solution of apo
      C11A/C14A cytochrome c(552) with ANS bound. These results suggest that the bound
      ANS is located in the heme binding pocket, which would therefore be at least
      partially formed in the apo state. Consistent with these characteristics, the
      formation of the holo state of the variant cytochrome c(552) from the apo state
      on the addition of heme has been demonstrated using NMR techniques. The
      properties of the apo state of C11A/C14A cytochrome c(552) reported here contrast
      strongly with those of mitochondrial cytochrome c whose apo state resembles a
      random coil under similar conditions.

PMID- 11584012
TI  - Spatially precise DNA bending is an essential activity of the sox2 transcription
      factor.
AB  - Sox proteins, a subclass of high mobility group box proteins, govern cell fate
      decisions by acting both as classical transcription factors and architectural
      components of chromatin. We aimed to demonstrate that the DNA bending activity of
      Sox proteins is essential to regulate gene expression. We focused on mouse Sox2,
      which participates in the transactivation of the Fgf4 (fibroblast growth factor
      4) gene in the inner cell mass of the blastocyst. We generated six substitutions
      in the high mobility group box of Sox2. One mutant showed a reduced DNA bending
      activity on the Fgf4 enhancer (46 degrees instead of 80 degrees), which resulted
      in more powerful transactivation compared with the wild type protein. We then
      selected two single-base mutations in the Fgf4 enhancer that make the DNA less
      bendable by the Sox2 protein. Again, a different DNA bend (0 degrees and 42
      degrees instead of 80 degrees) resulted in a different activation of
      transcription, but in this case reduced bending corresponded to decreased
      transcription. We found that the opposite effect on transcription of similar DNA
      bending angles is due to a 20 degrees difference in the relative orientation of
      the DNA bends, proving that a correct three-dimensional geometry of enhanceosome
      complexes is necessary to promote transcription.

PMID- 11584013
TI  - Modulation of survival motor neuron pre-mRNA splicing by inhibition of
      alternative 3' splice site pairing.
AB  - Spinal muscular atrophy is caused by the loss of functional survival motor neuron
      (SMN1) alleles. A translationally silent nucleotide transition in the duplicated
      copy of the gene (SMN2) leads to exon 7 skipping and expression of a
      nonfunctional gene product. It has been suggested that differential SMN2 splicing
      is caused by the disruption of an exonic splicing enhancer. Here we show that the
      single nucleotide difference reduces the intrinsic strength of the 3' splice site
      of exon 7 2-fold, whereas the strength of the 5' splice site of the exon 7 is not
      affected. Thus, a decrease in splice site strength is magnified in the context of
      competing exons. These data suggest that lower levels of exon 7 definition not
      only reduce intron 6 removal but, more importantly, increase the efficiency of
      the competing exon 7 skipping pathway. Antisense oligonucleotides were tested to
      modulate exon 7 inclusion, which contains the authentic translation stop codon.
      Oligonucleotides directed toward the 3' splice site of exon 8 were shown to alter
      SMN2 splicing in favor of exon 7 inclusion. These results suggest that antisense
      oligonucleotides could be used as a therapeutic strategy to counteract the
      progression of SMA.

PMID- 11584014
TI  - Diacylglycerol (DAG)-lactones, a new class of protein kinase C (PKC) agonists,
      induce apoptosis in LNCaP prostate cancer cells by selective activation of
      PKCalpha.
AB  - Phorbol esters, the archetypical (PKC) activators, induce apoptosis in androgen
      sensitive LNCaP prostate cancer cells. In this study we evaluate the effect of a
      novel class of PKC ligands, the diacylglycerol (DAG)-lactones, as inducers of
      apoptosis in LNCaP cells. These unique ligands were designed using novel
      pharmacophore- and receptor-guided approaches to achieve highly potent DAG
      surrogates. Two of these compounds, HK434 and HK654, induced apoptosis in LNCaP
      cells with much higher potency than oleoyl-acetyl-glycerol or phorbol 12,13
      dibutyrate. Moreover, different PKC isozymes were found to mediate the apoptotic
      effect of phorbol 12-myristate 13-acetate (PMA) and HK654 in LNCaP cells. Using
      PKC inhibitors and dominant negative PKC isoforms, we found that both PKCalpha
      and PKCdelta mediated the apoptotic effect of PMA, whereas only PKCalpha was
      involved in the effect of the DAG-lactone. The PKCalpha selectivity of HK654 in
      LNCaP cells contrasts with similar potencies in vitro for binding and activation
      of PKCalpha and PKCdelta. Consistent with the differences in isoform dependence
      in intact cells, PMA and HK654 show marked differences in their abilities to
      translocate PKC isozymes. Both PMA and HK654 induce a marked redistribution of
      PKCalpha to the plasma membrane. On the other hand, unlike PMA, HK654
      translocates PKCdelta predominantly to the nuclear membrane. Thus, DAG-lactones
      have a unique profile of activation of PKC isozymes for inducing apoptosis in
      LNCaP cells and represent the first example of a selective activator of a
      classical PKC in cellular models. An attractive hypothesis is that selective
      activation of PKC isozymes by pharmacological agents in cells can be achieved by
      differential intracellular targeting of each PKC.

PMID- 11584015
TI  - The angiogenic factor Cyr61 activates a genetic program for wound healing in
      human skin fibroblasts.
AB  - Cyr61 is a heparin-binding, extracellular matrix-associated protein of the CCN
      family, which also includes connective tissue growth factor, Nov, WISP-1, WISP-2,
      and WISP-3. Cyr61 is capable of multiple functions, including induction of
      angiogenesis in vivo. Purified Cyr61 mediates cell adhesion and induces adhesive
      signaling, stimulates cell migration, enhances cell proliferation, and promotes
      cell survival in both fibroblasts and endothelial cells. In this study, we have
      used cDNA array hybridization to identify genes regulated by Cyr61 in primary
      human skin fibroblasts. The Cyr61-regulated genes fall into several groups known
      to participate in processes important for cutaneous wound healing, including: 1)
      angiogenesis and lymphogenesis (VEGF-A and VEGF-C); 2) inflammation (interleukin
      1beta); 3) extracellular matrix remodeling (MMP1, MMP3, TIMP1, uPA, and PAI-1);
      and 4) cell-matrix interactions (Col1alpha1, Col1alpha2, and integrins alpha(3)
      and alpha(5)). Cyr61-mediated gene expression requires heparin binding activity
      of Cyr61, cellular de novo transcription, and protein synthesis and is largely
      dependent on the activation of p42/p44 MAPKs. Cyr61 regulates gene expression not
      only in serum-free medium but also in fibroblasts cultured on various matrix
      proteins or in the presence of 10% serum. These effects of Cyr61 can be sustained
      for at least 5 days, consistent with the time course of wound healing in vivo.
      Interestingly, Cyr61 can interact with transforming growth factor-beta1 to
      regulate expression of specific genes in an antagonistic, additive, or
      synergistic manner. Furthermore, we show that the Cyr61 gene is highly induced in
      dermal fibroblasts of granulation tissue during cutaneous wound repair. Together,
      these results show that Cyr61 is inducibly expressed in granulation tissues after
      wounding and that Cyr61 activates a genetic program for wound repair in skin
      fibroblasts. We propose a model in which Cyr61 integrates its activities on
      endothelial cells, fibroblasts, and macrophages to regulate the processes of
      angiogenesis, inflammation, and matrix remodeling in the context of cutaneous
      wound healing.

PMID- 11584016
TI  - Nestin is a neuroepithelial target gene of thyroid transcription factor-1, a
      homeoprotein required for forebrain organogenesis.
AB  - Thyroid transcription factor-1 (TTF-1, also known as NKX2.1 and T/EBP), a
      transcription factor belonging to the NKX-2 family of homeodomain-containing
      genes, plays an essential role in the organogenesis of the thyroid gland, lung,
      and ventral forebrain. Nestin is an intermediate filament protein strongly
      expressed in multipotential neuroepithelial stem cells and rapidly down-regulated
      during postnatal life. Here we show that stable fibroblastic clones expressing
      TTF-1 acquire a phenotype reminiscent of neuroepithelial cells in culture and up
      regulate the endogenous nestin gene. TTF-1 transactivates in HeLa and NIH3T3
      cells a reporter gene driven by a central nervous system-specific enhancer
      element from the second intron of the rat nestin gene, where it recognizes a DNA
      binding site (NestBS) whose sequence resembles a nuclear hormone/cAMP-responsive
      element very different from canonical TTF-1 binding sites. Nuclear extracts from
      the head of mouse embryos form a retarded complex with NestBS of the same
      mobility of the extracts obtained from TTF1-expressing clones, which is either
      abolished or supershifted in the presence of two different antibodies recognizing
      the TTF-1 protein. Thus, the neuroepithelial marker nestin is a direct central
      nervous system-specific target gene of TTF-1, leading to the hypothesis that it
      might be the effector through which TTF-1 plays its role in the organogenesis of
      the forebrain.

PMID- 11584017
TI  - The effect of IQGAP1 on Xenopus embryonic ectoderm requires Cdc42.
AB  - IQGAP1 contains a number of protein recognition motifs through which it binds to
      targets. Several in vitro studies have documented that IQGAP1 interacts directly
      with calmodulin, actin, E-cadherin, beta-catenin, and the small GTPases Cdc42 and
      Rac. Nevertheless, direct demonstration of in vivo function of mammalian IQGAP1
      is limited. Using a novel assay to evaluate in vivo function of IQGAP1, we
      document here that microinjection of IQGAP1 into early Xenopus embryos generates
      superficial ectoderm lesions at late blastula stages. This activity was retained
      by the mutated variants of IQGAP1 in which the calponin homology domain or the WW
      domain was deleted. By contrast, deletion of the IQ (IQGAP1-DeltaIQ), Ras-GAP
      related (IQGAP1-DeltaGRD), or C-terminal (IQGAP1-DeltaC) domains abrogated the
      effect of IQGAP1 on the embryos. None of the latter mutants bound Cdc42,
      suggesting that the binding of Cdc42 by IQGAP1 is critical for its function.
      Moreover, overexpression of IQGAP1, but not IQGAP1-DeltaGRD, significantly
      increased the amount of active Cdc42 in embryonic cells. Co-injection of wild
      type IQGAP1 with dominant negative Cdc42, but not the dominant negative forms of
      Rac or Rho, blocked the effect of IQGAP1 on embryonic ectoderm. Together these
      data indicate that the activity of IQGAP1 in embryonic ectoderm requires Cdc42
      function.

PMID- 11584018
TI  - Phosphorylation of the CCAAT displacement protein (CDP)/Cux transcription factor
      by cyclin A-Cdk1 modulates its DNA binding activity in G(2).
AB  - Stable DNA binding by the mammalian CCAAT displacement protein (CDP)/Cux
      transcription factor was previously found to be up-regulated at the G(1)/S
      transition as the result of two events, dephosphorylation by the Cdc25A
      phosphatase and proteolytic processing, to generate an amino-truncated isoform of
      110 kDa. In S phase, CDP/Cux was shown to interact with and repress the core
      promoter of the p21(WAF1) gene. Here we demonstrate that DNA binding by p110
      CDP/Cux is down-modulated as cells progress into G(2). Accordingly, cyclin A-Cdk1
      was found to bind to CDP/Cux and modulate its DNA binding activity in vitro and
      in vivo. Interaction with CDP/Cux required the presence of both cyclin A and a
      cyclin-dependent kinase (Cdk)-activating kinase-activated Cdk1 and involved the
      Cut homeodomain and a downstream Cy motif. Phosphorylation of serines 1237 and
      1270 caused inhibition of DNA binding in vitro. In cotransfection studies, cyclin
      A-Cdk1 inhibited CDP/Cux stable DNA binding and prevented repression of the
      p21(WAF1) reporter. In contrast, mutant CDP/Cux proteins in which serines 1237
      and 1270 were replaced with alanines were not affected by cyclin A-Cdk1. In
      summary, our results suggest that the phosphorylation of CDP/Cux by cyclin A-Cdk1
      contributes to down-modulate CDP/Cux activity as cells progress into the G(2)
      phase of the cell cycle.

PMID- 11584019
TI  - Cellular activation of MMP-2 (gelatinase A) by MT2-MMP occurs via a TIMP-2
      independent pathway.
AB  - The role of membrane-type (MT) 2-matrix metalloproteinase (MMP) in the cellular
      activation of MMP-2 and the tissue inhibitor of matrix metalloproteinase (TIMP)
      requirements for this process have not been clearly established. To address these
      issues a TIMP-2-free cell line derived from a Timp2-/- mouse was transfected for
      stable cell surface expression of hMT2-MMP. Untransfected cells did not activate
      endogenous or exogenous TIMP-2-free MMP-2 unless both TIMP-2 and concanavalin A
      (ConA) were added. Transfected cells expressing hMT2-MMP efficiently activated
      both endogenous and exogenous MMP-2 (within 4 h) via the 68-kDa intermediate in
      the absence of TIMP-2 and ConA. In contrast, activation of MMP-2 by Timp2-/-
      cells expressing recombinant hMT1-MMP occurred more slowly (12 h) and required
      the addition of 0.3-27 nm TIMP-2. Addition of TIMP-2 or TIMP-4 did not enhance
      MMP-2 activation by MT2-MMP at any concentration tested; furthermore, activation
      was inhibited by both TIMPs at concentrations >9 nm, consistent with the similar
      association rate constants (k(on)) calculated for the binding of TIMP-4 and TIMP
      2 to MT2-MMP (3.56 x 10(5) m(-1) s(-1) and 6.52 x 10(5) m(-1) s(-1),
      respectively). MT2-MMP-mediated activation involved cell surface association of
      the MMP-2 in a hemopexin carboxyl-terminal domain (C domain)-dependent manner:
      Exogenous MMP-2 hemopexin C domain blocked activation, and cells expressing hMT2
      MMP did not bind or activate a truncated form of MMP-2 lacking the hemopexin C
      domain. These studies demonstrate the existence of an alternative TIMP-2
      independent pathway for MMP-2 activation involving MT2-MMP, which may be
      important in mediating MMP-2 activation in specific tissues or pathologies where
      MT2-MMP is expressed.

PMID- 11584020
TI  - Conformational changes in thrombin when complexed by serpins.
AB  - Thrombin possesses two positively charged surface domains, termed exosites, that
      orient substrates and inhibitors for reaction with the enzyme. Because the
      exosites also allosterically modulate thrombin's activity, we set out to
      determine whether the structure or function of the exosites changes when thrombin
      forms complexes with antithrombin, heparin cofactor II, or alpha(1)-antitrypsin
      (M358R), serpins that utilize both, one, or neither of the exosites,
      respectively. Using a hirudin-derived peptide to probe the integrity of exosite
      1, no binding was detected when thrombin was complexed with heparin cofactor II
      or alpha(1)-antitrypsin (M358R), and the peptide exhibited a 55-fold lower
      affinity for the thrombin-antithrombin complex than for thrombin. Bound peptide
      or HD-1, an exosite 1-binding DNA aptamer, was displaced from thrombin by each of
      the three serpins. Thrombin binding to fibrin also was abrogated when the enzyme
      was complexed with serpins. These data reveal that, regardless of the initial
      mode of interaction, the function of exosite 1 is lost when thrombin is complexed
      by serpins. In contrast, the integrity of exosite 2 is largely retained when
      thrombin is complexed by serpins, because interaction with heparin or an exosite
      2-directed DNA aptamer was only modestly altered. The disorganization of exosite
      1 that occurs when thrombin is complexed by serpins is consistent with results of
      protease sensitivity studies and crystallographic analysis of a homologous enzyme
      serpin complex.

PMID- 11584021
TI  - The human serotonin 5-HT4 receptor regulates secretion of non-amyloidogenic
      precursor protein.
AB  - The serotonin 5-HT(4) receptor has recently gained a lot of attention for its
      functional roles in central processes such as memory and cognition. In this
      study, we show that activation of the human 5-HT(4) (h5-HT(4)) receptor
      stimulates the secretion of the non-amyloidogenic soluble form of the amyloid
      precursor protein (sAPPalpha). 5-HT enhanced the level of secreted sAPPalpha in a
      time- and dose-dependent manner in Chinese hamster ovary cells stably expressing
      the h5-HT(4(e)) receptor isoform. The increase was inhibited by the selective 5
      HT(4) receptor antagonist, GR113808. The 5-HT(4) selective agonists, prucalopride
      and renzapride, also increased secreted sAPPalpha in IMR32 human neuroblastoma
      cells. The stimulatory effect of 5-HT was mimicked by forskolin, a direct
      activator of adenylyl cyclase, and 8-bromo-cAMP, a membrane-permeant cAMP
      analogue. On the contrary, inhibition of protein kinase A (PKA) by H89
      potentiated the 5-HT-induced increase in both secreted and cellular sAPPalpha.
      This phenomenon involves a novel PKA-independent stimulatory process that
      overcomes a PKA-dependent inhibitory one. Finally, activation of the h5-HT(4(e))
      receptor did not modify extracellular amyloid beta-protein in Chinese hamster
      ovary cells transfected with the human APP695. Given the neuroprotective and
      enhancing memory effects of sAPPalpha, our results may open a new avenue for the
      treatment of Alzheimer's disease.

PMID- 11584022
TI  - Structural basis for the recognition of isoleucyl-adenylate and an antibiotic,
      mupirocin, by isoleucyl-tRNA synthetase.
AB  - An analogue of isoleucyl-adenylate (Ile-AMS) potently inhibits the isoleucyl-tRNA
      synthetases (IleRSs) from the three primary kingdoms, whereas the antibiotic
      mupirocin inhibits only the eubacterial and archaeal IleRSs, but not the
      eukaryotic enzymes, and therefore is clinically used against methicillin
      resistant Staphylococcus aureus. We determined the crystal structures of the
      IleRS from the thermophilic eubacterium, Thermus thermophilus, in complexes with
      Ile-AMS and mupirocin at 3.0- and 2.5-A resolutions, respectively. A structural
      comparison of the IleRS.Ile-AMS complex with the adenylate complexes of other
      aminoacyl-tRNA synthetases revealed the common recognition mode of aminoacyl
      adenylate by the class I aminoacyl-tRNA synthetases. The Ile-AMS and mupirocin,
      which have significantly different chemical structures, are recognized by many of
      the same amino acid residues of the IleRS, suggesting that the antibiotic
      inhibits the enzymatic activity by blocking the binding site of the high energy
      intermediate, Ile-AMP. In contrast, the two amino acid residues that
      concomitantly recognize Ile-AMS and mupirocin are different between the
      eubacterial/archaeal IleRSs and the eukaryotic IleRSs. Mutagenic analyses
      revealed that the replacement of the two residues significantly changed the
      sensitivity to mupirocin.

PMID- 11584023
TI  - A DnaJ protein, apobec-1-binding protein-2, modulates apolipoprotein B mRNA
      editing.
AB  - Mammalian homologues of DnaJ proteins, also known as Hsp40 proteins, are co
      chaperonins that complement Hsp70 chaperone function. Using the yeast two-hybrid
      system, we cloned an apolipoprotein (apo) B mRNA editing complementation protein,
      called apobec-1-binding protein-2 (ABBP-2), and found that it is a Class II DnaJ
      homologue. ABBP-2 binds to apobec-1, the mammalian apoB mRNA editase, via its J
      domain and neighboring G/F domain. It is a ubiquitously expressed protein, and,
      by transfection analysis of GFP-ABBP-2, we found that the protein is located in
      both the nucleus and cytosol of transfected cells, with predominance in the
      nucleus. Down-regulation of ABBP-2 expression in cultured cells inhibits
      endogenous apobec-1-mediated apoB mRNA editing. Like other Hsp40 proteins, ABBP-2
      binds to Hsp70 and has ATPase-stimulating activity. Apobec-1-mediated apoB mRNA
      editing activity of in vitro tissue extracts requires the presence of Hsp70/ABBP
      2. Although exogenously added ATP is not required for editing activity, removal
      of the endogenous ATP present in these extracts, which disrupts ABBP-2-Hsp70
      interaction, completely inhibits editing. ABBP-2 differs from previously
      described auxiliary proteins (ABBP-1, ACF, and GRY-RBP) in that it does not
      contain any RNA recognition motifs. Not only is ABBP-2 required for efficient
      apoB mRNA editing, this newly discovered apobec-1-binding protein may help
      determine the subcellular distribution and trafficking of apobec-1 via its
      interaction with the chaperonin Hsp70.

PMID- 11584024
TI  - T cell activity correlates with oligomeric peptide-major histocompatibility
      complex binding on T cell surface.
AB  - Recognition of virally infected cells by CD8+ T cells requires differentiation
      between self and nonself peptide-class I major histocompatibility complexes
      (pMHC). Recognition of foreign pMHC by host T cells is a major factor in the
      rejection of transplanted organs from the same species (allotransplant) or
      different species (xenotransplant). AHIII12.2 is a murine T cell clone that
      recognizes the xenogeneic (human) class I MHC HLA-A2.1 molecule (A2) and the
      syngeneic murine class I MHC H-2 D(b) molecule (D(b)). Recognition of both A2 and
      D(b) are peptide-dependent, and the sequences of the peptides recognized have
      been determined. Alterations in the antigenic peptides bound to A2 cause large
      changes in AHIII12.2 T cell responsiveness. Crystal structures of three
      representative peptides (agonist, null, and antagonist) bound to A2 partially
      explain the changes in AHIII12.2 responsiveness. Using class I pMHC octamers, a
      strong correlation is seen between T cell activity and the affinity of pMHC
      complexes for the T cell receptor. However, contrary to previous studies, we see
      similar half-lives for the pMHC multimers bound to the AHIII12.2 cell surface.

PMID- 11584026
TI  - Direct selection for paraquat resistance in Drosophila results in a different
      extended longevity phenotype.
AB  - When normal-lived Ra strain Drosophila were indirectly selected for longevity,
      they gave rise to long-lived La strain animals with lower oxidized protein and
      lipid levels that were temporally coincident with higher antioxidant activities.
      We wanted to determine whether it was possible to create long-lived animals by a
      direct selection for increased antioxidant activities. Using the same Ra strain,
      we selected them over 24 generations for increased resistance to paraquat.
      Selection was successful: the paraquat-resistant flies had a fourfold increase in
      their LT(50) (mean lethal time) values. Their extended longevity pattern differs
      from that of the La strain. The paraquat-resistant animals also have a lower
      level of antioxidant activity, an increased total P450 enzyme activity level, an
      altered pattern of energy metabolism, and a significantly lower developmental
      viability. We interpret these findings as suggesting that similar stress response
      phenotypes may be generated by different molecular mechanisms, some of which may
      generate very different types of extended longevity phenotypes.

PMID- 11584027
TI  - Age-related increase of brain cyclooxygenase activity and dietary modulation of
      oxidative status.
AB  - Several studies have demonstrated that inhibitors of cyclooxygenase (COX)
      attenuate various neuronal injuries and age-dependent demented conditions. From
      these findings, we proposed to test the effect of age on COX activity and its
      possible suppression by the antiaging action of dietary restriction in the rat
      brain. The status of reactive oxygen species (ROS) was also assessed to correlate
      with COX activity to delineate the underlying mechanism of the altered COX
      activity during aging. These results showed that COX activity significantly
      increased in 24-month-old rats compared with 6-month-old rats in an ad libitum
      group. Interestingly, mRNA and protein levels of COX-2 showed little
      corresponding age-related change. The formation of ROS was found to increase
      gradually with age in ad libitum fed rats. However, dietary restriction
      suppressed the increase at the age of 24 months. To substantiate the relationship
      between ROS and COX activity when the rats were 24 months of age, we conducted in
      vitro experiments with a C6 glioma cell line. Together, it is concluded that
      increased COX activity with age is due to the activation of COX catalytic
      reaction by ROS without increased gene expression of COX-2 and that it is related
      to the increased pro-oxidant status in aged rats.

PMID- 11584028
TI  - Have the oldest old adults ever been frail in the past? A hypothesis that
      explains modern trends in survival.
AB  - Three important results concerning the shape and the trends of the human
      mortality rate were discussed recently in demographic and epidemiological
      literature. These are the deceleration of the mortality rate at old ages, the
      tendency to rectangularization of the survival curve, and the decline of the old
      age mortality observed in the second part of the 20th century. In this paper we
      show that all these results can be explained by using a model with a new type of
      heterogeneity associated with individual differences in adaptive capacity. We
      first illustrate the idea of such a model by considering survival in a mixture of
      two subpopulations of individuals (called "labile" and "stable"). These
      subpopulations are characterized by different Gompertz mortality patterns, such
      that their mortality rates cross over. The survival chances of individuals in
      these subpopulations have different sensitivities to changes in environmental
      conditions. Then we develop a more comprehensive model in which the mortality
      rate is related to the adaptive capacity of an organism. We show that the trends
      in survival patterns experienced by a mixture of such individuals resemble those
      obtained in an analysis of empirical data on survival in developed countries.
      Lastly, we present evidence of the existence of subpopulations of phenotypes in
      both humans and experimental organisms, which were used as prototypes in our
      models. The existence of such phenotypes provides the possibility that at least
      part of today's centenarians originated from an initially frail part of the
      cohort.

PMID- 11584029
TI  - The interrelationship among muscle mass, strength, and the ability to perform
      physical tasks of daily living in younger and older women.
AB  - The purpose of this study was to objectively compare the difficulty and determine
      the contribution of strength and muscle mass to the performance of physical tasks
      of daily living in a group of younger and older women. A cross-sectional design
      was used. Volunteer participants were from the community of Birmingham, AL; there
      were 21 older (aged 60-75 years) and 20 younger (23-34 years) healthy women in
      the study. Subjects were matched for height and weight. Their testing included
      total and regional body composition evaluation by use of dual-energy x-ray
      absorptiometry, isometric strength tests of elbow flexors and knee extensors, and
      integrated electromyography (IEMG) evaluation while the subjects were standing
      from and sitting into a chair, and while they were carrying a small load (weight
      relative to strength). A two-way analysis of variance and a two-way analysis of
      covariance with repeated measures, Pearson product correlation, and first-order
      partial correlations were used to analyze the data. A significant inverse
      correlation was observed between age and isometric strength of both the knee
      extensors and elbow flexors. Adjusting for upper leg lean tissue did not change
      the significant inverse correlation between age and knee extensor strength.
      However, after an adjustment for arm lean tissue, there was no significant
      correlation between elbow flexor strength and age. Older women experienced
      significantly greater difficulty in standing than younger women as measured by
      quadriceps normalized IEMG (i.e., IEMG during task/IEMG during maximum isometric
      strength test). This difference persisted even after the covariate upper leg lean
      tissue was added to the model. No significant difference was observed between
      younger and older women for difficulty (biceps normalized IEMG) during the carry
      task after the covariate arm lean tissue was added to the model. The older women
      in this study had less strength in the knee extensors and experienced greater
      difficulty standing from a chair than the younger women, even after the covariate
      upper leg lean tissue was added to the model. This suggests that other factors,
      in addition to loss of lean tissue, contribute to the age-related decline of
      muscular strength and the ability to perform tasks with the legs. In contrast,
      although elbow flexor strength declined, this appeared to be largely due to
      decreased arm lean tissue mass.

PMID- 11584030
TI  - Exercise training eliminates age-related differences in skeletal muscle insulin
      receptor and IRS-1 abundance in rats.
AB  - Insulin resistance is common in old age, and exercise training can improve
      insulin sensitivity. The purpose of this study was to determine the influence of
      age (6 vs 26 months) and exercise training (10 weeks of treadmill running) on
      insulin signaling protein abundance in skeletal muscle from male Fisher 344 rats.
      Muscle levels of insulin receptor (IR), insulin receptor substrate-1 (IRS-1),
      phosphatidylinositol 3-kinase (PI3K), and Akt1, a serine-threonine kinase, were
      determined. IRS-1 was reduced with aging, IR and PI3K abundance was greater in
      old rats, and Akt1 was unchanged. IRS-1 was increased by training in old but not
      young rats, and IR was increased by training in young but not old rats. PI3K
      tended to increase and Akt1 did not change with training, regardless of age.
      Aging does not uniformly affect insulin signaling protein abundance, and exercise
      differentially alters IR and IRS-1 in young and old rats, thereby eliminating age
      related differences in these proteins.

PMID- 11584031
TI  - The critical link between health-related quality of life and age-related changes
      in physical activity and nutrition.

PMID- 11584032
TI  - The future history of home care and physician house calls in the United States.
AB  - Over the last 20 years, home care has experienced significant change. The home
      care industry developed into big business and a number of innovative models of
      home care were developed and evaluated. Although physicians perform many fewer
      house calls than a half-century ago, there has been a recent revival in house
      call training, education, and practice. In addition, telemedicine and other
      technologies hold great promise for the future of home care. However, the future
      history of home care will depend mostly on the ability of various stakeholders in
      the health care system to recognize the value of home care and develop and
      implement the appropriate incentives to encourage its proper place in the U.S.
      health care system.

PMID- 11584033
TI  - Walking difficulty, walking speed, and age as predictors of self-rated health:
      the women's health and aging study.
AB  - BACKGROUND: Older persons reporting disability are more likely to report poor
      self-rated health, but little work has been done to assess the independent
      relationships of reported walking difficulty and measured walking performance
      with self-rated health. This study examines the associations of walking
      difficulty, walking speed, and age with self-rated health in older women.
      METHODS: The data are from the baseline of the Women's Health and Aging Study.
      Difficulty walking one quarter mile was used as a measure of mobility in the
      representative population aged 65 and older screened for the study (n = 3841) and
      in the one third most disabled study group (n = 1002). Maximal walking speed was
      measured in the study sample. RESULTS: Increasing severity of walking difficulty
      (in the screened population and in the disabled study group), slower walking
      speed (in the study group), and younger age were all associated with fair or poor
      self-rated health, after simultaneous adjustment for these and other objective
      measures of physical performance and health. The associations of both measures of
      walking with self-rated health weakened with age. CONCLUSIONS: Both walking
      difficulty and walking speed are independent determinants of self-rated health.
      Adjusted for health and functioning, self-rated health tends to improve with age.

PMID- 11584034
TI  - Relationship between physiological loss, performance decrement, and age in master
      athletes.
AB  - BACKGROUND: The use of master athletes to describe an idealized rate of
      physiological loss associated with aging is quite common. The results of such
      studies suggest that older athletes may be able to reduce the rate of decline in
      functional loss. The findings of such studies have been questioned due to their
      limited sample size and the age range and gender of their subjects. METHODS: We
      examined a group of 146 male and 82 female master athletes over the age of 40
      years. Physiological parameters included maximal oxygen uptake (VO2max), body
      composition, muscle strength, bone density, and blood chemistries. Medical
      histories and training records were obtained via questionnaire. RESULTS: Results
      demonstrated gender differences in body composition, blood chemistries, blood
      pressure, VO2max, muscle strength, bone density, and performance (p <.05). All
      metabolic parameters for men and most for women demonstrated significant losses
      across the age range (p <.05). In addition, strength and performance for men and
      women and bone density for women declined significantly with age (p <.05). The
      demonstrated loss rates did not differ by gender. CONCLUSIONS: Although limited
      by the lack of a sedentary comparison group, these data suggest that age-related
      losses in VO2max may not be different from data previously reported for older
      sedentary adults and that loss in muscle strength and performance with aging is
      not linear.

PMID- 11584035
TI  - Choice stepping reaction time: a composite measure of falls risk in older people.
AB  - BACKGROUND: This study investigated the neuropsychological, sensorimotor, speed,
      and balance contributions to a new test of choice stepping reaction time (CSRT)
      and determined whether this new test is an important predictor of falls in older
      people. METHODS: A total of 477 retirement-village residents aged 62 to 95 years
      (mean +/- SD, 79.2 +/- 6.2 years) took the CSRT test, which required them to step
      onto one of four panels that were illuminated in a random order. The subjects
      also took tests that measured neuropsychological, sensorimotor, speed, and
      balance function. RESULTS: Multiple regression analysis revealed that poor
      performance in Part B of the Trail Making Test (a neuropsychological test) and
      impaired quadriceps strength, simple reaction time, sway with eyes open on a
      compliant surface, and maximal balance range were the best predictors of
      increased CSRTs (multiple r(2) =.45). Subjects with a history of falls had
      significantly increased CSRTs compared with nonfallers (1322 +/- 331 milliseconds
      and 1168 +/- 203 milliseconds, respectively). Impaired CSRT was a significant and
      independent predictor of falls, as were two complementary sensory measures
      (visual contrast sensitivity and lower limb proprioception). Of these measures,
      CSRT was the most important in predicting falls. Furthermore, the inclusion of
      CSRT in the model excluded measures of strength, central processing speed, and
      balance, because these could not provide nonredundant information for the
      prediction of falls. CONCLUSIONS: This study identifies a new test that provides
      a composite measure of falls risk in older people and elucidates the relative
      importance of specific physiological and neuropsychological systems in the
      initiation of fast and appropriate step responses.

PMID- 11584036
TI  - A population-based study on brain atrophy and motor performance in elderly women.
AB  - BACKGROUND: Brain atrophy is a common neuroimaging finding in healthy elderly
      individuals as well as in patients with movement-related disorders. The
      relationship between brain atrophy and motor changes has not been frequently
      reported. This study investigates this relationship. METHODS: A population-based
      sample of women (N = 238), aged 70, 74, and 78 years, living in Goteborg, Sweden,
      participated in this study. Motor performance was measured by a laboratory test,
      the Postural-Locomotion-Manual test, which precisely measures the subject's
      mobility of lower and upper extremities using an optoelectronic technique.
      Cortical and central atrophy were rated on computerized tomographic (CT) scans of
      the brain. RESULTS: In bivariate analysis, temporal lobe atrophy, high sylvian
      fissure ratio, and high bicaudate ratio were correlated with impaired mobility.
      The association between temporal lobe atrophy and high sylvian fissure ratio and
      poor mobility remained after controlling for age, smoking, coronary heart
      disease, diabetes mellitus, hypertension, and white matter lesions on CT scans.
      CONCLUSIONS: Our results suggest that temporal lobe atrophy, which is often seen
      on brain imaging in elderly persons, might be an important brain abnormality
      related to motor impairments in elderly women. Further studies to investigate
      this relationship and its underlying mechanisms are needed.

PMID- 11584037
TI  - The hierarchy of functional loss associated with cognitive decline in older
      persons.
AB  - OBJECTIVES: We studied a representative cohort of community-dwelling elderly
      persons to (i) examine the relationship between the loss of specific functional
      activities and cognitive status at the time of these losses, (ii) compare the
      cognitive status of participants who have and have not lost independence in these
      functional activities, and (iii) determine whether a hierarchical scale of
      functional loss is associated with declining cognitive status. METHODS: A cohort
      of 5874 community-dwelling persons aged 65 years and older from the Canadian
      Study of Health and Aging I and II were analyzed. At baseline and 5 years later,
      cognitive status with the Modified Mini-Mental State Examination (3MS) and
      functional status with 14 Older American Resources and Services (OARS) items were
      measured. For each OARS functional item, the mean 3MS scores for persons who lost
      independence during the 5-year period versus those who did not were compared.
      RESULTS: For each functional item, the 5-year decline in 3MS scores of persons
      who lost independence were significantly greater than those who remained
      independent (e.g., ability to do finances), with an 18-point decline for those
      who lost independence and a 2-point decline for those who retained independence.
      A hierarchy of functional items existed, with instrumental activities of daily
      living (ADLs) (e.g., shopping, banking, and cooking) being lost at higher
      cognitive scores than basic ADL items (e.g., eating, dressing, and walking),
      although there was some overlap. CONCLUSIONS: This is the first prospective study
      using a large representative cohort of elderly persons to demonstrate that
      progressive cognitive decline is associated with a specific pattern of loss of
      functional tasks. Clear cognitive thresholds at which development of dependency
      in OARS functional items occurred. By providing estimates of the cognitive status
      of persons at the time at which they developed dependency in specific functional
      items, a natural hierarchy of functional loss associated with cognitive decline
      emerged. For caregivers, clinicians, and health policy makers, this information
      can help anticipate the pattern of functional decline and the subsequent care
      needs of persons with declining cognition, potentially improving the quality of
      life of these persons and their caregivers and playing an important part in
      health care planning.

PMID- 11584038
TI  - Measuring higher level physical function in well-functioning older adults:
      expanding familiar approaches in the Health ABC study.
AB  - BACKGROUND: To evaluate development and progression of functional limitation and
      retain comparability with established approaches, we raised the measurement
      ceiling of commonly used self-report and performance-based measures of function.
      This study evaluated the utility and concurrent validity of these expanded
      measures. METHODS: The study population consisted of 3075 black and white men and
      women aged 70 to 79 years, with no reported mobility limitations or disability,
      participating in the Health, Aging, and Body Composition, or Health ABC study.
      Self-report measures were expanded by ascertaining ease of performance and
      including more demanding levels of some tasks. A single foot stand and narrow
      walk supplemented an established performance battery. For walking endurance, we
      developed the Long Distance Corridor Walk (LDCW), which includes distance covered
      in 2 minutes and the time to walk 400 m. RESULTS: The expanded self-report items
      identified one half of the men and one third of the women as exceptionally well
      functioning and 10% to 13% of men and 21% to 36% of women with lower capacity.
      The supplemented and rescored performance battery discriminated function over the
      full range. The LDCW further differentiated walking capacity at the high end and
      also identified a subgroup with limitations. The self-report and performance
      measures were significantly, but weakly, correlated (0.13-0.35) and were
      independent predictors of walking endurance. CONCLUSIONS: Well-functioning
      persons in their 70s exhibit a broad range of functional capacity readily
      ascertained by expanded self-report and performance tests. Significant
      associations among these measures support their concurrent validity, but
      generally weak correlations indicate they tap different, but important,
      dimensions of physical function.

PMID- 11584039
TI  - Use of alternative therapies in older outpatients in the United States and Japan:
      prevalence, reporting patterns, and perceived effectiveness.
AB  - BACKGROUND: The purpose of this study was to determine the prevalence, patterns
      of reporting, and perceived effectiveness of alternative medical therapies (ATs)
      among older white American, African American, and Japanese outpatients. METHODS:
      This study used a questionnaire to interview participants (N = 593; age, >59 y),
      who were outpatients of geriatric outpatient clinics in Saint Louis, Missouri,
      and Tokyo, Japan (white Americans, n = 180; African Americans, n = 106; and
      Japanese, n = 307). RESULTS: Use of >1 AT was greatest among older Japanese
      (74.3%), followed by white Americans (61.1%) and African Americans (47.2%; p
      <.001). The most common ATs used among the Japanese (and significantly more than
      the white and African American groups) were lifestyle diet, herbal therapy,
      massage, acupressure, and acupuncture. The white and African American groups were
      more frequent users of relaxation techniques and spiritual healing compared with
      the Japanese group. Contrary to prior studies of the general population, the use
      of >1 AT did not correlate with any sociodemographic variables. Reported use of
      ATs to doctors was low but similar in all three groups (white Americans = 48%,
      African Americans = 42%, and Japanese = 46%). Perceived effectiveness was high
      but similar in all three groups (white Americans = 85%, African Americans = 92%,
      and Japanese = 84%). Although chronic conditions were common reasons for use of
      ATs, nonmedical reasons (e.g., general health or religious reasons) were also
      common. CONCLUSIONS: Use of ATs was greater in Japan than in the United States,
      but for both countries, use by older persons was greater than previous reports of
      the general population. Because sociodemographic variables do not predict use,
      and reported use to doctors is low and perceived effectiveness is high, increased
      awareness and understanding about ATs by health care professionals seems
      imperative.

PMID- 11584040
TI  - Meal delivery practices do not meet needs of Alzheimer patients with increased
      cognitive and behavioral difficulties in a long-term care facility.
AB  - BACKGROUND: Alterations in circadian rhythms and behavioral difficulties likely
      impact meal consumption patterns in elderly individuals with probable Alzheimer's
      disease (AD). Despite these known changes, the profile of meals provided in the
      institution parallels the needs of younger, free-living, healthy populations.
      This investigation examined the impact of food delivery patterns on achieved
      intakes in elderly individuals with probable AD in a long-term care facility and
      how this relationship changes depending on time of day, body weight status,
      behavioral function, and cognitive ability. METHODS: Twenty-one consecutive days
      of investigator-weighed food intake and delivery collections were conducted on 25
      elderly individuals with probable AD who maintained the ability to self-feed.
      RESULTS: Energy consumed was positively associated with energy delivered for the
      majority of subjects, although the strength of this relationship varied across
      subjects and throughout the day. Energy delivered had the greatest impact on
      energy consumed at breakfast and the least impact at dinner in those with the
      greatest behavioral difficulties and cognitive impairment. Although those with
      low body mass indexes (BMIs) were likely to be delivered more energy, the impact
      of delivery on intakes decreased as energy delivered increased. CONCLUSIONS:
      Delivering excess energy to patients with poor BMIs likely does not result in
      increased energy consumption. Behavioral and cognitive deterioration leads to a
      shift in the time of day that energy delivered has an impact on energy
      consumption, with the most progressed individuals being most impacted by foods
      delivered in the morning, suggesting that traditional meal practices are
      inappropriate for elderly individuals with AD.

PMID- 11584041
TI  - Response to "Serum insulin-like growth factor-1 (IGF-1) in centenarians:
      implications of IGF-1 as a turnover protein".

PMID- 11584042
TI  - The expanding phenotype of laminin alpha2 chain (merosin) abnormalities: case
      series and review.
AB  - Initial reports of patients with laminin alpha2 chain (merosin) deficiency had a
      relatively homogeneous phenotype, with classical congenital muscular dystrophy
      (CMD) characterised by severe muscle weakness, inability to achieve independent
      ambulation, markedly raised creatine kinase, and characteristic white matter
      hypodensity on cerebral magnetic resonance imaging. We report a series of five
      patients with laminin alpha2 deficiency, only one of whom has this severe
      classical CMD phenotype, and review published reports to characterise the
      expanded phenotype of laminin alpha2 deficiency, as illustrated by this case
      series. While classical congenital muscular dystrophy with white matter
      abnormality is the commonest phenotype associated with laminin alpha2 deficiency,
      12% of reported cases have later onset, slowly progressive weakness more
      accurately designated limb-girdle muscular dystrophy. In addition, the following
      clinical features are reported with increased frequency: mental retardation
      (~6%), seizures (~8%), subclinical cardiac involvement (3-35%), and neuronal
      migration defects (4%). At least 25% of patients achieve independent ambulation.
      Notably, three patients with laminin alpha2 deficiency were asymptomatic, 10
      patients had normal MRI (four with LAMA2 mutations reported), and between 10-20%
      of cases had maximum recorded creatine kinase of less than 1000 U/l. LAMA2
      mutations have been identified in 25% of cases. Sixty eight percent of these have
      the classical congenital muscular dystrophy, but this figure is likely to be
      affected by ascertainment bias. We conclude that all dystrophic muscle biopsies,
      regardless of clinical phenotype, should be studied with antibodies to laminin
      alpha2. In addition, the use of multiple antibodies to different regions of
      laminin alpha2 may increase the diagnostic yield and provide some correlation
      with severity of clinical phenotype.

PMID- 11584043
TI  - A dominant gene for developmental dyslexia on chromosome 3.
AB  - Developmental dyslexia is a neurofunctional disorder characterised by an
      unexpected difficulty in learning to read and write despite adequate
      intelligence, motivation, and education. Previous studies have suggested mostly
      quantitative susceptibility loci for dyslexia on chromosomes 1, 2, 6, and 15, but
      no genes have been identified yet. We studied a large pedigree, ascertained from
      140 families considered, segregating pronounced dyslexia in an autosomal dominant
      fashion. Affected status and the subtype of dyslexia were determined by
      neuropsychological tests. A genome scan with 320 markers showed a novel dominant
      locus linked to dyslexia in the pericentromeric region of chromosome 3 with a
      multipoint lod score of 3.84. Nineteen out of 21 affected pedigree members shared
      this region identical by descent (corrected p<0.001). Previously implicated
      genomic regions showed no evidence for linkage. Sequencing of two positional
      candidate genes, 5HT1F and DRD3, did not support their role in dyslexia. The new
      locus on chromosome 3 is associated with deficits in all three essential
      components involved in the reading process, namely phonological awareness, rapid
      naming, and verbal short term memory.

PMID- 11584044
TI  - Frequency of mitochondrial transfer RNA mutations and deletions in 225 patients
      presenting with respiratory chain deficiencies.
AB  - OBJECTIVE: To evaluate the frequency of pathogenic mtDNA transfer RNA mutations
      and deletions in biochemically demonstrable respiratory chain (RC) deficiencies
      in paediatric and adult patients. METHODS: We screened for deletions and
      sequenced mitochondrial transfer RNA genes in skeletal muscle DNA from 225 index
      patients with clinical symptoms suggestive of a mitochondrial disorder and with
      biochemically demonstrable RC deficiency in skeletal muscle. RESULTS: We found
      pathogenic mitochondrial DNA mutations in 29% of the patients. The detection rate
      was significantly higher in adults (48%) than in the paediatric group (18%). Only
      one pathogenic mutation was detected in the neonatal group. In addition, we
      describe seven novel transfer RNA sequence variations with unknown pathogenic
      relevance (six homoplasmic and one heteroplasmic) and 13 homoplasmic
      polymorphisms. One heteroplasmic transfer RNA(Leu(UUR)) A>G mutation at position
      3274 is associated with a distinct neurological syndrome. CONCLUSIONS: We provide
      an estimation of the frequency of mitochondrial transfer RNA mutations and
      deletions in paediatric and adult patients with respiratory chain deficiencies.

PMID- 11584045
TI  - An epidemiological study of Wolf-Hirschhorn syndrome: life expectancy and cause
      of mortality.
AB  - OBJECTIVE: Early research into Wolf-Hirschhorn syndrome (WHS) described a high
      mortality and no relationship between deletion size and phenotype. This may need
      to be revised in the light of improved cytogenetic resolution and medical care.
      We have collected epidemiological data to allow the calculation of birth
      incidence and mortality figures. In addition, we have investigated the
      possibility of a relationship between deletion size and mortality. METHOD:
      Information relating to past and present cases diagnosed in the UK was collected
      by multiple ascertainment. RESULTS: A total of 159 cases were collected. The
      status (alive or dead) was determined for 146, of whom 96 are alive, 37 had died,
      and 13 were detected on prenatal diagnostic tests. A minimum birth incidence of 1
      in 95 896 was calculated. The crude infant mortality rate was 17% (23/132) and in
      the first two years of life the mortality rate was 21% (28/132). Cases with large
      de novo deletions (proximal to and including p15.2) were more likely to have died
      than those with smaller deletions (odds ratio=5.7, 95% CI=1.7-19.9) after
      adjusting for age. A comparison of survival curves for de novo deletions and
      translocations did not show a statistically significant difference (p=0.11). The
      median survival time for de novo deletions was 34+ years while for translocation
      cases it was 18+ years. CONCLUSIONS: The mortality rate is lower than previously
      reported. There is a statistically significant relationship between deletion size
      and overall risk of death in de novo deletion cases. The difference in survival
      curves between de novo deletions and translocations is not statistically
      significant.

PMID- 11584047
TI  - The Asp1822Val variant of the APC gene is a common polymorphism without clinical
      implications.

PMID- 11584046
TI  - Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze
      paresis and dementia, maps to 1p36.
AB  - Kufor-Rakeb syndrome is an autosomal recessive nigro-striatal-pallidal-pyramidal
      neurodegeneration. The onset is in the teenage years with clinical features of
      Parkinson's disease plus spasticity, supranuclear upgaze paresis, and dementia.
      Brain scans show atrophy of the globus pallidus and pyramids and, later,
      widespread cerebral atrophy. We report linkage in Kufor-Rakeb syndrome to a 9 cM
      region of chromosome 1p36 delineated by the markers D1S436 and D1S2843, with a
      maximum multipoint lod score of 3.6.

PMID- 11584048
TI  - A simple non-isotopic method to show pitfalls during mutation analysis of the
      glucocerebrosidase gene.

PMID- 11584049
TI  - No evidence of allelic heterogeneity in the DYT1 gene of European patients with
      early onset torsion dystonia.

PMID- 11584050
TI  - Autosomal recessive non-syndromic hearing loss in the Lebanese population:
      prevalence of the 30delG mutation and report of two novel mutations in the
      connexin 26 (GJB2) gene.

PMID- 11584051
TI  - Cancer, DNA repair mechanisms, and resistance to chemotherapy.

PMID- 11584052
TI  - Future for ovarian cancer screening: novel markers from emerging technologies of
      transcriptional profiling and proteomics.

PMID- 11584053
TI  - Examining IRBs: are review boards fulfilling their duties?

PMID- 11584054
TI  - Biomedical research 'revolution' drives push for balanced funding.

PMID- 11584055
TI  - Looking abroad: do funding imbalances affect foreign competition?

PMID- 11584056
TI  - Cancer incidence trends differ between Europe, United States.

PMID- 11584057
TI  - What is the promise of embryonic stem cell research?

PMID- 11584060
TI  - Selective estrogen receptor modulation and reduction in risk of breast cancer,
      osteoporosis, and coronary heart disease.
AB  - The recognition of selective estrogen receptor modulation in the laboratory has
      resulted in the development of two selective estrogen receptor modulators
      (SERMs), tamoxifen and raloxifene, for clinical application in healthy women.
      SERMs are antiestrogenic in the breast but estrogen-like in the bones and reduce
      circulating cholesterol levels. SERMs also have different degrees of
      estrogenicity in the uterus. Tamoxifen is used specifically to reduce the
      incidence of breast cancer in premenopausal and postmenopausal women at risk for
      the disease. In contrast, raloxifene is used specifically to reduce the risk of
      osteoporosis in postmenopausal women at high risk for osteoporosis. The study of
      tamoxifen and raloxifene (STAR) trial is currently comparing the ability of these
      SERMs to reduce breast cancer incidence in high-risk postmenopausal women. There
      is intense interest in understanding the molecular mechanism(s) of action of
      SERMs at target sites in a woman's body. An understanding of the targeted actions
      of this novel drug group will potentially result in the introduction of new
      multifunctional medicines with applications as preventive agents or treatments of
      breast cancer and endometrial cancer, coronary heart disease, and osteoporosis.

PMID- 11584061
TI  - Prostasin, a potential serum marker for ovarian cancer: identification through
      microarray technology.
AB  - BACKGROUND: Screening biomarkers for ovarian cancer are needed because of its
      late stage at diagnosis and poor survival. We used microarray technology to
      identify overexpressed genes for secretory proteins as potential serum biomarkers
      and selected prostasin, a serine protease normally secreted by the prostate
      gland, for further study. METHODS: RNA was isolated and pooled from three ovarian
      cancer cell lines and from three normal human ovarian surface epithelial (HOSE)
      cell lines. Complementary DNA generated from these pools was hybridized to a
      microarray slide, and genes overexpressed in the cancer cells were identified.
      Real-time quantitative polymerase chain reaction was used to examine prostasin
      gene expression in ovarian cancer and HOSE cell lines. Anti-prostasin antibodies
      were used to examine prostasin expression and to measure serum prostasin by an
      enzyme-linked immunosorbent assay in 64 case patients with ovarian cancer and in
      137 control subjects. Previously determined levels of CA 125, an ovarian cancer
      marker, were available from about 70% of all subjects. All statistical tests were
      two-sided. RESULTS: Prostasin was detected by immunostaining more strongly in
      cancerous ovarian epithelial cells and stroma than in normal ovarian tissue. The
      mean level of serum prostasin was 13.7 microg/mL (95% confidence interval [CI] =
      10.5 to 16.9 microg/mL) in 64 case patients with ovarian cancer and 7.5 microg/mL
      (95% CI = 6.6 to 8.3 microg/mL) in 137 control subjects (P<.001, after adjustment
      for the subject's age, year of collection, and specimen quality). In 14 of 16
      case patients with both preoperative and postoperative serum samples,
      postoperative prostasin levels were statistically significantly lower than
      preoperative levels (P =.004). In 37 case patients with nonmucinous ovarian
      cancer and in 100 control subjects for whom levels of CA 125 and prostasin were
      available, the combination of markers gave a sensitivity of 92% (95% CI = 78.1%
      to 98.3%) and a specificity of 94% (95% CI = 87.4% to 97.7%) for detecting
      ovarian cancer. CONCLUSIONS: Prostasin is overexpressed in epithelial ovarian
      cancer and should be investigated further as a screening or tumor marker, alone
      and in combination with CA 125.

PMID- 11584062
TI  - Susceptibility of nonpromoter CpG islands to de novo methylation in normal and
      neoplastic cells.
AB  - BACKGROUND: Many cancers display alterations in methylation patterns of CpG
      islands--stretches of DNA rich in CpG dinucleotides often associated with gene
      promoters that are involved in initiation of gene transcription. This methylation
      may perturb expression of genes critical to the regulation of cell proliferation.
      Aberrant methylation is not limited to a few genes or to promoter regions but has
      been found on a genome-wide scale in a variety of neoplasias, including
      colorectal cancer and acute myelogenous leukemia. Our goal was to characterize,
      in a quantitative manner, the profiles of abnormally methylated genes that may be
      specific for different cancers. METHODS: Using a quantitative assay, methylation
      sensitive single nucleotide primer extension (MS-SNuPE), we have analyzed the
      methylation levels of promoter and exonic (coding region) CpG islands of two
      cyclin-dependent kinase inhibitors [p15(INK4B) and p16(INK4A)] and the PAX6 gene,
      which encodes a transcriptional factor involved in neuronal proliferation, in DNA
      samples taken from patients with chronic myelogenous leukemia, acute myelogenous
      leukemia, myelodysplastic syndrome, and colorectal cancer. RESULTS: De novo
      methylation of all three exonic loci in tumors--relative to baseline levels found
      in nontumor tissue or blood--was observed in hematologic neoplasias and in solid
      tumors as well as in normal colonic tissue. However, methylation of promoter
      regions was more limited. Moreover, two different patterns of promoter
      methylation distinguished the leukemias from colorectal cancer: p15 promoter
      hypermethylation was found only in the leukemias, and p16 promoter
      hypermethylation occurred only in colon tumors. However, we did not address this
      issue prospectively; therefore, such an observation is only hypothesis
      generating. CONCLUSIONS: The methylation patterns that we observed suggest that
      exonic CpG islands are more susceptible to de novo methylation than promoter
      islands and that methylation may be seeded in exonic regions, from which it can
      spread to other islands, including promoter regions. Subsequent selection of
      cells with a growth advantage conferred by spread of methylation into and
      inactivation of a particular promoter might then contribute to the genesis of a
      specific type of cancer.

PMID- 11584063
TI  - In vitro evidence for homologous recombinational repair in resistance to
      melphalan.
AB  - BACKGROUND: The generation of DNA interstrand cross-links is thought to be
      important in the cytotoxicity of nitrogen mustard alkylating agents, such as
      melphalan, which have antitumor activity. Cell lines with mutations in
      recombinational repair pathways are hypersensitive to nitrogen mustards. Thus,
      resistance to melphalan may require accelerated DNA repair by either
      recombinational repair mechanisms involving Rad51-related proteins (including x
      ray repair cross-complementing proteins Xrcc2, Xrcc3, and Rad52) or by
      nonhomologous endjoining involving DNA-dependent protein kinase (DNA-PK) and Ku
      proteins. We investigated the role of DNA repair in melphalan resistance in
      epithelial tumor cell lines. METHODS: Melphalan cytotoxicity was determined in 14
      epithelial tumor cell lines by use of the sulforhodamine assay. Homologous
      recombinational repair involving Rad51-related proteins was investigated by
      determining the levels of Rad51, Rad52, and Xrcc3 proteins and the density of
      nuclear melphalan-induced Rad51 foci, which represent sites of homologous
      recombinational repair. Nonhomologous endjoining was investigated by determining
      the levels of Ku70 and Ku86 proteins and DNA-PK activity. Linear regression
      analysis was used to analyze correlations between the various protein levels, DNA
      PK activity, or Rad51 foci formation and melphalan cytotoxicity. All statistical
      tests were two-sided. RESULTS: Melphalan resistance was correlated with Xrcc3
      levels (r =.587; P =.027) and the density of melphalan-induced Rad51 foci (r
      =.848; P =.008). We found no correlation between melphalan resistance and Rad51,
      Rad52, or Ku protein levels or DNA-PK activity. CONCLUSION: Correlations of
      melphalan resistance in epithelial tumor cell lines with Xrcc3 protein levels and
      melphalan-induced Rad51 foci density suggest that homologous recombinational
      repair is involved in resistance to this nitrogen mustard.

PMID- 11584064
TI  - Familial multiple myeloma: a family study and review of the literature.
AB  - BACKGROUND: The etiology of multiple myeloma (MM) remains obscure, although
      reports of familial clustering have implicated both a host susceptibility factor
      and environmental effects. Here we describe the medical histories of members of a
      family prone to MM. METHODS: We developed a pedigree for an MM-prone family by
      using information obtained from a questionnaire. Protein immunoelectrophoresis of
      serum and urine from the proband and from 19 family members was performed to
      detect monoclonal immunoproteins. Peripheral blood obtained from the proband and
      from five relatives was subjected to standard cytogenetic studies to detect
      constitutional chromosomal abnormalities. Multifluor-fluorescence in situ
      hybridization (M-FISH) and standard FISH studies were performed on peripheral
      blood from the proband and from two other affected living relatives to determine
      their karyotypes and to detect clonal chromosomal abnormalities frequently seen
      in patients with MM. RESULTS: Within this family, a sibship of seven included
      three individuals (including the proband) with histologically verified MM and two
      individuals with a monoclonal gammopathy of unknown significance (MGUS), as
      determined by immunoelectrophoresis of serum and urine. This family also had
      members with acute lymphocytic leukemia, malignant melanoma, and prostate cancer.
      In the family members tested, we detected no constitutional chromosomal
      abnormality. None of the three individuals analyzed by FISH had a deletion of the
      retinoblastoma (Rb-1) locus, which is frequently deleted in patients with MM, and
      only one (the proband) had a translocation involving chromosomes 11 and 14, a
      clonal abnormality commonly seen in MM. CONCLUSION: The study of familial MM may
      provide insights into the pathogenesis and, ultimately, the control and
      prevention of MM and related disorders.

PMID- 11584065
TI  - Complexity of lung cancer modifiers: mapping of thirty genes and twenty-five
      interactions in half of the mouse genome.
AB  - BACKGROUND: Numerous low-penetrance genes control susceptibility to cancer in
      experimental animals, but the overall genetic information on this group of genes
      (i.e., number of loci and their mutual interactions) is missing. We performed a
      systematic search, scanning roughly half of the mouse genome for lung cancer
      susceptibility (Sluc) genes affecting tumor size or number by using mouse
      recombinant congenic (RC) strains. In each RC strain (OcB), approximately 12.5%
      of the genome is derived from the lung cancer-resistant strain B10.O20, whereas
      the rest is derived from the lung cancer-susceptible strain O20. METHODS: A total
      of 730 F2 hybrids from five (OcB x O20) crosses were tested. Pregnant mice were
      treated on day 18 of gestation with a single dose of N-ethyl-N-nitrosourea. When
      offspring were 16 weeks old, whole lungs were removed and sectioned semiserially,
      and the size of all lung tumors (n = 2658) was determined. Analysis of variance
      was used for detection of linkage, and models (including main effect and two-way
      interactions) were tested with a statistical program. RESULTS: We detected a
      total of 30 Sluc loci (16 new plus 14 previously reported) and 25 two-way
      interactions. Some of these interactions are counteracting (e.g., Sluc17 and
      Sluc20), resulting in the partial or total masking of the individual independent
      effect (main effect) of each involved locus. Seven loci (Sluc1, Sluc5, Sluc12,
      Sluc16, Sluc18, Sluc20, and Sluc26) and two interactions (Sluc5 x Sluc12 and
      Sluc5 x Sluc26) were detected in more than one RC strain. CONCLUSIONS: The
      extrapolation of our results to the whole genome suggests approximately 60 Sluc
      loci (90% confidence intervals = 42 to 78). Despite the genetic complexity of
      lung cancer, use of appropriate mapping strategies can identify a large number of
      responsible loci and can reveal their interactions. This study provides an
      insight into the genetic control of lung tumorigenesis and may serve as a
      paradigm for investigating the genetics of other cancer types.

PMID- 11584067
TI  - Re: Biomarker risk assessment and bladder cancer detection in a cohort exposed to
      benzidine.

PMID- 11584068
TI  - Re: Five versus more than five years of tamoxifen for lymph node-negative breast
      cancer: updated findings from the National Surgical Adjuvant Breast and Bowel
      Project B-14 Randomized Trial.

PMID- 11584069
TI  - Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear
      conditioning.
AB  - Fear conditioning is a form of associative learning in which subjects come to
      express defense responses to a neutral conditioned stimulus (CS) that is paired
      with an aversive unconditioned stimulus (US). Considerable evidence suggests that
      critical neural changes mediating the CS-US association occur in the lateral
      nucleus of the amygdala (LA). Further, recent studies show that associative long
      term potentiation (LTP) occurs in pathways that transmit the CS to LA, and that
      drugs that interfere with this LTP also disrupt behavioral fear conditioning when
      infused into the LA, suggesting that associative LTP in LA might be a mechanism
      for storing memories of the CS-US association. Here, we develop a detailed
      cellular hypothesis to explain how neural responses to the CS and US in LA could
      induce LTP-like changes that store memories during fear conditioning.
      Specifically, we propose that the CS evokes EPSPs at sensory input synapses onto
      LA pyramidal neurons, and that the US strongly depolarizes these same LA neurons.
      This depolarization, in turn, causes calcium influx through NMDA receptors
      (NMDARs) and also causes the LA neuron to fire action potentials. The action
      potentials then back-propagate into the dendrites, where they collide with CS
      evoked EPSPs, resulting in calcium entry through voltage-gated calcium channels
      (VGCCs). Although calcium entry through NMDARs is sufficient to induce synaptic
      changes that support short-term fear memory, calcium entry through both NMDARs
      and VGCCs is required to initiate the molecular processes that consolidate
      synaptic changes into a long-term memory.

PMID- 11584070
TI  - Brain activity during the encoding, retention, and retrieval of stimulus
      representations.
AB  - Studies of delayed nonmatching-to-sample (DNMS) performance following lesions of
      the monkey cortex have revealed a critical circuit of brain regions involved in
      forming memories and retaining and retrieving stimulus representations. Using
      event-related functional magnetic resonance imaging (fMRI), we measured brain
      activity in 10 healthy human participants during performance of a trial-unique
      visual DNMS task using novel barcode stimuli. The event-related design enabled
      the identification of activity during the different phases of the task (encoding,
      retention, and retrieval). Several brain regions identified by monkey studies as
      being important for successful DNMS performance showed selective activity during
      the different phases, including the mediodorsal thalamic nucleus (encoding),
      ventrolateral prefrontal cortex (retention), and perirhinal cortex (retrieval).
      Regions showing sustained activity within trials included the ventromedial and
      dorsal prefrontal cortices and occipital cortex. The present study shows the
      utility of investigating performance on tasks derived from animal models to
      assist in the identification of brain regions involved in human recognition
      memory.

PMID- 11584071
TI  - Impaired auditory recognition memory in amnesic patients with medial temporal
      lobe lesions.
AB  - Two tests of auditory recognition memory were given to four patients with
      bilateral hippocampal damage (H+) and three patients with large medial temporal
      lobe lesions and additional variable damage to lateral temporal cortex (MTL+).
      When single stimuli were presented, performance was normal across delays as long
      as 30 sec, presumably because information could be maintained in working memory
      through rehearsal. When lists of 10 stimuli were presented, performance was
      impaired after a 5-min delay. Patients with MTL+ lesions performed marginally
      worse than patients with H+ lesions, consistent with findings for recognition
      memory in other modalities. The findings show that auditory recognition, like
      recognition memory in other sensory modalities, is dependent on the medial
      temporal lobe.

PMID- 11584072
TI  - Neonatal exposure to novel environment enhances hippocampal-dependent memory
      function during infancy and adulthood.
AB  - Early life experience affects behavior and brain mechanisms. Handling rats during
      the first three weeks in life can slow age-related cognitive decline (as measured
      by a hippocampal-dependent spatial learning task) and reduce age-related
      hippocampal neuron loss. It is not clear, however, whether this early
      environmental influence on learning is selective for old age or is more general,
      affecting cognitive development during infancy and young adulthood as well. We
      briefly exposed neonatal rats to a novel non-home environment for 3 min daily
      during the first three weeks of life (as a component of the handling method). We
      found that this brief early environmental manipulation resulted in enhanced
      hippocampal-dependent learning immediately after weaning and that this learning
      enhancement persisted into adulthood. These results suggest that subtle early
      life events can affect cognitive development in all developmental stages and that
      changes in neural mechanisms other than neuron number are likely to mediate the
      learning enhancement at multiple developmental stages.

PMID- 11584073
TI  - Differential effects of PACAP-38 on synaptic responses in rat hippocampal CA1
      region.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP-38) is a member of the
      vasointestinal polypeptide (VIP)/secretin/glucagon family of neuropeptides for
      which neuroregulatory functions have been postulated. PACAP-38 receptors are
      expressed in different brain regions, including hippocampus. In this study, we
      examined the dose-dependent effects of PACAP-38 on the excitatory postsynaptic
      field potential (fEPSP) evoked at the Schaffer collateral-CA1 synapse in rat
      hippocampal slices. Bath application of low dose (0.05 nM) of PACAP-38 induced
      long-lasting facilitation of the fEPSP. This enhancement was blocked by the
      cholinergic receptor antagonist atropine and partially by the NMDA receptor
      antagonist 2-amino-5-phosphonovalerate (APV) and therefore, shares a common
      mechanism with LTP. In contrast, a high dose (1 microM) of PACAP-38 induced a
      persistent depression of the fEPSP that was not blocked by antagonists of
      cholinergic receptors (i.e., atropine and mecamylamine), adenosine receptors
      (i.e., DCPCX), or glutamatergic NMDA receptors (APV). Intermediate doses (0.1-0.5
      microM) of PACAP-38 produced an initial decrease of the fEPSP followed by an
      enhancement. This decrease was not blocked by atropine whereas the facilitation
      was. These results show that PACAP-38 modulates CA1 synaptic transmission in a
      dose-dependent manner and that the peptide interacts with cholinergic and
      glutamatergic systems.

PMID- 11584074
TI  - Impaired conditioned taste aversion learning in spinophilin knockout mice.
AB  - Plasticity in dendritic spines may underlie learning and memory. Spinophilin, a
      protein enriched in dendritic spines, has the properties of a scaffolding protein
      and is believed to regulate actin cytoskeletal dynamics affecting dendritic spine
      morphology. It also binds protein phosphatase-1 (PP-1), an enzyme that regulates
      dendritic spine physiology. In this study, we tested the role of spinophilin in
      conditioned taste aversion learning (CTA) using transgenic spinophilin knockout
      mice. CTA is a form of associative learning in which an animal rejects a food
      that has been paired previously with a toxic effect (e.g., a sucrose solution
      paired with a malaise-inducing injection of lithium chloride). Acquisition and
      extinction of CTA was tested in spinophilin knockout and wild-type mice using
      taste solutions (sucrose or sodium chloride) or flavors (Kool-Aid) paired with
      moderate or high doses of LiCl (0.15 M, 20 or 40 mL/kg). When sucrose or NaCl
      solutions were paired with a moderate dose of LiCl, spinophilin knockout mice
      were unable to learn a CTA. At the higher dose, knockout mice acquired a CTA but
      extinguished more rapidly than wild-type mice. A more salient flavor stimulus
      (taste plus odor) revealed similar CTA learning at both doses of LiCl in both
      knockouts and wild types. Sensory processing in the knockouts appeared normal
      because knockout mice and wild-type mice expressed identical unconditioned taste
      preferences in two-bottle tests, and identical lying-on-belly responses to acute
      LiCl. We conclude that spinophilin is a candidate molecule required for normal
      CTA learning.

PMID- 11584075
TI  - Scopolamine enhances generalization between odor representations in rat olfactory
      cortex.
AB  - Acetylcholine (ACh) has a critical, modulatory role in plasticity in many sensory
      systems. In the rat olfactory system, both behavioral and physiological data
      indicate that ACh may be required for normal odor memory and synaptic plasticity.
      Based on these data, neural network models have hypothesized that ACh muscarinic
      receptors reduce interference between learned cortical representations of odors
      within the piriform cortex. In this study, odor receptive fields of rat anterior
      piriform cortex (aPCX) single-units for alkane odors were mapped before and after
      either a systemic injection of the muscarinic receptor antagonist scopolamine
      (0.5 mg/kg) or aPCX surface application of 500 microM scopolamine (or saline/ACSF
      controls). Cross-habituation between alkanes differing by two to four carbons was
      then examined following a 50-sec habituating stimulus. The results demonstrate
      that neither aPCX spontaneous activity nor odor-evoked activity (receptive field)
      was affected by scopolamine, but that cross-habituation in aPCX neurons was
      enhanced significantly by either systemic or cortical scopolamine. These results
      indicate that scopolamine selectively enhances generalization between odor
      representations in aPCX in a simple memory task. Given that ACh primarily affects
      intracortical association fibers in the aPCX, the results support a role for the
      association system in odor memory and discrimination and indicate an important
      ACh modulatory control over this basic sensory process.

PMID- 11584076
TI  - Side-specificity of olfactory learning in the honeybee: generalization between
      odors and sides.
AB  - Honeybees (Apis mellifera) can be trained to associate an odor stimulus with a
      sucrose reward. The neural structures involved in the detection and integration
      of olfactory stimuli are represented bilaterally in the brain. Little is known
      about the respective roles of the two sides of the brain in olfactory learning.
      Does each side learn independently of the other, or do they communicate, and if
      so, to what extent and at what level of neural integration? We addressed these
      questions using the proboscis extension response (PER) conditioning paradigm
      applied in a preparation that allows the separation of the two input sides during
      olfactory stimulations. Bees conditioned to two odorants A and B, one being
      learned on each side (A+/B+ training), showed in extinction tests rather
      unspecific responses: They responded to both odorants on both sides. This could
      be attributable to either a transfer of the learned information between sides, or
      to a generalization between odorants on each side. By subjecting bees to
      conditioning on one side only (A+/0 training), we found that the learned
      information is indeed transferred between sides. However, when bees were trained
      explicitly to give opposite values to the two odorants on the two sides (A+B-/B+A
      training), they showed clear side-specific response patterns to these odorants.
      These results are used in the elaboration of a functional model of laterality of
      olfactory learning and memory processing in the honeybee brain.

PMID- 11584077
TI  - Superior formation of cortical memory traces for melodic patterns in musicians.
AB  - The human central auditory system has a remarkable ability to establish memory
      traces for invariant features in the acoustic environment despite continual
      acoustic variations in the sounds heard. By recording the memory-related mismatch
      negativity (MMN) component of the auditory electric and magnetic brain responses
      as well as behavioral performance, we investigated how subjects learn to
      discriminate changes in a melodic pattern presented at several frequency levels.
      In addition, we explored whether musical expertise facilitates this learning. Our
      data show that especially musicians who perform music primarily without a score
      learn easily to detect contour changes in a melodic pattern presented at variable
      frequency levels. After learning, their auditory cortex detects these changes
      even when their attention is directed away from the sounds. The present results
      thus show that, after perceptual learning during attentive listening has taken
      place, changes in a highly complex auditory pattern can be detected automatically
      by the human auditory cortex and, further, that this process is facilitated by
      musical expertise.

PMID- 11584078
TI  - Molecular mechanisms of sterol absorption.
AB  - Recent studies have significantly advanced our understanding of intestinal sterol
      absorption at the molecular level. Nuclear hormone receptors (such as liver X
      receptor, farnesoid X receptor and retinoid X receptor) regulate the absorption
      of dietary sterols by modulating the transcription of several important genes
      involved in cholesterol metabolism. One of these genes encodes a molecule
      [adenosine triphosphate-binding cassette (ABC) transporter] that transports
      dietary cholesterol from enterocytes back out to the intestinal lumen, thereby
      limiting the amount of cholesterol absorbed. ABC transporters also provide an
      efficient barrier against the absorption of plant sterols. Another key process
      that affects intestinal sterol absorption is the synthesis of cholesterol esters.
      Mice lacking the enzyme for cholesterol esterification in the small intestine
      have a reduced capacity to absorb dietary cholesterol and are protected against
      diet-induced hypercholesterolemia and gallstone formation. In addition to
      elucidating some of the molecular mechanisms of sterol absorption, these recent
      findings may lead to new therapeutic options to treat hypercholesterolemia.

PMID- 11584079
TI  - Novel tocotrienols of rice bran inhibit atherosclerotic lesions in C57BL/6 ApoE
      deficient mice.
AB  - We are studying novel tocotrienols, which have a number of activities that might
      interfere with the formation of atherosclerotic plaques, including
      hypocholesterolemic, antioxidant, anti-inflammatory and antiproliferation
      effects. This study compared the effects of alpha-tocopherol, the tocotrienol
      rich fraction (TRF(25)) and didesmethyl tocotrienol (d-P(25)-T3) of rice bran on
      the pathogenesis of atherosclerotic lesions in C57BL/6 apolipoprotein (apo)E
      deficient (-/-) mice. These mice are an excellent model because they become
      hyperlipidemic even when they consume a low fat diet and they develop complex
      atherosclerotic lesions similar to those of humans. These compounds were also
      tested in wild-type C57BL/6 apoE (+/+) and (+/-) mice fed low or high fat diets.
      When a high fat diet was supplemented with alpha-tocopherol, TRF(25) or d-P(25)
      T3 and fed to mice (+/+) for 24 wk, atherosclerotic lesion size was reduced 23%
      (P = 0.33), 36% (P = 0.14) and 57% (P < 0.02), respectively, and in mice (+/-)
      fed for 18 wk, lesions were reduced by 19% (P = 0.15), 28% (P < 0.01) and 33% (P
      < 0.005), respectively, compared with mice fed a control diet. A low fat diet did
      not cause atherosclerotic lesions in these mice. The low fat diet supplemented
      with TRF(25) or d-P(25)-T3 fed to apoE-deficient (-/-) mice for 14 wk decreased
      atherosclerotic lesion size by 42% (P < 0.04) and 47% (P < 0.01), respectively,
      whereas alpha-tocopherol supplementation resulted in only an 11% (P = 0.62)
      reduction. These results demonstrate the superior efficacy of tocotrienols
      compared with alpha-tocopherol. Although tocotrienols decreased serum
      triglycerides, total and LDL cholesterol levels, the decreases in atherosclerotic
      lesions seem to be due to the other activities. Serum tocol concentrations in
      various groups are also described. This is the first report of a significant
      reduction in the atherosclerotic lesion size in all three genotypes of apoE mice
      fed a novel tocotrienol (d-P(25)-T3) of rice bran. Dietary tocotrienol
      supplements may provide a unique approach to promoting cardiovascular health.

PMID- 11584080
TI  - Administration of raw onion inhibits platelet-mediated thrombosis in dogs.
AB  - A number of studies suggest that dietary intake of onions is of benefit to
      cardiovascular health. Onion juice inhibits in vitro human platelet aggregation.
      To study the in vivo effect of onion on platelet aggregation, 11 dogs were
      prepared with mechanically damaged and stenosed coronary arteries. Periodic
      platelet-mediated thrombus formation followed by embolization produced cyclic
      flow reductions (CFR). In five dogs, 0.09 +/- 0.01 mL/kg onion juice administered
      intravenously abolished CFR within 20 min. This was followed by a 60 +/- 14% (P =
      0.002) reduction in collagen-induced ex vivo whole-blood platelet aggregation.
      Six dogs were given 2.0 g/kg raw onion homogenate intragastrically. CFR were
      eliminated within 2.5-3 h in five of the dogs. This was accompanied by a 44 +/-
      24% (P = 0.04) reduction in ex vivo aggregation. These findings suggest that the
      consumption of raw onion may help prevent platelet-mediated cardiovascular
      disorders. However, in vitro incubations of onion juice demonstrated that the
      platelet inhibitory response was significantly greater in dog blood than in human
      blood.

PMID- 11584081
TI  - Characterization of the genomic structure of the human vitamin C transporter
      SVCT1 (SLC23A2).
AB  - Vitamin C (L-ascorbic acid), a critical cofactor for intracellular enzymatic
      reactions, functions as a scavenger of free oxygen radicals and is an essential
      micronutrient. Vitamin C is actively transported into cells by one of two closely
      related sodium-dependent transporters, SVCT1 or SVCT2. In this paper, we report
      the complete sequencing and gene structure of SLC23A2, the gene encoding SVCT1.
      The1797-bp cDNA sequence (open reading frame) of the SLC23A2 gene was derived
      from a compact genomic sequence of 7966 bp [translation initiation codon (ATG) to
      poly A tail], which is divided into 14 exons. Furthermore, repetitive or masked
      elements constituted 17.98% of the gene; there were 4 Alu sequences and 5 MIR
      (Mammalian Interspersed Repetitive element) sequences. A search for common
      variants in SLC23A2, using current bioinformatic tools and direct resequencing of
      control populations, failed to identify common single nucleotide polymorphisms.
      The start of transcription was mapped to a position -47 relative to the ATG; the
      immediate 5' sequence was determined and analyzed for possible consensus binding
      sites for known transcription factors. Our findings will serve as the foundation
      for investigation of the regulation and expression of the tissue-specific sodium
      dependent vitamin C transporter, SLC23A2.

PMID- 11584082
TI  - Retinoic acid and lipopolysaccharide act synergistically to increase prostanoid
      concentrations in rats in vivo.
AB  - Vitamin A and its active metabolite retinoic acid (RA) modulate host-pathogen
      interactions by interfering with the host immune and inflammatory response
      including prostaglandin (PG) biosynthesis. The effects of RA on phospholipase
      A(2) (PLA(2)) and cyclooxygenase (COX) isoforms in vitro are controversial, and
      few in vivo studies exist. We investigated the in vivo effects of RA on PG
      biosynthesis in the presence or absence of lipopolysaccharide (LPS) in rats. RA
      alone [10 mg/(kg. d) for 5 d] increased plasma and liver PG concentrations by
      increasing COX-1 protein expression (twofold that of control rats). RA acted
      synergistically with LPS to increase plasma (400-fold) and liver (15-fold)
      concentrations of prostaglandin E(2) (PGE(2)) and significantly, but to a lesser
      extent, other PG compared with RA rats, in the absence of major differences in
      PLA(2) expression or activity or COX-1 and COX-2 mRNA or protein expression. The
      RA + LPS-mediated increase in PGE(2) was significantly attenuated (97%) by
      aminoguanidine (AG), a relatively specific inhibitor of the inducible nitric
      oxide synthase (NOS2), consistent with the previously reported synergistic effect
      of RA and LPS on NOS2 expression and activity. In addition, RA and LPS induced
      the expression of the microsomal isoform of PGE synthase (mPGES). In conclusion,
      in vivo, RA and LPS increased PG and especially PGE(2) concentrations. The PGE(2)
      increase was associated with NOS2-mediated activation of COX and induction of
      mPGES. These results contribute to the characterization of the effects of vitamin
      A on the host inflammatory response.

PMID- 11584083
TI  - Chronic docosahexaenoic acid intake enhances expression of the gene for
      uncoupling protein 3 and affects pleiotropic mRNA levels in skeletal muscle of
      aged C57BL/6NJcl mice.
AB  - Docosahexaenoic acid [DHA, 22:6(n-3)] prevents cardiovascular disease by
      decreasing obesity. It also prevents cancer and other geriatric diseases. We
      studied the chronic pleiotropic effects of DHA on transcription including that of
      mRNAs for uncoupling proteins (UCP). Male and female mice (9 mo old) were fed
      high (n-6) or high (n-3) fatty acid diets for 4 mo. Compared with controls fed
      high (n-6) fatty acid diets [high (n-6) group], the livers of male and female
      mice fed DHA [high (n-3) group] contained six- (P < 0.001) and fivefold (P <
      0.001) more DHA, respectively. The high (n-3) group had less white adipose tissue
      [35.3% in males (P < 0.001) and 27.3% in females (P < 0.001)]. The high (n-3)
      group expressed more uncoupling protein 3 (UCP3) in the gastrocnemius, 108%
      higher (P < 0.001) and 104% higher (P < 0.001) in males and females,
      respectively, than those in the high (n-6) group. However, the prevention of many
      diseases by DHA is not explained by UCP3. Thus, the gene expression profiles of
      both high (n-3) and high (n-6) groups were analyzed in skeletal muscle using cDNA
      expression array. Of 588 genes surveyed in the array, the high (n-3) group showed
      12 genes (2%) including those for glucose regulators (e.g., CD38) and tumor
      suppressors (e.g., CTCF) that were expressed 100-340% more than those of the high
      (n-6) group. Furthermore, 28 genes (4.8%), including growth factors (e.g., ErbB-2
      receptor) and immune regulators (e.g., interleukin-1 beta precursor) were
      expressed 50-90% less in the high (n-3) group than in the high (n-6) group. These
      results explain in part the important pleiotropic effects of DHA, which are
      independent of obesity control by UCP3 suppression.

PMID- 11584084
TI  - Polymorphisms of key enzymes in homocysteine metabolism affect diet
      responsiveness of plasma homocysteine in healthy women.
AB  - High plasma total homocysteine (tHcy), low dietary intake of folate and other B
      vitamins, and genetic polymorphisms related to metabolism of homocysteine may
      interactively contribute to the risk of cardiovascular disease. We investigated
      whether known mutations in genes regulating homocysteine metabolism affect the
      responsiveness of serum folate and plasma tHcy to high intake of natural folate
      from food. Healthy females (n = 37) aged 22-57 y volunteered to participate in a
      crossover dietary intervention with two 5-wk diet periods (low and high folate
      diets). Concentrations of serum and RBC folate, serum vitamin B-12 and plasma
      tHcy were measured at baseline and at the end of each diet period. The
      prevalences of C677T transition of methylenetetrahydrofolate reductase (MTHFR)
      gene, 844ins68 of cystathionine beta-synthase (CBS) gene and A2756G mutation of
      methionine synthase (MS) gene were determined. Compared with the low folate diet,
      the high folate diet increased the serum folate concentration by 85% (P < 0.001),
      77% (P < 0.001) and 55% (P < 0.05) in the subjects with the genotypes C/C (n =
      19), C/T (n = 13) and T/T (n = 5), respectively, of the MTHFR gene. Also, the
      plasma tHcy of the subjects with the genotypes C/C, C/T and T/T was decreased by
      11% (P < 0.001), 15% (P < 0.01) and 18% (P < 0.05), respectively, during the high
      folate diet period. The subjects carrying the G2756 allele of the MS gene (n =
      15) had a more extensive reduction (P < 0.05) of plasma tHcy during the high
      folate diet period than the subjects with the genotype A/A (n = 22). The 844ins68
      of CBS gene did not affect plasma tHcy concentrations or diet responsiveness. In
      conclusion, diet responsiveness of plasma homocysteine may be genetically
      regulated.

PMID- 11584085
TI  - Carbon dioxide is the major metabolite of quercetin in humans.
AB  - A previous study in ileostomy patients indicated that dietary glucosides of the
      flavonoid quercetin are hydrolyzed efficiently in the intestinal lumen, followed
      by absorption of a large fraction of the quercetin aglycone. To determine the
      fate of quercetin, we administered 1.85 MBq (50 microCi) of (14)C-quercetin both
      orally (100 mg, 330 micromol) and intravenously (iv; 0.3 mg, 1 micromol) to
      healthy volunteers. Serial plasma samples, urines and stools were collected for
      72 h. Total radioactivity was determined by liquid scintillation spectrometry
      directly in plasma and urine and after repeated methanol extraction of stool
      homogenate samples. The oral absorption, based on total radioactivity, was
      surprisingly high, ranging from 36.4 to 53.0%. The biological half-life was very
      long, ranging from 20 to 72 h. The urinary recovery of total radioactivity ranged
      from 18.4 to 26.8% after the iv dose and from 3.3 to 5.7% after the oral dose.
      The corresponding fecal recoveries were only 1.5-5.0% and 1.6-4.6%, respectively.
      Thus, the total recovery of the (14)C-quercetin doses, in particular after oral
      administration, was very low. In search for the unaccounted for fraction of the
      (14)C-quercetin dose, we performed (14)CO(2) recovery studies in three volunteers
      (3 iv and 3 oral doses). At timed intervals, (14)CO(2) in expired air was trapped
      in hyamine hydroxide/thymolphthalein and analyzed for radioactivity. As much as
      23.0-81.1% of the quercetin dose was recovered as (14)CO(2) in the expired air
      from these volunteers, after both oral and iv doses. The disposition of quercetin
      in humans is thus highly complex, requiring further studies.

PMID- 11584086
TI  - Dietary methionine is involved in the etiology of neural tube defect-affected
      pregnancies in humans.
AB  - Research has provided evidence of the role of multivitamin supplementation in the
      prevention of neural tube defects (NTD). Failure of the neural tube to close is
      one of the most frequent and severe human developmental defects. The etiology of
      NTD is complex, encompassing genetic, dietary and environmental factors. The
      purpose of this study was to explore the relationship between maternal dietary
      intake of methionine and the risk of having a NTD-affected pregnancy. We
      hypothesized that women with high maternal dietary methionine intake were at a
      decreased risk for a NTD. Combinations of methionine, folate and vitamin B-12
      intakes and NTD risk were also examined. Data from a 5-y, population-based, case
      control study of 170 NTD-affected pregnancies and 269 controls were provided by
      the South Carolina NTD Surveillance, Prevention, and Research Project. There was
      a 30-55% lower NTD risk among women whose average daily dietary intake of
      methionine was greater than the lowest quartile of intake (>1580 mg/d). The odds
      ratios associated with the three quartiles of methionine intake > 1580 mg/d after
      adjusting for energy, race and body mass index were 0.72 (P < 0.07), 0.68 (P <
      0.07) and 0.45 (P < 0.06), respectively. These findings indicate that a reduction
      in the risk of having a NTD-affected pregnancy is associated with maternal
      dietary intake of methionine (3 mo pre- to 3 mo postconception). This finding is
      consistent with the hypothesis that methionine plays a role in the etiology of
      NTD and suggests the need for further research in the area of maternal diet and
      pregnancy.

PMID- 11584087
TI  - Exercise affects protein utilization in healthy children.
AB  - Although health initiatives promote increased physical activity in children, the
      physiologic outcomes have not been well characterized. This investigation
      examined the effects of programmed aerobic exercise on protein metabolism in
      children (n = 7; mean +/- SEM: 9.14 +/- 0.46 y old; weight, 32.1 +/- 1.6 kg;
      height, 138 +/- 2.5 cm; and body mass index, 16.21 +/- 0.36 kg/m(2) ) using (15)N
      glycine methodology. Boys (n = 5) and girls (n = 2) walked (5 d/wk, 3.2-6.4 km/d)
      for 6 wk. Criterion measures taken at baseline (Pre) and after the exercise
      program (Post) included anthropometric data, dietary assessment, nitrogen
      balance, nitrogen flux (Q), protein synthesis (PS), protein breakdown (PB) and
      net protein balance [(Net) = PS - PB]. After the walking program, there were no
      significant changes in body weight, fat-free mass or percentage of body fat,
      whereas height increased (P < 0.01). Energy and protein intakes were constant
      throughout the study. Nitrogen balance was significantly more positive Post than
      Pre (P < 0.05). There was a significant decrease in Q (P < 0.0001) with
      corresponding decreases in PS (P < 0.001) and PB (P < 0.01). These data provide
      the first evidence that programmed aerobic exercise alters whole-body protein
      utilization in healthy, nonobese children. Longitudinal studies are required to
      further examine changes in protein metabolism associated with increased physical
      activity in this population. In addition, findings suggest a need to evaluate
      nutrient requirements for healthy, physically active boys and girls.

PMID- 11584088
TI  - Weekly vitamin A and iron supplementation during pregnancy increases vitamin A
      concentration of breast milk but not iron status in Indonesian lactating women.
AB  - Studies on the effect of vitamin A and iron supplementation during pregnancy on
      maternal iron and vitamin A status postpartum are scarce. We investigated whether
      retinol and iron variables in breast milk and in serum postpartum were enhanced
      more with weekly vitamin A and iron supplementation during pregnancy than with
      weekly iron supplementation. During pregnancy, subjects were randomly allocated
      to two groups and received either (n = 88) a weekly supplement of iron (120 mg Fe
      as FeSO(4)) and folic acid (500 microg) or (n = 82) the same amount of iron and
      folic acid plus vitamin A [4800 retinol equivalents (RE)]. Transitional milk (4-7
      d postpartum) had higher (P < 0.001) concentrations of retinol and iron than
      mature milk (3 mo postpartum). Compared with the weekly iron group, the weekly
      vitamin A and iron group had a greater (P < 0.05) concentration of retinol in
      transitional milk (as micromol/L) and in mature milk (as micromol/g fat).
      Although serum retinol concentrations approximately 4 mo postpartum did not
      differ significantly, the weekly vitamin A and iron group had significantly fewer
      (P < 0.01) subjects with serum retinol concentrations < or = 0.70 micromol/L than
      the weekly iron group. Iron status and concentrations of iron in transitional and
      mature milk did not differ between groups. We have shown that weekly vitamin A
      and iron supplementation during pregnancy enhanced concentrations of retinol in
      breast milk although not in serum by approximately 4 mo postpartum. However, no
      positive effects were observed on iron status and iron concentration in breast
      milk.

PMID- 11584089
TI  - Household food insecurity with hunger is associated with women's food intakes,
      health and household circumstances.
AB  - This study investigated food intake patterns and contextual factors related to
      household food insecurity with hunger among a sample of 153 women in families
      seeking charitable food assistance in Toronto. Women in households characterized
      by food insecurity with severe or moderate hunger over the past 30 d (as assessed
      by the Food Security Module) reported lower intakes of vegetables and fruit, and
      meat and alternatives than those in households with no hunger evident. Women were
      more likely to report household food insecurity with hunger over the past 12 mo
      and 30 d if they also reported longstanding health problems or activity
      limitations, or if they were socially isolated. The circumstances that women
      identified as precipitating acute food shortages in their households included
      chronically inadequate incomes; the need to meet additional, unusual
      expenditures; and the need to pay for other services or accumulated debts. Women
      who reported delaying payments of bills, giving up services, selling or pawning
      possessions, or sending children elsewhere for a meal when threatened with acute
      food shortages were more likely to report household food insecurity with hunger.
      These findings suggest that expenditures on other goods and services were
      sometimes foregone to free up money for food, but the reverse was also true.
      Household food insecurity appears inextricably linked to financial insecurity.

PMID- 11584090
TI  - Selenium and zinc status are suboptimal in a sample of older New Zealand women in
      a community-based study.
AB  - The importance of selenium and zinc in the immune functioning of the aged is
      widely recognized. Seniors in New Zealand are at particularly high risk of low
      selenium status because of the low selenium soil environment. The zinc status of
      the New Zealand elderly has never been assessed. In this cross-sectional study,
      the biochemical selenium, zinc and lipid levels, physical functional capacity and
      dietary intakes of 103 randomly selected free-living New Zealand women (mean age
      +/- SD, 75 +/- 3 y) were assessed. Among nonusers of selenium supplements (n =
      80), 80% [95% confidence interval (CI): 70; 88%] had plasma selenium levels (0.85
      +/- 0.23 micromol/L) below 1.00 micromol/L [ approximately 10% below mean plasma
      selenium necessary for full expression of glutathione peroxidase (GPx) activity
      in New Zealand subjects]. Plasma selenium was strongly correlated with GPx: r =
      0.56; P < 0.0001. For nonusers of zinc supplements (n = 88), serum zinc
      concentrations were 12.4 +/- 1.4 micromol/L, with 12% (95% CI: 6; 21%) having
      levels below the cut-off value (10.7 micromol/L). Estimated mean daily selenium
      and zinc intakes were 34 +/- 10 microg and 8.7 +/- 2.0 mg, respectively. Subjects
      in the highest tertile of a functional capacity index had higher biochemical zinc
      and selenium values than those in the lowest tertile (P < 0.05). The correlation
      between plasma selenium and GPx indicates that selenium intake in these women is
      still insufficient for full expression of GPx activity. Lower serum zinc levels
      also appear to be prevalent. Because a suboptimal trace element status may be
      more common among those with a poor physical functioning, promotion of the
      consumption of nutrient dense foods or supplements to improve selenium and zinc
      status of elderly women in New Zealand may be beneficial.

PMID- 11584091
TI  - Household food insecurity was prevalent in Java during Indonesia's economic
      crisis.
AB  - Valid assessment of household food security is important, particularly in rapidly
      changing circumstances such as the economic crisis that struck Indonesia in 1998.
      The Cornell-Radimer tool for measuring household food security has now been used
      in several social and economic settings. An adaptation of this tool was used in
      the context of the economic crisis of Java, Indonesia in June-August 1998 in a
      survey of 1423 mothers with children < 5 y old. Qualitative and quantitative data
      contributed to understanding food insecurity and provided evidence for some
      aspects of validity. The data showed substantial household food insecurity with
      94.2% of households found to be uncertain or insecure about their food situation
      in the previous year. Of respondents, 11% reported losing weight in the previous
      year because of lack of food. Food security in Java was undoubtedly compromised
      by the economic crisis. These results suggest, on the basis of qualitative and
      quantitative understandings of food insecurity, that this tool provided a useful
      measure of the situation in Java in 1998. From this study and others done
      recently, such a tool or ones constructed using a similar approach have been
      found to be useful in various settings in which there is a need to understand and
      identify household food insecurity for purposes of estimating and monitoring
      prevalence and targeting of policies and programs. Further research to validate
      this approach in various settings is warranted.

PMID- 11584092
TI  - The nutrition transition is underway in India.
AB  - Nutrition research in India has previously focused on the serious problem of
      undernutrition related to nutrient deficit and high rates of infection. Recent
      data from the National Family Health Survey 1998/99 (NFHS 2), however, identified
      a significant proportion of Indian women as overweight, coexisting with high
      rates of malnutrition. This paper examines the emerging nutrition transition for
      women living in rural and urban communities of Andhra Pradesh, India. NFHS 2
      provides nationally representative data on women's weight and height. In this
      paper, we examine representative data from the state of Andhra Pradesh (n = 4032
      women). Logistic regression analyses are applied to the data to identify
      socioeconomic, regional and demographic determinants of overweight and thinness.
      The major nutrition problem facing women continues to be undernutrition, with 37%
      having a low body mass index [(BMI) < 18.5 kg/m(2)]; 8% of these women are
      severely malnourished (BMI < 16 kg/m(2)). However, 12% of the women can be
      classified as overweight (BMI > 25 kg/m(2)) and 2% are obese (BMI > 30 kg/m(2)).
      Furthermore, in the large cities of the state in which 4% of the sample live, 37%
      of women are overweight or obese, whereas in the rural areas in which 74% reside,
      43% have a low BMI. Women from lower socioeconomic groups are also significantly
      more likely to have a low BMI. Findings from the logistic regression models
      reveal socioeconomic status to be a more important predictor of both over- and
      underweight than location of residence.

PMID- 11584093
TI  - Serum thyroglobulin and urinary iodine concentration are the most appropriate
      indicators of iodine status and thyroid function under conditions of increasing
      iodine supply in schoolchildren in Benin.
AB  - Iodine deficiency control programs have greatly reduced iodine deficiency
      disorders worldwide. For monitoring changes in iodine status, different
      indicators may be used. The aim of this study was to evaluate the suitability of
      indicators of iodine status and thyroid function, thyroglobulin (Tg), thyroid
      stimulating hormone (TSH) and free thyroxine (FT4) in serum, thyroid volume and
      urinary iodine concentration, in iodine-deficient schoolchildren under conditions
      of increasing iodine supply. The study was established as a double-blind, placebo
      controlled oral administration of a single dose of iodized oil to schoolchildren
      (7-10 y old), living in an iodine-deficient area of Benin, with an observation
      period of 10 mo. However, 3-4 mo after supplementation, iodized salt became
      available in the area. The study population therefore comprised an iodized oil
      supplemented group and a nonsupplemented group, both of which had variable,
      uncontrolled intakes of iodized salt during the last 6 mo of the study. Initial
      mean serum concentrations of TSH and FT4 were within the normal range, whereas
      serum Tg concentration, urinary iodine concentration and thyroid volume were
      indicative of moderate-to-severe iodine deficiency. At the end of the study, all
      indicators had improved significantly, except thyroid volume, which had decreased
      only in the supplemented group. The supplemented group also still had
      significantly lower serum Tg and higher urinary iodine concentrations than the
      nonsupplemented group. Serum Tg and urinary iodine concentrations are the
      indicators most influenced by a changing iodine supply. Current normal reference
      ranges of serum concentrations of TSH and FT4 are too wide for detecting iodine
      deficiency in this age group.

PMID- 11584094
TI  - Comparison of infant feeding patterns reported for nonindustrial populations with
      current recommendations.
AB  - The observation that young child-feeding practices rarely conform to current
      global recommendations is of major public health nutrition policy concern and
      raises questions about whether near-universal compliance with recommendations is
      feasible in any population. This analysis uses indicators of age at introduction
      of complementary foods and termination of breastfeeding available from
      ethnographic and demographic reports published between 1873 and 1998 to test the
      hypothesis that recent and contemporary nonindustrial societies practice patterns
      of infant feeding concordant with current global recommendations. Results suggest
      that ethnographically reported average ages at introduction of nonbreast milk
      liquids (4.5 +/- 6.0 mo) and solids (5.0 +/- 4.0 mo) and the duration of
      breastfeeding (29.0 +/- 10.0 mo) among a sample of 113 such populations concord
      with those at which key weaning transitions are biologically optimal for most
      normal healthy children. However, wide variation in estimates across populations
      remains unexplained and serious limitations in the available data preclude proper
      assessment of the underlying distribution of the timing of weaning transitions
      within populations.

PMID- 11584095
TI  - Heat moisture treatment of high amylose cornstarch increases its resistant starch
      content but not its physiologic effects in rats.
AB  - To examine whether the physiologic effects of high amylose cornstarch (HACS) are
      affected by gelatinization or heat moisture treatment, male rats were fed for 21
      d a fiber-free purified diet containing 40 g/100 g gelatinized normal cornstarch
      (G-CS), HACS, gelatinized high amylose cornstarch (G-HACS) or heat moisture
      treated HACS (HMCS). Dietary fiber (DF) content in G-HACS was 87% lower than that
      in HACS. The apparent starch and protein digestibilities were higher in the G
      HACS group than in the HACS group. Fecal wet weight and fecal bile acid excretion
      were lower in the G-HACS group than in the HACS group. The cecal tissue weight,
      cecal surface area, cecal content weight and cecal pH were lower in the G-HACS
      group than in the HACS group. The cecal n-butyric acid and succinic acid
      concentrations were higher and lower, respectively, in the G-HACS group than in
      the HACS group. The plasma cholesterol and triacylglycerol concentrations did not
      differ between the G-HACS group and the HACS group. On the other hand, the DF
      content in HMCS was 330% higher than that in HACS, but the HMCS and HACS groups
      generally did not differ except in cecal surface area. Dietary starch did not
      affect fecal moisture, fecal neutral sterol (cholesterol + coprostanol)
      excretion, liver cholesterol level, total short-chain fatty acid (SCFA)
      concentration or apparent Ca, Fe, Mg and Zn absorptions. These results show that
      the heat moisture treatment of HACS for the most part does not alter its
      physiologic effects despite the greater DF content.

PMID- 11584096
TI  - Pre- and postnatal dietary conjugated linoleic acid alters adipose development,
      body weight gain and body composition in Sprague-Dawley rats.
AB  - Sprague-Dawley rats were fed either a control diet (7 g/100 g soybean oil) or a
      conjugated linoleic acid (CLA) diet (6.5 g/100 g soybean oil and 0.5 g/100 g CLA)
      beginning on d 7 of gestation to determine whether pre- and postnatal CLA affects
      short- and long-term growth and adiposity. At weaning (d 21), progeny were
      assigned control or CLA diet and fed until 11 wk of age. At birth, litter size
      and weight were not different between treatments. There were age- and sex
      dependent changes in inguinal adipose fatty acid composition at birth and
      weaning, whereas there were no differences in lipid accretion or adipocyte
      proliferation. At weaning, CLA did not alter inguinal adipocyte proliferation but
      increased (P < 0.01) CCAAT/enhancer binding protein alpha expression in inguinal
      adipose tissue from females, whereas there was no difference in expression in
      males. Significant differences in size distribution of inguinal adipocytes at
      weaning and retroperitoneal adipocytes at 11 wk of age were observed. In general,
      CLA increased the proportion of smaller cells and decreased the proportion of
      larger cells. The main long-term effect of the dams' diet was the significantly
      heavier gastrocnemius and soleus muscles, and significantly longer tail lengths,
      an indication of skeletal growth, of male pups whose dams were fed CLA.
      Postweaning diet reduced fat pad weights in female but not male pups fed CLA.
      This response was due to differences in cell size rather than number. Response to
      CLA treatment may depend on the sex and age of the animal as well as duration of
      feeding.

PMID- 11584097
TI  - Overexpression of arginase alters circulating and tissue amino acids and
      guanidino compounds and affects neuromotor behavior in mice.
AB  - Arginine is an intermediate of the ornithine cycle and serves as a precursor for
      the synthesis of nitric oxide, creatine, agmatine and proteins. It is considered
      to be a conditionally essential amino acid because endogenous synthesis only
      barely meets daily requirements. In rapidly growing suckling neonates, endogenous
      arginine biosynthesis is crucial to compensate for the insufficient supply of
      arginine via the milk. Evidence is accumulating that the intestine rather than
      the kidney plays a major role in arginine synthesis in this period. Accordingly,
      ectopic expression of hepatic arginase in murine enterocytes by genetic
      modification induces a selective arginine deficiency. The ensuing phenotype,
      whose severity correlates with the level of transgene expression in the
      enterocytes, could be reversed with arginine supplementation. We analyzed the
      effect of arginine deficiency on guanidine metabolism and neuromotor behavior.
      Arginine-deficient transgenic mice continued to suffer from an arginine
      deficiency after the arginine biosynthetic enzymes had disappeared from the
      enterocytes. Postweaning catch-up growth in arginine-deficient mice was
      characterized by increased levels of all measured amino acids except arginine.
      Furthermore, plasma total amino acid concentration, including arginine, was
      significantly lower in adult male than in adult female transgenic mice. Decreases
      in the concentration of plasma and tissue arginine led to significant decreases
      in most metabolites of arginine. However, the accumulation of the toxic guanidino
      compounds, guanidinosuccinic acid and methylguanidine, corresponded inversely
      with circulating arginine concentration, possibly reflecting a higher oxidative
      stress under hypoargininemic conditions. In addition, hypoargininemia was
      associated with disturbed neuromotor behavior, although brain levels of toxic
      guanidino compounds and ammonia were normal.

PMID- 11584098
TI  - Validity and reproducibility of a self-administered food-frequency questionnaire
      to assess isoflavone intake in a japanese population in comparison with dietary
      records and blood and urine isoflavones.
AB  - Valid food-frequency questionnaires (FFQ) need to be developed to assess
      isoflavone intake in investigations of its possible association with the lower
      incidence of breast and prostate cancer in Asian countries. We investigated the
      validity and reproducibility of isoflavone (daidzein and genistein) intakes from
      self-administered semiquantitative FFQ used in the JPHC Study (Japan Public
      Health Center-based Prospective Study on Cancer and Cardiovascular Diseases). We
      also investigated the number of food items that would be sufficient to ensure
      validity and reproducibility. We collected FFQ, dietary records (DR), blood and
      urine samples from 215 subjects among JPHC Study participants, estimated
      isoflavone intakes from FFQ and DR, and measured serum isoflavone concentration
      and urine isoflavone excretion. For daidzein, mean intakes estimated from FFQ and
      DR, serum concentration and urine excretion were 18.3 mg/d, 14.5 mg/d, 119.9
      nmol/L and 17.0 micromol/d and for genistein, 31.4 mg/d, 23.4 mg/d, 475.3 nmol/L
      and 14.2 micromol/d, respectively. Results were similar when analyzed by sex.
      Spearman correlation coefficients for daidzein of energy-adjusted intakes from
      FFQ with those from DR, serum concentration and creatinine-adjusted urinary
      excretion were 0.64, 0.31 and 0.43, respectively. Correlations between two FFQ
      estimates with a 1-y interval were 0.76. Results were similar for genistein. The
      shorter version of the FFQ with three items (natto, miso and tofu for miso soup)
      showed a similar correlation. The original FFQ and the shorter versions have
      sufficient validity and reproducibility to be used in epidemiologic studies.

PMID- 11584099
TI  - A cross-sectional study of human serum sphingolipids, diet and physiologic
      parameters.
AB  - Sphinganine and sphingosine, the two sphingoid base backbones of sphingolipids,
      are highly bioactive compounds that are of increasing interest to nutritionists
      because they occur in food and their metabolism can be altered by fungal toxins
      that contaminate some foods. Nonetheless, no studies of diet and sphinganine or
      sphingosine concentrations in serum have yet been reported. Here we describe a
      cross-sectional study of 265 residents of Linxian, People's Republic of China,
      which examines potential demographic, physiologic and dietary correlates of serum
      sphinganine and sphingosine in this population. Median concentrations of serum
      sphinganine and sphingosine were compared among strata for 29 different
      variables. For sphinganine, no significant differences were found. For
      sphingosine, significant differences were seen among strata of age, menstruation
      status, serum cholesterol, carotenoids, retinol, tocopherols, fresh and dried
      vegetable and fresh fruit consumption. Using multivariate linear regression with
      stepwise selection, we found that the significant predictors for serum
      sphingosine included total tocopherols, age, serum selenium and retinol, with a
      final R(2) = 0.22; for sphinganine, tooth loss was the sole correlate, with R(2)
      = 0.015. Analyses using ranked sphingolipid data or principal components
      analysis, to simplify the food variables, did not materially alter these results.
      This study represents the largest report of human serum sphingolipid
      concentrations to date and provides insight into potential explanatory variables
      that can be incorporated into future studies.

PMID- 11584100
TI  - Life span is prolonged in food-restricted autoimmune-prone (NZB x NZW)F(1) mice
      fed a diet enriched with (n-3) fatty acids.
AB  - Moderate food and/or energy (calorie) restriction delays age-related immune
      dysfunction and prolongs life span in multiple animal models. The amount and type
      of dietary fatty acids can also profoundly affect life span. Marine-derived fish
      oils contain (n-3) fatty acids, which have potent anti-inflammatory properties.
      We therefore examined the influence of food restriction (40% overall reduction in
      intake of all dietary components) combined with substitution of fish oil for corn
      oil in a factorial design. Autoimmune-prone (NZB x NZW)F(1) (B/W) mice, which
      develop fatal autoimmune renal disease, were used. The food-restricted/fish oil
      diet maximally extended median life span to 645 d (vs. 494 d for the food
      restricted corn oil diet). Similarly, fish oil prolonged life span in the ad
      libitum-fed mice to 345 d (vs. 242 for the ad libitum/corn oil diet). Increased
      life span was partially associated with decreased body weight, blunting renal
      proinflammatory cytokine (interferon-gamma, interleukins-10 and -12 and tumor
      necrosis factor-alpha) levels and lower nuclear factor-kappaB (NF-kappaB).
      Reductions in NF-kappaB were preceded by enhanced superoxide dismutase, catalase
      and glutathione peroxidase activities. These findings demonstrate the profound
      additive effects of food restriction and (n-3) fatty acids in prolonging life
      span in B/W mice. These observations may have additional implications in the
      management of obesity, diabetes, cancer and/or the aging process.

PMID- 11584102
TI  - Carbohydrate: friend or foe? Summary of research needs.
AB  - This symposium evaluated the current state of science relative to the role of
      carbohydrates in human health and identified priority research topics to address
      gaps in our knowledge about carbohydrates and health. Future revisions of dietary
      guidelines will benefit from an expanded research agenda leading to a better
      understanding of the benefits and risks of consuming diets high in carbohydrates.

PMID- 11584103
TI  - Choose beverages and foods to moderate your intake of sugars: the 2000 dietary
      guidelines for Americans--what's all the fuss about?
AB  - As part of the 2000 Dietary Guidelines for Americans, the public is advised to
      choose beverages and foods to moderate their intake of sugars. The term sugars is
      conventionally used to describe the mono- and disaccharides. However, the Dietary
      Guidelines for Americans distinguish between added sugars and other sources of
      carbohydrates. The concept of added sugars provides consumers with useful
      information, especially if they are trying to limit excessive use of caloric
      sweeteners. Added sugars are defined as sugars that are eaten separately at the
      table or used as ingredients in processed or prepared foods. Consumption of added
      sugars has increased steadily as documented by both food supply data and
      nationwide food consumption survey data. The largest source of added sugars in
      the U.S. diet is nondiet soft drinks, accounting for one third of total intake.
      Diets high in sugars have been associated with various health problems, including
      dental caries, dyslipidemias, obesity, bone loss and fractures, and poor diet
      quality. Research gaps are identified.

PMID- 11584104
TI  - Effect of dietary carbohydrate on triglyceride metabolism in humans.
AB  - When the content of dietary carbohydrate is elevated above the level typically
      consumed (>55% of energy), blood concentrations of triglycerides rise. This
      phenomenon, known as carbohydrate-induced hypertriglyceridemia, is paradoxical
      because the increase in dietary carbohydrate usually comes at the expense of
      dietary fat. Thus, when the content of the carbohydrate in the diet is increased,
      fat in the diet is reduced, but the content of fat (triglycerides) in the blood
      rises. The present article will review studies of carbohydrate-induced
      hypertriglyceridemia, highlighting data obtained in fasted subjects habituated to
      high carbohydrate diets, data obtained from subjects in the fed state, and
      metabolic studies investigating fatty acid and triglyceride synthesis in subjects
      consuming diets of different carbohydrate content. The available data have been
      recently expanded by new methodologies, such as the use of stable isotopes, to
      investigate the metabolism of sugars in humans in vivo. Given the significant
      increase in body weight observed in the American population over the past decade
      and the changing availability of carbohydrate in the food supply, future studies
      of carbohydrate-induced hypertriglyceridemia promise to provide important
      information of how the macronutrient composition of the diet can influence
      health.

PMID- 11584105
TI  - Carbohydrates, appetite and feeding behavior in humans.
AB  - The view of carbohydrates in relation to obesity has changed over the past few
      decades from being conducive to overconsumption and weight gain to being
      protective. This article reviews the mechanisms by which carbohydrate is
      purported to protect against weight gain. Although carbohydrate is metabolized
      and stored in the body less efficiently than fat, when de novo lipogenesis is
      invoked on very high carbohydrate diets, the beneficial effect on energy balance
      is likely to be minimal when typical high fat Western diets are consumed.
      However, it has been suggested that high carbohydrate foods may influence energy
      balance by reducing food intake through greater satiety effects, reducing energy
      density and displacing fat from the diet-the fat-sugar seesaw effect. To date,
      there seem to be few differences between sugars and starches on satiety and
      energy intake, but few studies have examined this. Some reduced-fat, and,
      therefore, higher carbohydrate, foods are highly energy dense. High carbohydrate
      foods do not necessarily have a low energy density. Evidence from recent studies
      suggests that adding carbohydrate, and especially sugar, to the diet neither
      displaces fat from the diet nor protects against elevated energy intake. Although
      it is easier to overeat on high fat than low fat foods, simply replacing fat with
      carbohydrate in the diet may not be as protective against overconsumption as the
      energy density or fat-sugar seesaw arguments suggest.

PMID- 11584106
TI  - The role of carbohydrates in insulin resistance.
AB  - Insulin resistance is a metabolic disorder that is increasing worldwide and is
      associated with some of the most common diseases affecting modern societies
      including diabetes, hypertension, obesity and coronary heart disease. Although
      pharmacologic approaches to managing insulin resistance are being advocated by
      some, public health approaches involving changes in diet and physical activity
      are attractive because of their lower cost and risk. We briefly summarize some
      new information on the mechanisms that mediate insulin's many biological actions
      and examine the effects of dietary carbohydrates on insulin sensitivity.
      Specifically, we summarize some of the information available on the effects of
      simple sugars, complex carbohydrates including fiber, slowly digested starch and
      the general concept of glycemic index. The available data support the idea that
      consumption of diets high in total carbohydrate does not adversely affect insulin
      sensitivity compared with high fat diets. Animal data suggest that simple sugars,
      in particular fructose, have adverse effects on insulin action, but adverse
      effects have not been shown conclusively in humans. Increased intake of dietary
      fiber appears to improve insulin action and may protect against the development
      of diabetes. The effects of diets with high or low glycemic index on insulin
      action are controversial at this time. For firm conclusions to be reached, future
      studies must be of reasonable duration, be in defined populations and compare the
      effects of relevant doses of nutrients on specific endpoints of insulin action.

PMID- 11584107
TI  - Chronic nutritional diseases of infectious origin: an assessment of a nascent
      field.

PMID- 11584108
TI  - Helicobacter pylori: ulcers and more: the beginning of an era.
AB  - Helicobacter pylori (H. pylori) may be found in up to 50% of the world's
      population, making it the most common infectious disease worldwide. H. pylori is
      a gram-negative, microaerophilic rod with flagella and normally resides in the
      stomach. It can be diagnosed endoscopically, via breath tests, or through a
      simple blood test. H. pylori can usually be eradicated with a combination of
      proton pump inhibitors and antibiotics. Although most people infected with this
      organism never develop a complication, H. pylori infection in others may produce
      significant mucosal inflammation leading to ulcers in the stomach and duodenum.
      H. pylori has also been recognized as a risk factor for the development of both
      gastric carcinoma and mucosal-associated lymphoid tumor. Although not widely
      known, H. pylori can also affect organ systems outside of the gastrointestinal
      tract. It is now apparent that H. pylori can infect the skin, liver and heart and
      that these infections may produce a number of different disease states. In
      addition, H. pylori infection can adversely affect the nutritional status of both
      children and adults. This article discusses the epidemiology and bacteriology of
      H. pylori, reviews the different methods of diagnosing and treating this common
      infection, and then focuses on the effects that H. pylori has on different organ
      systems within the body, including the nutritional status of those affected.

PMID- 11584109
TI  - Infectobesity: obesity of infectious origin.
AB  - In the U.S., the prevalence of obesity increased by 30% from 1980 to 1990, and
      this increase appears to be continuing. Although obesity has multiple etiologies,
      an overlooked possibility is obesity of an infectious origin. Six pathogens are
      reported to cause obesity in animals. Canine distemper virus was the first virus
      reported to cause obesity in mice, followed by Rous-associated virus-7, an avian
      retrovirus, which has been shown to cause stunting, obesity and hyperlipidemia in
      chickens. Next, the obesity-promoting effect of Borna disease virus was
      demonstrated in rats. Scrapie agents were reported to induce obesity in mice and
      hamsters. The final two reports were of SMAM-1, an avian adenovirus, and Ad-36, a
      human adenovirus that caused obesity in animals. Additionally, an association
      with human obesity is the unique feature of SMAM-1 and Ad-36. Although the exact
      mechanism of pathogen-induced obesity is unclear, infection attributable to
      certain organisms should be included in the long list of potential etiological
      factors for obesity. In addition, the involvement of some pathogens in etiology
      of obesity suggests the possibility of a similar role for additional pathogens.

PMID- 11584110
TI  - Do pathogens accelerate atherosclerosis?
AB  - Infection with the pathogens human cytomegalovirus (HCMV) or Chlamydia pneumonia
      (CP) is linked to the development of vascular disease, including atherosclerosis.
      The role of pathogens in vasculopathies has been controversial. However, animal
      models have demonstrated a direct link between infection with CP and
      herpesviruses and the development of vascular disease. Clinical studies have
      shown a direct association of HCMV and CP with the acceleration of vascular
      disease. This article will review the evidence supporting the role for CP and
      HCMV in the development of vascular disease and will suggest a potential
      mechanism for HCMV acceleration of the disease process. Vascular diseases are the
      result of either mechanical or immune-related injury followed by inflammation and
      subsequent smooth muscle cell (SMC) proliferation and/or migration from the
      vessel media to the intima, which culminates in vessel narrowing. A number of in
      vitro and in vivo models have provided potential mechanisms involved in pathogen
      mediated vascular disease. Recently, we have demonstrated that HCMV infection of
      arterial but not venous SMC results in significant cellular migration in vitro.
      Migration was dependent on expression of the HCMV-encoded chemokine receptors,
      US28, and the presence of the chemokines, RANTES or MCP-1. Migration involved
      chemotaxis and provided the first evidence that viruses may induce migration of
      SMC toward sites of chemokine production through the expression of a virally
      encoded chemokine receptor in infected SMC. Because SMC migration into the
      neointimal space is the hallmark of vascular disease, these observations provide
      a molecular link between HCMV and the development of vascular disease.

PMID- 11584111
TI  - Viral induction of type 2 diabetes and autoimmune liver disease.
AB  - Cross-sectional studies performed worldwide have shown that hepatitis C virus
      (HCV) infection is linked with type 2 diabetes, but these endocrine and liver
      diseases have an insidious onset, and it has been difficult to establish that
      patients acquire HCV infection before the development of diabetes. It is likely
      that investigations in small animal models or in vitro systems will be required
      to determine whether a causal relationship of HCV infection and the development
      of diabetes can be established. We have developed an in vitro model to study the
      viral induction of primary biliary cirrhosis (PBC) based on the phenotype of the
      diseased biliary epithelial cells. PBC patients make antimitochondrial antibodies
      and also express proteins reactive to these antibodies on their biliary
      epithelium. In coculture studies we have found that normal biliary epithelial
      cells develop the phenotypic manifestation of PBC in vitro specifically when
      cultivated with lymph nodes from PBC patients and not with relevant liver disease
      control subjects. We have also cloned a novel human retrovirus from a PBC biliary
      epithelium cDNA library and confirmed that the development of the PBC phenotype
      in vitro coincides with the presence of this virus. In clinical trials using
      antiretroviral therapy, we have observed a reversal of ductopenia as well as
      improvements in histology and hepatic biochemistry in patients with PBC. As
      Koch's postulates are not readily applicable to chronic diseases, we have used
      cocultivation viral transmission model in vitro and antimicrobial clinical
      studies in vivo to help establish a causal relationship with a retrovirus
      infection and the phenotypic manifestation of disease.

PMID- 11584112
TI  - The pathogens are speaking: are we listening?

PMID- 11584113
TI  - Use of keyboards as an occupational hazard.

PMID- 11584114
TI  - Respiratory illnesses and ventilatory function among workers at a cement factory
      in a rapidly developing country.
AB  - Chronic exposure to Portland cement dust has been reported to lead to a greater
      prevalence of chronic respiratory symptoms and a reduction of ventilatory
      capacity. The seriousness of pulmonary function impairment and respiratory
      disease has not been consistently associated with the degree of exposure. Regular
      use of appropriate personal protective equipment, if available at the worksite,
      could protect cement workers from adverse respiratory health effects. For a
      variety of reasons, industrial workers in rapidly developing countries do not
      adequately protect themselves through personal protective equipment. This study
      explores the prevalence of chronic respiratory symptoms and ventilatory function
      among cement workers and the practice of use of personal protective equipment at
      work. An interviewer-administered questionnaire was used to collect information
      on sociodemographic characteristics, smoking profile and history of respiratory
      health among workers at a Portland cement plant (exposed) and workers
      occupationally unexposed to dust, fumes and gases (unexposed). Pulmonary function
      was assessed and pulmonary function impairment was calculated for the exposed and
      the unexposed workers. A higher percentage of the exposed workers reported
      recurrent and prolonged cough (30%), phlegm (25%), wheeze (8%), dyspnoea (21%),
      bronchitis (13%), sinusitis (27%), shortness of breath (8%) and bronchial asthma
      (6%). Among the unexposed, prevalences of these symptoms were 10, 5, 3, 5, 4, 11,
      4 and 3%, respectively. Ventilatory function (VC, FVC, FEV(1), FEV(1)/VC,
      FEV(1)/FVC and PEF) was significantly lower in the exposed workers compared with
      unexposed workers. These differences could not be explained by age, body mass
      index (BMI) or pack-years smoked. Ventilatory function impairment, as measured by
      FEV(1)/FVC, showed that 36% of the exposed workers had some ventilatory function
      impairment compared with 10% of those unexposed. Certain jobs with greater
      exposure to cement dust had lower ventilatory function compared with others among
      the exposed workers. It was concluded that adverse respiratory health effects
      (increased frequency of respiratory symptoms and decreased ventilatory function)
      observed among cement workers could not be explained by age, BMI and smoking, and
      were probably caused by exposure to cement dust.

PMID- 11584115
TI  - Biological monitoring of workers exposed to dimethylformamide in a textile
      polyurethane unit.
AB  - Dimethylformamide (DMF) is a universal solvent noted for its solubility in both
      aqueous and lipid media. It is hepatotoxic, and there are concerns about its
      carcinogenicity. Our objective was to determine the correlation between air
      monitoring measurements and biological measurements of a suitable metabolite of
      DMF in a cohort of operatives in a polyurethane production unit. This was done
      with a view to assessing how much the inhalation route contributed to total DMF
      exposure, mainly for control purposes. We investigated the relationship between
      personal air sample measurements of DMF and biological measurements of N
      methylformamide (NMF) in nine adult subjects, recruited across the shifts, with
      varying levels of exposure to DMF. Personal exposure monitoring was carried out
      with a low-flow-rate Model 222-4 SKC pump, while post-shift urine samples were
      obtained for further analysis. Operatives were asked to abstain from consuming
      alcohol for 24 h before the designated shift, as advised by the laboratory
      responsible for the analysis of urine samples. We found a very strong statistical
      association between air sample measurements of DMF and NMF in the urine of the
      sample population (R(2) = 0.95, P < 0.0001). This study suggests that airborne
      exposure contributes significantly to elevated levels of NMF and, therefore,
      indicates that efforts should be concentrated on engineering controls in reducing
      workplace DMF exposure.

PMID- 11584116
TI  - Do electric patient beds reduce the risk of lower back disorders in nurses?
AB  - The aim of this study was to compare the probability estimates of lower back
      disorder (LBD) for a nurse performing a range of simulated patient care
      activities involving manual and electric patient beds. Studies of simulated
      patient care involving patient beds were undertaken using electrically powered
      and manually operated patient beds. The estimated probabilities of back injury,
      as calculated by the Lumbar Motion Monitor (LMM), between the two beds were
      compared statistically. A statistically significant reduction in LBD probability
      was observed in those functions that were completely achieved by the electrical
      mechanism. No significant difference in risk was observed in the patient care
      activities involving manipulating the patient in and around the bed that are more
      typical of 'heavy' orthopaedic nursing care in a busy acute ward environment. A
      potential for increased patient independence was observed during this trial. The
      LMM recorded no real risk reduction between situations involving electric or
      manual patient beds in those actions typically required of nurses in an acute
      orthopaedic ward caring for a disabled patient.

PMID- 11584117
TI  - Health and safety in the catering industry.
AB  - There is evidence that the catering industry has high levels of work-related
      injury and disease. This study examined the incidence, nature and causes of work
      related injury and disease among 315 catering students, at a large school of
      catering in the west of Ireland, over a 10 month academic year. A high incidence
      of accidents that caused injury was found. Cuts and lacerations, arising from
      accidents with knives, were the most common injuries seen, followed by burns and
      scalds from handling hot liquids. A significant level of work-related dermatitis
      was also recorded. Trainee chefs were identified as an occupational group with a
      high risk of occupational injury and disease. This group would benefit from
      vaccination against tetanus. Work-related injuries and disease generated a
      significant workload for the student health unit, which in itself is a good
      reason for catering establishments to make use of occupational health services.
      Health and safety procedures need to be audited and constantly reviewed at a
      local level. Further research is necessary to more accurately determine the
      incidence, nature and leading causes of work-related injury and disease in the
      catering industry in Ireland. This would help in the planning and implementation
      of an effective health and safety management system.

PMID- 11584118
TI  - Use of keyboards and symptoms in the neck and arm: evidence from a national
      survey.
AB  - The objective of this study was to examine the relationship between upper limb
      symptoms and keyboard use in a population survey. A questionnaire was mailed to
      21,201 subjects aged 16-64 years, selected at random from the registers of 34
      British general practices. Information was collected on occupation and on regular
      use of keyboards (for >4 h in an average working day), pain in the upper limbs
      and neck, numbness or tingling in the upper limbs, headaches, and feelings of
      tiredness or stress. Associations were explored by logistic regression, with the
      resultant odds ratios converted into prevalence ratios (PRs). Among 12,262
      respondents, 4899 held non-manual occupations. These included 1871 regular users
      of keyboards (e.g. computer operators, data processors, clerks, administrators,
      secretaries and typists). Pain in the neck or upper limbs and sensory symptoms
      were common in the non-manual workers overall (with 1 week period prevalences of
      30 and 15%, respectively), and were associated with older age, smoking, headaches
      and tiredness or stress. After adjustment for these factors, regular keyboard use
      was significantly associated with pain in the past week in the shoulders (PRs 1.2
      1.4) and the wrists or hands (PR 1.4), but not with elbow pain or sensory
      symptoms over the same period, or with neck or upper limb pain that prevented
      normal activities in the past year. Disabling symptoms were somewhat less
      prevalent among symptomatic keyboard users than among other symptomatic workers.
      We conclude that use of keyboards was associated with discomfort at the shoulder
      and wrist or hand, but risk estimates were lower than generally reported in
      workplace surveys. Previous estimates of risk in the occupational setting may
      have been biased by shared expectations, concerns, or other aspects of illness
      behaviour.

PMID- 11584119
TI  - Exposure to organic solvents during cosmetic finishing of cars.
AB  - The objectives of this study were to assess the exposure to organic solvents
      during degreasing, washing and polishing of cars, and to obtain information about
      acute health symptoms in car-finishing workers. Fifteen car shops participated in
      this study, and at these locations 36 workers had car finishing as their main
      working task. All 36 car-finishing workers and 17 randomly selected office
      workers from six of these car shops completed questionnaires on acute health
      symptoms. Personal monitoring of exposure to organic solvents was carried out in
      three representative shops. The highest exposure levels were found during
      degreasing of new cars, the median level of aliphatic hydrocarbons (C9-C13) being
      22 p.p.m. (range 7-215 p.p.m.). This exposure level represents 50% (range 20
      540%) of the Norwegian 8 h limit value for additive factor for these compounds.
      Only 28% of the workers used gas respirators regularly during this process. Very
      low exposure levels were detected during washing of second-hand cars and during
      polishing processes. The present study shows that car-finishing workers are
      exposed to high levels of organic solvents only for short periods of time. It
      seems that they are not adequately protected during these periods. However, the
      presence of acute symptoms was low, i.e. comparable to the prevalences in the
      reference group.

PMID- 11584120
TI  - Hand-arm vibration syndrome from exposure to high-pressure hoses.
AB  - Hand-arm vibration syndrome has been reported in the literature to occur
      following exposure to vibration from the use of many tools, but to date there
      have been no case reports of its occurrence in workers who have used high
      pressure hoses, alone or with other tools. To remedy this, the case histories of
      nine subjects (two without mixed exposure) examined in the UK and Canada are
      presented, together with their severity classified according to the Stockholm
      scales. Attention is drawn to the need to use multiple diagnostic tests to
      establish the diagnosis and the need to implement vibration isolation and damping
      methodologies, as and when feasible, with respect to hose nozzles in order to
      minimize the hazard. The ultimate goal for tool manufacturers, hygienists and
      engineers should be to reduce workplace vibration levels to meet national and
      international guidelines and legislation, including UK Health & Safety Executive
      guidelines and European Economic Community directives. The respective risk levels
      are presented, together with vibration measurements on hoses used by some of the
      cases.

PMID- 11584121
TI  - Neurological abnormalities associated with CDMA exposure.
AB  - Dysaesthesiae of the scalp and neurological abnormality after mobile phone use
      have been reported previously, but the roles of the phone per se or the
      radiations in causing these findings have been questioned. We report finding a
      neurological abnormality in a patient after accidental exposure of the left side
      of the face to mobile phone radiation [code division multiple access (CDMA)] from
      a down-powered mobile phone base station antenna. He had headaches, unilateral
      left blurred vision and pupil constriction, unilateral altered sensation on the
      forehead, and abnormalities of current perception thresholds on testing the left
      trigeminal ophthalmic nerve. His nerve function recovered during 6 months follow
      up. His exposure was 0.015-0.06 mW/cm(2) over 1-2 h. The implications regarding
      health effects of radiofrequency radiation are discussed.

PMID- 11584122
TI  - The Data Protection Act 1998 and the occupational physician.

PMID- 11584123
TI  - 'What occupation does the patient follow?'.

PMID- 11584124
TI  - How do we help refugees?

PMID- 11584126
TI  - Combining genetics and cell biology to crack the code of plant cell calcium
      signaling.
AB  - Plant hormones, light receptors, pathogens, and abiotic signals trigger
      elevations in the cytosolic calcium concentration, which mediate physiological
      and developmental responses. Recent studies are reviewed here that reveal how
      specific genetic mutations impair or modify stimulus-induced calcium elevations
      in plant cells. These studies provide genetic evidence for the importance of
      calcium as a second messenger in plant signal transduction. A fundamental
      question arises: How can different stimuli use the same second messenger,
      calcium, to mediate different responses? Recent research and models are reviewed
      that suggest that several important mechanisms contribute to specificity in
      calcium signaling in plant cells. These mechanisms include (i) activation of
      different calcium channels in the plasma membrane and organellar membranes, (ii)
      stimulus-specific calcium oscillation parameters, (iii) cell type-specific
      responses, and (iv) intracellular localization of calcium gradients and calcium
      elevations in plant cells.

PMID- 11584127
TI  - Biological weapons.

PMID- 11584128
TI  - Broadcast insensitivity.

PMID- 11584129
TI  - Bouncing back.

PMID- 11584131
TI  - Fate of dinosaurs.

PMID- 11584132
TI  - Food allergy: a problem on the increase.
AB  - It is thought that around 33% of anaphylactic reactions are caused by food, with
      peanuts causing a quarter of these life-threatening episodes. Given that the
      severity of symptoms, and in particular the frequency of anaphylactic shock,
      appears to rise with age, this will produce a public health problem of increasing
      magnitude in the future.

PMID- 11584133
TI  - Social insects and selfish genes.
AB  - Sometimes science advances because of a new idea. Sometimes, it's because of a
      new technique. When both occur together, exciting times result. In the study of
      social insects, DNA-based methods for measuring relatedness now allow
      increasingly detailed tests of Hamilton's theory of kin selection.

PMID- 11584134
TI  - Natures antibiotics: the potential of antimicrobial peptides as new drugs.
AB  - Animals and plants make a variety of substances to prevent potentially lethal
      infections. These include small antibiotic proteins, or peptides, which target
      bacteria, fungi and viruses. Research into these peptides not only give us an
      insight into how we naturally prevent infections, but can also provide us with
      new drugs to treat the ever-increasing danger of infections caused by antibiotic
      resistant bacteria.

PMID- 11584135
TI  - Yesterday's hair--human hair in archaeology.
AB  - Hair removed from archaeological burials can tell us a lot about the diet and
      lifestyle of our ancestors--information that may survive because of the unique
      biology of hair formation. But hair is also biodegradable and the effects of time
      and burial conditions can result in conflicting evidence of past lives.

PMID- 11584136
TI  - Bog bursts.
AB  - Variously attributed to earthquakes, lightening strikes, Acts of God, witchcraft,
      the wrath of the fairies, or the fertile Irish imagination, bog bursts are
      dramatic but poorly understood natural phenomena. This article attempts a
      scientific appraisal.

PMID- 11584137
TI  - The origin and spread of the new daisy rust in Britain.
AB  - Since 1997, wild and cultivated daisies in Britain and other European countries
      have been suffering from a rust fungus epidemic that menaces the future
      cultivation of horticultural varieties. The causal fungus was first discovered in
      Australia 100 years ago and may have evolved there from another rust fungus on
      daisies previously introduced from Europe. At present, ornamental daisies can be
      grown successfully only when protected by fungicide sprays.

PMID- 11584138
TI  - Sniffing out disease using the artificial nose.
AB  - Is there information in the odours that we emit and that circulate around us?
      More importantly, can doctors gain knowledge of disease by smelling their
      patients? Machines that emulate the mammalian nose have picked up the scent of
      several diseases and may drastically change diagnostic procedure.

PMID- 11584139
TI  - Who was... Harry Champion?
AB  - From insect collecting on the Surrey heaths, to forest management in Northern
      India, the rarefied atmosphere of Oxford University and the challenges of
      international consultancy, Harry Champion's life was rarely dull. As a schoolboy,
      he had declared his wish to travel widely and discover new species of plant and
      animal, though he probably never anticipated how far he would travel or how many
      species he would find.

PMID- 11584140
TI  - Immortality in a name.
AB  - Have you ever wondered where flora and fauna found their names? Many are named
      for people--rich and poor, large and small. Even tabletop football is not immune.

PMID- 11584141
TI  - Time is now for bold 21st century approaches for studying alcohol abuse and
      alcoholism.

PMID- 11584142
TI  - Increased ethanol self-administration in delta-opioid receptor knockout mice.
AB  - BACKGROUND: The role of the delta-opioid receptor in ethanol drinking has
      remained unclear despite the use of traditional pharmacological and correlational
      approaches. The results of several studies suggest that pharmacological blockade
      of these receptors results in decreases in ethanol drinking behavior, but an
      approximately equal number of reports have failed to observe an effect of delta
      receptor antagonism on ethanol drinking. It is clear that alternative approaches
      to understanding opioid-receptor involvement in ethanol drinking are needed.
      METHODS: In this study, ethanol drinking was examined in delta-opioid receptor
      knockout (KO) mice by using first a two-bottle-choice test, then an operant self
      administration paradigm and a second two-bottle-choice test, in that order. In
      addition, because KO mice were previously shown to display enhanced anxiety-like
      behavior relative to wild-type (WT) mice, the effect of ethanol self
      administration on anxiety-like responses was determined. RESULTS: delta KO mice
      initially showed no evidence of a preference for ethanol in the first two-bottle
      choice drinking test; however, after an experience of operant self-administration
      of ethanol, a preference for ethanol developed in the second two-bottle-choice
      test. KO mice also showed a preference for ethanol over water and self
      administered more ethanol than WT mice in the operant self-administration
      paradigm. The ethanol self-administered in this procedure was sufficient to
      reverse the innate anxiety-like response observed in this strain. CONCLUSIONS:
      delta KO mice showed a greater preference for ethanol and consumed more ethanol
      than their WT counterparts, suggesting that a decrease in delta-receptor activity
      is associated with increased ethanol-drinking behavior. It is hypothesized that
      delta receptors may influence ethanol self-administration at least partly through
      an effect of these receptors on anxiety-like behavior.

PMID- 11584143
TI  - Variation in alcohol pharmacokinetics as a risk factor for alcohol dependence.
AB  - BACKGROUND: The significant association between alcohol dehydrogenase (ADH)-2
      genotype and alcohol-dependence risk, demonstrated in both Asian and non-Asian
      populations, suggests a link between the metabolism of alcohol (ethanol) and
      individual differences in susceptibility to dependence. METHODS: We tested this
      hypothesis by following up on subjects who took part in the Alcohol Challenge
      Twin Study conducted in 1979-1981 and comparing the blood and breath alcohol
      results in that study between subjects who subsequently did or did not meet
      diagnostic criteria for lifetime alcohol dependence in 1992-1993. RESULTS:
      Subjects who met DSM-III-R criteria for lifetime alcohol dependence at follow-up
      had higher blood and breath alcohol values after alcohol challenge than never
      dependent subjects. Multivariate analysis showed independent effects of
      susceptibility to alcohol dependence and smoking status on blood alcohol
      concentrations, whereas habitual alcohol intake at the time of the initial study
      had marginally significant effects. The risk of alcohol dependence was 2-fold
      higher in men and 3-fold higher in women with blood or breath alcohol
      concentrations in the highest quartile than in the lowest quartile. CONCLUSIONS:
      In view of this association and the known genetic influences on both alcohol
      pharmacokinetics and alcohol dependence, it is probable that part of the
      heritability of dependence is mediated by genes (other than the known ADH2 and
      ADH3 polymorphisms) affecting alcohol metabolism.

PMID- 11584144
TI  - Association of the ADH2 genotypes with skin responses after ethanol exposure in
      Japanese male university students.
AB  - BACKGROUND: A contribution of the alcohol dehydrogenase-2 (ADH2) polymorphism to
      alcohol sensitivity and alcohol drinking behavior is still controversial. In this
      study, we examined the effects of the ADH2 genotypes on skin reactions to ethanol
      and habitual alcohol intake among Japanese male university students, controlling
      for the effects of the low Km aldehyde dehydrogenase (ALDH2) genotype, as an
      extension of our previous study. METHODS: The study subjects were 357 Japanese
      male students [average age (mean +/- SD) was 23.7 +/- 3.0 years] in a medical
      university. The subjects completed a questionnaire regarding self-reported
      alcohol-associated symptoms and alcohol-drinking behavior. The ADH2 and ALDH2
      genotypes were determined through digestion of polymerase chain reaction products
      by restriction enzymes. All subjects participated in the ethanol patch test. We
      observed skin responses at 0, 5, 15, and 20 min after removal of the tape.
      RESULTS: Among the ALDH2*1/*1 genotypes, only some subjects with ADH2*1/*2 or
      ADH2*2/*2 exhibited a positive response, which increased with increasing time
      after the removal. However, none of comparisons between the different ADH2
      genotypes reached statistical significance. Among the ALDH2*1/*2 genotypes, those
      with ADH2*1/*2 or ADH2*2/*2 showed a significant increase in response with
      increasing time after the removal and revealed a significantly higher positivity
      rate at 15 min than those with ADH2*1/*1. In those with the ALDH2*1/*2 genotype,
      the positive rate of facial flushing with one glass of beer was higher in those
      with ADH2*1/*2 and ADH2*2/*2 than those with ADH2*1/*1, although this was not
      significant. However, the ADH2 genotype did not seem to influence drinking
      frequency or amounts of alcohol intake in each ALDH2 genotype. CONCLUSIONS: This
      study finds further evidence for a contribution of the ADH2 polymorphism to skin
      reactions after either local or systemic ethanol exposure in Asian people.
      However, the effects of the ADH2 polymorphism may be mild because this
      polymorphism does not seem to influence alcohol drinking behavior in these study
      subjects.

PMID- 11584145
TI  - Chronic ethanol consumption differentially alters GABA(A) receptor alpha1 and
      alpha4 subunit peptide expression and GABA(A) receptor-mediated 36 Cl(-) uptake
      in mesocorticolimbic regions of rat brain.
AB  - BACKGROUND: Gamma-aminobutyric acid type A (GABA(A)) receptors in the brain are
      modulated by chronic ethanol exposure via the regulation of their function and
      expression throughout the central nervous system. Recent studies show that
      chronic ethanol exposure alters subsequent ethanol self-administration, effects
      that are believed to be mediated by subcortical regions of the rat brain
      including the amygdala (AMG), the nucleus accumbens (NAC), and the ventral
      tegmental area (VTA). METHODS: We evaluated GABA(A) receptor subunit expression
      using subunit specific (alpha1 and alpha4) immunoblotting of small tissue punches
      from AMG, NAC, and VTA. GABA(A) receptor-mediated 36 Cl- uptake was measured in
      these brain areas after chronic ethanol consumption for 2 weeks. RESULTS:
      Regional differences in the effect of chronic ethanol on alpha1 and alpha4
      subunit expression were found. In the AMG, alpha1 and alpha4 subunit expressions
      were significantly decreased by 21.1 +/- 5.5% and 22.0 +/- 7.1%, respectively. In
      the NAC, there was a decrease of 28.1 +/- 1.3% in alpha4 subunit expression (p <
      0.0001), but no change in alpha1 subunit expression was observed. In the VTA,
      there were no changes in alpha1 and alpha4 subunit expressions. Muscimol
      stimulated Cl- uptake was enhanced in the extended AMG, but not the extended NAC
      of ethanol-dependent rats. The muscimol concentration response curve was left
      shifted with a 74% decrease (p < 0.01) in the EC50 and a 42% increase (p < 0.05)
      in the Emax in the AMG of ethanol-dependent rats. CONCLUSIONS: These results
      suggest that chronic ethanol exposure alters GABA(A) receptor expression in the
      AMG and NAC. Decreased expression of alpha4 subunits is associated with increases
      in GABA(A) receptor function in the AMG, but not the NAC. These changes may
      contribute to alcohol drinking behavior and the development of ethanol
      dependence.

PMID- 11584146
TI  - Acamprosate is neuroprotective against glutamate-induced excitotoxicity when
      enhanced by ethanol withdrawal in neocortical cultures of fetal rat brain.
AB  - BACKGROUND: Acamprosate reduces relapse, and the drug may interact with glutamate
      transmission and with glutamate/NMDA receptors. Because these systems are
      implicated in excess calcium entry leading to alcohol withdrawal-induced
      neurotoxicity, we evaluated the effects of acamprosate on these parameters in
      neuronal cultures. METHODS: Primary cultures of neocortical neurons from fetal
      Sprague-Dawley rats were maintained either in normal medium or in medium
      containing 100 mM ethanol for 4 days. After this time, cultures were challenged
      with glutamate for 10 min and then returned to medium (all in the absence of
      ethanol). 45Ca2+ uptake was measured during the challenge, and glutamate-induced
      toxicity was assessed after 20 hr. The effects of acamprosate present during the
      glutamate challenge were measured on both parameters. RESULTS: In controls,
      acamprosate did not significantly affect glutamate-induced neurotoxicity but
      produced a significant inhibition of calcium entry. The NMDA receptor antagonists
      dizocilpine and d-amino-phosphonovalerate (D-APV) inhibited both glutamate
      neurotoxicity and calcium entry. In cultures previously exposed to ethanol,
      glutamate-induced neurotoxicity and calcium entry were both significantly
      enhanced. Dizocilpine reduced both these parameters to unstimulated control
      values, and D-APV reduced both calcium entry and neurotoxicity with the same
      relation that we obtained in control cultures. In the ethanol-withdrawn cultures,
      acamprosate reduced both the enhanced glutamate-induced calcium entry and the
      enhanced neurotoxicity in a concentration-dependent manner. Acamprosate also
      significantly reduced calcium entry caused by 80 mM K+ in control and ethanol
      exposed cultures. CONCLUSIONS: Acamprosate had protective effects against
      glutamate-induced neurotoxicity only in ethanol-withdrawn cultures. The
      neuroprotective effects of the drug did not correlate with its effects on calcium
      entry, making it unlikely that acamprosate directly affects NMDA receptors via
      the glutamate binding site or the receptor-operated calcium channel. The results
      are, however, compatible with other inhibitory effects on NMDA receptor function.

PMID- 11584147
TI  - A social learning perspective: a model of parenting styles, self-regulation,
      perceived drinking control, and alcohol use and problems.
AB  - BACKGROUND: This investigation sought to determine how different parenting styles
      are related to general self-regulatory processes that are linked to alcohol use
      and abuse. Self-regulation and, more specifically, thoughts of control over
      drinking are forms of positive self-control mechanisms. Parenting styles are
      known determinants of both negative and positive self-control mechanisms in
      offspring. According to social learning theory, stronger relationships between
      parenting style and self-regulatory processes would be expected from the parent
      who is the same sex as the respondent. METHODS: A total of 144 female and 107
      male college students currently using alcohol were administered a questionnaire
      on their alcohol use and problems, perceived style of parenting (authoritarian,
      permissive, or authoritative) of their parents, self-regulation, and perceived
      control of drinking. A model linking parenting styles, self-regulatory processes,
      and control over drinking with alcohol use and alcohol problems was tested across
      sex groups by using structural equation modeling. RESULTS: In general, the
      parenting style of the parent of the same sex as the respondent's was found to be
      significantly related to self-regulation, which is known to be protective against
      alcohol use and abuse. A permissive parent of the same sex as the respondent was
      negatively associated with good self-regulatory processes for both men and women.
      Having an authoritative mother was also shown to be related to higher levels of
      self-regulation for women. CONCLUSIONS: Self-regulation mediated the pathway from
      a permissive parenting style to perceived drinking control, which, in turn,
      mediated the pathway from self-regulation to alcohol use and problems. Finally,
      self-regulation mediated the positive pathway from an authoritative mother to
      perceived control over drinking for women.

PMID- 11584148
TI  - Alcohol use disorders and anxiety disorders: relation to the P300 event-related
      potential.
AB  - BACKGROUND: The robust association of alcoholism with reduced P300 event-related
      potential amplitude has been largely established in severely affected alcoholics
      and their offspring. Few studies have examined the relationship of increased
      arousal, anxiety, and P300. In this study, we sought to determine whether P300
      group differences could be discerned in well functioning individuals with less
      severe forms of alcohol use disorders and anxiety disorders. We were particularly
      interested in looking at the subgroup of alcohol use disorders accompanied by
      anxiety disorders. This subgroup has previously been found to have diminished
      alpha amplitude in the resting EEG. METHODS: Male and female community volunteers
      (99 unrelated index participants and 78 relatives) and 21 unrelated volunteers
      from an anxiety disorder clinic were interviewed by using the Schedule for
      Affective Disorders and Schizophrenia, Lifetime version. Blind-rated lifetime
      psychiatric diagnoses were assigned according to DSM-III-R criteria. Auditory and
      visual P300 event-related potentials were elicited with an oddball paradigm and
      were recorded at the midparietal (Pz) site. RESULTS: As expected, auditory P300
      amplitudes were significantly reduced in participants with alcohol use disorders
      and significantly increased in participants with lifetime anxiety disorders.
      However, more detailed analysis revealed that, in an apparent paradox, auditory
      P300 amplitudes were lowest in individuals with comorbid alcohol use and anxiety
      disorders and highest in individuals with anxiety disorders alone. Visual P300
      amplitudes followed the same trends but were generally not significant.
      CONCLUSIONS: Even in a sample of largely community-ascertained individuals,
      auditory P300 amplitude is reduced in alcoholics, particularly those with anxiety
      disorders, and is highest in nonalcoholics with anxiety disorders.

PMID- 11584149
TI  - Acute, rapid, and chronic tolerance during ontogeny: observations when equating
      ethanol perturbation across age.
AB  - BACKGROUND: Sensitivity to the motor-impairing and hypnotic effects of ethanol
      (EtOH) increases notably during development. Less is known, however, about the
      ontogeny of EtOH tolerance and the ontogenetic relationship among different types
      of tolerance. Consequently, we compared the ontogenetic development of acute,
      rapid, and chronic tolerance to EtOH-induced motor impairment and hypothermia in
      a swim task. METHODS: Preweanling, adolescent, and adult female and male Sprague
      Dawley rats were given chronic saline (control group), five daily EtOH exposures
      before EtOH on test day (chronic group), one EtOH exposure before test day (rapid
      group), or EtOH exposure only on test day (acute groups). Separate groups of
      animals in the acute groups were tested at 15, 60, or 105 min after injection to
      estimate acute tolerance development via calculating slopes of the linear
      regression of impairment relative to brain alcohol levels at each postinjection
      interval. Initial EtOH perturbation of swim performance was equated across age by
      varying EtOH dose. RESULTS: Acute tolerance was evident to the motor-impairing
      effects of EtOH at all ages. When impairment was indexed relative to brain
      alcohol levels, rapid and chronic tolerance to the motor-impairing effects of
      EtOH on latency to reach the start was seen across age, although this tolerance
      tended to be more pronounced in adults. Somewhat different ontogenetic patterns
      of tolerance development were observed with EtOH-induced hypothermia, a dependent
      measure for which EtOH perturbation was not equated across age. CONCLUSIONS: The
      degree of initial perturbation by EtOH seems to be an important predictor of
      tolerance expression during ontogeny. That is, ontogenetic profiles of tolerance
      development differ significantly when EtOH-induced motor impairment is equated
      across age rather than dose of EtOH administered. The role of target response
      measures and context stress should also be considered when exploring ontogenetic
      expression of EtOH tolerance.

PMID- 11584150
TI  - Alcohol-naive alcohol-preferring (P) rats exhibit higher local cerebral glucose
      utilization than alcohol-nonpreferring (NP) and Wistar rats.
AB  - BACKGROUND: The present study determined local cerebral glucose utilization
      (LCGU) rates in alcohol-naive alcohol-preferring (P), alcohol nonpreferring (NP),
      and outbred Wistar rats to test the hypothesis that innate differences in
      functional neuronal activity are present in limbic regions as a result of
      selective breeding for high-alcohol drinking behavior. METHODS: All procedures
      were conducted during the dark cycle. 2-[14C]deoxyglucose ([14C]2-DG; 125
      microCi/kg) was injected intravenously and timed arterial blood samples were
      collected during the following 45 min and assayed for glucose and [14C]2-DG
      content. Rats were then decapitated, the brains removed and frozen to -70 degrees
      C, and 20 microm coronal sections were prepared for quantitative autoradiographic
      analysis. RESULTS: Rates of LCGU were determined in 55 regions and subregions,
      including limbic, cortical, and subcortical structures. LCGU rates were
      significantly (p < 0.01) higher in several limbic (e.g., ventral tegmental area,
      nucleus accumbens shell, olfactory tubercle, medial prefrontal cortex, and
      lateral hypothalamus), cortical (e.g., parietal, temporal, occipital, cingulate,
      piriform, and entorhinal), and subcortical (e.g., thalamus, habenula, preoptic
      area, and striatum) regions in P rats, compared with NP and Wistar rats, whereas
      rates in Wistar rats were higher in a few regions (e.g., CA1 and CA3 regions of
      the posterior hippocampus) than NP rats. CONCLUSIONS: The data suggest that
      selective breeding for high-alcohol drinking produces intrinsically higher
      functional neuronal activity in the central nervous system regions of the high
      alcohol consuming P line compared with low-alcohol drinking NP or Wistar rats,
      although these differences may not generalize to other rat lines selectively bred
      for divergent alcohol drinking.

PMID- 11584151
TI  - Effects of CB1 cannabinoid receptor blockade on ethanol preference after chronic
      ethanol administration.
AB  - BACKGROUND: Chronic ethanol administration results in neurobiological alterations
      similar to those observed after chronic cannabinoid exposure. The purpose of this
      study was to investigate alcohol drinking and the withdrawal responses after
      pulmonary chronic alcoholization with intraperitoneal or oral administration of a
      cannabinoid CB1 receptor antagonist. METHODS: The cannabinoid receptor antagonist
      SR141716A, 1, 3 or 10 mg/kg/day intraperitoneally or orally, was administered to
      Wistar rats either during a 30-day chronic ethanol exposure or at the cessation
      of this procedure. Motility was recorded during 18 hr after the cessation of
      chronic alcoholization just before the beginning of the free-choice paradigm
      (water versus alcohol 10% v/v). RESULTS: A significant increase in ethanol
      preference was observed during the free-choice paradigm after chronic
      alcoholization with concurrent SR141716A administration (3 or 10 mg/kg/day). A
      significant decrease in withdrawal motility after administration of SR141716A was
      observed with only the highest dose (10 mg/kg/day). The administration of
      SR141716A, 3 or 10 mg/kg/day, after chronic pulmonary alcoholization
      significantly decreased the preference for alcohol. Finally, a significant
      decrease in ethanol preference was seen during the free-choice paradigm of
      nonalcoholized rats treated with SR141716A, 3 or 10 mg/kg/day, during 30 days
      before the free-choice paradigm. CONCLUSIONS: The concurrent administration of
      the CB1 antagonist together with the chronic alcoholization increases the
      preference for ethanol. Also, the administration of the CB1 antagonist after the
      chronic alcoholization or at the time of withdrawal drastically diminishes the
      ethanol preference.

PMID- 11584152
TI  - Divalproex sodium in alcohol withdrawal: a randomized double-blind placebo
      controlled clinical trial.
AB  - BACKGROUND: Divalproex sodium, an anticonvulsant and antikindling agent and gamma
      aminobutyric acid enhancer, has been proposed as an alternative to
      benzodiazepines for treating alcohol withdrawal. This study reports on a
      randomized, double-blind, placebo-controlled trial of divalproex sodium in acute
      alcohol withdrawal. METHODS: Thirty-six hospitalized patients experiencing
      moderate alcohol withdrawal as measured by a score of at least 10 on the revised
      Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) were
      randomized to receive either divalproex sodium 500 mg three times per day for 7
      days or matched placebo in a double-blind manner. All subjects received a
      baseline dose of oxazepam and had additional oxazepam available as a rescue
      medication in accordance with a standard, symptom-triggered detoxification
      protocol. Mean total milligrams of oxazepam received, progression of withdrawal
      symptoms, psychological distress as measured by the Symptom Checklist-90, side
      effects, and adverse outcomes were compared between groups. RESULTS: Use of
      divalproex sodium resulted in less use of oxazepam (p < 0.033). Group differences
      seemed primarily driven by those subjects who experienced symptoms above
      threshold level (CIWA-Ar >or=10) after 12 hr. The progression in severity of
      withdrawal symptoms (increase in CIWA-Ar above baseline) was also significantly
      greater in the placebo group (p < 0.05). CONCLUSIONS: This placebo-controlled
      pilot study suggests that divalproex sodium significantly affects the course of
      acute alcohol withdrawal and reduces the need for treatment with a
      benzodiazepine. A more aggressive loading dose strategy may demonstrate a more
      robust or earlier response.

PMID- 11584153
TI  - Utility of a new assay for carbohydrate-deficient transferrin (Biorad %CDT TIA)
      to monitor abstinence during a treatment outcome study.
AB  - BACKGROUND: The ability to reliably detect heavy alcohol use is important in both
      clinical and research populations. The current study evaluates the utility of the
      newest method of measuring carbohydrate deficient transferrin (CDT) in monitoring
      the abstinence during a treatment outcome study. METHODS: Blood from 40 alcohol
      dependent individuals was obtained at baseline and at weeks 4, 8, and 12 of
      treatment. Differences in percent of baseline GGT and %CDT levels were analyzed
      in people who remained abstinent throughout treatment (abstainers) and in those
      who consumed alcohol during treatment (drinkers). RESULTS: There was a
      significant decrease in the percent of baseline %CDT levels in the subjects who
      abstained at week 4 and a trend at weeks 8 and 12. Conversely, there were no
      significant differences in percent of baseline GGT levels between drinkers and
      abstainers at any time point. CONCLUSIONS: Although small in nature, this study
      provides preliminary evidence for the use of the relatively new Biorad %CDT assay
      to monitor drinking status during treatment outcome studies. This study is also
      consistent with previously reported findings that GGT appears to be less
      sensitive than %CDT in detecting the consumption of alcohol. A larger trial
      focusing on sex differences in the utility of % CDT to monitor outcome would be
      of interest.

PMID- 11584154
TI  - Efficacy of naltrexone and acamprosate for alcoholism treatment: a meta-analysis.
AB  - BACKGROUND: Renewed interest in medications to prevent relapse in alcoholics
      (i.e., antidipsotropics) resulted in approval by the Food and Drug Administration
      of naltrexone to treat alcohol dependence. Acamprosate, although not approved in
      the United States, is used in alcoholism treatment in many other parts of the
      world. In the absence of studies that compare the effects of these medications,
      we used a meta-analytic approach to the literature to compare their efficacy in
      alcoholism treatment. METHODS: All published placebo-controlled trials of
      naltrexone or acamprosate for alcohol dependence were examined, and, when
      suitable, data were extracted for calculation of a mean effect size. A sample of
      studies of selective serotonin reuptake inhibitors for treatment of major
      depression conducted over the last two decades served as a comparator for the
      antidipsotropics. RESULTS: Both antidipsotropics exerted significant, but modest,
      effects on treatment retention and/or drinking outcomes. There was significant
      variability among the studies for the measure on which the largest effect was
      exerted by each of these medications. Based on limited comparisons of the two
      medications, there appears to be no statistical difference in their efficacy in
      the treatment of alcohol dependence. In contrast, there was a consistent effect
      of selective serotonin reuptake inhibitors on depressive symptoms in major
      depression, which was significantly greater than the effects observed for the
      antidipsotropics. CONCLUSIONS: Both naltrexone and acamprosate are efficacious in
      reducing alcohol consumption in alcoholics. However, their specific role in
      alcoholism treatment remains to be more clearly defined. New approaches to the
      use of these medications and development of new medications are needed if
      pharmacotherapy is to play a substantial role in the treatment of alcoholism.

PMID- 11584155
TI  - Screening for high- and moderate-risk drinking during pregnancy: a comparison of
      several TWEAK-based screeners.
AB  - PURPOSE: This study investigated the use of the TWEAK and nine alternative
      screeners for predicting high-risk and moderate-risk drinking during pregnancy.
      METHOD: The analysis was based on self-reports from 404 lifetime drinkers who
      presented for an initial visit at nine prenatal clinics in Washington, DC. Data
      were collected anonymously by having women directly enter their responses onto an
      audio, computer-assisted interview that was programmed onto a laptop computer.
      Pregnancy risk drinking status was based on both average daily volume of intake
      and frequency of drinking 3+ drinks in a day. Each of the alternative screeners
      was constructed by adding one additional risk indicator to the TWEAK, and three
      different scoring options were explored. RESULTS: Using thresholds of 2 points
      for high-risk drinking and 1 point for moderate-risk drinking, the TWEAK
      demonstrated a sensitivity and specificity of 70.6% and 73.2% for high-risk
      drinking and a sensitivity and specificity of 65.6% and 63.7% for any (high- or
      moderate-) risk drinking during pregnancy. None of the alternative screeners
      resulted in significant improvement, but the addition of current smoking status
      showed enough promise to warrant further testing in larger samples. CONCLUSIONS:
      Despite some loss in sensitivity and specificity, the TWEAK, in its original or a
      modified form, can be extended to measures of high-risk drinking that incorporate
      infrequent heavy intake and can be used to test for moderate- as well as high
      risk drinking. Because identification of moderate-risk drinkers substantially
      increases the pool of women targeted for intervention, cost implications must be
      considered in designing appropriate interventions.

PMID- 11584156
TI  - Health problems in adolescents with alcohol use disorders: self-report, liver
      injury, and physical examination findings and correlates.
AB  - BACKGROUND: Although adolescent alcohol consumption has been found to be
      positively correlated with self-reported health problems, few studies have
      examined other health indicators. This study compared adolescents with alcohol
      use disorders (AUDs) and a community reference group on self-reported health
      problems, serum liver enzymes, and physical examination findings. The relevance
      of negative emotionality to understanding these health problems was also
      investigated. METHODS: The subjects were adolescents with AUDs recruited from
      clinical programs and classified as having DSM-IV alcohol dependence (n = 71) or
      alcohol abuse (n = 57) and reference adolescents without AUDs recruited from
      community sources (n = 131). The assessment of health status included self
      reported health problems in 15 areas; serum liver enzyme assays, including gamma
      glutamyl transpeptidase, alanine aminotransferase, and aspartate
      aminotransferase; and physical examination findings. Negative emotionality was
      determined by systematically combining scores from the Hamilton Anxiety Rating
      Scale, the Beck Depression Inventory, the Child Behavior Checklist, and the
      Multidimensional Personality Questionnaire. RESULTS: Adolescent AUDs were
      associated with more self-reported health problems, higher gamma-glutamyl
      transpeptidase and alanine aminotransferase levels, and more physical examination
      abnormalities. Negative emotionality was highly correlated with self-reported
      health problems, mediated the relationship between AUDs and self-reported health
      problems, and was not correlated with serum liver enzyme levels or physical
      examination abnormalities. CONCLUSIONS: These results indicated that AUDs during
      adolescence were associated with health problems, including modest but
      demonstrable liver injury. Self-reported health problems were probably best
      understood, in this context, as a negative emotionality manifestation.

PMID- 11584157
TI  - Long-term alcohol exposure changes sensitivity of rat Kupffer cells to
      lipopolysaccharide.
AB  - BACKGROUND: Chronic ethanol treatment enhances Kupffer cell sensitivity to
      lipopolysaccharide (LPS). In this model, CD14 in Kupffer cells was increased
      significantly 4 weeks after ethanol. Moreover, it was shown that prostaglandin E2
      produced by activated Kupffer cells participated in the mechanism of ethanol
      induced fatty liver. This study was designed to elucidate the temporal effect of
      chronic ethanol exposure on Kupffer cell sensitization to LPS. METHODS: Rats were
      given ethanol every 24 hr intragastrically for up to 12 weeks, and Kupffer cells
      were isolated 24 hr after the final ethanol administration and cultured in RPMI
      1640 with 10% fetal bovine serum. After addition of LPS to Kupffer cells,
      intracellular calcium ([Ca2+]i) was measured. RESULTS: CD14 in Kupffer cells was
      increased approximately 2-fold, and then it decreased and returned to control
      levels. The LPS-induced increases in [Ca2+]i and tumor necrosis factor-alpha by
      Kupffer cells were also increased approximately 3-fold over control values, but
      they also returned to control levels. Triglyceride content increased with the
      duration of chronic ethanol treatment. At 8 weeks, prostaglandin E2 produced by
      Kupffer cells increased approximately 3-fold over control values and
      triglycerides by approximately 4-fold before gradually decreasing to basal
      levels. After 12 weeks of ethanol exposure, LPS-induced increases in [Ca2+]i and
      tumor necrosis factor-alpha production were only approximately 50% as high as
      peak levels at 4 weeks. Liver triglyceride content at 12 weeks was reduced
      significantly compared with values at 8 weeks. CONCLUSIONS: Kupffer cells at the
      early stage of chronic ethanol exposure exhibited sensitization to LPS, but this
      sensitivity was blunted later. This correlated with triglyceride accumulation in
      the liver. These data indicate that long-term alcohol exposure changes the
      sensitivity of rat Kupffer cells to LPS but that the magnitude of the effect is
      time dependent.

PMID- 11584158
TI  - Effect of beta-carotene on hepatic cytochrome P-450 in ethanol-fed rats.
AB  - BACKGROUND: Hepatotoxicity of ethanol is increased by beta-carotene in both
      rodents and nonhuman primates. Furthermore, in smokers who are also drinkers,
      beta-carotene increases the incidence of pulmonary cancer. The hepatotoxicity was
      associated with proliferation of the membranes of the smooth endoplasmic
      reticulum, suggesting the involvement of cytochromes P-450. Therefore, the aim of
      the present study was to assess the effect of beta-carotene and ethanol treatment
      on rodent hepatic cytochromes P-450. METHODS AND RESULTS: Weanling male Sprague
      Dawley rats were pair-fed beta-carotene (56.5 mg/l of diet) for 8 weeks, with and
      without ethanol (Lieber-DeCarli, 1994 liquid diet). As expected, ethanol
      increased CYP2E1 (measured by Western blots) from 67 +/- 8 to 317 +/- 27
      densitometric units (p < 0.001). Furthermore, beta-carotene potentiated the
      ethanol induction to 442 +/- 38 densitometric units (p < 0.01) with a significant
      interaction (p = 0.012). The rise was confirmed by a corresponding increase in
      the hydroxylation of p-nitrophenol, a specific substrate for CYP2E1, and by the
      inhibition with diethyl dithiocarbamate (50 microM). Beta-carotene alone also
      significantly induced CYP4A1 protein (328 +/- 49 vs. 158 +/- 17 densitometric
      units, p < 0.05). The corresponding CYP4A1 mRNA (measured by Northern blots) was
      also increased (p < 0.05) and there was a significant interaction of the two
      treatments (p = 0.015). The combination of ethanol and beta-carotene had no
      significant effect on either total cytochrome P-450 or CYP1A1/2, CYP2B, CYP3A,
      and CYP4A2/3 contents. CONCLUSIONS: Beta-carotene potentiates the CYP2E1
      induction by ethanol in rat liver and also increases CYP4A1, which may, at least
      in part, explain the associated hepatotoxicity.

PMID- 11584159
TI  - Alcohol impairs protein synthesis and degradation in cultured skeletal muscle
      cells.
AB  - BACKGROUND: Acute and chronic alcohol intoxication decreases skeletal muscle
      protein synthesis under in vivo conditions. We investigated whether ethanol
      (EtOH) and its major metabolites, acetaldehyde and acetate, can directly modulate
      protein balance under in vitro conditions. METHODS: Human myocytes were incubated
      with different doses of EtOH for varying periods of time (i.e., 4-72 hr).
      Alternatively, cells were incubated with acetaldehyde, acetate, insulin, insulin
      like growth factor-I (IGF-I), or with a combination of EtOH plus insulin or IGF
      I. Rates of protein synthesis or degradation were determined by 35S
      methionine/cysteine incorporation into or release from cellular protein. RESULTS:
      A significant, 15% to 20%, decrease in basal protein synthesis was observed after
      24 hr, but not at earlier time points, in response to 80 mM EtOH. Incubation of
      myocytes for 72 hr decreased synthesis in cells incubated with EtOH ranging
      between 60 and 120 mM. The ability of IGF-I or insulin to stimulate protein
      synthesis was impaired by 30% and 60%, respectively, in cells incubated with 80
      mM EtOH for 72 hr. Exposure of cells to 200 microM acetaldehyde or 5 mM Na
      acetate also decreased basal protein synthesis. In contrast, neither EtOH,
      acetaldehyde, nor acetate altered the basal rate of protein degradation. However,
      EtOH completely impaired the ability of insulin and IGF-I to inhibit proteolysis.
      Finally, EtOH did not impair IGF-I receptor autophosphorylation, but inhibited
      the ability of insulin to phosphorylate its own receptor. EtOH also did not alter
      the number of insulin or IGF-I receptors or the formation of insulin/IGF-I hybrid
      receptors. CONCLUSIONS: We have demonstrated that EtOH can directly inhibit
      muscle protein synthesis under in vitro conditions. Neither EtOH nor its
      metabolites altered basal protein degradation, although EtOH did compromise the
      ability of both insulin and IGF-I to slow proteolysis. This impairment seems to
      be mediated by different defects in signal transduction.

PMID- 11584160
TI  - Moderate alcohol during pregnancy: learning and behavior in adolescent rhesus
      monkeys.
AB  - BACKGROUND: Although high-dose prenatal alcohol exposure is related to cognitive
      and behavioral impairments in children and adolescents with fetal alcohol
      syndrome, there is relatively little research on the effects of moderate drinking
      during pregnancy. We examined learning, memory, and behavior in adolescent rhesus
      monkeys prenatally exposed to moderate levels of alcohol, psychological stress,
      or both alcohol and stress. METHODS: Forty adolescent rhesus monkey subjects were
      derived from four groups of female rhesus monkeys that (1) consumed alcohol
      throughout gestation; (2) experienced prenatal stress; (3) experienced prenatal
      stress and alcohol consumption; or (4) control group (no alcohol, no stress). The
      subjects were assessed for number of trials required to reach 90% criterion of
      correct responses on nonmatching-to-sample task (NMS), followed by trials with
      delays of 30, 60, or 120 sec. Ratings of behavior during testing were made after
      each session. RESULTS: Subjects exposed to moderate prenatal alcohol required
      significantly more trials to reach criterion on the acquisition phase of the NMS
      task but had no difficulty with delays. Prenatally stressed monkeys showed lower
      response inhibition or less behavioral restraint, whereas prenatal alcohol plus
      stress monkeys showed higher activity level and stereotypies compared with
      controls. High scores on neonatal measures of orientation (attending to novel
      stimuli) and motor maturity and low scores on irritability, activity,
      stereotypies, and impulsivity during acquisition were correlated with fewer
      trials to criterion on acquisition of NMS. CONCLUSIONS: NMS trials required to
      reach criterion and behavior during testing are sensitive to moderate-level
      prenatal alcohol exposure in monkeys. The most adverse behavioral outcomes
      (hyperactivity and stereotypies) were associated with prenatal alcohol plus
      stress, raising concerns that environmental stress might provide the context
      within which fetal alcohol exposure could promote adverse behavioral outcomes.
      These effects occurred in the absence of either facial deformities or retarded
      physical growth.

PMID- 11584163
TI  - Current status of MIDCAB procedure.
AB  - The advent of cardiopulmonary bypass in the early 1960s allowed surgeons to
      safely perform complex reconstructions on the heart. Since then, the field of
      cardiac surgery has progressed to where surgical myocardial revascularization, or
      coronary artery bypass grafting (CABG), has become the most exhaustively studied
      operation in the history of surgery, and it has achieved widespread use because
      its benefits have been so thoroughly documented. The paradoxical fact is that
      more elderly and debilitated patients benefit the most from cardiac surgery
      compared with medical therapy, yet they sustain greater risk of morbidity and
      mortality after cardiac surgery. Most of the recent innovations and refinements
      in the treatment of coronary artery disease aim toward reduction of trauma
      without deviating much from the safety and efficacy of the conventional
      procedures. As a consequence, a greater number of high-risk elderly patients have
      become candidates for coronary artery bypass grafting (CABG). All of the
      amendments are caused by changing clinical scenarios brought on by an increased
      number of aging patients, a greater number of patients requiring re-operations,
      cost containment, increased discernment about outcome assessment, and also the
      dominance of coronary bypass being threatened by the success of interventional
      cardiology.

PMID- 11584161
TI  - Finding paradigms for the future of alcoholism research: an interdisciplinary
      perspective.
AB  - This is a review article and critique of current research strategies in the
      alcohol field. Although the alcohol field is proud of its multidisciplinary
      tradition and scientific findings within specific disciplines, there are very few
      models of cross-disciplinary research and communication. Currently, the favored
      model of risk is genetic; the favored model of pathophysiology is molecular
      neuroscience; and the favored model of clinical investigation is narrowly
      categorical. If there is a hierarchy within science that is based on explanatory
      power, then models of alcoholism emerging from neuroscience, molecular biology,
      and genetics should be able to accommodate (if not account for) the findings on
      clinical aspects of alcohol dependence, as well as data on differential risk,
      course, and recovery that come from the behavioral and social sciences. The first
      section of this article reviews the most popular models of alcohol dependence
      over the past 40 years. I argue that the currently fashionable categorical
      approach to diagnosis in DSM-IV (and ICD-10) has failed to serve as a framework
      for interdisciplinary research and has failed to meet the needs of human
      geneticists, population-based researchers, psychosocial researchers, basic
      scientists working in animal models, and patient-oriented researchers. I argue
      for a return to the dimensional approach to diagnosis in the alcohol dependence
      syndrome construct. In the second section of the article, I lay out an agenda for
      revitalized patient-oriented research in the alcohol field, as a bridge between
      basic biological research and innovations in clinical practice, as well as the
      key to a valid diagnostic system that can inform research strategies in genetics
      and population-based research. In the third section of the article, I highlight
      the interface between genetic and psychosocial models of risk and propose a
      possible structure for future collaboration. I conclude with a plea to funding
      agencies and investigators to translate discipline-based scientific findings into
      a science relevant to alcoholism by addressing the challenges and opportunities
      of an interdisciplinary research agenda on the pathophysiology of alcohol
      dependence and the multidimensional sources of risk.

PMID- 11584164
TI  - Neurological and cognitive disorders after coronary artery bypass grafting.
AB  - Cerebral injury is a major cause of mortality and morbidity of coronary artery
      bypass grafting. Stroke occurs in 3% of patients and is largely caused by
      embolization of atheromatous debris during manipulation of the diseased aorta.
      Cognitive impairment, which is predominantly caused by microembolization of
      gaseous and particulate matter, mainly generated by cardiotomy suction, is more
      common. Demonstration of similar cognitive impairment in patients operated on
      without cardiopulmonary bypass indicates that other pathophysiological
      mechanisms, such as anaesthesia and hypoperfusion, are also involved. Advances in
      medical, anesthetic, and surgical management have resulted in a reduction in the
      incidence of neurological injury in CABG patients over the past decade. On the
      other hand, an increasingly elderly population with more severe comorbidity, who
      are more prone to cerebral injury, are increasingly being referred for CABG.
      Possible mechanisms to reduce overt and subtle cerebral injury are discussed. The
      use of composite arterial grafts performed on the beating heart may be the most
      effective way of minimizing the risk of cerebral injury associated with CABG.

PMID- 11584165
TI  - Myocardial viability: recent developments in detection and clinical significance.
AB  - The long-term prognosis of patients with ischemic cardiomyopathy is highly
      variable, depending on the extent of myocardial viability and the success and
      completeness of the revascularization techniques used. Other important factors
      include left ventricular function, extent of coronary artery disease (CAD), and
      patient age. Chronic left ventricular dysfunction in ischemic cardiomyopathy is
      the result of a mixture of scarred as well as hibernating myocardium. In fact,
      most patients have both scarring and hibernation in different regions. Transmural
      biopsies of dysfunctional segments reveals that recovery of function is inversely
      proportional to the extent of fibrosis and that endocardial fibrosis extending
      over 30% of the myocardial thickness precludes recovery of function.Nagueh et al.
      [1] evaluated the relation of contractile reserve and thallium uptake in
      hibernating myocardium to myocardial structure in humans. The authors found that
      segments with postoperative functional recovery had more wall thickening at low
      dose dobutamine echocardiography (DE), higher thallium uptake, and less fibrosis
      (2.0 vs 28%) than those segments without recovery. Also, segments with viability
      on DE had less fibrosis, less vimentin and fibronectin, more glycogen, and higher
      thallium uptake, than those segments without viability. Importantly, segments
      viable by single-photon emission computed tomography (SPECT) and DE had
      significantly less fibrosis (1%) than those viable by only one of the two
      techniques. In this review, we discuss recent developments in the detection of
      myocardial viability, including echocardiography, nuclear cardiac imaging,
      magnetic resonance imaging (MRI), and other techniques.

PMID- 11584167
TI  - The thin-cap fibroatheroma: a type of vulnerable plaque: the major precursor
      lesion to acute coronary syndromes.
AB  - While the concept of plaque 'vulnerability' implies a propensity towards
      thrombosis, the term vulnerable was originally intended to provide a morphologic
      description consistent with plaques that are prone to rupture. It is now known
      that the etiology of coronary thrombi is diverse and can arise from entities of
      plaque erosion or calcified nodules. These findings have prompted the search for
      more definitive terminology to describe precursor lesions associated with
      rupture, now referred to as thin-cap fibroatheromas. This review focuses on the
      thin-cap fibroatheroma, as a specific cause of acute coronary syndromes. To put
      these issues into current perspective, we need to revisit some of the older
      literature describing plaque morphology in stable and unstable angina, acute
      myocardial infarction, and sudden coronary death. The morphology, frequency, and
      precise location of these thin-cap fibroatheromas are further discussed in
      detail. Potential mechanisms of fibrous cap thinning are also addressed, in
      particular emerging data, which suggests the role of cell death "apoptosis" in
      cap atrophy.

PMID- 11584168
TI  - Adjunctive pharmacotherapy for coronary stenting.
AB  - The use of coronary stents improves the outcomes of percutaneous coronary
      intervention (PCI). This has led to a rapid increase in their use. Coronary
      stenting is not without problems and is complicated by both early ischemic events
      and late restenosis. The combination of anticoagulation with unfractionated
      heparin (UFH) and the use of antiplatelet agents including aspirin,
      thienopyridines, and glycoprotein IIb/IIIa inhibitors has led to a major
      reduction in early ischemic events after stenting. Low molecular weight heparin
      (LMWH) and direct thrombin inhibitors have a number of theoretical advantages
      over UFH. Their role as an adjunct to coronary stenting is still under
      investigation. Trials of systemic pharmacotherapy aimed at reducing in-stent
      restenosis have been consistently disappointing. Preliminary results of stents
      coated with agents that inhibit neointimal proliferation are extremely promising.
      The results of ongoing phase III trials of these coated stents are eagerly
      awaited.

PMID- 11584169
TI  - The use of mechanical devices as adjuncts to intracoronary stenting.
AB  - A number of mechanical adjuncts to intracoronary stenting are now available to
      the interventional cardiologist. These devices have assisted in the development
      of a safer and more effective stenting practice. Intravascular ultrasound-guided
      stenting has been shown to reduce the rate of subacute thrombosis and subsequent
      restenosis. It allows a greater appreciation of lesion structure and severity so
      that an appropriate intervention strategy can be devised. Debulking techniques
      may allow the optimal deployment of stents so that restenosis is reduced;
      however, the results of large randomized studies are still awaited. The use of
      thrombectomy and distal embolization protection devices is emerging as a safer
      alternate to stenting alone in difficult patient subsets, such as those with
      thrombus-laden lesions and degenerated vein grafts. Doppler and pressure wires
      may be useful in determining optimal stent deployment and predict subsequent
      patient outcomes. An understanding of the indications and limitations of these
      devices is of increasing importance to the interventional cardiologist as the
      coming decade threatens to yield an impressive array of high-tech innovations.

PMID- 11584170
TI  - Minimally invasive CABG.
AB  - For more than three decades, conventional coronary artery bypass grafting (full
      sternotomy, cardiopulmonary bypass, and cardioplegic arrest) has been the
      treatment of choice for patients with multi-vessel coronary artery disease.
      However, neurologic injury secondary to ascending aortic manipulation and
      systemic inflammatory reaction related to cardiopulmonary bypass are major causes
      of morbidity. During the past decade research efforts have been focused on the
      development of innovative revascularization techniques to minimize these
      deleterious effects. Minimally invasive direct coronary artery bypass surgery was
      developed to reduce chest trauma and to accelerate patient recovery. The
      relatively recent introduction of mechanical stabilizers and positioning devices
      has allowed for the safe performance of off-pump coronary artery bypass for
      patients with multi-vessel disease. Robotic technology has offered the
      possibility of myocardial revascularization through limited access using
      endoscopic principles. Recently, emphasis has been placed on the development of
      new sutureless anastomotic devices that may revolutionize the field of myocardial
      revascularization and allow a broader acceptance of minimally invasive CABG.
      Despite the increasing availability of new technologies, the validity of these
      procedures must be evaluated carefully. Prospective randomized studies and
      longitudinal follow-up will be required.

PMID- 11584171
TI  - Transmyocardial laser revascularization.
AB  - Low-powered lasers were first used in the early 1980s to produce transventricular
      channels as an adjunct to coronary artery bypass graft surgery (CABG). Early
      results were encouraging, but because of the combined procedure, could not be
      attributed directly to use of the laser [1]. High-powered lasers were introduced
      into clinical practice in 1990 [2]. These lasers are powerful enough to create a
      transmyocardial channel with minimal thermal damage to surrounding tissues [3].
      Clinical studies, using transmyocardial laser revascularization (TMR) as the sole
      operative therapy for patients with severe and diffuse coronary artery disease
      (CAD) who have Class III or IV angina, and are on medical therapy, have been
      conducted since 1993. Based on the results of these studies, the FDA granted
      approval for the use of TMR as a sole therapy. Clinical studies are currently
      underway to assess the results of combined TMR and CABG [4]. Results of four
      controlled randomized studies have been published [5-8]. The data from two of
      these studies formed the basis for FDA approval of two different types of laser
      systems. The results of these studies have not provided any additional insights
      into the mechanism of action of TMR, which remains the Achilles' heel of this
      procedure. In this review, background information about the TMR procedure will be
      discussed along with an analysis of the recently published randomized studies.

PMID- 11584172
TI  - Listen to the patients: they will tell you the diagnosis.

PMID- 11584173
TI  - Bronchoalveolar lavage in interstitial lung disease.
AB  - Bronchoalveolar lavage (BAL) has become a standard diagnostic procedure for the
      majority of patients with interstitial disease. The technique is safe, minimally
      invasive, and reveals specific information in some disorders such as pulmonary
      alveolar proteinosis, Langerhans cell histiocytosis, alveolar hemorrhage,
      malignant infiltrates, or dust exposure. Here BAL can often replace lung biopsy.
      The results of BAL cell differentials with a lymphocytic, a neutrophilic, an
      eosinophilic, or a mixed cellular pattern can be used as an adjunct to diagnosis.
      If a BAL finding is compatible with the suspected diagnosis in the context of an
      appropriate disease history and clinical and radiologic findings, this can then
      be sufficient for disease confirmation. Recent research focused on the
      pathogenesis of various types of interstitial lung disorders. In this regard, BAL
      findings contributed to the characterization of idiopathic pulmonary fibrosis
      (IPF) as a condition with a predominant T-helper-2 (Th2) cytokine profile,
      whereas BAL findings in sarcoidosis and hypersensitivity pneumonitis are
      characterized by a Th1-dominant profile. The clinical value of BAL to assess the
      activity of disease processes and to provide prognostic information is still
      under debate. The routine performance of serial BAL is not recommended at
      present.

PMID- 11584174
TI  - Heterogeneity of pulmonary fibrosis: interstitial pneumonias and sarcoidosis.
AB  - This review focuses on two representatives of pulmonary fibrosis. One is usual
      interstitial pneumonia lesion, typically seen in patients with idiopathic
      pulmonary fibrosis. The other is parenchymal fibrosis along the bronchovascular
      bundles, observed in patients with sarcoidosis. Both are intractable fibrosis
      amenable only to lung transplantation. The authors trace the historical
      classification of idiopathic interstitial pneumonia, discuss interstitial
      pneumonia associated with collagen vascular diseases and occupational exposure,
      and review the most important issues to clarify both types of pulmonary fibrosis.

PMID- 11584175
TI  - Dust-induced interstitial lung disease in the tropics.
AB  - Inhalation of dusts is an important cause of interstitial lung disease in the
      tropical countries such as India. While dusts of organic origin, such as the
      cotton dust causing byssinosis, generally cause bronchial or bronchiolar
      involvement and hypersensitivity pneumonitis, inorganic metallic dusts cause
      progressive pulmonary fibrosis. Silicosis, coal workers' pneumoconiosis, and
      asbestosis are the three most commonly recognized forms of pneumoconiotic
      pulmonary fibrosis. Pulmonary tuberculosis is an important complication seen in
      up to 50% of patients of silicosis in some reports from India. The presentation
      is generally chronic, although acute and accelerated forms of silicosis are known
      when the exposures are heavy. Breathlessness, dry cough, and general
      constitutional symptoms are commonly seen. Patients with silicotuberculosis or
      other forms of infection may also have significant expectoration, hemoptysis,
      fever, and rapid progression. Respiratory failure and chronic cor pulmonale occur
      in the later stages. The diagnosis is easily established if the occupational
      history is available. Dense nodular opacities on chest roentgenograms, which may
      be large in patients with massive pulmonary fibrosis, are characteristic.
      Emphysematous changes generally appear in advanced stages or in patients who
      smoke. Bronchoalveolar lavage and/or lung biopsy may occasionally be required to
      establish or exclude other causes of interstitial lung disease. Treatment is
      largely palliative, although a variety of drugs including corticosteroids and
      procedures such as whole lung lavage have been tried. None of these methods has
      yet been found successful in the treatment. Preventive safety steps, including
      removal of the patient from the site of exposure, are the only effective
      strategies to control disease progression.

PMID- 11584176
TI  - Idiopathic pulmonary fibrosis and malignancy.
AB  - The reported frequency of lung cancer in the setting of diffuse pulmonary
      fibrosis varies greatly, depending on the country of origin and the type of
      study. Most recent reports regarding diffuse pulmonary fibrosis in general and
      idiopathic pulmonary fibrosis in particular and lung cancers come from Japan;
      only a few clinical studies of this issue are available from other countries of
      the world, including the United States. The reported frequency ranges from 4.8%
      in the United States to 48.2% in Japan. The most frequent type of cancer is
      adenocarcinoma. Risk factors may include cigarette smoking, exposure to metal
      dusts, onset of idiopathic pulmonary fibrosis at an older age, and male
      predominance. Possible pathologic mechanisms are summarized. Given the very poor
      prognosis of idiopathic pulmonary fibrosis itself, with a mean survival of only
      2.8 years, and that different diagnostic criteria were used in each study, it is
      likely that many of these studies are flawed because they evaluate lesions other
      than idiopathic pulmonary fibrosis. Thus, the frequency of lung cancer in
      idiopathic pulmonary fibrosis is still uncertain, and clearly requires follow-up
      of cohorts of clinically well-characterized patients, using standard diagnostic
      criteria for idiopathic pulmonary fibrosis. Finally, if the association between
      idiopathic pulmonary fibrosis and lung cancer is reconfirmed in these studies,
      the molecular and genetic mechanisms governing the development of lung cancer in
      this setting require additional study.

PMID- 11584177
TI  - Interstitial lung disease in systemic sclerosis.
AB  - Systemic sclerosis is a multisystem disorder of unknown etiology and involves
      organ systems such as the skin, peripheral vasculature, gastrointestinal tract,
      kidney, heart, and the lungs is observed quite frequently. In this review, we
      discuss the development of interstitial lung disease, one of the common pulmonary
      manifestations and a major cause of mortality and morbidity in this disorder. It
      is, however, under-recognized and diagnosed late in the course of the illness.
      Early use of pulmonary function tests followed by bronchoalveolar lavage in
      appropriate cases helps in early diagnosis. Recent studies emphasize the role of
      various profibrotic and inflammatory cytokines both locally in the lung and
      systemically in its pathogenesis. Treatment is helpful in arresting the
      progression if initiated early. Cyclophosphamide with or without corticosteroids
      given orally or as intravenous pulse may be helpful.

PMID- 11584178
TI  - Unusual systemic disorders associated with interstitial lung disease.
AB  - Interstitial lung disease often starts as a reaction to a causative insult or
      antigen, such as an inhaled environmental organic or inorganic dust and
      autoimmune mediated injury. When no underlying cause can be found, the
      inflammatory change in the gas exchanging parts of the lungs and associated
      fibrosis is called idiopathic pulmonary fibrosis (cryptogenic fibrosing
      alveolitis). The common causes of pulmonary fibrosis can be classified as
      granulomatosus, nongranulomatous, neoplastic, and iatrogenic. There are other
      multisystem disorders not included in this classification that are associated
      with interstitial lung disease. Amyloidosis, Behcet disease, Kikuchi disease, and
      Whipple disease are such multiorgan disorders that involve the lungs.

PMID- 11584179
TI  - Extrapulmonary presentation of sarcoidosis.
AB  - Sarcoidosis is a systemic disease that usually has a pulmonary presentation.
      Extrapulmonary presentation of the disease is often unrecognized because the
      clinical signs ( eg, peripheral lymph nodes) and more important symptoms ( eg,
      renal stones or uveitis) do not usually indicate systemic disease. In three
      different long-term studies of patients with sarcoidosis, 1.5% of the patients
      presented with uveitis, 11.7% presented with peripheral lymph nodes, and 3.6%
      presented with renal stones; a total of 16.6% of the patients had extrapulmonary
      presentation of sarcoidosis. Two of the three studies were retrospective. Many
      patients may have skin, parotid gland, spleen, liver, central nervous system,
      bone, or heart presentation; 16.6% is only the tip of an iceberg. A well
      conducted, prospective, long-term study could indicate that more than 30% of
      patients with sarcoidosis have extrapulmonary presentations of the disease.

PMID- 11584180
TI  - Corticosteroids in idiopathic pulmonary fibrosis.
AB  - Corticosteroids were the mainstay of therapy for idiopathic pulmonary fibrosis
      (IPF) for more than four decades, but their efficacy is unproven and toxicities
      are substantial. The course of IPF is characterized by progressive respiratory
      insufficiency, leading to death within 3 to 8 years from the onset of symptoms.
      Although a subset (10-20%) of patients survives more than 10 years, there is no
      evidence that any form of therapy alters the natural history of the disease.
      Nonetheless, given the poor prognosis, a trial of corticosteroids is often given.
      Because of the rarity of IPF, randomized, placebo-controlled therapeutic trials
      have not been done. Further, no studies have compared differing dosages or
      duration of corticosteroid in matched patients. Interpretation of therapy
      efficacy is obscured by several factors including heterogeneous patient
      populations, inclusion of patients with histologic entities other than usual
      interstitial pneumonia, lack of objective, validated endpoints, different
      criteria for "response." We review published data regarding corticosteroid
      therapy for IPF and present a rationale for stratifying therapy based on host,
      demographic, and clinical factors that influence prognosis as well as risk for
      corticosteroid complications.

PMID- 11584181
TI  - Nonsteroidal therapy for idiopathic pulmonary fibrosis.
AB  - The treatment of interstitial lung disease usually has consisted of
      corticosteroids with or without either azathioprine or cyclophosphamide. These
      drugs mainly target the neutrophil. Recently, the role of the Th2 lymphocyte
      leading to fibrosis has been demonstrated in animal models and preliminary human
      studies. This finding has led to interest in cytokine therapy with the interferon
      treatments, which reduce the Th2 response. Other new treatments have focused
      specifically on the fibroblast or oxygen free radicals. The range of treatment
      for interstitial lung diseases is increasing. Current clinical trials are in
      progress to confirm the pilot studies recently reported. The future therapy of
      interstitial lung disease probably will consist of multiple agents aimed at
      several aspects of the inflammatory reaction of interstitial lung disease.

PMID- 11584182
TI  - Lung transplantation in interstitial lung disease.
AB  - Interstitial lung disease is a heterogeneous group of illnesses, some of which
      may progress to a fibrosing stage and cause respiratory failure. For selected
      candidates, lung transplantation is the ultimate therapeutic option. We review
      data on lung transplantation for various interstitial lung diseases. We address
      indications, procedures, and outcomes for patients undergoing transplantation.
      Unique issues affecting morbidity, mortality, and recurrence of disease are
      discussed. We review the literature of transplantation for specific interstitial
      lung diseases and the outcomes of transplantation for interstitial lung diseases.
      Candidates with idiopathic pulmonary fibrosis experience high mortality on the
      waiting list, but derive significant survival benefit from lung transplantation.
      Recurrence is reported for several interstitial lung diseases after lung
      transplantation. Survival with lung transplantation for interstitial lung
      diseases is comparable with that attained in recipients with other indications.
      Lung transplantation is a well-tolerated, effective therapy for respiratory
      failure in interstitial lung disease.

PMID- 11584183
TI  - Pulmonary vascular disease.

PMID- 11584184
TI  - Thromboembolism in brain tumors.
AB  - Venous thromboembolism commonly affects patients receiving treatment for primary
      and secondary cerebral tumors. We review the recent literature on the molecular
      mechanisms underlying this hypercoagulable state and clinical studies of
      antithrombotic prophylaxis and therapy in this population. A computerized search
      of the MEDLINE database for articles from 1966 to the present day.
      Keywords/search terms used were glioma, astrocytoma, glioblastoma multiforme,
      cerebral tumor, primary brain tumour, secondary brain tumour, venous
      thromboembolism, thromboprophylaxis, heparin, warfarin, anticoagulants, and caval
      filters. Although neurological deficit has been identified as an independent risk
      factor for thrombosis it is also clear that malignant brain tumors induce changes
      in the makeup of circulating blood, making it more likely to clot. Concern for
      the perceived risk of perioperative intracranial bleeding with antithrombotic
      prophylaxis appears not to be justified by the available evidence. Prospective
      assessment of low molecular weight heparins for prophylaxis and treatment of
      established thrombosis is required. Antithrombotic therapy may also offer
      advantages over intracaval devices in prevention of secondary pulmonary embolism
      in patients with brain tumors.

PMID- 11584185
TI  - Prophylaxis of venous thromboembolism in medical patients.
AB  - Prophylaxis of venous thromboembolism in medical patients is an area where the
      potential benefits to patients are great. Venous thromboembolism is at least as
      common among medical as it is among surgical patients. Despite the widespread use
      of thromboprophylaxis in surgical patients, fatal pulmonary embolism is one of
      the most common causes of preventable death in the hospital. This may result from
      underuse of thromboprophylaxis in medical patients. The incidence of venous
      thromboembolism varies, but a history of previous venous thromboembolism, age 40
      years and older, immobility, and specific illnesses such as stroke, myocardial
      infarction, heart failure, and cancer put patients at particular risk. Most early
      studies assessed the use of anticoagulants such as unfractionated heparin, low
      molecular-weight heparin, and warfarin at reducing the incidence of venous
      thromboembolism in surgical patients. More recent studies and those currently
      being carried out are assessing the role of thromboprophylaxis in general medical
      patients and those with specific medical illnesses. As the evidence accumulates
      and guidelines are strengthened physicians will be able to tailor the use of
      thromboprophylaxis to the individual patient's needs.

PMID- 11584186
TI  - Prevention of venous thromboembolism in trauma and long bone fractures.
AB  - Patients sustaining traumatic injuries are at high risk for the development of
      venous thromboembolism. The reported incidence of deep venous thrombosis in
      trauma patients ranges from 20 to 90%. The reported incidence of pulmonary
      embolism in trauma patients varies between 2.3 and 22%. The aging population and
      the survival of more severely injured patients may suggest an increasing risk of
      thromboembolism in the trauma patient population. There have been few randomized
      prospective studies assessing methods of thromboembolism prophylaxis in trauma
      patients. Controversy exists as to the optimal method of prophylaxis in this high
      risk population. Contraindications arising from associated injuries often limit
      the potential options for prophylaxis in patients with trauma. Large prospective
      randomized studies are needed to determine the most effective means of
      prophylaxis in trauma patients, who have a wide range of both isolated and
      combined injuries. Future studies should also address the duration of prophylaxis
      because many trauma patients remain immobile for an extended time.

PMID- 11584187
TI  - Orally active heparin and low-molecular-weight heparin.
AB  - The heparins, (unfractionated heparin (UFH) and low-molecular-weight heparins
      (LMWH)) given by subcutaneous or intravenous injection have been used extensively
      in the prevention and treatment of both venous and arterial thromboembolic
      disorders. The increasing use of the heparins, LMWHs in particular, in the out of
      hospital setting has stimulated interest in the development of orally absorbable
      antithrombotic agents that require little or no monitoring, and this includes the
      heparins. UFH or LMWH delivered orally has been shown to have an antithrombotic
      effect in animal thrombosis models although there is little change in plasma
      coagulation tests. The addition of a simple organic chemical N -(8-(2
      hydroxybenzoyl)amino)caprylate (SNAC) to UFH markedly enhances its absorption. A
      phase II study in patients undergoing total hip replacement indicated that SNAC
      heparin in two different doses was as effective and safe as UFH given
      subcutaneously. A phase III clinical trial comparing two doses of SNAC heparin
      given orally with LMWH by subcutaneous injection for the prevention of venous
      thromboembolism in patients undergoing total hip replacement is currently
      underway.

PMID- 11584188
TI  - New methods for estimating pretest probability in the diagnosis of pulmonary
      embolism.
AB  - The clinical assessment of the probability of pulmonary embolism is a key step in
      proposed diagnostic strategies for pulmonary embolism, because the interpretation
      of noninvasive test results is conditional on the pretest probability derived
      from the presence or absence of clinical factors. The past year has brought
      important progress in the general area of clinical prediction of pulmonary
      embolism with the publication of two new simple clinical prediction rules. Each
      of the prediction rules includes a total of seven clinical variables that, when
      combined, allow for the categorization of patients into categories of low,
      intermediate, or high pretest probability of pulmonary embolism. Although these
      clinical prediction rules are perhaps only slightly better than the estimates of
      experienced clinicians, they provide an explicit method for estimating the
      probability of PE as an adjunct to diagnostic testing. Further validation work is
      now needed to assess how well these new prediction rules perform in settings
      other than the derivation sites.

PMID- 11584189
TI  - Prognosis in pulmonary embolism.
AB  - Acute pulmonary embolism has a wide prognostic spectrum, ranging from sudden
      death within minutes of a thromboembolic episode to a benign treatable condition
      associated with a stable clinical course and no long-term sequelae. In patients
      who survive an initial thromboembolic episode and receive antithrombotic therapy,
      the clinical course can be complicated by recurrent nonfatal venous
      thromboembolism, fatal pulmonary embolism, the postthrombotic syndrome, and
      chronic thromboembolic pulmonary hypertension. Identifying which patients are at
      increased risk of experiencing these sequelae is important in decision making
      relating to the aggressiveness of initial antithrombotic therapy, the duration of
      antithrombotic therapy, and the frequency of clinical surveillance. In addition,
      this information may be helpful to clinicians in discussing disease prognosis
      with patients. The objectives of this review are to provide reasonable estimates
      of the risks of recurrent nonfatal venous thromboembolism, fatal pulmonary
      embolism, the postthrombotic syndrome, and chronic thromboembolic pulmonary
      hypertension in patients with treated pulmonary embolism, and to identify risk
      factors for these sequelae.

PMID- 11584190
TI  - Outpatient treatment of patients with deep-vein thrombosis or pulmonary embolism.
AB  - There have been a large number of randomized trials comparing standard
      unfractionated intravenous heparin with low-molecular-weight heparin for the
      treatment of deep-vein thrombosis, but only two of these have looked at
      outpatient therapy. There have been only two randomized trials including patients
      with symptomatic pulmonary embolism, and neither of these provided outpatient
      therapy. Postmortem and clinical studies have shown a strong association between
      pulmonary embolism and the presence of venous thrombosis in the lower limbs.
      Based on similar rates of venous thromboembolic recurrence and death, these
      studies suggest that initial treatment should be the same for deep-vein
      thrombosis and pulmonary embolism. The feasibility of providing outpatient care
      to many patients seeking treatment for deep-vein thrombosis or acute pulmonary
      embolism at certain tertiary care hospitals has become evident, but the data
      suggest that the proportion of eligible patients is institution dependent and may
      vary from 18% to 91%. In the author's institution, approximately 50% of patients
      with pulmonary embolism could be treated as outpatients, but there have been no
      other reports on outpatient therapy for patients with pulmonary embolism. If
      patients with pulmonary embolism meet criteria demonstrated to result in a higher
      risk of death, it is, of course, reasonable to not treat such patients on an
      outpatient basis. Low-molecular-weight heparin followed by oral anticoagulant
      therapy provides adequate therapy in most patients with deep-vein thrombosis or
      pulmonary embolism, and many patients can be treated as outpatients.

PMID- 11584191
TI  - Anticoagulation in the elderly.
AB  - Oral anticoagulation therapy has demonstrated benefit in the treatment and
      prevention of a variety of thromboembolic disorders. Most individuals who receive
      oral anticoagulant therapy are elderly patients with nonvalvular atrial
      fibrillation and acute or recurrent venous thromboembolism. Anticoagulation in
      elderly patients poses unique challenges for the practicing clinician because
      they are simultaneously at higher risk for recurrent thromboembolism and major
      bleeding, including catastrophic intracranial hemorrhage. The pharmacology of
      warfarin in the elderly is reviewed, including important drug interactions and
      current dosing recommendations for elderly patients. Evidence of the benefits and
      risks of oral anticoagulation therapy are reviewed for patients with atrial
      fibrillation and venous thromboembolism. This information should enable
      practitioners to better assess the relative risks and benefit of oral
      anticoagulation therapy to guide treatment decisions in the elderly.

PMID- 11584192
TI  - The concept and application of antisense oligonucleotides.
AB  - Since the identification of the double-stranded DNA helix by Watson and Crick in
      1953, the knowledge of nucleotide structure and function has been an important
      potential tool in the study and therapy of disease. There is recent clinical
      evidence that antisense oligonucleotides may be important therapeutic compounds
      in the clinical therapy of a range of diseases, including infection (viruses and
      bacteria), oncology, and inflammation. Our laboratory-based understanding of
      antisense oligonucleotide activity has provided a foundation for their use in
      several human diseases. Potentially relevant applications include inflammatory
      bowel disease therapy, psoriasis, transplantation, rheumatoid arthritis,
      cytomegalovirus retinitis, hepatitis C, and solid tumor therapy. Here we will
      outline these applications as well as our ongoing clinical trials for Crohn's
      disease.

PMID- 11584193
TI  - Anal sphincter injury after vaginal delivery in primiparous females.
AB  - PURPOSE: The purpose of this study was to determine the incidence of anal
      sphincter injury and fecal incontinence after vaginal delivery. METHODS: This was
      a prospective, descriptive, observational study conducted over a three-year
      period in healthy primiparous females with previously intact anal sphincter and
      normal continence and without history of anorectal surgery. All patients
      completed a continence questionnaire and underwent endoanal ultrasound four to
      six weeks before and six weeks after delivery. RESULTS: Ninety-eight primiparous
      females had either instrumental (vacuum or forceps) vaginal delivery (n = 23) or
      noninstrumental vaginal delivery (n = 75). Twenty patients, 11 (48 percent) after
      instrumental delivery and 9 (12 percent) after noninstrumental vaginal delivery,
      had clinical sphincter tears that required primary repair. Twenty-eight patients
      (29 percent), 19 with previously repaired sphincter injury, had ultrasonographic
      defects that involved the external sphincter (n = 19) or both the internal and
      external sphincter (n = 9). Twenty-one patients (75 percent) with
      ultrasonographic sphincter defects had either major (n = 5) or minor (n = 16)
      fecal incontinence. CONCLUSION: Anal sphincter injuries, many of them undiagnosed
      at the time of delivery, are common in primiparous females after vaginal
      delivery, especially if vacuum or forceps are used. These injuries cause fecal
      incontinence in a significant proportion of the patients. Patients undergoing
      vaginal delivery should be aware of the risks of anal sphincter injury.

PMID- 11584194
TI  - Predicting polyposis severity by proctoscopy: how reliable is it?
AB  - PURPOSE: Patients with familial adenomatous polyposis need prophylactic colectomy
      and ileorectal anastomosis or restorative proctocolectomy. Preoperative rectal
      polyp counts have been used as one factor to determine which operation should be
      done, triaging patients according to risk of rectal cancer or completion
      proctectomy after ileorectal anastomosis. This study was designed to examine the
      reliability of preoperative proctoscopy in predicting familial adenomatous
      polyposis severity and outcome after ileorectal anastomosis. METHODS: Familial
      adenomatous polyposis patients were categorized according to preoperative
      proctoscopy as follows: Group 1, 5 or fewer adenomas; Group 2, 6 to 19 adenomas;
      Group 3, 20 or more adenomas. Familial adenomatous polyposis severity was defined
      as mild if there were < 1,000 polyps in the colon at colectomy and severe if
      there were > 1,000 polyps. RESULTS: A total of 213 patients were reviewed, 80 in
      Group 1, 59 in Group 2, and 74 in Group 3. There was no difference among the
      groups in mean age at presentation. Patients with fewer than five rectal adenomas
      were predominately females. They rarely had symptoms (22.8 percent), had mostly
      mild polyposis (86.5 percent), and in 74 of 80 cases underwent ileorectal
      anastomosis. Only six underwent restorative proctocolectomy. Of those having an
      ileorectal anastomosis, five needed later proctectomy, none for cancer. Patients
      with 6 to 19 rectal polyps were a similar group to those with 5 or fewer. Most
      were asymptomatic (67.8 percent), most had mild polyposis (81.6 percent), and 54
      of 59 underwent ileorectal anastomosis (5 had restorative proctocolectomy). Only
      3 of the 54 having ileorectal anastomosis needed subsequent proctectomy, 2 for
      rectal cancer. The patients with 20 or more rectal polyps were different. They
      usually presented with symptoms (86 percent), the majority (56.6 percent) had
      severe polyposis, and only 50 percent (37/74) underwent ileorectal anastomosis,
      the other half having restorative proctocolectomy. Of the 37 patients with an
      ileorectal anastomosis, 13 needed later proctectomy (35.1 percent), 4 for cancer
      (10.8 percent). CONCLUSION: Fewer than five rectal adenomas at presentation
      almost always predicts mild disease, and patients do well after ileorectal
      anastomosis. Twenty or more adenomas usually means severe disease. Patients with
      6 to 19 adenomas are often mildly affected, but their phenotype is less benign
      than that of patients with fewer than five polyps. Although not foolproof,
      proctoscopy is a useful test in triaging patients with familial adenomatous
      polyposis according to disease severity.

PMID- 11584195
TI  - Clinical rather than laboratory assessment predicts continence after anterior
      sphincteroplasty.
AB  - PURPOSE: Preoperative anorectal physiology studies have become part of the
      standard evaluation of fecal incontinence. This study was undertaken to see
      whether anorectal physiology results predicted surgical outcome after anterior
      sphincteroplasty. METHODS: Between 1985 and 1994, 191 females with a mean age of
      37 (range, 20-74) years underwent anterior sphincteroplasty for anal sphincter
      disruption. A follow-up questionnaire was sent to all patients, and there were
      158 respondents (83 percent). Mean follow-up was 43 (range, 6-120) months.
      Obstetric injuries accounted for incontinence in 91 percent of the 158 patients
      who responded to the questionnaire. Mean duration of incontinence was 4.2 years
      (range, 3 months-51 years) before surgery. Preoperatively, patients were
      incontinent to solid stool (53 percent), liquid stool (33 percent), gas (3
      percent), and unspecified (11 percent). RESULTS: Subjectively, the results were
      as follows: 129 patients (82 percent) improved, 17 (11 percent) were initially
      improved but subsequently deteriorated, 7 (4 percent) were unchanged, and 5 (3
      percent) were worse. Objectively, postoperative continence was classified as
      follows: excellent (normal) in 23 percent, good (incontinent to gas or minor
      stain) in 39 percent, fair (incontinent to stool an average of less than once per
      month) in 26 percent, and poor (incontinent to stool an average of greater than
      once per month) in 12 percent. Preoperative continence level (incontinent to
      solid vs. liquid stool) was predictive of postoperative continence
      classification. Preoperative anorectal manometry was not predictive of clinical
      outcome (n = 128). There was no significant difference in postoperative
      continence classification among patients with normal, unilaterally abnormal, and
      bilaterally abnormal pudendal latency (n = 89). CONCLUSIONS: Clinical rather than
      manometric assessment predicts continence after anterior sphincteroplasty.

PMID- 11584196
TI  - Short-term sacral nerve stimulation for functional anorectal and urinary
      disturbances: results in 40 patients: evaluation of a new option for anorectal
      functional disorders.
AB  - PURPOSE: There are several options in the treatment of fecal incontinence; it is
      often difficult to choose the most appropriate, adequate treatment. The
      consolidated experience gained in the urologic field suggests that sacral nerve
      stimulation may be a further option in the choice of treatment. The aim of our
      study was to evaluate the preliminary results of the peripheral nerve evaluation
      test obtained in a multicenter collaborative study on patients with defecatory
      and urinary disturbances. METHODS: Forty patients (9 males; mean age, 50.2;
      range, 26-79 years) underwent the peripheral nerve evaluation test, 28 (70
      percent) for fecal incontinence and 12 (30 percent) for chronic constipation.
      Fourteen (35 percent) patients also had urinary incontinence; six had urge
      incontinence, two had stress incontinence, and six had retention incontinence.
      Associated diseases were scleroderma (2 patients), spinal injuries (4 patients),
      and syringomyelia (1 patient). All the patients underwent preliminary
      investigations with anorectal manometry, pudendal nerve terminal motor latency
      testing, anal ultrasound, defecography, and if required, urodynamic tests. The
      electrode for sacral nerve stimulation was positioned percutaneously under local
      anesthesia in the S2 (4), S3 (34), or S4 (1) foramen unilaterally (1 patient not
      accounted for because of no response to acute test), based on the best motor and
      subjective responses of paresthesia of the pelvic floor. Stimulation parameters
      were average amplitude, 2.8 (range, 1-6) V and average frequency, 15 to 25 Hz.
      RESULTS: The mean duration of the tests was 9.9 (range, 7-30) days; tests lasting
      fewer than seven days were not evaluated. There were four early displacements of
      the electrode. In 22 of the 25 evaluable patients with fecal incontinence, there
      was an improvement of symptoms (88 percent), and 11 (44 percent) were completely
      continent to liquid or solid stools, whereas in 7 symptoms were unchanged. Mean
      number of episodes of liquid or solid stool incontinence per week was 8.1 (range,
      4-18) in the prestimulation period and 1.7 (range, 0-12) during the peripheral
      nerve evaluation test. (P = 0.001; Wilcoxon's signed-rank test). The most
      important manometric findings were: increase of maximum rest pressure (39.4 +/-
      7.3 vs. 54.3 +/- 8.5 mmHg; P = 0.014, Wilcoxon's test) and maximum squeeze
      pressure (84.7 +/- 8.8 vs. 99.5 +/- 1.1 mmHg; P = 0.047), reduction of initial
      threshold (63.6 +/- 5.2 vs. 42.4 +/- 4.7 ml; P = 0.041) and urge sensation (123.8
      +/- 0.6 vs. 78.3 +/- 8.9 ml; P = 0.05). An improvement was also found in patients
      with constipation, with reduction in difficulty emptying the rectum, with
      prestimulation at 7 (range, 2-21) episodes per week and end of peripheral nerve
      evaluation test at 2.1 (range, 0-6) episodes per week, P < 0.01) and in the
      number of unsuccessful visits to the toilet, which dropped from 29.2 (7-24) to
      6.7 (0-28) per week (P = 0.01). The most important manometric findings in
      constipated patients were an increase in amplitude of maximum squeeze pressure
      during sacral nerve stimulation (prestimulation, 63 +/- 0 mm Hg; end of
      peripheral nerve evaluation test, 78 +/- 1 mm Hg; P = 0.009) and a reduction in
      rectal volume for urge threshold (prestimulation, 189 +/- 52 ml; end of
      peripheral nerve evaluation test, 139 +/- 45 ml; P = 0.004). CONCLUSIONS: In
      functional bowel disorders short-term sacral nerve stimulation seems to be a
      useful diagnostic tool to assess patients for a minor invasive therapy
      alternative to conventional surgical procedure.

PMID- 11584198
TI  - Extended follow-up of patients treated with cytotoxic chemotherapy for intra
      abdominal desmoid tumors.
AB  - BACKGROUND: Cytotoxic chemotherapy can achieve a good initial response in
      inoperable desmoid tumors that have caused progressive obstruction of the
      gastrointestinal and urinary tracts and have caused unrelenting pain. METHODS: We
      have reviewed 8 patients (3 male) with desmoid tumors and familial adenomatous
      polyposis who underwent cytotoxic chemotherapy for inoperable gastrointestinal
      obstruction and/or uncontrolled pain. They were treated with doxorubicin and
      dacarbazine followed by carboplatin and dacarbazine. RESULTS: Follow-up after
      cytotoxic chemotherapy in the 7 patients for whom it was available was a mean of
      42 (range 24-54) months. Two patients achieved complete remission after therapy.
      Four patients achieved a partial remission after completing all or some of the
      chemotherapy regimen; of these, three remained in stable remission, whereas the
      other was lost to follow-up. There were two recurrences that required further
      therapy; one of these patients was treated with further chemotherapy, which
      induced a second remission, and the other was treated with pelvic exenteration
      and has subsequently died. CONCLUSIONS: Most patients had a substantial response
      to cytotoxic chemotherapy; however, two patients required additional therapy 24
      and 30 months after cytotoxic chemotherapy, respectively. Cytotoxic chemotherapy
      is effective in producing short-term and long-term remission in these difficult
      patients.

PMID- 11584199
TI  - Randomized, controlled trial of lateral node dissection vs. nerve-preserving
      resection in patients with rectal cancer after preoperative radiotherapy.
AB  - PURPOSE: The effectiveness of preoperative radiation therapy for advanced lower
      rectal carcinoma to preserve the function of pelvic organs and reduce local
      recurrences was examined in a prospective, randomized, controlled study. METHODS:
      Fifty-one patients with a diagnosis of localized and resectable adenocarcinoma of
      the lower rectum undergoing 50 Gy of preoperative radiotherapy were recruited
      into the trial between April 1993 and March 1995. The patients were randomly
      allocated to complete autonomic nerve-preserving surgery without lateral node
      dissection (D1), or surgery with dissection of the lateral lymph nodes including
      autonomic nerves (D2) followed by oral administration of carmofur for one year.
      RESULTS: No difference was observed in either survival or disease-free survival
      between D1 and D2 groups. There was no difference between the two groups in terms
      of recurrence rate. A significant difference was observed in urinary and sexual
      function (P = 0.02 and 0.02, respectively) one year after surgery between D1 and
      D2 groups. CONCLUSION: This study suggests that lateral node dissection is not
      necessary in terms of curability for patients with advanced carcinoma of the
      lower rectum who undergo preoperative radiotherapy.

PMID- 11584201
TI  - Evaluation of Bethesda guidelines in relation to microsatellite instability.
AB  - PURPOSE: The Bethesda guidelines were developed for selection of patients whose
      tumors should be tested for high microsatellite instability. This study examined
      the validity of the different Bethesda criteria in relation to microsatellite
      instability status to simplify their use in clinical practice. METHODS: A total
      of 164 patients with colorectal or hereditary nonpolyposis colorectal cancer
      associated cancers were registered on the basis of the Amsterdam criteria without
      age limitations (11 cases), multiple tumors (2 cases), the accumulation of
      colorectal cancer in the family (no first-degree relatives affected or the index
      patient's age up to 50 years; 45 cases), an early age at onset up to 50 years (13
      cases), morphologic and histopathologic manifestations (right-sided colorectal
      cancer, mucinous undifferentiated histology; 1 case), and the Bethesda criteria
      (92 cases). The microsatellite instability status of tumors was determined using
      the International Collaborative Group on Hereditary Non-Polyposis Colorectal
      Cancer marker reference panel. RESULTS: When applying all Bethesda criteria, high
      microsatellite instability tumors were identified in our hereditary nonpolyposis
      colorectal cancer registry with a sensitivity of 87 percent. Twenty-nine percent
      (27/92) of the Bethesda-positive patients displayed high microsatellite
      instability compared with 6 percent of patients (4/72) not meeting these criteria
      (P < 0.001). Only Bethesda Criteria 1, 3, and 4 showed a significantly different
      distribution of the microsatellite instability status when compared with those of
      the remaining patients registered (P < or = 0.001). These three criteria detected
      high microsatellite instability tumors in 48 percent (10/21), 50 percent (18/36),
      and 31 percent (21/67) of patients, respectively. When applying these criteria
      only, a cumulative detection rate of 77 percent of all (24/31) high
      microsatellite instability cases was found, thereby identifying 89 percent of
      high microsatellite instability tumors among the Bethesda-positive patients.
      Patients matching Criteria 1, 3, and 4 frequently showed hMSH2 or hMLH1 germline
      mutations and tumor-specific loss of protein expression. CONCLUSION: In our
      hereditary nonpolyposis colorectal cancer registry the complete Bethesda criteria
      showed the highest sensitivity to identify patients with high microsatellite
      instability tumors. However, for general medical practice outside academic
      centers, three criteria are reasonably accurate for adequate high microsatellite
      instability tumor selection.

PMID- 11584202
TI  - Tissue inhibitor of metalloproteinase-3 is a basement membrane-associated protein
      that is significantly decreased in human colorectal cancer.
AB  - PURPOSE: The balance between local levels of matrix metalloproteinases and tissue
      inhibitor of metalloproteinases is believed to play a key role in tumor invasion
      and metastases. Because tissue inhibitor of metalloproteinase-3 suppresses
      tumorigenicity and tumor invasion in vitro, the aim of this study was to
      determine its expression in human colorectal cancer. METHODS: Thirty-nine human
      colorectal cancer specimens, three adenomas, and matched normal adjacent mucosa
      from 39 colorectal cancer patients were analyzed. Tissue inhibitor of
      metalloproteinase-3 ribonucleic acid and protein expression were analyzed by
      Northern blot hybridization and Western blot analysis, respectively. The cellular
      localizations of tissue inhibitor of metalloproteinase-3 ribonucleic acid and
      protein were determined by in situ hybridization and immunolocalization. RESULTS:
      Tissue inhibitor of metalloproteinase-3 ribonucleic acid expression was increased
      in colorectal cancer compared with paired normal mucosa. In contrast, tissue
      inhibitor of metalloproteinase-3 protein level was higher in normal mucosa than
      in the corresponding colorectal cancer. In addition, tissue inhibitor of
      metalloproteinase-3 protein levels progressively decreased with advancing
      colorectal cancer stages. Tissue inhibitor of metalloproteinase-3 protein tumor
      to normal mucosa ratio was 0.74 +/- 0.12, 0.51 +/- 0.18, 0.48 +/- 0.12, and 0.45
      +/- 0.2 for Dukes A (n = 8), B (n = 9), C (n = 9), and D (n = 13) stages,
      respectively. Both tissue inhibitor of metalloproteinase-3 messenger ribonucleic
      acid and protein were located predominantly within spindle-shaped and round
      stromal cells. Furthermore, in colonic epithelium, tissue inhibitor of
      metalloproteinase-3 and type IV collagen protein were similarly concentrated in
      the basal region. CONCLUSIONS: These data provide the first detailed description
      of the cellular expression of tissue inhibitor of metalloproteinase-3 in
      colorectal cancer and identify it as a basement membrane-associated protein. This
      is an important observation, because the presence of tissue inhibitor of
      metalloproteinase-3 protein near the basement membrane supports its role in
      preventing proteolytic degradation, angiogenesis, and apoptosis.

PMID- 11584203
TI  - CO2 pneumoperitoneum does not enhance tumor growth and metastasis: study of a rat
      cecal wall inoculation model.
AB  - INTRODUCTION: Although many studies have evaluated the effects of carbon dioxide
      pneumoperitoneum on port site recurrence, little is known about its outcome on
      tumor growth and metastasis. The effect of pneumoperitoneum with carbon dioxide
      on cecal tumor growth and metastasis was compared with laparotomy using a rat
      colon cancer cell line. METHODS: Time Course Study: Fifty WF/BN F1 hybrid rats
      were inoculated with 2,000,000 WB2054M5 tumor cells into the cecal wall and
      explored two to ten weeks after injection. Main Study: 152 rats were randomly
      assigned either to 6-mmHg CO2 pneumoperitoneum (30 minutes) or 4-cm laparotomy
      (30 minutes) two weeks after tumor inoculation and were explored four weeks after
      treatment. RESULTS: Time Course Study: Thirty-seven (95 percent) of the surviving
      rats developed a cecal wall tumor, and there was progressive tumor growth and
      metastasis over the ten-week period. At six weeks, metastasis occurred to the
      liver in 25 percent, to the lung in 38 percent, and to the lymph node in 63
      percent, and peritoneal seeding occurred in 38 percent; this time period was
      chosen for the main study. Main Study: At the time of treatment (2 weeks), 124
      rats were eligible for randomization. One hundred two rats survived the six-week
      period (50 pneumoperitoneum, 52 laparotomy) and were killed. There were no
      differences between the CO2 pneumoperitoneum and laparotomy groups regarding
      cecal tumor growth (1.043 vs. 0.894 g) and metastases to the liver (32 vs. 37
      percent), lung (34 vs. 17 percent), lymph node (84 vs. 77 percent), and wound or
      port (20 vs. 23 percent). CONCLUSIONS: A cecal wall inoculation model mimics the
      natural cascade of colon cancer growth and metastasis. CO2 pneumoperitoneum did
      not affect the tumor growth and metastasis to the liver and other organs when
      compared with laparotomy in this model.

PMID- 11584204
TI  - Source of errors in the evaluation of early rectal cancer by endoluminal
      ultrasonography.
AB  - PURPOSE: Although preoperative evaluation of early rectal cancers can be done by
      endoluminal sonography and by means of colonoscopic findings, it is still
      controversial whether endoluminal sonography can effectively discriminate mucosal
      from submucosal lesions. This study was performed to verify objective causes of
      errors in the evaluation of early rectal cancer (T0/1) using a review of
      videotaped endoluminal sonography images. METHODS: Eighty-nine patients with
      suspected early rectal cancer on endoluminal sonography were included. Two
      different scanners with appropriate probes were used according to tumor location,
      i.e., transrectal ultrasonography was used to scan up to 8 cm of the rectum above
      the anal verge, whereas endoscopic ultrasonography was used to assess higher
      lesions. Endoluminal sonography images were correlated with histologic
      infiltration and were reevaluated carefully to identify sources of errors.
      RESULTS: Sensitivity and specificity were 83.1 and 96.5 percent, respectively,
      for tumor staging, whereas sensitivity was very low compared with specificity
      (16.7 vs. 90.2 percent) for metastatic lymph nodes. Endoluminal sonography images
      showed irregularity of the underlying tumor border (P < 0.01) and hypoechoic
      blurring or cutoff of the inner and outer hypoechoic layers (P < 0.001), all of
      which closely correlated with histologic infiltration of tumor cells. Overstaging
      occurred more than twice as often as understaging in tumor reevaluation (14 vs. 5
      occurrences). In contrast to tumors, lymph nodes showed a similar amount of both
      overstaging (four cases) and understaging (five cases). The sources of errors
      were summarized as five types: false instrumentation, interpretive errors,
      anatomic defects, imaging failure, and inevitable errors. CONCLUSIONS: Because
      false instrumentation, interpretive errors, and anatomic defects were considered
      preventable, 23 (82.1 percent) of the 28 errors might have been avoided.
      Therefore, a clear image by endoluminal sonography can effectively distinguish
      mucosal from submucosal lesions in early rectal cancer.

PMID- 11584205
TI  - Reoperative abdominal and perineal surgery in ileoanal pouch patients.
AB  - PURPOSE: Complications of the ileal pouch with ileoanal anastomosis are
      associated with poor function and diminished quality of life; often, these
      complications may require surgery to salvage the pouch. The aims of this study
      were to review our experience with reoperative ileoanal pouch surgery and to
      define any predictors of pouch salvage surgery. METHODS: Between 1991 and 1999,
      the medical records of all patients who underwent reoperative ileoanal pouch
      surgery for either pouch salvage or pouch excision were reviewed; any minor local
      procedures were excluded. Successful ileoanal pouch salvage was considered to be
      an intact and functioning pouch, with acceptable patient satisfaction and good
      control. RESULTS: Thirty-two patients underwent reoperative ileoanal pouch
      surgery, 25 for attempted pouch salvage and 10 for pouch excision (3 patients
      were included in both groups). Five patients (20 percent) had pouch
      reconstruction, 1 of which was successful; 8 (32 percent) had pouch advancement,
      with a 62 percent success rate; and 16 (64 percent) had local perianal procedures
      for control of perianal sepsis, with a 75 percent success rate (4 of these
      required further surgery). The overall success rate of ileoanal pouch salvage
      surgery was 84 percent, with 64 percent of patients having acceptable function.
      There was no correlation between the number of ileoanal pouch salvage procedures
      and failure. Four (40 percent) of the 10 patients who had pouch excision were
      ultimately diagnosed with Crohn's disease. CONCLUSIONS: Ileoanal pouch salvage
      surgery is often successful and, in motivated patients without Crohn's disease,
      is worthwhile. Pouch advancement or local perianal repair yielded better results
      than did pouch reconstruction. Patients diagnosed with Crohn's disease after
      ileoanal pouch construction may be best suited for pouch excision when
      complications occur.

PMID- 11584207
TI  - Atypical diverticular disease: surgical results.
AB  - PURPOSE: Patients with diverticular disease may present with chronic symptoms but
      never develop diverticulitis. The purpose of this research was to review the
      outcome of surgical intervention in this subgroup of patients with atypical
      "smoldering" diverticular disease. METHODS: Records of 930 patients who underwent
      sigmoid resection for diverticular disease during a ten-year period at the Mayo
      Clinic in Rochester, Minnesota, were reviewed. Forty-seven patients (5 percent)
      fit our inclusion criteria for smoldering diverticular disease and underwent
      sigmoid colectomy with primary anastomosis. A minimum of 12 months of follow-up
      was completed in 68 percent of these patients. RESULTS: Evidence of acute or
      chronic inflammatory changes was present in 76 percent of resected specimens.
      Complete resolution of symptoms occurred in 76.5 percent, with 88 percent being
      pain free. CONCLUSIONS: We conclude that the diagnosis and presentation of
      atypical smoldering diverticular disease is an uncommon and poorly defined
      entity. However, sigmoid resection in this subgroup of patients is safe and is
      associated with resolution of symptoms in the majority of cases.

PMID- 11584208
TI  - Cyclooxygenase-2 is overexpressed in serrated adenoma of the colorectum.
AB  - PURPOSE: The aim of this study was to clarify whether cyclooxygenase-2 and
      cyclooxygenase-1 is expressed in hyperplastic polyps and serrated adenomas.
      METHODS: Forty-nine serrated adenomas and 25 hyperplastic polyps were
      immunostained using anticyclooxygenase-2 and anticyclooxygenase-1 antibodies.
      Cyclooxygenase-2 and cyclooxygenase-1 expression was investigated in all
      specimens. RESULTS: Cyclooxygenase-2 was expressed in dysplastic glands in the
      majority of serrated adenomas. Thirty-five of 49 (71.4 percent) serrated adenomas
      exhibited moderate to intense cyclooxygenase-2 immunoreactivity, and 8 of 25
      hyperplastic polyps (32 percent) showed weak to moderate cyclooxygenase-2
      immunoreactivity. Cyclooxygenase-1 immunoreactivity was very weak in all the
      hyperplastic polyps and serrated adenomas. CONCLUSIONS: These results suggest
      that cyclooxygenase-2 is overexpressed in serrated adenoma of the colorectum.
      Cyclooxygenase-2 inhibitors will reduce the incidence of serrated adenomas.

PMID- 11584209
TI  - Chemical colostomy irrigation with glyceryl trinitrate solution.
AB  - PURPOSE: Colostomy irrigation may improve patient quality of life, but is time
      consuming. This study tests the hypothesis that irrigation with glyceryl
      trinitrate solution, by inducing gastrointestinal smooth muscle relaxation, may
      accelerate expulsion of stool by passive emptying, thereby reducing irrigation
      time. METHODS: Fifteen colostomy irrigators(with more than 3 years' experience)
      performed washout with tap water compared with water containing 0.025 mg/kg
      glyceryl trinitrate. Fluid inflow time, total washout time, and hemodynamic
      changes occurring during glyceryl trinitrate irrigation were documented by an
      independent observer. Subjects recorded episodes of fecal leakage and overall
      satisfaction on a visual analog scale. Cramps, headaches, and whether or not a
      stoma bag was used were expressed as a percentage of number of irrigations.
      Comparison of fluid inflow time, total washout time, leakage, and satisfaction
      was by Wilcoxon's signed-rank test and headaches, cramps, and stoma bag use was
      by McNemar's test. Pulse rate (paired t-test), systolic and diastolic blood
      pressures (Wilcoxon's test) at 20 and 240 minutes after washout with glyceryl
      trinitrate solution were compared with baseline. RESULTS: Fifteen patients (9
      female), with a mean age of 53 (31-73) years, provided 30 sessions (15 with water
      and 15 with glyceryl trinitrate). Medians (interquartile ranges) for water vs.
      glyceryl trinitrate were fluid inflow time 7 (4-10) vs. 4, (3-5; P = 0.001);
      total washout time 40 (30-55) vs. 21, (15-24; P < 0.001); leakage 0 (0-1) vs. 0,
      (0-0; P = 0.02), satisfaction 10 (8-10) vs. 10 (9-10; P = 0.31). The number
      (percentage) of stoma bags, cramps, and headaches with water vs. glyceryl
      trinitrate were 7 (47 percent) vs. 7 (47 percent), P = 1; 1 (7 percent) vs. 14
      (93 percent), P < 0.001; and 0(0 percent) vs. 14 (93 percent), P < 0.001,
      respectively. Changes in pulse (increase) and systolic and diastolic blood
      pressures (decrease) from baseline were maximal at 20 minutes (P < 0.001, P =
      0.001, and P = 0.002, respectively) and had returned to baseline by 240 minutes
      (P = 0.52, P = 0.08, and P = 1, respectively). CONCLUSION: Glyceryl trinitrate
      solution significantly reduces colostomy irrigation time compared with the
      generally recommended tap water. Patients suffer fewer leakages and are highly
      satisfied, but side effects are potential drawbacks. Other colonoplegic agent
      solutions should now be evaluated.

PMID- 11584210
TI  - Circadian rhythm of rectal motor complexes.
AB  - PURPOSE: Prolonged rectal pressure recordings have revealed that the rectum
      exhibits typical bursts of regular pressure waves, also called rectal motor
      complexes. Although there is consensus regarding the characteristics of rectal
      motor complexes, their function is poorly understood. Furthermore, data regarding
      the circadian rhythm of these complexes are either lacking or conflicting.
      Therefore, we conducted a study to investigate the circadian rhythm of rectal
      motor complexes in fully ambulant subjects. Because a meal is a powerful and
      physiologic stimulus to elicit colonic pressure activity, we also studied the
      effect of a meal on these rectal motor complexes. METHODS: Prolonged ambulant
      anorectal pressure recordings were performed in 12 healthy volunteers
      (male:female ratio, 6:6; median age, 27 (range, 22-53) years). A total of 139
      rectal motor complexes were observed in >300 hours of recording. RESULTS: All
      subjects exhibited rectal motor complexes during the daytime, whereas in five
      subjects, no rectal motor complexes were observed during sleep. The number of
      rectal motor complexes was significantly lower during sleep (diurnal vs.
      nocturnal, 8 vs. 1 per subject, P < 0.0001). Furthermore, the duration and peak
      amplitude of these nocturnal rectal motor complexes were significantly reduced.
      On the ambulant recordings, the subjects marked a total of 20 meals. During the
      first 2 hours after these meals, rectal motor complexes were noted in 65 percent
      of the cases. The postprandial frequency of rectal motor complexes was
      significantly higher than the overall frequency (2/hour vs. 0.4/hour, P = 0.004).
      CONCLUSIONS: These findings suggest that sleep results in a reduction of rectal
      motor activity, whereas a meal provides a stimulus for increased rectal motor
      activity in fully ambulant subjects.

PMID- 11584211
TI  - Anatomic study of the lymph nodes of the mesorectum.
AB  - PURPOSE: Lymph node involvement is the most important prognostic factor when
      staging patients with colorectal cancer. The probability of detecting metastasis
      grows with the number of nodes examined. However, the number of nodes found in
      surgical specimens varies substantially. We have therefore determined the number
      and distribution of lymph nodes in the mesorectum by cadaveric dissection.
      METHODS: Twenty formalin-fixed cadaveric pelvises were dissected (13 males). The
      search for lymph nodes was performed in a systematic way, from the division of
      the superior rectal artery following the smallest visible branches to the level
      of the anorectal ring. RESULTS: A total of 168 lymph nodes were found in 20
      mesorectal blocks, with a mean (standard deviation) number per specimen of 8.4
      (4.45). Lymph node size ranged from 2 to 10 mm. Distribution of lymph nodes in
      mesorectum was as follows: 120 nodes (71.4 percent) were found around the
      branches of the superior rectal artery proximal to the peritoneal reflection, and
      48 nodes (28.6 percent) were found distal to the peritoneal reflection. Fourteen
      specimens (70 percent) had lymph nodes at the division of the superior rectal
      artery. CONCLUSIONS: The mean number of lymph nodes found in the mesorectum
      distal to the superior rectal artery division was 8.4. Most of these lymph nodes
      were proximal to the peritoneal reflection. The range found in the number of
      lymph nodes per case should be considered for use in the formulation of
      guidelines in anatomicopathologic studies of surgical specimens obtained after
      mesorectal excision.

PMID- 11584213
TI  - Rectal sensory perception in females with obstructed defecation.
AB  - PURPOSE: Parasympathetic afferent nerves are thought to mediate rectal filling
      sensations. The role of sympathetic afferent nerves in the mediation of these
      sensations is unclear. Sympathetic nerves have been reported to mediate
      nonspecific sensations in the pelvis or lower abdomen in patients with blocked
      parasympathetic afferent supply. It has been reported that the parasympathetic
      afferent nerves are stimulated by both slow ramp (cumulative) and fast phasic
      (intermittent) distention of the rectum, whereas the sympathetic afferent nerves
      are only stimulated by fast phasic distention. Therefore, it might be useful to
      use the two distention protocols to differentiate between a parasympathetic and
      sympathetic afferent deficit. METHODS: Sixty control subjects (9 males; median
      age, 48 (range, 20-70) years) and 100 female patients (median age, 50 (range, 18
      75) years) with obstructed defecation entered the study. Rectal sensory
      perception was assessed with an "infinitely" compliant polyethylene bag and a
      computer-controlled air-injection system. This bag was inserted into the rectum
      and inflated with air to selected pressure levels according to two different
      distention protocols (fast phasic and slow ramp). The distending pressures needed
      to evoke rectal filling sensations, first sensation of content in the rectum, and
      earliest urge to defecate were noted, as was the maximum tolerable volume.
      RESULTS: In all control subjects, rectal filling sensations could be evoked.
      Twenty-one patients (21 percent) experienced no sensation at all in the pressure
      range between 0 and 65 mmHg during either slow ramp or fast phasic distention.
      The pressure thresholds for first sensation, earliest urge to defecate, and
      maximum tolerable volume were significantly higher in patients with obstructed
      defecation (P < 0.001). In each subject, the pressure thresholds for first
      sensation, earliest urge to defecate, and maximum tolerable volume were always
      the same, regardless of the type of distention. CONCLUSION: Rectal sensory
      perception is blunted or absent in the majority of patients with obstructed
      defecation. The observation that this abnormality can be detected by both
      distention protocols suggests that the parasympathetic afferent nerves are
      deficient. Because none of the patients experienced a nonspecific sensation in
      the pelvis or lower abdomen during fast phasic distention, it might be suggested
      that the sympathetic afferents are also deficient. This finding implies that it
      is not worthwhile to use different distention protocols in patients with
      obstructed defecation.

PMID- 11584215
TI  - Local excision of rectal cancer: what is the evidence?
AB  - PURPOSE: Although local excision of rectal cancers is a less morbid alternative
      to radical resection, its role as a curative procedure is unclear. The role of
      adjuvant therapy after local excision is also controversial. This review aims to
      examine current evidence on local excision of rectal cancers and how it fits into
      the management algorithm for rectal cancer. METHODS: A literature review was
      undertaken through the MEDLINE database and by cross-referencing previous
      publications, thus identifying 41 studies on curative local excision of rectal
      cancer published in English. Details of preoperative staging, surgical
      procedures, adjuvant therapy, follow-up, and outcome measures, including
      complications, survival data, recurrences, and salvage were examined. RESULTS:
      Preoperative staging of rectal cancers is variable. Digital rectal examination
      and computerized tomography are used in most studies. Endorectal ultrasound is
      used in some patients in 9 of 41 studies. Local excision preserves anorectal
      function, and seems to have limited morbidity (0-22 percent). Local excision
      alone is associated with local recurrences in 9.7 (range, 0-24) percent of T1, 25
      (range, 0-67) percent of T2 and 38 (range, 0-100) percent of T3 cancers. The
      addition of adjuvant chemoradiotherapy after local excision yields local
      recurrence rates of 9.5 (range, 0-50) percent for T1, 13.6 (range, 0-24) percent
      for T2, and 13.8 (range, 0-50) percent for T3 cancers. Data on local excision
      after preoperative chemoradiotherapy for tumor down staging are limited. Factors
      other than T-stage that lead to higher local recurrence rates after local
      excision include poor histologic grade, the presence of lymphovascular invasion,
      and positive margins. Local recurrences after local excision can be surgically
      salvaged (84 of 114 patients in 15 studies), with a disease-free survival rates
      between 40 and 100 percent at a follow-up of 0.1 to 13.5 years. CONCLUSIONS:
      Local excision for rectal cancers is associated with a low morbidity and provides
      satisfactory local control and disease-free survival rates for T1 rectal cancers.
      There is, however, a need for a randomized, controlled trial for T2 cancers,
      comparing local excision with adjuvant chemoradiotherapy to radical resection.

PMID- 11584216
TI  - Nonsteroidal anti-inflammatory drug-induced strictures of the colon: report of a
      case and review of the literature.
AB  - The phenomenon of strictures of the colon induced by nonsteroidal anti
      inflammatory drugs is a newly recognized pathologic entity that has gained little
      exposure in the surgical literature to date. A further case is reported and the
      clinical features of this entity are discussed. Most patients present with
      symptoms suggestive of malignancy, namely anemia, obstructive symptoms, or weight
      loss. Pathologic changes are characterized by diaphragm-like strictures with
      submucosal fibrosis. Surgical resection to exclude malignancy and treat symptoms
      along with cessation of the nonsteroidal anti-inflammatory drug is the treatment
      of choice.

PMID- 11584217
TI  - Testicular metastasis from ileal carcinoid: report of a case.
AB  - PURPOSE: This report presents a patient with testicular metastasis from an ileal
      carcinoid. METHODS: This was a retrospective case review with literature review.
      RESULTS: The patient underwent right orchiectomy for a solid mass. Pathology
      revealed carcinoid tumor. Octreotide scan showed increased concentration in the
      right lower quadrant of the abdomen. Computerized tomography results were
      negative. Colonoscopy with biopsy revealed carcinoid of the terminal ileum. The
      patient underwent an elective resection of the terminal ileum and the right
      colon. Pathology revealed carcinoid tumor with vascular and lymphatic invasion
      present, and eight lymph nodes were positive. The patient had adjuvant treatment
      with octreotide. CONCLUSION: Carcinoid tumors have been reported to metastasize
      to numerous areas. This is the first report of testicular metastasis from ileal
      carcinoid. Primary carcinoids of the testicle have been reported also. The
      clinician should be aware of this rare metastatic event. When pathology reveals
      carcinoid of the testicle, metastatic disease should be excluded before the tumor
      is identified as primary.

PMID- 11584218
TI  - Primary osteosarcoma arising in the colon: report of a case.
AB  - A 53-year-old female presented with abdominal pain, and computed tomography scan
      revealed a small, calcified lesion in the wall of the transverse colon. The
      symptoms later disappeared spontaneously, and she remained in good health.
      However, four years later, she developed lancinating abdominal pain and was
      admitted to our hospital. A large tumor with calcification was found in the left
      upper abdominal cavity. Curative resection of the tumor was performed, and the
      histology was compatible with extraskeletal osteosarcoma. We speculated that the
      tumor originated from the colonic wall, because a small calcification was
      observed in the wall of the transverse colon four years before surgery. To the
      best of our knowledge, this is the first report of primary colonic osteosarcoma.

PMID- 11584220
TI  - New, simple, ultrasound-guided infiltration of the pudendal nerve: topographic
      basics.
AB  - PURPOSE: We report the topographic relationship of the pudendal nerve to the
      accompanying pudendal vessels and the ischial spine and provide the basics for an
      ultrasonographic depiction of these structures. METHODS: Twenty-nine female and
      29 male adult human cadavers were positioned prone to expose the deep gluteal
      region. In 58 left and 58 right pelves the course of the pudendal nerve and
      vessels at the ischial spine were evaluated and analyzed statistically (n = 116).
      RESULTS: Multitrunked pudendal nerves were found in 40.5 percent with a left-vs.
      right ratio of 1:1.5. The diameters of the single-trunked nerves ranged from 1.3
      to 6.8 (mean 3.6 +/- 1.1) mm. In 75.9 percent the pudendal nerve was found medial
      to the accompanying internal pudendal artery. The distance to the artery ranged
      from 17.2 mm medial to 8 mm lateral (mean, 3.4 mm medial +/- 4.1 mm). The
      distance to the tip of the ischial spine ranged from 13.4 mm medial to 7.4 mm
      lateral (mean, 2.1 mm medial +/- 3.7 mm). CONCLUSIONS: The knowledge of the close
      spatial relationship between the pudendal nerve and the internal pudendal artery
      is important for any infiltration technique and even surgical release. It demands
      real-time, visually controlled infiltration techniques, such as with ultrasound.

PMID- 11584219
TI  - Malacoplakia simulating organ invasion in a rectosigmoid adenocarcinoma: report
      of a case.
AB  - Malacoplakia is a histiocytic inflammatory response that may be associated with
      colorectal tumors. We report the case of a 65-year-old male taking steroids for a
      severe pulmonary disease. He presented with a rectosigmoid tumor that seemed to
      infiltrate the urinary bladder and the sacrum on the preoperative CT scan and
      echography and at laparotomy. A low anterior resection en bloc with a partial
      cystectomy was performed. The pathologic analysis showed a pT3pN0 adenocarcinoma
      with an extensive malacoplakia infiltrating the bladder and the pericolic and
      perirectal tissues. This case report emphasizes the overstaging that malacoplakia
      may induce and underlines a situation the surgeon may possibly confront. Our
      observation confirms the association of malacoplakia, colorectal carcinoma, and
      steroid treatment.

PMID- 11584221
TI  - New, simple, ultrasound-guided infiltration of the pudendal nerve:
      ultrasonographic technique.
AB  - PURPOSE: Anesthetic infiltration of the pudendal nerve at the ischial spine can
      relieve perineal pain in cases of compression or distention. The aim of our study
      was to look for a real-time, visually controlled infiltration technique using
      ultrasound. METHODS: Fifty-three volunteers were examined in a prone position
      using a 3.5-MHz curved-array probe in color-coded Doppler mode. The deep gluteal
      region was scanned in two perpendicular planes, longitudinal and transverse to
      the internal pudendal artery. RESULTS: On the transverse planes the ischial
      spine, the sacrospinous ligament, and the internal pudendal artery were depicted
      in all but two cases. In 47.2 percent of the cases one trunk of the pudendal
      nerve was detected directly. Nerves consisting of more than one trunk were not
      found. The thickness of the nerve ranged between 3.5 and 7 mm. CONCLUSIONS: In
      almost one-half of the cases a direct ultrasound-guided infiltration of the
      pudendal nerve is possible. In the remaining cases the nerve can be detected and
      blocked indirectly, using the ischial spine or the internal pudendal artery as a
      landmark.

PMID- 11584222
TI  - Technique for ileoanal anastomosis.

PMID- 11584223
TI  - Temporal behavior of intraarticular gadolinium.
AB  - PURPOSE: As imaging delays during MR arthrography can result in suboptimal
      studies and potential pitfalls in diagnosis, we sought to evaluate the temporal
      behavior of intraarticular Gd-DTPA. METHOD: We prospectively studied four
      shoulders, four knees, and four hips. Two of each group received either an
      intraarticular injection of 3 mmol/L Gd-DTPA and iodinated contrast medium or 2
      mmol/L Gd-DTPA and 0.9% saline. We measured contrast-to-noise ratio (CNR) and
      joint distention on serial T1-weighted sequences. Retrospectively, we measured
      CNR and imaging delays in 31 MR arthrography patients (20 shoulders, 7 knees, and
      4 hips). RESULTS: In the shoulder, maximal CNR and joint distention occurred at
      15 min. CNR decreased 53% by 1 h. In the knee, maximal distention occurred at 1
      h, whereas CNR peaked at 2.75 h and then declined 20 and 86% by 3.5 and 6.25 h,
      respectively. In the hip, peak CNR and distention occurred at 0.5 h. CNR declined
      53% by 2 h. Both contrast mixtures yielded similar results. CONCLUSION: MR
      arthrography may tolerate imaging delays of 1 h for the shoulder, 2 h for the
      hip, and 3.5 h for the knee.

PMID- 11584224
TI  - Partial interosseous ligament tears of the wrist: difficulty in utilizing either
      primary or secondary MRI signs.
AB  - PURPOSE: Prior reports on scapholunate ligament (SLL) and lunotriquetral ligament
      (LTL) tears have evaluated complete tears. As these complete tears have markedly
      different biomechanical manifestations and surgical considerations than do
      partial tears, we evaluated the accuracy of MR and the usefulness of secondary MR
      signs to diagnose partial interosseous ligament tears. METHOD: Fifty wrists in 50
      patients underwent arthroscopy following 1.5 T MR. Images were evaluated by two
      independent blinded observers for normal or partially torn SLL and LTL and for
      three secondary signs potentially seen as mechanical sequelae of tears: osseous
      offset, arc disruption, or focal osteoarthritis. RESULTS: Arthroscopically, there
      were 16 SLL and 14 LTL partial tears. Accuracy of primary MR signs of partial
      tears was lower than that described in the literature for complete tears
      [sensitivity/specificity (kappa) = 0.56/0.56 (0.12)-SLL, 0.31/0.76 (0.13)-LTL].
      Secondary signs showed low sensitivity but high specificity, particularly for LTL
      tears: arc disruption [0.17/0.83 (0.43)-SLL, 0.0/1.00 (1.0)- LTL], focal
      osteoarthritis [0.32/0.78 (0.18)-SLL, 0.11/0.91 (0.12)-LTL], and focal osseous
      offset [0.39/0.75 (0.10)-SLL, 0.26/0.93 (0.39)-LTL]. Additionally, there was poor
      interobserver consistency for both primary and secondary signs. CONCLUSION: The
      sensitivity of morphologic evaluation for diagnosing partial intercarpal ligament
      tears, particularly those of the LTL, is limited. Secondary signs increase
      specificity but have low sensitivity, and with the exception of arc disruption,
      all signs had poor interobserver agreement.

PMID- 11584225
TI  - Injuries to the distal gastrocnemius muscle: MR findings.
AB  - PURPOSE: The purpose of this work was to demonstrate the MR findings of injuries
      to the distal gastrocnemius muscle. METHOD: Twenty patients with clinically
      confirmed injuries to the distal gastrocnemius muscle underwent MRI. The injuries
      were evaluated with regard to abnormal morphology or signal abnormality, site,
      and degree of tearing. RESULTS: Twenty-three injuries to the distal gastrocnemius
      occurred in 20 patients, with involvement of the myotendinous junction in 22 of
      23 (96%) injuries. An interstitial tear of the proximal Achilles tendon was
      present in one instance. Myotendinous strains were the most common injuries
      (10/23; 43%); partial tears (7/23; 30%) and complete tears (5/23; 22%) of the
      myotendinous junction or proximal Achilles tendon were less frequent. When an
      injury to the gastrocnemius myotendinous junction was present, involvement of the
      medial head (19/22; 86%) was more frequent than involvement of the lateral head
      (3/22; 14%). CONCLUSION: MRI allows accurate imaging of distal gastrocnemius
      muscle injuries. When occurring, distal gastrocnemius muscle injuries most
      frequently involve the myotendinous junction of the medial gastrocnemius head and
      occasionally the lateral gastrocnemius head or the proximal Achilles tendon.

PMID- 11584226
TI  - MR assessment of meniscal movement during knee flexion: correlation with the
      severity of cartilage abnormality in the femorotibial joint.
AB  - PURPOSE: The purpose of this study was to assess the degree of meniscal movement
      during knee flexion on MR images and to correlate it with the severity of
      cartilage damage in the femorotibial joint. METHOD: Sagittal MR images were
      obtained at extension and 45 degrees of flexion in 35 knees. A shortening ratio
      in the distance between the anterior and posterior horns at 0-45 degrees of knee
      flexion was calculated in each meniscus and was correlated with the degree of
      cartilage abnormality in the femorotibial joint. RESULTS: The shortening ratio of
      the meniscus was reduced in knees with cartilage abnormality in the femorotibial
      joint. The shortening ratio of the medial meniscus was inversely correlated with
      the degree of cartilage abnormality in the medial femoral condyle and with that
      in the medial tibial plateau. CONCLUSION: Restricted shortening ratio of the
      meniscus may be related to cartilage damage in the femorotibial joint.

PMID- 11584227
TI  - Dixon quantitative chemical shift MRI for bone marrow evaluation in the lumbar
      spine: a reproducibility study in healthy volunteers.
AB  - PURPOSE: The purpose of this work was to explore the reproducibility of fat
      fraction measurements using Dixon quantitative chemical shift imaging (QCSI) in
      the lumbar spine (L3, L4, and L5) of healthy volunteers. METHOD: Sixteen healthy
      volunteers were examined at 1.5 T two times to obtain a repeated measurement in
      the same slice and a third time in three parallel slices. Single slice, two point
      Dixon SE (TR/TE 2,500/22.3) sequences were used, from which fat-fraction images
      were calculated. The fat-fraction results are presented as averages over regions
      of interest, which were derived from the contours of the vertebrae.
      Reproducibility measures related to repeated measurements on different days,
      slice position, and contour drawing were calculated. RESULTS: The mean fat
      fraction was 0.37 (SD 0.08). The SD due to repeated measurement was small (sigmaR
      = 0.013-0.032), almost all of which can be explained by slice-(re)-positioning
      errors. CONCLUSION: When used to evaluate the same person longitudinally in time,
      Dixon QCSI fat-fraction measurement has an excellent reproducibility. It is a
      powerful noninvasive tool in the evaluation of bone marrow composition.

PMID- 11584228
TI  - Differentiation of calcification from chronic hemorrhage with corrected gradient
      echo phase imaging.
AB  - PURPOSE: The purpose of the current study was to prospectively evaluate the role
      of corrected gradient echo phase imaging in differentiation of calcified
      granuloma from chronic hemorrhage. METHOD: Eighty-five patients with
      single/multiple calcifications and hemorrhages irrespective of their location
      were studied with corrected gradient echo phase imaging. In all the cases, CT was
      used as the gold standard for the presence/absence of calcification. RESULTS: All
      calcified lesions showed positive phase, whereas chronic hemorrhages showed
      negative phase in all cases. Five calcified lesions showed no phase shift at TE
      =15 ms and positive shift at TE = 35 ms. Heterogeneous phase shift was observed
      in three calcified lesions at TE = 35 ms; all three lesions showed positive phase
      shift at TE = 15 ms. There was no site-specific problem in differentiation of
      calcification from chronic hemorrhage including in the basal ganglia. CONCLUSION:
      We conclude that calcified granuloma can be easily differentiated from chronic
      hemorrhage with corrected gradient echo phase imaging, which may obviate the need
      for CT for its confirmation.

PMID- 11584229
TI  - Short-echo time proton MR spectroscopy in the presence of gadolinium.
AB  - PURPOSE: The purpose of this work was to quantify the impact of contrast agents
      on short-TE single-voxel 1H MR spectroscopy (MRS) diagnosis of recurrent brain
      tumors. METHOD: Short-TE 1H MRS was performed in 49 patients with biopsy-proven
      brain tumors and 14 control subjects. Eight patients (nine paired exams) were
      examined before and after administration of Gd-DTPA (interval approximately 5-7
      min). RESULTS: Tumor spectra showed increased choline/creatine ratio (Cho/Cr; p <
      0.009) and Cho concentrations (p < 0.02). Receiver operator characteristic for
      Cho/Cr = 0.93 differentiated 100% of tumors from control in the absence or
      presence of contrast agent. Repeated 1H MRS varied <3%. Cho T2 was significantly
      longer than Cr T2 (p < 0.02). CONCLUSION: Proton MRS with TE of 30 ms may safely
      be used in combined contrast-enhanced MRI/MRS protocols. Further study is
      required with long-TE MRS because of the prolonged T2 of Cho.

PMID- 11584230
TI  - Serial proton magnetic resonance spectroscopy in lesions of Balo concentric
      sclerosis.
AB  - OBJECTIVE: Balo concentric sclerosis is a rare demyelinating disorder. Serial
      proton magnetic resonance spectroscopic (1H-MRS) studies were carried out to
      better understand the biochemical changes within concentric lesions. MATERIALS
      AND METHODS: Five concentric lesions in four patients with Balo concentric
      sclerosis were chosen as the objects of serial observation. They included two
      early acute lesions (showing as concentric ring enhancement on magnetic resonance
      imaging (MRI) after gadolinium administration), two late acute lesions (showing
      as marginal enhancement on MRI), and one early subacute lesion (showing as
      edematous concentric lesions without enhancement on MRI). The duration of follow
      up ranged from 2-23 months (mean 10 months). A total of 20 1H-MRS studies were
      performed. On each 1H-MRS study, short-echo (30 ms) and long-echo (136 ms)
      spectra were obtained. The peaks of N-acetyl-asparate (NAA), choline-containing
      compounds (Cho), creatine and phosphocreatine (Cr), lactate, and mobile lipid
      were observed and compared. RESULTS: Generally, a decrease of NAA/Cr ratio and an
      increase of Cho/Cr ratio were seen on all the spectra. Observing longitudinally,
      a trend of decreasing NAA/Cr ratio first and then partially recovering later was
      noted. The lowest level of NAA/Cr ratio was noted at the late acute stage or
      early subacute stage. The Cho/Cr ratio and amplitude of the lactate peak showed a
      similar trend as that of NAA/Cr, but in an opposite direction. It was rising
      first and descending later. The highest levels of Cho/Cr ratio and lactate peak
      were also observed at the late acute or early subacute stage. In addition,
      lactate peaks could be detected as long as 7 months after onset of symptoms.
      Lipid metabolite (two broad peaks at 0.9-1.5 ppm) was seen at the initial study
      of each group, but fluctuated in size on follow-up. CONCLUSION: The
      characteristic biochemical changes of concentric sclerosis were a decreased
      NAA/Cr ratio, an increased Cho/Cr ratio, two broad peaks at 0.9-1.5 ppm, lactate
      production, and a reversible NAA/Cr ratio on follow-up. The serial 1H-MRS studies
      revealed a strong biochemical association between NAA, Cho, and lactate, which
      may be caused by the same pathogenetic process of demyelination and inflammatory
      cellular infiltration. The specificity of the serial changes may provide
      information about the stage of the concentric lesion and perhaps aid in
      monitoring progression of concentric lesions and evaluating therapy.

PMID- 11584231
TI  - Congenital malformations of the inner ear and the vestibulocochlear nerve in
      children with sensorineural hearing loss: evaluation with CT and MRI.
AB  - PURPOSE: The purpose of this work was to study the diagnostic value of CT and MRI
      in children with sensorineural hearing loss and to analyze anatomic abnormalities
      of the inner ear and the vestibulocochlear nerve in this patient group. METHOD:
      We evaluated 42 inner ears in 21 children with congenital deafness who had
      congenital inner ear malformations and who were candidates for cochlear implants.
      All patients were studied with high resolution MR and helical CT examinations.
      The MR study included a T2-weighted 3D fast SE sequence. We describe and tabulate
      the anatomic abnormalities. Special attention was given to abnormalities of the
      vestibulocochlear nerve. The field of view in the plane according to the length
      axis of the internal auditory canal (IAC) was 4 cm. Additional continuous
      parasagittal reformations perpendicular to the length axis of the IAC were
      studied with a field of view of 3 cm. RESULTS: CT and MRI allowed accurate
      identification of malformations of the inner ear in children with congenital
      deafness. We identified 99 malformations, with a majority of patients
      demonstrating multiple abnormalities. Common imaging findings were Mondini
      abnormality and Mondini variants (12/42) and fusion of the lateral or superior
      semicircular canal with the vestibule (12/42). MRI demonstrated in 9 of 21
      patients a rudimentary or absent vestibulocochlear nerve in the auditory canal.
      CONCLUSION: CT and MRI are important modalities to analyze the inner ear in
      children who are candidates for cochlear implants. MRI with an extremely small
      field of view should be used to study possible abnormalities of the
      vestibulocochlear nerves. This may alter clinical care and allow cochlear implant
      placement in patients whose electrodiagnostic studies suggest that the implant
      should not be performed. The detailed analysis of abnormalities of the inner ear
      might establish prognostic factors.

PMID- 11584232
TI  - Role of enhanced MRI in the follow-up of patients with medically refractory
      trigeminal neuralgia undergoing stereotactic radiosurgery using the gamma knife:
      initial experience.
AB  - PURPOSE: The purpose of this work was to evaluate the early posttreatment MR
      findings, and their clinical utility, in patients with trigeminal neuralgia
      undergoing stereotactic radiosurgery using the gamma knife. METHOD: Twenty-six
      patients with medically refractory trigeminal neuralgia underwent stereotactic
      radiosurgery. A single dose of 70-90 Gy was administered to the proximal root
      entry zone (n = 21) or the retrogasserian portion (n = 5) of the trigeminal
      nerve. Posttreatment enhanced MRI and clinical assessment were performed at 3-6
      months. RESULTS: Five patients did not have radiologic follow-up. There were no
      changes identified in the treated trigeminal nerve or adjacent brainstem in 19 of
      21 patients. Two patients with multiple sclerosis developed abnormal signal and
      enhancement in the brainstem and/or trigeminal nerve; neither had clinical
      complications. Onset of therapeutic effect ranged from 3 weeks to 3 months; 19
      patients had a beneficial response. CONCLUSION: Results of enhanced MRI 3-6
      months after stereotactic radiosurgical treatment of trigeminal neuralgia do not
      correlate with the clinical response. Because beneficial clinical responses or
      treatment failures are apparent by 3 months, routine posttreatment MRI in these
      patients is not warranted.

PMID- 11584233
TI  - Acute neck infections: prospective comparison between CT and MRI in 47 patients.
AB  - PURPOSE: The purpose of this work was to assess the advantages and disadvantages
      of MRI versus CT in the initial evaluation of acute infections involving the
      neck. METHOD: We prospectively evaluated 47 patients with neck infections. All
      patients underwent CT and MRI with contrast of the area of interest using similar
      slice thickness. Final diagnosis was achieved by percutaneous aspiration,
      surgical exploration and drainage, or follow-up after successful antibiotic
      therapy in all patients. Two radiologists reviewed all imaging studies with
      special attention to lesion conspicuity, location, extension, bone involvement,
      source of infection (odontogenic versus nonodontogenic), and presence of gas
      and/or calcium in the lesions. A 3 point scale was used to grade these
      parameters, and statistical comparison was done using paired t test. RESULTS: As
      used in our population, MRI was superior to CT in regard to lesion conspicuity,
      number of anatomic spaces involved, extension, and source. Additionally, although
      not statistically significantly, MRI detected a greater number of abscess
      collections. CT was superior to MRI in the detection of intralesional gas and
      calcium and showed fewer motion artifacts. These advantages of CT were, however,
      not significantly better than those of MRI. CONCLUSION: As used in our study, MRI
      was considered superior to CT in the initial evaluation of neck infections. Our
      findings suggest that MRI may be used as the first and perhaps the only modality
      to initially evaluate patients with neck infections when clinically feasible.

PMID- 11584234
TI  - Prognostic value of intraventricular blood in perimesencephalic nonaneurysmal
      subarachnoid hemorrhage.
AB  - INTRODUCTION: Perimesencephalic nonaneurysmal subarachnoid hemorrhage (PNSH) is a
      distinct type of subarachnoid hemorrhage with a characteristic bleeding pattern,
      and an excellent clinical outcome. However, the clinical course of patients
      presenting with a perimesencephalic nonaneurysmal bleeding pattern and
      intraventricular blood has not yet been investigated. MATERIALS AND METHODS: In
      this retrospective study we describe the cisternal blood distribution and the
      clinical course of 34 PNSH patients with (10 patients) and without (24 patients)
      intraventricular blood. RESULTS/DISCUSSION: Patients without intraventricular
      blood were in good clinical condition on admission; the in-hospital course was
      uneventful except for acute hydrocephalus, which was detected in two cases and
      improved spontaneously in both patients. All patients resumed their previous
      lifestyles. In contrast, two patients with PNSH and intraventricular blood were
      drowsy and had focal neurologic deficits on admission. Four patients developed an
      acute hydrocephalus, and two of these patients needed ventricular shunting. There
      was evidence for delayed cerebral ischemia in one of these patients. Outcome was
      excellent in eight cases, and one patient was moderately and one patient was
      severely disabled at dismissal from the hospital. Rebleeding did not occur in all
      patients, and repeated four-vessel angiography did not reveal the source of
      bleeding in any of our patients. CONCLUSION: Our data indicate that the presence
      of intraventricular blood may be a good indicator for the development of acute
      hydrocephalus in PNSH. Moreover, our results suggest that PNSH patients with
      ventricular blood may have a higher complication rate and a poorer outcome
      compared with PNSH patients without intraventricular blood.

PMID- 11584235
TI  - Performance evaluation of an automated system for registration and postprocessing
      of CT scans.
AB  - A prototype system optimized for automatic registration of CT scans and
      applications such as subtraction enhancement and CT angiography was evaluated. Co
      registration was performed on 50 studies of various types, including CT
      angiograms. Mean registration speed was 109 s; accuracy was 2.0 mm. Examples of
      subtraction enhancement and automatic extraction of the vascular tree are
      provided. Unattended registration was demonstrated in routine application.
      Subtraction-enhanced images and extraction of the vascular tree may be useful in
      clinical practice.

PMID- 11584236
TI  - Thin-section CT features of intrapulmonary lymph nodes.
AB  - PURPOSE: The objective of this study was to evaluate CT findings of
      pathologically proven intrapulmonary lymph nodes (IPLNs) and discuss the utility
      of thin-section CT and contrast-enhanced CT. METHOD: CT findings of 18 nodules in
      14 patients with pathologically proven IPLNs were reviewed. CT scanning of the
      whole lung was performed contiguously with slice thickness of 10 mm. In addition,
      a helical scan with slice thickness of 2 mm was performed in nine patients,
      focusing on the nodule. Contrast-enhanced helical CT was performed in four
      patients, and the utility of thin section CT and contrast-enhanced CT was
      investigated. RESULTS: One patient had three nodules, 2 patients had two nodules,
      and the remaining 11 patients had a solitary nodule. All nodules were located
      below the level of the carina and within 15 mm of the pleura. In one case,
      conventional CT revealed the nodule 20 mm away from the pleura; however, the
      nodule attached to the major fissure was clearly revealed on thin-section CT. The
      size of the nodules was < or =15 mm, and the shape was round (n = 8), oval (n =
      9), or lobulated (n = 1) with sharp border. One nodule demonstrated a spiculated
      border due to a surrounding pulmonary fibrosis on conventional CT; however, thin
      section CT showed precisely a sharp border. The lobulated shape of one case
      histopathologically reflected a hilus of lymph node. On contrast-enhanced helical
      CT, all four nodules were enhanced and the degree enhancement was 36-85 HU
      (median 66.6 HU). CONCLUSION: In current times, IPLNs are not uncommon lesions.
      We should consider IPLN in the differential diagnosis of solitary or multiple
      pulmonary nodules in the peripheral field and below the level of the carina. Thin
      section CT showed precisely the border or relation between IPLNs and the
      surrounding structure. It was difficult to distinguish between IPLNs and
      malignant nodules from the degree of enhancement on contrast-enhanced CT. On thin
      section and contrast-enhanced CT, the findings of IPLNs are not necessarily
      specific. Therefore, strict observation on CT is necessary; in certain cases that
      are increasing in size, video-assisted thoracic surgery should be considered
      because of their location.

PMID- 11584237
TI  - Interstitial pneumonia in progressive systemic sclerosis: serial high-resolution
      CT findings with functional correlation.
AB  - PURPOSE: The aim of our study was to assess the serial high-resolution CT
      findings and their correlation with the results of pulmonary function tests in
      patients with progressive systemic sclerosis (PSS) and interstitial pneumonia.
      METHOD: The study included 40 patients with symptoms or signs of PSS and
      interstitial pneumonia, who underwent serial high-resolution CT scans (mean
      follow-up period 39 months). Seventeen patients simultaneously had serial
      pulmonary function tests (mean follow-up period 40 months). On high-resolution
      CT, the pattern and extent of parenchymal abnormalities were retrospectively
      analyzed. Serial changes on high-resolution CT were correlated with the changes
      of pulmonary function tests. RESULTS: On initial CT, areas of ground-glass
      opacity (mean +/- SD extent 17.7 +/- 12.3% in all patients), irregular linear
      opacity (4.4 +/- 4.4% in 36 patients), small nodules (3.9 +/- 12.5% in 28),
      consolidation (1.9 +/- 4.2% in 13), and honeycombing (1.9 +/- 3.8% in 12) were
      seen. The total disease extent (p = 0.042) and extents of ground-glass opacity
      (18.9 +/- 15.5%; p = 0.04) and honeycombing (5.0 +/- 7.2%; p = 0.002) increased
      significantly on follow-up CT. Both forced vital capacity (from 2.4 +/- 0.4 to
      2.0 +/- 0.4 L; p = 0.002) and forced expiratory volume in 1 s (from 2.0 +/- 0.4
      to 1.6 +/- 0.3 L; p = 0.013) decreased significantly on follow-up examination.
      The increase in the extent of honeycombing on CT correlated significantly with
      the decrease in diffusing capacity for carbon monoxide (r = -0.411, p = 0.049).
      CONCLUSION: In patients with PSS and interstitial pneumonia, the overall extent
      of disease and extents of honeycombing and ground-glass opacity increase
      significantly on follow-up CT. Increase of honeycombing correlates well with
      decrease of diffusing capacity for carbon monoxide.

PMID- 11584238
TI  - Anomalous systemic arterial supply to normal basal segments of left lower lobe:
      characteristic imaging findings.
AB  - PURPOSE: The purpose of this study was to describe the characteristic findings in
      each imaging modality of anomalous systemic arterial supply to normal basal
      segments of the left lower lobe of the lung. METHOD: Five patients with anomalous
      systemic arterial supply to normal basal segments of the left lower lobe were
      retrospectively reviewed. Chest radiography, contrast-enhanced CT scan,
      angiography, and other imaging modalities were analyzed. RESULTS: The imaging
      findings of this anomaly were characterized by three issues as follows: an
      anomalous systemic artery arising from the thoracic aorta, absence of pulmonary
      arterial supply, and normal bronchial system as well as normal pulmonary
      parenchyma in the affected segments. The anomalous systemic artery was
      demonstrated on chest radiography, contrast-enhanced CT scan, MRI, and thoracic
      aortography. Absence of pulmonary arterial supply was revealed by pulmonary
      angiography, radiolabeled perfusion scan, and CT scan. Normal bronchial system
      was confirmed by radiolabeled ventilation scan, bronchography, and CT scan.
      CONCLUSION: CT is useful in making the correct diagnosis of this anomaly because
      it is the only diagnostic method that can demonstrate the anomalous systemic
      artery, absence of pulmonary arterial supply, and normal bronchial system in the
      affected segments.

PMID- 11584239
TI  - Splenic imaging with ultrasmall superparamagnetic iron oxide ferumoxtran-10 (AMI
      7227): preliminary observations.
AB  - PURPOSE: Ferumoxtran-10 (ultrasmall superparamagnetic iron oxide; Combidex, AMI
      7227) is a long-circulating MR contrast agent with reticuloendothelial uptake
      known to enhance tissue T1 and T2 relaxation rates. The purpose of this study was
      to assess the effect of ferumoxtran-10-enhanced MRI in evaluating focal splenic
      lesions. METHOD: Eighteen patients underwent MR evaluation of the spleen. Two of
      these patients with exophytic normal splenic tissue (splenules) and 13 of these
      patients with 24 focal splenic lesions (7 cysts, 2 hemangiomas, 7 metastases, 1
      infarct, 7 lymphoma) were assessed by T1-weighted gradient echo and T2-weighted
      fast SE MRI following intravenous administration of ferumoxtran-10 (1.1 mg of
      Fe/kg). Qualitative analysis involving improved lesion detection and/or
      characterization, additional information from postcontrast images affecting
      staging, and patient management was performed. Quantitative measurements of
      lesion-to-spleen contrast-to-noise ratio were also performed. RESULTS: Additional
      information was provided by ferumoxtran-10-enhanced images in 15 of 18 patients.
      In 8 of 15 (53%) patients, improved lesion detection (i.e., number of lesions)
      was obtained on contrast-enhanced images. Improved lesion visualization (i.e.,
      conspicuity) was noted in 11 of 15 (73%) of patients. In 10 of 15 (67%) patients,
      postcontrast imaging provided additional information leading to lesion
      characterization. Staging of disease and patient management were affected in 5 of
      15 (33%) and 6 of 15 (40%) patients, respectively. CONCLUSION: Ferumoxtran-10 is
      a promising contrast agent for the evaluation of focal splenic lesions.

PMID- 11584241
TI  - Correlations between colonic wall thickening in patients with virally induced
      cirrhosis on CT and clinical status.
AB  - PURPOSE: The purpose of this work was to determine the frequency and CT imaging
      spectrum of colonic wall thickening and correlate these with the clinical
      severity of virally induced cirrhosis. METHOD: Fifty-nine patients were
      identified with virally induced cirrhosis and no other causes of colonic wall
      thickening. The abdominal CT scans of these patients were retrospectively
      reviewed by two radiologists to determine the presence of colonic wall thickening
      from the ascending colon to the descending colon, to assess the segmental
      distribution, and to correlate these findings with the clinical status assessed
      by Child-Pugh classification, presence of ascites, splenic volume index, varices
      score, and serum albumin levels. RESULTS: Colonic wall thickening was identified
      in 18 (31%) patients. The frequency of the affected distribution of colonic wall
      thickening was as follows: ascending colon in 17 (29%) patients, transverse colon
      in 11 (19%) patients, and descending colon in 7 patients (12%). The ascending
      colon was the most common site of colonic wall thickening (p < 0.001). Ten (17%)
      patients had multisegmental distributions. Colonic wall thickening had a
      statistically significant association with Child-Pugh grades A, B, and C (p <
      0.0001), presence of ascites (p < 0.0004), splenic volume index (p = 0.0026),
      varices score (p < 0.0001), and serum albumin levels (p = 0.0364). The segmental
      distribution of wall thickening significantly correlated with Child-Pugh grades
      A, B, and C (p = 0.0005), presence of ascites (p < 0.001), varices score (p <
      0.0001), serum albumin levels (p < 0.0001), and splenic volume index (p =
      0.0135). CONCLUSION: Colonic wall thickening occurs commonly in patients with
      virally induced cirrhosis. The presence and number of colonic wall thickening
      were correlated with the grading of the severity of cirrhosis.

PMID- 11584240
TI  - Detection of hepatocellular carcinoma: combined T2-weighted and dynamic
      gadolinium-enhanced MRI versus combined CT during arterial portography and CT
      hepatic arteriography.
AB  - PURPOSE: The purpose of this study was to compare the preoperative detectability
      of hepatocellular carcinomas (HCCs) using combined T2-weighted and dynamic
      gadolinium-enhanced MRI and combined CT during arterial portography (CTAP) and CT
      hepatic arteriography (CTHA). METHOD: Thirty-three patients with 43 HCCs
      underwent T2-weighted and dynamic gadolinium-enhanced MRI and combined CTAP and
      CTHA. The diagnosis was established by pathologic examination following surgical
      resection in 26 patients and by biopsy in 7 patients. The MR protocol included
      fast SE with two TEs (including T2-weighted imaging) and precontrast and
      gadolinium-enhanced T1-weighted fast multiplanar spoiled gradient-recalled echo
      images with dynamic study. The MR images of all sequences and the paired CTAP and
      CTHA images were independently reviewed by three radiologists. Image review was
      conducted on a segment-by-segment basis. Diagnostic accuracy was evaluated with
      receiver operating characteristic analysis. RESULTS: The accuracies (Az values)
      of MRI of all sequences and combined CTAP and CTHA for all observers were 0.960
      and 0.959, respectively. The mean sensitivities of MRI and CT were 90 and 94%,
      respectively. The differences were not statistically significant. The mean
      specificity of MRI (99%) was significantly higher than that of combined CTAP and
      CTHA (92%). CONCLUSION: Combined T2-weighted and dynamic gadolinium-enhanced MRI
      is as accurate as combined CTAP and CTHA for preoperative detection of HCCs.

PMID- 11584242
TI  - Spiral CT findings in active and remission phases in patients with Crohn disease.
AB  - PURPOSE: The purpose of this study was to evaluate the radiologic findings in
      helical CT (HCT) that can be useful to differentiate patients with active Crohn
      disease (CD) from those in the remission phase. METHOD: Fifty patients diagnosed
      with cases of CD were classified into active or remission phases (n = 37 and n =
      13, respectively) according to clinical criteria and laboratory data. All of them
      underwent an abdominal HCT exploration. The following radiologic findings were
      evaluated: thickness, density and enhancement of the bowel wall, presence of
      "target" or "double halo," mesenteric involvement, and possible complications.
      RESULTS: All patients in the active phase had pathologic findings on HCT. The
      wall thickness was 8.5 (SD 3.2) and 6.5 mm (SD 4 mm) in active and remission
      phases, respectively (p = 0.06). Target was present in seven patients (19%) with
      active disease and in five patients (38.5%) in the remission phase (p = 0.15).
      Density of the wall in the active phase was 95 HU and in the remission phase 65
      HU (p < 0.002). Mesentery was involved in 89.2% of patients in the active phase
      and 38% of patients in the remission phase (p < 0.001). The complications
      observed in patients with active-phase disease were abscesses in nine (24%),
      phlegmons in two, fistulas in three, intestinal obstruction in two, and
      pancreatitis in one. CONCLUSION: A normal HCT rules out that a patient with CD is
      in the active phase of disease. The presence of significant bowel wall
      enhancement and mesentery involvement assists in the differentiation of patients
      in the active phase from those in remission. HCT is also effective to assess the
      presence of complications, which are indicative of the active phase.

PMID- 11584243
TI  - CT demonstration of dilated gonadal vein as a portosystemic shunt of mesenteric
      varices.
AB  - PURPOSE: The purpose of this work was to assess CT demonstration of the enlarged
      gonadal vein as a portosystemic shunt of mesenteric varices. METHOD: The clinical
      records and CT images of eight patients with angiographically confirmed
      mesenteric varices were studied retrospectively. We measured the size of the
      right gonadal vein of these eight patients and also measured the size of the
      right gonadal vein in 60 patients without mesenteric varices. RESULTS: In all
      eight patients, CT demonstrated that the mesenteric varices drained into the
      inferior vena cava through the dilated right gonadal vein (diameter 6-10 mm) in
      all and that the left gonadal vein was not dilated (diameter 2-3 mm). In 60
      patients without mesenteric varices, the diameter of the right gonadal vein was 1
      5 mm. CONCLUSION: CT demonstrates the dilated gonadal vein as a portosystemic
      shunt of the mesenteric varices. Awareness of a dilated gonadal vein in patients
      with portal hypertension may be helpful to consider the possibility of mesenteric
      varices.

PMID- 11584244
TI  - Celiomesenteric anomaly demonstration by multidetector CT and volume rendering.
AB  - Preoperative knowledge of vascular anomalies is critical to planning a surgical
      approach. We present a case of celiomesenteric anomaly. Multidetector CT and
      volume rendering give high quality angiograms and a multitude of perspectives
      that facilitate depiction and understanding of such anomalies.

PMID- 11584245
TI  - Regional spatial normalization: toward an optimal target.
AB  - PURPOSE: The purpose of this work was to develop methods for defining,
      constructing, and evaluating a "minimal deformation target" (MDT) brain for
      multisubject studies based on analysis of the entire group. The goal is to
      provide a procedure that will create a standard, reproducible target brain image
      based on common features of a group of three-dimensional MR brain images. METHOD:
      The average deformation and dispersion distance, derived from discrete three
      dimensional deformation fields (DFs), are used to identify the best individual
      target (BIT) brain. This brain is assumed to be the one with the minimal
      deformation bias within a group of MR brain images. The BIT brain is determined
      as the one with the minimal target quality score, our cost function based on the
      deformation displacement and dispersion distance. The BIT brain is then
      transformed to the MDT brain using an average DF to create an optimized target
      brain. This analysis requires the calculation of a large number of DFs. To
      overcome this limitation, we developed an analysis method (the fast method) that
      reduces the task from order N2 complexity to one of order N, a tremendous
      advantage for large-N studies. RESULTS: Multiscale correlation analysis in a
      group of 20 subjects demonstrated the superiority of warping using the MDT target
      brain, made from the BIT brain, over several individual and MDT-transformed
      target brains also from the group. CONCLUSION: Analysis of three-dimensional DF
      provides a means to quickly create a reproducible MDT target brain for any set of
      subjects. Warping to the MDT target was shown by an independent multiscale
      correlation method to produce superior results.

PMID- 11584246
TI  - Improving image contrast using principal component analysis for subsequent image
      segmentation.
AB  - This article presents a technique for improving MR image contrast by linearly
      combining multiple MR images with different tissue contrast. The weighting
      coefficients of the linear combination are derived using principal component
      analysis. The contrast-enhanced composite image is segmented subsequently using
      gray level-based 1D segmentation methods. The technique reduces a multispectral
      image set to composite eigenimages and allows application of appropriate 1D
      segmentation methods that do not have equivalent counterparts in multispectral
      methods.

PMID- 11584247
TI  - Sectional neuroanatomy of the lower limb II: leg and foot.
AB  - The authors have produced a pair of articles that can be used to rapidly identify
      back, hip, and lower limb muscles and their innervation(s). This article presents
      the motor and sensory innervation of the lower limb by color-coding structures to
      match their peripheral nerves. It provides a companion summary table that allows
      prediction of unique patterns of denervation from 12 lesions sites.

PMID- 11584248
TI  - Infective endocarditis.

PMID- 11584249
TI  - Early diagnosis and treatment of prostate cancer.

PMID- 11584251
TI  - National and regional assessment of the antibacterial soap market: a step toward
      determining the impact of prevalent antibacterial soaps.
AB  - BACKGROUND: Consumer antibacterial soaps contain triclosan or triclocarban. No
      scientific data have been published to suggest that the use of antibacterial
      agents in household products prevents infection, and triclosan resistance
      mechanisms have recently been identified. Little data are available regarding the
      prevalence of antibacterial agents contained in consumer soaps. METHODS: In a
      physician-performed survey of 23 stores in 10 states from December 1999 to April
      2000, investigators determined the number of national brand liquid and bar soaps
      and percent of each containing antibacterial agents sold at national chain,
      regional grocery, and Internet stores. RESULTS: Antibacterial agents were present
      in 76% of liquid soaps and 29% of bar soaps available nationally. There were no
      differences found between national, regional, and Internet stores. CONCLUSION:
      Overall, 45% of surveyed soaps contain antibacterial agents. With limited
      documented benefits and experimental laboratory evidence suggesting possible
      adverse effects on the emergence of antimicrobial resistance, consumer
      antibacterial use of this magnitude should be questioned.

PMID- 11584252
TI  - Outbreak of Acinetobacter baumannii in an intensive care unit associated with
      tracheostomy.
AB  - A case-control study was conducted to determine risk factors for acquisition of
      an epidemic strain of Acinetobacter baumannii in an intensive care unit. The
      epidemic strain was identified by pulsed-field gel electrophoresis and was
      isolated from tracheal secretions in 13 (87%) of 15 patients. In a logistic
      regression analysis, presence of a tracheostomy was an independent risk for
      Acinetobacter sp acquisition (odds ratio, 421; 95% confidence interval, 13.8
      12925; P =.001) and the strength of the association was inversely related to the
      duration of mechanical ventilation. The outbreak coincided with the introduction
      of a policy of early percutaneous tracheostomy in the intensive care unit and
      probably resulted from inadequate infection control practices during respiratory
      care. No environmental reservoir was found. Institution of contact precautions,
      enhanced handwashing, and staff education was associated with resolution of the
      outbreak.

PMID- 11584253
TI  - Efficacy of surveillance in nosocomial infection control in a surgical service.
AB  - OBJECTIVE: The purpose of this study was to assess the efficacy of surveillance
      of nosocomial infection in infection control at a service of general surgery.
      DESIGN: A surveillance study that included 1483 patients with a prospective
      identification of nosocomial infection was carried out. Its results were
      discussed with the staff, and a program on nosocomial infection control was
      implemented. One year after the pre-intervention study, a similar study that
      included 1506 patients was done. The main outcome measure was nosocomial
      infection. Incidence rates, incidence rate ratios, crude and multiple-risk factor
      adjusted for by Poisson regression analysis, and their 95% confidence interval
      rates were estimated. RESULTS: The characteristics of the patients enrolled in
      both studies were compared. After the intervention, the trend was to attend
      patients with more severe conditions: higher frequency of liver failure, chronic
      obstructive lung disease, higher proportion of dirty surgical wounds, and higher
      scores of both Study on the Efficacy of Nosocomial Infection Control (SENIC) and
      National Nosocomial Infections Surveillance indices. There were no significant
      differences in emergency surgery, duration of surgery, age, and sex. After the
      intervention, unnecessary chemoprophylaxis was drastically reduced, and a
      significant reduction in preoperative stay was observed. The nosocomial incidence
      rate fell from 18.4 to 14 per 1000 patient-days. This reduction yielded an
      incidence rate ratio of 0.56 (95% confidence interval, 0.43%-0.74%) adjusted for
      several variables (SENIC index, serum creatinine level, serum albumin level,
      antihistamine H2 level, surgical wound, body mass index, chemoprophylaxis, and
      community-acquired infection). Significant reductions in surgical site infection
      and urinary tract infection were observed, but the rate of respiratory tract
      infection remained unchanged. CONCLUSIONS: Surveillance was effective in reducing
      nosocomial infection.

PMID- 11584254
TI  - Knowledge and performance of the universal precautions by nursing and medical
      students in Korea.
AB  - BACKGROUND: Like the health care workers, nursing and medical students have to go
      through clinical practices; accordingly, they run a high risk of being exposed to
      bloodborne diseases. But there are few studies on the realities of preventive
      education or measures to be taken after exposure to such diseases. The purpose of
      this study was to identify a knowledge of universal precautions and their
      performance in practice among the nursing and medical students in Korea. METHOD:
      This study was based on survey questionnaires with a total of 714 nursing and
      medical students for the period between November 2, 1998, and April 30, 2000.
      RESULTS: The average knowledge level of the universal precautions was 267.8 +/-
      21.3 (scores ranged from 150 to 300). The knowledge level of the universal
      precautions of the nursing students (270.4 +/- 19.4) was higher than that of the
      medical students (261.0 +/- 24.4; P =.000). The average performance level of the
      universal precautions was 52.7 +/- 6.2 (scores ranged from 14 to 70). The
      students of the nursing college showed a higher performance level of the
      universal precautions (53.2 +/- 5.9; P =.002). The correlation between knowledge
      and performance of the universal precautions showed a weak and positive
      correlation (r =.317; P=.000). CONCLUSION: The study demonstrated that the
      knowledge level of the nursing students about universal precautions was
      relatively higher than that of medical students. The group that receives
      education about universal precautions has a higher level of knowledge and
      performance of the universal precautions than that group that receives no such
      education. The education about universal precautions is indispensable; it is
      desirable to raise the relative importance for the curriculum of both nursing and
      medical colleges.

PMID- 11584255
TI  - A randomized clinical trial to compare the effects of a heat and moisture
      exchanger with a heated humidifying system on the occurrence rate of ventilator
      associated pneumonia.
AB  - BACKGROUND: The purpose of this study was to compare the performance of heat and
      moisture exchanger filters with heated humidifying systems in the mechanical
      ventilator circuit on the incidence of ventilator-associated pneumonia (VAP) and
      bacterial colonization. METHOD: Two hundred and forty-three consecutive patients
      who required mechanical ventilation for 48 hours or more in the adult intensive
      care unit were randomized to either a heat and moisture exchanger (HME) or a
      heated humidifying breathing circuit. RESULTS: The VAP rate among the group with
      HME was 11.4%; the rate among the group with heated humidifying system (HHS) was
      15.8%. The difference was not statistically significant. Approximately 68% of the
      patients in the HME group had no pathogen isolated compared with 50% of the
      patients in the HHS group. This difference was statistically significant (P
      =.006). However, the distribution of the pathogens among those patients who had
      the isolated pathogens was mostly identical in the 2 groups. CONCLUSION: Even
      though the study did not find HME to be significantly advantageous over the HHS,
      in as much as VAP rate is concerned, other advantages such as reduced nurses
      workload, reduced financial cost, and better safety made HME a more favorable
      device for use in our adult intensive care unit.

PMID- 11584256
TI  - Contamination of bronchoscopes with Mycobacterium tuberculosis and successful
      sterilization by low-temperature hydrogen peroxide plasma sterilization.
AB  - BACKGROUND: The transmission of mycobacteria by bronchoscopes has been reported
      several times in the last years. To explore methods to prevent transmission of
      tuberculosis in this way, we sterilized contaminated bronchoscopes with low
      temperature hydrogen peroxide gas plasma sterilization. METHODS: Bronchoscopes
      were contaminated with Mycobacterium tuberculosis and decontaminated with a
      washer/disinfector ("normal washing"). Some were additionally disinfected with
      glutaraldehyde ("intensive washing"). Afterward the bronchoscopes were sterilized
      by low-temperature hydrogen peroxide plasma sterilization. RESULTS: After normal
      washing, 8/17 samples had positive results by culture, and 7/17 had positive
      results by nucleic acid amplification technique. After intensive washing, all
      samples had negative results by culture, and 10/25 had positive results by
      nucleic acid amplification technique; after sterilization with low-temperature
      hydrogen peroxide plasma sterilization, all samples had negative results by
      culture and nucleic acid amplification technique. CONCLUSION: Washing of
      bronchoscopes, as performed normally, is not sufficient for decontamination of
      bronchoscopes. Additional disinfection is recommended. If the nucleic acid
      amplification technique is used for diagnostic procedures, sterilization by low
      temperature hydrogen peroxide plasma sterilization is recommended to avoid false
      positive results.

PMID- 11584257
TI  - An outbreak of Serratia marcescens associated with the anesthetic agent propofol.
AB  - BACKGROUND: In October 1999, 7 patients with postoperative infections caused by
      Serratia marcescens were identified at a community hospital in Ontario, Canada.
      We describe the investigation of this outbreak. METHODS: We undertook a case
      control study to determine risk factors associated with infection. Case subjects
      consisted of patients who had undergone surgery and acquired bacteremia or wound
      infections that, when cultured, grew S marcescens. Control subjects were selected
      from the cohort of patients who underwent surgery at the same hospital during the
      outbreak period. Chart reviews were conducted for case and control subjects.
      Environmental samples were taken from medications and liquids in the operating
      rooms and from one health care professional who was involved in all the cases. S
      marcescens isolates were forwarded to a reference laboratory for pulsed field gel
      electrophoresis. RESULTS: We identified 7 case subjects and 29 control subjects.
      Five patients had bacteremia and 2 patients had wound infections. Two patients
      with bacteremia died. All patients with bacteremia or wound infections were
      exposed to a single anesthetist (anesthetist A) and were administered the
      anesthetic medication propofol. These patients were more than 40 times more
      likely to have had anesthetist A administer their anesthetic (OR 41.6, 95% CI 3.6
      1120) and 22 times more likely to have received propofol (OR 22, 95% CI 2.1-550)
      than were control subjects. None of the environmental samples or cultures from
      anesthetist A were positive for S marcescens. Six of the 7 human isolates had an
      identical pulsed field gel electrophoresis pattern, and the seventh was
      untypable. CONCLUSIONS: This outbreak of postoperative infections was very
      strongly linked to the use of propofol by one anesthetist. Health care
      professionals must follow strict aseptic techniques when using propofol and
      should review these techniques regularly.

PMID- 11584259
TI  - Infection control considerations during construction activities: land excavation
      and demolition.
AB  - Because current trends in hospital restructuring in North America, amalgamations
      and mergers, and the aging of health care facilities, the need to restructure
      physical buildings has become greater. Hospital construction carries with it
      risks to patients. One key concern is the risk of aspergillosis associated with
      hospital construction. Infection control practitioners must consider some key
      factors when addressing land excavation and building demolition, which differ in
      some ways from construction that occurs within a health care facility. The key
      factors to consider are project concept, risk assessment of patients, procedures
      and environment, air quality, routes of entry and egress, soil management,
      conducting inspections, contingency planning, housekeeping, and lines of
      cooperation and communication with various stakeholders. Considering these areas
      will help ensure that health care facility personnel and the workers have
      exercised diligence in patient care.

PMID- 11584258
TI  - Community dissemination of vancomycin-resistant Enterococcus faecium.
AB  - BACKGROUND AND OBJECTIVE: In the United States, vancomycin-resistant enterococci
      (VRE) are predominantly acquired in the hospital. The extent of dissemination of
      VRE into the community in the United States has not been examined. Our objective
      was to determine the prevalence of VRE among nonhospitalized patients. METHODS:
      We conducted a cross-sectional surveillance study in an ambulatory care clinic.
      One hundred ambulatory patients participated in the study. Measurements included
      a written questionnaire on patient demographics, clinical data, and prior
      exposure to health care settings and antibiotics; rectal swabs; pulsed-field gel
      electrophoresis; and polymerase chain reaction genotyping. RESULTS: Three of 100
      subjects (3%) were colonized with VRE, including one person who did not have any
      exposure to a health care setting or antibiotics. CONCLUSIONS: VRE was recovered
      from nonhospitalized patients. Physicians should be alert to the potential of VRE
      transmission in the ambulatory care setting.

PMID- 11584260
TI  - Electronic chart review as an aid to postdischarge surgical site surveillance:
      increased case finding.
AB  - BACKGROUND: At the University of Michigan Hospitals and Health Centers, there is
      increasing use of an electronic medical record. Because orthopedic surgeons
      dictate all outpatient visits to the patient's electronic record, total knee
      arthroplasties were chosen to determine whether the use of electronic medical
      records increased case finding. METHODS: All patients who underwent a total knee
      arthroplasty during the study period (1996-1999) were followed prospectively with
      the use of the National Nosocomial Infection Surveillance System definitions.
      Traditional surveillance methods were used to ascertain infections. In addition,
      each patient's postdischarge outpatient clinic chart was reviewed electronically
      for 1 year after operation. RESULTS: From 1996 to 1999, 555 procedures were
      performed. Overall, 25 infections were identified after operation. Seven
      infections were identified through traditional surveillance methods, which
      resulted in an average surgical site infection rate of 1.3%. The use of
      electronic chart review surveillance after discharge revealed a rate of 4.5%,
      which was significantly higher than traditional surveillance (P <.01). Eighteen
      of 25 infections (72%) would not have been identified with the use of traditional
      surveillance methods. CONCLUSION: Postdischarge electronic chart review enhanced
      case finding significantly, which resulted in a more accurate infection rate.
      Awareness should be given to the institutions' surveillance methods and intensity
      when comparing to published rates.

PMID- 11584261
TI  - A cluster of invasive aspergillosis in a bone marrow transplant unit related to
      construction and the utility of air sampling.
AB  - BACKGROUND: An investigation was launched to identify the source of a cluster of
      invasive aspergillosis in the bone marrow transplant unit (BMTU) when
      construction was taking place on the floor directly below the unit. The utility
      of air sampling for Aspergillus was examined. METHODS: Cases of Aspergillus
      colonization and infection were identified in the BMTU and in the wards adjacent
      to the construction site. Air sampling was performed in the BMTU before and after
      room and air duct cleaning and then randomly during a 6-month period, beginning 6
      months after construction ended. The results were correlated with the incidence
      of Aspergillus infections. RESULTS: The cluster of cases of invasive
      aspergillosis could not be directly linked to the construction. In the BMTU, the
      rate of Aspergillus colonization and infection during construction was 2.5 times
      higher than that for the 6 months before the construction and 2.9 times higher
      for the adjacent wards. After construction ended, the rates returned to pre
      construction rates. Two cases of invasive aspergillosis were observed in the BMTU
      during random air sampling, but the results of air sampling could not be
      correlated to cases. CONCLUSIONS: Although the cluster of cases of invasive
      aspergillosis could not be linked to the construction, the construction did
      increase the rates of Aspergillus colonization in the BMTU and adjacent wards.
      Periodic air samplings could not correlate conidia counts to invasive Aspergillus
      infection.

PMID- 11584262
TI  - The role of economic evaluation in infection control.
AB  - Given the rise in health care-related expenditures, decision-makers are
      increasingly relying on both clinical effectiveness and economic efficiency when
      making health care decisions. The field of infection control is not immune to
      this rise in cost-consciousness among health care managers. This article
      clarifies the role of economic evaluation within infection control for both the
      user and producer of economic evaluations in this field. The strengths and
      drawbacks of the several different types of economic analysis--cost minimization,
      cost-effectiveness, cost-benefit, and cost utility analysis--will be discussed.
      Additionally, the important features of two specific methods used for economic
      evaluation-decision analytic modeling and economic analysis alongside a clinical
      trial-will be outlined. Finally, the criteria by which economic analyses should
      be judged will be provided. As economic evaluation and health services research
      continue to play an increasingly important role in health care, it will be vital
      for infection control advocates to partner with individuals from diverse fields
      to give decision-makers the type of information they need to make choices.

PMID- 11584263
TI  - Computer keyboards as a risk for nosocomial infection.

PMID- 11584264
TI  - Patient attire in ambulatory surgery.

PMID- 11584265
TI  - Topical application of a new formulation of eucalyptus oil phytochemical clears
      methicillin-resistant Staphylococcus aureus infection.

PMID- 11584266
TI  - Borg proteins control septin organization and are negatively regulated by Cdc42.
AB  - The Cdc42 GTPase binds to numerous effector proteins that control cell polarity,
      cytoskeletal remodelling and vesicle transport. In many cases the signalling
      pathways downstream of these effectors are not known. Here we show that the Cdc42
      effectors Borg1 to Borg3 bind to septin GTPases. Endogenous septin Cdc10 and
      Borg3 proteins can be immunoprecipitated together by an anti-Borg3 antibody. The
      ectopic expression of Borgs disrupts normal septin organization. Cdc42 negatively
      regulates this effect and inhibits the binding of Borg3 to septins. Borgs are
      therefore the first known regulators of mammalian septin organization and provide
      an unexpected link between the septin and Cdc42 GTPases.

PMID- 11584267
TI  - Endogenous nitric oxide mechanisms mediate the stretch dependence of Ca2+ release
      in cardiomyocytes.
AB  - Stretching of cardiac muscle modulates contraction through the enhancement of the
      Ca2+ transient, but how this occurs is still not known. We found that stretching
      of myocytes modulates the elementary Ca2+ release process from ryanodine-receptor
      Ca2+-release channels (RyRCs), Ca2+ sparks and the electrically stimulated Ca2+
      transient. Stretching induces PtdIns-3-OH kinase (PI(3)K)-dependent
      phosphorylation of both Akt and the endothelial isoform of nitric oxide synthase
      (NOS), nitric oxide (NO) production, and a proportionate increase in Ca2+-spark
      frequency that is abolished by inhibiting NOS and PI(3)K. Exogenously generated
      NO reversibly increases Ca2+-spark frequency without cell stretching. We propose
      that myocyte NO produced by activation of the PI(3)K-Akt-endothelial NOS axis
      acts as a second messenger of stretch by enhancing RyRC activity, contributing to
      myocardial contractile activation.

PMID- 11584268
TI  - A flavoprotein oxidase defines a new endoplasmic reticulum pathway for
      biosynthetic disulphide bond formation.
AB  - Ero1 and Pdi1 are essential elements of the pathway for the formation of
      disulphide bonds within the endoplasmic reticulum (ER). By screening for
      alternative oxidation pathways in Saccharomyces cerevisiae, we identified ERV2 as
      a gene that when overexpressed can restore viability and disulphide bond
      formation to an ero1-1 mutant strain. ERV2 encodes a luminal ER protein of
      relative molecular mass 22,000. Purified recombinant Erv2p is a flavoenzyme that
      can catalyse O2-dependent formation of disulphide bonds. Erv2p transfers
      oxidizing equivalents to Pdi1p by a dithiol-disulphide exchange reaction,
      indicating that the Erv2p-dependent pathway for disulphide bond formation closely
      parallels that of the previously identified Ero1p-dependent pathway.

PMID- 11584269
TI  - Spatial control of the actin cytoskeleton in Drosophila epithelial cells.
AB  - The actin cytoskeleton orders cellular space and transduces many of the forces
      required for morphogenesis. Here we combine genetics and cell biology to identify
      genes that control the polarized distribution of actin filaments within the
      Drosophila follicular epithelium. We find that profilin and cofilin regulate
      actin-filament formation throughout the cell cortex. In contrast, CAP-a
      Drosophila homologue of Adenylyl Cyclase Associated Proteins-functions
      specifically to limit actin-filament formation catalysed by Ena at apical cell
      junctions. The Abl tyrosine kinase also collaborates in this process. We
      therefore propose that CAP, Ena and Abl act in concert to modulate the
      subcellular distribution of actin filaments in Drosophila.

PMID- 11584270
TI  - Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell
      viability.
AB  - Chaperone proteins are thought to promote the correct folding and assembly of
      newly synthesized proteins and to facilitate restoration of the folded state
      under environmental conditions that favour protein denaturation. They are among
      the most ubiquitous and highly conserved of all proteins. The eukaryotic
      endoplasmic reticulum (ER) chaperone gp96 in particular has long been thought to
      be indispensable for cell survival. Here we report that a screen for genes
      required for the immune response to bacterial endotoxins has identified a B-cell
      line deficient in gp96. Absence of gp96 is compatible with cellular survival even
      under stress conditions and causes a defect in the formation of only a small
      subset of cell surface receptors. Toll-like receptors are retained
      intracellularly in the absence of gp96, explaining the unresponsiveness of the
      mutant to microbial stimuli.

PMID- 11584271
TI  - N-WASP deficiency reveals distinct pathways for cell surface projections and
      microbial actin-based motility.
AB  - The Wiskott-Aldrich syndrome protein (WASP) family of molecules integrates
      upstream signalling events with changes in the actin cytoskeleton. N-WASP has
      been implicated both in the formation of cell-surface projections (filopodia)
      required for cell movement and in the actin-based motility of intracellular
      pathogens. To examine N-WASP function we have used homologous recombination to
      inactivate the gene encoding murine N-WASP. Whereas N-WASP-deficient embryos
      survive beyond gastrulation and initiate organogenesis, they have marked
      developmental delay and die before embryonic day 12. N-WASP is not required for
      the actin-based movement of the intracellular pathogen Listeria but is absolutely
      required for the motility of Shigella and vaccinia virus. Despite these distinct
      defects in bacterial and viral motility, N-WASP-deficient fibroblasts spread by
      using lamellipodia and can protrude filopodia. These results imply a crucial and
      non-redundant role for N-WASP in murine embryogenesis and in the actin-based
      motility of certain pathogens but not in the general formation of actin
      containing structures.

PMID- 11584272
TI  - Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the
      amyloid beta-peptide.
AB  - The pathogenic event common to all forms of Alzheimer's disease is the abnormal
      accumulation of the amyloid beta-peptide (Abeta). Here we provide strong evidence
      that intracellular cholesterol compartmentation modulates the generation of
      Abeta. Using genetic, biochemical and metabolic approaches, we found that
      cholesteryl-ester levels are directly correlated with Abeta production. Acyl
      coenzyme A:cholesterol acyltransferase (ACAT), the enzyme that catalyses the
      formation of cholesteryl esters, modulates the generation of Abeta through the
      tight control of the equilibrium between free cholesterol and cholesteryl esters.
      We also show that pharmacological inhibitors of ACAT, developed for the treatment
      of atherosclerosis, are potent modulators of Abeta generation, indicating their
      potential for use in the treatment of Alzheimer's disease.

PMID- 11584273
TI  - Dynein binds to beta-catenin and may tether microtubules at adherens junctions.
AB  - Interactions between microtubule and actin networks are thought to be crucial for
      mechanical and signalling events at the cell cortex. Cytoplasmic dynein has been
      proposed to mediate many of these interactions. Here, we report that dynein is
      localized to the cortex at adherens junctions in cultured epithelial cells and
      that this localization is sensitive to drugs that disrupt the actin cytoskeleton.
      Dynein is recruited to developing contacts between cells, where it localizes with
      the junctional proteins beta-catenin and E-cadherin. Microtubules project towards
      these early contacts and we hypothesize that dynein captures and tethers
      microtubules at these sites. Dynein immunoprecipitates with beta-catenin, and
      biochemical analysis shows that dynein binds directly to beta-catenin.
      Overexpression of beta-catenin disrupts the cellular localization of dynein and
      also dramatically perturbs the organization of the cellular microtubule array. In
      cells overexpressing beta-catenin, the centrosome becomes disorganized and
      microtubules no longer appear to be anchored at the cortex. These results
      identify a novel role for cytoplasmic dynein in capturing and tethering
      microtubules at adherens junctions, thus mediating cross-talk between actin and
      microtubule networks at the cell cortex.

PMID- 11584274
TI  - Extracellular control of cell size.
AB  - Both cell growth (cell mass increase) and progression through the cell division
      cycle are required for sustained cell proliferation. Proliferating cells in
      culture tend to double in mass before each division, but it is not known how
      growth and division rates are co-ordinated to ensure that cell size is
      maintained. The prevailing view is that coordination is achieved because cell
      growth is rate-limiting for cell-cycle progression. Here, we challenge this view.
      We have investigated the relationship between cell growth and cell-cycle
      progression in purified rat Schwann cells, using two extracellular signal
      proteins that are known to influence these cells. We find that glial growth
      factor (GGF) can stimulate cell-cycle progression without promoting cell growth.
      We have used this restricted action of GGF to show that, for cultured Schwann
      cells, cell growth rate alone does not determine the rate of cell-cycle
      progression and that cell size at division is variable and depends on the
      concentrations of extracellular signal proteins that stimulate cell-cycle
      progression, cell growth, or both.

PMID- 11584275
TI  - Three-dimensional reconstruction of dynamin in the constricted state.
AB  - Members of the dynamin family of GTPases have unique structural properties that
      might reveal a general mechanochemical basis for membrane constriction. Receptor
      mediated endocytosis, caveolae internalization and certain trafficking events in
      the Golgi all require dynamin for vesiculation. The dynamin-related protein Drp1
      (Dlp1) has been implicated in mitochondria fission and a plant dynamin-like
      protein phragmoplastin is involved in the vesicular events leading to cell wall
      formation. A common theme among these proteins is their ability to self-assemble
      into spirals and their localization to areas of membrane fission. Here we present
      the first three-dimensional structure of dynamin at a resolution of approximately
      20 A, determined from cryo-electron micrographs of tubular crystals in the
      constricted state. The map reveals a T-shaped dimer consisting of three prominent
      densities: leg, stalk and head. The structure suggests that the dense stalk and
      head regions rearrange when GTP is added, a rearrangement that generates a force
      on the underlying lipid bilayer and thereby leads to membrane constriction. These
      results indicate that dynamin is a force-generating 'contrictase'.

PMID- 11584276
TI  - Endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP.
AB  - Intersectin-s is a modular scaffolding protein regulating the formation of
      clathrin-coated vesicles. In addition to the Eps15 homology (EH) and Src homology
      3 (SH3) domains of intersectin-s, the neuronal variant (intersectin-l) also has
      Dbl homology (DH), pleckstrin homology (PH) and C2 domains. We now show that
      intersectin-l functions through its DH domain as a guanine nucleotide exchange
      factor (GEF) for Cdc42. In cultured cells, expression of DH-domain-containing
      constructs cause actin rearrangements specific for Cdc42 activation. Moreover, in
      vivo studies reveal that stimulation of Cdc42 by intersectin-l accelerates actin
      assembly via N-WASP and the Arp2/3 complex. N-WASP binds directly to intersectin
      l and upregulates its GEF activity, thereby generating GTP-bound Cdc42, a
      critical activator of N-WASP. These studies reveal a role for intersectin-l in a
      novel mechanism of N-WASP activation and in regulation of the actin cytoskeleton.

PMID- 11584277
TI  - Drosophila APC2 and Armadillo participate in tethering mitotic spindles to
      cortical actin.
AB  - Proper positioning of mitotic spindles ensures equal allocation of chromosomes to
      daughter cells. This often involves interactions between spindle and astral
      microtubules and cortical actin. In yeast and Caenorhabditis elegans, some of the
      protein machinery that connects spindles and cortex has been identified but, in
      most animal cells, this process remains mysterious. Here, we report that the
      tumour suppressor homologue APC2 and its binding partner Armadillo both play
      roles in spindle anchoring during the syncytial mitoses of early Drosophila
      embryos. Armadillo, alpha-catenin and APC2 all localize to sites of cortical
      spindle attachment. APC2-Armadillo complexes often localize with interphase
      microtubules. Zeste-white 3 kinase, which can phosphorylate Armadillo and APC, is
      also crucial for spindle positioning and regulates the localization of APC2
      Armadillo complexes. Together, these data suggest that APC2, Armadillo and alpha
      catenin provide an important link between spindles and cortical actin, and that
      this link is regulated by Zeste-white 3 kinase.

PMID- 11584279
TI  - Declaration of financial interests.

PMID- 11584278
TI  - Proteins containing the UBA domain are able to bind to multi-ubiquitin chains.
AB  - The UBA domain is a motif found in a variety of proteins, some of which are
      associated with the ubiquitin-proteasome system. We describe the isolation of a
      fission-yeast gene, mud1+, which encodes a UBA domain containing protein that is
      able to bind multi-ubiquitin chains. We show that the UBA domain is responsible
      for this activity. Two other proteins containing this motif, the fission-yeast
      homologues of Rad23 and Dsk2, are also shown to bind multi-ubiquitin chains via
      their UBA domains. These two proteins are implicated, along with the fission
      yeast Pus1(S5a/Rpn10) subunit of the 26 S proteasome, in the recognition and
      turnover of substrates by this proteolytic complex.

PMID- 11584280
TI  - Presenilins and the intramembrane proteolysis of proteins: facts and fiction.

PMID- 11584281
TI  - Catch and pull a microtubule: getting a grasp on the cortex.

PMID- 11584282
TI  - Moving on up and down.

PMID- 11584283
TI  - Sugar-coated pathways for developmental patterning.

PMID- 11584284
TI  - Genetics still moving forward.

PMID- 11584285
TI  - Ubiquitination, proteasomes and GABA(A) receptors.

PMID- 11584289
TI  - Molecular chaperone targeting and regulation by BAG family proteins.
AB  - Regulated changes in protein conformation can have profound effects on protein
      function, although routine laboratory methods often fail to detect them. The
      recently discovered BAG-family proteins may operate as bridging molecules that
      recruit molecular chaperones to target proteins, presumably modulating protein
      functions through alterations in their conformations, and ultimately affecting
      diverse cellular behaviours including cell division, migration, differentiation
      and death. Emerging knowledge about BAG-family proteins indicates that there may
      be a mechanism for influencing signal transduction through non-covalent post
      translational modifications.

PMID- 11584290
TI  - Adaptation to three-dimensional distortions in human vision.

PMID- 11584291
TI  - Conditional control of gene expression in the mouse.
AB  - One of the most powerful tools that the molecular biology revolution has given us
      is the ability to turn genes on and off at our discretion. In the mouse, this has
      been accomplished by using binary systems in which gene expression is dependent
      on the interaction of two components, resulting in either transcriptional
      transactivation or DNA recombination. During recent years, these systems have
      been used to analyse complex and multi-staged biological processes, such as
      embryogenesis and cancer, with unprecedented precision. Here, I review these
      systems and discuss certain studies that exemplify the advantages and limitations
      of each system.

PMID- 11584292
TI  - Gene-trap mutagenesis: past, present and beyond.
AB  - Although at least 35,000 human genes have been sequenced and mapped, adequate
      expression or functional information is available for only approximately 15% of
      them. Gene-trap mutagenesis is a technique that randomly generates loss-of
      function mutations and reports the expression of many mouse genes. At present,
      several large-scale, gene-trap screens are being carried out with various new
      vectors, which aim to generate a public resource of mutagenized embryonic stem
      (ES) cells. This resource now includes more than 8,000 mutagenized ES-cell lines,
      which are freely available, making it an appropriate time to evaluate the recent
      advances in this area of genomic technology and the technical hurdles it has yet
      to overcome.

PMID- 11584293
TI  - Recombineering: a powerful new tool for mouse functional genomics.
AB  - Highly efficient phage-based Escherichia coli homologous recombination systems
      have recently been developed that enable genomic DNA in bacterial artificial
      chromosomes to be modified and subcloned, without the need for restriction
      enzymes or DNA ligases. This new form of chromosome engineering, termed
      recombinogenic engineering or recombineering, is efficient and greatly decreases
      the time it takes to create transgenic mouse models by traditional means.
      Recombineering also facilitates many kinds of genomic experiment that have
      otherwise been difficult to carry out, and should enhance functional genomic
      studies by providing better mouse models and a more refined genetic analysis of
      the mouse genome.

PMID- 11584294
TI  - Engineering chromosomal rearrangements in mice.
AB  - The combination of gene-targeting techniques in mouse embryonic stem cells and
      the Cre/loxP site-specific recombination system has resulted in the emergence of
      chromosomal-engineering technology in mice. This advance has opened up new
      opportunities for modelling human diseases that are associated with chromosomal
      rearrangements. It has also led to the generation of visibly marked deletions and
      balancer chromosomes in mice, which provide essential reagents for maximizing the
      efficiency of large-scale mutagenesis efforts and which will accelerate the
      functional annotation of mammalian genomes, including the human genome.

PMID- 11584295
TI  - Segmental duplications: an 'expanding' role in genomic instability and disease.
AB  - The knowledge that specific genetic diseases are caused by recurrent chromosomal
      aberrations has indicated that genomic instability might be directly related to
      the structure of the regions involved. The sequencing of the human genome has
      directed significant attention towards understanding the molecular basis of such
      recombination 'hot spots'. Segmental duplications have emerged as a significant
      factor in the aetiology of disorders that are caused by abnormal gene dosage.
      These observations bring us closer to understanding the mechanisms and
      consequences of genomic rearrangement.

PMID- 11584296
TI  - A tour of structural genomics.
AB  - Structural genomics projects aim to provide an experimental or computational
      three-dimensional model structure for all of the tractable macromolecules that
      are encoded by complete genomes. To this end, pilot centres worldwide are now
      exploring the feasibility of large-scale structure determination. Their
      experimental structures and computational models are expected to yield insight
      into the molecular function and mechanism of thousands of proteins. The
      pervasiveness of this information is likely to change the use of structure in
      molecular biology and biochemistry.

PMID- 11584297
TI  - What is 'public opinion' about genetics?
AB  - Every biotechnology success story increases the number of decisions that the lay
      public must make about genetics. But vibrant public discussion about these far
      reaching changes has been rare, and research on the public's understanding of
      genetics has barely scratched the surface. This article reviews what we know
      about the public's attitudes towards genetics, proposes some concepts for
      thinking about public involvement and indicates some future lines of research.

PMID- 11584298
TI  - Green revolution: the way forward.
AB  - The origin of agriculture led to the domestication of many plant species and to
      the exploitation of natural resources. It took almost 10,000 years for food grain
      production to reach 1 billion tons, in 1960, and only 40 years to reach 2 billion
      tons, in 2000. This unprecedented increase, which has been named the 'green
      revolution', resulted from the creation of genetically improved crop varieties,
      combined with the application of improved agronomic practices.

PMID- 11584299
TI  - The endocytic pathway: a mosaic of domains.
AB  - Organelles in the endocytic pathway are composed of a mosaic of structural and
      functional regions. These regions consist, at least in part, of specialized
      protein-lipid domains within the plane of the membrane, or of protein complexes
      associated with specific membrane lipids. Whereas some of these molecular
      assemblies can be found in more than one compartment, a given combination seems
      to be unique to each compartment, indicating that membrane organization might be
      modular.

PMID- 11584300
TI  - The INK4a/ARF network in tumour suppression.
AB  - The retinoblastoma protein (RB) and p53 transcription factor are regulated by two
      distinct proteins that are encoded by the INK4a/ARF locus. Genes encoding these
      four tumour suppressors are disabled, either in whole or in part, in most human
      cancers. A complex signalling network that interconnects the activities of RB and
      p53 monitors oncogenic stimuli to provide a cell-autonomous mode of tumour
      surveillance.

PMID- 11584301
TI  - The melanosome: membrane dynamics in black and white.
AB  - Melanosomes are morphologically and functionally unique organelles within which
      melanin pigments are synthesized and stored. Melanosomes share some
      characteristics with lysosomes, but can be distinguished from them in many ways.
      The biogenesis and intracellular movement of melanosomes and related organelles
      are disrupted in several genetic disorders in mice and humans. The recent
      characterization of genes defective in these diseases has reinvigorated interest
      in the melanosome as a model system for understanding the molecular mechanisms
      that underlie intracellular membrane dynamics.

PMID- 11584302
TI  - A decade of CDK5.
AB  - Since it was identified a decade ago, cyclin-dependent kinase 5 (CDK5) has
      emerged as a crucial regulator of neuronal migration in the developing central
      nervous system. CDK5 phosphorylates a diverse list of substrates, implicating it
      in the regulation of a range of cellular processes - from adhesion and motility,
      to synaptic plasticity and drug addiction. Recent evidence indicates that
      deregulation of this kinase is involved in the pathology of neurodegenerative
      diseases.

PMID- 11584303
TI  - PKB/AKT: functional insights from genetic models.
AB  - Since its discovery 10 years ago, the potential functions of protein kinase B
      (PKB)/AKT have been catalogued with increasing efficiency. The physiological
      relevance of some of the proposed mechanisms by which PKB/AKT mediates many of
      its effects has been questioned, and recent work using new reagents and
      approaches has revealed some cracks in our understanding of this important
      molecule, and also hinted that these effects may involve other players.

PMID- 11584304
TI  - The renaissance of GSK3.
AB  - Glycogen synthase kinase 3 (GSK3) was initially described as a key enzyme
      involved in glycogen metabolism, but is now known to regulate a diverse array of
      cell functions. The study of the substrate specificity and regulation of GSK3
      activity has been important in the quest for therapeutic intervention.

PMID- 11584305
TI  - Giulio Bizzozero: a pioneer of cell biology.
AB  - The Italian pathologist Giulio Bizzozero began his haematological investigations
      more than 130 years ago. Among his outstanding achievements was the discovery of
      the role of platelets in haemostasis and the identification of the bone marrow as
      the site of production of blood cells. One hundred years after his untimely
      death, the significance of these, and many more of his findings, is still
      recognized.

PMID- 11584306
TI  - Searching for a baseline: functional imaging and the resting human brain.
AB  - Functional brain imaging in humans has revealed task-specific increases in brain
      activity that are associated with various mental activities. In the same studies,
      mysterious, task-independent decreases have also frequently been encountered,
      especially when the tasks of interest have been compared with a passive state,
      such as simple fixation or eyes closed. These decreases have raised the
      possibility that there might be a baseline or resting state of brain function
      involving a specific set of mental operations. We explore this possibility,
      including the manner in which we might define a baseline and the implications of
      such a baseline for our understanding of brain function.

PMID- 11584307
TI  - Addiction and the brain: the neurobiology of compulsion and its persistence.
AB  - People take addictive drugs to elevate mood, but with repeated use these drugs
      produce serious unwanted effects, which can include tolerance to some drug
      effects, sensitization to others, and an adapted state - dependence - which sets
      the stage for withdrawal symptoms when drug use stops. The most serious
      consequence of repetitive drug taking, however, is addiction: a persistent state
      in which compulsive drug use escapes control, even when serious negative
      consequences ensue. Addiction is characterized by a long-lasting risk of relapse,
      which is often initiated by exposure to drug-related cues. Substantial progress
      has been made in understanding the molecular and cellular mechanisms of
      tolerance, dependence and withdrawal, but as yet we understand little of the
      neural substrates of compulsive drug use and its remarkable persistence. Here we
      review evidence for the possibility that compulsion and its persistence are based
      on a pathological usurpation of molecular mechanisms that are normally involved
      in memory.

PMID- 11584308
TI  - Dynamic predictions: oscillations and synchrony in top-down processing.
AB  - Classical theories of sensory processing view the brain as a passive, stimulus
      driven device. By contrast, more recent approaches emphasize the constructive
      nature of perception, viewing it as an active and highly selective process.
      Indeed, there is ample evidence that the processing of stimuli is controlled by
      top-down influences that strongly shape the intrinsic dynamics of thalamocortical
      networks and constantly create predictions about forthcoming sensory events. We
      discuss recent experiments indicating that such predictions might be embodied in
      the temporal structure of both stimulus-evoked and ongoing activity, and that
      synchronous oscillations are particularly important in this process. Coherence
      among subthreshold membrane potential fluctuations could be exploited to express
      selective functional relationships during states of expectancy or attention, and
      these dynamic patterns could allow the grouping and selection of distributed
      neuronal responses for further processing.

PMID- 11584309
TI  - A neurocognitive perspective on language: the declarative/procedural model.
AB  - What are the psychological, computational and neural underpinnings of language?
      Are these neurocognitive correlates dedicated to language? Do different parts of
      language depend on distinct neurocognitive systems? Here I address these and
      other issues that are crucial for our understanding of two fundamental language
      capacities: the memorization of words in the mental lexicon, and the rule
      governed combination of words by the mental grammar. According to the
      declarative/procedural model, the mental lexicon depends on declarative memory
      and is rooted in the temporal lobe, whereas the mental grammar involves
      procedural memory and is rooted in the frontal cortex and basal ganglia. I argue
      that the declarative/procedural model provides a new framework for the study of
      lexicon and grammar.

PMID- 11584310
TI  - Classical and new roles of beta-arrestins in the regulation of G-protein-coupled
      receptors.
AB  - In the classical model of G-protein-coupled receptor (GPCR) regulation, arrestins
      terminate receptor signalling. After receptor activation, arrestins desensitize
      phosphorylated GPCRs, blocking further activation and initiating receptor
      internalization. This function of arrestins is exemplified by studies on the role
      of arrestins in the development of tolerance to, but not dependence on, morphine.
      Arrestins also link GPCRs to several signalling pathways, including activation of
      the non-receptor tyrosine kinase SRC and mitogen-activated protein kinase. In
      these cascades, arrestins function as adaptors and scaffolds, bringing
      sequentially acting kinases into proximity with each other and the receptor. The
      signalling roles of arrestins have been expanded even further with the discovery
      that the formation of stable receptor-arrestin complexes initiates photoreceptor
      apoptosis in Drosophila, leading to retinal degeneration. Here we review our
      current understanding of arrestin function, discussing both its classical and
      newly discovered roles.

PMID- 11584311
TI  - Cytokines and acute neurodegeneration.
AB  - Cytokines have been implicated as mediators and inhibitors of diverse forms of
      neurodegeneration. They are induced in response to brain injury and have diverse
      actions that can cause, exacerbate, mediate and/or inhibit cellular injury and
      repair. Here we review evidence for the contribution of cytokines to acute
      neurodegeneration, focusing primarily on interleukin 1 (IL-1), tumour necrosis
      factor-alpha (TNFalpha) and transforming growth factor-beta (TGFbeta). TGFbeta
      seems to exert primarily neuroprotective actions, whereas TNFalpha might
      contribute to neuronal injury and exert protective effects. IL-1 mediates
      ischaemic, excitotoxic and traumatic brain injury, probably through multiple
      actions on glia, neurons and the vasculature. Understanding cytokine action in
      acute neurodegeneration could lead to novel and effective therapeutic strategies,
      some of which are already in clinical trials.

PMID- 11584312
TI  - Interventional strategies against prion diseases.
AB  - Only a few years ago, the idea that transmissible spongiform encephalopathies
      could be treated pharmacologically would have met with considerable scepticism.
      Even now, there is no way to cure a patient or animal suffering from a manifest
      prion disease. But recent, exciting developments seem to indicate that
      immunological and pharmacological interventions could have some potential for the
      pre-exposure and post-exposure prophylaxis of prion diseases. Although it is
      unlikely that we will be able to cure the clinically overt stages of prion
      diseases in the foreseeable future, palliative and even life-prolonging
      interventions might no longer be confined to the realm of science fiction.

PMID- 11584314
TI  - Type 1 protein tyrosine kinases in Chinese breast carcinomas: a clinicopathologic
      study.
AB  - Immunostaining for epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3, c
      erbB-4, ER, and PR was performed in 107 cases of primary breast carcinomas from
      Anyang, China. The expression rates of EGFR, c-erbB-2, c-erbB-3 and c-erbB-4 in
      this series were 43.9%, 36%, 27%, and 45.8%, respectively, and a stronger c-erbB
      4 staining of "normal" glandular structures inside tumors and in the vicinity of
      tumor clusters was confirmed. Larger tumor size, lymph node metastases, and
      higher histologic grade in invasive ductal carcinomas were shown to be
      statistically valuable negative prognostic factors, and c-erbB-2 expression was
      also weakly associated with a poor prognosis no matter what the nodal status. The
      expressions of c-erbB-4 and ER in invasive ductal carcinomas were inversely
      associated with histologic grade of the tumors. Associations between the
      expression of c-erbB-4 and ER (p = 0.001) and the expression of ER and PR study
      (p = 0.004) were found in the present study. No significant associations between
      the expressions of EGFR, c-erbB-3, c-erbB-4, ER, and PR and overall survival were
      detected. The expression of c-erbB-4 in the node negative group was, however,
      associated with a better prognosis, indicating a different role of c-erbB-4
      protein in breast tumor development than other EGFR family members have. Int J
      Surg Pathol 9(3):177-187, 2001

PMID- 11584316
TI  - Atypical cystic lobules in patients with lobular neoplasia.
AB  - We analyzed the frequency and anatomic distribution of atypical cystic lobules
      (ACLs) in patients whose index biopsy specimen contained lobular neoplasia (LN).
      Thirty of 54 patients (56%) had ACLs in their index biopsy specimen. Five of the
      patients whose index biopsy lacked ACLs underwent an additional biopsy, and 4 of
      these patients had ACLs in an additional specimen, bringing the total number of
      patients having both ACLs and LN to 34 of 54 (62.9%). ACLs involved both breasts
      with equal frequency and neither the extent of the involvement nor the anatomic
      location of the LN paralleled the distribution of the ACLs. The presence of ACLs
      in patients with LN might explain its increased risk for the development of
      ductal carcinomas and their bilateral distribution. Int J Surg Pathol 9(3):201
      206, 2001

PMID- 11584315
TI  - Giant cell reparative granuloma: a comparative clinicopathologic study of lesions
      in gnathic and extragnathic sites.
AB  - This study attempts to define the clinicopathologic aspects of extragnathic giant
      cell reparative granuloma (GCRG) by contrasting it with the much better
      recognized GCRG of jaw bones and highlights the manifestations that are unique to
      the extragnathic localization. Ninety-one GCRGs of 89 patients, 22 in jaw bones
      and 69 in the extragnathic bones, were examined. Females were affected twice as
      frequently as males in both groups. The age distribution of extragnathic GCRGs
      overlaps that of gnathic counterparts. Small bones of the hands (17 lesions) and
      feet (16 lesions) were the most common sites for extragnathic lesions. The
      radiographic findings were nonspecific. Histology of extragnathic lesions was
      closely similar to that of lesions affecting the jaw. These giant cell lesions
      should be distinguished from giant cell tumors. Int J Surg Pathol 9(3):189-200,
      2001

PMID- 11584317
TI  - Inflammatory pseudotumor of lymph nodes: clinicopathologic and immunohistological
      study of 11 Japanese cases.
AB  - We report 11 Japanese cases of inflammatory pseudotumor (IPT) of the lymph node.
      There were 7 males and 4 females with ages ranging from 5 to 68 years (median;
      48). Only 2 patients had systemic lymphadenopathy, and all others had involvement
      of only 1 lymph node group. Constitutional symptoms such as fever were present in
      8 patients and laboratory abnormalities were detected in 5. All patients
      recovered and were alive and well after 2 to 180 months (median; 32 months).
      Histologically, the process mainly involved the connective tissue framework of
      the lymph node, secondarily spreading into the lymph node parenchyma and the
      perinodal tissue. It was characterized by a storiform growth pattern of
      myofibroblasts, marked vascularity with associated vascular lesions, and a
      polymorphous reactive cellular infiltrate in a collagen-rich stroma. An
      immunohistochemical study revealed numerous myofibroblasts, histiocytes, and
      vascular endothelial cells expressing vascular endothelial growth factor (VEGF)
      in 6 cases. It was suggested that VEGF may be involved, in part, in the induction
      of the angiogenesis of IPT. Moreover, the present study indicates that follicular
      dendritic cell sarcoma, nasal T/natural killer cell lymphoma, and anaplastic
      large cell lymphoma should be added to the differential diagnosis from IPT of the
      lymph node. Int J Surg Pathol 9(3):207-214, 2001

PMID- 11584318
TI  - Small cell variant of renal oncocytoma--a rare and misleading type of benign
      renal tumor.
AB  - Here we report 3 cases of renal oncocytoma with a dominating small cell component
      arising in adult women. These 3 cases of small cell variant of renal oncocytoma
      were found among 134 cases of oncocytomas of the kidney in the routine and
      consultation files of the authors. Two of 3 cases were initially thought to be a
      malignant tumor by the referring pathologists. In all 3 cases minor areas of the
      tumors, which were identical to the classical renal oncocytomas were found. The
      small cell areas were arranged in a characteristic organoid pattern different
      from all the known types of the renal benign and malignant tumors. We summarize
      all morphologic, immunohistochemical, and ultrastructural features of this
      unusual oncocytoma variant with regard to its differential diagnosis. Int J Surg
      Pathol 9(3):215-222, 2001

PMID- 11584321
TI  - Diagnostic errors in surgical pathology uncovered by a review of malpractice
      claims: part VI--urinary bladder and branchial cleft cyst.

PMID- 11584322
TI  - The career and influence of Pierre Masson (1880-1959).

PMID- 11584323
TI  - Infiltrating ductal carcinoma of the breast with rhabdoid phenotype.
AB  - Two cases of ductal cancers of the breast of no special type with a prominent
      rhabdoid component are presented. The mastectomy specimens showed the tumors to
      be composed of cells with a characteristic rhabdoid phenotype: Large cells with
      eccentric nuclei containing large inclusion like nucleoli and abundant
      eosinophilic cytoplasm. Immunohistochemistry showed typical immunoreactivity with
      cytoplasmic dot-like accentuation for epithelial markers as well as vimentin. In
      case 1, although excision margins were clear, tumor recurrence, composed mainly
      of rhabdoid cells, occurred within 7 months, and the patient died 2 months later.
      The second case, unfortunately, was lost to follow-up. This report is the second
      documenting the occurrence of rhabdoid cells in breast cancer. In keeping with
      other epithelial malignancies that contain rhabdoid cells, aggressive biological
      behavior is noted. Int J Surg Pathol 9(3):237-239, 2001

PMID- 11584324
TI  - Metastatic metanephric adenoma with foci of papillary carcinoma in a child: a
      combined histologic, immunohistochemical, and FISH study.
AB  - We report an example of metastatic metanephric adenoma containing foci of
      papillary carcinoma in the primitive tumor arising in the left kidney of an 11
      year-old girl. Histology revealed a monomorphous population of small cells with
      bland cytology arranged in pseudoglandular, tubular, papillary, and glomeruloid
      structures with frequent psammoma bodies. Intermixed there were foci of and small
      cavities lined by larger cells with eosinophilic cytoplasm and larger nuclei with
      small nucleoli. A regional lymph node contained metastatic deposits with the
      former histologic pattern. By immunohistochemistry the small cells were negative
      for carcinoembryonic antigen (CEA) and keratin 7 while these antibodies reacted
      positively in the larger cells. A fluorescent in-situ hybridization (FISH) study
      for chromosome 17 in imprints from the primitive tumor revealed 3 signals in
      about 10% of the nuclei while the rest was disomic. Disaggregated cells from the
      metastatic lymph node consistently revealed 2 signals for chromosomes 7, 16, and
      l7. Histology of the primitive tumor resembled the epithelial component of the so
      called metanephric adenofibroma while the metastatic lymph node exhibited
      histologic and FISH genomic features of metanephic adenoma. Int J Surg Pathol
      9(3):241-247, 2001

PMID- 11584325
TI  - Calcifying fibrous pseudotumor of mesentery presenting with acute peritonitis:
      case report with immunohistochemical study and review of literature.
AB  - Calcifying fibrous pseudotumor (CFP) is a benign soft tissue lesion composed of
      thick collagen bundles, scattered fibroblasts, and psammomatous and dystrophic
      calcifications, located most commonly in the extremities and trunk of children
      and young adults. The present case in a 36-year-old woman is to the best of our
      knowledge the first report of a large CFP confined to the mesentery, which,
      because of torsion, led to acute peritonitis and emergency laparotomy. The
      typical histologic features were accompanied by a prominent myofibroblastic
      proliferation along with inflammatory response at the periphery of the lesion.
      The spindle cells of the lesion were positive for vimentin and focally for CD34
      and smooth-muscle actin. Review of the literature and discussion of differential
      diagnosis in this report focuses on abdominal CFP and other intraabdominal soft
      tissue lesions, some of which may be precursors of CFP. Int J Surg Pathol
      9(3):249-253, 2001

PMID- 11584326
TI  - Malignant granular cell tumor of soft tissues: a study of two new cases.
AB  - We describe 2 cases of malignant granular cell tumor. A marked discrepancy exists
      concerning the criteria of malignancy of this rare entity, which was diagnosed in
      male patients aged 41 and 52 years, respectively. They presented with tumors
      measuring more then 3.5 cm; one arose in the dermis and subcutaneous tissue in
      the region of the scapula, whereas the other was situated in deeper soft tissue
      in the pelvis. One case, with previous diagnosis of benign granular cell tumor,
      presented local recurrence 2 years after the initial diagnosis. The other case
      presented a fascicular pattern of growth invading adjacent muscular tissue. Both
      neoplasms were composed of polygonal and spindle cells, showing abundant
      cytoplasm, vesicular nuclei with large nucleoli, high nuclear-to-cytoplasmic
      ratio, and pleomorphism. Immunohistochemically, the neoplastic cells of both
      cases were positive for vimentin, S100 protein, neuron-specific enolase (NSE),
      and CD68. In addition, high expression of p53 and MiB1 (Ki67) was detected.
      Herein, we discuss the morphologic and immunohistochemical criteria of malignancy
      of granular cell tumors. Int J Surg Pathol 9(3):255-259, 2001

PMID- 11584327
TI  - Prevention of ventricular fibrillation during acute myocardial ischemia: control
      of free fatty acids.
AB  - Fatal ventricular fibrillation is a common complication of acute coronary
      syndromes. Effective preventive measures are not available. Immediate restriction
      of free fatty acid availability should optimize ischemic myocardial metabolism,
      reduce ventricular vulnerability, and increase glucose utilization. Rapid
      inhibition of lipoprotein lipase activity will achieve this. The clinical effects
      of antilipolytic treatment require further study.

PMID- 11584328
TI  - Treatment of the elderly with 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors: focus on drug interactions.
AB  - With the aging of the population, death from coronary heart disease (CHD) and
      stroke has become more prevalent. Cardiovascular disease (CVD) risk factors, such
      as hypertension, obesity, and diabetes mellitus increase with age as well. Recent
      secondary-prevention studies have established the positive effect of statins in
      decreasing the risk of CHD mortality through the lowering of cholesterol. Statins
      have an excellent safety record, at least with users under age 65, and provide a
      cheaper alternative to more costly medical options. The most serious side effect
      associated with their use is myopathy, which is infrequent. Drug interactions
      have been found with drugs that compete for the same CYP450 isoenzymes as
      statins. Several drugs have been shown to significantly inhibit the CYP3A4
      pathway; in combination with statins such as lovastatin, simvastatin,
      atorvastatin, and cerivastatin, they have been shown to elevate serum
      concentrations of these statins, or may increase the risk of myopathy.
      Alternatively, other drugs can inhibit the CYP2C9 pathway and may elevate serum
      concentration of fluvastatin. Due to the number of medications the elderly
      receive, an understanding of the various metabolic pathways is of vital
      importance to minimize the potential for drug interactions. The elderly
      population, while at high risk for CVD, is currently undertreated. Statins can
      effectively lower low-density lipoprotein cholesterol levels and lessen the risk
      of CVD for this population.

PMID- 11584329
TI  - Ventricular free wall rupture in acute myocardial infarction.
AB  - Despite a progressive reduction in acute myocardial infarction mortality over the
      years, death related to ventricular free wall rupture has not changed. This is
      mostly related to the catastrophic presentation and death within minutes in the
      majority of these patients. Once rupture is suspected, bedside echocardiography
      should be performed immediately, followed by pericardiocentesis and repair of the
      rupture site as quickly as possible. Measures to prevent cardiac rupture include
      the administration of beta-blockers and angiotensin-converting enzyme inhibitors
      unless contraindications exist, and the avoidance of steroidal and nonsteroidal
      anti-inflammatory agents such as ibuprofen and indomethacin.

PMID- 11584330
TI  - Electrophysiologic effects of a novel selective adenosine A1 agonist (CVT-510) on
      atrioventricular nodal conduction in humans.
AB  - BACKGROUND: CVT-510, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside, is a
      selective A(1)-adenosine receptor agonist with potential potent antiarrhythmic
      effects in tachycardias involving the atrioventricular (AV) node. This study, the
      first in humans, was designed to determine the effects of CVT-510 on AV nodal
      conduction and hemodynamics. METHODS AND RESULTS: Patients in sinus rhythm with
      normal AV nodal function at electrophysiologic study (n = 32) received a single
      intravenous bolus of CVT-510. AH and HV intervals were measured during sinus
      rhythm and during atrial pacing at 1, 5, 10, 15, 20, 30, 45, and 60 minutes after
      the bolus. Increasing doses of CVT-510 (0.3 to 10 microg/kg) caused a dose
      dependent increase in the AH interval. At 1 minute, a dose of 10 microg/kg
      increased the AH interval during sinus rhythm from 93 +/- 23 msec to 114 +/- 37
      msec, p = 0.01 and from 114 +/- 31 msec to 146 +/- 44 msec during atrial pacing
      at 600 msec, p = 0.003). The AH interval returned to baseline by 20 minutes. CVT
      510 at doses of 0.3 to 10 microg/kg had no effect on sinus rate, HV interval, or
      systemic blood pressure, and was not associated with serious adverse effects. At
      doses of 15 and 30 microg/kg, CVT-510 produced transient second/third degree AV
      heart block in all four patients treated. One of these patients also had a
      prolonged sedative effect that was reversed with aminophylline. CONCLUSIONS: CVT
      510 promptly prolongs AV nodal conduction and does not affect sinus rate or blood
      pressure. Selective stimulation of the A(1)-adenosine receptor by CVT-510 may be
      useful for immediate control of heart rate in atrial fibrillation/flutter and to
      convert paroxysmal supraventricular tachycardia to sinus rhythm, while avoiding
      vasodilatation mediated by the A(2)-adenosine receptor, as well as the
      vasodepressor and negative inotropic effects associated with beta-adrenergic
      receptor blockade and/or calcium channel blockers.

PMID- 11584331
TI  - Female gender does not influence the magnitude of ibutilide-induced
      repolarization delay and incidence of torsades de pointes in an in vivo rabbit
      model of the acquired long QT syndrome.
AB  - BACKGROUND: Clinical and experimental in vitro observations indicate that female
      gender is associated with a higher risk of developing torsades de pointes with
      repolarizing-delaying agents. The present study addressed the question of gender
      difference in the susceptibility towards developing torsades de pointes in a
      rabbit model of the acquired long QT syndrome in vivo. METHODS AND RESULTS:
      Female (F, n = 40) or male (M, n = 40) NZW rabbits, characterized as young (Y, n
      = 20) or adult (A, n = 20) were anesthetized with alpha-chloralose and sensitized
      to developing torsades de pointes by a continuous infusion of methoxamine. The
      class III antiarrhythmic agent ibutilide was subsequently infused at a rate of 8
      nmol/kg/min for 30 minutes maximum. Before commencement of drug infusion, no
      gender-related differences in the QT interval were observed (121 +/- 1.9 msec and
      126 +/- 3.3 msec in FA and in MA and 116 +/- 1.6 msec and 113 +/- 1.7 msec in the
      FY and MY, respectively). Infusion of ibutilide was associated with a rapid and
      marked increase in the QT interval, which did not differ significantly between
      the groups. Hence, the maximal QT lengthening observed was 39 +/- 3.1% in FA, 46
      +/- 5.7% in MA, 38 +/- 3.9% in FY and 36 +/- 3.4% in MY, respectively (p > 0.05
      between gender). In the adults, the incidence of torsades de pointes in F was 70%
      and in M 90% (p = 0.235), whereas in the young, the incidence in F was 45% and in
      M 70% (p = 0.200). The cumulative doses of ibutilide causing torsades de pointes
      were not statistically significantly different between the four groups of rabbits
      (70 +/- 15.5 nmol/kg in FA, 50 +/- 5.3 nmol/kg in MA, 59 +/- 17.2 nmol/kg in FY
      and 61 +/- 15.9 nmol/kg in MY, respectively). CONCLUSIONS: In this in vivo rabbit
      model of the acquired long QT syndrome, female gender was not associated with a
      longer repolarization time (QT interval), an excessive change in the baseline QT
      interval or a higher incidence of torsades de pointes in response to ibutilide
      challenge.

PMID- 11584332
TI  - Pimozide (Orap) prolongs cardiac repolarization by blocking the rapid component
      of the delayed rectifier potassium current in native cardiac myocytes.
AB  - BACKGROUND: Several cases of QT prolongation and ventricular tachyarrhythmia have
      been reported with pimozide, a potent neuroleptic useful in the management of
      motor and phonic tics associated with Tourette syndrome. To further elucidate the
      mechanism underlying these clinical observations, the effects of pimozide on
      monophasic action potential duration (MAPD(90)) and on potassium currents
      involved in the repolarization of native isolated ventricular myocytes were
      examined. METHODS AND RESULTS: Studies were undertaken in eight isolated guinea
      pig hearts that demonstrated reverse rate-dependent prolongation of cardiac
      repolarization by pimozide 100 nmol/L. Action potential duration increased 24%
      from baseline 115 +/- 2 to 142 +/- 4 msec with pimozide 100 nmol/L during pacing
      at 250 msec cycle length, while a 10% increase from 97 +/- 2 to 107 +/- 3 msec
      was seen with pacing at a cycle length of 150 msec. Experiments in native
      isolated ventricular myocytes (n = 20) demonstrated concentration-dependent block
      of the rapid component (I(Kr)) of the delayed rectifier potassium current: tail
      current was decreased by 50% at 15 nmol/L. CONCLUSIONS: Pimozide possesses
      cardiac electrophysiological effects similar to those of class III antiarrhythmic
      drugs. These effects are concentration-dependent and observed at recommended
      dosages of the drug. Since pimozide is strongly metabolized by CYP3A4, special
      care should be taken to avoid potential pharmacokinetic interactions leading to
      high plasma levels of pimozide and proarrhythmia.

PMID- 11584333
TI  - Effects of tedisamil on cardiovascular tissues isolated from normo- and
      hypertensive rats.
AB  - BACKGROUND: This study was undertaken to characterize the effects of tedisamil on
      isolated rat cardiovascular tissues, and identify actions that could be
      beneficial or detrimental in the treatment of cardiac disease. RESULTS: Tedisamil
      prolonged the Wistar Kyoto normotensive rat (WKY) left ventricular action
      potential and augmented the force of contraction of left ventricle strips. On the
      12-month-old SHR model of cardiac hypertrophy, the augmenting effects of
      tedisamil at 10(-6) and 3 x 10(-6) M were reduced. On the 21-month-old SHR model
      of heart failure, the augmenting effects of tedisamil at 10(-6) and 3 x 10(-6) M
      were further reduced. The augmenting effect of tedisamil at 10(-5) M was reduced
      to 47%. The rate of the right atrium of 16- to 17-month-old WKY was reduced by
      tedisamil at 10(-5) and 10(-4) M, and tedisamil had a similar effect on the SHR
      right atrium. Tedisamil at 10(-6)--3 x 10(-5) M contracted the portal veins of
      WKY and aortae of 12-month-old WKY and SHR. CONCLUSIONS: The positive inotropic
      and negative chronotropic effects of tedisamil in the rat, which are partially or
      fully maintained in hypertrophied or failing myocardium would be beneficial in
      the treatment of heart failure. In contrast, the vasoconstrictor action of
      tedisamil will be detrimental in heart failure.

PMID- 11584334
TI  - Reactive oxygen species and endotoxic shock: effect of dimethylthiourea.
AB  - The effects of endotoxemia on the cardiac function and contractility, oxygen
      radical production by polymorphonuclear leukocytes (PMNL-CL), cardiac antioxidant
      reserve (LV-CL), antioxidant enzymes (superoxide dismutase [SOD], catalase,
      glutathione peroxidase [GSH-P(X)]) and malondialdehyde (MDA); and plasma creatine
      kinase (CK) and lactate in the absence or presence of dimethylthiourea (DMTU), an
      antioxidant, in anesthetized dogs were studied. Dogs were assigned to three
      groups: group 1, control; group II, endotoxin (ET) (5 mg/kg body wt
      intravenously), and group III, ET + DMTU (500 mg/kg intravenously). ET produced
      decreases in the cardiac function and contractility, antioxidant reserve,
      antioxidant enzymes; and increases in PMNL-CL, cardiac MDA, plasma CK, and
      lactate. Pretreatment with DMTU attenuated the ET-induced cardiac dysfunction and
      changes in the cardiac MDA, antioxidant reserve, and antioxidant enzymes, PMNL
      CL, and plasma CK and lactate levels. These results suggest that reactive oxygen
      species may be involved in the deterioration of cardiac function and
      contractility, and cellular injury during endotoxic shock and that antioxidants
      may be of value in the treatment of endotoxic shock.

PMID- 11584335
TI  - Vasodilator responses to ATP and UTP are cAMP dependent in the mesenteric
      vascular bed of the cat.
AB  - BACKGROUND: This study was designed to examine the responses to and the mechanism
      by which purinergic agonists decrease vascular resistance in the mesenteric
      vascular bed of the cat. METHODS AND RESULTS: Injections of ATP, UTP, and 2
      MethylThioATP (2-MetSATP) into the mesenteric perfusion circuit elicited dose
      dependent decreases in perfusion pressure while injections of beta,gamma
      MethylATP (beta,gamma-MetATP) produced a biphasic response with an initial
      vasopressor response followed by a vasodilator response. The order of potency of
      the vasodilator response was 2-MetSATP > ATP > UTP > beta,gamma-MetATP. The
      vasodilator responses to ATP, UTP, 2-MetSATP, and beta,gamma-MetATP were
      increased in duration by the cAMP phosphodiesterase inhibitor, rolipram. However,
      vasodilator responses were not altered by the adminstration of a nitric oxide
      synthase inhibitor, a cGMP phosphodiesterase inhibitor, or a cyclooxygenase
      inhibitor. Treatment with PPADS, a P2X(1), P2Y(1), and P2Y(4) receptor
      antagonist, did not alter vasodilator responses to the purinergic agonists;
      however, the vasopressor component of the response to beta,gamma-MetATP was
      decreased. CONCLUSIONS: These data suggest that ATP, UTP, 2-MetSATP, and
      beta,gamma-MetATP dilate the mesentary vascular bed in the cat by a cAMP
      dependent mechanism, and that nitric oxide or prostaglandin release, cGMP
      accumulation, or activation of P2X(1), P2Y(1), or P2Y(4) receptors play little or
      no role in mediating vasodilator responses to the purinergic agonists in this
      regional vascular bed. In addition, these results suggest that the pressor
      component of the response to beta,gamma-MetATP is mediated by the activation of
      P2X(1) receptors.

PMID- 11584336
TI  - Electrophysiologic and antiarrhythmic effects of the new class III antiarrhythmic
      drug KCB-328 in experimental canine atrial flutter.
AB  - BACKGROUND: The electrophysiologic and antiarrhythmic effects of a new class III
      antiarrhythmic drug (KCB-328), a delayed rectifier potassium current (IKr)
      blocker with minimal reverse use-dependent effect on atrial repolarization, were
      evaluated in the canine night atrial crush-injury model of atrial flutter (AFL).
      METHODS: Ten anesthetized, open-chest dogs, were studied after right atrial crush
      injury. Atrial effective refractory period (ERP), conduction velocity (CV),
      wavelength, and dispersion of refractoriness were determined during programmed
      stimulation (S1S2 at S1S1 = 200, 300, 400, and 500 msec) at four sites via a
      mapping plaque sutured on the right atrial free wall. Right and left ventricular
      ERP were similarly measured at single sites. Electrophysiological parameters were
      determined at baseline and following sequential cumulative doses of KCB-328 (10,
      30, 100, and 300 microg/kg). RESULTS: Sustained AFL was inducible in 7/10 dogs by
      rapid pacing following baseline electrophysiologic measurements. KCB-328
      significantly prolonged sinus cycle length, but had no effect on PR interval, and
      prolonged QTc only at the highest dose level. KCB-328 significantly prolonged
      atrial ERP and wavelength and ventricular ERP, and significantly reduced
      dispersion of atrial refractoriness. KCB-328 significantly prolonged AFL cycle
      length, and increasing doses progressively terminated sustained AFL and prevented
      its reinduction by pacing. No adverse hemodynamic or ventricular proarrhythmic
      effects were observed. CONCLUSIONS: The electrophysiologic profile of KCB-328 in
      this canine model of AFL, particularly its lack of reverse use-dependent effect
      on atrial refractoriness, suggests that it may have significant antiarrhythmic
      potential in treatment of atrial arrhythmias.

PMID- 11584337
TI  - HRCT findings of amiodarone pulmonary toxicity: clinical and radiologic
      regression.
AB  - Amiodarone is an antiarrhythmic drug that can cause interstitial pneumonitis
      leading to pulmonary fibrosis. A 62-year-old man suffering from atrial
      fibrillation and recurrent dyspnea was treated with amiodarone. After 15 months
      of treatment, HRCT revealed bilateral interstitial and alveolar opacifications
      with high-attenuating pleural-parenchymal consolidations, suggesting amiodarone
      induced pneumonitis. Three months after cessation of amiodarone treatment, HRCT
      shows complete regression of pneumonitis. Amiodarone pneumonitis can be
      misinterpreted and mistreated in patients with further underlying diseases. The
      present case report demonstrates the diagnostic value of HRCT in the diagnosis of
      interstitial pneumonitis.

PMID- 11584338
TI  - Variable supplemental oxygen during recovery does not reduce retinal neovascular
      severity in experimental ROP.
AB  - PURPOSE: To test the hypothesis that variable supplemental oxygen (VSO) during
      recovery is not as effective as constant supplemental oxygen treatment at
      reducing retinal neovascular severity in the newborn rat model of retinopathy of
      prematurity (ROP). METHODS: The ROP model consists of raising newborn rats in
      variable oxygen for 14 days and then allowing them to recover during the next 6
      days (until day 20). During this recovery period, two VSO protocols were
      examined: 1) 24 hr cycled (28% for 24 hr and 21% for 24 hr) as a control, and 2)
      interrupted (28% for 23.75 hr and 21% for 0.25 hr). On day 20, retinas from both
      eyes of each animal were dissected, stained with ADPase, and analyzed for
      neovascular (NV) incidence, severity, and peripheral avascularity. RESULTS: No
      significant differences (P > 0.05) in NV incidence and severity were found
      between the 24 hr cycled (control) (95% (38/40), median 5 clockhrs, range 0.5-9,
      n = 38) and interrupted VSO groups (89% (40/45), 3.5 clockhrs, 0.5-10.5, n = 40).
      However, retinal NV severity from both VSO groups were significantly greater (P <
      0.05) than that previously reported for constant supplemental oxygen treatment.
      Percent peripheral avascularities were not significantly different (P > 0.05)
      between the two VSO groups. CONCLUSIONS: These results support our hypothesis
      since both VSO conditions were significantly less effective at reducing retinal
      NV than constant supplemental oxygen during recovery. The possible application of
      these results to STOP-ROP trial is discussed.

PMID- 11584339
TI  - Proximal arterial vasoconstriction precedes regression of the hyaloid
      vasculature.
AB  - PURPOSE: To determine whether constriction of proximal arterial vessels precedes
      involution of the distal hyaloid vasculature in the mouse, under normal
      conditions, and whether this vasoconstriction is less pronounced when the distal
      hyaloid network persists, as it does in oxygen-induced retinopathy (OIR).
      METHODS: Photomicrographs of the vasa hyaloidea propria were analysed from pre
      term pups (1-2 days prior to birth), and on Days 1-11 post-birth. The OIR model
      involved exposing pups to approximately 90% O(2) from D1-5, followed by return to
      ambient air. At sampling times pups were anaesthetised and perfused with india
      ink. Retinal flatmounts were also incubated with FITC-lectin (BS-1, G.
      simplicifolia,); this labels all vessels, allowing identification of vessels not
      patent to the perfusate. RESULTS: Mean diameter of proximal hyaloid vessels in
      pre-term pups was 25.44 +/- 1.98 microm; +/- 1 SEM). Within 3-12 hrs of birth,
      significant vasoconstriction was evident (diameter:12.45 +/- 0.88 microm), and
      normal hyaloid regression subsequently occurred. Similar vasoconstriction
      occurred in the O(2)-treated group, but this was reversed upon return to room
      air, with significant dilation of proximal vessels by D7 (diameter: 31.75 +/-
      11.99 microm) and distal hyaloid vessels subsequently became enlarged and
      tortuous. CONCLUSIONS: Under normal conditions, vasoconstriction of proximal
      hyaloid vessels occurs at birth, preceding attenuation of distal hyaloid vessels.
      Vasoconstriction also occurs in O(2)-treated pups during treatment, but upon
      return to room air, the remaining hyaloid vessels dilate proximally, and the
      distal vessels become dilated and tortuous. These observations support the
      contention that regression of the hyaloid network is dependent, in the first
      instance, on proximal arterial vasoconstriction.

PMID- 11584340
TI  - Measurement of iris color using computerized image analysis.
AB  - PURPOSE: To develop a standardized method for measuring from iris photographs,
      light and dark segments of areas and densities of iris color. METHODS:
      Computerized image analysis was used to measure the iris photographs. The
      reproducibility of this method was studied in 30 normal eyes with three different
      colored irides, green-brown, blue-grey brown and yellow-brown. Three photographs
      were taken of each iris with a slit lamp camera at three different exposures at
      baseline. The photographs were repeated with exposure providing for the best
      reproducibility at 6.5 +/- 1.7 months as a first follow-up after baseline and 3.6
      +/- 0.8 months following the first follow-up visit. At least one measurement was
      made for each photograph. RESULTS: The mean percent coefficient of variation
      (standard deviation of triplicate measurements/mean x 100) ranged from 1.0 to
      4.1% for area and density measurements. Furthermore, the range of mean percent
      differences between baseline and follow-up visits ranged from 1.2 to 6.3%.
      CONCLUSION: We have developed a standardized method which appears suitable for
      measuring changes over time in iris color.

PMID- 11584341
TI  - Video-assessment of tear meniscus height in elderly Caucasians and its
      relationship to the exposed ocular surface.
AB  - PURPOSE: An adequate volume of tears is considered essential to prevent
      desiccation of the exposed ocular surface, especially in elderly individuals. Few
      assessments of tear meniscus height (TMH) have however been reported for elderly
      individuals. METHODS: Close-up images of the lower marginal tear strip were
      obtained by videography over about 30 s in 56 elderly individuals (38 women, 18
      men; 71 +/- 5 years of age) without significant eye disease and having a
      functional lacrimal system (Schirmer test). From such an "en face" view, the
      vertical height of the tear meniscus (TMH) at the lower eyelid was measured from
      stopped video frames. Firstly, TMH was assessed at the mid-point of the eyelid
      from five frames separated by 5 s; these values were averaged to give a time
      averaged assessment of TMH (a tTMH value). Secondly, a position-averaged method
      (pTMH) was used in which TMH was assessed at 5 locations along the eyelid margin
      from a single frame that included several mm of marginal tear strip, and an
      average value calculated. The videographs were also used to assess palpebral
      aperture and the exposed ocular surface, a 1 min Schirmer test measure (closed
      eye) was also made, and keratometry data was available for most subjects.
      RESULTS: A wide range of average values was encountered for both tTMH (range
      0.057 to 0.271 mm) and pTMH (0.031 mm to 0.325 mm). The group-averaged tTMH value
      was 0.172 +/- 0.047 mm (median 0.164 mm) while the group-averaged pTMH value was
      0.171 +/- 0.058 mm (median 0.168 mm), with no difference being found between the
      two methods (p = 0.84, paired t-test). With either method, the apparent TMH value
      was greater when the exposed ocular surface value (average 1.68 +/- 0.51 cm(2))
      was lower and vice versa, and was statistically-significant for the tTMH measures
      (p = 0.02, r = 0.32), but not the pTMH measures (p = 0.18, r = 0.18). Neither TMH
      measure was related to the Schirmer test values or to central corneal curvature.
      CONCLUSIONS: The results indicate that healthy elderly individuals can be
      expected to have a measurable lower marginal tear strip, and that objective
      assessment of this may be a useful alternative to the Schirmer test. A possible
      association was found between the measures of TMH and the palpebral aperture
      height (and thus the exposed ocular surface), and so might need to be considered
      when TMH is assessed.

PMID- 11584342
TI  - Flufenamic acid enhances current through maxi-K channels in the trabecular
      meshwork of the eye.
AB  - PURPOSE: Flufenamic acid relaxes trabecular meshwork, a smooth muscle-like tissue
      involved in the regulation of ocular outflow in the eye. In this study, we
      attempted to determine if ionic channels are involved in this response. METHODS:
      Cultured human (HTM) and bovine (BTM) trabecular meshwork cells were investigated
      using the patch-clamp technique. RESULTS: In trabecular meshwork, flufenamic acid
      (10(-5) M) reversibly stimulated outward current to 406 +/- 71% of initial
      outward current level in BTM (n = 10) and 294 +/- 75% of initial current level in
      HTM (n = 12) in all cells investigated; no significant differences emerged. The
      response was dosage-dependent. Replacement of potassium in all solutions
      eliminated the response to flufenamic acid (n = 4, BTM). Blocking K(ATP )
      channels with glibenclamide (10(-5) M, n = 6) and small-conductance calcium
      activated potassium channels with apamin (10(-6) M, n = 5) had no effect. A
      direct effect on calcium channels could also not be detected. Blockage of the
      large-conductance calcium-activated potassium channel (maxi-K) by iberiotoxin
      (10(-7) M) suppressed 87 +/- 9% (n = 6; HTM) and 91 +/- 10% (n = 6; BTM) of the
      response. Depleting the cells of calcium did not significantly alter the response
      to flufenamic acid. CONCLUSIONS: Flufenamic acid stimulates maxi-K channels in
      trabecular meshwork of both human and bovine origin. This should lead to
      hyperpolarization, closure of L-type channels and lowered cytosolic calcium
      levels, possibly explaining the relaxation observed in response to this
      substance.

PMID- 11584343
TI  - NMR relaxation studies of syneretic response to pressure change in bovine lenses.
AB  - PURPOSE: Reversible syneretic response to pressure in bovine and rhesus monkey
      lenses has been demonstrated previously by invasive techniques, such as
      differential scanning calorimetry and thermogravimetric analysis. This study is
      designed to investigate whether such a response could be observed by non-invasive
      techniques, namely by relaxographic imaging studies, in situ, in the intact,
      albeit excised lens. METHODS: Excised bovine lenses were incubated in media at 37
      degrees C in specialized pressure chambers for 24 hrs. Three pressures, 2, 1 and
      0.03 atm, were employed. The pressure chambers were placed in the cavity of an
      NMR magnet. Seven sections of the lens, under 2 atm pressure, from anterior outer
      cortex to posterior outer cortex were imaged and the T(1) (spin-lattice) and T(2
      ) (spin-spin) relaxation data on each section were collected. The pressure was
      then released and NMR data were collected under 1 atm. Similar arrangement was
      followed on lenses under initial 0.03 atm pressure. T(1) and T(2) relaxations
      were analyzed by fitting pixel intensity to one and two term exponential
      expressions. RESULTS: Analysis of the time dependence of the T(2) relaxation time
      indicated that the response to a change in pressure is complete within 2 hours.
      Both T(1) and T(2) relaxation times showed minimal values in the nuclear region
      and maxima at the two outer cortexes. With increasing pressure both relaxation
      times decrease. The effect of pressure on both relaxation times was smaller in
      the nucleus and more enhanced at the outer cortexes. The pre-exponential terms of
      the fittings of both T(1) and T( 2) relaxations indicate the amount of protons
      participating in the relaxation. Thus they serve as a population index. The T(2)
      population index had a maximum in the nucleus and minima in the two cortexes. The
      population index of T(1) relaxation exhibited minimal value in the nucleus and
      maxima at the two cortexes. The pre-exponential term of T(2) relaxation increased
      with increasing pressure. The pre-exponential term of T(1) relaxation did not
      show consistent pressure dependence. CONCLUSIONS: The positional dependence of
      T(2) relaxation times as well as that of its population index indicated that it
      represents the behavior of the bound water in the lens. The positional dependence
      of T(1) population index suggests that this relaxation represents the total water
      that has a minimal value in the nucleus. Both the relaxation times as well as the
      population indices indicated that as pressure increases the strength of hydrogen
      bonding as well as the amount of bound water increases. This also means that the
      free water/bound water ratio decreases with increasing pressure. Thus NMR imaging
      and relaxation studies confirm significant syneretic response to applied
      hydrostatic pressure in bovine lenses.

PMID- 11584344
TI  - Expression of plasma membrane Ca(2+)-ATPase in lenses from normal and hereditary
      cataract UPL rats.
AB  - PURPOSE: The regulation of calcium concentration in lens cells is important in
      the mechanisms of cataractogenesis. The Ca( 2+) level in cells is controlled by
      plasma membrane Ca(2+)-ATPase (PMCA). PMCA has several isoforms that are
      distributed in various cell types in the body. In this study, we investigated the
      PMCA mRNA expression in normal lenses and in lenses from rats with newly
      developed hereditary cataracts. METHODS: The rats used were the UPL strain of
      Sprague-Dawley rats, with (UPL) and without (normal) the dominant gene for
      cataracts. PMCA mRNA expression in the lens, brain, liver and kidney in the
      normal and UPL rats was detected by reverse transcription-PCR using isoform
      specific primers. Partial cDNA sequences of the lens PMCA were also determined.
      RESULTS: PMCA1, 2, 3 and 4 were expressed in the brain and kidney. Distinct from
      the brain, liver and kidney, only one isoform of PMCA, PMCA1b, was expressed in
      both normal and UPL rat lenses. Sequences of PMCA in normal and UPL rat lenses
      were not different. CONCLUSIONS: The present study demonstrated that PMCA1b is
      the only form of PMCA present in both normal and UPL rat lenses.

PMID- 11584345
TI  - Lysostaphin is effective in treating methicillin-resistant Staphylococcus aureus
      endophthalmitis in the rabbit.
AB  - PURPOSE: To determine the effectiveness of lysostaphin treatment of experimental
      endophthalmitis caused by methicillin-resistant Staphylococcus aureus (MRSA).
      METHODS: In one experiment, rabbits were injected in the mid-vitreous with 50 or
      200 CFU of S. aureus; untreated groups and groups injected intra-vitreally at 8
      or 24 hours postinfection with vehicle or lysostaphin (0.1 mg/ml) were compared
      in terms of CFU/ml vitreous at 24 or 48 hours postinfection. Histopathology of
      untreated and treated eyes was also compared. To quantify the potency of
      lysostaphin, additional rabbits were injected with 50 CFU of S. aureus and
      untreated eyes and eyes treated at 8 hours with 0.001, 0.01 or 0.05 mg/ml were
      compared in terms of CFU/ml vitreous at 24 hours postinfection. RESULTS: Vitreous
      of untreated eyes or vehicle-treated eyes injected with 50 or 200 CFU of S.
      aureus contained 5-10 million CFU/ml at 24 or 48 hours postinfection. All eyes
      treated with lysostaphin at 8 hours postinfection had less than 1 log CFU/ml in
      the vitreous (P >or= 0.0001). Similarly, eyes treated with lysostaphin at 24
      hours postinfection had approximately 1 log of CFU/ml at 48 hours postinfection.
      None of the untreated eyes were sterile and 88% or 50% of the eyes treated at 8
      or 24 hours postinfection, respectively, were sterile. Eyes treated with
      lysostaphin at 8, but not 24, hours postinfection had less pronounced pathologic
      changes than the untreated eyes (P = 0.002). A significant reduction in the
      CFU/ml vitreous at 24 hours postinfection was obtained by treating infected eyes
      at 8 hours postinfection with lysostaphin at concentrations of >or=0.001 mg/ml (P
      <or= 0.0034). CONCLUSIONS: Lysostaphin is effective in treating experimental
      endophthalmitis mediated by MRSA.

PMID- 11584346
TI  - Proteolysis by m-calpain enhances in vitro light scattering by crystallins from
      human and bovine lenses.
AB  - PURPOSE: To determine if proteolysis by the calcium-activated protease m-calpain
      (EC 34.22.17) enhances in vitro light scattering in crystallins from human and
      bovine lenses. METHODS: Total soluble proteins from bovine, human, and rodent
      lenses, betaH crystallin, or recombinant betaB1 polypeptide were pre-incubated in
      the presence or absence of activated m-calpain. Heat-induced light scattering was
      assayed by measuring changes in optical density at 405 nm. Proteolysis and
      cleavage sites were detected by SDS-PAGE, two dimensional electrophoresis, and N
      terminal Edman sequencing. RESULTS: The in vitro cleavage sites produced by m
      calpain on the N-termini of human betaB1, betaA3, and betaB2-crystallins were
      similar to some of those on bovine and rat crystallins. Proteolysis of alpha- and
      beta-crystallins was associated with enhanced, heat-induced light scattering by
      human and bovine lens proteins. CONCLUSIONS: Proteolysis may be a contributing
      factor in the insolubilization of crystallins occurring during normal maturation
      of lens or during cataract formation in such species as man and cows.

PMID- 11584347
TI  - Reduction of intraocular pressure by topical administration of an inhibitor of
      the Rho-associated protein kinase.
AB  - PURPOSE: Rho-associated coiled coil-forming protein kinase (ROCK) is a downstream
      target of a small GTPase, Rho. The kinase has been reported to regulate
      actomyosin-based contractility of smooth muscles by modulation of myosin
      phosphatase activity. Contractility of ciliary muscle could be implicated in
      regulation of intraocular pressure while that of ocular vessels could affect
      blood flow to retina. The present study has been performed to investigate the
      effect of a ROCK inhibitor on intraocular pressure in rabbits. METHODS: An
      inhibitor of ROCK, Y-27632, was dissolved in an ophthalmic solution and topically
      administered to the eye of a Japanese white rabbit. Intraocular pressure was
      measured by pneumatonography (n = 12, 24 eyes). Constriction of ciliary muscle
      was measured by the Magnus method using 12 eyes. RESULTS: Topical application of
      0.1 and 0.03% Y-27632 significantly decreased the intraocular pressure, with
      maximum decreases of 5.3 and 4.3 mm Hg after 90 minutes compared with the control
      eye. Y-27632 inhibited the carbachol-induced constriction of rabbit ciliary
      muscle. CONCLUSIONS: The ROCK inhibitor reduced intraocular pressure in rabbits
      by topical instillation. The inhibitor relaxed the excised ciliary muscle which
      was previously constricted by carbachol suggesting that the inhibitor acts to
      increase the uveoscleral outflow. Our results suggest that the ROCK inhibitor is
      a promising treatment for glaucoma therapy in the next generation.

PMID- 11584348
TI  - It is past due.

PMID- 11584349
TI  - Prescribing practices of advanced practice psychiatric nurses: Part I-
      Demographic, educational, and practice characteristics.
AB  - This study was designed to identify and describe the prescribing practices of
      advanced practice psychiatric nurses. Part I describes the demographic,
      educational, and clinical setting characteristics. A survey method was used with
      N = 88 nurses representing seven different states. Nurse prescribers were:
      younger than nonprescribers, employed in community mental health settings, and
      voluntarily using a consulting physician arrangement. Limitations on practice
      included: statute formulary, controlled substances, and formulary/protocols with
      a consulting physician. Results suggest nurses' prescribing practices are used in
      outpatient settings, viewed as conservative, with a value on physician
      collaboration even in the absence of legal mandates.

PMID- 11584350
TI  - Community nursing support for clients with schizophrenia.
AB  - A true experimental, posttest only, control group design was used to pilot test
      the effectiveness of a telephone nursing intervention in increasing community
      survival, and decreasing the number and length of rehospitalizations for persons
      with schizophrenia. The vulnerability model was used as a framework for the
      study. The intervention was hypothesized to function as a moderating factor to
      reduce the effects of stress on vulnerable persons with schizophrenia.
      Experimental subjects received telephone nursing intervention weekly for 3
      months; control subjects received informational calls at weeks 6 and 12.
      Readmission rates were 13% (n = 2) for experimental subjects and 23% (n = 5) for
      controls. Compared with controls, experimental subjects experienced a 4% increase
      in community survival and a 27% reduction in length of stay if readmission
      occurred. These preliminary data suggest that telephone intervention can increase
      community survival in persons with schizophrenia. Future studies should focus on
      increasing sample size and refining the intervention.

PMID- 11584351
TI  - Seeking and obtaining mental health services: what do parents expect?
AB  - This study examined parents' expectations about seeking and obtaining mental
      health care. Using the Expectations of Mental Health Care survey, structured
      interviews were conducted with 235 parents with children between the ages of 5
      and 19; most were African American. Expectations were assessed in four areas:
      treatment effectiveness, provider/client relationship, accessibility of mental
      health services, and social and cultural factors, e.g., stigma. Parents reported
      a number of negative expectations, and black parents had significantly more
      negative expectations than white parents. The findings suggest that attitudes and
      expectations may influence parents' decision to seek mental health care for their
      child.

PMID- 11584352
TI  - A comparison of life satisfaction and mood in nursing home residents and
      community-dwelling elders.
AB  - This study compared life satisfaction and mood in a sample of 138 cognitively
      intact and ambulatory elders, including 70 who lived in nursing homes and 68 who
      lived independently in the community. Community-dwelling elders reported greater
      life satisfaction, and scored higher on the Vigor-Activity subscale of the
      Profile of Mood States (POMS) than those who lived in a nursing home. Nursing
      home residents scored higher on the Depression-Dejection, Tension-Anxiety, and
      Confusion-Bewilderment subscales of the POMS. No between group differences were
      shown on the Anger-Hostility and Fatigue-Inertia subscales of the POMS. The
      diminished life satisfaction and high depression found in the nursing home
      residents hold immediate implications for professionals who work in this area.

PMID- 11584353
TI  - Is it legal to be crazy: an ethical dilemma.
AB  - The legal versus ethical rights of behavioral health patients have long
      complicated inpatient treatment plans and challenged the creative thinking skills
      of behavioral health nurses. This article examines the practical ethics of
      involuntary treatment with focus on the principles of respect, individual
      autonomy, and the right for self-determination. Through an examination of an
      actual case in Florida, this discussion highlights the ethical dilemma of
      treating an involuntary patient versus releasing a potentially dangerous
      individual back into society. Practical solutions to this ethical dilemma are
      offered.

PMID- 11584355
TI  - Hepatitis B e antigen-negative chronic hepatitis B.

PMID- 11584356
TI  - Primary sclerosing cholangitis is associated to an extended B8-DR3 haplotype
      including particular MICA and MICB alleles.
AB  - Susceptibility to primary sclerosing cholangitis (PSC) is associated with HLA-B8,
      -DR3, -DR2, and -DR6. It is not established whether these HLA genes or closely
      linked genes confer the primary disease susceptibility. MICA and MICB genes are
      found in the class I region between HLA-B and DRB. MICA is expressed in
      gastrointestinal epithelium and activates gammadelta T cells in the gut. Because
      PSC is strongly associated with inflammatory bowel disease, we investigated
      whether MICA and MICB contribute to the HLA-associated genetic susceptibility to
      develop PSC. The study included 130 PSC patients and 306 healthy controls,
      previously typed for HLA class I and II genes, typed for 5 MICA and 15 MICB
      microsatellite alleles. The phenotype frequencies of MICA5.1 and MICB24 were
      significantly increased among PSC patients compared with controls (90% vs. 74%;
      odds ratio [OR] = 3.2; P(c) = 3 x 10(-3) and 58% vs. 29%; OR = 3.3; P(c) < 1 x
      10(-7), respectively). When stratified for B8- or DR3-positive and -negative
      individuals, the association of these markers to PSC was no longer evident.
      However, we observed that B8 and DR3 were associated to PSC only in the presence
      of both MICA5.1 and MICB24 markers. The frequency of individuals carrying all 4
      alleles was significantly increased among the PSC patients compared with controls
      (49% vs. 18%; OR = 4.5; P(c) < 1 x 10(-7)). Our data indicate that PSC is
      associated to the extended B8-MICA5.1-MICB24-DR3 haplotype.

PMID- 11584357
TI  - Immunoglobulin gene usage and immunohistochemical characteristics of human
      monoclonal antibodies to the mitochondrial autoantigens of primary biliary
      cirrhosis induced in the XenoMouse.
AB  - The immunodominant antimitochondrial antibody (AMA) response in primary biliary
      cirrhosis (PBC) is directed against the E2 component of pyruvate dehydrogenase
      (PDC-E2). The nature of the clonal selection process is unclear, and to address
      this issue, we took advantage of a transgenic technology, XenoMouse, that
      contains 80% of the human immunoglobulin (Ig) variable gene repertoire and can
      produce high-affinity human antibodies to virtually any immunogen without
      evidence of clonal bias. We immunized mice with PDC-E2 to obtain 13 HmAbs,
      including 4 IgG(2) and 9 IgM isotypes. Immunoglobulin gene analysis was unique
      and demonstrated a clonal bias; the immunoglobulin gene usage was considerably
      different from other antibody responses analyzed in XenoMouse systems. Four of
      the 13 mAbs recognized the inner lipoyl domain of PDC-E2, 2 of 13 recognized the
      entire PDC-E2 molecule, 4 of 13 recognized PDC-E2 and OGDC-E2, 1 of 13 recognized
      OGDC only, 1 recognized BCOADC-E2 only, and 1 recognized an unidentified 100-kd
      mitochondrial protein. Immunohistochemical staining using these HmAbs produced
      mitochondrial staining of septal bile ducts in both PBC and control livers. Ig
      gene analysis showed that 7 of 13 HmAbs used the V(H)3 and 4 of 13 used VH4 gene
      repertoire, respectively. Three of 7 V(H)3 antibodies used the same Ig VH3-21
      gene family found in human AMA from patients with PBC. The CDRs of these
      autoantibodies were slightly mutated when compared with the sequences present
      within the Ig germline genes. In conclusion, the XenoMouse not only recapitulates
      the unique specificity and restriction of PBC patients, but indicates that the
      autoantibodies are derived from a restricted clonal selection process. Such data
      suggest that the original immunogen leads to somatic mutation without subsequent
      development of determinant spreading.

PMID- 11584358
TI  - Differential expression of cyclooxygenase-2 (COX-2) in human bile duct epithelial
      cells and bile duct neoplasm.
AB  - It is well known that chronic inflammatory conditions involving the bile ducts
      predispose to the development of bile duct carcinoma, although the relationship
      between chronic inflammation and malignant transformation is unclear. In this
      study, by combining immunohistochemistry and computer imaging techniques, we
      quantified and compared the cyclooxygenase-2 (COX-2) protein expression levels of
      epithelial cells according with their histopathological backgrounds. This
      technique revealed that the highest levels of COX-2 were expressed in bile duct
      carcinoma cells, mainly in cytoplasm, and the expression pattern was homogenous
      and abundant. Moderate levels of COX-2 protein expression were also observed in
      noncancerous epithelial cells with inflammatory reaction, but the staining
      intensity was heterogeneous among the positive cells exhibiting inflammation. In
      contrast, only scattered weak reactivity of COX-2 protein was observed in the
      noncancerous bile duct epithelial cells without inflammatory reaction. Moreover,
      bile duct epithelial cells in primary sclerosing cholangitis (PSC) showed very
      strong expression of COX-2 protein, that was comparable with carcinoma cells. On
      the other hand, primary biliary cirrhosis (PBC) epithelial cells showed moderate
      levels of COX-2 expression. In addition, specific COX-2 inhibitors, JTE-522 and
      NS-398, directly inhibited the growth of 4 bile duct carcinoma and 1 gall bladder
      carcinoma cell lines that expressed COX-2 protein, in vitro. These data suggest
      that COX-2 expression might regulate carcinogenesis of bile duct epithelial cells
      in inflammatory regions and tumor progression in this cancer. The data also
      suggest that COX-2 selective inhibitors might have therapeutic effects not only
      on bile duct carcinoma, but other hepatobiliary carcinomas.

PMID- 11584359
TI  - Intraductal papillary neoplasia of the liver associated with hepatolithiasis.
AB  - Intraductal papillary growth of neoplastic biliary epithelia with a fine
      fibrovascular stalk (intraductal papillary neoplasia of liver [IPN-L]) resembling
      intraductal papillary mucinous neoplasm of pancreas is occasionally associated
      with hepatolithiasis. In this study, 136 cases of hepatolithiasis in Taiwan,
      between January 1998 and March 2000, and an additional 21 cases of IPN-L before
      December 1998, were examined histologically. IPN-L was found in 41 of 136
      hepatolithiasis cases (30.1%). Sixty-two IPN-L cases (42 women and 20 men; age
      range, 59.8 +/- 10 years) were divided into 4 types (type 1, IPN-L with low-grade
      dysplasia, 23 cases; type 2, IPN-L with high grade dysplasia, 11 cases; type 3,
      IPN-L with in situ and microinvasive carcinoma, 13 cases; and type 4, IPN-L of
      types 2 and 3 with distinct invasive carcinoma, 15 cases). Intraductal spreading
      and glandular involvement were commonly observed in all types. About half of
      types 3 and 4 cases had mucobilia, and mucinous carcinoma was variably found in
      two thirds of group 4 patients. IPN-L frequently showed variable gastroenteric
      differentiation such as goblet cells and foveolar and colon-like metaplasia. IPN
      L with goblet cells and colon-like metaplasia was frequently associated with
      overproduction of mucin and mucobilia (P <.01). In Japan, IPN-L was not frequent
      in hepatolithiasis (12 of 135 cases). In conclusion, IPN-L forms a spectrum of
      biliary neoplasm in hepatolithiasis. It often displays variable gastroenteric
      metaplasia and significant intraductal spread. IPN-L tends to progress to
      mucinous carcinoma. Formerly reported "mucin-producing intrahepatic
      cholangiocarcinoma" with a favorable prognosis is included in IPN-L.

PMID- 11584360
TI  - Autoimmune hepatitis with incidental histologic features of bile duct injury.
AB  - Bile duct changes are atypical of autoimmune hepatitis. Our aims were to assess
      the frequency and significance of these changes in classical disease. Liver
      biopsy specimens were reviewed under code from 84 patients who satisfied
      international scoring criteria for autoimmune hepatitis, and the findings were
      correlated with clinical features and outcome. Twenty patients (24%) had biliary
      changes, including 6 with destructive cholangitis, 4 with ductopenia, and 10 with
      nondestructive cholangitis. Patients with and without bile duct changes had
      similar laboratory findings. Diagnostic scores for autoimmune hepatitis were
      lower in patients with bile duct changes (16.6 +/- 0.6 vs. 19.1 +/- 0.2, P
      <.0001). The frequencies of scores sufficient for a definite (80% vs. 97%, P
      =.03) or probable diagnosis (20% vs. 3%, P =.03) were also less in this group.
      Patients with destructive cholangitis and/or ductopenia responded as well to
      therapy as patients with nondestructive cholangitis, and outcomes in each group
      were similar to those of patients without biliary changes. We concluded that
      biliary changes can occur in classic autoimmune hepatitis, and they are not
      associated with distinctive clinical features or treatment response. They may be
      coincidental findings associated with classic disease or weak expressions of a
      variant syndrome. In the absence of a cholestatic clinical syndrome, they do not
      compel a different management strategy.

PMID- 11584361
TI  - Hereditary thrombophilia as a cause of Budd-Chiari syndrome: a study from Western
      India.
AB  - The inherited deficiencies of protein C, protein S, antithrombin III, factor V
      Leiden mutation, prothrombin gene polymorphism, and antiphospholipids were
      studied in 53 Budd-Chiari syndrome (BCS) and 33 portal vein thrombosis (PVT)
      cases and compared with 223 age- and sex-matched controls. Protein C deficiency
      was detected in 7 (13.2%), protein S in 3 (5.7%), and antithrombin III in 2
      (3.8%) of the BCS cases. Factor V Leiden was the most common risk factor, i.e.,
      14 of 53 (26.4%) in BCS cases followed by protein C, as compared with PVT cases,
      i.e., 2 of 33 (6.06%) and controls, i.e., 5 of 223 (2.3%). In PVT cases, protein
      C deficiency was present in 3 (9.09%), protein S deficiency in 1 (3.03%), and
      factor V Leiden mutation in 2 (6.06%) of the cases. The prothrombin gene
      polymorphism was not found in either the controls or the patients. The
      antiphospholipids were seen in 11 (20.75%) of the BCS cases and 6 (18.18%) of the
      PVT cases. Other acquired risk factors like pregnancy, surgery, and oral
      contraceptives were present in 8 (15.09%) of BCS and 3 (9.09%) of PVT cases. Thus
      overall, 59% of the BCS and 30% of the PVT cases could be explained by at least
      one of the etiologic factors studied.

PMID- 11584362
TI  - Renal failure after upper gastrointestinal bleeding in cirrhosis: incidence,
      clinical course, predictive factors, and short-term prognosis.
AB  - To assess the incidence, clinical course, predictive factors, and prognosis of
      renal failure in patients with cirrhosis and gastrointestinal bleeding, 175
      consecutive episodes of gastrointestinal bleeding in 161 patients were analyzed.
      Renal failure occurred in 20 (11%) episodes and was transient in 8 episodes and
      nontransient in 12. Renal failure was more common in patients with cirrhosis than
      in a control population of bleeding patients without cirrhosis matched by age and
      severity of the bleeding episode. Among 39 clinical and laboratory variables
      obtained at admission or during hospitalization related with the bleeding episode
      or with liver and renal function, the presence of hypovolemic shock, number of
      packed red blood cells transfused, Child-Pugh class at admission, and baseline
      platelet count were independent predictors of renal failure. The development of
      renal failure and hypovolemic shock was the only independent predictors of in
      hospital mortality. Mortality rate among the 20 episodes with renal failure was
      55% (11 deaths) as compared with only 3% (5 deaths) in the 155 episodes without
      renal failure (P <.01). The development of nontransient renal failure entailed a
      much greater mortality as compared with transient renal failure (10 of 12 [83%]
      vs. 1 of 8 [12%]; P <.01). In conclusion, renal failure is a common event in
      patients with cirrhosis and gastrointestinal bleeding, the occurrence of which is
      mainly related to the severity of bleeding and baseline liver function. Renal
      failure is a strong predictor of mortality in patients with cirrhosis and
      gastrointestinal bleeding.

PMID- 11584363
TI  - Adenosine reverses a preestablished CCl4-induced micronodular cirrhosis through
      enhancing collagenolytic activity and stimulating hepatocyte cell proliferation
      in rats.
AB  - Cirrhosis is one of the most common causes of mortality worldwide, because
      hepatic dysfunction constitutes a potentially lethal condition. Having
      demonstrated the hepatoprotective effect of adenosine against CCl(4)-induced
      cirrhosis, the present study was aimed at assessing adenosine's effect on an
      already-established micronodular cirrhosis. Chronic administration of CCl(4) (10
      weeks) induced a cirrhotic state, characterized by increased liver fibronectin
      and collagen types I and III content, enhanced expression of alpha-1 (I) collagen
      mRNA, portal hypertension, and liver dysfunction. After CCl(4) discontinuation (5
      weeks), increased persitance of alpha-1 (I) collagen mRNA expression and
      deposition, enhanced proline incorporation into collagen and prolyl hydroxylase
      activity evidenced active fibrogenesis. Several weeks after CCl(4) withdrawal,
      deposited collagen showed an enhanced type I/III ratio, which was associated with
      deficient collagenolytic activity in cirrhotic livers. Liver expression of some
      metalloproteinases (MMPs) and of tissue inhibitors of MMPs (TIMPs) also indicated
      decreased collagen breakdown in cirrhotic livers. Parameters indicative of
      oxidative stress (mainly protein oxidation) were persistently augmented. These
      events were coincident with diminished regenerative capacity of the cirrhotic
      liver. Intraperitoneal adenosine administration to CCl(4)-induced cirrhotic rats
      blocked active fibrogenesis and increased the collagen degradation (most probably
      by decreasing liver TIMPs levels), normalizing collagen-type ratios. In addition,
      the nucleoside promoted an effective hepatocyte's proliferation in the cirrhotic
      liver and accelerated normalization of parameters indicative of liver function
      and oxidative stress. Thus, adenosine readily reversed an experimental cirrhosis
      through stimulating liver collagenolytic and proliferative capacities, as well as
      by accelerating functional recovery.

PMID- 11584365
TI  - Disrupted signaling and inhibited regeneration in obese mice with fatty livers:
      implications for nonalcoholic fatty liver disease pathophysiology.
AB  - The impaired regenerative capacity of fatty livers might promote the progression
      of nonalcoholic fatty liver disease (NAFLD). To identify mechanisms involved,
      regenerative responses were compared in normal mice and ob/ob mice (a model for
      NAFLD) after partial hepatectomy (PH). We hypothesized that the usual PH
      activation of oxidant-sensitive, growth-regulatory kinase cascades would be
      abnormal in fatty hepatocytes, which have adapted to chronic oxidant stress, and
      expected that this might interfere with the induction of proliferative- and
      stress-related genes. The normal coordinated induction of Jun N-terminal kinases
      (Jnks) and extracellular regulated kinases (Erks) does not occur after PH in
      ob/ob mice, which cannot activate Jnks but can superinduce Erks. Jnk inhibition
      is associated with enhanced activation of Akt, which inhibits phosphoenolpyruvate
      carboxykinase (PEPCK) induction, causing severe hypoglycemia and increased
      lethality in the ob/ob group. Activation of nuclear factor kappaB (NF-kappaB) is
      also inhibited, but liver damage is increased only modestly, perhaps because Akt
      regulated survival factors are protective. Despite enhanced Erk activity,
      induction of cyclin D-1, an NF-kappaB target gene, is abolished and this,
      together with hyperphosphorylated signal transducer and activator of
      transcription-3 (Stat-3) and reduced adenosine triphosphate (ATP) levels, arrests
      fatty hepatocytes in G(1). Thus, in mice with NAFLD that have adapted hepatocyte
      signaling mechanisms to survive chronic oxidative stress, the cellular response
      to an acute regenerative stimulus is altered. This contributes to NAFLD
      pathophysiology by inhibiting proliferation, increasing injury, and limiting
      function in fatty livers.

PMID- 11584364
TI  - The processing and utilization of hepatocyte growth factor/scatter factor
      following partial hepatectomy in the rat.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a pluripotent growth factor
      capable of acting as a motogen, a morphogen, and a mitogen. Originally, HGF/SF
      was found as a blood-borne mitogen for hepatocytes and has since been determined
      to be very important in liver repair. Previous studies have established that
      HGF/SF must be proteolytically cleaved to elicit its effects. After liver injury
      by toxins such as carbon tetrachloride or after surgical resection, partial
      hepatectomy (PHX), HGF/SF concentrations increase in the blood. The aims of this
      study were to examine (1) which form of HGF/SF is present in the normal liver,
      (2) which form is present in the regenerating liver after PHX, and (3) if the
      HGF/SF used after PHX is derived from existing liver reservoirs. Both single
      chain HGF/SF and active two-chain HGF/SF are present in normal liver, with the
      former being the dominant form. After PHX, the liver can be described as having
      two phases with regard to the use of endogenous HGF/SF. The first phase from 0 to
      3 hours is the consumptive phase and is characterized by a decrease in both
      single-chain HGF/SF and active two-chain HGF/SF. The second phase is the
      productive phase. It is characterized by a pronounced reappearance of both single
      chain HGF/SF as well as two-chain HGF/SF. The activation index shows a 5-fold
      increase over sham operations during the productive phase. The use of
      radiolabeled HGF/SF showed that during the first 3 hours, HGF/SF is used in part
      from hepatic stores. Furthermore, during the first 3 hours after PHX, only active
      two-chain HGF/SF is seen in the plasma.

PMID- 11584366
TI  - Treatment strategy for small hepatocellular carcinoma: comparison of long-term
      results after percutaneous ethanol injection therapy and surgical resection.
AB  - This comparative study was conducted to clarify the efficacy of percutaneous
      ethanol injection (PEI) and surgical resection in the treatment of small
      hepatocellular carcinomas (HCC). Thirty-nine patients treated by PEI and 58 who
      underwent hepatic resection for small HCC (smaller than 3 cm and 3 or less in
      number) during the same period were enrolled. The surgery group included more
      patients with large and multiple bilobar nodules than the PEI group. The
      histological differentiation of the treated tumors became worse in the surgery
      patients than in those treated by PEI. On the other hand, the PEI group included
      more patients with a poor hepatic reserve, according to Child-Pugh grading, the
      ICG test, and the serum total bilirubin value. The 1-, 3-, and 5-year overall
      survival rates were almost identical between the 2 cohorts (100%, 82.1%, and
      59.0%, respectively, in the PEI group; 96.6%, 84.4%, and 61.5%, respectively, in
      the surgery group) (P =.96). During the follow-up period, 33 of 39 (85%) and 41
      of 58 (71%) patients developed tumor recurrence after PEI and surgery,
      respectively. Cumulative 1-, 3-, and 5-year tumor-free survival rates in the PEI
      group were 63.4%, 30.3%, and 9.7 %, whereas those in the surgery group were
      75.5%, 44.7%, and 25.7%, respectively (P =.10). Our overall findings show that
      local therapy can achieve an actual 5-year survival rate of around 60% for
      patients with small HCC with the proper selection of treatment. A prospective
      randomized comparative trial is required to settle this longstanding issue.

PMID- 11584367
TI  - The risk of liver and bile duct cancer in patients with chronic viral hepatitis,
      alcoholism, or cirrhosis.
AB  - No prospective study has analyzed simultaneously chronic viral hepatitis and
      alcoholism as risk factors for liver carcinogenesis, while taking into
      consideration the role of cirrhosis. Nor has the risk for hepatocellular
      carcinoma among patients with chronic viral hepatitis been prospectively
      evaluated in a low-risk Western population. Last, the relationship between
      hepatocellular carcinoma risk factors and bile duct cancer remains to be
      clarified. We analyzed prospectively the risk for primary liver and extrahepatic
      biliary tract cancer among 186,395 patients hospitalized with either chronic
      viral hepatitis, alcoholism, cirrhosis, or any combination of these conditions
      through linkages between national Swedish registers. Compared with the general
      population, the relative risk of hepatocellular carcinoma was 34.4 for chronic
      viral hepatitis alone, 2.4 for alcoholism alone, and 40.7 for cirrhosis alone.
      Among patients with combinations of these risk conditions, the relative risk of
      hepatocellular carcinoma was 27.3 for chronic viral hepatitis and alcoholism,
      118.5 for chronic viral hepatitis and cirrhosis, 22.4 for alcoholism and
      cirrhosis, and 171.4 for all 3 conditions. We found limited evidence for an
      excess risk of intrahepatic, but not for extrahepatic, biliary duct cancer.
      Cirrhosis amplifies the risk of hepatocellular carcinoma among patients with
      chronic viral hepatitis, but it is not a prerequisite for liver carcinogenesis.
      In contrast, cirrhosis may be a necessary intermediate for the development of
      hepatocellular carcinoma among alcoholics.

PMID- 11584368
TI  - Targeting dexamethasone to Kupffer cells: effects on liver inflammation and
      fibrosis in rats.
AB  - Kupffer cells (KC) play an important role in the pathogenesis of inflammatory
      liver diseases leading to fibrosis. Anti-inflammatory drugs are only effective
      when administered at high doses that may cause side effects. Therefore,
      dexamethasone coupled to mannosylated albumin (Dexa(5)-Man(10)-HSA) was designed
      by us to selectively deliver this anti-inflammatory drug to the KC. The
      effectiveness of Dexa(5)-Man(10)-HSA was studied both in organ cultures and
      fibrosis induced by bile duct ligation (BDL) in rats. Dexa(5)-Man(10)-HSA
      accumulated in livers of both healthy and fibrotic rats (67% +/- 5% and 70% +/-
      9% of the dose, respectively) and uptake was found almost exclusively in KC.
      Active dexamethasone was liberated from its carrier, because Dexa(5)-Man(10)-HSA
      could effectively inhibit nitric oxide (NO) and tumor necrosis factor alpha (TNF
      alpha) release in endotoxin-activated liver slices. In vivo, however, this was
      associated with increased collagen I and III depositions and enhanced tissue
      inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression. This was accompanied
      by a decreased influx of reactive oxygen species (ROS) producing cells in the
      livers of BDL animals treated with Dexa(5)-Man(10)-HSA as compared with untreated
      BDL rats. Dexa(5)-Man(10)-HSA treatment also replenished the depleted glycogen
      stores in hepatocytes of BDL livers. In conclusion, our studies showed selective
      delivery of dexamethasone to KC with Dexa(5)-Man(10)-HSA. This conjugate reduced
      intrahepatic ROS in vivo and TNF-alpha production in vitro and prevented glycogen
      depletion in vivo, indicating effective pharmacologic targeting. Dexa(5)-Man(10)
      HSA, however, also accelerated fibrogenesis, which was paralleled by TIMP-1 mRNA
      induction. Targeting of dexamethasone to KC provides evidence for a dual role of
      this cell type in fibrogenesis of BDL rats.

PMID- 11584369
TI  - Oxidized low-density lipoproteins bind to the scavenger receptor, CD36, of
      hepatic stellate cells and stimulate extracellular matrix synthesis.
AB  - Cumulating evidence suggests that oxidative stress resulting in lipid
      peroxidation and protein modification is involved in the pathogenesis of chronic
      liver injury and fibrogenesis. We investigated the effects of oxidized low
      density lipoproteins (oxLDL) on collagen and fibronectin synthesis of cultured
      human and rat hepatic stellate cells (HSC). As shown on protein and mRNA levels,
      oxLDL dose-dependently stimulated the synthesis of collagen types I and III and
      fibronectin of cultured HSC. The effect was biphasic, with a maximum between 5
      and 25 microg/mL oxLDL (c-fibronectin concentration in HSC supernatants increased
      3.9-fold; collagen type I increased 4-fold). Higher oxLDL concentrations were
      cytotoxic. LDL modified with malondialdehyde (MDA) was not toxic, but stimulated
      extracellular matrix synthesis as well. As demonstrated by immunofluorescence
      microscopy (double staining of CD36 and iso-alpha-smooth muscle actin [iso-alpha
      sm actin]), immunoblot, and reverse-transcription polymerase chain reaction (RT
      PCR), respectively, cultured human HSC express the oxLDL receptor, CD36
      (glycoprotein IIIb). Colocalization of CD36 and iso-alpha-sm actin on sinusoidal
      lining cells was further demonstrated using sections of human fibrotic liver.
      Preincubation of cultured human HSC with the monoclonal antibody, OKM5, known to
      block CD36-mediated oxLDL uptake, resulted in a reduction of the oxLDL-stimulated
      collagen type I synthesis by 56%. In summary, our results demonstrate that low
      concentrations of modified lipoproteins (oxLDL and MDA-LDL) represent fibrogenic
      mediators that bind to CD36 and stimulate matrix synthesis of HSC.

PMID- 11584370
TI  - High glucose and hyperinsulinemia stimulate connective tissue growth factor
      expression: a potential mechanism involved in progression to fibrosis in
      nonalcoholic steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) may progress to liver fibrosis and cirrhosis.
      Mechanisms directly involved in the development of fibrosis have been poorly
      investigated. Because connective tissue growth factor (CTGF) is an intermediate
      key molecule involved in the pathogenesis of fibrosing chronic liver diseases and
      is potentially induced by hyperglycemia, the aims of this study were to (1) study
      the expression of CTGF in vivo both in human liver biopsy specimens of patients
      with NASH and in an experimental model of obesity and type II diabetes (Zucker
      rats); and (2) analyze the effects of hyperglycemia and insulin in vitro on
      hepatic stellate cells. In vivo, CTGF overexpression was observed in the liver
      tissue of all of the 16 patients with NASH. CTGF immunostaining was mild in 7
      cases (44%) and moderate or strong in 9 cases (56%). Staining was mainly detected
      in the liver extracellular matrix in parallel with the amount of liver fibrosis.
      Liver from fa/fa rats also showed CTGF overexpression by comparison with Fa/fa
      rats both at the messenger RNA (mRNA) level (3-fold increase) and protein level.
      In vitro, both CTGF mRNA and protein were significantly increased when hepatic
      stellate cells were incubated with either glucose or insulin. A slight increase
      in type I procollagen mRNA level was also observed in hepatic stellate cells
      incubated with glucose. In conclusion, this study suggests that hyperglycemia and
      insulin are key-factors in the progression of fibrosis in patients with NASH
      through the up-regulation of CTGF.

PMID- 11584371
TI  - Angiotensin-II type 1 receptor interaction is a major regulator for liver
      fibrosis development in rats.
AB  - The renin-angiotensin system (RAS) is frequently activated in patients with
      chronic liver diseases. Angiotensin-II (AT-II) has been suggested to play an
      important role in liver fibrogenesis. It induces hepatic stellate cell (HSC)
      proliferation and up-regulates the transforming growth factor beta(1) (TGF
      beta(1)) expression via AT-II type 1 receptor (AT(1)-R) in vitro. The aim of the
      present study was to examine the in vivo effect of candesartan (CA), a clinically
      used AT(1)-R blocker (ARB), and perindopril (PE), an angiotensin-converting
      enzyme (ACE) inhibitor (ACE-I), on pig serum-induced liver fibrosis development
      in rats. The clinically available comparable doses of CA and PE significantly
      attenuated the fibrosis development. These inhibitory effects of PE and CA were
      also found in the on-going liver fibrosis model. The hepatic hydroxyproline and
      serum fibrosis markers were significantly suppressed by CA and PE treatment.
      Furthermore, the alpha smooth muscle actin (alpha-SMA) positive cells in number
      were markedly suppressed by CA and PE treatment. Similarly, the hepatic TGF
      beta(1) protein and messenger RNA (mRNA) levels were significantly suppressed.
      Our in vitro study showed that AT-II increased the TGF-beta(1) mRNA expression in
      the activated HSCs, and this effect was totally blocked by CA. These results
      suggested that the RAS, especially AT-II and AT(1)-R interaction plays a pivotal
      role in liver fibrosis development through HSC activation. Because both CA and PE
      are widely used in clinical practice without serious side effects, these drugs
      may provide an effective new strategy for anti-liver fibrosis therapy.

PMID- 11584372
TI  - Enhanced expression of B7-1, B7-2, and intercellular adhesion molecule 1 in
      sinusoidal endothelial cells by warm ischemia/reperfusion injury in rat liver.
AB  - To elucidate a role of costimulatory molecule and cell adhesion molecule in
      hepatic ischemia/reperfusion injury, we examined an alteration in B7-1 (CD80), B7
      2 (CD86), and intercellular adhesion molecule 1 (ICAM-1; CD54) expression in the
      rat liver after warm ischemia/reperfusion injury. To induce hepatic warm ischemia
      in a rat model, both portal vein and hepatic artery entering the left-lateral and
      median lobes were occluded by clamping for 30 minutes or 60 minutes, and then
      reperfused for 24 hours. B7-1, B7-2, and ICAM-1 expressions in the liver were
      analyzed by immunofluorescence staining and real-time reverse transcription
      polymerase chain reaction (RT-PCR). Although B7-1 and B7-2 expressions were at
      very low levels in the liver tissues from normal or sham-operated control rats,
      both B7-1 and B7-2 expressions were enhanced at protein and messenger RNA (mRNA)
      levels in the affected, left lobes after warm ischemia/reperfusion. ICAM-1
      protein and mRNA were constitutively expressed in the liver of normal and sham
      operated control rats, and further up-regulated after warm ischemia/reperfusion.
      Localization of increased B7-1, B7-2, and ICAM-1 proteins, as well as von
      Willebrand factor as a marker protein for endothelial cells, was confined by
      immunofluorescence staining to sinusoidal endothelial cells in hepatic lobules.
      Data from quantitative real-time RT-PCR analysis revealed that B7-1 and B7-2 mRNA
      levels were elevated in hepatic lobes after warm ischemia/reperfusion (5.13- and
      52.9-fold increase, respectively), whereas ICAM-1 mRNA expression was rather
      constitutive but further enhanced by warm ischemia/reperfusion (4.24-fold
      increase). These results suggest that hepatic sinusoidal endothelial cells play a
      pivotal role as antigen-presenting cells by expressing B7-1 and B7-2 in warm
      hepatic ischemia/reperfusion injury, and that B7-1 and/or B7-2 might be the
      primary target to prevent early rejection and inflammatory reactions after
      hepatic ischemia/reperfusion injury associated with liver transplantation.

PMID- 11584373
TI  - Caspase activation correlates with the degree of inflammatory liver injury in
      chronic hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection is a major cause of liver disease characterized
      by inflammation, cell damage, and fibrotic reactions of hepatocytes. Apoptosis
      has been implicated in the pathogenesis, although it is unclear whether proteases
      of the caspase family as the central executioners of apoptosis are involved and
      how caspase activation contributes to liver injury. In the present study, we
      measured the activation of effector caspases in liver biopsy specimens of
      patients with chronic HCV infection. The activation of caspase-3, caspase-7, and
      cleavage of poly(ADP-ribose)polymerase (PARP), a specific caspase substrate, were
      measured by immunohistochemistry and Western blot analysis by using antibodies
      that selectively detect the active truncated, but not the inactive precursor
      forms of the caspases and PARP. We found that caspase activation was considerably
      elevated in liver lobules of HCV patients in comparison to normal controls.
      Interestingly, the immunoreactive cells did yet not reveal an overt apoptotic
      morphology. The extent of caspase activation correlated significantly with the
      disease grade, i.e., necroinflammatory activity. In contrast, no correlation was
      observed with other surrogate markers such as serum transaminases and viral load.
      In biopsy specimens with low activity (grade 0) 7.7% of the hepatocytes revealed
      caspase-3 activation, whereas 20.9% of the cells stained positively in grade 3.
      Thus, our results suggest that caspase activation is involved in HCV-associated
      liver injury. Moreover, measurement of caspase activity may represent a reliable
      marker for the early detection of liver damage, which may open up new diagnostic
      and therapeutic strategies in HCV infection.

PMID- 11584374
TI  - Familial intrahepatic cholestasis 1: studies of localization and function.
AB  - Mutations in the FIC1 gene constitute the molecular defect in familial
      intrahepatic cholestasis I (Fic1 [Byler's disease]) and benign recurrent
      intrahepatic cholestasis. This report describes the localization of Fic1 in rat
      liver and intestine, as well as biochemical and transfection studies that support
      its function as an energy-dependent aminophospholipid translocase.
      Immunocytochemistry of rat liver and immunoblotting of membrane fractions
      localized Fic1 to the canalicular, but not basolateral, plasma membrane domain.
      In the small intestine, Fic1 was localized to the apical membrane of epithelial
      cells. The distribution of Fic1 in liver plasma membrane fractions from control
      and taurocholate-treated rats correlated positively with adenosine triphosphate
      (ATP)-dependent aminophospholipid (phosphatidyl-serine) translocase activity. In
      canalicular membrane vesicles, translocase activity had an initial velocity of
      3.3 nmol phosphatidylserine (PS) translocated per milligram of protein per minute
      and a K(m) (ATP) = 1.2 mmol/L; was inhibited by vanadate, N-ethylmaleimide,
      sodium azide, and calcium; and was unidirectional (i.e., from the outer to the
      inner canalicular plasma membrane leaflet). Transient transfection of CHOK1 cells
      with FIC1 cDNA resulted in appearance of FIC1 in membrane preparations and energy
      dependent PS translocation in cells. These studies indicate that FIC1 is a
      canalicular P-type ATPase that participates in maintaining the distribution of
      aminophospholipids between the inner and outer leaflets of the plasma membrane.
      How this process produces cholestasis is under study.

PMID- 11584375
TI  - The hepatic mitochondrial DNA depletion syndrome: ultrastructural changes in
      liver biopsies.
AB  - Mitochondrial respiratory chain disorders are an established cause of liver
      failure in early childhood. In some patients, the levels of mitochondrial DNA are
      markedly reduced, a condition referred to as mtDNA depletion syndrome (MDS). We
      report here on the ultrastructural changes in the livers of 10 infants with the
      hepatic form of this syndrome. All patients displayed progressive liver failure,
      neurological abnormalities, hypoglycemia, and lactic acidosis that warranted
      investigation of respiratory chain disorder in liver tissue, specifically
      expressing the disease. Decreased activity of respiratory chain complexes
      containing mtDNA-encoded subunits (complexes I, III, IV) was shown in 5 patients.
      Mitochondrial DNA depletion was confirmed by Southern blot analysis in the livers
      of 6 patients. We found hepatocytes filled with mitochondria having aspects of
      "oncocytic transformation," associated with numerous changes in shape, size,
      cristae, and matrix. The changes were virtually identical in all specimens. In
      many hepatocytes, microvesicular steatosis was the salient feature. Additional
      findings included cholestasis and focal cytoplasmic biliary necrosis (CBN), as
      well as cytosiderosis in hepatocytes and sinusoidal cells. In some hepatocytes
      the damage appeared extreme, but fibrosis was identified only in the few patients
      who died beyond 6 months of age. Although individual ultrastructural findings are
      not specific, when taken together, they show a diagnostic pattern highly
      suggestive of a respiratory chain disorder. In the appropriate clinical context,
      these findings can direct the clinician towards the diagnosis of hepatic MDS.

PMID- 11584376
TI  - Factors associated with hepatitis B virus DNA breakthrough in patients receiving
      prolonged lamivudine therapy.
AB  - Factors associated with hepatitis B virus (HBV) DNA breakthrough and the
      significance of YMDD variants without the presence of wild-type YMDD during
      prolonged lamivudine treatment are unknown. We studied the amino acid sequence of
      codon 552 (YMDD motif) and codon 528 by means of a line probe assay in 159
      chronic HBV patients (median follow-up 29.6 months). Pretreatment HBV DNA levels
      and alanine transaminase (ALT) levels correlated inversely with the time to HBV
      DNA breakthrough with YMDD variants (r = -0.46, P =.001; r = -0.45, P =.001
      respectively). Patients harboring YMDD variants 3 months before HBV DNA
      breakthroughs had higher HBV DNA breakthrough levels compared with those without
      YMDD variants 3 months before HBV DNA breakthroughs (18.9 x 10(6) vs. 5.4 x 10(6)
      copies/mL, P =.007). Patients with HBV DNA breakthroughs had higher percentages
      of YMDD variants without the presence of wild-type YMDD compared with patients
      without HBV DNA breakthrough (25.6% vs. 9%, P =.007 for single M552I variant;
      20.9% vs. 8.1%, P =.026 for single M552V variant; 30.2% vs. 9.9%, P =.004 for
      M552I/M552V variants). Patients with HBV DNA levels of more than 10(3) copies/mL
      after 6 months of lamivudine therapy had a 63.2% chance of subsequently
      developing YMDD variants. HBeAg seroconversion occurred in 2 patients after the
      emergence of YMDD variants. Only one patient developed YMDD variant after HBeAg
      seroconversion. There was no increase in the rate of development of YMDD variants
      or L528M mutation in patients receiving lamivudine 25 mg daily or famciclovir 500
      mg 3 times a day before being given lamivudine 100 mg daily.

PMID- 11584377
TI  - Chronic ethanol consumption stimulates hepatitis B virus gene expression and
      replication in transgenic mice.
AB  - Epidemiologic observations show a higher frequency of hepatitis B virus (HBV)
      serologic markers in chronic alcoholics compared with the general population.
      This may be the result of an increased susceptibility of alcoholics to infection
      and/or to an ethanol-mediated stimulation of HBV gene expression and replication.
      To test the latter hypothesis, HBV transgenic SCID mice, which support consistent
      levels of virus replication, were fed with a standard Lieber-DiCarli or
      isocaloric diet for 5 weeks. In ethanol-fed mice, the levels of hepatitis B
      surface antigen (HBsAg) and viral DNA in serum increased by up to 7-fold compared
      with mice fed the control diet. Ethanol-treated mice also had elevated HBV-RNA
      levels, and increased expression of surface, core, and X antigens in the liver,
      especially in the pericentral regions. None of these changes were observed in
      transgenic mice fed isocaloric diets. Thus, chronic alcohol consumption alters
      the patterns of HBV gene expression and replication in the serum and liver of HBV
      transgenic SCID mice, and may provide a partial explanation for the increased
      frequency of HBV markers among alcoholics.

PMID- 11584378
TI  - Evaluation of a new hepatitis B triple-antigen vaccine in inadequate responders
      to current vaccines.
AB  - In this double-blind, randomized, controlled study, healthcare professionals with
      a history of inadequate response to currently available single-antigen hepatitis
      B vaccines confirmed by measuring hepatitis B surface antibody titer before entry
      to the study were revaccinated with a 20-microg dose either of a novel triple
      antigen (S, pre-S1, and pre-S2) recombinant vaccine or of a present single
      antigen (S only) vaccine. Hepatitis B surface antibody titers were measured 8
      weeks' post revaccination. A total of 925 individuals were randomized and
      vaccinated, of whom 915 (98.9%) completed the study and were included in the
      efficacy analysis. A single dose of the new triple-antigen hepatitis B vaccine
      (Hepacare) produced a successful response in over three quarters of these
      subjects who had not mounted an adequate response to current vaccines. The
      antibody response was statistically significantly superior (P =.002) to that
      after a single dose of current vaccines. An evaluation of the overall response
      showed that only the triple-antigen vaccine was able to raise the average
      antibody response (geometric mean titer [GMT]) to over 100 IU/L. The superior
      effect of the new vaccine was most pronounced in subjects who were previously
      complete nonresponders to currently available hepatitis B vaccines. Both vaccines
      were well tolerated and had similar safety profiles. This study demonstrated that
      in healthcare workers who had responded inadequately to at least a full course of
      immunization (median, 5 doses), a single 20-microg dose of a new triple-antigen
      vaccine induced protective antibody level in more vaccinees (P =.002) and
      increased the average antibody titer (GMT) in those protected successfully to a
      greater degree (P <.001) than a further attempt with a current vaccine (Engerix
      B).

PMID- 11584379
TI  - Endothelial cell-mediated uptake of a hepatitis B virus: a new concept of liver
      targeting of hepatotropic microorganisms.
AB  - The liver is a target for many infectious agents, most notably hepatitis viruses.
      However, several receptor molecules identified so far for hepatitis viruses were
      found to be ubiquitously expressed and can thus not account for efficient liver
      targeting. Using a model hepatitis B virus, the duck hepatitis B virus (DHBV), we
      have obtained data indicating that scavenging liver sinusoidal endothelial cells
      (LSEC), rather than hepatocytes themselves, play the key role in the initial
      uptake of viral pathogens into the liver. Experiments with fluorescent viral
      particles and coated gold particles in test animals, as well as in primary liver
      cell culture, demonstrated a preferential uptake of the viral substrates into
      LSEC. Intracellularly, fluorescent virus particles internalized by LSEC
      colocalized with the DHBV receptor, carboxypeptidase D, suggesting receptor
      mediated rescue from lysosomal degradation. To comply with the high efficiency by
      which hepatitis B viruses infect hepatocytes in vivo, we propose that viruses
      initially scavenged by LSEC are thereafter released to infect adjacent
      hepatocytes, the only cells capable of replicating these viruses. Such a model of
      primary uptake into LSEC may illustrate a general mechanism by which blood-borne
      hepatotropic agents are targeted to the hepatocytes in the liver.

PMID- 11584380
TI  - Estimating progression to cirrhosis in chronic hepatitis C virus infection.
AB  - To gain a clearer understanding of the rate of progression to cirrhosis and its
      determinants in chronic hepatitis C virus (HCV) infection, a systematic review of
      published epidemiologic studies that incorporated assessment for cirrhosis has
      been undertaken. Inclusion criteria were more than 20 cases of chronic HCV
      infection, and information on either age of subjects or duration of infection. Of
      145 studies examined, 57 fulfilled the inclusion criteria. Least-squares linear
      regression was employed to estimate rates of progression to cirrhosis, and to
      examine for factors associated with more rapid disease progression in 4 broad
      study categories: 1) liver clinic series (number of studies = 33); 2)
      posttransfusion cohorts (n = 5); 3) blood donor series (n = 10); and 4) community
      based cohorts (n = 9). Estimates of progression to cirrhosis after 20 years of
      chronic HCV infection were 22% (95% CI, 18%-26%) for liver clinic series, 24%
      (11%-37%) for posttransfusion cohorts, 4% (1%-7%) for blood donor series, and 7%
      (4%-10%) for community-based cohorts. Factors that were associated with more
      rapid disease progression included older age at HCV infection, male gender, and
      heavy alcohol intake. Even after accounting for these factors, progression
      estimates were much higher for cross-sectional liver clinic series. Selection
      biases probably explain the higher estimates of disease progression in this group
      of studies. Community-based cohort studies are likely to provide a more
      representative basis for estimating disease progression at a population level.
      These suggest that for persons who acquire HCV infection in young adulthood, less
      than 10% are estimated to develop cirrhosis within 20 years.

PMID- 11584381
TI  - Acute exacerbations of chronic hepatitis B are rarely associated with
      superinfection of hepatitis B virus.
AB  - There are 7 genotypes of hepatitis B virus (HBV). Whether superinfection of HBV
      carriers with different HBV genotypes occurs remains unknown. We therefore
      determined the HBV genotype and association between superinfection and acute
      exacerbation of disease in a cohort of 244 patients with chronic HBV infection
      who had elevated serum aminotransferase levels for at least 1 year. Within this
      group, 103 patients experienced acute exacerbation with an annual incidence of
      13%, and 20 of the 103 patients had IgM antibody to hepatitis B core antigen (IgM
      anti-HBc). These 20 patients had a higher prevalence of genotype C infection
      (65%) than the remaining 83 anti-core IgM-negative patients (40%) who also had
      acute exacerbations (P <.05). Detailed analysis of HBV genotypes and sequences of
      the variable pre-S gene were determined in serial samples from 20 patients with
      IgM anti-HBc-positive acute exacerbations (group A), 20 patients with IgM anti
      HBc-negative acute exacerbations (group B), and 20 patients without exacerbations
      (group C). Two (10%) of the group A patients had virologic evidence of HBV
      superinfection during acute exacerbation, one superinfected with heterotypic
      virus and the other with homotypic virus. The newly introduced virus disappeared
      after the exacerbation and the original virus resumed thereafter. The calculated
      prevalence of HBV superinfection in the hepatitis B carriers and those with acute
      exacerbations was 0.8% (2 of 244) and 1.9% (2 of 103), respectively. In
      conclusion, superinfection of HBV on hepatitis B carriers indeed occurs and may
      cause acute exacerbations, albeit at a low frequency even in hyperendemic areas
      of HBV infection.

PMID- 11584382
TI  - Woodchuck hepatocytes remain permissive for hepadnavirus infection and mouse
      liver repopulation after cryopreservation.
AB  - Isolated hepatocytes represent a relevant model of the liver and are highly
      required both for research and therapeutic applications. However, sources of
      primary liver cells from human beings and from some animal species are limited.
      Therefore, cryopreservation of hepatocytes could greatly facilitate advances in
      various research areas. The aim of this study was to evaluate whether
      cryopreserved primary woodchuck hepatocytes could be used for woodchuck hepatitis
      B virus (WHV) infection studies, and whether they could maintain their
      regenerative potential in vivo after thawing. Critical steps for good quality of
      cryopreserved hepatocytes included the use of University of Wisconsin (UW)
      solution as a main component of the freezing medium, stepwise reduction of
      dimethylsulfoxide (DMSO) to avoid osmotic shock, and maintenance of low
      concentrations of DMSO in the culture medium. After cryopreservation, cell
      viability was still high (70% to 80%), and 50% to 60% of thawed cells attached to
      the plates. The appearance of covalently closed circular (ccc)DNA and of WHV
      replicative forms a few days after in vitro infection demonstrated that thawed
      woodchuck hepatocytes were still susceptible to viral infection, thus proving
      maintenance of a very high hepatocyte-specific differentiation status.
      Furthermore, transplantation of woodchuck hepatocytes into the liver of urokinase
      type plasminogen activator (uPA)/recombination activation gene-2 (RAG-2) mice, a
      model of liver regeneration, demonstrated that cryopreserved cells retained the
      ability to divide and to extensively repopulate a xenogenic liver. Notably, in
      vivo susceptibility to infection with WHV and proliferative capacity of
      frozen/thawed woodchuck hepatocytes in recipient mice were identical to those
      observed by transplanting fresh hepatocytes.

PMID- 11584383
TI  - Pharmacologic treatment of portal hypertension: past, present, and future.

PMID- 11584384
TI  - Towards a reliable parameter of liver damage in hepatitis C: TUNEL versus caspase
      activation.

PMID- 11584385
TI  - NAFLD and NASH: important diseases before and after liver transplantation.

PMID- 11584386
TI  - TNF toxicity--death from caspase or cathepsin, that is the question.

PMID- 11584387
TI  - Blind beta blockade.

PMID- 11584388
TI  - Bile secretion in mice and men.

PMID- 11584389
TI  - Schistosomiasis and antiviral treatment of chronic hepatitis C.

PMID- 11584390
TI  - Inflammatory myopathy and hepatitis C in a pediatric patient: role of liver
      biopsy in evaluating the severity of liver disease.

PMID- 11584391
TI  - The cost-effectiveness of neonatal surgery and subsequent treatment for
      congenital anorectal malformations.
AB  - BACKGROUND/PURPOSE: The progress made in all fields of medicine, including
      neonatal surgery, has contributed to the rise in healthcare costs. Although
      neonatal surgery may provide survival gains, these could be at the expense of
      worse quality of life caused by impairment after surgery. For example, congenital
      anorectal malformations (CAM) are complex anomalies, and the surgical techniques
      available have their limitations in achieving continence. It therefore seems
      justifiable to consider what the effects of treatment are in relation to the
      costs. Evidence of the cost-effectiveness of neonatal surgery, however, is
      lacking. METHODS: The authors analyzed both direct and indirect, medical and
      nonmedical costs in patients who had undergone treatment for CAM. Quality
      adjusted life years (QALYs) were measured using the EuroQol EQ-5D questionnaire.
      Descriptive quality-of-life data were collected using a disease-specific
      questionnaire and a medical consumption questionnaire. RESULTS: Mean costs of
      treatment are calculated at Euro 31,593. Treated CAM patients suffer stool
      difficulties and their medical consumption is relatively high. The EQ-5D,
      however, shows that the quality of life of CAM patients is only slightly lower
      than that of the general population (0.88 v 0.93). Treatment results in a gain of
      12.7 QALYs. Costs per QALY of treatment for CAM amount to Euro 2,482.
      CONCLUSIONS: Treatment for CAM has a favorable cost-effectiveness ratio compared
      with other evaluated healthcare programs. Bearing in mind the increasing
      political interest in evidence-based and cost-effective medicine, the results are
      encouraging.

PMID- 11584392
TI  - Outcome of infants with bronchopulmonary dysplasia who receive extracorporeal
      membrane oxygenation therapy.
AB  - BACKGROUND/PURPOSE: Extracorporeal membrane oxygenation (ECMO) is an accepted
      therapy for acute respiratory failure but more recently has been used in infants
      with bronchopulmonary dysplasia (BPD) and superimposed acute pulmonary insults.
      The purpose of this study was to review the outcomes of such infants. METHODS:
      Charts of infants at The Children's Hospital of Philadelphia (CHOP) who had a
      diagnosis of BPD before ECMO were reviewed. In addition, to obtain survival data
      in a larger population, the Extracorporeal Life Support Organization (ELSO)
      Registry was searched for infants with BPD before ECMO. RESULTS: Of 204 patients
      who received noncardiac ECMO at CHOP, 9 had BPD before ECMO. Of 7 survivors, 4
      were still ventilator dependent at 9 to 39 months of corrected age.
      Developmentally, 4 had significant global delays, whereas 3 had significant
      language and motor delays with average to mildly delayed cognitive abilities. The
      ELSO Registry search showed 76 patients with BPD before ECMO, with a 78%
      survival. CONCLUSIONS: The survival rate of infants with BPD who receive ECMO is
      comparable to, or better than, the survival rates in most other ECMO populations.
      However, there appears to be a high risk of severe pulmonary and
      neurodevelopmental sequelae.

PMID- 11584393
TI  - The incidence of septic complications in newborns on extracorporeal membrane
      oxygenation is not affected by feeding route.
AB  - PURPOSE: The aim of this study was to compare the effects of enteral and total
      parenteral feeding on septic complications in neonates on extracorporeal membrane
      oxygenation (ECMO). METHODS: Ninety-six neonates were on ECMO between January
      1992 and February 1998. Matching for diagnosis and exclusion of neonates with
      sepsis before ECMO or undergoing surgery on ECMO left 16 enterally fed neonates
      (cases) and 35 parenterally fed neonates (controls) for analysis. Septic
      complications were scored using the criteria of the Society of Critical Care
      Medicine and the American College of Chest Physicians adapted to children.
      RESULTS: Both groups were comparable with respect to gestational age, sex, and
      age at initiation of ECMO. The frequency of septic complications did not differ
      between cases and controls: no complications, 75% versus 69%; systemic
      inflammatory response syndrome, 13% versus 6%; bacteremia, 6% versus 14%; sepsis,
      6% versus 11%. There were no complications associated with enteral feeding. The
      ECMO run was significantly longer in the case group (median, 161 v. 111 hours; P
      =.01) and mortality rate was lower in the case group (0 v. 14%; P =.17).
      CONCLUSIONS: Enteral nutrition does not affect the risk of sepsis in neonates on
      ECMO when compared with total parenteral nutrition. Enteral nutrition is well
      tolerated and not associated with adverse effects.

PMID- 11584394
TI  - Decreased mitogen activated protein kinase activities in congenital diaphragmatic
      hernia-associated pulmonary hypoplasia.
AB  - BACKGROUND/PURPOSE: The mechanisms that cause pulmonary hypoplasia associated
      with congenital diaphragmatic hernia (CDH) currently are unknown. The authors
      proposed that the reduced size and immaturity of these lungs may be associated
      with differences in the levels of mitogen activated protein (MAP) kinase
      phosphorylation (extracellular signal regulated protein kinases, ERK-1 and -2).
      METHODS: ERK-1 activities were measured using immune-complex kinase assays on
      fetal whole-lung lysates obtained from both nitrofen and olive oil-treated
      (control) pregnant rats. In addition, ERK-1 and ERK-2 functional activities were
      estimated by semiquantitative Western blot analysis, using an antibody specific
      for the diphosphorylated (dp-ERK, activated) forms of the enzymes. RESULTS: ERK-1
      activities, measured using immune-complex kinase assays, were reduced in CDH
      lungs compared with olive oil-treated controls (P <.02). In addition, dp-ERK-1
      and dp-ERK-2 levels were found to be reduced in CDH lungs compared with controls
      (dp-ERK-1, P =.003; dp-ERK-2, P =.04), whereas ERK-1 and ERK-2 protein levels
      were unchanged. CONCLUSIONS: The lower values of ERK-1 activity and reduced
      amounts of dp-ERK-1 and dp-ERK-2 in lung tissue from CDH animals, suggests that
      ERK-1 and ERK-2 activities are reduced in pulmonary hypoplasia associated with
      CDH. The observed reduction in ERK-1 and ERK-2 activities implicates attenuated
      cell signaling upstream of the ERK-1 and -2 enzymes.

PMID- 11584395
TI  - Cardiac gene expression and synthesis of atrial natriuretic peptide in the
      nitrofen model of congenital diaphragmatic hernia in rats: effect of prenatal
      dexamethazone treatment.
AB  - BACKGROUND/PURPOSE: The aim of this study was to determine the gene and protein
      levels of atrial natriuretic peptide (ANP) in the heart of nitrofen-induced
      congenital diaphragmatic hernia (CDH) in rats and to evaluate the effect of
      antenatal dexamethazone (Dex) treatment. METHODS: CDH model was induced in
      pregnant rats after administration of 100 mg of nitrofen on day 9.5 of gestation
      (term, day 22). Dexamethazone (Dex, 0.25 mg/kg) was given by intraperitoneal
      injection on days 18.5 and 19.5 of gestation. Cesarean section was performed on
      day 21 of gestation. The fetuses were divided into 3 groups: group I, control (n
      = 10); group II, nitrofen-induced CDH (n = 10); group III, nitrofen-induced CDH
      with antenatal Dex treatment (n = 10). ANP protein was measured using enzyme
      linked immunosorbent assay (ELISA) technique. Reverse transcription polymerase
      chain reaction (RT-PCR) was performed to evaluate the relative amount of atrial
      natriuretic peptide (ANP) mRNA expression. RESULTS: There was a significant
      reduction in ANP mRNA (P <.05) and protein (P <.01) levels in heart of group II
      (CDH) compared with group I. Antenatal Dex treatment significantly increased both
      ANP mRNA and protein levels in the heart of CDH animals (P <.05). CONCLUSIONS:
      The reduced cardiac ANP gene expression and ANP synthesis indicates that the
      heart in CDH is functionally immature and may be unable to respond to hemodynamic
      load accompanying persistent pulmonary hypertension (PPH). ANP or drugs such as
      steroids, which raise endogenous ANP levels, may have a therapeutic application
      in CDH complicated by PPH.

PMID- 11584396
TI  - Aortopexy in esophageal atresia: long-term experience of a parent support group.
AB  - PURPOSE: The aim of this study was to obtain the parents' view of aortopexy after
      esophageal atresia. METHODS: A questionnaire was completed by the parents of 24
      former patients, now aged from 1 to 15 years (average, 8.9; median, 9.0 years).
      The respondents were all members of a support group. RESULTS: The median age of
      the patients receiving aortopexy was 4 months. The 24 procedures were performed
      in 16 different hospitals. The subjects had experienced a median of 3 apneic
      attacks. Technical complications occurred in 4 of the 24 children. In 71%,
      aortopexy was an immediate success. CONCLUSION: Despite its low success rate
      compared with centers with large cumulative experience, 90% of parents were
      satisfied with the result.

PMID- 11584397
TI  - Effects of caffeic acid phenethyl ester and epidermal growth factor on the
      development of caustic esophageal stricture in rats.
AB  - BACKGROUND/PURPOSE: An experimental study was performed to modify the healing
      response in caustic esophageal burns to prevent stricture development. Two
      different agents with different modes of actions, caffeic acid phenethyl ester
      (CAPE) and epidermal growth factor (EGF), were studied. CAPE has
      antiinflammatory, immunomodulatory, antioxidant, and antimitotic properties. EGF
      has known properties in supporting wound healing and in protecting esophagus from
      injuries. METHODS: The model described by Gehanno and its modification by Liu was
      used to create standard esophageal burns with 50% NaOH. The study was performed
      with 76 rats in 4 main groups (sham, CAPE, EGF, and control) and 2 subgroups in
      each for 5 and 28 days of observation. Efficacy of treatment was assessed in 28
      day subgroups by measuring weight gain, contrast esophagograms on day 27,
      histologic evaluation by measuring stenosis index (wall thickness/lumen
      diameter), and collagen deposition, and biochemically by determining tissue
      hydroxy proline (OHP) content. RESULTS: In the end of the study, increase rates
      of mean body weights of the animals in the 28-day subgroups were as follows:
      sham, 30%; CAPE, 23%; EGF, 22%; and control, 14%. Although all the animals in
      subgroups significantly gained weight, the mean weight gain was significantly low
      in controls when compared with sham, CAPE, and EGF groups (P <.05). Contrast
      esophagograms on day 27 showed no stenosis in the sham, mild stenosis in CAPE and
      EGF, and severe stenosis with proximal dilatation in controls. Stenosis indices
      of the subgroups were as follows: sham, 0.29; CAPE, 0.41; EGF, 0.41; control,
      0.84. Index was significantly higher in controls (P <.05). Collagen accumulation
      scores in the esophageal wall were as follows: Sham, 0.0; CAPE, 0.87; EGF, 0.30;
      control, 2.70. Scores also were significantly higher in controls (P <.05). Tissue
      (OHP) levels were as follows (mg/g dry tissue): Sham, 1.48; CAPE, 1.53; EGF,
      1.90; control, 4.01. Production of OHP was significantly higher in controls.
      CONCLUSIONS: The results of the parameters in the study indicate that
      administration of CAPE and EGF has beneficial effects in the prevention of
      caustic esophageal strictures. Those effects of CAPE may occur through its
      antiinflammatory, immunomodulatory, and antioxidant properties, and EGF may occur
      through its induced proliferative properties on the esophagus.

PMID- 11584398
TI  - Specialty versus generalist care of children with appendicitis: an outcome
      comparison.
AB  - BACKGROUND/PURPOSE: Some Health Maintenance Organizations (HMO) limit access of
      their members to specialists to lower costs. The purpose of this study is to
      determine whether this policy affects the outcome of children with appendicitis.
      METHODS: At a large academic medical center, children 17 years or younger with
      appendicitis were treated either by an HMO Adult General Surgical Service (group
      A) or a Pediatric Surgical Service (group B). Board certified pediatric surgeons
      were not available on the HMO surgical service. Anesthesia, surgical residents,
      nursing, and ancillary support services were identical in both groups. Study
      parameters included imaging tests performed, operation type, complications,
      readmissions, and length of stay. Results were analyzed using chi(2) and
      Fischer's Exact tests. RESULTS: One-hundred seventy-five consecutive children
      underwent appendectomy, 96 in group A and 79 in group B. In patients with simple
      acute appendicitis, there was no significant difference between group A and group
      B for complications, readmissions, second operation, or length of stay. In
      patients with gangrenous or perforated appendicitis there was a significant
      difference between group A and group B for type of operation (laparoscopic
      appendectomy, group A, 4 of 27 v. group B, 0 of 34; P =.04); complications (group
      A, 9 of 27 v. group B, 3 of 34; P =.025); readmissions (group A, 6 of 27 v. group
      B, 0 of 34; P =.001); second operation (group A, 6 of 27 v. group B, 2 of 34; P
      =.001); and mean total length of stay in days (group A, 8.6 of 27 v. group B, 5.4
      of 34; P =.05). CONCLUSIONS: Children with significantly perforated appendicitis
      have lower complication rates and shorter lengths of hospital stay when treated
      by pediatric surgeons as compared with HMO adult general surgeons.

PMID- 11584399
TI  - Diversion procto-colitis: response to treatment with short-chain fatty acids.
AB  - BACKGROUND/PURPOSE: Diversion procto-colitis (DPC) results from a deficiency of
      luminal short-chain fatty acids (SCFAs). Endoscopic and histopathologic features
      of the disorder are almost universally present in defunctioned bowel, but
      symptomatic DPC is less common. METHODS: Five children with symptomatic DPC
      underwent endoscopy and rectosigmoid biopsies. An endoscopic index (EI) was used
      to quantify disease severity. An SCFA mixture was administered into the
      defunctioned bowel. RESULTS: A good clinical response and improvement in the
      endoscopic index occurred in all children. Undiversion or rectal excision was
      carried out in 4 and was curative in each case. One child is awaiting a redo pull
      through. CONCLUSIONS: DPC should be considered in children with a defunctioned
      colon presenting with evidence of colitis. Histopathology provides supportive
      evidence and SCFAs may provide effective relief of symptoms. Stoma reversal or
      rectal excision is curative.

PMID- 11584400
TI  - Cholecystectomy versus cholecystolithotomy for cholelithiasis in childhood: long
      term outcome.
AB  - BACKGROUND/PURPOSE: The presence of cholelithiasis is being reported with
      increased frequency in childhood. Little is known about the natural history of
      the disease, and only a few studies have been published regarding long-term
      results of treated patients. Controversy still exists regarding optimal
      treatment. Both cholecystectomy and cholecystolithotomy with gallbladder
      preservation have been recommended as the preferred operative intervention. The
      purpose of this study was to compare the long-term outcome of cholecystectomy
      versus cholecystolithotomy for symptomatic gallbladder disease in children.
      METHODS: The charts of all patients with symptomatic cholelithiasis treated in
      the Dublin Paediatric Hospitals during a 25-year period from 1974 till 1999 were
      reviewed. Data obtained included age, sex, age at presentation of symptoms,
      methods of diagnosis, indications for operative treatment, time interval between
      presentation of symptoms and surgery, surgical technique, performance of a
      preoperative or intraoperative cholangiogram, stone biochemistry, gallbladder
      histology, radiologic follow-up, the presence of recurrent or residual stones and
      symptoms, and the need for reoperation. Patient data were grouped according to
      method of surgery. All parameters were compared and evaluated. Follow-up was by
      way of telephone contact with all patients and completion of a questionnaire.
      RESULTS: There were 18 patients over a 25-year period. Eight patients underwent
      cholecystectomy, and 10 patients had a cholecystolithotomy. Median follow-up was
      2 years in the cholecystectomy group and 5 years in the cholecystolithotomy
      group. All patients in the cholecystectomy group are asymptomatic and have no
      recurrent or residual stones on follow-up ultrasound scan. Thirty percent of the
      patients in the cholecystolithotomy group have recurrent right upper quadrant
      pain, and 30% show recurrent stones 9.5 months (range, 7 to 12 months)
      postoperatively. One patient underwent cholecystectomy 8.5 months
      postcholecystolithotomy. CONCLUSIONS: The symptomatic high stone recurrence rate
      postcholecystolithotomy seen in our series suggest that cholecystectomy is the
      preferred treatment in patients with symptomatic gallbladder disease.

PMID- 11584401
TI  - 111 renal neoplasms of childhood: a clinicopathologic study.
AB  - PURPOSE: The aim of this study was to perform a clinicopathologic evaluation of a
      single pediatric institution renal tumor series. Most patients were treated
      within the frame of 3 consecutive SIOP trials, which included preoperative
      chemotherapy as their main feature. METHODS: Medical records and diagnoses of 111
      patients were reviewed. The association of pathologic features with outcome was
      investigated by means of the Kaplan-Meier method, the Cox model, and a logistic
      multivariate analysis. Comparison among different trial results was carried out.
      RESULTS: In 98 patients (88%), nephroblastoma was diagnosed, followed by 6 adult
      type renal tumors, 3 cystic nephromas, 2 mesoblastic nephromas, and 2 clear cell
      sarcomas. For nephroblastoma, a statistically significant correlation between
      grade and both disease-free survival rate and 5-year survival rate, and between
      stage and overall survival rate was shown. Lymph node involvement, local relapse,
      nephrogenic rests, and older age at presentation appeared to be less important
      prognostic factors. Tumor spillage was very sensitive to chemo or radiotherapy.
      No significant difference in outcome was observed among different trials.
      CONCLUSIONS: Wilms' tumor was the most frequent neoplasm and resulted in a 5-year
      cure rate of 90%. Clinical course was influenced mainly by diffuse anaplasia and,
      to a minor extent, by lymph node involvement. Because some tumors followed an
      unpredictable course, it is likely that also other biological factors played a
      significant role.

PMID- 11584402
TI  - Injuries from falls in the pediatric population: an analysis of 729 cases.
AB  - BACKGROUND/PURPOSE: Falls are classified as low or high level for triage
      purposes. Because triage criteria dictate less urgency for low-level falls, this
      classification scheme has important implications for pediatric emergency care.
      METHODS: Retrospective analysis was conducted of 729 (393 low-level and 336 high
      level) pediatric patients treated for fall-related trauma (1992 through 1998).
      Falls were classified as low (<15 feet) or high-level (> or =15 feet). All falls
      were reported as accidental or unintentional. RESULTS: The overall mortality rate
      was 1.6% (2.4% for high-level falls compared with 1.0% for low-level falls). All
      4 patients who died of a low-level fall had an abnormal head computed tomography
      (CT) scan and intracranial hypertension. Half of deaths from high-level falls
      were attributable to intracranial injuries, and half were caused by severe
      extracranial injuries. Common extracranial injuries were upper extremity fracture
      (6.2%), lower extremity fracture (5.6%), pulmonary contusion (1.8%), pneumothorax
      (1.1%), liver laceration (1.1%), bowel injury (1.0%), and splenic injury (2.1%).
      Orthopedic and thoracic injuries resulted more commonly from high-level falls,
      whereas abdominal injuries were as likely to occur after a low-level fall.
      CONCLUSIONS: Intracranial injury accounts for the majority of deaths from falls.
      Children suffering low-level falls were at similar risk for intracranial and
      abdominal injuries compared with those who fell from greater heights. Pediatric
      trauma triage criteria should account for these findings.

PMID- 11584403
TI  - Latex allergy in pediatric surgery is dependent on repeated operations in the
      first year of life.
AB  - BACKGROUND/PURPOSE: Patients with spina bifida represent the highest risk group
      for hypersensitivity to latex. Recognized risk factors for these patients are
      repeated surgery and an atopic disposition. Little is known about children
      operated on in the first year of life for reasons other than spina bifida.
      METHODS: Eighty-six patients (mean age, 10.2 years) with gastrointestinal or
      urologic surgery were investigated for the number, type, and date of surgical
      interventions. Additionally, skin prick tests and provocation tests were
      performed to classify sensitized and symptomatic latex-allergic individuals.
      RESULTS: Twenty-seven patients were regarded as sensitized to latex (31.4%).
      Twenty patients were classified as being atopic (25.6%). Atopic patients were
      significantly more often sensitized and provocation positive compared with
      nonsensitized and provocation-negative ones (P <.01). Children already operated
      on in the first year of life (n = 44) with a positive provocation showed
      significantly higher latex-specific IgE-values than individuals with a negative
      outcome (P <.0001). The total number of operations and degree of sensitization
      showed a significant correlation; more than 8 surgical interventions during the
      first year of life significantly increased the risk of clinically relevant
      allergy to latex. CONCLUSION: This study emphasizes that individuals undergoing
      surgical interventions during infancy should be handled latex free from the very
      beginning of life.

PMID- 11584404
TI  - Gastroschisis minor.
AB  - BACKGROUND: Since 1994 the author has seen a number of cases of what appear to be
      a minor variant of gastroschisis. METHODS: The case files of all neonates with
      gastroschisis (GS) presenting to the neonatal ward of the Queen Elizabeth Central
      Hospital (QECH), a referral hospital in Blantyre, Malawi, from January 1995 to
      December 1998 were reviewed and the presentation and survival noted. RESULTS:
      Twenty-one neonates were seen; only 2 of 15 with "normal" GS survived. The other
      patients had gastroschisis minor (GSM) and all left the hospital alive.
      CONCLUSION: In the context of the constraints and difficulties encountered in the
      treatment of gastroschisis in a developing country, this subgroup of patients
      with a more minor form of gastroschisis shows a distinct survival advantage.

PMID- 11584406
TI  - Adolescent varicocele: treatment by antegrade sclerotherapy.
AB  - BACKGROUND/PURPOSE: The most effective treatment for adolescent varicocele is
      still debated, although the same treatment methods used for adults have also been
      used in children. Since 1991 at the Pediatric Surgery Operative Unit of "S.
      Camillo" Hospital in Rome a multidisciplinary protocol has been established
      according to which percutaneous retrograde scleroembolization was suggested as
      the first therapeutic option. Surgery (retroperitoneal ligation) was reserved for
      select cases. The author now presents his personal experience with alternative
      approach antegrade sclerotherapy. METHODS: Since February 1998, as an alternative
      to percutaneous retrograde sclerosis and surgical ligation, antegrade
      sclerotherapy has been performed in 92 varicocele patients, 65 of whom were 11 to
      19 years of age. In this group, the indication for treatment was grade III
      varicocele with spontaneous continual reflux, which worsened with the Valsalva
      maneuver. Twenty patients had recurrent varicocele after other treatments.
      RESULTS: At a mean follow-up of 9 months, the clinical recovery rate was 92.6%.
      CONCLUSIONS: Antegrade sclerotherapy is an intermediate treatment because of its
      invasive nature and success rate compared with more commonly used percutaneous
      retrograde sclerosis and Palomo procedures in adolescents. In particular, this
      method is highly effective and well-accepted by patients with recurrent
      varicocele.

PMID- 11584405
TI  - Management of intestinal atresia in patients with gastroschisis.
AB  - BACKGROUND/PURPOSE: Intestinal atresia occurs in approximately 10% to 20% of
      children with gastroschisis and may be missed at the initial closure if a thick
      peel obscures the bowel. Some investigators have identified intestinal atresia as
      a significant contributor to morbidity and mortality. The authors reviewed their
      experience with gastroschisis and intestinal atresia in an attempt to answer the
      following questions. What is the incidence of this association? How often is the
      intestinal atresia unrecognized as a result of the peel? What is the optimal
      management for infants with atresia and gastroschisis, and does the atresia
      affect morbidity or mortality? METHODS: The hospital charts and medical records
      of all patients with gastroschisis treated at our institution from 1969 to
      present were reviewed thoroughly. Parameters analyzed included gestational age
      (GA), birth weight (BW), antenatal diagnosis, mode of delivery, type of closure,
      era of repair, presence of other major anomalies, and development of necrotizing
      enterocolitis. Morbidity and mortality rates were examined. Characteristics of
      patients with and without atresia were compared. Chi-squared was used for
      crosstabular analysis. Sample parameters were compared with Student's t test. P
      values of less than.05 were considered significant. RESULTS: A total of 199
      babies had gastroschisis and 25 (12.6%) had intestinal atresia. Intestinal
      atresia was initially unrecognized in 3 patients. Most patients (80%) underwent
      primary closure of the abdominal wall. Initial stoma formation and delayed
      anastomosis was performed in 12 (48%) patients, none of whom required prosthetic
      material for abdominal wall closure. Initial stomas were avoided in 5 patients
      who required SILASTIC (Dow Corning, Midland, MI) silos. Skin closure alone was
      used in 2 babies. The level of the atresia was most commonly jejunoileal (20 of
      25, 80%). Mean hospital stay was increased in babies with intestinal atresia,
      36.2 versus 63.1 days (P <.001). CONCLUSIONS: Although patients with intestinal
      atresia did have feeding delays, an increased incidence of adhesive intestinal
      obstruction, and prolonged hospitalization, neither chi(2) nor logistic
      regression analysis showed any correlation with mortality. Intestinal repair at
      the first operation is sometimes possible and depends on the severity of the
      peel. Delayed repair of the atresia after a period of bowel decompression and
      parenteral nutrition is preferred, but in certain situations (colonic atresia,
      necrotic intestine, complicated atresia) may not be possible. The combination of
      stomas and prosthetic material can be avoided in almost all patients. A
      management algorithm for patients with atresia and gastroschisis is discussed.

PMID- 11584407
TI  - Mechanisms involved in contractile differences among cremaster muscles according
      to localization of testis.
AB  - BACKGROUND/PURPOSE: Evidence suggests differences in contractility in cremaster
      muscles (CM) associated with undescended testis caused by alterations of
      autonomic innervation. Contractile responses of CM to various pharmacologic
      agents were evaluated and compared according to the localization of testis.
      METHODS: Samples of CM from boys with undescended testis or inguinal hernia were
      obtained. Twitch and tetanic contractions were recorded isometrically at 37
      degrees C. Effects of verapamil, isoprenaline, calcitonin gene-related peptide
      (CGRP), substance P (SP) and N(omega)-nitro-L-arginine (L-NNA) were investigated.
      Results were compared through 2-way analysis of variance, and P values less
      than.05 were considered to be different. RESULTS: Verapamil alone significantly
      (P <.05) decreased contraction amplitudes in CM from both sources; the decrease
      was more pronounced in CM from boys with inguinal hernia (P <.05). Although
      isoprenaline increased contraction amplitudes in CM associated with undescended
      testis (P <.05), CGRP and SP increased contraction amplitudes in CM associated
      with descended testis (P <.05). L-NNA increased contraction amplitudes in both
      groups (P <.05). The decrease of contraction amplitudes after verapamil displayed
      a similar pattern after isoprenaline, SP, and L-NNA. Verapamil-induced
      contractility decrease was more pronounced after CGRP in both groups (P <.05).
      CONCLUSIONS: Sensitivity of CM to verapamil differs according to localization of
      testis. Isoprenaline enhances contractility by stimulating Na(+)-K(+)ATPase in
      undescended testis without altering voltage-sensitive channel sensitivity to
      verapamil. CGRP and SP increase contractility in inguinal hernia, and CGRP
      increases the sensitivity of voltage-sensitive Ca(2+) channels to verapamil in CM
      from both groups. Nitric Oxide (NO) exerts inhibitory action on CM contractility,
      and it is less pronounced in undescended testis. These differences may contribute
      to pathophysiology of undescended testis.

PMID- 11584408
TI  - Incidence of contralateral patent processus vaginalis in children with inguinal
      hernia.
AB  - PURPOSE: The aim of this study was to investigate the incidence of contralateral
      patent processus vaginalis (PPV) in children with inguinal hernia using direct
      laparoscopic inspection. METHODS: This study evaluates the incidence and size of
      contralateral PPVs in 143 children (96 boys, 47 girls) with clinically unilateral
      indirect inguinal hernia who underwent laparoscopic hernia repair. During repair,
      the contralateral internal inguinal ring was evaluated for PPV. RESULTS: Boys
      with hernias on the right side had wide-open contralateral PPVs in 26% of cases
      compared with 11% in girls. Boys with hernias on the left side had wide-open
      contralateral PPVs in 30% of cases compared with 38% in girls. In all 4 groups,
      there were small contralateral openings in 15% to 20% of cases. CONCLUSION:
      Contralateral PPV seems to occur less commonly than previously assumed.

PMID- 11584409
TI  - Laparoscopic Nissen fundoplication with carbon dioxide pneumoperitoneum preserves
      cell-mediated immunity in an immature animal model.
AB  - PURPOSE: The aim of this study is to elucidate the effects of laparoscopic Nissen
      fundoplication (LNF) with carbon dioxide (CO(2)) or helium (He) on the cell
      mediated immune response in a pediatric animal model compared with open Nissen
      fundoplication (ONF). METHODS: Cell immune response was evaluated in 45 1-week
      old Sprague Dawley rats using the delayed type hypersensitivity (DTH) skin test.
      Animals were sensitized against keyhole limpet hemocyanin (KLH) by subcutaneous
      injection (0.5 mg) in complete Freund's adjuvant. Animals were challenged 2 weeks
      later by an intradermal injection of KLH (0.3 mg) in sterile saline (challenge 1,
      baseline). Rats with positive DTH skin reaction at 24 and 48 hours after
      challenge 1 were put randomly into 4 groups (n = 10 each): I, only anesthesia
      (control); II, LNF with CO(2), III, LNF with He; IV, ONF. Animals were injected
      intradermally with KLH (0.3 mg) immediately before the procedures (challenge 2)
      and 3 and 6 days postoperatively (challenges 3 and 4). RESULTS: DTH skin
      reactions were measured 24 and 48 hours after each challenge. There were no
      significant changes in cell-mediated immunosuppression after LNF with CO(2).
      However, a transient cell-mediated immunosuppression was observed after LNF with
      He and ONF. All fundoplications were intact at the time of necropsy. CONCLUSIONS:
      These data suggest a transient suppression of cell-mediated immunity in open
      procedures when compared with laparoscopic interventions using CO(2) in a
      pediatric animal model. In addition, the type of gas used during laparoscopy also
      may modulate this transient immunosuppression.

PMID- 11584410
TI  - Impaired esophageal reactivity in adriamycin-induced rat esophageal atresia: an
      in vitro study.
AB  - PURPOSE: The aim of this study was to investigate the reactivity of lower
      esophageal smooth muscle in the Adriamycin-induced esophageal atresia (EA) rat
      model. METHODS: The fetuses were divided into 3 groups. The control group was
      exposed to saline. The second group comprised fetuses that were exposed to
      Adriamycin but in whom EA did not develop. The third group comprised of fetuses
      that were exposed to Adriamycin and EA was observed. The reactivity of distal
      esophageal strips was studied in organ chambers. RESULTS: The tension was similar
      in all groups precontracted with carbachol for the study of relaxation to
      serotonin. Relaxation of lower esophageal strips to serotonin was comparably
      unaffected in the control and Adriamycin-no EA groups, whereas it was
      significantly inhibited in the EA group with decreased E(max) and pD(2) values.
      Contractile responses of esophageal smooth muscle to carbachol or 80 mmol/L KCl
      and relaxant responses to papaverine were similar in all groups. No change in
      agonist potency was observed among the groups. CONCLUSIONS: Our study showed
      impairment of serotonin-receptor-mediated relaxation; but not of cholinoceptor
      mediated contraction of the lower esophageal smooth muscle in the EA. Thus,
      impaired relaxant responses may be, at least in part, a contributing factor in
      the esophageal dismotility seen in EA.

PMID- 11584411
TI  - Pylephlebitis after appendicitis in a child.
AB  - Septic phlebitis of the portal vein, or pylephlebitis, is a rare but potentially
      severe complication of abdominal sepsis. The authors present a case of
      pylephlebitis after perforated retrocecal appendicitis in a child and discuss the
      etiology, presentation, diagnosis, and treatment of this disorder in the modern
      era.

PMID- 11584412
TI  - Disseminated actinomycosis presenting as a renal tumor with metastases.
AB  - Disseminated actinomycosis is uncommon in the pediatric population and rarely
      presents as a renal mass mimicking a renal tumor with metastases. Diagnosis may
      be difficult. In this case, percutaneous biopsy results only showed necrosis and
      fibrosis and, hence, were not helpful in diagnosis. Exploratory laparotomy and
      open biopsy results showed that this renal tumor was an actinomycotic abscess
      with similar abscesses in the liver and lung masquerading as metastases. The
      treatment for disseminated actinomycosis is with parenteral and oral penicillin.

PMID- 11584413
TI  - An unusual presentation of appendicitis: vaginal discharge.
AB  - An unusual complication of appendicitis, perforation of pelvic appendicitis into
      the uterinal cavity in a 3-year-old girl, is presented in this report.

PMID- 11584414
TI  - Cecal duplication causing a disappearing abdominal mass in an infant.
AB  - Duplications of the alimentary tract are rare malformations. A case of a 2-year
      old girl with an intestinal intussusception caused by a cystic duplication of the
      cecum is presented. This case report is justified by its clinical features and
      the difficult diagnosis, which was only confirmed during surgery. Ultrasonography
      had documented an abdominal mass that then disappeared and later reappeared,
      leading to surgical indication. During surgery, the intussusception within the
      abdomen was reduced, and right hemicolectomy was performed around the mass in the
      interior part of the cecum and appendix, with ileocolic anastomosis. On resecting
      the cecum, a cystic duplication measuring 4 x 3 cm was observed, with a granular
      mucous layer, an ulcerated hole in its interior, and inflammatory reaction. The
      patient had an uneventful recovery and was discharged on the fourth postoperative
      day.

PMID- 11584415
TI  - Primary papillary hyperplasia of the gallbladder: a rare cause of biliary colic.
AB  - Primary papillary hyperplasia of the gallbladder is a rare, poorly defined,
      clinicopathologic entity in adults. The authors describe a 12-year-old girl with
      this finding in the neck and body of the gallbladder. She presented with biliary
      colic, and ultrasonography of the gallbladder showed persistent thickening of the
      gallbladder wall but no evidence of calculi. Her symptoms resolved completely
      after cholecystectomy.

PMID- 11584416
TI  - Infantile digital fibromatosis: an unusual localization.
AB  - Infantile digital fibromatosis (recurrent digital fibromatosis) is a rare, benign
      fibrous growth of childhood. The authors present a case of a 16-year-old child
      with an infantile digital fibromatosis on the volar surface of the right little
      finger at the distal interphalangeal joint level. After excision of the tumor,
      histopathologic diagnosis was shown to be infantile digital fibromatosis. The
      patient has been free of recurrence for 3 years after surgery.

PMID- 11584417
TI  - Severe hypothermia with cardiac arrest: complete neurologic recovery in a 4-year
      old child.
AB  - A 4-year-old girl was lost for 17 hours in a snowstorm. Upon discovery, her core
      temperature was 72 degrees F (22 degrees C). While undergoing endotracheal
      intubation in the emergency department, she experienced sudden ventricular
      fibrillation and cardiac arrest. Closed chest cardiopulmonary resuscitation (CPR)
      was instituted, and standard rewarming measures were begun. Despite this, neither
      core temperature, nor the patient's arrhythmia, changed. An infraumbilical "mini
      laparotomy" incision was made, with placement of a large silicone peritoneal
      dialysis catheter into the abdomen. This was then connected to a rapid infuser
      device, with the delivery of 1L of warmed, normal saline every 90 seconds. The
      core temperature reached 29 degrees C in 15 minutes, and a palpable pulse was
      detected. Lavage was continued until core temperature reached 34 degrees C, at
      which time transport to the pediatric intensive care unit was arranged. She was
      extubated the next day and discharged home, on the fourth hospital day, with
      apparent complete neurologic recovery. This is the first report of the successful
      use of rapid high-volume peritoneal lavage for the treatment of accidental severe
      hypothermia in a pediatric patient.

PMID- 11584418
TI  - Congenital pouch colon associated with segmental dilatation of the colon.
AB  - A 1-day-old boy who presented with an anorectal malformation (ARM) was found to
      have a segmental dilatation of the colon (SDC) associated with a typical
      congenital pouch colon (CPC) malformation. The distal colonic pouch terminated in
      a high colovesical fistula. The posterior portion of the perineal raphe was
      duplicated and ended in 2 anal dimples. Both dilated segments of the colon were
      excised. The similarity between CPC and SDC is highlighted, and the possible
      embryogenesis of both conditions is discussed.

PMID- 11584419
TI  - Infantile lobar emphysema and tracheal bronchus in a patient with congenital
      heart disease.
AB  - A 7-month-old girl was admitted with severe respiratory distress. Chest
      roentgenogram showed hyperinflation of the right middle lobe and mediastinal
      shift. Bronchogram showed tracheal lobe displaced superiorly by the hyperinflated
      right middle lobe. Echocardiography showed left-to-right shunt at the ventricular
      level. The patient responded well after surgical correction of cardiac defect.
      Four years after the operation, computed tomography examinations showed no
      evidence of emphysema.

PMID- 11584420
TI  - Hepatocellular carcinoma with lung metastasis in a 9-year-old-boy.
AB  - Hepatocellular carcinoma (HCC) remains chemoresistant and, therefore, the
      principal treatment of HCC is surgical resection. After a 9-year-old boy with
      huge HCC with lung metastasis received the 5 cycles of chemotherapy (cisplatin
      and Adriamycin), the lung metastasis had been resolved completely and the size of
      HCC in liver had decreased. Right hepatic trisegmentectomy was performed, and
      then the additional 3 cycles of chemotherapy was given. Currently, the patient
      shows no recurrence of HCC 42 months after surgical extirpation.

PMID- 11584421
TI  - Pediatric extragonadal germ cell tumor of the scalp.
AB  - Extragonadal germ cell tumors are relatively rare tumors, accounting for 5% to
      10% of all germ cell tumors in adults. In children, approximately two thirds of
      germ cell tumors are extragonadal. Extragonadal germ cell tumor of the scalp is
      exceedingly rare. The authors report the case of a 1(1/2)-year-old boy with
      extragonadal germ cell tumor over the occipital region. Examination of the chest,
      abdomen, and gonads was normal. Computed tomography scan of the head showed a
      large, well-defined, lobulated, heterogeneously enhancing soft tissue mass lesion
      in the occipital region. The underlying bone was normal with no evidence of
      intracranial extension. Biopsy results of the scalp mass showed features
      consistent with embroynal carcinoma. Serum alpha-fetoprotein (AFP) level was
      elevated. The child was started on chemotherapy and received 4 cycles of
      cisplatin, etoposide, and bleomycin (PEB). There was more than 90% reduction in
      the size of the mass at the end of the fourth cycle. The residual mass was
      excised and followed up with 2 cycles of postoperative PEB. Ten months after
      excision the patient is well, without recurrence, and the AFP level is normal.

PMID- 11584422
TI  - A historical vignette, the Halifax disaster of 1917 and the birth of North
      American Pediatric Surgery.

PMID- 11584423
TI  - Aplasia of the right lung in a 4-year-old child: surgical stabilization of the
      mediastinum by diaphragm translocation.

PMID- 11584425
TI  - Collision tumor in children: a review of the literature and presentation of a
      rare case of mesoblastic nephroma and neuroblastoma in an infant.

PMID- 11584429
TI  - Physical functioning and health-related quality of life: before and after total
      hip replacement.
AB  - Total hip replacement (THR) is a commonly adopted procedure for arthritis-related
      diseases. Although the THR efficacy in pain relief and restoration of physical
      functioning has been extensively studied, it remains unclear how health-related
      quality of life is affected by THR. The major purpose of this study was to
      examine and compare the differences in physical functioning and health-related
      quality of life for THR patients before and after operations. Based on a
      prospective study design, 46 THR patients at one medical center were reviewed and
      followed up (six months after operations) during the period from March 1997 to
      June 1998, with a follow-up rate of 88%. The THR subjects were interviewed and
      measured by the Modified Harris Hip Scale and the Chinese-version Short-form 36
      item Health Survey (SF-36). Patient characteristics and the information related
      to procedures were derived from chart review. The results indicated that the THR
      patients had statistically significant improvements in physical functioning and
      health-related quality of life. In terms of the Harris Score, the mean Harris
      score was 91.6 (SD = 10.7) 6 months after THR, as compared to 45.2 (SD = 17.3)
      before THR. The eight ratings in the SF-36 measures were also statistically
      significantly improved (p < 0.001). Specifically, "role limitations due to
      physical functioning" demonstrated dramatic improvements after THR (15.2 vs.
      63.5), followed by "role limitations due to emotional problems" (25.4 vs. 85.5).
      The findings confirm the effectiveness of THR outcomes in terms of physical
      functioning, pain relief, and health-related quality of life, which can be
      revealed by disease-specific (Harris Scale) and generic health measures (SF-36).

PMID- 11584428
TI  - Clinical significance of distribution patterns of P53 immunoreactivity in
      astrocytic tumors.
AB  - The difference of prognosis in patients with the same WHO grade of astrocytic
      tumors suggests that such tumors comprise a heterogeneous group in biological
      behavior. The correlation between p53 immunoreactivity and prognosis has often
      been reported but remains controversial. From the perspective of clonal expansion
      of p53 immunopositive cells, the distribution patterns of p53 immunoreactivity
      can be divided into four types: negative, scattered, focally clustered, and
      diffusely clustered. The survival rate was evaluated by classifying the p53
      immunoreactivity into two groups: the significantly immunopositive patterns
      (focally and diffusely clustered types) and the significantly immunonegative
      patterns (negative and scattered types). The survival analysis showed a highly
      significant difference between these two patterns within the same WHO grade of
      astrocytic tumors (p = 0.0185). Our studies demonstrate that the distribution
      patterns of p53 immunoreactivity, which reflect the trends of clonal expansion of
      p53 immunopositive cells, are significantly valuable in predicting the prognosis
      of patients with the same WHO grade of astrocytic tumors.

PMID- 11584430
TI  - Comparison of appendectomy medical expense and clinical outcome between fee for
      service and prospective payment system.
AB  - Since the introduction of national health insurance on March 1st 1995 in Taiwan,
      another 9 items (including appendectomy) were introduced into the
      Taiwan/prospective payment system (T/PPS). The modified T/PPS was based on those
      complicated appendectomy cases with secondary diagnosis or second operation where
      a total fee over 37,500 New Taiwan (NT) dollars was paid by National Health
      Insurance Bureau (NHIB) according to the real cost. The T/PPS was implemented in
      October 1997 due to the continuously increasing financial burden of medical
      expenses on the NHIB. The purpose of this study is (1) to compare the length of
      stay (LOS) and total medical expense of appendectomy of fee for service (FFS) and
      T/PPS and (2) to compare the clinical outcome of wound healing after discharge of
      the two systems by telephone interview. Our study investigated 100 consecutive
      appendectomy cases under FFS payment system and 99 consecutive appendectomy cases
      under T/PPS. We retrospectively analyzed LOS, operation time, and hospital cost
      of different items through chart review and computer data. Our results revealed
      that the LOS and operation time of T/PPS were significantly shorter than those of
      FFS (both p < 0.01). The total hospital cost, fee for room service, treatment,
      pharmacy, examination and anesthesia in T/PPS were also significantly less than
      those in FFS (all p < 0.01, except for anesthesia p < 0.05). There existed
      positive correlation between total hospital cost and LOS, operation time, fee for
      room service, treatment, pharmacy, examination and anesthesia both for T/PPS and
      FFS. To evaluate the clinical outcome of appendectomy between T/PPS and FFS, we
      interviewed 73 T/PPS cases and 73 FFS cases by telephone and chart review. Our
      results revealed that there were no significant differences in frequencies of
      having painful incision, clear incision wound on the day of discharge, and
      removal of stitches at hospital (p all > 0.05). We concluded that compared to
      FFS, T/PPS can decrease LOS and total hospital cost of appendectomy, and T/PPS's
      clinical outcome of appendectomy in T/PPS showed no significant difference from
      that in FFS.

PMID- 11584431
TI  - Crown diameters of the deciduous teeth of Taiwanese.
AB  - The purposes of this study were (1) to characterize the crown diameters of the
      deciduous teeth of Taiwanese; (2) to compare the differences in the deciduous
      crown diameters between different populations. The results might provide
      odontometric information in making preformed stainless steel crowns of the
      Chinese population. Study casts of 90 children (51 boys and 39 girls) of aged 3
      to 6 years were used in this study. The maximum mesiodistal crown diameter (the
      greatest distance between the contact points of the approximal surfaces) and the
      buccolingual crown diameter (the greatest distance at a right angle to the
      mesiodistal measurement) were obtained by using an electronic digital caliper.
      Significant differences between antimeres were found in the mesiodistal diameters
      of maxillary canine and maxillary molars (p < 0.001) as well as in the
      buccolingual diameters of mandibular molars (p < 0.05). Excellent correlations
      between the antimeres of the corresponding teeth were found (r = 0.70 to 0.96).
      Boys generally had larger crown diameters than girls with the exception of
      mesiodistal diameters of maxillary and mandibular canines, and mandibular lateral
      incisor, whereas the statistically significant gender difference was only found
      in the buccolingual diameter of mandibular second molar (p < 0.05). The higher
      the percentage of sexual dimorphism, the larger the gender differences. The
      percentage of sexual dimorphism ranged from 0.09 to 1.94 for mesiodistal
      diameters and 0.04 to 2.86 for buccolingual diameters. The mandibular second
      molar was the most dimorphic tooth. Variations in the crown diameters of the
      deciduous teeth existed among and within different populations. Deciduous
      mesiodistal crown diameters of Taiwanese were, in general, smaller than those of
      Australian aborigines, Taiwan Chinese aborigines, and Hong Kong Chinese, but
      larger than those of American whites. When considering the buccolingual crown
      diameters, our data were significantly smaller than those of Icelanders, western
      Indians, and whites.

PMID- 11584432
TI  - The mental health in mothers with autistic children: a case-control study in
      southern Taiwan.
AB  - The aim of this study was to investigate the impact of autistic children on the
      mental health of their mothers. Autism is a complicated neuropsychiatric
      disorder. Evidence shows that mothers with autistic children experience greater
      stress than those having children with other chronic diseases. In this study we
      have 1) assessed the mental health of mothers with autistic children; 2)
      determined their prevalence of minor psychiatric morbidity (MPM); 3) classified
      their MPM; and 4) determined factors related to their mental health. A case
      controlled design was used to compare the mental status among mothers having
      children with either autistic (n = 30), or Down syndrome (n = 11) and with normal
      children (n = 56). The mean score of the Chinese Health Questionnaire (CHQ)
      showed no differences between those mothers of case and control groups. Using a 9
      point criterion to screen for MPM in the CHQ, more mothers (37%) in the case
      group had scores > or = 9 compared with the control group (18%). Mothers of the
      case group had significantly higher for MPM using logistic regression analysis.
      The educational level was inversely related to the CHQ scores. Mothers with a CHQ
      score > or = 9, were later diagnosed with either depression (36%) and anxiety
      (46%); or anxiety and depression (9%). A primary care model for mothers with
      autistic children should therefore be developed to prevent them from developing
      mental disorders.

PMID- 11584433
TI  - Multiple skeletal metastases of Ewing's sarcoma demonstrated on FDG-PET and
      compared with bone and gallium scans.
AB  - Bone and gallium scans have been shown to be useful in imaging Ewing's sarcoma.
      Here we report on a case of recurrent Ewing's sarcoma with multiple skeletal
      metastases demonstrated by the FDG-PET whole body scan, while the bone scan
      revealed fewer lesions and a non-remarkable finding was found on the gallium
      scan. The following pathologic examination showed bone marrow involvement. This
      case demonstrated that the FDG-PET could detect more lesions of metastatic
      Ewing's sarcoma than bone and gallium scans, especially for those with bone
      marrow involvement.

PMID- 11584434
TI  - Tc99m sulfur colloid scintigraphy for detection of intrathoracic extramedullary
      hematopoiesis in patient with beta-thalassemia major--a case report.
AB  - Extramedullary hematopoiesis (EMH) refers to the production of blood cells
      outside the bone marrow and is a compensatory mechanism for bone marrow
      dysfunction. A 34 year-old female patient with beta thalassemia major was found
      to have multiple large, well-circumscribed radiopaque paravertibral mass lesions
      in chest radiography. Magnetic resonance imaging (MRI) of the thorax disclosed a
      right upper apical and two lower thoracic paraspinal mass lesions with
      heterogeneous isointensity on T1-weighted images and hypointensity on T2-weighted
      images. Because intrathoracic EMH is suspected in our case, which had obvious
      bone marrow dysfunction, radionuclide bone marrow scintigraphy is helpful in
      supporting the diagnosis. Tc99m sulfur colloid scintigraphy demonstrated three
      intense radioactive thoracic paraspinal mass lesions corresponding to the lesions
      seen on MRI. We believe whole body bone marrow scintigraphy with Tc99m sulfur
      colloid is the best convenient noninvasive method for supporting the diagnosis of
      EMH.

PMID- 11584435
TI  - Reversible axial myopia following infectious scleral ulceration--a case report.
AB  - Adult-onset axial myopia is uncommon in comparison with the lenticular myopia.
      When we dealt with a case of the infectious scleral ulceration, the progressive
      myopic shift was not only due to the dense nuclear sclerosis but also due to the
      longer axial length. The elongating axis became shortened after 3-months follow
      up. Then the patient underwent uneventful cataract surgery. However, the reversal
      process persisted even after the operation. Although the pathogenesis is not well
      known, we concluded that the cataract surgery in dealt with the complicated
      cataract should be delayed in the cases with any inflammation or the axial
      changes.

PMID- 11584436
TI  - [Image of the month. Cerebral abscess and toxoplasmosis].

PMID- 11584437
TI  - [Clinical case of the month. Porto-pulmonary hypertension syndrome associated
      with severe hypoxemia].
AB  - We report the case of a patient with liver cirrhosis who was admitted to the
      emergency room for rapid occurrence of dyspnea and severe hypoxemia at rest. Lung
      CT-scan and echocardiography did not disclose any right-to-left shunt and right
      sided heart catheterization evidenced major precapillary pulmonary hypertension.
      The present feature supports the hypothesis that the pulmonary complications of
      cirrhosis, the hepatopulmonary syndrome and the portopulmonary hypertension,
      which are usually considered as mutually exclusive, may coexist. In such
      circumstances, the right failing heart is the major determinant to the immediate
      prognosis.

PMID- 11584438
TI  - [Clinical case of the month. Severe dyskinetic syndrome induced by ranitidine].
AB  - We report a case of severe dyskinetic syndrome, consisting of intense myoclonia
      movements, associated with choreiform activity involving the face and upper
      extremities. The abnormal movements occurred in a patient with confusion and
      visual hallucinations. This syndrome had an abrupt onset in a patient recovering
      from coronary artery bypass surgery complicated by an early post-operative
      cardiac arrest and acute renal failure. Dyskinesia appeared several days after
      intravenous administration of ranitidine for stress ulcer prophylaxis. Several
      etiologies were raised in this case among which were post-anoxic myoclonia and
      metabolic encephalopathy. Cessation of histamine receptor blocker therapy for 48
      hours was associated with return of normal cognitive function and disappearance
      of abnormal movements. This confirmed the iatrogenic nature of the syndrome
      related to administration of ranitidine.

PMID- 11584439
TI  - [How to integrate blood pressure self-monitoring in the management of the
      hypertensive patient].
AB  - Blood pressure measurement is the cornerstone of the diagnosis and follow up of
      arterial hypertension. Because of its large variability, the office blood
      pressure measurement can hardly be trusted. The blood pressure self measurement
      allows more precisely to select the hypertensive patients (BP > 135/85 mmHg), to
      follow with more accuracy patients with important blood pressure variability and
      to check the efficacy of antihypertensive treatment. The self blood pressure
      measurement is at the early stage of its scientific period of development but
      requires the use of strictly validated devices which only measure the blood
      pressure at the brachial level.

PMID- 11584440
TI  - [Update on pancreatic transplantation].
AB  - Pancreas transplantation significantly improves the quality of life as well as
      the survival of the diabetic patient. It is also associated with stabilization
      and reversal of secondary diabetic complications. Improvements in organ
      preservation, surgical techniques and immunosuppression have achieved one-year
      graft survival of more than 90% for combined kidney-pancreas transplant and 80%
      for isolated pancreas transplantation. Recipient evaluation must weigh the
      benefits of the procedure with the risk associated with surgery and chronic
      immunosuppression. Combined kidney-pancreas transplantation appears today as the
      best treatment for the diabetic patient with end stage renal disease. Isolated
      pancreas transplantation is reserved to non-uremic patients with severe diabetic
      complications or with brittle glycaemic control and severe impairment of quality
      of life.

PMID- 11584441
TI  - [Blood saving and surgery].
AB  - Blood-loss reduction strategies have numerous benefits for the patient. These
      include less transfusion reactions and decreased transmission of infections.
      Decreased requirements for bank blood mitigate the scarcity of this vital
      resource. The techniques for blood "savings" include lowering the transfusion
      trigger, stimulation of the marrow with erythropoietin, pre-donation,
      normovolemic hemodilution, and recovery of shed blood. Anesthetic and/or surgical
      techniques can be chosen to reduce bleeding, while various pharmacology agents
      can also reduce blood loss. Oxygentransporting artificial hemoglobin or
      perflurocarbon solutions can also reduce dependence on transfusion. Of the above
      techniques, the most promising are marrow stimulation, reductions of blood loss,
      and artificial oxygen transporters.

PMID- 11584442
TI  - [Mad cow disease and the new variant of Creutzfeldt-Jakob disease].
AB  - Bovine spongiform encephalopathy and the new variant of Creutzfeldt-Jakob disease
      (vCJD) belong to a family of similar diseases under the name of transmissible
      spongiform encephalopathies (TSE). It is demonstrated that the agent responsible
      for bovine spongiform encephalopathy (BSE) is also responsible for the new
      variant of Creutzfeldt-Jakob in man. This contribution describes the main
      characteristics of the two diseases.

PMID- 11584443
TI  - [Ultra-fast opiate detoxification under general anesthesia: preliminary results
      of the Liege protocol].
AB  - Many studies support the hypothesis of a substantial benefit in inducing an
      Opiate Receptor Blockade through a Rapid Opiate Detoxification under general
      Anaesthesia (RODA) in opiate dependent patients. However, prospective studies and
      long term evaluation of the technique are lacking. In order to evaluate long-term
      abstinence rates after a RODA among a sample of opiate addicts, a study was
      started in March 1999 at the University of Liege. To date, 45 patients were
      evaluated (mean age: 29 +/- 5 years) with a mean opiate dependence duration of 8
      +/- 4 years. Most of them were both heroin and methadone dependent; 42.2% of them
      were included while 31.1% did not complete the whole inclusion procedure and
      26.7% were excluded. None experienced severe withdrawal symptoms. At six months,
      abstinence rate was 67% and 46% at one year. These preliminary results suggest
      the interest of the procedure in carefully selected patients.

PMID- 11584444
TI  - [Finapres, efficient technique in the assessment of orthostatic hypotension,
      autonomic neuropathy, and vaso-vagal syncope].
AB  - Finapres is a device able to continuously and non invasively measure arterial
      blood pressure by photoplethysmography in the finger. It can be used in various
      dynamic tests which involve cardiocirculatory adjustments, as a passive posture
      test ("tilt test") or an active orthostatic test (from squatting to standing
      position in the so-called squatting test). It represents a valuable help in the
      diagnosis of orthostatic hypotension (of endogenous or iatrogenic origin), of
      autonomic neuropathy (secondary to diabetes mellitus or to a neurological
      disease) or of vasovagal syncope. All these conditions are characterized by a
      defect of arterial and venous vasoconstriction and by an insufficient reflex
      tachycardia because of autonomic dysfunction.

PMID- 11584445
TI  - [Drug-induced dermatoses, a ransom in the search for health].
AB  - Muco-cutaneous drug reactions are side effects secondary to the intake of various
      medications. They are quite frequent and diverse in their clinical presentation,
      pathogeny, histology and prognosis. It is important to diagnose and adequately
      monitor the disease in its early evolving phase.

PMID- 11584446
TI  - [Fatal rhabdomyolysis caused by cerivastatin].
AB  - Cerivastatin was recently withdrawn from the market after the report of more than
      30 deaths in the United-States among patients receiving a combination of
      cerivastatin and gemfibrozil, a fibrate which is not anymore on the Belgian
      market. The cause of death was attributed to severe rhabdomyolysis. Cases were
      also reported among patients treated by cerivastatin only. Recommendations for
      better use of lipid-lowering drugs are given in order to optimize the
      benefit/risk ratio of such treatment.

PMID- 11584447
TI  - [Shoshin beriberi: myth or reality?].

PMID- 11584448
TI  - Codon 129 polymorphism of the PRNP gene in normal Polish population and in
      Creutzfeldt-Jakob disease, and the search for new mutations in PRNP gene.
AB  - Polymorphism at codon 129 of the prion protein gene (PRNP) is implicated both in
      susceptibility and phenotype of human prion diseases. We characterized the valine
      and methionine allele frequency at codon 129 in 109 individuals representing the
      normal Polish population and in 15 Polish CJD cases. The distribution of the
      genotype was 45% Met/Met, 39% Met/Val, and 16% Val/Val in the control group
      whereas, of the CJD cases, 73.3% were homozygous for methionine, 13.3% homozygous
      for valine and 13.3% were heterozygous. The novel missense mutation (ATG-->ACG)
      at codon 232 was identified in one of the samples with a GSS phenotype.

PMID- 11584449
TI  - Unbiased high resolution method of EEG analysis in time-frequency space.
AB  - Matching Pursuit (MP)--a method of high-resolution signal analysis--is described
      in the context of other methods operating in time-frequency space. The method
      relies on an adaptive approximation of a signal by means of waveforms chosen from
      a very large and redundant dictionary of functions. The MP performance is
      illustrated by simulations and examples of sleep spindles and slow wave activity
      analysis. An improvement of the original procedure, relying on the introduction
      of stochastic dictionaries, is proposed. A comparison of the performance of
      dyadic and stochastic dictionaries is presented. MP with stochastic dictionaries
      is characterized by an unmatched resolution in time-frequency space; moreover it
      allows for parametric description of all (periodic and transient) signal features
      in the framework of the same formalism. Matching pursuit is especially suitable
      for analysis of non-stationary signals and is a unique tool for the investigation
      of dynamic changes of brain activity.

PMID- 11584450
TI  - Conscious control of movements: increase of temporal precision in voluntarily
      delayed actions.
AB  - The variability of simple actions with response to auditory stimuli was studied
      under different delay conditions. Subjects reacted as fast as possible or with a
      defined time delay (from 250 to 750 ms) to a tone switching off by pressing a
      response-key with the left index finger (controlled by the right hemisphere) or
      with the right one (left hemisphere). For short delays (requested response times
      below 350 ms) variability of responses was much larger then for longer delays
      (above 350 ms), especially for the right hand. Thus, precise temporal control on
      consciously mediated actions sets only in after a rather long delay (in some
      cases after half a second). Neuronal mechanisms underlying conscious temporal
      control of actions appear to be different for the two hemispheres.

PMID- 11584451
TI  - Randomized clinical studies: an ethical concern.

PMID- 11584453
TI  - Quadruple pads approach for external cardioversion of atrial fibrillation.
AB  - This study examined the alternative of transthoracic quadruple pads shock
      delivery of two simultaneous 360-J shocks to convert refractory AF in patients
      failing standard external cardioversion. Forty-six patients (mean age 58 +/- 11
      years, 23 men) with chronic AF (duration 14 +/- 17 months, range 1-60 months)
      were included. The left atrial diameter was 47 +/- 7 mm. The left ventricular
      ejection fraction was 59 +/- 11%. Antiarrhythmic drugs had failed to convert 44
      (96%) of these patients. All patients underwent conventional external
      transthoracic cardioversion with pads applied in the antero-apical position using
      energy settings of 200 and 360 J, consecutively. In all patients who failed
      conventional cardioversion, quadruple pads were applied. Quadruple pads consisted
      of four pads, two in the antero-posterior position and two in a second apex
      posterior position. Standard cardioversion to sinus rhythm was successful in 19
      (41%) patients after use of a single 200-J shock and an additional 8 (17%) after
      a single 360-J shock. The total success rate was 58% after conventional
      cardioversion. The quadruple pads were successful in 14 (74%) of the remaining 19
      patients. Four of the five patients who failed the quadruple pads approach
      subsequently also failed internal cardioversion. Thus, the cardioversion success
      rate was increased from 48% using the conventional approach to 89% using the
      quadruple pads approach. Quadruple pads external cardioversion is highly
      effective in converting chronic AF refractory to standard shock protocols to
      sinus rhythm. Moreover, the failure of the quadruple pads approach seems to
      predict poor response to internal cardioversion.

PMID- 11584452
TI  - Radiofrequency energy modification of the atrioventricular junction in patients
      with atrial fibrillation: modes of ventricular response under autonomic blockade
      and long-term effect.
AB  - The short- and long-term effect of radiofrequency (RF) modification of the AV
      junction on ventricular rate and left ventricular function and the different
      types of ventricular response during energy application under autonomic nervous
      blockade were assessed in 28 patients with medically refractory atrial
      fibrillation. During the successful RF application, ventricular rate slowed
      progressively (type I response, ten patients) or accelerated at first and then
      slowed (type II response, 11 patients). Type II response was associated with a
      more anterior ablation site compared to Type I response. A primary successful
      outcome was achieved in 21 patients. Inadvertent complete AV block developed in
      three patients, while in four patients AV nodal ablation was performed after an
      unsuccessful modification attempt. During 6-month follow-up, the ventricular rate
      was adequately controlled in only four patients. Among the 16 patients with a
      recurrence of uncontrolled AF were all 10 patients with type I response and 6 of
      11 patients with type II response. One patient died suddenly 10 weeks after the
      procedure.

PMID- 11584454
TI  - Enhanced detection criteria in implantable cardioverter defibrillators:
      sensitivity and specificity of the stability algorithm at different heart rates.
AB  - The lack of specificity in the detection of ventricular tachyarrhythmias remains
      a major clinical problem in the therapy with ICDs. The stability criterion has
      been shown to be useful in discriminating ventricular tachyarrhythmias
      characterized by a small variation in cycle lengths from AF with rapid
      ventricular response presenting a higher degree of variability of RR intervals.
      But RR variability decreases with increasing heart rate during AF. Therefore, the
      aim of the study was to determine if the sensitivity and specificity of the
      STABILITY algorithm for spontaneous tachyarrhythmias is related to ventricular
      rate. Forty-two patients who had received an ICD (CPI Ventak Mini I, II, III or
      Ventak AV) were enrolled in the study. Two hundred ninety-eight episodes of AF
      with rapid ventricular response and 817 episodes of ventricular tachyarrhythmias
      were analyzed. Sensitivity and specificity in the detection of ventricular
      tachyarrhythmias were calculated at different heart rates. When a stability value
      of 30 ms was programmed the result was a sensitivity of 82.7% and a specificity
      of 91.4% in the detection of slow ventricular tachyarrhythmias (heart rate < 150
      beats/min). When faster ventricular tachyarrhythmias with rates between 150 and
      169 beats/min (170-189 beats/min) were analyzed, a stability value of 30 ms
      provided a sensitivity of 94.5% (94.7%) and a specificity of 76.5% (54.0%). For
      arrhythmia episodes > or = 190 beats/min, the same stability value resulted in a
      sensitivity of 78.2% and a specificity of 41.0%. Even when other stability values
      were taken into consideration, no acceptable sensitivity/specificity values could
      be obtained in this subgroup. RR variability decreases with increasing heart rate
      during AF while RR variability remains almost constant at different cycle lengths
      during ventricular tachyarrhythmias. Thus, acceptable performance of the
      STABILITY algorithm appears to be limited to ventricular rate zones < 170
      beats/min.

PMID- 11584455
TI  - Three-dimensional distribution of bipolar atrial electrogram voltages in patients
      with congenital heart disease.
AB  - Voltage differences might be used to distinguish normal atrial tissue from
      abnormal atrial tissue. This study was aimed at identifying lowest voltage areas
      in patients with atrial tachycardia after surgical correction of congenital heart
      disease and to evaluate if identification of these areas in diseased hearts
      facilitates selection of critical conduction pathways in reentrant circuits as
      target sites for catheter ablation. Ten patients (four men, age 39 +/- 15 years)
      with normal sized atria and atrioventricular reciprocating tachycardia (control
      group) and ten patients (5 men, 32 +/- 7 years) with congenital heart disease and
      postoperative atrial tachycardia (CL 281 +/- 79 ms) referred for radiofrequency
      catheter ablation were studied. Mapping and ablation was guided by a three
      dimensional electroanatomic mapping system (CARTO) in all patients. In the
      control group, voltage maps were constructed during sinus rhythm and during
      tachycardia to evaluate the voltage distribution. The amplitude of bipolar
      signals was 1.90 +/- 1.45 mV (0.11-8.12 mV, n = 660) during sinus rhythm and 1.45
      +/- 1.66 mV (0.12-5.83 mV, n = 440, P < 0.05) during atrioventricular
      reciprocating tachycardia. In the study group, the amplitude of 1,962 bipolar
      signals during tachycardia was 1.01 +/- 1.19 mV (0.04-9.40 mV), which differed
      significantly from the control group during tachycardia (P < 0.0001). No
      significant difference in the tachycardia cycle length was found (P < 0.05)
      between the control and study groups. As the lowest voltage measured in normal
      hearts was 0.1 mV, this value was used as the upper limit of the lowest voltage
      areas in the patients with congenital heart disease. These areas were identified
      by detailed voltage mapping and represented by a gray color. Activation and
      propagation maps were then used to select critical conduction pathways as target
      sites for ablation. These sites were characterized by fragmented signals in all
      patients. Ablation resulted in termination of the tachycardia in eight (80%) of
      ten patients. Complications were not observed. Identification of the lowest
      voltage areas using a cut-off value of 0.1 mV in congenital heart disease
      patients with postoperative atrial reentrant tachycardia facilitated the
      selection of critical conduction pathways as target sites for ablation.

PMID- 11584456
TI  - Bidirectional defibrillation using implantable defibrillators: a prospective
      randomized comparison between pectoral and abdominal active generators.
AB  - The objective of this study was to compare the effects of active abdominal and
      pectoral generator positions on DFTs in a bidirectional tripolar ICD system.
      Twenty-five consecutive patients had ICD systems implanted under general
      anesthesia. A transvenous single lead bipolar defibrillation system and an active
      57-cc test emulator in the abdominal and pectoral positions were used in the same
      patient. A randomized, alternating step-down protocol was used starting at 15 J
      with 3-J decrements until failure. The mean implantation time was 114 +/- 23
      minutes, the mean arrhythmia duration was 14.5 +/- 1.5 seconds, and the mean
      recovery time was 5.4 +/- 1.1 minutes. The mean DFTs in the abdominal and
      pectoral positions were 10.9 +/- 5.1 and 9.7 +/- 5.2 J, respectively (NS), the
      mean intraindividual DFT difference (abdominal minus pectoral) was -0.89 +/- 4.15
      J (range -9.5 to 8 J). The 95% confidence interval showed a -2.60 to +0.82 J mean
      difference (NS). The DFT was < 15 J in 72% and 88% of the patients and the
      defibrillation impedance was 41 +/- 3 and 44 +/- 3 omega, abdominal versus
      pectoral positions. There was no difference in DFT between active abdominal and
      pectoral generator bidirectional tripolar defibrillation. The pectoral position
      may be considered the primary option, but in cases of high DFTs the abdominal
      site should be considered an alternative to adding a subcutaneous patch. In some
      patients, the anatomy may favor an abdominal position. Possible differences in
      the long-term functionality on the leads are not yet well known and need to be
      further evaluated.

PMID- 11584457
TI  - Correlation between defibrillation shock outcome and coherence in
      electrocardiograms.
AB  - Cycle periods in ECG during VF are correlated with periods of reentrant
      activation. The ECGs recorded from different locations on the thorax were
      contributed to from electrical activations within the heart in approximately
      inverse proportion of their distance from the recording sites. Similarity in
      cycle periods between ECGs recorded from two locations, therefore, can be used as
      an index of spatiotemporal similarity in the rate of activation. In the present
      study coherence was used, which is a mathematical function that measures the
      degree of similarity that two signals exhibit at specific cycle periods, to test
      if spatiotemporal similarity in cycle periods between pairs of orthogonal ECGs
      was correlated with defibrillation shock outcome. The authors estimated time
      varying coherence from orthogonal ECGs during 10 seconds of electrically induced
      VF, which was terminated with a defibrillation shock with a 50% probability of
      successful outcome. Defibrillation shocks were delivered between a coil electrode
      placed at the right ventricular apex and a subdermal patch electrode. Time
      varying coherencies between pairs of ECGs were estimated using an adaptive least
      mean square algorithm. Time-coherence surfaces were integrated within a frequency
      region centered at the dominant frequency. Data were collected from ten dogs
      during 206 (48%) successful and 221 (52%) unsuccessful trials. The results showed
      that coherencies between the sagittal-transverse pair were 10%-15% higher (P <
      0.05) for successful than unsuccessful trials. The correlation between coherence
      and defibrillation outcome suggests that more defibrillation shocks occurred when
      the degree of spatial similarity in the rate of activations was higher terminated
      VF, than those that occurred at other times. These results are consistent with a
      hypothesis, recently proposed by others, that more uniform activation within
      regions of the heart that receive low potential gradients during shock may
      increase the probability of successful defibrillation.

PMID- 11584458
TI  - Response of atrial fibrillatory activity to carotid sinus massage in patients
      with atrial fibrillation.
AB  - In some cases carotid sinus massage (CSM) may induce AF, whereas it may terminate
      AF in others. The purpose of this study was to investigate the influence of CSM
      on atrial fibrillatory frequency using spectral analysis of the surface ECG.
      Continuous ECG recordings were made in 19 patients (12 men, 7 women, mean age 61
      +/- 11 years) with AF. Unilateral CSM was performed in the standard fashion to
      one randomized bifurcation of the carotid artery at a time. Ventricular rate and
      fibrillatory frequency were assessed in 30-second ECG segments at baseline and
      during CSM. The frequency content of the fibrillatory baseline was quantified
      using digital signal processing (filtering, subtraction of averaged QRST
      complexes, and Fourier transformation). CSM resulted in a relative change in
      fibrillatory frequency of 4.5 +/- 3.9% (range 0%-13%). In 8 (42%) patients an
      increase in fibrillatory frequency was found (6.4 +/- 0.5 vs 6.8 +/- 0.5 Hz, P =
      0.012). In 9 (47%) patients a decrease in fibrillatory frequency occurred (6.5 +/
      0.8 vs 6.1 +/- 0.8 Hz, P = 0.008) without AF termination. The remaining two
      patients showed no change in fibrillatory frequency. CSM on the contralateral
      side after 2 minutes produced fibrillatory frequency changes in the same
      direction in all patients with a good reproducibility in its magnitude (r = 0.59,
      P = 0.05). Calcium channel blockers were more frequently used (78% vs 25%, P =
      0.044) in patients with a decrease in fibrillatory frequency compared to patients
      with a frequency increase. There were no significant changes in ventricular rate
      during CSM. In conclusion, two different responses of atrial fibrillatory
      frequency to CSM were found. This might explain why CSM may facilitate AF
      induction in some cases and AF termination in others. Calcium channel blocker
      treatment may prevent an increase in fibrillatory frequency provoked by CSM
      suggesting a blunted electrical remodeling process.

PMID- 11584460
TI  - Reduction of pacing output coupling capacitance for sensing the evoked response.
AB  - Sensing of the intracardiac evoked response (ER) after a pacing stimulus has been
      used in implantable pacemakers for automatic verification of capture. Reliable
      detection of ER is hampered by large residual afterpotentials associated with
      pacing stimuli. This led to the development of various technological solutions,
      like the use of triphasic pacing pulses and low polarizing electrode systems.
      This study investigated the effect of reducing the coupling capacitance (CC) in
      the pacemaker output circuitry on the magnitude of afterpotential, and the
      ability to automate detection of ventricular evoked response. A CC of 2.2 microF
      and four different blanking and recharge time settings were clinically tested to
      evaluate its impact on sensing of the ventricular ER and pacing threshold. Using
      an automatic step-down threshold algorithm, 54 consecutive patients, aged 70 +/-
      10 years with acutely (n = 27) or chronically (n = 27) implanted ventricular
      pacing leads were enrolled for measurement testing. Routine measurements, using a
      standard pacing system analyzer (PSA), were (mean +/- SD) impedance 569 +/- 155
      omega, R wave amplitude baseline to peak 9.8 +/- 3.7 mV and threshold 0.9 +/- 0.7
      V at 0.4-ms pulse width. This new capture verification scheme, based on a CC of
      2.2 microF and recharge/blanking timing setting of 10/12 ms, was successful in 52
      patients which is equivalent to a success rate of 96%. In a subgroup of 26
      patients implanted with bipolar ventricular leads (10 chronic, 16 acute), data
      were collected in unipolar (UP) and bipolar (BP) pace/sense configurations. Also,
      ER signals were recorded with two different band-pass filters: a wider band (WB)
      of 6-250 Hz and a conventional narrow band (NB) of 20-100 Hz. WB sensing from UP
      lead configuration yielded statistically significant larger signal to artifact
      ratios (SAR) than the other settings (P < 0.01). A dedicated unipolar ER sensing
      configuration using a small output capacitor and a wider band-pass filter enables
      adequate automatic capture verification, without any restrictions on pacing lead
      models or pacing/sensing configurations.

PMID- 11584459
TI  - Ventricular endocardial right bifocal stimulation in the treatment of severe
      dilated cardiomyopathy heart failure with wide QRS.
AB  - The QRS widening by ventricular conventional pacing impairs the systolic and
      diastolic functions and increases mitral regurgitation. The aim of this study was
      to compare conventional pacing to an alternative stimulation mode with a narrower
      QRS using two leads in the RV. Thirty-nine (25 men, 14 women; mean age 60.1 +/-
      15.1 years) dilated cardiomyopathy patients (Chagas' disease [n = 17],
      coronariopathy [n = 9], AV ablation for tachycardiomyopathy [n = 3], and other [n
      = 10]) with cardiac failure (NYHA 3.1 +/- 0.8), pacemaker indication, and chronic
      AV block (22 AF) had endocardial pacemaker implantations (27 Biotronik, 12
      Guidant). Two RV leads (one septal, one conventional [RV apex] were connected,
      respectively, to the atrial and ventricular pacemaker plugs. After clinical
      stabilization they were studied under three stimulation modes in the same
      session: AAI (septal), VVI (conventional), and ventricular endocardial right
      bifocal stimulation (VERBS) (DDT/DVI/DDD = AV interval = 15/10 ms). In comparison
      to conventional pacing, VERBS increased ejection fraction (0.124), cardiac output
      (19.5%), and peak filling rate (31.0%), and decreased QRS duration (24.7%), left
      atrium area (11.9%), mitral regurgitation area (32.3%), the diastolic transmitral
      flow (E/A relation) (19.3%), and the propagation flow time (18.0%) from the
      mitral valve to the left ventricular apex (tE_col), (P < 0.05). The quality-of
      life showed an impressive score reduction of 50.4%. The septal stimulation alone
      showed a less expressive benefit. In severe dilated cardiomyopathy with classic
      pacemaker indication, VERBS showed significantly better performance than the
      septal or the conventional stimulation alone. There was a good systolic and a
      remarkable diastolic improvement causing an important reduction in the quality-of
      life score.

PMID- 11584461
TI  - Incidence and predictors of pacemaker dysfunction with unipolar ventricular lead
      configuration. Can we identify patients who benefit from bipolar electrodes?
AB  - Unipolar ventricular leads were implanted in a considerable percentage of
      pacemaker recipients. There is little information on incidence and risk factors
      for unipolar pacemaker dysfunction using modern lead designs. Included in a cross
      sectional analysis were 682 patients who fulfilled the following criteria:
      chronically implanted bipolar ventricular leads (> 1 year), intraoperative
      stimulation threshold < 1.0 V/0.5 ms, and potential amplitude > 6 mV. Incidences
      of chest wall stimulation (CWS) at an output of twice the amplitude threshold and
      of myopotential oversensing (MPO) at a sensitivity of half the sensing threshold
      were assessed. Energy (0.60 [0.72] vs 0.63 [0.81] microJ) and sensing thresholds
      (8.31 [3.18] mV vs 8.47 [3.47] mV) did not differ between uni- and bipolar modes.
      While all pacemakers worked properly during bipolar configuration, malfunctions
      were observed in 5.9% of patients during unipolar configuration (CWS = 1.9%, MPO
      = 4.2%). Patient age > 76 years (hazard ratio HR 8.2; P < 0.001), heart failure >
      or = NYHA Class II (HR 3.8; P < 0.001), and an antiarrhythmic therapy with Class
      I or III drugs (HR 3.3; P = 0.002) were independently associated with the
      occurrence of unipolar pacemaker dysfunction. Use of steroid-eluting leads
      reduced the probability of pacemaker dysfunction (HR 0.45; P = 0.03). Risk
      factors for unipolar ventricular pacemaker malfunction were higher age, heart
      failure, and antiarrhythmic drug therapy. Particularly in these patients, use of
      bipolar ventricular leads is beneficial.

PMID- 11584462
TI  - Combined cardiomyopathy and skeletal myopathy: a variant with atrial fibrillation
      and ventricular tachycardia.
AB  - This article describes a family characterized by combined cardiomyopathy and
      nonspecific skeletal myopathy who present in the third to fifth decades with
      cardiac manifestations but earlier have evidence of subtle skeletal muscle
      dysfunction. They differ from previously defined syndromes and potentially
      represent a different genetic expression or mutation. Cardiomyopathy presents
      with atrial arrhythmias including AF and atrial flutter. Life-threatening
      ventricular tachyarrhythmias occur next with onset of ventricular dysfunction.
      Electrophysiological study revealed sustained monomorphic VT. Affected family
      members benefitted from an ICD and progression to congestive heart failure (CHF)
      occurred late. Skeletal myopathy continues with marked progressive muscle
      weakness and inability to ambulate without assistance. Genetic analysis is
      currently ongoing. Neurological evaluation in all three family members revealed
      nonspecific myopathy affecting the psoas and iliopsoas muscles. Atrophy and
      wasting of the facial and temporalis muscles were common. Skeletal muscle biopsy
      revealed myofiber atrophy consistent with myopathy.

PMID- 11584463
TI  - Ibutilide induced intraatrial Wenckebach periodicity in the neonatal canine
      heart.
AB  - In nine anesthetized canine neonates, the high right atrium was paced at
      progressively shorter cycle lengths while recording high right atrial
      electrograms and left atrial appendage monophasic action potentials before and
      after the administration of the new Class III agent, ibutilide. Prior to
      ibutilide administration, 1:1 conduction was maintained from the high right
      atrium to the left atrial appendage at all paced cycle lengths, down to 160 ms.
      Following ibutilide, a pattern of intraatrial conduction was observed in two of
      nine neonates at a cycle length of 160 ms that was consistent with the
      development of intraatrial Wenckebach periodicity. This represents one of the
      only demonstrations of drug induced intraatrial Wenckebach periodicity in vivo
      and suggests that this rarely reported form of atrial conduction block might play
      a role in ibutilide's clinical efficacy against atrial arrhythmias.

PMID- 11584464
TI  - Catheter ablation of ventricular tachycardia in patients with coronary heart
      disease. Part II: Clinical aspects, limitations, and recent developments.

PMID- 11584465
TI  - Bidirectional ventricular tachycardia after radiofrequency ablation of idiopathic
      left ventricular tachycardia.

PMID- 11584466
TI  - When is a nightmare really a nightmare?

PMID- 11584467
TI  - Rise of defibrillation energy requirement under carvedilol therapy.
AB  - Carvedilol, a nonselective beta 1-, beta 2-adrenoreceptor blocking agent with
      alpha 1-adrenoreceptor blocking activity, is often prescribed as an adjunctive
      pharmacological therapy in patients who received an ICD. Despite the new ICD
      technology, concomitant antiarrhythmic therapy still represents the most
      important concern in patients with an ICD. As illustrated by this case,
      carvedilol may also increase the energy requirement for internal defibrillation.

PMID- 11584468
TI  - Quinidine induced electrocardiographic normalization in two patients with Brugada
      syndrome.
AB  - Two patients with Brugada syndrome are presented. The ECGs showed right
      precordial J waves and ST-segment elevation. Patient 1 was resuscitated from
      nocturnal ventricular fibrillation, patient 2 was asymptomatic. In only patient
      1, flecainide was infused causing monomorphic "malignant" ventricular
      extrasystoles (R on T), demonstrating the deleterious effect of Class IC
      antiarrhythmic drugs in Brugada syndrome. However, administration of the Class Ia
      antiarrhythmic drug quinidine caused normalization of the ECG in both patients.
      Based on in vitro experiments, agents that reduce the magnitude of Ito-mediated
      phase 1 have been suggested to normalize ST-segment elevation in Brugada
      syndrome. This is the first clinical report of such a quinidine induced ECG
      normalization.

PMID- 11584469
TI  - Wolff-Parkinson-White syndrome associated with Brugada syndrome.

PMID- 11584471
TI  - Catheter ablation of a right atrial appendage to the right ventricle connection
      in a neonate.
AB  - A neonate with incessant supraventricular tachycardia refractory to multiple
      antiarrhythmic medications was referred to our institution for radiofrequency
      ablation. An unusual accessory pathway between the right atrial appendage and
      right ventricle was successfully ablated. This case also emphasizes the
      congenital origin of such an accessory pathway.

PMID- 11584470
TI  - Hyperkalemia induced pacemaker far-field endless loop tachycardia.
AB  - This report describes the induction of a far-field endless loop tachycardia by
      hyperkalemia in a patient with severe heart disease. Ventricular activation was
      so prolonged that the atrial channel sensed the far-field ventricular deflection
      within the atrial electrogram beyond the 300 ms postventricular atrial refractory
      period.

PMID- 11584472
TI  - Subthreshold stimulation at the focal origin of para-Hisian-located ectopic
      atrial tachycardia.
AB  - The focal origin of ectopic atrial tachycardia (EAT) is occasionally located in
      the superoparaseptal region adjacent to the bundle of HIS. Radiofrequency
      catheter ablation (RFCA) of EAT in this anatomic location implies the potential
      hazard of adverse impairment of the AV conduction. Therefore, careful precise
      mapping is mandatory. Subthreshold stimulation as defined as the delivery of
      noncaptured low energy pulses has been introduced as an additional mapping
      technique for slow pathway ablation in the setting of AV nodal reentrant
      tachycardia and other reentrant tachycardia. A patient with a right
      superoparaseptal EAT focus, in which subthreshold stimulation (STS) could
      determine the site of successful subsequent RFCA is described. During STS with
      EAT termination no AV conduction disturbances, junction-escape rhythms or atrial
      capture could be recorded. Thus STS may be used as an additional mapping tool to
      identify successful ablation sites in EAT.

PMID- 11584473
TI  - Postpericardiotomy syndrome and cardiac tamponade as a late complication after
      pacemaker implantation.
AB  - In a 78-year old woman, pacemaker implantation was complicated by a transient
      perforation of the endocardial lead. The patient was in stable condition for up
      to 7 weeks after implantation, after which pericardial effusion and subacute
      cardiac tamponade developed and pericardiocentesis became necessary. This case
      illustrates that even after initially uneventful pacemaker lead perforation,
      careful, long-term follow-up is necessary to recognize the potential development
      of late postpericardiotomy syndrome.

PMID- 11584474
TI  - Report of the NASPE/NHLBI round table on future research directions in atrial
      fibrillation.

PMID- 11584475
TI  - The STIMAREC bulletin.

PMID- 11584476
TI  - Does prayer influence the success of in vitro fertilization-embryo transfer?
      Report of a masked, randomized trial.
AB  - OBJECTIVE: To assess the potential effect of intercessory prayer (IP) on
      pregnancy rates in women being treated with in vitro fertilization-embryo
      transfer (IVF-ET). STUDY DESIGN: Prospective, double-blind, randomized clinical
      trial in which patients and providers were not informed about the intervention.
      Statisticians and investigators were masked until all the data had been collected
      and clinical outcomes were known. The setting was an IVF-ET program at Cha
      Hospital, Seoul, Korea. IP was carried out by prayer groups in the United States,
      Canada and Australia. The investigators were at a tertiary medical center in the
      United States. The patients were 219 women aged 26-46 years who were
      consecutively treated with IVF-ET over a four-month period. Randomization was
      performed after stratification of variables in two groups: distant IP vs. no IP.
      The clinical pregnancy rates in the two groups were the main outcome measure.
      RESULTS: After clinical pregnancies were known, the data were unmasked to assess
      the effects of IP after assessment of multiple comparisons in a log-linear model.
      The IP group had a higher pregnancy rate as compared to the no-IP rate (50% vs.
      26%, P = .0013). The IP group showed a higher implantation rate (16.3% vs. 8%, P
      = .0005). Observed effects were independent of clinical or laboratory providers
      and clinical variables. CONCLUSION: A statistically significant difference was
      observed for the effect of IP on the outcome of IVF-ET, though the data should be
      interpreted as preliminary.

PMID- 11584477
TI  - Repeated antenatal corticosteroid treatments. Do they reduce neonatal morbidity?
AB  - OBJECTIVE: To compare the effectiveness of single, as compared to multiple,
      courses of antenatal steroid treatments in reducing neonatal morbidity. STUDY
      DESIGN: A retrospective chart review of 204 patients who delivered preterm and
      received antenatal corticosteroids between June 1996 and December 1998 was
      performed and data extracted. All patients who delivered prior to 35 weeks of
      gestation and received corticosteroids were included. The number of antenatal
      treatments was chosen by the obstetrician caring for the patient as well as by
      the opportunity to administer steroids. RESULTS: There were 61 patients in the
      multiple-course group. Gestational age was greater in the multiple-course group
      (31.6 vs. 30.6, P = 0.3), but Apgar scores, neonatal hospital stay, specific
      neonatal morbidity and combined morbidity were not different between the two
      groups. Combined neonatal morbidity was higher after three courses of antenatal
      steroids (29% vs. 50%). Logistic regression analyses adjusting for gestational
      age suggest a possible adverse effect of multiple courses, development of
      respiratory distress syndrome (odds ratio 1.3; confidence interval 1.02; 1.8; P =
      .02) and combined neonatal morbidity (odds ratio 1.3; confidence interval 1.04;
      1.7; P = .02). CONCLUSION: Weekly antenatal steroids do not improve neonatal
      morbidity.

PMID- 11584478
TI  - Color Doppler ultrasonography for distinguishing myomas from uterine contractions
      in pregnancy.
AB  - OBJECTIVE: To determine the applicability and reliability of color Doppler
      ultrasonography (US) for distinguishing a uterine myoma from a focal myometrial
      contraction. STUDY DESIGN: Images from 36 patients with uterine thickenings were
      classified as myomas when color Doppler US demonstrated no centralized flow with
      a circumscribed vessel pattern at the border. Thickenings were classified as
      focal myometrial contractions when there was demonstrable vascular flow
      throughout the thickening. RESULTS: Using these diagnostic criteria, images from
      36 patients were reliably characterized as representing myomas or contractions.
      The diagnosis was made more reliable by using the lowest velocity settings and
      exclusion of power Doppler US in nonretroplacental lesions. CONCLUSION: Color
      Doppler US is a sensitive and reliable tool for distinguishing uterine myomas
      from focal myometrial contractions.

PMID- 11584479
TI  - Significance of benign endometrial cells in Pap smears from postmenopausal women.
AB  - OBJECTIVE: To assess the significance of benign exfoliated endometrial epithelial
      or stromal cells on cervicovaginal Pap smears obtained from postmenopausal women
      not receiving exogenous hormones. STUDY DESIGN: A computerized search of the
      cytology database at two institutions was performed for a five-year period, and
      all cervical cytology cases from postmenopausal patients diagnosed with benign
      endometrial cells were identified. Those cases with histologic follow-up within
      12 months of the original cytologic evaluation were selected for analysis, and
      their cytology and surgical pathology slides were reviewed. RESULTS: A total of
      227 postmenopausal women with benign endometrial cells were identified. Of the 61
      patients with histologic follow-up, 25 (41%) had significant endometrial
      diseases, including hyperplasia without atypia (11), atypical endometrial
      hyperplasia (5), well-differentiated adenocarcinoma (8) and high grade serous
      carcinoma (1). Benign diagnoses, including atrophy (15), weakly proliferative
      endometrium (9) and proliferative endometrium (6), were noted in 30 patients
      (49%). Endometrial polyp was identified in three patients (5%). There were three
      cases of nondiagnostic histologic specimens that lacked endometrial tissue (5%).
      Two of nine women (22%) with proven carcinoma were asymptomatic. CONCLUSION: The
      diagnosis of endometrial cells, cytologically benign, in a postmenopausal woman
      not receiving hormone on Pap smears is associated with a significant number of
      cases of endometrial hyperplasia, atypical hyperplasia and carcinoma.

PMID- 11584480
TI  - Managing atypical squamous cells of undetermined significance in Papanicolaou
      smears.
AB  - OBJECTIVE: To assess strategies using repeated conventional Pap smear and human
      papillomavirus (HPV) DNA testing, alone or in combination, for identifying women
      with concomitant cervical intraepithelial neoplasia 2 and 3 (CIN 2/3) in women
      with atypical squamous cells of undetermined significance (ASCUS) in their Pap
      smears. STUDY DESIGN: A total of 360 women cytologically diagnosed with ASCUS
      were referred for colposcopy and underwent a repeat Pap smear, a biopsy when
      necessary and HPV testing using three different modes of detection of high
      oncogenic-risk HPV types: 1, first-generation Hybrid Capture test (HC-1) (Digene
      Diagnostics, Gaithersburg, Maryland); 2, second-generation Hybrid Capture test
      (HC-2); and 3, polymerase chain reaction (PCR). RESULTS: Nineteen patients (5.3%)
      had histologic CIN 2/3. The sensitivity and specificity of the repeat Pap smear
      alone for the detection of CIN 2/3 were 73.7% and 62.9%, respectively, when
      referring all women with a repeat Pap smear using an ASCUS-positive threshold.
      The proportion of women referred for colposcopy was 39.0%. When HPV testing for
      high risk was used for identification of women with histologic CIN 2/3,
      sensitivity and specificity were, respectively, 68.4% and 85.9% for HC-1, 89.5%
      and 73.9% for HC-2 and 89.5% and 59.0% for PCR. The rate of referral for
      colposcopy of these three modes of HPV testing was 16.9%, 29.4% and 44.0%,
      respectively. The sensitivity and specificity for identification of women with
      concomitant CIN 2/3 using a combination of repeat cytology showing a low grade
      squamous intraepithelial lesion or high grade squamous intraepithelial lesion
      and/or a test positive for high-oncogenic-risk HPV group were, respectively,
      94.7% and 73.2% when used in combination with HC-2. The referral rate of women
      for colposcopy of this combined strategy was 30.4%. CONCLUSION: As compared to
      the strategy using abnormal repeat Pap smear alone, those using high-risk HPV
      testing with Hybrid Capture showed statistically significantly higher
      specificities and lower proportions of women with ASCUS referred for colposcopy.
      In particular, a promising strategy would be to refer for colposcopy only women
      with repeat Pap smears showing squamous intraepithelial lesion and/or those
      positive for high-risk HPV detected by Hybrid Capture testing.

PMID- 11584481
TI  - Relationship of abnormal vaginal flora, proinflammatory cytokines and idiopathic
      infertility in women undergoing IVF.
AB  - OBJECTIVE: To investigate the prevalence of bacterial vaginosis (BV) and abnormal
      bacterial vaginal flora in an infertile population and correlate with cervical
      cytokine production and in vitro fertilization (IVF) outcome. STUDY DESIGN: In a
      blinded study, 331 asymptomatic IVF patients were evaluated for BV, abnormal
      vaginal flora and cervical cytokine production (interleukin 1 beta [IL-1 beta]
      and IL-8) on the day of oocyte retrieval. All patients received tetracycline
      prophylaxis at the time of oocyte retrieval. RESULTS: BV was identified in 4.2%
      (14/331) of the patients. Patients with idiopathic infertility were more likely
      to have BV than were women with other causes of infertility (P = .02 vs. male
      factor, P = .03 vs. tubal factor and P < .01 vs. endometriosis-associated
      infertility). Patients with abnormal vaginal flora had higher cervical IL-1 beta
      and IL-8 cytokine levels as compared to patients with normal vaginal flora. IL-1
      beta and IL-8 levels in the study subjects correlated highly. No differences were
      detected in IVF outcome parameters based on the vaginal flora determined at the
      time of retrieval. CONCLUSION: Abnormal vaginal flora, including that causing BV,
      is associated with elevated cervical levels of IL-1 beta and IL-8. The induction
      of proinflammatory cytokines by an altered vaginal ecosystem may be a previously
      unrecognized cause of idiopathic infertility.

PMID- 11584482
TI  - Safe, successful nausea suppression in early pregnancy with P-6 acustimulation.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of P-6 acustimulation for the
      relief of nausea and vomiting associated with early pregnancy. STUDY DESIGN:
      Forty-one patients were treated with a P-6 acustimulation device at the Division
      of Maternal-Fetal Medicine, Eastern Virginia Medical School. Pretreatment nausea
      severity, posttreatment nausea relief and device effectiveness were patient rated
      using a 1-5 scale. All neonates were evaluated for congenital abnormalities.
      RESULTS: Pretreatment nausea severity scores for treated patients averaged 4.2,
      with most severe and debilitating nausea rated 5. Posttreatment device
      effectiveness averaged 4.2, with significant or complete relief rated 5. Device
      ease of use averaged 4.3, with very easy to use rated 5. No congenital
      abnormalities were found. CONCLUSION: Because current pharmacologic treatments
      for nausea in early pregnancy are not consistent, efficacious or without unwanted
      side effects or increased teratogenic risks, acustimulation of P-6 in pregnancy
      may prove to be a significant therapeutic alternative.

PMID- 11584483
TI  - Blood cultures for women hospitalized with acute pelvic inflammatory disease. Are
      they necessary?
AB  - OBJECTIVE: To determine the incidence of positive blood cultures and if the
      results affect the clinical management or the duration of hospital stay in
      patients with acute pelvic inflammatory disease (PID). STUDY DESIGN:
      Retrospective study of all patients hospitalized with a diagnosis of acute PID
      from January 1, 1996, to December 31, 1997. RESULTS: Of 93 patients in the study,
      3 had significant bacterial growth from blood culture specimens. The results of
      blood culture specimens did not affect clinical management. CONCLUSION: Routine
      specimens for blood culture may not be needed from patients hospitalized with
      acute PID.

PMID- 11584484
TI  - Failed vacuum extraction. Maternal risk factors and pregnancy outcome.
AB  - OBJECTIVE: To evaluate obstetric risk factors associated with a failed trial of
      vacuum extraction and to assess its pregnancy outcome. STUDY DESIGN: All
      attempted vacuum extractions between the years 1990 and 1998 were identified, and
      a comparison of successful and failed trials of vacuum extraction in singleton,
      vertex deliveries was performed. RESULTS: Of 2,111 trials of vacuum extraction,
      113 (5.4%) cases were complicated by failed extraction and underwent cesarean
      section. Those neonates were significantly more likely to be large for
      gestational age, specifically to weigh > 4,000 g as compared to the controls.
      Patients lacking prenatal care had significantly higher rates of failed vacuum
      extraction trials. While cervical and uterine tears were rather rare, parturients
      who had failed trials of vacuum extraction had significantly higher rates of
      cervical and uterine tears as compared to those with successful vacuum
      extractions. This association remained significant after controlling for a
      previous cesarean section using the Mantel-Hanszel technique. Women from the
      failed vacuum extraction group had significantly higher rates of postpartum
      anemia. Pregnancies complicated by failed vacuum extraction had significantly
      higher rates of intrapartum and postpartum fetal death. Those neonates had
      significantly higher rates of Apgar scores < 7 at one and five minutes.
      CONCLUSION: Failed trial of vacuum extraction is associated with adverse maternal
      and fetal outcomes. Risk factors associated with such failures are fetal weight
      and lack of prenatal care. Thus, careful estimation of fetal weight should be
      performed before the procedure, and estimated fetal weight > 4,000 g might be
      considered a relative contraindication to vacuum extraction, especially among
      patients who did not have prenatal care.

PMID- 11584485
TI  - Risk factors for antepartum fetal death.
AB  - OBJECTIVE: To determine the demographic, maternal, pregnancy-related and fetal
      risk factors for antepartum fetal death (APFD). STUDY DESIGN: From our perinatal
      database between the years 1990 and 1997, 68,870 singleton birth files were
      analyzed. Fetuses weighing < 1,000 g at birth and those with structural
      malformations and/or known chromosomal anomalies were excluded from the study. In
      order to determine independent factors contributing to APFD, a multiple logistic
      regression model was constructed. RESULTS: During the study period there were 246
      cases of APFD (3.6 per 1,000 births). The following obstetric factors
      significantly correlated with APFD in a multiple logistic regression model:
      preterm deliveries: small size for gestational age (SGA), multiparity (> 5
      deliveries), oligohydramnios, placental abruption, umbilical cord complications
      (cord around the neck and true knot of cord), pathologic presentations
      (nonvertex) and meconium-stained amniotic fluid. APFD was not significantly
      associated with advanced maternal age. CONCLUSION: APFD was significantly
      associated with several risk factors. Placental and umbilical cord pathologies
      might be the direct cause of death. Grand multiparity, oligohydramnios, meconium
      stained amniotic fluid, pathologic presentations and suspected SGA should be
      carefully evaluated during pregnancy in order to decrease the incidence of APFD.

PMID- 11584486
TI  - Clinical pathway for evaluating women with abnormal uterine bleeding.
AB  - OBJECTIVE: To devise a clinical pathway for evaluating women with abnormal
      uterine bleeding. STUDY DESIGN: One thousand women with the complaint of abnormal
      uterine bleeding were enrolled. All would have undergone endometrial biopsy based
      on older recommendations. The patients followed a clinical pathway to determine
      if an endometrial biopsy was necessary. The pathway divided women into the
      categories of premenopausal, postmenopausal, low risk and high risk. If one risk
      factor was present, the patient underwent endometrial biopsy. If there were no
      risk factors, the patient continued down the pathway with medical therapy.
      RESULTS: Five hundred seventy endometrial biopsies were performed. Five cases of
      endometrial cancer and three of complex atypical hyperplasia, both in the
      postmenopausal, high-risk group, were discovered. Subsequent reviews revealed
      that no cases of endometrial cancer were missed or developed in the two years
      following the initial complaint. CONCLUSION: Utilization of a clinical pathway
      reduced the number of endometrial biopsies by 50%. The introduction of clinical
      pathways at our institution was done successfully in the evaluation of abnormal
      uterine bleeding.

PMID- 11584487
TI  - Effect of acupressure on nausea and vomiting during pregnancy. A randomized,
      placebo-controlled, pilot study.
AB  - OBJECTIVE: To compare the antiemetic effect of acupressure at the Neiguan point
      (P6) in a group of healthy women with normal pregnancy and nausea and vomiting
      during pregnancy (NVP) with a similar group receiving acupressure at a placebo
      point and another, similar group not receiving any treatment. STUDY DESIGN: A
      randomized, placebo-controlled, pilot study involving 60 women. RESULTS: It is
      possible to reduce NVP significantly with acupressure at P6 as compared to
      acupressure at a placebo point or no treatment at all in healthy women with
      normal pregnancies. Relief from nausea appeared one day after starting treatment
      in both the P6 and placebo groups but lasted for only six days in the placebo
      group. The P6 group, however, experienced significantly less nausea after 14 days
      as compared to the other two groups. CONCLUSION: This study involved 60 healthy
      women with normal pregnancy and suffering from NVP. According to the results, in
      healthy women with normal pregnancy it is possible to reduce NVP significantly at
      P6 as compared to acupressure at a placebo point and to no treatment.

PMID- 11584488
TI  - Previous cesarean section. A contraindication to vaginal hysterectomy?
AB  - OBJECTIVE: To compare surgical outcomes of vaginal hysterectomy between women who
      have had one or more cesarean deliveries and those who have not. STUDY DESIGN: A
      retrospective, chart review study was performed on women undergoing vaginal
      hysterectomy during a four-year period. Of 275 women who met the study criteria,
      104 had a history of previous cesarean deliveries, and 171 did not. The groups
      were compared for indications for surgery, operative time, length of
      hospitalization and surgical complications. RESULTS: Previous cesarean delivery
      did not affect hemoglobin loss, hospital stay or operative time among women
      undergoing vaginal hysterectomy. The complication rate (either operative or
      postoperative) was 12.3% among women without a history of cesarean section, 6.8%
      among those with one, 3.7% among those with two and 11.1% among those with three
      or more (chi 2 = 2.8, P = .4). The odds for surgical complications were not
      significantly different between women with one or more prior cesarean deliveries
      as compared to those without after adjustment for possible confounders.
      CONCLUSION: Surgical complications with vaginal hysterectomy do not appear to be
      higher among women with a prior cesarean section as compared to those without a
      history of such operation.

PMID- 11584489
TI  - Primitive neuroectodermal tumor of the uterus. A case report.
AB  - BACKGROUND: Primitive neuroectodermal tumors (PNETs) of the uterus are very rare.
      Even preoperative curettage specimen morphology does not permit establishing a
      proper histogenetic diagnosis. CASE: A 16-year-old woman was admitted to the
      hospital because of metrorrhagia of three months' duration. The curettage
      specimen was interpreted as poorly differentiated sarcoma. The patient was
      operated on, and a total abdominal hysterectomy with bilateral salpingo
      oophorectomy with omentectomy was performed. Histologically the tumor was
      composed of uniform, rounded, oval and sometimes spindle shaped cells with a
      narrow rim of eosinophilic cytoplasm. The cells were positive for neurogenic
      marker protein gene product, neuron-specific enolase and Ewing's sarcoma-related
      HBA-71. All cells were uniformly negative for Ber EP4 monoclonal antibody
      recognizing an epithelium-specific surface antigen. A diagnosis of PNET was
      rendered. The patient received combined therapy, external radiation to the pelvis
      and chemotherapy. Four years later she was alive, without signs of recurrent
      tumor. CONCLUSION: In spite of the generally recognized aggressive behavior of
      PNET, it can have a long disease-free survival rate when appropriately treated.

PMID- 11584490
TI  - Postpartum herpes simplex endometritis. A case report.
AB  - BACKGROUND: Herpes simplex virus (HSV) can cause postpartum endometritis. The
      clinical diagnosis of HSV endometritis has been reported previously. The disease
      is responsive to acyclovir intravenously. CASE: A 22-year-old woman, gravida 2,
      para 1, status post primary cesarean section for a double footling breech
      presentation, developed a persistent postpartum fever. Simulating the febrile
      course of septic pelvic thrombophlebitis, the patient's condition was
      unresponsive to broad-spectrum antimicrobials and heparin therapy. Active
      herpetic lesions and a positive cervical culture for herpes simplex prompted the
      use of intravenous acyclovir. Rapid resolution of the fever and the similarity to
      previous case reports suggested the clinical diagnosis of herpes simplex
      endometritis. CONCLUSION: The diagnosis of postpartum herpes simplex endometritis
      should be considered when managing a persistent postpartum fever unresponsive to
      aggressive antimicrobial and heparin therapy. Immediate resolution of the fever
      should occur with the use of acyclovir.

PMID- 11584491
TI  - Vesicouterine fistula after vacuum delivery and two previous cesarean sections. A
      case report.
AB  - BACKGROUND: Vesicouterine fistulas are associated with cesarean section and more
      rarely with vaginal birth after cesarean (VBAC). Many surgical approaches exist,
      including hysterectomy. CASE: A vesicouterine fistula was diagnosed after VBAC in
      a 34-year-old multipara with two previous cesarean sections. The defect failed to
      close after four months of bladder drainage. Closure via laparotomy with an
      omental flap and preservation of the uterus was successful. CONCLUSION:
      Vesicouterine fistula can occur after VBAC, and failure of conservative therapy
      can be treated abdominally with preservation of the uterus.

PMID- 11584492
TI  - Explosion of a vulvar hematoma during spontaneous vaginal delivery. A case
      report.
AB  - BACKGROUND: Vulvar hematoma formation during a spontaneous vaginal birth is rare.
      Although conservative management or observation is an option, complications,
      including delivery obstruction and excessive vaginal bleeding, may occur. CASE: A
      woman presented in active labor with an enlarging vulvar hematoma reaching the
      size of a softball. Spontaneous vaginal delivery occurred with an "explosion" of
      the hematoma and excessive blood loss. To obtain hemostasis, the hematoma cavity
      was explored and the bleeding points sutured. CONCLUSION: With a large
      intrapartum vulvar hematoma, the risk of rupture exists. If it occurs, delivery
      should be accomplished expediently, hemostasis achieved rapidly and blood loss
      monitored closely.

PMID- 11584494
TI  - Hand-assisted laparoscopic renal and adrenal surgery.

PMID- 11584493
TI  - Successful pregnancy in an infertile woman with endometrial hyperplasia and
      embryo transfer. A case report.
AB  - BACKGROUND: Successful pregnancy in a woman with complex endometrial hyperplasia
      with atypia was treated conservatively with gestagens. CASE: The patient was
      initially diagnosed with complex hyperplasia of the endometrium with atypia by
      endometrial curettage and treated with several cycles of different gestagens.
      After repeated endometrial curettage, in vitro fertilization and embryo transfer
      were introduced for immediate treatment of the patient's infertility in order to
      avoid the risk of recurrent hyperplasia of the endometrium from estrogens. A
      single pregnancy was achieved after transfer of embryos obtained from
      intracytoplasmic sperm injection. This was performed due to poor semen
      characteristics. The patient delivered a normal, healthy male infant at term.
      CONCLUSION: Conservative treatment of complex endometrial hyperplasia with atypia
      in young women wishing to preserve fertility should be considered in carefully
      selected cases.

PMID- 11584495
TI  - Vaginal breech delivery: will it disappear forever from the delivery room?

PMID- 11584496
TI  - Case report: left bundle branch block--a rare complication of citalopram
      overdose.

PMID- 11584497
TI  - A collaborative clerkship with a focus on rural community health.
AB  - The Deans' Rural Primary Care Clerkship was developed through the collaborative
      efforts of South Carolina's two medical schools. The clerkship provides students
      an innovative learning experience in rural community medicine through the unique
      combination of learning opportunities with community-oriented primary care,
      continuous quality improvement, interdisciplinary health care teams, and cultural
      competency. Much of students' learning addresses current directives for
      population health training. The positive experience students are having in these
      rural, underserved South Carolina communities will help them better understand
      the rewards and challenges of rural, community-responsive health care.

PMID- 11584498
TI  - Fixing a flat tire in the age of managed care.

PMID- 11584499
TI  - Computer aided simulation surgery using a laser-curable resin model: preoperative
      preparation of hydroxyapatite prosthesis for bone defect repair.

PMID- 11584500
TI  - Computer-aided surgery and tissue expansion in auricular reconstruction for
      microtia.

PMID- 11584501
TI  - Historical overview.

PMID- 11584502
TI  - A computer-aided cleft lip simulation surgery system.

PMID- 11584503
TI  - The virtual reality technique in simulation surgery--a mandibular fracture model.

PMID- 11584504
TI  - Telesurgery system in simulation surgery.

PMID- 11584505
TI  - Computer aided simulation surgery and informed consent: implications for the
      patient and the family.

PMID- 11584506
TI  - Computer aided simulation surgery as an educational tool.

PMID- 11584507
TI  - The fourth dimension in simulation surgery for craniofacial surgical procedures.
AB  - The intracranial volume was measured in all 18 cases of craniosynostosis and
      craniofacial synostosis with 3DCT using a modification of Miyake's formula, with
      a 6 years' follow-up. 1: There were no cases where the intracranial volume was
      less than the modified Miyake's formula. 2: Total cranial reshaping, compared to
      the local forehead advancement, was effective in increasing the intracranial
      cavity and growth postoperatively. 3: In cases of craniofacial synostosis, there
      is a possibility that mental retardation will develop if the intracranial volume
      tends to increase rapidly and more than expected.

PMID- 11584508
TI  - Types of simulation surgery.

PMID- 11584509
TI  - Practical considerations in empirical simulation surgery, with special reference
      to plastic surgery.

PMID- 11584510
TI  - The computer and simulation surgery.

PMID- 11584511
TI  - The lattice system and three-dimensional computer modeling.

PMID- 11584512
TI  - The concept of simulation surgery.

PMID- 11584513
TI  - Craniofacial surgical simulation system in the 3 dimensional CT SurgiPlan system.

PMID- 11584514
TI  - Subjective quality of life in the evaluation of programs for people with serious
      and persistent mental illness.
AB  - Despite the widespread application of the concept of quality of life in mental
      health evaluation, it has been observed that subjective quality of life measures
      do not reliably capture changes expected to result from intervention efforts.
      Moreover, because the domains selected to assess subjective life quality are
      typically generated by investigators or health professionals, the validity of
      subjective quality of life measures has also been questioned. Although it
      represents a conceptual shift from investigator-generated domains to client
      elicited domains, it is suggested that a client-elicited approach to measuring
      subjective quality of life may provide fruitful avenues for resolving some of the
      conceptual and practical issues associated with understanding and measuring the
      impact of community-based programs on clients with serious mental illness.
      Accordingly, while acknowledging the utility of assessing the objective
      circumstances of people's lives, this paper suggests that client-elicited
      subjective quality of life domains have the potential to resolve the failure of
      existing measures to register meaningful change. Unlike previous general reviews
      of quality of life that have emphasized measurement issues, the present review
      considers some of the fundamental barriers to our ability to adequately
      understand and document the experiences of people adjusting to community living
      with a psychiatric disability.

PMID- 11584515
TI  - Insomnia: symptom or diagnosis?
AB  - Is insomnia a clinical entity in its own right or is it simply a symptom of an
      underlying medical or psychological disorder? The widely held view among many
      clinicians and researchers is that insomnia is secondary to or an epiphenomenon
      of a 'primary' medical or psychological disorder. Consequently, insomnia
      'symptoms' have tended to be trivialized or ignored. This paper aims to highlight
      the assumptions and implications of distinguishing between 'primary' and
      'secondary' insomnia and reviews the evidence for the distinction by considering
      (1) issues relating to the diagnosis and classification of insomnia, (2) whether
      insomnia is a symptom of other medical and psychological disorders, (3) whether
      insomnia is comorbid with other disorders, (4) whether insomnia is 'secondary' to
      other disorders, and (5) whether insomnia occurs in the absence of comorbidity.
      It is concluded that viewing insomnia as a symptom or epiphenomenon of other
      disorders can be unfounded. This view may deprive many patients of treatment,
      which might not only cure their insomnia, but may also reduce symptoms associated
      with the assumed 'primary' disorder. Finally, directions for future research to
      further illuminate the relationship between insomnia and comorbid disorders are
      discussed.

PMID- 11584517
TI  - A review of individual psychotherapy outcomes for adult survivors of childhood
      sexual abuse.
AB  - This review examines the current literature on individual psychotherapy outcomes
      with adult survivors of childhood sexual abuse. As compared to the literature on
      treatment with victims of sexual trauma in adulthood, fewer researchers have
      explored the field of psychotherapy outcome with this population, particularly
      with regard to individual treatments. For this reason, a review of psychotherapy
      outcome for adult survivors of child sexual abuse is needed. This review first
      presents issues salient to the study of treatment with this population, such as
      prevalence, short-term impact, and long-term sequelae of childhood sexual trauma.
      Next, the eight studies that have been published on individual psychotherapy for
      this population are presented and evaluated according to both efficacy and
      effectiveness criteria for a methodologically sound study. Last, directions for
      future research with this population include continued integration of efficacy
      and effectiveness methodology, use of multi-method/multi-rater assessment data,
      as well as further investigation of interpersonal variables such as the
      therapeutic alliance.

PMID- 11584516
TI  - The Conners' Parent Rating Scales: a critical review of the literature.
AB  - The Conners' Parent Rating Scales (CPRS) have undergone a considerable amount of
      scrutiny--and subsequent refining, reshaping, and revising--since their
      development in 1970. While such longitudinal scrutiny has ultimately led to a
      more reliable, valid assessment tool, it has left behind a wake of literature
      filled with misinformation and ambiguity. Multiple versions of the Conners'
      Rating Scales (CRS), their misuse, and inaccurate reporting by researchers have
      created a body of literature that is difficult to interpret and misleading to
      both researchers and clinicians. This review is aimed at clarifying issues
      regarding the proper use of the CPRS as both a diagnostic instrument and a
      research tool.

PMID- 11584518
TI  - The efficacy of cognitive-behavioral therapy on the core symptoms of bulimia
      nervosa.
AB  - Cognitive behavioral therapy (CBT) is widely regarded as the treatment of choice
      for bulimia nervosa (BN), with previous reviews of the CBT outcome literature
      claiming an approximate 40%-50% recovery rate. Most of these reviews have focused
      on reductions of binge eating and purging; however, the cognitive model of BN
      that underlies the CBT approach identifies three additional symptoms as central
      to the disorder: restrictive eating, concerns with shape and weight, and self
      esteem. The purpose of this review was to determine the effect of CBT on the five
      core symptoms of BN, particularly those neglected in previous reviews. This
      review found that while most studies provided outcome data on binge eating,
      purgative behavior, and concern with shape and weight, fewer studies provided
      data on restraint and self-esteem. While generally favorable, evidence for the
      efficacy of CBT on the core symptoms of BN was mixed, depending on the outcome
      measures used. Shortcomings in the literature are identified and suggestions to
      correct these shortcomings are provided.

PMID- 11584519
TI  - A social cognitive perspective on religious beliefs: their functions and impact
      on coping and psychotherapy.
AB  - Religious beliefs are an important part of clients' culture, whether acknowledged
      or not. Psychological theories about social and cognitive processes can help
      mental-health professionals better understand the function of religious beliefs
      in coping and their role in therapy. Religious individuals are likely to use
      heuristics to form rapid judgments rather than engage in formal information
      gathering processes. The confirmatory and in-group/out-group biases support such
      judgments and shield them from disconfirmatory evidence. Religious beliefs
      provide order and understanding to an otherwise chaotic and unpredictable world.
      Many religions advocate forgiveness, which is often helpful in resolving
      conflicts. Another beneficial religious belief is an ever-present spiritual
      attachment figure. Negative effects of religion include its exercising aversive
      control to maintain conformity and its promoting an external locus of control. In
      contrast, mental-health professionals belong to a tradition of free inquiry and
      self-development, and guide clients to acquire competencies necessary to change
      and direct their lives. Therapist attitudes are far less likely to include
      allegiance to religion than are those of the public and psychiatric patients.
      Rather than being biased against religion or trying to debate religion,
      therapists need to engage in problem solving with clients in the context of this
      example of sociocultural factors.

PMID- 11584520
TI  - [Interview with Dr. M. Feldmann, Bremen. What is your opinion of stroke
      prevention? (interview by M. Koczorek)].

PMID- 11584521
TI  - [New study of selective COX-2 inhibitors. Protecting the stomach while risking
      the heart? (interview by Dr. Beate Schumacher)].

PMID- 11584522
TI  - [No lymphedema, no obesity. How can lipedema be treated?].

PMID- 11584523
TI  - [Epidemiological correlation between coronary heart disease and depression.
      Significant increase in mortality].

PMID- 11584524
TI  - [Mood disorders and coronary heart disease. How depression damages the heart].

PMID- 11584525
TI  - [Heart patient with depressive disorder. Proper treatment method].
AB  - Mild and severe depressive disorders are an independent risk factor for cardiac
      mortality following myocardial infarction, and possibly also for coronary heart
      disease. The depressive symptoms should always be treated despite the fact that
      an influence on the cardiac situation has not (yet) been empirically shown. For
      treatment, selective serotonin re-uptake inhibitors, but also other substances,
      are available, together with brief psychotherapeutic techniques and the promotion
      of social support.

PMID- 11584526
TI  - [Dermatologic emergency situation series. Burns and scalds of the skin].

PMID- 11584527
TI  - [Modern concepts of rosacea therapy. Means and ways to combat erythema and
      rhinophyma. Interview with Dr. med. T. Jansen, Bochum].

PMID- 11584528
TI  - [Secondary hypertension, 4: Pheochromocytoma as etiology of hypertension].

PMID- 11584529
TI  - [Achieving vascular protection. ACE inhibitor lowers not only blood pressure].

PMID- 11584530
TI  - [Ramipril can do more. Halting progression of atherosclerosis].

PMID- 11584531
TI  - [Optimizing treatment of osteoporosis. Rapidly effective therapy lowers fracture
      risk in 1 year up to 70%].

PMID- 11584532
TI  - [Risedronate now also approved for hip fractures. Study discloses significant
      risk reduction in proximal femoral neck fractures].

PMID- 11584533
TI  - [Ketolide antibiotics. A new therapeutic option in respiratory tract infections].

PMID- 11584534
TI  - [Depression and anxiety. Broad spectrum SSRI to control both].

PMID- 11584535
TI  - [Acceptance of antiretroviral therapy. HIV-infected patients assess convenient
      triple combination].

PMID- 11584536
TI  - [Quality of life as the focus of modern anti-HIV treatment. More compact regimens
      for therapy success].

PMID- 11584537
TI  - [ACE inhibitor. Effective blood pressure control around the clock].

PMID- 11584538
TI  - [22. Weight loss of unknown origin--always an alarm symptom!].

PMID- 11584539
TI  - [Psychophysiological aspects of occupational stress in occupational medicine].
AB  - The authors necessitate complex psychophysiologic, hygienic and clinical research
      to form a concept of stress induced by occupational factors. The materials
      disclosure role of fundamental studies, critically review various models (two-
      and three-dimensional) of stress at work. Analysis of the authors' data and facts
      obtained by other researchers in detection and evaluation of various stress
      factors. Essential is to specify prophylactic measures against stress at work for
      workers' health preservation.

PMID- 11584540
TI  - [Cold stress and its prophylaxis].
AB  - The authors present criteria of cold stress and their relationships with
      thermoregulatory strain, ability to work and some health state parameters.
      Findings are unfavorable influence of human cooling and adaptation to cold on
      vibration disease development. The article covers requirements to heat-proof
      properties of clothing set, to duration of exposure to cold in various climate
      areas of Russian Federation.

PMID- 11584541
TI  - [Individual, social and psychologic factors of resistance to stress among
      operators and dispatchers in power plant].
AB  - Study in two operators' groups with high and low levels of psychic stability
      revealed that individuals with high emotional stability, good self-control, low
      frustration and sthenic reactivity type demonstrate higher resistance to
      psychologic stress at work. Opposite personal features lower resistance to stress
      and result in transfer of stress at work into family relationships sphere that
      itself could become a stressor.

PMID- 11584542
TI  - [Influence of stress at work on reliability of astronauts' activities].
AB  - The article presents definition of "stress at work" term, covers principles and
      methods of occupational medicine so as to specify criteria for evaluation and
      regulation of stress at work. Technology of the criteria application is
      exemplified by influence of occupational stress on reliability of astronauts
      activities in simulated docking during spaceflight.

PMID- 11584543
TI  - [Peculiarities of stress at work under various work intensity].
AB  - Complex hygienic approach using psychophysiologic and clinical methods revealed
      features of occupational stress for various work intensity.

PMID- 11584544
TI  - [Stress in school children: causes, consequences, prophylaxis].
AB  - The article presents main causes of stress within school education. Ability to
      work and health state of schoolchildren appeared to be disordered by study
      overload, authoritarian teaching style, traditional exams and underdeveloped
      significant mental skills at the study beginning.

PMID- 11584545
TI  - [Psychophysiological aspects of stress at work in water transport].
AB  - Specific arrangement, character, conditions and work schedule of sailing staff
      provide a complex of stressors. Hygienic and psychophysiologic examinations of
      sailing crews under stress on various ships revealed chronic occupational stress
      and helped to define ways eliminating causes for that stress.

PMID- 11584546
TI  - [Clinical and biochemical changes under exposure to industrial stress factors in
      coal miners].

PMID- 11584547
TI  - [Methodological aspects of evaluating the emotional stress in humans during
      genetic and toxicologic research].

PMID- 11584548
TI  - [Combined effects of psychoemotional stress and carbon monoxide in experiments].
AB  - Psychoemotional stress and exposure to various concentrations of carbon monoxide
      are antagonists or act independently. The results necessitate changes in MAC for
      carbon monoxide in air of workplace.

PMID- 11584549
TI  - Sleep, sleepiness, and alcohol use.
AB  - The study of alcohol's effects on sleep dates back to the late 1930s. Since then,
      an extensive literature has described alcohol's effects on the sleep of healthy,
      nonalcoholic people. For example, studies found that in nonalcoholics who
      occasionally use alcohol, both high and low doses of alcohol initially improve
      sleep, although high alcohol doses can result in sleep disturbances during the
      second half of the nocturnal sleep period. Furthermore, people can rapidly
      develop tolerance to the sedative effects of alcohol. Researchers have
      investigated the interactive effects of alcohol with other determinants of
      daytime sleepiness. Such studies indicate that alcohol interacts with sleep
      deprivation and sleep restriction to exacerbate daytime sleepiness and alcohol
      induced performance impairments. Alcohol's effects on other physiological
      functions during sleep have yet to be documented thoroughly and unequivocally.

PMID- 11584551
TI  - Alcohol, antidepressants, and circadian rhythms. Human and animal models.
AB  - Alcohol consumption (both acute and chronic) and alcohol withdrawal have a
      variety of chronobiological effects in humans and other animals. These effects
      are widespread, altering the circadian rhythms of numerous physiological,
      endocrine, and behavioral functions. Thus, some of alcohol's negative health
      consequences may be related to a disruption of normal physiological timing. Most
      studies of alcohol's chronobiological effects have been conducted under natural
      conditions in which environmental stimuli, such as regular cycles of light and
      darkness, act to coordinate circadian rhythms with the environment and with each
      other. However, such studies cannot distinguish between effects occurring
      directly on the circadian pacemaker and those occurring "downstream" from the
      pacemaker on the physiological control systems. Studies using animals have
      enabled researchers to begin to examine the effects of alcohol on circadian
      rhythms under so-called free-running conditions in experimental isolation from
      potential environmental synchronizers. These studies have provided preliminary
      evidence that alcohol's chronobiological effects are indeed the result of direct
      influences on the circadian pacemaker itself. Furthermore, the effects of alcohol
      on animal circadian rhythms appear similar to the effects seen during
      administration of antidepressant drugs. Taken together with evidence that the
      chronobiological effects of alcohol withdrawal in human alcoholics are
      reminiscent of those described in depressed patients, these observations suggest
      that alcohol may produce antidepressantlike effects on the circadian pacemaker.
      One theory suggests that the effects of alcohol on the circadian pacemaker are
      mediated in part by alterations in serotonin, an important chemical involved in
      cellular communication within the circadian system. However, other neurochemical
      systems also are likely to be involved.

PMID- 11584552
TI  - Developmental alcohol and circadian clock function.
AB  - Studies in rats found that alcohol exposure during the early postnatal period,
      particularly during the brain-growth-spurt period, can result in cell loss in
      various brain regions and persistent behavioral impairments. Some investigators
      have speculated that the body's internal clock, which is located in the
      suprachiasmatic nuclei (SCN) in the brain, may also be affected by developmental
      alcohol exposure. For example, alcohol-induced damage to the SCN cells and their
      function could result in disturbances of the circadian timekeeping function, and
      these disturbances might contribute to the behavioral impairments and affective
      disorders observed in people prenatally exposed to alcohol. Preliminary findings
      of studies conducted in rats suggest that developmental alcohol exposure may
      indeed interfere with circadian clock function as evidenced by a shortened
      circadian sleep-wake cycle and changes in the release of certain brain chemicals
      (i.e., neuropeptides) by SCN cells.

PMID- 11584550
TI  - Alcohol's effects on sleep in alcoholics.
AB  - Sleep problems, which can have significant clinical and economic consequences,
      are more common among alcoholics than among nonalcoholics. During both drinking
      periods and withdrawal, alcoholics commonly experience problems falling asleep
      and decreased total sleep time. Other measures of sleep are also disturbed. Even
      alcoholics who have been abstinent for short periods of time (i.e., several
      weeks) or extended periods of time (i.e., several years) may experience
      persistent sleep abnormalities. Researchers also found that alcoholics are more
      likely to suffer from certain sleep disorders, such as sleep apnea. Conversely,
      sleep problems may predispose some people to developing alcohol problems.
      Furthermore, sleep problems may increase the risk of relapse among abstinent
      alcoholics.

PMID- 11584553
TI  - Chronobiological regulation of alcohol intake.
AB  - Like other physiological functions, food intake and metabolism (including alcohol
      consumption) in humans and animal models may be regulated by circadian rhythm.
      For example, many studies of rodents have found that alcohol consumption in these
      nocturnal animals peaks during their active dark period. This alcohol consumption
      pattern can be influenced, however, by experimental manipulation. One factor that
      has been proposed to play a role in regulating circadian alcohol consumption
      pattern is the hormone melatonin, which is produced by the pineal gland. Research
      also indicates that the effects of lighting conditions on the alcohol consumption
      of animal models may be influenced by the differences among the strains of the
      laboratory animals used, variations in the type and administration schedule of
      the animals' alcohol-containing diet, disruptions of the normal circadian rhythm,
      concurrent use of other drugs, and properties of the light.

PMID- 11584554
TI  - Overview of circadian rhythms.
AB  - The daily light-dark cycle governs rhythmic changes in the behavior and/or
      physiology of most species. Studies have found that these changes are governed by
      a biological clock, which in mammals is located in two brain areas called the
      suprachiasmatic nuclei. The circadian cycles established by this clock occur
      throughout nature and have a period of approximately 24 hours. In addition, these
      circadian cycles can be synchronized to external time signals but also can
      persist in the absence of such signals. Studies have found that the internal
      clock consists of an array of genes and the protein products they encode, which
      regulate various physiological processes throughout the body. Disruptions of the
      biological rhythms can impair the health and well-being of the organism.

PMID- 11584555
TI  - Alcohol's interactions with circadian rhythms. A focus on body temperature.
AB  - The complex interaction between alcohol and the body's circadian rhythm has
      become a rapidly expanding area in chronopharmacology. This area has key
      implications for the field of alcohol research, because understanding alcohol's
      effects on the body's internal clock will aid scientists in designing medications
      and behavioral interventions for treating alcohol abuse and dependence. A number
      of studies provide evidence that alcohol sensitivity and preference vary with
      circadian timing. However, only a few studies support alcohol's ability to
      influence the circadian phase directly. This review focuses on studies examining
      how alcohol and the body's circadian rhythm interact, using body temperature as
      an index of circadian rhythm function. Though the research is limited, findings
      indicate that alcohol sensitivity and preference for drinking to indeed appear to
      vary with circadian timing and that alcohol may act directly on the central
      pacemaker to alter circadian functioning.

PMID- 11584556
TI  - Look, no strings: publishing industry-funded research.

PMID- 11584557
TI  - The merits of new alternatives to the Papanicolaou test.

PMID- 11584558
TI  - Support groups for people carrying a BRCA mutation.

PMID- 11584560
TI  - Talking cigarette packs are not the answer.

PMID- 11584559
TI  - Funding of global health research.

PMID- 11584561
TI  - Occupational health Web site.

PMID- 11584562
TI  - Completed suicides among the Inuit of northern Quebec, 1982-1996: a case-control
      study.
AB  - BACKGROUND: The rate of completed suicide among Inuit in Canada has been
      alarmingly high in recent years, and the suicide rate among Inuit in northern
      Quebec has increased since 1982. Our objectives were to describe the
      characteristics of Inuit people who died by suicide in Nunavik between 1982 and
      1996, and to identify the antecedents and correlates of completed suicide.
      METHODS: We carried out a case-control study of 71 people who died by suicide
      between 1982 and 1996 and 71 population-based living control subjects matched for
      sex, community of residence and age within 1 year. Comprehensive medical charts
      were reviewed for data on sociodemographic characteristics, medical and
      psychiatric history, childhood separations and family history, and use of health
      care services. RESULTS: Most of the case subjects were single males aged 15 to 24
      years. The two principal means of suicide were hanging (in 39 cases [54.9%]) and
      gunshot (in 21 cases [29.6%]). About 33% had been in contact with medical
      personnel in the month before their death. The case subjects were significantly
      more likely than the control subjects to have received a lifetime psychiatric
      diagnosis (one or more of depression, personality disorder or conduct disorder)
      (odds ratio [OR] 4.3 [95% confidence interval (CI) 1.2-15.2]) and to have had a
      history of psychiatric symptoms, disorder (including solvent sniffing) or
      treatment (OR 3.5 [95% CI 1.4-8.7]). The case subjects had experienced more
      severe types of nonpsychiatric illnesses and injuries than the control subjects
      (p = 0.04). The case subjects had more lifetime contacts with health care
      services than the control subjects (p = 0.01) and were more likely than the
      control subjects to have had contact with health care services in the year before
      death of the case subject (p = 0.03), even when psychiatric diagnoses were
      controlled for in conditional regression analysis (OR 1.02 [95% CI 1.01-1.04] and
      5.0 [95% CI 1.07-23.7] respectively). INTERPRETATION: Since case subjects had
      frequent contact with health care services, frontline medical personnel may be in
      a position to identify people at risk for suicide.

PMID- 11584563
TI  - Outcomes and costs of coronary artery bypass grafting: comparison between
      octogenarians and septuagenarians at a tertiary care centre.
AB  - BACKGROUND: Decision-making related to coronary artery bypass grafting (CABG) in
      elderly patients is hampered by inadequate outcome data. We compared the clinical
      outcomes of octogenarians with those of septuagenarians who underwent CABG. Our
      secondary objective was to compare the costs associated with CABG in these
      groups. METHODS: We conducted a retrospective database review of patients 70
      years of age and older who had undergone CABG at a regional cardiac surgical
      centre in Hamilton, Ont., between July 1, 1997, and Apr. 30, 2000. A total of
      1034 patients were divided into 3 age groups: young septuagenarians (aged 70-74
      years), old septuagenarians (aged 75-79) and those 80 and older. Costs were
      determined in a subset of 773 patients with the use of a case-costing system for
      cardiac surgery developed at our institution. RESULTS: The 3 groups were similar
      with respect to sex distribution and preoperative risk factors. Urgency scores at
      referral differed significantly between the groups, with the young
      septuagenarians demonstrating the lowest risk (mean score [and standard
      deviation] 4.48 [1.3] in that group, 4.28 [1.4] in the old septuagenarian group
      and 4.11 [1.2] in the octogenarian group). The rates of all complications
      combined were similar between the 3 groups (27.1%, 28.1% and 29.6% in the young
      and old septuagenarian groups and the octogenarian group respectively). There
      were no significant differences between the 3 groups in the mean number of grafts
      per patient (3.0, 3.1 and 3.0 respectively), the rate of postoperative death
      (3.3%, 5.7% and 4.2%), the mean length of stay (11.7, 13.4 and 12.6 days) or the
      incidence of postoperative myocardial infarction (4.5%, 3.4% and 4.2%). The total
      cost of CABG per patient did not differ significantly between the 3 groups.
      INTERPRETATION: Given that patients who are accepted for CABG represent a
      selected population, our findings suggest that, with careful triage, CABG in
      octogenarians is as safe as, and no more costly than, CABG in septuagenarians.

PMID- 11584564
TI  - Assessing telemedicine: a systematic review of the literature.
AB  - BACKGROUND: To clarify the current status of telemedicine, we carried out a
      systematic review of the literature. We identified controlled assessment studies
      of telemedicine that reported patient outcomes, administrative changes or
      economic assessments and assessed the quality of that literature. METHODS: We
      carried out a systematic electronic search for articles published from 1966 to
      early 2000 using the MEDLINE (1966-April 2000), HEALTHSTAR (1975-January 2000),
      EMBASE (1988-February 2000) and CINALH (1982-January 2000) databases. In
      addition, the HSTAT database (Health Services/Technology Assessment Text, US
      National Library of Medicine), the Database of Abstracts of Reviews of
      Effectiveness (DARE, NHS Centre for Reviews and Dissemination, United Kingdom),
      the NHS Economic Evaluation Database and the Cochrane Controlled Trials Register
      were searched. We consulted experts in the field and did a manual search of the
      reference lists of review articles. RESULTS: A total of 1124 studies were
      identified. Based on a review of the abstracts, 133 full-text articles were
      obtained for closer inspection. Of these, 50 were deemed to represent assessment
      studies fulfilling the inclusion criteria of the review. Thirty-four of the
      articles assessed at least some clinical outcomes; the remaining 16 were mainly
      economic analyses. Most of the available literature referred only to pilot
      projects and short-term outcomes, and most of the studies were of low quality.
      Relatively convincing evidence of effectiveness was found only for teleradiology,
      teleneurosurgery, telepsychiatry, transmission of echocardiographic images, and
      the use of electronic referrals enabling e-mail consultations and video
      conferencing between primary and secondary health care providers. Economic
      analyses suggested that teleradiology, especially transmission of CT images, can
      be cost-saving. INTERPRETATION: Evidence regarding the effectiveness or cost
      effectiveness of telemedicine is still limited. Based on current scientific
      evidence, only a few telemedicine applications can be recommended for broader
      use.

PMID- 11584565
TI  - Evidence or faith? Coronary artery bypass grafting in elderly patients.

PMID- 11584566
TI  - Information technology and telemedicine.

PMID- 11584567
TI  - Telemedicine in Africa: potential, problems, priorities.

PMID- 11584568
TI  - The modern scientific physician: 3. Scientific diagnosis.

PMID- 11584569
TI  - Dancing with the porcupine: rules for governing the university-industry
      relationship.

PMID- 11584570
TI  - Sponsorship, authorship and accountability.

PMID- 11584572
TI  - AIDS: after 20 years, complacency.

PMID- 11584571
TI  - New advances in the management of acute coronary syndromes: 2. Fibrinolytic
      therapy for acute ST-segment elevation myocardial infarction.

PMID- 11584573
TI  - School's back, and so is the lowly louse.

PMID- 11584574
TI  - Paracrine function of cultured aortic endothelial cells in spontaneously
      hypertensive rats.
AB  - BACKGROUND: Vasoconstrictor and vasodilator release from vascular endothelial
      cells not only regulates vascular tone but also induces vascular smooth muscle
      cell proliferation. METHODS: In order to understand the role of vasoconstrictor
      and vasodilator release in the development of hypertension in spontaneously
      hypertensive rats (SHR), aortic endothelial cells were isolated and cultured from
      4-week-old and 24-week-old SHR (SHR-4 and SHR-24) and age-matched Wistar-Kyoto
      rats (WKY-4 and WKY-24) used as control. Prostacyclin (PGI2), endothelin-1 (ET-1)
      and thromboxane A2 (TXA2) release from cultured endothelial cells in the culture
      medium, were measured after 30 min with or without treatment with acetylcholine,
      calcium ionophore A23187 or thrombin. RESULTS: The results showed that there was
      no significant difference in ET-1 secretion between SHR-4 and age-matched WKY
      rats, but ET-1 secretion was about twice as high in SHR-24 as in WKY-24. TXA2
      secretion was significantly higher in SHR-4 than in WKY-4 and was also higher
      than in SHR-24, but there was no significant difference between SHR-24 and WKY
      24. The secretion of PGI2 was higher in SHR-24 than in WKY-24 and also higher
      than in SHR-4 and WKY-4. The prostaglandin PGI2 and TXB2 secretions from all
      groups of cultured VECs treated with various reagents, acetylcholine, calcium
      ionophore A23187 or thrombin were increased in similar patterns. However, there
      was no significantly different response between SHR and WKY VECs. CONCLUSIONS:
      Similar levels of ET-1 secreted from endothelial cells between SHR-4 and WKY-4
      indicated that ET-1 secretion seems not a crucial factor in early hypertension
      development in SHR. The high level of TXA2 secretion in SHR-4 may involve in
      early hypertension development in SHR.

PMID- 11584575
TI  - The in vitro inhibitory effect of flavonoid astilbin on 3-hydroxy-3
      methylglutaryl coenzyme A  reductase on Vero cells.
AB  - BACKGROUND: Epidemiological studies have shown that hypercholesterolemia is a
      major risk factor for coronary heart disease. In clinical trials of lipid
      lowering therapy, 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase
      inhibitor has been shown to decrease cardiac events and mortality. Flavonoids are
      polyphenolic natural antioxidants existing in vegetables, fruits and beverages
      such as tea and wine. Previous studies have shown that some antioxidants had
      hypocholesterolemic effect, and flavonoid intake was associated with the decrease
      of mortality from coronary artery disease. The aim of this study was to evaluate
      the inhibitory effect of flavonoids on HMG-CoA reductase. METHODS: The methods
      for analysis of specific inhibitors of mevalonate biosynthesis have been well
      established, using Vero cells, a cell line obtained from kidneys of African green
      monkeys. Flavonoids isolated from different traditional Chinese herbs were
      dissolved in DMSO and incubated with Vero cells with or without the addition of 1
      mM mevalonate or 5 mM sodium acetate in order to observe cell growth for 24 h.
      RESULTS: Concentrations of 1 mM mevalonate or 5 mM sodium acetate were added into
      culture medium in order to observe the effect on cell growth. Different
      concentrations of pravastatin to inhibit cell growth were used as a positive
      control. About 40 flavonoid compounds were used for study, only one compound,
      astilbin (belonging to the flavonol group), showed significant inhibition of Vero
      cell growth. CONCLUSIONS: This study shows that one flavonoid compound, isolated
      from traditional medicinal herbs, may be an effective HMG-CoA reductase inhibitor
      which might be developed into a new hypocholesterolemic agent.

PMID- 11584576
TI  - Six months follow-up of patients with methamphetamine psychosis.
AB  - BACKGROUND: It has been nearly 50 years since the psychotic state caused by
      amphetamine was first reported. However, the prognosis of methamphetamine (MAP)
      psychosis and its relationship with chronic schizophrenia are still vague. Some
      authors preferred MAP psychosis model of schizophrenia, while other studies found
      difference between the two groups of patients in the aspects of negative
      symptoms. METHODS: In this study we followed 21 psychiatric inpatients with
      diagnosis of MAP psychosis. Schedule for affective disorders and schizophrenia
      (SADS), scale for assessment of negative symptoms (SANS) and global assessment
      scale (GAS) were used for evaluation of these patients during admission and six
      months after discharge. RESULTS: Seventeen patients were interviewed and eight of
      them confessed reuse of MAP. The follow-up examinations found decreased total
      scores of delusion and hallucination in SADS and increased GAS scores. The SANS
      scores of the MAP psychotic patients in this study were lower than moderate
      level. No significant change could be found for most SANS subcategory scores
      except some items. CONCLUSIONS: Most MAP psychotic patients followed in this
      study improved much in six months. The results of the SANS evaluation and the
      clinical course for six months indicated that the MAP psychosis is a psychotic
      disorder different from chronic schizophrenia.

PMID- 11584577
TI  - Autologous peripheral blood stem cell transplantation for patients with
      malignancies: the Tri-Service General Hospital experience.
AB  - BACKGROUND: High-dose chemotherapy/radiotherapy followed by autologous peripheral
      blood stem cells transplantation (APBSCT) can be used to treat chemosensitive
      malignant diseases. We retrospectively studied the APBSCT treatment efficacy and
      safety of patients at Tri-Service General Hospital (TSGH). METHODS: From January
      1994 to March 2000, 11 patients were treated with high doses of
      chemotherapy/radiotherapy followed by APBSCT. Nine patients were male and 2 were
      female. The median age was 26 years, with a range of 21 to 51. There were 7 acute
      myeloid leukemia (AML), 3 non-Hodgkin's lymphoma (NHL) and 1 ovarian cancer. All
      patients received both chemotherapy and granulocyte-colony stimulating factor to
      mobilize hematopoietic stem cells, and the most commonly used conditioning
      regimen was combined chemotherapy with Busulfan and Cyclophosphamide. RESULTS:
      The median numbers of infused mononuclear and CD34+ cells were 3.19 x 10(8)/kg
      and 9.2 x 10(6)/kg, respectively. Nine of the 11 patients engrafted successfully,
      but 2 patients with AML failed to engraft. The median times of WBC recovery (ANC
      > or = 500/uL) and platelet recovery (> or = 20 x 10(3)/uL) were 13 and 16 days,
      respectively. Four patients with AML survived after APBSCT and two of them were
      alive and disease-free for 36 and 51 months, respectively. One patient with AML
      and 3 patients with NHL died of relapse, and one patient with ovarian cancer was
      alive but with disease at 50 months. CONCLUSIONS: For patients with AML, APBSCT
      may be an alternative, safe and useful treatment modality. Further strategies for
      reducing relapse in lymphoma patients merit further investigation.

PMID- 11584578
TI  - Pulmonary function during exercise in obese children.
AB  - BACKGROUND: Obesity imposes additional stress to ventilation during exercise. The
      purpose of this study is to evaluate the pulmonary function changes with graded
      exercise and the habitual level of physical activity in obese children. METHODS:
      This study recruited 42 obese and 10 normal students, aged 11, from Tamsui
      Elementary School. Measurements of cardiopulmonary fitness were recorded after a
      jump rope test. Height, weight and body mass indices were determined before
      testing. RESULTS: A significant correlation was found between triceps skin-fold
      thickness and the body mass index (BMI; r = 0.65, p < 0.05). Blood systolic
      pressure significantly increased in the obese subjects in their post-exercise
      test. There was no significant difference between the obese and the non-obese
      groups in any of the lung function test measurements. Forced expiratory volume in
      the first second (FEV1), peak expiratory flow rate (PEFR) and forced vital
      capacity (FVC) were similar in both groups. CONCLUSIONS: Physiologic responses
      are not sufficiently different from between the obese subjects and the non-obese
      children. We should pay more attention to fostering confidence in the obese child
      exercise.

PMID- 11584579
TI  - Non-penetrating trabeculectomy for open angle glaucoma.
AB  - BACKGROUND: Non-penetrating trabeculectomy is used as the surgical intervention
      for open angle glaucoma. It has advantage of creating gradual filtration through
      the thin trabeculo-Descemet membrane to reduce markedly the postoperative
      complications typical for penetrating operation. We described our experience of
      the non-penetrating trabeculectomy for open angle glaucoma. METHODS: This is a
      retrospective study of 28 eyes of 28 patients with primary open glaucoma (POAG).
      Non-penetrating trabeculectomy was performed by one surgeon from July 1998 to
      March 2000. Examinations were performed preoperatively and postoperatively in 1
      and 7 days and 1, 3, 6, 12 and 21 months. RESULTS: The mean follow-up was 12.5 +/
      6.3 months (S.D.). The mean preoperative intraocular pressure (IOP) was 27.8 +/-
      6.7 mmHg. The mean postoperative IOP was 11.5 +/- 6.2 mmHg in 1 day and 15.7 +/-
      5.8 mmHg in 1 week, and it remained stable in the following 12 months. IOP of
      71.3% (20/28) of the eyes could be controlled below or equal to 21 mmHg with no
      or only topical antiglaucoma medication. There were only few postoperative
      complications. CONCLUSIONS: Non-penetrating trabeculectomy is efficient in
      controlling intraocular pressure of open angle glaucoma. No entering the anterior
      chamber diminishes the postoperative complications typical of the penetrating
      trabeculectomy.

PMID- 11584580
TI  - A metastatic pituitary carcinoid tumor successfully treated with gamma knife
      radiosurgery.
AB  - Intracranial metastasis occurs in a certain number of patients with carcinoid
      tumor. However, carcinoid tumor with metastasis to the pituitary gland is
      extremely rare. Up to the present, no effective treatment for either a metastatic
      intracranial carcinoid tumor or a metastatic pituitary lesion of any origin has
      been documented. We have treated a case of metastatic carcinoid tumor of the
      pituitary gland with transsphenoidal tumor resection followed by gamma knife
      radiosurgery. A 59-year-old man presented with headache and left oculomotor
      palsy. He was treated at the same hospital for bronchial atypical carcinoid tumor
      one and a half years ago. Magnetic resonance image of the brain showed a
      pituitary tumor. There were no signs of recurrent or metastatic lesion elsewhere
      despite thorough investigation. Transsphenoidal approach for removal of tumor was
      done and the pathology turned out to be a metastatic carcinoid tumor. Subsequent
      gamma knife radiosurgery was given for residual tumor. The oculomotor palsy
      improved after radiosurgery. No neurological deficit occurred. Follow-up CT scan
      of the brain showed complete resolution of the tumor. We concluded that gamma
      knife radiosurgery could be used to treat a metastatic intracranial carcinoid
      tumor. It can also be used to treat a metastatic lesion of the pituitary gland
      without causing neurological deficit.

PMID- 11584581
TI  - Fibrillary glomerulonephritis.
AB  - The occurrence of fibrillary glomerulonephritis is unusual in Taiwan, whereas it
      occurs in approximately 1% of renal biopsy specimens taken in the United States
      of American. This disease is characterized by extracellular randomly arranged non
      branching Congo red-negative microfibrils within glomeruli. The microfibrils are
      less than 30 nm in diameter, and electron microscopy is essential for diagnosis.
      Differential diagnosis of the deposition of extracellular non-branching
      microfibrils within glomeruli is important because discrete diseases have
      different therapeutic and prognostic implications. The report will discuss two
      cases of biopsy-proved fibrillary glomerulonephritis who presented with
      proteinuria, hematuria, renal insufficiency, and hypertension. It is noteworthy
      that the renal function persistently went downhill, even though the physician
      treated the patients with corticosteroids, pulse treatment and immunosuppressive
      agents.

PMID- 11584582
TI  - Bone-fracture risk in a wheelchair user.

PMID- 11584583
TI  - Key developments in geriatric medicine.

PMID- 11584584
TI  - Depression: a common but treatable disorder.

PMID- 11584585
TI  - Prescribing for the elderly: a GP guide.

PMID- 11584586
TI  - The diagnosis of Paget's disease.

PMID- 11584587
TI  - Diagnosing and treating atypical pneumonia.

PMID- 11584588
TI  - Managing patients with diabetic neuropathy.

PMID- 11584589
TI  - Foot problems seen in children.

PMID- 11584590
TI  - Constipation in infants and children.

PMID- 11584592
TI  - Stimulate the phagocytes.

PMID- 11584591
TI  - How to be an excellent GP.

PMID- 11584594
TI  - Promoter analysis in mycobacteria using xyIE reporter assays and its implication
      in high throughput screening.
AB  - Understanding the molecular biology of Mycobacterium tuberculosis has become the
      focus of recent studies in infectious diseases. Here, we describe a
      spectrophotometric method for quantitative analysis of promoters in mycobacteria.
      The assay is a modification of the xyIE reporter assay, which uses an inexpensive
      substrate, catechol. The distinguishing feature of this protocol is that cells
      are grown by patching on agar plates, and directly used in the assays. The
      absorption measurements of the cell suspension at 375 nm in the presence and
      absence of the substrate are used for obtaining xyIE activity and for
      normalization of the assay values respectively. These features make the assay
      system directly amenable for high throughput analyses.

PMID- 11584593
TI  - Mycolic acids and ancient DNA confirm an osteological diagnosis of tuberculosis.
AB  - SETTING: The underlying trends in the past epidemiology of tuberculosis (TB) are
      obscure, requiring recourse to the archaeological record. It would therefore be
      of value to develop methods for reliable TB diagnosis in ancient populations.
      OBJECTIVE: To test the capability of two biomarkers, Mycobacterium tuberculosis
      complex mycolic acids and a DNA target (IS6110), for confirming an osteological
      diagnosis of TB in medieval individuals, based on the presence of Pott's disease
      and/or rib lesions. DESIGN: Osteological examination of three archaeological
      individuals (Medieval: approximately 1000 years old) revealed a Pott's disease
      case, one with no changes consistent with TB and one with rib lesions. Rib
      samples from these individuals were examined for the presence of Mycobacterium
      tuberculosis complex mycolic acids and mycobacterial DNA. RESULTS: Mycobacterium
      tuberculosis complex mycolic acids and the DNA target were detected in the Pott's
      disease case, whilst mycolic acids (insufficient for confirmation) alone were
      detected in the rib lesion case. CONCLUSIONS: Biomarkers provide a sensitive tool
      to detect ancient TB. Mycobacterium tuberculosis DNA is not distributed
      homogeneously, making multiple sampling essential. Mycolic acids seem more
      reliable for ancient TB diagnosis than IS6110. The demonstrated stability of
      mycolic acids show that they may be of value in tracing the palaeoepidemiology of
      tuberculosis back into antiquity.

PMID- 11584595
TI  - Detection of Mycobacterium tuberculosis in clinical samples using insertion
      sequences IS6110 and IS990.
AB  - To detect Mycobacterium tuberculosis in clinical samples, we used the M.
      tuberculosis-complex specific insertion sequence IS990 as the target in a simple
      DIG-PCR ELISA assay, as this element is present as a single copy in all strains
      of M. tuberculosis we have examined to date. The IS990 test was compared with a
      similar PCR that utilizes IS6110 as target. For detection of PCR product,
      digoxigenin-11-dUTP (DIG-dUTP) was incorporated into the product. After
      amplification, the PCR product was hybridized with biotinylated capture probe,
      which was complementary to the inner part of the amplicon. The hybrid was
      captured onto streptavidin-coated microtiter plate and DIG-labeled PCR product
      was detected using a peroxidase-conjugated antibody to DIG. We evaluated DIG-PCR
      ELISA for the detection of M. tuberculosis DNA in 265 respiratory and non
      respiratory specimens taken from patients with known and suspected tuberculosis
      disease or from controls. The sensitivity and specificity of both IS990-based
      test and IS6110-based test was 96.5% and 95.3% respectively, comparable to the
      sensitivity and specificity of the IS6110-based test. The results demonstrate
      that the IS990 PCR ELISA test is a rapid and sensitive tool for the detection and
      identification of M. tuberculosis in clinical samples, and may have advantages to
      the more widely used IS6110-based tests, particularly in areas where IS6110
      negative strains are found.

PMID- 11584596
TI  - Growth phase-associated changes in protein expression in Mycobacterium smegmatis
      identify a new low molecular weight heat shock protein.
AB  - De novo protein synthesis and the heat-shock response during different stages of
      bacterial culture of Mycobacterium smegmatis LR222 were investigated. A
      discontinuance in the increase in number of colony forming units occurred at mid
      exponential phase of growth. This coincided with a plateau in the ATP content of
      the culture, a reduction in the synthesis of exponential phase proteins (58,
      30.5, and 20 kDa), a transitory synthesis of a 32 kDa protein and the induction
      of stationary-phase proteins (48, 46, 31, 25, and 20 kDa). The response to heat
      shock showed a growth-phase dependency, with the highest fold-induction of the 75
      kDa (DnaK) protein occurring during the transitory cessation in the increase in
      CFU, while the greatest increase of the 95 kDa, 66 kDa (GroEL), and approximately
      17 kDa (a doublet) proteins occurred during stationary phase. The approximately
      17 kDa doublet was resolved into four polypeptides by two-dimensional
      electrophoresis. Mass spectrometric analysis of the sequence of one polypeptide
      (named Hsp17-2, 16.8 kDa) revealed significant homology to a conserved, 16.2 kDa,
      hypothetical protein of unknown function in Mycobacterium tuberculosis H37Rv. The
      increased synthesis of Hsp17-2 in response to heat shock suggests that it may
      represent a new low molecular weight heat shock protein.

PMID- 11584598
TI  - The challenges of medical illustrators. An orthopaedic surgeon's view.

PMID- 11584597
TI  - Molecular evolution of Mycobacterium tuberculosis: phylogenetic reconstruction of
      clonal expansion.
AB  - SETTING: M. tuberculosis isolates were collected from patients attending health
      clinics in a high incidence urban community and in a low incidence rural setting
      in South Africa. OBJECTIVE: To reconstruct the evolutionary history of a group of
      closely related M. tuberculosis isolates using IS6110, DRr and MTB484(1)
      restriction fragment length polymorphism (RFLP) data. DESIGN: Mycobacterium
      tuberculosis isolates containing an average of ten IS6110 elements, with a
      similarity index of > or = 65% were genotypically classified by DNA
      fingerprinting using the IS6110 derived probes IS-3' and IS-5', as well as the
      DRr and MTB484(1) probes, in combination with PvuII or Hinfl endonuclease
      digestion. These RFLP data were subjected to phylogenetic analysis using both
      genetic distance and parsimony algorithms. RESULTS: Phylogenetic analysis
      predicted the existence of two independently evolving lineages, possibly evolving
      from a common ancestral strain. The topology of the phylogenetic tree was
      supported by comprehensive bootstrapping and the specific partitioning of DNA
      methylation phenotypes. The observed difference in the branch lengths of the two
      lineages may suggest differential evolutionary rates. Isolates collected from
      different geographical regions demonstrate independent evolution, suggesting that
      it is highly unlikely that strains have been recently transmitted between the two
      regions. The number of evolutionary events identified in this strain family
      differs significantly from that of previously characterized strain families,
      implying that evolutionary rate may be strain family dependent. CONCLUSION: Based
      on this analysis we propose that the algorithm used to calculate recent
      epidemiological events should be revised to incorporate the evolutionary
      characteristics of individual strain families, thereby enhancing the accuracy of
      molecular epidemiological calculations.

PMID- 11584599
TI  - An evaluation and comparison of three digital image databases.
AB  - Both the Western Infirmary and Gartnavel General Hospital's Medical Illustration
      Departments have been using digital cameras since 1998. This has led to a
      dramatic increase in the number of digital images held on the department's
      computers. As all digital files were named with a job number, consultant and
      department, searches carried out using other parameters was labour intensive. A
      new system of defining and organizing digital images across both departments was
      needed. This system needed to be efficient, flexible and easy to use. Choosing
      the right software was vital and it was decided that the only way to make an
      informed decision would be to test the three best software products to see how
      they compared.

PMID- 11584600
TI  - Online publishing: how, why and other related issues.
AB  - The Internet allows the creation of a peer reviewed online journal, such as
      Images in Paediatric Cardiology, at a fraction of the cost of a conventional
      journal. Furthermore, an online journal can display a multitude of images and
      other multimedia material (such as audio and video files)--a feature not
      available in a conventional journal. The issues of creating such a journal are
      explored, along with the issues of online publishing, including copyright and
      peer review. Current proposals that may affect copyright and peer review in all
      journals are also outlined.

PMID- 11584601
TI  - Hirudo medicinalis: the medicinal leech.

PMID- 11584602
TI  - Albinism and melanocytes.

PMID- 11584603
TI  - Digital imaging: a viable alternative to conventional medico-legal photography?

PMID- 11584604
TI  - Adobe Photoshop and Illustrator techniques.

PMID- 11584605
TI  - The Macewen collection of clinical photographs (Circa 1880-1918).

PMID- 11584607
TI  - Violence on psychiatrists: preventing future increases.

PMID- 11584606
TI  - Alice Gretener, 1905-1986, medical artist, moulage maker & wax modeller.

PMID- 11584608
TI  - The future of education: Workforce and Development Confederations.

PMID- 11584609
TI  - The aetiology and epidemiology of faecal incontinence.
AB  - Faecal incontinence is experienced by at least 2% of the population and 7% of
      those over 65 years of age. The true incidence is probably much higher because of
      the stigmata of the affliction leading to underreporting. The common causes of
      faecal incontinence are discussed.

PMID- 11584610
TI  - Investigation of faecal incontinence.
AB  - Most patients with faecal incontinence require only a full history (information
      about other predisposing causes) and examination (assessment for faecal impaction
      and evaluation of sphincter function and structure). When necessary, anorectal
      physiological studies, endoanal ultrasound and magnetic resonance imaging allow
      accurate characterization of sphincter function and structure.

PMID- 11584611
TI  - Non-surgical management of faecal incontinence.
AB  - Faecal incontinence is a common symptom causing reduction in quality of life and
      social isolation. Conservative treatments should be used as first and second
      lines of therapy and can also be of use as adjuncts to surgical treatment. This
      article reviews the current status of these modalities of treatment.

PMID- 11584612
TI  - The surgical management of faecal incontinence.
AB  - The surgical management of faecal incontinence is complex and technically
      demanding. Surgery should only be offered once the aetiology has been correctly
      identified and the patient has been counselled regarding outcomes of success.
      This may only approach 80%, with long-term results declining with time.

PMID- 11584614
TI  - Managing schizophrenia: an update.
AB  - Atypical antipsychotic drugs offer hope to schizophrenics and their families.
      Controversy continues over their cost-effectiveness but patient surveys suggest
      increased compliance and thus improved mental health. This article reviews
      schizophrenia management, exploring the consequences of failing to adopt modern
      therapies in hampering compliance and stigmatizing the mentally ill.

PMID- 11584613
TI  - Recent developments in the treatment of faecal incontinence.
AB  - Many patients with faecal incontinence can be cured using a simple anal sphincter
      repair. Some patients are unsuitable for this either because the sphincter is
      absent, too extensively damaged or anal sphincter repair has failed. In these
      patients novel treatments have been introduced to augment, replace and stimulate
      the anal sphincter.

PMID- 11584615
TI  - Improving the management of chronic myeloid leukaemia.
AB  - Until recently the therapeutic options available to patients diagnosed with
      chronic myeloid leukaemia hinged on their suitability for allogeneic bone marrow
      transplantation. With the advent of new agents targeting the specific molecular
      pathways involved in the disease, drug therapies may have an increasingly
      important role in improving outcome.

PMID- 11584616
TI  - Lessons from the Bristol Inquiry for education and training in the NHS.
AB  - The vast body of evidence, analysis and judgment within the Bristol Inquiry
      report gives rise to a host of recommendations for change. Most are relevant to
      health systems everywhere and to all parts of those health systems. Some raise
      issues which cry out to be addressed within the education, training and
      development of all health professionals.

PMID- 11584617
TI  - Managing postoperative pain.
AB  - The postoperative course of a patient can be complicated by events such as pain,
      nausea and vomiting. These in themselves can have a significant impact upon
      morbidity and even survival. This article outlines key points to minimize such
      adverse outcomes.

PMID- 11584618
TI  - Percutaneous balloon mitral valvuloplasty.
AB  - Mitral stenosis is commonly encountered in the elderly and among immigrant
      communities. Percutaneous balloon mitral valvuloplasty provides effective
      treatment. The present article provides a brief overview of the principles of
      patient selection, technical details of the procedure itself and information
      concerning complications and follow-up.

PMID- 11584619
TI  - Electrocardiogram interpretation. Case 6: transient ST elevation.

PMID- 11584620
TI  - Writing your curriculum vitae.
AB  - Your curriculum vitae (CV) is your gateway to shortlisting. A good CV takes a
      long time to prepare. It should not only record your training but, more
      importantly, should reflect your 'physicianly' qualities, management skills and
      knowledge of health-care systems.

PMID- 11584621
TI  - Spinal epidural haematoma misdiagnosed as meningitis.

PMID- 11584622
TI  - Increasing breathlessness, hyperkalaemia and thrombocytosis in a patient with
      chronic obstructive pulmonary disease.

PMID- 11584624
TI  - Images in medicine. Large airway involvement in relapsing polychondritis.

PMID- 11584625
TI  - Preoxygenation to improve patient safety.

PMID- 11584626
TI  - Airline travel and DVT: a cautionary tale.

PMID- 11584627
TI  - Nutritional support in acute pancreatitis: the enteral vs parenteral dilemma.

PMID- 11584628
TI  - Influence of illegal gold mining on mercury levels in fish of north Sulawesi's
      Minahasa Peninsula, (Indonesia).
AB  - North Sulawesi's Minahasa Peninsula currently is experiencing intense illegal
      gold mining activity. It has been estimated that 200 t of mercury are used
      annually in Indonesia in the recovery of gold from the illegal mines. To date no
      study has assessed the environmental impact of this illegal activity on the
      nearby aquatic biota. To address this concern, we compared tissue mercury levels
      from several sites, including a reference site and a site near an illegal mine.
      Fish from the region of the illegal mine contained 30 times the mercury content
      of fish at the reference site. Moreover, whole fish tissue levels were four times
      those recommended by the World Health Organization for consumption restrictions
      and often two-fold higher than recommended for total restriction on fish
      consumption. The environmental and human health implications of these levels are
      of grave concern; citizen education programmes are required to alert indigenous
      peoples of the risks associated with mercury exposure and fish consumption
      guidelines put into place. A more comprehensive effort to identify major sources
      and effects are required. Such information can be used to determine the correct
      course of action that needs to be taken to close existing illegal mines and
      prevent future illegal mining activities.

PMID- 11584629
TI  - Interspecific variation in heavy metal body concentrations in Hong Kong marine
      invertebrates.
AB  - Accumulated body concentrations of cadmium, copper and zinc were investigated in
      19 species of intertidal invertebrates (the barnacles Tetraclita squamosa,
      Capitulum mitella, Balanus amphitrite, Megabalanus volcano, the bivalves
      Saccostrea cucullata, Septifer virgatus and Brachidontes atratus, the chiton
      Acanthopleura japonica and the gastropods Cellana grata, Cellana toreuma,
      Patelloida saccharina, Patelloida pygmaea, Siphonaria japonica, Tegula
      argyrostoma, Lunella coronata, Monodonta labio, Nerita albicilla, Thais clavigera
      and Thais luteostoma) collected from a relatively unpolluted area in Hong Kong,
      i.e. two shores within the Cape d'Aguilar Marine Reserve. In general body metal
      concentrations could be explained by the accumulation strategy of the analysed
      organism and by physiological requirements for the essential metals, i.e. copper
      and zinc. Zinc concentrations were, therefore, greatest in the barnacles and the
      oyster S. cucullata. Copper concentrations were greatest in those gastropods
      containing the respiratory pigment haemocyanin and in S. cucullata. One species
      collected from the sheltered shore, i.e. T. luteostoma, had much higher copper
      body concentrations compared with exposed shore conspecifics and this may be
      attributed to a diet that was dominated by oysters, which have high copper body
      concentrations. In contrast to both copper and zinc, cadmium body concentrations
      showed little interspecific variation.

PMID- 11584630
TI  - Multivariate statistical and GIS-based approach to identify heavy metal sources
      in soils.
AB  - The knowledge of the regional variability, the background values and the
      anthropic vs. natural origin for potentially harmful elements in soils is of
      critical importance to assess human impact and to fix guide values and quality
      standards. The present study was undertaken as a preliminary survey on soil
      contamination on a regional scale in Piemonte (NW Italy). The aims of the study
      were: (1) to determine average regional concentrations of some heavy metals (Cr,
      Co, Ni, Cu, Zn, Pb); (2) to find out their large-scale variability; (3) to define
      their natural or artificial origin; and (4) to identify possible non-point
      sources of contamination. Multivariate statistic approaches (Principal Component
      Analysis and Cluster Analysis) were adopted for data treatment, allowing the
      identification of three main factors controlling the heavy metal variability in
      cultivated soils. Geostatistics were used to construct regional distribution
      maps, to be compared with the geographical, geologic and land use regional
      database using GIS software. This approach, evidencing spatial relationships,
      proved very useful to the confirmation and refinement of geochemical
      interpretations of the statistical output. Cr, Co and Ni were associated with and
      controlled by parent rocks, whereas Cu together with Zn, and Pb alone were
      controlled by anthropic activities. The study indicates that background values
      and realistic mandatory guidelines are impossible to fix without an extensive
      data collection and without a correct geochemical interpretation of the data.

PMID- 11584631
TI  - Biochemical changes in needles of Pinus radiata D. Don trees in relationship to
      long-term ozone exposure indices.
AB  - Ambient concentrations of ozone in Europe are high enough to cause negative
      effects on vegetation. Therefore, many efforts have been made to determine
      exposure indices and critical levels for protection of vegetation. In this
      context, the choice of a suitable attribute to determine the pollutant effect is
      of paramount importance. Until now, much of the work has been done with
      attributes such as biomass or growth. In the present work correlation factors
      have been established between biochemical parameters (peroxidase activity,
      ascorbate and sulfhydryl contents) of Pinus radiata trees and exposure indices of
      ozone. Our results show that peroxidase cannot be used as an indicator of effects
      of long-term exposure to ozone but still remains as an excellent indicator of
      short-term ozone fluctuations in the field. Ascorbate may act as an intermediate
      indicator responding to both short fluctuations and long-term exposures to ozone.
      Finally, sulfhydryl may be used as a long-term indicator in relation to the AOT
      (average over threshold) exposure index. Our results also point to the fact that
      Pinus radiata may be affected by ozone at AOT values lower than 10 ppm.h as
      already observed with other tree species.

PMID- 11584632
TI  - Intraspecific competition in populations of Helix aspersa with different
      histories of exposure to lead.
AB  - A range of invertebrates have become adapted to certain toxic metals, such that,
      in the presence of the contaminant, some measure of their performance, typically
      growth or reproduction, is superior to that of an unexposed population. Under
      such a toxic stress, a population with a history of exposure might outperform a
      naive population in competition for limited resources. This study compared the
      shell growth of laboratory-bred juveniles from six populations of Helix aspersa
      with different histories of exposure to Pb. In 10 trials using various
      combinations of two populations, the snails competed for a limited supply of food
      that contained either no Pb or 500 micrograms/g-1 Pb, for 98 days. Each trial
      consisted of 10 juveniles, five from each population and was replicated four
      times. Nearly all of the food provided was consumed quickly after presentation.
      The total amount of shell growth within each replicate (the sum of the mean
      growth of the two populations) was highly consistent between trials so that the
      total amount of shell built was limited by food availability. The presence of Pb
      in the diet caused no measurable depression of shell growth and exposure history
      did not appear to confer any competitive advantage or disadvantage in any of the
      trials. One population consistently grew faster than its competitors in every
      trial of which it was a part. Shell growth tended to be greater in smaller
      juveniles. Snail activity is known to be inhibited at high densities and this may
      have contributed to the lower incremental growth in individuals kept at the
      higher densities. The competitive advantage enjoyed by one population may be
      primarily determined by their activity or perhaps their Ca metabolism.

PMID- 11584633
TI  - Rare earth elements in naturally grown fern Dicranopteris linearis in relation to
      their variation in soils in south-Jiangxi region (southern China).
AB  - Ferns (Dicranopteris linearis) and soils, sampled from four rare earth mining
      areas and one non-mining area locating in South-Jiangxi region, were chosen for
      analysis of 15 rare earth elements (REEs) by inductively coupled plasma-mass
      spectrometry (ICP-MS). The fern samples were divided into 4 parts: root, stem,
      petiole, and lamina. The soils of the same sites were also sampled, and 4 soil
      layers were observed at the profile: A (0-20 cm depth), B (20-150 cm depth), C
      (150-400 cm depth), and D (rock). The distribution patterns and transportation
      characteristics of REEs of different soil layers and of different parts of D.
      linearis were studied. The results showed that in the soil layers, the sigma REE
      (the sum of the concentrations of 15 REEs) of A layer, as well as B layer were
      lower than that of C layer, but Ce was relatively concentrated in A layer. The
      sigma REE of different parts of D. linearis were lamina, root > stem > petiole.
      The REE distribution patterns of D. linearis root were similar to the total REE
      distribution patterns of the A layer of their host soils, especially to the
      soluble REE distribution patterns of the A layer of their host soils. The REEs
      were fractionated in their transportation in D. linearis. The abundances of heavy
      rare earth elements (HREEs, Gd to Lu and Y) in the stem, petiole, lamina are
      lower than those in the root.

PMID- 11584634
TI  - Selected trace metals in oysters (Crassostrea iridescens) and sediments from the
      discharge zone of the submarine sewage outfall in Mazatlan Bay (southeast Gulf of
      California): chemical fractions and bioaccumulation factors.
AB  - Concentrations of Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn in the soft tissue of
      Crassostrea iridescens and the associated surface sediments (bulk and
      bioavailable metal concentrations) from an area influenced by a sewage outfall in
      Mazatlan Bay (southeast Gulf of California), were determined by atomic absorption
      spectrophotometry. Significant spatial differences in metal concentrations in
      both the bulk and bioavailable forms in the sediments were identified. An
      enrichment of Cu, Ni, Pb and Zn in sites located on a south-north transect was
      detected indicating a dominant influence of the sewage outfall toward the north.
      C. iridescens accumulated more Zn, Cu, Ni, Fe, Cd; and less Mn, Cr and Pb than
      were bioavailable in the sediments, as measured using conventional extraction
      analysis. The degree of enrichment and the bioavailable metal concentrations in
      the sediments of the south portion of Mazatlan Bay is discussed. The potential
      ability of C. iridescens as a biomonitor of metallic pollutants is postulated.

PMID- 11584635
TI  - The ability of apoplastic ascorbate to protect poplar leaves against ambient
      ozone concentrations: a quantitative approach.
AB  - Shoots of a sensitive (Populus nigra 'Brandaris') and a more tolerant (Populus
      euramericana 'Robusta') poplar clones were exposed for 30 days to Filtered Air or
      ambient O3-concentrations in fumigation cabinets. At regular intervals were
      determined: gas exchange of the leaves, the internal air space (Vair) and
      apoplastic water volume (Vapo) and the reduced (ASA) and oxidized (DHA) ascorbate
      concentration in the apoplast and in the mesophyll cells. The apoplastic ASA
      concentration was 0.2 mM at the start of the experiment for both cultivars, while
      the effective cell wall thickness, estimated from Vapo, varied from 0.3 to 0.6
      micron. Model calculations revealed that only 30% of the O3 molecules entering
      the apoplast was intercepted at these values. The O3-treatment induced a decline
      in stomatal conductance, an increase in Vapo and in the apoplastic ASA
      concentration. As a result the estimated O3-flux to the cell membrane strongly
      declined. However, these responses occurred after the O3-induced reduction in
      photosynthesis. Moreover, they did not prevent early senescence of the leaves at
      a prolonged exposure. Therefore, it is concluded that the increase in apoplastic
      ASA-concentration was rather a general stress reaction of the affected poplar
      leaf than a (specific) defence reaction induced by O3. Our results suggest that
      other factors than the scavenging efficiency of apoplastic ASA were responsible
      for the difference in O3 sensitivity between both poplar cultivars.

PMID- 11584636
TI  - Airborne uranium contamination--as revealed through elemental and isotopic
      analysis of tree bark.
AB  - A new strategy for characterisation of airborne uranium contamination based on
      ICP mass spectrometric analysis of tree bark is described. The uranium content of
      tree barks (50 samples) obtained from diverse locations (remote, rural,
      industrial) varied over almost four orders of magnitude (0.001-8.3 micrograms/g
      U) with maximum concentrations recorded in the vicinity of a nuclear fuel
      fabrication plant (0.70-8.3 micrograms/g U). Elevated concentrations were also
      observed near a coal-fired power station (0.25-0.38 microgram/g U). Isotopic
      analysis revealed significant deviation from the natural uranium isotope ratio
      (235U/238U, 0.00725) at four nuclear installations (235U/238U, 0.0055-0.0097).
      These findings indicate that tree bark serves as an effective biomonitor for
      uranium and, with isotopic analysis, discrimination between nuclear and non
      nuclear emissions is realised.

PMID- 11584637
TI  - Accumulation status of persistent organochlorines in albatrosses from the North
      Pacific and the Southern Ocean.
AB  - Current status of contamination by persistent organochlorines (OCs) such as
      polychlorinated biphenyles (PCBs), dichlorodiphenyl trichloroethane and its
      metabolites (DDTs), isomers of hexachlorocyclohexane (HCHs), hexachlorobenzene
      (HCB) and chlordane compounds (CHLs) were examined in 61 individuals belonging to
      eight albatross species collected from the North Pacific and the Southern Ocean.
      Generally high OC concentrations were found in albatrosses from the North Pacific
      than those from the Southern Oceans. Black-footed albatrosses had noticeably high
      PCBs and DDTs concentrations with mean values of 92 and 33 micrograms/g wet
      weight in subcutaneous fat, respectively. Among the other OCs, concentration of
      CHLs was higher than that of HCB in North Pacific albatrosses. HCHs accumulation
      was the lowest among all the OCs analyzed. Species-specific differences were
      observed for HCB, CHLs and DDTs in some species in the Southern Ocean. No
      significant difference of gender and age-related accumulation was observed in
      total OCs. However, PCB concentrations were higher in mature birds than those
      from immature ones in the Southern Ocean. Species-specific accumulation patterns
      of OCs in albatrosses were closely related with their feeding, migration, age and
      geographical ranges.

PMID- 11584638
TI  - Full life-cycle toxicity assessment using rotifer resting egg production:
      implications for ecological risk assessment.
AB  - The majority of standardized toxicity tests incorporate only a fraction of the
      test organism's life-cycle. However, in natural ecosystems, organisms may be
      exposed at various times during their life-cycle or throughout their life-cycle.
      Thus, ecotoxicological data from standardized toxicity tests is of limited
      ecological relevance. Existing standardized toxicity tests using the freshwater
      rotifer Brachionus calyciflorus utilize 24-h survival or 48-h asexual
      reproduction as endpoints, despite evidence that sexual reproduction is more
      sensitive. A 96-h B. calyciflorus resting egg toxicity test was developed and
      used to estimate the toxicity of pentachlorophenol (PCP) and copper. Results were
      compared to a variety of acute and sublethal endpoints for both toxicants. The B.
      calyciflorus 96-h resting egg production NOEC for PCP of 10 micrograms/l was 20
      times lower than the 48-h asexual reproduction no observed effect concentration
      (NOEC) and 120 times lower than the 24-h acute lethal concentration 50%. The 96-h
      resting egg production NOEC for copper of 2.8 micrograms/l was 7 times lower than
      the 48-h asexual reproduction NOEC and nine times lower than the 24-h acute LC50.
      Resting egg production was a more sensitive indicator of toxicity than several
      other sublethal endpoints as well. These results indicate that partial life-cycle
      toxicity tests are not sufficiently sensitive to detect ecologically relevant
      adverse effects.

PMID- 11584639
TI  - Changes in the leachability of metals from dredged canal sediments during drying
      and oxidation.
AB  - The behaviour of metals in canal sediments after their disposal to land has
      important implications for the environmental management of canal dredgings. The
      leaching behaviour of trace metals was investigated in a laboratory-based
      experiment using sediment from a canal in the UK (139 mg Zn kg-1dry sediment, 1.1
      mg Cd, kg-1dry sediment 31.5 mg Cr kg-1dry sediment, 20.6 mg Cu kg-1dry sediment
      48.4 mg Ni kg-1dry sediment, 43.4 mg Pb kg-1dry sediment and 7.6 mg As kg-1dry
      sediment). The sediment was allowed to dry. Cores (10 cm long) of the drying
      canal sediment were taken over a period of 12 weeks. A simple water extraction
      procedure was used to investigate changes in metal leachability at varying depths
      through the cores. Metal leachability increased over the first five weeks of
      drying and then subsequently decreased between weeks five and twelve, (e.g. Cd
      increased from approximately 0.006 to 0.018 mg/kgsediment then decreased to
      approximately 0.006 mg/kgsediment, Zn increased from approximately 1.5 to 3
      mg/kgsediment and then decreased to approximately 1.5 mg/kgsediment). These
      results were combined with sulphide/sulphate ratios, which showed a decrease as
      the sediment dried (e.g. at 2-4 cm depth from approximately 1 to 0.49), and BCR
      sequential extraction data. Most metals (except Cd and As) showed a
      redistribution from the residual phase into more mobile phases as the sediment
      dried and oxidised. Metal leachability was strongly correlated with the
      sulphide/sulphate ratio with leachability normally increasing with decreasing
      sulphide/sulphate ratio. The combined results were used to infer the likely
      behaviour of dredged material upon disposal to land.

PMID- 11584641
TI  - A comparison of indigenous mosses and topsoils for use in monitoring atmospheric
      heavy metal deposition in Galicia (northwest Spain).
AB  - Samples of moss (Scleropodium purum or, in its absence, Hypnum cupressiforme) and
      of topsoil (0-5 cm) were collected in the spring of 1995, from 75 sites
      distributed throughout Galicia (northwest Spain) in order to compare the
      potential usefulness of each in evaluating the atmospheric deposition of
      contaminants. Analysis was made of the total content of various metals in the
      moss and of different soil metal fractions (including total metal content, labile
      metals and metals bound to organic material). We found that the labile fraction
      most closely resembled the metal content of the moss. Calculation of enrichment
      factors allowed us to show that the soil was not, except in the case of Cr, the
      main source of contamination in the moss. By comparing contamination factors of
      metals in moss and soil fraction samples we found that moss samples were more
      useful for evaluating the degree of contamination at different sites.

PMID- 11584640
TI  - Levels of short and medium chain length polychlorinated n-alkanes in
      environmental samples from selected industrial areas in England and Wales.
AB  - Electron capture or negative ion chemical ionisation gas chromatography-mass
      spectrometry was employed to measure concentrations of short and medium chain
      length polychlorinated n-alkanes extracted from samples of water, river sediment,
      benthos, fish, soil, digested sewage and earthworms. Analysis of samples from 20
      aquatic and eight agricultural sites indicated that short and medium chain length
      polychlorinated alkanes were present in the following concentration ranges:
      sediment < 0.2-65.1 mg/kg dry weight, water < 0.1-1.7 micrograms/l, fish < 0.1
      5.2 mg/kg wet weight, benthos < 0.05-0.8 mg/kg wet weight, digested sewage 1.8
      93.1 mg/kg dry weight, soil < 0.1 mg/kg dry weight, and earthworms < 0.1-1.7
      mg/kg wet weight. It is clear from this study that these compounds are widely
      distributed in the UK environment, although it is not yet possible to fully
      assess the risks posed to either wildlife or humans by their continued use.
      Further study of these compounds is indicated.

PMID- 11584642
TI  - Response of mosses to the heavy metal deposition in Poland--an overview.
AB  - Concentrations of heavy metals (Cd, Cr, Cu, Fe, Ni, Pb, Zn) in Pleurozium
      schreberi (Brid.) Mitt., a common moss species, were used to indicate relative
      levels of atmospheric deposition in Poland in the years 1975-1998. Spatial and
      temporal differences in the heavy metal concentrations in mosses were found. The
      highest concentration of heavy metals was recorded in the moss samples from the
      southern, most industrialised part of the country, and the lowest from north
      eastern Poland. A significant decrease of heavy metals over 20 years (1975-1998)
      was found.

PMID- 11584643
TI  - Sodic soils reclaimed with by-product from flue gas desulfurization: corn
      production and soil quality.
AB  - Interest is growing in the use of by-product from flue gas desulfurization (FGD)
      to reclaim sodic soils by controlling the pH and excessive Na+. This study
      evaluated the effects on corn (Zea mays) production and pH and electrical
      conductivity (EC) of calcareous sodic soil during four times of cultivation when
      the by-product was applied once at the first cultivation (Study I) and the
      impacts on plant and soil quality at first cultivation when the by-product was
      applied to the soil at 23,000 kg ha-1 (Study II). In Study I, the germination
      rate and corn production increased by applying the by-product (0, 5,800, 11,600,
      and 23,100 kg ha-1), and the greatest total amounts of corn production during the
      four times of cultivation was when the by-product was applied at 23,100 kg ha-1.
      In Study II, the pH, exchangeable sodium percentage (ESP), clay dispersion and
      soluble Na+ in the soil decreased and soluble Mg2+ and soluble K+ in the soil
      increased. The soil pH was reduced from 9.0 to 7.7 by applying the by-product.
      However, the by-product decreased the concentrations of total N and P in corn
      leaves in this study. No significant difference in the concentrations of Mo, Zn,
      Pb, Ni, Cd, Mn, Cr, Cu, and Al in corn leaves and the soil was observed between
      the by-product addition and the control except for B in the soil and Fe in corn
      leaves. The concentration of B in the soil was reduced from 28.7 mg kg-1 to 25.4
      mg kg-1 and the concentration of Fe in corn leaves increased from 17.5 mg kg-1 to
      22.6 mg kg-1 by applying the by-product in our study.

PMID- 11584644
TI  - Airborne heavy metal pollution and its effects on foliar elemental composition of
      Empetrum hermaphroditum and Vaccinium myrtillus in Sor-Varanger, northern Norway.
AB  - Uptake of Al, Cu, Fe, Mn, Ni, Ca, K, Mg, P, and S in Empetrum nigrum L. ssp.
      hermaphroditum Hagerup and Vaccinium myrtillus L. from Ni, Cu and SO2
      contaminated sites in Sor-Varanger, northern Norway, were investigated. The
      primary objective was to study the effect of airborne heavy metal pollution on
      foliar element composition of these two dwarf shrubs. Ni distribution and
      availability in soils clearly indicate atmospheric deposition of Ni particulates
      in Sor-Varanger. Foliar Ni concentrations in E. hermaphroditum and V. myrtillus
      increased in relation to plant available Ni in corresponding soils. Leaves of E.
      hermaphroditum generally contained higher concentrations of Ni than leaves of V.
      myrtillus. Emissions influenced some features of leaf elemental composition of
      the two species in very different ways. In leaves of V. myrtillus, S increased in
      proportion to Ni and Cu, while levels of Mn decreased. In leaves of E.
      hermaphroditum, Fe increased in proportion to Ni and Cu, while levels of Ca
      decreased.

PMID- 11584645
TI  - Biological monitoring: lichens as bioindicators of air pollution assessment--a
      review.
AB  - Often as part of environmental impact studies and, above all, to obtain
      authorisations in accordance with prescriptions from the Ministry for the
      Environment (Italy), surveys and controls that use biological indicators are
      required. This is because such indicators are valid instruments for evaluating
      the quality of the air ensuing from the subject (often an industrial plant) of
      the Environmental Impact Assessment (EIA). In this context, this paper aims to
      analyse some of the theoretical aspects of biological monitoring and to provide a
      progress report on the use of lichens as bioindicators of air quality, with a
      particular eye to the situation in Italy. The object of this paper is that of
      pointing out the most important lines in the current state of knowledge in this
      field, evaluating the methodological applications and their
      advantages/disadvantages with respect to traditional surveying methods.

PMID- 11584646
TI  - Fewer bells and whistles, but IVR (interactive voice response) gets the job done.

PMID- 11584647
TI  - DM at the crossroads: survey highlights continuing challenges facing a young
      industry.
AB  - While the number of chronic diseases addressed by DM efforts is on the rise, only
      a small percentage of individuals who could be helped by such efforts are
      enrolled in formal DM programs. Further, the group which is most impacted by
      chronic disease--Medicare beneficiaries--is least likely of all to have access to
      DM activities. Check out these and other findings from a status report on the DM
      industry--where it has been, and where it is going.

PMID- 11584648
TI  - Group approach to prenatal care garners enthusiasm among patients and providers.
AB  - Without a marketing plan or fanfare, a group-care model aimed at delivering
      prenatal care to women with common concerns has gained an established foothold in
      at least 20 health care settings. Further, the Centering Pregnancy model is now
      getting new attention from researchers because of the potential benefits it may
      offer to teen groups and other ethnic populations. See how this self-empowering
      plan of care works, and why many satisfied patients and providers prefer it over
      more traditional prenatal care delivery.

PMID- 11584649
TI  - Report highlights gaps in care for older asthmatics.
AB  - Because new research suggests that there is a disparity between the care
      delivered to this population versus younger asthma patients. And perhaps as a
      result, asthmatics over the age of 70 are hospitalized for asthma-related reasons
      at more than twice the rate of younger adults. Researchers at Johns Hopkins
      University have uncovered shortcomings in the education, self-care skills, and
      pharmacologic management of these older patients. Get the details on this
      research and find out what you can do to shore up care and reduce utilization for
      this population.

PMID- 11584650
TI  - [Malaria research at the IMTSSA le Pharo].

PMID- 11584651
TI  - [Methods to study drug resistance of Plasmodium falciparum to quinolines].

PMID- 11584652
TI  - [African Quin: results of a pragmatic study on the diagnosis of uncomplicated
      malaria attacks and treatment using quinine in French-speaking Africa].
AB  - Management and treatment of disease do not always conform with official
      recommendations. African-quin is a pragmatic multicentric study carried out in 13
      African countries to evaluate non-conformities in the management and treatment of
      uncomplicated malarial attacks using quinine. This study involved a total of
      3,981 patients with documented uncomplicated malarial attacks diagnosed by 500
      clinical physicians. Physicians were supplied with quinine tablets (125 mg et 500
      mg Quinimax containing 125 mg and 500 mg of quinine base respectively) to allow
      treatment according to the dose recommendations of the WHO (24 mg/kg/day of
      quinine base). In 38% of the 3,981 patients, diagnosis was based on clinical
      findings without measurement of parasitemia. The median dose of Quinimax was 15.4
      mg/kg/day in 3 intakes in 67% and 2 intakes in 33%. The dose was 23.2 mg/kg/day
      for patients under 12 years and 14.7 mg/kg/day for patients over 18 years (p <
      0.001). Treatment lasted for at least 5 days in 62% of patients. Fever control
      was achieved within a mean delay of 3.9 +/- 1.5 days and was followed by a rapid
      decrease in clinical symptoms. Clinical control (normal temperature) was obtained
      in 96% of patients. The dose of Quinimax was the same regardless of whether
      treatment was a success or failure. The results of this study demonstrate the gap
      between official recommendations and everyday clinical practice and raise several
      important questions concerning the basis for decision-making, treatment goals,
      drug dosage, and treatment duration.

PMID- 11584653
TI  - [Diagnosis of malaria attacks in endemic areas: theoretical aspects and practical
      implications].
AB  - What criteria can be used to diagnose malaria in health centers located in
      endemic areas? Can an algorithm be developed for management of fever episodes?
      What parameters should be used to assess the morbidity of malaria for public
      health surveys or for studies to determine the efficacy insecticide-impregnated
      bednets, drug prophylaxis protocols, or anti-malarial vaccinations? Finding a
      useful definition for malaria attack is a perennial problem that becomes more
      difficult to resolve as the transmission rate and immunity level of the
      population increases. This review presents the fundamental aspects of diagnosing
      malaria. The choice of diagnostic technique requires knowledge of
      physiopathological, epidemiological, and clinical features. There is no single
      method. It depends on the circumstances, epidemiological context, available
      facilities, and goals. Diagnosis for treatment is one thing. Diagnosis for
      evaluation is another. In addition to discussing these concepts, this article
      provides references from the recent literature and up-to-date information needed
      to deal with the problem of diagnosing malaria attacks in endemic areas.

PMID- 11584654
TI  - Development of new drugs for chemoprophylaxis of malaria.
AB  - When U.S. troops first encountered drug resistant malaria during the Vietnam war,
      the United States Army responded by establishing a malaria drug research program.
      In 1988, the Walter Reed Army Institute of Research developed mefloquine (WR
      149240) and halofantrine (WR 171669). Actually, in association with SmithKline
      Beecham, the WRAIR is developing tafenoquine (WR 238605), an analog of
      primaquine, which is expected to be effective in both preventing and treating
      malaria in deployed military personnel. Final phase III studies leading to U.S.
      Food and Drug Administration approval are planned for 2000. Applied research is
      also carried out with the association atovaquone-proguanil (Malarone) or with
      azithromycin, but also with primaquine, the associations paludrine-dapsone or
      lapudrine-dapsone, analogs of floxacrine (WR 243251), and a guanylhydrazone (WR
      182393). The future scientific directions must focus on basic and applied
      research for a better understanding of the modes of action and mechanisms of
      resistance to standard and developmental drugs. Using new techniques, the design
      and synthesis of new drugs would hopefully result in the development of drugs
      that circumvent the malaria parasites elusive mechanisms of drug resistance.

PMID- 11584655
TI  - [Antimalarial prophylaxis for the traveler or in the armed forces].

PMID- 11584656
TI  - [Antimalarial chemoprophylaxis in the French army: development from 1986 to
      2001].
AB  - In 1999, almost 25,000 French soldiers were deployed in malaria transmission
      areas. With an incidence of 4.5 p. 100 men.year, malaria infection remains a
      serious problem requiring priority status for control in military personnel.
      Epidemiological surveillance provides data necessary to assess morbidity due to
      malaria, monitor changing patterns of Plasmodium falciparum drug-sensitivity, and
      evaluate the efficacy of malaria control measures. In 1990, the French army
      replaced chemoprophylaxis using chloroquine alone with combination treatment
      using a single capsule containing 100 mg of chloroquine base and 200 mg of
      proguanil chlorhydrate. This measure in association with the use deltamethrine
      impregnated bed-nets led to a significant decrease in incidence. However a
      comeback was observed from 1993 to 1997. Since 1995, the effectiveness of the
      chloroquine-proguanil combination has diminished mainly in the stable malaria
      areas. In response to increasing Plasmodium falciparum resistance to chloroquine
      proguanil chemoprophylaxis, it was necessary to find an alternative. Two studies
      carried out among French soldiers in Sub-Saharian Africa between 1996 and 1998
      demonstrated that a daily dose 100 mg doxycycline was more effective than the
      chloroquine-proguanil combination. In addition the 1998 study showed that
      doxycycline monohydrate in the form of a multiparticle tablet was better
      tolerated. In 2001 four drugs are used for malaria chemoprophylaxis in the army
      personnel, i.e., chloroquine and proguanil in combination, mefloquine, and
      doxycycline, depending on location and duration of mission. The chloroquine
      proguanil combination is used in countries with chloroquine-resistant strains,
      e.g., Chad and Senegal. Mefloquine and doxycycline are used in countries with
      chloroquine-resistant strains. Due to increasing resistance, it will be necessary
      to evaluate other drugs or antipaludian combinations.

PMID- 11584657
TI  - Malaria prophylaxis/radical cure: recent experiences of the Australian Defence
      Force.
AB  - Since the eighties, the Australian Defence Force has deployed soldiers in malaria
      endemic areas: Cambodia, Somalia, Rwanda, Bougainville, and East Timor.
      Currently, doxycycline is used as first line prophylactic drug and mefloquine is
      recommended for those who cannot tolerate the antibiotic. In 1998, the Australian
      Defence Force participated in the evaluation of tafenoquine for prophylaxis of
      both falciparum and vivax malaria in Thai soldiers. At the completion of this six
      month study, 29 of 205 soldiers had come down with malaria including eight with
      falciparum malaria, 20 with vivax malaria, and one with mixed infection. A total
      of 28 of the 101 soldiers in the placebo group were infected with malaria as
      compared with only one of the 104 soldiers in the tafenoquine group. In 1999,
      another study was started on the island of Bougainville to compare the
      effectiveness a 3-day course of tafenoquine and a 14-day course of primaquine for
      radical cure of vivax malaria. At the present time, 411 soldiers have completed
      the study including 201 in tafenoquine arm and 210 in primaquine arm. Seven
      soldiers in each arm developed vivax malaria after returning to Australia. These
      results indicate that tafenoquine is not superior to primaquine in preventing
      vivax malaria. However study participants preferred the shorter course using
      tafenoquine and operationally it was found to be more suitable than primaquine.

PMID- 11584658
TI  - The Italian army standpoint on malaria chemoprophylaxis.
AB  - Soldiers on duty in tropical areas are at high risk of malaria and need
      chemoprophylactic regimens which may ensure the best efficacy, tolerability and
      compliance. Current Italian Army guidelines are based on recent military
      experiences in tropical areas, where mefloquine prophylaxis was as well tolerated
      as combination treatment with chloroquine and proguanil but more effective and
      easier to comply with, at least among soldiers. Chloroquine alone (300 mg base
      once/week) is prescribed for areas without chloroquine-resistant Plasmodium
      falciparum, while mefloquine (250 mg once/week) is recommended for areas with
      chloroquine-resistance. Doxycycline is the first choice regimen for mefloquine
      resistant areas and an alternative to mefloquine when this medication is
      contraindicated or not tolerated. The combination chloroquine-proguanil
      represents the alternative chemoprophylactic regimen when mefloquine and
      doxycycline are contraindicated or not tolerated.

PMID- 11584659
TI  - The malaria threat.
AB  - The British experience of the past two decades indicates that fixed-schedule
      chemoprophylaxis is difficult because of the variety of epidemiological
      situations and increasing incidence of drug resistance. Of the 110 cases of
      malaria contracted in Kenya between 1982 and 1996, 74% were due to Plasmodium
      falciparum. Of the 45 malaria infections contracted in Belize, 84% were due to
      Plasmodium vivax. In 1985 the fixed drug combination of chloroquine base 300 mg
      weekly plus proguanil 200 mg daily was adopted as standard chemoprophylaxis for
      use in all parts of the world where chemoresistant Plasmodium falciparum had been
      observed. Mefloquine was recommended as first-line prophylaxis in Papua New
      Guinea in 1986 and in East Africa in 1993. Doxycycline hyclate was prescribed in
      September 1999 when a Gurkha company was deployed on peacekeeping duties to East
      Timor, but its effectiveness has not yet been evaluated. Chemoprophylaxis must be
      combined with non-drug antimalaria technologies, especially insecticide-treated
      bed nets.

PMID- 11584660
TI  - Malaria prevention and control in the United States military.
AB  - Malaria continues to be a serious threat to deployed military forces in many
      areas of the World. United States experiences during, and lessons learned from,
      World War II, Viet Nam, and Somalia have significantly changed the way that
      military planners, medical and preventive medicine personnel are facing the
      malaria challenge. Currently, the US military has a powerful arsenal of
      educational courses and materials, personal protective measures, and malaria
      surveillance and control techniques in place to fight malaria. These new tools
      will hopefully reduce malaria morbidity and mortality during military deployments
      in the future.

PMID- 11584661
TI  - Experiences with malaria chemoprophylaxis in Dutch troops.
AB  - This article describes the situation for malaria chemoprophylaxis among Dutch
      military personnel. Any malaria chemoprophylaxis advice given to Dutch troops is
      based on a close co-operation between national military and civilian experts.
      Most studies, related to a deployment in Cambodia, describe the experiences with
      mefloquine. Overall it has been well tolerated. From an African deployment, it
      has been learned that anticircumsporozoite antibodies could be demonstrated in
      11% of the personnel. Future options for Dutch troops will concentrate on
      atovaquone/proguanil and tafenoquine. Furthermore some kind of individualisation
      will be accepted. In conclusion malaria in Dutch troops has remained a manageable
      problem but vigilance remains necessary.

PMID- 11584662
TI  - Malaria prophylaxis in the French armed forces: evolution of concepts.
AB  - Malaria is still a serious public health problem in the world and control remains
      a major priority for the approximately 25.000 French troops deployed, mostly on
      permanent assignment, in malaria transmission regions. Epidemiological
      surveillance of malaria provides data necessary to assess morbidity, monitor
      changing patterns of Plasmodium falciparum drug-sensitivity, and evaluate the
      efficacy of malaria control measures. About 540 cases were observed in 1999 for
      an incidence of 4.1 p. 100 men. year. Since 1991, strong emphasis has been placed
      on prophylaxis. In addition to vector control measures and individual protection
      against mosquito bites (impregnated bednets, protective clothing, application of
      repellents, and indoor insecticide spraying), drug prophylaxis has been
      recommended using a combination of 100 mg of chloroquine and 200 mg of proguanil
      chlorhydrate (CQ + PG) in a single capsule manufactured by the French Health Army
      Service. Initially this policy led to a significant decrease in malaria cases
      among French soldiers. However the incidence of malaria rose in 1995 and 1996.
      This recrudescence was attributed to poor compliance with chemoprophylaxis and to
      the declining efficacy of the CQ + PG combination. In response to these problems,
      a new policy was implemented especially in countries where cycloguanil-resistant
      Plasmodium falciparum incidence rate is increasing. The new chemoprophylactic
      regimen calls for a personal prescription of mefloquine. Doxycycline monohydrate
      is used in case of mefloquine contra-indication or intolerance. Combination of CQ
      + PG delivered in a single capsule remains a suitable chemoprophylactic regimen
      in Sahel countries as well as Horn of Africa.

PMID- 11584663
TI  - [Malaria prevention in the army: experience in senegal].
AB  - The Senegalese army has acquired extensive experience in malaria prophylaxis in
      Sub-Saharan Africa. Until the early 90s, chloroquine-based drug prophylaxis was
      routinely administered during the transmission season. Currently this policy has
      been abandoned inside the country in favor of early treatment of infection. This
      change was made possible by the presence of qualified staff in all barracks. For
      extraterritorial interventions in Sub-Saharan Africa, drug prophylaxis is still
      used since most of the Senegalese population lives in the Sahelian zone without
      immunity to malaria and most host countries are in areas of high transmission.
      Treatment protocols have been defined in function of Plasmodium drug sensitivity
      in each country. For all West African nations except Nigeria, the protocol
      involves a combination of choroquine and proguanil at a dose of 300 mg per week
      and 200 mg per day respectively. For Central African nations in the south and
      east as well as for Nigeria, either mefloquine at a dose of 250 mg per week or
      doxycycline at a dose of 100 mg per day are used. Although acceptance has been
      slow, use of impregnated bednets is now an integral part of the prevention
      strategy. The insecticide used inside the country is deltametrin, but other
      products may be used during extraterritorial operations depending on vector
      sensitivity in the facilities host country. Vector control by spraying of
      insectides in and eliminating larval deposits is also an important part of the
      prevention strategy used by the Senegalese army which maintains a mobile unit for
      that purpose.

PMID- 11584665
TI  - [In the pursuit of malaria].

PMID- 11584664
TI  - [Disease vector control strategy in the French army].
AB  - Disease vector control is a major priority for the Medical Health Corps of the
      French Armed Forces which maintains around 23,000 troops in tropical areas and is
      involved in numerous military and humanitarian missions throughout the world.
      Control strategy includes both general and personal control measures. Personal
      control measures include wearing permetherin-impregnated combat uniforms,
      application of repellents to the skin, and use of deltamethrin-impregnated
      bednets. General measures are implemented in facilities and in the environment.
      Measures in facilities include not only physical deterrents such as screens on
      openings and air-conditioning but also application of chemical insecticides to
      walls, curtains, and screening. Environmental measures include control of larval
      deposits and elimination of potential breeding areas. Low-volume wide-area
      spraying of imagocides is a supplemental option used in case of disease outbreak.
      For units stationed in tropical areas, command and surveillance of vector control
      operations is under the responsibility of the mosquito control committee which
      includes personnel from the affected field unit. Strategies are chosen in
      function of local climate and operational conditions. The efficacy of vector
      control programs is assessed annually by reviewing the incidence in armed forces
      personnel of the main vector-transmitted diseases: malaria, dengue fever, and
      leishmaniasis. Documentation and training are dispensed to all units stationed in
      tropical areas. To ensure that knowledge of military physicians remains current,
      three courses on malaria control are offered each year at the Tropical Medicine
      Institute of the Armed Forces Health Corps (Le Pharo) in Marseille. Field
      research conducted in collaboration with military or civilian organizations
      independent of the Armed Services Health Corps makes it possible to keep chiefs
      of staff informed of state-of-the art vector control measures adapted to use by
      personnel on assignment or mission in tropical areas.

PMID- 11584666
TI  - An evidence-based vector control strategy for military deployments: the British
      Army experience.
AB  - We describe the British Army's current strategy for controlling arthropod vectors
      of disease during overseas deployments. Military commanders and medical officers
      have different, but complementary responsibilities in achieving vector control.
      In this paper we define a hierarchy of evidence-based vector control guidelines.
      Field guidelines must be based on the best available research evidence,
      preferably that derived from pragmatic randomised controlled trials (RCTs), and
      from systematic reviews of trials. Assessing the effectiveness of different
      vector control measures involves a trade-off between the relative benefits and
      harm of different technology options. There is compelling scientific evidence
      that bed nets and screens treated with a pyrethroid insecticide are highly
      effective in protecting against nocturnally active, anthropophilic arthropods
      (including ectoparasites), and will reduce the incidence of malaria,
      leishmaniasis, lymphatic filariasis and Chagas' disease. Etofenprox and
      deltamethrin are the safest pyrethroids, and permethrin the least safe. Vector
      control strategies of probable effectiveness are the use of insecticide-treated
      clothing, the wearing of protective clothing, and the correct use of DEET-based
      topical insect repellents. Aerosol insecticides are of debatable effectiveness.
      Other effective vector control measures, of limited usefulness during
      deployments, include electric fans, mosquito coils/vaporising mats, and smoke.
      "Biological" vector control measures, and insect buzzers/electrocuters are
      ineffective. Practical insect avoidance measures, based on an understanding of
      vector biology, complete the military vector-control arsenal. We conclude that
      practical insect avoidance measures, combined with pyrethroid-treated nets and
      clothing, and DEET-based topical repellents, can achieve almost 100% protection
      against biting arthropods.

PMID- 11584667
TI  - [The prescription of repellents].
AB  - Repellents are chemical products designed to ward off insects. They are effective
      against a wide range of arthropods including mosquitoes and flies but not against
      bees and wasps. Choosing the proper repellent can be difficult because no single
      product repels all pests. This article compares the performance and toxicity of
      various repellents based on reports describing systemic, topical, or physical
      repellents made from natural or synthetic ingredients. Essential oils are the
      most common natural ingredient. Synthetic ingredients range from dimethyphtalate,
      ethylexanediol, and diethyltoluamide (DEET) to new molecules such as 35/35,
      piperidine, bayerepel, and KBR 3023. Our findings indicate that DEET, used as the
      gold standard in most studies, is still the most effective repellent. There is no
      synergy between any of these products but combinations (e.g. ethylhexanediol and
      DEET) can optimize protection. In conclusion we propose guidelines for
      prescribing repellents to achieve the required level of protection in function of
      the duration of exposure and benefit-to-risk ratio. Several recommendations are
      made on the safe use repellents for adults and children.

PMID- 11584668
TI  - [Diagnosis and treatment of a case of obstructive sleep apnea syndrome with
      AutoSet].
AB  - The author presents the case of a male patient with obstructive sleep apnoea
      syndrome, in which the use of classic CPAP therapy after performing an uvulo
      pharyngoplasty (UVPP) led to very good results. The pressure levels determined
      initially after a polysomnography with Apnoe Check were compared with the results
      of the measurements with another device, AutoSet, used for the first time in our
      country. This allowed the tapering of pressure levels for CPAP and also revealed
      other advantages of the device, reviewed here.

PMID- 11584669
TI  - [Paraneoplastic thrombosis of subclavian and right internal jugular veins.
      Clinical case].
AB  - A clinical case of the "Paraneoplasic thrombosis of subclavian vein and right
      internal jugular vein", is presented at a young patient, with right lung
      carcinomatous lymphangitis, clinically confirmed by BAL with probable prostatic
      point of start.

PMID- 11584670
TI  - [The indications of bronchial resection and anastomosis in lung cancer].
AB  - Bronchial resection and anastomosis represents an alternative to the
      pneumonectomy in patients with severe impairment of pulmonary function and/or
      other diseases which make such radical surgery too risky. The authors present two
      clinical cases of right upper lobe lung cancer (a squamous-cell carcinoma and an
      adenocarcinoma) admitted in the Thoracic Surgery Department of the National
      Institute of Pulmonology "Marius Nasta" from Jan-March 2001, in which they could
      not perform pneumonectomy because of unacceptable high risks. In both patients a
      right upper lobectomy with "sleeve" resection was done, with the anastomosis of
      right main bronchus to the intermediary one. The clinical, bronchoscopic and
      functional results were excellent. The literature review also shows very good
      results of this technique in the surgical treatment of lung cancer. For these
      reasons, the authors recommend this procedure in all the cases in which it can be
      technically applied; more than that, the survival rate is similar with other more
      radical techniques, but without any complications.

PMID- 11584671
TI  - [Controversies in the treatment of non-small cell lung cancer; adjuvant
      chemotherapy].

PMID- 11584672
TI  - [Possibilities of improvement of chemotherapy in bronchial cancer].

PMID- 11584673
TI  - [Which is your diagnosis ? ].

PMID- 11584674
TI  - [The habit of smoking cigars - less dangerous than smoking cigarettes ?]].

PMID- 11584675
TI  - [Tuberculosis incidence in Romania in first trimester of 2001].

PMID- 11584676
TI  - [Evolution of tuberculosis in the District of Dolj].
AB  - The 742,500 inhabitants of Dolj District face a high risk of TB since over 10
      years. In 1992 the TB incidence was 93.7@100,000 and 155.7@100,000 in 2000 (66%
      increase). A number of 1156 TB patients were registered in year 2000, 84% new
      cases and 16% relapses. 82% of the patients had lung lesions, 11.9% had pleurisy
      and 6.1% had various extra-thoracic lesions. Bacteriologic confirmation was
      67.7%. The periodic prevalence of smear positive patients, with a high level of
      139@100,000 in 1999, determined a high risk for disease among children, also, the
      TB incidence in this category being 46.8@100,000. The evaluation of treatment
      results in a cohort of smear positive patients registered in 1999 showed a
      success rate of only 75.5%. The decrease of the TB endemy level in Dolj district
      depends on improvement of life status in the district, complete use of DOTS and a
      good financement of all parts of the National TB Control Program in 2001-2005.

PMID- 11584677
TI  - [Test for determination of attention in patients with sleep apnea syndrome].
AB  - To investigate the daytime sleepiness in patients with sleep apnea syndrome, we
      used a test for measurement of sustained attention. The present study was
      performed on 65 participants: 10 healthy non-snoring volunteers, 25 snoring
      volunteers and 30 patients with symptoms of sleep apnea. The error rate
      (percentage of incorrect responses) appears to be most suitable for the
      evaluation of the test. The difference between the habitual snorers and the
      healthy non-snoring volunteers was statistically significant. At the apneic
      patients, there are significant differences in age, sex, and body mass index;
      attention decreases significantly in the last 10 minutes of the test. The
      attention test can be helpful for the measurement of daytime sleepiness in apneic
      patients.

PMID- 11584678
TI  - [Tuberculosis - HIV/AIDS associated cases registered in Department of Mures
      between 1994- 1999 ].
AB  - Tuberculosis--HIV/AIDS associated cases registered in the Department of Mures
      between 1994-1999 are under a low rate--24 patients, meaning 0.69% of all
      tuberculosis cases. 79% of these were children (7.1% of the tuberculosis in
      children). There was a dominance of the pulmonary location (22-91.5%). The
      bacteriologic confirmation among these cases is low: 37.5% vs. 66.5% in HIV
      negative patients; this imposes the improvement of the diagnosis using methods as
      bronchoscopy, hemocultures, biopsies and modern bacteriological methods as Bactec
      and molecular biology in these cases. In 62.5% of the cases the tuberculosis
      diagnosis was established by combining epidemiological, clinical, radiological
      and biological data. Skin test was positive in 12.5% of the cases. The clinical
      and radiological data showed aspects near to the common pulmonary tuberculosis,
      but with a high rate of the complicated forms in children (66.6%). 14 patients
      (58%) originated from a positive-contact environment. The standard treatment was
      well tolerated in 91.6% of the cases; there were 2 side effects to PZM and EMB.
      The evolution under treatment was generally favorable; there were 2 deaths with
      AIDS during active tuberculosis. The early diagnosis of HIV infection in high
      risk patients and of the latent tuberculous infections would allow the decrease
      of the rate of this high-gravity associated illness.

PMID- 11584679
TI  - [Monocrotaline induce pulmonary hypertension in animal models].
AB  - The pulmonary hypertension is a serious disease, difficult to treat, and its
      mechanisms remain however to be elucidated. It is known that administration of
      small doses of MCT or its active metabolite, monocrotaline pyrrole (MCTP); to
      rats causes delayed and progressive lung injury characterized by pulmonary
      vascular remodeling which induces pulmonary hypertension. The purpose of this
      article is to get used to vascular, cellular and molecular changes in pulmonary
      hypertension, in order to create a personal experimental animal model. This
      experimental model will try to find new ways of therapeutical strategies in human
      pulmonary hypertension.

PMID- 11584680
TI  - [Hypersensitivity pneumonitis].
AB  - Hypersensitivity pneumonitis (HP) is an interstitial lung disease associated with
      repeated exposure to a wide range of inhaled organic dusts and related
      occupational allergens. Immunological phenomena have been reported to play an
      essential role in initiating and maintaining the disease. Natural history,
      clinical findings, chest radiography, pulmonary function, immunological
      investigations, the use of the bronchoalveolar lavage, the prognostic and
      management of HP are discussed.

PMID- 11584681
TI  - The flexible bronchoscopic approach to lung volume reduction.
AB  - Surgical lung volume reduction is effective in patients with chronic obstructive
      pulmonary disease (COPD) because it improves the ratio between residual lung
      volume and total lung volume. The same effect may be achieved by inducing an
      iatrogenic atelectasis in one or more lung lobes using a flexible bronchoscopic
      approach. This article discusses the origin and the progress, up to date, of this
      new minimally invasive flexible bronchoscopic approach.

PMID- 11584682
TI  - [Alcohol polyneuropathy].
AB  - The Alcoholic Polyneuropathy occurs in about 10-30% of alcoholics. It is the
      second most frequent type of polyneuropathies after the diabetic form. The
      clinical pattern is a symmetric sensory or symmetric motor sensory manifestation
      type. In almost all cases there is a pressure pain of the calves. In the
      beginning the disturbance of the proprioceptive sensation is predominant.
      Disturbances of the autonomic nervous system deal with the sympathetic as well as
      the parasympathetic nervous system. Morphologically there is a primary axonal
      degeneration. A direct toxic influence of the alcohol itself is discussed as the
      prevailing pathomechanism.

PMID- 11584683
TI  - [Prerequisites, indications and contraindications of IV-lysis of ischemic stroke
      with rt-PA].
AB  - BACKGROUND AND PURPOSE: To evaluate prerequisites, safety, and efficacy of i.v.
      thrombolysis of ischemic stroke with rtPA in an academic medical center. METHODS:
      Over a period of 2 years and 10 months all patients admitted with a diagnosis of
      stroke were recruited. Inclusion and exclusion criteria for i.v.-thrombolysis
      were combined from large scale randomized controlled trials, the time window,
      however, could be extended up to 4 hours in subjects with a negative CT-scan.
      Prespecified outcome parameters were the modified Rankin Scale (mRS) and the
      Barthel Index (BI) at 3 months, and symptomatic hemorrhagic complications.
      Additionally, time parameters, such as onset-admission-time, door-Ct-time, door
      needle time, and onset-needle time were recorded. RESULTS: During the reported
      period 103 patients underwent i.v.-thrombolysis, corresponding to 14.9% of all
      patients with ischemic stroke, and 47% of patients with ischemic stroke arriving
      in < 3 hours after symptom onset. The mean baseline NIHSS was 14, the mean mRS 13
      (3-34), the mean age 70 (+/- 12) years. The following time intervals were
      observed: Onset-admission-time 64 min., door-CT-time 27 min., admission-needle
      time 80 min., and onset-needle-time 142 min. There were 4 symptomatic
      intracerebral hemorrhagic transformations, including 3 parenchymal hemorrhages, 2
      of them lethal, and one with almost full recovery. According to the mRS, 39% of
      patients had a good (mRS 0-1), 72% a good to moderate recovery (mRS 0-2). The
      corresponding figures for the BI were 60% BI 95-100 and 72% BI > 90. The
      mortality was 15%. CONCLUSION: The i.v.-thrombolysis of ischemic stroke with rt
      PA demands appropriate organisation of the pre- and in-hospital phase and can be
      performed safely and efficaciously in daily clinical routine if inclusion and
      exclusion criteria as well as all safety measures during the critical phase after
      therapy are strictly obeyed.

PMID- 11584684
TI  - [Pathological laughing and crying].
AB  - The classic literature on pathological laughter and crying emphasizes the
      difference between incontinence and lability of affect. Pathological laughter and
      crying as key symptoms of affect incontinence are viewed as the effects of
      disinhibition of motor synergisms without congruent affect, which is the crucial
      difference to affect lability. The interpretation as a disinhibitory phenomenon
      is supported by clinical and electromyographic observations, which found a lack
      of modulation of intensity in pathological laughter and crying. In 1924, Wilson
      postulated a supranuclear pontobulbar center for affective synergisms that is
      controlled by cortex and thalamus. Accordingly, Kleist viewed a combined lesion
      of thalamic or brainstem structures and corticofugal motor projection systems as
      the pathoanatomic basis of affect incontinence. Recent work reported the frequent
      occurrence of affect incontinence with stroke and dementia of the Alzheimer type
      and thus disagrees with the classical theory. However, the methods used cannot
      rule out a confounding between affect lability and incontinence.

PMID- 11584685
TI  - [Controlled dynamic weight training in patients with neuromuscular disorders].
AB  - The question posed was whether individually adapted, controlled dynamic weight
      training, in accordance with training principles and methods from sports science,
      applied for a limited time, can lead to an improvement in the stimulation and
      release of muscular strength in patients with neuromuscular disorders. The
      muscles of the pelvic girdle and the lower extremity of 10 patients (5 with
      dystrophic muscle disease and 5 with neurogenic muscular atrophy) were exercised
      provisionally for a period of 6 weeks on various weight training machines. The
      training routine was 3 sessions (TS) per week at an intensity range of 40-60% of
      the respective best performance for the exercise (One Repetition Maximum; ORM),
      at 8-12 repetitions/set and 2-4 sets/exercise. Body weight and ORM were
      determined before, during and after the training period (TP), the different load
      criteria/TS were documented. It was possible to train the patients in accordance
      with principles of training known from sports science. Over the entire TP it was
      possible to increase the load criteria significantly (p < 0.01). The ORM had
      increased considerably in all exercises after the TP (p < 0.01). The changes in
      strength lay between 11 and 95%. Correlation analyses demonstrated that the
      percentage changes in strength correlated significantly (p < 0.01) and positively
      (r = 0.87) with the training load in terms of quality. No significant changes in
      development of strength could be ascertained between the two groups of patients
      (dystrophic versus atrophic). The individually adjusted, controlled dynamic
      weight training described above, leads to an increase in the stimulation and
      release of strength and can be conducted according to principles of training
      science. Applied in clinical rehabilitation, it represents a supplementary form
      of therapy in the symptomatic treatment of neuromuscular disorders.

PMID- 11584686
TI  - [Cannabis consumption and its psychosocial effects in a comparison of different
      cultures].
AB  - Cannabis consumption is a social and cultural phenomenon. It has a specific place
      in each society, therefore psychotropic effects are judged differently. In
      medieval Islam cannabis consumption showed connections with religious and mystic
      events and was basically formed through consuming sufis. The main risk of
      cannabis use was especially the induction of "madness" or psychotic states in
      case of high dosage and high frequency of consumption. Nevertheless there were no
      social sanctions. Today in western civilized countries cannabis consumption is
      connected with relaxed activity and is mainly consumed by adolescents. The main
      risk is seen in the ongoing consumption of illicit drugs, since cannabis
      consumption is widely held as the first step for such a career. On the other hand
      the induction of psychotic states or a schizophrenia-like psychosis is rarely
      named in public discussions. At all times self-reports of cannabis-users named
      creative aspects of cannabis-consumption, normally seen in the conscious
      translation into normal reality of astonishing and formerly unknown experiences
      made in an intoxicated state. This aspect of cannabis use is widely disregarded
      in scientific research. Various reasons therefore are discussed.

PMID- 11584687
TI  - [Short- and medium-term outcome of outpatient treatment of alcohol dependent
      patients. A 6-, 18- and 36-month follow-up].
AB  - The aim of this study was to investigate the short- and medium-term outcome of
      alcohol dependent patients in Germany after a one-year outpatient treatment. For
      this purpose, a 6-, 18- and 36-month follow-up of 97 socially well adapted
      alcohol dependent patients treated between 1992 and 1997 at three "psychosocial
      advice center" run by the Diakonie Wurttemberg, Germany, was carried out. Based
      on the time period between treatment and follow-up, all 97 patients could be
      followed up for 6 months, 71 for 18 months, and 33 for 36 months. 83% of patients
      could be interviewed at 6 months, 80% at 18 months, and 78% at 36 months. The
      statistical analyses were based on the "intention to treat" model. All patients
      treated between 1992 and 1997 were included. Patients for whom no information was
      available were classified as relapsers. 6 months after the outpatient treatment
      59% of patients were abstinent, 4% had lapsed and 37% were relapsers. At the 18-
      and 36-month follow-ups 61% of patients had been abstinent in the 6 months before
      the interview. 53% and 39% of patients respectively were continuously abstinent
      over the entire follow-up period of 18 and 36 months. Prognostic criteria for a
      relapse were regular completion of treatment (p < 0.001) and no prior
      detoxification or abstinence oriented treatment (p < 0.01). Patients without a
      partner showed a tendency towards higher relapse rates (p < 0.10). The results of
      this study indicate that an outpatient treatment program can be as effective as
      inpatient or combined inpatient/outpatient treatments, at least for some patients
      with good social integration.

PMID- 11584688
TI  - [Personality disorders and psychiatric comorbidity in obsessive-compulsive
      disorder and anorexia nervosa].
AB  - The aim of this prospective longitudinal study was to examine the course of
      adolescent anorexia nervosa and obsessive-compulsive disorder (OCD) (fulfilling
      DSM-III-R criteria) to compare psychiatric comorbidity and personality disorders
      of both groups. Because anorexia nervosa patients are mainly female, we compared
      them only with female OCD patients. Ten years after discharge the whole sample
      (32 female patients; 100%) of a group of 39 (32 female; 7 male) anorexia nervosa
      patients could be reexamined personally. 25 (61%) female patients of a group of
      116 patients (41 female; 75 male) with obsessive-compulsive disorder were also
      reexamined. The anorexia nervosa patients were interviewed using the Structured
      Interview for Anorexia and Bulimia nervosa (SIAB [39]) to assess eating disorder
      symptomatology. To examine comorbid psychiatric disorders we used the Composite
      International Diagnostic Interview, WHO [44] and SCID-II [45] for personality
      disorders. One fourth of the patients with anorexia nervosa (AN) and 20% of the
      patients with obsessive-compulsive disorder had a personality disorder according
      to DSM-III-R. Most of them were "Cluster C"-personality disorders (AN: 28%; OCD:
      20%). In the group of the female OCD patients 8% schizoid, 4% schizotype and 12%
      paranoid personality disorders were observed. The most prevalent psychiatric
      disorders were anxiety (AN: 28%; OCD: 20%) and affective disorders (AN: 16%; OCD:
      16%). Our results support the view that in the course of anorexia nervosa and in
      obsessive-compulsive disorder there is a high prevalence of psychiatric
      comorbidity and "Cluster C"-personality disorders according to DSM-III-R. These
      results might confirm a model of a high vulnerability of the serotonergic
      neurotransmitter system in patients with anorexia nervosa or OCD.

PMID- 11584689
TI  - Who did what? The human side of the science enterprise.

PMID- 11584690
TI  - Hepatitis C: an update.
AB  - Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver
      cirrhosis, and hepatocellular carcinoma worldwide. While current therapeutic
      options for hepatitis C are limited, recent progress in the understanding of the
      biology of HCV led to the identification of novel targets for antiviral
      intervention. In addition, molecular and immunotherapeutic strategies to inhibit
      HCV replication or gene expression and to enhance the cellular immune response
      against HCV are being explored. These and other novel antiviral strategies may
      eventually complement existing therapeutic modalities. Here, we briefly review
      current concepts of the epidemiology, molecular virology, pathogenesis, natural
      history, diagnosis, therapy, and prevention of hepatitis C.

PMID- 11584691
TI  - The controversial early history of cyclosporin.
AB  - The biological effects of cyclosporin, namely immunosuppression and absence of
      cytotoxicity, were discovered-in the course of a general screening program in
      which many scientists at Sandoz were involved. Contrary to some statements in the
      literature both Dr J. Borel and Dr H. Stahelin markedly contributed to the
      discovery and characterisation of the biological profile of the drug. In its
      subsequent exploitation Borel played the leading role. The outstanding clinical
      importance and the extraordinary commercial success of cyclosporin explain the
      widespread interest in the history of its discovery and development. It is also
      understandable that the recollection of the events by the individuals involved in
      the early phases of this history is influenced by subjective impressions and
      interpretations, which do not always reflect the historical facts. It is the
      purpose of this report to record and interpret the facts as accurately and as
      completely as possible on the basis of the available records.

PMID- 11584692
TI  - Economic and clinical impact of alternative disease management strategies for
      secondary prevention in type 2 diabetes in the Swiss setting.
AB  - PRINCIPLES: Different intervention strategies for the optimisation of disease
      management of diabetes exist and have been shown to increase the proportion of
      patients receiving screening and examinations and to improve risk factors such as
      HbA1c, lipids, and blood pressure. Thus, in the long-term, a decrease in diabetic
      complications and the associated costs could be expected. To address this
      question, the current analysis used a published diabetes simulation model to
      analyse the long-term clinical and economic implications of implementing various
      interventions in the Swiss setting. METHODS: Based on data from the literature,
      the short-term effects on clinical variables of multifactorial interventions,
      including screening for nephropathy and retinopathy, educational programmes and
      control of cardiovascular risk profile were assessed, and a cost-effectiveness
      analysis in comparison to standard care was performed. Life expectancy (LE) and
      total lifetime costs (TC) from the perspective of the health insurance payer were
      calculated using a long-term Markov simulation model. RESULTS: The multifactorial
      intervention led to an improvement in undiscounted LE of 0.56 years (LE = 10.73
      and 11.29 years for standard care and multifactorial intervention respectively),
      and a reduction in 3%-discounted TC of CHF 7313 (10.7%) per patient compared to
      current standard practice. Extrapolation to the whole Swiss type 2 diabetes
      population (285,000) showed yearly cost savings of CHF 194 million from the
      multifactorial intervention. CONCLUSIONS: The implementation of multifactorial
      interventions, including improved control of cardiovascular risk factors,
      combined with early diagnosis and treatment of diabetic complications, could be
      both cost- and life-saving in the Swiss setting.

PMID- 11584693
TI  - Screening mammographies in Switzerland: what makes female and male physicians
      prescribe them?
AB  - QUESTION UNDER STUDY: Physicians play a key role in motivating women to undergo
      mammography screening. In 1998 we assessed Swiss physicians' attitudes to
      mammography screening and their prescription behaviour in this regard. METHODS:
      All female physicians and every second male physician aged 50-69 who were either
      not board-certified or board-certified in general practice, internal medicine, or
      obstetrics/gynaecology were sent a questionnaire. The response rate was 50% and
      thus 738 questionnaires were included in this study. Of the study population 39%
      were female and 61% male physicians. The distribution of professional backgrounds
      was: 27% board-certified general practitioners; 23% board-certified internists;
      11% board-certified gynaecologists; 39% not board-certified. RESULTS: 55% of all
      study participants were in favour of a mammography screening programme for women
      aged over 50 in Switzerland, but breast self-examination and clinical breast
      examination were judged to have a more positive impact on breast cancer survival.
      Among clinically practising physicians, 22% reported generally prescribing
      biannual screening mammographies for women aged 50-69. Irrespective of other
      determinants, physicians from the Italian- and French-speaking parts of
      Switzerland prescribed screening mammographies more often than their colleagues
      from the German-speaking part (odds ratio [OR] 2.5; 95% confidence interval [CI]
      1.5-4.2). Clinical practice in obstetrics/gynaecology (OR 2.4; CI 1.3-4.2) and a
      self-reported high level of knowledge concerning mammography screening (OR 1.9;
      CI 1.1-3.2) were also positively associated with the prescription of screening
      mammography. CONCLUSIONS: Since mammography screening programmes exist in only
      three French-speaking cantons of Switzerland (VS; VD; GE), the gap in
      prescription of screening mammographies between French/Italian- and German
      speaking regions must be narrowed to prevent a higher prevalence of side effects
      from opportunistic screening among German-speaking women. There is a need to
      educate physicians and the political community regarding the risks and benefits
      of mammography screening.

PMID- 11584694
TI  - A case of transfusion transmitted malaria in Switzerland.

PMID- 11584695
TI  - Integration crossroads.

PMID- 11584696
TI  - Laying the foundation.

PMID- 11584697
TI  - Collaboration, Internet style.

PMID- 11584698
TI  - Comorbidity and DM.

PMID- 11584699
TI  - Mining the gems.

PMID- 11584700
TI  - When once isn't enough.

PMID- 11584701
TI  - HIPAA and MCOs: administrative simplification or IT modernization?

PMID- 11584702
TI  - The world at bedside.

PMID- 11584703
TI  - Information where it's needed.

PMID- 11584704
TI  - What works. Documented savings.

PMID- 11584705
TI  - What works. For your files.

PMID- 11584706
TI  - Practice management HotList.

PMID- 11584707
TI  - Preventing fraud.

PMID- 11584708
TI  - Healthcare's fast future.

PMID- 11584709
TI  - The old cancer patient.

PMID- 11584710
TI  - [Treatment of malignant non-Hodgkin's lymphomas in elderly patients].
AB  - The number of elderly patients with non-Hodgkin's lymphomas (NHL) is continuously
      increasing. The diagnostic and staging procedures should be carried out in
      elderly patients as careful as in younger patients. Furthermore, for treatment
      decisions geriatric assessment and the patient's preferences concerning therapy
      are essential and have to be considered. The treatment of indolent NHL depends on
      the stage of the disease and the clinical status of the patient. Most of the
      patients with limited indolent NHL can be treated with curative intent using
      localized irradiation. Treatment of patients with advanced indolent NHL is
      palliative. In contrast, all stages of aggressive NHL can also be treated with
      curative intent in elderly patients. In limited aggressive NHL standard treatment
      consists of polychemotherapy followed by involved field irradiation. Standard
      treatment of advanced aggressive NHL is polychemotherapy with cyclophosphamide,
      adriamycin, vincristine and prednisone (CHOP). The goal for the near future is to
      improve perspectives for elderly patients with NHL. One way is to treat as many
      of these patients as possible according to current standards. In the field of
      geriatric oncology, one of the questions we are often confronted with is the
      limitation of treatment, especially in frail patients. This issue is closely
      associated with ethical considerations which are discussed in another paper.

PMID- 11584711
TI  - [Therapy of acute myeloid leukemia in the elderly patient].
AB  - Incidence and mortality rates of acute myeloid leukemia (AML) increase
      exponentially with advancing age. AML diagnosed in elderly patients differs from
      that diagnosed in younger patients. But not only disease-specific differences are
      important. Treating elderly patients with AML age-associated differences in the
      patients general presentation, such as physiological changes in organ function,
      decreased ability to react to stress, dependence in activities of daily living,
      existence of other morbidities (co-morbidity), the need to take drugs for those
      diseases and the reduced life expectancy can force alterations in the disease
      management. Clinical trials for the treatment of AML have been excluding elderly
      patients for years. Even trials accepting elderly patients with AML did select
      the group of otherwise healthy elderly patients for participation in the trial.
      Thus the data for AML management in elderly patients do not reflect the whole
      group of elderly patients with AML. If the patient is treated with curative
      intention, therapy of choice is the so-called 3 + 7 protocol for induction of
      complete remission, followed by a consolidation therapy and in some cases by
      maintenance therapy. In some situations, especially in very old patients, a
      palliative intention to treatment is favored. There are no generally accepted
      criteria to measure treatment benefit in this setting nor established
      chemotherapy protocols for this situation. Further trials for elderly patients
      with AML have to offer treatment options for the whole group of patients and have
      to determine what treatment approach is the best for which individual patient.

PMID- 11584712
TI  - [Chemotherapy of non-small-cell bronchial carcinoma in elderly patients].
AB  - The incidence of lung cancer increases with age, and non-small-cell histotypes
      account for approximately 85% of lung cancers in patients aged older than 65
      years. Results of large multicentric trials provide no evidence that elderly lung
      cancer patients who receive systemic chemotherapy have a worse outcome than
      younger patients. There is, however, an underrepresentation of older patients in
      cancer treatment trials, at least in part due to the stringent eligibility
      criteria of these trials. Recent studies specifically designed for elderly
      patients with advanced non-small-cell lung cancer have shown that chemotherapy
      improves survival and disease-related symptoms also in this age group. However,
      the degree of comorbidity was found to affect both the tolerance to treatment and
      the survival outcome.

PMID- 11584713
TI  - [Conceptual and ethical questions in geriatric oncology].
AB  - Geriatric oncology concentrates on the field of cancer in the expanding aging
      population. Therapeutic goals are based on individual risk-assessment,
      comorbidities, and the specific tumor-biology. Good management of older cancer
      patients requires a multidimensional risk profile. Shared decision-making in
      geriatric oncology has to recognize a sometimes impaired autonomy. Possible
      conflicts between beneficence and autonomy are discussed and specific problems of
      the elderly patients are given. Informed consent requires competence, which might
      be lacking to some degree. It is the task of a responsible physician to promote
      autonomous decision-making as far as possible.

PMID- 11584714
TI  - [Social aid and need for nursing care: an analysis of fulfilled and failed goals
      in regulatory health nursing care insurance after 5 years].

PMID- 11584715
TI  - [Determinants of psychotropic drug utilization in homes for the elderly and in
      nursing homes].
AB  - A large proportion of the residential and nursing home population is mentally
      ill. The causes for increased prescription of psychotropic drugs other than
      mental disorders have been discussed. This study presents data on the role of the
      individual's characteristics and institutional conditions on psychotropic drug
      use in residents of residential and nursing homes. Therefore the psychotropic
      drug use of 4 old-people's homes in Leipzig (Germany) was reviewed.
      Sociodemographic characteristics and a number of behavioral patterns of the
      residents were examined. Regression analysis revealed associations of age, gender
      and certain behavioral patterns (e.g., agitation, insomnia with nightly
      disturbances) and psychotropic drug use. Beyond that, psychotropic drug use
      varied among the 4 institutions' practices. Further research should be aimed at
      gaining insight into the interplay of these individual and institutional
      influences on psychotropic drug use in order to develop specific interventions to
      optimize treatment.

PMID- 11584716
TI  - [Significance of body weight status for bone density in the elderly and very
      old].
AB  - Reduced bone density and osteoporosis are significant health problems and
      contributors to disability and mortality among older women and men. Therefore the
      decline of bone mineral content (BMC) and bone mineral density (BMD) are aspects
      of ageing with great medical and social significance. In recent years a low body
      weight was declared to be an important risk factor for the development of
      osteoporosis. In the present study the impact of weight status, defined by the
      categories of the WHO, on BMC of the whole body and BMD of the proximal femur
      end, determined by dual energy x-ray absorptiometry (DEXA), were studied in 77
      female and 62 male probands aged between 60 and 92 years (x = 71.7 yrs). With
      increasing weight status (BMI categories), BMC and BMD increased significantly (p
      < 0.001). This was true of both sexes. Even moderate overweight women and men
      (BMI 25.0-29.99) showed a significantly higher bone density than their normal
      weight counterparts (BMI < 25.0). In the present study a marked positive impact
      of body weight on bone density of old-aged women and men could be shown.

PMID- 11584717
TI  - [Social environment and social network: extent and resources of the daily life of
      elderly persons].
AB  - The study asks for factors determining the activity space of the aged. Indicators
      of old people's activities space are the number of their outdoor activities and
      their use of the local supply of public facilities. Controversial hypothesis are
      won from ecological gerontology and psychological attachment theory. At issue in
      the first place is how personal social networks mold older people's outdoor
      behavior. Another hypothesis assumes social support of the elderly to be exposed
      to the laws of reciprocity. The study makes use of a poll titled "life
      organization of older people" that was conducted by the German Youth Institute in
      1993. Respondents were German 55- to 79-year-olds (N = 4130). Analyses rely on
      multifactorial analyses of variance. Results back attachment theory and the
      reciprocity thesis.

PMID- 11584718
TI  - [Interdisciplinary management of vasculitis patients: internist/rheumatologist].
AB  - Systemic vasculitides (SV) represent a heterogeneous group of different entities
      with varying clinical and pathological-anatomical characteristics that physicians
      of diverse disciplines are involved in the treatment of patients with SV. At the
      onset of disease organ manifestations often present as a single symptom without
      appearance of indirect signs of vasculitides as musculoskeletal complaints and
      constitutional symptoms indicating inflammatory systemic disease. Therefore early
      interdisciplinary care is extremely important to avoid major organ involvement
      with the development of fatal disease. Besides the multidisciplinary physical
      examination serological and immunological parameters, particularly in small
      vessel vasculitides are relevant in establishing the diagnosis. Regarding the
      interdisciplinary care we differentiate between primary diagnostic procedures and
      continuous follow-up to observe therapeutic and side effects of medications.
      Instruments for the assessment of disease extent (DEI), activity (BVAS) and
      irreversible damage (VDI) were developed in recent years to document
      prospectively the disease status and support activity-adjusted treatment. Because
      of the chronic relapsing character of systemic vasculitides, the measurement of
      health-related quality of life gained progressive interest in the longitudinal
      follow-up. In addition in these rare diseases early patient education with
      information on the disease, treatment, side effects and training in self
      management strategies will enable patients to actively participate in the
      management of their disease and bear responsibility.

PMID- 11584719
TI  - [Manifestations of primary vasculitis in the ENT region].
AB  - The primary ANCA associated vasculitides, Wegener's granulomatosis (WG), Churg
      Strauss syndrome (CSS) and microscopic polyangiitis (MPA), frequently affect the
      ENT region. For several reasons WG is of special significance for the
      otorhinolaryngologist. First, disease activity limited to the upper respiratory
      tract (localized WG) often proceeds the systemic vasculitis (generalized WG). The
      early diagnosis therefore has decisive consequences for stage adapted therapy.
      Second, in most cases (nearly 80%) WG is diagnosed histologically on biopsy
      specimens from the ENT region. During the initial phase of WG this is of
      diagnostic relevance, because at this stage the serologic parameters (acute-phase
      proteins) usually have a normal value and PR3-ANCA is (still) negative in 2/3 of
      the patients. Third, in many cases recurrences reveal increased activity in the
      ENT region, or start in this area. Clinically in most cases chronic
      rhinosinusitis with crusting and epistaxis is seen, sometimes with septal
      perforation and/or saddle nose. Apart from this there are often unclear middle
      ear symptoms with recurrent effusions and the inner ear is sometimes also
      affected. Laryngeal manifestations are typically located in the subglottic area
      and lead to subglottic stenosis. In the differential diagnosis, diseases in which
      epitheloid cell granulomas occur, such as sarcoidosis and TBC, need to be
      considered, but also foreign body granulomas and fungus diseases. Finally
      malignant tumours, especially malignant lymphomas, have to be ruled out.

PMID- 11584720
TI  - [Ophthalmological diagnosis in systemic vasculitis].
AB  - Ocular manifestations of systemic vasculitides are extraordinarily pleomorph and
      have been described for many decades. In the introduction the special interaction
      of the immune system and the eye is outlined. Thereafter diagnostic procedures of
      patients suffering from systemic vasculitides are shown from an ophthalmological
      view point. Many examples, which show multiple possibilities of ocular
      manifestations on systemic vasculitides, are given. With regard to the anatomy of
      the eye, a review is given on the involvement of the 1) outer eye and a tear
      film, 2) lacrimal duct diseases, 3) diseases of the lid, 4) diseases of
      conjunctiva, 5) diseases of sclera, 6) diseases of the cornea, 7) diseases of the
      lens, 8) intraocular inflammation, 9) retinal affections, 10) optic nerve
      inflammation, and 11) orbiota involvement. Frequencies of these structures
      involved in the various systemic vasculitides are outlined. Principally every
      systemic vasculitis can induce every eye manifestation; however, larger patient
      groups show characteristic features of eye manifestations in systemic
      vasculitides. Special reference is given to Wegener's granulomatosis, giant-cell
      arteritis and Behcet vasculitis.

PMID- 11584721
TI  - [Vasculitis--interdisciplinary diagnosis: radiology].
AB  - Determination of disease extension and disease activity are in the foreground of
      diagnostic imaging in vasculitides. There are several radiologic modalities
      available each having specific indications. Magnetic resonance imaging (MRI)
      readily depicts granulomas and mucosal inflammations in the paranasal sinuses,
      nasal cavity and orbits. Computed tomography detects osseous lesions of the
      skull. Due to its superb sensitivity MRI is an established screening modality for
      CNS vasculitides, although there are limitations with regard to specificity. In
      spite of its limited accuracy in most institutions angiography is still required
      for radiological confirmation of CNS vasculitis. Perfusion and diffusion MR
      imaging may combine the advantages of 'conventional' MRI and angiography. By now
      the method is not fully validated for vasculitides, however. Vascular disease in
      Takayasu's arteritis and in giant cell arteritis involving predominantly large
      and medium sized vessels is readily diagnosed by non invasive magnetic resonance
      angiography. Percutaneous transluminal angioplasty has proven to be an effective
      and save therapeutic modality for the cure of vascular stenoses and occlusions.
      Plain film radiography in two planes is the established modality for pulmonary
      imaging. In pulmonary vasculitides a more thorough analysis of lung disease is
      provided by high resolution computed tomography. Diagnostic imaging does
      substantially assist in the interdisciplinary management of patients suffering
      from vasculitides.

PMID- 11584722
TI  - [Presentation of the Lubeck/Bad Bramstedt Competence Center].

PMID- 11584723
TI  - [Rare association of acute febrile neutrophilic dermatosis (Sweet syndrome) with
      rheumatoid arthritis].
AB  - We report on a 57 year old women with a long-standing course of severe rheumatoid
      arthritis, developing acute febrile neutrophilic dermatosis (Sweet's syndrome) in
      an active phase of the arthritis. Sweet's syndrome has been reported with
      hematologic and solid malignancies, infections and several autoimmunopathies, but
      in only three cases is there a coincidence with rheumatoid arthritis. We review
      Sweet's syndrome with regard to pathogenesis and associated disorders.

PMID- 11584724
TI  - Number needed to kill. Individual drug risk with NSAIDs.

PMID- 11584725
TI  - [Comment on the contribution by G. Keyser, "Are there reliable dietary
      recommendations for patients with rheumatoid arthritis?"].

PMID- 11584726
TI  - Globalization: from rhetoric to evidence.

PMID- 11584727
TI  - The etiology of maternal mortality in developing countries: what do verbal
      autopsies tell us?
AB  - OBJECTIVE: To reassess the practical value of verbal autopsy data, which, in the
      absence of more definitive information, have been used to describe the causes of
      maternal mortality and to identify priorities in programmes intended to save
      women's lives in developing countries. METHODS: We reanalysed verbal autopsy data
      from a study of 145 maternal deaths that occurred in Guerrero, Queretaro and San
      Luis Potosi, Mexico, in 1995, taking into account other causes of death and the
      WHO classification system. The results were also compared with information given
      on imperfect death certificates. FINDINGS: The reclassification showed wide
      variations in the attribution of maternal deaths to single specific medical
      causes. CONCLUSION: The verbal autopsy methodology has inherent limitations as a
      means of obtaining histories of medical events. At best it may reconfirm the
      knowledge that mortality among poor women with little access to medical care is
      higher than that among wealthier women who have better access to such care.

PMID- 11584728
TI  - Comparison of safety and immunogenicity of a Vi polysaccharide typhoid vaccine
      with a whole-cell killed vaccine in Malaysian Air Force recruits.
AB  - OBJECTIVE: To carry out a comparative study of the safety and immunogenicity of
      Vi polysaccharide vaccine against whole-cell killed (WCK) typhoid vaccine.
      METHODS: The study was carried out on young adult recruits (aged 18-25 years) of
      the Malaysian Air Force. A total of 125 subjects received the Vi polysaccharide
      vaccine and 114 received the WCK vaccine. FINDINGS: The Vi vaccine was
      significantly less reactogenic than the WCK vaccine with regard to systemic and
      local reactions. Following administration of the Vi vaccine, seroconversion rates
      (defined as the percentage of subjects with a 4-fold rise of baseline antibody
      level) of 75.5% and 67% were observed at 2 weeks and 6 weeks, respectively, after
      immunization, compared with 25% and 31.3% among recipients of the WCK vaccine. Of
      the 110 Vi vaccinees with serological data, 21 (19%) had high, seroprotective,
      pre-immunization levels of anti-Vi antibodies (> or = 1 microgram/ml). The
      majority of subjects in this group came from a region in Malaysia which is known
      to have high typhoid endemicity. Interestingly, these antibody levels were
      boosted considerably following administration of vaccine at a level that was 5
      fold higher than in subjects with low pre-immunization levels. In contrast, the
      seroconversion rates in those receiving the Vi vaccine were higher in subjects
      with low pre-immunization levels of anti-Vi antibodies (76-84%), compared to
      those with protective levels of > or = 1 microgram/ml prior to immunization (48
      57%). CONCLUSIONS: The study reaffirms the safety and efficacy of the Vi
      polysaccharide vaccine and identifies a hitherto unrecognized advantage in its
      use, i.e. it is a potent immunogen that boosted considerably the protective
      antibody levels among a significant number of immunologically sensitized
      individuals living in typhoid-endemic regions.

PMID- 11584729
TI  - Eradicating chancroid.
AB  - Genital ulcers are important cofactors of HIV transmission in the countries most
      severely affected by HIV/AIDS. Chancroid is a common cause of genital ulcer in
      all 18 countries where adult HIV prevalence surpasses 8% and is rare in countries
      with low-level HIV epidemics. Haemophilus ducreyi, the causative organism of
      chancroid, is biologically vulnerable and occupies a precarious epidemiological
      niche. Both simple, topical hygiene and male circumcision greatly reduce risk of
      infection and several classes of antibiotics--some of which can be administered
      in single-dose treatment regimens--provide rapid cure. H. ducreyi depends on
      sexual networks with high rates of partner change for its survival, thriving in
      environments characterized by male mobility and intensive commercial sex
      activity. Elimination of H. ducreyi infection from vulnerable groups results in
      disappearance of chancroid from the larger community. Once endemic in Europe and
      North America, chancroid began a steady decline early in the twentieth century,
      well before the discovery of antibiotics. Social changes--resulting in changing
      patterns of commercial sex--probably disrupted the conditions needed to sustain
      chancroid as an endemic disease. Sporadic outbreaks are now easily controlled
      when effective curative and preventive services are made available to sex workers
      and their clients. More recently, chancroid prevalence has declined markedly in
      countries such as the Philippines. Senegal, and Thailand, a development that may
      contribute to stabilization of the HIV epidemics in these countries. Eradication
      of chancroid is a feasible public health objective. Protecting sex workers and
      their clients from exposure to sexually transmitted diseases (STDs) and improving
      curative services for STDs are among the proven strategies that could be
      employed.

PMID- 11584730
TI  - Is globalization good for your health?
AB  - Four points are made about globalization and health. First, economic integration
      is a powerful force for raising the incomes of poor countries. In the past 20
      years several large developing countries have opened up to trade and investment,
      and they are growing well--faster than the rich countries. Second, there is no
      tendency for income inequality to increase in countries that open up. The higher
      growth that accompanies globalization in developing countries generally benefits
      poor people. Since there is a large literature linking income of the poor to
      health status, we can be reasonably confident that globalization has indirect
      positive effects on nutrition, infant mortality and other health issues related
      to income. Third, economic integration can obviously have adverse health effects
      as well: the transmission of AIDS through migration and travel is a dramatic
      recent example. However, both relatively closed and relatively open developing
      countries have severe AIDS problems. The practical solution lies in health
      policies, not in policies on economic integration. Likewise, free trade in
      tobacco will lead to increased smoking unless health-motivated disincentives are
      put in place. Global integration requires supporting institutions and policies.
      Fourth, the international architecture can be improved so that it is more
      beneficial to poor countries. For example, with regard to intellectual property
      rights, it may be practical for pharmaceutical innovators to choose to have
      intellectual property rights in either rich country markets or poor country ones,
      but not both. In this way incentives could be strong for research on diseases in
      both rich and poor countries.

PMID- 11584731
TI  - Globalization and health: results and options.
AB  - The last two decades have witnessed the emergence and consolidation of an
      economic paradigm which emphasizes domestic deregulation and the removal of
      barriers to international trade and finance. If properly managed, such an
      approach can lead to perceptible gains in health status. Where markets are non
      exclusionary, regulatory institutions strong and safety nets in place,
      globalization enhances the performance of countries with a good human and
      physical infrastructure but narrow domestic markets. Health gains in China, Costa
      Rica, the East Asian "tiger economies" and Viet Nam can be attributed in part to
      their growing access to global markets, savings and technology. However, for most
      of the remaining countries, many of them in Africa, Latin America and Eastern
      Europe, globalization has not lived up to its promises due to a combination of
      poor domestic conditions, an unequal distribution of foreign investments and the
      imposition of new conditions further limiting the access of their exports to the
      OECD markets. In these developing countries, the last twenty years have brought
      about a slow, unstable and unequal pattern of growth and stagnation in health
      indicators. Autarky is not the answer to this situation, but neither is
      premature, unconditional and unselective globalization. Further unilateral
      liberalization is unlikely to help them to improve their economic performance and
      health conditions. For them, a gradual and selective integration into the world
      economy linked to the removal of asymmetries in global markets and to the
      creation of democratic institutions of global governance is preferable to instant
      globalization.

PMID- 11584732
TI  - The globalization of public health: the first 100 years of international health
      diplomacy.
AB  - Global threats to public health in the 19th century sparked the development of
      international health diplomacy. Many international regimes on public health
      issues were created between the mid-19th and mid-20th centuries. The present
      article analyses the global risks in this field and the international legal
      responses to them between 1851 and 1951, and explores the lessons from the first
      century of international health diplomacy of relevance to contemporary efforts to
      deal with the globalization of public health.

PMID- 11584733
TI  - Information and communication technologies and health in low income countries:
      the potential and the constraints.
AB  - This paper outlines the potential offered by technological progress in the
      information and communication technologies (ICTs) industries for the health
      sector in developing countries, presents some examples of positive experiences in
      India, and considers the difficulties in achieving this potential. The
      development of ICTs can bring about improvements in health in developing
      countries in at least three ways: as an instrument for continuing education they
      enable health workers to be informed of and trained in advances in knowledge;
      they can improve the delivery of health and disaster management services to poor
      and remote locations; and they can increase the transparency and efficiency of
      governance, which should, in turn, improve the availability and delivery of
      publicly provided health services. These potential benefits of ICTs do not
      necessarily require all the final beneficiaries to be reached directly, thus the
      cost of a given quantum of effect is reduced. Some current experiments in India,
      such as the use of Personal Digital Assistants by rural health workers in
      Rajasthan, the disaster management project in Maharashtra and the computerized
      village offices in Andhra Pradesh and Pondicherry, suggest creative ways of using
      ICTs to improve the health conditions of local people. However, the basic
      difficulties encountered in using ICTs for such purposes are: an inadequate
      physical infrastructure; insufficient access by the majority of the population to
      the hardware; and a lack of the requisite skills for using them. We highlight the
      substantial cost involved in providing wider access, and the problem of resource
      allocation in poor countries where basic infrastructure for health and education
      is still lacking. Educating health professionals in the possible uses of ICTs,
      and providing them with access and "connectivity", would in turn spread the
      benefits to a much wider set of final beneficiaries and might help reduce the
      digital divide.

PMID- 11584734
TI  - Globalization, diet, and health: an example from Tonga.
AB  - The increased flow of goods, people, and ideas associated with globalization have
      contributed to an increase in noncommunicable diseases in much of the world. One
      response has been to encourage lifestyle changes with educational programmes,
      thus controlling the lifestyle-related disease. Key assumptions with this
      approach are that people's food preferences are linked to their consumption
      patterns, and that consumption patterns can be transformed through educational
      initiatives. To investigate these assumptions, and policies that derive from it,
      we undertook a broad-based survey of food-related issues in the Kingdom of Tonga
      using a questionnaire. Data on the relationships between food preferences,
      perception of nutritional value, and frequency of consumption were gathered for
      both traditional and imported foods. The results show that the consumption of
      health-compromising imported foods was unrelated either to food preferences or to
      perceptions of nutritional value, and suggests that diet-related diseases may not
      be amenable to interventions based on education campaigns. Given recent
      initiatives towards trade liberalization and the creation of the World Trade
      Organization, tariffs or import bans may not serve as alternative measures to
      control consumption. This presents significant challenges to health policy-makers
      serving economically marginal populations and suggests that some population
      health concerns cannot be adequately addressed without awareness of the effects
      of global trade.

PMID- 11584735
TI  - Globalization and occupational health: a perspective from southern Africa.
AB  - Increased world trade has generally benefited industrialized or strong economies
      and marginalized those that are weak. This paper examines the impact of
      globalization on employment trends and occupational health, drawing on examples
      from southern Africa. While the share of world trade to the world's poorest
      countries has decreased, workers in these countries increasingly find themselves
      in insecure, poor-quality jobs, sometimes involving technologies which are
      obsolete or banned in industrialized countries. The occupational illness which
      results is generally less visible and not adequately recognized as a problem in
      low-income countries. Those outside the workplace can also be affected through,
      for example, work-related environmental pollution and poor living conditions. In
      order to reduce the adverse effects of global trade reforms on occupational
      health, stronger social protection measures must be built into production and
      trade activities, including improved recognition, prevention, and management of
      work-related ill-health. Furthermore, the success of production and trade systems
      should be judged on how well they satisfy both economic growth and population
      health.

PMID- 11584736
TI  - Global public goods and health: taking the agenda forward.
AB  - We examined recent special health initiatives to control HIV/AIDS, malaria, and
      tuberculosis, and make four policy recommendations for improving the
      sustainability of such initiatives. First, international cooperation on health
      should be seen as an issue of global public goods that concerns both poor and
      rich countries. Second, national health and other sector budgets should be tapped
      to ensure that global health concerns are fully and reliably funded;
      industrialized countries should lead the way. Third, a global research council
      should be established to foster more efficient health-related knowledge
      management. Fourth, managers for specific disease issues should be appointed, to
      facilitate policy partnerships. Policy changes in these areas have already begun
      and can provide a basis for further reform.

PMID- 11584737
TI  - Globalization and health: a framework for analysis and action.
AB  - Globalization is a key challenge to public health, especially in developing
      countries, but the linkages between globalization and health are complex.
      Although a growing amount of literature has appeared on the subject, it is
      piecemeal, and suffers from a lack of an agreed framework for assessing the
      direct and indirect health effects of different aspects of globalization. This
      paper presents a conceptual framework for the linkages between economic
      globalization and health, with the intention that it will serve as a basis for
      synthesizing existing relevant literature, identifying gaps in knowledge, and
      ultimately developing national and international policies more favourable to
      health. The framework encompasses both the indirect effects on health, operating
      through the national economy, household economies and health-related sectors such
      as water, sanitation and education, as well as more direct effects on population
      level and individual risk factors for health and on the health care system.
      Proposed also is a set of broad objectives for a programme of action to optimize
      the health effects of economic globalization. The paper concludes by identifying
      priorities for research corresponding with the five linkages identified as
      critical to the effects of globalization on health.

PMID- 11584739
TI  - Some health implications of globalization in Thailand.

PMID- 11584738
TI  - The Australian Measles Control Campaign, 1998.
AB  - The 1998 Australian Measles Control Campaign had as its aim improved immunization
      coverage among children aged 1-12 years and, in the longer term, prevention of
      measles epidemics. The campaign included mass school-based measles-mumps-rubella
      vaccination of children aged 5-12 years and a catch-up programme for preschool
      children. More than 1.33 million children aged 5-12 years were vaccinated at
      school: serological monitoring showed that 94% of such children were protected
      after the campaign, whereas only 84% had been protected previously. Among
      preschool children aged 1-3.5 years the corresponding levels of protection were
      89% and 82%. During the six months following the campaign there was a marked
      reduction in the number of measles cases among children in targeted age groups.

PMID- 11584740
TI  - Some health implications of globalization in the United Kingdom.

PMID- 11584741
TI  - Some health implications of globalization in Kerala, India.

PMID- 11584742
TI  - Drug studies in developing countries.

PMID- 11584743
TI  - Needed: tenable values or five to ten more earth-sized planets. Interview by
      Desmond Avery.

PMID- 11584744
TI  - Maternal mortality estimates are useful.

PMID- 11584745
TI  - Aircraft disinsection.

PMID- 11584746
TI  - Globalization--how healthy?

PMID- 11584747
TI  - TB drug prices slashed for poor countries.

PMID- 11584748
TI  - Electromagnetic fields in homes carry leukaemia risk for children, WHO agency
      says.

PMID- 11584749
TI  - [New tools for the study of animal trypanosomiasis in the Sudan: model-building
      of dangerous epidemiological passage by remote sensing geographic information
      systems].
AB  - Recent studies in a rangeland area of Burkina Faso showed that riparian tsetse
      flies (Glossina tachinoides and G. palpalis gambiensis) were found along the main
      rivers, but depending on their location, they had different hosts and were not
      infected by the same trypanosomoses. There were different epidemiological
      situations within a distance of a few kilometres, and local assessment of the
      trypanosome risk thus called for a global approach taking account of the
      environmental and human factors involved in the interfaces between hosts and
      vectors. Various types of information concerning entomology, parasitology,
      ecology, land occupation and animal production systems were fed into a
      Geographical Information System. High spatial resolution remote sensing tools and
      original modelling methods were used to detect the valley landscapes most
      favourable to tsetse flies, and describe land use by herds. The impact of
      trypanosomes appeared to depend largely on animal movements, watering practices
      and the degree of contact with riparian tsetse flies. Linking these types of
      information revealed the most dangerous sites in epidemiological terms, which in
      this case represented some 18% of the network initially surveyed.

PMID- 11584750
TI  - Coexistence of five Cercopithifilaria species in the Japanese rupicaprine bovid,
      Capricornis crispus.
AB  - The Japanese serow, Capricornis crispus (Bovidae, Caprinae, Rupicaprini), is
      parasitized by five Cercopithifilaria species: C. shohoi, recently described, and
      reexamined in this paper, C. multicauda n. sp., C. minuta n. sp., C.
      tumidicervicata n. sp., and C. bulboidea n. sp. Coinfections are frequent. The
      location (skin or subcutaneous regions) in the host of adult worms differed
      between the species, as did many morphological characters of both adults and
      microfilariae. The location (limbs, trunk, etc.) in the host of adult worms and
      dermal microfilariae seemed to differ depending on the species. Male and female
      worms of the same species had similar head shapes, buccal capsules, and, in four
      species, swellings in the anterior region of the body (because of the presence of
      a giant ventral pseudocoelomocyte). The Cercopithifilaria spp. from C. crispus
      were related to the primitive forms of the genus, parasites of Bovidae and
      Cervidae, presently recorded in Africa and Europe. C. bulboidea was particularly
      close to the most primitive species, C. ruandae and C. dermicola, in Africa, with
      the pairs of caudal papillae numbered 8 and 9 being distant from each other, but
      the species also had several specialized characters. Like C. rugosicauda in a
      European cervid, the four other species had pairs 8 and 9 close to each other;
      they reflect an evolutionary trend (hypertrophy of pair 6, and reduction and
      posterior migration of pair 7) that suggests diversification in the host.

PMID- 11584751
TI  - Onchocerca dewittei japonica n. subsp., a common parasite from wild boar in
      Kyushu Island, Japan.
AB  - We describe Onchocerca dewittei japonica n. subsp. from the Japanese wild boar,
      Sus scrofa leucomystax, in Oita, Kyushu Island, where all seven animals examined
      were found to be infected. This study began with efforts to identify the
      causative species in a recent case of zoonotic onchocerciasis. Compared with
      Onchocerca dewittei dewittei from Sus scrofa jubatus in Malaysia, which was
      reexamined here, our new subspecies has much greater space between the ridges on
      the females. In addition, its microfilariae (from uteri) are shorter (192-210
      microns compared with 228-247 microns), and only the posterior third of the
      microfilarial body is coiled, instead of the entire body. The Onchocerca species
      parasitic in suids (these two subspecies and O. ramachandrini from the warthog in
      the Ethiopian region) form a group sharing several characters. Among the most
      unusual characters are the body swellings (a specialized apparatus for mating,
      known in only a few other genera). In addition, longitudinal cuticular crests
      were found on males of both subspecies from wild boar and on females of O.
      ramachandrini.

PMID- 11584752
TI  - New Pudicinae (Trichostrongylina, Heligmosomoidea) coparasites of Proechimys
      longicaudatus (Caviomorpha) from Bolivia. I--Description of Pudica ginsburgi n.
      sp. and Heligmostrongylus chiarae n. sp.
AB  - Two new Pudicinae (Trichostrongylina, Heligmosomoidea, Heligmonellidae)
      coparasites of Proechimys longicaudatus (Caviomorph rodent) from Bolivia are
      described: Pudica ginsburgi n. sp. is differentiated from all the other species
      of the genus by the great length of the spicules and of the vestibule and by a
      different ratio of the length of the spicules on the length of the body.
      Heligmostrongylus chiarae n. sp. has very developed rays 4, strongly divergent
      from rays 5 as occurs in three other species, H. almeidai (Durette-Desset &
      Tcheprakoff, 1969), a parasite of Trichomys apereoides (= Cercomys cunicularius)
      from Brazil, H. squamastrongylus (Travassos, 1937), a parasite of Proechimys oris
      from Brazil and H. proechimysi Durette-Desset, 1970, a parasite of Proechimys
      semispinosus from Columbia. The specimens from Bolivia are differentiated from
      the three species by the division of the dorsal ray (anterior half versus
      posterior half) and by a different ratio of the length of the spicules on the
      length of the body.

PMID- 11584753
TI  - Sex discriminatory effect of the acanthocephalan Acanthocephaloides propinquus on
      a gobiid fish Gobius bucchichii.
AB  - Most studies which aim at detecting effects of parasites on fish show that
      intermediate stages of parasites affect their host while adult parasites are
      usually less virulent in the final host. We studied the effect of the
      acanthocephalan Acanthocephaloides propinquus on one of its final hosts, the fish
      Gobius bucchichii. This study showed that the adult parasites affect host
      fitness. Moreover, our results showed that at the same level of infection in male
      and female gobiids, the female's reproductive success was negatively correlated
      to parasite abundance while the male's reproductive success was not. The negative
      effects on females includes reductions in gonado-somatic index and egg
      production. We hypothesized that it might be more difficult for females to
      compensate the cost of parasitism because of the very high cost of egg
      production. We discussed these results in terms of host population regulation.

PMID- 11584754
TI  - Genetic variability among cercariae of the Schistosomatidae (Trematoda: Digenea)
      causing swimmer's itch in Europe.
AB  - Ribosomal DNA sequences of the internal transcribed spacer 1 (ITS1) were obtained
      from schistosome cercariae responsible for swimmer's itch in Europe. Two types of
      ITS1 (1100 and 1400), which differ by the number of repeated patterns were found
      among cercariae shedded by Lymnaea ovata and L. auricularia (Lymnaeidae). A
      phylogenetic analysis of the ITS1 region showed that sequences of each type form
      two well-defined clades. An adult of Trichobilharzia regenti isolated from the
      nasal vessels of Anas platyrhynchos (Anatidae) was found to correspond to the
      cercaria type 1400. The sequencing of several ITS1 clones from a single cercaria
      of each type, as well as a specific PCR-based test suggested that both ITS1 types
      do not co-occur within a single individual.

PMID- 11584755
TI  - Gametocytaemia in Senegalese children with uncomplicated falciparum malaria
      treated with chloroquine, amodiaquine or sulfadoxine + pyrimethamine.
AB  - Plasmodium falciparum gametocytaemia was studied in 266 Senegalese children
      (median 4 years, range 0.5-16) with uncomplicated malaria treated with
      chloroquine (CQ), amodiaquine (AQ) or sulfadoxine + pyrimethamine (SP). The
      proportion of resistant infections in vivo to these drugs was 44%, 16% and 7%,
      respectively. Gametocytes were counted by microscopy in thick smears on days 0,
      4, 7 and 14 after treatment. There was a peak of gametocytaemia one week after
      treatment; on days 0, 7 and 14 the gametocyte prevalences were 35%, 73% and 63%,
      and the geometric means of gametocyte densities were 1.3, 12.5 and 5.6/microliter
      of blood. Three factors were found to influence gametocytaemia: treatment,
      efficacy of treatment, and duration of symptoms before treatment. Gametocyte
      prevalence and density significantly appeared higher in children treated with SP
      than with CQ, and higher with CQ than with AQ. Gametocyte prevalence and density
      were higher in resistant than in sensitive infections. The period between the
      appearance of the first clinical symptoms and treatment was positively and
      significantly linked to gametocyte prevalence and density on days 0 and 4. Early
      treatment with AQ, against sensitive infection, was followed by the lowest
      gametocytaemia. By contrast, treatment with SP against resistant infection was
      followed by the highest gametocytaemia. No clear relationship was observed
      between the density of asexual stages on day 0 and the gametocytaemia at any day
      between days 0 and 14. The epidemiological significance of post-therapeutic
      gametocytaemia and its possible role in the spread of resistant parasites are
      underlined. Solutions are proposed in order to avoid or reduce this
      gametocytaemia.

PMID- 11584756
TI  - Ultrastructural studies of Sarcocystis cruzi (Hasselmann, 1926) Wenyon, 1926
      infection in cattle (Bos taurus): Philippine cases.
AB  - This paper documents the first report of Sarcocysti s cruzi infection in
      domesticated cattle (Bos taurus) in the Philippines. Fusiform-shaped microscopic
      sarcocysts (183-578 microns long and 20-98 microns wide) with distinct septae
      were found in the skeletal, striated and heart muscle. The sarcocyst wall or
      parasitophorous vacuolar membrane, 1.37-2.75 microns thick consisted of closely
      packed villar protrusions 80-400 nm in dm. Middle and distal segments of VP were
      bent approximately 90 degrees parallel to the cyst wall surface. The villar core
      lacked microtubules, and at some points, the distal ends of the VP collectively
      formed conical tufts. Primary cyst wall had numerous 70-100 nm bubble-like
      undulations, and the ground substance was 0.25-0.5 micron in thickness. The
      ultrastructure of S. cruzi cyst wall typifies the Type 7 sarcocyst wall, and
      bears close similarities with the Philippine and the Vietnam strain of bubaline
      Sarcocystis levinei.

PMID- 11584757
TI  - A controlled prospective trial of the prophylactic effect of a single dose of
      ivermectin against Onchocerca volvulus.
AB  - A clinical trial was conducted in Cameroon in order to evaluate in humans the
      possible effect of a single dose of ivermectin (150 micrograms per kg) on the pre
      adult stages of Onchocerca volvulus. The incidence of the skin microfilariae was
      measured in two groups of patients who initially had negative biopsies, and who
      were subsequently treated, immediately after the seasonal peak of transmission of
      O. volvulus, either with a combination of ivermectin + ferrous sulphate, or with
      ferrous sulphate alone. One year after the treatment, i.e. 14 months after the
      start of the transmission period, the proportion of patients with positive skin
      biopsies, and their mean microfilarial loads, did not differ significantly
      between the two groups. Thus a single dose of ivermectin does not seem to have
      any perceptible prophylactic effect against O. volvulus.

PMID- 11584758
TI  - Human infection with Onchocerca dewittei japonica, a parasite from wild boar in
      Oita, Japan.

PMID- 11584759
TI  - [Osteoporosis: which prophylaxis and therapy?].

PMID- 11584760
TI  - [Caspofungin. A new antimycotic agents from the echinocandin group].

PMID- 11584761
TI  - [Therapy of chronic heart failure. Recommendations of the Medical Commission of
      the German Medical Society (continuing education credit)].

PMID- 11584762
TI  - [Rubella].

PMID- 11584763
TI  - [Cancer diets--significant or dangerous?].

PMID- 11584764
TI  - AIDS--the way forward.

PMID- 11584765
TI  - Scientific misconduct in cancer clinical trials.

PMID- 11584766
TI  - Laboratory monitoring of HIV--after access to antiretroviral drugs, the next
      challenge for the developing world.

PMID- 11584767
TI  - Hyperbaric oxygen therapy for children with cerebral palsy.

PMID- 11584768
TI  - The patient-physician relationship.

PMID- 11584769
TI  - The Aversion Project--sex change operations in the SADF.

PMID- 11584770
TI  - First AIDS vaccine trials next year.

PMID- 11584771
TI  - Ongoing human rights abuses.

PMID- 11584772
TI  - World's doctors against torture.

PMID- 11584773
TI  - Topical photodynamic therapy in dermatology.
AB  - ALA-PDT is an effective therapy for non-hyperkeratotic facial actinic keratoses,
      Bowen's disease and superficial basal cell carcinoma. Additional applications
      remain at the experimental stage, with early potential suggested in acne and
      refractory warts. PDT offers the advantages of being non-invasive, well tolerated
      in slow healing sites, and tissue sparing, leaving the skin surrounding the
      tumour intact and functional. ALA-PDT may be particularly useful for large
      superficial tumours and for lesions in anatomical sites where disfigurement from
      conventional therapies may be a particular risk. The development of powerful
      filtered non-laser sources, along with the topical application of
      photosensitizer, makes ALA-PDT a more easily accessible therapy.

PMID- 11584774
TI  - Health databases: basic legal and ethical principles.

PMID- 11584775
TI  - How the Council for Medical Schemes is regulating the new health care economy.

PMID- 11584776
TI  - A short prescription for practice revival.

PMID- 11584777
TI  - Does antiretroviral therapy have a role to play in the control of tuberculosis in
      South Africa?

PMID- 11584778
TI  - Treatment of acute asthma--a metered dose inhaler with spacer is an optimal
      delivery system.

PMID- 11584779
TI  - To test or not to test--ethical dilemmas and practical realities in the use of co
      trimoxazole and nevirapine in HIV-infected adults.

PMID- 11584780
TI  - Computed tomography features of basal ganglia and periventricular calcifications
      in childhood.

PMID- 11584781
TI  - Metered dose inhalers and spacers for childhood asthma--will increasing
      availability improve asthma care?

PMID- 11584782
TI  - Increase in childhood asthma admissions in an urbanising population.
AB  - OBJECTIVE: In South Africa, rapid urbanisation has increased the risk of
      childhood asthma. This report reviews the pattern of asthma admissions to the
      Paediatric Department of Ga-Rankuwa Hospital, South Africa, from 1986 to 1996.
      DESIGN: Inpatient admission data were reviewed for 1986-1996. A detailed analysis
      of the records of asthma patients admitted between 1992 and 1996 was done.
      Outpatient data were reviewed from 1992. SETTING: Ga-Rankuwa Hospital, situated
      on the border of the Gauteng and North West provinces of South Africa and serving
      a large black population in various stages of urbanisation. MAIN OUTCOME
      MEASURES: Trends in admission numbers and demographic characteristics. RESULTS:
      Asthma admissions were 2.5 times higher in 1996 than 1986. The greatest increase
      in admissions was in the 1-47-month age group. The male to female ratio was
      1.5:1. More patients came from urban than from rural areas. Admissions peaked
      during the summer. Re-admissions occurred most frequently within 3 months of the
      first admission. CONCLUSION: Paediatric asthma admissions have shown an increase
      in the past decade. This may be associated with changes in the environment of the
      community. There is a need for preventive programmes for asthma at community and
      national level.

PMID- 11584783
TI  - Acceptability of the female condom in different groups of women in South Africa-
      a multicentred study to inform the national female condom introductory strategy.
AB  - OBJECTIVES: To assess the acceptability of the female condom to different groups
      of women and their partners in South Africa. DESIGN: Descriptive, cross-sectional
      study. SETTING: Multicentre study conducted in five sites. SUBJECTS: The study
      recruited 678 women from five centres to an acceptability trial of the female
      condom. Acceptability and successful use varied between the centres. OUTCOME
      MEASURES: Factors affecting successful use and willingness and intention to use
      the method again. RESULTS: In total, 209 women used the condom at least once.
      Discontinuation rates were high, with partner reluctance to try the method as the
      main reason given for discontinuation at all sites. Women who had previous
      experience with the male condom or who received a more intensive training session
      generally found the device easier to use. The main issues concerning women were
      over-lubrication (27%) and concern that the device was too large (28%). The
      majority of women said that they would be interested in using the method again
      (86%) and would recommend it to friends (95%). CONCLUSIONS: Overcoming partner
      opposition is an important issue to address when introducing the method. The
      study was used to address the national introductory strategy of the female
      condom, which began in 1998.

PMID- 11584784
TI  - Early diagnosis of prostate cancer in the Western Cape.
AB  - BACKGROUND: Early stage prostate cancer does not cause symptoms, and even
      metastatic disease may exist for years without causing symptoms or signs. Whereas
      early stage prostate cancer can be cured with radical prostatectomy or
      radiotherapy, the prognosis of patients with locally advanced or metastatic
      cancer is significantly poorer. OBJECTIVES: In view of the high incidence of
      advanced and therefore incurable prostate cancer seen at the oncology clinic of
      the Department of Urology, Tygerberg Hospital, we started a prostate clinic with
      the aim of detecting early stage prostate cancer which is potentially curable. A
      secondary objective was to investigate the question whether there is a higher
      incidence of prostate cancer among black African men. PATIENTS AND METHODS: Men
      aged 50-70 years were invited by means of media communications (newspaper and
      radio) to attend our prostate clinic for a free physical examination, including a
      digital rectal examination (DRE) and serum prostate specific antigen (PSA) assay.
      If the DRE was clinically suspicious of malignancy and/or the serum PSA was > 4
      ng/ml, the patient was appropriately counselled and referred for transrectal
      ultrasound (TRUS)-guided sextant prostate biopsy. RESULTS: In the period June
      1997-September 1999 a total of 1,056 men attended the prostate clinic. Biopsies
      were indicated in 160 cases, and were obtained in 114 (71.3%, i.e. 10.8% of the
      entire cohort). Prostate cancer was detected on first biopsy in 3.5% of the
      entire group of men (in 35.9% of those with a clinically abnormal DRE, in 41.3%
      of those with a serum PSA > 4 ng/ml and in 88.6% of those with an abnormal DRE
      and serum PSA > 4 ng/ml. In the 37 men with prostate cancer, the clinical tumour
      stage was T1-2 in 83.8% and T3-4 in 16.2%. In the group of patients with clinical
      stage T1-2 tumours, the treatment was watchful waiting in 62.5% of cases,
      radiotherapy in 20.8% and radical prostatectomy in 16.7%. Analysis of the data
      according to race showed that in the group of 47 black men there was a higher
      percentage of clinically abnormal DRE, PSA > 4.0 ng/ml and biopsies showing
      malignancy, and a higher overall prostate cancer detection rate (8.5%).
      CONCLUSIONS: Our prostate cancer detection rate of 3.5% is slightly lower than
      that reported in larger studies (4.7%), which may be due to the fact that
      prostate biopsy was performed in only 71% of those who had an indication for
      biopsy. In the men diagnosed with clinically localised prostate cancer,
      potentially curative treatment was given in only 37.5% of cases. This compares
      unfavourably with the historical cohort of men seen at our oncology clinic, where
      53% received potentially curative treatment, and a large European study where
      potentially curative treatment was given in 89% of cases. Our finding that black
      men had a higher percentage of clinically abnormal DRE, PSA > 4.0 ng/ml and
      biopsies showing malignancy and a higher overall detection rate of prostate
      cancer should be interpreted with caution, since black men comprised only 4.5% of
      our overall study cohort.

PMID- 11584785
TI  - Serum prostate-specific antigen as surrogate for the histological diagnosis of
      prostate cancer.
AB  - INTRODUCTION: To determine whether there is a cut-off value of serum prostate
      specific antigen (PSA) which can be used confidently to make the diagnosis of
      prostate cancer, thereby obviating the need for biopsy. PATIENTS AND METHODS:
      During the period October 1991 to March 1998 the Department of Chemical Pathology
      at Tygerberg Hospital performed a total of 6,733 serum PSA assays on 3,960
      patients. The histopathological and clinical diagnoses of these patients were
      obtained from records in the departments of Anatomical Pathology, Urological
      Oncology and Radiation Oncology. The serum PSA levels were correlated with the
      histopathology reports, using different PSA cut-off values ranging from 5 to 500
      ng/ml, to calculate the sensitivity, specificity, and positive and negative
      predictive values of each cut-off value of PSA in predicting the presence of
      prostate cancer. RESULTS: In total, 3,837 (57%) of the 6,733 serum PSA assays
      were < or = 4 ng/ml, 1,045 (15.5%) of the assays were > or = 50 ng/ml, and 798
      (11.9%) were > or = 100 ng/ml. Of the total of 3,960 individual patients, 531
      (13.4%) had a serum PSA > or = 50 ng/ml and 423 (10.7%) had a PSA > or = 100
      ng/ml. A serum PSA of > or = 30 ng/ml had a positive predictive value (PPV) of
      90% at a specificity of 87% and sensitivity of 78%, while a PSA > or = 60 ng/ml
      had a PPV of 98% at a specificity of 98% and sensitivity of 65% for the presence
      of prostate cancer. The PPV reached 99% at a PSA > or = 100 ng/ml and 100% at a
      PSA > or = 500 ng/ml, with a specificity of 99% and 100%, but sensitivity of only
      53% and 19%, respectively. CONCLUSIONS: A serum PSA > or = 60 ng/ml has a PPV of
      98% for the presence of adenocarcinoma of the prostate, and may be used as a
      surrogate for histological diagnosis where facilities for obtaining prostatic
      biopsies are not readily available, thus decreasing costs and patient morbidity.

PMID- 11584786
TI  - Colorectal carcinoma--a new threat to black patients? A retrospective analysis of
      colorectal carcinoma received by the Institute for Pathology, University of
      Pretoria.
AB  - OBJECTIVE: To compare black and white patients with colorectal carcinoma treated
      at Pretoria Academic and Kalafong hospitals, and to compare pathological trends
      of our study population with others reported in the literature. DESIGN: A
      retrospective study of all cases of resected colorectal carcinomas received by
      our department during the periods 1986-1987 (82 cases) and 1996-1997 (91 cases).
      To investigate variables of age, race and gender distribution in the two study
      populations. METHODS: Routinely stained histological sections of all relevant
      cases were examined. Findings regarding age, gender, population group, anatomical
      location of the tumour and presence of other pathological lesions were recorded.
      Changes in the referral population and number of surgical specimens received were
      also considered during statistical analysis of the study findings. RESULTS: There
      has been a significant increase in the number of black patients with colorectal
      carcinoma at our Institute. In addition, adenomatous polyps were found in 9 of
      our black patients (1996/97). This is significantly higher than expected from
      reports in the literature. This could be predictive of an increase in incidence
      of colorectal carcinomas in our black population. Black patients were also found
      to be considerably younger at age of presentation than their white counterparts.
      A further significant finding was a considerable increase in the number of black
      females under the age of 40 years from 1986/87 to 1996/97. On the other hand, the
      number of white females above 40 years of age decreased considerably over this
      time. The reason for this finding is uncertain and warrants further study.

PMID- 11584787
TI  - Dose-area product measurements during barium enema radiograph examinations--a
      Western Cape study.
AB  - The aim of this study was to obtain a direct measurement of the typical dose
      delivered to an average adult patient during a barium enema examination.
      Measurement was done on a a sample of 50 patients at three departments, using a
      dose-area product (DAP) meter. The comparison of the results with UK median
      levels indicates that the doses measured in South Africa are higher (41 Gy cm2
      (dose x area) v. 48 Gy cm2). Patient protection can be improved by comparing
      local practice with national reference levels. The values obtained in this study
      (first quartile 35 Gy cm2, median 48 Gy cm2, third quartile 84 Gy cm2) are
      recommended as initial reference dose levels for barium enemas in South Africa.

PMID- 11584788
TI  - Children of divorce in the 1990s: an update of the Amato and Keith (1991) meta
      analysis.
AB  - The present study updates the P. R. Amato and B. Keith (1991) meta-analysis of
      children and divorce with a new analysis of 67 studies published in the 1990s.
      Compared with children with continuously married parents, children with divorced
      parents continued to score significantly lower on measures of academic
      achievement, conduct, psychological adjustment, self-concept, and social
      relations. After controlling for study characteristics, curvilinear trends with
      respect to decade of publication were present for academic achievement,
      psychological well-being, self-concept, and social relations. For these outcomes,
      the gap between children with divorced and married parents decreased during the
      1980s and increased again during the 1990s.

PMID- 11584789
TI  - Attachment insecurity and the distinction between unhappy spouses who do and do
      not divorce.
AB  - The hypothesis that attachment insecurity would be associated with remaining in
      an unhappy marriage was tested. One hundred seventy-two newly married couples
      participated in a 4-year longitudinal study with multiple assessment points.
      Hierarchical linear models revealed that compared with spouses in happy marriages
      and divorced spouses, spouses who were in stable but unhappy marriages showed the
      highest levels of insecurity initially and over time. Spouses in stable, unhappy
      marriages also had lower levels of marital satisfaction than divorced spouses and
      showed relatively high levels of depressive symptoms initially and over time.
      Results suggest that spouses at risk for stable, unhappy marriages can be
      identified early and may benefit from interventions that increase the security of
      spouses' attachment to each other.

PMID- 11584790
TI  - Maritally violent men's heart rate reactivity to marital interactions: a failure
      to replicate the Gottman et al. (1995) typology.
AB  - In an attempt to replicate the J. M. Gottman et al. (1995) batterer typology, 58
      men who had engaged in moderate-to-severe marital violence in the past year were
      studied. The sample was split into Gottman et al.'s Type 1 men (i.e., whose heart
      rates decreased, from baseline, during a marital conflict task) and Type 2 men
      (i.e., whose heart rates increased). The groups did not differ in the manner
      predicted on measures of marital violence, antisocial or aggressive-sadistic
      personality, drug dependence, criminality, general violence, childhood exposure
      to interparental violence, behavior during marital interactions, or relationship
      stability. Contrary to expectations, wives of Type 1 men rated their husband as
      more jealous and angry and reported more marital distress. In the only finding
      consistent with Gottman et al., Type 2 men scored higher on a measure of
      dependent personality. Implications for future research are discussed.

PMID- 11584791
TI  - Crime, hostility, wife battering, and the heart: on the Meehan et al. (2001)
      failure to replicate the Gottman et al. (1995) typology.
AB  - Comments on the J. C. Meehan, A. Holtzworth-Munroe, and K. Herron (2001) failure
      to replicate the J. M. Gottman et al. (1995) results of 2 different types of
      batterers, defined by heart rate reactivity: Type 1 men lowered their heart rate
      from baseline to the high-conflict marital discussion, and Type 2 men increased
      their heart rate from baseline to the high-conflict marital discussion.
      Discussion is about criminality-psychopathy literature associated hypoarousal and
      hyporeactivity and the hostility-cardiovascular disease literature, which reports
      associated hyperreactivity and hostility related to cardiovascular disease. The
      Type 1-Type 2 distinction should be referred to these two venerable literatures.
      This article proposes the hypothesis that the Meehan et al. study failed to
      replicate Gottman et al. because it used a low-conflict marital discussion rather
      than the high-conflict discussion Gottman et al. used. This article reviews a
      study that did use a high-conflict marital task and found results generally
      supporting the Gottman et al. findings.

PMID- 11584792
TI  - Heart rate reactivity in male batterers: reply to Gottman (2001) and a second
      look at the evidence.
AB  - Together, the results of 3 studies examining heart rate reactivity (HRR) in male
      batterers do not provide strong support for the J. M. Gottman et al. (1995)
      batterer typology. All research groups found similar proportions of severely
      violent male batterers who show heart rate increases or decreases during a
      marital conflict discussion, but there was inconsistent validation of this
      taxonomy on variables of interest. This difference was also found among less
      violent and nonviolent men. The authors believe HRR may be useful for
      differentiating batterers on the dimension of anger-hostility but are less
      optimistic that HRR will reliably identify psychopathic or antisocial batterers.
      The authors do not agree that low levels of marital interaction conflict led to
      their failure to replicate. Reanalysis of data from J. C. Meehan, A. Holtzworth
      Munroe, and K. Herron (2001) suggests baseline artifacts may be an important
      determinant of HRR differences. Methodological changes may improve the
      reliability of HRR assessment.

PMID- 11584793
TI  - Physical aggression in a community sample of at-risk young couples: gender
      comparisons for high frequency, injury, and fear.
AB  - The associations of frequent physical aggression, injury, and fear were examined
      for a community-based sample of at-risk young couples who were dating,
      cohabiting, or married. It was hypothesized that frequent physical aggression
      toward a partner, in the range of shelter samples, is largely caused by
      antisocial behavior and mutual couple conflict and, thus, that there would be
      greater similarity across genders in such behavior than has previously been
      supposed. It was also predicted that levels of injury and fear would be higher in
      women but that some men would experience these impacts. Findings indicated
      similarity across genders both in the prevalence of frequent aggression and in
      its association with antisocial behavior. Furthermore, such aggression was likely
      to be bidirectional in couples. Contrary to the hypothesis of the study, rates of
      injury and fear for the women were not significantly higher than for the men.

PMID- 11584794
TI  - Maternal disclosure of mothers' HIV serostatus to their young children.
AB  - Mothers' disclosure of their HIV serostatus to their noninfected young children
      and factors associated with disclosure were investigated among 135 families.
      Overall, 30% of the mothers had personally disclosed their serostatus to their
      children. Mothers who disclosed reported higher levels of social support in their
      lives than mothers who did not disclose. Children whose mothers had disclosed to
      them displayed lower levels of aggressiveness and negative self-esteem compared
      to children whose mother had not disclosed. These findings indicate that for this
      sample, no negative effects were observed among young children to whom mothers
      have personally disclosed their HIV serostatus.

PMID- 11584795
TI  - Observed maternal strategies and children's health locus of control in low-income
      Mexican American families.
AB  - This study examined the relationship among mothers' health locus of control
      (HLOC) beliefs, their socialization strategies, and their children's HLOC beliefs
      in 80 low-income Mexican American families. Maternal socialization strategies
      were assessed from videotaped interactions of mothers and children engaged in a
      structured task. Factor analysis of the coded strategies yielded 4 factors: Tell
      Answer, Teaching, Clarify, and Reinforce. Findings indicated that maternal-health
      internally scores negatively predicted mothers' use of the Tell Answer strategies
      and positively predicted their use of Teaching strategies. Mothers who believed
      that Powerful Others (e.g., health professionals) controlled their health were
      more likely to use the Tell Answer strategy. In contrast, mothers who believed
      that health was due to chance were less likely to use Teaching. Maternal use of
      Teaching strategies predicted children's internal HLOC, whereas maternal Tell
      Answer strategies predicted children's external HLOC. Findings suggest that
      mothers' HLOC beliefs influence the socialization strategies they use and that
      these strategies are associated with children's HLOC beliefs.

PMID- 11584796
TI  - Interpersonal predictors of dieting practices among married couples.
AB  - The relations between couples' marital quality and dieting behavior were
      examined. One-hundred eighty-seven married couples' dieting behaviors, marital
      quality, body mass index, weight concerns, depression, and self-esteem were
      assessed. Results indicate that the relation between healthy dieting behaviors
      and marital quality is similar for both husbands and wives. However, among wives,
      marital discord predicted unhealthy dieting behaviors, even after wives' body
      mass index, weight concerns, self-esteem, and depression were controlled for.
      Furthermore, wives' self-esteem interacted with marital quality when predicting
      unhealthy dieting. These findings suggest gender differences in the relations
      between marital quality and dieting behaviors and are consistent with previous
      research suggesting that men and women have differential response patterns to
      marital disharmony, with women tending to internalize negative affect experienced
      in their marriage.

PMID- 11584797
TI  - Maternity leave, women's employment, and marital incompatibility.
AB  - This research investigated the relationship between the length of women's
      maternity leave and marital incompatibility, in the context of other variables
      including the woman's employment, her dissatisfaction with the division of
      household labor, and her sense of role overload. Length of leave, work hours, and
      family salience were associated with several forms of dissatisfaction, which in
      turn predicted role overload. Role overload predicted increased marital
      incompatibility for experienced mothers but did not for first-time mothers, for
      whom discrepancies between preferred and actual child care were more important.
      Length of maternity leave showed significant interactions with other variables,
      supporting the hypothesis that a short leave is a risk factor that, when combined
      with another risk factor, contributes to personal and marital distress.

PMID- 11584798
TI  - Cultural perspective on work and family: dual-earner Israeli-Jewish and Arab
      families at the transition to parenthood.
AB  - Parents' functioning in the work and family roles was examined in traditional and
      modern societies at the transition to parenthood. Participants were 162 dual
      earner Israeli-Jewish and Arab families, who were interviewed and observed in
      dyadic and triadic interactions. Arab parents reported better adaptation to work
      following the first childbirth, and the triadic family process in Jewish families
      was more cohesive. Child care arrangements, part-time employment, easier infant
      temperament, and lower separation anxiety predicted maternal readaptation to
      work. Traditional sex-role attitudes, career centrality, full-time employment,
      and marital satisfaction predicted fathers' work adaptation. Parents' family
      focus, marital satisfaction, and responsive parenting correlated with a cohesive
      triadic process. Discussion considered the impact of nuclear- and extended-family
      living arrangements on the emerging work and family roles in young couples.

PMID- 11584799
TI  - Parent x child socialization: implications for the development of depressive
      symptoms.
AB  - A Parent x Child model of socialization was applied to the development of
      depressive symptoms. It was expected that when parents used intrusive support
      frequently, children engaging in negative self-evaluative processes would be more
      vulnerable to depressive symptoms than children engaging in positive self
      evaluative processes. Children in the 5th through 7th grades took part in a 2
      wave longitudinal study over 6 months. Parents' use of intrusive support was
      assessed using reports from children (N = 806) and mothers (N = 74). Children's
      self-evaluative processes and depressive symptoms were assessed using reports
      from children. The results suggest that both parents and children contribute to
      the development of depressive symptoms. When parental intrusive support was high,
      children engaging in negative self-evaluative processes experienced more
      depressive symptoms over time than did children engaging in positive self
      evaluative processes.

PMID- 11584800
TI  - Coparenting, family process, and family structure: implications for preschoolers'
      externalizing behavior problems.
AB  - This study examined how aspects of triadic-level family interaction relate to
      preschoolers' externalizing behavior problems. The quality of coparenting, family
      affective processes, and family structure was assessed at 3 years, and mothers,
      fathers, and teachers reported on children's externalizing behavior problems at 4
      years. High levels of supportive coparenting and more adaptive family structures
      were associated with fewer externalizing behavior problems, whereas high levels
      of undermining coparenting and negative affect and less adaptive family
      structures were associated with more externalizing behavior problems. Moreover,
      the quality of family affectivity and family structure interacted with
      coparenting and appeared to influence its effects on the family. This study
      highlights the importance of focusing on triadic, family-level variables for
      understanding children's behavior problems.

PMID- 11584801
TI  - Initial assessment and management of pediatric trauma patient.
AB  - The initial evaluation and treatment of the pediatric trauma patient require an
      organized, thorough approach. All patients must be assumed to have multiple
      injuries until proven otherwise. Resuscitation efforts should be aggressive to
      avoid the onset of irreversible shock. The ability to recognize and effectively
      treat shock are all that are required in the vast majority of injured patents in
      order to gain stability. The adequate assessment and treatment of the ABCs will
      provide adequate treatment of the patient's other injuries, leading to an overall
      improvement in morbidity and mortality. Thus, the ABCs play an essential role in
      the initial evaluation and treatment of the pediatric trauma patient.

PMID- 11584802
TI  - The surgical airway.
AB  - Traumatic airway injuries are rare in children, partly due to their unique
      anatomy. The larynx is well protected from direct blows behind the mandibular
      arch, and only a small portion of the trachea is unprotected above the manubrium
      due to the relatively short neck. Furthermore, the tracheobronchial tree is less
      prone to injuries as compared with adults due to its elasticity. A high index of
      suspicion is thus needed to adequately diagnose and manage pediatric airway
      injuries. Laryngotracheal injuries in particular may present with discreet
      initial symptoms that if undiagnosed may rapidly progress to loss of airway. The
      most important signs of laryngeal injury include hoarseness and subcutaneous
      emphysema. Tracheobronchial injuries often present with dramatic symptoms, the
      most common being pneumothorax, which does not resolve after placement of chest
      tube, or large persistent air leaks. Endoscopy is mandatory on suspicion of
      injury to the larynx, trachea, or bronchi. CT scan may be helpful in determining
      the extent of injury to the larynx. Correct management of the airway in
      laryngotracheal injuries has a direct impact on morbidity and mortality.
      Endotracheal intubation over a flexible bronchoscope during spontaneous
      ventilation and in halothane anesthesia is the method of choice in children, but
      it should be performed in the operating room with the possibility of emergency
      tracheotomy. Cricothyroidotomy should be avoided in all laryngotracheal injuries
      because this method may aggravate the injury. Most laryngotracheal injuries in
      children can be conservatively managed. Extensive injuries, including displaced
      fractures of the cartilage, injuries to the recurrent nerves, and laryngotracheal
      separation, require surgical intervention. Injuries to bronchi and the thoracic
      trachea that do not cause a persistent air leak, and where the lungs expand
      completely after insertion of chest tubes, may be managed conservatively. All
      other injuries to the tracheobronchial tree should be repaired surgically as soon
      as feasible. Induction of anesthesia and opening of the chest may make
      ventilation difficult and are best managed by selective intubation of the
      contralateral lung. Long-term outcome after laryngeal, tracheal, and bronchial
      injuries in children, if managed swiftly and accurately, is usually excellent
      unless other injuries are present. The final result is improved by early
      recognition and early surgical intervention. These children need to be followed
      endoscopically for months and sometimes years in order to diagnose and treat
      stenoses as soon as they occur. Long-term pulmonary function has been shown to be
      excellent. Children with bilateral recurrent nerve paralysis may not fully
      recover voice or airway.

PMID- 11584803
TI  - Thoracic injuries in children.
AB  - The successful management of pediatric thoracic injuries includes immediate and
      careful evaluation of the injury type and severity. Early treatment can be
      conservative in nature or require surgical management. Prompt intervention can
      reduce morbidity and mortality rates, associated complications, and ensure
      optimal outcomes.

PMID- 11584804
TI  - Respiratory support of the head-injured child.
AB  - Meticulous care of the head-injured child revolves around the prevention of
      secondary injury. In no arena is this more crucial than in the respiratory
      support of the pediatric traumatic brain-injured patient. Careful attention to
      intubation techniques, maintenance of adequate oxygen delivery, avoidance of
      hypoxia, and judicious use of PEEP and other respiratory therapeutics all can be
      invaluable in the care of the pediatric traumatic brain-injured patient and may
      ultimately enhance outcome in this sometimes devastating disease.

PMID- 11584805
TI  - Pulmonary and respiratory complications of pediatric trauma.
AB  - Pediatric trauma management requires both operative and nonoperative (supportive)
      care. Fewer than 15% of pediatric trauma patients require surgery (Children's
      Hospital of Michigan Registry Data, excluding fractures), and the primacy of
      closed head injury and the multisystem nature of pediatric trauma dictate
      assessment and therapy. Complications arise at every level, including fluid
      resuscitation (too much or too little), antibiotics (too late), or pain control
      (inadequate). The institution of mechanical ventilation that is usually life
      saving carries its own risks including those associated with intubation
      (perforation, aspiration, pro longed endotracheal intubation (stricture,
      pneumonia), and barotrauma (ventilator-induced lung injury). Minor procedures,
      such as thoracentesis, chest tube insertion, and pericardiocentesis, can all be
      complicated by perforation and hemorrhage. Major interventions, including
      laparotomy and thoracotomy, can result in hemorrhage, air leak, abdominal
      compartment syndrome, phrenic nerve and thoracic duct injury, postoperative
      abscess, and septicemia. Transfusion, cardiopulmonary bypass, and invasive
      monitoring can result in coagulopathy and vascular injury. Prolonged
      resuscitation and operative explorations can cause hypothermia and coagulopathy
      and initiate a cascade of multiorgan failure and ARDS. There is no doubt that
      rapid evacuation, prompt resuscitation, and organized systems of pediatric trauma
      care have reduced the overall mortality of childhood trauma. The higher velocity
      of travel and an increasingly chaotic urban environment have resulted in more
      multitrauma cases and in injuries of higher severity requiring more sophisticated
      and complicated diagnostic and therapeutic modalities. Our ability to identify
      life-threatening injuries, to provide expedited and definitive care, and to
      reduce and detect the complications predicted by these injuries and their
      treatment will result in long-term improvements in survival and significant
      reductions in morbidity.

PMID- 11584806
TI  - Nutritional support of the pediatric trauma patient: a practical approach.
AB  - It is mandatory to evaluate and develop a plan for nutritional support for all
      injured children who are hospitalized. Although most childre" will rapidly resume
      normal oral intake, more severely injured children should be started on
      parenteral or enteral nutrition as soon as possible after admission. The mode of
      delivery and composition of nutritional support differ depending on the clinical
      setting and can change during the recovery period. Development of an initial plan
      and modification of the plan depending on the child's response will most
      effectively meet the metabolic demands after injury.

PMID- 11584807
TI  - Paralyzation and sedation of the ventilated trauma patient.
AB  - Sedation and analgesia will be required in the mechanically ventilated pediatric
      trauma patient. Adequate provision of both has a number of beneficial physiologic
      and psychologic effects. There are a number of categories of sedatives available
      for use. To provide optimal management and avoid adverse sequellae, an
      understanding of the pharmacology of these agents should guide their use in this
      group of patients, who are likely to have variable pharmacokinetic responses and
      therapeutic goals. Neuromuscular blockade is warranted in only a select
      population of mechanically ventilated ICU patients. Given newer ventilator
      technology and modes, it is certainly possible to achieve patient-ventilator
      synchrony with the use of sedation alone. Neuromuscular blockade is associated
      with a number of possible adverse effects, including prolonged weakness or
      paresis, and prohibits ongoing clinical assessment. When the use of this therapy
      is deemed necessary, it is again essential to understand the pharmacodynamics and
      pharmacokinetics of the available agents to avoid potential complications.

PMID- 11584808
TI  - [Pathophysiological features and treatment of rhinitis in aged patients].

PMID- 11584809
TI  - Silica sol-gel for the controlled release of antibiotics. II. The effect of
      synthesis parameters on the in vitro release kinetics of vanomycin.
AB  - Room temperature-processed silica sol-gel (xerogel) was investigated as a novel
      controlled release carrier of vancomycin for the treatment of osteomyelitis.
      Vancomycin-loaded xerogels were fabricated with varying water/alkoxysilane molar
      ratios and vancomycin concentrations. The goal of this study was to determine the
      effect of varying the aforementioned synthesis parameters on the daily in vitro
      release kinetics of vancomycin from the xerogel disks. A controlled, load
      dependent, long-term release of vancomycin was observed for all of the molar
      ratios that were used in the study (4, 6, and 10). Variations in the
      water/alkoxysilane molar ratio affected the release process extensively. A
      cumulative release of about 90% of the original amount of vancomycin was found
      for molar ratios 6 and 10 by 21 and 14 days, respectively. Only about 30% was
      released from xerogels with a molar ratio of 4 after 21 days of immersion. A
      first-order release stage was followed by a steady release stage for xerogels
      with molar ratios of 6 and 10, whereas zero-order release was observed for
      xerogels with a molar ratio of 4. The findings of this study indicate that the
      release kinetics of vancomycin from xerogel can be tailored by varying the
      xerogel synthesis parameters.

PMID- 11584810
TI  - Aldosterone 2001.

PMID- 11584812
TI  - Training basic surgical technique.

PMID- 11584811
TI  - Striatal and central extended amygdala parts of the interstitial nucleus of the
      posterior limb of the anterior commissure: evidence from tract-tracing techniques
      in the rat.
AB  - The interstitial nucleus of the posterior limb of the anterior commissure (IPAC)
      lies at the junction of the striatopallidal system and the lateral bed nucleus of
      the stria terminalis-central amygdaloid nucleus continuum (i.e., the central
      extended amygdala; EAc). Its efferent connections were investigated in the rat
      with anterograde (Phaseolus vulgaris leucoagglutinin) and retrograde (Fluoro-Gold
      and cholera toxin B subunit) tracers and compared with those of the central
      amygdaloid nucleus. Our anterograde tracing experiments reveal that the
      projections of the medial IPAC largely reciprocate its afferent connections
      (Shammah-Lagnado et al. [1999] Neuroscience 94:1097-1123) and are very similar to
      those of the medial part of the central amygdaloid nucleus. The lateral IPAC, on
      the other hand, innervates the pallidal complex, substantia nigra and retrorubral
      field. Local connections are found within medial IPAC and within lateral IPAC,
      but the two divisions are not interconnected. Our retrograde tracing experiments
      confirm that IPAC projections to EAc components, parabrachial area, and nucleus
      of the solitary tract originate chiefly from the medial division, whereas both
      medial and lateral divisions innervate the retrorubral field. Moreover, in
      sections processed for choline acetyltransferase, the strong projections from
      caudal IPACm to the posterior basolateral amygdaloid nucleus and the
      amygdalopiriform transition area were found to arise chiefly from cholinergic
      cells. Overall, our results suggest that the medial IPAC is intimately related to
      the EAc, whereas the lateral IPAC represents a striatal territory.

PMID- 11584813
TI  - Nasal strips and EIPH in the exercising Thoroughbred racehorse.

PMID- 11584814
TI  - Hyperpigmentation along the lines of Blaschko with associated chromosome 14
      mosaicism.

PMID- 11584815
TI  - Pediatric advocacy.
AB  - Advocacy is part of the job description of a pediatrician. There is a long
      history of pediatrician involvement in civil society. Like other skills in
      pediatrics, the skills required for advocacy activities are learnable. Anyone who
      can learn the Krebs cycle can learn how to be a child advocate. Being a child
      advocate is not always easy, but it is rewarding. The 1995 Nobel Prize in
      Chemistry was awarded to Rowland et al for their work in the description of the
      destruction of stratospheric ozone by chlorofluorocarbons. Having done the
      groundbreaking research, Rowland and Molina spent much time working to ban
      chlorofluorocarbons. When asked why they, as bench scientists, ventured out of
      the laboratory as advocates, Rowland stated, "If not me, who? If not now, when?"
      (personal communication, December 7, 2000).

PMID- 11584816
TI  - USA talks of war after more than 5000 killed in terrorist attacks.

PMID- 11584817
TI  - New York physicians respond to the terror, tragedy, and trauma.

PMID- 11584818
TI  - Attacks provide first major test of USA's national antiterrorist medical response
      plan.

PMID- 11584819
TI  - Presidential and Congressional responses as a nation reels after the attacks.

PMID- 11584820
TI  - Aid agencies withdraw staff from Afghanistan as refugees flee to the border.

PMID- 11584821
TI  - Contemplating the forensic medical implications of the attack.

PMID- 11584822
TI  - International gatherings of health leaders added to the casualties.

PMID- 11584823
TI  - The usefulness of functional assays for the prediction of acute graft-versus-host
      disease in HLA-identical sibling bone marrow transplantation.

PMID- 11584824
TI  - Case 6: benefits and risks of OKT3 treatment in renal transplantation.

PMID- 11584825
TI  - Long-term care in New York: innovation in care for elderly and disabled people.

PMID- 11584826
TI  - Imaging the less seriously head  injured child.

PMID- 11584827
TI  - Spacers   and   holding   chambers:   Not the last word, we hope--a reply.

PMID- 11584828
TI  - Health care in New York City: understanding and shaping change.

PMID- 11584829
TI  - Meeting future health and long-term care needs of an aging population.

PMID- 11584830
TI  - A vote of confidence: attitudes toward employer sponsored health insurance.

PMID- 11584831
TI  - Prescription drug costs for Medicare beneficiaries: coverage and health status
      matter.

PMID- 11584832
TI  - Assuring the healthy development of young children: opportunities for states.

PMID- 11584833
TI  - Equity in health care across five nations: summary findings from an international
      health policy survey.

PMID- 11584835
TI  - Juvenile idiopathic arthritis and uveitis: the classification conundrum.

PMID- 11584834
TI  - Localization of 5' and 3' ends of the ribosome-bound segment of template
      polynucleotides by immune electron microscopy.
AB  - Poly(U) with an average chain length of 40-70 nucleotides was modified at the 5'-
      or 3'-terminal residues with 2,4-dinitrophenyl derivatives. The modified poly(U)
      was used to form 30S.poly(U) or 70S.poly(U).Phe-tRNA complexes. Localization of
      the 5' and 3' ends of the template polynucleotide on the 30S subunit and the 70S
      ribosome was performed by immune electron microscopy using antibodies against
      dinitrophenyl haptens. The 5' and 3' ends of poly(U) (putative entry and exit
      sites of the message) were found in the same region both on the 30S subunit and
      the 70S ribosome. They were located on the dorsal side of the 30S subunit between
      the head and the body near the groove bordering the side ledge (platform).
      Comparison of the size of this region with the possible length of the
      polynucleotide chain covered by the ribosome allowed us to suggest that the
      message makes a 'U-turn" (or forms a 'loop') as it passes through the ribosome.

PMID- 11584836
TI  - Nine year follow-up study of morbidity and mortality in retinal vein occlusion.
AB  - PURPOSE: The aim of this study was to conduct a detailed retrospective follow-up
      of a large cohort of patients with retinal vein occlusion (RVO), examining
      morbidity and mortality, to investigate a possible relationship between RVO,
      large vessel disease and stroke, and to determine whether recurrence of RVO was
      influenced by treatment of associated medical conditions. METHODS: A follow-up
      study was undertaken in 1994 of all patients (n = 588) who presented to the
      medical ophthalmology clinics of the Birmingham and Midland Eye Hospital between
      1982 and 1989 with a definitive diagnosis of RVO. RESULTS: Follow-up data were
      obtained on 549 patients (93%). Results showed that recurrence of RVO in the same
      or fellow eye was decreased by more than half in the follow-up group (3.3%) when
      compared with the known recurrence rate at initial presentation (8.8%).
      Comparison of the deceased with the survivors showed that the deceased patients
      were significantly older (mean age 70.2 vs 63.4 years). The prevalence of
      rubeosis iridis and smoking were statistically significantly increased when
      comparing the deceased with the survivors (p < 0.016 and p < 0.008 respectively).
      The deceased had a higher prevalence of diabetes (15.8% vs 10.1%), and there was
      a trend towards increased clinically evident macrovascular disease in those
      patients who had died (23.2% vs 19.5%). Neither hypertension nor hyperlipidaemia
      predicted death, as the prevalence rates of the two conditions were similar in
      survivors and those who had died (60.0% vs 60.6% and 48.4% vs 53.3%). The
      percentage of patients taking antiplatelet drug therapy was not different in the
      two groups (36.8% vs 38.3%). Analysis of the causes of death of the RVO
      population (n = 95) compared with the causes of death in the West Midlands
      population as a whole, showed that the percentage of deaths from myocardial
      infarction in the RVO population was significantly higher (23.1% vs 14.4%, p <
      0.05). There was no statistical difference between the populations for ischaemic
      heart disease and stroke, although there was a trend for increased mortality from
      stroke (19% vs 13.5%). CONCLUSION: These data suggest a relationship between RVO,
      mortality and increased cardiovascular risk factors (smoking, diabetes and
      macrovascular disease), and support the possibility of an association between RVO
      and stroke. They also support the potential value of medical treatment of
      underlying medical conditions in preventing recurrence of RVO.

PMID- 11584837
TI  - Optic nerve head blood flow measurements in non-arteritic anterior ischaemic
      optic neuropathy.
AB  - PURPOSE: To determine whether a decrease in blood flow, measured by the
      Heidelberg retiinal flowmeter, can characterise a disc at risk and predict the
      occurrence of non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS:
      Blood flow, volume and velocity were measured in the optic nerve heads of 14
      unaffected fellow eyes of patients with unilateral NAION, and compared with those
      of the affected eyes and of the eyes of 7 age-matched healthy controls. RESULTS:
      The affected eyes were found to differ from the unaffected eyes in all three
      haemodynamic parameters. Flow (measured in arbitrary units) is the most important
      parameter to be taken into consideration. Blood flow was significantly lower in
      affected than in unaffected eyes (upper rim, p < 0.05; lower rim, p < 0.025). It
      was also significantly lower in the unaffected eyes than in the healthy control
      eyes (p < 0.005, upper and lower rims), and in the affected eyes than in the
      control eyes (p < 0.00005, upper and lower rims). CONCLUSION: Decreased blood
      flow in the optic nerve head may indicate a risk for NAION and be considered a
      characteristic of the disc at risk.

PMID- 11584838
TI  - Visual outcome after silicone oil removal and recurrent retinal detachment
      repair.
AB  - PURPOSE: Prospective analysis of the effect of removal of silicone oil (ROSO) in
      eyes with complicated retinal detachments and evaluation of the visual outcome
      following recurrent retinal detachment after silicone oil removal. METHODS: We
      evaluated 62 consecutive cases of ROSO over a 12 month period. All eyes had
      previously undergone silicone oil placement for complicated retinal detachments.
      All eyes undergoing scheduled ROSO over the time period of the study were entered
      and were reviewed post-operatively. RESULTS: Sixty-two eyes were entered into the
      study. Twenty-one of 62 (34%) developed recurrent retinal detachment following
      ROSO; 18 of these 21 recurrent detachments were reattached with one additional
      procedure and only 5 required replacement of the silicone oil. Ten of these 21
      eyes (48%) had improvement or stabilisation in final visual acuity compared with
      the presenting visual acuity. Overall, 39 eyes (63%) had improvement in vision
      following ROSO and 76% of all eyes had ambulatory visual acuity at the end of the
      follow-up period. Fourteen eyes required cataract extraction with ROSO to attain
      this final visual acuity. CONCLUSIONS: Overall, ROSO has a significant rate of
      recurrent retinal detachment, with a high reattachment rate with one additional
      procedure. Few of these eyes need the silicone oil replaced. Most eyes will
      retain ambulatory visual acuity even with multiple procedures in cases of
      complicated retinal detachments following ROSO even with recurrent retinal
      detachment.

PMID- 11584839
TI  - Psychological reactions and quality of life in patients with posterior uveal
      melanoma treated with ruthenium plaque therapy or enucleation: a one year follow
      up study.
AB  - PURPOSE: To investigate psychological reactions and quality of life among
      patients with posterior uveal melanoma. METHODS: Consecutive patients with uveal
      malignant melanoma (99/106), referred to St Erik's Eye Hospital 1995-1996,
      treated with rutheniuim plaque radiotherapy (n = 50) or enucleation (n = 49),
      were included in this non-randomised prospective comparative study.
      Questionnaires were completed before treatment (Hospital Anxiety and Depression
      Scale, HAD scale) and 2 and 12 months after diagnosis including the HAD scale,
      the Impact of Event Scale and the EORTC QLQ-C30. A disease-specific questionnaire
      was included 12 months after diagnosis. Between-group differences were analysed
      by chi-square, Student's t-test and ANOVA. RESULTS: A majority of the patients
      reported reduced 'Quality of Life' (72-85%), 'Emotional functioning' (60-74%) and
      'Cognitive functioning' (51-61%). 'Fatigue' was the most frequently reported
      symptom (61-72%) followed by 'Insomnia' (43-58%). Anxiety and depressive symptoms
      were relatively frequent up to 1 year after treatment, but the levels of anxiety
      decreased during the first year after treatment. Disease and treatment-related
      problems were reported in both treatment groups 1 year after diagnosis.
      Enucleated patients had more problems with appearance and judging distances,
      whereas those treated with radiotherapy reported vision impairment to a higher
      extent. CONCLUSIONS: Enucleated patients reported high levels of emotional
      distress, problems with appearance and judging distances during the first year
      after treatment. Patients treated with radiotherapy reported similar levels of
      quality of life and emotional problems, but more problems with visual impairment.
      These differences in impact on disease-related functioning should be taken into
      account when treatment options are discussed.

PMID- 11584840
TI  - Detection and prevalence of early diabetic retinopathy in juvenile diabetics with
      diabetes for 10 years or more.
AB  - PURPOSE: To compare clinical examination using green light with clinical
      examination using white light in detecting early diabetic retinopathy (DR) in
      juvenile diabetic patients with disease for 10 or more years. METHODS: All
      patients were examined clinically using both green light and white light to
      determine the presence of DR. Each patient underwent seven-field fundus
      photography, which was used as the defined standard against which the clinical
      examinations were compared and also to determine the prevalence of DR. Data on
      age at diagnosis, duration of diabetes mellitus, recent HbA1c levels, treatment
      for systemic hypertension and microalbuminuria were obtained from medical
      records. RESULTS: When compared with the defined standard, fundal examination
      with green light was more sensitive, more specific and had higher predictive
      values than examination with white light in the detection of early DR. The
      overall prevalence of DR was 44%, which in all cases was classified as minimal to
      mild background DR. Patients with DR had significantly higher mean HbA1c levels
      than those without (p = 0.016). There was no significant association between the
      prevalence of DR and age at time of examination or diagnosis, duration of
      diabetes, patient gender, microalbuminuria levels or treatment for systemic
      hypertension. CONCLUSION: Fundal examination with green light is better than
      white light in detecting early DR in juvenile diabetics with duration of disease
      of 10 years or more. Furthermore the presence of DR is associated with poorer
      diabetic control. Due to coincident lifestyle changes and the probability of long
      duration of disease, accurate detection of early DR in juvenile diabetics with
      diabetes for over 10 years is important.

PMID- 11584841
TI  - Development of proliferative retinopathy in patients with long-standing insulin
      dependent diabetes mellitus.
AB  - PURPOSE AND METHOD: Some patients with long-standing insulin-dependent diabetes
      mellitus (IDDM) develop little or no retinopathy. Using a clinic-based
      questionnaire and examination, we investigated a group of patients with over 40
      years or more of IDDM who had been followed up at the King's Diabetes Centre for
      an average of 40 years. We compared those who had developed proliferative
      diabetic retinopathy during their disease with those with minimal or no
      retinopathy. RESULTS: The study did not find any statistically significant
      differences between the two groups to suggest why some long-term insulin
      dependent diabetics develop little retinopathy. Those who developed sight
      threatening retinal complications did so at an average of 35 years after
      diagnosis and it resulted in little visual disablement. Very few patients in
      either group had developed other significant complications. CONCLUSIONS: This
      study details an interesting group of patients with long-term IDDM mellitus with
      a mean follow-up period of 40 years. Some patients with long-standing IDDM
      develop little or no retinopathy. With the advent of community ophthalmic
      screening, these patients are now rarely seen in the eye clinic. Those who did
      develop retinal complications and required treatment have remarkably little
      visual disablement. However, these complications developed late in the history of
      their disease, emphasising the need for continued screening.

PMID- 11584842
TI  - Endogenous Klebsiella endophthalmitis.
AB  - PURPOSE: To report 4 cases of endogenous Klebsiella endophthalmitis. This disease
      is a rare but devastating complication of Klebsiella sepsis. Familiarity with its
      varied clinical presentations would aid in early diagnosis and institution of
      appropriate therapy. METHODS: We report 5 eyes of 4 patients with endogenous
      Klebsiella endophthalmitis from December 1995 to September 1996 and review the
      literature regarding previously successfully treated cases. RESULTS: The mean age
      of the patients was 67.5 years (range 37-85 years). One patient had bilateral
      involvement. At presentation, 3 eyes had a visual acuity of no perception of
      light (NPL) and the 1 patient with bilateral involvement had an acuity of
      counting fingers in one eye and 20/40 in the other. The primary source of sepsis
      was the pulmonary system in 2 patients, the hepatobiliary system in 1 patient and
      the urinary tract in 1 patient. One patient had coexisting diabetes mellitus. Two
      patients had a pupillary hypopyon. Local and systemic treatment with an
      aminoglycoside and cephalosporin was initiated. Despite treatment, 2 eyes
      remained NPL. One eye developed a globe perforation and was eviscerated. The
      patient with bilateral involvement was treated within 8 h and recovered fully
      with a final visual acuity of 20/20 in both eyes. CONCLUSION: It is important to
      have a high index of suspicion in patients with septicaemia presenting with
      intraocular inflammation, especially in diabetics with suppurative liver disease,
      urinary tract infection or pulmonary infection. As the visual prognosis for
      patients with Klebsiella endophthalmitis is generally poor, early diagnosis and
      treatment with intravenous and intravitreal antibiotics may improve the visual
      outcome.

PMID- 11584843
TI  - Non-syndromic posterior lenticonus a cause of childhood cataract: evidence for X
      linked inheritance.
AB  - PURPOSE: When an X-linked pedigree of posterior lenticonus with cataract was
      identified further evidence for X-linked inheritance of this condition was
      sought. METHODS: Forty-three cases of posterior lenticonus were identified from a
      database of 354 children with cataract. Two children with the X-linked syndromes
      of Lowe and Nance-Horan and 3 children with Fanconi syndrome have been excluded
      from further analysis. None of the children was deaf. None of the non-syndromic
      cases had microcornea. RESULTS: There were 38 cases of non-syndromic posterior
      lenticonus (approximately 11%). There were 15 children from 13 pedigrees and 23
      apparently sporadic cases. Of the 106 cases on the database with unilateral
      cataract 15 had posterior lenticonus (approximately 14%). Eleven of 13 pedigrees
      were compatible with X-linked inheritance or autosomal dominant inheritance with
      variable expression. However, in 2 pedigrees there was father to son
      transmission. CONCLUSIONS: Posterior lenticonus is a common cause of unilateral
      infantile cataract, but is thought to be a rare cause of bilateral cataracts.
      This study suggests that posterior lenticonus is responsible for a significant
      proportion of childhood cataracts (approximately 14% of unilateral and
      approximately 9% of bilateral cases). Posterior lenticonus is generally thought
      to occur as a sporadic condition. This study demonstrates that there is a family
      history of early-onset cataract in a significant number of bilateral cases
      (approximately 58%).

PMID- 11584844
TI  - Long-term follow-up of lid surgery for trichiasis in the Gambia: surgical success
      and patient perceptions.
AB  - BACKGROUND: Surgery is an important component of the SAFE strategy which has been
      shown to improve visual acuity. There are limited data on long-term surgical
      success and patient perceptions and satisfaction. A sample of patients from the
      Gambia who had undergone previous lid surgery for trichiasis were therefore
      examined for recurrence of trichiasis and interviewed for patient satisfaction.
      METHODS: Health centre surgical records and community screening were used to
      identify patients who had undergone previous lid surgery. Consenting patients
      were examined and a questionnaire administered. Kaplan-Meier survival plots were
      constructed for recurrence of trichiasis. RESULTS: Sixty-five subjects were
      recruited. Median age at surgery was 50 years. Median time since surgery was 7
      years. Fifty-two of 115 (45%) operated eyes were free of trichiasis at follow-up
      and 23 of 65 (35%) patients had not suffered recurrent trichiasis in an operated
      eye. Median time from surgery to recurrence of trichiasis was estimated as 10.0
      years (95% CI 3.7-16.3). Recurrent trichiasis was not significantly associated
      with visual impairment or blindness at follow-up. The following patient
      perceptions were reported: satisfaction with surgery (88%), less discomfort than
      before surgery (93%), improved vision (83%), work easier (38%), worth the
      expenditure (94%), would recommend it to others (93%), had recommended it to
      others (38%), experienced intra-operative pain (26%) and experienced post
      operative pain (26%). CONCLUSION: Factors affecting surgical success, including
      surgical technique and re-exposure to infection, are discussed. This study
      provides important preliminary data for programme planners but larger prospective
      studies are required.

PMID- 11584845
TI  - Up-shoot in adduction has no prognostic value for decompensation in refractive
      accommodative esotropia.
AB  - PURPOSE: To assess whether up-shoot (elevation) in adduction has any prognostic
      value for the functional outcome of binocular vision in fully refractive
      accommodative esotropia (RAET). METHODS: A retrospective study was performed on
      58 patients initially diagnosed with RAET who were followed for at least 4 years.
      RESULTS: Without glasses, up-shoot in adduction with or without a V pattern was
      detected in 22 of 51 patients who maintained normal binocular alignment during
      the whole follow-up and in 3 of 7 patients who lost normal binocular vision and
      showed a manifest esotropia despite glasses at any time of the follow-up. Up
      shoot in adduction was still present through glasses only in 3 patients among
      these 25 cases. Two of these remained fully compensated with glasses during the
      considered period. The third case developed up-shoot in adduction after
      decompensation of a previously compensated strabismus. CONCLUSIONS: Up-shoot in
      adduction is not a common sign in RAET. When present, it does not necessarily
      represent a negative prognostic sign for preservation of normal binocular vision
      through glasses in this condition. Up-shoot in adduction can develop after the
      loss of alignment in some decompensated patients. There is therefore no evidence
      in favour of a cause-effect relationship between up-shoot in adduction and loss
      of binocularity in RAET.

PMID- 11584846
TI  - Efficacy and complications of dose increments of botulinum toxin-A in the
      treatment of horizontal comitant strabismus.
AB  - PURPOSE: To investigate the efficacy and complications associated with dose
      increments of botulinum toxin-A (BTA) for comitant horizontal strabismus
      patients. METHODS: Twenty-five esotropic (ET) and 45 exotropic (XT) patients
      received 2.5-20 U of BTA injection. Parameters for achieving less than 10 prism
      dioptres (pd) of horizontal deviation and percentage correction of the
      pretreatment deviation were assessed for injections of less than 10 U and more
      than 10 U of BTA. Induced ptosis and vertical deviation were examined within and
      after 6 months of follow-up. RESULTS: The mean pretreatment deviations were 38.6
      +/- 2.5 pd and 37.6 +/- 1.9 pd for the ET and XT groups, respectively. After
      receiving 1.6 and 1.5 injections on average, improvement to less than 10 pd at
      the primary position occurred in 32% of ET and 22% of XT patients; the difference
      was not statistically significant. The percentage corrections of the ET patients
      were 41.4 +/- 9.3% and 36.9 +/- 5.6% in those treated with less than 10 U and
      more than 10 U of BTA respectively; the difference between the two groups was
      insignificant. For the XT patients the values were 42.1 +/- 7.4% and 28.9 +/-
      3.5% respectively, which also were not statistically significantly different.
      Frequency of induced ptosis was more common in ET than XT patients (p = 0.01) and
      this difference was more pronounced with increased doses of BTA (7.7% in ET and
      5.3% in XT patients with less than 10 U of BTA, and 24.0% in ET and 4.3% in XT
      patients with more than 10 U of BTA). Ptosis resolved completely within 6 weeks
      in all cases. Induced vertical deviation with less than 10 U of BTA was
      encountered in one case of ET (11.1%, 9 pd) and in another case of XT (8.3%, 4
      pd), increasing to 60.0% (2-20 pd) and 38.8% (4-16 pd) respectively with more
      than 10 U of BTA injection. In about a year, induced vertical deviation resolved
      in approximately 40%, and decreased in 30% of the cases. CONCLUSION: Increasing
      the dose of BTA is clinically effective in larger deviations, although
      statistically indifferent, especially in ET compared with XT. However, an
      increased dose is accompanied by increased incidence of induced ptosis and
      vertical deviation. Ptosis is temporary, but vertical deviation may persist for a
      long time and may present a cosmetic problem for some patients when more than 10
      U of BTA is used.

PMID- 11584847
TI  - Measurements for horizontal extraocular muscle surgery from the suture site:
      outcome and influencing factors.
AB  - BACKGROUND: Measurement of recession in strabismus surgery is performed either
      from the limbus or from the muscle insertion. These measurement methods may
      result in inaccuracies that may influence the outcome of the procedure. We
      prospectively evaluated the outcome of recessions measured from the extraocular
      muscle suture site to its insertion in an incidence cohort. METHODS: Thirty-six
      consecutive surgical procedures for infantile esotropia and 23 for constant
      exotropia were performed in which measurements were performed from the suture
      site. A successful surgery for esotropia was defined as an orthophoria of up to
      +10 prism dioptres of deviation for non-accommodative targets at a distance of 20
      feet, measured by cover and prism test. A successful surgery for exotropia was
      defined as a residual deviation between -10 and +10 prism dioptres. The
      statistical significance of the outcome influencing factors was assessed by chi
      square test. RESULTS: Six weeks following surgery, 28 procedures (78%) for
      infantile and non-accommodative esotropia and 19 procedures (83%) for exotropia
      were successful. At the end of the follow-up period (mean 13.7 months +/- 9.4 for
      esotropia and 11.6 months +/- 12.8 for exotropia), the success rate was 77% for
      esotropia and 75% for exotropia. Prematurity and mental retardation in esotropia,
      exotropia with pre-operative deviations larger than -45 prism dioptres and
      amblyopia in exotropia were related to unfavourable outcome (p < 0.05).
      CONCLUSIONS: Measurement for muscle recession can be performed from the suture
      site. The outcome is comparable to the outcome when measurements are performed
      from the limbus or the insertion, probably due to the incidence cohort.
      Refinement of the technique and defining other factors influencing the outcome of
      strabismus surgery may improve the outcome.

PMID- 11584848
TI  - Ocular manifestations of hindbrain-related syringomyelia and outcome following
      craniovertebral decompression.
AB  - PURPOSE: To analyse and evaluate associated ocular symptoms and signs in
      hindbrain-related syringomyelia and their response to treatment. METHODS: From a
      database of 275 patients treated in a single institution for hindbrain hernia and
      syringomyelia, 39 patients (14%) had ocular symptoms and signs. Only 31 patients
      were included in this study; the remainder were excluded due to inadequate follow
      up information. All patients had confirmed evidence of hindbrain-related
      syringomyelia with MRI scan or CT myelogram. Treatment included craniovertebral
      decompression or ventriculo-peritoneal shunting. The mean follow-up was 23
      months. RESULTS: In addition to the well-recognised sign of downbeat nystagmus,
      classically associated with foramen magnum abnormalities, a number of other
      ophthalmic features were identified. Symptoms included diplopia, oscillopsia,
      tunnel vision and difficulty in lateral gaze. Signs included nystagmus (downbeat,
      horizontal, rotatory, and combinations), strabismus, disc pallor, anisocoria,
      ptosis and field defect. Patients were categorised into two groups depending on
      whether the ocular features were manifest at first presentation (group 1, n = 14)
      or developed later in the course of the disease (group 2, n = 17). The delay in
      diagnosis from first presentation was 5 and 6 years respectively. All patients
      underwent surgery. Craniovertebral decompression was performed in 13 patients in
      group 1 and in 15 patients in group 2. Ventriculo-peritoneal shunt was inserted
      in 1 patient in group 1 and in 3 patients in group 2, for the associated
      hydrocephalus. Following surgery, 100% of patients in group 1 and 82% of patients
      in group 2 had complete or partial resolution of their ocular symptoms and signs.
      CONCLUSIONS: The presence of unexplained ophthalmic features such as nystagmus or
      oscillopsia should alert one to the potential diagnosis of hindbrain-related
      syringomyelia. Delay in diagnosis is often associated with poorer outcome.
      Surgical treatment can offer excellent results for these patients.

PMID- 11584849
TI  - Hepatitis C virus infection is not associated with a marked increase in the
      prevalence of ophthalmic morbidity.
AB  - BACKGROUND: Chronic infection with the hepatitis C virus has been reported to
      cause a wide variety of ophthalmic lesions. The incidence and significance of
      these lesions in an unselected population has not been assessed. METHODS: We
      studied a group of unselected patients with chronic hepatitis C and performed a
      full ophthalmic examination on each. As a control group we studied patients with
      chronic hepatitis B infection. RESULTS: In 25 patients with chronic hepatitis C
      we found no increase in the prevalence of significant ocular disease when
      compared with a cohort of patients with chronic hepatitis B. CONCLUSION: Chronic
      heptatitis C does not cause any marked increase in the incidence of ocular
      disease.

PMID- 11584850
TI  - Improvement of the ocular surface using hypotonic 0.4% hyaluronic acid drops in
      keratoconjunctivitis sicca.
AB  - BACKGROUND: The ocular surface changes of keratoconjunctivitis sicca (KCS) could
      be the result of the effect of an altered tear film on the epithelial
      environment. PURPOSE: To evaluate the possibility of improving the environmental
      conditions of the ocular surface by lowering tear osmolarity, increasing tear
      film volume and stabilising the tear film. Also, to study the effect of such an
      improvement on the epithelial cells of the ocular surface. METHODS: One hundred
      and thirty-five patients with a diagnosis of KCS were treated on a randomised
      basis with either unpreserved hypotonic 0.4% hyaluronic acid (HHA) eye drops or
      0.3% hydroxypropylmethylcellulose plus 0.1% Dextran 70 (HPMC) eye drops 6 times a
      day for 60 or 90 days. In all patients a Schirmer I test, break-up time (BUT),
      ocular surface staining with 1% Bengal Rose, or 2% fluorescein, as well as
      subjective symptoms, were recorded before and 15, 30 and 60 days after the
      beginning of the study. Patients were divided into three subgroups and the effect
      of the treatment was studied using three different techniques: the tear ferning
      test, conjunctival impression cytology and tear osmolarity measurement. RESULTS:
      Improvements in BUT, vital staining, Schirmer I and symptoms were recorded in
      both groups of treatment, with significant differences for patients treated with
      0.4% HHA. On day 60, 30 min after installation: tear ferning patterns changed
      from 100% pathological (types III-IV) to 93% physiological (types I-II) in the
      0.4% HHA group and from 100% pathological to 78% physiological in the 0.3% HPMC
      group (p < 0.01 between groups). Tear osmolarity shifted from 353 +/- 23 to 305
      +/- 6 mosmol/l in the 0.4% HHA group and from 346 +/- 15 to 336 +/- 8 mosmol/l in
      the 0.3% HPMC group (p < 0.001 between groups). On day 90, the impression
      cytology score improved from 1.2 to 1.9 in the 0.4% HHA group while it did not
      change in the 0.3% HPMC group (p < 0.05 between groups). CONCLUSION: In KCS
      appropriate treatment with a hypotonic 0.4% HHA tear substitute can change the
      tear environment and results in improvement of the epithelial conditions of the
      ocular surface.

PMID- 11584851
TI  - Effect of nitric oxide on proliferation of human retina pigment epithelial cells.
AB  - PURPOSE: To investigate the effects of exogenous and endogenous nitric oxide (NO)
      on the proliferation of human retina pigment epithelial (RPE) cells. METHODS: We
      stimulated cultured human RPE cells with 3-morphosydnonimine (SIN-1) to analyse
      the effect of exogenous NO. Incubation with a cytokine cocktail (interleukin 1
      beta + interferon gamma + tumour necrosis factor alpha) plus lipopolysaccharide
      (LPS) induced cells to synthesise NO endogenously. The cultures were then
      incubated for 48 h, after which the cells were stained with crystal violet and
      absorbance at 550 nm was measured spectrophotometrically. RESULTS: SIN-1
      inhibited human RPE cell proliferation, while haemoglobin, an NO inhibitor,
      almost completely blocked the inhibitory effect. On the other hand, treatment
      with the cytokine cocktail plus LPS did not inhibit RPE cell proliferation.
      CONCLUSION: These findings confirm that exogenous NO inhibits human RPE cell
      proliferation, while endogenous NO has no such blocking effect.

PMID- 11584852
TI  - Lightning-induced cataract.

PMID- 11584853
TI  - Alkali injury complicated by choroidal neovascularisation.

PMID- 11584854
TI  - Permanent corneal limbal stem cell dysfunction following radiotherapy for orbital
      lymphoma.

PMID- 11584855
TI  - Allergic contact fingertip dermatitis secondary to proxymetacaine in an
      ophthalmologist.

PMID- 11584856
TI  - Brimonidine tartarate 0.2% (Alphagan) associated granulomatous anterior uveitis.

PMID- 11584857
TI  - Pupil function after phacoemulsification and extracapsular cataract surgery.

PMID- 11584858
TI  - Optic neuropathy in a patient with chronic inflammatory demyelinating
      polyneuropathy.

PMID- 11584859
TI  - Extensive globe rupture from blunt trauma: a case with a hope.

PMID- 11584860
TI  - Bilateral diabetic papillopathy associated with optic disc neovascularisation.

PMID- 11584861
TI  - Severe hypotony following cataract extraction in a patient on latanoprost.

PMID- 11584862
TI  - Neovascularisation in a patent chorioretinal anastomosis.

PMID- 11584863
TI  - Partial facial paralysis following temporal artery biopsy.

PMID- 11584864
TI  - Presumed interferon-associated bilateral macular arterial branch obstruction.

PMID- 11584865
TI  - Guidelines to the DVLA regarding the standard for driving visual fields.

PMID- 11584866
TI  - Low need for intervention at the first day review after uncomplicated
      phacoemulsification.

PMID- 11584867
TI  - Scleral dellen complicating primary pterygium excision.

PMID- 11584868
TI  - Ophthalmologic confirmation of referrals for suspected cases of glaucoma
      initiated by optometrists.

PMID- 11584869
TI  - Extracapsular cataract surgery.

PMID- 11584870
TI  - Pharmacologic approaches to the management of alcoholism.
AB  - Our understanding of alcohol craving, both as a cause for chronic abuse and
      relapse and as a target for intervention, has been refined significantly in
      recent years. For example, craving experienced during alcohol withdrawal may be
      mediated by gamma-aminobutyric acid (GABA) and glutamate receptor mechanisms,
      whereas the memory of the rewarding aspects of alcohol may be mediated by
      dopamine, opiate, and glutamate systems. Therefore, pharmacologic treatments for
      alcohol dependence may be targeted to numerous pathways. This article will
      discuss animal and clinical studies of the opioid antagonists (primarily
      naltrexone), acamprosate, and disulfiram. The side effects and treatment
      recommendations for each drug will also be reviewed.

PMID- 11584871
TI  - The role of selective serotonin reuptake inhibitors in reducing alcohol
      consumption.
AB  - Preclinical and clinical studies demonstrated an inverse relationship between
      serotonergic activity and alcohol consumption. The selective serotonin reuptake
      inhibitors (SSRIs) fluoxetine, citalopram, and fluvoxamine have subsequently been
      examined for their ability to reduce alcohol consumption in alcoholic subjects.
      Interindividual variability in response to SSRIs is large, with reductions in
      alcohol consumption ranging from 10% to more than 70%. Several factors, including
      gender, alcoholic subtype, and extent of drinking, appear to affect the treatment
      efficacy of the SSRIs. A significant challenge for researchers is to identify the
      subject variables that predict treatment response, providing a basis for guiding
      alcohol-dependent individuals to the treatment that is most likely to be
      effective for them. This article reviews the available clinical studies,
      discusses possible mechanisms of action for the SSRIs, and describes a model for
      predicting treatment responses in alcoholic subjects.

PMID- 11584872
TI  - The use of selective serotonin reuptake inhibitors in treating alcoholic
      subtypes.
AB  - The usefulness of selective serotonin reuptake inhibitors (SSRIs) to treat
      alcohol dependence continues to be a subject of debate. Most recently,
      investigations have tried to predict whether a given patient will respond to
      SSRIs in terms of reducing excessive alcohol drinking. The subtyping of alcohol
      dependent individuals has ranged from relatively simple classifications (e.g.,
      presence of comorbid depression) to more complex classifications (e.g., potential
      to have abnormalities in serotonin [5-HT] neurotransmission). Although only a few
      studies have been completed, results thus far indicate that alcoholic subgroups
      are differentially responsive to 5-HT pharmacotherapy with respect to drinking
      related outcomes. In addition, there are preliminary results encouraging the use
      of SSRIs in combination with other medications for treating alcohol dependence in
      patients with and without comorbid psychiatric disorders. Information from these
      studies is promising, suggesting the need for further investigation.

PMID- 11584873
TI  - Comorbid alcoholism and depression: treatment issues.
AB  - Unless there is decisive professional intervention, people who suffer from both a
      depressive disorder and alcoholism are at great risk of chronic impairment, both
      at home and in the workplace; persistent symptomatic misery; and premature death.
      Untreated alcoholism intensifies depressive states, decreases responsiveness to
      conventional therapeutics, and increases the likelihood of suicide, suicide
      attempts, and other self-destructive behavior. During the past decade, evidence
      has emerged from placebo-controlled studies supporting the utility of tricyclic
      antidepressants and selective serotonin reuptake inhibitors (SSRIs) for treatment
      of depressed alcoholics. The superior safety and tolerability of SSRIs provide
      strong justification for their first-line use despite higher drug acquisition
      costs. Evidence has similarly emerged concerning the use of several novel
      pharmacotherapies and focused psychotherapies for people with alcoholism. These
      newer therapeutic options complement more traditional intervention such as
      chemical dependence counseling, disulfiram, and Alcoholics Anonymous so that it
      is now possible for a majority of depressed alcoholics to be treated effectively.
      The availability of effective treatments provides further impetus for health care
      professionals to improve recognition of comorbid alcoholism and depressive
      disorders. Improved recognition and treatment will save lives, and the benefits
      are likely to extend across generations.

PMID- 11584874
TI  - Alcohol abuse and alcoholism: an overview.
AB  - Alcoholism and alcohol abuse rank among the top 3 psychiatric disorders in the
      United States. These disorders are associated with significant medical and
      economic consequences. Furthermore, studies consistently show that an investment
      in addiction treatment leads to overall cost savings for society. Recent work has
      identified specific effects of alcohol on several neurotransmitter systems,
      including gamma-aminobutyric acid, serotonin, dopamine, and the opioid receptors.
      These findings suggest that multiple pharmacologic interventions may be useful
      for the treatment of alcohol addiction. This article reviews the clinical use of
      naltrexone and discusses psychosocial programs to enhance treatment retention and
      adherence.

PMID- 11584875
TI  - Treatment of alcohol-dependent outpatients with acamprosate: a clinical review.
AB  - Acamprosate (calcium acetyl-homotaurine) is a synthetic compound whose chemical
      structure resembles that of homotaurine, a naturally occurring amino acid.
      Acamprosate acts centrally and appears to restore the normal activity of
      glutaminergic neurons, which become hyperexcited as a result of chronic alcohol
      exposure. Although not yet approved for use in the United States, acamprosate has
      been available by prescription in France since 1989 and is now available in many
      other countries throughout the world. This article reviews data from all
      published double-blind, placebo-controlled clinical trials of acamprosate among
      alcohol-dependent outpatients. Overall, patients treated with acamprosate
      exhibited a significantly greater rate of treatment completion, time to first
      drink, abstinence rate, and/or cumulative abstinence duration than patients
      treated with placebo. The drug's reliable effect on prolonging abstinence, in
      conjunction with an excellent safety profile, suggests that acamprosate may be
      useful for a broad range of patients with alcohol dependence.

PMID- 11584876
TI  - Motivational and cognitive influences on affective priming in adulthood.
AB  - This research examined age differences in the impact of affective primes on
      judgments about neutral stimuli. When participants were unaware that the primes
      had been presented, age differences were nonexistent, with individuals of all
      ages producing likability judgments consistent with the valence of the prime. In
      contrast, when awareness of the primes was maximized, prime influences were
      virtually nonexistent in the youngest participants, but prime influences
      increased with participants' age. In addition, the impact of the primes was
      differentially affected by an individual's need for simple structure. Need for
      structure did not influence the performance of young and middle-aged
      participants, but prime effects increased with need in the oldest participants.
      It is argued that the stronger predictive validity of need for structure with age
      is due to aging-related changes in personal resources (both social and cognitive)
      and/or a closer mapping of individual characteristics onto need with age.
      Regardless of source, the results argue for closer consideration of motivational
      factors in determining age differences in performance.

PMID- 11584877
TI  - Reducing cardiovascular stress with positive self-stereotypes of aging.
AB  - We examined whether aging self-stereotypes, or older individuals' beliefs about
      elderly people, can influence cardiovascular function. Older individuals were
      subliminally exposed to either positive or negative aging stereotypes. Then all
      participants faced mathematical and verbal challenges. Those exposed to the
      negative aging stereotypes demonstrated a heightened cardiovascular response to
      stress, measured by systolic blood pressure, diastolic blood pressure, and heart
      rate, compared with those exposed to positive aging stereotypes. The aging
      stereotypes appeared to influence the outcome variable of skin conductance in the
      same way. It appears that the negative aging stereotypes acted as direct
      stressors, whereas the positive aging stereotypes reduced cardiovascular stress.
      These findings indicate that negative aging stereotypes may contribute to adverse
      health outcomes in elderly persons without their awareness. The results also
      suggest that positive aging stereotypes could be used in interventions to reduce
      cardiovascular stress.

PMID- 11584878
TI  - Age equivalence in feeling-of-knowing experiences.
AB  - Three studies investigated potential age-related differences in the reliance of
      healthy young and older adults on trace-access and inferential mechanisms in
      making feeling-of-knowing (FOK) judgments. In Experiment 1 young and older adults
      attempted to retrieve referents of rare-word definitions presented in a self
      paced questionnaire. Recall failures were followed by FOK ratings and a report of
      partial knowledge of referent characteristics. Gamma coefficients revealed age
      equivalence in FOK accuracy, and the number of recall attempts and FOK ratings
      did not vary by age. Older adults reported fewer partial characteristics and made
      more commission errors, which suggests reliance on inferential mechanisms in
      addition to direct recall of target information. Experiments 2 and 3 examined age
      related differences in reliance on trace-access or inferential processes via the
      influence of type of information primed prior to speeded recall attempt. Contrary
      to hypothesis, the influence of prime type did not vary by age. Reliance on trace
      access and inferential mechanisms of FOK does not appear to vary by age.
      Individuals can be forced to rely on trace-access mechanisms for speeded FOK
      judgments.

PMID- 11584879
TI  - Illusory correlation and group impression formation in young and older adults.
AB  - This study investigated whether a greater illusory correlation bias is present in
      older adults' memory and evaluative judgment for majority and minority social
      groups and, if so, whether this bias might be due to an age-related decline in
      the ability to engage in on-line processing of group-trait information. Young and
      older adults read desirable and undesirable trait adjectives about the members of
      2 groups under either no-distraction or distraction conditions. Group A had twice
      as many members as Group B and, for both groups, desirable traits occurred twice
      as often as undesirable traits. Afterwards, participants completed group-trait
      memory and evaluative judgment tasks. Greater illusory correlation in memory and
      evaluative judgment after distraction suggested that diverting resources to
      competing tasks produced deficits in both memory for specific group-trait
      information and on-line group impression formation. Older adults' memory for
      specific group-trait information was disrupted more by distraction than was young
      adults' memory. However, there were no age differences in evaluative judgment
      after either distraction condition, suggesting that on-line impression formation
      activities remain intact in old age. These findings are interpreted within the
      framework of fuzzy trace theory.

PMID- 11584880
TI  - Social conditions and distress in elderly persons: findings from the MacArthur
      Studies of Successful Aging.
AB  - The purpose of this study was to determine separate and joint associations of
      race/ethnicity and socioeconomic status (SES) with psychological distress among
      older high-functioning adults and to examine 2 psychosocial resources that may
      explain these associations. Participants were 70-79-year-old individuals (n =
      1,189) participating in the MacArthur Studies of Successful Aging program, a 3
      site study of community-dwelling men and women. Participants represented the top
      third of their peers in terms of functional ability in 1988. Additive and
      interactive models were used to examine cross-sectional associations among
      race/ethnicity, SES, and distress. Although decreases in distress generally occur
      with aging, findings suggest that social structural factors can influence
      distress even among elderly people. Blacks were less distressed than Whites when
      SES was controlled. There was a gradient between education and distress among
      Whites but not among Blacks. Measures of social support and control did not
      mediate effects of race/ethnicity on distress. These results differ from those of
      previous studies and indicate that age and functional status should be considered
      in examinations of relationships among race/ethnicity, SES, and distress.

PMID- 11584881
TI  - Predictors of institutionalization of cognitively impaired elders: family help
      and the timing of placement.
AB  - Although predictors of nursing home placement have attracted a good deal of
      attention in gerontological research, the type and amount of family assistance
      offered to caregivers prior to institutionalization has not been extensively
      examined. This study analyzed the impact of family help on the timing of
      placement among cognitively impaired care recipients. Using longitudinal data
      from the Adult Day Care Collaborative Study, an event-history analysis was
      performed to determine the effects of family help after sociodemographic
      characteristics, caregiving stressors, and indicators of caregiver well-being
      were taken into account. Results showed that caregivers were far less likely to
      institutionalize their relatives when family members provided overnight help and
      assisted with activities of daily living care. These findings suggest that
      specific types of family help play an important role in delaying nursing home
      placement among older adults suffering from dementia.

PMID- 11584882
TI  - Marital quality and psychological adjustment to widowhood among older adults: a
      longitudinal analysis.
AB  - OBJECTIVES: This study examined whether psychological adjustment to widowhood is
      affected by three aspects of marital quality--warmth, conflict, and instrumental
      dependence-assessed prior to the loss. METHODS: The Changing Lives of Older
      Couples (CLOC) is a prospective study of a two-stage area probability sample of
      1,532 married individuals aged 65 and older. The CLOC includes baseline data on
      marital quality and mental health and data on grief, anxiety, and depression
      collected 6, 18, and 48 months after spousal loss. RESULTS: Widowhood was
      associated with elevated anxiety among those who were highly dependent on their
      spouses and lower levels of anxiety among those who were not dependent on their
      spouses. Levels of yearning were lower for widowed persons whose relationships
      were conflicted at baseline and higher for those reporting high levels of marital
      closeness and dependence on their spouses. Women who relied on their husbands for
      instrumental support had significantly higher levels of yearning than men who
      depended on their wives. DISCUSSION: The findings contradict the widespread
      belief that grief is more severe if the marriage was conflicted and suggest a
      more complex relationship between bereavement and characteristics of the
      marriage.

PMID- 11584883
TI  - Relationship of activity and social support to the functional health of older
      adults.
AB  - OBJECTIVES: According to J. W. Rowe and R. L. Kahn (1997), successful aging is
      the combination of low probability of disease, high functioning, and active
      engagement with life. The purpose of this study was to assess the relationship
      between active engagement with life and functioning in a convenience sample of
      community-dwelling adults aged 65 and older. METHODS: In this cross-sectional
      study, 244 members of an organization for older adults were mailed a survey
      containing the Activity Checklist and the Social Support Inventory as measures of
      engagement with life and the SF-12 Health Survey as a measure of functioning.
      RESULTS: Hierarchical linear regression showed that maintenance of instrumental,
      social, and high-demand leisure activities was associated with higher physical
      health scores and maintenance of low-demand leisure activities was associated
      with lower physical health scores. Maintenance of low-demand leisure activities
      was associated with higher mental health scores. DISCUSSION: If changes in
      potentially modifiable risk factors such as activity are associated with the
      beginning of functional decline, early intervention may be possible before
      disability ensues, thus reducing the risk of disability and ultimately health
      care costs.

PMID- 11584884
TI  - Organizations' environment and retirement: the relationship between women's
      retirement, environmental munificence, dynamism, and local unemployment rate.
AB  - OBJECTIVES: Low munificence and high dynamism of an industry's environment and
      high local area unemployment rates were assumed to indicate uncertainty and
      influence retirement. It was predicted that, while controlling for personal
      variables, rates of retirement would vary across industries, that munificence
      would have a negative relationship with retirement, and that dynamism and
      unemployment rate would have positive relationships with retirement. METHODS: The
      study relies on four waves (from 1986 to 1992) of data from the National
      Longitudinal Survey's Mature Women Cohort, and logistic regression was used to
      examine the extent of the proposed relationships. RESULTS: Retirement rate varied
      across industries and had a positive relationship with munificent environments,
      but retirement was not related to dynamism or unemployment rates. CONCLUSIONS:
      The results suggest that environmental factors may influence retirement timing.
      Additional theoretical and empirical work is suggested to help sort out direct
      environmental effects and possible moderating third variables.

PMID- 11584885
TI  - Socioeconomic gradient in old age mortality in Wuhan, China.
AB  - OBJECTIVES: The vast majority of studies on socioeconomic status (SES) and old
      age mortality are based on data derived from developed nations. This research
      examined the SES differentials in old age mortality in China, a developing
      nation. METHODS: Hazard rate models in conjunction with ordinary least squares
      and logistic regression analyses were used to ascertain the gross, direct,
      indirect, and interaction effects of SES on mortality during a 3-year period in a
      probability sample of 2,943 persons aged 60 years or older in Wuhan, China.
      RESULTS: Education, household economic well being, and urban-rural residence
      showed statistically significant gross effects on old age mortality. Education
      influenced mortality directly and indirectly. Household economic well being and
      urbanicity exerted indirect effects on mortality through mediating variables such
      as stress, social relations, and baseline health status. The mechanism through
      which education affected mortality differed between men and women, but SES
      differentials in mortality did not interact with age. DISCUSSION: SES
      differentials in old age mortality may be extended to a developing nation such as
      China. The observed gender by SES interaction effect on old age mortality has
      important implications for intervention. In particular. improving education among
      women in underdeveloped areas must remain a high priority, for policy makers in
      efforts to extend the life expectancy of women.

PMID- 11584886
TI  - Dimensions of care for dementia sufferers in long-term care institutions: are
      they related to outcomes?
AB  - OBJECTIVES: This study empirically examined whether dimensions of care cluster in
      special care units (SCUs) compared with non-SCUs. The relationship between SCU
      status plus separate measures of the dimensions of care and outcomes for dementia
      sufferers was then investigated. METHODS: Data were drawn from the Intermediate
      Care Facility Project. The sample (N = 510) included residents with dementia,
      aged 65 and older, in intermediate care facilities throughout the province of
      British Columbia. Canada. Longitudinal data included 6 outcomes: cognitive
      function, behavioral problems of agitation and social skills, physical
      functioning, and quality of life measured through affect and expressive language
      skills. Separate multiple linear regression equations were estimated, relating
      each of these outcomes to 5 dimensions of care: preadmission and admission
      procedures. staff training and education, nonuse of physical and chemical
      restraints, flexible care routines and resident-relevant activities, and the
      environment. RESULTS: The results showed there is virtually no clustering of
      dimensions along SCU/non-SCU lines. Neither SCU status nor the individual
      dimensions were highly predictive of outcomes. Residents' affect at t1 emerged as
      a characteristic that was significantly correlated with other outcomes.
      DISCUSSION: This Canadian research can be added to the few but growing number of
      rigorous studies that suggest SCUs are not homogeneous and do not necessarily
      provide better care than non-SCUs. Moreover, it raises questions about the
      benefits of "best practice" dimensions of care, regardless of SCU status.

PMID- 11584887
TI  - Changes in home care use by disabled elderly persons: 1982-1994.
AB  - OBJECTIVES: The use of, and changes in the use of. formal (paid) and informal
      care by elderly persons who are chronically disabled and living in the community
      was studied. METHODS: Estimates were made of the sources and volume of home care
      use for persons reporting chronic disability in the 1982, 1989, and 1994 National
      Long Term Care Surveys. Comparisons were made across disability intensity, survey
      data, and age. RESULTS: The analyses showed changes over time in the sources of
      home care services. Generally, the combined use of both paid and informal home
      health care increased, whereas the use of either source of care alone decreased.
      The amount spent on formal care increased with disability level and age.
      DISCUSSION: Use of formal sources of care by community disabled elderly residents
      increased, likely because of changes in the Medicare home health care benefits in
      1989. Increased use of home health care was associated with the concurrent use of
      informal care.

PMID- 11584888
TI  - Rise in inappropriate breast cancer treatment.

PMID- 11584889
TI  - 'No benefit' from mammography.

PMID- 11584890
TI  - Doubts raised over tamoxifen as preventive agent.

PMID- 11584891
TI  - National cancer plan launched.

PMID- 11584892
TI  - Ex vivo pediatric brain tumors express Fas (CD95) and FasL (CD95L) and are
      resistant to apoptosis induction.
AB  - Fas (APO-1/CD95/TNFRSF6) is a member of the tumor necrosis/nerve growth factor
      receptor family that signals apoptotic cell death in sensitive cells. Expression
      of Fas and its agonistic ligand (FasL/TNFSF6) was investigated in ex vivo
      pediatric brain tumor specimens of various histologic types. Fas expression was
      identified in all of the 18 tumors analyzed by flow cytometry and
      immunohistochemistry. FasL expression was identified in most of the 13 tumors
      analyzed by both Western analysis and immunohistochemistry. Nine of these tumor
      specimens were treated with either the agonistic anti-Fas antibody (APO-1) in
      combination with protein A or FasL in short-term cytotoxicity assays. Sensitivity
      to apoptosis induced by the topoisomerase II inhibitor, etoposide, was also
      assessed. Despite the presence of Fas, all the specimens analyzed demonstrated a
      high degree of resistance to Fas-mediated apoptosis. These 9 specimens also
      showed a high degree of resistance to etoposide. Only 2 of the 9 specimens were
      susceptible to etoposide-induced cell death, whereas only 3 were sensitive to Fas
      mediated apoptosis. One brain tumor was sensitive to both Fas ligation and
      etoposide treatment. This contrasted with the high degree of susceptibility to
      both etoposide- and Fas-induced apoptosis observed in the reference Jurkat cell
      line. The results suggest that Fas expression may be a general feature of tumors
      of the CNS and that a significant degree of resistance to Fas-mediated apoptosis
      may exist in ex vivo pediatric brain tumor specimens.

PMID- 11584893
TI  - Levels of N7-(2-hydroxyethyl)guanine as a molecular dosimeter of drug delivery to
      human brain tumors.
AB  - The level of N7-(2-hydroxyethyl)guanine (N7-HOEtG), one of the DNA alkylation
      products formed by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment, was
      measured in human brain tumor samples by high performance liquid chromatography
      with electrochemical detection. The tumors from 6 recurrent chemotherapy-naive
      patients with recurrent glioblastoma multiforme were analyzed as controls. The
      mean level of N7-HOEtG in DNA of these specimens was 0.42 pmol/mg DNA. Samples
      were also obtained from a patient with a recurrent glioblastoma multiforme after
      direct intratumoral therapy with BCNU in ethanol (DTI-015). The levels of N7
      HOEtG in the samples distal, medial, and adjacent to the site of injection were
      0.8, 2.6, and 369.5 pmol/mg DNA, respectively. Comparison of the level of N7
      HOEtG detected in the distal sample after injection with BCNU in ethanol with the
      mean level of the untreated samples indicated that it was not sufficiently
      different to be ruled out as a chance occurrence. Comparison of the levels of N7
      HOEtG in the medial and adjacent brain tumor samples with the mean level of the
      control samples showed values that were approximately 6- and 879-fold higher.
      These results demonstrate that intratumoral administration of BCNU in ethanol
      produces significant levels of DNA alkylation and suggest that DNA adduct
      measurements provide a unique molecular dosimeter to evaluate delivery of
      alkylating agents to brain tumors.

PMID- 11584894
TI  - Phase I study of Gliadel wafers plus temozolomide in adults with recurrent
      supratentorial high-grade gliomas.
AB  - Both Gliadel wafers [1,3-bis(2-chloroethyl)-1-nitrosourea] and temozolomide
      (TEMO) have been shown in independent studies to prolong survival of patients
      with recurrent malignant glioma following surgery and radiotherapy. On the basis
      of preclinical evidence of synergism between Gliadel wafers and TEMO, a phase I
      study was designed to evaluate the toxicity of combining these 2 agents in the
      treatment of patients with recurrent supratentorial malignant glioma. All
      patients had surgical resection of the tumor at relapse, and up to 8 Gliadel
      (3.85%) wafers were placed in the surgical cavity following resection. Two weeks
      after surgery, TEMO was given orally daily for 5 days. Cohorts of 3 patients
      received TEMO at daily doses of 100 mg/m2, 150 mg/m2, and 200 mg/m2,
      respectively. Patients were assessed for toxicity 4 weeks after start of the
      first course of TEMO. Contrast-enhanced MRI of the brain was used to assesstumor
      response after the first cycle of TEMO. Patients with stable disease or response
      after the first cycle of TEMO were allowed to continue treatment at the same dose
      every 4 weeks for 12 cycles or until disease progression or unacceptable
      toxicity. Ten patients with a median age of 47 years (range, 22-66 years) were
      enrolled in this study. There were 7 patients with glioblastoma multiforme and 3
      patients with anaplastic astrocytoma. Three patients were treated with TEMO at
      the first dose level of 100 mg/m2, 4 at the second dose level of 150 mg/m2, and 3
      at the third dose level of 200 mg/m2. The 10 patients received a median of 3
      cycles (range, 1-12 cycles) of TEMO following placement of Gliadel wafers. The
      treatment was well tolerated, with only 1 patient suffering grade III
      thrombocytopenia at the highest dose level. Two patients at each dose level had
      no evidence of disease progression after treatment. Four patients suffered
      progressive disease on therapy. Our study demonstrates that TEMO can be given
      safely after placement of Gliadel (3.85%) wafers. The recommended dosage for TEMO
      for a phase II study of this combination is 200 mg/m2 per day for 5 days.

PMID- 11584895
TI  - Carboplatin chemotherapy for progressive intramedullary spinal cord low-grade
      gliomas in children: three case studies and a review of the literature.

PMID- 11584896
TI  - Immunotherapy Task Force for malignant brain tumors. April 21, 2001, Toronto,
      Ontario.

PMID- 11584897
TI  - Elevated thyroid hormone levels with normal or raised thyroid-stimulating
      hormone: a diagnostic and therapeutic dilemma.

PMID- 11584898
TI  - Small molecule: large hopes.

PMID- 11584899
TI  - Cerebral venous sinus thrombosis: a diagnostic challenge.
AB  - BACKGROUND: Cerebral venous sinus thrombosis (CVT) is a potentially serious but
      treatable disorder that has been underdiagnosed in the past. Delay in diagnosis
      and treatment of this disorder has resulted in the death of one of our patients.
      AIM: To review the local experience with CVT in order to identify factors that
      may allow diagnosis and appropriate treatment decisions to be made more readily
      in the future. METHODS: A retrospective review of all cases of CVT diagnosed or
      treated at Auckland Hospital between 1990 and 1999. RESULTS: Twenty-five cases of
      CVT were identified. The number of cases diagnosed increased from less than one
      per year in 1990-94 to eight in 1999. Clinical signs at presentation included
      headache (96%), focal neurological deficits (60%), seizures (40%) and
      papilloedema (43%). Delayed diagnosis after admission to hospital occurred in two
      young women presenting with neurological symptoms during pregnancy or puerperium,
      in two cases in whom focal symptoms were not explained by negative computed
      tomography and in five cases presenting with intracerebral haemorrhage. Twenty
      patients received anticoagulant therapy and their condition remained stable or
      improved after treatment. CONCLUSIONS: The diagnosis of CVT should be considered
      in women with any neurological symptoms during pregnancy or puerperium and in all
      cases of unexplained intracerebral haemorrhage. CVT should also be considered in
      cases of recent onset and progressive headache, particularly when associated with
      focal neurological symptoms or signs, seizures or papilloedema. Magnetic
      resonance imaging with magnetic resonance venography is the investigation of
      choice. Anticoagulation with heparin remains the mainstay of treatment, even in
      the presence of intracerebral haemorrhage.

PMID- 11584900
TI  - Underuse of beta-blockers following myocardial infarction: a tale of two cities.
AB  - AIMS: To measure factors associated with underuse of beta-blocker therapy after
      myocardial infarction (MI). METHODS: The Newcastle and Perth collaborating
      centres of the World Health Organization (WHO) MONICA project (to MONItor trends
      and determinants of Cardiovascular disease) systematically evaluated all patients
      admitted to hospital in their respective regions with possible MI. A total of
      1766 patients in Newcastle and 4,503 patients in Perth, discharged from hospital
      after confirmed MI from 1985 to 1993, were studied. Rates of beta-blocker use
      before and after hospital discharge were evaluated and correlates of beta-blocker
      use determined. RESULTS: Beta-blocker use was similar in Newcastle and Perth
      before MI (21% of patients in each centre). During hospital admission, beta
      blocker therapy was initiated nearly twice as frequently in Perth compared with
      Newcastle (66 vs 36%, respectively) and more patients were discharged from
      hospital on beta-blockers in Perth (68%) than in Newcastle (45%). The main
      factors associated with underuse of beta-blockers in multivariate analysis were
      geographical centre (odds ratio (OR) for Newcastle compared with Perth 0.3; 95%
      confidence interval (CI) 0.3-0.3), a history of previous MI (OR 0.6, 95% CI 0.5
      0.7), admission to hospital in earlier years (OR 0.4, 95% CI 0.3-0.4 for years
      1985-87 compared with years 1991-93), diabetes (OR 0.6, 95% CI 0.5-0.8) and the
      concomitant use of diuretics (OR 0.5, 95% CI 0.4-0.6) and calcium antagonists (OR
      0.6, 95% CI 0.5-0.8). CONCLUSIONS: Underuse of beta-blockers after MI was
      strongly related to hospital prescribing patterns and not to community use of
      beta-blockers. Underuse occurred in patients with diabetes and in patients with
      left ventricular dysfunction, patients who stand to benefit most from beta
      blocker use following MI.

PMID- 11584901
TI  - Psychological impact of genetic counselling and testing in women previously
      diagnosed with breast cancer.
AB  - BACKGROUND: The recent discovery of susceptibility genes relating to breast
      cancer, BRCA1 and BRCA2, now allows women with breast cancer and a family history
      of breast/ovarian cancer to undergo genetic testing to identify a causative germ
      line mutation. The present study assessed the psychological status over time of
      women affected by breast cancer requesting genetic testing (cases; n = 32)
      compared with matched controls (n = 28). METHODS: Subjects were recruited through
      two Sydney-based hospitals. Data were collected via questionnaire and telephone
      interview at baseline, and 2 weeks and 3-6 months following counselling. RESULTS:
      Genetic test results were not received by the subjects within the study period.
      Cases showed a greater increase in knowledge of cancer genetics following
      counselling compared with controls, and this was maintained over time.
      Psychological symptoms remained stable over the study period and there were no
      differences between groups. CONCLUSIONS: Increased knowledge following genetic
      counselling was not accompanied by an increase in anxiety or depression. Further
      assessment will be required in the long term to determine the psychological
      impact of receiving a genetic test result.

PMID- 11584902
TI  - Retrospective review of febrile neutropenia in the Royal Darwin Hospital, 1994
      99.
AB  - BACKGROUND: Febrile neutropenia is a life-threatening complication of cytotoxic
      chemotherapy. Empirical antibiotic treatment should be based on predominant
      pathogens and epidemiological characteristics of the treated community. The aim
      of the present study was to review cases of febrile neutropenia at the Royal
      Darwin Hospital (RDH) in order to assess the appropriateness of empirical
      antibiotic therapy. METHODS: A retrospective review of cases of febrile
      neutropenia secondary to malignancy or chemotherapy occurring at the RDH over the
      period 1994-99. In order to compare infections in this group with those in the
      wider hospital community, all positive blood cultures in the medical and
      intensive care units were reviewed for the same time period. RESULTS: Thirty-six
      episodes of febrile neutropenia were reviewed. Staphylococcus aureus
      (predominantly methicillin resistant), Pseudomonas aeruginosa and Escherichia
      coli were the most common organisms identified. Nine patients died of their
      infection, four with methicillin-resistant S. aureus bacteraemia. S. aureus, E.
      coli, Streptococcus pneumoniae and Burkholderia pseudomallei (melioid) were the
      most frequently isolated organisms from blood cultures taken in the medical and
      intensive care units. CONCLUSIONS: Gram-positive organisms are the predominant
      pathogens in febrile neutropenic episodes at the RDH. Standard empirical therapy
      with an extended-spectrum penicillin and an aminoglycoside remains appropriate,
      with the addition of vancomycin when clinical status fails to improve. When
      practising in the Top End, particular consideration should be given to skin
      integrity and scabies and testing for Strongyloides in Aboriginal patients.

PMID- 11584903
TI  - The relationship between law and ethics in medicine.

PMID- 11584904
TI  - The Clinical Support Systems Program concept: what is it and where did it come
      from?

PMID- 11584905
TI  - Human immunodeficiency virus-hepatitis C coinfection: swapping new problems for
      newer ones.
AB  - Recent successes in HIV therapy have uncovered other health problems for HIV
      infected individuals. Hepatitis C has become an especially significant problem,
      partly due to its faster progression in an immunocompromised setting. In
      addition, the higher viral loads in coinfected patients likely result in more
      efficient perinatal and perhaps even sexual transmission. Therapy has largely
      been neglected, despite data suggesting its efficacy in HIV-HCV coinfected
      patients. Studies of combination interferon and ribavirin studies are lacking,
      although underway. A major concern is the potential inactivation of certain
      thymidine analogues by ribavirin. Some antiretroviral therapies, such as
      ritonavir, indinavir and nevirapine, may enhance liver toxicity in coinfected
      patients and should be avoided if possible. The role of chronic low-grade liver
      function abnormalities remains uncertain and requires further investigation.

PMID- 11584906
TI  - Origins and development of geriatric medicine in Australia.
AB  - After a tentative beginning 50 years ago, geriatric medicine has become an
      accepted part of medical practice in Australia. It includes the rehabilitation of
      elderly people, general aspects of aged care in the community, undergraduate and
      postgraduate education and research.

PMID- 11584907
TI  - Poetry and medicine: healing for the healer. A call for a literary supplement.

PMID- 11584908
TI  - Asymptomatic thyrotropin-secreting pituitary microadenoma.

PMID- 11584909
TI  - Chronically elevated thyroid-stimulating hormone: resistance to thyroid hormone.

PMID- 11584910
TI  - Unusual combination of positive IgG autoantibodies in acute Q-fever infection.

PMID- 11584911
TI  - Chlorhexidine anaphylaxis: a case report and review of the literature.

PMID- 11584912
TI  - Acute liver failure in a patient with sickle cell/beta+ thalassaemia.

PMID- 11584914
TI  - Finding your way in the dark: the retrosplenial cortex contributes to spatial
      memory and navigation without visual cues.
AB  - Path integration is presumed to rely on self-motion cues to identify locations in
      space and is subject to cumulative error. The authors tested the hypothesis that
      rats use memory to reduce such errors and that the retrosplenial cortex
      contributes to this process. Rats were trained for 1 week to hoard food in an
      arena after beginning a trial from a fixed starting location; probe trials were
      then conducted in which they began a trial from a novel place in light or
      darkness. After control injections, rats searched around the training location,
      showing normal spatial memory. Inactivation of the retrosplenial cortex disrupted
      this search preference. To assess accuracy during navigation, rats were then
      trained to perform multiple trials daily, with a fixed or a different starting
      location in light or darkness. Retrosplenial cortex inactivation impaired
      accuracy in darkness. The retrosplenial cortex may provide mnemonic information,
      which decreases errors when navigating in the dark.

PMID- 11584913
TI  - Cortisol differentially affects memory in young and elderly men.
AB  - Nine young and 11 elderly men participated in this placebo-controlled, double
      blind, crossover study (0.5 mg/kg cortisol or intravenous placebo). Participants
      learned a word list before cortisol administration, and delayed recall was then
      tested. A 2nd word list was learned and recalled after drug administration. In
      addition, the Paragraph Recall Test and tests measuring working memory (Digit
      Span), attention (timed cancellation), and response inhibition (Stroop Color and
      Word Test) were administered at 2 time points after drug administration. Cortisol
      reduced recall from the word list learned before treatment in both groups but did
      not influence recall of the list learned after treatment. In contrast, Digit Span
      performance was decreased by cortisol in young but not elderly participants. The
      possibility that differential age-associated brain changes might underlie the
      present results is discussed.

PMID- 11584915
TI  - Posttraining lesions of the medial prefrontal cortex impair performance of
      Pavlovian eyeblink conditioning but have no effect on concomitant heart rate
      changes in rabbits (Oryctolagus cuniculus).
AB  - The medial prefrontal cortex (mPFC) plays a critical role in conditioned
      autonomic adjustments but is not involved in classically conditioned somatomotor
      responses unless the training conditions include reversal or trace conditioning.
      The studies showing these effects have all used pretraining lesions. The present
      study assessed the effects of posttraining lesions on eyeblink (EB) and heart
      rate (HR) conditioned responses (CRs) in both delay and trace conditioning
      paradigms in the rabbit (Oryctolagus cuniculus). Posttraining lesions lowered the
      percentage of EB CRs during retesting compared with pretesting levels for both
      delay and trace conditioning. Control lesions and pretraining lesions produced no
      significant effects during retesting. Posttraining lesions had no effect on the
      HR CR. These findings suggest that a critical mechanism in the mPFC is involved
      in retrieval of information during EB conditioning but that the mPFC integration
      of autonomic and somatomotor processes is not critical to this retrieval process.

PMID- 11584916
TI  - Conditioning-specific reflex modification of the rabbit (Oryctolagus cuniculus)
      nictitating membrane response: generality and nature of the phenomenon.
AB  - Conditioning-specific reflex modification (CRM) occurs when classical
      conditioning modifies responding to an unconditioned stimulus in the absence of a
      conditioned stimulus. This form of reflex modification suggests that learning
      modifies the unconditioned reflex pathway. Rabbit (Oryctolagus cuniculus)
      nictitating membrane responses to 5 intensities and 3 durations of airpuff (AP)
      or periorbital electrical stimulation (ES) were monitored before and after
      conditioning. AP tests detected strong CRM after conditioning with ES and modest
      levels of CRM after conditioning with AP. After conditioning with AP, ES tests
      failed to detect CRM. After conditioning with a stronger AP, CRM was again
      detected by AP tests. CRM is a general phenomenon but is more readily detected
      after training with a relatively aversive stimulus; thus, it may be a function of
      level of arousal.

PMID- 11584917
TI  - Rats with hippocampal lesions can learn a place response, but how long can they
      retain it?
AB  - Previous research has shown that electrolytic hippocampal lesions do not affect
      the acquisition of a place response if a special training procedure is used.
      However, 24 days later, the hippocampal rats manifest a profound deficit in the
      retention of the spatial information (J. M. J. Ramos, 2000). The goal of the
      present study was, therefore, to investigate how long the hippocampal rats can
      retain a place response. Results showed that, 3 days after the end of the
      training, lesioned rats remembered as well as the control rats, but this was no
      longer true 6 or 12 days after the training. This retention deficit was not
      observed when the spatial information was acquired by means of a guidance
      strategy. These results suggest that, when a special training procedure is used,
      the hippocampus is not necessary for the learning of a place task but is required
      for the formation of long-term spatial memory.

PMID- 11584918
TI  - Effect of age on object exploration, habituation, and response to spatial and
      nonspatial change.
AB  - To measure their ability to detect novel arrangements in a given environment,
      young (6 months old) and senescent (22-24 months old) male F344 rats were
      repeatedly exposed to a given spatial configuration of objects contained in an
      open field. After the rats were habituated to the novel environment (1 trial with
      no objects, followed by 3 trials with 5 salient objects), the spatial arrangement
      of the objects was modified (2 trials), and object novelty was tested (2 trials)
      by substituting a familiar object with a new one at the same location (nonspatial
      change). The results indicated that the senescent rats explored old objects less
      than young rats, particularly on Trial 2. On the 1st trial with displaced objects
      (Trial 5), the senescent rats explored the displaced objects less than the young
      rats. However, when a new object was placed in the field (Trials 7-8), there were
      no age differences in new object exploration. These results suggest that
      senescent rats have decrements in the ability to build spatial representations of
      the environment and to use this information to detect such changes, even though
      object recognition is not impaired with age.

PMID- 11584919
TI  - Conditioning of ictal and interictal behaviors in rats by amygdala kindling:
      context as the conditional stimulus.
AB  - The authors showed that conditional effects of the stimulation environment
      modulate both the ictal and interictal behaviors of rats subjected to amygdala
      kindling. Rats received 53 stimulations to the left basolateral amygdala in 1
      conditional stimulus (CS) context (CS+) and 53 sham stimulations (the stimulation
      lead was attached but no current was delivered) in another context (CS-),
      quasirandomly over 54 days. Three kinds of conditional effects were observed.
      First, after several stimulations, less ambulatory activity, more freezing, and
      less rearing reliably occurred in the CS+ context than in the CS-context. Second,
      after 45 stimulations, all of the rats chose the CS- context over the CS+ context
      in a conditioned place preference test. Third, when the rats were finally
      stimulated in the CS- context, their motor seizures were less severe: Latencies
      were longer, motor seizures were shorter, convulsive patterns were of a lower
      class, and there were fewer falls.

PMID- 11584920
TI  - Functional recovery of taste sensitivity to sodium chloride depends on
      regeneration of the chorda tympani nerve after transection in the rat.
AB  - Chorda tympani nerve (CT) transection (CTX) raises sodium chloride (NaCl) taste
      detection threshold, but the effect of CT regeneration on NaCl threshold is
      unknown. This experiment examined whether CT regeneration supports normal NaCl
      threshold in the rat. Thresholds were measured with a 2-lever operant procedure.
      Thresholds increased more than 1 order of magnitude after CTX regardless of
      recovery period length. Postsurgical thresholds in rats with regenerated CTs did
      not differ from presurgical values. Stimulus adulteration with amiloride raised
      thresholds in rats with intact or regenerated CTs by about 1 order of magnitude
      but did not raise thresholds beyond postsurgical levels in rats with transected
      CTs. Thus, the regenerated CT supports normal NaCl threshold, which is raised by
      amiloride. Because thresholds remained elevated 62 days after CTX when
      regeneration was prevented, compensatory processes alone cannot support normal
      NaCl threshold.

PMID- 11584921
TI  - Conditioned reinstatement of drug-seeking behavior with a discrete compound
      stimulus classically conditioned with intravenous cocaine.
AB  - The present study investigated the ability of a light and tone (LT) compound
      stimulus paired with cocaine infusions to reinstate cocaine-seeking behavior.
      Rats were trained to self-administer cocaine in the presence or absence of the LT
      during daily 3-hr sessions (maintenance). During Maintenance Days 5 and 10, rats
      underwent classical conditioning, whereby passive cocaine infusions were paired
      with either short-delayed, random, or no presentations of an LT. After extinction
      sessions, rats underwent test sessions in which the LT was presented in a
      noncontingent or response-contingent manner to measure conditioned cocaine
      seeking behavior. The results demonstrated that response-contingent LT
      presentations significantly increased cocaine-seeking behavior and that the LT
      trained in a classical conditioning format transferred to an operant secondary
      reinforcer.

PMID- 11584922
TI  - Characterization of the role of medial prefrontal cortex dopamine receptors in
      cocaine-induced locomotor activity.
AB  - Medial prefrontal cortex (mPFC) dopamine (DA) modulates the motor-stimulant
      response to cocaine. The present study examined the specific mPFC DA receptor
      subtypes that mediate this behavioral response. Intra-mPFC injection of the DA D2
      like receptor agonist quinpirole blocked cocaine-induced motor activity, an
      effect that was prevented by coadministration of the D2 receptor antagonist
      sulpiride. Intra-mPFC injection of the selective D4 receptor agonist PD 168,077
      or the selective D1 receptor agonist SKF 81297 did not alter the motor-stimulant
      response to cocaine. Finally, it was found that an intermediate dose of
      quinpirole, which only attenuated cocaine-induced motor activity, was not altered
      by SKF 81297 coadministration, suggesting a lack of synergy between mPFC D1 and
      D2 receptors. These results suggest that D2 receptor mechanisms in the mPFC are
      at least partly responsible for mediating the acute motor-stimulant effects of
      cocaine.

PMID- 11584923
TI  - Day-by-day maturation of the long-term expression of cocaine sensitization
      acquired before weaning in the rat.
AB  - This study aimed to identify the ontogenetic period during which long-term
      expression of behavioral sensitization to cocaine begins to emerge. Rat pups aged
      4, 8, 12, or 16 days received a pretreatment of 4 daily injections of 15 mg/kg sc
      cocaine paired with the test chamber for 45 min. Pups were then tested for
      sensitization in that context after abstinence intervals ranging from 2 to 10
      days. On test days, pups were videotaped, and their behavior was scored later.
      Sensitization was detected after intervals of 2, 4, 5, or 9 days in pups aged 4
      7, 8-11, 12-15, or 16-19 days during pretreatment, respectively. These results
      suggest that the mechanisms for long-term retention of sensitization mature
      incrementally in the rat, starting to emerge gradually after the 1st week of age,
      whereas those relevant to short-term retention and initiation of sensitization
      are present earlier.

PMID- 11584924
TI  - Increased maternal corticosterone levels in rats: effects on brain 5-HT1A
      receptors and behavioral coping with stress in adult offspring.
AB  - This study examined the consequences of elevated corticosterone levels in
      lactating rats on their offspring's serotonergic 5-hydroxytryptamine (5-HT)1A
      receptor system and behavioral coping with stress. The mothers received normal
      drinking water or water with corticosterone, which, via the milk, enters the
      circulation and brains of the pups. In adulthood, the corticosterone-nursed
      offspring showed a consistently more passive way of coping with environmental
      challenges. However, they did not seem to be more anxious. Autoradiographic
      analysis of the 5-HT1A receptor system revealed a decrease in the adult 5-HT1A
      receptor binding in the hippocampal CA1 region. The results support the
      hypothesis that differences in behavioral coping with stress by adult rats are
      associated with differences in the serotonergic system. At the same time, it
      suggests that adult coping and its neuronal substrates are not solely determined
      by genes but depend on subtle developmental factors as well.

PMID- 11584925
TI  - Progesterone and 3alpha,5alpha-THP enhance sexual receptivity in mice.
AB  - Progesterone (P) and its metabolites' effects on sexual receptivity (lordosis) of
      mice was examined. P dosages that produced normal circulating concentrations of P
      and 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) enhanced lordosis of
      ovariectomized, sexually experienced C57BL/6J (C57), +/+ C57BL/6Jx129SvEv
      (C57x129), and -/- C57BL/6Jx129SvEv (PRKO) mice. Only C57 and C57x129 mice had
      increases in progestin receptor (PR)-immunoreactivity (PR-IR) in the
      hypothalamus. RU38486, a PR antagonist, attenuated lordosis of C57 and C57x129,
      but not PRKO, mice; epostane, a progestin biosynthesis inhibitor, reduced plasma
      progestins; and finasteride, a P metabolism inhibitor, reduced plasma
      3alpha,5alpha-THP and attenuated lordosis of all mice. For sexually naive mice,
      greater lordosis on initial sexual experience corresponded to greater
      concentrations of plasma and central progestins and increased central binding of
      a GABAA agonist, muscimol, compared with that seen in mice with lower lordosis on
      initial mating. Thus, P-facilitated receptivity in mice involves P and
      3alpha,5alpha-THP and their actions at PRs and GABAA receptors.

PMID- 11584926
TI  - Behavioral characterization of dopamine D5 receptor null mutant mice.
AB  - To study behavioral functions of the D5 subtype, mice were generated with null
      mutations in the D5 gene. This 1st behavioral characterization of D5 null mutant
      mice (D5-/-) indicated normal general health, sensory abilities, and neurological
      reflexes. Under basal conditions, D5-/- mice were generally normal on locomotor
      activity, the rotarod test, acoustic startle response, prepulse inhibition,
      elevated plus-maze, light <--> dark exploration, Morris water maze, and cued and
      contextual fear conditioning. In the Porsolt forced swim test for antidepressant
      activity, male D5-/- mice showed lower levels of immobility. D5-/- mice showed
      some evidence of reduced responses to the hyperactivity-inducing effects of the
      D1/D5 receptor agonist SKF 81297. The ability of SKF 81297 to disrupt acoustic
      startle and prepulse inhibition appeared to be attenuated in D5-/- mice. These
      results suggest that the D5 receptor is not essential for many dopamine-mediated
      behaviors but may contribute to the pharmacological activation of dopaminergic
      pathways relevant to exploratory locomotion, startle, and prepulse inhibition.

PMID- 11584927
TI  - Performance of heterozygous brain-derived neurotrophic factor knockout mice on
      behavioral analogues of anxiety, nociception, and depression.
AB  - Evidence suggests that brain-derived neurotrophic factor (BDNF) may be important
      in the pathophysiology of depression, in addition to its role as a neurotrophic
      factor for sensory neurons. The authors conducted a series of experiments
      examining the behavioral profile of BDNF heterozygous knockout and wild-type
      mice. The heterozygous and wild-type mice did not differ on measures of activity,
      exploration, or hedonic sensitivity, or in the forced swim test. When assessed in
      the learned helplessness paradigm, heterozygous mice were slower to escape after
      training than were wild-type mice (p = .02). This effect may be accounted for by
      the fact that these mice demonstrate a reduced sensitivity to centrally mediated
      pain, apparent on the hot plate and Formalin injection tests of nociception.
      Overall, heterozygous mice were not more likely to display anxious or depressive
      like behaviors and, consequently, may not constitute a murine model of genetic
      vulnerability to mood and anxiety disorders.

PMID- 11584928
TI  - Inhibitory learning tests of conditioned stimulus associability in rats with
      lesions of the amygdala central nucleus.
AB  - Normal rats showed faster inhibitory learning about a light conditioned stimulus
      (CS) if it had previously been an inconsistent predictor of a tone CS than if it
      had been a consistent predictor of the tone. In contrast, the inhibitory learning
      of rats with ibotenic acid lesions of the amygdala central nucleus (CN) was
      unaffected by the prior predictive value of the light. These results support
      claims that the CN is critical to surprise-induced enhancement of attentional
      processing of CSs.

PMID- 11584929
TI  - Neuroanatomical localization of the motor hand area with magnetic resonance
      imaging: the left hemisphere is larger in great apes.
AB  - Magnetic resonance images of the brain were obtained from 2 gorillas (Gorilla
      gorilla gorilla), 4 orangutans (Pongo pygmaeus), 14 chimpanzees (Pan
      troglodytes), and 4 bonobos (Pan paniscus). The region on the motor cortex of
      humans identified as responsible for motor skill of the hand (the "knob") was
      identified in this sample on consecutive 1-mm axial scans. The shape of the knob
      area was traced on each scan from both hemispheres, and the area from all scans
      was summed to calculate the knob volume. The width of the knob was also measured
      and correlated highly with knob volume. A significant population-level leftward
      asymmetry in the volume and width of the knob was revealed (p < .05). Species
      differences in knob asymmetry and overall volume were not significant, but the
      variability in overall volume between species was substantial. Selection for the
      evolution of a neuroanatomical representation of the hand in primates and an
      evolutionary trend toward population-level right handedness are discussed.

PMID- 11584930
TI  - The role of ventral and orbital prefrontal cortex in conditional visuomotor
      learning and strategy use in rhesus monkeys (Macaca mulatta).
AB  - Four rhesus monkeys (Macaca mulatta) were trained to learn novel sets of
      visuomotor associations in 50 trials or less, within single test sessions. After
      bilateral ablation of the orbital and ventral prefrontal cortex, the monkeys lost
      the ability to learn these associations within a session, although they could
      learn them when given several daily sessions. Thus, relatively slow, across
      session visuomotor learning depends on neither the ventral nor orbital prefrontal
      cortex, but rapid, within-session learning does. The ablations also eliminated at
      least 2 response strategies, repeat-stay and lose-shift, which might account, in
      part, for the deficit in rapid learning. The deficit is unlikely to result from a
      failure of visual discriminative ability or working memory: The monkeys could
      discriminate similar stimulus material within a session, and reducing the working
      memory load did not improve within-session learning.

PMID- 11584931
TI  - The amygdala's role in long-term declarative memory for gist and detail.
AB  - In humans, the emotional nature of stimuli appears to have a complex influence on
      long-term declarative memory for those stimuli: Whereas emotion enhances memory
      for gist, it may suppress memory for detail. On the basis of prior studies, the
      authors hypothesized that the amygdala helps mediate the above 2 effects. Long
      term memory for gist and for visual detail of aversive and neutral scenes was
      assessed in 20 subjects with unilateral amygdala damage and 1 rare subject with
      bilateral amygdala damage. Comparisons with 2 control groups (15 brain-damaged
      and 47 healthy) provided evidence that bilateral, but not unilateral, damage to
      the amygdala results in poorer memory for gist but superior memory for visual
      details. The pattern of findings provides preliminary support for the idea that
      the amygdala may help filter the encoding of relevant information from stimuli
      that signal threat or danger.

PMID- 11584932
TI  - Probabilistic contingency learning with limbic or prefrontal damage.
AB  - A fundamental capacity of the human brain is to learn relations (contingencies)
      between environmental stimuli and the consequences of their occurrence. Some
      contingencies are probabilistic; that is, they predict an event in some
      situations but not in all. Animal studies suggest that damage to limbic
      structures or the prefrontal cortex may disturb probabilistic learning. The
      authors studied the learning of probabilistic contingencies in amnesic patients
      with limbic lesions, patients with prefrontal cortex damage, and healthy
      controls. Across 120 trials, participants learned contingent relations between
      spatial sequences and a button press. Amnesic patients had learning comparable to
      that of control subjects but failed to indicate what they had learned. Across the
      last 60 trials, amnesic patients and control subjects learned to avoid a
      noncontingent choice better than frontal patients. These results indicate that
      probabilistic learning does not depend on the brain structures supporting
      declarative memory.

PMID- 11584933
TI  - Visceral leishmaniasis: can we dream its eradication?

PMID- 11584934
TI  - A randomized clinical trial of low dosage combination of pentamidine and
      allopurinol in the treatment of antimony unresponsive cases of visceral
      leishmaniasis.
AB  - OBJECTIVES: A randomized clinical trial of low dosage combination of pentamidine
      and allopurinol was carried out with objectives to assess the efficacy and
      toxicity as compared to full dosage of pentamidine in antimony unresponsive
      visceral leishmaniasis (VL) patients. METHODS: Using a randomized control
      clinical trial, a total of 158 antimony unresponsive patients of VL were randomly
      allocated into two treatment groups. Patients in one group (n=80) received half
      the dosage of pentamidine i.e. 2 mg/kg body weight by IM route on alternate day
      and allopurinol in dose of 15 mg/kg body weight in three divided dosages for 30
      days; patients in the second group (n=78) received pentamidine in dose of 4 mg/kg
      body weight by IM route on alternate day for 15 injections in 30 days. The
      efficacy and safety of the two regimens were compared. RESULTS: Apparent cure
      i.e. clinical and pathological cure at the end of therapy, in 78 (97.5%) and 67
      (86%), and ultimate cure i.e. clinical and parasitological cure at the end of
      follow-up of six months, in 73 (91.25%) and 58 (74.35%) patients was observed in
      the combination regimen and single regimen group respectively. The difference of
      the ultimate cure between two groups of the patients was statistically
      significant (p < 0.01). In single regimen group, 11 (14%) patients showed primary
      unresponsiveness (with no response during treatment) and nine (13%) relapse
      (after six months of follow-up) respectively, where as in combination regimen
      group, two (2.5%) patients showed primary unresponsiveness and five (6.4%)
      relapse respectively. By the end of the treatment, the incidence of injection
      related toxicity, such as rigor and fever, was same in both groups. No
      hyperglycemia was observed in combination therapy probably due to reduced dose of
      pentamidine and three patients in single regimen developed hyperglycemia and one
      of them developed irreversible hyperglycemia. CONCLUSIONS: The study showed that
      the combination of pentamidine (half dose) and allopurinol is more effective in
      achieving ultimate cure with an added advantage of reduced toxicity in
      unresponsive cases as compared to full pentamidine dose.

PMID- 11584935
TI  - Left atrial and pulmonary artery wedge pressure monitoring during balloon mitral
      valvuloplasty.
AB  - OBJECTIVE: We tested the accuracy of pulmonary artery wedge (PAW) pressure as a
      guide to the degree of pulmonary venous hypertension. METHODS: Left atrial (LA)
      pressure and PAW pressure were analysed before and after balloon mitral
      valvuloplasty (BMV) in patients with rheumatic mitral stenosis. RESULTS:
      Correlations between LA and PAW pressures for a wave, v wave and mean pressure
      were excellent before BMV (r=0.96, r=0.97 and r=0.99 respectively) and after BMV
      (r=0.98, r=0.98 and r=1.00 respectively). The fall in mean LA pressure (11.3 +/-
      7.9 mm Hg) and in mean PAW pressure (11.1 +/- 7.9 mm Hg) also correlated well.
      Correlation was good both before and after BMV when subgrouping was done based on
      average pulmonary vascular resistance and average LA mean pressure in each group.
      CONCLUSIONS: There is good correlation of PAW pressure with LA pressure even in
      the presence of pulmonary arterial or venous hypertension. It can replace LA
      pressure monitoring in any clinical setting.

PMID- 11584936
TI  - Efficacy and tolerability of oral enzyme therapy as compared to diclofenac in
      active osteoarthrosis of knee joint: an open randomized controlled clinical
      trial.
AB  - OBJECTIVE: To compare the efficacy and tolerability of an oral enzyme preparation
      (Phlogenzym) with that of an NSAID (diclofenac) in the treatment of active
      osteoarthrosis. METHODS: Prospective, randomized, controlled, single-blind study
      of seven weeks duration at a tertiary care centre wherein 50 patients aged 40-75
      years, with activated osteoarthrosis of knee joint were randomized to receive
      phlogenzym tablets (2-3 tablets, bid) or diclofenac sodium 50 mg bid for three
      weeks. RESULTS: At the end of therapy (three weeks) and at follow-up visit at
      seven weeks there was reduction in pain and joint tenderness and swelling in both
      groups, and slight improvement in the range of movement in the study group. The
      reduction in joint tenderness was greater (p < 0.05) in the study group receiving
      phlogenzym. CONCLUSION: Phlogenzym is as efficacious and well tolerated as
      diclofenac sodium in the management of active osteoarthrosis over three weeks of
      treatment.

PMID- 11584937
TI  - Carbon monoxide poisoning.
AB  - OBJECTIVES: We studied the clinical profile and autopsy findings of carbon
      monoxide (CO) poisoning encountered at a hospital located at the altitude of
      5,000 ft above mean sea level. METHODS: Clinical and postmortem findings in 25
      and 15 cases of accidental CO poisoning respectively were evaluated. The
      diagnosis was made on circumstantial evidences, definite history of "Bukhari"
      burning and positive Kunkel's test for carboxyhaemoglobin (COHb). Detailed
      routine investigations including pulse oxymetry, X-ray chest and
      electrocardiographical monitoring was carried out in all the 25 patients. Oxygen
      (100%) via an endotracheal tube in all the comatosed patients and by conventional
      non-rebreathing plastic face masks was the mainstay of treatment. All patients
      were monitored and followed up for any delayed neurological sequelae. RESULTS:
      Most of the patients were young adults and the duration of exposure varied
      between three to eight hours. The initial diagnosis was stroke in three, seizure
      in one, encephalitis in two and ischaemic heart disease (IHD) in four.
      Neurological and respiratory signs and symptoms were noted in 19 and 18 of 25
      patients respectively. SPO2 measured by pulse oxymetry was normal in all cases.
      ECG was suggestive of IHD in four patients. No delayed neurological sequelae was
      noted in any patients. Autopsy revealed deep red discoloration of skin and serous
      membranes in 80%, pulmonary oedema in 100% and cerebral oedema with widespread
      multiple pin point haemorrhages mainly in thalamus and globus pallidus in 40%.
      CONCLUSION: A high level of suspicion and routine history about the kind of
      indoor heating, specially in cold climate areas during winter will help in early
      diagnosis and decrease the incidence of misdiagnosis of CO poisoning. Oxygen
      (100%) or hyperbaric oxygen, if available should be administered without waiting
      for COHb levels to decrease morbidity and mortality.

PMID- 11584938
TI  - Comparison of accuracy and safety of computed tomography guided and unguided
      transthoracic fine needle aspiration biopsy in diagnosis of lung lesions.
AB  - OBJECTIVE: To study the accuracy and safety of CT guided and unguided
      transthoracic fine needle aspiration biopsy in diagnosis of lung lesions. METHOD:
      The study was carried out in 79 hospitalised patients during the period 1997
      1999. In 52 patients having peripheral and large sized lung lesion (> 5 cm in
      diameter) in chest X-ray unguided FNAB was performed and in the rest 27 patients
      having relatively central and small sized lesion (< 5 cm). CT guided FNAB was
      performed. Also in 15 patients having two times failed unguided aspiration, CT
      guided FNAB was performed. RESULTS: The diagnostic yield of unguided aspiration
      was 71.1% (37 out of 52). Out of 37 patients 29 (78.3%) had malignant lesion and
      eight (21.6%) non-malignant lesion. Sensitivity and specificity for detecting
      malignancy was 90.6% and 100% respectively. Complications were seen in 10
      patients (19.3%). Diagnostic yield of CT guided FNAB was 95.2% (40 out of 42), 33
      (82.5 %) had malignant lesion, seven (17.5%) had benign lesion. Sensitivity and
      specificity for detecting malignancy was 97.1% and 100% respectively. Minor
      complications were seen in three patients (7.1%). CONCLUSION: It was concluded
      that CT guided

PMID- 11584939
TI  - Medical disorders associated with endometrial carcinoma.
AB  - From January, 1990 to December, 1995, 113 cases of endometrial carcinoma were
      registered. Of them, 24 patients (20%) had associated medical disorders. A total
      of 37 medical disorders were found in these 24 patients. The distribution was as
      follows: diabetes mellitus in 15 patients, hypertension in 13 patients, coronary
      artery disease in two, asthma in one, RBBB in one and hypothyroidism in five
      patients. Age of the patients ranged from 48-76 years (Median 62 years). Fifteen
      patients underwent surgery and rest nine were inoperable due to medical
      illnesses. Eleven patients received radiotherapy and four received chemotherapy.
      Of the two failures, one developed metastasis to lung and another to bone. No
      local recurrence was observed. Median survival was 20 months. Late radiation
      morbidity was noticed in four patients (36%), all of them were diabetic.
      CONCLUSION: Hypothyroidism which was unexpectedly found in five patients may also
      be a risk factor associated with endometrial carcinoma. This finding has never
      been reported in the literature and it needs to be curiously studied in future
      series. The risk of late radiation complications is higher in diabetic patients.
      Overall prognosis of endometrial carcinoma associated with medical illnesses is
      not very good.

PMID- 11584940
TI  - Nitric oxide for clinicians.

PMID- 11584941
TI  - Pictorial CME. A thirty year man was rushed to the hospital after being stabbed
      in the back during a street fight.

PMID- 11584942
TI  - Sudden cardiac death in athletes.

PMID- 11584943
TI  - Clinical aspects of chronic arsenic toxicity.

PMID- 11584944
TI  - Barium carbonate poisoning mimicking Guillain-Barre syndrome.
AB  - Areflexic quadriplegia due to barium carbonate (rat poison) poisoning is
      described in two young patients. These cases very closely resembled Guillain
      Barre syndrome. The various effects of barium carbonate along with the
      pathogenesis of hypokalaemic paralysis are highlighted.

PMID- 11584945
TI  - Spinocerebellar ataxia--type 6.
AB  - Fifty six years lady presented with pure cerebellar ataxia with positive family
      history from paternal side presented to our clinic. DNA screening found to be
      SCA6. This is the first case report of SCA6 from India.

PMID- 11584946
TI  - Reversible dilated cardiomyopathy associated with thyrotoxicosis.

PMID- 11584947
TI  - Angiosarcoma of the heart presenting as recurrent cardiac tamponade.
AB  - We present an interesting case of angiosarcoma of the heart presenting as
      recurrent percardial effusion and cardiac tamponade.

PMID- 11584948
TI  - Weber Christian disease in a type 2 diabetic patient.

PMID- 11584949
TI  - Ossification of posterior longitudinal ligament causing cervical cord
      compression.
AB  - Ossification of the posterior longitudinal ligament (OPLL) is an uncommon cause
      of compressive myelopathy outside Japan. A case of cervical cord compression in a
      female whose MRI showed OPLL is reported. T2 weighted MRI images are the most
      effective to evaluate both spinal cord compression due to ossification and
      abnormal signal intensity of the cord. OPLL should be included in the
      differential diagnosis of cervical radiculomyelopathy.

PMID- 11584950
TI  - Biatrial tuberculosis.

PMID- 11584951
TI  - Systemic lupus erythematosus and myasthenia gravis.

PMID- 11584952
TI  - Erdheim-Chester disease.

PMID- 11584953
TI  - Gelatinous transformation of bone marrow.

PMID- 11584954
TI  - Oral hypoglycemics and azoles: an important drug interaction.

PMID- 11584955
TI  - Tuberculosis and Acquired Immunodeficiency Syndrome.

PMID- 11584956
TI  - Alpha interferon in systemic sclerosis.

PMID- 11584957
TI  - Study of hypothyroidism in Indian females with idiopathic oedema.

PMID- 11584958
TI  - A strange case of headache.

PMID- 11584959
TI  - Blood pressure changes during squatting--a study in normal subjects and its
      possible clinical significance.

PMID- 11584960
TI  - Pure red cell aplasia with thymoma.

PMID- 11584961
TI  - Prospective results of a standardized algorithm based on hemodynamic status for
      managing pediatric solid organ injury.
AB  - BACKGROUND: Controversy surrounds the need for ICU admission, prolonged bed rest,
      and the duration of activity restrictions for children sustaining blunt trauma.
      Adult literature supports management based on hemodynamic status, not CT grade.
      STUDY DESIGN: A 3-year prospective study of a standardized management algorithm
      for hemodynamically normal pediatric patients with blunt liver or spleen injury
      was performed. Patient selection was based on vital signs, irrespective of injury
      grade on CT. Patients requiring ICU admission for nonliver or nonspleen injury
      were excluded. Patients were admitted to a surgical ward with serial hematocrit
      levels. Discharge occurred 48 hours postinjury if patients had no abdominal
      tenderness, tolerated a regular diet, and had a stable hematocrit. Patients were
      allowed noncontact activity, including school, after discharge. Patients were
      followed up at 1 month with ultrasonographic imaging. RESULTS: Eighty-nine
      patients sustained blunt liver or spleen injury. Forty-five patients were
      excluded for other injuries (Glasgow Coma Scale < 13, 32 of 45); the remaining 44
      patients had a mean age of 8.9 years (range 2 to 17 years), Injury Severity Score
      10.6 (range 4 to 33), liver grade 2.1, and splenic injury grade 2.3. Mechanisms
      of injury were predominately motor vehicle collisions (59%). All patients were
      managed nonoperatively without transfusion; 43 of 44 patients completed the
      algorithm. Mean observation was 55.2 +/- 12.3 hours. One-month followup occurred
      in 33 of 44 patients, with one complication detected and no delayed bleeding.
      CONCLUSION: Management of pediatric solid organ injury should be guided by
      hemodynamic status and not injury grade on CT. Hemodynamically normal children
      can be safely managed without intensive care monitoring, do not need prolonged
      hospitalization, and can resume school on discharge.

PMID- 11584962
TI  - Multiinstitutional experience with the management of superior mesenteric artery
      injuries.
AB  - BACKGROUND: Superior mesenteric artery (SMA) injuries are rare and often lethal
      injuries incurring very high morbidity and mortality. The purposes of this study
      are to review a multiinstitutional experience with these injuries; to analyze
      Fullen's classification based on anatomic zone and ischemia grade for its
      predictive value; to correlate the American Association for the Surgery of Trauma
      Organ Injury Scale (AAST-OIS) for abdominal vascular injury with mortality; and
      to identify independent risk factors predictive of mortality, describing current
      trends for the management of this injury in America. DESIGN: We performed a
      retrospective multiinstitutional study of patients sustaining SMA injuries
      involving 34 trauma centers in the US over 10 years. Outcomes variables, both
      continuous and dichotomous, were analyzed initially with univariate methods. For
      the subsequent multivariate analysis, stepwise logistic regression was used to
      identify a set of risk factors significantly associated with mortality. RESULTS:
      There were 250 patients enrolled, with a mean Revised Trauma Score (RTS) of 6.44
      and a mean Injury Severity Score (ISS) of 25. Surgical management consisted of
      ligation in 175 of 244 patients (72%), primary [corrected] repair in 53 of 244
      patients (22%), autogenous grafts were used in 10 of 244 (4%), and prosthetic
      grafts of PTFE in 6 of 244 patients (2%). Overall mortality was 97 of 250
      patients (39%). Mortality versus Fullen's zones: zone I, 39 of 51 (76.5%); zone
      II, 15 of 34 (44.1%); zone III, 11 of 40 (27.5%); and zone IV, 25 of 108 (23.1%).
      Mortality versus Fullen's ischemia grade: grade 1, 22 of 34 (64.7%). Mortality
      versus AAST-OIS for abdominal vascular injury: grade I, 9 of 55 (16.4%); grade
      II, 13 of 51 (25.5%); grade III, 8 of 20 (40%); grade IV, 37 of 69 (53.6%); and
      grade V, 17 of 19 (89.5%). Logistic regression analysis identified as independent
      risk factors for mortality the following: transfusion of greater than 10 units of
      packed RBCs, intraoperative acidosis, dysrhythmias, injury to Fullen's zone I or
      II, and multisystem organ failure. CONCLUSION: SMA injuries are highly lethal.
      Fullen's anatomic zones, ischemia grade, and AAST-OIS abdominal vascular injuries
      correlate well with mortality. Injuries to Fullen's zones I and II, Fullen's
      maximal ischemia grade, and AAST-OIS injury grades IV and V, high-intraoperative
      transfusion requirements, and presence of acidosis and disrhythmias are
      significant predictors of mortality. All of these predictive factors for
      mortality must be taken into account in the surgical management of these
      injuries.

PMID- 11584963
TI  - Characterisitcs of patients having thyroid surgery under regional anesthesia.
AB  - BACKGROUND: Recently local/regional anesthesia has been reintroduced as an
      alternative to general anesthesia for thyroidectomy. This study was undertaken to
      analyze characteristics and outcomes of patients who had thyroid surgery
      performed under regional anesthesia compared with those who had thyroidectomy
      under general anesthesia. STUDY DESIGN: One hundred seventy-five consecutive
      patients who underwent thyroid surgery under regional or general anesthesia
      during a 3-year period were analyzed. Fifty-eight operations were performed under
      regional anesthesia and 116 under general anesthesia. Patient characteristics
      analyzed included age, gender, obesity, anesthesia class, and tumor pathology.
      Postoperative complications, including nausea or vomiting, were compared.
      Additionally, operative times and length of stay in each group were compared.
      RESULTS: Patient characteristics including age, gender, tumor pathology, and
      anesthesia class were similar in both groups. But only 2% of patients treated
      under regional anesthesia were obese compared with 23% under general anesthesia.
      Although not significant, there was a trend toward decreased incidence of nausea
      and vomiting in the regional group. Other complications for the regional and
      general anesthesia groups were equal at 3%. Two patients required conversion to
      general anesthesia. Complications in the general anesthesia group included one
      episode of transient symptomatic hypocalcemia, two patients with transient vocal
      cord paralysis, and one episode of hematoma. Finally, there was a statistically
      significant increase in total operating room time and length of stay for the
      general anesthesia group. CONCLUSIONS: Regional anesthesia is a safe alternative
      to general anesthesia for patients undergoing thyroid surgery. Patients who
      cannot communicate verbally with the surgical team or who are obese may not be
      ideal candidates for regional anesthesia. The use of regional anesthesia results
      in a decreased length of stay and similar operative and operating room times.

PMID- 11584964
TI  - Is there a role for incomplete resection in the management of retroperitoneal
      liposarcomas?
AB  - Complete surgical resection is the most effective modality for the treatment of
      retroperitoneal sarcomas. Previous studies of all types of retroperitoneal
      sarcomas have not shown a survival benefit of incomplete resection over no
      resection. Because death often occurs as a result of local progression in
      retroperitoneal liposarcomas (RPLS), it is possible that incomplete resection may
      be beneficial in this histologic type. In this study we have sought to determine
      the clinical outcomes in patients with incompletely resected and unresected RPLS
      with the aim of defining patients who may benefit from palliative resection. From
      a prospective clinical database 55 patients with incompletely resected (n = 43)
      or unresected (n = 12) RPLS were identified between 1982 and 1999. Statistical
      analyses were performed using the log-rank test and Kaplan-Meier estimates with
      disease-specific survival as the primary end point. Variables studied included
      age, gender, recurrent versus primary disease, tumor grade, and tumor size. The
      patient population consisted of 34 men and 21 women with a mean age of 61 +/- 14
      (SD) years. The median time to death was 10 months (range 1 to 83 months) with a
      median followup of 12 months (range 1 to 60 months) for survivors. Partial
      resection was an independent factor for increased survival as compared with
      exploration or biopsy only (median survival 26 versus 4 months, p < 0.0001). Of
      patients who received incomplete resections, locally recurrent presentation (n =
      19) versus primary disease (n = 24) was a negative prognostic variable (median
      survival 17 versus 46 months, p = 0.009). Successful palliation of symptoms was
      achieved in 24 of 32 patients (75%) with preoperative symptoms. In select
      patients with unresectable RPLS, incomplete surgical resection can provide
      prolongation in survival and successful symptom palliation. Most likely to
      benefit are those patients presenting with primary tumors, suggesting that
      surgical resection should be attempted in the majority of patients.

PMID- 11584965
TI  - Association of p53, p16, and vascular endothelial growth factor protein
      expressions with the prognosis and metastasis of gallbladder cancer.
AB  - BACKGROUND: Tumor suppressor genes were studied in gallbladder disease including
      cancer for correlation. VEGF (vascular endothelial growth factor) expression was
      assessed against Nevin staging and metastasis of gallbladder carcinoma. The
      importance of p53, p16, and VEGF in gallbladder cancer was estimated. STUDY
      DESIGN: Twenty-four gallbladder carcinomas, 20 gallbladder adenomas, and 18
      chronic cholecystitis specimens were immunohistochemically and
      histopathologically investigated for the relation of p53, p16, and VEGF to Nevin
      staging and pathologic grading. RESULTS: The expression rate of abnormal p53 in
      gallbladder carcinomas was significantly higher than that in gallbladder adenoma
      and chronic cholecystitis (p = 0.003, p = 0.014). The expression rate of abnormal
      p53 in Nevin staging S1, S2, S3 gallbladder carcinoma was significantly higher
      than that in S4, S5 (p = 0.01). Abnormal p16 was highest in carcinoma, next in
      adenoma, and lowest in chronic cholecystitis (p = 0.031, p = 0.017). Gallbladder
      carcinoma expressed VEGF far more often than adenoma or cholecystitis (p =
      0.001); VEGF-positive rates were lower in S1, S2, S3 than S4, S5 by Nevin staging
      of gallbladder cancer (p = 0.044). CONCLUSION: Mutation of p53 and p16 genes
      might correlate with progression of of gallbladder carcinoma. Analysis of p53 and
      p16 can estimate the prognosis of gallbladder cancer. VEGF expression correlates
      with Nevin staging in gallbladder cancer.

PMID- 11584966
TI  - Intrahepatic cholangiocarcinoma: resectability, recurrence pattern, and outcomes.
AB  - Intrahepatic cholangiocarcinoma (IHC) is a rare primary hepatic tumor of bile
      duct origin for which resection is the most effective treatment. But
      resectability, outcomes after resection, and recurrence patterns have not been
      well described. Patients with IHC were identified from a prospective database.
      Demographic data, tumor characteristics, and outcomes were analyzed. From March
      1992 to September 2000, 53 patients with hepatic tumors underwent exploration and
      were found to have pure IHC on pathologic analysis. Patients with mixed
      hepatocellular and cholangiocarcinoma tumors were excluded. At exploration, 20
      patients were unresectable for an overall resectability rate of 62% (33 of 53).
      Median survival for patients submitted to resection was 37.4 months versus 11.6
      months for patients undergoing biopsy only (p = 0.006; median followup for
      surviving patients, 15.6 months). Actuarial 3-year survival was 55% versus 21%,
      respectively. Factors predictive of poor survival after resection included
      vascular invasion (p = 0.0007), histologically positive margin (p = 0.009), or
      multiple tumors (p = 0.003). After resection, 20 of 33 patients (61%) recurred at
      a median of 12.4 months. Sites of recurrence included the liver (14),
      retroperitoneal or hilar nodes (4), lung (4), and bone (2). The median disease
      free survival was 19.4 months, with a 3-year disease-free survival rate of 22%.
      Factors predictive of recurrence were multiple tumors (p = 0.0002), tumor size (p
      = 0.001), and vascular invasion (p = 0.01). About two-thirds of patients who
      appeared resectable on preoperative imaging were amenable to curative resection
      at the time of operation. Although complete resection improved survival,
      recurrence was common. The majority of recurrences were local or regional, which
      may help guide future adjuvant therapy strategies.

PMID- 11584967
TI  - Magnetic resonance imaging and abdominal wall hernias in aortic surgery.
AB  - BACKGROUND: The aim of this study was to evaluate the incidence of abdominal wall
      hernias (AWH) in patients operated on for abdominal aortic aneurysm (AAA)
      compared with patients treated for aortoiliac occlusive disease. The efficacy of
      MRI in early diagnosis of AWH also was studied. STUDY DESIGN: One hundred
      fourteen patients operated for either AAA (51 patients, group A) or aortoiliac
      occlusive disease (63 patients, group B) constitute the study. The presence of
      AWH onset was evaluated by clinical observation followed by ultrasonography. Data
      acquired by ultrasonography were compared with those obtained by MRI to determine
      the efficacy of this diagnostic tool in all 114 patients. The prevalence of
      inguinal hernias in both groups also was determined. RESULTS: A significant
      difference was found in the incidence of AWH. AWH developed in 31.7% (16 of 51)
      of group A patients and 17.4% (11 of 63) of group B patients (p < 0.03). A
      significant prevalence ofinguinal hernias was detected in group A (p < 0.01). The
      Cox hazard regression analysis revealed as independent predictors of
      postoperative AWH only the presence of AAA and a history of laparotomy.
      CONCLUSIONS: Ours and other studies recall collagen synthesis disorders to
      explain the statistical association observed among AAA, inguinal hernias, and
      AWH. MRI, especially in patients at risk, appears to be an effective diagnostic
      approach to early detection of AWH.

PMID- 11584968
TI  - The assessment of fecal incontinence in women.

PMID- 11584969
TI  - Infection control in the operating room: current practices or sacred cows?

PMID- 11584970
TI  - Training to serve unmet surgical needs worldwide.

PMID- 11584971
TI  - Complications and results of primary minimally invasive antireflux procedures: a
      review of 10,735 reported cases.

PMID- 11584972
TI  - Multidisciplinary management of perihilar bile duct cancer.

PMID- 11584973
TI  - Communication: part of the surgical armamentarium.

PMID- 11584974
TI  - Intermuscular lipoma.

PMID- 11584975
TI  - Circumferential giant leiomyoma of the esophagus.

PMID- 11584976
TI  - Laparoscopic prostatectomy.

PMID- 11584977
TI  - Caesarean delivery and celiotomy using panniculus retraction in the morbidly
      obese patient.

PMID- 11584978
TI  - Breast lymphatic mapping.

PMID- 11584979
TI  - Antithrombotic therapy.

PMID- 11584980
TI  - Practice patterns in sentinel lymph node biopsy.

PMID- 11584981
TI  - Anticholinergic effects of medication in elderly patients.
AB  - Anticholinergic toxicity is a common problem in the elderly. It has many effects
      ranging from dry mouth, constipation, and visual impairments to confusion,
      delirium, and severe cognitive decline. The toxicity is often the result of the
      cumulative anticholinergic burden of multiple prescription medications and
      metabolites rather than of a single compound. The management of elderly patients,
      particularly those suffering from dementia, should therefore aim to reduce the
      use of medications with anticholinergic effects.

PMID- 11584982
TI  - Movement disorders associated with neuroleptic treatment.
AB  - Neuroleptic-induced movement disorders, or extrapyramidal side effects (EPS), can
      be classified into acute and tardive syndromes. Among the former are
      parkinsonism, dystonia, and akathisia. Conventional neuroleptics that have
      traditionally been used to treat psychiatric disorders are often associated with
      EPS. The newer atypical antipsychotics provide a more promising treatment
      strategy for psychiatric disorders and have a lower potential for producing EPS
      than conventional neuroleptics.

PMID- 11584983
TI  - Scales to assess efficacy and safety of pharmacologic agents in the treatment of
      behavioral and psychological symptoms of dementia.
AB  - Advances in the assessment of the behavioral and psychological symptoms of
      dementia (BPSD) have been employed in large-scale clinical trials of new
      antipsychotic medications such as risperidone. These scales can be used to assess
      drug efficacy and to compare different treatment regimens. We review 3 valid and
      reliable scales, the Behavioral Pathology in Alzheimer's Disease Rating Scale
      (BEHAVE-AD), the Cohen-Mansfield Agitation Inventory (CMAI), and the
      Neuropsychiatric Inventory (NPI). Extrapyramidal side effects (EPS) associated
      with the treatment of BPSD have also been assessed using a number of rating
      instruments. The design of the most comprehensive of these, the Extrapyramidal
      Symptom Rating Scale (ESRS), is exhaustive, and it successfully quantifies EPS
      and distinguishes toxic from nontoxic medications. This publication serves as an
      aid to researchers and clinicians in their interpretation of qualitative and
      quantitative data from trials evaluating antipsychotic agents in the treatment of
      BPSD.

PMID- 11584984
TI  - Underlying mechanisms of psychosis and aggression in patients with Alzheimer's
      disease.
AB  - It is well known that serotonergic function is related to aggression. Patients
      with Alzheimer's disease exhibit aggressive behavior, and alterations in their
      serotonergic function have been identified. Recent clinical trials involving new
      antipsychotic agents, such as risperidone, which has both serotonergic and
      dopaminergic activity, have demonstrated the efficacy and safety of these drugs
      in treating the psychosis and aggressive behavior associated with dementia.

PMID- 11584985
TI  - Long-term safety of risperidone.
AB  - In 2 pivotal trials comparing risperidone with placebo, the risk of adverse
      events was similar in both treatment groups when risperidone was given at the
      optimal clinical dose (1 mg/day). During 12-month, open-label extensions to these
      studies, the incidence of de novo tardive dyskinesia was very low. No clinically
      significant adverse events, changes in vital signs, or laboratory signs were
      observed. In summary, the safety and tolerability of risperidone in treating
      elderly dementia sufferers has been favorable in several clinical trials.

PMID- 11584986
TI  - Risperidone for the treatment of behavioral and psychological symptoms of
      dementia.
AB  - Risperidone offers physicians the unique combination of extensive, published
      clinical experience and a good safety profile for treating patients with dementia
      who have symptoms of aggression, agitation, and psychosis. Numerous open-label
      and, more recently, placebo-controlled trials have documented the efficacy of
      risperidone in the management of behavioral and psychological symptoms of
      dementia. These trials also show that risperidone is better tolerated than
      conventional neuroleptic agents. Comparatively, patients treated with risperidone
      experience substantially fewer side effects, including extrapyramidal symptoms,
      cognitive toxicity, and tardive dyskinesia.

PMID- 11584987
TI  - Behavioral and psychological symptoms of dementia: a current focus for
      clinicians, researchers, and caregivers.
AB  - Behavioral and psychological symptoms of dementia are an important aspect of
      dementing illness. They represent a growing burden to caregivers and health care
      institutions and an increasing financial burden as the proportion of elderly
      patients, and consequently those with dementia, increases throughout the world.
      Behavioral and psychological symptoms of dementia can be recognized and assessed
      using a number of rating scales. Management of the symptoms is then possible for
      the benefit of patients, family members, caregivers, and the health care system.

PMID- 11584988
TI  - Adverse effects of atypical antipsychotics.
AB  - Atypical antipsychotics have the potential to cause weight gain and derangement
      of glucose metabolism. These side effects can lead to obesity, diabetes mellitus,
      and dyslipidemia and should be considered in the management of the behavioral and
      psychological symptoms of dementia.

PMID- 11584989
TI  - Genitourinary fungal infections: a therapeutic conundrum.
AB  - Fungi cause 8% of nosocomial infections. This is caused, in part, by the
      increasing pool of immunocompromised patients. Elderly, transplant and HIV
      patients, as well as premature infants, have become prime candidates for invasive
      fungal infections. The widespread use of broad spectrum antibiotics plays a role.
      Utilisation of appropriate antifungal treatment modalities requires an
      understanding of the pathogenesis of infection. This is a challenging problem as
      fungi can cause different clinical manifestations that depend on the type of
      fungal species and patient response to the infection. Although Candida spp. are
      the most frequent pathogen, other species such as Aspergillus and Cryptococcus
      have become major pathogens. Environmental fungi which include Blastomyces,
      Coccidioides and Histoplasma have become more aggressive in the vulnerable
      patient. The genitourinary system can be a source or target of disseminated
      fungal infection. Diagnosis depends on clinical awareness, utilisation of
      appropriate diagnostic modalities, imaging modalities and a thorough clinical
      assessment. The treatment of primary (Blastomyces, Coccidioides, Histoplasma)
      infection generally requires amphotericin B (AmpB). The opportunistic infections
      (Aspergillus, Cryptococcus and Candida) may respond to the triazoles although
      AmpB remains the 'gold standard'. Infections caused by Candida spp. represents
      the greatest challenge to the clinician. The presence of Candida spp. in the
      urine may indicate colonisation or infection. Untreated, Candida can remain as a
      'saprophyte' or develop ascending infection, sepsis or death. The prophylactic
      use of fluconazole may in itself result in resistant infection, hence the
      'conundrum'.

PMID- 11584990
TI  - Fluoroquinolones in the treatment of acute uncomplicated urinary tract infections
      in adult women.
AB  - Urinary tract infections (UTIs) are among the most commonly encountered bacterial
      infections. Acute uncomplicated UTIs in adults include episodes of cystitis and
      pyelonephritis. The main uropathogens causing uncomplicated UTIs have, in the
      past, been fairly predictable and they have generally been susceptible to several
      commonly used oral antimicrobials. There has been a trend, however, towards
      increasing antimicrobial resistance among uropathogens over the past few years,
      especially to beta-lactams and trimethoprim-sulfamethoxazole (TMP-SMX). The
      current standard of therapy for the empiric treatment of acute uncomplicated
      cystitis is TMP-SMX for 3 days. Since the prevalence of resistance to TMP-SMX
      among uropathogens is increasing, however, fluoroquinolones, with their low side
      effect profile, convenient pharmacokinetics and effectiveness, are increasingly
      being used first-line for the management of cystitis. Treatment of acute
      pyelonephritis is less controversial and fluoroquinolones are recommended as
      first-line agents in the empiric treatment of community-acquired pyelonephritis.
      Of concern, the increased use of fluoroquinolones for the treatment of UTIs and
      other infectious processes has resulted in an increasing prevalence of
      fluoroquinolone-resistant uropathogens worldwide. In light of these changing
      resistance patterns, prudent use of fluoroquinolones for the treatment of UTIs is
      warranted.

PMID- 11584991
TI  - Current status of antiretroviral therapies.
AB  - The availability of potent antiretroviral drugs and their use in combination
      regimens has led to a dramatic decline in the morbidity and mortality associated
      with HIV infection. Currently, there are 15 FDA-approved antiretrovirals
      categorised into three classes of drugs. Several others are in various stages of
      basic and clinical development.

PMID- 11584992
TI  - Cytomegalovirus treatment options in immunocompromised patients.
AB  - Cytomegalovirus (CMV) infection was recognised in congenitally infected infants
      in the first half of the 20th century. Following the increased use of
      immunosuppressive regimens for bone marrow and solid organ transplantation,
      various manifestations of CMV disease were recognised. Milder symptoms included
      fever, anorexia and malaise but severe symptoms included pneumonitis, hepatitis,
      gastrointestinal ulceration, choreoretinitis and encephalopathy, all with a high
      morbidity or mortality. With the onset of the AIDS epidemic, manifestations of
      CMV became evident, predominantly retinitis. Ganciclovir used intravenously has
      been the principal anti-CMV agent investigated. However, ganciclovir has problems
      with suboptimal efficacy, toxicity, poor oral bioavailability and evolution of
      resistant strains. Additional studies have been performed on foscarnet and
      cidofovir, although the use of both have been limited by their nephrotoxicity.
      Combination therapy with ganciclovir and foscarnet for resistant strains has been
      used. There are promising newer drugs like the methylenecyclopropane nucleoside
      analogues and benzimidazole. The most novel compound is the antisense
      oligonucleotide fomivirsen that has been evaluated principally in CMV retinitis.
      The role of immunotherapy with either immunoglobulin prophylaxis or the novel
      adoptive immunotherapy needs further evaluation.

PMID- 11584993
TI  - Treatment of acute cryptococcal disease.
AB  - Successful treatment outcome for cryptococcal disease has been available since
      the introduction of the polyene antifungal, amphotericin B. Over the past 15-20
      years, treatment of acute cryptococcal disease has dramatically improved. Several
      therapeutic strategies have been introduced which improve overall outcome of
      therapy and help decrease the duration of treatment. Not surprisingly, most data
      now exists on the treatment of AIDS-associated cryptococcal disease, especially
      cryptococcal meningitis. Currently, amphotericin B with or without flucytosine is
      regarded as the best initial therapy for patients with meningitis or more severe
      illness, although, the azoles and other formulations of amphotericin B can
      considered in other situations. The choice of treatment for cryptococcal disease
      depends on both the anatomic sites of involvement and the host's immune status,
      all of which will be addressed in this article.

PMID- 11584994
TI  - Options for the pharmacotherapy of toxoplasmosis during pregnancy.
AB  - Toxoplasmosis infection during pregnancy can cause stillbirths, severe mental
      retardations or ocular disorders that can also occur later in life and have a
      potential to relapse. As the disease is generally asymptomatic, diagnosis relies
      on serological tests. Primary prevention intends to prevent the infection of the
      fetus, while secondary prevention aims at reducing the severity of sequelae.
      Preventive attitudes regarding congenital toxoplasmosis differ according to
      countries. In Austria and France, a nationwide programme based on the screening
      of seronegative pregnant women and the treatment of all seroconversions has been
      implemented. The UK and Norway have rejected such a screening due to the lack of
      evidence of its efficacy. A review of published studies showed that no randomised
      controlled trials have been conducted. The only available data come from
      retrospective studies and are methodologically flawed. The impact of chemotherapy
      on primary and secondary prevention still needs to be assessed. This lack of
      evidence results in conflicting attitudes that increase the anxiety already
      raised in pregnant women and doctors by the occurrence of a maternal
      toxoplasmosis during pregnancy. Before making any change in preventative
      strategy, it is of utmost importance to increase our knowledge on treatment
      efficacy through proper randomised trials of existing drugs and of new
      potentially active compounds.

PMID- 11584995
TI  - Current pharmacotherapy of pertussis.
AB  - Human infection with Bordetella pertussis and Bordetella parapertussis causes
      significant morbidity and mortality. While universal immunisation represents the
      mainstay of prevention, the purpose of this review is to summarise the current
      options for antimicrobial chemotherapy of pertussis. Several chemotherapeutic
      approaches have an important place in therapy and in infection control.
      Supportive treatment including nasopharyngeal suction, oxygen and parenteral
      fluids, is essential for infants < 1 year who are at greatest risk of
      complications and permanent sequelae. Steroids and beta2-agonists are also used
      in the management of severe neonatal pertussis. Several antibiotics have been
      shown to reduce the level of bacterial colonisation of the respiratory tract,
      however, erythromycin is accepted to be the treatment of choice. Erythromycin
      reduces severity and duration of disease, even if started during the paroxysmal
      phase. A 14 day course is recommended although side effects may limit compliance;
      a recent study indicates that a 7 day course may have similar efficacy in terms
      of eradication and prevention of relapse. Alternatives to erythromycin are
      clarithromycin, azithromycin and trimethoprim-sulfamethoxazole. Fluoroquinolones
      have good in vitro activity against both B. pertussis and B. parapertussis and
      may be useful in the treatment of adult patients with pertussis, although there
      are no supporting clinical data at present. Erythromycin prophylaxis is also
      recommended for close household contacts of patients with pertussis.

PMID- 11584996
TI  - Current treatment practice of herpes zoster.
AB  - The management of herpes zoster infection has been impacted by the development of
      oral and iv. antiviral therapies. There are clinical and historical features that
      help optimise the particular therapy course for a given patient. Additionally,
      there are common features of management in all patients with herpes zoster. In
      this review an understanding of the pathogenesis of herpes zoster is utilised as
      a starting point for the development of a rational approach to therapy. Clinical
      findings that impact decision making are emphasised and the appropriate goals for
      therapy are discussed.

PMID- 11584997
TI  - Current pharmacotherapy for hepatitis B infection.
AB  - Chronic infection with the hepatitis B virus (HBV) affects 350 million people
      worldwide, or approximately 5% of the global population, and commonly results in
      cirrhosis and hepatocellular carcinoma. Until recently, the only available
      treatment was injectable interferon alpha and response rates were suboptimal.
      Moreover, this expensive and toxic therapy had little applicability in the
      endemic regions of the world, i.e., Asia and Africa. The realisation that orally
      available nucleoside and nucleotide agents may effectively control this infection
      opened a new era in the management of chronic hepatitis B. Oral lamivudine
      recently became approved for treatment of hepatitis B worldwide. It is free of
      significant toxicity, improves liver histology and rapidly diminishes HBV DNA
      levels; lamivudine is expected to become the first-line therapy of choice.
      Nevertheless, the consistent emergence of lamivudine-resistant variants mandates
      the need to develop additional therapeutic agents. Adefovir dipivoxil, a
      nucleotide, and entecavir, a nucleoside agent, are promising new drugs that might
      eventually be used in combination with lamivudine and therefore reduce the
      incidence of drug resistance. There is a critical need to advance the research of
      hepatitis B antiviral agents so that effective combination therapies can become
      widely available.

PMID- 11584998
TI  - Treatment of platinum-resistant ovarian cancer.
AB  - In the United States, almost 70% of the 23,000 women diagnosed annually with
      epithelial ovarian cancer present with advanced disease (FIGO stages III-IV).
      Primary therapy for these patients includes surgical cytoreduction and 6-8
      courses of platinum- and taxane-based chemotherapy. Although 90% of patients will
      respond to this multi-modality combination regimen, most patients will experience
      recurrences. The 5 year survival for women with stage III disease is 15-30% and 0
      20% for those with stage IV disease. Medical and gynecological oncologists,
      therefore, must be prepared to treat many women with recurrent ovarian cancer.

PMID- 11584999
TI  - Peginterferon alpha-2b: a new approach to improving response in hepatitis C
      patients.
AB  - Chronic hepatitis C infection affects approximately four million Americans. Over
      the last decade, Type 1 interferons (IFNs) have been the mainstay of therapy for
      suitable patients. Recently, the combination of IFN plus ribavirin, with enhanced
      response rates, has replaced IFN monotherapy for treatment of these patients. The
      addition of a polyethylene glycol (peg) moiety to IFN alpha-2b has provided a
      drug with reduced clearance whilst retaining biological and antiviral activity.
      This formulation allows once-weekly dosing and enhances sustained response rates,
      without significantly changing the safety and tolerability of IFN. Clinical
      trials indicate a doubling of sustained virological response rates for regimens
      utilising pegIFN alpha-2b, compared with standard IFN-alpha 2b. The combination
      of pegIFN alpha-2b and ribavirin further increases the sustained virological
      response rates to > 50% for suitable patients. Future pegIFN alpha-2b studies
      will need to examine drug profiles in patients with co-morbid conditions (e.g.,
      renal impairment, liver transplantation), as well as safety and efficacy issues
      in different ethnic groups. Further clinical trials are also required to
      determine the benefits of pegIFN alpha-2b in previous non-responders or relapse
      patients and as maintenance therapy to prevent disease progression. Finally,
      careful cost effectiveness analyses will need to be performed.

PMID- 11585000
TI  - Ribavirin--current status of a broad spectrum antiviral agent.
AB  - Ribavirin is a very broad-spectrum virustatic antiviral agent, first synthesised
      in 1972. It is characterised by low toxicity apart from reversible anaemia,
      usually mild. Its multiple mechanisms of action mean that viral resistance rarely
      develops. It can be administered orally, intravenously, or via a nebuliser. It
      has shown varying degrees of clinical efficacy in a variety of human diseases
      including respiratory tract infections due to respiratory syncytial virus and
      influenza, measles, herpesvirus infections, HIV infection, Lassa fever,
      haemorrhagic fever with renal syndrome, and (in combination with IFN-alpha)
      chronic hepatitis C infection. It may well prove of value against other emerging
      exotic infections (e.g., West Nile virus, Nipah virus).

PMID- 11585001
TI  - Dalteparin sodium.
AB  - Dalteparin sodium (Fragmin, Pharmacia Corporation) is a low molecular weight
      heparin (LMWH) with a mean molecular weight of approximately 5000 Da. As with the
      other LMWHs, dalteparin sodium has certain advantages over unfractionated heparin
      (UFH), most important of which are improved bio-availability by sc. injection, a
      prolonged antithrombotic activity which is highly correlated with body weight
      permitting the o.d. administration of the drug. Dalteparin sodium has been
      subjected to a large number of well-designed randomised clinical trials for the
      prevention and treatment of thrombotic disorders. Based on data from the
      randomised clinical trials, dalteparin sodium has been approved internationally
      for a wide spectrum of clinical indications (e.g., prevention of thromboembolic
      events after surgery). Dalteparin sodium has also been studied in randomised
      controlled trials in the maintenance of graft patentcy following peripheral
      vascular surgery, in place of warfarin for the long-term treatment of patients
      presenting with deep vein thrombosis (DVT), in the prevention of upper extremity
      thrombosis in patients with indwelling portacath devices and in pregnant patients
      with a history of previous venous thromboembolism with or without thrombophilia.
      Dalteparin sodium has been compared with heparin for the prevention of thrombotic
      complications during haemodyalisis and haemofiltration. These studies have shown
      promising results but further work is required before dalteparin sodium can be
      recommended for these indications.

PMID- 11585002
TI  - The 2nd International Workshop on Clinical Pharmacology of HIV Therapy. April 2nd
      4th 2001, Noordwijk, The Netherlands.
AB  - The 2nd International Workshop on Clinical Pharmacology of HIV Therapy was
      convened in Noordwijk, The Netherlands on April 2nd-4th, 2001. The purpose of
      this meeting was to present and discuss research related to antiretroviral drug
      interactions, drug distribution to sanctuary sites, pharmacokinetics,
      pharmacodynamics (i.e., the relationship between pharmacokinetics and efficacy,
      toxicity or drug resistance), inhibitory quotient (IQ) and therapeutic drug
      monitoring (TDM). There were 28 oral and 49 poster presentations accepted to this
      meeting. While most studies focused on protease inhibitors (PIs), insight into
      the pharmacology of non-nucleoside reverse transcriptase inhibitors (NNRTIs) was
      also gleaned. Herein, we highlight some of the research that was presented.

PMID- 11585003
TI  - Intravesical valrubicin in the treatment of carcinoma in situ of the bladder.
AB  - The propensity of patients with carcinoma in situ (CIS) of the bladder to
      progress to invasive and metastatic disease is clearly established. Today, the
      standard therapy in treating patients with CIS of the bladder is intravesical
      bacillus Calmette-Guerin (BCG). Nevertheless, patients who fail intravesical BCG
      have few viable options except to undergo a radical cystectomy. Valrubicin (N
      trifluoroacetyladriamycin-14-valerate) is a new semisynthetic derivative of the
      anthracycline antibiotic doxorubicin that has been shown to benefit patients with
      BCG-refractory CIS of the bladder. Intravesical instillation of valrubicin is
      well-tolerated, safe and can be durable. Early non-randomised studies show
      promise and the current utilisation of this drug is limited to patients with BCG
      refractory CIS of the bladder who are not good surgical candidates. Randomised
      studies of intravesical valrubicin for the treatment of superficial bladder
      cancer are ongoing.

PMID- 11585004
TI  - Infliximab.
AB  - Infliximab (Remicade, Centocor, Inc.) is an intravenously administered monoclonal
      antibody to TNF proven effective in the treatment of moderate to severe Crohn's
      disease (CD). Its introduction in October 1998 was heralded by some as the most
      important addition to therapy for this condition in 50 years. Since then,
      additional indications have been added as efficacy has been proven in fistulising
      CD and in rheumatoid arthritis. Even though the costs associated with a single
      dose are several thousand US dollars, more than 150,000 patients have received
      infusions since its approval.

PMID- 11585005
TI  - Nateglinide: a new rapid-acting insulinotropic agent.
AB  - The United Kingdom Prospective Diabetes Study has shown that tight glycaemic
      control significantly reduces microvascular complications in Type 2 diabetes, but
      the effects on macrovascular complications were less impressive and did not reach
      statistical significance. Epidemiological studies have shown that post-prandial
      hyperglycaemia, rather than fasting hyperglycaemia, is more closely related to
      cardiovascular complications. It is, therefore, possible that previous studies
      may have overlooked the possible benefits of tight control of post-prandial
      hyperglycaemia as an important factor in reducing the cardiovascular mortality.
      Nateglinide is a novel D-phenylalanine derivative that inhibits ATP-sensitive K+
      channels in pancreatic beta-cells in the presence of glucose and thereby restores
      first phase insulin response in patients with Type 2 diabetes. This helps in
      reducing post-prandial glucose excursion. Combination studies with metformin have
      shown it to be effective in controlling hyperglycaemia. While metformin reduces
      the basal plasma glucose, nateglinide helps in controlling post-prandial peaks.
      Nateglinide provides a new therapeutic option for treating Type 2 diabetes by
      specifically targeting post-prandial hyperglycaemia.

PMID- 11585006
TI  - Ziprasidone: a new atypical antipsychotic.
AB  - This paper reviews the clinical pharmacology, efficacy and safety of the new
      atypical antipsychotic, ziprasidone. All published citations regarding
      ziprasidone were retrieved and reviewed using a MEDLINE search (completed for
      citations to early 2001). In addition, abstracts from recent scientific meetings
      presenting data not yet published were reviewed. Like other new antipsychotic
      medications, ziprasidone fits the profile of an atypical agent, exerting efficacy
      in positive and negative symptoms of psychosis, as well as affective symptoms,
      with a low risk of neurological and neuroendocrinological side effects. Unlike
      newer agents, it does not appear to be associated with weight gain in most
      patients.

PMID- 11585007
TI  - Innovative cancer drug targets: genomics, transcriptomics and clinomics.

PMID- 11585008
TI  - Photodynamic therapy in oncology.
AB  - Photodynamic therapy (PDT) is a cancer treatment modality that is based on the
      administration of a photosensitiser, which is retained in tumour tissues more
      than in normal tissues, followed by illumination of the tumour with visible light
      in a wavelength range matching the absorption spectrum of the photosensitiser.
      The photosensitiser absorbs light energy and induces the production of reactive
      oxygen species in the tumour environment, generating a cascade of events that
      kills the tumour cells. The first generation photosensitiser, Photofrin
      (porfirmer sodium), has been approved for oesophageal and lung cancer in the US
      and has been under investigation for other malignant and non-malignant diseases.
      Sub-optimal light penetration at the treatment absorption peak of Photofrin and
      prolonged skin photosensitivity in patients are limiting factors for this
      preparation. Several new photosensitisers have improved properties, especially
      absorption of longer wavelength light which penetrates deeper into tissue and
      faster clearance from normal tissue. This paper reviews the current use of first-
      and second-generation photosensitisers in oncology. The use of PDT in oncology
      has been restricted to certain cancer indications and has not yet become an
      integral part of cancer treatment in general. The main advantage of PDT is that
      the treatment can be repeated multiple times safely, without producing
      immunosuppressive and myelosuppressive effects and can be administered even after
      surgery, chemotherapy or radiotherapy. The current work on new photosensitisers
      and light delivery equipment will address some of the present shortcomings of
      PDT. Much has been learned in recent years about the mechanisms of cellular and
      tissue responses to PDT and protocols designed to capitalise on this knowledge
      showed lead to additional improvements.

PMID- 11585009
TI  - Nucleoside analogues in the treatment of haematological malignancies.
AB  - The nucleoside analogues are a group of antimetabolite cytotoxics which generally
      have to be metabolised to the equivalent nucleotide before incorporation into
      DNA. Cytarabine is a well established component of the treatment of acute
      leukaemias and has its principal action on dividing cells. New formulations
      include a liposome encapsulated product for intrathecal use and oral cytarabine
      ocfosfate which may be suitable for long-term outpatient use. Pentostatin acts by
      causing accumulation of deoxynucleotides and, although active against hairy cell
      leukaemia, is associated with a poor tolerance profile. Cladribine and
      fludarabine have substantial activity in the treatment of chronic lymphocytic
      leukaemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). Fludarabine is the
      more thoroughly investigated of the two and is currently being developed in
      combination therapies for CLL and NHL and also in a combination with cytarabine
      for acute myeloid leukaemia. Fludarabine's immunosuppressive activity is being
      exploited in the conditioning of patients for non-myeloablative stem cell
      transplantation. Gemcitabine is an established agent in the treatment of a number
      of solid tumours but also has activity in haematological malignancies which might
      be exploited by the use of extended infusion schedules. Newer agents including
      nelarabine, clofarabine and troxacitabine are undergoing clinical evaluation and
      show promising activity.

PMID- 11585010
TI  - Treatment options in Waldenstrom's macroglobulinaemia: the role of the purine
      analogues.
AB  - The purine nucleoside analogues, either alone or in combination with other
      chemotherapeutic agents, are increasingly used in the treatment of patients with
      indolent B-cell lymphoproliferative disorders. The initial studies in
      Waldenstrom's macroglobulinaemia (WM) are very promising. Approximately 40% of
      patients who have received prior therapy with alkylating agents respond, while
      response rates of up to 90% have been documented in untreated patients. However,
      it is not known whether the purine analogues offer any significant advantage over
      alkylating agents such as chlorambucil. In this review the treatment options in
      WM and in particular the role of the purine analogues are discussed.

PMID- 11585011
TI  - Antibody therapy of lymphoma.
AB  - The availability of rituximab and the possible imminent availability of two new
      radiolabelled monoclonal anti-CD20 antibodies (Yttrium-90 (90Y)-ibritumomab and
      Iodine-131(131I)-tositumomab) have captured much attention in the treatment of
      lymphoma. The chimeric monoclonal anti-CD20 antibody, rituximab has truly
      heralded a new era for the treatment of lymphoma and human malignancies. The full
      potential of antibody-based therapy to improve the outcome in patients with B
      cell non-Hodgkin's lymphoma has yet to be defined, but recent data suggests that
      the combination of chemotherapy plus rituximab may significantly improve outcome
      for patients with aggressive lymphoma over chemotherapy alone. Highly promising
      data are also emerging for the use of rituximab in combination with chemotherapy
      in other types of lymphoma. New advances in antibody therapy, driven by new
      technologies and defining novel antigen targets, offer the promise of more
      effective tumour specific therapies. Combinations of antibodies, either
      conjugated with radioisotopes or unlabelled, used with chemotherapy are likely to
      provide definitive advances in the treatment of lymphoma in the immediate future.

PMID- 11585012
TI  - Role of taxanes in the combined modality treatment of patients with locally
      advanced non-small cell lung cancer.
AB  - The plant-derived taxanes have a unique mechanism of cytotoxic action and have
      shown interesting response and survival data in metastatic non-small cell lung
      cancer (NSCLC). Based on these results, taxane-based regimens have been
      investigated in combination with radiotherapy in unresectable NSCLC. Trials with
      paclitaxel-based concurrent chemoradiotherapy have shown 50-100% tumour response
      rates, 12-26 month median survivals and 32-52% 2-year survival rates. Trials with
      concurrent chemoradiotherapy with docetaxel have shown 35-92% tumour response
      rates, 12-23 month median survivals, and 41-43% 2 year survival rates. Taxane
      based concurrent chemoradiotherapy for stage III NSCLC appears promising. Large
      ongoing randomised trials will define the role of these agents in the treatment
      of locally advanced NSCLC.

PMID- 11585013
TI  - New drugs in breast cancer.
AB  - The 1990s have seen the emergence of several classes of new efficacious drugs
      which have become established as treatment for breast cancer. Thus, aromatase
      inhibitors, taxanes and herceptin have all emerged as potentially valuable
      therapeutic agents for treatment of advanced breast cancer. Bisphosphonates have
      found a place in preventing skeletal complications in breast cancer patients with
      bone metastasis. Tamoxifen has a new role in chemoprevention in patients at high
      risk of breast cancer. This paper summarises these results.

PMID- 11585014
TI  - Aromatase inhibitors for breast cancer: pharmacoeconomic considerations.
AB  - Although the anti-oestrogen tamoxifen is recognised as the treatment of choice
      for both premenopausal and postmenopausal women with advanced hormone-dependent
      breast cancer, oestrogen deprivation can also be achieved, with apparently less
      adverse-effects, through selective inhibition of aromatase. Recent clinical
      trials have demonstrated the efficacy and tolerability of the new generation of
      aromatase inhibitors as second-line and first-line therapy in postmenopausal
      women with breast cancers who were eligible for endocrine treatment. Speculating
      that administration of aromatase inhibitors will not be limited to postmenopausal
      breast cancer, a pharmacoeconomic perspective is considered based on available
      data and putative therapeutic application during various phases of the disease.

PMID- 11585015
TI  - Diastolic dysfunction: insights into pathophysiology and pharmacotherapy.
AB  - This review focuses on diastolic dysfunction with special emphasis on isolated
      diastolic dysfunction where impairment in diastolic function occurs in the
      absence of concomitant reduction in systolic function. The phenomena which
      influence diastolic function, the clinical spectrum of diastolic dysfunction, the
      physiological perturbations which may serve as therapeutic targets for
      pharmacological therapy and recent therapeutic trials are reviewed.
      Recommendations regarding the therapeutic approach to the patient with diastolic
      dysfunction are summarised.

PMID- 11585016
TI  - Therapy of Graves' ophthalmopathy: a novel application of somatostatin analogues.

PMID- 11585017
TI  - Oral contraceptives and mood.
AB  - The past 40 years of research on the mood and behavioural effects of combined
      oral contraceptives (OCs) have yielded inconclusive results due to dramatic
      changes in the compounds and to methodological flaws inherent in studies
      undertaken to assess the effects of OCs. Since the late 1960s, the dosages of
      oestrogen and progestin in marketed OCs significantly declined and novel
      progestins were developed to deliver higher levels of progestogenic activity with
      a lower risk of adverse oestrogenic and androgenic effects. This review evaluates
      controlled, comparative studies that have focused on the efficaciousness of OCs
      as treatment for premenstrual syndrome (PMS) and those examining whether OCs may
      cause negative mood. It is suggested that the mood and behavioural effects of OCs
      might be attributed to different progestin compounds and possibly, their
      oestrogen ratios. There is a great need for more longitudinal, randomised,
      placebo-controlled studies to further clarify the mood and behavioural effects of
      OCs.

PMID- 11585018
TI  - Mifepristone: a potential postcoital contraceptive.
AB  - Mifepristone is an orally-active progesterone receptor antagonist. When a single
      dose of mifepristone is given in the mid- or late follicular phase, it may
      diminish or inhibit the luteinising hormone (LH) surge. In the early luteal
      phase, a single dose of mifepristone induces significant changes in the
      endometrium without affecting the hormonal levels or menstruation. When it is
      given in the mid-luteal phase, there will also be significant changes in the
      endometrium and some women may have two episodes of vaginal bleeding. A clinical
      trial suggests that a single dose of mifepristone in the early luteal phase may
      be an effective contraceptive agent but the lack of a cheap and easy method to
      identify the LH surge limits its clinical application. The administration of
      mifepristone alone or in combination with a prostaglandin does not appear to be
      an effective form of contraception. When used together with a prostaglandin, it
      may be an effective method for menstrual regulation but the cost and possible
      side effects of the prostaglandins limit its use. Mifepristone is a very
      effective method for emergency contraception. The incidence of side effects was
      also lower than that of the Yuzpe regimen. Lowering the dose of mifepristone from
      600 to 10 mg does not decrease its efficacy but the incidence of delay in onset
      of the subsequent menses is reduced. Despite its efficacy, the reputation of
      mifepristone as an abortion pill may limit its access in many countries.

PMID- 11585019
TI  - Male hormonal contraceptives.
AB  - As the world human population continues to explode, the need for effective, safe
      and convenient contraceptive methods escalates. Historically, women have borne
      the brunt of responsibility for contraception and family planning. Except for the
      condom, there are no easily reversible, male-based contraceptive options. Recent
      surveys have confirmed that the majority of men and women would consider using a
      hormonal male contraceptive if a safe, effective and convenient formulation were
      available. Investigators have sought to develop a male hormonal contraceptive
      based on the observation that spermatogenesis depends on stimulation by
      gonadotropins, follicle-stimulating hormone (FSH) and luteinising hormone (LH).
      Testosterone (T) and other hormones such as progestins suppress circulating
      gonadotropins and spermatogenesis and have been studied as potential male
      contraceptives. Results from two large, multi-centre trials demonstrated that
      high-dosage T conferred an overall contraceptive efficacy comparable to female
      oral contraceptives. This regimen was also fully reversible after
      discontinuation. However, this regimen was not universally effective and involved
      weekly im. injections that could be painful and inconvenient. In addition, the
      high dosage of T suppressed serum high-density lipoprotein (HDL) cholesterol
      levels, an effect that might increase atherogenesis. Investigators have attempted
      to develop a hormonal regimen that did not cause androgenic suppression of HDL
      cholesterol and that was uniformly effective by suppressing spermatogenesis to
      zero in all men. Studies of combination regimens of lower-dosage T and a
      progestin or a gonadotropin-releasing hormone analogue have demonstrated greater
      suppression of spermatogenesis than the WHO trials of high-dosage T but most of
      these regimens cause modest weight gain and suppression of serum HDL cholesterol
      levels. Overall, the data suggest that we are close to developing effective male
      hormonal contraceptives. The focus is now on developing effective oral regimens
      that could be safely taken daily or long-acting depot formulations of a male
      hormonal contraception that could be conveniently injected every 3 - 6 months. In
      this article, we shall review the exciting new developments in male hormonal
      contraception.

PMID- 11585020
TI  - Tamoxifen and the female reproductive tract.
AB  - The use of tamoxifen among women with breast cancer or at high risk of the
      disease has greatly expanded over the past several decades. Tamoxifen has a
      complex effect on the female reproductive tract and several tamoxifen-associated
      changes have been described among tamoxifen users. These include endometrial
      thickening, cervical and endometrial polyps, endometrial hyperplasia, endometrial
      adenocarcinoma, uterine sarcoma, increase in the size of uterine leiomyomata,
      exacerbation of endometriosis and ovarian cysts. The most common uterine change
      associated with tamoxifen is endometrial polyps. The annual incidence of
      endometrial cancer among women on tamoxifen is 2 per 1000 and seems to be related
      to the cumulative tamoxifen dose. It is not clear whether endometrial cancer
      occurring among women on tamoxifen is of worse prognosis than endometrial cancer
      occurring among women not receiving tamoxifen. Tamoxifen is associated with
      several sonographic changes which make the use of ultrasound in surveillance of
      these patients difficult. There is no indication to implement routine screening
      for endometrial cancer among all women on tamoxifen. However, endometrial biopsy,
      preferably via hysteroscopy, should be considered in women with uterine bleeding.

PMID- 11585021
TI  - Primary Sjogren's syndrome: oral aspects on pathogenesis, diagnostic criteria,
      clinical features and approaches for therapy.
AB  - Primary Sjogren's syndrome (pSS) is a chronic inflammatory systemic autoimmune
      disease affecting the exocrine glands and predominantly the salivary and lacrimal
      glands. The impaired gland function is assumed to be a result of progressive
      lymphocyte-mediated destruction of the exocrine gland tissue leading to the
      cardinal manifestations, hyposalivation and keratoconjunctivitis sicca (KCS), as
      well as devastating symptoms of oral and ocular dryness. Although primarily
      characterised as an exocrine dysfunction, non-exocrine organs may also be
      affected. The onset and course of pSS is usually insidious but may develop into a
      disabling disease, which profoundly affects the patient's general well being and
      quality of life. Moreover, pSS may even evolve into a lymphoid malignancy. The
      aetiology of pSS remains unknown but the pathogenesis of exocrine cell damage is
      apparently multi-factorial, including immunological, genetic, hormonal and viral
      components. Recent research also includes neurogenic aspects of exocrine gland
      dysfunction, including the interference of immune mediators with glandular
      response to neurotransmitters released from nerve fibres. pSS usually affects
      middle-aged women and the female:male ratio is 9:1. The prevalence varies from
      0.29-4.8%, depending on the population sampled and the diagnostic criteria used.
      At present, there are no specific diagnostic tests for pSS and no universally
      accepted diagnostic criteria. The current therapy is primarily symptomatic. This
      review focuses on the current oral clinical, diagnostic, pathogenic and
      therapeutic aspects of pSS.

PMID- 11585022
TI  - Recent developments in the management of haemophagocytic lymphohistiocytosis.
AB  - Over the past two decades, the underlying pathophysiology of haemophagocytic
      lymphohistiocytosis (HLH) (synonyms: haemophagocytic syndrome, macrophage
      activation syndrome) has been well recognised. Cytokine storm plays a major role,
      which derives from an inappropriate immune reaction caused by proliferating and
      activated T-cell or natural killer (NK) cells associated with macrophage
      activation and inadequate apoptosis of immunogenic cells. Many biological
      parameters reflecting activity of disease or response to treatment have been
      identified, in particular, serum ferritin has been confirmed to be one of the
      markers for HLH. The common types of HLH consist of non-hereditary (acquired)
      infection-associated disease such as Epstein-Barr virus (EBV)-haemophagocytic
      lymphohistiocytosis (HLH) and hereditary (familial) disease such as FHL, in
      which, at the molecular level, dysfunctional perforin was clarified. Regarding
      the therapeutic strategies, prompt differential diagnosis of underlying disease
      is essential and choice of treatment should be based on the risk (low or high) of
      prognosis, where either cyclosporin A, steroids or iv. immunoglobulin (IVIG) may
      be indicated as initial treatment for low-risk patients, with etoposide
      containing regimens for high-risk patients. Significant improvement of prognosis
      has been obtained by incorporating intensive supportive care at the disease onset
      and prompt introduction of immunosuppressants to control cytokine storm.
      Subsequent immunochemotherapy and haemopoietic stem cell transplantation have
      contributed significantly to further improve survival of hereditary and
      refractory HLH patients.

PMID- 11585023
TI  - Homocysteine-lowering treatment: an overview.
AB  - Elevated fasting plasma concentrations of homocysteine have a high prevalence in
      subjects with cardiovascular disease and have also been associated with an
      increased risk of atherothrombosis in most, but not all, prospective studies. The
      most frequent causes of hyperhomocysteinaemia are genetic defects, such as
      cystathionine-beta-synthase (CBS) deficiency, deficiencies of folic acid and/or
      vitamin B12, renal failure and interference in homocysteine metabolism by drugs
      or metabolic alterations. In most cases, no underlying cause can be established.
      Subjects with CBS deficiency are treated with pyridoxine with additional folic
      acid and betaine if necessary. Folic acid and vitamin B12 deficiencies should be
      corrected by supplementation. Increases in folate intake by dietary changes or
      fortification can also lower plasma homocysteine in vitamin-replete subjects with
      normal plasma homocysteine levels. In renal failure, folic acid treatment (1-5
      mg/day) ameliorates the plasma homocysteine level in most cases but
      hyperhomocysteinaemia persists in the majority of patients. Primary (fasting)
      hyperhomocysteinaemia can be treated with folic acid (0.5-5 mg/day). An abnormal
      methionine-loading test identifies additional patients at risk and postmethionine
      loading hyperhomocysteinaemia should be treated with a combination of pyridoxine
      and folic acid. In the absence of dose-effect studies, a combination of
      pyridoxine (50 mg) and folic acid (5 mg) is advised. Large clinical trials are
      currently underway to establish the role of homocysteine-lowering therapy in the
      secondary prevention of atherothrombotic disease. In view of the effective, cheap
      and safe character of therapy with folic acid and pyridoxine, a policy can be
      accepted to screen and treat high-risk patients until these trials have been
      concluded.

PMID- 11585024
TI  - Update on alendronate for osteoporosis: once-weekly dosing.
AB  - Alendronate (Fosamax, Merck & Co.) is now available in a 70 mg formulation to be
      taken once a week for osteoporosis. Earlier studies demonstrated that alendronate
      is highly effective for increasing bone density, reducing bone turnover rate and
      reducing the risk of fractures. A subsequent clinical trial reported that the
      once-weekly dosing regimen is therapeutically equivalent to the daily regimen.
      Administering alendronate (70 mg) once a week effectively provides continuous
      inhibition of bone resorption because bone resorption by osteoclasts is a slow
      process that typically requires 2-3 weeks for completion and alendronate remains
      at active bone remodelling sites for a sustained period and (when present in
      sufficient concentration) effectively inhibits bone resorption. Bisphosphonates
      are currently the pre-eminent therapy for osteoporosis. Once-weekly alendronate
      represents a major advance in convenience because oral bisphosphonates must be
      taken in the fasting state with water at least 30 minutes before consuming food
      or beverages. Sales data several months after introduction of once-weekly
      alendronate into the marketplace demonstrate rapid and extensive acceptance of
      this new regimen.

PMID- 11585025
TI  - Zinc acetate for the treatment of Wilson's disease.
AB  - Zinc acetate (Galzin, Gate Pharmaceutical Co.) has been developed for the
      treatment of Wilson's disease, an inherited disease of copper accumulation and
      copper toxicity in brain and liver. Zinc acetate has been approved by the US FDA
      for maintenance therapy of adult and paediatric Wilson's disease patients but
      also has efficacy in the treatment of pregnant patients and presymptomatic
      patients from the beginning. It also has value as adjunctive therapy for the
      initial treatment of symptomatic patients. Zinc's mechanism of action involves
      induction of intestinal cell metallothionein (Mt), which blocks copper absorption
      from the intestinal track. A negative copper balance is caused by blockade not
      only of absorption of food copper but the blockade of reabsorption of the
      considerable amount of endogenously secreted copper in saliva, gastric juice and
      intestinal secretions. Zinc is completely effective in controlling copper levels
      and toxicity in Wilson's disease, as are other anticopper agents. Zinc's major
      advantage over other anticopper agents is its extremely low level of toxicity.
      The only side effect is some degree of initial gastric irritation in
      approximately10% of patients, which usually decreases and becomes insignificant
      over time. As with all long-term therapies, compliance is a problem in some
      patients and dictates regular monitoring with 24 h urine copper and zinc
      measurements. As with all anticopper therapies, over a long period of time,
      overtreatment and induction of copper deficiency can occur. This is to be avoided
      particularly in children because copper is required for growth.

PMID- 11585026
TI  - Calfactant.
AB  - Surfactant administration has proven remarkably effective in the prevention and
      treatment of infantile respiratory distress syndrome (IRDS) and may also be
      beneficial in other forms of acute lung injury. Several surfactant products are
      available commercially along with others in various phases of development and
      clinical trials. While all of these products share an ability to lower surface
      tension in vitro, there are substantial compositional differences that appear to
      affect their in vivo efficacy. At present, the 'modified natural' surfactants
      containing the hydrophobic surfactant proteins SP-B and SP-C appear most
      effective. Calfactant may have a particular advantage because of its relatively
      high content of SP-B and its lack of contamination with non-surfactant lipids and
      proteins.

PMID- 11585027
TI  - Oral uracil-tegafur: an alternative to intravenous 5-fluorouracil?
AB  - The fluoropyrimidines have been used in the treatment of a number of tumour types
      over the past 40 years. Particular attention has focused on the use of 5
      fluorouracil (5-FU) in colorectal cancer for which, until recently, there has
      been a lack of other effective chemotherapy. In an attempt to optimise the
      efficacy of fluoropyrimidines, a number of approaches have been used. These
      include alternative methods of iv. scheduling, the use of co-factors and the
      development of oral compounds. The aim of oral agents is to satisfy patient
      preference while maintaining the efficacy of sustained drug exposure seen with
      prolonged or continuous infusions of iv. 5-FU. One such oral compound is uracil
      tegafur (UFT), which combines tegafur (ftorafur, a 5-FU prodrug) and uracil in a
      1:4 molar ratio. UFT first entered Phase I trials in Japan over 20 years ago but
      has only recently received significant exposure in Phase II and III trials.
      Results from a number of Phase III studies in Europe and in the US are now
      becoming available. With UFT recently approved for colorectal cancer in many
      European countries, although not in the US, it is timely to review the current
      situation and future prospects for this agent.

PMID- 11585028
TI  - ReoPro rules: results from the 'Do Tirofiban and ReoPro Give Similar Efficacy
      Trial' (TARGET).
AB  - In the treatment of atherosclerotic disease, stenting in the presence of a
      glycoprotein (GP) IIb/IIIa antagonist is becoming an increasingly common
      procedure. The 'Do Tirofiban and ReoPro Give Similar Efficacy Trial' (TARGET) was
      designed to determine whether the cheaper tirofiban was as effective and safe as
      abciximab in the prevention of ischaemic events with stenting. Unexpectedly,
      abciximab was shown to be superior to tirofiban. Tirofiban is a selective GP
      IIb/IIIa antagonist whereas abciximab has additional anti-inflammatory actions,
      which may contribute to its superiority.

PMID- 11585029
TI  - Analysis of monophasic and biphasic electrical stimulation of  nerve.
AB  - In an earlier study, biphasic and monphasic electrical stimulation of the
      auditory nerve was performed in cats with a cochlear implant. Single-unit
      recordings demonstrated that spikes resulting from monophasic and biphasic
      stimuli have different thresholds and latencies. Monophasic thresholds are lower
      and latencies are shorter under cathodic stimulation. Results from stochastic
      simulations of a biophysical model of electrical stimulation are similar. A
      simple analysis of a linear, "integrate to threshold" membrane model accounts for
      the threshold and latency differences observed experimentally and
      computationally. Since biphasic stimuli are used extensively in functional
      electrical stimulation, this analysis greatly simplifies the biophysical
      interpretation of responses to clinically relevant stimuli by relating them to
      the responses obtained with monophasic stimuli.

PMID- 11585030
TI  - Analysis of galvanic skin responses with principal components and clustering
      techniques.
AB  - An advanced method for analyzing the patterning of successive galvanic skin
      responses (GSR) is presented. The proposed method is based on principal component
      analysis in which the vector containing the measured signal is presented as a
      weighted sum of orthogonal basis vectors. The method is tested using measurements
      from 20 healthy controls and 13 psychotic patients. For each subject, 11
      surprising auditory stimuli were delivered to right ear at irregular intervals
      and evoked GSRs were recorded from the hand. For most of the healthy controls,
      there was a clear pattern in successive GSRs, whereas within psychotic patients
      the lack of time-locking of GSRs seemed to be characteristical. These between
      group differences can be revealed by the proposed method. With application to
      clustering a significant discrimination, with overall correct ratings of 82%, of
      healthy controls and psychotic patients is achieved. A significant fact is that
      all patients were ranked correctly giving the proposed method a sensitivity of
      100%.

PMID- 11585031
TI  - A multiresolution framework to MEG/EEG source imaging.
AB  - A new method based on a multiresolution approach for solving the ill-posed
      problem of brain electrical activity reconstruction from electroencephaloram
      (EEG)/magnetoencephalogram (MEG) signals is proposed in a distributed source
      model. At each step of the algorithm, a regularized solution to the inverse
      problem is used to constrain the source space on the cortical surface to be
      scanned at higher spatial resolution. We present the iterative procedure together
      with an extension of the ST-maximum a posteriori method [1] that integrates
      spatial and temporal a priori information in an estimator of the brain electrical
      activity. Results from EEG in a phantom head experiment with a real human skull
      and from real MEG data on a healthy human subject are presented. The performances
      of the multiresolution method combined with a nonquadratic estimator are compared
      with commonly used dipolar methods, and to minimum-norm method with and without
      multiresolution. In all cases, the proposed approach proved to be more efficient
      both in terms of computational load and result quality, for the identification of
      sparse focal patterns of cortical current density, than the fixed scale imaging
      approach.

PMID- 11585032
TI  - Artificial neural networks for discriminating pathologic from normal peripheral
      vascular tissue.
AB  - The identification of the state of human peripheral vascular tissue by using
      artificial neural networks is discussed in this paper. Two different laser
      emission lines (He-Cd, Ar+) are used to excite the chromophores of tissue
      samples. The fluorescence spectrum obtained, is passed through a nonlinear filter
      based on a high-order (HO) neural network neural network (NN) [HONN] whose
      weights are updated by stable learning laws, to perform feature extraction. The
      values of the feature vector reveal information regarding the tissue state. Then
      a classical multilayer perceptron is employed to serve as a classifier of the
      feature vector, giving 100% successful results for the specific data set
      considered. Our method achieves not only the discrimination between normal and
      pathologic human tissue, but also the successful discrimination between the
      different types of pathologic tissue (fibrous, calcified). Furthermore, the small
      time needed to acquire and analyze the fluorescence spectra together with the
      high rates of success, proves our method very attractive for real-time
      applications.

PMID- 11585033
TI  - Quantifying spatial localization of optical mapping using Monte Carlo
      simulations.
AB  - Optical mapping techniques used to study spatial distributions of cardiac
      activity can be divided into two categories. 1) Broad-field excitation method, in
      which hearts stained with voltage or calcium sensitive dyes are illuminated with
      broad-field excitation light and fluorescence is collected by image or photodiode
      arrays. 2) Laser scanning method, in which illumination uses a scanning laser and
      fluorescence is collected with a photomultiplier tube. The spatial localization
      of the fluorescence signal for these two methods is unknown and may depend upon
      light absorption and scattering at both excitation and emission wavelengths. We
      measured the absorption coefficients (micro a), scattering coefficients (micro
      s), and scattering anisotropy coefficients (g) at representative excitation and
      emission wavelengths in rabbit heart tissue stained with di-4-ANEPPS or co
      stained with both Rh237 and Oregon Green 488 BAPTA 1. Monte Carlo models were
      then used to simulate absorption and scattering of excitation light and
      fluorescence emission light for both broad-field and laser methods in three
      dimensional tissue. Contributions of local emissions throughout the tissue to
      fluorescence collected from the tissue surface were determined for both methods.
      Our results show that spatial localization depends on the light absorption and
      scattering in tissue and on the optical mapping method that is used. A tissue
      region larger than the laser beam or collecting area of the array element
      contributes to the optical recordings.

PMID- 11585034
TI  - Inhomogeneity of action potential waveshape assists frequency entrainment of
      cardiac pacemaker cells.
AB  - In this paper, we have employed ionic models of sinoatrial node cells to
      investigate the synchronization of a pair of coupled cardiac pacemaker cells from
      central and peripheral regions of the sinoatrial node. The free-running cycle
      length of the cell models was perturbed using two independent techniques and the
      minimum coupling conductance required to achieve frequency entrainment was used
      to assess the relative ease with which various cell pairs achieve entrainment.
      The factors effecting entrainment were further investigated using single-cell
      models paced with an artificial biphasic coupling current. Our simulation results
      suggest that dissimilar cell types, those with largely different upstroke
      velocities entrain more easily, that is, they require less coupling conductance
      to achieve 1:1 frequency entrainment. We, therefore, propose that regional
      variation in action-potential waveshape within the sinoatrial node assists
      frequency synchronization in vivo.

PMID- 11585035
TI  - A new algorithm for linear and nonlinear ARMA model parameter estimation using
      affine geometry.
AB  - A linear and nonlinear autoregressive (AR) moving average (MA) (ARMA)
      identification algorithm is developed for modeling time series data. The new
      algorithm is based on the concepts of affine geometry in which the salient
      feature of the algorithm is to remove the linearly dependent ARMA vectors from
      the pool of candidate ARMA vectors. For noiseless time series data with a priori
      incorrect model-order selection, computer simulations show that accurate linear
      and nonlinear ARMA model parameters can be obtained with the new algorithm. Many
      algorithms, including the fast orthogonal search (FOS) algorithm, are not able to
      obtain correct parameter estimates in every case, even with noiseless time series
      data, because their model-order search criteria are suboptimal. For data
      contaminated with noise, computer simulations show that the new algorithm
      performs better than the FOS algorithm for MA processes, and similarly to the FOS
      algorithm for ARMA processes. However, the computational time to obtain the
      parameter estimates with the new algorithm is faster than with FOS. Application
      of the new algorithm to experimentally obtained renal blood flow and pressure
      data show that the new algorithm is reliable in obtaining physiologically
      understandable transfer function relations between blood pressure and flow
      signals.

PMID- 11585036
TI  - Computer-assisted transurethral laser resection of the prostate (CALRP):
      theoretical and experimental motion plan.
AB  - Computer-Assisted transurethral laser resection of the prostate (CALRP) is a
      treatment modality that was designed and developed based on an integrated system
      of computer, robotics and laser technology in association with a minimally
      invasive surgery known as laser transurethral resection of the prostate (LRP).
      CALRP possesses complementary capabilities that could remedy many of the problems
      faced by surgeons in conventional LRP by delivering a treatment with
      repeatability and reliability. The work deals primarily in determining the
      feasibility study of the computer-assisted lasing motion plan (planned motion
      sequence controlled by a program) for LRP. A theoretical motion plan that
      analyzes numerically the lasing motion of the fiber was designed by calculating
      the profile removal rate and in vitro experiments conducted on human cadaveric
      prostate to verify and validate the designed motion plan. The novel motion plan,
      which was executed experimentally using the LaserTrode lightguide, accomplished
      the objective of resecting the enlarged prostate with the aid of computer and
      robotics technology.

PMID- 11585037
TI  - Development of a time-cycled volume-controlled pressure-limited respirator and
      lung mechanics system for total liquid ventilation.
AB  - Total liquid ventilation can support gas exchange in animal models of lung
      injury. Clinical application awaits further technical improvements and
      performance verification. Our aim was to develop a liquid ventilator, able to
      deliver accurate tidal volumes, and a computerized system for measuring lung
      mechanics. The computer-assisted, piston-driven respirator controlled ventilatory
      parameters that were displayed and modified on a real-time basis. Pressure and
      temperature transducers along with a lineal displacement controller provided the
      necessary signals to calculate lung mechanics. Ten newborn lambs (<6 days old)
      with respiratory failure induced by lung lavage, were monitored using the system.
      Electromechanical, hydraulic, and data acquisition/analysis components of the
      ventilator were developed and tested in animals with respiratory failure. All
      pulmonary signals were collected synchronized in time, displayed in real-time,
      and archived on digital media. The total mean error (due to transducers, analog
      to-digital conversion, amplifiers, etc.) was less than 5% compared with
      calibrated signals. Components (tubing, pistons, etc.) in contact with exchange
      fluids were developed so that they could be readily switched, a feature that will
      be important in clinical settings. Improvements in gas exchange and lung
      mechanics were observed during liquid ventilation, without impairment of
      cardiovascular profiles. The total liquid ventilator maintained accurate control
      of tidal volumes and the sequencing of inspiration/expiration. The computerized
      system demonstrated its ability to monitor in vivo lung mechanics, providing
      valuable data for early decision making.

PMID- 11585038
TI  - Hepatic bipolar radio-frequency ablation between separated multiprong electrodes.
AB  - Radio-frequency (RF) ablation has become an important means of treatment of
      nonresectable primary and metastatic liver tumors. Major limitations are small
      lesion size, which make multiple applications necessary, and incomplete killing
      of tumor cells, resulting in high recurrence rates. We examined a new bipolar RF
      ablation method incorporating two probes with hooked electrodes (RITA model 30).
      We performed monopolar and bipolar in vivo experiments on three pigs. The
      electrodes were 2.5 cm apart and rotated 45 degrees relative to each other. We
      used temperature-controlled mode at 95 degrees C. Lesion volumes were 3.9+/-1.8
      cm3 (n=7) for the monopolar case and 12.2 +/- 3 cm3 (n=10) for the bipolar case.
      We generated finite-element models (FEMs) of monopolar and bipolar
      configurations. We analyzed the distribution of temperature and electric field of
      the finite element model. The lesion volumes for the FEM are 7.95 cm3 for the
      monopolar and 18.79 cm3 for the bipolar case. The new bipolar method creates
      larger lesions and is less dependent on local inhomogenities in liver tissue-such
      as blood perfusion-compared with monopolar RF ablation. A limitation of the new
      method is that the power dissipation of the two probes cannot be controlled
      independently in response to different conditions in the vicinity of each probe.
      This may result in nonuniform lesions and decreased lesion size.

PMID- 11585039
TI  - Balance prosthesis based on micromechanical sensors using vibrotactile feedback
      of tilt.
AB  - A prototype balance prosthesis has been made using miniature, high-performance
      inertial sensors to measure lateral head tilt and vibrotactile elements mounted
      on the body to display head tilt to the user. The device has been used to study
      the feasibility of providing artificial feedback of head tilt to reduce postural
      sway during quiet standing using six healthy subjects. Two vibrotactile display
      schemes were used: one in which the individual vibrating elements, called
      tactors, were placed on the shoulders (shoulder tactors); another in which
      columns of tactors were placed on the right and left sides of the trunk (side
      tactors). Root-mean-square head-tilt angle (Tilt) and center of pressure
      displacement (Sway) were measured for normal subjects standing in a semi-tandem
      Romberg position with eyes closed, under four conditions: no balance aids;
      shoulder tactors; side tactors; and light touch. Compared with no balance aids,
      the side tactors significantly reduced Tilt (35%) and Sway (33%). Shoulder
      tactors also significantly reduced Tilt (44%) and Sway (17%). Compared with
      tactors, light touch resulted in less Sway, but more Tilt. The results suggest
      that healthy normal subjects can reduce their lateral postural sway using head
      tilt information as provided by a vibrotactile display. Thus, further testing
      with balance-impaired subjects is now warranted.

PMID- 11585040
TI  - A 3-D differential coil design for localized magnetic stimulation.
AB  - A novel three-dimensional (3-D) differential coil has been designed for improving
      the localization of magnetic stimulation. This new coil design consists of a
      butterfly coil with two additional wing units and an extra bottom unit, both
      perpendicular to the plane of the butterfly coil. The wing units produce opposite
      fields to restrict the spread of induced fields while the bottom unit enhances
      the induced fields at the excitation site. The peak induced field generated by
      this new design is located at the center of the coil, providing an easy
      identification of the excitation site. The field localization of the new coil is
      comparable with that of much smaller coils but with an inductance compatible to
      current magnetic stimulators. Numerical computations based on the principles of
      electromagnetic induction and using a human nerve model were performed to analyze
      the induced fields and the stimulation thresholds of new coil designs. The
      localization of the coil design was assessed by a half power region (HPR), within
      which the magnitude of the normalized induced field is greater than 1/square root
      of 2. The HPR for a 3-D differential coil built is improved (decreased) by a
      factor of three compared with a standard butterfly coil. Induced fields by this
      new coil were measured and in agreement with theoretical calculations.

PMID- 11585041
TI  - Parametric dependence of SAR on permittivity values in a man model.
AB  - The development and widespread use of advanced three-dimensional digital
      anatomical models to calculate specific absorption rate (SAR) values in
      biological material has resulted in the need to understand how model parameters
      (e.g., permittivity value) affect the predicted whole-body and localized SAR
      values. The application of the man dosimetry model requires that permittivity
      values (dielectric value and conductivity) be allocated to the various tissues at
      all the frequencies to which the model will be exposed. In the 3-mm-resolution
      man model, the permittivity values for all 39 tissue-types were altered
      simultaneously for each orientation and applied frequency. In addition,
      permittivity values for muscle, fat, skin, and bone marrow were manipulated
      independently. The finite-difference time-domain code was used to predict
      localized and whole-body normalized SAR values. The model was processed in the
      far-field conditions at the resonant frequency (70 MHz) and above (200, 400, 918,
      and 2060 MHz) for E orientation. In addition, other orientations (K, H) of the
      model to the incident fields were used where no substantial resonant frequency
      exists. Variability in permittivity values did not substantially influence whole
      body SAR values, while localized SAR values for individual tissues were
      substantially affected by these changes. Changes in permittivity had greatest
      effect on localized SAR values when they were low compare to the whole-body SAR
      value or when errors involved tissues that represent a substantial proportion of
      the body mass (i.e., muscle). Furthermore, we establish the partial derivative of
      whole-body and localized SAR values with respect to the dielectric value and
      conductivity for muscle independently. It was shown that uncertainties in
      dielectric value or conductivity do not substantially influence normalized whole
      body SAR. Detailed investigation on localized SAR ratios showed that conductivity
      presents a more substantial factor in absorption of energy in tissues than
      dielectric value for almost all applied exposure conditions.

PMID- 11585042
TI  - Improving the homogeneity of the magnetic field in the magnetic search coil
      technique.
AB  - The magnetic search coil technique is used to obtain accurate eye-movement
      measurements. For the data analysis it must be assumed that the magnetic field
      does not change over time (apart from the required modulation). To comply with
      this assumption either no translational movements of the eye coil(s) are allowed
      or the magnetic field has to be perfectly homogeneous. Both are normally not the
      case, i.e., measurement errors occur. These errors can be minimized by keeping
      the magnetic field as homogeneous as possible. Larger field coils are typically
      chosen to achieve this aim. However, sometimes the experimental setup imposes
      limitations on the size of the configuration. We present a method for improving
      the homogeneity of the magnetic field by adding supplementary field coils without
      changing the size of the configuration.

PMID- 11585043
TI  - Bayesian approach to segmentation of statistical parametric maps.
AB  - A contextual segmentation technique to detect brain activation from functional
      brain images is presented in the Bayesian framework. Unlike earlier similar
      approaches [Holmes and Ford (1993) and Descombes et al. (1998)], a Markov random
      field (MRF) is used to represent configurations of activated brain voxels, and
      likelihoods given by statistical parametric maps (SPM's) are directly used to
      find the maximum a posteriori (MAP) estimation of segmentation. The iterative
      segmentation algorithm, which is based on a simulated annealing scheme, is fully
      data-driven and capable of analyzing experiments involving multiple-input
      stimuli. Simulation results and comparisons with the simple thresholding and the
      statistical parametric mapping (SPM) approaches are presented with synthetic
      images, and functional MR images acquired in memory retrieval and event-related
      working memory tasks. The experiments show that an MRF is a valid representation
      of the activation patterns obtained in functional brain images, and the present
      technique renders a superior segmentation scheme to the context-free approach and
      the SPM approach.

PMID- 11585044
TI  - A new 3-D display method for 12-lead ECG.
AB  - A new three-dimensional (3-D) 12-lead electrocardiogram (ECG) display method is
      presented which employs a 3-D rectangular coordinate system to display the 12
      lead cardiac electric signals in two 3-D graphs. The 3-D graph consists of a
      temporal axis representing the time domain of the cardiac signals, a spatial axis
      representing the lead positions, and an amplitude axis representing the voltages
      of the cardiac signals. The six horizontal plane leads and the other six frontal
      plane leads were displayed in two 3-D graphs, respectively. The voltages of the
      cardiac signals were represented in rainbow-like colors. Cubic interpolation was
      employed to insert interconnecting points between neighboring leads on each plane
      and to smooth the surface of the 3-D ECG graphs. The 3-D ECG graphs of a normal
      subject, a patient with myocardial infarction, and a patient with left bundle
      branch block were presented in this paper. This new display method could not only
      be used as a complementary display method to the 12-lead ECG, but also provide
      physicians with an overall integral view about the spatial distribution of the
      cardiac signals.

PMID- 11585045
TI  - Multichannel ECG compression using multichannel adaptive vector quantization.
AB  - Adaptive vector quantization (AVQ) is a recently proposed approach for
      electrocardiogram (ECG) compression. The adaptability of the approach can be used
      to control the quality of reconstructed signals. However, like most of other ECG
      compression methods, AVQ only deals with the single-channel ECG, and for the
      multichannel (MC) ECG, coding ECG signals on a channel by channel basis is not
      efficient, because the correlation across channels is not exploited. To exploit
      this correlation, an MC version of AVQ is proposed. In the proposed approach, the
      AVQ index from each channel is collected to form a new input vector. The vector
      is then vector quantized adaptively using one additional codebook called index
      codebook. Both the MIT/BIH database and a clinical Holter database are tested.
      The experimental results show that, for exactly the same quality of reconstructed
      signals, the MC-AVQ performs better than single-channel AVQ in terms of bit rate.
      A theoretical analysis supporting this result is also demonstrated in this paper.
      For the same and relatively good visual quality, the average compressed data
      rate/channel is reduced from 293.5 b/s using the single-channel AVQ to 238.2 b/s
      using the MC-AVQ in the MIT/BIH case.

PMID- 11585046
TI  - The effect of plunge electrodes during electrical stimulation of cardiac tissue.
AB  - The mechanism for far-field stimulation of cardiac tissue is not known, although
      many hypotheses have been suggested. This paper explores a new hypothesis: the
      insulated plunge electrodes used in experiments to map the extracellular
      potential may affect the transmembrane potential when an electric field is
      applied to cardiac tissue. Our calculation simulates a 10-mm-diameter sheet of
      passive tissue with a circular insulated plunge electrode in the middle of it,
      ranging in diameter from 0.05 to 2 mm. We calculate the transmembrane potential
      induced by a 500-V/m electric field. Our results show that a transmembrane
      potential is induced around the electrode in alternating areas of depolarization
      and hyperpolarization. If the electric field is oriented parallel to the
      myocardial fibers, the maximum transmembrane potential is 89 mV. A layer of fluid
      around the electrode increases the transmembrane potential. We conclude that
      plunge electrodes may introduce artifacts during experiments designed to study
      the response of the heart to strong electric shocks.

PMID- 11585047
TI  - A statistical technique for measuring synchronism between cortical regions in the
      EEG during rhythmic stimulation.
AB  - The coherence function has been widely applied in quantifying the degree of
      synchronism between electroencephalogram (EEG) signals obtained from different
      brain regions. However, when applied to investigating synchronization resulting
      from rhythmic stimulation, misleading results can arise from the high correlation
      of background EEG activity. We, thus propose a modified measure, which emphasizes
      the synchronized stimulus responses and reduces the influence of the spontaneous
      EEG activity. Critical values for this estimator are derived and tested in Monte
      Carlo simulations. The effectiveness of the method is illustrated on data
      recorded from 12 young normal subjects during rhythmic photic stimulation.

PMID- 11585048
TI  - Fatty acid amide hydrolase: biochemistry, pharmacology, and therapeutic
      possibilities for an enzyme hydrolyzing anandamide, 2-arachidonoylglycerol,
      palmitoylethanolamide, and oleamide.
AB  - Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of a number
      of important endogenous fatty acid amides, including the endogenous
      cannabimimetic agent anandamide (AEA), the sleep-inducing compound oleamide, and
      the putative anti-inflammatory agent palmitoylethanolamide (PEA). In recent
      years, there have been great advances in our understanding of the biochemical and
      pharmacological properties of the enzyme. In this commentary, the structure and
      biochemical properties of FAAH and the development of potent and selective FAAH
      inhibitors are reviewed, together with a brief discussion on the therapeutic
      possibilities for such compounds in the treatment of inflammatory pain and
      ischaemic states.

PMID- 11585049
TI  - Effects of (-)-epigallocatechin-3-gallate, the main component of green tea, on
      the cloned rat brain Kv1.5 potassium channels.
AB  - The interaction of (-)-epigallocatechin-3-gallate (EGCG), the main component of
      green tea (Camellia sinensis), with rat brain Kv1.5 channels (rKv1.5) stably
      expressed in Chinese hamster ovary (CHO) cells was investigated using the whole
      cell patch-clamp technique. EGCG inhibited rKv1.5 currents at +50 mV in a
      concentration-dependent manner, with an IC50 of 101.2+/-6.2 microM. Pretreatment
      with protein tyrosine kinase (PTK) inhibitors (10 microM genistein, 100 microM
      AG1296), a tyrosine phosphatase inhibitor (500 microM sodium orthovanadate), or a
      protein kinase C (PKC) inhibitor (10 microM chelerythrine) did not block the
      inhibitory effect of EGCG on rKv1.5. The inhibition of rKv1.5 by EGCG displayed
      voltage-independence over the full activation voltage range positive to +10 mV.
      EGCG had no effect on the midpoint potential or the slope factor for steady-state
      activation and inactivation. EGCG did not affect the ion selectivity of rKv1.5.
      The activation (at +50 mV) kinetics was significantly slowed by EGCG. During
      repolarization (at -40 mV), EGCG also slowed the deactivation of the tail
      currents, resulting in a crossover phenomenon. Reversal of inhibition was
      detected by the application of repetitive depolarizing pulses and of identical
      double pulses, especially during the early part of the activating pulse, in the
      presence of EGCG. EGCG-induced inhibition of rKv1.5 showed identical affinity
      between EGCG and the multiple closed states of rKv1.5. These results suggest that
      EGCG interacts directly with rKv1.5 channels. Furthermore, by analyzing the
      kinetics of the interaction between EGCG and rKv1.5, we conclude that the
      inhibition of rKv1.5 channels by EGCG includes at least two effects: EGCG
      preferentially binds to the channel in the closed state, and blocks the channel
      by pore occlusion while depolarization is maintained.

PMID- 11585050
TI  - Regulation of agonist binding to rat ET(B) receptors by cations and GTPgammaS.
AB  - Endothelins exert their physiological effects through interaction with cell
      surface receptors that are members of the G-protein-coupled receptor family. The
      endothelin receptor subtype B (ET(B) receptor) is abundantly expressed in rat
      cerebellum. Since agonist binding to G-protein-coupled receptors may be modulated
      by cations and guanine nucleotides, we investigated the effects of cations and
      guanosine 5'-O-(2-thiotriphosphate) (GTPgammaS) on 125I-endothelin-1 (125I-ET-1)
      binding to rat cerebellar membranes. Both Na+ and Mg2+-stimulated 125I-ET-1
      binding causing an increase in receptor affinity for the agonist. While the
      effect of the divalent cation was evident at relatively low concentrations (5-10
      mM), the stimulatory activity of the monovalent cation appeared at relatively
      high concentrations (50 mM). Additive activities of 25-50 mM NaCl and 1 mM MgCl2
      suggested that monovalent and divalent cations increased receptor affinity for ET
      1 by different mechanisms. In the presence of 5 mM MgCl2, 50 mM NaCl caused an
      additional modest reduction of the Kd value. Whereas 5 mM MgCl2 affected the
      displacement curves of both ET-3 and suc-[Glu9, Ala11,15]-endothelin-1 (8-21)
      (IRL 1620), the influence of 50 mM NaCl on these curves was less substantial. All
      together, these results suggest that modulation of receptor affinity by NaCl
      depends on the nature of the displacing agonist. In the presence of 5 mM MgCl2 or
      50 mM NaCl, a partial regulation of 125I-ET-1 binding by GTPgammaS was
      detectable, while in the absence of cations no GTPgammaS-dependent inhibition was
      evident.

PMID- 11585051
TI  - Shortcuts in genome-scale cancer pharmacology research from multivariate analysis
      of the National Cancer Institute gene expression database.
AB  - Application of a soft multivariate statistical procedure, called PLS, partial
      least squares modelling in latent variables or projections to latent structures,
      allows extensive exploitation of the enormous amount of information embedded in
      the National Cancer Institute gene expression and antitumour screen databases.
      Interpretation of the statistical results provides new significant biological
      insights such as classification of human tumour cell lines based on their gene
      expression patterns, evaluation of the influence of gene transcripts on drug
      efficacy and assessment of their selectivity for classes of compounds which act
      by the same mechanism, and identification of uncharacterized gene expression
      targets involved in cancer chemotherapy. Among them, the transcripts GC11121,
      GC17689, and GC18564 (unknown gene products extremely selective for RNA/DNA
      antimetabolites) are indicated by the present work as deserving high priority in
      future molecular studies.

PMID- 11585052
TI  - Potential application of plant lipid transfer proteins for drug delivery.
AB  - Ligand-binding proteins show an increasing interest as drug carriers and delivery
      systems [Wolf FA, Brett GM. Pharmacol Rev, 1000;52:207-36]. The wide binding
      properties of plant non-specific lipid transfer proteins such as LTP1 also offer
      many unexplored possibilities for such a task. In the present paper, by using
      intrinsic tyrosine LTP1 fluorescence, we survey, for the first time, the binding
      of wheat LTP1 with various ligands having cosmetic or pharmaceutical
      applications. LTP1 was found to bind skin lipids such as sphingosine,
      sphingomyelin, and cerebroside with an affinity of about one micromolar, low
      enough to allow a slow release of these molecules. Ether phospholipids and an
      azole derivative BD56 having antitumoral and/or antileishmania properties were
      also shown to bind LTP1 with similar affinity. Finally, amphotericin B, which is
      widely used as an antifungal drug, was shown to form a complex with LTP1,
      although no affinity could be determined. This binding study is a prerequisite
      for further work aimed at developing applications in LTP-mediated transport and
      controlled release of low molecular weight drugs.

PMID- 11585053
TI  - The absence of stereoselective P-glycoprotein- and multidrug resistance
      associated protein-mediated transport of daunorubicin.
AB  - Multidrug resistance phenotype in mammalian cells is often correlated with
      overexpression of P-glycoprotein (P-gp) or multidrug resistance-associated
      protein (MRP1). Both proteins are energy-dependent drug efflux pumps that
      efficiently reduce the intracellular accumulation and hence the cytotoxicity of
      many natural cytotoxins. Thus, both P-gp and MRP1 proteins are able to transport
      anthracycline but the role of chirality has not, up to now, been addressed. In
      this study, we compared the P-gp- and MRP1-mediated efflux of daunorubicin and
      its enantiomer WP900 in multidrug-resistant cells overexpressing either P-gp
      (K562/ADR cells) or MRP1 (GLC4/ADR cells). Using fluorescence techniques, we
      showed that in both cell lines the presence of the pump yielded a gradient of
      drug concentration: the intracellular free drug concentration in the cytosol was
      lower than the extracellular free drug concentration. Our data showed that the
      gradient of concentration generated by the pump was the same whether DNR or WP900
      was used. This means that P-gp on the one hand and MRP1 on the other recognise
      WP900 as well as DNR and that the chirality of the molecule plays no role.

PMID- 11585054
TI  - Enhanced activity of antisense phosphorothioate oligos against leishmania
      amastigotes: augmented uptake of oligo, ribonuclease H activation, and efficient
      target intervention under altered growth conditions.
AB  - Leishmania, a parasitic protozoan, infects human macrophages, often causing
      severe morbidity and mortality. The pathogenic form of this parasite, the
      amastigote, lives inside the acidic phagolysosomes of infected macrophages. In
      our attempt to develop anti-miniexon phosphorothioate oligodeoxyribonucleotides
      (S-oligos) as an alternative chemotherapy against Leishmania, we found that
      intracellular as well as 'axenic' amastigotes were more susceptible to these S
      oligos than were the cultured promastigotes. Lower pH (4.5) and elevated
      temperature (35 degrees) of the medium were among the direct enhancing factors
      for killing. Addition of the cationic polypeptide poly-l-lysine (PLL) to the
      growth medium further enhanced the killing effect of the S-oligo at pH 4.5. The
      enhancement of specific ablation of mRNA expression was directly correlated to
      the increased leishmanicidal activity of the S-oligo. This was shown by the
      increased inhibition of luciferase activity expressed in transgenic Leishmania
      amazonensis promastigotes by anti-miniexon S-oligo or anti-luciferase S-oligo at
      acidic pHs and in the presence of PLL. The leishmanicidal effects of S-oligos at
      acidic pH and in the presence of PLL were related to increased uptake of the S
      oligos under these conditions. The rate of S-oligo uptake was enhanced up to 15
      fold at pH 4.5. The addition of PLL to the assay medium at acidic pH further
      enhanced the uptake of S-oligo up to 80-fold. RNase H is known to accentuate the
      antisense action of S-oligos. We found that at an elevated temperature RNase H
      activity in Leishmania cell extracts increased about 5-fold. Thus, enhanced
      uptake of S-oligos at the acidic pH of macrophage phagolysosomes and activation
      of RNase H may explain the efficient killing of the parasite in macrophages, both
      in tissue culture and in the animal model, by antisense miniexon
      oligonucleotide/PLL, when targeted directly to the parasite-containing
      phagolysosomes.

PMID- 11585055
TI  - AP-1 activation and altered AP-1 composition in association with increased
      phosphorylation and expression of specific Jun and Fos family proteins induced by
      vinblastine in KB-3 cells.
AB  - Vinblastine and other microtubule inhibitors are important antitumor agents that
      cause mitotic arrest, and induce apoptosis through poorly understood mechanisms,
      in a wide variety of cell lines. The activating protein 1 (AP-1) transcription
      factor is a major target of the c-Jun NH2-terminal kinase (JNK) signaling
      pathway, which is activated by microtubule inhibitors. Therefore, we examined the
      effect of vinblastine on AP-1 composition and activity in human KB-3 carcinoma
      cells. Vinblastine caused highly selective effects on AP-1 proteins in a
      concentration- and time-dependent manner. Specifically, c-Jun, expressed at a low
      level in control cells, was greatly increased and phosphorylated, Jun D was
      phosphorylated, Jun B underwent phosphorylation and subsequently became
      undetectable, and Fra 1 expression was also greatly increased. In contrast. Fra
      2, c-Fos, and Fos B were relatively unchanged by vinblastine. Changes in AP-1
      preceded caspase 3 activation and, therefore, occurred prior to the commitment
      phase of apoptosis. With the exception of c-Jun, which was not affected by
      paclitaxel, the same alterations in AP-1 proteins occurred after exposure to
      vincristine, paclitaxel, and colchicine, demonstrating that these are general
      responses to microtubule inhibition. Supershift assays demonstrated that in
      control cells, AP-1 binding activity was mediated by Jun D/Fra 2 heterodimers,
      whereas after vinblastine treatment, AP-1 complexes also containing c-Jun and Fra
      1 were present, suggesting that induction of these latter proteins by vinblastine
      is functionally significant. Consistent with these observations, vinblastine
      stimulated AP-1-dependent luciferase reporter gene transcription. These findings
      suggest that alterations in AP-1 composition and activity may be key events in
      the early response of KB-3 cells to microtubule inhibitors.

PMID- 11585056
TI  - Suppression of c-myc expression and c-Myc function in response to sustained DNA
      damage in MCF-7 breast tumor cells.
AB  - The topoisomerase II inhibitors teniposide (VM-26), doxorubicin, and amsacrine (m
      AMSA), as well as ionizing radiation, induce a transient suppression of c-myc
      mRNA, which correlates with growth inhibition of MCF-7 breast tumor cells. To
      further assess the involvement of c-mvc in the DNA damage-induced signal
      transduction pathways of the breast tumor cell, we determined the influence of
      sustained DNA damage on c-myc expression, c-Myc protein levels and c-Myc
      function. Continuous exposure of MCF-7 breast tumor cells to VM-26 induced DNA
      strand breaks that were sustained for at least 9 hr. DNA strand breakage was
      accompanied by a decline in c-myc transcripts and c-Myc protein levels by >90%
      after VM-26 exposure for 24 hr. The activity of a transcriptional target of the c
      Myc protein, ornithine decarboxylase, was reduced by approximately 75% within 9
      hr of DNA damage, in parallel to the declines in c-myc mRNA and protein levels.
      Extended exposure to VM-26 resulted in an initial loss of approximately 35% of
      the cell population followed by the death of additional cells such that by 72 hr
      only 50% of the cells were viable. Although apoptosis was evident 72 hr after
      initiating drug exposure [based on cell cycle analysis, terminal deoxynucleotidyl
      transferase-mediated dUTP nick end-labeling (TUNEL) assays, and an assessment of
      cell morphology], the primary phase of cell killing, which occurred during the
      first 24 hr was non-apoptotic. These studies indicate that non-apoptotic pathways
      can also mediate cell death in the breast tumor cell and support the role of c
      myc expression, c-Myc protein, and c-Myc function as elements of the DNA damage
      response pathway in the breast tumor cell.

PMID- 11585057
TI  - S phase dependence and involvement of NF-kappaB activating kinase to NF-kappaB
      activation by camptothecin.
AB  - Camptothecin (CPT) and derivatives are topoisomerase I poisons currently used as
      anticancer drugs. Their cytotoxicity is maximal for cells in S phase. Using
      asynchronous and S phase-synchronized HeLa cells, we showed that both the nuclear
      factor-kappaB (NF-kappaB) activation and its transcriptional activity, induced by
      CPT treatment, are enhanced in S phase cells. After CPT treatment, NF-kappaB
      activation reached a maximum within 2-3 hr and was still detectable after 24 hr.
      The nature of the complex evolved with time, forming mostly p50/p65 after 2 hr to
      almost exclusively p52 after 24 hr. In HeLa cells, the different steps of the
      induction were readily observable in S phase synchronized cells, whereas they
      were barely noticeable in a randomly growing cell population. The signal
      progressed through the activation of the IKK complex, the phosphorylation of
      IkappaBalpha, and the degradation of phosphorylated-IkappaBalpha and 
      IkappaBbeta. The stable expression of wild-type HA-tagged-IkappaBalpha or mutated
      HA-tagged-IkappaBalpha (S32,36A) allowed us to confirm the essential role of
      Ser32 and Ser36. NF-kappaB-activating kinase (NIK) could play a role upstream of
      the IKK complex, as the transient expression of a kinase inactive mutant
      NIK(K429,430A) abolished the activation of NF-kappaB by CPT. A kinase inactive
      mutant of mitogen-activated protein/ERK kinase kinase 1 (MEKK1), another kinase
      susceptible of acting upstream of the signalsome, did not. Cytotoxicity studies
      with clonal populations expressing different amounts of wild-type or mutated
      IkappaBalpha revealed that the overexpression of wild-type IkappaBa in large
      amount increases the sensitivity of HeLa cells to CPT more efficiently than a
      lower level of expression of non-phosphorylable IkappaBalpha.

PMID- 11585059
TI  - Delivery of cholesteryl-conjugated phosphorothioate oligodeoxynucleotides to
      Kupffer cells by lactosylated low-density lipoprotein.
AB  - The efficacy of antisense oligonucleotides depends on the ability to reach in
      vivo their target cells. We aim to develop strategies to enhance uptake of
      phosphorothioate oligodeoxynucleotides by Kupffer cells. To this end, we
      conjugated cholesterol to ISIS-3082, a phosphorothioate oligodeoxynucleotide
      specific for intercellular adhesion molecule-1. The cholesterol-conjugated
      oligonucleotide, denoted ISIS-9388, associated readily with lactosylated low
      density lipoprotein (LacLDL), a lipidic carrier that is taken up by galactose
      receptors on Kupffer cells. Association of up to 10 molecules of ISIS-9388 per
      LacLDL particle did not induce aggregation. LacLDL-associated [3H]ISIS-9388 was
      rapidly taken up by the liver after injection into rats (52.9+/-1.8% of the dose
      within 2 min versus 18.6+/-2.8% for ISIS-3082). N-acetylgalactosamine inhibited
      hepatic uptake, indicating involvement of galactose-specific receptors. Liver
      cells were isolated at 60 min after injection of LacLDL-associated [3H]ISIS-9388.
      Kupffer cells displayed the highest uptake: 88.1+/-24.7 ng of oligonucleotide/mg
      of cell protein, which is 6-14 times higher than after injection of free ISIS
      9388 or ISIS-3082 (15.0+/-3.8 ng and 6.3+/-1.4 ng, respectively). It can be
      calculated that Kupffer cells contribute 43.9+/-5.4% to the liver uptake (free
      ISIS-9388 and ISIS-3083 14.5+/-3.1% and 8.3+/-3.2%, respectively). In conclusion,
      conjugation of a phosphorothioate oligodeoxynucleotide with cholesterol and its
      subsequent association with LacLDL results in a substantially increased Kupffer
      cell uptake of the oligonucleotide. As Kupffer cells play a key role in
      inflammation, our approach may be utilized to improve antisense-based therapeutic
      intervention during inflammation.

PMID- 11585058
TI  - Pulmonary Cyp1A1 and CYP1A2 levels and activities in adult male and female
      offspring of rats exposed during gestation and lactation to 2,3,7, 8
      tetrachlorodibenzo-p-dioxin.
AB  - The levels and activities of pulmonary microsomal CYP1A1 and CYP1A2 in 40-day-old
      male and female, and 120-day-old male offspring of pregnant rats treated with
      five weekly 0.1 microg/kg doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      during gestation and lactation were compared with those in age-matched offspring
      of untreated dams. The CYP1A1-preferential activity, ethoxyresorufin O-deethylase
      (EROD), was comparably induced 5.3- and 6.4-fold in 40-day-old male and female
      offspring, respectively, but was not induced in 120-day-old male offspring, of
      TCDD-treated dams. Similarly, CYP1A1 protein was induced in 40-day-old female or
      male offspring of untreated dams but was undetectable in 120-day-old offspring of
      untreated or treated dams. CYP1A2 activity, as measured by the bioactivation of 2
      amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) to mutagens in the Ames assay,
      was elevated 11.1- and 5.5-fold in 40-day-old female and male offspring,
      respectively, of TCDD-treated dams, but was unaffected by TCDD exposure in 120
      day-old offspring. CYP1A2 protein was undetectable in 40-day-old male or female
      offspring of untreated dams or in 120-day-old male offspring of treated or
      untreated dams; it was detected in 40-day-old offspring of treated dams, at a
      level that was higher in females than in males. The results show that gestational
      and lactational exposure to TCDD causes long-lasting and gender-preferential
      induction of CYP1A1 as well as CYPIA2 in the lungs of rat offspring.

PMID- 11585060
TI  - A study of the expression of the xenobiotic-metabolising cytochrome P450 proteins
      and of testosterone metabolism in bovine liver.
AB  - The expression of xenobiotic-metabolising cytochrome P450 proteins in the liver
      of cattle was determined using substrate probes and immunologically by Western
      blot analysis. Compared to the rat, cattle displayed much higher coumarin 7
      hydroxylase (CYP2A) and ethoxyresorufin O-deethylase (CYP1) activity but, in
      contrast, it exhibited much lower debrisoquine 4-hydroxylase (CYP2D) and lauric
      acid hydroxylase activities (CYP4A). The ethoxyresorufin O-deethylase activity
      was markedly inhibited by furafylline and a-naphthoflavone, and coumarin 7
      hydroxylase by 8-methoxypsoralen. Immunoblot analysis employing antibodies to rat
      CYP1A1 recognised two immunorelated proteins in bovine liver whose expression
      appeared to be higher compared with rat. Kinetic studies indicated that a single
      enzyme is likely to be responsible for the O-deethylation of 7-ethoxyresorufin in
      bovine liver. When bovine microsomes were probed with antibodies to rat CYP2A2, a
      single protein was detected in cattle liver. Kinetic analysis followed by
      construction of Eadie-Hofstee plots indicated that more than one enzyme
      contributes to the 7-hydroxylation of coumarin. Immunoblot analysis employing
      antibodies to human CYP2D6 and rat CYP4A1 revealed in both cases a single, poorly
      expressed immunoreacting band in bovine microsomes. Similar immunoblot studies
      detected proteins in cattle liver immunorelated to the CYP2B, CYP2C, CYP2E, and
      CYP3A subfamilies. Bovine microsomes metabolised testosterone but, in contrast to
      the rat, failed to produce 2alpha- and 16alpha-hydroxytestosterone. On the other
      hand, bovine microsomes produced levels of another hydroxylated metabolite,
      possibly 12-hydroxytestosterone. In conclusion, results emanating from this study
      indicate the presence of proteins in the cattle liver belonging to all the
      xenobiotic-metabolising families of cytochrome P450.

PMID- 11585061
TI  - IWC meeting causes furore.

PMID- 11585062
TI  - Largest national US marine sanctuary for Florida.

PMID- 11585063
TI  - Assessment of economic losses from marine pollution: an introduction to economic
      principles and methods.
AB  - This paper introduces economic concepts and theory pertaining to public policy
      issues and concerns about pollution in marine environments. Many of these
      concepts and theories are unfamiliar to individuals and professionals outside the
      field of economics, such as biologists, ecologists, environmental lawyers, and
      even public policymakers. Yet many of these individuals observe economics in
      action, often for the first time, within a public policy arena. Exposure and a
      better understanding of the concepts and ideas in economics that are particularly
      relevant for public policies can help to achieve efficiencies in the form of
      better designed policies, and help to bridge communications gaps across other
      professions and the economics profession.

PMID- 11585064
TI  - Organic carbon flow in the Ob, Yenisey Rivers and Kara Sea of the Arctic region.
AB  - Stable carbon isotope and elemental C/N ratios of the organic fraction of a set
      of samples along a transect in the Ob and Yenisey Rivers into the Kara Sea in the
      Arctic were measured. Previously, the concentrations of 239,240Pu and 137Cs in
      these same samples had been determined. The coupled measurements were carried out
      to assess possible connectivity between organic carbon flow into the Kara Sea and
      transport of radioactive nuclides in this marine environment. Organic carbon flow
      into the Kara Sea is influenced significantly by terrigenous sources carried by
      the Ob and Yenisey Rivers. The carbon isotope-organic carbon relationship
      provides evidence that a rich source of terrigenous carbon exists in the riverine
      system. A weak, but significant relationship between stable carbon isotope ratio
      and 137Cs suggests that most of the 137Cs is derived from riverine particles, as
      compared to Pu which is also derived from in situ scavenging within the water
      column.

PMID- 11585065
TI  - Polychaetes as indicators of environmental disturbance on subarctic tidal flats,
      Iqaluit, Baffin Island, Nunavut Territory.
AB  - The polychaetes of the tidal flats near the town of Iqaluit, Baffin Island were
      analysed along gradients of environmental disturbance resulting from human
      activity. Sources of environmental disturbance include a sewage lagoon, garbage
      sites; and an area of the tidal flat that is cleared by bulldozer. Sampling of
      the tidal flats included 300 biological sediment cores taken from 75 sites along
      seven transects. Environmental disturbance has resulted in four zones of
      polychaete communities with increasing distance. The heavily disturbed zone is
      closest to the disturbances and is devoid of polychaetes. The disturbed zone
      follows and is characterized by low diversity the result of increased densities
      of a few opportunistic species such as, Capitella 'capitata' sp. The moderately
      disturbed zone is characterized by increased species diversity due to organic
      enrichment from the disturbances. The undisturbed zone, located the furthest from
      the sources of disturbance, is characterized by moderate levels of diversity
      compared to the other three zones.

PMID- 11585066
TI  - Bioindication potential of carbonic anhydrase activity in anemones and corals.
AB  - Activity levels of carbonic anhydrase (CA) were assessed in anemones Condylactis
      gigantea and Stichodactyla helianthus with laboratory exposures to copper,
      nickel, lead, and vanadium, and also in animals collected from polluted vs
      pristine field sites. CA activity was found to be decreased with increase in
      metal concentration and also in animals collected from the polluted field site.
      Preliminary assessments to adapt the CA assay for use in the widespread coral
      Montastraea cavernosa show decreased CA activity in specimens from the polluted
      field site and provide an avenue for future research aimed at more thoroughly
      describing coral CA activity for potential application in bioindication.

PMID- 11585067
TI  - Preliminary results of biomarker responses in zooplankton of brackish
      environments.
AB  - Zooplankton is an essential component of the food chains of marine and brackish
      environments. Ecotoxicological risk to zooplankton, evaluated by the biomarker
      approach, can be used as an early warning signal of risk to the health of marine
      ecosystems. The aim of this project is to evaluate the application of certain
      biomarkers in zooplankton. In the present paper, laboratory and field studies
      were performed with the copepods Acartia margalefi, Acartia latisetosa and the
      mysid Siriella clausi. Acetylcholinesterase activity (AChE) was determined in
      homogenates of whole organisms. Mean AChE activity was 10.05 micromol min g(-1)
      for A. margalefi, 3.30 micromol min g(-1) for A. latisetosa and 79.70 micromol
      min g(-1) for S. clausi. A. margalefi and S. clausi also showed a linear increase
      in enzyme activity with increasing concentrations of samples. Preliminary
      laboratory work was also carried out with specimens of A. latisetosa, which were
      exposed to an organophosphorus insecticide (parathion). Moderate inhibition of
      AChE (19%) with respect to controls was observed. AChE activities were two orders
      of magnitude higher in the zooplankton than in hemolymph samples of the decapod
      Carcinus aestuarii (Fossi et al., 1996) indicating that these species have a high
      metabolic rate, which makes them suitable for biomarker studies.

PMID- 11585068
TI  - Effects of fish farm loadings on seagrass (Posidonia oceanica) distribution,
      growth and photosynthesis.
AB  - The spatial extent and timing of the impact of fish farms on the distribution and
      performance of a Posidonia oceanica meadow were examined in an embayment of the
      south-eastern coast of Spain (Hornillo Bay, Murcia). Changes in seagrass
      distribution were determined using available seagrass mapping (from 1988, i.e.,
      before the onset of aquaculture activities and 1998) and by successive sampling
      in 1994 and 1998. Environmental variables (light attenuation coefficient, water
      column dissolved nutrients and organic content of sediments) together with plant
      performance (shoot biomass, leaf growth rate, photosynthetic activity,
      carbohydrate reserves, the number of leaves per shoot, epiphyte loads and
      herbivore pressure) were measured in plants affected by organic discharges, and
      were compared with those found in reference healthy plants over an annual growth
      cycle. Since the onset of fish farm activity, 11.29 ha of P. oceanica meadow has
      been completely lost and 9.86 ha significantly degraded, thus resulting in a
      total affected area which accounts for about 53% of the former meadow, or 7-fold
      the fish farming area. Unequal propagation of seagrass die-off or degradation
      reflects the relevance of local factors such as depth and hydrodynamism on the
      true extent of fish farm impact. Water transparency decreases and dissolved
      nutrient and organic content of sediments increases in the vicinity of cages
      compared to distant reference stations, thus supporting the notion of
      environmental gradients caused by the organic release from cages, which spreads
      outwards. Shoot size, leaf growth rate and the number of leaves per shoot in
      plants close to the fish farm decreased. Moreover, low leaf growth and low
      rhizome carbohydrate concentration (always relative to that found in an
      undisturbed area) indicated carbon budget imbalances. Since light reduction in
      the affected area was only modest (31% of light reaching the sea surface, while
      at the same depth this figure was 39% at the reference site), and light
      availability was well above the minimum requirement estimated for this species,
      neither this factor nor epiphyte overgrowth (epiphyte load was lower in the
      affected area) seem to explain such carbon imbalances or the observed meadow
      regression. Alternatively, the high herbivore pressure found in the affected zone
      suggests that overgrazing is one of the main causes of decreasing shoot sizes and
      hence of carbon imbalance, reduced growth and shoot mortality. The impact of fish
      farms on seagrasses, therefore, seems to be highly variable and depends on
      complex interactions between a large number of processes.

PMID- 11585069
TI  - The significance of imposex levels and TBT contamination in the red whelk,
      Neptunea antiqua (L.) from the offshore Irish Sea.
AB  - The extent to which open seas and oceanic waters have been contaminated by TBT is
      unclear since most sampling programmes have concentrated on inshore areas,
      particularly near harbours. Accordingly, the red whelk, Neptunea antiqua L.
      (Mollusca: Prosobranchia), a sublittoral and dioecious prosobranch species, was
      selected to investigate the potential effects of TBT-induced imposex in the
      central western Irish Sea. The presence of imposex was noted in > 90% of all
      female whelks that were examined on a monthly basis over a 12-month period.
      However, the proliferation of the vas deferens was not considered severe enough
      to affect the reproductive capabilities of the population. Low concentrations of
      butyltins were detected in the soft tissues of all whelks examined, ranging from
      0.009 to 0.112 microg g(-1) Sn dry wt There was no significant correlation
      between the documented imposex stages and total butyltin contamination,
      indicating that the species is not a reliable bioindicator species of the effects
      of this contaminant.

PMID- 11585070
TI  - Effects of chitin on microbial emulsification, mineralization potential, and
      toxicity of bunker C fuel oil.
AB  - Bunker C, one of the most frequently spilled petroleum products in the US, is
      difficult to remove from oiled surfaces and is relatively recalcitrant to
      biodegradation; therefore, emulsification and biodegradability must be optimized
      before bioremediation can be considered a viable treatment option. Sand from a
      freshly oiled beach near Dutch Harbor, Alaska, was incubated at 10 degrees C with
      nutrients (Bushnell-Haas (BH)) or nutrients with crab shell chitin (BH-C). BH-C
      amendment resulted in greater numbers of bunker C emulsifiers and greater
      mineralization potentials for hexadecane, phenanthrene, and fluorene than with BH
      only. Compared to BH alone, mineralization potentials for bunker C also were
      higher in BH-C, with an estimated 8% of fuel oil mineralized after 6 weeks.
      Microbially emulsified oil was more toxic than in uninoculated controls (p <
      0.05) as measured by Microtox assays. However, toxicity was significantly lower
      in BH-C than BH after 4 and 6 weeks incubation (p < 0.05).

PMID- 11585071
TI  - Organochlorine and trace element contamination in bottlenose dolphins (Tursiops
      truncatus) from the South China Sea.

PMID- 11585072
TI  - Baseline study of submerged marine debris at beaches in Curacao, West Indies.

PMID- 11585073
TI  - Imposex in gastropods from Argentina (South-Western Atlantic).

PMID- 11585074
TI  - Multiple herpetic whitlow lesions in a 4-year-old girl: case report and review of
      the literature.
AB  - Herpetic whitlow is a herpes simplex virus type 1 or 2 infection of the fingers
      characterised by erythema and painful, non-purulent vesicles. In children it
      typically occurs after auto-inoculation from herpes stomatitis, herpes labialis
      or genitalis. Occasionally, person-to-person transmission occurs from family
      members with herpes labialis. We report a 4-year-old girl with multiple herpetic
      whitlows secondary to herpetic stomatitis and present a review of the medical
      literature based on a systematic MEDLINE search of published paediatric patients
      (English, French and German language). Of 42 identified patients, 72% were
      younger than 2 years, most had endogenous or exogenous inoculation of herpes
      simplex virus type 1 and 65% were initially misdiagnosed as having "bacterial
      felon". Recurrences were reported in 23%. CONCLUSION: herpetic whitlow should be
      suspected based on clinical signs. Specific diagnosis can be made by polymerase
      chain reaction or culture. The high rate of misdiagnosed cases indicates that
      this entity is not sufficiently known. Lesions are self-limited; surgical
      interventions can be harmful and should be avoided. Recurrences occur as
      frequently as in adults.

PMID- 11585075
TI  - Serological rebound in congenital toxoplasmosis: long-term follow-up of 133
      children.
AB  - Although serological rebound is common in infants with congenital toxoplasmosis,
      clinical recommendations for management, in particular the need for additional
      treatment, vary. The goals of our retrospective cohort study in 133 consecutive
      children with congenital toxoplasmosis were to estimate the incidence and
      duration of the rebounds, identify predictive factors, assess the long-term risk
      of eye lesions and the need for treatment. We first estimated the incidence and
      duration of rebounds and identified predictive factors using an univariate
      analysis and a Cox model modified to include time-dependent variables. Two cohort
      studies were then conducted to compare the incidence density of secondary eye
      lesions in children who had a rebound versus no rebound, and among children who
      had a rebound after initial therapy, in those who received an additional course
      of treatment and in those who did not. Of the 133 children, 93 (70%) had at least
      one rebound during a mean follow-up of 95 months. Of those with one rebound
      diagnosed after initial treatment, 33 received an additional 3-month course of
      pyrimethamine/sulphadoxine and 48 were not treated. Intracranial calcification at
      birth was associated with an increased relative risk (RR) of rebound (RR = 2.601;
      P = 0.03), and treatment with pyrimethamine/sulphadoxine between 2 and 12 months
      of age with a decreased risk (RR = 0.3; P = 0.0845), whereas age of pregnancy at
      maternal infection, type of treatment during pregnancy and sex were not found to
      be predictive factors. There was no difference in incidence densities of
      secondary eye lesions in children without rebound (7/3,367 child-months) compared
      to those with at least one rebound (22/9,609 child-months) (RR = 1.10; 95% CI:
      0.47-2.58), and, among the 81 children who had one rebound diagnosed after
      initial treatment, in those who received an additional course of treatment and in
      those who did not (RR = 0.72; 95% CI: 0.30-1.72). CONCLUSION: serological rebound
      is common in children with congenital toxoplasmosis but, due to the risk and
      constraints, an additional course of treatment and more ophthalmological
      surveillance than currently practiced do not seem warranted.

PMID- 11585076
TI  - Community and nosocomially acquired respiratory syncytial virus infection in a
      German paediatric hospital from 1988 to 1999.
AB  - Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract
      infections in infants. Since epidemiological data from Germany are scarce, a
      large retrospective hospital based analysis was performed. In the first part of
      the study, laboratory records were checked for RSV positive specimens from
      January 1988 to December 1997. A total of 1664 specimens were positive
      corresponding to 1171 episodes in 1064 patients; 88% were up to 4 years old and
      47% up to 3 months old. The percentage of premature newborns from all patients 0
      4 years old was 24%. The rate of nosocomial infection was 38%. The core RSV
      season began in December, lasted until April, and peaked in January and February.
      In the second part of the study, from April 1, 1997 to March 31, 1999, which
      encompassed two RSV winter seasons, patients with the ICD-9 coded discharge
      diagnoses of lower respiratory tract infections, bronchopulmonary dysplasia (BPD)
      and prematurity were analysed. Of the premature newborns, 25% were tested RSV
      positive at least once up to the age of 1 year, as were 52% of those with BPD.
      The rehospitalisation rate due to RSV infection was 22% in patients with BPD, and
      8.9% in all premature newborns. Of patients with community acquired RSV
      infection, 12% required intensive care and 6% had to be ventilated mechanically.
      The mortality rates in both parts of the study were 0.8% and 0.7%, respectively.
      CONCLUSION: Respiratory syncytial virus infection in young children is also of
      major importance in Germany. Although the mortality rate is low, the high
      incidence and the severity of the disease in the particular risk group of
      premature infants with chronic lung disease contribute to a very high disease
      burden.

PMID- 11585077
TI  - "Adult" form of muscular carnitine palmitoyltransferase II deficiency:
      manifestation in a 2-year-old child.
AB  - We describe a 6-year-old girl admitted with acute muscular weakness and pain
      which made her unable to walk. Her parents reported a 4-year history of similar
      episodes which occurred once or twice a year and always resolved spontaneously.
      Laboratory investigations showed elevated serum creatine kinase which peaked at
      day 2 of the attack with 18,600 U/l. Carnitine palmitoyltransferase-II deficiency
      was suspected based on the determination of serum acylcarnitines by tandem mass
      spectrometry which showed a characteristic elevation of long-chain C16 and C18:1
      acylcarnitines. The diagnosis was confirmed by impaired in-vitro palmitate
      oxidation in blood and the detection of a homozygous substitution S113L in the
      carnitine palmitoyltransferase-II gene. CONCLUSION: Carnitine
      palmitoyltransferase-II deficiency should be included in the differential
      diagnosis of isolated muscular weakness even when manifesting in early childhood.

PMID- 11585078
TI  - Growth and development of children to 4 years of age after repeated antenatal
      steroid administration.
AB  - It is common practice to repeat antenatal steroid administration after 7 to 10
      days in women who continue to be at risk for preterm delivery. However, safety
      and efficacy of repeated courses have not been established. Mothers of singleton
      infants who had more than five courses of betamethasone (80-120 mg cumulative
      dose) were eligible for this cohort study. Index patients (IP) were compared to
      concurrent controls who had < or = 1 course but were matched for sex and
      gestational age. Of 35 IP born between 1986 and 1995 in a single perinatal
      centre, 28 were available for follow-up and could be matched. There was no
      difference between groups with respect to maternal age and gestational age at
      delivery. Median gestational age at initial treatment was 26.3 weeks (25th
      percentile 25.1 weeks, 75th percentile 27.2 weeks) in IP. There was no
      significant difference between groups in head circumference, length and body
      weight at birth and at age 4 years. The ability to sit and to walk without
      assistance and to use two-word phrases was attained at similar ages. The use of
      glasses or hearing aids, allergies, asthma or recurrent upper respiratory
      infections were not reported more frequently in IP. CONCLUSION: This study failed
      to ascertain adverse long-term effects of repeated antenatal steroid
      administration in infants and children to the age of 4 years. In contrast to a
      similar Australian study, we were unable to demonstrate a lower birth size in
      exposed infants even though our sample size for women with more than five courses
      and their cumulative doses were larger.

PMID- 11585079
TI  - Nasopharyngeal oxygen therapy produces positive end-expiratory pressure in
      infants.
AB  - The World Health Organisation recommends nasopharyngeal catheters as a safe and
      efficient method of oxygen administration in infants. However, little is known
      about the mechanisms of the improvement in oxygenation. The aim of the present
      study was to determine whether nasopharyngeal oxygen therapy produces positive
      end-expiratory pressure (PEEP). Nine spontaneously breathing infants (median age
      13 months, range 10 days to 20 months) after heart surgery were investigated. All
      patients had normal pulmonary blood flow at the time of the study (Qp:Qs=1:1).
      Oxygen (oxygen fraction 1.0) was delivered by an 8 F catheter inserted into the
      nasopharynx (tip just visible below the soft palate). The pulmonary mechanics
      were analysed using a single compartment model of the respiratory system.
      Oesophageal pressure (Pes) at end-expiration, dynamic lung compliance (C(L)) and
      resistance (R(L)), minute ventilation, PaCO2 and PaO2 were measured at baseline
      without a nasopharyngeal catheter or oxygen, and at oxygen flows of 0.5 l/min,
      1.0 l/min and 2.0 l/min. All the flows generated significant increases in PEEP.
      Mean difference in PEEP (SD, paired t-test versus baseline): 1.6 cm H2O (1.4,
      P=0.008) with 0.5 l/min of oxygen; 2.8 cm H2O (2.7, P=0.014) with 1.0 l/min of
      oxygen; and 4.0 cm H2O (2.9, P = 0.004) with 2.0 l/min of oxygen. There was a
      significant correlation between all the nasopharyngeal flows (in ml/kg per min)
      and the generated PEEP (P<0.001) and between the C(L) values and the generated
      PEEP (P < 0.05). There was no significant difference in PaCO2 and R(L). Minute
      ventilation was significantly less with nasopharyngeal oxygen than at baseline.
      As expected, PaO2 increased significantly with increasing oxygen flows.
      CONCLUSION: Administration of oxygen through an 8 F nasopharyngeal catheter at
      flow rates recommended by the World Health Organisation (0.5 l/min in newborns,
      1.0 l/min in infants) produces moderate amounts of positive end-expiratory
      pressure. The levels achieved may contribute to an improvement in oxygenation by
      altering the visco-elastic properties of the lung.

PMID- 11585080
TI  - Short stature homeobox-containing gene deletion screening by fluorescence in situ
      hybridisation in patients with short stature.
AB  - The short stature homeobox-containing gene (SHOX) on the short arm of the X and Y
      chromosomes is an important determining factor of stature phenotype. Absence of
      the SHOX gene is a main cause for short stature in patients with Turner syndrome.
      Mutations of the SHOX gene can also be responsible for Leri-Weill syndrome
      (dyschondrosteosis). The aim of this study was to determine the frequency of SHOX
      deletions in short stature children and to delineate indications for SHOX
      deletion screening. Out of 50 probands, 35 had idiopathic short stature, 12 cases
      showed additional anomalies of the forearms (in particular Madelung deformity)
      and three patients were affected by a congenital heart defect. Chromosomal
      investigations with fluoresence in situ hybridisation did not reveal a SHOX
      deletion in any patient with idiopathic short stature. In five of the 12 patients
      (41.7%) with anomalies of the forearms, a SHOX deletion on one sex chromosome
      could be detected. No deletion was observed in the three cases with additional
      heart defects. CONCLUSION: The frequency of short stature homeobox-containing
      gene deletions in patients with idiopathic short stature appears to be very low
      and does not require a fluorescence in situ hybridisation analysis. Short stature
      in association with anomalies of the forearms such as Madelung deformity makes a
      deletion more probable and therefore screening for such deletions is recommended
      in these cases.

PMID- 11585081
TI  - Children with epilepsy after withdrawal of anticonvulsive therapy: psychiatric
      behaviour and neuropsychological abilities.
AB  - Do children who remain in remission with epilepsy after withdrawal of
      anticonvulsive therapy still exhibit a different behaviour and performance
      related abilities compared to healthy children? It was the aim of this study to
      investigate whether these children showed deviating psychiatric behaviour and/or
      neuropsychological function deficits as compared with a healthy control group and
      with children following occasional seizures which had never been treated. The
      study comprised 39 children with epilepsy after withdrawal of anticonvulsive
      therapy, 37 children with occasional seizures, and 39 matched healthy control
      children who were tested with regard to psychiatric and neuropsychological
      criteria. The patients were aged 6-15 years; 28 had a primarily generalised
      epilepsy, and 11 had a focal epilepsy. The patients remained free from seizures
      for more than 1 year. Psychiatric testing comprised the Child Behavior Checklist
      by Achenbach and Edelbrock and the Mannheim Parent Interview. Neuropsychological
      testing included non-verbal intelligence, visual perception, short-term memory
      and learning ability, arithmetics, movement coordination and motor skills, fine
      motor skills and verbal functions. After withdrawal from anticonvulsive therapy,
      the children with epilepsy did not exhibit any psychiatric disturbances, whereas
      those with occasional seizures frequently showed behaviour problems. After
      withdrawal from anticonvulsive therapy, no neuropsychological deficits were found
      in the children with epilepsy as compared to those with occasional seizures or to
      healthy children. Risk factors for poorer test results were first seizures
      occurring before the age of 3 years, delayed development, and neonatal problems.
      CONCLUSION: Children with epilepsy who remained without relapse after withdrawal
      from the anticonvulsive therapy did not show any psychiatric abnormalities and
      their performance was comparable to that of healthy control children, provided no
      risk factors were present.

PMID- 11585082
TI  - Randomised controlled trial of the effect of cisapride on the pyloric muscle in
      preterm infants.
AB  - In this study we determined the effects of cisapride on the pyloric muscle in
      preterm infants. To perform a randomised, double blind, placebo controlled study,
      two groups each of 16 preterm newborns were given either cisapride (0.2 mg/kg
      every 8 h) or a placebo for at least 7 days. Infants were studied first on the
      day when treatment with cisapride or placebo was to be initiated (time 0), and
      then after 3 (time 1) and 7 days (time 2). In each group, the following
      parameters were studied by ultrasonography: cross-sectional diameter of the
      entire pylorus, muscle thickness, and length of the pyloric canal. Also, the mean
      daily total gastric aspirate volume was studied for the entire week of the study.
      At time 0, we observed no significant differences between the two groups with
      respect to diameter, muscle thickness and length of the pyloric muscle. At time 1
      and time 2, both diameter and muscle thickness were significantly greater in the
      cisapride group than in the placebo group. Furthermore, the length of the pyloric
      canal was significantly greater in the cisapride group than in placebo group at
      time 2, though not so at time 1. For the entire week of the study, we found a
      significantly larger mean daily total gastric aspirate volume in the group of
      infants treated with cisapride compared to the placebo treated group. CONCLUSION:
      Cisapride significantly affects all of the main measurements of the pyloric
      muscle and causes a significantly larger amount of daily total gastric aspirate
      volume. Its use to promote feeding intolerance in preterm newborns cannot be
      recommended.

PMID- 11585083
TI  - Effect of salbutamol on lung function parameters of healthy children.
AB  - In the present study, the effect of 200 microg salbutamol compared to placebo was
      evaluated on lung function parameters of 37 healthy children aged 7-14 years.
      Salbutamol or placebo were administered, using a single blind study design, and
      spirometry was performed before and after 10 min of inhalation. At the time of
      the study, all children were symptom-free and had not suffered from any
      respiratory infection during the previous 4 weeks. The administration of
      salbutamol resulted in a significant increase of mean forced expiratory volume in
      1 s (111%-115%, P<0.05), maximal expiratory flow at 50% of forced vital capacity
      (101%-110%, P<0.05) and maximal expiratory flow at 25 % of forced vital capacity
      (96%-115%, P<0.05). The administration of placebo resulted in no significant
      change in lung function parameters. CONCLUSION: The administration of 200 microg
      salbutamol results in the occurrence of a small but significant bronchodilation
      in healthy, non-asthmatic children.

PMID- 11585084
TI  - Hyperkalaemic cardiac arrest in a manifesting carrier of Duchenne muscular
      dystrophy following general anaesthesia.

PMID- 11585085
TI  - Epidemiology of respiratory syncytial virus infection among paediatric inpatients
      in northern Taiwan.

PMID- 11585086
TI  - The impact of traditional management on seasonal internal parasite burdens and
      productivity of indigenous Tswana goats in southern Botswana.
AB  - Data collected monthly over a period of two years were live weight, packed cell
      volume (PCV), nematode faecal egg counts (FECs) and coccidial oocyst counts from
      faecal analyses for 100 mixed age (3-7 years) indigenous Tswana does. The aims of
      this experiment were to determine seasonal FECs and coccidial oocysts in these
      goats and quantify the relationships of these burdens to liveweight and PCV. FECs
      significantly (P < 0.05) varied with season, with the warmer seasons viz spring,
      summer and autumn having higher log (x + 1) parasite burdens than the cooler
      winter, while seasonal trends for coccidial oocysts were not obvious. PCV was
      also significantly (P < 0.05) lower in the warmer seasons than winter. FECs and
      coccidial oocysts in all seasons were less than the mean log (x + 1) of 3.3
      inferred to reduce production in small stock. Correlation coefficients were
      strongly negative: -0.95 for FECs and liveweight and -0.84 for FECS and PCV,
      indicating that these worms had a negative impact on productivity. A further
      study should be conducted to quantify the effects of controlling these parasites
      during the warm seasons on productivity.

PMID- 11585087
TI  - Prevalence of virulent Rhodococcus equi in isolates from soil collected from two
      horse farms in South Africa and restriction fragment length polymorphisms of
      virulence plasmids in the isolates from infected foals, a dog and a monkey.
AB  - The prevalence of virulent Rhodococcus equi in soil isolates from two horse farms
      in South Africa and nine clinical isolates from six foals, a foal foetus, a dog,
      and a monkey was investigated. The isolates were tested for the presence of
      virulence plasmid DNA and 15- to 17-kDa antigens by immunoblotting. Rhodococcus
      equi was isolated from almost all of the soil samples obtained from the two farms
      with 5.0 x 10(1) to 3.3 x 10(4) colony forming units per gram of soil. Virulent
      R. equi was isolated from three soil samples from one of the farms and appeared
      in 3.8% (three of 80 isolates), but not in any of the 182 isolates from the other
      farm. Of the three virulent R. equi isolates, one contained an 85-kb type I
      plasmid and two an 87-kb type I plasmid. Of nine clinical isolates from the
      foals, foal foetus, dog and monkey, five from the foals were virulent R. equi
      which expressed the virulence-associated antigens and contained a virulence
      plasmid 85-kb type I, and were all isolated from cases of pneumonia typical of
      that induced by R. equi in young foals living in widely separated areas in South
      Africa. The isolates from the other four foals, the dog and the monkey were
      avirulent R. equi.

PMID- 11585088
TI  - Helminths in dogs belonging to people in a resource-limited urban community in
      Gauteng, South Africa.
AB  - One hundred and sixty-four faecal samples, 148 adhesive tape swabs and 132 blood
      samples were collected from dogs in Boksburg, Gauteng, to assess the prevalence
      of helminth parasites in the area. Sixty-nine of these dogs were also necropsied
      and helminths recovered from the gastro-intestinal tracts. Ancylostoma caninum
      was the most common helminth and was present in 88% of the dogs, followed by
      Dipylidium caninum in 39% of dogs, Toxocara canis in 36%, Ancylostoma braziliense
      in 20%, Spirocerca lupi in 14%, Toxascaris leonina in 9%, Trichuris vulpis in 6%,
      Joyeuxiella pascualei in 6% and Taenia spp. in 4%. Microfilariae of Dipetalonema
      reconditum were found in 2% of the blood samples. The results of this study
      extend the geographic distribution of T. vulpis. With the exception of Spirocerca
      and Dipetalonema, all these helminths are potentially zoonotic, and may pose a
      threat to community health.

PMID- 11585089
TI  - The epidemiology of tuberculosis in free-ranging African buffalo (Syncerus
      caffer) in the Kruger National Park, South Africa.
AB  - The presence of bovine tuberculosis (Mycobacterium bovis) in the Kruger National
      Park (KNP) was determined for the first time in 1990. It was diagnosed in an
      African buffalo (Syncerus caffer) bull, which was found recumbent and in an
      emaciated and moribund state near the south-western boundary fence. This prompted
      an investigation into the bovine tuberculosis (BTB) status of the KNP, with
      emphasis on its epidemiological determinants and risk factors. This report
      documents the findings of surveys that were conducted from 1990 to 1996. It was
      found that BTB had entered the KNP ecosystem relatively recently (+/- 1960), and
      has found favourable circumstances for survival and propagation in a fully
      susceptible and immunologically naive buffalo population. Indications are that it
      entered the KNP from across the southern river boundary, where the presence of
      infected domestic cattle herds had been documented. From there the infection
      spread through the southern buffalo population and is currently spreading in a
      northward direction. It was estimated that this northward spread took place at a
      rate of about 6 km per year; the prospect being that, if this rate of spread is
      maintained, the entire KNP may be affected in less than 30 years from now.
      Spillover from buffalo had already occurred in species such as chacma baboon
      (Papio ursinus), lion (Panthera leo), cheetah (Acinonyx jubatus), kudu
      (Tragelaphus strepsiceros) and leopard (Panthera pardus). Although there is no
      indication yet that these species act as maintenance hosts, the possibility is
      raised that these, or an as yet overlooked species, might assume such a role in
      future. In the KNP, BTB manifests itself as a chronic and predominantly
      subclinical disease in buffalo. It may take years for clinical signs to develop,
      and then only at a terminal stage, when emaciation is a constant feature. It is
      suspected that the time from infection to death is variable and dependent on the
      animal's immune response, which can be weakened by such factors as stress, old
      age or droughts. It was found that, in the interim, buffalo have a normal
      reproductive life. On necropsy, buffalo show almost exclusively lung and upper
      respiratory tract involvement, pointing to an aerogenous mode of transmission.
      Histologically, little sign of encapsulation of lesions was detected, which
      suggests that they are exceptionally susceptible to BTB and that most lesions are
      open and infectious and progressive, leading ultimately to death of the
      individual. Evidence also indicates that BTB is progressive within the herd
      context (92% being the highest prevalence rate thus far determined in a buffalo
      herd) as well as progressive within the KNP buffalo population (the implication
      being that virtually all buffalo herds in the KNP will eventually be infected).
      Preliminary data suggest a positive correlation between disease prevalence and
      mortality, with potential mortality reaching up to 10% in buffalo herds having
      BTB prevalence rates of 50 % and higher. Only the future will tell what the
      effect of the disease on the population dynamics of buffalo will be.

PMID- 11585090
TI  - Rapid detection and differentiation of Newcastle disease virus isolates by a
      triple one-step RT-PCR.
AB  - A triple one-step RT-PCR was developed to screen and differentiate virulent from
      avirulent Newcastle disease virus (NDV) isolates. Three sets of oligonucleotides
      were designed, each specific for amplifying NDV fusion protein gene-specific RNA
      from virulent, avirulent or all isolates respectively. The sensitivity of one
      step RT-PCR was determined using viral RNA extracted from serially diluted NDV
      infected allantoic fluid and found to be 10(-5) HA units. Application of one-step
      RT-PCR to various NDV samples, including wild-type virulent isolates and
      avirulent vaccine strains, demonstrated the potential for rapid identification (3
      4 h) of NDV isolates as well as the differentiation of virulent from avirulent
      strains.

PMID- 11585091
TI  - Parasites of domestic and wild animals in South Africa. XL. Ticks on dogs
      belonging to people in rural communities and carnivore ticks on the vegetation.
AB  - Ixodid ticks were collected at weekly intervals from February 1999 to April 2000
      from domestic dogs belonging to people in rural communities in north-eastern
      KwaZulu-Natal. Seven ticks were identified to species level and adult
      Haemaphysalis leachi followed by immature Amblyomma hebraeum and adult
      Rhipicephalus simus were the most prevalent. Infestation with adult H. leachi was
      most intense during February and March 1999 and from January to April 2000, and
      least intense during October 1999. Infestation with adult R. simus was most
      intense during February and March 1999 and least during July and September of the
      same year. For 12 consecutive years, from August 1988 to July 2000, free-living
      ticks were collected at monthly intervals from the vegetation of two landscape
      zones in the Kruger National Park. Most adult H. leachi were collected in the one
      zone from March to June, and no ticks were collected in October, whereas, with
      the exception of March, most were collected in the other zone during the period
      January to June, and only one tick was collected in October. Most adult R. simus
      were collected during February and March at both localities and only a single
      tick was collected in September. Adult Rhipicephalus turanicus was present only
      in the one zone and was collected only from January to June.

PMID- 11585092
TI  - Intestinal helminths of four species of skinks (Mabuya) (Sauria: Scincidae) from
      southern Africa.
AB  - Intestinal helminths are reported from four species of scincid lizards from
      southern Africa: Mabuya occidentalis, Mabuya spilogaster, Mabuya striata and
      Mabuya variegata. The helminth fauna consisted of one species of Cestoda,
      Oochoristica truncata and five species of Nematoda, Abbreviata paradoxa,
      Maxvachonia dimorpha, Parapharyngodon rotundatus, Spauligodon petersi and
      Thubunaea fitzsimonsi. All findings represent new host records. Ascarid larvae
      were also found. It appears that Mabuya is infected by generalist helminths that
      occur in other species of African lizards.

PMID- 11585093
TI  - Vaccination to control an outbreak of Mycoplasma crocodyli infection.
AB  - Details of a severe outbreak of M. crocodyli infection in farmed crocodiles are
      reported. The outbreak was suspected to have been precipitated by translocation
      related stress on the animals brought from a farm with a known history of M.
      crocodyli infection. Resorting to the use of an autogenous vaccine proved more
      effective in alleviating the disease manifestations than antibiotic therapy.
      Prospects of vaccination in the face of an outbreak are discussed.

PMID- 11585094
TI  - Alternative cell lines for the propagation of lumpy skin disease virus.
AB  - In our Institute lumpy skin disease virus is grown on primary lamb testis cells
      for isolation, identification and vaccine production. However, the availability
      of lambs in Kenya has been seriously reduced over the past few years. This has
      led to an increase in the cost of using primary lamb testis cells. This study was
      undertaken to investigate other primary cell lines, which are easily available
      and provide an equivalent or better yield of lumpy skin disease virus. Foetal
      bovine muscle (FBM) cells were found to be an adequate alternative for lamb
      testis cells.

PMID- 11585095
TI  - Continuous in vitro propagation of Cowdria ruminantium (Welgevonden stock) in a
      canine macrophage-monocyte cell line.
AB  - The Welgevonden stock of Cowdria ruminantium, aetiologic agent of heartwater, was
      continuously propagated in DH82 cells, a continuous canine macrophage-monocyte
      cell line. Cultures of DH82 cells were readily infected provided that the culture
      medium was supplemented with cycloheximide. Cultures were split at regular 3-day
      intervals and infection rates ranged between 60% and 95%. Cultures were
      continuously propagated through more than 125 passages over a period of more than
      one year.

PMID- 11585096
TI  - Seroprevalence of Toxoplasma gondii and Chlamydia psittaci in domestic pigeons
      (Columbia livia domestica) at Sebele, Gaborone, Botswana.
AB  - High antibody titres to Toxoplasma gondii and Chlamydophila psittaci were
      demonstrated in serum collected from domestic pigeons at average titres of 1:128
      and 1:64 respectively. The public health implications of these findings are
      discussed.

PMID- 11585097
TI  - Immunohistochemical and histopathological studies of fixed rabies virus in goats.
AB  - The purpose of this study was to systematically demonstrate and compare the
      pathological and immunohistochemical changes in goats which were infected by a
      fixed rabies virus that was used in vaccine production. In the histopathological
      examinations, varying degrees of inflammatory, degenerative and necrotic changes
      were detected in the central nervous system. In the preparations stained by the
      immunoperoxidase (IP) method, intra- and/or extracellular viral antigens were
      observed on the cerebellum, cornu ammonis, thalamus, pons, nucleus caudatus,
      spinal cord, medulla oblongata, Gasserian ganglion, eye and retropharyngeal lymph
      nodes. In the preparations stained by the immunofluorescence (IF) method, intra-
      and/or extracellular viral antigens were seen in the same locations with the
      exception of the retropharyngeal lymph nodes. It was also observed that the
      antigens were qualitatively and quantitatively well stained with both methods.
      However, the visibility of antigens in the retropharyngeal lymph nodes and eye,
      and the facilities of applying made the IP method much more advantageous than the
      IF method.

PMID- 11585098
TI  - Changes in some factors of the innate immunity and serum zinc and iron
      concentrations in pigs following intravenous administration of Escherichia coli
      lipopolysaccharide.
AB  - The changes in some factors of the innate immunity (phagocytosis, complement,
      lysozyme); haematological parameters-leukocytes, erythrocytes, differential white
      blood cell counts, haemoglobin, haematocrit and the serum concentrations of the
      microelements zinc and iron in six 2- to 3-months-old female piglets after the
      intravenous administration of lipopolysaccharide from Escherichia coli 0111:B4
      were determined. It was found out that 1 h after the administration of
      lipopolysaccharide at the dosage rate of 10 microg/kg body weight resulted in a
      decrease in the phagocytic parameters, i.e. the phagocytic number and the index
      of phagocytic activity, which was followed by an increase in their values between
      post treatment hours 2 and 4. The leukocyte counts had decreased by hour 2 after
      the injection, but thereafter increased, and at post treatment hour 72, a
      leukocytosis was observed. The differential white blood cell counts were
      characterized by a shift to the left between hours 2 and 4 and a statistically
      significant increase in lymphocyte counts at hour 48 of the experiment. The serum
      zinc concentrations were increased an hour after the lipopolysaccharide
      application; after which their average values were lower. The haemolytic
      activities (CH50) of the classical and the alternative pathways of complement
      activation decreased. The haemolytic activity (CH50) for the classical pathway
      began to increase at hour 48 following the treatment. Significant changes were
      not observed in lysozyme activity, serum iron concentrations or the related
      haematological parameters (erythrocytes and haemoglobin).

PMID- 11585099
TI  - Treatment of viral hepatitis--2001.
AB  - Chronic viral hepatitis may now be controlled and, in many cases, permanently
      eradicated. Rapid advances in the antiviral therapy of chronic hepatitis C
      infection have resulted in a greater than 50% sustained response rate, with
      genotypes 2 and 3 now considered 'curable diseases.' Current hepatitis B therapy
      leads to significant improvement in liver histology and overall survival. These
      advances, coupled with the fact that 8% of the world population is chronically
      infected with viral hepatitis, has sparked considerable interest in this
      condition on the part of the pharmaceutical industry. In 2001, the most effective
      therapy for chronic hepatitis C is the combination of pegylated interferon alpha
      and oral ribavirin. The treatment of hepatitis B consists of either interferon
      alpha or oral lamivudine, while newer nucleoside/nucleotide analogues, alone or
      in combination with existing therapy, are being explored.

PMID- 11585100
TI  - Oestrogenic and antiandrogenic chemicals in the environment: effects on male
      reproductive health.
AB  - Exposures of human populations to pesticides and industrial pollutants, and to
      synthetic chemicals present in foods, beverages, and plastics, have raised
      concern that these substances can interfere with endogenous sex hormone function.
      Interference with sex hormone action can, in turn, result in a variety of
      developmental and reproductive anomalies. Compounds in this class are thus
      referred to as endocrine disruptors (EDs). EDs that affect reproductive processes
      in vertebrates act primarily by altering oestrogenic and antiandrogenic
      activities. The recent cloning of a second oestrogen receptor (ER) subtype
      (ERbeta) and its widespread tissue distribution pattern indicates that the first
      ER to be cloned, ERalpha, may not be the only, or even the primary, mediator of
      oestrogen action. It is anticipated that this discovery will lead to development
      of antagonist compounds specific to either ER subtype, and help to determine the
      function of each receptor subtype in reproductive and other tissues. Growing
      evidence suggests that EDs interfere with reproductive function at low exposure
      levels and cause distinct effects at different concentrations within the same
      organ. Developing organisms have increased susceptibility to the actions of EDs
      because differentiating tissues are more vulnerable to changes in hormonal
      milieu. Thus, children are at greater risk of toxicant-related illnesses than
      adults. However, most data are collected from laboratory studies, and it remains
      to be determined that the levels of chemicals in the environment can impair human
      reproductive health. There is also significant genetic variability between human
      and animal species in their reactions to chemicals. The effects of low-dose,
      chronic, and multiple chemical exposures warrant further investigation in order
      to characterize the risk of environmental agents to humans. The aims of this
      review, which will focus on male reproduction, are to: 1) identify synthetic
      chemicals in the environment that fall into the ED class; 2) describe their
      mechanisms of toxicity in reproductive tissues; and, 3) outline the direction of
      future research efforts with respect to EDs.

PMID- 11585101
TI  - Impact of FDG-labelled positron emission tomography imaging on the management of
      non-small-cell lung cancer.
AB  - Lung cancer is currently the leading cause of cancer-related death in both men
      and women in most Western countries. Although 5-year survival rates have doubled
      from 1960s, they are low compared with survival rates for other cancer types.
      Tumour stage is the strongest prognostic factor and the most important parameter
      that guides treatment decision making. Metabolic imaging with fluorodeoxyglucose
      labelled positron emission tomography (FDG-PET) has proved superior to
      conventional imaging for staging of non-small-cell lung cancer. This new imaging
      modality permits more accurate planning of treatment with surgery and
      radiotherapy and provides information of greater prognostic significance than
      what can be obtained with conventional approaches. FDG-PET has been approved in
      the USA and the UK as a basic and invaluable tool in the management of lung
      cancer. This paper reviews current trends in clinical practice on the
      applications of FDG-PET in the management of non-small-cell lung cancer.

PMID- 11585102
TI  - Familial hypercholesterolaemia in Finland: common, rare and mild mutations of the
      LDL receptor and their clinical consequences. Finnish FH-group.
AB  - Familial hypercholesterolaemia (FH) is an autosomal co-dominantly inherited
      condition resulting from mutations of the low-density lipoprotein (LDL) receptor
      which occur in heterozygous form in approximately one in 500 individuals.
      Clinically, FH is characterized by 2-3-fold elevation of serum LDL cholesterol
      levels, accelerated development of atherosclerotic vascular disease, and, if
      untreated, shortened lifespan. The Finnish population, which represents a genetic
      isolate, offers exceptional possibilities for genetic-epidemiological studies on
      FH, as a handful of founder gene mutations account for the majority of FH cases
      in Finland. This review summarizes data from our FH studies carried out since
      1985. We wish to emphasize the continuum of genotype-phenotype relationships, the
      importance of molecular diagnosis, the detection of novel risk factors of
      vascular disease, and innovations inhibiting cholesterol absorption for the
      modern treatment of FH.

PMID- 11585103
TI  - Brain natriuretic peptide-guided therapy for heart failure.
AB  - The drug treatment of heart failure, once simple, has become complex. Apart from
      a loop diuretic and digoxin, most patients should now be receiving an angiotensin
      converting enzyme inhibitor (or angiotensin II receptor blocker), a beta-blocker
      and spironolactone. Newer drugs, such as endothelin-receptor antagonists and
      combined blockers of converting-enzyme and neutral endopeptidase, might soon
      become available. When to introduce these drugs and what dose is optimal for any
      individual, are questions that currently vex clinicians. We proposed that plasma
      levels of the cardiac hormone brain natriuretic peptide (BNP, or better, its 1-76
      amino-acid N-terminal fragment, N-BNP), would provide an objective index for
      guiding drug treatment in patients with established, stable cardiac failure. In a
      pilot study, 69 patients were randomized to drug treatment based on clinical
      criteria, or based on plasma levels of N-BNP. After a median follow-up of 9.6
      months, those in the N-BNP group had fewer clinical end-points than those in the
      group managed by clinical criteria alone (19 vs 54; P= 0.02). These preliminary
      data encourage the concept that the increasingly complex pharmacotherapy for
      heart failure, both chronic (as in this trial) and acute, might best be guided by
      an objective measure such as plasma levels of BNP or N-BNP.

PMID- 11585104
TI  - Imprinted genes and mental dysfunction.
AB  - There is a rapidly accumulating body of evidence from family, adoption and twin
      studies suggestive of a genetic component to many common mental disorders. In
      some cases, the transmission of abnormalities has been shown to be dependent upon
      the sex of the parent from whom they are inherited. Such 'parent-of-origin
      effects' may be explained by a number of genetic mechanisms, one of which is
      'genomic imprinting'. In imprinted genes one allele is silenced according to its
      parental origin. This in turn means that imprinted traits are passed down the
      maternal or paternal line, in contrast to the more frequent Mendelian mode of
      inheritance that is indifferent to the parental origin of the allele. In the
      present review, we survey the evidence for the influence of imprinted genes on a
      number of mental disorders, ranging from explicit imprinted conditions, where in
      some cases abnormalities have been mapped to particular gene candidates, to
      examples where the evidence for parent-of-origin effects is less strong. We also
      consider, briefly, the wider implications of imprinted effects on mental
      dysfunction, in particular with respect to evolutionary pressures on mammalian
      brain development and function.

PMID- 11585105
TI  - Association of trypsin-2 with activation of gelatinase B and collagenase-2 in
      human bronchoalveolar lavage fluid in vivo.
AB  - BACKGROUND: Tissue injury mediated by matrix metalloproteinases (MMPs) is a
      hallmark of inflammatory lung diseases. Latent secreted proMMPs must be activated
      to be catalytically competent. AIM: Our aim was to analyse an involvement of the
      trypsin-2, trypsin-2-alpha1-proteinase inhibitor (PI) complex and tumour
      associated trypsin inhibitor (TATI) in the in vivo activation of proMMP-8, -9 and
      -2. METHODS: Concentrations of trypsin-2, trypsin-2-alpha1-PI complex and TATI in
      bronchoalveolar lavage fluid (BALF) were analysed by immunofluorometry. Molecular
      forms and expression of trypsin-2 and trypsin-2-alpha1-PI complex were identified
      by Western immunoblot and immunocytochemistry. Gelatinolytic and collagenolytic
      activities were measured by substrate-based activity assays. RESULTS: BALFs from
      16 of 43 patients and BALFs from five of 15 healthy controls contained trypsin-2
      alpha1-PI complex. TATI was found in all healthy control BALFs (median 0.12
      microg/L, range 0.02-0.66 microg/L) whereas 8 of 43 BALFs from patients (median
      0, range 0-0.64 microg/L, P = 0.0001) contained TATI. Patient BALFs showed
      significantly increased activation of MMP-9 and MMP-8 compared with healthy
      controls. The concentrations of trypsin-2-alpha1-PI complex correlated with the
      in vivo activation of MMP-9 and -8 (r = 0.68, P = 0.002 and r = 0.61, P = 0.008)
      but not with the activation of MMP-2 in BALFs. CONCLUSION: Results show a key
      role of trypsin-2 in the in vivo activation of proMMP-8 and -9 in inflammatory
      lung diseases.

PMID- 11585106
TI  - Coeliac disease in patients with cerebellar ataxia of unknown origin.
AB  - BACKGROUND: Neurological symptoms of unknown origin are common in coeliac disease
      (CD). Evidence suggests that CD may also contribute to the development of
      idiopathic late-onset ataxia. AIM: To evaluate the frequency of CD in patients
      with cerebellar ataxia of unknown origin. METHODS: The medical files of adult
      patients with the diagnosis of cerebellar ataxia of unknown origin (n=44) were
      evaluated. Serum gliadin, endomysial, and serum tissue transglutaminase
      antibodies were used as screening tests for CD. Subjects with positive results
      were referred to small-bowel biopsy. RESULTS: The frequency of CD was as high as
      9.1% in all patients. A thorough interview and review of the patient files
      indicated alcohol abuse as a cause for cerebellar disease in almost half (45.5%)
      of our patients. When the cases with alcohol abuse were omitted, the calculated
      frequency of CD was 16.7% in patients with ataxia of unknown origin. CONCLUSION:
      CD is a common association with cerebellar disease and the disease should be
      considered in all patients with ataxia of unknown origin.

PMID- 11585107
TI  - Muscle strength and motor function in children and adolescents with spinal
      muscular atrophy II and III.
AB  - The aim of this study was to quantify isometric muscle strength and motor
      function in children and adolescents with spinal muscular atrophy (SMA) and to
      analyse the impact of reduced muscle strength on motor function. Six children and
      adolescents with SMA II and eight with SMA IlI were assessed regarding isometric
      muscle strength and motor function. Isometric muscle strength was tested with a
      myometer and the values obtained were compared with normative data. Motor
      function was videotaped and 20 movements were scored according to a three-point
      scale. All of the assessed children and adolescents with SMA II and SMA III
      showed reduced muscle strength, but there were great differences within the
      group. The typical pattern of muscle weakness in SMA, with proximal weakness
      greater than distal and the lower limbs more affected than the upper, was also
      seen in these children. The muscle weakness affected motor function in all
      assessed children. Walking, transfer from lying or sitting to the standing
      position and stair-climbing were possible in some of the children, despite marked
      reduction of muscle strength. The study increases our knowledge concerning the
      degree of muscle weakness in children with SMA and the impact of muscle weakness
      on motor function. The results increase our possibilities of understanding the
      prerequisites for everyday life in these children and planning therapeutic
      interventions. Repeated assessments with the methods used in this study may be
      used to monitor the course of the disease and to evaluate the efficacy of
      treatment.

PMID- 11585109
TI  - Rasmussen's syndrome associated with chronic brain stem encephalitis.
AB  - We report a 3-year-old boy with a clinical picture of Rasmussen's encephalitis
      who had clinical, radiological and pathological evidence of brain stem
      involvement resulting in death. In addition, there were unexpected
      neuropathological findings of severe bilateral mesial temporal sclerosis. We
      discuss the novel finding of brain stem involvement in this condition and the
      association with mesial temporal sclerosis.

PMID- 11585108
TI  - Brain MRI findings in influenza A-associated acute necrotizing encephalopathy of
      childhood.
AB  - Acute necrotizing encephalopathy following influenza A is frequently reported
      from Japan and Taiwan but is very rarely seen in Western countries. We describe a
      10-year-old boy with acute necrotizing encephalopathy, who developed symmetrical
      thalamic and brain stem lesions seen on magnetic resonance imaging (MRI).
      Serological confirmation of influenza A was made 2 weeks after the onset of
      symptoms. The child made a full recovery. This case is interesting because of its
      rarity in European countries, the striking brain MRI findings and the good
      neurological outcome.

PMID- 11585110
TI  - Central/nervous system/neuromuscularchannelopathies.

PMID- 11585111
TI  - Neuronal ceroid lipofuscinoses.

PMID- 11585112
TI  - The limb-girdle muscular dystrophies.

PMID- 11585113
TI  - In vitro kinetic evaluation of titanium alloy biodegradation.
AB  - The present controlled in vitro experiment evaluated the dissolution kinetics of
      titanium (Ti), aluminum (Al) and vanadium (V). Titanium alloy (Ti90Al6V4) dental
      implants were inserted in 1.8 ml sterile tubes, containing equal volumes of NaCl
      0.9% (w/v) and human serum. Metallic elements released by the atomic process of
      corrosion were measured at pH 7.2 and 37 C by atomic absorption spectrophotometer
      at 1, 3, 6, 9, 15, 21, 27, 33, 42, 51, 60, 69, 78, 87 and 96 days. Ti dissolution
      averaged 16+/-5 ng/cm2/day and 1565 ng/cm2 over the experimental period. Al
      dissolution was stable at 9+/-5 ng/cm2/day and averaged 945 ng/cm2 over the 96
      day period. V dissolution was stable at 0.15+/-0.18 ng/cm2/day after the sixth
      day of incubation and averaged 42 ng/cm2 over the 96-day period. Major
      disparities in atomic dissolution were detected among implants. No local or
      systemic reaction to titanium has been documented. In contrast, 4% toxic V and 6%
      Al may suffice to elicit local and systemic reactions or inhibit cellular
      proliferation and differentiation.

PMID- 11585114
TI  - Chewing sticks: timeless natural toothbrushes for oral cleansing.
AB  - It is generally accepted that oral hygiene maintenance through regular removal of
      dental plaque and food deposits is an essential factor in the prevention of
      dental caries and periodontal disease. Methods for oral hygiene vary from country
      to country and from culture to culture. Despite the widespread use of
      toothbrushes and toothpastes, natural methods of tooth cleaning using chewing
      sticks selected and prepared from the twigs, stems or roots from a variety of
      plant species have been practised for thousands of years in Asia, Africa, the
      Middle East and the Americas. Selected clinical studies have shown that chewing
      sticks, when properly used, can be as efficient as toothbrushes in removing
      dental plaque due to the combined effect of mechanical cleaning and enhanced
      salivation. It has also been suggested that antimicrobial substances that
      naturally protect plants against various invading microorganisms or other
      parasites may leach out into the oral cavity, and that these compounds may
      benefit the users by protection against cariogenic and periodontopathic bacteria.
      Some clinical epidemiological studies are in support of this, and many laboratory
      investigations have suggested the presence of heterogeneous antimicrobial
      components extractable using different chemical procedures. A few recent studies
      have identified some of the active antimicrobial compounds. Today, chewing sticks
      are still used in many developing countries because of religion and or tradition,
      and because of their availability, low cost and simplicity. The World Health
      Organization also encourages their use. The Year 2000 Consensus Report on Oral
      Hygiene states that chewing sticks may have a role to play in the promotion of
      oral hygiene, and that evaluation of their effectiveness warrants further
      research.

PMID- 11585115
TI  - Localized antimicrobial peptide expression in human gingiva.
AB  - The stratified epithelia of the oral cavity are continually exposed to bacterial
      challenge that is initially resisted by innate epithelial factors and by the
      recruitment of neutrophils. Antimicrobial peptides from phagocytes and epithelia
      contribute to this antimicrobial barrier. Using antibodies and in situ
      hybridization, we explored antimicrobial peptide expression in the varied
      epithelia of the periodontium and in cultured gingival epithelial cells. In
      gingival tissue, mRNA for the beta-defensins, human beta-defensin 1 (hBD-1) and
      human beta-defensin 2 (hBD-2) was predominately localized in suprabasal
      stratified epithelium and the peptides were detected in upper epithelial layers
      consistent with the formation of the stratified epithelial barrier. In cultured
      epithelial cells, both hBD-1 and -2 peptides were detected only in
      differentiating, involucrin-positive epithelial cells, although hBD-2 required
      stimulation by proinflammatory mediators or bacterial products for expression.
      Beta-defensins were not detected in junctional epithelium (JE) that serves as the
      attachment to the tooth surface. In contrast, alpha-defensins and cathelicidin
      family member LL-37 were detected in polymorphonuclear neutrophils (PMNs) that
      migrate through the JE, a localization that persists during inflammation, when
      the JE and surrounding tissue are highly infiltrated with PMNs. Thus, the
      undifferentiated JE contains exogenously expressed alpha-defensins and LL-37, and
      the stratified epithelium contains endogenously expressed beta-defensins. These
      findings show that defensins and other antimicrobial peptides are localized in
      specific sites in the gingiva, are synthesized in different cell types, and are
      likely to serve different roles in various regions of the periodontium.

PMID- 11585116
TI  - Hypothalamic-pituitary-adrenal axis activation by experimental periodontal
      disease in rats.
AB  - Organisms respond to inflammatory conditions by mounting a co-ordinated complex
      series of adaptive responses involving the immune, nervous and endocrine systems
      that are aimed at restoring the homeostatic balance. We have recently shown in a
      rat model that inappropriate hypothalamic-pituitary-adrenal (HPA) axis regulation
      and a subsequent inability to mount a suitable glucocorticoid response to
      gingival inflammation may influence susceptibility to periodontal disease. This
      study was designed to investigate whether ligature- and bacterial
      lipopolysaccharide (LPS)-induced inflammation in the gingival connective tissues
      may activate this physiological axis, and to further explore the significance of
      HPA regulation in periodontal disease. Experimental periodontal disease was
      induced in major histocompatibility complex (MHC)-identical but HPA low (LEW) and
      high (F344) responding rat strains. We tested (1) whether ongoing periodontal
      disease activates the HPA axis as measured by corticosterone levels, and (2)
      whether genetic differences in HPA regulation modulate periodontal disease
      progression. In the F344 strain. the periodontal tissue destruction was more
      severe. This observation was associated with a significant increase of
      corticosterone levels in F344 rats only. Addition of LPS at the gingival
      inflammatory site led to a further increase of corticosterone levels and disease
      severity in F344 rats. These findings illustrate a positive feedback loop between
      the HPA axis and periodontal disease: the disease activates the HPA axis, and a
      genetically determined high HPA responsivity further increases disease
      susceptibility.

PMID- 11585117
TI  - The effects of a high-carbohydrate diet on the stress-strain behavior of the
      periodontal ligament of the distal root of the mandibular first molar in
      hamsters.
AB  - We analyzed stress-strain curves in transverse sections at three different root
      levels of the cervical, middle, and apical regions of the distal root of the
      mandibular first molar in hamsters fed a high-carbohydrate (experimental group)
      or standard (control group) diet for 8 weeks. Each section was loaded in vitro at
      a rate of 5 mm/min in an extrusive direction. The rupture sites and the
      structures of birefringent collagen fibers in the periodontal ligament were also
      analyzed. The maximum shear stress, tangent modulus, and failure strain energy
      density of the periodontal ligament were significantly greater in the cervical
      region than in the middle and apical regions in both the control and experimental
      groups. The maximum shear stress, tangent modulus, and failure strain energy
      density of the periodontal ligament in the experimental group were significantly
      lower than those in the control group at the cervical and middle regions. The
      maximum shear strain was significantly greater in the experimental group than in
      the control group at the middle and apical regions. Histological sections showed
      that the periodontal ligament ruptured irregularly in both groups. The
      collagenous fibers of the ligament in the experimental group appeared to be
      thinner and less birefringent at the cervical and middle regions of the root.
      These results suggest that a high-carbohydrate diet differentially affects the
      collagen fibers in the periodontal ligament as a function of the root level, and
      that these effects are evident in changes in the mechanical properties of the
      ligament.

PMID- 11585118
TI  - Levels of tissue inhibitor of metalloproteinases-1 and matrix metalloproteinases
      1 and -8 in gingival crevicular fluid following treatment with enamel matrix
      derivative (EMDOGAIN).
AB  - The mechanism of enamel matrix derivative (EM D) action on the periodontal wound
      healing process is not well understood. However, earlier in vitro studies from
      our laboratory demonstrated that EMD stimulated the proliferation of both
      periodontal ligament and gingival fibroblast cells. Therefore, the purpose of
      this study was to further evaluate the effect of EMD on the early wound healing
      process by assessing the protein levels of matrix metalloproteinases (MMPs) and
      tissue inhibitors of metalloproteinases (TIMPs) in gingival crevicular fluid
      (GCF). Sixteen patients, each of whom had one or two pairs of infrabony defects
      located contralaterally in the same arch, were included in this clinical trial.
      Thirty-six infrabony defects were randomly assigned treatment with flap surgery
      plus EMD or flap surgery plus placebo. At baseline and at 2, 4 and 12 week follow
      up evaluation visits, GCF was sampled with paper strips. After determination of
      GCF volume, TIMP-1, MMP-1 and MMP-8 GCF levels were measured by an enzyme-linked
      immunosorbent assay. Intragroup analysis: At week 2 following surgery, when
      compared to baseline all parameters in each study group, except MMP-1,
      significantly increased (p<0.05). There were no significant differences between 4
      or 12 weeks and baseline in either study group. Intergroup analysis: At 4 weeks
      after surgery, GCF volume and TIMP-1 levels showed a significant decrease
      (p<0.05) in the EMD group, when compared to the placebo group. MMP-1 levels at
      weeks 2, 4 and 12, and MMP-8 levels at weeks 4 and 12 were significantly lower (p
      < 0.05) in the EMD group compared to the placebo group. EMD compared to placebo
      treated sites demonstrated a more rapid return to baseline levels of TIMP-1, MMP
      1 and MMP-8. These findings suggest that treatment with flap surgery and EMD,
      compared to flap surgery with placebo, accelerated healing at an earlier stage of
      wound healing following surgery.

PMID- 11585119
TI  - The fibrillar structure of the cemento-dentinal junction in different kinds of
      human teeth.
AB  - The cemento-dentinal junction was examined in human maxillary incisors, canines
      and premolars by scanning electron microscopy combined with NaOH maceration. The
      NaOH maceration was used to remove interfibrillar substances and to observe
      details of the fibrillar architecture. The teeth were half-sectioned
      longitudinally, demineralized and macerated for 3-4 days or for 10-14 days. In
      the 3-4 day-macerated specimens, longitudinal sections of the cemento-dentinal
      junction were examined. In the 10-14 day-macerated specimens, the cementum was
      detached and the inner cementum surface facing the cemento-dentinal junction was
      examined. Observations suggested that cemental fibrils intermingle with dentinal
      fibrils only in places at the cemento-dentinal junction in both acellular and
      cellular cementum. These structural features were consistent in all kinds of
      teeth investigated here. Using human molars, we have previously proposed that the
      adhesion of proteoglycans is a main factor for the cemento-dentinal attachment
      and that the fibril intermingling between dentin and cementum is an accessory or
      secondary factor. The present study suggests that this applies to other kinds of
      human teeth.

PMID- 11585121
TI  - Osteopontin in gingival crevicular fluid.
AB  - Osteopontin (OPN) is a major glycosylated phosphoprotein in bone matrix and is
      produced by several cells including osteoblasts, osteoclasts and macrophages. OPN
      levels increase in active sites of bone metabolism. Recently, several bone
      related proteins were identified in gingival crevicular fluid (GCF) to seek
      markers of alveolar bone resorption in periodontal disease. In this study, we
      investigated the existence of OPN in GCF and the correlation between OPN level in
      GCF and probing depth (PD) of sampling sites in 98 periodontitis patients and 35
      healthy subjects. An immunoblotting analysis using 10% polyacrylamide gel showed
      that two forms of OPN with molecular masses of 54 and 66 kDa and several degraded
      fragments were detected in most GCF samples from diseased sites (PD > 4 mm). In
      GCF samples from healthy sites (PD < or = 3 mm), only one form (54 kDa) was
      observed, but any degraded fragments were not detected. When OPN amounts in GCF
      samples were determined by ELISA, a weak. but significant correlation was
      observed between OPN amount in GCF and PD (r=0.32, p=0.0013). These results
      demonstrate that OPN exists in GCF and that OPN level in GCF increases with the
      progression of periodontal disease.

PMID- 11585120
TI  - Attachment, proliferation and differentiation of periodontal ligament cells on
      various guided tissue regeneration membranes.
AB  - The purpose of this study was to evaluate the biological effects of guided tissue
      regeneration (GTR) membrane materials, per se, on the periodontal tissue
      regeneration. Rat periodontal ligament (PDL)-derived cells were used to study the
      attachment, proliferation and differentiation, in vitro, on various GTR
      membranes. Five commercially available membranes bovine type I collagen (BioMend;
      BM), bovine type I atelocollagen (Tissue Guide; TG), polylactic acid (Epi-Guide;
      EG), co-polymer of polylactic acid and polyglycolic acid (Resolute; RL) and
      expanded polytetrafluoroethylene: e-PTFE (Gore Tex; GT)-were examined. A 3 x 3 mm
      section of the membrane was fixed to the bottom of a 35 x 10 mm style culture
      dish and plated with 2 ml of cell suspension at an initial density of 5 x 10(4)
      cells/ml in culture medium with 10% fetal bovine serum. For cell growth analysis,
      the specimens were fixed with 10% buffered formalin and stained with hematoxylin
      at 1.5 hours and 1, 3 and 5 days after cell seeding. The number of cells included
      in a unit area of 0.25 mm2 were counted under light microscopy. As a comparative
      scaffold of cell proliferation, a plastic cover for cell culture slip (Celldesk;
      CD) was used. For analysis of cell differentiation, activity of alkaline
      phosphatase (ALP) and calcification were histochemically revealed after 2-week
      cultivation. The initial number of PDL cells attached to the membrane at 1.5
      hours after cell seeding was different among membranes. RL, TG and EG had the
      same level of attached cell numbers as that on CD, while the cell numbers on GT
      and BM were significantly lower than that on CD (p < 0.01). The rate of cell
      proliferation with time also differed among the membranes examined. RL and BM
      demonstrated a significantly higher number of cells at 5 days than at 1.5 hours
      (p < 0.01). TG had increased numbers of cells at 3 and 5 days after cell seeding.
      However, there was no statistical difference between the cell numbers at 1.5
      hours and 5 days after cell seeding (p > 0.1). EG had a similar number of cell
      attachments to that at 1.5 hours throughout the experimental period. There was
      almost no cell proliferation on GT. Cell clusters of ALP positive cells and foci
      of calcification were seen on all membranes except for GT, where a scant number
      of cells were seen. Results from this study implied that GTR membrane materials,
      per se, may influence cell proliferation and differentiation in the process of
      periodontal tissue regeneration.

PMID- 11585122
TI  - Upregulation of matrix metalloproteinase-1 production by prostaglandin F2alpha in
      human gingival fibroblasts.
AB  - In the present study, we investigated the effect of prostglandin F2alpha
      (PGF2alpha) and combination of PGF2alpha and interleukin(IL)-1beta on matrix
      metalloproteinase (MMP)-1 production in human gingival fibroblasts (HGF).
      PGF2alpha enhanced MMP-1 production in a dose-dependent manner in HGF.
      Combination of PGF2alpha and IL-1beta induced a synergistic increase of MMP-1
      production in HGF. Furthermore, fluprostenol, a specific FP receptor agonist,
      increased MMP-1 production and induced a synergistic enhancement of IL-1beta
      induced MMP-1 production in HGF, similar to PGF2alpha. FP receptor mRNA
      expression was detected in HGF, by reverse transcription-polymerase chain
      reaction. Northern blot analysis revealed that PGF2alpha enhanced MMP-1 mRNA
      expression in HGF and that PGF2alpha increased MMP-1 mRNA levels induced by IL
      1beta. In conclusion, we suggest that PGF2alpha increases MMP-1 production in HGF
      and synergistically enhances MMP-1 production in IL-1beta-stimulated HGF.
      PGF2alpha may be involved in degradation of connective tissue in periodontal
      lesions.

PMID- 11585123
TI  - A new and versatile method for determination of thiolamines of biological
      importance.
AB  - A method for the separation and quantitation of several important biological
      thiolamines is described. The procedure employs a C18 reversed-phase HPLC system
      to separate the dinitrophenyl derivatives of reduced and oxidized glutathione and
      cysteine and relies on an internal standard, Nepsilon-methyllysine, to minimize
      experimental error. The method was validated in three matrices (water, HepG2 cell
      lysates, and mouse liver homogenates) using several criteria. The detector
      response was linear for the dinitrophenyl derivatives of glutathione, glutathione
      disulfide, cysteine, and cystine in the concentrations ranging from 10 to 50
      nmol/ml. Inter- and intra-day variation, percent recovery in the biological
      matrices, and limits of detection and quantitation were determined. For the most
      accurate determination, it is essential that standard curves be produced daily
      and in the same matrix as that being analyzed.

PMID- 11585124
TI  - Determination of 5-hydroxy-N-methyl-2-pyrrolidone and 2-hydroxy-N
      methylsuccinimide in human plasma and urine using liquid chromatography
      electrospray tandem mass spectrometry.
AB  - A method for simultaneous determination of 5-hydroxy-N-methyl-2-pyrrolidone (5
      HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) was developed. These compounds
      are metabolites from N-methyl-2-pyrrolidone (NMP), a powerful and widely used
      organic solvent. 5-HNMP and 2-HMSI were purified from plasma and urine by solid
      phase extraction using Isolute ENV+ columns, and analysed by liquid
      chromatography coupled to a mass spectrometer fitted with an atmospheric pressure
      turbo ion spray ionisation interface in the positive ion mode. The method was
      validated for plasma and urine concentrations from 0.12 to 25 microg/ml. The
      recoveries for 5-HNMP and 2-HMSI in plasma were 99 and 98%, respectively, and in
      urine 111 and 106%, respectively. For 5-HNMP and 2-HMSI, the within-day precision
      in plasma was 1-4 and 3-6%, respectively, and in urine 2-12 and 3-10%,
      respectively. The corresponding data for the between-day precision was 5 and 3
      6%, respectively, and 4-6 and 7-8%, respectively. The detection limit for 5-HNMP
      was 4 ng/ml in plasma and 120 ng/ml in urine. For 2-HMSI, it was 5 ng/ml in
      plasma and 85 ng/ml in urine. The method is applicable for analysis of plasma and
      urine samples from workers exposed to NMP.

PMID- 11585126
TI  - Validated method for the determination of hydroquinone in human urine by high
      performance liquid chromatography-coulometric-array detection.
AB  - The paper describes the computer aided method development and validation for the
      determination of hydroquinone in human urine from a clinical study on renal
      excretion of hydroquinone metabolites and the release of free hydroquinone in the
      urinary tract in order to evaluate the proposed urine disinfecting concept. The
      presented method uses high-performance liquid chromatography on reversed-phase
      material with a polar endcapping (Aqua-C18, 250x4.6 mm). Selective and sensitive
      determination (LOQ= 12.5 ng on-column) of the target compound was achieved by
      electrochemical array detection (CoulArray). Gradient and parameter optimization
      were supported by DryLab software in order to minimize efforts of the expensive
      and time-consuming method development. Specificity and selectivity were carried
      out by separation experiments involving the prodrug arbutin and the metabolites
      hydroquinone, hydroquinone glucuronide, and hydroquinone sulfate, respectively.
      Hydroquinone glucuronide reference standard was obtained from in vitro
      glucuronidation in a rat liver microsomes assay. The method was validated
      according to the criteria for validation of pharmaceutical bioanalytical methods
      as drafted by the US Department of Health and Human Services, 1998.

PMID- 11585125
TI  - Extraction and isolation of avermectins and milbemycins from liver samples using
      unmodified supercritical CO2 with in-line trapping on basic alumina.
AB  - A multi-residue supercritical fluid extraction (SFE) method has been developed
      for the extraction and isolation of eprinomectin, moxidectin, abamectin,
      doramectin and ivermectin residues from animal liver. Liver samples are mixed
      with hydromatrix and packed into a vessel containing 2 g of basic alumina. The
      samples are extracted at 100 degrees C using unmodified supercritical carbon
      dioxide (SF-CO2) at a pressure of 300 bar and flow-rate of 5.0 l/min. The
      analytes are adsorbed in-line on the basic alumina trap, which is later eluted
      with 4 ml of methanol-ethyl acetate (70:30, v/v). After evaporating to dryness,
      sample extracts are derivatised using methylimidazole, trifluoroacetic anhydride
      and acetic acid at 65 degrees C for 30 min. Derivatised sample extracts are
      analysed by high-performance liquid chromatography (HPLC) with fluorescence
      detection. The method was validated using bovine liver fortified at levels of 4
      and 20 microg/kg with the drugs. The mean recovery ranged between 76 and 97%. The
      intra- and inter-assay variations showed RSD values <10 and <16%, respectively.
      The procedure was also applied to ovine and porcine liver, giving similar
      results. The limit of quantitation of the method is 2 microg/kg.

PMID- 11585127
TI  - Retention pharmacokinetic and pharmacodynamic parameter relationships of
      antihistamine drugs using biopartitioning micellar chromatography.
AB  - Antihistamines are drugs which act by competitive inhibition of the H1 or H2
      histamine receptors. Little has been known about their clinical pharmacokinetics
      and biological responses until the last few years. In this paper, we propose
      quantitative retention-activity relationship, QRAR, models based on the retention
      data of antihistamines in a biopartitioning micellar chromatography (BMC) system
      using a Brij35 mobile phase for describing pharmacokinetic parameters such as
      half-life and volume of distribution, or the pharmacodynamic parameters,
      therapeutic plasma levels, lethal doses and drug-receptor dissociation constant.
      The predictive ability of these models is statistically validated. These results
      are compared to traditional quantitative structure-activity relationship, QSAR,
      models using lipophilicity data. The adequacy of QRAR models can be explained
      taking into account the fact that the retention of compounds in BMC depends on
      their hydrophobic, electronic and steric characteristics which are of great
      importance in pharmacokinetic and pharmacodynamic behavior.

PMID- 11585128
TI  - Simple and rapid liquid chromatographic-turbo ion spray mass spectrometric
      determination of topiramate in human plasma.
AB  - We present a simple and fast method for the determination of the novel
      antiepileptic drug topiramate in human plasma by high-performance liquid
      chromatography coupled with turbo ion spray mass spectrometry. Plasma sample pre
      treatment was based on simple deproteinization by acetonitrile. Liquid
      chromatographic analysis was carried out on a reversed-phase column (C18, 125x4
      mm I.D., 5 microm) using acetonitrile-ammonium acetate buffer, pH 6.3 as the
      mobile phase, at a flow-rate of 0.8 ml/min. Retention time for topiramate was 2.1
      min. The detector was a single quadrupole mass spectrometer coupled to a turbo
      ion spray ion source and a heated nebulizer probe, operating in the positive ion
      mode. Ion source temperature was off; voltage was +5800 V; nebulizer and curtain
      gas flow-rates were 6 and 10 ml/min, respectively. Calibration curves for
      topiramate were linear over the range 1 to 20 microg/ml. Absolute recovery ranged
      between 92 and 95%. Intra- and inter-assay precision was <4%. The present
      procedure, omitting extraction and drying steps, is faster and simpler than the
      previously reported analytical methods for topiramate and was demonstrated to
      possess adequate sensitivity for routine therapeutic drug monitoring in plasma
      from patients with epilepsy.

PMID- 11585129
TI  - Determination of cycloserine in human plasma by high-performance liquid
      chromatography with fluorescence detection, using derivatization with p
      benzoquinone.
AB  - A new method for determining cycloserine in plasma samples is described. This
      method is based on the derivatization of cycloserine with p-benzoquinone, a
      reaction that takes place at the same time as the process of plasma
      deproteinization due to the presence of ethanol as solvent in the solution of the
      derivatization reagent. Four derivatives are obtained from this reaction. The
      main derivative is well correlated with the cycloserine concentration. The ratio
      between the volumes of the plasma sample and the reagent solution is 1:2 for a p
      benzoquinone concentration of 1000 microg/mL. Elution from a C18 column was
      isocratic, using a mobile phase containing (v/v) 85% aqueous 0.1% formic acid
      solution, and 15% (v/v) of a mixture of methanol and acetonitrile (1:1), with a
      flow-rate of 1 mL/min, at 25 degrees C. Determinations by fluorescence detection
      were achieved with excitation at 381 nm and emission at 450 nm, with a detection
      limit of 10 ng/mL for an injection volume of 5 microL. This method was validated
      and applied to the determination of cycloserine in blood plasma samples of
      several healthy volunteers.

PMID- 11585131
TI  - Validation of a method for the detection and confirmation of nitroimidazoles and
      corresponding hydroxy metabolites in turkey and swine muscle by means of gas
      chromatography-negative ion chemical ionization mass spectrometry.
AB  - The results of a validation study of a GC-NCI-MS method for the quantitative
      determination of 5-nitroimidazoles [1,2-Dimethyl-5-nitroimidazole (dimetridazole,
      DMZ), 1-methyl-2-[(carbamoyloxy)methyl]-5-nitroimidazole (ronidazole, RNZ), 1-(2
      hydroxyethyl)-2-methyl-5-nitroimidazole (metronidazole, MNZ) and 2-isopropyl-1
      methyl-5-nitroimidazole (ipronidazole, IPZ)] including the hydroxy metabolites of
      these agents [2-hydroxymethyl-1-methyl-5-nitroimidazole (HMMNI), 1-(2
      hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole (MNZOH), and 1-methyl-2-(2'
      hydroxyisopropyl)-5-nitroimidazole (IPZOH)] in turkey and swine muscle are
      presented. The validation was carried out according to the requirements of the
      draft for the revision of Commission Decision 93/256/EC, which is expected to be
      adopted by the European Commission in due course. The determination of the
      method's performance parameters revealed decision limits (CCalpha) between 0.65
      and 2.8 microg/kg for DMZ, RNZ/HMMNI, MNZ and MNZOH. Confirmatory analyses
      according to the requirements of the forthcoming EC decision are possible for all
      analytes except for IPZ and IPZOH where already the decision limits (CCalpha)
      were higher (5.2 microg/kg) than for the above-mentioned nitroimidazoles. The
      within-laboratory reproducibility and the mean recovery were in an acceptable
      range for all analytes.

PMID- 11585130
TI  - Delta(2)-oxazolines-1,3 and N-acylaziridines as potential proinsecticides of
      carboxylic acids. V. Direct thin-layer chromatography monitoring of the
      metabolism in locust tissues.
AB  - Modern thin-layer chromatography (TLC) was used for the evaluation of delta2
      oxazolines-1,3 I and N-acylaziridine VII structures, as potential proinsecticides
      of carboxylic acids III. Thus the unmasking2 of the active principles III from
      delta2-oxazolines-1,3 Ia-c and N-acylaziridine VIIc was monitored by spotting
      aliquots directly onto RP-18 TLC plates, without any sample pretreatment during
      in vitro assays performed in concentrated locust tissues. To achieve a good
      separation of carboxylate IIIa from endogenous components of the tissues, a short
      preliminary development with methanol or ion-pairing was necessary. From UV-TLC
      chromatograms (densitograms) it appeared that in a phosphate buffer at pH 7.4,
      the oxazoline Ia with a C2 substituent devoid of alpha-ramification or alpha,beta
      insaturation hydrolysed slowly into the corresponding beta-hydroxylamide VIa and
      intermediate aminoester Va. Significantly, locust mesenteron (or fat body)
      efficiently triggered the unmasking of IIIa, a transformation which corresponds
      to the expected proinsecticide behavior of Ia. Conducting TLC monitoring in the
      same locust tissues also revealed that the oxazolines Ib and Ic with an alpha
      ramification and an alpha,beta-insaturation, respectively, cannot be considered
      as proinsecticides of the corresponding carboxylic acids IIIb and IIIc. In
      contrast, the N-acylaziridine VIIc appeared as a convenient proinsecticide
      structure for masking the carboxylic acid IIIc.

PMID- 11585132
TI  - Chiral analysis of methylphenidate and dextromoramide by capillary
      electrophoresis.
AB  - Capillary electrophoretic methods have been developed to separate the enantiomers
      of methylphenidate (MPH) and dextromoramide. For MPH separation was achieved with
      heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DMCD) as chiral selector in a 100
      mM phosphoric acid buffer adjusted to pH 3.0 with triethanolamine. Commercial
      samples of D,L-erytho-MPH HCl and D,L-threo-MPH HCl were analysed using the
      method. There was no evidence of the presence of D,L-threo-MPH HCl in D,L-erytho
      MPH HCl and vice versa. The ratio of the enantiomers was determined for each
      diastereoisomer. Hydroxypropyl-beta-cyclodextrin was the chiral selector of
      choice for the chiral separation of the enantiomers of moramide. The separation
      which gave a resolution of about 3.5 was achieved in 4 min using only a 6 cm of
      length of capillary. In a sample of dextro-R-moramide tartrate only a small
      quantity (4.9% w/w) of levo-S-moramide was detected with this method.

PMID- 11585133
TI  - Polydispersity of liposome preparations as a likely source of peak width in
      capillary zone electrophoresis.
AB  - Negatively charged liposomes consisting of
      phosphatidylcholine/phosphatidylglycerol/cholesterol in various ratios when
      subjected to capillary zone electrophoresis (CZE) in Tris-HCl (pH 8) buffer of
      different concentrations have been shown previously to exhibit a size-dependent
      migration rate at low ionic strength. The present study, focusing on the peak
      width under those conditions, shows that the polydispersity of liposomes
      correlated with, and appears to be a dominant source of, the peak width of the
      liposomes in CZE in a buffer of low ionic strength (2 to 5 mM Tris-HCl buffer, pH
      8) at moderate electric field strengths (200 V cm(-1) or less). This finding,
      beyond allowing for the analysis of liposome polydispersity by CZE, suggests that
      the size-dependent fractionation of liposome preparations by a preparative
      electrophoretic technique such as free-flow electrophoresis is potentially
      feasible.

PMID- 11585134
TI  - Determination of natural corticosteroids in urine samples from sportsmen.
AB  - A method for the determination of natural corticosteroids (cortisone, cortisol,
      5beta-dihydrocortisone, 5beta-dihydrocortisol, tetrahydrocortisone and
      tetrahydrocortisol) found in the urine of sportsmen, was developed using a
      capillary gas chromatography-mass spectrometry ion trap system. 17alpha
      Methyltestosterone was used as an internal standard. The different
      corticosteroids were determined from the peak area ratios of the [M]; [M-90] and
      [M-90-90] fragment ions of their methoxime-trimethylsiyl derivatives. Sensitivity
      (15 ppb), specificity, accuracy (96%) and reproducibility (RSD=4-10%) of the
      method were demonstrated to be satisfactory for measuring the urinary
      concentrations of the selected natural corticosteroids.

PMID- 11585135
TI  - Quantification of naltrexone and 6,beta-naltrexol in plasma and milk using gas
      chromatography-mass spectrometry. Application to studies in the lactating sheep.
AB  - A selective gas chromatography-mass spectrometry method using solid-phase
      extraction has been developed for the detection and quantification of naltrexone
      and its metabolite, 6,beta-naltrexol in plasma and milk from humans and sheep at
      pharmacologically relevant concentrations. Di- or tri-acetyl derivatives were
      formed and quantified by selected-ion monitoring. Recoveries of naltrexone (30
      microg/l) and 6,beta-naltrexol (250 microg/l) from both human plasma and milk
      were greater than 70%. Intra-assay and inter-day precision ranged from 3 to 21%
      for naltrexone and 2-18% for 6,beta-naltrexol for all matrices investigated, with
      an overall mean accuracy of 104% for naltrexone, and 99% for 6,beta-naltrexol.
      Human samples containing these analytes were stable for at least 3 weeks at -20
      degrees C or 6 weeks at -80 degrees C. Analysis of the plasma and milk from the
      lactating sheep showed mean milk-to-plasma ratios of 55 for naltrexone and 3 for
      6,beta-naltrexol.

PMID- 11585136
TI  - Solid-phase microextraction and gas chromatography-mass spectrometry analysis of
      p,p' -DDE in biological samples.
AB  - A simple and rapid extraction method for the analysis of p,p'-DDE from rat whole
      blood and tissues was developed using headspace solid-phase microextraction
      (SPME). A vial containing a sample of p,p'-DDE, sodium hydroxide, and
      benzophenone as internal standard was heated at 120 degrees C. A
      polydimethylsiloxane-coated SPME fiber was exposed for 15 min in the headspace of
      the vial. The fiber needle was then injected and desorbed by exposing the fiber
      in the injection port of a capillary gas chromatography-mass spectrometry system.
      The calibration curve demonstrated good linearity throughout the concentration
      range from 0.02 to 50 microg/g for rat whole blood and liver samples. The limit
      of detection for p,p'-DDE was 0.020 microg/g using 0.5 g rat whole blood and
      liver samples. Coefficients of variation ranged from 7.0 to 7.9%. This method was
      used to analyze a rat whole blood sample after administration of p,p'-DDE.

PMID- 11585137
TI  - Determination of D- and L-aspartate in cell culturing medium, within cells of
      MPT1 cell line and in rat blood by a column-switching high-performance liquid
      chromatogrpahic method.
AB  - HPLC fluorometric methods have been used to analyze trace amounts of D-amino
      acids in biological samples. In this study, we established an expedient column
      switching fluorometric HPLC system that would improve the analysis of D-amino
      acids, in particular D-aspartate (Asp). Our system consists of the fluorogenic
      derivatization of amino acids with NBD-F and two chromatographic steps, one that
      separates individual amino acids in reverse phase mode and another that separates
      the chiral forms of each amino acid in normal-phase mode. The two separation
      steps are linked through a trapping column by an automated column-switching
      system. In addition, sample preparation is simplified and improved, where
      trichloroacetic acid is used for deproteinization, and borate buffer, pH 9.5 is
      employed for the fluorescent derivatization. The detection limit for D-Asp in
      culturing medium is 5 nM. The resulting peak heights correlated well with
      concentrations that ranged from 12.5 to 250 nM for both D- and L-Asp. The present
      method was applied to determine D- and L-Asp levels in cell culturing medium, and
      within cells of MPT1 cell line. The detected cellular levels of D- and L-Asp
      agree with those detected by our previous method. In addition, this method was
      used to measure D- and L-Asp levels in rat blood samples, and the results are
      consistent with the reported values.

PMID- 11585138
TI  - Guidelines for the evaluation and management of traumatic dental injuries.

PMID- 11585139
TI  - Traumatic injuries to anterior teeth among schoolchildren in Malaysia.
AB  - Evidence of traumatized permanent incisors was recorded as part of a national
      oral health survey of schoolchildren in Malaysia. A total of 4,085 schoolchildren
      aged 16 years were examined. The prevalence of injury was 4.1% and it was
      significantly higher in males than females, with a ratio of 2:1. Almost 75% of
      the subjects had one tooth affected. Out of a total of 200 fractured teeth, 78.0%
      involved the maxillary central incisors. A high level of untreated traumatized
      teeth (89%) was noted. However, of the untreated traumatized teeth, only 9%
      presented with problems such as discoloration of tooth, sinus or abscess
      formation.

PMID- 11585140
TI  - Prevalence of dental trauma in 5-6- and 12-14-year-old boys in Riyadh, Saudi
      Arabia.
AB  - This study involved 354 boys aged 5-6 years and 862 boys aged 12-14 years,
      attending 40 schools in Riyadh. All children were examined at school by a single
      dental examiner, using criteria similar to those employed in the survey of
      children's dental health in the United Kingdom. The prevalence of dental trauma
      in 354 Saudi boys aged 5-6 years was 33%. The most common type of dental trauma
      was fracture of enamel (71%) followed by loss of tooth due to trauma (13%),
      fracture into enamel and dentine (7%), discolouration (5%), pulp involvement
      (4%). No relationship between the degree of overjet and the occurrence of dental
      trauma in the primary dentition was observed. The prevalence of dental trauma in
      862 12-14-year-old boys was 34%. The commonest dental trauma was fracture of
      enamel (74%) followed by fracture into enamel and dentine (15%), fracture into
      enamel-dentine and pulp (5%), loss of tooth due to trauma (3%), and
      discolouration (0.4%). A significant relationship (P=0.02) between the increased
      overjet (> or = 6 mm) and the occurrence of dental trauma in the permanent
      dentition was reported. The present study found no evidence of dental care
      provided for traumatised primary incisors in 5-6-year-old boys. The treatment of
      dental trauma in 12-14-year-old boys was negligible (2.4%). The present Saudi
      Arabian study showed higher prevalence of dental trauma in 5-6- and 12-14-year
      old boys than the reported results of the United Kingdom Children's Dental Health
      Survey of the same age groups.

PMID- 11585141
TI  - Effect of a consensus statement on initial treatment for traumatic dental
      injuries.
AB  - The aim of this study was to investigate the influence of a consensus statement
      on dental practitioners' choice of initial treatment for traumatic dental
      injuries. Dental practitioners working at government dental clinics in eight
      cluster sample regions of mainland Tanzania were requested to participate in the
      study; that is, to record the treatment they provided to children aged 1-17 years
      seeking dental consultation after injury for a period of 12 months. Six months
      after the beginning of data collection, a consensus statement was introduced.
      After the dental practitioners received the consensus statement, the correct
      treatment they provided increased from 51% to 57%. The unnecessary treatments
      increased from 54% to 59%, while wrong treatments decreased from 55% to 42%. Only
      a small improvement was observed in the percentage of correct treatments, but
      there was a slightly significant improvement in the percentage of wrong
      treatments provided before and after introduction of the consensus statement. We
      conclude that the consensus statement had a slight influence on the dental
      practitioners' choice of initial treatment for dental trauma in the desired
      direction.

PMID- 11585142
TI  - Response of the pulp of dogs to capping with mineral trioxide aggregate or a
      calcium hydroxide cement.
AB  - This study was conducted to observe the response of dogs' dental pulp to mineral
      trioxide aggregate (MTA) and a calcium hydroxide cement when used as pulp capping
      materials. After the pulps of 30 teeth were exposed, they were capped with either
      MTA or a calcium hydroxide cement. Histological analysis was performed 2 months
      after treatment. Results showed a healing process with complete tubular dentin
      bridge formation and no inflammation in any of the pulps capped with MTA. On the
      other hand, only five specimens from the calcium hydroxide cement group formed a
      complete dentin bridge. In this experimental group, pulp inflammation was
      observed in all but three cases. In conclusion, MTA exhibited better results than
      the calcium hydroxide cement for the capping of the pulp in dogs.

PMID- 11585143
TI  - Fracture resistance of human incisors and premolars: morphological and patho
      anatomical factors.
AB  - 305 extracted human front teeth and premolars were investigated for their dynamic
      resistance to fracture. Morphological factors, such as the anatomical class of
      tooth and root lengths, and patho-anatomical factors, such as infractions,
      occlusal and cervical abrasions, composite and amalgam restorations and damage
      resulting from previous traumatic impacts, were taken into consideration. A
      comparison of stability after a defined impact stress showed that maxillary
      canines and premolars had the highest resistance to fracture; this differs
      significantly from the resistance of maxillary and mandibular incisors. The root
      length correlates directly with fracture energy and therefore to stability.
      Composite restorations with an adhesive joint were found to increase the
      resistance of a tooth to fracture, but amalgam restorations had a weakening
      effect. Cervical wedge-shaped defects of the tooth cause considerable
      destabilization, but occlusal abrasion and infractions have only a moderate
      weakening influence. Previous traumatic stress reduces the resistance to fracture
      of a tooth by up to 85%. The fracture patterns generated were very similar to
      clinically observed tooth fractures, indicating the results to be clinically
      relevant.

PMID- 11585144
TI  - Periodontal healing after bonding treatment of vertical root fracture.
AB  - Vertical root fractures lead to advanced periodontal breakdown with deep
      periodontal pockets and vertical bone defects. The purpose of this study is to
      evaluate clinically the periodontal healing of root fracture treatment using
      adhesive resin cement. In 22 patients, 23 teeth with vertical root fractures were
      treated with 4-META/MMA-TBB resin cement. Eleven fractured roots were bonded
      through the root canal (group A) and 12 fractured roots were bonded extra-orally
      and replanted (group B). All teeth were then restored with full cast crowns
      (n=20) or coping (n=3). Mean probing depth was 6.6 mm at pre-treatment and 4.4 mm
      6 months after the treatment in group A, and 7.4 mm and 4.6 mm, respectively, in
      group B. Bleeding scores were 100% at pre-treatment and 36.4% after 6 months in
      group A and 91.7% and 8.3%, respectively in group B. Radiographic bone level was
      56.8% at pretreatment and 59.1% after 6 months in group A, and 18.8% and 29.2%,
      respectively, in group B. Two roots of group A and three roots of group B were
      extracted due to refracture, deterioration of periodontal inflammation, mobility,
      and luxation. The remaining roots (n=18) presented no discomfort to the patients
      and there was no deterioration of periodontal conditions over a mean period of 33
      months (range 14-74 months) in group A and over a mean period of 22 months (range
      6-48 months) in group B. There was no ankylosed teeth nor was any root resorption
      detected. The results suggested that the treatment of vertical root fracture
      using 4-META/MMA-TBB resin has good prognostic possibilities.

PMID- 11585145
TI  - Splinting of traumatized teeth with a new device: TTS (Titanium Trauma Splint).
AB  - Displacement injuries of permanent teeth are an increasing emergency in the
      dental office. Children and adolescents are particularly prone to dental trauma
      due to participation in risky activities. Repositioning or replantation with
      subsequent stabilization by a dental splint is the standard of care for most
      displaced or avulsed permanent teeth. Non-rigid fixation allowing physiologic
      tooth mobility has been shown to be desirable for periodontal healing. A flexible
      splint of short duration appears to reduce the risk of dentoalveolar ankylosis or
      external replacement resorption. Different splinting techniques are currently
      recommended for stabilization of repositioned or replanted teeth, including a
      wire-composite splint, an orthodontic bracket splint or a resin splint. Each
      splinting option has its specific advantages and shortcomings. This paper
      describes a new splinting technique which offers improved comfort and handling to
      the patient and dentist alike.

PMID- 11585146
TI  - Revascularization of an immature permanent tooth with  apical periodontitis and
      sinus tract.
AB  - A necrotic immature mandibular second premolar with periapical involvement in a
      13-year-old patient was treated. Instead of the standard root canal treatment
      protocol and apexification, antimicrobial agents were used in the canal, after
      which the canal was left empty. Radiographic examination showed the start of
      apical closure 5 months after the completion of the antimicrobial protocol.
      Thickening of the canal wall and complete apical closure was confirmed 30 months
      after the treatment, indicating the revascularization potential of a young
      permanent tooth pulp into a bacteria-free root canal space.

PMID- 11585147
TI  - Auto-alloplastic transplantation of a primary canine after traumatic loss of a
      permanent central incisor.
AB  - This report describes the transplantation of a primary canine after traumatic
      loss of a central incisor in an 8-year-old boy. The 7-month follow-up revealed
      normal periodontal healing with absence of infection, ankylosis or progressive
      resorption. The patient was then lost for control. After 16 months another trauma
      in the same patient resulted in an avulsion of the transplant. However, the
      alveolar bone was maintained in vertical and sagittal dimensions. Another primary
      canine was transplanted and followed for further 11 months. Again normal
      periodontal healing could be observed. The transplantation of a primary canine is
      seen as a promising method to replace a lost permanent tooth and maintain the
      surrounding tissues in very young patients.

PMID- 11585148
TI  - ICF approved as the successor of ICIDH.

PMID- 11585149
TI  - Knee muscle activity during ambulation of trans-tibial amputees.
AB  - Gait analysis of trans-tibial amputees brings to light asymmetries of different
      gait parameters between the amputated and sound legs. The present study
      investigated the activity of the vastus medialis and biceps femoris muscles
      during ambulation of trans-tibial amputees. Peak activities of the vastus
      medialis were reached similarly in both legs (6.06+/-4.9% and 8.84+/-3.6% of gait
      cycle, in the sound and amputated leg, respectively). Biceps femoris peak
      activities were reached at 92.43+/-6.6% of gait cycle in the sound leg, and
      significantly later (at 9.81+/-4.8% of gait cycle) in the amputated leg (p <
      0.05). Integrated EMG activity ratios, between swing and stance periods, were
      similar for the vastus medialis (0.33 in the sound and 0.35 in the amputated
      leg). However, these ratios differed significantly for the biceps femoris since
      the amputated leg presented a substantial (p < 0.05) smaller ratio (0.22)
      compared with the sound leg (0.83). The use of prosthesis in trans-tibial
      amputees requires further activity of the biceps femoris during stance period to
      improve support of the amputated leg knee joint.

PMID- 11585150
TI  - Physical training with and without oxygen in patients with chronic obstructive
      pulmonary disease and exercise-induced hypoxaemia.
AB  - A randomized, controlled, single-blind study was performed on 20 patients with
      chronic obstructive pulmonary disease and exercise-induced hypoxaemia. Ten
      patients each were randomly assigned to one of two groups, one training with air
      and the other training with oxygen. There were no significant differences between
      the groups regarding values measured prior to the study. The patients trained 3
      times per week for 30 minutes each time for a duration of 8 weeks. The training
      consisted of interval walking on a treadmill (intensity set according to Borg
      ratings) with either air or oxygen administered through a nasal cannula at a rate
      of 5 l/min. Training significantly improved the 6-minute walking distance by 20%
      and 14% in the air and oxygen group, respectively, when the patients were tested
      on air. In the same test the air group significantly decreased Borg ratings for
      perceived exertion. Borg ratings for dyspnoea and perceived exertion
      significantly decreased in the oxygen group when they were tested on oxygen. It
      was concluded that oxygen supplementation did not further improve the training
      effect, compared with training with air, in patients with chronic obstructive
      pulmonary disease and exercise-induced hypoxaemia.

PMID- 11585151
TI  - Activities of daily living and quality of life in persons with muscular
      dystrophy.
AB  - The study concerns 77 adults with muscular dystrophy (mean age 49 years) in two
      counties in Sweden. The purpose was to investigate activities of daily living,
      quality of life and the relationship between these. Data collection was performed
      with "the Activity of Daily Living Staircase", "the Self-report Activity of Daily
      Living" and the Quality of Life Profile. The results indicated that over half of
      the subjects were dependent on others, chiefly in activities requiring mobility.
      Muscular dystrophy had mostly negative consequences, and nearly half stated that
      life would have offered more without it. Few significant diagnosis-related (no
      gender-related) differences emerged regarding activities of daily living and
      quality of life. Lower quality of life can only partly be explained by greater
      disability (r=0.30-0.54). Therefore quality of life as a measurement of
      rehabilitation outcomes might be based both on physical status, disability and
      psychosocial factors in terms of positive and negative consequences.

PMID- 11585152
TI  - Therapeutic ultrasound: temperature increase at different depths by different
      modes in a human cadaver.
AB  - A specific increase in temperature is necessary to achieve a temperature-mediated
      therapeutic impact by ultrasound in rehabilitation. In order to obtain a physical
      basis for a definite temperature rise at a certain depths in the human body a
      human cadaver study in situ was conducted. A set of 16 experiments was carried
      out with an ultrasound frequency of 1 and 3 MHz. For each frequency the pulsed
      and continuous mode of energy delivery were compared at a variable intensity of
      0.5, 1.0, 1.5 and 2.0 W/cm2. The ultrasonic energy was delivered in direct
      contact to the cadaver at the posterior crural compartment of the leg in a static
      manner. Temperature was monitored with a 1-minute interval during an insonation
      of 10 minutes. Results revealed that theoretical physical predictions concerning
      tissue heating by therapeutic ultrasound could not always be consolidated and
      that thermal therapeutic effects for deeper conditions are not obvious to be
      achieved by ultrasonic therapy.

PMID- 11585154
TI  - Evaluation of grip strength with a sustained maximal isometric contraction for 6
      and 10 seconds.
AB  - The grip strength in which subjects sustained a maximal isometric contraction for
      6 seconds (the 6-second test) was compared with that for 10 seconds (the 10
      second test) to clarify a reliable sustained grip strength test procedure. Fifty
      healthy students (22+/-4 years, 25 men and 25 women) participated in this study.
      Strength was measured continuously by the Dexter (Cedaron Medical Inc.). The
      maximal grip strength, the peak time, and the momentary strength every second
      during a trial were evaluated. For both tests, the reliable maximal strength and
      a typical strength-time curve consisting of an early peak time and a decrease in
      the strength after the peak gradually over time were obtained. In the 6-second
      test, the momentary strength after 5 seconds that was 82+/-10 approximately 87+/
      7% of the peak strength showed good reliability. This variable may be effective
      in assessing the ability to sustain maximal grip strength.

PMID- 11585153
TI  - Women at work despite ill health: diagnoses and pain before and after personnel
      support. A prospective study of hospital cleaners/home-help personnel with
      comparison groups.
AB  - The present study sought to elicit the diagnoses behind the pain conditions
      causing complaints by female hospital cleaners and home-help personnel who were
      working despite their symptoms. We also wished to describe the prevalence of
      musculoskeletal diagnoses and the intensity, frequency and location of pain, and
      changes in the clinical picture and pain after personnel supporting
      interventions. A prospective study was carried out with intervention groups and
      non-randomized comparison groups. The hospital cleaners intervention programme
      comprised occupational organizational measures, competence development, physical
      and psychosocial working environmental measures and individual and rehabilitation
      measures on both an individual and a group basis. The home-help programme
      comprised a 2-week stay at an orthopaedic rehabilitation unit, training of
      supervisors, comrade massage, purchase of training equipment and stress
      management. Myalgia/ tendinitis occurred in 61% of shoulder girdle elevators, 18%
      of rotator cuffs, 16% of dorsal neck muscles and 29% of hip muscles. There was
      musculoskeletal pain in the lower back in 28% of cases. Referred pain from a
      musculoskeletal focus occurred in about one-sixth to one-third of individuals
      with the diagnosis in question. Neurogenic pain occurred in 6% of cases. No
      fibromyalgia syndrome was found. One-third of individuals felt pain all the time
      or almost all the time. The mean rated perceived "worst pain" was 70 mm on a
      visual analogue scale of 1-100 mm. Comparisons between intervention and reference
      groups indicated that some improvement in the clinical picture can be attained
      using this kind of general support programme for employees.

PMID- 11585155
TI  - Modulation of corticospinal excitability during imagined knee movements.
AB  - In this study, we investigated corticospinal excitability during mental
      simulation of a leg extension movement with the technique of transcranial
      magnetic stimulation. Motor evoked potentials were recorded in both knee
      extensors (quadriceps) and flexors (biceps femoris) in 19 trained participants
      (healthy volunteers). The amplitude and latency of motor evoked potentials were
      compared in three conditions: (1) at rest, (2) during motor imagery, and (3) at
      rest, immediately after motor imagery. The results showed a significant effect (p
      < 0.001) of conditions on motor evoked potentials amplitude in the quadriceps but
      not in the biceps femoris. During motor imagery, the size of motor evoked
      potentials in the quadriceps increased significantly (p < 0.001) compared with
      rest and post-imagery conditions. Changes in motor evoked potentials latency
      across conditions were not significant, however. These results are consistent
      with previous studies in the upper limb and suggest that corticospinal
      excitability can be enhanced during motor imagery to facilitate responses in
      specific lower limb muscles.

PMID- 11585156
TI  - Augmentative and alternative communication methods in locked-in syndrome.
AB  - Locked-in syndrome is a neurological condition due to a brain disease or an
      injury affecting the brain stem. The symptoms are tetraplegia, double-sided
      facial paresis, anarthria/dysarthrophonia, dysphagia and reactive involuntary
      laughing and crying. Vertical eye movements are the only commonly remaining
      voluntary motor function. Although the linguistic abilities as well as
      intellectual and emotional functions as a whole remain intact, all the motor
      abilities of self expression are lost. Seventeen chronic locked-in syndrome
      patients referred to Kapyla Rehabilitation Centre between 1979-2000 are reported.
      The multidisciplinary rehabilitation team developed an individual alternative
      communication method for all patients and trained them to use it by minor
      movements of e.g. thumb, chin or head. An alternative communication method
      enabled most of the patients to interact with other people using practical as
      well as theoretical thinking and decision making.

PMID- 11585157
TI  - The public versus the World Health Organization on health system performance.
AB  - The World Health Organization (WHO) ranked health systems in 191 countries based
      on measures developed by public health experts. This paper compares the WHO
      rankings for seventeen industrialized countries with the perceptions of their
      citizens. The results show little relationship between WHO rankings and the
      satisfaction of the citizens who experience these health systems. The health
      systems of some top WHO performers are rated poorly by their citizens, including
      the low-income and elderly. The two rated most highly by the public rank at the
      bottom of the WHO ratings. These findings suggest that both public and expert
      views should be considered in international rankings.

PMID- 11585158
TI  - A cost-effectiveness approach to drug subsidy and pricing in Australia.
AB  - The Australian government offers its citizens subsidies on a select list of
      pharmaceuticals. For a drug to qualify for inclusion on this list, its
      manufacturer must demonstrate that the drug is both clinically effective and cost
      effective. In part, this measure, along with others, was introduced to improve
      clinical and economic outcomes. Although this evidence-based system has provided
      transparency and consistency in decision making about which drugs will be
      covered, it may not have contained the rate of increase in drug costs.

PMID- 11585159
TI  - Primary care in Canada: so much innovation, so little change.
AB  - The development of Canadian primary care has been shaped by a series of policy
      legacies that continue to affect the possibilities for change in primary care
      through their cumulative effects on the health care system and the process of
      health policy development. The pursuit of radical systemwide change in the face
      of unfavorable circumstances (created in large part by those legacies) has
      resulted in missed opportunities for cumulative incremental change. While major
      changes in primary care policy seem unlikely in the near future, significant
      incremental change is possible, but it will require a reorientation of the policy
      development process.

PMID- 11585160
TI  - Primary care groups in the United Kingdom: quality and accountability.
AB  - With the introduction of primary care groups (PCGs), the British National Health
      Service has attempted to integrate delivery, finance, and quality improvement
      into a locally directed care system with a strong sense of community
      accountability. PCGs will eventually hold the budgets for primary care,
      specialist, hospital, and community-based services and have the flexibility to
      reapportion these budgets. Through clinical governance, PCGs are attempting to
      coordinate education, guidelines, audit and feedback, and other quality
      improvement approaches around health problems that are relevant to their patient
      panels and local communities. PCGs offer other nations attempting to improve the
      quality and accountability of health care an innovative approach that merits
      consideration.

PMID- 11585161
TI  - An activist health minister in a conservative government.

PMID- 11585162
TI  - Promoting private health insurance in Australia.
AB  - Health insurance policy in Australia has been distinguished by considerable
      instability over the past five years. This paper reviews the rationale and
      emerging evidence on three major policy initiatives--a move to allow selective
      contracting, the introduction of a 30 percent government subsidy for private
      health insurance, and the abolition of pure community rating. Policy making on
      private health insurance has been characterized by insufficient attention to
      research that might provide a stronger evidence basis for policy reforms.

PMID- 11585163
TI  - For-profit and not-for-profit health plans participating in Medicaid.
AB  - The proliferation of for-profit health plans has heightened concerns about
      quality of care, particularly with respect to Medicaid. We undertook this study
      to compare for-profit and not-for-profit health plans that participate in
      Medicaid, examining processes of care and the organizational characteristics
      related to utilization management, financial incentives, and quality of care. Our
      findings demonstrate that for-profit and not-for-profit plans appear to be more
      similar than dissimilar in many areas of management, although for-profit plans
      are more likely to use aggressive utilization review and have slightly less
      developed quality management systems. On balance, these findings should reassure
      critics of for-profit health care.

PMID- 11585164
TI  - Beyond managed long-term care: paying for home care based on risk of adverse
      outcomes.
AB  - Evaluations of home care for chronically ill elderly people have shown
      disappointing results for many years. Improvements in outcomes have been slight
      and costs high. We offer a system for setting budget targets based upon
      effectiveness of home care in mitigating certain adverse outcomes, the risk of
      those outcomes those outcomes. We believe that such a budgeting system will
      encourage improved measurement of outcomes and more rigorous justification for
      expenditures. Moreover, such a system is designed to reallocate resources to
      higher-risk patients and those more likely to benefit, focusing caregiving on
      specific outcomes and improving those outcomes.

PMID- 11585165
TI  - Corporate health care purchasing among Fortune 500 firms.

PMID- 11585166
TI  - Medicare home health before and after the BBA.

PMID- 11585167
TI  - Is the informed-choice policy approach appropriate for Medicare beneficiaries?

PMID- 11585168
TI  - Providing care at the end of life: do Medicare rules impede good care?

PMID- 11585169
TI  - People's experience versus people's expectations.

PMID- 11585170
TI  - La promotora. Linking disenfranchised residents along the border to the U.S.
      health care system.

PMID- 11585171
TI  - Comparing health system performance in OECD countries. Organization for Economic
      Cooperation and Development.
AB  - We present data from the Organization for Economic Cooperation and Development
      and the World Health Organization on the performance of the health care systems
      in twenty-nine industrialized countries in 1998. We also compare the performance
      of the United States with the other industrialized countries for selected
      indicators in 1960, 1980, and 1998. On most indicators the U.S. relative
      performance declined since 1960; on none did it improve.

PMID- 11585172
TI  - Physicians' views on quality of care: a five-country comparison.
AB  - Interest is resurging in the problems relating to the quality of patient care.
      This paper provides a comparative perspective on this issue from a five-country
      physician survey conducted in Australia, Canada, New Zealand, the United Kingdom,
      and the United States in 2000. Physicians in all five countries reported a recent
      decline in quality of care and concerns with how hospitals address medical
      errors. Physicians in four countries expressed serious concerns about shortages
      of medical specialists and inadequate facilities. U.S. physicians reported
      problems caused by patients' inability to pay for prescription drugs and medical
      care. Asked about efforts to improve quality of care in the future, physicians
      indicated support for electronic medical records, electronic prescribing, and
      initiatives to reduce medical errors.

PMID- 11585173
TI  - Patients' experiences with hospital care in five countries.
AB  - Analysis of patient surveys carried out in Germany, Sweden, Switzerland, the
      United Kingdom, and the United States in 1998-2000 revealed high rates of
      problems during inpatient hospital stays. Problems with information and
      education, coordination of care, respect for patients' preferences, emotional
      support, physical comfort, involvement of family and friends, and continuity and
      transition were prevalent in all five countries. These dimensions of patients'
      experience appear to be salient and relevant in each of the five countries, but
      attempts to develop international rankings based on this type of evidence will
      have to overcome a number of methodological problems.

PMID- 11585174
TI  - Technological change around the world: evidence from heart attack care.
AB  - Although technological change is a hallmark of health care worldwide, relatively
      little evidence exists on whether changes in health care differ across the very
      different health care systems of developed countries. We present new comparative
      evidence on heart attack care in seventeen countries showing that technological
      change--changes in medical treatments that affect the quality and cost of care-
      is universal but has differed greatly around the world. Differences in treatment
      rates are greatest for costly medical technologies, where strict financing limits
      and other policies to restrict adoption of intensive technologies have been
      associated with divergences in medical practices over time. Countries appear to
      differ systematically in the time at which intensive cardiac procedures began to
      be widely used and in the rate of growth of the procedures. The differences
      appear to be related to economic and regulatory incentives of the health care
      systems and may have important economic and health consequences.

PMID- 11585175
TI  - Risk sharing between competing health plans and sponsors.
AB  - In many countries, competing health plans receive capitation payments from a
      sponsor, whether government or a private employer. All capitation payment methods
      are far from perfect and have raised concerns about risk selection. Paying health
      plans partly on the basis of capitation and partly on the basis of actual costs
      ("risk sharing") reduces plans' incentives for selection but sacrifices some
      incentives for efficiency. This paper summarizes our empirical research on Dutch
      health plans with respect to various forms of risk sharing. All sponsors can
      improve their payment systems by either implementing or changing their form of
      risk sharing.

PMID- 11585176
TI  - Racial/ethnic disparities in nursing.
AB  - The racial and ethnic composition of the registered nurse (RN) workforce in
      California is not at parity with the composition of the population. We find that
      the underrepresentation of African Americans in nursing in California appears to
      be due to lower overall educational attainment among African Americans.
      Underrepresentation of Latinos is due to lower overall educational attainment
      and, to a lesser extent, a lower percentage of college-educated Latinos pursuing
      careers in nursing. Improving the overall educational attainment of minority
      students is critical to increasing the number of minorities in nursing.

PMID- 11585177
TI  - Faith in action: building capacity for interfaith volunteer caregiving.

PMID- 11585178
TI  - Second-choice health reform not good enough.

PMID- 11585179
TI  - Tax credits for both job-based and individual coverage.

PMID- 11585180
TI  - Reflecting on Donabedian's legacy.

PMID- 11585182
TI  - Quality of care for coronary heart disease in two countries.
AB  - Coronary heart disease is the leading cause of death in the United States and
      England, and each country devotes substantial resources to its prevention and
      treatment. We review recent strategies for improving quality of care for coronary
      heart disease in each country, including clinical guidelines; national standards;
      performance reports; benchmarking, feedback, and professional leadership; and
      market-oriented approaches. These strategies highlight the importance of
      information systems, organizational culture, and incentives to improve the
      quality of care in both the decentralized health care system of the United States
      and England's more centralized system.

PMID- 11585181
TI  - Nurses' reports on hospital care in five countries.
AB  - The current nursing shortage, high hospital nurse job dissatisfaction, and
      reports of uneven quality of hospital care are not uniquely American phenomena.
      This paper presents reports from 43,000 nurses from more than 700 hospitals in
      the United States, Canada, England, Scotland, and Germany in 1998-1999. Nurses in
      countries with distinctly different health care systems report similar
      shortcomings in their work environments and the quality of hospital care. While
      the competence of and relation between nurses and physicians appear satisfactory,
      core problems in work design and workforce management threaten the provision of
      care. Resolving these issues, which are amenable to managerial intervention, is
      essential to preserving patient safety and care of consistently high quality.

PMID- 11585183
TI  - Foreign lessons: is there value added?

PMID- 11585184
TI  - Improving quality, minimizing error: making it happen.
AB  - Medical errors and the quality problems to which they lead harm millions of
      Americans each year. If we are to reduce errors and improve quality
      substantially, we must create systems and care processes that anticipate
      inevitable human errors and either prevent them or compensate for them before
      they cause harm. Formidable barriers now stand in the way of progress. Success
      will require a multifaceted strategy, including public education, government
      investment and regulation, payment system restructuring, and leadership from
      within the delivery system.

PMID- 11585185
TI  - Keeping quality on the policy agenda.
AB  - Quality of care in the United States and elsewhere consistently fails to meet
      established standards. These failures subject patients to premature death and
      needless suffering. Yet, unlike the experience with other threats to life (tire
      failures or airplane rudders), public and private policymakers have been unable
      to maintain sufficient interest in identifying and solving problems with quality
      to change the way in which care is delivered. We discuss why it is hard to keep
      quality on the policy agenda and suggest short-term steps that are necessary if
      quality is to improve here and in the rest of the world.

PMID- 11585186
TI  - Pharmaceutical cost control in Canada: does it work?
AB  - Governments in Canada have instituted mechanisms intended to control drug prices.
      These include the establishment of a semi-judicial body by the federal government
      to control factory-gate prices and of various measures at the provincial level,
      such as formulary management, use of generics, reference-based pricing, price
      freezes, and limits on markups. To a large extent, these measures have been
      effective in price control. Total drug spending in the country continues to rise,
      however; clearly, mechanisms other than price controls will need to be developed
      if drug spending is to be better managed.

PMID- 11585187
TI  - Informed consent from the community?

PMID- 11585188
TI  - What do we need for robust, quantitative health impact assessment?
AB  - Health impact assessment (HIA) aims to make the health consequences of decisions
      explicit. Decision-makers need to know that the conclusions of HIA are robust.
      Quantified estimates of potential health impacts may be more influential but
      there are a number of concerns. First, not everything that can be quantified is
      important. Second, not everything that is being quantified at present should be,
      if this cannot be done robustly. Finally, not everything that is important can be
      quantified: rigorous qualitative HIA will still be needed for a thorough
      assessment. This paper presents the first published attempt to provide practical
      guidance on what is required to perform robust, quantitative HIA. Initial steps
      include profiling the affected populations, obtaining evidence for postulated
      impacts, and determining how differences in subgroups' exposures and
      susceptibilities affect impacts. Using epidemiological evidence for HIA is
      different from carrying out a new study. Key steps in quantifying impacts are
      mapping the causal pathway, selecting appropriate outcome measures and selecting
      or developing a statistical model. Evidence from different sources is needed. For
      many health impacts, evidence of an effect may be scarce and estimates of the
      size and nature of the relationship may be inadequate. Assumptions and
      uncertainties must therefore be explicit. Modelled data can sometimes be tested
      against empirical data but sensitivity analyses are crucial. When scientific
      problems occur, discontinuing the study is not an option, as HIA is usually
      intended to inform real decisions. Both qualitative and quantitative elements of
      HIA must be performed robustly to be of value.

PMID- 11585189
TI  - Estimating health needs: the impact of a checklist of conditions and quality of
      life measurement on health information derived from community surveys.
AB  - BACKGROUND: Prevalence estimates of chronic disease vary according to the
      technique used. Questionnaire surveys may be susceptible to inaccuracies, which
      may be overcome by addition of a checklist of conditions. This paper presents SF
      36 scores and NHS consultation rates for people reporting individual chronic
      diseases or disabilities in two questionnaire surveys, one of which employed a
      checklist and one of which did not. We aimed to document differences in estimates
      of disease prevalence, and to determine whether or not subjective impact on
      quality of life is the same in people recruited by a checklist as in those who
      volunteer that they have a chronic disease or disability without the prompt of a
      checklist. We use these data to estimate the contribution that different chronic
      diseases and disabilities make to the burden of disease in the community.
      METHODS: Data were collected in two postal questionnaire surveys conducted in
      1991 and 1997 with response rates of 72 per cent and 64 per cent. Both
      questionnaires included a question on long-standing illness, disability or
      infirmity, together with the SF-36 health status measure. Respondents to the 1991
      survey were asked to specify their illness in a free text response, whereas the
      1997 survey offered a checklist of conditions. Prevalence rates of each condition
      were calculated, together with an 'escalation factor' representing the increase
      in reporting of specific diseases between the surveys. SF-36 domain and component
      summary scores were calculated overall and for the groups reporting individual
      chronic diseases or disabilities. Disease-specific NHS consultation rates were
      calculated for both surveys. RESULTS: The overall reported rate of chronic
      disease and disability increased from 28 per cent in 1991 to 42 per cent in 1997.
      Reported levels of mental health problems and of conditions with a perceived
      psychosomatic element increased substantially, whereas rates of well-defined
      conditions were similar. The pattern of SF-36 scores for those reporting chronic
      disease or disability was similar in the two surveys in spite of very different
      prevalence rates, and respondents reporting chronic disease had similar levels of
      health service use. This suggests that they were reporting conditions with
      similar levels of impact on quality of life. Heart disease, arthritis and mental
      health problems had the greatest impact on quality of life, and asthma and
      hypertension the least. CONCLUSIONS: Evidence from SF-36 scores and NHS
      consultation rates suggests that addition of a checklist of conditions to this
      community health survey encouraged reporting of illnesses by the genuinely ill
      and not merely by those who are less severely affected by their disease. This
      method appears to give a more accurate reflection of health needs than
      information derived from routine data sources. The combination of prevalence data
      combined with subjective assessment of quality of life allows an alternative
      perspective of health needs. This approach highlights the relative importance of
      musculo-skeletal problems, particularly back pain, and mental health problems to
      the burden of disease, and the relative lack of importance of conditions such as
      asthma. It presents a contrast to studies based on other methods of health needs
      assessment.

PMID- 11585190
TI  - An assessment of the construct validity of the SF-12 summary scores across ethnic
      groups.
AB  - BACKGROUND: The aim of the study was to determine the construct validity of the
      12-item Short Form health survey questionnaire (SF-12) across ethnic groups in a
      large community sample of the United Kingdom. METHODS: A postal survey was
      carried out in English using a questionnaire booklet, containing the SF-12 and a
      number of other items relating to experiences of chronic illness and utilization
      of health care services. The dataset was the National Survey of NHS Patients. The
      sample consisted of 1000 residents within each Health Authority in England who
      were randomly selected from the electoral registers, giving an initial sample of
      100000. RESULTS: A total of 61 426 (61.4 per cent) questionnaires were returned;
      94.3 per cent of respondents classified themselves as white and 5.7 per cent
      classified themselves as members of other ethnic groups. Construct validity of
      the SF-12 was assessed by comparing results from the two summary scores (the
      Mental Health Component Summary (MCS) score and the Physical Health Component
      Summary (PCS) score) with overall self-assessed health and limiting longstanding
      illness. Although there were generally consistent patterns of association between
      overall self-assessed health or limiting longstanding illness and the MCS and PCS
      scores in all the ethnic groups, there were significant differences between the
      MCS and PCS scores of Indians, Pakistanis and Bangladeshis who understood English
      fluently and those who did not. Furthermore, there were differences in the
      completion rates of the SF-12 between ethnic groups and a reversal of the general
      pattern of increasing MCS scores with increasing age in Bangladeshis. CONCLUSION:
      The results indicate that the use of the SF-12 to measure the health of ethnic
      minorities seems acceptable in most instances, but may prove problematic in those
      instances where respondents complete the questionnaire via an untrained
      translator, such as a friend or family member. The systematic differences in MCS
      and PCS scores between ethnic minorities who understood English fluently and
      those who did not suggest that the meaning of specific SF-12 items may change
      when informally translated. Future research using the SF-12 to measure the health
      status of ethnic minorities in the United Kingdom via postal surveys must include
      questions on whether respondents completed the questionnaires via informal
      translations. In general, those wishing to measure the health of members of
      ethnic groups who are unable to read English might consider using different
      techniques to gain the information from these groups.

PMID- 11585191
TI  - Commercially available folic acid supplements and their compliance with the
      British Pharmacopoeia test for dissolution.
AB  - A recent report suggested that some folic acid preparations available in the
      United States failed to meet the specifications for dissolution specified by the
      US Pharmacopoeia (USP), of 70 per cent drug release in the first hour of testing.
      The Teratology Society recommends that women of childbearing age should take a
      daily supplement of 400 microg folic acid when they are trying to conceive, to
      reduce the risk of foetal neural tube defects. The consequence of this failure to
      meet the USP requirements may be that an inadequate dose of folate may be
      absorbed and thus the expected level of protection against neural tube defects
      not afforded. The purpose of the present study was to examine a number of brands
      of folic acid (400 microg), available commercially in the United Kingdom, for
      compliance with the British Pharmacopoeia (BP) test for dissolution. Ten tablets
      (or capsules) from each of 11 brands were tested using dissolution apparatus
      compliant with BP requirements, using 0.1 M sodium hydroxide as the dissolution
      medium. The results indicated that four of the brands failed to release 70 per
      cent of the nominal drug content in the first hour of test and thus did not
      comply with the test. Two of the seven brands that passed the test went on to
      release more than 150 per cent of the nominal 400 microg drug content. These
      results highlight the problems of dose uniformity and the potential health risks
      of slow dissolution and under-dosing in commercially available folic acid dosage
      forms.

PMID- 11585192
TI  - Health care needs assessment in prisons: a toolkit.
AB  - BACKGROUND: Since 1999, prison health services and health authorities have been
      jointly responsible for assessing the health care needs of the prison population.
      To facilitate this process, the Department of Public Health and Epidemiology at
      the University of Birmingham developed a toolkit for carrying out a health care
      needs assessment of the prison population. METHODS: This paper describes the
      principles of the epidemiological approach to needs assessment and presents a
      stepped approach to carrying out a health care needs assessment in prisons. Some
      examples of the kind of health care needs to be found in prisons are presented.
      RESULTS: A systematic approach to the assessment of the health care needs of
      prisoners ensures that all the essential components of this important planning
      exercise are considered. The prison population is described, health problems are
      identified and quantified, and a review of current services is carried out. This
      allows the most effective solutions to addressing the health problems to be
      established. The process can be time consuming and is reliant on good data
      sources, but it does ensure that health problems and service elements are
      considered and addressed together rather than in a disjointed manner. CONCLUSION:
      The stepped approach to epidemiological needs assessment allows health problems
      and current services to be identified. It also allows these to be matched to
      appropriate service requirements.

PMID- 11585193
TI  - A systematic review of discharge coding accuracy.
AB  - BACKGROUND: The aim of the study was to review systematically the literature
      measuring the accuracy of routine UK hospital statistics that classify patients
      on discharge. METHODS: A systematic review was carried out of studies comparing
      routine discharge statistics about an episode of hospital care with the original
      medical record. Dual quality assessment and extraction was completed for included
      studies. Qualitative and descriptive analyses were undertaken. Additional
      comparisons of factors that could potentially introduce systematic variation in
      coding accuracy were also undertaken. RESULTS: Thirty studies were identified, of
      which 21 were included in the review. Twelve of these were conducted in England
      and Wales, and nine in Scotland. The majority assessed the accuracy of a single
      diagnosis, or selection of diagnoses in a limited range of hospital settings. The
      median coding accuracy rates were 91 per cent for diagnostic codes and 69.5 per
      cent for operation or procedure codes in studies in England or Wales; 82 per cent
      for diagnostic codes and 98 per cent for operation or procedure codes in Scottish
      studies. There were no significant differences in coding accuracy over time or in
      the type or rarity of the codes being assessed. Accuracy rates were higher for
      ICD7 codes (median 96.5 per cent) than for ICD8 (median 87 per cent) or ICD9
      (median 77 per cent). CONCLUSIONS: Coding accuracy on average is high in the
      United Kingdom, especially for operations and procedures. However, policy-makers,
      planners and researchers need to recognize and account for the degree of
      inaccuracy in routine hospital information statistics. Further research is needed
      into methods of improving and maintaining coding accuracy.

PMID- 11585194
TI  - Application of COMEAP dose-response coefficients within a regulatory health
      impact assessment methodology. Committee on the Medical Effects of Air
      Pollutants.
AB  - It is recognized that exposure to airborne pollutants can have a negative effect
      on human health. The Environment Agency in England and Wales has a statutory
      responsibility under the Environment Act 1990 to regulate emissions to air from
      large industrial processes with regard to the requirements of the National Air
      Quality Strategy (NAQS). A technique was developed to apply pollutant dose
      response relationships published by the Committee on the Medical Effects of Air
      Pollutants (COMEAP) in a regulatory framework, incorporating long-term sulphur
      dioxide concentration values obtained using an air dispersion model. Modelled
      long-term average sulphur dioxide concentration values for 102 electoral wards
      comprising an exposed area surrounding a hypothetical industrial stack emission
      in southern England were incorporated into a human health impact assessment using
      COMEAP dose-response relationships and annual baseline health data. Additional
      numbers of deaths brought forward and respiratory hospital admissions per annum
      resulting from the hypothetical sulphur dioxide emission were estimated. A second
      calculation using monthly baseline health data and monthly averaged concentration
      values was carried out to assess the sensitivity of the estimate of health impact
      to seasonal variability of baseline health and modelled average concentration
      datasets. The annual incremental impact varied by 1.49 per cent between the
      'annual' and 'sum of 12 months' analyses, suggesting that annual averaged
      modelled concentration values and annual baseline health data are sufficient for
      use in regulatory health impact assessments for large industrial processes using
      the COMEAP approach.

PMID- 11585195
TI  - The effect of physical activity advice given in routine primary care
      consultations: a systematic review.
AB  - BACKGROUND: Recent evidence and recommendations suggest that physical activity
      health promotion should be aimed at persuading the whole population to adopt an
      active lifestyle. Intensive medical programmes aimed at promoting physical
      activity amongst those at risk are not effective at achieving this aim. Brief
      advice from primary care professionals to quit smoking has a small but, at a
      population level, important effect. Brief advice in primary care to adopt a more
      active lifestyle may be similarly effective. The aim of this review is to
      determine the effect of advice given in routine primary care consultations on
      levels of physical activity. METHODS: A systematic review was carried out of
      trials assessing the effectiveness of advice given in routine primary care
      consultations. Data sources were four electronic databases (MEDLINE, EMBASE,
      Sport discus, Cochrane Library), and bibliographies of retrieved papers were
      searched. Experts were contacted. RESULTS: Eight trials, with a total of 4747
      participants, were identified; the majority were from the United States. Outcome
      measures varied considerably between trials, including continuous measures (e.g.
      duration of exercise) and dichotomous measures (e.g. being active), therefore
      statistical pooling was inappropriate. Two of the trials were cluster randomized
      controlled trials, the remainder were quasi-experimental. None of the trials
      fulfilled all of the predetermined quality criteria and selection bias in the
      nonrandomized studies may have exaggerated results. Four of the six trials that
      presented short-term (up to 8 weeks) results found advice to be effective; only
      one of the four trials with long-term follow-up (4-12 months) found a sustained
      effect. The two randomized controlled trials had negative short- and long-term
      results. CONCLUSIONS: From the available evidence it appears that advice in
      routine primary care consultations is not an effective means of producing
      sustained increases in physical activity. However, these results may not be
      applicable to the United Kingdom, where the structure of primary care is unique.
      Quality research in UK primary care would be valuable.

PMID- 11585196
TI  - Effective methods of giving information in cancer: a systematic literature review
      of randomized controlled trials.
AB  - There is increasing evidence to suggest that patients with cancer require more
      information about their disease and its consequences than they receive. In an
      attempt to address these needs, a variety of methods have been used to facilitate
      the passage of information from health professionals and other cancer information
      sources to cancer patients and their families. These include written material,
      telephone help-lines, teaching and audiovisual aids. Although these efforts have
      been well received, little attention has been given to the effectiveness of the
      methods employed. The aims of this paper were to systematically review randomized
      controlled trials that have evaluated methods of information-giving to cancer
      patients and their families. Relevant literature was identified through
      computerized databases, Internet cancer sites and bibliography searches. Multiple
      reviewers independently analysed the methodological quality of the papers
      according to agreed criteria. From this process, 10 studies were identified.
      Interventions ranged from written information to audiotapes, audiovisual aids and
      interactive medium. Individually tailored methods such as patient care records
      and patient educational programmes were also reviewed. The evidence indicated
      that the interventions had positive effects on a number of patient outcomes, such
      as knowledge and recall, symptom management, satisfaction, preferences, health
      care utilization and affective states. This was above and beyond the usual care
      provision. In the majority of studies the interventions had no effect on
      psychological indices. Furthermore, the review highlighted that certain methods
      should be based on individual preferences for information rather than uniformly
      administered.

PMID- 11585197
TI  - Some consequences of ancient mining activities on the health of ancient and
      modern human populations.
AB  - Heavy metal pollutants generated by mining activities in the Jordanian desert c.
      2000 years ago will have had detrimental effects on the health of slaves, guards
      and expert overseers. The pollutants continue to persist and cycle in the modern
      environment and affect plants, animals and inevitably the humans who are
      dependent on both. These findings have implications in terms of the public health
      of human populations living on or in the vicinity of ancient industrial sites
      around the Mediterranean and in the Middle East. Some effects of heavy metals on
      human health are examined; issues of bioaccumulation and partitioning are
      addressed.

PMID- 11585198
TI  - Winter excess morbidity: is it a summer phenomenon?
AB  - BACKGROUND: It was hypothesized that winter excess mortality is a feature of ill
      health produced by exposure to ambient low temperatures, and will be matched by
      winter excess morbidity. The aim of the study was to test the prediction that
      winter excess morbidity would be observable and would show a social class
      gradient with greater excesses in less affluent groups, who are less able to heat
      their houses or whose lack of a car exposes them more frequently to outdoor cold
      exposure. METHODS: The study was set in the Metropolitan Borough of Stockport and
      documented, from routine health services hospital admissions data, winter and
      summer differences in ACORN-specific, age- and sex-standardized hospital
      admission rates and ratios, for ischaemic heart disease, directly and indirectly
      standardized using the Stockport population as the standard. RESULTS: The
      expected social class gradient in ischaemic heart disease admissions was more
      clearly observable in the summer than in the winter. Affluent groups showed
      winter excess morbidity, less affluent groups showed summer excess morbidity.
      CONCLUSION: The data serendipitously indicate an alternative hypothesis - that
      winter excess morbidity is a feature of health benefits derived in the summer and
      differentially available to the more affluent, such as opportunities for outdoor
      leisure. This hypothesis deserves testing in a study designed for that purpose,
      although it is not entirely satisfactory as an explanation of existing data.

PMID- 11585199
TI  - Trends in deaths from drug overdose and poisoning in England and Wales 1993-1998.
AB  - BACKGROUND: The study examines time trends and sociodemographic aspects of drug
      poisoning deaths in England and Wales. METHODS: Socio-demographic data from the
      four drug groups most commonly used in poisoning were extracted, and annual age-
      and sex-specific mortality rates calculated. Enumeration districts were ranked
      into five groups on the basis of their Carstairs scores, and the number of deaths
      in each of the five groups was calculated. RESULTS: There were 15720 deaths from
      drug poisoning between 1993 and 1998. More deaths occurred in men than in women
      (10 223 versus 5497). Opiates were the most commonly used drugs in deaths from
      drug poisoning (32 per cent of deaths); mortality rates increased twofold for
      these drugs. Males had higher number of deaths from opiate poisoning than females
      (4523 versus 1221). Highest mortality rates from opiate poisoning (77.4 per
      million) occurred in men aged 24-35 years. Deaths from drug poisoning were
      strongly associated with deprivation. CONCLUSION: There are substantial socio
      demographic differences in mortality rates from drug poisoning.

PMID- 11585200
TI  - Quarterly communicable disease review January to March 2001.  From the PHLS
      Communicable Diseases Surveillance Centre.

PMID- 11585201
TI  - Births, gestation and birthweights in South Tees 1990-1996.

PMID- 11585202
TI  - Treatment of acute myocardial infarction.

PMID- 11585203
TI  - The biomedical imaging resource at Mayo Clinic.

PMID- 11585204
TI  - Fast kappa-space sample selection in MRSI with a limited region of support.
AB  - One of the primary drawbacks in the application of magnetic resonance
      spectroscopic imaging is the long acquisition times required to obtained the
      desired resolution. When region of support information is available, the number
      of phase-encoding steps and thus time can be reduced without loss of information
      if the kappa-space locations are chosen well. We propose to select locations
      using a rectangular sampling array that is shifted to various positions in kappa
      space to obtain the necessary sampling density. This method allows multiple
      samples to be selected simultaneously and reduces the computation required to
      evaluate the selection criterion. We present an efficient forward selection
      algorithm for optimizing the shift pattern so that the image can be reconstructed
      as reliably as possible from a periodic nonuniform set of samples. The proposed
      algorithm has important practical potential in that it can finish the selection
      in less than half a minute for typical image sizes and can reconstruct the image
      with fewer samples than regular sampling. With appropriate imaging hardware, this
      new algorithm makes selective sampling possible in a real-time image acquisition
      setting.

PMID- 11585205
TI  - A constrained modulus reconstruction technique for breast cancer assessment.
AB  - A reconstruction technique for breast tissue elasticity modulus is described.
      This technique assumes that the geometry of normal and suspicious tissues is
      available from a contrast-enhanced magnetic resonance image. Furthermore, it is
      assumed that the modulus is constant throughout each tissue volume. The
      technique, which uses quasi-static strain data, is iterative where each iteration
      involves modulus updating followed by stress calculation. Breast mechanical
      stimulation is assumed to be done by two compressional rigid plates. As a result,
      stress is calculated using the finite element method based on the well-controlled
      boundary conditions of the compression plates. Using the calculated stress and
      the measured strain, modulus updating is done element-by-element based on Hooke's
      law. Breast tissue modulus reconstruction using simulated data and phantom
      modulus reconstruction using experimental data indicate that the technique is
      robust.

PMID- 11585206
TI  - Ideal observer approximation using Bayesian classification neural networks.
AB  - It is well understood that the optimal classification decision variable is the
      likelihood ratio or any monotonic transformation of the likelihood ratio. An
      automated classifier which maps from an input space to one of the likelihood
      ratio family of decision variables is an optimal classifier or "ideal observer."
      Artificial neural networks (ANNs) are frequently used as classifiers for many
      problems. In the limit of large training sample sizes, an ANN approximates a
      mapping function which is a monotonic transformation of the likelihood ratio,
      i.e., it estimates an ideal observer decision variable. A principal disadvantage
      of conventional ANNs is the potential over-parameterization of the mapping
      function which results in a poor approximation of an optimal mapping function for
      smaller training samples. Recently, Bayesian methods have been applied to ANNs in
      order to regularize training to improve the robustness of the classifier. The
      goal of training a Bayesian ANN with finite sample sizes is, as with unlimited
      data, to approximate the ideal observer. We have evaluated the accuracy of
      Bayesian ANN models of ideal observer decision variables as a function of the
      number of hidden units used, the signal-to-noise ratio of the data and the number
      of features or dimensionality of the data. We show that when enough training data
      are present, excess hidden units do not substantially degrade the accuracy of
      Bayesian ANNs. However, the minimum number of hidden units required to best model
      the optimal mapping function varies with the complexity of the data.

PMID- 11585207
TI  - Retinal thickness measurements from optical coherence tomography using a Markov
      boundary model.
AB  - We present a system for detecting retinal boundaries in optical coherence
      tomography (OCT) B-scans. OCT is a relatively new imaging modality giving cross
      sectional images that are qualitatively similar to ultrasound. However, the axial
      resolution with OCT is much higher, on the order of 10 microm. Objective,
      quantitative measures of retinal thickness may be made from OCT images. Knowledge
      of retinal thickness is important in the evaluation and treatment of many ocular
      diseases. The boundary-detection system presented here uses a one-dimensional
      edge-detection kernel to yield edge primitives. These edge primitives are rated,
      selected, and organized to form a coherent boundary structure by use of a Markov
      model of retinal boundaries as detected by OCT. Qualitatively, the boundaries
      detected by the automated system generally agreed extremely well with the true
      retinal structure for the vast majority of OCT images. Only one of the 1450
      evaluation images caused the algorithm to fail. A quantitative evaluation of the
      retinal boundaries was performed as well, using the clinical application of
      automatic retinal thickness determination. Retinal thickness measurements derived
      from the algorithm's results were compared with thickness measurements from
      manually corrected boundaries for 1450 test images. The algorithm's thickness
      measurements over a 1-mm region near the fovea differed from the corrected
      thickness measurements by less than 10 microm for 74% of the images and by less
      than 25 microm (10% of normal retinal thickness) for 98.4% of the images. These
      errors are near the machine's resolution limit and still well below clinical
      significance. Current, standard clinical practice involves a qualitative, visual
      assessment of retinal thickness. A robust, quantitatively accurate system such as
      ours can be expected to improve patient care.

PMID- 11585208
TI  - The distribution of target registration error in rigid-body point-based
      registration.
AB  - Guidance systems designed for neurosurgery, hip surgery, spine surgery and for
      approaches to other anatomy that is relatively rigid can use rigid-body
      transformations to accomplish image registration. These systems often rely on
      point-based registration to determine the transformation and many such systems
      use attached fiducial markers to establish accurate fiducial points for the
      registration, the points being established by some fiducial localization process.
      Accuracy is important to these systems, as is knowledge of the level of that
      accuracy. An advantage of marker-based systems, particularly those in which the
      markers are bone-implanted, is that registration error depends only on the
      fiducial localization and is, thus, to a large extent independent of the
      particular object being registered. Thus, it should be possible to predict the
      clinical accuracy of marker-based systems on the basis of experimental
      measurements made with phantoms or previous patients. For most registration
      tasks, the most important error measure is target registration error (TRE), which
      is the distance after registration between corresponding points not used in
      calculating the registration transform. In this paper, we derive an approximation
      to the distribution of TRE; this is an extension of previous work that gave the
      expected squared value of TRE. We show the distribution of the squared magnitude
      of TRE and that of the component of TRE in an arbitrary direction. Using
      numerical simulations, we show that our theoretical results are a close match to
      the simulated ones.

PMID- 11585209
TI  - Evaluation of center-line extraction algorithms in quantitative coronary
      angiography.
AB  - Objective testing of centerline extraction accuracy in quantitative coronary
      angiography (QCA) algorithms is a very difficult task. Standard tools for this
      task are not yet available. We present a simulation tool that generates synthetic
      angiographic images of a single coronary artery with predetermined centerline and
      diameter function. This simulation tool was used creating a library of images for
      the objective comparison and evaluation of QCA algorithms. This technique also
      provides the means for understanding the relationship between the algorithms'
      performance and limitations and the vessel's geometrical parameters. In this
      paper, two algorithms are evaluated and the results are presented.

PMID- 11585210
TI  - ERS transform for the automated detection of bronchial abnormalities on CT of the
      lungs.
AB  - The identification of bronchi on Computed Tomography (CT) images of the lungs
      provides valuable clinical information in patients with suspected airways
      diseases including bronchiectasis, emphysema, or constrictive obliterative
      bronchiolitis. The automated recognition of the airways is, therefore, an
      important part of a diagnosis aid system for resolving potential ambiguities
      associated with intensity-based feature extractors. On CT images, near
      perpendicular cross sections of bronchi normally appear as elliptical rings and
      this paper presents a novel technique for their recognition. The proposed method,
      the edge-radius-symmetry (ERS) transform, is based on the analysis of the
      distribution of edges in local polar coordinates. Pixels are ranked according to
      local edge (E) strength, radial (R), uniformity and local symmetry (S). A
      discrete implementation of the technique is provided which reduces the
      computational cost of the ERS transform by using a geometric approximation of the
      intensity patterns. The identification of the adjacent pulmonary vessels with
      template matching then allows for the automated measurement of bronchial
      dilatation and bronchial wall thickening. Computationally, the method compares
      favorably with other methods such as the Hough transform. Noise-sensitivity of
      the technique was evaluated on a set of synthetic images and nine patients under
      investigation for suspected airways disease. Agreement for the automated scoring
      of the presence and severity of bronchial abnormalities was demonstrated to be
      comparable to that of an experienced radiologist (kappa statistics kappa > 0.5 ).

PMID- 11585211
TI  - Analysis of asymmetry in mammograms via directional filtering with Gabor
      wavelets.
AB  - This paper presents a procedure for the analysis of left-right (bilateral)
      asymmetry in mammograms. The procedure is based upon the detection of linear
      directional components by using a multiresolution representation based upon Gabor
      wavelets. A particular wavelet scheme with two-dimensional Gabor filters as
      elementary functions with varying tuning frequency and orientation, specifically
      designed in order to reduce the redundancy in the wavelet-based representation,
      is applied to the given image. The filter responses for different scales and
      orientation are analyzed by using the Karhunen-Loeve (KL) transform and Otsu's
      method of thresholding. The KL transform is applied to select the principal
      components of the filter responses, preserving only the most relevant directional
      elements appearing at all scales. The selected principal components, thresholded
      by using Otsu's method, are used to obtain the magnitude and phase of the
      directional components of the image. Rose diagrams computed from the phase images
      and statistical measures computed thereof are used for quantitative and
      qualitative analysis of the oriented patterns. A total of 80 images from 20
      normal cases, 14 asymmetric cases, and six architectural distortion cases from
      the Mini-MIAS (Mammographic Image Analysis Society, London, U.K.) database were
      used to evaluate the scheme using the leave-one-out methodology. Average
      classification accuracy rates of up to 74.4% were achieved.

PMID- 11585212
TI  - Extraction of motion strength and motor activity signals from video recordings of
      neonatal seizures.
AB  - This paper presents two methods developed to extract quantitative information
      from video recordings of neonatal seizures in the form of temporal motion
      strength and motor activity signals. Motion strength signals are extracted by
      measuring the area of the body parts that move during the seizure and the
      relative speed of motion using a combination of spatiotemporal subband
      decomposition of video, nonlinear filtering, and segmentation. Motor activity
      signals are extracted by tracking selected anatomical sites during the seizure
      using a modified version of a feature-tracking procedure developed for video,
      known as the Kanade-Lucas-Tomasi (KLT) algorithm. The experiments indicate that
      the temporal signals produced by the proposed methods provide the basis for
      differentiating myoclonic from focal clonic seizures and distinguishing these
      types of neonatal seizures from normal infant behaviors.

PMID- 11585214
TI  - Modern linac stereotactic radiosurgery systems have rendered the Gamma Knife
      obsolete.

PMID- 11585215
TI  - A formalism for independent checking of Gamma Knife dose calculations.
AB  - For stereotactic radiosurgery using the Leksell Gamma Knife system, it is
      important to perform a pre-treatment verification of the maximum dose calculated
      with the Leksell GammaPlan (DLGP) stereotactic radiosurgery system. This
      verification can be incorporated as part of a routine quality assurance (QA)
      procedure to minimize the chance of a hazardous overdose. To implement this
      procedure, a formalism has been developed to calculate the dose DCAL(X,Y,Z,dav,t)
      using the following parameters: average target depth (dav), coordinates (X,Y,Z)
      of the maximum dose location or any other dose point(s) to be verified, 3
      dimensional (3-dim) beam profiles or off-centerratios (OCR) of the four helmets,
      helmet size i, output factor Oi, plug factor Pi, each shot j coordinates
      (x,y,z)i,j, and shot treatment time (ti,j). The average depth of the target dav
      was obtained either from MRI/CT images or ruler measurements of the Gamma Knife
      Bubble Head Frame. DCAL and DLGP were then compared to evaluate the accuracy of
      this independent calculation. The proposed calculation for an independent check
      of DLGP has been demonstrated to be accurate and reliable, and thus serves as a
      QA tool for Gamma Knife stereotactic radiosurgery.

PMID- 11585216
TI  - Fluoroscopic study of tumor motion due to breathing: facilitating precise
      radiation therapy for lung cancer patients.
AB  - Target motion due to breathing is one of the major obstacles in dose escalation
      of radiation therapy to some tumors in the thoracoabdominal region. The
      development of beam gating or target motion tracking techniques provides a
      possibility to reduce normal tissue volume in a treatment field. Tumor motion
      monitoring in those techniques plays a crucial role, but has not yet been
      adequately explored. This paper reports our preliminary investigation on breath
      introduced tumor motion. Tumor locations and motion properties were determined
      from digitized fluoroscopic videos acquired during patient simulation. Image
      distortion due to irregularities in the imaging chain, such as the pincushion
      distortion, was corrected with a polynomial unwarping method. Temporal Fourier
      transformation of the fluoroscopic video was introduced to convert the motion
      information over time to a static view of a motion field, in which regions with
      different motion ranges can be directly measured. Patient breathing patterns vary
      from patient to patient and so does the kinematic behavior of individual tumors.
      In order to evaluate the feasibility for tracking internal target motion with
      nonionizing-radiation techniques, motion patterns between internal targets and
      external radio opaque markers placed on patient's chest during fluoroscopic video
      acquisition were compared. For some patients, significant motion phase
      discrepancies between an internal target and an external marker have been
      observed. Quantitative measurements are reported. These results will be useful in
      the design of a motion tracking or gated radiotherapy system.

PMID- 11585217
TI  - Theoretical estimation of absorbed dose to organs in radioimmunotherapy using
      radionuclides with multiple unstable daughters.
AB  - The toxicity and clinical utility of long-lived alpha emitters such as Ac-225 and
      Ra-223 will depend upon the fate of alpha-particle emitting unstable
      intermediates generated after decay of the conjugated parent. For example, decay
      of Ac-225 to a stable element yields four alpha particles and seven
      radionuclides. Each of these progeny has its own free-state biodistribution and
      characteristic half-life. Therefore, their inclusion for a more accurate
      prediction of absorbed dose and potential toxicity requires a formalism that
      takes these factors into consideration as well. To facilitate the incorporation
      of such intermediates into the dose calculation, a previously developed
      methodology (model 1) has been extended. Two new models (models 2 and 3) for
      allocation of daughter products are introduced and are compared with the
      previously developed model. Model 1 restricts the transport to a function that
      yields either the place of origin or the place(s) of biodistribution depending on
      the half-life of the parent radionuclide. Model 2 includes the transient time
      within the bloodstream and model 3 incorporates additional binding at or within
      the tumor. This means that model 2 also allows for radionuclide decay and further
      daughter production while moving from one location to the next and that model 3
      relaxes the constraint that the residence time within the tumor is solely based
      on the half-life of the parent. The models are used to estimate normal organ
      absorbed doses for the following parent radionuclides: Ac-225, Pb-212, At-211, Ra
      223, and Bi-213. Model simulations are for a 0.1 g rapidly accessible tumor and a
      10 g solid tumor. Additionally, the effects of varying radiolabled carrier
      molecule purity and amount of carrier molecules, as well as tumor cell antigen
      saturation are examined. The results indicate that there is a distinct advantage
      in using parent radionuclides such as Ac-225 or Ra-223, each having a half-life
      of more than 10 days and yielding four alpha particles per parent decay, in that
      lower doses to normal organs result for a given tumor dose in comparison to those
      radionuclides yielding fewer alpha particles. In model 2, which accounts for
      transit time through the blood, a dose of 20 Gy to a rapidly accessible 0.1 g
      tumor will result in a liver and kidney dose of 1.7 and 0.9 Gy, respectively from
      Ac-225. An equivalent dose to tumor from Ra-223 would yield a maximum normal
      organ dose of 0.4 and 0.3 Gy to bone and small intestines, respectively; the
      corresponding absorbed dose to small intestines from Pb-212 and Bi-213 is 2.2 and
      3.0 Gy, respectively.

PMID- 11585218
TI  - Beta versus gamma dosimetry close to Ir-192 brachytherapy sources.
AB  - The relative importance of the dose rate component owing to the beta spectrum
      emitted by 192Ir brachytherapy sources at the short radial distances of interest
      in intravascular and endobronchial applications is investigated. Separate
      dosimetric calculations, using Monte Carlo simulations, were performed for the
      gamma and beta dose rate components of an 192Ir ideal point source as well as
      real 192Ir source designs used in clinical practice including wire and seed
      sources and both Nucletron and Varian, old and new, high dose rate (HDR) source
      designs. A significant dose rate enhancement due to the beta spectrum emitted by
      192Ir, greater than 50% for radial distances r<2 mm, was observed for an ideal
      point source. For real source designs, however, the magnitude of this enhancement
      was found to depend strongly on the sources' geometric as well as compositional
      details of the active core and encapsulation. A detectable effect was found for
      the majority of the investigated sources at radial distances less than 1 mm, but
      overall findings suggest that the contribution of beta particles is not
      significant in 192Ir clinical intravascular applications that are currently
      carried out. However, since treatment of vessels with smaller diameters, in the
      future, may lead to the development of 192Ir sources and catheters of reduced
      diameters, the potential effect of the beta spectrum in terms of dose enhancement
      to tissues in close proximity to 192Ir sources should not be ignored.

PMID- 11585219
TI  - Self-absorption correction for 32P, 198Au and 188Re stents: dose point kernel
      calculations versus Monte Carlo.
AB  - Monte Carlo simulations of dose distributions around radioactive stents are very
      time intensive. Thus, in order to calculate the dose distribution around a 188Re
      stent, we chose to test a point kernel method, a method which is known to be
      faster but the accuracy of which has not been established for this application.
      The dose point kernel method, which takes into account absorption in the strut
      material (=self-absorption), was based on different beta-emitting point source
      distributions in water by itself and surrounded by steel spheres of different
      thicknesses. This information was input into an integration routine that modeled
      either a Palmaz-Schatz or Multilink stent. The dose distributions around 198Au
      and 32P stents calculated with the dose point kernel method were compared to
      those calculated using EGS4 and MCNP 4B Monte Carlo methods. The resulting
      correction for self-absorption in steel was distance dependent and averaged 1.12
      for 32P and 1.25 for 198Au stents. The dose point kernel method gave nearly
      identical results to these full Monte Carlo simulations and was thus used to
      calculate the dose distributions around a 188Re stent. Although 188Re has a half
      life of only 17 hours, it is posited to be useful for radioactive restenosis
      prevention, given that a recently developed rapid electrodeposition procedure
      allows stents to be made radioactive, at predetermined activities, within 15
      minutes. The dose point kernel calculations of a 188Re-coated Multilink stent
      were compared to its radiochromic film measurements. The dose fall-off agreed
      with the calculations within 5% over 0.4 to 3.5 mm from the stent surface. The
      dose point kernel method is a valuable tool to determine depth dose distributions
      around activated stents taking into account the detailed geometry and the self
      absorption in the struts. It not only requires much less processing time than
      Monte Carlo methods, but also allows the use of higher resolutions in modeling
      the geometry, which leads to more accurate self-absorption correction factors.

PMID- 11585220
TI  - An investigation on the use of removal-diffusion theory for BNCT treatment
      planning: a method for determining proper removal-diffusion parameters.
AB  - This paper outlines a method for determining proper removal-diffusion parameters
      to be used in removal-diffusion theory calculations for the purpose of BNCT
      treatment planning. Additionally, this paper demonstrates that, given the proper
      choice of removal-diffusion parameters, removal-diffusion theory may provide an
      accurate calculation technique for determining absorbed dose distributions for
      the purpose of BNCT treatment planning. For a four-group, one-dimensional
      calculation in water, this method was used to determine values for the neutron
      scattering cross sections, neutron removal cross sections, neutron diffusion
      coefficients, and extrapolation distances. These values were then used in a one
      dimensional DIF3D calculation. The results of the DIF3D calculation showed a
      maximum deviation of 2.5% from a MCNP calculation performed for the same
      geometry.

PMID- 11585221
TI  - Application of the new MultiTrans SP3 radiation transport code in BNCT dose
      planning.
AB  - Dose planning in boron neutron capture therapy (BNCT) is a complex problem and
      requires sophisticated numerical methods. In the framework of the Finnish BNCT
      project, new deterministic three-dimensional radiation transport code MultiTrans
      SP3 has been developed at VTT Chemical Technology, based on a novel application
      of the tree multigrid technique. To test the applicability of this new code in a
      realistic BNCT dose planning problem, cylindrical PMMA (polymethyl-methacrylate)
      phantom was chosen as a benchmark case. It is a convenient benchmark, as it has
      been modeled by several different codes, including well-known DORT and MCNP.
      Extensive measured data also exist. In this paper, a comparison of the new
      MultiTrans SP3 code with other methods is presented for the PMMA phantom case.
      Results show that the total neutron dose rate to ICRU adult brain calculated by
      the MultiTrans SP3 code differs less than 4% in 2 cm depth in phantom (in thermal
      maximum) from the DORT calculation. Results also show that the calculated
      197Au(n,gamma) and 55Mn(n,gamma) reaction rates in 2 cm depth in phantom differ
      less than 4% and 1% from the measured values, respectively. However, the photon
      dose calculated by the MultiTrans SP3 code seems to be incorrect in this PMMA
      phantom case, which requires further studying. As expected, the deterministic
      MultiTrans SP3 code is over an order of magnitude faster than stochastic Monte
      Carlo codes (with similar resolution), thus providing a very efficient tool for
      BNCT dose planning.

PMID- 11585223
TI  - A method for calculating the dose to a multi-storey building due to radiation
      scattered from the roof of an adjacent radiotherapy facility.
AB  - With modern urbanization trends, situations occur where a general-purpose multi
      storey building would have to be constructed adjacent to a radiotherapy facility.
      In cases where the building would not be in the primary x-ray beam, "skyshine"
      radiation is normally accounted for. The radiation scattered from the roof side
      wise towards the building can also be a major contributing factor. However,
      neither the NCRP reports nor recently published literature considered this. The
      current paper presents a simple formula to calculate the dose contribution from
      scattered radiation in such circumstances. This equation includes workload, roof
      thickness, field size, distance to the reference point and a normalized angular
      photon distribution function f(theta), where theta is the angle between central
      axis of the primary beam and photon direction. The latter was calculated by the
      Monte Carlo method (EGS4 code) for each treatment machine in our department. For
      angles theta exceeding approximately 20 degrees (i.e., outside the primary beam
      and its penumbra) the angular distribution function f(theta) was found to have
      little dependence on the shielding barrier thickness and the beam energy. An
      analytical approximation of this function has been obtained. Measurements have
      been performed to verify this calculation technique. An agreement within 40% was
      found between calculated and measured dose rates. The latter combined the
      scattered radiation and the dose from "skyshine" radiation. Some overestimation
      of the dose resulted from uncertainties in the radiotherapy building drawings and
      in evaluation of the "skyshine" contribution.

PMID- 11585222
TI  - Miniature tissue-equivalent proportional counters for BNCT and BNCEFNT dosimetry.
AB  - A dual miniature tissue-equivalent proportional counter (TEPC) system has been
      developed to facilitate microdosimetry for Boron Neutron Capture Therapy (BNCT).
      This system has been designed specifically to allow the analysis of the single
      event charged particle spectrum in phantom in high intensity BNCT beams and to
      provide this microdosimetric information with excellent spatial resolution.
      Paired A-150 and 10B-loaded A-150 TEPCs with 12.3 mm3 collecting volumes have
      been constructed. These TEPCs allow more accurate neutron dosimetry than current
      techniques, offer a direct measure of the boron neutron capture dose, and provide
      a framework for predicting the biological effectiveness of the absorbed dose.
      Design aspects and characterization of these detectors are reviewed, along with
      an exposition of the advantages of microdosimetry using these detectors over
      conventional dosimetry methods. In addition, the utility of this technique for
      boron neutron capture enhancement of fast neutron therapy (BNCEFNT) is discussed.

PMID- 11585224
TI  - Producing parallel x rays with a bent-crystal monochromator and an x-ray tube.
AB  - A bent Laue monochromator and a conventional x-ray tube were used to produce a
      fan beam that was parallel in the plane perpendicular to the plane of the fan.
      The x-ray fan beam was tunable in energy and had about 12% energy bandwidth at a
      slice height of 5 mm when tuned to 50 keV. The beam's energy was slightly coupled
      to the vertical position on the beam's height. The slice height could be varied
      from 1 to 10 mm. The flux at 50 keV was approximately 2x10(6) photons/mm2/s with
      a rotating anode tungsten x-ray tube operating at 120 kVp and 100 mA. The narrow
      energy bandwidth of the beam produced is advantageous over a conventional
      divergent polychromatic beam for all radiography applications, while the
      parallelism of the beam enhances its intensity by about threefold and offers some
      advantages for computed tomography.

PMID- 11585225
TI  - Selection of an optimal neural network architecture for computer-aided detection
      of microcalcifications--comparison of automated optimization techniques.
AB  - Many computer-aided diagnosis (CAD) systems use neural networks (NNs) for either
      detection or classification of abnormalities. Currently, most NNs are "optimized"
      by manual search in a very limited parameter space. In this work, we evaluated
      the use of automated optimization methods for selecting an optimal convolution
      neural network (CNN) architecture. Three automated methods, the steepest descent
      (SD), the simulated annealing (SA), and the genetic algorithm (GA), were
      compared. We used as an example the CNN that classifies true and false
      microcalcifications detected on digitized mammograms by a prescreening algorithm.
      Four parameters of the CNN architecture were considered for optimization, the
      numbers of node groups and the filter kernel sizes in the first and second hidden
      layers, resulting in a search space of 432 possible architectures. The area Az
      under the receiver operating characteristic (ROC) curve was used to design a cost
      function. The SA experiments were conducted with four different annealing
      schedules. Three different parent selection methods were compared for the GA
      experiments. An available data set was split into two groups with approximately
      equal number of samples. By using the two groups alternately for training and
      testing, two different cost surfaces were evaluated. For the first cost surface,
      the SD method was trapped in a local minimum 91% (392/432) of the time. The SA
      using the Boltzman schedule selected the best architecture after evaluating, on
      average, 167 architectures. The GA achieved its best performance with linearly
      scaled roulette-wheel parent selection; however, it evaluated 391 different
      architectures, on average, to find the best one. The second cost surface
      contained no local minimum. For this surface, a simple SD algorithm could quickly
      find the global minimum, but the SA with the very fast reannealing schedule was
      still the most efficient. The same SA scheme, however, was trapped in a local
      minimum on the first cost surface. Our CNN study demonstrated that, if
      optimization is to be performed on a cost surface whose characteristics are not
      known a priori, it is advisable that a moderately fast algorithm such as a SA
      using a Boltzman cooling schedule be used to conduct an efficient and thorough
      search, which may offer a better chance of reaching the global minimum.

PMID- 11585226
TI  - Dependence of computer classification of clustered microcalcifications on the
      correct detection of microcalcifications.
AB  - Our purpose was to study the dependence of computer performance in classifying
      clustered microcalcifications as malignant or benign on the correct detection of
      microcalcifications. Specifically, we studied the effects of computer-detected
      true-positive microcalcifications and computer-detected false-positive
      microcalcifications in true microcalcification clusters. Using a database of 100
      mammograms, we compared computer classification performance obtained from
      computer-detected microcalcifications to (1) computer classification performance
      obtained from manually identified microcalcifications, and (2) radiologists'
      performance. When an artificial neural network (ANN) was trained with manually
      identified microcalcifications, computer classification performance was
      comparable to or better than radiologists' performance as the number of computer
      detected true-positive microcalcifications decreased to 40% and as the number of
      computer-detected false-positive microcalcifications increased to 50%. Further
      loss in computer-detected true-positive microcalcifications degraded
      classification performance substantially. Moreover, training the ANN with
      computer-detected microcalcifications also degraded computer classification
      performance. These results show that computer performance in classifying
      clustered microcalcifications as malignant or benign is insensitive to moderate
      decreases in computer-detected true-positive microcalcifications and moderate
      increases in computer-detected false-positive microcalcifications.

PMID- 11585227
TI  - Microwave-induced thermoacoustic tomography using multi-sector scanning.
AB  - A study of microwave-induced thermoacoustic tomography of inhomogeneous tissues
      using multi-sector scanning is presented. A short-pulsed microwave beam is used
      to irradiate the tissue samples. The microwave absorption excites time-resolved
      acoustic waves by thermoelastic expansion. The amplitudes of the acoustic waves
      are strongly related to locally absorbed microwave-energy density. The acoustic
      waves may propagate in all spatial directions. A focused ultrasonic transducer is
      employed to acquire temporal acoustic signals from multiple directions. Each
      detected signal is converted into a one-dimensional (1D) image along the acoustic
      axis of the transducer. The cross-sectional images of the tissue samples are
      calculated by combining all of the 1D images acquired in the same planes.

PMID- 11585228
TI  - Variation in interpretation of the AAPM TG-43 geometry factor leads to
      unclearness in brachytherapy dosimetry.

PMID- 11585229
TI  - Spinal cord medicine: physician scientists can make a difference.

PMID- 11585230
TI  - "Look to your right, look to your left...".

PMID- 11585231
TI  - Pharmacological treatment of acute spinal cord injury: how do we build on past
      success?
AB  - Most acute spinal cord injuries (SCI) do not involve complete transection of the
      spinal cord; typically, a rim of white matter survives. The potential for
      neurological recovery depends on optimal preservation of the ascending and
      descending white matter axons and their normal myelination. Pharmacologic
      strategies focus on the control of secondary injury processes, primarily lipid
      peroxidation (LP), and the salvage of as much white matter as possible. The first
      effective neuroprotective agent was methylprednisolone (MP), a
      glucocorticosteroid that in high doses improves neurological recovery in animals
      and humans following acute SCI. Tirilazad is a more targeted non-glucocorticoid
      LP inhibitor that has been shown to be neuroprotective and has fewer side effects
      than MP. Future SCI therapy is likely to encompass various neuroprotective
      agents, including inhibitors of LP, inhibitors of the nitric oxide-derived
      reactive oxygen species peroxynitrite, inhibitors of calpain (which is
      responsible for degrading the spinal cord cytoskeleton), and inhibitors of post
      traumatic apoptosis of neurons and myelin-forming oligodendroglia. In addition,
      neuroprotective strategies will eventually be followed by neurorestorative agents
      that stimulate the plasticity of surviving neural pathways, and will be used in
      conjunction with other neurorestorative therapies like cell transplantation and
      gene therapy techniques.

PMID- 11585232
TI  - Restoring sexual function by electrical activation of the nervous system: a
      symposium.

PMID- 11585233
TI  - Neural circuitry involved in sexual function.
AB  - BACKGROUND: Neurological injury results in devastating sexual deficits in both
      men and women. Effective treatment requires an understanding of the central
      nervous system (CNS) pathways and physiology. This article emphasizes the
      essential similarities in the pathways and physiology of sexual function in men
      and women. METHODS: Literature review. FINDINGS: Systems within the spinal cord
      are fully capable of generating a large number of sexual responses. Spinal sexual
      centers may be activated by genital afferents or by descending commands from
      higher CNS sites. Normal functioning probably involves activation of spinal
      centers by both descending pathways and afferent stimulation. Afferent
      stimulation also modulates the activity of supraspinal sites, creating a positive
      feedback system. Descending control consists of powerful inhibitory and
      excitatory pathways. An important serotonergic inhibitory pathway has been
      demonstrated. The medial preoptic region participates in the integration of
      hormonal and sensory cues necessary for sexual behavior. The medial amygdala and
      paraventricular nucleus of the hypothalamus also play essential excitatory roles.
      The paraventricular nucleus projects directly to relevant spinal sites,
      indicating another important pathway for excitatory control. CONCLUSIONS: Recent
      advances have markedly enhanced our understanding of the physiology,
      pharmacology, molecular biology and pathology of sexual mechanisms. This
      knowledge base is essential in order to understand changes in sexual mechanisms
      that follow spinal cord injury, and for the development of effective
      interventions to maximize sexual function in men and women with spinal cord
      injury.

PMID- 11585234
TI  - Sexual response in women with spinal cord injury: neurologic pathways and
      recommendations for the use of electrical stimulation.
AB  - BACKGROUND: Determination of the exact level and degree of a woman's spinal cord
      injury (SCI) has allowed researchers to document the aspects of sexual response
      that are altered with specific patterns of SCI. Based on these findings,
      recommendations can be made regarding the development and testing of electrical
      stimulation systems designed to facilitate sexual responses in women with SCI.
      DESIGN: Literature review. FINDINGS: Studies of the arousal stages of response
      indicate that psychogenic vaginal lubrication is maintained with pinprick
      sensation in T11-T12 dermatomes, and that reflex lubrication occurs in women with
      upper motor neuron injuries affecting the sacral segments. Studies of the
      orgasmic stage support the hypothesis that orgasm is a reflex response of the
      autonomic nervous system that appears to depend on an intact sacral arc.
      CONCLUSIONS: Laboratory studies of arousal and orgasm among women with different
      types of SCI, and comparisons with able-bodied controls, provide valuable
      information regarding female sexual neurophysiology. Electrical stimulation can
      be used to improve sexual response, as well as bladder and bowel function.
      Interventions that interfere with the sacral reflex arc, such as sacral
      rhizotomy, can impair the ability to achieve orgasm. To develop alternative
      treatment protocols, further investigation of sexual response and orgasm is
      recommended.

PMID- 11585235
TI  - The "uninhibited rectum": a cause of fecal incontinence.
AB  - OBJECTIVE: The uninhibited (unstable) rectum has been defined as a cause offecal
      incontinence (FI) in patients with supraconal lesions. In this study, we tested
      the hypothesis that the uninhibited rectum may be a cause of FI in patients with
      normal anal pressure and sphincteric mechanism who were considered to have
      idiopathic FI. METHODS: The study comprised 82 patients (mean age 38.2 +/- 11.2
      years; 58 women and 24 men) with idiopathic FI and a control group of 20 healthy
      volunteers (mean age 36.3 +/- 10.6 years; 14 women and 6 men). Inclusion criteria
      for FI patients were normal electromyogram of the external anal sphincter and
      puborectalis muscle, and normal anal sensation, pressure, and endosonography.
      Rectometry was performed using rectal balloon inflation with CO2 at a rate of 150
      cc/min. Rectometrograms were assessed quantitatively and qualitatively. RESULTS:
      In 79 FI patients, the first rectal sensation was not felt. Urge was perceived at
      the time of balloon expulsion, which could not be prevented by voluntary
      sphincteric squeeze. In the remaining 3 patients, the first sensation was
      perceived but urge coincided with balloon expulsion. Rectometrography showed
      moderate and gross fluctuations in the tone limb that were not associated with
      significant changes in intra-abdominal pressure. This contrasted with normal
      subjects in whom the tone limb exhibited no fluctuations or minor fluctuations
      that roughly paralleled the intra-abdominal pressure fluctuations. The rectal
      distension volume at balloon expulsion was significantly lower in FI patients
      than in controls (P < .05). CONCLUSIONS: These findings suggest that FI can be
      explained by the fact that the first rectal sensation was that of urge, which was
      perceived synchronously with balloon expulsion. That is, the balloon had been
      expelled before the patient could voluntarily squeeze the sphincters to abort
      expulsion. We postulated that during inflation with small volumes, the rectum did
      not adapt as in controls, but responded with contractions, which appear to be
      reflected in the multiple fluctuations in the tone limb. FI in these patients
      appears to be a consequence of the unstable or uninhibited rectum.

PMID- 11585237
TI  - Spinal cord injury: facts and figures at a glance.

PMID- 11585238
TI  - Hyperlipidemia and cardiovascular disease after organ transplantation.
AB  - Hyperlipidemia, a frequent and persistent complication after solid organ
      transplantation, contributes to cardiovascular morbidity and mortality and may
      influence the development of allograft vasculopathy. The pathogenesis of
      posttransplantation hyperlipidemia is not fully understood, although several
      epidemiological factors are strongly implicated including age, weight,
      pretransplantation lipid levels, and immunosuppressive therapy. Management
      strategies to reduce hyperlipidemia and modify cardiovascular risk include
      dietary restrictions and the use of lipid-lowering agents. The selective use of
      immunosuppressants, such as tacrolimus, that have neutral or fewer adverse
      effects on lipid metabolism may also provide a useful option. A combination of
      lipid-lowering therapies and optimization of immunosuppressive regimens
      compatible with prolonged allograft survival is probably necessary to
      significantly reduce posttransplantation hyperlipidemia and its potentially
      harmful consequences.

PMID- 11585239
TI  - Graft function and other risk factors as predictors of cardiovascular disease
      outcome.
AB  - The high incidence of cardiovascular disease after renal transplantation is
      related to a high prevalence and accumulation of risk factors before and after
      transplantation. Hypertension, posttransplantation diabetes, and hyperlipidemia
      are well-recognized risk factors for the development of cardiovascular events
      after renal transplantation and are strongly associated with immunosuppressive
      therapy. Hyperhomocysteinemia is a potential risk factor for cardiovascular
      disease in renal transplant recipients, but although a growing matter of study, a
      direct association with immunosuppressive agents is not yet proven. In addition
      to treatment intervention, risk management should also involve tailoring the
      immunosuppressive regimen to minimize the more indirect cardiovascular risk
      factors such as renal dysfunction and acute rejection.

PMID- 11585240
TI  - Strategies to minimize immunological and nonimmunological risk factors in the
      renal transplant population.
AB  - To improve long-term outcome after renal transplantation, attention should be
      placed on the tailored use of immunosuppressive regimens that have a more
      favorable impact on the immunological and nonimmunological risk profiles of an
      individual recipient. Tacrolimus is widely used for maintenance and rejection
      immunosuppression in solid organ transplantation, and compared with cyclosporine,
      its use in renal transplantation is associated with a reduced incidence and
      severity of acute rejection and a more positive effect on known cardiovascular
      risk factors. Recent experience with tacrolimus-based therapy has demonstrated an
      improved lipid profile and lower arterial blood pressure, with less requirement
      for lipid-lowering and antihypertensive medication compared with cyclosporine,
      without significantly increasing the risk of long-term insulin-dependent
      posttransplant diabetes mellitus. The advantageous effects of tacrolimus on both
      immunological and nonimmunological risk factors offer potential benefits for long
      term graft function and survival.

PMID- 11585241
TI  - Posttransplant cardiovascular risk: impact on long-term patient survival. 
      Introduction.

PMID- 11585242
TI  - Epidemiology of cardiovascular disease after renal transplantation.
AB  - A large proportion of late renal allograft failures are attributable to patient
      death with a functioning graft, with almost half of the deaths related to
      cardiovascular events. Using data from the Framingham Heart Study and our own
      renal transplant population, risk factors for cardiovascular disease in the
      general population, such as hypertension, hyperlipidemia, and cigarette smoking,
      were found to be predictive in renal transplant recipients. However, diabetes
      mellitus dramatically elevated the risk in renal transplantation. Also, two or
      more acute rejection episodes in the first year after transplantation were
      associated with a greater risk, whereas pretransplantation nephrectomy and higher
      serum albumin levels reduced the risk for ischemic heart events.
      Pretransplantation screening assists identification of patients who are at risk
      of, or who have preexisting, cardiovascular disease. Management interventions
      such as antihypertensives, lipid-lowering agents, antidiabetic therapy, aspirin
      prophylaxis, and smoking cessation have a positive impact on known risk factors
      for cardiovascular disease, and their use may decrease cardiovascular morbidity
      and mortality in renal transplant recipients.

PMID- 11585243
TI  - Mechanisms and consequences of arterial hypertension after renal transplantation.
AB  - The high incidence of hypertension after renal transplantation contributes to the
      risk of cardiovascular morbidity and mortality in renal transplant recipients.
      Although cyclosporine has been influential in the improvement of transplant
      outcome, it has emerged as a major cause of hypertension after organ
      transplantation. The underlying pathophysiological mechanisms of cyclosporine
      induced hypertension include enhanced sympathetic nervous system activity, renal
      vasoconstriction, and sodium/water retention. Hypertension is also significantly
      associated with reduced graft survival and thereby requires aggressive treatment
      intervention. Calcium channel blockers may offer some advantages over angiotensin
      converting enzyme inhibitors for the treatment of hypertension in stable renal
      transplant recipients. Nevertheless, selection of the most appropriate
      antihypertensive agent should take into account the possibility of
      pharmacokinetic interactions with immunosuppressive agents. There is evidence to
      suggest that the use of tacrolimus-based immunosuppression induces less
      hypertension compared with cyclosporine. Not only do patients receiving
      tacrolimus tend to require less antihypertensive therapy, but converting patients
      from cyclosporine to tacrolimus has been shown to result in significant
      reductions in blood pressure. Thus, tacrolimus may be associated with an improved
      cardiovascular risk profile in renal transplant recipients.

PMID- 11585244
TI  - Cell death signaling in the cerebellum in Creutzfeldt-Jakob disease.
AB  - Examination of the expression of proteins linked with signaling pathways
      commanding cell death and cell survival has been carried out to increase
      understanding on the mechanisms leading to cell death in the cerebellum in
      Creutzfeldt-Jakob disease (CJD). Expression of Fas, Fas ligand (Fas-L), ERK, MEK,
      Bcl-2, Bax, N-myc, c-myc, pro-caspase-2 and active caspase-3 was examined by
      immunohistochemistry in the cerebellum of six patients with sporadic CJD, three
      patients with olivopontocerebellar atrophy (OPCA) and six age-matched controls.
      No modifications in the expression of these proteins were observed in granule
      cells in CJD and OPCA when compared with controls, except in a few cells in the
      molecular and granular layers in CJD that displayed dense homogeneous active
      caspase-3 immunostaining. This suggests selective activation of caspase-3 in
      association with increased cellular vulnerability in CJD. No modifications in pro
      caspase-2 and c-myc immunoreactivity were observed in Purkinje cells in diseased
      brains when compared with controls. However, increased diffuse Fas, Fas-L, MEK,
      ERK and Bax expression, and enhanced granular active caspase-3 immunoreactivity
      was found in the cytoplasm of Purkinje cells in CJD. Increase in Bcl-2 and N-myc
      occurred in Purkinje cells in CJD and OPCA. These results indicate that enhanced
      Fas, Fas-L, MERK, ERK, Bax and granular active caspase-3 expression is not lethal
      to Purkinje cells in CJD, whereas increased Bcl-2 and N-myc does not preclude per
      se cell death or death survival in CJD and OPCA. These findings point to the
      likelihood that expression of these cell death proteins in neurodegeneration has
      functional roles differing from those related with apoptosis.

PMID- 11585246
TI  - Comparison of amyloid deposits and infiltration of enteric nervous system in the
      upper with those in the lower gastrointestinal tract in patients with familial
      amyloidotic polyneuropathy.
AB  - Gastrointestinal (GI) complications in familial amyloidotic polyneuropathy (FAP)
      are invariably present during the course of the disease. The aim of this study
      was to investigate amyloid deposits in the myenteric plexus of the stomach and
      small intestine in FAP patients and compare the results with those of the colon.
      Six FAP patients were included in the study. The myenteric plexus and the number
      of macrophages (CD68) and blood vessels were immunostained and quantified by
      computerised image analysis. Double staining for amyloid and nerve elements was
      used to detect amyloid infiltration in the myenteric plexus. Amyloid was found
      predominantly in the walls of blood vessels, and was detected in the nerves of
      five FAP patients and in 18% of the examined ganglia of the myenteric plexus of
      the stomach. In the small intestine, 6% of examined ganglia showed amyloid
      deposits. In contrast, no deposits were found in the myenteric plexus of the
      colon. CD68-positive cells showed no difference in three parts of the GI tract.
      Most amyloid deposits were noted in the stomach, followed by the small intestine.
      There are significantly more blood vessels in the stomach and small intestine
      compared with the colon, and the amount of amyloid correlated with the number of
      blood vessels, and not with the amount of nerves and ganglia. The enteric nerve
      system is not a targeted organ for amyloid deposition in FAP.

PMID- 11585245
TI  - Vascular endothelial growth factor-A and -C protein up-regulation and early
      angiogenesis in a rat photothrombotic ring stroke model with spontaneous
      reperfusion.
AB  - This study explored the temporal expression pattern of two subtypes of vascular
      endothelial growth factor (VEGF) proteins and three subforms of their receptors
      as well as endothelial proliferation in adult rats subjected to photothrombotic
      ring stroke with spontaneous reperfusion in the cortical region at risk. The
      exposed crania of halothane-anesthetized, temperature- and blood gas-controlled
      male Wistar rats were irradiated with a ring laser beam started simultaneously
      with systemic injection of the photosensitizer erythrosin B. Rats were repeatedly
      injected with 5-bromodeoxyuridine (BrdU) after stroke induction.
      Immunohistochemistry of coronal brain sections showed that VEGF protein subtype C
      increased simultaneously with subtype A in the ring lesion region at 2 h after
      irradiation. In the cortical region at risk (i.e., the penumbra-like zone),
      increased VEGF-C and VEGF-A immunostaining was seen at 24 h with sustained
      appearance up to 72 h after ischemic onset. Correspondingly, the VEGF-C-specific
      receptor flt-4 and the VEGF-A receptors flt-1 and flk-1 were up-regulated in a
      temporal sequence similar to that of their agonist proteins in the cortical ring
      lesion and the region at risk. At 48 h after stroke induction, proliferating BrdU
      immunopositive endothelial cells formed microvessels in the post-ischemic
      cortical region at risk. These vessels became more pronounced at 72 h and were
      still visible at 100 days after the stroke. This study suggests that VEGF-C and
      its receptor flt-4 may cooperate with VEGF-A and its receptors flt-1 and flk-1 to
      promote early angiogenesis after stroke, which may in turn contribute to
      spontaneous reperfusion in this focal thromboembolic stroke model.

PMID- 11585247
TI  - Copper chaperone for superoxide dismutase co-aggregates with superoxide dismutase
      1 (SOD1) in neuronal Lewy body-like hyaline inclusions: an immunohistochemical
      study on familial amyotrophic lateral sclerosis with SOD1 gene mutation.
AB  - The copper chaperone for superoxide dismutase (CCS) interacts with Cu/Zn-binding
      superoxide dismutase 1 (SOD1) specifically and delivers copper to SOD1. To
      determine the role of the CCS-SOD1 interaction in the pathogenesis of SOD1
      mutated familial amyotrophic lateral sclerosis (FALS) patients, we produced an
      affinity-purified rabbit antibody against CCS and investigated the
      immunohistochemical localization of both CCS and SOD1 in neuronal Lewy body-like
      hyaline inclusions (LBHIs) in the spinal cords of two FALS patients with a two
      base pair deletion at codon 126 in the SOD1 gene and three FALS patients with an
      Ala to Val substitution at codon 4. The LBHIs in anterior horn cells from the
      five FALS patients showed identical immunoreactivities for CCS: the reaction
      product deposits with the antibody against CCS were generally restricted to the
      periphery of the core and halo-type LBHIs. The localizations of the
      immunoreactivities for CCS and SOD1 were similar in the inclusions: both CCS and
      SOD1 colocalized in neuronal LBHIs in the five mutant SOD1-linked FALS patients.
      Our results suggest that the specific interaction and aggregation of CCS-SOD1
      (probably CCS-mutant SOD1) in SOD1-mutated FALS patients may amplify the
      formation of inclusions and emphasize a more marked mutant SOD1-mediated
      toxicity.

PMID- 11585248
TI  - Acute up-regulation of brain-derived neurotrophic factor expression resulting
      from experimentally induced injury in the rat spinal cord.
AB  - Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor
      family of trophic factors, has multiple functions including a role in the
      promotion of neuronal survival and nerve fiber elongation in both the central and
      the peripheral nervous systems. We assessed the expression of endogenous BDNF
      following an experimentally induced compression injury to the spinal cord.
      Expression of BDNF mRNA was increased following the spinal cord injury; reaching
      maximum levels 24 h after the injury. Expression of BDNF mRNA returned to the
      levels observed in sham-operated control animals within 3 days of the injury.
      Using the in situ hybridization technique, we observed a wide distribution of
      BDNF expression among the different cell types in the spinal cord, including
      motor and sensory neurons, and in glia cells, including astrocytes. We also
      observed expression of BDNF in putative macrophages and/or microglia; however,
      this effect was not observed until day 7 following spinal cord injury. These
      results suggest that BDNF is synthesized in both neurons and astrocytes during
      the acute response to injury to the spinal cord, functioning in a mainly
      neuroprotective role. This is followed by a later phase of expression in which
      BDNF is produced by macrophages and/or microglia, apparently functioning in a
      restorative capacity.

PMID- 11585249
TI  - Cognitive and histopathological outcome after weight-drop brain injury in the
      rat: influence of systemic administration of monoclonal antibodies to ICAM-1.
AB  - The aim of this study was to evaluate whether treatment with the anti-ICAM-1
      antibody 1A29 influences functional or histopathological outcome following severe
      controlled cortical contusion in rats. The spatial learning deficits were studied
      using Morris water maze (MWM) paradigm in which the animals were given four daily
      acquisition trials for four consecutive days, starting on day 10 post-injury.
      Both 1A29-treated (n=8) and vehicle-treated (n=8) traumatized animals needed
      longer time than sham-operated rats (n=8) to find the hidden escape platform on
      days 11, 12 and 13. Compared to shams, significantly increased escape latency was
      noted on day 12 in vehicle-treated group and on days 12 and 13 in 1A29-treated
      animals. MWM performance did not differ significantly between the two trauma
      groups. Histopathological evaluation of the injured brains 15 days after trauma
      revealed ipsilateral cortical cavitation as well as ipsilateral hippocampal and
      thalamic lesions. MAP2 immunostaining showed a nonsignificant tendency towards
      more pronounced hippocampal injury in the 1A29-treated animals. Image analysis of
      glial fibrillary acidic protein- and ionized calcium binding adapter molecule 1
      immunostained sections revealed astrocytic activation in the ipsilateral thalamus
      and microglial activation in both ipsilateral thalamus and hippocampus of
      traumatized animals, but no significant differences between the trauma groups. In
      summary, this study shows that spatial memory deficits occur following a weight
      drop injury to the rat brain. Treatment with the anti-ICAM-1 antibody 1A29 did
      not significantly change the recorded functional or histopathological measures of
      outcome.

PMID- 11585250
TI  - Expression of smooth muscle proteins in cavernous and arteriovenous
      malformations.
AB  - Cavernous malformations (CVMs) and arteriovenous malformations (AVMs) were
      immunostained for three smooth muscle cell (SMC)-specific protein markers (smooth
      muscle alpha-actin, SM1 and SM2). Smooth muscle alpha-actin, a widely used marker
      of SMCs, is reportedly one of the earliest proteins expressed during
      differentiation of SMCs and expressed in some kinds of mesoderm-derived cells. In
      contrast, SM1, an isoform of myosin heavy chain (MHC), is detected only in SMCs.
      SM2 is another MHC isoform and expressed in the contractile phenotype of SMC. All
      14 intraaxial CVMs were positive for smooth muscle alpha-actin, but SM1 was
      detected in only three of them and SM2 was not found. Their staining pattern
      resembled that of normal intraparenchymal and pial veins. All 15 cerebral AVMs
      and 5 out of 6 extraaxial CVMs from the cavernous sinus, orbit and scalp were
      positive for all three markers, as were the normal cerebral arteries. The venous
      components of AVMs, as well as the arterial components, expressed SM2, and were
      different from normal veins in the brain and intraaxial CVMs. This study shows
      that the histological analysis using the three markers for SMC is useful to
      differentiate intraaxial CVM from AVM and extraaxial CVMs.

PMID- 11585251
TI  - Histochemical and morphometrical analysis of skeletal muscle in spontaneous
      diabetic WBN/Kob rat.
AB  - Spontaneous diabetic WBN/Kob rats develop diabetic peripheral neuropathy
      characterized by primary segmental demyelination and secondary axonal
      degeneration. The objective of this study was to evaluate the histochemical and
      morphometric characteristics of the lesions of skeletal muscles innervated by the
      affected nerves in diabetic rats. The following groups of rats were investigated:
      24-month-old males that had been diabetic for less than 12 months, 10-month-old
      pre-diabetic males, 24-month-old non-diabetic females, and 10-month-old
      nondiabetic females. The soleus (SOL), extensor digitorum longus (EDL) and biceps
      femoris (BF) muscles were studied by light and electron microscopy, including
      histochemical and morphometric analyses. Muscle weight was reduced with age to a
      remarkable degree in diabetic BF and EDL. Dispersed atrophy of muscle fiber was
      observed in type 2a fibers of BF and EDL, and type 2c fibers of SOL, and the
      incidence was higher in diabetic rats. Multi-core, myofibrillar disorientation
      and an increased number of central nucleus of SOL, along with connective tissue
      proliferation of BF perimysium were noted in diabetic rats. The fiber population
      and type of composition varied with age, but no remarkable changes attributable
      to diabetic conditions were observed. Electron microscopically, an abnormal
      arrangement of myofibrils, a number of myelin figures, mitochondrial swelling and
      lysis of mitochondrial cristae were seen in diabetic rats. However, the
      neuromuscular junction and capillaries were intact. These findings indicate that
      the diabetic skeletal muscle lesion in WBN/Kob rats was mainly myogenic in
      nature, and was aggravated by the age-related change.

PMID- 11585252
TI  - p14ARF protein (FL-132) immunoreactivity in intracranial ependymomas and its
      prognostic significance: an analysis of 103 cases.
AB  - Although clinical and histological criteria for ependymoma prognosis are
      recognized, studies have reported contradictory results. Prognostic significance
      based on immunohistochemistry of ependymomas has been described in a few studies
      and a strong prognostic value of p53 aberrant expression has been established.
      Recently, p53 regulation has found to be dependent on the function of the pl4ARF
      gene product, which has been shown to be critically involved in human
      carcinogenesis. In this study we have examined patients with intracranial
      ependymomas (n=103) for immunoexpression of the novel antibody FL-132 to human
      pl4ARF protein. We found that: (1) the polyclonal FL-132 antibody seems to be
      suitable for studying pl4ARF protein status in routinely processed and paraffin
      embedded specimens; (2) decreasing pl4ARF protein expression is associated with
      patterns of ependymoma biological aggressiveness, i.e., increasing tumor grade,
      elevated growth fraction and p53 protein accumulation; however, there was no any
      association between p14 and MDM2 immunoexpression in ependymomas; (3) although
      the biological events underlying pl4ARF inactivation in ependymal neoplasms are
      still unclear, FL-132 immunohistochemistry appears to be useful for assessing an
      individual prognosis in these tumors; when the p14 score was considered as "high"
      versus "low" (cut-off p14 labeling index at 10%), it represented an independent
      prognostic factor in both univariate and multivariate analyses (hazard ratio 
      3.56; P=0.0003); and (4) most beneficial information for evaluation of malignant
      ependymoma outcome should be elicited from simultaneous immunohistochemical
      investigation of p14 ARF and p53 in tumor specimen.

PMID- 11585253
TI  - Quantitative immunogold study of glucose transporter (GLUT-1) in five brain
      regions of scrapie-infected mice showing obesity and reduced glucose tolerance.
AB  - Distribution of glucose transporter (GLUT-1) in the microvascular endothelium of
      scrapie-infected SJL/J hyperglycemic mice showing clinical signs of scrapie,
      obesity and reduced glucose tolerance was studied in five brain regions: cerebral
      cortex, hippocampus, thalamus, cerebellum and olfactory bulb. Uninfected
      normoglycemic SJL/J mice showing normal glucose tolerance were used as a control.
      Ultrathin sections of brain samples embedded at low temperature in the
      hydrophilic resin Lowicryl K4M were exposed to anti-GLUT-1 antiserum followed by
      gold-labeled secondary antibodies. Labeling density was recorded over luminal and
      abluminal plasma membranes of microvascular endothelial cells. Ultrastructural
      observations revealed attenuation of the microvascular endothelial lining in
      numerous vascular profiles from brain samples of diabetic mice. Morphometric
      analysis revealed significant decreases of the labeling density for GLUT-1 in the
      microvasculature of the thalamus, cerebellum and, to a lesser degree, the
      hippocampus of diabetic mice. No significant differences between diabetic and non
      diabetic, control mice were observed in the microvessels supplying cerebral
      cortex and olfactory bulb. These findings suggest that abnormal glucose
      metabolism, manifested by reduced glucose tolerance and hyperglycemia, leads to
      impaired transvascular glucose transport in some brain regions but not in others,
      presumably disturbing the function of those brain regions supplied by the
      affected blood microvessels.

PMID- 11585254
TI  - Familial frontotemporal dementia and parkinsonism with a novel N296H mutation in
      exon 10 of the tau gene and a widespread tau accumulation in the glial cells.
AB  - We report a 62-year-old Japanese man with familial frontotemporal dementia and a
      novel missense mutation (N296H) in exon 10 of the tau gene. The patient presented
      with frontal signs followed by temporal signs and parkinsonism. The brain showed
      localized frontotemporal lobe atrophy including the precentral gyrus and
      discoloration of the substantia nigra, and revealed severe neuronal loss with
      proliferation of tau-positive protoplasmic astroglia in the affected cerebral
      cortex, tau-positive coiled bodies and threads in the subcortical white matter,
      and tau-positive pretangle neurons in the subcortical and brain stem nuclei.
      There were no tau-positive neurofibrillary tangles, Pick bodies, tuft-shaped
      astrocytes or astrocytic plaques in the cerebral cortex. Immunoelectron
      microscopically, phosphorylated tau accumulated in both neurons and glial cells
      in different modalities, such as glial filaments in protoplasmic astroglia,
      straight tubules in coiled bodies, and free ribosomes in pretangle neurons. These
      findings suggest that tau proteins are not always assembled in abnormal filaments
      such as twisted ribbons, paired helical filaments and straight tubules in neurons
      and glial cells, which have been shown in previous cases with frontotemporal
      dementia and parkinsonism linked to chromosome 17. Immunoblotting of sarkosyl
      insoluble tau exhibited accumulation of four-repeat tau isoforms in the brain.
      The N296H mutation may interfere with the ability of mutated tau to bind with
      microtubules and lead to tau aggregation. Further study is necessary to determine
      whether this mutation can account for the characteristic tau pathology of this
      case.

PMID- 11585255
TI  - Influences of incubation temperature and various saccharides on the production of
      organic acids and gases by gut microbes of rainbow trout Oncorhynchus mykiss in a
      micro-scale batch culture.
AB  - We studied the influence of incubation temperature and additional saccharides on
      the metabolism of hindgut microbes of the rainbow trout Oncorhynchus mykiss in a
      50 microl-scale batch culture system. Intestinal contents of rainbow trout reared
      at 15 degrees C were incubated with glucose, lactosucrose, sodium alginate or
      colloidal chitin (each 10 g/l) at 15 degrees C or 25 degrees C for 12 h. Levels
      of organic acids at 0 h and 12 h of incubation were quantified with HPLC. We also
      monitored gas release from these cultures during incubation. The main product was
      iso-butyric acid, except for the cultures with colloidal chitin where no net
      production of organic acids was observed. We detected higher levels of iso
      butyric acid in cultures with lactosucrose than in the other cultures. Net
      production of this acid was less in cultures with colloidal chitin than in blank
      cultures. The volume of released gas was larger when incubated at 25 degrees C
      than at 15 degrees C. Cultures with colloidal chitin released more gas than blank
      cultures when they were incubated at 15 degrees C. Cultures with sodium alginate
      released less gas than blank cultures irrespective of incubation temperature.
      These results indicate that the hindgut microbes of this carnivorous fish mainly
      produce branched-chain fatty acids, very likely by microbial digestion of
      nitrogenous materials rather than saccharides. However, additional saccharides
      affected production of branched-chain fatty acids. The influence of incubation
      temperature in the present study also suggested that the environmental
      temperature of host fish should affect microbial digestion in the fish gut.

PMID- 11585257
TI  - Selective digesta retention and coprophagy in Brandt's vole (Microtus brandti).
AB  - Digestive performance, gut morphology and rate of digesta passage were measured
      in Brandt's voles (Microtus brandti) offered pelleted diets of low (25% neutral
      detergent fibre) and high (38%) fibre content. Digestion coefficients of dry
      matter, crude fat, crude protein, energy and fibre were all significantly lower
      on the higher fibre diet. Although not significantly higher, dry matter intakes
      were more than maintained when extra cellulose was included in the diet, so that
      intakes of digestible energy were only 22% lower on the higher fibre diet. Total
      length and total gut tissue weight increased significantly, and the length and
      tissue weight of the caecum, proximal colon, and distal colon were significantly
      greater on the higher fibre diet as well. Total tract mean retention time (MRT)
      of a solute marker (Co-EDTA) was significantly greater than that of a particle
      marker (Cr-cell walls) on the lower fibre diet, and in the same direction on the
      higher fibre diet. The ratio of solute to particle MRTs (the solute/particle
      differential retention ratio) was 1.45 on the lower fibre diet and 1.19 on the
      higher fibre diet. There were no significant differences in marker MRTs between
      diets. Examination of marker concentrations in the stomach, small intestine,
      caecum and colon of voles killed at 0.5-h intervals after a pulse dose of Co-EDTA
      indicated that the marker was recycled to the stomach by coprophagy. Thus, as in
      other microtine rodents, an increase in gut capacity, selective digesta retention
      and recycling of digesta via coprophagy enables Brandt's voles to utilise diets
      of higher fibre content than may be expected for such a small (45 g) mammalian
      herbivore.

PMID- 11585256
TI  - Enzymatic digestive activity in Mytilus chilensis (Hupe 1854) in response to food
      regimes and past feeding history.
AB  - Digestive enzyme activities (amylase, cellulase, laminarinase and protease) were
      analysed in mussels (Mytilus chilensis) from intertidal and subtidal habitats in
      Yaldad Bay, Chiloe, Chile. In order to analyse the effects of the past-feeding
      history (origin) and new nutritional conditions (habitat) on these enzymatic
      activities, a cross-over transplant was carried out and the analysis performed
      after a 7-day acclimation period. Crystalline styles showed higher carbohydrase
      and lower protease activities than digestive glands, with the highest differences
      recorded for subtidal mussels. Cellulase is the enzyme with the highest activity
      in both the digestive gland and crystalline style in all the experimental
      conditions. Intertidal mussels transplanted to a subtidal habitat showed enzyme
      resources significantly higher than in their original habitat. In the inverse
      case, mussels transferred from an original subtidal habitat to an intertidal one,
      a significant decrease in carbohydrase and protease activities was observed. The
      "past feeding history' is involved in the specific and total carbohydrase and
      protease activities, with a highly significant effect on amylase and cellulase
      activities in both the crystalline style and the digestive gland. Laminarinase
      activity can be interpreted considering the habitat (trophic regime), either
      individually or interacting with mussels' origin, in relation with the feeding
      periods. The results establish that in M. chilensis, an investment in enzyme
      resources is one of the mechanisms employed to optimise the acclimated response
      in terms of energy gains when variations in the food regime occur.

PMID- 11585258
TI  - The effects of exogenous extracellular carbonic anhydrase on CO2 excretion in
      rainbow trout (Oncorhynchus mykiss): role of plasma buffering capacity.
AB  - The buffering capacity (beta) of rainbow trout (Oncorhynchus mykiss) plasma was
      manipulated prior to intravascular injection of bovine carbonic anhydrase to test
      the idea that proton (H+) availability limits the catalysed dehydration of HCO3-
      within the extracellular compartment. An extracorporeal blood shunt was employed
      to continuously monitor blood gases in vivo in fish exhibiting normal plasma beta
      (-3.9+/-0.3 mmol 1(-1) pH unit(-1)), and in fish with experimentally (using N-[2
      hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid]) elevated plasma beta (-12.1+/
      1.1 mmol 1(-1) pH unit(-1)). An injection of 5 mg kg(-1) carbonic anhydrase
      equally reduced (after 90 min) the arterial partial pressure of CO2 in trout with
      regular (-0.23+/-0.05 Torr) or high (-0.20+/-0.05 Torr) plasma beta; saline
      injection was without effect. Because ventilation and venous blood gases were
      unaffected by carbonic anhydrase, the effect of extracellular carbonic anhydrase
      in lowering arterial partial pressure of CO2 was likely caused solely by a
      specific enhancement of CO2 excretion owing to acceleration of HCO3- dehydration
      within the plasma. The lowering of arterial partial pressure of CO2 in trout
      after injection of exogenous carbonic anhydrase provides the first in vivo
      evidence that the accessibility of plasma HCO3- to red blood cell carbonic
      anhydrase constrains CO2 excretion under resting conditions. Because the velocity
      of red blood cell Cl-/HCO3- exchange governs HCO3- accessibility to red blood
      cell carbonic anhydrase, the present study also provides evidence that CO2
      excretion at rest is limited by the relatively slow rate of Cl-/HCO3- exchange.
      The effect of carbonic anhydrase in lowering arterial partial pressure of CO2 was
      unrelated to plasma buffering capacity. While these data could suggest that H+
      availability does not limit extracellular HCO3- dehydration in vivo at resting
      rates of CO2 excretion, it is more likely that the degree to which plasma beta
      was elevated in the present study was insufficient to drive a substantially
      increased component of HCO3- dehydration through the plasma.

PMID- 11585259
TI  - Are summit metabolism and thermogenic endurance correlated in winter-acclimatized
      passerine birds?
AB  - Small birds exhibiting marked winter improvement of cold tolerance also show
      elevated summit metabolic rates (maximum cold-induced metabolic rate) in winter
      relative to summer. However, relatively large increases in cold tolerance can
      occur with only minor increments of maximum cold-induced metabolic rate and
      geographic variation in cold tolerance is not always positively correlated with
      variation in maximum cold-induced metabolic rate. Thus, it is uncertain whether
      maximum cold-induced metabolic rate and cold tolerance are phenotypically
      correlated in small birds and no previous study has directly examined this
      relationship. I measured maximum cold-induced metabolic rate and cold tolerance
      (i.e., thermogenic endurance) over three winters in black-capped chickadees
      Poecile atricapillus, American tree sparrows Spizella arborea, and dark-eyed
      juncos Junco hyemalis. For raw thermogenic endurance data, residuals of maximum
      cold-induced metabolic rate and thermogenic endurance from mass regressions were
      significantly and positively correlated in juncos and tree sparrows, and their
      correlation approached significance for chickadees. Log10 transformation of
      thermogenic endurance and mass data gave similar results. These data provide the
      first direct evidence for a phenotypic correlation between maximum cold-induced
      metabolic rate and thermogenic endurance in small birds, although much of the
      variance in thermogenic endurance is explained by factors other than maximum cold
      induced metabolic rate and the degree of correlation differs among species.
      Nevertheless, these data suggest that physiological adjustments producing
      elevated thermogenic endurance also produce elevated maximum cold-induced
      metabolic rate in small birds.

PMID- 11585260
TI  - Ventilation, gill perfusion and blood gases in dourado, Salminus maxillosus
      Valenciennes (teleostei, characidae), exposed to graded hypoxia.
AB  - The dourado, Salminus maxillosus, is an active and migratory teleost found in
      lotic waters of Southern Brazil. We have studied the relationships of gas
      transport in dourado to the specific ecophysiology of this-species. Measurements
      were performed of blood gases, O2 uptake, gill ventilation and perfusion at
      normoxia and various levels of hypoxia. Thus, the study aimed at a detailed
      assessment of the causes of O2 transport failure, using recent models for gas
      transport in vertebrates. Oxygen uptake was maintained down to a critical water
      partial O2 pressure of 42 mmHg, below which it markedly decreased. This could be
      explained based on ventilatory and cardiovascular responses: Ventilation
      increased sufficiently to match decreases of water O2 partial pressure during
      moderate hypoxia (partial pressure of O2 > 42 mmHg) but failed to meet O2 demands
      below this value. Likewise, the cardiovascular responses were insufficient to
      maintain an adequate transport below moderatelevels of hypoxia. Thus, combined
      failure of ventilation and blood gas transport account for the abrupt decreases
      of O2 transport. The species proved highly vulnerable to hypoxia, which is
      consistent with the normally well-aerated habitat and the active mode of life of
      the species.

PMID- 11585261
TI  - Melatonin potentiates the vasoconstrictive effect of noradrenaline in renal
      artery from newborn hooded seals (Cystophora cristata) and harp seals (Phoca
      groenlandica).
AB  - Isometric tension was recorded by force displacement transducers in ring segments
      of the inferior branch of the renal artery from newborn hooded seals (Cystophora
      cristata, n=6), harp seals (Phoca groenlandica, n=3) and domestic pigs (Sus
      scrofa f. domestica, n=5). Arterial segments were mounted in heated organ baths
      and exposed to graded concentrations of noradrenaline (NA) and adrenaline (A),
      alone or together with melatonin. The melatonin concentration in the bath was
      similar to the plasma concentration normally found in each experimental animal.
      Melatonin alone did not affect the tension in any of the species, but melatonin
      potentiated the contraction induced by NA in hooded and harp seal arteries to a
      maximum of about 25% above the resting, pre-stretch level. The selective
      melatonin receptor antagonist luzindole reduced this potentiation by 80%. Species
      specific concentrations of melatonin did not potentiate the NA-effect in the
      domestic pig or the A-induced contraction in any of the species. The results
      indicate that melatonin specifically increases the NA-sensitivity of smooth
      muscles in renal arteries from newborn seals. It is presumed that similar effects
      may operate in foetal and maternal seals and may influence their circulation
      during maternal diving.

PMID- 11585262
TI  - Energetics of foraging and locomotion in the platypus Ornithorhynchus anatinus.
AB  - We measured the energy requirements of platypuses foraging, diving and resting in
      a swim tank using flow-through respirometry. Also, walking metabolic rates were
      obtained from platypuses walking on a conventional treadmill. Energy requirements
      while foraging were found to depend on water temperature, body weight and dive
      duration and averaged 8.48 W kg(-1). Rates for subsurface swimming averaged 6.71
      W kg(-1). Minimal cost of transport for subsurface swimming platypuses was 1.85 J
      N(-1)m(-1) at a speed of 0.4 m s(-1). Aerobic dive limit of the platypus amounted
      to 59 s. Metabolic rate of platypuses resting on the water surface was minimal
      with 3.91 W kg(-1) while minimal RMR on land was 2.08 W kg(-1). The metabolic
      rate for walking was 8.80 W kg(-1) and 10.56 W kg(-1) at speeds of 0.2 m s(-1)
      and 0.3 m s(-1), respectively. A formula was derived, which allows prediction of
      power requirements of platypuses in the wild from measurements of body weight,
      dive duration and water temperature. Platypuses were found to expend energy at
      only half the rate of semiaquatic eutherians of comparable body sizes during both
      walking and diving. However, costs of transport at optimal speed were in line
      with findings for eutherians. These patterns suggest that underwater locomotion
      of semiaquatic mammals have converged on very similar efficiencies despite
      differences in phylogeny and locomotor mode.

PMID- 11585263
TI  - Heterothermic responses in the speckled mousebird (Colius striatus).
AB  - We investigated normothermic thermoregulation and heterothermic responses to
      restricted food in the speckled mousebird Colius striatus, in the context of the
      widely accepted distinction between normothermia, rest-phase hypothermia, and
      torpor. Normothermic thermoregulation differed from typical endothermic patterns
      in that rest-phase body temperature (Tb) was not maintained with respect to a
      constant setpoint. Instead, Tb decreased during the course of the rest-phase,
      with the highest cooling rates observed at moderate ambient temperatures (Ta).
      Restricted food was associated with significant reductions in rest-phase Tb and
      metabolic rate. The lowest Tb recorded in a bird which was able to arouse
      spontaneously, was 18.2 degrees C. However, we were unable to clearly discern
      between normothermic, hypothermic and torpor Tb ranges. Furthermore,
      heterothermic responses did not accord with the patterns typically observed in
      birds and mammals. Metabolic suppression normally associated with entry into
      torpor and the defence of a torpor Tb setpoint was largely absent. The mousebirds
      significantly reduced their energy expenditure when heterothermic at moderate TaS
      only. We suggest that the observed patterns of thermoregulation in C. striatus,
      as well those previously reported in Colius colius, are associated with
      plesiomorphic clustering behaviour in the Coliiformes, and the tandem evolution
      of behavioural and metabolic thermoregulation.

PMID- 11585264
TI  - Effects of different steroid-biosynthesis inhibitors on the testicular
      steroidogenesis of the toad Bufo arenarum.
AB  - Testis fragments from Bufo arenarum were incubated with [7(n)-(3)H]pregnenolone
      (P5), [1,2-(3)H]dehydroepiandrosterone (DHEA) and [1,2,6.7-(3)H]testosterone (T),
      and different steroid-biosynthesis inhibitors. The inhibitors used were:
      cyanoketone (CNK), spironolactone (SPNL) and finasteride (FIN). CNK significantly
      increased the recovery of 3beta-hydroxy-5-ene steroids while SPNL reduced the
      metabolism of P5 and the production of C19-steroids. The metabolism of C19
      substrates was only modified by CNK, which reduced the transformation of DHEA
      without modifying the metabolism of T. To determine the degree of inhibition
      exerted by the inhibitors used, the activities of the enzymes were estimated as
      the percentage of their contribution to the total steroid metabolism. CNK
      strongly inhibited the activity of hydroxysteroid dehydrogenase/isomerase if its
      contribution was estimated using both P5 and DHEA. If the analysis was made
      considering both activities associated to cytochrome P450 17chi-hydroxylase, C17
      20 lyase (P450c17), it became evident that SPNL inhibited both of them. The
      percent contribution of 17beta-hydroxysteroid dehydrogenase (17betaHSD) activity
      diminished in the presence of CNK only if it was estimated considering P5 and
      DHEA metabolism. SPNL produced a significant inhibition of 17betaHSD when its
      contribution was estimated considering P5 metabolism. However, SPNL was
      insufficient if DHEA or T were considered. The effect of SPNL on the contribution
      of 17betaHSD could be due to the reduction of C19-substrates. The activity of
      5chi-reductase was inhibited by CNK only if results from P5 and DHEA were
      considered.

PMID- 11585265
TI  - Progress in palliative care.

PMID- 11585266
TI  - Terminal sedation in palliative medicine--definition and review of the
      literature.
AB  - This paper reviews the reported use of nonopioid medications for terminal
      sedation. To provide a summary of the available literature, an electronic
      database search was performed. Thirteen series and 1 4 case reports were
      identified. Various symptoms, including agitation, pain, and confusion, required
      terminal sedation. Eleven drugs were used in 342 patients. Most patients were
      also treated with concurrent opioids and received terminal sedation in an
      inpatient hospice unit. Midazolam was the most common sedative employed. A good
      response--defined as adequate sedation--ranged between 75% and 100%. The median
      time to death following the introduction of terminal sedation was greater than 1
      day. No agent appears to have superior efficacy or limiting toxicity.

PMID- 11585267
TI  - Evaluation and treatment of cancer-related fluid deficits: volume depletion and
      dehydration.
AB  - Fluid deficits should be divided into two categories (dehydration and volume
      depletion) according to pathophysiology and into 3 categories (hyponatremic,
      hypernatremic, and isotonic) according to the plasma sodium concentration.
      Dehydration (total water deficit especially intracellular) is always
      hypernatremic, while volume depletion (intravascular water and sodium deficit) is
      either hyponatremic, hypernatremic, or isotonic. There are no clear clinical
      differences among the various categories, but a delay of capillary refill,
      tachycardia, and orthostatic hypotension are more common with early volume
      depletion. An Evans blue and mannitol test can be used to distinguish between
      hypernatremic volume depletion and dehydration. Careful clinical assessment and
      laboratory tests (especially serum sodium) are the key to diagnosis and effective
      management. According to the type (hypernatremic, hyponatremic, or isotonic),
      severity of fluid deficit, and associated symptoms, oral or parenteral fluid
      should be given along with treatment of the underlying cause. In hemodynamically
      compromised individuals with orthostatic hypotension and oliguria, replacement
      with isotonic saline until hemodynamic stabilization is crucial. Terminal
      hydration is still controversial. Important ethical principles govern clinical
      decision-making about hydration at the end of life.

PMID- 11585268
TI  - Communication with terminal cancer patients in palliative care: are there
      differences between nurses and physicians?
AB  - The aim of this study was to find whether there were interprofessional
      differences in specific elements of communication with terminal cancer patients
      and decision-making processes that concern such patients. Given that
      interdisciplinary team work is one of the basic values in palliative care, if
      there are conflicting views between professions on such important issues it is
      most important to know about these and to understand them. A questionnaire
      utilized in an earlier survey of palliative care physicians and addressing their
      attitudes to and beliefs about specific elements of communication and decision
      making was sent to a sample of palliative care nurses working in the same
      regions, i.e. the French-speaking parts of Switzerland, Belgium and France. After
      a second mailing (reminder), 135 of the 163 questionnaires (83%) were returned.
      There was general agreement between nurses and physicians on questions dealing
      with perceptions of patients' knowledge of their diagnosis and stage of disease,
      patients' need for information, "do not resuscitate" orders and ethical
      principles in decision-making processes. Statistically significant, but small,
      differences between professional groups were only observed for a minority of the
      questions. Interprofessional differences in specific elements of communication
      with terminal cancer patients and decision-making processes affecting these
      patients were not so marked that they could be called "conflicting
      interprofessional views."

PMID- 11585269
TI  - Assessment of pain control in cancer patients during the last week of life:
      comparison of health centre wards and a hospice.
AB  - The aim of this prospective study was to assess the quality of cancer pain
      control during the last week of life in two different types of units for terminal
      cancer patients in Finland: on health centre wards (N=20) and in a hospice
      (N=30). Pain scores (VAS), defined daily doses (DDD), routes of administration
      and costs of pain medication were analysed for each patient. On the 7th-last day
      before death and during the very last day of life (24 h), respectively, the
      following results were seen: proportions of patients using strong opioids 64% and
      84%, mean equivalent parenteral morphine doses of strong opioids 42 mg and 57 mg,
      mean pain scores (VAS 0-10) 3.11 and 3.05, mean daily cost of pain medication
      2.22 and 2.90 euros. Pain control was thus found to be good with low costs. On
      the 7th day before death strong opioids were used for a greater proportion of
      patients on the health centre wards. Differences were also seen in the routes of
      administration used for strong opioids. Weak opioids were used more in the
      hospice and NSAIDs, more on the health centre wards. However, no differences were
      found either in the mean doses of strong opioids or in the quality or the costs
      of pain control between the health centre wards and the hospice.

PMID- 11585271
TI  - The importance of cytochrome P450 monooxygenase CYP2D6 in palliative medicine.
AB  - The enzymes in the cytochrome p450 monooxygenase system (CYP) are the major
      enzymes responsible for metabolizing medications. The CYP2D6 isomer is
      responsible for metabolizing certain opioids, neuroleptics, antidepressants and
      cardiac medications. Owing to CYP2D6's low capacity and high affinity it is
      easily saturated by substrate and/or inhibited, resulting in pharmacokinetic
      interactions. Polymorphisms of the structural gene are common, leading to wide
      inter-individual and ethnic differences in drug metabolism. Clinically important
      drug interactions, which may be anticipated in the palliative medicine
      population, are reviewed.

PMID- 11585270
TI  - Gender discrepancy observed between chemotherapy-induced emesis and hiccups.
AB  - The aim of this paper was to describe striking gender differences observed
      between emesis and hiccups in patients receiving cisplatin-based chemotherapy
      (CT) and one of two dexamethasone-containing anti-emetic regimens. Four hundred
      patients were evaluated in a crossover study with two arms. Patients in arm A
      received three doses of ondansetron 8 mg i.v. at 4-h intervals plus dexamethasone
      20 mg i.v. from the start of CT, followed by dexamethasone 5 mg i.v. every 12 h,
      until CT was complete, after which dexamethasone was discontinued. For patients
      in arm B the treatment was the same as in arm A except that the three doses of
      ondansetron 8 mg i.v. were given at 24-h intervals. There were 363 patients in
      arm A and 358 patients in arm B. Vomiting/nausea/hiccups were observed in
      30.3%/41.6%/23.7% of patients in arm A and 28.8%/39.1%/23.7% of patients in arm
      B, respectively. Comparison showed that the rates for complete control of
      vomiting and nausea on days 1 through 6 were significantly lower in women
      (P<0.0001 and =0.0004 in arm A and P<0.0001 and <0.0001 in arm B, respectively).
      Men had a significantly higher incidence of hiccups (P<0.0001 in both arms), but
      no apparent associations with age, cisplatin dose, tumor type, and the presence
      of vomiting and nausea during CT were found. Hiccups usually began 24 h after
      cisplatin administration and persisted for some days. Women had significantly
      higher rates of vomiting and nausea. The cause of the gender discrepancy is
      unknown.

PMID- 11585272
TI  - Factors associated with utilization of nonproven cancer therapies in Turkey. A
      study of 135 patients from a single center.
AB  - In their search for a cure, a significant number of cancer patients use nonproven
      treatment (NPT) methods. However, little is known about patient and disease
      characteristics associated with the use of these methods. In this trial, we
      evaluated the prevalence of and the factors associated with the usage of
      nonproven cancer remedies in a teaching hospital in Turkey. A self-administered
      questionnaire was given to 135 cancer patients attending the outpatient clinics
      of a medical oncology department. Patients' demographic data, their usage of
      nonproven methods, and possible contributing factors were explored. Our cohort
      mainly comprised poor patients with only primary school education. Overall, 50%
      of our patients had used or were using NPT methods. Medicinal herbs (mainly
      stinging nettle) were the most frequently used remedy. In contrast, such
      "complementary therapies" as exercise, relaxation, and meditation were not
      employed. In multivariate analysis, only duration of disease was found to be
      significantly associated with NPT utilization [P=0.05, relative risk (RR)=1.94].
      In addition, patient education level was marginally significant (P=0.07,
      RR=0.36). Apart from long duration of disease and being better educated, no other
      clinical, social, economic and cultural factors evaluated were associated with
      the use of NPT in our group of Turkish patients. Since these treatments are
      sometimes costly and have questionable efficacy and toxicity, proper scientific
      trials are needed to clarify whether such methods have a real role in cancer
      management.

PMID- 11585273
TI  - Difference in patient's acceptance of early versus late initiation of
      psychosocial support in breast cancer.
AB  - The present study was performed to assess the difference in acceptance of
      psychosocial counseling and resulting benefits between patients with breast
      cancer with early or late onset. In a prospective randomized controlled study
      conducted over 6 months, 41 women with a new diagnosis of early breast cancer
      (group 1) and 43 patients with advanced breast cancer (group 2) received
      individually tailored psychosocial support and were compared against controls.
      This therapy was free of charge, and the duration of support was determined by
      the patients' wishes and needs. Among the patients with new onset of disease
      acceptance of the psychosocial counseling was high, and these patients
      experienced significant improvements in their quality of life. In contrast,
      acceptance of psychosocial counseling was low in the advanced breast cancer group
      and the therapy did not improve quality of life over the observation period of 6
      months. Early psychosocial support in patients with breast cancer meets with a
      high acceptance rate and improves quality of life.

PMID- 11585274
TI  - Anticancer chemotherapy in a patient with prior history of acute intermittent
      porphyria. A case report and review of the literature.
AB  - We describe the case of a patient with a prior history of acute intermittent
      porphyria (AIP) who needed the administration of anticancer drugs. Our experience
      with this patient and the limited experience reported in the literature show that
      it is probably safe to administer some chemotherapeutic agents, but it is
      important to prevent (or to minimize) the toxicities of these chemotherapeutic
      agents, as they seem to put the patient at major risk of an AIP crisis. Hematin
      and supportive treatments were useful treatments in our patient.

PMID- 11585275
TI  - Rifampicin in opioid-induced itching.
AB  - Pruritus is prevalent in 5-12% of palliative care patients. Rifampicin has been
      shown to be useful both as initial treatment and as salvage treatment after
      failure of other agents to control the pruritus associated with the cholestatic
      jaundice of malignancy. We report the case of a 65-year-old woman who complained
      of severe pruritus after morphine treatment. The use of rifampicin 300 mg twice a
      day by the i.v. route was successful, and after opioid switching it was no longer
      necessary to maintain rifampicin in the therapeutic regimen. Controlled clinical
      trials are warranted to confirm this preliminary observation.

PMID- 11585276
TI  - Mirtazapine may be useful in treating nausea and insomnia of cancer chemotherapy.
AB  - Mirtazapine is an antidepressant that has a receptor-binding profile that may
      suit it for use in controlling the nausea and insomnia of highly emetic cancer
      chemotherapy. Mirtazapine binds to and is antagonistic at the 5HT3 receptor, as
      are the group of medicines related to ondansetron. Mirtazapine is anxiolytic by
      virtue of its antagonism of the 5HT2 receptor, and is strongly sleep inducing.
      The resulting sleep quality tends to be superior to that induced by
      benzodiazapines. There has been concern about mirtazapine's potential to suppress
      bone marrow function, so that further study is required before routine use in
      chemotherapy can be adopted.

PMID- 11585277
TI  - Renal cortical calcification in syngeneic intact rats and those receiving an
      infrarenal thoracic aortic graft: possible etiological roles of endothelin,
      nitrate and minerals, and different preventive effects of long-term oral
      treatment with magnesium, citrate and alkali-containing preparations.
AB  - Renal cortical nephrocalcinosis (C-NC) is a rare disorder of uncertain etiology.
      Using highly inbred (syngeneic) male Lewis rats, we describe the spontaneous
      occurrence of histologically detectable C-NC in sham operated control rats (Sham;
      n=12), its aggravation following grafting of the ascending thoracic aorta from a
      donor rat to the infrarenal aorta of a recipient (ATx; n=12), and differences in
      C-NC inhibition after 12 weeks of oral administration of magnesium (Mg), citrate
      and alkali. C-NC is characterized by Kossa-positive areas located in cells of the
      proximal tubule close to blood vessels and also, to a lesser extent, within
      glomeruli. After ATx there was vascular overproduction of endothelin (ET-1) but
      decreased production of nitrate; in renal cortical tissue there was an excess of
      calcium over Mg and phosphorus and oxalate over citrate. In plasma there was an
      increase in calcium and creatinine within the normal range. Calcification of
      tubular cells was eliminated by a preparation containing potassium, sodium and
      bases (from citrate degradation and bicarbonate) in addition to Mg. Less
      effective than the latter was Mg-potassium citrate and least effective, Mg
      citrate. The former treatment also normalized calcemia and urinary nitrate, but
      only incompletely suppressed ET-1 and had no significant effect on glomerular
      calcification or tissue and urinary oxalate. Urinary ET-1 excess appeared
      directly related to the cortical tissue calcium/Mg ratio, and urinary excretion
      of Mg, citrate and total protein appeared to be inversely related to the severity
      of C-NC. It was concluded that (1) the highly inbred rat is prone to
      precipitation of calcium phosphate in the renal cortex; (2) this type of C-NC
      occurs in close proximity to and within renal vascular tissue and is associated
      with an imbalance of vasoconstrictors and vasodilators of endothelial origin; (3)
      effective inhibition of C-NC can be achieved by an alkalinizing combination of
      Mg, potassium, sodium and citrate, underscoring its utility in the prophylaxis of
      pathological calcium phosphate deposition. The significance of these findings for
      the etiology and treatment of clinical disorders with renal and vascular
      calcification is uncertain and requires further investigation.

PMID- 11585278
TI  - Evidence suggesting that high intake of fluoride provokes nephrolithiasis in
      tribal populations.
AB  - The present study was designed to evaluate the role of fluoride in urolithiasis
      in humans. Two areas were selected for this purpose, a fluoride endemic area (EA)
      and a fluoride non-endemic area (NEA). The prevalence of uroliathiasis was 4.6
      times higher in EA than in NEA. Furthermore, the prevalence was almost double in
      subjects with fluorosis than without fluorosis in the endemic area. No
      relationship was observed between urolithiasis and the duration of fluorosis. The
      fluoride levels in drinking water ranged from 3.5 to 4.9 ppm in EA and subjects
      from this area excreted more fluoride. A comparison of normal subjects (NS) from
      EA and NEA revealed that endemic subjects tend to have slightly higher mean serum
      thiobarbituric acid reactive substance (TBAR) levels and excrete more oxalate and
      fluoride than their non-endemic counterparts. The urinary stone formers (SF) from
      the two areas showed a similar tendency, though again the difference was not
      significant. Citrate excretion in SF was almost normal in the EA, but NEA SF had
      significantly lower excretion levels. Urinary stones from endemic patients had
      higher fluoride, oxalate and calcium levels than those from non-endemic patients.
      In vitro studies suggested that fluoride did not influence the heterogonous
      mineralization of calcium oxalate. In conclusion, the data suggest that fluoride
      in vivo may behave as a mild promoter of urinary stone formation by (a) excretion
      of insoluble calcium fluoride, (b) increasing oxalate excretion and (c) mildly
      increasing the oxidative burden.

PMID- 11585279
TI  - Urinary oxalate excretion in female calcium oxalate stone formers with and
      without a history of recurrent urinary tract infections.
AB  - Therapy with antibiotics in recurrent urinary tract infections may destroy
      colonies of Oxalobacter formigenes in the intestinal tract. A lack of oxalate
      degradation caused by the absence of this bacterium is suggested to contribute to
      the hyperabsorption of dietary oxalate and to the increase in urinary oxalate
      excretion. The present study was performed to evaluate the effect of recurrent
      urinary tract infections and subsequent changes induced in the urinary excretion
      profile in female calcium oxalate stone formers. Serum biochemical profiles, 24-h
      urinary parameters, and the personal characteristics of 57 female calcium oxalate
      stone patients with recurrent urinary tract infections (RUTI) were compared with
      78 female calcium oxalate stone patients without a history of urinary tract
      infection. All subjects were recruited during the same period. In female patients
      with RUTI, urinary oxalate excretion was significantly higher (0.374 mmol/day)
      than in females without urinary tract infection (0.308 mmol/day) (P < 0.05).
      Moreover, the mean 24-h pH value and urinary sodium excretion were significantly
      higher in women with RUTI than in women without a history of urinary tract
      infection. The significantly higher urinary oxalate excretion in female calcium
      oxalate stone formers with recurrent urinary tract infections may be associated
      with the application of antibiotics and a subsequent temporary or permanent
      decolonization of Oxalobacter formigenes.

PMID- 11585280
TI  - Video cystometry in young infants with renal dilation or a history of urinary
      tract infection.
AB  - Cystometry is increasingly being used in infants to diagnose bladder dysfunction.
      However, infantile urodynamic patterns have not been fully established. In this
      study we investigated the urodynamic patterns in young infants with renal
      dilation or a history of urinary tract infection, but with no apparent lower
      urinary tract symptoms. We use video cystometry with simultaneous perineal EMG
      recording. Thirty-five infants (27 male and 8 female) with congenital renal
      dilatation or a history of urinary tract infection at age 2 days to 24 months old
      were involved. We found that detrusor instability occurred in 8.6% of these
      subjects. Bladder capacity increased with age but less than would nomally be
      expected. An intermittent voiding pattern was observed in 57% (20/35) of subjects
      and was characterized by a single or recurring increase in sphincter activity
      with a simultaneous rise in the voiding detrusor pressure curve. The maximum
      voiding detrusor pressure with pelvic floor overactivity was significantly higher
      than that with no pelvic floor overactivity (105+/-44 cmH2O vs 69+/-22 cmH2O, P <
      0.001). The median post-voiding residual volume was 2 (range 0 to 65) ml. We
      conclud that in infants with no apparent lower urinary tract symptoms, bladder
      instability is uncommon, and the capacity is lower than the normally expected
      range; an intermittent voiding pattern is common and the residual urine volume
      showed great variation. This probably represents an immature detrusor-sphincter
      function.

PMID- 11585281
TI  - Covering of the terminal ureter with de-serosalized muscle layer of the ileum for
      antireflux ureteroileostomy: an experimental study in dogs and a preliminary
      clinical trial.
AB  - We demonstrated a new operative technique for antireflux ureteroileostomy in
      dogs. The severed ureter was reimplanted into the isolated ileum. Ten terminal
      ureters were covered with a 2 x 2 cm2 section of de-serosalized ileal wall after
      direct ureteroileostomy, and another six terminal ureters were covered with a 2 x
      2 cm2 section of non-de-serosalized full-thickness ileal wall. Thirteen ureters
      were directly anastomosed to the ileum without any additional procedures. The
      bladder was augmented by the detubularized ileum with the ureter. Postoperative
      evaluations on ureteral stenosis and reflux were performed monthly for 3 months.
      The ureters covered with the de-serosalized ileal wall prevented ureteral reflux
      even when the intravesical pressure climbed as high as 100 cm H2O. Although two
      of these ten ureters demonstrated strictures at the precise site of direct
      ureteroileostomy, the sections of the ureters covered with the de-serosalized
      ileal wall were opened and did not collapse. In the resected specimens, the
      terminal ureters were found in the intramural part of the ileum. The ureters
      covered with the full-thickness of ileal wall did not prevent reflux. Our method
      of covering the terminal ureter with the de-serosalized ileal wall worked well as
      an antireflux mechanism, and the intramural ureter did not cause ureteral
      stricture. After this animal experiment, we introduced this antireflux mechanism
      clinically.

PMID- 11585282
TI  - Morphological examination of the effects of defibrotide on experimentally induced
      bladder injury and its relation to interstitial cystitis.
AB  - This morphological study aims to investigate the effects of defibrotide, a
      deoxyribonucleic acid derivative drug with cytoprotective, immunosuppressive and
      vasorelaxant effects, on protamine sulfate induced bladder injury. Wistar albino
      female rats were catheterized and intravesically infused with phosphate buffered
      solution (control group) or, either protamine sulfate (bladder injury group) or
      protamine sulfate+defibrotide (bladder injury+defibrotide group) dissolved in
      phosphate buffered solution. The morphology of the urinary bladder was
      investigated using light and electron microscopy. The number of mast cells in the
      mucosa, mucosal alterations, intercellular junctions, surface topography and the
      glycosaminoglycan (GAG) layer as well as microvillus formation on the luminal
      surface were evaluated. In the bladder injury group, ulcerated areas,
      irregularity of the GAG layer, increased number of mast cells, vacuole formation,
      dilated perinuclear cistern, formation of pleomorphic and uniform microvilli and
      dilatations in the intercellular spaces in the urothelium were observed. In the
      bladder injury+defibrotide group a relatively normal urothelial topography, GAG
      layer and a few mast cells in the mucosa, some dilatations between the
      intercellular areas, less uniform microvilli, regular perinuclear cistern and
      tight junctions were observed. These results show that defibrotide can inhibit PS
      induced bladder damage.

PMID- 11585283
TI  - Simultaneous monitoring of extracellular glucose, pyruvate, and lactate in rat
      testies during ischemia: a microdialysis study.
AB  - A dual-probe microdialysis technique was developed for the simultaneous
      monitoring of glucose and related metabolite levels during testicular ischemia in
      rats. The determinations of lactate and pyruvate were achieved by liquid
      chromatography within 5 min. Glucose was determined by a microdialysis analyzer.
      A unilateral ligation was produced by occlusion of the right artery for 2 or 4 h
      in anesthetized rats. Microdialysis probes were inserted in both sides of the
      testis to simultaneously monitor glucose, lactate and pyruvate during basal,
      ischemia and reperfusion periods. Dynamic and comparative changes in these
      analytes in ipsilateral and contralateral testes were demonstrated. The present
      technique can be used as a tool for exploring energy related metabolites and
      their relationships in testicular ischemia.

PMID- 11585284
TI  - Dehydroepiandrosterone in the treatment of erectile dysfunction in patients with
      different organic etiologies.
AB  - In 1994 the Massachusetts Male Aging Study described an inverse correlation of
      the serum levels of dehydroepiandrosterone sulfate (DHEAS) and the incidence of
      erectile dysfunction (ED). The positive results of a pilot study in the treatment
      in patients with no organic etiology prompted a detailed investigation on the
      efficacy of DHEA therapy for ED in patients with different organic etiologies, in
      a prospective study. The inclusion criteria included ED, a normal physical
      condition, normal serum levels of testosterone, prolactin and PSA and a serum
      DHEAS level < 1.5 micromol/l. The study patients comprised 27 patients (group 1)
      with hypertension, 24 patients (group 2) with diabetes mellitus, six patients
      with neurological disorders (group 3) and 28 patients (group 4) with no organic
      etiology were treated with 50 mg DHEA p.o. for 6 months. We assessed efficacy by
      using the responses to question 3 (frequency of penetration) and question 4
      (maintenance of erections after penetration) of the 15-question International
      Index of Erectile Function (IIEF). DHEA treatment was associated with
      statistically significantly higher mean scores compared to baseline values for
      question 3 and question 4 of the IIEF in groups 1 and 4 after a period of 24
      weeks. The differences between the mean scores of groups 2 and 3 and the baseline
      values were not statistically significant. Our results suggest that oral DHEA
      treatment may be of benefit to patients with ED who have hypertension or to
      patients with ED without organic etiology. There was no impact of DHEA therapy on
      patients with diabetes mellitus or with neurological disorders.

PMID- 11585285
TI  - The effect of osteopontin immobilized collagen granules in the seed crystal
      method.
AB  - Osteopontin (OPN) is a urinary protein which inhibits calcium oxalate (CaOx)
      crystal growth in the seed crystal system. The aim of this study was to evaluate
      the effects of OPN immobilized on collagen granules (CG) for CaOx crystal growth
      and aggregation in this system. OPN-immobilized CG showed a 30% decrease in
      inhibitory activity compared with non-OPN-immobilized CG. Scanning electron
      microscopy revealed that 1) OPN-immobilized CG showed more marked aggregation and
      adhesion of seed crystals (smaller than 0.5 microm in diameter) than non-OPN
      immobilized CG, 2) the amount of adherent large type crystals (2-3 microm in
      diameter) did not differ between OPN immobilized and non-OPN-immobilized CG. In
      conclusion, immobilized OPN promotes aggregation and adhesion of CaOx crystals
      smaller than 0.5 microm on CG. These observations suggest that crystal adhesion
      to immobilized OPN plays a role in the retention of crystals in the kidney.

PMID- 11585286
TI  - E-cadherin expression and PSA secretion in human prostate epithelial cells.
AB  - Prostate-specific antigen (PSA) is the most widely used marker for the diagnosis
      of prostate cancer and is an independent predictor of prostatic capsular
      invasion. A number of studies have identified E-cadherin, a cell adhesion
      protein, as a potential invasion suppressor which is decreased in prostate
      adenocarcinoma. Our goal in the present study was to evaluate E-cadherin
      expression in primary cultures and determine the relationship between E-cadherin
      expression and PSA secretion in both primary cultures and the prostate tumor cell
      line, LNCaP. Immunohistochemical studies and Western blot analysis confirmed
      greater expression of E-cadherin in normal epithelial cells than tumor-derived
      prostate cells. This is the first report that the incubation of normal prostate
      epithelial cells with E-cadherin antibody increases the amount of PSA detected in
      the media of normal cells as well as in LNCaP. Since E-cadherin may function as
      an invasion suppressor, an understanding of the decreased expression of this
      adhesion factor and the impact on PSA secretion may aid in understanding
      epithelial tumorigenesis.

PMID- 11585287
TI  - The prognostic value of myocardial perfusion scintigraphy: investigators, are you
      (mis)leading us?

PMID- 11585288
TI  - Anti-angiogenic therapy and radioimmunotherapy in colon cancer xenografts.
AB  - Angiogenesis is critical to the growth and metastatic process of malignant
      tumors. An endogenous estrogen metabolite, 2-methoxyestradiol (2-ME), displays
      anti-angiogenic and anti-tumorigenic effects. The purpose of this investigation
      was to determine whether exogenously administered 2-ME would enhance the efficacy
      of radioimmunotherapy (RIT). Experimental RIT with 4.63 MBq of 131I-A7, an IgG1
      anti-colorectal monoclonal antibody, was conducted in mice xenografted with LS
      180 human colon cancer cells. 2-ME suspended in 0.5% carboxymethylcellulose was
      administered daily at a dose of 75 mg/kg per day. 2-ME administration suppressed
      tumor growth and improved the efficacy of RIT in comparison to RIT alone. Tumor
      volumes on day 13, expressed as a ratio relative to the initial volume, were 12.7
      +/- 2.95 in the nontreated control, 4.73 +/- 0.89 with 2-ME, 3.05 +/- 0.37 with
      RIT and 0.97 +/- 0.20 with RIT+2-ME. Immunohistochemistry of tumor sections
      stained with an antibody against factor VIII demonstrated a decrease in
      microvessel number within tumors treated with 2-ME (7.9 +/- 0.8/200x field) as
      compared with that in control tumors (29.9 +/- 2.5). Cell proliferation assay at
      increasing concentrations of 2-ME showed direct cytotoxicity of 2-ME in vitro at
      5 microM and greater. In conclusion, 2-ME enhanced the efficacy of RIT with 131I
      A7 via inhibition of angiogenesis within the xenografts. The direct cytotoxicity
      of 2-ME appears to have contributed to this improvement. Anti-angiogenic therapy
      may prolong the dormancy of microscopic metastases while RIT may exterminate this
      population of cells. Therefore, the combined treatment may improve the
      therapeutic outcome of patients with disseminated cancer.

PMID- 11585289
TI  - Routine ventilation scans in children with cystic fibrosis: diagnostic usefulness
      and prognostic value.
AB  - Krypton ventilation scans (VS) provide an index of peripheral lung function, and
      may be particularly useful in children unable to perform pulmonary function
      testing. This communication reports on three linked studies which investigated
      whether a routine VS in young children with cystic fibrosis (CF) is
      diagnostically or prognostically useful. Study 1: In a preliminary study in 1991,
      VS were compared with clinical examination and chest radiography (CXR) in 50 CF
      children (29 females, 21 males) aged 0.4-5.2 years (median 2.2 years). The chest
      was divided into six zones, and abnormalities scored from 0 (normal) to 2 (very
      abnormal). Clinical examination was unhelpful in predicting abnormalities on
      imaging. In five children (10%) with a normal CXR, VS was abnormal, and in a
      further eight children (16%), CXR markedly underestimated VS changes. Study 2: In
      order to determine the long-term prognostic significance of VS abnormalities, we
      followed up 27 (19 females, 8 males) of the children from study 1, who had had
      their first VS at presentation at median age 1.6 years (range 0.4-5.2), scoring
      the same six zones from 0 to 2. Follow-up was for a mean of 11.6 years (range 7.8
      14.8). Spirometry at age 7 years showed a mean forced expiratory volume in 1 s
      (FEV1) of 96% (range 46%-145%) and a mean forced vital capacity (FVC) of 96%
      (range 46%-145%). A poor VS score at presentation was correlated with percent
      predicted FEV1 at age 7 (r=0.4, P=0.042, 16% of variance explained). Those with a
      normal VS at presentation had a mean FEV1 at presentation of 99% (range 80%
      129%). Whereas four patients had an abnormal VS, a normal CXR and a low FEV1 at
      age 7 years, no patient had a normal VS, an abnormal CXR and a low FEV1 at age 7
      years. Study 3: Fifty children (29 females, 21 males) aged 0.5-6.0 years (median
      3.8) were prospectively studied in 1998, to determine whether the findings in
      study 1 were stable over time, and to assess whether VS altered clinical
      management. Symptoms and clinical examination did not predict abnormalities on
      imaging. Thirty (60%) children had a normal VS while only five (10%) had a normal
      CXR. There was a significant correlation between the total scores of CXR and VS
      (P=0.007, 14% of variance explained). Further, VS detected additional
      abnormalities in seven patients (14%). Sixty-five percent of patients with an
      abnormal VS had modifications of treatment, including bronchoscopy, compared with
      23% of those with a normal VS. We conclude that VS is a simple, safe and non
      invasive technique giving additional information to that provided by clinical
      examination and chest radiography in a number of children with CF and can be used
      to modify clinical management. VS at presentation gives prognostic information,
      which may be of use in early intervention studies. Whether using VS to guide
      treatment improves long-term prognosis requires a larger prospective trial.

PMID- 11585290
TI  - [177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients.
AB  - The somatostatin analogue [DOTA0,Tyr3]octreotate has a nine-fold higher affinity
      for the somatostatin receptor subtype 2 as compared with [DOTA0, Tyr3]octreotide.
      Also, labelled with the beta- and gamma-emitting radionuclide lutetium-177, this
      compound has been shown to have a very favourable impact on tumour regression and
      animal survival in a rat model. Because of these reported advantages over the
      analogues currently used for somatostatin receptor-mediated radiotherapy, we
      decided to compare [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) with [111In
      DTPA0]octreotide (111In-octreotide) in six patients with somatostatin receptor
      positive tumours. Plasma radioactivity after 177Lu-octreotate expressed as a
      percentage of the injected dose was comparable with that after 111In-octreotide.
      Urinary excretion of radioactivity was significantly lower than after 111In
      octreotide, averaging 64% after 24 h. The uptake after 24 h, expressed as a
      percentage of the injected dose of 177Lu-octreotate, was comparable to that after
      111In-octreotide for kidneys, spleen and liver, but was three- to fourfold higher
      for four of five tumours. The spleen and kidneys received the highest absorbed
      doses. The doses to the kidneys were reduced by a mean of 47% after co-infusion
      of amino acids. It is concluded that in comparison with the radionuclide-coupled
      somatostatin analogues that are currently available for somatostatin receptor
      mediated radiotherapy, 177Lu-octreotate potentially represents an important
      improvement. Higher absorbed doses can be achieved to most tumours, with about
      equal doses to potentially dose-limiting organs; furthermore, the lower tissue
      penetration range of 177Lu as compared with 90Y may be especially important for
      small tumours.

PMID- 11585291
TI  - Influence of OSEM and segmented attenuation correction in the calculation of
      standardised uptake values for [18F]FDG PET.
AB  - Standardised Uptake Values (SUVs) are widely used in positron emission tomography
      (PET) as a semi-quantitative index of fluorine-18 labelled fluorodeoxyglucose
      uptake. The objective of this study was to investigate any bias introduced in the
      calculation of SUVs as a result of employing ordered subsets-expectation
      maximisation (OSEM) image reconstruction and segmented attenuation correction
      (SAC). Variable emission and transmission time durations were investigated. Both
      a phantom and a clinical evaluation of the bias were carried out. The software
      implemented in the GE Advance PET scanner was used. Phantom studies simulating
      tumour imaging conditions were performed. Since a variable count rate may
      influence the results obtained using OSEM, similar acquisitions were performed at
      total count rates of 34 kcps and 12 kcps. Clinical data consisted of 100 patient
      studies. Emission datasets of 5 and 15 min duration were combined with 15-, 3-, 2
      and 1-min transmission datasets for the reconstruction of both phantom and
      patient studies. Two SUVs were estimated using the average (SUVavg) and the
      maximum (SUVmax) count density from regions of interest placed well inside
      structures of interest. The percentage bias of these SUVs compared with the
      values obtained using a reference image was calculated. The reference image was
      considered to be the one produced by filtered back-projection (FBP) image
      reconstruction with measured attenuation correction using the 15-min emission and
      transmission datasets for each phantom and patient study. A bias of 5%-20% was
      found for the SUVavg and SUVmax in the case of FBP with SAC using variable
      transmission times. In the case of OSEM with SAC, the bias increased to 10%-30%.
      An overall increase of 5%-10% was observed with the use of SUVmax. The 5-min
      emission dataset led to an increase in the bias of 25%-100%, with the larger
      increase recorded for the SUVmax. The results suggest that OSEM and SAC with 3
      and 2 min transmission may be reliably used to reduce the overall data
      acquisition time without compromising the accuracy of SUVs.

PMID- 11585292
TI  - FDG-PET as a "metabolic biopsy" tool in thoracic lesions with indeterminate
      biopsy.
AB  - A common problem encountered in clinical medicine is the classification of a lung
      lesion (nodule/opacity) on conventional imaging. Often attempts at biopsy are
      unsuccessful or are falsely reassuring, and the decision to send the patient for
      more invasive and potentially morbid procedures can be difficult. Our aim was to
      investigate the role of fluorine-18 fluorodeoxyglucose positron emission
      tomography (FDG-PET) in helping to identify more accurately those patients with
      malignant lesions. Sixty-three patients underwent FDG-PET scans following
      unsuccessful biopsy of a lung lesion or, in a lesser number of cases, when an
      attempt at biopsy was considered too dangerous. Follow-up was by histology or, if
      this was unavailable, by clinical progress to death or a minimum of 18 months
      post scan. Visual and quantitative analysis was performed. On visual analysis,
      positive and negative predictive values were 90% and 100%, respectively. On
      quantitative (SUV>2.5) analysis, positive and negative predictive values were 90%
      and 85%, respectively. We interpret these results as showing that the use of FDG
      PET scans in patients in this circumstance is non-invasive and highly sensitive
      in diagnosing malignancy. The high positive predictive value suggests that those
      with a positive scan must undergo further investigation, while the 100% negative
      predictive value means those with no FDG uptake can safely be spared further
      invasive investigations

PMID- 11585293
TI  - The role of 99mTc-MIBI scintigraphy in the assessment of MDR1 overexpression in
      patients with musculoskeletal sarcomas: comparison with therapy response.
AB  - The occurrence of multidrug resistance (MDR), which is in part due to the
      overexpression of P-glycoprotein (Pgp), is a major problem in neoadjuvant therapy
      of malignant musculoskeletal tumours. The aim of this study was to investigate
      the role of technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI)
      scintigraphy for functional imaging of the MDR1 phenotype in patients with
      musculoskeletal sarcomas. We aimed to compare 99mTc-MIBI uptake and washout
      kinetics with the expression of Pgp and with chemotherapy response. Twenty-five
      patients (16 males and 9 females, aged between 8 and 65 years) with malignant
      musculoskeletal tumours were studied. After injection of 555-740 MBq 99mTc-MIBI,
      dynamic flow images of the involved area were obtained for 3 min, and planar
      images were acquired at 10 min and 1 h. From the dynamic images, a tumour
      perfusion index (TPI) was obtained using Patlak-Rutland analysis. Tumour to
      background (T/B) ratios of both early and delayed images and percent wash-out
      rate (WR%) of 99mTc-MIBI were calculated. Immunohistochemical analysis of Pgp was
      performed on biopsy specimens and the degree of expression was graded according
      to a semiquantitative scoring system, from 0 to 6. After neoadjuvant therapy,
      tumour response was assessed by examining the ratio of viable cells and by
      detecting percent necrosis. Scintigraphic results were compared with Pgp status
      and therapy response. Irrespective of the Pgp status, all patients showed
      significant perfusion and 99mTc-MIBI uptake in early images. There was not a
      significant correlation between T/B ratios of early and delayed images and Pgp
      expression. We observed a positive correlation between WR% and Pgp status
      (r=0.61, P<0.01), and the wash-out rate of 99mTc-MIBI was significantly higher in
      patients with high Pgp expression than in those with a low Pgp score (33% +/- 9%
      vs 17% +/- 9%). Therapy response was determined in 21 of 25 patients, and in only
      5 of 21 cases was the percent necrosis more than 90%. Neither Pgp expression rate
      nor WR% was found to show a significant correlation with percent necrosis in the
      bulk tumour specimens. In conclusion, the initial uptake of 99mTc-MIBI in bone
      and soft tissue sarcomas did not correlate with Pgp expression. A relationship
      was found between the wash-out rate of 99mTc-MIBI and the Pgp score, with a
      significant difference in WR% being observed between patients with high and
      patients with low Pgp expression.

PMID- 11585294
TI  - Clinical role of 99mTcO4/MIBI scan, ultrasound and intra-operative gamma probe in
      the performance of unilateral and minimally invasive surgery in primary
      hyperparathyroidism.
AB  - The main purposes of this study were: (a) to investigate the efficacy of an
      imaging protocol based on the combination of 99mTcO4/MIBI scintigraphy and neck
      ultrasound (US) in selecting patients with primary hyperparathyroidism (HPT) for
      unilateral neck exploration, and (b) to help define the role of the
      intraoperative MIBI gamma probe (IMGP) technique in the performance of minimally
      invasive radio-guided surgery (MIRS). One hundred and forty-three consecutive
      patients with primary HPT were enrolled in the study. We used a modified
      99mTcO4/MIBI scintigraphic procedure which included the oral administration of
      potassium perchlorate to cause rapid 99mTcO4 washout from the thyroid tissue,
      thereby permitting the acquisition of high-quality early MIBI images. A single
      photon emission tomography (SPET) acquisition was also obtained in 21 patients,
      of whom seven had an enlarged parathyroid gland (EPG) in the mediastinum at
      planar scintigraphy and 14 had discordant scan/US findings for the presence of a
      cervical EPG. Neck US was performed in the same session as scintigraphy using a
      small-parts, high-resolution 10-MHz transducer. All patients were then operated
      on by the same surgical team. Quick PTH assay (QPTH) was used to measure PTH
      intraoperatively to confirm successful parathyroidectomy. In patients with
      scan/US evidence of a solitary EPG and with a normal thyroid gland, limited,
      unilateral neck surgery or, more recently, MIRS was planned (n=91). In patients
      with scan/US evidence of multiglandular disease (MGD) (n=21) or concomitant
      nodular goitre (n=24) or in patients with a negative scan/US evaluation (n=7),
      extensive bilateral neck exploration was planned (n=52). In 87 of the 91 patients
      (95.6%) in whom preoperative imaging indicated the presence of a solitary EPG and
      a normal thyroid gland, a single parathyroid adenoma was found at surgery, and
      these patients were treated by unilateral neck exploration or MIRS. In the
      remaining four patients of this group, conversion to bilateral neck exploration
      was required because parathyroid carcinoma (n=3) or MGD (n=1) was diagnosed at
      operation. In some cases SPET was helpful in better localising the EPG. In
      particular, in 5 of the 21 patients evaluated, SPET localised an EPG deep in the
      neck or mediastinum and at surgery a parathyroid adenoma was found in the
      paratracheal or para-oesophageal space. In 43 of the 46 patients (93.5%) who were
      candidates for MIRS, the IMGP technique allowed parathyroidectomy to be performed
      through a small, 2- to 2.5-cm skin incision with a short duration of intervention
      (mean 34 min). We conclude that: (a) The integrated scan/US imaging protocol that
      we used appears to be accurate in selecting patients with primary HPT for
      unilateral neck exploration. (b) In our series the most prevalent cause of
      bilateral neck exploration was the co-existence of a nodular goitre; thus
      accurate preoperative evaluation of the thyroid gland by dual-tracer scintigraphy
      and US imaging is strongly recommended in all patients with HPT. (c) SPET can
      provide the surgeon with useful information when an EPG is located deep in the
      neck or mediastinum. (d) IMGP appears to be a useful intraoperative device in HPT
      patients with solitary parathyroid adenomas and a normal thyroid gland, since it
      permits minimally invasive and time-saving surgery.

PMID- 11585295
TI  - Antithyroid drugs as a factor influencing the outcome of radioiodine therapy in
      Graves' disease and toxic nodular goitre?
AB  - There is controversy over the factors that may influence the outcome of
      radioiodine therapy for benign thyroid diseases. Antithyroid medication has been
      claimed to negatively influence the effectiveness of radioiodine therapy in
      Graves' disease. In a longitudinal study, we assessed the influence of sex, age,
      antithyroid drugs, target radiation dose, target mass, applied activity,
      delivered dose, interval between last meal and application, and TSH, FT3 and FT4
      levels on the outcome of radioiodine therapy. One hundred and forty-four patients
      (111 female, 33 male) suffering from Graves' disease (GD) and 563 patients (434
      female, 129 male) with toxic nodular goitre (TNG) were entered in the study and
      followed up until 8 months after therapy. Treatment was defined as successful
      when the TSH level was found to be normal or elevated. Ninety-eight GD patients
      and 418 TNG patients were successfully treated. Forward stepwise multiple
      regression analysis models retained only the target mass in GD and the applied
      activity in TNG as significantly associated with the outcome of therapy. The
      predictive value of all variables involved was extremely low in both disease
      groups. Whereas concomitant antithyroid medication had no influence in GD, it
      adversely influenced radioiodine therapy of TNG. This effect may be attributed to
      a radioiodine "steal phenomenon" induced by TSH-stimulated normal thyroid tissue,
      which causes overestimation of the uptake in toxic nodules.

PMID- 11585296
TI  - Aerosol deposition and clearance measurement: a novel technique using dynamic
      SPET.
AB  - Planar gamma camera scintigraphy is a well-established technique for
      characterising the deposition and clearance of radiolabelled aerosols. While
      single-photon emission tomography (SPET) can offer superior assessment of
      radioaerosol deposition and better differentiation between peripheral and central
      deposition, the long acquisition times of single-headed SPET have largely
      prevented its use for measuring clearance or deposition of fast-clearing
      radioaerosols. This study investigated the feasibility of fast dynamic SPET
      imaging (1 min/frame) using a three-headed gamma camera to assess the regional
      and total deposition and clearance of different radioaerosols over a period of 26
      min. Six subjects inhaled nebulised technetium-99m diethylene triamine penta
      acetic acid radiolabelled aerosols with small and large droplet sizes [mass
      median aerodynamic diameter (MMAD) 3.2 +/- 0.2 and 6.5 +/- 0.2 microm, span 1.8
      and 1.7, respectively] and in normal (0.9%) or hypertonic (7%) saline with
      controlled breathing on four separate occasions. The penetration indices (PIs)
      calculated from the SPET data for normal saline were 0.50 +/- 0.04 and 0.36 +/-
      0.02 for the small and large droplet sizes, respectively. Consistent with the
      hygroscopic growth of the hypertonic aerosols, the PIs for hypertonic saline were
      lower, at 0.43 +/- 0.02 and 0.34 +/- 0.02 for the small and large droplet sizes,
      respectively. PIs calculated from the planar data showed similar trends, but
      failed to detect the significant difference seen with SPET between small normal
      and small hypertonic saline radioaerosols. In conclusion, the feasibility of
      using fast dynamic SPET for imaging radioaerosol deposition and associated
      radiolabel clearance in the lung has been successfully demonstrated. The fast
      SPET was able to reveal important differences in aerosol deposition that were not
      detected by planar imaging.

PMID- 11585297
TI  - Biodistribution and dosimetry of 99mTc-BTAP-annexin-V in humans.
AB  - The purpose of this study was to determine the biodistribution and the associated
      radiation dose of technetium-99m 4,5-bis(thioacetamido)pentanoyl-annexin-V (99mTc
      Apomate), a tracer proposed for the study of apoptosis. Eight patients (including
      two females) with normal kidney and liver functions were included in the study.
      An activity of 580 +/- 90 MBq of 99mTc-Apomate was injected intravenously,
      immediately followed by a dynamic study of 30 frames of 1 min each. At about 1 h,
      4 h and 20 h p.i., whole-body scans were acquired. All activity distributions
      were measured using a dual-head gamma camera. Before injection of activity, a
      transmission scan with a cobalt-57 flood source had been performed to determine
      patient attenuation. Blood samples were taken every 10 min during the first hour
      after injection, and at about 4 and 20 h. Urine and faeces were collected during
      the first 20 h. Organ uptake was estimated after correction for body background
      activity, attenuation and scatter. Residence times were calculated from the
      dynamic and whole-body studies and used as input in the Mirdose 3.1 program to
      obtain organ doses and effective dose. It was found that radioactivity strongly
      accumulated in the kidneys and the liver [at 70 min p.i., 28% +/- 8% and 20% +/-
      4% of the injected dose (ID), respectively]. Uptake in the target tissues
      (lymphomas or heart) was negligible from a dosimetric point of view.
      Extrapolating data from the first 20 h, one finds that approximately 73% of the
      ID will be excreted in the urine, and 27% in the faeces. The biological half-life
      of the activity in the total body was 16 +/- 7 h. Some organ doses +/- standard
      deviation (SD) in microGy/MBq were: kidneys 63 +/- 22, urinary bladder 20 +/- 6,
      spleen 15 +/- 3, liver 13 +/- 3, upper large intestine 12 +/- 6, lower large
      intestine 8 +/- 4, testes 6 +/- 2 and red bone marrow 4 +/- 0.7. The effective
      dose was 7.6 +/- 0.5 microSv/MBq, corresponding to a total effective dose of 4.6
      +/- 0.3 mSv for a nominal injected activity of 600 MBq. In conclusion, 99mTc
      Apomate has a high uptake in the kidneys and liver--in fact a factor of 1.3-1.6
      higher than that found for the previously studied 99mTc-(n-1-imino-4
      mercaptobutyl)-annexin-V. The biological half-life is shorter, however, but still
      long compared with the physical half-life of 99mTc. The faster appearance of
      activity in the intestines may preclude imaging of apoptosis in the abdomen. The
      effective dose is within the lower range of values reported for typical 99mTc
      compounds.

PMID- 11585298
TI  - Gastric emptying after a new, more physiological anti-obesity operation: the
      Magenstrasse and Mill procedure.
AB  - The Magenstrasse and Mill (M&M) procedure for obesity is designed to preserve
      normal gastric emptying mechanisms. The hypothesis investigated in this study was
      that gastric emptying would be normal after the M&M gastroplasty. Gastric
      emptying studies were performed using both liquid and solid test meals, in ten
      morbidly obese patients (MO group) and in 13 patients after the M&M procedure (MM
      group). Seven people of normal weight served as controls and were matched for
      age, sex and height to the M&M and MO groups. Three years after the M&M
      procedure, mean (SD) weight loss was 42 (19) kg, with a mean loss of excess
      weight of 58% (20%). Gastric emptying half-times (t 1/2) are expressed in
      minutes, as median values (25th and 75th percentiles). The t 1/2 for solids was
      97 (85-110) min in the control group, 140 (86-220) min in the MO group and 79 (46
      150) min in the MM group. Median gastric emptying for solids was 0.7% (0.6%-0.8%)
      per minute in the control group, 0.5% (0.3%-0.8%) in the MO group and 0.9% (0.4%
      1.4%) in the M&M group. There were no statistically significant differences in
      the emptying times of the three groups. It is concluded that the M&M procedure
      achieves acceptable weight loss, while preserving gastric emptying mechanisms and
      thus minimising possible side-effects such as vomiting, dumping and diarrhoea,
      which are common complications of gastric bypass procedures.

PMID- 11585299
TI  - Imaging macrophages and the apoptosis of granulocytes in a rodent model of
      subacute and chronic abscesses with radiolabeled monocyte chemotactic peptide-1
      and annexin V.
AB  - Monocytes/macrophages (Mphis), the predominant cell types in subacute and chronic
      inflammation, are attracted to and activated by monocyte chemotactic peptide-1
      (MCP-1). Mphis promote the resolution of inflammation through the induction of
      apoptosis and phagocytosis of senescent (spent) and bystander (superfluous)
      granulocytes. We wished to determine whether MCP-1, which selectively binds to
      Mphis, could be used to image subacute and chronic inflammation. We also sought
      to image granulocyte apoptosis within these lesions with technetium-99m labeled
      annexin V, a marker of apoptotic cells. Sterile inflammation was induced in 45 12
      week-old male Sprague-Dawley rats by deep intramuscular injection of turpentine
      into the right thigh. Groups of four to six animals were then imaged 1 h after
      tail vein injection of 37-148 MBq (1-4 mCi) of 99mTc-labeled MCP-1 or annexin V 1
      14 days after turpentine treatment. Image analysis showed significantly greater
      activity of both MCP-1 and annexin V in inflamed thighs than in control thighs
      (165%-290% and 188%-313%, respectively; P<0.01) on days 1-5 after turpentine
      injection. Dual autoradiography in animals co-injected with iodine-125 labeled
      bovine serum albumin on days 1 and 4 showed specific location of MCP-1 to
      infiltrating Mphis while annexin V localized to focal zones of apoptosis within
      granulocytic infiltrates adjacent to abscess cavities. Scintillation well
      counting on day 5 demonstrated significantly higher (P<0.005) ratios of abscess
      to control thigh specific activities for MCP-1 (5.83+/-2.17) and annexin V (9.24
      +/- 2.8) as compared to 125I-labeled bovine serum albumin (3.11 +/- 0.65). No
      significant increases in uptake were noted at imaging or ex vivo analyses on days
      13 and 14, when lesions were predominately fibrotic. It is concluded that 99mTc
      labeled MCP-1 and 99mTc-labeled annexin V both localize in zones of subacute
      inflammation, reflecting the density of Mphis and the incidence of apoptotic
      granulocytes, respectively. These agents may be useful in the characterization of
      subacute inflammation.

PMID- 11585300
TI  - Localisation of motor areas in brain tumour patients: a comparison of
      preoperative [18F]FDG-PET and intraoperative cortical electrostimulation.
AB  - Assessment of the exact spatial relation between tumour and adjacent functionally
      relevant brain areas is a primary tool in the presurgical planning in brain
      tumour patients. The purpose of this study was to compare a preoperative fluorine
      18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) activation
      protocol in patients with tumours near the central area with the results of
      intraoperative direct cortical electrostimulation, and to determine whether non
      invasive preoperative PET imaging can provide results equivalent to those
      achieved with the invasive neurosurgical "gold standard". In this prospective
      study, we examined 20 patients with various tumours of the central area,
      performing two PET scans (each 30 min after i.v. injection of 134-341 MBq
      [18F]FDG) in each patient: (1) a resting baseline scan and (2) an activation scan
      using a standardised motor task (finger tapping, foot stretching). Following
      PET/MRI realignment and normalisation to the whole brain counts, parametric
      images of the activation versus the rest study were calculated and pixels above
      categorical threshold values were projected to the individual MRI for bimodal
      assessment of morphology and function (PET/MRI overlay). Intraoperative direct
      cortical electrostimulation was performed using a Viking IV probe (5 pulses, each
      of 100 micros) and documented using a dedicated neuro navigation system. Results
      were compared with the preoperative PET findings. PET revealed significant
      activation of the contralateral primary motor cortex in 95% (19/20) of the brain
      tumour patients (hand activation 13/13, foot activation 6/7), showing a mean
      increase in normalised [18F]FDG uptake of 20.5% +/- 5.2% (hand activation task)
      and 17.2% +/- 2.5% (foot activation task). Additionally detected activation of
      the ipsilateral primary motor cortex was interpreted as a metabolic indication
      for interhemispheric compensational processes. Evaluation of the PET findings by
      cortical stimulation yielded a 94% sensitivity and a 95% specificity for
      identification of motor-associated brain areas. In conclusion, the findings
      indicate that a relatively simple and clinically available [18F]FDG PET
      activation protocol enables a sufficiently precise assessment of the local
      relation between the intracranial tumour and the adjacent motor cortex areas and
      may facilitate the presurgical planning of tumour resection.

PMID- 11585301
TI  - The safety of dipyridamole in patients undergoing myocardial perfusion
      scintigraphy prior to lung volume reduction surgery.
AB  - Patients with end-stage chronic obstructive pulmonary disease (COPD) undergoing
      lung volume reduction surgery (LVRS) are at high risk of peri-operative cardiac
      complications, and myocardial perfusion scintigraphy (MPS) is commonly used for
      risk stratification. This study prospectively assessed the safety of dipyridamole
      in these patients and compared the incidence of side-effects (particularly
      dyspnoea) with that in patients undergoing dipyridamole MPS prior to elective non
      cardiothoracic surgery. Fifty patients were enrolled: 25 in the LVRS cohort (13
      males, 12 females), with a mean age of 65 years and a mean FEV1 of 0.791, and 25
      (with no history of asthma or COPD) in the control cohort (14 males, 11 females),
      with a mean age of 66 years. Fourteen patients (56%) in each group developed side
      effects. Dyspnoea was reported by five patients (20%) in the LVRS and two
      patients (8%) in the control cohort (P=NS). One patient in each cohort developed
      severe hypotension and bradycardia. Eight (32%) other patients developed minor
      side-effects in the LVRS cohort compared with 11 (44%) in the control group. All
      side-effects responded promptly to intravenous aminophylline. In summary, there
      was a statistically non-significant increase in the incidence of dyspnoea in
      patients with end-stage COPD and all side-effects responded to aminophylline.
      Thus, dipyridamole can be used safely in these patients.

PMID- 11585302
TI  - New trends in parathyroid scintigraphy.
AB  - The paper focusses on the recent advances in parathyroid imaging in both
      diagnostic and surgical fields which justify the present favourable trend towards
      a considerable expansion of nuclear medicine applications in this area. The main
      methodological advances in parathyroid scintigraphy are the rebirth of the dual
      tracer (subtraction) technique with technetium-99m sestamibi, the possibility of
      also using 99mTc-tetrofosmin within a dual-tracer (subtraction) methodology and
      the more extensive use of single-photon emission tomography, which the authors
      believe will become the standard methodology. The indications for parathyroid
      scintigraphy have been affected by advances in hyperparathyroidism surgery,
      including wider use of unilateral neck exploration and of minimally invasive
      radioguided surgery. As these techniques can only be performed in
      hyperparathyroid patients with a single adenoma, careful pre-operative assessment
      is required, and parathyroid scintigraphy undoubtedly is the most accurate
      localisation method. To date, the majority of papers have also demonstrated the
      cost-effectiveness of scintigraphically guided limited neck surgery. The authors
      conclude that: (1) parathyroid scintigraphy can be recommended not only in
      persistent or recurrent hyperparathyroidism but also in hyperparathyroid patients
      prior to first surgery; (2) scintigraphy should always be performed by applying
      the most accurate technique available because reliable scintigraphy gains or
      reinforces the surgeon's trust, reliably guides cost-effective operative
      strategies and justifies the recognition of new potential diagnostic indications.

PMID- 11585303
TI  - Somatostatin receptor-mediated imaging and therapy: basic science, current
      knowledge, limitations and future perspectives.
AB  - In vivo somatostatin receptor-mediated scintigraphy has proven to be a valuable
      method for the visualisation of neuroendocrine tumours and their metastases. A
      new application is the use of radiolabelled analogues for somatostatin receptor
      mediated therapy. This paper presents a review on the basic science, historical
      background and current knowledge of somatostatin receptor subtypes and their
      expression in neuroendocrine tumours. New somatostatin analogues, new chelators,
      "new" radionuclides and combinations thereof are also discussed. Due attention is
      given to limitations and future perspectives of somatostatin receptor-mediated
      imaging and therapy.

PMID- 11585304
TI  - Bone marrow uptake of 99mTc-MIBI in patients with multiple myeloma.

PMID- 11585305
TI  - Direct infiltration of therapeutic radiopharmaceuticals into tumors.

PMID- 11585306
TI  - Higher relative biological efficiency of alpha-particles: in vitro veritas, in
      vitro vanitas?

PMID- 11585307
TI  - Two years' experience using no-carrier-added meta-[123I]iodobenzylguanidine in
      clinical studies.

PMID- 11585308
TI  - Impact of patient positioning in scintimammography.

PMID- 11585309
TI  - Perfusion of the optic nerve head and visual field damage in glaucomatous
      patients.
AB  - PURPOSE: To examine the relation between perfusion of the optic nerve head and
      visual field defects in glaucomatous patients. METHODS: A study was performed on
      94 patients affected with primary open-angle glaucoma. The optic nerve head blood
      flow was measured by means of a scanning laser Doppler flowmeter (Heidelberg
      Retina Flowmeter). Blood volume, flow and velocity were analysed in two areas of
      the rim and in one area of the lamina cribrosa. The visual field was tested with
      the 30-2 full threshold white-on-white program and mean deviation (MD) and
      corrected pattern standard deviation (CPSD) were considered as parameters of
      visual field defects. RESULTS: The interindividual analysis showed that the
      vascular parameters of the neuroretinal rim circulation were not significantly
      correlated with visual field parameters. The blood volume, flow and velocity of
      lamina cribrosa correlated significantly with both MD (R=0.519, R=0.549 and
      R=0.531, respectively; P<0.001) and CPSD (R=-0.496, R=-0.363 and R=-0.363,
      respectively; P<0.001). The intraindividual correlations (right-left differences
      of parameters) showed that the side differences of MD and CPSD correlated
      significantly with the side differences of blood volume (R=0.511 and R=-0.477,
      respectively), flow (R=0.554 and R=-0.390, respectively) and velocity (R=0.541
      and R=-0.372, respectively) in lamina cribrosa. CONCLUSION: These findings
      suggest that in glaucoma patients the perfusion parameters of lamina cribrosa are
      significantly correlated with visual field defects.

PMID- 11585310
TI  - Comparison of different high resolution multifocal electroretinogram recordings
      in patients with age-related maculopathy.
AB  - AIM: to compare two different resolutions of multifocal electroretinogram
      recordings (MF-ERG) in patients with age-related macular degeneration (AMD).
      PATIENTS AND METHODS: in 20 eyes (14 patients) with early or late stages of AMD,
      MF-ERGs of 8 min duration were recorded using a low and a high resolution. The
      central 50 degrees of the retina were stimulated by 103 as well as by 241
      stimulus elements. Results were compared with one another and with an age-matched
      control group. RESULTS: when response averages of equal eccentricity were
      analysed, amplitudes of the MF-ERG differed significantly from normal within the
      central 40 degrees. This held true for both low (103) and high (241) resolutions.
      Sixteen of 20 eyes also showed focal retinal dysfunction at both resolutions. In
      one case, the high resolution MF-ERGs could detect functional deficits that could
      not be seen with the lower resolution. However, due to a reduced signal-to-noise
      ratio three high resolution recordings could not be analysed. CONCLUSION: high
      resolution MF-ERG seems more sensitive than low resolution MF-ERG. However, the
      low resolution (103) MF-ERG is recommended for routine application in the clinic
      because of its better signal-to-noise ratio.

PMID- 11585311
TI  - The Freiburg Stereoacuity Test: automatic measurement of stereo threshold.
AB  - BACKGROUND: There is a need for a stereotest with the following properties: (1)
      Natural viewing conditions, i.e. stimulus contours visible for each eye alone,
      but no or hardly any cue for monocular detection, and (2) suitability for
      threshold determination over a wide range of disparities. To comply with these
      requirements, we developed the Freiburg Stereoacuity Test. METHOD: The stimulus
      configuration is shown on a visual display unit (VDU) using phase-difference
      haploscopy with ferromagnetic liquid crystal shutters. The stereo target consists
      of a vertical bar that can be presented "in front of' or "behind" a frame. The
      sizes of the bar and the frame are kept constant relative to the stereo
      disparity. Anti-aliasing allows for disparities finer than the pixel raster. To
      mask monocular cues the bar is displaced randomly to the right or left. The
      stereo threshold was determined in two observers with normal eyes, using first
      the method of constant stimuli and then the best PEST. Both procedures were
      repeated with observers wearing scatter transparencies that reduced their visual
      acuity to about 1/10. In addition, the two observers with insight into the test
      design and two strabismic patients performed the best PEST procedure with one eye
      only. RESULTS: With constant stimuli both observers achieved a stereoacuity of
      2.6 arcsec and 3.1 arcsec, respectively, taking a hit rate of 75% as the
      threshold. The best PEST revealed a stereoacuity of 2.5 arcsec and 3.0 arcsec,
      respectively. The scatter transparencies raised the threshold to 261 and 257,
      respectively. With one eye only, the two observers with insight into the test
      design exploited the subtle position cue and reached a coarse pseudostereopsis.
      The two strabismic patients did not utilise the position cue. CONCLUSION: The
      Freiburg Stereoacuity Test allows determination of stereoacuity over a wide range
      of disparities (1-1000 arcsec). Although the stimuli can be seen with each eye
      alone, monocular depth cues are sufficiently masked. The Freiburg Stereoacuity
      Test is available at http://www.ukl.uni-freiburg.de/aug/bach/fst/.

PMID- 11585312
TI  - Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment
      (SPR Study): design issues and implications. SPR Study report no. 1.
AB  - BACKGROUND: In patients with more complex rhegmatogenous retinal detachments
      (RRD) not complicated by proliferative vitreoretinopathy (PVR), the most
      appropriate operating method is controversial, and different surgeons use
      different techniques. The Scleral Buckling Versus Primary Vitrectomy in
      Rhegmatogenous Retinal Detachments Study (SPR Study) is designed to compare
      primary vitrectomy and scleral buckling techniques in these patients. METHODS:
      The SPR Study is a multicentre, randomised, controlled clinical trial stratified
      by lens status. Patients with RRD which is not complicated by PVR grade B or C
      and which cannot be treated with a single meridional sponge are randomised to
      either scleral buckling or pars plana vitrectomy as first surgical intervention.
      Four hundred consecutive patients are to be recruited per subtrial (phakic and
      aphakic/pseudophakic patients), and followed up for 1 year. The primary endpoint
      (functional outcome) is the change in visual acuity. Secondary endpoints
      (anatomical outcome) include postoperative PVR, retinal reattachment and the
      number of reoperations necessary to achieve retinal reattachment. Twenty-seven
      institutions (49 surgeons) in six European countries have been recruited for
      participation in the study. CONCLUSION: The SPR Study is the first randomised
      prospective clinical trial to compare scleral buckling and primary vitrectomy in
      patients with RRD. The results of this study should enable vitreoretinal surgeons
      to improve the surgical therapy of patients with the more complicated
      manifestations of RRD.

PMID- 11585313
TI  - Clinical and electrophysiological findings in autosomal dominant
      vitreoretinochoroidopathy: report of a new pedigree.
AB  - PURPOSE: To report the clinical and electrophysiological findings in a three
      generation pedigree with autosomal dominant vitreoretinochoroidopathy. METHODS:
      Sixteen members of a three-generation pedigree with autosomal dominant
      vitreoretinochoroidopathy were examined clinically, including measurement of the
      corneal diameter. In 14 persons, Goldmann perimetry, axial length determination
      and electro-oculography were carried out. Electroretinography, according to ISCEV
      standards, was performed in 11 of 12 affected persons. RESULTS: Characteristic
      annular peripheral pigmentary changes were present in all affected members, as
      well as chorioretinal atrophy varying from a tigroid aspect to marked atrophy.
      Four patients presented a microcornea and shallow anterior chamber without
      microphthalmia. The visual fields appeared to narrow with ageing. The electro
      oculography was pathological in the affected patients and normal in the
      unaffected. The electroretinographic amplitude responses tended to worsen with
      age, with maintenance of near normal latencies. CONCLUSION: The clinical
      presentation of autosomal dominant vitreoretinopathy is variable.
      Electrooculography seems to be a discriminative test. The condition may be
      associated with anterior segment abnormalities other than presenile cataract,
      such as microcornea, shallow anterior chamber and angle closure glaucoma.

PMID- 11585314
TI  - Transvenous embolization of carotid cavernous fistulas via the superior
      ophthalmic vein.
AB  - BACKGROUND: Treatment of choice for symptomatic carotid-cavernous and cavernous
      dural fistulas is neuroradiologic intervention via the femoral artery. Owing to
      the location of the fistula and/or to anatomic variations, a direct surgical
      approach via the superior ophthalmic vein may be necessary for embolization.
      METHODS: Three patients presented with exophthalmos, episcleral venous
      congestion, chemosis, restricted eye movement, and secondary glaucoma. One
      patient had visual impairment and scotoma due to compression of the optic nerve
      by the fistula. The tentative diagnosis of an arteriovenous fistula was confirmed
      in two cases by color Doppler imaging and in all three cases with cerebral
      arterial angiography (two carotid-cavernous fistulas, one cavernous-dural
      fistula). After an unsuccessful transarterial attempt, embolization via the
      superior ophthalmic vein was chosen. RESULTS: In all three patients the
      preparation of the superior ophthalmic vein was performed without any
      complications. In two cases the fistula could be embolized completely with
      platinum coils. In one patient the placement of the microcatheter was impossible,
      because of an abnormal vascular pattern. Later on the fistula was successfully
      embolized by an approach via the femoral vein. All three patients had complete
      resolution of symptoms. There were no recurrences. CONCLUSION: Embolization of
      carotid-cavernous and cavernous-dural fistulas by a surgical approach via the
      superior ophthalmic vein represents safe and effective treatment when standard
      transarterial access is impossible. The cooperation of an orbital surgeon and an
      invasive neuroradiologist can be of benefit for this rare group of patients.

PMID- 11585315
TI  - Pseudophakic correction factors for optical biometry.
AB  - INTRODUCTION: The IOLMaster of Carl Zeiss Jena, which has recently become
      available, is a combined instrument for biometry and intraocular lens (IOL)
      planning for cataract surgery utilizing partial coherence interferometry for
      measuring axial length. Whereas measurement data from classical ultrasound
      biometry, e.g. in pseudophakic eyes, need to be corrected by +0.4 to -0.8 mm-
      depending on the lens material--smaller corrections are expected to be necessary
      in optical biometry. Correction factors for various modern IOL materials were
      estimated theoretically and checked in first clinical measurements. METHODS:
      Starting from the dispersion relation of PMMA and manufacturers' phase refractive
      index data at 546 nm, the group refractive indices of different IOL materials
      were estimated for the IOLMaster wavelength of lambda=780 nm. Then, for an
      average eye of 23.48 mm, the center thicknesses of emmetropizing lenses of
      different material were calculated. Finally, comparing the pseudophakic optical
      axial lengths thus deduced with the respective phakic value, individual material
      specific correction factors were obtained. RESULTS: Expressing the true axial
      length ALtrue by the length ALphak measured in phakic mode and a correction
      factor delta (ALtrue=Alphak+delta), we obtained values of delta=0.12+/-0.01 mm
      for all IOL materials considered (PMMA, silicone, collamer, AcrySof, MemoryLens).
      For aphakic eyes, delta=0.20 mm was deduced. DISCUSSION: The calculations
      suffered from the fact that hardly any information relating to optical material
      specifications of IOLs is available from lens manufacturers. Therefore,
      calculations had to be based on--nevertheless realistic--assumptions. Early
      clinical results support our theoretical findings. Thus, optical biometry seems
      to be more reliable and forgiving in pseudophakic eyes than classical ultrasound.

PMID- 11585316
TI  - Changes in ocular blood flow velocities during external counterpulsation in
      healthy volunteers and patients with atherosclerosis.
AB  - BACKGROUND: External counterpulsation (ECP) is a new noninvasive means of
      augmenting organ perfusion by applying ECG-triggered diastolic pressure to the
      vascular bed of the lower limbs. In this study, effects of ECP on changes of
      ocular blood flow velocities were studied. METHOD: Mean, systolic and diastolic
      flow velocities of the ophthalmic artery were measured by Doppler sonography
      before and during ECP. Twelve healthy volunteers (age 31.3+/-4.3 years) and 12
      patients with severe atherosclerosis (inclusion criteria: two atherosclerotic
      risk factors, at least one severe coronary stenosis, age 62.1+/-5.3 years) were
      included in the study. RESULTS: In healthy subjects, ECP changed diastolic flow
      velocity of the ophthalmic artery nonsignificantly from 21.6+/-7.7 to 23.7+/-10.5
      cm/s. Systolic flow velocity decreased significantly from 36.1+/-13.6 to 28.9+/
      10.2 cm/s (P<0.01). Mean flow velocity changed nonsignificantly from 28.1+/-9.4
      to 26.5+/-9.9 cm/s. In atherosclerotic patients, mean flow velocity increased
      significantly from 26.3+/-11.4 to 29.3+/-11.2 cm/s (P<0.001), which was caused by
      significant diastolic flow augmentation from 19.7+/-9.1 to 23.9+/-9.7 cm/s
      (P<0.001). Systolic flow velocity was not changed significantly (from 34.2+/-12.8
      to 32.6+/-11.8 cm/s). CONCLUSION: No significant change of mean blood flow
      velocity in the ophthalmic artery was found in young healthy subjects. In elderly
      patients with atherosclerosis, ECP significantly increased blood flow velocity in
      the ophthalmic artery by 11.4%. This may indicate an ocular perfusion benefit in
      these patients as a result of ECP and could also explain the increase of
      perfusion found in patients with retinal ischemia after ECP.

PMID- 11585317
TI  - Short-term visual rehabilitation after LASIK.
AB  - PURPOSE: To determine the early course of visual recovery after LASIK for myopia.
      METHODS: In eight eyes visual acuity, both uncorrected and corrected, objective
      refraction, topography and contrast sensitivity were measured six times during
      the first day, twice daily for two days and after 1 week. RESULTS: Patients
      experienced considerable variability in achieving best corrected visual acuity.
      80% of patients already had uncorrected visual acuity of 0.5 or better 1 day
      after surgery. By the 16th hour 97% of preoperative best spectacle-corrected
      visual acuity was achieved. The mean radius of anterior corneal curvature was
      already relatively constant after 3 h. After that the corneal topography was
      fairly stable. CONCLUSIONS: Vision recovers rapidly after LASIK. Visual
      rehabilitation was reached after 16 h in most cases. Mesopic vision, however, was
      reduced after LASIK.

PMID- 11585318
TI  - Intraocular in vivo imaging of activated T-lymphocytes expressing green
      fluorescent protein after stimulation with endotoxin.
AB  - BACKGROUND: Intravital microscopy allows imaging of specific cell populations in
      vivo. The value of this technique is well established, but would be enhanced if
      one could distinguish functional states of cells in vivo. Interleukin-2 (IL-2) is
      expressed upon stimulation of T-cells and is a commonly used marker for T-cell
      activation. This study tests the use of enhanced green fluorescent protein (GFP)
      as a reporter gene for interleukin-2 (IL-2) expression in vivo. METHODS:
      Characterization of mice that have the GFP gene under the control of IL-2
      regulatory sequences has previously been published. Uveitis was induced by
      injection of E. coli endotoxin into the vitreous of these IL-2/GFPki transgenic
      mice. Four hours later, 3 microg of recombinant mouse IL-2 was injected into the
      anterior chambers of one group of mice. In vivo imaging of infiltrating cells in
      the iris stroma was performed with fluorescence microscopy at 6, 24, 48, and 72 h
      after endotoxin injection. The absolute number of fluorescent cells per mm2 was
      evaluated. RESULTS: Eyes with endotoxin-induced uveitis had cells that expressed
      GFP and were identifiable by intravital microscopy. The fluorescent cells were
      exclusively seen in the subset of cells that had infiltrated the iris stroma or
      arrested along the vascular endothelium. The number of GFP-positive infiltrating
      cells in the iris increased from undetectable at baseline to 0.5 cells/mm2 at 6 h
      and 1.3 cells/mm2 at 72 h. The animals that received endotoxin as well as IL-2
      tended to have more GFP-positive cells at the 48-h and 72-h time points, but
      these differences were not statistically significant CONCLUSIONS: GFP is commonly
      used as a reporter gene for in vitro expression assays. The results presented
      here document that transgenic mice with GFP under the control of IL-2 regulatory
      elements can be used with intravital microscopy for in vivo expression assays
      that allow detection of activated T-cells at multiple time points within the same
      animal. This provides a novel method for temporal and spatial studies on the
      state of cell activation in inflammatory responses.

PMID- 11585319
TI  - Specific features of apoptosis in human lens epithelial cells induced by
      mitomycin C in vitro.
AB  - BACKGROUND: Posterior capsule opacification (PCO) is still one of the major
      complications following modern cataract surgery. Several attempts have been made
      to find an appropriate therapeutic concept to significantly lower the rate of
      PCO. Here, we wanted to focus on the antimetabolic strategy, reducing PCO by
      using mitomycin C, further characterizing the pathway of apoptosis in human lens
      epithelial cells (hLECs). METHODS: Human lens epithelial cells were obtained from
      anterior lens capsules during cataract surgery. The expression of Fas, TRAMP,
      TRAIL-R1-R4, Apo-3L and TRAIL mRNA was investigated by means of RT-PCR using
      specific primers. For investigations on bcl-2, bax, p53 and the active form of
      caspase 3, cell cultures of hLECs were pretreated with mitomycin C and processed
      for immunocytochemistry thereafter. RESULTS: We detected the expression of the
      receptors Fas, TRAMP, TRAIL-R2 and TRAIL-R3 in hLECs. We further obtained
      evidence of the upregulation of the intracellular apoptotic signalling cascade,
      represented by bcl-2 and bax, the transcription factor p53 and the active form of
      caspase 3, after pretreatment with mitomycin C. CONCLUSION: We demonstrated the
      presence of the apoptosis-receptor system in hLECs. Furthermore, we demonstrated
      the possibility of the induction of key proteins of the apoptotic signalling
      cascade in these cells by the antimetabolic drug mitomycin C. This could have
      important implications on the strategies regarding both the prevention and the
      treatment of PCO after cataract surgery.

PMID- 11585320
TI  - Hepatocyte growth factor promotes epithelial morphogenesis and occludin linkage
      to the cytoskeleton in cultured retinal pigment epithelial cells.
AB  - BACKGROUND: Although hepatocyte growth factor (HGF) is also known as scatter
      factor, it induces epithelial morphogenesis in cultured bovine retinal pigment
      epithelial (RPE) cells. To elucidate the mechanism of epithelial morphogenesis,
      we investigated the influence of HGF on occludin, a major component of tight
      junctions. METHODS: RPE cells were plated on collagen type 1-coated chamber
      slides or dishes, 20 ng/ml HGF was added and the cells were incubated for 1 week.
      Cells were harvested at several time-points, and occludin expression was examined
      by immunohistochemistry. Detergent extraction protocols to identify the intensity
      of occludin linkage to the cytoskeleton were also used. Occludin expression was
      determined semiquantitatively by Western blotting. RESULTS: Fluorescence
      microscopy revealed that HGF treatment increased the levels of insoluble occludin
      at the cell borders after detergent extraction. These level of insoluble occludin
      and the associated epithelial morphology were maintained for more than 3 weeks
      after withdrawal of HGF, whereas cells not treated with HGF had a fibroblastic
      appearance. Western blotting also showed that insoluble occludin was more
      abundant in HGF-treated cells. Furthermore, immunoreactive bands of insoluble
      occludin were somewhat larger than those of soluble occludin, suggesting that
      insoluble occludin may be modified in comparison to soluble occludin. CONCLUSION:
      Our results suggest that HGF promotes linkage of occludin to the cytoskeleton.
      HGF may become a therapeutic candidate in physiological recovery of RPE cells and
      in preparation of RPE monolayers for transplantation.

PMID- 11585321
TI  - Orbital lymphangioma with positive immunohistochemistry of lymphatic endothelial
      markers (vascular endothelial growth factor receptor 3 and podoplanin).
AB  - BACKGROUND: Existence of true orbital lymphangiomas has been questioned in recent
      years. Therefore an orbital lymphangioma was analyzed with two new specific
      markers of lymphatic endothelium. METHODS: Case-report with clinicopathological,
      immunohistochemical, and ultrastructural findings. A 25-year-old man presented
      with recurrent lower lid "hematomas" and a pea-sized tumor palpable in the left
      lower lid. Magnetic resonance imaging showed an inferonasally located orbital
      tumor which extended to the posterior pole of the eye. The highly vascularized
      tumor was excised by medial orbitotomy. RESULTS: Histopathologically, the mass
      consisted of large, erythrocyte-filled cavernous vessels without evidence of
      smooth muscle cells or pericytes surrounding them. Numerous lymph follicles and
      small arterioles were scattered between them. Immunohistochemically, endothelial
      cells lining the lumina of the cavernous vessels were partly positive for
      podoplanin and vascular endothelial growth factor receptor 3 (flt-4), two markers
      of lymphatic endothelium. These markers did not react with endothelial cells
      lining the arterioles. Ultrastructurally, cavernous vessels displayed features
      characteristic of lymphatic vessels, and the smaller vessels demonstrated signs
      of arterioles. CONCLUSION: Ultrastructural analysis and immunohistochemistry
      using two new markers of lymphatic endothelium suggest a lymphatic nature of
      large vessels in an orbital lymphangioma. A greater series of vascular orbital
      tumors must be studied with these new lymph endothelial markers to confirm the
      existence of true orbital lymphangiomas and to analyze different profiles of
      lymph endothelial marker expression.

PMID- 11585322
TI  - Epidemiology of central nervous system tumors in childhood and adolescence based
      on the new WHO classification.
AB  - METHOD: The topography, sex distribution and histology of 340 primary CNS tumors
      in children up to 17 years of age were investigated and (re-)classified according
      to the latest WHO classification of nervous system tumors. RESULTS: Overall the
      prevalence for boys (60.9%) was higher and supratentorial locations predominated
      (53.3%); there was an even distribution of low-grade WHO I/II (51.5%) and high
      grade WHO III/IV (48.5%) tumors. Boys were more commonly affected in all age
      groups throughout childhood and adolescence. Infratentorial location was more
      common between the ages of 3 and 11 years (57.5%). High-grade tumors were more
      frequently encountered up to the age of 5 years (53.2%). The main histological
      entities were pilocytic astrocytomas (23.5%), followed by medulloblastomas
      (16.3%), ependymomas (10.1%), anaplastic astrocytomas and glioblastomas (7.2%
      each), and craniopharyngiomas (5.6%); astrocytomas overall accounted for 47.3% of
      pediatric brain tumors. Rarer entities included germ cell tumors, gangliogliomas,
      and meningiomas (2.5% each), supratentorial PNET and pineal parenchymal tumors
      (1.9% each), atypical teratoid/rhabdoid tumors (1.3%), choroid plexus tumors
      (0.9%), and desmoplastic infantile astrocytomas and dysembryoplastic
      neuroepithelial tumors (0.6% each). A meta-analysis of 10,582 childhood brain
      tumors accumulated from 16 international surveys revealed a male-female ratio of
      1.29 and a supra-/infratentorial ratio of 0.92. The most common histological
      diagnoses were astrocytomas (37.6%), medulloblastomas (17.7%), ependymomas
      (9.9%), craniopharyngiomas (7.3%), and germ cell tumors (4.4%). CONCLUSIONS:
      Pediatric brain tumors vary considerably in their histological, topographical and
      gender distribution throughout childhood and adolescence, reflecting different
      dynamics of individual tumor entities as well as a susceptibility to their
      occurrence during certain periods of a child's life. Although at times difficult
      to characterize, pediatric CNS tumors can be satisfactorily classified according
      to the latest WHO classification of nervous system tumors.

PMID- 11585323
TI  - A comparative MR and pathological study on fetal CNS disorders.
AB  - OBJECT: We used MR after sonography to help us in prenatal counseling in 58
      complicated pregnancies from 1998 to 2000. METHODS: All fetal MR examinations
      were undertaken with a 1.5-T magnet using a body-phased-array coil and an
      ultrafast imaging technique, half-Fourier single-shot turbo spin-echo (HASTE).
      Twelve fetuses were found to have major anomalies, and in each of these cases
      either delivery was induced or the pregnancy was terminated. In 6 of the fetuses,
      with anomalies of the central nervous system, postmortem examinations were then
      performed after they failed to survive, and these constitute the patient sample
      investigated in the current study. The fetal gestational ages in these 6 cases
      ranged from 24 to 32 weeks. MR imaging demonstrated morphological details of the
      anomalies. They were: alobar holoprosencephaly in 2, middle interhemispheric
      fusion in 1, alobar holoprosencephaly with Dandy-Walker malformations in 1, a
      Dandy-Walker variant in 1 and twin-twin transfusion syndrome with hypoxic
      ischemic injury to the brain in 1. CONCLUSIONS: Postmortem examinations confirmed
      the MR diagnoses, and these observations support us in improving our
      understanding of the pathogenesis of fetal CNS anomalies.

PMID- 11585324
TI  - Perfusion brain scintigraphy studies in infants and children with malformations
      of the vein of Galen.
AB  - Cerebral perfusion brain scintigraphy obtained in six unselected patients (age
      newborn to 14 years) from among 50 children with vein of Galen malformations was
      used in conjunction with magnetic resonance imaging to determine the basis of the
      neurological and cognitive abnormalities in patients with vein of Galen
      malformations (VGMs). Five had a hemiparesis - persistent, transient, or
      alternating. Four were developmentally delayed. Two had so far been cognitively
      normal and acquired a neurological deficit, following an embolization procedure.
      The school age patient had a nonverbal learning disability. Three had epilepsy
      and/or an abnormal electroencephalogram. Magnetic resonance imaging documented
      only the VGM, hydrocephalus and atrophy; one child with perinatal asphyxia had
      periventricular leukomalacia. Perfusion brain scintigraphy was normal in two (a
      normal infant, and a toddler with a hemiparesis and aphasia). Abnormal findings
      included: left parietal hypoperfusion, fronto-temporal atrophy, patchy flow; left
      fronto-temporal hypoperfusion, left hemiatrophy, bilateral medial temporal
      hypoperfusion, right cerebellar hypoperfusion; right temporal hypoperfusion,
      patchy flow; right hemiatrophy, occipital hypoperfusion. Perfusion brain
      scintigraphy findings correlated better with focal neurological and cognitive
      defects than did magnetic resonance imaging.

PMID- 11585325
TI  - Cranial infantile myofibromatosis: report of three cases.
AB  - BACKGROUND: Infantile myofibromatosis is a proliferative disorder of infancy and
      early childhood characterized by the development of single or multiple nodular
      lesions arising from cutaneous or subcutaneous tissue, muscle, bone or visceral
      organs. In approximately one-third of cases, this myofibroblastic proliferation
      involves the head and neck region. CASE REPORT: In this paper we report on three
      cases of cranial infantile myofibromatosis in infants. The clinical presentation
      and the deceptive histopathological features can make diagnosis difficult.
      CONCLUSION: The significance of recognizing this entity is stressed, since its
      indolent clinical behavior might prevent diagnosis.

PMID- 11585326
TI  - Split cord malformation: three unusual cases of composite split cord
      malformation.
AB  - BACKGROUND: All split cord malformations (SCMs) arise from one basic fault, i.e.
      the formation of an accessory neurenteric canal between yolk sac and amnion
      through the midline embryonic disc that splits the notochord and neural plate.
      Multiple accessory neurenteric canals may lead to two or more noncontiguous SCMs,
      also known as composite SCM. CASE HISTORIES: We present here three cases of
      composite SCM. First, a 2 1/2-year-old boy had type II SCMs at two different
      levels with normal cord between them. In case 2, a 16-month-old girl revealed a
      type I SCM at levels L2-3 and a type II SCM at level L5. The third case had a
      combination of both these types of SCMs at levels L1-3. Only very few cases of
      composite SCM have been reported in the literature. CONCLUSIONS: These three
      cases also support the unified theory proposed by Pang et al.

PMID- 11585327
TI  - Radical excision of pediatric craniopharyngioma: recurrence pattern and
      prognostic factors.
AB  - The purpose of our study was to investigate the pattern of recurrence and the
      prognostic factors for recurrence of pediatric craniopharyngiomas after radical
      excision. A series of 36 patients with craniopharyngiomas (21 boys and 15 girls;
      age range 1-15 years; mean 7.3 years) were reviewed. All patients had undergone
      radical excision without radiotherapy. The mean follow-up period was 52 months
      (range 1-149 months). Tumors recurred in 14 patients within 83 months (mean 31.4
      months). The overall 5-year recurrence-free survival rate was 55%. Regular
      neuroimaging follow-up detected tumor recurrence while the lesions were still
      small before symptoms developed (P<0.05). At the first surgical procedure, the
      optic nerve/chiasm (n=23) was the most common adhesion site. The most frequent
      sites of recurrence were the optic nerve/chiasm (n=6) and the pituitary fossa
      (n=6). Tumor location was the single significant clinical predictor of
      recurrence. The 5-year recurrence-free survival rate was 39% for those who had an
      intrasellar tumor component and 81% for those who did not (P<0.05). The Ki-67
      labeling indices (LIs) of primary tumors did not have prognostic value for
      recurrence. Recurrent tumors tended to have higher Ki-67 LIs than their primary
      counterparts. On the basis of this study, we concluded that craniopharyngiomas
      with intrasellar components should be followed cautiously and the necessity for
      regular follow-up should be emphasized, even when the tumor is "totally"
      resected.

PMID- 11585328
TI  - Uncommon presentation of medulloblastoma.
AB  - INTRODUCTION: Medulloblastoma commonly occurs in children as a midline posterior
      fossa mass arising from the vermis, which appears as a hyperdense, homogeneously
      enhancing mass on CT scan and is associated with the clinical profile of
      posterior fossa syndrome. This unique clinico-radiological pattern is considered
      'typical', but then medulloblastomas do not follow the typical clinico
      radiological pattern in a significant number of cases. PATIENTS: Out of the 42
      cases of medulloblastoma operated on at SGPGIMS from 1988 to 1998, 29 cases were
      retrospectively and 13 cases were prospectively studied to detect the atypical
      clinico-radiological features. The typical radiological feature of a hyperdense
      homogeneously enhancing mass was seen in only 23 of the 42 patients, while 5
      patients had hypodense nonenhancing masses, 13 had cystic changes, and 6 patients
      had calcifications in their tumours. Three patients presented with tumours in a
      very unusual location, i.e. the cerebellopontine angle cistern. RESULTS: During
      follow-up, which ranged from a minimum period of 1 year to a maximum of 9 years,
      patients came back with metastases at very unusual sites. There were 5 cases of
      metastases in the frontal and subfrontal area (developed between 5 months and 5
      years following surgery), and 1 patient developed a cervical intramedullary
      metastasis. Two patients developed abdominal metastases and ascites 2 years after
      definitive surgery and ventriculo-peritoneal shunting. Each of these 2 patients,
      however, had received a full course of craniospinal irradiation following
      surgery. Thus, we had a number of cases with an unusual clinical, radiological
      and metastatic pattern.

PMID- 11585329
TI  - Evaluation of the Cerebral Function Monitor as a tool for neurophysiological
      surveillance in neonatal intensive care patients.
AB  - BACKGROUND: Cerebral function in critically ill infants is difficult to assess
      and would certainly require continuous monitoring. Therefore, this study was
      performed to evaluate the Cerebral Function Monitor (CFM) as a tool for
      continuous neurophysiological surveillance in the Neonatal Intensive Care Unit
      (NICU). PATIENTS: A total of 40 neurological risk neonates were included in the
      study. They were classified on the basis of their primary diagnoses as infants
      with clinically manifest seizures, suspected seizure activity, intracranial
      hemorrhage (ICH) and hypoxic-ischemic encephalopathy (HIE). A group of 20
      neurologically normal (preterm and full-term) infants served as controls. RESULTS
      AND CONCLUSION: All patients with seizures showed pathologic patterns in both the
      CFM and the conventional EEG tracings. The patients with ICH showed depressed
      amplitudes, an increase in discontinuous activity, and a high incidence of
      seizure activity. The patients with HIE were characterized by depressed
      activities correlating with the severity of the pathology. Our results indicate
      that the CFM is a very helpful tool for neurophysiological surveillance in high
      risk neonates.

PMID- 11585330
TI  - Repeat endoscopic third ventriculostomy: is it worth trying?
AB  - OBJECT: The goal of this study was to evaluate the safety, efficacy, and
      indications for repeat endoscopic third ventriculostomies (ETV). METHODS AND
      RESULTS: We reviewed the records of 20 patients who had undergone repeat ETV from
      1987 to 1999. Their ages ranged from 8 months to 53 years (mean 17 years). The
      primary etiologies of hydrocephalus were: primary aqueductal stenosis (9 cases),
      tumor (5), Chiari malformation (2), prior infection (2), prior intraventricular
      hemorrhage (1), and blocked foramen of Monro (1 patient). The interval between
      the first and second ETVs ranged from 8 days to almost 6 years (mean 12.8
      months). The intraoperative findings at repeat surgery were: occlusion of the
      primary orifice by scar (10 cases), virginal floor of the third ventricle (5
      cases), pinhole ventriculostomy (3 cases), incompletely penetrated membrane (1
      case), and blood clot occluding the orifice (1 case). The follow-up period ranged
      from 3 to 47 months (median 20 months). Repeat ETV was successful in 13 patients
      (65%). These patients did not require further shunting or other procedures during
      follow-up. Seven patients (35%) required placement of a shunt after repeat ETV.
      Several complications were observed in 1 patient (5%), including seizures,
      elevated ICP, bilateral pulmonary edema, and cardiac arrhythmia. This patient
      ultimately recovered fully; the ETV was successful, and the patient did not
      require a shunt. CONCLUSIONS: Based on the experience of this group of patients,
      repeat ETV is as effective and as safe as a primary ETV procedure, and should be
      attempted in selected patients.

PMID- 11585331
TI  - Selective posterior rhizotomy in children with cerebral palsy: a 10-year
      experience.
AB  - We reviewed our 10-year experience of selective posterior rhizotomy (SPR), with
      an emphasis on surgical outcome concentrated on improvements in functional
      ability and adverse effects. We had performed SPR in 208 patients between 1990
      and 1999. All patients showed an overall improvement (over 95%) in spasticity,
      passive range of motion, and gait pattern. Preoperative ambulatory functional
      level and age were very important predictive factors for further improvements in
      postoperative functional ability. Compared with the younger children, the older
      ones lacked a full range of motion preoperatively, and they continued to lack a
      full range of motion postoperatively, despite the decrease in tone achieved by
      SPR. Most postoperative complications such as hypotonia, urinary retention,
      spinal deformities, and sensory changes were temporary and not functionally
      important. We conclude that SPR is an effective method of alleviating spasticity
      and provides lasting functional benefits at acceptable complication levels in
      spastic children with cerebral palsy.

PMID- 11585332
TI  - The use of chemotherapy to facilitate surgical resection in pleomorphic
      xanthoastrocytoma: experience in a single case.
AB  - The use of noncytotoxic chemotherapy as an adjuvant treatment to permit resection
      of a pleomorphic xanthoastrocytoma (PXA) is described. A 6-year-old girl with a
      large right occipito-temporo-parietal lesion presented with signs and symptoms of
      raised intracranial pressure. An initial attempt at resection was halted because
      of excessive blood loss, and tumour embolisation was not feasible as no suitable
      vascular pedicle was identified. Two cycles of vincristine and carboplatin were
      given, and these decreased the vascularity of the tumour allowing subsequent
      complete macroscopic resection 9 weeks later. The use of chemotherapy to decrease
      the vascularity of the tumour by way of its antiangiogenic effects is discussed.

PMID- 11585333
TI  - Hypothalamic tumour with haemorrhage.
AB  - Haemorrhage in low-grade glioma is rare. A 4-year-old boy presented with sudden
      loss of consciousness. CT scan of his head revealed anterior third ventricular
      tumour with bleeding, intraventricular haemorrhage and hydrocephalus. The boy
      expired within 26 h of the onset of his illness, and an autopsy revealed a
      haemorrhagic juvenile pilocytic astrocytoma arising from the lateral hypothalamus
      with intraventricular haemorrhage. Intracranial tumour as the cause of sudden
      death and tumour with bleeding are discussed.

PMID- 11585334
TI  - Primitive neuroectodermal tumor involving the frontal skull base in an infant.
AB  - We report here a case of a primitive neuroectodermal tumor involving the frontal
      skull base in a 5-month-old male infant. He presented with rapidly progressing
      exophthalmos on the left side. Preoperative magnetic resonance imaging revealed a
      well-demarcated, enhanced mass of 6 cm in diameter in the intradural extra-axial
      frontal region. The tumor was totally removed by surgery. Pathological findings
      were consistent with a primitive neuroectodermal tumor (PNET). Intradural extra
      axial PNET is very rare, and its prognosis is poor.

PMID- 11585335
TI  - Potent and selective inhibition of human cathepsin K leads to inhibition of bone
      resorption in vivo in a nonhuman primate.
AB  - Cathepsin K is a cysteine protease that plays an essential role in osteoclast
      mediated degradation of the organic matrix of bone. Knockout of the enzyme in
      mice, as well as lack of functional enzyme in the human condition
      pycnodysostosis, results in osteopetrosis. These results suggests that inhibition
      of the human enzyme may provide protection from bone loss in states of elevated
      bone turnover, such as postmenopausal osteoporosis. To test this theory, we have
      produced a small molecule inhibitor of human cathepsin K, SB-357114, that
      potently and selectively inhibits this enzyme (Ki = 0.16 nM). This compound
      potently inhibited cathepsin activity in situ, in human osteoclasts (inhibitor
      concentration [IC]50 = 70 nM) as well as bone resorption mediated by human
      osteoclasts in vitro (IC50 = 29 nM). Using SB-357114, we evaluated the effect of
      inhibition of cathepsin K on bone resorption in vivo using a nonhuman primate
      model of postmenopausal bone loss in which the active form of cathepsin K is
      identical to the human orthologue. A gonadotropin-releasing hormone agonist
      (GnRHa) was used to render cynomolgus monkeys estrogen deficient, which led to an
      increase in bone turnover. Treatment with SB-357114 (12 mg/kg subcutaneously)
      resulted in a significant reduction in serum markers of bone resorption relative
      to untreated controls. The effect was observed 1.5 h after the first dose and was
      maintained for 24 h. After 5 days of dosing, the reductions in N-terminal
      telopeptides (NTx) and C-terminal telopeptides (CTx) of type I collagen were 61%
      and 67%, respectively. A decrease in serum osteocalcin of 22% was also observed.
      These data show that inhibition of cathepsin K results in a significant reduction
      of bone resorption in vivo and provide further evidence that this may be a viable
      approach to the treatment of postmenopausal osteoporosis.

PMID- 11585336
TI  - Cathepsin K, osteoclastic resorption, and osteoporosis therapy.

PMID- 11585337
TI  - Angiomatosis of bone with localized mineralization defect.

PMID- 11585338
TI  - The loss of Smad3 results in a lower rate of bone formation and osteopenia
      through dysregulation of osteoblast differentiation and apoptosis.
AB  - Smad3 is a well-characterized intracellular effector of the transforming growth
      factor beta (TGF-beta) signaling pathway and was implicated recently in the
      potentiation of vitamin D receptor (VDR)-mediated signaling. Given that both TGF
      beta and vitamin D are important regulators of bone remodeling, it is expected
      that Smad3 plays an integral role in normal maintenance of bone. However, the
      exact mechanisms by which Smad3 functions in bone remodeling are unknown. Here,
      we show that mice with targeted deletion of Smad3 are osteopenic with less
      cortical and cancellous bone compared with wild-type littermates. Decreases in
      bone mineral density (BMD) in Smad3 null mice reflect the inability of
      osteoblasts to balance osteoclast activity, although osteoclast numbers are
      normal and vitamin D mediated serum calcium homeostasis is maintained. The
      osteopenia of Smad3 null mice is attributed to a decreased rate of bone formation
      associated with increased osteocyte number and apoptosis. These findings are
      supported by studies with isolated primary osteoblasts that show TGF-beta can no
      longer inhibit the differentiation of osteoblasts in the absence of Smad3; yet,
      TGF-beta-stimulated proliferation remains intact. Together these data support a
      model that a loss of Smad3 increases the osteocyte fate of the osteoblast and
      decreases the duration of osteoblast function by shortening lifespan, ultimately
      resulting in osteopenia.

PMID- 11585339
TI  - Bone morphogenetic protein regulation of forkhead/winged helix transcription
      factor Foxc2 (Mfh1) in a murine mesodermal cell line C1 and in skeletal precursor
      cells.
AB  - Mfh1/Foxc2 is a member of forkhead/winged helix transcription factor family in
      which its members serve as key regulators in embryogenesis and cell
      differentiation in various species. Mutant mice null for Mfh1 show defects in
      axial and cranial skeletogenesis, suggesting requirement of Mfh1 for skeletal
      tissue development. However, the roles of Mfh1 and its regulation during early
      skeletogenesis have not been understood fully yet. In this study, we investigated
      developmental regulation of Mfh1 expression during embryonic skeletogenesis in
      vivo and in vitro chondrogenic cell differentiation using a mesodermal progenitor
      like cell line C1. We first examined expression patterns of Mfh1 in relation to
      the cartilage phenotype-related molecules including bone morphogenetic proteins
      (BMPs) during mouse embryogenesis by in situ hybridization. In 10.5 days
      postcoitum (dpc) mouse limb, Mfh1 messenger RNA (mRNA) was expressed in the
      mesenchymal cells in the tissues that later give rise to skeleton. In 11.5 dpc
      embryos, Mfh1 transcripts were expressed in the cell condensation of skeletal
      blastemas. BMP2 transcripts were expressed in the cell condensation proximal to
      the Mfh1-expressing cells in the limbs and those of BMP-7 were expressed in the
      mesenchymal tissue surrounding the Mfh1-positive cell condensation. In 12.5 dpc
      and 13.5 dpc embryos, the expression of Mfh1 was localized to the perichondrium,
      which surrounds cells that express noggin and SOX9 mRNA. BMP-2 expression was
      overlapped with that of Mfh1 in the peripheral layer of 12.5 dpc and 13.5 dpc
      limb skeletal blastemas. Mfh1 expression persisted in the perichondrium of 15.5
      dpc embryos though its level was reduced. We then examined the expression of Mfh1
      in the mouse mesodermal cell line C1 that differentiates into chondrocytes in
      vitro. Mfh1 mRNA was expressed constitutively at low levels in C1 cells before
      the induction of its differentiation. On the differentiation of C1 cells into
      chondrocytes by the treatment with dexamethasone (Dex), Mfh1 expression was
      increased and peaked on day 4 of Dex treatment. Treatment with BMP-4/7 and BMP-7
      protein also enhanced Mfh1 expression in C1 cells. To further examine the
      causative relationship between BMP and Mfh1 in mesenchymal tissue, we performed a
      mouse limb bud organ culture to implant BMP proteins with carriers into the
      mesenchymal tissue of the limb bud. Implantation of BMP-7 protein in the limb bud
      of 11.5 dpc embryos induced Mfh1 expression, suggesting that BMP regulates Mfh1
      expression in limb mesenchyme. These results indicate that Mfh1 expression is
      associated with the early stage of chondrogenic differentiation both in vivo and
      in vitro and that BMPs regulate Mfh1 expression in skeletal precursor cells.

PMID- 11585340
TI  - Focal adhesion kinase activity is required for bone morphogenetic protein--Smad1
      signaling and osteoblastic differentiation in murine MC3T3-E1 cells.
AB  - Cell-matrix interactions via integrins are essential for osteoblastic
      differentiation. We have shown that signals activated by aggregation of
      alpha2beta1-integrin with type I collagen are involved in the differentiation of
      osteoblastic MC3T3-E1 cells. Focal adhesion kinase (FAK) is an immediate
      downstream signal of the beta1-integrin, and inactivation of FAK has been shown
      to disrupt osteoblastic differentiation. To elucidate roles of FAK in
      osteoblastic cells, we examined MC3T3-E1 cells stably expressing antisense FAK
      (asFAK) messenger RNA (mRNA). Alkaline phosphatase (ALP) activity, an
      osteoblastic marker, did not increase in asFAK cells with a long-term culture
      until 21 days or in response to bone morphogenetic protein 2 (BMP-2). Treatment
      with BMP-2 also failed to stimulate the expression of osteocalcin in asFAK cells.
      In control MC3T3-E1 cells, BMP-2 induced translocation of Smad1 into nuclei to
      stimulate transcriptional activity of the Smad6 promoter gene that contains a
      Smad1 response element. In contrast, BMP-2 failed to increase transcriptional
      activity of Smad6 promoter gene in asFAK cells, although it induced nuclear
      translocation of Smad1. These results indicate that FAK was involved in Smad1
      dependent transcriptional activity but not in nuclear translocation of Smad1 in
      osteoblastic cells. Hence, FAK activation by integrins might converge
      transcriptional activation by BMP of its target genes in osteoblastic cells.
      These observations suggest that FAK activity is essential for BMP-Smad signaling
      to stimulate osteoblastic differentiation.

PMID- 11585341
TI  - Acid attack and cathepsin K in bone resorption around total hip replacement
      prosthesis.
AB  - Normal bone remodeling and pathological bone destruction have been considered to
      be osteoclast-driven. Osteoclasts are able to attach to bare bone surface and
      produce an acidic subcellular space. This leads to acid dissolution of
      hydroxyapatite, allowing cathepsin K to degrade the organic type I collagen-rich
      osteoid matrix under the acidic condition prevailing in Howship lacunae. Using a
      sting pH electrode, the interface membrane around a loosened total hip
      replacement prosthesis was found to be acidic. Confocal laser scanning disclosed
      irregular demineralization of the bone surface in contact with the acidic
      interface. Cathepsin K, an acidic collagenolytic enzyme, was found in interface
      tissue macrophages/giant cells and pseudosynovial fluid. Tissue extracts
      contained high levels of cathepsin K messenger RNA (mRNA) and protein. These
      observations suggest the presence of an acid- and cathepsin K-driven pathological
      mechanism of bone resorption, mediated not by osteoclasts in subosteoclastic
      space, but rather by the uncontrolled activity of macrophages in extracellular
      space.

PMID- 11585343
TI  - Antisense oligodeoxynucleotide evidence that a unique osteoclastic protein
      tyrosine phosphatase is essential for osteoclastic resorption.
AB  - This study tested the hypothesis that a unique osteoclastic transmembrane protein
      tyrosine phosphatase (PTP-oc) is involved in osteoclastic resorption by
      determining whether suppression of PTP-oc expression with a specific
      phosphorothioated 20-mer PTP-oc antisense oligodeoxynucleotide (oligo) would
      inhibit basal, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-stimulated, and PTH
      stimulated osteoclastic resorption. Treatment of rabbit osteoclasts with 1 microM
      of the antisense oligo for up to 4 days showed a time-dependent reduction in PTP
      oc protein level, indicating that this PTP-oc antisense oligo was effective. To
      assess the effect of PTP-oc antisense oligo on osteoclastic resorption, rabbit
      osteoclasts were pretreated for 3 days with 1 microM of the antisense, a scramble
      oligo, or vehicle, respectively, followed by a 3-day treatment with vehicle, 10
      nM of 1,25(OH)2D3, or 10 nM of parathyroid hormone (PTH). 1,25(OH)2D3 and PTH
      each alone increased PTP-oc cellular level and stimulated resorptive activity of
      rabbit osteoclasts. The antisense oligo treatment, but not the scramble oligo,
      decreased the basal and the stimulated resorption activity and reduced the PTP-oc
      protein level. Treatment with the PTP-oc antisense oligo, but not the scramble
      oligo, also markedly increased the Y527 phosphorylation level of c-src in rabbit
      osteoclasts. In conclusion, these results provide the first antisense oligo
      evidence that PTP-oc plays an essential role in osteoclastic resorption.

PMID- 11585342
TI  - Transforming growth factor beta affects osteoclast differentiation via direct and
      indirect actions.
AB  - Transforming growth factor beta (TGF-beta) is abundant in bone and has complex
      effects on osteolysis, with both positive and negative effects on osteoclast
      differentiation, suggesting that it acts via more than one mechanism.
      Osteoclastogenesis is determined primarily by osteoblast (OB) expression of the
      tumor necrosis factor (TNF)-related molecule receptor activator of NF-kappaB
      ligand (RANKL) and its decoy receptor osteoprotegerin (OPG), which are increased
      and decreased, respectively, by osteolytic factors. A RANKL-independent
      osteoclastogenic mechanism mediated by TNF-alpha has also been shown. Therefore,
      we investigated TGF-beta effects on osteoclast formation in culture systems in
      which osteoclastogenic stimulus is dependent on OBs and culture systems where it
      was provided by exogenously added RANKL or TNF-alpha. Both OPG and TGF-beta
      inhibited osteoclast formation in hemopoietic cell/OB cocultures, but the
      kinetics of their action differed. TGF-beta also inhibited osteoclastogenesis in
      cocultures of cells derived from OPG null (opg-/-) mice. TGF-beta strongly
      decreased RANKL messenger RNA (mRNA) expression in cultured osteoblasts, and
      addition of exogenous RANKL to TGFbeta-inhibited cocultures of opg-/- cells
      partially restored osteoclastogenesis. Combined, these data indicate that the
      inhibitory actions of TGF-beta were mediated mainly by decreased OB production of
      RANKL. In contrast, in the absence of OBs, TGF-beta greatly increased osteoclast
      formation in recombinant RANKL- or TNF-alpha-stimulated cultures of hemopoietic
      cells or RAW 264.7 macrophage-like cells to levels several-fold greater than
      attainable by maximal stimulation by RANKL or TNF-alpha. These data suggest that
      TGF-beta may increase osteoclast formation via action on osteoclast precursors.
      Therefore, although RANKL (or TNF-alpha) is essential for osteoclast formation,
      factors such as TGF-beta may powerfully modify these osteoclastogenic stimuli.
      Such actions may be critical to the control of physiological and
      pathophysiological osteolysis.

PMID- 11585344
TI  - Osteoclast inhibitory peptide 2 inhibits osteoclast formation via its C-terminal
      fragment.
AB  - Osteoclast inhibitory peptide 2 (OIP-2) is a novel autocrine/paracrine factor
      produced by osteoclasts (OCLs) that inhibits bone resorption and OCL formation in
      vitro and in vivo. It is identical to the asparaginyl endopeptidase legumain.
      During maturation of OIP-2, a signal peptide and a 17-kDa C-terminal fragment
      (CTF) are cleaved to produce the mature enzyme. To determine if enzyme activity
      is required for inhibition of OCL formation or if only the CTF is responsible for
      these effects, we synthesized His-tagged complementary DNA (cDNA) constructs for
      the CTF of OIP-2, the proform of OIP-2, and the "mature enzyme" form of OIP-2.
      The proform or the CTF portion of OIP-2 inhibited OCL formation in a dose
      dependent manner in murine bone marrow cultures stimulated with 1,25
      dihydroxyvitamin D3 [1,25(OH)2D3]. The mature form of OIP-2, which was
      enzymatically active, did not inhibit OCL formation. In addition, OIP-2 inhibited
      OCL formation in cultures of highly purified human OCL precursor cells or
      RAW264.7 cells stimulated with 10 ng/ml of receptor activator of NF-kappaB (RANK)
      ligand. Binding studies with His-tagged OIP-2 showed expression of a putative OIP
      2 receptor on RAW264.7 cells treated with RANK ligand for 4 days and human marrow
      cultures treated with 1,25(OH)2D3 for 3 weeks. These data show that the CTF of
      OIP-2, rather than the mature enzyme, mediates the inhibitory effects of OIP-2
      through a putative receptor on OCL precursors.

PMID- 11585345
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on bone in two rat strains with
      different aryl hydrocarbon receptor structures.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs) are highly toxic environmental
      contaminants, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent
      dioxin. Here, we studied the effects of TCDD on bone. Two rat strains, Han/Wistar
      (H/W) and Long-Evans (L-E), were used because they exhibit a 1000-fold
      sensitivity difference in acute lethality of TCDD, which difference is related to
      the aryl hydrocarbon receptor (AHR). TCDD inhibited the tibial growth dose
      dependently, the effect being manifested at lower doses in the more sensitive L-E
      strain. In H/W rats the effect of TCDD was seen only at the high dose of 170
      microg/kg (p < 0.05), whereas in the sensitive L-E rats a significant reduction
      of bone growth was already seen at 1.7 microg/kg (p < 0.01). This reduction was
      caused by the smaller tibial size because the diaphyseal bone mineral density
      (BMD) did not change. The three-point bending breaking force of the tibia was
      significantly reduced in H/W rats at 170 microg/kg (p < 0.05), but tibial
      stiffness was lower already at the dose of 17 microg/kg (p < 0.05). In the
      sensitive L-E strain, both breaking force and stiffness were reduced at the dose
      of 17 microg/kg (p < 0.001). These results indicate that TCDD dose-dependently
      interferes with bone growth, modeling, and mechanical strength. The altered
      transactivation domain of AHR is associated with a lower sensitivity of bone to
      TCDD in H/W rats, suggesting that AHR plays a role in modulating the effects of
      dioxins on bone.

PMID- 11585346
TI  - Spectroscopic characterization of collagen cross-links in bone.
AB  - Collagen is the most abundant protein of the organic matrix in mineralizing
      tissues. One of its most critical properties is its cross-linking pattern. The
      intermolecular cross-linking provides the fibrillar matrices with mechanical
      properties such as tensile strength and viscoelasticity. In this study, Fourier
      transform infrared (FTIR) spectroscopy and FTIR imaging (FTIRI) analyses were
      performed in a series of biochemically characterized samples including purified
      collagen cross-linked peptides, demineralized bovine bone collagen from animals
      of different ages, collagen from vitamin B6-deficient chick homogenized bone and
      their age- and sex-matched controls, and histologically stained thin sections
      from normal human iliac crest biopsy specimens. One region of the FTIR spectrum
      of particular interest (the amide I spectral region) was resolved into its
      underlying components. Of these components, the relative percent area ratio of
      two subbands at approximately 1660 cm(-1) and approximately 1690 cm(-1) was
      related to collagen cross-links that are abundant in mineralized tissues (i.e.,
      pyridinoline [Pyr] and dehydrodihydroxylysinonorleucine [deH-DHLNL]). This study
      shows that it is feasible to monitor Pyr and DHLNL collagen cross-links spatial
      distribution in mineralized tissues. The spectroscopic parameter established in
      this study may be used in FTIRI analyses, thus enabling the calculation of
      relative Pyr/DHLNL amounts in thin (approximately 5 microm) calcified tissue
      sections with a spatial resolution of approximately 7 microm.

PMID- 11585347
TI  - Cooperative effects of exercise training and genistein administration on bone
      mass in ovariectomized mice.
AB  - We reported that genistein, a soybean isoflavone, prevents bone loss caused by
      estrogen deficiency, without undesirable effects on the uterus. In this study, we
      examined cooperative effects of genistein administration and running exercise on
      bone mass in ovariectomized (OVX) mice. Female mice aged 7 weeks were either sham
      operated or OVX and divided into six groups: (1) sham; (2) OVX; (3) OVX, treated
      with genistein at a submaximal dose (0.4 mg/day) subcutaneously (G); (4) OVX,
      exercised on a treadmill daily for 30 minutes/day at 12 m/minute on a 10 degree
      uphill slope (Ex); (5) OVX, given genistein and exercised (ExG); and (6) OVX,
      treated with 17beta-estradiol (0.03 microg/day) in the same manner as genistein
      (E2). Four weeks after intervention, bone mass was estimated by dual-energy X-ray
      absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). Bone
      mineral density (BMD) of the whole femur measured by DXA was higher in both the G
      and the Ex groups than in the OVX group. Furthermore, BMD in the ExG group was
      significantly higher than that in the groups receiving either intervention alone.
      Bone area in distal region of the femur was significantly higher in Ex and ExG
      groups as compared with those in the OVX and G groups. pQCT analysis showed that
      the cross-sectional areas (CSAs) and periosteum perimeter at midshaft of the
      femur did not differ in the sham and OVX groups but were significantly higher in
      Ex and ExG groups. Histomorphometric analysis showed that bone formation
      rate/bone surface (BFR/BS) was significantly higher in both Ex and ExG groups as
      compared with that in non-exercised groups. The bone volume (BV/TV) in the distal
      femoral cancellous bone was lower in the OVX than that in the sham group, and it
      was restored completely in the ExG group, as in the E2 group. Thickness of the
      trabecular bone (Tb.Th) was higher in Ex and ExG groups than that in the OVX and
      G groups. These results indicate that the combined intervention of moderate
      exercise and the submaximal dose of genistein administration show a cooperative
      effect in preventing bone loss in OVX mice.

PMID- 11585348
TI  - Accelerated up-regulation of L-Sox5, Sox6, and Sox9 by BMP-2 gene transfer during
      murine fracture healing.
AB  - Fracture repair is the best-characterized situation in which activation of
      chondrogenesis takes place in an adult organism. To better understand the
      mechanisms that regulate chondrogenic differentiation of mesenchymal progenitor
      cells during fracture repair, we have investigated the participation of
      transcription factors L-Sox5, Sox6, and Sox9 in this process. Marked up
      regulation of L-Sox5 and Sox9 messenger RNA (mRNA) and smaller changes in Sox6
      mRNA levels were observed in RNAse protection assays during early stages of
      callus formation, followed by up-regulation of type II collagen production.
      During cartilage expansion, the colocalization of L-Sox5, Sox6, and Sox9 by
      immunohistochemistry and type II collagen transcripts by in situ hybridization
      confirmed a close relationship of these transcription factors with the
      chondrocyte phenotype and cartilage production. On chondrocyte hypertrophy,
      production of L-Sox5, Sox9 and type II collagen were down-regulated markedly and
      that of type X collagen was up-regulated. Finally, using adenovirus mediated bone
      morphogenetic protein 2 (BMP-2) gene transfer into fracture site we showed
      accelerated up-regulation of the genes for all three Sox proteins and type II
      collagen in fractures treated with BMP-2 when compared with control fractures.
      These data suggest that L-Sox5, Sox6, and Sox9 are involved in the activation and
      maintenance of chondrogenesis during fracture healing and that enhancement of
      chondrogenesis by BMP-2 is mediated via an L-Sox5/Sox6/Sox9-dependent pathway.

PMID- 11585349
TI  - Effects of daily treatment with parathyroid hormone on bone microarchitecture and
      turnover in patients with osteoporosis: a paired biopsy study.
AB  - We examined paired iliac crest bone biopsy specimens from patients with
      osteoporosis before and after treatment with daily injections of 400 U of
      recombinant, human parathyroid hormone 1-34 [PTH(1-34)]. Two groups of patients
      were studied. The first group was comprised of 8 men with an average age 49
      years. They were treated with PTH for 18 months. The second group was comprised
      of 8 postmenopausal women with an average age 54 years. They were treated with
      PTH for 36 months. The women had been and were maintained on hormone replacement
      therapy for the duration of PTH treatment. Patients were supplemented to obtain
      an average daily intake of 1500 mg of elemental calcium and 100 IU of vitamin D.
      The biopsy specimens were subjected to routine histomorphometric analysis and
      microcomputed tomography (CT). Cancellous bone area was maintained in both
      groups. Cortical width was maintained in men and significantly increased in
      women. There was no increase in cortical porosity. There was a significant
      increase in the width of bone packets on the inner aspect of the cortex in both
      men and women. This was accompanied by a significant decrease in eroded perimeter
      on this surface in both groups. Micro-CT confirmed the foregoing changes and, in
      addition, revealed an increase in connectivity density, a three dimensional (3D)
      measure of trabecular connectivity in the majority of patients. These findings
      indicate that daily PTH treatment exerts anabolic action on cortical bone in
      patients with osteoporosis and also can improve cancellous bone
      microarchitecture. The results provide a structural basis for the recent
      demonstration that PTH treatment reduces the incidence of osteoporosis-related
      fractures.

PMID- 11585350
TI  - Bone brittleness varies with genetic background in A/J and C57BL/6J inbred mice.
AB  - The contribution of genetic and environmental factors to variations in bone
      quality are understood poorly. We tested whether bone brittleness varies with
      genetic background using the A/J and C57BL/6J inbred mouse strains. Whole bone
      four-point bending tests revealed a 70% decrease in postyield deflection of A/J
      femurs compared with C57BL/6J, indicating that A/J femurs failed in a
      significantly more brittle manner. Cyclic loading studies indicated that A/J
      femurs accumulated damage differently than C57BL/6J femurs, consistent with their
      increased brittleness. Differences in matrix composition also were observed
      between the two mouse strains. A/J femurs had a 4.5% increase in ash content and
      an 11.8% decrease in collagen content. Interestingly, a reciprocal relationship
      was observed between femoral geometry and material stiffness; this relationship
      may have contributed to the brittle phenotype of A/J femurs. A/J femurs are more
      slender than those of C57BL/6J femurs; however, their 47% smaller moment of
      inertia appeared to be compensated by an increased tissue stiffness at the
      expense of altered tissue damageability. Importantly, these differences in whole
      bone mechanical properties between A/J and C57BL/6J femurs could not have been
      predicted from bone mass or density measures alone. The results indicated that
      bone brittleness is a genetically influenced trait and that it is associated with
      genetically determined differences in whole bone architecture, bone matrix
      composition, and mechanisms of cyclical damage accumulation.

PMID- 11585351
TI  - Prevalence and causes of low bone density and fractures in kidney transplant
      patients.
AB  - Osteoporosis is known to occur in patients with kidney transplants, but limited
      information is available about the prevalence and causes of this complication. We
      asked all 330 patients with kidney transplants in our unit to participate in this
      study of whom 165 (50%) agreed to do so. The characteristics of the participating
      patients were similar to the remaining 165 nonparticipants. Seventy of 165 (42%)
      of the participants were women of whom 40 were postmenopausal in contrast to the
      men of whom only one was hypogonadal. Bone mineral density (BMD) was
      significantly reduced at the radius (Z score, -1.5) and femoral neck (Z score, 
      0.7), but the lumbar spine was normal. BMD was lower in women than men at all
      skeletal sites. Osteoporosis was found in 10-44% and osteopenia was found in 35
      50% of women depending on the site. BMD was related inversely to time since
      transplantation and cumulative prednisolone dose. Twenty-seven of the 165 (16%)
      patients had either vertebral deformities or a history of a low trauma fracture
      after transplantation. This fracture group consisted of 10/27 (37%) men and 17/27
      (63%) women, of whom 14 were postmenopausal. Fracture patients tended to be older
      and have a longer duration of renal failure, dialysis, transplantation, greater
      cumulative steroid dose, and higher bone resorption markers than the nonfracture
      group. No differences were found for cumulative doses of cyclosporin or
      tacrolimus. Logistic regression showed that only duration of dialysis and time
      since transplantation significantly increased fracture risk, with odds ratio (OR)
      for each year of dialysis or transplantation being 1.21 (CI, 1.00-1.48) and 1.14
      (CI, 1.05-1.23), respectively. These data show that low bone density and
      fractures are common in patients with kidney transplant and are determined by
      both pre- and posttransplant variables. Fracture risk was greatest in women,
      particularly if they were postmenopausal and we recommend that this subgroup is
      targeted for assessment and treatment.

PMID- 11585352
TI  - Ibandronate: a comparison of oral daily dosing versus intermittent dosing in
      postmenopausal osteoporosis.
AB  - The objective of this study was to compare efficacy and safety of continuous
      versus intermittent oral dosing of ibandronate. Two hundred forty women aged 55
      75 years with postmenopausal osteoporosis were randomized to active treatment or
      placebo. Similar total doses of ibandronate were provided by treatment regimens
      with either continuous 2.5 mg of ibandronate daily (n = 81) or intermittent 20 mg
      of ibandronate every other day for the first 24 days, followed by 9 weeks without
      active drug (n = 78). The placebo group (total, n = 81) was crossed over after 12
      months to receive either continuous (n = 37) or intermittent ibandronate (n =
      35). By 24 months, bone mineral density (BMD) had increased significantly
      relative to baseline in both active treatment groups. The continuous and
      intermittent groups showed statistically equivalent increases in lumbar spine BMD
      of +5.64% (+/-0.53) and +5.54% (+/-0.53) and in total hip of +3.35% (+/-0.40) and
      +3.41% (+/-0.40), respectively (per protocol population). Biochemical markers of
      bone turnover decreased significantly in both treatment groups. The level of
      marker suppression was similar, although the intermittent group displayed, as
      expected, more fluctuation over the treatment period. The frequency of adverse
      events was similar in the treatment groups. In conclusion, the intermittent and
      continuous regimens showed equivalent changes in BMD and bone turnover. These
      results confirm previous preclinical findings indicating that the efficacy of
      ibandronate depends on the total oral dose given rather than on the dosing
      schedule. This supports development of new flexible dosing regimens targeted to
      minimize the frequency of dosing, which are expected to improve convenience and
      lead to enhanced long-term patient compliance.

PMID- 11585353
TI  - Glucocorticoid excess during adolescence leads to a major persistent deficit in
      bone mass and an increase in central body fat.
AB  - Endogenous Cushing's syndrome (CS) in children causes growth retardation,
      decreased bone mass, and increased total body fat. No prospective controlled
      studies have been performed in children to determine the long-term sequelae of CS
      on peak bone mass and body composition. A 15-year-old girl with Cushing disease
      (CD), and her healthy identical co-twin, were followed for 6 years after the CD
      was cured. At the 6-year follow-up both twins had areal bone mineral density
      (BMD) and body composition determined by dual-energy X-ray absorptiometry (DXA)
      and three-dimensional quantitative computed tomography (3DQCT). Z scores for
      height, weight, and body mass index (BMI) were -2.3, -0.8 and 0.2, and 1.2, 0.2,
      and -0.6, in the twin with CD and her co-twin, respectively. In the twin with CD,
      areal BMD and bone mineral apparent density (BMAD) at different sites varied from
      0.7 to 3 SD below her co-twin. Volumetric lumbar spine bone density Z score was 
      0.75 and 1.0, and total body, abdominal visceral, and subcutaneous fat (%) was
      42, 10, and 41 versus 26, 4, and 17 in the twin with CD and her co-twin,
      respectively. The relationship between total body fat and L2-L4 BMAD was inverse
      in the twin with CD (p < 0.05), which by contrast in her co-twin was opposite and
      direct (p < 0.001). In the twin with CD, despite cure, there was a persistent
      deficit in bone mass and increase in total and visceral body fat. These
      observations suggest that hypercortisolism (exogenous or endogenous) during
      adolescence may have persistent adverse effects on bone and fat mass.

PMID- 11585354
TI  - Quantitative ultrasound and trabecular architecture in the human calcaneus.
AB  - Relationships between quantitative ultrasound (QUS), density (bone volume density
      [BV/TV]), and trabecular architecture were investigated in 69 calcaneal
      cancellous bone cubes. Ultrasound signal velocity, phase velocity, attenuation,
      and broadband ultrasonic attenuation (BUA) measurements were made along the
      mediolateral axis. Density and architectural parameters were measured using
      microcomputed tomography (microCT). Density yielded the best correlations with
      QUS (r2 = 73-77%). Of the individual architectural parameters, correlations with
      QUS were highest for the Structure Model Index (SMI), a parameter quantifying the
      relative proportion of rods and plates (r2 = 57-63%). After adjustment for
      density, significant associations with QUS remained for SMI, trabecular spacing
      (Tb.Sp), and trabecular number (Tb.N), although the variance in QUS attributable
      uniquely to individual architectural parameters was at best 4%. In multivariate
      regression models, combinations of density and architectural parameters explained
      76-82% of the variance in QUS, representing an r2 increase of, at most, 8%
      compared with using density alone. However, multivariate models using
      combinations of architectural parameters alone (i.e., density excluded) also had
      a good predictive ability for QUS (r2 = 73-81%). Thus, although these data show
      modest but significant density-independent relationships between QUS and
      trabecular architecture in the human calcaneus for the first time, the causal
      relationships behind the variation in acoustic properties remain obscure. Given
      the relative weakness and complexity of the emerging associations between QUS and
      architecture, it is prudent to regard QUS measurements in calcaneal bone
      primarily as an indicator of bone density.

PMID- 11585355
TI  - Bone mineral density and fracture among prevalent kidney stone cases in the Third
      National Health and Nutrition Examination Survey.
AB  - Concern that people who form kidney stones may have reduced bone mineral density
      (BMD) and increased fracture risk has motivated clinical and population-based
      studies, but findings are inconsistent. In this cross-sectional study, we use the
      Third National Health and Nutrition Examination Survey (NHANES III) to determine
      whether a history of kidney stones (n = 793) is associated with lower femoral
      neck BMD and whether the association is similar for men and women. We further ask
      whether dietary calcium modifies the association between kidney stone history and
      BMD and whether there is an association between kidney stone history and
      prevalent spine or wrist fracture. We find that men with kidney stone history
      have lower femoral neck BMD than men without kidney stone history after adjusting
      for age, body mass index (BMI), race/ethnicity, and other potential confounders.
      The effect of kidney stone history on BMD is weaker for women. Men with kidney
      stone history also are more likely to report prevalent wrist and spine fractures.
      Dietary calcium, represented by usual milk consumption, is associated positively
      with BMD for both men and women and modifies the effect of kidney stone history
      on BMD for men. For men who form kidney stones, milk consumption is associated
      more strongly with femoral neck BMD than for men without such a history. The
      effect modification is such that the difference in BMD between men with and
      without kidney stone history is observed only at lower levels of milk
      consumption.

PMID- 11585356
TI  - Vitamin A antagonizes calcium response to vitamin D in man.
AB  - For unknown reasons, the highest incidence of osteoporosis is found in northern
      Europe. In these populations, the sunlight exposure is limited and the vitamin A
      intake is high. The interaction between vitamin A and D has been the subject of
      several in vitro and animal studies. We have studied the acute effects of vitamin
      A and D on calcium homeostasis in 9 healthy human subjects. We compared the
      effect of (i) 15 mg of retinyl palmitate, (ii) 2 microg of 1,25-dihydroxyvitamin
      D3 [1,25(OH)2D3], (iii) 15 mg of retinyl palmitate plus 2 microg of 1,25(OH)2D3,
      and (iv) placebo in a double-blind crossover study. The subjects took vitamin
      preparations at 10:00 p.m. and the following day blood samples were collected
      five times from 8:00 a.m. to 4:00 p.m. Serum levels of 1,25(OH)2D3 and retinyl
      esters increased (1.7-fold and 8.3-fold, respectively; p < 0.01). As expected,
      serum calcium (S-calcium) increased (2.3%; p < 0.01) and S-parathyroid hormone
      (PTH) decreased (-32%; p < 0.05) after 1,25(OH)2D3 intake. In contrast, retinyl
      palmitate intake resulted in a significant decrease in S-calcium when taken alone
      (-1.0%; p < 0.05) and diminished the calcium response to 1,25(OH)2D3 after the
      combined intake (1.4%; p < 0.01). S-PTH was unaffected by retinyl palmitate. No
      significant changes in serum levels of the degradation product of C-telopeptide
      of type I collagen (CrossLaps), or U-calcium/creatinine levels were found. In
      conclusion, an intake of vitamin A corresponding to about one serving of liver
      antagonizes the rapid intestinal calcium response to physiological levels of
      vitamin D in man.

PMID- 11585357
TI  - Regional and hormone-dependent effects of apolipoprotein E genotype on changes in
      bone mineral in perimenopausal women.
AB  - We studied 479 perimenopausal Danish women aged 45-58 years to examine
      differences between APOE genotypes with respect to (1) baseline total body bone
      mineral density (BMD) and densities measured in five different regions
      (ultradistal forearm, proximal forearm, lumbar spine, femoral neck, and total hip
      region); (2) serum levels of alkaline phosphatase, bone isoenzyme alkaline
      phosphatase, osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D, and
      urine hydroxyproline/creatinine excretion ratio; and (3) changes in bone mineral
      during 5 years of follow-up. Baseline BMDs were identical, whereas serum levels
      of alkaline phosphatase and its bone isoenzyme were higher in women with APOE 2-2
      and APOE 2-3 than in women with APOE 3-3 and APOE 3-4 and lower in women with
      APOE 4-4. Among women not receiving hormonal-replacement therapy (HRT; n = 262),
      those with APOE 2-2 and APOE 2-3 had 30-40% lower rates of femoral neck and total
      hip bone mineral loss than women with APOE 3-3 and APOE 3-4, whereas the rates of
      mineral loss in other skeletal regions did not differ between these APOE
      genotypes. Women with APOE 4-4 appeared to have lower rates of bone mineral loss
      in all regions. Women treated with hormones throughout the follow-up period (n =
      113) gained bone mineral, and women with APOE 3-4 and APOE 4-4 gained relatively
      more mineral than other women. A comparison of untreated and treated women with
      APOE 2-3, APOE 3-3, and APOE 3-4 suggests a possible modification of the effect
      of APOE genotype by HRT. In conclusion, the common APOE polymorphism has a
      complex effect on bone metabolism in perimenopausal Danish women including
      possible modification by hormone use: (1) among women not receiving HRT, those
      with APOE*2 have lower bone mineral losses in the femoral neck and hip region
      than other women, and (2) among women receiving HRT, those with APOE*4 gain more
      bone mineral than other women.

PMID- 11585358
TI  - Acidic fibroblast growth factor signaling inhibits peroxynitrite-induced death of
      osteoblasts and osteoblast precursors.
AB  - After trauma injury to the musculoskeletal system, conditions such as ischemia
      and inflammation involve excess production of superoxide (O2*), nitric oxide
      (*NO), and their reaction product, peroxynitrite (ONOO-). Exposure of murine
      osteoblasts and rat-derived primary osteoblast precursors to ONOO- resulted in a
      dose- and time-dependent delayed cell death that was more characteristic of
      apoptosis than necrosis. Exposure of both cell populations to ONOO- immediately
      enhanced phosphorylation and nitration of tyrosine residues within several
      polypeptides. Treatment of osteoblasts and osteoblast precursors with exogenous
      acidic fibroblast growth factor (FGF-1) enhanced cellular growth, increased
      endogenous levels of tyrosine phosphorylation, and significantly induced
      expression of both osteopontin and osteocalcin messenger RNA (mRNA) as well as
      osteopontin protein. Pretreatment of both cell populations with exogenous FGF-1
      prevented ONOO(-)-mediated death. Cell signaling induced by FGF-1 pretreatment
      had no major effect of total levels of tyrosine nitration after ONOO- treatment.
      Collectively, these in vitro efforts show that FGF-1 signaling renders
      osteoblasts and osteoblast precursors resistant to the cytotoxic effects of ONOO
      . Consequently, results presented here predict the therapeutic use of this growth
      factor for promoting the progression of bone repair mechanisms after fracture
      trauma.

PMID- 11585359
TI  - Hypoparathyroidism associated with aneurysm of the left subclavian artery
      (Kommerell's diverticulum) in an adult patient with a chromosome 22q11.2
      deletion.
AB  - Hypoparathyroidism may either be acquired or of congenital origin. From the
      latter group, which represents a minority of cases, agenesis or hypoplasia of the
      parathyroid glands resulting in symptomatic hypocalcemia in the newborn or infant
      frequently is caused by a microdeletion of chromosome 22q11.2. We describe a man
      in whom hypoparathyroidism was first diagnosed at the age of 59 years. The
      endocrine disorder was found to be associated with this chromosome imbalance and
      also with an aneurysm of the left subclavian artery (Kommerell's diverticulum)
      compressing the esophagus and trachea. Given the potential implication for
      genetic counseling, a 22q11.2 deletion should be considered in the differential
      diagnosis of adult patients with hypoparathyroidism of unknown origin and should
      be searched for by appropriate molecular cytogenetic technique.

PMID- 11585360
TI  - What is said to be "statistically significant" should be demonstrably so.

PMID- 11585361
TI  - Methoxyamine potentiates DNA single strand breaks and double strand breaks
      induced by temozolomide in colon cancer cells.
AB  - We have previously shown that human cancer cells deficient in DNA mismatch repair
      (MMR) are resistant to the chemotherapeutic methylating agent temozolomide (TMZ)
      and can be sensitized by the base excision repair (BER) blocking agent
      methoxyamine (MX) [21]. To further characterize BER-mediated repair responses to
      methylating agent-induced DNA damage, we have now evaluated the effect of MX on
      TMZ-induced DNA single strand breaks (SSB) by alkaline elution and DNA double
      strand breaks (DSB) by pulsed field gel electrophoresis in SW480 (O6-alkylguanine
      DNA-alkyltransferase [AGT]+, MMR wild type) and HCT116 (AGT+, MMR deficient)
      colon cancer cells. SSB were evident in both cell lines after a 2-h exposure to
      equitoxic doses of temozolomide. MX significantly increased the number of TMZ
      induced DNA-SSB in both cell lines. In contrast to SSB, TMZ-induced DNA-DSB were
      dependent on MMR status and were time-dependent. Levels of 50 kb double stranded
      DNA fragments in MMR proficient cells were increased after TMZ alone or in
      combination with O6-benzylguanine or MX, whereas, in MMR deficient HCT116 cells,
      only TMZ plus MX produced significant levels of DNA-DSB. Levels of AP
      endonuclease, XRCC1 and polymerase beta were present in both cell lines and were
      not significantly altered after MX and TMZ. However, cleavage of a 30-mer double
      strand substrate by SW480 and HCT116 crude cell extracts was inhibited by MX plus
      TMZ. Thus, MX potentiation of TMZ cytotoxicity may be explained by the
      persistence of apurinic/apyrimidinic (AP) sites not further processed due to the
      presence of MX. Furthermore, in MMR-deficient, TMZ-resistant HCT116 colon cancer
      cells, MX potentiates TMZ cytotoxicity through formation of large DS-DNA
      fragmentation and subsequent apoptotic signalling.

PMID- 11585362
TI  - The major human abasic endonuclease: formation, consequences and repair of abasic
      lesions in DNA.
AB  - DNA continuously suffers the loss of its constituent bases, and thereby, a loss
      of potentially vital genetic information. Sites of missing bases--termed abasic
      or apurinic/apyrimidinic (AP) sites--form spontaneously, through damage-induced
      hydrolytic base release, or by enzyme-catalyzed removal of modified or mismatched
      bases during base excision repair (BER). In this review, we discuss the
      structural and biological consequences of abasic lesions in DNA, as well as the
      multiple repair pathways for such damage, while emphasizing the mechanistic
      operation of the multi-functional human abasic endonuclease APE1 (or REF-1) and
      its potential relationship to disease.

PMID- 11585363
TI  - Disparate effects of similar phenolic phytochemicals as inhibitors of oxidative
      damage to cellular DNA.
AB  - Phenolic phytochemicals are natural plant substances whose cellular effects have
      not been completely determined. Nordihydroguaiaretic acid (NDGA) and curcumin are
      two phenolic phytochemicals with similar molecular structures, suggesting that
      they possess comparable chemical properties particularly in terms of antioxidant
      activity. To examine this possibility in a cellular system, this study evaluated
      the capacities of NDGA and curcumin to function as antioxidants in inhibiting
      oxidative damage to DNA. Jurkat T-lymphocytes were pre-incubated for 30 min with
      0-25 microM of either NDGA or curcumin to allow for uptake. The phenolic
      phytochemical-treated cells were then oxidatively challenged with 25 microM
      hydrogen peroxide (H2O2). Afterwards, cells were subjected to alkaline micro-gel
      electrophoresis (i.e. comet assay) to assess the extent of single-strand breaks
      in DNA. In a concentration-dependent manner, NDGA inhibited H2O2-induced DNA
      damage, whereas curcumin did not. In fact, incubating Jurkat T-lymphocytes with
      curcumin alone actually induced DNA damage. This effect of curcumin on DNA did
      not appear to reflect the DNA fragmentation associated with apoptosis because
      there was no proteolytic cleavage of poly-(ADP-ribose)-polymerase, which is
      considered an early marker of apoptosis. Curcumin-induced damage to DNA was
      prevented by pre-treatment of the cells with the lipophilic antioxidant, alpha
      tocopherol, suggesting that curcumin damaged DNA through oxygen radicals.
      Therefore, it is concluded that NDGA has antioxidant activity but curcumin has
      prooxidant activity in cultured cells based on their opposite effects on DNA.

PMID- 11585364
TI  - The SOS-dependent upregulation of uvrD is not required for efficient nucleotide
      excision repair of ultraviolet light induced DNA photoproducts in Escherichia
      coli.
AB  - We have shown previously that induction of the SOS response is required for
      efficient nucleotide excision repair (NER) of the major ultraviolet light (UV)
      induced DNA lesion, the cyclobutane pyrimidine dimer (CPD), but not for repair of
      6-4 photoproducts (6-4PP) or for transcription-coupled repair of CPDs [1]. We
      have proposed that the upregulation of cellular NER capacity occurs in the early
      stages of the SOS response and enhances the rate of repair of the abundant yet
      poorly recognized genomic CPDs. The expression of three NER genes, uvrA, uvrB,
      and uvrD, is upregulated as part of the SOS response. UvrD differs from the
      others in that it is not involved in lesion recognition but rather in promoting
      the post-incision steps of NER, including turnover of the UvrBC incision complex.
      Since uvrC is not induced during the SOS response, its turnover would seem to be
      of great importance in promoting efficient NER. Here we show that the
      constitutive level of UvrD is adequate for carrying out efficient NER of both
      CPDs and 6-4PPs. Thus, the upregulation of uvrA and uvrB genes during the SOS
      response is sufficient for inducible NER of CPDs. We also show that cells with a
      limited NER capacity, in this case due to deletion of the uvrD gene, repair 6
      4PPs but cannot perform transcription-coupled repair of CPDs, indicating that the
      6-4PP is a better substrate for NER than is a CPD targeted for transcription
      coupled repair.

PMID- 11585365
TI  - Characterization of functional interactions among the Escherichia coli mismatch
      repair proteins using a bacterial two-hybrid assay.
AB  - Vsr mediates very short patch repair in Escherichia coli, correcting T/G
      mismatches caused by deamination of 5-methylcytosine to thymine. MutS and MutL,
      part of the post-replication mismatch repair system, stimulate VSP repair. In
      this study, we use a bacterial two-hybrid assay to show that MutL interacts with
      Vsr. We also show that interaction between Vsr and MutL inhibits the ability of
      MutL to dimerize, to interact with MutS and MutH and to mediate a previously
      unknown interaction between MutS and MutH. This inhibition may explain why high
      levels of Vsr are mutagenic in vivo. In addition, we show that the Mut fusion
      proteins are repair proficient in the bacterial two-hybrid assay, making it
      possible to study their interactions in various genetic backgrounds, or in the
      presence of DNA damaging agents.

PMID- 11585366
TI  - Effects of low iron conditions on the repair of DNA lesions induced by Cumene
      hydroperoxide in Escherichia coli cells.
AB  - In the present study, we evaluated the sensitivity of different Escherichia coli
      strains to Cumene hydroperoxide (CHP) treatment under distinct conditions of Fe2+
      availability. Our results showed that the pretreatment with an iron chelator
      (dipyridyl) protects all the tested strains against CHP toxic effects, but it was
      not sufficient to abolish the CHP induced mutagenesis. On the other hand,
      simultaneous pretreatment with both dipyridyl and neocuproine (copper chelator)
      leads to a complete protection against CHP mutagenic effects. Our data suggest
      the participation of copper ion in the CHP mutagenesis induced in E. coli.

PMID- 11585367
TI  - Increased DNA double strand breakage is responsible for sensitivity of the pso3-1
      mutant of Saccharomyces cerevisiae to hydrogen peroxide.
AB  - Escherichia coli endonuclease III (endo III) is the key repair enzyme essential
      for removal of oxidized pyrimidines and abasic sites. Although two homologues of
      endo III, Ntgl and Ntg2, were found in Saccharomyces cerevisiae, they do not
      significantly contribute to repair of oxidative DNA damage in vivo. This suggests
      that an additional activity(ies) or a regulatory pathway(s) involved in cellular
      response to oxidative DNA damage may exist in yeast. The pso3-1 mutant of S.
      cerevisiae was previously shown to be specifically sensitive to toxic effects of
      hydrogen peroxide (H2O2) and paraquat. Here, we show that increased DNA double
      strand breakage is very likely the basis of sensitivity of the pso3-1 mutant
      cells to H2O2. Our results, thus, indicate an involvement of the Pso3 protein in
      protection of yeast cells from oxidative stress presumably through its ability to
      prevent DNA double strand breakage. Furthermore, complementation of the repair
      defects of the pso3-1 mutant cells by E. coli endo III has been examined. It has
      been found that expression of the nth gene in the pso3-1 mutant cells recovers
      survival, decreases mutability and protects yeast genomic DNA from breakage
      following H2O2 treatment. This might suggest some degree of functional similarity
      between Pso3 and Nth.

PMID- 11585368
TI  - Autoantibodies to IA-2 and GAD65 in patients with type 2 diabetes mellitus of
      varied duration: prevalence and correlation with clinical features.
AB  - OBJECTIVE: To determine the prevalence of autoantibodies to IA-2 (IA-2Ab) and
      glutamic acid decarboxylase (GADAb) in type 2 diabetes, their relationship to
      disease duration, and their importance in management decisions. METHODS: We
      undertook a study of 101 patients with type 2 diabetes (defined as nonketotic
      hyperglycemia at diagnosis) of varied duration (median, 4 years). Results were
      compared with those from 36 patients with type 1 diabetes also of varied duration
      (median, 2 years). IA-2Ab and GADAb were measured by radioligand-binding assays
      with use of in vitro-synthesized, 35S-labeled antigens. RESULTS: Of the 101
      patients with type 2 diabetes, 20 (20%) were positive for GADAb; only 4 of these
      20 were positive for IA-2Ab. In comparison, 75% of patients with type 1 diabetes
      were positive for GADAb, IA-2Ab, or both (P<0.0001). The coincidence of IA-2Ab
      positivity in GADAb-positive patients with type 2 diabetes was significantly
      lower than in patients with type 1 diabetes (20% versus 73%, respectively; P =
      0.002). All four IA-2Ab- and GADAb-positive patients with type 2 diabetes
      required insulin and were younger than those positive for GADAb alone (P =
      0.018). GADAb positivity in patients with type 2 diabetes was highly associated
      with insulin requirement (P = 0.004), with an odds ratio of 5.8 in predicting
      insulin dependence. Among patients with type 2 diabetes receiving insulin
      therapy, disease duration was significantly shorter (P = 0.025) and body mass
      index was significantly lower (P<0.001) in GADAb-positive versus GADAb-negative
      patients. In contrast to type 1 diabetes, in which GADAb values were negatively
      correlated with disease duration (r = -0.34; P = 0.044), no significant
      correlation with disease duration was observed in type 2 diabetes (r = -0.166; P
      = 0.48). CONCLUSION: Irrespective of duration of disease, measurement of IA-2Ab
      and GADAb can help to identify those patients with type 2 diabetes most likely to
      require insulin therapy.

PMID- 11585369
TI  - Bone mineral density at time of clinical diagnosis of adult-onset type 1 diabetes
      mellitus.
AB  - OBJECTIVE: To study bone mineral density (BMD) and bone remodeling factors at the
      time of diagnosis of adult-onset type 1 diabetes mellitus (DM). METHODS: In 22
      men and 10 women, who ranged in age from 20 to 39 years, a study was undertaken
      promptly after diagnosis of type 1 DM (on the basis of criteria established by
      the World Health Organization). Before any treatment, the clinical history,
      glycemia, ketonuria, basal and glucagon-stimulated C-peptide levels, islet cell
      antibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), and bone
      remodeling variables were recorded for all the study subjects. Dual-energy x-ray
      absorptiometry (Hologic QDR1000) was performed to measure BMD in the lumbar spine
      (LS), femoral neck (FN), and Ward's triangle. RESULTS: Of the 32 patients, 24
      (75%) showed positive levels of ICA or GADA (or both), whereas 8 (25%) tested
      negative. The BMD values-Z-scores (standard deviation [SD] adjusted for age and
      sex)-were lower among the patients with DM than in a matched healthy population
      in both the LS (-0.61 +/- 1.23 SD; P = 0.008) and the FN (-0.38 +/- 1.00 SD; P =
      0.003). Twelve patients had a T-score between -2.5 SD and -1 SD in the LS, and 14
      had the same scores in the FN and were classified as having osteopenia. A
      correlation was found between BMD values and C-peptide levels in the LS (r =
      0.231; P = 0.02) and the FN (r = 0.27; P = 0.01). The BMD values did not
      correlate with bone remodeling markers, hemoglobin A1c, or immunologic variables.
      CONCLUSION: We found reduced bone mass in patients with type 1 DM at the time of
      the clinical diagnosis. A high percentage of patients with DM have osteopenia,
      which may not, therefore, be a late complication of type 1 DM. These findings
      need to be confirmed in larger studies.

PMID- 11585370
TI  - Thyroid nodules with microfollicular findings reported on fine-needle aspiration:
      invariably surgical treatment?
AB  - OBJECTIVE: To assess whether fine-needle aspiration (FNA) can be a diagnostic
      procedure for identification of malignant thyroid nodules when the smear reveals
      the cytologic (microfollicular) finding of "follicular neoplasm" (FN). METHODS:
      We reviewed a group of 79 patients with FN who underwent surgical treatment and
      evaluated the possible significance of the cytologic features of anisokaryosis,
      amount of colloid, and nuclear overlapping (NO). We excluded from the study those
      patients with FN who had other highly suspicious cytologic features, such as
      sporadic grooves and sporadic pseudonucleoli. RESULTS: In our series of 79
      patients with FN at FNA, we found anisokaryosis in 49.4%, scant or no colloid in
      31.6%, and NO in 5.1%. Thyroid cancer (TC)--follicular cancer or follicular
      variant of papillary cancer--was found in six patients (7.6%): four patients
      (10.2%) with anisokaryosis and two patients (5.0%) without anisokaryosis (P<0.5;
      chi2 test). All the patients with malignant lesions had scant or no colloid in
      the smears, and four of them were those with NO. Therefore, TC was found in 24.0%
      of nodules with scant or no colloid versus 0.0% of nodules with abundant colloid
      (P<0.001; chi2 test), and TC was found in 100% of nodules with NO versus 2.6% of
      nodules without NO (P<0.001; chi2 test). CONCLUSION: Because of the high
      prevalence of thyroid nodules and the frequency of FN at FNA, the number of
      unnecessary interventions may be very high. FNA cannot be diagnostic in FN
      because invasion of the tumor capsule and blood vessels can be evidenced only at
      histologic examination. Although it is common opinion that microfollicular
      nodules should be surgically treated, simple cytologic features can help select
      patients at low risk who can be monitored and reassessed clinically and by FNA.
      Patients with high-risk cytologic features such as NO should be advised that a
      total thyroidectomy may be necessary.

PMID- 11585371
TI  - Microvascular abnormalities in the bulbar conjunctiva of patients with type 2
      diabetes mellitus.
AB  - OBJECTIVE: To study and quantify microvascular abnormalities objectively in vivo
      in patients with type 2 diabetes mellitus (T2DM). METHODS: The conjunctival
      microcirculation in 14 patients with T2DM and in age-matched healthy control
      subjects without diabetes was videotaped and objectively studied by using
      computer-assisted intravital microscopy (CAIM), a novel and quantitative real
      time technology. RESULTS: Patients with T2DM (N = 14) had significantly (P<0.01)
      wider conjunctival vessel diameters (71.9 +/- 5.2 mm) than did healthy
      nondiabetic control subjects (54.0 +/- 4.4 mm). In the study patients,
      microvascular distribution was significantly (P<0.01) abnormal (36.7 +/- 18.2
      versus 45.3 +/- 9.6 cm per unit area, patients versus control subjects), and
      vessel distribution was uneven on the surface of the bulbar conjunctiva. The
      arteriole:venule (A:V) ratio in patients with T2DM was extremely variable and
      differed significantly (P<0.01) from that in the nondiabetic control subjects
      (A:V approximately 1:2). In addition, a unique sinusoidal (hypertensive) vascular
      pattern frequently existed in some of the large veins of all study patients with
      T2DM but in none of the nondiabetic control subjects. CONCLUSION: We identified
      the presence of microvascular changes (abnormalities) in the conjunctival
      microcirculation of patients with T2DM. Although all these abnormalities did not
      appear in the same patient at the same time, the sum total of their presence in
      each patient correlated significantly with disease severity, as noted in the
      medical records. The severity of microvascular abnormalities, however, did not
      correlate with the duration of the disease since diagnosis. CAIM may be a useful
      objective and quantitative technique for assessing microangiopathy in patients
      with T2DM. The easy noninvasive accessibility of the conjunctival vessels and the
      ability to identify and locate the same vessels repeatedly for longitudinal
      evaluations further emphasize the usefulness of this real-time technology.

PMID- 11585372
TI  - Beneficial effects of continuous subcutaneous insulin infusion in older patients
      with long-standing type 1 diabetes.
AB  - OBJECTIVE: To assess the effect of continuous subcutaneous insulin infusion
      (CSII) on glycemic control, hypoglycemia, and daily insulin requirements in five
      older patients with long-standing type 1 diabetes previously treated with
      multiple-dose insulin injections (MDII). METHODS: We undertook a retrospective
      analysis of five older patients (three women and two men) with type 1 diabetes
      and a mean age of 66.4 years (range, 57 to 76). The mean duration of disease was
      33 years (range, 18 to 49), and all patients had suboptimal glycemic control
      (glycosylated hemoglobin or HbA(1c) >8.0%), presence of microvascular
      complications, and unacceptably frequent hypoglycemia during MDII therapy. A
      diabetes care team monitored their clinical course after their treatment was
      changed to a CSII regimen. Data pertaining to HbA(1c), severe hypoglycemia, and
      insulin dose before and after conversion to CSII were compared with use of paired
      t tests. RESULTS: After initiation of CSII therapy, the mean HbA(1c) value
      decreased from 9.16% to 7.6% (P<0.0025), the rate of severe hypoglycemia
      decreased from 3.2 episodes to 0.4 episode per year (P<0.02), and the mean total
      daily insulin dose was reduced from 44.9 IU to 32.4 IU (P<0.05) during a mean
      duration of 12.6 months of CSII therapy. CONCLUSION: Insulin pump therapy can
      prove highly beneficial in older patients with type 1 diabetes by improving
      glycemic control, reducing hypoglycemic episodes and insulin dosage, and possibly
      increasing treatment satisfaction. These changes can potentially prevent
      morbidity and prove to be cost-effective. For implementation of pump conversion
      to be safe and successful, careful patient selection, proper education, and
      ongoing support through a comprehensive diabetes education and management program
      are imperative. Future reports of experience with CSII in elderly patients should
      help to elucidate its promising advantages in this patient population and provide
      guidelines for use.

PMID- 11585373
TI  - Meningioma metastatic to thyroid gland.
AB  - OBJECTIVE: To describe the first reported case of meningioma metastasizing to and
      completely infiltrating the thyroid gland. METHODS: We present a detailed case
      report, including radiographic, histologic, and immunostaining findings, in a
      patient with an atypical meningioma who had a progressively enlarging thyroid
      mass that proved to be a metastatic meningioma. RESULTS: A 49-year-old man had a
      meningioma in the parieto-occipital region that had spread locally to the scalp
      and bone by the time of surgical resection. Local recurrence during the following
      year prompted repeated surgical resection, tumor embolization, radiotherapy, and
      chemotherapy. Despite aggressive therapy, the tumor progressed. A thyroid mass
      was first noted 2 years after the meningioma was diagnosed. Enlargement of the
      mass caused airway obstruction, necessitating an emergency thyroidectomy.
      Histologic examination of the thyroidectomy specimen showed that the thyroid
      gland had been extensively replaced by metastatic meningioma. CONCLUSION: To our
      knowledge, this is the first reported case of metastatic meningioma extensively
      infiltrating the thyroid gland. This case report expands the spectrum of tumors
      that metastasize to the thyroid gland.

PMID- 11585374
TI  - Tertiary hyperparathyroidism after high-dose phosphate therapy in adult-onset
      hypophosphatemic osteomalacia.
AB  - OBJECTIVE: To describe a case of adult-onset hypophosphatemic osteomalacia
      treated with orally administered phosphate and complicated by tertiary
      hyperparathyroidism. METHODS: We present pertinent clinical, radiologic, and
      laboratory details of the study patient for a period of more than 20 years and
      discuss the few reported cases of tertiary hyperparathyroidism attributable to
      prolonged phosphate therapy. RESULTS: A 49-year-old Jordanian man, who had been
      diagnosed at age 26 years as having sporadic adult-onset hypophosphatemic vitamin
      D-resistant osteomalacia, presented with severe right hip pain, severe osteopenia
      with lytic bone lesions, and hypercalcemia after prolonged oral treatment with
      phosphate and vitamin D. These clinical, radiologic, and biochemical findings, in
      conjunction with a very high serum parathyroid hormone level, indicated the
      diagnosis of tertiary hyperparathyroidism, which was substantiated
      histopathologically. CONCLUSION: Physicians should be aware of the potential for
      development of tertiary hyperparathyroidism in patients receiving prolonged oral
      phosphate therapy.

PMID- 11585376
TI  - Hereditary gingival fibromatosis and growth retardation.
AB  - OBJECTIVE: To describe two patients with hereditary gingival fibromatosis (HGF)
      and growth hormone deficiency and to review the literature on HGF and related
      endocrine abnormalities. METHODS: We present case reports of two patients (first
      cousins)-an 8-year-old girl and a 13-year-old boy-with an existing diagnosis of
      HGF, who were assessed because of presumed growth failure. Both patients
      underwent growth hormone stimulation testing and more in-depth endocrine
      evaluation, including measurement of morning cortisol, adrenocorticotropic
      hormone (ACTH), and prolactin levels as well as thyroid function tests. An ACTH
      stimulation test was also performed. Radiologic evaluation included assessment of
      bone age and magnetic resonance imaging of the brain. RESULTS: In addition to
      HGF, both patients had short stature, subnormal growth velocity, and delayed bone
      age but no abnormalities on magnetic resonance imaging of the brain. Serum
      prolactin levels and results of thyroid function tests were normal. Subnormal
      growth hormone response was noted during hypoglycemia and pharmacologic stimuli
      with clonidine and levodopa. The female patient, who also had recurrent
      hypoglycemic episodes, had a suboptimal cortisol and ACTH response during
      hypoglycemia. On the ACTH stimulation test, she showed an inadequate cortisol
      response at 30 minutes but a normal response at 60 minutes. The male patient had
      normal morning cortisol and ACTH levels plus a normal response to ACTH
      stimulation. Both patients are responding well to treatment with growth hormone.
      The girl is also receiving cortisol replacement and has had no further episodes
      of hypoglycemia. CONCLUSION: Although HGF has been described as an isolated
      finding, it can occur as part of a syndrome, including infrequent endocrine
      abnormalities such as growth hormone insufficiency. The cause of the growth
      hormone deficiency remains unclear in these two patients. We believe that
      patients with HGF should be monitored carefully for a prolonged period for growth
      as well as other endocrine abnormalities.

PMID- 11585375
TI  - Unusual case of metastatic thyroid nodule: nonpalpable breast mass as origin.
AB  - OBJECTIVE: To document a case of thyroid cancer metastatic from the breast.
      METHODS: We present the clinical, laboratory, radiologic, and biopsy findings in
      our patient and review the related literature. RESULTS: A 47-year-old female
      patient was referred to our clinic because of dyspnea and generalized bone pain.
      Physical examination revealed a diffusely enlarged nodular goiter, and fine
      needle aspiration biopsy demonstrated intrathyroidal anaplastic cells. Total
      thyroidectomy was done, and the histopathologic diagnosis was anaplastic
      carcinoma. Unexpected rapid progression of the disease with cervical and
      intrathoracic lymphadenopathies and osteoblastic metastatic lesions without
      radioiodine uptake prompted us to attempt to rule out a primary nonthyroidal
      malignant lesion metastatic to the thyroid gland. The plasma level of CA 15-3 was
      profoundly increased (388 U/mL). Detailed reassessment of the patient disclosed a
      small mass in the right mammary gland with histopathologic features similar to
      those of the thyroidectomy material. Reevaluation of the thyroid specimens
      resulted in a final diagnosis of primary breast carcinoma in conjunction with
      metastatic carcinoma of the thyroid. CONCLUSION: Thorough systemic clinical
      assessment of a patient with a thyroid nodule and careful study of biopsy
      specimens should be done to ascertain whether the nodule is a primary or a
      metastatic lesion.

PMID- 11585377
TI  - Unusual case presentation of lichen simplex chronicus, Hodgkin's lymphoma, and
      nonpuerperal hyperprolactinemia-galactorrhea.
AB  - OBJECTIVE: To report the association of nonpuerperal galactorrhea and severe
      pruritus with clinical stage IIB Hodgkin's lymphoma. METHODS: We present a
      detailed history, findings on physical examination, laboratory data, and results
      of diagnostic imaging in a 25-year-old woman. A review of the related literature
      and speculations about possible etiologic factors for this association are
      provided. RESULTS: Dermatologic evaluation of the patient revealed lichen simplex
      chronicus with multiple excoriations on the anterior chest area and lower
      extremities. High serum prolactin concentrations and easily expressible
      galactorrhea were present. Magnetic resonance imaging of the sella with 1-mm
      cuts, however, revealed a normal pituitary gland. Computed tomography showed
      multiple enlarged mediastinal lymph nodes, and a left supraclavicular lymph node
      biopsy revealed the presence of Reed-Sternberg cells and lymphocyte alterations
      consistent with the diagnosis of Hodgkin's lymphoma. After one cycle of
      chemotherapy for management of the lymphoma, parallel reductions in serum
      prolactin concentrations and galactorrhea were noted. CONCLUSION: Possible causes
      for this syndrome include afferent mammary nerve stimulation resulting from
      scratching of pruritic skin and cytokine-induced hypersecretion of prolactin
      attributable to the lymphoma. Although uncommon, this syndrome may serve as an
      important harbinger of developing Hodgkin's lymphoma, and its disappearance may
      signify a therapeutic response.

PMID- 11585378
TI  - Lifestyle modifications in the prevention and treatment of hypertension.
AB  - OBJECTIVE: To present an objective, evidence-based review of the current
      literature on the role of lifestyle factors in hypertension. METHODS: We discuss
      the reported roles of obesity and overweight, nutritional factors, alcohol,
      physical activity, and smoking in the prevention and treatment of hypertension.
      RESULTS: For all age-groups and in both sexes, cross-sectional and prospective
      studies have shown a direct strong relationship between weight and blood
      pressure. In general, overweight is associated with a twofold to sixfold increase
      in the risk of developing hypertension. Clinical trials have proved that weight
      loss is effective in the primary prevention of hypertension as well as in the
      reduction of both systolic and diastolic blood pressure in patients with normal
      or high blood pressure. A decreased intake of dietary sodium has been
      demonstrated to have a hypotensive effect, both alone and as an adjunctive
      measure to pharmacologic therapy. Although no consensus currently exists about
      the role of potassium intake in prevention or control of hypertension, some
      studies support the protective value of high intake of potassium. A consistent
      relationship has been noted between consumption of alcohol and increased blood
      pressure, and reduced intake of alcohol has been shown to decrease blood pressure
      significantly. An inverse relationship exists between blood pressure and physical
      activity, independent of overweight or obesity. Moreover, increased physical
      activity helps lower both systolic and diastolic blood pressure. In a study of
      the effect of smoking and use of smokeless tobacco in healthy middle-aged men,
      ambulatory diastolic blood pressures were increased in both smokers and smokeless
      tobacco users in comparison with nonusers. CONCLUSION: Ample evidence supports
      the beneficial effects of healthful lifestyle modifications in the prevention and
      management of hypertension. Therefore, physicians should be motivated to provide
      guidance to the population relative to lifestyle practices that can help prevent
      and control hypertension.

PMID- 11585379
TI  - Diagnosis and procedure coding for bone mass measurement.
AB  - OBJECTIVE: To provide background information and practical advice about coding
      for submission of claims for reimbursement for performing bone mass measurement
      studies. METHODS: The current procedural terminology (CPT) codes for diagnoses
      and procedures related to reduced bone mass and osteoporosis are reviewed, and
      Medicare and other payer policies are discussed. RESULTS: Although considerable
      differences exist in payer policies relative to bone mass measurement, notable
      consistency is developing for Medicare patients. The CPT codes for pertinent
      outpatient and inpatient services, and applicable CPT modifiers, are outlined. In
      addition, examples are provided of criteria imposed for qualification for
      coverage. If a carrier or payer is not expected to provide coverage for the
      performance of a bone mass measurement study, an advance beneficiary notice
      (waiver statement) should be processed and the patient should be informed about
      the potential responsibility for payment before the test is done. CONCLUSION:
      Osteoporosis is an important and costly disorder that is rapidly increasing in
      prevalence in our society. Clinical endocrinologists have a critical role in the
      management of patients with this condition and an opportunity to contribute to
      high-quality care. Proper selection of patients for assessment and treatment and
      an understanding of certain restrictions and necessary documentation for
      insurance coverage may help obtain reimbursement for their care.

PMID- 11585380
TI  - Autoimmunity in "type 2" and gestational diabetes mellitus.

PMID- 11585381
TI  - Management of patients with osteoporosis.

PMID- 11585382
TI  - Production of proinflammatory cytokines by resident tissue macrophages after
      phagocytosis of apoptotic cells.
AB  - It is generally believed that apoptosis is not associated with inflammation.
      However, we have found that phagocytosis of apoptotic cells by PMA-treated THP-1
      cells and human monocyte-derived macrophages led to the production of
      proinflammatory cytokines, notably IL-8. These macrophages were obtained either
      by PMA treatment or by M-CSF treatment, possibly affecting the cytokine
      production after phagocytosis of apoptotic cells. In order to exclude the
      possibility, we employed resident tissue macrophages such as Kupffer cells and
      alveolar macrophages in this study and examined the production of cytokines after
      phagocytosis of apoptotic cells. Kupffer cells produced proinflammatory cytokines
      MIP-2 and TNF-alpha at the mRNA level. The MIP-2 protein was also detected by
      means of ELISA. Alveolar macrophages also produced the MIP-2 protein after
      phagocytosis of apoptotic cells. Furthermore, apoptotic thymocytes induced a
      similar response by these macrophages. These findings do support the notion that
      macrophages are apt to produce proinflammatory cytokines after phagocytosis of
      apoptotic cells.

PMID- 11585383
TI  - Human peripheral blood leukocyte engraftment into SCID mice: critical role of
      CD4(+) T cells.
AB  - We examined the influence of donor T lymphocytes on human peripheral blood
      leukocytes (PBL) engraftment into severe combined immune deficient (SCID) mice.
      Mice were injected with unfractionated or subset-depleted human PBL, and treated
      at various times with OKT3, a cytotoxic monoclonal antibody against human CD3(+)
      T lymphocytes. PBL engraftment, high levels of human Ig, and high incidence of
      lymphoproliferative disease (lpd) were found in mice transplanted with
      unfractionated PBL and CD8- or CD14-depleted PBL, and in mice treated with OKT3
      at distance from PBL transfer. Animals xenografted with CD3- or CD4-depleted PBL,
      or treated at transplantation time with OKT3, had very low levels of human Ig and
      did not develop lpd. PBL engraftment was minimal or absent in these animals, as
      determined by immunohistochemistry, dot-blot, and RT-PCR analyses. These results
      demonstrate that the presence of donor CD4(+) T lymphocytes at transplantation
      time is necessary for observing human PBL engraftment into SCID mice, an
      essential condition for human Ig production and lpd development.

PMID- 11585384
TI  - Cell cycle phase-specific survival of CD95 ligand-challenged Jurkat cells:
      upregulation of heat-shock response.
AB  - An important means of regulating T-cell function occurs via physical deletion
      (cytolysis) of unnecessary/unwanted T cells. Among cytolytic pathways, CD95 (Fas)
      based killing plays a prominent role. Although activation of T cells results in
      rapid upregulation of surface CD95 expression, sensitivity to CD95-based killing
      lags behind. To assess determinants of resistance to CD95-based killing, we used
      Jurkat cells as a model. Analysis of the 10% survivors of a LD(90) dose of CD95
      ligand (CD95L) at 24 h demonstrated them to arise preferentially from the S +
      G2/M phases of the cell cycle and to remain clustered in S + G2/M without
      undergoing cell division. Protein immunoblot, immunocytochemistry, and RT-PCR
      analyses demonstrated that hsp72 was markedly upregulated in CD95L survivors
      within hours of CD95L challenge, indicative of a heat-shock response. Indeed,
      exposure of Jurkat cells to bona fide heat shock did markedly upregulate hsp72
      and, upon subsequent CD95L challenge, did greatly enhance cell survival with
      persistent clustering to S + G2/M. These findings collectively suggest that in
      response to a CD95L insult, development of a heat-shock response above some
      critical threshold level can protect against lethality. This raises the
      possibility that exaggerated and/or protracted heat-shock responses under in vivo
      conditions may favor the survival of T cells (including autoaggressive T cells)
      that otherwise would be destined to die via a CD95-based pathway.

PMID- 11585385
TI  - Human leptin signaling in human peripheral blood mononuclear cells: activation of
      the JAK-STAT pathway.
AB  - Leptin is an adipocyte-secreted hormone that centrally regulates weight control.
      However, the leptin receptor is expressed not only in the central nervous system,
      but also in other systems, such as reproductive, hematopoietic, and immune
      tissues, suggesting various roles in addition to the regulation of food intake
      and energy expenditure. The leptin receptor bears homology to members of the
      class I cytokine receptor family. Leptin has previously been shown to enhance
      cytokine production by murine peritoneal macrophages and human circulating
      monocytes, where human leptin promotes activation and proliferation. We have
      recently found that the leptin receptor is expressed not only in monocytes but
      also in both CD4(+) and CD8(+) T lymphocytes. Besides, leptin enhances
      proliferation and activation of T lymphocytes when they are costimulated by PHA
      or Con A. In this paper, we have studied the signal transduction of the leptin
      receptor in peripheral blood mononuclear cells. We found that leptin stimulation
      activates the JAK-STAT signaling pathway. More specifically, we found that JAK
      2/3 and STAT-3 are activated by tyrosine phosphorylation upon leptin stimulation.
      Moreover, leptin stimulated tyrosine phosphorylation of the RNA binding protein
      Sam68 and its association with STAT-3. These effects were dose-dependent (0.1-10
      nM) and transient (5-30 min). We also observed the leptin stimulated
      translocation of activated STAT-3 from the cytoplasm to the nucleus. These
      results indicate that human leptin receptor in circulating mononuclear cells has
      the signaling capacity to activate JAK-STAT cascade. This pathway may mediate, at
      least in part, the action of human leptin in human peripheral blood mononuclear
      cells.

PMID- 11585386
TI  - Suppression of an IL-13 autocrine growth loop in a human Hodgkin/Reed-Sternberg
      tumor cell line by a novel IL-13 antagonist.
AB  - IL-13 has been proposed to be an autocrine growth factor for Hodgkin/Reed
      Sternberg tumor cells (H/RS cells). Since we have recently identified and
      produced a novel IL-13 antagonist (IL-13E13K) that can suppress the biological
      activity of IL-13, here we examined whether IL-13E13K can inhibit growth of
      Hodgkin lymphoma (HL)-derived cell lines. IL-13E13K not only inhibited the growth
      of an unstimulated H/RS cell line (L1236) but also cells that were stimulated by
      exogenous IL-13 in a dose-dependent manner. Several HL-derived cell lines
      expressed IL-13 message and protein and message for various chains of IL-13R.
      H/RS cell lines expressed mRNA for the IL-13R alpha 1, IL-4R alpha, and IL-2R
      gamma chains. However, none of these cell lines expressed the IL-13R alpha 2
      chain. An H/RS cell line (L1236) internalized the ligand-receptor complex after
      binding to a fusion protein composed of IL-13 and a mutated form of Pseudomonas
      exotoxin A (IL-13-PE38QQR, or IL-13 cytotoxin), as IL-13 cytotoxin was
      specifically cytotoxic to H/RS cells in vitro. These results indicate that IL
      13E13K and IL-13 cytotoxin can effectively suppress growth of a L1236 H/RS cell
      line. Therefore, additional studies should be performed to determine the
      expression of IL-13 and IL-13R in primary clinical samples of Hodgkin's lymphoma
      and both agents should be further tested in vitro and in vivo as possible
      therapeutic agents for HL.

PMID- 11585388
TI  - Interleukin-2 promotes antigenic reactivity of rested T cells but prolongs the
      postactivational refractory phase of activated T cells.
AB  - IL-2 is a principal autocrine growth factor that promotes T-cell activation and
      proliferation. However, IL-2 has also been implicated as a key intermediate in
      the induction and maintenance of self-tolerance in vivo. The purpose of this
      study was to assess whether the differential regulatory activity of IL-2 was
      related to the activation status of responder T cells. In cultures of rested
      myelin basic protein (MBP)-specific T cells, IL-2 not only induced IL-2R alpha
      but also augmented surface expression of several other activation-associated
      glycoproteins including OX40, LFA-1, B7.1, B7.2, TCR, and CD4. Pretreatment of T
      cells with IL-2 also up-regulated subsequent antigen reactivity in assays of MBP
      stimulated proliferation and IL-2 production and also promoted proliferative
      responsiveness to IL-2. In cultures of activated T cells, however, IL-2 inhibited
      subsequent reactivity to antigen or IL-2 and thereby prolonged a phase of
      postactivational refractoriness. Exposure of preactivated T cells to IL-2 also
      inhibited subsequent responses to the mitogenic combination of PMA, ionomycin,
      and IL-2 without enhancing cell death. These data support the concept that the
      inhibitory activity of IL-2 is dependent upon the activation status of T cells
      and is manifest as impaired cell cycle progression in response to a variety of IL
      2-dependent stimuli.

PMID- 11585387
TI  - Inflammation and lymphocyte activation during mycobacterial infection in the
      interferon-gamma-deficient mouse.
AB  - Interferon-gamma is a pivotal cytokine in the protective response to
      tuberculosis. In its absence rampant bacterial growth results in tissue
      destruction and death. While macrophage activation is key, this pleiotropic
      cytokine has other secondary but significant roles. To investigate these roles,
      both intravenous and aerosol infection of the IFN-gamma gene disrupted (GKO)
      mouse was performed. For the first time we describe the very similar growth of
      bacteria, during the initial phase of infection, between control and GKO mice.
      During this initial phase, however, very different histopathologic consequences
      between control and GKO mice were observed. Key observations included an early
      increased accumulation of granulocytes and a much more rapid and pronounced
      interstitial pneumonia in the GKO mice. As infection developed, GKO mice mounted
      an antigen-specific response; however, lymphocyte activation was much more rapid
      in these mice. Of interest is the fact that this increased rapidity occurred
      prior to significant differences in bacterial number. Taken together these data
      support a role for IFN-gamma in limiting both initial cellular recruitment and
      acquired lymphocytic responses to mycobacterial infection. This role may be key
      in surviving the kind of chronic stimulatory disease caused by Mycobacterium
      tuberculosis.

PMID- 11585389
TI  - Inappropriate expression of IgD from a transgene inhibits the function of antigen
      specific memory B cells.
AB  - IgD expression has been shown to be downmodulated upon mitogenic or antigenic
      activation of B cells. To investigate whether this decrease is of functional
      significance we studied a mouse strain that expresses transgenic IgD on all B
      cells. The rearranged gene encoding the heavy chain of this IgD requires
      endogenous gene rearrangement before it can be expressed; therefore, normal B
      cell development is not affected. As a result, both transgenic IgD and endogenous
      IgM and IgD are expressed on all peripheral B cells. We show that the presence of
      extraneous IgD does not affect normal B cell activation by polyclonal
      stimulators, nor does it affect the primary IgM or IgG responses to TI or TD
      antigens. However, the secondary memory response is significantly diminished. The
      decrease is not attributable to a defective generation of memory B cells; instead
      the activation of memory cells appears to be compromised. Since the depressed
      response can be overcome by prior aggregation of the transgenic IgD with allotype
      specific anti-IgD antibodies, it appears that persistence of the transgenic IgD
      on memory cells may influence their ability to be activated. Thus, the decrease
      in IgD expression on normal B cells after activation may be necessary for optimal
      activation of memory cells.

PMID- 11585390
TI  - Surface molecules essential for positive selection are retained but interfered in
      thymic epithelial cells after monolayer culture.
AB  - It has been reported that the three-dimensional structure of thymic epithelial
      cells (TECs) is responsible for thymic positive selection but that this ability
      disappears when TECs are cultured in monolayer. These results have supported the
      hypothesis that certain TEC-specific molecules are extinguished during monolayer
      culture. In this study, using MHC class II-restricted T-cell receptor transgenic
      mice, we demonstrated that preselected CD4(+)8(+) (DP) thymocytes were inhibited
      from developing into CD4(+)8(-) (CD4SP) cells in reaggregate thymus organ culture
      with monolayer-cultured TECs, but this inhibition was removed when TECs were
      cultured in monolayer with protein synthesis inhibitor or when the cultured TECs
      were treated with fixative. These results seem to be inconsistent with the
      previous hypothesis and indicate that monolayer culture allows TECs to retain the
      surface molecules necessary for positive selection but interferes with their
      function, which must be sustained for three dimensional structure.

PMID- 11585391
TI  - Computed tomography screening for lung cancer: back to basics.
AB  - After some years in the doldrums, interest in screening for lung cancer is
      resurging. Conflicting evidence from previous lung cancer screening trials, based
      on plain chest radiography, has been the subject of much debate: the failure to
      demonstrate a reduction in mortality has led to the widely held conclusion that
      screening for lung cancer is ineffective. The validity of this assumption has
      been questioned sporadically and a large study currently under way in the U.S.A.
      should help settle the issue. Recently, there has been interest in the use of
      computed tomography to screen for lung cancer; radiation doses have been reduced
      to 'acceptable' levels and the superiority of computed tomography (CT) over chest
      radiography for the identification of pulmonary nodules is unquestioned. However,
      whether improved nodule detection will result in a reduction in mortality has not
      yet been demonstrated. The present review provides a historical background to the
      current interest in low-dose CT screening, explains the arguments that previous
      studies have provoked, and discusses the recent and evolving status of lung
      cancer screening with CT. Ellis, S. M. et al. (2001).

PMID- 11585392
TI  - Dentascan in oral imaging.
AB  - In the past, dental disease and lesions involving the jaw were either evaluated
      by plain radiography or tomography. The advent of spiral computed tomography (CT)
      and DentaScan is changing the imaging trend. It is now not only used for pre
      implant assessment but also in the diagnosis of lesions affecting the jaw. This
      pictorial review discusses the role of DentaScan in the various abnormalities
      that may affect the mandible and maxilla.

PMID- 11585393
TI  - MRI contrast agents for evaluating focal hepatic lesions.
AB  - Contrast-enhanced magnetic resonance imaging (MRI) has become an important tool
      in the detection and characterization of focal hepatic lesions especially when
      other investigations such as ultrasound (US) and computed tomography (CT) are
      inconclusive. The purpose of this pictorial review is to briefly summarize the
      properties of various MRI contrast agents used in hepatic imaging and to
      highlight their role in evaluation of focal hepatic lesions.

PMID- 11585394
TI  - MRI of Creutzfeldt-Jakob disease: imaging features and recommended MRI protocol.
AB  - Creutzfeldt-Jakob Disease (CJD) is a rare, progressive and invariably fatal
      neurodegenerative disease characterized by specific histopathological features.
      Of the four subtypes of CJD described, the commonest is sporadic CJD (sCJD). More
      recently, a new clinically distinct form of the disease affecting younger
      patients, known as variant CJD (vCJD), has been identified, and this has been
      causally linked to the bovine spongiform encephalopathy (BSE) agent in cattle.
      Characteristic appearances on magnetic resonance imaging (MRI) have been
      identified in several forms of CJD; sCJD may be associated with high signal
      changes in the putamen and caudate head and vCJD is usually associated with
      hyperintensity of the pulvinar (posterior nuclei) of the thalamus. These
      appearances and other imaging features are described in this article. Using
      appropriate clinical and radiological criteria and tailored imaging protocols,
      MRI plays an important part in the in vivodiagnosis of this disease.

PMID- 11585395
TI  - Primary serous papillary carcinoma of the peritoneum: CT findings.
AB  - AIM: To describe the computed tomography (CT) findings of primary serous
      papillary carcinoma of the peritoneum. MATERIAL AND METHODS: The clinical data
      and imaging studies of 36 women aged 37-85 years with primary papillary serous
      carcinoma of the peritoneum were retrospectively evaluated. Twenty-seven patients
      presented with general abdominal complaints; all had elevated levels of CA-125.
      Thirty-two women were post-menopausal, four had had bilateral salpingo
      oophorectomy. RESULTS: The most common findings on pre-operative abdominal CT,
      performed in 30 patients, were a variable amount of ascites (n = 29), omental
      involvement (n = 28), irregular parietal peritoneum thickening (n = 22) and mural
      thickening of the sigmoid colon (n = 10). Thoracic findings included enlarged
      cardiophrenic nodes (n = 15) and pleural effusion (n = 11). Six patients had
      unilateral or bilateral adnexal masses of soft tissue density, which proved to be
      surface serous papillary carcinoma. CONCLUSION: Diffuse peritoneal disease on CT
      in patients with normal-sized ovaries or following bilateral salpingo
      oophorectomy, with elevated level of serum CA-125, but without an identifiable
      primary tumour, should suggest the diagnosis of primary serous papillary
      carcinoma of the peritoneum. Associated adnexal masses or focal bowel wall
      thickening may be seen, representing surface involvement by this tumour.

PMID- 11585396
TI  - Unilocular hepatic echinococcal cysts: sonography and computed tomography
      findings.
AB  - AIM: In endemic regions, unilocular hepatic echinococcal cysts (HEC) may be
      difficult to differentiate radiologically from simple non-parasitic cysts,
      especially if serological tests were negative. The aim of this descriptive study
      is to elucidate distinctive imaging findings that allow a diagnosis of HEC.
      MATERIALS AND METHODS: The sonographic and computed tomography (CT) findings of
      21 patients with proven unilocular HEC were retrospectively analysed. A total of
      28 examinations were reviewed, including 14 sonograms (ultrasound; US) of the
      liver and 14 CT studies. RESULTS: Seven imaging features that help in the
      diagnosis of unilocular HEC were identified by US and/or CT in 14 patients
      (14/21; 66.6%). They are, by order of frequency: hydatid sand (29.2%), focal or
      segmental thickening of the cyst wall (29.2%), coexistent echinococcal cysts in
      the spleen or lungs (16.6%), pericystic biliary radicles dilatation (8.3%),
      atrophy of the right lobe with compensatory hypertrophy of the left hepatic lobe
      (8.3%), satellite cysts typical of HEC in the liver (4.2%) and pericyst
      calcification (4.2%). CONCLUSION: These ancillary signs should prompt us to
      consider HEC as the cause of a unilocular cyst in approximately two-thirds of
      patients.

PMID- 11585397
TI  - Error review: can this improve reporting performance?
AB  - AIM: This study aimed to assess whether error review can improve radiologists'
      reporting performance. MATERIALS AND METHODS: Ten Consultant Radiologists
      reported 50 plain radiographs, in which the diagnoses were established. Eighteen
      of the radiographs were normal, 32 showed an abnormality. The radiologists were
      shown their errors and then re-reported the series of radiographs after an
      interval of 4-5 months. The accuracy of the reports to the established diagnoses
      was assessed. Chi-square test was used to calculate the difference between the
      viewings. RESULTS: On re-reporting the radiographs, seven radiologists improved
      their accuracy score, two had a lower score and one radiologist showed no score
      difference. Mean accuracy pre-education was 82.2%, (range 78-92%) and post
      education was 88%, (range 76-96%). Individually, two of the radiologists showed a
      statistically significant improvement post-education (P < 0.01,P < 0.05).
      Assessing the group as a whole, there was a trend for improvement post-education
      but this did not reach statistical significance. Assessing only the radiographs
      where errors were made on the initial viewing, for the group as a whole there was
      a 63% improvement post-education. CONCLUSION: We suggest that radiologists
      benefit from error review, although there was not a statistically significant
      improvement for the series of radiographs in total. This is partly explained by
      the fact that some radiologists gave incorrect responses post-education that had
      initially been correct, thus masking the effect of the educational intervention.

PMID- 11585398
TI  - Updated audit database for breast imaging/histopathology correlation.
AB  - AIM: To develop, test and validate an audit database, evolved from a prior, peer
      reviewed, audit tool for symptomatic multi-modality breast imaging services.
      MATERIALS AND METHODS: The database is to cover all aspects of non-invasive
      breast imaging and recognize subspeciality inputs. When more than one imaging
      investigation is used for diagnosis, an overall breast imaging audit grade is to
      be introduced. Data derived from clinical studies has been input into the new
      database. RESULTS: Results for mammography alone are virtually identical to those
      of the previous program. A slight increase in accuracy is suggested by using more
      investigations if the first investigation is not conclusive. More comprehensive
      reports can be issued. CONCLUSION: The audit program can be used in the same
      context as the old audit. If mammography is the sole investigation, there is no
      change from the previous standards of a minimum mammography
      (ultrasound)/histopathology agreement of 70%, an equivocal rate of less than 15%,
      a false-positive rate of less than 7.5% and a false-negative rate of less than
      6.5%. Although there is no statistical difference when more than one imaging
      investigation is used, there is some marginal improvement. It is suggested that
      initial audit standards for multi-imaging should be 75% for minimum agreement, a
      10% maximum for an equivocal rate, a 5% maximum for false negative and an
      unchanged false positive rate of 7.5% maximum. These standards will be refined
      with experience. Due to the nature of the database, complex queries can be made
      including those about histopathological data. If widely used, the database will
      be a useful tool to audit the accuracy of symptomatic breast imaging services and
      types and frequencies of symptomatic breast disease, as seen in routine settings.

PMID- 11585399
TI  - SPAMM, cine phase contrast imaging and fast spin-echo T2-weighted imaging in the
      study of intracranial cerebrospinal fluid (CSF) flow.
AB  - AIM: To compare the qualitative assessment of cerebrospinal fluid (CSF) flow
      using a SPAMM (spatial modulation of magnetization) technique with cine phase
      contrast images (cine PC) and fast spin echo (FSE) T2-weighted images. MATERIALS
      AND METHODS: SPAMM, PC and T2-weighted sequences were performed on 22 occasions
      in 19 patients. Eleven of the studies were performed following a neuroendoscopic
      third ventriculostomy (NTV), and in these cases, the success of the NTV was
      determined by clinical follow-up. Two observers used consensus to grade the
      presence of CSF flow at nine different sites for each study. RESULTS: At 14 of
      the 178 matched sites, which could be assessed by both SPAMM and cine PC, SPAMM
      CSF flow grade was higher than that of cine PC. At a further 14/178 matched
      sites, the cine PC grade was higher than that of SPAMM. There was definite CSF
      flow at 113/182 (62%) of all the cine PC sites assessed, and 110/181 (61%) of all
      SPAMM sites assessed whilst 108/198 (54%) of FSE T2-weighted image sites
      demonstrated flow voids. Cine PC grades were higher than SPAMM at the cerebral
      aqueduct (P < 0.05, Wilcoxon sign rank test). Definite CSF flow within the
      anterior third ventricle was present in 4/5 (SPAMM) and 3/5 (cine PC) successful
      NTVs, 0/2 (SPAMM and cine PC) unsuccessful NTVs and 1/10 (SPAMM and cine PC)
      patients without NTV. CONCLUSION: SPAMM provides a comparable assessment of
      intracranial CSF flow to that of cine phase contrast imaging at all CSF sites
      except the cerebral aqueduct.

PMID- 11585400
TI  - MRI appearance of synovial chondromatosis in the temporomandibular joint.

PMID- 11585401
TI  - Idiopathic metaplastic ossification of the breast.

PMID- 11585402
TI  - Retained myoma fragment after LASH procedure.

PMID- 11585403
TI  - Extraskeletal chondroma around the knee.

PMID- 11585404
TI  - Treatment of femoral artery pseudoaneurysms using percutaneous thrombin injection
      under ultrasound guidance alone-proceed with caution.

PMID- 11585405
TI  - Plain radiograph and renal tract ultrasound in the management of children with
      renal tract calculi.

PMID- 11585406
TI  - Stage III endometrial cancer: analysis of prognostic factors and failure patterns
      after adjuvant chemotherapy.
AB  - OBJECTIVE: This study was performed to assess the prognostic factors and patterns
      of recurrence in stage III endometrial carcinoma treated with surgery and
      adjuvant chemotherapy. METHODS: A retrospective review of 61 stage III
      endometrial carcinoma patients treated between 1988 and 1998 at Niigata
      University Hospital was performed. All patients underwent surgery, followed by
      adjuvant chemotherapy consisting of intravenous cisplatin, doxorubicin, and
      cyclophosphamide. Multivariate analysis was performed for the prognostic factors
      and actuarial techniques were used for the survival and recurrence rates.
      RESULTS: The 5-year disease-free survival was 78.6%. Multivariate analysis
      revealed deep myometrial invasion and lymph-vascular space involvement correlated
      significantly with disease-free survival. Based on these two factors, the
      patients could be divided into low-risk and high-risk groups. The 5-year disease
      free survival for the low-risk group was 100%, which was significantly better
      than the 59.1% for the high-risk group. Disease recurrence occurred in 13 of 30
      high-risk patients, and there was no recurrence in the 31 low-risk patients.
      Looking at the patterns of recurrence for the high-risk group by lymph node
      metastasis, 5 recurrences were locoregional, 1 was locoregional/distant, and 1
      was distant in 16 node-positive high-risk patients. In 14 node-negative patients,
      5 had distant and 1 had locoregional/distant recurrences. CONCLUSIONS: The
      locoregional failure in the node-positive high-risk group deserves further
      attention. For improvement of locoregional control, it may be worthwhile to
      consider new strategies. The role of new adjuvant chemotherapy should be
      investigated to control distant failure in node-negative high-risk patients.

PMID- 11585407
TI  - The significance of psammoma bodies on cervical cytology smears.
AB  - OBJECTIVE: The association between psammoma bodies on cervical smear (PBCS) and
      the presence of gynecological malignancy has been documented previously. The aim
      of this study was to determine the incidence of malignancy where psammoma bodies
      were detected on smear, to identify features that may be predictive of associated
      malignancy, and to make recommendations about management. METHODS: The databases
      of two large private pathology laboratories were accessed to obtain details of
      all patients reported to have PBCS between April 1992 and May 2000. A
      retrospective review was then undertaken to determine if any patients were found
      to have gynecological malignancies. The appearances of the background cells on
      the cervical smear and details of clinical management were recorded and
      evaluated. RESULTS: Twenty-two patients were found to have PBCS. Five patients
      were found to have a gynecological malignancy. These five patients were
      significantly older than the remaining patients. When these results were combined
      with all cases reported in the world literature, it became apparent that patients
      with coexisting malignancy were statistically significantly older than those not
      found to have malignancy (P < 0.0001). The cytological appearance of cells on the
      background smear was highly predictive of the presence or absence of malignancy.
      CONCLUSIONS: There is an association between PBCS and genital tract malignancy.
      This association is much stronger for postmenopausal women. The background
      cytology is highly predictive of the presence of associated malignancy. There is
      a strong argument that all women with psammoma bodies on cervical smear should
      undergo smear review, pelvic ultrasonography, hysteroscopy and biopsy, and
      laparoscopy to exclude the presence of a gynecological malignancy. For younger
      reproductive-aged women, a negative workup is reassuring.

PMID- 11585408
TI  - A longitudinal study on quality of life after gynecologic cancer treatment.
AB  - OBJECTIVE: The objective was to describe the pattern of quality of life (QOL)
      over time and to assess the impact of age, symptoms, disease parameters, and
      treatment on the overall QOL. METHODS: A longitudinal study on patients with
      newly diagnosed gynecologic cancer using individual patients as their own control
      was performed. The 33-item EORTC QLQ-C30(+3) was used as the QOL measure.
      Patients were assessed before treatment, after completion of treatment, and at 6,
      12, and 24 months. Spearman's correlation analyses were performed. A mixed effect
      model was fitted to the data. Bonferroni pairwise comparisons were used to
      analyze the different variables. RESULTS: One hundred forty-four women completed
      the study. Overall QOL improved after the completion of treatment but remained
      the same throughout the 2 years after treatment. The individual patient's QOL
      before treatment was insignificant while the impact of treatment on the
      individual patient was significant in determining QOL after treatment. There was
      a strong correlation for all time points in most factors, indicating that the
      global health status, functional scales, and symptom scales exhibit a dependent
      change over time. Relief in symptoms was associated with improvements in
      functional scales. The scores on overall QOL were lower for younger patients and
      for patients treated with chemotherapy than for patients treated with surgery.
      CONCLUSIONS: Strategies for supportive care need to focus on symptom management.
      Psychosocial interventions, to be effective, should include all patients and
      should aim to reduce the impact of treatment on the individual patient.

PMID- 11585409
TI  - May cathepsin D immunoreactivity be used as a prognostic factor in endometrial
      carcinomas? A comparative immunohistochemical study.
AB  - OBJECTIVE: To investigate the prognostic value of immunohistochemical detection
      of cathepsin D and the association between cathepsin D and established prognostic
      factors in endometrial carcinoma. METHODS: Cathepsin D immunoreactivity was
      determined by an immunohistochemical technique in a series of 79 patients with
      surgical stage I-III primary endometrial carcinoma. RESULTS: Of 79 tissue
      specimens, 48 (61%) showed a positive reaction for cathepsin D. A significant
      correlation between cathepsin D and histological grade was found (P < 0.05). The
      other established clinicopathological prognostic factors were not associated with
      cathepsin D. There was not any significant difference in prognosis between the
      positive cases and negative cases for cathepsin D (P > 0.05). In the univariate
      analysis cathepsin D immunoreactivity did not show significant prognostic value
      for overall survival (P > 0.05). The multivariate analysis also showed that
      cathepsin D was not related to patient outcome (P = 0.24, relative risk = 0.34,
      95% confidence interval = 0.05-2.09). CONCLUSIONS: Our results suggest that
      cathepsin D immunoreactivity may not be of prognostic value but more studies are
      needed to evaluate the relationship between its immunoreactivity in tumor cells
      and in other cells.

PMID- 11585410
TI  - Fatty acid composition of lysophosphatidic acid and lysophosphatidylinositol in
      plasma from patients with ovarian cancer and other gynecological diseases.
AB  - OBJECTIVE: We previously reported that plasma levels of total lysophosphatidic
      acid (LPA) represented a potential biomarker for ovarian cancer and other
      gynecological cancers [1]. However, total LPA is composed of different LPA
      species with distinct fatty acid chains. The major objective of the current
      study, therefore, was to determine whether one or more specific fatty acid LPA
      species was associated with disease or disease staging. If this was determined,
      these species could be useful in further improving the sensitivity and/or
      specificity of this biomarker for the diagnosis and/or prognosis of the disease.
      Because lysophosphatidylinositol (LPI) co-migrates with LPA, this study
      represents the analysis of combined molecular species from both lysolipid
      classes. METHODS: The patient population, sample collection, and analyses have
      been reported previously [1]. Lipids were hydrolyzed from the LPA band on thin
      layer chromatography plates. The following individual fatty acid species were
      analyzed by gas chromatography: palmitic acid (16:0), stearic acid (18:0), oleic
      acid (18:1), linoleic acid (18:2), arachidonic acid (20:4), and docosahexaenoic
      acid (22:6). The LPA/LPI fatty acid composition levels were analyzed and compared
      with disease status. RESULTS: Distinct plasma LPA/LPI fatty acid chain species
      were not associated with ovarian or other gynecological cancers, compared to
      patients with benign gynecological disease or healthy controls. However, an
      increased presence of unsaturated fatty acids in plasma LPA/LPI was found in
      patients with late-stage or recurrent ovarian cancer and possibly with other
      gynecological cancers. CONCLUSIONS: Analysis of individual fatty acid species
      present in plasma LPA/LPI do not appear to enhance the sensitivity or specificity
      of total LPA/LPI as a marker for gynecological cancer detection. However, our
      results suggest that increased LPA/LPI species with unsaturated fatty acid chains
      may be associated with late-stage or recurrent ovarian cancer.

PMID- 11585411
TI  - Production of activin A in hyperplasia and adenocarcinoma of the human
      endometrium.
AB  - OBJECTIVES: To examine the possible localization and production of activin A in
      human normal endometrium, endometrial hyperplasia, and adenocarcinoma tissues.
      METHODS: Human endometrial tissues were collected from 45 patients who were
      undergoing abdominal hysterectomy. Tissue sections were stained with monoclonal
      antibodies against the inhibin/activin alpha- and beta A-subunits and activin A
      using an avidin-biotin-peroxidase complex technique. Concentrations of activin A
      and inhibin A in tissue extracts of the endometrial tissues were measured using
      enzyme-linked immunosorbent assays (ELISAs). The expressions of the inhibin alpha
      subunit and activin beta A-subunit messenger RNA (mRNA) in the endometrial
      tissues were demonstrated by reverse transcription-polymerase chain reaction (RT
      PCR) analysis. RESULTS: No immunostaining with an antibody against the inhibin
      alpha-subunit was observed in human normal endometrium, endometrial hyperplasia,
      and adenocarcinoma. By contrast, immunostaining for the activin beta A-subunit
      and activin A was observed in the cytoplasm of glandular cells in normal
      endometrium, endometrial hyperplasia, and tumor cells of endometrial
      adenocarcinoma. The percentages of stained cells in endometrial adenocarcinoma
      were higher than those in normal endometrium. Also, the percentages of stained
      tumor cells with poor differentiation were higher than those with good and
      moderate differentiation of the endometrium. The stromal cells in normal
      endometrium, endometrial hyperplasia, and adenocarcinoma were weakly
      immunoreactive with antibodies against the beta A-subunit and activin A.
      Immunoreactivity of activin A in tissue extracts from normal endometrium and
      endometrial adenocarcinoma was detected by the two-site ELISA. Immunoreactivity
      of activin A was significantly higher in adenocarcinoma than in normal
      endometrium. On the other hand, the immunoreactive inhibin A was not detected.
      The expression of the alpha-subunit mRNA in endometrial tissues was demonstrated
      as the RT-PCR products migrated at 905 bp and the PCR products of the beta A
      subunit showed a band at 366 bp. CONCLUSIONS: It is suggested that activin A, but
      not inhibins, are produced by endometrial tissues. The amounts of produced
      activin A were higher in adenocarcinoma tissues than in normal endometrium.
      Activin A might be involved in human endometrial tumorigenesis.

PMID- 11585412
TI  - Complete surgical cytoreduction of advanced ovarian carcinoma using the argon
      beam coagulator.
AB  - OBJECTIVE: The aim of this study was to evaluate the utility of the argon beam
      coagulator (ABC) in achieving optimal (< or =1 cm) disease status and
      facilitating the conversion of optimal but visible disease (0.1-1.0 cm) to
      microscopic residual disease (complete cytoreduction) among patients with
      advanced ovarian carcinoma. METHODS: All patients undergoing their primary
      attempt at surgical cytoreduction for Stage IIIB-IV epithelial ovarian carcinoma
      between October 1, 1997 and June 30, 2000 were identified from the tumor registry
      database. Data were abstracted retrospectively and included: the size/location of
      precytoreduction disease, surgical procedures performed, the anatomic regions in
      which the ABC was used for cytoreduction, the size/location of residual tumor,
      and the date of last follow-up and disease status. Survival curves were generated
      using the Kaplan-Meier method, and statistical comparisons were performed using
      the chi(2) test, Fisher's exact test, log rank test, and multivariate logistic
      regression. RESULTS: Forty-five patients were identified (FIGO Stage IIIB = 8,
      Stage IIIC = 29, Stage IV = 8). Overall, optimal cytoreduction was achieved in
      84.4% of patients; 60.0% had only microscopic residual and 24.4% had residual
      disease 0.1-1.0 cm. The ABC was used to facilitate cytoreduction in 31 patients.
      Optimal disease status was achieved in 93.6% of cases in which the ABC was used
      compared with 64.3% for non-ABC cases (P < 0.023). ABC use was also associated
      with a higher rate of complete cytoreduction (74.2%) compared with non-ABC cases
      (28.6%, P < 0.004). Among patients left with optimal disease (< or =1 cm),
      conversion to only microscopic residual was achieved in 79.3% of cases using the
      ABC and 44.4% of cases without ABC use (P < 0.044). The ABC was associated with a
      statistically significantly higher rate of complete cytoreduction for disease
      located in the lesser sac/gastrocolic ligament (90.9% vs 14.3%), abdominal
      peritoneum (95.5% vs 50.0%), bowel mesentery (80.0% vs 0), and pelvis (89.3% vs
      50.0%). Multivariate analysis revealed that use of the ABC (P = 0.006) and
      disease in three or fewer anatomic regions (P = 0.014) were independent
      predictors of a microscopic residual surgical outcome. Complete cytoreduction was
      associated with a significant advantage in median progression-free survival (22.2
      months) compared with patients with optimal but visible (0.1-1.0 cm) residual
      disease (12.3 months) and those with suboptimal (>1.0 cm) residual disease (6.3
      months, P < 0.001). Among ABC cases, the mean estimated blood loss was 527 ml,
      and major postoperative complications occurred in 9.7% of patients. CONCLUSIONS:
      The ABC is a useful adjunct to conventional tumor reductive techniques and
      appears to significantly increase the feasibility of achieving both optimal
      disease status and complete cytoreduction of all visible tumor in patients with
      macroscopic metastatic ovarian carcinoma.

PMID- 11585413
TI  - Ablation of metastatic ovarian carcinoma with the argon beam coagulator:
      pathologic analysis of tumor destruction.
AB  - OBJECTIVE: The aim of this study was to characterize the histopathologic effects
      of electrosurgical tumor destruction of metastatic ovarian carcinoma using the
      argon beam coagulator (ABC) and evaluate the depth of tissue damage produced by a
      range of power settings and tissue interaction times. METHODS: Epithelial ovarian
      carcinoma tumor specimens (1 cm(3)) were harvested intraoperatively. Following
      surgical excision, electrosurgical destruction of tumor was effected using the
      ABC at three power settings (60, 80, and 100 W) and three tissue interaction time
      intervals (1, 3, and 5 s), yielding nine experimental groups of 16 samples each
      (n = 144). Samples were formalin-fixed, cross-sectioned, stained with hematoxylin
      and eosin, and examined microscopically for histologic characteristics and depth
      of tissue destruction. RESULTS: Microscopic evaluation revealed that the total
      depth of destruction (TDD) produced by the ABC was composed of three distinct
      zones of tissue injury: vaporization, carbonized eschar (ESC), and coagulative
      necrosis (NEC). For each power setting, the mean TDD increased in a linear
      fashion as the interaction time interval increased from 1 to 5 s (60 W, 1.71 to
      2.43 mm; 80 W, 2.24 to 3.69 mm; 100 W, 3.21 to 5.58 mm). By regression analysis,
      both power setting and tissue interaction time were independently associated with
      increasing TDD, with power having the strongest effect. At all power settings and
      interaction time intervals, the incremental change in TDD was primarily a
      function of the degree of tissue vaporization, which increased from 0.59 mm at 60
      W (1 s) to 3.22 mm at 100 W (5 s). For all experimental groups, the ratio of
      NEC/ESC was highly consistent, ranging from 1.03 to 1.33 (P > 0.05, Bonferroni
      multiple comparisons procedure), and demonstrated that for each resulting ESC, an
      equivalent or greater degree of underlying NEC was also present. CONCLUSIONS: The
      destruction of ovarian carcinoma tumor tissue produced by the ABC is dependent
      upon both power setting and tissue interaction time. Increasing depth of
      destruction is due predominantly to a deeper level of tissue vaporization. The
      NEC/ESC ratio provides a reliable means of estimating the true depth of tumor
      destruction produced by the ABC and may contribute to increased safety and
      efficacy of electrosurgical cytoreduction of using this technique.

PMID- 11585415
TI  - Trends in the mortality (1950-1997) and incidence (1975-1993) of malignant
      ovarian neoplasm among Japanese women: analyses by age, time, and birth cohort.
AB  - OBJECTIVE: The purpose of this study was to explore epidemiological features of
      malignant ovarian neoplasm in Japan. METHODS: The number of deaths from malignant
      ovarian neoplasm was obtained from the national vital statistics. Estimated
      incidence rates, based on several cancer registries, were also used for analyses.
      We divided the subjects into two age groups (0-29 and 30+ years) and examined
      secular trends in mortality (1950-1997) and incidence (1975-1993) by age, time,
      and birth cohort. RESULTS: The age-adjusted mortality rate has increased
      approximately 4-fold (from 0.9 to 3.6 per 100,000 women) from 1950 to 1997. Age
      specific mortality rates showed a rising pattern in the elderly, whereas
      mortality in the younger people tended to increase in the 1950s and 1960s, but
      then decreased in the 1970s and afterward. In analyses using a mathematical
      model, the time effect in the population aged 0-29 years increased with advancing
      period up to 1970, and then decreased. The cohort effects had positive values,
      which indicate higher than additive influence from age/time effect, for birth
      cohorts from 1900 to 1935. The age-adjusted incidence rate increased
      approximately 1.5-fold (from 3.6 to 5.7) from 1975 to 1993. The rate increased in
      the early 1980s, but has remained stable since the late 1980s. Age-specific
      incidence rates in older age groups increased steadily up to 1985, and have
      remained stable since, while the rates in younger women have remained almost
      unchanged. CONCLUSION: The major effects on malignant ovarian neoplasm in Japan
      are supposed to be due to declining parity and therapeutic improvements.

PMID- 11585414
TI  - Implication of malignancy and prognosis of p27(kip1), Cyclin E, and Cdk2
      expression in epithelial ovarian tumors.
AB  - OBJECTIVE: The aim of this study was to further evaluate whether the expression
      of p27(kip1), cyclin E, and cdk2 is related to the malignancy of ovarian tumors
      and whether their expressions, alone or in combination, are associated with
      prognosis in epithelial ovarian carcinoma. METHODS: Immunohistochemical analysis
      using anti-p27(kip1), anti-cyclinE, and anti-cdk2 antibodies was carried out for
      103 cases consisting of benign, borderline, and malignant ovarian tumors, and
      Western blot analysis and cdk2 activity assay were performed in 26 fresh ovarian
      tumor samples. RESULTS: p27(kip1) expression was reduced in ovarian carcinomas in
      contrast to benign and borderline tumors. The expression of cyclin E and cdk2
      gradually increased from benign to borderline to malignant tumors. Kaplan-Meier
      survival analysis showed that patients with p27(kip1) expression had a high
      overall survival rate. Patients with cyclin E overexpression had a low overall
      survival rate. When the combination of these proteins was analyzed, patients with
      the p27(kip1) (-)/cyclin E (++)/cdk2 (++) phenotype were significantly associated
      with the poorest overall survival. In multivariate Cox regression analysis, the
      combined phenotype of p27(kip1) (-)/cyclin E (++)/cdk2 (++) was independently
      related to poor prognosis. CONCLUSIONS: Our results suggest that loss of
      p27(kip1) expression and overexpression of cyclin E or cdk2 were significantly
      associated with malignancy in ovarian tumors. p27(kip1) and cyclin E proteins may
      be valuable prognostic factors for epithelial ovarian carcinoma patients.
      Furthermore, the combined evaluation of p27(kip1)/cyclin E/cdk2 may provide the
      most important prognostic implication.

PMID- 11585416
TI  - Role of wide/radical hysterectomy and pelvic lymph node dissection in endometrial
      cancer with cervical involvement.
AB  - OBJECTIVE: The goal of this work was to assess retrospectively the role of
      wide/radical hysterectomy (RH) and pelvic lymph node dissection (LND) in
      endometrial cancer with cervical involvement. METHODS; From 1984 to 1993, 82
      patients with endometrial cancer and cervical involvement were surgically managed
      at our institution. Of 57 patients with stage II (59%) or III (41%) disease
      receiving no preoperative therapy, 22 (39%) had simple hysterectomy (SH) and 35
      (61%) had RH. Forty-four patients (77%) had pelvic LND, and 38 (67%) had adjuvant
      radiotherapy (RT). Median follow-up was 70 months. RESULTS: The 5-year disease
      related survival (DRS) and recurrence-free survival (RFS) were 73 and 63%,
      respectively. Five-year DRS and RFS were 68 and 50%, respectively, in the SH
      group compared with 76% (P = 0.1) and 71% (P = 0.04) in the RH group. Distant
      recurrences occurred in 45% of patients with SH and in 23% with RH (P = 0.08).
      Local recurrence rates did not differ significantly. Considering only stage II
      tumors, we did not observe any recurrence among patients with negative nodes who
      had RH, irrespective of the administration of adjuvant RT. By contrast, adjuvant
      RT improved local control (even if not significantly) in stage II patients who
      had SH. Five-year DRS of stage III patients was 47%, but it was improved by
      adjuvant RT in the subgroup of patients who had RH. Independent variables
      associated with prognosis were stage III disease, deep myometrial invasion, RH,
      and adjuvant RT. CONCLUSION: RH and adjuvant RT appear to improve prognosis in
      endometrial cancer with cervical involvement. In particular, radical surgery
      alone is therapeutic in stage II patients with negative nodes, irrespective of
      the administration of RT. By contrast, RT can possibly improve local control in
      stage II patients who previously had SH. Overall, stage III patients have a poor
      prognosis that can be improved by a combination of radical surgery and adjuvant
      RT; however, associated therapy directed to extrapelvic sites is probably needed
      in patients with extrauterine disease.

PMID- 11585417
TI  - Somatic mutations of the PTEN/NMAC1 gene associated with frequent chromosomal
      loss detected using comparative genomic hybridization in endometrial cancer.
AB  - OBJECTIVES: We analyzed the mutational status of the transforming growth factor
      beta type II receptor (TGF beta RII), BAX, and PTEN/MMAC1 genes as well as
      microsatellite instability (MI) in 29 consecutive cases of endometrial carcinoma
      operated on at the Cancer Institute Hospital (Tokyo, Japan). To identify
      chromosomal loss associated with significant somatic mutations, we conducted
      comparative genomic hybridization (CGH) analysis. METHODS: We conducted a direct
      sequence for mutational analysis of these genes. To examine copy number loss at
      the chromosomal regions bearing these genes, we used CGH analysis. CGH analysis
      may provides a genome-wide overview about tumor-associated genomic imbalances.
      RESULTS: Among nine tumors that showed the MI+ phenotype, four (44%) demonstrated
      a significant mutation with a definite amino acid change in the PTEN/MMAC1 gene.
      CGH analysis demonstrated that all four tumors (100%) showed chromosomal copy
      number loss around the locus of this gene, whereas four (57%) of seven tumors
      with PTEN/MMAC1 mutations showed chromosomal loss or double mutations in MI-
      carcinomas. The role of TGF beta RII and BAX genes is limited as a target gene of
      MI+ phenotype in endometrial cancer, because several mutations of these genes
      were detected but a chromosomal loss was demonstrated by CGH in only one tumor in
      MI+ endometrial cancers with mutation. CONCLUSIONS: This report reveals, by using
      CGH, that most MI+ endometrial cancers with PTEN/MMAC1 mutations as well as MI-
      tumors showed inactivation of both alleles of this gene, which strongly suggested
      the involvement of this gene in carcinogenesis.

PMID- 11585418
TI  - Uterine adenosarcoma with sarcomatous overgrowth versus uterine carcinosarcoma:
      comparison of treatment and survival.
AB  - OBJECTIVE: Uterine adenosarcoma with sarcomatous overgrowth (ASSO) is a rare
      variant of uterine sarcoma first described in 1989. This clinicopathologic study
      was undertaken to compare the treatment and survival of uterine adenosarcoma with
      sarcomatous overgrowth to that of uterine carcinosarcomas. METHODS: A review of
      uterine sarcomas diagnosed at Washington Hospital Center from January 1988 to
      December 1998 was performed. Records were reviewed for demographic data, surgical
      staging, primary and adjuvant therapy, metastatic site, disease recurrence, and
      survival. All pathology was reviewed and diagnosis confirmed. Statistical
      analysis included chi(2) test and Student's t test. Kaplan-Meier survival curves
      were plotted to estimate the median and 5-year survival times. The log-rank test
      was used to compare survival times. A P value <0.05 was considered significant.
      RESULTS: Sixty patients were diagnosed with uterine sarcoma at Washington
      Hospital Center. Of these, 33 (55%) were uterine carcinosarcomas, 11 (18%) ASSOs,
      6 (10%) adenosarcomas, and 10 (17%) leiomyosarcomas. Of the patients diagnosed
      with uterine ASSO, 3 (27%) were stage I, 3 (27%) stage II, 1 (9%) stage III, and
      4 (36%) stage IV. All 11 patients with uterine ASSO underwent total abdominal
      hysterectomy with bilateral salpingo-oophorectomy and tumor debulking.
      Postoperative adjuvant therapy included chemotherapy (n = 4), radiation (n = 4),
      combination radiation and chemotherapy (n = 1), and no adjuvant therapy (n = 2).
      The overall median survival time of patients with uterine ASSO was 13 months.
      Nine of eleven patients are dead of disease, and two patients (both with stage I)
      are alive without evidence of disease at 18 and 19 months. Thirty-three patients
      with carcinosarcoma were identified, with follow-up available on 29 patients. Of
      these, 10 (34%) were stage I, 6 (22%) stage II, 3 (10%) stage III, and 10 (34%)
      stage IV. Twenty-seven of the twenty-nine patients diagnosed with carcinosarcoma
      underwent surgical therapy to include total abdominal hysterectomy, bilateral
      salpingo-oophorectomy, staging and tumor debulking. Two patients died prior to
      treatment. Postoperative adjuvant therapy included chemotherapy (n = 9),
      radiation (n = 13), combination (n = 1), and no further therapy (n = 4). Twenty
      of the twenty-nine patients are dead of disease; there were nine surviving
      patients at the time of this report (stage I-5, stage II-3, stage III-1). The
      median survival of these patients was 31 months, with an overall 5-year survival
      of 22%. Comparison of the Kaplan-Meier survival curves using the log-rank test
      suggests a worse prognosis for uterine ASSO. However, this did not reach
      statistical significance (P = 0.0522). CONCLUSIONS: Patients diagnosed with
      uterine ASSO have a poor prognosis similar to that of carcinosarcoma. Management
      should include complete surgical staging. Additional therapy in the form of
      radiation, chemotherapy, or both has been reported; however, the superiority of
      one modality could not be determined from our data.

PMID- 11585419
TI  - The significance of human papillomavirus viral load in prediction of histologic
      severity and size of squamous intraepithelial lesions of uterine cervix.
AB  - OBJECTIVES: Persistence of high-risk types of human papillomavirus (HPV) in
      cervical scrapes is responsible for the development, maintenance, and progression
      of squamous intraepithelial lesions (SILs). Previous studies of viral load and
      histologic severity have ended with controversial results. This study evaluated
      the relationships of HPV viral load with size and histologic severity of cervical
      lesions, which has not been reported previously. METHODS: By using Hybrid Capture
      II, DNA level of high-risk HPVs was determined in cervical scrapes and correlated
      with lesion size and histologic confirmation for 73 women referred for
      colposcopy. The lesion size was classified as nonvisible (n = 12), small (< or
      =2/5 of the 12x colposcopic visual filed, n = 36), and large (>2/5 of the 12x
      field, n = 25) lesions. The final disease status was categorized as high-grade
      SIL (HSIL)/squamous cell carcinoma (SCC) (designated HSIL+) (n = 32), low-grade
      SIL (LSIL) (n = 19), and no detectable SIL (n = 22). RESULTS: A distinct upward
      trend of high-risk HPV DNA levels paralleled increasing size and histologic
      severity of cervical lesions (P = 0.003 and 0.001, respectively). With respect to
      relative risk, women who had high viral load of HPV were at significantly greater
      risk for large lesion size (odds ratio [OR] = 5.3, 95% confidence interval [CI] =
      1.1-24.9) and HSIL+ (OR = 35.0, 95% CI = 4.2-294.5). Of particular note, the risk
      of developing large lesion size and HSIL+ significantly increased with increasing
      viral load of HPV (P values for trend test were 0.008 and 0.0004, respectively).
      In contrast, there were no significant associations of trend in viral load with
      risk in small lesion size and LSIL. CONCLUSIONS: The present study revealed that
      the effect of HPV infection on SIL development is highly influenced by high viral
      load and highlighted a potential application of viral load testing in predicting
      the size and severity of lesions of the uterine cervix.

PMID- 11585420
TI  - Endometriosis-associated ovarian carcinoma (EAOC): an entity distinct from other
      ovarian carcinomas as suggested by a nested case-control study.
AB  - OBJECTIVES: Endometriosis-associated ovarian carcinoma (EAOC) has recently
      received increasing attention due to its suggested biological behavior,
      distinctive from those of usual epithelial ovarian cancer. To elucidate some of
      the controversies on this intriguing entity, a series of patients with EAOC were
      compared to ovarian carcinoma cases without concomitant endometriosis. METHODS:
      To control the confounding effect of age, a nested case-control study was
      designed, where all 58 EAOC patients (mean age 54.5 +/- 11.5 years) were nested
      with four perfectly age-matched non-EAOC patients (n = 232; mean age 54.7 +/-
      11.7 years) selected among 425 women representing all FIGO stages of ovarian
      carcinomas without endometriosis. Pertinent clinical data and results of analysis
      of the tumors were subjected to statistical analyses using life-table, univariate
      (Kaplan-Meier), and multivariate (Cox) survival techniques to disclose
      dissimilarities in the key biological characteristics of these two groups as well
      as the independent prognostic predictors of disease outcome. RESULTS: When
      compared in a case-control design with four perfectly age-matched non-EAOC
      patients nested to each EAOC case, the patients with EAOC proved to: (1) have a
      lower stage disease (both FIGO and TNM) (P = 0.000), (2) show a completely
      different distribution of histological subtypes (significant overpresentation of
      endometrioid and clear cell carcinomas) (P = 0.0001), (3) have predominantly
      lower grade lesions (P = 0.029), (4) be devoid of any primary residual tumor (P =
      0.0001), and, most importantly (5) have demonstrated a significantly better
      overall survival (47/58 versus 126/232; OR 2.89, 95% CI 1.56-5.34, P = 0.0001).
      This better survival was evident (a) in all age groups and (b) for all
      histological subtypes, but (c) not explained by a better stage-specific survival
      in any FIGO stage. The two series also differed in their significant prognostic
      predictors in Kaplan-Meier and Cox analyses. In the EAOC group, the most
      significant (P = 0.0001) predictors of OS in univariate analysis were age,
      histological type, observation time for endometriosis, and distribution of
      endometriosis. In the non-EAOC group, such significant predictors were age,
      residual tumor, and type of therapy. In the multivariate (Cox) model, age and
      FIGO stage were the only two significant independent prognostic factors shared by
      these two series. In addition, histological type and type of therapy proved to be
      significant independent predictors in the non-EAOC series. CONCLUSIONS: These
      data suggest that EAOC deviates from the non-EAOC in many of its key biological
      characteristics. The implications of these data in the diagnosis, treatment
      policy, and prognostication still require confirmation by further studies,
      however.

PMID- 11585421
TI  - Survival of BRCA1 negative ovarian cancer patients based on family history.
AB  - OBJECTIVE: To compare survival of ovarian cancer patients with and without a
      family history of breast or ovarian cancer who are known to be without mutations
      in BRCA1. METHODS: Patients with ovarian cancer were tested for germline
      mutations in BRCA1 by polymerase chain reaction amplification of DNA for single
      strand conformation polymorphism and direct sequencing analysis to examine the 22
      coding exons of BRCA1 in fresh and archived tumor specimens. Demographic and
      survival data were collected for statistical analysis. Survival data were
      calculated by the method of Kaplan and Meier and compared by the log-rank test.
      RESULTS: Of the 110 patients tested at our institution, 100 were noted to be
      negative for BRCA1 mutations. After exclusion of nonepithelial histologies,
      benign tumors, primary peritoneal carcinoma, and incomplete staging, 87 patients
      remained for analysis, of which 37 demonstrated a family history of breast or
      ovarian cancer. The two groups showed similar age at diagnosis, stage, grade,
      residual disease, and type of chemotherapy. Median actuarial survival was 75
      months for those patients with a family history versus 70 months for those
      without (P = 0.73). Evaluation of patients with two or more relatives with breast
      or ovarian cancer also revealed no differences in survival. CONCLUSIONS: Family
      history of breast or ovarian cancer does not affect survival of patients with
      ovarian cancer in the absence of mutations in BRCA1. Previously described
      differences in survival among patients with BRCA1 mutations may be more related
      to genetic factors than to biases introduced by the presence of family history.

PMID- 11585422
TI  - Safety and efficacy of low anterior en bloc resection as part of cytoreductive
      surgery for patients with ovarian cancer.
AB  - OBJECTIVE: To examine the feasibility and safety of a low anterior resection of
      the rectosigmoid plus adjacent pelvic tumour as part of primary cytoreduction for
      ovarian cancer. METHODS: This study included 65 consecutive patients with primary
      ovarian cancer who had debulking surgery from 1996 through 2000. All patients
      underwent an en bloc resection of ovarian cancer and a rectosigmoid resection
      followed by an end-to-end anastomosis. Parameters for safety and efficacy were
      considered as primary statistical endpoints for the aim of this analysis.
      RESULTS: Postoperative residual tumour was nil, <1 cm, and >1 cm in 14, 34, and
      14 patients, respectively. The median postoperative hospital stay was 11 days
      (range, 6 to 50 days). Intraoperative complications included an injury to the
      urinary bladder in one patient. Postoperative complications included wound
      complications (n = 14, 21.5%), septicemia (n = 9, 13.8%), cardiac complications
      (n = 7, 10.8%), thromboembolic complications (n = 5, 7.7%), ileus (n = 2, 3.1%),
      anastomotic leak (n = 2, 3.1%), and fistula (n = 1, 1.5%). Reasons for a
      reoperation during the same admission included repair of an anastomotic leak (n =
      1), postoperative hemorrhage (n = 1), and wound debridement (n = 1). Wound
      complications, septicemia, and anastomotic leak formation were more frequent in
      patients who had a serum albumin level of < or =30 g/L preoperatively. There was
      one surgically related mortality in a patient who died from a cerebral vascular
      accident 2 days postoperatively. CONCLUSIONS: An en bloc resection as part of
      primary cytoreductive surgery for ovarian cancer is effective and its morbidity
      is acceptably low.

PMID- 11585423
TI  - Altered mRNA expression of sialyltransferase in squamous cell carcinomas of the
      cervix.
AB  - OBJECTIVE: Increased sialylation has been reported in various kinds of cancers,
      but to date, sialylation of cervical carcinoma has never been evaluated. This
      study of the changes in messenger ribonucleic acid (mRNA) expression of the four
      sialyltransferases (ST3Gal I, ST3Gal III, ST3Gal IV, and ST6Gal I) in a normal
      cervix and that with FIGO stage IB1 squamous cell carcinoma was undertaken to
      assess the extent of sialylation associated with establishment of the carcinoma.
      METHODS: Alterations in ST mRNA expression in FIGO IB1 cervical cancer (n = 30)
      and normal cervixes (n = 30) were examined by semiquantitative reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: ST6Gal I expression
      was enhanced in squamous cell carcinoma of the cervix (P = 0.026, Mann-Whitney U
      test), but mRNA expression from the other three STs (ST3Gal I, ST3Gal III, and
      ST3Gal IV) was significantly down-expressed in squamous cell carcinoma of the
      cervix compared to the normal cervix (P = 0.003, P < 0.001, and P = 0.001,
      respectively). High ST6Gal I expression was associated with more invasive
      properties of cervical cancer, such as deep stromal invasion, lymph or vascular
      space involvement, and poor differentiation (P = 0.010, P < 0.001, P < 0.001,
      respectively). CONCLUSIONS: A combination of enhanced ST6Gal I mRNA expression
      and decreased mRNA expression from ST3Gal I, ST3Gal III, and ST3Gal IV might be
      important in cervical cancer. Future studies will investigate whether RT-PCR
      detection of the expression of these enzymes can be helpful for prognostic
      purposes.

PMID- 11585424
TI  - Results of reinduction therapy with paclitaxel and carboplatin in recurrent
      epithelial ovarian cancer.
AB  - OBJECTIVE: The purpose of the study was to evaluate the treatment results and
      toxicity of a retreatment regimen of paclitaxel and carboplatin in patients with
      ovarian cancer relapse. METHODS: A retrospective analysis of 241 consecutive
      patients with primary epithelial ovarian cancer receiving paclitaxel and a
      platinum analogue as first-line treatment was performed. Relapse treatment of
      platinum-sensitive patients consisted of paclitaxel (175 mg/m(2)) over 3 h
      followed by carboplatin at an area under the concentration-time curve of 5,
      repeated every 3 weeks. RESULTS: Forty-three patients with relapse were treated
      with paclitaxel and carboplatin after a median progression-free interval from the
      end of first-line chemotherapy of 15.8 months (range 6.0-41.7 months). In
      patients with evaluable disease the overall response rate was 84% (95% CI: 68.0
      93.8%). The progression-free survival and overall survival from start of relapse
      treatment were a median of 9.7 months (range 1.4-26.9 months) and 13.1 months
      (range 4.5-35.5 months), respectively. In a multivariate Cox analysis independent
      prognostic factors for progression-free survival after first relapse were
      response to relapse treatment (P = 0.002, hazard ratio = 13.9) and time to first
      recurrence (P = 0.016, hazard ratio = 0.167). The planned treatment was
      accomplished by 67% of patients. Grade 4 neutrocytopenia over 1 week was observed
      in 9.3% of patients. Grade 1-2 peripheral neuropathy was reported in 30% of
      patients. Only 1 patient had her paclitaxel dose attenuated because of grade 4
      neuropathy. CONCLUSION: Retreatment with paclitaxel and carboplatin in patients
      with platinum-sensitive epithelial ovarian cancer relapse yielded a high response
      rate and encouraging progression-free survival and overall survival. Paclitaxel
      carboplatin reinduction therapy is generally well tolerated and the toxicity is
      manageable.

PMID- 11585425
TI  - Metastatic uterine papillary serous carcinoma to the pericardium.
AB  - BACKGROUND: Uterine papillary serous carcinoma is an aggressive tumor with a high
      propensity for distant spread. Metastases to the heart or pericardium are rare in
      gynecologic malignancies and usually fatal. CASE: A 64-year-old African American
      woman was diagnosed with recurrent uterine papillary serous carcinoma metastatic
      to the pericardium. Her case at presentation was significant for an elevated
      serum CA-125, evidence of metastatic disease to the liver, and massive
      cardiomegaly. Cytologic analysis of fluid obtained by pericardiocentesis
      confirmed recurrence. Despite treatment with paclitaxel and a pleuropericardial
      window, the patient succumbed to her disease. CONCLUSION: The prognosis for
      patients whose recurrent uterine papillary serous carcinoma has metastasized to
      the heart or pericardium is extremely poor. Effective adjuvant and salvage
      therapies are essential.

PMID- 11585426
TI  - Cervical primitive neuroectodermal tumor.
AB  - BACKGROUND: Primitive neuroectodermal tumors (PNETs) are rare and potentially
      aggressive malignancies. CASE: A 24-year-old woman in her eighth week of
      pregnancy presented with a cervical mass. Tissue biopsy demonstrated poorly
      differentiated carcinosarcoma with neuroendocrine features. Immunohistochemical
      studies confirmed the diagnosis of PNET. Treatment included alternating courses
      of cyclophosphamide, adriamycin, vincristine (CAV) and ifosfamide, etoposide
      (IE). A radical hysterectomy with bilateral ovarian transposition and periaortic
      lymphadenectomy was performed with postoperative chemotherapy and radiotherapy.
      The patient remains disease free 2 years from therapy. CONCLUSION: This is a rare
      case of cervical PNET occurring in a pregnant patient. A review of the literature
      indicates that cervical PNET is distinguishable from uterine PNET. This tumor
      affects younger women and may have a different histogenesis. Pregnancy should not
      delay diagnosis of this potentially aggressive tumor.

PMID- 11585427
TI  - Malignant pericardial effusion and cardiac tamponade in endometrial
      adenocarcinoma.
AB  - BACKGROUND: Malignant pericardial effusion as a complication of gynecological
      cancers is a rare occurrence. A review of the literature revealed only two cases
      of pericardial effusion secondary to endometrial adenocarcinoma. We describe
      another patient with FIGO stage IIIA endometrial cancer who developed malignant
      pericardial effusion with cardiac tamponade. CASE: A 57-year-old woman with a
      history of endometrial carcinoma presented with pericardial effusion and cardiac
      tamponade. The patient had undergone total abdominal hysterectomy and bilateral
      salpingo-oophorectomy, followed by three cycles of radiotherapy postoperatively.
      Chest X ray and echocardiogram confirmed the presence of pericardial effusion
      with impending cardiac tamponade. Pericardial biopsy revealed adenocarcinoma. The
      treatment consisted of emergency pericardial window and subsequent therapy with
      tamoxifen. A follow-up after 6 months revealed the patient to be asymptomatic.
      CONCLUSION: Patients with cancer may develop a pericardial effusion for different
      reasons. Early diagnosis of the specific cause is not only useful but also
      essential in determination of the mode of therapy and estimation of prognosis.

PMID- 11585428
TI  - Pregnancy outcomes of patients who conceived within 1 year after chemotherapy for
      gestational trophoblastic tumor: a clinical report of 22 patients.
AB  - OBJECTIVE: The aim of this study was to explore the risk of pregnancy of patients
      who conceived within 1 year after successful chemotherapy for gestational
      trophoblastic tumor (GTT). METHODS: From 1966 to 1996, 22 patients who conceived
      within 1 year after chemotherapy were followed up and analyzed retrospectively.
      RESULTS: Among 22 patients, 9 had term deliveries and 1 had a premature birth, 6
      had induced abortion at the patient's request, and 6 had therapeutic abortion
      because of various indications such as repeated hydatidiform mole (1 case),
      intrauterine death (1 case), inevitable abortion (1 case), and threatened
      abortion (3 cases). The fetal loss rate was 27.1% (6/22). The incidence rate of
      gestational trophoblastic disease (GTD) was 9.1% (2/22). The incidence rate of
      GTT was 4.5% (1/22). The average interval between completion of chemotherapy and
      pregnancy was 10.25 months in the group of term pregnancies and 5.86 months in
      that of fetal loss (P < 0.05), indicating that the longer the interval, the
      lesser the risk of GTD. CONCLUSION: The results suggest that contraception for 1
      year is necessary in patients with GTT after successful chemotherapy. However, in
      the case of a patient who conceives within 1 year, it is not necessary to
      terminate pregnancy, but the pregnancy must be carefully watched.

PMID- 11585429
TI  - Primary ependymoma of the ovary, in which long-term oral etoposide (VP-16) was
      effective in prolonging disease-free survival.
AB  - BACKGROUND: Ovarian ependymoma is an extremely unusual teratoma of the ovary with
      only eight cases previously reported in the literature worldwide. CASE: A 26-year
      old woman presented in 1992 with a sensation of abdominal fullness. The
      laparotomy revealed ovarian cancer (stage III), which proved to be an ependymoma
      pathologically. Three courses of the PVP regimen (cisplatin, vinblastine,
      peplomycin) and pelvic irradiation were administered postoperatively. Oral
      administration of etoposide (VP-16) was initiated after the residual tumor began
      to proliferate, and the tumor decreased in size and never regrew during etoposide
      administration for a total of 5 years and 8 months. The recurrent tumor was
      observed soon after the drug was discontinued. CONCLUSION: Oral administration of
      etoposide was effective in prolonging disease-free survival.

PMID- 11585430
TI  - Pseudo-Meigs' syndrome caused by a hydropic degenerating uterine leiomyoma with
      elevated CA 125.
AB  - BACKGROUND: Uterine leiomyomas rarely cause pseudo-Meigs' syndrome with elevated
      serum CA 125 levels. CASE: A 39-year-old patient with a large uterine leiomyoma
      is described. The associated massive ascites, pleural fluid, and increased CA 125
      level all seemed to be related to the uterine tumor. Hydropic degenerating
      leiomyomas are characterized by focal accumulation of edema and collagen
      deposition. Marked degrees of hydropic degeneration may have resulted in cystic
      degeneration, leading to large myometrial cysts. A presumed direct relation
      between the abundance of intratumoral fluid and presence of ascites seemed
      justified. The increased level of CA 125 most probably resulted from the
      peritoneal mechanical irritation from the large leiomyoma or from a large volume
      of ascites. Having accumulated a sufficient volume and pressure, the ascites
      finds it way through the diaphragm through intercellular gaps and diaphragmatic
      apertures, as well as through small bilateral areas where muscular tissue of the
      diaphragm is replaced by areolar tissue, resulting in the presence of pleural
      fluid. CONCLUSION: The pathophysiology of a uterine leiomyoma mimicking a pelvic
      malignancy is described.

PMID- 11585431
TI  - Serum leptin in patients with vulvar cancer.

PMID- 11585432
TI  - Possible influence of granulocyte colony-stimulating factor and recombinant human
      erythropoietin on human chorionic gonadotropin secretion during chemotherapy for
      choriocarcinoma.

PMID- 11585433
TI  - Re: Mol et al. Distinguishing the benign and malignant adnexal mass: an external
      validation of prognostic models. Gynecol Oncol 2001;80:162-7.

PMID- 11585436
TI  - Serum cytokine concentrations in patients with cervical cancer: interleukin-4,
      interferon-gamma, and monocyte chemoattractant protein-1.

PMID- 11585435
TI  - Preventive gynecologic surgery for BRCA1/2 carriers--information for decision
      making.

PMID- 11585437
TI  - Discovery of 4-[(Z)-(4-bromophenyl)- (ethoxyimino)methyl]-1'-[(2,4-dimethyl-3-
      pyridinyl)carbonyl]-4'-methyl-1,4'- bipiperidine N-oxide (SCH 351125): an orally
      bioavailable human CCR5 antagonist for the treatment of HIV infection.
AB  - Structure-activity studies on piperidino-piperidine 3 led to the discovery of SCH
      351125 (1), a selective CCR5 antagonist with potent activity against RANTES
      binding (K(i) = 2 nM), which possesses subnanomolar activity in blocking viral
      entry and has excellent antiviral potency versus a panel of primary HIV-1 viral
      isolates. Compound 1, which has good oral bioavailability in rats, dogs, and
      monkeys, is proposed as a potential therapeutic agent for the treatment of HIV-1
      and has entered human clinical trials.

PMID- 11585438
TI  - Piperazine-based CCR5 antagonists as HIV-1 inhibitors. II. Discovery of 1-[(2,4
      dimethyl-3-pyridinyl)carbonyl]-4- methyl-4-[3(S)-methyl-4-[1(S)-[4
      (trifluoromethyl)phenyl]ethyl]-1-piperazinyl]- piperidine N1-oxide (Sch-350634),
      an orally bioavailable, potent CCR5 antagonist.
AB  - Truncation of the original piperidino-2(S)-methyl piperazine lead structure 2,
      from a family of muscarinic antagonists, gave compound 8 which has improved
      selectivity for the HIV-1 co-receptor CCR5 over muscarinic receptors. Further
      optimization for pharmacokinetic properties afforded Sch-350634 (1), a
      prototypical piperazine-based CCR5 antagonist, which is a potent inhibitor of HIV
      1 entry and replication in PBMCs. The title compound (1) has excellent oral
      bioavailability in rat, dog, and monkey.

PMID- 11585439
TI  - Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)-
      [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent,
      selective, and orally bioavailable aggrecanase inhibitors.
AB  - A pharmacophore model of the P1' site, specific for aggrecanase, was defined
      using the specificity studies of the matrix metalloproteinases and the similar
      biological activity of aggrecanase and MMP-8. Incorporation of the side chain of
      a tyrosine residue into compound 1 as the P1' group provided modest selectivity
      for aggrecanase over MMP-1, -2, and -9. A cis-(1S)(2R)-amino-2-indanol scaffold
      was incorporated as a tyrosine mimic (P2') to conformationally constrain 2.
      Further optimization resulted in compound 11, a potent, selective, and orally
      bioavailable inhibitor of aggrecanase.

PMID- 11585440
TI  - Discovery of macrocyclic hydroxamic acids containing biphenylmethyl derivatives
      at P1', a series of selective TNF-alpha converting enzyme inhibitors with potent
      cellular activity in the inhibition of TNF-alpha release.
AB  - SAR exploration at P1' using an anti-succinate-based macrocyclic hydroxamic acid
      as a template led to the identification of several bulky biphenylmethyl P1'
      derivatives which confer potent porcine TACE and anti-TNF-alpha cellular
      activities with high selectivity versus most of the MMPs screened. Our studies
      demonstrate for the first time that TACE has a larger S1' pocket in comparison to
      MMPs and that potent and selective TACE inhibitors can be achieved by
      incorporation of sterically bulky P1' residues.

PMID- 11585441
TI  - Potent and selective ET-A antagonists. 1. Syntheses and structure-activity
      relationships of N-(6-(2-(aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide derivatives.
AB  - Modifications to the ET(A/B) mixed type compounds 1 (Ro. 46-2005) and 2
      (bosentan) were performed. Introduction of a pyrimidine group into 1 resulted in
      a dramatic increase in affinity for the ET(A) receptor, and the subsequent
      optimization of substituents on the pyrimidine ring led us to the discovery of N
      (6-(2-((5-bromo-2-pyrimidinyl)oxy)ethoxy)-5-(4-methylphenyl)-4-pyrimidinyl)-4
      tert-butylbenzenesulfonamide (7k), which showed an extremely high affinity for
      the human cloned ET(A) receptor (K(i) = 0.0042 +/- 0.0038 nM) and an ET(A/B)
      receptor selectivity up to 29 000 (K(i) = 130 +/- 50 nM for the human cloned
      ET(B) receptor). The compound was designed on the hypothesis that the hydrogen
      atom of the hydroxyl group in 1 and 2 played a role not as a proton donor but as
      an acceptor in the possible hydrogen bonding with Tyr129. Since the incorporation
      of a pyrimidinyl group into the hydroxyethoxy side chain of the nonselective
      antagonist (1) dramatically enhanced both the ET(A) receptor affinity and
      selectivity, and since similar results were obtained from the benzene analogues,
      we put forward the hypothesis that a "pyrimidine binding pocket" might exist in
      the ET(A) receptor.

PMID- 11585442
TI  - Potent and selective ET-A antagonists. 2. Discovery and evaluation of potent and
      water soluble N-(6-(2-(aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide derivatives.
AB  - In the preceding article,(1) we outlined the discovery and structure-activity
      relationship of a potent and selective ET(A) receptor antagonist 1 and its
      related compounds. Metabolites of 1 having potent selective ET(A) receptor
      antagonist activity were identified. This study suggested the metabolic pathways
      of 1 were considerably affected by species. Consequently, structural modification
      of 1 intended to improve the complexity of the metabolic pathway, and water
      solubility was performed. The subsequent introduction of a hydroxyl group into
      the tert-butyl moiety of 1 led to the discovery of our new clinical candidate,
      6b, which showed a higher water solubility, a uniform metabolic pathway among
      species, and very high affinity and selectivity for the human ET(A) receptor
      (K(i) for ET(A) receptor: 0.015 +/- 0.004 nM; for ET(B) receptor: 41 +/- 21 nM).

PMID- 11585443
TI  - From hit to lead. Combining two complementary methods for focused library design.
      Application to mu opiate ligands.
AB  - Compound 1 obtained by random screening and displaying a micromolar activity on
      the mu opiate receptor was chosen as a starting point for optimization. Two
      complementary concepts of similarity were used for the design of analogues and
      compared. These are based, respectively, on a computer-aided comparison of
      pharmacophoric patterns and on topological similarity. The structure-activity
      relationships are discussed in light of both similarity concepts. Compound 40, an
      N-methyl-3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decyl)acetamide derivative,
      designed by combining the structure-activity relationships enlightened by each
      method, has a subnanomolar affinity for mu (h) receptor (IC(50) = 0.9 nM). It is
      a promising lead, allowing the design of a new series of analogues substituted at
      the N-3 of the spirocycle moiety.

PMID- 11585444
TI  - From hit to lead. Analyzing structure-profile relationships.
AB  - Two compounds, obtained by random screening, and displaying micromolar activities
      on the mu opiate receptor were used as starting points for optimization. In that
      work, the traditional concept of the activity of a compound (related to one or a
      few targets) was extended to the comprehensive pharmacological profile of that
      compound on more than 70 receptors, transporters, and channels relevant to a CNS
      oriented project. Using the two complementary design strategies based on two
      similarity concepts described in the previous paper, we have obtained analogues
      with IC(50) values ranging between 0.9 nM and a few micromolar on the mu receptor
      and displaying qualitatively different profiles. We discuss here, both on a case
      by-case basis and from a statistical standpoint, the pharmacological profiles in
      light of the two similarity concepts.

PMID- 11585445
TI  - Synthesis of potent C(2)-symmetric, diol-based hiv-1 protease inhibitors.
      Investigation of thioalkyl and thioaryl P1/P1' substituents.
AB  - The synthesis of novel, potent diol-based HIV-1 protease inhibitors, having
      either -SAr, -SCH(2)Ar, or -SCH(2)R groups as P1/P1' substituents is described.
      They can be prepared using a straightforward synthesis involving a thiol
      nucleophilic ring opening of a diepoxide. Inhibitor 13 was found to be a potent
      inhibitor of HIV-1 PR, showing good antiviral activity in a cell-based assay.

PMID- 11585446
TI  - Synthesis of novel, potent, diol-based HIV-1 protease inhibitors via
      intermolecular pinacol homocoupling of (2S)-2-benzyloxymethyl-4-phenylbutanal.
AB  - The synthesis of novel, potent, diol-based HIV-1 protease inhibitors, having
      phenethyl groups (-CH(2)CH(2)Ph) in P1/P1' position is described. An
      intermolecular pinacol homocoupling of (2S)-2-benzyloxymethyl-4-phenylbutanal 16
      was the key step in the synthesis. From this reaction sequence four carba
      analogues, compounds 8a, 8b, 9a, and 9b, were prepared, having the inverted
      configuration of one or both of the stereogenic centers carrying the diol
      hydroxyls as compared to the parent series represented by inhibitors 6 and 7.
      Inhibitor 8b was found to be a potent inhibitor of HIV-1 protease (PR), showing
      excellent antiviral activity in the cell-based assay and in the presence of 40%
      human serum. The absolute stereochemistry of the central diol of the potent
      inhibitor (8b) was determined from the X-ray crystallographic structure of its
      complex with HIV-1 PR.

PMID- 11585447
TI  - Are free energy calculations useful in practice? A comparison with rapid scoring
      functions for the p38 MAP kinase protein system.
AB  - Precise thermodynamic integration free energy simulations have been applied to a
      congeneric series of 16 inhibitors to the p38 MAP kinase protein for which the
      experimental binding data (IC(50)) is known. The relative free energy of binding
      for each compound has been determined. For comparison, the same series of
      compounds have also scored using the best rapid scoring functions used in
      database screening. From the results of these calculations, we find (1) that
      precise free energy simulations allow predictions that are reliable and in good
      agreement with experiment; (2) that predictions of lower reliability, but still
      in good qualitative agreement with experiment, can be obtained using the OWFEG
      free energy grid method, at a much lower computational cost; (3) and that other
      methods, not based on free energy simulations yield results in much poorer
      agreement with experiment. A new predictive index, which measures the reliability
      of a prediction method in the context of normal use, is defined and calculated
      for each scoring method. Predictive indices of 0.84, 0.56, 0.04, -0.05, and 0.25
      are calculated for thermodynamic integration, OWFEG, ChemScore, PLPScore, and
      Dock Energy Score, respectively, where +1.0 is perfect correct prediction, -1.0
      is perfect incorrect prediction, and 0.0 is random.

PMID- 11585448
TI  - Statistical molecular design, parallel synthesis, and biological evaluation of a
      library of thrombin inhibitors.
AB  - A library of thrombin inhibitors has been designed using statistical molecular
      design. An aromatic scaffold was used, with three varied positions corresponding
      to three pockets at the active site of thrombin (the S-, P-, and D-pockets). The
      selection was performed in the building block space, and previously acquired data
      were included in the design procedure. The design resulted in six, four, and six
      building blocks for the first (S), second (P), and third (D) pockets,
      respectively. A second round of selection applied to the combined selected
      building blocks resulted in a subset of 18 compounds. The selected library was
      synthesized in parallel and biologically evaluated. The compounds were analyzed
      with respect to their inhibition (pIC(50)) of thrombin; membrane permeability,
      estimated by migration behavior in micellar media (CE log k') and pK(a); and
      specificity with respect to inhibition (K(i)) of trypsin. Multivariate QSAR
      studies of the responses yielded valuable results and information that could only
      be found using statistical molecular design in combination with multivariate
      analysis.

PMID- 11585449
TI  - Synthesis and biological evaluation of s-triazine substituted polyamines as
      potential new anti-trypanosomal drugs.
AB  - The P2 transporter is a nucleoside transporter which is unique to the protozoan
      parasite Trypanosoma brucei, the causative organism of Human African
      Trypanosomasis. The transporter has been shown to bind some structural motifs not
      recognized by other transporters. In this paper we describe the use of the
      melamine motif, a substrate of the P2 transporter, as a potential tool to
      selectively deliver polyamine analogues to the parasites. The synthesis of a
      number of polyamine analogues attached to a variety of melamine analogues is
      described. Many of the compounds were shown to competitively inhibit uptake of
      adenosine, indicating that they are recognized by the transporter. Some of the
      compounds showed good in vitro activity against the parasites.

PMID- 11585450
TI  - Synthesis, DNA cross-linking activity, and cytotoxicity of dimeric mitomycins.
AB  - Dimeric DNA cross-linking compounds have emerged as important new antitumor
      agents. We report the synthesis and biochemical evaluation of a select set of
      dimeric mitomycins in which the two mitomycin units are tethered at either the
      mitomycin C(7) amino or the aziridine N(1a) positions. Significantly, mitomycin C
      (1) itself is the prototypical bioreductive DNA cross-linking agent. DNA cross
      linking experiments using a denaturing-gel-electrophoresis-based assay showed
      that the extent of DNA cross-linking for select dimeric mitomycins can exceed
      that of the parent compound, mitomycin C, and that the reaction proceeds, in
      part, at the two distal C(1) sites in the mitomycins. The efficiency of DNA cross
      linking depended on the nature of the linker and the position of linker unit's
      attachment. When we compared the efficiency of DNA cross-linking for the dimeric
      mitomycins with their in vitro cytotoxicities in cultured human tumor cells, we
      observed a poor correlation. The mitomycins that gave the highest levels of DNA
      cross-linked adducts displayed the weakest cytotoxicities. These findings
      determined that the denaturing-gel-electrophoresis-based assay was a poor
      predictor of cytotoxic activity.

PMID- 11585451
TI  - A new class of ibuprofen derivatives with reduced gastrotoxicity.
AB  - A new series of nonsteroidal antiinflammatory drugs (NSAIDs) obtained by linking
      ibuprofen to selected furoxan moieties and to related furazans were synthesized
      and tested for their antiinflammatory, antiaggregatory, and ulcerogenic
      properties. All the derivatives are endowed with antiinflammatory activity
      comparable to that of ibuprofen, but, unlike this drug, they display reduced
      acute gastrotoxicity. The masking of the ibuprofen-free carboxylic group seems to
      be principally at the basis of this reduced topical irritant action. The two
      furoxan derivatives 8 and 9 also trigger potent antiaggregatory effects,
      principally as a consequence of their NO-donor ability.

PMID- 11585453
TI  - 1,2-Benzothiazine 1,1-dioxide P(2)-P(3) peptide mimetic aldehyde calpain I
      inhibitors.
AB  - A series of peptide mimetic aldehyde inhibitors of calpain I was prepared in
      which the P(2) and P(3) amino acids were replaced by substituted 3,4-dihydro-1,2
      benzothiazine-3-carboxylate 1,1-dioxides. The effect of 2, 6, and 7-benzothiazine
      substituents and the P(1) amino acid was examined. Potency of these inhibitors,
      15c-p, against human recombinant calpain I is particularly dependent upon the 2
      substituent, with methyl and ethyl generally more potent than hydrogen,
      isopropyl, isobutyl, or benzyl. The more potent diastereomer of 15m possesses the
      (S) absolute configuration at the 3-position of the 3,4-dihydro-1,2
      benzothiazine. Potency of the best inhibitors in this series (IC(50) = 5-7 nM)
      compares favorably with that of conventional N-benzyloxycarbonyl dipeptide
      aldehyde inhibitors bearing L-Leu or L-Val residues at P(2). The achiral
      unsaturated 1,2-benzothiazine analogues 26a-d are also potent calpain I
      inhibitors, while 3,4-dihydro-2,1-benzoxathiin (15a,b), 1,2,4-benzothiadiazine
      (32a,b), and tetrahydroisoquinolinone (36a,b) analogues are less potent.

PMID- 11585452
TI  - Selective inhibition of ICAM-1 and E-selectin expression in human endothelial
      cells. 2. Aryl modifications of 4-(aryloxy)thieno[2,3-c]pyridines with fine
      tuning at C-2 carbamides.
AB  - The elevated expression of cell adhesion molecules (CAMs) on the lumenal surface
      of vascular endothelial cells is a critical early event in the complex
      inflammatory process. The adhesive interactions of these CAMs that include E
      selectin, ICAM-1, and VCAM-1 with their counter-receptors on leukocytes, such as
      integrins of the alpha(L)beta(2) family, result in migration of the leukocytes to
      the site of inflammation and cause tissue injury. Pharmaceutical agents that
      could suppress the induced expression of one or more of these cell adhesion
      molecules would provide a novel mechanism to attenuate the inflammatory responses
      associated with chronic inflammatory diseases. A-205804 (1), a potent and
      selective inhibitor of the induced expression of E-selectin and ICAM-1 over VCAM
      1, was further modified with emphasis at the C-4 and C-2 positions to identify a
      more potent drug candidate with a good pharmacokinetic profile and physical
      properties. Replacement of the C-4 sulfur linkage in 1 with an oxygen atom
      eliminated one of the two major metabolites for this lead molecule. The para
      position of the 4-phenoxy group of the thieno[2,3-c]pyridine lead is found to be
      very critical for a higher in vitro potency and selectivity of E-selectin and
      ICAM-1 over VCAM-1 expression. This position is presumably close to the solvent
      accessible region of the target protein-inhibitor complex. An attempt to install
      a water-solubilizing group at the para-position of the phenoxy group to increase
      the aqueous solubility of this lead series through various linkages failed to
      provide an ideal inhibitor. Only small substituents such as fluorine are
      tolerated at the meta- and ortho-positions of the 4-phenoxy to retain a good in
      vitro potency. Bromo, trifluoromethyl, pyrazol-1-yl, and imidazol-1-yl are among
      the better substituents at the para-position. With fine-tuning at the C-2
      position we discovered a series of very potent (IC(50) < 5 nM for ICAM-1) and
      selective (>200-fold vs VCAM-1) inhibitors with a good pharmacokinetic profile.
      Demonstrated efficacy in a rat rheumatoid arthritis model and in a mice asthma
      model with selected compounds is also reported.

PMID- 11585454
TI  - Palmitoyl derivatives of GpMBP epitopes: T-cell response and peptidases
      susceptibility.
AB  - We report for the first time the immunoadjuvant effects of lipoconjugation of
      peptide antigens in an in vitro system by using CD4+ T-cells. The lipopeptides
      obtained by conjugating a palmitoyl moiety at the N(alpha)-terminal of Gln(74) or
      at the epsilon-NH(2) of Lys(75) of GpMBP(74-85) induced increased T-cell
      responsiveness compared to the native nonlipidated peptide. On the other hand,
      lipoderivatives of GpMBP(82-98) did not increase the T-cell response,
      demonstrating that the superagonist inducing effect of lipoconjugation is epitope
      specific. Digestion of the two native peptides with cathepsin D and L, both
      implicated in antigen processing, and with a complete lysosomal fraction of a EBV
      transformed B cell line shows that GpMBP(74-85) is resistant to cellular
      proteases, while GpMBP(82-98) is easily digested by these enzymes. These results
      suggest that the first prerequisite for increasing the T-cell response by
      lipoconjugation is the stability of the native peptide to peptidases, providing
      an important insight into the understanding of the immunoadjuvant effect of
      lipoderivative antigens.

PMID- 11585455
TI  - Hypoxia-selective antitumor agents. 16. Nitroarylmethyl quaternary salts as
      bioreductive prodrugs of the alkylating agent mechlorethamine.
AB  - Nitrobenzyl quaternary salts of nitrogen mustards have been previously reported
      as hypoxia-selective cytotoxins. In this paper we describe the synthesis and
      evaluation of a series of heterocyclic analogues, including pyrrole, imidazole,
      thiophene, and pyrazole examples, chosen to cover a range of one-electron
      reduction potentials (from -277 to -511 mV) and substitution patterns. All
      quaternary salt compounds were less toxic in vitro than mechlorethamine, and all
      were more toxic under hypoxic than aerobic conditions, although the differentials
      were highly variable within the series. The most promising analogue, imidazole 2,
      demonstrated DNA cross-linking selectively in hypoxic RIF-1 cells, and was active
      in vivo in combination with radiation or cisplatin. However, 2 also produced
      unpredictable toxicity in vivo, suggestive of nonspecific nitrogen mustard
      release, and this has restricted further development of these compounds as
      hypoxia-selective cytotoxins.

PMID- 11585456
TI  - Long lasting antinociceptive properties of enkephalin degrading enzyme (NEP and
      APN) inhibitor prodrugs.
AB  - Prodrugs of phosphinic dual inhibitors of the enkephalin degrading enzymes,
      neutral endopeptidase (NEP) and aminopeptidase N (APN), corresponding to the
      formula H(3)N(+)CH(R(1))P(O)(OR)CH(2)CH(CH(2)Bip)CONHCH(CH(3))COOCH(2)Ph, with
      R(1) = CH(3) or Ph and R being a benzyl ester, a S-acyl-2-thioethyl derivative,
      or an acyloxyalkyl group, were synthesized to improve the poor central
      bioavailability of their precursors. As expected, these compounds (50 mg/kg, iv
      or ip) induced long lasting ( approximately 2 h) antinociceptive responses in the
      hot plate test in mice with a ceiling effect varying between 25 and 42% of
      analgesia. A very rapid hydrolysis of the carboxylate ester contrasting with a
      slow deprotection of the phosphinate group (t(1/2) approximately 1 h) was
      observed in serum while 80% of free drug was obtained after 1 h incubation with
      brain membranes. These results account for the long duration of action observed
      with these prodrugs.

PMID- 11585459
TI  - Health care practitioners and organizations prepare for approaching HIPAA
      deadlines.

PMID- 11585457
TI  - Synthesis and antiviral activity of novel 5-(1-cyanamido-2-haloethyl) and 5-(1
      hydroxy(or methoxy)-2-azidoethyl) analogues of uracil nucleosides.
AB  - A new class of 5-(1-cyanamido-2-haloethyl)-2'-deoxyuridines (4-6) and
      arabinouridines (7, 8) were synthesized by the regiospecific addition of
      halogenocyanamides (X-NHCN) to the 5-vinyl substituent of the respective 5-vinyl
      2'-deoxyuridine (2) and 2'-arabinouridine (3). Reaction of 2 with sodium azide,
      ceric ammonium nitrate, and acetonitrile-methanol or water afforded the 5-(1
      hydroxy-2-azidoethyl)-(10) and 5-(1-methoxy-2-azidoethyl)-2'-deoxyuridines (11).
      In vitro antiviral activities against HSV-1-TK(+) (KOS and E-377), HSV-1-TK(-),
      HSV-2, VZV, HCMV, and DHBV were determined. Of the newly synthesized compounds, 5
      (1-cyanamido-2-iodoethyl)-2'-deoxyuridine (6) exhibited the most potent anti-HSV
      1 activity, which was equipotent to acyclovir and superior to 5-ethyl-2'
      deoxyuridine (EDU). In addition, it was significantly inhibitory for thymidine
      kinase deficient strain of HSV-1 (EC(50) = 2.3-15.3 microM). The 5-(1-cyanamido-2
      haloethyl)-2'-deoxyuridines (4-6) all were approximately equipotent against HSV-2
      and were approximately 1.5- and 15-fold less inhibitory for HSV-2 than EDU and
      acyclovir, respectively. Compounds 4-6 were all inactive against HCMV but
      exhibited appreciable antiviral activity against VZV. Their anti-VZV activity was
      similar or higher to that of EDU and approximately 5-12-fold lower than that of
      acyclovir. The 5-(1-cyanamido-2-haloethyl)-(7,8) analogues of arabinouridine were
      moderately inhibitory for VZV and HSV-1 (strain KOS), whereas compounds 10 and 11
      were inactive against herpes viruses. Compounds 5 and 6 also demonstrated modest
      anti-hepatitis B virus activity against DHBV (EC(50) = 19.9-23.6 microM).
      Interestingly, the related 5-(1-azido-2-bromoethyl)-2'-deoxyuridine (1n) analogue
      proved to be markedly inhibitory to DHBV replication (EC(50) = 2.6-6.6 microM).
      All compounds investigated exhibited low host cell toxicity to several stationary
      and proliferating host cell lines as well as mitogen-stimulated proliferating
      human T lymphocytes.

PMID- 11585460
TI  - Brain exhibit starts 6-year US journey.

PMID- 11585461
TI  - Ophthalmologists eye new examination tool.

PMID- 11585462
TI  - HMOs report quality improvements.

PMID- 11585463
TI  - From the Food and Drug Administration.

PMID- 11585466
TI  - High-density lipoprotein cholesterol and risk of stroke.

PMID- 11585468
TI  - Relationship of physician volume to mortality after acute myocardial infarction.

PMID- 11585470
TI  - Reimbursement as incentive to improve physicians' quality of care.

PMID- 11585472
TI  - Liposuction in medical offices.

PMID- 11585474
TI  - Managed care: success or failure.

PMID- 11585475
TI  - Managed care: success or failure.

PMID- 11585476
TI  - Managed care: success or failure.

PMID- 11585477
TI  - Ethical issues in the reporting of clinical trials.

PMID- 11585479
TI  - Pain associated with injection using frozen vs room-temperature needles.

PMID- 11585480
TI  - Single vs weekly courses of antenatal corticosteroids for women at risk of
      preterm delivery: A randomized controlled trial.
AB  - CONTEXT: The practice of administering weekly courses of antenatal
      corticosteroids to pregnant women at risk of preterm delivery is widespread, but
      no randomized trial has established the efficacy or safety of this practice.
      OBJECTIVES: To evaluate the efficacy of weekly administration of antenatal
      corticosteroids compared with a single course in reducing the incidence of
      neonatal morbidity and to evaluate potential complications of weekly treatment.
      DESIGN AND SETTING: Randomized, double-blind, placebo-controlled intention-to
      treat trial conducted in 13 academic centers in the United States from February
      1996 through April 2000. PARTICIPANTS: A total of 502 pregnant women between 24
      and 32 completed weeks' gestation who were at high risk of preterm delivery.
      INTERVENTION: All patients received a complete single course of antenatal
      corticosteroids (either betamethasone, 12 mg intramuscularly repeated once in 24
      hours for 2 doses, or dexamethasone, 6 mg intramuscularly repeated every 12 hours
      for 4 doses). Participants who had not delivered 1 week after receipt of the
      single course were randomly assigned to receive either betamethasone, 12 mg
      intramuscularly repeated once in 24 hours for 2 doses every week until 34 weeks'
      gestation or delivery, whichever came first (n = 256), or a similarly
      administered placebo (n = 246). MAIN OUTCOME MEASURE: Composite neonatal
      morbidity (including severe respiratory distress syndrome, bronchopulmonary
      dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia,
      proven sepsis, necrotizing enterocolitis, or perinatal death). RESULTS: Composite
      morbidity occurred in 22.5% of the weekly-course group vs 28.0% of the single
      course group (unadjusted relative risk, 0.80; 95% confidence interval, 0.59
      1.10). Neither group assignment nor the number of treatment courses was
      associated with a reduction in composite morbidity. CONCLUSIONS: Weekly courses
      of antenatal corticosteroids did not reduce composite neonatal morbidity compared
      with a single course of treatment. Weekly courses of antenatal corticosteroids
      should not be routinely prescribed for women at risk of preterm delivery.

PMID- 11585481
TI  - Initial effects of graduated driver licensing on 16-year-old driver crashes in
      North Carolina.
AB  - CONTEXT: Since 1997, 32 states have enacted graduated driver licensing (GDL)
      systems to reduce crash rates among young novice drivers. OBJECTIVE: To determine
      the initial effect of the North Carolina GDL system on crashes among 16-year-old
      drivers. DESIGN, SETTING, AND SUBJECTS: Comparison of population-based North
      Carolina motor vehicle crash rates before (1996-1997) and after (1999) 16-year
      old drivers were licensed under the GDL system. To control for other factors that
      might have influenced crashes, changes for 16-year-old drivers were compared with
      those of drivers 25 to 54 years of age. Crashes per licensed driver were also
      examined. INTERVENTION: The North Carolina GDL system, enacted December 1, 1997,
      requires beginning drivers 15 to 17 years of age to hold level 1 licenses,
      allowing driving only while supervised by a designated adult for a full year;
      followed by level 2 licensure, allowing unsupervised driving from 5 AM to 9 PM
      and supervised driving at any time for at least 6 months; and, finally, level 3-a
      full, unrestricted license. MAIN OUTCOME MEASURES: Rates of motor vehicle crashes
      among 16-year-old drivers in 1996-1997 vs 1999, overall and by crash severity
      (fatal, injury, and noninjury), time (night vs day), type (single vs multiple
      vehicle), driver alcohol use, and driving environment (more vs less rural
      counties). RESULTS: Crash rates declined sharply for all levels of severity among
      16-year-old drivers after the GDL program was implemented. Following GDL, 16-year
      old driver crashes were substantially less likely. Comparing 1996 with 1999,
      fatal crashes declined 57%, from 5 to 2 per 10 000 population (rate ratio [RR],
      0.43; 95% confidence interval [CI], 0.27-0.70); crashes with no or minor injuries
      decreased 23%, from 1068 to 826 per 10 000 (RR, 0.77; 95% CI, 0.75-0.80).
      Nighttime crashes were 43% less likely (156 vs 88 per 10 000; RR, 0.57; 95% CI,
      0.52-0.61) and daytime crashes decreased by 20% (951 vs 764 per 10 000; RR, 0.80;
      95% CI, 0.78-0.83). Single-vehicle crashes (245 vs 175; RR, 0.71; 95% CI, 0.67
      0.76) declined somewhat more than multiple-vehicle crashes (866 vs 681; RR, 0.79;
      95% CI, 0.76-0.81). CONCLUSION: In its initial years, the North Carolina GDL
      system produced substantial declines in 16-year-old driver crashes.

PMID- 11585482
TI  - Graduated driver licensing in Michigan: early impact on motor vehicle crashes
      among 16-year-old drivers.
AB  - CONTEXT: Graduated driver licensing (GDL) programs are being adopted in many
      states to address the high rate of motor vehicle fatalities among teens by
      requiring teenaged drivers to gain experience and maturity under conditions of
      relatively low crash risk before gaining full driving privileges. OBJECTIVE: To
      evaluate the early impact of Michigan's GDL program on traffic crashes among 16
      year-old drivers. DESIGN, SETTING, AND SUBJECTS: Analysis of Michigan motor
      vehicle crash data from 1996 (before GDL program implementation) vs 1998 and 1999
      (after GDL program implementation) for 16-year-olds, adjusting for trends among
      persons 25 years or older. INTERVENTION: Michigan's GDL program, instituted April
      1, 1997, for teens younger than 18 years entering the driver license system,
      includes 3 licensure levels, each with driving restrictions and requirements to
      progress to the next level. Requirements include extended, supervised practice in
      the learning level, 2-phase driver education, and night driving restrictions in
      the intermediate level. MAIN OUTCOME MEASURES: Rates in 1996 vs 1998 and 1999 for
      all police-reported crashes; for fatal injury, nonfatal injury, and
      fatal/nonfatal injury combined crashes; for day, evening, and night crashes; for
      single-vehicle and multivehicle crashes; and for alcohol-related crashes.
      RESULTS: Overall, the rate of 16-year-old drivers (per 1000 population) involved
      in crashes declined from 154 in 1996 to 111 in 1999 (relative risk [RR], 0.72;
      95% confidence interval [CI], 0.71-0.73). After adjusting for populationwide
      trends, the overall crash risk for 16-year-olds was significantly reduced in 1999
      from 1996 by 25% (adjusted RR, 0.75; 95% CI, 0.74-0.77). There were also
      significant reductions for nonfatal injury and combined fatal and nonfatal
      crashes; for day, evening, and night crashes; and for single-vehicle and
      multivehicle crashes. Fatal crashes declined from 1996 to 1999, but not
      significantly (RR, 0.74; 95% CI, 0.49-1.14), and alcohol-related crashes
      continued at a low rate (RR, 1.01; 95% CI, 0.80-1.29). CONCLUSIONS: Analysis of
      the first 2 full calendar years following Michigan's GDL program implementation
      indicates substantial crash reductions among 16-year-olds. Future research is
      necessary to determine if these reductions are maintained and if other
      jurisdictions achieve similar results.

PMID- 11585483
TI  - Leg symptoms in peripheral arterial disease: associated clinical characteristics
      and functional impairment.
AB  - CONTEXT: Persons with lower-extremity peripheral arterial disease (PAD) are often
      asymptomatic or have leg symptoms other than intermittent claudication (IC).
      OBJECTIVE: To identify clinical characteristics and functional limitations
      associated with a broad range of leg symptoms identified among patients with PAD.
      DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 460 men and women
      with PAD and 130 without PAD, who were identified consecutively, conducted
      between October 1998 and January 2000 at 3 Chicago-area medical centers. MAIN
      OUTCOME MEASURES: Ankle-brachial index score of less than 0.90; scores from 6
      minute walk, accelerometer-measured physical activity over 7 days, repeated chair
      raises, standing balance (full tandem stand), 4-m walking velocity, San Diego
      claudication questionnaire, Geriatric Depression Score Short-Form, and the
      Walking Impairment Questionnaire. RESULTS: All groups with PAD had poorer
      functioning than participants without PAD. The following values are for patients
      without IC vs those with IC. Participants in the group with leg pain on exertion
      and rest (n = 88) had a higher (poorer) score for neuropathy (5.6 vs 3.5;
      P<.001), prevalence of diabetes mellitus (48.9% vs 26.7%; P<.001), and spinal
      stenosis (20.8% vs 7.2%; P =.002). The atypical exertional leg pain/carry on
      group (exertional leg pain other than IC associated with walking through leg pain
      [n = 41]) and the atypical exertional leg pain/stop group (exertional leg pain
      other than IC that causes one to stop walking [n = 90]) had better functioning
      than the IC group. The group without exertional leg pain/inactive (no exertional
      leg pain in individual who walks </=6 blocks per week [n = 28]) and the leg pain
      on exertion and rest group had poorer functioning than those with IC. Adjusting
      for age, sex, race, and comorbidities and compared with IC, participants with
      atypical exertional leg pain/carry on achieved a greater distance on the 6-minute
      walk (404.3 vs 328.5 m; P<.001) and were less likely to stop during the 6-minute
      walk (6.8% vs 36%; P =.002). The group with pain on exertion and rest had a
      slower time for completing 5 chair raises (13.5 vs 11.9 seconds; P =.009),
      completed the tandem stand less frequently (37.5% vs 60.0%; P =.004), and had a
      slower 4-m walking velocity (0.80 vs 0.90 m/s; P<.001). CONCLUSIONS: There is a
      wide range of leg symptoms in persons with PAD beyond that of classic IC.
      Comorbid disease may contribute to these symptoms in PAD. Functional impairments
      are found in every PAD symptom group, and the degree of functional limitation
      varies depending on the type of leg symptom.

PMID- 11585484
TI  - Coprescribing and codispensing of cisapride and contraindicated drugs.
AB  - CONTEXT: Cisapride, an oral prokinetic drug indicated for the symptomatic
      treatment of nocturnal heartburn due to gastroesophageal reflux disease, was
      approved by the US Food and Drug Administration in July 1993. After reports of
      serious cardiac arrhythmias and deaths during administration of cisapride, most
      involving concomitant exposure to another drug, a series of label changes and
      warnings were issued in February 1995, October 1995, June 1998, and June 1999.
      Cisapride was removed from general distribution in July 2000. OBJECTIVE: To
      determine the frequency of contraindicted coprescribing and codispensings, in
      which cisapride and a contraindicated drug were prescribed or dispensed to the
      same patient for overlapping periods, and the proportion of contraindicated
      coprescribing by the same physicians and codispensing by the same pharmacies.
      DESIGN AND SETTING: Retrospective study of prescription claims from a managed
      care organization database for all patients with cisapride prescriptions between
      July 1993 and December 1998. PARTICIPANTS: A total of 38 757 adult and pediatric
      patients who had a cisapride prescription immediately preceded by at least 60
      days of insurance eligibility. MAIN OUTCOME MEASURE: Proportion of cisapride
      prescriptions or dispensing occurring during the same treatment period as a drug
      contraindicated at that time prescribed by the same physicians or dispensed by
      the same pharmacies. RESULTS: Of 131 485 cisapride prescriptions dispensed after
      the warnings began, 4414 (3.4%) overlapped with at least 1 drug contraindicated
      in the labeling at the time of the prescription. Of all overlapping prescription
      pairs, 2190 (50%) were by the same physicians, 3908 (89%) were by the same
      pharmacies, and 765 (17%) were dispensed on the same day. CONCLUSION:
      Prescriptions dispensed by the same pharmacies accounted for a far higher
      proportion of contraindicated medication pairs than prescriptions from the same
      physicians. The pharmacy may be an important and underutilized intervention point
      to prevent contraindicated drugs from being used together.

PMID- 11585485
TI  - The rational clinical examination. Does this patient have a torn meniscus or
      ligament of the knee? Value of the physical examination.
AB  - CONTEXT: While most meniscal or ligamentous knee injuries heal with nonoperative
      treatments, a subset should be treated with arthroscopic or open surgery.
      OBJECTIVE: To analyze the accuracy of the clinical examination for meniscal or
      ligamentous knee injuries. DATA SOURCES: MEDLINE (1966-December 31, 2000) and
      HealthSTAR (1975-December 31, 2000) databases were searched for English-language
      articles describing the diagnostic accuracy of individual examination items for
      the knee and a combination of physical examination items (composite examination).
      Other data sources included reference lists from relevant articles. STUDY
      SELECTION: Studies selected for data extraction were those that compared the
      performance of the physical examination of the knee with a reference standard,
      such as arthroscopy, arthrotomy, or magnetic resonance imaging. Eighty-eight
      articles were identified, of which 23 (26%) met inclusion criteria. DATA
      EXTRACTION: A rheumatologist and an orthopedic surgeon independently reviewed
      each article using a standardized rating scale that scored the assembly of the
      study, the relevance of the patients enrolled, the appropriateness of the
      reference standard, and the blinding of the examiner. DATA SYNTHESIS: Summary
      likelihood ratios (LRs) were estimated from random effects models. The summary
      LRs for physical examination for tears of the anterior cruciate ligament, using
      the anterior drawer test, were 3.8 (95% confidence interval [CI], 0.7-22.0) for a
      positive examination and 0.30 (95% CI, 0.05-1.50) for a negative examination; the
      Lachman test, 25.0 (95% CI, 2.7-651.0) and 0.1 (95% CI, 0.0-0.4); and the
      composite assessment, 25.0 (95% CI, 2.1-306.0) and 0.04 (95% CI, 0.01-0.48),
      respectively. The LRs could not be generated for any specific examination
      maneuver for a posterior cruciate ligament tear, but the composite assessment had
      an LR of 21.0 (95% CI, 2.1-205.0) for a positive examination and 0.05 (95% CI,
      0.01-0.50) for a negative examination. Determination of meniscal lesions, using
      McMurray test, had an LR of 1.3 (95% CI, 0.9-1.7) for a positive examination and
      0.8 (95% CI, 0.6-1.1) for a negative examination; joint line tenderness, 0.9 (95%
      CI, 0.8-1.0) and 1.1 (95% CI, 1.0-1.3); and the composite assessment, 2.7 (95%
      CI, 1.4-5.1) and 0.4 (95% CI, 0.2-0.7), respectively. CONCLUSION: The composite
      examination for specific meniscal or ligamentous injuries of the knee performed
      much better than specific maneuvers, suggesting that synthesis of a group of
      examination maneuvers and historical items may be required for adequate
      diagnosis.

PMID- 11585486
TI  - Depression in patients recovering from a myocardial infarction.
AB  - Depression is common among patients recovering from a myocardial infarction (MI).
      Approximately 1 in 6 patients with MI experience major depression and at least
      twice as many as that have significant symptoms of depression soon after the
      event. Post-MI depression is an independent risk factor for increased mortality.
      Although the mechanism responsible for this association has not yet been defined,
      depression is clearly associated with poor compliance with risk-reducing
      recommendations, with abnormalities in autonomic tone that may make patients more
      susceptible to ventricular arrhythmias, and with increased platelet activation.
      Coronary revascularization procedures also appear to be used less often in those
      with post-MI depression than in comparable patients without mood disorder.
      Ongoing research will address whether treating depression improves prognosis.
      Until this question is answered, efforts should focus on enhancing adherence to
      treatment regimens in this group of patients, who are clearly at risk for
      noncompliance. Cardiac rehabilitation programs and increasing levels of social
      support may help improve symptoms and should be recommended to all patients.
      Treatment of depression itself should be individualized until safety and efficacy
      are determined for antidepressant therapy in patients who recently have had an
      MI.

PMID- 11585487
TI  - Antenatal corticosteroids-too much of a good thing?

PMID- 11585488
TI  - Graduated driver licensing systems: reducing crashes among teenage drivers.

PMID- 11585490
TI  - msJAMA. Genetics and preventive medicine: a time for inquiry.

PMID- 11585491
TI  - msJAMA. The role of genomics in public health and disease prevention.

PMID- 11585492
TI  - msJAMA. The genetics of sudden death.

PMID- 11585493
TI  - msJAMA. Genomics in medicine and public health: role of cost-effectiveness
      analysis.

PMID- 11585494
TI  - msJAMA. Genomic medicine: managing the complexity.

PMID- 11585499
TI  - Robotically assisted laparoscopic cholecystectomy: a pilot study.
AB  - HYPOTHESIS: Since the advent of laparoscopic surgery in 1987 and the introduction
      of robotics into medicine in 1991, medical technology has advanced to robotic
      applications in performing surgery. In our study, we investigated the feasibility
      of performing simple laparoscopic maneuvers and laparoscopic cholecystectomy
      using a robotic surgical system. DESIGN: The study used a ZEUS robotic system
      (Computer Motion Inc, Goleta, Calif), consisting of 3 interactive robotic arms
      fixed at the operating table and remotely controlled by the surgeon. After
      initial training, using a bench model and 3 isolated porcine livers to perform
      cholecystectomy, 7 female pigs underwent robotically assisted laparoscopic
      cholecystectomy. The surgeon, seated at the console, manipulated the 3-mm
      laparoscopic instruments and performed the surgery. RESULTS: Robotically assisted
      laparoscopic cholecystectomy was accomplished in all 7 pigs, with a mean
      operative time of 46 minutes (range, 30-62 minutes). There were no complications.
      The mean time to setup of the robotic system decreased from 30 minutes to 14
      minutes. All the robotic maneuvers were performed without any particular
      difficulties, and the movements were stable, accurate, and reliable, with good
      control. CONCLUSIONS: Our preliminary experimental study showed that robotically
      reproduced laparoscopic maneuvers, such as tying, suturing, dissection, clipping,
      and cautery, seemed to be as accurate and as fast as maneuvers made without
      robotics. We conclude that our initial experimental and animal study confirmed
      the feasibility of robotically assisted laparoscopic cholecystectomy. Further
      reports are needed to show that robotics can be used for clinical applications in
      surgery.

PMID- 11585500
TI  - What are the primary concerns of recently graduated surgeons and how do they
      differ from those of the residency training years?
AB  - HYPOTHESIS: Graduated surgeons have differences in concerns when comparisons are
      made between fellows and practicing surgeons, practicing surgeons and residents,
      and male and female surgeons. DESIGN AND SETTING: A survey was distributed to
      surgeons who graduated from 17 New England residency programs from 1993 to 1996,
      consisting of 9 demographic questions and 33 items coded on a Likert-type scale
      (with scores from 1 [least concerning] to 5 [most concerning]). PARTICIPANTS:
      Surgical fellows and practicing surgeons recently graduated from general surgical
      residency programs in New England who had participated in a previous study as
      residents. INTERVENTION: Distribution and completion of the survey. MAIN OUTCOME
      MEASURE: Personal and career-oriented concerns of recently graduated surgical
      residents. RESULTS: Personal issues continue to rank high for graduated
      residents, but the areas of greatest concern became more financially and career
      oriented. The top concerns of fellows were personal finances (mean score, 3.2),
      child rearing (mean score, 3.1), salary (mean score, 3.1), postponing family
      plans (mean score, 3.0), availability of role models (mean score, 2.9), and
      number of work hours (mean score, 2.8). The top concerns of practicing surgeons
      were salary (mean score, 3.2), personal finances (mean score, 3.1), number of
      referrals (mean score, 3.0), support for research (mean score, 2.7), child
      rearing (mean score, 2.7), and availability of role models (mean score, 2.7).
      Differences existed between men and women for child rearing, initiating personal
      relationships, maintaining personal relationships, maternity leave, and
      promotional advancement. Women were more concerned than men. CONCLUSIONS:
      Assistance with career planning and job selection during the residency years
      should be enhanced to diminish the concerns about financial issues and the
      availability of role models after graduation. Many of the concerns among male and
      female graduates are still reflective of larger societal expectations, but some,
      such as promotional advancement, may be attenuated through guidance and mentoring
      of residents before job selection.

PMID- 11585501
TI  - Experiences in thoracoscopic sympathectomy for axillary hyperhidrosis and
      osmidrosis: focusing on the extent of sympathectomy.
AB  - HYPOTHESIS: A more selective sympathectomy can improve the outcome of axillary
      hyperhidrosis and osmidrosis and minimize the potential sequelae. DESIGN:
      Retrospective cohort. SETTING: Tertiary care center. PATIENTS: Between July 1,
      1996, and May 30, 2000, 171 patients with axillary hyperhidrosis and osmidrosis
      were studied. INTERVENTIONS: T3-4 sympathectomies were performed in 40 patients
      (group 1), T4 sympathectomies were performed in 56 patients (group 2), and T4-5
      sympathectomies were performed in 75 patients (group 3). MAIN OUTCOME MEASURES:
      The surgical outcomes were evaluated by direct patient interview in the
      outpatient clinic or by telephone or mail questionnaires. The results were
      categorized as excellent (significant or complete disappearance of symptoms),
      good (>/=50% improvement), or poor (<50% improvement). RESULTS: There were no
      surgical mortalities in this study. Twenty-eight group 1 patients (70%), 16 group
      2 patients (29%), and 22 group 3 patients (29%) developed compensatory
      perspiration (P<.001). Six group 1 patients (15%), 1 group 2 patient (2%), and 1
      group 3 patient (1%) developed dry hands (P =.02). In the group 1 patients, the
      surgical outcomes were excellent in 21 (52%), good in 6 (15%), and poor in 13
      (32%). In the group 2 patients, the surgical outcomes were excellent in 29 (52%),
      good in 10 (18%), and poor in 17 (30%). In the group 3 patients, the surgical
      outcomes were excellent in 53 (71%), good in 11 (15%), and poor in 11(15%) (P
      =.04). (Percentages may not sum to 100 because of rounding.) CONCLUSION: T4-5
      sympathectomies provide higher patient satisfaction rates in treating axillary
      hyperhidrosis and osmidrosis, with fewer sequelae.

PMID- 11585502
TI  - Hypotension, hypoxia, and head injury: frequency, duration, and consequences.
AB  - BACKGROUND: Retrospective studies have suggested an association between systemic
      hypotension and hypoxia and worsened outcome from traumatic brain injury. Little
      is known, however, about the frequency and duration of these potentially
      preventable causes of secondary brain injury. HYPOTHESIS: Early episodes of
      hypoxia and hypotension occurring during initial resuscitation will have a
      significant impact on outcome following traumatic brain injury. DESIGN:
      Prospective cohort study. SETTING: Urban level I trauma center. PATIENTS:
      Patients with a traumatic brain injury who had a Glasgow Coma Score of 12 or less
      within the first 24 hours of admission to the hospital and computed tomographic
      scan results demonstrating intracranial pathologic features. Patients who died in
      the emergency department were excluded from the study. MAIN OUTCOME MEASURES:
      Automated blood pressure and pulse oximetry readings were collected prospectively
      from the time of arrival through initial resuscitation. The number and duration
      of hypotensive (systolic blood pressure, < or =90 mm Hg) and hypoxic (oxygen
      saturation, < or =92%) events were analyzed for their association with mortality
      and neurological outcome. RESULTS: One hundred seven patients met the enrollment
      criteria (median Glasgow Coma Score, 7). Overall mortality was 43%. Twenty-six
      patients (24%) had hypotension while in the emergency department, with an average
      of 1.5 episodes per patient (mean duration, 9.1 minutes). Of these 26 patients
      with hypotension, 17 (65%) died (P =.01). When the number of hypotensive episodes
      increased from 1 to 2 or more, the odds ratio for death increased from 2.1 to
      8.1. Forty-one patients (38%) had hypoxia, with an average of 2.1 episodes per
      patient (mean duration, 8.7 minutes). Of these 41 patients with hypoxia, 18 (44%)
      died (P =.68). CONCLUSIONS: Hypotension, but not hypoxia, occurring in the
      initial phase of resuscitation is significantly (P =.009) associated with
      increased mortality following brain injury, even when episodes are relatively
      short. These prospective data reinforce the need for early continuous monitoring
      and improved treatment of hypotension in brain-injured patients.

PMID- 11585503
TI  - Association of decreased perfusion of the ileoanal pouch mucosa with early
      postoperative pouchitis and local septic complications.
AB  - BACKGROUND: After ileoanal pouch operation, 5% to 40% of patients with ulcerative
      colitis and 2% to 8% of patients with familial adenomatous polyposis develop
      pouchitis. Seven percent to 32% of all patients have local septic complications.
      Pouch ischemia is discussed as a pathophysiologic factor. Tonometry is a
      minimally invasive method for estimating intramucosal pH (pHi), with a decreased
      pHi showing intramucosal acidosis characteristic of hypoperfusion. HYPOTHESIS:
      Decreased perfusion of the iloanal pouch measured by pHi is associated with local
      septic complications and the development of pouchitis. DESIGN: Prospective cohort
      study. SETTING: Surgical department of a university hospital. PATIENTS AND
      METHODS: The pHi in the ileoanal pouch of 98 patients was measured directly after
      the pouch procedure and correlated to the clinical course. Endoscopic examination
      of the pouch with biopsy and blinded histologic assessment, including calculation
      of a histologic pouchitis score, were routinely performed 3 months
      postoperatively. MAIN OUTCOME MEASURES: Development of pouchitis and local septic
      complications in correlation to pHi. RESULTS: A decreased pHi was statistically
      significantly associated with the development of pouchitis and the rate of local
      septic complications. All 3 patients with anastomotic stenosis had a pHi less
      than 7.00. The diagnosis of ulcerative colitis just failed in statistical
      significance as a risk factor for pouchitis. An increased body mass index just
      failed as a statistically significant risk factor for complications but was a
      risk factor for the development of acute pouchitis. CONCLUSION: Pouch
      hypoperfusion is a risk factor for the development of pouchitis and local septic
      complications.

PMID- 11585504
TI  - Value of digital exploration for diagnosing injuries to the left side of the
      diaphragm caused by stab wounds.
AB  - HYPOTHESIS: The digital exploration of stab wounds in the left thoracoabdominal
      region allows the early diagnosis of diaphragmatic lesions. DESIGN: Diagnostic
      test study. The digital exploration of the diaphragm was compared with laparotomy
      (the gold standard) and thoracoscopy. SETTING: The study setting was the Hospital
      Universitario San Vicente de Paul (Medellin, Colombia). This is a referral trauma
      center for the general community. PATIENTS: The study included 82 consecutive
      patients who were admitted to our institution during a 12-month period with
      injuries caused by stab wounds to the left thoracoabdominal region and who did
      not have indications for immediate surgery. Digital exploration of the wound was
      performed by the attending surgeon in the emergency department. If a lesion of
      the diaphragm was identified, a laparotomy was performed; if no diaphragmatic
      lesion was found, a diagnostic left thoracoscopy and/or laparotomy was performed.
      Results of the laparotomy (n = 63) or thoracoscopy (n = 19) were used as the
      standard of reference for the determination of sensitivity, specificity, and
      predictive values of digital exploration. INTERVENTION: The integrity of the
      diaphragm was determined by digital exploration through the stab wound. MAIN
      OUTCOME MEASURES: Sensitivity, specificity, predictive value, and likelihood
      ratio were calculated. RESULTS: For the detection of diaphragmatic lesions,
      digital exploration demonstrated a sensitivity of 96%, a specificity of 83.3%, a
      positive predictive value of 91%, and a negative predictive value of 93.7%.
      CONCLUSION: Digital exploration is a reliable method for the detection of
      injuries to the left side of the diaphragm caused by stab wounds.

PMID- 11585505
TI  - Detection of pinpoint tenderness on the appendix under ultrasonography is useful
      to confirm acute appendicitis.
AB  - HYPOTHESIS: Ultrasonography can be efficiently performed using new criteria for
      the diagnosis of acute appendicitis. DESIGN: Prospective trial. PATIENTS: Eighty
      nine patients admitted to the hospital with suspected appendicitis between March
      1998 and November 2000. INTERVENTION: At hospital admission, a staff surgeon
      evaluated each patient and determined whether the patient had appendicitis
      requiring immediate surgery or another disease. Patients then underwent
      ultrasonography. A sonographic transducer was placed on the area of maximal
      tenderness. When the pathological manifestation was depicted, the examiner
      slipped a fingertip between the transducer and the patient's skin and then
      pressed the area of depicted pathological manifestation to find pinpoint
      tenderness. When maximal pinpoint tenderness was noted on the appendix or on
      pathological manifestations contiguous to the appendix, we diagnosed the
      condition as appendicitis. MAIN OUTCOME MEASURES: Sensitivity, specificity,
      positive and negative predictive values, and overall accuracy. RESULTS: The
      diagnosis of appendicitis by this criteria had a sensitivity of 86.7%, a
      specificity of 89.7%, a positive predictive value of 94.5%, a negative predictive
      value of 76.5%, and overall accuracy of 87.6%. All 50 patients with pinpoint
      tenderness noted on the appendix had appendicitis. The surgeon's initial clinical
      impression had a sensitivity of 83.3%, a specificity of 44.8%, a positive
      predictive value of 75.8%, a negative predictive value of 56.5%, and overall
      accuracy of 70.8%. CONCLUSIONS: The efficacy of ultrasonography using the simple
      criteria was superior to that of the surgeon's initial clinical impression
      (P<.001). Our ultrasonographic criteria for the diagnosis of appendicitis are
      simple to use and efficient.

PMID- 11585506
TI  - A 9-year experience with 126 pancreas transplants with portal enteric drainage.
AB  - HYPOTHESIS: A novel technique of pancreas transplantation (PTX) with portal
      venous delivery of insulin and enteric exocrine drainage (portal enteric) was
      developed at our center to improve the PTX procedure. DESIGN: Case series.
      SETTING: Single-center experience at a university hospital. PATIENTS AND
      INTERVENTION: From October 1990 through December 1999, we performed 126 PTXs with
      portal enteric drainage, including 90 simultaneous kidney PTXs (SKPT) and 36
      solitary PTXs (18 sequential PTXs after kidney transplantation and 18 PTXs
      alone). MAIN OUTCOME MEASURES: Patient and graft survival rates; medical and
      surgical morbidity. Three groups, representing 3 eras of immunosuppression, were
      compared. Thirty patients underwent SKPT with muromonab-CD3 induction and
      cyclosporine-based therapy in era 1 (October 1990 through June 1995); 42 SKPTs
      received tacrolimus and mycophenolate mofetil-based immunosuppression without
      antibody induction in era 2 (July 1995 through May 1998); and 18 SKPTs were
      performed in era 3 (June 1998 through December 1999) with either basiliximab or
      daclizumab induction. RESULTS: One-year patient survival rates after SKPT were
      77% in era 1, 93% in era 2, and 100% in era 3 (P =.03). The 1-year kidney graft
      survival rates were 77% in era 1, 93% in era 2, and 94% in era 3 (P =.08). The 1
      year pancreas graft survival rates after SKPT were 60% in era 1, 83% in era 2,
      and 83% in era 3 (P =.06). The incidences of rejection (63% vs. 33% vs. 39%;
      P<.001) and thrombosis (20% vs. 7% vs. 6%; P<.001) were decreased in eras 2 and
      3. CONCLUSION: Simultaneous kidney PTXs with portal enteric drainage can be
      performed with improved outcomes.

PMID- 11585507
TI  - Predictive factors for unanticipated admissions after ambulatory laparoscopic
      cholecystectomy.
AB  - HYPOTHESIS: Analysis of the causes of unanticipated admission after ambulatory
      laparoscopic cholecystectomy may permit the identification of predictive clinical
      factors for postoperative admission. DESIGN: Univariate and multivariate analyses
      of clinical variables associated with unplanned admission in a retrospective case
      control series of ambulatory laparoscopic cholecystectomies. SETTING: A major
      university-affiliated teaching hospital. PATIENTS: Seven hundred thirty-one
      consecutive patients who underwent ambulatory laparoscopic cholecystectomies
      between January 1, 1996, and December 31, 1999. INTERVENTION: Ambulatory
      laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: Unplanned postoperative
      admissions. Univariate and multivariate analyses of 19 clinicopathologic factors
      were performed to identify independent predictive factors for these admissions.
      RESULTS: Seven hundred six patients were discharged on the day of operation. The
      remaining 25 required admission because of pain (n = 10), nausea and vomiting (n
      = 6), retention of urine (n = 5), patient preference (n = 3), and medical
      observation (n = 1), giving an unanticipated admission rate of 3.4%. Significant
      factors associated with unplanned admission included operative duration of longer
      than 60 minutes and thickened gallbladder wall on ultrasonographic and
      pathological findings. By means of logistic regression, length of operation was
      the only independent predictive factor. Operative time exceeding 60 minutes
      incurred a 4-fold increased risk for unanticipated admission. CONCLUSIONS:
      Operative duration was the best predictive factor for unplanned admission after
      ambulatory laparoscopic cholecystectomy. During selection of patients for day
      surgery, ultrasonographic demonstration of a thickened gallbladder wall should be
      taken into consideration.

PMID- 11585508
TI  - Reduction in recurrence risk for involved or inadequate margins with edge
      cryotherapy after liver resection for colorectal metastases.
AB  - HYPOTHESIS: The usefulness of additional edge cryotherapy after liver resection
      for liver metastases from colorectal cancer to improve involved or inadequate
      (less than 1 cm) margins is uncertain. DESIGN: Retrospective analysis of
      prospectively collected data. SETTING: Department of surgery at a university
      hospital. PATIENTS: Eighty-six consecutive patients with hepatic metastases from
      colorectal cancer in whom we applied additional edge cryotherapy to involved or
      inadequate margins. This group was compared with 134 patients who underwent
      resection without edge cryotherapy (control group) during the same period.
      INTERVENTION: Potentially curative treatment was achieved by adding edge
      cryotherapy to insufficient resection sites in patients not eligible for further
      resection. MAIN OUTCOME MEASURES: Edge recurrence rate in the study group;
      validation of an additional treatment to improve curative resectability; and
      comparison of morbidity and local recurrence rates with the control group.
      RESULTS: At a median follow-up of 39 months, 47 patients were alive and 39 had
      died. Local recurrence at the resection site was diagnosed in 9 patients (10%),
      of which 7 occurred in patients with involved margins and 2 in patients with
      resection margin less than 1 cm. Thirty-six patients (42%) experienced recurrence
      in the remnant liver. Extrahepatic recurrence occurred in 38 patients (44%), the
      lungs being the most common site (22 patients [26%]). CONCLUSIONS: Edge
      cryotherapy is a potent additional surgical treatment option in patients with
      liver metastases from colorectal cancer. The percentage of patients who can be
      treated for cure can be increased, especially if complex liver surgery is
      demanded.

PMID- 11585509
TI  - Attenuation of vascular endothelial dysfunction by testosterone receptor blockade
      after trauma and hemorrhagic shock.
AB  - HYPOTHESIS: The salutary effects of the testosterone receptor antagonist
      flutamide on the depressed immune and cardiovascular functions after hemorrhage
      and resuscitation are related to improved endothelial cell function, which can
      subsequently lead to an increase in organ blood flow, oxygen delivery, and tissue
      oxygen consumption. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Male adult
      rats underwent a 5-cm midline laparotomy (ie, trauma) and were bled to and
      maintained at a mean systemic arterial pressure of 40 mm Hg until 40% maximal
      blood-out volume was returned in the form of Ringer lactate). The animals were
      then resuscitated with 4 times the total volume of shed blood with Ringer lactate
      for 60 minutes. Flutamide (25 mg/kg) or an equivalent volume of the vehicle
      propanediol was injected subcutaneously 15 minutes before the end of
      resuscitation. At 20 hours after resuscitation, aortic rings (approximately 2.5
      mm in length) were isolated and mounted in an organ chamber. Dose responses for
      an endothelium-dependent vasodilator (acetylcholine chloride) and endothelium
      independent vasodilator (nitroglycerine) were determined. Organ blood flow was
      measured using strontium 85-labeled microspheres. Total hemoglobin and oxygen
      content in the femoral artery and portal, hepatic, and renal veins were
      determined. Oxygen delivery and consumption in liver, small intestine, and
      kidneys were calculated. RESULTS: Administration of flutamide after trauma
      hemorrhage attenuated the depressed endothelial function. Furthermore, flutamide
      treatment restored the reduced blood flow and oxygen delivery and consumption in
      all organs tested after trauma-hemorrhage and resuscitation. CONCLUSION:
      Flutamide appears to be a useful adjunct for improving vascular endothelial
      function and regional hemodynamics after trauma-hemorrhage and resuscitation.

PMID- 11585510
TI  - Surgical management of carcinoma of the hypopharynx and cervical esophagus:
      analysis of 209 cases.
AB  - BACKGROUND: Free jejunal transfer has become the standard technique for
      reconstruction of the pharynx and hypopharynx, especially with proximal
      neoplastic lesions, whereas gastric tube interposition is the technique of choice
      for reconstruction of the hypopharynx and cervical esophagus when resection
      extends below the thoracic inlet. HYPOTHESIS: Surgical ablation is a viable
      option for advanced hypopharyngeal and cervical esophageal neoplasms, with
      stomach interposition a safe and preferred method of reconstruction. DESIGN:
      Retrospective analysis. SETTING: University hospital that is a regional referral
      institution for esophageal cancer treatment and complex digestive reconstructions
      after esophagectomy. PATIENTS: We reviewed the records of 209 patients who
      underwent total pharyngolaryngectomy between May 1982 and July 1999. The majority
      of patients had advanced cancer: hypopharyngeal in 131 cases and cervical
      esophageal in 78 cases. INTERVENTIONS: Pharyngolaryngectomy and total
      esophagectomy with pharyngogastric anastomoses (n = 127); pharyngolaryngectomy,
      cervical esophagectomy, and reconstruction with free jejunal transplant (n = 77);
      and pharyngolaryngectomy and total esophagectomy with pharyngocolic anastomoses
      (n = 5). MAIN OUTCOME MEASURES: Postoperative mortality and morbidity, long-term
      survival, and prognostic factors influencing survival. RESULTS: The postoperative
      in-hospital mortality rate was 4.8% (10 patients), with a postoperative morbidity
      rate of 38.3%. Alimentary continuity was achieved using the stomach (127
      patients), colon (5 patients), or free jejunal autograft (77 patients). The 1
      year and 5-year survival rates were 62% and 24%, respectively. There was no
      significant difference with regard to the survival between gastric transposition
      and free jejunal autograft, but there were fewer complications in the gastric
      pull-up group (33% vs 47%, P<.05). The significant adverse factors affecting
      survival were tumor cervical localization, postoperative complications, disease
      stages pT3 and pT4 for the cervical esophageal tumors, microscopic pharyngeal
      penetration, or incomplete resection. The significant beneficial factors were
      tumor hypopharyngeal localization and postoperative radiotherapy. CONCLUSIONS:
      Surgical ablation is a viable option for advanced hypopharyngeal and cervical
      esophageal neoplasms, with stomach interposition the preferred method of
      reconstruction. Although the prognosis is poor, satisfactory short-term
      palliation can be achieved. The significant adverse factors affecting survival
      should be taken into account to select the candidates for surgery.

PMID- 11585511
TI  - Laparoscopic gastric banding in older patients.
AB  - HYPOTHESIS: Older patients experience the same benefits from a laparoscopic
      gastric banding (LGB) operation as younger patients. DESIGN: A case series of 320
      morbidly obese and superobese patients who underwent LGB within a 46-month
      period. SETTING: University Hospital Innsbruck, General Surgical Department,
      Innsbruck, Austria. PATIENTS: A consecutive sample of 320 patients who met the
      criteria for a bariatric procedure and were aged 18 years or older. Patients were
      divided into the following 2 age groups: younger patients (group A, 18-49 years)
      and older patients (group B, > or =50 years). INTERVENTION: Laparoscopic gastric
      banding with an adjustable gastric band. MAIN OUTCOME MEASURES: Clinicopathologic
      features, including weight loss, complications, length of hospital stay, and
      operative times, were reviewed retrospectively, and a multivariate analysis was
      carried out. RESULTS: Of 320 patients, we identified 68 older patients (21.5%,
      group B). The mean postoperative follow-up period was 12 months (range, 6-28
      months). The average preoperative weight was 127.8 kg (body mass index
      [calculated as weight in kilograms divided by the square of height in meters],
      44.29). The average total weight loss was 4.3 kg per month for the first 3
      months, reaching an average total of 31.0 kg after 1 year. The excess weight loss
      after 12 months was 68%. Complications requiring reoperation occurred in 10.3% of
      patients. Ninety-seven percent of the patients reported an improvement in their
      comorbid conditions. CONCLUSIONS: Older patients receive the same benefits from
      LGB as younger patients, with an acceptable postoperative complication rate.
      Presently, our upper age limit is 70 years.

PMID- 11585512
TI  - Preoperative and intraoperative predictors of postoperative morbidity, poor graft
      function, and early rejection in 190 patients undergoing liver transplantation.
AB  - HYPOTHESIS: Preoperative and intraoperative variables predict in part adverse
      outcome after liver transplantation. DESIGN: Prospective, blinded, cohort study.
      SETTING: Tertiary care hospital. SUBJECTS: A total of 190 adult patients
      undergoing primary liver transplantation. MAIN OUTCOME MEASURE: Adverse outcome
      was prospectively defined as either in-hospital death or prolonged postoperative
      hospitalization (>14 days) associated with morbidity. Potential preoperative and
      intraoperative risk factors were collected. Associations were tested by
      univariate analysis followed by multivariate analysis in which preoperative
      factors were entered before intraoperative factors. RESULTS: Adverse outcome
      occurred in 44.7% of patients. Incidences of other complications were as follows:
      in-hospital mortality (8.4%), primary graft nonfunction (4.2%), poor early graft
      function (1.1%), and early rejection (31.2%). Univariate predictors of adverse
      outcome were United Network for Organ Sharing status (P =.003), Child-Turcotte
      Pugh score (P =.02), POSSUM physiological score (P =.002), recipient age (P
      =.01), preoperative serum high-density lipoprotein cholesterol level (P =.03),
      preoperative serum creatinine level (P =.002), preoperative serum total IgG level
      (P =.004), duration in hospital preoperatively (P =.03), operative duration
      (P<.001), allogeneic erythrocyte transfusions (P<.001), total intraoperative
      fluids (P =.002), and use of inotropic agents (P =.01). In the final multivariate
      model, predictors of adverse outcome were United Network for Organ Sharing status
      (P =.03), recipient age (P =.002), and total intraoperative fluids (P =.04). Most
      patients who died or had a prolonged hospitalization exhibited dysfunction of
      more than 1 organ system, including pulmonary, renal, and infectious
      complications. CONCLUSIONS: Adverse outcome occurs frequently after liver
      transplantation, usually involves multiple organ systems, and is predicted in
      part by several preoperative and intraoperative factors.

PMID- 11585513
TI  - Bronchoscopic diagnosis of thyroid cancer with laryngotracheal invasion.
AB  - HYPOTHESIS: Some controversy exists concerning the appropriate surgical
      management for patients with thyroid cancer invading the laryngotracheal wall. We
      have used shaving of the wall when cancer invasion was confined to the
      perichondrium, and extensive resection when it invaded further. Preoperative
      assessment of the depth and length of laryngotracheal invasion is important when
      choosing an appropriate surgical procedure. DESIGN: Prospective study. SETTING: A
      Japanese center for thyroid diseases, where about 1400 thyroid operations are
      performed each year. PATIENTS: Of 171 patients with thyroid cancer who were
      surgically treated between January 1, 2000, and July 30, 2000, 37 were suspected
      to have laryngotracheal invasion on preoperative magnetic resonance imaging or
      ultrasonography. INTERVENTION: We used bronchoscopy to examine the 37 patients
      suspected to have laryngotracheal invasion. MAIN OUTCOME MEASURE: Bronchoscopic
      findings (localized mucosal redness, telangiectasia, mucosal elevation, mucosal
      edema, and mucosal erosion) were compared with pathological results in the 30
      patients who underwent curative resections. Seven patients were excluded because
      of palliative resections. RESULTS: Of the 18 patients without localized mucosal
      changes, we performed shaving of the laryngotracheal wall in 4 patients because
      we found laryngotracheal invasion during surgery. Shaving of the laryngotracheal
      wall was performed successfully in terms of obtaining a cancer-free margin.
      Twelve patients with localized mucosal redness required extensive resections.
      Other mucosal changes were found depending on the depth of cancer invasion.
      CONCLUSION: Surgeons should perform extensive resections when encountering
      localized mucosal redness on bronchoscopy.

PMID- 11585514
TI  - Mitochondrial perturbations and oxidant stress in lymphocytes from patients
      undergoing surgery and general anesthesia.
AB  - BACKGROUND: Previous studies have shown that a profound suppression of immune
      function transiently occurs in patients who undergo surgery under general
      anesthesia. The decline in the absolute counts of peripheral blood lymphocytes
      constitutes a major factor accounting for this immune defect, and recent evidence
      indicates that apoptosis plays a crucial role in determining postsurgical
      lymphocytopenia. HYPOTHESIS: An altered oxidation-reduction status of
      mitochondria may contribute through apoptosis to the loss of lymphocytes
      following surgical trauma and general anesthesia. DESIGN: We studied 16 patients
      with American Society of Anesthesiologists' physical status I or II who underwent
      elective surgery under general anesthesia. The data were collected prospectively.
      SETTING: University hospital. MAIN OUTCOME MEASURES: Samples of peripheral blood
      were drawn on the day before surgery and at 24 and 96 hours after the operation.
      Following lymphocyte isolation, the mitochondrial transmembrane potential was
      assessed by flow cytometry using 3,3'-dihexylocarbo-cyanine iodide, and stains
      with hydroethidine and 2'-7'-dichlorofluorescein diacetate were used to determine
      the generation of reactive oxygen species. The labeling of lymphocytes with
      monobromobimane was used to assess the presence of reduced glutathione. RESULTS:
      At 24 hours after surgery, we detected a significantly elevated frequency of
      peripheral blood lymphocytes (P =.002), which incorporated low levels of 3,3'
      dihexylocarbo-cyanine iodide, compared with the preoperative period. At this same
      time point, the frequency of lymphocytes with the hydroethidine- and 2'-7'
      dichlorofluorescein diacetate-positive phenotype was elevated compared with
      baseline levels. Conversely, at 24 hours after surgery, the frequency of cells
      that stained positive for glutathione was strongly decreased compared with
      preoperative values. Overall measurements returned to the baseline levels at 96
      hours after surgery. CONCLUSION: The strict association we observed between the
      overproduction of reactive oxygen species and the disruption of the mitochondrial
      transmembrane potential supports the view that alterations in mitochondrial
      energy metabolism, paralleled by the presence of a pro-oxidant oxidation
      reduction status, could be involved in the accelerated apoptotic loss of
      lymphocytes following surgical trauma and general anesthesia.

PMID- 11585515
TI  - Duct-to-duct biliary anastomosis in living related liver transplantation: the
      Paul Brousse technique.
AB  - Complications relating to the bile ducts are still the single most important
      technical cause of morbidity following living related liver transplantation. In
      living related liver transplantation, a single case (of more than 2000 reported
      cases) of biliary reconstruction by means of a duct-to-duct biliary anastomosis
      has been reported. The technique of duct-to-duct biliary anastomosis in living
      related liver transplantation is described herein. The technique can only be used
      when no tension is applied to the anastomosis and the cut ends of the bile ducts
      are clearly visible. A Roux-en-Y operation must be performed if these conditions
      are not fulfilled.

PMID- 11585516
TI  - Antioxidants in critical illness.
AB  - Oxidative stress has been implicated in the manifestations of critical illnesses,
      including ischemia and reperfusion injury and systemic inflammatory states. This
      review describes the evidence for increased oxidative stress in critically ill
      patients and explores the data regarding antioxidant therapy for these
      conditions. Antioxidant therapies reviewed include N-acetylcysteine, selenium,
      vitamins E and C, superoxide dismutase, catalase, lazaroids, and allopurinol. We
      focus on the results of these interventions in animal models and human trials,
      when available.

PMID- 11585517
TI  - Predicting severe pancreatitis.

PMID- 11585518
TI  - Image of the month. Eventration of the diaphragm.

PMID- 11585519
TI  - Moments in surgical history: Zabdiel Boylston and smallpox inoculation.

PMID- 11585520
TI  - West Nile virus: a reemerging global pathogen.

PMID- 11585521
TI  - Crow deaths as a sentinel surveillance system for West Nile virus in the
      northeastern United States, 1999.
AB  - In addition to human encephalitis and meningitis cases, the West Nile (WN) virus
      outbreak in the summer and fall of 1999 in New York State resulted in bird deaths
      in New York, New Jersey, and Connecticut. From August to December 1999, 295 dead
      birds were laboratory-confirmed with WN virus infection; 262 (89%) were American
      Crows (Corvus brachyrhynchos). The New York State Department of Health received
      reports of 17,339 dead birds, including 5,697 (33%) crows; in Connecticut 1,040
      dead crows were reported. Bird deaths were critical in identifying WN virus as
      the cause of the human outbreak and defining its geographic and temporal limits.
      If established before a WN virus outbreak, a surveillance system based on bird
      deaths may provide a sensitive method of detecting WN virus.

PMID- 11585522
TI  - Serologic evidence for West Nile virus infection in birds in the New York City
      vicinity during an outbreak in 1999.
AB  - As part of an investigation of an encephalitis outbreak in New York City, we
      sampled 430 birds, representing 18 species in four orders, during September 13
      23, 1999, in Queens and surrounding counties. Overall, 33% were positive for West
      Nile (WN) virus-neutralizing antibodies, and 0.5% were positive for St. Louis
      encephalitis virus-neutralizing antibodies. By county, Queens had the most
      seropositive birds for WN virus (50%); species with the greatest seropositivity
      for WN virus (sample sizes were at least six) were Domestic Goose, Domestic
      Chicken, House Sparrow, Canada Goose, and Rock Dove. One sampled bird, a captive
      adult Domestic Goose, showed signs of illness; WN virus infection was confirmed.
      Our results support the concept that chickens and House Sparrows are good
      arbovirus sentinels. This study also implicates the House Sparrow as an important
      vertebrate reservoir host.

PMID- 11585523
TI  - West Nile virus isolates from mosquitoes in New York and New Jersey, 1999.
AB  - An outbreak of encephalitis due to West Nile (WN) virus occurred in New York City
      and the surrounding areas during 1999. Mosquitoes were collected as part of a
      comprehensive surveillance program implemented to monitor the outbreak. More than
      32,000 mosquitoes representing 24 species were tested, and 15 WN virus isolates
      were obtained. Molecular techniques were used to identify the species represented
      in the WN virus-positive mosquito pools. Most isolates were from pools containing
      Culex pipiens mosquitoes, but several pools contained two or more Culex species.

PMID- 11585524
TI  - Dead bird surveillance as an early warning system for West Nile virus.
AB  - As part of West Nile (WN) virus surveillance in New York State in 2000, 71,332
      ill or dead birds were reported; 17,571 (24.6%) of these were American Crows. Of
      3,976 dead birds tested, 1,263 (31.8%) were positive for WN virus. Viral activity
      was first confirmed in 60 of the state's 62 counties with WN virus-positive dead
      birds. Pathologic findings compatible with WN virus were seen in 1,576 birds
      (39.6% of those tested), of which 832 (52.8%) were positive for WN virus. Dead
      crow reports preceded confirmation of viral activity by several months, and WN
      virus-positive birds were found >3 months before the onset of human cases. Dead
      bird surveillance appears to be valuable for early detection of WN virus and for
      guiding public education and mosquito control efforts.

PMID- 11585525
TI  - West Nile virus surveillance in Connecticut in 2000: an intense epizootic without
      high risk for severe human disease.
AB  - In 1999, Connecticut was one of three states in which West Nile (WN) virus
      actively circulated prior to its recognition. In 2000, prospective surveillance
      was established, including monitoring bird deaths, testing dead crows, trapping
      and testing mosquitoes, testing horses and hospitalized humans with neurologic
      illness, and conducting a human seroprevalence survey. WN virus was first
      detected in a dead crow found on July 5 in Fairfield County. Ultimately, 1,095
      dead crows, 14 mosquito pools, 7 horses, and one mildly symptomatic person were
      documented with WN virus infection. None of 86 hospitalized persons with
      neurologic illness (meningitis, encephalitis, Guillain-Barre-like syndrome) and
      no person in the seroprevalence survey were infected. Spraying in response to
      positive surveillance findings was minimal. An intense epizootic of WN virus can
      occur without having an outbreak of severe human disease in the absence of
      emergency adult mosquito management.

PMID- 11585526
TI  - Mosquito surveillance and polymerase chain reaction detection of West Nile virus,
      New York State.
AB  - West Nile (WN) virus was detected in the metropolitan New York City (NYC) area
      during the summer and fall of 1999. Sixty-two human cases, 7 fatal, were
      documented. The New York State Department of Health initiated a departmental
      effort to implement a statewide mosquito and virus surveillance system. During
      the 2000 arbovirus surveillance season, we collected 317,676 mosquitoes,
      submitted 9,952 pools for virus testing, and detected 363 WN virus-positive pools
      by polymerase chain reaction (PCR). Eight species of mosquitoes were found
      infected. Our mosquito surveillance system complemented other surveillance
      systems in the state to identify relative risk for human exposure to WN virus.
      PCR WN virus-positive mosquitoes were detected in NYC and six counties in the
      lower Hudson River Valley and metropolitan NYC area. Collective surveillance
      activities suggest that WN virus can disperse throughout the state and may impact
      local health jurisdictions in the state in future years.

PMID- 11585527
TI  - Partial genetic characterization of West Nile virus strains, New York State,
      2000.
AB  - We analyzed nucleotide sequences from the envelope gene of 11 West Nile (WN)
      virus strains collected in New York State during the 2000 transmission season to
      determine whether they differed genetically from each other and from the initial
      strain isolated in 1999. The complete envelope genes of these strains were
      amplified by reverse transcription-polymerase chain reaction. The resulting
      sequences were aligned, the genetic distances were computed, and a phylogenetic
      tree was constructed. Ten (0.7%) of 1,503 positions in the envelope gene were
      polymorphic in one or more sequences. The genetic distances were 0.003 or less.
      WN virus strains circulating in 2000 were homogeneous with respect to one another
      and to a strain isolated in 1999.

PMID- 11585528
TI  - West Nile encephalitis in Israel, 1999: the New York connection.
AB  - We describe two cases of West Nile (WN) encephalitis in a married couple in Tel
      Aviv, Israel, in 1999. Reverse transcription-polymerase chain reaction performed
      on a brain specimen from the husband detected a WN viral strain nearly identical
      to avian strains recovered in Israel in 1998 (99.9% genomic sequence homology)
      and in New York in 1999 (99.8%). This result supports the hypothesis that the
      1999 WN virus epidemic in the United States originated from the introduction of a
      strain that had been circulating in Israel.

PMID- 11585529
TI  - Dead crow densities and human cases of West Nile virus, New York State, 2000.
AB  - In 2000, Staten Island, New York, reported 10 human West Nile virus cases and
      high densities of dead crows. Surrounding counties with <2 human cases had
      moderate dead crow densities, and upstate counties with no human cases had low
      dead crow densities. Monitoring such densities may be helpful because this factor
      may be determined without the delays associated with specimen collection and
      testing.

PMID- 11585530
TI  - Mosquito surveillance for West Nile virus in Connecticut, 2000: isolation from
      Culex pipiens, Cx. restuans, Cx. salinarius, and Culiseta melanura.
AB  - Fourteen isolations of West Nile (WN) virus were obtained from four mosquito
      species (Culex pipiens [5], Cx. restuans [4], Cx. salinarius [2], and Culiseta
      melanura [3]) in statewide surveillance conducted from June through October 2000.
      Most isolates were obtained from mosquitoes collected in densely populated
      residential locales in Fairfield and New Haven counties, where the highest rates
      of dead crow sightings were reported and where WN virus was detected in 1999.
      Minimum field infection rates per 1,000 mosquitoes ranged from 0.5 to 1.8 (county
      based) and from 1.3 to 76.9 (site specific). Cx. restuans appears to be important
      in initiating WN virus transmission among birds in early summer; Cx. pipiens
      appears to play a greater role in amplifying virus later in the season. Cs.
      melanura could be important in the circulation of WN virus among birds in sylvan
      environments; Cx. salinarius is a suspected vector of WN virus to humans and
      horses.

PMID- 11585531
TI  - Clinical characteristics of the West Nile fever outbreak, Israel, 2000.
AB  - West Nile (WN) virus is endemic in Israel. The last reported outbreak had
      occurred in 1981. From August to October 2000, a large-scale epidemic of WN fever
      occurred in Israel; 417 cases were confirmed, with 326 hospitalizations. The main
      clinical presentations were encephalitis (57.9%), febrile disease (24.4%), and
      meningitis (15.9%). Within the study group, 33 (14.1%) hospitalized patients
      died. Mortality was higher among patients >70 years (29.3%). On multivariate
      regressional analysis, independent predictors of death were age >70 years (odds
      ratio [OR] 7.7), change in level of consciousness (OR 9.0), and anemia (OR 2.7).
      In contrast to prior reports, WN fever appears to be a severe illness with high
      rate of central nervous system involvement and a particularly grim outcome in the
      elderly.

PMID- 11585532
TI  - West Nile virus infection in birds and mosquitoes, New York State, 2000.
AB  - West Nile (WN) virus was found throughout New York State in 2000, with the
      epicenter in New York City and surrounding counties. We tested 3,403 dead birds
      and 9,954 mosquito pools for WN virus during the transmission season. Sixty-three
      avian species, representing 30 families and 14 orders, tested positive for WN
      virus. The highest proportion of dead birds that tested positive for WN virus was
      in American Crows in the epicenter (67% positive, n=907). Eight mosquito species,
      representing four genera, were positive for WN virus. The minimum infection rate
      per 1,000 mosquitoes (MIR) was highest for Culex pipiens in the epicenter: 3.53
      for the entire season and 7.49 for the peak week of August 13. Staten Island had
      the highest MIR (11.42 for Cx. pipiens), which was associated with the highest
      proportion of dead American Crows that tested positive for WN virus (92%, n=48)
      and the highest number of human cases (n=10).

PMID- 11585533
TI  - West Nile fever outbreak, Israel, 2000: epidemiologic aspects.
AB  - From August 1 to October 31, 2000, 417 cases of West Nile (WN) fever were
      serologically confirmed throughout Israel; 326 (78%) were hospitalized patients.
      Cases were distributed throughout the country; the highest incidence was in
      central Israel, the most populated part. Men and women were equally affected, and
      their mean age was 54+/-23.8 years (range 6 months to 95 years). Incidence per
      1,000 population increased from 0.01 in the 1st decade of life to 0.87 in the 9th
      decade. There were 35 deaths (case-fatality rate 8.4%), all in patients >50 years
      of age. Age-specific case-fatality rate increased with age. Central nervous
      system involvement occurred in 170 (73%) of 233 hospitalized patients. The
      countrywide spread, number of hospitalizations, severity of the disease, and high
      death rate contrast with previously reported outbreaks in Israel.

PMID- 11585534
TI  - West Nile outbreak in horses in southern France, 2000: the return after 35 years.
AB  - On September 6, 2000, two cases of equine encephalitis caused by West Nile (WN)
      virus were reported in southern France (Herault Province), near Camargue National
      Park, where a WN outbreak occurred in 1962. Through November 30, 76 cases were
      laboratory confirmed among 131 equines with neurologic disorders. The last
      confirmed case was on November 3, 2000. All but three cases were located in a
      region nicknamed "la petite Camargue," which has several large marshes, numerous
      colonies of migratory and resident birds, and large mosquito populations. No
      human case has been confirmed among clinically suspected patients, nor have
      abnormal deaths of birds been reported. A serosurvey has been undertaken in
      horses in the infected area, and other studies are in progress.

PMID- 11585535
TI  - The relationships between West Nile and Kunjin viruses.
AB  - Until recently, West Nile (WN) and Kunjin (KUN) viruses were classified as
      distinct types in the Flavivirus genus. However, genetic and antigenic studies on
      isolates of these two viruses indicate that the relationship between them is more
      complex. To better define this relationship, we performed sequence analyses on 32
      isolates of KUN virus and 28 isolates of WN virus from different geographic
      areas, including a WN isolate from the recent outbreak in New York. Sequence
      comparisons showed that the KUN virus isolates from Australia were tightly
      grouped but that the WN virus isolates exhibited substantial divergence and could
      be differentiated into four distinct groups. KUN virus isolates from Australia
      were antigenically homologous and distinct from the WN isolates and a Malaysian
      KUN virus. Our results suggest that KUN and WN viruses comprise a group of
      closely related viruses that can be differentiated into subgroups on the basis of
      genetic and antigenic analyses.

PMID- 11585536
TI  - Rapid determination of HLA B*07 ligands from the West Nile virus NY99 genome.
AB  - Defined T cell epitopes for West Nile (WN) virus may be useful for developing
      subunit vaccines against WN virus infection and diagnostic reagents to detect WN
      virus-specific immune response. We applied a bioinformatics (EpiMatrix) approach
      to search the WN virus NY99 genome for HLA B*07 restricted cytotoxic T cell (CTL)
      epitopes. Ninety-five of 3,433 WN virus peptides scored above a predetermined
      cutoff, suggesting that these would be likely to bind to HLA B*07 and would also
      be likely candidate CTL epitopes. Compared with other methods for genome mapping,
      derivation of these ligands was rapid and inexpensive. Major histocompatibility
      complex ligands identified by this method may be used to screen T cells from WN
      virus-exposed persons for cell-mediated response to WN virus or to develop
      diagnostic reagents for immunopathogenesis studies and epidemiologic
      surveillance.

PMID- 11585537
TI  - West Nile virus infection in the golden hamster (Mesocricetus auratus): a model
      for West Nile encephalitis.
AB  - This report describes a new hamster model for West Nile (WN) virus encephalitis.
      Following intraperitoneal inoculation of a New York isolate of WN virus, hamsters
      had moderate viremia of 5 to 6 days in duration, followed by the development of
      humoral antibodies. Encephalitic symptoms began 6 days after infection; about
      half the animals died between the seventh and 14th days. The appearance of viral
      antigen in the brain and neuronal degeneration also began on the sixth day. WN
      virus was cultured from the brains of convalescent hamsters up to 53 days after
      initial infection, suggesting that persistent virus infection occurs. Hamsters
      offer an inexpensive model for studying the pathogenesis and treatment of WN
      virus encephalitis.

PMID- 11585538
TI  - Experimental infection of chickens as candidate sentinels for West Nile virus.
AB  - We evaluated the susceptibility, duration and intensity of viremia, and serologic
      responses of chickens to West Nile (WN) virus (WNV-NY99) infection by needle,
      mosquito, or oral inoculation. None of 21 infected chickens developed clinical
      disease, and all these developed neutralizing antibodies. Although viremias were
      detectable in all but one chicken, the magnitude (mean peak viremia <10,000
      PFU/mL) was deemed insufficient to infect vector mosquitoes. WNV-NY99 was
      detected in cloacal and/or throat swabs from 13 of these chickens, and direct
      transmission of WNV-NY99 between chickens occurred once (in 16 trials), from a
      needle-inoculated bird. Nine chickens that ingested WNV-NY99 failed to become
      infected. The domestic chickens in this study were susceptible to WN virus
      infection, developed detectable antibodies, survived infection, and with one
      exception failed to infect cage mates. These are all considered positive
      attributes of a sentinel species for WN virus surveillance programs.

PMID- 11585539
TI  - Widespread West Nile virus activity, eastern United States, 2000.
AB  - In 1999, the U.S. West Nile (WN) virus epidemic was preceded by widespread
      reports of avian deaths. In 2000, ArboNET, a cooperative WN virus surveillance
      system, was implemented to monitor the sentinel epizootic that precedes human
      infection. This report summarizes 2000 surveillance data, documents widespread
      virus activity in 2000, and demonstrates the utility of monitoring virus activity
      in animals to identify human risk for infection.

PMID- 11585540
TI  - Exposure of domestic mammals to West Nile virus during an outbreak of human
      encephalitis, New York City, 1999.
AB  - We evaluated West Nile (WN) virus seroprevalence in healthy horses, dogs, and
      cats in New York City after an outbreak of human WN virus encephalitis in 1999.
      Two (3%) of 73 horses, 10 (5%) of 189 dogs, and none of 12 cats tested positive
      for WN virus-neutralizing antibodies. Domestic mammals should be evaluated as
      sentinels for local WN virus activity and predictors of the infection in humans.

PMID- 11585541
TI  - Detection of North American West Nile virus in animal tissue by a reverse
      transcription-nested polymerase chain reaction assay.
AB  - A traditional single-stage reverse transcription-polymerase chain reaction (RT
      PCR) procedure is effective in determining West Nile (WN) virus in avian tissue
      and infected cell cultures. However, the procedure lacks the sensitivity to
      detect WN virus in equine tissue. We describe an RT-nested PCR (RT-nPCR)
      procedure that identifies the North American strain of WN virus directly in
      equine and avian tissues.

PMID- 11585542
TI  - West Nile virus in overwintering Culex mosquitoes, New York City, 2000.
AB  - After the 1999 West Nile (WN) encephalitis outbreak in New York, 2,300
      overwintering adult mosquitoes were tested for WN virus by cell culture and
      reverse transcriptase-polymerase chain reaction. WN viral RNA and live virus were
      found in pools of Culex mosquitoes. Persistence in overwintering Cx. pipiens may
      be important in the maintenance of WN virus in the northeastern United States.

PMID- 11585543
TI  - West Nile virus outbreak among horses in New York State, 1999 and 2000.
AB  - West Nile (WN) virus was identified in the Western Hemisphere in 1999. Along with
      human encephalitis cases, 20 equine cases of WN virus were detected in 1999 and
      23 equine cases in 2000 in New York. During both years, the equine cases occurred
      after human cases in New York had been identified.

PMID- 11585544
TI  - Isolation and characterization of West Nile virus from the blood of viremic
      patients during the 2000 outbreak in Israel.
AB  - We report the isolation of West Nile (WN) virus from four patient serum samples
      submitted for diagnosis during an outbreak of WN fever in Israel in 2000.
      Sequencing and phylogenetic analysis revealed two lineages, one closely related
      to a 1999 New York isolate and the other to a 1999 Russian isolate.

PMID- 11585545
TI  - Fatal encephalitis and myocarditis in young domestic geese (Anser anser
      domesticus) caused by West Nile virus.
AB  - During 1999 and 2000, a disease outbreak of West Nile (WN) virus occurred in
      humans, horses, and wild and zoological birds in the northeastern USA. In our
      experiments, WN virus infection of young domestic geese (Anser anser domesticus)
      caused depression, weight loss, torticollis, opisthotonus, and death with
      accompanying encephalitis and myocarditis. Based on this experimental study and a
      field outbreak in Israel, WN virus is a disease threat to young goslings and
      viremia levels are potentially sufficient to infect mosquitoes and transmit WN
      virus to other animal species.

PMID- 11585546
TI  - Identification of arboviruses and certain rodent-borne viruses: reevaluation of
      the paradigm.
AB  - Diagnostic and epidemiologic virology laboratories have in large part traded
      conventional techniques of virus detection and identification for more rapid,
      novel, and sensitive molecular methods. By doing so, useful phenotypic
      characteristics are not being determined. We feel that the impact of this shift
      in emphasis has impaired studies of the biology of viruses. This position paper
      is a plea to the scientific and administrative communities to reconsider the
      importance of such information. We also suggest a revised paradigm for virus
      isolation and characterization and provide a rationale for accumulating biologic
      (phenotypic) information.

PMID- 11585548
TI  - Integrated mosquito management: no new thing.

PMID- 11585547
TI  - Treatment of West Nile virus encephalitis with intravenous immunoglobulin.

PMID- 11585550
TI  - Enteric fever treatment failures: a global concern.

PMID- 11585552
TI  - Mycobacterium tuberculosis Beijing genotype, Thailand--reply to Dr. Prodinger.

PMID- 11585553
TI  - Tumor necrosis factor gene polymorphisms in patients with sporadic Parkinson's
      disease.
AB  - We studied promoter region polymorphisms in the tumor necrosis factor (TNF) gene
      at position -1031, -863, and -857, in 172 Japanese patients with sporadic
      Parkinson's disease (PD). The frequency of the -1031C allele, a high producer of
      TNF, increased significantly in early onset PD patients compared with controls.
      In addition, PD patients with the -1031C allele showed a significantly earlier
      onset than those without -1031C allele, after stratification of the data by an
      interleukin-1beta gene polymorphism. Our findings suggest that TNF might have a
      toxic effect in PD.

PMID- 11585555
TI  - Changes of beta-actin mRNA expression in canine vasospastic basilar artery after
      experimental subarachnoid hemorrhage.
AB  - The aim of this study was to investigate whether vascular remodeling occurs
      during cerebral vasospasm after subarachnoid hemorrhage (SAH). Beta-actin mRNA
      expression and structural change of its 3' untranslated region (UTR) which are
      considered a non-specific marker for vascular remodeling, were examined by
      Northern analysis and polymerase chain reaction analysis in a canine basilar
      artery after experimental SAH. The changes in the area of tunica media in the
      basilar artery were also examined histopathologically. Increased beta-actin mRNA
      expression and its structural changes of 3' UTR in the vasospastic basilar artery
      were markedly seen 7 and 14 days after SAH accompanied by increased area of
      tunica media in the basilar artery. The results suggest that vascular remodeling
      occurs and takes part in the luminal narrowing during cerebral vasospasm.

PMID- 11585554
TI  - Dose-related alteration in nitric oxide synthase mRNA expression induced by
      amphetamine and the full D1 dopamine receptor agonist SKF-82958 in mouse
      striatum.
AB  - Neuronal nitric oxide synthase (nNOS) is normally expressed in one population of
      intrinsic interneurons of the striatum. Production of nitric oxide in the nNOS
      containing neurons is sensitive to dopamine stimulation. Using quantitative in
      situ hybridization, the present study investigated the alteration in basal nNOS
      mRNA expression in striatal nNOS-containing neurons of mice treated with the
      psychostimulant amphetamine or a full D1 dopamine receptor agonist, SKF-82958. A
      single systemic injection of amphetamine induced a dose-related change in
      striatal nNOS mRNA expression. Whereas amphetamine at 4 mg/kg decreased basal
      levels of nNOS mRNA in both the dorsal (caudoputamen) and ventral (nucleus
      accumbens) striatum, the drug at a higher dose (12 mg/kg) increased nNOS
      expression in the two regions. Similarly, an acute systemic injection of SKF
      82958 decreased and increased nNOS mRNA levels in the dorsal and ventral striatum
      at 2 and 4 mg/kg, respectively. These data indicate that constitutive nNOS
      expression in nitric oxide-producing neurons of the mouse striatum is regulated
      by dopaminergic transmission. Altered nNOS expression may result in changes in
      nitric oxide synthesis and thus contribute to biological actions of dopamine
      stimulants.

PMID- 11585556
TI  - Changes in brain content of nociceptin/orphanin FQ and endomorphin 2 in a rat
      model of neuropathic pain.
AB  - Orphanin FQ (OFQ) and endomorphins (EM) are newly characterized members of opioid
      peptide family. OFQ has been shown to antagonize morphine analgesia at
      supraspinal level, whereas endomorphins are highly selective endogenous ligands
      for mu receptor, showing analgesic effect at both spinal and supraspinal level.
      OFQ and EM-2 (EM2) immunoreactivity (ir) was measured by radioimmunoassay in
      nociception-related brain areas of rats subjected to L5/L6 spinal nerve ligation,
      using sham operated rats as control. It was found that: (1) the content of EM2-ir
      of spinal nerve ligated rats showed a significant increase (778%) in
      periaqueductal gray (PAG), and a significant decrease (43%) in striatum, compared
      with the control group. (2) a significant increase of the content of OFQ-ir was
      found in amygdala (+841%) and PAG (+459%), respectively in spinal nerve ligated
      rats. High pressure liquid chromatography showed that the EM2-ir and OFQ-ir were
      both heterogeneous with the major part eluting at the position of EM2 and OFQ
      standard, respectively. These results suggest that spinal nerve ligation induces
      significant changes in the content of EM2-ir and OFQ-ir in some discrete brain
      areas, which may play a role in nociceptive modulation.

PMID- 11585557
TI  - Leukemia inhibitory factor induces nociceptin mRNA in cultured rat cortical
      neurons.
AB  - The effects of leukemia inhibitory factor (LIF) on the expression of
      neurotransmitter synthetase and neuropeptide mRNAs in cultured rat cortical
      neurons were examined by reverse transcription-polymerase chain reaction.
      Nociceptin mRNA expression was increased by treatment with 20 or 80 ng/ml LIF for
      24 h, but choline acetyl transferase, glutamic acid decarboxylase, enkephalin,
      dynorphin, substance P, somatostatin and galanin mRNA expression were not altered
      by LIF. These observations indicated a specific effect of LIF on nociceptin gene
      regulation in cultured cortical neurons.

PMID- 11585558
TI  - Genetic interaction between shibire and comatose mutations in Drosophila suggest
      a role for snap-receptor complex assembly and disassembly for maintenance of
      synaptic vesicle cycling.
AB  - NSF is an ATPase required for the fusion of secretory vesicles with plasma
      membrane. Conditional comatose (Drosophila homolog of N-ethylmaleimide sensitive
      fusion factor (NSF)) mutations in Drosophila block synaptic transmission at
      restrictive temperature. Current models hold that NSF-mediated dissociation of
      SNARE (SNAp REceptor) complexes on mature synaptic vesicles primes them for
      exocytic release. Paralysis in comt mutants thus reflects defective exocytosis
      due to buildup of unresolved SNARE complexes. Here, we analyze effects of
      blocking synaptic vesicle recycling on behavioral, physiological and biochemical
      phenotypes of comt. Behavioral recovery of comt animals and recovery of comt
      synapses, as assayed by electroretinograms, after exposure to high temperature is
      faster if synaptic vesicle recycling is simultaneously blocked using shi(ts)
      mutants. Concurrently, 7S complex buildup in comt shi double mutants is
      substantially lower than in comt mutants alone. In addition, we find that 7S
      complexes can form on presynaptic plasma membrane if NSF is inhibited after
      synaptic-vesicle depletion. Thus, our experiments demonstrate a need for
      continuous NSF activity required not only for dissociating cis-SNARE complexes on
      plasma membrane after exocytosis, but also for maintaining these cis-SNARE
      complexes in a dissociated state.

PMID- 11585559
TI  - Long-lasting memory of sounds combined with reward in rats.
AB  - We investigated the effects of sound stimuli combined with reward on the
      subsequent sound discrimination. Water-deprived rats were exposed to one of two
      sounds (S+ or S-) in a trial, and licking a spout only during the presentation of
      S+ was rewarded with water. The percentage of trials in which licking occurred
      was calculated separately for S+ and S-, and sound discrimination was estimated
      from the difference in the percentage. S+ and S- were significantly discriminated
      during an 8 h period. In the second test after 1-2 weeks, sound discrimination
      for the same S+ and S- was significantly better than that for the S+ of the
      previous S- and S- of the previous S+. These findings indicate that the memory of
      the sounds combined with reward in the first test was maintained for 1-2 weeks.

PMID- 11585560
TI  - EEG gamma-band phase synchronization between posterior and frontal cortex during
      mental rotation in humans.
AB  - The main purpose of the present paper was: (1) to study the phase synchronization
      pattern in the gamma-band while performing the classical Shepard-Metzler task of
      mental rotation; (2) to investigate the role of musical training; and (3) to
      study hemispheric differences in the degree of synchronization during mental
      rotation. Multivariate electroencephalograph signals from 20 male subjects (ten
      musicians and ten non-musicians) were recorded while performing the mental
      rotation task and also at resting condition. Phase synchronization was measured
      by a recent index, mean phase coherence. It was found that synchronization
      between frontal cortex and right parietal cortex was significantly increased
      during mental rotation with respect to rest, whereby musicians showed
      significantly higher degrees of synchronization than non-musicians. Left
      hemispheric dominance in the degree of phase synchronization, stronger in the
      posterior right parietal and occipital regions, was observed in musicians. Right
      hemispheric dominance was generally observed in non-musicians.

PMID- 11585561
TI  - Directional responses of basal optic neurons are modulated by the nucleus
      lentiformis mesencephali in pigeons.
AB  - The nucleus lentiformis mesencephali (nLM) and the nucleus of the basal optic
      root (nBOR) in pigeons are both involved in optokinetic nystagmus. They are
      reciprocally connected and thus may interact with each other. The present study
      injected lidocaine into nLM and then examined the effects of nLM blockade on
      visual responses of nBOR neurons to target motion. The results indicate that nLM
      could modulate nBOR activity in two ways. First, nLM enhances visual responses of
      70% of nBOR cells to motion in the preferred directions, sharpening their
      directional tuning. Second, nLM reduces visual responses of 13% of nBOR cells to
      motion in the preferred directions, broadening their directional tuning. The
      remaining 17% of nBOR cells are not affected by drug application. Taken together
      with the previous results that nBOR could modulate nLM activity (Gu et al.,
      Neuroscience, 104 (2001) 153), it suggests that both nuclei can mutually modulate
      each other in generating optokinetic nystagmus.

PMID- 11585562
TI  - Human pre-attentive auditory change-detection with single, double, and triple
      deviations as revealed by mismatch negativity additivity.
AB  - The functional nature of the pre-attentive automatic auditory feature analysis
      was investigated using the mismatch negativity (MMN) component of the auditory
      event-related brain potential. MMNs to ignored sounds deviating in one, two or
      three dimensions (duration (D), frequency (F), intensity (I)) were recorded. When
      the corresponding MMN processes elicited by stimuli simultaneously deviating in
      multiple features are independent from each other, then the empirically measured
      MMN elicited by multiple deviants equals the sum of the MMINs elicited by the
      corresponding single deviants. Indeed, MMNs to double DF- and to double DI
      deviants showed additivity for frontocentral as well as for subtemporal sites,
      whereas MMN to double FI-deviants and MMN to triple DFI-deviants were additive
      only at subtemporal sites indicating that frontal and temporal MMN generators
      reveal differential degree of additivity. This finding demonstrates that not all
      combinations of stimulus dimensions are processed independently from each other.

PMID- 11585563
TI  - Roles of central interleukin-1 on stress-induced-hypertension and footshock
      induced-analgesia in rats.
AB  - Central interleukin-1 (IL-1) plays an important role in mediating the neural,
      endocrine, and behavioral responses to stressors. Here we tested whether central
      IL-1 is involved in stress-induced hypertension or footshock (FS)-induced
      analgesia. We observed that: (1) intracerebral ventricular injection of (ICV) IL
      1beta induced pressor responses; (2) hypertension induced by IL-1beta was blocked
      by ICV an IL-1 antagonist, IL-1ra; (3) ICV IL-1ra attenuated the pressor response
      induced by FS but intravenous injection of IL-1ra did not significantly reduce
      this response; (4) the hypertensive response to conditioned fear stimuli was
      reversed by ICV IL-1ra; (5) FS-induced-analgesia was attenuated by ICV IL-1ra and
      this effect disappeared 15 min after ICV IL-1ra. These results suggest that both
      the pressor response to FS or conditioned fear stimuli and short lasting
      analgesia induced by FS are mediated by central IL-1.

PMID- 11585564
TI  - Hypermetabolism of paraventricular hypothalamus in the congenitally helpless rat.
AB  - The congenitally helpless rat, selectively bred to model behavioral features of
      depression, has shown metabolic activity patterns in frontal and cingulate cortex
      similar to those detected in human imaging studies of depression and sadness.
      This study extends the same metabolic mapping technique (quantitative cytochrome
      oxidase histochemistry) to the hypothalamus, where activity levels were assessed
      in six nuclei: paraventricular nucleus, medial preoptic area, lateral
      hypothalamic area, supraoptic nucleus, suprachiasmatic nucleus, and ventromedial
      nucleus. Helpless rats were compared with a strain of non-helpless rats
      selectively bred for stress resistance. Only the paraventricular nucleus showed a
      significant group difference, with helpless rats showing elevated metabolism and
      non-helpless rats showing reduced metabolism relative to normal rats. Thus,
      paraventricular nucleus activity may be associated with genetic susceptibility to
      helpless behavior.

PMID- 11585565
TI  - Inflammation with no axonal damage of the rat saphenous nerve trunk induces
      ectopic discharge and mechanosensitivity in myelinated axons.
AB  - Inflammation along a nerve trunk with no frank axonal nerve damage produced by
      complete Freund's adjuvant (CFA) or Carrageenan is known to induce a painful
      peripheral neuropathy. In the present study, we examined the electrophysiological
      properties of myelinated axons (spontaneous discharge and mechanical sensitivity)
      at the inflamed nerve site. The rat saphenous nerves were exposed at mid-thigh
      level and wrapped in 2 mm wide bands of haemostatic oxidized cellulose (Oxycel)
      that were saturated with undiluted CFA. In the control rats the Oxycel) was
      saturated with saline. At postoperative days (PODs) 2-5 and 6-10, fine axon
      bundles were teased from the nerve, and electrophysiological recordings
      performed. At both time points spontaneous activity at the site of the
      application in CFA rats (PODs 2-5=9.9+/-2.5%: PODs 6-10=6.1+/-1.4%) was
      significantly higher than in the control animals (PODs 2-5=2.9+/-1.1%: PODs 6
      10=1.6+/-1.4%: P=0.03, P=0.02, respectively). Mechanical sensitivity at both time
      points was significantly higher in CFA rats (PODs 2-5=12.6+/-3.1%: PODs 6
      10=10.3+/-3.1%) than in saline rats (PODs 2-5=3.4+/-2.91%: PODs 6-10=0.8+/-1.0%:
      P=0.03, P=0.04, respectively). This study clearly shows that perineural
      inflammation with no axonal nerve damage induced by CFA application around the
      nerve trunk elevates spontaneous activity and induces mechanosensitivity in
      myelinated axons.

PMID- 11585566
TI  - Manganese mimics the action of 1-methyl-4-phenylpyridinium ion, a dopaminergic
      neurotoxin, in rat striatal tissue slices.
AB  - Manganese and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are known to
      induce neurological pathologies similar to that of parkinsonism. Previous studies
      performed in rat striatal slices have shown that MPTP and related compounds
      inhibit tyrosine hydroxylation, a rate-limiting step of dopamine biosynthesis.
      Here, we reported that manganese inhibited tyrosine hydroxylation in rat striatal
      slices. In addition, manganese caused increase in the levels of lactate
      indicating that aerobic glycolysis was inhibited in striatal slices. This
      inhibition was unique to manganese since other divalent cations, such as
      magnesium and zinc, did not increase lactate concentrations. These results
      suggest that the mechanisms by which manganese produces dysfunction of the
      nervous system are similar to those of MPTP.

PMID- 11585567
TI  - Neurons in the lateral paragigantocellular nucleus projecting to the infralimbic
      cortex in rats: electrical activity and response to changes in blood pressure.
AB  - Neurons in the lateral paragigantocellular nucleus (LPGi) are known to project
      directly to the infralimbic cortex (IL). However, there have been no
      physiological studies on LPGi neurons projecting to the IL. In urethane
      anesthetized rats, the single-unit activities of LPGi neurons were recorded
      extracellularly to investigate their electrophysiological properties and
      responses to changes in blood pressure (BP). The LPGi neurons antidromically
      driven from the IL were restricted to the ventral part of the LPGi and most
      spontaneously active neurons revealed suppression of activity following a fall in
      BP. These results suggest that the LPGi neurons in a very restricted location
      influence the IL in response to changes in BP.

PMID- 11585568
TI  - cAMP is involved in the differentiation of human teratocarcinoma cells.
AB  - The generation of fully differentiated post-mitotic human neuronal cells from
      stem cells (human teratocarcinoma (hNT2) cells) might enable the development of a
      co-culture model of human neurons with human Schwann cells (SCs). This co-culture
      model is an important tool to study formation of myelin sheaths. However, the
      thin process of the post-mitotic human neuronal cells formed under known culture
      conditions do not provide a good substrate for human SCs to start myelination. We
      optimized the culture conditions of these cells to obtain axons with a larger
      diameter. Western blotting and immunofluorescence studies were performed to
      confirm the neuronal status of the cells and diameter of the processes. In this
      study, we show that addition of cAMP-inducing factors to hNT2 cells resulted in
      rapid morphological changes including the development of processes with a larger
      diameter.

PMID- 11585569
TI  - Prolonged survival of axons terminating within lesions of cat visual cortex.
AB  - It is well known that brain lesions made by the injection of ibotenic acid
      destroy neuronal cell bodies but do not kill passing axons. We have found that
      axons terminating within such lesions in visual cortex also survive for at least
      2 months, despite the absence of available synaptic sites. We made tracer
      injections in area 17, and observed dense patches of anterograde label within
      lesions in other visual cortical areas. Furthermore, because the retinotopic site
      of the tracer injection was known, we could conclude that the retinotopic site
      was encompassed within the lesion.

PMID- 11585570
TI  - Calcitonin gene-related peptide-mediated increase in K(+)-induced [(3)H]-dopamine
      release from rat caudal striatal slices.
AB  - The calcitonin-gene receptor peptide (alphaCGRP) receptor is present in high
      levels in the caudal striatum of the rat. Previous behavioural experiments have
      highlighted a possible correlation between alphaCGRP-mediated effects and the
      dopaminergic system. In this study, we examined the effect of alphaCGRP on K(+)
      evoked [(3)H]-dopamine release in a slice preparation of the rat caudal striatum.
      The unstimulated release of [(3)H]-dopamine was not affected by alphaCGRP.
      However, alphaCGRP increased the release of [(3)H]-dopamine evoked by K(+) (30
      mM) in a concentration-dependent manner. The stimulatory effect of alphaCGRP was
      blocked by the CGRP1 antagonist hCGRP(8-37) (without effect on its own). The
      stimulatory effect of 1 microM alphaCGRP was blocked by dizocilpine (MK-801),
      suggesting that excitatory transmission is involved in mediating the facilitated
      release. This study suggests that the peptide alphaCGRP, modulates dopamine
      release in the rat caudal striatum probably indirectly via glutamatergic
      transmission.

PMID- 11585571
TI  - Brain alpha-endosulfine is manifold decreased in brains from patients with
      Alzheimer's disease: a tentative marker and drug target?
AB  - Alpha-endosulfine has the sulfonylurea-like ability to block ATP-sensitive
      potassium (K(ATP)) channels, which can stimulate insulin secretion in beta cell.
      Although the blockade of K(ATP) channels has been reported to be involved in
      neurotransmitter release, the neurobiological role of alpha-endosulfine has not
      been studied yet. We examined the protein levels of alpha-endosulfine in frontal
      cortex and cerebellum from patients with Alzheimer's disease (AD). Alpha
      endosulfine was extremely decreased in both regions of AD compared to controls.
      This could result in the continuous opening of K(ATP) channels with subsequent
      decrease of neurotransmitter release and change of potassium fluxes. This study
      is of great significance for providing a neurobiological function of brain alpha
      endosulfine and furthermore, alpha-endosulfine could serve as a useful marker for
      the diagnosis of AD and a target for drug treatment.

PMID- 11585572
TI  - Effect of zenarestat, an aldose reductase inhibitor, on endoneurial blood flow in
      experimental diabetic neuropathy of rat.
AB  - The effects of zenarestat, an aldose reductase inhibitor, on endoneurial blood
      flow (NBF) were explored in streptozotocin-induced diabetic rats. Rats were
      maintained on a diet of containing 0.09% zenarestat for 8 weeks, then NBF in the
      sciatic nerve was measured using microelectrode hydrogen polarography. NBF in the
      diabetic control rats was significantly lower than values in age-matched control
      rats, however, NBF was not significantly altered in diabetic rats treated with
      zenarestat. Direct application of nitric oxide synthase inhibitor, NG-nitro-L
      arginine, did not affect NBF in diabetic control rats, whereas this application
      significantly reduced NBF both in age-matched control and zenarestat treated
      diabetic rats. Considerable levels of zenarestat were confirmed in the sciatic
      nerve in the drug treated rats. These data suggest that aldose reductase, such as
      zenarestat, might restore or prevent the alteration of endoneurial blood flow
      resulting from an impairment of nitric oxide function.

PMID- 11585573
TI  - Glutamate transport in rat cerebellar granule cells is impaired by inorganic
      epileptogenic agents.
AB  - There is evidence that extracellular glutamate levels are elevated in certain
      brain regions immediately prior to and during induction and propagation of
      seizures. There appears to be a correlation between the capacity of removing
      released glutamate and the genesis of epileptiform activity. Some models make use
      of metals, such as Co(2+) and Ni(2+), to induce epilepsy. We used patch-clamp
      recordings to measure the electrogenic glutamate transport in neuronal cells. The
      present results indicate that Co(2+) (1 mM) and Ni(2+) (5 mM) blocked glutamate
      transport by 17.6+/-3.9% (n=5, P<0.05) and by 31.8+/-6.2% (n=7, P<0.05),
      respectively. Ni(2+) inhibited glutamate uptake in a dose-dependent manner. The
      IC(50) value obtained was 66.6 microM and the maximum inhibition was 40%. We
      conclude that one mechanism that may explain the seizures induced by exposure to
      those divalent cations is inhibition of the glutamate transporter.

PMID- 11585574
TI  - Nitric oxide inhibits the proliferation of murine microglial MG5 cells by a
      mechanism involving p21 but independent of p53 and cyclic guanosine
      monophosphate.
AB  - We investigated the effect of nitric oxide (NO) on the proliferation of
      microglial MG5 cells established from p53-deficient mice. Cells were treated with
      bacterial lipopolysaccharide and interferon-gamma, and expression of inducible NO
      synthase (iNOS) and p21/waf1, a cyclin-dependent kinase inhibitor protein which
      is a critical downstream effector of p53, was investigated by RNA blot and
      immunoblot analyses. iNOS mRNA was induced 2 h after treatment and increased with
      time up to 24 h. p21 mRNA was expressed at a low level in untreated cells and
      increased with a kinetics similar to that for iNOS mRNA. iNOS and p21 proteins
      were also induced. An NO donor SNAP induced p21 mRNA and protein. SNAP inhibited
      incorporation of [(3)H]thymidine in MG5 cells in a dose-dependent manner. 8-Bromo
      cGMP neither induced p21 mRNA nor inhibited [(3)H]thymidine incorporation. These
      results suggest that NO inhibits the proliferation of MG5 cells by induction of
      p21, which occurs independent of p53 and cGMP.

PMID- 11585575
TI  - Event-related potentials in an auditory semantic oddball task in humans.
AB  - Whenever rare target stimuli are presented interspersed by frequent irrelevant
      stimuli (standards), the targets elicit a late parieto-central positive wave
      called P3. Usually standards and targets differ by a simple physical feature
      (e.g. tone pitch). Less consistent are the data obtained in semantic tasks, in
      which standards and targets are represented by different word classes. Given an
      equal number of words in the target and standard categories, each individual
      standard is more frequent than each target, that is, the frequency of the
      category is confounded with that of individual stimuli. In the present study
      participants were presented five semantic classes each being represented by 15
      words. Words belonging to one particular class should be counted. Thus targets
      were rare (20%), although the frequencies of each word and of each semantic class
      were equal. A highly significant P3 was recorded. Its latency was longer, and the
      amplitude was smaller, than when standards and targets were two tones. These data
      indicate that brain waves recorded in semantic tasks are not necessarily
      manifestations of specific semantic processing.

PMID- 11585576
TI  - Intracerebroventricular injection of pipecolic acid inhibits food intake and
      induces sleeping-like behaviors in the neonatal chick.
AB  - It has been demonstrated that L-pipecolic acid (L-PA), a major metabolic
      intermediate of L-Lysine (L-Lys) in the brain, is involved in the functioning of
      Gamma-aminobutyric acid. In the present work the effect of
      intracerebroventricular (i.c.v.) administration of L-PA, and its relatives, on
      food intake and behavior in neonatal chicks was investigated. The i.c.v.
      injection of 1 mg of L-PA and D-PA significantly inhibited food intake during the
      2 h following injection, whereas greater than 2 mg of L-Lys was required to
      inhibit food intake. In behavioral tests, the i.c.v. injection of L-PA reduced
      active wakefulness and feeding behavior while inducing sleeping-like behavior in
      chicks. These results suggest that L-PA has an important role for the regulation
      of behaviors in the neonatal chick after conversion from L-Lys in the brain.

PMID- 11585577
TI  - Correlation between local glucose transporter densities and local 3-O
      methylglucose transport in rat brain.
AB  - The present study addresses the question whether local glucose transport kinetics
      are correlated with local glucose transporter densities in the brain. In 47 brain
      structures the local rate constants for 3-O-[(14)C]methylglucose (3-O-MG)
      transport, K(1) and k(2,) were quantified, and local glucose Glut1 and Glut3
      transporter densities were determined by immuno-autoradiographic methods.
      Statistically significant correlations were found between the rate constants for
      glucose transport and the transporter densities. The correlations were tighter
      for Glut1 than for Glut3. Inasmuch as 3-O-MG is transported by the same
      transporter as glucose, these results indicate that the local densities of
      glucose transporters determine local glucose transport rates in the brain.

PMID- 11585578
TI  - Magnetic stimulation induces neuronal c-fos via tetrodotoxin-sensitive sodium
      channels in organotypic cortex brain slices of the rat.
AB  - Repetitive transcranial magnetic stimulation is a novel non-invasive method with
      antidepressant properties, where electromagnetic fields are applied via an
      electrode. The aim of the present study was to investigate in an in vitro model
      if magnetic stimulation may activate the transcription factor c-fos. Organotypic
      brain slices of the parietal cortex were cultured for 2 weeks and then treated
      with a magnetic stimulator. Immunohistochemistry was used to detect c-fos like
      immunoreactivity. We show that magnetic stimulation (1 Hz, 10 min, 75% machine
      output/magstim 200 rapid stimulator) transiently enhanced c-fos 3-6 h after
      stimulation. Co-localization experiments revealed that c-fos was expressed in
      neurons but not astroglia. The activation of c-fos by magnetic stimulation was
      inhibited by the sodium-channel blocker tetrodotoxin (TTX) (10 microM). It is
      concluded that magnetic stimulation induces neuronal c-fos via TTX-sensitive
      sodium channels in organotypic cortex slices.

PMID- 11585579
TI  - Colocalization of neuronal nitric oxide synthase and neurokinin-1 receptor in
      striatal interneurons in the rat.
AB  - It has been established that nitric oxide synthase (NOS)-containing aspiny
      neurons constitute one class of interneurons in the striatum, and that substance
      P (SP)-containing projection neurons give off many axon collaterals within the
      striatum. In the present study, we investigated a morphological substrate of
      possible influences of SP-containing projection neurons upon NOS-containing
      interneuron in the rat striatum; colocalization of immunoreactivities for NOS and
      NK-1 type tachykinin receptor (NK1R: SP receptor) was examined by a double
      immunofluorescence histochemistry. The vast majority (94.6%) of NOS-positive
      neurons showed NK1R immunoreactivity, whereas only smaller cells of NK1R-positive
      neurons (61.2% of NK1R-positive neurons) displayed NOS immunoreactivity. The
      results indicated that the NOS-containing interneurons were under direct control
      of SP-containing projection neurons in the striatum.

PMID- 11585580
TI  - Combined epineurial therapy with neutralizing antibodies to tumor necrosis factor
      alpha and interleukin-1 receptor has an additive effect in reducing neuropathic
      pain in mice.
AB  - Monotherapy with antibodies to tumor necrosis factor-alpha (TNF) or interleukin-1
      receptor 1 (IL-1R1) reduces hyperalgesia in an animal model of painful
      neuropathy. Here we investigated whether combined therapy with epineurial anti
      TNF and anti-IL-1R1 antibodies produces a further advantage. C57BL/6 mice with a
      chronic constrictive injury of one sciatic nerve were treated epineurially with
      neutralizing antibodies to either IL-1R1 or TNF alone or with a combined
      application of neutralizing antibodies to TNF and IL-1R1. Combined treatment with
      anti-IL-1R1 and anti-TNF antibodies markedly reduced thermal hyperalgesia and
      mechanical allodynia more effectively than monotherapy with either antibody.
      There were no detectable differences in IL-1beta and TNF endoneurial protein
      expression between animals with monotherapy and combined treatment. We conclude
      that combined anti-cytokine therapy may be a useful strategy in the treatment of
      neuropathic pain.

PMID- 11585581
TI  - Riluzole stimulates nerve growth factor, brain-derived neurotrophic factor and
      glial cell line-derived neurotrophic factor synthesis in cultured mouse
      astrocytes.
AB  - Riluzole is an antiexcitotoxic agent used for the treatment of amyotrophic
      lateral sclerosis, and reported to have neuroprotective effects in animal models
      of Parkinson's disease, Huntington's disease and brain ischemia. We investigated
      the effects of riluzole on synthesis of nerve growth factor (NGF), brain-derived
      neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF)
      in cultured mouse astrocytes. The protein and mRNA levels were measured by enzyme
      linked immunosorbent assay and semiquantitative reverse transcription-polymerase
      chain reaction, respectively. Treatment with riluzole at 100 microg/ml (426
      microM) for 24 h increased the contents of NGF, BDNF, and GDNF in the culture
      medium 109-fold, 2.0-fold and 3.1-fold over the control, respectively. The drug
      induced relative mRNA levels of NGF, BDNF, and GDNF were 7.3-fold at 2 h, 2.1
      fold at 4 h, and 1.9-fold at 2 h, respectively. These results indicate that
      riluzole stimulates synthesis of NGF, BDNF and GDNF in cultured astrocytes.
      Riluzole might exert neuroprotective effects, at least in part, via stimulation
      of neurotrophic factors.

PMID- 11585582
TI  - The nNOS/cGMP signal transducing system is involved in the cardiovascular
      responses induced by activation of NMDA receptors in the rostral ventrolateral
      medulla of cats.
AB  - Nitric oxide (NO) is synthesized from L-arginine by NO synthase (NOS). NO
      stimulates the soluble form of guanylyl cyclase (sGC) and induces accumulation of
      cyclic guanosine monophosphate (cGMP). The purpose of this study was to examine
      whether the cardiovascular responses induced by N-methyl-D-aspartate (NMDA) in
      the rostral ventrolateral medulla (RVLM) depend on the actions of NOS and sGC. In
      anesthetized cats, the extracellular NO level was measured by in vivo voltammetry
      using a nafion/porphyrine/o-phenylenediamine-coated carbon-fiber electrode.
      Microinjection of NMDA into the RVLM produced hypertension and bradycardia
      associated with NO formation. These NMDA-induced responses were attenuated by
      prior injections of 7-nitroindazole, a neuronal NO synthase (nNOS) inhibitor, and
      1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a sGC inhibitor. These findings
      suggest that NO is involved in the NMDA-induced cardiovascular responses in the
      RVLM.

PMID- 11585583
TI  - Transient expression of phospholipase D1 in developing rat hippocampus.
AB  - We investigated the distribution of phospholipase D1 (PLD1) protein in the
      developing rat hippocampus using an affinity-purified peptide antibody against
      PLD1. Immunoreactivity for PLD1 was first seen in some scattered cells in the
      hippocampus at embryonic day 18. At postnatal day 1 (P1), many PLD1
      immunoreactive cells were observed in the CA1 and CA3 sectors, subiculum and the
      hilus of the dentate gyrus. During the first postnatal week, there was an abrupt
      increase of immunoreactive neurons in the hippocampus, and their number and
      intensity peaked at P7. During the second postnatal week, there was an abrupt
      decrease in the number of immunoreactive hippocampal neurons. By P14, no
      significant labeling was found in the hippocampus. These results corresponded
      well with those from Western blot analysis, suggesting that PLD1 may regulate the
      developmental processes of hippocampal neurons.

PMID- 11585584
TI  - Response of renal sympathetic nerve activity to parabolic flight-induced
      gravitational change in conscious rats.
AB  - The renal sympathetic nerve activity (RNA) response to gravitational changes
      induced by parabolic flight was examined in chronically instrumented conscious
      rats. Two types of RNA responses were found. In six out of 12 rats, the RNA did
      not respond during the 2 G period, but immediately fell to background levels on
      entry into microgravity (microG), then recovered to the 1 G control level during
      continued microG (shutdown obvious group). In the other six rats, the RNA
      increased to 158+/-13% at the end of the 2 G period, increased further to 195+/
      22% on entry into microG, then gradually recovered to that seen at 1 G (shutdown
      obscure group). The mean arterial pressure in the shutdown obvious group was
      significantly higher and the heart rate tended to be higher than in the shutdown
      obscure group, suggesting that the baseline sympathetic tone in the shutdown
      obvious group was higher than in the shutdown obscure group. These results
      suggest that the RNA response to parabolic flight might be affected by the
      baseline sympathetic tone.

PMID- 11585585
TI  - Long-term memory traces facilitate short-term memory trace formation in audition
      in humans.
AB  - Long-term memory traces of one's native language have an effect on the short-term
      memory traces formed by phonemes, Nature 385 (1997) 432. We investigated whether
      they also affect the number of stimulus repetitions needed to form an adequate
      memory trace used in the elicitation of the mismatch negativity (MMN), an event
      related response to a change in an ongoing sound stream. We recorded MMNs to
      infrequent stimuli occurring in trains of prototype and non-prototype phonemes,
      matched in their physical distances, and in trains of sinusoidal tones. We found
      that the number of standards needed to produce a prominent MMN was smaller for
      native-language prototype phonemes than to non-prototype phonemes, suggesting a
      faster trace development.

PMID- 11585586
TI  - The role of theta and alpha oscillations for language comprehension in the human
      electroencephalogram.
AB  - The hypothesis is tested, whether increasing language processing demands draw on
      the capacity of working memory thereby leading to an increase in theta band
      power. Previous research has shown that theta reflects working memory whereas
      upper alpha semantic memory demands. Sentences were presented in four chunks in a
      reading and a semantic task. In the latter, subjects had to find a superordinate
      concept to a noun presented in the third chunk. The data show an increase in
      theta during sentence processing which was significantly smaller in the semantic
      task. In contrast, the upper alpha band exhibited a significantly larger change
      in band power during the semantic task and that time window in which subjects
      searched for the superordinate concept. Thus, we conclude that semantic
      processing does not draw selectively on the capacity of working memory and that
      different linguistic processes have no direct influence on theta oscillations.

PMID- 11585587
TI  - Hypothalamic 11,12-epoxyeicosatrienoic acid attenuates fever induced by central
      interleukin-1beta in the rat.
AB  - Inhibitors of cytochrome P-450 augment fever in rats and mice, indicating that
      the metabolite of the enzyme is candidate of endogenous antipyretic. Cytochrome P
      450 of arachidonic acid cascade leads to the formation of regioisomeric 5,6-, 8,9
      11,12- and 14,15-epoxyeicosatrienoic acid (EET). Various isomers of EET were
      administrated into the preoptic area and anterior hypothalamus (PO/AH) to test
      their influence on fever induced by interleukin-1beta (IL-1beta) administrated
      into the PO/AH in conscious rats. The IL-beta-induced fever was attenuated in the
      11,12-EET-pretreated rats, although 5,6-, 8,9- and 14,15-EET did not affect the
      fever. Intra-PO/AH injection of 11,12-EET did not alter normal body temperature.
      The results suggest that 11,12-EET acts in the hypothalamus as an endogenous
      antipyretic.

PMID- 11585588
TI  - Auditory evoked responses upon awakening from sleep in human subjects.
AB  - The hypothesis that a state of hypoarousal upon awakening should lead to a
      decrease in amplitude and an increase in latency of the N1-P2 components of the
      Auditory Evoked Potentials (AEPs) as compared to presleep wakefulness levels, was
      evaluated after two nocturnal awakenings and after the final morning awakening
      from a 7.5-h night of sleep. The amplitude of the N1-P2 complex was reduced upon
      awakening as compared to presleep wakefulness levels, but only following the
      first nocturnal awakening, scheduled after the first 2 h of sleep. This result is
      interpreted as indicating a link between slow wave sleep amount, mainly present
      during the first part of the night, and lowered levels of brain activation upon
      awakening. The reaction times, recorded concomitantly to AEPs, were more
      sensitive to the negative effects of sleep inertia.

PMID- 11585589
TI  - Denervation causes changes in electrophysiological properties in rat phrenic
      motoneurons.
AB  - Thirty-nine male adult rats were divided into a control group and a denervation
      group that had been subjected to phrenicotomy 4 weeks earlier.
      Electrophysiological membrane properties (input resistance and rheobase) of
      phrenic motoneurons were measured from intracellular recordings made with glass
      microelectrodes. Under anesthetized and artificially ventilated conditions, the
      recorded motoneurons were divided into recruited (spike discharge) and non
      recruited (depolarization only) types. There was a significant inverse
      relationship between the rheobase and input resistance in the control rats, but
      not in the denervated rats. In the control rats, the mean value of rheobase in
      the non-recruited motoneurons was significantly higher than that in the recruited
      motoneurons. In denervated rats, however, the mean value of rheobase in the
      recruited motoneurons was identical to that in the non-recruited motoneurons. The
      results indicated that phrenicotomy induced a de-differentiation of
      electrophysiological properties of the phrenic motoneurons, and that these
      changes might be restricted to the motoneurons innervating fast-twitch, low
      fatigue resistance muscle fibers.

PMID- 11585590
TI  - Decreased susceptibility to pentylenetetrazol-induced seizures after low
      frequency transcranial magnetic stimulation in rats.
AB  - We studied the effects of low-frequency repetitive transcranial magnetic
      stimulation (rTMS) on seizure susceptibility in rats. rTMS of 1000 pulses at 0.5
      Hz led to a prolonged latency for seizure development after an intraperitoneal
      injection of pentylenetetrazol. The rTMS effectively prevented the development of
      status epilepticus of pentylenetetrazol-induced convulsions. These findings
      indicate that low-frequency rTMS affects the neural excitability, in the
      direction of anticonvulsive, and therefore, suggest the possibility of
      therapeutic use of rTMS in epilepsy.

PMID- 11585591
TI  - Identification of tyrosine hydroxylase gene expression in rat spleen.
AB  - This study was aimed to identify tyrosine hydroxylase (TH) gene expression in the
      rat spleen under basal and stress conditions. Using the reverse transcription
      polymerase chain reaction we did not detect TH mRNA in rat spleen either in
      control, or immobilized animals. Semi-nested PCR revealed a clear signal,
      demonstrating that TH mRNA is formed in the spleen, although in low abundance. We
      also detected both, TH immunoreactive protein and TH activity in the rat spleen
      that were in higher abundance than expected from the mRNA levels. This study
      identifies, for the first time, TH gene expression in rat spleen. Since TH
      protein and activity are present in the spleen in much higher abundance compared
      to corresponding mRNA, the majority of TH protein is most probably supplied by
      the sympathetic innervation of spleen.

PMID- 11585592
TI  - Intracellular chloride concentration is higher in rod bipolar cells than in cone
      bipolar cells of the mouse retina.
AB  - Bipolar cells (BCs) have antagonistic center-surround receptive field. Surround
      illumination evokes depolarization in the OFF-type cone BC, and hyperpolarization
      in the rod BC and the ON-type cone BC. Surround illumination reduces gamma
      aminobutyric acid (GABA) release from horizontal cells. If GABA hyperpolarize
      BCs, the polarity of the GABA-induced effect agrees with the light-evoked
      surround response in the OFF-type BC, but contradicts in the rod BC and the ON
      type cone BC. Immunohistochemical study of the Cl(-) transporter of BCs has
      suggested that the intracellular Cl(-) concentration is different among BC
      subtypes. We examined the reversal potential of GABA-induced current of BCs using
      gramicidin-perforated patch clamp technique in the mouse retina, and found that
      GABA depolarizes rod BC and hyperpolarizes cone BCs. Our results are consistent
      with the GABAergic input to rod BC dendrite.

PMID- 11585593
TI  - Relative contribution of ankle and hip muscles in regulation of the human
      orthograde posture in a frontal plane.
AB  - It was investigated, whether the postural regulation in the frontal plane takes
      place mainly at the hip or at the ankle level. The elimination of ankle torque
      was achieved by providing a point support in the frontal plane. (Two boards were
      attached to subject feet, below each board a metal pipe 2 cm diameter was fixed,
      so, the subject stood on contrivances resembling 'skates'). The lateral
      displacements of breast and hip, the angle of 'skates' tilt and the
      characteristics of frontal stabilogram and electromyogram of two ankle muscles
      (m. peroneus and m. soleus) were compared in two situations: (1) during normal
      standing; (2) under the conditions of the exclusion of ankle torque from postural
      control. During normal standing the body behaved as two-link inverted pendulum.
      Transition from normal standing to standing on free 'skates' produced changes in
      the kinematics of body movement. Under the conditions of ankle torque exclusion
      (free 'skates') breast and hip of a subject moved in a frontal plane as a single
      unit (one-link inverted pendulum). During standing on free 'skates' the
      electromyographic activity of m. peroneus and m. soleus was the same as during
      normal standing (approximately 70-100 microV).

PMID- 11585594
TI  - The calcitonin gene-related peptide (CGRP) antagonist CGRP(8-37) blocks
      vasodilatation in inflamed rat skin: involvement of adrenomedullin in addition to
      CGRP.
AB  - The neuropeptide calcitonin gene-related peptide (CGRP) is a potent microvascular
      vasodilator in rat skin and effects are antagonised by CGRP(8-37). In this study,
      CGRP(8-37) significantly (P<0.05) inhibited the time-dependent (3-5 h) increase
      in skin blood flow measured in the anaesthetised rat, after intradermal
      administration of the inflammatory cytokine interleukin-1beta (3 pmol/site),
      indicating the involvement of CGRP1 receptors. The CGRP-related peptide
      adrenomedullin (ADM) is also a potent vasodilator in rat skin, with effects
      antagonised by CGRP(8-37). We show that ADM mRNA expression is increased in rat
      skin after treatment with IL-1beta and that the IL-1beta-induced blood flow is
      blocked by a selective ADM antibody (P<0.05). Thus ADM is expressed locally in
      the inflamed cutaneous microvasculature where it can, in addition to, or as an
      alternative to CGRP, contribute to IL-1beta-induced vasoactive effects.

PMID- 11585595
TI  - Cell cycle induction in post-mitotic neurons proceeds in concert with the initial
      phase of programmed cell death in rat.
AB  - Neuronal programmed cell death (PCD) is increasingly becoming recognized as a
      dynamic process that may be amenable to resolution. Critical to this resolution
      is the identification of the cellular pathways that modulate the initial stages
      of apoptotic death. In this regard, we examined whether the activation of a
      latent cell cycle was associated with the initial phase of PCD. We demonstrate
      that free radical nitric oxide induced PCD results in the rapid generation of
      membrane phosphatidylserine residue exposure. This early phase of PCD functions
      in parallel with an untoward attempt to enter the cell cycle in the same
      population of post-mitotic neurons. We therefore offer an attractive molecular
      target to prevent or reverse neuronal PCD by elucidating a novel mechanism
      through which the majority of neurons meet their demise by attempting to enter a
      latent cell cycle.

PMID- 11585596
TI  - Rhythmic variation in gamma-aminobutyric acid(A)-receptor subunit composition in
      the circadian system and median eminence of Syrian hamsters.
AB  - Temporal changes in the level of expression of gamma-aminobutyric acid (GABA)(A)
      receptor subunits alpha2, alpha5, beta1 and beta3 were characterized by Western
      blot analysis in the hamster suprachiasmatic nuclei, retina and median eminence.
      A nocturnal maximum in the level of GABA(A) receptor beta1 subunit at midday and
      midnight (12:00 and 00.00 h) was found in the suprachiasmatic nucleus (SCN), the
      retina and the median eminence of Syrian hamsters. Alpha2 and beta3 subunit
      levels peaked during the day in the median eminence. Finally, retinal alpha5
      levels were maximal during the night. beta1 temporal changes in the SCN and
      median eminence, as well as alpha2 variations in the median eminence were
      maintained under constant dark conditions, suggesting an endogenous control,
      while the other variations were only observed under light-dark cycle conditions.

PMID- 11585597
TI  - Quantitative evidence for multiple widespread representations of individual
      muscles in the cat motor cortex.
AB  - We sought to determine why a given muscle appears represented in widespread loci
      in the motor cortex (MCx). To this end, we microstimulated every 500 microm along
      medio-lateral rows and recorded the evoked electromyographic (EMG) responses of
      up to a dozen forelimb muscles of the cat. A consistent finding in all animals
      studied was that along a given row, distal muscle responses could be elicited
      from medially situated cortical loci and conversely, proximal muscles responses
      from laterally situated cortical loci. In many such cases, the evoked EMG
      responses were such that the largest responses from a distal muscle were obtained
      by stimulation at a medially situated point and those of a proximal muscle from a
      laterally situated point. A Spearman correlation analysis showed that there was
      no correlation between cortical position and where the peak response of a given
      muscle occurred. These quantitative results strongly support the view that in the
      forelimb area of the cat MCx there exists widespread 'colonies' of corticospinal
      neurons with common spinal cord targets.

PMID- 11585598
TI  - Chromosome 12 and late-onset Alzheimer's disease.
AB  - Alzheimer's disease is a complex neurodegenerative disorder, characterized by
      cognitive decline and distinctive neuropathology. Using large extended families
      with multiple affected, we found that three markers on chromosome 12 were linked
      with late-onset Alzheimer's disease. These markers were downstream from the gene
      for alpha-2 macroglobulin. It is likely that multiple genes will be identified
      either as risk factors or as causative agents for late-onset Alzheimer's disease.

PMID- 11585599
TI  - Evaluation of the gamma-synuclein gene in German Parkinson's disease patients.
AB  - Mutations in the alpha-synuclein gene are responsible for an autosomal-dominantly
      inherited form of Parkinson's disease (PD) and alpha-synuclein was found to be
      the major component of Lewy bodies in PD. Because of the high homology to alpha
      synuclein and the abundance in neuronal tissues, we investigated the gamma
      synuclein gene in PD. We analyzed 262 German PD patients and 179 healthy German
      controls via two polymorphisms in the gamma-synuclein gene. No significant
      differences in the allelic or genotypic distributions of the investigated
      polymorphisms were observed between patients and controls. In addition no
      evidence for an increased risk of combined genotypes of polymorphisms in the
      gamma-synuclein and the alpha-synuclein gene was found. Therefore, our results do
      not support a major role of the gamma-synuclein gene in PD.

PMID- 11585602
TI  - A dynamic and spatial model with migration generating the log-Gaussian field of
      population densities.
AB  - A spatial version of a dynamic population model leading to the lognormal
      distribution is defined. The model establishes relations between the joint
      spatial and temporal autocorrelation and biological concepts like environmental
      stochasticity, migration and strength of local density-regulation. The model is
      generalized to describe communities of species leading to a dynamic and spatial
      lognormal species abundance model with migration.

PMID- 11585601
TI  - A competition model with dynamically allocated inhibitor production.
AB  - The chemostat is a basic model for competition in an open system and a model for
      the laboratory bio-reactor (CSTR). Inhibitors in open systems are studied with a
      view of detoxification in natural systems and of control in bio-reactors. This
      study allows the amount of resource devoted to inhibitor production to depend on
      the state of the system. The feasibility of one dependence is provided by quorum
      sensing. In contrast to the constant allocation case, a much wider set of
      outcomes is possible including interior, stable rest points and stable limit
      cycles. These outcomes are important contrasts to competitive exclusion or
      bistable attractors that are often the outcomes for competitive systems. The
      model consists of four non-linear ordinary differential equations and computer
      software is used for most of the stability calculations.

PMID- 11585603
TI  - Capillary supply regions.
AB  - The diffusion and consumption of substrate from capillaries are basic in human
      physiology. The general solution for the concentration in a region containing
      many parallel non-homogeneous capillaries is found. Except in very special cases,
      capillary supply regions cannot be approximated by Krogh's cylinder or Voronoi
      polygonal cylinders.

PMID- 11585604
TI  - Between-species variation in the development of hand preference among macaques.
AB  - This research examined between-species variation in the development of hand
      preference among Macaca. Specifically, we examined hand preference using
      juveniles and adults of three macaque species that differ in social and reactive
      tendencies in order to examine whether the correlation between temperament and
      handedness that has been noted within Macaca mulatta occurs between closely
      related species. Each of the species studied exhibited a different pattern of
      hand preference development. Both juvenile and adult M. mulatta exhibited group
      level left-hand bias. Juvenile Macaca nemestrina were not biased towards either
      hand at the group-level, whereas adults exhibited a group-level left-hand bias.
      Neither juvenile nor adult Macaca fascicularis exhibited manual bias at the group
      level. Analysis of variance indicated statistically significant main effects of
      species and age class on hand preference measures. Post-hoc analysis indicated
      greater use of the left- versus right-hand, and greater hand preference strength
      independent of direction, among M. mulatta and M. nemestrina than among M.
      fascicularis, and among adults than among juveniles. These results indicate
      significant between-species variation in the development of hand preference
      within the genus Macaca, and are inconsistent with any one single-factor theory
      yet offered to explain the etiology of primate laterality. We hypothesize that
      the relationship between handedness and temperament that has been shown within M.
      mulatta may generalize across closely related primate species.

PMID- 11585605
TI  - Regulation of grasping forces during bimanual in-phase and anti-phase
      coordination.
AB  - When a hand-held object is moved, grip force is adapted in an anticipatory manner
      to load force due to a dynamic coupling between both forces. The present study
      addressed the issue of grip-load force regulation when moving rhythmically two
      hand-held objects in the vertical dimension, and more specifically the divergence
      of force control when performing according to the in-phase versus anti-phase
      mode. Results revealed that grip-load force ratio profiles were similar in both
      bimanual conditions. That is, force ratio was not constant throughout the
      movement cycles but followed a fairly regular pattern with maxima and minima,
      attained at upward and downward hand positions, respectively. However, anti-phase
      patterns showed an increased maximum grip-load force ratio as compared to in
      phase patterns, whereas the latter did not differ from unimanual movements. The
      magnification of maximum force ratio during anti-phase movements suggests that
      rescaling occurred. This is likely due to the complexity of the anti-phase mode
      that necessitates increased monitoring and attention relative to the other
      performance conditions, creating a coordinative situation that imposes an
      additional degree of uncertainty. Therefore, the safety margin is amplified
      during anti-phase movements, probably as a strategy to prevent a potential
      destabilization of the grip during an asymmetrical load condition. Accordingly,
      these findings also demonstrate that grip-load force regulation is more
      proficiently controlled during bimanual in-phase than anti-phase movements.
      Herewith, the data add content to earlier work illustrating kinematic
      dissimilarities between both coordination modes.

PMID- 11585606
TI  - Activational effects of testosterone on cognitive function in men.
AB  - OBJECTIVES: The effect of testosterone (T) on sexual function in men is well
      established. However, less is known about its effects on cognitive function. The
      aim of this study is to investigate the relationship between T levels and sex
      typed cognitive abilities in both eugonadal and hypogonadal men. DESIGN: A single
      blind placebo-controlled design was employed in this study. METHODS: Thirty
      healthy eugonadal men and seven hypogonadal men participated in the study.
      Eugonadal men were randomised into one of two treatment regimens: (1) active
      group--receiving 200 mg of T enanthate i.m. weekly for 8 weeks (raising T levels
      into the supraphysiological range) or (2) placebo group--receiving 200 mg of
      sodium chloride i.m. weekly for 8 weeks. The hypogonadal group received the
      physiological replacement dose of 200 mg T enanthate i.m. bi-weekly for 8 weeks.
      All groups underwent a battery of neuropsychological tests and had circulating T
      measured at baseline, and at weeks 4 and 8 during treatment. RESULTS: A
      significant time by group interaction effect was found in the measure of spatial
      ability (i.e., block design test) indicating that the active group's performance
      declined significantly at week 4, compared to placebo group (F(4,64)=3.78,
      P<0.01). Conversely, the active group performed significantly better than the
      placebo group in the measure of verbal fluency (i.e., the Controlled Oral Word
      Association Test) at week 4 (F(4,64)=2.54, P<0.05). No significant changes were
      found on any of the other tests. Generally, the hypogonadal group performed less
      well than the eugonadal groups on all tests. CONCLUSIONS: These results offer
      support to the notion that increased T has a differential effect on cognitive
      function, inhibiting spatial abilities while improving verbal fluency in
      eugonadal men.

PMID- 11585607
TI  - Interhemispheric visual matching in the split brain.
AB  - Three split-brained subjects, one (N.G.) with full forebrain commissurotomy and
      two (V.P. and J.W.) with callosotomy, made same-different judgments about pairs
      of visual stimuli that were flashed either unilaterally or bilaterally. In
      separate blocks of trials, the stimuli could differ in luminance, size, or color.
      In the bilateral condition, only J.W. scored above chance, and only minimally, on
      the luminance and size tasks, and none of the subjects scored above chance on the
      color task. Accuracy was generally much higher, especially for V.P. and J.W.,
      when the stimuli were unilateral. These results confirm that there is little or
      no interhemispheric transfer of the visual attributes of luminance, size or color
      in the split brain.

PMID- 11585608
TI  - Deficit of auditory space perception in patients with visuospatial neglect.
AB  - There have been many studies of visuospatial neglect, but fewer studies of
      neglect in relation with other sensory modalities. In the present study we
      investigate the performance of six right brain damaged (RBD) patients with left
      visual neglect and six RBD patients without neglect in an auditory spatial task.
      Previous work on sound localisation in neglect patients adopted measure of sound
      localisation based on directional motor responses (e.g., pointing to sounds) or
      judgement of sound position with respect to the body midline (auditory midline
      task). However, these measures might be influenced by non-auditory biases related
      with motor and egocentric components. Here we adopted a perceptual measure of
      sound localisation, consisting in a verbal judgement of the relative position
      (same or different) of two sequentially presented sounds. This task was performed
      in a visual and in a blindfolded condition. The results revealed that sound
      localisation performance of visuospatial neglect patients was severely impaired
      with respect to that of RBD controls, especially when sounds originated in
      contralesional hemispace. In such condition, neglect patients were always unable
      to discriminate the relative position of the two sounds. No difference in
      performance emerged as a function of the visual condition in either group. These
      results demonstrate a perceptual deficit of sound localisation in patients with
      visuospatial neglect, suggesting that the spatial deficits of these patients can
      arise multimodally for the same portion of external space.

PMID- 11585609
TI  - Visual control of isometric force in Parkinson's disease.
AB  - The current article reports an investigation of the influence of visual feedback
      on force production in Parkinson's disease (PD) that required subjects to
      maintain a constant amount of isometric force with their index finger and thumb
      with and without visual feedback. Eight PD and eight matched control subjects
      produced force at 5, 25 and 50% of their maximal voluntary contraction for 20 s.
      In conditions of full vision, the force trajectory and force target were viewed
      on the computer monitor. In the no visual feedback condition, visual feedback of
      the force trajectory vanished after the initial 8 s of the trial. The results
      showed that under the vision condition PD subjects produced levels of maximal and
      submaximal force that were similar to controls. Approximately 1.5-2.5 s following
      the removal of visual feedback, the force level in both subject groups decreased
      to steady-state levels. There was no difference in the time between visual
      feedback removal and the beginning of force decay in PD. There was a larger
      amount and faster rate of force decay after visual feedback removal in PD
      subjects compared to the controls. It is proposed that the increased force decay
      in PD does not result from sensory reflex deficits but from higher order sensory
      motor memory processes.

PMID- 11585610
TI  - Cognitive resources during sentence processing in Alzheimer's disease.
AB  - This study assessed sentence comprehension in Alzheimer's disease (AD) while
      minimizing executive resource demands. AD patients (n=17) and healthy elderly
      control subjects (n=17) were asked to detect a word in a sentence. Unbeknownst to
      subjects, the target word at times followed an incorrect grammatical or semantic
      agreement. Control subjects took significantly longer to respond to a target word
      when it immediately followed an agreement violation compared to a coherent
      agreement, a difference that was not evident when the target word followed the
      agreement by several syllables. AD patients did not demonstrate a discrepancy
      between a violation and a coherent agreement in the immediate vicinity of the
      agreement, but demonstrated a significant delay in their response to a target
      word when it followed an agreement violation--particularly a violation of a
      grammatical agreement--by several syllables. Analyses of individual patient
      performance profiles revealed the pattern of delayed sensitivity to agreements in
      a majority of AD patients. Correlation and regression analyses associated AD
      patients' sensitivity to agreement violations over an abnormally delayed time
      course with a measure of inhibitory control, although weaker associations were
      also evident with measures of planning and short-term memory. We hypothesize that
      difficulty understanding grammatically complex sentences in AD is related to
      slowed information processing speed that restricts the timely construction of a
      sentence's structure and limits inhibition of canonical sentence interpretations
      such as first-noun-is-subject.

PMID- 11585611
TI  - Imitation of gestures by disconnected hemispheres.
AB  - PU's corpus callosum was severed as a sequel of bleeding from an arteriovenous
      malformation. The lesion affects the truncus and the splenium and caused
      somatosensory and visual disconnection of the hemispheres. On clinical testing
      PU's left hand was apraxic for pantomime of object use but not for imitation. By
      contrast, when stimuli for imitation of meaningless hand and finger postures were
      presented tachistocopically to either the left or the right visual field, both
      hemispheres turned out to be apraxic in different ways. Imitation of hand
      postures was perfect for right-handed imitation of stimuli presented to the left
      hemisphere but defective in all other conditions. Imitation of finger postures
      was below the normal range in all conditions initially, but improved to normality
      for right-hand imitation of stimuli presented to the left hemisphere after
      repeated testing. After successful imitation of gestures presented to the left
      hemisphere PU commented that he imitated without really seeing the stimulus by
      "formulating the unseen", whereas after presentation to the right hemisphere he
      felt that he saw the stimulus but could not imitate. We propose that imitation of
      meaningless gestures affords a coding of gestures with reference to knowledge
      about body parts which can be applied only by the left hemisphere. Imitation of
      finger postures puts additional demands on fine grained visuospatial
      discrimination which necessitates a contribution by the right hemisphere.

PMID- 11585612
TI  - Mirror images and unilateral spatial neglect.
AB  - Responding correctly to a mirror image requires the creation of a rather peculiar
      form of dual representation. Mirror agnosia and mirror ataxia, i.e. a deficit in
      reaching an object reflected in a mirror, have been reported to be associated
      with parietal lobe lesions. This prospective study was conducted to investigate
      the capacity of subjects with neglect to identify the mirror image nature of
      visual information. Four consecutive brain-damaged patients with neglect,
      selected on the basis of specific criteria, and four control subjects performed
      grasping and object displacement tests under two response conditions (normal
      mirror and inverted mirror). Video recordings of the tests were analyzed to
      assess performance using the following criteria: (i) direction of the arm
      movement during the initial phase of movement, (ii) number of corrections of the
      hand position before grasping. The control subjects successfully grasped the
      objects in both experimental conditions. The patients (1) neglected the
      contralesional space, grasping objects correctly in the ipsilesional space
      (normal mirror condition) and (2) neglected the ipsilesional space, grasping
      correctly objects in the contralesional space (inverted mirror). Controls used
      real object-centered correction clues to modify the position and direction of
      their hand movement. The patients only produced horizontal displacements of the
      upper limb in the "healthy" and neglected space. These results suggest that
      patients with neglect do not use the same clues and do not modify their
      procedures as they cannot recalibrate their spatial representations. These
      differences concerned non-mirror-image clues and directional and positional as
      well as attentional vectors. Theoretical and rehabilitative implications are
      discussed.

PMID- 11585613
TI  - Bihemispheric sensitivity to sentence anomaly.
AB  - This study investigated cerebral asymmetries in sensitivity to sentence-level
      semantic anomaly. To separate the effects of anomalous message processing from
      those attributable to low sentence constraint, low-constraint sentence-fragment
      primes were followed by target words presented to the left or right visual
      fields. When completed by the target word, the sentences represented either
      normal or anomalous messages; in addition, one-half of the sentence primes
      contained a word strongly related to the target. Targets presented to both the
      left and right visual fields were advantaged by the presence of a related word,
      and disadvantaged by the presence of a semantically anomalous message. Contrary
      to some previous claims, this result implies that the right hemisphere can
      construct some message-level interpretations from sentences, such that semantic
      anomaly is registered, even if finer gradations of sentence constraint are not.
      This rudimentary integration of word meanings in sentences may provide a
      scaffolding for right hemisphere discourse processing. In light of these
      findings, we propose a revised view of left/right hemisphere differences in the
      processes used to interpret sentence meaning.

PMID- 11585614
TI  - Changes in event-related potentials in a three-stimulus auditory oddball task
      after mild head injury.
AB  - Previous research has demonstrated changes in event-related potentials in a
      variety of cognitive tasks after severe closed head injury. We sought to
      establish if similar changes were present in patients who had sustained only
      apparently mild head injury (MHI) by recording event-related potentials in a
      group of 24 mild head injured and 24 control participants during a three-stimulus
      auditory target detection task. For this "oddball" task participants were
      required to press a button every time they heard a rare target tone and to ignore
      rare novel sounds and frequent non-target tones. Neuropsychological test results
      indicated that the mild head injured group had mild memory and attention
      impairments. Analysis of behavioural performance on the three-stimulus "oddball"
      task showed no difference in reaction times or error rates between the two
      groups. Target condition N2 deflections appeared to be larger in the mild head
      injured but peak amplitude measures revealed that this effect was not
      significant. There were no significant differences in the amplitude or latency of
      the P3b evoked by target stimuli or the P3a evoked by novel stimuli. However, a
      putative "O-wave" or "reorienting negativity" following the P3a was more negative
      in the mild head injured group suggesting increased activation of components of
      the attention network. These findings lend support to the hypothesis that MHI can
      cause subtle cognitive impairments that are associated with abnormal allocation
      of attention resources in the context of normal behavioural performance.

PMID- 11585615
TI  - Routes to reading: a report of a non-semantic reader with equivalent performance
      on regular and exception words.
AB  - This study reports the case of a stroke patient, EW, who had severely-impaired
      comprehension of written words but could read aloud regular and exception words,
      non-words and sentences flawlessly. EW's auditory comprehension was also
      impaired. It is argued that these results support a three-route model of reading,
      where the phonological output lexicon can be activated directly from the
      orthographic input lexicon, as her reading performance did not conform to the
      pattern that would be expected from a combination of lexical-semantic and
      sublexical processing alone. It is suggested that normal reading may be better
      conceptualised as a summation of three routes, rather than two.

PMID- 11585616
TI  - Are there sex differences in the brain basis of literacy related skills? Evidence
      from reading and spelling impairments after early unilateral brain damage.
AB  - Reading and spelling performance was analysed for a sample of 45 children with
      unilateral brain damage. Boys showed impairments only when the lesion was on the
      left, while girls showed no significant impairments when either hemisphere was
      affected. The results support the hypothesis that specialised substrates, which
      underlie literacy acquisition, have limited plasticity and may be more strongly
      lateralised to the left hemisphere in males than in females.

PMID- 11585617
TI  - Tumor necrosis factor(alpha) and insulin-like growth factor-I in the brain: is
      the whole greater than the sum of its parts?
AB  - The cytokine tumor necrosis factor(alpha) (TNFalpha) and the hormone insulin-like
      growth factor-I (IGF-I) have both been shown to regulate inflammatory events in
      the central nervous system (CNS). This review summarizes the seemingly
      independent roles of TNFalpha and IGF-I in promoting and inhibiting
      neurodegenerative diseases. We then offer evidence that the combined effects of
      IGF-I and TNFalpha on neuronal survival can be vastly different when both
      receptors are stimulated simultaneously, as is likely to occur in vivo. We
      propose the framework of a molecular model of hormone-cytokine receptor cross
      talk in which disparate cell surface receptors share intracellular substrates
      that regulate neuronal survival.

PMID- 11585618
TI  - Polygenic control of autoimmune peripheral nerve inflammation in rat.
AB  - Experimental autoimmune neuritis (EAN) is the principal animal model for Guillain
      Barre syndrome (GBS), an inflammatory disease of the peripheral nervous system.
      Little is known on the genetic regulation of these diseases. We provide the first
      genetic linkage analysis of EAN. Susceptibility to EAN in a rat F2 population
      segregated with high levels of anti-PNM IgG, as well as IgG2b and IgG2c isotype
      levels, which support that disease genes regulate preferential Th1/Th2
      differentiation. Linkage analysis demonstrated co-localization of EAN loci with
      reported susceptibility loci for experimental arthritis and/or encephalomyelitis
      and a new region on chromosome 17. Further dissection of these loci may disclose
      disease pathways in GBS.

PMID- 11585619
TI  - Blood-retinal barrier breakdown in experimental coronavirus retinopathy:
      association with viral antigen, inflammation, and VEGF in sensitive and resistant
      strains.
AB  - Intraocular coronavirus inoculation results in a biphasic retinal disease in
      susceptible mice (BALB/c) characterized by an acute inflammatory response,
      followed by retinal degeneration associated with autoimmune reactivity. Resistant
      mice (CD-1), when similarly inoculated, only develop the early phase of the
      disease. Blood-retinal barrier (BRB) breakdown occurs in the early phase in both
      strains, coincident with the onset of inflammation. As the inflammation subsides,
      the extent of retinal vascular leakage is decreased, indicating that BRB
      breakdown in experimental coronavirus retinopathy (ECOR) is primarily due to
      inflammation rather than to retinal cell destruction. Vascular endothelial growth
      factor (VEGF) is upregulated only in susceptible mice during the secondary
      (retinal degeneration) phase.

PMID- 11585620
TI  - Interleukin-17 stimulates inducible nitric oxide synthase activation in rodent
      astrocytes.
AB  - The effect of interleukin-17 (IL-17) on production of nitric oxide (NO) in rodent
      astrocytes was investigated. While IL-17 by itself did not induce NO production,
      it caused a dose-dependent enhancement of IFN-gamma-triggered NO synthesis in
      both mouse and rat primary astrocytes. In contrast, IL-17 was unable to stimulate
      NO synthesis in either murine or rat macrophages. IFN-gamma-triggered expression
      of mRNA for iNOS, but not for its transcription factor interferon regulatory
      factor-1 (IRF-1), was markedly elevated in IL-17-treated astrocytes. The
      induction of iNOS mRNA by IL-17 in IFN-gamma-pretreated astrocytes was abolished
      by antagonists of nuclear factor-kappaB (NF-kappaB) activation--a proteasome
      inhibitor MG132 and an antioxidant agent PDTC, as well as with specific p38 MAP
      kinase inhibitor SB203580. While IL-17 stimulated both IL-1beta and IL-6
      production in astrocytes, only IL-1 was partly responsible for IL-17-induced NO
      release. Finally, IL-17 synergized with exogenous IL-1beta and TNF-alpha for
      astrocyte NO production. Having in mind a well-known neurotoxic action of NO,
      these results suggest a possible role for IL-17 in the inflammatory diseases of
      the CNS.

PMID- 11585621
TI  - Tumor necrosis factor receptor fragment attenuates interferon-gamma-induced non
      REM sleep in rabbits.
AB  - Although the somnogenic actions of interferon-alpha (IFNalpha) and IFNbeta have
      been reported, the sleep effects of IFNgamma remained unknown. Thus, we
      investigated the effects of intracerebroventricular injection of human IFNgamma
      on sleep in rabbits. IFNgamma dose-dependently increased nonrapid eye movement
      sleep (NREMS), electroencephalographic slow wave activity and brain temperature
      (Tbr). These effects were markedly attenuated after the heat treatment of
      IFNgamma. IFNgamma suppressed rapid eye movement sleep if given during the light
      period, but not if given at dark onset. Although a tumor necrosis factor receptor
      fragment did not affect any sleep parameters when given at dark onset, it
      significantly attenuated IFNgamma-induced NREMS and Tbr. These data suggest that
      IFNgamma may be involved in the sleep responses during infection. Further,
      IFNgamma may have a synergistic interaction with intrinsic TNFalpha in the brain.

PMID- 11585622
TI  - T-cell-based immunity counteracts the potential toxicity of glutamate in the
      central nervous system.
AB  - Injuries to the central nervous system (CNS) evoke self-destructive processes,
      which eventually lead to a much greater loss of tissue than that caused by the
      trauma itself. The agents of self-destruction include physiological compounds,
      such as glutamate, which are essential for the proper functioning of the CNS, but
      become cytotoxic when their normal concentrations are exceeded. The CNS is
      equipped with buffering mechanisms that are specific for each compound. Here we
      show, using Balb/c mice (a strain resistant to induction of experimental
      autoimmune encephalomyelitis), that after intravitreal injection of any
      concentration of glutamate (a neurotransmitter that becomes toxic when in excess)
      or ammonium-ferrous sulfate hexahydrate (which increases the formation of toxic
      oxygen species), the loss of retinal ganglion cells in mice devoid of mature T
      cells (nude mice) is significantly greater than in matched wild-type controls. We
      further show that this outcome can be partially reversed by supplying the T cell
      defective mice with splenocytes derived from the wild-type mice. The results
      suggest that potentially toxic physiological compounds, when present in excessive
      amounts, can recruit and activate a T-cell-dependent self-protective immune
      mechanism. This may represent a prototype mechanism for the physiological
      regulation of potentially destructive CNS events by T-cell-mediated immune
      activity, when the local buffering mechanisms cannot adequately cope with them.

PMID- 11585623
TI  - Cuprizone and piperonyl butoxide, proposed inhibitors of T-cell function,
      attenuate experimental allergic encephalomyelitis in SJL mice.
AB  - Multiple sclerosis (MS) and its animal model, experimental allergic
      encephalomyelitis (EAE), are autoimmune demyelinating diseases with autoreactive
      T-cells acting as important mediators of pathogenesis. Cuprizone, a copper
      chelator, and piperonyl butoxide (PBO), a pesticide synergist, are implicated to
      inhibit T-cell activation and function. The purpose of this study was to assess
      whether either of these agents would suppress PLP-peptide-induced EAE in the SJL
      mouse. Indeed, treatment with cuprizone beginning 1 week prior to disease
      induction, and PBO administration from days 1 to 9 of EAE, significantly
      attenuated EAE clinical severity. Furthermore, both agents decreased blood
      CD4+/CD8+ ratios, and reduced signs of chronic graft vs. host disease (GVHD)
      indicating attenuation of an immune T-cell response. These results suggest that
      cuprizone and PBO suppress EAE and use of these agents will provide insights into
      the mechanisms of T-cell mediated diseases.

PMID- 11585624
TI  - AIF-1 expression defines a proliferating and alert microglial/macrophage
      phenotype following spinal cord injury in rats.
AB  - Microglial cells are among the first and dominant cell types to respond to CNS
      injury. Following calcium influx, microglial activation leads to a variety of
      cellular responses, such as proliferation and release of cytotoxic and
      neurotrophic mediators. Allograft inflammatory factor-1, AIF-1 is a highly
      conserved EF-handed, putative calcium binding peptide, associated with microglia
      activation in the brain. Here, we have analyzed the expression of AIF-1 following
      spinal cord injury at the lesion site and at remote brain regions. Following
      spinal cord injury, AIF-1+ cells accumulated in parenchymal pan-necrotic areas
      and perivascular Virchow-Robin spaces. Subsequent to culmination at day 3--a
      situation characterized by infiltrating blood borne macrophages and microglia
      activation--AIF-1+ cell numbers decreased until day 7. In remote areas of
      Wallerian degeneration and delayed neuronal death, a more discrete and delayed
      activation pattern of AIF-1+ microglia/macrophages reaching maximum levels at day
      14 was observed. There was a considerable match between AIF-1+ cells and PCNA
      (proliferating cell nuclear antigen) or Ki-67+ labeled cells. AIF-1 expression
      preceded the expression of ED1, thus indicating a pre-phagocytic role. It appears
      that AIF-1+ microglia/macrophages are among the earliest cells to respond to
      spinal cord injury. Our results suggest a role of AIF-1 in the initiation of the
      early microglial response leading to activation and proliferation essential for
      the acute response to CNS injury. AIF-1 might modulate microgliosis influencing
      the efficacy of tissue debris removal, myelin degradation, recruitment of
      oligodendrocytes and re-organisation of the CNS architecture.

PMID- 11585625
TI  - Experimental allergic myositis in SJL/J mouse. Reappraisal of immune reaction
      based on changes after single immunization.
AB  - SJL/J mice have been subjected to immunization with wide varieties of antigens to
      produce models of autoimmune disorders including experimental myositis. They also
      have a defect in dysferlin gene and spontaneously develop muscle fiber
      degeneration, a condition akin to limb-girdle type muscular dystrophy and Miyoshi
      myopathy. To know whether muscle inflammation of SJL mice after immunization with
      muscle fractions really represents immune-mediated myositis or no more than an
      epiphenomenon of muscle degeneration due to dysferlin defect, we studied
      immunological parameters after immunization with rabbit myosin B fraction.
      Initial infiltration of macrophages and CD4+ lymphocytes on day 11 was followed
      by increase in number of CD8+ cells. Such increase was not observed in the
      nontreated and adjuvant controls. Some infiltrating cells were interferon gamma
      (IFN-gamma) positive. Furthermore, increased expression of the signal transducers
      and activator of transcription 1 (STAT-1) and interferon regulatory factor 1 (IRF
      1) mRNA was shown in the first 2 weeks. These results indicate Th1 system
      activity in the muscle, rather than simple dysferlin deficiency, particularly 1-3
      weeks after immunization. Thus it is concluded that an immune-mediated myositis
      is taking place at this stage. This model can be helpful in understanding
      pathomechanisms involved in the early stage of human myositides. It has also
      important implications concerning immune reactions associated with
      transplantation or gene therapy for muscular dystrophies.

PMID- 11585626
TI  - Catecholamines in murine bone marrow derived mast cells.
AB  - Cultured murine bone marrow derived mast cells (BMMC) were found to store high
      levels of dopamine (3753+/-844 pg/10(7) cells) and occasionally produce
      norepinephrine and epinephrine. The catecholamine synthesis inhibitor, alpha
      methyl-para-tyrosine, decreased intracellular catecholamine concentrations, and
      activation with ionomycin stimulated dopamine release. Neither dopaminergic
      receptor antagonists nor exogenous dopamine < or =10 microM affected IL-3-induced
      cell proliferation. High exogenous dopamine (20-100 microM) decreased
      proliferation and increased apoptosis, and the anti-oxidant ascorbic acid
      prevented these effects. Increased expression of the anti-apoptotic factor Bcl-2
      or loss of pro-apoptotic Bax expression attenuated dopamine-induced apoptosis,
      suggesting the apoptosis proceeds through a mitochondrial pathway.

PMID- 11585627
TI  - Defective CD4T cell priming and resistance to experimental autoimmune
      encephalomyelitis in TNF-deficient mice due to innate immune hypo-responsiveness.
AB  - We report here that tumor necrosis factor (TNF) deficiency causes innate hypo
      responsiveness to a broad range of bacterial or viral constituents. In vivo hypo
      responsiveness of TNF-deficient mice to mycobacteria results in defective CD4+ T
      cell priming to antigens administered in complete Freund's adjuvant (CFA). This
      deficiency is restored by supplementary mycobacteria. Furthermore, we show that
      even when self-reactive CD4+ T cell priming is fully restored, susceptibility of
      TNF-deficient mice to experimental autoimmune encephalomyelitis (EAE) depends on
      the co-administered pertussis toxin (PTx). TNF-deficient mice are completely
      resistant to EAE at sub-optimal doses of PTx, while supplementary PTx restores
      susceptibility. Therefore, TNF shows distinct functions in linking innate
      responsiveness to CD4+ T cell priming and to the induction of autoimmune disease.

PMID- 11585628
TI  - Altered inflammatory response and increased neurodegeneration in metallothionein
      I+II deficient mice during experimental autoimmune encephalomyelitis.
AB  - Metallothionein-I+II (MT-I+II) are antioxidant, neuroprotective proteins, and in
      this report we have examined their roles during experimental autoimmune
      encephalomyelitis (EAE) by comparing MT-I+II-knock-out (MTKO) and wild-type mice.
      We herewith show that EAE susceptibility is higher in MTKO mice relatively to
      wild-type mice, and that the inflammatory responses elicited by EAE in the
      central nervous system (CNS) are significantly altered by MT-I+II deficiency.
      Thus, during EAE the MTKO mice showed increased macrophage and T-lymphocytes
      infiltration in the CNS, while their reactive astrogliosis was significantly
      decreased. In addition, the expression of the proinflammatory cytokines
      interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha elicited by EAE
      was further increased in the MTKO mice, and oxidative stress and apoptosis were
      also significantly increased in MTKO mice compared to normal mice. The present
      results strongly suggest that MT-I+II are major factors involved in the
      inflammatory response of the CNS during EAE and that they play a neuroprotective
      role in this scenario.

PMID- 11585629
TI  - The effect of immunosuppressive protocols on spontaneous CNS remyelination
      following toxin-induced demyelination.
AB  - Glial cell transplantation is a potential therapy for human demyelinating
      disease, though obtaining large numbers of human myelinating cells for
      transplantation remains a major stumbling block. Autologous transplantation is
      currently not possible, since the adult human CNS is not a good source of
      oligodendrocyte precursors, and long-term immunosuppression of engrafted
      allogeneic or xenogeneic cells is therefore likely to be necessary.
      Immunosuppressive drugs may need to be used in situations where more recent,
      active areas of demyelination are undergoing endogenous remyelination. It is
      therefore pertinent to establish the extent to which immunosuppressive protocols
      will suppress spontaneous remyelination. In order to investigate this issue, we
      created demyelinating lesions in the spinal cord of adult rats and compared the
      extent of remyelination in animals receiving different immunosuppressive
      treatments. In animals given only cyclosporin A, there was no difference in the
      extent of either Schwann cell or oligodendrocyte remyelination of ethidium
      bromide-induced demyelinating lesions. However, in animals given
      cyclophosphamide, either alone or in combination with cyclosporin, there was a
      significant reduction in the extent of oligodendrocyte-mediated remyelination.
      These results demonstrate that cyclophosphamide is deleterious to oligodendrocyte
      remyelination and for this reason should be used with caution in patients with
      demyelinating disease.

PMID- 11585630
TI  - Enhanced glial activation and expression of specific CNS inflammation-related
      molecules in aged versus young rats following cortical stab injury.
AB  - Aging is associated with increased glial responsiveness that may enhance the
      brain's susceptibility to injury and disease. To determine whether unique age
      related molecular responses occur in brain injury, we assessed mRNA levels of
      representative central nervous system (CNS) inflammation-related molecules in
      young (3 months) and aged (36 months) Fisher 344/Brown Norwegian F1 hybrid rats
      following cortical stab. Enhanced glial activation in older animals was
      accompanied by increased expression of a subset of inflammation-related mRNAs,
      including IL-1beta, TNFalpha, IL-6, ICAM-1, inducible nitric oxide synthase
      (iNOS), metalloproteinase-9 (MMP-9), and complement 3alpha-chain 1 (C3alpha1).
      Recognition of these age-specific differences may guide development of novel
      treatment regimes for older individuals.

PMID- 11585631
TI  - Assessment of HIV-intrathecal humoral immune response in AIDS-related
      neurological disorders.
AB  - Intrathecal synthesis of IgG directed to HIV antigens was investigated by
      antibody specific index (ASI), affinity-mediated immunoblot (AMI) and Western
      blot (WB) assay in a group of 88 AIDS patients of which 28 with HIV-associated
      neurological disorders (HAND), 13 without associated neurological disorders
      (WAND) and 47 with non-HIV-associated neurological disorders (non-HAND). CD4+
      count was above 50 cells/mm3 (CD4+>50) in 30 and below 50/mm3 (CD4+<50) in 58
      patients, respectively. A significantly higher frequency for CSF complete anti
      gag profile (p<0.001), and for HIV-specific oligoclonal patterns ("mixed"
      pattern=p<0.01) was observed in HAND as compared to patterns from the other
      clinical groups. A decrease in complete anti-env, anti-pol and anti-gag
      reactivity was present in CSF of patients with CD4+<50 as compared to those with
      CD4+>50. Our findings suggest that AIDS appears to be characterized by an anti
      HIV intrathecal humoral immune response which is principally directed to env
      products with a prevalence of oligoclonal patterns and CSF complete anti-gag
      profile in HIV-associated neurological involvement.

PMID- 11585632
TI  - Antibody pattern analysis in the Guillain-Barre syndrome and pathologic controls.
AB  - The Guillain-Barre Syndrome (GBS) is an acute inflammatory
      polyneuroradiculopathy, which is considered to be caused by autoimmune processes.
      A number of single antigenic structures has been suggested to be targeted by the
      immune system, but a conclusive etiological concept has not been evolved yet. We
      compared reactions of sera from GBS patients (N=28) and from both two
      pathological control groups, 25 Multiple sclerosis (MS) patients and 32 patients
      with other non-inflammatory peripheral polyneuropathies (ONP) and from sex- and
      age-matched healthy controls (N=30). Porcine peripheral nerve proteins were used
      as antigens in a Western blot procedure. The blots were analysed by densitometry,
      and a multivariate statistical comparison of the antibody repertoires was carried
      out. Antibody patterns of GBS patients differed significantly (p<0.001) from each
      of the control groups. Discriminant analysis indicated that the discrimination
      resulted from pattern differences of specific regions of the blots containing
      proteins with estimated molecular weights of 58-64 and 28-29 kDa. We conclude
      that statistical analysis of antibody patterns may be helpful both in clinical
      diagnosis and in further research concerning the pathogenesis of GBS.

PMID- 11585633
TI  - Tc1/Tc2 and Th1/Th2 balance in Asian and Western types of multiple sclerosis,
      HTLV-I-associated myelopathy/tropical spastic paraparesis and hyperIgEaemic
      myelitis.
AB  - CD8+ T cells, like CD4+ T cells, can differentiate into at least two subsets with
      distinct cytokine patterns: Tc1 cells produce Th1-like cytokines and Tc2 cells
      produce Th2-like cytokines. To clarify the immunopathological roles of Tc1 and
      Tc2 cells in central nervous system (CNS) inflammation, we examined intracellular
      cytokines in CD8+ and CD4+ T cells by flow cytometry and analyzed the Tc1/Tc2
      balance as well as the Th1/Th2 balance in 80 patients with various CNS
      inflammatory diseases, including 20 with optico-spinal multiple sclerosis (OS
      MS), 21 with conventional MS (C-MS), 22 with human T-lymphotropic virus type I
      (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 17 with
      hyperIgEaemic myelitis. Twenty-two healthy subjects were also examined as
      controls. Patients with OS-MS showed a significantly higher percentage of INF
      gamma+IL-4- CD8+ T cells as well as CD4+ T cells and a significantly higher
      intracellular interferon-gamma (IFN-gamma)/interleukin-4 (IL-4) ratio both in
      CD8+ and CD4+ T cells throughout the relapse and remission phases than the
      healthy controls. Furthermore, the patients with OS-MS showed a significantly
      lower percentage of INF-gamma-IL-4+ CD4+ T cells as well as CD8+ T cells during
      the relapse phase than the healthy controls. On the other hand, the patients with
      C-MS showed a significantly higher percentage of IFN-gamma-IL-4+ CD8+ T cells in
      addition to more IFN-gamma+IL-4- CD4+ T cells during the relapse phase than the
      healthy controls. The HAM/TSP patients showed a significantly higher percentage
      of INF-gamma+IL-4- CD8+ T cells and a significantly higher intracellular IFN
      gamma/IL-4 ratio in CD8+ T cells than the healthy controls. In contrast, in
      hyperIgEaemic myelitis, in addition to a significantly lower intracellular IFN
      gamma/IL-4 ratio in CD4+ T cells, a tendency toward a lower intracellular IFN
      gamma/IL-4 ratio in CD8+ T cells in comparison to the healthy controls was
      observed. These results clarified for the first time the distinct Tc1/Tc2 balance
      in each disease condition as follows: Tc1 cell response is predominant in OS-MS
      and HAM/TSP, while Tc2 cell response is predominant in hyperIgEaemic myelitis and
      at relapse phase of C-MS. Furthermore, our results suggest that CD8+ T cells play
      an adjunctive role in disease induction and the clinical course of MS.

PMID- 11585634
TI  - Guillain-Barre syndrome serum and anti-Campylobacter antibody do not exacerbate
      experimental autoimmune neuritis.
AB  - To investigate whether antibodies are pathogenic in Guillain-Barre syndrome
      (GBS), we injected pre-treatment serum from 11 GBS patients intraperitoneally
      into rats in which the blood-nerve barrier had been opened by induction of mild
      adoptive transfer experimental autoimmune neuritis. There was no significant
      clinical, neurophysiological or pathological difference between rats receiving
      GBS serum compared with those receiving control serum, except that GBS serum
      caused minor excess weight loss. Murine monoclonal antibody to Campylobacter
      jejuni and gangliosides also did not exacerbate disease. This experiment failed
      to show antibody-mediated disease exacerbation and so does not support an
      antibody-mediated mechanism in GBS.

PMID- 11585635
TI  - Beta (CC)-chemokines as modulators of sleep: implications for HIV-induced
      alterations in arousal state.
AB  - Sleep is altered early in the course of HIV infection, before the onset of AIDS,
      indicating effects of the virus on neural processes. Previous observations
      suggest HIV envelope glycoproteins are possible mediators of these responses.
      Because some beta (CC)-chemokine receptors serve as co-receptors for HIV and bind
      HIV envelope glycoproteins, we determined in this study whether selected CC
      chemokine ligands alter sleep and whether their mRNAs are detectable in brain
      regions important for sleep. CCL4/MIP-1beta, but not CCL5/RANTES, injected
      centrally into rats prior to dark onset increased non-rapid eye movements sleep,
      fragmented sleep, and induced fever. mRNA for the chemokine receptor CCR3 was
      detectable under basal conditions in multiple brain regions. These data suggest
      some CC chemokines may also be involved in processes by which HIV alters sleep.

PMID- 11585636
TI  - Increased intrathecal production of apolipoprotein D in multiple sclerosis.
AB  - Apolipoprotein D (apoD) is a small glycoprotein responsible for the local
      transport of small hydrophobic ligands. Within the nervous system, apoD may be an
      acute phase protein that is upregulated in a variety of neuropathological
      conditions and is involved in the removal of lipids during nerve cell
      degeneration and provision of lipids during the regenerative phase. In this
      study, we measured cerebrospinal fluid (CSF) and serum apoD levels in patients
      with multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy
      (CIDP), Guillain-Barre Syndrome (GBS), infectious inflammatory neurological
      diseases (IND) and non-inflammatory neurological diseases (NND). We found that
      mean CSF apoD levels are significantly increased in patients with CIDP/GBS
      reflecting an acute blood-nerve barrier leakage. In contrast, MS is characterized
      by an increased intrathecal apoD release as measured by the apoD index. Thus, the
      results of our study provide the first evidence of an increased intrathecal
      production of apoD in MS. Moreover, we demonstrate that mean apoD indices are
      highest in MS patients at the time of their first clinical exacerbation. CSF apoD
      levels and apoD indices correlate with MS disease duration but not with
      disability or age. Finally, we found that corticosteroid treatment resulted in
      significantly elevated CSF apoD levels.

PMID- 11585637
TI  - The effects of calpain inhibition upon IL-2 and CD25 expression in human
      peripheral blood mononuclear cells.
AB  - Calcium is an important contributor to T cell activation; it is also the major
      factor in the activation of the calcium-activated neutral proteinase, calpain.
      For this reason, we wanted to investigate if calpain has a role in T cell
      activation and what aspects of this activation calpain affects. As measured by
      semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR),
      calpain inhibition decreased interleukin-2 (IL-2) and CD25 mRNA expression in a
      dose-dependent manner, at early time points following the initial activation, and
      over extended periods of time in activated human peripheral blood mononuclear
      cells (PBMCs). Using an enzyme-linked immuno-sorbent assay (ELISA) specific for
      human IL-2, we found that calpain inhibition decreased IL-2 secretion in a dose
      dependent manner, shortly after activation, and continuously over time.
      Inhibiting calpain caused a dose-dependent inhibition of CD25 cell surface
      expression and also inhibited expression shortly after activation and for at
      least 48 h. This study showed that calpain has an integral role in the synthesis
      of the two important T cell activation factors, IL-2 and CD25.

PMID- 11585638
TI  - LPS-induced IL-10 production in whole blood cultures from chronic fatigue
      syndrome patients is increased but supersensitive to inhibition by dexamethasone.
AB  - Several causes have been held responsible for the chronic fatigue syndrome (CFS),
      including an altered hypothalamus-pituitary-adrenal gland (HPA)-axis activity,
      viral infections and a reduced Th1 activity. Therefore, it was investigated
      whether the regulation of IL-10 is different in CFS. LPS-induced cytokine
      secretion in whole blood cultures showed a significant increase in IL-10 and a
      trend towards a decrease in IL-12 as compared with healthy controls. In patients
      and controls, IL-12 secretion was equally sensitive to suppression by
      dexamethasone, whereas IL-10 secretion appeared more sensitive in CFS-patients.
      In controls, IL-10 and IL-12 secretion were inversely correlated with free serum
      cortisol (r=-0.492, p<0.02 and r=-0.434, p<0.05, respectively). In CFS, such an
      inverse correlation was found for IL-12 (r=-0.611, p<0.02) but not for IL-10 (r=
      0.341, ns). These data are suggestive for a disturbed glucocorticoid regulation
      of IL-10 in CFS.

PMID- 11585639
TI  - Upregulation of the inhibitor of apoptosis proteins in activated T lymphocytes
      from patients with multiple sclerosis.
AB  - The pathogenesis of multiple sclerosis (MS) may involve failure of programmed
      cell death (apoptosis) to eliminate potentially pathogenic, autoreactive T
      lymphocytes. This failure may be caused by multiple abnormalities of the cell
      death machinery. In this study, we investigated the expression of the inhibitors
      of apoptosis (IAP) proteins, cellular IAP-1, IAP-2, and X-linked IAP (XIAP), in T
      lymphocytes from patients with active relapsing-remitting MS and appropriate
      controls. The expression of IAP proteins was significantly higher in mitogen
      stimulated intrathecal and peripheral T lymphocytes from MS patients when
      compared to corresponding expressions from inflammatory and non-inflammatory
      neurologic controls, and healthy individuals. IAP proteins were also expressed in
      resting (unstimulated) T lymphocytes predominantly from MS patients. The
      heightened expression of IAP proteins in MS patients correlated with T lymphocyte
      resistance to apoptosis, and was independent of cellular expression of the death
      receptor protein Fas. In contrast, cellular expression of the anti-apoptosis
      protein Bcl-2 was relatively similar between MS patients and the control groups.
      These findings suggest that over-expression of IAP proteins in mitogen-stimulated
      T lymphocytes is a feature of multiple sclerosis.

PMID- 11585640
TI  - Heightened expression of survivin in activated T lymphocytes from patients with
      multiple sclerosis.
AB  - The perpetuation of the inflammatory process in multiple sclerosis (MS) may arise
      from the failure to eliminate potentially pathogenic autoreactive lymphocytes by
      programmed cell death (apoptosis). Such impairment may be caused by multiple
      abnormalities of apoptosis regulatory proteins. In this study, we investigated
      the expression of survivin, a recently described cell cycle-regulated
      antiapoptosis protein, in lymphocytes from patients with active relapsing
      remitting MS and appropriate controls. Survivin reactivity was detected in
      intrathecal lymphocytes from some MS patients, but not in resting peripheral
      lymphocytes. However, mitogen stimulation of resting lymphocytes induced survivin
      expression, which was significantly higher in stimulated intrathecal and
      peripheral T lymphocytes from MS patients when compared to controls. In contrast,
      cellular expression of the antiapoptosis protein Bcl-2 was relatively similar
      between MS patients and the control groups. Moreover, heightened survivin
      expression in MS patients correlated with T lymphocyte resistance to apoptosis,
      and was independent of cellular expression of the death receptor Fas. These
      findings suggest that upregulation of the antiapoptotic protein survivin in
      mitogen-stimulated T lymphocytes is a feature of multiple sclerosis.

PMID- 11585641
TI  - Inflammatory gene transcription in human astrocytes exposed to hypoxia: roles of
      the nuclear factor-kappaB and autocrine stimulation.
AB  - Mechanisms of hypoxia-induced activation of nuclear factor-kappaB (NF-kappaB) and
      inflammatory genes were investigated in fetal human astrocytes in culture.
      Astrocytes were subjected to interleukin-1beta (IL-1beta; 50-100 u/ml; 4-24 h),
      or to a 4-h hypoxia (<2% O2) followed by a 4-24-h reoxygenation. NF-kappaB
      binding and transcriptional activity increased up to 10-fold in astrocytes
      exposed to IL-1beta, and up to 3-fold in astrocytes subjected to hypoxia followed
      by reoxygenation. Both IL-1beta- mRNAs and proteins hypoxia-induced NF-kappaB
      activation were blocked by the proteasome inhibitor, MG-132. MG-132 inhibited IL
      1beta-induced up-regulation of IL-1beta and IL-8 mRNA and protein but increased
      hypoxia-stimulated expression/release of IL-1beta and IL-8. IL-1 receptor
      antagonist (IL-1Ra) blocked both hypoxic astrocyte-conditioned media-induced NF
      kappaB activation and the expression/release of IL-1beta and IL-8. Astrocytes
      subjected to hypoxia in the presence of IL-1Ra failed to activate NF-kappaB, but
      expressed elevated levels of IL-1beta and IL-8. The data suggest that
      hypoxia/reoxygenation-induced up-regulation of IL-1beta and IL-8 in human
      astrocytes has two components, a NF-kappaB independent up-regulation during
      hypoxia, followed by amplification through autocrine IL-1beta-induced NF-kappaB
      activation during reoxygenation.

PMID- 11585642
TI  - Myocytes respond in vivo to an antibody reactive with the acetylcholine receptor
      by upregulating interleukin-15: an interferon-gamma activator with the potential
      to influence the severity and course of experimental myasthenia gravis.
AB  - The monoclonal antibody, mAb35, which binds the main immunogenic region of the
      post-junctional muscle receptor for acetylcholine (AChR), results in contractile
      dysfunction and symptoms of experimental myasthenia gravis (EAMG). As described
      below, exposure to mAb35 also results in the production by muscle of increased
      levels of the interferon-gamma (IFN-gamma)-activating cytokine, interleukin-15.
      This effect is accompanied by the increased trafficking of leukocytes through
      muscle, some that produce IFN-gamma. These observations may be relevant to the
      induction of disease symptoms since numerous reports from other investigators
      indicate that IFN-gamma may play a pivotal role in this disease process.

PMID- 11585643
TI  - Gene-targeting in Drosophila validated.

PMID- 11585644
TI  - Causes of the phenotype-genotype dissociation in DiGeorge syndrome: clues from
      mouse models.

PMID- 11585645
TI  - How many nuclear hormone receptors are there in the human genome?
AB  - The sequence of the human genome now allows the definition of the complete set of
      genes for specific protein families in humans. Because of their involvement in
      many physiological and pathological processes, the nuclear hormone receptors are
      a superfamily of crucial medical significance. Although 48 human nuclear receptor
      genes were identified previously, their total number is unclear from early human
      genome reports. Here, we report the identification and classification of all
      nuclear receptor genes in the human genome, and we discuss corresponding
      transcriptome and proteome diversity.

PMID- 11585646
TI  - Does the evolutionary history of aminoacyl-tRNA synthetases explain the loss of
      mitochondrial tRNA genes?
AB  - The importation of cytosolic tRNAs is required for protein synthesis in the
      mitochondria of the wide variety of eukaryotes that lack a complete set of
      mitochondrial tRNA genes. The evolutionary history of the process, however, is
      still enigmatic. The analysis presented here suggests that the loss of distinct
      mitochondrial tRNA genes was not random and that it might be explained by the
      differential capabilities of mitochondrial aminoacyl-tRNA synthetases to charge
      imported eukaryotic-type tRNAs with amino acid.

PMID- 11585662
TI  - Ever since Knudson.
AB  - Many publications have documented loss of heterozygosity (LOH) on many different
      chromosomes in a wide variety of tumours, implicating the existence of multiple
      tumour suppressor genes (TSGs). Knudson's two-hit hypothesis predicts that these
      LOH events are the second step in the inactivation of both alleles of a TSG.
      However, to date the number of TSGs identified that are inactivated mainly at the
      somatic level in cancers and are not inherited has remained disappointingly
      small. Here we postulate that the accurate mapping of LOH events in a series of
      tumours to define a common LOH region is greatly confounded by deficient LOH
      detection, genetic instability and intertumour heterogeneity. Finding the TSGs in
      chromosomal regions of frequent LOH might require 'brute-force' genomic
      approaches.

PMID- 11585663
TI  - Divide and conquer: pattern formation in Drosophila embryonic epidermis.
AB  - The pattern of differentiated cell types within tissues and organs is often
      established by organizers, the localized sources of secreted ligands. Although
      the mechanisms underlying organizer function have been extensively studied, only
      in a few cases is it clear how an organizer ultimately controls each individual
      cell's fate across a field of progenitor cells. One of these cases involves the
      establishment of a precise pattern of cell differentiation across the embryonic
      epidermis in Drosophila. Here, we review several recent reports that help to
      elucidate the regulatory principles used to control this pattern. Because
      organizers are conserved, the same fundamental principles might operate in other
      organizers.

PMID- 11585665
TI  - Deletional bias and the evolution of bacterial genomes.
AB  - Although bacteria increase their DNA content through horizontal transfer and gene
      duplication, their genomes remain small and, in particular, lack nonfunctional
      sequences. This pattern is most readily explained by a pervasive bias towards
      higher numbers of deletions than insertions. When selection is not strong enough
      to maintain them, genes are lost in large deletions or inactivated and
      subsequently eroded. Gene inactivation and loss are particularly apparent in
      obligate parasites and symbionts, in which dramatic reductions in genome size can
      result not from selection to lose DNA, but from decreased selection to maintain
      gene functionality. Here we discuss the evidence showing that deletional bias is
      a major force that shapes bacterial genomes.

PMID- 11585664
TI  - The RET receptor: function in development and dysfunction in congenital
      malformation.
AB  - Germline mutations in the RET proto-oncogene are responsible for two unrelated
      neural crest disorders: Hirschsprung disease, a congenital absence of the enteric
      nervous system in the hindgut, and multiple endocrine neoplasia type 2, a
      dominantly inherited cancer syndrome. Moreover, somatic rearrangements of RET are
      causally involved in the genesis of papillary thyroid carcinoma. The receptor
      tyrosine kinase encoded by the RET gene acts as the subunit of a multimolecular
      complex that binds four distinct ligands and activates a signalling network
      crucial for neural and kidney development. Over the past few years, a clearer
      picture of the mode of RET activation and of its multifaceted role during
      development has started to emerge. These findings, which provide new clues to the
      molecular mechanisms underlying RET signalling dysfunction in Hirschsprung
      disease, are summarized in this review.

PMID- 11585667
TI  - Developmental genetics of gametophytic apomixis.
AB  - Some higher plants reproduce asexually by apomixis, a natural way of cloning
      through seeds. Apomictic plants produce progeny that are an exact genetic replica
      of the mother plant. The replication is achieved through changes in the female
      reproductive pathway such that female gametes develop without meiosis and embryos
      develop without fertilization. Although apomixis is a complex developmental
      process, genetic evidence suggests that it might be inherited as a simple
      mendelian trait - a paradox that could be explained by recent data derived from
      apomictic species and model sexual organisms. The data suggest that apomixis
      might rely more on a global deregulation of sexual reproductive development than
      on truly new functions, and molecular mechanisms for such a global deregulation
      can be proposed. This new understanding has direct consequences for the
      engineering of apomixis in sexual crop species, an application that could have an
      immense impact on agriculture.

PMID- 11585668
TI  - Mouse models of human diseases: what can we learn?
AB  - Heightened interest in disease models is one very clear outcome of the Human
      Genome Project. Teams are now racing to identify the genes that cause disease,
      enabling the study of their function in mouse models for subsequent research into
      prevention and therapy. The simultaneous evolution of gene knockout and mutation
      technology in mice has provided the prime opportunity to facilitate the
      elucidation of genetic etiology of inherited disorders in humans. In this online
      supplement, leading scientists review such work by disease type, from Alzheimer's
      disease to DiGeorge syndrome. This valuable collection provides readers with
      timely, comprehensive reviews of mouse knockout and mutation research, including
      focus on single candidate gene knockouts to complex transgenics. We hope that you
      will find this supplement enjoyable and informative reading.

PMID- 11585669
TI  - Of mice, men and motor neurons.
AB  - The use of mouse models has been of particular importance in studying the
      pathogenesis of amyotrophic lateral sclerosis. Here, we describe both transgenic
      and classical mutants for which the genetic lesion is known. We draw attention,
      wherever possible, to pathological factors common to multiple models.

PMID- 11585670
TI  - Transgenic mouse models of Alzheimer's disease.
AB  - Recent advances in the understanding of the genetic basis of Alzheimer's disease
      have enabled the production of transgenic mouse models of the disease. Utilizing
      both cDNA- and genomic-based approaches, these mouse models for Alzheimer's
      disease have already provided valuable insights into the pathogenesis of the
      disease and potential therapeutic interventions.

PMID- 11585671
TI  - Developing models of DiGeorge syndrome.
AB  - DiGeorge syndrome is a common congenital disorder characterized by neural-crest
      related developmental defects. Mouse models of DiGeorge syndrome have been
      created that recapitulate defects seen in human patients. Here, the genetic
      pathways regulating cardiac neural crest development are reviewed and the
      evidence implicating TBX1 and other genes on chromosome 22q11 in the pathogenesis
      of DiGeorge syndrome is summarized.

PMID- 11585672
TI  - BRCA1-associated tumorigenesis: what have we learned from knockout mice?
AB  - A series of allelic mutations in the tumor suppressor Brca1 have been created to
      study mechanisms underlying BRCA1-associated tumorigenesis. Brca1 is essential in
      maintaining genome integrity through its involvement in DNA damage repair, G(2)-M
      cell-cycle checkpoint and centrosome duplication. The loss of Brca1 is not
      sufficient for malignant transformation, rather, it triggers multiple genetic
      alterations, including the inactivation of p53 and activation of a number of
      oncogenes, that ultimately result in mammary tumorigenesis.

PMID- 11585673
TI  - Molecular genetic analysis of diabetes in mice.
AB  - Transgenic and 'knockout' models are increasingly used to study the role of the
      immune system, insulin signaling and beta-cell gene transcription in diabetes.
      Mice and humans have similar genetics, developmental biology and physiology. In
      interpreting these models, however, one needs to be mindful of some differences
      that exist between mice and humans.

PMID- 11585674
TI  - Mouse models of cystic fibrosis.
AB  - The development of mouse models for cystic fibrosis has provided the opportunity
      to dissect disease pathogenesis, correlate genotype and phenotype, study disease
      modifying genes and develop novel therapeutics. This review discusses the
      successes and the challenges encountered in characterizing and optimizing these
      models.

PMID- 11585675
TI  - Mouse models of abnormal skeletal development and homeostasis.
AB  - Studies of a number of mouse mutations with skeletal defects have contributed
      significantly to the understanding of bone development and homeostasis. In many
      cases, such mutants are also genetic models of disorders in humans, characterized
      by reduced bone mass (osteoporosis), increased bone mass (osteopetrosis), or
      abnormalities in endochondral ossification (chondrodysplasias).

PMID- 11585676
TI  - Beta-adrenergic axis and heart disease.
AB  - Beta-adrenergic receptors (beta-ARs) belong to a large family of G-protein
      coupled receptors (GPCRs) that form the interface between the sympathetic nervous
      system and the cardiovascular system. The beta-AR signal system is one of the
      most powerful regulators of cardiac function, mediated by the effects of the
      sympathetic transmitters epinephrine and norepinephrine. In a number of cardiac
      diseases, however, the biology of beta-AR signaling pathways is altered
      dramatically. Here we discuss the role of beta-AR signaling in the normal and
      abnormal heart and how the use of genetically engineered mouse models has helped
      in our understanding of the pathophysiology of cardiac disease.

PMID- 11585677
TI  - Knockout models resulting in the development of obesity.
AB  - Our understanding of body weight regulation has been greatly advanced by the
      characterization of previously existing mutations in mice that cause obesity.
      Subsequent analysis of a number of mouse knockout models has greatly expanded the
      number of genes known to influence adiposity by affecting metabolic rate,
      physical activity, and/or appetite.

PMID- 11585678
TI  - How circulating cytokines trigger the neural circuits that control the
      hypothalamic-pituitary-adrenal axis.
AB  - It is now no secret that the brain plays a crucial role in organizing, adapting
      and restraining the systemic inflammatory response via a complex cascade of
      mechanisms involving proteins of the innate immune system, molecules of the
      proinflammatory signal transduction pathways, prostaglandins (PGs) and specific
      populations of neurons. These neuronal circuits, in particular those controlling
      autonomic functions, are all together involved in engaging the physiological
      responses that may help eliminating the foreign material and adjust the
      inflammatory events to prevent detrimental consequences. For instance, elevation
      in plasma glucocorticoid levels is one of the most powerful endogenous and well
      controlled feedback on the pro-inflammatory signal transduction machinery taking
      place across the organisms. The main Center that controls this neuroendocrine
      system is the paraventricular nucleus of the hypothalamus (PVN) that receives
      neuronal projections from numerous hypothalamic and extra-hypothalamic nuclei and
      areas. There is now compelling evidence that molecules produced by cells of the
      blood-brain barrier (BBB) may bind to their cognate receptors expressed at the
      surface of neurons that are responsible to trigger the hypothalamic-pituitary
      adrenal (HPA) axis. This review presents the new molecular insights regarding the
      pro-inflammatory signal transduction pathways that occur in these cells and how
      they are related to the neuroendocrine circuits mediating the increase in plasma
      glucocorticoid levels during systemic and localized immunogenic insults.

PMID- 11585679
TI  - Lack of evidence for opioid tolerance or dependence in rhesus monkeys following
      high-dose anabolic-androgenic steroid administration.
AB  - Prolonged use of high-dose anabolic-androgenic steroids (AAS) may induce a
      dependence syndrome, and emerging evidence suggests that AAS effects on
      endogenous opioid systems may contribute to AAS abuse. The present study tested
      the hypothesis that high dose AAS treatment enhances endogenous opioid activity
      in rhesus monkeys as revealed by 1) tolerance to the antinociceptive effects of
      the mu opioid agonist morphine and 2) physical dependence as indicated by
      evidence of opioid withdrawal following administration of the opioid antagonist
      naloxone. Three rhesus monkeys were treated for 14 days with 3.2 mg/kg/day
      testosterone propionate, and the effects of morphine (0.32-10 mg/kg) and naloxone
      (0.01-0.32 mg/kg) were examined both before and during treatment. Morphine
      antinociception was evaluated using a warm-water tail-withdrawal procedure, and
      naloxone-precipitated withdrawal was evaluated using checked behavioral signs and
      measures of ventilatory rate. Chronic testosterone administration for 14 days
      produced a 100-fold increase in mean plasma testosterone levels. However,
      testosterone treatment did not significantly alter the antinociceptive effects of
      morphine, and naloxone did not precipitate signs of opioid withdrawal either
      before or during testosterone treatment. These data do not support the hypothesis
      that high-dose AAS treatment enhances endogenous opioid activity in rhesus
      monkeys in a way that produces opioid tolerance or dependence.

PMID- 11585680
TI  - Association between immune activation and early depressive symptoms in cancer
      patients treated with interleukin-2-based therapy.
AB  - The relationship between immune activation and the development of early
      depressive symptoms were studied in 33 cancer patients undergoing cytokine
      therapy. Patients were treated either with subcutaneous IL-2 administered alone
      (n=13) or in association with IFN-alpha (n=5), or with IFN-alpha alone
      administered subcutaneously at low doses (n=5) or intravenously at high doses
      (n=10). The intensity of depressive symptoms was assessed during a clinical
      interview carried out before the start of cytokine therapy and five days later
      using the Montgomery and Asberg Depression Rating Scale (MADRS). On the same
      days, blood samples were collected for each patient to measure serum
      concentrations of cytokines (IL-6, IL-10, IL-1ra) and cytokine-receptors (sIL-2R,
      LIF-R). Results showed that patients treated with IL-2 or IL-2+IFN-alpha
      displayed concomitant mood symptoms and increased serum cytokine levels during
      treatment. In these patients, the intensity of depressive symptoms at endpoint
      was positively correlated with the increases measured in serum levels of IL-10
      between baseline and endpoint. IL-10 is an anti-inflammatory cytokine that is
      produced in response to the production of pro-inflammatory cytokines, and thereby
      reflects an inflammatory response. These results support the hypothesis of close
      relationship between depressive symptoms and the activation of the cytokine
      network.

PMID- 11585681
TI  - Enhanced antifungal activity of ketoconazole by Euphorbia characias latex against
      Candida albicans.
AB  - The in vitro suseptibility of Candida albicans to ketoconazole and Euphorbia
      characias latex alone or in combination was tested using the macrobroth dilution
      method. The MIC 80% of crude latex and ketoconazole are respectively 159 microg
      protein/ml and 0.3901 microg/ml. This method permits us to determine an affinity
      constant K(aff) for crude latex (0.015 microg(-1) protein ml) and ketoconazole
      (23.828 microg(-1) ml). The utilization of a mixture of latex at several
      concentrations (7.8-15.62-31.25-62.5 and 125 microg protein/ml) and ketoconazole
      indicates a synergistic effect between latex and ketoconazole. For latex
      concentrations of 31.25 and 62.5 microg protein/ml the MIC 80% of ketoconazole
      were inferior (0.194 and 0.183 microg/ml respectively) to that obtained with
      ketoconazole alone (0.390 microg/ml). A synergistic effect is therefore obtained
      between ketoconazole on the one hand and two concentrations of Euphorbia
      characias latex.

PMID- 11585683
TI  - Crinum species in traditional and modern medicine.
AB  - Crinums are large, showy plants with umbels of lily-like flowers. They are found
      in tropical and subtropical regions throughout the world, where, for centuries,
      they have been used traditionally to cure ailments and diseases. Sometimes they
      are prescribed for the same medicinal purpose. This would suggest that they
      contain a common ingredient. Phytochemical analysis has recently yielded a vast
      array of compounds, including more than 150 different alkaloids. These are of the
      Amaryllidaceae type, whose most noted effects are: analgesic, anticholinergic,
      antitumour and antiviral. Even though much has been reported on the medicinal
      properties of Crinum, only an estimated 20% of the species worldwide are
      represented in these analyses, as reviewed in this paper.

PMID- 11585682
TI  - Anti-inflammatory, analgesic and anti-lymphocytic activities of the aqueous
      extract of Crinum giganteum.
AB  - The anti-inflammatory, anti-lymphocytic and analgesic properties of Crinum
      giganteum, a popular herb used for the management of asthma and other respiratory
      disorders was investigated in rats and mice. The extract dose-dependently
      produced significant (P<0.05) inhibition of formalin induced pain in rats. It
      also demonstrated significant (P<0.01) inhibition of abdominal constriction
      induced with 0.75% v/v acetic acid in mice. On the cotton pellet induced
      granulomatous tissue formation in rats, the extract significantly (P<0.05)
      decreased the weight. However, no significant inhibition was observed in the egg
      albumin-induced inflammation in rats. Oral administration of this extract in rats
      for 14 days significantly affected (P<0.05) the total leukocyte count and the
      overall percentage lymphocytes. The intraperitoneal and per oral LD(50) were
      627+/-5.8mg/kg and 1486+/-18.9 mg/kg in mice and 520+/-10.2mg/kg and 1023+/-4.3
      mg/kg in rats, respectively. Preliminary phytochemical analysis of the extract
      indicates the presence of tannins. These results therefore indicate that C.
      giganteum bulb contains biologically active principles, which have potentials for
      the treatment of inflammatory processes.

PMID- 11585684
TI  - Active constituents isolated from Psoralea glandulosa L. with antiinflammatory
      and antipyretic activities.
AB  - The antiinflammatory and antipyretic activities of the petroleum ether extract
      (PEE), dichloromethane extract (DME) and methanol extract (ME1) of the aerial
      part of Psoralea glandulosa L. (Papilionaceae) were studied. The bioactivity
      guided fractionation of the active extracts yielded the isolation of bakuchiol
      (Bk) from the petroleum ether as the active compound, cyclobakuchiols A and B
      (Cbk), and angelicin (Ang) from DME.

PMID- 11585685
TI  - Neuropharmacological effect of the aqueous extract of Sphaeranthus senegalensis
      in mice.
AB  - Effects of the aqueous extract of Sphaeranthus senegalensis Vaill. (Family:
      Compositae) were studied on spontaneous motor activity, exploratory behaviour,
      rota-rod performance and pentobarbital sleeping time in mice. Preliminary
      phytochemical evaluation and acute toxicity (LD(50)) values were also studied.
      The extract (50 and 100 mg/kg p.o.) produced reduction in spontaneous motor
      activity, exploratory behaviour and motor coordination and prolonged
      pentobarbital sleeping time. Glycosides, saponins and tannins were shown to be
      present in the extract. The i.p. LD(50) in mice was 2735.61 and 5000 mg/kg
      orally. The results suggest that the aqueous extract of S. senegalensis contains
      some active principles, which may be sedative in nature.

PMID- 11585686
TI  - In vitro studies on the immunomodulatory effects of extracts of Osbeckia aspera.
AB  - Ayruvedic medical practitioners in Sri Lanka use aqueous extracts of the mature
      leaves of Osbeckia aspera to treat liver disease. The extract has been shown to
      have hepatoprotective effects in vitro and in vivo, and to have inhibitory
      effects on the complement system and on in vitro phagocytosis by
      polymorphonuclear cells. The aim of this study was to investigate the effect of
      an aqueous extract of Osbeckia on lymphocyte proliferation stimulated by mitogens
      and antigen. In control peripheral blood mononuclear cells (PBMC), high
      concentrations of the Osbeckia extract were inhibitory to proliferation
      stimulated by phytohaemagglutinin (PHA) and tuberculin purified protein
      derivative (PPD). On stimulation by phorbol myristate acetate and ionomycin
      (PMA+I) the extract showed stimulation of proliferation at low concentrations
      (<10 microg/ml) with inhibition at higher concentrations. A similar inhibitory
      pattern on mitogen/antigen stimulation was seen with PBMC from patients with
      chronic hepatitis C virus (HCV) infection. These results suggest that the
      inhibitory agent(s) in the aqueous extract of Osbeckia may have an effect on
      antigen-presenting cell function. The combined hepatoprotective and
      immunosuppressive effects of the extract are more likely to be beneficial in
      acute hepatitis rather than chronic hepatitis viral infection.

PMID- 11585687
TI  - Isolation of a bronchodilator flavonoid from the Thai medicinal plant
      Clerodendrum petasites.
AB  - The ethanolic extract of Clerodendrum petasites was tested to evaluate the
      spasmolytic activity on isolated guinea-pig tracheal smooth muscle. The crude
      extract (2.25-9.0 mg/ml) dose-dependently caused relaxation of tracheal smooth
      muscle which was contracted by exposure to histamine. A bioassay-guided
      fractionation of the crude extract was performed by means of partitioning and
      centrifugal partition chromatography. Finally the active principle was isolated
      and identified as the flavonoid hispidulin (EC(50): (3.0+/-0.8)x10(-5) M). These
      results suggest that hispidulin may be beneficial in the treatment of asthma.

PMID- 11585688
TI  - The effect of Senecio latifolius a plant used as a South African traditional
      medicine, on a human hepatoma cell line.
AB  - A number of traditional remedies used in South Africa contain pyrrolizidine
      alkaloids, some of which are hepatotoxic. We investigated the effect on human HuH
      7 cells of Senecio latifolius DC., a plant that is a component of some
      traditional remedies and which is known to contain toxic pyrrolizidine alkaloids.
      Cells were also treated with extracts of a standard pyrrolizidine, retrorsine.
      The changes in the gross morphology of the cells were studied using light
      microscopy after haematoxylin and eosin staining. The cytoskeleton was
      investigated using fluorescence-labelled anti-beta-tubulin antibody and the
      nuclear organisation was studied using fluorescence-labelled antinuclear
      antibodies. The plant extracts gave rise to dose-dependent gross morphological
      changes. At high doses, we observed necrosis and at lower doses, destruction of
      the cytoskeleton, nuclear fragmentation and apoptosis. Doses of less than the
      equivalent of 330 ng/ml retrorsine led to multinucleated cells with failure in
      spindle formation and clumping of nuclear chromatin. This latter finding suggests
      that chronic low-dose treatment with such traditional remedies could give rise to
      teratogenic and/or carcinogenic effects.

PMID- 11585689
TI  - Anti-amoebic activity of plant compounds from Virgilia oroboides and Chlorophora
      excelsa.
AB  - The anti-amoebic activity of four plant extracts: maackiain and formononetin from
      Virgilia oroboides and chlorophorin and Iroko from Chlorophora excelsa, were
      evaluated. Anti-protozoal tests conducted on trophozoites of Entamoeba
      histolytica established that all four compounds had an affect on the trophozoites
      to some degree. Chlorophorin showed the highest anti-protozoal activity with an
      MIC of 0.25 microg/ml followed by maackiain and Iroko with MICs of 1 microg/ml.
      Chlorophorin and Iroko induced the release of acid phosphatase. Chlorophorin
      reduced alpha amylase levels by 89%. Formononetin and maackiain had a minimal
      effect on the enzyme levels. Ultrastructural changes occurred in trophozoites
      treated with plant compounds. The degree of destruction of the trophozoites
      increased with an increase in compound concentration. Trophozoite destruction was
      initiated by the disintegration of the nucleus and culminated with the rupture of
      the cytoplasmic membrane. Maackiain was the only compound that showed some level
      of mutagenicity. Formononetin and Iroko were very slightly mutagenic, while
      chlorophorin was non-mutagenic. In addition, none of the compounds tested showed
      cytopathic effects on any of the cell lines tested. Chlorophorin and Iroko
      exhibit the potential to be exploited as natural multi-functional safe control
      agents in the treatment of bacterial, fungal and protozoal infections.

PMID- 11585690
TI  - Antihyperglycemic activity of Momordica cymbalaria in alloxan diabetic rats.
AB  - Aqueous, ethanolic and hexane fractions of Momordica cymbalaria fruits were
      prepared and given individually at different doses to different batches of rats
      (both normal and alloxan diabetic rats) after an overnight fast. The blood
      glucose levels were measured at 0, 1, 3, 5 and 7 h after the treatment. The
      aqueous extract of Momordica cymbalaria at a dosage of 0.5 g/kg b.w. is showing
      maximal blood glucose lowering effect in diabetic rats. The same dosage did not
      produce any hypoglycemic activity in normal rats. The antihyperglycemic activity
      of Momordica cymbalaria fruit was compared with the treatment of Glibenclamide,
      an oral hypoglycemic agent.

PMID- 11585691
TI  - Anticonvulsant activities of ethanolic extract and aqueous fraction isolated from
      Delphinium denudatum.
AB  - Dried roots of Delphinium denudatum Wall. are a popular folk remedy for the
      treatment of epilepsy in the traditional Unani system of medicine in the sub
      continent. We carried out anticonvulsant screening of the ethanolic extract (EE)
      and aqueous fraction (AF) of this plant utilising the maximal electroshock (MEST)
      and subcutaneous pentylenetetrazole (scPTZ), bicuculline (scBIC), picrotoxin
      (scPTX) and strychnine (scSTN) tests for anticonvulsant activity. EE had weak
      dose-dependent anticonvulsant effects on seizures induced by PTZ and BIC. AF
      exhibited dose-dependent activity against hind limb tonic extension phase (HLTE)
      of MEST and comparatively stronger anticonvulsant activity against seizures
      induced by PTZ and BIC. The results suggest the presence of potent anticonvulsant
      compounds in AF of D. denudatum and deserve further investigation for isolation
      of active compounds and elucidation of the mechanism of anticonvulsant action.

PMID- 11585692
TI  - In vitro antifilarial effects of three plant species against adult worms of
      subperiodic Brugia malayi.
AB  - Five aqueous extracts from three plant species, i.e., dried husks (HX), dried
      seeds (SX) and dried leaves (LX) of Xylocarpus granatum (Meliaceae), dried stems
      (ST) of Tinospora crispa (Menispermaceae) and dried leaves (LA) of Andrographis
      paniculata (Acanthaceae) were tested in vitro against adult worms of subperiodic
      Brugia malayi. The relative movability (RM) value of the adult worms over the 24
      h observation period was used as a measure of the antifilarial activity of the
      aqueous extracts. SX extract of X. granatum demonstrated the strongest activity,
      followed by the LA extract of A. paniculata, ST extract of T. crispa, HX extract
      and LX extract of X. granatum.

PMID- 11585693
TI  - Immunomodulatory activity of Punica granatum in rabbits--a preliminary study.
AB  - Punica granatum L. (Punicaceae) fruit rind powder (PGFRP) at the dose of 100
      mg/kg orally as aqueous suspension was found to stimulate the cell-mediated and
      humoral components of the immune system in rabbits. PGFRP elicited an increase in
      antibody titer to typhoid-H antigen. It also enhanced the inhibition of leucocyte
      migration in Leucocyte Migration Inhibition test and induration of skin in
      delayed hypersensitivity test with Purified Protein Derivative (PPD) confirming
      its stimulatory effect on cell-mediated immune response.

PMID- 11585694
TI  - The insulinotropic activity of a Nepalese medicinal plant Biophytum sensitivum:
      preliminary experimental study.
AB  - The effect of the leaf extract of Biophytum sensitivum, an annual herb used in
      traditional Nepalese folk medicine for the treatment of hyperglycemic patients,
      was studied on glucose homeostasis in rabbits. In the first set of experiments,
      an acute effect of the extract on fasting plasma glucose (fpg) levels and serum
      insulin response was examined in non-diabetic and alloxan-diabetic rabbits.
      Initial dose-response studies showed that a dose of 200 mg/kg body weight (b.w.)
      was optimum for hypoglycemia. A single administration of this dose to 16-h fasted
      non-diabetic rabbits brought about a 16.1% fall in fpg at the end of 1 and 2 h,
      and the hypoglycemic effect persisted at the end of 6 h (13.8% fall). Serum
      insulin levels showed a significant rise in the treated animals, which suggested
      a pancreatic mode of action (i.e. insulinotropic effect) of B. sensitivum. The
      study of an acute effect of the extract in alloxan-diabetic rabbits, however,
      showed that it failed to produce such hypoglycemic or serum insulin response. In
      another set of experiments, administration of the above dose of the leaf extract
      attenuated the plasma glucose response to oral administration of 3 g/kg b.w.
      glucose load. The serum insulin levels in the treated animals showed a rise at
      the end of 2 (13.7% rise) and 6 h (12.6% rise). Taken together, these
      observations suggest that the hypoglycemic response of B. sensitivum may be
      mediated through stimulating the synthesis/release of insulin from the beta cells
      of Langerhans.

PMID- 11585695
TI  - Protective role of Delphinium denudatum (Jadwar) against morphine induced
      tolerance and dependence in mice.
AB  - Chronic treatment with Delphinium denudatum (Dd) (Jadwar) (family: Ranunculaceae,
      200-1600 mg/kg) suppressed morphine withdrawal jumps in a dose-dependent manner,
      a sign of the development of dependence to opiate as assessed by naloxone (2
      mg/kg) precipitation withdrawal on day 10 of testing in mice. Repeated
      administration of Dd (200-1600 mg/kg) for 9 days attenuated the development of
      tolerance to the analgesic effect of morphine (10 mg/kg), also produces
      significant change in tail-flick latency from the saline pretreated group in a
      dose-dependent manner.

PMID- 11585696
TI  - Clinical trials of ayurvedic formulations in the treatment of acne vulgaris.
AB  - Oral and externally used dermatological preparation for acne vulgaris employing
      herbal extracts have been developed and standardized, the herbal extracts used
      here were of the plants described in ayurvedic treatise like Bhavprakasha
      Nighantu and Charak Samhita. The efficacy of the treatment using the oral
      formulation with or without external preparation has been assessed through
      conduct of Phase II clinical trials in 53 patients for 4 weeks in a randomized,
      double-blind, placebo-controlled fashion and following Good Clinical Practices
      guidelines. The results were statistically analyzed and indicated that
      combination of use of internal and external preparation showed better efficacy as
      compared to the use of oral formulation alone.

PMID- 11585697
TI  - Antimicrobial activity of plants used in traditional medicine of San Juan
      province, Argentine.
AB  - Eighteen extracts from Acaena magellanica, Baccharis grisebachii, Ephedra breana,
      Oxalis erythrorhiza, Pachylaena atriplicifolia and Satureja parvifolia were
      assessed for antimicrobial activity against bacteria and fungi with the agar
      dilution method. The hexane (H) and dichloromethane (DCM) extracts of B.
      grisebachii and O. erythrorhiza showed the broadest spectrum of action against
      fungi, inhibiting all of the tested dermatophytes with MICs ranging from < or =25
      to < or =1000 microg/ml. Trichophyton rubrum was the most susceptible species and
      Cryptococcus neoformans was inhibited only by the DCM extract of B. grisebachii
      with MIC of 600 microg/ml. Regarding the antibacterial activity, H and DCM
      extracts of B. grisebachii as well as the DCM of O. erythrorhiza, were active on
      methicillin-resistant and methicillin-sensitive Staphylococcus aureus with MIC
      from < or =125 to < or =500 microg/ml. The DCM extract of B. grisebacchii was
      more active against methicillin-resistant than methicillin-sensitive strains.

PMID- 11585698
TI  - The ovine somatostatin receptor subtype 1 (osst1): partial cloning and tissue
      distribution.
AB  - The sheep is a valuable model to study GH neuroregulation since its GH secretion
      pattern is close to that in human. Somatostatin receptor subtype 1 (sst1) appears
      to be important in central regulation of GH but ovine sst1 (osst1) has not yet
      been cloned. We report here the cloning of the major part of sst1 in that
      species. Using human primers from transmembrane domain 2 and 7, we amplified from
      sheep tissue by RT-PCR a 700 bp fragment. By screening a cDNA sheep library with
      this fragment, we isolated a 1.4 kb cDNA which contained the major part of the
      coding cDNA of osst1. The partial predicted protein consists of 347 amino acids
      exhibiting a putative seven transmembrane domain topology typical of G protein
      coupled receptors. Nucleotide sequence comparisons with that of other species
      showed that osst1 displays 88% homology with human sst1, 84% with rat sst1 and
      87% with mouse sst1. Southern blot analysis of ovine cortex DNA demonstrated that
      osst1 is encoded by a single gene. Northern blot studies evidenced a 3.9 kb
      transcript highly expressed in the cortex and the hippocampus. This transcript
      was also present in hypothalamus, striatum, cerebellum, olfactory bulb, spinal
      cord, brain stem, the lung, kidney, liver, adrenal glands and at a low level in
      the pituitary gland. No signal was noticeable in the pineal gland. The sequence
      homology, the tissue distribution, the length of the transcript link this cDNA to
      the somatostatin receptor family and particularly to sst1.

PMID- 11585699
TI  - Maternal leptin is elevated during pregnancy in sheep.
AB  - Maternal plasma leptin is elevated during pregnancy in several species, but it is
      unclear to what extent this elevation reflects changes in adiposity or energy
      balance. Therefore, Karakul ewes (n = 8) were fed to minimize changes in maternal
      energy status over the pregnancy-lactation cycle. They were studied 20-40 d
      before breeding and during mid pregnancy (d 50-60 post coitus [PC]), late
      pregnancy (d 125-135 PC) and early lactation (d 15-22 post partum). Consistent
      with the maintenance of near energy equilibrium in nongravid maternal tissues,
      maternal body weight was increased only during late pregnancy when the weight of
      the conceptus became significant and plasma concentrations of insulin, NEFA and
      glucose did not vary with physiological state. In contrast, maternal plasma
      leptin concentration rose from 5.3 to 9.5 ng/mL between prebreeding and mid
      pregnancy and then declined progressively through late pregnancy and early
      lactation. Leptin gene expression increased 2.3 fold in maternal white adipose
      tissue (WAT) from prebreeding to mid pregnancy and declined to prebreeding levels
      during early lactation. To determine whether tissue response to insulin was
      involved in this effect, insulin tolerance tests were performed. The maternal
      plasma glucose response declined from prebreeding to early lactation, but was not
      correlated with either plasma leptin concentration or WAT leptin mRNA abundance.
      In conclusion, pregnancy causes an increase in the synthesis of leptin in sheep.
      This stimulation does not require increases in adiposity or energy balance and is
      unrelated to the ability of insulin to promote glucose utilization.

PMID- 11585700
TI  - Dexamethasone treatment at birth enhances neonatal growth in swine.
AB  - The objective of the present study was to determine if dexamethasone (Dex; a
      potent synthetic glucocorticoid) treatment at birth would alter postnatal growth
      in neonatal pigs. Forty crossbred pigs were injected i.m. with either sterile
      saline (Cont; n = 10 males and 10 females) or Dex (1 mg/kg; n = 10 males and 10
      females) within 1 hr of birth. All pigs remained with their respective dams until
      18 d of age. Body weights were recorded weekly and on d 18. On d 17, all pigs
      were nonsurgically fitted with an indwelling jugular catheter and placed back
      with the sows. On d 18, all pigs were placed in individual pens for serial blood
      collection. Birth weights (1.53 +/-.04 kg) did not differ between birth
      treatments or sex classes (P > 0.70 and 0.89, respectively). A time by treatment
      effect was detected (P < 0.007) for body weight such that those pigs which
      received Dex at birth had the greatest body weights during the 18-d period.
      Average daily gain was increased (P < 0.017) by 12.2% in those pigs which
      received Dex at birth (.286 +/-.007) as compared to the Cont pigs (.255 +/-.01
      kg/d). Serum concentration of IGF-1 was influenced by both treatment (P < 0.0001)
      and sex class (P < 0.013). In the male pigs, Dex increased (P = 0.0041) serum
      concentration of IGF-1 by 47% as compared to Cont male pigs, whereas in the
      females, Dex increased (P < 0.011) serum concentration of IGF-1 by 34% as
      compared to Cont female pigs. Dex treatment reduced (P < 0.002) serum IGF-2 by
      12.8%. Serum concentration of IGFBP-3 was influenced by both birth treatment (P <
      0.007) and sex class (P < 0.002) such that Dex treatment increased serum IGFBP-3,
      and higher concentrations of IGFBP-3 were observed in boars as compared to gilts.
      These data suggest that the early neonatal period may be an opportune time to
      alter physiological factors which influence growth in swine.

PMID- 11585701
TI  - Neonatal estradiol exposure alters uterine morphology and endometrial
      transcriptional activity in prepubertal gilts.
AB  - Porcine endometrial development between birth (postnatal day = PND 0) and PND 56
      involves differentiation of glandular epithelium (GE) from luminal epithelium
      (LE) and estrogen receptor-alpha (ER) expression. Juvenile ER architecture
      evolves after birth, as stroma and nascent GE first express ER. Mature ER
      architecture is evident after PND 30, when stroma, GE and LE are ER-positive.
      When administered during discrete periods between PND 0 and 56, effects of
      estradiol-17beta valerate (EV) on the neonatal porcine uterus relate to
      endometrial ER architecture. Transient EV exposure from birth reduces embryo
      survival in pregnant adult gilts. Effects of EV, administered as juvenile
      endometrial ER architecture develops (P1, PND 0-13), or after mature ER
      architecture is established (P2, PND 42-55), were evaluated in uteri from gilts
      treated with corn oil or EV in P1 or P2 and hysterectomized on PND 100 without
      additional steroids (NSt), on PND 102 after EV on PND100-101 (EV2), or on PND 117
      after EV2 followed by progesterone on PND 102-116 (EP). Neonatal EV reduced
      uterine weight (P < 0.02), size (P < 0.01), luminal protein content (P < 0.07),
      and percent incorporation of 3H-leucine into nondialyzable endometrial products
      in vitro (P < 0.01). Group (NSt, EV2, EP) -specific treatment effects detected
      for endometrial ER, progesterone receptor, uteroferrin, and/or retinol binding
      protein mRNA levels were frequently related to period (P1,P2). Results support
      the idea that estrogen-sensitive postnatal organizational events, including those
      defined, in part, by endometrial ER architecture, are likely components of
      genetic and epigenetic programs governing uterine morphogenesis and ontogeny of
      endometrial function in the pig.

PMID- 11585702
TI  - Hormonal regulation of oxytocin-induced prostaglandin F(2alpha) secretion by the
      bovine and ovine uterus in vivo.
AB  - In long-term ovariectomized ewes and cows, endometrial oxytocin receptors rest at
      relatively high levels but oxytocin is unable to induce prostaglandin F(2alpha)
      release. A series of studies were carried out to investigate the roles of
      physiological levels of progesterone and estradiol in "activating" these
      receptors in terms of permitting oxytocin-induced prostaglandin F(2alpha)
      release. In long-term ovariectomized cows, treatment with progesterone, but not
      estradiol, resulted in the induction of responsiveness to oxytocin. This
      responsiveness appeared within 2 d of progesterone treatment, reached a maximum
      by 6 d and was maintained to Day 18. In ovariectomized ewes, while estradiol
      treatment did induce temporary responsiveness to oxytocin after 3 d of treatment,
      treatment with progesterone was required to induce sustained responsiveness that
      appeared by Day 9 of treatment and was maintained to Day 12. Measurement of
      endometrial receptors for oxytocin revealed a significant decline in oxytocin
      receptors by Day 6 of progesterone treatment when responsiveness to oxytocin was
      maximal, demonstrating that receptor concentrations were not a limiting factor.
      The most likely mechanism by which progesterone treatment induces responsiveness
      to oxytocin may be through the up regulation of post receptor signaling pathways
      and/or enzymes involved in prostaglandin synthesis.

PMID- 11585704
TI  - Free radical-induced double lesions in DNA.
AB  - This review surveys the work that has been done on free radical-induced DNA
      double lesions. Double lesions consist of two modifications of the DNA in close
      proximity. Double lesions can be generated by a single free radical-initiating
      event and the mechanism of formation often involves the participation of guanine.
      The identification of double lesions in oligomer and polymer DNA is reviewed and
      possible mechanisms of formation are outlined. The potential biological
      significance of double lesions is discussed. Double lesions induced by UV light
      are outside the scope of this review.

PMID- 11585703
TI  - Transduction pathways involved in Hypoxia-Inducible Factor-1 phosphorylation and
      activation.
AB  - Hypoxia-Inducible Factor-1 (HIF-1) is a transcription factor which is activated
      by hypoxia and involved in the adaptative response of the cell to oxygen
      deprivation. During hypoxic stress, HIF-1 triggers the overexpression of genes
      coding for glycolytic enzymes and angiogenic factors. To be active HIF-1 must be
      phosphorylated. HIF-1 is a substrate for various kinase pathways including PI-3K
      and the MAP kinases ERK and p38. Several transduction pathways have been proposed
      which act downstream of putative oxygen sensors and lead to the activation of
      these kinases. In this review, we summarize some of the latest advances
      describing the possible signaling pathways leading to HIF-1 phosphorylation and
      subsequent activation. The physiological relevance of these regulations is also
      discussed.

PMID- 11585705
TI  - The influence of pH on antioxidant properties and the mechanism of antioxidant
      action of hydroxyflavones.
AB  - The effect of the pH on antioxidant properties of a series of hydroxyflavones was
      investigated. The pKa of the individual hydroxyl moieties in the hydroxyflavones
      was compared to computer-calculated deprotonation energies. This resulted in a
      quantitative structure activity relationship (QSAR), which enables the estimation
      of pKa values of individual hydroxyl moieties, also in hydroxyflavones for which
      these pKa values are not available. Comparison of the pKa values to the pH
      dependent antioxidant profiles, determined by the TEAC assay, reveals that for
      various hydroxyflavones the pH-dependent behavior is related to hydroxyl moiety
      deprotonation, resulting in an increase of the antioxidant potential upon
      formation of the deprotonated forms. Comparison of these experimental results to
      computer calculated O-H bond dissociation energies (BDE) and ionization
      potentials (IP) of the nondeprotonated and the deprotonated forms of the various
      hydroxyflavones indicates that especially the parameter reflecting the ease of
      electron donation, i.e., the IP, and not the BDE, is greatly influenced by the
      deprotonation. Based on these results it is concluded that upon deprotonation the
      TEAC value increases (radical scavenging capacity increases) because electron-,
      not H*-, donation becomes easier. Taking into account that the mechanism of
      radical scavenging antioxidant activity of the neutral form of the
      hydroxyflavones is generally considered to be hydrogen atom donation, this
      implies than not only the ease of radical scavenging, but also the mechanism of
      antioxidant action changes upon hydroxyflavone deprotonation.

PMID- 11585706
TI  - Superoxide-mediated activation of cardiac fibroblasts by serum factors in
      hypomagnesemia.
AB  - Magnesium deficiency is known to produce myocardial fibrosis in different animal
      models, but the underlying mechanisms are unclear. However, circulating levels of
      pro-oxidant and mitogenic factors are reported to be elevated in a rodent model
      of acute magnesium deficiency, suggesting a role for humoral factors in the
      pathogenesis of the cardiovascular lesions. Probing the mechanism of cardiac
      fibrogenesis in magnesium deficiency, the present study furnished evidence that
      serum from magnesium-deficient rats has a more marked effect than serum from
      magnesium-sufficient rats on mitogenesis, net collagen production, and superoxide
      generation in cardiac fibroblasts from young adult rats. The enhanced mitogenic
      response was abolished by superoxide dismutase and N-acetyl cysteine, showing
      that it is mediated by superoxide anion. Further, a modest inhibitory effect of
      the neurokinin-1 receptor antagonist, spantide, suggested that factors acting via
      neurokinin-1 receptors may partly modulate cardiac fibroblast function in
      magnesium deficiency. The findings are consistent with the postulation that serum
      factors may activate cardiac fibroblasts via a superoxide-mediated mechanism and
      contribute to the fibrogenic response in the heart in magnesium deficiency.

PMID- 11585707
TI  - Proteasomal degradation of oxidatively damaged endogenous histones in K562 human
      leukemic cells.
AB  - A number of antitumor drugs act via the oxidation of nuclear material in the
      tumor cell. It is therefore important to know if tumor cells can effectively and
      precisely cope not only with oxidatively induced DNA damage, but also with
      nuclear protein oxidation. In this study, we investigated the endogenous
      degradation of oxidatively damaged histones in K562 human leukemic cells after
      oxidative challenge and demonstrated a link to the overall cellular stress
      response pathways by poly-ADP-ribose-polymerase (PARP). After an oxidative
      challenge, endogenous nuclear protein degradation, as well as histone
      degradation, was enhanced. Among the histone fractions, histone H1 revealed the
      highest degradation rate, and more than 85% of the total degraded H1 disappeared
      in the first 30 min after oxidative challenge. Short-term degradation of histones
      up to 30 min, as well as long-term degradation up to 48 h after oxidative
      challenge, was significantly reduced in the presence of the PARP inhibitor 3
      aminobenzamide, and nearly completely abrogated by the selective proteasome
      inhibitor lactacystin. Immunoprecipitation experiments indicated that the
      proteasome specifically degraded oxidized histones. Thus, we show that the
      nuclear proteosome system in tumor cells is capable of preventing the
      accumulation of oxidized proteins in this compartment and may suggest further
      treatment strategies to effectively interfere with the protein "repair" and
      replacement strategies of tumor cells.

PMID- 11585708
TI  - A real-time electrochemical technique for measurement of cellular hydrogen
      peroxide generation and consumption: evaluation in human polymorphonuclear
      leukocytes.
AB  - There has been a long-standing need for sensitive and specific techniques for
      hydrogen peroxide (H(2)O(2)) measurement. We describe the development and
      application of a highly sensitive electrochemical sensor, utilizing a membrane
      coated platinum microelectrode, suitable for real-time measurement of hydrogen
      peroxide generation and consumption in biochemical or cellular systems. This
      sensor provides high sensitivity enabling measurement of hydrogen peroxide down
      to 5-10 nM concentrations. We demonstrate that it can be used to measure the
      magnitude and time course of H(2)O(2) generation from the NADPH oxidase in
      leukocytes as well as the rate of H(2)O(2) degradation. After human
      polymorphonuclear leukocytes (PMNs) were activated by phorbol 12-myristate
      acetate, H(2)O(2) concentration increased with time and reached a peak
      concentration, from 5 to 15 microM in PMNs prepared from different individuals,
      within 3 to 8 min, then decreased slowly. The H(2)O(2) concentration in the
      solution is less than the total H(2)O(2) generation from the activated PMNs
      because a part of H(2)O(2) generated is decomposed. H(2)O(2) in solution,
      generated from the PMNs, was rapidly consumed after the activated PMNs were
      treated with 10 microM diphenylene iodonium (DPI). The rate of H(2)O(2)
      consumption was measured following the addition of exogenous H(2)O(2). The total
      production of H(2)O(2) from the activated PMNs was calculated from the measured
      H(2)O(2) concentration and the rate of H(2)O(2) consumption. This technique
      enables sensitive and continuous real-time measurement of H(2)O(2) concentration
      and total H(2)O(2) generation in cellular or enzyme systems without addition of
      any detection reagents.

PMID- 11585709
TI  - Hepatocyte growth factor protects cardiac myocytes against oxidative stress
      induced apoptosis.
AB  - Hepatocyte growth factor (HGF) has been proposed as an endogenous
      cardioprotective agent against oxidative stress. The mechanism of HGF action in
      the heart, however, has not yet been elucidated. The present study demonstrates
      that HGF protects adult cardiac myocytes against oxidative stress-induced
      apoptosis. HGF, at the concentrations which can be detected in the plasma of
      humans subsequent to myocardial infarction, effectively attenuated death of
      isolated adult rat cardiac myocytes and cultured HL-1 cardiac muscle cells
      induced by apoptosis-inducing oxidative stress stimuli such as daunorubicin,
      serum deprivation, and hydrogen peroxide. We identified expression of c-Met HGF
      receptor in adult cardiac myocytes, which can be rapidly tyrosine phosphorylated
      in response to HGF treatment. HGF also activated MEK, p44/42 MAPK, and p90RSK. To
      determine if MEK-MAPK pathway may be involved in the mechanism of HGF-mediated
      cardiac myocyte protection, effects of a specific MEK inhibitor, PD98059, were
      studied. Pretreatment of cells with PD98059 partially blocked HGF signaling for
      protection against hydrogen peroxide-induced cell death. Thus, HGF protects
      cardiac myocytes against oxidative stress, in part, via activating MEK-MAPK
      pathway.

PMID- 11585710
TI  - Oxidative stress in athletes during extreme endurance exercise.
AB  - Despite the many known health benefits of exercise, there is a body of evidence
      suggesting that endurance exercise is associated with oxidative stress. To
      determine whether extreme endurance exercise induces lipid peroxidation, 11
      athletes (3 females, 8 males) were studied during a 50 km ultramarathon (trial 1)
      and during a sedentary protocol (trial 2) 1 month later. The evening before each
      trial, with dinner, subjects consumed 75 mg each d(3)-RRR and d(6)-all rac-alpha
      tocopheryl acetates. Blood was obtained at baseline, 30 min pre-race, mid-race,
      post-race, 1 h post-race, 24 h post-race, and at corresponding times during trial
      2. All 11 subjects completed the race; average run time was 391 +/- 23 min.
      Plasma F(2)-isoprostanes increased from 75 +/- 7 pg/ml at pre-race to 131 +/- 17
      (p <.02) at post-race, then returned to baseline at 24 h post-race; F(2)
      isoprostanes were unchanged during trial 2. Deuterated alpha-tocopherol
      disappearance rates were faster (2.8 x 10(-4) +/- 0.2 x 10(-4)) during the race
      compared to the sedentary trial (2.3 x 10(-4) +/- 0.2 x 10(-4); p <.03). These
      data suggest that extreme endurance exercise results in the generation of lipid
      peroxidation with a concomitant increase in vitamin E disappearance.

PMID- 11585711
TI  - Acute regulation of glucose transport in a human megakaryocytic cell line:
      difference between growth factors and H(2)O(2).
AB  - The present study was undertaken to: (i) compare the effect of some hematopoietic
      growth factors, like interleukine-3, thrombopoietin, granulocyte-megakaryocyte
      colony-stimulating factor, stem cell factor, and reactive oxygen species such as
      H(2)O(2) on glucose uptake in a human leukemic megakaryocytic cell line, M07;
      (ii) investigate the changes in kinetic parameters of the transport activity
      induced by these stimuli; and (iii) evaluate the effect of genistein, a tyrosine
      kinase inhibitor, on the glucose uptake activation by the cited agents. The
      results are as follows: (i) exposure of M07 cells to thrombopoietin, granulocyte
      megakaryocyte colony-stimulating factor, and stem cell factor resulted in a rapid
      stimulation of glucose transport; interleukine-3-treated cells exhibited no
      increase in the rate of glucose uptake, although M07 proliferation is
      interleukine-3 dependent; a rapid glucose transport enhancement was also observed
      when M07 cells were exposed to low doses of H(2)O(2); (ii) the transport kinetic
      parameters point out that an important difference exists between the effect of
      cytokines and that of H(2)O(2): cytokines increased predominantly the affinity
      for glucose, while H(2)O(2) raised both the V(max) and K(m) values; (iii) the
      isoflavone genistein, at a very low concentration, inhibited the stem cell factor
      or H(2)O(2)-induced stimulation of hexose transport, reversing the variations of
      K(m) and V(max), but it did not affect the transport activity of granulocyte
      megakaryocyte colony-stimulating factor-treated cells; and (iv) catalase
      completely abolished the stimulatory action of H(2)O(2) on glucose transport and
      slightly prevented the effect of stem cell factor, while caffeic acid phenethyl
      ester was only able to affect the activation due to stem cell factor.

PMID- 11585712
TI  - Relapse and recurrence prevention in major depression: a critical review of
      placebo-controlled efficacy studies with special emphasis on methodological
      issues.
AB  - This article critically reviews the design and methodology of studies aimed at
      evaluating relapse and recurrence prevention in major depression. A literature
      search in MEDLINE was performed with the medical subject headings 'depression',
      'recurrence', 'relapse', 'prevention' and 'study'. This search covered the period
      from January 1990 to July 1999. Only long-term placebo-controlled studies that
      included patients with non-chronic major depression were selected. Two types of
      design could be distinguished: randomised withdrawal studies in
      responders/remitters (N = 11) and extension studies in responders without re
      randomisation (N = 3). Randomised withdrawal studies are suitable for
      demonstrating long-term efficacy for the duration of the study period. However,
      this design does not permit a clear differentiation between relapse or recurrence
      and, therefore, is not suitable to demonstrate unequivocally relapse prevention
      or recurrence prevention. Extension studies in short-term responders without
      randomisation are not even suitable to demonstrate long-term efficacy.A novel
      design is proposed that overcomes the weaknesses of designs employed thus far. In
      essence, this design calls for a long-term randomised placebo-controlled study in
      patients who are free of medication for a substantial period of time and who
      fulfil the criteria of major depression (recurrent) in sustained remission (e.g.,
      HDRS < 7) as a possible option.

PMID- 11585713
TI  - Incidence of obsessive-compulsive phenomena in the course of acute schizophrenia
      and schizoaffective disorder.
AB  - Studies examining OC phenomena in schizophrenic and schizoaffective disorders
      have shown a prevalence of such phenomena in 1 to 60% of schizophrenic or
      schizoaffective patients. In this prospective study, about 10% of 150 male
      patients suffering from acute psychotic disorders (fulfilling DSM-IV criteria for
      Schizophrenia or Schizoaffective Disorder) were found to have OC symptoms. These
      symptoms showed no correlation to the type and severity of psychosis. As only 19%
      of the patients with obsessions and compulsions during acute psychosis showed an
      obsessive-compulsive personality disorder prior to their psychotic episodes, it
      may be concluded that there is no clear linkage between intrapsychotic OC
      phenomena and premorbid anancastic personality traits.

PMID- 11585714
TI  - Season of birth, gender and negative symptoms in schizophrenia.
AB  - The aim of this study was to ascertain whether the symptom profile distinguishes
      between schizophrenic patients born in the winter and early spring and those born
      in other seasons. The sample consisted of 204 patients with a DSM-III-R diagnosis
      of schizophrenia who had been hospitalized for acute psychotic decompensation.
      Symptom ratings were based on the Positive and Negative Syndrome Scale (PANSS).
      The use of demographic and anamnestic data as dependent variables did not detect
      any season-of-birth effect. In contrast, clear gender-specific differences
      emerged from the comparison focusing on symptom dimensions and clinical subtype.
      Female patients born in the winter and early spring had higher scores on the
      PANSS negative scale and anergia factor whereas male patients born in other
      seasons had higher scores on the PANSS anergia factor. In addition, we found a
      gender-specific association between season of birth and clinical subtype. Most
      paranoid female patients were born in the non-winter months whereas, among men, a
      slightly higher percentage of paranoid patients were born in winter months. These
      results suggest that gender plays a role in modulating the effect of the season
      of birth on symptoms of schizophrenia.

PMID- 11585715
TI  - Clinical features of panic attacks in schizophrenia.
AB  - Since reports have underscored that panic attacks (PA) may be an identifiable
      state occurring in schizophrenia, we studied the symptomatology of PA in a group
      of schizophrenic patients. Of 40 patients (21 males and 19 females) attending a
      clinic for maintenance therapy of schizophrenia, 19 (36.8%) had a lifetime
      history of PA. Seven among those 19 patients (36.8%) had or had had spontaneous
      panic attacks, not related to phobic fears or delusional fears, and for the 12
      remaining patients, the PA were related to paranoid ideas. Moreover, the paranoid
      subtype of schizophrenia tends to be more often associated with a history of
      panic attack than other subtypes of schizophrenia (52.6% vs 23.8%; chi2 = 3.5, P
      =.06). It seems that there are at least two types of PA in schizophrenic
      patients. The first one could be independent from the psychotic feature, with no
      psychopathological link. The second kind of PA could be directly related to a
      schizophrenic disorder, and found in patients with the paranoid subtype.

PMID- 11585716
TI  - Neuropsychological correlates of schizophrenic syndromes in patients treated with
      atypical neuroleptics.
AB  - There is widespread evidence that schizophrenic symptomatology is best
      represented by three syndromes (positive, negative, disorganized). Both the
      disorganized and negative syndrome have been found to correlate with several
      neurocognitive dysfunctions. However, previous studies investigated samples
      predominantly treated with typical neuroleptics, which frequently induce
      parkinsonian symptoms that are hard to disentangle from primary negative symptoms
      and may have inflated correlations with neurocognition. A newly developed
      psychopathological instrument called the Positive and Negative and Disorganized
      Symptoms Scale (PANADSS) was evaluated in 60 schizophrenic patients. Forty-seven
      participants treated with atypical neuroleptics performed several neurocognitive
      tasks.A three-factor solution of schizophrenic symptomatology emerged. Negative
      symptomatology was associated with diminished creative verbal fluency and digit
      span backward, whereas disorganization was significantly correlated with impaired
      Stroop, WCST and Trail-Making Test B performance.Data suggest that
      disorganization is associated with tasks that demand executive functioning.
      Previous findings reporting correlations between negative symptomatology and
      neurocognition may have been confounded by the adverse consequences of typical
      neuroleptics.

PMID- 11585717
TI  - Personality traits in treated Wilson's disease determined by means of the
      Karolinska Scales of Personality (KSP).
AB  - OBJECTIVE: The aim was to elucidate the personality traits of patients with
      treated Wilsons disease (WD) in comparison to healthy volunteers. METHOD: Twenty
      five WD patients, ten females and 15 males, with a mean age of 35.2 +/- 8.3 years
      completed the Karolinska Scales of Personality (KSP), a self-report inventory
      comprising 15 separate scales. The results were compared to a control series
      comprising 200 men and 200 women drawn from the general population. RESULTS: The
      patients with treated WD scored significantly lower than the healthy controls on
      aggressivity-hostility-related scales and the scale measuring Psychic Anxiety.
      Patients with predominantly hepatic symptoms had the lowest aggressivity-related
      scores and patients with predominantly neurological symptoms had the lowest
      Irritability, Guilt and Detachment scores and the highest Impulsiveness and
      Muscular Tension scores. Both groups scored low on the Somatic Anxiety scale.
      CONCLUSION: The present results illustrate that patients with treated WD have
      significant deviations in personality traits, especially in aggressivity
      hostility-related scales and Psychic Anxiety, compared to healthy controls when
      investigated by means of a self-report inventory, the KSP. The deviations were
      not related to age, age at onset or duration of the disease.

PMID- 11585718
TI  - Constitutive expression of ErbB-2 in gallbladder epithelium results in
      development of adenocarcinoma.
AB  - Overexpression of ErbB-2 in the basal layer of biliary tract epithelium led to
      the development of gallbladder adenocarcinoma in 100% of transgenic mice by 3
      months of age. In addition, tumors developed in other parts of the biliary tree
      (e.g., cholangiocarcinoma). Adenocarcinoma of the gallbladder appeared to arise
      via a stepwise process involving hyperplasia, adenoma formation, and then
      adenocarcinoma formation. Increased ErbB-2/epidermal growth factor receptor
      heterodimer formation, activation of mitogen-activated protein kinase, and up
      regulation of cyclooxygenase-2 levels (mRNA and protein) were observed in
      gallbladder epithelium of these mice. These mice represent a unique new animal
      model for studying biliary tract carcinogenesis.

PMID- 11585719
TI  - BARX2 induces cadherin 6 expression and is a functional suppressor of ovarian
      cancer progression.
AB  - The human homeobox BARX2 is located at 11q24-q25, within a minimal region
      associated with frequent loss of heterozygosity and adverse survival in
      epithelial ovarian cancer. BARX2 is a transcription factor that regulates
      transcription of specific cell adhesion molecules in the mouse. We show that
      BARX2 and cadherin 6 are expressed in normal human ovarian surface epithelium.
      BARX2 and cadherin 6 both have significantly lower expression in a clinical
      sample of endometrioid and clear cell ovarian cancers, as compared with serous or
      mixed mesodermal tumors. In a series of ovarian cancer cell lines, BARX2
      expression showed a significant direct correlation with cadherin 6 expression. In
      OAW42, an ovarian cancer cell line that does not endogenously express BARX2, in
      vitro transfection of human BARX2 cDNA induced cadherin 6 expression.
      Transfection of BARX2 into OAW42 inhibited Matrigel invasion, haptotactic
      cellular migration to a collagen IV signal, and adhesion to collagen IV-coated
      plates. Our data demonstrate that BARX2 is expressed in the ovarian surface
      epithelium and has functional suppressor properties in ovarian cancer cells.

PMID- 11585720
TI  - SKY1 is involved in cisplatin-induced cell kill in Saccharomyces cerevisiae, and
      inactivation of its human homologue, SRPK1, induces cisplatin resistance in a
      human ovarian carcinoma cell line.
AB  - The therapeutic potential of cisplatin, one of the most active and widely used
      anticancer drugs, is severely limited by the occurrence of cellular resistance.
      In this study, using budding yeast Saccharomyces cerevisiae as a model organism
      to identify novel drug resistance genes, we found that disruption of the yeast
      gene SKY1 (serine/arginine-rich protein-specific kinase from budding yeast) by
      either transposon insertion or one-step gene replacement conferred cellular
      resistance to cisplatin. Heterologous expression of the human SKY1 homologue
      SRPK1 (serine/arginine-rich protein-specific kinase) in SKY1 deletion mutant
      yeast cells restored cisplatin sensitivity, suggesting that SRPK1 is a cisplatin
      sensitivity gene, the inactivation of which could lead to cisplatin resistance.
      Subsequently, we investigated the role of SRPK1 in cisplatin sensitivity and
      resistance in human ovarian carcinoma A2780 cells using antisense
      oligodeoxynucleotides. Treatment of A2780 cells with antisense
      oligodeoxynucleotides directed against the translation initiation site of SRPK1
      led to down-regulation of SRPK1 protein and conferred a 4-fold resistance to
      cisplatin. The human SRPK1 gene has not been associated with drug resistance
      before. Our new findings strongly suggest that SRPK1 is involved in cisplatin
      induced cell kill and indicate that SRPK1 might potentially be of importance for
      studying clinical drug resistance.

PMID- 11585721
TI  - Plasmids with a mammalian replication origin and a matrix attachment region
      initiate the event similar to gene amplification.
AB  - Gene amplification plays a crucial role in the development of many human
      malignancies. Amplified genes are frequently localized on double minutes (DMs).
      We show here that plasmids bearing both a mammalian replication origin and a
      nuclear matrix attachment region were able to integrate into DMs if transfected
      to cells having DMs (COLO 320DM). Furthermore, these plasmids triggered the
      events leading to the de novo formation of the structure similar to DMs if
      transfected to the cells without DMs (COLO 320HSR or HeLa). Autonomous
      replication of these plasmids was suggested to be a prerequisite for these events
      to occur, because the presence of the origin sequences in the plasmids was
      required. The presence of matrix attachment region in the plasmids is also
      required for these events to occur, suggesting that matrix attachment plays an
      indispensable role in extrachromosomal replication. This model system will allow
      us to investigate the mechanism of gene amplification as well as to analyze the
      autonomous replication of the plasmid with mammalian replication origins.

PMID- 11585722
TI  - Age-related hypermethylation of the 5' region of MLH1 in normal colonic mucosa is
      associated with microsatellite-unstable colorectal cancer development.
AB  - Hypermethylation of the MLH1 promoter underlies most sporadic colorectal cancers
      with microsatellite instability (MSI). To investigate the role of
      hypermethylation in the normal colonic mucosa as a possible precursor lesion, we
      studied 700 bp upstream of MLH1 covering 51 CpG sites. We found partially
      methylated alleles in 15 of 34 (44%) patients <60 years of age and 20 of 24 (83%)
      patients > or =80 years of age (P = 0.0026). Fully methylated alleles were
      present in 18 of 33 (55%) patients with MSI+ tumors but in only 18 of 90 (20%)
      patients with MSI- tumors (P = 0.00019). By in situ analysis, methylation was
      patchy and located mainly in the cryptal regions close to the lumen. We conclude
      that the spread of methylation in the MLH1 promoter in the normal colonic mucosa
      is closely associated with age and the development of sporadic MSI+ colorectal
      cancers.

PMID- 11585723
TI  - Secreted and cell surface genes expressed in benign and malignant colorectal
      tumors.
AB  - Serial analysis of gene expression was used to identify transcripts encoding
      secreted or cell surface proteins that were expressed in benign and malignant
      tumors of the colorectum. A total of 290,394 tags were analyzed from normal,
      adenomatous, and cancerous colonic epithelium. Of the 21,343 different
      transcripts observed, 957 were found to be differentially expressed between
      normal tissue and adenoma or between normal tissue and cancer. Forty-nine
      transcripts were elevated > or =20-fold in adenomas, 40 transcripts were elevated
      > or =20-fold in cancers, and 9 transcripts were elevated > or =20-fold in both.
      Products of six of these nine transcripts (TGFBI, LYS, RDP, MIC-1, REGA, and
      DEHL) were predicted to be secreted or to reside on the cell surface, and these
      were analyzed in more detail. The abnormal expression levels predicted by serial
      analysis of gene expression were confirmed by quantitative PCR analyses of each
      of these six genes. Moreover, the cell types responsible for the elevated
      expression were identified by in situ hybridization and by PCR analyses of
      epithelial cells immunoaffinity purified from primary tumors. This study extends
      knowledge of the differences in gene expression that underlie various stages of
      neoplasia and suggests specific diagnostic approaches that may be useful for the
      early detection of colorectal neoplasia.

PMID- 11585724
TI  - Complete inhibition of vascular endothelial growth factor (VEGF) activities with
      a bifunctional diabody directed against both VEGF kinase receptors, fms-like
      tyrosine kinase receptor and kinase insert domain-containing receptor.
AB  - Vascular endothelial growth factor (VEGF) binds to and mediates its activity
      mainly through two tyrosine kinase receptors, VEGF receptor 1 [or fms-like
      tyrosine kinase receptor (Flt-1)] and VEGF receptor 2 [or kinase insert domain
      containing receptor (KDR)]. Numerous studies have shown that overexpression of
      VEGF and its receptor plays an important role in tumor-associated angiogenesis
      and hence in both tumor growth and metastasis. We demonstrated previously that
      antagonistic antibodies to KDR specifically inhibited VEGF-stimulated receptor
      activation, cell migration, and endothelial cell mitogenesis. Here we constructed
      a recombinant bifunctional diabody that is capable of blocking both Flt-1 and KDR
      from binding to their ligands, including VEGF and placenta growth factor (PlGF).
      The diabody was expressed in Escherichia coli and purified by single-step
      affinity chromatography. The diabody retained the capacity to bind both KDR and
      Flt-1 and effectively blocked interaction between KDR and VEGF, Flt-1 and VEGF,
      and Flt-1 and PlGF. Furthermore, the diabody is a stronger inhibitor than its
      parent antibodies to VEGF-stimulated mitogenesis of human endothelial cells, as
      well as both VEGF- and PlGF-induced migration of human leukemia cells. Taken
      together, our results suggest that dual receptor blockade with the bifunctional
      diabody may prove to be a more efficient approach in inhibiting VEGF-stimulated
      angiogenesis.

PMID- 11585725
TI  - Adenovirus-mediated transfection of caspase-8 augments anoikis and inhibits
      peritoneal dissemination of human gastric carcinoma cells.
AB  - Caspase-8 is a member of the cysteine protease family that modulates apoptosis
      induced by a variety of cell death signals and has recently been found to be
      activated during the process of anoikis, which is a form of apoptosis caused by
      loss of anchorage in epithelial cells. We previously demonstrated that the
      inhibition of anoikis promotes peritoneal dissemination of human gastric
      carcinoma MKN45 cells, which are anchorage dependent. This suggests that
      augmentation of anoikis may suppress dissemination of carcinoma cells. To
      determine whether extrinsic overexpression of caspase-8 can augment anoikis in
      MKN45 cells, we transfected them with the caspase-8 gene using an adenoviral
      (Adv) vector (Adv-caspase-8). Here we demonstrate that Adv-caspase-8 infection,
      at 15 multiplicity of infection (MOI), can augment anoikis in MKN45 cells and
      suppresses MKN45 peritoneal dissemination in SCID mice. The inhibitory effect on
      peritoneal dissemination resulted in a prolonged survival compared with that in
      control mice. In contrast, the Adv-caspase-8 (15 MOI) had no distinct effect on
      cell viability or growth either of attached MKN45 cells or of s.c. tumor growth
      in SCID mice. Thus, Adv-mediated overexpression of caspase-8 suppressed
      peritoneal dissemination mainly through augmentation of anoikis. In addition, Adv
      caspase-8-mediated augmentation of anoikis was similarly observed in another
      gastric carcinoma MKN74 cell line. In contrast, Adv-p53 could not augment anoikis
      in MKN45 cells. These results imply that Adv-mediated gene transfer of caspase-8
      can selectively induce apoptosis in detached carcinoma cells and, thus, shows
      potential as a novel cancer therapy against dissemination of gastric and probably
      other carcinoma cells originating from epithelial tissues.

PMID- 11585726
TI  - Identification of a mononucleotide repeat as a major target for mitochondrial DNA
      alterations in human tumors.
AB  - Mitochondrial DNA (mtDNA) mutations scattered through coding and noncoding
      regions have been reported in cancer. The mechanisms that generate such mutations
      and the importance of mtDNA mutations in tumor development are still not clear.
      Here we present the identification of a specific and highly polymorphic
      homopolymeric C stretch (D310), located within the displacement (D) loop, as a
      mutational hotspot in primary tumors. Twenty-two % of the 247 primary tumors
      analyzed harbored somatic deletions/insertions at this mononucleotide repeat.
      Moreover, these alterations were also present in head and neck preneoplastic
      lesions. We further characterized the D310 variants that appeared in the lung and
      head and neck tumors. Most of the somatic alterations found in tumors showed
      deletion/insertions of 1- or 2-bp generating D310 variants identical to
      constitutive polymorphisms described previously. Sequencing analysis of
      individual clones from lymphocytes revealed that patients with D310 mutations in
      the tumors had statistically significant higher levels of D310 heteroplasmy (more
      than one length variant) in the lymphocyte mtDNA as compared with the patients
      without D310 mutations in the tumor mtDNA. On the basis of our observations, we
      propose a model in which D310 alterations are already present in normal cells and
      achieve homoplasmy in the tumor through a restriction/amplification event
      attributable to random genetic drift and clonal expansion.

PMID- 11585727
TI  - A nonsense mutation in MLH1 causes exon skipping in three unrelated HNPCC
      families.
AB  - Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 are responsible
      for the majority of hereditary nonpolyposis colorectal cancer (HNPCC) families. A
      common mutation mechanism is to disrupt MLH1 and MSH2 mRNA splicing. The
      disruption creates aberrant mRNAs lacking specific coding exons (exon skipping).
      Here, we report a novel skipping of MLH1 exon 12 caused by an AAG to TAG nonsense
      mutation at codon 461 in three HNPCC families of North American origins. The
      nonsense codon was found in a conserved haplotype in the three unrelated families
      and seems to represent a founder mutation. The skipping created an aberrant MLH1
      mRNA transcript lacking exon 12. The effect of the codon 461 nonsense mutation on
      exon 12 skipping is evident even though it was placed in a minigene construct
      containing entirely different coding sequences. Notably, the effect of the
      nonsense mutation on exon skipping is incomplete. Accordingly, a second aberrant
      MLH1 transcript encompassing the nonsense codon is also produced. Whereas the
      latter transcript is unstable, presumably because of nonsense-mediated mRNA
      decay, neither of the aberrant transcripts seems to affect the stability of wild
      type MLH1 mRNA. This study demonstrates that the germ-line nonsense mutation at
      codon 461 of MLH1 disrupts normal MLH1 mRNA processing, and that exon skipping
      underlies pathogenesis in these HNPCC families.

PMID- 11585728
TI  - Synergistic activation of functional estrogen receptor (ER)-alpha by DNA
      methyltransferase and histone deacetylase inhibition in human ER-alpha-negative
      breast cancer cells.
AB  - Formation of transcriptional repression complexes such as DNA methyltransferase
      (DNMT) 1/histone deacetylase (HDAC) or methyl-CpG binding protein/HDAC is
      emerging as an important mechanism in silencing a variety of methylated tissue
      specific and imprinted genes. Our previous studies showed that treatment of
      estrogen receptor (ER)-alpha-negative human breast cancer cells with the DNMT
      inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) led to ER mRNA and protein re
      expression. Also, the HDAC inhibitor trichostatin A (TSA) could induce ER
      transcript about 5-fold. Here we show that 5-aza-dC alone induced ER transcript
      about 30-40-fold, and the addition of TSA elevated ER mRNA expression about 10
      fold more in the human ER-negative breast cancer cell lines MDA-MB-231 and MDA-MB
      435. Overall, the combination of 5-aza-dC and TSA induced a 300-400-fold increase
      in ER transcript. Restoration of estrogen responsiveness was demonstrated by the
      ability of the induced ER protein to elicit estrogen response element-regulated
      reporter activity from an exogenous plasmid as well as induce expression of the
      ER target gene, progesterone receptor. The synergistic activation of ER occurs
      concomitantly with markedly reduced soluble DNMT1 expression and activity,
      partial demethylation of the ER CpG island, and increased acetylation of histones
      H(3) and H(4). These data suggest that the activities of both DNMT1 and HDAC are
      key regulators of methylation-mediated ER gene silencing.

PMID- 11585729
TI  - Substitutions that compromise the ionizing radiation-induced association of p53
      with 14-3-3 proteins also compromise the ability of p53 to induce cell cycle
      arrest.
AB  - Ionizing radiation (IR) induces an increase in the levels and activity of the p53
      tumor suppressor protein. The increased activity is attributed to IR-induced
      posttranslational modifications, some of which regulate the interaction of p53
      with other proteins. One of these modifications is dephosphorylation of Ser(376),
      which leads to association of p53 with 14-3-3 proteins. To establish the
      significance of this interaction, we examined the function of mutant p53 proteins
      that do not interact with 14-3-3 proteins in vivo. These p53 mutants retained
      sequence-specific DNA binding activity. However, their ability to activate
      transcription of the endogenous p21/waf1/cip1 gene and to induce G(1) arrest was
      compromised, suggesting that the dephosphorylation of Ser(376) and the
      association of p53 with 14-3-3 proteins contribute to the activation of p53 in
      response to IR.

PMID- 11585730
TI  - Frequent epigenetic inactivation of RASSF1A by aberrant promoter hypermethylation
      in human gastric adenocarcinoma.
AB  - Methylation associated inactivation of RASSF1, a putative tumor suppressor
      identified at 3p21.3, has been frequently observed in several human malignancies,
      including lung and breast cancers. To explore the penetrance of RASSF1 in gastric
      carcinogenesis, we performed expression and mutation analyses of 3 isotypes of
      RASSF1 (A, B, and C) in 150 gastric specimens, including 15 carcinoma cell lines.
      RASSF1A and RASSF1B transcripts were not expressed in 60% (9 of 15) and 33% (5 of
      15) of gastric carcinoma cell lines, respectively, whereas RASSF1C was detectable
      in all cell lines. Bisulfite DNA sequencing analysis revealed that the CpG island
      in the RASSF1A promoter is hypermethylated in all RASSF1A-nonexpressing cell
      lines. In addition, both RASSF1A and RASSF1B were re-expressed by treatment with
      the demethylating agent 5-aza-2'-deoxycytidine. Among 90 primary gastric
      adenocarcinomas examined, 41 (46%) and 19 (21%) expressed no or abnormally low
      levels of RASSF1A and RASSF1B, respectively, and 12 (13%) tumors showed no
      expression of both isoforms. Loss or abnormal down-regulation of RASSF1A
      correlated with tumor stage and grade but not with histological types of tumors.
      Methylation-specific PCR analysis demonstrated that 95% (39 of 41) of RASSF1A
      nonexpressing primary tumors are methylated at the CpG sites in the promoter,
      whereas none of the adjacent noncancerous or normal tissues are methylated. No
      somatic mutations were detected in RASSF1 transcripts expressed in unmethylated
      tumors. However, 10 methylated tumors, including 4 cell lines, showed low genomic
      levels of RASSF1 and expressed no RASSF1A transcripts, suggesting that RASSF1A
      inactivation might be caused by both epigenetic and genetic mechanisms in a
      subset of gastric adenocarcinomas. In conclusion, our data indicate that
      epigenetic transcriptional silencing of RASSF1, especially RASSF1A isoform, is a
      frequent event in gastric tumorigenesis and might play an important role in the
      malignant progression of gastric adenocarcinomas.

PMID- 11585731
TI  - Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic
      medulloblastomas.
AB  - Medulloblastoma (MB) represents the most frequent malignant brain tumor in
      children. Most MBs appear sporadically; however, their incidence is highly
      elevated in two inherited tumor predisposition syndromes, Gorlin's and Turcot's
      syndrome. The genetic defects responsible for these diseases have been
      identified. Whereas Gorlin's syndrome patients carry germ-line mutations in the
      patched (PTCH) gene, Turcot's syndrome patients with MBs carry germ-line
      mutations of the adenomatous polyposis coli (APC) gene. The APC gene product is a
      component of a multiprotein complex controlling beta-catenin degradation. In this
      complex, Axin plays a major role as scaffold protein. Whereas APC mutations are
      rare in sporadic MBs, a hot-spot region of beta-catenin (CTNNB1) mutations was
      identified in a subset of MBs. To find out if Axin is also involved in the
      pathogenesis of sporadic MBs, we analyzed 86 MBs and 11 MB cell lines for
      mutations in the AXIN1 gene. Using single-strand conformation polymorphism
      analysis, screening for large deletions by reverse transcription-PCR, and
      sequencing analysis, a single somatic point mutation in exon 1 (Pro255Ser) and
      seven large deletions (12%) of AXIN1 were detected. This indicates that AXIN1 may
      function as a tumor suppressor gene in MBs.

PMID- 11585732
TI  - High expression of S-phase kinase-interacting protein 2, human F-box protein,
      correlates with poor prognosis in oral squamous cell carcinomas.
AB  - Reduced expression of p27(Kip1), a cyclin-dependent kinase (Cdk) inhibitor, is
      frequently found in various cancers, including oral squamous cell carcinoma
      (OSCC), and is attributable to an enhancement of its degradation. Skp2, an F-box
      protein necessary for DNA replication, is required for the ubiquitinylation and
      subsequent degradation of p27(Kip1). In the present study, we examined the
      expression of Skp2 and its correlation with the expression of p27(Kip1) protein
      or p27(Kip1) degradation in OSCC. Using immunohistochemistry, we found that high
      expression of Skp2 was present in 49% of OSCCs and only 20% of epithelial
      dysplasias. Significantly, high expression of Skp2 was correlated with poor
      prognosis of OSCC patients. We also found an inverse correlation between the
      expression of Skp2 and p27 by immunohistochemical analysis. A similar correlation
      was observed in OSCC cell lines and OSCC tissues by Western blot analysis.
      Interestingly, OSCC tissues with Skp2 expression had high p27(Kip1) degradation
      activity. These findings indicate that (a) Skp2 may play an important role for
      the development of OSCC, (b) Skp2 can be a novel target for OSCC treatment as
      well as a strong prognostic marker, and (c) the reduction in p27(Kip1) protein
      may be brought about by enhancement of its degradation mediated by increased
      levels of Skp2 protein.

PMID- 11585733
TI  - In vivo intracellular signaling as a marker of antiangiogenic activity.
AB  - Alterations in endothelial cell (EC) signaling could serve as a marker of
      effective antiangiogenic therapy. We determined the effect of an antiangiogenic
      tyrosine kinase inhibitor, SU6668, on tumor EC signaling in liver metastases in
      mice. In vitro immunofluorescence verified that pretreatment of ECs with SU6668
      before exposure to VEGF decreased in vitro phosphorylation of Erk and Akt. Using
      double-fluorescence immunohistochemistry, phosphorylated Erk and Akt were
      constitutively expressed in ECs in liver metastases in untreated mice, but SU6668
      blocked activation of these signaling intermediates. Determining the activation
      status of the Erk and Akt signaling pathways in tumor ECs may serve as a
      surrogate marker for the effectiveness of antiangiogenic regimens.

PMID- 11585734
TI  - Therapeutic efficacy of E2F1 in pancreatic cancer correlates with TP73 induction.
AB  - Pancreatic cancer is particularly resistant to apoptosis by antineoplastic
      agents, which is partly attributable to the lack of functional p53. Here we show
      that E2F1 in combination with the most clinically efficient drug, gemcitabine,
      resulted in a strong induction of apoptosis independent of functional p53,
      whereas the effect of either therapy alone varied between different cell lines.
      Intratumoral injection of a helper-dependent adenovirus vector expressing E2F1
      plus drug treatment resulted in a significant reduction of tumor volume. The
      therapeutic effect is directly correlated with the induction of the p53 homologue
      p73, suggesting that the recently discovered E2F1/p73 pathway plays a critical
      role in cancer therapy.

PMID- 11585735
TI  - Brain enriched hyaluronan binding (BEHAB)/brevican increases aggressiveness of
      CNS-1 gliomas in Lewis rats.
AB  - Gliomas are the most common primary intracranial tumors. One extracellular matrix
      component that has been implicated in glial tumor biology is brain enriched
      hyaluronan binding (BEHAB)/brevican. In this study, the CNS-1 rat glioma cell
      line was transfected with a vector containing either a full-length BEHAB/brevican
      cDNA, a 5' insert encoding the NH(2)-terminal BEHAB/brevican cleavage product, or
      a 3' insert encoding the COOH-terminal cleavage product. As a control, CNS-1
      cells were transfected with green fluorescent protein. Rats with intracranial
      grafts of BEHAB/brevican-transfected CNS-1 cells displayed significantly shorter
      survival times than did rats with CNS-green fluorescent protein intracranial
      grafts (P < 0.001). Histological examination showed that the BEHAB/brevican
      transfected tumors were just as, if not more, aggressive than control tumors,
      even though the BEHAB/brevican tumors had been growing for only approximately two
      thirds the time as long as control tumors. These data suggest that up-regulation
      and proteolytic cleavage of BEHAB/brevican increase significantly the
      aggressiveness of glial tumors. It will be important to investigate the effect of
      inhibiting cleavage of BEHAB/brevican in these cells and to determine the
      therapeutic potential of inhibiting BEHAB/brevican cleavage in gliomas.

PMID- 11585736
TI  - Suppression of intestinal and mammary neoplasia by lifetime administration of
      aspirin in Apc(Min/+) and Apc(Min/+), Msh2(-/-) mice.
AB  - Numerous studies have indicated that exposure to nonsteroidal anti-inflammatory
      drugs is associated with a lowered risk of colorectal cancer. However, analyses
      of the effect of aspirin upon tumorigenesis in Apc(Min/+) mice have yielded
      contrasting results. We show that adult dietary exposure to aspirin does not
      suppress intestinal tumorigenesis in Apc(Min/+) mice, but that continual exposure
      from the point of conception does. To test whether this regime could suppress the
      phenotype of murine models of hereditary nonpolyposis colorectal cancer, Msh2
      deficient mice were exposed to aspirin. This did not modify the mutator phenotype
      of Msh2(-/-) mice, but weakly extended survival. Finally, we analyzed
      (Apc(Min/+), Msh2(-/-)) mice and found that lifetime aspirin exposure
      significantly delayed the onset of both intestinal and mammary neoplasia. Thus
      embryonic and perinatal exposure to aspirin suppresses neoplasia specifically
      associated with the loss of Apc function, opening a potential window of
      opportunity for nonsteroidal anti-inflammatory drug intervention.

PMID- 11585737
TI  - Retinoic acid biosynthesis by normal human breast epithelium is via aldehyde
      dehydrogenase 6, absent in MCF-7 cells.
AB  - Retinoic acid (RA) is the form of vitamin A that controls differentiation and
      proliferation of epithelia. Our previous work established that normal breast
      epithelia synthesize RA from retinol, an ability retained by three immortalized
      but nontumorigenic cell lines but lost in five of six breast cell lines. In this
      work, we characterize the cause of this defect in one of the lines, the MCF-7
      line. We have determined that the immortalized but nontumorigenic cell line,
      MTSV1.7, capable of synthesizing RA from both retinol and retinal, contains a
      retinaldehyde dehydrogenase activity for the second step in RA biosynthesis. We
      have identified it, after isolation, as a previously described enzyme, aldehyde
      dehydrogenase 6 (ALDH6). Immunohistochemical analysis of normal human breast with
      antibodies to ALDH6 showed expression of this enzyme in the glandular epithelia
      colocalized with cellular RA-binding protein type II, a possible marker for
      certain cells able to synthesize RA. ALDH6 was not present in MCF-7 cells, and
      these cells were unable to oxidize retinal to RA in culture. When MCF-7 cells
      were then transfected with ALDH6, they (re)gained the ability to oxidize retinal
      to RA as well as some ability to synthesize RA when provided with retinol. This
      suggests that loss of ALDH6 expression is the defect in RA biosynthesis in these
      cells. Identification of ALDH6 as the retinaldehyde dehydrogenase present in
      normal human breast epithelia provides the first tool necessary for studying the
      loss of RA synthetic ability in cancer cells and the relationship of this process
      to malignant transformation.

PMID- 11585738
TI  - Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human
      prostate cancer cell line.
AB  - The effects of selenium exposure were studied in LNCaP human prostate cancer
      cells, and this same cell line adapted to selenium over 6 months to compare acute
      versus chronic effects of sodium selenite, the latter most closely resembling
      human clinical trials on the effects of selenium in cancer prevention and
      therapy. Our results demonstrated that oxidative stress was induced by sodium
      selenite at high concentrations in both acute and chronic treatments, but
      outcomes were different. After acute exposure to selenite, cells exhibited
      mitochondrial injury and cell death, mainly apoptosis. After chronic exposure to
      selenite, cells showed growth inhibition caused by cell cycle arrest, increased
      numbers of mitochondria and levels of mitochondrial enzymes, and only minimal
      induction of apoptosis. Immunoblotting analysis revealed that multiple proteins
      were up-regulated by chronic exposure to selenite. Among them, only up-regulation
      of manganese superoxide dismutase and the cyclin-dependent kinase inhibitor
      p21(Waf1/Cip1), proteins known to be redox sensitive and to have cell cycle
      regulatory functions, correlated with cell growth inhibition. Our results in
      selenite-adapted cells suggest that selenium may exert its effects in human
      prostate cancer cells by altering intracellular redox state, which subsequently
      results in cell cycle block.

PMID- 11585739
TI  - Inhibition of focal adhesion kinase expression or activity disrupts epidermal
      growth factor-stimulated signaling promoting the migration of invasive human
      carcinoma cells.
AB  - Elevated focal adhesion kinase (FAK) expression in human tumor cells has been
      correlated with an increased cell invasion potential. In cell culture, studies
      with FAK-null fibroblasts have shown that FAK function is required for cell
      migration. To determine the role of elevated FAK expression in facilitating
      epidermal growth factor (EGF)-stimulated human adenocarcinoma (A549) cell
      motility, antisense oligonucleotides were used to reduce FAK protein expression
      >75%. Treatment of A549 cells with FAK antisense (ISIS 15421) but not a
      mismatched control (ISIS 17636) oligonucleotide resulted in reduced EGF
      stimulated p130(Cas)-Src complex formation, c-Jun NH(2)-terminal kinase (JNK)
      activation, directed cell motility, and serum-stimulated cell invasion through
      Matrigel. Because residual FAK protein in ISIS 15421-treated A549 cells was
      highly phosphorylated at the Tyr-397/Src homology (SH)2 binding site, expression
      of the FAK COOH-terminal domain (FRNK) was also used as an inhibitor of FAK
      function. Adenoviral-mediated infection and expression of FRNK promoted FAK
      dephosphorylation at Tyr-397, resulted in reduced EGF-stimulated JNK as well as
      extracellular-regulated kinase 2 (ERK2) kinase activation, inhibited matrix
      metalloproteinase-9 (MMP-9) secretion, and potently blocked both random and EGF
      stimulated A549 cell motility. Equivalent expression of a FRNK (S-1034) point
      mutant that did not promote FAK dephosphorylation also did not affect EGF
      stimulated signaling or cell motility. Dose-dependent reduction in EGF-stimulated
      A549 motility was observed with the PD98059 MEK1 inhibitor and the batimastat (BB
      94) inhibitor of MMP activity, but not with the SB203580 inhibitor of p38 kinase.
      Finally, comparisons between normal, FAK-null, and FAK-reconstituted fibroblasts
      revealed that FAK enhanced EGF-stimulated JNK and ERK2 kinase activation that was
      required for cell motility. These data indicate that FAK functions as an
      important signaling platform to coordinate EGF-stimulated cell migration in human
      tumor cells and support a role for inhibitors of FAK expression or activity in
      the control of neoplastic cell invasion.

PMID- 11585740
TI  - Collagenase-3 expression in breast myofibroblasts as a molecular marker of
      transition of ductal carcinoma in situ lesions to invasive ductal carcinomas.
AB  - Collagenase-3 (matrix metalloproteinase 13; MMP-13), a protease originally
      identified in breast carcinoma, is characterized by a potent degrading activity
      against a wide spectrum of extracellular matrix proteins. The aims of this study
      were to localize and identify the MMP-13-expressing cells in invasive human
      breast carcinoma and to evaluate the role of MMP-13 in transition to invasive
      lesions by studying ductal carcinoma in situ (DCIS). We found expression of MMP
      13 in stromal fibroblast-like cells in all 21 invasive ductal carcinomas studied
      and in 4 of 9 invasive lobular carcinomas. In most carcinomas, expression of MMP
      13 was limited to small stromal foci in the tumor area. Combined in situ
      hybridization and immunohistochemistry showed coexpression of alpha-smooth muscle
      actin immunoreactivity and MMP-13 mRNA in myofibroblasts. In contrast,
      cytokeratin-positive cancer cells, alpha-smooth muscle actin-positive vascular
      smooth muscle cells, CD68-positive macrophages, and CD31-positive endothelial
      cells were all MMP-13 mRNA negative. In situ hybridization for MMP-13 in 17 DCIS
      lesions revealed expression in 10 cases. Immunohistochemical analysis of all DCIS
      cases identified microinvasion in 8 of the 17 lesions. Seven of the eight lesions
      with microinvasion were MMP-13 positive. Further analysis showed that MMP-13
      expression was often associated with the microinvasive events. This particular
      expression pattern was unique for MMP-13 among other MMPs analyzed, including MMP
      2, -11, and -14. We conclude that MMP-13 is primarily expressed by myofibroblasts
      in human breast carcinoma and that expression in DCIS lesions often is associated
      with microinvasive events. On the basis of these data, we propose that MMP-13 may
      play an essential role during transition of DCIS lesions to invasive ductal
      carcinomas.

PMID- 11585741
TI  - Alterations of beta- and gamma-catenin in N-butyl-N-(-4-hydroxybutyl)nitrosamine
      induced murine bladder cancer.
AB  - Abnormal degradation of beta-catenin caused by alteration of the glycogen
      synthase kinase-3beta (GSK-3beta) consensus motif is an important step for
      carcinogenesis. We hypothesize that beta- and gamma-catenin may play an important
      role in the pathogenesis of bladder cancer. We tested this hypothesis through
      analysis of beta- and gamma-catenin in both murine and human bladder cancers. A
      murine bladder cancer model was prepared by use of N-butyl-N-(-4
      hydroxybutyl)nitrosamine (BBN) in 6-week-old male B6D2F1 mice. After 4, 8, 12,
      16, 20, 24, and 28 weeks of BBN treatment, bladder specimens were harvested and
      analyzed for both protein and gene expression for beta- and gamma-catenin.
      Mutational analysis of the NH(2)-terminal regulatory domains of beta- and gamma
      catenin was performed in each specimen by PCR-single-strand conformational
      polymorphism (SSCP) analysis. Mutations were further confirmed by direct DNA
      sequencing with a dye terminator method. Human bladder cancer specimens with
      normal tissues, dysplasia, carcinoma in situ, and carcinoma of grades, 1, 2, and
      3 were also analyzed for beta- and gamma-catenin expression. beta- and gamma
      catenin were analyzed for mutations by SSCP and direct DNA sequencing.
      Intracellular accumulation of beta- and gamma-catenin was observed in 6 of 20
      invasive carcinoma specimens. There was no intracellular accumulation of beta-
      and gamma-catenin in mucosal dysplasia, papillary or nodular dysplasia, and
      carcinoma in situ specimens. On an SSCP analysis for beta-catenin, abnormal
      bandshifts were detected in two invasive carcinomas with intracellular beta
      catenin accumulation. Further sequencing revealed two mutations [AGT(S) to ATT(I)
      and TCT(S) to CCT(P)] within the consensus motif for GSK-3beta phosphorylation.
      On the other hand, SSCP analysis for gamma-catenin followed by sequencing
      revealed three mutations in two invasive carcinomas with intracellular
      accumulation of gamma-catenin. These three alterations affected the 3' downstream
      region outside the GSK-3beta phosphorylation site [ACC(T) to GCC(A), CTC(L) to
      ATC(I), and CTC(L) to ATG(M)]. In human bladder cancer, beta- and gamma-catenin
      expression was significantly weaker than in normal bladder. On SSCP analysis one
      abnormal bandshift was observed in high-grade human bladder cancer with
      intracellular beta-catenin accumulation. DNA sequencing revealed mutation TCT(S)
      to TGT(C). In summary, alterations in beta- and gamma-catenin are late events
      favoring tumor progression in mouse BBN-induced bladder cancer. Changes affecting
      the GSK-3beta phosphorylation site appear to be associated with activation of
      beta-catenin, but not with activation of gamma-catenin. In human blabber cancer,
      beta- and gamma-catenin expression is similar to the expression in the mouse
      model. The present study demonstrates that beta- and gamma-catenin may play an
      important role in bladder cancer progression.

PMID- 11585742
TI  - Methylated CpG dinucleotides are the preferential targets for G-to-T transversion
      mutations induced by benzo[a]pyrene diol epoxide in mammalian cells: similarities
      with the p53 mutation spectrum in smoking-associated lung cancers.
AB  - A large fraction of the p53 mutations in lung cancers from smokers are G-to-T
      transversions, a type of mutation that is infrequent in lung cancers from
      nonsmokers and in most other tumors. Previous studies have indicated that there
      is an association between G-to-T transversion hotspots in lung cancers and sites
      of preferential formation of polycyclic aromatic hydrocarbon adducts along the
      p53 gene. p53 codons containing methylated CpG sequences are preferential targets
      for formation of adducts by (+/-) anti-7beta,8alpha-dihydroxy-9alpha,10alpha
      epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). To assess the role of CpG
      methylation in induction of mutations by BPDE, we analyzed BPDE mutagenesis in
      three CpG methylated target genes: a supF shuttle vector and the cII and lacI
      transgenes in embryonic mouse fibroblasts. After methylation of the shuttle
      vector at all CpG sequences, 42% of all G-to-T transversions were at CpG sites
      compared with 23% in unmethylated DNA. In the cII transgene, which is methylated
      at CpG sequences in vivo, 83 of 147 (56%) of the BPDE-induced mutations were G-to
      T transversions, and 58% (48 of 83) of all G-to-T transversions occurred at
      methylated CpG sequences. In the lacI gene, 68% (75 of 111) of the BPDE-induced
      mutations were G-to-T events, and 58 of 75 (77%) of these occurred at methylated
      CpG sequences. The occurrence of transversion hotspots at methylated CpGs
      correlated with high levels of BPDE adducts formed at such sites. This situation
      mirrors the one in the p53 gene in lung cancers from smokers where 236 of 465
      (51%) of the G-to-T transversions occurred at methylated CpG sites. These
      findings further strengthen a link between polycyclic aromatic hydrocarbons
      present in cigarette smoke and lung cancer mutations and provide evidence that
      mutational processes other than C-to-T transition mutations can occur selectively
      at methylated CpG sequences.

PMID- 11585743
TI  - Evidence for a putative senescence gene locus within the chromosomal region 10p14
      p15.
AB  - High-risk human papillomavirus (HPV) types 16 and 18 are involved in the
      multistep process of cervical cancer. Transfection of normal keratinocytes with
      high-risk HPV-DNA generally gives rise to immortal cultures. This may be
      explained by the loss of senescence genes as a consequence of HPV-induced genetic
      instability. On the basis of the dominance of cellular senescence over
      immortality, fusion of normal keratinocytes with HPV-immortalized cells results
      in complementation of these putative gene defects. In a previous study, we showed
      that underrepresentation of chromosome 10 is a characteristic phenomenon during
      the early phase of immortalization. Here we show that introduction of a normal
      copy of chromosome 10 into HPV16-immortalized cells (HPKII) by Microcell-mediated
      chromosome transfer resulted in senescence of a significant number of hybrids. By
      using several derivatives of chromosome 10 for further fusion experiments, the
      chromosomal region responsible for senescence could be assigned to 10p14-p15. The
      potential significance of loss of gene function in this region is underlined by
      the high frequency (38.7%) of loss of heterozygosity in cervical cancers
      including early stage tumors.

PMID- 11585744
TI  - Growth inhibitory effects of 1alpha, 25-dihydroxyvitamin D(3) are mediated by
      increased levels of p21 in the prostatic carcinoma cell line ALVA-31.
AB  - 1alpha, 25-Dihydroxyvitamin D(3) [1alpha, 25-(OH)(2)D(3)] is recognized to have
      significant antiproliferative effects on certain prostatic carcinoma (PC) cell
      lines, although the precise mechanisms of action remain in question. We have
      evaluated the role of the cell cycle-dependent kinase inhibitor p21. In the PC
      cell lines ALVA-31 and LNCaP, 1alpha, 25-(OH)(2)D(3) inhibits growth and induces
      both p21 mRNA and protein levels. Growth inhibition of ALVA-31 cells was
      abolished by stable transfection with a p21 antisense construct. This effect was
      not attributable to a reduction in functional vitamin D receptors as measured by
      transcriptional activity with a luciferase-vitamin D response element reporter
      construct. Therefore, increased p21 expression appears necessary to mediate the
      antiproliferative effects of this hormone in ALVA-31 cells. Cell lines that are
      insensitive to the growth inhibitory properties of 1alpha, 25-(OH)(2)D(3) failed
      to up-regulate p21 expression after hormone treatment; these include sublines of
      ALVA-31 as well as the cell lines TSU-Pr1 and JCA-1. In the latter two lines,
      adenovirus-mediated expression of a sense p21 cDNA significantly reduced their
      proliferation as compared with a control adenoviral construct. This suggests that
      the signaling pathway downstream of p21 is intact in TSU-Pr1 and JCA-1 cells,
      although p21 expression appears unregulated by 1alpha, 25-(OH)(2)D(3). We propose
      a model in which the antiproliferative effect of 1alpha, 25-(OH)(2)D(3) on PC
      cells is mediated through increased p21 expression. Elucidation of why this
      effect is absent in select cell lines may provide valuable insight into the
      variability of responses observed in PC patients treated with vitamin D.

PMID- 11585745
TI  - Polymorphisms in glutathione S-transferases (GSTM1 and GSTT1) and survival after
      treatment for breast cancer.
AB  - The response to treatment for breast cancer is likely predicted by a number of
      disease and tumor tissue characteristics, many of which are under active
      investigation. One area that has received little attention is that of endogenous
      capabilities to respond to reactive oxygen species and subsequent byproducts
      resulting from radiation therapy and a number of chemotherapeutic agents,
      preventing cytotoxicity toward tumor cells. The glutathione S-transferases are
      key conjugating enzymes in this response, and GSTM1 and GSTT1 have deletion
      polymorphisms that result in no enzyme activity. In this retrospective study, we
      evaluated the role of GSTM1- and GSTT1-null genotypes on disease-free and overall
      survival among 251 women who received treatment for incident, primary breast
      cancer. Women were identified through Tumor Registry records and normal archived
      tissue retrieved for genotyping. Adjusting for age, race, and stage at diagnosis,
      women with null genotypes for GSTM1 and GSTT1 had reduced hazard of death
      [adjusted hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.36-0.97; and
      HR, 0.51; CI, 0.29-0.90, respectively] in relation to those with alleles present.
      Furthermore, women who were null for both GSTM1 and GSTT1 had one-third the
      hazard of death of those with alleles for both genes present (adjusted HR, 0.28;
      95% CI, 0.11-0.70). Similar relationships were noted for risk of recurrence.
      These data indicate that interindividual differences in activity of enzymes that
      prevent therapy-generated reactive oxidant damage may have an important impact on
      disease recurrence and overall survival.

PMID- 11585746
TI  - Dietary folate intake and breast cancer risk: results from the Shanghai Breast
      Cancer Study.
AB  - Folate is involved in DNA synthesis, repair, and methylation. It has been
      hypothesized that high intake of folate may reduce the risk of human cancers,
      including cancer of the breast. Using data from a population-based case-control
      study of breast cancer conducted in urban Shanghai during 1996-1998, we evaluated
      the association of dietary folate intake and breast cancer risk among 1321 cases
      and 1382 controls, 25-64 years of age, who never drank alcohol regularly or used
      vitamin supplements. Usual dietary habits were assessed with an in-person,
      interviewer-administered food frequency questionnaire developed and tested for
      use in this population. Unconditional logistic regression models were used to
      calculate odds ratios (ORs) and their 95% confidence intervals (95% CIs) after
      adjusting for potential confounding factors. Dietary folate intake was inversely
      associated with breast cancer risk (P for trend, 0.05) with an adjusted OR of
      0.71 (95% CI, 0.56-0.92) observed among women who were in the highest quintile of
      intake. The inverse association was stronger after further adjusting for total
      fruit and vegetable and animal food intakes (OR, 0.62; 95% CI, 0.46-0.82; P for
      trend, 0.01). A more pronounced inverse association between folate intake and
      breast cancer risk (OR, 0.47; 95% CI, 0.25-0.88; P for trend, 0.01) was observed
      among women who consumed high levels of folate cofactors (methionine, vitamin
      B(12), and vitamin B(6)) than those whose intake levels of these nutrients were
      low. Dietary intake of methionine, vitamin B(12), and vitamin B(6) were not
      independently related to risk of breast cancer after adjusting for confounding
      factors. Thus, our study adds additional support to the protective role of
      dietary folate in breast carcinogenesis and suggests further that the effect of
      folate may be modified by dietary intake of methionine, vitamin B(12), and
      vitamin B(6).

PMID- 11585747
TI  - p202, an interferon-inducible protein, mediates multiple antitumor activities in
      human pancreatic cancer xenograft models.
AB  - p202, an IFN-inducible protein, interacts with certain transcriptional activators
      leading to transcriptional repression. p202 expression has been associated with
      inhibition of cancer cell growth in vitro and in vivo. To examine a potential
      p202-mediated antitumor activity in pancreatic cancer, we used both ectopic and
      orthotopic xenograft models and demonstrated that p202 expression is associated
      with multiple antitumor activities that include inhibition of tumor growth,
      reduced tumorigenicity, prolonged survival, and remarkably, suppression of
      metastasis and angiogenesis. In vitro invasion assay also showed that p202
      expressing pancreatic cancer cells are less invasive than those without p202
      expression. That observation was supported by the findings that p202-expressing
      tumors showed reduced expression of angiogenic markers, such as interleukin 8 and
      vascular endothelial growth factor, and p202-expressing pancreatic cancer cells
      have reduced level of matrix metalloproteinase-2 activity, a secreted protease
      activity important for metastasis. Importantly, we demonstrated a treatment
      efficacy by using p202/SN2 liposome complex in a nude mice xenograft model,
      suggesting a feasibility of using the p202/SN2 liposome in future preclinical
      gene therapy experiments. Together, our results strongly suggest that p202
      expression mediates multiple antitumor activities against pancreatic cancer and
      may provide a scientific basis for developing a p202-based gene therapy in
      pancreatic cancer treatment.

PMID- 11585748
TI  - Induction of apoptosis in 9-nitrocamptothecin-treated DU145 human prostate
      carcinoma cells correlates with de novo synthesis of CD95 and CD95 ligand and
      down-regulation of c-FLIP(short).
AB  - Stimulation of CD95 leads to oligomerization of this receptor and the recruitment
      of the Fas-associated death domain (FADD) and procaspase-8 to form the death
      inducing signaling complex (DISC). Subsequent proteolytic activation of caspase-8
      at the DISC leads to the activation of downstream caspases and execution of
      apoptosis. The anticancer drug 9-nitrocamptothecin (9NC) inhibits the nuclear
      enzyme topoisomerase I (Top1), an event followed by apoptosis of cancer cells. We
      investigated whether other mechanisms downstream of the DNA-Top1-9NC complexing
      step regulate the apoptotic ability of 9NC in DU145 cells. We demonstrate that
      induction of apoptosis in DU145 cells, upon exposure to 9NC, is associated with
      de novo expression of CD95 and CD95L, suggesting that 9NC-induced apoptosis is
      mediated by the CD95 system. In this line, we observed early activation of
      procaspase-3, -7, and -8, but not -1, -9, and -10. Moreover, 9NC treatment
      resulted in the dramatic down-regulation of c-FLIP(short) expression, but not
      that of c-FLIP(long) or FADD. Furthermore, incubation of DU145 cells with a
      neutralizing antibody (NOK-1) to CD95L or transient transfection of a c
      FLIP(short) expression vector into DU145 cells partially abrogated 9NC-triggered
      apoptosis. We propose that 9NC triggers apoptosis by driving DU145 cells from a
      nonapoptotic status (c-FLIP(short)(high), CD95(low), CD95L(low)) toward a
      proapoptotic status (c-FLIP(short)(low), CD95(high), CD95L(high)). These findings
      indicate that in addition to a Top1-mediated effect, 9NC can additionally
      activate a CD95/CD95L-dependent apoptotic pathway.

PMID- 11585749
TI  - Pegylation of a chlorin(e6) polymer conjugate increases tumor targeting of
      photosensitizer.
AB  - Photodynamic therapy is emerging as a viable modality for the treatment of many
      cancers. A limiting factor in its use against intracavity tumors such as
      disseminated ovarian cancer is insufficient selectivity of the photosensitizer
      for tumor compared with normal tissue. We report on an approach to improve tumor
      targeting by exploiting differences between cell types and by chemical
      modification of a photosensitizer conjugate. Attachment of polyethylene glycol
      (pegylation) to a polyacetylated conjugate between poly-l-lysine and chlorin(e6)
      increased the relative phototoxicity in vitro toward an ovarian cancer cell line
      (OVCAR-5) while reducing it toward a macrophage cell line (J774), compared with
      the nonpegylated conjugate. Surprisingly, the increased phototoxicity of the
      pegylated conjugate correlated with reduced oxygen consumption. Pegylation also
      reduced the tendency of the conjugate to aggregate and reduced the consumption of
      oxygen when the conjugates were illuminated in solution in serum containing
      medium, suggesting a switch in photochemical mechanism from type II (singlet
      oxygen) to type I (radicals or electron transfer). Pegylation led to more
      mitochondrial localization as shown by confocal fluorescence microscopy in OVCAR
      5 cells, and, on illumination, produced a switch in cell death mechanism toward
      apoptosis not seen with J774 cells. Conjugates were injected i.p. into nude mice
      bearing i.p. OVCAR-5 tumors, and the pegylated conjugate gave higher amounts of
      photosensitizer in tumor and higher tumor:normal tissue ratios and increased the
      depth to which the chlorin(e6) penetrated into the peritoneal wall. Taken
      together, these results suggest that pegylation of a polymer-photosensitizer
      conjugate improves tumor-targeting and may increase the efficacy of photodynamic
      therapy for ovarian cancer.

PMID- 11585750
TI  - Enhanced uptake of a thermally responsive polypeptide by tumor cells in response
      to its hyperthermia-mediated phase transition.
AB  - Elastin-like polypeptides (ELPs) composed of a VPGXG repeat undergo a reversible
      phase transition in aqueous solution. They are hydrophilic and soluble in aqueous
      solution below their transition temperature (T(t)), but they become hydrophobic
      and aggregate when the temperature is raised above their T(t). In this study, we
      examine the quantitative uptake of a fluorescence-labeled, thermally responsive
      ELP as a function of ELP concentration between 5 and 15 microM in solution in
      response to hyperthermia by three cultured cancer cell lines. Flow cytometry of
      fluorescein-ELP conjugates showed that hyperthermia enhanced the cellular uptake
      of the thermally responsive ELP in human ovarian carcinoma cells (SKOV-3) and in
      HeLa cells at a concentration of 10 microM or higher, but not at a concentration
      of 5 microM, as compared with the uptake of a thermally inactive ELP control. In
      FaDu cells, hyperthermia stimulated uptake of the thermally responsive ELP at all
      solution concentrations of ELP between 5 and 15 microM. In particular, a >2-fold
      greater uptake of thermally responsive ELP compared with the thermally inactive
      control ELP was observed for FaDu cells at a solution concentration of 15 microM
      in heated cells. Confocal fluorescence microscopy of tumor cells incubated with a
      rhodamine conjugate of the thermally responsive ELP showed that the cytoplasm was
      uniformly stained below the T(t). Above the T(t), fluorescent particles were
      observed in the cytoplasm, suggesting that these particles are aggregates of the
      thermally responsive polypeptide resulting from the ELP phase transition. These
      studies demonstrate that the endocytotic uptake of a thermally responsive ELP is
      significantly enhanced by the thermally triggered phase transition of the
      polypeptide.

PMID- 11585751
TI  - Antimitogenic and proapoptotic activities of methylseleninic acid in vascular
      endothelial cells and associated effects on PI3K-AKT, ERK, JNK and p38 MAPK
      signaling.
AB  - Inhibiting the mitogenic response of vascular endothelial cells may in part
      mediate the antiangiogenic and anticancer activity of supranutritional selenium
      supplements. Our previous work had shown that methylseleninic acid (MSeA), a
      precursor of the critical anticancer methylselenol metabolite pool, was a potent
      inhibitor of the growth and survival of human umbilical vein endothelial cells
      (HUVECs). Here we investigated the effects of MSeA on selected protein kinase
      signaling transduction pathways to characterize their role in methylselenium
      induction of HUVEC cell cycle arrest and apoptosis. Exposure of asynchronous
      HUVECs for 30 h to 3-5 microM MSeA led to a profound G(1) arrest, and exposure to
      higher levels of MSeA not only led to G(1) arrest but also to DNA fragmentation
      and caspase-mediated cleavage of poly(ADP-ribose)polymerase, both biochemical
      hallmarks of apoptosis. Immunoblot analyses indicated that G(1) arrest induced by
      the sublethal doses of MSeA was associated with dose-dependent reductions of the
      levels of phospho-protein kinase B (also known as AKT or PKB), phospho
      extracellular signal regulated kinase (ERK) 1/2, and phospho-Jun NH(2)-terminal
      kinases 1/2 in the absence of any change in p38 mitogen-activated protein kinase
      (MAPK) phosphorylation. Apoptosis induced by MSeA was associated with an
      increased phosphorylation of p38 MAPK in addition to the dephosphorylation of the
      above kinases. In HUVECs deprived of endothelial cell growth supplement (ECGS)
      for 48 h, resumption of ECGS stimulation resulted in an approximately 10-fold
      increase in mitogenic response, as indicated by [(3)H]thymidine incorporation
      into DNA. The ECGS-stimulated mitogenic response was inhibited in a dose
      dependent manner by MSeA exposure with a IC(50) approximately 1 microM and a
      complete blockage at 3 microM. Wortmannin, an inhibitor of phosphatidylinositol 3
      kinase (PI3K) upstream of AKT, potently inhibited the ECGS-stimulated DNA
      synthesis (IC(50), approximately 40 nM). Combining MSeA with Wortmannin showed an
      additive antimitogenic effect. An inhibitor of MAPK/ERK kinase 1, PD98059, also
      inhibited ECGS-stimulated DNA synthesis (IC(50), approximately 55 microM), but
      combining PD98059 with MSeA had an effect similar to that when PD98059 was used
      alone. A time-course experiment indicated that PI3K (AKT and ribosomal protein S6
      kinase) activation occurred between 6 and 12 h of ECGS stimulation, and 3 microM
      MSeA exposure decreased AKT phosphorylation after 12 h of exposure, whereas no
      inhibitory effect was observed for ERK1/2 phosphorylation throughout the 30-h
      exposure duration. Additional experiments indicated that MSeA, Wortmannin, or a
      more specific PI3K inhibitor, LY294002, seemed to target, in the mid- to late
      G(1) phase, a common mechanism(s) controlling G(1) progression to S while having
      no inhibitory effect on DNA synthesis once S-phase had initiated. Taken together,
      the results support a potent inhibitory activity at achievable serum levels of
      MSeA on ECGS-stimulated mitogenesis in the mid- to late-G(1) phase, and the
      target(s) of this inhibitory activity seems to be PI3K or components of this
      signal pathway. At pharmacological levels of exposure, modulation of ERK1/2 and
      other protein kinases may be relevant for the proapoptotic action of MSeA.

PMID- 11585752
TI  - Differential expression of members of the tumor necrosis factor alpha-related
      apoptosis-inducing ligand pathway in prostate cancer cells.
AB  - Androgen ablation therapy induces apoptosis only in androgen-sensitive prostate
      cancer cells; therefore, other cytotoxic drugs are being used to induce apoptosis
      in androgen-refractory cells. Mifepristone, an antiprogestin used individually or
      together with the antiestrogen Tamoxifen, has been recommended for induction of
      cell death and treatment of several hormonal cancers. However, little is known
      about the mechanism of action of these drugs in prostate cancer. Therefore, we
      investigated the effect of Mifepristone on the tumor necrosis factor alpha
      related apoptosis-inducing ligand (TRAIL) pathway, a newly identified and very
      effective member of tumor necrosis factor-alpha family. Mifepristone and
      Tamoxifen induced significant expression of death receptors in prostate cancer
      cells in vitro and in xenografts. However, Mifepristone in combination with
      Tamoxifen did not increase prostate cancer cell death compared with their
      individual values. The involvement of the TRAIL pathway was further confirmed by
      the activation of caspase-8 in Mifepristone-treated cells. This was followed by
      truncation of Bid, confirming that Mifepristone activates the TRAIL pathway. This
      knowledge is being used to design a combination treatment of TRAIL and
      Mifepristone to induce significant apoptosis in prostate cancer cells.

PMID- 11585753
TI  - The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling
      and suppresses the growth of HER2-overexpressing tumor cells.
AB  - The epidermal growth factor receptor (EGFR) is commonly overexpressed in many
      human tumors and provides a new target for anticancer drug development. ZD1839
      ("Iressa"), a quinazoline tyrosine kinase inhibitor selective for the EGFR, has
      shown good activity in preclinical studies and in the early phase of clinical
      trials. However, because it remains unclear which tumor types are the best
      targets for treatment with this agent, the molecular characteristics that
      correlate with tumor sensitivity to ZD1839 have been studied. In a panel of human
      breast cancer and other epithelial tumor cell lines, HER2-overexpressing tumors
      were particularly sensitive to ZD1839. Growth inhibition of these tumor cell
      lines was associated with the dephosphorylation of EGFR, HER2, and HER3,
      accompanied by the loss of association of HER3 with phosphatidylinositol 3
      kinase, and down-regulation of Akt activity. These studies suggest that HER2
      overexpressing tumors are particularly susceptible to the inhibition of HER
      family tyrosine kinase signaling and suggest novel strategies to treat these
      particularly aggressive tumors.

PMID- 11585754
TI  - Potent antitumor activity and improved pharmacological profile of ST1481, a novel
      7-substituted camptothecin.
AB  - Relevant drawbacks of the molecular structure and mechanism of the action of
      camptothecins are the instability of the E ring lactone and the reversibility of
      drug-target interaction. Such features are expected to limit the clinical
      efficacy of conventional camptothecins. In an attempt to overcome these
      limitations and to improve the pharmacological profile of camptothecins, a novel
      series of seven modified lipophilic analogues was synthesized based on the
      hypothesis that lipophilicity could promote a rapid cellular accumulation and
      stabilization of drug-target interaction. A novel analogue (ST1481) of the
      series, characterized by a potent antitopoisomerase and cytotoxic activity, was
      selected for preclinical development. A detailed preclinical study of ST1481 was
      performed in the H460 non-small cell lung tumor model using oral administration
      and various treatment schedules. Under all of the conditions, ST1481 exhibited an
      impressive efficacy in terms of tumor growth inhibition (tumor volume inhibition
      percentage > 99%), log(10) cell kill, rate of complete responses (including
      "cures"), and an improvement of the therapeutic index compared with topotecan
      (used as the reference drug). The cytotoxic potency was also reflected by the in
      vivo potency, because the drug activity was observed at doses as low as 0.25
      mg/kg with the daily schedule. In contrast to topotecan, no cross-resistance to
      ST1481 was found in ovarian carcinoma cells overexpressing P-glycoprotein
      (A2780/DX). A similar trend in the improvement of activity was also observed in
      the same tumor model growing in vivo with a 100% rate of complete tumor
      regressions. A rapid intestinal absorption and good oral bioavailability were
      supported by in vivo distribution studies, because the peak values of drug
      accumulation were found from 1 to 2 h after administration. The relevant liver
      accumulation may account for a marked effect of ST1481 against liver metastases
      induced by the ovarian carcinoma IGROV-1. In conclusion, the results support the
      hypothesis that a potent lipophilic camptothecin with a proper substituent at the
      position 7 may have therapeutic advantages likely related to a rapid
      intracellular uptake and tissue distribution, stabilization of the drug-target
      complex, and good oral bioavailability. Overall, the results support the
      preclinical interest of ST1481 in terms of efficacy, potency, toxicity profile,
      and ability to overcome multidrug resistance.

PMID- 11585755
TI  - The characterization of novel, dual ErbB-2/EGFR, tyrosine kinase inhibitors:
      potential therapy for cancer.
AB  - The type I receptor tyrosine kinases constitute a family of transmembrane
      proteins involved in various aspects of cell growth and survival and have been
      implicated in the initiation and progression of several types of human
      malignancies. The best characterized of these proteins are the epidermal growth
      factor receptor (EGFR) and ErbB-2 (HER-2/neu). We have developed potent
      quinazoline and pyrido-[3,4-d]-pyrimidine small molecules that are dual
      inhibitors of ErbB-2 and EGFR. The compounds demonstrate potent in vitro
      inhibition of the ErbB-2 and EGFR kinase domains with IC(50)s <80 nM. Growth of
      ErbB-2- and EGFR-expressing tumor cell lines is inhibited at concentrations <0.5
      microM. Selectivity for tumor cell growth inhibition versus normal human
      fibroblast growth inhibition ranges from 10- to >75-fold. Tumor growth in mouse
      s.c. xenograft models of the BT474 and HN5 cell lines is inhibited in a dose
      responsive manner using oral doses of 10 and 30 mg/kg twice per day. In addition,
      the tested compounds caused a reduction of ErbB-2 and EGFR autophosphorylation in
      tumor fragments from these xenograft models. These data indicate that these
      compounds have potential use as therapy in the broad population of cancer
      patients overexpressing ErbB-2 and/or EGFR.

PMID- 11585756
TI  - Expression of CD26 and its associated dipeptidyl peptidase IV enzyme activity
      enhances sensitivity to doxorubicin-induced cell cycle arrest at the G(2)/M
      checkpoint.
AB  - CD26, a M(r) 110,000 surface-bound ectopeptidase with dipeptidyl peptidase IV
      (DPPIV) activity, has an array of diverse functional properties, with a role in T
      cell physiology and the development of certain human cancers. In this study, we
      report that surface expression of CD26, through its associated DPPIV enzyme
      activity, enhanced sensitivity of Jurkat T-cell transfectants to G(2)-M arrest
      induced by the chemotherapeutic drug, doxorubicin. This was associated with
      disruption of cell cycle-related events, including hyperphosphorylation and
      inhibition of p34(cdc2) kinase activity, phosphorylation of cdc25C, and
      alteration in cyclin B1 expression. In addition, we demonstrate that the addition
      of exogenous soluble DPPIV enhanced sensitivity of lymphoid tumor cell lines to
      doxorubicin, suggesting a potentially useful clinical role for CD26/DPPIV in the
      treatment of selected human hematological malignancies.

PMID- 11585757
TI  - Involvement of Cdc25A phosphatase in Hep3B hepatoma cell growth inhibition
      induced by novel K vitamin analogs.
AB  - We previously found that K vitamin analogues caused cell growth inhibition in
      Hep3B hepatoma cells in vitro, which was associated with their inhibitory effects
      on protein tyrosine-phosphatases. In this study, we show that Cdc25A, a protein
      phosphatase, was inactivated by novel arylating K vitamin analogues. The
      inactivation of Cdc25A correlated with their effects on cell growth inhibition.
      Cyclin-dependent kinase (Cdk) 4, an important regulator for G(1) progression, was
      found to be tyrosine-phosphorylated by the arylating analogues, and this
      phosphorylation was correlated with the inhibitory effects of the analogues on
      Cdc25A activity. Furthermore, Cdk4 dephosphorylation experiments showed that
      Compound (Cpd) 5, a prototype arylating analogue, inhibited Cdc25A-mediated Cdk4
      dephosphorylation, whereas Cpd 26, a nonarylating vitamin K analogue, had no
      effect on this event. We also examined Cdk4 kinase activity using retinoblastoma
      protein as a substrate and found that Cpd 5 inhibited retinoblastoma protein
      phosphorylation in a concentration-dependent manner, indicating that Cdk4
      activity was inhibited by Cpd 5 treatment. Moreover, the thiol-antioxidants
      glutathione and N-acetyl-L-cysteine antagonized the Cpd 5-induced Cdk4 tyrosine
      phosphorylation, whereas the nonthiol-antioxidants catalase and superoxide
      dismutase did not. These results suggest that Hep3B cell growth inhibition by
      these K vitamin analogues may be related in part to inactivation of Cdc25A
      activity and support the hypothesis that Cdc25A is an attractive target for drugs
      designed to inhibit cancer cell growth.

PMID- 11585758
TI  - Mechanisms of uptake and resistance to troxacitabine, a novel deoxycytidine
      nucleoside analogue, in human leukemic and solid tumor cell lines.
AB  - Troxacitabine (Troxatyl; BCH-4556; (-)-2'-deoxy-3'-oxacytidine), a deoxycytidine
      analogue with an unusual dioxolane structure and nonnatural L-configuration, has
      potent antitumor activity in animal models and is in clinical trials against
      human malignancies. The current work was undertaken to identify potential
      biochemical mechanisms of resistance to troxacitabine and to determine whether
      there are differences in resistance mechanisms between troxacitabine,
      gemcitabine, and cytarabine in human leukemic and solid tumor cell lines. The
      CCRF-CEM leukemia cell line was highly sensitive to the antiproliferative effects
      of troxacitabine, gemcitabine, and cytarabine with inhibition of proliferation by
      50% observed at 160, 20, and 10 nM, respectively, whereas a deoxycytidine kinase
      (dCK)-deficient variant (CEM/dCK(-)) was resistant to all three drugs. In
      contrast, a nucleoside transport-deficient variant (CEM/ARAC8C) exhibited high
      levels of resistance to cytarabine (1150-fold) and gemcitabine (432-fold) but
      only minimal resistance to troxacitabine (7-fold). Analysis of troxacitabine
      transportability by the five molecularly characterized human nucleoside
      transporters [human equilibrative nucleoside transporters 1 and 2, human
      concentrative nucleoside transporter (hCNT) 1, hCNT2, and hCNT3] revealed that
      short- and long-term uptake of 10-30 microM [(3)H]troxacitabine was low and
      unaffected by the presence of either nucleoside transport inhibitors or high
      concentrations of nonradioactive troxacitabine. These results, which suggested
      that the major route of cellular uptake of troxacitabine was passive diffusion,
      demonstrated that deficiencies in nucleoside transport were unlikely to impart
      resistance to troxacitabine. A troxacitabine-resistant prostate cancer subline
      (DU145(R); 6300-fold) that exhibited reduced uptake of troxacitabine was cross
      resistant to both gemcitabine (350-fold) and cytarabine (300-fold). dCK activity
      toward deoxycytidine in DU145(R) cell lysates was <20% of that in DU145 cell
      lysates, and no activity was detected toward troxacitabine. Sequence analysis of
      cDNAs encoding dCK revealed a mutation of a highly conserved amino acid (Trp(92)-
      >Leu) in DU145(R) dCK, providing a possible explanation for the reduced
      phosphorylation of troxacitabine in DU145(R) lysates. Reduced deamination of
      deoxycytidine was also observed in DU145(R) relative to DU145 cells, and this may
      have contributed to the overall resistance phenotype. These results, which
      demonstrated a different resistance profile for troxacitabine, gemcitabine, and
      cytarabine, suggest that troxacitabine may have an advantage over gemcitabine and
      cytarabine in human malignancies that lack or have low nucleoside transport
      activities.

PMID- 11585759
TI  - Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP)
      3 and MRP1: effect of polyglutamylation on MTX transport.
AB  - We have recently determined that human multidrug resistance protein (MRP) 3,
      which confers resistance to certain natural product agents and methotrexate
      (MTX), is competent in the MgATP-energized transport of MTX and the monoanionic
      bile constituent glycocholate as well as several glutathione and glucuronate
      conjugates. Of these capabilities, the facility of MRP3 in conferring resistance
      to and mediating the transport of MTX is of particular interest because it raises
      the possibility that this pump is a component of the previously described
      cellular efflux system for this antimetabolite. However, if this is to be the
      case, a critical property of cellular MTX efflux that must be addressed is its
      ability to mediate the export of MTX but not that of its intracellular
      polyglutamylated derivatives. Here we examine the role of MRP3 in these and
      related processes by determining the selectivity of this transporter for MTX, MTX
      polyglutamates, and physiological folates. In so doing, we show that MRP3 is not
      only active in the transport of MTX but is also active in the transport the
      physiological folates folic acid (FA) and N(5)-formyltetrahydrofolic acid
      (leucovorin) and that polyglutamylation of MTX abolishes transport. Both FA and
      leucovorin are subject to high-capacity (V(max(FA)), 1.71 +/- 0.05 nmol/mg/min;
      V(max(leucovorin)), 3.63 +/- 1.20 nmol/mg/min), low-affinity (K(m(FA)), 1.96 +/-
      0.13 mM; K(m(leucovorin)), 1.74 +/- 0.65 mM) transport by MRP3. Addition of a
      single glutamyl residue to MTX is sufficient to diminish transport by >95%. We
      also show that polyglutamylation similarly affects the capacity of MRP1 to
      transport MTX and that physiological folates are also subject to MgATP-stimulated
      transport by MRP1. On the basis of the capacity to transport MTX but not MTX
      Glu(2), it is concluded that MRP3 and MRP1 represent components of the previously
      described cellular efflux system for MTX. The capacity of MRP3 to transport
      folates indicates that it may reduce intracellular levels of these compounds and
      thereby indirectly influence antifolate cytotoxicity, and it also implies that
      this pump may play a role in the response to chemotherapeutic regimens in which
      leucovorin is a component.

PMID- 11585760
TI  - Absence of the wild-type allele predicts poor prognosis in adult de novo acute
      myeloid leukemia with normal cytogenetics and the internal tandem duplication of
      FLT3: a cancer and leukemia group B study.
AB  - The FLT3 gene is mutated by an internal tandem duplication (ITD) in 20-25% of
      adults with acute myeloid leukemia (AML). We studied 82 adults <60 years of age
      with primary AML and normal cytogenetics, who received uniform high-dose therapy
      and found FLT3 ITD in 23 (28%) patients. When the 23 FLT3 ITD+ cases were
      compared with the 59 cases with wild-type (WT) FLT3, disease-free survival (DFS)
      was inferior (P = 0.03), yet overall survival (OS) was not different (P = 0.14).
      However, 8 (35%) of 23 FLT3 ITD/+ cases also lacked a FLT3 WT allele (FLT3(ITD
      R)) as determined by PCR and loss of heterozygosity. Thus, three genotypic groups
      were identified: normal FLT3(WT/WT), heterozygous FLT3(ITD/WT), and hemizygous
      FLT3(ITD/-). DFS and OS were significantly inferior for patients with FLT3(ITD/-)
      (P = 0.0017 and P = 0.0014, respectively). Although DFS and OS for FLT3(WT/WT)
      and FLT3(ITD/WT) groups did not differ (P = 0.32 and P = 0.98, respectively), OS
      of the FLT3(ITD/-) group was worse than the FLT3(WT/WT) (P = 0.0005) and
      FLT3(ITD/WT) (P = 0.008) groups. We propose a model in which FLT3(ITD/-)
      represents a dominant positive, gain-of-function mutation providing AML cells
      with a greater growth advantage compared with cells having the FLT3(WT/WT) or
      FLT3(ITD/WT) genotypes. In conclusion, we have identified the FLT3(ITD/-)
      genotype as an adverse prognostic factor in de novo AML with normal cytogenetics.
      A poor prognosis of the relatively young FLT3(ITD/-) adults (median age, 37
      years), despite treatment with current dose-intensive regimens, suggests that new
      treatment modalities, such as therapy with a FLT3 tyrosine kinase inhibitor, are
      clearly needed for this group of patients.

PMID- 11585761
TI  - Macrophages orchestrate the immune response to tumor cell death.
AB  - The mechanisms by which the immune system distinguishes normal developmental cell
      death from pathological immunogenic cell killing are central to effective cancer
      immunotherapy. Using HSVtk suicide gene therapy, we showed that macrophages can
      distinguish between tumor cells dying through classical apoptosis and tumor cells
      engineered to die through nonapoptotic mechanisms, resulting in secretion of
      either immunosuppressive cytokines (interleukin 10 and transforming growth factor
      beta) or inflammatory cytokines (tumor necrosis factor alpha or interleukin
      1beta), respectively. Additionally heat shock protein 70 acts as one component of
      a bimodal alarm signal that activates macrophages in the presence of stressful,
      immunogenic tumor cell killing. These differential responses of macrophages can
      also be used to vaccinate mice against tumor challenge, using adoptive transfer,
      as well as to cure mice of established tumors.

PMID- 11585762
TI  - Biochemical genetic analysis of indanocine resistance in human leukemia.
AB  - Indanocine is a potent tubulin-binding drug that is cytotoxic to multidrug
      resistant cancer cell lines. We demonstrated that indanocine specifically induces
      apoptosis in malignant B cells from patients with chronic lymphocytic leukemia.
      To address the exact biochemical basis for indanocine toxicity, an indanocine
      resistant clone was selected from mutagenized CEM human lymphoblastoid cells. The
      resistant cells displayed a stable indanocine-resistant phenotype for at least 9
      months in drug-free culture. The cloned cells are cross-resistant to colchicine
      and vinblastine, but not to paclitaxel, and do not have increased expression of
      the multidrug-resistant p170 glycoprotein. In both parental cells and cell
      extracts, indanocine treatment caused tubulin depolymerization. In contrast, the
      tubulin in the resistant clone did not depolymerize under identical conditions.
      Both extract mixing and cell fusion experiments suggested that a stable
      structural change in microtubules, rather than a soluble factor, was responsible
      for indanocine resistance. Sequence analysis of parental and resistant cells
      revealed a single point mutation in the M40 isotype of beta-tubulin at nucleotide
      1050 (G-->T, Lys(350)-->Asn) in the indanocine-resistant clone, in a region close
      to the putative colchicine binding site.

PMID- 11585763
TI  - Par-4 drives trafficking and activation of Fas and Fasl to induce prostate cancer
      cell apoptosis and tumor regression.
AB  - Prostate cancer cells are generally resistant to apoptosis by conventional
      therapy. During a search for molecules that may overcome prostate cancer cell
      survival mechanisms, we identified the prostate apoptosis response-4 (Par-4)
      gene. Par-4 induced apoptosis of selective prostate cancer cells PC-3, DU-145,
      and TSU-Pr and caused tumor regression by inhibition of NF-kappaB activity and
      cell membrane trafficking of Fas and FasL that leads to the activation of the Fas
      Fas-associated death domain-caspase-8 pro-death pathway. Neither Fas pathway
      activation alone nor inhibition of NF-kappaB activity with IkappaB-super
      repressor was sufficient to induce apoptosis of prostate cancer cells.
      Coregulation of these two pathways was essential and sufficient for Par-4 to
      induce apoptosis. On the other hand, prostate cancer cells LNCaP or normal
      prostatic epithelial cells that were resistant to apoptosis by Par-4 did not show
      Fas or FasL trafficking. These findings identify a mechanism of apoptosis by Par
      4 and suggest that Par-4 may have therapeutic potential.

PMID- 11585764
TI  - Second primary or recurrence? Comparative patterns of p53 and K-ras mutations
      suggest that serous borderline ovarian tumors and subsequent serous carcinomas
      are unrelated tumors.
AB  - The role of serous borderline ovarian tumors (BOTs) in the pathogenesis of serous
      ovarian carcinomas is unclear. Some authors have compared mutations in serous
      BOTs to those in serous ovarian carcinomas, but the data on two common oncogenes,
      p53 and K-ras, remain inconclusive. To further clarify the relationship between
      the two tumors, we performed mutational analysis on tumors from a set of eight
      patients who first presented with advanced-stage serous BOTs and later developed
      grade 1 serous carcinomas. Epithelium from eight advanced-stage serous BOTs and
      subsequent grade 1 papillary serous carcinomas was microdissected and retrieved
      using a PixCell laser-capture microscope. Stroma was dissected as an internal
      control. The DNA was extracted with proteinase K and analyzed by single-strand
      conformational polymorphism-PCR for p53 and K-ras mutations. Bands with altered
      motility were analyzed by direct cycle sequencing. Seven of eight patients
      demonstrated different mutations in the secondary tumor compared with the primary
      tumor. For three patients, p53 mutations were identified in the BOTs that were
      absent from the carcinomas, suggesting a nonclonal origin for the carcinomas.
      These findings are consistent with the hypothesis that advanced-stage serous BOTs
      represent a distinct pathological entity compared with grade 1 serous epithelial
      ovarian carcinoma.

PMID- 11585765
TI  - Multipoint imprinting analysis indicates a common precursor cell for gonadal and
      nongonadal pediatric germ cell tumors.
AB  - Pediatric germ cell tumors (GCTs) commonly arise at extragonadal sites. It has
      been proposed that nongonadal GCTs arise from ectopic primordial germ cells that
      have aberrantly migrated during embryogenesis. During a time between their
      migration and development to mature gametes, primordial germ cells are
      characterized by their lack of imprinting, which can be assessed by the
      evaluation of allelic gene expression and DNA methylation in differentially
      methylated control regions. To elucidate the cellular origin of nongonadal GCTs,
      we evaluated the imprinting status of 21 gonadal and 21 nongonadal pediatric
      GCTs. Allele-specific H19 and IGF-2 expression was assessed with reverse
      transcription-PCR followed by digestion at polymorphic restriction sites. DNA
      methylation was evaluated after bisulfite modification, PCR amplification, and
      restriction digestion at a consistently methylated CpG dinucleotide within the 5'
      flanking region of the SNRPN gene. These results were compared with genetic gains
      and losses determined by comparative genomic hybridization. Seven of 15
      informative tumors showed biallelic H19 expression, and 8 of 17 informative
      tumors showed biallelic IGF-2 expression. The frequency of biallelic gene
      expression was comparable in gonadal and nongonadal GCTs. Sixteen of 19 gonadal
      GCTs and 17 of 21 nongonadal GCTs showed absence of methylation of SNRPN
      consistent with loss of imprinting. One testicular GCT and three nongonadal GCTs
      showed a somatic methylation pattern. Two ovarian teratomas and one mediastinal
      teratoma showed only methylated SNRPN, consistent with entry into meiosis. Twenty
      one of 22 non-GCT control samples showed a somatic methylation pattern. Gonadal
      and nongonadal germ cell tumors are derived from primordial germ cells that have
      consistently lost the imprinting of SNRPN and partly lost imprinting of H19 and
      IGF-2. Because the imprinting pattern of the latter genes differs from that found
      in testicular GCTs of adult patients, our data suggest that pediatric GCTs arise
      from a different stage of germ cell development.

PMID- 11585766
TI  - Epigenetic inactivation of the RASSF1A 3p21.3 tumor suppressor gene in both clear
      cell and papillary renal cell carcinoma.
AB  - Renal cell carcinoma (RCC), the most common adult kidney neoplasm, is
      histopathologically heterogeneous, with most sporadic RCCs ( approximately 80%)
      classified as clear cell (CC) tumors. Chromosome 3p allele loss is the most
      frequent genetic alteration in RCC but is associated specifically with sporadic
      and hereditary forms of clear cell RCC (CC-RCC) and is not a feature of non-CC
      RCC, such as papillary (chromophilic) RCC. The VHL tumor suppressor gene (TSG)
      maps to chromosome 3p25, and somatic inactivation of the VHL gene occurs in up to
      70% of CC-RCC tumors and cell lines. However, VHL inactivation is not sufficient
      for CC-RCC tumorigenesis, and inactivation of 3p12-p21 TSG(s) appears to be
      necessary in CC-RCC irrespective of VHL gene inactivation status. Recently, we
      demonstrated that the candidate 3p21 TSG, RASSF1A, is hypermethylated in most
      small cell lung cancers. We have now investigated the role of RASSF1A
      inactivation in primary RCC tumors. RASSF1A promoter methylation was detected in
      23% (32 of 138) of primary CC-RCC tumors. In CC-RCC cell lines, RASSF1A
      methylation was associated with silencing of RASSF1A expression and restoration
      of expression after treatment with 5'-azacytidine. The frequency of RASSF1A
      methylation was similar in CC-RCC with and without VHL gene inactivation (24%
      versus 21%), and there was no association between epigenetic silencing of the
      RASSF1A and VHL TSGs, because 0 of 6 tumors with VHL hypermethylation had RASSF1A
      methylation, and VHL was not methylated in 26 CC-RCCs with RASSF1A methylation.
      Although 3p allele loss has been reported rarely in papillary RCC, we identified
      RASSF1A methylation in 44% (12 of 27) of papillary RCCs analyzed. Thus: (a)
      inactivation of RASSF1A is a frequent event in both CC-RCC and papillary RCC
      tumors; (b) there is no relationship between epigenetic silencing of RASSF1A and
      VHL inactivation status in CC-RCC. Fifty-four CC-RCCs analyzed for RASSF1A
      methylation were informative for 3p21 allele loss, and 20% (7 of 35) with 3p21
      allele loss demonstrated RASSF1A methylation. All informative CC-RCCs with 3p21
      allele loss and no RASSF1A methylation also demonstrated allele losses at other
      regions of 3p so that tumorigenesis in these cases may result from: (a)
      haploinsufficiency of RASSF1A; (b) inactivation of other 3p21 TSGs; or (c)
      inactivation of 3p TSGs from outside of 3p21. RASSF1A is the first TSG to be
      inactivated frequently in both papillary and CC-RCCs. The finding of frequent
      epigenetic inactivation of RASSF1A in papillary RCCs despite previous studies
      reporting infrequent 3p21 allele loss in this tumor type illustrates how the
      systematic identification of all major human cancer genes will require detailed
      analysis of the cancer genome and epigenome.

PMID- 11585767
TI  - Modulation of angiogenesis and tumorigenicity of human melanocytic cells by
      vascular endothelial growth factor and basic fibroblast growth factor.
AB  - Human melanoma cells express two prominent angiogenic factors, e.g., vascular
      endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF/fibroblast growth factor-2). In this study, we report on the relative
      contribution of these two factors to in vitro and in vivo growth of a tumorigenic
      melanoma cell line (WM164) and nontumorigenic, immortalized melanocytes
      (FM516SV). Overexpression of either cytokine significantly boosted tumorigenicity
      of WM164 cells in immunodeficient SCID mice. Attempting to overexpress bFGF
      antisense sequences produced no viable clones confirming earlier reports that
      autocrine bFGF is obligatory to melanoma cell survival and growth. By contrast,
      down-regulation of endogenous VEGF production did not affect growth of WM164
      cells in vitro. In vivo expansion of WM164 cells expressing VEGF antisense was
      delayed but not abrogated. Forced expression of either bFGF or VEGF in
      immortalized but nontumorigenic melanocytes did not induce sustained tumor growth
      in vivo highlighting that neither of the two factors is sufficient for induction
      of tumorigenicity in this model system. Overexpression of either cytokine in
      WM164 cells led to the development of atypical large vessels but not to an
      increase in microvessel density. Taken together our results confirm an essential
      autocrine role of bFGF in human melanoma and indicate a beneficial but
      nonessential role of VEGF in the tumorigenic phenotype of human melanoma cells.

PMID- 11585768
TI  - Dynamics of notch expression during murine prostate development and
      tumorigenesis.
AB  - Notch signaling has been widely demonstrated to be responsible for cell fate
      determination during normal development and implicated in human T-cell leukemia
      and mouse mammary carcinomas. Here we show that Notch signaling may be involved
      in prostatic development and cancer cell growth. In situ hybridization and
      reverse transcription-PCR analyses revealed that Notch1 was expressed in prostate
      epithelial cells during normal development and in prostate cancer cells.
      Characterization of Notch1-green fluorescent protein transgenic mice, in which
      the expression of reporter green fluorescent protein is under the control of the
      Notch1 promoter, indicated that Notch1-expressing cells were associated with the
      basal epithelial cell population in the prostate. Examination of the transgenic
      adenocarcinoma of the mouse prostate showed that expression of Notch1 was
      elevated in malignant prostatic epithelial cells of primary and metastatic
      tumors. Expression of Notch ligands, however, was low or undetectable in cultured
      prostate cancer cells or in malignant prostatic epithelial cells in transgenic
      adenocarcinoma of the mouse prostate. Furthermore, overexpression of a
      constitutively active form of Notch1 inhibited the proliferation of various
      prostate cancer cells, including DU145, LNCaP, and PC3 cells. Taken together, our
      data indicate for the first time that Notch signaling may play a role in murine
      prostatic development and tumorigenesis.

PMID- 11585769
TI  - Generation of multiple angiogenesis inhibitors by human pancreatic cancer.
AB  - A primary inoculum of human pancreatic cancer cells (BxPC-3) has the ability to
      inhibit the growth of a secondary tumor in an in vivo animal model. Such ability
      suggests that the primary tumor is producing inhibitors that act at the site of
      the secondary tumor. Accordingly we attempted to discover which inhibitors are
      produced by pancreatic cancer cells. We determined that pancreatic cancer cells
      process angiostatin isoforms from plasminogen. Additionally, we isolated and
      characterized an uncleaved "latent" antiangiogenic antithrombin (aaAT) molecule
      processed from systemically available AT by pancreatic cancer cells as well as a
      cleaved form of aaAT processed from systemically available AT by pancreatic
      cancer cells. Human AT, cleaved with human neutrophil elastase, inhibits
      angiogenesis in the chorioallantoic membrane assay. This human aaAT molecule is
      able to inhibit the growth of pancreatic tumors in immune-compromised mice. Our
      work represents the first demonstration of multiple angiogenesis inhibitors from
      a single tumor and suggests that antiangiogenic therapies may provide an avenue
      for future treatment of pancreatic cancer.

PMID- 11585770
TI  - Expression of cyclooxygenase-2 and inducible nitric oxide synthase in human
      ovarian tumors and tumor-associated macrophages.
AB  - This study investigates whether and to what extent cyclooxygenase type-2 (COX-2)
      and inducible nitric oxide-synthase (iNOS), both known to have an
      immunosuppressive effect, are expressed in human ovarian tumors. Because COX-2
      and iNOS can be expressed by activated macrophages, the presence of tumor
      associated macrophages and the expression of COX-2 and iNOS by these tumor
      associated macrophages were determined. The results obtained may provide insight
      into the function of COX-2 and iNOS expression by tumors. The expression of COX-2
      and iNOS in tumor cells and macrophages was assessed in 18 malignant, 15
      borderline, and 14 benign human ovarian tumors by immunohistochemical staining of
      frozen tissue sections. The intra- and peritumoral macrophages were stained using
      an anti-CD68 monoclonal antibody. Most of the malignant tumors (15 of 18), 10 of
      15 borderline, and 9 of 14 benign tumors showed COX-2 expression in the
      epithelial cells, a result which indicates that COX-2 expression is not exclusive
      to malignancy. In addition, COX-2 staining was more intense in the epithelial
      cells of benign and borderline tumors than in malignant tumors. Weak iNOS
      staining was observed in 5 of 18 malignant, 4 of 15 borderline, and 5 of 14
      benign tumors. The number of tumor-associated macrophages varied widely between
      the different tumors. The highest number of tumor-associated macrophages (> or
      =20/0.125 mm(2)) was observed in malignant tumors, whereas low to moderate intra-
      and peritumoral macrophage infiltration (5-20/0.125 mm(2)) was observed in the
      borderline and benign tumors. COX-2-positive tumor-associated macrophages were
      found in 3 of 18 malignant tumors, 7 of 15 borderline tumors, and 1 of 14 benign
      tumors. The number of COX-2-positive tumor-associated macrophages ranged from 3
      to 30% of the total macrophage population. Some malignant (4 of 18), borderline
      (5 of 15), and benign (2 of 14) tumors contained iNOS-positive macrophages.
      Notable was that COX-2- and iNOS-positive macrophages were predominantly located
      in the tumor stroma, the regions between tumor and stroma, and in the lumina of
      the tumor when located in the tumor tissue. These data indicate that not only
      malignant but also borderline and benign ovarian tumors can exhibit increased
      levels of COX-2 and iNOS expression. In addition, a small proportion of the tumor
      associated macrophages found in malignant, borderline, and benign tumors seems to
      be in an activated state, judged by their iNOS and COX-2 expression. This
      subpopulation of tumor-associated macrophages was invariably located in the tumor
      stroma or in the lumina of the tumor, specifically suggesting that macrophages
      outside the tumor can be tumor cytotoxic.

PMID- 11585771
TI  - Androgen receptor mediates the reduced tumor growth, enhanced androgen
      responsiveness, and selected target gene transactivation in a human prostate
      cancer cell line.
AB  - The growth and development of the prostate gland are regulated by the androgen
      and the androgen receptor (AR). Despite our molecular understanding of the roles
      of the AR regulating; a downstream target gene transcription, the direct or
      indirect (stromally mediated) actions of the androgen in controlling prostate
      cell growth and differentiation are still unclear. In this report, an invasive;
      and metastatic human prostate tumor cell line, androgen-repressed human prostate
      cancer cell line (ARCaP), either transduced with wild-type human AR (hAR) or a
      control neomycin-resistant plasmid DNA, was used to evaluate the direct role of
      AR in regulating prostate tumor cell growth and gene transcription. Results
      showed that: (a) introduction of wild-type hAR to ARCaP cells restored positive
      androgen regulation of prostate tumor cell growth in vitro through an enhanced
      cell-cycle progression from G(0)/G(1) to S and G(2)-M phases; (b) hAR was shown
      to transactivate glucocorticoid-responsive element but not prostate-specific
      antigen promoter-directed reporter gene expression; and (c) hAR-transduced ARCaP
      cells exhibited reduced growth, invasion, and migratory behavior in vitro and
      tumor growth in vivo. These results suggest that the introduction of hAR into the
      invasive human prostate cancer ARCaP cell line restored its androgen-regulated
      cell growth, decreased the rate of tumor growth, and selectively activated AR
      target gene expression. These cellular functions in response to androgen are
      commonly associated with increased differentiation of prostate epithelial cells.

PMID- 11585772
TI  - Insulin-like growth factor-1 induces survival and growth of biologically early
      melanoma cells through both the mitogen-activated protein kinase and beta-catenin
      pathways.
AB  - Melanoma cells produce growth factors for autocrine growth control and for
      stimulating fibroblasts and endothelial cells in the tumor stroma. Activated
      stromal fibroblasts can in turn secrete growth factors that support tumor growth.
      We studied this feedback from fibroblasts to melanoma cells by overexpressing
      insulin-like growth factor 1 (IGF-1) with an adenoviral vector. Melanoma cells do
      not produce IGF-1. IGF-1 enhanced survival, migration, and growth of cells from
      biologically early lesions, but not from biologically late primary or metastatic
      lesions. Early melanoma cells were activated by IGF-1 to phosphorylate Erk1 and 
      2 of the mitogen-activated protein kinase pathway. IGF-1 also activated Akt,
      inhibited its down-stream effector GSK3-beta, and stabilized beta-catenin. Late
      primary and metastatic melanoma cells did not respond to growth stimulation by
      IGF-1 because of a constitutive activation of the mitogen-activated protein
      kinase pathway and a higher level of stabilized beta-catenin. These studies
      demonstrate that fibroblast-derived growth factors from the tumor environment can
      provide the malignant cells with a positive feedback through multiple mechanisms
      but that this stimulation is required only for cells from early and not late
      stages of tumor progression.

PMID- 11585773
TI  - Cables enhances cdk2 tyrosine 15 phosphorylation by Wee1, inhibits cell growth,
      and is lost in many human colon and squamous cancers.
AB  - Cyclin-dependent kinase 2 (cdk2) is a small serine/threonine kinase that
      regulates cell cycle progression. Cdk2 activity is tightly controlled by several
      mechanisms, including phosphorylation and dephosphorylation events. Cables is a
      recently described novel cdk-interacting protein. In proliferating cells, Cables
      was predominantly localized in the nucleus by cell fractionation and
      immunostaining. Expression of Cables in HeLa cells inhibited cell growth and
      colony formation. Cables enhanced cdk2 tyrosine 15 phosphorylation by the Wee1
      protein kinase, an inhibitory phosphorylation, which led to decreased cdk2 kinase
      activity. The gene encoding Cables is located on human chromosome 18q11-12, a
      site that is frequently lost in squamous, colon, and pancreas cancers. We found
      that Cables was strongly expressed in normal human epithelial cells including
      squamous and glandular mucosa. Breast and pancreatic cancers show strong Cables
      expression; however, loss of Cables expression was found in approximately 50-60%
      of primary colon and head and neck cancer specimens. Lack of Cables expression
      was associated with loss of heterozygosity on chromosome 18q11. The data provide
      evidence for a Cables-mediated interplay between cdk2 and Wee1 that leads to
      inhibition of cell growth. Conversely, loss of Cables may cause uncontrolled cell
      growth and enhance tumor formation.

PMID- 11585774
TI  - Thioredoxin expression in primary T-cell acute lymphoblastic leukemia and its
      therapeutic implication.
AB  - Increased expression of intracellular thioredoxin has been implicated in the
      inhibition of apoptosis and in a decrease in the sensitivity of the malignancies
      to drug-induced apoptosis. In the present studies, we analyzed expression of
      thioredoxin in samples from 28 children with T-cell acute lymphoblastic leukemia
      and analyzed their sensitivity toward inhibition of thioredoxin expression.
      Thioredoxin was expressed in variable amounts. Higher expression was associated
      with higher WBC counts. Exogenously added thioredoxin stimulated proliferation of
      clonogenic cells among the T-cell acute lymphoblastic leukemia samples expressing
      relatively lower levels of intracellular thioredoxin, whereas there was no effect
      on the clonogenic cells expressing high levels of thioredoxin. In addition, there
      was differential sensitivity of the leukemia clonogenic cells toward 1
      methylpropyl 2-imidazolyl disulfide, an inhibitor of thioredoxin expression, as
      compared with normal hematopoietic progenitors. This suggests the possibility of
      using this approach for treatment. Because overexpression of thioredoxin is
      associated with resistance to many anticancer drugs, the inhibition of
      thioredoxin expression may overcome this drug resistance and probably sensitize
      leukemia cells to other chemotherapeutic agents.

PMID- 11585775
TI  - Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of
      human melanoma is regulated by smac/DIABLO release from mitochondria.
AB  - In previous studies we have shown that the sensitivity of melanoma cell lines to
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis
      was determined largely by the level of expression of death receptor TRAIL
      receptor 2 on the cells. However, approximately one-third of melanoma cell lines
      were resistant to TRAIL, despite expression of high levels of TRAIL receptor 2.
      The present studies show that these cell lines had similar levels of TRAIL
      induced activated caspase-3 as the TRAIL-sensitive lines, but the activated
      caspase-3 did not degrade substrates downstream of caspase-3 [inhibitor of
      caspase-activated DNase and poly(ADP-ribose) polymerase]. This appeared to be due
      to inhibition of caspase-3 by X-linked inhibitor of apoptosis (XIAP) because XIAP
      was bound to activated caspase-3, and transfection of XIAP into TRAIL-sensitive
      cell lines resulted in similar inhibition of TRAIL-induced apoptosis. Conversely,
      reduction of XIAP levels by overexpression of Smac/DIABLO in the TRAIL-resistant
      melanoma cells was associated with the appearance of catalytic activity by
      caspase-3 and increased TRAIL-induced apoptosis. TRAIL was shown to cause release
      of Smac/DIABLO from mitochondria, but this release was greater in TRAIL-sensitive
      cell lines than in TRAIL-resistant cell lines and was associated with down
      regulation of XIAP levels. Furthermore, inhibition of Smac/DIABLO release by
      overexpression of Bcl-2 inhibited down-regulation of XIAP levels. These results
      suggest that Smac/DIABLO release from mitochondria and its binding to XIAP are an
      alternative pathway by which TRAIL induces apoptosis of melanoma, and this
      pathway is dependent on the release of activated caspase-3 from inhibition by
      XIAP and possibly other inhibitor of apoptosis family members.

PMID- 11585776
TI  - Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible
      factor (HIF)-1alpha, HIF-2alpha, and vascular endothelial growth factor
      expression and their regulation by the phosphatidylinositol 3'-kinase/Akt
      signaling pathway.
AB  - Many oncogenes induce expression of vascular endothelial growth factor (VEGF), a
      key factor in tumor angiogenesis. Phosphatidylinositol 3'-kinase (PI3K)/Akt is a
      common signaling pathway for oncogenes and tumor suppressor genes and is involved
      in VEGF regulation. Because hypoxia is a major stimulus for VEGF production, we
      examined the effects of LY294002, a selective PI3K inhibitor, on hypoxia
      inducible factor (HIF)-1alpha and HIF-2alpha expression and on endogenous VEGF
      responses to hypoxia. A panel of breast cancer cell lines reflecting the
      different genetic changes occurring in human breast cancer was analyzed. LY294002
      inhibited HIF-1alpha induction and phosphorylation under hypoxia. However, HIF
      2alpha expression was not affected. Basal and hypoxia-inducible VEGF expression
      was reduced at both mRNA and protein levels by 50%. V12-ras overexpression
      resulted in an increase in hypoxia-induced HIF-1alpha and HIF-2alpha expression.
      This effect was blocked by PI3K inhibitor, demonstrating one mechanism for ras
      synergy with hypoxia-mediated induction of genes. The decreased HIF-1alpha
      expression was not dependent on VHL interaction because a renal carcinoma cell
      line with VHL mutation and constitutive high HIF-1alpha expression also showed
      down-regulation of HIF-1alpha after treatment with LY294002. These results have
      implications for the use of PI3K inhibitors to inhibit synergistic effects of
      hypoxia with a wide range of common oncogenes.

PMID- 11585777
TI  - Expression of the antiangiogenic factor 16K hPRL in human HCT116 colon cancer
      cells inhibits tumor growth in Rag1(-/-) mice.
AB  - The M(r) 16,000 NH(2)-terminal fragment of human prolactin (16K hPRL) is a potent
      antiangiogenic factor inhibiting endothelial cell function in vitro and
      neovascularization in vivo. The present study was undertaken to test the ability
      of 16K hPRL to inhibit the growth of human HCT116 colon cancer cells transplanted
      s.c. into Rag1(-/-) mice. For this purpose, HCT116 cells were stably transfected
      with an expression vector encoding a peptide that included the signal peptide and
      first 139 amino acid residues of human prolactin (HCT116(16K)). Stable clones of
      HCT116(16K) cells secreted large amounts of biologically active 16K hPRL into the
      culture medium. Growth of HCT116(16K) cells in vitro was not different from wild
      type HCT116 (HCT116(wt)) or vector-transfected HCT116 (HCT116(vector)) cells.
      Addition of recombinant 16K hPRL had no effect on the proliferation of HCT116(wt)
      cells in vitro. Tumor growth of HCT116(16K) cells implanted into Rag1(-/-) mice
      was inhibited 63% in four separate experiments compared with tumors formed from
      HCT116(wt) or HCT116(vector) cells. Inhibition of tumor growth of HCT116(16K)
      cells was correlated with a decrease in microvascular density by 44%. These data
      demonstrate that biologically active 16K hPRL can be expressed and secreted from
      human colon cancer cells using a gene transfer approach and that production of
      16K hPRL by these cells was capable of inhibiting tumor growth and
      neovascularization. These findings support the potential of 16K hPRL as a
      therapeutic agent for the treatment of colorectal cancer.

PMID- 11585778
TI  - Re: Akasaka, H., et al., Molecular anatomy of BCL6 translocations revealed by
      long-distance polymerase chain reaction-based assays. Cancer Res., 60: 2335-2341,
      2000.

PMID- 11585780
TI  - Laboratory-acquired parasitic infections from accidental exposures.
AB  - Parasitic diseases are receiving increasing attention in developed countries in
      part because of their importance in travelers, immigrants, and immunocompromised
      persons. The main purpose of this review is to educate laboratorians, the primary
      readership, and health care workers, the secondary readership, about the
      potential hazards of handling specimens that contain viable parasites and about
      the diseases that can result. This is accomplished partly through discussion of
      the occupationally acquired cases of parasitic infections that have been
      reported, focusing for each case on the type of accident that resulted in
      infection, the length of the incubation period, the clinical manifestations that
      developed, and the means by which infection was detected. The article focuses on
      the cases of infection with the protozoa that cause leishmaniasis, malaria,
      toxoplasmosis, Chagas' disease (American trypanosomiasis), and African
      trypanosomiasis. Data about 164 such cases are discussed, as are data about cases
      caused by intestinal protozoa and by helminths. Of the 105 case-patients infected
      with blood and tissue protozoa who either recalled an accident or for whom the
      likely route of transmission could be presumed, 47 (44.8%) had percutaneous
      exposure via a contaminated needle or other sharp object. Some accidents were
      directly linked to poor laboratory practices (e.g., recapping a needle or working
      barehanded). To decrease the likelihood of accidental exposures, persons who
      could be exposed to pathogenic parasites must be thoroughly instructed in safety
      precautions before they begin to work and through ongoing training programs.
      Protocols should be provided for handling specimens that could contain viable
      organisms, using protective clothing and equipment, dealing with spills of
      infectious organisms, and responding to accidents. Special care should be
      exercised when using needles and other sharp objects.

PMID- 11585779
TI  - Antifungal susceptibility testing: practical aspects and current challenges.
AB  - Development of standardized antifungal susceptibility testing methods has been
      the focus of intensive research for the last 15 years. Reference methods for
      yeasts (NCCLS M27-A) and molds (M38-P) are now available. The development of
      these methods provides researchers not only with standardized methods for testing
      but also with an understanding of the variables that affect interlaboratory
      reproducibility. With this knowledge, we have now moved into the phase of (i)
      demonstrating the clinical value (or lack thereof) of standardized methods, (ii)
      developing modifications to these reference methods that address specific
      problems, and (iii) developing reliable commercial test kits. Clinically relevant
      testing is now available for selected fungi and drugs: Candida spp. against
      fluconazole, itraconazole, flucytosine, and (perhaps) amphotericin B;
      Cryptococcus neoformans against (perhaps) fluconazole and amphotericin B; and
      Aspergillus spp. against (perhaps) itraconazole. Expanding the range of useful
      testing procedures is the current focus of research in this area.

PMID- 11585782
TI  - Mycolic acid analysis by high-performance liquid chromatography for
      identification of Mycobacterium species.
AB  - Mycobacterium tuberculosis is the etiologic agent of tuberculosis and can be
      accurately detected by laboratories using commercial genetic tests.
      Nontuberculosis mycobacteria (NTM) causing other mycobacterioses can be difficult
      to identify. The identification processes are confounded by an increasing
      diversity of newly characterized NTM species. The ubiquitous nature of NTM,
      combined with their potential to be opportunistic pathogens in immunocompromised
      as well as nonimmunodeficient patients, further complicates the problem of their
      identification. Since clinical case management varies depending on the etiologic
      agent, laboratories must identify the species in a timely manner. However, only a
      few identification methods can detect the species diversity within the
      Mycobacterium genus. Over the last decade, high-performance liquid chromatography
      analysis of the mycolic acids has become an accepted method for identification of
      mycobacteria. In this review, we assess its development and usefulness as an
      identification technique for Mycobacterium species.

PMID- 11585781
TI  - Immune responses in hookworm infections.
AB  - Hookworms infect perhaps one-fifth of the entire human population, yet little is
      known about their interaction with our immune system. The two major species are
      Necator americanus, which is adapted to tropical conditions, and Ancylostoma
      duodenale, which predominates in more temperate zones. While having many common
      features, they also differ in several key aspects of their biology. Host immune
      responses are triggered by larval invasion of the skin, larval migration through
      the circulation and lungs, and worm establishment in the intestine, where adult
      worms feed on blood and mucosa while injecting various molecules that facilitate
      feeding and modulate host protective responses. Despite repeated exposure,
      protective immunity does not seem to develop in humans, so that infections occur
      in all age groups (depending on exposure patterns) and tend to be prolonged.
      Responses to both larval and adult worms have a characteristic T-helper type 2
      profile, with activated mast cells in the gut mucosa, elevated levels of
      circulating immunoglobulin E, and eosinophilia in the peripheral blood and local
      tissues, features also characteristic of type I hypersensitivity reactions. The
      longevity of adult hookworms is determined probably more by parasite genetics
      than by host immunity. However, many of the proteins released by the parasites
      seem to have immunomodulatory activity, presumably for self-protection. Advances
      in molecular biotechnology enable the identification and characterization of
      increasing numbers of these parasite molecules and should enhance our detailed
      understanding of the protective and pathogenetic mechanisms in hookworm
      infections.

PMID- 11585783
TI  - Periodontal disease as a specific, albeit chronic, infection: diagnosis and
      treatment.
AB  - Periodontal disease is perhaps the most common chronic infection in adults.
      Evidence has been accumulating for the past 30 years which indicates that almost
      all forms of periodontal disease are chronic but specific bacterial infections
      due to the overgrowth in the dental plaque of a finite number of mostly anaerobic
      species such as Porphyromonas gingivalis, Bacteroides forsythus, and Treponema
      denticola. The success of traditional debridement procedures and/or antimicrobial
      agents in improving periodontal health can be associated with the reduction in
      levels of these anaerobes in the dental plaque. These findings suggest that
      patients and clinicians have a choice in the treatment of this overgrowth, either
      a debridement and surgery approach or a debridement and antimicrobial treatment
      approach. However, the antimicrobial approach, while supported by a wealth of
      scientific evidence, goes contrary to centuries of dental teaching that states
      that periodontal disease results from a "dirty mouth." If periodontal disease is
      demonstrated to be a risk factor for cardiovascular disease and stroke, it will
      be a modifiable risk factor since periodontal disease can be prevented and
      treated. Since the antimicrobial approach may be as effective as a surgical
      approach in the restoration and maintenance of a periodontally healthy dentition,
      this would give a cardiac or stroke patient and his or her physician a choice in
      the implementation of treatment seeking to improve the patient's periodontal
      condition so as to reduce and/or delay future cardiovascular events.

PMID- 11585786
TI  - Pathogenesis of cerebral malaria: recent experimental data and possible
      applications for humans.
AB  - Malaria still is a major public health problem, partly because the pathogenesis
      of its major complication, cerebral malaria, remains incompletely understood.
      Experimental models represent useful tools to better understand the mechanisms of
      this syndrome. Here, data generated by several models are reviewed both in vivo
      and in vitro; we propose that some pathogenic mechanisms, drawn from data
      obtained from experiments in a mouse model, may be instrumental in humans. In
      particular, tumor necrosis factor (TNF) receptor 2 is involved in this syndrome,
      implying that the transmembrane form of TNF may be more important than the
      soluble form of the cytokine. It has also been shown that in addition to
      differences in immune responsiveness between genetically resistant and
      susceptible mice, there are marked differences at the level of the target cell of
      the lesion, namely, the brain endothelial cell. In murine cerebral malaria, a
      paradoxical role of platelets has been proposed. Indeed, platelets appear to be
      pathogenic rather than protective in inflammatory conditions because they can
      potentiate the deleterious effects of TNF. More recently, it has been shown that
      interactions among platelets, leukocytes, and endothelial cells have phenotypic
      and functional consequences for the endothelial cells. A better understanding of
      these complex interactions leading to vascular injury will help improve the
      outcome of cerebral malaria.

PMID- 11585784
TI  - Contribution of immune activation to the pathogenesis and transmission of human
      immunodeficiency virus type 1 infection.
AB  - The life cycle of human immunodeficiency virus type 1 (HIV-1) is intricately
      related to the activation state of the host cells supporting viral replication.
      Although cellular activation is essential to mount an effective host immune
      response to invading pathogens, paradoxically the marked systemic immune
      activation that accompanies HIV-1 infection in vivo may play an important role in
      sustaining phenomenal rates of HIV-1 replication in infected persons. Moreover,
      by inducing CD4+ cell loss by apoptosis, immune activation may further be central
      to the increased rate of CD4+ cell turnover and eventual development of CD4+
      lymphocytopenia. In addition to HIV-1-induced immune activation, exogenous immune
      stimuli such as opportunistic infections may further impact the rate of HIV-1
      replication systemically or at localized anatomical sites. Such stimuli may also
      lead to genotypic and phenotypic changes in the virus pool. Together, these
      various immunological effects on the biology of HIV-1 may potentially enhance
      disease progression in HIV-infected persons and may ultimately outweigh the
      beneficial aspects of antiviral immune responses. This may be particularly
      important for those living in developing countries, where there is little or no
      access to antiretroviral drugs and where frequent exposure to pathogenic
      organisms sustains a chronically heightened state of immune activation. Moreover,
      immune activation associated with sexually transmitted diseases,
      chorioamnionitis, and mastitis may have important local effects on HIV-1
      replication that may increase the risk of sexual or mother-to-child transmission
      of HIV-1. The aim of this paper is to provide a broad review of the
      interrelationship between immune activation and the immunopathogenesis,
      transmission, progression, and treatment of HIV-1 infection in vivo.

PMID- 11585787
TI  - Molecular machinations: chemokine signals in host-pathogen interactions.
AB  - Chemokines and their G-protein-coupled receptors represent an ancient and complex
      system of cellular communication participating in growth, development,
      homeostasis and immunity. Chemokine production has been detected in virtually
      every microbial infection examined; however, the precise role of chemokines is
      still far from clear. In most cases they appear to promote host resistance by
      mobilizing leukocytes and activating immune functions that kill, expel, or
      sequester pathogens. In other cases, the chemokine system has been pirated by
      pathogens, especially protozoa and viruses, which have exploited host chemokine
      receptors as modes of cellular invasion or developed chemokine mimics and binding
      proteins that act as antagonists or inappropriate agonists. Understanding
      microbial mechanisms of chemokine evasion will potentially lead to novel
      antimicrobial and anti-inflammatory therapeutic agents.

PMID- 11585785
TI  - Antiviral actions of interferons.
AB  - Tremendous progress has been made in understanding the molecular basis of the
      antiviral actions of interferons (IFNs), as well as strategies evolved by viruses
      to antagonize the actions of IFNs. Furthermore, advances made while elucidating
      the IFN system have contributed significantly to our understanding in multiple
      areas of virology and molecular cell biology, ranging from pathways of signal
      transduction to the biochemical mechanisms of transcriptional and translational
      control to the molecular basis of viral pathogenesis. IFNs are approved
      therapeutics and have moved from the basic research laboratory to the clinic.
      Among the IFN-induced proteins important in the antiviral actions of IFNs are the
      RNA-dependent protein kinase (PKR), the 2',5'-oligoadenylate synthetase (OAS) and
      RNase L, and the Mx protein GTPases. Double-stranded RNA plays a central role in
      modulating protein phosphorylation and RNA degradation catalyzed by the IFN
      inducible PKR kinase and the 2'-5'-oligoadenylate-dependent RNase L,
      respectively, and also in RNA editing by the IFN-inducible RNA-specific adenosine
      deaminase (ADAR1). IFN also induces a form of inducible nitric oxide synthase
      (iNOS2) and the major histocompatibility complex class I and II proteins, all of
      which play important roles in immune response to infections. Several additional
      genes whose expression profiles are altered in response to IFN treatment and
      virus infection have been identified by microarray analyses. The availability of
      cDNA and genomic clones for many of the components of the IFN system, including
      IFN-alpha, IFN-beta, and IFN-gamma, their receptors, Jak and Stat and IRF signal
      transduction components, and proteins such as PKR, 2',5'-OAS, Mx, and ADAR, whose
      expression is regulated by IFNs, has permitted the generation of mutant proteins,
      cells that overexpress different forms of the proteins, and animals in which
      their expression has been disrupted by targeted gene disruption. The use of these
      IFN system reagents, both in cell culture and in whole animals, continues to
      provide important contributions to our understanding of the virus-host
      interaction and cellular antiviral response.

PMID- 11585789
TI  - Active immunization in the United States: developments over the past decade.
AB  - The Centers for Disease Control and Prevention has identified immunization as the
      most important public health advance of the 20th century. The purpose of this
      article is to review the changes that have taken place in active immunization in
      the United States over the past decade. Since 1990, new vaccines have become
      available to prevent five infectious diseases: varicella, rotavirus, hepatitis A,
      Lyme disease, and Japanese encephalitis virus infection. Improved vaccines have
      been developed to prevent Haemophilus influenzae type b, pneumococcus, pertussis,
      rabies, and typhoid infections. Immunization strategies for the prevention of
      hepatitis B, measles, meningococcal infections, and poliomyelitis have changed as
      a result of the changing epidemiology of these diseases. Combination vaccines are
      being developed to facilitate the delivery of multiple antigens, and improved
      vaccines are under development for cholera, influenza, and meningococcal disease.
      Major advances in molecular biology have enabled scientists to devise new
      approaches to the development of vaccines against diseases ranging from
      respiratory viral to enteric bacterial infections that continue to plague the
      world's population.

PMID- 11585788
TI  - Molecular detection of antimicrobial resistance.
AB  - The determination of antimicrobial susceptibility of a clinical isolate,
      especially with increasing resistance, is often crucial for the optimal
      antimicrobial therapy of infected patients. Nucleic acid-based assays for the
      detection of resistance may offer advantages over phenotypic assays. Examples are
      the detection of the methicillin resistance-encoding mecA gene in staphylococci,
      rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance
      determinants across the globe. However, molecular assays for the detection of
      resistance have a number of limitations. New resistance mechanisms may be missed,
      and in some cases the number of different genes makes generating an assay too
      costly to compete with phenotypic assays. In addition, proper quality control for
      molecular assays poses a problem for many laboratories, and this results in
      questionable results at best. The development of new molecular techniques, e.g.,
      PCR using molecular beacons and DNA chips, expands the possibilities for
      monitoring resistance. Although molecular techniques for the detection of
      antimicrobial resistance clearly are winning a place in routine diagnostics,
      phenotypic assays are still the method of choice for most resistance
      determinations. In this review, we describe the applications of molecular
      techniques for the detection of antimicrobial resistance and the current state of
      the art.

PMID- 11585792
TI  - A role for frizzled 3 in neural crest development.
AB  - Wnts are a large family of secreted molecules implicated in numerous
      developmental processes. Frizzled proteins are likely receptors for Wnts and are
      required for Wnt signaling in invertebrates. A large number of vertebrate
      frizzled genes have also been identified, but their roles in mediating specific
      responses to endogenous Wnts have not been well defined. Using a functional assay
      in Xenopus, we have performed a large screen to identify potential interactions
      between Wnts and frizzleds. We find that signaling by Xwnt1, but not other Wnts,
      can be specifically enhanced by frizzled 3 (Xfz3). As both Xfz3 and Xwnt1 are
      highly localized to dorsal neural tissues that give rise to neural crest, we
      examined whether Xfz3 mediates Xwnt1 signaling in the formation of neural crest.
      Xfz3 specifically induces neural crest in ectodermal explants and in embryos,
      similar to Xwnt1, and at lower levels of expression, synergizes with Xwnt1 in
      neural crest induction. Furthermore, loss of Xfz3 function, either by depletion
      with a Xfz3-directed morpholino antisense oligonucleotide or by expression of an
      inhibitory form of Xfz3 (Nfz3), prevents Xwnt1-dependent neural crest induction
      in ectodermal explants and blocks neural crest formation in whole embryos. These
      results show that Xfz3 is required for Xwnt1 signaling in the formation of the
      neural crest in the developing vertebrate embryo.

PMID- 11585790
TI  - Ross River virus transmission, infection, and disease: a cross-disciplinary
      review.
AB  - Ross River virus (RRV) is a fascinating, important arbovirus that is endemic and
      enzootic in Australia and Papua New Guinea and was epidemic in the South Pacific
      in 1979 and 1980. Infection with RRV may cause disease in humans, typically
      presenting as peripheral polyarthralgia or arthritis, sometimes with fever and
      rash. RRV disease notifications in Australia average 5,000 per year. The first
      well-described outbreak occurred in 1928. During World War II there were more
      outbreaks, and the name epidemic polyarthritis was applied. During a 1956
      outbreak, epidemic polyarthritis was linked serologically to a group A arbovirus
      (Alphavirus). The virus was subsequently isolated from Aedes vigilax mosquitoes
      in 1963 and then from epidemic polyarthritis patients. We review the literature
      on the evolutionary biology of RRV, immune response to infection, pathogenesis,
      serologic diagnosis, disease manifestations, the extraordinary variety of
      vertebrate hosts, mosquito vectors, and transmission cycles, antibody prevalence,
      epidemiology of asymptomatic and symptomatic human infection, infection risks,
      and public health impact. RRV arthritis is due to joint infection, and treatment
      is currently based on empirical anti-inflammatory regimens. Further research on
      pathogenesis may improve understanding of the natural history of this disease and
      lead to new treatment strategies. The burden of morbidity is considerable, and
      the virus could spread to other countries. To justify and design preventive
      programs, we need accurate data on economic costs and better understanding of
      transmission and behavioral and environmental risks.

PMID- 11585793
TI  - Kermit, a frizzled interacting protein, regulates frizzled 3 signaling in neural
      crest development.
AB  - Wnts are a family of secreted glycoproteins that are important for multiple steps
      in early development. Accumulating evidence suggests that frizzled genes encode
      receptors for Wnts. However, the mechanism through which frizzleds transduce a
      signal and the immediate downstream components that convey that signal are
      unclear. We have identified a new protein, Kermit, that interacts specifically
      with the C-terminus of Xenopus frizzled-3 (Xfz3). Kermit is a 331 amino acid
      protein with a central PDZ domain. Kermit mRNA is expressed throughout Xenopus
      development and is localized to neural tissue in a pattern that overlaps Xfz3
      expression temporally and spatially. Co-expression of Xfz3 and Kermit results in
      a dramatic translocation of Kermit to the plasma membrane. Inhibition of Kermit
      function with morpholino antisense oligonucleotides directed against the 5'
      untranslated region of Kermit mRNA blocks neural crest induction by Xfz3, and
      this is rescued by co-injection of mRNA encoding the Kermit open reading frame.
      These observations suggest that Kermit is required for Wnt/frizzled signaling in
      neural crest development. To the best of our knowledge, Kermit is the first
      protein identified that interacts directly with the cytoplasmic portion of
      frizzleds to modulate their signaling activity.

PMID- 11585791
TI  - Extended-spectrum beta-lactamases in the 21st century: characterization,
      epidemiology, and detection of this important resistance threat.
AB  - Beta-lactamases continue to be the leading cause of resistance to beta-lactam
      antibiotics among gram-negative bacteria. In recent years there has been an
      increased incidence and prevalence of extended-spectrum beta-lactamases (ESBLs),
      enzymes that hydrolyze and cause resistance to oxyimino-cephalosporins and
      aztreonam. The majority of ESBLs are derived from the widespread broad-spectrum
      beta-lactamases TEM-1 and SHV-1. There are also new families of ESBLs, including
      the CTX-M and OXA-type enzymes as well as novel, unrelated beta-lactamases.
      Several different methods for the detection of ESBLs in clinical isolates have
      been suggested. While each of the tests has merit, none of the tests is able to
      detect all of the ESBLs encountered. ESBLs have become widespread throughout the
      world and are now found in a significant percentage of Escherichia coli and
      Klebsiella pneumoniae strains in certain countries. They have also been found in
      other Enterobacteriaceae strains and Pseudomonas aeruginosa. Strains expressing
      these beta-lactamases will present a host of therapeutic challenges as we head
      into the 21st century.

PMID- 11585794
TI  - Notch signaling is required for arterial-venous differentiation during embryonic
      vascular development.
AB  - Recent evidence indicates that acquisition of artery or vein identity during
      vascular development is governed, in part, by genetic mechanisms. The artery
      specific expression of a number of Notch signaling genes in mouse and zebrafish
      suggests that this pathway may play a role in arterial-venous cell fate
      determination during vascular development. We show that loss of Notch signaling
      in zebrafish embryos leads to molecular defects in arterial-venous
      differentiation, including loss of artery-specific markers and ectopic expression
      of venous markers within the dorsal aorta. Conversely, we find that ectopic
      activation of Notch signaling leads to repression of venous cell fate. Finally,
      embryos lacking Notch function exhibit defects in blood vessel formation similar
      to those associated with improper arterial-venous specification. Our results
      suggest that Notch signaling is required for the proper development of arterial
      and venous blood vessels, and that a major role of Notch signaling in blood
      vessels is to repress venous differentiation within developing arteries. Movies
      available on-line

PMID- 11585797
TI  - Initiation of facial motoneurone migration is dependent on rhombomeres 5 and 6.
AB  - In mammals, facial branchiomotor (FBM) neurones are born in ventral rhombomere
      (r) 4 and migrate through r5 to dorsal r6 where they form the facial motor
      nucleus. This pattern of migration gives rise to the distinctive appearance of
      the internal genu of the facial nerve, which is lacking in birds. To distinguish
      between extrinsic cues and intrinsic factors in the caudal migration of FBM
      neurones, this study takes advantage of the evolutionary migratory difference
      between mouse and chick in generating mouse-chick chimaeras in ovo. After the
      homotopic transplantation of mouse r5 and/or r6 into a chick embryo, chick
      ventral r4 neurones redirected their cell bodies towards the ectopic mouse source
      and followed a caudal migratory path, reminiscent of mouse FBM neurones. In a
      second series of grafting experiments, when mouse r4 was transplanted in place of
      chick r4, mouse r4 neurones were unable to migrate into chick r5, although mouse
      and chick cells were able to mix freely within r4. Thus, these data suggest that
      local environmental cues embedded in mouse r5 and r6 are directly involved in
      initiating caudal migration of FBM neurones. In addition, they demonstrate that
      chick FBM neurones are competent to recapitulate a migratory behaviour that has
      been lost during avian phylogeny.

PMID- 11585798
TI  - Regulation of the muscle-specific expression and function of an ascidian T-box
      gene, As-T2.
AB  - The Tbx6 T-box genes are expressed in somite precursor cells of vertebrate
      embryos and are essential for the differentiation of paraxial mesoderm. However,
      it is unclear how spatial regulation of the gene expression is controlled and how
      the genes function to promote muscle differentiation. The Tbx6-related gene As-T2
      of the ascidian Halocynthia roretzi is first expressed very transiently in
      endodermal cells around the 32- approximately 44-cell stage, is then expressed
      distinctly and continuously in muscle precursor cells, and later in epidermal
      cells situated in the distal tip region of the elongating tail. We now show that
      inhibition of As-T2-mediated transcriptional activation by microinjection of As
      T2/En(R) into one-cell embryos resulted in suppression of the expression of the
      muscle-specific actin gene (HrMA4) and myosin heavy chain gene (HrMHC), but the
      injection did not affect the differentiation of endodermal cells or tail tip
      cells, suggesting that the primary function of As-T2 is associated with muscle
      cell differentiation. The 5' flanking region of As-T2 contains two promoter
      modules that regulate its specific expression: a distal module that responsible
      for its specific expression in the tail, and a proximal module required for its
      muscle-specific expression. Around the proximal module, there are two putative T
      protein-binding motifs (TTCACACTT). Co-injection of an As-T2/lacZ construct with
      or without the T-binding motifs together with As-T2 mRNA revealed that these
      motifs are essential for autoregulatory activation of the gene itself. In
      addition, we found that the minimal promoter regions of HrMA4 and HrMHC contain T
      binding motifs. Co-injection of HrMA4/lacZ or HrMHC/lacZ containing the T-binding
      motifs along with As-T2 mRNA revealed that As-T2 protein binds to these motifs to
      upregulate the gene activity. Taking into account the recent finding of maternal
      molecules for muscle differentiation, we propose a model for a genetic cascade
      that includes As-T2 as a regulator of muscle cell differentiation in the ascidian
      embryo.

PMID- 11585795
TI  - Multiple effects of artemin on sympathetic neurone generation, survival and
      growth.
AB  - To define the role of artemin in sympathetic neurone development, we have studied
      the effect of artemin on the generation, survival and growth of sympathetic
      neurones in low-density dissociated cultures of mouse cervical and thoracic
      paravertebral sympathetic ganglia at stages throughout embryonic and postnatal
      development. Artemin promoted the proliferation of sympathetic neuroblasts and
      increased the generation of new neurones in cultures established from E12 to E14
      ganglia. Artemin also exerted a transient survival-promoting action on newly
      generated neurones during these early stages of development. Between E16 and P8,
      artemin exerted no effect on survival, but by P12, as sympathetic neurones begin
      to acquire neurotrophic factor independent survival, artemin once again enhanced
      survival, and by P20 it promoted survival as effectively as nerve growth factor
      (NGF). During this late period of development, artemin also enhanced the growth
      of neurites from cultured neurones more effectively than NGF. Confirming the
      physiological relevance of the mitogenic action of artemin on cultured
      neuroblasts, there was a marked reduction in the rate of neuroblast proliferation
      in the sympathetic ganglia of mice lacking the GFRalpha3 subunit of the artemin
      receptor. These results indicate that artemin exerts several distinct effects on
      the generation, survival and growth of sympathetic neurones at different stages
      of development.

PMID- 11585796
TI  - Embryonic control of epidermal cell patterning in the root and hypocotyl of
      Arabidopsis.
AB  - A position-dependent pattern of epidermal cell types is produced during the
      development of the Arabidopsis seedling root and hypocotyl. To understand the
      origin and regulation of this patterning mechanism, we have examined the
      embryonic expression of the GLABRA2 (GL2) gene, which encodes a cell-type
      specific transcription factor. Using in situ RNA hybridization and a sensitive
      GL2::GFP reporter, we discovered that a position-dependent pattern of GL2
      expression is established within protodermal cells at the heart stage and is
      maintained throughout the remainder of embryogenesis. In addition, we show that
      an exceptional GL2 expression character and epidermal cell pattern arises during
      development of the root-hypocotyl junction, which represents an anatomical
      transition zone. Furthermore, we find that two of the genes regulating seedling
      epidermal patterning, TRANSPARENT TESTA GLABRA (TTG) and WEREWOLF (WER), also
      control the embryonic GL2 pattern, whereas the CAPRICE (CPC) and GL2 genes are
      not required to establish this pattern. These results indicate that position
      dependent patterning of epidermal cell types begins at an early stage of
      embryogenesis, before formation of the apical meristems and shortly after the
      cellular anatomy of the protoderm and outer ground tissue layer is established.
      Thus, epidermal cell specification in the Arabidopsis seedling relies on the
      embryonic establishment of a patterning mechanism that is perpetuated
      postembryonically.

PMID- 11585799
TI  - Downregulation of the tissue-specific transcription factor Fork head by Broad
      Complex mediates a stage-specific hormone response.
AB  - Drosophila development is coordinated by pulses of the steroid hormone 20
      hydroxyecdysone (20E). During metamorphosis, the 20E-inducible Broad-Complex (BR
      C) gene plays a key role in the genetic hierarchies that transduce the hormone
      signal, being required for the destruction of larval tissues and numerous aspects
      of adult development. Most of the known BR-C target genes, including the salivary
      gland secretion protein (Sgs) genes, are terminal differentiation genes that are
      thought to be directly regulated by BR-C-encoded transcription factors. Here, we
      show that repression of Sgs expression is indirectly controlled by the BR-C
      through transcriptional down-regulation of fork head, a tissue-specific gene that
      plays a central role in salivary gland development and is required for Sgs
      expression. Our results demonstrate that integration of a tissue-specific
      regulatory gene into a 20E-controlled genetic hierarchy provides a mechanism for
      hormonal repression. Furthermore, they suggest that the BR-C is placed at a
      different position within the 20E-controlled hierarchies than previously assumed,
      and that at least part of its pleiotropic functions are mediated by tissue
      specific regulators.

PMID- 11585800
TI  - Blastomeres arising from the first cleavage division have distinguishable fates
      in normal mouse development.
AB  - Two independent studies have recently suggested similar models in which the
      embryonic and abembryonic parts of the mouse blastocyst become separated already
      by the first cleavage division. However, no lineage tracing studies carried out
      so far on early embryos provide the support for such a hypothesis. Thus, to re
      examine the fate of blastomeres of the two-cell mouse embryo, we have undertaken
      lineage tracing studies using a non-perturbing method. We show that two-cell
      stage blastomeres have a strong tendency to develop into cells that comprise
      either the embryonic or the abembryonic parts of the blastocyst. Moreover, the
      two-cell stage blastomere that is first to divide will preferentially contribute
      its progeny to the embryonic part. Nevertheless, we find that the blastocyst
      embryonic-abembryonic axis is not perfectly orthogonal to the first cleavage
      plane, but often shows some angular displacement from it. Consequently, there is
      a boundary zone adjacent to the interior margin of the blastocoel that is
      populated by cells derived from both earlier and later dividing blastomeres. The
      majority of cells that inhabit this boundary region are, however, derived from
      the later dividing two-cell stage blastomere that contributes predominantly to
      the abembryonic part of the blastocyst. Thus, at the two-cell stage it is already
      possible to predict which cell will contribute a greater proportion of its
      progeny to the abembryonic part of the blastocyst (region including the
      blastocyst cavity) and which to the embryonic part (region containing the inner
      cell mass) that will give rise to the embryo proper.

PMID- 11585801
TI  - Determinants of T box protein specificity.
AB  - Members of the T box family of transcription factors play important roles in
      early development. Different members of the family exert different effects and
      here we show that much of the specificity of the Xenopus T box proteins Xbra,
      VegT and Eomesodermin resides in the DNA-binding domain, or T box. Binding site
      selection experiments show that the three proteins bind the same core sequence,
      but they select paired sites that differ in their orientation and spacing. Lysine
      149 of Xbra is conserved in all Brachyury homologues, while the corresponding
      amino acid in VegT and Eomesodermin is asparagine. Mutation of this amino acid to
      lysine changes the inductive abilities of VegT and Eomesodermin to resemble that
      of Xbra.

PMID- 11585802
TI  - In utero fate mapping reveals distinct migratory pathways and fates of neurons
      born in the mammalian basal forebrain.
AB  - Recent studies suggest that neurons born in the developing basal forebrain
      migrate long distances perpendicularly to radial glia and that many of these
      cells reach the developing neocortex. This form of tangential migration, however,
      has not been demonstrated in vivo, and the sites of origin, pathways of migration
      and final destinations of these neurons in the postnatal brain are not fully
      understood. Using ultrasound-guided transplantation in utero, we have mapped the
      migratory pathways and fates of cells born in the lateral and medial ganglionic
      eminences (LGE and MGE) in 13.5-day-old mouse embryos. We demonstrate that LGE
      and MGE cells migrate along different routes to populate distinct regions in the
      developing brain. We show that LGE cells migrate ventrally and anteriorly, and
      give rise to the projecting medium spiny neurons in the striatum, nucleus
      accumbens and olfactory tubercle, and to granule and periglomerular cells in the
      olfactory bulb. By contrast, we show that the MGE is a major source of neurons
      migrating dorsally and invading the developing neocortex. MGE cells migrate into
      the neocortex via the neocortical subventricular zone and differentiate into the
      transient subpial granule neurons in the marginal zone and into a stable
      population of GABA-, parvalbumin- or somatostatin-expressing interneurons
      throughout the cortical plate.

PMID- 11585803
TI  - GDNF and neurturin are target-derived factors essential for cranial
      parasympathetic neuron development.
AB  - During development, parasympathetic ciliary ganglion neurons arise from the
      neural crest and establish synaptic contacts on smooth and striate muscle in the
      eye. The factors that promote the ciliary ganglion pioneer axons to grow toward
      their targets have yet to be determined. Here, we show that glial cell line
      derived neurotrophic factor (GDNF) and neurturin (NRTN) constitute target-derived
      factors for developing ciliary ganglion neurons. Both GDNF and NRTN are secreted
      from eye muscle located in the target and trajectory pathway of ciliary ganglion
      pioneer axons during the period of target innervation. After this period,
      however, the synthesis of GDNF declines markedly, while that of NRTN is
      maintained throughout the cell death period. Furthermore, both in vitro and in
      vivo function-blocking of GDNF at early embryonic ages almost entirely suppresses
      ciliary axon outgrowth. These results demonstrate that target-derived GDNF is
      necessary for ciliary ganglion neurons to innervate ciliary muscle in the eye.
      Since the down-regulation of GDNF in the eye is accompanied by down-regulation of
      GFRalpha1 and Ret, but not of GFRalpha2, in innervating ciliary ganglion neurons,
      the results also suggest that target-derived GDNF regulates the expression of its
      high-affinity coreceptors.

PMID- 11585804
TI  - Role of Goosecoid, Xnot and Wnt antagonists in the maintenance of the notochord
      genetic programme in Xenopus gastrulae.
AB  - The Xenopus trunk organiser recruits neighbouring tissues into secondary trunk
      axial and paraxial structures and itself differentiates into notochord. The
      inductive properties of the trunk organiser are thought to be mediated by the
      secretion of bone morphogenetic protein (BMP) antagonists. Ectopic repression of
      BMP signals on the ventral side is sufficient to mimic the inductive properties
      of the trunk organiser. Resultant secondary trunks contain somite and neural
      tube, but no notochord. We show that inhibition of BMP signalling is sufficient
      for the initiation of the trunk organiser genetic programme at the onset of
      gastrulation. During late gastrulation, however, this programme is lost, due to
      an invasion of secreted Wnts from neighbouring tissues. Maintenance of this
      programme requires co-repression of BMP and Wnt signalling within the presumptive
      notochord region. To shed light on the molecular cascade that leads to the
      repression of the Wnt pathway, we looked for individual organiser genes whose
      overexpression could complement the inhibition of BMP signalling to promote
      notochord formation in the secondary trunks. Two genes, gsc and Xnot, were thus
      identified and shown to act in different ways. Xnot acts as a transcriptional
      repressor within the mesodermal region. Gsc acts in deeper vegetal cells, where
      it regulates Frzb expression to maintain Xnot expression in the neighbouring
      notochord territory. These results suggest that, during gastrulation, the
      necessary repression of Wnt/beta-catenin signalling in notochord precursors is
      achieved by the action of secreted inhibitors, such as Frzb, emitted by gsc
      expressing dorsal vegetal cells.

PMID- 11585805
TI  - New B-type cyclin synthesis is required between meiosis I and II during Xenopus
      oocyte maturation.
AB  - Progression through meiosis requires two waves of maturation promoting factor
      (MPF) activity corresponding to meiosis I and meiosis II. Frog oocytes contain a
      pool of inactive "pre-MPF" consisting of cyclin-dependent kinase 1 bound to B
      type cyclins, of which we now find three previously unsuspected members, cyclins
      B3, B4 and B5. Protein synthesis is required to activate pre-MPF, and we show
      here that this does not require new B-type cyclin synthesis, probably because of
      a large maternal stockpile of cyclins B2 and B5. This stockpile is degraded after
      meiosis I and consequently, the activation of MPF for meiosis II requires new
      cyclin synthesis, principally of cyclins B1 and B4, whose translation is strongly
      activated after meiosis I. If this wave of new cyclin synthesis is ablated by
      antisense oligonucleotides, the oocytes degenerate and fail to form a second
      meiotic spindle. The effects on meiotic progression are even more severe when all
      new protein synthesis is blocked by cycloheximide added after meiosis I, but can
      be rescued by injection of indestructible B-type cyclins. B-type cyclins and MPF
      activity are required to maintain c-mos and MAP kinase activity during meiosis
      II, and to establish the metaphase arrest at the end of meiotic maturation. We
      discuss the interdependence of c-mos and MPF, and reveal an important role for
      translational control of cyclin synthesis between the two meiotic divisions.

PMID- 11585806
TI  - Facultative heterochromatization in parahaploid male mealybugs: involvement of a
      heterochromatin-associated protein.
AB  - The behavior of chromosomes during development of the mealybug Planococcus citri
      provides one of the most dramatic examples of facultative heterochromatization.
      In male embryos, the entire haploid paternal chromosome set becomes
      heterochromatic at mid-cleavage. Male mealybugs are thus functionally haploid,
      owing to heterochromatization (parahaploidy). To understand the mechanisms
      underlying facultative heterochromatization in male mealybugs, we have
      investigated the possible involvement of an HP-1-like protein in this process. HP
      1 is a conserved, nonhistone chromosomal protein with a proposed role in
      heterochromatinization in other species. It was first identified in Drosophila
      melanogaster as a protein enriched in the constitutive heterochromatin of
      polytene chromosome. Using a monoclonal antibody raised against the Drosophila HP
      1 in immunoblot and immunocytological experiments, we provide evidence for the
      presence of an HP-1-like in Planococcus citri males and females. In males, the HP
      1-like protein is preferentially associated with the male-specific
      heterochromatin. In the developing male embryos, its appearance precedes the
      onset of heterochromatization. In females, the HP-1-like protein displays a
      scattered but reproducible localization pattern along chromosomes. The results
      indicate a role for an HP-1-like protein in the facultative heterochromatization
      process.

PMID- 11585807
TI  - Cell survival and proliferation are modified by insulin-like growth factor 2
      between days 9 and 10 of mouse gestation.
AB  - The size of mammalian species involves the interaction of multiple genetic
      modifiers that control the timing and extent of growth mechanisms. Disruption of
      the paternal allele of the imprinted embryonic gene coding for insulin-like
      growth factor 2 (IGF2, Igf2(+m/-p)), results in viable mice that are 60% the
      weight of wild-type littermates. Differences in weight are first detected at
      embryonic day (E) 11, and the growth deficit is maintained throughout life. We
      report the mechanisms that account for this unusual phenotype. In order to
      quantify growth, we used novel methods to generate single cell suspensions of
      post-implantation mouse embryos. We were then able to quantify cell number, cell
      proliferation and cell death between E8.5 and E11.5 using flow cytometry.
      Determination of total embryo cell number also allowed us to time litters by a
      method other than by plugging. Wild-type and Igf2(+m/-p) embryos accumulated
      similar total cell numbers up to E9.25, but cell number began to diverge by
      around E9.5, with significant differences by E11 (75% of wild type). A relative
      increase in pyknotic nuclei, sub-GI cytometry counts and caspase activity, all
      indicative of cell death, occurred in Igf2(+m/-p) embryos at E9.25, reverting to
      wild-type levels by E9.75. This was followed at E9.75 by a significant reduction
      in the proportion of cells in S phase, quantified by S-phase cytometry counts and
      BrdU labelling. No significant differences in cell size were detected. We
      conclude that the majority of the cell number differences between wild-type and
      Igf2(+m/-p) mice can be accounted for by modification of cell survival and
      proliferation during the period (E9 to E10) of post-implantation development.

PMID- 11585808
TI  - A positive role for Short gastrulation in modulating BMP signaling during
      dorsoventral patterning in the Drosophila embryo.
AB  - Positional information in the dorsoventral axis of the Drosophila embryo is
      encoded by a BMP activity gradient formed by synergistic signaling between the
      BMP family members Decapentaplegic (DPP) and Screw (SCW). short gastrulation
      (sog), which is functionally homologous to Xenopus Chordin, is expressed in the
      ventrolateral regions of the embryo and has been shown to act as a local
      antagonist of BMP signaling. Here we demonstrate that SOG has a second function,
      which is to promote BMP signaling on the dorsal side of the embryo. We show that
      a weak, homozygous-viable sog mutant is enhanced to lethality by reduction in the
      activities of the Smad family members Mad or Medea, and that the lethality is
      caused by defects in the molecular specification and subsequent cellular
      differentiation of the dorsal-most cell type, the amnioserosa. While previous
      data had suggested that the negative function of SOG is directed against SCW, we
      present data that suggests that the positive activity of SOG is directed towards
      DPP. We demonstrate that Chordin shares the same apparent ligand specificity as
      does SOG, preferentially inhibiting SCW but not DPP activity. However, in
      Drosophila assays Chordin does not have the same capacity to elevate BMP
      signaling as does SOG, identifying a functional difference in the otherwise well
      conserved process of dorsoventral pattern formation in arthropods and chordates.

PMID- 11585809
TI  - Requirement of NF-kappaB/Rel for the development of hair follicles and other
      epidermal appendices.
AB  - NF-kappaB/Rel transcription factors and IkappaB kinases (IKK) are essential for
      inflammation and immune responses, but also for bone-morphogenesis, skin
      proliferation and differentiation. Determining their other functions has
      previously been impossible, owing to embryonic lethality of NF-kappaB/Rel or IKK
      deficient animals. Using a gene targeting approach we have ubiquitously expressed
      an NF-kappaB super-repressor to investigate NF-kappaB functions in the adult.
      Mice with suppressed NF-kappaB revealed defective early morphogenesis of hair
      follicles, exocrine glands and teeth, identical to Eda (tabby) and Edar
      (downless) mutant mice. These affected epithelial appendices normally display
      high NF-kappaB activity, suppression of which resulted in increased apoptosis,
      indicating that NF-kappaB acts as a survival factor downstream of the tumor
      necrosis factor receptor family member EDAR. Furthermore, NF-kappaB is required
      for peripheral lymph node formation and macrophage function.

PMID- 11585810
TI  - Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons
      and ligaments.
AB  - Little is known about the genesis and patterning of tendons and other connective
      tissues, mostly owing to the absence of early markers. We have found that
      Scleraxis, a bHLH transcription factor, is a highly specific marker for all the
      connective tissues that mediate attachment of muscle to bone in chick and mouse,
      including the limb tendons, and show that early scleraxis expression marks the
      progenitor cell populations for these tissues. In the early limb bud, the tendon
      progenitor population is found in the superficial proximomedial mesenchyme. Using
      the scleraxis gene as a marker we show that these progenitors are induced by
      ectodermal signals and restricted by bone morphogenetic protein (BMP) signaling
      within the mesenchyme. Application of Noggin protein antagonizes this endogenous
      BMP activity and induces ectopic scleraxis expression. However, the presence of
      excess tendon progenitors does not lead to the production of additional or longer
      tendons, indicating that additional signals are required for the final formation
      of a tendon. Finally, we show that the endogenous expression of noggin within the
      condensing digit cartilage contributes to the induction of distal tendons.

PMID- 11585811
TI  - Differential regulation of endochondral bone growth and joint development by
      FGFR1 and FGFR3 tyrosine kinase domains.
AB  - Fibroblast growth factor receptors (FGFR) 1 and 3 have distinct mitogenic
      activities in vitro. In several cultured cell lines, FGFR1 transmits a potent
      mitogenic signal, whereas FGFR3 has little or no mitogenic activity. However, in
      other in vitro assays the FGFR3 intracellular domain is comparable with that of
      FGFR1. In vivo, FGFR3 negatively regulates chondrocyte proliferation and
      differentiation, and activating mutations are the molecular etiology of
      achondroplasia. By contrast, FGFR1 transmits a proliferative signal in various
      cell types in vivo. These observations suggest that inhibition of the
      proliferating chondrocyte could be a unique property of FGFR3 or, alternatively,
      a unique property of the proliferating chondrocyte. To test this hypothesis,
      FGFR1 signaling was activated in the growth plate in cells that normally express
      FGFR3. Comparison of transgenic mice with an activated FGFR1 signaling pathway
      with an achondroplasia-like mouse that expresses a similarly activated FGFR3
      signaling pathway demonstrated that both transgenes result in a similar
      achondroplasia-like dwarfism. These data demonstrate that suppression of
      mitogenic activity by FGFR signaling is a property that is unique to growth plate
      chondrocytes. Surprisingly, we observed that in transgenic mice expressing an
      activated FGFR, some synovial joints failed to develop and were replaced by
      cartilage. The defects in the digit joints phenocopied the symphalangism that
      occurs in Apert syndrome and the number of affected joints was dependent on
      transgene dose. In contrast to the phenotype in the growth plate, the joint
      phenotype was more severe in transgenic mice with an activated FGFR1 signaling
      pathway. The failure of joint development resulted from expanded chondrification
      in the presumptive joint space, suggesting a crucial role for FGF signaling in
      regulating the transition of condensed mesenchyme to cartilage and in defining
      the boundary of skeletal elements.

PMID- 11585812
TI  - A glucocorticoid/retinoic acid receptor chimera that displays cytoplasmic/nuclear
      translocation in response to retinoic acid. A real time sensing assay for nuclear
      receptor ligands.
AB  - Members of the nuclear receptor superfamily play key roles in a host of
      physiologic and pathologic processes from embryogenesis to cancer. Some members,
      including the retinoic acid receptor (RAR), are activated by ligand binding but
      are unaffected in their subcellular distribution, which is predominantly nuclear.
      In contrast, several members of the steroid receptor family, including the
      glucocorticoid receptor, are cytoplasmic and only translocate to the nucleus
      after ligand binding. We have constructed chimeras between RAR and glucocorticoid
      receptor that selectively respond to RAR agonists but display cytoplasmic
      localization in the absence of ligand. These chimeric receptors manifest both
      nuclear translocation and gene activation functions in response to physiological
      concentrations of RAR ligands. The ability to achieve regulated subcellular
      trafficking with a heterologous ligand binding domain has implications both for
      current models of receptor translocation and for structural-functional
      conservation of ligand binding domains broadly across the receptor superfamily.
      When coupled to the green fluorescent protein, chimeric receptors offer a
      powerful new tool to 1) study mechanisms of steroid receptor translocation, 2)
      detect dynamic and graded distributions of ligands in complex microenvironments
      such as embryos, and 3) screen for novel ligands of "orphan" receptors in vivo.

PMID- 11585813
TI  - Monocyte differentiation to macrophage requires interferon regulatory factor 7.
AB  - Interferon regulatory factors are a growing family of transcription factor that
      have been implicated in cellular events such as cell-growth regulation, antiviral
      defense, and development of the immune system. Interferon regulatory factor 7
      (IRF-7) is expressed predominantly in lymphoid tissues and has been studied
      extensively in the context of viral infection and the induction of interferon and
      cytokine gene expression. In this paper, the involvement of IRF-7 in monocyte
      differentiation was examined in U937, HL60, and human primary macrophages. We
      report the induction of IRF-7 expression by 12-O-tetradecanoylphorbol-13-acetate
      in U937 and HL60 cells and demonstrate that this induction is essential for the
      monocyte differentiation to macrophages. We show that the monocyte
      differentiation is inhibited in cells expressing a dominant negative IRF-7
      mutant, as evidenced by decreased expression of two macrophage-differentiation
      markers, CD11b and CD11c, and impaired phagocytic activity. In addition, we
      demonstrate that overexpression of IRF-7 is sufficient to trigger monocyte
      differentiation and to induce cell cycle arrest. The identification of IRF-7 as a
      key regulator in monocyte differentiation suggests a novel function of IRF-7 in
      innate immunity.

PMID- 11585814
TI  - Effects of acetylation of histone H4 at lysines 8 and 16 on activity of the Hat1
      histone acetyltransferase.
AB  - During nucleosome assembly in vivo, newly synthesized histone H4 is specifically
      diacetylated on lysines 5 and 12 within the H4 NH(2)-terminal tail domain. The
      highly conserved "K5/K12" deposition pattern of acetylation is thought to be
      generated by the Hat1 histone acetyltransferase, which in vivo is found in the
      HAT-B complex. In the following report, the activity and substrate specificity of
      the human HAT-B complex and of recombinant yeast Hat1p have been examined, using
      synthetic H4 NH(2)-terminal peptides as substrates. As expected, the unacetylated
      H4 peptide was a good substrate for acetylation by yeast Hat1p and human HAT-B,
      while the K5/K12-diacetylated peptide was not significantly acetylated. Notably,
      an H4 peptide previously diacetylated on lysines 8 and 16 was a very poor
      substrate for acetylation by either yeast Hat1p or human HAT-B. Treating the
      K8/K16-diacetylated peptide with histone deacetylase prior to the HAT-B reaction
      raised acetylation at K5/K12 to 70-80% of control levels. These results present
      strong support for the model of H4-Hat1p interaction proposed by Dutnall et al.
      (Dutnall, R. N., Tafrov, S. T., Sternglanz, R., and Ramakrishnan, V. (1998) Cell
      94, 427-438) and provide evidence for the first time that site-specific
      acetylation of histones can regulate the acetylation of other substrate sites.

PMID- 11585815
TI  - Early steps of Bacillus subtilis primosome assembly.
AB  - Primosomes are nucleoprotein assemblies designed for the activation of DNA
      replication forks. Their primary role is to recruit the replicative helicase onto
      single-stranded DNA. The "replication restart" primosome, defined in Escherichia
      coli, is involved in the reactivation of arrested replication forks. Binding of
      the PriA protein to forked DNA triggers its assembly. PriA is conserved in
      bacteria, but its primosomal partners are not. In Bacillus subtilis, genetic
      analysis has revealed three primosomal proteins, DnaB, DnaD, and DnaI, that have
      no obvious homologues in E. coli. Interestingly, they are involved in primosome
      function both at arrested replication forks and at the chromosomal origin. Our
      biochemical analysis of the DnaB and DnaD proteins unravels their role in
      primosome assembly. They are both multimeric and bind individually to DNA.
      Furthermore, DnaD stimulates DnaB binding activities. DnaD alone and the
      DnaD/DnaB pair interact specifically with PriA of B. subtilis on several DNA
      substrates. This suggests that the nucleoprotein assembly is sequential in the
      PriA, DnaD, DnaB order. The preferred DNA substrate mimics an arrested DNA
      replication fork with unreplicated lagging strand, structurally identical to a
      product of recombinational repair of a stalled replication fork.

PMID- 11585816
TI  - p21-activated kinase-1 (PAK1) inhibition of the human scavenger receptor class B,
      type I promoter in macrophages is independent of PAK1 kinase activity, but
      requires the GTPase-binding domain.
AB  - Scavenger receptor class B, type I (SR-BI), is a high density lipoprotein
      receptor that mediates the flux of cholesterol between high density lipoprotein
      and cells. Recent evidence suggests that SR-BI plays a role in atherosclerosis
      and that inflammatory mediators down-regulate SR-BI in the macrophage. The
      purpose of this study was to evaluate the ability of lipopolysaccharide (LPS) to
      down-regulate the activity of the human SR-BI promoter in the macrophage and to
      delineate the mechanisms involved. Experiments with cultured cells and in vivo
      derived macrophages showed that LPS has a powerful suppressive effect on SR-BI
      expression both in vitro and in vivo. Transient transfection studies demonstrated
      that LPS represses SR-BI promoter activity in the macrophage cell line RAW 264.7.
      Cotransfection with either a constitutively active p21-activated protein kinase-1
      (PAK1) construct (T423E) or a kinase-deficient PAK1 construct (K299R) resulted in
      repression of the SR-BI promoter, similar to LPS. These results demonstrate that
      PAK1-mediated down-regulation of the SR-BI promoter is independent of PAK1 kinase
      activity and suggest that PAK1 mediates the LPS-induced decrease in promoter
      activity. Cotransfection with constitutively active Cdc42 or Rac expression
      constructs also resulted in down-regulation of the promoter; whereas the dominant
      negative Cdc42 and Rac constructs elevated basal promoter activity and blunted
      the LPS response. Cotransfection of PAK1 constructs containing mutations in both
      the kinase domain and the Cdc42/Rac-binding domain attenuated the PAK1-mediated
      down-regulation of the promoter, suggesting that Rac and Cdc42 are required for
      PAK1-mediated decreases in SR-BI promoter activity. 5'-Deletion analysis and gel
      shift data suggest that LPS inhibits binding of a novel transcription factor to a
      myeloid zing finger protein-1-like element (-476 to -456) in the human SR-BI
      promoter. These results demonstrate that the PAK1 pathway down-regulates the SR
      BI promoter and suggest that activation of this pathway may play an important
      role in cholesterol trafficking in the vessel wall.

PMID- 11585817
TI  - Low levels of IFN-gamma down-regulate the integrin-dependent adhesion of B cells
      by activating a pathway that interferes with cytoskeleton rearrangement.
AB  - In order to fully mature and participate in the humoral immune response, immature
      B cells must first migrate into specific areas in the spleen where they
      differentiate into mature cells. However, before their maturation in the spleen,
      immature B cells must be excluded from non-splenic secondary lymphoid organs
      where any antigen encounter would lead to the death of the cells because of the
      negative selection process. We have recently shown that immature B cells can
      actively exclude themselves from antigen-enriched sites by down-regulating their
      integrin-mediated adhesion in a process mediated by interferon-gamma (IFN-gamma).
      In this study, we followed the pathway by which IFN-gamma regulates the homing of
      B cells. We show here that the inhibitory signal of IFN-gamma is transmitted
      through the IFN-gamma receptor whose engagement leads to the activation of PI3K.
      This PI3K activation subsequently leads to the inhibition of PKCalpha
      phosphorylation and cytoskeleton rearrangement required for promoting integrin
      mediated adhesion and migration of B cells.

PMID- 11585818
TI  - A novel transrepression pathway of c-Myc. Recruitment of a transcriptional
      corepressor complex to c-Myc by MM-1, a c-Myc-binding protein.
AB  - The protooncogene product c-Myc plays a role in transcription regulation both for
      activation and repression. While transactivation pathways of c-Myc either from
      the N-proximal or the C-proximal region that is linked to the chromatin
      remodeling complex have been identified, a transrepression pathway had been
      identified only from the C-proximal region via Max and Mad that recruit the
      histone deacetylase (HDAC) complex. We have reported that a novel c-Myc-binding
      protein, MM-1, repressed the E-box-dependent transcription activity of c-Myc
      (Mori, K., Maeda, Y., Kitaura, H., Taira, T., Iguchi-Ariga, S. M. M., and Ariga,
      H. (1998) J. Biol. Chem. 273, 29794-29800). To clarify the molecular mechanisms
      of MM-1 toward c-Myc, cDNAs encoding MM-1-binding proteins were screened by the
      two-hybrid method with MM-1 as a bait using a human HeLa cDNA library, and a cDNA
      encoding TIF1 beta/KAP1, a transcriptional corepressor, was obtained. MM-1 was
      found to bind to the central portion of TIF1 beta in vitro and in vivo, and these
      proteins were found to be colocalized in the nucleus. MM-1 and TIF1 beta complex
      in human HeLa cells was found to also contain c-Myc, mSin3, and HDAC1.
      Introduction of the C-terminal half of TIF1 beta as a dominant negative form
      abrogated the inhibitory activity of MM-1 toward c-Myc and greatly stimulated the
      transcription activity of c-Myc. Moreover, the inhibitory activity of MM-1 toward
      c-Myc was canceled by trichostatin A, an inhibitor of HDAC1. These results
      indicate that MM-1 is a connecting factor that forms a novel transcription
      repression pathway of c-Myc.

PMID- 11585819
TI  - Binding and partial denaturing of G-quartet DNA by Cdc13p of Saccharomyces
      cerevisiae.
AB  - The protein Cdc13p binds telomeres in vivo and is essential for the maintenance
      of the telomeres of Saccharomyces cerevisiae. In addition, Cdc13p is known to
      bind single-stranded TG(1-3) DNA in vitro. Here we have shown that Cdc13p also
      binds DNA quadruplex, G-quartet, formed by TG(1-3) DNA. Moreover, the binding of
      Cdc13p causes a partial denaturing of the G-quartet DNA. Formation of DNA
      quadruplexes may involve the intermolecular association of TG(1-3) DNA and
      inhibit the extension of telomeres by telomerase. Thus, our finding suggests that
      Cdc13p may disrupt telomere association and facilitate telomere replication.

PMID- 11585820
TI  - In vitro selection of membrane-spanning leucine zipper protein-protein
      interaction motifs using POSSYCCAT.
AB  - A membrane-spanning heptad repeat motif mediates interaction between
      transmembrane segments. This motif was randomized with three different sets of
      mostly hydrophobic residues in the context of POSSYCCAT, a modified ToxR
      transcription activator system. The resulting combinatorial libraries were
      subjected to different levels of selective pressure to obtain groups of
      transmembrane segments that are distinguished by their ability to self-interact
      in bacterial membranes. Upon relating self-interaction to amino acid composition,
      the following conclusions were made. First, randomization with only Leu, Ile,
      Val, Met, and Phe resulted in unexpected robust self-interaction with little
      sequence specificity. Second, with more complex amino acid mixtures that
      represent natural transmembrane segments more closely, self-interaction
      critically depended on amino acid composition of the interface. Whereas the
      contents of Ile and Leu residues increased with the ability to self-interact, the
      contents of Pro and Arg residues decreased. Third, heptad repeat motifs composed
      of Leu, Ile, Val, Met, and Phe were approximately 40-fold over-represented in
      transmembrane segments of single-span membrane proteins as compared with motifs
      composed of the more complex amino acid mixtures. This suggests that heptad
      motifs composed of the smaller subset of amino acids were enriched in the course
      of natural single-span membrane protein evolution.

PMID- 11585821
TI  - Mutational and computational analysis of the alpha(1b)-adrenergic receptor.
      Involvement of basic and hydrophobic residues in receptor activation and G
      protein coupling.
AB  - To investigate their role in receptor coupling to G(q), we mutated all basic
      amino acids and some conserved hydrophobic residues of the cytosolic surface of
      the alpha(1b)-adrenergic receptor (AR). The wild type and mutated receptors were
      expressed in COS-7 cells and characterized for their ligand binding properties
      and ability to increase inositol phosphate accumulation. The experimental results
      have been interpreted in the context of both an ab initio model of the alpha(1b)
      AR and of a new homology model built on the recently solved crystal structure of
      rhodopsin. Among the twenty-three basic amino acids mutated only mutations of
      three, Arg(254) and Lys(258) in the third intracellular loop and Lys(291) at the
      cytosolic extension of helix 6, markedly impaired the receptor-mediated inositol
      phosphate production. Additionally, mutations of two conserved hydrophobic
      residues, Val(147) and Leu(151) in the second intracellular loop had significant
      effects on receptor function. The functional analysis of the receptor mutants in
      conjunction with the predictions of molecular modeling supports the hypothesis
      that Arg(254), Lys(258), as well as Leu(151) are directly involved in receptor-G
      protein interaction and/or receptor-mediated activation of the G protein. In
      contrast, the residues belonging to the cytosolic extensions of helices 3 and 6
      play a predominant role in the activation process of the alpha(1b)-AR. These
      findings contribute to the delineation of the molecular determinants of the
      alpha(1b)-AR/G(q) interface.

PMID- 11585823
TI  - Mitochondrial and cytosolic isoforms of yeast fumarase are derivatives of a
      single translation product and have identical amino termini.
AB  - We have previously proposed that a single translation product of the FUM1 gene
      encoding fumarase is distributed between the cytosol and mitochondria of
      Saccharomyces cerevisiae and that all fumarase translation products are targeted
      and processed in mitochondria before distribution. Alternative models for
      fumarase distribution have been proposed that require more than one translation
      product. In the current work (i) we show by using sequential Edman degradation
      and mass spectrometry that fumarase cytosolic and mitochondrial isoenzymes have
      an identical amino terminus that is formed by cleavage by the mitochondrial
      processing peptidase, (ii) we have generated fumarase mutants in which the second
      potential translation initiation codon (Met-24) has been substituted, yet the
      protein is processed efficiently and retains its ability to be distributed
      between the cytosol and mitochondria, and (iii) we show that although a signal
      peptide is required for fumarase targeting to mitochondria the specific fumarase
      signal peptide and the sequence immediately downstream to the cleavage site are
      not required for the dual distribution phenomenon. Our results are discussed in
      light of our model of fumarase targeting and distribution that suggests rapid
      folding into an import-incompetent state and retrograde movement of the processed
      protein back to the cytosol through the translocation pore.

PMID- 11585822
TI  - Cholesterol depletion inhibits epidermal growth factor receptor transactivation
      by angiotensin II in vascular smooth muscle cells: role of cholesterol-rich
      microdomains and focal adhesions in angiotensin II signaling.
AB  - Angiotensin II (Ang II) induces transactivation of the epidermal growth factor
      (EGF) receptor (EGF-R), which serves as a scaffold for various signaling
      molecules in vascular smooth muscle cells (VSMCs). Cholesterol and sphingomyelin
      enriched lipid rafts are plasma membrane microdomains that concentrate various
      signaling molecules. Caveolae are specialized lipid rafts that are organized by
      the cholesterol-binding protein, caveolin, and have been shown to be associated
      with EGF-Rs. Angiotensin II stimulation promotes a rapid movement of AT(1)
      receptors to caveolae; however, their functional role in angiotensin II signaling
      has not been elucidated. Here we show that cholesterol depletion by beta
      cyclodextrin disrupts caveolae structure and concomitantly inhibits tyrosine
      phosphorylation of the EGF-R and subsequent activation of protein kinase B
      (PKB)/Akt induced by angiotensin II. Similar inhibitory effects were obtained
      with other cholesterol-binding agents, filipin and nystatin. In contrast, EGF-R
      autophosphorylation and activation of Akt/PKB in response to EGF are not affected
      by cholesterol depletion. The early Ang II-induced upstream signaling events
      responsible for transactivation of the EGF-R, such as the intracellular Ca(2+)
      increase and c-Src activation, also remain intact. The EGF-R initially binds
      caveolin, but these two proteins rapidly dissociate following angiotensin II
      stimulation during the time when EGF-R transactivation is observed. The activated
      EGF-R is localized in focal adhesions together with tyrosine-phosphorylated
      caveolin. These findings suggest that 1) a scaffolding role of caveolin is
      essential for EGF-R transactivation by angiotensin II and 2) cholesterol-rich
      microdomains as well as focal adhesions are important signal-organizing
      compartments required for the spatial and temporal organization of angiotensin II
      signaling in VSMCs.

PMID- 11585824
TI  - Copper-induced proteolysis of the CopZ copper chaperone of Enterococcus hirae.
AB  - The cop operon is a key element of copper homeostasis in Enterococcus hirae. It
      encodes two copper ATPases, CopA and CopB, the CopY repressor, and the CopZ
      metallochaperone. It was previously shown that the transcription of the operon is
      induced by copper. The concomitant increase in the levels of Cop proteins,
      particularly the CopB copper export ATPase, allows uncompromised growth of E.
      hirae in up to 5 mm ambient copper. We here show by Western blotting that the
      steady-state level of CopZ was increased only up to 0.5 mm copper. At higher
      copper concentrations, the level of CopZ was decreased and became undetectable at
      5 mm media copper. When CopZ was overexpressed from a plasmid, the cells
      exhibited increased sensitivity to copper and oxidative stress, suggesting that
      high CopZ expression could become toxic to cells. In wild-type cells, the level
      of mRNA transcripts from the cop operon remained high in up to 5 mm copper,
      suggesting that CopZ was proteolyzed. Cell extracts were found to contain a
      copper-activated proteolytic activity that degraded CopZ in vitro. In this assay,
      Cu-CopZ was more susceptible to degradation than apo-CopZ. The growth of E. hirae
      in copper increased the copper-inducible proteolytic activity in extracts.
      Zymographic studies showed the presence of a copper-dependent protease in crude
      cell lysates. Thus, copper-stimulated proteolysis plays an important role in the
      regulation of copper homeostasis in E. hirae.

PMID- 11585825
TI  - Syndecan-4 deficiency leads to high mortality of lipopolysaccharide-injected
      mice.
AB  - Syndecan-4 is a transmembrane heparan sulfate proteoglycan belonging to the
      syndecan family. Following intraperitoneal injection of lipopolysaccharide (LPS),
      syndecan-4-deficient mice exhibited high mortality compared with wild-type
      controls. Severe endotoxin shock was observed in the deficient mice: systolic
      blood pressure and left ventricular fractional shortening were lower in the
      deficient mice than in the wild-type controls 9 h after LPS injection. Although
      histological examinations revealed no apparent differences between two groups,
      the plasma level of interleukin (IL)-1beta was higher in the deficient mice than
      in the wild-type controls 9 h after LPS injection. Consistent with the regulatory
      roles of syndecan-4, its expression in monocytes and endothelial cells of
      microvasculature increased in the wild-type mice after LPS administration.
      Although IL-1beta was produced to the same extent by macrophages from syndecan-4
      deficient and wild-type mice after LPS stimulation, inhibition of its production
      by transforming growth factor-beta1 was impaired in the syndecan-4-deficient
      macrophages. These results indicate that syndecan-4 could be involved in
      prevention of endotoxin shock, at least partly through the inhibitory action of
      transforming growth factor-beta1 on IL-1beta production.

PMID- 11585826
TI  - Biochemical and kinetic analysis of the RNase active sites of the
      integrase/tyrosine family site-specific DNA recombinases.
AB  - In this study, we have used multiple strategies to characterize the mechanisms of
      the type I and type II RNA cleavage activities harbored by the Flp (pronounced
      here as "flip") site-specific DNA recombinase (Flp-RNase I and II, respectively).
      Reactions using half-sites pre-bound by step-arrest mutants of Flp agree with a
      "shared active site" being responsible for the type I reaction (as is the case
      with normal DNA recombination). In a "pre-cleaved" type I substrate containing a
      3'-phosphotyrosyl bond, the Flp-RNase I activity can be elicited by either wild
      type Flp or by Flp(Y343F). Kinetic analyses of the type I reaction are consistent
      with the above observations and support the notion that the DNA recombinase and
      type I RNase active sites are identical. The type II RNase activity is expressed
      by Flp(Y343F) in a half-site substrate and is unaffected by the catalytic
      constitution of a Flp monomer present on a partner half-site. Reaction conditions
      that proscribe the assembly of a DNA bound Flp dimer have no effect on Flp-RNase
      II. These biochemical results, together with kinetic data, are consistent with
      the reaction being performed from a "non-shared active site" contained within a
      single Flp monomer. The Flp-related recombinase Cre, which utilizes a non-shared
      recombination active site, exhibits the type I RNA cleavage reaction. So far, we
      have failed to detect the type II RNase activity in Cre. Despite their
      differences in active site assembly, Cre functionally mimics Flp in being able to
      provide two functional active sites from a trimer of Cre bound to a three-armed
      (Y-shaped) substrate.

PMID- 11585827
TI  - Selective Fe2+-catalyzed oxidative cleavage of gastric H+,K+-ATPase: implications
      for the energy transduction mechanism of P-type cation pumps.
AB  - In the presence of ascorbate/H(2)O(2), Fe(2+) ions or the ATP-Fe(2+) complex
      catalyze selective cleavage of the alpha subunit of gastric H(+),K(+)-ATPase. The
      electrophoretic mobilities of the fragments and dependence of the cleavage
      patterns on E(1) and E(2) conformational states are essentially identical to
      those described previously for renal Na(+),K(+)-ATPase. The cleavage pattern of
      H(+),K(+)-ATPase by Fe(2+) ions is consistent with the existence of two Fe(2+)
      sites: site 1 within highly conserved sequences in the P and A domains, and site
      2 at the cytoplasmic entrance to trans-membrane segments M3 and M1. The change in
      the pattern of cleavage catalyzed by Fe(2+) or the ATP-Fe(2+) complex induced by
      different ligands provides evidence for large conformational movements of the N,
      P, and A cytoplasmic domains of the enzyme. The results are consistent with the
      Ca(2+)-ATPase crystal structure (Protein Data Bank identification code;
      Toyoshima, C., Nakasako, M., Nomura, H., and Ogawa, H. (2000) Nature 405, 647
      655), an E(1)Ca(2+) conformation, and a theoretical model of Ca(2+)-ATPase in an
      E(2) conformation (Protein Data Bank identification code ). Thus, it can be
      presumed that the movements of N, P, and A cytoplasmic domains, associated with
      the E(1) <--> E(2) transitions, are similar in all P-type ATPases. Fe(2+)
      catalyzed cleavage patterns also reveal sequences involved in phosphate, Mg(2+),
      and ATP binding, which have not yet been shown in crystal structures, as well as
      changes which occur in E(1) <--> E(2) transitions, and subconformations induced
      by H(+),K(+)-ATPase-specific ligands such as SCH28080.

PMID- 11585828
TI  - ARM domain-dependent nuclear import of adenomatous polyposis coli protein is
      stimulated by the B56 alpha subunit of protein phosphatase 2A.
AB  - Inactivating mutations in the adenomatous polyposis coli (APC) gene correlate
      with progression of colon cancer and familial adenomatous polyposis. The APC
      tumor suppressor contributes to chromosome segregation and turnover of the
      oncogenic transcriptional activator beta-catenin, and these activities are
      impaired by truncating cancer mutations. APC was recently identified as a
      shuttling protein whose subcellular distribution is regulated by two nuclear
      localization signals (NLSs) and multiple nuclear export signals (NESs). Here, we
      show that mutant disease-linked truncated forms of APC, most of which lack the
      two central NLSs and certain NES sequences, retain nuclear-cytoplasmic shuttling
      activity. Nuclear export of truncated APC is mediated by a dominant N-terminal
      NES. Nuclear import of NLS-deficient APC mutants is facilitated by the N-terminal
      ARM domain. Furthermore, co-expression of the ARM-binding protein, B56 alpha,
      increased the nuclear localization of mutant and wild-type APC. The minimal B56
      alpha-responsive sequence mapped to APC amino acids 302-625. B56 alpha is a
      regulatory subunit of protein phosphatase 2A; however, its ability to shift APC
      to the nucleus was independent of phosphatase activity. We conclude that APC
      nuclear import is regulated by the ARM domain through its interaction with B56
      alpha and postulate that APC/B56 alpha complexes target the dephosphorylation of
      specific proteins within the nucleus.

PMID- 11585829
TI  - Distinct carbohydrate recognition domains of an invertebrate defense molecule
      recognize Gram-negative and Gram-positive bacteria.
AB  - Coelomic fluid of Eisenia foetida earthworms (Oligochaeta, Annelida) contains a
      42-kDa defense molecule named CCF for coelomic cytolytic factor. By binding
      microbial antigens, namely the O-antigen of lipopolysaccharide (LPS), beta-1,3
      glucans, or N,N'-diacetylchitobiose present, respectively, on Gram-negative
      bacteria or yeast cell walls, CCF triggers the prophenoloxidase activating
      pathway. We report that CCF recognizes lysozyme-predigested Gram-positive
      bacteria or the peptidoglycan constituent muramyl dipeptide as well as muramic
      acid. To identify the pattern recognition domains of CCF, deletion mutants were
      tested for their ability to reconstitute the prophenoloxidase cascade in E.
      foetida coelomic fluid depleted of endogenous CCF in the presence of LPS, beta
      1,3-glucans, N,N'-diacetylchitobiose, and muramic acid. In addition, affinity
      chromatography of CCF peptides was performed on immobilized beta-1,3-glucans or
      N,N'-diacetylchitobiose. We found that the broad specificity of CCF for pathogen
      associated molecular patterns results from the presence of two distinct pattern
      recognition domains. One domain, which shows homology with the polysaccharide and
      glucanase motifs of beta-1,3-glucanases and invertebrate defense molecules
      located in the central part of the CCF polypeptide chain, interacts with LPS and
      beta-1,3-glucans. The C-terminal tryptophan-rich domain mediates interactions of
      CCF with N,N'-diacetylchitobiose and muramic acid. These data provide evidence
      for the presence of spatially distinct carbohydrate recognition domains within
      this invertebrate defense molecule.

PMID- 11585830
TI  - Role of the nonspecific DNA-binding region and alpha helices within the core
      domain of retroviral integrase in selecting target DNA sites for integration.
AB  - Retroviral integrase plays an important role in choosing host chromosomal sites
      for integration of the cDNA copy of the viral genome. The domain responsible for
      target site selection has been previously mapped to the central core of the
      protein (amino acid residues 49-238). Chimeric integrases between human
      immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV)
      were prepared to examine the involvement of a nonspecific DNA-binding region
      (residues 213-266) and certain alpha helices within the core domain in target
      site selection. Determination of the distribution and frequency of integration
      events of the chimeric integrases narrowed the target site-specifying motif to
      within residues 49-187 and showed that alpha 3 and alpha 4 helices (residues 123
      166) were not involved in target site selection. Furthermore, the chimera with
      the alpha 2 helix (residues 118-121) of FIV identity displayed characteristic
      integration events from both HIV-1 and FIV integrases. The results indicate that
      the alpha 2 helix plays a role in target site preference as either part of a
      larger or multiple target site-specifying motif.

PMID- 11585831
TI  - The 2-5A/RNase L/RNase L inhibitor (RLI) [correction of (RNI)] pathway regulates
      mitochondrial mRNAs stability in interferon alpha-treated H9 cells.
AB  - Interferon alpha (IFNalpha) belongs to a cytokine family that exhibits antiviral
      properties, immuno-modulating effects, and antiproliferative activity on normal
      and neoplasic cells in vitro and in vivo. IFNalpha exerts antitumor action by
      inducing direct cytotoxicity against tumor cells. This toxicity is at least
      partly due to induction of apoptosis. Although the molecular basis of the
      inhibition of cell growth by IFNalpha is only partially understood, there is a
      direct correlation between the sensitivity of cells to the antiproliferative
      action of IFNalpha and the down-regulation of their mitochondrial mRNAs. Here, we
      studied the role of the 2-5A/RNase L system and its inhibitor RLI in this
      regulation of the mitochondrial mRNAs by IFNalpha. We found that a fraction of
      cellular RNase L and RLI is localized in the mitochondria. Thus, we down
      regulated RNase L activity in human H9 cells by stably transfecting (i) RNase L
      antisense cDNA or (ii) RLI sense cDNA constructions. In contrast to control
      cells, no post-transcriptional down-regulation of mitochondrial mRNAs and no cell
      growth inhibition were observed after IFNalpha treatment in these transfectants.
      These results demonstrate that IFNalpha exerts its antiproliferative effect on H9
      cells at least in part via the degradation of mitochondrial mRNAs by RNase L.

PMID- 11585832
TI  - The conformation of the epsilon- and gamma-subunits within the Escherichia coli
      F(1) ATPase.
AB  - F(1) is the water-soluble portion of the ubiquitous F(1)F(0) ATP synthase. Its
      structure includes three alpha- and three beta-subunits, arranged as a hexameric
      disc, plus a gamma-subunit that penetrates the center of the disc akin to an
      axle. Recently Hausrath et al. (Hausrath, A. C., Gruber, G., Matthews, B. W., and
      Capaldi, R. A. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 13697-13702) obtained
      an electron density map of E. coli F(1) at 4.4-A resolution in which the coiled
      coil alpha-helices of the gamma-subunit could be seen to extend 45 A from the
      base of the alpha(3)beta(3) hexamer. Subsequently the structure of a truncated
      form of the E. coli gamma-subunit in complex with epsilon has been described
      (Rodgers, A. J. W., and Wilce, M. C. J. (2000) Nat. Struct. Biol. 7, 1051-1054).
      In the present study the 4.4-A resolution electron density map of E. coli F(1) is
      re-evaluated in light of the newly available data on the gamma- and epsilon
      subunits. It is shown that the map of the F(1) complex is consistent with the
      structure of the isolated subunits. When E. coli F(1) is compared with that from
      beef heart, the structures of the E. coli gamma- and epsilon-subunits are seen to
      be generally similar to their counterparts in the bovine enzyme but to undergo
      major shifts in position. In particular, the two long, coiled-coil alpha-helices
      that lie along the axis of F(1) both unwind and rotate. Also the epsilon-subunit
      rotates around the axis by 81 degrees and undergoes a net translation of about 23
      A. It is argued that these large-scale changes in conformation reflect distinct
      functional states that occur during the rotation of the gamma-subunit within the
      alpha(3)beta(3) hexamer.

PMID- 11585833
TI  - The major messenger ribonucleoprotein particle protein p50 (YB-1) promotes
      nucleic acid strand annealing.
AB  - p50, a member of the Y-box binding transcription factor family, is tightly
      associated with eukaryotic mRNAs and is responsible for general translational
      regulation. Here we show that p50, in addition to its previously described
      ability to melt mRNA secondary structure, is capable of promoting rapid annealing
      of complementary nucleic acid strands. p50 accelerates annealing of RNA and DNA
      duplexes up to 1500-fold within a wide range of salt concentrations and
      temperatures. Phosphorylation of p50 selectively inhibits DNA annealing.
      Moreover, p50 catalyzes strand exchange between double-stranded and single
      stranded RNAs yielding a product bearing a more extended double-stranded
      structure. Strikingly, p50 displays both RNA-melting and -annealing activities in
      a dose-dependent manner; a relatively low amount of p50 promotes formation of RNA
      duplexes, whereas an excess of p50 causes unwinding of double-stranded forms. Our
      results suggest that the alteration of nucleic acid conformation is a basic
      mechanism of the p50-dependent regulation of gene expression.

PMID- 11585834
TI  - Mechanism for nucleocytoplasmic shuttling of histone deacetylase 7.
AB  - Here we show that HDAC7, a member of the class II histone deacetylases,
      specifically targets several members of myocyte enhancer factors, MEF2A, -2C, and
      -2D, and inhibits their transcriptional activity. Furthermore, we demonstrate
      that DNA-bound MEF2C is capable of recruiting HDAC7, demonstrating that the HDAC7
      dependent repression of transcription is not due to the inhibition of the MEF2
      DNA binding activity. The data also suggest that the promoter bound MEF2 is
      potentially capable of remodeling adjacent nucleosomes via the recruitment of
      HDAC7. We have also observed a nucleocytoplasmic shuttling of HDAC7 and dissected
      the mechanism involved. In NIH3T3 cells, HDAC7 was primarily localized in the
      cytoplasm, essentially due to an active CRM1-dependent export of the protein from
      the nucleus. Interestingly, in HeLa cells, HDAC7 was predominantly nuclear. In
      these cells we could restore the cytoplasmic localization of HDAC7 by expressing
      CaMK I. This CaMK I-induced nuclear export of HDAC7 was abolished when three
      critical serines, Ser-178, Ser-344, and Ser-479, of HDAC7 were mutated. We show
      that these serines are involved in the direct interaction of HDAC7 with 14-3-3.
      Mutations of these serine residues weakened the association with 14-3-3 and
      dramatically enhanced the repression activity of HDAC7 in NIH3T3 cells, but not
      in HeLa cells. Data presented in this work clearly show that the signal dependent
      subcellular localization of HDAC7 is essential in controlling its activities. The
      data also show that the cellular concentration of factors such as 14-3-3, CaMK I,
      and other yet unknown molecules may determine the subcellular localization of an
      individual HDAC member in a cell type and HDAC-specific manner.

PMID- 11585835
TI  - Cyclooxygenase-2 inducing Mcl-1-dependent survival mechanism in human lung
      adenocarcinoma CL1.0 cells. Involvement of phosphatidylinositol 3-kinase/Akt
      pathway.
AB  - Cyclooxygenase 2 (COX-2) has been reported to be commonly expressed in advanced
      stages of human lung adenocarcinoma. In this study, the COX-2 constitutive
      expression vector was transfected into a human lung adenocarcinoma cell line
      CL1.0 and several clones were obtained which stably expressed COX-2. These COX-2
      overexpressed clones demonstrated remarkable resistance to apoptosis induced by
      Ultraviolet B (UVB) irradiation, vinblastine B (VBL) cell lymphoma-2 (Bcl-2), or
      other anti-cancer drugs. To understand how COX-2 prevents apoptosis, the
      investigators examined the expression level of Bcl-2 family members. Mcl-1, but
      not other Bcl-2 members, was significantly up-regulated by COX-2 transfection or
      prostaglandin E(2) (PGE(2)) treatment. Treatment of COX-2-overexpressed cells
      (cox-2/cl.4) with two specific COX-2 inhibitors, NS-398 and celecoxib, caused an
      effective reduction of the increased level of Mcl-1. These data suggest that the
      expression level of Mcl-1 is tightly regulated by COX-2. Moreover, transfection
      of cox-2/cl.4 cells with antisense Mcl-1 enhanced apoptosis induced by UVB
      irradiation, revealing that Mcl-1 plays a crucial role in cell survival activity
      mediated by COX-2. Furthermore, COX-2 transfection or PGE(2) treatment evidently
      activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Inhibition of the
      PI3K pathway by LY294002 or wortmannin effectively attenuated the increased level
      of Mcl-1 induced by COX-2 or PGE(2). Blocking the PI3K activity with a dominant
      negative vector, DN-p85, also greatly diminished the level of Mcl-1 and enhanced
      UVB-elicited cell death in cells transfected by COX-2. In a similar way, LY294002
      inhibited cell survival and Mcl-1 level in PGE(2)-treated CL1.0 cells. These
      findings suggest that COX-2 promotes cell survival by up-regulating the level of
      Mcl-1 by activating the PI3K/Akt-dependent pathway.

PMID- 11585836
TI  - Redox regulation of human Rac1 stability by the proteasome in human aortic
      endothelial cells.
AB  - Rac1 has been shown to activate a NADPH oxidase complex producing superoxide
      anions in a variety of mammalian cell types. We evaluated the impact of Rac1
      induced reactive oxygen species production on the turnover of Rac1 itself in
      human aortic endothelial cells. The concentration of a constitutively active
      mutant of Rac1 (Rac1(V12)) was increased by treatment of the cells with
      diphenylene iodinium (DPI), an inhibitor of the NADPH oxidase. Such an effect was
      not observed for the dominant negative form of Rac1 (Rac1(N17)). We showed a
      decrease in proteolytic degradation of Rac1(V12) in the presence of DPI, and
      showed that short term treatment with H(2)O(2) reverses the effect of DPI. We
      found that proteasome inhibitors (lactacystin and MG132) increased Rac1(V12)
      protein level. In support of this finding, we have identified in the primary
      sequence of Rac1 a potential destruction box domain, which is known to be a
      signal for protein degradation mediated by the ubiquitin/proteasome system. We
      show that Rac1(V12) is ubiquitinated before degradation. By contrast Rac1(N17)
      induces an accumulation of the ubiquitinated form of Rac1. These results suggest
      that Rac1 activation of NADPH oxidase is necessary for the proteolytic
      degradation of Rac1 itself.

PMID- 11585837
TI  - Mammalian sprouty proteins inhibit cell growth and differentiation by preventing
      ras activation.
AB  - Sprouty was genetically identified as an antagonist of fibroblast growth factor
      signaling during tracheal branching in Drosophila. In this study, we provide a
      functional characterization of mammalian Sprouty1 and Sprouty2. Sprouty1 and
      Sprouty2 inhibited events downstream of multiple receptor tyrosine kinases and
      regulated both cell proliferation and differentiation. Using NIH3T3 cell lines
      conditionally expressing Sprouty1 or Sprouty2, we found that these proteins
      specifically inhibit the Ras/Raf/MAP kinase pathway by preventing Ras activation.
      In contrast, activation of the phosphatidylinositol 3-kinase pathway was not
      affected by Sprouty1 or Sprouty2. We further showed that Sprouty1 and Sprouty2 do
      no prevent the formation of a SNT.Grb2.Sos complex upon fibroblast growth factor
      stimulation, yet block Ras activation. Taken together, these results establish
      mammalian Sprouty proteins as important negative regulators of growth factor
      signaling and suggest that Sprouty proteins act downstream of the Grb2.Sos
      complex to selectively uncouple growth factor signals from Ras activation and the
      MAP Kinase pathway.

PMID- 11585838
TI  - SRY interacts with and negatively regulates androgen receptor transcriptional
      activity.
AB  - This study investigated interactions between SRY, the Y chromosome encoded male
      sex determining factor, and the androgen receptor (AR). Coexpression of AR and
      SRY caused marked repression of AR transcriptional activity on a series of
      androgen-responsive reporter genes. Mammalian one- and two-hybrid experiments
      demonstrated an AR-SRY interaction mediated by the AR DNA binding domain.
      Precipitations with glutathione S-transferase fusion proteins indicated that AR
      SRY interactions were direct and mediated by the AR DNA binding domain and the
      SRY high mobility group box DNA binding domain. Transient expression of SRY in
      LNCaP prostate cancer cells repressed expression of an androgen-dependent
      prostate-specific antigen (PSA) reporter gene and stable SRY expression repressed
      the endogenous PSA gene. SRY protein expression was increased by proteosome
      inhibitors and by the androgen-liganded AR in transient and stable transfectants.
      AR transcriptional activity was also repressed by DAX1, and the effects of SRY
      and DAX1 on the AR were additive. These findings indicate that interactions
      between the AR, SRY, and DAX1 contribute to normal male development and function
      and suggest a general role for protein-protein interactions between high mobility
      group box proteins and steroid hormone receptors in regulating tissue-specific
      gene expression.

PMID- 11585839
TI  - Inhibition of transferrin recycling and endosome tubulation by phospholipase A2
      antagonists.
AB  - We report here that a broad spectrum of phospholipase A(2) (PLA(2)) antagonists
      produce a concentration-dependent, differential block in the endocytic recycling
      pathway of transferrin (Tf) and Tf receptors (TfRs) but have no acute affect on
      Tf uptake from the cell surface. At low concentrations of antagonists
      (approximately 1 microm), Tf and TfR accumulated in centrally located recycling
      endosomes, whereas at higher concentrations (approximately 10 microm), Tf-TfR
      accumulated in peripheral sorting endosomes. Several independent lines of
      evidence suggest that this inhibition of recycling may result from the inhibition
      of tubule formation. First, BFA-stimulated endosome tubule formation was
      similarly inhibited by PLA(2) antagonists. Second, endocytosed tracers were found
      in larger spherical endosomes in the presence of PLA(2) antagonists. And third,
      endosome tubule formation in a cell-free, cytosol-dependent reconstitution system
      was equally sensitive PLA(2) antagonists. These results are consistent with the
      conclusion that endosome membrane tubules are formed by the action of a
      cytoplasmic PLA(2) and that PLA(2)-dependent tubules are involved in
      intracellular recycling of Tf and TfR. When taken together with previous studies
      on the Golgi complex, these results also indicate that an intracellular PLA(2)
      activity provides a novel molecular mechanism for inducing tubule formation from
      multiple organelles.

PMID- 11585840
TI  - Targeting of NEDD8 and its conjugates for proteasomal degradation by NUB1.
AB  - NEDD8 is a ubiquitin-like protein that controls vital biological events through
      its conjugation to cullin family members. Recently, we identified a negative
      regulator of the NEDD8 conjugation system, NUB1, which interacts with NEDD8 and
      down-regulates NEDD8 expression post-transcriptionally (Kito, K., Yeh, E. T. H.,
      and Kamitani, T. (2001) J. Biol. Chem. 276, 20603-20609). Here, we show that NUB1
      possesses a ubiquitin-like domain at the N-terminal region and binds to S5a of
      the 19 S proteasome activator (PA700). A GST pull-down assay revealed that the
      overexpression of NUB1 leads to a greater precipitation of NEDD8 conjugates with
      GST-S5a, suggesting that NUB1 might have an adaptor function between S5a and
      NEDD8. Furthermore, proteasome inhibitors completely block NUB1-mediated down
      regulation of NEDD8 expression. These results suggest that NUB1 recruits NEDD8
      and its conjugates to the proteasome for degradation, providing a direct
      functional link between the NEDD8 conjugation system and the proteasomal
      degradation pathway.

PMID- 11585841
TI  - Ubiquinone is necessary for mouse embryonic development but is not essential for
      mitochondrial respiration.
AB  - Ubiquinone (UQ) is a lipid found in most biological membranes and is a co-factor
      in many redox processes including the mitochondrial respiratory chain. UQ has
      been implicated in protection from oxidative stress and in the aging process.
      Consequently, it is used as a dietary supplement and to treat mitochondrial
      diseases. Mutants of the clk-1 gene of the nematode Caenorhabditis elegans are
      fertile and have an increased life span, although they do not produce UQ but
      instead accumulate a biosynthetic intermediate, demethoxyubiquinone (DMQ). DMQ
      appears capable to partially replace UQ for respiration in vivo and in vitro. We
      have produced a vertebrate model of cells and tissues devoid of UQ by generating
      a knockout mutation of the murine orthologue of clk-1 (mclk1). We find that mclk1
      /- embryonic stem cells and embryos accumulate DMQ instead of UQ. As in the
      nematode mutant, the activity of the mitochondrial respiratory chain of -/-
      embryonic stem cells is only mildly affected (65% of wild-type oxygen
      consumption). However, mclk1-/- embryos arrest development at midgestation,
      although earlier developmental stages appear normal. These findings indicate that
      UQ is necessary for vertebrate embryonic development but suggest that
      mitochondrial respiration is not the function for which UQ is essential when DMQ
      is present.

PMID- 11585842
TI  - A single amidotransferase forms asparaginyl-tRNA and glutaminyl-tRNA in Chlamydia
      trachomatis.
AB  - Aminoacyl-tRNA is generally formed by aminoacyl-tRNA synthetases, a family of 20
      enzymes essential for accurate protein synthesis. However, most bacteria generate
      one of the two amide aminoacyl-tRNAs, Asn-tRNA or Gln-tRNA, by transamidation of
      mischarged Asp-tRNA(Asn) or Glu-tRNA(Gln) catalyzed by a heterotrimeric
      amidotransferase (encoded by the gatA, gatB, and gatC genes). The Chlamydia
      trachomatis genome sequence reveals genes for 18 synthetases, whereas those for
      asparaginyl-tRNA synthetase and glutaminyl-tRNA synthetase are absent. Yet the
      genome harbors three gat genes in an operon-like arrangement (gatCAB). We
      reasoned that Chlamydia uses the gatCAB-encoded amidotransferase to generate both
      Asn-tRNA and Gln-tRNA. C. trachomatis aspartyl-tRNA synthetase and glutamyl-tRNA
      synthetase were shown to be non-discriminating synthetases that form the
      misacylated tRNA(Asn) and tRNA(Gln) species. A preparation of pure heterotrimeric
      recombinant C. trachomatis amidotransferase converted Asp-tRNA(Asn) and Glu
      tRNA(Gln) into Asn-tRNA and Gln-tRNA, respectively. The enzyme used glutamine,
      asparagine, or ammonia as amide donors in the presence of either ATP or GTP.
      These results suggest that C. trachomatis employs the dual specificity gatCAB
      encoded amidotransferase and 18 aminoacyl-tRNA synthetases to create the complete
      set of 20 aminoacyl-tRNAs.

PMID- 11585843
TI  - Advances in proteome analysis by mass spectrometry.

PMID- 11585844
TI  - Dynamic protein complexes: insights from mass spectrometry.

PMID- 11585845
TI  - Carbohydrate-modifying sulfotransferases: structure, function, and
      pathophysiology.

PMID- 11585846
TI  - The story of glutamine synthetase regulation.

PMID- 11585847
TI  - Water permeability of asymmetric planar lipid bilayers: leaflets of different
      composition offer independent and additive resistances to permeation.
AB  - To understand how plasma membranes may limit water flux, we have modeled the
      apical membrane of MDCK type 1 cells. Previous experiments demonstrated that
      liposomes designed to mimic the inner and outer leaflet of this membrane
      exhibited 18-fold lower water permeation for outer leaflet lipids than inner
      leaflet lipids (Hill, W.G., and M.L. Zeidel. 2000. J. Biol. Chem. 275:30176
      30185), confirming that the outer leaflet is the primary barrier to permeation.
      If leaflets in a bilayer resist permeation independently, the following equation
      estimates single leaflet permeabilities: 1/P(AB) = 1/P(A) + 1/P(B) (Eq. l), where
      P(AB) is the permeability of a bilayer composed of leaflets A and B, P(A) is the
      permeability of leaflet A, and P(B) is the permeability of leaflet B. Using for
      the MDCK leaflet-specific liposomes gives an estimated value for the osmotic
      water permeability (P(f)) of 4.6 x 10(-4) cm/s (at 25 degrees C) that correlated
      well with experimentally measured values in intact cells. We have now constructed
      both symmetric and asymmetric planar lipid bilayers that model the MDCK apical
      membrane. Water permeability across these bilayers was monitored in the immediate
      membrane vicinity using a Na+-sensitive scanning microelectrode and an osmotic
      gradient induced by addition of urea. The near-membrane concentration
      distribution of solute was used to calculate the velocity of water flow (Pohl,
      P., S.M. Saparov, and Y.N. Antonenko. 1997. Biophys. J. 72:1711-1718). At 36
      degrees C, P(f) was 3.44 +/- 0.35 x 10(-3) cm/s for symmetrical inner leaflet
      membranes and 3.40 +/- 0.34 x 10(-4) cm/s for symmetrical exofacial membranes.
      From, the estimated permeability of an asymmetric membrane is 6.2 x 10(-4) cm/s.
      Water permeability measured for the asymmetric planar bilayer was 6.7 +/- 0.7 x
      10(-4) cm/s, which is within 10% of the calculated value. Direct experimental
      measurement of P(f) for an asymmetric planar membrane confirms that leaflets in a
      bilayer offer independent and additive resistances to water permeation and
      validates the use of.

PMID- 11585848
TI  - Mutations within the P-loop of Kir6.2 modulate the intraburst kinetics of the ATP
      sensitive potassium channel.
AB  - The ATP-sensitive potassium (K(ATP)) channel exhibits spontaneous bursts of rapid
      openings, which are separated by long closed intervals. Previous studies have
      shown that mutations at the internal mouth of the pore-forming (Kir6.2) subunit
      of this channel affect the burst duration and the long interburst closings, but
      do not alter the fast intraburst kinetics. In this study, we have investigated
      the nature of the intraburst kinetics by using recombinant Kir6.2/SUR1 K(ATP)
      channels heterologously expressed in Xenopus oocytes. Single-channel currents
      were studied in inside-out membrane patches. Mutations within the pore loop of
      Kir6.2 (V127T, G135F, and M137C) dramatically affected the mean open time
      (tau(o)) and the short closed time (tauC1) within a burst, and the number of
      openings per burst, but did not alter the burst duration, the interburst closed
      time, or the channel open probability. Thus, the V127T and M137C mutations
      produced longer tau(o), shorter tauC1, and fewer openings per burst, whereas the
      G135F mutation had the opposite effect. All three mutations also reduced the
      single-channel conductance: from 70 pS for the wild-type channel to 62 pS
      (G135F), 50 pS (M137C), and 38 pS (V127T). These results are consistent with the
      idea that the K(ATP) channel possesses a gate that governs the intraburst
      kinetics, which lies close to the selectivity filter. This gate appears to be
      able to operate independently of that which regulates the long interburst
      closings.

PMID- 11585849
TI  - Effects of dantrolene on steps of excitation-contraction coupling in mammalian
      skeletal muscle fibers.
AB  - The effects of the muscle relaxant dantrolene on steps of excitation-contraction
      coupling were studied on fast twitch muscles of rodents. To identify the site of
      action of the drug, single fibers for voltage-clamp measurements, heavy SR
      vesicles for calcium efflux studies and solubilized SR calcium release
      channels/RYRs for lipid bilayer studies were isolated. Using the double Vaseline
      gap or the silicone-clamp technique, dantrolene was found to suppress the
      depolarization-induced elevation in intracellular calcium concentration ([Ca2+]i)
      by inhibiting the release of calcium from the SR. The suppression of [Ca2+]i was
      dose-dependent, with no effect at or below 1 microM and a 53 +/- 8% (mean +/-
      SEM, n = 9, cut fibers) attenuation at 0 mV with 25 microM of extracellularly
      applied dantrolene. The drug was not found to be more effective if injected than
      if applied extracellularly. Calculating the SR calcium release revealed an equal
      suppression of the steady (53 +/- 8%) and of the early peak component (46 +/-
      6%). The drug did not interfere with the activation of the voltage sensor in as
      much as the voltage dependence of both intramembrane charge movements and the L
      type calcium currents (I(Ca)) were left, essentially, unaltered. However, the
      inactivation of I(Ca) was slowed fourfold, and the conductance was reduced from
      200 +/- 16 to 143 +/- 8 SF(-1) (n = 10). Dantrolene was found to inhibit thymol
      stimulated calcium efflux from heavy SR vesicles by 44 +/- 10% (n = 3) at 12
      microM. On the other hand, dantrolene failed to affect the isolated RYR
      incorporated into lipid bilayers. The channel displayed a constant open
      probability for as long as 30-50 min after the application of the drug. These
      data locate the binding site for dantrolene to be on the SR membrane, but be
      distinct from the purified RYR itself.

PMID- 11585850
TI  - Prolongation of actions of Ca2+ early in phototransduction by 9-demethylretinal.
AB  - During adaptation Ca2+ acts on a step early in phototransduction, which is
      normally available for only a brief period after excitation. To investigate the
      identity of this step, we studied the effect of the light-induced decline in
      intracellular Ca2+ concentration on the response to a bright flash in normal
      rods, and in rods bleached and regenerated with 11-cis 9-demethylretinal, which
      forms a photopigment with a prolonged photoactivated lifetime. Changes in
      cytoplasmic Ca2+ were opposed by rapid superfusion of the outer segment with a
      0Na+/0Ca2+ solution designed to minimize Ca2+ fluxes across the surface membrane.
      After regeneration of a bleached rod with 9-demethlyretinal, the response in
      Ringer's to a 440-nm bright flash was prolonged in comparison with the unbleached
      control, and the response remained in saturation for 10-15s. If the dynamic fall
      in Ca2+i induced by the flash was delayed by stepping the outer segment to
      0Na+/0Ca2+ solution just before the flash and returning it to Ringer's shortly
      before recovery, then the response saturation was prolonged further, increasing
      linearly by 0.41 +/- 0.01 of the time spent in this solution. In contrast, even
      long exposures to 0Na+/0Ca2+ solution of rods containing native photopigment
      evoked only a modest response prolongation on the return to Ringer's.
      Furthermore, if the rod was preexposed to steady subsaturating light, thereby
      reducing the cytoplasmic calcium concentration, then the prolongation of the
      bright flash response evoked by 0Na+/0Ca2+ solution was reduced in a graded
      manner with increasing background intensity. These results indicate that altering
      the chromophore of rhodopsin prolongs the time course of the Ca2+-dependent step
      early in the transduction cascade so that it dominates response recovery, and
      suggest that it is associated with photopigment quenching by phosphorylation.

PMID- 11585851
TI  - Regulation of cloned ATP-sensitive K channels by adenine nucleotides and
      sulfonylureas: interactions between SUR1 and positively charged domains on
      Kir6.2.
AB  - K(ATP) channels, comprised of the pore-forming protein Kir6.x and the
      sulfonylurea receptor SURx, are regulated in an interdependent manner by adenine
      nucleotides, PIP2, and sulfonylureas. To gain insight into these interactions, we
      investigated the effects of mutating positively charged residues in Kir6.2,
      previously implicated in the response to PIP2, on channel regulation by adenine
      nucleotides and the sulfonylurea glyburide. Our data show that the Kir6.2 "PIP2
      insensitive" mutants R176C and R177C are not reactivated by MgADP after ATP
      induced inhibition and are also insensitive to glyburide. These results suggest
      that R176 and R177 are required for functional coupling to SUR1, which confers
      MgADP and sulfonylurea sensitivity to the K(ATP) channel. In contrast, the R301C
      and R314C mutants, which are also "PIP2-insensitive," remained sensitive to
      stimulation by MgADP in the absence of ATP and were inhibited by glyburide. Based
      on these findings, as well as previous data, we propose a model of the K(ATP)
      channel whereby in the presence of ATP, the R176 and R177 residues on Kir6.2 form
      a specific site that interacts with NBF1 bound to ATP on SUR1, promoting channel
      opening by counteracting the inhibition by ATP. This interaction is facilitated
      by binding of MgADP to NBF2 and blocked by binding of sulfonylureas to SUR1. In
      the absence of ATP, since K(ATP) channels are not blocked by ATP, they do not
      require the counteracting effect of NBF1 interacting with R176 and R177 to open.
      Nevertheless, channels in this state remain activated by MgADP. This effect may
      be explained by a direct stimulatory interaction of NBF2/MgADP moiety with
      another region of Kir6.2 (perhaps the NH2 terminus), or by NBF2/MgADP still
      promoting a weak interaction between NBF1 and Kir6.2 in the absence of ATP. The
      region delimited by R301 and R314 is not involved in the interaction with NBF1 or
      NBF2, but confers additional PIP2 sensitivity.

PMID- 11585852
TI  - CFTR: covalent and noncovalent modification suggests a role for fixed charges in
      anion conduction.
AB  - The goal of the experiments described here was to explore the possible role of
      fixed charges in determining the conduction properties of CFTR. We focused on
      transmembrane segment 6 (TM6) which contains four basic residues (R334, K335,
      R347, and R352) that would be predicted, on the basis of their positions in the
      primary structure, to span TM6 from near the extracellular (R334, K335) to near
      the intracellular (R347, R352) end. Cysteines substituted at positions 334 and
      335 were readily accessible to thiol reagents, whereas those at positions 347 and
      352 were either not accessible or lacked significant functional consequences when
      modified. The charge at positions 334 and 335 was an important determinant of
      CFTR channel function. Charge changes at position 334--brought about by covalent
      modification of engineered cysteine residues, pH titration of cysteine and
      histidine residues, and amino acid substitution--produced similar effects on
      macroscopic conductance and the shape of the I-V plot. The effect of charge
      changes at position 334 on conduction properties could be described by
      electrodiffusion or rate-theory models in which the charge on this residue lies
      in an external vestibule of the pore where it functions to increase the
      concentration of Cl adjacent to the rate-limiting portion of the conduction path.
      Covalent modification of R334C CFTR increased single-channel conductance
      determined in detached patches, but did not alter open probability. The results
      are consistent with the hypothesis that in wild-type CFTR, R334 occupies a
      position where its charge can influence the distribution of anions near the mouth
      of the pore.

PMID- 11585854
TI  - Donepezil hydrochloride preserves regional cerebral blood flow in patients with
      Alzheimer's disease.
AB  - The aim of this SPECT study was to investigate the effects of donepezil on
      regional cerebral blood flow (rCBF) in patients with mild to moderate Alzheimer's
      disease (AD) using statistical parametric mapping. METHODS: rCBF was
      noninvasively measured using (99m)Tc-ethyl cysteinate dimer in 35 AD patients
      with a Mini-Mental State Examination score > 16 on initial evaluation. Baseline
      and follow-up SPECT studies with a mean interval of 12 mo were performed on these
      patients. We used the adjusted rCBF images in the relative flow distribution
      (normalization of global cerebral blood flow for each patient to 50 mL/100 g/min
      with proportional scaling) to compare these groups through statistical parametric
      mapping. RESULTS: In the follow-up study, the adjusted rCBF was significantly
      preserved in the right and left anterior cingulate gyri, right middle temporal
      gyrus, right inferior parietal lobules, and prefrontal cortex of donepezil
      treated AD patients, compared with placebo-treated AD patients. CONCLUSION:
      Treatment with donepezil for 1 y appears to reduce the decline in rCBF,
      suggesting preservation of functional brain activity.

PMID- 11585853
TI  - CFTR: covalent modification of cysteine-substituted channels expressed in Xenopus
      oocytes shows that activation is due to the opening of channels resident in the
      plasma membrane.
AB  - Some studies of CFTR imply that channel activation can be explained by an
      increase in open probability (P(o)), whereas others suggest that activation
      involves an increase in the number of CFTR channels (N) in the plasma membrane.
      Using two-electrode voltage clamp, we tested for changes in N associated with
      activation of CFTR in Xenopus oocytes using a cysteine-substituted construct
      (R334C CFTR) that can be modified by externally applied, impermeant thiol
      reagents like [2-(trimethylammonium)ethyl] methanethiosulfonate bromide (MTSET+).
      Covalent modification of R334C CFTR with MTSET+ doubled the conductance and
      changed the I-V relation from inward rectifying to linear and was completely
      reversed by 2-mercaptoethanol (2-ME). Thus, labeled and unlabeled channels could
      be differentiated by noting the percent decrease in conductance brought about by
      exposure to 2-ME. When oocytes were briefly (20 s) exposed to MTSET+ before CFTR
      activation, the subsequently activated conductance was characteristic of labeled
      R334C CFTR, indicating that the entire pool of CFTR channels activated by cAMP
      was accessible to MTSET+. The addition of unlabeled, newly synthesized channels
      to the plasma membrane could be monitored on-line during the time when the rate
      of addition was most rapid after cRNA injection. The addition of new channels
      could be detected as early as 5 h after cRNA injection, occurred with a half time
      of approximately 24-48 h, and was disrupted by exposing oocytes to Brefeldin A,
      whereas activation of R334C CFTR by cAMP occurred with a half time of tens of
      minutes, and did not appear to involve the addition of new channels to the plasma
      membrane. These findings demonstrate that in Xenopus oocytes, the major mechanism
      of CFTR activation by cAMP is by means of an increase in the open probability of
      CFTR channels.

PMID- 11585855
TI  - Fractal analysis of cerebral blood flow distribution in Alzheimer's disease.
AB  - This study describes a method for quantifying cerebral blood flow (CBF)
      distribution in Alzheimer's disease (AD) from SPECT images obtained with (99m)Tc
      hexamethylpropyleneamine oxime (HMPAO) by 3-dimensional fractal analysis (3D-FA).
      METHODS: HMPAO SPECT was performed on 68 patients with probable AD and 14 healthy
      control subjects. We delineated the CBF images using 4 cutoff levels (35%, 40%,
      45%, and 50% of the maximal voxel radioactivity) and measured the total number of
      voxels in the areas surrounded by the contours obtained with each cutoff level.
      We calculated fractal dimensions from the relationship between the total number
      of voxels and the cutoff levels transformed into natural logarithms. RESULTS: The
      fractal dimensions (mean +/- SD) for patients with probable AD and healthy
      subjects were 0.74 +/- 0.33 and 0.52 +/- 0.09, respectively. A significant
      difference in the fractal dimension was found between groups (P = 0.001).
      Statistically significant correlations were obtained between the fractal
      dimension and the Mini-Mental State Examination score (r = -0.598; P < 0.0001)
      and between the fractal dimension and the AD Assessment Scale (r = 0.670; P <
      0.0001). The fractal dimensions for subjects with clinical dementia rates (CDRs)
      of 0, 1, 2, and 3 were 0.52 +/- 0.09, 0.63 +/- 0.21, 0.77 +/- 0.23 (P < 0.05 vs.
      the group with a CDR of 1), and 1.43 +/- 0.49 (P < 0.0001 vs. the group with a
      CDR of 2), respectively. CONCLUSION: Quantification of CBF distribution on SPECT
      images in AD was possible using 3D-FA. The fractal dimension was well correlated
      with the cognitive impairment, as assessed in neuropsychologic tests. 3D-FA may
      be a useful method for objectively evaluating the progression of AD.

PMID- 11585856
TI  - Clinical impact of combination of scatter, attenuation correction, and depth
      dependent resolution recovery for (201)Tl studies.
AB  - A lack of specificity for myocardial perfusion imaging has been widely reported,
      mostly related to false-positive defects on the inferior wall. The application of
      depth-dependent resolution recovery (RR), attenuation correction (AC) using
      external source devices, and scatter correction has been proposed to resolve this
      pitfall. METHODS: We studied the clinical benefit of depth-dependent RR,
      nonuniform AC using a scanning line source, and scatter correction (photon energy
      recovery [PER]) compared with filtered backprojection alone. Eighty-two patients
      were included: 40 healthy volunteers with a low likelihood of coronary artery
      disease (control group) and 42 patients with proven right or circumflex coronary
      artery disease but without involvement of the left anterior descending artery.
      Among these 82 patients, the images of 33 were also processed with PER. RESULTS:
      RR did not alter the performance of filtered backprojection alone. AC + RR
      greatly improved specificity and the rate of normal (201)Tl SPECT findings in the
      control population (from 56% to 95% and from 53% to 100%, respectively) but
      significantly decreased sensitivity (from 92% to 54%). AC + RR generated a false
      anteroapical defect in 21% of patients and reverse redistribution of the apex in
      23%. AC + RR significantly decreased the extent of the stress defect (from 4.09
      to 3.21 segments, P < 0.003) and increased the perfusion score of the stress
      defect (from 0.78 +/- 0.72 to 1.47 +/- 1.11, P < 0.00061). Moreover, AC + RR
      generated overcorrection on the inferior wall, leading to false estimation of
      viability for 11 of 15 patients with an old inferior myocardial scar without
      evidence of residual viability. PER decreased overcorrection on the inferior
      wall, but without improving sensitivity. PER did not significantly reduce the
      number of anteroapical false-positives or the number of apical reverse
      distribution cases. CONCLUSION: AC + RR improved the specificity and normalcy
      rate of (201)Tl SPECT myocardial perfusion imaging but generated overcorrection
      on the inferior wall, leading to low sensitivity and to false evaluation of
      myocardial viability in 73% of the patients with inferior infarction. AC + RR
      also generated anteroapical artifacts. The addition of scatter correction did not
      significantly reduce these drawbacks.

PMID- 11585857
TI  - (99m)Tc-sestamibi retention characteristics during pharmacologic hyperemia in
      human myocardium: comparison with coronary flow reserve measured by Doppler
      flowire.
AB  - The aim of the study was to investigate the increase in myocardial (99m)Tc
      methoxyisobutylisonitrile (sestamibi) retention in humans during pharmacologic
      vasodilation. METHODS: For calculation of the increase in (99m)Tc-sestamibi
      retention during hyperemia, baseline and adenosine triphosphate (ATP)-induced
      hyperemic stress sestamibi studies were performed using a same-day rest-stress
      protocol. On the injection of sestamibi, left ventricular dynamic data were
      obtained for 90 s. The increase in sestamibi retention from baseline to hyperemia
      was calculated by the formula [abstract: see text] where Cm(h)(t) and Cm(b)(t)
      are myocardial counts on the tomographic image, and Cb(b)(tau) and Cb(h)(tau) are
      the left ventricular blood-pool counts during the first transit of sestamibi at
      baseline and during hyperemia, respectively. Coronary flow increase during
      intravenous ATP stress was measured using intracoronary Doppler flow guide wire
      and compared with the scintigraphic results of 28 measurements in 22 patients.
      RESULTS: Sestamibi retention increased as coronary flow velocity increased but
      plateaued at >2.5-3 times baseline flow velocity. The relationship between the
      increase in sestamibi retention (Y) and the increase in flow (X) is expressed as
      follows: Y = 0.44 + 0.60X - 0.068X(2) (r = 0.82). CONCLUSION: In humans, the
      increase in (99m)Tc-sestamibi myocardial retention underestimates coronary flow
      reserve, particularly at high flow rates. Knowledge of these tracer retention
      characteristics will contribute to a more comprehensive understanding of the
      manner and interpretation of stress sestamibi imaging.

PMID- 11585858
TI  - Clinical impact of (18)F-FDG PET in thyroid carcinoma patients with elevated
      thyroglobulin levels and negative (131)I scanning results after therapy.
AB  - 18F-FDG PET has been shown to effectively detect differentiated thyroid carcinoma
      (DTC) metastases with impaired iodine-trapping ability. This article evaluates
      the potential contribution of FDG PET in the follow-up of patients with
      differentiated thyroid carcinoma, elevated thyroglobulin (Tg) levels, and
      negative whole-body scan results obtained after high doses of (131)I. METHODS: We
      prospectively assessed the ability of FDG to detect metastases in 37 DTC patients
      who had undergone total thyroidectomy and radioactive ablation and presented with
      persistent disease, as assessed from elevated Tg levels and negative results of
      whole-body scans performed after therapeutic doses of (131)I. Additional
      conventional imaging procedures were performed to detect residual disease, and
      the patients were divided into 2 groups: group 1, with positive conventional
      imaging findings (n = 10), and group 2, with negative conventional imaging
      findings (n = 27). RESULTS: FDG PET showed positive findings in 28 patients and
      accurately localized tumor sites in 89% of them. In group 1, FDG PET confirmed 17
      of 18 previously known tumor sites and detected 11 additional sites. In group 2,
      FDG PET findings were positive in 19 of 27 patients with no previously detected
      metastases. PET was effective for both low- and high-stage tumors. The FDG data
      led to a change in the clinical management of 29 of 37 patients with further
      surgical resection in 23 patients, 14 of whom achieved disease-free status, and
      external radiation therapy in 4 patients. CONCLUSION: FDG PET is able to detect
      metastases undetected by (131)I posttherapy whole-body scanning in patients with
      elevated Tg levels. It should be proposed as a first-line investigation in
      patients with persistent disease but negative findings on (131)I whole-body scans
      after treatment.

PMID- 11585859
TI  - Serum thyroglobulin concentrations and (131)I whole-body scan results in patients
      with differentiated thyroid carcinoma after administration of recombinant human
      thyroid-stimulating hormone.
AB  - The use of recombinant human thyroid-stimulating hormone (rhTSH) has recently
      become available as an alternative diagnostic tool to assess the persistence and
      recurrence of differentiated thyroid carcinoma (DTC) in patients on thyroid
      hormone-suppressive therapy (THST) after near-total or total thyroidectomy and
      ablative doses of (131)I. We report the results of rhTSH administration in
      patients who were monitored for DTC. METHODS: Thirty-three adult DTC patients (13
      men, 20 women; mean age +/- SE, 45.6 +/- 2.31 y; age range, 21-65 y) underwent
      diagnostic follow-up after rhTSH administration at a dose of 0.9 mg once a day
      for 2 d. Whole-body scanning and serum thyroglobulin (Tg) measurement were
      performed after rhTSH administration. Patients were divided into 2 groups
      depending on serum Tg concentrations on THST: 29 patients had Tg concentrations
      of <2 ng/mL (group A) and 4 patients had Tg values of >2 ng/mL (group B).
      RESULTS: In group A, Tg values remained at <2 ng/mL in 25 patients and increased
      from 1.1 +/- 0.14 ng/mL to 22.0 +/- 5.75 ng/mL (mean +/- SE) in 4 patients after
      rhTSH administration. Whole-body scanning did not reveal any uptake of (131)I in
      the 25 patients without an increase in Tg, whereas (131)I uptake was evident in 2
      of the 4 patients with a rise in Tg. In group B, Tg values increased in all 4
      patients from 17.3 +/- 6.35 ng/mL to 55.3 +/- 12.75 ng/mL, and (131)I uptake was
      evident in 3 of the 4 patients. No major adverse effects were reported after
      rhTSH administration. CONCLUSION: Our results show that the measurement of serum
      Tg concentrations after rhTSH has a higher diagnostic value than whole-body
      scanning in detecting the persistence of thyroid tissue. Therefore, rhTSH should
      be administered in TSH-suppressed patients with basal serum Tg concentrations of
      <2 ng/mL because the increment in serum Tg concentrations may reveal the
      persistence of thyroid tissue in these patients.

PMID- 11585860
TI  - Expression of multidrug resistance protein and messenger RNA correlate with
      (99m)Tc-MIBI imaging in patients with lung cancer.
AB  - In vitro studies have shown that (99m)Tc-sestamibi (MIBI) is a transport
      substrate for the P-glycoprotein (Pgp) pump and the multidrug resistance
      associated protein (MRP) pump. However, whether MRP and lung resistance protein
      (LRP) affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer is not
      known. In this study, we explored whether Pgp and the other pumps, MRP and LRP,
      affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer. METHODS:
      Thirty-four lung cancer patients who underwent surgery were examined. Before
      surgery, (99m)Tc-MIBI SPECT was performed 15 min and 180 min after injection, and
      early uptake, delayed uptake (L/Nd), and washout rate (L/Nwr) of (99m)Tc-MIBI
      were obtained. Pgp, MRP, and LRP expression were investigated by
      immunohistochemistry. The messenger RNA (mRNA) level of Pgp, MRP, and LRP was
      determined by real-time reverse-transcription polymerase chain reaction. The lung
      cancer (99m)Tc-MIBI images were correlated with protein and mRNA expression.
      RESULTS: The mean L/Nd of the Pgp (-) group was significantly higher than that of
      the Pgp (++) group (P = 0.0324). The Pgp (++) group had a higher L/Nwr than did
      the Pgp (-) group (P = 0.0269). The mean L/Nd of the Pgp mRNA low-expression
      group was significantly higher than that of the Pgp mRNA high-expression group (P
      = 0.0127). The Pgp mRNA high-expression group had a higher L/Nwr than did the Pgp
      mRNA low-expression group (P = 0.0825). No appreciable correlation was found
      between the lung cancer (99m)Tc-MIBI images and the expression of MRP or LRP on
      the level of protein or mRNA. CONCLUSION: These data suggest that an increased
      level of Pgp expression correlates with a low accumulation on delayed scans and a
      high L/Nwr of (99m)Tc-MIBI in lung cancer. Neither MRP nor LRP expression on the
      level of either protein or mRNA correlated significantly with tumor accumulation
      or efflux of (99m)Tc-MIBI in lung cancer.

PMID- 11585861
TI  - Determination of glomerular filtration rate by means of newly developed plastic
      scintillation counter both with and without dilution procedures.
AB  - The double-well single-plastic scintillation counter (DW counter) has been
      developed to reduce the need for technical expertise in a plasma sample method
      after a single injection of radioactive marker. The DW counter serves the 2
      functions of a standard well counter in well A and a dose calibrator in well B.
      The aim of this study was to assess the clinical feasibility of the counter for
      the estimation of glomerular filtration rate (GFR) with (99m)Tc
      diethylenetriaminepentaacetic acid (DTPA). METHODS: The study was performed on 25
      patients with varying degrees of renal dysfunction. The GFR was estimated by a
      single-sample method after a single injection of (99m)Tc-DTPA. Total injected
      dose and plasma radioactivity were calculated following 2 methods: standard
      dilution with a single well (dilution method) and no dilution with 2 wells
      (direct method). RESULTS: The GFR directly estimated by the DW counter correlated
      excellently with the GFR estimated by the dilution method (r = 0.998; root mean
      square error = 2.01 mL/min/1.73 m(2)). The 95% of differences (-0.3124 to 0.0423
      percentage injected dose [%ID]/L/1.73 m(2)) in plasma concentration between the 2
      comparative methods was <2 SDs. The direct method tended to give slightly higher
      readings of plasma concentration than did the dilution method (95% confidence
      interval = -0.0364 to -0.0904 %ID/L/1.73 m(2)). CONCLUSION: The DW counter can
      circumvent laborious dilution techniques and expertise required for quantifying
      the GFR in a single-sample method after a single injection of (99m)Tc-DTPA in
      clinical practice. It is proposed as an alternative to the standard dilution
      method.

PMID- 11585862
TI  - Comparison of [(18)F]FDG PET and (201)Tl SPECT in evaluation of pulmonary
      nodules.
AB  - Recent reports have indicated the value of [(18)F]FDG PET and (201)Tl SPECT in
      diagnosing lung cancer. In this study, we compared the diagnostic value of FDG
      PET and (201)Tl SPECT in the evaluation of pulmonary nodules. METHODS: Sixty
      three patients with 66 pulmonary nodules suspected to be lung cancer on the basis
      of chest CT were examined by FDG PET and (201)Tl SPECT (early and delayed scans)
      within a week of each study. For semiquantitative analysis, the standardized
      uptake value (SUV) or the tumor-to-nontumor activity ratio (T/N) (or both) was
      calculated. All of these lesions were completely removed thoracoscopically or by
      thoracotomy and were examined histologically. RESULTS: Fifty-four nodules were
      histologically confirmed to be malignant tumors, and 12 were benign. Both
      techniques delineated focal lesions with an increase in tracer accumulation in 41
      of 54 lung cancers. (201)Tl SPECT on early or delayed scans (or both) identified
      4 additional lung cancers that FDG PET images did not reveal: 3
      bronchioloalveolar carcinomas and a well-differentiated adenocarcinoma. FDG PET
      identified 3 additional lung cancers that (201)Tl SPECT images did not reveal; 2
      of these lung cancers were <2 cm in diameter. The mean FDG SUV and T/N of
      bronchioloalveolar carcinomas (2.06 +/- 0.76 and 3.49 +/- 1.03, respectively)
      were significantly lower than those of poorly differentiated adenocarcinomas
      (5.55 +/- 2.01 [P = 0.026] and 8.23 +/- 2.16 [P = 0.01], respectively). However,
      no significant difference was found in (201)Tl T/N on early and delayed scans
      between bronchioloalveolar carcinomas (1.64 +/- 0.29 and 1.87 +/- 0.42,
      respectively) and poorly differentiated adenocarcinomas (1.58 +/- 0.32 and 2.76
      +/- 1.36, respectively). Of the 12 benign nodules, FDG PET and (201)Tl SPECT
      showed false-positive results for the same 7 benign nodules (58.3%) (4
      granulomas, 1 sarcoidosis, 1 inflammatory pseudotumor, and 1 aspergilloma).
      Negative FDG PET findings and positive (201)Tl SPECT findings were obtained only
      for bronchioloalveolar carcinomas or a well-differentiated adenocarcinoma but not
      for other histologic types of lung cancers or benign pulmonary nodules.
      CONCLUSION: No significant difference was found between FDG PET and (201)Tl SPECT
      in specificity for the differentiation of malignant and benign pulmonary nodules.
      The degree of differentiation of lung adenocarcinoma correlated with FDG uptake
      but not with (201)Tl uptake. Bronchioloalveolar carcinoma (a well-differentiated,
      slow-growing tumor) findings typically were positive with (201)Tl but were
      negative with FDG. The combination of FDG PET and (201)Tl SPECT may provide
      additional information regarding the tissue characterization of pulmonary
      nodules.

PMID- 11585863
TI  - Changing pattern of lung cancer and its imaging: (201)Tl SPECT versus [(18)F]FDG
      PET.

PMID- 11585864
TI  - Technical aspects of myocardial SPECT imaging.
AB  - Myocardial perfusion SPECT imaging accounts for well over 90% of all myocardial
      perfusion imaging performed in the United States today. Although clearly superior
      to the traditional planar technique in terms of image contrast and consequent
      diagnostic and prognostic yield, the SPECT approach also involves additional
      acquisition and processing steps. This article concisely describes the entire
      technical sequence of myocardial SPECT imaging, from the acquisition of
      projection images to their filtration and tomographic reconstruction and
      concluding with reorientation of the tomographic transaxial images. A simplified
      explanation of the frequency, or Fourier, domain and the operation of digital
      filters is also presented to help the reader intuitively understand these
      important concepts.

PMID- 11585865
TI  - High-level production of alpha-particle-emitting (211)At and preparation of
      (211)At-labeled antibodies for clinical use.
AB  - In vitro and in vivo studies in human glioma models suggest that the antitenascin
      monoclonal antibody 81C6 labeled with the 7.2-h-half-life alpha-particle emitter
      (211)At might be a valuable endoradiotherapeutic agent for the treatment of brain
      tumors. The purpose of this study was to develop methods for the production of
      high levels of (211)At and the radiosynthesis of clinically useful amounts of
      (211)At-labeled human/mouse chimeric 81C6 antibody. METHODS: (211)At was produced
      through the (209)Bi(alpha, 2n)(211)At reaction using an internal target system
      and purified by a dry distillation process. Antibody labeling was accomplished by
      first synthesizing N-succinimidyl 3-[(211)At]astatobenzoate from the
      corresponding tri-n-butyl tin precursor and reacting it with the antibody in pH
      8.5 borate buffer. Quality control procedures consisted of methanol
      precipitation, size-exclusion high-performance liquid chromatography (HPLC), and
      pyrogen and sterility assays, as well as determination of the immunoreactive
      fraction by a rapid procedure using a recombinant tenascin fragment coupled to
      magnetic beads. RESULTS: A total of 16 antibody labeling runs were performed.
      Using beam currents of 50-60 microA alpha-particles and irradiation times of 1.5
      4.5 h, the mean (211)At production yield was 27.75 +/- 2.59 MBq/microA.h, and the
      maximum level of (211)At produced was 6.59 GBq after a 4-h irradiation at 55
      microA. The decay-corrected distillation yield was 67% +/- 16%. The yield for the
      coupling of the (211)At-labeled active ester to the antibody was 76% +/- 8%. The
      fraction of (211)At activity that eluted with a retention time corresponding to
      intact IgG on HPLC was 96.0% +/- 2.5%. All preparations had a pyrogen level of
      <0.125 EU/mL and were determined to be sterile. The mean immunoreactive fraction
      for these 16 preparations was 83.3% +/- 5.3%. Radiolysis did not interfere with
      labeling chemistry or the quality of the labeled antibody product. CONCLUSION:
      These results show that it is feasible to produce clinically relevant activities
      of (211)At-labeled antibodies and have permitted the initiation of a phase I
      trial of (211)At-labeled chimeric 81C6 administered directly into the tumor
      resection cavities of brain tumor patients.

PMID- 11585866
TI  - Overcoming the obstacles to clinical evaluation of (211)At-labeled
      radiopharmaceuticals.

PMID- 11585867
TI  - 99mTc-labeled divalent and tetravalent CC49 single-chain Fv's: novel imaging
      agents for rapid in vivo localization of human colon carcinoma.
AB  - Radioimmunopharmaceutical agents enabling rapid high-resolution imaging, high
      tumor-to-background ratios, and minimal immunogenicity are being sought for
      cancer diagnosis and imaging. Genetic engineering techniques have allowed the
      design of single-chain Fv's (scFv's) of monoclonal antibodies (mAbs) recognizing
      tumor-associated antigens. These scFv's show good tumor targeting and
      biodistribution properties in vivo, indicating their potential as imaging agents
      when labeled with a suitable radionuclide. METHODS: Divalent (sc(Fv)(2)) and
      tetravalent ([sc(Fv)(2)](2)) scFv's of mAb CC49 were evaluated for
      radioimmunolocalization of LS-174T colon carcinoma xenografts in athymic mice.
      scFv's were radiolabeled with (99m)Tc by way of the bifunctional chelator
      succinimidyl-6-hydrazinonicotinate hydrochloride using tricine as the
      transchelator. The immunoreactivity and in vitro stability of the scFv's were
      analyzed after radiolabeling. Biodistribution and pharmacokinetic studies were
      performed to determine the tumor-targeting potential of the radiolabeled scFv's.
      Whole-mouse autoradiography illustrated the possible application of these (99m)Tc
      labeled multivalent scFv's for imaging. RESULTS: The radiolabeling procedure gave
      > or =95% radiometal incorporation, with a specific activity of >74 MBq/mg scFv.
      In solid-phase radioimmunoassay, both sc(Fv)(2) and [sc(Fv)(2)](2) exhibited 75%
      85% immunoreactivity, with nonspecific binding between 0.8% and 1.2%. Size
      exclusion high-performance liquid chromatography showed sc(Fv)(2) as a 60-kDa
      protein and [sc(Fv)(2)](2) as a 120-kDa protein. Blood clearance studies showed
      the elimination half-life of (99m)Tc-labeled sc(Fv)(2) as 144 min and that of
      [sc(Fv)(2)](2) as 307 min. Whole-body clearance studies confirmed the rapid
      elimination of scFv's, with half-lives of 184 +/- 19 min for sc(Fv)(2) and 265 +/
      39 min for [sc(Fv)(2)](2) (P < 0.001). At 6 h after administration, the tumor
      localization was 7.2 +/- 0.7 percentage injected dose per gram of tumor (%ID/g)
      for (99m)Tc-sc(Fv)(2). (99m)Tc-[sc(Fv)(2)](2) showed a tumor uptake of 19.1 +/-
      1.1 %ID/g at the same time; the amount of radioactivity in the tumors was 4-fold
      higher than in the spleen and kidneys and 2-fold higher than in the liver.
      Macroautoradiography performed at 6 and 16 h after administration clearly
      detected the tumor with both scFv's. CONCLUSION: (99m)Tc-labeled multivalent
      scFv's show good tumor-targeting characteristics and high radiolocalization
      indices (tumor-to-background ratio). These reagents, therefore, have the
      potential for use in clinical imaging studies of cancer in the field of nuclear
      medicine.

PMID- 11585868
TI  - Multivalent single-chain antibodies for radioimaging of tumors.

PMID- 11585869
TI  - Conjugation with (111)In-DTPA-poly(ethylene glycol) improves imaging of anti-EGF
      receptor antibody C225.
AB  - Significant liver uptake often limits the clinical application of radiolabeled
      antibodies in radioimmunodetection. The purpose of this study was to evaluate the
      gamma-imaging properties of an antiepidermal growth factor receptor (EGFR)
      antibody, C225, conjugated with heterofunctional poly(ethylene glycol) (PEG) with
      1 terminus of the polymer attached to a radiometal chelator,
      diethylenetriaminepentaacetic acid (DTPA). METHODS: Two preparations of PEG
      modified C225, one with 20% and the other with 60% amine substitution, were
      labeled with (111)In. The conjugates, (111)In-DTPA-PEG-C225, were injected
      intravenously into nude mice with EGFR-positive A431 tumors. For comparison, C225
      directly labeled with (111)In was also injected. In a competitive study, mice
      with A431 tumors were pretreated intravenously with 100-fold excess of native
      C225, followed by an injection of (111)In-DTPA-PEG-C225 30 min or 20 h later. In
      addition, (111)In-DTPA-PEG-C225 was injected into mice with EGFR-positive MDA-MB
      468 tumors and EGFR-negative MDA-MB-435 tumors. Images were acquired at 5 min and
      at 2, 6, 24, and 48 h after injection of the radiotracers. Regions of interest
      (ROIs) were drawn on the computer images around the whole body, liver, muscle,
      and tumor. The counts per pixel in the tumor and normal tissues were calculated.
      At 48 h, the mice were killed and dissected. Blood, liver, muscle, and tumor
      samples were removed and the radioactivity of each sample was measured. RESULTS:
      In A431 tumor xenografts, the tumor uptake of C225 modified with PEG was not
      significantly different than the uptake of unmodified (111)In-DTPA-C225. Uptake
      in the liver, however, was reduced by 38%-45%, and the reduction increased with
      increasing degree of PEG substitution. Tumors of A431 and MDA-MB-468 xenografts
      were clearly visualized with (111)In-DTPA-PEG-C225, whereas tumors of the MDA-MB
      435 xenograft, which expresses low levels of EGFR, were not as readily visible.
      The tumor-to-blood ratios of (111)In-DTPA-PEG-C225 in A431 and MDA-MB-468
      xenografts were about 3 fold higher than in MDA-MB-435 xenografts. Blocking EGFR
      by pretreatment with native C225 significantly reduced the uptake of (111)In-DTPA
      PEG-C225 in the liver. The tumor-to-blood ratios in mice with A431 tumors were
      decreased 2.5-2.7 fold after pretreatment with a large excess of C225. Similar
      results were obtained with MDA-MB-468 tumor xenografts. In contrast, the tumor-to
      blood ratios in mice with MDA-MB-435 tumor xenografts were not significantly
      different in C225-pretreated mice than in nonpretreated mice. CONCLUSION: These
      findings indicate that (111)In-DTPA-PEG-C225 selectively localized to the tumors
      expressing high levels of EGFR. PEG-modification of C225 significantly reduced
      its liver uptake, resulting in improved visualization of EGFR-positive tumors.
      Using PEG as a linker between the monoclonal antibody and metal chelator is a
      useful strategy to optimize the imaging characteristics of antibody-based
      scintigraphic agents.

PMID- 11585870
TI  - Comparative cellular catabolism and retention of astatine-, bismuth-, and lead
      radiolabeled internalizing monoclonal antibody.
AB  - Monoclonal antibodies (mAbs) labeled with alpha-emitting radionuclides such as
      (211)At, (212)Bi, (213)Bi, and (212)Pb (which decays by beta-emission to its
      alpha-emitting daughter, (212)Bi) are being evaluated for their potential
      applications for cancer therapy. The fate of these radionuclides after cells are
      targeted with mAbs is important in terms of dosimetry and tumor detection.
      METHODS: In this study, we attached various radionuclides that result in alpha
      emissions to T101, a rapidly internalizing anti-CD5 mAb. We then evaluated the
      catabolism and cellular retention and compared them with those of (125)I- and
      (111)In-labeled T101. T101 was labeled with (211)At, (125)I, (205,6)Bi, (111)In,
      and (203)Pb. CD5 antigen-positive cells, peripheral blood mononuclear cells
      (PBMNC), and MOLT-4 leukemia cells were used. The labeled T101 was incubated with
      the cells for 1 h at 4 degrees C for surface labeling. Unbound activity was
      removed and 1 mL medium added. The cells were then incubated at 37 degrees C for
      0, 1, 2, 4, 8, and 24 h. The activity on the cell surface that internalized and
      the activity on the cell surface remaining in the supernatant were determined.
      The protein in the supernatant was further precipitated by methanol for
      determining protein-bound and non-protein-bound radioactivity. Sites of internal
      cellular localization of radioactivity were determined by Percoll gradient
      centrifugation. RESULTS: All radiolabeled antibodies bound to the cells were
      internalized rapidly. After internalization, (205,6)Bi, (203)Pb, and (111)In
      radiolabels were retained in the cell, with little decrease of cell-associated
      radioactivity. However, (211)At and (125)I were released from cells rapidly
      ((211)At < (125)I) and most of the radioactivity in the supernatant was in a non
      protein-bound form. Intracellular distribution of radioactivity revealed a
      transit of the radiolabel from the cell surface to the lysosome. The catabolism
      patterns of MOLT-4 cells and PBMNC were similar. CONCLUSION: (211)At catabolism
      and release from cells were somewhat similar to that of (125)I, whereas (205,6)Bi
      and (203)Pb showed prolonged cell retention similar to that of (111)In. These
      catabolism differences may be important in the selection of alpha-radionuclides
      for radioimmunotherapy.

PMID- 11585871
TI  - High-dose treatment with (186)Re-HEDP or (153)Sm-EDTMP combined with amifostine
      in a rabbit model.
AB  - The aim of this experimental study was to investigate the myeloprotective
      potential of amifostine in rabbits receiving high-dose treatment with either
      (153)Sm-ethylenediaminetetramethylene phosphonate (EDTMP) or (186)Re
      hydroxyethylidene diphosphonate (HEDP) and to check for drug interactions
      impairing the skeletal uptake of these radiopharmaceuticals by amifostine.
      METHODS: To a total of 24 rabbits, we administered 1,000 MBq of either (153)Sm
      EDTMP (n = 12) or (186)Re-HEDP (n = 12). Six animals of each group received 500
      mg amifostine intravenously 10-15 min before injection of the
      radiopharmaceutical, whereas the other 6 animals served as controls. Up to 8 wk
      after treatment, blood samples were collected every 3-5 d to measure platelet and
      leukocyte counts. Furthermore, whole-body images were acquired at 3 min, 3 h, and
      24 h after injection of the radiopharmaceutical to quantify the skeletal uptake.
      RESULTS: For (186)Re-HEDP, the mean decrease in platelets was significantly less
      in the amifostine group (35.5% +/- 2.4%) than in the control group (61.3% +/-
      5.4%, P < 0.001). Similar results were found for (153)Sm-EDTMP (36.5% +/- 8.3%
      vs. 52.3% +/- 14.0%, P < 0.05). No significant differences in leukocyte counts
      were found for (186)Re-HEDP (75.3% +/- 12.3% in the amifostine group and 72.5% +/
      4.1% in the control group, P > 0.05), whereas rabbits treated with (153)Sm-EDTMP
      plus amifostine showed a significantly greater decrease in leukocytes (69.2% +/-
      10.8%) than did the control group (56.6% +/- 4.0%, P < 0.05). Bone uptake in
      percentage of initial total whole-body activity was significantly decreased in
      animals treated with amifostine compared with the control groups for both (186)Re
      HEDP (15.8% +/- 3.1% vs. 30.9% +/- 1.9%, P < 0.001) and (153)Sm-EDTMP (31.7% +/-
      8.9% vs. 44.0% +/- 6.5%, P < 0.05). CONCLUSION: For amifostine, we found a highly
      significant cytoprotective effect on platelets but no leukoprotective effect. The
      latter probably relies on the intrinsic myelotoxicity of high-dose amifostine,
      which seemed to potentiate the leukodepression of the radiopharmaceuticals. The
      lower bone uptake in amifostine-treated animals may be caused by the chemical
      structure of amifostine, which is a potentially complex-forming compound that may
      be able to displace bisphosphonates from the rhenium- and samarium-bisphosphonate
      complexes, resulting in altered biodistribution patterns.

PMID- 11585872
TI  - FDG uptake and glucose transporter subtype expressions in experimental tumor and
      inflammation models.
AB  - Although FDG uptake is closely related to the expression of the glucose
      transporter (GLUT) in malignant tumors, such a relationship has not been fully
      investigated in inflammatory lesions. The aim of our study was to determine the
      expression of GLUT subtypes in experimental inflammatory lesions and to compare
      the results with those in malignant tumors in relation to FDG accumulation.
      METHODS: Rats were inoculated with a suspension of Staphylococcus aureus or
      allogenic hepatoma cells (KDH-8) into the left calf muscle. Five days after S.
      aureus inoculation (n = 9) and 14 d after KDH-8 inoculation (n = 11), [(14)C]FDG
      was injected intravenously and its accumulation in the infectious and tumor
      tissues was determined as the percentage activity of the injected dose per gram
      of tissue (%ID/g). The expression of glucose transporters (GLUT-1 to GLUT-5) was
      investigated by immunostaining the infectious tissues (n = 6) and the tumor
      tissues (n = 6). Immunohistochemical grading was assessed semiquantitatively by 5
      observers. RESULTS: The [(14)C]FDG uptake was significantly higher in the tumor
      lesion than in the inflammatory lesion (2.04 +/- 0.38 %ID/g vs. 0.72 +/- 0.15
      %ID/g; P < 0.0001). The tumor and inflammatory tissues highly expressed GLUT-1
      and GLUT-3. The GLUT-1 expression level was significantly higher in the tumor
      tissue than in the inflammatory tissue (P < 0.05). CONCLUSION: The results based
      on our models showed a high FDG uptake and high GLUT-1 expression level not only
      in the tumor lesion but also in the inflammatory lesion. The higher GLUT-1
      expression level in the tumor lesion may partially explain the higher FDG
      accumulation in the tumor than in the inflammatory lesion.

PMID- 11585873
TI  - Quantification of serotonin transporters in nonhuman primates using [(123)I]ADAM
      and SPECT.
AB  - We reported recently a highly selective radioligand, 2-([2
      ([dimethylamino]methyl)phenyl]thio)-5-[(123)I]iodophenylamine (ADAM), for SPECT
      imaging of serotonin transporters (SERT). In this article we describe the kinetic
      modeling of [(123)I]ADAM and its ability to quantitatively and reproducibly
      measure the concentrations of SERT in the nonhuman primate brain. We also
      investigate simplified models of tracer behavior that do not require invasive
      arterial blood sampling. METHODS: Three female baboons each underwent 3
      [(123)I]ADAM SPECT studies. The studies consisted of a dynamic sequence of
      seventy-two 5-min scans after injection of 330 +/- 50 MBq (mean +/- SD)
      [(123)I]ADAM. Rapid arterial blood samples were obtained and corrected for the
      presence of labeled metabolites. Dynamic imaging and metabolite-corrected plasma
      data were analyzed using graphic analysis to give the distribution volumes (DVs)
      of different brain regions. DV ratios (DVRs) of target to cerebellum were derived
      and compared against a kinetic reference tissue model and simple target-to
      background ratio. RESULTS: Averaged over all 9 scans, the mean DV in the midbrain
      was 4.86 +/- 1.06 mL/mL and the mean DV in the cerebellum was 2.25 +/- 0.48
      mL/mL. The mean test-retest repeatability of the midbrain DV was 14.5%. The
      reference tissue model gave a mean midbrain DVR of 2.01 +/- 0.17 and correlated
      strongly with the DVR calculated from the full kinetic model (correlation
      coefficient [R(2)] = 0.94; P < 0.001), but with much improved repeatability (test
      retest, 5.4%; intersubject variability, 5.2%). Similarly, the simple ratio method
      gave strong correlations with the full kinetic model (R(2) = 0.89; P < 0.001) and
      a test-retest of 7.6%. CONCLUSION: Accurate, repeatable quantification of SERT in
      the nonhuman primate brain is possible using kinetic modeling of dynamic
      [(123)I]ADAM SPECT scans. Simplified models, which do not require arterial blood
      sampling, gave accurate results that correlated strongly with the full kinetic
      model. The test-retest reliability of the simplified reference region models was
      excellent. Quantification of SERT is possible using full kinetic modeling and
      also with simpler reference region methods.

PMID- 11585874
TI  - Registration of emission and transmission whole-body scintillation-camera images.
AB  - In this work, a method for registration of whole-body (WB) scintillation-camera
      images is presented. The primary motive for the development is to perform
      activity quantification using the conjugate view method on an image basis.
      Accurate image registration is required for sequential anterior and posterior
      scans, for serial emission images for analysis of the biokinetics, and for
      transmission and emission images for a pixel-based attenuation correction.
      METHODS: Registration is performed by maximization of the mutual information. The
      spatial transformation has been tailored for the registration of WB images and is
      composed of global and local transformations, including rigid, projective, and
      curved transformations. A coarse registration is first performed using cross
      correlation and direct pixel scaling. Optimization is then performed in a
      sequence, beginning with the 2 legs independently, followed by the upper body and
      head. Evaluation is performed for clinical images of an (131)I-labeled monoclonal
      antibody and for Monte Carlo-simulated images. An anthropomorphic WB computer
      phantom, which has been especially modified to match the patient position during
      WB scanning, is used for the simulations. RESULTS: For simulated images,
      registration errors are within 1 pixel (<3.6 mm) for a sufficient image count
      level. Separate evaluation of the influence of noise shows that the errors
      increase below a total image count of approximately 10(5) (signal-to-noise ratio,
      approximately 4). For clinical evaluations, the deviations between point markers
      are 9 +/- 5 mm. CONCLUSION: An automatic registration method for WB images has
      been developed, which is applicable to emission-emission and transmission
      emission registration. This method has been applied in more than 50 clinical
      studies and has shown to be robust and reliable.

PMID- 11585875
TI  - Accuracy of ventricular volume and ejection fraction measured by gated myocardial
      SPECT: comparison of 4 software programs.
AB  - Gated myocardial perfusion SPECT has been used to calculate ejection fraction
      (EF) and end-diastolic volume (EDV) and has correlated well with conventional
      methods. However, the comparative accuracy of and correlations across various
      types of gated SPECT software are not well understood. METHODS: Mathematic
      phantoms of cylindric-hemispheric hybrid models, ranging in volume from 34 to 266
      mL, were generated. The clinical cases consisted of 30 patients who participated
      in a radionuclide angiography and gated blood-pool (GBP) study in addition to
      undergoing (99m)Tc-sestamibi gated SPECT. Four kinds of software, Quantitative
      Gated SPECT (QGS), the Emory Cardiac Toolbox (ECT), 4D-MSPECT, and Perfusion and
      Functional Analysis for Gated SPECT (pFAST) were used to compute EF and EDV, and
      the results were analyzed by multiple comparisons tests. Patients were classified
      into 4 groups (i.e., no defect, small defect, large defect, and small heart) so
      that factors affecting variation could be analyzed. RESULTS: In mathematic models
      > or = 74 mL, volume error was within +/-15%, whereas for a small volume (34 mL),
      QGS and 4D-MSPECT underestimated the volume and pFAST overestimated it. The
      respective intra- and interobserver reproducibility of the results was good for
      QGS (r = 0.99 and 1.00), ECT (r = 0.98 and 0.98), and 4D-MSPECT (r = 0.98 and
      0.98) and fair for pFAST (r = 0.88 and 0.85). The correlation coefficient for EF
      between gated SPECT and the GBP study was 0.82, 0.78, 0.69, and 0.84 for QGS,
      ECT, 4D-MSPECT, and pFAST, respectively. The correlation coefficient for EDV
      between gated SPECT and the GBP study was 0.88, 0.89, 0.85, and 0.90,
      respectively. Although good correlation was observed among the 4 software
      packages, QGS, ECT, and 4D-MSPECT overestimated EF in patients with small hearts,
      and pFAST overestimated the true volume in patients with large perfusion defects.
      Correlation coefficients among the 4 kinds of software were 0.80-0.95 for EF and
      0.89-0.98 for EDV. CONCLUSION: All 4 software programs showed good correlation
      between EF or EDV and the GBP study. Good correlation was observed also between
      each pair of quantification methods. However, because each method has unique
      characteristics that depend on its specific algorithm and thus behaves
      differently in the various patient subgroups, the methods should not be used
      interchangeably.

PMID- 11585876
TI  - Phantom studies for estimation of defect size on cardiac (18)F SPECT and PET:
      implications for myocardial viability assessment.
AB  - SPECT with (18)F-FDG has emerged as an alternative to dedicated PET for the
      assessment of myocardial viability. However, whether FDG SPECT can reliably
      quantify the extent of viable and scarred myocardium is uncertain. The aim of
      this study was to investigate whether SPECT with an (18)F-labeled agent would
      provide information on defect size similar to that provided by dedicated PET.
      METHODS: Imaging was performed using an elliptic cylinder chest phantom with
      simulated bone, lung, mediastinum, liver, and heart. (18)F was administered into
      the myocardium, mediastinum, right and left ventricular cavities, and liver.
      Plastic inserts (n = 11) ranging in size from 2% to 60% of the myocardium were
      used to simulate transmural myocardial infarctions. The chest phantom was imaged
      with a dedicated PET camera and with a double-head SPECT camera equipped with
      ultra-high-energy collimators. Both SPECT and PET data were analyzed using a
      semiquantitative polar map approach. Defects were quantified using various cutoff
      thresholds ranging from 30% to 80% of peak activity and were expressed as a
      percentage of the left ventricular myocardium. Defect size as measured by SPECT
      or PET was compared with true defect size. RESULTS: The measured SPECT defect
      size was highly variable depending on the cutoff used, whereas PET defect size
      was relatively constant over the range of cutoffs tested. The mean absolute
      difference between measured and true defect sizes was minimal at a cutoff of 50%
      of peak activity for both SPECT (3.3% +/- 3.3%) and PET (2.7% +/- 2.5%). For this
      threshold, both SPECT and PET measurements showed an excellent correlation with
      true defect size (r = 0.98 for SPECT and 0.99 for PET). The correlation between
      SPECT and PET measurements was also excellent (r = 0.99; P < 0.01). CONCLUSION:
      If an appropriate threshold is used to define a defect, SPECT with an (18)F
      labeled agent can accurately measure defect size similarly to the manner of PET.

PMID- 11585877
TI  - Intrahepatic (90)Y-microspheres for hepatocellular carcinoma.

PMID- 11585878
TI  - Dr. Gary J. Becker young investigator award: comparison of small-diameter type 1
      collagen stent-grafts and PTFE stent-grafts in a canine model--work in progress.
AB  - PURPOSE: To report an in-progress experiment in a canine model in which two types
      of small-diameter stent-grafts-one constructed of polytetrafluoroethylene (PTFE)
      and the other of a new, type 1 collagen material-were compared regarding vessel
      patency, intimal hyperplasia formation, and tissue reaction. MATERIALS AND
      METHODS: Six mongrel dogs weighing 30-35 kg were used. Stent-grafts of 4-mm
      diameter and 20-mm length were constructed with use of balloon-expandable
      stainless-steel stents wrapped with either PTFE or a new type 1 collagen graft.
      Stent-grafts were placed in deep femoral arteries bilaterally (PTFE on one side,
      collagen on the other). Animals were followed for 2 weeks (n = 2), 6 weeks (n =
      2), or 12 weeks (n = 2). Percent stenosis based on angiographic findings as well
      as thickness and area of neointimal hyperplasia were compared at each time point
      and compared with use of the Student t test. RESULTS: All devices were patent in
      the immediate postimplantation period. Five of six collagen stent-grafts and five
      of six PTFE implants were patent at follow-up. In-stent stenosis was undetectable
      angiographically in all five patent collagen stent-grafts. All five patent PTFE
      stent-grafts showed demonstrable in-stent stenosis (10%-60%), indicating a trend
      toward improved patency in collagen stent-grafts versus PTFE stent-grafts (P =
      .07). Neointimal hyperplasia was absent at 2 weeks in the collagen stent-grafts.
      Neointimal thickness increased to a maximum of 360 microm at 12 weeks in the
      collagen stent-grafts. For PTFE stent-grafts, neointimal hyperplasia was present
      in all samples and reached a maximum of 770 microm at 12 weeks (P = .03).
      CONCLUSIONS: Even in small-diameter vessels, type 1 collagen stent-grafts
      demonstrate excellent patency rates and favorable histologic findings. The type 1
      collagen stent-graft technology merits further developmental efforts in
      preclinical models.

PMID- 11585879
TI  - Image-guided radiofrequency tumor ablation: challenges and opportunities--part
      II.

PMID- 11585880
TI  - The Legs For Life Screening for Peripheral Vascular Disease: results of a
      prospective study designed to improve patient compliance with physician
      recommendations.
AB  - PURPOSE: To determine how compliance with recommendations made by physicians
      during the 2000 Legs For Life National Screening for Peripheral Vascular Disease
      (PVD) and Leg Pain is affected through the use of (i) simple and concise patient
      information and recommendation cards and (ii) a "targeted" postscreening follow
      up plan. MATERIALS AND METHODS: Patients were initially screened for PVD by
      completion of the Legs For Life Risk Factor Assessment form and determination of
      bilateral ankle/brachial indexes (ABIs). Each patient then met with an
      interventional radiologist or vascular surgeon. Patients with normal ABIs (>1.0
      bilaterally) or mildly abnormal ABIs (<1.0 but >0.90) were classified as having
      no risk and low risk, respectively. Patients with ABIs of 0.70-0.89 were
      classified as having moderate risk for PVD and patients with ABIs <0.69 were
      classified as having high risk for PVD. Physicians reviewed the Risk Factor
      Assessment form with each patient and made specific lifestyle improvement
      recommendations. For the year 2000 screening, patients classified at moderate and
      high risk for PVD received special instructions and a card containing clearly
      printed information on the purpose of the Legs For Life screening, their level of
      risk for PVD, specific recommendations for follow-up, and phone numbers to call
      to help arrange for that follow-up. Two weeks after the screening, a second copy
      of this card was mailed to each moderate- and high-risk assessed patient. Four
      months later, each of these patients was contacted by telephone to determine if
      they had pursued additional care or testing. RESULTS: A total of 185 patients
      were screened, 42 (23%) of whom were determined to be at moderate or high risk
      for PVD. Four months after the screening, 39 (93%) of these patients were
      available for follow-up. Twenty (51%) patients had received no further medical
      advice or treatment. Nineteen (49%) patients had pursued further medical care
      which included physician consultation (n = 19; 100%), noninvasive Doppler
      evaluation (n = 10; 26%), diagnostic arteriography (n = 2; 5%), initiation of
      pharmacologic therapy for claudication (n = 1; 3%), percutaneous intervention (n
      = 1; 3%), or vascular surgery (n = 1; 3%). Seventeen of 39 patients (44%)
      reported that claudication-type leg pain was still a concern and/or lifestyle
      limiting problem. CONCLUSION: Patients can be provided with problem-focused
      information and succinct physician recommendations at and soon after a screening
      for PVD, which can contribute to enhanced patient compliance. However, a host of
      personal, social, health, and physician-related issues still prevent a large
      percentage of patients from achieving relief of PVD-associated leg pain.

PMID- 11585881
TI  - Thrombosed hemodialysis grafts: lyse and wait with tissue plasminogen activator
      or urokinase compared to mechanical thrombolysis with the Arrow-Trerotola
      Percutaneous Thrombolytic Device.
AB  - PURPOSE: To determine if the lyse and wait (L&W) technique with a 4-mg dose of
      alteplase (tissue plasminogen activator; tPA) is a safe and effective method of
      declotting dialysis grafts as compared to use of the Arrow-Trerotola Percutaneous
      Thrombectomy Device (PTD) or the L&W technique with use of urokinase (UK).
      MATERIALS AND METHODS: Forty patients were randomized prospectively to undergo
      L&W declotting with use of 4 mg of tPA or mechanical thrombolysis with the PTD.
      The time interval to restored graft flow, total procedure time, hemostasis time,
      and anatomic success, clinical success, complications, and patency rates were
      analyzed. These were compared with historic results in 20 patients treated with
      the L&W technique with use of 250,000 U UK. RESULTS: The immediate anatomic
      success rate was 95% in the tPA L&W and PTD groups. The mean in-room lysis time
      with restored flow was 10 minutes for L&W with tPA and 19 minutes for PTD (P =
      .002). The mean in-room procedure time was 39 minutes for L&W and 45 minutes for
      PTD (P = NS). Mean hemostasis time with use of manual compression was 44 minutes
      for L&W with tPA and 23 minutes for PTD (P = .057). The historic group of 20
      patients who underwent L&W with UK had a 95% anatomic success rate, a mean of 14
      minutes of lysis time, a mean of 34 minutes of procedure time, and a mean of 26
      minutes of time to hemostasis. No bleeding complications occurred in the PTD
      group. Seven episodes of bleeding occurred in six patients given tPA; four were
      delayed 60-90 minutes after the procedure, one necessitated hospitalization, and
      two required additional therapies. Four of the 20 patients undergoing L&W with UK
      had minor puncture site bleeding during the procedure. The 3-month primary
      patency rates were 65%, 65%, and 60% for L&W with tPA, PTD, and L&W with UK,
      respectively (P = NS). CONCLUSION: The 4-mg dose of tPA is effective but results
      in more bleeding complications and longer hemostasis times than mechanical
      thrombolysis with use of the PTD. Unlike in our experience with UK, bleeding
      complications with tPA were both major and delayed.

PMID- 11585882
TI  - Endovenous laser treatment of the incompetent greater saphenous vein.
AB  - PURPOSE: To assess the safety and preliminary efficacy of endovenous laser
      treatment (EVLT), a novel percutaneous technique for occlusion of the incompetent
      greater saphenous vein (GSV). MATERIALS AND METHODS: Ninety GSVs in 84 patients
      with reflux at the saphenofemoral junction (SFJ) into the GSV were treated
      endovenously with pulses of laser energy and evaluated in a prospective,
      nonrandomized, consecutive enrollment multicenter study. Patients were evaluated
      at 1 week and at 1, 3, 6, and 9 months to determine efficacy and complications.
      RESULTS: Eighty-seven of 90 GSVs (97%) were closed 1 week after initial treatment
      with endovenous laser. The remaining three GSVs were closed after repeat
      treatment. Eighty-nine of 90 GSVs (99%) remained closed for as long as 9 months
      according to serial duplex ultrasonography. Sonographic evaluation demonstrated
      73% reduction in GSV diameter at 6 months (61 patients) and 81% reduction in GSV
      diameter at 9 months (26 patients) after EVLT. One patient developed a transient
      localized skin paresthesia. There have been no other minor or major
      complications. CONCLUSIONS: EVLT of the incompetent GSV appears to be an
      extremely safe technique that yields impressive short-term results. Long-term
      follow-up is awaited.

PMID- 11585883
TI  - Peripherally inserted central catheters with distal versus proximal valves:
      prospective randomized trial.
AB  - PURPOSE: To evaluate whether peripherally inserted central catheters (PICCs) with
      a proximal valve have any advantage compared to those with a distal valve in
      regard to the incidence of occlusion, infection, or malfunction. MATERIALS AND
      METHODS: One hundred patients (mean age, 46 y) were randomized to receive either
      a distal-valved Bard Groshong catheter (n = 48) or a proximal-valved Catheter
      Innovations Pressure Activated Safety Valve catheter (n = 52). All catheters were
      4-F, single-lumen PICCs. Catheters were placed under fluoroscopic (n = 82) or
      sonographic (n = 18) guidance. Most (91%) were placed for the administration of
      antibiotics. The placement procedure, maintenance, and weekly follow-up were the
      same for both catheters. RESULTS: Percutaneous placement with the catheter tip in
      the central veins was successful in all patients. Mean dwell time was 36 days.
      There were 12 (25%) occlusive or infectious complications in the distal valve
      catheter group and six (11.5%) in the proximal valve group (P = .08). There were
      25 fractures in 17 distal valve catheters (35.4%) and three (5.8%) proximal valve
      catheter fractures (P < .01). CONCLUSION: There was a marked difference in
      durability between the valved catheters, in favor of the catheter with a proximal
      valve. There was also a trend for fewer occlusive and infectious complications
      with the proximal valve catheter.

PMID- 11585884
TI  - Effect of MR angiography on the diagnosis and treatment of patients with
      suspected renovascular disease.
AB  - PURPOSE: Although the diagnostic accuracy of renal magnetic resonance (MR)
      angiography is established, its effect on referring physicians is unknown. The
      authors prospectively measured the effect of MR angiography results on referring
      physicians' diagnosis and treatment (plans) of patients with suspected
      renovascular disease. MATERIALS AND METHODS: Referring physicians prospectively
      completed questionnaires before and after MR angiography was performed during
      evaluation of their patients with suspected renovascular disease. The
      questionnaires asked them to estimate the probability (0%-100%) of their most
      likely diagnosis before and after receiving the imaging information. They were
      also asked for their anticipated and final treatment plans. The authors
      calculated the mean gain in diagnostic percentage confidence and the proportion
      of patients with changed initial diagnoses or anticipated management. A paired t
      test was used to assess significance of the gains in diagnostic percentage
      confidence. RESULTS: Physicians prospectively completed pre- and post-MR
      angiography questionnaires for 30 patients. MR angiography improved mean
      diagnostic certainty by 35% (P < .0001). MR angiography changed physicians'
      initial diagnoses in 12 patients (40%). Anticipated treatment plans were changed
      in 20 patients (67%). Invasive procedures were avoided in eight patients (27%).
      CONCLUSION: MR angiography has a substantial effect on the diagnostic and
      therapeutic decision-making of physicians managing patients with suspected
      renovascular disease.

PMID- 11585885
TI  - Comparison of in vitro effectiveness of mechanical thrombectomy devices.
AB  - PURPOSE: To determine the in vitro efficacy of clot removal of the following
      hydrodynamic thrombectomy devices: the AngioJet (AJ), Hydrolyser (HL), Oasis
      (OS), and Amplatz Thrombectomy Device (ATD). All devices have 6-F catheters.
      MATERIALS AND METHODS: Thrombectomy of 5-day-old porcine clots (n = 68; 8.5 g)
      was performed with the AJ without a guide wire [AJ(gw0)], with a coaxial 0.016
      inch guide wire [AJ(gw.016)], and with a 0.035-inch guide wire [AJ(gw.035)]), and
      with the HL, OS, and ATD in an artery flow model (pulsed flow: 700 L/min)
      simulating the superficial femoral artery (7-mm inner tube diameter). The
      effluent was passed through a three-step filter system (10-1,000 microm; pressure
      drop: 35 mm Hg). RESULTS: Mean thrombectomy time ranged from 49 seconds (AJ(gw0))
      to 88 seconds (OS; P < .001). The fluid balance with use of the AJ(gw.035) was
      0.89, whereas the mean ratio of applied saline solution to aspirated fluid for
      the other devices was not isovolumetric (AJ(gw0), 0.8; AJ(gw.016), 0.78; HL,
      0.73; OS, 0.62; P < .05). Remaining thrombus ranged in size from 8.2 mg (AJ(gw0))
      to 27.3 mg (AJ(gw.035); P = .079). Hydrodynamic devices (0.6% [OS] to 0.98%
      [AJ(gw.016)]) caused low amounts of added emboli greater 10 microm, 100 microm,
      and 1,000 microm. The ATD (5.19%) caused the most extensive embolization (P <
      .001). CONCLUSIONS: The tested mechanical thrombectomy devices have the power for
      sufficient thrombectomy in vitro; however, they showed moderate differences in
      performance. In contrast to hydrodynamic devices, the ATD fragmentation device
      showed a higher peripheral embolization rate of particles larger than 1,000
      microm; adjunctive in vivo treatment would probably be required.

PMID- 11585886
TI  - Dynamic intrahepatic flow and cellular alterations during radiofrequency ablation
      of liver tissue in mice.
AB  - PURPOSE: The purpose of this study was to identify microvascular and other
      associated changes that occur in the liver during focal heating with monopolar
      radiofrequency (RF). MATERIALS AND METHODS: Intravital video microscopy was
      performed on exteriorized transilluminated livers of 15 live mice during RF
      induced heating of liver parenchyma. Microvascular flow parameters, flow
      reversibility, microbubble formation, phagocytic activity, and endothelial
      permeability were recorded throughout a range of tip temperatures (40 degrees C
      95 degrees C). RESULTS: During RF application, five discrete zones extended
      outward from the electrode surface: (i) tissue coagulation, (ii) cellular
      edema/necrosis, (iii) sinusoidal stasis, (iv) parenchymal shunting, and (v)
      normal liver tissue. Reversal of stasis in sinusoids and small (<25 microm)
      vessels occurred at tip temperatures below 50 degrees C. This zone of stasis
      corresponded to the hyperemic zone on histologic analysis. Although alterations
      in permeability and phagocytic activity were first identified at 43 degrees C,
      tip temperatures higher than 55 degrees C always produced local endothelial
      leakiness to carbon microparticles at the periphery and always inhibited
      phagocytic activity. At tip temperatures higher than 95 degrees C, microbubble
      formation occurred with bubbles ultimately tracking through necrotic tissue into
      patent sinusoids. Larger peripheral vessels (>30 microm) limited extension of
      coagulation. CONCLUSION: Although coagulation occurs at tip temperatures higher
      than 50 degrees C, RF heating induced reversible microvascular stasis at
      temperatures lower than 50 degrees C. Increased sinusoidal endothelial
      permeability occurs at near-coagulative temperatures. Therefore, targeted
      endovascular microparticle delivery through this leaky endothelium may provide an
      additional and complimentary adjunct for RF ablation therapy.

PMID- 11585887
TI  - Therapeutic elastase inhibition by alpha-1-antitrypsin gene transfer limits
      neointima formation in normal rabbits.
AB  - PURPOSE: Alpha-1-antitrypsin (AAT) is the major circulating elastase inhibitor.
      Deficiency of elastase inhibition leads to emphysema and vascular abnormalities
      including accelerated neointima. Because recent evidence suggests that tissue AAT
      levels determine inhibitory function, the authors hypothesize that local tissue
      based expression of AAT limits elastase activity sufficiently to guide arterial
      response to injury. MATERIALS AND METHODS: Rabbit common femoral arteries were
      injured by mechanical overdilation and treated with buffer, viral control, or an
      adenovirus expressing AAT (Ad/AAT). After 3 and 28 days, intima-to-media (I/M)
      ratios were evaluated. Additionally, early changes in elastase inhibition
      potential (3 d), extracellular elastin and collagen content (3 d), and local
      macrophage and neutrophil infiltration (7 d) were determined. RESULTS: Ad/AAT
      significantly decreased neointima formation after mechanical dilation injury
      after 28 days: buffer controls exhibited mean I/M ratios of 0.76 +/- 0.06,
      whereas viral controls reached 0.77 +/- 0.09; in contrast, Ad/AAT reduced I/M
      ratios to 0.44 +/- 0.06. Both early elastin and collagen content were preserved
      in the Ad/AAT group relative to controls. The Ad/AAT group also reversed the
      local inflammation that characterized viral controls. CONCLUSIONS: This strategy
      demonstrates that local increases in elastase inhibition potential promote a
      neointima-resistant small-caliber artery, which may offer new promise in
      management of patients undergoing angioplasty.

PMID- 11585888
TI  - Recent trends in central venous catheter placement: a comparison of
      interventional radiology with other specialties.
AB  - The authors determined changing trends and growth in tunneled and nontunneled
      central venous catheter placement procedures. With use of Medicare billing data
      for tunneled and nontunneled catheter placement, a comparison was made among
      interventional radiology (IR), surgery, anesthesia, and internal medicine. There
      has been substantial growth in the placement of central venous catheters.
      Currently, a minority of these procedures are performed in IR departments.
      However, there has been significant growth in the radiologic placement of both
      types of catheters.

PMID- 11585889
TI  - Intraarterial chemotherapy of liver metastases: implantation of a microcatheter
      port system with use of modified fixed catheter tip technique.
AB  - A new method was developed to implant a microcatheter-port system for repeat
      intraarterial chemotherapy of liver metastases. The microcatheter-port system was
      successfully implanted in all 20 patients reported in this study, and the only
      complications were one early occlusion of the hepatic artery and one dislocation
      of the implanted catheter.

PMID- 11585890
TI  - Ultrasound guidance in accessing the afferent limb of a modified Roux-en-Y
      choledochojejunostomy for percutaneous dilation of biliary strictures.
AB  - Percutaneous retrograde biliary dilation via the afferent limb of a modified Roux
      en-Y choledochojejunostomy is used in the management of chronic biliary
      strictures. Access to the afferent loop may be challenging in the absence of
      surgically placed radiopaque markers. Ultrasound (US) guidance was used to access
      the loop in 10 patients with subcutaneous afferent loops and three patients with
      subfascial afferent loops. Successful puncture was made in all 10 patients with
      subcutaneous loops and in one patient with a subfascial loop. Initial
      fluoroscopically guided attempts failed in five loops, which were then
      successfully accessed with use of US guidance. US is useful in accessing
      subcutaneous afferent loops.

PMID- 11585891
TI  - Type III heart block with peripheral use of the Angiojet thrombectomy system.
AB  - The authors describe the occurrence of type III heart block in a patient
      undergoing a transjugular intrahepatic portosystemic shunt recanalization with
      use of the AngioJet thrombectomy system.

PMID- 11585892
TI  - Percutaneous closure of a subclavian artery injury after inadvertent
      catheterization.
AB  - Life-threatening complications of subclavian central venous access are rare.
      Herein a case of inadvertent subclavian artery catheterization and subsequent
      percutaneous arterial repair with use of the Prostar XL suture-mediated closure
      device and temporary balloon tamponade is reported. This approach obviated a
      complex surgical intervention that would have required medial clavicle resection.

PMID- 11585893
TI  - Spontaneous extraperitoneal hemorrhage with hemodynamic collapse in patients
      undergoing anticoagulation: management with selective arterial embolization.
AB  - The authors report their experience with management of unstable spontaneous
      extraperitoneal hemorrhage (SEH) with selective transcatheter embolization. Five
      consecutive patients underwent angiographic evaluation for SEH complicated by
      hemodynamic collapse while undergoing anticoagulation therapy. Bleeding occurred
      via one or two lumbar arteries in psoas hematomas. Two abdominal wall hematomas
      were supplied by the inferior epigastric artery, with additional supply via the
      deep circumflex iliac artery in one. Microcoil embolization successfully
      controlled extravasation in all patients, with stabilization of hemodynamic
      parameters. Four of the five patients survived the immediate postprocedural
      interval. Selective transcatheter embolization may be a viable life-saving option
      in SEH-associated hemodynamic collapse.

PMID- 11585894
TI  - Re: Appraising decision and cost-effective analyses.

PMID- 11585895
TI  - Re: Use of an Amplatz Goose Neck Snare as a target for collateral neck vein
      dialysis catheter placement.

PMID- 11585896
TI  - Structural and evolutionary relationships among protein tyrosine phosphatase
      domains.

PMID- 11585897
TI  - Zap-70-independent Ca(2+) mobilization and Erk activation in Jurkat T cells in
      response to T-cell antigen receptor ligation.
AB  - The tyrosine kinase ZAP-70 has been implicated as a critical intermediary between
      T-cell antigen receptor (TCR) stimulation and Erk activation on the basis of the
      ability of dominant negative ZAP-70 to inhibit TCR-stimulated Erk activation, and
      the reported inability of anti-CD3 antibodies to activate Erk in ZAP-70-negative
      Jurkat cells. However, Erk is activated in T cells receiving a partial agonist
      signal, despite failing to activate ZAP-70. This discrepancy led us to reanalyze
      the ZAP-70-negative Jurkat T-cell line P116 for its ability to support Erk
      activation in response to TCR/CD3 stimulation. Erk was activated by CD3 cross
      linking in P116 cells. However, this response required a higher concentration of
      anti-CD3 antibody and was delayed and transient compared to that in Jurkat T
      cells. Activation of Raf-1 and MEK-1 was coincident with Erk activation.
      Remarkably, the time course of Ras activation was comparable in the two cell
      lines, despite proceeding in the absence of LAT tyrosine phosphorylation in the
      P116 cells. CD3 stimulation of P116 cells also induced tyrosine phosphorylation
      of phospholipase C-gamma1 (PLCgamma1) and increased the intracellular Ca(2+)
      concentration. Protein kinase C (PKC) inhibitors blocked CD3-stimulated Erk
      activation in P116 cells, while parental Jurkat cells were refractory to PKC
      inhibition. The physiologic relevance of these signaling events is further
      supported by the finding of PLCgamma1 tyrosine phosphorylation, Erk activation,
      and CD69 upregulation in P116 cells on stimulation with superantigen and antigen
      presenting cells. These results demonstrate the existence of two pathways leading
      to TCR-stimulated Erk activation in Jurkat T cells: a ZAP-70-independent pathway
      requiring PKC and a ZAP-70-dependent pathway that is PKC independent.

PMID- 11585898
TI  - Topoisomerase III acts upstream of Rad53p in the S-phase DNA damage checkpoint.
AB  - Deletion of the Saccharomyces cerevisiae TOP3 gene, encoding Top3p, leads to a
      slow-growth phenotype characterized by an accumulation of cells with a late S/G2
      content of DNA (S. Gangloff, J. P. McDonald, C. Bendixen, L. Arthur, and R.
      Rothstein, Mol. Cell. Biol. 14:8391-8398, 1994). We have investigated the
      function of TOP3 during cell cycle progression and the molecular basis for the
      cell cycle delay seen in top3Delta strains. We show that top3Delta mutants
      exhibit a RAD24-dependent delay in the G2 phase, suggesting a possible role for
      Top3p in the resolution of abnormal DNA structures or DNA damage arising during S
      phase. Consistent with this notion, top3Delta strains are sensitive to killing by
      a variety of DNA-damaging agents, including UV light and the alkylating agent
      methyl methanesulfonate, and are partially defective in the intra-S-phase
      checkpoint that slows the rate of S-phase progression following exposure to DNA
      damaging agents. This S-phase checkpoint defect is associated with a defect in
      phosphorylation of Rad53p, indicating that, in the absence of Top3p, the
      efficiency of sensing the existence of DNA damage or signaling to the Rad53
      kinase is impaired. Consistent with a role for Top3p specifically during S phase,
      top3Delta mutants are sensitive to the replication inhibitor hydroxyurea,
      expression of the TOP3 mRNA is activated in late G1 phase, and DNA damage
      checkpoints operating outside of S phase are unaffected by deletion of TOP3. All
      of these phenotypic consequences of loss of Top3p function are at least partially
      suppressed by deletion of SGS1, the yeast homologue of the human Bloom's and
      Werner's syndrome genes. These data implicate Top3p and, by inference, Sgs1p in
      an S-phase-specific role in the cellular response to DNA damage. A model
      proposing a role for these proteins in S phase is presented.

PMID- 11585899
TI  - Stress-specific activation and repression of heat shock factors 1 and 2.
AB  - Vertebrate cells express a family of heat shock transcription factors (HSF1 to
      HSF4) that coordinate the inducible regulation of heat shock genes in response to
      diverse signals. HSF1 is potent and activated rapidly though transiently by heat
      shock, whereas HSF2 is a less active transcriptional regulator but can retain its
      DNA binding properties for extended periods. Consequently, the differential
      activation of HSF1 and HSF2 by various stresses may be critical for cells to
      survive repeated and diverse stress challenges and to provide a mechanism for
      more precise regulation of heat shock gene expression. Here we show, using a
      novel DNA binding and detection assay, that HSF1 and HSF2 are coactivated to
      different levels in response to a range of conditions that cause cell stress.
      Above a low basal activity of both HSFs, heat shock preferentially activates
      HSF1, whereas the amino acid analogue azetidine or the proteasome inhibitor MG132
      coactivates both HSFs to different levels and hemin preferentially induces HSF2.
      Unexpectedly, we also found that heat shock has dramatic adverse effects on HSF2
      that lead to its reversible inactivation coincident with relocalization from the
      nucleus. The reversible inactivation of HSF2 is specific to heat shock and does
      not occur with other stressors or in cells expressing high levels of heat shock
      proteins. These results reveal that HSF2 activity is negatively regulated by heat
      and suggest a role for heat shock proteins in the positive regulation of HSF2.

PMID- 11585901
TI  - MEKK1 is essential for DT40 cell apoptosis in response to microtubule disruption.
AB  - Vinblastine and other microtubule-damaging agents, such as nocodazole and
      paclitaxel, cause cell cycle arrest at the G2/M transition and promote apoptosis
      in eukaryotic cells. The roles of these drugs in disrupting microtubule dynamics
      and causing cell cycle arrest are well characterized. However, the mechanisms by
      which these agents promote apoptosis are poorly understood. We disrupted the
      MEKK1 kinase domain in chicken bursal B-cell line DT40 by homologous
      recombination and have shown that it is essential for both vinblastine-mediated
      apoptosis and vinblastine-mediated c-Jun N-terminal protein kinase activation. In
      addition, our data indicate that vinblastine-mediated apoptosis in DT40 cells
      requires new protein synthesis but does not require G2/M arrest, suggesting that
      vinblastine-mediated cell cycle arrest and apoptosis are two independent
      processes.

PMID- 11585900
TI  - Arsenic trioxide is a potent inhibitor of the interaction of SMRT corepressor
      with Its transcription factor partners, including the PML-retinoic acid receptor
      alpha oncoprotein found in human acute promyelocytic leukemia.
AB  - The SMRT corepressor complex participates in transcriptional repression by a
      diverse array of vertebrate transcription factors. The ability to recruit SMRT
      appears to play a crucial role in leukemogenesis by the PML-retinoic acid
      receptor alpha (RARalpha) oncoprotein, an aberrant nuclear hormone receptor
      implicated in human acute promyelocytic leukemia (APL). Arsenite induces clinical
      remission of APL through a incompletely understood mechanism. We report here that
      arsenite is a potent inhibitor of the interaction of SMRT with its transcription
      factor partners, including PML-RARalpha. Arsenite operates, in part, through a
      mitogen-activated protein (MAP) kinase cascade culminating in phosphorylation of
      the SMRT protein, dissociation of SMRT from its nuclear receptor partners, and a
      relocalization of SMRT out of the nucleus into the cytoplasm of the cell.
      Conversely, inhibition of this MAP kinase cascade attenuates the effects of
      arsenite on APL cells. Our results implicate SMRT as an important biological
      target for the actions of arsenite in both normal and neoplastic cells.

PMID- 11585902
TI  - Repair of DNA strand breaks by the overlapping functions of lesion-specific and
      non-lesion-specific DNA 3' phosphatases.
AB  - In Saccharomyces cerevisiae, the apurinic/apyrimidinic (AP) endonucleases Apn1
      and Apn2 act as alternative pathways for the removal of various 3'-terminal
      blocking lesions from DNA strand breaks and in the repair of abasic sites, which
      both result from oxidative DNA damage. Here we demonstrate that Tpp1, a homologue
      of the 3' phosphatase domain of polynucleotide kinase, is a third member of this
      group of redundant 3' processing enzymes. Unlike Apn1 and Apn2, Tpp1 is specific
      for the removal of 3' phosphates at strand breaks and does not possess more
      general 3' phosphodiesterase, exonuclease, or AP endonuclease activities.
      Deletion of TPP1 in an apn1 apn2 mutant background dramatically increased the
      sensitivity of the double mutant to DNA damage caused by H2O2 and bleomycin but
      not to damage caused by methyl methanesulfonate. The triple mutant was also
      deficient in the repair of 3' phosphate lesions left by Tdp1-mediated cleavage of
      camptothecin-stabilized Top1-DNA covalent complexes. Finally, the tpp1 apn1 apn2
      triple mutation displayed synthetic lethality in combination with rad52, possibly
      implicating postreplication repair in the removal of unrepaired 3'-terminal
      lesions resulting from endogenous damage. Taken together, these results
      demonstrate a clear role for the lesion-specific enzyme, Tpp1, in the repair of a
      subset of DNA strand breaks.

PMID- 11585903
TI  - Physical and functional interactions of human DNA polymerase eta with PCNA.
AB  - Human DNA polymerase eta (hPoleta) functions in the error-free replication of UV
      damaged DNA, and mutations in hPoleta cause cancer-prone syndrome, the variant
      form of xeroderma pigmentosum. However, in spite of its key role in promoting
      replication through a variety of distorting DNA lesions, the manner by which
      hPoleta is targeted to the replication machinery stalled at a lesion site remains
      unknown. Here, we provide evidence for the physical interaction of hPoleta with
      proliferating cell nuclear antigen (PCNA) and show that mutations in the PCNA
      binding motif of hPoleta inactivate this interaction. PCNA, together with
      replication factor C and replication protein A, stimulates the DNA synthetic
      activity of hPoleta, and steady-state kinetic studies indicate that this
      stimulation accrues from an increase in the efficiency of nucleotide insertion
      resulting from a reduction in the apparent K(m) for the incoming nucleotide.

PMID- 11585904
TI  - Raf kinase inhibitor protein interacts with NF-kappaB-inducing kinase and TAK1
      and inhibits NF-kappaB activation.
AB  - The Raf kinase inhibitor protein (RKIP) acts as a negative regulator of the
      mitogen-activated protein (MAP) kinase (MAPK) cascade initiated by Raf-1. RKIP
      inhibits the phosphorylation of MAP/extracellular signal-regulated kinase 1
      (MEK1) by Raf-1 by disrupting the interaction between these two kinases. We show
      here that RKIP also antagonizes the signal transduction pathways that mediate the
      activation of the transcription factor nuclear factor kappa B (NF-kappaB) in
      response to stimulation with tumor necrosis factor alpha (TNF-alpha) or
      interleukin 1 beta. Modulation of RKIP expression levels affected NF-kappaB
      signaling independent of the MAPK pathway. Genetic epistasis analysis involving
      the ectopic expression of kinases acting in the NF-kappaB pathway indicated that
      RKIP acts upstream of the kinase complex that mediates the phosphorylation and
      inactivation of the inhibitor of NF-kappaB (IkappaB). In vitro kinase assays
      showed that RKIP antagonizes the activation of the IkappaB kinase (IKK) activity
      elicited by TNF-alpha. RKIP physically interacted with four kinases of the NF
      kappaB activation pathway, NF-kappaB-inducing kinase, transforming growth factor
      beta-activated kinase 1, IKKalpha, and IKKbeta. This mode of action bears
      striking similarities to the interactions of RKIP with Raf-1 and MEK1 in the MAPK
      pathway. Emerging data from diverse organisms suggest that RKIP and RKIP-related
      proteins represent a new and evolutionarily highly conserved family of protein
      kinase regulators. Since the MAPK and NF-kappaB pathways have physiologically
      distinct roles, the function of RKIP may be, in part, to coordinate the
      regulation of these pathways.

PMID- 11585905
TI  - Transforming growth factor beta1 (TGF-beta1) promotes endothelial cell survival
      during in vitro angiogenesis via an autocrine mechanism implicating TGF-alpha
      signaling.
AB  - Mouse capillary endothelial cells (1G11 cell line) embedded in type I collagen
      gels undergo in vitro angiogenesis. Cells rapidly reorganize and form capillary
      like structures when stimulated with serum. Transforming growth factor beta1 (TGF
      beta1) alone can substitute for serum and induce cell survival and tubular
      network formation. This TGF-beta1-mediated angiogenic activity depends on
      phosphatidylinositol 3-kinase (PI3K) and p42/p44 mitogen-activated protein kinase
      (MAPK) signaling. We showed that specific inhibitors of either pathway
      (wortmannin, LY-294002, and PD-98059) all suppressed TGF-beta1-induced
      angiogenesis mainly by compromising cell survival. We established that TGF-beta1
      stimulated the expression of TGF-alpha mRNA and protein, the tyrosine
      phosphorylation of a 170-kDa membrane protein representing the epidermal growth
      factor (EGF) receptor, and the delayed activation of PI3K/Akt and p42/p44 MAPK.
      Moreover, we showed that all these TGF-beta1-mediated signaling events, including
      tubular network formation, were suppressed by incubating TGF-beta1-stimulated
      endothelial cells with a soluble form of an EGF receptor (ErbB-1) or tyrphostin
      AG1478, a specific blocker of EGF receptor tyrosine kinase. Finally, addition of
      TGF-alpha alone poorly stimulated angiogenesis; however, by reducing cell death,
      it strongly potentiated the action of TGF-beta1. We therefore propose that TGF
      beta1 promotes angiogenesis at least in part via the autocrine secretion of TGF
      alpha, a cell survival growth factor, activating PI3K/Akt and p42/p44 MAPK.

PMID- 11585906
TI  - Ectopic expression of DREF induces DNA synthesis, apoptosis, and unusual
      morphogenesis in the Drosophila eye imaginal disc: possible interaction with
      Polycomb and trithorax group proteins.
AB  - The promoters of Drosophila genes encoding DNA replication-related proteins
      contain transcription regulatory element DRE (5'-TATCGATA) in addition to E2F
      recognition sites. A specific DRE-binding factor, DREF, positively regulates DRE
      containing genes. In addition, it has been reported that DREF can bind to a
      sequence in the hsp70 scs' chromatin boundary element that is also recognized by
      boundary element-associated factor, and thus DREF may participate in regulating
      insulator activity. To examine DREF function in vivo, we established transgenic
      flies in which ectopic expression of DREF was targeted to the eye imaginal discs.
      Adult flies expressing DREF exhibited a severe rough eye phenotype. Expression of
      DREF induced ectopic DNA synthesis in the cells behind the morphogenetic furrow,
      which are normally postmitotic, and abolished photoreceptor specifications of R1,
      R6, and R7. Furthermore, DREF expression caused apoptosis in the imaginal disc
      cells in the region where commitment to R1/R6 cells takes place, suggesting that
      failure of differentiation of R1/R6 photoreceptor cells might cause apoptosis.
      The DREF-induced rough eye phenotype was suppressed by a half-dose reduction of
      the E2F gene, one of the genes regulated by DREF, indicating that the DREF
      overexpression phenotype is useful to screen for modifiers of DREF activity.
      Among Polycomb/trithorax group genes, we found that a half-dose reduction of some
      of the trithorax group genes involved in determining chromatin structure or
      chromatin remodeling (brahma, moira, and osa) significantly suppressed and that
      reduction of Distal-less enhanced the DREF-induced rough eye phenotype. The
      results suggest a possibility that DREF activity might be regulated by protein
      complexes that play a role in modulating chromatin structure. Genetic crosses of
      transgenic flies expressing DREF to a collection of Drosophila deficiency stocks
      allowed us to identify several genomic regions, deletions of which caused
      enhancement or suppression of the DREF-induced rough eye phenotype. These
      deletions should be useful to identify novel targets of DREF and its positive or
      negative regulators.

PMID- 11585907
TI  - Targeted disruption of the transition protein 2 gene affects sperm chromatin
      structure and reduces fertility in mice.
AB  - During mammalian spermiogenesis, major restructuring of chromatin takes place. In
      the mouse, the histones are replaced by the transition proteins, TP1 and TP2,
      which are in turn replaced by the protamines, P1 and P2. To investigate the role
      of TP2, we generated mice with a targeted deletion of its gene, Tnp2.
      Spermatogenesis in Tnp2 null mice was almost normal, with testis weights and
      epididymal sperm counts being unaffected. The only abnormality in testicular
      histology was a slight increase of sperm retention in stage IX to XI tubules.
      Epididymal sperm from Tnp2-null mice showed an increase in abnormal tail, but not
      head, morphology. The mice were fertile but produced small litters. In step 12 to
      16 spermatid nuclei from Tnp2-null mice, there was normal displacement of
      histones, a compensatory translationally regulated increase in TP1 levels, and
      elevated levels of precursor and partially processed forms of P2. Electron
      microscopy revealed abnormal focal condensations of chromatin in step 11 to 13
      spermatids and progressive chromatin condensation in later spermatids, but
      condensation was still incomplete in epididymal sperm. Compared to that of the
      wild type, the sperm chromatin of these mutants was more accessible to
      intercalating dyes and more susceptible to acid denaturation, which is believed
      to indicate DNA strand breaks. We conclude that TP2 is not a critical factor for
      shaping of the sperm nucleus, histone displacement, initiation of chromatin
      condensation, binding of protamines to DNA, or fertility but that it is necessary
      for maintaining the normal processing of P2 and, consequently, the completion of
      chromatin condensation.

PMID- 11585908
TI  - The transcriptional repressor REST determines the cell-specific expression of the
      human MAPK8IP1 gene encoding IB1 (JIP-1).
AB  - Islet-brain 1 (IB1) is the human and rat homologue of JIP-1, a scaffold protein
      interacting with the c-Jun amino-terminal kinase (JNK). IB1 expression is mostly
      restricted to the endocrine pancreas and to the central nervous system. Herein,
      we explored the transcriptional mechanism responsible for this preferential islet
      and neuronal expression of IB1. A 731-bp fragment of the 5' regulatory region of
      the human MAPK8IP1 gene was isolated from a human BAC library and cloned upstream
      of a luciferase reporter gene. This construct drove high transcriptional activity
      in both insulin-secreting and neuron-like cells but not in unrelated cell lines.
      Sequence analysis of this promoter region revealed the presence of a neuron
      restrictive silencer element (NRSE) known to bind repressor zinc finger protein
      REST. This factor is not expressed in insulin-secreting and neuron-like cells. By
      mobility shift assay, we confirmed that REST binds to the NRSE present in the IB1
      promoter. Once transiently transfected in beta-cell lines, the expression vector
      encoding REST repressed IB1 transcriptional activity. The introduction of a
      mutated NRSE in the 5' regulating region of the IB1 gene abolished the repression
      activity driven by REST in insulin-secreting beta cells and relieved the low
      transcriptional activity of IB1 observed in unrelated cells. Moreover,
      transfection in non-beta and nonneuronal cell lines of an expression vector
      encoding REST lacking its transcriptional repression domain relieved IB1 promoter
      activity. Last, the REST-mediated repression of IB1 could be abolished by
      trichostatin A, indicating that deacetylase activity is required to allow REST
      repression. Taken together, these data establish a critical role for REST in the
      control of the tissue-specific expression of the human IB1 gene.

PMID- 11585909
TI  - Bid, a widely expressed proapoptotic protein of the Bcl-2 family, displays lipid
      transfer activity.
AB  - Bid is an abundant proapoptotic protein of the Bcl-2 family that is crucial for
      the induction of death receptor-mediated apoptosis in primary tissues such as
      liver. Bid action has been proposed to involve the relocation of its truncated
      form, tBid, to mitochondria to facilitate the release of apoptogenic cytochrome
      c. The mechanism of Bid relocation to mitochondria was unclear. We report here
      novel biochemical evidence indicating that Bid has lipid transfer activity
      between mitochondria and other intracellular membranes, thereby explaining its
      dynamic relocation to mitochondria. First, physiological concentrations of
      phospholipids such as phosphatidic acid and phosphatidylglycerol induced an
      accumulation of full-length Bid in mitochondria when incubated with light
      membranes enriched in endoplasmic reticulum. Secondly, native and recombinant
      Bid, as well as tBid, displayed lipid transfer activity under the same conditions
      and at the same nanomolar concentrations leading to mitochondrial relocation and
      release of cytochrome c. Thus, Bid is likely to be involved in the transport and
      recycling of mitochondrial phospholipids. We discuss how this new role of Bid may
      relate to its proapoptotic action.

PMID- 11585910
TI  - Molecular basis for telomere repeat divergence in budding yeast.
AB  - Telomerase is a ribonucleoprotein enzyme that adds repetitive sequences to the
      ends of linear chromosomes, thereby counteracting nucleotide loss due to
      incomplete replication. A short region of the telomerase RNA subunit serves as
      template for nucleotide addition onto the telomere 3' end. Although Saccharomyces
      cerevisiae contains only one telomerase RNA gene, telomere repeat sequences are
      degenerate in this organism. Based on a detailed analysis of the telomere
      sequences specified by wild-type and mutant RNA templates in vivo, we show that
      the divergence of telomere repeats is due to abortive reverse transcription in
      the 3' and 5' regions of the template and due to the alignment of telomeres in
      multiple registers within the RNA template. Through the interpretation of wild
      type telomere sequences, we identify nucleotides in the template that are not
      accessible for base pairing during substrate annealing. Rather, these positions
      become available as templates for reverse transcription only after alignment with
      adjacent nucleotides has occurred, indicating that a conformational change takes
      place upon substrate binding. We also infer that the central part of the template
      region is reverse transcribed processively. The inaccessibility of certain
      template positions for alignment and the processive polymerization of the central
      template portion may serve to reduce the possible repeat diversification and
      enhance the incorporation of binding sites for Rap1p, the telomere binding
      protein of budding yeast.

PMID- 11585911
TI  - Photic signaling by cryptochrome in the Drosophila circadian system.
AB  - Oscillations of the period (per) and timeless (tim) gene products are an integral
      part of the feedback loop that underlies circadian behavioral rhythms in
      Drosophila melanogaster. Resetting this loop in response to light requires the
      putative circadian photoreceptor cryptochrome (CRY). We dissected the early
      events in photic resetting by determining the mechanisms underlying the CRY
      response to light and by investigating the relationship between CRY and the light
      induced ubiquitination of the TIM protein. In response to light, CRY is degraded
      by the proteasome through a mechanism that requires electron transport. Various
      CRY mutant proteins are not degraded, and this suggests that an intramolecular
      conversion is required for this light response. Light-induced TIM ubiquitination
      precedes CRY degradation and is increased when electron transport is blocked.
      Thus, inhibition of electron transport may "lock" CRY in an active state by
      preventing signaling required either to degrade CRY or to convert it to an
      inactive form. High levels of CRY block TIM ubiquitination, suggesting a
      mechanism by which light-driven changes in CRY could control TIM ubiquitination.

PMID- 11585912
TI  - Transformation of chicken embryo fibroblasts by v-src uncouples beta1 integrin
      mediated outside-in but not inside-out signaling.
AB  - Adhesion of cells to extracellular matrix is mediated by integrin family
      receptors. The process of receptor-ligand binding is dependent on metabolic
      energy and is regulated by intracellular signals, termed inside-out signals. The
      strength of the initial alpha5beta1-mediated adhesion of v-src-transformed
      chicken embryo fibroblasts (v-srcCEF) was similar to that of normal CEF. A
      chemically cross-linked fibronectin substrate was able to restore cell spreading
      and the ability of v-srcCEF to assemble a fibronectin matrix. Over time, v-srcCEF
      showed decreased adhesion due to the reduction of alpha5beta1-fibronectin bonds
      consequent on the reduction of substrate-bound fibronectin due to the secretion
      of proteases by v-srcCEF. Excess synthesis of hyaluronic acid by v-srcCEF also
      reduced the alpha5beta1-fibronectin bonds and contributed to cell detachment at
      later times in culture. Thus, the adhesion defects were not due to a failure of
      alpha5beta1 function and adhesion of the v-srcCEF was alpha5beta1 dependent.
      Integrin-mediated adhesion also produces signals that affect cell proliferation
      and cell differentiation. An early consequence of these "outside-in" signals was
      the phosphorylation of FAK Y397 in direct proportion to the number of alpha5beta1
      fibronectin bonds formed. In contrast, v-srcCEF had an increased level of
      phosphorylation on five different tyrosines in FAK, and none of these
      phosphorylation levels were sensitive to the number of alpha5beta1-fibronectin
      bonds. In the absence of serum, CEF proliferation was sensitive to changes in
      alpha5beta1-mediated adhesion levels. Transformation by v-src increased the serum
      free proliferation rate and made it insensitive to alpha5beta1-mediated adhesion.
      Thus, the v-srcCEF were insensitive to the normal outside-in signals from
      alpha5beta1 integrin.

PMID- 11585913
TI  - Distinct RNP complexes of shuttling hnRNP proteins with pre-mRNA and mRNA:
      candidate intermediates in formation and export of mRNA.
AB  - Nascent pre-mRNAs associate with hnRNP proteins in hnRNP complexes, the natural
      substrates for mRNA processing. Several lines of evidence indicate that hnRNP
      complexes undergo substantial remodeling during mRNA formation and export. Here
      we report the isolation of three distinct types of pre-mRNP and mRNP complexes
      from HeLa cells associated with hnRNP A1, a shuttling hnRNP protein. Based on
      their RNA and protein compositions, these complexes are likely to represent
      distinct stages in the nucleocytoplasmic shuttling pathway of hnRNP A1 with its
      bound RNAs. In the cytoplasm, A1 is associated with its nuclear import receptor
      (transportin), the cytoplasmic poly(A)-binding protein, and mRNA. In the nucleus,
      A1 is found in two distinct types of complexes that are differently associated
      with nuclear structures. One class contains pre-mRNA and mRNA and is identical to
      previously described hnRNP complexes. The other class behaves as freely
      diffusible nuclear mRNPs (nmRNPs) at late nuclear stages of maturation and
      possibly associated with nuclear mRNA export. These nmRNPs differ from hnRNPs in
      that while they contain shuttling hnRNP proteins, the mRNA export factor REF, and
      mRNA, they do not contain nonshuttling hnRNP proteins or pre-mRNA. Importantly,
      nmRNPs also contain proteins not found in hnRNP complexes. These include the
      alternatively spliced isoforms D01 and D02 of the hnRNP D proteins, the E0
      isoform of the hnRNP E proteins, and LRP130, a previously reported protein with
      unknown function that appears to have a novel type of RNA-binding domain. The
      characteristics of these complexes indicate that they result from RNP remodeling
      associated with mRNA maturation and delineate specific changes in RNP protein
      composition during formation and transport of mRNA in vivo.

PMID- 11585914
TI  - Regulatory mechanisms controlling human hepatocyte nuclear factor 4alpha gene
      expression.
AB  - Hepatocyte nuclear factor 4alpha (HNF-4alpha) (nuclear receptor 2A1) is an
      essential regulator of hepatocyte differentiation and function. Genetic and
      molecular evidence suggests that the tissue-restricted expression of HNF-4alpha
      is regulated mainly at the transcriptional level. As a step toward understanding
      the molecular mechanism involved in the transcriptional regulation of the human
      HNF-4alpha gene, we cloned and analyzed a 12.1-kb fragment of its upstream
      region. Major DNase I-hypersensitive sites were found at the proximal promoter,
      the first intron, and the more-upstream region comprising kb -6.5, -8.0, and 
      8.8. By the use of reporter constructs, we found that the proximal-promoter
      region was sufficient to drive high levels of hepatocyte-specific transcription
      in transient-transfection assays. DNase I footprint analysis and electrophoretic
      mobility shift experiments revealed binding sites for HNF-1alpha and -beta, Sp-1,
      GATA-6, and HNF-6. High levels of HNF-4alpha promoter activity were dependent on
      the synergism between either HNF-1alpha and HNF-6 or HNF-1beta and GATA-6, which
      implies that at least two alternative mechanisms may activate HNF-4alpha gene
      transcription. Chromatin immunoprecipitation experiments with human hepatoma
      cells showed stable association of HNF-1alpha, HNF-6, Sp-1, and COUP-TFII with
      the promoter. The last factor acts as a repressor via binding to a newly
      identified direct repeat 1 (DR-1) sequence of the human promoter, which is absent
      in the mouse homologue. We present evidence that this sequence is a bona fide
      retinoic acid response element and that HNF-4alpha expression is upregulated in
      vivo upon retinoic acid signaling.

PMID- 11585915
TI  - Analysis of TAF90 mutants displaying allele-specific and broad defects in
      transcription.
AB  - Yeast TAF90p is a component of at least two transcription regulatory complexes,
      the general transcription factor TFIID and the Spt-Ada-Gcn5 histone
      acetyltransferase complex (SAGA). Broad transcription defects have been observed
      in mutants of other TAF(II)s shared by TFIID and SAGA but not in the only two
      TAF90 mutants isolated to date. Given that the numbers of mutants analyzed thus
      far are small, we isolated and characterized 11 temperature-sensitive mutants of
      TAF90 and analyzed their effects on transcription and integrity of the TFIID and
      SAGA complexes. We found that the mutants displayed a variety of allele-specific
      defects in their ability to support transcription and maintain the structure of
      the TFIID and SAGA complexes. Sequencing of the alleles revealed that all have
      mutations corresponding to the C terminus of the protein, with most clustering
      within the conserved WD40 repeats; thus, the C terminus of TAF90p is required for
      its incorporation into TFIID and function in SAGA. Significantly, inactivation of
      one allele, taf90-20, caused the dramatic reduction in the levels of total mRNA
      and most specific transcripts analyzed. Analysis of the structure and/or activity
      of both TAF90p-containing complexes revealed that this allele is the most
      disruptive of all. Our analysis defines the requirement for the WD40 repeats in
      preserving TFIID and SAGA function, demonstrates that the defects associated with
      distinct mutations in TAF90 vary considerably, and indicates that TAF90 can be
      classified as a gene required for the transcription of a large number of genes.

PMID- 11585916
TI  - Calmodulin binds to K-Ras, but not to H- or N-Ras, and modulates its downstream
      signaling.
AB  - Activation of Ras induces a variety of cellular responses depending on the
      specific effector activated and the intensity and amplitude of this activation.
      We have previously shown that calmodulin is an essential molecule in the down
      regulation of the Ras/Raf/MEK/extracellularly regulated kinase (ERK) pathway in
      cultured fibroblasts and that this is due at least in part to an inhibitory
      effect of calmodulin on Ras activation. Here we show that inhibition of
      calmodulin synergizes with diverse stimuli (epidermal growth factor, platelet
      derived growth factor, bombesin, or fetal bovine serum) to induce ERK activation.
      Moreover, even in the absence of any added stimuli, activation of Ras by
      calmodulin inhibition was observed. To identify the calmodulin-binding protein
      involved in this process, calmodulin affinity chromatography was performed. We
      show that Ras and Raf from cellular lysates were able to bind to calmodulin.
      Furthermore, Ras binding to calmodulin was favored in lysates with large amounts
      of GTP-bound Ras, and it was Raf independent. Interestingly, only one of the Ras
      isoforms, K-RasB, was able to bind to calmodulin. Furthermore, calmodulin
      inhibition preferentially activated K-Ras. Interaction between calmodulin and K
      RasB is direct and is inhibited by the calmodulin kinase II calmodulin-binding
      domain. Thus, GTP-bound K-RasB is a calmodulin-binding protein, and we suggest
      that this binding may be a key element in the modulation of Ras signaling.

PMID- 11585917
TI  - Restoration of nucleotide excision repair in a helicase-deficient XPD mutant from
      intragenic suppression by a trichothiodystrophy mutation.
AB  - The UV-sensitive V-H1 cell line has a T46I substitution mutation in the Walker A
      box in both alleles of XPD and lacks DNA helicase activity. We characterized
      three partial revertants that curiously display intermediate UV cytotoxicity (2-
      to 2.5-fold) but normal levels of UV-induced hprt mutations. In revertant RH1-26,
      the efficient removal of pyrimidine (6-4) pyrimidone photoproducts from both
      strands of hprt suggests that global-genomic nucleotide excision repair is
      normal, but the pattern of cyclobutane pyrimidine dimer removal suggests that
      transcription-coupled repair (TCR) is impaired. To explain the intermediate UV
      survival and lack of RNA synthesis recovery in RH1-26 after 10 J of UV/m(2), we
      propose a defect in repair-transcription coupling, i.e., the inability of the
      cells to resume or reinitiate transcription after the first TCR event within a
      transcript. All three revertants carry an R658H suppressor mutation, in one
      allele of revertants RH1-26 and RH1-53 and in both alleles of revertant RH1-3.
      Remarkably, the R658H mutation produces the clinical phenotype of
      trichothiodystrophy (TTD) in several patients who display intermediate UV
      sensitivity. The XPD(R658H) TTD protein, like XPD(T46I/R658H), is codominant when
      overexpressed in V-H1 cells and partially complements their UV sensitivity. Thus,
      the suppressing R658H substitution must restore helicase activity to the inactive
      XPD(T46I) protein. Based on current knowledge of helicase structure, the
      intragenic reversion mutation may partially compensate for the T46I mutation by
      perturbing the XPD structure in a way that counteracts the effect of this
      mutation. These findings have implications for understanding the differences
      between xeroderma pigmentosum and TTD and illustrate the value of suppressor
      genetics for studying helicase structure-function relationships.

PMID- 11585918
TI  - Absence of Dbp2p alters both nonsense-mediated mRNA decay and rRNA processing.
AB  - Dbp2p, a member of the large family of DEAD-box proteins and a yeast homolog of
      human p68, was shown to interact with Upf1p, an essential component of the
      nonsense-mediated mRNA decay pathway. Dbp2p:Upf1p interaction occurs within a
      large conserved region in the middle of Upf1p that is largely distinct from its
      Nmd2p and Sup35/45p interaction domains. Deletion of DBP2, or point mutations
      within its highly conserved DEAD-box motifs, increased the abundance of nonsense
      containing transcripts, leading us to conclude that Dbp2p also functions in the
      nonsense-mediated mRNA decay pathway. Dbp2p, like Upf1p, acts before or at
      decapping, is predominantly cytoplasmic, and associates with polyribosomes.
      Interestingly, Dbp2p also plays an important role in rRNA processing. In
      dbp2Delta cells, polyribosome profiles are deficient in free 60S subunits and the
      mature 25S rRNA is greatly reduced. The ribosome biogenesis phenotype, but not
      the mRNA decay function, of dbp2Delta cells can be complemented by the human p68
      gene. We propose a unifying model in which Dbp2p affects both nonsense-mediated
      mRNA decay and rRNA processing by altering rRNA structure, allowing specific
      processing events in one instance and facilitating dissociation of the
      translation termination complex in the other.

PMID- 11585919
TI  - claudin-18, a novel downstream target gene for the T/EBP/NKX2.1 homeodomain
      transcription factor, encodes lung- and stomach-specific isoforms through
      alternative splicing.
AB  - T/EBP/NKX2.1, a member of the NKX family of homeodomain-containing transcription
      factors, regulates the expression of a number of genes in lung and thyroid. Here
      we describe the isolation and characterization of a novel target gene, termed
      claudin-18, that is down-regulated in the lungs of T/ebp/Nkx2.1-null mouse
      embryos. The gene product exhibits an amino acid sequence similar to those of the
      claudin multigene family of proteins that constitute tight junction strands in
      epithelial cells. The gene was localized by fluorescence in situ hybridization to
      mouse chromosome 9 at region 9E3-F1 and to human chromosome 3 at region 3q21-23.
      The claudin-18 gene has two promoters, each with its own unique exon 1 that is
      spliced to common exons 2 through 5. Alternative usage of these promoters leads
      to production of lung and stomach-specific transcripts. The downstream lung
      specific promoter contains two T/EBP/NKX2.1 binding sites responsible for trans
      activation of the gene by T/EBP/NKX2.1 in lung cells. Only claudin-18 was down
      regulated in T/ebp/Nkx2.1-null embryo lungs among 11 claudin transcripts
      examined. Furthermore, the claudin-18 transcript has an alternative 12-bp
      insertion derived from the 5' end of intron 4, which produces a C-terminally
      truncated isoform in lung and stomach. Immunohistochemistry demonstrated complete
      membrane localization of claudin-18 with small focal dots in the lung and stomach
      epithelial cells. Immunogold electron microscopy analysis revealed that claudin
      18 is concentrated at the cell-cell borders of epithelial cells. These unique
      features suggest a potentially important role for claudin-18 in the structure and
      function of tight junctions in lung and stomach.

PMID- 11585920
TI  - Human T-cell lymphotropic virus type 1 Tax represses c-Myb-dependent
      transcription through activation of the NF-kappaB pathway and modulation of
      coactivator usage.
AB  - The proto-oncogene c-myb is essential for a controlled balance between cell
      growth and differentiation. Aberrant c-Myb activity has been reported for
      numerous human cancers, and enforced c-Myb transcription can transform cells of
      lymphoid origin by stimulating cellular proliferation and inhibiting apoptotic
      pathways. Here we demonstrate that activation of the NF-kappaB pathway by the
      HTLV-1 Tax protein leads to transcriptional inactivation of c-Myb. This
      conclusion was supported by the fact that Tax mutants unable to stimulate the NF
      kappaB pathway could not inhibit c-Myb transactivating functions. In addition,
      inhibition of Tax-mediated NF-kappaB activation by coexpression of IkappaBalpha
      restored c-Myb transcription, and Tax was unable to block c-Myb transcription in
      a NEMO knockout cell line. Importantly, physiological stimuli, such as signaling
      with the cellular cytokines tumor necrosis factor alpha, interleukin 1 beta (IL
      1beta), and lipopolysaccharide, also inhibited c-Myb transcription. These results
      uncover a new link between extracellular signaling and c-Myb-dependent
      transcription. The mechanism underlying NF-kappaB-mediated repression was
      identified as sequestration of the coactivators CBP/p300 by RelA. Interestingly,
      an amino-terminal deletion form of p300 lacking the C/H1 and KIX domains and
      unable to bind RelA retained the ability to stimulate c-Myb transcription and
      prevented NF-kappaB-mediated repression.

PMID- 11585921
TI  - SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin
      mediated protein degradation.
AB  - Notch receptors and their ligands play important roles in both normal animal
      development and pathogenesis. We show here that the F-box/WD40 repeat protein SEL
      10 negatively regulates Notch receptor activity by targeting the intracellular
      domain of Notch receptors for ubiquitin-mediated protein degradation. Blocking of
      endogenous SEL-10 activity was done by expression of a dominant-negative form
      containing only the WD40 repeats. In the case of Notch1, this block leads to an
      increase in Notch signaling stimulated by either an activated form of the Notch1
      receptor or Jagged1-induced signaling through Notch1. Expression of dominant
      negative SEL-10 leads to stabilization of the intracellular domain of Notch1. The
      Notch4 intracellular domain bound to SEL-10, but its activity was not increased
      as a result of dominant-negative SEL-10 expression. SEL-10 bound Notch4 via the
      WD40 repeats and bound preferentially to a phosphorylated form of Notch4 in
      cells. We mapped the region of Notch4 essential for SEL-10 binding to the C
      terminal region downstream of the ankyrin repeats. When this C-terminal fragment
      of Notch4 was expressed in cells, it was highly labile but could be stabilized by
      the expression of dominant-negative SEL-10. Ubiquitination of Notch1 and Notch4
      intracellular domains in vitro was dependent on SEL-10. Although SEL-10 interacts
      with the intracellular domains of both Notch1 and Notch4, these proteins respond
      differently to interference with SEL-10 function. Thus, SEL-10 functions to
      promote the ubiquitination of Notch proteins; however, the fates of these
      proteins may differ.

PMID- 11585922
TI  - Common regulation of growth arrest and differentiation of osteoblasts by helix
      loop-helix factors.
AB  - Cellular differentiation entails the coordination of cell cycle arrest and tissue
      specific gene expression. We investigated the involvement of basic helix-loop
      helix (bHLH) factors in differentiation of osteoblasts using the human
      osteoblastic cell line MG63. Serum starvation induced growth arrest at G1 phase,
      accompanied by expression of cyclin-dependent kinase inhibitor p21(WAF1/Cip1).
      Reporter assays with the p21 gene promoter demonstrated that the combination of
      E2A (E12 or E47) and coactivator CBP was responsible for p21 induction
      independent of p53. Twist inhibited E2A-CBP-dependent activation of the exogenous
      and endogenous p21 promoters. Ids similarly inhibited the exogenously transfected
      p21 promoter; however less antagonistic effect on the endogenous p21 promoter was
      observed. Twist was predominantly present in nuclei in MG63 cells growing in
      complete medium, while it localized mainly in the cytoplasm after serum
      starvation. The fibroblast growth factor receptor 3 gene (FGFR3), which generates
      signals leading to differentiation of osteoblasts, was found to be controlled by
      the same transcriptional regulation as the p21 gene. E2A and Twist influenced
      alkaline phosphatase expression, a consensus marker of osteoblast
      differentiation. Expression of E2A and FGFR3 was seen at the location of
      osteoblast differentiation in the calvaria of mouse embryos, implicating bHLH
      molecules in physiological osteoblast differentiation. These results demonstrate
      that a common regulatory system is involved in at least two distinct steps in
      osteoblastic differentiation. Our results also provide the molecular basis of
      Saethre-Chotzen syndrome, caused by mutations of the TWIST and FGFR3 genes.

PMID- 11585923
TI  - Downregulation of the Ras-mitogen-activated protein kinase pathway by the EphB2
      receptor tyrosine kinase is required for ephrin-induced neurite retraction.
AB  - Activation of the EphB2 receptor tyrosine kinase by clustered ephrin-B1 induces
      growth cone collapse and neurite retraction in differentiated NG108 neuronal
      cells. We have investigated the cytoplasmic signaling events associated with
      EphB2-induced cytoskeletal reorganization in these neuronal cells. We find that
      unlike other receptor tyrosine kinases, EphB2 induces a pronounced downregulation
      of GTP-bound Ras and consequently of the extracellular signal-regulated kinase
      (ERK) mitogen-activated protein kinase (MAPK) pathway. A similar inhibition of
      the Ras-MAPK pathway was observed on stimulation of endogenous EphB2 in COS-1
      cells. Inactivation of Ras, induced by ephrin B1 stimulation of NG108 neuronal
      cells, requires EphB2 tyrosine kinase activity and is blocked by a truncated form
      of p120-Ras GTPase-activating protein (p120-RasGAP), suggesting that EphB2
      signals through the SH2 domain protein p120-RasGAP to inhibit the Ras-MAPK
      pathway. Suppression of Ras activity appears functionally important, since
      expression of a constitutively active variant of Ras impaired the ability of
      EphB2 to induce neurite retraction. In addition, EphB2 attenuated the elevation
      in ERK activation induced by attachment of NG108 cells to fibronectin, indicating
      that the EphB2 receptor can modulate integrin signaling to the Ras GTPase. These
      results suggest that a primary function of EphB2, a member of the most populous
      family of receptor tyrosine kinases, is to inactivate the Ras-MAPK pathway in a
      fashion that contributes to cytoskeletal reorganization and adhesion responses in
      neuronal growth cones.

PMID- 11585924
TI  - Role of beta-dystrobrevin in nonmuscle dystrophin-associated protein complex-like
      complexes in kidney and liver.
AB  - beta-Dystrobrevin is a dystrophin-related and -associated protein that is highly
      expressed in brain, kidney, and liver. Recent studies with the kidneys of the
      mdx3Cv mouse, which lacks all dystrophin isoforms, suggest that beta
      dystrobrevin, and not the dystrophin isoforms, may be the key component in the
      assembly of complexes similar to the muscle dystrophin-associated protein
      complexes (DPC) in nonmuscle tissues. To understand the role of beta-dystrobrevin
      in the function of nonmuscle tissues, we generated beta-dystrobrevin-deficient
      (dtnb(-/-)) mice by gene targeting. dtnb(-/-) mice are healthy, fertile, and
      normal in appearance. No beta-dystrobrevin was detected in these mice by Western
      blotting or immunocytochemistry. In addition, the levels of several beta
      dystrobrevin-interacting proteins, namely Dp71 isoforms and the syntrophins, were
      greatly reduced from the basal membranes of kidney tubules and liver sinusoids
      and on Western blots of crude kidney and liver microsomes of beta-dystrobrevin
      deficient mice. However, no abnormality was detected in the ultrastructure of
      membranes of kidney and liver cells or in the renal function of these mice. beta
      Dystrobrevin may therefore be an anchor or scaffold for Dp71 and syntrophin
      isoforms, as well as other associating proteins at the basal membranes of kidney
      and liver, but is not necessary for the normal function of these mice.

PMID- 11585925
TI  - Inhibition of protein kinase B (PKB) and PKCzeta mediates keratin K10-induced
      cell cycle arrest.
AB  - The intermediate filament cytoskeleton is composed of keratins in all epithelial
      cells and imparts mechanical integrity to these cells. However, beyond this
      shared function, the functional significance of the carefully regulated tissue-
      and differentiation-specific expression of the large keratin family of
      cytoskeletal proteins remains unclear. We recently demonstrated that expression
      of keratin K10 or K16 may regulate the phosphorylation of the retinoblastoma
      protein (pRb), inhibiting (K10) or stimulating (K16) cell proliferation (J. M.
      Paramio, M. L. Casanova, C. Segrelles, S. Mittnacht, E. B. Lane, and J. L.
      Jorcano, Mol. Cell. Biol. 19:3086-3094, 1999). Here we show that keratin K10
      function as a negative modulator of cell cycle progression involves changes in
      the phosphoinositide 3-kinase (PI-3K) signal transduction pathway. Physical
      interaction of K10 with Akt (protein kinase B [PKB]) and atypical PKCzeta causes
      sequestration of these kinases within the cytoskeleton and inhibits their
      intracellular translocation. As a consequence, the expression of K10 impairs the
      activation of PKB and PKCzeta. We also demonstrate that this inhibition impedes
      pRb phosphorylation and reduces the expression of cyclins D1 and E. Functional
      and biochemical data also demonstrate that the interaction between K10 and these
      kinases involves the non-alpha-helical amino domain of K10 (NTerm). Together,
      these results suggest new and essential roles for the keratins as modulators of
      specific signal transduction pathways.

PMID- 11585926
TI  - The transcription factor GATA4 is activated by extracellular signal-regulated
      kinase 1- and 2-mediated phosphorylation of serine 105 in cardiomyocytes.
AB  - The zinc finger-containing transcription factor GATA4 has been implicated as a
      critical regulator of multiple cardiac-expressed genes as well as a regulator of
      inducible gene expression in response to hypertrophic stimulation. Here we
      demonstrate that GATA4 is itself regulated by the mitogen-activated protein
      kinase signaling cascade through direct phosphorylation. Site-directed
      mutagenesis and phospho-specific GATA4 antiserum revealed serine 105 as the
      primary site involved in agonist-induced phosphorylation of GATA4. Infection of
      cultured cardiomyocytes with an activated MEK1-expressing adenovirus induced
      robust phosphorylation of serine 105 in GATA4, while a dominant-negative MEK1
      expressing adenovirus blocked agonist-induced phosphorylation of serine 105,
      implicating extracellular signal-regulated kinase (ERK) as a GATA4 kinase.
      Indeed, bacterially purified ERK2 protein directly phosphorylated purified GATA4
      at serine 105 in vitro. Phosphorylation of serine 105 enhanced the
      transcriptional potency of GATA4, which was sensitive to U0126 (MEK1 inhibitor)
      but not SB202190 (p38 inhibitor). Phosphorylation of serine 105 also modestly
      enhanced the DNA binding activity of bacterially purified GATA4. Finally,
      induction of cardiomyocyte hypertrophy with an activated MEK1-expressing
      adenovirus was blocked with a dominant-negative GATA4-engrailed-expressing
      adenovirus. These results suggest a molecular pathway whereby MEK1-ERK1/2
      signaling regulates cardiomyocyte hypertrophic growth through the transcription
      factor GATA4 by direct phosphorylation of serine 105, which enhances DNA binding
      and transcriptional activation.

PMID- 11585927
TI  - Characterization of regulatory events associated with membrane targeting of p90
      ribosomal S6 kinase 1.
AB  - RSK is a serine/threonine kinase containing two distinct catalytic domains. Found
      at the terminus of the Ras/extracellular signal-regulated kinase (ERK)-mitogen
      activated protein kinase (MAPK) kinase cascade, mitogen-stimulated ribosomal S6
      kinase (RSK) activity requires multiple inputs. These inputs include
      phosphorylation of the C-terminal kinase domain activation loop by ERK1/2 and
      phosphorylation of the N-terminal kinase domain activation loop by
      phosphoinositide-dependent protein kinase-1 (PDK1). Previous work has shown that
      upon mitogen stimulation, RSK accumulates in the nucleus. Here we show that prior
      to nuclear translocation, epidermal growth factor-stimulated RSK1 transiently
      associates with the plasma membrane. Myristylation of wild-type RSK1 results in
      an activated enzyme in the absence of added growth factors. When RSK is truncated
      at the C terminus, the characterized ERK docking is removed and RSK
      phosphotransferase activity is completely abolished. When myristylated, however,
      this myristylated C-terminal truncated form (myrCTT) is activated at a level
      equivalent to myristylated wild-type (myrWT) RSK. Both myrWT RSK and myrCTT RSK
      can signal to the RSK substrate c-Fos in the absence of mitogen activation.
      Unlike myrWT RSK, myrCTT RSK is not further activated by serum. Only the
      myristylated RSK proteins are basally phosphorylated on avian RSK1 serine 381, a
      site critical for RSK activity. The myristylated and unmyristylated RSK
      constructs interact with PDK1 upon mitogen stimulation, and this interaction is
      insensitive to the MEK inhibitor UO126. Because a kinase-inactive CTT RSK can be
      constitutively activated by targeting to the membrane, we propose that ERK may
      have a dual role in early RSK activation events: preliminary phosphorylation of
      RSK and escorting RSK to a membrane-associated complex, where additional MEK/ERK
      independent activating inputs are encountered.

PMID- 11585928
TI  - Isolation of a murine homologue of the Drosophila neuralized gene, a gene
      required for axonemal integrity in spermatozoa and terminal maturation of the
      mammary gland.
AB  - The Drosophila neuralized gene shows genetic interactions with Notch, Enhancer of
      split, and other neurogenic genes and is thought to be involved in cell fate
      specification in the central nervous system and the mesoderm. In addition, a
      human homologue of the Drosophila neuralized gene has been described as a
      potential tumor suppressor gene in malignant astrocytomas. We have isolated a
      murine homologue of the Drosophila and human Neuralized genes and, in an effort
      to understand its physiological function, derived mice with a targeted deletion
      of this gene. Surprisingly, mice homozygous for the introduced mutation do not
      show aberrant cell fate specifications in the central nervous system or in the
      developing mesoderm. This is in contrast to mice with targeted deletions in other
      vertebrate homologues of neurogenic genes such as Notch, Delta, and Cbf-1. Male
      Neuralized null mice, however, are sterile due to a defect in axoneme
      organization in the spermatozoa that leads to highly compromised tail movement
      and sperm immotility. In addition, female Neuralized null animals are defective
      in the final stages of mammary gland maturation during pregnancy.

PMID- 11585929
TI  - Mechanism of poly(A) signal transduction to RNA polymerase II in vitro.
AB  - Termination of transcription by RNA polymerase II usually requires the presence
      of a functional poly(A) site. How the poly(A) site signals its presence to the
      polymerase is unknown. All models assume that the signal is generated after the
      poly(A) site has been extruded from the polymerase, but this has never been
      tested experimentally. It is also widely accepted that a "pause" element in the
      DNA stops the polymerase and that cleavage at the poly(A) site then signals
      termination. These ideas also have never been tested. The lack of any direct
      tests of the poly(A) signaling mechanism reflects a lack of success in
      reproducing the poly(A) signaling phenomenon in vitro. Here we describe a cell
      free transcription elongation assay that faithfully recapitulates poly(A)
      signaling in a crude nuclear extract. The assay requires the use of citrate, an
      inhibitor of RNA polymerase II carboxyl-terminal domain phosphorylation. Using
      this assay we show the following. (i) Wild-type but not mutant poly(A) signals
      instruct the polymerase to stop transcription on downstream DNA in a manner that
      parallels true transcription termination in vivo. (ii) Transcription stops
      without the need of downstream elements in the DNA. (iii) cis-antisense
      inhibition blocks signal transduction, indicating that the signal to stop
      transcription is generated following extrusion of the poly(A) site from the
      polymerase. (iv) Signaling can be uncoupled from processing, demonstrating that
      signaling does not require cleavage at the poly(A) site.

PMID- 11585930
TI  - The HOX homeodomain proteins block CBP histone acetyltransferase activity.
AB  - Despite the identification of PBC proteins as cofactors that provide DNA affinity
      and binding specificity for the HOX homeodomain proteins, HOX proteins do not
      demonstrate robust activity in transient-transcription assays and few authentic
      downstream targets have been identified for these putative transcription factors.
      During a search for additional cofactors, we established that each of the 14 HOX
      proteins tested, from 11 separate paralog groups, binds to CBP or p300. All six
      isolated homeodomain fragments tested bind to CBP, suggesting that the
      homeodomain is a common site of interaction. Surprisingly, CBP-p300 does not form
      DNA binding complexes with the HOX proteins but instead prevents their binding to
      DNA. The HOX proteins are not substrates for CBP histone acetyltransferase (HAT)
      but instead inhibit the activity of CBP in both in vitro and in vivo systems.
      These mutually inhibitory interactions are reflected by the inability of CBP to
      potentiate the low levels of gene activation induced by HOX proteins in a range
      of reporter assays. We propose two models for HOX protein function: (i) HOX
      proteins may function without CBP HAT to regulate transcription as cooperative
      DNA binding molecules with PBX, MEIS, or other cofactors, and (ii) the HOX
      proteins may inhibit CBP HAT activity and thus function as repressors of gene
      transcription.

PMID- 11585932
TI  - Risks in the community for persons with schizophrenia.

PMID- 11585934
TI  - Consumer & family information: HIV and AIDS.

PMID- 11585931
TI  - TAF(II)170 interacts with the concave surface of TATA-binding protein to inhibit
      its DNA binding activity.
AB  - The human RNA polymerase II transcription factor B-TFIID consists of TATA-binding
      protein (TBP) and the TBP-associated factor (TAF) TAF(II)170 and can rapidly
      redistribute over promoter DNA. Here we report the identification of human TBP
      binding regions in human TAF(II)170. We have defined the TBP interaction domain
      of TAF(II)170 within three amino-terminal regions: residues 2 to 137, 290 to 381,
      and 380 to 460. Each region contains a pair of Huntington-elongation-A subunit
      Tor repeats and exhibits species-specific interactions with TBP family members.
      Remarkably, the altered-specificity TBP mutant (TBP(AS)) containing a triple
      mutation in the concave surface is defective for binding the TAF(II)170 amino
      terminal region of residues 1 to 504. Furthermore, within this region the
      TAF(II)170 residues 290 to 381 can inhibit the interaction between Drosophila
      TAF(II)230 (residues 2 to 81) and TBP through competition for the concave surface
      of TBP. Biochemical analyses of TBP binding to the TATA box indicated that
      TAF(II)170 region 290-381 inhibits TBP-DNA complex formation. Importantly, the
      TBP(AS) mutant is less sensitive to TAF(II)170 inhibition. Collectively, our
      results support a mechanism in which TAF(II)170 induces high-mobility DNA binding
      by TBP through reversible interactions with its concave DNA binding surface.

PMID- 11585935
TI  - Datapoints: Spending for state mental health care.

PMID- 11585936
TI  - Law & psychiatry: Abuses of law and psychiatry in China.

PMID- 11585937
TI  - Economic grand rounds: Physician or payer: who determines length of stay?

PMID- 11585938
TI  - Managed care: Strengthening the consumer voice in managed care: II. Moving NCQA
      standards from rights to empowerment.

PMID- 11585939
TI  - Personal accounts: Strengths versus deficits, or musician versus schizophrenic.

PMID- 11585940
TI  - Housing attributes and serious mental illness: implications for research and
      practice.
AB  - OBJECTIVES: This paper critically reviews studies of the relationship between
      housing attributes and serious mental illness, highlights important gaps in the
      research, generates hypotheses to be tested, and suggests a research agenda.
      METHODS: Studies published between 1975 and March 2000 were identified through
      computerized searches, previous literature reviews, and consultation with mental
      health and housing researchers. Criteria for inclusion included the presentation
      of quantitative evidence, a systematic sample of known generalizability, and
      systematic analytic techniques. RESULTS AND CONCLUSIONS: The 32 studies that met
      these criteria relied on one or more of three conceptualizations of the role of
      housing: housing attributes or assessments as an outcome or dependent variable;
      housing attributes as inputs or independent variables in a model in which the
      outcome pertains to a nonhousing factor, such as a mental health outcome; or
      housing as both an input and an outcome. Three studies found no long-term effect
      of improved housing adequacy on housing satisfaction above and beyond case
      management. Three studies found better outcomes for settings that have fewer
      occupants. Another study suggested that persons who live in small-scale, good
      quality, noninstitutional environments are less likely to engage in disruptive
      behavior when a larger proportion of other tenants also have serious mental
      illness. The strongest finding from the literature on housing as an input and an
      outcome was that living in independent housing was associated with greater
      satisfaction with housing and neighborhood. Most of the studies had
      methodological weaknesses, and few addressed key hypotheses. There is a critical
      need for a coherent agenda built around key hypotheses and for a uniform set of
      measures of housing an input and an outcome.

PMID- 11585941
TI  - The case of Sam: multidisciplinary perspectives.

PMID- 11585949
TI  - Requirements for multidisciplinary teamwork in psychiatric rehabilitation.
AB  - Psychiatric rehabilitation by its very nature is multidisciplinary because of the
      many competencies required for its implementation. In promoting optimal levels of
      recovery from schizophrenia and other disabling mental disorders, teams must
      combine the expert contributions of professionals and paraprofessionals who can
      individualize a comprehensive array of evidence-based services with competency,
      consistency, continuity, coordination, collaboration, and fidelity. The authors
      describe the properties and functions of the multidisciplinary team and key
      attributes of effective teams. The importance of teams' involving clients, their
      relatives, and other supporters in setting personally relevant life goals is
      emphasized. The authors provide examples of the challenges posed by the need to
      individualize services and of the ways in which barriers to communication and
      coordination can be overcome. The roles of the various team members are
      described, including leadership roles and the unique role of the psychiatrist, in
      the context of newly emerging, evidence-based treatments for psychiatric
      rehabilitation.

PMID- 11585950
TI  - The role of correctional officers in multidisciplinary mental health care in
      prisons.
AB  - Prisons have become the homes of thousands of inmates who have mental disorders.
      The stress of incarceration can cause morbidity among these individuals,
      resulting in more severe symptoms and more disruptive behavior. Effective
      treatment for such inmates often involves services provided by a
      multidisciplinary treatment team that includes correctional officers.
      Correctional officers can assist in observations and interventions, and they play
      a unique role on specialized housing units. Successful collaboration between
      correctional officers and treatment teams requires a foundation of mutual
      respect, shared training, and ongoing communication and cooperation. With these
      elements in place, correctional officers can assist the treatment team and make
      important and constructive contributions to the assessment and management of
      offenders who have mental disorders.

PMID- 11585951
TI  - Collaboration among the education, mental health, and public health systems to
      promote youth mental health.
AB  - The authors discuss the growing movement in the United States to develop expanded
      school mental health programs. These programs represent partnerships between
      schools and community mental health agencies to expand the range of mental health
      services provided by schools. Such programs emphasize effective prevention,
      assessment, and intervention. The authors describe efforts that have been
      undertaken to improve the fragmented and incomplete nature of children's services
      and to proactively identify and address children's emotional and behavioral
      problems. They also discuss a strategy to improve youth mental health programs,
      which includes needs assessments and an analysis of existing programs in a
      community. They describe the augmenting roles played by the mental health and
      public health systems in expanding and improving school-based mental health
      services. The authors outline steps to minimize or avoid the turfism and negative
      attitudes that may arise among professionals from different disciplines when they
      collaborate to expand and improve school-based programs.

PMID- 11585952
TI  - A self-assessment program for multidisciplinary mental health teams.
AB  - OBJECTIVE: The authors describe a self-assessment training program for
      multidisciplinary mental health teams that was developed in a public
      multihospital system, the process of implementing the training at a state
      psychiatric hospital, and a measurement instrument, the Scale for Leadership
      Assessment and Team Evaluation (SLATE), which they have used for self-assessment
      of multidisciplinary teams and which is currently being studied. They assessed
      whether changes in team self-assessments could be seen after the training
      program. METHODS: A total of 102 mental health professionals from 12 inpatient
      units representing the disciplines of psychiatry, psychology, nursing, social
      work, and occupational and activity therapy completed the SLATE before and after
      participation in a training program that consisted primarily of team self
      assessment in the context of treatment planning sessions. The training program
      included structured feedback, didactics, consultation, and videotaping of
      sessions. Aggregate data were used to compare mean item scores for the SLATE
      overall and for its four subscales (team, psychiatrist, participation, and
      treatment plan) at baseline and after the training. RESULTS: Scores increased
      significantly for the overall SLATE and for all four subscales, indicating
      improved team functioning in the areas addressed. The increase in mean score was
      greatest for the subscale that assessed the leadership of the psychiatrist.
      CONCLUSIONS: Treatment planning sessions can be used successfully by
      multidisciplinary mental health teams to examine team functioning in various
      areas in a self-assessment model. Participation in a training program that
      included videotaping of sessions, consultation, and structured attention to team
      functioning was associated with improved ratings of team functioning.

PMID- 11585953
TI  - Risks for individuals with schizophrenia who are living in the community.
AB  - OBJECTIVE: This study examined the incidence and predictors of police contact,
      criminal charges, and victimization among noninstitutionalized individuals with
      schizophrenia living in the community. METHODS: A total of 172 individuals with
      schizophrenia or schizoaffective disorder were recruited from community-based
      programs in urban Los Angeles between 1989 and 1991 and were monitored for three
      years. At baseline, all participants were housed and did not have co-occurring
      substance use disorders. Face-to-face interviews were conducted every six months.
      RESULTS: Eighty-three individuals (48 percent) had contact with the police during
      the study period. A small percentage of the contacts involved aggressive behavior
      against property or persons. Being younger, having had more address changes at
      baseline, and having a history of arrest and assault were significant predictors
      of police contact. Thirty-seven individuals (22 percent) reported that charges
      had been filed against them. Poorer social functioning, more address changes,
      fewer days of taking medication at baseline, and a history of arrest and assault
      were significant predictors of criminal charges. Sixty-five participants (38
      percent of the sample) reported having been the victim of a crime during the
      three years, 91 percent of which was violent. Having more severe clinical
      symptoms and more substance use at baseline were significant predictors of
      victimization. CONCLUSIONS: Individuals in this sample were at least 14 times
      more likely to be victims of a violent crime than to be arrested for one. In
      general, the risk associated with being in the community was higher than the risk
      these individuals posed to the community

PMID- 11585954
TI  - Assessing predictive factors for extended hospitalization at acute psychiatric
      admission.
AB  - OBJECTIVE: This study examined whether information obtained early in the
      hospitalization process can be used to assess a patient's need for extended care.
      METHODS: A sample of 2,430 inpatients who were admitted to a state psychiatric
      facility during a one-year index period (January through December 1997) were
      randomly assigned to a primary sample or a replication sample. Data were
      collected on demographic characteristics and history of previous hospitalization.
      The Brief Psychiatric Rating Scale-Anchored Version (BPRS-A) was administered to
      patients within 48 hours of admission, and four new subscales derived from
      ratings of newly admitted patients were calculated. Univariate and multivariate
      analyses were conducted to identify factors associated with whether a patient was
      discharged to the community or transported to another hospital for extended care.
      RESULTS: A discriminant analysis of the data correctly identified 70 percent of
      the patients who were referred for continued hospitalization and 80 percent of
      the patients who were discharged to the community. The main correlates of the
      need for extended inpatient services were, in descending order, scores on the
      BPRS-A resistance subscale, the number of previous referrals for extended
      hospitalizations, and scores on the BPRS-A positive symptoms and psychological
      discomfort scales. CONCLUSIONS: BPRS-A subscale scores should be considered to be
      at least as good as more traditional measures in predicting length of
      hospitalization.

PMID- 11585955
TI  - Relationship between staffing ratios and effectiveness of inpatient psychiatric
      units.
AB  - OBJECTIVE: Most staffing models designed for adult psychiatric hospitals are
      based on the well-known relationship between high staff-patient ratios and high
      effectiveness of treatment units. Staffing ratios likely gain their predictive
      power by serving as a proxy measure for the amount of attention patients receive
      from staff. This study directly measured the amount of attention that patients
      received from staff to determine whether it could account for the variance in
      unit effectiveness predicted by staffing ratios and serve as a better predictor
      of unit effectiveness. METHODS: Data from 22 wards in state or Department of
      Veterans Affairs mental health institutions, which housed 673 short- and long
      stay patients, were analyzed. Only full-time direct care staff were included in
      the calculation of staff-patient ratios. The amount of attention provided to
      patients by staff was determined over seven days by a highly reliable
      observational assessment system. The two best social-action outcome measures over
      a six-month period were adjusted for confounding variables to provide
      residualized indexes of unit effectiveness. RESULTS: Staff-patient ratios
      significantly predicted unit effectiveness as indexed by residualized community
      tenure, accounting for 24 percent of the variance. However, staff-patient ratios
      did not significantly predict unit effectiveness as indexed by net gain in
      discharge rates. Taking into account the amount of staff attention received by
      patients significantly improved the prediction of community tenure by 36 percent
      and the net gain in discharge rates by 66 percent over staffing ratios alone. The
      amount of staff attention also accounted for the relationship between staffing
      ratios and community tenure. CONCLUSIONS: Staffing decisions should be made on
      the basis of more precise information about treatment requirements, not just
      staffing ratios.

PMID- 11585956
TI  - Gold award: Helping mentally ill people break the cycle of jail and homelessness.

PMID- 11585957
TI  - Gold award: A community-based program providing a successful alternative to acute
      psychiatric hospitalization.

PMID- 11585958
TI  - Significant achievement awards: Providing flexible, individualized services to
      the underserved--the Baltimore capitation project.

PMID- 11585959
TI  - Frontline reports: the August Aichhorn Center for Adolescent Residential Care.

PMID- 11585960
TI  - Frontline reports: Holocaust survivors' home.

PMID- 11585961
TI  - Frontline reports: New York State Office of Mental Health trauma initiative.

PMID- 11585962
TI  - A critique of the effectiveness of assertive community treatment.

PMID- 11585966
TI  - Internet addiction disorder among clients of a virtual clinic.

PMID- 11585967
TI  - Thymidine phosphorylase (TP) activation: convenience through innovation.

PMID- 11585968
TI  - The evolution of fluoropyrimidine therapy: from intravenous to oral.
AB  - Chemotherapy for advanced colorectal cancer is based on i.v. 5-fluorouracil (5
      FU). Numerous attempts have been made to increase the therapeutic benefit of 5-FU
      through schedule modification and biomodulation, but only modest improvements
      have been achieved. Capecitabine is an oral fluoropyrimidine that was developed
      in response to the clinical need for new therapeutic options offering improved
      efficacy, tolerability, and convenience for patients. Capecitabine was rationally
      designed to mimic continuous infusion 5-FU. It is rapidly and almost completely
      absorbed through the gastrointestinal wall and is converted to 5-FU via a three
      step enzymatic cascade. 5-FU is generated preferentially in tumor by exploiting
      the higher activity of thymidine phosphorylase in tumor tissue compared with
      normal tissue. Results of a randomized, phase II trial led to the selection of a
      regimen of capecitabine for further clinical development (1,250 mg/m(2) twice
      daily for 14 days followed by a 7-day rest period). Subsequently, two large,
      randomized, phase III trials were conducted to compare capecitabine with i.v.
      bolus 5-FU/leucovorin ([LV]; Mayo Clinic regimen) in patients with metastatic
      colorectal cancer. A prospective, integrated analysis of data from the studies
      showed that capecitabine offers superior activity and an improved safety profile
      compared with 5-FU/LV. This article summarizes these developments in the
      treatment of colorectal cancer and assesses the feasibility of replacing i.v. 5
      FU-based therapy with oral capecitabine. In addition, retrospective analyses
      assessing the impact of the dose modification scheme on the efficacy and
      tolerability of capecitabine are presented, and dose recommendations in special
      populations are reviewed.

PMID- 11585969
TI  - Answering patients' needs: oral alternatives to intravenous therapy.
AB  - Metastatic colorectal cancer has traditionally been treated with i.v. 5
      fluorouracil (5-FU), with or without leucovorin (LV). 5-FU is administered as
      either an i.v. bolus or a protracted infusion. Although schedules using the
      latter method offer efficacy benefits (objective response rate, time to disease
      progression), protracted infusion schedules are often associated with medical
      complications, inconvenience, high costs, and poor quality of life. Issues such
      as quality of life and convenience have influenced treatment decisions, but the
      availability of oral fluoropyrimidines represents a new development in this
      domain. Studies have confirmed that the majority of patients prefer oral to i.v.
      chemotherapy. Questionnaire-based studies have also demonstrated a preference for
      home-based rather than hospital-/clinic-based therapy. This preference was one of
      the driving forces behind the development of the oral fluoropyrimidines
      capecitabine (Xeloda) and uracil plus tegafur (UFT). Oral agents offer patients a
      more convenient treatment option that can be administered at home, providing
      patients with a greater sense of control over their therapy, while avoiding the
      medical complications and psychological distress associated with venous access.
      This article highlights some of the problems associated with i.v. therapy and
      reviews the available data on patient preference, including results of a recent,
      randomized, phase II study. It also provides a critical evaluation of the
      efficacy and safety profiles of the only two oral fluoropyrimidines approved for
      prescription, capecitabine and UFT/LV (UFT/LV not available in Germany and the
      U.S.), compared with those of two infused, 5-FU-based regimens. Finally, the
      results of an interactive debate exploring the opinions of approximately 400
      oncologists on the issues of oral versus i.v. therapy are presented.

PMID- 11585970
TI  - Optimizing the use of irinotecan in colorectal cancer.
AB  - The introduction of new agents with novel mechanisms of action has led to
      considerable changes in the management of colorectal cancer in recent years. One
      of these novel agents, irinotecan, has been shown to offer survival benefits in
      both the first- and second-line treatment of advanced/metastatic colorectal
      cancer. Irinotecan monotherapy improves survival compared with both best
      supportive care and infused 5-fluorouracil (5-FU) in patients with 5-FU
      pretreated disease, without impacting negatively on patients' quality of life. As
      a result, irinotecan monotherapy is now considered to be the standard treatment
      in this setting. Irinotecan in combination with 5-FU/leucovorin (LV) was
      subsequently evaluated as first-line therapy for metastatic colorectal cancer in
      two randomized, phase III studies. Both trials confirmed that irinotecan plus
      infused or bolus 5-FU/leucovorin LV provide a modest survival benefit without
      compromising patients' quality of life. Combined irinotecan/5-FU/LV represents a
      new standard in the first-line treatment of metastatic colorectal cancer. In an
      attempt to further improve efficacy and tolerability, recent studies have
      investigated irinotecan in combination with capecitabine as first-line treatment
      for colorectal cancer. The replacement of infused 5-FU with oral capecitabine
      provides a more convenient treatment option. A phase I study was conducted to
      establish the maximum tolerated dose, and demonstrated encouraging antitumor
      activity and a manageable safety profile with the combination. This article
      provides a brief overview of the pivotal clinical trial data for irinotecan and
      discusses how irinotecan-based therapy may be improved in the future. It also
      discusses potential optimization of irinotecan use through identification of
      patient subpopulations most likely to benefit from combination or sequential
      strategies, and the potential of new, oral agents such as capecitabine to replace
      i.v. 5-FU as a combination partner for irinotecan.

PMID- 11585971
TI  - Integrating oxaliplatin into the management of colorectal cancer.
AB  - Oxaliplatin, a third-generation platinum analogue, is a novel compound with
      proven anti-tumor activity in colorectal cancer that has demonstrated synergy
      with 5-fluorouracil (5-FU) in human tumor xenograft models. A series of phase II
      trials demonstrated that, as second-line therapy, oxaliplatin in combination with
      5-FU/leucovorin (LV) is active and can overcome clinical resistance to 5-FU.
      Subsequently, two large, randomized, phase III trials demonstrated that the
      addition of oxaliplatin to 5-FU/LV significantly improved response rates and time
      to disease progression in the first-line setting, but had no statistically
      significant impact on survival. Oxaliplatin in combination with 5-FU/LV
      represents an important treatment option for patients in whom 5-FU-based therapy
      has failed and as first-line therapy. Oxaliplatin has also been investigated in
      combination with the oral fluoropyrimidine, capecitabine. As an oral agent that
      exploits the high intratumoral activity of thymidine phosphorylase to generate 5
      FU preferentially within tumor tissue, capecitabine may improve the efficacy and
      tolerability of fluoropyrimidine/oxaliplatin combination therapy. A phase I dose
      escalation study has been performed in patients with advanced/metastatic solid
      tumors to establish the most appropriate regimen. The study indicated that the
      combination is feasible and has substantial antitumor activity in patients with
      colorectal cancer. This article provides an overview of the clinical trial data
      for oxaliplatin and discusses how oxaliplatin may best be used in the future.

PMID- 11585972
TI  - Improving chemoradiotherapy in rectal cancer.
AB  - The optimal management of rectal cancer remains a major challenge for
      oncologists. The treatment of stage II/III rectal cancer has historically been
      associated with a high risk of local recurrence and poor survival, which led to
      the development of adjuvant treatments in the hope of improving outcomes. The
      approach to adjuvant therapy for rectal cancer currently varies widely between
      Europe and the U.S. Postoperative adjuvant chemoradiation is the standard of care
      in the U.S. In contrast, in Europe, because there is a greater emphasis placed on
      preoperative imaging, meticulous surgical technique, and accurate pathologic
      reporting of the circumferential or radial margin, preoperative treatment
      (radiotherapy and chemoradiation) is used widely. The aims of preoperative
      radiotherapy and chemoradiation are to facilitate a curative resection (R0) and
      to increase the chance of performing sphincter-sparing procedures, and,
      therefore, to improve both survival and quality of life. This article reviews the
      clinical trials that led to these diverging standards of care. An interesting new
      approach in chemoradiation is the use of the oral fluoropyrimidine capecitabine
      as a combination partner for radiotherapy. Preclinical studies have demonstrated
      that the combination of capecitabine and radiotherapy has highly enhanced
      antitumor activity. This is most likely attributable to the upregulation of
      thymidine phosphorylase (the rate-limiting enzyme needed to convert capecitabine
      to 5-fluorouracil [5-FU]) in tumor cells following radiotherapy. A phase I study
      has consequently been performed to establish a feasible chemoradiotherapy
      combination. Capecitabine has the potential to replace bolus or continuous
      infusion 5-FU as the standard treatment for rectal cancer and offers a
      potentially enhanced therapeutic ratio. Oral chemotherapy has the additional
      advantage of simplifying chemoradiation and providing a treatment that is more
      appealing to patients.

PMID- 11585973
TI  - Vision of the future: capecitabine.
AB  - Capecitabine is a thymidine phosphorylase (TP)-activated oral fluoropyrimidine,
      rationally designed to generate 5-fluorouracil (5-FU) preferentially within
      tumors. This tumor selectivity is achieved through exploitation of the
      significantly higher activity of TP in tumor compared with healthy tissue. The
      high single-agent activity of capecitabine in breast and colorectal cancer
      suggests that capecitabine may have a role in the treatment of other tumor types
      that are sensitive to 5-FU, such as pancreatic cancer. Tumor types known to have
      a high level of TP activity, such as renal cancer, are especially attractive
      targets for capecitabine therapy. Capecitabine has potential as monotherapy in
      these tumor types, or as a combination partner for other cytotoxic agents with
      different mechanisms of action and little overlap of key toxicities. In
      particular, some cytotoxic drugs, such as the taxanes and cyclophosphamide, are
      known to upregulate TP activity in tumor tissue, offering the potential for
      synergistic action. The combination of capecitabine and docetaxel has
      demonstrated significant activity in women with anthracycline-pretreated breast
      cancer, and is the only cytotoxic combination to significantly increase survival
      compared with standard therapy in this setting. In addition, capecitabine as
      monotherapy or in combination with other cytotoxic agents has shown encouraging
      activity in pancreatic, ovarian, and renal cell cancers. This article discusses
      recent data from clinical trials investigating capecitabine in a range of tumor
      types, highlighting the potential future role of capecitabine as an alternative
      to traditional i.v. chemotherapy.

PMID- 11585974
TI  - Macronutrient, vitamin, and mineral intakes in the EPIC-Germany cohorts.
AB  - This article presents intakes of nutrients in the EPIC-Heidelberg and the EPIC
      Potsdam (European Investigation into Cancer and Nutrition) studies. Estimates are
      based on standardized 24-hour dietary recalls. Recalls from 1,013 men and 1,078
      women in Heidelberg and from 1,032 men and 898 women in Potsdam were included in
      the analysis. The estimated nutrient intake was based on the German Food Code and
      Nutrient Data Base version II.3. Analyses were carried out stratified by sex and
      weighted for the day of the week and age. Men in Potsdam reported significantly
      higher intakes of energy (mean Potsdam = 10,718 kJ, mean Heidelberg = 10,387 kJ)
      and higher intakes of vitamins and minerals as compared with men in Heidelberg.
      However, Heidelberg men consumed more alcohol, alpha-tocopherol, phosphorus,
      calcium, and magnesium. Potsdam women reported lower energy (mean Potsdam = 7,537
      kJ, mean Heidelberg = 7,855 kJ), alcohol, and cholesterol intakes as compared
      with Heidelberg women. Vitamin and mineral intakes were lower too, except for
      retinol and ascorbic acid. The intakes of energy and most nutrients observed in
      the Potsdam and Heidelberg study populations were within the range reported from
      other German studies. The observed differences between both study populations
      indicate different dietary patterns, increasing the exposure variation in the
      EPIC study.

PMID- 11585975
TI  - Antihypertensive treatment decreased serum leptin levels in severe preeclampsia
      during pregnancy.
AB  - BACKGROUND: Plasma leptin levels in preeclamptic patients have been reported to
      be similar compared to those of normotensive pregnant women. Nonetheless, no
      reports have dealt with the effect of antihypertensive treatment and leptin in
      preeclamptic patients. METHODS: The study involved three groups of a similar age,
      body mass index and weeks of gestation. The groups were 30 normal pregnant women
      and 23 pregnant women with severe preeclampsia (SPE). The SPE patients were not
      treated prior to admission and the treatment was a single dose of alpha
      methyldopa or hydralazine alone or in combination. The samples were taken at
      random in the afternoon (isotonic saline or pharmacological treatment) and 1 h
      before and after the treatment was given. Leptin serum levels were determined by
      a commercial sandwich ELISA assay. RESULTS: Leptin levels of the SPE group prior
      to the treatment were similar to the levels recorded for the normal pregnant
      women. However, after 1 h leptin levels were significantly higher (p < 0.001) in
      the nontreated patients (8.0 +/- 1.5) compared with those treated (5.15 +/- 0.9).
      CONCLUSION: These marked differences between treated and nontreated patients
      suggest that leptin levels may be modulated by a single antihypertensive
      treatment in preeclamptic patients with a discrete increase in blood pressure.

PMID- 11585976
TI  - Effect of naringin supplementation on cholesterol metabolism and antioxidant
      status in rats fed high cholesterol with different levels of vitamin E.
AB  - Some bioflavonoids are potent antioxidants and have pharmacological effects
      similar to those of vitamin E. The interactive effect of naringin and vitamin E
      was studied with respect to cholesterol metabolism and antioxidant status.
      Naringin supplementation (0.1%, wt/wt) with comparable levels of vitamin E was
      given to rats with a high-cholesterol (1%, wt/wt) diet for 5 weeks. The amount of
      vitamin E included in naringin-free and naringin diets was a low (low-E) and a
      normal (normal-E) level. The naringin supplementation significantly lowered the
      concentrations of plasma cholesterol and triglyceride compared to the naringin
      free group in low vitamin E-fed rats. HMG-CoA reductase activity was
      significantly lowered by naringin supplementation within both the low-vitamin E
      group (794.64 +/- 9.87 vs. 432.18 +/- 12.33 pmol/min/mg protein, mean +/- SE; p <
      0.05) and normal-vitamin E group (358.82 +/- 11.4 vs. 218.22 +/- 9.47 pmol/min/mg
      protein, mean +/- SE; p < 0.05) compared to each of the naringin-free group. The
      HMG-CoA reductase activity was also significantly lowered by increased dietary
      vitamin E when compared within the naringin and naringin-free group,
      respectively. Neither dietary naringin nor vitamin E did significantly change the
      activities of hepatic antioxidant enzymes and plasma thiobarbituric acid-reactive
      substance level. These data indicate that naringin lowers the plasma lipid
      concentrations when the dietary vitamin E level is low. The HMG-CoA reductase
      inhibitory effect of naringin was more potent when dietary vitamin E was at a
      normal level. These data may contribute to understanding the interactive effect
      of naringin and vitamin E on cholesterol biosynthesis in high-cholesterol-fed
      rats.

PMID- 11585977
TI  - Oral clearance and acid production of dairy products during interaction with
      sweet foods.
AB  - Oral clearance and acid production were observed in 30 volunteers following the
      ingestion of sharp cheddar cheese (CC) and in 9 volunteers following the
      ingestion of milk chocolate (MC) and low-fat yogurt, and then when MC was eaten
      immediately after CC (CC/MC) and when CC was eaten following MC (MC/CC). After
      each test food or food combination had been ingested the volunteers were
      monitored at five different tooth sites. At each site, using an absorbent paper
      point, 4 oral fluid samples were collected at 30 min intervals. The five paper
      points from each sampling occasion were pooled, extracted with 1 ml of water and
      analyzed qualitatively and quantitatively for both carbohydrates and organic
      acids using HPLC. Data obtained for each food was averaged and subjected to
      statistical evaluation. With the CC, glucose clearance was prolonged, due to
      intermediate lactose degradation into galactose and glucose. The quantity of
      lactic acid produced during the four intervals was monitored for each of the test
      foods and their combinations. RESULTS: CC, MC, CC/MC, MC/CC 30 min after
      ingestion: 1.64, 3.47, 4.68, 2.97; after 60 min: 1.30, 1.24, 1.28, 1.43; after 90
      min: 1.58, 1.02, 0.76, 0.43; after 120 min: 1.27, 0.90, 0.70, 0.42 mmol lactic
      acid/l oral fluid, respectively. The average total amount of lactic acid obtained
      during the two hour test period was (highest) CC/MC > MC > CC > MC/CC (lowest).
      The lowest amount of intra-oral lactic acid was observed (Student's t test, p <
      0.05) when cheddar cheese (CC) was eaten immediately after the milk chocolate
      (MC). CLINICAL SIGNIFICANCE: Consumption of cheese (cheddar), immediately after a
      sweet meal, significantly reduces (approx. 30%) the amount of lactic acid
      produced in the oral cavity, when compared to the amount of acid obtained from
      the sweet food alone.

PMID- 11585978
TI  - Fat absorption and metabolism in bile duct ligated rats.
AB  - BACKGROUND: Bile excretion is obstructed in children with extrahepatic bile duct
      atresia (EHBA) resulting in fat malabsorption and disturbed lipid metabolism.
      AIM: Investigate if the bile duct ligated rat exhibits similar deviations as
      patients with EHBA under different feeding conditions. METHODS: 6 bile duct
      ligated Wistar rats and 12 matched paired controls were randomised over 3 feeding
      groups. Rats were killed 16 or 30 days postsurgery. Faeces, blood and livers were
      collected. Fat absorption was evaluated, markers for cholestasis and the fatty
      acid composition of serum phospholipids (PL) and cholesterol esters (CE) were
      determined. Fatty acid desaturation activities in liver microsomes were measured.
      RESULTS: Cholestatic bile duct ligated rats have a lower fat absorption
      coefficient and a lower fraction of 18:2n-6 and 18:3n-3 in serum triglycerides
      than their controls. This demonstrates that bile duct ligated rats suffer from
      fat malabsorption. In contrast to the observations in serum triglycerides, 18:2n
      6 and 18:3n-3 were not reduced in serum PL and CE of cholestatic rats. Overflow
      of 18:2n-6 rich biliary PL in the general circulation could contribute to this
      observation. In agreement with what was found in man, serum PL of cholestatic
      rats have a higher 16:0/18:0 ratio, increased monoenes and reduced unsaturated
      fatty acids. However, no differences were observed in microsomal desaturation
      activities. CONCLUSION: Cholestatic bile duct ligated rats exhibit similar
      deviations in serum fatty acid composition as found in patients with EHBA,
      therefore they can be used as a model for this human disease.

PMID- 11585979
TI  - Phytoestrogens in Food and Bone Health. October 4-6, 2001, Versailles, France.
      Abstracts.

PMID- 11585980
TI  - Effect of tilting on cerebral hemodynamics in preterm and term infants.
AB  - Tilting is known to cause changes in hemodynamics due to hydrostatic pressure.
      The present study is an analysis of changes in cerebral hemodynamics measured by
      near infrared spectroscopy (NIRS) following tilting up and down in preterm and
      term infants. A significantly different effect of tilting up in comparison to
      tilting down on total hemoglobin in preterm infants and on the 'hemoglobin
      oxygenation index' in preterm and term infants was observed. In preterm infants,
      tilting up and down had a significantly different effect on cerebral blood volume
      (CBV), with an increase after tilting down and a decrease after tilting up. In
      term infants, tilting had no significant effect on CBV comparing these two
      procedures. We think that NIRS provides a good method to measure cerebral
      hemodynamics following tilting, whereby different reactions in infants of
      different postconceptional age can be observed.

PMID- 11585981
TI  - CD14 receptor expression and lipopolysaccharide-induced cytokine production in
      preterm and term neonates.
AB  - CD14 expression and the capacity of mononuclear cells (MC) from preterm and term
      neonates to secrete the proinflammatory cytokines interleukin (IL) 1 beta, tumor
      necrosis factor alpha and IL-6 in response to lipopolysaccharide (LPS) was
      investigated and compared to that of adults. MC were incubated with various doses
      of LPS, and the cytokine level in the supernatants was tested. CD14 receptors on
      MC and the intensity of their expression were analyzed. MC of preterm and term
      neonates and adults responded to LPS with low, medium and high proinflammatory
      cytokine production, respectively. CD14 expression was lowest in preterm infants,
      intermediate in term infants and highest in adults. The difference between term
      and preterm neonates for both parameters was significant. The results suggest a
      possible correlation between the lower expression of CD14 receptor on neonatal
      cells and the reduced secretion of proinflammatory cytokines by these cells. This
      decreased production may possibly contribute to the low ability of neonates to
      develop fever.

PMID- 11585982
TI  - Cytochrome P450 3A expression in the human fetal liver: evidence that CYP3A5 is
      expressed in only a limited number of fetal livers.
AB  - CYP3A is the major cytochrome P450 subfamily constitutively expressed in the
      human liver. CYP3A4 is the predominant hepatic P450 form in adults and it is
      expressed at high but very variable levels among individuals. The fetal liver
      contains mainly CYP3A7, while the presence of the other CYP3A enzymes in fetal
      liver has remained controversial. In this study, the relative levels of CYP3A4,
      CYP3A5 and CYP3A7 expression were determined in a panel of 9-11 fetal livers with
      a similar gestation age (9-12 weeks) and compared to adult livers. CYP3A7 was
      found to be the major CYP3A form in all the fetal liver samples. The abundance of
      CYP3A7 varied more at the mRNA (77-fold variation) than at the protein level (4.8
      fold variation). CYP3A5 mRNA was also detected in all of the fetal liver samples,
      but the average level was 700-fold lower than that of CYP3A7. CYP3A5 protein was
      detected by immunoblot analysis in only 1 fetal liver out of the 9 investigated,
      the level of expression being moderately high in this sample. CYP3A4 mRNA was
      detected in only a subset of the fetal liver samples and its level was the lowest
      of the CYP3A forms. This is the first study to demonstrate the polymorphic
      expression of CYP3A5 and the variability of CYP3A7 expression in fetal liver and
      suggests that significant interindividual differences in the metabolism of
      xenobiotics may already exist at the prenatal stage. These differences may
      contribute to individual pharmacological and/or toxicological responses in the
      fetus.

PMID- 11585983
TI  - The activity of collagen-degrading enzymes of Wharton's jelly in EPH gestosis
      (pre-eclampsia).
AB  - Oedema/proteinuria/hypertension (EPH) gestosis is one of the more common
      complications observed during pregnancy. Our previous studies demonstrated some
      qualitative and quantitative changes in the extracellular matrix of Wharton's
      jelly in newborns delivered by mothers with EPH gestosis. For this reason it was
      decided to evaluate the effect of EPH gestosis on the activity of gelatinolytic
      and proteolytic enzymes which may be involved in collagen degradation in
      Wharton's jelly. Zymographic analysis of control and EPH gestosis samples of
      Wharton's jelly demonstrates different electrophoretic patterns of gelatinolytic
      enzymes. The control Wharton's jelly contains two latent forms of gelatinolytic
      enzymes: gelatinase A [metalloproteinase (MMP)-2, 72 kD] and gelatinase B (MMP-9,
      92 kD). In contrast to control tissue, the main gelatinolytic enzyme of EPH
      gestosis Wharton's jelly is gelatinase A (MMP-2). It was found that the
      proteolytic activity in EPH gestosis Wharton's jelly differs from control. The
      decrease in gelatinase activity may be one of the factors which promote the
      accumulation of collagen in this tissue.

PMID- 11585984
TI  - Thyroid function in healthy and sick very-low-birth-weight infants--thyrotropin
      and free thyroxine levels until the sixth week of age.
AB  - Hypothyroxinemia in preterm infants without congenital hypothyroidism is
      associated with developmental delay. Longitudinal information on thyroid function
      in very-low-birth-weight (VLBW, <1,500 g birth weight) infants is limited: we
      present data on thyroid function in sick and healthy VLBW infants until 6 weeks
      of age. Free T(4) and TSH levels routinely obtained on days 14-21 and days 35-49
      in 92 consecutive VLBW infants were correlated retrospectively with neonatal
      morbidity. Free T(4) levels were positively correlated with gestational age; an
      independent effect of neonatal disease on thyroid function was not detectable.

PMID- 11585985
TI  - Expression and activity of the Ca(2+)-atpase enzyme in human neonatal
      erythrocytes.
AB  - The plasma membrane Ca(2+)-ATPase (PMCA) is one of the main regulators of Ca(2+)
      homeostasis. We studied the perinatal alteration of the abundance and the
      activity of PMCA molecules in human erythrocytes in pre-term and full-term
      neonates and children at the age of 1-4 years. The lower abundance of the 4b
      isoform was associated with lower enzyme activity in full-term neonates compared
      to children. Although the number of PMCA molecules was higher in pre-term
      neonates, their total PMCA activities were identical to those of full-term
      neonates. Our findings suggest that the abundance of PMCA molecules changes
      during the perinatal development. The same activity at higher enzyme molecule
      numbers might indicate a potential immaturity of the enzyme in the pre-term
      infant.

PMID- 11585986
TI  - Alcohol and breast feeding: calculation of time to zero level in milk.
AB  - OBJECTIVE: To create a nomogram that will guide lactating women who drink
      socially on how to avoid neonatal exposure to ethanol through breast milk.
      DESIGN: Pharmacokinetic modeling of ethanol elimination from milk based on
      reference values. Calculation of the time to zero alcohol in breast milk for a
      range of doses and body weights. RESULTS: The elimination of alcohol and time-to
      zero levels in breast milk are described in a nomogram as a function of the
      amount of alcohol consumed and the body weight of the woman. CONCLUSIONS: Careful
      planning of a breast feeding schedule, by storing milk before drinking and/or
      waiting for complete alcohol elimination from the breast milk, can ensure women
      that their babies are not exposed to any alcohol.

PMID- 11585987
TI  - Alterations in lymphocyte phenotype of infected preterm newborns.
AB  - The cord blood lymphocytes from 44 premature newborns were analyzed using two
      color monoclonal antibodies and flow cytometry. Depending on whether or not there
      was an infection at birth, the newborns were divided into two groups and the
      immunophenotypes of infected and uninfected newborns were compared. The
      percentage of T lymphocytes (CD3+) was significantly lower in the infected
      prematures. The percentage of both helper and cytotoxic T lymphocytes was lower.
      The proportion of activated T lymphocytes, cytotoxic non-MHC-restricted T
      lymphocytes, NK cells and B lymphocytes did not differ between the group of
      infected and the group of uninfected prematures. The percentage of memory helper
      T lymphocytes (CD45RO+CD4+) was very low in premature newborns regardless of
      whether or not they were infected and could not be used as a marker of bacterial
      infection at this age.

PMID- 11585988
TI  - Liver lipid accumulation in duck embryos and hatchlings change with parental age.
AB  - The purpose of this study was to investigate the effects of duck breeder age on
      liver lipid accumulation and yolk absorption and utilization in duck embryos (day
      25 of incubation) and newly hatched ducklings. One breeder flock was monitored at
      24 (young breeders), 31 (mature breeders and near peak egg production) and 47
      (post peak egg production) weeks of age. Electron microscopy images of duck
      embryo liver slices revealed a significant change in hepatic lipid accumulation
      as a function of breeder age. More specifically, as breeder age increased both
      the relative number of liver lipid droplets as well as the size of the lipid
      droplets increased in duck embryos (day 25 of incubation). At hatch, however,
      newly hatched ducklings from 31-week-old breeders exhibited the lowest number as
      well as the smallest sized lipid droplets when compared to ducklings from 24 or
      47-week-old breeders. The trend in yolk absorption at day 25 as a function of
      breeder age paralleled that in liver lipid accumulation. That is, day 25
      maintained a higher percentage of unabsorbed yolk when compared to embryos from
      31- or 47-week-old breeders. In contrast to breeder age, time of incubation (day
      25 vs. day 28 or hatch) had little effect on yolk fatty acid profiles when
      compared to breeder age. Although there were no clear trends in yolk fatty acid
      usage among the various ages of breeders, newly hatched ducklings from 31-week
      old breeders did have a significantly higher proportion of 18:2 n6 compared to
      those from breeders at 24 or 47 weeks of age. These data would suggest that
      breeder age subsequently affects the relative number and size of liver lipid
      droplets in embryos and newly hatched ducklings.

PMID- 11585989
TI  - Age-dependent effect of domperidone on dopamine release by the hypoxic carotid
      body in the rabbit.
AB  - The aim of this study was to identify the mechanisms that regulate dopamine
      release (DA(r)) by the hypoxic carotid body (CB) during development. CBs sampled
      from adult (n = 58) and 10-day-old (n = 53) rabbits were incubated for 1 h in a
      medium equilibrated with 8% O(2) in N(2) without or in the presence of the
      specific DA D(2) receptor antagonist domperidone, 0.01, 0.1 and 1 microM. DA and
      its major metabolite DOPAC were measured in the CB (DA(CB)) and in the medium
      (DA(r)) by HPLC+ED. In adults, each concentration of domperidone significantly
      decreased DA(CB) and increased DA(r), compared with control (p < 0.01). In
      contrast, in 10-day old, only the 1 microM domperidone concentration decreased
      DA(CB) and increased DA(r) compared with control (p < 0.001). The data show that
      domperidone increases CB DA(r) in response to hypoxia in a concentration- and age
      dependent manner and suggest this response depends, in part, on the functional
      maturation of CB DA D(2) receptors.

PMID- 11585990
TI  - Regional Brazilian diet-induced low birth weight is correlated with changes in
      renal hemodynamics and glomerular morphometry in adult age.
AB  - Number of nephrons, renal hemodynamics, and glomerular morphometry were assessed
      in rats submitted to a multideficient diet which was developed from a basic
      regional diet consumed in a Brazilian region of sugarcane cultivation. We
      evaluated three groups of male Wistar rat offspring: (1) from dams fed a standard
      diet throughout mating, pregnancy and lactation (control group) and (2) from dams
      fed the multideficient diet during mating and pregnancy (MalN1 group) or (3)
      throughout mating, pregnancy, and lactation (MalN2 group). At adult age, the
      animals were anesthetized to measure mean arterial blood pressure and renal
      hemodynamics. The MalN1 group, as compared with the control group, showed
      unaltered body and kidney weights, nephron deficiency, a high mean arterial blood
      pressure, glomerular hypertrophy, and renal vasoconstriction. The MalN2 group
      showed the same nephron deficiency and mean arterial blood pressure levels as the
      MalN1 group. These animals exhibited lower body and kidney weights and no
      glomerular hypertrophy. In conclusion, the alterations induced by intrauterine
      malnutrition are compatible with the development of chronic renal failure.

PMID- 11585991
TI  - Chronic exposure to cigarette smoke extract impairs endothelium-dependent
      relaxation of chicken embryo pulmonary arteries.
AB  - Maternal smoking may increase the risk for various adverse neonatal outcomes
      including persistent pulmonary hypertension of the newborn (PPHN). We
      investigated whether chronic prenatal cigarette smoke extract (CSE) exposure
      could produce abnormal vasoreactivity in pulmonary arteries. Daily injections of
      CSE (diluted in phosphate buffered saline) or vehicle were added to the air cells
      of fertilized eggs starting on day 5 of the 21-day incubation period of the
      chicken embryo. On day 19, pulmonary arteries were dissected out and their
      contractile properties were assessed using small vessel myography. Endothelium
      dependent and endothelium-independent vasorelaxations were examined by using
      acetylcholine (ACh, 10(-8) to 10(-4) M) and sodium nitroprusside (SNP, 10(-8) to
      10(-4) M), respectively. The drug concentration inducing 50% of the maximal
      relaxation was determined for each concentration-response curve and expressed as
      negative log molar (pD(2)). Exposure to CSE significantly decreased the
      sensitivity of pulmonary arteries to ACh (pD(2) control group: 7.29 +/- 0.24;
      pD(2) CSE-exposed group 6.24 +/- 0.12, p < 0.05). SNP elicited similar responses
      in vessels of both groups at all tested concentrations. In conclusion, chronic
      prenatal exposure to CSE impaired endothelium-dependent but not endothelium
      independent vasodilation in chicken embryo pulmonary arteries. This observation
      suggests that cigarette smoke components may produce deleterious effects on fetal
      vascular endothelial vasorelaxant pathways, leading to the development of adverse
      outcomes such as PPHN.

PMID- 11585993
TI  - Coronary artery calcium determined by electron beam computed tomography for
      predicting angiographic coronary artery disease in moderate- to high-risk Chinese
      patients.
AB  - The aim of this study was to evaluate the prevalence of coronary calcification
      among moderate- to high-risk Chinese patients and to evaluate the ability of the
      coronary calcium score determined by electron beam computed tomography (EBCT) to
      predict angiographic coronary artery disease in this population. We enrolled 163
      consecutive patients and analyzed their cardiovascular risk factors, coronary
      calcium scores and coronary angiogram results. One hundred and twenty-five
      patients (76.7%) had a positive EBCT scan result (coronary calcium score >0). The
      prevalence of calcification and the calcium scores showed a graded relation to
      the number of cardiovascular risk factors and age (p < 0.001 for trend). Coronary
      calcium scores showed statistically significant differences between patients with
      angiographic evidence of coronary artery disease and patients with normal
      coronary angiography (p < 0.05), but could not differentiate between patients
      with significant and insignificant coronary artery disease. Receiver operating
      characteristic curve analysis showed that a coronary calcium score >5 predicted
      angiographic coronary artery disease with 93% sensitivity and 86% specificity
      (area under the curve 0.95 +/- 0.019). Multivariate analysis showed a coronary
      calcium score >5 to be the strongest independent predictor of angiographic
      coronary artery disease (odds ratio 120.7, 95% confidence interval 21.7-671.4; p
      < 0.001). Coronary calcium score determined by EBCT appears to have a similar
      predictive value in Chinese patients as it does in other ethnic populations that
      have been reported to date.

PMID- 11585992
TI  - Impact of acute biventricular pacing on left ventricular performance and volumes
      in patients with severe heart failure. A tissue doppler and three-dimensional
      echocardiographic study.
AB  - OBJECTIVES: We used tissue velocity imaging (TVI) and three-dimensional
      echocardiography to evaluate the effect of acute biventricular pacing on left
      ventricular (LV) performance and volumes in patients with severe heart failure
      and bundle branch block. BACKGROUND: Biventricular pacing causes acute
      hemodynamic improvement in patients with severe heart failure, and QRS duration
      has been used as a predictor of improved resynchronization. Tissue velocity has
      the potential of demonstrating the degree of LV resynchronization and three
      dimensional echocardiography enables accurate quantitation of LV volumes and
      function. METHODS: TVI and three-dimensional echocardiography were performed
      during sinus rhythm and biventricular pacing in 25 consecutive patients with
      severe heart failure. RESULTS: Biventricular pacing significantly improved the
      extent of contracting myocardium in synchrony by 15.4% and the duration of
      contraction synchrony by 17% (p < 0.05 for both). Furthermore, end-diastolic and
      end-systolic volumes decreased by 7 +/- 4.5% and 13 +/- 6% (p < 0.01) and
      ejection fraction increased by 22.8 +/- 9% (p < 0.01). Baseline duration of QRS
      and the preejection period as well as the extent of myocardium with asynchronous
      contraction measured by TVI predicted pacing efficacy. In multivariate analysis,
      only the extent of myocardium with asynchronous contraction at the LV base
      predicted biventricular pacing efficacy. CONCLUSION: Biventricular pacing
      improves LV systolic performance and reduces LV volumes during short-term
      treatment. TVI provides important pathophysiological information on the degree of
      LV resynchronization and may contribute to improved patient selection.

PMID- 11585994
TI  - Prognostic implications of left ventricular diastolic dysfunction with preserved
      systolic function following acute myocardial infarction.
AB  - The contribution of diastolic dysfunction in patients with preserved left
      ventricular (LV) systolic function to impaired functional status and cardiac
      mortality in myocardial infarction (MI) is unknown. In the present study,
      assessment of LV diastolic function was performed by Doppler analysis of the
      mitral and pulmonary venous flow, and the propagation velocity of early mitral
      flow by color M-mode Doppler echocardiography in 183 consecutive patients at day
      5-7 following their first acute MI. Patients were classified into four groups:
      group A: preserved LV systolic and diastolic function (n = 73); group B: LV
      systolic dysfunction with preserved diastolic function (n = 10); group C: LV
      diastolic dysfunction with preserved systolic function (n = 60); group D:
      combined LV systolic and diastolic dysfunction (n = 40). The cardiac mortality
      rate at 1 year was significantly higher in groups C (13%) and D (38%) compared to
      A (2%) (p < 0.01). Multivariate regression analysis identified LV diastolic
      dysfunction (p = 0.001), Killip class >or=II (p = 0.006), and age (0.008) as
      predictors of cardiac death or readmission due to heart failure. The presence of
      LV diastolic dysfunction with preserved systolic dysfunction is associated with
      increased morbidity and mortality following acute MI.

PMID- 11585995
TI  - High-speed rotational atherectomy in the treatment of bifurcation-type coronary
      lesions.
AB  - BACKGROUND: Bifurcational coronary lesions present a major interventional
      challenge. The differential cutting mechanism of high-speed rotational
      atherectomy (HSRA) may provide a favourable technique of treating this complex
      lesion subtype. METHODS: We evaluated the use of HSRA (32 lesions) compared to
      balloon angioplasty (BA) (118 lesions), with provisional stenting in both groups,
      in a non-randomised, retrospective study of 150 bifurcation-type lesions.
      RESULTS: The HSRA/stent group had a high primary success rate of 97%, an
      acceptably low in-hospital event rate of 9% and an overall major adverse cardiac
      event (MACE) rate at a mean follow-up period of 15 +/- 3.4 months of 22.5% with a
      target lesion revascularisation (TLR) rate of 18.7%. Procedural success in the
      BA/stent group was 81% with an in-hospital event rate of 14.4%, and the overall
      MACE rate at follow-up was 27.5% with a TLR rate of 23%. We achieved a greater
      acute gain in minimal luminal diameter and a lesser percentage of residual
      stenosis after intervention in the HSRA/stent group compared to the BA/stent
      group (p < 0.01). Outcome at follow-up favoured the HSRA/stent group, although
      the difference did not reach statistical significance. CONCLUSION: HSRA with
      provisional stenting provided a safe and effective means of treating bifurcation
      lesions.

PMID- 11585996
TI  - Serum leptin levels increase following acute myocardial infarction.
AB  - Leptin is secreted into the circulation and communicates the peripheral
      nutritional status to specific hypothalamic centers. Recent studies suggest that
      leptin may be involved in the acute response to stress, and that its interaction
      with the hypothalamo-pituitary-adrenal axis and the inflammatory cytokine system
      may be of clinical importance. Since these systems are activated during acute
      myocardial infarction (AMI), we studied leptin and cortisol levels during
      hospitalization in 30 consecutive patients admitted for AMI. The results show
      that leptin reached its peak on the second day of hospitalization, with a 2-fold
      increase from its baseline level on admission (p < 0.02). On day 3, leptin levels
      declined, and were 46%, 9%, and 6% above baseline on days 3, 4 and 5,
      respectively. The mean cortisol level was elevated on day 1 and decreased toward
      normal levels thereafter (p < 0.001). The cortisol level did not correlate with
      leptin concentration throughout the study. These findings suggest that leptin may
      have a role in the metabolic changes taking place during the first days after an
      AMI.

PMID- 11585997
TI  - Mechanical trauma as the major cause of troponin T release after transvenous
      implantation of cardioverter/defibrillators.
AB  - To study the cause of myocardial injury after elective transvenous insertion of a
      cardioverter/defibrillator, we measured troponin T (TnT) release in 27 patients.
      Five patients needing only replacement of the generator with threshold testing
      served as controls. Compared to the control group, a significant increase in TnT
      occurred in the patients undergoing insertion, which was greatest in the group
      receiving screw-in electrodes. There was no correlation between TnT and the
      number and energy of the shocks and the time in fibrillation. Duration of surgery
      and TnT release were positively associated. Cardiac injury therefore mainly
      results from mechanical trauma during insertion of the electrodes and only to a
      lesser degree from electrical and ischemic lesions.

PMID- 11585998
TI  - Acute profound thrombocytopenia associated with anaphylactic reaction after
      abciximab therapy during percutaneous coronary angioplasty.

PMID- 11586000
TI  - Solutions for difficult diagnostic cases of community-acquired pneumonia.
AB  - Community-acquired pneumonia (CAP) is a common illness that creates significant
      burdens upon the healthcare system. Improving the quality of medical care for
      patients with this illness requires an evidence-based and cost-efficient
      treatment approach. The first step in this approach is to make an accurate
      diagnosis, while considering the full differential diagnosis of the illness. This
      requires an understanding of the sensitivity and specificity of the history and
      physical examination to establish the diagnosis of CAP. The second step is to
      quantify severity of illness, which can help physicians determine the appropriate
      initial site of treatment, intensity of the diagnostic evaluation, and choice of
      initial antibiotic therapy. Case histories are presented to outline the clinical
      application of an approach that uses the Pneumonia Patient Outcomes Research Team
      (PORT) prediction rule for prognosis to quantify the severity of illness, and
      recent guidelines for the management of CAP are highlighted.

PMID- 11586001
TI  - Optimal treatment strategies for community-acquired pneumonia: non-responders to
      conventional regimens.
AB  - When patients with community-acquired pneumonia (CAP) fail to respond after
      initiation of empirical therapy, it is necessary for the physician to consider a
      number of possibilities. The diagnosis should be reviewed, with consideration
      given to both non-infectious and infectious illnesses. If the diagnosis is
      correct, the failure may relate to three areas: host-related problems, including
      overwhelming infection and empyema, pathogen-related problems, including
      infection caused by an unusual or resistant pathogen, and drug-related problems,
      including inappropriate dose of drug, poor compliance, malabsorption, and drug
      interactions. A systematic therapeutic approach including a microbiological
      evaluation to identify the causative pathogen and its susceptibility will help to
      ensure that an appropriate antimicrobial agent is used.

PMID- 11586002
TI  - Optimal treatment strategies for community-acquired pneumonia: high-risk patients
      (geriatric and with comorbidity).
AB  - The four major factors predisposing individuals to community-acquired pneumonia
      (CAP) are chronic obstructive pulmonary disease, congestive heart failure,
      diabetes, and a high alcohol intake. The elderly are also at increased risk of
      severe infection. The introduction of fluoroquinolones with increased activity
      against Streptococcus pneumoniae and other CAP pathogens has been an important
      development, with recent guidelines recommending the use of respiratory
      fluoroquinolones as a first-line choice in outpatients with modifying factors,
      nursing home residents, and hospitalised patients in medical wards. Of the
      fluoroquinolones currently available that have antipneumococcal activity,
      levofloxacin is well tolerated and effective. It has been approved by the Food
      and Drug Administration (FDA) for treatment of CAP and widespread use has shown
      it to be very safe.

PMID- 11586003
TI  - Solutions for difficult diagnostic cases of acute exacerbations of chronic
      bronchitis.
AB  - Acute exacerbation of chronic bronchitis (AECB) is a very common condition, which
      presents with deteriorating sputum production and dyspnoea in a patient with pre
      existing COPD or chronic bronchitis. As these symptoms are relatively non
      specific and also the presenting feature of a wide range of other conditions, the
      physician should carefully consider the differential diagnosis before deciding on
      whether or not a patient indeed has AECB. The differential diagnosis can be
      summarised as pneumonia, pneumothorax, cardiac failure/cor pulmonale,
      bronchiectasis, asthma, tuberculosis, sinusitis and other forms of upper
      respiratory tract sepsis, diffuse panbronchiolitis, lung cancer, gastro
      oesophageal reflux, the presence of a foreign body in the airway, melioidosis,
      and lung abscess. This article aims to discuss these conditions, with brief
      presentation of clinical cases, in the evaluation of differential diagnosis of
      AECB.

PMID- 11586004
TI  - Management of clinical failures in non-ICU patients with chronic obstructive
      pulmonary disease exacerbations.
AB  - Clinical failure after initial treatment for exacerbations of chronic obstructive
      pulmonary disease (COPD) occurs in 10-25% of cases. Once the original diagnosis
      is confirmed, there is a need to optimise therapy, including introducing
      bronchodilators and corticosteroids. The use of aggressive antibiotic treatment
      is recommended for patients with risk factors (elderly, more than four
      exacerbations per year, underlying cardiopulmonary disease) and more severe
      disease. Fluoroquinolones are a good choice for those patients who failed initial
      therapy and who require antimicrobials, including those with simple
      exacerbations, complicated cases with comorbidity, or those with bronchiectasis.
      Consideration of less common pathogens, such as Pseudomonas aeruginosa infection,
      should also be considered. Bacteria usually associated with exacerbations are
      becoming increasingly resistant, and this needs to be considered when deciding on
      appropriate antibiotic treatment.

PMID- 11586005
TI  - Optimal treatment strategies for acute exacerbations of chronic bronchitis: high
      risk patients.
AB  - Diagnosis of high-risk patients with acute exacerbations of chronic bronchitis
      (AECB) should include an evaluation of the patient's respiratory function, chest
      X-ray to exclude pneumonia, and sputum culture. Increasing resistance to
      amoxicillin, cephalosporins, macrolides, trimethoprim-sulfamethoxazole, and
      doxycycline means that fluoroquinolones are often the only oral empiric treatment
      available. Levofloxacin, a new respiratory fluoroquinolone with a wide spectrum
      of antibacterial activity and no cross-resistance with other classes of
      antibiotics, can be administered as an intravenous formulation as well as orally.
      Sequential therapy is easily administered due to its high oral bioavailability,
      and the dosing schedule can be a convenient once-daily dose. Clinical trials have
      established that levofloxacin is effective in AECB and is well tolerated.

PMID- 11586007
TI  - Teloptosis, a turning point in hair shedding biorhythms.
AB  - The timing regulation of the hair growth phases is quite complex. We name
      teloptosis the termination of the telogen phase with hair shedding. The
      initiation of the next anagen I phase is independent from teloptosis. Both events
      are triggered by distinct factors. Indeed, teloptosis is the result of the loss
      of adhesion between cells of the club hair and those of its epithelial envelope.
      Teloptosis synchronization is perceived as telogen effluvium, related or not to
      shortening of the anagen phase. Subtle changes leading to early or delayed
      teloptosis affect hair density. It is possible to distinguish two types of
      telogen hairs on a trichogram. Those with an epithelial sheath indicate strong
      binding, suggesting early telogen, whereas the absence of an epithelial sheath
      indicates loose binding, conveying teloptosis.

PMID- 11586008
TI  - Cazenave, Kaposi and lupus erythematosus. A centennial and a sesquicentennial.
AB  - A review is presented calling attention to the first naming and publication of
      the term 'lupus erythematosus' and to the dermatologist (M. Kaposi) who first
      detected the systemic nature of this disease.

PMID- 11586009
TI  - Topical metronidazole does not abate UVB-induced erythema.
AB  - BACKGROUND: The capacity of topical metronidazole to reduce erythema severity
      scores in rosacea has been attributed to its anti-inflammatory activity. METHODS:
      Nine healthy subjects were irradiated on three 1-cm(2) areas on their volar
      forearm with 2 MEDs of UVB. Twenty-four hours later, one of the irradiated areas
      was treated daily with metronidazole 1% vanishing cream, one with the vehicle
      only and the third was left untreated (control). The intensity of erythema was
      measured, at 24, 48, 72 and 96 h after irradiation, by a Chromameter CR200
      (Minolta, Japan) and expressed in the L*a*b* system. The a* parameter was taken
      as the measure of redness. RESULTS: Overall, redness diminished over time in a
      linear way, but treatments did not influence it significantly. CONCLUSION: In our
      vehicle, metronidazole 1% cream failed to abate the UVB-induced erythema. An
      activity other than the anti-inflammatory one should be suggested to explain the
      topical metronidazole efficacy in rosacea.

PMID- 11586010
TI  - Psychosocial impact of acne vulgaris. evaluation of the relation between a change
      in clinical acne severity and psychosocial state.
AB  - BACKGROUND: Although knowledge concerning the impact of acne vulgaris on quality
      of life has increased in recent years, relatively few studies have assessed the
      effect of a change in clinical severity on psychosocial state. OBJECTIVE:
      Assessment of the effect of a change in clinical acne severity on psychosocial
      state. METHODS: This was investigated by means of questionnaires and clinical
      assessments by acne patients and dermatologists. Fifty females with mild to
      moderate facial acne were seen before and after a 9-month treatment with oral
      contraceptives. RESULTS: The results showed a great variability in psychosocial
      impairment between individuals. After 9 months, a significant reduction in
      clinical severity was seen overall which did not relate to the significant
      improvements in self-esteem, stability of self-esteem and acceptance of
      appearance. CONCLUSION: Perceived psychosocial impairment is individually based,
      is greater in women who subjectively overrate their acne and does not relate to
      clinical improvement.

PMID- 11586011
TI  - Basal cell carcinoma on the vermilion border of the lip: a study of six cases.
AB  - BACKGROUND: The vermilion border of the lower lip is a frequent location of
      squamous cell carcinoma (SCC), but it is very rarely mentioned within the
      published series of basal cell carcinomas (BCCs). OBJECTIVE: We present 6 cases
      of BCC involving either mainly or exclusively the vermilion border of a lip.
      METHODS: We reviewed from our files all the cases of BCC diagnosed in a period of
      11 years. RESULTS: A number of 3,477 BCCs were histologically diagnosed in that
      period; 2,872 (82.6%) of them were located on the head, and 66 (2.3%) of the
      latter (1.9% of all BCCs) were on the lips. In 6 cases, the neoplasm involved
      either mainly or exclusively the vermilion border of either the lower (5 cases)
      or the upper (1 case) lip. CONCLUSION: Not every carcinoma of the vermilion
      border of the lip is a SCC.

PMID- 11586012
TI  - Multicenter randomized comparative double-blind controlled clinical trial of the
      safety and efficacy of zinc gluconate versus minocycline hydrochloride in the
      treatment of inflammatory acne vulgaris.
AB  - BACKGROUND: In addition to tetracyclines, zinc may constitute an alternative
      treatment in inflammatory lesions of acne. OBJECTIVE: To evaluate the place of
      zinc gluconate in relation to antibiotics in the treatment of acne vulgaris.
      METHODS: Zinc was compared to minocycline in a multicenter randomized double
      blind trial. 332 patients received either 30 mg elemental zinc or 100 mg
      minocycline over 3 months. The primary endpoint was defined as the percentage of
      the clinical success rate on day 90 (i.e. more than 2/3 decrease in inflammatory
      lesions, i.e. papules and pustules). RESULTS: This clinical success rate was
      31.2% for zinc and 63.4% for minocycline. Minocycline nevertheless showed a 9%
      superiority in action at 1 month and one of 17% at 3 months, with respect to the
      mean change in lesion count. Regarding safety, the majority of the adverse
      effects of zinc gluconate and of minocycline concerned the gastrointestinal
      system and were moderate (5 dropouts with zinc gluconate and 4 with minocycline).
      CONCLUSION: Minocycline and zinc gluconate are both effective in the treatment of
      inflammatory acne, but minocycline has a superior effect evaluated to be 17% in
      our study.

PMID- 11586013
TI  - Vitamin B(12) cream containing avocado oil in the therapy of plaque psoriasis.
AB  - BACKGROUND: There are already many effective topical therapies available for use
      in the treatment of chronic plaque psoriasis. Unfortunately, these treatments are
      often associated with a rather significant risk of undesirable effects. OBJECTIVE
      AND METHODS: In this randomized, prospective clinical trial, the effects of the
      vitamin D(3) analog calcipotriol were evaluated against those of a recently
      developed vitamin B(12) cream containing avocado oil in an intraindividual
      right/left-side comparison. The trial population consisted of 13 patients, 10 men
      and 3 women, with chronic plaque psoriasis. The observation period was 12 weeks;
      the effects of therapy were assessed on the basis of a PASI score adapted to the
      right/left-side comparison technique, the subjective evaluations of the
      investigator and patients and the results of 20-MHz sonography. RESULTS: There
      was a more rapid development of beneficial effects with the use of calcipotriol
      in the initial 8 weeks, although differences in effects were significant only at
      the time point of therapy week 8 (p < 0.05). After 12 weeks, neither the PASI
      score nor 20-MHz sonography showed significant differences between the two
      treatments. While the efficacy of the calcipotriol preparation reached a maximum
      in the first 4 weeks and then began to subside, the effects of the vitamin B(12)
      cream containing avocado oil remained at a constant level over the whole
      observation period. This would indicate that the vitamin B(12) preparation
      containing avocado oil may be suitable for use in long-term therapy, a hypothesis
      further supported by the fact that the investigator and the patients assessed the
      tolerability of the vitamin B(12) cream containing avocado oil as significantly
      better in comparison with that of calcipotriol. CONCLUSION: The results of this
      clinical trial provide evidence that the recently developed vitamin B(12) cream
      containing avocado oil has considerable potential as a well-tolerated, long-term
      topical therapy of psoriasis.

PMID- 11586014
TI  - Treatment of psoriasis with a new combination of calcipotriol and betamethasone
      dipropionate: a flow cytometric study.
AB  - BACKGROUND: Calcipotriol and corticosteroids are established topical
      antipsoriatics. Previous studies have shown that combined therapy with
      calcipotriol and betamethasone dipropionate was more effective than monotherapy.
      In the present study, a recently developed combination product of calcipotriol
      and betamethasone dipropionate was compared with both monotherapies and the
      vehicle. METHODS: Twenty-five psoriatic patients were treated twice daily with
      the combination product, monotherapy or vehicle during 4 weeks. Skin biopsies,
      taken before and after treatment, were analysed using a multi-parameter flow
      cytometric method. Parameters of inflammation (vimentin-positive cells), normal
      differentiation (keratin-10-positive cells) and proliferation (cells in SG(2)M
      phase) were assessed. RESULTS: Flow cytometric analysis showed that the
      combination product turned out to be more effective in reducing inflammation
      compared with the other treatments. Restoration of normal differentiation was
      more advanced in patients treated with the combination product or betamethasone
      dipropionate compared to the vehicle. The highest number of normally
      differentiated cells was seen after use of the combination product. All
      treatments, except for the vehicle, decreased hyperproliferation. CONCLUSIONS
      This study shows that the combination product is a valuable new approach to the
      treatment of psoriasis.

PMID- 11586015
TI  - Calcipotriol solution for the treatment of scalp psoriasis: evaluation of
      efficacy, safety and acceptance in 3,396 patients.
AB  - BACKGROUND: Psoriasis of the scalp is a very common disease, cosmetically
      disturbing and therapeutically difficult to manage. OBJECTIVE: The aim of our
      study was to investigate the efficacy, safety and cosmetic acceptance of
      calcipotriol solution in a large number of patients with mild to moderate scalp
      psoriasis and to compare this treatment with previous therapies used. METHODS: In
      this multicentre prospective observational cohort study 3,396 patients were
      treated with calcipotriol solution (50 microg/ml) twice daily over an 8-week
      period either alone or in combination with other treatments. The psoriasis scalp
      severity index (PSSI) and investigator/patient global assessment were used for
      the evaluation of clinical response. RESULTS: All psoriasis severity parameters
      measured were reduced with a significant decrease in PSSI scores from 18.4 to 5.6
      after 8 weeks of therapy (p < 0.001). About 80% of the patients showed very good
      or good clinical improvement. Combination of calcipotriol solution with other
      treatment modalities e.g. corticosteroids or salicylic acid, showed an increased
      treatment response. In only 2.4% of the patients side effects occurred (e.g.
      irritation). CONCLUSION: Calcipotriol solution is an effective, safe, well
      tolerated and cosmetically acceptable treatment modality. By patients and
      physicians, this treatment was found to be a valuable supplement to previously
      available and established treatments for scalp psoriasis.

PMID- 11586016
TI  - Alopecia areata and affected skin CRH receptor upregulation induced by acute
      emotional stress.
AB  - BACKGROUND: Recent evidence indicates that acute stress can precipitate a number
      of dermatological conditions, including alopecia areata. This effect may be
      mediated by corticotropin-releasing hormone (CRH) released locally in the skin
      from dorsal root ganglia or immune cells. CRH typically acts through activation
      of specific receptors that are either type 1 or types 2 alpha and 2 beta. CRH, or
      related peptides such as urocortin, could have proinflammatory effects directly
      or through activation of mast cells leading to destruction of the hair root.
      OBJECTIVES: To investigate the expression of CRH receptors on the affected skin
      of patients who developed alopecia areata following acute emotional stress.
      METHODS: Scalp skin biopsies were obtained from 1 normal volunteer and 3 patients
      after ring infiltration of the relevant site with lidocaine. The biopsies were
      frozen and were later processed for in situ hybridization for CRH receptors type
      1 or types 2 alpha and 2 beta. Sections showing positive results were
      photographed. RESULTS: The skin from the normal volunteer showed weak background
      expression of all three receptor types. However, skin from the affected sites of
      all 3 patients studied showed intense expression only on the type 2 beta receptor
      around the hair follicles. CONCLUSION: Acute emotional stress may precipitate
      alopecia areata by activation of overexpressed type 2 beta CRH receptors around
      the hair follicles leading to intense local inflammation.

PMID- 11586017
TI  - Primary hyperparathyroidism and cutaneous T-cell lymphoma: fortuitous
      association?
AB  - This is the third report of an association between T-cell cutaneous lymphoma
      (mycosis fungoides) and primary hyperparathyroidism (adenoma). Some studies
      support the concept that hyperparathyroidism may have promotional activity for
      the development of certain malignant tumors. A high risk for successive or
      concurrent neoplasms has been reported in patients with parathyroid adenomas.
      Primary hyperparathyroidism in a neoplastic context may be underreported.
      Patients with tumor-associated hypercalcemia should be evaluated for the
      possibility of primary hyperparathyroidism.

PMID- 11586018
TI  - Large B-cell lymphoma of the leg--complete remission with perilesional interferon
      alpha.
AB  - We present the case of an 85-year-old woman with cutaneous and subcutaneous
      nodules on the lower and upper leg showing the characteristic histological
      features of a large B-cell lymphoma of the leg. Investigations for non-Hodgkin's
      lymphoma with the prognostic markers matrix metalloproteinase 2 and soluble
      intercellular adhesion molecule 1 revealed an increased serum level of the
      latter. Monotherapy with perilesional interferon alpha(2a) 3 x 9 million
      units/week was well tolerated. The final outcome was a complete remission after
      14 months with an overall survival of more than 17 months.

PMID- 11586019
TI  - Multilesional primary cutaneous diffuse large B-cell lymphoma responsive to
      antibiotic treatment.
AB  - Borrelia burgdorferi infection has been implicated in cutaneous B-cell lymphoma.
      We report a case of multilesional primary cutaneous large B-cell lymphoma without
      extracutaneous spread in a patient with elevated B. burgdorferi titers. After
      antibiotic therapy, clinical remission and a subsequent drop in B. burgdorferi
      antibody titers were obtained.

PMID- 11586020
TI  - Acute genitocrural intertrigo: a sign of primary human immunodeficiency virus
      type 1 infection.
AB  - We describe a 49-year-old male patient who presented with an acute illness
      associated with a widespread maculopapular eruption and eroded lesions in the
      inguinal folds consistent with an acute intertrigo, for which search of
      mycological and bacteriological causes remained negative. Serological tests
      disclosed a high viral HIV-1 load and p24 antigenemia, while anti-HIV-1
      antibodies were absent, a profile typical of acute HIV-1 infection. Since the
      maculopapular eruption regressed concomitantly with the orogenital lesions as
      well as the eroded inguinal lesions prior to specific therapy, our observation
      indicates that intertriginous lesions may constitute one of the early cutaneous
      markers of primary HIV-1 infection.

PMID- 11586021
TI  - A Case of pemphigus foliaceus which occurred after five years of remission from
      pemphigus vulgaris.
AB  - A 77-year-old Japanese female developed pemphigus foliaceus (PF) after 5 years of
      remission from pemphigus vulgaris (PV). The patient had painful erosions in her
      mouth and flaccid blisters of the skin and was diagnosed as having PV, which
      responded well to corticosteroid treatment. She was then free from any lesion of
      PV for 5 years with a low dose of corticosteroid. Then she developed scaly
      erythematous lesions on the skin and was diagnosed as suffering from PF. Enzyme
      linked immunosorbent assay (ELISA) using recombinant desmoglein 1 (Dsg-1) and Dsg
      3 revealed that she had anti-Dsg-3 IgG in the PV stage, no antibodies during
      remission and anti-Dsg-1 IgG in the PF stage. These findings indicate that the
      target antigen was shifted from Dsg-3 to Dsg-1 along with the phenotype after a 5
      year interval in this patient.

PMID- 11586022
TI  - Polishing-paste-induced silica granuloma of the gingiva.
AB  - Polishing-paste-induced silica granuloma of the gingiva, an uncommon condition,
      may mimic various local or systemic pathological entities. A 33-year-old woman
      and a 42-year-old man were referred for a localised refractory gingival
      inflammation. Clinical diagnoses included allergy, lichen planus and herpes.
      Biopsy showed well-demarcated non-caseating granulomas, associating epithelioid
      and Langhans giant cells. Special bacterial and mycological stains were negative.
      Systemic examination and laboratory tests ruled out sarcoidosis and Crohn's
      disease. Polarised light revealed birefringent crystalline foreign material. A
      diagnosis of silica granuloma was made. Both patients had frequent dental hygiene
      treatment including polishing with abrasive paste, suggesting an iatrogenic
      implantation of the foreign bodies. Gingival damage can result from the use of
      some dental materials containing silica. Often asymptomatic, sometimes producing
      visible lesions, granulomatous gingivitis may mislead into wrong diagnosis and
      treatment. Old silica granulomas may become symptomatic if the patient contracts
      sarcoidosis.

PMID- 11586023
TI  - Proteus syndrome.
AB  - A case of Proteus syndrome is presented, in which severe hemihypertrophy of the
      left trunk and left lower extremity, scoliosis, endometriosis and huge bizarre
      shaped body tumors were observed. Up to 22.6 kg of tumorous tissue was excised.
      This syndrome was first described in 1983. The name Proteus comes from a Greek
      mythical sea god who was able to change his body form freely. This syndrome has
      numerous features including hemihypertrophy, macrodactyly, various subcutaneous
      masses, scoliosis and other minor abnormalities. Although diagnostic criteria
      have been established for Proteus syndrome, which is very difficult to
      differentiate from other congenital hamartomatous syndromes, more case reports
      are needed to define such a rare disorder. Our patient is the 6th Japanese case
      in the English literature.

PMID- 11586024
TI  - A case of subungual reactive eccrine syringofibroadenoma.
AB  - Eccrine syringofibroadenoma (ESFA) is a rare eccrine tumor. We report the case of
      a 70-year-old woman who had presented a pincer nail deformity on the toes for 55
      years and a left painless subungual tumor for 2 years. Histologic examination
      revealed branching anastomosing strands of epithelial cells with ductal
      structures in a fibrovascular stroma. The luminal cells showed positive staining
      for carcinoembryonic antigen, as in acrosyringeal cells and cells of dermal
      ducts. To our knowledge, our case is the first with a subungual location. In the
      context of chronic trauma due to a pincer nail, it may be classified in the
      reactive subtype recently described.

PMID- 11586025
TI  - Transient and partial effect of high-dose intravenous immunoglobulin in
      polyarteritis nodosa.
AB  - A 57-year-old male patient suffered from polyarteritis nodosa. He presented with
      articular pain, polyneuropathy, subcutaneous nodules and nodes on the lower legs.
      After several immunosuppressive agents (methotrexate, mycophenolate mofetil and
      prednisolone) had proven to be ineffective, 2 g intravenous immunoglobulin (IVIG)
      per kilogram body weight were administered within 2 days in combination with 10
      mg prednisolone per day. Subsequently, 6 cycles of IVIG were applied in
      increasing intervals from 4 to 6 weeks resulting in a minimum dosage of 0.33
      g/kg/week IVIG. The polyarteritis improved within a few days after the first IVIG
      application. The intensity of polyneuropathy and arthralgia of polyarteritis
      decreased during the period of IVIG treatment. Finally, a dose reduction of less
      than 0.25 g/kg/week IVIG resulted in recurring polyarteritis nodosa, which could
      not be controlled by further administration of IVIG. Therefore, our data indicate
      that: (1) IVIG is partially effective in cases of polyarteritis nodosa, but the
      therapeutic effect is only transient; (2) the success of treatment may be
      correlated with the dose of IVIG per body weight and week; (3) the efficacy/cost
      ratio of IVIG in polyarteritis nodosa appears to be low.

PMID- 11586026
TI  - Nodular scabies detected by computed dermatoscopy.

PMID- 11586027
TI  - Cutaneous bronchogenic cyst of the chin.

PMID- 11586028
TI  - Bullous pemphigoid following use of sulphasalazine for ulcerative colitis: drug
      induced eruption or true association?

PMID- 11586030
TI  - Porphyria cutanea tarda triggered by a combination of three predisposing factors.

PMID- 11586031
TI  - Nerval's diary. Le voyageur enthousiaste observe...

PMID- 11586032
TI  - Influence of preeclampsia or maternal intake of omega-3 fatty acids on the
      vasoactive effect of prostaglandin F-two-alpha in human umbilical arteries.
AB  - The vasoactive effect of prostaglandin F(2alpha) (PGF(2alpha)) was studied in in
      vitro perfused human umbilical arteries following maternal dietary
      supplementation with omega-3 fatty acids or in pregnancies complicated by a
      moderate degree of preeclampsia. In most preparations PGF(2alpha) induced a
      biphasic pressure response with a transient dilatation followed by a constrictory
      response. The pressure increase was significant in both groups, but no
      significant differences in the constrictory response or in the proportions of
      preparations displaying dilatatory responses were observed when compared to
      appropriate control groups. In conclusion, neither preeclampsia nor dietary
      supplementation with cod-liver oil had any significant effect on the vasoactive
      response to PGF(2alpha) in umbilical cord arteries.

PMID- 11586033
TI  - Transient increase in the levels of T-helper 1 cytokines in postmenopausal women
      and the effects of hormone replacement therapy.
AB  - The aim of this study was to determine, at least in part, T-cell function in
      postmenopausal women and the effects of hormone replacement therapy (HRT). Levels
      of T-helper 1 (Th1) cytokines (IL-2 and IFN-gamma) and T-helper 2 (Th2) cytokines
      (IL-4 and IL-10) produced by phytohemagglutinin-stimulated whole blood cells from
      72 untreated and 44 HRT-treated women were measured by ELISA. Thirteen of the 44
      HRT-treated women were examined before and during HRT. The production of IL-2
      increased gradually with advance of the postmenopausal period. The levels of IL-2
      in women in the early (< or =10 years) and mid (>10 and <30 years) postmenopausal
      stages were significantly higher than those in women in their second, third and
      fourth decades. The level in women in the late (> or =30 years) postmenopausal
      stage, however, was significantly lower than those in women in the early and mid
      postmenopausal stages. The level of IFN-gamma was highest in women in the mid
      postmenopausal stage. On the other hand, the levels of Th2 cytokines did not
      change with age or after menopause until the mid postmenopausal period but were
      significantly lower in women in the late postmenopausal stage. IFN-gamma levels
      in women on HRT were significantly lower than those in untreated postmenopausal
      women at all postmenopausal stages. HRT induced a significant decrease in the
      production of IL-2 and IL-4. In conclusion, production of Th1 cytokines is
      augmented in women after menopause. HRT prevents this increase, thereby improving
      the aberration of Th1/Th2 balance that is implicated in an inadequate immune
      response and pathological conditions.

PMID- 11586034
TI  - Assessing the influence of payment on motivations of women participating as
      oocyte donors.
AB  - We report on the motivations of potential ovum donors entering an assisted
      reproduction program and discuss the potential ramifications of escalating
      payments to donors. From July 1995 to July 1998, recruitment of ovum donors was
      directed at healthy women between 21 and 34 years of age. Financial remuneration
      for services rendered was USD 2,500 from July 1995 through March 1998 and
      increased to USD 5,000 after that. Donors were screened and consented according
      to established SART guidelines. The demographic background of the women was
      similar for women paid USD 2,500 to those receiving USD 5,000. The financial
      motivation was greater in those receiving USD 5,000 (68%) than USD 2,500 (39%).
      Some form of expressed altruism was similarly present in both groups (USD 5,000
      90%, and USD 2,500 91%). However, altruism expressed as the sole motivation
      occurred more in those receiving USD 2,500 (61%) compared to USD 5,000 (32%).
      Financial reimbursement has escalated for the services of ovum donors in order to
      maintain the increasing demand. While money has become a dominant factor
      motivating ovum donors, its seductive nature requires even greater attention to
      adequate informed consent. Young donors may be unable to adequately weigh the
      risks of ovarian hyperstimulation and oocyte retrieval against the monetary
      reward.

PMID- 11586035
TI  - Effect of cellular DNA content on the prognosis of epithelial ovarian cancers.
AB  - OBJECTIVE: To assess the cellular DNA status of epithelial ovarian cancers with
      regard to clinicopathological findings and its effect on prognosis. MATERIALS AND
      METHODS: Twenty-six consecutive patients with a diagnosis of epithelial ovarian
      cancer who had been treated by primary surgery and six courses of platinum-based
      chemotherapy were enrolled in this study. Second-look laparotomy (SLL) was
      performed in all cases following confirmation of the clinical remission state.
      Surgical stage, tumor grade, initial tumor volume, residual tumor volume,
      histopathologic differentiation, and SLL findings were analyzed in correlation
      with DNA ploidy and DNA index. DNA analysis was performed via DNA flow cytometry
      through paraffin-embedded tissue specimens. RESULTS: Of 26 patients, flow
      cytometric studies revealed 16 aneuploidy cases (61.5%). DNA index values ranged
      from 1.1 to 1.82 (average 1.29 +/- 0.28). The flow cytometry coefficient of
      variation mean value was set to 6.7. Taking the cutoff value of 1.2 for DNA
      indices, a fairly good correlation was detected between DNA ploidy and DNA
      indices (p < 0.001). The aneuploidy incidence was found to be high in advanced
      and poorly differentiated tumors (p < 0.05). There was statistically more
      residual tumor volume in aneuploid tumors during primary cytoreductive surgery
      and also higher recurrence rates following six courses of chemotherapy compared
      with diploid tumors (p < 0.05). No significant correlation was detected between
      the histopathologic subtypes and tumor volume (p > 0.05). Residual tumor volumes
      were larger in cases with DNA indices of 1.2 yielding higher residual tumor
      volume following surgery and being in good correlation with SLL results (p <
      0.05). The mean survival rates of cases with aneuploid tumor and a DNA index of
      >1.2 were low compared to those with diploid tumors and DNA indices of <1.2
      tumors (p < 0.05). CONCLUSION: DNA ploidy and DNA indices are important
      prognosticators for malignant epithelial ovarian tumors. They should be evaluated
      together with the patient's clinical status and other prognostic factors.

PMID- 11586036
TI  - Microsatellite instability, expression of hMSH2 and hMLH1 and HPV infection in
      cervical cancer and their clinico-pathological association.
AB  - Infection with specific genotypes of human papillomavirus (HPV) has been strongly
      implicated in cervical carcinogenesis. However, HPV infection alone is
      insufficient for malignant transformation of the cervical epithelium. An
      alteration of microsatellite repeats is the result of slippage owing to strand
      misalignment during DNA replication and is referred to as microsatellite
      instability (MSI). These defects in DNA repair pathways have been related to
      human carcinogenesis; however, the role of MSI in the tumorigenesis of cervical
      cancer remains unclear. The clinical and pathological features of cervical
      cancers which are MSI-positive have also not been fully characterized. This study
      investigated the prevalence of MSI in cervical cancer and its relationship to
      clinico-pathological characteristics and HPV infection. Polymerase chain reaction
      based microsatellite assay combined with tissue microdissection was used to
      examine for MSI in 50 cervical squamous cell carcinomas in Hong Kong women. In
      addition, the immunohistochemical staining was performed to determine the
      expression of major DNA mismatch repair genes, hMSH2 and hMLH1. Six cases (12%)
      displayed a low frequency of MSI (MSL-L) showing MSI at one locus only in 5 loci
      examined. Seven cases (14%) showed a high frequency of MSI (MSI-H) having MSI at
      2 or more loci. Grouping MSI-L and MSI-H cases together as MSI-positive,
      statistical analysis of HPV infection, tumor grade, clinical stage and clinical
      status failed to disclose differences between MSI-positive and MSI-negative cases
      (p > 0.05). However, MSI-H correlated with advanced stage of disease (p < 0.05).
      Individuals with MSI-H tumors appeared to have reduced overall survival compared
      to individuals with MSI-L and MSI-negative tumors, but the difference was not
      statistically significant (p = 0.059). An absence of either MSH2 or MLH1
      expression was observed in 2 MSI-L and 4 MSI-H cases, respectively. The results
      suggest that MSI is present in a subgroup of cervical squamous cell carcinomas,
      and defects resulting in MSI may be related to tumor progression and possibly
      poor prognosis in cervical cancer.

PMID- 11586037
TI  - Modulatory effect of acetylcholine on gonadotropin-stimulated human granulosa
      cell steroid secretion.
AB  - The aim of this study was to explore the direct action of acetylcholine on
      gonadotropin-stimulated progesterone (P) and estradiol (E(2)) secretion of human
      granulosa cells (GCs) cultured in serum-free medium. Human GCs were isolated from
      preovulatory follicular fluid aspirated from 22 women undergoing in vitro
      fertilization at the University Women's Hospital of Tubingen. The production of
      progesterone and E(2) was measured in the presence and absence of acetylcholine,
      carbachol, atropine, luteinizing hormone (LH) or follicle-stimulating hormone
      (FSH) using radioimmunoassay. Statistical analysis of the data was performed by
      ANOVA and Newman-Keuls test. Administration of acetylcholine or carbachol (10(-5)
      M) resulted in a significant increase in P and E(2) secretion. This response was
      specifically blocked by the muscarinic receptor antagonist atropine. Similarly,
      carbachol resulted in a significant increase in P and E(2) output, though the
      response to it was somewhat reduced when compared to that evoked by
      acetylcholine. Acetylcholine did not show any additive effect on LH-stimulated P
      secretion, while it augmented the stimulatory effect of FSH on P release. In
      contrast, carbachol markedly diminished the stimulatory effect of LH on P
      secretion, while it caused no change in FSH-induced P output. When administered
      together, acetylcholine did not modify the stimulatory effect of FSH on E(2)
      secretion, however, it markedly elevated LH-induced E(2) output. Similar to this,
      carbachol significantly increased LH-induced E(2) release, however it decreased
      FSH-stimulated E(2) secretion. We suggest that acetylcholine has a direct
      modulatory effect on gonadotropin-stimulated steroid production of GCs, an effect
      that is mediated via muscarinic receptors. This effect may have a physiological
      role in the regulation of GC function during the menstrual cycle.

PMID- 11586039
TI  - Clinical and epidemiological features of syphilis in pregnant women: the course
      and outcome of pregnancy.
AB  - Clinical and epidemiological features of syphilis and the course and outcome of
      pregnancy were studied in 155 pregnant women infected with syphilis; 95 (61%)
      women were unemployed, 47% were unmarried. Syphilis proceeded without clinical
      manifestations in 121 cases (78%). Discordant results of complement fixation
      (Wassermann) test, precipitation test, Treponema pallidum immobilization test,
      and fluorescent antibody test were observed in 22 (14%) of the women. Pregnancy
      pathology was observed in 75 cases (48.8%) and more often appeared as anemia in
      49 (31.5%), stillborn in 46 (29.8%) and toxicosis in 44 (28.4%). Fetal ultrasonic
      stigmas of infection were evident in 23 cases (49%). There was distension of the
      brain ventricle system and hepatomegaly each in 1 case (2%), transvascular
      infiltration of liver in 2 cases (4%), dilation of intestinal loops,
      gastromegaly, ventriculomegaly and petrifaction in lungs each in 1 case;
      ultrasonic changes in vessels of organs: of the liver in 4 cases (8%), intestines
      and stomach in 16 cases (32%), lungs in 4 cases (8%), kidneys in 10 cases (21%)
      and of the ventricular system in 9 cases (19%). Fetus development retardation was
      revealed in 3 cases (6%), fetal hypoxia in 1 (2%), hypohydrosis in 2 (4%) and
      hydropsy in 1 case (2%). The pregnancy pathology in women with syphilis was
      considered not pathognomonic.

PMID- 11586038
TI  - Effect of gonadotropin-releasing hormone agonist treatment upon angiogenesis in
      uterine leiomyoma.
AB  - OBJECTIVE: To assess the effect of gonadotropin-releasing hormone (GnRH) agonist
      treatment upon angiogenesis in uterine leiomyomata. METHODS: Uterine leiomyomata
      specimens of 49 consecutive patients who underwent myomectomy or hysterectomy
      following presurgical treatment with (n = 23) and without (n = 26) GnRH agonist
      were stained immunohistochemically with antibody to factor VIII-related antigen.
      For each subject, age, parity, number of Lupron treatments, leiomyoma size (cm),
      and mean microvessel counts calculated from three fields (x400) were recorded.
      Differences in patient age, parity, microvessel counts and leiomyoma size between
      GnRH agonist treated and untreated patients were tested by unpaired Student's t
      test. Differences among the various number of doses were tested by one-way ANOVA,
      with Bonferonni and Neuman-Keuls post hoc tests between specific dose-number
      groups. The relationship between microvessel counts and leiomyoma size was tested
      by Pearson correlation test. Multivariate stepwise regression tested the
      relationship between the number of Lupron doses and microvessel counts,
      correcting for age, parity, and leiomyoma size. p < 0.05 was considered
      significant. RESULTS: Patient age and parity were similar in GnRH treated and
      untreated patients (mean 43.3 +/- 6.6 versus 43.9 +/- 7.5 years and median 2
      (range 0-7) versus 1 (range 0-5), p = 0.78 and p = 0.45, respectively).
      Microvessel counts of leiomyomata specimens treated presurgically with GnRH
      agonist therapy (median 22.7, range 6.7-65.7) were not significantly different
      from microvessel counts of specimens without presurgical GnRH agonist treatment
      (median 19.8, range 6-53; p = 0.77). No correlation between leiomyoma size and
      microvessel counts was noted (r = 0.06, P = 0.7). CONCLUSION: Angiogenesis as
      assessed by microvessel counts in surgically removed leiomyomata is not affected
      by presurgical medical management with GnRH agonist therapy.

PMID- 11586041
TI  - Lack of an association of a single nucleotide polymorphism in the promoter of the
      matrix metalloproteinase-1 gene in Czech women with pregnancy-induced
      hypertension.
AB  - In preeclampsia the cytotrophoblast invasion of the decidual vessels is reduced.
      The endothelia in the decidual vessels may influence cytotrophoblast invasion and
      remodeling of decidual spiral arteries. The decidual endothelial cells from
      preeclamptic placentas produce less matrix metalloproteinase-1 (MMP1) than those
      from normal placentas. MMPs form a group of enzymes that are capable of degrading
      components of extracellular matrix. The present study investigated the prevalence
      and possible association of an insertion of guanine in the promoter of the MMP1
      gene in pregnancy-induced hypertension, preeclampsia and eclampsia in the Czech
      population. This was a case-control study. No differences were observed in
      genotype frequencies between cases and controls. The insertion of the guanine in
      the promoter of the MMP1 gene does not appear to increase the risk of development
      of pregnancy-induced hypertension, preeclampsia and eclampsia.

PMID- 11586040
TI  - The importance of the removal of the intrauterine device in genital colonization
      by actinomyces.
AB  - OBJECTIVE: To determine whether, in addition to treatment with antibiotics, it is
      necessary to remove the intrauterine device (IUD) to eliminate genital
      colonization by Actinomyces. METHODS: A randomized clinical trial was carried
      out. Patients were divided into two groups. The intervention group did not have
      their IUDs removed, while the control group did. Both groups were treated with
      trimethoprim and sulfamethoxazole. A total of 43 patients were included. RESULTS:
      The patients from the intervention group and the control group proved to be
      comparable. The post-intervention cytology smear tested negative for Actinomyces
      in 100% of the patients whose IUD had been removed and in 66.7% of those whose
      IUD had not been removed (p = 0.005). The probability that colonization by
      Actinomyces will continue if the IUD is not removed is greater the longer the
      patient has been exposed to the IUD. After 24 months, relative risk (RR) = 2,
      after 36 months RR = 2.16 and after 48 months RR = 2.66. CONCLUSIONS: The removal
      of the IUD has been effective in genital colonization by Actinomyces. The
      protective effect exerted by the removal of the IUD was found to be greater in
      proportion to the length of time the patient had used it.

PMID- 11586042
TI  - Maternal arrhythmias of normal labor and delivery.
AB  - Labor and delivery are associated with significant hemodynamic changes, as well
      as pain and anxiety, all of which could be fertile ground for arrhythmias. In
      order to establish whether cardiac arrhythmias occur more frequently during labor
      and delivery in healthy parturients and whether it clinically affects the mother
      or the newborn, 100 pregnant women admitted for delivery had Holter monitoring
      before, during, and up to 1 h postpartum. Our results show that, excluding sinus
      rhythm variations, only a slight majority of the study subjects had arrhythmia at
      all, while only 2% had more complex arrhythmias, none of which required any
      therapeutic intervention. We conclude that cardiac arrhythmias occurring during
      labor, delivery, and postpartum in the healthy parturient are no more frequent
      than in the general female population of the same age and are without clinical
      consequences for the mother and the newborn.

PMID- 11586043
TI  - Expression of ovarian prolactin receptor in relation to hormonal changes during
      induction of ovulation in the rat.
AB  - We examined the relationships between the expression of the short and long forms
      of the prolactin (PRL) receptor (PRLR) mRNA in the ovary and changes in the
      levels of serum hormones such as sex steroid hormones and PRL during induction of
      ovulation in the rat. The expression of both forms of PRLR mRNA in the ovary was
      examined by Northern blot analysis in immature female rats treated with pregnant
      mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Ovarian
      tissues and blood samples were obtained before treatment, 24 and 48 h after PMSG
      injection and 4, 6, 8, 12, 24 and 48 h after hCG treatment. Serum levels of
      17beta-estradiol, progesterone and PRL were determined by radioimmunoassay. Serum
      levels of 17beta-estradiol rapidly increased to a maximal level 48 h after PMSG
      injection and then rapidly declined until 4 h after hCG injection. Serum levels
      of progesterone gradually increased after PMSG treatment, markedly increased to
      114.2 nmol/l 8 h after hCG treatment and remained high until 48 h after hCG
      treatment. The serum level of PRL peaked at 66.2 microg/l (p < 0.01) 48 h after
      PMSG injection, and a temporary decrease after hCG treatment was followed by a
      continuously high level from 8 to 48 h. The expression of the long form of PRLR
      mRNA increased significantly (p < 0.01) to 688% of the control level after PMSG
      treatment, while that of the short form increased to only 184% of the control
      level. The expression of the long form of PRLR-mRNA rapidly declined until 6 h
      and then gradually increased until 48 h after hCG treatment. On the other hand,
      the expression of the short form of PRLR mRNA decreased to a nadir 12 h after hCG
      injection and then increased significantly (p < 0.01) to 142% of the control
      level. Our results showed that the changes in the short and long forms of PRLR
      mRNA differed in a time-specific manner and that these two forms are involved in
      different functions in the rat ovary during induction of ovulation. It is thought
      that the long form of PRLR mRNA is involved in folliculogenesis, while the short
      form of PRLR mRNA may play an important role in the formation and maintenance of
      the corpus luteum in the rat ovulatory cycle.

PMID- 11586044
TI  - Resistance to multiple agent chemotherapy including cisplatin after chronic low
      dose oral etoposide administration in gestational choriocarcinoma.
AB  - Most patients with gestational trophoblastic disease in whom single-agent or even
      combination chemotherapy has failed can be cured with salvage chemotherapy
      including etoposide or platinum-based regimens. Here we report a rare case of
      uterine choriocarcinoma following a molar evacuation that seemed to develop
      during chronic low-dose oral administration of etoposide for approximately 16
      months. Although the patient was expected to have a good chance of cure using
      combination chemotherapy, the lesion was resistant to multiple-agent chemotherapy
      including cisplatin.

PMID- 11586045
TI  - Treatment of fetal congenital complete heart block with maternal administration
      of beta-sympathomimetics (terbutaline): a case report.
AB  - We report a case of fetal congenital heart block treated with maternal
      administration of beta-sympathomimetics. The case was diagnosed as fetal complete
      heart block associated with maternal anti-Ro/SS-A antibody at 22 weeks of
      gestation. By fetal sonography, the ventricular rate was revealed to be 60
      beats/min and mild cardiomegaly was shown. We initiated maternal administration
      of a sympathomimetic, specifically terbutaline, to prevent fetal heart failure.
      An increase in the fetal ventricular rate and an improvement in cardiac function
      were both achieved during the treatment. A viable infant was delivered by an
      elective cesarean section without complications at term. Maternal administration
      of the beta-adrenergic agent terbutaline is suggested to be effective for
      improving fetal congenital heart block in order to prevent heart failure in
      utero.

PMID- 11586046
TI  - Paraneoplastic cerebellar degeneration: neurological symptoms pointing to occult
      ovarian cancer.
AB  - Paraneoplastic cerebellar degeneration with anti-Yo antibodies is a rare but
      disabling neurodegenerative disease that may point to an occult ovarian cancer.
      Symptoms usually accompanying paraneoplastic cerebellar degeneration include
      truncal and limb ataxia, dysarthria, dysphagia, nystagmus, vertigo, and diplopia.
      The pathogenesis of paraneoplastic neurological syndromes is unknown. Treatment
      results of the neurological symptoms are disappointing. The present case
      illustrates how neurological symptoms pointed to an occult ovarian cancer.

PMID- 11586047
TI  - [XVII Academic Meeting of German-speaking University Teachers of Gynaecology and
      Obstetrics. Salzburg, October 3-5, 2001. Abstracts].

PMID- 11586048
TI  - Morning and evening plasma melatonin and dexamethasone suppression test in
      patients with nonseasonal major depressive disorder from northern Greece
      (latitude 40-41.5 degrees ).
AB  - INTRODUCTION: The present study aimed to search for correlations between
      melatonin (MT) levels and the dexamethasone suppression test (DST) and clinical
      variables. METHODS: Fifty depressed patients aged 21-60 years took part in the
      study. The Schedules for Clinical Assessment in Neuropsychiatry, version 2.0, and
      the International Personality Disorders Examination were used for diagnosis.
      Psychometric assessment included the Hamilton Depression Rating Scale, the
      Hamilton Anxiety Scale, the General Assessment of Funtioning Scale, the Newcastle
      scales and the Diagnostic Melancholia Scale. The DST and 9.00 and 23.00 h MT
      values were assessed. Statistical analysis included Student's t test, Pearson
      product moment correlation coefficient and forward stepwise multiple linear
      regression analysis. RESULTS: Melancholic patients had lower 23.00 h MT values in
      comparison to the rest of the patients and the atypical and 'undifferentiated'
      patients. CONCLUSION: The current study shows that low MT values were closely
      related to melancholic depression. Distinct quality of mood, psychomotor
      agitation or retardation and anorexia or weight loss seemed to be responsible for
      this relationship.

PMID- 11586049
TI  - Association analysis of a functional G protein beta3 subunit gene polymorphism
      (C825T) in mood disorders.
AB  - The guanine nucleotide-binding proteins (G proteins), heterotrimers consisting of
      alpha, beta and gamma subunits, convey signals initiated by the activation of
      many neurotransmitter receptors. Evidence for involvement of the G proteins in
      mood disorders relies on the effects of mood stabilizers and antidepressants on G
      protein function. In addition, abnormalities in the expression of G proteins have
      been demonstrated in mood disorder patients. Therefore, we tested the hypothesis
      that a functional polymorphism (C825T) in the G protein beta3 gene subunit (GNB3)
      confers susceptibility to mood disorders. A population-based association study
      was utilized, and GNB3 was genotyped for 144 mood disorder patients and 153
      normal controls. The results reveal that it is not likely that the C825T
      polymorphism in the GNB3 gene subunit is involved in mood disorder pathogenesis.
      Further studies of the associations between other G protein subunits and mood
      disorder are needed to fully elaborate the involvement of this protein in mood
      disorders.

PMID- 11586050
TI  - Correlation between platelet alpha(2)-adrenoreceptors and symptom severity in
      major depression.
AB  - BACKGROUND: Abnormalities in different parameters of the norepinephrine system
      have been widely described in major depression. The presence of alpha(2)
      adrenoreceptors in blood platelets, similar to those in the brain, prompted us to
      evaluate them in depressed patients, as compared with healthy controls. METHODS:
      Fifteen outpatients affected by major depression, according to DSM IV criteria,
      and 15 comparable healthy control subjects, were included in the study. The
      alpha(2)-adrenoreceptors were measured by means of the specific binding of
      [(3)H]rauwolscine, a highly selective antagonist for this receptor subtype. The
      severity of depression was assessed by means of the Hamilton Rating Scale for
      Depression (HRSD). RESULTS: The results did not show any difference in
      [(3)H]rauwolscine binding parameters (B(max) and K(d)) between patients and
      controls. However, in the patients, a significant and positive correlation
      between B(max), which measures the density of the receptors, and HRSD total score
      was detected. CONCLUSIONS: Therefore, although no change in alpha(2)
      adrenoreceptors seems to occur in major depression, the density of these
      receptors would seem to be related to the severity of depressive symptoms.

PMID- 11586051
TI  - Analysis of the metabolism of haloperidol and its neurotoxic pyridinium
      metabolite in patients with drug-induced parkinsonism.
AB  - The blood levels of the neurotrophic drug haloperidol (HP) and its pyridinium
      metabolite, HPP(+), have been analyzed by liquid chromatography/electrospray
      ionization-mass spectrometry in 10 schizophrenic patients treated with HP,
      without carbamazepine (HP, oral daily dose of 0.3-0.5 mg/kg body weight for more
      than 1 year, females, aged 41 +/- 8.5 years). There was a significant difference
      (t-test, d.f. = 8, p (t(0) = 7.2) <0.005) in the blood HPP(+) level between the 5
      patients with (18.5 +/- 6.4 ng/ml) and the 5 without (6.3 +/- 2.4 ng/ml) severe
      side effects such as drug-induced parkinsonism (Extrapyramidal Symptom Rating
      Scale (ESRS) parkinsonism severity scores 2.8 +/- 1.5 and 1.8 +/- 1.1,
      respectively). Moreover, it is suggested that vitamin E may be effective for drug
      induced parkinsonism through a change in the blood HPP(+) level. It is necessary
      to investigate the HPP(+) metabolism in psychiatric patients to avoid severe side
      effects such as drug-induced parkinsonism and cardiac functional disorders.

PMID- 11586052
TI  - Possible relationship between combined plasma concentrations of risperidone plus
      9-hydroxyrisperidone and extrapyramidal symptoms. Preliminary study.
AB  - We investigated the relationships between extrapyramidal symptoms (EPS) induced
      by risperidone, the dosage of risperidone and the combined plasma concentrations
      of risperidone plus its active metabolite, 9-hydroxyrisperidone, in 20
      schizophrenic patients. There was a positive correlation between the scores on
      the Simpson and Angus Scale and both the dosage of risperidone and the sum of the
      plasma levels of risperidone and 9-hydroxyrisperidone. These results suggest that
      EPS induced by risperidone increase in conjunction with both the dosage of
      risperidone and the total plasma concentrations of the parent compound and its
      active metabolite.

PMID- 11586053
TI  - Predictive value of amino acids in the treatment of major depression with
      fluvoxamine.
AB  - Sixteen outpatients (mean age +/- SD 50.18 +/- 11.55 years; 11 females and 5
      males) affected by major depression without melancholia (DSM-IV) were included in
      the study. The control group consisted of 11 healthy volunteers (mean age +/- SD
      39.90 +/- 13.39 years; 2 females and 9 males). Patients were treated with
      fluvoxamine (FVX) 100-300 mg daily. Clinical assessment was performed using the
      Hamilton Rating Scales for Anxiety and Depression (HRS-A; HRS-D) and the Clinical
      Global Impression Scale (CGI) at basal time (T(0)), after 4 weeks and after 8
      weeks (T(8)). Plasma and platelet amino acid levels were determined at T(0) in
      all the subjects and also at T(8) in depressed patients. A significant clinical
      improvement was observed in depressed patients according to the HRS-A (p =
      0.004), HRS-D (p = 0.008) and CGI (p = 0.002). A negative correlation (r = -0.53,
      p = 0.049) was found between platelet levels of valine and HRS-D improvement
      rate. Patients showed significantly higher tyrosine/large neutral amino acids
      (LNAAs) and lower tryptophan/LNAAs, ratios which could represent an index of good
      response to a serotonergic drug like FVX.

PMID- 11586054
TI  - Insomnia related to dysthymia: polysomnographic and psychometric comparison with
      normal controls and acute therapeutic trials with trazodone.
AB  - Utilizing polysomnography (PSG) and psychometry, objective and subjective sleep
      and awakening quality was investigated in 11 patients (mean age 50 +/- 14) with
      nonorganic insomnia (F 51.0) related to dysthymia (F 34.1) as compared with 11
      age- and sex-matched normal controls. Patients demonstrated decreased sleep
      efficiency and sleep stage S2 as well as increased sleep latency to S1, S2 and
      S3, wakefulness within the total sleep period, number of awakenings, S1 and REM
      sleep. There was no intergroup difference in REM latency. Subjective sleep
      quality and the total score of the Self-Assessment Scale for Sleep and Awakening
      Quality (SSA) were deteriorated as were evening and morning well-being, mood,
      affectivity and drowsiness. Noopsychic measures showed deteriorated numerical
      memory, fine motor activity and reaction time variability. In a placebo
      controlled crossover design study, the acute effects of 100 mg trazodone, a
      serotonin reuptake inhibitor with a sedative action due to 5HT(2) and alpha(1)
      receptor blockade, were investigated in the patients. As compared with placebo,
      trazodone induced an increase in slow-wave sleep (S3 + 4), a lengthening of REM
      latency, a decrease in REM sleep and a normalization of the periodic leg movement
      (PLM) index. In the morning, there was a minimal increase in somatic complaints
      and a decrease in critical flicker frequency and systolic blood pressure. In
      conclusion, our study demonstrated that dysthymia induced significant changes in
      objective and subjective sleep and awakening quality, which were counteracted by
      100 mg trazodone, thus suggesting a key-lock principle in the treatment of
      nonorganic insomnia related to dysthymia with this drug.

PMID- 11586055
TI  - Effects of strain, behavior and age on the self-administration of ethanol,
      nicotine, cocaine and morphine by two rat strains.
AB  - Two genetically different strains, Brown Norway rats (BNR) and Wistar Kyoto rats
      (WKR), with the latter showing higher emotionality and lower plasma stress
      catecholamine responses, were compared for their voluntary intake of ethanol,
      nicotine, cocaine and morphine. Younger BNR self-administered the same amounts of
      all 4 substances as did the younger WKR suggesting a similar genetic basis for
      all drugs at this age. Older BNR consumed less ethanol and nicotine but equal
      amounts of cocaine and morphine as compared to older WKR, and older BNR were more
      sensitive to the effects of ethanol than WKR suggesting a different genetic basis
      for different drugs at an older age. Forcing both strains to consume one of the
      drugs did not affect a subsequent voluntary consumption of ethanol and morphine
      but reduced nicotine intake in WKR and decreased cocaine intake in both strains
      suggesting that drug use is determined by individual preferences and not drug
      exposure per se. The behavioral characteristics of both strains coincide only
      with the self-administration of ethanol and nicotine supporting a possible
      genetic linkage between anxiety/stress and ethanol and nicotine use.

PMID- 11586057
TI  - Aqueous humor and serum tumor necrosis factor-alpha in clinical uveitis.
AB  - OBJECTIVE: To study the local and systemic behavior of the tumor necrosis factor
      alpha (TNF-alpha) in patients with active uveitis. METHODS: TNF-alpha levels were
      measured in aqueous humor and peripheral blood samples using an enzyme-linked
      immunosorbent assay from 23 patients with uveitis and 16 control patients who had
      been operated on for uncomplicated cataracts. RESULTS: Aqueous humor and sera of
      patients with uveitis showed higher levels of TNF-alpha than those of controls (p
      < 0.001). A comparison of cytokine levels between aqueous humor and sera showed
      significantly higher levels of TNF-alpha in serum than aqueous humor (p < 0.001).
      Correlation studies using the regression test for successive steps showed that
      serum TNF-alpha levels correlated with recurrent uveitis (r = 0.4150; p =
      0.0489). CONCLUSIONS: TNF-alpha is a cytokine that participates actively in the
      pathogenesis of clinical uveitis. Our data emphasize the greater systemic than
      local participation of TNF-alpha. Finally, an elevated serum TNF-alpha seems to
      be associated with a recurrent pattern of uveitis.

PMID- 11586056
TI  - Glucose and glucoregulatory modulation of memory scanning, event-related
      potentials and EEG in elderly subjects.
AB  - Endogenous P300b event-related potential (ERP) and behavioral performance
      measures, extracted during a visual memory scanning task, and spectral indices of
      resting electroencephalographic (EEG) activity, were assessed in 12 healthy
      elderly adults before and after double-blind oral administration of a placebo or
      glucose (50 mg) beverage. Glucoregulation was estimated by deriving a recovery
      index to categorize subjects as having better (BR) or poorer (PR) blood glucose
      recovery. Although glucoregulatory status did not impact on EEG or task
      performance, PR subjects exhibited reduced P300b areas relative to BR subjects
      prior to beverage administration. Glucose did not alter P300b or memory scanning
      performance but, regardless of glucoregulatory status, it increased the EEG power
      in the slow alpha frequency band. The study results suggest that peripheral
      glucoregulation can influence neuroelectric measures of cognition and that the
      acute ingestion of glucose can modulate central arousal processes.

PMID- 11586058
TI  - Thalidomide inhibits leukocyte-endothelium interaction in endotoxin-induced
      uveitis.
AB  - To investigate the effects of thalidomide on leukocyte-endothelium interaction in
      iris vessels of rats with an endotoxin-induced uveitis (EIU), intravital
      fluorescence microscopy was used to quantify leukocyte adhesion to the vascular
      endothelium of iris venules in Lewis rats at 2, 4, 8 and 24 h after induction of
      EIU. Animals (n = 84) received a single intraperitoneal dose of either
      thalidomide (80 mg/kg body weight) or prednisolone (10 mg/kg body weight). Both
      drugs significantly reduced firm adhesion of leukocytes at 4, 8 and 24 h.
      Thalidomide caused earlier suppression of leukocyte rolling than prednisolone (4
      vs. 8 h). TNF-alpha plasma levels peaked at 2 h and were not significantly
      reduced in any group compared with controls. Cell count and protein concentration
      in aqueous humor were significantly reduced by prednisolone and thalidomide at 24
      h (p < 0.05). Thalidomide exerts its anti-inflammatory effects by an inhibition
      of leukocyte-endothelium interaction. Compared with prednisolone, thalidomide
      shows earlier inhibition of leukocyte rolling, indicating modulation of adhesion
      molecule expression and/or function.

PMID- 11586059
TI  - Light scattering in normal and cataractous lenses of farmed Atlantic salmon
      (Salmo salar): a slit lamp and Scheimpflug photographic study.
AB  - To investigate normal light scattering and cataract formation, the anterior eye
      segments of farmed Atlantic salmon (Salmo salar) reared in fresh water and sea
      water were documented in vivo for the first time with a Topcon SL-45 Scheimpflug
      camera. A total of 40 fish from the fresh-water-rearing period, obtained from 2
      groups of identical age but showing a different growth rate, and 24 fish from the
      sea-water-rearing period, sampled from 2 groups with identical age but being fed
      different food brands, were included in this study. The fish were anaesthetized
      before examination. Due to the naturally wide pupil, no mydriatic compound was
      applied. All fish were removed from the water for photography, which was
      performed for each eye in 0 degrees = vertical slit position. Images were
      recorded on Kodak Tmax 400 black-and-white film. Microdensitometric image
      analysis of all negatives was performed using a Joyce-Loebl online
      microdensitometer. In spite of the virtual absence of an anterior chamber gap
      between cornea and lens and very little light scattering in the normal fish lens,
      a small number of distinct layers could be reproducibly identified in the lens.
      While there was little abnormal light scattering which could point to cataract
      development in young fish from the fresh water period, the evaluation of the
      lenses from the 2 sea water groups showed the presence of specific forms of
      cataract especially in the cortical and supranuclear layers. There were
      significant differences between the groups fed different food brands at the sea
      water site. In conclusion, Scheimpflug photography proved to be applicable to eye
      research in fish in vivo. It is suggested that this method should be employed for
      reproducible documentation as an extension to slit lamp monitoring in
      experimental research to reveal causative factors for cataracts in farmed fish.

PMID- 11586060
TI  - Effect of pneumatic suction ring placement on intraocular pressure in cats.
AB  - PURPOSE: To determine the effect of placing a pneumatic suction ring on
      intraocular pressure (IOP) in the cat and to design an improved method to
      generate a stable elevation of IOP. METHODS: A pneumatic suction ring was applied
      to the eye in cats while the IOP was monitored. Three groups of animals (10 per
      group) were used. A vacuum pressure of 450 mbar was applied in one step to eyes
      of group 1 (anesthetized) and to group 2 (euthanized) cats. In group 3
      (anesthetized) cats, an initial vacuum pressure of 250 mbar was applied, followed
      by a vacuum of slowly increasing pressure at a rate of 5 mbar/min for a total of
      40 min to 450 mbar. RESULTS: After the one-step application of a vacuum (450
      mbar) to the eyes of anesthetized cats (group 1), IOP peaked within the first
      minute from a basal value of 25 +/- 2 mm Hg (mean +/- SD) to 90 +/- 7 mm Hg. It
      then rapidly decreased to 69 +/- 2 mm Hg 5 min later and continued to decrease to
      39 +/- 4 mm Hg 40 min later. This sharp peak and decline of IOP were also
      observed in eyes of euthanized cats (group 2). The basal IOP of these eyes was 8
      +/- 1 mm Hg. It rose to 18 +/- 2 mm Hg immediately after the application of
      vacuum pressure (450 mbar) and returned to the basal level 5 min later. In
      contrast, the eyes of group 3 receiving an initial vacuum of 250 mbar followed by
      a 5 mbar/min vacuum increment exhibited a rapid increase in IOP and a very stable
      plateau (mean IOP = 62-68 mm Hg), lasting the whole study period (40 min).
      CONCLUSION: IOP after a one-step application of a vacuum via a pneumatic suction
      ring is self-adjusting and declines rapidly over time. This decline in IOP can be
      overcome by a supplementary increment in vacuum pressure.

PMID- 11586061
TI  - Functional magnetic resonance imaging of eye dominance at 4 tesla.
AB  - We studied eye dominance in visual cortex and lateral geniculate nucleus (LGN)
      using functional magnetic resonance imaging (fMRI) at a very high magnetic field
      (4 tesla). Eight normal volunteers were studied with fMRI at 4 tesla during
      alternating monocular visual stimulation. The acquisition was repeated twice in 4
      subjects to confirm reproducibility. In addition, magnetic resonance signal
      intensities during three conditions (right eye stimulation, left eye stimulation,
      and control condition) were compared to determine whether the observed area was
      truly or relatively monocular in 2 subjects. In both the individual and group
      analyses, the anterior striate cortex was consistently activated by the
      contralateral eye more than the ipsilateral eye. Additionally, we found evidence
      that there were areas in the bilateral LGN which were more active during the
      stimulation of the contralateral eye than during the stimulation of the
      ipsilateral eye. The activated areas were reproducible, and the mean ratio of the
      overlapping area was 0.71 for the repeated scans. The additional experiment
      revealed that the area in the anterior visual cortex could be divided into two
      parts, one truly monocular and the other relatively monocular. Our finding
      confirmed previous fMRI results at 1.5 tesla showing that eye dominance was
      observed in the contralateral anterior visual cortex. However, the eye dominance
      in the visual cortex was found not only in the most anterior area corresponding
      to the monocular temporal crescent but also in the more posterior area,
      presumably showing the greater sensitivity of the temporal visual field (nasal
      retina) as compared with the nasal visual field (temporal retina) in the
      peripheral visual field (peripheral retina). In addition, it is suggested that
      the nasotemporal asymmetry of the retina and the visual fields is represented in
      the LGN as well as in the visual cortex.

PMID- 11586062
TI  - Role of thyroid hormone in craniofacial and eye development using a rat model.
AB  - Thyroid hormones (TH) are essential for somatic and neural development.
      Epidemiological studies have pointed to TH-dependent craniofacial features
      occurring during development. In an attempt to elucidate the precise role of TH
      in the developing eyes and adnexa (orbit, lids, nasolacrimal structures), we
      analysed the craniofacial and eyeball developmental characteristics in a rat
      model of congenital-neonatal hypothyroidism (HG), induced by combined chemical
      surgical thyroidectomy. The heads and eyeballs from control and HG animals were
      obtained at key developmental stages and processed for scanning electron, light
      and transmission electron microscopy. On embryological day 13 (E13),
      significantly reduced values for head parameters (25% less), optic primordia area
      (0.053 +/- 0.0085 vs. 0.111 +/- 0.012 microm(2); p < 0.05) and volume (3.96 +/-
      0.141 vs. 8.09 +/- 0.123 microm(3); p < 0.05) were found in the HG with respect
      to the controls. In addition, a delayed prenatal eye closure and postnatal eye
      opening took place in the treated rats. The photoreceptor and ganglion cell layer
      thickness displayed significantly lower values (p < 0.001) in HG, at each
      developmental time point. Postnatally, a delay in photoreceptor outer segment
      morphogenesis (in relation to retarded disc formation) and significantly lower
      values for ganglion cell nuclear volumes (p < 0.001) and nuclear pore density (p
      < 0.01) were observed in the TH-deficient animals. All data suggest that TH play
      a pivotal role in the development of the face and eye. Therefore, a series of
      defects due to a loss of TH actions involved in anterior-posterior development of
      the head and face and the loss of TH-dependent signals crucial for cell
      differentiation, migration, proliferation and establishment of definitive cell
      phenotypes in the eyes may appear. Gestational and neonatal screenings for
      thyroid functioning are suggested to paediatricians and ophthalmologists in order
      to prevent craniofacial malformations and visual abnormalities.

PMID- 11586063
TI  - Gene transfer by adenovirus in rabbit iris sphincter muscle.
AB  - The effect of insertion of an exogenous gene on smooth muscle function in rabbit
      iris sphincter muscle was investigated. An adenoviral vector encoding the
      bacterial LacZ gene (AdLacZ, 10(7) pfu) and viscoelastics were injected into the
      posterior chamber of eyes of albino rabbits. Three days after injection, the
      effects of acetylcholine (Ach), carbachol (Carb), substance P (SP) and electrical
      field stimuli on isolated iris sphincter were investigated using isometric
      tension-recording methods. X-Gal histostaining showed that iris sphincter smooth
      muscle cells were transfected in 7 of 11 muscle strips. Contraction-response
      curves for Ach, Carb or SP were not different from control. We conclude that the
      iris sphincter muscle can be gene-transfected by posterior chamber infusion of an
      adenoviral vector with viscoelastics. Adenovirus-mediated gene transfer per se
      had no measurable effect on tension development.

PMID- 11586064
TI  - Heat shock protein 70 expression increased in rabbit muller cells in the ischemia
      reperfusion model.
AB  - Heat shock protein 70 (HSP70) expression in the rabbit retina was evaluated in
      the ischemia-reperfusion model. Ischemia was induced by increasing the pressure
      in the anterior chamber, and the retinas were collected 1 or 12 h after
      reperfusion. HSP70 expression was examined by Western blot, confocal laser
      scanning microscopy and immunoelectron microscopy. Western blot showed that HSP70
      was significantly increased in the retina 12 h after reperfusion, compared with
      normal control or 1 h after reperfusion. Confocal microscopy demonstrated that
      HSP70 was constitutive in Muller cells and that its expression was increased 12 h
      after reperfusion. Electron microscopy showed that glycogen-like granules were
      significantly decreased with prominent endoplasmic reticulum 1 h after
      reperfusion. Twelve hours after reperfusion, however, the density of glycogen
      like granules was restored, and immunoelectron microscopy indicated that HSP70
      was associated with the organelles of the Muller cells. Taken together, these
      data suggest that HSP70 in Muller cells plays a role in accommodation to stress.

PMID- 11586066
TI  - Perforin granule release from cytotoxic lymphocytes ex vivo is inhibited by
      ciclosporin but not by methotrexate.
AB  - The 70-kD plasma membrane pore-forming protein perforin is a key component of
      lymphocyte cytotoxicity mediated by lytic granules. It represents a major player
      in the regulation of various immune reactions like immunoglobulin synthesis, T
      cell activation and homeostasis, and in the elimination of virus-infected and
      tumor cells. Dysregulation of the perforin-granule system, i.e. an increase of
      perforin-containing lymphocytes, was recently demonstrated in exacerbated
      psoriasis and generalized drug reactions. In contrast, in patients with
      exacerbated atopic dermatitis or unsymptomatic rhinitis allergica, a severe
      perforin depletion in cytotoxic T cells was demonstrated. In addition, these
      cells displayed a remarkable transport defect of lytic granules, i.e. a perforin
      hyperreleasability. Thus, the process of perforin-granule release may represent
      an attractive target for therapeutic immune modulation in various dermatological
      diseases. Ficoll isolated peripheral blood mononuclear cells (PBMCs) of healthy
      volunteers were preincubated with different concentrations of ciclosporin or
      methotrexate (MTX) for 1 h. A newly developed flow cytometry based perforin
      release assay was used to quantify the velocity of ionomycin/phorbol 12-myristate
      13-acetate stimulated perforin-granule release in the presence or absence of
      pharmacological agents. The immunosuppressant MTX did not influence perforin
      granule release. Ciclosporin, in contrast, was found to inhibit perforin-granule
      release significantly and dose dependently: whereas release from CD8(+)
      lymphocytes was almost maximal for the untreated control after 60 min (41% of
      CD8(+) perforin(+) cells at time zero), ciclosporin at 20, 4 and 2 microg/ml
      elevated the aforementioned parameter up to 73, 65 and 53%, respectively. Our
      data demonstrate that (i) perforin-granule release can be targeted efficiently by
      pharmacological agents which can be monitored directly in a newly developed
      perforin-granule release assay, and (ii) suppression of perforin-granule based
      cytotoxicity by ciclosporin might contribute to the beneficial therapeutic
      effects of this drug as an immunomodulating and immunosuppressant target.

PMID- 11586067
TI  - Sphingolipid signaling in epidermal homeostasis. Current knowledge and new
      therapeutic approaches in dermatology.
AB  - In the present review we have attempted to give an overview of the role of
      sphingolipids in skin homoeostasis. Sphingolipid metabolites are emerging as
      potent second messengers in diverse cellular signaling pathways. In the skin
      little is known about sphingolipids in signaling events. In various cell
      populations it has been shown that different sphingolipid metabolites have
      opposing effects on the biological outcome of a stimulus. Therefore, the term
      'sphingolipid rheostat' has been established and has also been shown to exist in
      skin-derived cell populations. In many cells ceramide is a mediator of
      proliferation inhibition and apoptosis, whereas sphingosine-1-phosphate acts more
      like a growth factor and reverses ceramide effects. In keratinocytes
      extracellular and intracellular ceramides play important roles. Extracellular
      ceramides are necessary for the water retention capacity and for maintaining the
      permeability barrier of the skin. Intracellular ceramides cause differentiation
      of keratinocytes. Until now less is known about the effect of other sphingolipid
      metabolites in the skin.

PMID- 11586068
TI  - Alternatively activated antigen-presenting cells: molecular repertoire, immune
      regulation, and healing.
AB  - The Th1/Th2 paradigm has stimulated extensive research into the mechanisms
      underlying T-cell polarization; alternative activation of antigen-presenting
      cells (APCs) has turned out to be the corresponding concept APC polarization.
      Macrophages (M phi) as well as dendritic cells (DCs) can undergo Th1- or Th2-like
      polarization; APC1 and APC2 thus acquire the capacity to drive the development of
      naive T cells and the reactivation of resting T cells towards either a Th1 or a
      Th2 phenotype, respectively. Among polarized APC, effector macrophages are
      classically activated by mediators such as IFN-gamma, TNF-alpha or LPS (M phi 1),
      while M phi 2 are alternatively activated by IL-4, IL-10 or PGE(2). M phi 2
      exhibit a unique molecular repertoire including receptors of innate immunity with
      broad specificity for foreign antigen and anti-inflammatory cytokines such as IL
      1 receptor antagonist and alternative macrophage activation-associated CC
      chemokine (AMAC)-1. While DC1 are well characterized, contradictory results have
      been obtained for DC2 that may either represent immature myeloid DCs or lymphoid
      DCs. Altogether, APC2 have come to age; they mediate Th2 differentiation,
      tolerance induction, downregulation of inflammation and healing. Thus, APC2
      represent a hitherto neglected, but indispensable major pathway of APC activation
      and function.

PMID- 11586069
TI  - Epidemiology of cutaneous melanoma in Germany and worldwide.
AB  - Rising incidence rates of cutaneous melanoma have been observed during the last
      three decades. At the beginning of the 1970s 3 cases and in the 1990s 9 cases per
      100,000 inhabitants and year were reported by the Saarland Cancer Registry in
      Germany. Other incidence studies from Germany in the 1990s even reported 10-12
      cases per 100,000 inhabitants and year, which is more likely to be the
      representative melanoma incidence in Western Germany. In a worldwide comparison
      this is a medium incidence rate as compared to clearly higher incidence rates in
      the United States (10-20 cases per 100,000 inhabitants and year) and in Australia
      (40-60 cases per 100,000 inhabitants and year). In Europe the highest incidence
      rates have been reported from Scandinavia (about 15 cases per 100,000 inhabitants
      and year) and the lowest from the Mediterranean countries (about 5-7 cases per
      100,000 inhabitants and year). Mortality rates likewise increased in Germany
      between 1970 and 1995 in males from 1.7 to 3.2 cases and in females from 1.6 to
      2.0 cases per 100,000 inhabitants and year. In the 1990s, in Germany and in many
      other countries a leveling off of mortality rates was observed. 48,928 melanoma
      patients have been recorded by the Central Malignant Melanoma Registry from the
      German-speaking countries in the time period from 1983 to September 2000, and
      clinico-epidemiological analysis of cutaneous melanoma is based on this data
      material. While 2/3 of all melanoma patients in Germany were females in the
      1970s, there is now a more balanced gender distribution with more than 45% of
      patients being males. Age distribution does not significantly change during the
      last three decades. Most melanomas are diagnosed in the age group between 50 and
      60 years, 22% of all melanomas are diagnosed before the 40th year of age. A clear
      decrease of Breslow's tumor thickness was found from the beginning of the 1980s
      to the mid-1990s with the median thickness decreasing from 1.3 to 0.8 mm. Lower
      Breslow's tumor thickness at first diagnosis of cutaneous melanoma has only been
      reported from Australia. This development indicates improved early recognition of
      cutaneous melanoma which is presently the main factor for a more favorable
      prognosis.

PMID- 11586070
TI  - Enhancement of the antiparakeratotic potency of calcitriol and tacalcitol in
      liposomal preparations in the mouse tail test.
AB  - In order to test the advantage of vitamin D(3) preparations in liposomal form,
      calcitriol, the natural activated form of vitamin D(3), and tacalcitol, a vitamin
      D(3) analogue, were employed in various concentrations and using different
      vehicles in the mouse tail test, an animal model for testing the
      antiparakeratotic efficacy of topical medications. The optimal concentration in
      petrolatum turned out to be similar to that in commercial preparations. The
      liposomal preparations were superior to those in petrolatum and to those in
      nonliposomal phospholipids. The antiparakeratotic potency (drug activity) of
      liposomal tacalcitol in a concentration of 2 microg/g was twice that of the
      commercial preparation with a higher concentration of 4 microg/g. These results
      suggest that the use of liposomal vitamin D(3) preparations can achieve a given
      antipsoriatic effect with a reduced concentration of the active substance thereby
      reducing the risk of skin irritation and of hypercalcemia.

PMID- 11586071
TI  - Relevance of oral supplementation with antioxidants for prevention and treatment
      of skin disorders.
AB  - Reactive oxygen species can cause harmful effects in keratinocytes and
      fibroblasts if antioxidative defence mechanisms are exhausted. Therefore, it
      seems to be reasonable to prove if oral supplementation with various nutrient
      antioxidants is useful in prevention or treatment of skin disorders especially in
      those mediated by UV irradiation. Betacarotene, ascorbic acid and tocopherol have
      been tested alone or in combination for prevention of sunburn, photodermatoses
      and photocarcinogenesis with divergent results. Other candidates for oral
      antioxidative supplementation in humans are selenium and polyphenols. However,
      clinical data are limited or missing up to date.

PMID- 11586073
TI  - Value of quantitative photoplethysmography for functional vascular diagnostics.
      Current status and prospects.
AB  - The paper presents recent advances in photoplethysmography (PPG) and the role
      played by PPG in the noninvasive diagnostics of venous and arterial disease. The
      technical principles of the new self-calibrating photoplethysmographs are
      explained. These units allow a quantitative evaluation of all measurement data
      (e.g. time values, amplitudes, flow rates, blood volume kinetics) and hence a
      precise analysis of both venous and arterial hemodynamics. In combination with
      appropriate tests (muscle pump test, vein occlusion test, noninvasive venous
      pressure test, arterial pulse and pressure test), they are suitable for
      diagnosing and assessing the severity of vascular disease and monitoring its
      course and the efficacy of therapy. Now that PPG has gained worldwide acceptance
      as a routine diagnostic technique for venous disease, its spectrum should be
      expanded to the arterial side as well.

PMID- 11586072
TI  - Retinoids--which dermatological indications will benefit in the near future?
AB  - Retinoids are compounds with pleiotropic functions and a relatively selective
      targeting of certain skin structures. They are vitamins, because retinol (vitamin
      A) is not synthesized in the body and must be derived from diet, but also
      hormones with intracrine activity, because retinol is transformed into molecules
      that bind to nuclear receptors, exhibit their activity, and are subsequently
      inactivated. Retinoids exert their effects on target cells by binding and
      activating nuclear retinoid receptors. Retinoid receptors bind their ligands in
      form of dimers. Heterodimers can be formed between two different retinoid
      receptor molecules but also between retinoid X receptors and the vitamin D
      receptor as well as the triiodothyronin receptor. This fact indicates complex
      interactions between retinoids and further hormonal signal transduction
      molecules. Interaction of retinoid receptors with transcriptional factors
      activated by other signal transduction mechanisms, e.g. AP-1, may provide
      dissociation of the retinoid effects. Retinoids can exhibit agonistic activity
      but also be neutral antagonists and inverse agonists. Topical and oral retinol,
      tretinoin, isotretinoin, and bexarotene, topical alitretinoin, retinaldehyde,
      motretinide, adapalene, tazarotene, and systemin acitretin compose the list of
      launched retinoids. Psoriasis and related disorders, congenital disorders of
      keratinization, acne, photoaging and hypovitaminosis A are classical approved
      indications of retinoid treatment, whereas cutaneous T-cell lymphoma, AIDS
      associated Kaposi's sarcoma, acute promyelocytic leukemia and actinic lentigines
      were currently confirmed. In addition, retinoids have been successfully used in
      several other dermatoses, e.g. epithelial precanceroses and tumors, seborrhea,
      rosacea and acneiform dermatoses, lichen planus, eosinophilic folliculitis,
      condylomata accuminata, lichen sclerosus and atrophicus. Highly receptor
      selective molecules, retinoic acid receptor-beta-inducers, AP-1 complex
      antagonists, and inverse agonists will be probably lead the retinoid development
      in the near future. New, more effective and less toxic retinoids, alone or in
      combination with other drugs and new delivery systems may provide therapeutic
      solutions for benign and malignant proliferative skin diseases, such as psoriasis
      and non-melanoma tumors, cancer chemoprevention and differentiation therapy.

PMID- 11586074
TI  - Current progress in phlebosurgery.
AB  - Modern operative varicosurgery is based on sophisticated diagnosis and surgical
      techniques protecting tissue to achieve optimized functional results combined
      with the best possible cosmetic success.

PMID- 11586075
TI  - Skin manifestations in solid organ transplant recipients.
AB  - The clinical spectrum of the most significant dermatological complications of
      solid organ transplantations is presented in an attempt to enhance the awareness
      among dermatologists and other physicians of the importance of careful
      dermatological monitoring of organ transplant recipients for early diagnosis and
      prompt treatment of these manifestations.

PMID- 11586076
TI  - A redescription of Chabaudus leberrei (Bain & Philippon, 1969) (Nematoda:
      Seuratoidea) from Xenopus spp. in Swaziland.
AB  - Chabaudus leberrei (Bain & Philippon, 1969) is redescribed from the pipid anurans
      Xenopus muelleri (Peters) and X. laevis laevis (Daudin) (new host records) in
      northern Swaziland, based on light and scanning electron microscope studies. The
      six anterior protuberances characteristic of the genus Chabaudus Inglis & Ogden,
      1965, are, in C. leberrei, formed by bipartite lamellae associated with the
      internal margins of the three lips. Intraspecific variation in the number and
      disposition of male caudal papillae and in the development of the cephalic
      vesicle is documented.

PMID- 11586077
TI  - Tormopsolus attenuatus n. sp. (Digenea: Acanthocolpidae) from Seriola hippos
      (Perciformes: Carangidae), Western Australia, with some observations on the
      relationships in the genus.
AB  - A new acanthocolpid, Tormopsolus attenuatus n. sp., is described from the
      carangid Seriola hippos from waters off the coast of SW Australia. A cladistic
      analysis of the genus using 31 morphological and metrical characters indicates
      that the closest species is T. asiatica Parukhin, 1976 status amend. (previously
      T. orientalis asiatica). T. attenuatus differs from T. asiatica in its smaller
      overall dimensions, more attenuated outline, relatively shorter post-testicular
      region, vitelline interruption at the level of the ovary, papillae on the oral
      sucker and, possibly, much longer genital atrium. Other similar species, T.
      orientalis Yamaguti, 1934 and T. medius Reimer, 1983, differ in having
      interruptions of the vitelline fields at the level of both testes and at the
      level of the ovary.

PMID- 11586078
TI  - DNA evidence that Marshallagia marshalli Ransom, 1907 and M. occidentalis Ransom,
      1907 (Nematoda: Ostertagiinae) from Svalbard reindeer are conspecific.
AB  - The gastro-intestinal parasitic nematodes of ruminants Marshallagia marshalli and
      M. occidentalis are morphs of a single species according to indirect evidence. In
      this study, their taxonomic status and molecular identification were assessed
      more directly in isolates from the abomasal nematode community of Svalbard
      reindeer using genetic data. DNA sequences of the first and second internal
      transcribed spacers of nuclear ribosomal RNA genes were obtained from individual
      nematodes by the polymerase chain reaction (PCR). Both taxa contained virtually
      identical sequences of each ITS and shared most of the polymorphisms detected. A
      PCR assay based on ITS-2 sequences previously developed to identify M. marshalli
      and Ostertagia gruehneri, the second common species in this community, gave
      identical results for M. marshalli and M. occidentalis. Genetic data thus
      confirmed that M. marshalli and M. occidentalis are conspecific.

PMID- 11586080
TI  - Scanning electron microscopy and intraspecific variation of Chordodes festae
      Camerano, 1897 and C. peraccae (Camerano, 1894) (Nematomorpha: Gordioidea).
AB  - The nematomorph species Chordodes festae Camerano, 1897 and C. peraccae
      (Camerano, 1894) are redescribed by using scanning electron microscopy (SEM). C.
      festae has a cuticle with four different areolar types, the crown areoles being
      the most noticeable with long spiniform processes. The terminal end in the male
      specimen has two short lobe-like structures and a ventral groove. C. peraccae has
      three areolar types in which, as in C. festae, some areoles form groups
      surrounding the crown areoles. Intraspecific variations were found in body length
      and body colour in both species and, in C. peraccae, also in the cuticle.

PMID- 11586079
TI  - Organisation of the praesoma of Paratenuisentis ambiguus (Van Cleave, 1921)
      (Acanthocephala: Eoacanthocephala), with special reference to the lateral sense
      organs and musculature.
AB  - The praesoma of the acanthocephalan parasite Paratenuisentis ambiguus was studied
      at the light and the electron microscope level, with special reference to the
      lateral sense organs and the musculature, in order to substantiate the basal
      pattern of the Acanthocephala and to analyse the phylogeny of the taxon. The
      study includes the first ultrastructural description of a lateral sense organ in
      the Acanthocephala. Two sensory support cell ducts extend from the binucleate
      pericaryon of the sensory support cell to the lateral sense organs. On their way
      to the lateral sense organs the ducts penetrate the receptacle and join the
      anterior ventral nerves. Each lateral sense organ consists of a conical
      termination of one of the sensory support cell ducts, in which the neuronal
      fibres and dendritic terminations of the equilateral anterior ventral nerve are
      embedded. An analysis of the available data of praesomal sense organs in
      Acanthocephala suggests that lateral and apical sense organs are absent in the
      basal pattern of the Acanthocephala. It is likely that two lateral sense organs,
      a binucleate sensory support cell with two ducts and two anterior ventral nerves
      evolved within the stem-line of some Palaeacanthocephala, all Eoacanthocephala
      and all Archiacanthocephala, whereas two apical sense organs, a quadrinucleate
      sensory support cell with four ducts and two apical sensory nerves presumably
      represent an autapomorphic character of the Archiacanthocephala. Furthermore, it
      can be derived from data in the literature and the present study that the
      praesomal hooks are totally covered by epidermis in the basal pattern of the
      Acanthocephala, whereas the ontogenetic loss of the epidermal covering can be
      regarded as an autapomorphy of the Archiacanthocephala.

PMID- 11586081
TI  - Comparative karyological studies on the species of Eubothrium Nybelin, 1922
      (Cestoda: Pseudophyllidea).
AB  - Karyotypes of Eubothrium salvelini, E. crassum and Eubothrium sp. were studied
      using conventional Giemsa staining and comparative karyometric analysis. The
      karyotypes, reported here for the first time, consist of eight chromosome pairs.
      The two first pairs of homologues are metacentric and markedly larger than the
      remaining elements. The obvious similarity in karyotype structure does not
      exclude the possibility of discriminating E. salvelini and E. crassum using
      karyotypic characters. The best cytogenetic marker is the last pair of
      chromosomes, which is acrocentric in the karyotype of E. salvelini and
      metacentric in that of E. crassum. Karyological observations provide strong
      evidence for assigning Eubothrium sp. from Clupea harengus membras to E. crassum.
      Comments are made on the karyotypes of these and related species with respect to
      their phylogenetic links.

PMID- 11586082
TI  - A redescription of Homalometron senegalense Fischthal & Thomas, 1972 (Digenea:
      Apocreadiidae) from Synaptura kleinii (Teleostei) of the western Mediterranean.
AB  - The apocreadiid digenean Homalometron senegalense is redescribed from the soleid
      fish Synaptura kleinii from off Corsica in the western Mediterranean. For the
      first time, lymphatic vessels are described for this species, and the
      implications of this in the systematics of the Apocreadiidae discussed. This
      species is considered closest to H. galaicus and H. wrightae, both also reported
      from soleid hosts. The concept of Apocreadiidae espoused is that most recently
      developed by Cribb & Bray (1999).

PMID- 11586083
TI  - Lecithophyllum kitrii n. sp. (Digenea: Lecithasteridae) from Australian coral
      reef fishes of the genus Siganus.
AB  - Lecithophyllum kitrii n. sp. is described from Siganus punctatus and S. lineatus
      off Heron Island on the southern Great Barrier Reef, Australia. It differs from
      most other species in the genus in its elongate pars prostatica and globular
      sinus-sac, and from all other species in having the seminal vesicle almost always
      entirely in the hindbody.

PMID- 11586084
TI  - Nectonema zealandica n. sp. (Nematomorpha: Nectonematoidea) parasitising the
      purple rock crab Hemigrapsus edwardsi (Brachyura: Decapoda) in New Zealand, with
      notes on the prevalence of infection and host defence reactions.
AB  - A new species of marine hairworm, Nectonema zealandica (Nematomorpha:
      Nectonematoidea), is described from the purple rock crab Hemigrapsus edwardsi
      Hilgendorf from the South Island, New Zealand. This is the first record of
      Nectonema in the South Pacific Ocean and the southernmost locality for the genus.
      The description is based on juveniles and pre-adults taken from crabs. The new
      species is characterised by its stomal structure, presence of four cephalic
      papillae, mesenchyme arranged in eight lobes in pre-adults, insertion of muscle
      layer increasing body diameter at the septum and translucent anterior chamber.
      Data on the prevalence of infection over a three-year period, rates of parasitism
      in relation to host sex and size, and host defence reactions are presented. A
      list of all reported hosts of nectonematids is included.

PMID- 11586091
TI  - Schedule-dependent pulsed paclitaxel radiosensitization for thoracic malignancy.
AB  - The objective of this study was to apply preclinical research of paclitaxel
      radiosensitization to the treatment of thoracic malignancy. Human lung cancer
      cell line NCI520 and epidermoid cell line A431 were investigated in vitro for
      radiosensitizing effects of paclitaxel. Optimal schedule of paclitaxel treatment
      was applied to a clinical protocol as well as off-protocol treatment of thoracic
      malignancy. Pulsed paclitaxel with concurrent once-daily radiation was delivered
      every 48 hours during the week using doses of 15 mg/m2, 20 mg/m2, or 25 mg/m2 in
      a phase I clinical trial of dose escalation. Preclinical data support the finding
      that low-dose paclitaxel is sufficient for radiosensitization. Data also support
      that delaying radiation is better than immediate radiation after drug treatment.
      Twenty-three patients have enrolled in the phase I clinical trial. Seventeen
      patients completed treatment (6 at 15 mg/m2; 5 at 20 mg/m2; and 6 at 25 mg/m2).
      Mean tumor shrinkage at 4 to 6 weeks after therapy was 82%, 84%, and 84% for dose
      levels I, II, and III, respectively [average primary tumor shrinkage was 83% +/-
      8% (95% C.I.)]. Locoregional tumor response rate was 100% [12% (2/17) complete
      response and 88% (15/17) partial response] with low rates of toxicity. It is
      concluded that pulsed low-dose paclitaxel and radiation is a very effective and
      well-tolerated regimen for thoracic malignancy.

PMID- 11586092
TI  - Targeting angiogenic processes by combination rofecoxib and ionizing radiation.
AB  - Tumor growth and angiogenesis are interdependent. Cyclooxygenase (COX) catalyzes
      the synthesis of prostaglandins from arachidonic acid. Nonsteroidal
      antiinflammatory drugs (NSAIDs) inhibit COX-mediated synthesis of prostaglandins.
      COX-1 is constitutively expressed in a wide range of tissues, whereas COX-2 is
      cytokine inducible. Enhanced COX-2 expression has been attributed a key role in
      the development of inflammation and related processes observed in pathologically
      altered disease states. Two specific COX-2 inhibitors, namely rofecoxib (Vioxx)
      and celecoxib (Celebrex), both oral agents and U.S. Food and Drug Administration
      approved, have been shown preclinically and clinically to have efficacy
      comparable to that of NSAIDs for relief of pain and inflammation in
      osteoarthritis, with decreased risk of gastrointestinal damage. Little is known
      about how angiogenesis is affected by the combination of rofecoxib and radiation.
      We have evaluated the combination of rofecoxib, at various concentrations, and
      radiation on cytokine-induced angiogenesis in vitro. We have found that rofecoxib
      inhibited endothelial cell proliferation, migration, and tube formation
      (differentiation) at clinically relevant doses. In combination with radiation,
      inhibition of endothelial cell function further increased twofold. The
      combination of rofecoxib and radiation suggests a complementary strategy with
      clinical ramifications to target angiogenesis-dependent malignancies.

PMID- 11586093
TI  - Elevated COX-2 expression in cervical carcinoma: reduced cause-specific survival
      and pelvic control.
AB  - The purpose of this study was to correlate the level of cyclooxygenase-2 (COX-2)
      expression in carcinoma of the cervix with the clinical endpoints: local control,
      cause-specific survival, and patterns of failure in patients treated with
      radiotherapy. Formalin-fixed, paraffin-embedded tumor biopsies were stained for
      COX-2. Clinical factors such as stage, grade, tumor size, pre- and posttreatment
      hemoglobin level, and radiotherapy dose were also evaluated. Actuarial local
      control rates and cause-specific survival were determined according to the Kaplan
      Meier method. COX-2 distribution staining was the only prognostic factor that was
      associated with local control and cause-specific survival. High COX-2
      distribution staining was associated with decreased local control and decreased
      cause-specific survival by log rank comparison of Kaplan-Meier survival curves.
      The 5-year cause-specific survival rates for tumors with low versus high COX-2
      distribution values were 90% and 22%, respectively (p = 0.0003). Actuarial pelvic
      control at 5 years was superior in patients with low COX-2 distribution staining
      (92%) compared with high staining (42%, p = 0.005). COX-2 staining intensity was
      found to correlate positively with tumor size (p = 0.02). These findings indicate
      that increased expression of COX-2 yields reduced pelvic control and cause
      specific survival in patients with invasive carcinoma of the cervix treated with
      radiotherapy. Previously, inhibition of COX-2 has been demonstrated to sensitize
      tumors to radiation without effect on normal tissue. Taken together, these data
      may support a novel therapeutic application of COX-2 inhibitors in the treatment
      of carcinoma of the cervix.

PMID- 11586094
TI  - Expression of inflammatory modulator COX-2 in pancreatic ductal adenocarcinoma
      and its relationship to pathologic and clinical parameters.
AB  - Despite the exceedingly poor prognosis of pancreatic cancer, it is often
      histologically well to moderately differentiated. The apparent resistance to
      conventional therapeutic modalities is poorly understood and may be related to
      the molecules involved in its progression or its propensity for perineurial
      invasion. Cyclooxygenase-2 (COX-2) is an inducible enzyme homologous to COX-1
      that is responsible for production of prostaglandins at sites of inflammation. It
      is activated by a variety of growth factors and tumor promoters, and it has been
      implicated in cancer progression. It may also have a role in the resistance to
      therapy. Anti-COX-2 agents have been documented to have antitumor activity, and
      some are now being tested in the therapy for various cancers, including those of
      the pancreas. Experience regarding the rate of COX-2 expression in pancreatic
      cancer and its relationship to the clinical and biologic parameters is very
      limited. In this study, immunohistochemical stains for COX-2 have been performed
      on 120 cases of pancreatic ductal adenocarcinoma. The stains were scored
      according to the percentage (0: no staining, 1: < 10%, 2: 10-50%, and 3: >50% of
      the cells staining) and intensity (0 for no staining, 1 for mild staining, and 2
      for dark staining) of staining. Based on the combined score for each case, they
      were divided into low expressors (percentage and intensity < or =1) and high
      expressors (percentage or intensity >1). In addition to global scoring for each
      case, the glandular and solid (poorly differentiated) components, when present,
      were scored separately. The global scores were correlated with clinical and
      biologic parameters. Seventy-four percent of the cases exhibited expression of
      COX-2 and 53% were high expressors. No significant association was observed when
      comparing the global COX-2 expression to survival, tumor size, stage, and
      vascular invasion. Increased perineural invasion was found to be significantly
      associated with COX-2 expression (p < 0.05). Increased expression was also more
      common in the glandular component as compared with the solid component of the
      tumors (68% versus 35%, p < 0.05). Of the 34 patients who received radiotherapy,
      9 were low expressor (median survival 19.5 months) and 25 were high expressors
      (median survival 14 months). The difference in survival was not statistically
      significant.

PMID- 11586095
TI  - Characterization of the effects of antiangiogenic agents on tumor
      pathophysiology.
AB  - A variety of strategies have been proposed to control tumor growth and metastasis
      by inhibiting tumor angiogenesis. To optimally combine such antiangiogenic
      approaches with conventional therapy, improved methods are needed to characterize
      the underlying pathophysiologic changes. The objective of the current work was to
      demonstrate the utility of a combination of recently developed
      immunohistochemical and image analysis techniques in quantitating changes in
      tumor vasculature and hypoxia. Murine MCa-35 mammary carcinomas were frozen after
      administration of two COX-2 inhibitors: meloxicam and celecoxib (Celebrex). Total
      blood vessels were visualized using anti-CD31 staining, perfused vessels by
      intravenous injection of DiOC7, and tumor hypoxia by EF5 uptake. Although both
      agents produced similar reductions in tumor volume compared with untreated
      tumors, varied effects on tumor vasculature and hypoxia were noted. Meloxicam
      reduced total vessel numbers significantly, whereas celecoxib had no effect. Both
      drugs substantially increased perfused vessel densities. Although mean hypoxic
      marker uptake was unchanged from matched controls, intratumor EF5 heterogeneities
      were significantly different between drugs. The results suggest that COX-2
      inhibitors can have varying effects on tumor pathophysiology. Successful use of
      these drugs to enhance radiation response will likely require optimization of
      drug choice, dose schedule, and direct physiologic monitoring.

PMID- 11586096
TI  - Hypoxia in human prostate carcinoma: an Eppendorf PO2 study.
AB  - The purpose of this study was to characterize the extent of hypoxia in human
      prostate carcinoma using the Eppendorf PO2 microelectrode. Custom-made Eppendorf
      PO2 microelectrodes were used to obtain PO2 measurements from the pathologically
      involved region of the prostate (as determined by the pretreatment sextant
      biopsies), as well as from a region of normal muscle for comparison. Fifty-nine
      patients with localized prostate cancer were studied, all of whom received
      brachytherapy implants under spinal anesthesia. A multivariate mixed effects
      analysis for prediction of tumor oxygenation was performed including the
      following covariates: type of tissue (prostate versus muscle), prostatic-specific
      antigen, disease stage, patient age and race, tumor grade, volume, perineural
      invasion, and hormonal therapy. Because of differences in patient
      characteristics, control measurements were obtained from normal muscle in all
      patients. This internal comparison showed that the oxygen measurements from the
      pathologically involved portion of the prostate were significantly lower (average
      median PO2 = 2.4 mm Hg) compared with the measurements from normal muscle
      (average median PO2 = 30.0 mm Hg), p < 0.0001. A multivariate, linear, mixed
      analysis demonstrated that the only significant predictor of oxygenation was the
      type of tissue (prostate versus muscle). This study, using in vivo electrode
      oxygen measurements, suggests that hypoxia exists in human prostate carcinoma.
      More patients will be accrued to this study to ultimately correlate the
      oxygenation status in prostate carcinoma tumors with treatment outcome.

PMID- 11586098
TI  - Hypoxic heterogeneity in human tumors: EF5 binding, vasculature, necrosis, and
      proliferation.
AB  - We evaluated the levels and distribution of hypoxia in 31 human tumors using
      fluorescent immunohistochemical detection of binding by the 2-nitroimidazole,
      EF5. Hypoxia was found to be a heterogeneous property of human tumors. Necrosis
      was usually found adjacent to the highest level of binding in an individual
      patient's tumor. However, hypoxia often occurred without necrosis. In the group
      of tumors studied, the most common relationship between blood vessels
      (PECAM/CD31) and EF5 staining was consistent with diffusion-limited hypoxia;
      acute hypoxia occurred infrequently. Within a given patient's tumor, there was an
      inverse correlation between regions of proliferation (Ki-67) and regions of
      hypoxia. Again, however, when these parameters were examined in a group of
      patients, the absence of proliferation did not predict the presence of hypoxia.
      The relationships between hypoxia and other biologic endpoints are complex, but,
      within a given tumor's spatial relationships, they are in accord with known
      physiologic principles. Thus, our data emphasize that the relationships between
      hypoxia and other biologic parameters vary between patients. Necrosis,
      proliferation, and blood vessel distribution cannot predict the level or presence
      of hypoxia in an individual patient's tumor.

PMID- 11586097
TI  - Prognostic radiology: quantitative assessment of tumor oxygen dynamics by MRI.
AB  - It is generally recognized that tumor hypoxia has a strong influence over
      therapeutic outcome in the clinic. The authors have developed an oximetry
      approach using 19F echo planar magnetic resonance imaging-FREDOM (Fluorocarbon
      Relaxometry using Echoplanar imaging for Dynamic Oxygen Mapping), which reveals
      dynamic changes based on sequential maps of regional tumor PO2. Preclinical
      investigations focused on diverse sublines of the Dunning prostate R3327 tumor.
      As expected, intratumoral heterogeneity was considerable. However, large tumors
      (>3.5 cm3) were significantly less well oxygenated than smaller tumors (<2 cm3).
      Faster growing, less differentiated tumors were less well oxygenated than size
      matched tumors of slower growing sublines. The greatest potential of this
      technique is the ability to follow the fate of individual tumor regions with
      respect to interventions. For each subline, there was a significant response to
      respiratory challenge with oxygen for initially well-oxygenated regions (baseline
      PO2 > 10 mm Hg). More interestingly, subline dependent behavior was found for
      initially hypoxic regions that correlated with rate of growth. The authors
      believe the FREDOM approach is essentially ripe for translation to the clinic.
      This approach could help to identify patients with hypoxic tumors and indicate
      the feasibility of manipulating tumor characteristics through adjuvant
      interventions to improve therapeutic response.

PMID- 11586100
TI  - Molecular pathways that modify tumor radiation response.
AB  - Aberrant expression of signal transduction molecules in pathways controlling cell
      survival, proliferation, death, or differentiation are a common feature of all
      tumors. The identification of the molecules that are involved allows the
      development of novel tumor-specific strategies. Not surprisingly, targeting these
      pathways often also results in radiosensitization. The efficacy of such directed
      therapies may, however, be limited by the heterogeneity and the multiple
      mutations that are associated with the cancerous state. A more robust alternative
      may be to target global mechanisms of cellular control. The ubiquitin/proteasome
      degradation pathway is one candidate for such therapeutic intervention. This
      pathway is the main posttranscriptional mechanism that controls levels of many
      short-lived proteins involved in regulation of cell cycle progression, DNA
      transcription, DNA repair, and apoptosis. Many of these proteins are involved in
      various malignancies and/or radiation responses. In recent years, proteasome
      inhibitors have gained interest as a promising new group of antitumor drugs. PS
      341, a reversible inhibitor of proteasome chymotryptic activity, is currently
      being tested in phase I clinical trials. In this study, we show that proteasome
      inhibition by PS-341 can alter cellular radiosensitivity in vitro and in vivo, in
      addition to having direct antitumor effects.

PMID- 11586099
TI  - Radiation-mediated control of drug delivery.
AB  - Clinical trials of radiotherapy to control drug delivery were initiated in 1999
      at Vanderbilt University. The initial studies exploited the findings that
      platelets are activated in tumor blood vessels after high-dose irradiation as
      used in radiosurgery and high-dose-rate brachytherapy. Platelets labeled with
      111In showed binding in tumor blood vessels. However, the platelet labeling
      process caused platelets to also accumulate in the spleen. That clinical trial
      was closed, and subsequent clinical trials targeted protein activation in
      irradiated tumor blood vessels. Preclinical studies showed that peptide libraries
      that bind within irradiated tumor blood vessels contained the peptide sequence
      Arg-Gln-Asp (RGD). RGD binds to integrin receptors (e.g., receptors for
      fibrinogen, fibronectin, and vitronectin). We found that the fibrinogen receptor
      (GPIIb/IIIa, alpha2bbeta3) is activated within irradiated tumor blood vessels.
      RGD peptidemimetics currently in clinical trials include GPIIb/IIIa antagonists
      and the platelet-imaging agent biapcitide. Biapcitide is an RGD mimetic that is
      labeled with 99Tc to allow gamma camera imaging of the biodistribution of the
      GPIIb/IIIa receptor in neoplasms of patients treated with radiosurgery. This
      study has shown that the schedule of administration of the RGD mimetic is
      crucial. The peptide mimetic must be administered immediately before irradiation,
      whereas the natural ligands to the receptor compete for biapcitide binding if
      biapcitide is administered after irradiation. The authors currently are
      conducting a dose deescalation study to determine the threshold dosage required
      for RGD mimetic binding to radiation activated receptor. Radiation-guided
      clinical trials have been initiated by use of high-dose-rate brachytherapy. In a
      separate trial, the pharmacokinetics of radiation-inducible gene therapy are
      being investigated. In this trial, the radiation-activated promoter Egr-1
      regulates expression of the tumor necrosis factor alpha gene, which is
      administered by use of the attenuated adenovirus vector. The Ad.Egr-TNF (ADGV)
      gene is administered by intratumoral injection of vector followed by irradiation
      in patients with soft-tissue sarcomas. This review highlights recent findings in
      these phase I pharmacokinetic studies of radiation-controlled drug delivery
      systems.

PMID- 11586101
TI  - Effects of p53 mutations on cellular sensitivity to ionizing radiation.
AB  - Mutations in the p53 tumor suppressor gene have been found in more than 50% of
      human tumors including those in breast, colon, lung, and oral cavity. However,
      the significance of p53 mutation in radiation sensitivity and its underlying
      mechanisms still remains unclear. In this study, we have measured the effects of
      p53 mutation on cell cycle delay, apoptosis, and radiation sensitivity using
      mouse cells transfected with different forms of p53 mutations. Wild-type p53 and
      p53-Null mouse embryo fibroblast cells were used as positive and negative
      controls, respectively. Exponentially growing cells were irradiated with 0- to 9
      Gy gamma rays and then assayed for cell survival, p53 expression, cell cycle
      checkpoint, and apoptosis. Cell survivals determined by clonogenic assay show
      that p53 mutant cells are generally more sensitive to ionizing radiation than
      cells with wild-type p53. Western blot analysis indicates that exposure to 6-Gy
      gamma rays increases the p53 expression levels by two- to threefold in wild-type
      p53 cells. However, the p53 level remains unchanged in cells with mutant p53
      during the same postirradiation period. Irradiation with 6-Gy gamma rays produces
      G2/M arrest in all cell lines, indicating that p53 is probably not involved in
      the G2/M checkpoint. However, all mutant cells fail to show any significant G1/S
      arrest after irradiation, suggesting that G1/S arrest may be implicated in
      radiation sensitivity. Finally, there is very little apoptosis (<3% by Tat
      mediated dUTP nick-end labeling [TUNNEL] and morphologic assays) detected in wild
      type and p53 mutant cell lines after 6-Gy gamma rays. Our results suggest that
      mutant forms of p53 represent a phenotype that affects the radiation sensitivity
      and is not dependent on the apoptotic pathway.

PMID- 11586102
TI  - Keratinocyte growth factors radioprotect bowel and bone marrow but not KHT
      sarcoma.
AB  - Various members of the fibroblast growth factor (FGF) family of proteins have
      been shown to protect against acute and late radiation damage of normal tissues.
      Protection of the small bowel, for example, occurs via both increased
      proliferation and reduced apoptosis. Other beneficial effects of FGFs include
      promotion of bone growth, pneumonitis prevention, and apoptosis suppression of
      endothelium in vivo and in vitro after irradiation. This protection against
      radiation requires only low and infrequent doses of FGFs. Two newly identified
      members of the FGF family, FGF7 and FGF10, have effects similar to many of the
      other FGF family proteins, but with more specificity for normal epithelial
      structures. For this reason, they have also been named keratinocyte growth
      factors one and two (KGF1 and KGF2, respectively). We therefore examined the
      potential utility of KGFs for radioprotection of the bone marrow and small bowel
      and examined safety issues concerning their adverse effects on KHT sarcoma. The
      results suggest that KGFs could be safely used to prevent radiation toxicity of
      the abdomen or pelvis and may in fact improve tumor response to radiation.

PMID- 11586103
TI  - Overexpression of the HER-2/neu oncogene in pancreatic adenocarcinoma.
AB  - Novel systemic treatments are needed in pancreatic cancer. The authors sought to
      establish the frequency of overexpression of the HER-2/neu oncogene in patients
      with pancreatic adenocarcinoma to determine the potential role of trastuzumab
      (Herceptin) as a therapeutic agent in this disease. Tumor specimens from patients
      with pancreatic adenocarcinoma were analyzed by staining for p185HER2 protein
      using the DAKO immunohistochemical assay. Patients with and without HER-2/neu
      overexpression by immunohistochemistry were compared with respect to clinical and
      pathologic characteristics. HER-2/neu gene amplification was also evaluated by
      fluorescence in situ hybridization (FISH). Thirty-two of 154 patients (21%) had
      pancreatic adenocarcinoma that demonstrated HER-2/neu overexpression by
      immunohistochemistry. At initial diagnosis, 16% of resectable cancers, 17% of
      locally advanced cancers, and 26% of metastatic cancers were determined to have
      HER-2/neu overexpression. Three of 11 (27%) patients with HER-2/neu
      overexpression by immunohistochemistry had gene amplification by FISH. HER-2/neu
      overexpression occurs in a subset of pancreatic cancer. Evaluation of the
      efficacy of trastuzumab for patients with pancreatic cancer who overexpress HER
      2/neu appears indicated.

PMID- 11586104
TI  - Early growth response-1 gene: potential radiation response gene marker in
      prostate cancer.
AB  - This study was undertaken to determine whether the transcription factor EGR-1
      expression: (1) in the primary tumor, correlates with radiation response in terms
      of complete local tumor control with no evidence of disease or recurrence and no
      evidence of metastasis; (2) in the postirradiated biopsies correlates with
      residual tumor; and (3) correlates with the expression of Egr-1 target genes such
      as TP53, pRB, and Bax. The authors analyzed: (1) 25 pretreated surgically
      resected paraffin-embedded primary adenocarcinomas of the prostate for the
      presence of EGR-1 expression and mutation, and correlated this with clinical
      endpoints such as serum prostate-specific antigen levels and current clinical
      status; (2) 27 postirradiated biopsies of prostate for the presence of EGR-1
      expression, and correlated these findings to the residual tumor status; and (3)
      12 prospective prostate tumor specimens for EGR-1 expression and its target
      genes. EGR-1 expression was determined by immunohistochemistry and mutations were
      screened in two regions of the Egr-1 gene (trinucleotide AGC repeats in
      transactivation domain [TD] and poly A tract in 3'UTR) by polymerase chain
      reaction-single strand conformational polymorphism analysis. Of 25 patients, 18
      patients showed expression of EGR-1. EGR-1 overexpression correlated with
      treatment failure. No correlation with EGR-1 overexpression and its target genes
      was found, which may indirectly suggest that overexpressed EGR-1 may lack
      transactivation function. In summary, EGR-1 overexpression in the mutant form may
      provide an indication of clinical failure (local recurrence or metastasis).

PMID- 11586105
TI  - Pilot evaluation of 1p and 19q deletions in anaplastic oligodendrogliomas
      collected by a national cooperative cancer treatment group.
AB  - Radiation Therapy Oncology Group (RTOG) trial 94-02 is designed to compare the
      effectiveness of radiation therapy alone with radiation therapy plus
      procarbazine, lomustine, and vincristine (PCV) chemotherapy in patients with
      anaplastic oligodendrogliomas and mixed oligoastrocytomas. This prospectively
      collected, randomly treated, prospectively followed cohort is the ideal set of
      patients to validate the observation that anaplastic oligodendrogliomas with 1p
      and 19q deletions have a prolonged survival and a better response to
      chemotherapy. For patients entered on RTOG 94-02, fresh blood specimens, as well
      as slides and paraffin blocks, have been obtained (with informed consent) on
      enrollment. Peripheral blood leukocytes (buffy coats) have been frozen and stored
      and Epstein-Barr-virus-immortalized lymphoblastoid lines have been prepared from
      the blood specimens. In this report, the authors describe a pilot 1p/19q deletion
      analysis of 26 tumors from RTOG trial 94-02. In this analysis, it is shown that
      1p/19q deletion analysis by fluorescence in situ hybridization is feasible on
      blocks collected from this trial. Also demonstrated is that the incidence of 1p
      and 19q deletions in this pilot series of anaplastic oligodendrogliomas and mixed
      oligoastrocytomas is similar to that reported in previous studies. When the
      clinical follow-up on this prospective trial is mature and the deletion studies
      have been completed, the authors should be able to determine whether 1p and 19q
      deletions predict a prolonged survival and/or responsiveness to PCV chemotherapy
      plus radiation in patients with anaplastic oligodendrogliomas and mixed
      oligoastrocytomas.

PMID- 11586106
TI  - Chromatin compaction and tumor cell radiosensitivity at 2 gray.
AB  - Mammalian cells at mitosis, differentiated lymphocytes, and some radiation
      hypersensitive mutants in interphase contain all or a measurable portion of their
      chromatin in condensed/compacted form and are hypersensitive to ionizing
      radiation by the mechanism described by single-hit inactivation kinetics (alpha).
      These observations led to the investigation as to whether compacted chromatin in
      interphase is the target that determines the widely variable alpha-parameters and
      surviving fractions of 2 Gy (SF2Gy) measured for human tumor cell lines. Six cell
      lines whose SF2Gy ranged from 0.29 to 0.73 were used for this study. Their
      different radiosensitivities were associated mainly with differences in their
      single-hit inactivation parameters (alpha). Electron microscope images of
      interphase nuclei were optically scanned, and the pixel densities were digitized
      for quantitative analyses. A significant correlation between the percentage of
      nuclear pixels with densities similar to those found in mitotic chromosomes
      (percent compacted chromatin) and the alpha-inactivation parameters was observed.
      Digital analyses of electron and/or confocal microscope images of chromatin in
      interphase tumor cells in biopsy specimens could become a rapid assay for
      predicting the intrinsic radiosensitivity of tumor clonogens. This research has
      also identified some inhibitors of protein (histone) phosphatases that promote
      chromatin compaction and radiosensitize cells to 2-Gy dose fractions.

PMID- 11586108
TI  - In vivo proton (H1) magnetic resonance spectroscopy for cervical carcinoma.
AB  - Proton magnetic resonance spectroscopy (MRS) may be a useful tool in both the
      initial diagnosis of cervical carcinoma and the subsequent surveillance after
      radiation therapy, particularly when other standard diagnostic methods are
      inconclusive. Single voxel magnetic resonance (MR) spectral data were acquired
      from 8 normal volunteers, 16 patients with cervical cancer before radiation
      therapy, and 18 patients with cervical cancer after radiation therapy using an
      external pelvic coil at a 1.5-T on a Signa system. The presence or absence of
      various resonances within each spectrum was evaluated for similarities within
      each patient group and for spectral differences between groups. Resonances
      corresponding to lipid and creatine dominated the spectrum for the eight normal
      volunteers without detection of a choline resonance. Spectra from 16 pretreatment
      patients with biopsy-proven cervical cancer revealed strong resonances at a
      chemical shift of 3.25 ppm corresponding to choline. Data acquired from the 18
      posttreatment setting studies was variable, but often correlated well with the
      clinical findings. Biopsy confirmation was obtained in seven patients. H1 MRS of
      the cervix using a noninvasive pelvic coil consistently demonstrates reproducible
      spectral differences between normal and neoplastic cervical tissue in vivo.
      However, signal is still poor for minimal disease recurrence. Further study is
      needed at intervals before, during, and after definitive irradiation with biopsy
      confirmation to validate the accuracy of MRS in distinguishing persistence or
      recurrence of disease from necrosis and fibrosis.

PMID- 11586107
TI  - Interstitial fluid pressure in cervical cancer: guide to targeted therapy.
AB  - Interstitial fluid pressure (IFP) is elevated in most malignant tumors, mainly as
      a result of the abnormal tumor vasculature that develops from unregulated
      angiogenesis. Theoretical models predict that IFP should correlate with capillary
      flow resistance in tumors, and therefore also with perfusion and oxygenation.
      However, a prospective clinical study in patients with cervical cancer at
      Princess Margaret Hospital failed to demonstrate a relationship between IFP and
      oxygenation. Despite this, high IFP was strongly associated with inferior
      survival after radiotherapy independent of clinical prognostic factors and tumor
      oxygen status. This suggests that IFP and direct needle oxygen measurements may
      provide information about different aspects of tumor oxygenation, such as chronic
      versus intermittent hypoxia. Alternatively, IFP may reflect an aspect of tumor
      biology that is largely unrelated to perfusion and oxygenation. One possibility
      is that tumors with high pretreatment angiogenesis levels, as indicated by high
      IFP, may be more radioresistant because the vascular endothelium is more likely
      to survive during and after treatment. The mechanistic link between elevated IFP
      and the abnormal tumor vasculature and the strong prognostic effect of IFP in our
      cervix study together suggest that drugs targeted at angiogenesis, when combined
      with radiotherapy, may lead to improved tumor control and patient survival.

PMID- 11586109
TI  - Choosing dopamine agonists in Parkinson's disease.
AB  - Dopamine agonists (DAs) have been shown to be effective as monotherapy in early
      stages of Parkinson's disease (PD) and as an adjunctive treatment to levodopa in
      advanced PD. Since bromocriptine, an ergot compound, was introduced as the first
      commercially available DA more than 25 years ago, additional DAs have become
      available for clinical use. There is a remarkable paucity of data, however, that
      would guide clinicians in their decision process to select the most appropriate
      DAs. We discuss the theoretical basis for comparing the various DAs, and provide
      a concise analysis and summary of comparative trials of DAs in PD.

PMID- 11586110
TI  - Acute spinal cord injury, part I: pathophysiologic mechanisms.
AB  - Spinal cord injury (SCI) is a devastating and common neurologic disorder that has
      profound influences on modern society from physical, psychosocial, and
      socioeconomic perspectives. Accordingly, the present decade has been labeled the
      Decade of the Spine to emphasize the importance of SCI and other spinal
      disorders. Spinal cord injury may be divided into both primary and secondary
      mechanisms of injury. The primary injury, in large part, determines a given
      patient's neurologic grade on admission and thereby is the strongest prognostic
      indicator. However, secondary mechanisms of injury can exacerbate damage and
      limit restorative processes, and hence, contribute to overall morbidity and
      mortality. A burgeoning body of evidence has facilitated our understanding of
      these secondary mechanisms of injury that are amenable to pharmacological
      interventions, unlike the primary injury itself. Secondary mechanisms of injury
      encompass an array of perturbances and include neurogenic shock, vascular insults
      such as hemorrhage and ischemia-reperfusion, excitotoxicity, calcium-mediated
      secondary injury and fluid-electrolyte disturbances, immunologic injury,
      apoptosis, disturbances in mitochondrion function, and other miscellaneous
      processes. Comprehension of secondary mechanisms of injury serves as a basis for
      the development and application of targeted pharmacological strategies to confer
      neuroprotection and restoration while mitigating ongoing neural injury. The first
      article in this series will comprehensively review the pathophysiology of SCI
      while emphasizing those mechanisms for which pharmacologic therapy has been
      developed, and the second article reviews the pharmacologic interventions for
      SCI.

PMID- 11586112
TI  - Ambulatory objective assessment of tremor in Parkinson's disease.
AB  - Continuous ambulatory multichannel accelerometry (CAMCA) has recently been
      validated for the assessment of hypo-and bradykinesia and body position in
      patients with Parkinson's disease (PD). This study aims to validate CAMCA for the
      assessment of resting tremor in patients with PD. First, in seven patients with
      PD with varying degrees of tremor severity, a tremor detection algorithm was
      developed. Second, 59 patients with PD and 43 age-matched controls were assessed
      with CAMCA during 24 hours. Duration and intensity of resting tremor, and
      measures reflecting hypo-and bradykinesia and body position were calculated for
      the diurnal period. In part 1 of the study, the tremor detection algorithm had a
      high sensitivity (0.82) and specificity (0.93). Ambulatory monitoring revealed
      that categories with higher clinical tremor severity had increased objective
      values for duration and intensity of tremor. Duration and intensity of tremor
      were correlated with the clinical score for resting tremor (Spearman's rank
      correlation: 0.66-0.77). Measures for hypo-and bradykinesia differed between
      patients and controls, but not between groups of patients defined by tremor
      severity. This study has validated continuous ambulatory multichannel
      accelerometry for the assessment of tremor in PD, while simultaneously measuring
      hypo-and bradykinesia and body position.

PMID- 11586111
TI  - Acute spinal cord injury, part II: contemporary pharmacotherapy.
AB  - Spinal cord injury (SCI) remains a common and devastating problem of modern
      society. Through an understanding of underlying pathophysiologic mechanisms
      involved in the evolution of SCI, treatments aimed at ameliorating neural damage
      may be developed. The possible pharmacologic treatments for acute spinal cord
      injury are herein reviewed. Myriad treatment modalities, including
      corticosteroids, 21-aminosteroids, opioid receptor antagonists, gangliosides,
      thyrotropin-releasing hormone (TRH) and TRH analogs, antioxidants and free
      radical scavengers, calcium channel blockers, magnesium replacement therapy,
      sodium channel blockers, N -methyl-D-aspartate receptor antagonists, alpha-amino
      3-hydroxy-5-methylisoxazole-4-propionic acid-kainate receptor antagonists,
      modulators of arachadonic acid metabolism, neurotrophic growth factors, serotonin
      antagonists, antibodies against inhibitors of axonal regeneration, potassium
      channel blockers (4-aminopyridine), paclitaxel, clenbuterol, progesterone,
      gabexate mesylate, activated protein C, caspase inhibitors, tacrolimus,
      antibodies against adhesion molecules, and other immunomodulatory therapy have
      been studied to date. Although most of these agents have shown promise, only one
      agent, methylprednisolone, has been shown to provide benefit in large clinical
      trials. Given these data, many individuals consider methylprednisolone to be the
      standard of care for the treatment of acute SCI. However, this has not been
      established definitively, and questions pertaining to methodology have emerged
      regarding the National Acute Spinal Cord Injury Study trials that provided these
      conclusions. Additionally, the clinical significance (in contrast to statistical
      significance) of recovery after methylprednisolone treatment is unclear and must
      be considered in light of the potential adverse effects of such treatment. This
      first decade of the new millennium, now touted as the Decade of the Spine, will
      hopefully witness the emergence of universal and efficacious pharmacologic
      therapy and ultimately a cure for SCI.

PMID- 11586113
TI  - Clinical and electroencephalographic effects of topiramate in patients with
      epilepsy and healthy volunteers.
AB  - Although topiramate, one of the newer drugs used in treating epilepsy, is
      effective in reducing seizure frequency and has a wide spectrum of action, it
      often induces intolerable adverse effects, predominantly related to the central
      nervous system. Information that would help document adverse reactions early,
      thus allowing topiramate doses to be adjusted during the drug titration and
      maintenance phases, could be obtained from electroencephalogram (EEG) studies. We
      studied the clinical effects and EEG changes induced by topiramate in patients
      with refractory partial epilepsy receiving the drug as add-on therapy. To exclude
      effects related to the other drugs and to epilepsy itself, we compared data from
      patients and healthy volunteers. After receiving topiramate, 22.6% of patients
      became seizure free and 29% had their seizures reduced by 50% or more. Topiramate
      nevertheless induced noteworthy adverse reactions, the main problems being
      sedative and cognitive changes. Also, in healthy volunteers, a single 100-mg dose
      of topiramate induced mild adverse reactions, mainly affecting concentration and
      attention, with difficulties in speech and writing. In patients with epilepsy,
      the EEG changes induced by topiramate consisted of increased delta and theta
      activities and decreased activity in the rapid bands. This recognizable
      topiramate-induced EEG pattern was again evident in the healthy volunteers, in
      whom we also detected a significant reduction in the alpha frequency rhythm. Our
      results confirm that topiramate needs to be introduced gradually while patients
      undergo close neuropsychologic and neurophysiologic monitoring to detect adverse
      sedative and cognitive reactions early. The EEG correlate of these events seems
      to be increased activity in the slower frequency bands.

PMID- 11586114
TI  - Topiramate improves deficit symptoms in a patient with schizophrenia when added
      to a stable regimen of antipsychotic medication.
AB  - Topiramate was shown to attenuate the severity of negative symptoms (e.g.,
      emotional withdrawal) in a patient with schizophrenia when added to his stable
      regimen of antipsychotic medication. Topiramate was administered for a period of
      12 weeks; during the first 4 weeks, dosage was adjusted to the maximal tolerated
      dose ( i.e., 175 mg/d), and, thereafter, this dosage was maintained for 8 weeks.
      Topiramate was studied because of recent data and hypotheses suggesting that N
      methyl-D-aspartate receptor hypofunction, dampened GABAergic inhibition, and
      excessive stimulation of the kainic acid (KA)/alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA) class of glutamate receptors occur in at
      least some patients with schizophrenia, especially those with persistent negative
      symptoms and progressive psychosocial deterioration. Topiramate is a recently
      approved and marketed medication for the treatment of seizure disorders, whose
      mechanism of action includes potentiation of GABAergic neurotransmission and
      antagonism of KA/AMPA glutamate receptors. This case is presented because of the
      dramatic response of negative symptoms to the addition of topiramate. The
      severity of negative symptoms was assessed formally with the Negative Scale of
      the Positive and Negative Syndrome Scale. The negative symptoms of schizophrenia
      are usually resistant to most behavioral and pharmacologic interventions.

PMID- 11586115
TI  - Long-term comparative experience with tolcapone and entacapone in advanced
      Parkinson's disease.
AB  - The objective of this study was to compare the long-term tolerability and
      efficacy of tolcapone and entacapone in patients with fluctuating Parkinson's
      disease (PD). Tolcapone and entacapone are two currently available catechol- O 
      methyltransferase inhibitors that have demonstrated efficacy in the treatment of
      advanced PD. There are little published data on long-term experience and no
      direct comparisons. We compared the results of two separate, simultaneous, long
      term open label extensions, one for tolcapone and the other for entacapone. The
      inclusion/exclusion criteria were similar. Data were collected prospectively at
      6, 12, 24, and 36 months. Efficacy measures included the Unified Parkinson's
      Disease Rating Scale (UPDRS) total score, subscores, items 32 (duration of
      dyskinesia) and 39 (duration of "off" time), and levodopa dose. The two groups
      were compared using a Mann-Whitney U test for change from baseline and analysis
      of variance. Tolerability was defined as the ability of patients to maintain
      therapy and was compared using a Kaplan-Meier analysis. Eleven patients enrolled
      in the entacapone study and 14 in the tolcapone study. The tolcapone group had
      more severe disease with significantly higher UPDRS motor score, duration of
      "off," and levodopa dose requirement. Tolcapone was more effective in lowering
      UPDRS motor and complication subscores, duration of "off" time, and levodopa
      doses. UPDRS motor scores and change in levodopa dose in the tolcapone group
      remained below baseline level for 36 months; however, they were above baseline in
      the entacapone group from 6 months on. Tolerability was the same for both
      treatments. Tolcapone appears to have greater and longer efficacy with regard to
      motor symptoms, "off" time, and change in levodopa requirements than entacapone.
      These findings indicate that tolcapone continues to have a place in the treatment
      of advanced PD. However, the risks associated with this drug, particularly
      hepatic injury, and the requirement for rigorous blood monitoring, need to be
      considered when choosing an appropriate treatment for patients with advanced PD.

PMID- 11586116
TI  - Acute mania and hemichorea.
AB  - A 61-year-old man suddenly became euphoric and talkative. Later the same day, he
      developed hemichoreic movements of the left limbs. The patient fulfilled the DSM
      IV criteria for a manic episode by abnormally and persistently elevated mood,
      decreased need for sleep, high distractibility, pressured speech, increased goal
      directed activity, and hypersexuality. The mood changes persisted for several
      weeks. Magnetic resonance imaging of the brain showed a right thalamic
      infarction. The co-occurrence of hemichorea and mania caused by focal thalamic
      lesion is very rare. It may be explained by dysfunction in basal ganglia
      thalamocortical circuitry.

PMID- 11586117
TI  - Bitemporal epileptiform discharges induced by bupropion: a case report.
AB  - We report the case of a 44-year-old right-handed woman who experienced her first
      convulsion while taking bupropion. Electroencephalography showed frequent
      bilateral independent temporal lobe epileptiform discharges that resolved when
      bupropion was discontinued. This is the first well-documented case of
      epileptiform discharges induced by bupropion in humans.

PMID- 11586135
TI  - Assessment of cervical ligamentous injury in trauma patients using MRI.
AB  - During a 7-year period, a consecutive retrospective series of 89 trauma patients
      at a Level One trauma center who had negative standard radiographs with suspected
      occult cervical injury were administered a cervical magnetic resonance imaging
      (MRI) scan. The MRI studies were fully able to assess the ligamentous status of
      the cervical spine in all patients and were the final step in determining the
      treatment of the spine. Of the total 89 patients, 82 had no ligamentous injury,
      and 7 had ligamentous injury. Two patients underwent surgery because of the
      findings on the MRI study. MRI studies of patients with negative standard
      radiographs but with suspected occult cervical injury are excellent and safe
      studies for the evaluation of cervical spinal stability because of their ability
      to detect ligamentous injuries that are not evident on plain radiographs.

PMID- 11586136
TI  - Simultaneous anterior-posterior thoracolumbar spine surgery.
AB  - The purpose of this article is to report our experience with simultaneous
      anterior and posterior approach spine surgery. The patient is placed in the
      decubitus position. Two teams of spine surgeons simultaneously perform surgical
      approaches, decompression, arthrodesis, and instrumentation. No repositioning,
      repreparing, or redraping is necessary. Twelve patients with varying lesions
      underwent this procedure. This technique is presented as an alternative to the
      sequential single-staged anterior and posterior procedure and the two-staged
      procedures performed under separate anesthetics. Although no statistical
      significance can be concluded, we believe a larger series will demonstrate that
      operative time is decreased, potential risks of repositioning are avoided, and
      superior exposure and mobilization of spinal elements are afforded. Exposure,
      decompression, and stabilization posteriorly is feasible in the decubitus
      position.

PMID- 11586137
TI  - Anterior lumbar interbody fusion using a barbell-shaped cage: a biomechanical
      comparison.
AB  - There are drawbacks to using threaded cylindrical cages (e.g., limited area for
      bone ingrowth and metal precluding radiographic visualization of bone healing).
      To somewhat offset these drawbacks, a barbell-shaped cage has been designed. The
      central core of the barbell can be wrapped with collagen sheets infiltrated with
      bone morphogenetic protein. The obvious theoretical advantages of a barbell cage
      have to be weighed against potential biomechanical disadvantages. Our purpose was
      to compare the biomechanical properties of an anterior lumbar interbody
      reconstruction using 18-mm-diameter threaded cylindrical cages, with a
      reconstruction using barbell cages (18-mm diameter and 6 mm wide at both
      cylindrical ends, with a round 4-mm-diameter bar joining the two ends). Twelve
      cadaveric lumbar motion segments were tested. Three L5-S1 segments received two
      threaded cylindrical cages, and three L5-S1 segments received two barbell cages.
      Three L3-L4 segments received one threaded cylindrical cage, and three L3-L4
      segments received one barbell cage. A series of biomechanical loading sequences
      were carried out on each motion segment, and stiffness curves were obtained.
      After the biomechanical testing, an axial compressive load was applied to the
      motion segments until failure. They were then radiographed and bisected through
      the disc, and the subsidence (or penetration) of the cage(s) in the cancellous
      bone of the vertebral bodies was measured. There was no difference in terms of
      stiffness between the motion segments with the threaded cylindrical cage(s)
      inserted and those with the barbell cage(s) inserted (p > 0.15). The average
      values of subsidence was 0.96 mm for the threaded cylindrical cage group and 0.80
      mm for the barbell cage group (difference not significant: p = 0.38). The results
      suggest that a reconstruction using barbell cages is a biomechanically acceptable
      alternative to one using threaded cylindrical cages.

PMID- 11586138
TI  - Treatment of osteoporotic late collapse of a vertebral body of thoracic and
      lumbar spine.
AB  - Although osteoporotic late collapse of a vertebral body is a common infirmity of
      old age, it has not been well studied, and no consensus regarding treatment of
      this condition has been reached. Forty-five patients with osteoporotic late
      collapse of a vertebral body were classified into six types based on the
      appearance on the lateral projection of a radiograph and the presence or absence
      of neurologic symptoms and were evaluated on imaging and clinical outcome. We
      concluded that the treatment of osteoporotic late collapse of a vertebral body
      can be individualized based on several factors such as the presentation of the
      fracture and neurologic condition. Conservative treatment can be selected in
      patients without neurologic involvement who have the concave type with anterior
      spur or sclerotic change or flat type with uniform compression of collapse. If
      the patients in those types of collapse show neurologic involvement,
      decompression and reconstruction through a posterior approach, including an
      eggshell procedure and the short segment pedicle screw system, are more suitable.
      Anterior decompression with anterior strut bone graft and anterior spinal
      instrumentation should be done for wedged type of collapse regardless of
      neurologic status.

PMID- 11586139
TI  - Improving the pullout strength of pedicle screws by screw coupling.
AB  - The objective of this study was to determine the effect of pedicle screw coupling
      on the pullout strength of pedicle screws in the osteoporotic spine. The
      vertebral bone mineral density (BMD) of 33 cadaveric lumbar vertebrae were
      measured by quantitative computed tomography. Pedicle screws were inserted into
      each pedicle. The pullout strength and displacement of the screws, without
      coupling and with single or double couplers, were studied, and the relationship
      between pullout strength and BMD was analyzed. The average pullout strength of
      the pedicle screws without screw coupling was 909.3 +/- 188.6 N (n = 9), that
      coupled with a single coupler was 1,409.0 +/- 469.1 N (n = 9), and that with
      double couplers was 1,494.0 +/- 691.6 N (n = 9). The pullout strength of the
      screws coupled with single or double couplers was significantly greater than that
      of screws without couplers (p < 0.01); however, there was no significant
      difference between the groups of single and double couplers. The improvement of
      pullout strength by screw coupling was significant in a test group with BMD of
      more than 90 mg/ml (p < 0.01), but was not in the group with BMD less than 90
      mg/ml (p = 0.55). These results suggest that the coupling of pedicle screws
      improves pullout strength; however, the effect tends to be less significant in
      severely osteoporotic spines.

PMID- 11586140
TI  - Clinical symptoms and surgical outcome in lumbar spinal stenosis patients with
      neuropathic bladder.
AB  - We evaluated the clinical and radiologic features of patients with lumbar spinal
      stenosis with neuropathic bladder. Based on cystometrogram analysis, the patients
      were divided into two groups--the neuropathic bladder (NB) group: the NB+ group
      (23 patients), and the nonneuropathic bladder group: the NB- group (14 patients).
      The symptom of incontinence was characteristic in patients in the NB+ group.
      Patients in the NB+ group had a more severe neurologic disturbance, compared with
      those in the NB- group. The more severe neurologic disturbance was caused by the
      more striking finding of degenerative spinal stenosis associated with
      developmental narrowing of the spinal canal. Decompressive surgery had a
      beneficial effect on the recovery of the neurologic symptoms in both groups.
      Residual urine volume was reduced after surgery. Postoperative cystometrogram was
      carried out in nine patients in the NB+ group. It showed a normal pattern in six
      patients; however, three patients remained in an underactive pattern.
      Furthermore, four patients still required clear intermittent self-catheterization
      after surgery.

PMID- 11586141
TI  - Long-term disability assessment after surgical treatment of low grade
      spondylolisthesis.
AB  - The aim of this study was to determine whether assessment of back surgery with
      disability scores is relevant. We also attempted to answer the question of
      whether this evaluation should be conducted by a surgeon or a medical doctor.
      This retrospective study analyzes the long-term outcome (average follow-up 7
      years, range: 3-12) of 40 patients (mean age: 46.2 years) treated by posterior
      surgical decompression, posterolateral arthrodesis, with or without
      instrumentation, for symptomatic low-grade spondylolisthesis. All patients were
      interviewed postoperatively and examined the same day by an orthopedic surgeon,
      who was not involved in the patients' treatment, as well as by a medical doctor
      rehabilitation specialist. Impairment was assessed by a standardized clinical
      examination and by visual analog scales (VAS) of pain. Disability was assessed
      using two scales: the Quebec disability scale and the Beaujon scale. Anxiety and
      depression were assessed with a validated specific questionnaire (HAD). Patient's
      perceived handicap was assessed on a 100-mm VAS. Our results show that the scores
      of the two disability scales were highly correlated with the patient's overall
      satisfaction ( r = 0.73 and 0.77 for the Quebec scale and the Beaujon scale,
      respectively). The intraclass correlation coefficient showed very good or
      excellent correlation between the data collected by the surgeon and the
      rehabilitation specialist, ranging from 0.8 to 0.97. This finding clearly
      demonstrates that interview by a surgeon who is not involved in the patient's
      treatment does not influence the patient's assessment in terms of impairment,
      disability, or handicap. Moreover, our results suggest that disability scales are
      the most relevant outcome measures in the assessment of spine surgery.

PMID- 11586142
TI  - Health-related quality of life after short segment instrumentation of lumbar
      burst fractures.
AB  - Management of lumbar burst fractures remains controversial. Surgical
      reduction/stabilization is becoming more popular; however, the functional impact
      of operative intervention is not clear. The purpose of this study was to assess
      health-related quality of life and functional outcome after posterior fixation of
      lumbar burst fractures with either posterolateral or intrabody bone grafting.
      Twenty-four subjects were included. Radiographs and computed tomography scans
      were evaluated for deformity (kyphosis, vertebral compression, lateral
      angulation, lateral body height, and canal compromise) postoperatively, at 1
      year, and at final follow-up (mean 3.2 years). Patients completed the SF 36
      Health Survey and the Oswestry Low Back Pain Disability Questionnaire at final
      follow-up. Significant improvement was noted in midsagittal diameter compromise,
      vertebral compression, and kyphosis. The difference observed between the
      respondents mean scores on the SF 36 was not significantly different from those
      presented as the U.S. national average (p = 0.053). Data from the Oswestry
      questionnaire indicated a similarly high level of function. Overall, we found
      posterior spinal instrumentation to correlate with positive functional outcome
      based on both general health (SF 36) and joint-specific outcome scales
      (Oswestry). Posterior instrumentation provides sound canal decompression,
      kyphotic reduction, and maintains vertebral height with minimal transgression and
      long-term sequelae. In cases of severe initial deformity and neurologic
      compromise, intrabody bone grafting is most certainly indicated; the additional
      support provided by a posterolateral graft may also prove beneficial as an
      adjunct.

PMID- 11586143
TI  - Cauda equina syndrome in ankylosing spondylitis (the CES-AS syndrome): meta
      analysis of outcomes after medical and surgical treatments.
AB  - The cauda equina syndrome in ankylosing spondylitis (the CES-AS syndrome) is
      marked by slow, insidious progression and a high incidence of dural ectasia in
      the lumbosacral spine. A high index of suspicion for this problem must be
      maintained when evaluating the patient with ankylosing spondylitis with a history
      of incontinence and neurologic deficit on examination. There has been
      disagreement in the literature as to whether surgical treatment is warranted for
      this condition. A meta-analysis was thus performed comparing outcomes with
      treatment regimens. Our results suggest that leaving these patients untreated or
      treating with steroids alone is inappropriate. Nonsteroidal antiinflammatory
      drugs may improve back pain but do not improve neurologic deficit. Surgical
      treatment of the dural ectasia, either by lumboperitoneal shunting or
      laminectomy, may improve neurologic dysfunction or halt the progression of
      neurologic deficit.

PMID- 11586144
TI  - Roentgenographic evaluation of ossification and calcification of the lumbar
      spinal canal after intradiscal betamethasone injection.
AB  - There have been reports of lumbar spinal canal ossification and calcification
      after triamcinolone intradiscal injection therapy. Our objective was to observe
      the roentgenographic changes after betamethasone intradiscal injection therapy
      for lumbar disc diseases. The subjects were 183 patients (498 discs; 130 men and
      53 women) who underwent discography and betamethasone intradiscal injection
      therapy and were followed for a mean of 5 years and 7 months. Ossification and
      calcification appeared de novo (three patients, three discs) or enlarged (four
      patients, five discs) in the outer layer of the posterior annulus fibrosus or
      posterior longitudinal ligament in eight discs among seven patients (3.8%). The
      incidence and degree of ossification and calcification in our patients were
      significantly lower than those reported in previous studies, and a long time
      elapsed before ossification and calcification appeared or enlarged. Intradiscal
      injection of betamethasone did not appear to confer any incremental relative risk
      for lumbar spinal canal ossification and calcification based on review of follow
      up roentgenographs.

PMID- 11586145
TI  - Evaluation of thoracic myelopathy by transcranial magnetic stimulation.
AB  - It is sometimes difficult to determine the appropriate surgical site in patients
      with thoracic myelopathy with diffuse or multisegmental lesions. To solve this
      problem, a magnetic stimulation study was carried out. Seven patients with
      myelopathy and 10 healthy control subjects were examined. Transcranial magnetic
      stimulation was applied and the motor evoked potentials (MEPs) of the intercostal
      muscles were recorded. The MEP latencies for the two groups were then compared.
      In patients with thoracic myelopathy, the MEP latencies caudal to the lesion were
      more extended than those of the control subjects. This method could identify the
      levels at which myelopathy originates in patients with a radiologically visible
      lesion. This method has the potential to be used for deciding the surgical site
      at the level responsible for myelopathy in cases with multiple or diffused
      compression.

PMID- 11586146
TI  - A new application of TCE-MEP: spinal cord monitoring in patients with severe
      neuromuscular weakness undergoing corrective spine surgery.
AB  - The importance of spinal cord monitoring during corrective scoliosis surgery is
      widely acknowledged. However, for patients with preoperative neurologic deficits,
      its use is technically difficult. In this article, we describe intraoperative
      transcranial electrical motor evoked potential (TCE-MEP) monitoring in nine
      patients with neuromuscular weakness who underwent corrective scoliosis surgery.
      In each patient, eight muscle groups were recorded and stable responses were
      obtained in all patients. We conclude that TCE-MEP permits monitoring of the
      spinal cord in patients with disturbed motor function.

PMID- 11586147
TI  - Effect of stimulation parameters on intraoperative spinal cord evoked potential
      monitoring.
AB  - The purpose of this study was to investigate the effects of the stimulus
      parameters on spinal cord evoked potential (SCEP) and to recommend a practical
      epidural stimulation protocol for intraoperative spinal cord monitoring. This
      prospective study compared the latencies and amplitudes of SCEP obtained on
      epidural stimulation of 30 patients with scoliosis under anesthesia using
      different stimulus pulse duration and stimulation rates. SCEP was found to be
      undetectable with shorter stimulus duration (<0.05 ms). The SCEP latencies did
      not show any significant difference among different stimulation parameters.
      However, the SCEP amplitude showed significant changes with differing stimulus
      durations. The SCEP amplitudes were found to significantly decrease when the
      pulse durations become shorter than 0.2 ms. Stimulus parameters showed
      significant effects on SCEP amplitude but not latency. Stimulus rates in the
      range of 21 to 61 Hz are equivalent for quick and reliable detection of SCEP.
      Considering the short latency of SCEP, a pulse duration of 0.2 ms is recommended
      for SCEP using epidural stimulation.

PMID- 11586148
TI  - The penetration of cefoperazone and sulbactam into the lumbar intervertebral
      discs.
AB  - Six patients received 1 g and six other patients received 2 g of cefoperazone and
      sulbactam 15 minutes before lumbar disc surgery. Liquid chromatographic analysis
      of disc tissue revealed that only patients receiving the 2-g dose had mean tissue
      levels above the minimum inhibitory concentration for Staphylococcus aureus and
      epidermidis.

PMID- 11586149
TI  - C2 dens fractures: treatment options.

PMID- 11586150
TI  - Hemorrhagic shock induced up-regulation of P-selectin expression is mediated by
      factors in mesenteric lymph and blunted by mesenteric lymph duct interruption.
AB  - BACKGROUND: Previous studies have shown that mesenteric lymph duct interruption
      prevents lung injury and decreases lung neutrophil sequestration after
      hemorrhagic shock (HS). Since endothelial cells rapidly express P-selectin after
      ischemia/reperfusion injury and HS-induced lung injury appears to involve
      neutrophil-endothelial cell interactions, we tested the following two hypotheses.
      First, that HS increases endothelial cell P-selectin expression and that
      interruption of mesenteric lymph flow in vivo would diminish this expression.
      Second, that incubation of human umbilical vein endothelial cells with post-HS
      mesenteric lymph but not sham shock (SS) lymph or postshock portal vein plasma
      would up-regulate P-selectin expression. METHODS: Pulmonary microvascular P
      selectin expression was measured in male rats subjected to 90 minutes of HS (30
      mm Hg), SS, or HS with lymphatic ligation, with a dual radiolabeled monoclonal
      antibody technique. The lungs from these animals were subsequently harvested and
      P-selectin expression was expressed as mean +/- SEM nanograms of monoclonal
      antibody per gram of tissue. RESULTS: Pulmonary P-selectin expression was 2.0 +/-
      0.4 after SS, 9.7 +/- 3.0 after HS, but decreased to 2.3 +/- 0.3 after HS with
      lymph interruption (p < 0.05 HS vs. SS or HS plus lymph ligation). Incubation of
      human umbilical vein endothelial cells with shock lymph collected 3 to 4 hours
      after shock resulted in a nearly fivefold increase in P-selectin expression (p <
      0.001) as compared with SS lymph, lymph collected 6 hours after shock, or
      postshock portal vein plasma. CONCLUSION: These results support the concept that
      gut-derived lymph promotes HS-induced lung injury through up-regulation of
      microvascular adhesion molecules and that intestinal lymph duct interruption may
      prevent distant organ injury by blunting the expression of these molecules.

PMID- 11586151
TI  - The 15-year evolution of an urban trauma center: what does the future hold for
      the trauma surgeon?
AB  - BACKGROUND: Safer cars, decreased violence, and nonoperative management have
      changed the trauma patient's nature. We evaluated changes in a Level I trauma
      center over 15 years and considered their effect on trauma surgeons. METHODS:
      From January 1985 through August 1999, 16,799 trauma registry patients were
      analyzed for mechanism of injury, Injury Severity Score, and procedures. RESULTS:
      Mean Injury Severity Score decreased from 15.9 to 10.7 and length of stay fell
      from 8.0 days to 5.9 days. There were significant decreases in penetrating trauma
      admissions and percentage of patients with Abbreviated Injury Scale score > 3 for
      head, chest, and abdomen. Frequency of craniotomy, thoracotomy, and laparotomy
      dropped dramatically. CONCLUSION: Significant decreases in injury severity,
      penetrating violence, and operations have occurred over 15 years. These changes
      will have profound effects on the practice of trauma surgeons and on surgical
      education.

PMID- 11586152
TI  - Platelet activation and function after trauma.
AB  - BACKGROUND: Abnormal hemostasis is associated with many of the complications of
      trauma-associated morbidity and mortality. Platelets are integral in the
      maintenance of hemostasis. METHODS: Samples were obtained from 100 trauma
      patients on arrival at the emergency room (initial time) and at 24, 48, and 72
      hours later. Samples were also obtained from 10 healthy controls at the same time
      intervals. Using flow cytometry, three parameters were used to measure platelet
      activation: platelet microparticles, expression of P-selectin (CD62P), and
      expression of the activated conformation of glycoprotein IIb-IIIa (PAC-1
      binding). Platelet function was measured using a platelet function analyzer (PFA
      100, Dade International Inc., Miami, FL). RESULTS: One hundred trauma patients
      were enrolled. The average age was 40 years, 75% were men, and 84% had blunt
      injuries. The mean Injury Severity Score was 22.3 +/- 10.9 (mean +/- SD) and the
      average Glasgow Coma Scale score was 11 +/- 4. All three platelet activation
      parameters were increased in trauma patients versus controls for all time periods
      (p < 0.001). Trauma patients had a trend toward a shorter initial
      collagen/epinephrine closure time versus controls (p = 0.096). Compared with the
      24-, 48-, and 72-hour time intervals, initial collagen/epinephrine closure times
      were shortened (p < 0.001, p < 0.001, and p < 0.001). Platelet function returned
      to normal reference ranges within 24 hours but platelet activation parameters
      remained elevated at least 72 hours after initial trauma. In contrast, when
      trauma patients with and without brain injury were compared, brain injury
      patients had increased platelet activation but decreased platelet function
      (increased collagen/epinephrine closure times). In addition, there was a
      significant prolongation in collagen/epinephrine closure times for the 24-, 48-,
      and 72-hour time points in nonsurviving patients versus survivors. There was no
      association between platelet activation and function and other adverse outcomes
      including pulmonary embolism, deep venous thrombosis, and disseminated
      intravascular coagulation. CONCLUSION: Severe injury usually results in increased
      platelet activation and function. However, the combination of increased platelet
      activation with decreased function was associated with increased mortality.

PMID- 11586153
TI  - Role of duodenography in the diagnosis of blunt duodenal injuries.
AB  - BACKGROUND: The differentiation of duodenal perforation from duodenal hematoma is
      not always possible with computed tomography (CT). Our diagnostic guideline has
      included duodenography to investigate CT findings of periduodenal fluid or wall
      thickening. However, the utility of duodenography as a diagnostic study in blunt
      abdominal trauma is not defined. We evaluated duodenography as a diagnostic test
      in patients with suspected blunt duodenal injuries (BDIs). METHODS: During a 10
      year period, 96 patients out of 25,608 trauma admissions had CT findings of
      possible BDI and underwent duodenography. Demographic and clinical data,
      diagnostic methods, and management were derived from prospectively collected
      data. CT and duodenography studies were reviewed and correlated with surgical
      findings and outcome. All CT scans were obtained with intravenous contrast; oral
      contrast was used in 32 patients. Duodenography was analyzed using the 2 x 2
      method and Bayes theorem. RESULTS: Indications for duodenography included
      periduodenal fluid without extravasation (76%), abnormal duodenal wall thickening
      (16%), and retroperitoneal extraluminal gas (5%). Eighty-six duodenography
      studies were reported as normal, six were consistent with hematoma, one was
      indeterminate, and only three revealed extravasation. Two of these three patients
      with duodenal perforation had retroperitoneal extraluminal air. Only one patient
      underwent exploration on the basis of duodenography. No blunt duodenal
      perforation was diagnosed by CT. Overall, duodenography had sensitivity of 54%
      and specificity of 98%. For BDIs requiring repair, duodenography sensitivity was
      only 25%; the false-negative rate was also 25%. Retroperitoneal extraluminal air
      was a useful sign of duodenal perforation, occurring in two of three patients
      with BDI and only in one without BDI (p < 0.001). CONCLUSION: Duodenography has a
      low sensitivity in patients with suspected BDI by CT findings and is of minimal
      utility in diagnostic evaluation. Retroperitoneal extraluminal air seen on CT is
      an important sign of BDI requiring surgical repair.

PMID- 11586154
TI  - A new cervical spine clearance protocol using computed tomography.
AB  - OBJECTIVE: The purpose of this study was to assess a cervical spine clearance
      protocol for blunt trauma patients using helical computed tomographic (CT) scan
      of the cervical spine (C-spine). METHODS: A protocol using CT scan of the C-spine
      was implemented and the first 6 months of use reviewed. Patients requiring a CT
      scan of the head had the C-spine evaluated by lateral C-spine radiography and a
      helical CT scan. Patients without indication for CT scan of the head had the C
      spine evaluated by three-view radiography (anteroposterior, lateral, and
      odontoid) with selective CT scan of the C-spine for imaging areas not well
      visualized or those with abnormalities identified by radiography or by clinical
      examination alone. RESULTS: Three hundred twenty-four patients were admitted to
      the trauma center after blunt trauma during the first 6 months of protocol
      implementation. Head CT scans were obtained in 158 patients and lateral cervical
      spine radiography in conjunction with helical CT scanning evaluated the C-spine.
      The other 166 patients had the cervical spine cleared by three-view radiography
      series or by clinical examination alone. For patients in whom a head CT scan was
      not indicated, CT scanning was used only when plain radiographs failed to
      adequately visualize the entire C-spine. A total of 15 injuries (4.6% of the
      group) were detected. Seven injuries were suspected or detected by lateral plain
      radiographs and confirmed by CT scan. Six patients had an injury not detected by
      radiography but diagnosed by CT scan, and one patient had a false-positive
      radiograph. Of the remaining two injuries, one was diagnosed by magnetic
      resonance imaging and the other by CT scan outside of the protocol. Lateral plain
      radiographs alone failed to detect 46% (n = 6) of all injuries. CONCLUSION: In
      our series, the selective use of helical CT scanning with plain radiography
      increased the accuracy with which cervical spine injury was detected from 54% to
      100%. The protocol allowed for more rapid evaluation in many patients as well. We
      recommend that practice guidelines include the use of helical CT scan of the
      entire C-spine as the diagnostic procedure for those blunt trauma patients
      undergoing CT scanning of the head.

PMID- 11586155
TI  - Cervical spine injuries among submersion victims.
AB  - BACKGROUND: Submersion victims are frequently considered at high risk for
      cervical spine (C-spine) injury regardless of whether they sustain a traumatic
      injury. We hypothesized that C-spine injury is unlikely in submersion victims who
      do not sustain high-impact injuries. METHODS: The study was a cohort study of all
      people who submerged between January 1974 and July 1996 and received medical care
      or were seen by the medical examiner in King, Pierce, and Snohomish counties in
      Washington State. RESULTS: Eleven (0.5%) of 2,244 submersion victims had C-spine
      injuries. All 11 had submerged in open bodies of water; had clinical signs of
      serious injury; and had a history of diving, motorized vehicle crash, or fall
      from height. No C-spine injuries occurred in 880 low-impact submersions.
      CONCLUSION: Submersion victims are at risk for C-spine injury only if they have
      also sustained a traumatic injury. Routine C-spine immobilization does not appear
      to be warranted solely on the basis of a history of submersion.

PMID- 11586156
TI  - Prospective comparison of admission computed tomographic scan and plain films of
      the upper cervical spine in trauma patients with altered mental status.
AB  - OBJECTIVE: The accurate evaluation of patients with multiple injuries is
      logistically complex and time sensitive, and must be cost-effective. We
      hypothesize that computed tomographic (CT) scan of the upper cervical spine
      (occiput to C3 [Co-C3]) would add little to the initial evaluation of patients
      with multiple injuries who have altered mental status. METHODS: The study
      consisted of a prospective, unblinded, consecutive series. Patients met entry
      criteria if they had sustained a blunt mechanism of injury and had an altered
      mental status requiring CT scan of two or more body systems. All patients
      received CT scan of Co-C3 with 2-mm cuts and subsequent reconstructions as well
      as five-view cervical spine plain films. Cervical spine injury was defined as any
      radiographically identified fracture or subluxation that required treatment.
      Patients were excluded if they died or were cleared clinically before plain film
      series were obtained. CT scan of Co-C3 and cervical spine films were reviewed by
      two different attending radiologists. RESULTS: Of the 2,690 consecutive
      admissions between December 1998 and November 1999, 1,356 patients met entry
      criteria. Seventy patients (5.2%) had a total of 95 injuries to the upper
      cervical spine. CT scan of Co-C3 identified 67 of 70 patients and plain films
      identified 38 of 70 patients with injuries to the upper cervical spine. Twelve
      patients (17%) had neurologic deficits attributable to Co-C3 injuries. Three
      patients had false-negative CT scans of Co-C3, and one patient was quadriplegic.
      There were 32 patients with false-negative plain films, including four patients
      with motor deficits (one with quadriplegia). Use of the guidelines developed by
      the Eastern Association for the Surgery of Trauma identified all patients with
      upper cervical spine injuries; to date, no patient in the study group was
      readmitted or has initiated a lawsuit for missed injury of the upper cervical
      spine. CONCLUSION: CT scan of Co-C3 was superior to plain films in the early
      identification of upper cervical spine injury. Plain films failed to identify 45%
      of upper cervical spine injuries; four of these missed injuries resulted in motor
      deficits. Our study supports the practice guidelines developed by the Eastern
      Association for the Surgery of Trauma for clearance of the upper cervical spine
      in patients with altered mental status, as all patients with injuries were
      identified using these guidelines.

PMID- 11586157
TI  - Current opinion regarding indications for emergency department thoracotomy.
AB  - BACKGROUND: Emergency department thoracotomy (EDT) is a dramatic but rarely
      lifesaving intervention. Clinical variability regarding indications for EDT has
      yet to be quantified. Members of the Eastern and American Associations for the
      Surgery of Trauma were questioned by mail to evaluate which clinical and
      demographic factors influence the decision to perform EDT and whether physicians
      perform EDT in accordance with current practice guidelines. METHODS: A single
      mailing of an anonymous survey was sent to 1,124 surgeons to collect
      institutional and physician demographics as well as indications for EDT on the
      basis of variable mechanisms of trauma, duration of arrest, and signs of life
      (SOL). Statistical analysis included the Pearson and linear-by-linear association
      chi(2) tests, independent samples t test, and univariate and multivariate
      analyses of variance; p values of < 0.05 were considered significant. RESULTS:
      Completed surveys were received from 358 respondents. After 54 surveys were
      excluded that were incomplete, late, or from noneligible respondents, 304 surveys
      were analyzed. There were no significant differences in EDT indications among
      institutions of differing caseload volume, exposure to penetrating trauma, trauma
      level designation, American College of Surgeons verification status, or residency
      program affiliation. In addition, neither the respondent's position nor whether
      attendings versus residents performed the majority of EDTs influenced clinical
      decision-making. Performance criteria for EDT were liberal in comparison with
      established guidelines, especially for blunt trauma. The presence or recent loss
      of SOL influenced responses, but respondents varied greatly in their definition
      of SOL. CONCLUSION: A lack of agreement exists regarding the indications for EDT
      in multiple clinical scenarios as well as in defining SOL. Indications for EDT
      were liberal, especially for blunt trauma-related indications, and were
      determined by clinical parameters, not by physician or institutional factors. Our
      results suggest that clinical practice is at variance with Advanced Trauma Life
      Support guidelines. We recommend that practice guidelines for EDT be established
      on the basis of a consensus definition of SOL to allow for a more uniform and
      selective approach to EDT.

PMID- 11586158
TI  - A population-based study on pneumothorax in severely traumatized patients.
AB  - BACKGROUND: Pneumothorax (PNX) is a recognized cause of preventable deaths in
      trauma patients. Our objective was to determine the incidence of traumatic PNX,
      the characteristics of its victims, and the treatment they receive. METHODS: The
      study consisted of data set of a population-based study on major trauma. RESULTS:
      The incidence of PNX was 81 per 1 million population per year, mostly caused by
      transport accidents. PNX victims generally had multiple injuries, and they showed
      on-scene clinical parameters worse than victims of other chest injuries of
      comparable severity. Fifty-three percent of PNXs were drained during the
      prehospital and early (< 2 hours) hospital course. There was no uniformity of
      treatment among different types of rescue facilities, some of them never
      performing decompression despite clinical need. The z statistic for mortality was
      -0.63. CONCLUSION: PNX can be expected in one in five major trauma victims found
      alive. PNX is associated with a peculiar on-scene instability. Early
      decompression is often required. The effects of wider access to prehospital
      decompression and the reasons for its uneven availability in our setting need
      elucidation. Nevertheless, the present mortality follows the international
      standards.

PMID- 11586159
TI  - Bladder rupture after blunt trauma: guidelines for diagnostic imaging.
AB  - PURPOSE: The purpose of this study was to establish guidelines for diagnostic
      imaging for bladder rupture in the blunt trauma victim with multiple injuries, in
      whom the delay caused by unnecessary testing can hamper the trauma surgeon and
      threaten outcome. METHODS: We undertook chart review (1995-1999) of patients with
      blunt trauma and bladder rupture at our four institutions and performed focused
      literature review of retrospective series. RESULTS: Of our 53 patients
      identified, all had gross hematuria and 85% had pelvic fracture. Literature
      review revealed similar rates. CONCLUSION: The classic combination of pelvic
      fracture and gross hematuria constitutes an absolute indication for immediate
      cystography in blunt trauma victims. Existing data do not support lower urinary
      tract imaging in all patients with either pelvic fracture or hematuria alone.
      Clinical indicators of bladder rupture may be used to identify atypical patients
      at higher risk. Patients with isolated hematuria and no physical signs of lower
      urinary tract injury may be spared the morbidity, time, and expense of immediate
      cystographic evaluation.

PMID- 11586160
TI  - Median, ulnar, and combined median-ulnar nerve injuries: functional outcome and
      return to productivity.
AB  - BACKGROUND: Forearm and wrist injuries are a common cause of morbidity and are
      often associated with suboptimal recovery of hand function. This study describes
      and compares outcome after median, ulnar, or combined median-ulnar nerve
      injuries. METHODS: Three hundred thirteen wrist and forearm nerve injuries
      operated on between 1980 and 1997 in a large university hospital were reviewed in
      relation to complications, return to work, and sensor and motor recovery. Of
      these 313 patients, 220 (age range, 5-73 years) met the inclusion criteria.
      RESULTS: Motor recovery, progress of sensory reinnervation, and number of severed
      structures were related to the type of injury (p < 0.05). Multiple linear
      regression analysis revealed a relation between the appearance of sensory
      reinnervation and motor recovery (beta = 0.02; 95% confidence interval, 0.01
      0.04; p = 0.01). A probability of 24% of work loss, after a mean follow-up of
      17.7 months, was found. Poor sensory and motor recovery were associated with work
      disability (odds ratio [OR], 2.9; p = 0.002; and OR, 2.9; p = 0.007,
      respectively). No relationship was found between type of injury and return to
      work (p = 0.47). Level of injury (OR, 2.6; p = 0.01), type of work (OR, 3.1; p =
      0.002), number of complications (p < 0.001), and hand-therapy (OR, 0.24; p =
      0.001) were found to influence return to work. CONCLUSION: It may be concluded
      that peripheral nerve injuries at the forearm level can result in substantial
      functional loss and have major social consequences. This study identified factors
      influencing return to work that can be used to optimize postoperative treatment
      strategy.

PMID- 11586162
TI  - Increased peak contact stress after incongruent reduction of transverse
      acetabular fractures: a cadaveric model.
AB  - BACKGROUND: The objective of this study was to determine the peak contact
      pressure with varying degrees of articular cartilage step-off in a transtectal
      acetabular fracture model. METHODS: Five fresh frozen cadaveric hip joints were
      potted in a custom loading fixture. The five specimens were then tested at loads
      of 445 N (newton) (100 lb) and 1,335 N (300 lb) intact and after a transverse
      osteotomy at step-off levels from 0 to 5 mm in 1-mm increments. RESULTS:
      Articular cartilage step-off of greater than 1 mm led to significantly increased
      contact stress at the loaded acetabular articular surface. Mean peak pressure
      measured at 1,335 N of loading in all intact specimens before the osteotomy was
      approximately 10 MPa. Peak pressure after a transverse acetabular fracture did
      not change when the fracture was perfectly reduced. At 1 mm of step-off, the peak
      pressure increased by approximately 20% but was not statistically significant.
      With step-off of > 2 mm or greater, the peak pressure increase was approximately
      50% and was statistically significant. CONCLUSION: On the basis of our study,
      transverse acetabular fractures with greater than 1 mm of displacement can lead
      to significant increase in peak pressure at the articular surface.

PMID- 11586161
TI  - Low-intensity pulsed ultrasound in the treatment of nonunions.
AB  - BACKGROUND: Low-intensity ultrasound has demonstrated an acceleration of bone
      healing and more profound callus formation in animal and human clinical
      experiments. In this study, the effect of pulsed, low-intensity ultrasound was
      determined in established nonunion cases. METHODS: The enrolled cases were
      reviewed for the time from their last surgical procedure and evidence of no
      healing or progression of healing during the 3 or more months before the start of
      low-intensity ultrasound therapy to determine whether the cases were established
      nonunions. Twenty-nine cases, located in the tibia, femur, radius/ulna, scaphoid,
      humerus, metatarsal, and clavicle, met the criteria for established nonunions. On
      average, the postfracture period before the start of ultrasound treatment was 61
      weeks. Initial fracture treatment was conservative in 8 cases and operative in 21
      cases. Additional treatments including bone grafting, reosteosynthesis, and other
      surgical procedures were performed an average of 52 weeks before the start of
      ultrasound treatment. Daily, 20-minute applications of low-intensity ultrasound
      at the site of the nonunion were performed by the patients at home. RESULTS:
      Twenty-five of the 29 nonunion cases (86%) healed in an average treatment time of
      22 weeks (median, 17 weeks). Stratification of the healed and failed outcome for
      age, gender, concomitant disease, bone location, fracture age, prior last surgery
      interval, nonunion type, smoking habits, and fixation before and during treatment
      showed a significant difference only in the smoking habit strata. CONCLUSION:
      Noninvasive ultrasound therapy can be useful in the treatment of challenging,
      established nonunions.

PMID- 11586163
TI  - Treatment of femoral shaft aseptic nonunion associated with plating failure:
      emphasis on the situation of screw breakage.
AB  - BACKGROUND: Femoral shaft aseptic nonunions associated with plating failure
      resulting from screw breakage are rare, and the treatment is complex and yet to
      be defined. The aim of this prospective study was to develop a better technique
      for the treatment of this complication. METHODS: Eight consecutive adult patients
      who sustained femoral shaft aseptic nonunions associated with plating failure
      resulting from screw breakage were treated. The procedure involved skeletal
      traction in the femoral condyle, removal of the broken screws after making a bony
      window in the lateral cortex, with or without lengthening the femur,
      stabilization with a static locked nail, and finally, corticocancellous bone
      grafting. Postoperatively, ambulation with protected weight bearing was
      encouraged as early as possible. RESULTS: All eight patients were followed up for
      at least 1 year (range, 1.1-4.7 years), and seven nonunions healed. The median
      union period was 4 months (range, 3-6 months). One patient had a persistent
      nonunion, and the locked nail broke at 6 months. The nonunion healed 4 months
      after closed revision with a new locked nail. CONCLUSION: The described technique
      has both theoretical and clinical merits. All abnormalities can be corrected
      concomitantly. The success rate is high and the complication rate is low.
      Whenever possible, therefore, it may be used to treat all indicated cases of
      nonunion.

PMID- 11586164
TI  - The complex triplane fracture: ipsilateral tibial shaft and distal triplane
      fracture.
AB  - BACKGROUND: The complex triplane fracture (ipsilateral tibial shaft and distal
      tibial triplane fracture) is a rare combination. It has not previously been
      described in the literature. This combination can be easily overlooked and has
      the potential for serious sequelae if it is missed. METHODS: Six patients, having
      sustained this combined injury, were reviewed at a tertiary children's hospital.
      Clinical assessment, radiographs, computed tomographic scans, bone age, and
      scanogram assessment of leg length at maturity were completed. RESULTS: Average
      age at injury was 14 years. Tibial fractures were midshaft or short oblique.
      There were 3 three-part and 3 two-part intra-articular distal tibial triplane
      fractures. Diagnosis of the distal triplane fracture was delayed in two cases.
      Treatment involved application of a long leg cast. No patients required open
      reduction. At follow-up (average, 22 months), all patients were asymptomatic. All
      fractures were well healed and there was no evidence of joint incongruity, or
      angular or rotational deformity. Leg length discrepancy averaged 6.8 mm.
      CONCLUSION: A high index of suspicion should be maintained to avoid missing this
      rare combination, as it has the potential for long-term sequelae.

PMID- 11586165
TI  - Low-impact falls: demands on a system of trauma management, prediction of
      outcome, and influence of comorbidities.
AB  - BACKGROUND: Falls from a low height are an extremely common source of injury, the
      severity of which is often underestimated. As a result, low fall patients are
      usually not transferred to Level I trauma centers. There are surprisingly few
      systematic data relating to the demands made on systems of trauma care by
      patients with low falls. This study addresses this issue using information from a
      comprehensive national trauma database. The performance of TRISS methodology, and
      the factors associated with prolonged hospital stay, in low fall patients is also
      examined. METHODS: The study included 31,419 patients. Patients with low falls (<
      2 m) were compared with those suffering high falls (> or = 2 m), motor vehicle
      crashes, assault, sports injuries, and a group with unclassified injuries.
      Probability of survival was estimated using TRISS, and its performance in
      different types of injury was assessed using measures of discrimination and
      calibration. The influence of coexistent medical conditions on mortality and
      length of stay was investigated using logistic regression. RESULTS: Low falls
      accounted for 45.5% of all admissions, and 43.9% of the total bed days. The low
      fall group was older (mean age, 61.6 years), and predominantly female (62.5%) in
      contrast to the other groups (both p < 0.001). There were fewer severely injured
      patients than in all of the other groups except sports injuries. The area under
      the receiver operating characteristic curve for TRISS applied to low falls
      (0.874) was less than that for high falls (0.969), motor vehicle crashes (0.973),
      assaults (0.960), sports (1.000), and unclassified injuries (0.965). Also, the
      calibration of the TRISS model was poor for patients with low falls. A logistic
      regression model derived from a training set of 5,000 patients gave slightly
      improved discrimination and markedly improved calibration when compared with
      TRISS. Although there was a strong relationship between the number of coexistent
      medical conditions and the risk of dying after a low fall, including data on
      comorbidities in a predictive model did not improve performance. Prolonged stay
      (defined as greater than the 90th centile, 23 days) was more likely in women (p <
      0.005), or with advanced age (p < 0.001) or low initial calculated probability of
      survival (p < 0.001). Cardiovascular and central nervous system diseases and
      diabetes were associated with longer hospital stay (all p < 0.001). A logistic
      regression model using TRISS variables and comorbidity data gave poor prediction
      of prolonged stay. There was considerable variation in the length of stay between
      institutions. CONCLUSION: Patients with low falls make considerable demands on a
      system of trauma care. TRISS methodology performs less well in this group than
      with other types of injury. Chronic medical conditions are associated with
      increased mortality and more prolonged stay after a low fall. Between
      institutional variation in length of stay was considerable and this, along with
      the poor performance of predictive models derived from routinely collected
      clinical data, make it unlikely that length of stay could be used as a measure of
      institutional performance. More robust audit measures for patients with low falls
      are required.

PMID- 11586166
TI  - Beyond the major trauma outcome study: benchmarking performance using a national
      contemporary, population-based trauma registry.

PMID- 11586167
TI  - Local instillation of Staphylococcus aureus peptidoglycan at operation prevents
      wound healing impairment after trauma.
AB  - BACKGROUND: Considerable experimental evidence and limited clinical evidence
      indicate that wound healing is impaired after trauma. Because Staphylococcus
      aureus peptidoglycan (SaPG) accelerates healing in normal rats and prevents wound
      healing impairment induced by glucocorticoids, cyclophosphamide, and
      streptozotocin-diabetes, we hypothesized that SaPG would prevent the impaired
      wound healing after trauma. METHODS: In each of two experiments, 18 Sprague
      Dawley male rats were divided into two groups, nine rats each, paired by weight;
      one group received unilateral comminuted femoral fracture and wounding (two
      dorsal skin incisions and six subcutaneous polyvinyl alcohol [PVA] sponges), and
      the other group was only wounded. The incision and PVA sponges on one side were
      inoculated at operation with saline (200 microL/incision, 50 microL/sponge) and
      on the other side with SaPG in saline (860 microg of SaPG per centimeter of
      incision, 0.5 mg of SaPG per sponge). Rats ate chow and drank tap water ad
      libitum and were killed 7 days postoperatively. RESULTS: In both experiments, the
      wound breaking strength (WBS) of saline-inoculated incisions was significantly
      lower in rats with femoral fracture; histologically, reparative granulation
      tissue was looser and less prominent. WBS of SaPG-inoculated incisions in rats
      with and without femoral fracture was significantly higher than that of saline
      inoculated incisions and, histologically, reparative tissue was more prevalent,
      more closely packed, and more mature. WBS of SaPG-inoculated incisions in rats
      with femoral fracture was similar to that of saline-inoculated incisions in rats
      without femoral fracture. Reparative tissue hydroxyproline and histologic
      findings of saline-inoculated PVA sponge reparative tissue were similar in all
      rats, as were the increases induced by SaPG inoculation. CONCLUSION: Wound
      breaking strength and histologic findings of skin incisions (impaired in rats
      with unilateral femoral fracture) are more sensitive to the adverse effects of
      trauma than accumulation of PVA sponge reparative tissue. A single inoculation of
      SaPG at operation increased wound incision healing in rats both without and with
      femoral fracture and notably prevented the impaired healing in rats with femoral
      fracture.

PMID- 11586168
TI  - Fatty infiltration of the liver in severely burned pediatric patients: autopsy
      findings and clinical implications.
AB  - BACKGROUND: Trauma induces hypermetabolic responses that are characterized by the
      mobilization of all available substrates. The marked increase of peripheral
      lipolysis after a burn can lead to the development of fatty liver, which has been
      associated with immunodepression and increased mortality. METHODS: All autopsies
      of pediatric burn patients between January 1988 and January 1998 were reviewed.
      Patient demographics, hospital course, cause of death, and hepatic and septic
      macroscopic and microscopic findings were recorded. RESULTS: Thirty-seven
      pediatric patients (4 +/- 1 years old) were included in the study. The mean burn
      size was 69% +/- 5% total body surface area burned. Eighty percent of the
      patients presented with fatty infiltration of the liver. Liver weight/body weight
      ratio was 77 +/- 5 gm/kg, representing 2.1 times the liver weight of age- and sex
      matched controls (p < 0.001). Patients with severe fatty infiltration of the
      liver had a higher incidence of sepsis (p < 0.001). CONCLUSION: Fatty
      infiltration of the liver is a common condition in fatal burns. Severe fatty
      infiltration of the liver is associated with an increased incidence of sepsis,
      although a causative effect could not be found. It is notable that fatty
      infiltration of the liver occurred in the complete absence of parenteral
      nutrition.

PMID- 11586169
TI  - Development of a brief version of the Burn Specific Health Scale (BSHS-B).
AB  - BACKGROUND: The Burn Specific Health Scale (BSHS) is an outcome scale designed
      specifically for burn patients. The scale has been abbreviated (BSHS-A) and
      revised (BSHS-R). We used a factor analytic approach to further improve the scale
      for clinical use. METHODS: Two hundred forty-eight of 350 former patients (70.9%)
      treated at the Uppsala Burn Unit between 1980 and 1995 responded to 94 questions
      from previous versions of the BSHS. RESULTS: Principal components factor analyses
      were used to derive an instrument with 40 items called the Burn Specific Health
      Scale-Brief (BSHS-B), resulting in nine well-defined domains with
      intercorrelations ranging from 0.11 to 0.56, and Chronbach's factor alphas
      ranging from 0.75 to 0.93. The domains describe function with respect to Heat
      Sensitivity, Affect, Hand Function, Treatment Regimens, Work, Sexuality,
      Interpersonal Relationships, Simple Abilities, and Body Image. CONCLUSION: The
      BSHS-B is a valid but shorter alternative to the previously described BSHS-A.
      Important domains of postburn distress are captured better in the BSHS-B than in
      the BSHS-R.

PMID- 11586170
TI  - Priorities for improving hospital-based trauma care in an African city.
AB  - BACKGROUND: This study sought to identify potential cost-effective methods to
      improve trauma care in hospitals in the developing world. METHODS: Injured
      patients admitted to an urban hospital in Ghana over a 1-year period were
      analyzed prospectively for mechanism of injury, mode of transport to the
      hospital, injury severity, region of principal injury, operations performed, and
      mortality. In addition, time from injury until arrival at the hospital and time
      from arrival at the hospital until emergency surgery were evaluated. RESULTS:
      Mortality was 9.4%. Most deaths (65%) occurred within 24 hours of admission.
      Sixty percent of emergency operations were performed over 6 hours after arrival.
      Tube thoracostomy was performed on only 13 patients (0.6%). Only 58% of patients
      received intravenous crystalloid and only 3.6% received 1 or more units of blood.
      CONCLUSION: We identified several specific interventions as potential low-cost
      measures to improve hospital-based trauma care in this setting, including shorter
      times to emergency surgery and improvements in initial resuscitation. In addition
      to addressing each of these aspects of trauma care individually, quality
      improvement programs may represent a feasible and sustainable method to improve
      trauma care in hospitals in the developing world.

PMID- 11586171
TI  - Old age as a criterion for trauma team activation.
AB  - BACKGROUND: Elderly trauma patients have been shown to have a worse prognosis
      than young patients. Age alone is not a criterion for trauma team activation
      (TTA). In the present study, we evaluated the role of age > or = 70 years as a
      criterion for TTA. METHODS: The present study was a trauma registry study that
      included injured patients 70 years of age or older. Patients who died in
      hospital, were admitted to the intensive care unit (ICU) within 24 hours, or had
      a non-orthopedic operation were assumed to benefit from TTA. RESULTS: During a
      7.5-year period, 883 elderly (> or = 70 years) trauma patients meeting trauma
      center criteria were admitted to our center. Overall, 223 patients (25%) met at
      least one of the standard TTA criteria. The mortality in this group was 50%, the
      ICU admission rate was 39%, and a non-orthopedic operation was required in 35%.
      The remaining 660 patients (75%) did not meet standard TTA criteria. The
      mortality was 16%, the need for ICU admission was 24%, and non-orthopedic
      operations were required in 19%. Sixty-three percent of patients with severe
      injuries (Injury Severity Score > 15) and 25% of patients with critical injuries
      (Injury Severity Score > 30) did not have any of the standard hemodynamic
      criteria for TTA. CONCLUSION: Elderly trauma patients have a high mortality, even
      with fairly minor or moderately severe injuries. A significant number of elderly
      patients with severe injuries do not meet the standard criteria for TTA. It is
      suggested that age > or = 70 years alone should be a criterion for TTA.

PMID- 11586172
TI  - Epidemiology of unintentional adult injury in a rural population.
AB  - BACKGROUND: The purpose of this study was to describe the frequency,
      characteristics, and risk factors of unintentional adult injury in a rural
      population. METHODS: We interviewed 1,644 adults representing an all-rural county
      in Iowa. Analyses used bivariate and multivariable logistic regression. RESULTS:
      Participants' mean age was 53 years, and 54% were women. Twenty-three percent (n
      = 380) of participants reported an injury during the past 12 months, of which
      four fifths were treated. Overexertion (25%) and falls (22%) caused nearly half
      the injuries. Women with high levels of depression symptoms had 1.57 times (95%
      confidence interval, 1.05-2.33) the prevalence of injury occurrence as did women
      with low levels of depression symptoms. Men with a CAGE score of 2 or more had
      between 0.98 and 2.56 times (according to the range of values of the relevant
      odds ratio 95% confidence interval) the prevalence of injury episode of men
      without this exposure. CONCLUSION: The association of injury occurrence with
      alcohol problems is consistent with prior research, but the increased prevalence
      of injury associated with high levels of symptoms of depression requires further
      study and explanation.

PMID- 11586173
TI  - Pain relief in major trauma patients: an Israeli perspective.
AB  - BACKGROUND: The pain of major trauma patients remains often unrelieved while in
      the emergency department. Our objective was to examine pain management in several
      trauma units, and to evaluate the impact of implementation of a trauma pain
      management protocol. METHODS: Current status was evaluated from questionnaires
      filled by trauma unit personnel of nine medical centers. In one, a pain
      management protocol was introduced. Staff and patients evaluated pain management
      before and after the protocol was instituted. RESULTS: About 80% of staff
      respondents from various centers were not aware of guidelines for pain management
      in trauma. The belief that pain assists diagnosis was the main reason (78.6%) for
      withholding analgesia. Large variability existed on what contraindicates
      analgesia, with the majority withholding analgesia in abdominal and multiple
      injuries. When administered, analgesia was delayed, and most commonly
      intramuscular meperidine was given. After the protocol's implementation, the
      personnel's awareness of analgesia increased, and consequently it was
      administered earlier and to more patients, mostly as intravenous morphine.
      Patients appreciated the timely analgesia (38% after vs. 14% before, p = 0.01),
      with fewer receiving none. Analgesia was considered beneficial by more patients
      (70% after vs. 23% before, p < 0.001), and enhanced cooperativity with personnel
      (p < 0.001). This was reflected in increased overall satisfaction with pain
      relief during the entire hospitalization. CONCLUSION: The importance of pain
      management protocols in major trauma was demonstrated by the response of
      personnel and patients.

PMID- 11586174
TI  - Open anterior dislocation of the hip in a child.

PMID- 11586176
TI  - Delayed arteriovenous fistula and pseudoaneurysm after an open tibial fracture
      successfully managed with selective angiographic embolization.

PMID- 11586175
TI  - Delayed arterial bleed 10 days after pelvic ring injury resulting in vaginal wall
      laceration.

PMID- 11586177
TI  - Tricortical bone-block grafting for comminuted supracondylar and intercondylar
      fracture of the elbow in an elderly woman: case report.

PMID- 11586178
TI  - Isolated dislocation of the pisiform: an unusual injury during a cartwheel
      maneuver.

PMID- 11586179
TI  - Bilateral subperiosteal orbital hemorrhages after a compressive thoracoabdominal
      injury.

PMID- 11586180
TI  - Coil embolization of rectus sheath hemorrhage.

PMID- 11586181
TI  - Great vessel injury after hockey-related trauma: two case reports and a
      literature review.

PMID- 11586182
TI  - A review of the adrenal cortex and severe inflammation: quest of the
      "eucorticoid" state.

PMID- 11586183
TI  - Inferior vena cava syndrome resulting from a posttraumatic intrahepatic biloma.

PMID- 11586184
TI  - Carotid and vertebral artery dissection due to deceleration injury in a motor
      vehicle crash.

PMID- 11586185
TI  - Re: mechanism of healing following the Snodgrass repair.

PMID- 11586186
TI  - Re: urinary continence and pathological outcome after bladder neck preservation
      during radical retropubic prostatectomy: a randomized prospective trial.

PMID- 11586187
TI  - Re: the treatment of post-urethrotomy incontinence in pediatric and adolescent
      females.

PMID- 11586189
TI  - The changing natural history of renal cell carcinoma.
AB  - PURPOSE: Our understanding of the natural history of renal cell carcinoma, the
      role of nephrectomy, the benefits of immunotherapy and the possibilities of new
      technologies are evolving and being integrated with advances in classification
      and staging. We reviewed the relevant literature to clarify these pertinent
      questions and provide a current review of the changes in the epidemiology,
      treatment and prognosis of patients with renal cell carcinoma. MATERIALS AND
      METHODS: We comprehensively reviewed the peer reviewed literature on the current
      management of and results of treatment for renal cell carcinoma. RESULTS: The
      incidence of and mortality from renal cell carcinoma have continuously increased
      during the last 50 years. Despite this increase in the number of new patients and
      consequently the number of deaths yearly the percent of those surviving for 5
      years has notably improved. Factors related to improved survival include advances
      in renal imaging, earlier diagnosis, improved staging, better understanding of
      prognostic indicators, refinement in surgical technique and the introduction of
      immunotherapy approaches for advanced disease. CONCLUSIONS: Currently patients
      with localized and metastatic renal cell carcinoma have had improvements in
      outlook and the therapeutic options available have expanded.

PMID- 11586190
TI  - Smoking and erectile dysfunction: evidence based analysis.
AB  - PURPOSE: We examined available evidence concerning the role of smoking in the
      development of erectile dysfunction. This task involved a complete review of the
      smoking literature as it pertained to erectile dysfunction and select endothelial
      diseases. MATERIALS AND METHODS: We comprehensively reviewed the literature,
      including PubMed and recent abstract proceedings from national meetings relevant
      to smoking, erectile dysfunction and endothelial diseases. The quality of the
      evidence was assessed by methods used to develop clinical practice guidelines.
      Our review involved an objective evaluation of the basic science literature and
      clinical studies. When necessary, we examined studies of endothelial diseases
      other than erectile dysfunction because of obvious gaps in the literature.
      RESULTS: There are strong parallels and shared risks among smoking, coronary
      artery disease, atherosclerosis and erectile dysfunction. Clinical and basic
      science studies provide strong indirect evidence that smoking may affect penile
      erection by the impairment of endothelium dependent smooth muscle relaxation. The
      association of erectile dysfunction with risk factors such as coronary artery
      disease and hypertension appears to be amplified by cigarette smoking. Smoking
      may increase the likelihood of moderate or complete erectile dysfunction 2-fold.
      The prevalence of erectile dysfunction in former smokers was no different from
      that in individuals who had never smoked, implying that smoking cessation may
      decrease the risk of erectile dysfunction. Case studies and retrospective series
      have shown an association of smoking with erectile dysfunction. CONCLUSIONS:
      Available evidence on the association of smoking with erectile dysfunction is not
      complete insofar as association linking factors are concerned. However, the
      evidence of such an association is likely due to the consistency of the
      relationship of smoking and endothelial disease, and the strength of the
      association of erectile dysfunction with other endothelial diseases.

PMID- 11586191
TI  - Mycobacterial cell wall extract for treatment of carcinoma in situ of the
      bladder.
AB  - PURPOSE: Bacillus Calmette-Guerin (BCG) established immunotherapy as an effective
      modality for carcinoma in situ of the bladder and remains the most effective
      agent for treatment. However, as a live organism it has the potential for
      undesirable side effects and toxicity. This result has led to the search for
      other active and safer biological response modifiers. We investigated the
      efficacy of a mycobacterial cell wall extract (MCWE) from Mycobacterium phlei,
      which does not contain live bacteria, for management of carcinoma in situ of the
      bladder in humans. MATERIALS AND METHODS: The requirement for an emulsified
      preparation was investigated with photon correlation spectroscopy to determine
      the stability of the bacterial fragments. A total of 61 patients with
      histologically documented carcinoma in situ completed the study. Cell wall
      extract from M. phlei suspended in oil droplets to form an emulsion were
      instilled into the bladder at a dose of 4 mg. once weekly for 6 weeks and then
      monthly for 1 year. Response assessment was performed at 3-month intervals.
      Complete response to treatment indicated the absence of endoscopic and
      histological evidence of carcinoma in situ. Partial responders were those cases
      in which cystoscopy and biopsies were negative but cytology was suspicious for
      malignant cells. All other cases were considered failures. RESULTS: The need for
      an emulsified suspension of the cell wall extract was confirmed by the
      demonstration that the cell wall extract alone in urine aggregated, whereas the
      MCWE emulsion had remained stable. Kaplan-Meier estimates showed negative
      cystoscopy and biopsies in 62.5% at 12, 49.3% at 24 and 41.1% of patients at 60
      weeks after therapy. After this point the number of responders had remained
      stable. Excellent tolerance with minimal toxicity was observed. CONCLUSIONS: Our
      study demonstrates clinical activity of low doses of MCWE against human bladder
      cancer. The results observed at the dosage used in our trial are less than those
      observed with live BCG. However, MCWE has a better toxicity profile and can be
      instilled in the presence of a disrupted urothelium. It also appears to exhibit
      activity in patients in whom BCG has failed.

PMID- 11586192
TI  - Clinical and endocrinological features of adrenocorticotropic hormone-
      independent bilateral macronodular adrenocortical hyperplasia.
AB  - PURPOSE: We report clinical findings in 5 patients with adrenocorticotropic
      hormone independent bilateral macronodular adrenocortical hyperplasia. MATERIALS
      AND METHODS: In 4 males and 1 female 32 to 61 years old (median age 50) we
      evaluated clinical symptoms, endocrinological and radiological characteristics,
      treatment modality and postoperative clinical course. RESULTS: All cases
      presented with some features of Cushing's syndrome. Endocrinological examination
      revealed autonomous adrenal cortisol production with suppressed
      adrenocorticotropic hormone and a loss in the diurnal circadian rhythm of plasma
      cortisol. Abdominal computerized tomography showed bilateral enlargement of the
      adrenal glands with multiple nodules. 131Iodine labeled adosterol scintigraphy
      demonstrated remarkable bilateral uptake by the adrenal glands. The pituitary
      gland appeared normal on magnetic resonance imaging. Open unilateral complete
      adrenalectomy and contralateral partial adrenalectomy were performed in patient
      1, open bilateral complete adrenalectomy was done in patients 2 and 3, and 2 and
      1-stage laparoscopic bilateral complete adrenalectomy was performed in patients 4
      and 5. Single removed adrenal glands weighed 32 to 108 gm. (median 60). The
      histological diagnosis was macronodular adrenocortical hyperplasia in all cases.
      Postoperative followup was 3 to 90 months. Clinical symptoms of Cushing's
      syndrome disappeared or improved after surgery in all cases. CONCLUSIONS:
      Although adrenocorticotropic hormone independent bilateral macronodular
      adrenocortical hyperplasia is a rare form of Cushing's syndrome, physicians are
      advised to consider it when diagnosing and treating cases of Cushing's syndrome
      with enlarged bilateral adrenal glands. Bilateral complete adrenalectomy is
      currently recommended as the treatment of choice.

PMID- 11586193
TI  - Decreased predominance of papG class II allele in Escherichia coli strains
      isolated from adults with acute pyelonephritis and urinary tract abnormalities.
AB  - PURPOSE: We compared the genotypes of fimbriae or adhesions of Escherichia coli
      causing acute pyelonephritis in adults with and without urinary tract
      abnormalities. MATERIALS AND METHODS: We studied a total of 92 E. coli strains
      isolated from 54 patients with acute pyelonephritis and a normal urinary tract,
      and 38 with urinary tract abnormalities. Of those with urinary tract
      abnormalities 13 with moderate to severe hydronephrosis were also considered a
      separate group for the purpose of analysis. The genes of 7 known fimbriae or
      adhesins of E. coli were detected by the polymerase chain reaction, including the
      papG class I to III alleles (PapG adhesins of P-fimbriae), sfa/foc (S-/F1C
      fimbriae), fimH (type 1 fimbriae), and afa (afimbrial adhesin). Virulence genes
      associated with APN were identified by comparing the prevalence of each of these
      7 genes in E. coli strains from 54 patients with acute pyelonephritis with a
      normal urinary tract to the prevalence in the strains from 37 patients with acute
      cystitis using univariate and multivariate analysis. Differences in the
      prevalence of the genes associated with acute pyelonephritis and the incidence of
      underlying illness were then compared in the 3 acute pyelonephritis groups.
      RESULTS: On univariate and multivariate analysis the papG class II allele was the
      only virulence gene associated with acute pyelonephritis (p <0.0001 and 0.001,
      respectively). No significant difference was noted in the prevalence of
      underlying medical disease in the 3 acute pyelonephritis groups. The papG class
      II allele was significantly less predominant in E. coli strains isolated from
      acute pyelonephritis cases with versus without urinary tract abnormalities (76%
      versus 93%, p = 0.03). The incidence of the papG class II allele in patients with
      urinary tract abnormalities and moderate to severe hydronephrosis was less than
      in those without urinary tract abnormalities (69% versus 93%, p = 0.04).
      CONCLUSIONS: Our results imply that the papG class II allele has an important
      role in E. coli infection in patients with acute pyelonephritis and a normal
      urinary tract, while urinary tract abnormalities and/or obstruction may permit
      ascending infection of E. coli strains with lower adhesive ability.

PMID- 11586194
TI  - Indication, surgical technique and outcome of orthotopic renal transplantation.
AB  - PURPOSE: We review the indication, surgical technique and outcome of orthotopic
      renal transplantation. MATERIALS AND METHODS: The medical records of 1,000
      patients who underwent renal transplantation at our institution between August
      24, 1993 and August 1, 2000, as well as orthotopic renal transplantation were
      reviewed. RESULTS: Orthotopic renal transplantation was performed in 4 males and
      1 female with severe iliac atherosclerosis or retained bilateral iliac fossa
      kidney transplant. Mean patient age was 56 years. There were 2 patients who
      received kidneys from living related donors, and 3 underwent cadaveric renal
      transplantation. Left orthotopic renal transplantation was successful in 4 cases,
      and 1 was converted to iliac fossa renal transplant because of a pulseless
      splenic artery and renal artery thrombosis after native renal endarterectomy.
      Orthotopic renal revascularization was done with splenic artery in 2, native
      renal artery in 2 and left renal vein in all 4 patients. Urinary tract
      reconstruction was performed with stented (2) or nonstented (2)
      ureteroureterostomy. Antibody induction, purine antagonists, calcineurin
      inhibitors and glucocorticoids were used for immunosuppression. Mean preoperative
      and 1-month postoperative serum creatinine was 7.9 and 1.3 mg./dl., respectively.
      Patient and graft survival was 100% during followup, which ranged from 6 months
      to 5 years. CONCLUSIONS: Despite the technical challenges, orthotopic renal
      transplantation in patients with unsuitable pelvic vessels can result in
      excellent patient and graft survival.

PMID- 11586195
TI  - Ureteral stenting after ureteroscopy for distal ureteral calculi: a multi
      institutional prospective randomized controlled study assessing pain, outcomes
      and complications.
AB  - PURPOSE: We compare postoperative pain, stone-free rates and complications after
      ureteroscopic treatment of distal ureteral calculi with or without the use of
      ureteral stents. MATERIALS AND METHODS: A total of 113 patients with distal
      ureteral calculi amenable to ureteroscopic treatment were prospectively
      randomized into stented (53) and unstented (60) groups. Stones were managed with
      semirigid ureteroscopes with or without distal ureteral dilation and/or
      intracorporeal lithotripsy. Preoperative and postoperative pain questionnaires
      were obtained from each patient. Patients with stents had them removed 3 to 10
      days postoperatively. Radiographic followup was performed postoperatively to
      assess stone-free rates and evidence of obstruction. RESULTS: Six patients
      randomized to the unstented group were withdrawn from the study after significant
      intraoperative ureteral trauma was recognized, including 3 ureteral perforations,
      that required ureteral stent placement, leaving 53 with stents and 54 without for
      analysis. Patients with stents had statistically significantly more postoperative
      flank pain (p = 0.005), bladder pain (p <0.001), urinary symptoms (p = 0.002),
      overall pain (p <0.001) and total narcotic use (p <0.001) compared to the
      unstented group. Intraoperative ureteral dilation or intracorporeal lithotripsy
      did not statistically significantly affect postoperative pain or narcotic use in
      either group (p >0.05 in all cases). Overall mean stone size in our study was 6.6
      mm. There were 4 (7.4%) patients without stents who required postoperative
      readmission to the hospital secondary to flank pain. All patients (85%) who
      underwent imaging postoperatively were without evidence of obstruction or
      ureteral stricture on followup imaging (mean followup plus or minus standard
      deviation 1.8 +/- 1.5 months), and the stone-free rate was 99.1%. CONCLUSIONS:
      Uncomplicated ureteroscopy for distal ureteral calculi with or without
      intraoperative ureteral dilation can safely be performed without placement of a
      ureteral stent. Patients without stents had significantly less pain, fewer
      urinary symptoms and decreased narcotic use postoperatively.

PMID- 11586196
TI  - The impact of intense laparoscopic skills training on the operative performance
      of urology residents.
AB  - PURPOSE: As laparoscopy has become more commonplace in urology, increased
      emphasis has been placed on laparoscopic education. We assessed the impact of
      laparoscopic skills training on the operative performance of urological surgeons
      inexperienced with laparoscopy. MATERIALS AND METHODS: Urology residents were
      prospectively randomized to undergo laparoscopic skills training (6) or no
      training (6). Baseline assessment of operative performance (scale 0 to 35) during
      porcine laparoscopic nephrectomy was completed by all subjects. Cumulative time
      to complete laparoscopic tasks using an inanimate trainer was also recorded. The
      skills training group then practiced inanimate trainer tasks for 30 minutes daily
      for 10 days. The 2 groups then repeated the timed inanimate trainer tasks and
      underwent repeat assessment of the ability to perform porcine laparoscopic
      nephrectomy. RESULTS: At baseline no statistical difference was noted in
      laparoscopic experience, inanimate trainer time or overall operative assessment
      in the 2 groups. In the skills training group mean cumulative time to complete
      inanimate trainer tasks decreased from 341 to 176 seconds (p = 0.003), while in
      the control group it decreased from 365 to 301 (p = 0.15). Operative assessment
      improved from initial to repeat porcine laparoscopic nephrectomy regardless of
      the trained versus control randomization grouping (22.0 to 27.8, p = 0.0008 and
      20.8 to 26.5, p = 0.00007, respectively). CONCLUSIONS: In vivo experience enables
      urological surgeons inexperienced with laparoscopy to improve significantly in
      all aspects of complex laparoscopic procedures. In this pilot study the magnitude
      of improvement was independent of additional training in laparoscopic skills.
      Educational curriculum should include in vivo practice in addition to skills
      training.

PMID- 11586197
TI  - Early removal of the catheter after laparoscopic radical prostatectomy.
AB  - PURPOSE: We prospectively tested the safety of routine removal of the catheter as
      early as 2 to 4 days after laparoscopic radical prostatectomy. MATERIALS AND
      METHODS: Between March 1998 and March 2001, 228 patients underwent laparoscopic
      radical prostatectomy for clinically organ confined prostate cancer. The last 113
      consecutive patients were included in a prospective study according to
      gravitational cystography performed 2 to 4 days postoperatively. If no leak was
      seen the catheter was removed. If a leak was apparent the catheter was left
      indwelling for another 6 days and cystography was repeated. RESULTS: Cystography
      2 to 4 days postoperatively showed an anastomosis without a leak in 96 (84.9%)
      patients who subsequently had the catheters removed. There were 28 patients who
      had the catheter removed on postoperative day 2, 28 day 3 and 40 day 4. In 17
      (15.1%) patients an anastomotic leak was observed, and the catheter was not
      removed at that time. Of the 96 patients in whom the catheter was removed early
      10 (10.4%) had urinary retention that necessitated re-catheterization. This
      procedure was performed without the need for cystoscopy. After the catheter was
      removed all patients were able to void 24 hours later. Median followup was 7
      months (range 1 to 15) and showed continence rates greater than 93%. No
      anastomotic stricture, pelvic abscess or urinoma developed in any patient.
      CONCLUSIONS: Patients who undergo laparoscopic radical prostatectomy can have the
      catheter safely removed 2 to 4 days postoperatively without a higher risk of
      incontinence, stricture or leak related problems.

PMID- 11586198
TI  - Quantification of 5-aminolevulinic acid induced fluorescence improves the
      specificity of bladder cancer detection.
AB  - PURPOSE: 5-Aminolevulinic acid induced fluorescence endoscopy has outstanding
      sensitivity for detecting early stage bladder cancer. Nevertheless, a third of
      the lesions that show specific fluorescence are histologically benign. We
      decreased the false-positive rate of 5-aminolevulinic acid induced fluorescence
      endoscopy by incorporating protoporphyrin IX fluorescence quantification into the
      standard cystoscopy procedure. MATERIALS AND METHODS: In 25 cases (53 biopsies)
      of a history of or suspicion for bladder cancer 5-aminolevulinic acid induced
      fluorescence endoscopy and fluorescence image quantification were performed. For
      fluorescence image quantification images obtained with a target integrating color
      charge-coupled device camera were digitized and stored in a personal computer.
      Red-to-blue ratios were calculated from fluorescence positive lesions and results
      were correlated with hematoxylin and eosin histology. RESULTS: Malignant
      fluorescence positive lesions showed significantly stronger fluorescence
      intensity than fluorescing lesions with benign histology. A threshold was
      established that decreased the false-positive rate by 30% without affecting
      sensitivity. CONCLUSIONS: Fluorescence image quantification is a new endoscopic
      method for objectively selecting multicolor fluorescence bladder lesion images
      for biopsy. It has the potential of eliminating human error by different surgeons
      with variable experience in fluorescence endoscopy.

PMID- 11586199
TI  - Laser therapy for carcinoma in situ of the penis.
AB  - PURPOSE: Carcinoma in situ of the penis, also referred to as Bowen's disease or
      erythroplasia of Queyrat, may lead to invasive squamous cell carcinoma. We
      assessed the results of laser therapy for carcinoma in situ of the penis.
      MATERIALS AND METHODS: From 1986 to 2000 we treated 19 patients with carcinoma in
      situ of the penis with the neodymium:YAG or carbon dioxide laser. Treatment was
      assessed retrospectively. No patient was lost to followup. RESULTS: No
      complications developed and cosmesis was excellent. After 2 to 4 months 3
      patients (16%) received repeat treatment because of incomplete disappearance of
      the lesion. Mean followup was 32 months. True carcinoma in situ recurrent in 5
      patients (26%) at an average followup of 25 months (range 6 to 75), while 1 had
      infiltrating carcinoma. All patients with carcinoma in situ underwent repeat
      laser treatment. CONCLUSIONS: In our experience laser therapy is appropriate
      initial treatment for carcinoma in situ of the penis with excellent cosmetic and
      functional results. This therapy is also suited for recurrence without the need
      for more mutilating therapy. However, the high incidence of recurrence indicates
      the need for careful followup and patient self-examination.

PMID- 11586200
TI  - The use of neural networks and logistic regression analysis for predicting
      pathological stage in men undergoing radical prostatectomy: a population based
      study.
AB  - PURPOSE: Clinical under staging occurs in 40% to 60% of patients who undergo
      radical prostatectomy for prostate cancer. To decrease under staging several
      methods of predicting pathological stage preoperatively have been developed based
      on statistical logistic regression analysis and neural networks. To our knowledge
      none has been validated in our homogeneous regional patient population to date.
      We created logistic regression and neural network models, and implemented and
      adapted them into our practice. We also compared the 2 methods to determine their
      value and practicality in daily clinical practice. We present the results of our
      novel approach for predicting pathological staging of prostate adenocarcinoma.
      MATERIALS AND METHODS: Between 1986 and 1999, 600 white men from the Aragon
      region of Spain underwent surgery for prostate cancer; of whom 468 were selected
      for study. Predictive study variables included patient age, clinical stage,
      biopsy Gleason score and preoperative prostate specific antigen (PSA). The
      predicted result included in analysis was organ confined or nonorgan confined
      disease. Data were analyzed by multivariate logistic regression and a supervised
      neural network (multilayer perceptron and radial basis function). Results were
      compared by comparing the areas under the receiver operating characteristics
      curves. RESULTS: We generated 5 logistic regression models. The model created
      with clinical staging, Gleason biopsy score and PSA distributed in 5 categories
      (p <0.001) with an area under the receiver operating characteristics curve of
      0.840 proved to be most predictive of pathological stage. Similarly of the 6
      neural network models evaluated the radial basis function model, which included
      age, clinical stage, Gleason biopsy score and preoperative PSA distributed in 5
      categories with an area under the curve of 0.882, proved the most predictive but
      not superior to the logistic regression model. The difference in the area under
      the curves in the 2 chosen models was 0.042 (p = 0.1). CONCLUSIONS: It is
      possible to generate useful predictive models of organ confined disease using
      logistic regression or neural networks with high indexes of clinical and
      statistical validity. However, using these variables neural networks did not
      prove to be better than logistic regression analysis. Therefore, better
      predictive variables must be identified, preferably nonlinear characteristics
      with respect to the probability of organ confined tumor, to generate better
      predictive models using neural networks.

PMID- 11586201
TI  - Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4:
      when should we stop?
AB  - PURPOSE: We evaluated biochemical parameters and pathological features, as well
      as biopsy related morbidity of prostate cancer detected on biopsies 2, 3 and 4 in
      men with total serum prostate specific antigen (PSA) between 4 and 10 ng./ml.
      These features were compared to those detected on prostate biopsy 1. MATERIALS
      AND METHODS: In this prospective European Prostate Cancer Detection study 1,051
      men with total PSA between 4 and 10 ng./ml. underwent transrectal ultrasound
      guided sextant biopsy and 2 additional transition zone biopsies. All patients in
      whom biopsy samples were negative for prostate cancer underwent biopsy 2 after 6
      weeks. If also negative, biopsies 3 and even 4 were performed at 8-week
      intervals. Those patients with clinically localized cancer underwent radical
      prostatectomy. Pathological and clinical features of patients diagnosed with
      cancer on either biopsy 1 or 2 and clinically organ confined disease who agreed
      to undergo radical prostatectomy were compared. RESULTS: Cancer detection rates
      on biopsies 1, 2, 3 and 4 were 22% (231 of 1,051), 10% (83 of 820), 5% (36 of
      737) and 4% (4 of 94), respectively. Overall, of the patients with clinically
      localized disease, which was 67% of cancers detected, 86% underwent radical
      prostatectomy and 14% opted for watchful waiting or radiation therapy. Overall,
      58.0%, 60.9%, 86.3% and 100% of patients had organ confined disease on biopsies
      1, 2, 3 and 4, respectively. Despite statistically significant differences in
      regard to multifocality (p = 0.009) and cancer location (p = 0.001), including
      cancer on biopsy 2 showing a lower rate of multifocality and a more apico-dorsal
      location, there were no differences in regard to stage (p = 0.2), Gleason score
      (p = 0.3), percent Gleason grade 4/5 (p = 0.2), serum PSA and patient age between
      biopsies 1 and 2. However, cancer detected on biopsies 3 and 4 had a
      significantly lower Gleason score (p = 0.001 and 0.001), lower rate of grade 4/5
      (p = 0.02), and lower volume (p = 0.001 and 0.001) and stage (p = 0.001),
      respectively. CONCLUSIONS: Despite differences in location and multifocality,
      pathological and biochemical features of cancer detected on biopsies 1 and 2 were
      similar, suggesting comparable biological behaviors. Cancer detected on biopsies
      3 and 4 had a lower grade, stage and volume compared with that on biopsies 1 and
      2. Morbidity on biopsies 1 and 2 was similar, whereas biopsies 3 and 4 had a
      slightly higher complication rate. Therefore, biopsy 2 in all cases of a negative
      finding on biopsy 1 appears justified. However, biopsies 3 and 4 should only be
      obtained in select patients with a high suspicion of cancer and/or poor
      prognostic factors on biopsy 1 or 2.

PMID- 11586202
TI  - Efficacy of digital rectal examination after radiotherapy for prostate cancer.
AB  - PURPOSE: Digital rectal examination is widely performed for following patients
      with localized prostate cancer after definitive therapy. This examination has
      marginal efficacy for detecting initial prostate cancer and postoperative
      recurrence. To determine the efficacy of digital rectal examination in terms of
      new information provided after radiotherapy we analyzed the results of digital
      rectal examination in the followup of patients with prostate cancer after
      radiotherapy. MATERIALS AND METHODS: We performed a nonrandomized study in 235
      consecutive patients with prostate cancer followed at a large tertiary care
      military hospital between January 1, 1995 and December 31, 1999. All patients had
      been treated with prostate radiotherapy and had no evidence of metastatic disease
      at the first visit within that interval. Digital rectal examination was done at
      followup and the main outcome measure was new information provided by that
      examination. RESULTS: A total of 1,544 digital rectal examinations were performed
      in 1,627 visits. New information was provided by digital rectal examination in
      only 30% of 286 abnormal examinations, of which more than three-quarters were
      related to bleeding and would otherwise have been noted on routine examination by
      the primary care provider. All 8 persistent recurrent prostate nodules were noted
      in the context of increasing prostate specific antigen. CONCLUSIONS: Routine
      digital rectal examination in patients with prostate cancer after radiotherapy
      may be omitted from followup protocols.

PMID- 11586203
TI  - Dedifferentiation of prostate cancer grade with time in men followed expectantly
      for stage T1c disease.
AB  - PURPOSE: We assess whether the Gleason grade changes in men followed expectantly
      with clinical stage T1c prostate cancer. MATERIAL AND METHODS: We studied 70 men
      with stage T1c prostate cancer who underwent watchful waiting with repeat needle
      biopsy sampling to assess for progression. After the initial cancer diagnosis all
      men had at least 1 other biopsy demonstrating cancer. RESULTS: Of 70 cases 9
      (12.9%) showed a significant change in grade from Gleason scores 6 or less to 7
      or greater. The average followup of those patients without a change in grade was
      22 months and greater than those with a change in grade. There was no difference
      between the groups with and without changes in grade in regard to initial
      prostate specific antigen (PSA), percent-free PSA, or PSA density or velocity. Of
      9 cases there were 5 (56%) and 8 (89%) with grade change that occurred at 12 and
      15 months or less after initial biopsy, respectively. In contrast, only 1 of 24
      (4%) patients in whom last re-biopsy was performed 24 months or greater after the
      initial cancer diagnosis had a change in grade. Of the 21 men who underwent
      radical prostatectomy 5 (24%) had worsening of grade on the radical prostatectomy
      specimen compared to biopsy, with a mean interval of 18 months between the
      initial cancer diagnosis and prostatectomy. This prevalence of grade change is
      less than in our population that underwent prostatectomy within 1 to 3 months
      after biopsy. CONCLUSIONS: Because most grade changes occurred relatively soon
      after biopsy, it implies that tumor grade did not evolve but rather the higher
      grade component was not initially sampled. During a 1 1/2 to 2-year period after
      biopsy there is no evidence that prostate cancer grade worsens significantly. Men
      with prostate cancer need not feel concerned about waiting several months before
      undergoing surgery after biopsy. Furthermore, men undergoing watchful waiting can
      be reassured that there is little evidence that prostate cancer grade worsens
      during the short term.

PMID- 11586204
TI  - Prognostic factors for survival of patients with pathological Gleason score 7
      prostate cancer: differences in outcome between primary Gleason grades 3 and 4.
AB  - PURPOSE: We evaluated differences in clinical and pathological outcomes between
      Gleason 3 + 4 and 4 + 3 prostate cancer. MATERIALS AND METHODS: The radical
      prostatectomy whole mounted specimens from 263 men with pathological Gleason 7
      tumors were identified. Gleason 3 + 4 and 4 + 3 tumors were compared in regard to
      pathological variables and outcome. Significance of clinical and pathological
      data on progression-free survival was analyzed. RESULTS: Of the tumors 34% had a
      primary Gleason grade of 4, and were more likely than those with primary grade 3
      to have seminal vesicle involvement (34% versus 18%, p = 0.006), a higher
      pathological stage (pT3 55% versus 42%, N+ 13% versus 3%, 0.001), extraprostatic
      extension (58% versus 38%, 0.001) and higher median preoperative prostate
      specific antigen (PSA) (13.5 versus 9.0 ng./ml., respectively <0.001). Mean
      followup plus or minus standard deviation was 6.8 +/- 1.9 years. The overall 10
      year crude, cancer specific and progression-free survival rates were 83%, 99% and
      58%, respectively. Primary Gleason grade was significantly associated with
      progression-free (risk ratio 1.6, 95% confidence interval 1.08 to 2.5, p = 0.02)
      but not crude and cancer-specific survival. Univariately, primary Gleason grade 4
      was associated with progression-free survival, as were percent Gleason 4, seminal
      vesicle invasion, lymph node involvement, pT stage, margin status, DNA ploidy,
      preoperative PSA, cancer volume and extent of extraprostatic extension.
      Multivariately, only preoperative PSA (p <0.001), seminal vesicle invasion
      (<0.001) and DNA ploidy (0.002) were associated with progression-free survival.
      Primary Gleason grade and percent Gleason 4 were not identified as independently
      associated with progression-free survival. CONCLUSIONS: In patients with Gleason
      7 score prostate cancer primary Gleason grade 3 and 4 cancers are different in
      pathological parameters and prognosis. However, primary Gleason grade does not
      provide any additional information than other known prognostic factors, such as
      preoperative PSA, seminal vesicle invasion and DNA ploidy.

PMID- 11586205
TI  - Changes in collagen metabolism in prostate cancer: a host response that may alter
      progression.
AB  - PURPOSE: The interaction of cancer cells and the extracellular matrix is
      essential for cancer progression. However, little is known about the influence of
      cancer on the metabolism of collagen, which is the major constituent of the
      extracellular matrix. We studied changes in collagen metabolism in prostate
      cancer with increasing Gleason score and correlated them with clinical parameters
      and patient survival. MATERIALS AND METHODS: Collagen content and clinical
      parameters in 3 types of prostatic tissue were compared, including the foci of
      prostatic cancer, unaffected tissue from the same cancerous prostates and
      prostatic tissue from patients with no evidence of cancer. In addition, to assess
      collagen metabolism tissue obtained prospectively from 45 patients undergoing
      prostatic biopsy was assessed for collagen content, the type and extent of
      collagen cross-linking, serine proteinase, matrix metalloproteinase and the C
      terminal propeptide of type I collagen. RESULTS: With increasing Gleason sum of
      the cancer collagen content at the focus decreased, while that of surrounding
      unaffected tissue from the same prostate increased to levels significantly above
      that from controls with no cancer. Markers of collagen synthesis in the prostate
      biopsy material were significantly increased in the presence of prostate cancer.
      CONCLUSIONS: In prostate cancer there are changes in collagen metabolism not only
      in the cancer focus but also in nearby histologically benign prostatic tissue.
      These observed changes are related to the Gleason score of the tumor and may
      represent a host response. Collagen content in the surrounding unaffected tissue
      may be a predictor of patient survival.

PMID- 11586206
TI  - Conservative management of prostate cancer in the prostate specific antigen era:
      the incidence and time course of subsequent therapy.
AB  - PURPOSE: The long natural history of early stage prostate cancer is well
      recognized and a conservative approach to the treatment of elderly men is often
      encouraged. We assessed the ability of patients and physicians to adhere to a
      policy of watchful waiting in the prostate specific antigen (PSA) era. MATERIALS
      AND METHODS: We retrospectively reviewed the records of all 199 men with stages
      T1-2 prostate cancer and PSA less than 20 ng./ml. who in our practice elected
      watchful waiting. Median followup in the population overall was 3.4 years. We
      performed Kaplan-Meier actuarial analysis of overall and disease specific
      survival, and most pertinent survival free from therapy. A questionnaire was
      administered to record the attitude of patients who ultimately proceeded to
      treatment to determine how therapy was triggered. RESULTS: Median patient age was
      71 years and median PSA was 6.6 ng./ml. The tumor was impalpable in 52% of
      patients, Gleason sum was 6 or less in 80% and 11% used some form of herbal
      remedy or nutritional supplementation. Of the 37 men who died during observation,
      including 35 of co-morbid illness, only 6 underwent treatment. Overall survival
      at 5 and 7 years was 77% and 63% but disease specific survival was 98% and 98%,
      respectively. A total of 64 patients underwent treatment and actuarial freedom
      from treatment was 56% at 5 years, including 51% and 73% in those younger and
      older than 75 years at diagnosis. The likelihood of being alive and free from
      treatment was 43% at 5 years and 26% at 7. Of the 63 men treated 48 (76%)
      underwent radical therapy (brachytherapy in 17, external beam radiotherapy in 29
      and prostatectomy in 2), while only 24% received androgen deprivation. The median
      PSA increase from diagnosis to treatment in treated patients was 2.9 ng./ml., and
      it was 0.9 ng./ml. from diagnosis to the last followup in those not treated. Of
      the treated patients 81% believed that the physician had initiated therapy due to
      a PSA increase or a nodule. However, physicians recorded having advocated
      treatment in only 24% of cases. CONCLUSIONS: When patients do not die of co
      morbid illness, they are likely to proceed to therapy well within the first
      decade after diagnosis (57% by 5 years and 74% by 7). Therapy was usually
      definitive (radical) and triggered by slight, inevitable PSA increases. The
      patient perception was that the physicians initiated therapy in response to
      increasing PSA. However, the physicians more often perceived that treatment was
      initiated by patients. Therefore, watchful waiting in the PSA era often
      represents radical therapy delayed by a few years.

PMID- 11586207
TI  - Interstitial microwave thermal therapy for prostate cancer: method of treatment
      and results of a phase I/II trial.
AB  - PURPOSE: Interstitial microwave thermal therapy is experimental treatment for
      prostate cancer with the goal of curing disease, while causing fewer
      complications than standard treatment options. We present a method for delivering
      interstitial microwave thermal therapy using microwave radiating helical antennae
      inserted percutaneously under transrectal ultrasound guidance. We report the
      results of a trial of this method in 25 patients in whom primary external beam
      radiation therapy had previously failed. This patient group currently has limited
      curative options that are associated with a high complication rate. However,
      these recurrent tumors often remain localized to the prostate, and so they may be
      amenable to localized therapy. MATERIALS AND METHODS: Patients with proved
      prostatic adenocarcinoma were candidates for treatment when prostate specific
      antigen (PSA) was 15 ng./ml. or less and prostate volume was 50 cc. or less.
      Followup included PSA measurement, digital rectal examination, urinalysis, and
      documentation of adverse events at 4, 8, 12 and 24 weeks. Sextant biopsy was
      performed at week 24. The procedure involved the insertion of 5 antennae
      percutaneously through a modified brachytherapy template. The antenna arrangement
      was determined based on computer simulated predictions of temperature throughout
      the prostate. The prostate was dissected away from the rectum by an injection of
      sterile saline to provide a thermal barrier that protected the rectum from
      thermal damage. Temperatures were monitored using interstitial mapping thermistor
      probes that were also inserted through the template. A minimum peripheral target
      temperature of 55C but less than 70C was maintained for 15 to 20 minutes, while
      the urethra, rectum and hydrodissection space remained below 42C. The urethra and
      rectum were actively cooled in addition to hydrodissection. RESULTS: Peripheral
      target temperatures of 55C were achieved. The urethra and rectum remained at a
      safe temperature. The procedure, including setup and treatment, required
      approximately 2.5 hours of operating room time. At 24 weeks the PSA nadir was 0.5
      ng./ml. or less in 52% of patients and 0.51 to 4 ng./ml. was achieved in an
      additional 40%. The negative biopsy rate at 24 weeks was 64%, assuming that 3
      patients lost to followup would have had positive results. No major complications
      were observed and in most cases minor complications resolved within 3 months.
      CONCLUSIONS: Interstitial microwave thermal therapy for prostate cancer was
      developed to heat the prostate safely to a cytotoxic temperature. Experience with
      25 patients in whom external beam radiation therapy for prostate cancer had
      failed indicates that the treatment is safe. Although our series indicates that
      this therapy may be effective, further studies and longer followup are required
      in larger patient groups to confirm the potential role of this therapy as an
      option for recurrent and primary prostate cancer.

PMID- 11586208
TI  - Radioisotope guided pelvic lymph node dissection for prostate cancer.
AB  - PURPOSE: The localization of lymph node metastases in prostate cancer varies
      enormously. Due to high morbidity complete pelvic lymphadenectomy is often
      decreased to modified staging lymphadenectomy, resulting in loss of sensitivity
      for detecting micrometastases. Based on the promising results of intraoperative
      gamma probe application for identifying sentinel lymph nodes in malignant
      melanoma, breast and penis cancer, we identified sentinel lymph nodes in prostate
      cancer using a comparable technique. MATERIALS AND METHODS: In 117 patients
      99mtechnetium nanocolloid was transrectally injected directly into the prostate
      under ultrasound guidance 1 day before pelvic lymphadenectomy. Thereafter dynamic
      lymphoscintigraphy was done. Initially lymph nodes identified as sentinel lymph
      nodes by the gamma probe were removed and subsequently modified pelvic
      lymphadenectomy was performed. RESULTS: Lymphatic metastasis was detected in 28
      cases. An average of 4 sentinel lymph nodes were identified per patient in 25 of
      27 patients with micrometastasis, of which those in 24 contained micrometastasis
      for 96% sensitivity. In contrast, sensitivity of modified pelvic lymphadenectomy
      was 81.5%. In 16 patients only sentinel lymph nodes were positive. An average of
      21.8 lymph nodes (range 10 to 51) was dissected per patient at pelvic
      lymphadenectomy. Lymph node metastasis was noted in 6 of the 46 patients with a
      prostate specific antigen between 4 and 10 ng./ml. and in 8 of the 64 with a
      stage pT2 tumor. CONCLUSIONS: Our study shows individual variability of lymphatic
      drainage of the prostate and limited sensitivity for detecting positive lymph
      nodes when the pelvic dissection area is limited. Furthermore, our experience
      implies that the identification of sentinel lymph nodes is feasible, not only in
      breast cancer and malignant melanoma, but also in prostate cancer using a
      comparable technique.

PMID- 11586209
TI  - Momentary increase in plasma calcitonin gene-related peptide is involved in hot
      flashes in men treated with castration for carcinoma of the prostate.
AB  - PURPOSE: In women the vasodilatory neuropeptides calcitonin gene-related peptide
      and neuropeptide Y seem to be involved in menopausal hot flashes. We assessed
      whether plasma calcitonin gene-related peptide and neuropeptide Y change during
      hot flashes in men after castration. MATERIALS AND METHODS: We evaluated 10 men
      61 to 81 years old who underwent castration due to cancer of the prostate and had
      frequent hot flashes for changes in plasma calcitonin gene-related peptide and
      neuropeptide Y during 1 day at the outpatient clinic. At least 5 blood samples
      were obtained between flashes and 4 were obtained during each flash. The samples
      were analyzed for calcitonin gene-related peptide and neuropeptide Y using
      radioimmunoassay technique. Hot flashes were objectively recorded by measuring
      peripheral skin temperature and skin conductance. RESULTS: Plasma calcitonin gene
      related peptide increased 46% (95% confidence interval 21 to 71) during flashes
      in the 6 men in whom it was measurable. This change was statistically significant
      (p = 0.028). The concentration of neuropeptide Y was below the detection limit.
      Skin conductance and temperature increased significantly during flashes.
      CONCLUSIONS: Calcitonin gene-related peptide is involved in the mechanisms of hot
      flashes in men who underwent castration due to prostate carcinoma. Thus, there
      may be a similar mechanism of hot flashes in women and in men deprived of sex
      steroids.

PMID- 11586210
TI  - Skeletal fracture associated with androgen suppression induced osteoporosis: the
      clinical incidence and risk factors for patients with prostate cancer.
AB  - PURPOSE: Limited information exists regarding the long-term risk of skeletal
      fracture in men on androgen suppression for prostate cancer. In addition, the
      clinical risk factors predisposing them to skeletal fracture are incompletely
      defined. We define the long-term risk and clinical risk factors for skeletal
      fracture in patients with prostate cancer on chronic androgen suppression.
      MATERIALS AND METHODS: A total of 181 consecutive patients with prostate cancer
      on androgen suppression therapy were evaluated. The primary end point was
      skeletal fracture. Comprehensive demographic information was gathered, and
      univariate and multivariate analyses were performed to identify associations with
      skeletal fracture. RESULTS: The proportion of patients who had survived fracture
      free at 5 and 10 years on androgen suppression therapy was 96% and 80%,
      respectively. The black race (p = 0.009) and increased body mass index (p =
      0.024) were identified as protective against androgen suppression associated
      skeletal fractures. A significant correlation was identified between the duration
      of androgen suppression and risk of skeletal fracture (p = 0.003). CONCLUSIONS:
      Patients with prostate cancer treated with androgen suppression are at risk for
      skeletal fracture, and risk increases with the duration of therapy. Slender white
      men are at greatest risk. Conversely, black men and those with body mass indexes
      greater than normal (greater than 25 kg/m(2)) are at minimal risk despite a
      prolonged duration (10 years) of androgen suppression.

PMID- 11586211
TI  - Intraoperative and postoperative complications of radical retropubic
      prostatectomy in a consecutive series of 1,000 cases.
AB  - PURPOSE: We critically examined the intraoperative and postoperative
      complications associated with radical retropubic prostatectomy in the modern era.
      MATERIALS AND METHODS: Between April 18, 1994 and July 13, 2000, 1,000 men
      underwent radical retropubic prostatectomy performed by a single surgeon. The
      whole inpatient hospital medical record of 909 patients, the outpatient charts of
      955 and a self-administered patient survey completed by 679 were reviewed by 2
      data managers not involved in surgical management or followup care. In all 1,000
      cases at least 1 of the 3 data sources was reviewed. RESULTS: Mean patient age
      was 60.3 years. In 73%, 99.8% and 95.7% of cases serum prostate specific antigen
      was 10 ng./ml. or less, disease was clinical stage T1 or T2 and Gleason score was
      7 or less, respectively, while 19.9% of pathological specimens showed positive
      margins. There were 8 intraoperative complications (0.8%). All 5 rectal injuries
      and the single ureteral injury were detected during the initial surgical
      procedure and repaired without sequelae. Only 14 men (1.4%) had any other
      complications during hospitalization. Until postoperative day 30, 4 pulmonary
      emboli (0.4%) with or without deep vein thrombosis and 5 myocardial infarctions
      (0.5%) developed. There were no intraoperative or in-hospital postoperative
      deaths and only 1 postoperative death secondary to myocardial infarction during
      the initial 30 days. Reexploration was done for hemorrhage and a disrupted
      anastomosis in 3 and 2 cases, respectively. Mean hospitalization was 2.3 days,
      9.7% of patients required allogenic blood transfusion and 15 (1.5%) were
      rehospitalized. CONCLUSIONS: Our series represents a rigorous assessment of the
      complications associated with radical retropubic prostatectomy. It shows that in
      the hands of an experienced urological surgeon, this procedure is associated with
      minimal intraoperative and postoperative morbidity. Of the patients 98% had no
      intraoperative or postoperative complications. Our series enables appropriate
      contemporary comparisons to be made with laparoscopic prostatectomy and radiation
      therapy. This outcomes analysis implies that radical retropubic prostatectomy
      cannot be assumed to have greater morbidity than radiation therapy and it sets a
      high standard for those advocating laparoscopic radical prostatectomy.

PMID- 11586212
TI  - The cysteinyl leukotriene D4 receptor antagonist montelukast for the treatment of
      interstitial cystitis.
AB  - PURPOSE: The presence of leukotriene D4 receptors in human detrusor myocytes and
      increased urinary leukotriene E4 in patients with interstitial cystitis and
      detrusor mastocytosis imply a role for cysteinyl containing leukotrienes as
      proinflammatory mediators in this disease. We examined the efficacy of the
      cysteinyl leukotriene 1 receptor antagonist montelukast for treating patients
      with interstitial cystitis and detrusor mastocytosis. MATERIALS AND METHODS: Ten
      women in whom interstitial cystitis was diagnosed according to National Institute
      of Diabetes and Digestive and Kidney Diseases criteria and who also had detrusor
      mastocytosis with a minimum of 28 mast cells per mm.2 muscle tissue were included
      in this study. Patients received a single dose of montelukast daily for 3 months.
      The efficacy of treatment was determined by 24-hour urinary frequency, nocturia
      and pain using visual analog scales. RESULTS: After 1 month of montelukast
      treatment there was a statistically significant decrease in 24-hour urinary
      frequency, nocturia and pain which persisted during the 3 months of treatment.
      After 3 months 24-hour urinary frequency had decreased from 17.4 to 12 voidings
      (p = 0.009), nocturia had decreased from 4.5 to 2.8 (p = 0.019) and pain had
      decreased from 46.8 to 19.6 mm. on a visual analog scale (p = 0.006). No side
      effects were observed during treatment. CONCLUSIONS: Montelukast treatment
      resulted in significant improvement in urinary frequency and pain. Its efficacy
      for decreasing urinary frequency and pain imply a role of leukotriene receptor
      antagonists for managing interstitial cystitis but further placebo controlled
      clinical studies are needed.

PMID- 11586213
TI  - Correlation of beta-endorphin and prostaglandin E2 levels in prostatic fluid of
      patients with chronic prostatitis with diagnosis and treatment response.
AB  - PURPOSE: The chronic pelvic pain syndrome is a clinically defined symptom complex
      of unclear etiology. We have noted increased oxidative stress in the prostatic
      fluid of these patients, implying an active inflammatory response. Immune cells
      can produce the natural opioid beta-endorphin at the site of injury, which may
      modulate pain. We measured beta-endorphin and the inflammatory marker
      prostaglandin E2 in the expressed prostatic secretions of men with prostatitis,
      and correlated the results with symptoms. MATERIALS AND METHODS: Expressed
      prostatic secretions samples from 70 patients and 8 asymptomatic controls were
      collected and frozen. beta-Endorphin and prostaglandin E2 were measured by enzyme
      linked immunosorbent assay. Results were stratified according to prostatitis
      category and compared in individuals before and after therapy. RESULTS: In
      symptomatic patients beta-endorphin and prostaglandin E2 were not significantly
      different in categories II, IIIa and IIIb expressed prostatic secretions but they
      were higher than in controls. The mean beta-endorphin level plus or minus
      standard error of mean in symptomatic patients was significantly higher (23.8 +/-
      11 ng./ml. versus 8.7 +/- 4.7, p = 0.0001) and mean prostaglandin E2 was lower
      (6.01 +/- 2.9 ng./ml. versus 3.01 +/- 2.9, p = 0.001) after successful therapy
      with antibiotics or antioxidant phytotherapy, Prosta-Q (Farr Laboratories, Santa
      Clarita, California). CONCLUSIONS: We observed a correlation of higher
      prostaglandin E2 and lower beta-endorphin in symptomatic men with chronic
      prostatitis. Increased oxidative stress and inflammation may induce prostaglandin
      E2 production that would inhibit beta-endorphin release. Treatment with
      therapeutic agents that decrease oxidative stress, such as antibiotics and
      antioxidant phytotherapy, may function at least partially by increasing beta
      endorphin and decreasing prostaglandin E2.

PMID- 11586214
TI  - Sacral nerve stimulation in patients with chronic intractable pelvic pain.
AB  - PURPOSE: Transforamenal sacral nerve stimulation with an implantable
      neuroprosthetic device has been shown to benefit patients with chronic voiding
      dysfunction. In this study we measured the effectiveness of sacral nerve
      stimulation in 10 patients with chronic intractable pelvic pain. MATERIALS AND
      METHODS: After successful percutaneous trial stimulation, a neuroprosthetic
      sacral nerve stimulation device was surgically implanted in 10 patients with
      chronic intractable pelvic pain. Leads were placed in the S3 and S4 foramen in 8
      and 2 cases, respectively. Patients were evaluated throughout the study using a
      patient pain assessment questionnaire on a scale of 0-absent to 5-excruciating
      pain. Pain was assessed at baseline, during test stimulation, and 1, 3 and 6
      months after surgical lead implantation. An additional long-term assessment was
      done at a median followup of 19 months. RESULTS: Of the 10 patients with the
      implant 9 had a decrease in the severity of the worst pain compared to baseline
      at a median followup of 19 months. The number of hours of pain decreased from
      13.1 to 6.9 at the same followup interval. There was also an average decrease in
      the rate of pain from 9.7 at baseline to 4.4 on a scale of 10-always to 0-never
      having pain. At a median of 19 months 6 of 10 patients reported significant
      improvement in pelvic pain symptomology. CONCLUSIONS: These data imply that
      transforamenal sacral nerve stimulation can have beneficial effects on the
      severity and frequency of chronic intractable pelvic pain. Future clinical
      studies are necessary to determine the long-term effectiveness of this therapy.

PMID- 11586215
TI  - Predicting the success of retrograde stenting for managing ureteral obstruction.
AB  - PURPOSE: Retrograde ureteral stenting is often considered the first line option
      for relieving ureteral obstruction when temporary drainage is indicated. Several
      retrospective studies have implied that in cases of extrinsic obstruction
      retrograde ureteral stenting may fail and, therefore, percutaneous nephrostomy
      drainage is required. We examined the efficacy of retrograde ureteral stenting
      for resolving ureteral obstruction and identified clinical and radiological
      parameters predicting failure. MATERIALS AND METHODS: Enrolled in our prospective
      study were 92 consecutive patients with ureteral obstruction, which was bilateral
      in 8. Retrograde ureteral stenting was attempted in all cases by the urologist on
      call. When stent insertion failed, drainage was achieved by percutaneous
      nephrostomy. Patients were followed at 3-week intervals for 3 months. Each
      followup visit included a medical interview, blood evaluation, urine culture and
      ultrasound. Stent malfunction was defined as continuous flank pain manifesting as
      recurrent episodes of acute renal colic, 1 or more episodes of pyelonephritis,
      persistent hydronephrosis or elevated creatinine. Preoperative data and outcomes
      were compared in cases of intrinsic and extrinsic obstruction. Univariate and
      multivariate analysis was done to identify predictors of the failure of ureteral
      stent insertion and long-term function. RESULTS: The etiology of obstruction was
      intrinsic in 61% of patients and extrinsic in 39%. Extrinsic obstruction, which
      was associated with a greater degree of hydronephrosis, was located more distal.
      Retrograde ureteral stenting was successful in 94% and 73% of patients with
      intrinsic and extrinsic obstruction, respectively. At the 3-month followup stent
      function was maintained in all patients with intrinsic obstruction but in only
      56.4% with extrinsic obstruction. On multivariate logistic regression the type of
      obstruction, level of obstruction and degree of hydronephrosis were the only
      predictors of stent function at 3 months. Stent diameter and preoperative
      creatinine had no predictive value. CONCLUSIONS: Retrograde ureteral stenting is
      a good solution for most acutely obstructed ureters. In patients with extrinsic
      ureteral obstruction a more distal level of obstruction and higher degree of
      hydronephrosis are associated with a greater likelihood of stent failure. These
      patients may be better served by percutaneous drainage.

PMID- 11586216
TI  - Nickel-titanium shape memory alloy Memokath 051 ureteral stent for managing long
      term ureteral obstruction: 4-year experience.
AB  - PURPOSE: We present our 4-year experience with the thermo-expandable shape memory
      alloy Memokath 051 stent (Engineers and Doctors of Copenhagen, Copenhagen,
      Denmark) for managing long-term ureteral obstruction. MATERIALS AND METHODS: We
      used a nickel-titanium shape memory alloy ureteral stent to treat 28 patients 29
      to 86 years old (mean age 59.2). Ureteral obstruction was caused by malignancy in
      18 cases and by recurrent benign disease in 10. A total of 37 stents were
      inserted from November 1996 to November 2000 using general anesthesia. Mean
      followup was 19.3 months (range 3 to 35). RESULTS: Upper tract decompression was
      achieved in all cases. Currently 15 stents are functional in 13 patients, while 8
      patients died with a total of 13 functioning stents in place. In 7 patients 9
      stents were removed for various reasons. There has been no radiological evidence
      of encrustation to date. No patient has been rehospitalized with stent related
      sepsis pain or hematuria, resulting in improved quality of life. CONCLUSIONS:
      This stent seems to provide a significant benefit over conventional Double-J
      (Medical Engineering Corp., New York, New York) and other metallic stents. Its
      remarkable thermal memory permits removal, a feature that until recently was not
      available in any other metallic ureteral stent. Durable and complication-free
      decompression of the upper tract can be achieved with the Memokath 051.

PMID- 11586217
TI  - Artificial urinary sphincter for post-radical prostatectomy urinary incontinence:
      long-term subjective results.
AB  - PURPOSE: Incontinence affects between 3% and 60% of patients after radical
      prostatectomy. Insertion of an artificial urinary sphincter is a mainstay
      therapeutic option available to these patients. We assessed patient satisfaction,
      outcome and complications long after artificial urinary sphincter implantation.
      MATERIALS AND METHODS: From a data bank of 131 patients who underwent artificial
      urinary sphincter prosthesis insertion we identified 71 with a mean age of 72
      years who had also undergone radical prostatectomy and were available for
      evaluation. This group included 29 patients (40.8%) who received an earlier
      version of the AMS-800 (American Medical Systems, Minnetonka, Minnesota) and 42
      (59.2%) who received the newer narrow back cuff device. Information on surgical
      procedures and followup were obtained from a computerized database. Patients were
      also contacted by an impartial reviewer who administered a standard telephone
      questionnaire on the degree of continence, complications, other means used to
      help with urinary continence, proficiency in device operation and satisfaction.
      RESULTS: At a mean followup of 7.7 years (range 0.5 to 16) 19 patients (27%) used
      0, 23 (32%) used 1, 11 (15%) used 1 to 3 and 18 (25%) used more than 3 daily,
      while 1 used an external catheter. Surgical revision in 21 cases (29%) was
      required due to mechanical failure in 18 (25%), device erosion in 3 (4%) and
      infection in 1 (1.4%). The need for revision correlated significantly with the
      design of the sphincter (p = 0.005). Only 7 of the 42 patients in whom a narrow
      cuff AMS-800 was implanted needed revision versus 18 of the 23 with a previous
      design. Mean time to revision was 2.5 years (range 0.5 to 8). The device was
      removed in 2 cases (2.8%). Of the patients 41 (58%) are very satisfied, 14 (19%)
      are satisfied and 16 (23%) are unsatisfied with the device. The degree of
      satisfaction correlated with the number of pads used (p = 0.0005) and sphincter
      design (0.028) but not with the number of surgical revisions (p = 0.521) or
      patient age. CONCLUSIONS: The artificial urinary sphincter is a viable treatment
      option for post-radical prostatectomy incontinence with a high rate of continence
      and satisfaction for a long period after the procedure. Patients should be
      informed that complications necessitating device revision and explantation may
      appear late in followup. A standard definition of treatment success and studies
      of homogenous groups of patients with an artificial urinary sphincter would
      enable better understanding and patient education in the future.

PMID- 11586218
TI  - Results of high dose rate brachytherapy, anterior pelvic exenteration and
      external beam radiotherapy for carcinoma of the female urethra.
AB  - PURPOSE: We evaluated a multimodality approach to locally advanced urethral
      carcinoma in women. MATERIALS AND METHODS: Between August 1996 and July 1999, 6
      women were treated for locally advanced carcinoma of the urethra with anterior
      pelvic exenteration followed by high dose 192iridium intraoperative radiation
      therapy. Four of the 6 patients were also treated with neoadjuvant or concomitant
      platinum based chemotherapy. RESULTS: Two patients had no evidence of disease, 3
      had distant metastasis and 2 had local recurrence at a mean followup of 21 months
      (range 12 to 47). Radiation was relatively well tolerated with no major adverse
      events. CONCLUSIONS: High dose intraoperative brachytherapy followed by external
      beam radiation is relatively well tolerated. Local control seems to have
      improved. We must evaluate a larger cohort of patients to determine this impact
      of the combined modality on local control and patient survival.

PMID- 11586219
TI  - The relationship of penile rigidity and intracavernous vascular resistance in
      potent men during intracavernous pharmacological testing.
AB  - PURPOSE: We studied the relationship of penile rigidity and intracavernous
      vascular resistance in potent men during intracavernous pharmacological testing.
      MATERIALS AND METHODS: Enrolled in our study were 19 potent men undergoing
      intracavernous pharmacological testing for various reasons. Hemodynamic changes
      in response to the intracavernous injection of 20 microg. prostaglandin E1 were
      assessed by color Doppler sonography with simultaneous RigiScan (Dacomed Corp.,
      Minneapolis, Minnesota) monitoring of penile rigidity. The relationship of penile
      rigidity and intracavernous vascular resistance was determined by correlating
      hemodynamic data with recorded penile rigidity values. RESULTS: Maximal mean
      rigidity plus or minus standard deviation of the penile tip and base after
      intracavernous injection of prostaglandin E1 was 76.8% +/- 8.5% and 97.3% +/-
      4.7%, respectively. Penile tip and base rigidity correlated positively with the
      resistive index (r = 0.69 and 0.75, p <0.0001) and negatively with end diastolic
      velocity (r = -0.62 and -0.70, respectively, p <0.0001). The formula, rigidity = 
      128 + 195 x resistive index, was derived to describe the linear regression of
      penile base rigidity and the resistive index. The formula, rigidity = 59.8 - 3.3
      x end diastolic velocity, was derived to describe the linear regression of penile
      base rigidity and end diastolic velocity. CONCLUSIONS: Penile rigidity correlated
      strongly with intracavernous vascular resistance in potent men during
      intracavernous pharmacological testing. The resistive index and end diastolic
      velocity of the cavernous arteries may each be used to estimate penile rigidity
      quantitatively.

PMID- 11586220
TI  - Ultrastructure of the tunica albuginea in congenital penile curvature.
AB  - PURPOSE: We investigated the ultrastructure of the tunica albuginea in
      individuals with congenital penile curvature to explain the pathology of this
      disease. MATERIALS AND METHODS: Included in our study were 15 patients 17 to 24
      years old with congenital penile curvature. Study material consisted of samples
      of the tunica albuginea excised from the greater curvature of the corpus
      cavernosum during surgical correction. Control samples were obtained from the
      lesser curvature on the side opposite the study material during the same
      operation. The 2 types of tissue were analyzed using transmitter electron
      microscopy. RESULTS: Ultrastructural examination of the control material revealed
      numerous collagen fibers that were homogenous in size and organization on cross
      section. Periodic striation was typical in collagen that produced fibers. In the
      study group the tunica albuginea structure had a chaotic pattern of collagen
      fibers that formed bundles with disrupted 3-dimensional organization. Diameter of
      the fibers differed greatly on cross section. We observed periodic widening and
      fragmentation of collagen fibers with the complete disappearance of striation and
      transformation into electron dense, fibrous granulated material. Disrupted
      fibroblasts without cell membrane and cellular organelles between collagen fibers
      were also visible. There was elastin accumulation without any morphological
      differences in the control and study groups. CONCLUSIONS: Our results show that
      ultrastructural changes in the tunica albuginea may cause congenital penile
      curvature, possibly by altering mechanical properties.

PMID- 11586221
TI  - Effect of incision and saphenous vein grafting for Peyronie's disease on penile
      length and sexual satisfaction.
AB  - PURPOSE: We determined the effect of incision and saphenous vein grafting on
      penile length, erectile function and overall sexual satisfaction in men with
      Peyronie's disease. MATERIALS AND METHODS: A total of 24 consecutive men
      underwent plaque incision and saphenous vein grafting with postoperative daily
      use of a vacuum erection device. Erect penile length, pain, curvature and
      erectile function were assessed before and after surgery, and overall sexual
      satisfaction was scored from 1 to 5 by a validated instrument. RESULTS: Of the 22
      patients in whom adequate followup data were available mean penile length was
      increased 2.1 cm. as a result of surgery (p <0.001). Median score of overall
      satisfaction with sex life was 4 or moderately satisfied. Of the 86% of men who
      achieved sexual intercourse after surgery 54% used no erectile aids and 32%
      required sildenafil or intracavernous injection. Complete erectile dysfunction
      was present in 14% of cases. Patients who reported erectile difficulty
      preoperatively were significantly more likely to have erectile dysfunction
      postoperatively that required erectile aids. Arterial insufficiency on duplex
      Doppler ultrasound was associated with a higher likelihood of complete erectile
      dysfunction. Complications in 33% of patients included complete erectile
      dysfunction in 3 and significant persistent penile curvature in 1. CONCLUSIONS:
      Incision and venous grafting of plaque leads to statistically and clinically
      significant increases in penile length in men with Peyronie's disease.
      Preoperative erectile dysfunction and cavernous arterial insufficiency were
      associated with a higher risk of postoperative erectile dysfunction.
      Nevertheless, patients reported a high degree of satisfaction with their overall
      sex life.

PMID- 11586222
TI  - Improvement in emotional well-being and relationships of users of sildenafil.
AB  - PURPOSE: We estimated the association of sildenafil use with erectile function,
      relationship with sexual partner, functional status and emotional well-being in
      men with erectile dysfunction. MATERIALS AND METHODS: Letters were mailed to
      eligible patients at a university hospital urology and internal medicine clinic,
      and university affiliated community primary care clinics by the primary care
      provider or urologist inviting them to participate in the study. Of the eligible
      sample 124 men (53%) completed and returned a survey, including 85 who reported
      current sildenafil use. Change scores in these patients were calculated using the
      International Index of Erectile Function, marital interaction scale from the
      Cancer Rehabilitation Evaluation System Short Form, 5-item emotional well-being
      scale of the RAND 36-Item Health Survey and 12-Item Short Form Health Survey.
      RESULTS: Sildenafil users reported an 88% increase in erectile function scores,
      60% increase in overall sexual satisfaction and 36% increase in intercourse
      satisfaction related to the use of sildenafil (p <0.001). Of the respondents 38%
      indicated that using sildenafil had definitely improved quality of life. Likewise
      29% of respondents indicated that using sildenafil had definitely improved the
      relationship with their partner. With sildenafil there was a statistically
      significant improvement in the scores of erectile and sexual function (p <0.001),
      sexual partner relationship (p = 0.007) and emotional well-being (p <0.001). In a
      multivariate model improved erectile function and sexual partner relationship
      were each significantly associated with improved emotional well-being (R2 = 0.20,
      p <0.001). CONCLUSIONS: Sildenafil users reported significant improvements in
      erectile and sexual function that were associated with positive changes in
      emotional well-being and the sexual partner relationships with their sexual
      partner.

PMID- 11586224
TI  - Reconfiguration of the severely fibrotic penis with a penile implant.
AB  - PURPOSE: Using evidence based methods we prospectively evaluated the impact of a
      new surgical procedure on penile deformity caused by severe cavernous fibrosis.
      MATERIALS AND METHODS: In 10 patients with severe penile curvature, shortening
      and impaired penile rigidity due to fibrosis of the corpora cavernosa we made
      multiple relaxing incisions of the tunica albuginea and subsequently placed a 3
      piece inflatable penile implant. Patients were evaluated before and after the
      procedure by the International Index of Erectile Function and several general
      assessment questions. Preoperatively and postoperatively we measured flaccid and
      erect penile length. RESULTS: At the 6-month followup all International Index of
      Erectile Function domains were significantly improved compared with preoperative
      values. Average penile length was increased 2.3 and 3 cm. while flaccid and
      erect, respectively, compared with before surgery. Complete penile straightening
      was achieved in 9 of 10 cases (90%). Surgical reoperation was performed in 1
      patient (10%) in whom the implant was removed due to scrotal infection and in
      another (10%) in whom a further single relaxing incision of the fibrotic plaque
      was needed to attain complete penile straightening. CONCLUSIONS: Patients with
      severe penile curvature, shortening and impaired penile rigidity due to penile
      fibrosis may be offered this surgical alternative, which proved to be effective
      and safe in our preliminary series.

PMID- 11586223
TI  - Sildenafil versus the vacuum erection device: patient preference.
AB  - PURPOSE: We evaluated the preference of patients with erectile dysfunction who
      had been effectively treated with a vacuum erection device and then switched to
      sildenafil. MATERIALS AND METHODS: A total of 52 patients with erectile
      dysfunction who achieved satisfactory erectile function according to the
      International Index of Erectile Function (IIEF) while using a vacuum erection
      device were switched to an increasing dose of sildenafil (range 25 to 100 mg.)
      until satisfactory erection was maintained at least twice a week for at least 1
      month. The 2 treatment methods were not used concomitantly. A total of 36
      patients with a mean age of 59 years (range 35 to 77) who claimed to have
      achieved satisfactory erections with a vacuum erection device and sildenafil
      reported their preference to continue sildenafil or resume the use of a vacuum
      erection device, reasons for the choice and any adverse side effects. RESULTS: Of
      the 36 participants in whom the efficacy of sildenafil was similar to that of a
      vacuum erection device according to the IIEF scores (mean plus or minus standard
      deviation 61.6 +/- 10.4 and 62.5 +/- 6, respectively), 12 (33.3%) decided to
      resume use of a vacuum erection device (group 1) while 24 (66.6%) preferred to
      continue sildenafil (group 2). There were no statistically significant
      differences between the groups regarding patient age or the etiology and duration
      of erectile dysfunction. The increase in the IIEF score while using a vacuum
      erection device was higher in group 1 than 2, with a mean of 66.75 versus 60.4,
      respectively (p = 0.002). The adverse side effects of sildenafil were the main
      reasons for preferring a vacuum erection device. Fewer ejaculatory difficulties,
      efficacy, comfort and ease of use were the main reasons for choosing sildenafil.
      CONCLUSIONS: Even in an era of effective oral medication, the vacuum erection
      device remains a preferred treatment option for a substantial number of patients
      with erectile dysfunction.

PMID- 11586225
TI  - Need for sperm retrieval and cryopreservation at vasectomy reversal.
AB  - PURPOSE: Controversy exists on whether to obtain sperm for cryopreservation
      routinely at vasectomy reversal. With recent improvements in in vitro
      fertilization with intracytoplasmic sperm injection, it is now possible to obtain
      a small amount of testicular tissue for cryopreservation in the event of reversal
      failure. However, to our knowledge no studies exist of who is most likely to
      benefit from this procedure. MATERIALS AND METHODS: We reviewed 84 consecutive
      vasectomy reversals performed by 1 surgeon (J. I. S.) between July 1996 and March
      2000 with followup available for 77. We grouped cases by procedure as
      vasovasostomy, vasoepididymostomy and vasovasostomy with vasoepididymostomy as
      well as bilateral or unilateral. Sperm was retrieved at reversal in 15 of 46
      vasovasostomy (none used), 11 of 18 vasoepididymostomy (3 used) and 13 of 20
      vasovasostomy with vasoepididymostomy (none used) cases. RESULTS: The overall
      anastomotic patency rate after unilateral or bilateral vasovasostomy, unilateral
      vasovasostomy with contralateral vasoepididymostomy and unilateral or bilateral
      vasoepididymostomy was 96%, 83% and 57%, respectively. The natural pregnancy rate
      without in vitro fertilization was 57%, 50% and 14%, respectively. The most
      recent vasoepididymal anastomoses were performed by the Berger triangulation
      technique with a 78% patency and 25% pregnancy rate. Only 8% of men with banked
      sperm eventually used it for assisted reproductive techniques, in whom unilateral
      or bilateral vasoepididymostomy failed in all. CONCLUSIONS: We currently do not
      recommend routine sperm retrieval for cryopreservation in men who undergoing
      vasovasostomy. We encourage men who require bilateral vasoepididymostomy to bank
      sperm at reversal. In men who undergo vasovasostomy with vasoepididymostomy we
      base the decision on preoperative counseling and intraoperative findings.

PMID- 11586226
TI  - Quality of life of Iranian kidney "donors".
AB  - PURPOSE: The quality of life of Iranian kidney vendors was clarified. MATERIALS
      AND METHODS: A questionnaire was completed by 300 kidney vendors 6 to 132 months
      postoperatively (median 61). Interviews and living conditions were videotaped. In
      addition, the 300 vendors and 100 controls that underwent nephrectomy for benign
      disease completed the RAND 36-Item Health Survey (SF-36). RESULTS: Poverty
      prevented 79% of vendors from attending followup visits, and vending caused
      negative effects on employment in 65%. Of the families 68% strongly disagreed
      with vending, which caused rejection of 43% and increased marital conflicts in
      73% of vendors, including 21% who divorced. There were 70% of vendors isolated
      from society, and 71% had severe de novo postoperative depression and 60%
      anxiety. Vending caused somewhat (20%) to very (66%) negative financial effects.
      It also had negative effects on the physical abilities in 60% of vendors who were
      mainly unskilled laborers, and 80% were dissatisfied with postoperative physical
      stamina, which was decreased mostly by depression. Of the vendors 37% concealed
      the truth of kidney sale from anyone, 14% disclosed it only to spouses, 43% to
      first generation relatives and 94% were unwilling to be known as donors. The
      mental preoccupation with kidney loss was usually (30%) to always (57%) present
      and interfered negatively with vendor life, and 62% reported negative effects on
      sense of being useful. Effects on general health were somewhat (22%) to very
      (58%) negative. When thinking about vending, the majority cited negative
      feelings. They responded that if they had another chance 85% would definitely not
      vend again, and 76% strongly discouraged potential vendors from "repeating their
      error." Half the vendors were ready to lose greater than 10 years of life and 76%
      to 100% of properties to regain kidneys. Compared to controls, vendors had
      significantly lower scores on all SF-36 scales (p <0.001). CONCLUSIONS: Our
      sample is a good representative of Iranian kidney vendors, with the majority
      having psychosocial complications. Globally, the medical community should focus
      more attention on motivations, quality of life, health and opinions of kidney
      vendors.

PMID- 11586227
TI  - The Spanish National Institutes of Health-Chronic Prostatitis Symptom Index:
      translation and linguistic validation.
AB  - PURPOSE: The prominence of health related quality of life end points in
      international clinical research underscores the importance of well validated and
      translated measures to enable cross-cultural comparison. The National Institutes
      of Health (NIH)-Chronic Prostatitis Symptom Index (CPSI) assesses symptoms and
      health related quality of life in men with chronic nonbacterial, NIH type III
      prostatitis. To expand its use to Spanish speaking patients we performed a
      translation and linguistic validation. MATERIALS AND METHODS: The 9-item NIH-CPSI
      was translated into Spanish according to a standard methodology of 2 forward
      translations, 1 reconciled version, back translation of the reconciled version
      and 3 independent reviews by bilingual experts. The purpose of this methodology
      was to create a single universal Spanish version that would be acceptable to
      native Spanish speakers inside and outside of the United States. After the
      translation process the Spanish version was pre-tested in Argentina, Mexico,
      Spain and the United States. Patient responses were analyzed to identify
      necessary modifications. The internal consistency of the CPSI was evaluated using
      Cronbach's alpha. Pearson's product moment correlations were used to evaluate
      construct validity. RESULTS: Data were collected from chronic prostatitis
      patients, including 15 in Argentina, 15 in Mexico, 4 in the United States and 3
      in Spain. The translation had high reliability overall and in all subscales
      (Cronbach's coefficient alpha = 0.81 to 0.94), and the subscales correlated well
      with each other (r = 0.76 to 0.97). However, patients expressed difficulty in
      distinguishing the response categories "a menudo" ("often") from "normalmente"
      ("usually") in question 3. We revised "a menudo" to "muchas veces" ("much of the
      time") and "normalmente" to "casi siempre" ("almost always") to improve the
      distinctiveness of response categories. CONCLUSIONS: The Spanish NIH-CPSI has
      high reliability as well as face and construct validity in Spanish speaking men
      from various countries. The Spanish NIH-CPSI permits cross-cultural comparisons
      of men with chronic nonbacterial prostatitis.

PMID- 11586228
TI  - The impact of cancer treatment on quality of life outcomes for patients with
      localized prostate cancer.
AB  - PURPOSE: We evaluated the impact of localized prostate cancer treatment on
      general, cancer specific and symptom domains of quality of life for up to 5 years
      after diagnosis. MATERIALS AND METHODS: A total of 842 men from the Health
      Professionals Followup Study, diagnosed between 1993 and 1998, were included in
      cross-sectional analyses of quality of life associated with prostate cancer
      treatment. A subset of 146 men diagnosed after 1995 were followed prospectively.
      Quality of life was assessed with the Medical Outcomes Study Short-Form 36 Health
      Status Survey, Cancer Rehabilitation Evaluation System Short Form and University
      of California Los Angeles Prostate Cancer Index by mailed questionnaires. Primary
      treatment modality was taken from medical records and patient self-report.
      RESULTS: Significant treatment differences were observed in all quality of life
      measures, with the largest occurring in sexual, urinary and bowel symptoms. Bowel
      function was significantly worse in patients who received external radiation and
      brachytherapy compared with prostatectomy (p <0.05). Although they had better or
      equivalent urinary and sexual function (p <0.05), patients treated with external
      radiation, hormones or watchful waiting had lower generic quality of life scores
      in multiple domains compared with those who underwent prostatectomy. Patients who
      had brachytherapy had similar generic quality of life outcomes compared with
      prostatectomy in all domains. CONCLUSIONS: Our findings suggest that important
      differences in quality of life go beyond known physical symptoms associated with
      various prostate cancer treatment options, many of which involve making a trade
      off. It is important for patients with prostate cancer and health care providers
      to consider these differences while making treatment decisions.

PMID- 11586229
TI  - Laparoscopic cross-trigonal Cohen ureteroneocystostomy: novel technique.
AB  - PURPOSE: We describe a novel technique of laparoscopic transvesical cross
      trigonal Cohen anti-reflux ureteroneocystostomy. MATERIALS AND METHODS: A 10, an
      11 and a 32-year-old patient with symptomatic unilateral vesicoureteral reflux
      underwent laparoscopic cross-trigonal ureteral reimplantation. Two 5 mm. balloon
      tip ports were suprapubically inserted into the bladder. Using a transurethral
      resectoscope with a Collins knife a 4 to 5 cm. cross-trigonal submucosal trough
      was created from the refluxing ureteral orifice to the contralateral side of the
      bladder. The refluxing ureteral orifice and intramural ureter were completely
      mobilized intravesically, advanced transtrigonally and secured to the detrusor
      muscle at the apex of the trough with 3 deep interrupted sutures. The elevated
      mucosal flaps of the trough were suture approximated over the ureter to create a
      submucosal tunnel. All suturing was performed by freehand laparoscopic technique.
      RESULTS: Operative time was between 2.5 and 4.5 hours and blood loss was 10 to 50
      cc. Adequate submucosal trough creation, ureteral extravesical mobilization and
      intravesical advancement, and bladder mucosal flap reapproximation were done to
      create a submucosal tunnel in all cases. Satisfactory transtrigonal anchoring of
      the neoureteral orifice to the detrusor muscle and mucosa was achieved with 3
      stitches. Hospital stay was 2, 2 and 1 days in the 3 cases, and the Foley
      catheter remained in place for 3, 1 and 1 week, respectively. At 6 months reflux
      had resolved in 2 patients, while in 1 grade II reflux persisted, which was
      improved from grade IV preoperatively. All patients have remained infection-free
      without antibiotics. CONCLUSIONS: Laparoscopic transvesical cross-trigonal
      antireflux ureteral reimplantation is technically feasible. Intravesical
      laparoscopic suturing is possible. Potential advantages include a decreased
      hospital stay, decreased narcotic requirement and better cosmesis. Further
      experience is necessary to refine the technical nuances and evaluate outcomes
      compared to the open technique.

PMID- 11586230
TI  - An infrared ureteral stent to aid in laparoscopic retroperitoneal lymph node
      dissection.
AB  - PURPOSE: We used an infrared ureteral stent to aid in laparoscopic
      retroperitoneal lymph node dissection. MATERIALS AND METHODS: The patient was
      slender 31-year-old male. An infrared light emitting stent was used. RESULTS:
      With easy visualization of the ureter laparoscopic retroperineal lymph node
      dissection required 268 minutes. CONCLUSIONS: The infrared ureteral stent
      decreases the operative time of laparoscopic retroperitoneal lymph node
      dissection and makes it a safer and more acceptable treatment option.

PMID- 11586231
TI  - A technique for resection of small bladder tumors using a flexible cystoscope on
      an outpatient basis: bladder tumor resection with newly designed hot cup forceps.
AB  - PURPOSE: We describe a technique for resecting small papillary superficial
      bladder tumors using a new device and flexible cystoscope. MATERIALS AND METHODS:
      In a 79-year-old man 3 small recurrent papillary bladder tumors were resected
      transurethrally on an outpatient basis. The procedure was performed using a
      flexible cystoscope and a newly designed type of cup forceps with the patient
      under topical anesthesia. No urethral catheter remained indwelling after surgery
      and the patient was discharged home the same day. RESULTS: Bladder tumor
      resection using this technique was tolerable to the patient and postoperative
      bladder hemorrhage was not noted. Resected specimens were adequate for
      pathological tumor evaluation, which revealed grade 1 stage Ta superficial
      transitional cell carcinoma of the bladder. CONCLUSIONS: This easy technique
      seems to be tolerated well by the patient. Resected specimens should be adequate
      for evaluating the pathological grade and depth of stage Ta or T1 superficial
      bladder cancer. This technique may be an alternative to standard transurethral
      resection for removing small recurrent bladder lesions in select patients who
      prefer outpatient management of bladder tumors.

PMID- 11586232
TI  - Bilateral intrarenal adrenal glands in cadaveric donor kidneys resembling renal
      cell carcinoma on intraoperative frozen section.

PMID- 11586233
TI  - Bilateral adrenal Kaposi's sarcoma in an HIV seronegative patient.

PMID- 11586234
TI  - Pelvic hemangiopericytoma in a patient with mixed germ cell tumor of the testis.

PMID- 11586235
TI  - Synchronous bilateral chromophobe cell renal carcinoma.

PMID- 11586236
TI  - Radio frequency ablation of lung metastases from renal cell carcinoma.

PMID- 11586237
TI  - Long-term remission of transitional cell carcinoma after Bacillus Calmette-Guerin
      instillation in the renal pelvis.

PMID- 11586238
TI  - alpha-Fetoprotein producing renal pelvic and ureter tumor.

PMID- 11586239
TI  - Primary carcinoid tumor of the urethra.

PMID- 11586240
TI  - Malignant melanoma of the penis and sentinel lymph node biopsy.

PMID- 11586241
TI  - Epithelioid hemangioendothelioma of the testis.

PMID- 11586242
TI  - Successfully treated renal fungal ball with continuous irrigation of fluconazole.

PMID- 11586243
TI  - Re: von Hippel-Lindau disease: renal tumors less than 3 cm. can metastasize.

PMID- 11586244
TI  - Pressure flow measurement of hydronephrosis in children: a new approach to
      definition and quantification of obstruction.
AB  - PURPOSE: Hydronephrosis due to obstruction of the ureteropelvic junction is not
      uncommon in children. The critical level of outflow resistance characterizing
      obstruction remains to be established. It was previously found in our laboratory
      that the outflow resistance could be calculated in an animal model by
      servoregulating the infused flow to preset pressure levels. We determine whether
      this procedure is also feasible in patients with hydronephrosis. MATERIALS AND
      METHODS: A total of 46 patients with 48 hydronephrotic kidneys were examined.
      There were 32 boys and 14 girls with a diagnosis of hydronephrosis and suspected
      ureteropelvic junction obstruction who underwent a pressure flow study under
      general anesthesia for evaluation before possible surgery. The kidney was
      punctured percutaneously under ultrasonic guidance, and the study was performed
      under fluoroscopy. Flow levels were measured when steady state flow was achieved
      at pressures 5, 10, 15, 20, 25 and 30 mm. Hg greater than the intra-abdominal
      pressure. A conventional Whitaker test at an infusion rate of 10 ml. per minute
      was performed for comparison. The patient then underwent pyeloplasty if the
      kidney was considered obstructed. RESULTS: There were 2 patients excluded from
      evaluation because of significant leakage of contrast medium. Stable and
      repeatable recordings were obtained in all pressure flow studies but only in 7 of
      46 Whitaker tests. A total of 41 kidneys were considered obstructed at pressure
      flow studies and operated on. The resistance was pressure dependent. Thus, mean
      resistance in the previous range 5 to 15 mm. Hg was considered a good overall
      measure of outflow resistance. Mean resistance less than 0.75 was normal and
      greater than 1.25 obstruction. There were 7 patients who had crossing vessels and
      a high mean resistance (3 or greater). CONCLUSIONS: The Whitaker test proved to
      be of no value for calculating the outflow resistance in ureteropelvic junction
      obstruction. The pressure flow study is superior to the Whitaker test for
      determining the outflow resistance and also allowing categorization of
      ureteropelvic junction obstruction.

PMID- 11586245
TI  - Angiotensin type II receptor expression and ureteral budding.
AB  - PURPOSE: Deletion of the angiotensin type II receptor gene (Agtr2) in mice
      results in a spectrum of urinary tract anomalies similar to that in humans. The
      mechanism behind this anomalous development is poorly understood. We evaluated
      Agtr2 expression as it relates to normal and abnormal ureteral budding. MATERIALS
      AND METHODS: A total of 400 wild type mice were inspected at birth for gross
      evidence of a urinary tract anomaly. In addition, the urinary tracts of 30 wild
      type embryos were evaluated at 11.0/11.5 and 13.5 weeks of gestation. These
      embryos were examined for ureteral budding site via section and whole mount in
      situ hybridization with c-ret probe and Agtr2 expression via in situ
      hybridization with Agtr2 riboprobe. There were 740 newborn mice homozygous for
      the null mutation of Agtr2 also evaluated along with 55 angiotensin type II
      knockout embryos at the aforementioned gestational ages. RESULTS: All wild type
      newborn animals were grossly normal. Of the angiotensin type II knockout newborns
      23 (3.1%) had gross abnormalities of the urinary tract at birth. The predominant
      finding was a duplicated collecting system associated with a hydronephrotic upper
      pole moiety. These duplicated collecting systems fulfilled the Meyer-Weigert law.
      Interestingly, 25 (59.5%) of the knockout embryos showed abnormal ureteral
      budding. However, in wild type embryos Agtr2 was expressed at this "ectopic"
      cranial site between the wolffian duct and metanephric mesenchyme. CONCLUSIONS:
      Although not the sole regulator, angiotensin type II receptor expression may have
      a role in the embryological development of the urinary tract by inhibiting
      aberrant ureteral budding. A defect in this inhibitory process appears to cause
      ectopic ureteral budding, and may subsequently lead to renal dysplasia and other
      congenital anomalies of the kidney and urinary tract.

PMID- 11586246
TI  - High resolution ultrasound characterization of early allograft hemodynamics in
      pediatric living related renal transplantation.
AB  - PURPOSE: Allograft vascular thrombosis occurs in 5% to 10% of pediatric renal
      transplants. The hemodynamics of renal allograft immediately after implantation
      is unclear. High resolution Doppler ultrasound of the renal allograft performed
      in the operating room after incision closure is an effective and objective method
      to advance our understanding of baseline renal allograft hemodynamics, and
      identify unsuspected vascular complications early enough to ensure prompt
      surgical repair. MATERIALS AND METHODS: Between September 1998 and July 2000 high
      resolution, color power Doppler ultrasound was prospectively performed on 21
      living related renal transplants in the operating room immediately after incision
      closure. Each ultrasound described allograft anastomotic blood flow, direction of
      diastolic flow, parenchymal perfusion and resistive indexes. RESULTS: There were
      20 (95%) allografts with good power Doppler perfusion that had satisfactory
      immediate function with no vascular complications at 9 to 26-month followup.
      Initially, anastomotic turbulence was described in 15 (71%) allografts, and
      resistive indexes were abnormal in 8 (38%). Turbulence and abnormal resistive
      index normalized in all allografts by 1-month followup. Ultrasound of 1 allograft
      identified unsuspected poor perfusion and reversal of diastolic flow in the
      operating room after incision closure. In another allograft in which a 4-hour
      post-transplant ultrasound was compared with the baseline study in the operating
      room an unsuspected thrombosis of the right common iliac vein was confirmed.
      CONCLUSIONS: Good parenchymal perfusion and forward diastolic flow after renal
      reperfusion correlated well with immediate graft function. Initial turbulence and
      abnormal resistive index in the presence of favorable perfusion are misleading
      and not independent predictors of graft function. Ultrasound performed in the
      operating room identified 2 unsuspected major vascular complications facilitating
      prompt surgical correction.

PMID- 11586247
TI  - Heterotopic bone formation in the urinary tract.

PMID- 11586248
TI  - Development of small calculi in an infant with bilateral single system
      ureteroceles.

PMID- 11586249
TI  - Is the pediatric ureter as efficient as the adult ureter in transporting
      fragments following extracorporeal shock wave lithotripsy for renal calculi
      larger than 10 mm.?
AB  - PURPOSE: We determined whether the thin ureter of the young child transports
      stone fragments after extracorporeal shockwave lithotripsy (ESWL) as efficiently
      as the adult ureter does. This determination was done by comparing the outcome
      after lithotripsy of renal stones greater than 10 mm. between young children and
      adults. MATERIALS AND METHODS: Our study group consisted of 38 children 6 months
      to 6 years old (median 3 years) with renal stones greater than 10 mm. in
      diameter. This group was further divided into 3 subgroups according to the
      longest stone diameter on plain abdominal film. There were 21 children with a
      renal stone diameter of 10 to 15 mm. (subgroup 1), 8, 16 to 20 mm. (subgroup 2)
      and 9 greater than 20 mm. (subgroup 3). The control group consisted of 38 adults
      older than 20 years randomly selected from the local ESWL registry. Each adult
      was matched with a child regarding stone diameter and localization. The control
      group was similarly divided into subgroups 1a, 2a and 3a. ESWL was performed with
      the unmodified Dornier HM-3 lithotriptor (Dornier Medical Systems, Inc.,
      Marietta, Georgia). The stone-free rate, complication rate, and need for tubes,
      including stent or nephrostomy, and greater than 1 ESWL session were compared.
      RESULTS: The stone-free rate was 95% in the study and 78.9% in the control group
      (p = 0.086). Stone-free rates were 95%, 100% and 89% in subgroups 1, 2 and 3, and
      95%, 65% and 56% in subgroups 1a, 2a and 3a, respectively. There were 10 children
      and 4 adults who underwent greater than 1 ESWL session (p = 0.14). Then there
      were 10 children and 6 adults who required a tube before ESWL (p = 0.04), and
      almost all of them were included in subgroups 3 and 3a. Early complications were
      rare in both the study and control groups. Late complications had included 2
      cases of Steinstrasse in the control and none in the study group. CONCLUSIONS:
      The stone-free rate after ESWL for large renal stones is higher in young children
      compared to adults with matching stone size. Renal stones greater than 20 mm.
      often require more than 1 ESWL session. The pediatric ureter is at least as
      efficient as the adult for transporting stone fragments after ESWL.

PMID- 11586251
TI  - Ureteral substitution with a stapled neoureter: a simplified Boari flap.
AB  - PURPOSE: We evaluate a new technique that will quickly and easily replace a long
      segment of ureter by creating a tapered neoureter (Boari flap) with bladder wall
      and absorbable staples. MATERIALS AND METHODS: A neoureter was created in 14 pigs
      with native bladder and 75 mm. Polysorb gastrointestinal anastomosis staplers (U.
      S. Surgical, Norwalk, Connecticut). Urine culture and serum creatinine were
      obtained before neoureter creation. Neoureter length and time to construct were
      recorded. At 6 weeks serum creatinine was repeated, and ureteral stent removed
      with evaluation of the staple lines for stones and residual staples. At 4 months
      intravenous pyelogram, cystogram and serum creatinine were obtained before
      necropsy. The bladder, neoureter and kidneys were examined grossly and
      histologically for hydronephrosis, staples, stones and stenosis. RESULTS: Mean
      neoureter length was 13.4 cm. and mean time to construct was 15 minutes.
      Laboratory results were unremarkable. Of the 14 pigs 2 died of pneumonia before
      stent removal, and at autopsy neither had evidence of hydronephrosis nor
      anastomotic stricture. In the remaining 12 pigs there was no evidence of residual
      staples or stone formation with mucosa covering the staple line at cystoscopy and
      necropsy. Successful neoureter substitution was performed in 9 pigs with no gross
      or histological changes. There were 3 pigs that had evidence of hydronephrosis
      with histological findings of chronic pyelonephritis and 2 of them appeared
      atrophic compared to the contralateral kidney. CONCLUSIONS: Our study
      demonstrates a new technique for ureteral substitution with bladder and
      absorbable staples that may be performed quickly and easily. Furthermore, we show
      that absorbable staples can be safely incorporated into the urinary tract with
      minimal worry about encrustation or calculus formation.

PMID- 11586250
TI  - Penoscrotal transposition: review of 53 patients.
AB  - PURPOSE: Penoscrotal transposition is a rare congenital abnormality of the
      external genitalia. We determine whether there is a genetic basis for this
      disorder, define the incidence of coexisting organ system anomalies, and compare
      the results of surgical techniques to correct transposition and hypospadias.
      MATERIALS AND METHODS: We report the largest, single institution series of 53
      patients 1 day to 30 years old with penoscrotal transposition. RESULTS: Of the
      patients 13% had a family history of penoscrotal transposition. Interestingly, we
      identified 1 family in which inheritance occurred in an X-linked recessive
      manner. There were 17 (32%) patients who had abnormalities in other organ
      systems, with the genitourinary system in 9 affected most. A total of 79% of
      patients had hypospadias and 81% chordee. These anomalies were corrected with a
      single stage Thiersch-Duplay urethroplasty in 6 patients and complex repair with
      bladder or buccal mucosa, or a staged procedure in 34. Complication rates for
      urethroplasty were similar. Correction of the transposition included a Glenn
      Anderson technique in 37 patients, Singapore rotational flaps in 7 and V-Y
      procedure in 6. The Glenn-Anderson repair produced the best cosmetic results and
      was associated with a significantly lower incidence of complications (p = 0.001).
      CONCLUSIONS: We identified a subgroup of patients with a family history of
      penoscrotal transposition. Treatment requires an awareness of the association
      with other organ system anomalies. The Glenn-Anderson technique was the most
      successful method to correct transposition. Most patients required release of
      chordee and complex urethroplasty for hypospadias.

PMID- 11586252
TI  - Safety of ketorolac in the pediatric population after ureteroneocystostomy.
AB  - PURPOSE: Ketorolac has been used to provide effective postoperative analgesia in
      children and decreases hospitalization for pediatric patients undergoing
      ureteroneocystostomy. However, it can cause severe side effects, including
      increased bleeding and renal insufficiency, which can be devastating in a child.
      Little has been reported on the safety of ketorolac by evaluating creatinine,
      hematocrit and complications. MATERIALS AND METHODS: An institutional
      retrospective review was performed during an 18-month period in which 118
      patients underwent ureteroneocystostomy. One group containing 50 patients
      received caudal anesthetic preoperatively and narcotic analgesics
      postoperatively, while another 68 received caudal anesthetic preoperatively and
      ketorolac postoperatively. Patient ages, type of procedure, preoperative and
      postoperative creatinine and hematocrit, and complications were noted in each
      cohort. RESULTS: Average patient age of the control analgesic and ketorolac
      groups was 5.3 years (range 1 to 17) and 5.5 (1 to 12), respectively. There was
      no statistical difference between postoperative creatinine (0.68 and 0.65
      mg./dl.) and hematocrit (33% and 34%) between the groups. One patient in each
      group had increased creatinine postoperatively. Minor complications, for example
      ileus and bladder spasms, were equivalent in both groups. No patient receiving
      ketorolac had any allergic or hypersensitivity reaction to the medication, and no
      major complications were reported. CONCLUSIONS: Ketorolac given after
      ureteroneocystostomy did not cause a significant decrease in hematocrit, increase
      in creatinine or overall complications. Because of the safety of ketorolac in our
      series, and ability to decrease hospital stay and narcotic requirements in
      children as reported previously, it is used as standard postoperative protocol
      after ureteroneocystostomy at our institution.

PMID- 11586253
TI  - Congenital prepubic sinus: a variant of dorsal urethral duplication suggested by
      immunohistochemical analysis.
AB  - PURPOSE: Congenital prepubic sinus is a rare disorder of uncertain etiology.
      Immunohistochemical staining is used to elucidate the etiology of the sinus.
      MATERIALS AND METHODS: We treated 5 patients with congenital prepubic sinus. A
      sinogram delineated the tract, which was then excised. In addition to routine
      hematoxylin and eosin stain of the 5 specimens, immunohistochemical analysis was
      also performed with smooth muscle and sarcomeric actin, high (34betaE12) and low
      molecular weight cytokeratin (35betaH11), and cytokeratin 7 antibodies. RESULTS:
      The 2 females and 3 males were 1 month to 14 years old. All patients had
      presented with purulent discharge from the sinus opening. Hematoxylin and eosin
      stain demonstrated transitional and squamous epithelium lining the sinus.
      Immunohistochemical study showed that the stain with 3 cytokeratin antibodies was
      moderately to strongly positive in all patients at the proximal end, low
      molecular weight cytokeratin weakly to moderately positive and cytokeratin 7
      weakly positive to negative in 4 at the distal end. The results suggested that
      the lining epithelium was transitional proximally and squamous distally. An
      exception was a female patient who had the shortest tract lined with squamous
      epithelium only. Furthermore, smooth muscle but not sarcomeric actin demonstrated
      smooth muscle bundles around the sinus tract in 4 patients. CONCLUSIONS: The
      existence of transitional epithelium in the proximal part of the sinus and
      presence of smooth muscle bundles around it reinforce the theory that congenital
      prepubic sinus is a variant form of dorsal urethral duplication.

PMID- 11586254
TI  - Efficacy of endoscopic subureteral polydimethylsiloxane injection for treatment
      of vesicoureteral reflux in children: a North American clinical report.
AB  - PURPOSE: Subureteral injection of bulking agents is an accepted surgical
      treatment of vesicoureteral reflux in children. Polydimethylsiloxane, a silicone
      elastomer, is an ideal agent because of bulky consistency, lack of migration,
      minimal local inflammatory reaction and is safe in laboratory animals. We record
      our experience with endoscopic subureteral polydimethylsiloxane injection in
      children for vesicoureteral reflux. MATERIALS AND METHODS: During a 2-year period
      16 boys and 58 girls, with an average age of 8 years, with 112 refluxing ureters
      underwent endoscopic subureteral polydimethylsiloxane injection to treat
      vesicoureteral reflux. Vesicoureteral reflux was grade I in 8, II in 43, III in
      50, IV in 10 and V in 1 ureter. Operative indications were breakthrough urinary
      tract infection in 29 children, nonresolution of reflux 38 and high grade reflux
      7. All procedures were on an outpatient basis and performed with patient under
      general anesthesia. All children had a postoperative ultrasound and voiding
      cystourethrogram at 12 weeks. Followup was from 6 to 24 months. RESULTS: Overall,
      reflux was corrected in 90 (81%) ureters and 56 (76%) children after a single
      injection. With repeat injection reflux was corrected in 101 (90%) ureters and 63
      (85%) children. Correction by grade was 85%, 84%, 80%, 45% and 0% for grades I to
      V, respectively. With repeat injection correction was 100%, 92%, 90% and 55% for
      grades I to IV, respectively. There were no surgical complications. De novo
      contralateral reflux developed in 2 (3%) children. There were 3 (4%) children who
      required open ureteral reimplantation for failed injection. Detection of the
      polydimethylsiloxane implant by followup ultrasound was 89% sensitive and 86%
      specific for the correction of reflux. CONCLUSIONS: Endoscopic subureteral
      polydimethylsiloxane injection is an effective treatment of vesicoureteral reflux
      in children. The procedure is safe with low associated morbidity. The presence of
      the polydimethylsiloxane implant can be documented accurately by ultrasound, and
      there is a strong correlation between implant stability and correction of reflux.

PMID- 11586255
TI  - Long-term followup of children treated with dextranomer/hyaluronic acid copolymer
      for vesicoureteral reflux.
AB  - PURPOSE: Dextranomer/hyaluronic acid copolymer is a novel substance that has
      favorable properties for endoscopic treatment of vesicoureteral reflux. We assess
      the long-term efficacy and safety of this treatment of children. MATERIALS AND
      METHODS: Children 1 to 15 years old with grade III or greater vesicoureteral
      reflux were eligible for enrollment in our study. All patients received
      endoscopic treatment with dextranomer/hyaluronic acid copolymer and were
      scheduled to have a voiding cystourethrogram 3 and 12 months after implantation.
      Children with reflux grade III or greater after treatment received up to 2 more
      implantations, and those with persistent reflux were referred for open surgery.
      In some cases long-term clinical followup was accompanied by a late voiding
      cystourethrogram. RESULTS: A total of 228 patients received endoscopic treatment.
      The efficacy population was comprised of 221 children, including 67 who received
      2 and 8 who received 3 implantations. Endoscopic treatment was performed without
      complications in all cases. Patients were followed clinically for 2 to 7.5 years
      (mean 5). On the last voiding cystourethrogram 68% of patients had a positive
      response (grade I or less) and 81% had no dilating reflux. The corresponding
      results for treated ureters were 75% and 85%, respectively. Only 27 (12%)
      patients were referred for open surgery. A late voiding cystourethrogram was
      performed in 49 patients 2 to 5 years after treatment. Of the ureters free of
      reflux (grade 0) 3 to 12 months after treatment 96% remained free of dilating
      reflux. Adverse events occurred in association with implantation in only 2% of
      patients, although urinary tract infection subsequently developed in 8%.
      CONCLUSIONS: Endoscopic treatment with dextranomer/hyaluronic acid copolymer was
      effective and well tolerated in children with vesicoureteral reflux. Long-term
      followup indicated that there was no deterioration in patients responding
      positively to treatment.

PMID- 11586256
TI  - Interactive computer games for treatment of pelvic floor dysfunction.
AB  - PURPOSE: We reviewed our experience with a conservative medical program and
      computer game assisted pelvic floor muscle retraining in patients with voiding
      dysfunction to substantiate our previous findings that demonstrated improvement
      and/or cure in a majority of patients, and identify factors that may be
      associated with unsuccessful treatment. MATERIALS AND METHODS: All patients
      presenting with symptoms of dysfunctional voiding enrolled in our pelvic floor
      muscle retraining were examined. Cases were subjectively evaluated for
      improvement of nocturnal enuresis, diurnal enuresis, constipation, encopresis and
      incidence of break through urinary tract infection. Patients in whom our initial
      conservative approach that included our biofeedback program failed were further
      treated with medication, and outcomes were reviewed as well. Fisher's exact test
      was used for statistical analysis to identify factors that may predict failure
      with our program. RESULTS: During the last 2 years 134 girls and 34 boys were
      enrolled in the pelvic floor muscle retraining program. Of the patients 160 (95%)
      were compliant with the program. Mean patient age was 7.6 years (range 4 to 18).
      The average number of hourly treatment sessions was 4.9 (range 2 to 13).
      Uroflowmetry and electromyography demonstrated a flattened flow pattern with
      increased post-void residual volume in 32% of patients, flattened flow pattern
      with normal post-void residual 47%, staccato flow pattern with increased post
      void residual 11% and staccato flow pattern with normal post-void residual 10%.
      Subjective improvement was demonstrated in 87% (146) of patients, while 13% (22)
      had no improvement. Statistically significant predictors of failure included
      bladder capacity less than 60% of predicted volume (p <0.03) and patient
      noncompliance (p <0.04). Twelve patients who had no improvement with biofeedback
      were treated with medication and 10 (83%) improved. Multichannel urodynamics or
      spinal magnetic resonance imaging (MRI) was obtained in only 7 (4%) of our
      patients with no neurological lesion identified by spinal MRI. CONCLUSIONS: A
      conservative program combined with computer game assisted pelvic floor muscle
      retraining improves symptoms in most patients with voiding dysfunction. A
      majority of patients can be treated without medication. However, in a select
      population of patients with a small capacity bladder in whom biofeedback fails,
      anticholinergic medication appears to alleviate symptoms. In our experience
      almost all patients presenting with symptoms of voiding dysfunction can be
      treated without multichannel urodynamics, spinal MRI or medication.

PMID- 11586257
TI  - Recognition of bladder instability on voiding cystourethrography in infants with
      urinary tract infection.
AB  - PURPOSE: We evaluate voiding cystourethrography as a method for identifying
      bladder instability in infants. MATERIALS AND METHODS: Cystometry was combined
      with voiding cystourethrography in 79 male and 64 female infants with first time
      urinary tract infection. Bladder wall irregularity, elongation of bladder shape,
      and filling of the posterior urethra were transient radiological signs occurring
      during bladder filling and were considered to reflect bladder instability. A
      pediatric radiologist looked for these signs on all 480 films exposed during
      bladder filling. The results were correlated to simultaneous detrusor pressure
      recordings. The analysis was repeated independently by a urologist to evaluate
      the reliability of the radiological signs used. RESULTS: The sensitivity and
      specificity were both 90% in the evaluation of radiological signs of bladder
      instability. Filling of the posterior urethra was the least frequently reported
      radiological sign, which was seen at 53% of unstable contractions. However, when
      this sign was reported, instability was usually correctly detected (85%).
      Evaluation accuracy had improved with increasing numbers of noted signs per film.
      This accuracy had included 29%, 67% and 91% of unstable contractions that were
      correctly diagnosed when 1, 2 or 3 signs were noted, respectively. The number of
      noted signs was positively related to the strength of the unstable detrusor
      contraction. Urologist evaluations had similar results to the radiologist,
      although the sensitivity was somewhat lower (79% and 90%, respectively).
      CONCLUSIONS: Unstable detrusor contractions could be identified in infants by
      evaluation of radiological signs on voiding cystourethrography. Findings of
      bladder wall irregularity, elongation of bladder shape and filling of the
      posterior urethra indicated unstable detrusor contraction. The more such findings
      are observed, the stronger the indication.

PMID- 11586258
TI  - Treatment of incontinence in children with bladder exstrophy after rectal urinary
      diversion: the anal sling procedure.
AB  - PURPOSE: An original technique for reinforcement of the anal sphincter using a
      sling prosthesis with a flexible fixing point that prevents incontinence and
      rectal prolapse is presented. MATERIALS AND METHODS: Of 43 patients with
      exstrophy who have undergone urinary rectal diversion between 1988 and 1997
      incontinence was observed in 9 boys and 5 girls. From January 1993 to December
      1998 these children were treated with an original method, the anal sling
      procedure. RESULTS: There were no postoperative complications. Investigations
      revealed no urinary or fecal incontinence after a mean followup of 3.2 years
      (range 6 months to 61/2 years). CONCLUSIONS: A short and simple operation
      eliminates incontinence after rectal urinary diversion in patients with bladder
      exstrophy. It can be used as an alternative to the formation of an isolated
      urinary reservoir.

PMID- 11586259
TI  - Renin containing cells are present predominantly in scarred areas but not in
      dysplastic regions in multicystic dysplastic kidney.
AB  - PURPOSE: Hypertension is an important complication of multicystic dysplastic
      kidney and it has been suggested that it is induced by renin. Little information
      is available on renin production in this disease. To assess renin production we
      examined the distribution of renin containing cells in multicystic dysplastic
      kidneys using immunohistochemical methods. MATERIALS AND METHODS:
      Immunohistochemical examination of renin was performed in 29 multicystic
      dysplastic kidneys from 14 boys and 15 girls 1 month to 10 years old using rabbit
      anti-human renin antibodies. In all cases normal renal function was confirmed by
      the serum creatinine level and no proteinuria on urinalysis. Two patients had the
      complication of hypertension before removal of the multicystic dysplastic kidney
      but plasma renin activity was normal. RESULTS: Immunostaining of renin was
      observed in 26 of 29 multicystic dysplastic kidneys (90%). Histologically
      multicystic dysplastic kidney involved scarred and dysplastic areas. Renin
      positive cells were observed predominantly in the scarred areas, mainly in the
      juxtaglomerular apparatus of mature glomeruli, interlobular arteries and some
      mature tubules. Immunopositive renin was sparsely noted in the juxtaglomerular
      apparatus or Bowman's capsules of occasional immature glomeruli in dysplastic
      areas. CONCLUSIONS: Our observations suggest that multicystic dysplastic kidney
      may have the ability to produce renin. Renin producing cells in the
      juxtaglomerular apparatus of mature glomeruli and interlobular arteries in the
      scarred areas may be the predominant source of renin production in this organ.

PMID- 11586260
TI  - A primate model of renal ischemia-reperfusion injury for preclinical evaluation
      of the antileukocyte function associated antigen 1 monoclonal antibody
      odulimonab.
AB  - PURPOSE: We established a primate model to investigate the effects of the
      antileukocyte function associated antigen 1 (CD 11a) mAb odulimomab (Imtix
      Sangstad, Lyon, France) for preventing renal ischemia-reperfusion injury.
      MATERIALS AND METHODS: We randomly divided 34 Macaca cynomolgus monkeys into
      groups 1 and 2, which received a renal autograft after 2 hours of cold ischemia,
      and groups 3 and 4, which received the autograft after 24 hours of cold ischemia.
      Before cold ischemia all harvested kidneys were subjected to 30 to 45 minutes of
      warm ischemia. Groups 1 and 3 monkeys were treated with an antileukocyte function
      associated antigen 1 mAb before cold ischemia and then for 3 days, while groups 2
      and 4 monkeys received an IgG1 isotype control. In all groups renal function was
      investigated before warm ischemia and 72 hours after reperfusion. Serum
      creatinine and the leukocyte count were determined daily. Histological studies
      were done and lactoferrin was measured in the autotransplanted kidney 72 hours
      after reperfusion. RESULTS: A decrease in renal function was shown after 2 hours
      of cold ischemia with tubular necrosis and mild cell infiltration, while after 24
      hours of cold ischemia there was severe renal failure with tubular and glomerular
      necrosis, and leukocyte infiltration. A significant improvement in renal function
      and decrease in kidney lactoferrin content was evident in group 1 compared to
      group 2 at 72 hours, while no significant difference was noted in groups 3 and 4.
      No difference in histological patterns was evident in treated and untreated
      animals. CONCLUSIONS: This study provides evidence for the validity of this
      ischemia-reperfusion injury model in primates. The protective effects of
      antileukocyte function associated antigen 1 mAb on renal injury was not as
      dramatic as in rodent models but a significant improvement in renal function was
      observed in treated animals after 2 hours of cold ischemia.

PMID- 11586261
TI  - Laparoscopic bladder flap ureteral reimplantation: survival porcine study.
AB  - PURPOSE: The bladder or Boari flap is a useful technique for ureteroneocystostomy
      when the distal ureter is too short to reach the bladder without undue tension.
      We report our experience with laparoscopic Boari flap ureteroneocystostomy in the
      chronic porcine model. MATERIALS AND METHODS: Six female farm pigs underwent
      unilateral laparoscopic Boari bladder flap ureteroneocystostomy. Refluxing direct
      ureteral reimplantation was performed in the initial 3 animals. In the next 3
      animals a submucosal tunnel was formed to achieve nonrefluxing
      ureteroneocystostomy into the Boari flap. The animals were sacrificed 6 weeks
      after surgery. At sacrifice ascending cystography, ipsilateral antegrade
      pyelography and autopsy examination of the ureteroneocystostomy site was
      performed. RESULTS: No intraoperative or postoperative complications were noted.
      Average operative time was 140 minutes. Postoperatively serum creatinine and
      hemoglobin were normal in all pigs. All 3 animals with direct
      ureteroneocystostomy into the Boari flap had free reflux into the kidney and all
      3 with a submucosal tunnel reimplant had no reflux on ascending cystography and
      free drainage on antegrade pyelography. Autopsy confirmed a patent anastomotic
      site in all 6 cases. CONCLUSIONS: Laparoscopic ureteroneocystostomy using the
      Boari bladder flap technique is feasible. Our survival porcine model confirms the
      successful application of the refluxing and nonrefluxing technique of ureteral
      reimplantation. Clinical application of the technique has the potential to
      decrease patient morbidity associated with traditional open surgery.

PMID- 11586262
TI  - Bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase
      expression in localized human prostatic adenocarcinoma as predictors of clinical
      outcome: a clinicopathological and immunohistochemical study of 43 cases.
AB  - PURPOSE: Skeletal metastases are the hallmark of advanced prostate cancer and
      recurrence after local surgery is common. Currently to our knowledge no
      biological markers predict the risk of disease progression in individuals with
      localized prostate cancer. In a search for predictive markers we evaluated the
      expression of bone sialoprotein and bone morphogenetic protein 6, 2 bone related
      proteins, and the angiogenic factor thymidine phosphorylase. MATERIALS AND
      METHODS: The study population included 43 men who presented with localized
      prostate cancer treated with radical prostatectomy. Bone sialoprotein, bone
      morphogenetic protein 6 and thymidine phosphorylase expression was assessed by
      immunohistochemical testing. Results were analyzed in relation to pathological
      disease stage, Gleason score and clinical outcome. Clinical followup was 4.3 to
      11.4 years after surgery (median 7.9). RESULTS: Disease did not progress in 17 of
      the 43 cases, while recurrence and/or metastasis developed in the other 26 at a
      median of 6.5 and 6.9 years, respectively. Bone sialoprotein and bone
      morphogenetic protein 6 expression detected in 28 (65%) and 29 (67%) of the 43
      samples, respectively, was significantly associated (p = 0.0001). Thymidine
      phosphorylase detected in 26 samples (60%) was not related to bone sialoprotein
      and/or bone morphogenetic protein 6 positivity. Bone sialoprotein and/or bone
      morphogenetic protein 6 expression correlated with bone metastasis, while
      thymidine phosphorylase expression was related to local recurrence (p = 0.002
      and/or 0.007, and 0.00007, respectively). On multivariate analysis only the
      correlation of thymidine phosphorylase expression with recurrence remained
      statistically significant (p = 0.002). Co-expression of the 3 markers was
      observed in the samples of 10 of the 11 patients (90%) with bone metastases and
      only in 5 of the 17 (29%) who were disease-free. CONCLUSIONS: This study
      indicates that the expression of bone sialoprotein, bone morphogenetic protein 6
      and thymidine phosphorylase determined at a clinically early stage of disease by
      a simple immunohistochemical technique would enable subgroups of patients to be
      identified that are at different risks of bone metastasis or recurrence.
      Detection of such markers would provide additional prognostic information that
      would be useful for patients with intermediate or low Gleason score or stage
      disease. These patients would benefit from a more adapted clinical follow-up.

PMID- 11586263
TI  - Loss of heterozygosity and microsatellite instability at chromosomal sites 1Q and
      10Q in morphologically distinct regions of late stage prostate lesions.
AB  - PURPOSE: We investigated the incidence of loss of heterozygosity (LOH) and
      microsatellite instability in sporadic prostate cancer and surrounding tissue at
      loci encompassing the HPC1 and PTEN genes. MATERIALS AND METHODS: Surgical
      specimens from 63 patients with sporadic stage T3 or T4 prostatic adenocarcinoma
      were analyzed for LOH and microsatellite instability. Microdissected tissue
      included morphologically normal foci, benign prostatic hyperplasia (BPH) and
      prostatic adenocarcinoma. LOH analysis was performed using 4 microsatellite
      markers that map in the region of the 1q24 to 25 locus of the putative prostate
      cancer susceptibility gene HPC1 and 4 that map in the region of the 10q23 locus
      of the PTEN gene. RESULTS: The incidence of LOH on 10q was consistent with that
      previously reported in prostatic tumors. LOH associated with the PTEN locus was
      recorded in morphologically normal foci, BPH and adenocarcinoma. Sequence
      analysis of PTEN in a limited number of lesions revealed mutations in nontumor
      and tumor tissue. Analysis of the DS10215 locus showed significant LOH in tumor
      but not in benign tissue, suggestive of a tumor suppressor gene in this region
      associated with prostatic neoplastic progression. In contrast, no significant LOH
      was observed in the same tissues at 4 loci on chromosome 1q. In this study we
      recorded elevated levels of microsatellite instability in benign prostatic tissue
      with an additional increase associated with prostatic adenocarcinoma.
      CONCLUSIONS: The low incidence of LOH in the region of the HPC1 locus in all
      prostate lesions studied suggests that this putative hereditary prostate cancer
      susceptibility locus does not appear to have a role in sporadic prostate cancer,
      at least not in the context of LOH. In contrast, analysis of the same tissues for
      LOH at chromosome 10q confirmed frequent alterations in this region linked to
      late stage prostate cancer. PTEN mutations in microdissected morphologically
      normal and BPH tissue showed alterations in nontumor tissue surrounding
      adenocarcinoma. Microsatellite instability was increased in adenocarcinomas over
      an elevated background recorded in surrounding tissues.

PMID- 11586264
TI  - Inhibitory effects of digitalis on the proliferation of androgen dependent and
      independent prostate cancer cells.
AB  - PURPOSE: Digitalis or cardiac glycosides have been noted to induce tumor static
      or oncolytic effects in various types of cancer. We evaluated the effects and
      underlying mechanisms of cardiac glycosides, including digoxin, digitoxin and
      ouabain, on the proliferation of hormone dependent and independent prostate
      cancer cell lines. MATERIALS AND METHODS: Cell proliferation of the 3 human
      prostate cancer cell lines LNCaP, DU145 and PC3 was measured by 3-(4,5
      dimethylthiazol-2-yle)2,5-diphenyltetralozium bromide (Sigma Chemical Co., St.
      Louis, Missouri) colorimetric assay. The cytotoxic effects of digitalis on
      prostate cancer cells were determined by lactate dehydrogenase measurements of
      the culture medium. Intracellular Ca2+ was measured by a dual wavelength
      spectrometer system. The percent of apoptotic cells after digitalis treatment was
      measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick end-labeling and flow cytometry. RESULTS: Digoxin, digitoxin
      and ouabain significantly inhibited the proliferation of LNCaP, DU145 and PC3
      cells at a dose of 1 or 10 microM. after 1 to 4 days of culture. Cytotoxicity of
      digitalis on the DU145 and LNCaP cells was dose dependent but cytotoxicity was
      not obvious in PC3. Digitalis (1 microM.) significantly increased intracellular
      Ca2+ in LNCaP and DU145 after 12 hours of culture but PC3 cells needed a 24-hour
      treatment to show any effect. In the apoptosis measurement digitalis at a dose of
      1 and 10 microM. also significantly increased the percent of apoptotic cells in
      the LNCaP, DU145 and PC3 cell lines. Normal control human glomerular epithelial
      cells showed no response to digitalis treatment at all tested doses. CONCLUSIONS:
      Digitalis may inhibit the proliferation of prostate cancer cell lines, although
      the 3 cell lines showed varied sensitivity to digitalis. These effects are
      possibly the result of a mechanism involving sustained elevation of the
      concentration of intracellular Ca2+ and of apoptosis.

PMID- 11586265
TI  - Decreased expression of cellular prostatic acid phosphatase increases
      tumorigenicity of human prostate cancer cells.
AB  - PURPOSE: Understanding cell proliferation regulation in hormone refractory
      prostate cancer may provide answers for novel solutions. Protein tyrosine
      phosphatases have been thought to have key roles in regulating cell proliferation
      and be involved in oncogenesis, although to our knowledge their functional roles
      in human prostate cancer remain unknown. Human prostatic acid phosphatase (PAcP),
      a major phosphatase in prostate epithelium, has been shown to function as a
      neutral protein tyrosine phosphatase in these cells. We evaluated the biological
      significance of cellular prostatic acid phosphatase expression in human prostate
      cancer cells. MATERIALS AND METHODS: Immunohistochemical testing of human
      prostate cancer archival specimens was done to evaluate the expression of
      cellular PAcP. Immunoprecipitation and immunoblotting were performed to determine
      cellular PAcP and SH2 domain-bearing tyrosine phosphatase-1 levels as well as
      tyrosine phosphorylation of c-ErbB-2/neu in different human prostate cancer
      cells. The biological behavior of LNCaP derivative sublines was characterized in
      vitro and in vivo by soft agar analysis and xenograft animal inoculation.
      RESULTS: Immunohistochemical staining of human prostate clearly showed that
      cellular levels of PAcP significantly decreases in prostate cancer cells (p
      <0.001). The results of biochemical characterization revealed that the cellular
      level of PAcP but not SHP-1, another differentiation associated protein tyrosine
      phosphatase, consistently correlated negatively with the growth of several human
      prostate cancer cell lines. Reintroducing cellular PAcP activity in prostate
      cancer cells by PAcP complementary DNA transfection resulted in decreased
      tyrosine phosphorylation of c-ErbB-2/neu, decreased proliferation rates in
      culture as well as decreased anchorage independent growth in soft agar. The
      xenograft animal model demonstrated that a higher tumor growth rate as well as
      larger size is associated with a lower level of cellular PAcP. CONCLUSIONS:
      Cellular PAcP can down-regulate prostate cancer cell growth, at least partially
      by dephosphorylating c-ErbB-2/neu. Therefore, decreased cellular PAcP expression
      in cancer cells may be involved in prostate cancer progression.

PMID- 11586266
TI  - Augmented stretch activated adenosine triphosphate release from bladder
      uroepithelial cells in patients with interstitial cystitis.
AB  - PURPOSE: Extracellular adenosine triphosphate (ATP) has been shown to mediate
      inflammation and nociception and, therefore, it may have a role in symptoms
      associated with interstitial cystitis. We theorized that the bladder
      uroepithelium releases ATP in response to stretch and, furthermore, this process
      is augmented in interstitial cystitis. MATERIALS AND METHODS: We quantitated ATP
      using the luciferin-luciferase assay. Urinary ATP levels were compared in 35
      patients with interstitial cystitis and in 33 normal controls after pH
      correction. Cultured interstitial cystitis and normal urothelial cells from the
      bladder biopsies of 5 patients each were stretched with the Flexcell 2000 machine
      (Flexcell International Corp., McKeesport, Pennsylvania) and supernatant ATP
      concentrations were measured. RESULTS: Mean urinary ATP plus or minus standard
      error of mean was significantly higher in patients with interstitial cystitis
      than in controls (L value 985 +/- 161 versus 377 +/- 27, p = 0.0007). Supernatant
      ATP released by stretched interstitial cystitis cells was stretch intensity
      dependent when comparing 0%, 10% and 20% elongation, and was also significantly
      higher in stretched interstitial cystitis than in stretched normal cells.
      CONCLUSIONS: Adenosine triphosphate was significantly elevated in the urine of
      individuals with interstitial cystitis and the stretch activated release of ATP
      was augmented in interstitial cystitis urothelium. Increased extracellular ATP
      may have a role in mechanosensory transduction and to our knowledge it represents
      a novel hypothesis.

PMID- 11586267
TI  - A new approach to recording the electromyographic activity of detrusor smooth
      muscle.
AB  - PURPOSE: Extracellular recordings from the whole intact mammalian bladder of the
      electrical events leading to contraction of the organ have been elusive for
      almost 50 years despite the widespread potential applications of such a
      technique. The principal problem is the need to isolate the small real signals
      reflecting membrane depolarization from the large electromechanical artifact
      generated as the organ contracts. In this preliminary study we determined whether
      electrical signals may be isolated and verified as biological using extracellular
      bipolar reversible suction electrodes. MATERIALS AND METHODS: Six whole excised
      guinea pig bladders were mounted in an especially constructed organ bath.
      Electrical activity resulting from nerve stimulation of the organ was recorded
      using a novel 10 bipolar Pt/PtCl suction electrode simultaneously with changes in
      intravesical pressure. Mechanical and pharmacological control experiments were
      performed to determine the true origin of these signals. RESULTS: A predominantly
      biphasic electrical signal of a mean amplitude plus or minus standard deviation
      of 647 plus or minus 301 microV. and a mean duration of 293 plus or minus 51
      milliseconds was consistently recorded from the serosal surface of all guinea pig
      bladders. In all cases the electrical signal and mechanical response to
      stimulation were completely abolished by 1 microM. tetrodotoxin. The signal
      always preceded any change in intravesical pressure. It was sensitive to changes
      in the CaCl2 concentration of the superfusate, abolished by purinergic but not
      cholinergic neuromuscular blockade and independent of electromechanical artifact.
      CONCLUSIONS: In this preliminary report we describe a novel technique by which
      nerve mediated detrusor electrical activity leading to contraction of the whole
      intact guinea pig bladder may be isolated from artifact and verified as real. We
      hope that development of this technique may enable its application to the in situ
      human bladder. However, to our knowledge whether electromyographic activity may
      be recorded from human detrusor remains to be determined.

PMID- 11586268
TI  - Effects of the nuclear factor-kappaB inhibitors 2-hydroxy-4
      trifluoromethylbenzoic acid and aspirin on micturition in rats with normal and
      inflamed bladder.
AB  - PURPOSE: We examined the effects of intravenous administration of the 2 nuclear
      factor-kappaB inhibitors aspirin and 2-hydroxy-4-trifluoromethylbenzoic acid
      (HTB) on bladder filling and voiding in anesthetized and conscious rats.
      MATERIALS AND METHODS: Disappearance of isovolumic bladder contractions after
      intravenous administration of different doses of aspirin and HTB in anesthetized,
      transurethrally catheterized rats was evaluated. Cystometry was performed in
      conscious rats during bladder infusion with saline or diluted acetic acid as well
      as in those with cyclophosphamide induced cystitis. Changes in bladder capacity
      and voiding pressure were evaluated after intravenous administration of test
      compounds. RESULTS: Aspirin induced a dose dependent disappearance of isovolumic
      bladder contractions in anesthetized rats with an extrapolated dose of 2.1
      mg./kg. inducing 10 minutes of bladder quiescence. HTB was practically inactive,
      inducing a dose independent block of 3 to 4 minutes after intravenous
      administration of 1 to 10 mg./kg. In conscious rats with a bladder infused with
      saline aspirin was poorly active on bladder capacity, inducing a 20% increase 60
      minutes after intravenous administration of 30 and 100 mg./kg. In rats with a
      bladder infused with acetic acid aspirin was much more active when injected at
      the initiation of inflammation and after 1 hour of irritant infusion. In this
      latter situation aspirin increased bladder capacity up to 60% after intravenous
      administration of 30 and 100 mg./kg. Similar results were obtained in rats with
      cyclophosphamide induced cystitis in which the bladder was infused with saline.
      In these cystometrography models 30 mg./kg. HTB intravenously was completely
      inactive. CONCLUSIONS: The results show that HTB is devoid of significant effects
      on the micturition reflex in the absence or presence of bladder inflammation,
      suggesting that acute inhibition of nuclear factor-kappaB does not influence
      bladder urodynamics in rats. In contrast, aspirin, which is a cyclooxygenase and
      nuclear factor-kappaB inhibitor, was always effective, indicating the important
      role of cyclooxygenase enzymes.

PMID- 11586269
TI  - Inhibition of the contractile responses of isolated human and rat bladders by
      clenbuterol.
AB  - PURPOSE: We investigated the inhibition of the contractile responses of human
      continent and unstable detrusor muscle by the beta2 agonist clenbuterol as well
      as the inhibition of electrical field stimulation evoked contractile responses of
      isolated rat bladder muscle strips by orally administered clenbuterol. MATERIALS
      AND METHODS: The contractile responses of human continent and unstable detrusor
      muscle strips to electrical field stimulation (0.05 milliseconds, 0.5 to 80 Hz.)
      were measured before and after adding 10(-9) to 10(-4) M. clenbuterol in vitro.
      In addition, 6 rats per group were dosed orally with 2 microg x kg(-1)
      clenbuterol daily acutely (1 dose) or chronically (1 dose daily for 8 days), or
      with distilled water to serve as controls. The contractile response to electrical
      field stimulation of strips of isolated detrusor muscle was then measured. Serum
      clenbuterol levels were analyzed in duplicate by enzyme-linked immunosorbent
      assay and high performance liquid chromatography. RESULTS: In vitro clenbuterol
      significantly inhibited the electrical field stimulation evoked contractile
      responses of detrusor muscle strips from unstable but not continent human
      bladders. A significant inhibitory effect of clenbuterol on the electrical field
      stimulation evoked contractile response of rat detrusor muscle was observed after
      chronic but not acute oral dosing (p <0.01). Serum clenbuterol levels measured by
      enzyme-linked immunosorbent assay and high performance liquid chromatography were
      not significantly different. CONCLUSIONS: Clenbuterol or related beta2
      adrenoceptor agonists may represent a useful therapeutic strategy for detrusor
      muscle overactivity.

PMID- 11586272
TI  - Ensuring the pathogen safety of intravenous immunoglobulin and other human plasma
      derived therapeutic proteins.
AB  - Countless patients and clinicians rely on therapeutic proteins, such as
      intravenous immunoglobulins (IVIGs), isolated from human blood plasma. Since
      plasma is predisposed to contamination by a variety of blood-borne pathogens,
      ascertaining and ensuring the pathogen safety of plasma-derived therapeutics is a
      priority among manufacturers. Even though the pathogen safety records for IVIG
      and other plasma proteins are excellent, the industry remains active in research
      programs aimed at improving the margin of safety. Industry initiatives designed
      to increase the safety of plasma-derived products range from donor screening and
      testing to implementing methods into the manufacturing processes that can
      inactivate or remove pathogens from product streams. In general, the industry's
      comprehensive strategy is designed to provide patients and caregivers with the
      safest plasma products possible.

PMID- 11586273
TI  - Fc gamma RIIB as a potential molecular target for intravenous gamma globulin
      therapy.
AB  - The ability of the immune system to respond appropriately to foreign antigen is
      dependent on a delicate balance of activating and inhibitory signals. Recently,
      the role of cell surface inhibitory receptors in attenuating immune responses,
      thereby preventing pathologic conditions including autoimmunity and atopy, has
      been recognized. It is postulated that the beneficial effects of intravenous
      gamma globulin in the treatment of immune disorders may be attributable, at least
      in part, to engagement of Fc gamma RIIB, a member of the recently described
      family of immune inhibitory receptors. Recent genetic and biochemical studies
      have identified the SH2 domain-containing inositol 5-phosphatase (SHIP) as a
      critical effector in Fc gamma RIIB inhibitory signaling. This review summarizes
      recent work from our laboratory and others aimed to define the mechanism(s) by
      which Fc gamma RIIB and its effector, SHIP, inhibit immune responses. Elucidation
      of these mechanisms may lead to the development of therapeutic strategies for the
      treatment of autoimmune and inflammatory pathologies that specifically target Fc
      gamma RIIB or its effector(s).

PMID- 11586274
TI  - How cells die: apoptosis pathways.
AB  - Generally speaking, there are 2 types of cell death: apoptosis and necrosis.
      Necrotic cell death is considered an accidental type of death, caused by gross
      cell injury, and results in the death of groups of cells within a tissue. In
      contrast, apoptotic cell death may be induced or is preprogrammed into the cell
      (eg, during development) and results in the death of the individual cells.
      Apoptotic cells may be characterized by specific morphologic and biochemical
      changes orchestrated by a family of cysteine proteases known as caspases. At the
      molecular level, apoptosis is tightly regulated. There are 2 main pathways to
      apoptotic cell death. One involves the interaction of a death receptor, such as
      the TNF receptor-1 or the Fas receptor with its ligand, and the second pathway
      depends on the participation of mitochondria. Proapoptotic and antiapoptotic
      members of the Bcl-2 family regulate the mitochondrial pathway. The end result of
      either pathway is caspase activation and the cleavage of specific cellular
      substrates, resulting in the morphologic and biochemical changes associated with
      the apoptotic phenotype.

PMID- 11586275
TI  - Activation of toll-like receptors by microbial lipoproteins: role in host
      defense.
AB  - Conserved throughout evolution, mammalian toll-like receptors (TLRs) participate
      in innate immune response to microbial pathogens. The TLRs mediate activation by
      microbial ligands, resulting in cytokine activation as well as other host defense
      mechanisms. Activation of TLRs also can result in tissue injury including
      manifestations of septic shock and host cell apoptosis. In this manner, the
      activation of mammalian TLRs in the context of infectious disease can contribute
      to host defense and immunopathology.

PMID- 11586276
TI  - Use of intravenous immunoglobulin in the treatment of staphylococcal and
      streptococcal toxic shock syndromes and related illnesses.
AB  - Pyrogenic toxin superantigens comprise a large family of exotoxins made by
      Staphylococcus aureus and group A streptococci. These toxins include toxic shock
      syndrome toxin-1, the staphylococcal enterotoxins, and the streptococcal
      pyrogenic exotoxins (synonyms: scarlet fever toxins and erythrogenic toxins), all
      of which have the ability to cause toxic shock syndromes and related illnesses.
      These toxins have a similar three-dimensional structure that allows them to
      interact with relatively invariant regions of major histocompatibility complex
      class II molecules on the surface of antigen-presenting cells and with certain
      variable regions of the T-cell receptor-beta chain. The consequence of these
      interactions (and other immunobiological properties of the toxins) is the
      exaggerated release of bioactive cytokines. The latter molecules are responsible
      for the clinical signs of illness associated with these toxins.

PMID- 11586277
TI  - Antibody-directed therapy: past, present, and future.
AB  - Antibody-based therapy, which is the administration of polyclonal, hyperimmune,
      or monoclonal antibodies, has emerged as an important therapeutic approach in a
      wide variety of diseases. Polyclonal intravenous immunoglobulin became available
      in the early 1980s and supplanted intramuscular IgG in the treatment of antibody
      deficiency diseases. During the last 2 decades, intravenous immunoglobulin has
      shown potent immunomodulatory and anti-inflammatory effects in many diseases.
      Whether these effects are mediated through specific antibody or Fc-receptor
      interactions is unclear. This review examines some of the current and future
      prospects for antibody-based therapy.

PMID- 11586278
TI  - Overview of infections and cardiovascular diseases.
AB  - Microbes have been proposed as inciting agents of tissue injury and inflammation,
      both of which underlie the pathogenesis of atherosclerosis. Viruses, including
      the herpes simplex virus and cytomegalovirus, as well as bacteria such as
      Chlamydia pneumoniae, have been implicated in the process. In vitro, these agents
      promote a proinflammatory and a procoagulant phenotype in vascular cells. Viruses
      augment cell accumulation through alterations of apoptosis. Infectious agents may
      play a role in pathogenesis of atherosclerosis by triggering an autoimmune
      response due to microbial molecular mimicry. It is unlikely that a single agent
      is the sole cause or modulator of this heterogeneous disease. Contradictory
      epidemiological studies may be reconciled with a new construct suggesting that
      multiple pathogens infecting an individual in aggregate may promote an
      inflammatory and procoagulant environment that underlies the pathogenesis of
      atherosclerosis.

PMID- 11586279
TI  - Immunoglobulin-mediated CNS repair.
AB  - Our view of the immune system continues to evolve from a system dedicated
      primarily to defense against pathogens to a system that monitors the integrity of
      the organism and aids in repair following damage. Repair following injury to the
      central nervous system (CNS) is facilitated by both cellular and humoral
      components of the immune system. Transfer of macrophages or T cells activated
      against CNS antigens promote axon regrowth and protect axons from further damage.
      Animals immunized with spinal cord antigens and subsequently challenged with
      demyelination or transection of the spinal cord demonstrate better repair than
      animals without prior immunization. In both experimental systems, antibodies are
      the biologically active immune component. Human mAbs reactive to oligodendrocytes
      that arise in the absence of neurologic injury promote remyelination. These data
      support the hypothesis that B-cell clones producing mAbs reactive to CNS epitopes
      are a normal part of the human antibody repertoire. They challenge the assertion
      that an immune response to CNS antigens is pathogenic. Treatment with CNS
      reactive human mAbs following CNS disease may facilitate CNS regeneration.

PMID- 11586280
TI  - Use of intravenous gamma globulins in neuroimmunologic diseases.
AB  - Intravenous gamma globulin (IVIg) is used in the treatment of immunologic
      diseases that affect the entire neuroaxis, including the brain, spinal cord,
      peripheral nerves, muscles, and neuromuscular junction. The panel reviewed the
      available literature on the use of IVIg in order to evaluate the efficacy of this
      therapy in neuroimmunologic diseases. In prospective, rigorously controlled,
      double-blinded clinical trials, IVIg was found to have proven efficacy in the
      Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy,
      multifocal motor neuropathy, dermatomyositis, and Lambert-Eaton myasthenic
      syndrome. It was found to be probably effective in myasthenia gravis and
      polymyositis, and possibly effective in several other neuroimmunologic diseases.
      Further studies are needed to evaluate the use of IVIg for neuroimmunologic
      diseases in which its efficacy is suspected but not proven and to elucidate its
      mechanisms of action.

PMID- 11586281
TI  - Obstetric uses of intravenous immunoglobulin: successes, failures, and promises.
AB  - Intravenous immune globulin (IVIG) is approved for use in a number of conditions
      that may occur in obstetrical patients, including autoimmune thrombocytopenia and
      immune deficiency syndromes. IVIG also is widely used in obstetrics for
      nonapproved indications, such as fetal-neonatal alloimmune thrombocytopenia,
      antiphospholipid syndrome, and recurrent miscarriage. This review critically
      analyzes the use of IVIG for these indications based on the best available
      information. The authors conclude IVIG is effective in the management of fetal
      neonatal alloimmune thrombocytopenia. IVIG appears promising as a treatment for
      severe fetal-neonatal alloimmune hemolysis due to antierythrocyte antibodies. A
      prospective multicenter trial should be undertaken. IVIG is no more effective
      than heparin and low-dose aspirin in the treatment of pregnancies complicated by
      antiphospholipid syndrome but has not been adequately evaluated in refractory
      cases. Finally, pending convincing studies, IVIG is not effective and should not
      be used for the management of recurrent miscarriage.

PMID- 11586282
TI  - Intravenous immunoglobulin consensus statement.
AB  - Intravenous immunoglobulin (IVIG) preparations are a mainstay for a number of
      disorders that include primary immuno-deficiency, acute inflammatory conditions,
      hematological disorders, infections, and neuroimmunological disorders. The range
      of therapeutic activity is attributed to IVIG's myriad action mechanisms. IVIG
      can interact and bind onto complement factors, which can prevent complement
      mediated tissue damage, modulate T-lymphocytes, alter cytokine profiles, and
      modulate the immune system. These interactions can act alone or in combination to
      maintain immune balance while preserving homeostasis. A consensus panel was
      convened in 2000 to evaluate and define new advances in IVIG therapies.

PMID- 11586283
TI  - Stem-cell politics.

PMID- 11586285
TI  - Genetic inroads in familial ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease causing
      cell death of motor neurons and progressive muscle weakness. The disease is
      familial in ten percent of cases, of which one-fifth are due to mutations in the
      gene encoding Cu/Zn superoxide dismutase (SOD1). Two papers in this issue of
      Nature Genetics describe homozygous mutations in a new gene on chromosome 2q33 in
      4 families of Arabian origin with a rare form of juvenile onset ALS (ALS2). The
      predicted protein structure has domains homologous to GTPase regulatory proteins,
      and both the types of mutation and the pattern of inheritance suggest that motor
      neuron degeneration is the result of a loss of function. Further work will
      determine the relevance of this breakthrough to other, more common forms of ALS.

PMID- 11586286
TI  - The promoter connection.
AB  - The availability of the complete genomic sequence of yeast now enables
      elucidation of molecular mechanisms governing gene expression patterns. New
      results from the yeast genome and recent advances in predicting and finding human
      promoters support the use of similar combinatorial approaches to study genome
      wide transcriptional regulation in humans.

PMID- 11586287
TI  - The adaptable lin-39.
AB  - Comparative studies of nematode development provide a powerful framework for
      investigating the evolution of developmental mechanisms. A recent report also
      demonstrates how comparative work can inform our understanding of basic
      developmental signaling pathways. In particular, investigation of the differences
      in vulva development between Caenorhabditis elegans and Pristionchus pacificus
      has clarified the molecular relationship between an epidermal growth factor-Ras
      MAP kinase signaling pathway and downstream Hox transcription factor activity.

PMID- 11586288
TI  - Time for T.
AB  - Genetic defects responsible for cleft lip and cleft palate are only now beginning
      to be uncovered. Mutations in the gene encoding a T-box transcription factor have
      been identified as the cause of the rare X-linked syndrome cleft palate with
      tongue-tie. And in another study, heterozygotes for a defective allele for a cell
      adhesion molecule, which is responsible for a rare clefting syndrome when
      homozygous, have been found at higher than expected incidence in sporadic forms
      of clefting.

PMID- 11586289
TI  - Islands of linkage disequilibrium.
AB  - A detailed knowledge of patterns of linkage disequilibrium in human populations
      is widely seen as a prerequisite for effective population-based disease gene
      mapping. New data suggest that linkage disequilibrium is highly structured into
      discrete blocks of sequence separated by hot spots of recombination.

PMID- 11586292
TI  - TGF-beta signaling in tumor suppression and cancer progression.
AB  - Epithelial and hematopoietic cells have a high turnover and their progenitor
      cells divide continuously, making them prime targets for genetic and epigenetic
      changes that lead to cell transformation and tumorigenesis. The consequent
      changes in cell behavior and responsiveness result not only from genetic
      alterations such as activation of oncogenes or inactivation of tumor suppressor
      genes, but also from altered production of, or responsiveness to, stimulatory or
      inhibitory growth and differentiation factors. Among these, transforming growth
      factor beta (TGF-beta) and its signaling effectors act as key determinants of
      carcinoma cell behavior. The autocrine and paracrine effects of TGF-beta on tumor
      cells and the tumor micro-environment exert both positive and negative influences
      on cancer development. Accordingly, the TGF-beta signaling pathway has been
      considered as both a tumor suppressor pathway and a promoter of tumor progression
      and invasion. Here we evaluate the role of TGF-beta in tumor development and
      attempt to reconcile the positive and negative effects of TGF-beta in
      carcinogenesis.

PMID- 11586293
TI  - Intra-cytoplasmic sperm injection and infertility.

PMID- 11586294
TI  - An SSLP marker-anchored BAC framework map of the mouse genome.
AB  - We have constructed a BAC framework map of the mouse genome consisting of 2,808
      PCR-confirmed BAC clusters, using a previously described method. Fingerprints of
      BACs from selected clusters confirm the accuracy of the map. Combined with BAC
      fingerprint data, the framework map covers 37% of the mouse genome.

PMID- 11586295
TI  - A role for MLH3 in hereditary nonpolyposis colorectal cancer.
AB  - We investigated a possible role of the mismatch-repair gene MLH3 in hereditary
      nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and
      in 288 patients suspected of having HNPCC. We identified ten different germline
      MLH3 variants, one frameshift and nine missense mutations, in 12 patients
      suspected of HNPCC. Three of the 12 also carried a mutation in MSH6.

PMID- 11586296
TI  - Unexpectedly high rate of de novo constitutional t(11;22) translocations in sperm
      from normal males.
AB  - Junction fragments from the constitutional t(11;22)(q23;q11) translocation have
      previously been cloned and sequenced. Here we report a high incidence of
      translocation-specific PCR products in sperm DNA from normal individuals. Somatic
      DNA from these and other normal individuals or from people with chromosomal
      breakage syndromes do not yield PCR junction fragments, indicating that this
      translocation originates during meiosis.

PMID- 11586297
TI  - The gene encoding alsin, a protein with three guanine-nucleotide exchange factor
      domains, is mutated in a form of recessive amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are
      neurodegenerative conditions that affect large motor neurons of the central
      nervous system. We have identified a familial juvenile PLS (JPLS) locus
      overlapping the previously identified ALS2 locus on chromosome 2q33. We report
      two deletion mutations in a new gene that are found both in individuals with ALS2
      and those with JPLS, indicating that these conditions have a common genetic
      origin. The predicted sequence of the protein (alsin) may indicate a mechanism
      for motor-neuron degeneration, as it may include several cell-signaling motifs
      with known functions, including three associated with guanine-nucleotide exchange
      factors for GTPases (GEFs).

PMID- 11586298
TI  - A gene encoding a putative GTPase regulator is mutated in familial amyotrophic
      lateral sclerosis 2.
AB  - Amyotrophic lateral sclerosis 2 (ALS2) is an autosomal recessive form of juvenile
      ALS and has been mapped to human chromosome 2q33. Here we report the
      identification of two independent deletion mutations linked to ALS2 in the coding
      exons of the new gene ALS2. These deletion mutations result in frameshifts that
      generate premature stop codons. ALS2 is expressed in various tissues and cells,
      including neurons throughout the brain and spinal cord, and encodes a protein
      containing multiple domains that have homology to RanGEF as well as RhoGEF.
      Deletion mutations are predicted to cause a loss of protein function, providing
      strong evidence that ALS2 is the causative gene underlying this form of ALS.

PMID- 11586299
TI  - Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by
      mutations in a new HIT superfamily gene.
AB  - Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative
      disease among Europeans and people of European descent, is characterized by an
      early onset (usually before the age of 25), progressive ataxia, sensory loss,
      absence of tendon reflexes and pyramidal weakness of the legs. We have recently
      identified a unique group of patients whose clinical presentations are
      characterized by autosomal recessive inheritance, early age of onset, FRDA-like
      clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however,
      was excluded. Given the similarities of the clinical presentations to those of
      the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome
      9p13, we confirmed that the disorder of our patients is also linked to the same
      locus. We narrowed the candidate region and have identified a new gene encoding a
      member of the histidine triad (HIT) superfamily as the 'causative' gene. We have
      called its product aprataxin; the gene symbol is APTX. Although many HIT proteins
      have been identified, aprataxin is the first to be linked to a distinct
      phenotype.

PMID- 11586300
TI  - The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein
      aprataxin.
AB  - The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920) is the most
      frequent cause of autosomal recessive ataxia in Japan and is second only to
      Friedreich ataxia in Portugal. It shares several neurological features with
      ataxia-telangiectasia, including early onset ataxia, oculomotor apraxia and
      cerebellar atrophy, but does not share its extraneurological features (immune
      deficiency, chromosomal instability and hypersensitivity to X-rays). AOA1 is also
      characterized by axonal motor neuropathy and the later decrease of serum albumin
      levels and elevation of total cholesterol. We have identified the gene causing
      AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new,
      ubiquitously expressed protein that we named aprataxin. This protein is composed
      of three domains that share distant homology with the amino-terminal domain of
      polynucleotide kinase 3'- phosphatase (PNKP), with histidine-triad (HIT) proteins
      and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is involved in
      DNA single-strand break repair (SSBR) following exposure to ionizing radiation
      and reactive oxygen species. Fragile-HIT proteins (FHIT) cleave diadenosine
      tetraphosphate, which is potentially produced during activation of the SSBR
      complex. The results suggest that aprataxin is a nuclear protein with a role in
      DNA repair reminiscent of the function of the protein defective in ataxia
      telangiectasia, but that would cause a phenotype restricted to neurological signs
      when mutant.

PMID- 11586301
TI  - A radiation hybrid transcript map of the mouse genome.
AB  - Expressed-sequence tag (EST) maps are an adjunct to sequence-based analytical
      methods of gene detection and localization for those species for which such data
      are available, and provide anchors for high-density homology and orthology
      mapping in species for which large-scale sequencing has yet to be done. Species
      for which radiation hybrid-based transcript maps have been established include
      human, rat, mouse, dog, cat and zebrafish. We have established a comprehensive
      first-generation-placement radiation hybrid map of the mouse consisting of 5,904
      mapped markers (3,993 ESTs and 1,911 sequence-tagged sites (STSs)). The mapped
      ESTs, which often originate from small-EST clusters, are enriched for genes
      expressed during early mouse embryogenesis and are probably different from those
      localized in humans. We have confirmed by in situ hybridization that even
      singleton ESTs, which are usually not retained for mapping studies, may represent
      bona fide transcribed sequences. Our studies on mouse chromosomes 12 and 14
      orthologous to human chromosome 14 show the power of our radiation hybrid map as
      a predictive tool for orthology mapping in humans.

PMID- 11586302
TI  - A radiation hybrid map of mouse genes.
AB  - A comprehensive gene-based map of a genome is a powerful tool for genetic studies
      and is especially useful for the positional cloning and positional candidate
      approaches. The availability of gene maps for multiple organisms provides the
      foundation for detailed conserved-orthology maps showing the correspondence
      between conserved genomic segments. These maps make it possible to use cross
      species information in gene hunts and shed light on the evolutionary forces that
      shape the genome. Here we report a radiation hybrid map of mouse genes, a
      combined project of the Whitehead Institute/Massachusetts Institute of Technology
      Center for Genome Research, the Medical Research Council UK Mouse Genome Centre,
      and the National Center for Biotechnology Information. The map contains 11,109
      genes, screened against the T31 RH panel and positioned relative to a reference
      map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to
      the human genome sequence and provides a framework for overlaying the human
      genome sequence to the mouse and for sequencing the mouse genome.

PMID- 11586303
TI  - Intensely punctate meiotic recombination in the class II region of the major
      histocompatibility complex.
AB  - There is considerable interest in understanding patterns of linkage
      disequilibrium (LD) in the human genome, to aid investigations of human evolution
      and facilitate association studies in complex disease. The relative influences of
      meiotic crossover distribution and population history on LD remain unclear,
      however. In particular, it is uncertain to what extent crossovers are clustered
      into 'hot spots, that might influence LD patterns. As a first step to
      investigating the relationship between LD and recombination, we have analyzed a
      216-kb segment of the class II region of the major histocompatibility complex
      (MHC) already characterized for familial crossovers. High-resolution LD analysis
      shows the existence of extended domains of strong association interrupted by
      patchwork areas of LD breakdown. Sperm typing shows that these areas correspond
      precisely to meiotic crossover hot spots. All six hot spots defined share a
      remarkably similar symmetrical morphology but vary considerably in intensity, and
      are not obviously associated with any primary DNA sequence determinants of hot
      spot activity. These hot spots occur in clusters and together account for almost
      all crossovers in this region of the MHC. These data show that, within the MHC at
      least, crossovers are far from randomly distributed at the molecular level and
      that recombination hot spots can profoundly affect LD patterns.

PMID- 11586304
TI  - Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to
      Crohn disease.
AB  - Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure
      localization of rare disease genes, but has not yet been widely applied to common
      disease. We sought to design a systematic approach for LD mapping and apply it to
      the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The
      key issues are: (i) to detect a significant LD signal (ii) to rigorously bound
      the critical region and (iii) to identify the causal genetic variant within this
      region. We previously mapped the IBD5 locus to a large region spanning 18 cM of
      chromosome 5q31 (P<10(-4)). Using dense genetic maps of microsatellite markers
      and single-nucleotide polymorphisms (SNPs) across the entire region, we found
      strong evidence of LD. We bound the region to a common haplotype spanning 250 kb
      that shows strong association with the disease (P< 2 x 10(-7)) and contains the
      cytokine gene cluster. This finding provides overwhelming evidence that a
      specific common haplotype of the cytokine region in 5q31 confers susceptibility
      to Crohn disease. However, genetic evidence alone is not sufficient to identify
      the causal mutation within this region, as strong LD across the region results in
      multiple SNPs having equivalent genetic evidence-each consistent with the
      expected properties of the IBD5 locus. These results have important implications
      for Crohn disease in particular and LD mapping in general.

PMID- 11586305
TI  - High-resolution haplotype structure in the human genome.
AB  - Linkage disequilibrium (LD) analysis is traditionally based on individual genetic
      markers and often yields an erratic, non-monotonic picture, because the power to
      detect allelic associations depends on specific properties of each marker, such
      as frequency and population history. Ideally, LD analysis should be based
      directly on the underlying haplotype structure of the human genome, but this
      structure has remained poorly understood. Here we report a high-resolution
      analysis of the haplotype structure across 500 kilobases on chromosome 5q31 using
      103 single-nucleotide polymorphisms (SNPs) in a European-derived population. The
      results show a picture of discrete haplotype blocks (of tens to hundreds of
      kilobases), each with limited diversity punctuated by apparent sites of
      recombination. In addition, we develop an analytical model for LD mapping based
      on such haplotype blocks. If our observed structure is general (and published
      data suggest that it may be), it offers a coherent framework for creating a
      haplotype map of the human genome.

PMID- 11586307
TI  - Industrial 'R' up in a downturn.

PMID- 11586306
TI  - Haplotype tagging for the identification of common disease genes.
AB  - Genome-wide linkage disequilibrium (LD) mapping of common disease genes could be
      more powerful than linkage analysis if the appropriate density of polymorphic
      markers were known and if the genotyping effort and cost of producing such an LD
      map could be reduced. Although different metrics that measure the extent of LD
      have been evaluated, even the most recent studies have not placed significant
      emphasis on the most informative and cost-effective method of LD mapping-that
      based on haplotypes. We have scanned 135 kb of DNA from nine genes, genotyped 122
      single-nucleotide polymorphisms (SNPs; approximately 184,000 genotypes) and
      determined the common haplotypes in a minimum of 384 European individuals for
      each gene. Here we show how knowledge of the common haplotypes and the SNPs that
      tag them can be used to (i) explain the often complex patterns of LD between
      adjacent markers, (ii) reduce genotyping significantly (in this case from 122 to
      34 SNPs), (iii) scan the common variation of a gene sensitively and
      comprehensively and (iv) provide key fine-mapping data within regions of strong
      LD. Our results also indicate that, at least for the genes studied here, the
      current version of dbSNP would have been of limited utility for LD mapping
      because many common haplotypes could not be defined. A directed re-sequencing
      effort of the approximately 10% of the genome in or near genes in the major
      ethnic groups would aid the systematic evaluation of the common variant model of
      common disease.

PMID- 11586308
TI  - Large Hadron Collider in crisis as magnet costs spiral upwards.

PMID- 11586309
TI  - Senators call for biodefence boost.

PMID- 11586310
TI  - Bilateral Vietnam study plans to assess war fallout of dioxin.

PMID- 11586313
TI  - Testing time for gene patent as Europe rebels.

PMID- 11586312
TI  - Doctors propose panel on research misconduct.

PMID- 11586314
TI  - Last-minute floods sink research.

PMID- 11586315
TI  - Mouse genome roars ahead with new map.

PMID- 11586316
TI  - Psychiatrist launches lawsuit over 'academic freedom'.

PMID- 11586317
TI  - NASA budget problems alarm space-station collaborators.

PMID- 11586318
TI  - Vatican approves use of animal transplants 'to benefit humans'.

PMID- 11586321
TI  - Hard times for high tech.

PMID- 11586322
TI  - Biologists join the dots.

PMID- 11586323
TI  - Rules on originality need to be clearly set out.

PMID- 11586324
TI  - Related problems.

PMID- 11586325
TI  - Give us time to put reforms into action.

PMID- 11586334
TI  - Tales behind the tags.

PMID- 11586326
TI  - In the stem-cell debate, new concepts need new words.

PMID- 11586335
TI  - The natural economy.

PMID- 11586336
TI  - Talk of genetics and vice versa.

PMID- 11586337
TI  - Bose-Einstein condensates. Mastering the language of atoms.

PMID- 11586338
TI  - Bacterial genomics. A plague o' both your hosts.

PMID- 11586340
TI  - Global change. Chill taken out of the tropics.

PMID- 11586341
TI  - Neurobiology. Developing order.

PMID- 11586343
TI  - Acoustic physics. Suspended by sound.

PMID- 11586344
TI  - Human genetics. To clot or not.

PMID- 11586346
TI  - Snapping shrimp make flashing bubbles.
AB  - Snapping shrimp produce a loud crackling noise that is intense enough to disturb
      underwater communication. This sound originates from the violent collapse of a
      large cavitation bubble generated under the tensile forces of a high-velocity
      water jet formed when the shrimp's snapper-claw snaps shut (Fig. 1). Here we show
      that a short, intense flash of light is emitted as the bubble collapses,
      indicating that extreme pressures and temperatures of at least 5,000 K (ref. 4)
      must exist inside the bubble at the point of collapse. We have dubbed this
      phenomenon 'shrimpoluminescence' - the first observation, to our knowledge, of
      this mode of light production in any animal - because of its apparent similarity
      to sonoluminescence, the light emission from a bubble periodically driven by
      ultrasound.

PMID- 11586347
TI  - Carbon emissions. The economic benefits of the Kyoto Protocol.
AB  - The third Conference of the Parties in Kyoto set the target of reducing
      greenhouse-gas emissions by an average of 5.3% with respect to 1990 values by
      2008-2012. One of the main objections to the protocol's ratification is that
      compliance would pose an unbearable economic burden on the countries involved.
      But we show here that this is not the case if costs apart from the direct costs
      of energy production are also considered. Costs are also incurred in rectifying
      damage to human health, material goods, agriculture and the environment related
      to greenhouse-gas emissions.

PMID- 11586348
TI  - Palaeolithic paintings. Evolution of prehistoric cave art.
AB  - Sophisticated examples of European palaeolithic parietal art can be seen in the
      caves of Altamira, Lascaux and Niaux near the Pyrenees, which date to the
      Magdalenian period (12,000-17,000 years ago), but paintings of comparable skill
      and complexity were created much earlier, some possibly more than 30,000 years
      ago. We have derived new radiocarbon dates for the drawings that decorate the
      Chauvet cave in Vallon-Pont-d'Arc, Ardeche, France, which confirm that even
      30,000 years ago Aurignacian artists, already known as accomplished carvers,
      could create masterpieces comparable to the best Magdalenian art. Prehistorians,
      who have traditionally interpreted the evolution of prehistoric art as a steady
      progression from simple to more complex representations, may have to reconsider
      existing theories of the origins of art.

PMID- 11586349
TI  - Physiology. Cold current in thermoreceptive neurons.
AB  - We sense the temperature of our skin and surroundings using specific
      thermoreceptors, which are sensitive to cold and warmth, but little is known
      about how these receptors transduce temperature into electrical activity. We have
      discovered an inward ionic current that is activated by moderate cooling in a
      small number of rat sensory neurons. This current has features that are found in
      intact cold receptors, including sensitization by menthol, adaptation upon
      sustained cooling, and modulation by calcium, and is likely to be important in
      cold sensing.

PMID- 11586350
TI  - Warm tropical sea surface temperatures in the Late Cretaceous and Eocene epochs.
AB  - Climate models with increased levels of carbon dioxide predict that global
      warming causes heating in the tropics, but investigations of ancient climates
      based on palaeodata have generally indicated cool tropical temperatures during
      supposed greenhouse episodes. For example, in the Late Cretaceous and Eocene
      epochs there is abundant geological evidence for warm, mostly ice-free poles, but
      tropical sea surface temperatures are generally estimated to be only 15-23
      degrees C, based on oxygen isotope palaeothermometry of surface-dwelling
      planktonic foraminifer shells. Here we question the validity of most such data on
      the grounds of poor preservation and diagenetic alteration. We present new data
      from exceptionally well preserved foraminifer shells extracted from impermeable
      clay-rich sediments, which indicate that for the intervals studied, tropical sea
      surface temperatures were at least 28-32 degrees C. These warm temperatures are
      more in line with our understanding of the geographical distributions of
      temperature-sensitive fossil organisms and the results of climate models with
      increased CO2 levels.

PMID- 11586351
TI  - Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic
      purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a life-threatening systemic illness
      of abrupt onset and unknown cause. Proteolysis of the blood-clotting protein von
      Willebrand factor (VWF) observed in normal plasma is decreased in TTP patients.
      However, the identity of the responsible protease and its role in the
      pathophysiology of TTP remain unknown. We performed genome-wide linkage analysis
      in four pedigrees of humans with congenital TTP and mapped the responsible
      genetic locus to chromosome 9q34. A predicted gene in the identified interval
      corresponds to a segment of a much larger transcript, identifying a new member of
      the ADAMTS family of zinc metalloproteinase genes (ADAMTS13). Analysis of
      patients' genomic DNA identified 12 mutations in the ADAMTS13 gene, accounting
      for 14 of the 15 disease alleles studied. We show that deficiency of ADAMTS13 is
      the molecular mechanism responsible for TTP, and suggest that physiologic
      proteolysis of VWF and/or other ADAMTS13 substrates is required for normal
      vascular homeostasis.

PMID- 11586352
TI  - Light interference from single atoms and their mirror images.
AB  - A single atom emitting single photons is a fundamental source of light. But the
      characteristics of this light depend strongly on the environment of the atom. For
      example, if an atom is placed between two mirrors, both the total rate and the
      spectral composition of the spontaneous emission can be modified. Such effects
      have been observed using various systems: molecules deposited on mirrors, dye
      molecules in an optical cavity, an atom beam traversing a two-mirror optical
      resonator, single atoms traversing a microwave cavity and a single trapped
      electron. A related and equally fundamental phenomenon is the optical interaction
      between two atoms of the same kind when their separation is comparable to their
      emission wavelength. In this situation, light emitted by one atom may be
      reabsorbed by the other, leading to cooperative processes in the emission. Here
      we observe these phenomena with high visibility by using one or two single
      atom(s), a collimating lens and a mirror, and by recording the individual photons
      scattered by the atom(s). Our experiments highlight the intimate connection
      between one-atom and two-atom effects, and allow their continuous observation
      using the same apparatus.

PMID- 11586353
TI  - Bose-Einstein condensation on a microelectronic chip.
AB  - Although Bose-Einstein condensates of ultracold atoms have been experimentally
      realizable for several years, their formation and manipulation still impose
      considerable technical challenges. An all-optical technique that enables faster
      production of Bose-Einstein condensates was recently reported. Here we
      demonstrate that the formation of a condensate can be greatly simplified using a
      microscopic magnetic trap on a chip. We achieve Bose-Einstein condensation inside
      the single vapour cell of a magneto-optical trap in as little as 700 ms-more than
      a factor of ten faster than typical experiments, and a factor of three faster
      than the all-optical technique. A coherent matter wave is emitted normal to the
      chip surface when the trapped atoms are released into free fall; alternatively,
      we couple the condensate into an 'atomic conveyor belt', which is used to
      transport the condensed cloud non-destructively over a macroscopic distance
      parallel to the chip surface. The possibility of manipulating laser-like coherent
      matter waves with such an integrated atom-optical system holds promise for
      applications in interferometry, holography, microscopy, atom lithography and
      quantum information processing.

PMID- 11586354
TI  - Spatially resolved electronic structure inside and outside the vortex cores of a
      high-temperature superconductor.
AB  - Puzzling aspects of high-transition-temperature (high-Tc) superconductors include
      the prevalence of magnetism in the normal state and the persistence of
      superconductivity in high magnetic fields. Superconductivity and magnetism
      generally are thought to be incompatible, based on what is known about
      conventional superconductors. Recent results, however, indicate that
      antiferromagnetism can appear in the superconducting state of a high-Tc
      superconductor in the presence of an applied magnetic field. Magnetic fields
      penetrate a superconductor in the form of quantized flux lines, each of which
      represents a vortex of supercurrents. Superconductivity is suppressed in the core
      of the vortex and it has been suggested that antiferromagnetism might develop
      there. Here we report the results of a high-field nuclear-magnetic-resonance
      (NMR) imaging experiment in which we spatially resolve the electronic structure
      of near-optimally doped YBa2Cu3O7-delta inside and outside vortex cores. Outside
      the cores, we find strong antiferromagnetic fluctuations, whereas inside we
      detect electronic states that are rather different from those found in
      conventional superconductors.

PMID- 11586355
TI  - Swollen liquid-crystalline lamellar phase based on extended solid-like sheets.
AB  - Ordering particles at the nanometre length scale is a challenging and active
      research area in materials science. Several approaches have so far been
      developed, ranging from the manipulation of individual particles to the
      exploitation of self-assembly in colloids. Nanometre-scale ordering is well known
      to appear spontaneously when anisotropic organic moieties form liquid-crystalline
      phases; this behaviour is also observed for anisotropic mineral nanoparticles
      resulting in the formation of nematic, smectic and hexagonal mesophases. Here we
      describe a lyotropic liquid-crystalline lamellar phase comprising an aqueous
      dispersion of planar solid-like sheets in which all the atoms involved in a layer
      are covalently bonded. The spacing of these phosphatoantimonate single layers can
      be increased 100-fold, resulting in one-dimensional structures whose periodicity
      can be tuned from 1.5 to 225 nanometres. These highly organized materials can be
      mechanically or magnetically aligned over large pH and temperature ranges, and
      this property can be used to measure residual dipolar couplings for the structure
      determination of biomolecules by liquid-state NMR. We also expect that our
      approach will result in the discovery of other classes of mineral lyotropic
      lamellar phases.

PMID- 11586356
TI  - High frequency of 'super-cyclones' along the Great Barrier Reef over the past
      5,000 years.
AB  - Understanding long-term variability in the occurrence of tropical cyclones that
      are of extreme intensity is important for determining their role in ecological
      disturbances, for predicting present and future community vulnerability and
      economic loss and for assessing whether changes in the variability of such
      cyclones are induced by climate change. Our ability to accurately make these
      assessments has been limited by the short (less than 100 years) instrumented
      record of cyclone intensity. Here we determine the intensity of prehistoric
      tropical cyclones over the past 5,000 years from ridges of detrital coral and
      shell deposited above highest tide and terraces that have been eroded into coarse
      grained alluvial fan deposits. These features occur along 1,500 km of the Great
      Barrier Reef and also the Gulf of Carpentaria, Australia. We infer that the
      deposits were formed by storms with recurrence intervals of two to three
      centuries, and we show that the cyclones responsible must have been of extreme
      intensity (central pressures less than 920 hPa). Our estimate of the frequency of
      such 'super-cyclones' is an order of magnitude higher than that previously
      estimated (which was once every several millennia), and is sufficiently high to
      suggest that the character of rainforests and coral reef communities were
      probably shaped by these events.

PMID- 11586357
TI  - Multiple benefits of gregariousness cover detectability costs in aposematic
      aggregations.
AB  - Understanding the early evolution of aposematic (warning) coloration has been a
      challenge for scientists, as a new conspicuous morph in a population of cryptic
      insects would have a high predation risk and would probably die out before local
      predators learnt to avoid it. Fisher presented the idea of aggregation benefit
      through the survival of related individuals; however, his theory has been
      strongly debated as the mechanisms that favour grouping have never been explored
      experimentally with the incorporation of detectability costs. Here we create a
      comprehensive 'novel world' experiment with the great tit (Parus major) as a
      predator to explore simultaneously the predation-related benefits and costs for
      aposematic aggregated prey, manipulating both group size and signal strength. Our
      results show that grouping would have been highly beneficial for the first
      aposematic prey individuals surrounded by naive predators, because (1)
      detectability risk increased only asymptotically with group size; (2) additional
      detectability costs due to conspicuous signals were marginal in groups; (3) even
      naive predators deserted the group after detecting unpalatability (dilution
      effect); and (4) avoidance learning of signal was faster in groups. None of these
      mechanisms require kin selection.

PMID- 11586358
TI  - Positive selection of a gene family during the emergence of humans and African
      apes.
AB  - Gene duplication followed by adaptive evolution is one of the primary forces for
      the emergence of new gene function. Here we describe the recent proliferation,
      transposition and selection of a 20-kilobase (kb) duplicated segment throughout
      15 Mb of the short arm of human chromosome 16. The dispersal of this segment was
      accompanied by considerable variation in chromosomal-map location and copy number
      among hominoid species. In humans, we identified a gene family (morpheus) within
      the duplicated segment. Comparison of putative protein-encoding exons revealed
      the most extreme case of positive selection among hominoids. The major episode of
      enhanced amino-acid replacement occurred after the separation of human and great
      ape lineages from the orangutan. Positive selection continued to alter amino-acid
      composition after the divergence of human and chimpanzee lineages. The rapidity
      and bias for amino-acid-altering nucleotide changes suggest adaptive evolution of
      the morpheus gene family during the emergence of humans and African apes.
      Moreover, some genes emerge and evolve very rapidly, generating copies that bear
      little similarity to their ancestral precursors. Consequently, a small fraction
      of human genes may not possess discernible orthologues within the genomes of
      model organisms.

PMID- 11586359
TI  - A forkhead-domain gene is mutated in a severe speech and language disorder.
AB  - Individuals affected with developmental disorders of speech and language have
      substantial difficulty acquiring expressive and/or receptive language in the
      absence of any profound sensory or neurological impairment and despite adequate
      intelligence and opportunity. Although studies of twins consistently indicate
      that a significant genetic component is involved, most families segregating
      speech and language deficits show complex patterns of inheritance, and a gene
      that predisposes individuals to such disorders has not been identified. We have
      studied a unique three-generation pedigree, KE, in which a severe speech and
      language disorder is transmitted as an autosomal-dominant monogenic trait. Our
      previous work mapped the locus responsible, SPCH1, to a 5.6-cM interval of region
      7q31 on chromosome 7 (ref. 5). We also identified an unrelated individual, CS, in
      whom speech and language impairment is associated with a chromosomal
      translocation involving the SPCH1 interval. Here we show that the gene FOXP2,
      which encodes a putative transcription factor containing a polyglutamine tract
      and a forkhead DNA-binding domain, is directly disrupted by the translocation
      breakpoint in CS. In addition, we identify a point mutation in affected members
      of the KE family that alters an invariant amino-acid residue in the forkhead
      domain. Our findings suggest that FOXP2 is involved in the developmental process
      that culminates in speech and language.

PMID- 11586360
TI  - Genome sequence of Yersinia pestis, the causative agent of plague.
AB  - The Gram-negative bacterium Yersinia pestis is the causative agent of the
      systemic invasive infectious disease classically referred to as plague, and has
      been responsible for three human pandemics: the Justinian plague (sixth to eighth
      centuries), the Black Death (fourteenth to nineteenth centuries) and modern
      plague (nineteenth century to the present day). The recent identification of
      strains resistant to multiple drugs and the potential use of Y. pestis as an
      agent of biological warfare mean that plague still poses a threat to human
      health. Here we report the complete genome sequence of Y. pestis strain CO92,
      consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2
      kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion
      sequences and displays anomalies in GC base-composition bias, indicating frequent
      intragenomic recombination. Many genes seem to have been acquired from other
      bacteria and viruses (including adhesins, secretion systems and insecticidal
      toxins). The genome contains around 150 pseudogenes, many of which are remnants
      of a redundant enteropathogenic lifestyle. The evidence of ongoing genome
      fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone
      large-scale genetic flux and provides a unique insight into the ways in which new
      and highly virulent pathogens evolve.

PMID- 11586361
TI  - An endogenous cannabinoid (2-AG) is neuroprotective after brain injury.
AB  - Traumatic brain injury triggers the accumulation of harmful mediators that may
      lead to secondary damage. Protective mechanisms to attenuate damage are also set
      in motion. 2-Arachidonoyl glycerol (2-AG) is an endogenous cannabinoid,
      identified both in the periphery and in the brain, but its physiological roles
      have been only partially clarified. Here we show that, after injury to the mouse
      brain, 2-AG may have a neuroprotective role in which the cannabinoid system is
      involved. After closed head injury (CHI) in mice, the level of endogenous 2-AG
      was significantly elevated. We administered synthetic 2-AG to mice after CHI and
      found significant reduction of brain oedema, better clinical recovery, reduced
      infarct volume and reduced hippocampal cell death compared with controls. When 2
      AG was administered together with additional inactive 2-acyl-glycerols that are
      normally present in the brain, functional recovery was significantly enhanced.
      The beneficial effect of 2-AG was dose-dependently attenuated by SR-141761A, an
      antagonist of the CB1 cannabinoid receptor.

PMID- 11586362
TI  - A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias
      of natural killer T cells.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a prototype autoimmune disease
      mediated by type 1 helper T (TH1) cells and under the control of regulatory
      cells. Here we report that a synthetic glycolipid ligand for CD1d-restricted
      natural killer T (NKT) cells expressing the semi-invariant T-cell receptor
      (Valpha14+) is preventive against EAE. The ligand is an analogue of alpha
      galactosylceramide (alpha-GC), a prototype NKT cell ligand, with a truncated
      sphingosine chain. alpha-GC causes NKT cells to produce both interferon (IFN)
      gamma and interleukin (IL)-4 (refs 4, 5). However, this new ligand can induce a
      predominant production of IL-4 by the NKT cells. A single injection of this
      glycolipid, but not of alpha-GC, consistently induced TH2 bias of autoimmune T
      cells by causing NKT cells to produce IL-4, leading to suppression of EAE. The
      lack of polymorphism of CD1d and cross-reactive response of mouse and human NKT
      cells to the same ligand indicates that targeting NKT cells with this ligand may
      be an attractive means for intervening in human autoimmune diseases such as
      multiple sclerosis.

PMID- 11586363
TI  - Direct ligand-receptor complex interaction controls Brassica self
      incompatibility.
AB  - Many higher plants have evolved self-incompatibility mechanisms to prevent self
      fertilization. In Brassica self-incompatibility, recognition between pollen and
      the stigma is controlled by the S locus, which contains three highly polymorphic
      genes: S-receptor kinase (SRK), S-locus protein 11 (SP11) (also called S-locus
      cysteine-rich protein; SCR) and S-locus glycoprotein (SLG). SRK encodes a
      membrane-spanning serine/threonine kinase that determines the S-haplotype
      specificity of the stigma, and SP11 encodes a small cysteine-rich protein that
      determines the S-haplotype specificity of pollen. SP11 is localized in the pollen
      coat. It is thought that, during self-pollination, SP11 is secreted from the
      pollen coat and interacts with its cognate SRK in the papilla cell of the stigma
      to elicit the self-incompatibility response. SLG is a secreted stigma protein
      that is highly homologous to the SRK extracellular domain. Although it is not
      required for S-haplotype specificity of the stigma, SLG enhances the self
      incompatibility response; however, how this is accomplished remains
      controversial. Here we show that a single form of SP11 of the S8 haplotype (S8
      SP11) stabilized with four intramolecular disulphide bonds specifically binds the
      stigma membrane of the S8 haplotype to induce autophosphorylation of SRK8, and
      that SRK8 and SLG8 together form a high-affinity receptor complex for S8-SP11 on
      the stigma membrane.

PMID- 11586364
TI  - Quality control of mRNA 3'-end processing is linked to the nuclear exosome.
AB  - An emerging theme in messenger RNA metabolism is the coupling of nuclear pre-mRNA
      processing events, which contributes to mRNA quality control. Most eukaryotic
      mRNAs acquire a poly(A) tail during 3'-end processing within the nucleus, and
      this is coupled to efficient export of mRNAs to the cytoplasm. In the yeast
      Saccharomyces cerevisiae, a common consequence of defective nuclear export of
      mRNA is the hyperadenylation of nascent transcripts, which are sequestered at or
      near their sites of transcription. This implies that polyadenylation and nuclear
      export are coupled in a step that involves the release of mRNA from transcription
      site foci. Here we demonstrate that transcripts which fail to acquire a poly(A)
      tail are also retained at or near transcription sites. Surprisingly, this
      retention mechanism requires the protein Rrp6p and the nuclear exosome, a large
      complex of exonucleolytic enzymes. In exosome mutants, hypo- as well as
      hyperadenylated mRNAs are released and translated. These observations suggest
      that the exosome contributes to a checkpoint that monitors proper 3'-end
      formation of mRNA.

PMID- 11586365
TI  - Transmission intensity and impact of control policies on the foot and mouth
      epidemic in Great Britain.
AB  - The foot and mouth disease (FMD) epidemic in British livestock remains an ongoing
      cause for concern, with new cases still arising in previously unaffected areas.
      Epidemiological analyses have been vital in delivering scientific advice to
      government on effective control measures. Using disease, culling and census data
      on all livestock farms in Great Britain, we analysed the risk factors determining
      the spatiotemporal evolution of the epidemic and of the impact of control
      policies on FMD incidence. Here we show that the species mix, animal numbers and
      the number of distinct land parcels in a farm are central to explaining regional
      variation in transmission intensity. We use the parameter estimates thus obtained
      in a dynamical model of disease spread to show that extended culling programmes
      were essential for controlling the epidemic to the extent achieved, but
      demonstrate that the epidemic could have been substantially reduced in scale had
      the most efficient control measures been rigorously applied earlier.

PMID- 11586370
TI  - The Optimal Drug Therapy National Symposium 2001: a call for action.
AB  - There is widespread concern internationally and within Canada about the rapid
      escalation in pharmaceutical costs. Although there is reason to believe that the
      quality of prescribing has improved in recent years, with heightened emphasis on
      evidence-based therapeutic decision-making, there is enormous pressure to
      prescribe in almost every clinical situation. Busy clinicians need improved tools
      to aid therapeutic decision-making. Access to timely information about drug
      efficacy and safety is essential. Most importantly, there is a need for a new
      partnership model that may blend the interests of patients, professionals, payors
      and manufacturers to better define disease state management approaches that will
      lead to an optimal return on the investment in pharmaceutical care. The new model
      will depend on high standards of research to show what does and does not work to
      secure the most effective pharmacotherapy. It will also require renewed efforts
      in education for patients and caregivers, and progress on that front will, in
      turn, rely on the most effective use of expanded capacity in information
      technology. One early impact will be seen in the reduction of medication errors.
      The framework for therapeutic decision-making must evolve in keeping with the
      revolution in human biology. With improved understanding of human genomics and
      proteomics, prescribers are better able to consider highly individualized and
      targeted drug therapies while actively concentrating on risk minimization. The
      Optimal Drug Therapy National Symposium 2001 has created a consensus among
      stakeholders and pointed the way to improvements in drug therapy that may be
      achieved through enhanced research, educa- tion, public involvement and
      professional support. Unequivocal commitment to the laudable goal of optimal drug
      therapy is now required from all sides.

PMID- 11586371
TI  - The future of evidence-based medicine.
AB  - Evidence-based medicine (EBM) stresses the examination of evidence from clinical
      research as an important basis for the practice of medicine. EBM is an approach
      that is intuitively reasonable, and is increasingly taught in medical schools and
      incorporated into practice. Although it is often not feasible for busy clinicians
      to find and appraise original research themselves, EBM is now frequently used to
      develop clinical practice guidelines. However, there are often 'grey areas' in
      the interpretation of the evidence, some of which are discussed in this paper.
      Clinical medicine can be complex, and EBM will never provide easy answers to
      difficult problems, which means that there will always be an art to clinical
      medicine. As well, EBM is practised in complex, semirational, constantly changing
      health care systems, which sometimes actually establish barriers to the
      incorporation of evidence into practice.

PMID- 11586372
TI  - The challenge with tracking health outcomes.
AB  - Rising health care costs, questions about the effectiveness of medical
      interventions and demands for greater accountability and efficiency with respect
      to health care delivery have led to a growing interest in using patient outcomes
      as a primary measure of the quality of care. However, measuring outcomes is
      complex and expensive given the widespread lack of an integrated and
      comprehensive electronic health information system. Furthermore, the science of
      outcome measurement is relatively undeveloped and caution needs to be taken when
      attempting to relate health care provision to differences in outcomes. While the
      foregoing problems do not invalidate outcome measurement programs, they do stress
      the point that such initiatives need to be pursued cautiously and that their
      limitations must be clearly appreciated. The challenge with tracking health
      outcomes is discussed from the perspective of the Improving Cardiovascular
      Outcomes in Nova Scotia study. This outcome measurement and management project,
      one of the most ambitious ever undertaken in Canada, has been seeking to improve
      the medical care of patients with cardiovascular disease in Nova Scotia since
      October 1997.

PMID- 11586373
TI  - The science of health technology assessment--the economic perspective.
AB  - Economic evaluation is a component of health technology assessment. Methods for
      economic evaluation began to be developed about 30 years ago. More recently,
      governments have encouraged the development of methodological and reporting
      guidelines for economic evaluation in health care with the major focus being
      placed on pharmaceutical products. There are two aspects of economic evaluations
      discussed in the present paper: the science of the techniques used and the
      utility of the resulting evaluations. Although activity is increasing in this
      area, it is still not clear how useful such 'value for money' evaluations have
      actually been and how much they have been used. It seems that the 'value for
      money' of 'value for money' evaluations of pharmaceutical products has yet to be
      shown.

PMID- 11586374
TI  - The science of health technology assessment--clinical effectiveness of
      therapeutic interventions.
AB  - Important information is not, and cannot, be available at the time a new drug
      enters the market. Delaying registration is not the answer because most of this
      information can only be obtained in a real life situation. Several types of
      postmarketing (phase IV studies) can be identified. The active pharmacovigilance
      cohort who allows large number of patients to be followed for long periods of
      time can answer questions about the incidence of rare events (less than one of
      3000 patients). The prospective effectiveness cohort can answer questions on long
      term efficacy (more than two years). The simplified clinical trial, which implies
      randomly assigning patients and then following them with a 'naturalistic'
      protocol can answer questions about effectiveness (efficacy in real life). The
      drug use study is the only way to answer questions of key importance to drug plan
      managers such as 'which drug(s) is it going to replace?' and 'is it going to be
      used as first line or second line?'. Phase IV studies, which in some cases should
      be mandatory (conditional registration), are essential for the protection of the
      patients and the proper use of public funds to reimburse drugs.

PMID- 11586375
TI  - The science of health technology assessment: the safety perspective.
AB  - Efforts to enhance the reporting and analysis of drug reactions have increased
      over recent years. Research into the pathogenesis, diagnosis and epidemiology has
      yielded important insights, yet major gaps in our management of drug safety still
      exist. Drug-induced diseases are an important cause of morbidity and mortality.
      Current ad hoc reporting systems fail to collect more than 10% of even the most
      serious of reactions. Drug reaction syndromes lack universally accepted
      definitions and names. Effective therapies for drug-induced diseases are few and
      poorly studied. Information about how to diagnose and treat drug-induced diseases
      is not reaching practitioners. Stakeholders, including regulatory agencies,
      funding agencies, the pharmaceutical industry, physicians, pharmacists and
      patient advocacy groups, need to work together to improve the systematic approach
      to drug safety and to make all stakeholders aware of advances in the technology
      surrounding drug-induced disease. The technology is available to make major
      strides in improving the overall management of drug-induced disease. The major
      barrier to progress is the lack of leadership from any of the powerful sectors
      involved in drug use.

PMID- 11586376
TI  - The place for prescribing guidelines and the means of their dissemination.
AB  - Practice guidelines are of potential benefit when a physician recognizes that
      they do not have all the facts required for providing appropriate health care.
      However, when guidelines for prescribing are known to the prescriber, and the
      physician chooses to modify or ignore them, their behaviour is being driven by
      personal and professional value systems that are in conflict with their knowledge
      base. Thus, providing practice guidelines to these physicians will not reduce
      suboptimal prescribing practices. In these circumstances, a number of studies
      suggest that addressing the social and situational involvement of physicians
      within the guidelines may enhance the promulgation and implementation of
      guidelines, and lead to more optimal prescribing choices for physicians.

PMID- 11586377
TI  - The place of guidelines and their means of dissemination.
AB  - INTRODUCTION: The literature shows that physicians do not change their patterns
      of practice quickly. With thousands of conflicting guidelines available, many
      disseminated by print, there has been little measurable impact of new guidelines
      on physician prescribing patterns. METHODS: A series of interventions designed to
      improve physician uptake of guidelines is described. Interventions evaluated in a
      series of trials include mail dissemination, small group continuing medical
      education sessions, academic detailing by both academic detailers and
      pharmaceutical detailers, and a whole community program known as the Program for
      Appropriate Anti-Infective Community Therapy. RESULTS: Only the whole community
      intervention had significant impact on physician prescribing patterns. The
      changes involved a significant reduction in anti-infective use and a significant
      change from the use of second- and third-line drugs to first-line drugs, as
      specified in the Ontario Anti-Infective Guidelines. CONCLUSIONS: Acceptable
      guidelines disseminated by a multidisciplinary community program can have a
      positive impact on physician prescribing patterns. To increase the acceptability
      of guidelines for whole community dissemination, a new innovation (Guideline
      Advisory Committee) that scores the quality of guidelines and selects the most
      objectively produced guideline is described.

PMID- 11586378
TI  - The impact of pharmacotherapy policy: a case study.
AB  - Universal drug insurance coverage has been endorsed by the National Health Forum
      and the Liberal government as a means of providing equitable access to
      prescription medication for Canadians. In 1996, Quebec legislated a universal
      drug insurance program. To finance extended coverage for approximately 1.2
      million previously uninsured beneficiaries, an income-indexed coinsurance and
      deductible cost-sharing policy was introduced for previously insured
      beneficiaries (people 65 years of age and older, and those receiving income
      security allowance). The increase in cost-sharing for previously insured
      beneficiaries led to a reduction in both essential (senior citizens: 9.1%; income
      security: 14.4%) and less essential medication (senior citizens: 15.1%; income
      security: 22.4%). Reductions in the use of essential drugs were associated with
      an increase in the rate of emergency visits (by 43% in senior citizens and 78% in
      income security recipients) and adverse events (by over 100% in senior citizens
      and 88% in income security recipients). The 442 physicians and pharmacists who
      were surveyed reported that the policy reduced the use of antilipidemics, inhaled
      steroids and antihypertensives in the previously insured beneficiaries, but
      improved access to previously unaffordable medications for cardiac disease and
      asthma in the newly insured beneficiaries. Although universal drug insurance
      appeared to enhance access to essential medication for the newly insured, these
      benefits were exacted at a cost of producing unintended health effects in two
      vulnerable subgroups: senior citizens and income security recipients. Because no
      prior studies have shown that consumer cost sharing can lead to expected
      objective of selective reductions in less essential drug use alone, alternate
      policy approaches for financing universal drug coverage need to be considered.

PMID- 11586379
TI  - Reinventing the government role in pharmacotherapy.
AB  - Governments face enormous challenges in managing escalating expenditures under
      their prescription drug plans while providing access to new, cost effective
      therapies. Strategies to address cost pressures must be considered carefully,
      however, to ensure the achievement of optimum health outcomes. Alberta has
      adopted an inclusive approach in addressing utilization and cost issues through a
      variety of advisory processes and initiatives supported by the Minister of Health
      and Wellness. The Expert Committee on Drug Evaluation and Therapeutics advises
      the Minister on Alberta's government-sponsored drug programs and related policy
      matters. The Alberta Management Committee on Drug Utilization, co-chaired by the
      Alberta Medical Association and the Pharmacists Association of Alberta, is
      mandated to oversee the implementation of a number of drug utilization
      initiatives. The Pharmaceutical Information Network is the cornerstone project of
      Alberta Wellnet, supported by a unique multistakeholder task force that includes
      physicians, pharmacists, representatives from health regions and government.
      Recent successful program launches in Alberta include a palliative drug program,
      trial prescription program and the multiple sclerosis drug program. Successes in
      Alberta reinforce the importance of government's role in achieving optimum
      pharmacotherapy. This role can only be undertaken in collaboration with key
      stakeholders.

PMID- 11586380
TI  - Pharmaceutical industry overview: optimal drug therapy.
AB  - Today's revolutionary genomics research is the key to the search for tomorrow's
      new drugs. Over the next 10 to 20 years, there could be 15 times the number of
      therapeutic agents that there are today. With these scientific advances, optimal
      drug therapy becomes an even more significant component of health care. Canada's
      Research-Based Pharmaceutical Companies have proposed a therapeutic management
      system designed to make the optimum use of health care while controlling costs.
      The proposal is based on the disease management approach, applied first to
      diseases that are the most widespread in the population and that represent the
      highest costs for the health care system. The concept involves comparing the best
      available practices with the care provided and making the necessary adjustments
      to improve patients' health in line with the most cost effective approach.
      Preliminary results from similar programs underway in Canada, such as those in
      the field of asthma treatment, suggest that they can lead to improvements in the
      quality of care and represent a step forward in comparison with measures focusing
      only on cutting costs. The future will bring new challenges in achieving optimal
      drug therapy as genomics leads to tailor-made medications, necessitating changes
      in drug plan policies and reimbursement. With personalized treatment regimens and
      an increased understanding of how to prevent and treat diseases, optimal drug
      therapy can be taken to a new level. Quality of life can be further improved,
      more lives can be saved and the health care system can be saved more money while
      providing the best possible treatments.

PMID- 11586381
TI  - Optimal drug therapy: the role of the pharmacist in bridging the gap between
      knowledge and action.
AB  - Drug expenditures are rising more rapidly than other health care spending. There
      are a number of reasons for this difference, including the volume of medications
      available. Optimal drug therapy is the goal for every patient. Physicians and
      nurses are experiencing difficulty coping with increased health care needs and
      have not been able to control drug expenditures. Pharmacists, who are trained to
      deliver pharmaceutical care, should be an integral part of the system. Improved
      partnerships among patients, physicians and pharmacists have shown conclusively
      that the pharmacist has an important role in the delivery of health care cost
      effectiveness. Together, using their respective knowledge base, pharmacists and
      physicians could provide optimal drug therapy, which would be of benefit to
      patients and the health care system. This might involve a change in the
      reimbursement system for pharmacists.

PMID- 11586382
TI  - Optimal Drug Therapy National Symposium 2001: reflections and conclusions.

PMID- 11586385
TI  - All the world's a clinical trial.

PMID- 11586386
TI  - CCS Consensus Conference 2001 update: recommendations for the management of
      adults with congenital heart disease. Part I.

PMID- 11586387
TI  - Perfusion of isolated organs and the first heart-lung machine.
AB  - In 1885, Max von Frey (1852-1932), while working in Carl Ludwig's Physiological
      Institute in Leipzig, Germany, designed an apparatus that had criteria
      characteristic of a heart-lung machine. With this device, he perfused the entire
      lower extremity of dogs, and took measurements of oxygen consumption, and carbon
      dioxide and lactate production. In 1935, another type of perfusion apparatus was
      constructed by Charles A Lindbergh (1902-1973). This device was the result of
      cooperation with Alexis Carrel (1873-1944) who was a pioneer of experimental
      organ transplantation. Using Lindbergh's pulsating device, organs such as
      thyroid, ovary, suprarenal gland, spleen, heart and kidney from fowls and cats
      were perfused with an oxygenated medium, and were maintained under sterile
      conditions. Beginning in 1934, John H Gibbon (1903-1973) developed and tested a
      heart-lung machine to institute cardiopulmonary bypass in cats during
      experimental occlusion of the pulmonary artery. In 1953, he performed the first
      successful open-heart operation in a patient using a heart-lung machine. This
      included elements that were similar to those used by von Frey - ie, the
      oxygenator and the pumps for continuous circulation of blood. A comparison of the
      three experimental devices revealed the following: the application for
      experimental purposes preceded clinical use; the development shifted from Europe
      to the United States, and was achieved by people who were not specialists; and
      the intention to build such a device was first purely scientific interest, but
      later shifted to the care for and treatment of patients with heart and
      circulatory defects by open-heart surgery.

PMID- 11586388
TI  - Acute pericarditis with transient constriction.
AB  - Transient constrictive pericarditis is a rare entity. It is characterized by
      clinical and echocardiographic features similar to constrictive pericarditis, but
      is distinguished by its transient nature. This feature is important to recognize
      for avoiding unnecessary pericardectomy. The case of a patient who presented with
      acute myopericarditis and typical echocardiographic features of constriction is
      described. Within weeks, all signs of constriction disappeared spontaneously.

PMID- 11586389
TI  - Mass confusion.
AB  - A patient is reported who presented to the hospital with a benign arrhythmia and
      what was initially believed to be a benign intracardiac tumour as imaged by
      transthoracic echocardiography and a first transesophageal echocardiogram.
      Comprehensive assessment with a second transesophageal echocardiogram revealed
      extensive extra- and intracardiac involvement by masses with many malignant
      appearing features, including compression of vascular structures in the
      mediastinum. Peripheral biopsy yielded a diagnosis of high-grade lymphoma. The
      clinical, echocardiographic and radiological findings are discussed, as are the
      expected features of myxomae, and by comparison, common features of malignancy.
      The ability of transesophageal echocardiography, when comprehensively performed,
      to define the location and extent of mass lesions, and their physiological
      impact, such as compression of the pulmonary vasculature, by two-dimensional
      imaging and spectral Doppler are emphasized.

PMID- 11586390
TI  - Acute bacterial endocarditis on myxomatous mitral valve.

PMID- 11586391
TI  - Reflections from the seashore.

PMID- 11586392
TI  - Effect of exogenous nitric oxide on electrogenesis in myelinated and unmyelinated
      nerve fibers.
AB  - Extracellular recording was used to study the effect of sodium nitroprusside, a
      donor of NO, on parameters of action potential and ionic currents in single
      sciatic nerve fibers and unmyelinated nerve terminals in the sternal muscle in
      frogs. Sodium nitroprusside significantly decreased the duration of action
      potential in Ranvier node and the amplitude of afterdepolarization. In motor
      nerve terminals bathed in low Ca(2+) saline, sodium nitroprusside increased phase
      III amplitude of the nerve terminal response corresponding to outward potassium
      currents. Blockade of voltage-dependent potassium channels with 4-aminopyridine
      abolished the effects of NO. These data indicate that exogenous NO reduced the
      duration of action potential and afterdepolarization through enhancement of
      voltage-dependent potassium currents.

PMID- 11586393
TI  - Effect of prenatal stress on tonic pain in rats.
AB  - The effect of prenatal stress on specific biphasic behavioral response in 25-day
      rat pups was studied using the experimental model of formalin-induced tonic pain.
      Prenatally stressed rats showed hypersensitivity to tonic nociceptive stimulation
      manifested in increased amplitude and duration of the response. Behavioral
      responses observed during the interphase period attest to impairment of
      inhibitory processes (more pronounced in females). These findings suggest that
      the interphase interval is the period of active inhibitory process rather than
      rest period.

PMID- 11586394
TI  - A new insight into mechanisms of age-related changes in heart rate.
AB  - Changes in cardiac rhythm induced by blockade of hyperpolarization currents with
      ZD 7288 depend on animal's age. The increase in cardiointerval duration is
      related to prolongation of T-P segment on ECG. It is hypothesized that the age
      related changes in activity of hyperpolarization channels are determined by a
      modulating effect of the autonomic nervous system.

PMID- 11586395
TI  - Activation of type II cannabinoid receptors improves myocardial tolerance to
      arrhythmogenic effects of coronary occlusion and reperfusion.
AB  - Preliminary intravenous injection of cannabinoid receptor agonist HU-210 (0.05
      mg/kg) reduced the incidence of ventricular arrhythmias during 10-min coronary
      occlusion and 10-min reperfusion in chloralose-anesthetized rats. Preliminary
      injection of type I cannabinoid receptor antagonist SR 141716A (3 mg/kg) had no
      effect on the antiarrhythmic effect of HU-210, while type II cannabinoid receptor
      antagonist SR 144528 (1 mg/kg) completely abolished the effect of HU-210.
      Preconditioning with glibenclamide (0.3 mg/kg), an inhibitor of ATP-dependent
      K(+)-channels, did not affect the antiarrhythmic activity of HU-210. These
      findings suggest that antiarrhythmic effect of HU-210 is mediated through
      activation of type II cannabinoid receptors rather than activation of K(+)
      channels.

PMID- 11586396
TI  - DTNB inhibits calcium response of rat brain cortical slices to anoxia of various
      duration.
AB  - The effects of DTNB on changes in intracellular Ca(2+) content in slices of rat
      cortex induced by 2- or 10-min anoxia were studied fluorometrically. DTNB (200
      microM) prevented excessive intracellular Ca(2+) accumulation during and after 10
      min anoxia and moderate increase in Ca(2+) content induced by 2-min anoxia. Our
      results suggest that redox sites of NMDA receptors participates in both
      pathogenic and adaptive Ca(2+)-mediated processes activated by anoxia.

PMID- 11586397
TI  - Genetically determined differences in the resistance to myocardial infarction in
      Wistar and August rats.
AB  - In intact August rats, the cardiac contractile function at rest was by 76% higher
      than in Wistar rats, while their hearts, both intact and after acute myocardial
      infarction, were more resistant to isometric load than the hearts of Wistar rats.
      Postinfarction mortality in August rats was 18% vs. 70% in Wistar rats.
      Adrenoreactivity of the myocardium in August rats was decreased compared to that
      in Wistar rats. These peculiarities can determine high resistance of August rats
      to myocardial infarction.

PMID- 11586398
TI  - Formation of hydroxyl radicals during myocardial reperfusion after experimental
      ischemia of different duration.
AB  - The intensity of hydroxyl radical (OH*) formation in the myocardium during
      reperfusion after ischemia of different duration was evaluated using
      microdialysis with sodium salicylate. 2,3-Dihydroxybenzoic acid, a product of OH*
      trapping by salicylic acid, was used as a marker of OH* generation in the
      postischemic myocardium. Experiments were performed on open-chest anesthetized
      and jet-ventilated Wistar rats. The concentrations of 2,3-dihydroxybenzoic acid
      in the dialysate were measured by high performance liquid chromatography (HPLC)
      with electrochemical detection. Experiments showed that the intensity and
      duration of free oxygen radical generation during reperfusion after 30-min
      ischemia far surpassed those observed after 20-min ischemia.

PMID- 11586399
TI  - Possible correction of lymph flow and contractile activity of lymphatic
      microvessels during febrile response.
AB  - In experiments on dogs and rats dimephosphon considerably enhanced contractile
      activity of walls and valves in lymphatic microvessels, thus accelerating lymph
      flow and improving exchange between blood and lymph.

PMID- 11586400
TI  - Free radical oxidation and antioxidant activity in blood plasma and myocardium
      during long-term dipyridamole treatment.
AB  - Activation of free radical oxidation and inhibition of antioxidant activity in
      mouse myocardium after long-term dipyridamole treatment were demonstrated using
      chemiluminescent techniques. At the same time, dipyridamole 10-fold inhibited
      free radical oxidation and slightly increased antioxidant activity in the plasma.
      Dipyridamole-induced platelet disaggregation was accompanied by an increase in
      platelet count.

PMID- 11586401
TI  - Effects of 1,2,3,4-tetrahydroimidazo[4,5-c]-pyridine derivatives on ethanol
      oxidation by alcohol dehydrogenase isoforms from human liver.
AB  - We studied in vitro effects of four 1,2,3,4-tetrahydroimidazo[4,5-c]-pyridine
      derivatives formed in the reaction of the corresponding aldehydes with histidine
      on the rate of ethanol oxidation by alcohol dehydrogenase isoforms from human
      liver. None of test compounds inhibited ethanol oxidation by these enzymes. Some
      of them increased alcohol dehydrogenase activity to 220-240% of the initial
      level. Only one test compound accelerated ethanol oxidation by b1b2-alcohol
      dehydrogenase (150% of the control). The molecular mechanism underlying these
      effects of 1,2,3,4-tetrahydroimidazo[4,5-c]-pyridine derivatives on ethanol
      oxidation by alcohol dehydrogenase isoforms from human liver is discussed.

PMID- 11586402
TI  - Effect of nutritional indoles on activity of xenobiotic metabolism enzymes and T
      2 toxicity in rats.
AB  - Experiments on Wistar rats showed that feeding a ration containing 0.1%
      concentrate of food indoles (indole-3-carbinole and ascorbigen) for 3 weeks
      increased activity of phases I and II xenobiotic metabolism enzymes in the liver
      and intestinal mucosa and weakened the toxic effects of trichothecene T-2
      mycotoxin. Activity of the key enzymes of T-2 detoxification, microsomal
      carboxylesterase and UDP-glucuronosyl transferase, was 1.5-2-fold higher in rats
      receiving T-2 toxin against the background of indole-enriched diet compared to
      toxin-treated rats kept on standard ration.

PMID- 11586403
TI  - Immunological memory in CBA and CBA/N mice after vaccination with Mycobacterium
      bovis (BCG).
AB  - In inbred CBA and CBA/N mice immunological memory was induced by subcutaneous
      injection of Mycobacterium bovis (BCG). Experiments with adoptive transfer of
      spleen T cells and ionomycin-resistant T cells (memory cells) between CBA and
      CBA/N mice in various combinations showed that immunological memory was not
      formed in CBA/N mice, but can be induced by adoptive transfer of cells from CBA
      mice.

PMID- 11586404
TI  - Immunoenzyme assay of glial fibrillary acidic protein for evaluation of
      functional activity of cell grafts from embryonic ventral mesencephalon in rats
      with experimental hemiparkinsonism.
AB  - The relationship between the release of glial fibrillary acidic protein (GFAP)
      into systemic circulation and the efficacy of transplantation of embryonic
      nervous tissue was studied on rats with 6-OHDA-induced hemiparkinsonism. It was
      found that intrastriatal transplantation of cell preparations from embryonic
      ventral mesencephalon significantly attenuated apomorphine-induced rotation,
      which points to functional recovery of the dopaminergic nigrostriatal system. The
      degree of this recovery depends on reactive astrogliosis around the graft and
      survival of dopaminergic neurons. Analysis of GFAP concentration revealed
      significant elimination of this antigen into the circulation 7 and 14 days after
      transplantation. In rats with good consolidation of the graft without pronounced
      reactive gliosis, the concentration of GFAP reached 253.99+/-79.30 ng/ml on week
      4 after transplantation and decreased to 8.2+/-3.3 ng/ml 8-12 weeks after
      transplantation. In rats with poor graft consolidation associated with death of
      transplanted neurons and gliosis in the graft and surrounding tissue the
      concentration GFAP increased to 476.4+/-111.0 ng/ml within 4 weeks after
      transplantation and remained elevated (235.0+/-44.8 ng/ml) for 12 weeks. Thus,
      monitoring of serum GFAP concentrations allows in vivo evaluation of the
      functional state of intracerebral graft and the level of reactive gliosis. This
      test can be used for the prognosis of transplantation efficacy.

PMID- 11586405
TI  - Free radical generation in ejaculate samples from infertile patients.
AB  - Generation of free radicals in ejaculate samples from infertile patients was
      evaluated using chemiluminescent technique. The presence of antisperm antibodies
      in samples increased the possibility of damages to spermatozoon plasma membranes
      due to excessive generation of free radicals.

PMID- 11586406
TI  - Inhibitory effect of peptide vilon on the development of induced rat urinary
      bladder tumors in rats.
AB  - The effect of peptide vilon (Lys-Glu) on urinary bladder carcinogenesis in rats
      was studied. Urinary bladder tumors were induced with a selective carcinogen N
      butyl-N-(4-hydroxybutyl)nitrosamine. The tumors developed in 56% vilon-treated
      animals and in 75.5% controls. Vilon 2-fold decreased the incidence of
      preneoplastic and early neoplastic changes in urinary bladder mucosa and
      significantly inhibited carcinogenesis.

PMID- 11586407
TI  - Antigenic structure of ovarian cancer metastases.
AB  - Twenty highly specific (organ-specific and tumor-associated) antigens named
      ovarian metastatic antigens were revealed using polyclonal antibodies isolated
      from rabbits after immunization with soluble antigens from ovarian cancer
      metastases. These protein antigens were not detected by precipitating test system
      (sensitivity 1 mg/liter) in tissues of adult humans (except for organ-specific
      antigens) and blood plasma from healthy donors. Ovarian metastatic antigens
      included organ-specific, placenta-specific, tumor embryonic, tumor-associated,
      and reactive proteins. The precipitating test system identified 15 antigens in
      the amniotic fluid from pregnant women and 7 antigens in the plasma from patients
      with ovarian cancer (incidence 16-75%).

PMID- 11586408
TI  - Compensatory reactions during impairment of granulocytic stem in patients with
      lung cancer receiving antitumor chemotherapy.
AB  - We compared changes in the granulocytic hemopoietic stem in patients with stage
      III-IV lung cancer receiving cytostatic therapy by the original CVC and standard
      CAM schemes. In patients treated with the CVC regimen, the granulocytic
      hemopoietic stem possessed more potent compensatory capacities.

PMID- 11586409
TI  - Early effects of cis-dichlorodiammine platinum (II) on tumor progression and
      programmed death of Ehrlich ascites carcinoma cells.
AB  - We studied the effects of cis-dichlorodiammine platinum (II) on different
      pathways of cell death in cultured Ehrlich ascites carcinoma in vitro and on
      subsequent growth of transplanted tumor in vivo. One-hour incubation with the
      cytostatic modulated apoptosis in cell culture. However, exposure of cell culture
      to a minimal effective concentration of cis-platinum(II)diammine dichloride
      promoted the growth of transplanted tumor.

PMID- 11586410
TI  - Effect of irradiation on colony-forming ability of stem cells from patients with
      ovarian cancer.
AB  - In patients with ovarian cancer, the colony-forming capacity and radiosensitivity
      of clonogenic tumor cells from the primary node and metastases (ascites) differed
      considerably.

PMID- 11586411
TI  - Cell culture test system for express analysis of cytotoxic and growth-stimulating
      effects of bioactive compounds.
AB  - Cultures of human and mammalian cells presenting 4 types of differentiation
      (normal human fibroblasts and myoblasts, human and Syrian hamster hepatoma cells,
      and mouse/mouse hybridoma cells) were used in a panel biotest system. This system
      allowed to evaluate the cytotoxic and stimulatory effect of bioactive compounds
      by determining the dose-effect relationships and some quantitative parameters
      including LD(50). Examination of some biolactive compounds of different nature
      (sangviritrin, escin, deltostim, cycloheximide, dexamethasone) confirmed high
      efficacy of this biotest system.

PMID- 11586412
TI  - Apoptosis in woman uterine cervix in pathologies associated with human
      papillomavirus.
AB  - The level of apoptosis in uterine cervical tissue was evaluated in healthy women
      and in patients with various pathologies. No signs of apoptosis were found in
      unchanged stratified epithelium, condyloma latum, and condyloma acuminatum. The
      level of apoptosis decreased with progression of neoplastic epithelial
      transformations, usually no apoptosis was observed in samples of stage III
      cervical intraepithelial neoplasms. The development of preinvasive carcinoma was
      accompanied by activation of apoptotic processes most pronounced in the upper
      third of the epithelium. In some stage I and stage I-II cervical intraepithelial
      neoplasms, apoptosis and elimination of the basal layer cells caused rejection of
      the epithelium which can explain regression of this pathology at the initial
      stages. The prevalence of human papillomavirus infection directly correlated with
      neoplastic changes in the cervical epithelium.

PMID- 11586413
TI  - Effect of the dipeptide vilon on activity of digestive enzyme in rats of various
      ages.
AB  - Peroral administration of Vilon (Lys-Glu) to male and female Wistar rats aging 3
      and 11 months changed activity of digestive enzymes (invertase, maltase, alkaline
      phosphatase, and amino- and dipeptidases) in various portions of the
      gastrointestinal tract. The increase in enzyme activity was most pronounced in 11
      month-old animals, which diminished differences between rats of various ages. Our
      results indicate that Vilon produces positive effects on digestive enzyme
      activity during aging.

PMID- 11586414
TI  - Monoamine oxidase activity, lipid peroxidation, and morphological changes in
      human hypothalamus during aging.
AB  - Progressive gliosis of the hypothalamus during aging in humans is accompanied by
      activation of monoamine oxidase B activity, intensification of lipid
      peroxidation, and inhibition of SDH. Density of capillaries decreases. The role
      of monoamine oxidase B in the induction of lipid peroxidation is discussed.

PMID- 11586415
TI  - Alterative and plastic insufficiency of cardiomyocytes: isoproterenol-induced
      damage to myocardium during anthracycline cardiomyopathy.
AB  - The development of regenerative and plastic myocardial insufficiency induced by
      anthracycline antibiotic rubomycin is accompanied by a decrease in cardiomyocyte
      sensitivity to damage produced by synthetic catecholamine isoproterenol. The
      incidence and the size of coagulation necrosis foci of cardiomyocytes developed 6
      h after isoproterenol injection significantly decreased with increasing in the
      interval between rubomycin injection and subsequent administration of
      isoproterenol. In Wistar rats receiving rubomycin 3-5 days prior to isoproterenol
      and exhibiting signs of regenerative and plastic insufficiency, no cardiomyocyte
      contracture, intracellular myocytolysis, or lump degradation characteristic of
      cardiac insufficiency induced by endo- and exogenous catecholamines were found.

PMID- 11586416
TI  - Pathomorphological and biosynthetic changes in gastric epithelium during chronic
      duodenal ulcer.
AB  - We studied structural changes and biosynthetic processes in the gastric
      epithelium in patients with chronic duodenal ulcer. The severity of alterative
      ultrastructural changes in surface epithelial and glandular cells progressively
      increased from proximal to distal portion of the stomach. Biosynthesis of nucleic
      acids within the epithelium depended on the morphofunctional state of
      epitheliocytes. DNA biosynthesis in the fundus was less intensive. The intensity
      of RNA synthesis did not differ between various gastric regions. Our results
      suggest that structural and metabolic dimorphism of the fundic and pyloric
      epithelium underlies pathological changes in the mucosa during ulcer disease.

PMID- 11586417
TI  - Serotonin-producing cells in duodenum of Siberian chipmunk under various seasonal
      conditions.
AB  - We studied species-specific characteristics of enterochromaffin cells in the
      duodenum in Siberian chipmunk in various physiological states. Predominance of
      synthetic or secretory phase in enterochromaffin cell activity depends on body
      temperature, metabolism, and feeding behavior.

PMID- 11586418
TI  - Structure of renal glomeruli in hypertensive NISAG rats reared by normotensive
      females.
AB  - Morphometry of ultrastructural components of renal glomeruli in 3-week- and 6
      month-old rats with hereditary stress-induced arterial hypertension (NISAG rats)
      reared by normotensive Wistar females showed deceleration of the development of
      arterial hypertension in NISAG rats and attenuated its negative consequences for
      kidneys as the target organs.

PMID- 11586419
TI  - New experimental model of multiple myeloma.
AB  - NSO/1 (P3x63Ay 8Ut) and SP20 myeloma cells were inoculated to BALB/c OlaHsd mice.
      NSO/1 cells allowed adequate stage-by-stage monitoring of tumor development. The
      adequacy of this model was confirmed in experiments with conventional
      cytostatics: prospidium and cytarabine caused necrosis of tumor cells and reduced
      animal mortality.

PMID- 11586421
TI  - The schistosome vectors in the Americas.

PMID- 11586422
TI  - Schistosomiasis epidemiology and control: how did we get here and where should we
      go?
AB  - Although a disease of great antiquity, scientific studies of schistosomiasis
      began only 150 years ago. The complete life-cycle was not described until just
      before the First World War, making it possible at last to plan proper community
      control programmes. Inadequate tools prevented their effective implementation
      until well after the Second World War when new tools became available, thanks to
      the newly formed World Health Organization. Molluscicides spearheaded control
      programmes until the late 1970s but were then replaced by the newly developed,
      safe drugs still used today. Whatever the method used, the initial goal of
      eradication was, in the light of experience and cost, gradually replaced by less
      ambitious targets; first to stop transmission and then to reduce morbidity. The
      most successful programmes combined several methods to minimise reinfection after
      chemotherapy. Comparisons between different programmes are difficult without
      using appropriate, standardised diagnostic techniques and the correct
      epidemiological measurements. Some examples will be presented, mainly from our
      studies on Schistosoma mansoni in Kenya. Drug resistance on a scale comparable
      with malaria has not occurred in schistosomiasis but the likely withdrawal of all
      drugs except praziquantel leaves its control extremely vulnerable to this
      potential problem. An effective, affordable vaccine for use in endemic countries
      is unlikely to be ready for at least 5 years, and developing strategies for its
      use could take a further decade or more, judging from experience with drugs and
      molluscicides. In the interim, by analogy with malaria, the most cost-effective
      approach would the use of drugs combined with other methods to stop transmission,
      including molluscicides. The cost of molluscicides needs to be reduced and fears
      allayed about their supposedly adverse ecological effects.

PMID- 11586423
TI  - The identification and characterization of new immunogenic egg components:
      implications for evaluation and control of the immunopathogenic T cell response
      in schistosomiasis.
AB  - In schistosomiasis, granuloma formation to parasite eggs signals the beginning of
      a chronic and potentially life-threatening disease. Granulomas are strictly
      mediated by CD4+ T helper (Th) cells specific for egg antigens; however, the
      number and identity of these T cell-sensitizing molecules are largely unknown. We
      have used monoclonal T cell reagents derived from egg-sensitized individuals as
      probes to track down, isolate and positively identify several egg antigens; this
      approach implicitly assures that the molecules of interest are T cell immunogens
      and, hence, potentially pathogenic. The best studied and most abundant egg
      component is the Sm-p40 antigen. Sm-p40 and its peptide 234-246 elicit a
      strikingly immunodominant Th-1-polarized response in C3H and CBA mice, which are
      H-2k strains characterized by severe egg-induced immunopathology. Two additional
      recently described T cell-sensitizing egg antigens are Schistosoma mansoni
      phosphoenolpyruvate carboxykinase (Sm-PEPCK) and thioredoxin peroxidase-1 (Sm-TPx
      1). In contrast to Sm-p40, both of these molecules induce a more balanced Th-1/Th
      2 response, and are relatively stronger antigens in C57BL/6 mice, which develop
      smaller egg granulomas. Importantly, Sm-p40 and Sm-PEPCK have demonstrated
      immunogenicity in humans. The findings in the murine model introduce the
      important notion that egg antigens can vary significantly in immunogenicity
      according to the host's genetic background. A better knowledge of the principal
      immunogenic egg components is necessary to determine whether the immune responses
      to certain antigens can serve as indicators or predictors of the form and
      severity of clinical disease, and to ascertain whether such responses can be
      manipulated for the purpose of reducing pathology.

PMID- 11586424
TI  - Information and education in schistosomiasis control: an analysis of the
      situation in the State of Minas Gerais, Brazil.
AB  - This paper presents the main ideas discussed in the round-table "Social and
      Educational Aspects of Schistosomiasis Control", during the VII International
      Symposium of Schistosomiasis. Considering the perspectives of schistosomiasis
      control in Brazil, it is described the example of the State of Minas Gerais,
      where the disease has been registered for more than seven decades. The importance
      of an extensive evaluation is now more important, considering the recent change
      in the Brazilian health system, since the Federal responsibility for the tropical
      diseases control programs have been replaced by the municipalities coordination.
      In this way, it is urgent to develop effective alternatives to assist the
      municipal staffs in the control task. In the specific case of health education,
      one observes a wide gap between the planned objectives and what is in fact
      carried out. Instant objectives and the utilization of traditional techniques
      prevail, which do not take into account the active participation of the
      population involved. Based on the authors' experience in the scientific and
      health education, the paper analyzes: (1) some data from a case study in the
      metropolitan region of Belo Horizonte, which presents the social representation
      and perception of schistosomiasis by the population; (2) an analysis of 35
      different informative and educative materials used in Brazil since the sixties,
      and (3) some recommendations resulted from the studies that were carried out.

PMID- 11586425
TI  - Recent studies on Schistosoma intercalatum: taxonomic status, puzzling
      distribution and transmission foci revisited.
AB  - Schistosoma intercalatum, which causes human rectal schistosomiasis in Africa,
      still presents a great interest for its imprecise taxonomic status and its
      puzzling distribution in Africa. Two geographically isolated strains of S.
      intercalatum are recognized, the Lower Guinea strain and the Congo strain, which
      differ from each other in a number of morphological, biological and biochemical
      characteristics. Recent molecular data using RAPD markers indicate high
      divergence between the two strains, with values of Nei and Li's similarity index
      allowing recognition of two genetically distinct taxa: experiments on pre- and
      post-isolating mechanisms are in progress in order to re-evaluate the taxonomic
      status of this polytypic species. With regard to its geographical distribution,
      S. intercalatum is characterized by the existence of two stable endemic areas
      (localized in Lower Guinea and North East of Democratic Republic of Congo) which
      correspond to the historical areas of species discovery, and the emergence during
      the last 15 years of new foci of the Lower Guinea strain outside previously known
      endemic areas. The absence of local adaptation of the Lower Guinea strain to its
      intermediate host, supported by experimental studies, may help to facilitate the
      spread of this strain. Nevertheless, the present restricted distribution of this
      species remains puzzling, because its potential snail hosts (bulinids) are widely
      distributed throughout much of Africa. Recent experimental and epidemiological
      studies suggest that interspecific sexual interactions between human schistosomes
      could have a role in limiting the distribution of S. intercalatum: the
      competitive sexual processes acting among human schistosomes show that S.
      haematobium and S. mansoni are always competitively dominant over S.
      intercalatum. These epidemiological observations lead the authors to distinguish
      three kinds of transmission foci for S. intercalatum.

PMID- 11586426
TI  - Genetic epidemiology of fecal egg excretion during Schistosoma mansoni infection
      in an endemic area in Minas Gerais, Brazil.
AB  - There is considerable variation in the level of fecal egg excretion during
      Schistosoma mansoni infections. Within a single endemic area, the distribution of
      egg counts is typically overdispersed, with the majority of eggs excreted coming
      from a minority of residents. The purpose of this study was to quantify the
      influence of genetic factors on patterns of fecal egg excretion in a rural study
      sample in Brazil. Individual fecal egg excretions, expressed in eggs per gram of
      feces, were determined by the Kato-Katz method on stool samples collected on
      three different days. Detailed genealogic information was gathered at the time of
      sampling, which allowed assignment of 461 individuals to 14 pedigrees containing
      between 3 and 422 individuals. Using a maximum likelihood variance decomposition
      approach, we performed quantitative genetic analyses to determine if genetic
      factors could partially account for the observed pattern of fecal egg excretion.
      The quantitative genetic analysis indicated that between 21-37% of the variation
      in S. mansoni egg counts was attributable to additive genetic factors and that
      shared environment, as assessed by common household, accounted for a further 12
      21% of the observed variation. A maximum likelihood heritability (h2) estimate of
      0.44 +/- 0.14 (mean +/- SE) was found for the 9,604 second- and higher-degree
      pairwise relationships in the study sample, which is consistent with the upper
      limit (37%) of the genetic factor determined in the variance decomposition
      analysis. These analyses point to the significant influence of additive host
      genes on the pattern of S. mansoni fecal egg excretion in this endemic area.

PMID- 11586427
TI  - The distribution of Biomphalaria spp. in different habitats in relation to
      physical, biological, water contact and cognitive factors in a rural area in
      Minas Gerais, Brazil.
AB  - A total of 256 sites in 11 habitats were surveyed for Biomphalaria in Melquiades
      rural area (State of Minas Gerais) in August and November 1999 and in March 2000.
      Of the 1,780 Biomphalaria collected, 1,721 (96.7%) were B. glabrata and 59 (3.3%)
      B. straminea. Snails were found in all habitats except in wells, with the largest
      mean numbers in tanks, seepage ponds and canals, and the smallest numbers in
      springs, rice fields and fishponds. People's knowledge of the occurrence of
      Biomphalaria at the collection sites and the presence of Biomphalaria ova were
      strongly correlated with the occurrence of snails, and distance between houses
      and collection sites, as well as water velocity were inversely correlated with
      Biomphalaria occurrence (p < 0.001). The strongest predictor o f Biomphalaria
      occurrence was the presence of tilapia fish in fishponds. Fourteen Biomphalaria
      (0.8% of all snails) found at 6 sites were infected with Schistosoma mansoni.
      Suggestions are made for the utilization of local people's knowledge in snail
      surveys and further studies are recommended on the possible use of tilapia for
      biological control of Biomphalaria in fishponds, as well as modeling of S.
      mansoni transmission and reinfection.

PMID- 11586428
TI  - Invading freshwater snails and biological control in Martinique Island, French
      West Indies.
AB  - Eight alien freshwater snail species were introduced into Martinique Island
      during the last 50 years. The introduced snails include four planorbids
      (Biomphalaria straminea, Helisoma duryi, Amerianna carinata and Gyraulus sp.),
      three thiarids (Melanoides tuberculata, M. amabilis and Tarebia granifera) and
      one ampullarid (Marisa cornuarietis). Four of these species rapidly colonized the
      whole Martinican hydrographic system whereas the other four remained restricted
      to some particular sites. The invasion processes were documented during the last
      20 years and showed (i) a rapid invasion of the island by several morphs of M.
      tuberculata at the beginning of the 80's; (ii) the introduction of T. granifera
      in 1991 and M. amabilis in 1997; and (iii) the rapid spread of these last two
      species throughout the island. In the years following its introduction, M.
      tuberculata was used in biological control experiments against the snail hosts of
      schistosomiasis, B. glabrata and B. straminea. Experiments were conducted with
      success in several groups of water-cress beds which constituted the latest
      transmission sites for schistosomiasis at the beginning of the 80's. A
      malacological survey carried out in 2000 all over the island showed the absence
      of B. glabrata but the presence of some residual populations of B. straminea.
      Long-term studies carried out in Martinique have shown that the thiarids are able
      to maintain relatively stable populations over a long period of time, thus
      preventing recolonization by the snail hosts. Within this context the invasion of
      the hydrographic system of Martinique by thiarid snails has resulted in an
      efficient and sustainable control of the intermediate hosts of schistosomiasis.

PMID- 11586429
TI  - Studies on the biology of schistosomiasis with emphasis on the Senegal river
      basin.
AB  - The construction of the Diama dam on the Senegal river, the Manantali dam on the
      Bafing river, Mali and the ensuing ecological changes have led to a massive
      outbreak of Schistosoma mansoni in Northern Senegal, associated with high
      intensity of infections, due to intense transmission, and the creation of new
      foci of S. haematobium. Data on the vectorial capacity of Biomphalaria pfeifferi
      from Ndombo, near Richard Toll, Senegal are presented with sympatric and
      allopatric (Cameroon) S. mansoni. Comparisons are made on infectivity, cercarial
      production, chronobiology of cercarial emergence and longevity of infected
      snails. Recent data on the intermediate host specificity of different isolates of
      S. haematobium from the Lower and Middle Valley of the Senegal river basin (SRB)
      demonstrate the existence of at least two strains of S. haematobium. The role of
      Bulinus truncatus in the transmission of S. haematobium in the Lower and Middle
      Valleys of the SRB is reviewed. Both S. haematobium and S. mansoni are
      transmitted in the same foci in some areas of the SRB.

PMID- 11586430
TI  - Preliminary analysis of Sm14 in distinct fractions of Schistosoma mansoni adult
      worm extract.
AB  - In previous studies it was shown that the recombinant molecule, r-Sm14, induces
      high levels of protection against Schistosoma mansoni infection in two outbred
      animal models and immune crossprotection against infection by Fasciola hepatica
      in Swiss outbred mice. r-Sm14 was derived from a living worm extract, called SE,
      and is being developed as the molecular basis of an anti-helminth bivalent
      vaccine against the two parasites, for medical and veterinary application.
      Present data refer to SDS-PAGE and Western Blotting analysis of four different
      preparations of S. mansoni adult worms focusing Sm14 identification. The extracts
      correspond to the initial fraction of the SE extraction process, containing
      products released by living worms (SEi); SE2, reextraction of adult worms in PBS;
      and SE of separated male and female adult worms. In all extracts it was possible
      to detect the component of 14 kDa, that was recognized by specific anti-rSm14
      antibody raised in rabbits.

PMID- 11586431
TI  - Control of calcium homeostasis in Schistosoma mansoni.
AB  - Calcium signalling is fundamental for muscular contractility of Schistosoma
      mansoni. We have previously described the presence of transport ATPases (Na+,K+
      ATPase and (Ca2+-Mg2+)-ATPase) and calcium channels (ryanodine receptors - RyR)
      involved in control of calcium homeostasis in this worm. Here we briefly review
      the main technics (ATPase activity, binding with specific radioligands, fluxes of
      45Ca2+ and whole worm contractions) and results obtained in order to compare the
      distribution patterns of these proteins: thapsigargin-sensitive (Ca2+-Mg2+)
      ATPase activity and RyR co-purified in P1 and P4 fractions mainly, which is
      compatible with a sarcoplasmic reticulum localization, while basal ATPase (along
      with Na+,K+-ATPase) and thapsigargin-resistant (Ca2+-Mg2+)-ATPase have a distinct
      distribution, indicative of their plasma membrane localization. Finally we
      attempt to integrate these contributions with data from other groups in order to
      propose the first synoptic model for control of calcium homeostasis in S.
      mansoni.

PMID- 11586432
TI  - T cell clones from Schistosoma haematobium infected and exposed individuals
      lacking distinct cytokine profiles for Th1/Th2 polarisation.
AB  - T cell clones were derived from peripheral blood mononuclear cells of Schistosoma
      haematobium infected and uninfected individuals living in an endemic area. The
      clones were stimulated with S. haematobium worm and egg antigens and purified
      protein derivative. Attempts were made to classify the T cell clones according to
      production of the cytokines IL-4, IL-5 and IFN-gamma. All the T cell clones
      derived were observed to produce cytokines used as markers for the classification
      of Th1/Th2 subsets. However, the 'signature' cytokines marking each subset were
      produced at different levels. The classification depended on the dominating
      cytokine type, which was having either Th0/1 or Th0/2 subsets. The results
      indicated that no distinct cytokine profiles for polarisation of Th1/Th2 subsets
      were detected in these S. haematobium infected humans. The balance in the
      profiles of cytokines marking each subset were related to infection and re
      infection status after treatment with praziquantel. In the present study, as
      judged by the changes in infection status with time, the T cell responses
      appeared to be less stable and more dynamic, suggesting that small quantitative
      changes in the balance of the cytokines response could result in either
      susceptibility or resistant to S. haematobium infection.

PMID- 11586433
TI  - Preliminary results on the effects of CD40/CD40L interactions and SAC-induction
      on IFN-gamma expression in human schistosomiasis.
AB  - In this communication the authors analyzed the pattern of expression of IFN-gamma
      as a surrogate type 1 response in different clinical forms of schistosomiasis in
      response to stimulation involving T-cell dependent and T-cell independent
      pathways, to investigate which pathways were functional in human schistosomiasis,
      and to further characterize the nature of Th1 response impairment in this
      parasitic disease.

PMID- 11586434
TI  - Quantitative and qualitative interferences of pentoxifillyne on hepatic
      Schistosoma mansoni granulomas: effects on extracellular matrix and eosinophil
      population.
AB  - Mast cells and eosinophils actively participate in tissue repair and are
      prominent components of Schistosoma mansoni granulomas. Since pentoxifillyne
      (PTX) is an immunomodulatory and antifibrotic substance, we aimed to
      characterize, by morphological techniques, the effect of this drug on fibrosis
      developed inside murine hepatic schistosomal granulomatous reaction, beyond the
      quantification of eosinophil and mast cell populations. The drug (1 mg/100 g
      animal weight) was administrated from 35 to 90 days post-infection, when the
      animals were killed. The intragranulomatous interstitial collagen network was
      analyzed by confocal laser scanning microscopy, the number of eosinophils and
      mast cells was quantified and the results were validated by t-student test.
      Treatment did not interfere on the granuloma evolution but caused a significant
      decrease in the total and involutive number of hepatic granulomas (p = 0.01 and
      0.001, respectively), and in the intragranulomatous accumulation of eosinophils
      (p = 0.0001). Otherwise, the number of mast cells was not significantly altered
      (p = 0.9); however, it was positively correlated with the number of granulomatous
      structures (r = 0.955). In conclusion, PTX does not affect development and
      collagen deposition in S. mansoni murine granuloma, but decreases the
      intragranulomatous eosinophil accumulation possibly due to its immunomodulatory
      capability, interfering in cellular recruitment and/or differentiation.

PMID- 11586435
TI  - Surgical hepatosplenic mansonic schistosomiasis in adolescents: repercussions of
      the post-treatment schistosomotic burden on the hepatic functional reserve.
AB  - Schistosomiasis mansoni affects the hepatic functional reserve. Clinical
      treatment with oxamniquine is not 100% effective and there has been found strain
      of this parasite resistant to this drug. The aims of this investigation were: (1)
      to examine the presence of residual parasite burden after medical and surgical
      treatment on adolescents with surgical schistosomiasis mansoni and (2) to assess
      the effect on the hepatic functional reserve in patients with and without
      residual infection. Twenty nine children with hepatosplenic schistosomiasis
      mansoni and bleeding esophageal varices were treated with oxamniquine. They
      underwent splenectomy, ligature of the left gastric vein and autologous
      implantation of spleen tissue into the greater omentum. After a mean post
      operative follow up of five years they underwent rectal biopsy for schistosomotic
      egg search. They were divided in patients with and without infection. In 20
      patients the submucosal egg search was negative, however, in 9 it was positive.
      The hepatic functional reserve in the patients without infection was as follows:
      17 were Child-Pugh A and 3 Child-Pugh B. In the patients who were still infected
      6 were Child-Pugh A and 3 Child-Pugh B. The chi2 analysis of the hepatic
      functional reserve showed chi2 = 3.19 - p= 0.07. From the results the following
      conclusion can be drawn: residual infection or reinfection in the follow up
      period had not interfered with the distribution of the hepatic functional reserve
      of the patients in this series. However, there was a trend for a decrease of this
      parameter in patients with residual infection.

PMID- 11586436
TI  - Autotransplant of spleen tissue in children with schistosomiasis: evaluation of
      splenic function after splenosis.
AB  - Autotransplantation of spleen tissue has been done, in the past ten years, in
      children with schistosomiasis mansoni with bleeding varices. The purposes of this
      investigation were: (1) to study the morphology and function of the remnant
      spleen tissue; (2) to quantify the production of tuftsin; and (3) to assess the
      immune response to pneumococcal vaccine of these patients. Twenty three children,
      who underwent splenectomy and autologous implantation of spleen tissue into the
      greater omentum were included in this investigation. The average postoperative
      follow-up is five years. Splenosis was proved by colloid liver-spleen scans.
      Search for Howell-Jolly bodies assessed the filtration function. Tuftsin and the
      titer of pneumococcal antibodies were quantified by ELISA. Splenosis was evident
      in all children; however, it was insufficient in two. Howell-Jolly bodies were
      found only in these two patients. The mean tuftsin serum concentration (335.0 +/-
      29.8 ng/ml) was inside the normal range. The immune response to pneumococcal
      vaccination was adequate in 15 patients; intermediate in four; and inadequate in
      four. From the results the following conclusions can be drawn: splenosis was
      efficient in maintaining the filtration splenic function in more than 90% and
      produced tuftsin inside the range of normality. It also provided the immunologic
      splenic response to pneumococcal vaccination in 65% of the patients of this
      series.

PMID- 11586437
TI  - Cloning and characterization of SmZF1, a gene encoding a Schistosoma mansoni zinc
      finger protein.
AB  - The zinc finger motifs (Cys2His2) are found in several proteins playing a role in
      the regulation of transcripton. SmZF1, a Schistosoma mansoni gene encoding a zinc
      finger protein was initially isolated from an adult worm cDNA library, as a
      partial cDNA. The full sequence of the gene was obtained by subcloning and
      sequencing cDNA and genomic fragments. The collated gene sequence is 2181 nt and
      the complete cDNA sequence is 705 bp containing the full open reading frame of
      the gene. Analysis of the genome sequence revealed the presence of three introns
      interrupting the coding region. The open reading frame theoretically encodes a
      protein of 164 amino acids, with a calculated molecular mass of 18,667Da. The
      predicted protein contains three zinc finger motifs, usually present in
      transcription regulatory proteins. PCR amplification with specific primers for
      the gene allowed for the detection of the target in egg, cercariae,
      schistosomulum and adult worm cDNA libraries indicating the expression of the
      mRNA in these life cycle stages of S. mansoni. This pattern of expression
      suggests the gene plays a role in vital functions of different life cycle stages
      of the parasite. Future research will be directed to elucidate the functional
      role of SmZF1.

PMID- 11586438
TI  - r-Sm14 - pRSETA efficacy in experimental animals.
AB  - Previous studies carried out with Sm14 in experimental vaccination against
      Schistosoma mansoni or Fasciola hepatica infections were performed with
      recombinant Sm14 (rSm14) produced in Escherichia coli by the pGEMEX system
      (Promega). The rSm14 was expressed as a 40 kDa fusion protein with the major
      bacteriophage T7 capsid protein. Vaccination experiments with this rSm14 in
      animal models resulted in consistent high protective activity against S. mansoni
      cercariae challenge and enabled rSm14 to be included among the vaccine antigens
      endorsed by the World Health Organization for phase I/II clinical trials. Since
      the preparation of pGEMEX based rSm14 is time consuming and results in low yield
      for large scale production, we have tested other E. coli expression systems which
      would be more suitable for scale up and downstream processing. We expressed two
      different 6XHis-tagged Sm14 fusion proteins in a T7 promoter based plasmids. The
      6XHis-tag fusions allowed rapid purification of the recombinant proteins through
      a Ni+2-charged resin. The resulted recombinant 18 and 16 kDa proteins were
      recognized by anti-Sm14 antibodies and also by antiserum against adult S. mansoni
      soluble secreted/excreted proteins in Western-Blot. Both proteins were also
      protective against S. mansoni cercariae infection to the same extent as the rSm14
      expressed by the pGEMEX system.

PMID- 11586439
TI  - Schistosomal myeloradiculopathy due to Schistosoma mansoni: report on 23 cases.
AB  - Schistosoma mansoni infection is likely to be responsible for a significant
      proportion of cases of myelopathy occurring in areas where schistosomiasis is
      endemic. The aim of this study is to describe the clinical, laboratory and
      therapeutic data of 23 patients with schistosomal myeloradiculopathy. The medical
      records of 23 patients with schistosomal myelopathy admitted to two general
      hospitals of Belo Horizonte (MG), in Brazil, from 1995 to 1999, were reviewed
      retrospectively. Seventeen patients were male (74%). The mean age for the whole
      group was 27 years. Lower limb weakness and associated lumbar and/or lower limb
      pain were reported by 20 patients (87%), and 16 (70%) were unable to walk. All
      individuals presented urinary retention and 19 (83%) complained of intestinal
      dysfunction. The treatment was based on the association of antischistosomal drugs
      and corticosteroids. Five patients (22%) presented a full response to treatment,
      13 (57%) partial response without functional limitations and 4 (17%) partial
      improvement with limitations or no response. Three out of the 4 patients who
      stopped steroids before 45 days of treatment developed recurrence of the symptoms
      and signs of myelopathy. Our cases demonstrate the severe presentation of the
      disease and the data disclosed here suggest that treatment with steroids should
      be kept for months after clinical improvement.

PMID- 11586440
TI  - Schistosomiasis mansoni is associated with pyogenic liver abscesses in the state
      of Minas Gerais, Brazil.
AB  - The association between pyogenic liver abscesses and schistosomiasis has been
      confirmed by clinical and experimental studies. In this retrospective study of 78
      patients with pyogenic liver abscesses the association with schistosomiasis has
      been investigated. Pyodermitis, a known focus of bacteremia, was observed in 19
      patients (24%). Blood eosinophilia was observed in 30 patients (39%).
      Staphylococcus aureus was cultured from abscesses in 17 out of 38 patients (45%).
      Forty-one out of 57 patients (53%) had stool examination. Schistosoma mansoni was
      the main parasite identified. Eggs of S. mansoni were also identified in liver
      biopsies in 7 out of 19 patients who did the exam. The large number of young
      patients with liver abscesses described here is different from what has been
      observed in developed countries. This clinical study provide support for the
      concept that granulomas of S. mansoni in the liver are foci for colonization with
      S. aureus, which in presence of staphylococcal bacteremia can form liver
      abscesses.

PMID- 11586441
TI  - Hepatosplenic schistosomiasis in field-based studies: a combined clinical and
      sonographic definition.
AB  - A combined clinical and sonographic classification of hepatosplenic
      schistosomiasis mansoni to be used in field-based studies is proposed herein.
      Seven hundred forty one individuals out of 892 (83%), living in an area endemic
      for schistosomiasis in Brazil, have been submitted to clinical and ultrasound
      examinations. Based on two stool examinations the overall prevalence for
      schistosomiasis in this area was 73%. Abdominal palpation was performed with
      patients in dorsal decubit, during deep breath, by two experienced physicians and
      a portable ultrasound was used for the evaluation of liver fibrosis, portal
      collaterals and spleen size. Four groups of individuals were identified using
      data obtained by abdominal palpation and ultrasound examination: (1) palpable
      spleen and intense periportal thickening in 9 individuals (1.2%); (2) spleen not
      palpable and intense periportal thickening in 15 (2%); (3) palpable spleen with
      light to moderate periportal thickening in 32 (4.3%), and (4) palpable spleen
      with a normal liver on ultrasound in 30 (4%). The definition of hepatosplenic
      schistosomiasis in field-based studies as the finding of Schistosoma mansoni eggs
      in the stools in an individual with splenomegaly is not acceptable anymore.
      Abdominal ultrasound should be combined with clinical examination to accurately
      identify hepatosplenics in endemic areas for schistosomiasis.

PMID- 11586442
TI  - Report of the second satellite symposium on ultrasound in schistosomiasis.
AB  - A group of experts on schistosomiasis and ultrasonography discussed the
      experiences and results obtained with the Niamey-Belo Horizonte Protocol on
      Ultrasonography in Schistosomiasis. A series of recommendations about qualitative
      and quantitative data obtained by ultrasound in studies performed in Africa and
      Brazil are presented. Immunological, genetic and epidemiological studies must
      rely on ultrasound for the identification of patients with periportal
      thickening/fibrosis.

PMID- 11586443
TI  - The impact of repeated treatment with praziquantel of schistosomiasis in children
      under six years of age living in an endemic area for Schistosoma haematobium
      infection.
AB  - Praziquantel was given every eight weeks for two years to children aged under six
      years of age, living in a Schistosoma haematobium endemic area. Infection with S.
      haematobium and haematuria were examined in urine and antibody profiles (IgA,
      IgE, IgM, IgG1, IgG2, IgG3, and IgG4) against S. haematobium adult worm and egg
      antigens were determined from sera collected before each treatment. Chemotherapy
      reduced infection prevalence and mean intensity from 51.8% and 110 eggs per 10 ml
      urine, respectively, before starting re-treatment programme to very low levels
      thereafter. Praziquantel is not accumulated after periodic administration in
      children. Immunoglobulin levels change during the course of treatment with a
      shift towards 'protective' mechanisms. The significant changes noted in some
      individuals were the drop in 'blocking' IgG2 and IgG4 whereas the 'protecting'
      IgA and IgG1 levels increased. The antibody profiles in the rest of the children
      remained generally unchanged throughout the study and no haematuria was observed
      after the second treatment. The removal of worms before production of large
      number of eggs, prevented the children from developing morbidity.

PMID- 11586444
TI  - Replacing oxamniquine by praziquantel against Schistosoma mansoni infection in a
      rural community from the sugar-cane zone of Northeast Brazil: an epidemiological
      follow-up.
AB  - A group of 52 villagers was followed-up for three years regarding Schistosoma
      mansoni infection. All villagers were periodically surveyed by the Kato-Katz
      method. In March 1997 and March 1998 the positives were treated with oxamniquine
      (15-20 mg/kg), and in March 1999, with praziquantel (60 mg/kg). All infection
      indices decreased substantially between March 1999 and March 2000: prevalence of
      infection (from 32.7% to 21.2%), prevalence of moderate/heavy infection (from
      7.7% to 1.9%), intensity of infection (from 23.1 epg to 7.4 epg) and reinfection
      (from 35.7% to 14.3%). Negativation increased from 53.8 to 82.4. An optimistic
      prognostic is assumed in the short term for the introduction of praziquantel in
      the study area.

PMID- 11586445
TI  - Specific situations related to acute schistosomiasis in Pernambuco, Brazil.
AB  - The present work reports on two epidemiological episodes resulting in acute
      schistosomiasis involving wealthy persons living in the State of Pernambuco,
      Brazil. The authors discuss the epidemiological, clinical and serologic
      characteristics of the acute infections and also the way in which the conditions
      for transmission occurred.

PMID- 11586446
TI  - Possible competitive displacement of planorbids by Melanoides tuberculata in
      Minas Gerais, Brazil.
AB  - Several species of snails, including Pomacea haustrum, Marisa cornuarietis and
      Helisoma duryi, have been identified as probable competitors and/or predators of
      planorbid intermediate hosts of Schistosoma. During the last few years, studies
      carried out in the Caribbean region have shown reductions and even disappearances
      of populations of Biomphalaria glabrata and B. straminea in breeding places where
      the snail Melanoides tuberculata was introduced. Observations made over a period
      of 10 years in two lakes close to Belo Horizonte, MG, showed that there were
      marked reductions in autochthonous populations of B. glabrata and B. straminea
      after the arrival of M. tuberculata, both Biomphalaria species disappearing
      completely after eight years.

PMID- 11586447
TI  - Freshwater snails and schistosomiasis mansoni in the State of Rio de Janeiro,
      Brazil: I-- Metropolitan mesoregion.
AB  - In order to elaborate a planorbid chart of the State of Rio de Janeiro a survey
      of freshwater gastropods in the Metropolitan Mesoregion of this State was
      performed and revealed the occurrence of 20 species: Antillorbis nordestensis
      (Lucena, 1954); Biomphalaria glabrata (Say, 1818); Biomphalaria schrammi (Crosse,
      1864); Biomphalaria straminea (Dunker, 1848); Biomphalaria tenagophila (Orbigny,
      1835); Burnupia sp.; Drepanotrema anatinum (Orbigny, 1835); Drepanotrema cimex
      (Moricand, 1839); Drepanotrema lucidum (Pfeiffer, 1839); Ferrissia sp.;
      Gundlachia ticaga (Marcus & Marcus, 1962); Heleobia davisi Silva & Thome, 1985;
      Lymnaea columella Say, 1817; Melanoides tuberculatus (Muller, 1774); Physa
      cubensis Pfeiffer, 1839; Physa marmorata Guilding, 1828; Pomacea sp.; Pomacea
      canaliculata (Lamarck, 1822); Pomacea lineata (Spix, 1827) and Pomacea sordida
      (Swainson, 1823). Among the planorbid species B. tenagophila was the most
      frequent, occurring in all municipalities surveyed. The present study extends the
      distribution of B. straminea in the State of Rio de Janeiro and reports new
      records for A. nordestensis, B. schrammi, G. ticaga, H. davisi and the genera
      Burnupia and Ferrissia. An account about the current transmission areas of
      schistosomiasis mansoni in this Mesoregion is presented as well.

PMID- 11586448
TI  - Infection by Schistosoma mansoni Sambon 1907 in the first four months of life of
      Biomphalaria straminea (Dunker, 1848) in Brazil.
AB  - Compatibility between Schistosoma mansoni and Biomphalaria straminea when exposed
      to the parasite on the first four months of age was assessed for five
      parasitological aspects: indices of infection and mortality, duration of
      precercarial and cercarial periods, and rate of cercarial emission. Infections
      were made on molluscs from laboratory colonies, at the following ages: 8, 13, 18,
      21, 53, 83 and 114 days. Two B. straminea colonies were used (Camorim, PE and
      Picos, PI), and one B. glabrata colony (Ressaca, MG) was used as control. The
      main results are as follows: (I) infection was significantly associated with
      mollusc age, being proportionally higher in sexually immature than in mature
      molluscs for the three colonies; (II) for B. straminea from Camorim, mortality
      did not differ significantly between infected and non-infected snails; for B.
      straminea from Picos significantly more deaths occurred among infected than among
      non-infected snails, while the opposite was observed for B. glabrata from
      Ressaca; (III) for the three colonies, the precercarial period was significantly
      shorter for immature molluscs than for mature ones; (IV) the duration of the
      cercarial period was extremely variable for the three colonies; (V) sexual
      maturity did not influence cercarial emission for the three colonies.

PMID- 11586449
TI  - Changes on Schistosoma mansoni (Digenea: Schistosomatidae) worm load in Nectomys
      squamipes (Rodentia: Sigmodontinae) concurrently infected with Echinostoma
      paraensei (Digenea: Echinostomatidae).
AB  - The water rat, Nectomys squamipes, closely involved in schistosomiasis
      transmission in Brazil, has been found naturally infected simultaneously by
      Schistosoma mansoni and Echinostoma paraensei. Laboratory experiments were
      conducted to verify parasitic interaction in concurrent infection. It was
      replicated four times with a total of 42 water rats and essayed two times with 90
      mice pre-infected with E. paraensei. Rodents were divided into three groups in
      each replication. A wild strain recently isolated from Sumidouro, RJ, and a
      laboratory strain of S. mansoni from Belo Horizonte (BH) was used. Rats infected
      with E. paraensei were challenged 4 weeks later with S. mansoni and mice 2 or 6
      weeks after the infection with S. mansoni. Necropsy took place 8 weeks following
      S. mansoni infection. The N. squamipes treatment groups challenged with S.
      mansoni RJ strain showed a significant decrease (80 and 65%) in the S. mansoni
      parasite load when compared with their respective control groups. There was a
      significant change or no change in the hosts challenged with the BH strain. The
      persistence time of E. paraensei within host was extended in relation to control
      groups, with a consequent enhancement of the number of recovered worm. An E.
      paraensei strain-specific influence on S. mansoni parasitism is reported. This
      paper presents some experimental data about this interaction in N. squamipes and
      Mus musculus.

PMID- 11586450
TI  - Carotid arteriography impacts carotid stenosis management.
AB  - Recent literature advocates carotid endarterectomy on duplex alone. The authors
      hypothesized that carotid angiography adds information that alters clinical
      management in a substantial number of patients compared to the use of carotid
      duplex examination alone. The records of 182 consecutive patients who underwent
      carotid artery duplex and subsequent carotid/cerebral angiography for suspected
      carotid artery stenosis between January 1998 and April 1999 were reviewed
      retrospectively. Carotid artery duplex examinations were stratified based on
      stenosis: < or =39%, 40% to 59%, 60% to 79% (moderate), 80% to 99% (severe),
      100%. Carotid stenosis on angiograms was determined by NASCET criteria. New
      information found at angiography included vertebral, subclavian, or arch
      atherosclerosis, intracranial pathosis, or a change in duplex stenosis category
      to a degree of stenosis not requiring surgery. Clinical importance was attributed
      to angiograms that altered the patients' management plan. Angiography provided
      additional information in 53% (97/182) of patients. Vertebral disease was found
      in 25.1%, subclavian disease in 16.4%, intracranial disease in 15.3%, aortic arch
      disease in 3.3%. Patient treatment was altered in 30% (55/182). Angiographic
      findings downgraded the stenosis to medical therapy in 20.9% (38/182). The
      surgical plan was influenced in 5.5% (10/182). Nine intracranial aneurysms were
      discovered. Carotid angiography was essential for vascular bypass surgery
      planning in 3.3% (6/182). Angioplasty was performed in 2.2% (4/182). The accurate
      determination of stenosis is critical in determining optimal treatment of
      patients with carotid artery stenosis. Routine carotid angiography remains
      valuable in the clinical treatment of these patients.

PMID- 11586451
TI  - Double-layer everted saphenous vein patch angioplasty for carotid endarterectomy.
AB  - Saphenous vein patch angioplasty is the preferred method of closure of the
      arteriotomy site during carotid endarterectomies. A major early complication of
      the saphenous vein patch is rupture of the patch which can occur within the first
      few postoperative days. The reported incidence varies from 0.5% to 4%. Patch
      rupture can result in stroke or death. From May 1992 to April 1999, autogenous
      everted double-layer saphenous vein patch was used in 192 carotid
      endarterectomies performed on 168 patients; 96 males and 72 females. The age
      range was from 54 to 94 years with a mean age of 73 years. The saphenous vein is
      harvested from the ankle. It is everted and then used as a double-layer patch.
      The follow-up period was from 3 to 74 months, with a mean of 24 months.
      Postoperatively, there were no patch ruptures or late aneurysm formation. There
      was no perioperative mortality. Everted double-layer saphenous vein patch
      eliminates the risk of patch rupture and at the same time retains the benefits of
      an autologous nonprosthetic graft. Saphenous vein from the ankle can be safely
      used for carotid angioplasty as a double layer patch.

PMID- 11586452
TI  - Balloon-expandable common iliac artery occluder device for endovascular aneurysm
      repair.
AB  - This study was performed to evaluate the efficacy of a balloon-expandable Palmaz
      stent common iliac artery occluder device for endovascular stent-graft repair of
      aortoiliac aneurysms. Eighty-four patients (79 men, 5 women; age range 60-95 yr;
      mean age, 76 yr) with aortoiliac aneurysms underwent endovascular stent-graft
      repair. The repair consisted of a stent-graft extending from the abdominal aorta
      to the iliac or common femoral artery, a cross-femoral bypass graft, and an
      endovascular arterial occluder device within the contralateral common iliac
      artery. The occluder device consisted of a 5-cm segment of 6-mm diameter
      polytetrafluoroethylene (PTFE) graft with a purse-string suture occluding the
      leading end and a Palmaz stent sutured to the trailing end. The occluder device
      was delivered through a 17F catheter via an arteriotomy. Eighty-three of the 84
      patients received aortic endografts. In one case, infrarenal aortic rupture
      occurred during deployment of the aortic stent requiring conversion to an open
      surgical repair. Initial technical success for occluder device insertion was
      achieved in 78 of the remaining 83 patients. Failure to advance the occluder
      device delivery sheath through a diseased iliac artery occurred in one patient.
      Common iliac artery rupture occurred during balloon expansion and occluder device
      deployment in two patients. Two patients required additional coil embolization of
      the common iliac artery adjacent to the occluder device at the time of stent
      graft insertion to correct incomplete iliac occlusion. Delayed occluder device
      related complications included one patient with a postoperative iliac endoleak
      who required percutaneous coil embolization and one patient with a postoperative
      iliac endoleak in whom a contained aortic aneurysm rupture developed that was
      treated by surgical ligation of the common iliac artery. Use of the Palmaz stent
      based iliac artery occluder device is an effective technique to induce common
      iliac artery thrombosis to facilitate endoluminal stent-graft aneurysm repair.

PMID- 11586453
TI  - Correlation of Tc-99m-red blood cell phleboscintigraphy with clinical severity of
      chronic venous disease.
AB  - Equilibrium red blood cell phleboscintigraphy of the lower limbs for the
      diagnostic management of chronic venous disease has been proposed. The aim of
      this study was to verify the correlation of the phleboscintigraphic assessment of
      chronic venous disease with the clinical grading of the severity of the disease,
      since other diagnostic modalities have been recently demonstrated a poor and only
      partial correlation. Equilibrium Tc-99m-red blood cell phleboscintigraphy was
      performed in 27 patients with chronic venous disease. Scintigraphic images of 52
      limbs were classified according to a four-class qualitative grading of the
      severity of the venous disease, and a quantitative scintigraphic index (saphena
      /femoral ratio) was assigned to each limb. The scintigraphic qualitative grading
      showed a highly significant correlation with the clinical grading (Rs=0.82,
      p<0.01), a good interobserver and intraobserver agreement (86.5% and 92.3%,
      respectively) and more than 90% sensitivity and specificity to identify the
      categories "minimal or no chronic venous disease" or "more significant disease"
      (assessed according to the Bayes theorem). Sensitivity and specificity results
      for the quantitative assessment were not as good. Phleboscintigraphy correlates
      well with the clinical grading of the severity of chronic venous disease of the
      lower limbs and may have potential as a valuable diagnostic tool for the
      noninvasive assessment of chronic venous disease.

PMID- 11586454
TI  - Clinical experience with temporary vena cava filters.
AB  - An experience with temporary filter placement, which seems to be safe and
      effective for temporarily preventing pulmonary embolism, is reported. Since
      October 1997, six patients had temporary filters. There were two men and four
      women, with a mean age of 37 years. Three filters were placed at the infrarenal
      inferior vena cava, two at the suprarenal inferior vena cava, and one at the
      superior vena cava. All filters were placed before various surgical
      interventions. During filter placement, anticoagulation therapy was routinely
      performed. There were no complications at and during filter placement. No
      pulmonary emboli occurred during surgical intervention. All filters were
      successfully removed, two of which were exchanged for permanent filters. All
      patients are alive and well without recurrent deep vein thrombosis and/or
      pulmonary emboli during a follow-up period of 11 to 25 months. Although this
      experience is small, temporary filter placement is safe and effective for short
      term prevention of pulmonary emboli even in older patients or those with
      malignant disease. Veins of the upper part of the body may be more favorable than
      the femoral vein for insertion of a temporary filter. Temporary filters can be
      safely placed not only at the infrarenal inferior vena cava, but also at the
      suprarenal inferior vena cava or superior vena cava.

PMID- 11586455
TI  - Leukocyte/endothelium activation and interactions during femoral percutaneous
      transluminal angioplasty.
AB  - Recent data suggest that leukocyte-endothelium activation/interactions are
      important for restenosis after percutaneous transluminal angioplasty (PTA). Ten
      patients with superficial femoral artery occlusive disease (stage Fontaine IIb)
      were examined after a percutaneous transluminal angioplasty (PTA) versus a
      preceding aortoangiography (AAG). Blood samples from corresponding femoral
      arteries and veins were obtained before, immediately after, and 4 hours after
      each procedure. The authors examined the ex vivo respiratory burst and leukocytic
      expression of adhesion molecules flowcytometrically, adhesion molecule plasma
      concentrations, and inflammatory mediators concentrations in plasma and in
      endotoxin-stimulated whole blood cultures by ELISA, and the leukocyte counts.
      After PTA, venous plasma concentrations of soluble (s)L-selectin (148.2 +/-14.7%,
      p<0.05 vs 100% baseline +/- sem), sP-selectin (130.7 +/-6.9%, p<0.01; sE-selectin
      (117.5 +/-8.3%, p<0.05 vs arterial), sLFA-3 (130.7 +/-15.8%, p<0.05) were
      increased. Expressions of L-selectin (93.0 +/-5.7%, p<0.05 vs arterial), CD11a
      (98.8 +/-3.8%, p=0.06), CD18 (96.9 +/-4.0%, p<0.05 vs arterial), and ICAM-1 (89.1
      +/-7.7%, p<0.05) on polymorphonuclear neutrophils (PMN), and arteriovenous
      leukocyte counts (arterial: 103.5 +/-5.4%, venous: 91.1 +/-3.3%, p<0.05)
      decreased. Venous ex vivo secretions of oxygen radicals (141.4 +/-28.1%, p<0.05
      vs AAG), PMN-elastase (173.7 +/-35.7%, p<0.05 vs AAG), and interleukin (IL)-8
      (226.5 +/-56.4%, p<0.001; p<0.0001 vs AAG), as well as PMN-elastase (173.7 +/
      35.7%, p<0.05 vs AAG) and tumor necrosis factor (TNF)-alpha plasma concentrations
      (124.1 +/-11.9%, p=0.06) rose. Four hours after PTA, a leukocytosis and exhausted
      TNF-alpha (69.8 +/-10.4%, p<0.05) and IL-8 secretions (72.4 +/-4.6%, p<0.01)
      occurred. PTA induced local leukocyte-endothelium activations (stronger ex vivo
      mediator productions) and interactions (decreased venous leukocyte counts,
      increased plasma concentrations, and decreased leukocytic expression of adhesion
      molecules) with the release of inflammatory mediators (higher plasma
      concentrations and exhaustions after 4 hours).

PMID- 11586456
TI  - Clostridial mycotic aneurysm of the thoracoabdominal aorta--a case report.
AB  - Clostridial infection of the aorta is a rare and life-threatening condition. The
      management of a mycotic aneurysm involving the thoracoabdominal aorta due to
      Clostridium septicum infection is presented. Successful surgical management of
      the aortic infection involved arterial resection, wide debridement of the
      surrounding tissues, and in situ graft replacement. Sixteen additional cases of
      clostridial infection of the aortoiliac segment reported in the literature are
      also summarized. In ten of these 17 cases, an associated colonic adenocarcinoma
      was documented.

PMID- 11586457
TI  - An extraluminal leiomyosarcoma of the iliac vein without thrombosis--a case
      report.
AB  - Vascular leiomyosarcoma (LMS)is a rare malignant tumor arising from the muscle
      cells of the media of the vessels. Vascular LMS is often diagnosed as a result of
      the clinical manifestations of impaired venous flow such as edema and
      phlebothrombosis. The authors present a case of an LMS in a 72-year-old woman.
      Physical examination revealed a round mass deep in the left inguinal region close
      to the inguinal vessels, fixed and not pulsating. There was no sign of left lower
      limb edema nor of articular impairment of the hip. Inguinal and distal pulses
      were normal. Results of laboratory analysis, including values for the oncologic
      markers, were normal. An ultrasound scan of the left inguinal fossa showed a 50
      by-30 mm mass of mixed aspect that adhered to the left common iliac artery. An
      echo color Doppler showed conservative arterial flow. Thus, a thrombotic aneurysm
      of the left iliac artery was diagnosed. Chest x-ray showed no pathological
      findings. An abdominal computerized tomograph (CT) scan confirmed the location of
      the neoplasm and revealed a narrowing of the left iliac vein compressed behind
      the mass. The finding was interpreted as a colliquative lymph node. The patient
      underwent explorative laparotomy with midline incision. The finding was a
      neoplastic bilobed mass compressing and infiltrating the left iliac vein with no
      cleavage surface between the mass itself and the venous wall. An intraoperative
      frozen section revealed a necrotic mass with a cortex of ambiguous
      interpretation. Surgical procedure was then finished with no further venous
      resection. Histologic examination revealed the presence of leiomyosarcomatous
      tissue with nuclear pleomorphisms inside necrotic material limited by a thin
      fibrotic capsule. According to Coindre's classification the tumor was a G3. After
      six months the patient is fit and a CT scan showed no evidence of recurring
      disease.

PMID- 11586458
TI  - Intravenous pyogenic granuloma: immunohistochemical consideration--a case report.
AB  - Intravenous pyogenic granuloma is a rare form of pyogenic granuloma in which the
      whole lesion appears as a single polypoid mass projecting into the lumen of a
      vein. Histologically, this benign lesion is similar to pyogenic granuloma of
      other locations and is characterized by lobular proliferation of capillaries
      embedded in a fibromyxoid stroma. The following report illustrated the classic
      findings associated with an intravenous pyogenic granuloma in a young woman. A
      brief review of this rare entity follows the case report. Although the history
      and physical findings were approximately the same in each patient, they do not
      seem characteristic enough to allow for a definite preoperative diagnosis. The
      clinical differential diagnosis of intravenous pyogenic granuloma is varied and
      requires careful pathologic attention if excised. Complete local excision with a
      small portion of the vein is the treatment of choice.

PMID- 11586459
TI  - Transplanting a kidney with a renal artery aneurysm--a case report and literature
      review.
AB  - As a rare postoperative complication, renal artery aneurysm has been reported in
      0.95% of kidney transplants. A renal artery aneurysm was repaired prior to
      transplantation of the kidney.

PMID- 11586460
TI  - Horner's syndrome after carotid endarterectomy--a case report.
AB  - Horner's syndrome is described in a patient with anisocoria and unilateral lid
      ptosis 48 hours after an ipsilateral carotid endarterectomy. This case
      illustrates a rare iatrogenic complication of sympathetic nerve dysfunction
      following elective surgery.

PMID- 11586461
TI  - Mesocaval shunt: patency after 22 years--a case report.
AB  - A case of a mesocaval shunt placed urgently in a 52-year-old man to control life
      threatening hemorrhage from esophageal varices is reported. The latter resulted
      from portal hypertension secondary to Laennec's cirrhosis. The patient suffered
      from acute and chronic alcoholism, but not alcoholic hepatitis. Twenty-three
      years later, the shunt is angiographically patent; the patient is alive and well.
      He has been free from encephalopathy with the exception of three episodes of
      gastrointestinal hemorrhage secondary to peptic ulcer disease. In each case,
      hepatic coma responded promptly to cathartics, enemas, and lactulose once
      bleeding ceased.

PMID- 11586462
TI  - Regarding "Subclavian arterial injury associated with blunt trauma" (Vascular
      Surgery 35:43-50, 2001).

PMID- 11586463
TI  - History, heterogeneity, developmental biology, and functions of quiescent hepatic
      stellate cells.
AB  - In 1876, von Kupffer described liver Sternzellen (star-shaped cells). The
      functions of these cells remained enigmatic for 75 years until Ito observed lipid
      containing perisinusoidal cells in human liver. In 1971, Wake demonstrated that
      the Sternzellen of von Kupffer and the fat-storing cells described by Ito were
      identical. Wake also established that these cells were important sites of vitamin
      A storage. Soon thereafter, Kent and Popper demonstrated that the stellate cells
      were intimately linked to the pathogenesis of hepatic fibrosis. Since then, these
      cells have been studied in detail. Quiescent stellate cells represent 5-8% of the
      total number of liver cells. They play a cardinal role in storage and controlled
      release of retinoids. They control extracellular matrix (ECM) turnover in the
      space of Disse by secreting the correct amounts of a limited number of ECM
      molecules, and by releasing matrix metalloproteinases and their inhibitors. By
      virtue of their long cytoplasmic processes, quiescent stellate cells presumably
      contribute to the control of blood flow through the sinusoidal capillaries. They
      are important sources of paracrine, autocrine, juxtacrine, and chemoattractant
      factors that maintain homeostasis in the microenvironment of the hepatic
      sinusoid.

PMID- 11586464
TI  - Hepatic blood flow regulation by stellate cells in normal and injured liver.
AB  - Hepatic stellate cells have received considerable attention as key components of
      the fibrogenic response to injury. Beyond this feature, they also have been
      implicated as regulators of sinusoidal vascular tone, and in disease states, in
      the pathogenesis of intrahepatic portal hypertension. The basis for this latter
      concept is derived from the following: (a) stellate cells are situated in a
      perisinusoidal orientation within the sinusoid, optimized for sinusoidal
      constriction; (b) a series of studies performed over the past decade have
      demonstrated that perisinusoidal stellate cells exhibit a remarkable capacity for
      cellular contraction, a characteristic that is most prominent after liver injury
      and stellate cell activation; and (c) in vivo microscopy studies have revealed
      that stellate cells can mediate sinusoidal constriction. Available evidence
      indicates that liver injury leads to a vascular disorder in which endothelin-1 is
      overproduced by stellate cells and endothelial cell-derived nitric oxide
      production is reduced. These abnormalities, in the context of exaggerated
      stellate cell contractility after liver injury, set up a paradigm in which
      stellate cells contribute to the increased intrahepatic resistance typical of
      portal hypertension. Furthermore, because stellate cell contractility and the
      mediators that control this function are dynamic processes, strategies that
      target exaggerated contractility provide an opportunity for novel therapeutics in
      intrahepatic portal hypertension.

PMID- 11586465
TI  - Matrix as a modulator of hepatic fibrogenesis.
AB  - The extracellular matrix (ECM) provides cells with positional information and a
      mechanical scaffold for adhesion and migration. It consists of collagens,
      glycoproteins, proteoglycans, glycosaminoglycans and molecules that are bound
      specifically by the ECM, such as certain growth factors/cytokines, matrix
      metalloproteinases (MMPs) and processing enzymes such as tissue transglutaminase
      and procollagen propeptidases. This finely tuned ecosystem is dysbalanced in
      chronic fibrogenesis, which can be regarded as a continuous wound-healing process
      and which results in scar formation. Importantly, the ECM directs cellular
      differentiation, migration, proliferation, and fibrogenic activation or
      deactivation. Partially via defined oligopeptide sequences or structural domains,
      the ECM transfers specific signals to cells that act in concert with growth
      factors/cytokines. These signals either confer stress activation, with a
      resultant fibrogenic response, or stress relaxation, with a fibrolytic response.
      Alternatively, ECM-derived peptides can modulate angiogenesis, or growth factor
      and MMP availability and activity. Current ECM-related antifibrotic strategies
      are based on the identification and in vivo application of ECM-derived
      biomodulatory peptides, peptide sequences, or their nonpeptidic mimetics. The
      latter open the opportunity of oral application and an extended biological half
      life. Examples are peptides derived from collagens VI (stress activation) and XIV
      (stress relaxation), or collagenous consensus peptides that remove ECM-bound MMPs
      and growth factors. Furthermore, certain peptides can be used as targeting
      structures to the fibrogenic lesion.

PMID- 11586466
TI  - Extracellular matrix degradation and the role of hepatic stellate cells.
AB  - Following liver injury, hepatic stellate cells (HSCs) become activated and
      express a combination of matrix metalloproteinases (MMPs) and their specific
      tissue inhibitors (TIMPs). In the early phases of liver injury (and primary cell
      culture), HSCs transiently express MMP-3, MMP-13, and uroplasminogen activator
      (uPA) and exhibit a matrix-degrading phenotype. In the later stages of liver
      injury and HSC activation, the pattern changes and the cells express a
      combination of MMPs that have the ability to degrade normal liver matrix, while
      inhibiting degradation of the fibrillar collagens that accumulate in liver
      fibrosis. This pattern is characterized by the combination of pro-MMP-2 and
      membrane type 1 (MT1)-MMP expression, which drive pericellular generation of
      active MMP-2 and local degradation of normal liver matrix. In addition there is a
      marked increase in expression of TIMP-1 leading to a more global inhibition of
      degradation of fibrillar liver collagens by interstitial collagenases (MMP-1/MMP
      13). These pathways play a significant role in the progression of liver fibrosis.
      Following cessation of liver injury, the pattern reverses and TIMP-1 in
      particular is rapidly downregulated. This phase is characterized by increasing
      activity of collagenases, degradation of liver matrix, and regression of liver
      fibrosis.

PMID- 11586467
TI  - Transcriptional regulation in hepatic stellate cells.
AB  - Modulation of gene expression through altered transcription regulates stellate
      cell behavior in normal liver and following hepatic injury. Transcription factors
      are generally classified according to conserved motifs within either the
      activation- or DNA- binding domains of the molecules. Transcriptional activity in
      stellate cells represents a delicate fine tuning of multiple inputs. Activities
      of these transcription factors are modified by their intracellular localization,
      rate and pathway of degradation, oligomerization, and interactions with
      heterologous factors and chromatin, as well as by posttranslational
      modifications, including phosphorylation, glycosylation, and acetylation. General
      paradigms of transcriptional control are increasingly being validated in hepatic
      stellate cells, particularly involving the transcription factors CCAAT/enhancer
      binding proteins, c-myb, CREB, nuclear factor kappaB, peroxisome proliferator
      activated receptor, and Kruppel-like zinc finger factors. Although there are no
      simple rules that govern mechanisms of transcriptional regulation in stellate
      cells, continued advances will yield new insights into their role in normal liver
      homeostasis and in the response to injury.

PMID- 11586468
TI  - Cytokine receptors and signaling in hepatic stellate cells.
AB  - Following acute or chronic liver tissue damage, hepatic stellate cells (HSCs)
      undergo a process of activation toward a phenotype characterized by increased
      proliferation, motility, contractility, and synthesis of extracellular matrix
      components. Activation of HSCs is regulated by several soluble factors, including
      growth factors, cytokines, chemokines, and products of oxidative stress, as well
      as by extensive changes in the composition and organization of the ECM. Different
      groups of soluble factors may be classified according to their prevalent
      biological effect: (a) factors promoting HSC proliferation and/or migration
      (i.e., platelet-derived growth factor, basic fibroblast growth factor, insulin
      like growth factor-1); (b) factors promoting fibrillar ECM accumulation,
      particularly transforming growth factor-beta1; (c) factors with a prevalent
      contractile effect on HSCs, such as endothelin-1, thrombin, angiotensin-II and
      vasopressin, although all these agents also may promote HSC proliferation; (d)
      proinflammatory cytokines and chemokines; and (e) cytokines with a prominent
      antiinflammatory/antifibrogenic activity, such as interleukin-10 and interferon
      gamma. Additional important issues are represented by the relationship between
      cytokine and integrin signaling, and by the effects of oxidative stress-related
      molecules on cytokine signaling. In the past decade the major intracellular
      signaling pathways elicited by these factors in HSCs have been greatly
      elucidated.

PMID- 11586469
TI  - Interactions between hepatic stellate cells and the immune system.
AB  - Stellate cells and immune cells are both active participants in the pathogenesis
      of liver disease. Interactions between these two populations are important
      determinants of disease outcome. Kupffer cells, neutrophils, and lymphocytes all
      have the potential to influence stellate cells. They produce a host of humoral
      mediators, including oxidants, nitric oxide, cytokines, eicosanoids, and
      proteinases, which can affect stellate cell proliferation, gene expression, and
      contractility. One important feature of stellate cell-immune cell interactions is
      that they are bidirectional. Not only do stellate cells receive signals from
      leukocytes, but they also elaborate signals that target leukocytes. Specifically,
      stellate cells can promote leukocyte chemotaxis and adherence, and they may also
      influence leukocyte activation by producing regulatory cytokines. Studies in
      culture provide an important background for understanding the effects of specific
      mediators on stellate cells and immune cells. Experiments in vivo offer an
      important adjunct, but often lead to confounding effects that limit
      interpretation. Both types of studies are required to develop a better
      understanding of the complex interplay between stellate cells and leukocytes.

PMID- 11586470
TI  - Hepatic stellate cell behavior during resolution of liver injury.
AB  - Acute self-limiting and chronic liver injury are both associated with activation
      and proliferation of hepatic stellate cells (HSCs). In chronic injury, activated
      stellate cells are the major source of the collagens that comprise fibrosis and
      cirrhosis, as well as of the tissue inhibitors of metalloproteinases (TIMPs)
      which inhibit collagen degradation. Recovery from acute and chronic injury is
      characterized by apoptosis of activated HSCs, which removes extracellular matrix
      producing cells that are also expressing TIMPs, thereby relieving the inhibition
      of matrix degradation. HSC apoptosis is regulated in progressive injury and
      counterbalances cell proliferation. Apoptosis probably also represents a default
      pathway for the HSCs. The survival of activated HSCs in liver injury is dependent
      on soluble growth factors and cytokines, and on components of the fibrotic
      matrix. Additionally, stimulation of death receptors expressed on HSCs can
      precipitate their apoptosis. Our increasing understanding of the process of
      stellate cell behavior in recovery from injury is likely to be important to the
      design of antifibrotic therapies.

PMID- 11586471
TI  - Hepatic stellate cells as a target for the treatment of liver fibrosis.
AB  - Following chronic liver injury of any etiology, there is progressive fibrosis. To
      date, removing the causative agent is the only effective therapy to stop or even
      reverse liver fibrosis. Therefore, the development of effective antifibrotic
      therapies represents a challenge for modern hepatology. In the past decade,
      dramatic advances have been made in the understanding of the cellular and
      molecular mechanisms underlying liver fibrogenesis. The identification of
      activated hepatic stellate cells (HSCs) as the major fibrogenic cell type in the
      injured liver, as well as the recognition of key cytokines involved in this
      process, have facilitated the design of promising new antifibrotic therapies.
      These therapies are aimed at inhibiting the accumulation of activated HSCs at the
      sites of liver injury and preventing the deposition of extracellular matrix.
      Although many of these approaches are effective in experimental models of liver
      fibrosis, their efficacy and safety in humans are still unknown. This review
      describes the current therapeutic approaches for liver fibrosis and discusses
      different features of activated HSCs as a target to design new treatments to
      inhibit scar formation in chronic liver diseases.

PMID- 11586472
TI  - A 35-year-old woman with progesterone implant contraception and multiple liver
      masses.

PMID- 11586473
TI  - Come in from the cold.

PMID- 11586474
TI  - Patient temperature: an introduction to the clinical guideline for the prevention
      of unplanned perioperative hypothermia.

PMID- 11586476
TI  - A profile of perianesthesia nursing patient outcome research, 1994-1999.
AB  - The purpose of this research was to profile the current body of perianesthesia
      nursing research and extend the findings of previous integrative reviews
      completed on research from 1982 to 1993. The tables of contents from 18 nursing
      journals were examined and 31 studies met inclusion criteria. Findings indicated
      that some improvements were made by perianesthesia nurse researchers in using the
      scientific method. No studies replicated previously published research before
      1994. Pediatric and elderly studies were scarce. Free-standing ambulatory surgery
      continues to be an under-represented research setting.

PMID- 11586477
TI  - CAMPing in the PACU: using complementary and alternative medical practices in the
      PACU.
AB  - This case study will show the effectiveness of various forms of holistic healing
      (Therapeutic Touch, Healing Touch, Reiki, and reflexology) when used during the
      perianesthesia period for reduction of stress and pain. Brief introductions of
      each of the forms of complementary medicine will be provided with correlation to
      the case study. The reader will see how the nurse interprets the physical and
      emotional changes of the patient and identifies how and when to intercede with
      complementary forms of healing.

PMID- 11586478
TI  - Perianesthesia legacy: one nurse at a time.

PMID- 11586479
TI  - Celebrating successes through poster presentation.

PMID- 11586480
TI  - A day to remember.

PMID- 11586481
TI  - Biochemical effects of dietary intakes of different broccoli samples. I.
      Differential modulation of cytochrome P-450 activities in rat liver, kidney, and
      colon.
AB  - Modulation of xenobiotic metabolism, including cytochrome P-450 (CYP) enzyme
      activities, due to dietary intakes of cruciferous vegetables, has been described
      in animals and humans, and the induction of CYP1A enzymes is suggested mainly to
      be related to the content of indolyl glucosinolates in these vegetables. The aim
      of the present study was to evaluate the effects on specific CYP activities of
      various broccoli samples containing different levels of glucosinolates. Groups of
      rats were fed 1 of 8 broccoli samples from 2 cultivars grown at different
      conditions. Thirteen different glucosinolates were quantified. The content of the
      4 major glucosinolates, glucoraphanin (GRAP), glucoiberin, glucobrassicin (GB),
      and neoglucobrassicin (NeoGB) varied 5.6-, 2.7-, 3.2-, and 6.6-fold,
      respectively, among the broccoli samples. Dietary broccoli induced the CYP1A
      enzyme activities, 7-ethoxyresorufin-O-deethylase (EROD) and 7-methoxyresorufin-O
      demethylase (MROD), in rat liver, weakly in colon, but not in kidney. In
      concordance, the hepatic metabolism of 2-amino-1-methyl-6-phenylimidazo(4,5
      b)pyridine (PhIP) to the proximate carcinogen N-OH-PhIP, a CYP1A-related
      activity, was enhanced by broccoli. The 7-pentoxyresorufin-O-depenthylase (PROD)
      activity, an assay for CYP2B1/2, was weakly induced in colon and kidney but not
      in liver by broccoli. The 2 beta-OH- and 6 beta-OH-testosterone hydroxylase
      activities were induced in liver microsomes, showing that broccoli increased
      CYP3A activity. The observed modulations of CYP activities depended clearly on
      the broccoli sample used, and significantly different responses were observed for
      different cultivars and growth conditions. These results indicate that modulation
      of CYP metabolism by broccoli may vary significantly in humans as well, as the
      content of glucosinolates and other active substances also varies between
      commercially available broccoli samples. The different effects depending on the
      vegetable sample eaten have to be considered in future experiments and dietary
      recommendations.

PMID- 11586482
TI  - Biochemical effects of dietary intake of different broccoli samples. II.
      Multivariate analysis of contributions of specific glucosinolates in modulating
      cytochrome P-450 and antioxidant defense enzyme activities.
AB  - Dietary broccoli exposure modulates various cytochrome P-450 (CYP)-associated
      activities and antioxidant defense enzyme activities in liver, colon, and kidney
      of rats. We present an analysis by the partial least-square method (PLS) of the
      contribution of single glucosinolates in modulating xenobiotic metabolizing and
      antioxidant defense enzyme activities. Generally, modulation of colonic enzyme
      activities was well described (58% to 75%) by models consisting of 3 principal
      components (PCs). The indolyl glucosinolates were not the only major contributors
      to the regulation of colonic 7-ethoxyresorufin O-deethylase (EROD) and 7
      methoxyresorufin O-demethylase (MROD) activities, as would be expected from
      results of previous experiments testing the pure compounds, glucobrassicin (GB),
      neoglucobrassicin (NeoGB), and 4-methoxyglucobrassicin (4-MeOGB). In hepatic and
      renal microsomes, the modulation of enzyme activities could be partly described
      for hepatic and renal 7-pentoxyresorufin O-deethylase (PROD) activities (42% to
      44%, 3 to 4 PCs), hepatic superoxide dismutase activity (45%, 2 PCs), and renal
      glutathione peroxidase (GSH Px) and glutathione reductase (GSSG Red) activities
      (43%, 3 PCs). These results indicate that substances other than glucosinolates in
      the complex mixtures modulate hepatic EROD, MROD, GSH Px, and GSSG Red activities
      or that the active glucosinolate metabolites vary in their systemic disposition.

PMID- 11586483
TI  - Effect of exercise training on serum leptin levels in type 2 diabetic patients.
AB  - To evaluate the effect of exercise training on serum leptin levels 50 sedentary
      subjects with type 2 diabetes were enrolled in either 6 weeks of aerobic exercise
      training with diet therapy (n = 23) or diet therapy alone (n = 27). The training
      program consisted of walking and cycle ergometer exercise for 1 hour at least 5
      times per week, with the intensity of exercise maintained at 50% of maximum
      oxygen uptake. Serum leptin levels decreased significantly in the exercise
      training (TR) group (7.2 +/- 3.6 to 4.6 +/- 2.5 ng/mL, P <.05), but not in the
      sedentary (SED) group (6.9 +/- 3.4 to 5.6 +/- 2.9 ng/mL). Leptin levels
      standardized for percentage body fat (dividing serum leptin level by percentage
      body fat) after treatment were lower in the TR subjects compared with the SED
      subjects. Body weight and percentage body fat decreased in all patients; however,
      no significant changes were observed in either group. Fasting concentrations of
      plasma insulin and cortisol and the urinary excretion of 17-hydroxycorticosteroid
      (17-OHCS) did not differ between the groups either before or after treatment.
      Fasting plasma glucose and hemoglobin A(1c) (HbA(1c)) improved significantly in
      both groups, although no significant differences were observed between the groups
      either before or after treatment. Ventilatory threshold increased significantly
      in the exercise training subjects. This study demonstrates that exercise training
      in type 2 diabetic subjects reduces serum leptin levels independent of changes in
      body fat mass, insulin, or glucocorticoids.

PMID- 11586484
TI  - Serum leptin in formerly small-for-gestational-age children during adolescence:
      relationship to gender, puberty, body composition, insulin sensitivity,
      creatinine, and serum uric acid.
AB  - Serum leptin levels reflect body fat mass (FM), and have been described to be
      related to serum uric acid levels in adult type 2 diabetic and healthy subjects.
      We therefore aimed to evaluate the interrelationship between leptin and markers
      of the metabolic syndrome by studying serum leptin concentration, body mass index
      (BMI), percent body fat (Fat%), total fat mass (FM), sum of skinfolds (SS),
      triglycerides (TG), total cholesterol (CHOL), high-density lipoprotein
      cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose,
      insulin, calculated insulin resistance (HOMA), creatinine (CR), and uric acid
      (UA) concentration in 50 former small-for-gestational-age (SGA) children and 21
      infants born adequate for gestational age (AGA) at the time of mid-puberty. Our
      data confirm previous results showing a positive association between leptin and
      body fatness, and female gender. Twelve children with impaired glucose tolerance
      (IGT) had higher UA levels than subjects with normal glucose tolerance (NGT) (5.1
      +/- 1.1 v 4.2 +/- 1.2 mg/dL, P <.05), and showed the strongest relation between
      serum leptin and UA (r =.76, P <.001). Multiple regression analyses demonstrated
      that gender, estimates of total body adiposity (Fat% and SS), birth weight (BW),
      gestational age (GA), stimulated glucose and insulin, and serum UA are
      independently associated with serum leptin concentration in former SGA children
      with dysglycemia (R(2) =.89, P <.001). A long-term effect of intrauterine growth
      restriction on body fatness, metabolic syndrome, and serum leptin levels is
      suggested.

PMID- 11586485
TI  - Serum magnesium status during lipid-lowering drug treatment in non-insulin
      dependent diabetic patients.
AB  - Serum magnesium concentration (S-Mg) has been reported to be inversely associated
      with atherogenic lipid fractions and with blood glucose concentrations. In some
      studies on humans, oral magnesium supplementation has been found to improve the
      lipoprotein balance. Against this background the present study was undertaken to
      determine whether reductions in atherogenic lipid fractions are associated with S
      Mg alterations. Total S-Mg was measured in 23 patients with non-insulin-dependent
      diabetes mellitus (NIDDM) treated with the lipid-lowering drugs gemfibrozil and
      simvastatin in a double-blind cross-over study. The mean S-Mg at the end of the
      initial placebo period, ie, before active treatment, was 0.80 (SD 0.06) mmol/L.
      Treatment with gemfibrozil 600 mg twice daily for 4 months decreased S-Mg by 0.02
      mmol/L (P =.02), and treatment with simvastatin 10 mg daily for 4 months again
      decreased S-Mg by 0.02 mmol/L (P =.10; not significant [NS]) The changes in S-Mg
      during the 2 different treatment periods were closely correlated (r = 0.66, P
      <.001). Fasting plasma glucose concentrations increased significantly by 17%
      during both drug regimens. The changes in fasting plasma glucose and S-Mg were
      significantly correlated both during gemfibrozil treatment (r = -0.56, P <.01)
      and during treatment with simvastatin (r = -0.44, P <.05). Changes in glucose
      tolerance or insulin sensitivity did not correlate to changes in S-Mg. The
      associations between changes in serum very-low-density lipoprotein (VLDL)
      fractions and S-Mg did not reach statistical significance (r = -0.37, P <.10).
      Changes in low-density lipoprotein (LDL) cholesterol and S-Mg did not correlate.
      In conclusion, total S-Mg concentration decreased during treatment with
      gemfibrozil and simvastatin in patients with NIDDM. During both drug regimens
      changes in S-Mg status were inversely correlated to changes in plasma glucose
      concentrations, while changes in lipid status were not significantly correlated
      with changes in S-Mg.

PMID- 11586486
TI  - Polymorphisms 1704G/T and 2184A/G in the RAGE gene are associated with
      antioxidant status.
AB  - The formation of advanced glycation end products (AGEs) and oxidative stress are
      supposed to play an important role in the development of diabetic late
      complications. AGEs can bind to several binding sites including receptor of
      advanced glycation end products (RAGE). AGE-RAGE interaction results in free
      radical generation. The aim of the present study was to investigate the impact of
      previously described polymorphisms in the RAGE gene (G82S, 1704G/T, 2184A/G, and
      2245G/A) on the glycoxidation status in non-insulin-dependent diabetes mellitus
      (NIDDM). A total of 371 unrelated caucasian subjects were enrolled in the study.
      The NIDDM group consisted of 202 subjects, and the presence of late diabetic
      complications in 5 particular localizations was expressed as an index (I(compl)).
      The nondiabetic group included 169 subjects. Glycated hemoglobin (HbA(1c)),
      glycated stratum corneum proteins (Amadori, AGE), total carotenoids, alpha- and
      beta -carotene, gamma-tocopherol, lutein, lycopene, and alpha-tocopherol were
      measured in each subject. Statistically significant differences in allele
      frequencies between the NIDDM and the nondiabetic groups were observed for the
      G82S and 2245G/A polymorphisms (P =.047 and .032, respectively). HbA(1c),
      Amadori, and AGE did not reveal any significant association with any of the
      polymorphisms analyzed. However, significant differences between subjects bearing
      "wild-type majority" genotypes 1704GG+2184AA and subjects with "mutated"
      genotypes were found for total carotenoids (P =.001), alpha-carotene (P =.046),
      beta-carotene (P =.028), lutein (P =.001), lycopene (P =.006), and alpha
      tocopherol (P =.047). I(compl) significantly correlated with the plasma levels of
      all antioxidants (all P <.01), while no correlation of I(compl) with glycation
      variables was observed. The newly identified intron polymorphisms in the RAGE
      gene were proved to be associated with the antioxidant status in NIDDM subjects.
      The extent of diabetic vascular disease is related to the plasma levels of
      antioxidants.

PMID- 11586487
TI  - Exposure to an obesity-inducing diet early affects the pattern of expression of
      peroxisome proliferator, retinoic acid, and triiodothyronine nuclear receptors in
      the rat.
AB  - Since evidence has appeared that alpha and gamma isoforms of the peroxisome
      proliferator receptors (PPARs) are involved in the regulation of triglyceride
      homeostasis and in the control of the differentiation of adipocytes that is
      required for the development of obesity, a large number of studies have
      investigated the physiologic role of nuclear receptors in the control of energy
      balance. The aim of this study was to determine the early effects of an obesity
      inducing diet on the expression of PPAR alpha and gamma and other nuclear
      receptors such as all-trans retinoic acid receptor (RAR) and triiodothyronine
      receptor (TR), which all form functional heterodimers with a common partner, the
      9-cis retinoic acid receptor (RXR). The experiment used a cafeteria diet where
      60% of the energy was supplied as lipids. This diet was offered to young rats for
      8 and 28 days and the expression of nuclear receptors was determined at the end
      of each experimental time period (1) in the liver by assaying the binding
      properties of RAR and TR and by quantifying mRNA levels of RAR beta, TR
      alpha(1)beta(1), RXR alpha, and PPAR alpha, and (2) in the white adipose tissue
      (WAT) by quantifying mRNA levels of RAR alpha, RXR alpha, TR alpha(1)beta(1), and
      PPAR gamma(2). After 8 days of cafeteria diet a significant decrease of RAR and
      TR maximal binding capacity (MBC) was observed in the liver (-20.1% and -35.0%,
      respectively, P <.05) and the level of the mRNA of RAR beta was significantly
      decreased (-17.4%, P <.05). After 28 days of cafeteria diet, the level of the
      mRNA of PPAR alpha and acyl-CoA oxidase (ACOX) was significantly increased
      (+54.5% and +37.8%, P <.01 and P <.05, respectively), whereas the MBC of RAR and
      TR was significantly decreased (-16.0% and -23.4%, P <.01), as were the mRNA
      levels of RAR beta and TR alpha(1) beta(1) (-28.5% and -32.0%, P <.05). The level
      of RXR alpha mRNA was unchanged. In WAT, the mRNA level of PPAR gamma(2) was
      significantly increased after 28 days of cafeteria diet (+49.5%, P <.05) and the
      mRNA levels of RAR alpha and TR alpha(1) beta(1) significantly decreased (-22.3%
      and -31.0%, P <.05). These results as a whole showed that a high-fat diet can
      induce early modifications in the pattern of expression of nuclear receptors in
      the liver and the WAT. These modifications could be compatible with an early
      adaptive phenomenon. Further investigations are necessary to better understanding
      the link between the modifications of the pattern of expression of these
      receptors and plasticity of adipose tissue leading to the onset of obesity.

PMID- 11586488
TI  - Tissue contents and subcellular distribution of chromium and other trace metals
      in experimental diabetic rats after intravenous injection of Cr 50-enriched
      stable isotopic tracer solution.
AB  - In order to study the metabolism of essential trace elements in diabetics, we
      studied alloxan-diabetic rats for the distribution patterns of chromium (Cr),
      cobalt (Co), iron (Fe), selenium (Se), and zinc (Zn) in the liver, kidney,
      pancreas, and testes, as well as in the organ subcellular fractions. Normal rats
      were used as controls. Cr 50-enriched stable isotopic tracer solution was given
      by intravenous injection to avoid the difficulties of estimation of Cr status.
      Our data show that the concentrations of Zn in liver and kidney, of Co, Fe, and
      Zn in pancreas, and of Fe and Zn in testes of the diabetic rats were
      significantly higher than in the control rats. Nevertheless, the concentrations
      of Cr in pancreas, Fe in kidney, and Cr and Se in testes of the diabetic rats
      were significantly lower than in the controls. Furthermore, we observed
      significant alterations of element concentrations in subcellular fractions of
      various organs in the diabetic rats. These results suggest that changing hormone
      levels may interfere with the accumulation of some trace elements both in the
      organs and in the subcellular fractions of rats.

PMID- 11586489
TI  - Glucose disposal rates calculated from 60- to 90-minute isoglycemic
      hyperinsulinemic glucose clamp correlate with cardiovascular risk factors in
      borderline hypertensive young men.
AB  - The hyperinsulinemic glucose clamp is generally performed for at least 120
      minutes, due to assumptions of steady-state. We were interested in relationships
      between glucose disposal rate (GDR) and cardiovascular risk factors, rather than
      a standard measure of insulin sensitivity per se. Therefore, we analyzed 120
      minute clamps performed on borderline hypertensive, but otherwise healthy young
      men (n = 19). GDR was calculated at different time points and related to baseline
      cardiovascular risk factors and responses to a mental stress test (MST). The 60-,
      90-, and 120-minute GDR correlated significantly with serum high-density
      lipoprotein (HDL) cholesterol (r=.59, r=.50, and r=.53, respectively), heart rate
      (HR) during MST (r = -.65, r = -.64, and r = -.58, respectively) and plasma
      epinephrine (Epi) (r = -.55, r= -.58, and r = -.56, respectively) and
      norepinephrine (NE) (r = -.52, r = -.49, and r = -.48, respectively) 1 minute
      after announcement of the MST (all P <.05). Although not statistically
      significant at all time points, similar relationships were observed between GDR
      and resting HR, systolic blood pressure (BP) at rest and during mental stress,
      body mass index (BMI), serum total cholesterol (Chol), serum triglycerides (TG),
      and blood hemoglobin (HgB), with remarkable consistency from about 40 to 50
      minutes onwards. HDL cholesterol and Epi remained independent in stepwise
      multiple regression analyses with the 60-, 90-, and 120-minute GDR as dependent
      variables (all P <.05). We suggest that 60- to 90-minute glucose clamps may
      provide information about the relationship between insulin sensitivity and
      various cardiovascular risk factors in borderline hypertensive young caucasian
      men.

PMID- 11586490
TI  - Paradoxical weight loss with extra energy expenditure at brown adipose tissue in
      adolescent patients with Duchenne muscular dystrophy.
AB  - We examined the energy expenditure in patients with Duchenne muscular
      dystrophy(DMD) to evaluate the cause of the paradoxical weight loss observed in
      large numbers of adolescent patients before any obvious impairment of their
      swallowing function. In the morning, resting energy expenditure (REE)/m(2) was
      almost the same as that in normal controls despite a reduction in fat-free mass
      (FFM); thus, REE/m(2)/FFM was significantly increased in patients (median, 21.2
      kcal/m(2)/FFM kg; range, 17.7 to 44.2, P =.012). A thermographic examination in
      the morning showed an obvious elevation of the body surface temperature on the
      back. This phenomenon was consistent with a paradoxical fall in the low frequency
      (LF)/high frequency (HF) ratio at night analyzed using the inter-RR spectrum by
      24-hour electrocardiogram, which indicated relative activation of the sympathetic
      nervous system. The urinary secretion of norepinephrine at night was also
      significantly greater in patients (median, 0.119 microg/kg/h; range, 0.061 to
      0.219, P =.011). These results suggest that paradoxical activation of the
      sympathetic nervous system may accelerate the production of heat in brown adipose
      tissue (BAT) and increase the level of energy consumption in patients, and that
      adolescent DMD patients may require greater caloric intake than expected to
      maintain body weight, which is important to improve the prognosis of their
      respiratory function.

PMID- 11586491
TI  - Is the association between dietary fat intake and insulin resistance modified by
      physical activity?
AB  - The rising prevalence of type 2 diabetes, a condition associated with insulin
      resistance, is commonly attributed to changes in dietary patterns and physical
      activity levels in susceptible populations. However, few studies have described
      the independent effects of dietary intake and physical activity on the degree of
      insulin sensitivity within populations or examined the possibility of
      interactions between dietary factors and physical activity. This study was
      undertaken to describe the relationship between the quantity and pattern of
      dietary fat intake on fasting insulin levels (a marker of insulin sensitivity)
      and to investigate whether the association was modified by physical activity. A
      cross-sectional study of 815 nondiabetic men and women (30 to 71 years) recruited
      from a population-based sampling frame was undertaken. Diet was characterized
      using a semiquantitative food frequency questionnaire. Physical activity level
      (PAL), the ratio of total energy expenditure to basal metabolic rate, was
      estimated using individually calibrated heart rate monitoring, a method
      previously shown to be an objective and valid method for assessing total energy
      expenditure. In a linear regression model adjusted for total energy intake, total
      fat intake bordered on a significant association with fasting insulin (b =
      0.000081; P =.058), and the polyunsaturated to saturated fat ratio (P:S ratio) of
      the diet was negatively associated with fasting insulin concentration (b = -0.37,
      P <.001). A negative association was observed between the PAL and fasting insulin
      (b = -0.12, P =.025). The association of the P:S ratio and PAL with fasting
      insulin remained significant when adjusted for each other and for total fat,
      total energy intake, body mass index (BMI), waist-to-hip ratio (WHR), age, sex,
      family history of diabetes, smoking status, and alcohol intake (P:S ratio, b = 
      0.24, P =.003; PAL, b = -0.13; P =.007). The association with total fat intake
      was no longer significant in this multivariate model (b = 6.7 x 10(-6); P =.858).
      There was no evidence for an interaction between total dietary fat intake and PAL
      (b = -0.000048; P =.243) or between the P:S ratio and PAL (b = -0.013; P =.949).
      These data demonstrate an independent association between the P:S ratio of the
      diet, the overall level of physical activity, and the fasting insulin
      concentration, a marker of insulin sensitivity. There was no evidence that the
      association between dietary fat intake and insulin resistance was modified by
      physical activity. The findings provide further support for efforts to promote
      increases in overall physical activity and modifications in the pattern of
      dietary fat intake in the whole population.

PMID- 11586492
TI  - Pioglitazone reduces urinary podocyte excretion in type 2 diabetes patients with
      microalbuminuria.
AB  - In various renal diseases, including diabetic nephropathy, detection of podocytes
      in the urine indicates severe injury to podocytes in the glomeruli. Pioglitazone
      is a newly developed antidiabetic agent that attenuates insulin resistance. The
      aim of the present study was to determine whether pioglitazone affects urinary
      albumin excretion (UAE) or the number of urinary podocytes or both in type 2
      diabetes patients with microalbuminuria. Twenty-eight patients with normotensive
      type 2 diabetes and microalbuminuria (18 men and 10 women; mean age, 52.5 years)
      and 30 age-matched normotensive controls (20 men and 10 women; mean age, 51.5
      years) were included in the study. Urinary podocytes were detected by
      immunofluorescence with a monoclonal antibody against podocalyxin. Patients were
      randomly assigned to 2 groups: a pioglitazone-treatment group (30 mg/day, n = 14)
      and a placebo group (n = 14). Treatment was continued for 6 months. Podocytes
      were absent in the urine of healthy controls, but detected in 17 of 28 diabetic
      patients (60.7%). UAE was reduced from 96.7 +/- 50.5 microg/min to 39.7 +/- 22.9
      microg/min (P <.01) in the pioglitazone-treatment group, and the number of
      urinary podocytes was reduced from 0.9 +/- 1.0 cells/mL to 0.1 +/- 0.2 cells/mL
      (P <.001). Neither UAE nor the number of urinary podocytes was affected in the
      placebo group. These data indicate that pioglitazone is effective for reducing
      UAE and podocyte injury in early-stage diabetic nephropathy.

PMID- 11586493
TI  - Altered lipid profile, leptin, insulin, and anthropometry in offspring of South
      Asian immigrants in the United States.
AB  - South Asians who immigrate to the United States have a propensity toward insulin
      resistance, central obesity, and elevated total cholesterol:high-density
      lipoprotein (HDL) ratio. To evaluate whether these alterations are apparent at a
      younger age, we studied 32 offspring of South Asian immigrants and compared them
      with 29 of European descent between 18 to 30 years of age. American-born South
      Asian males had significantly higher total cholesterol, low-density lipoprotein
      (TC:LDL) ratios, triglycerides, and fasting insulin levels (13.9 +/- 7.1 and 10.0
      +/- 5.5 microU/mL, P <.01) than their European counterparts. The South Asian
      females only had increased plasma insulin levels (15.3 +/- 8.8 and 10.0 +/- 5.1
      microU/mL, P =.05). The entire South Asian group had higher truncal skinfold
      thickness (40.1 +/- 18.1 and 30.3 +/- 12.6 mm, P = <.05) and lower insulin-like
      growth factor binding protein (IGFBP)-1 levels (46.8 +/- 33.4 and 56.0 +/- 33.4
      microg/L, P =.05). Plasma leptin levels were also significantly higher in both
      males (4.3 +/- 2.5 v 2.8 +/- 1.3 ng/mL, P =.0001) and females (20.5 +/- 10.3 v
      10.3 +/- 6.3 ng/mL, P =.002) South Asian subjects. A significant correlation
      between plasma leptin and insulin, triglycerides, TC, and body mass index (BMI)
      was seen in the South Asian males. South Asians born in the United States show
      evidence for an altered metabolic profile in young adulthood. The relative
      contributions of inheritance and nutritional practices early in life to this
      alteration remain unclear.

PMID- 11586494
TI  - Clinical features of familial gout and effects of probable genetic association
      between gout and its related disorders.
AB  - We examined whether the age at onset, gender, arthritic manifestations, and
      tophus formation in familial gout are different from those in nonfamilial gout,
      and we also examined the contributory effect of genetic association to the
      concurrence of hypertriglyceridemia, hypercholesterolemia, type 2 diabetes
      mellitus (DM), hypertension, obesity, and renal insufficiency with gout in
      Taiwan. A total of 21,373 gout patients' data from Ho-Ping Gout database were
      analyzed in this study retrospectively. The clinical and laboratory data were
      compared between familial and nonfamilial gout. Mean age at onset of gout in
      familial subjects was significantly 7.5 years lower than that of nonfamilial
      subjects (40.9 +/- 13.4 v 48.4 +/- 14.2 years, P =.0001), while gender, arthritic
      severity, and tophus formation were not significantly different between these 2
      groups. Familial gout had lower serum triglyceride (TG), total cholesterol (TC),
      and percentage of hypertension than nonfamilial gout (182.4 +/- 125.3 v 195.9 +/-
      135.8 mg/dL, P =.0001; 207.5 +/- 42.5 v 210.4 +/- 48.8 mg/dL, P =.0003; and
      19.57% v 22.56%, P <.0001, respectively). Their serum creatinine, body mass index
      (BMI), and percentage of type 2 DM were not significantly different. Our results
      demonstrate that familial gout is associated with precocious onset. Furthermore,
      the contributory effect of genetic association to the concurrence of
      hyperlipidemia and hypertension with gout is less than that of environmental
      factors, while the effect of genetic association to the concurrence of obesity,
      type 2 DM, and renal insufficiency with gout is equivalent to that of
      environmental factors.

PMID- 11586495
TI  - Glucose uptake and glycolytic flux in adipose tissue from rats adapted to a high
      protein, carbohydrate-free diet.
AB  - Rates of glucose uptake by epididymal and retroperitoneal adipose tissue in vivo,
      as well as rates of hexose uptake and glycolytic flux in isolated adipocytes,
      were determined in rats adapted to a high-protein, carbohydrate-free (HP) diet
      and in control rats fed a balanced (N) diet. Adaptation to the HP diet induced a
      significant reduction in rates of glucose uptake, estimated with 2-deoxy-[1-(3)H]
      glucose, both by adipose tissue (epididymal and retroperitoneal) in vivo and by
      isolated adipocytes. Twelve hours after replacement of the HP diet with the
      balanced diet, rates of adipose tissue uptake in vivo in HP-adapted rats returned
      to levels that did not differ significantly from those in N-fed rats. The rate of
      flux in the glycolytic pathway, estimated with (3)H[5]-glucose, was also
      significantly reduced in adipocytes from HP-fed rats. In agreement with the above
      findings, the activities of hexokinase (HK), phosphofructo-1-kinase (PFK-1), and
      pyruvate kinase (PK) were markedly reduced in adipose tissue from HP-adapted
      rats. The activity of pyruvate kinase was partially reverted by diet replacement
      for 12 hours. The low-plasma insulin and high-glucagon levels in HP-fed rats may
      have played an important role in the reduction of adipose tissue glucose
      utilization in these animals.

PMID- 11586496
TI  - Hypothalamic appetite-regulating neuropeptide mRNA levels in cachectic nude mice
      bearing human tumor cells.
AB  - We previously reported that the human melanoma cell line, SEKI, induces severe
      weight loss in nude mice. In the present study, we examined the expression of
      weight-regulating neuropeptide mRNAs in the hypothalamus of this cancer cachectic
      model by using a sensitive quantitative reverse transcriptase-polymerase chain
      reaction (RT-PCR) method and in situ hybridization. mRNA levels of neuropeptide Y
      (NPY) and corticotropin-releasing hormone (CRH) in the whole hypothalamus were
      elevated significantly in the SEKI mice as compared with control mice. In situ
      hybridization showed that NPY and CRH mRNA were upregulated in the arcuate
      nucleus and the paraventricular nucleus, respectively. There were no significant
      differences in melanin-concentrating hormone (MCH), orexin (OX), and
      cholecystokinin mRNA levels between the SEKI and control mice. These results
      suggest that the NPYergic system is functioning in the rodent model of cancer
      cachexia; however, the role of the CRHergic system in energy homeostasis remains
      to be elucidated. This is the first report of the hypothalamic neuropeptide
      response to cachexia-inducing human cells.

PMID- 11586497
TI  - Determinants of homocysteine during weight reduction in obese children and
      adolescents.
AB  - Plasma homocysteine levels have been shown to be associated with indexes of
      obesity and insulin resistance in obese children and adolescents. We, therefore,
      investigated the contribution of changes in body composition, markers of insulin
      resistance, folate, and vitamin B(12) to changes in homocysteine during a weight
      reduction program in obese children and adolescents. Thirty-seven obese white
      girls (mean SD; age, 12 +/- 1.8 years, body mass index [BMI], 26.9 +/- 5.25) and
      19 obese white boys (age, 11.9 +/- 1.7 years; BMI, 26.2 +/- 5.2) were
      investigated for body composition, fasting total plasma homocysteine (tHcy),
      insulin, C-peptide, folate, and vitamin B(12) before and after a 3-week weight
      reduction program including physical activities. During weight reduction BMI, fat
      mass (FM), percentage fat mass, insulin, and C-peptide decreased significantly,
      whereas homocysteine and vitamin B(12) showed a significant increase. Folate and
      lean body mass (LBM) remained unchanged. tHcy concentration before weight
      reduction was a function of age, folate, and C-peptide, whereas tHcy
      concentration after weight reduction was a function of folate and baseline LBM.
      Changes in tHcy during weight reduction correlated significantly with baseline
      LBM and were related inversely to changes in LBM during weight reduction.
      Children who increased LBM showed lower increases in tHcy compared with children
      who lost LBM. In multiple linear regression analysis, only baseline LBM
      contributed independently and significantly to changes in tHcy. Our study
      suggests that LBM has a significant impact on tHcy metabolism during weight
      reduction.

PMID- 11586498
TI  - Macrophage 3-hydroxy-3-methylglutaryl coenzyme a reductase activity in
      sitosterolemia: effects of increased cellular cholesterol and sitosterol
      concentrations.
AB  - Sitosterolemia is a rare, recessively inherited disease characterized clinically
      by accelerated atherosclerosis and xanthomas and biochemically by hyperabsorption
      and retention of sitosterol and other plant sterols in tissues. Decreased
      cholesterol biosynthesis and inhibition of 3-hydroxy-3-methylgluratyl coenzyme A
      (HMG-CoA) reductase and other enzymes in the biosynthetic pathway have been
      associated with enhanced low-density lipoprotein (LDL) receptor function. We
      examined the effects of cholesterol and sitosterol on sterol concentrations and
      composition and HMG-CoA reductase activity in monocyte-derived macrophages (MDM)
      from 12 control and 3 homozygous sitosterolemic subjects. The cells were cultured
      up to 7 days in media devoid of plant sterols, but containing increasing amounts
      of serum cholesterol. Before culture, MDM from the homozygous sitosterolemic
      subjects contained 22% more total sterols than cells from control subjects. Plant
      sterols and stanols represented 15.6% of MDM total sterols in sitosterolemic
      cells, but only 3.8% in control cells. After 7 days of culture in 10% delipidated
      serum (DLS) (20 microg/mL cholesterol, no sitosterol), all plant sterols were
      eliminated so that cells from both phenotypes contained only cholesterol. When
      DLS was replaced with fetal bovine serum (FBS) (300 micromL cholesterol), with
      and without addition of 200 microg/mL LDL, cholesterol levels in MDM from
      sitosterolemic subjects increased 108% (P <.05) compared with a 65% increase (P
      <.04) in control MDM cultured similarly. MDM HMG-CoA reductase activity from the
      3 sitosterolemic subjects, which was significantly lower than controls at
      baseline (24 +/- 3 v 60 +/- 10 pmol/mg/min, P <.05), was not downregulated by
      increased cellular cholesterol levels, as observed in control cells. Control MDM
      were also cultured in medium that contained 10% DLS and was supplemented with 100
      microg/mL cholesterol or sitosterol dissolved in ethanol or the ethanol vehicle
      alone. In contrast to cellular cholesterol accumulation, which significantly
      downregulated HMG-CoA reductase activity (-53%, P <.05), the increase in cellular
      sitosterol up to 25.1% of total sterols did not change MDM HMG-CoA reductase
      activity. Evidence of a normal HMG-CoA reductase protein in sitosterolemic cells,
      which was not derepressed upon removal of cellular sitosterol, and the failure of
      cellular sitosterol to inhibit normal HMG-CoA reductase activity argue against
      feedback inhibition by sitosterol as a mechanism for low reductase activity in
      this disease. The larger accumulation of sterols and inadequate downregulation of
      HMG-CoA reductase in MDM may be mechanisms for foam cell formation and explain,
      in part, the increased risk of atherosclerosis in sitosterolemia.

PMID- 11586499
TI  - Effect of norepinephrine on the urinary excretion of purine bases and oxypurinol.
AB  - To examine whether norepinephrine affects the plasma concentrations and urinary
      excretion of purine bases and oxypurinol, we orally administered allopurinol (300
      mg) to 5 healthy subjects and 9 hours later intravenously administered
      norepinephrine (12 to 20 microg/kg body weight), which causes a more than 10 mm
      Hg increase in diastolic pressure for 2 hours. Norepinephrine decreased the
      urinary excretion of uric acid by 33% (P <.01), oxypurinol by 32% (P <.01), and
      xanthine by 51% (P <.01), as well as the fractional clearance of uric acid by 32%
      (P <.01), oxypurinol by 24% (P <.05), and xanthine by 21% (P <.05) when measured
      1 to 2 hours after administration. These results indicate that norepinephrine
      decreases the urinary excretion of uric acid, oxypurinol, and xanthine, probably
      via hemodynamic change. It is also suggested that the hypouricemic effect of
      allopurinol may be more potent than that expected in gout patients with enhanced
      sympathetic tone, such as in salt-sensitive hypertension.

PMID- 11586500
TI  - The synergistic hypocholesterolemic activity of the potent cholesterol absorption
      inhibitor, ezetimibe, in combination with 3-hydroxy-3-methylglutaryl coenzyme a
      reductase inhibitors in dogs.
AB  - Ezetimibe (SCH 58235) and SCH 48461 are potent cholesterol absorption inhibitors,
      which cause significant decreases in plasma cholesterol levels in cholesterol-fed
      animals and in humans with hypercholesterolemia. These compounds selectively
      block intestinal uptake and absorption of cholesterol. These cholesterol
      absorption inhibitors cause modest, inconsistent reductions in plasma cholesterol
      levels in animals fed cholesterol-free chow diets. Although, these compounds
      block cholesterol absorption and increase neutral sterol excretion, chow-fed
      animals compensate for the loss of biliary cholesterol by increasing hepatic
      cholesterol synthesis. Therefore, we determined the effect of SCH 48461 and
      ezetimibe in combination with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)
      reductase inhibitors in chow-fed dogs. A synergistic reduction in plasma
      cholesterol was observed in chow-fed dogs given SCH 48461 (0.1 mg/kg/d) and the
      HMG CoA reductase inhibitor, lovastatin (5 mg/kg/d). Neither SCH 48461 nor
      lovastatin alone affected plasma cholesterol levels. Their combination for 14
      days caused a 36% reduction in plasma cholesterol levels from 129 mg/dL to 83
      mg/dL (P <.05). Ezetimibe (0.007 mg/kg/d) also caused synergistic reductions in
      plasma cholesterol levels in chow-fed dogs when combined with HMG CoA reductase
      inhibitors for 2 weeks (5 mg/kg lovastatin -50%; 2.5 mg/kg pravastatin -41%; 5
      mg/kg fluvastatin -60%, and -30% with low doses of simvastatin and atorvastatin 1
      mg/kg). The combination of this class of cholesterol absorption inhibitors with
      an HMG CoA reductase inhibitor should be very effective clinically at reducing
      plasma cholesterol levels, even with reduced dietary intake of cholesterol.

PMID- 11586501
TI  - Testosterone, sex hormone-binding globulin, and body composition in young adult
      African American and Caucasian men.
AB  - This study examined the diurnal variation in circulating total and free
      testosterone and sex hormone-binding globulin (SHBG) levels in young adult
      African American and Caucasian men in order to investigate whether there are
      differences in the secretion of these plasma hormones in populations at different
      risks of developing prostate cancer as they age. A significant and similar
      diurnal rhythm for total and free testosterone was found for both groups. Serum
      levels of total testosterone were 29.4% and 23.9% lower at 8:00 PM than at 8:00
      AM in African American and Caucasian men, respectively. Significantly higher
      serum levels of total testosterone (P<.01) and SHBG (P <.02) were found in the
      African American than in the Caucasian men in both the morning and evening,
      whereas free testosterone levels were similar in both groups. The higher SHBG
      levels appear to have an environmental/metabolic basis in that the waist
      circumference, waist-to-hip ratio, and fasting insulin concentration were lower
      (P <.05) in African Americans than in Caucasians. In summary, these data indicate
      that racial differences in central adiposity in men are established in early
      adulthood and influence circulating SHBG and thereby testosterone levels. In
      light of the findings by others that SHBG increases cyclic adenosine
      monophosphate (cAMP) production in the prostate and that cAMP-dependent protein
      kinase A is a coactivator of the androgen receptor, these studies provide a
      possible mechanism by which circulating androgens may contribute to the increased
      risk for prostate cancer among African American men.

PMID- 11586502
TI  - Study of the effect of changing glucose, insulin, and insulin-like growth factor
      I levels on serum corticosteroid binding globulin in lean, obese, and obese
      subjects with glucose intolerance.
AB  - We have previously described that serum corticosteroid binding globulin (CBG)
      concentrations are associated with insulin secretion. The present study was
      designed to evaluate the effects of changing insulin concentrations, both
      endogenous and after exogenous insulin administration, on circulating CBG levels
      in vivo. Serum CBG concentrations were measured during an insulin-modified
      frequently sampled intravenous (IV) glucose tolerance test (FSIVGT) in 14 lean
      and 19 obese otherwise healthy subjects with varying degrees of glucose
      tolerance. Acute insulin response to glucose (AIRg) correlated significantly with
      serum CBG concentrations at time 0 (r = -.38, P =.029), 22 minutes (r = -.41, P
      =.01), 50 minutes (r = -.41, P =.01), and 180 minutes (r = -.39, P =.02). Insulin
      sensitivity (S(I)) was not associated with serum CBG concentration at time 0 (r =
      -.16, P = not significant [NS]), but correlated significantly with CBG
      concentration at 22 minutes (r = -.41, P =.02) and 50 minutes (r = -.35, P =.048)
      of the FSIVGT. In lean subjects, serum CBG concentration decreased significantly
      after IV insulin from 37.9 +/- 5.4 to 35.4 +/- 3 mg/L (P =.02) and returned to
      basal levels thereafter. In contrast, obese, glucose-tolerant subjects had lower
      CBG levels than lean and obese glucose intolerant subjects (33.8 +/- 3.0 v 37.9
      +/- 5.4 and 39.8 +/- 4.4 mg/L, respectively), and their serum CBG concentrations
      remained unchanged during FSIVGT. Mean serum-free insulin-like growth factor-I
      (IGF-I) concentrations steadily declined from 1.21 +/- 0.81 to 0.8 +/- 0.36
      microg/L during the FSIVGT, and this effect was restricted to lean subjects.
      Basal serum-free IGF-I did not correlate with CBG levels at time 0, but
      correlated inversely with the serum CBG concentrations at 22 minutes (r = -.36, P
      =.04). Stepwise multivariant analysis showed that AIRg (P =.035) and S(I) (P
      =.046), but not free IGF-I levels, independently contributed to 28% of CBG
      variance at 22 minutes. These results suggest that insulin, but not IGF-I,
      constitutes an important negative regulator of CBG liver synthesis. Endogenous
      and exogenous insulin do not affect serum CBG concentrations in insulin-resistant
      obese subjects with preserved or decreased insulin secretion. Obese glucose
      tolerant subjects are hypothesized to exhibit tonically inhibited serum CBG
      levels. In contrast, in lean subjects, the higher the insulin secretion the lower
      the serum CBG concentration. The mechanisms of this CBG inhibitory effect exerted
      by insulin and its implication on cortisol homeostasis and fat distribution in
      humans await further investigations.

PMID- 11586503
TI  - Certification--an old and new story.

PMID- 11586504
TI  - Stability of plasma total homocysteine concentrations in EDTA-whole blood kept on
      ice.
AB  - In recent years there has been increasing interest in monitoring plasma total
      homocysteine concentration (tHcy), as a risk factor for thrombotic disorders. One
      of the significant preanalytical factors that can affect the reliability of tHcy
      measurements is the generation of homocysteine by erythrocytes in vitro, prior to
      the separation of plasma from cells. We measured changes in tHcy from EDTA-whole
      blood kept on ice and at room temperature for three hours. Compared to the tHcy
      in plasma from EDTA-whole blood that was processed immediately after collection,
      there was no significant change in tHcy in samples kept on ice for up to three
      hours prior to processing (mean change = -0.1 +/- 0.24 umol/L, p = 0.2). In
      contrast, tHcy in samples kept at room temperature increased by 0.7 +/- 0.2
      mumol/L per hour, p < 0.001. We conclude that tHcy is stable in EDTA-whole blood
      for at lest three hours, provided that the tubes are kept on ice until they are
      processed.

PMID- 11586505
TI  - The role of the laboratory in detecting inhalant abuse.
AB  - OBJECTIVE: To provide an overview of inhalant abuse including the extent of the
      problem, types of products abused, modes and signs of abuse, pharmacology and
      effects of volatile substances, the role of the laboratory, and interpretation of
      laboratory results.

PMID- 11586506
TI  - Effects of a hemoglobin-based oxygen carrier (HBOC-201) on coagulation testing.
AB  - Polymerized bovine hemoglobin (HBOC-201) is currently under investigation as an
      alternative to blood banked human red cells. Due to the dark red, hemolyzed
      appearance of HBOC-201, we sought to describe the effects of HBOC-201 on
      coagulation analyzers that perform prothrombin times (PT), activated partial
      thromboplastin times, fibrinogen, and antithrombin. Pooled normal plasma was
      combined with HBOC-201 to achieve plasma hemoglobin levels of 1.4, 2.6 3.8, 4.8,
      and 6.2 g/dL. Results for each test from HBOC-201 prepared plasmas were compared
      to saline matched controls. Two consecutive absolute result differences of > 10%
      between saline controls and HBOC-201 samples were used for determining
      interference on test accuracy by the concentration of HBOC-201. Mechanical
      detection methods (fibrometer, STA, CS-190) and the MDA-180 were less affected by
      increasing levels of HBOC-201 than optical detection devices for all test
      parameters.

PMID- 11586507
TI  - Laboratory test utilization in the diagnosis of hypercoagulability.
AB  - OBJECTIVE: To determine the appropriateness and utility of laboratory tests
      ordered by physicians for evaluation of hypercoagulability. DESIGN: Retrospective
      review of patient charts was performed to collect information on patient
      demographics, clinical history, coagulation testing, interpretation of results,
      and clinical decisions. SETTING/SAMPLE: Subjects included all patients from a 400
      bed acute care hospital who had a laboratory workup for hypercoagulability within
      the most recent 12-month period. Thirty-four patients whose medical records were
      available and whose clinical history included thrombosis were included in the
      study. MAIN OUTCOMES/CONCLUSIONS: Eighty-two percent of the patients had a
      familial and/or acquired risk factor for thrombosis. Over 40% had abnormal
      coagulation test results. Up to one-third of the tests were ordered and performed
      while the patient was on anticoagulant therapy. In over 50% of the cases with
      abnormal results, the physicians' notes did not mention the abnormality or the
      abnormal result was considered normal. These results indicate that although
      physicians are selecting the appropriate patients for laboratory test workup for
      hypercoagulability, the testing is being performed at an inappropriate time after
      the thrombotic event and the results of laboratory tests are often not utilized
      in patient diagnosis and management.

PMID- 11586508
TI  - Thrombotic risk and laboratory testing.

PMID- 11586509
TI  - Hemostatic changes associated with normal and abnormal pregnancies.
AB  - Routine hemostatic laboratory tests lack sensitivity and are of little value in
      the detection of the pregnancy associated hypercoagulable conditions. Assays for
      F 1 + 2, AT levels, TAT complex, APC activity, FPA, D-Dimers, tPA, plasminogen,
      PAI 1, and PAI 2 are more specific for fibrin formation and lysis. Monitoring
      these tests along with fibrinogen and platelet counts provides important
      information for the early detection of hemostatic activation and for monitoring
      the severity of the condition. Early detection and therapy is essential for
      limiting the deleterious complications of pregnancy. Advances in research, the
      development of new tests such as the TM assay and gene analysis, as well as
      highly skilled personnel, are required for the providing of quality pre and
      postnatal healthcare.

PMID- 11586510
TI  - A guide for diagnosis of patients with arterial and venous thrombosis.
AB  - Inasmuch as coagulation laboratories are involved in providing a diagnosis for
      underlying causes of venous and arterial thrombosis, we present a comprehensive
      review of the biological properties and functions of the components of the
      hemostatic system as they relate to the diagnosis of arterial and venous
      thrombosis. Moreover, as coagulation laboratories are necessary to evaluate the
      success of initial treatment modalities and to provide guidance for supplemental
      therapeutic intervention, we include information on antiplatelet and
      antithrombotic therapy. Included in clinical coagulation testing are assays that
      evaluate the potential of blood to form clots and tests for platelet numbers and
      platelet functions. Clot-based assays directly detect the biological activity of
      procoagulant factors and fibrinogen; chromogenic substrate assays evaluate
      proteolytic activities of clotting as well as fibrinolysis enzymes; and specific
      antibodies measure the concentrations of coagulation and fibrinolysis enzymes in
      plasma. Genetic testing is rapidly becoming incorporated into the clinical
      routine. The prothrombin time (PT), activated partial prothrombin time (APTT),
      and thrombin time (TT) are screening assays that measure the clotting times of
      recalcified whole blood or platelet-poor plasma. In addition to their function as
      screening assays, PT, APTT, and TT are the backbone of all the specialized clot
      based assays for factor activities and for the indirect measurement of inhibitory
      antithrombin and protein C activities. Molecular markers related to hemostasis
      and fibrinolysis consist of proteins or peptides that indicate an ongoing
      physiological or abnormal process related to clot formation, thrombosis, vascular
      damage, or drug effect. Molecular markers are currently identified by means of
      specific antibodies prepared against them. The list of hemostatic molecular
      markers is rapidly growing. Most of the assays developed for molecular marker
      measurement, with the notable exception of the d-dimer assay, are typically used
      in clinical research.

PMID- 11586511
TI  - Disseminated intravascular coagulation (DIC).
AB  - DIC is a life-threatening complication of several disease states. It is
      characterized by systemic activation of the hemostasis system. In many instances
      the release of tissue factor (TF) from endothelial cells or other circulating
      cells triggers the system. Initially, the increased activation can be compensated
      for by the natural inhibitor systems, a state referred to as compensated DIC. As
      the trigger persists, inhibitors will be consumed leading to more coagulation. In
      this process many clotting factors, most notably fibrinogen and platelets are
      consumed, resulting eventually in a complete breakdown of the hemostasis system.
      This results in a profuse and diffuse bleeding tendency or decompensated DIC. The
      term consumptive coagulopathy denotes this process. Of crucial importance is the
      fate of fibrin that is formed from fibrinogen by thrombin. If the fibrinolytic
      system is insufficiently activated, fibrin will be deposited in the
      microcirculation leading to MODS. This will not occur if the fibrinolytic system
      is fully activated. The clinical suspicion of DIC must be confirmed by laboratory
      tests and decreasing fibrinogen levels and platelet counts support the diagnosis.
      The determination of D-dimer, fibrin(ogen) split products (FSP) and soluble
      fibrin monomer (FM) further support the diagnosis. FM suggest the presence of
      thrombin, FSP the generation of plasmin, and D-dimer, both thrombin and plasmin.
      While the tests are not specific for DIC, they can be helpful, in the proper
      clinical setting, to diagnose decompensated or acute DIC. The tests are not
      useful for the diagnosis of compensated DIC, except for D-dimer, FSP, and FM if
      elevated. Compensated DIC can be diagnosed by molecular markers of in vivo
      hemostasis activation, such as thrombin-antithrombin (TAT) complexes, prothrombin
      fragment 1 + 2 (F 1 + 2), or plasmin-antiplasmin (PAP) complexes. For the
      treatment of DIC it is imperative to remove the triggering underlying disease.
      The consumption of coagulation constituents can be corrected by cryoprecipitate,
      platelet concentrates, and fresh frozen plasma, if needed. This may reduce the
      bleeding tendency. Arrest of the activated hemostasis system by heparins, either
      subcutaneous in low doses or intravenous in therapeutic doses, is only
      recommended in patients with compensated DIC. If the patient bleeds, heparins
      should not be given. The administration of concentrates of natural
      anticoagulants, i.e., antithrombin, protein C, or tissue factor pathway inhibitor
      are safer than heparins since they do not exacerbate the bleeding tendency. These
      concentrates were found to be very effective in animal models of DIC; human
      experience is still limited. Generally, the earlier treatment is initiated, the
      better the patient's prognosis.

PMID- 11586512
TI  - Toward a tobacco-free society in Japan.
AB  - Tobacco is one of the major preventable causes of death and disability. This is
      widely known in both Japan and the USA, and although the smoking rate in the USA
      is decreasing, that in Japan remains high. The tobacco histories of these two
      countries, which provide the background to this difference, are herein compared.
      The antismoking movement is becoming more vociferous in both countries. Publicity
      regarding of the dangers of smoking, warning signs on tobacco packages, the
      introduction of antismoking devices, a ban on commercials for tobacco-related
      products on TV and the radio, no-smoking seats on airplanes, and litigation
      against the tobacco industry have all been introduced. However, major differences
      remain between these two countries. The tobacco industry in the USA has been a
      private company since it was first established. Courts have ordered the tobacco
      industry to pay compensation for damage to health resulting from tobacco. Smoking
      is strictly restricted inside buildings. Advertisements for nicotine gum and
      nicotine patches and reports on the dangers of smoking are regularly broadcast.
      In the case of Japan, the government at first nationalized the tobacco industry,
      and then made it a private company, although the government still holds two
      thirds of its stock. Moreover, it established the Tobacco Business Law to support
      the company. The main purpose of antismoking campaigns in Japan is a partial ban
      on smoking. On the basis of these differences between the two countries regarding
      the history of tobacco, the antismoking movement in Japan has yet to choose which
      path to take.

PMID- 11586513
TI  - The new public long-term care insurance system and feeling of burden among
      caregivers of the frail elderly in rural Japan.
AB  - The present study was conducted to investigate the factors related to the
      feelings of burden (i.e., stress) among caregivers of the frail elderly in rural
      Japan after the introduction of the new public long-term care insurance system in
      2000. Forty-one out of 42 caregivers answered a self-administered questionnaire
      (i.e., the Japanese version of the Zarit Caregiver Burden Interview (ZBI))
      regarding their caregiving situation. Compared with lightly burdened caregivers
      (n = 20; ZBI > or = 41), those heavily burdened (n = 21; ZBI < or = 40) attended
      the frail elderly with greater numbers of behavioral disturbances (2.2 +/- 2.6
      vs. 0.6 +/- 1.0, p = 0.02) and those with dementia (60.9% vs. 39.1%, p = 0.08).
      Heavily burdened caregivers spent a longer time with the elderly (17.9 +/- 6.1
      hours vs. 11.8 +/- 8.4 hours, p = 0.01) as well as in providing for their
      physically care (14.0 +/- 7.9 hours vs. 8.6 +/- 8.2 hours, p = 0.04), thus having
      less time to go out unaccompanied by their patients (1.1 +/- 1.6 hours vs. 2.4 +/
      2.3 hours, p = 0.04). Such caregivers tended to be depressed (70.0% vs. 42.9%, p
      = 0.08), although they used more social services (5.2 +/- 2.0 vs. 3.7 +/- 2.1, p
      = 0.03) than the lightly burdened caregivers. In addition, more than half of
      caregivers (56.1%) in the present study were depressed. This rate was higher than
      the rates in our studies before the introduction of the new public long-term care
      insurance system (a rural town: 53.3%, an urban town 46.6%). Furthermore, the
      number of social services used by caregivers did not seem to increase after the
      introduction of this insurance system (before: 4.1 +/- 2.0, after: 4.4 +/- 2.1).
      These findings suggest that the quantity and quality of social services for the
      frail elderly and their caregivers may not suffice even after the introduction of
      the new public long-term care insurance system.

PMID- 11586514
TI  - [Basic study about the development of the hybrid-artificial liver support system
      using human hepatoma cell lines (Hep G2, Huh 7): effects on liver functions by
      extracellular matrix (type I collagen) in monolayer culture].
AB  - The risk of xenozoonosis infections poses the greatest obstacles against the
      clinical application of hybrid-artificial liver support system (HALSS). To
      resolve this issue, we used human hepatoma cell lines (Hep G2, Huh 7) in a type I
      collagen-coated monolayer culture system, and analyzed liver specific functions
      such as ammonia removal and albumin synthesis capacity. Ammonia removal activity
      (nmol/10(6) nuclei/hour) and albumin synthesis activity (microgram/10(6)
      nuclei/day) were upregulated in both Hep G2 and Huh 7 by type I collagen-coated
      monolayer culture. In particular, Hep G2 cultured in type I collagen-coated
      monolayer demonstrated relatively high ammonia removal and albumin synthesis
      capacity. These results indicate the possibility of the application of human
      hepatocytes to HALSS.

PMID- 11586515
TI  - Alteration of regional cerebral metabolism in patients with cirrhosis in positron
      emission tomography.
AB  - To evaluate the alteration of cerebral blood flow and oxygen metabolism in
      cirrhosis, we measured regional cerebral blood flow (rCBF), cerebral metabolic
      rate for oxygen (rCMRO2), and oxygen extraction fraction (rOEF) in twelve
      patients with cirrhosis (six with a history of hepatic encephalopathy and six
      without) and six age-matched controls using positron emission tomography.
      Regional CBF in whole brain was not different in cirrhotic patients from that in
      controls. In six cirrhotic patients with a history of hepatic encephalopathy,
      rCMRO2 was significantly lower in the frontal, temporal, parietal and occipital
      cortices, hippocampus, thalamus, cerebellum and brain stem, than that in each
      region of controls. On the other hand, rCMRO2 in six cirrhotic patients without a
      history of hepatic encephalopathy did not differ from the controls in all regions
      except for the frontal cortex. Regional OEF in cirrhotic patients without a
      history of hepatic encephalopathy was higher in the hippocampus and striatum than
      that in each region of controls. Among twelve cirrhotic patients, rCMRO2 in the
      occipital cortex and striatum correlated directly with plasma leucine levels, and
      rCMRO2 in the striatum directly correlated with plasma valine levels. Regional
      CMRO2 in the frontal cortex, temporal cortex, parietal cortex, white matter as
      well as brain stem correlated inversely with plasma phenylalanine levels, and
      rCMRO2 in the occipital cortex correlated inversely with plasma tyrosine levels.
      Brain oxygen metabolism is impaired in cirrhotic patients with a history of
      hepatic encephalopathy, but preserved in those without a history or in the early
      stage of cirrhosis. Reduced oxygen metabolism is related with altered amino acid
      metabolism.

PMID- 11586516
TI  - [Urinary tract infections, heart failure and driving. 21st Annual Meeting on
      Gerontology, Paris, October 12-13, 2000].

PMID- 11586517
TI  - [Management of asymptomatic carotid stenosis].

PMID- 11586518
TI  - [How to determine the diagnosis of Helicobacter pylori infection in the
      elderly?].
AB  - PURPOSE: The real prevalence of Helicobacter pylori (H. pylori) infection is
      difficult to determine in the elderly because of the frequency of drug intake
      (antibiotics or anti-secretory drugs). The aim of this study was to evaluate the
      diagnostic performance of five tests in the elderly. METHODS: The study
      population consisted of consecutive patients undergoing a routine endoscopy
      between August 1998 and December 1999. We evaluated the diagnostic performance of
      four tests in all of the included patients: culture and histology of biopsy
      specimens, serology (ELISA) and urea breath test (13C-UBT). Detection of H.
      pylori antigens in stool samples (HpSA) was realized in a subgroup. Patients were
      considered H. pylori + when result for culture was positive or when two tests
      were positive. RESULTS: One hundred and sixty-seven patients were included in
      this study (55 men, 112 women; mean age: 85.6 +/- 5.1 years). Only 38 (22.8%)
      patients were H. pylori+. Test performances showed the following results:
      serology sensitivity: 90.9% (IC 95%: 75.6-98.1) versus 86.9% (IC 95%: 63.6-96.9)
      for culture versus 77.8% (IC 95%: 60.8-89.9) for histology and 74.3% (IC 95%:
      56.7-87.5) for 13C-UBT. Eighty-nine (53.3%) took antibiotics or anti-secretory
      drugs, only 13C-UBT performances decreased significantly (sensitivity: 94.4%
      [72.7-99.8] versus 52.9% [27.8-77]; P < 10(-6)). When gastric or duodenal ulcer
      were endoscopically diagnosed in older patients, both histology and 13C-UBT could
      not improve the diagnosis of H. pylori infection. HpSA was realized in 107
      patients (sensitivity: 74.1%, specificity: 98.7%). We showed no statistical
      difference between HpSA performances and drug intake. CONCLUSION: Diagnostic
      performances decreased in older patients especially because of drug intake.

PMID- 11586519
TI  - [Risk factors and incidence of venous thromboembolic disease in internal
      medicine: prospective descriptive study on 947 hospitalized patients].
AB  - PURPOSE: The thromboembolic risk is difficult to evaluate in medical inpatients
      because of the multiplicity of risk factors. The lack of scientific data leads to
      a certain empiricism in selection of patients who need a preventive treatment.
      METHODS: All patients hospitalised in an internal medicine department were
      included during 34 months. The pathogenic mechanism of risk factors (venous
      stasis or hypercoagulability) was analysed as well as their progress (transient
      or permanent risk factors) and their pathogenic weight (major risk factor or
      not). Three levels of embolic risk (high, intermediate, low) were identified. A
      preventive treatment was initiated only for patients at high or intermediate
      risk. A clinical screening for thromboembolic events was performed daily.
      Therefore, we have excluded patients who needed a hypocoagulant treatment.
      RESULTS: Nine hundred and forty-seven patients were included. Age (over 60) was
      the most frequent permanent risk factor (70%). Bed rest was the most frequent
      transient risk factor responsible for venous stasis. Fifty percent of patients
      had a transient and permanent risk factor and needed a preventive treatment
      according to our selection criteria. The incidence of thromboembolic events was
      0.4% in the high-risk treated group and 0.2% in the low-risk non-treated group.
      CONCLUSIONS: Venous stasis factors are the more frequent risk factor in internal
      medicine, perhaps because of the increasing number of geriatric patients. The
      incidence of thromboembolic disease is low in high-risk inpatients when a
      preventive treatment is performed.

PMID- 11586520
TI  - [Non-simultaneous malignant lymphoma and antiphospholipid syndrome: 4 cases].
AB  - OBJECTIVE: We report four cases of non-synchronous antiphospholipid syndrome
      (APS) and malignant lymphoma, which highlight the complex relationship that seems
      to exist between these illnesses. METHODS: In a retrospective study conducted in
      two departments (internal medicine and clinical hematology) of a university
      hospital, we collected all observations of patients with both APS and malignant
      lymphoma diagnosed throughout the past decade. RESULTS: An association of APS
      with malignant lymphoma was recorded in three female and one male patient, median
      age 42.5 years at the time of diagnosis of the first disease. In each case, the
      primary APS was diagnosed, with arterial thrombotic events in three cases and
      venous thrombotic events in one case. One patient had isolated IgG
      anticardiolipin antibody, whereas the others had a combination of IgG
      anticardiolipin antibody and lupus anticoagulant with or without IgG anti-beta 2
      glycoprotein I antibody. One patient also had an acquired inhibitor to factor
      VIII:C and a chronic C virus hepatitis. The mean time apparently separating the
      two illnesses ranged from 18 months to 9 years, but in two cases the diagnosis of
      APS was delayed due to a progressive, atypical, neurological onset. In two
      instances, the APS took place at a distance from a cured malignant lymphoma
      (Hodgkin's disease and nodal large cell B-cell lymphoma), whilst in the others it
      preceded a B-cell lymphoma (nodal and cutaneous, small cells and primary hepatic,
      large cells). Treatment resulted in complete haematological response in both
      cases, with disappearance of anticardiolipin antibody and lupus anticoagulant in
      the latter following a double autologous peripheral blood stem cell
      transplantation. In addition, late carcinomas (breast, kidney, thyroid) were seen
      in two patients. CONCLUSIONS: Our data indicate that the diagnosis of a malignant
      lymphoma should be considered in patients with a primary APS and peripheral lymph
      node enlargement or unexplained constitutional symptoms. Conversely, a late onset
      of arterial or venous thrombotic diathesis after a malignant lymphoma may
      indicate not only late relapse of malignant lymphoma but also a subsequent APS.

PMID- 11586521
TI  - [Cardiovascular manifestations of systemic elastorrhexis].
AB  - INTRODUCTION: Systemic elastorrhexis or Gronblad-Strandberg-Touraine syndrome is
      a rare inherited disease characterized by a generalized elastic tissue dysplasia
      and polymorphic clinical features, with the main tissues affected being
      cutaneous, ocular and arterial. CURRENT KNOWLEDGE AND KEY POINTS: Usual
      cardiovascular complications of this entity include ischemic heart disease,
      renovascular hypertension and atherosclerotic peripheral vascular disease. Some
      cases of restrictive cardiomyopathies and valvular disease have been reported.
      Coronary artery disease, often with early onset, is seen in approximately 20% of
      cases. FUTURE PROSPECTS AND PROJECTS: This review of the literature concerning a
      rare cause of cardiopathy underlines the need to search for underlying
      elastorrhexis in the clinical setting of early onset and severe coronary artery
      disease or arteriopathy, especially in the absence of vascular risk factors. This
      hereditary disease has been traced to chromosome 16p13.1 and may in the future be
      easily diagnosed, bypassing the need for cutaneous biopsy.

PMID- 11586522
TI  - [New indications of ivermectin].
AB  - INTRODUCTION: Ivermectin is a semi-synthetic derivative of a family of
      macrocyclic lactones. This drug has a broad-spectrum anti-parasitic effect
      against various nematodes and ectoparasites. CURRENT KNOWLEDGE AND KEY-POINTS:
      Onchocerciasis and lymphatic filariasis are common indications. More recently
      ivermectin has been recommended in the treatment of strongyloidiasis and scabies.
      FUTURE PROSPECTS AND PROJECTS: Promising results have been shown in the treatment
      of ascariasis, cutaneous larva migrans, loiasis and head lice.

PMID- 11586523
TI  - [Association of disseminated lupus erythematosus and Crohn's disease].
AB  - INTRODUCTION: Association of Crohn's disease and systemic lupus erythematosus is
      infrequent. We report an observation of Crohn's disease that appeared in an 18
      year-old woman followed-up for systemic lupus erythematosus for four years.
      EXEGESIS: The patient had all the clinical, biological and histological criteria
      of Crohn's disease and systemic lupus erythematosus was diagnosed according to
      the American Rheumatism Association criteria. On the base of this observation, we
      discuss the digestive manifestation of systemic lupus erythematosus and
      extradigestive manifestations of Crohn's disease. CONCLUSION: The immunological
      background of both diseases was proposed to explain the mechanism of this rare
      association.

PMID- 11586524
TI  - [Isolated neurologic disorders disclosing Biermer's disease in young subjects].
AB  - INTRODUCTION: In young subjects, the discovery of a cobalamine deficiency
      (Biermer's disease) at the time of neuropsychiatric disorders even of isolated
      MRI anomalies is a rare event (less than 0.01%). EXEGESIS: We report two
      observations of cobalamine deficiency, in patients 30 and 37 years old, revealed
      by acroparesthesia and spontaneous hypersignal in the T2 sequence of MRI and by a
      peripheral sensitive neuropathy respectively. CONCLUSION: The neuropsychiatric
      demonstrations of pernicious anemia are polymorphic with, sometimes, isolated
      spinothalamic attacks. The MRI can contribute to the diagnosis but more often
      leads to an erroneous diagnosis. Our observations are of special interest because
      symptoms occurred apart from supplementation of folates and recovered ad integrum
      with an early treatment by vitamin B12.

PMID- 11586525
TI  - [Anterior compartment syndrome of the forearm caused by exercise: unusual cause
      of recurrent episodes of acute effort rhabdomyolysis].
AB  - INTRODUCTION: An effort-related compartmental syndrome is well known in the leg,
      but may be present infrequently, acutely or chronically in the anterior
      compartment of the forearm. EXEGESIS: We report a case of a 32-year-old man who
      presented four times after climbing exercises a bilateral compartment of the
      forearm, unusual because of the observation of rhabdomyolysis, but without
      irreversible damage. Clinical information and follow-up on two acute and 14
      chronic cases were reexamined, showing a homogenous presentation. He refused
      fasciotomy because he stopped athletic activities. Measurement of intramuscular
      pressure after exertion was useful for diagnosis. CONCLUSION: A local effort
      related pain must call to mind a chronic compartment syndrome of the forearm,
      which may risk incurring the acute form, with irreversible lesions of muscle and
      nerve, and possibly renal failure because of rhabdomyolysis.

PMID- 11586526
TI  - [A leg disease in a situation of emergency].

PMID- 11586527
TI  - [Mycobacterium avium complex septicemia: a new cause of thrombocytopenic
      thrombotic purpura].

PMID- 11586528
TI  - [Recurrent methemoglobinemia: look for repeated use of poppers].

PMID- 11586529
TI  - [Autoimmune diseases and vaccination against hepatitis B: should our patients be
      vaccinated?].

PMID- 11586530
TI  - [Unusual complication of primary Goujerot-Sjogren syndrome: interstitial
      cystitis].

PMID- 11586531
TI  - [Renal localization of periarteritis nodosa].

PMID- 11586532
TI  - [Diverticular sigmoiditis and false increase of CKMB isoenzymes: diagnostic trap
      to keep in mind].

PMID- 11586533
TI  - Tragedy hits home. Healthcare executives among the casualties of the terrorist
      attacks.

PMID- 11586534
TI  - Most are accounted for. Hours, place in tower save many empire employees.

PMID- 11586535
TI  - Priorities change in dramatic way. Defense, antiterror policies to replace
      Congress' healthcare agenda, observers say.

PMID- 11586536
TI  - Blood drives, not lobbying efforts.

PMID- 11586537
TI  - An overwhelming response. Within hours of the disaster, medical supplies were on
      their way to N.Y., D.C.

PMID- 11586538
TI  - Unexpected gifts. Flight ban slows but doesn't stop organ transplants.

PMID- 11586539
TI  - Normal business takes back seat.

PMID- 11586540
TI  - West coast facilities ready and waiting. Hospitals on heightened security cope
      with shortages, bomb threats.

PMID- 11586541
TI  - Medical personnel respond. Physicians across the nation eager to volunteer.

PMID- 11586543
TI  - 2001 up & comers.

PMID- 11586544
TI  - Ready, willing and able. Providers united to treat the victims of terrorism, but
      they wanted more patients.

PMID- 11586545
TI  - A profitable practice. Wis. system shows that owning doc groups doesn't have to
      be a financial drain.

PMID- 11586546
TI  - Disaster teams mobilize. System works, but units find few survivors to aid.

PMID- 11586547
TI  - Clinical evaluation and management of acute infectious diarrhea in adults.
AB  - Acute infectious diarrhea is a major global health problem. Issues for the
      developed and developing regions of the world differ. Awareness of disease
      pathophysiology and epidemiology are essential, however, for clinical evaluation
      and management. The immense human and economic burden imposed by acute diarrhea
      illness can be addressed only by thoughtful strategies aimed at prevention as
      well as cost-efficient evaluation and treatment.

PMID- 11586548
TI  - Infectious diarrhea in children.
AB  - Infectious diarrhea in children remains an important cause of morbidity in North
      America with rotavirus, nontyphoidal salmonella, Campylobacter and Giardia being
      the predominant pathogens in children younger than 5 years. Knowledge of the
      epidemiology of the diarrheal illness in a community together with the clinical
      information are necessary when determining the extent of investigation. Oral
      rehydration remains the mainstay of therapy and antibiotics are reserved for
      specific clinical situations and infections.

PMID- 11586549
TI  - Infectious diarrhea in the elderly.
AB  - Infectious diarrhea is an important disease in the elderly. Some basic principles
      have been outlined, as follows. In the elderly: Infectious diarrhea is an
      underappreciated health problem. There is a higher mortality rate and case
      fatality rate compared with younger persons. Infectious diarrhea is most often
      associated with group settings (e.g., nursing homes and skilled nursing
      facilities) or antibiotic use. Infectious diarrhea may be associated with
      abnormal immune function (i.e., immunosenescence). Certain bacterial infections
      are commoner (e.g., C. difficile, E. coli O157:H7, and Salmonella). Some
      infections behave differently (e.g., Salmonella). Prompt and adequate rehydration
      measures are crucial. The institution of appropriate contact isolation and
      infection control measures is crucial in group settings.

PMID- 11586550
TI  - Infectious diarrhea in human immunodeficiency virus.
AB  - Chronic HIV-associated diarrhea is currently a field in flux. Improved
      noninvasive diagnostic tests, improved pathogen-specific regimens, and better
      empiric therapies may change some of the assumptions used to select algorithms
      for diagnostic evaluation and management. Any shift in the cause of diarrhea from
      pathogen-associated to idiopathic or a reduction in the overall incidence of
      diarrhea would have considerable impact. It is unclear how significant the
      problem of pathogen relapse in previous responders will become. Existing studies
      reviewed in this article show that the high diagnostic yield of endoscopy when
      stool tests are negative, coupled with significantly better outcomes when
      pathogens are identified, support the current practice of routine endoscopic
      evaluation. There currently are scant data on the economic impact of HIV
      associated diarrhea as it relates to pathogen-specific and empiric therapy in the
      era of protease inhibitors. Such data would be integral to future evaluation of
      the impact of diagnostic and therapeutic strategies.

PMID- 11586551
TI  - Traveler's diarrhea.
AB  - This article presents a review of causes, presentation, and diagnosis of
      traveler's diarrhea. Treatment and prevention of this common problem is described
      in some detail. Finally, a practical and cost-effective approach to evaluating
      and treating a returning traveler is presented.

PMID- 11586552
TI  - Infectious causes of chronic diarrhea.
AB  - Chronic diarrhea can be seen in association with specific pathogens, usually
      parasites and occasionally some bacteria. This article reviews pathogens causing
      chronic diarrhea in immunocompetent individuals and provides a rational
      diagnostic approach.

PMID- 11586553
TI  - Laboratory approaches to infectious diarrhea.
AB  - Future applications of advanced molecular diagnostics in clinical laboratories
      will enhance significantly capabilities to diagnose bacterial, parasitic, and
      viral agents in the early course of disease through enhanced assay sensitivities
      and specificities and improved turnaround times, theoretically leading to more
      timely and directed therapeutic intervention. Until such time, clinicians must
      continue to rely on clinical judgment and the diverse battery of traditional
      culture techniques, direct examination (including light microscopy and electron
      microscopy), and immunoassays that are available. Cost considerations and the
      ever-increasing array of infectious agents responsible for infectious
      gastroenteritis will continue to drive the development of practice guidelines to
      assist practitioners with reasoned and reasonable approaches to management of
      diarrheal illnesses.

PMID- 11586554
TI  - Infectious colitis excluding E. coli O157:H7 and C. difficile.
AB  - Colitic infection caused by a variety of organisms may have an extremely varied
      presentation, course, and treatment response. Current data have provided great
      insights into the pathophysiology of these various organisms and their clinical
      presentation, course, and treatment outcomes. As clinicians develop a better
      understanding of the colon, its immunologic defense mechanisms, and the virulence
      factors of such organisms, they will be better able to evaluate these infections
      as well as newer colonic infections yet unknown. It is important to know if and
      when to treat such organisms to prevent the dilemma of drug-resistant strains, as
      seen already in a variety of well-known infections, such as Campylobacter and
      others. Knowledge of such colonic targets will be more important in an era of
      ever-growing resistance to and wide use of antibiotic regimens.

PMID- 11586555
TI  - Escherichia coli O157:H7.
AB  - E. coli O157:H7 can cause potentially lethal illness in hosts of all ages. These
      patients often are evaluated and treated by gastroenterologists. The treating
      physician should administer adequate hydration, usually parenterally, and avoid
      the use of antibiotics and antimotility agents. The physician needs to notify
      immediately the appropriate public health authorities of the diagnosis and to
      ensure that the isolate is recovered by the microbiologist and forwarded for
      molecular linkage analyses.

PMID- 11586556
TI  - Clostridium difficile.
AB  - Clostridium difficile is a major cause of antibiotic-associated diarrhea and
      colitis. The incidence of infection with this organism is increasing in hospitals
      worldwide, consequent to the widespread use of broad-spectrum antibiotics.
      Pathogenic strains of C. difficile produce two protein exotoxins, toxin A and
      toxin B, that cause colonic mucosal injury and inflammation. Many patients who
      are colonized are asymptomatic, and recent evidence indicates that diarrhea and
      colitis occur in those individuals who lack a protective antitoxin immune
      response. In patients who do develop symptoms, the spectrum of C. difficile
      disease ranges from mild diarrhea to fulminant pseudomembranous colitis.
      Prevention of nosocomial C. difficile infection involves judicious use of
      antibiotics and multidisciplinary infection control measures to reduce
      environmental contamination and patient cross-infection. Ultimately, active or
      passive immunization against C. difficile may be an effective means of
      controlling the growing problem of nosocomial C. difficile diarrhea and colitis.

PMID- 11586557
TI  - Viral causes of diarrhea.
AB  - Viruses are important causes of diarrhea. In healthy adults, the main clinical
      manifestation is acute, self-limited gastroenteritis. Advances in molecular
      diagnostics have shown that epidemics of acute gastroenteritis most frequently
      are due to caliciviruses spread through contaminated food or through person-to
      person contact. Application of similar technology is needed to make a definitive
      statement about the role of such candidate viruses as rotavirus, astrovirus, and
      adenovirus as the cause of nonepidemic acute gastroenteritis in adults. Rarely a
      previously healthy adult gets acute CMV colitis. CMV and EBV mainly cause
      diarrhea in immunocompromised patients, however. Advances in prophylaxis and
      treatment have reduced the frequency and severity of these diseases. Acute
      infantile gastroenteritis is caused by rotavirus, calcivirus, astrovirus, and
      adenovirus. These viral diseases of the gut are seen by the physician as routine
      and rare clinical problems.

PMID- 11586558
TI  - Parasitic infections of the gastrointestinal tract.
AB  - This article updates recent advances in the body of knowledge of diagnosis and
      treatment of intestinal parasites. The articles focus on the manifestations of
      disease in the immunocompetent adult host from developed countries. Specific
      pathogens discussed are Giardia lamblia and Dientamoeba fragilis, Entamoeba
      histolytica, Entamoeba dipar, Blastocystis hominis, Cyclospora cayetanensis, and
      Cryptosporidium parvum.

PMID- 11586559
TI  - The role of antibiotics in the treatment of infectious diarrhea.
AB  - Infectious diarrhea is a significant cause of morbidity and mortality and a
      common complaint in clinical practice. Routine empirical use of antibiotics for
      infectious diarrhea should be avoided because of the self-limited nature of most
      cases, the cost of antibiotics, and the potential to worsen the already
      significant problem of antibiotic resistance of enteric pathogens. For patients
      with severe invasive or prolonged diarrhea or who are at high risk of
      complications, such as the elderly, diabetics, cirrhotics, and immunocompromised
      patients, empirical treatment with a quinolone antibiotic for 3 to 5 days can be
      considered. Antibiotic treatment can be highly effective for Shigella, ETEC, and
      V. cholerae infections, and metronidazole is indicated for C. difficile colitis.
      The impact of antibiotics for other specific pathogens is modest, and antibiotic
      therapy should be reserved for the same group of patients who would be considered
      for empirical treatment. The most significant problem in the antibiotic treatment
      of infectious diarrhea is the progressive increase in resistance among enteric
      pathogens; only the prudent use of antimicrobials in all areas of daily practice
      can limit or delay the impact of this serious problem.

PMID- 11586560
TI  - Biotherapeutic agents in the treatment of infectious diarrhea.
AB  - Biotherapeutic agents offer unique advantages over traditional treatments for
      infectious diarrhea, and several have been shown to be effective (Table 4). These
      therapeutic microbial agents are most effective in types of infectious diseases
      that are associated with a disruption of the normal intestinal microecology
      (e.g., AAD, C. difficile disease). The impact of biotherapeutic agents on
      rotaviral diarrhea is of special clinical importance because this is the most
      common cause of pediatric diarrhea, and there is no defined treatment. Strong
      efforts need to be made to limit antibiotic exposure in children. Biotherapeutic
      agents offer a safe and effective nonantibiotic method of treating this important
      pathogen, especially after the withdrawal of a rotaviral vaccine from the market
      by the FDA. However, for many biotherapeutic agents, well-done, placebo
      controlled trials still are lacking, and not all types of infectious diarrhea
      respond to these agents. Continued research in this innovative therapeutic area
      is warranted.

PMID- 11586561
TI  - [Combined multimodal treatment for liver and lung metastasis from colorectal
      cancer: a new therapeutic option?].
AB  - The authors analyse which therapeutic strategy to adopt on the basis of
      prognostic factors and staging of hepatic and pulmonary metastases from
      colorectal cancer. They underline the effectiveness of combined multimodal
      therapy in the treatment of very advanced metastatic stages. 218 patients with
      metastases from colorectal cancer (12 pulmonary and 206 hepatic metastases) were
      treated from January 1980 to October 2000. Among these patients, 159 underwent
      surgery (4 pulmonary and 155 hepatic resections), 16 were reoperated on for
      metastatic relapse, 14 with multiple metastases underwent locoregional therapy
      and 29, deemed unresectable initially, were treated with neoadjuvant chemo- and
      radiotherapy. In the operated patient group the 5-year actuarial survival rate
      was 22% with an operative mortality of 3.8% and a morbidity of 17.5%. The 16
      patients reoperated on for metastatic relapse had a 5-year actuarial survival of
      21% with an operative mortality of 6.2% and a morbidity of 15.8%. The 14 patients
      treated with locoregional therapy had a median survival of 6 months whereas the
      29 patients treated in two different periods with combined multimodal treatment
      had a response rate of 59.2%. Five patients had a complete response and 4 are
      currently disease-free. Surgical resection is at present the best known treatment
      for metastatic disease. In very advanced, as yet undisseminated stages, in which
      there is no surgical indication for metastases a neoadjuvant treatment is
      proposed if the primary tumour has already been completely resected. The aim of
      this therapeutic strategy, called combined multimodal therapy, is to obtain the
      disease regression with the aid of systemic chemo- and radiotherapy and to offer
      a chance of re-staging the disease.

PMID- 11586562
TI  - [Laparoscopic surgery of the colorectum: analysis of results of the National
      Registry of the Italian Society of Endoscopic Surgery and New Technologies
      (S.I.C.E.)].
AB  - The aim of this paper was to review the data from the Italian Registry of
      Laparoscopic Colo-Rectal Surgery sponsored by SICE. The Italian Registry was set
      up in January 1993 by the merging of two Registries existing since November 1991.
      Thirty-five centres, up to March 2001, had participated in the Registry, with
      2,793 patients recorded (F = 1,409, M = 1,384), 1878 for malignancy and 915 for
      benign diseases. The median age was 63.7 years. The conversion rate was 10.8%.
      Mortality was 0.6% (18 cases) and major abdominal complications occurred in 11.1%
      of patients. The reoperation rate was 5.1%. After a median follow-up of 59
      months, 16 patients (0.9%) presented abdominal wall metastases. Relapses occurred
      in 18.5% of patients after curative resections for rectal cancer, and in 12.7%
      after curative resections for colon cancer. Laparoscopic colo-rectal surgery has
      gained widespread acceptance. The reproducibility and safety of all the major
      laparoscopic colo-rectal procedures has been demonstrated. Nevertheless, the lack
      of long-term results of randomised trials in terms of oncological efficacy and
      the technical difficulties of the procedures suggests that laparoscopic colo
      rectal surgery should be performed only in referral centres by skilled surgeons.

PMID- 11586563
TI  - [Endothoracic goitre: anatomoclinical and therapeutic considerations].
AB  - Substernal goitre is a clinical condition in which the masin bulk of the enlarged
      gland is firmly located in the chest. The incidence of this pathology ranges in
      literature from 1.7% and 30%. This study examines 230 cases of substernal goitre
      out of a total 5.362 operations performed from 1965 to 2000, for thyroid gland
      pathologies (4.36%). According to their experience the Authors propose a
      classification based on the anatomical location of the goitre: right, left,
      anterior and posterior goitre are therefore identified. The surgical procedures
      performed include 136 subtotal thyroidectomies (59.1%), 59 emithyroidectomies
      (25.7%) and 23 total thyroidectomies (10%). In 12 cases the operation was
      confined to removal of the mediastinal mass (5.2%). The cervical approach was the
      only surgical access route used in all the patients, regardless of the different
      anatomical variants. Appreciable venous stasis, due to the mediastinal mechanical
      obstruction exerted by the goitre, was always evident at the operation. In order
      to limit the risk of bleeding during operation, careful hemostasis of the major
      vascular pedicles must be performed. Any attempt to legate the smallest vessel,
      should be avoided since it is a difficult, useless and time-consuming procedure.
      Minor bleeds promptly stop as soon as the pathological mass is removed. Ligation
      of the vascular pedicles can be easily achieved; in this way, the goitre is freed
      from its anatomical connections and the surgeon can safely manage the substernal
      portion of the mass. The mortality reported in this study was 0.43% (one patient
      died 30 days postoperatively due to respiratory complications), whereas the
      morbidity rate was 2.6%.

PMID- 11586564
TI  - [Cancer of the right colon: biological features and extent of the surgical
      resection].
AB  - Right-sided colon cancer therapy is based upon right hemicolectomy, which is a
      well established surgical technique. Considering the possibility of biological
      diversity in cancer arising from the caecum, ascending colon and transverse
      colon, this retrospective study analysed age, sex, grading, T, N, M and mortality
      to evaluate the biological characteristics of the cancers and their level of
      local and general diffusion with a view to establishing any correlation between
      these characteristics and the advisability of employing different surgical
      procedures for the different sites. Cancer arising from the sites considered does
      not seem to present different biological aspects and therefore a different
      surgical procedure is not authorized. Our data show that a significant majority
      of cancers are diagnosed at an advanced stage as compared to earlier stages (P <
      0.05) and that early detection of these cancers is the best way of improving the
      prognosis.

PMID- 11586565
TI  - [Intermediate resection and distal pancreatectomy for benign neoplasms of the
      pancreas: comparison of postoperative complications and costs].
AB  - The middle pancreatic resection for benign pathology of the pancreas has been
      proposed as an advantageous alternative to the distal pancreatectomy, even though
      the risk of complications is greater. The purpose of the present study is to
      compare the cost and intra and perioperative impact for the 2 procedures. All
      patients with benign neoplasia of the body and tail of the pancreas operated on
      from 1990-1999 were selected from our computer archives, 21 patients underwent an
      intermediate resection and 64 a distal pancreatectomy. Operative time, units
      transfused, perioperative complications, post-operative stay and cost were
      compared. Statistical analysis revealed that the 2 operations are not
      significantly different in the intra-operative period. Comparing serious
      complications, the percentage of pancreatic fistulas (33% vs. 11%; P < 0.03) and
      average hospital stay (21.2 +/- 11.7 days vs. 15.5 +/- 7.1 days; p = 0.009) are
      greater for the middle than distal resection, respectively. In cases with post
      operative complications the hospital stay is even more significant (middle 31.8
      +/- 10.3 days vs. 19.1 +/- 7.6 days; p = 0.0002). The economic margin of residual
      costs, calculated by using the difference of DRG (no 192) and average post
      operative costs, is similar for the 2 procedures in cases with normal post
      operative courses, (intermediate Euro 2890.02; distal Euro 3181.9), while in
      cases with complications (DRG no 191), the difference increases (intermediate
      Euro 8670.11; distal Euro 12788.94). The middle pancreatic resection in respect
      to the distal pancreatectomy presents a greater technical difficulty when you
      take into account the longer post-operative course, the increased difficulty in
      treating complications and the increased costs.

PMID- 11586566
TI  - [Primary hyperparathyroidism: diagnostic and therapeutic trends].
AB  - The most interesting aspects of parathyroid disease are the increased incidence
      of primary hyperparathyroidism, which nowadays is diagnosed more and more
      frequently through the casual discovery of hypercalcaemia, the various diagnostic
      methodologies used, the ongoing debate as to the function of parathyroidectomy in
      asymptomatic patients and the new video-assisted surgical techniques which have
      recently been developed. The authors retrospectively review 31 consecutive cases
      of primary hyperparathyroidism. The clinical onset was characterised in 26 cases
      by an osteoarthralgic syndrome associated with renal and biliary pathology. Five
      cases were asymptomatic. Prior to surgery, all patients underwent both
      biochemical and instrumental tests. MIB scintigraphy was found to yield the most
      reliable diagnosis, leading to identification of 83.6% of diseased parathyroids.
      As regards surgical treatment, 29 cases were treated with a simple
      parathyroidectomy, 1 with a bilateral inferior parathyroidectomy and 1 with a
      thyroid lobectomy. Associated thyroid surgery was performed in 8 cases for
      concomitant thyroid disease: 1 total thyroidectomy, 2 subtotal thyroidectomies
      and 5 lobectomies. In 3 cases radioimmunoguided surgery was used. There were no
      cases of mortality, and 9.6% of patients presented specific morbidity
      characterised by some degree of paraesthesia. As stated by other researchers, the
      authors argue that MIBI scintigraphy is the most reliable test for the diagnosis
      of hyperparathyroidism and that surgical treatment is the first choice for
      symptomatic primary hyperparathyroidism. The surgical strategy depends on the
      abnormality underlying the hyperparathyroidism: in the event off an adenoma, a
      bilateral exploration of the neck and removal of the diseased parathyroid are
      required; in the case of hyperplasia, a subtotal parathyroidectomy is necessary
      with marking of the residual parathyroid which will simplify any possible
      reoperation; in the event of carcinoma, a thyroid loboisthmectomy and ipsilateral
      parathyroidectomy are performed with removal of the fatty tissue of the antero
      superior mediastinum and ipsilateral cervical functional lymphadenectomy.

PMID- 11586567
TI  - [Analysis and long-term survival in sternectomy with plastic reconstruction for
      primary and secondary neoplasms of the sternum].
AB  - From January 1980 to December 1999, 88 patients underwent surgical resection for
      tumours involving the sternum. Thirty were males, aged 16 to 76 years, and 58
      females, aged 23 to 78 years (mean ages: 48 and 53 years, respectively). There
      were 30 primary malignant tumours, 28 local recurrences or distant metastases
      from breast cancer, 16 other tumours, and 14 radionecroses. Total sternectomy was
      performed in 8 cases, subtotal (> 50%) in 32, and partial (< 50%) in 48.
      Concurrent en-bloc resection of the anterior ribs was performed in 61 patients,
      and of the clavicle in 13. Resection was extended to the lung in 22 patients, to
      the pericardium in 17, to both in 2, to the diaphragm and pericardium in 4. Bone
      and soft tissue defects were repaired with prosthetic material associated with a
      muscular or myocutaneous flap in 55 patients, with prosthetic material alone in
      13 cases, with a muscular or myocutaneous flap in 5 cases, and with other
      techniques in the remaining patients. The resection was considered to be
      macroscopically radical in 78 patients and palliative in 10 cases. There was one
      perioperative mortality and significant morbidity was limited to 13 cases. Among
      the patients treated with a radical intent, 48 were alive and disease-free at the
      end of follow-up. The 10-year survival rate was 85% in primary tumours. For
      breast cancer relapses, 10-year survival was the same as 5-year survival (41.8%).
      In our experience, an en-bloc sternal resection for a primary or secondary
      tumour, followed by plastic repair using prosthetic material and/or a
      myocutaneous flap, is a safe, effective treatment. This intervention permits the
      execution of extensive radical resections for sternal neoplasms, as well as
      enabling the patient to obtain a better quality of life. Long-term survival after
      radical sternectomy also depends on the histological type of the tumour.

PMID- 11586568
TI  - [Indications for splenectomy in the surgical treatment of gastric cancer].
AB  - The extent of lymphadenectomy in the treatment of gastric cancer is still a
      matter of debate. Splenectomy, which has to be performed using the common
      surgical techniques to remove the lymph nodes of the splenic hilus, is part of
      this problem. The indications for splenectomy in the treatment of gastric cancer
      are examined, considering the results in terms of operative mortality and
      morbidity and long term survival. The Authors analyze a consecutive series of 129
      patients who underwent total gastrectomy with D2 or D3 lymphadenectomy for
      gastric cancer. Forty-seven splenectomies were performed among 79 patients
      submitted to total gastrectomy. Splenectomy did not influence the perioperative
      mortality. Morbidity was higher in the patients who underwent splenectomy (33.3%)
      than in the patients without splenectomy (28.12%). This difference was not
      statistically significant. Five-year survival was higher in the group that did
      not undergo splenectomy (37.6% vs 27%) without any significant difference. Also
      considering the results in literature, splenectomy is associated with an increase
      in morbidity, and, for some authors, also in mortality, without any significant
      improvement in long-term survival. The indication for splenectomy in gastric
      cancer is based on an accurate evaluation of the localization and the depth of
      the parietal infiltration of the tumor.

PMID- 11586569
TI  - [Acute pancreatitis: resultos of a diagnostic-therapeutic protocol in 80
      consecutive cases].
AB  - The treatment of acute pancreatitis cannot be standardized in the absence of a
      prompt diagnosis and of an accurate severity and prognostic score. This study,
      based on 80 consecutively observed patients, compared the aetiological, clinical,
      diagnostic (laboratory and imaging) and prognostic data used to select the most
      appropriate therapy for each patient. The results confirm that the Ranson score
      shows a satisfactory prognostic relationship between the number of positive
      parameters and the severity of the disease. Ultrasound, which is useful for
      defining the aetiologic factors and in the follow-up of peripancreatic effusions,
      has proved to be limited as a means of imaging abnormalities of the pancreatic
      parenchyma. CT scans are confirmed as being the only method of accurately
      demonstrating the presence of necrosis and of evaluating its effective extent.
      ERCP was performed as soon as possible in the presence of biliary stasis or of
      suspect ultrasonographic signs. Surgical treatment proved necessary only in 7.5%
      of cases, on each occasion to drain infected necrotic foci. Promptness of the
      surgical indication plays an important role in the outcome of necrosectomy and
      drainage performed with the closed technique. Mortality was limited to 1.25% in
      our series. A correct diagnostic approach together with prompt treatment can
      reduce the mortality rate of this disease to a minimum.

PMID- 11586570
TI  - [Dunbar's syndrome and aorto-mesenteric compression. A casual association?].
AB  - Celiac artery compression syndrome and superior mesenteric artery syndrome are
      two rare diseases, extensively documented in the literature, with a pathogenesis
      which is still controversial. Their association never been carefully studied and
      only one such case has been reported. For this reason we reviewed our experience
      from january 1974 to december 2000, including 57 patients diagnosed with coeliac
      artery compression syndrome and 27 patients with superior mesenteric artery
      syndrome. We found the presence of both syndromes in 6 patients. All 6 were
      submitted successfully to a duodeno-jejunal bypass and decompression of the
      coeliac artery. In this paper we analyse the pathogenesis, clinical presentation,
      diagnosis and treatment of these syndromes emphasising their common aspects. The
      association of the coeliac artery compression syndrome and superior mesenteric
      artery syndrome has never been thoroughly studied because of their rarity. The
      lack of recognition of this association may, in some cases, justify the
      controversial results reported in the surgical treatment of these syndromes.

PMID- 11586571
TI  - [Ano-rectal traumatic lesions. Etiology and treatment].
AB  - From January 1976 to December 2000, in the Surgical and Specialistic Sciences
      Department, Ist Chair of Surgical Physiopathology, University of Bari, we
      observed 13 cases of ano-rectal trauma. Except in wartime, these traumas are
      unusual. The aetiology is variable. In our experience we found 3 lesions due to
      firearms (24%), 2 patients with polytrauma after car accidents (15%), 3
      iatrogenic lesions (24%), 1 lesion due to compressed air (7%), and 4 lesions due
      to objects used for autoeroticism (30%). Timely diagnosis and treatment were
      essential for a good outcome. The surgical choice was based on the patient's
      condition, the aetiology of the lesion and its anatomical site. We constructed 7
      temporary colostomies and performed 2 Hartmann's operations. In 4 patients we
      extracted objects from the rectum. Four patients died.

PMID- 11586572
TI  - [Endoluminal pressure: risk factor for anastomotic dehiscence in rectal
      carcinoma. Preliminary results].
AB  - The aim of this work was to evaluate the risk factors for anastomotic leakage
      with particular reference to endoluminal pressures in patients undergoing surgery
      for colorectal cancer between february 1998 and september 2000. In this
      preliminary report a total of 120 patients were identified; 96 patients were
      treated with a total mesorectal excision (with anastomosis less than 10 cm from
      the anal margin) for rectal cancer and 33 with a partial mesorectal excision
      (with anastomosis of the superior rectum) for rectosigmoid carcinoma. The
      leakages were observed in 10.4% of patients and the incidence of this
      complication was 15.6% in patients with rectal cancer. Using a transanal tube (7
      x 2 cm) which reduces endoluminal pressure close to the anastomosis, a
      significant reduction in the number of leakages was observed. The authors suggest
      that the transanal tube represents a useful aid in resolving the problem of
      anastomotic leakage in rectal cancer and stress the importance of this simple,
      cheap surgical technique.

PMID- 11586573
TI  - [Blood coagulation changes in patients with post-splenectomy persistent
      thrombocytosis].
AB  - To clarify the possible role of persistent thrombocytosis after splenectomy as
      being a predisposing factor causing thromboembolism. Blood coagulation profiles
      were studied in 35 patients (20 M and 15 F, mean age 42 +/- 17.5) suffering from
      thrombocytosis (> 500,000/dl) who underwent splenectomy for non-malignant and non
      traumatic diseases. Seventy healthy subjects acted as a control group. Tests were
      performed 6 months after the operation and for both groups (patients and
      controls) blood samples were collected for: platelets, fibrinogen, PT, APTT, AT
      III, plasminogen, F1 + 2, t-PA and DNA analysis for F V, F II and MTHFR. After
      one year all subjects were controlled for thrombocytosis, genomic abnormalities
      and venous thrombosis. All the analyses were performed according to the
      Statistical Package for Social Science. The significance of the differences in
      means was evaluated by non-parametric tests, differences with a P value < 0.05
      being considered significant. Increased plasma levels of fibrinogen, D-dimer, F1
      + 2 and PAI-1 were found in the patients compared with the control group. TPA was
      significantly lower in the patients than in the controls. At the one year follow
      up, two patients with genetic polymorphism had suffered deep venous thrombosis.
      Our findings indicate that splenectomy contributes to abnormal platelet
      aggregation and endothelial cell activation with hypercoagulability.

PMID- 11586574
TI  - [Current problems of the surgical treatment of rectal cancer: analysis of the
      literature and personal experience].
AB  - The surgical procedure is a crucial factor in preventing local recurrence in
      rectal cancer, and total mesorectal excision (TME) particularly is widely
      accepted as being associated with a decreased local recurrence rate. In this
      study, concerning 187 patients with rectal cancer, we compare conventional
      surgery, performed in 140 patients from 1979 to 1993, with a standardised TME
      procedure in 47 patients over the period from 1994 to 1998. The first group not
      treated by TME were operated on for 56 (40%) tumours of the upper rectum and 84
      (60%) of the lower rectum; 35 (25%) were Dukes' A, 77 Dukes' B and 28 (20%)
      Dukes' C. 42 abdominoperineal amputations (30%) and 98 anterior resections (70%)
      were performed. The second group in which TME was performed comprised 17 (36%)
      tumours of the upper rectum and 30 (64%) of the lower rectum, 8 (17%) in stage I
      AJCC (Dukes' A), 16 (34%) in II (B) and 23 (49%) in III (C). 9 abdominoperineal
      amputations (19%) and 38 anterior resections (81%) were performed, 8 (21%) with
      an ultra-low anastomosis. In the first group of patients we observed 28 local
      recurrences (20%) and a 5-year disease-free survival in 50% of cases. In the
      second group we achieved a decreased rate of local recurrence (10.6%) which is
      about half that observed after conventional surgery, but there was no significant
      difference in survival. These data confirm the effectiveness of TME in reducing
      local recurrence rate, according to the literature; in future this procedure can
      get to reconsider the role of adjuvant therapy in the management of rectal
      cancer.

PMID- 11586575
TI  - [Late post-traumatic diaphragmatic hernia: unusual cause of colonic occlusion].
AB  - Traumatic diaphragmatic rupture is not an uncommon problem, particularly in the
      last few years because of the increasing number of road accidents, improved
      diagnostic techniques and resuscitation techniques after serious traumas. In a
      certain number of cases, post-traumatic diaphragmatic hernias may become
      clinically manifest only months or years after thoracic or abdominal trauma and
      are still a challenge to surgeons because of the vague clinical symptoms and the
      diagnostic difficulties involved. The Authors report a case of acute colon
      occlusion due to diaphragmatic hernia 24 months after thoraco-abdominal trauma.
      None of the radiological or endoscopic examinations demonstrated the presence of
      diaphragmatic hernia. Laparoscopy showed a diaphragmatic rupture with
      incarceration of the left colonic segment. The laparoscopic procedure was
      converted for technical reasons and the diaphragmatic defect was closed with a
      primary suture.

PMID- 11586576
TI  - [Large villous adenoma of the colon in carcinomatous transformation: colonic
      resection after endoscopic excision].
AB  - Large colonic villous adenomas are benign neoplasms capable of malignant
      transformation with a higher frequency than other adenomas. Such transformation
      often requires surgical therapy after endoscopic resection. The aim of the
      present study was to establish the indications for surgery in a series of 13
      cases of large colonic villous adenomas initially submitted to endoscopic
      resection. The patients (8 males and 5 females; mean age; 62 years) were observed
      over the period 1993-2000. All endoscopic resections were performed using the
      piecemeal technique. In 7 cases there were 2 endoscopic sessions and in one case
      3; a single case of post-endoscopic bleeding was treated conservatively. In 5
      cases, endoscopic resection was deemed not to be radical and these patients were
      submitted to surgical resection. Histology on the surgical specimens revealed 2
      cases of carcinoma (T1 and T2, respectively), confirmation of colonic villous
      adenoma in 2 cases and the presence of inflammatory tissue in 1 case. Among the
      patients treated with endoscopic resection alone one death occurred at two years
      due to lung and systemic metastases probably due to the malignant adenoma. After
      a review of the literature and on the basis of their own experience, the authors
      stress the importance of a combined pathological and endoscopic approach to
      establish when surgery is required.

PMID- 11586578
TI  - Caval extension of the right renal vein in cadaveric renal transplantation using
      the ETS 45 endoscopic stapler.
AB  - A major technical difficulty encountered with the transplantation of a cadaveric
      right kidney is due to the short right renal vein. The transplant surgeon usually
      has two different options to deal with this: the first is to mobilize the
      external iliac vein, ligating the internal iliac vein and the small retroiliac
      veins, while the second option is to increase the length of the right renal vein.
      Right renal vein extension is usually preferred because it is easier to work
      with. The technique used was to construct a conduit with the vena cava that
      extends the cadaveric right renal vein using an endoscopic stapler (Ethicon
      Endopath Linear Cutter ETS45, cod. TSW 45) for thin/vascular tissues. This
      procedure has been used successfully in 11 of our 155 transplanted patients. We
      have seen no vascular complications as a result of the stapled conduit of the
      vena cava. We conclude that the endoscopic stapler for thin/vascular tissues is
      safe and easy to use in right renal vein extension.

PMID- 11586577
TI  - Solitary rectal ulcer syndrome: an unusual cause of rectal stricture. Case
      report.
AB  - Solitary rectal ulcer syndrome can be seen in both adults and children but
      frequently arises in the 3rd and 4th decades of life. The definitive aetiological
      cause is unknown. Its treatment is primarily medical except in cases presenting
      complications. In this report, we describe a case of solitary rectal ulcer
      syndrome complicated by rectal stricture.

PMID- 11586579
TI  - [Anoplasty with House advancement flap for anal stenosis after hemorrhoidectomy.
      Report of a clinical case].
AB  - Anorectal strictures may occur after anorectal surgery and in particular after
      surgical haemorrhoidectomy. Anal examination under general anaesthesia was
      recommended to evaluate the stricture and to choose the appropriate technique.
      The house advancement flap has been recently proposed for postsurgical anal
      stenosis repair. The house flap receives its blood supply through unnamed vessels
      extending through a fatty pedicle from the underlying external sphincter muscle
      and not from a skin or mucosal bridge like the other common flaps (Y-V and
      mucosal advancement flap). The aims of this study were firstly to report a case
      of post-haemorrhoidectomy anal stenosis in a 68-year-old man treated in our
      institution by house advancement anoplasty and secondly to evaluate the efficacy
      and safety of this new technique. The technique was totally successful in
      alleviating anal stenosis and maintaining faecal continence. House advancement
      anoplasty should be part of the armamentarium of colon and rectal surgeons for
      treating severe anal stenosis.

PMID- 11586580
TI  - Understanding giving patterns in communities of color.

PMID- 11586581
TI  - The organizational personality & HR outcomes.

PMID- 11586582
TI  - Gift planning in the year 2010: imagine the unimaginable. 2.
AB  - Philanthropy in general, and fund raising in particular, is changing. Such change
      is more radical than most recognize and certainly faster than most organizations
      are prepared for. Those that anticipate the change and adjust to it have a good
      chance of thriving. Those that fail to do so will struggle and may become
      irrelevant.

PMID- 11586583
TI  - Essential data for fund raising executives: what you don't know can hurt you.
AB  - The collecting, maintaining and dispensing of data is not a topic for the timid.
      Data collection can be a fundamental tool or an insidious fifth column within an
      organization. Fund-raising execs and CEOs will inevitably meet this issue, either
      head on through foresight and planning, or unexpectedly by means of a distressed
      donor or angry prospect.

PMID- 11586584
TI  - 12 trends for the 21st century.

PMID- 11586585
TI  - Are you running out of time?
AB  - In a perfect world we would all have a written daily plan of action that would be
      inviolate. Every task, every action, every conversation would be precisely timed
      to move us toward our ultimate personal goals. No one would trespass on our
      sacred schedule. But this is most definitely not a perfect world.

PMID- 11586586
TI  - Quick tips for writing and designing a good response card.

PMID- 11586587
TI  - ORYX data collection valuable but difficult and labor-intensive, some say.

PMID- 11586588
TI  - Safety profiles delayed by JCAHO but coming soon.

PMID- 11586589
TI  - Combined roles: balance clinical, financial responsibilities.

PMID- 11586590
TI  - Don't overlook CEO performance evaluations.

PMID- 11586591
TI  - New report confirms quality problems are extensive.

PMID- 11586592
TI  - IOM author notes 'differences in judgment'.

PMID- 11586593
TI  - Hundreds of hospitals part of safety survey.

PMID- 11586594
TI  - Physicians' office staff influence patient choice and satisfaction.

PMID- 11586595
TI  - Maryland hospital launches "second-generation" Website.

PMID- 11586596
TI  - A time to choose. The ministry should throw its resources into health care
      reform.

PMID- 11586597
TI  - Spirituality assessment in health care. In examining a patient's "objects of
      devotion," the clinician may find clues to an unhealthy lifestyle.

PMID- 11586598
TI  - Expanding service area. Third in a series examining revenue growth strategies in
      a difficult health care market.

PMID- 11586599
TI  - Naming the elephant in the room.

PMID- 11586600
TI  - Patient advocacy.

PMID- 11586601
TI  - "Integrity" and "compliance".

PMID- 11586602
TI  - Case study: personal and professional integrity.

PMID- 11586603
TI  - The buck stops here.

PMID- 11586605
TI  - The role of the professional.

PMID- 11586604
TI  - Organizational ethics case study: the Bon Secours Richmond contract renewal.

PMID- 11586606
TI  - The dynamics of value.

PMID- 11586607
TI  - Community networks. Community Hospice House, Merrimack, NH.

PMID- 11586609
TI  - We must make rural health care a high priority.

PMID- 11586610
TI  - New device destroys blood-borne pathogens.

PMID- 11586612
TI  - The four ages: we've only just begun.

PMID- 11586613
TI  - An emotional time. Counselors say most will recover, caution their profession.

PMID- 11586614
TI  - Physicians targeted. Some docs of Mideast descent attacked, suspended; group
      decries 'backlash'.

PMID- 11586615
TI  - Ready to deal in Albuquerque. Catholic Health Initiatives takes look at options
      including sale, joint venture.

PMID- 11586616
TI  - Healthcare buyers clubs.
AB  - When one shops for a computer or auto insurance, the AHA or the AMA probably
      isn't the first thing that comes to mind, but associations are getting into the
      business of product endorsements.

PMID- 11586617
TI  - This fever chart may turn up. Healthcare stocks, bonds may have bright future
      despite market sell-off.

PMID- 11586619
TI  - Worst-case scenario. Experts call on hospitals, agencies to be prepared.

PMID- 11586618
TI  - Business as unusual. N.Y.'s hospitals confronted by myriad problems.

PMID- 11586620
TI  - [Ganglion block in cardiopulmonary bypass surgery].
AB  - Ganglion blockers increase the antinociceptive defense in anesthesiological
      support of cardiopulmonary bypass operations for mitral and aortic valve failure.
      Benzohexonium decreased total peripheral vascular resistance, increased cardiac
      and stroke indexes, and increased systolic potency of the heart. Ganglionar
      blocking was associated with an increase of systemic oxygen transport,
      arrhythmias developed rarely, blood concentrations of epinephrine,
      norepinephrine, ACTH, vasopressin, and leukinferon were lower.

PMID- 11586621
TI  - [Brain protection in open heart surgery in patients with infective endocarditis].
AB  - Effect of nimotope on cerebral metabolism and incidence of mental disorders in
      patients operated on under forced ventilation of the lungs (FVL) was studied in
      32 patients subjected to replacement of mitral and aortic valves for infective
      endocarditis. Nimotope was used for preventing hypoxic disorders of the CNS. The
      drug was injected starting from the stage of operation before FVL. Cerebral
      hypoxia was diagnosed using lactate-oxygen index (LOI) and other cerebral
      metabolic coefficients. LOI increased in all patients immediately after FVL,
      being much higher in the patients without cerebral protection. Moreover, numerous
      neurotic and mental disorders were observed in this group of patients during the
      early postoperative period. By contrast, no mental disorders, disorders of memory
      or attention were detected in the patients treated with nimotope. These data
      indicate that nimotope decreases the unfavorable effect of FVL on the CNS
      function in patients with infective endocarditis. The difference of lactate
      content in arterial blood and in the internal jugular vein bulb and LOI can be
      used for the diagnosis of brain ischemia in heart surgery with FVL.

PMID- 11586622
TI  - [Cardiac right ventricular function and hemodynamics during resection of the
      lungs].
AB  - Right-ventricular function and hemodynamics were studied in 48 patients during
      resections of the lungs (lobectomy and pneumonectomy) under total noninhalation
      anesthesia. Approaches to compensation of circulation in resection of different
      volume of lung tissue were determined. The leading role of the diastolic function
      of the right heart ventricle in realization of hemodynamic response in
      pneumonectomy is revealed. Volumetric monitoring of right-ventricular function
      during extensive lung resections is highly informative.

PMID- 11586623
TI  - [Transcranial electric stimulation in anesthesiological support in emergency
      operations in patients with hypovolemia].
AB  - Hemodynamics was studied in 60 patients with pronounced initial hypovolemia,
      urgently operated on for acute gastrointestinal disease under conditions of 4
      anesthesia. In contrast to traditional anesthesia, transcranial electric
      stimulation (TCES) as a component of anesthesia stabilized hemodynamics without
      increasing the rate and volume of intraoperative infusion therapy. This makes
      total anesthesia with TCES preferable in urgent operations, particularly in cases
      when hypovolemia cannot be properly corrected before surgery.

PMID- 11586624
TI  - [Postoperative pain syndrome and its relationship with individual psychological
      features of personality].
AB  - A total of 120 patients subjected to planned operations for diseases of thoracic
      and abdominal organs and main vessels were examined for an objective evaluation
      of the postoperative pain syndrome. The psychological status of patients and its
      relationship with the painful syndrome and narcotic doses needed for pain arrest
      were studied. In the control (100 pts) the initial depression and postoperative
      pain were in direct correlation. Tetracycline antidepressant lerivone was used to
      confirm the results. Depression and the severity of postoperative pain decreased
      significantly in 20 patients.

PMID- 11586625
TI  - [Disorders of purine metabolism and the antioxidant system in obstetrical
      gynecologic sepsis].
AB  - Results of examinations of 360 patients with obstetrical gynecological sepsis are
      analyzed on the basis of ACCP/SCCM conference recommendations on the diagnosis
      and classification of sepsis. The patients were divided into 3 groups: with
      sepsis, severe sepsis, and septic shock. Parameters characterizing purine
      metabolism and lipid peroxidation were studied. Disorders in purine metabolism
      and activation of lipid peroxidation were detected in all patients and were the
      most severe in severe sepsis and septic shock.

PMID- 11586627
TI  - [Analysis of morphological changes in the spinal cord and ganglia of dogs after
      epidural administration of prosidol, clopheline and prosidol-clopheline
      combination].
AB  - Experiments were carried out on 22 mongrel dogs (12-20 kg). Group 1 consisted of
      5 dogs to which prosidol in a dose of 0.65 mg/kg was injected epidurally; group
      2, 5 dogs, clofelin (6.5 micrograms/kg) epidurally; group 3, 5 dogs, prosidol
      (0.65 mg/kg) + clofelin (6.5 micrograms/kg) epidurally. Control groups were as
      follows: 1) 5 intact dogs; 2) 2 dogs epidurally injected with 0.9% normal saline.
      Analysis of the spinal cord and ganglia in control groups showed no dystrophic
      changes in neurons. After epidural injections of prosidol, clofelin, or both only
      solitary cells with degenerative changes were detected or none at all. Nissle
      granules were evenly distributed in the cytoplasm of anterior and posterior
      spinal horn neurons in all control and experimental animals. The majority of
      ganglious cells in control and experiment had the nucleus and nucleolus. Hence,
      morphological analysis showed that epidural injection of prosidol, clofelin, and
      a combination of both caused no degenerative or necrobiotic changes in the
      anterior and posterior spinal horn neurons and in ganglious cells of spinal
      ganglia.

PMID- 11586626
TI  - [Correction of free radical processes by a succinic acid drug (reamberine) in
      intensive care of patients with acute neurotropic poisoning].
AB  - Sixty-six patients with acute poisonings with neurotropic toxins (soporiphics,
      neuroleptics, antidepressants, ethanol and its surrogates) were examined and
      treated. Clinical data and correction of disorders in free-radical processes in
      acute poisonings with these toxins indicate the efficiency of adding reamberine
      to combined therapy of this patient population.

PMID- 11586629
TI  - [Morphological and histochemical changes in the spinal cord after epidural
      administration of prosidol in dogs].
AB  - Morphological, histochemical, and histoenzymatic changes in the nervous tissue of
      the spine and spinal ganglia after epidural injection of narcotic analgetic
      prosidol were studied in acute experiment on 12 mongrel dogs. No negative effect
      of prosidol on neuronal structure and nervous tissue microcirculatory bed were
      observed in experimental vs. control animals. The type of changes and their
      direction in various compartments of the nervous system (spine and spinal
      ganglia) were similar in control and experimental animals.

PMID- 11586628
TI  - [Enzymatic activity in spinal cord neurons after epidural administration of
      clopheline in dogs].
AB  - Time course of the major enzymes (SDH, LDH, GPDHcyt, GPDHmit, AP) and protein
      synthesis (DNA, RNA) in spinal neurons and spinal ganglia after epidural
      injection of clofelin were studied in an acute experiment on dogs. No
      physiological or neurological disorders or depriming effect of clofelin on the
      major enzymatic systems and protein synthesis in nervous tissue of dogs were
      detected. Increased activity of AP in the spinal white and gray matter is worthy
      of note, which indicates intensification of active transport in spinal capillary
      epithelium after epidural injection of clofelin.

PMID- 11586630
TI  - [Ethical and legal problems in critical medicine].
AB  - The major ethical and legal problems in anesthesiology, intensive care, emergency
      and disaster medicine are discussed. Special attention is paid to violation of
      patient's rights, limits of intensive care and resuscitation, evaluation of
      iatrogenic complications and unfavorable outcomes from clinical physiological and
      legal viewpoints, and legal responsibility of anesthesiologists, intensive care
      specialists, and emergency physicians. Occupational hazards and protection of
      specialists in critical medicine are discussed.

PMID- 11586631
TI  - [Intracellular disorders in the dog myocardium in low cardiac output syndrome
      caused by massive hemorrhage, approaches to correction].
AB  - It was shown on dog experiments that disorders in the phosphorylation-proteolysis
      calcium transport system in the sarcoplasmatic reticulum of pathologically
      changed myocardium are an important component of cardiac activity depression in
      massive blood loss. Low cardiac output can be corrected by ammonium molibdate,
      phosphoprotein phosphatase inhibitor, and contrycal, proteolysis inhibitor.

PMID- 11586632
TI  - [Thyroid hormones and melatonin as means of antioxidant therapy].
AB  - The possibility of involvement of thyroid hormones and melatonin in cell
      protection from damage by active oxygen forms (hydroxyperoxide, superoxide
      radical, and hypochlorite) was investigated. The intensity of inhibition of
      luminol-dependent chemiluminescence induced by neutrophils and active oxygen
      forms in the presence of hormones was evaluated. Antioxidant activities of the
      enzymes were compared with that of glutathione. Probable mechanisms of
      antioxidant effect of the studied hormones are discussed.

PMID- 11586633
TI  - [Algorithm of cardiopulmonary resuscitation in a cardiological hospital].
AB  - Recent comments and amendments to routine algorithm of P. Safar's cardiopulmonary
      resuscitation, known as the ABCD principle, are critically analyzed. The primary
      mechanisms of thanatogenesis in sudden death in the majority of cases are not
      respiratory problems (requiring ABCD algorithm), but cardiac rhythm disorders.
      Based on their studies and practical and training experience, the authors suggest
      a new algorithm of cardiopulmonary resuscitation: UNIVERSAL, with the following
      steps: precordial stroke, indirect massage of the heart, forced ventilation of
      the lungs, venipuncture, electrocardiography, defibrillation by electric pulse
      therapy, electrocardiostimulation, and injections of adrenalin, atropine, and
      lidocaine. Introduction of this algorithm decreased hospital mortality of acute
      coronary patients, increased the rate of reanimation of suddenly dead patients,
      and reduced the incidence of iatrogenic complications of resuscitation.

PMID- 11586634
TI  - [Anesthesiological aspects in determining indications and contraindications for
      surgical interventions in patients with severe wounds and injuries in the post
      shock period].
AB  - Approaches to validation of indications and contraindications for interventions
      in wounded patients and victims were developed on the basis of many-year
      experience. The desirability of intervention is determined primarily by strategic
      tasks which it solves. The operation is to be performed despite severe clinical
      condition if it removes the cause of critical state or creates conditions for
      preventing life-threatening complications of the traumatic disease. All the rest
      interventions can be postponed till complete or partial compensation of vital
      systems.

PMID- 11586635
TI  - [Early diagnosis and intensive care of acute postoperative pancreatitis].
AB  - Diagnostic algorithm developed on the basis of multifactorial regression analysis
      is suggested for more objective diagnosis of acute pancreatitis after operations
      on the hepatopancreatoduodenal organs. This algorithm helps differentiate the
      strategy of intensive care in patients with pancreatitis, pancreatic disease, and
      uneventful postoperative period. It is impossible to single out the specific
      (pathognomonic) clinical signs of this complication during the immediate
      postoperative period. Hyperamylasemia and changes in other enzymes are important
      but not absolute markers of unfavorable course of disease.

PMID- 11586636
TI  - [Gas exchange disorders and their correction during the acute period of burn
      disease].
AB  - The criteria of early respiratory therapy in patients with isolated and combined
      thermal burns are accurately defined and the efficiency of such therapy is
      evaluated. Early respiratory therapy in the form of forced or assisted
      ventilation of the lungs stabilizes hemodynamics, improves oxygen transport and
      consumption, and eventually improves the results of treatment in patients with
      isolated and combined thermal burns.

PMID- 11586637
TI  - [Etiology and diagnosis of pneumonia in patients on artificial lung ventilation].

PMID- 11586639
TI  - [Total intravenous multicomponent anesthesia with diprivan infusion in a specific
      concentration in neurosurgical patients].
AB  - Total intravenous anesthesia (TIVA) with diprivane infusion in a purposeful
      concentration was carried out in 54 patients for various neurosurgical
      interventions. Purposeful concentrations of diprivane for induction and
      maintaining anesthesia were 1.5-2 times lower than those recommended by the
      manufacturer, which was due to effects of TIVA components fentanyl, clofelin, and
      diazepam, as well as patient's age, clinical status, and, probably, neurosurgical
      disease. Anesthesia was controllable and hemodynamically stable, the awakening
      was early.

PMID- 11586638
TI  - [Anesthesiological care of fiber colonoscopy in cancer patients].
AB  - Various methods of total anesthesia for colonoscopy in cancer patients, carried
      out in a outpatient setting, are compared. Diprivane and dormicum were used as
      monoanesthesia and in combinations with ketamine and fentanyl. Diprivane
      anesthesia was the optimal as regards the velocity of recovery of
      psychophysiological functions. Ketamine was acknowledged inefficient because of
      long awakening and psychotic effects.

PMID- 11586640
TI  - [Place of anesthesiology and intensive care among other medical specialties in
      Russia].

PMID- 11586641
TI  - [Concept of specialized training of nurses in anesthesiology and intensive care].
AB  - The need in improving the training of medical workers necessitated the
      development of the concept of vocational training of nurses in anesthesiology and
      intensive care. The key points of this concept were discussed and approved as the
      basis at the Seventh All-Russian Congress of Anesthesiologists and Intensive Care
      Specialists in September 2000 in St. Petersburg.

PMID- 11586643
TI  - [Variation cardiac intervalometry -- a component of neurophysiological
      monitoring].
AB  - The course of intraoperative period is retrospectively analyzed in patients
      operated on for bulky formations of the brain. Mathematical analysis of cardiac
      rhythm structure, performed using an original method within the framework of
      operation monitoring, detected early signs of disorders in adaptation systems,
      indicative of insufficient anesthesia and overrun physiological permissiveness
      during the main stages of operation. The results of the study extend our notions
      on the potentialities of traditional monitoring and improve the efficiency of
      neuroanesthesiological support and choice of surgical strategy.

PMID- 11586642
TI  - [Analysis of prehospital analgesia administered to victims with traumatic
      injuries].

PMID- 11586644
TI  - [Structural changes in the intraorgan hepatic arteries during experimental aortic
      coarctation].
AB  - Structural changes of intraorganic hepatic arteries were studied in 8 control
      dogs and 20 pups with hemodynamic model of aorta coarctation. Experimental
      animals were observed within the terms from 1 month to one year. Histological and
      morphological methods were used to assess the state of hepatic vessels. The
      investigations performed resulted in the discovery of the complex of adaptive and
      pathological changes in the hepatic arterial bed. The first were the reactive
      atrophy of the hepatic arteries wall with decrease of smooth myocytes number and
      parameters in the media and the appearance of musculo-elastic sphincters, Conti
      pillows and smooth myocytes bundles in the intima. The latter lied in the
      arterial and arteriolar wall sclerosis in liver. Pathological changes grow
      proportionally with the terms of the experiment.

PMID- 11586645
TI  - [Structural differences between the desmosome-like contacts in the chemical and
      afferent synapses of Mauthner neurons in the goldfish].
AB  - Comparative ultrastructural investigation of the desmosome-like contacts at
      chemical and mixed afferent synapses of the goldfish Mauthner neurons was carried
      out. It was revealed that these contacts at mixed synapses differed from those at
      chemical ones by thin transverse fibrillar bridges which cross the gap and
      connect two adjoining membranes of the junction. We suppose that these
      crossbridges together with gap junctional connexons may serve as a substrate for
      electronic coupling at mixed synapses demonstrated earlier.

PMID- 11586647
TI  - [Cardiomyogenesis in Rana ridibunda tadpoles during metamorphosis in normal
      conditions and after exposure to various concentrations of cadmium ions].
AB  - During metamorphosis period Rana ridibunda ventricular cardiomyocytes possess
      strong ability to adapt to altering developmental conditions, certain
      peculiarities of differentiation were observed during this process, cell death
      and mitotic activity increases. The action of different concentrations of cadmium
      ions on Rana ridibunda larvae changes interrelation and intensity of basic
      processes of cardiac muscular histogenesis, leading to differentiation disorders,
      suppression of proliferative activity and intensification of cardiomyocytes
      death.

PMID- 11586646
TI  - [Relationship between morphometric indices of the capillary network and lipid
      peroxidation in visual structures of human brain during aging].
AB  - At late stages of ontogenesis the density of functionally active capillaries
      grows smaller, their contact surface area and capillary bed characteristics
      increase. These changes are in certain reciprocal relations with the fall of
      activity of neuronal succinate dehydrogenase, increase of the number of primary
      heptantophilic products of lipid and decrease of secondary isopropanol-soluble
      lipids. The changes named are most pronounced in the visual cortex and lateral
      geniculate bodies.

PMID- 11586648
TI  - [Lymphoid structure in the mouse cecum wall during immunosuppression and its
      correction with liposomal agents].
AB  - The influence of liposomal preparation obtained from the Baikal seal fat on
      lymphoid structures in mouse coecum wall on the background of immunodepressive
      state induced by asathioprine was studied using microscopic methods and statistic
      analysis. It was demonstrated that asaphioprine administration caused decline in
      lymphoid serie cells, outgrowth of adipose tissue, causes destructive changes of
      lymphoid structures in the coecal wall. After the effect of liposomes on the
      background on the immune suppression morphological state of lymphoid structures
      was approximated to the normal state while the indexes of cellular composition
      returned to the level of control values which was conditioned by immunocorrecting
      properties of the drug studied.

PMID- 11586649
TI  - [Morphological analysis of dynamics of myeloid cells in cultured erythroblastic
      islets].
AB  - Morphological analysis of myeloid cells in cultures of erythroblastic islets (EI)
      was undertaken. All types of myeloid cells (except for myeloblasts) were present
      in EI preparations isolated from the rats bone marrow. Natural EI include all the
      cells of myeloid lineage in their "crown". In the course of in vitro cultivation
      the number of EI including mature granulocytes appeared increased, while the
      contents of EI associated with promyelocytes, myelocytes and metamyelocytes
      decreased. The data obtained is discussed in view of probable EI role in bone
      marrow myelopoiesis.

PMID- 11586650
TI  - [Morphofunctional changes in the thyroid gland after cyclophosphamide
      administration and their reversibility].
AB  - By using histological morphometric stereological and quantitative enzyme
      histochemical methods, structural and metabolic changes in thyroid gland after
      short-term treatment with high doses of cyclophosphamide (GY) were studied. Mice
      were treated with 400 mg/kg of GY every 48 h for up to 7 days(1-4 i.p.
      injections). To assess the effect of CY and its reversibility thyroids were
      studied on the day following each injection and 5-15 days after three injections.
      CY treatment caused significant dose-dependent structural and metabolic changes
      in thyroid gland which included vacuolization and destruction of thyrocyte apical
      cytoplasm, focal follicular wall destruction leading to the fusion of some
      follicles, reduction in volume fractions of epithelium with the condominant
      increase in volume fraction of colloid and stroma, decrease in follicular cell
      height, decline in both thyrocyte cytoplasmic NAD-H-diaphorase activity and
      vascular alkaline phosphatase activity. These changes were not completely
      reversible by day 15 after the last injection of CY.

PMID- 11586651
TI  - [Structural organization of the glandular apparatus of the cecum in aged and
      elderly persons].
AB  - By macro- and microscopic methods structural and functional peculiarities of
      glands of coecum were studied in 45 healthy people who died at the age of 60-92.
      It was demonstrated that glands of different regions of the coecal wall displayed
      significant morphological peculiarities. In zones of free, omental and
      mesenterial bands the density of coecal glands arrangement was in all cases
      higher than between bands. The length, cross section area epitheliocyte number of
      glands of the apical zone of crescent-shaped folds exceeded that of glands
      between the folds. Magnification of density of glands arrangement, their area and
      cross section epitheliocyte number was noted in the zone of ileocoecal valve.

PMID- 11586652
TI  - [General biological characteristics of physical development of school children
      from the city of Novosibirsk].
AB  - Anthropometrical data characterizing physical development of schoolchildren of
      Novosibirsk (7 years old boys and girls and 14-17 years old boys) were presented.
      Comparative analysis of the results obtained with the findings of the analysis
      performed by Scientific Research Institute of Hygiene, Ministry for Public Health
      in 1959, 1969 and 1976 have demonstrated elongation of body weight along with
      lower rate of body mass growth and the thoracic cage circumference. Growth and
      development acceleration of the children was considered within more global
      biological process--secular trend. Gracilization is a characteristic feature of
      the modern human organism development.

PMID- 11586654
TI  - Drying out: use of restorative drying techniques--Part Two.

PMID- 11586653
TI  - [Histophysiology of neocortical basket cells].
AB  - Basket cells (BC)--an exceptional category of cortical interneurons is a basic
      component of intercolumnar, lateral and callosal inhibition of pyramidal and
      nonpyramidal neocortical neurons. BC terminals--basket plexuses and pericellular
      nestles contact with bodies, axonal hillock and proximal regions of pyramidal
      neurons dendrites and double-bouquet cells, forming reciprocal relations with
      them in accordance with domen-selection principle. BC establish ties between each
      other and interconnect by means of autapses. The structure, neurochemical
      specialization and spatial organization of neocortical basket cells was
      described. Modern conceptions on histophysiology of basket cell inhibition were
      analysed basing on results of the authors original investigations and data
      available in literature. A hypothesis according to which basket plexus may be
      thought of as an inhibiting integrator, equaling excitation in a cluster of
      several pyramidal cells is under substantiation.

PMID- 11586655
TI  - An experiential learning simulation exercise for healthcare management students.
AB  - Preparing competent administrators to work in today's dynamic healthcare
      environment is a challenging task for contemporary educators. Experiential
      exercises in the classroom can contribute significantly to student training. This
      paper reviews the benefits to students of actively participating in simulations
      and role-plays, as well as the challenges in running such exercises. A simulation
      designed specifically for healthcare administration students is presented with
      details and implementation instructions. The intent of this article is to impart
      to other educators the learning experiences in running this particular simulation
      to inspire dialogue and program improvement. Readers are encouraged to create
      simulation exercises with optimum relevance for their students. Information to
      obtain e-mail versions of the simulation is also provided.

PMID- 11586656
TI  - The organizational context of ethical dilemmas: a role-playing simulation for the
      intensive care unit.
AB  - The allocation of health care resources often requires decision makers to balance
      conflicting ethical principles. The resource-constrained intensive care unit
      (ICU) provides an ideal setting to study how decision makers go about their
      balancing act in a complex and dynamic environment. The author presents a role
      playing simulation exercise which models ICU admission and discharge decision
      making. Designed for the class-room, the simulation engages a variety of ethical,
      managerial, and public policy issues including end-of-life decision making,
      triage, and rationing. The simulation is based on a sequence of scenarios or
      "decision rounds" delineating conditions in the ICU in terms of disposition of
      ICU patients, number of available ICU beds, prognoses of candidates for
      admission, and other physiological and organizational information. Students,
      playing the roles of attending physician, hospital administrator, nurse manager,
      triage officer, and ethics committee member, are challenged to reach consensus in
      the context of multiple power centers and conflicting goals. An organization
      theory perspective, incorporated into the simulation, provides insight on how
      decisions are actually made and stimulates discussion on how decision making
      might be improved.

PMID- 11586657
TI  - Training needs for physician leaders.
AB  - The results of a national panel survey of physician leaders are presented here.
      Although these perspectives are not drawn from a random national sample of all
      physician leaders, they do provide valuable insight from a group of key decision
      makers. Current technical and skill areas applicable to medical leadership, and
      projected future needs, are addressed. While medical leadership at present is
      focused on clinical medicine, perceptions of future directions for medical
      leadership suggests the increasing need for education related to specific
      technical skills as well as enhancement of personal characteristics. The results
      reported here help provide a platform for further elucidation of training needs
      for an audience of present and future physician leaders.

PMID- 11586658
TI  - Quality improvement in the curriculum: a survey of AUPHA programs.
AB  - During the past decade, healthcare organizations have responded to a changing and
      unstable healthcare environment by implementing Quality Improvement initiatives.
      The goal of these activities is to improve system performance and outcomes, both
      administrative and clinical. Many of the models for Quality Improvement have been
      adopted from the manufacturing sector and with modification, implemented within
      healthcare systems. Healthcare managers must now be able to compute run-charts,
      use statistical process control to measure variation within processes, develop
      flow-charts, and be knowledgeable about the development and interpretation of
      customer satisfaction surveys. Although Quality Improvement has been readily
      adopted by healthcare organizations, information is lacking about the preparation
      of new healthcare managers in regard to these modalities. A survey was created to
      assess the extent that students are being prepared to use the tools of Quality
      Improvement. The instrument was administered to undergraduate, graduate, and
      executive healthcare management member programs of the Association of University
      Programs of Health Administration. The results of the survey provide information
      about what is currently being taught in healthcare administration educational
      programs.

PMID- 11586659
TI  - Changing the health care system: a professional education program for Hispanic
      leaders in California.
AB  - This article reports characteristics and evaluation findings on a program aimed
      at promoting change in California's health care system by training minority
      managers and policy specialists. Between 1990 and 1992, 30 Hispanic college
      graduates enrolled in the University of Southern California's Hispanic Leadership
      Program. Funded in part by the W. K. Kellogg Foundation, this program led to
      award of the Master of Health Administration degree and involved students in a
      series of community workshops. Evaluation took place via alumni surveys and focus
      groups. Although four individuals failed to complete the program, nearly all
      others entered careers potentially leading to positions of influence in health
      care delivery. Graduates indicated that they possessed most of the skills they
      considered necessary to help improve services to Hispanic people. All had taken
      concrete action toward this objective. Experience with the program has provided
      lessons valuable for conducting efforts of this kind, the principal one being
      that success requires substantial human and material resources. Long-term follow
      up will be necessary to assess the program's ultimate impact on California's
      health care system.

PMID- 11586660
TI  - Constructive engagement: an integrative method of involving students in the
      learning process.
AB  - Providing a meaningful learning environment for each student represents a
      constant and ongoing challenge for faculty. This objective can be facilitated by
      active student participation in class interactions. The authors have developed
      the Constructive Engagement Method (CEM), an integrative method for actively
      involving students in the learning process. CEM permits students to hone
      interpersonal skills through the development of interrelated practical
      applications of critical listening and peer evaluation. The CEM approach
      introduces a method of student performance evaluation that has been judged as
      fair and equitable by almost all student participants. CEM fully involves all
      students, even in classes with very large enrollments. CEM as a teaching strategy
      utilizes a modified debate format that begins with a period of student
      preparation followed by a debate between two competing teams. The debate is
      followed by an evaluation period, during which the non-participating students
      practice the all-important task of determining the value of each team's
      investment in the process. CEM comprises five stages as follows: Phase 1-
      Preparation; Phase 2--Opening Statements; Phase 3--Intense Interaction; Phase 4-
      Closing Statements; and Phase 5--Evaluation. The CEM methodology has enjoyed
      strong support among graduate and undergraduate students.

PMID- 11586661
TI  - Building bridges between health management education and practice.

PMID- 11586662
TI  - The David A. Winston Health Policy Lecture. Health communication at Internet
      speed: recipe for disaster or better care?

PMID- 11586663
TI  - Trauma. Attack on the spirit.

PMID- 11586664
TI  - [Happy New Year 2001].

PMID- 11586665
TI  - [Gene therapy of ischemic heart disease. Growth factors and
      angiogenesis/arteriogenesis].

PMID- 11586667
TI  - [Cyclosporine treatment of patients with active ulcerative colitis refractory to
      high-dose glucocorticoid].
AB  - In around 30-40% of patients with acute severe ulcerative colitis the disease is
      refractory to treatment with high-dose glucocorticoids. Adding intravenous
      cyclosporine to the therapy in these patients has shown encouraging short-term
      results. Case notes of twenty-three acutely ill patients, who received
      intravenous cyclosporine during the period 1992 to 1998 due to failure of high
      dose glucocorticoid (n = 20) or due to medical complications (n = 3) which made
      surgery difficult, were reviewed. Eight patients had their first episode of
      ulcerative colitis whereas 15 had relapse or chronic active disease. Cyclosporine
      (4 mg/kg/dag) was added to glucocorticoid treatment after a median of 11 days.
      Clinical remission was achieved in 13 patients (57%) after a median of nine days,
      of these five subsequently underwent surgery. Ten did not obtain remission and
      went to surgery. Approximately a third of acutely ill ulcerative colitis patients
      refractory to standard treatment with high-dose glucocorticoids will benefit from
      intravenous cyclosporine in the longer term.

PMID- 11586666
TI  - [Therapeutic principles for chronic inflammatory bowel disease].
AB  - Whereas the incidence of ulcerative colitis has remained stable at around 8
      9/10(5), the incidence of Crohn's disease has increased from below 1 to more than
      5/10(5) per year during the last three decades. The new disease entities,
      collagenous colitis and lymphocytic colitis, are now covered by the term, chronic
      inflammatory bowel disease. The general principles of treatment of these diseases
      are to induce remission of outbreaks and to prevent outbreaks during remission.
      Available pharmaceutical products are 5-aminosalicylic acid preparations, with
      different delivery profiles in the gastrointestinal tract, glucocorticoids, and
      other immunosuppressants, especially azathioprine. New immunomodulating agents,
      with a specific effect on intracellular processes in the inflammatory cascade are
      now being developed, and infliximab, a TNF-alpha antibody, is now an accepted
      agent for use in severe, treatment-resistant cases of fistulising Crohn's
      disease. When medical treatment fails, surgical treatment is an option. In
      ulcerative colitis, colectomy is, in principle, curative, but it leaves the
      patient with either a permanent ileostomy or an ileal pouch, which serves as an
      artificial rectum after ileoanal anastomosis. This latter procedure has the
      obvious advantage of giving the patient a normal bowel continuity, but
      complications in the form of intractable "pouchitis" have been experienced in a
      small number of patients, thus necessitating removal of the pouch. Patients with
      Crohn's disease, who do not respond to medical treatment or present signs of
      stenosis in either the small or the large bowel, must be given surgical
      treatment, although an operation is less curative than in ulcerative colitis.
      Surgical resections for Crohn's disease must therefore be more conservative, so
      as to preserve the bowel and only remove macroscopically affected tissue.

PMID- 11586668
TI  - [Serious criminality among adolescents. I. Twenty years of mental observations of
      15-17 years old delinquents in greater Copenhagen].
AB  - The purpose of the study was to enlighten the background, psychopathology and
      criminality of young delinquents. Twenty years of reports for the court regarding
      young delinquents were analysed and information as to background, educational
      level, psychiatric diagnoses, criminal records and sentence was registered. Among
      91 delinquents aged 15-17 years, 65% had not completed primary school and 50%
      were unemployed. Eighty percent had committed violent acts (homicide or attempted
      homicide, robbery, violence, rape). Twenty-two percent were sentenced to
      psychiatric treatment, and more than 50% were imprisoned. In conclusion young
      delinquents have severe social problems and a disproportionally high number
      suffer from psychiatric illness. The main part of the adolescents are convicted
      to prison, in spite of young age, and at present no institutions in Denmark are
      suitable for the treatment of young delinquents with severe criminal records.

PMID- 11586669
TI  - [Serious criminality among adolescents. II. Criminality, psychiatric morbidity
      and mortality 15-20 years after the first mental observation].
AB  - The purpose of the present study was to enlighten the prognosis for young
      delinquents, who had been subject to a mental report for the court, regarding
      later psychiatric illness, mortality and criminal relapse. The study was
      retrospective based on register information about psychiatric admissions, death
      courses and later criminal commitments. After less than 20 years, 11% were found
      psychotic, 22% had died and 90% of the survivors had committed a total of 831
      criminal offences from drunk driving to homicide. We conclude, that at present no
      institutions in Denmark are suitable for the treatment of young delinquents with
      severe criminal records. Most of the young delinquents have psychological and
      behavioural disturbances from childhood, and early intervention is needed
      followed by careful documentation and follow-up studies in order to improve the
      prognosis for these young people.

PMID- 11586670
TI  - [Angiotensin-converting enzyme inhibitors after AMI].
AB  - The purpose of this study was to calculate the improvement in life expectancy by
      treating patients with left ventricular dysfunction after a myocardial infarction
      with an ACE inhibitor. Life expectancy was estimated as median lifetime and
      follow up in the TRACE study was prolonged until median lifetime could be
      calculated in both treatment groups. Median lifetime was reached in the placebo
      group after 4.6 years. In the trandolapril group median lifetime was increased by
      15.3 months or 27% (7-51%). We conclude that the increase in lifetime by
      treatment of patients with left ventricular dysfunction after a myocardial
      infarction is substantial.

PMID- 11586671
TI  - [Respiratory insufficiency caused by dapsone-induced methemoglobinemia].
AB  - We present a case of pneumonia and dapsone-induced methaemoglobinaemia.
      Methaemoglobinaemia leads to impaired delivery of oxygen to tissue. In our
      patient we observed that methaemoglobin interferes with the accuracy of pulse
      oximeter data. The patient was successfully treated with methylene blue, which
      converts methaemoglobin back to haemoglobin.

PMID- 11586672
TI  - [Late, life-threatening bleeding after hemorrhoidectomy].
AB  - Two patients with severe late rectal bleeding after haemorrhoidectomy are
      described. Both were suffering from alcohol-induced cirrhosis. The first patient
      died, because of a late diagnosis and treatment in combination with coagulation
      disturbances. We call attention to the difference between haemorrhoids and
      anorectal varices and also to the importance of keeping in mind the possibility
      of massive bleeding several days after haemorrhoidectomy.

PMID- 11586673
TI  - [Picture of the month: watermelon stomach].

PMID- 11586674
TI  - [Biological effects and mortality in connection with low dosage ionizing
      radiation].

PMID- 11586675
TI  - [A distinguished visit to Copenhagen].

PMID- 11586676
TI  - [Criteria concerning research support].

PMID- 11586677
TI  - [Research environment and research leadership].

PMID- 11586678
TI  - [Challenges of research leadership in hospitals].

PMID- 11586679
TI  - [The 5th edition of the Helsinki Declaration. Two significant changes concerning
      informed consent, one of these is not compatible with current Danish
      legislation].

PMID- 11586680
TI  - [Is bone mass regulated by a central mechanism?].

PMID- 11586681
TI  - [Albumin: an important principle in the treatment of decompensated liver
      disease].

PMID- 11586682
TI  - [Should "plant medicines" be withdrawn two weeks prior to surgery?].

PMID- 11586683
TI  - [The poor history of medicine].

PMID- 11586684
TI  - [Guidelines on antibiotics in the Laegeforeningens Medicinfortegnelse 2000].

PMID- 11586685
TI  - [A doubtful signal].

PMID- 11586686
TI  - [N-3 polyunsaturated fatty acids--for example Pikasol--in acute myocardial
      infarction].

PMID- 11586687
TI  - [2001: year 1 for the patient safety in Danish hospitals?].

PMID- 11586688
TI  - High flow oxygen installation. Special focus on a system for Leeds General
      Infirmary.

PMID- 11586689
TI  - Wythenshawe project completed. Special focus on a major PFI scheme finished on
      time and to budget.

PMID- 11586690
TI  - Clearing the air. A special examination of issues surrounding operating suite air
      flow systems.

PMID- 11586691
TI  - Reducing risk.

PMID- 11586692
TI  - More power to innovative engineers' elbows. When you get right down to it, what
      does sustainability really mean?

PMID- 11586693
TI  - Power quality management.

PMID- 11586695
TI  - In the blink of an eye.

PMID- 11586694
TI  - Switching on to better communications.

PMID- 11586696
TI  - [The unilateral space neglect in patients with arteriovenous malformations of the
      deep brain structures].
AB  - Clinical and neuropsychological study has been carried out in 187 patients with
      arteriovenous malformations (AVM) of the deep brain structures, including 28
      patients with caudate nucleus AVM, 35--with thalamus AVM, 45--with cingulated
      gyrus AVM, 43--with hippocampus AVM, 36--with corpus callosum AVM. Ignoring
      phenomenon in different modalities has been found in 47 patients, 40 patients
      having unfixed ignoring. The majority of the patients showed a left-side space
      and body ignoring and in 3 patients, with left-handedness signs, right-side
      ignoring has been observed. In all the patients ignoring development was
      associated with posthemorrhagic and postoperative impairment of the white matter
      (sensor conductor projections of sincipital and occipital lobes of
      periventricular white matter) or parietal and corpus callosum. In case of
      hemispheric local disturbances, ignoring developed in concomitant disorders
      (hemianopsia and hemihypesthesia) and coincided with them in modality. In case of
      corpus callosum damage, ignoring may develop without concomitant sensor disorders
      or may be on the other side (in case of simultaneous left hemisphere damage). The
      results obtained support the evidence for ignoring phenomenon independence.

PMID- 11586697
TI  - [Integral psychopathological model for impulse-control disorders in children,
      adolescents and young adults with schizophrenia].
AB  - Integral model for impulse-control disorders in schizophrenia is based on the
      data of examination of 200 patients who developed schizophrenia in childhood
      (14%) and adolescence (86%). The model comprises 4 components corresponding to
      the disorders variety. Phenomenological component (FC) reflects various
      pathological phenomena (sexual, eating, etc); typical psychopathological
      component (TPC) concerns mechanisms of their realization (impulsive, compulsive,
      obsessive, overvalued and transitional); processive component (PC) is represented
      by typical psychopathological traits comorbid with other psychopathological
      symptoms; evolutive component (EC) characterizes drive deviations, i.e. such
      manifestations that do not reach pathological level. FC stability allows
      considering it as a core in conventional space of the model, being surrounded by
      the other three components--TPC, PC, EC, thought to be marginal ones. Thus,
      impulse-control disorder dynamics in schizophrenia occurs due to change of its
      marginal components.

PMID- 11586698
TI  - [Diklovit relief of vertebrogenic and myofacial pain syndromes in lumbar space]].

PMID- 11586699
TI  - [Zolpidem (ivadal) treatment of sleep disorders].
AB  - The results of the multicenter study of zolpidem activity, being carried out in
      inpatient- and out-patient clinics of 20 cities in Russia, are reported. One
      thousand seventeen patients with transitory, short time and chronic dyssomnia
      have been included in the trial. Zolpidem (ivadal, "Sanofi-Syntelabo", France)
      has been prescribed once a day in a dose of 10 mg (one tablet) before going to
      sleep in a period of two weeks. The efficiency has been assessed by evaluating
      dyssomnia symptoms according to "Sleep assessment questionnaire" of "Sanofi
      Syntelabo" completed by the patients and "Clinical Global Impression Scale"
      completed by investigators. Safety has been assessed by analyzing a frequency of
      side effect appearance and changes in vital parameters: blood pressure, heart and
      breath rate. Zolpidem has been found to reveal high clinical efficiency and
      safety. By the end of the treatment, 59.5% of the patients experienced no
      difficulties in falling asleep, in 28.6% of the patients the latter being
      significantly reduced. On the whole the improvement was in 89.4% patients. No
      side effects have been observed. Zolpidem is a highly effective and safe
      medication for different type dyssomnia treatment that can be recommended for
      application in general clinical practice.

PMID- 11586700
TI  - [Acoustic brain stem evoked potentials in patients in patients with different
      forms of acute tick-borne encephalitis].
AB  - Acoustic brain stem evoked potentials (ABSEP) have been investigated in 90
      patients with different types of tick-borne encephalitis, in acute and remote
      stages. In all types of tick-borne encephalitis structural alterations mainly
      concerned II, III, IV and V complexes; changes of peak III, V latencies and
      interpeak I-III, I-V intervals have been detected as well. Focal type with
      multilevel CNS affection was distinguished by interpeak interval (III-V)
      elongation, higher per cent of abnormal III, V complexes and changes in wave
      amplitude V/I ratio. Stabilization of the peak latency and interpeak intervals in
      fever type occurred in 1-2 months, in meningeal type--in 2-3 months, in focal
      type--in 6-12 months. In several cases the ABSEP appearance preceded a focal type
      development, positive ABSEP dynamics was behind local neurological symptom
      regress. ABSEP method in acute tick-borne encephalitis allows predicting disease
      dynamics and outcome, conducting timely treatment correction and adequate
      rehabilitation, and substantiating optimal terms of out-patient clinical control
      in different types of the disease.

PMID- 11586701
TI  - [Transcranial doppler potentialities in asymptomatic "carotid disease"].
AB  - To elicit Transcranial doppler (TCD) potentialities in asymptomatic
      hemodynamically significant occlusive carotid diseases, twenty one patients with
      subclinical severe stenosis (more than 50%) of internal carotid artery (ICA) have
      been studied. After routine TCD, bilateral embolic monitoring of middle cerebral
      arteries (MCA) has been carried out. Besides, the functional test with breath
      holding for cerebrovascular reserve (CVR) was made in all the patients. Control
      group consisted of 18 healthy volunteers without any ICA abnormality. The results
      of the study reveal that CVR--the index of brain circulation autoregulation
      safety--is more exact marker of its stability than a degree of extracranial
      carotid stenosis. TCD embolic monitoring of MCA enables not only to diagnose
      brain embolism but to elicit the embolic source origin (arterio-arterial or
      cardial). Thus, both TCD with breath-holding and TCD embolic monitoring
      facilitate identification of patients at high risk of ischemic events, which is
      important for brain ischemic disease prophylaxis.

PMID- 11586702
TI  - [Immunogenetic cytokine restriction in multiple sclerosis].
AB  - Sixty eight patients with verified multiple sclerosis (MS) (mean EDSS score 3.1
      +/- 1.0) and 50 healthy donors have been investigated. Thirty five patients had
      relapsing-remitting, 25--secondary progressive, 8--primary progressive course.
      The remission was in 38, decompensation--in 20, relapse--in 10 patients.
      Lymphocyte subpopulations were investigated using monoclonal antibodies (Moscow)
      to the following antigens: CD3 (T-lymphocytes), CD4 (T-helpers), CD8 (T
      supressors), CD20 (8-lymphocytes), CD25 (IL-2 receptor), CD16 (natural killers),
      CD95 (activated cells ready to apoptosis). Cytokines and tumor necrosis factor
      alpha (TNF-alpha) levels were measured using ELISA test. HLA antigens were
      investigated by standard lymphocytotoxic test. In MS we found a fall of CD3, CD4,
      CD8, CD20 and CD16, but an increase of CD4/CD8, CD95, CD25. The CD95 level
      correlated with CD4, CD4/CD8 and CD16. In MS spontaneous IL-2, IL-6, IL-8 and TNF
      alpha production was raised and stimulated IL-6 and IL-8 secretion was reduced.
      IL-4, IL-6, IL-8, TNF-alpha and IL-1 beta serum production in vivo was elevated.
      We found an increase of CD3, CD4, CD16, CD25, but a decrease of IL-1 (p < 0.01)
      spontaneous production and IL-6, IL-8, TNF-a stimulated secretion in DR2(+) MS
      patients, comparing to DR2(-) patients and controls. In DR2(-) patients as
      compared to DR2(+) patients and controls, all lymphocyte subpopulations levels,
      especially CD8 (p < 0.001) one, were decreased, but spontaneous IL-8 (p < 0.01)
      production was increased. The data obtained indicate lymphocyte apoptosis
      activation, targeting promoted lymphocyte destruction, and suggest T helper type
      1 reaction prevalence in MS.

PMID- 11586703
TI  - [The modern model of medical and social care for the elderly].
AB  - From forty to seventy per cent of the elderly are reported to suffer from
      psychiatric disorders. Being prone to somatic and psychiatric comorbidity, aged
      people are also need for social care. This reason stipulates psychiatric care
      optimization and organizing a specialized service, providing care for the
      elderly. Service structure may be organized as following: (1) psychogeriatric
      units in psychiatric institutions; (2) psychogeriatric units in geriatric or
      general health care institutions; (3) psychiatric services and psychiatric
      facilities in social institutions. Each unit should comprise such kinds of care
      as day-hospital, in-patient clinic and out-patient clinic. Federal- and regional
      interdepartmental and interdisciplinary psychogeriatric centers may be
      established for elaboration of methodological and practical principles and
      coordination of geriatric, psychogeriatric and social care service's activity for
      providing care to the elderly.

PMID- 11586704
TI  - [Interleukin level in endogenous depression].
AB  - Interleukin level and mononuclear phagocytes (MPh) activity have been studied in
      19 patients with mono- and bipolar depression. All the patients were examined at
      admission to a hospital before treatment. The depression was characterized by low
      MPh activity, a significant (p < 0.05) fall in IL-1 beta production by stimulated
      monocytes, a trend to reduction of IL-2 production by stimulated lymphocytes,
      significant (p < 0.05) IL-2 serum concentration increase and significant (p =
      0.05) decrease of soluble IL-2 receptor (siL-2R) concentration in the serum.
      Significant positive correlation (r = 0.76; p < 0.05) between MPh activity and IL
      1 beta production has been found. Interleukin alterations were most manifest at
      the early disease stage (symptoms onset is less than one year). It is suggested
      that IL-2 accumulation in the blood serum in these patients is strongly
      influenced by a significant decrease of siL-2R serum concentration. MPh (the main
      IL-2 producers) activity reduction results in the monocyte IL-1 beta production
      decrease followed by changes in interleukin (in particular, IL-2) production by
      lymphocytes and other changes in interleukin system.

PMID- 11586705
TI  - [Hereditary neuromuscular diseases in the Samara region].
AB  - The paper presents the results of clinical-genealogic and electromyographic
      examination of 1157 patients with hereditary neuromuscular diseases from 689
      families. Based on the long-term genetic registry and application of the computer
      multi-dimensional mathematical analysis, the authors elaborated clinical
      electromyographic criteria for different forms of hereditary neuromuscular
      diseases by taking into account their etiologic heterogeneity. There were also
      general regularities and specific features of motor disorders indifferent
      clinical forms and at different stages of the pathological process. The findings
      are used by the Samara Medical-Genetic Center in its work.

PMID- 11586706
TI  - [Status and problems of mental health services in Armenia].

PMID- 11586707
TI  - [From the history of S. S. Korsakov psychiatric clinic].

PMID- 11586708
TI  - [Sensorimotor reactivity in children living in rural areas in post Chernobyl
      period].

PMID- 11586709
TI  - [Clinical genetics of multiple sclerosis].

PMID- 11586710
TI  - [Congress of neurologists from Russia and Great Britain].

PMID- 11586711
TI  - Comparison between thermoluminescence and electronic dosimetry results at the
      Belgian Nuclear Research Centre.
AB  - At the Belgian Nuclear Research Centre, SCK.CEN, the official dose of record is
      measured by thermoluminescence dosemeters (TLDs), read out on a monthly basis.
      The workers who frequently enter controlled areas also wear an electronic
      dosemeter (ED), in addition, as an ALARA tool. In this paper the dose values
      registered by both dosimetry systems during 1 year are compared. Special
      attention was given to the determination of the background radiation. The general
      agreement was good, although the TLD gave slightly higher values. An exercise
      like this yielded useful information on the storage and use of dosemeters by
      personnel and on the lowest limit of detection obtained with both systems.

PMID- 11586712
TI  - Comparison test of electronic dosemeters.
AB  - To assist with a planned purchase of electronic dosemeters by the Swiss Federal
      Office for Civil Protection, the calibration laboratory of the Paul Scherrer
      Institute performed tests on 11 types of electronic dosemeters manufactured by 10
      European and American companies. The technical specifications for the World Trade
      Organisation (WTO) tendering procedure were largely in accord with the
      specifications of the international standard IEC 61526. First tests were
      performed with samples from each type of dosemeter. The reproducibility of a dose
      of 0.1 mSv generated with 137Cs radiation at a dose rate of 2.1 mSv.h-1 was found
      adequate for all tested dosemeter types. The response for environmental levels of
      radiation showed a large variation, indicating insufficient background correction
      of some dosmeters. A very high dose rate of 10 Sv.h-1 provoked faulty dose
      readings for more than half of the tested dosemeters. Dosemeter response for low
      energy photon radiation was satisfactory for two of the tested dosemeter types.
      Four dosemeter types were selected for extended technical tests. Three samples of
      each of these dosemeter types were purchased. For drop and temperature tests the
      specifications of the WTO tendering procedure outranged the specifications of the
      IEC standard. Whereas even at a temperature of -25 degrees C the tested
      dosemeters functioned normally, drops from a height of 2 m onto a wooden surface
      rendered the samples of two dosemeter types inoperative.

PMID- 11586713
TI  - Quality assurance systems for individual monitoring services.
AB  - The International Basic Safety Standards for Protection Against Ionizing
      Radiation and for the Safety of Radiation Sources (BSS) require, inter alia, the
      establishment and implementation of quality assurance programmes to ensure that
      protection and safety requirements are met. The findings and conclusions of the
      International Conference on Topical Issues in Nuclear and Radiation Safety held
      in Vienna in 1998 includes, among others, the following recommendation concerning
      occupational radiation protection: The BSS require a quality assurance (QA)
      programme to be established as part of radiological protection. Extensive
      guidance for the development of a QA system is given in reports of ISO and IEC,
      but further guidance is needed on the interpretation and implementation of these
      standards. This paper is focused on the available international standards on
      quality assurance and on the work the IAEA is currently carrying out for their
      implementation in radiation monitoring services.

PMID- 11586714
TI  - Implementation of quality standards in an individual monitoring service.
AB  - In this paper the implementation of a quality system to the procedures of an
      individual monitoring service (IMS) is described from the practical perspective.
      The IMS of the Radiation and Nuclear Safety Authority (STUK) is used as an
      example. The IMS of STUK monitors about 8500 persons mainly working in hospitals,
      industry and research centres. The current thermoluminescence dosemeter (TLD)
      system was introduced in 1992 and the whole service changed to TLDs in 1995. The
      quality system compatible with the quality standards was introduced in 1999. An
      application for accreditation to fulfill EN45001 and ISO/IEC Guide 25 was made in
      December 1999, accreditation was achieved in August 2000 by the Finnish
      Accreditation Service (FINAS). The considerations needed for the quality system
      to fulfill the requirements of the quality standards are reported.

PMID- 11586715
TI  - Accreditation of a personal dosimetry service in Switzerland: practical
      experience and transition from EN 45004 to ISO 17025.
AB  - In compliance with the Swiss legislation on radiological protection, the Paul
      Scherrer Institute (PSI) operates a dosimetry service that is approved by the
      Swiss Federal Nuclear Safety Inspectorate. In 1997, the dosimetry service was
      also accredited by the Swiss Federal Office of Metrology and Accreditation as an
      inspection body for legal personal and environmental dosimetry, according to EN
      45004. The accreditation covers determination of personal dose equivalent for
      photon, neutron and beta radiation, and ambient dose equivalent for photon and
      neutron radiation, by means of thermoluminescence and solid state track detection
      techniques. Within this formal accreditation it was confirmed that the relevant
      requirements of ISO 9002 are also fulfilled. The first re-accreditation will take
      place in 2001 and work is going on to achieve the transition from EN 45004 to ISO
      17025. Accreditation is a feasible, practicable and acceptable way to achieve
      harmonisation in the field of dosimetry. However, before starting on the path to
      formal accreditation, a careful analysis should be made, taking into
      consideration not only cost-benefit aspects but also national legal requirements.

PMID- 11586716
TI  - Computerised glow curve analysis: a tool for routine thermoluminescence
      dosimetry.
AB  - The basic features of computerised glow curve analysis methods are presented,
      together with the advantages derived from their use for dosimetry. The rapid
      development of personal computers with progressively greater computation
      capability has permitted the application of different analysis methods for
      practical dosimetry. A very simple glow curve analysis method, specifically
      developed for the measurement of low or very low doses usually measured in
      personal and environmental dosimetry, is also discussed.

PMID- 11586717
TI  - A chamber for determining the conventionally true value of Hp(10) and H*(10)
      needed by calibration laboratories.
AB  - A secondary standard chamber for photon radiation developed for measuring
      directly the conventionally true value of the personal dose equivalent, Hp(10),
      in a slab phantom is now commercially available. In addition, this chamber can be
      used for determining the true value of the ambient dose equivalent, H*(10), in
      monodirectional radiation fields; for example, photon fields generated by X ray
      facilities. Once the chamber has been calibrated at the facility of the
      calibration laboratory, the true value of Hp(10) or H*(10) can be measured at
      other facilities without applying any conversion coefficients. For low energy
      photon fields the conversion coefficients are strongly dependent on the spectral
      distribution. For nominally the same radiation quality small spectral
      differences, caused, for example, by use of different X ray facilities, may lead
      to differences between the spectrum-averaged conversion coefficients from Ka to
      Hp(10) and H*(10), respectively, of up to several tens per cent. For this reason,
      tabulated conversion coefficients for low energy radiation fields cannot be used
      for calibration purposes, if the standard uncertainty is to be 2-5%. Direct
      measurement by the secondary standard chamber overcomes this problem.

PMID- 11586718
TI  - A new algorithm for identifying abnormal glow curves in thermoluminescence
      personal dosimetry.
AB  - In this paper an algorithm for the investigation of routine curves in
      thermoluminescence personal dosimetry is presented. In rare cases, the
      luminescence glow curves do not exhibit the expected form. They have an abnormal
      shape as a result of, for example, external contamination, hardware problems, and
      poor heat transfer. So, glow curves from a monthly exposure period are compared
      with regular glow curves. Each curve is divided into four regions of interest
      (ROIs) and the relationships between the different ROIs are analysed. There are
      few criteria combining all four ROIs, which are necessary to distinguish between
      normal and abnormal glow curves. For that, the numerical value and the channel of
      the curves maximum also need to be considered. In most cases an additional set of
      criteria permits the identification of the ROI in which the irregularity occurs.

PMID- 11586719
TI  - IAEA intercomparisons for individual monitoring of photon radiation 1987-1998.
AB  - In 1985 a technical committee set up by the IAEA formulated tasks to be performed
      in individual monitoring and recommended 'some type of personnel dosimetry
      activity'. Since 1987 several coordinated research projects have been performed
      within the Agency's Research Contract Programme concerning intercomparisons for
      individual monitoring. While the first intercomparison focused on the impact of
      the possible adoption of the new set of operational quantities introduced in ICRU
      Report 39 in 1985, later intercomparisons concentrated on the performance of
      personnel dosimetry services. In the last intercomparison, dosimetry services for
      nuclear power plants in IAEA Member States in Eastern Europe were given an
      opportunity to gain experience with the recommendations of the IAEA to use the
      operational quantity Hp(10). This paper analyses whether the important tasks
      formulated in 1985 were actually solved. It summarises the various
      intercomparisons carried out between 1987 and 1998 and highlights some results.

PMID- 11586720
TI  - A review of the properties of the dosimetric systems and the quality assurance
      programmes of 48 dosimetric services in the European Union and Switzerland.
AB  - This paper summarises the evaluation of the 1997 EURADOS questionnaire on
      dosimetric systems able to assess personal dose equivalent. In total, 56 approved
      dosimetric services in the European Union and Switzerland responded, together
      monitoring approximately 615,000 occupationally exposed persons. Of these
      services, 48 stated they were able to assess the external doses in terms of
      personal dose equivalent. The general aspects of the dosimetric systems and the
      quality assurance programmes of these services are discussed.

PMID- 11586721
TI  - EURADOS trial performance test for photon dosimetry.
AB  - Within the framework of the EURADOS Action entitled Harmonisation and Dosimetric
      Quality Assurance in Individual Monitoring for External Radiation, trial
      performance tests for whole-body and extremity personal dosemeters were carried
      out. Photon, beta and neutron dosemeters were considered. This paper summarises
      the results of the whole-body photon dosemeter test. Twenty-six dosimetry
      services from all EU Member States and Switzerland participated. Twelve different
      radiation fields were used to simulate various workplace irradiation fields. Dose
      values from 0.4 mSv to 80 mSv were chosen. From 312 single results, 26 fell
      outside the limits of the trumpet curve and 32 were outside the range 1/1.5 to
      1.5. Most outliers resulted from high energy R-F irradiations without electronic
      equilibrium. These fields are not routinely encountered by many of the
      participating dosimetry services. If the results for this field are excluded,
      most participating services satisfied the evaluation criteria.

PMID- 11586722
TI  - EURADOS trial performance test for neutron personal dosimetry.
AB  - This paper reports on the results of a neutron trial performance test sponsored
      by the European Commission and organised by EURADOS. As anticipated, neutron
      dosimetry results were very dependent on the dosemeter type and the dose
      calculation algorithm. Fast neutron fields were generally well measured, but
      particular problems were noted in the determination of intermediate energy fields
      and large incident angles, demonstrating the difficulties of neutron personal
      dosimetry. Of particular concern from a radiological protection point of view was
      the large number of results underestimating personal dose equivalent. A
      considerable over-response was noted in a few cases.

PMID- 11586723
TI  - IAEA Occupational Radiation Protection Programme.
AB  - The objective of the IAEA Occupational Protection Programme is to promote and
      assist in establishing an internationally harmonised approach for optimising
      occupational radiation protection. Guidance for IAEA Member States is provided
      through the hierarchical Safety Standards Series: Safety Fundamentals, Safety
      Requirements and Safety Guides. A set of three Safety Guides on occupational
      radiation protection has been published, jointly sponsored by the IAEA and the
      International Labour Office. Complementary advice, either topic specific or
      practice specific, is published as Safety Reports in other IAEA publications. In
      view of the technical difficulties associated with the introduction of the new
      radiation quantities for measurements and reporting, the IAEA assists its Member
      States by offering annual dosimetry intercomparisons. The purpose of this paper
      is to present the current and future IAEA activities in support of occupational
      radiation protection in the IAEA Member States.

PMID- 11586724
TI  - EURADOS trial performance test for personal dosemeters for external beta
      radiation.
AB  - On the initiative of the European Dosimetry Group (EURADOS) action group
      'Harmonisation and Dosimetric Quality Assurance in Individual Monitoring for
      External Radiation' a trial performance test for whole-body and extremity
      personal dosemeters broadly representative of those in use in the EU was
      accomplished. This paper deals with the part of the performance test concerned
      with exposure to beta radiation. Fifteen dosimetric services participated with
      whole-body dosemeters intended to measure beta doses (Hp(0.07)) of which 13 used
      thermoluminescent (TL) detectors and two used photographic films. Eight services
      participated with extremity dosemeters which all used TL detectors. A description
      is given of the irradiation set-up, the characteristics of the irradiation
      fields, the calibration quantity applied and the performance criteria used for
      the evaluation of the results. The paper discusses in detail the results obtained
      from the exercise. In particular, based on the replies to a questionnaire issued
      to each participant, the results are analysed in relation to important design
      characteristics of the dosemeters taking part in the test.

PMID- 11586725
TI  - Intercomparison measurements of extremity dosemeters in beta and/or photon
      radiation fields.
AB  - Beta dosimetry, especially at the extremities, is gaining in importance due to
      the increasing use of beta particle sources, e.g. in brachytherapy. The
      dosimetric properties of personal dosemeters to be worn on the extremities and
      capable of measuring the personal dose equivalent, Hp(0.07), in beta and/or
      photon radiation fields were investigated within the scope of intercomparison
      measurements organised by the PTB in two steps. The results were evaluated on the
      basis of recommendations from the German Commission on Radiological Protection
      (SSK). In the first step 10 types of dosemeter were investigated in beta particle
      fields in a range of mean energies from 0.06 MeV to 0.8 MeV. In the second step,
      five selected beta dosemeter types were exposed to beta particles and, in
      addition, to photons and to mixtures of both. Three dosemeters fulfill the
      requirements for the whole range of mean beta energy used for the intercomparison
      and meet the requirements for photon radiation from 8 keV to 662 keV.

PMID- 11586726
TI  - ENEA personal dosemeters for assessing Hp(10) and Hp(0.07).
AB  - Although, at present, neither Italian legislation nor technical protocols require
      that personal dosimetry is performed to assess Hp(d), the ENEA Individual
      Monitoring Service (IMS) is able to supply thermoluminescence (TL) whole-body and
      extremity dosemeters for photon and beta fields, based on LiF(Mg,Cu,P) detectors
      and these have been fully developed at the ENEA Institute for Radiation
      Protection (IRP). All irradiation tests have been performed with ISO phantoms and
      ISO recommended reference radiations at the ENEA-IRP Secondary Standard Dosimetry
      Laboratory. The whole-body dosemeter contains two LiF(Mg,Cu,P) (GR200) detectors
      that are filtered differently. One is filtered on both sides by 290 mg.cm-2 mass
      per area (270 mg.cm-2 Al + 20 mg.cm-2 plastic protective layer); the other is
      filtered on both sides by a plastic layer of 20 mg.cm-2 mass per area. In photon
      radiation fields, the maximum uncertainty due to the energy dependence of the
      response, is +/- 4% for Hp(0.07) in the energy range 13 keV to 202 keV, and +/-
      15% for Hp(10) in the range 13 keV to 1.25 MeV. The dosemeter response in terms
      of Hp(d,alpha) in beta fields has been investigated recently. The results of a
      EURADOS trial performance test for photon and beta fields are reported and
      discussed in this paper. The extremity dosemeter currently used at ENEA IMS
      consists of a GR200 detector glued on a kapton strip identified by a bar code.
      Its response in terms of Hp(0.07,alpha) has been measured recently and the
      results are given. Moreover, different dosemeter assemblies have been tested to
      compare the performances in photon and beta fields. Therefore, the following
      three constructions have been prepared: (1) an MCP-Ns (8.5 mg.cm-2 mass per area)
      detector with a Mylar filter of 0.5 mg.cm-2 mass per area; (2) a polyethylene
      filter of 12 mg.cm-2 mass per area; and (3) a GR200 (210 mg.cm-2 mass per area)
      detector with a Mylar filter of 0.5 mg.cm-2. Finally, a brief discussion on
      international and Italian requirements for personal monitoring is given.

PMID- 11586727
TI  - The NRPB PADC neutron personal dosimetry service.
AB  - The UK National Radiological Protection Board has been operating a successful
      contract neutron personal dosimetry service based on poly-allyl diglycol
      carbonate (PADC, also known by the trade name CR-39) since 1986, covering about
      1500 workers and serving major nuclear sites in the UK and abroad. In that time
      approximately 100,000 dosemeters have been issued. Since the service was
      launched, a number of aspects have undergone evolution and it is therefore
      worthwhile to give an updated summary of how the service operates and performs
      today. The description covers the choice of plastic and of etching technique, the
      design of the dosemeter, the features of the automated image analysis, and the
      characteristics of the control software. Also described are the approaches to
      calibration and traceability and to compensation for energy and angle dependence,
      with particular mention of the ability of the service to estimate the quantity
      Hp(10) in accordance with the requirements of the European Council Directive
      96/29/Euratom.

PMID- 11586728
TI  - Personal neutron dosimetry at a research reactor facility.
AB  - Individual neutron monitoring presents several difficulties due to the
      differences in energy response of the dosemeters. In the present study, an
      individual dosemeter (TLD) calibration approach is attempted for the personnel of
      a research reactor facility. The neutron energy response function of the
      dosemeter was derived using the MCNP code. The results were verified by
      measurements to three different neutron spectra and were found to be in good
      agreement. Three different calibration curves were defined for thermal,
      intermediate and fast neutrons. At the different working positions around the
      reactor, neutron spectra were defined using the Monte Carlo technique and ambient
      dose rate measurements were performed. An estimation of the neutrons energy is
      provided by the ratio of the different TLD pellets of each dosemeter in
      combination with the information concerning the worker's position; then the dose
      equivalent is deduced according to the appropriate calibration curve.

PMID- 11586729
TI  - Spanish intercomparisons for individual monitoring.
AB  - The Spanish Nuclear Safety Council (CSN) carries out an intercomparison programme
      for individual monitoring every 5 years. The objective is to acquire valuable
      information on the performance of the dosimetry systems of the participating
      Spanish approved dosimetry services and to assess precision and accuracy as
      quality indicators of overall dosimetry performance. CSN has carried out two
      intercomparison programmes, the last one in 1995, in which 18 approved dosimetry
      services participated. The dosemeters were exposed to photon fields (137Cs gamma
      rays and two X ray beams of different qualities), at two standard laboratories in
      Spain. The irradiations were done for evaluating personal dose equivalent,
      Hp(10), using the ICRU 47 phantom. Presently, CSN is carrying out a new
      intercomparison, which will be finished in 2001. Twenty-three dosimetry services
      will participate; 22 from Spain and one from Cuba. The irradiations will be done
      in reference photon radiation fields.

PMID- 11586730
TI  - From films to thermoluminescence dosemeters: the Greek Atomic Energy Commission
      experience.
AB  - The personnel dosimetry department of the Greek Atomic Energy Commission (GAEC)
      assures the individual monitoring of almost 8000 occupationally exposed workers.
      Thermoluminescence dosimetry systems will replace the existing photographic
      dosimetry system for the individual monitoring with the joint support of IAEA and
      GAEC. The thermoluminescence dosimetry system consists of two automated readers,
      one automated irradiator and about 20,000 dosemeters purchased from the Rados Co.
      The properties of two thermoluminescent materials have been compared: LiF has
      been chosen for the whole-body dosemeter configuration and Li2B4O7 for the
      extremities. The technical evaluation of the system has been performed according
      to the European and IEC standards. The overall uncertainty has been calculated.
      The existing database system, and the accounting and dispatching procedures have
      been adapted to the new demands. The system became operational on March 2000, and
      the official distribution of thermoluminescence dosemeters has begun.

PMID- 11586731
TI  - A thermoluminescence dosimetry system for personal monitoring in Ireland.
AB  - In 1993 the decision was taken to replace film badges with thermoluminescence
      dosemeters (TLDs) as the main form of dosemeter for both whole-body and extremity
      monitoring at the Dosimetry Service of the Radiological Protection Institute of
      Ireland (RPII) in Dublin. A review of commercially available automatic TLD
      systems was carried out to identify the system which best met the RPII's
      requirements. This paper describes the dosimetry system used, and, in addition,
      discusses the problems encountered and how these were addressed.

PMID- 11586732
TI  - Dose quantities in radiation protection and dosemeter calibration.
AB  - Dosimetric concepts and the definition of dose quantities for use in radiation
      protection were defined by the ICRP and the ICRU. Three types of quantities are
      of relevance for radiation protection purposes: basic physical quantities,
      protection quantities, and operational quantities. The physical quantities are
      universally accepted for the characterisation of radiation fields. These are
      defined in any point of the field, and the units are directly obtained by primary
      standards. The protection quantities form the basis for dose limitation. These
      quantities are not directly measurable. A set of measurable operational
      quantities provides, in general, a conservative estimate of the protection
      quantities. These operational quantities are recommended in routine monitoring of
      occupational exposure. The relation between these different types of quantities
      is discussed. In addition, the calibration procedure for dosemeters in terms of
      the operational quantities, including the use of calibration phantoms, is
      summarised.

PMID- 11586733
TI  - Mixed high energy photon and electron radiation fields for calibrating radiation
      protection dosemeters.
AB  - According to ISO 4037-3, calibrations of radiation protection dosemeters with
      photon radiation of energies above 3 MeV are performed under conditions of
      charged particle equilibrium. No information is provided concerning how to
      determine the response of dosemeters to radiation fields in the more general case
      when these conditions are not fulfilled. This paper deals with the production of
      mixed high energy photon and electron fields characterised by a lack or an excess
      of charged particles relative to conditions of equilibrium and describes a new
      procedure for the dosimetry in such fields. Through variation of the charged
      particle fluence fraction with respect to a nearly constant photon fluence,
      Hp(10) and H'(10) values varied by up to a factor of 1.74. The above mentioned
      basic study was utilised in the recent IAEA intercomparison (Co-ordinated
      Research Project 1996-1998) and EURADOS 'trial performance test' (1996-1998) for
      individual monitoring of photon radiation in testing response characteristics of
      individual dosemeters in non-charged particle equilibrium conditions.

PMID- 11586734
TI  - A method applicable to effective dose rate estimates for aircrew dosimetry.
AB  - The inclusion of cosmic radiation as occupational exposure under ICRP Publication
      60 and the European Union Council Directive 96/29/Euratom has highlighted the
      need to estimate the exposure of aircrew. According to a report of the Group of
      Experts established under the terms of Article 31 of the European Treaty, the
      individual estimates of dose for flights below 15 km may be done using an
      appropriate computer program. In order to calculate the radiation exposure at
      aircraft altitudes, calculations have been performed by means of the Monte Carlo
      transport code FLUKA. On the basis of the calculated results, a simple method is
      proposed for the individual evaluation of effective dose rate due to the galactic
      component of cosmic radiation as a function of latitude and altitude.

PMID- 11586735
TI  - Response of radiation protection dosemeters in mixed high-energy photon and
      electron radiation fields.
AB  - The response of radiation protection dosemeters in terms of the phantom-related
      operational quantities Hp(10) and H'(10.0 degrees) was measured for personal and
      area monitoring systems in mixed high-energy electron and photon radiation fields
      with energies up to 7 MeV. Using mixed radiation fields composed of different
      fractions of charged particle and photon fluence, three conditions were produced
      at the point of measurement: charged particle equilibrium (CPE) (a), a lack (b)
      and an excess (c) of charged particles relative to the conditions of CPE.
      Personal and area dosemeters of different types were investigated under
      conditions (a)-(c). A large variability of the response of the different
      dosemeter types was observed. The results are presented and discussed.

PMID- 11586736
TI  - A prototype personal neutron dosemeter with one silicon diode.
AB  - The performance of a personal neutron dosemeter with a single silicon diode using
      a linear combination of its pulse height information was studied. Its dosimetric
      behaviour in fields with neutrons of different energy and directional
      distribution is shown for neutron energies ranging from thermal to 100 MeV and
      for directions of incidence ranging from frontal to lateral. The dosemeter is
      photon-insensitive and its dose detection threshold is at about 20 microSv. The
      dosimetric characteristics are compared with those of commercial dosemeters based
      on silicon detectors.

PMID- 11586737
TI  - Comparison between direct ion storage and thermoluminescence dosimetry individual
      monitoring systems, and Internet reporting.
AB  - A new electronic direct ion storage (DIS) dosemeter allows accumulated personal
      dose equivalent Hp(d) at depths of 10 mm and 0.07 mm to be monitored in a few
      seconds by inserting the dosemeter into a local reader without deleting the
      accumulated dose. The DIS system meets general requirements on individual
      monitoring of hospital personnel using ionising radiation. It differs greatly
      from off-line thermoluminescence dosimetry systems and offers many additional
      benefits. The non-volatile reading takes only 5 s, is taken as often as needed,
      and the data are collected into a dose database, where background radiation is
      subtracted. Individual personnel doses are reported in Intranet as well as on the
      Internet at regular intervals to the National Regulatory Authorities.

PMID- 11586738
TI  - The dose-area product and assessment of the occupational dose in interventional
      radiology.
AB  - This study used dose-area product (DAP) data to determine the relationship
      between the dose received by radiologists and the DAP. The working conditions
      were simulated by phantom measurements. The doses of scattered radiation were
      measured using various scattering angles, distances and tube voltages. The
      calculated doses of scattered radiation were compared with the measured doses of
      scattered radiation. To test the validity of using such data for assessing
      occupational doses, the scatter dose on the radiologist or cardiologist was
      calculated from the DAP using the measured scatter factors. The dose to the
      lenses of the eyes may exceed the annual limit, and may therefore restrict the
      number of interventional procedures. A relation between the DAP and the
      occupational dose is difficult to establish, especially because staff doses are
      associated with the use of protective devices, positions of projections with
      respect to the patient, and working methods. However, the DAP may provide a good
      reference value for the dosimetric monitoring of staff.

PMID- 11586739
TI  - Retrospective dosimetry for Latvian workers at Chernobyl.
AB  - Between 1986 and 1991 approximately 6500 Latvian inhabitants were recruited for
      clean-up work at the Chernobyl nuclear power plant. Their absorbed doses are
      usually unknown, because less than half of them had their external exposure
      officially documented. Clinical investigations show a high morbidity rate for
      these clean-up workers when compared with that of the general population. In
      order to understand the causes of their diseases and the impact of ionising
      radiation, electron spin resonance (ESR) has been used to measure the absorbed
      doses in human tooth enamel. The doses estimated by ESR were between two and
      three times higher than previously documented and are in accord with the results
      of immunological and biological tests. The results may be explained by
      considering the effects of irradiation caused by long-lived incorporated
      radionuclides.

PMID- 11586740
TI  - The first operational dosemeter for neutrons which complies with IEC standard
      1323.
AB  - Individual neutron dosimetry represents one of the current difficulties in the
      field of radiological protection of workers. Since March 1999, the regulatory
      requirements in France for active (i.e. operational) dosimetry have been those of
      ICRP Publication 60, applicable from May 2000, necessitating the introduction of
      a new generation of neutron dosemeters. Over the last few years, the Institute
      for Nuclear Safety and Protection has been studying an individual electronic
      dosemeter for neutrons based on a semiconducting detector, capable of meeting the
      specifications laid down by a neutron dosimetry work group, including members
      from all the main players in the French nuclear industry. In 1998, the IPSN began
      transferring technology to the Saphymo company which, by the end of 2001, will be
      marketing Saphydose-n, the first individual dosemeter for neutrons which complies
      with IEC Standard 1323. This dosemeter is of compact design and can assess the
      individual dose equivalent Hp(10) in mixed neutron and gamma radiation fields. It
      wil be usable in any nuclear facility without prior knowledge of the average
      neutron spectrum or of the neutron-gamma ratio. It will be possible to connect
      the Saphydose-n dosemeter to any of the existing gamma deserter terminals to read
      the dose data and recharge the batteries.

PMID- 11586741
TI  - Study of the photon radiation performance of electronic personal dosemeters.
AB  - Following the specifications and test methods given by international standards
      IEC-61526 and ISO 4037, the dosimetry department of the IPSN studied the photon
      radiation performance of seven recent electronic personal dosemeters: The
      personal dosimetric performance of each piece of equipment was tested with X and
      gamma radiation between 12 keV and 1.25 MeV.

PMID- 11586742
TI  - Development of electronic personal neutron dosemeters: a European cooperation.
AB  - The European Commission recently sponsored an international research and
      development project, in which three 'active' personal neutron dosemeters were
      developed. Comparative irradiation experiments showed good results with respect
      to sensitivity and energy dependence of the response.

PMID- 11586743
TI  - Direct ion storage dosimetry systems for photon, beta and neutron radiation with
      instant readout capabilities.
AB  - The direct ion storage (DIS) dosemeter is a new type of electronic dosemeter from
      which the dose information for both Hp(10) and Hp(0.07) can be obtained instantly
      at the workplace by using an electronic reader unit. The number of readouts is
      unlimited and the stored information is not affected by the readout procedure.
      The accumulated dose can also be electronically reset by authorised personnel.
      The DIS dosemeter represents a potential alternative for replacing the existing
      film and thermoluminescence dosemeters (TLDs) used in occupational monitoring due
      to its ease of use and low operating costs. The standard version for normal
      photon and beta dosimetry, as well as a developmental version for neutron
      dosimetry, have been characterised in several field studies. Two new small size
      variations are also introduced, including a contactless readout device and a
      militarised version optimised for field use.

PMID- 11586744
TI  - Electronic neutron personal dosimetry with superheated drop detectors.
AB  - The prototype of an electronic personal neutron dosemeter based on superheated
      drop detectors is presented. This battery operated device comprises a neutron
      sensor, bubble-counting electronics and a temperature controller ensuring an
      optimal dose equivalent response. The neutron sensor is a 12 ml detector vial
      containing an emulsion of about 50,000 halocarbon-12 droplets of 100 microns
      diameter. The temperature controller is a low-power, solid-state device
      stabilising the emulsion at 31.5 degrees C by means of an etched foil heater. The
      microprocessor controlled counting electronics relies on a double piezo-electric
      transducer configuration to record bubble formation acoustically via a
      comparative pulse-shape analysis of ambient noise and detector signals. The
      performance of the dosemeter was analysed in terms of the requirements presently
      developed for neutron personal dosemeters. The detection threshold is about 1
      microSv, while the personal dose equivalent response to neutrons in the thermal
      to 62 MeV range falls within a factor 1.6 of 13 bubbles per microSv.

PMID- 11586745
TI  - An active personal neutron dosemeter based on microdosimetric principles: CIME.
AB  - Over the last few years IPSN has been developing a small, tissue equivalent
      proportional counter (TEPC) with multielement geometry for personal radiation
      protection monitoring. This paper presents the last prototype, which is
      insensitive to microphony, and the experimental results. Numerical modelling
      results using CERN codes are partly presented and allow an understanding of the
      nuclear and electrostatic physics involved in a TEPC.

PMID- 11586746
TI  - A prototype personal neutron dosemeter based on an ion chamber and direct ion
      storage.
AB  - Ionisation chambers are sensitive to both neutrons and photons. In order to
      produce a neutron dosemeter based on an ion chamber a double-chamber system which
      allows for differential readings has to be built. The system consists of one
      chamber with high neutron sensitivity (e.g. A-150 or polyethylene with 10B or 6Li
      compounds) and one chamber with low neutron sensitivity (e.g. graphite or
      Teflon). Different combined dosemeter prototypes were produced and their
      responses for standard photon and neutron radiation fields, as well as various
      field spectra, were determined. The feasibility of neutron dosimetry with ion
      chambers and direct ion storage (DIS) electronics has been proved. The results
      obtained with prototype dosemeters indicate the system's promising potential for
      legal approval in the future. Apart from dosimetric properties, the advantages of
      the system are its small size and weight, easy readout and relatively low
      production cost.

PMID- 11586747
TI  - Harmonisation and dosimetric quality assurance in individual monitoring for
      external radiation.
AB  - The current situation amongst Member States is that there are widely differing
      national requirements for dosimetric services and for dosemeter performance. It
      is clear that with the free movement of workers within the European Union (EU)
      and the requirements for individual dosimetry given in Council Directive 96/29
      EURATOM, a degree of harmonisation of requirements and procedures of EU Member
      States would be desirable. A EURADOS action group, made up of members from each
      of the EU Member States plus Switzerland, was set up with the overall objectives
      of consolidating within the EU the quality of individual monitoring using
      personal dosemeters and assisting movement towards harmonised procedures. An
      outline of the work of the action group is given and the term 'harmonisation' is
      discussed.

PMID- 11586748
TI  - Dose registry in Europe: national databases and international statistics.
AB  - This paper describes the approach used in ESOREX to compare national dose
      statistics of occupational radiation exposure at a European level. As every
      country uses its own scheme to characterise radiation work, the 'best common
      denominator' has to be found in order to compare dose statistics. The same
      problem has to be solved for the dose bands used in each country in order to
      scale dose distributions.

PMID- 11586749
TI  - The Spanish National Dose Registry and Spanish radiation passbooks.
AB  - The Spanish National Dose Registry (BDN) is the Nuclear Safety Council's (CSN)
      national database of occupational exposure to radiation. Each month BDN receives
      records of individual external doses from approved dosimetry services. The dose
      records include information regarding the occupational activities of exposed
      workers. The dose information and the statistical analysis prepared by the BDN
      are a useful tool for effective operational protection of occupationally exposed
      workers and a support for the CSN in the development and application of the ALARA
      principle. The Spanish radiation passbook was introduced in 1990 and since then
      CSN, as regulatory authority, has required that all outside workers entering
      controlled areas should have radiation passbooks. Nowadays, CSN has implemented
      improvements in the Spanish radiation passbooks, taking into account previous
      experience and Directive 96/29/EURATOM.

PMID- 11586750
TI  - European Study of Occupational Radiation Exposure (ESOREX).
AB  - The European Study of Occupational Radiation Exposure (ESOREX) project was
      initiated by the general directive EC DG XI and carried out by the Bundesamt fur
      Strahlenschutz, Germany (BfS). It consists of surveys carried out in the 28
      European states. The study provides comparable descriptions of the national
      administrative structures used to monitor and register individual occupational
      radiation exposure and the national dose statistics. It will establish the basis
      for identifying differences between the states and assessing the possibilities
      for European harmonisation.

PMID- 11586752
TI  - Occupational exposure in Portugal in 1999.
AB  - This study reports the occupational radiation doses for external exposure
      received in 1999 by the radiation workers monitored by the Radiological
      Protection and Nuclear Safety Department (DPRSN) in Portugal. Occupational
      exposures arise from conventional industry, research laboratories, the health or
      medical sector, and mining. There are no nuclear power plants in the country.
      There are two dosimetry systems running simultaneously at DPRSN, one based on
      film dosimetry and the other on thermoluminescence dosimetry (TLD). In 1999, 8400
      persons were monitored, 3100 with film and 5300 with TLD and the data presented
      in this report were obtained by using both technologies. The annual mean
      effective doses received from external radiation in the different fields of
      activity and the distribution of the annual effective dose by dose intervals are
      presented. The collective annual dose by field of activity is estimated and the
      contribution to the total annual collective dose is determined.

PMID- 11586751
TI  - Occupational exposures of nuclear power plant workers in Finland.
AB  - In Finland, the Radiation and Nuclear Safety Authority (STUK) maintains a central
      dose register where all occupational doses of radiation workers are recorded. The
      computerised register enables easy control of personal doses, including annual, 5
      year and lifetime doses. The type of radiation work is also recorded in the dose
      register. Finland was one of the first countries in the world to introduce dose
      limits based on the recommendations of ICRP 60. In this article, the radiation
      dose data of the Finnish nuclear power plant workers are analysed. The majority
      of the radiation doses are received during the maintenance outages. The trend of
      the 5 year doses and their distribution are presented. Doses received during
      different work assignments were averaged over the years 1996-1999 and they are
      also discussed in this article.

PMID- 11586753
TI  - Development of a quality assurance programme for external personal dosimetry in
      Slovenia.
AB  - In order to improve the quality of individual monitoring and to achieve
      harmonisation with the new international standards, important components of a
      quality assurance system are considered and are presented as a result of
      cooperation of different institutions. The components are quality assurance and
      routine quality control of monitoring systems, and the creation of a central
      state dose register of workers.

PMID- 11586754
TI  - Analysis of whole-body doses received by occupationally exposed workers in
      Ireland (1996-1999).
AB  - The work described in this paper is based on the results of routine whole-body
      measurements carried out by the Radiological Protection Institute of Ireland
      Dosimetry Service from 1996 to 1999. Data on the occupational radiation exposures
      of monitored personnel are examined and have been found to follow the skewed
      distribution reported by UNSCEAR. The annual average effective dose for each
      major work practice over the 4 years is given and compared with the UNSCEAR
      reference value of 1.1 mSv per year for all occupations. Evidence suggests that
      improvements in procedures and the use of better equipment have resulted in a
      reduction in the numbers of workers receiving measurable doses.

PMID- 11586755
TI  - Current status of personal dosimetry in industry, research and medicine in
      Lithuania.
AB  - The personal dosimetry service of the Radiation Protection Centre performs
      individual monitoring for all the industrial, medical and research radiation
      workers. The RADOS and DTU TLD systems are used for monitoring of doses. The DTU
      TLD system is used for measurements of doses to extremities and for measurements
      of public external exposure. Finger ring TLDs are used in therapy which uses
      radiopharmaceuticals. The RADOS system is also used for evaluation of patients'
      doses in selected hospitals. The dosimetry service recently provided individual
      monitoring of approximately 3000 workers. The average occupational dose was about
      1.06 mSv for medical workers and 3.2 mSv for industrial radiography workers in
      1999. Detailed analysis of doses received by different categories of workers is
      performed. A system for the urgent review of work conditions in the case of
      increased dose has been set up.

PMID- 11586756
TI  - Occupational exposure to external ionising radiation in Poland, 1999.
AB  - In 1999 about 6208 radiation workers from 389 departments were monitored by CLOR
      in Poland. The distribution of annual personal doses shows that 85% of controlled
      workers received doses below the MDL (0.4 mSv) and about 97% controlled workers
      received doses below 5 mSv. Doses higher than 50 mSv were received by three
      operators of industrial radiography units. The radiation workers under control
      are divided into four main work sectors: nuclear industry, research and
      education, medicine, and general industry. The average annual dose for all
      workers in each particular sector was 0.22 mSv, 0.22 mSv, 0.30 mSv and 0.80 mSv,
      respectively. The average annual dose for the entire monitored population was
      0.47 mSv. The average annual dose in each particular sector for number of workers
      receiving E > 0, i.e. Hp(10) > or = 0.4 mSv, amounted to 1.78 mSv, 2.03 mSv, 1.88
      mSv and 4.85 mSv, respectively. The average annual dose for the full number of
      workers receiving E > 0 was 3.21 mSv. This paper contains the detailed analysis
      of occupational exposure. The distributions of annual occupational exposure in
      different work sectors are also given.

PMID- 11586757
TI  - The system of personal monitoring and the evaluation of occupational exposure in
      the Czech Republic.
AB  - New legislation concerning radiation protection, which was effective in the Czech
      Republic from 1997, followed from the recommendations of ICRP Publication 60 and
      the IAEA BSS, and included all new basic principles for the protection of
      radiation workers given in these documents. The requirements for the personal
      monitoring of category A workers and the recognition of the capacity of dosimetry
      services were identified as being very significant for radiation practice, and
      will be licensed by the State Office for Nuclear Safety (SONS). The license
      application will include the methodology of effective dose evaluation, the
      description of QA and QC of the service, the system of customer communication and
      dose recording and reporting. In accordance with legislation requirements, the
      licensee is obliged to report the personal and dosimetry data of category A
      radiation workers to SONS. For the purpose of data collection, SONS is developing
      the central registration system of occupational radiation exposure (CROE).
      Personal monitoring is managed for about 20,000 workers in 1500 workplaces. The
      paper describes in detail all current aspects of external monitoring of workers
      in the Czech Republic.

PMID- 11586758
TI  - Dosimetric performance requirements for the routine dose assessment of external
      radiation.
AB  - Dosimetric performance requirements must take the following into consideration:
      general radiation protection requirements established by the International
      Commission on Radiological Protection (ICRP), workplace conditions prevailing
      during (routine) work, and technical requirements set by international or
      national bodies. For performance tests the general requirements on the precision
      of dose measurements can be represented by the 'trumpet curves'. For photon
      radiation several measurements of the workplace conditions are reported. The main
      conclusions drawn from these measurements are the following: the photon energy
      range from 20 keV to 2 MeV, or even 7 MeV, is of importance for individual
      monitoring. The range of directions of radiation incidence on the dosemeter is
      very large, nearly the frontal hemisphere or even rotating, and almost all
      spectra are broad with respect to energy. In view of the great variety of
      workplace conditions, the scope of most of the technical requirements is not
      sufficiently great. No technical requirement is at present fully in accordance
      with the general principles of an uncertainty analysis.

PMID- 11586759
TI  - Present status of approval procedures in the EU member states and Switzerland.
AB  - The European Union Council Directive 96/29/EURATOM requires that 'individual
      monitoring shall be ... based on individual measurements which are established by
      an approved dosimetric service' and that 'Each Member State shall make
      arrangements to recognise, as appropriate, the capacity of ... approved
      dosimetric services'. At present, approval of dosimetric services does not have
      the same meaning within EU Member States and Switzerland. In some countries,
      service and dosemeter approval is clearly separated, in some others only one of
      the two is supposed to be tested, and in others no approval is required.
      Dosimetric requirements and criteria are based on different international
      documents (e.g. IEC, ISO, ANSI, CEC report) or national specific rules. Approval
      frequency can be once, every 2 or more years. Approval can be based on either
      evaluation of technical and management reports, irradiation tests, inspection on
      site or the three steps together. In most cases, approval involves photon
      dosimetry while beta and neutron dosimetry test procedures are not as well
      established. However, comparisons may lead to some convergent evolution of
      procedures and to a greater degree of harmonisation and quality consolidation.

PMID- 11586760
TI  - Regulatory approval of a dosimetry service using electronic dosemeters for
      individual dose measurements in the UK.
AB  - In the United Kingdom it is a legal requirement that the radiation doses received
      by classified persons are measured using dosemeters that have been provided by an
      approved dosimetry service. The Health and Safety Executive (HSE) is the
      regulatory body responsible for approving these dosimetry services. Until
      recently, statutory dose measurements in the UK have been made with well
      established dosimetry techniques involving the use of film or TLDs. In January
      2000 HSE granted approval to a dosimetry service, operated by a UK nuclear
      utility, to provide a service to nuclear sites for making measurements of
      individual dose using electronic dosemeters. HSE has published the requirements
      that prospective dosimetry services must satisfy in order to gain regulatory
      approval. These requirements are applicable to those services wishing to use
      established techniques with film and TLDs and also to services that wish to use
      novel systems of dose measurement such as electronic dosemeters. This paper
      briefly describes the regulatory framework for the approval of dosimetry services
      in the UK, the criteria used by HSE for the approval of these services with
      particular reference to electronic dosemeters, and the regulatory issues
      associated with the use of electronic dosemeters for statutory individual dose
      measurements in the UK.

PMID- 11586761
TI  - The outlook for the application of electronic dosemeters as legal dosimetry.
AB  - This study analyses new trends of a set of 12 electronic personal dosemeters in
      order to gain an overview of their main advantages and limitations. Physical
      characteristics and radiological, mechanical and environmental performance were
      tested according to IEC-61526 Standard requirements. The study highlights the
      different behaviour of the selected dosemeters. In particular, it is demonstrated
      that three of the tested devices fulfilled most of the established requirements,
      whereas another three of them presented important faults. The parameters that
      need more development are, in general, the response at low energy photon and beta
      radiation, and the dose rate alarm features. In some cases, mechanical problems
      as well as interference in the response due to external electromagnetic fields
      were also found. However, the results of the study foresee a promising future for
      the application of the newest personal electronic dosemeters as legal personal
      dosemeters and show the need for internationally agreed technical requirements
      within the European countries.

PMID- 11586762
TI  - Harmonised dosimetry services, and new measuring techniques: a challenge ahead.

PMID- 11586763
TI  - Implementing new recommendations for calibrating personal dosemeters.
AB  - This paper analyses the differences between the calibration procedures for
      personal dosemeters recommended by ICRU 47 and ISO 4037-3. The tissue equivalence
      of the PMMA and the ISO water slab phantoms are analysed by means of the Penelope
      Monte Carlo code for monoenergetic and filtered X ray photon beams and compared
      with the results of two other independent codes. The influence of the calibration
      method is also verified experimentally, both on a thermoluminescence and an
      electronic personal dosemeter. Good consistency between both calibration
      procedures is shown provided that a correction factor for backscatter differences
      between the PMMA and the ICRU phantom is introduced. The Monte Carlo simulation
      is used to determine this correction to a greater accuracy.

PMID- 11586764
TI  - Performance testing of personal dosemeters from eleven dosimetry services in
      Sweden.
AB  - The Swedish regulation, SSI FS 98:5, requires that radiological workers of
      category A use dosemeters from an approved personal dosimetry service. The 11
      services operating in Sweden at the moment use five different types of dosemeter.
      All have been tested for their ability to determine Hp(10) and some of them to
      determine Hp(0.07) according to the European Commission report Radiation
      Protection 73, EUR 14852, of 1994. The five unique systems have been tested
      regarding the angular and energy dependence of the response of the dosemeters.
      The test points for the determination of Hp(10) are all, except one, within the
      trumpet curve and for the unique systems it is shown that the uncertainty related
      to angular response at three different energies is within the required +/- 40%
      except for the lowest X ray quality 40 kV. The energy dependence dominates over
      the directional dependence and the choice of radiation quality for calibration is
      of great importance for the system performance.

PMID- 11586765
TI  - Nondestructive indices of trace element exposure in squamate reptiles.
AB  - Compared with birds, mammals, fish, and even amphibians, very little is known
      about the effects of contaminants on reptiles. Recent evidence that many reptile
      populations may be declining has stimulated demand for toxicological studies of
      reptiles as well as development of nondestructive sampling techniques useful for
      assessing and monitoring contaminant exposure. The current study experimentally
      evaluated the utility of shed skins, tail clips, and blood samples as
      nondestructive indices of trace element exposure in banded water snakes, Nerodia
      fasciata. For 13.5 months, snakes were either fed fish from a coal ash
      contaminated site or uncontaminated food from a reference site. Snakes fed
      contaminated prey accumulated As, Cd, Se, Sr, and V in various organs (i.e.
      liver, kidney, and/or gonads). Moreover, non-parametric discriminant function
      analysis revealed that snakes could be placed in two groups that reliably
      reflected their experimental diet based upon Se, Sr, and As concentrations in
      tail clips, blood, and/or shed skins. We suggest that nondestructive sampling
      techniques, particularly analyses of blood and tail clips, may be easily applied
      in evaluations of contaminant exposure in the field and laboratory and may
      prevent excessive destructive sampling of potentially threatened reptile species.

PMID- 11586766
TI  - Comparative studies on the biokinetics of Cd, Cr, and Zn in the green mussel
      Perna viridis and the Manila clam Ruditapes philippinarum.
AB  - A kinetic approach was employed to determine the rates of metal uptake (Cd, Cr
      and Zn) from the dissolved phase and the rate constants of metal depuration in
      the mussel Perna viridis and the clam Ruditapes philippinarum. The effects of
      ambient metal concentration, salinity, and body size on the metal influx rate
      were examined. A linear positive relationship was observed between the metal
      influx rate and the metal concentration in ambient seawater. There was some
      evidence that Zn uptake was regulated by the bivalves in response to an increase
      in ambient Zn concentration. The uptake rate constant was highest for Zn and
      lowest for Cr in both bivalves, and was higher in mussels than in clams. The
      metal influx rate decreased by 1.6-1.8 times for the three metals when the
      salinity was increased from 15 ppt to 30 ppt. However, the effect of salinity on
      Zn influx in mussels was not statistically significant. A negative relationship
      of Cd and Zn influx rates with tissue dry weight was also found in both bivalves.
      Cr uptake in mussels was not significantly correlated with body size, but its
      uptake in clams was significantly correlated with body size. Metal concentration
      in ambient seawater appeared to be the most determining factor on metal uptake
      from the dissolved phase in both bivalves. The efflux rate constants of the three
      metals were within the range of 0.01-0.03 d-1, and were comparable between the
      mussels and the clams. Using a simple bioenergetic-based kinetic model, it was
      shown that both dissolved uptake and food ingestion can contribute to metal
      accumulation in the bivalves. However, Zn accumulation in the clam R.
      philippinarum was dominated by uptake from food ingestion. Metal partitioning in
      ingested food was found to be critical in affecting the relative importance of
      metal uptake from the dissolved phase and food source, primarily because of the
      large variability of this parameter in natural environments.

PMID- 11586767
TI  - Lysosomal and lipid alterations in the digestive gland of mussels, Mytilus
      galloprovincialis (L.) as biomarkers of environmental stress.
AB  - Lysosomal and lipid alterations in the digestive gland cells of the common mussel
      Mytilus galloprovincialis collected from six stations along Thermaikos Gulf
      (Northern Greece) were monitored through a 1-year period. The ultrastructural
      observations of the digestive cells of sampled mussels indicated a higher
      incidence of "granular" or "dark" residual bodies in the relatively more polluted
      stations compared to less polluted ones. Alterations in the lysosomal system of
      digestive cells were assessed: (1) using the lysosomal membrane stability test
      (2) quantifying lysosomal structural alterations of the residual bodies and the
      heterolysosomes of the digestive cells at the ultrastructural level, and (3)
      determining the elemental composition of lysosomes by means of X-ray
      microanalysis on epoxy resin sections. Evaluation of neutral lipids was realized
      using image analysis on histochemical resin sections. Mussels from the most
      heavily polluted stations exhibited reduced lysosomal membrane stability, higher
      volume density and diameter of heterolysosomes and residual bodies, and, in some
      cases, relatively higher lysosomal heavy metal content compared to mussels from
      less polluted stations. The results showed that the lysosomal membrane stability
      and the volume density of the residual bodies are more sensitive to general
      stress compared to the other biomarkers used, and could be used successfully as
      early warning tools in biomonitoring programs.

PMID- 11586768
TI  - Assessment of air pollution in Nagasaki City: determination of polycyclic
      aromatic hydrocarbons and their nitrated derivatives, and some metals.
AB  - Air pollutants such as polycyclic aromatic hydrocarbons (PAHs), their nitrated
      derivatives (NPAHs), and some metals on airborne particles in Nagasaki city,
      Japan were determined over a period of 12 months by high-performance liquid
      chromatography with chemiluminescence, fluorescence and flameless atomic
      absorption spectrometry. The average concentrations (range) were 18.24 (4.07
      41.54) ng/m3 for total PAHs, 0.91 (0.23-4.10) pg/m3 for NPAHs, 7.95 (1.71-16.31)
      ng/m3 for Pb, 11.56 (3.35-24.96) ng/m3 for Mn and 3.79 (0.97-14.71) ng/m3 for Ni
      (n = 136). The toxic equivalency factors adjusted concentration of total PAHs
      determined in Nagasaki city area was 2.33 ng/m3. Concentrations of total PAHs and
      NPAHs in winter were higher than those in summer. In a weekly variations study,
      total PAHs and NPAHs concentrations, as well as traffic volume showed a similar
      tendency with all values higher during weekdays and lower at the weekend. The
      correlation coefficients between total PAHs or NPAHs and traffic volume were
      0.781 and 0.818, respectively. These results suggested that one of the main
      sources for NPAHs and PAHs in a city area might be motor vehicles.

PMID- 11586769
TI  - Cd and Zn concentrations in small mammals and willow leaves on disposal
      facilities for dredged material.
AB  - Disposal sites for dredged material are often polluted with heavy metals. The
      uptake of Cd and Zn by small mammals and willow trees was assessed on three sites
      with a different pollution degree. Detailed soil sampling showed a huge variation
      in soil characteristics within the sites, typical for disposal sites for dredged
      material. This variation made risk assessment and interpretation of soil chemical
      analyses complicated. Small mammals were thought to give a more integral
      description of the contaminant level because they cover a large area. Cd
      concentrations in small mammals were elevated compared with background levels
      whereas Zn concentrations were rather low. There were no significant differences
      between sites in Cd or Zn levels in animals. Leaf analysis showed a clear
      response to the pollution degree of the sites. The calculations using the BIOMAG
      model indicated that the Cd of the soil caused low risk for predators. However,
      the elevated Cd and Zn concentrations in the willow leaves on the polluted sites
      and the high Cd concentrations in the small mammals on all sites indicated that
      ecosystem development should be carefully considered.

PMID- 11586770
TI  - A field study on EROD activity and quantitative hepatocytological changes in an
      immature demersal fish.
AB  - Demersal fish, Solea ovata, were sampled from a reference site and a site where
      highly contaminated sediment is dumped. Sexually immature fish from the
      contaminated site exhibited significantly higher EROD activity compared with
      counterparts sampled from the reference site. No significant difference in EROD
      activity could be found for sexually mature males and females between sites. The
      relationship between EROD activity and quantitative changes in hepatic
      lipofuscin/ceroid, as well as peroxisome, was investigated for immature S. ovata.
      A significant correlation was found between EROD activity and volume density of
      lipofuscin/ceroid in fish hepatocyte (r = 0.750; P < 0.05), but no significant
      correlation was discernible between EROD activity and peroxisomes. Results from
      this field study corroborate our earlier laboratory findings, in which induction
      of EROD activity by intraperitoneal injection of benzo[a]pyrene was associated
      with increase in absolute volume and absolute number of lipofuscin/ceroid in
      hepatocytes. The present study provides further evidence that induction of EROD
      activity is associated with an increase in hepatic lipofuscin/ceroid and possibly
      cytological damages in immature S. ovata. This cytological change may serve as a
      potential marker for exposure to PAHs and PCBs.

PMID- 11586771
TI  - Heavy metal solubility in podzolic soils exposed to the alkalizing effect of air
      pollutants.
AB  - The heavy metal content of pine forest soil was studied near the boundary between
      Russia and Estonia, an area characterized by large amounts of acidic and basic
      air pollutants, mainly sulfur dioxide and calcium. Alkalization dominates the
      processes in soil, since sulfur is adsorbed only in small quantities, and calcium
      is much better adsorbed. In addition to Ca, great amounts of Al, Fe, K, and Mg
      are accumulated in the humus layer due to air pollution. The heavy metal content
      has increased. The exchangeable content of heavy metals was in many cases much
      higher in polluted alkaline soils than in non-polluted acidic soils, even the
      ratio of exchangeable to total metal content being higher in alkaline plots. To
      avoid a dangerous increase in soluble heavy metal content, it is important to
      decrease not only the large sulfur emissions of local pollutant sources, but also
      the alkaline pollutants. A similar concern must be taken into account when liming
      of acidic forest soils is planned.

PMID- 11586772
TI  - Genotoxic damage in free-living Algerian mouse (Mus spretus) after the Coto
      Donana ecological disaster.
AB  - The Donana National Park (Spain), one of the most important wildlife sites in the
      West of Europe, was affected (25 April 1998) by the spill of acidic waste rich in
      toxic metals (mainly zinc, lead, copper, etc.), arsenic and aromatic amines from
      the Aznalcollar mine accident. Micronuclei test with May Grunwald-Giemsa and with
      CREST-antikinetocore staining using DAPI as counter-staining were performed on
      peripheral blood erythrocytes from Algerian mice to evaluate genotoxic damage.
      Animals were collected in four locations each differently affected by the
      disaster. Higher frequencies of micronuclei and CREST-positive micronuclei were
      observed in the sites, which were reached by toxic sludge and contaminated water
      in comparison with those located within the park. The results obtained applying
      the two methods indicate that DAPI staining is more sensitive in detecting
      micronuclei. Genotoxic biomonitoring should be further carried out in the area to
      control the mutagenetic level in natural populations.

PMID- 11586774
TI  - Gross fluxes and estuarine behaviour of pesticides in the Scheldt estuary (1995
      1997).
AB  - As part of the Fluxes of Agrochemicals into the Marine Environment (FAME)
      project, the gross fluxes of selected pesticides (i.e. the herbicides atrazine,
      simazine, alachlor and metolachlor, the atrazine degradation product
      desethylatrazine, the insecticide dichlorvos and the antifouling agent Irgarol
      1051) transported by the river Scheldt and the Canal Ghent-Terneuzen were
      determined from March 1995 through February 1997. In general, the observed
      temporal trends were related to the application period of the pesticides, except
      for metolachlor for which elevated concentrations were observed in the winter of
      1995-1996. Relatively large gross fluxes were found for desethylatrazine compared
      with its parent compound. A study on the estuarine behaviour of pesticides showed
      distinct differences between the compound classes. The mixing plots of the
      organophosphorus insecticides dichlorvos and diazinon revealed clear evidence of
      estuarine loss processes which agrees with their low DT50 values reported for
      water/sediment systems, their relatively high Henry's law constants and, for
      diazinon, its relatively high Koc value. The mixing plots of the acetanilides
      alachlor and metolachlor were strongly influenced by an additional direct
      emission into the estuary, which was evident from a maximum in dissolved
      concentration near a salinity of 10@1000. An apparent conservative behaviour was
      observed for the triazine compounds atrazine and Irgarol 1051. This was in
      contrast to simazine, which showed an apparent non-conservative behaviour.
      However, the time profiles of the riverine concentrations of simazine did not
      exclude that the observed curvature was solely caused by estuarine losses;
      therefore, additional modelling is required. In a follow-up study a suitable
      hydrological model of the Scheldt estuary was constructed; the results will be
      presented in a forthcoming paper (Steen, R.J.C.A., Evers, E.H.G., Van Hattum, B.,
      Cofino, W.P. and Brinkman, U.A.Th. Net fluxes of pesticides from the Scheldt
      estuary into the North Sea: a model approach. Environmental Pollution, submitted.

PMID- 11586773
TI  - Multiple effects of chromate on the photosynthetic apparatus of Spirodela
      polyrhiza as probed by OJIP chlorophyll a fluorescence measurements.
AB  - Chromate (Cr) decreases the growth of Spirodela polyrhiza. The fronds lost their
      pigments. The O2 evolution was also decreased. The Cr effect was found to be dose
      dependent. The toxic effects of Cr have further been studied on the
      photosynthetic activity of Spirodela polyrhiza by means of the chlorophyll a (Chl
      a) fluorescence transient O-J-I-P. The Chl a fluorescence transients were
      recorded in vivo with high time resolution and analyzed according to the JIP-test
      which can quantify the photosystem II behavior. Cr treated plants show a decrease
      in yield for primary photochemistry, phi Po. The performance index of PSII,
      PIABS, which is the combination of the indexes of three independent parameters,
      (1) the total number of active reaction centers per absorption (RC/ABS), (2)
      yield of primary photochemistry (phi Po) and (3) efficiency with which a trapped
      exciton can move an electron into the electron transport chain (psi 0), decreased
      due to Cr treatment. Chromate sensitivity varies within plant populations. In
      summary Cr affects several targets of PSII. More specifically, the main targets
      of Cr, according to the JIP-test, can be listed as a decrease in the number of
      active reaction centers and damage to the oxygen-evolving complex.

PMID- 11586775
TI  - Occurrence of butyltin compounds in the waters of selected lakes, rivers and
      coastal environments from China.
AB  - The presence of butyltin compounds was investigated for the first time in
      selected lakes, rivers and coastal environments of China. Aqueous samples were
      pretreated by the technique of headspace solid phase micro-extraction after
      hydride generation with sodium tetrahydroborate (NaBH4). Quantitative measurement
      of tributyltin (TBT), dibutyltin (DBT) and monobutyltin (MBT) concentrations were
      accomplished by capillary gas chromatography with flame photometric detector
      using quartz surface-induced luminescence. Experimental data demonstrated the
      widespread occurrence of butyltin compounds in the Chinese aquatic environment.
      In some locations, the concentrations of TBT were higher than the acute and
      chronic toxicity threshold of sensitive fresh water or marine organisms. Although
      DBT and MBT (which mainly come from the degradation of TBT), are less toxic,
      their occurrence can still affect the ecosystem over a long time frame.

PMID- 11586776
TI  - The use of sediment analogues to study the uptake of pollutants by chironomid
      larvae.
AB  - A technique is described that uses artificial resin beads with known surface
      properties to investigate the factors influencing the bioaccumulation of
      pollutants from sediments. One advantage of this technique is that it provides a
      standard procedure against which it is possible to calibrate natural sediments
      with their diverse properties. The method has been used on third instar larvae of
      the midge Chironomus riparius and the results are compared with previous studies
      on the worm Lumbriculus variegatus. The use of a standard test using resin beads
      as a substitute for natural sediment allows comparisons to be made between
      species and substrates. Thus, the bioaccumulation factors for the midge larvae
      are much smaller than those of the worm and this correlates with the ability of
      the insect larva to detoxify many pollutants. It is also possible to use the test
      to identify if ingestion of the sediment increases the bioaccumulation of
      contaminants and whether this involves the release of pollutants by digestive
      processes or not.

PMID- 11586777
TI  - The effect of salinity on the emergence and seedling growth of Picea mariana,
      Picea glauca, and Pinus banksiana.
AB  - Mining operations in areas of the boreal forest have caused salinity issues to be
      a major concern for reclamation. One of the factors determining successful
      reclamation is the ability of species to self-propagate. The effects of salinity
      on the seedling emergence and early growth of three boreal forest conifers: Picea
      mariana, Picea glauca, and Pinus banksiana were determined. Seeds were planted in
      sand moistened with solutions of various concentrations of sodium chloride or
      sodium sulfate. Seedling emergence was monitored on a daily basis and growth
      parameters assessed after 6 weeks. The emergence of Pinus banksiana seedlings was
      least affected by salinity, and at certain concentrations, emergence even
      appeared to be stimulated by the presence of salt. Picea glauca was the most
      sensitive of the species studied. Hypertrophia was observed in all species at
      high concentrations of Na2SO4, and an increase in salt levels caused a
      corresponding reduction in seedling height and weight, root length and number of
      lateral roots.

PMID- 11586778
TI  - Evidence of coprostanol estrogenicity to the freshwater mussel Elliptio
      complanata.
AB  - Coprostanol (5 beta (H)-cholestan-3 beta ol) is a reduced metabolite of
      cholesterol produced by micro-organisms found in the intestinal tract of mammals.
      This substance abounds in urban effluents and is accumulated by organisms living
      in the vicinity of municipal effluent outfalls. In an earlier study, freshwater
      mussels exposed to contaminated river water for 62 days accumulated large
      quantities of coprostanol (Cop) in their soft tissues (16 micrograms/g dry wt.).
      Moreover, these mussels were found to have elevated levels of vitellin in their
      hemolymphs, suggesting estrogenic effects. Although municipal wastewaters are
      known to contain other estrogenic compounds capable of inducing Vn synthesis in
      mussels, the estrogenic potential of coprostanol was singled out for examination.
      To this end, mussels were first injected with concentrations of coprostanol via
      the abductor muscle route, and allowed to stand in aerated water for 72 h at 15
      degrees C. The levels of Vn in mussel hemolymph were assayed using the organic
      alkali-labile phosphate method. A competitive estradiol-binding assay was then
      devised to measure the ability of coprostanol to compete in the binding of
      fluorescein-labeled estradiol-albumin to cytosolic proteins. Coprostanol
      partially reversed the binding of labeled estradiol-albumin to cytosolic proteins
      with an EC50 of 1 mM. In addition, injections of coprostanol and estradiol-17
      beta led to increased levels of vitellins in the hemolymph of treated mussels.
      Moreover, incubation of cop in gonad homogenate extracts in the presence of NADPH
      led to the formation of two compounds, as determined by high-performance thin
      layer chromatography. One of these compounds appears to be the C17 oxidation
      product of coprostanol, whose polarity is similar to that of estradiol. The
      results present evidence that coprostanol is estrogenic to freshwater mussels.

PMID- 11586779
TI  - Regulating managers. Rules of engagement.
AB  - Regulation of managers would improve patient safety and managers' credibility.
      Removable offences should include improper conduct. Managers should be required
      to demonstrate competence in people management, finance and information services.
      A regulatory code should incorporate the values of integrity, honesty, openness
      and accountability. In the absence of a regulation system for managers, a medical
      manager struck off by the General Medical Council could go on to manage another
      organisation.

PMID- 11586780
TI  - Nursing recruitment. First impressions.
AB  - Preparations for developing a standard induction programme across 15 trusts for
      overseas nurses in Manchester revealed a wide variation in the terms and
      conditions on which nurses were being employed. Some nurses were not paid at all,
      others were paid as auxiliaries and some were paid as staff nurses. Some
      induction programmes in operation lasted a couple of days, others three or four
      weeks. There should be a minimum two-week induction period. The standard
      programme developed for the area recommends that overseas nurses should be paid a
      minimum of 12,000 Pounds.

PMID- 11586781
TI  - Open space. Stop kidding around.

PMID- 11586782
TI  - Data briefing. Spending under Labour.

PMID- 11586784
TI  - First person. Missing ingredients.

PMID- 11586783
TI  - Hospital inquiries. The listening blank.
AB  - The major failures reported in the Bristol inquiry have been highlighted in most
      hospital inquiry reports over the past 30 years. The tendency to victimise the
      whistleblower has characterised virtually all inquiries. Inadequate leadership,
      isolation, system failures, poor communication and disempowerment of staff and
      service users are the common themes. While organisational reform is essential,
      the real challenge is to change behaviour. And this depends on the example of
      senior staff.

PMID- 11586785
TI  - Hospital food. Today's special.

PMID- 11586786
TI  - Mental health. In good hands.

PMID- 11586787
TI  - Creation of a stable human reporter cell line suitable for FACS-based,
      transdominant genetic selection.
AB  - Quality bioassays are central to all approaches directed at understanding or
      perturbing the function of proteins. One type of cell-based bioassay involves an
      engineered reporter whose transcriptional activity serves as a readout for
      upstream signals of a biochemical pathway(s) that feeds into the reporter. We
      describe a general strategy for creating a mammalian reporter line with
      attributes suitable for a high complexity, en masse transdominant genetic screen.
      The basic criteria required of the mammalian cells engineered with the reporter
      include ease of maintenance, ease of sorting by FACS, ability to be transduced by
      retroviruses, and high expression of transduced peptides or cDNAs. For maximal
      enrichment during selection, the reporter line should have a relatively
      homogeneous response and a high signal-to-background ratio. We use a melanoma
      cell line transduced with a retinoic-acid-responsive promoter coupled to a GFP
      reporter as a case study to demonstrate the strategy. We characterize an
      optimized retinoic-acid-responsive reporter clone to determine the kinetics of
      reporter induction and decay in the presence and absence of retinoids. Dose
      response studies reveal that the reporter responds to all-trans retinoic acid
      with an EC50 of approximately 1 nM. The strategy described is general and may be
      applied to create other reporter lines that respond to a specific stimulus.

PMID- 11586788
TI  - Partial activation of gene activity and chromatin remodeling of the human 14q32.1
      serpin gene cluster by HNF-1 alpha and HNF-4 in fibroblast microcell hybrids.
AB  - The genes encoding alpha 1-antitrypsin (alpha 1AT, gene symbol P I) and
      corticosteroid-binding globulin (CBG) are part of a cluster of serine protease
      inhibitor (serpin) genes on human chromosome 14q32.1. Both genes are highly
      expressed in the liver and in cultured hepatoma cells, and the approximately 100
      kb region around these genes contains an extensive array of expression-associated
      DNase I-hypersensitive sites (DHSs). Activation of human alpha 1AT and CBG
      transcription occurred when human chromosome 14 was transferred from
      nonexpressing cells to rat hepatoma cells. This activation event was accompanied
      by long-range chromatin reorganization of the entire region and the de novo
      formation of 17 expression-associated DHSs. Both gene activation and chromatin
      remodeling in hepatic cells required the liver-enriched transactivators
      hepatocyte nuclear factors-1 alpha and -4 (HNF-1 alpha and HNF-4). In this study,
      we tested whether ectopic expression of HNF-1 alpha and HNF-4 in nonexpressing
      cells could activate alpha 1AT and/or CBG transcription, and we monitored the
      chromatin structure of the locus in stably transfected fibroblasts. We report
      that both alpha 1AT and CBG mRNAs were expressed in fibroblast transfectants that
      stably expressed HNF-1 alpha and HNF-4, but expression was only approximately 1
      10% of that observed in hepatic cells. Gene activation in these cells was
      accompanied by partial chromatin remodeling, as 6 of 17 expression-associated
      DHSs were formed. The potential implications of these results are discussed.

PMID- 11586789
TI  - Deregulated expression of the keratin 18 gene in human colon carcinoma cells.
AB  - The keratin 18 (K18) gene is expressed at a normal level in cells of
      nontumorigenic clones derived from the SW613-S human colon carcinoma cell line,
      but is overexpressed in cells of tumorigenic clones. A high level of expression
      was also found in the cells from 10 of 15 other human colon carcinoma cell lines.
      The expression of the gene is downregulated in differentiating Caco-2 cells,
      resulting in a normal expression level. Determination of K18 mRNA half-life in
      growing and confluent Caco-2 cells indicated that this downregulation does not
      take place at a posttranscriptional level. The density of RNA polymerase
      molecules on the K18 gene, as measured in nuclear run-on experiments, is the same
      in growing and confluent Caco-2 cells, but the rate of synthesis of K18
      transcripts in confluent Caco-2 cells, as determined by in vivo pulse-labeling,
      is 35% of that in growing cells. Nuclear run-on experiments carried out with
      nuclei prepared from growing or confluent Caco-2 cells treated with 5,6-dichloro
      1-beta-D-ribofuranosyl benzimidazole (DRB) indicated that a reduction in both the
      initiation and elongation rates of RNA polymerase molecules occurs on the K18
      gene in confluent Caco-2 cells. This leads to a decreased rate of K18 transcript
      production with no reduction in the polymerase density on the gene. Evidence is
      provided that the mechanisms responsible for the differential expression of the
      K18 gene between tumorigenic and nontumorigenic SW613-S cells and between growing
      and differentiating Caco-2 cells share some similarities.

PMID- 11586790
TI  - Ligand-histone H1 conjugates: increased solubility of DNA complexes, but no
      enhanced transfection activity.
AB  - We introduced galactose and a short RGD sequence as ligands into H1 histone to
      target the asialoglycoprotein receptor or integrins on cells expressing these
      receptors. The efficiency of the gene transfer mediated by galactosylated H1
      histone was strongly affected by the transfection conditions. Galactosylation of
      H1 led to an increase of the basic H1-mediated gene transfer activity only, when
      H1 itself did not develop its optimal transfection activity. Under other
      conditions any specific gene transfer mediated by the asialoglycoprotein receptor
      was covered by the high transfection efficiency of H1 itself. Similar results of
      a marginal increase in the transfection efficiency were obtained by conjugates of
      a short RGD sequence and H1. This unexpected failure in the receptor specificity
      of both conjugates could be due to the unspecific cell-binding capacity of the H1
      moiety and to increasing solubility of the complexes as shown by gel shift and
      solubility measurements.

PMID- 11586791
TI  - Regional mapping panels for human chromosomes 1, 2, and 7.
AB  - The NIGMS Human Genetic Cell Repository has assembled regional mapping panels for
      human chromosomes 1, 2, and 7 from human rodent somatic cell hybrids submitted to
      the collection by researchers from 14 different laboratories. All hybrids were
      characterized initially by the submitters and verified by the Repository. Each
      hybrid carries a stable defined human segment as a derivative or deletion
      chromosome. These panels define 8-10 intervals for each chromosome. The panel for
      chromosome 2 is a new resource. The panels for chromosomes 1 and 7 complement
      previously published panels. The Repository distributes these regional mapping
      panels as cell cultures or as DNA. Information about these panels as well as for
      panels for chromosomes 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 21, 22,
      22, and X may be viewed in the NIGMS Repository electronic catalog
      (http://locus.umdnj.edu/nigms).

PMID- 11586792
TI  - Almost 500,000 to lose M+C.

PMID- 11586793
TI  - Perspectives. Baby boom retirees: demography may be destiny, after all.

PMID- 11586794
TI  - Venturing into new territory.

PMID- 11586795
TI  - Beyond sequencing.

PMID- 11586796
TI  - A contentious decree.

PMID- 11586797
TI  - Stem cell research. Hope ... hype? Hard work.

PMID- 11586798
TI  - Managing your practice. Malpractice claim reviews.

PMID- 11586799
TI  - Pain in perspective.

PMID- 11586800
TI  - Patients' rights and responsibilities.

PMID- 11586801
TI  - Attacking ataxia.

PMID- 11586802
TI  - Pioglitazone and rosiglitazone for diabetes.
AB  - Pioglitazone (Actos-Takeda) and rosiglitazone (Avandia-GlaxoSmithKline) belong to
      a new class of oral antidiabetic medicines (the glitazones or
      thiazolidinediones). Both are licensed in the UK for "oral combination treatment
      of type 2 diabetes mellitus in [narrowly defined groups of] patients with
      insufficient glycaemic control despite maximal tolerated dose of oral monotherapy
      with either metformin or a sulphonylurea". They are not licensed for use as
      monotherapy, in combination with insulin, or as part of triple therapy with
      metformin or a sulphonylurea. What can pioglitazone and rosiglitazone offer in
      the management of patients with type 2 diabetes?

PMID- 11586803
TI  - Bisphosphonates for osteoporosis.
AB  - One in three women and at least one in 12 men in the UK have osteoporosis, a
      condition which can lead to fractures, deformity, pain and disability, at a cost
      to the NHS of around 1.5 billion Pounds each year. Bisphosphonates offer a
      therapeutic option for preventing and treating osteoporosis. Here, we assess and
      compare the three bisphosphonates (alendronate, etidronate and risedronate)
      licensed for such use in the UK. We do not consider the four bisphosphonates
      (clodronate, pamidronate, tiludronate and zoledronate) that are licensed in the
      UK only for the treatment of Paget's disease of bone and/or hypercalcaemia of
      malignancy.

PMID- 11586804
TI  - [For safer health care: Analyse the "human factor"!].

PMID- 11586806
TI  - [Essential to monitor vaccine safety].
AB  - Vaccinations are one of the most successful public health measures. However,
      vaccinations are not without risks. An improved infrastructure is needed to
      facilitate the conduct of large clinical trials and/or phase IV studies.
      Vaccination registers and large linked database studies are examples of such
      structural improvements. A vaccination register pilot project carried out by the
      Swedish Institute of Infectious Disease Control (SIIDC) showed that parents with
      few exceptions gave consent to enrolling their children in the pilot register and
      that bar code labelling of vaccines is a reliable and practical manner in which
      to record vaccinations. Two EU projects with the aim to improve the information
      infrastructure have recently started. In the project Development of Vaccination
      Registers existing and planned immunisation registers are reviewed and a plan of
      action will be proposed. The aim of the project EUSAFEVAC is to improve vaccine
      safety through systematic reviews of the literature, to develop standard case
      definitions, to develop a model immunisation register and to improve reporting
      systems. SIIDC in collaboration with the Swedish National Board for Health and
      Welfare and the Medical Products Agency is exploring the feasibility of
      establishing a Swedish immunisation register and linked database information
      system.

PMID- 11586805
TI  - [Simulator training in medicine and health care. A new pedagogic model for good
      patient safety].
AB  - Advanced simulation within medicine and health care is a rapidly growing field.
      Simulator based training can be applied in minimal invasive surgery, in
      endoscopic procedures as well as in anaesthesia and critical care management. At
      Huddinge University Hospital a center for advanced simulation of both endoscopic
      surgery and anaesthesia/critical care management is currently being set up. The
      objective is to focus on improved medical and health care training and thus
      improving patient safety by reducing medical errors.

PMID- 11586807
TI  - [Give all children vaccine against hepatitis B!].
AB  - The number of individuals with chronic hepatitis B in Sweden has increased,
      mainly due to new immigrant groups. A safe and effective hepatitis B vaccine
      exists which allows a flexible dosing schedule. Most countries in the world
      adheres to the WHO recommendations to include this vaccine in the childhood
      vaccination regimen. This has led to a substantial drop in morbidity and
      mortality from hepatitis B virus infections in high endemic regions such as
      Taiwan. Sweden should consider changing its vaccination policy, including the
      vaccination of high risk groups only, and consider vaccination of all infants.

PMID- 11586808
TI  - [A new British study: No connection between vaccination and sudden infant death].

PMID- 11586809
TI  - [Blood lipid derangement common in peripheral artery disease. Lipid-lowering
      agents may alleviate symptoms and slow the atherosclerotic process].
AB  - In the new guidelines from the Swedish Medical Products Agency, an aggressive
      approach is recommended for the treatment of hyperlipidemia in all patients with
      manifest atherosclerotic disease. Patients with intermittent claudication should
      therefore receive lipid-lowering treatment on the same indications as patients
      with coronary artery disease. The present article reviews our knowledge of
      hyperlipidemia as a risk factor for the development of peripheral artery disease.
      Hyperlipidemia is frequently found in these patients and the most common lipid
      derangements are low levels of HDL-cholesterol and hypertriglyceridemia. Hard end
      point data concerning morbidity and mortality during lipid-lowering treatment in
      this specific population is largely lacking, although previous studies indicate
      that lipid-lowering treatment slows the atherosclerotic process and induces pain
      relief.

PMID- 11586810
TI  - [Reduced prevalence of dementia in patients treated with antilipemic agents. An
      overview of cholesterol metabolism in the brain and actions].

PMID- 11586811
TI  - [Significance of prenatal exposure for long-term health effects].
AB  - A rapidly accumulating body of evidence indicates that many diseases must be
      understood in a life-long perspective, as trajectories that start at conception
      and surface upon clinical detection decades later. We know that some toxic
      intrauterine exposures may have life-long consequences, such as alcohol and some
      environmental pollutants, but it was not expected that chronic diseases such as
      cardiovascular disease or some cancers may have a fetal origin. Several research
      findings indicate that this expectation should be revised. Some studies indicate
      that sperm counts are declining conceiving the desired number of children. The so
      called "estrogen hypothesis" states that this may be due to exposures in the
      intrauterine environment. About 10 years ago it was suggested that breast cancer
      originates in utero, which may be true also for cancer of the prostate or ovary.
      So far the evidence for this hypothesis is only circumstantial, but results have
      supported the idea. A large number of studies clearly indicate that impaired
      fetal growth is associated with a number of diseases. It is well known that all
      organs have time periods of rapid growth which may render them vulnerable to an
      insufficient supply of nutrition; impaired growth could alter organ structure and
      functioning, and the fetus could e.g. develop insulin resistance to protect
      itself from these "hunger" periods. "Organ programming" may be a fact we should
      consider when studying the etiology of e.g. cardiovascular diseases. These
      hypotheses--if they should hold true--are promising for new approaches to
      prevention. Much more work is needed however, before we can visualize these
      avenues of prevention, and we should make sure we develop the opportunities for
      doing this work now. It is high time.

PMID- 11586812
TI  - [A case report. Non-traumatic leg pain with rare pathogenesis].

PMID- 11586813
TI  - [Prothromplex in stead of Beriplex P/N as acute antidote against warfarin].

PMID- 11586814
TI  - [The new gene technology--another challenge for primary health care].

PMID- 11586815
TI  - [In the air force mistakes are converted into knowledge. When will the health
      care deal with safety issues seriously?].

PMID- 11586816
TI  - [The amalgam syndrome seen in the perspective of history of ideas. Mercury-
      useful product and health hazard].

PMID- 11586817
TI  - [Forensic psychiatric tests and legal rights--a reply].

PMID- 11586818
TI  - [Will male circumcision be forbidden in four years?].

PMID- 11586819
TI  - [Low level of the debate on alternative medicine].

PMID- 11586820
TI  - [Wrong conclusions of a questionnaire about medical students and euthanasia].

PMID- 11586821
TI  - [A physician can support capital punishment].

PMID- 11586822
TI  - [Current paracetamol package is practical to many].

PMID- 11586823
TI  - [What is the outcome of PCR for M tuberculosis in biopsy?].

PMID- 11586824
TI  - [Symptoms, not diagnoses, are the basis of priority].

PMID- 11586825
TI  - [How to inform of severe disease?].

PMID- 11586826
TI  - [Preserve us from reintroduction of the Hippocratic Oath!].

PMID- 11586827
TI  - [The evidence-based medicine is necessary but not sufficient. Areas with
      insufficient scientific basis should be completed].

PMID- 11586828
TI  - [A welcomed SBU report shows efficient methods against abuse. But certain parts
      are already out of date].

PMID- 11586829
TI  - [The SBU report on hazardous alcohol consumption, alcohol abuse and narcotic
      dependence. Simple, but efficient measures in health care are not provided
      frequently enough].

PMID- 11586830
TI  - [Research results should be freely accessible!-- Case reports demonstrate
      obstacles to contact with drug industry].
AB  - Recommendations on the use of medical technologies should be based on best
      available evidence. Publication bias due to delayed publication or non
      publication of negative studies leads to inflated effect sizes in systematic
      reviews. We carried out a health technology assessment on prevention and
      treatment of venous thromboembolism, and in order to minimize publication bias
      asked the six pharmaceutical companies with antithrombotic drugs registered in
      Sweden to supply us with results from unpublished clinical trials. The answers
      were returned after 4 to 60 weeks, and with only one exception, after multiple
      reminders by telephone, fax and e-mail. No relevant unpublished studies were
      reported to us although we were made aware of two published studies that our
      literature search had not identified. One company did not mention a large
      negative unpublished clinical trial with their drug which has remained
      unpublished due to conflict between the company and the steering committee. We
      conclude that the companies did not contribute much and that the process was very
      time consuming with little result. As non-publication of trial results is
      unethical, we propose agreements between industry and researchers that all
      studies be prospectively registered and made publicly available.

PMID- 11586831
TI  - [New in vitro analysis tested: bleeding time is still the best method for
      evaluation of primary hemostasis].
AB  - The need is great for a simple, cheap and readily accessible method for the
      evaluation of primary hemostasis in work-ups at both out-patient clinics and
      units caring for surgical or intensive care patients. PFA-100 is a recently
      introduced instrument for in vitro testing of platelet function. We report
      experiences from Stockholm, Gothenburg and Malmo of PFA-100 measurements
      performed on samples from healthy controls and from patients with von Willebrand
      disease or platelet disorders. It is shown that the PFA-100 system has a high
      sensitivity for von Willebrands disease, while the sensitivity for hereditary
      platelet dysfunction is low. In its present design this new device could not
      replace the template bleeding time as a screening test for primary hemostasis.

PMID- 11586832
TI  - [Collective ethical rules nothing for Swedish physicians. The Swedish Medical
      Society reluctantly accepted a codex ethicus first in 1951].

PMID- 11586833
TI  - [Why are Swedish physicians not taking the oath?].

PMID- 11586834
TI  - [The first physicians' rules are interesting documents of the time].

PMID- 11586835
TI  - [The amalgam syndrome from a historical perspective. The Swedish amalgam disease
      epidemics].

PMID- 11586836
TI  - [The sausage duel which never took place].

PMID- 11586837
TI  - [Use of a new drug in the treatment of heroin addicts should not be obstructed by
      political dogmatism].

PMID- 11586838
TI  - [Legal rights are not jeopardized by the Rorschach test].

PMID- 11586839
TI  - [Corrected conclusion in the SBU report: no supplementary effect of theophylline
      in acute, moderate asthma, but this is not documented in severe life-threatening
      asthma].

PMID- 11586840
TI  - [How much should the diagnosis of pulmonary embolism cost?].

PMID- 11586841
TI  - [The war between tabloids nothing new].

PMID- 11586842
TI  - [Test basis of conclusions about NEPI].

PMID- 11586843
TI  - I. The body, the brain, hormones. The biology of aging.

PMID- 11586844
TI  - I. The body, the brain, hormones. The brain in winter.

PMID- 11586845
TI  - I. The body, the brain, hormones. Taming raging hormones.

PMID- 11586846
TI  - I. The body, the brain, hormones. The myth of old age.

PMID- 11586847
TI  - II. Fitness, nutrition, beauty. Fighting back, with sweat.

PMID- 11586848
TI  - Living longer. Health for life.

PMID- 11586849
TI  - II. Fitness, nutrition, beauty. More veggies, please.

PMID- 11586850
TI  - II. Fitness, nutrition, beauty. Turning back the clock.

PMID- 11586852
TI  - III. Mind, moods and stress. Thanks for the memories.

PMID- 11586851
TI  - II. Fitness, nutrition, beauty. What the nurses know.

PMID- 11586853
TI  - III. Mind, moods and stress. Keeping hope alive.

PMID- 11586854
TI  - III. Mind, moods and stress. The many faces I see.

PMID- 11586855
TI  - IV. Genes, cells, drugs. Cures for the future. Can we overcome cancer?

PMID- 11586856
TI  - IV. Genes, cells, drugs. Cures for the future. Skin and bones to order.

PMID- 11586857
TI  - IV. Genes, cells, drugs. Cures for the future. The heart of the matter.

PMID- 11586858
TI  - IV. Genes, cells, drugs. Cures for the future. New DNA in old bodies.

PMID- 11586860
TI  - Your body what happens ... what helps.

PMID- 11586859
TI  - IV. Genes, cells, drugs. Cures for the future. Fountains of youth.

PMID- 11586862
TI  - Carolyn Farb: first lady of philanthropy.
AB  - From cancer and medical research, children's and women's issues, to arts,
      education, and culture, Carolyn Farb's skill as a volunteer fund raiser has been
      fine-tuned to equal that of the best professional fund raisers in the country.
      She has made chairing successful charitable events an art form and unselfish
      life's occupation.

PMID- 11586861
TI  - Bites and stings due to terrestrial and aquatic animals in Europe.

PMID- 11586863
TI  - Gift planning in the year 2010: imagine the unimaginable. Part I.
AB  - Philanthropy in general, and fund raising in particular, is changing. Such change
      is more radical than most recognize and certainly faster than most organizations
      are prepared for. Those that anticipate the change and adjust to it have a good
      chance of thriving. Those that fail to do so will struggle and may become
      irrelevant.

PMID- 11586864
TI  - Letter-opening copy: what TV journalists can teach us about teasing donors, and
      getting them to open our mail.

PMID- 11586865
TI  - Content strategy.

PMID- 11586867
TI  - Try a fund-raising triage.
AB  - Not-for-profit organizations which strengthen society and the individuals who
      make up that society both face times of crisis in their lives. The struggle of
      charitable endeavors may lack the breath and blood drama of the catastrophe
      scene, but their need for professional gift support priority decisions may prove
      to be equally crucial for their future existence.

PMID- 11586866
TI  - Where are the leaders?
AB  - The CEO, CAO and Board Chair constitute a non-profit's "power team." How
      effectively these leaders can combine their individual skills--specifically in
      mutually supportive ways--determines the critical difference between a non
      profit's success or failure.

PMID- 11586868
TI  - Overview and summary of findings: School Health Policies and Programs Study 2000.

PMID- 11586869
TI  - Methodology for the School Health Policies and Programs Study 2000.

PMID- 11586870
TI  - Health education: results from the School Health Policies and Programs Study
      2000.

PMID- 11586871
TI  - Physical education and activity: results from the School Health Policies and
      Programs Study 2000.

PMID- 11586872
TI  - Health services: results from the School Health Policies and Programs Study 2000.

PMID- 11586873
TI  - Mental health and social services: results from the School Health Policies and
      Programs Study 2000.

PMID- 11586874
TI  - Food service and foods and beverages available at school: results from the School
      Health Policies and Programs Study 2000.

PMID- 11586875
TI  - School policy and environment: results from the School Health Policies and
      Programs Study 2000.

PMID- 11586876
TI  - Faculty and staff health promotion: results from the School Health Policies and
      Programs Study 2000.

PMID- 11586877
TI  - Family and community involvement in schools: results from the School Health
      Policies and Programs Study 2000.

PMID- 11586878
TI  - Europe's patent rebellion.

PMID- 11586879
TI  - Henry Genet Taylor, MD. The Civil War and its aftermath.

PMID- 11586880
TI  - MSNJ's judicial review process.

PMID- 11586881
TI  - Legal update: collateral source rule.

PMID- 11586882
TI  - Professional liability insurance: IV. Evaluating professional liability carriers.

PMID- 11586883
TI  - Updated recommendations for reducing vertical HIV transmission.

PMID- 11586884
TI  - Patients' bill of rights.

PMID- 11586885
TI  - Monitoring activation of ribonuclease L by 2',5'-oligoadenylates using purified
      recombinant enzyme and intact malignant glioma cells.
AB  - A wide range of methods have been developed to study RNase L activation in cell
      free systems and in intact cells. Many of the original methods were developed in
      the laboratory of I. Kerr in the early 1980s (e.g., see Knight et al.).
      Additional methods described in this article were developed or adapted from
      research in other fields after the cloning of RNase L and the appreciation of its
      role in apoptosis. These methods provide the basic techniques needed to induce
      RNase L activation in vitro and to measure some of its biological effects in
      living mammalian cells.

PMID- 11586886
TI  - Saccharomyces cerevisiae nuclear ribonuclease P: structure and function.

PMID- 11586887
TI  - Cyanelle ribonuclease P: isolation and structure-function studies of an
      organellar ribonucleoprotein enzyme.

PMID- 11586888
TI  - Characterization of ribonuclease MRP function.

PMID- 11586889
TI  - Escherichia coli ribonuclease III: affinity purification of hexahistidine-tagged
      enzyme and assays for substrate binding and cleavage.
AB  - It is now evident that members of the RNase III family of nucleases have central
      roles in prokaryotic and eukaryotic RNA maturation and decay pathways. Ongoing
      research is uncovering new roles for RNase III homologs. For example, the
      phenomena of RNA interference (RNAi) and posttranscriptional gene silencing
      (PTGS) involve dsRNA processing, carried out by an RNase III homolog. We
      anticipate an increased focus on the mechanism, regulation, and biological roles
      of RNase III orthologs. Although the differences in the physicochemical
      properties of RNase III orthologs, and distinct substrate reactivity epitopes and
      ionic requirements for optimal activity, may mean that the protocols describe
      here are not strictly transferrable, the affinity purification methodology, and
      substrate preparation and use should be generally applicable.

PMID- 11586890
TI  - Purification and characterization of Saccharomyces cerevisiae Rnt1p nuclease.
AB  - In this article, we have described methods used to purify Rnt1p and study its
      biochemical properties. Rnt1p can be easily purified from bacteria as N-terminal
      His6-tagged protein and its activity may be monitored in vitro. Rnt1p cleaves the
      RNA by binding to a cleavage site followed by hydrolysis and product release. The
      kinetic parameters of Rnt1p are similar to those of other nucleases, including
      bacterial RNase III. The ability of Rnt1p to bind substrate without cleaving it
      in the absence of divalent metal ions provides a convenient means to study RNA
      recognition and binding independent of catalysis. The gel mobility shift and in
      the-gel cleavage assays described here reveal the formation of two Rnt1p-RNA
      complexes with different cleavage activities, suggesting that the protein may
      bind the substrate in two different forms or through a two-step binding reaction.

PMID- 11586891
TI  - Pac1 ribonuclease of Schizosaccharomyces pombe.

PMID- 11586892
TI  - Dictyostelium double-stranded ribonuclease.

PMID- 11586893
TI  - Accelerating RNA decay through intervention of RNase L: alternative synthesis of
      composite 2',5'-oligoadenylate-antisense.

PMID- 11586894
TI  - Double-stranded RNA nuclease associated with rye germ ribosomes.

PMID- 11586895
TI  - Yeast mRNA decapping enzyme.

PMID- 11586896
TI  - RNA lariat debranching enzyme.

PMID- 11586897
TI  - 5'-exoribonuclease 1: Xrn1.

PMID- 11586898
TI  - Rat1p nuclease.

PMID- 11586899
TI  - Analysis of XRN orthologs by complementation of yeast mutants and localization of
      XRN-GFP fusion proteins.

PMID- 11586900
TI  - Polysomal ribonuclease 1.

PMID- 11586901
TI  - 5'-->3'-exoribonuclease from rabbit reticulocytes.

PMID- 11586902
TI  - Drosophila 5'-->3'-exoribonuclease Pacman.

PMID- 11586903
TI  - Purification and activity assays of the catalytic domains of the
      kinase/endoribonuclease Ire1p from Saccharomyces cerevisiae.

PMID- 11586904
TI  - Purification of poly(A)-specific ribonuclease.

PMID- 11586905
TI  - Escherichia coli ribonuclease II.

PMID- 11586906
TI  - Escherichia coli RNA degradosome.

PMID- 11586907
TI  - Preparation of Escherichia coli Rne protein and reconstitution of RNA
      degradosome.

PMID- 11586908
TI  - Purification of yeast exosome.

PMID- 11586909
TI  - Genetic and biochemical approaches for analysis of mitochondrial degradosome from
      Saccharomyces cerevisiae.

PMID- 11586911
TI  - Chlamydomonas reinhardtii as a model system for dissecting chloroplast RNA
      processing and decay mechanisms.

PMID- 11586912
TI  - Chloroplast mRNA 3'-end nuclease complex.

PMID- 11586910
TI  - Direct sizing of RNA fragments using RNase-generated standards.

PMID- 11586914
TI  - Erns protein of pestiviruses.

PMID- 11586913
TI  - Chloroplast p54 endoribonuclease.

PMID- 11586916
TI  - Herpes simplex virus vhs protein.

PMID- 11586915
TI  - Liver perchloric acid-soluble ribonuclease.

PMID- 11586917
TI  - Influenza virus endoribonuclease.
AB  - The influenza virus polymerase complex contains two associated enzymatic
      activities, an endoribonuclease and a RNA-dependent RNA polymerase activity. Both
      activities have so far been observed only with the complete polymerase complex
      consisting of three subunits, PB1, PB2, and PA. This chapter describes a robust
      and optimized procedure for the purification of active influenza virus polymerase
      in complex with genomic RNA and the single-stranded RNA-binding protein
      nucleoprotein from influenza virus particles. It also explains the synthesis of
      capped RNA molecules as substrates of the influenza virus endonuclease. The
      enzymatic properties of influenza virus-derived endoribonuclease activity have
      been characterized with a model RNA substrate of 20-nucleotide length, termed G20
      RNA. The rate of RNA cleavage under steady state conditions appears to be limited
      by product dissociation. Therefore conditions have been optimized to study the
      chemical step of RNA cleavage under single turnover conditions. The enzyme
      requires divalent metal ions for activity and can use Mn(II), Co(II), and Fe(II)
      efficiently at pH 7, Mg(II) with intermediate efficiency, and Ni(II) and Zn(II)
      with lower efficiency. The reaction progress curves show slow binding of Zn(II)
      and Ni(II) to the protein, suggesting a conformational change of the active site
      as a prerequisite for endonuclease activity in the presence of these two metal
      ions. Low concentrations of the detergent DOC inhibit the activity and also
      disrupt the trimeric polymerase complex, whereas other detergents do not have a
      significant effect on the activity.

PMID- 11586918
TI  - Bacteriophage T4 RegB endoribonuclease.

PMID- 11586919
TI  - Escherichia coli ribonuclease G.

PMID- 11586920
TI  - Escherichia coli transcript cleavage factors GreA and GreB: functions and
      mechanisms of action.

PMID- 11586921
TI  - Escherichia coli ribonuclease P.

PMID- 11586922
TI  - Human ribonuclease P.

PMID- 11586923
TI  - On writing for publication.
AB  - Every action people take has a ripple effect on others. Whether they work at the
      bench, as a manager, as an educator, or in some other position, laboratorians
      make a difference in the lives of patients, colleagues, students, and the general
      public. We need to talk with others about professional issues, inside and outside
      our profession. One way to connect with others is through writing articles. This
      article streamlines writing processes for laboratorians (regardless of whether
      they are experienced writers, writing novices, or have never written anything for
      publication before) by presenting useful checklists and suggestions that can ease
      the way to writing for publication.

PMID- 11586924
TI  - What we have learned from other departments or functional areas.

PMID- 11586925
TI  - Case studies in ethics. The integrity of academic research.

PMID- 11586926
TI  - Dollar$ & $en$e. Common cent$ 2: Booms, busts, bears, and bulls.

PMID- 11586927
TI  - Staffing savvy. The same side of the fence, Part 2. Managers, educators, and
      health-care administrators all depend on each other.

PMID- 11586928
TI  - Clinical systems management matters. Expanded responsibilities.

PMID- 11586930
TI  - After the trauma.

PMID- 11586929
TI  - As we see it. The medical technology profession: a paradigm shift.

PMID- 11586931
TI  - Hitting home.

PMID- 11586932
TI  - Role of viral load blips, drug boosting, and therapeutic holidays in HIV patient
      management.

PMID- 11586934
TI  - Fatty acid ethyl esters: markers of ethanol intake.

PMID- 11586933
TI  - The hepatitis C infection process.

PMID- 11586935
TI  - LabAutomation 2001. Part 4: Mass spectroscopy as sensitive detector, protein
      function in disease, and the soul of a robot.

PMID- 11586936
TI  - A sequence-based method for the accurate identification of drug-resistant HIV-1
      mutations.

PMID- 11586937
TI  - Laboratory testing vs at-home glucose readings in monitoring diabetes.

PMID- 11586938
TI  - Detection of low levels of Listeria monocytogenes within 20 hours using an
      evanescent wave biosensor.

PMID- 11586939
TI  - Psoriasis: new drugs on the horizon?

PMID- 11586940
TI  - Redefining myocardial infarction: meeting the challenge with a sensitive and
      specific troponin assay.

PMID- 11586941
TI  - Role of the laboratory in leveraging adoption of pharmacogenetics.

PMID- 11586942
TI  - Determination of nonmetabolized organohalogen solvents in human urine by thin
      layer headspace analysis.

PMID- 11586943
TI  - Product introductions at 2001 CLMA and AACC: Part 1.

PMID- 11586944
TI  - After the attack. Answering questions.

PMID- 11586945
TI  - After the attack: horror and heroes. Ground zero.

PMID- 11586946
TI  - Proceedings of the 2nd Workshop on the Biology of Ultraviolet and Polarization
      Vision. Victoria, British Columbia, Canada. 20-25 June 2000.

PMID- 11586947
TI  - Structure and Assembly of Retroviruses. 14-18 October 2000. Abstracts.

PMID- 11586950
TI  - Bibliography. Current world literature. Interstitial lung disease.

PMID- 11586949
TI  - The Speaking of Food and Eating Award. Excellence in consumer nutrition
      communication.

PMID- 11586951
TI  - Bibliography. Current world literature. Disorders of pulmonary circulation.

PMID- 11586952
TI  - Widespread distribution of urinary tract infections caused by a multidrug
      resistant Escherichia coli clonal group.
AB  - BACKGROUND: The management of urinary tract infections is complicated by the
      increasing prevalence of antibiotic-resistant strains of Escherichia coli. We
      studied the clonal composition of E. coli isolates that were resistant to
      trimethoprim-sulfamethoxazole from women with community-acquired urinary tract
      infections. METHODS: Prospectively collected E. coli isolates from women with
      urinary tract infections in a university community in California were evaluated
      for antibiotic susceptibility, O:H serotype, DNA fingerprinting, pulsed-field gel
      electrophoretic pattern, and virulence factors. The prevalence and
      characteristics of an antibiotic-resistant clone were evaluated in this group of
      isolates and in those from comparison cohorts in Michigan and Minnesota. RESULTS:
      Fifty-five of the 255 E. coli isolates (22 percent) from the California cohort
      were resistant to trimethoprim-sulfamethoxazole as well as other antibiotics.
      There was a common pattern of DNA fingerprinting, suggesting that the isolates
      belonged to the same clonal group (clonal group A), in 28 of 55 isolates with
      trimethoprim-sulfamethoxazole resistance (51 percent) and in 2 of 50 randomly
      selected isolates that were susceptible to trimethoprim-sulfamethoxazole (4
      percent, P<0.001). In addition, 11 of 29 resistant isolates (38 percent) from the
      Michigan cohort and 7 of 18 (39 percent) from the Minnesota cohort belonged to
      clonal group A. Most of the clonal group A isolates were serotype O11:H(nt) or
      O77:H(nt), with similar patterns of virulence factors, antibiotic susceptibility,
      and electrophoretic features. CONCLUSIONS: In three geographically diverse
      communities, a single clonal group accounted for nearly half of community
      acquired urinary tract infections in women that were caused by E. coli strains
      with resistance to trimethoprim-sulfamethoxazole. The widespread distribution and
      high prevalence of E. coli clonal group A has major public health implications.

PMID- 11586953
TI  - The prognostic value of B-type natriuretic peptide in patients with acute
      coronary syndromes.
AB  - BACKGROUND: Brain (B-type) natriuretic peptide is a neurohormone synthesized
      predominantly in ventricular myocardium. Although the circulating level of this
      neurohormone has been shown to provide independent prognostic information in
      patients with transmural myocardial infarction, few data are available for
      patients with acute coronary syndromes in the absence of ST-segment elevation.
      METHODS: We measured B-type natriuretic peptide in plasma specimens obtained a
      mean (+/-SD) of 40+/-20 hours after the onset of ischemic symptoms in 2525
      patients from the Orbofiban in Patients with Unstable Coronary Syndromes
      Thrombolysis in Myocardial Infarction 16 study. RESULTS: The base-line level of B
      type natriuretic peptide was correlated with the risk of death, heart failure,
      and myocardial infarction at 30 days and 10 months. The unadjusted rate of death
      increased in a stepwise fashion among patients in increasing quartiles of base
      line B-type natriuretic peptide levels (P< 0.001). This association remained
      significant in subgroups of patients who had myocardial infarction with ST
      segment elevation (P=0.02), patients who had myocardial infarction without ST
      segment elevation (P<0.001), and patients who had unstable angina (P<0.001).
      After adjustment for independent predictors of the long-term risk of death, the
      odds ratios for death at 10 months in the second, third, and fourth quartiles of
      B-type natriuretic peptide were 3.8 (95 percent confidence interval, 1.1 to
      13.3), 4.0 (95 percent confidence interval, 1.2 to 13.7), and 5.8 (95 percent
      confidence interval, 1.7 to 19.7). The level of B-type natriuretic peptide was
      also associated with the risk of new or recurrent myocardial infarction (P=0.01)
      and new or worsening heart failure (P<0.001) at 10 months. CONCLUSIONS: A single
      measurement of B-type natriuretic peptide, obtained in the first few days after
      the onset of ischemic symptoms, provides powerful information for use in risk
      stratification across the spectrum of acute coronary syndromes. This finding
      suggests that cardiac neurohormonal activation may be a unifying feature among
      patients at high risk for death after acute coronary syndromes.

PMID- 11586954
TI  - Pregnancy-associated plasma protein A as a marker of acute coronary syndromes.
AB  - BACKGROUND: Circulating markers indicating the instability of atherosclerotic
      plaques could have diagnostic value in unstable angina or acute myocardial
      infarction. We evaluated pregnancy-associated plasma protein A (PAPP-A), a
      potentially proatherosclerotic metalloproteinase, as a marker of acute coronary
      syndromes. METHODS: We examined the level of expression of PAPP-A in eight
      culprit unstable coronary plaques and four stable plaques from eight patients who
      had died suddenly of cardiac causes. We also measured circulating levels of PAPP
      A, C-reactive protein, and insulin-like growth factor I (IGF-I) in 17 patients
      with acute myocardial infarction, 20 with unstable angina, 19 with stable angina,
      and 13 controls without atherosclerosis. RESULTS: PAPP-A was abundantly expressed
      in plaque cells and extracellular matrix of ruptured and eroded unstable plaques,
      but not in stable plaques. Circulating PAPP-A levels were significantly higher in
      patients with unstable angina or acute myocardial infarction than in patients
      with stable angina and controls (P<0.001). A PAPP-A threshold value of 10 mlU per
      liter identified patients who had acute coronary syndromes with a sensitivity of
      89.2 percent and a specificity of 81.3 percent. PAPP-A levels correlated with
      levels of C-reactive protein and free IGF-I, but not with markers of myocardial
      injury (troponin I and the MB isoform of creatine kinase). CONCLUSIONS: PAPP-A is
      present in unstable plaques, and circulating levels are elevated in acute
      coronary syndromes; these increased levels may reflect the instability of
      atherosclerotic plaques. PAPP-A is a new candidate marker of unstable angina and
      acute myocardial infarction.

PMID- 11586955
TI  - The effect of common polymorphisms of the beta2-adrenergic receptor on agonist
      mediated vascular desensitization.
AB  - BACKGROUND: With continuous exposure to beta2-adrenergic agonists, vascular
      tissue becomes desensitized to agonist-mediated vasodilatation. We studied the
      effects of two common polymorphisms of the beta2-adrenergic receptor, one at
      codon 16 and one at codon 27, on agonist-mediated vasodilatation and
      desensitization in the vascular bed. METHODS: We studied 26 healthy subjects who
      were selected to represent three genotypes: 7 were homozygous for the alleles
      encoding Arg16 and Gln27, 8 were homozygous for the alleles encoding Gly16 and
      Gln27, and 11 were homozygous for the alleles encoding Gly16 and Glu27. Vascular
      responses were assessed by measuring changes in the diameter of a dorsal hand
      vein. A dose-response curve of the effect of the beta2-adrenergic-receptor
      agonist isoproterenol was constructed (dose range, 4 to 480 ng per minute).
      Desensitization was then induced by a 2-hour continuous infusion of
      isoproterenol, and venodilatation was measured 30, 60, 90, and 120 minutes after
      the start of the infusion. RESULTS: Subjects who were homozygous for Arg16 had
      almost complete desensitization; venodilatation in response to isoproterenol in
      this group decreased from a mean (+/-SE) of 44+/-11 percent to 8+/-4 percent
      (P=0.006). In contrast, subjects who were homozygous for Gly16 did not have
      significant desensitization, irrespective of the amino acid encoded by codon 27.
      Subjects who were homozygous for Glu27 had higher maximal venodilatation in
      response to isoproterenol than those who were homozygous for Gln27 (86+/-13
      percent vs. 54+/-8 percent, P=0.03). CONCLUSIONS: The Arg16 polymorphism of the
      beta2-adrenergic receptor is associated with enhanced agonist-mediated
      desensitization in the vasculature, and the Glu27 polymorphism is associated with
      increased agonist-mediated responsiveness. Therefore, polymorphisms of the beta2
      adrenergic receptor are potentially important determinants of the vascular
      response to stress.

PMID- 11586956
TI  - Development of type 1 diabetes despite severe hereditary B-cell deficiency.

PMID- 11586957
TI  - Images in clinical medicine. Mucinous cystadenoma.

PMID- 11586958
TI  - Vaccines and vaccination.

PMID- 11586959
TI  - An epidemic of urinary tract infections?

PMID- 11586960
TI  - Acute coronary syndromes--beyond myocyte necrosis.

PMID- 11586961
TI  - Closing in on type 1 diabetes.

PMID- 11586962
TI  - A gene responsible for familial Wolff-Parkinson-White syndrome.

PMID- 11586963
TI  - Deaths and injuries from house fires.

PMID- 11586964
TI  - Deaths and injuries from house fires.

PMID- 11586965
TI  - Deaths and injuries from house fires.

PMID- 11586966
TI  - Clinical response to fluorouracil and p53.

PMID- 11586967
TI  - Hemophilia.

PMID- 11586968
TI  - Hemophilia.

PMID- 11586969
TI  - Hemophilia.

PMID- 11586970
TI  - Selection of spermatozoa with normal nuclei to improve the pregnancy rate with
      intracytoplasmic sperm injection.

PMID- 11586971
TI  - Asthma caused by a cathedral wall.

PMID- 11586972
TI  - Images in clinical medicine. Porphyria cutanea tarda.

PMID- 11586973
TI  - Cerebrovascular surgery: past, present, and future.

PMID- 11586974
TI  - Natural history of brainstem cavernous malformations.

PMID- 11586975
TI  - Abstracts of the XXVIII European Society for Artificial Organs Congress. Gent,
      Belgium, 22-25 September 2001.

PMID- 11586976
TI  - 33rd Annual Oak Ridge Conference. The post genome era: new targets and new
      technologies. May 4-5, 2001. Seattle, Washington, USA. Proceedings and abstracts.

PMID- 11586977
TI  - 24th European Conference on Visual Perception. Kusadasi, Turkey. 26-30 August
      2001. Abstracts.

PMID- 11586978
TI  - Safety profile of bupropion for chronic obstructive pulmonary disease.

PMID- 11586979
TI  - Safety profile of bupropion for chronic obstructive pulmonary disease.

PMID- 11586980
TI  - Safety profile of bupropion for chronic obstructive pulmonary disease.

PMID- 11586981
TI  - Extrapulmonary tuberculosis.

PMID- 11586982
TI  - Smoking cessation and major depression.

PMID- 11586983
TI  - Smoking cessation and major depression.

PMID- 11586984
TI  - Chronic renal disease.

PMID- 11586985
TI  - Chronic renal disease.

PMID- 11586986
TI  - Guardianship in research.

PMID- 11586987
TI  - The Canadian CT Head Rule.

PMID- 11586988
TI  - The Canadian CT Head Rule.

PMID- 11586989
TI  - Phantom limb pain.

PMID- 11586990
TI  - Pitfalls of new long-term care insurance in Japan.

PMID- 11586991
TI  - Absence of viral transmission in injecting drug users in Russia.

PMID- 11586992
TI  - Betamethasone in threatened preterm labour.

PMID- 11586993
TI  - Is Gandhi's philosophy of non-violence dead in Nepal?

PMID- 11586995
TI  - [Will everything go well? For human-paced progress].

PMID- 11586996
TI  - [Changes in ultra rapid urease test and histopathological examination for
      Helicobacter pylori by antisecretory drugs].
AB  - BACKGROUND: One of the major problems when evaluating dyspeptic patients at
      public hospitals is the large interval between the consultation and the
      endoscopy, leading to the prescription of antisecretory drugs, what can be
      responsible for false results on examinations. AIM: To evaluate changes in
      ultrarapid urease test and histopathological examination for Helicobacter pylori
      by antisecretory drugs. METHODS: In a prospective double-blind study, 50 patients
      with dyspeptic complaints and endoscopic diagnosis of peptic ulcer, erosive
      gastritis, esophagitis or duodenitis with a positive urease test, were randomized
      to a 7-day course of treatment with either omeprazole 20 mg or ranitidine 300 mg
      a day. Before and after treatment, two biopsy specimens each were obtained from
      the antrum and corpus and an ultrarapid urease test and a histopathological
      examination for Helicobacter pylori were performed. RESULTS: There were no
      significant changes in the results of ultrarapid urease test and
      histopathological examination for Helicobacter pylori after treatment with
      ranitidine. With omeprazole, we observed a decrease in positive results in
      ultrarapid urease test and histopathological examination for Helicobacter pylori
      in the antrum, but not in the corpus. CONCLUSION: Omeprazole, used for 7 days can
      lead to negative results in ultrarapid urease test and histopathological
      examination for Helicobacter pylori in the antrum, and should not be employed in
      patients before the endoscopy is performed.

PMID- 11586998
TI  - [Gastroduodenal Crohn's disease - report of 4 cases and review of the
      literature].
AB  - BACKGROUND: Crohn's disease can affect all the gastrointestinal tract, but
      gastroduodenal involvement is rarely seen (0.5 to 13%). OBJECTIVES: Report
      clinical, radiological and endoscopic findings and treatment of four patients
      with gastroduodenal Crohn's disease and review the literature. PATIENTS AND
      METHODS: Four patients (one male of 24 years old three females of 37, 66 and 74
      years old) with epigastric pain, weight loss and low grade fever were referred to
      the University Hospitals of Federal University of Rio de Janeiro and Fluminese
      Federal University. Two had also mild intermittent diarrhea and
      arthritis/arthralgia and the third developed pyloric obstruction and received
      surgical treatment. Anemia was observed in only one (the young female). Barium x
      ray studies showed aphthous ulcers in stomach and duodenum with distal ileum
      lesions and deformity in both. Upper gastrointestinal endoscopy revealed aphthous
      ulcers in stomach and geographic duodenal ulcers. Polypoid lesions and
      serpiginous ulcers within gastric antrum were observed in the young female.
      Colonoscopy was performed in two patients and disclosed an ulcerated ileitis in
      one and ulcerated pancolitis in other. Histopathology findings of biopsy
      specimens were inconclusive (granulomas were not found) and other causes of
      granulomatous disease were ruled out. Corticosteroids and proton pump inhibitors
      were started and two patients had their disease controlled. The other patient
      developed pyloric obstruction and had to be operated. CONCLUSIONS: Gastroduodenal
      Crohn's disease has distinct clinical, therapeutic and prognostic features.
      Advances in endoscopic methods and recognition of new histopathologic criteria
      for diagnosis have revealed an incidence higher than previously reported.

PMID- 11586997
TI  - [Experimental cirrhosis induced by carbon tetrachloride inhalation: adaptation of
      the technique and evaluation of lipid peroxidation].
AB  - BACKGROUND: Long-term administration of carbon tetrachloride is an accepted
      experimental model to produce hepatic fibrosis. Oxidative stress has been
      postulated as a major molecular mechanism involved in carbon tetrachloride
      hepatotoxicity, where the reactive oxygen species play an important role in the
      pathogenesis of liver fibrosis. AIMS: This study was conducted to evaluate the
      effectiveness of an experimental model of hepatic cirrhosis induced by carbon
      tetrachloride inhalation as well as the importance of lipid peroxidation and the
      characteristics of the ascitic fluid in this model. METHODS: At first the hepatic
      histologic findings were assessed using the hematoxilineosin technique in
      different moments of carbon tetrachloride inhalation (5th, 7th, 9th, 12th weeks).
      Later, at the end of 15 weeks of the study the rats were divided in three groups
      (control; control + phenobarbital; and carbon tetrachloride + phenobarbital) for
      lipid peroxidation, ascitic fluid and histologic characteristics evaluation. For
      the lipid peroxidation analysis, thiobarbituric acid and QL techniques were used.
      Cytologic and bacteriologic parameters were analysed in the ascitic fluid.
      RESULTS: Cirrhosis was established in 100% of carbon tetrachloride rats between
      the 12th and 15th weeks with an elevation in the lipid peroxidation carbon
      tetrachloride rats' livers. Ascitic fluid infection was observed in one of seven
      rats who has developed ascites. CONCLUSIONS: The carbon tetrachloride inhalation
      method developed in this study is effective in cirrhosis induction and ascites
      formation, and the carbon tetrachloride cirrhosis physiopathogenesis is probably
      related to the oxidative stress installation.

PMID- 11586999
TI  - [TIPS - Transjugular intrahepatic portosystemic shunt. A review].
AB  - At the present time several therapeutic options are used for the treatment of
      bleeding esophageal varices in patients with portal hypertension. We will review
      the main medical publications on transjugular intrahepatic portosystemic shunt
      (TIPS), a procedure seldom used among us. TIPS works as a portocaval side-to-side
      shunt and decreases the risk of esophageal bleeding through lowering of the
      portal system pressure and a decrease of the portal hepatic pressure gradient.
      TIPS consists in the percutaneous insertion, through the internal jugular vein,
      of a metallic stent under fluoroscopic control in the hepatic parenchyma creating
      a true porta caval communication. There are several studies demonstrating the
      efficacy of TIPS, although only a few of them are randomized and control-matched
      to allow us to conclude that this procedure is safe, efficient and with a good
      cost benefit ratio. In this review, we search for the analysis of the TIPS
      utilization, its techniques, its major indications and complications. TIPS has
      been used in cases of gastroesophageal bleeding that has failed with
      pharmacologic or endoscopic treatment in patients Child-Pugh B and C. It can be
      used also as a bridge for liver transplantation. Others indications for TIPS are
      uncontrolled ascites, hepatic renal syndrome, and hepatic hydrothorax. The main
      early complications of TIPS using are related to the insertion site and hepatic
      encephalopathy and the stent occlusion is the chief late complication.

PMID- 11587000
TI  - VI Congress of the International Xenotransplantation Association. Chicago,
      Illinois, USA. 29 September-3 October 2001. Abstracts.

PMID- 11587001
TI  - Abstracts of the VII Asian-Pacific Symposium on Cardiac Pacing and
      Electrophysiology (APSE). October 13-16, 2001.

PMID- 11587003
TI  - Abstracts from the 7th National Congress of the Italian Association of Neuro
      Oncology (AINO). Turin, Italy, October 29-31, 2001.

PMID- 11587002
TI  - Abstracts from the 14th International Conference on Brain Tumor Research and
      Therapy. Asheville, North Carolina, USA. May 27-30, 2001.

PMID- 11587004
TI  - Abstracts from the 3rd International From Gene to Cure Congress. Amsterdam, The
      Netherlands. April 26-28, 2001.

PMID- 11587005
TI  - Abstracts from the 27th annual meeting of the International Society for Pediatric
      and Adolescent Diabetes (ISPAD). September 19-22, 2001. Siena, Italy.

PMID- 11587006
TI  - Replicating Vectors for Gene Therapy. Abstracts for the Harold W. Siebens
      Conference. 5-7 October 2001. Rochester, Minnesota, USA.

PMID- 11587007
TI  - Abstracts of the 13th National Meeting of the Italian Society for Pediatric
      Endocrinology and Diabetology (SIEDP). Trieste, 10-13 October 2001.

PMID- 11587008
TI  - Evaluation of the woman with postmenopausal bleeding: Society of Radiologists in
      Ultrasound-Sponsored Consensus Conference statement.
AB  - OBJECTIVES: A panel of 14 physicians practicing medicine in the United States
      with expertise in radiology, obstetrics and gynecology, gynecologic oncology,
      hysteroscopy, epidemiology, and pathology was convened by the Society of
      Radiologists in Ultrasound to discuss the role of sonography in women with
      postmenopausal bleeding. Broad objectives of this conference were (1) to advance
      understanding of the utility of different diagnostic techniques for evaluating
      the endometrium in women with postmenopausal bleeding; (2) to formulate useful
      and practical guidelines for evaluation of women with postmenopausal bleeding,
      specifically as it relates to the use of sonography; and (3) to offer suggestions
      for future research projects. SETTING: October 24 and 25, 2000, Washington, DC,
      preceding the annual Society of Radiologists in Ultrasound Advances in Sonography
      conference. PROCEDURE: Specific questions to the panel included the following:
      (1) What are the relative effectiveness and cost-effectiveness of using
      transvaginal sonography versus office (nondirected) endometrial biopsy as the
      initial examination for a woman with postmenopausal bleeding? (2) What are the
      sonographic standards for evaluating a woman with postmenopausal bleeding? (3)
      What are the abnormal sonographic findings in a woman with postmenopausal
      bleeding? (4) When should saline infusion sonohysterography or hysteroscopy be
      used in the evaluation of postmenopausal bleeding? (5) Should the diagnostic
      approach be modified for patients taking hormone replacement medications,
      tamoxifen, or other selective estrogen receptor modulators? CONCLUSIONS:
      Consensus recommendations were used to create an algorithm for evaluating women
      with postmenopausal bleeding. All panelists agreed that because postmenopausal
      bleeding is the most common presenting symptom of endometrial cancer, when
      postmenopausal bleeding occurs, clinical evaluation is indicated. The panelists
      also agreed that either transvaginal sonography or endometrial biopsy could be
      used safely and effectively as the first diagnostic step. Whether sonography or
      endometrial biopsy is used initially depends on the physician's assessment of
      patient risk, the nature of the physician's practice, the availability of high
      quality sonography, and patient preference. Similar sensitivities for detecting
      endometrial carcinoma are reported for transvaginal sonography when an
      endometrial thickness of greater than 5 mm is considered abnormal and for
      endometrial biopsy when "sufficient" tissue is obtained. Currently, with respect
      to mortality, morbidity, and quality-of-life end points, there are insufficient
      data to comment as to which approach is more effective. The conference concluded
      by identifying several important unanswered questions and suggestions that could
      be addressed by future research projects.

PMID- 11587009
TI  - Society of Radiologists in Ultrasound Consensus Conference statement on
      postmenopausal bleeding.

PMID- 11587010
TI  - Is an isolated fetal cardiac echogenic focus an indication for fetal
      echocardiography?
AB  - OBJECTIVE: To determine whether the presence of an isolated fetal cardiac
      echogenic focus should be an indication for fetal echocardiography. METHODS: We
      reviewed our fetal echocardiography and obstetrics databases from January 1992
      through July 1999. The study groups were formulated from patients referred for
      fetal echocardiography. Patients referred for echocardiography because of a
      single isolated fetal cardiac echogenic focus were compared with patients
      referred for other indications. The sensitivity, specificity, and positive and
      negative predictive values were calculated for an isolated echogenic focus as a
      marker for structural cardiac abnormalities as detected by fetal
      echocardiography. RESULTS: Of 10,406 fetuses seen for ultrasonography, 1908 had
      fetal echocardiography. Cardiac abnormalities were identified in 3.4% (65 of
      1908) of the fetuses that had echocardiography. The prevalence of an isolated
      echogenic focus was 2.2% (230 of 10,406) and was the indication in 12.1% (230 of
      1908) of our echocardiograms. Only 1 of the 230 fetuses with an isolated
      echogenic focus had a structural cardiac defect (membranous ventricular septal
      defect). An isolated echogenic focus as a marker for congenital cardiac defects
      resulted in sensitivity and specificity of 1.5% and 87.6%, respectively. The
      positive and negative predictive values were 0.4% and 96.2%, respectively The
      relative risk for an echogenic focus in predicting congenital cardiac defects was
      0.11 (95% confidence interval, 0.02-0.82). CONCLUSIONS: An isolated fetal cardiac
      echogenic focus is not an efficacious marker for congenital cardiac defects. It
      should not be the sole indication for fetal echocardiography.

PMID- 11587011
TI  - Are maternal and sonographic factors associated with the detection of a fetal
      echogenic cardiac focus?
AB  - OBJECTIVE: To evaluate the influence of maternal weight and the orientation of
      the fetal 4-chamber heart view on the detection of a fetal echogenic cardiac
      focus. METHODS: In this nested case-control study, 103 women undergoing anatomic
      surveys at 15 to 22 weeks between January 1, 1997, and June 15, 1999, were
      identified as having an echogenic cardiac focus via our computerized database. A
      control group was selected from among the same group of patients. Data were
      collected from the sonography reports, prenatal records, and sonographic images
      of 4-chamber heart views; maternal characteristics and sonographic details were
      recorded, including the orientation of the 4-chamber view (apical, basilar, and
      right and left lateral). RESULTS: Gravidas in the echogenic cardiac focus group
      were more likely to be of lower weight (68.0 +/- 14.4 versus 72.9 +/- 18.3 kg; P
      = .04), of lower body mass index (25.5 +/- 5.3 versus 27.3 +/- 6.2 kg/m2; P =
      .03), of younger age (24.4 +/- 6.5 versus 26.9 +/- 6.9 years; P = .01), and
      African American or Asian (37.9% versus 27.2% and 9.7% versus 2%; P = .01). Cases
      were scanned at earlier gestational ages (18.9 +/- 1.6 versus 19.5 +/- 1.7 weeks;
      P = .01). The focus group was more likely to have had an apical view of the fetal
      heart taken (80.8% versus 51.4%; P = .0001). Controls were more likely to have
      had a right lateral view taken (44.6% versus 20.8%; P = .002). No significant
      difference was found between groups in terms of any other maternal or sonographic
      variable studied. CONCLUSIONS: The echogenic cardiac focus group was more likely
      to have a lower body mass index and to be scanned with the apical fetal heart
      view. The orientation of the fetal 4-chamber heart view exerted the most
      statistically significant influence on detection rates for the echogenic cardiac
      focus, implying that the more technically facile the sonographic study, the more
      likely an echogenic cardiac focus will be found.

PMID- 11587012
TI  - Isolated sonographic markers for detection of fetal Down syndrome in the second
      trimester of pregnancy.
AB  - OBJECTIVE: To determine whether sonographic "markers" are associated with fetal
      Down syndrome during the second trimester and to estimate the degree of risk of
      individual markers using likelihood ratios. METHODS: Second-trimester (14-20
      weeks) sonographic findings in 186 fetuses with trisomy 21 were compared with a
      control group of 8728 consecutive control fetuses. Six markers were evaluated:
      nuchal thickening, hyperechoic bowel, shortened femur, shortened humerus,
      echogenic intracardiac focus, and renal pyelectasis. RESULTS: Major or structural
      abnormalities were observed in 31 fetuses with trisomy 21 (16.7%) and 53 control
      fetuses (0.6%) (P< .001). Some type of sonographic finding (major abnormality,
      minor marker, or both) was observed in 68.8% of fetuses with trisomy 21 compared
      with 13.6% of control fetuses (P < .001). An isolated minor or "soft" marker was
      the only sonographic finding in 42 (22.6%) of 186 fetuses with trisomy 21
      compared with 987 (11.3%) of 8728 control fetuses (P < .001). Nuchal thickening
      (P < .001; likelihood ratio, 11) and hyperechoic bowel (P < .001; likelihood
      ratio, 6.7) showed the strongest association with trisomy 21 as isolated markers,
      followed by shortened humerus (likelihood ratio, 5.1), echogenic intracardiac
      focus (likelihood ratio, 1.8), shortened femur (likelihood ratio, 1.5), and
      pyelectasis (likelihood ratio, 1.5). Echogenic intracardiac focus was the single
      most common isolated marker in both affected fetuses (7.1%) and control fetuses
      (3.9%) but carried a low risk (P= .046; likelihood ratio, 1.8). CONCLUSIONS: A
      single soft marker is commonly encountered during the second trimester among
      fetuses with trisomy 21. The risk of fetal Down syndrome, reflected by likelihood
      ratios, was determined for 6 individual markers. This information can be combined
      with the a priori risk to estimate the individual patient risk for fetal Down
      syndrome.

PMID- 11587013
TI  - Evaluation and follow-up of fetal hydronephrosis.
AB  - OBJECTIVE: To determine the antenatal course and neonatal follow-up of isolated
      fetal hydronephrosis. METHODS: We reviewed our ultrasonography database from
      January 1989 to June 1999 for all cases of unilateral or bilateral fetal
      hydronephrosis that had at least 1 follow-up ultrasonographic examination. Cases
      were defined as mild, moderate, or severe depending on the renal pelvis
      anteroposterior diameter and gestational age. Data were analyzed using the chi2
      test with the Fisher exact test where appropriate. Medical records were reviewed,
      and telephone interviews were performed to determine which infants received
      follow-up after birth. RESULTS: Of 57,966 ultrasonographic examinations in 20,049
      women during the study period, 393 patients met criteria for evaluation. Of
      these, 347 (88%) had fetuses with mild hydronephrosis. Most of these had complete
      resolution during the pregnancy. Forty patients had fetuses classified as having
      moderate hydronephrosis, and 6 patients had fetuses with severe hydronephrosis.
      Of those classified as moderate hydronephrosis, 15% resolved, 25% improved, 48%
      remained unchanged, and 12% worsened during the pregnancy. There were no cases of
      in utero resolution in the severe group; however, 4 of 6 cases improved to
      moderate or mild, and 2 cases remained unchanged. Of the cases identified
      prenatally, 25 received consultation by a pediatric urologist in the newborn
      period, and 7 of these required surgical intervention. CONCLUSIONS: Our
      population-based data suggest that most cases of mild hydronephrosis will resolve
      before delivery. In contrast, cases of moderate or severe hydronephrosis are less
      likely to have resolution in utero and are more likely to worsen or remain
      unchanged. Of those fetuses with persistent hydronephrosis, only a small number
      required some surgical intervention after birth. This information is useful in
      counseling the patient whose fetus is noted to have isolated hydronephrosis.

PMID- 11587014
TI  - Ultrasonographic evaluation of the cervix: transperineal versus endovaginal
      imaging.
AB  - OBJECTIVE: This study compares transperineal and endovaginal ultrasonography of
      the gravid cervix to evaluate image quality and assess for a systematic
      difference in cervical lengths measured by the 2 techniques. METHODS:
      Transperineal and endovaginal ultrasonography of the cervix was performed on 64
      pregnant women. Two physicians reviewed the images and rated the relative
      diagnostic value of the techniques for assessing the cervix and for evaluating
      for placenta previa. Cervical length was measured prospectively in both
      techniques. Data were analyzed to determine if there is a systematic difference
      in length using the 2 approaches and if length differences are dependent on
      gestational age. RESULTS: There was a strong reviewer preference for endovaginal
      ultrasonographic images over transperineal images for both assessing the cervix
      (P< .001) and evaluating for placenta previa (P< .001). Despite this,
      transperineal and endovaginal ultrasonographic images were frequently rated as
      similar in diagnostic quality by both reviewers for depicting the cervix (35.9%
      of patients) and evaluating for placenta previa (57.8% of patients). The mean
      length of the cervix was slightly shorter at transperineal ultrasonography (28.4
      mm) than at endovaginal ultrasonography (30.1 mm). When cervical lengths were
      subdivided by gestational age, however, a significant length discrepancy was
      found only in the 14- to 20-week gestational age range. In this age range, mean
      cervical length at transperineal ultrasonography (28.6 mm) averaged 5.5 mm less
      than at endovaginal ultrasonography (34.1 mm). CONCLUSIONS: Both transperineal
      and endovaginal ultrasonography can provide satisfactory images of the cervix,
      but endovaginal images are frequently superior to transperineal images.
      Endovaginal ultrasonography should be considered the optimal method for imaging
      the cervix in most situations. Transabdominal or transperineal ultrasonography
      can also be used, but if the cervix is not adequately depicted from these
      perspectives, endovaginal ultrasonography is indicated. Transperineal
      measurements of cervical length can be significantly shorter than endovaginal
      measurements, particularly before 20 weeks; therefore, short cervical lengths
      documented at transperineal ultrasonography before 20 weeks should be confirmed
      by endovaginal ultrasonography.

PMID- 11587015
TI  - Ovarian and adnexal torsion: spectrum of sonographic findings with pathologic
      correlation.
AB  - OBJECTIVE: To determine the spectrum of sonographic findings on gray scale and
      color Doppler sonography in a series of pathologically proven cases of ovarian
      and adnexal torsion. METHODS: The study population included 15 patients with
      surgical confirmation of ovarian or adnexal torsion, or both, who underwent
      sonographic examination before surgery. All sonograms were reviewed
      retrospectively. RESULTS: Gray scale abnormalities included the following:
      complex masses in 11 (73%) of 15 patients, cystic masses in 3 (20%), and a solid
      mass in 1 (7%). Cul-de-sac fluid was present in 13 (87%) of 15 patients. Adnexal
      neoplasms were present in 4 (27%) of 15 (1 granulosa cell tumor and 3 dermoid
      cysts) on pathologic examination. Doppler findings were abnormal in 14 (93%) of
      15 patients and normal in 1 (7%). Abnormal Doppler findings included no arterial
      and no venous flow in 6 (40%) of 15, decreased venous flow with no arterial flow
      in 5 (33%), decreased venous flow and decreased arterial flow in 2 (13%), and
      decreased arterial flow with no venous flow in 1 (7%). Small amounts of cul-de
      sac fluid were present in 13 (87%) of 15 patients. CONCLUSIONS: The diagnosis of
      ovarian and adnexal torsion remains challenging. It cannot be based solely on the
      absence or presence of flow on color Doppler sonography, because the presence of
      arterial or venous flow does not exclude the diagnosis of adnexal torsion.
      Comparison with the morphologic appearance and flow patterns of the contralateral
      ovary will aid in diagnosis.

PMID- 11587016
TI  - Differential diagnosis of solid breast lesions: contribution of Doppler studies
      to mammography and gray scale imaging.
AB  - OBJECTIVE: To assess the role of Doppler sonography when used in conjunction with
      mammography and gray scale sonography in differentiating solid breast lesions and
      to find out whether lesion size is a limiting factor for Doppler evaluation.
      METHODS: One hundred twelve lesions (70 malignant and 42 benign) detected with
      mammography and sonography were prospectively examined with color, power, and
      pulsed Doppler sonography. Vascularity was analyzed morphologically (vessel
      location, form, and color tone) and semiquantitatively (by spectral indices) to
      determine the valuable diagnostic flow characteristics. The lesions were
      classified by 2 observers as benign or malignant on the basis of each diagnostic
      technique (namely, a combination of mammography and gray scale sonography,
      presence or absence of blood flow, morphologic flow analysis, and spectral flow
      analysis). The results were compared with the histologic diagnosis in 105 lesions
      and with the clinical and radiologic diagnosis after at least 2 years of follow
      up in 7 lesions. RESULTS: The sensitivity and specificity of the mammography-gray
      scale sonography combination were 98.6% and 76.2%, respectively. Neither
      morphologic nor spectral Doppler analysis proved to be successful on its own,
      however, information obtained from investigated morphologic and spectral flow
      features increased the specificity of mammography and gray scale sonography for
      lesions 10 mm and smaller (from 88.9% to 100%) and those larger than 10 mm (from
      70% to 96.6%). CONCLUSIONS: Our data show that Doppler sonography is a beneficial
      adjunct to mammography and gray scale sonography for solid breast lesions 10 mm
      and smaller and those larger than 10 mm.

PMID- 11587017
TI  - Saline infusion sonohysterography in nonpregnant women with previous cesarean
      delivery: the "niche" in the scar.
AB  - OBJECTIVE: To apply an existing diagnostic imaging test (saline infusion
      sonohysterography) to characterize the "filling defect" of a previous cervical
      cesarean delivery scar in the nonpregnant uterus. METHODS: Forty-four patients
      with histories of cesarean delivery who underwent saline infusion
      sonohysterography for a variety of gynecologic indications were included. During
      the procedure, the area below the bladder recess was examined using transvaginal
      sonography. A filling defect or "niche" was defined as a triangular anechoic
      structure at the presumed site of a previous cesarean delivery scar. The depth of
      the niche was measured. Uterine size, the presence of fibroids and polyps, and
      the number of previous cesarean deliveries were noted. RESULTS: All patients had
      a niche indenting the anterior uterine-cervical wall. The mean +/- SD depth of
      the niche was 6.17 +/- 3.6 mm. There was no correlation between the number of
      cesarean deliveries and the depth of the niche. Thirty-six percent of our
      patients had fibroids, and 18% had endometrial polyps. CONCLUSION: Saline
      infusion sonohysterography was able to detect filling defects in women who
      previously had cesarean deliveries. We hope that by focusing our attention on the
      transvaginal sonographic appearance of the detectable uterine scar (niche) with
      or without the use of saline infusion sonohysterography in the nonpregnant
      uterus, it will train our eyes to look for the scar in the pregnant uterus. In
      addition, our study patients had a high prevalence of abnormal uterine bleeding.
      The role of the cesarean delivery scar in women with unscheduled bleeding needs
      to be further evaluated.

PMID- 11587018
TI  - Fetus acardius: two- and three-dimensional ultrasonographic diagnoses.
AB  - OBJECTIVE: To determine whether ultrasonographic detection of acardiac fetuses
      and diagnostic accuracy of related malformations improve with complementary use
      of two-dimensional ultrasonography, three-dimensional ultrasonography, and
      Doppler scanning. METHODS: Three pregnant women with multifetal gestations who
      were found to have discordant fetuses on initial two-dimensional ultrasonographic
      scanning were subsequently scanned with three-dimensional ultrasonography and
      color Doppler ultrasonography. RESULTS: Although the possibility of acardiac
      fetuses was entertained in all cases after two-dimensional ultrasonographic
      scanning, the diagnosis was confirmed, and the accuracy and extent of fetal
      malformations were established with three-dimensional ultrasonography and color
      Doppler scanning. Two of the women had twin gestations, and the third woman had a
      triplet gestation. Among the women with twin gestations, 1 donor twin had no
      abnormalities, and the other donor twin had a diagnosis of arthrogryposis and
      gastroschisis. The woman with triplets had 1 acardiac fetus; the donor fetus was
      anencephalic; and the third fetus had alobar holoprosencephaly. CONCLUSIONS:
      Complementary use of two-dimensional ultrasonography, three-dimensional
      ultrasonography, and color Doppler scanning improves diagnostic accuracy and the
      ability to evaluate the extent and severity of organ compromise in pregnancies
      complicated by acardiac fetuses.

PMID- 11587019
TI  - Diagnosis of extrarenal arteriovenous fistula by color Doppler flow imaging.

PMID- 11587021
TI  - Trisomy 13 appearing as a mimic of a triploid partial mole.

PMID- 11587020
TI  - Congenital chloride diarrhea: antenatal ultrasonographic findings in siblings.

PMID- 11587022
TI  - Resolution of hydrops fetalis despite persistent fetal tachycardia.

PMID- 11587023
TI  - Child sexual abuse and human papillomavirus infection.

PMID- 11587024
TI  - [99th Meeting of the German Society of Ophthalmology. Berlin, 29 September-2
      October 2001. Abstracts].

PMID- 11587026
TI  - American Association for the Study of Liver Diseases 52nd annual meeting.
      November 9-13, 2001. Dallas, Texas, USA. Abstracts.

PMID- 11587025
TI  - [7th Annual Congress of the German Society of Radiation Oncology. Hamburg, 8-11
      September 2001. Abstracts].

PMID- 11587027
TI  - [XXIV National Meeting of the Spanish Society of Internal Medicine. Madrid, 27-29
      June 2001. Abstracts].

PMID- 11587028
TI  - Pulmonary vasoreactivity in PPH.

PMID- 11587029
TI  - Coronary artery revascularization in patients with sustained ventricular
      arrhythmias in the chronic phase of a myocardial infarction.

PMID- 11587030
TI  - Management of anomalous coronary artery.

PMID- 11587031
TI  - Major coronary artery anomalies in the pediatric population.

PMID- 11587032
TI  - Acute ethanol exposure fails to elicit preconditioning-like protection in in situ
      rabbit hearts because of its continued presence during ischemia.

PMID- 11587033
TI  - Patient management guided by viability imaging.

PMID- 11587035
TI  - [54th annual meeting of the Japanese Association for Thoracic Surgery. Osaka,
      Japan. October 3-5, 2001. Abstracts].

PMID- 11587034
TI  - Periodontal disease and risk of myocardial infarction.

PMID- 11587036
TI  - Isocyanate-terminated urethane prepolymer as bioadhesive material: evaluation of
      bioadhesion and biocompatibility, in vitro and in vivo assays.
AB  - Attempts have been made to evaluate the degree of bioadhesion and
      biocompatibility of a synthesized urethane prepolymer with specially tailored
      microstructure. Wetting behaviour and extent of interfacial adhesion of the
      prepared prepolymer towards biological substrates were examined by in vitro
      methods. The former was carried out by measuring the contact angle between drops
      of the prepolymer liquid and a biological surface, while the latter was
      determined from the force between the prepolymer and tissue model or mucus. The
      obtained results exhibited good tissue wettability and bioadhesion by the
      prepolymer. Preliminary evaluation of biocompatibility for the uncatalytically
      cured prepolymer films was performed by cytotoxicity and histotoxicity
      experiments. Results showed a significant growth for the adhered L929 fibroblast
      cells within a period of 5 days incubation. Also, no severe inflammatory tissue
      response towards the samples implanted in rabbit for 16 weeks was seen. These
      observations can support the potentiality of the designed urethane prepolymer to
      be applied as hemostatic agent.

PMID- 11587037
TI  - Plasma lithography--thin-film patterning of polymeric biomaterials by RF plasma
      polymerization I: Surface preparation and analysis.
AB  - Plasma lithography, combining plasma deposition with photolithography, is
      described as a versatile method to manufacture all-polymeric substrates with thin
      film patterns for applications in biomedical engineering. Patterns of a
      hydrophobic fluorocarbon plasma polymer with feature sizes between 5 and 100
      microm were deposited on a base substrate in a lift-off process: an intermediate
      tetraglyme plasma polymer layer provides non-fouling properties to the base
      substrate. Careful analysis of critical process parameters identified the narrow
      window of process conditions that led to the formation of functional surface
      patterns. High pattern fidelity, aspect ratios, and resolution of the patterns
      are demonstrated by atomic force microscopy. Electron spectroscopy for chemical
      analysis (ESCA) and secondary ion mass spectroscopy (SIMS) were used to
      characterize the surfaces, showing good retention of the original chemical
      structure of the pattern components throughout the process. SIMS imaging was used
      for specific chemical imaging of the components. Potential applications for the
      patterned polymer films, e.g., for studying cell behavior in vitro in dependence
      of shape and size of adhering cells, are discussed.

PMID- 11587038
TI  - Plasma lithography--thin-film patterning of polymers by RF plasma polymerization
      II: Study of differential binding using adsorption probes.
AB  - In this study we present methods to physico-chemically modify micropatterned cell
      culture substrates that were manufactured using plasma lithography to incorporate
      affinity structures for specific cell binding. The surfaces consist of a pattern
      of a fluorocarbon plasma polymer with feature sizes between 5 and 100 microm on a
      background of a non-fouling tetraglyme (tetraethylene glycol dimethyl ether)
      plasma polymer. The tetraglyme polymer blocks virtually all non-specific binding
      of proteins, and it is non-adhesive for a fluorocarbon-polyethylene glycol (FC
      PEG) surfactant designed to act as a 'hydrophobic anchor' for peptides. The
      surfactant shows a strong affinity for the fluorocarbon polymer pattern, thus
      enabling us to form a pattern of the surfactant-conjugated peptide. To verify
      this, we have synthesized a conjugate between histamine (as a model for a more
      complex peptide) and a commercially available FC-PEG surfactant. Disuccinimidyl
      carbonate was used to activate the terminal -OH group of the polyethylene glycol
      headgroup for the reaction with the amine-containing molecule. Affinity pattern
      formation can easily be achieved by immersion of the patterned substrates in a
      solution of the peptide-surfactant conjugate. Time of flight secondary ion mass
      spectroscopy in the imaging mode was used to verify that the surfactant localizes
      on the pattern, while the background remains bare. A model protein, bovine serum
      albumin, showed the same behavior. This suggests that these surfaces can be used
      for the formation of patterns of cell-adhesive proteins. These substrates will be
      used to investigate the influence of the cell size and shape of vascular smooth
      muscle cells on their physiology.

PMID- 11587040
TI  - A decrease in Sendai virus infection potency by interactions with cationic thermo
      responsive polymers.
AB  - Three types of synthetic cationic polymers were incubated with Sendai virus
      (HVJ), and virus infection of Rhesus monkey kidney cells, LLCMK2, was measured by
      the plaque assay method. One composition poly(N-isopropylacrylamide-co-N,N
      dimethylaminopropyl acrylamide-co-butylmethacrylate) of (P(IP-27DA-16BM)) showed
      substantial decreases in the infection potency of the virus over a wide range of
      polymer concentrations. This polymer expressed a significant virus titer decrease
      even at a very low concentration (2 x 10(-4) wt%), and its virus titer reduction
      was found to be incubation temperature-dependent. As the virus was incubated with
      this polymer above the phase transition temperature of this polymer over a long
      period, the virus titer reduction was larger. Selectivity to the virus titer
      reduction in comparison with cytotoxicity to LLCMK2 cells was evaluated. This
      P(IP-27DA-16BM) polymer was revealed to possess a higher selectivity to virus
      reduction than sodium dodecyl sulfate. This indicates the feasibility of this
      polymer for a virus-specific inactivating agent.

PMID- 11587041
TI  - Effects of ethylene oxide gas sterilization on physical properties of poly(L
      lactide)-poly(ethylene glycol)-poly(L-lactide) microspheres.
AB  - The aggregation of poly(alpha-hydroxy acid) microspheres during ethylene oxide
      (EO) gas sterilization makes it difficult for the microspheres to be used in
      clinical applications. In this study, six kinds of PLLA-PEG-PLLA triblock
      copolymers (TriPLE) were synthesized with various composition ratios of PEG/PLLA
      in the range of 0.012 to 0.103. TriPLE microspheres were prepared by the oil-in
      water emulsion method. TriPLE microspheres were characterized by using 1H-NMR,
      gel permeation chromatography (GPC), and differential scanning calorimetry (DSC).
      After sterilization by EO gas at 55 degrees C, the microspheres were analyzed by
      scanning electron microscope (SEM), laser diffractometry, standard sieves, X-ray
      diffraction (XRD), GPC, and DSC. When the composition ratio of PEG/PLLA was above
      0.02, the initial crystallinity of TriPLE in microspheres was as high as 50%, and
      the microspheres were suitable to be sterilized by EO gas. On the other hand,
      TriPLE microspheres, which had composition ratios of PEG/PLLA below 0.02, had low
      initial crystallinities of about 30%, and aggregated during EO gas sterilization.
      For these microspheres, crystallinity increased up to 50% during the
      sterilization, whereas other TriPLE microspheres did not show any changes in
      crystallinity. Therefore, the aggregation of TriPLE microspheres during EO gas
      sterilization was markedly reduced as the initial crystallinity of TriPLE in the
      microspheres was increased.

PMID- 11587039
TI  - Hepatocyte attachment onto thermosensitive poly(N-isopropylacrylamide-co-N-p
      vinylbenzyl-O-beta-D-galactopyranosyl-(1 --> 4)-D-gluconamide).
AB  - Temperature sensitive poly(N-isopropylacrylamide) (PIPAAM) was incorporated into
      hepatocyte-recognizable poly[N-p-vinylbenzyl-O-beta-D-galactopyranosyl-(1 --> 4)
      D-gluconamide] (PVLA) for thermal modulating of hepatocyte attachment. The
      copolymer, poly(N-isopropylacrylamide-co-N-p-vinylbenzyl-O-beta-D
      galactopyranosyl-(1 --> 4)-D-gluconamide) (abbreviated as [P(IPAAM-co-VLA)]
      (PIPAAM/PVLA = 9/1 in mol%) exhibited lower critical solution temperature (LCST)
      at 34 degrees C and also showed very good hepatocytes-recognizablility through
      the specific interaction between asialoglycoprotein receptors on the cell
      surfaces and galactose moiety of the copolymer. The cells attached on this
      copolymer were easily detached by lowering the temperature below the LCST of the
      copolymer. Morphological damage of the detached cell was not observed.

PMID- 11587042
TI  - The transport of octamethylcyclotetrasiloxane (D4) and polydimethylsiloxane
      (PDMS) in lightly cross-linked silicone rubber.
AB  - The transport of octamethylcyclotetrasiloxane (D4), one of the major constituents
      of silicone fluids and rubbers, and low viscosity polydimethylsiloxane oil into a
      silica filled cross-linked silicone elastomeric rubber was measured as a function
      of temperature, cross-link density of the rubber, and concentration of the D4 in
      methanol solution. A small amount of material, approximately 3 wt%, is extracted
      from the rubber with hexane. The extraction process has a large effect upon D4
      solubility in the rubber, increasing from approximately 160 to 180 wt% after
      extraction. The heats of solution for both penetrants into the rubber are
      essentially zero and the activation energies for diffusion are small,
      approximately 8 and 15 kJ molt(-1) for D4 and PDMS, respectively. The diffusion
      process is Fickian and the diffusion coefficient of D4 into silicone/silica
      rubbers is essentially independent of concentration over the concentration
      investigated, i.e. from 1 to 100 vol% D4 in methanol. The permeability, i.e. the
      product of the diffusion coefficient and the solubility, decreases rapidly for D4
      concentrations less than 50 vol% (0.1 mol fraction). This suggests that the
      permeation of D4 out of any encapsulation device, such as a silicone breast
      implant, is linearly dependent upon the concentration of D4 in the prosthesis.
      Swelling is isotropic and was measured by dimensional changes in rectangular
      samples and correlates well with the volume of D4 sorbed.

PMID- 11587043
TI  - Adhesion and proliferation of rat vascular smooth muscle cells (VSMC) on
      polyethylene implanted with O+ and C+ ions.
AB  - Polyethylene was implanted with 30-keV oxygen (PE/O+) or 23-keV carbon ions
      (PE/C+) at 10(13) to 5 x 10(15) ions cm(-2) doses in order to improve the
      adhesion of vascular smooth muscle cell (VSMC) to the polymer surface in vitro
      because of its oxidation and carbon-enrichment. The concentration of -CO- groups
      in the PE/O+ and PE/C+ samples increased only up to doses of 3 x 10(14) and
      10(15) ions cm(-2), respectively, and then declined. At the same time, the
      concentration of these groups, measured at a dose of 3 x 10(14) ions cm(-2), was
      higher in PE/O+ than in PE/C+ samples. Similarly, the number of initially
      adhering rat VSMC (24 h after seeding) increased only up to a dose of 3 x 10(13)
      and 10(15) ions cm(-2) on PE/O+ and PE/C+ samples, respectively. In addition,
      between doses of 10(13) and 10(14) ions cm(-2), this number was about two to
      three times higher on PE/O+ samples. On the other hand, the surface wettability
      increased proportionally to the implanted ion dose, especially above a dose of
      10(14) ions cm(-2). Thus, the number of initially-adhered cells appeared to be
      positively correlated with the amount of the oxygen group present at the polymer
      surface rather than with the surface wettability. The higher cell adhesion was
      accompanied by adsorption of fluorescent dye-conjugated collagen IV in larger
      amounts. The highest numbers of initially-adhered cells were usually associated
      with the lowest rates of subsequent proliferation (measured by the doubling time,
      BrdU labelling and M

PMID- 11587044
TI  - The WHO Multinational Study of Vascular Disease in Diabetes.

PMID- 11587045
TI  - Mortality and causes of death in the WHO Multinational Study of Vascular Disease
      in Diabetes.
AB  - AIMS/HYPOTHESIS: We aimed to examine the mortality rates, excess mortality and
      causes of death in diabetic patients from ten centres throughout the world.
      METHODS: A mortality follow-up of 4713 WHO Multinational Study of Vascular
      Disease in Diabetes (WHO MSVDD) participants from ten centres was carried out,
      causes of death were ascertained and age-adjusted mortality rates were calculated
      by centre, sex and type of diabetes. Excess mortality, compared with the
      background population, was assessed in terms of standardised mortality ratios
      (SMRs) for each of the 10 cohorts. RESULTS: Cardiovascular disease was the most
      common underlying cause of death, accounting for 44 % of deaths in Type I
      (insulin-dependent) diabetes mellitus and 52 % of deaths in Type II (non-insulin
      dependent) diabetes mellitus. Renal disease accounted for 21% of deaths in Type I
      diabetes and 11% in Type II diabetes. For Type I diabetes, all-cause mortality
      rates were highest in Berlin men and Warsaw women, and lowest in London men and
      Zagreb women. For Type II diabetes, rates were highest in Warsaw men and Oklahoma
      women and lowest in Tokyo men and women. Age adjusted mortality rates and SMRs
      were generally higher in patients with Type I diabetes compared with those with
      Type II diabetes. Men and women in the Tokyo cohort had a very low excess
      mortality when compared with the background population.
      CONCLUSION/INTERPRETATION: This study confirms the importance of cardiovascular
      disease as the major cause of death in people with both types of diabetes. The
      low excess mortality in the Japanese cohort could have implications for the
      possible reduction of the burden of mortality associated with diabetes in other
      parts of the world.

PMID- 11587046
TI  - The appearance of retinopathy and progression to proliferative retinopathy: the
      WHO Multinational Study of Vascular Disease in Diabetes.
AB  - AIMS/HYPOTHESIS: We aimed to estimate incidences of any retinopathy and
      proliferative diabetic retinopathy (PDR) by direct ophthalmoscopy and relate them
      to baseline risk factors in re-examined diabetic survivors from 10 centres of the
      WHO Multinational Study of Vascular Disease in Diabetes. METHODS: After a mean
      follow-up of 8.4years (11.7 years in Oklahoma), 2877 (71.6%) survivors were
      resubmitted to standardised direct ophthalmoscopy as at baseline. The presence of
      any retinopathy and PDR were recorded at each centre and their incidence
      estimated in those without retinopathy and PDR at baseline. The independent
      associations of these incidences with baseline risk factors are expressed as odds
      ratios derived from multiple logistic regression analyses, within individual
      centres (which included fasting plasma glucose in 8 and triglyceride in 5) and in
      pooled data. RESULTS: Of the 4662 original patients, 465 (10.4%) of those without
      and 77 (43.0%) of those with baseline PDR had died (p < 0.001). Any retinopathy
      was newly reported at follow-up in 47.7 % and PDR in 9.7 % of those free of them
      at baseline, with reported incidences varying substantially among centres.
      Incident retinopathy appeared earlier in the known course of diabetes but
      incidence rates rose more slowly with duration in patients with Type II (non
      insulin-dependent) diabetes mellitus than in those with Type I (insulin
      dependent) diabetes mellitus. In pooled data and in some individual centres, any
      retinopathy incidence gave significantly positive odds ratios with age, diabetes
      duration, systolic pressure, plasma cholesterol, BMI, insulin treatment and
      proteinuria, and with fasting plasma glucose in the centres where it was
      measured. Positive odds ratios for PDR were similarly obtained for age, duration,
      insulin treatment, cholesterol, proteinuria and fasting glycaemia. Smoking status
      odds ratios were negative for both outcomes. CONCLUSION/INTERPRETATION: Incidence
      of ophthalmoscopically ascertained any retinopathy varied about twofold and of
      PDR about threefold among centres. Although, in part attributable to differences
      between observers, variation in incidence in all centres and in some cases within
      centres was associated with a number of baseline risk factors. Such associations
      are not likely due to observer variation or selection biases and emerged despite
      the imprecision of clinical ophthalmoscopy. Improved detection and control of
      these risk factors should reduce the impact of diabetic retinopathy and its
      consequences.

PMID- 11587047
TI  - Follow-up of the WHO Multinational Study of Vascular Disease in Diabetes: general
      description and morbidity.
AB  - AIMS: The incidence of retinal, renal and cardiovascular complications and their
      relation to baseline risk factors was documented in this follow-up study of 10 of
      the 14 original centres of the WHO Multinational Study of Vascular Disease in
      Diabetes (WHO MSVDD). METHODS: The incidence of specified items of vascular
      disease and some associated risk factors was ascertained after 7 to 9 years (11
      12 years in Oklahoma, USA) follow-up, re-using baseline examination methodology
      in 3165 patients (66.9 %) and, through secondary information in 717 (15.2%) of
      the 4729 original patients, of whom 540 (11.4%) had died and 307 (6.5 %) were
      untraceable. RESULTS: During follow-up, approximately one third of the patients
      developed hypertension and one third started insulin. Coronary heart disease
      incidence varied 10 to 20-fold among centres as did limb amputation rates. Inter
      centre differences in incident retinopathy and severe visual impairment were
      smaller but incident clinical proteinuria and renal failure varied markedly.
      Vascular disease incidence of all categories was high in Native Americans though
      coronary heart disease incidence was relatively low in Pima Indians and
      absolutely low in Hong Kong and Tokyo patients. Specific vascular events and
      their relation with baseline risk factors are analysed in accompanying papers,
      summarised in the Epilogue. CONCLUSION/INTERPRETATION: These 10 centres reported
      very different incidence rates of vascular complications. Observer variation,
      selection biases and competing causes of mortality contributed to these
      differences but their validity is supported by the more objective outcome
      indicators. The following papers also suggest that baseline factors such as
      raised arterial pressure, cholesterol and fasting glucose (in the centres where
      it was measured) were important and potentially reversible predictors of risk.

PMID- 11587048
TI  - The incidence of visual impairment and its determinants in the WHO Multinational
      Study of Vascular Disease in Diabetes.
AB  - AIMS/HYPOTHESIS: Incidence of severe visual impairment and the ultimate
      prevalence of all grades of impairment were estimated in the 10 centres of the
      WHO Multinational Study of Vascular Disease in Diabetes (WHO MSVDD) participating
      in the follow-up. METHODS: Visual function was ascertained at follow-up in 2994
      (77.9 %) of the 3845 eligible participating survivors of the 4709 originally
      recruited for the WHO MSVDD using the same baseline enquiry method. The
      associations between incident severe visual impairment, follow-up prevalence of
      all grades of impairment and baseline risk factors were examined by univariate
      and stepwise multiple logistic regression analysis. RESULTS: Overall, 8.4 year
      incidence of severe visual impairment was 1.94 % and showed statistically
      significant univariate correlations with age at diagnosis, diabetes duration,
      systolic blood pressure, fasting blood glucose and cholesterol, insulin treatment
      and strongly with baseline retinopathy. Baseline retinopathy, systolic pressure
      and cholesterol were statistically significant in multivariable analysis.
      Differences between centres (0.3% to 3.45%) were not significant. Ultimate
      prevalence of all grades of impairment differed between centres and within almost
      all of them was correlated in multivariable analysis with baseline retinopathy
      and proteinuria. CONCLUSION/INTERPRETATION: Comparisons of incident severe visual
      impairment between centres are restricted by selective mortality, low incidence
      rates and relatively small numbers in each centre but before retinopathy,
      baseline systolic pressure and cholesterol predicted severe visual impairment.
      Follow-up prevalence of all degrees of impairment varied among centres and were
      associated with prior retinopathy and renal disease at baseline.

PMID- 11587049
TI  - Increased urinary albumin excretion and its associations in the WHO Multinational
      Study of Vascular Disease in Diabetes.
AB  - AIM/HYPOTHESIS: We aimed to determine variations in the prevalence of increased
      urinary albumin excretion, associated risk factors and complications in patients
      with diabetes participating in the WHO Multinational Study of Vascular Disease in
      Diabetes follow-up. METHODS: Urinary albumin to urinary creatinine ratios were
      measured centrally in 2,033 of the 2,550 (79.7%) re-examined patients from eight
      centres in seven countries and the frequency of microalbuminuria and
      macroalbuminuria and their associations with risk factors and complications were
      examined. RESULTS: Macroalbuminuria prevalence (overall 15.6%) varied tenfold (3
      37%) among centres, was higher in American Indian and Asian centres and not
      clearly related to type of diabetes. Microalbuminuria (overall 19.7 %) varied
      less (12-31%). Increased albumin excretion was related overall to baseline
      fasting plasma glucose in the pooled group in whom it was measured and to
      increased arterial pressure, insulin use, coronary heart disease, lower extremity
      amputation, retinopathy and stroke in most centres. CONCLUSION/INTERPRETATION:
      Centres varied widely in the prevalence of increased albumin excretion but
      associations with risk factors and vascular complications were generally similar
      in most centres and in both major types of diabetes with ethnic and genetic
      differences probably contributing.

PMID- 11587050
TI  - Risk factors for renal failure: the WHO Mulinational Study of Vascular Disease in
      Diabetes.
AB  - AIMS/HYPOTHESIS: We aimed to examine risk factors for, and differences in, renal
      failure in diabetic patients from 10 centres. METHODS: Risk factors for renal
      failure were examined in 3,558 diabetic patients who did not have renal disease
      at baseline in the WHO Multinational Study of Vascular Disease in Diabetes (WHO
      MSVDD). RESULTS: In 959 subjects with Type I (insulin-dependent) diabetes
      mellitus and 2,559 with Type II (non-insulin-dependent) diabetes mellitus, the
      average follow-up was 8.4 years (+/- 2.7). By the end of the follow-up period 53
      patients in the Type I diabetic group and 134 patients in the Type II diabetic
      group had developed renal failure (incidence rate 6.3:1,000 person years).
      Increasing age and duration of diabetes were associated with renal failure in
      Type II and Type I diabetes. In Type II diabetes duration of diabetes was a more
      important risk factor than age. In both Type I and Type II diabetic retinopathy
      and proteinuria were strongly associated with renal failure. Systolic blood
      pressure was associated with renal failure in Type I but not in Type II diabetic
      patients. ECG abnormalities at baseline, self-reported smoking and cholesterol
      were not associated with renal failure. Triglycerides were measured in a subset
      of centres. Among those with Type II, but not Type I diabetes, triglycerides were
      associated with renal failure independently of systolic blood pressure,
      proteinuria or retinopathy. In Type II diabetes fasting plasma glucose was
      associated with renal failure independently of other risk factors.
      CONCLUSION/INTERPRETATION: We have confirmed the role of proteinuria and
      retinopathy as markers of renal failure and the importance of hyperglycaemia in
      renal failure in Type I and Type II diabetes. Plasma triglycerides seem to be an
      important predictor of renal failure in Type II diabetes. In Type I diabetes
      systolic blood pressure is an important predictor of renal failure.

PMID- 11587051
TI  - Risk factors for cardiovascular mortality and morbidity: the WHO Mutinational
      Study of Vascular Disease in Diabetes.
AB  - AIMS/HYPOTHESIS: We aimed to examine the associations between classic
      cardiovascular risk factors and diabetes specific factors and the incidence of
      fatal and non-fatal end-points in a large cohort of diabetic patients. METHODS: A
      cohort of 4,743 diabetic patients participating in the WHO Multinational Study of
      Vascular Disease in Diabetes (WHO MSVDD) has been followed up for about 12 years
      and the incidence of fatal and non-fatal cardiovascular disease outcomes
      assessed. RESULTS: The importance of blood pressure, serum cholesterol and
      proteinuria as predictors for cardiovascular disease mortality, fatal and non
      fatal myocardial infarction and stroke is confirmed for patients with Type I
      (insulin-dependent) and Type II (non-insulin-dependent diabetes mellitus. Serum
      triglyceride was associated with cardiovascular disease death in Type II diabetes
      and in women with Type I diabetes and with MI incidence in Type II diabetes and
      stroke in Type II diabetic women. Fasting plasma glucose was associated with
      cardiovascular disease death, incidence of myocardial infarction and stroke in
      Type II diabetes only. In Type II diabetes, multivariate analysis confirmed that
      fasting plasma glucose was related to cardiovascular disease mortality
      independent of other risk factors. The independent relation of triglyceride to
      cardiovascular disease death was statistically significant only for Type II
      diabetic men. The presence of retinopathy was related to cardiovascular disease
      death and incidence of myocardial infarction in both types of diabetes and to
      stroke in Type II diabetes. CONCLUSION/INTERPRETATION: This large cohort study
      shows that the assessment of cardiovascular disease risk in diabetes must include
      'diabetes-related' variables such as glycaemic control, proteinuria and
      retinopathy, as well as the classic risk factors, blood pressure, smoking and
      dyslipidaemia. [Diabetologia

PMID- 11587052
TI  - Risk factors, ethnic differences and mortality associated with lower-extremity
      gangrene and amputation in diabetes. The WHO Multinational Study of Vascular
      Disease in Diabetes.
AB  - AIMS/HYPOTHESIS: We aimed to examine geographic differences, risk factors and
      mortality associated with amputation. METHODS: Data from 10 of the original 14
      centres of the WHO Multinational Study of Vascular Disease in Diabetes were used.
      This included 3443 men and women aged 35 to 55 years at baseline. RESULTS:
      Incidences of amputation, adjusted for sex and duration in Type I (insulin
      dependent) diabetes mellitus, were 31.0, 8.2, 3.5 and 1.0 per 1,000 person years
      in the American Indian, Cuban, European and East Asian centres respectively. In
      Type II (non-insulin-dependent) diabetes mellitus, incidences of amputation were
      9.7, 2.0, 2.5 and 0.7 per 1000 person years in the American Indian, Cuban,
      European and East Asian centres respectively. Key risk factors for amputation
      included glucose, triglyceride, and retinopathy, and were similar for American
      Indians and Europeans. The age, duration and sex adjusted relative risk for
      amputation in American Indians compared with Europeans was 11.48 (95% CI 3.56,
      36.98) in Type I diabetes and 3.86 (95 % CI 2.36, 6.32) in Type II diabetes.
      Adjusting for heart disease, retinopathy, proteinuria, glucose, blood pressure
      and triglyceride attenuated these relative risks to 10.83 (95 % CI 3.20, 36.65)
      and 3.15 (1.91, 5.20) in Type I and Type II diabetes respectively. Amputation
      doubled mortality rates in all groups. CONCLUSION/INTERPRETATION: Vascular
      complications and their risk factors are themselves risk factors for amputation
      in both Type I and Type II diabetes and are common to several geographical
      regions worldwide. However, reasons for differences between geographical regions
      and the degree to which different health care systems could be responsible is not
      clear.

PMID- 11587053
TI  - An analysis of serial Minnesota ECG code changes in the London cohort of the WHO
      Multinational Study of Vascular Disease in Diabetes.
AB  - AIMS/HYPOTHESIS: Deterioration and improvement in the electrocardiogram are
      important outcomes in cardiovascular disease progression assessment. We used a
      sample of serial records from the WHO Multinational Study of Vascular Disease in
      Diabetes (WHO MSVDD) to assess Minnesota coding variability. METHODS: A
      constructed subsample of 118 of the 352 paired (baseline and follow-up) and
      previously Minnesota-coded ECG records from the London cohort was randomised and
      re-read independently of the first code (respectively 11 and 0.5 years later) by
      the same two coders. Detailed Minnesota codes were summary coded into groups 1
      (CHD unlikely), 2 and 3 (CHD possible and probable, respectively). RESULTS: Re
      reading of the constructed sample for the baseline records (11 years later)
      generated 21 Summary code reassignments (2 unlikely to possible or probable; 19
      possible or probable to unlikely); re-reading for the follow-up records (0.5
      years later) generated only 8 summary code reassignments (21 vs 8p < 0.001) (3
      unlikely to possible or probable; 4 possible or probable to unlikely; 1 probable
      to possible). Re-reading increased the estimated net ECG deterioration in the
      constructed sample from 11.8 % to 25.4%. Consistency analysis showed most
      variability in marginal baseline abnormalities. CONCLUSION/INTERPRETATION: Coding
      variability is now small though re-reading suggests some time-dependent coding
      drift. Relative over-reading at baseline suggests that the change reported in the
      complete WHO MSVDD cohort at follow-up was underestimated and that almost all of
      the reported ECG deterioration and about half of the reported ECG 'improvement'
      was real.

PMID- 11587054
TI  - Vascular disease in younger-onset diabetes: comparison of European, Asian and
      American Indian cohorts of the WHO Multinational Study of Vascular Disease in
      Diabetes.
AB  - AIMS/HYPOTHESIS: This study compared the incidence of vascular disease in
      subjects with younger-onset diabetes from different ethnic groups. METHODS: The
      incidence of vascular disease endpoints has been studied in a sub-group (n = 994)
      of participants of the World Health Organization Multinational Study of Vascular
      Disease in Diabetes (WHO MSVDD) who had younger-onset diabetes (diagnosed before
      the age of 30 years). The study participants have been divided into European (n =
      631), Asian (n = 84) and American Indian (n = 91) cohorts. RESULTS: For Type I
      (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus,
      American Indian men had a higher incidence of lower-extremity amputation and
      renal failure than the other cohorts, whereas European women had a higher
      incidence of angina than other cohorts. American Indians also had a higher
      incidence of any retinopathy, clinical proteinuria and albuminuria than the
      European and Asian cohorts. CONCLUSION/INTERPRETATION: This study confirms the
      high burden of large and small-vessel disease complications manifest in American
      Indian people with younger-onset diabetes.

PMID- 11587055
TI  - Vascular disease prevalence in diabetic patients in China: standardised
      comparison with the 14 centres in the WHO Multinational Study of Vascular Disease
      in Diabetes.
AB  - AIMS/HYPOTHESIS: Rates of vascular complications of diabetes in a cohort of
      mainland Chinese patients with diabetes, ascertained and examined by similar
      methodology, are compared with those of the WHO Multinational Study of Vascular
      Disease in Diabetes (WHO MSVDD). METHODS: The standardised procedures carried out
      in the WHO MSVDD were followed in assembling and examining a Chinese cohort of
      447 diabetic patients recruited in Beijing and Tianjin [2]. RESULTS: Compared
      with the WHO MSVDD centres, the Chinese cohort was slightly older, had a shorter
      duration of known diabetes and had fewer insulin-treated patients. Arterial
      pressure, total blood cholesterol and body mass index were substantially lower.
      Large vessel disease rate for age, sex and duration adjusted data (17.9 % ) was
      about half that of the combined WHO MSVDD centres (33.5 % p < 0.001). However,
      retinopathy (47.4% vs 35.8% p < 0.001) and proteinuria (57.1 vs 24.9 % p < 0.001)
      rates were significantly higher. CONCLUSION/INTERPRETATION: Relatively low
      arterial pressures and blood cholesterol are likely contributors to the notably
      low arterial disease rates in this Chinese diabetic cohort; they reflect low
      rates in the Chinese mainland general population and resemble the Tokyo and Hong
      Kong centres of the WHO MSVDD. The high rates of retinopathy and proteinuria
      could relate to later diagnosis, degree of hyperglycaemia and/or increased
      susceptibiltiy to microangiopathy.

PMID- 11587056
TI  - Single photon emission CT and positron emission tomography in the evaluation of
      neurologic disease.
AB  - Widely available SPECT allows imaging of certain critical components of
      neurotransmission, providing clinically and experimentally significant
      information. Future efforts may be directed toward developing innovative
      techniques to delineate dynamic neurochemical changes in vivo.

PMID- 11587057
TI  - Radionuclide imaging of acute pulmonary embolism.
AB  - From the prospective and outcome-based studies that have been carried out in the
      past few years, the following conclusions regarding the diagnostic evaluation of
      patients with suspected PE can be made: 1. A normal V/Q scan interpretation
      excludes the diagnosis of clinically significant PE. 2. Patients with a very-low-
      or low-probability V/Q scan interpretation and a low clinical likelihood of PE do
      not require angiography or anticoagulation. 3. Patients with a very-low- or low
      probability V/Q scan interpretation, an intermediate or high clinical likelihood
      of PE, and negative serial noninvasive venous studies of the lower extremities do
      not require anticoagulation or angiography. If serial noninvasive venous studies
      of the lower extremities are positive, patients should be treated. 4. Clinically
      stable patients with an intermediate-probability V/Q scan interpretation require
      noninvasive venous studies of the legs and, if negative, require CT angiography
      or pulmonary angiography for a definite diagnosis. 5. Clinically stable patients
      with a high-probability V/Q scan interpretation and a high clinical likelihood of
      PE require treatment and need no further diagnostic tests to confirm the
      diagnosis. 6. Clinically stable patients with a high-probability V/Q scan
      interpretation and a low or intermediate clinical likelihood of PE require
      noninvasive venous studies of the legs and, if negative, often require CT
      angiography or pulmonary CT for a definitive diagnosis.

PMID- 11587058
TI  - The role of nuclear medicine in breast cancer detection: functional breast
      imaging.
AB  - Mammography remains the imaging modality of choice in detection of early,
      nonpalpable breast cancer. Scintimammography using SPECT, however, may prove to
      be a very useful adjunct to a nondiagnostic or difficult mammogram. Further
      prospective studies have to be designed so that the specific clinical
      applications of this technique are more defined. As with any new imaging
      procedure, special care to obtain high-quality scintimammographic studies and
      sufficient training of staff to perform and interpret the imaging are necessary.

PMID- 11587059
TI  - Positron emission tomography: brain tumors and lung cancer.
AB  - F-18 fluorodeoxyglucose positron emission tomography is a uniquely powerful
      diagnostic tool that noninvasively provides information that is critical to
      appropriate clinical management of patients with non-small cell lung cancer. Not
      only does the functional information provided by PET complement and clarify the
      anatomic information supplied by CT and MR imaging, but the superior sensitivity
      and negative predictive value of PET allow for improved accuracy in diagnosis,
      prognosis, staging, and monitoring the effects of treatment. With better
      information at their disposal, clinicians and patients are able to make better
      informed decisions, contributing to more appropriate and more cost-effective
      medical care. Truly, FDG-PET has earned its place as the new standard of care in
      imaging non-small cell lung cancer.

PMID- 11587060
TI  - Positron emission tomography imaging in oncology.
AB  - The applications for FDG-PET imaging are rapidly growing and accepted in the
      field of oncology. FDG-PET imaging does not replace other imaging modalities,
      such as CT, but seems to be very helpful in specific situations where CT has
      known limitations, such as differentiation of benign from malignant indeterminate
      lesions on CT, differentiation of post-treatment changes versus recurrent tumor,
      differentiation of benign from malignant lymph nodes, and monitoring therapy. The
      biggest use of FDG-PET presently is in N and M staging of various body tumors.
      The addition of FDG-PET in the evaluation of oncologic patients in well-defined
      algorithms including a combination of imaging studies seems to be cost effective
      by accurately identifying patients who benefit from invasive procedures and
      saving unnecessary costly invasive procedures on patients who do not benefit from
      them. Although PET imaging may decrease the cost of health care by reducing the
      number of invasive procedures, implementation of clinical PET has been hindered
      by the high cost of the purchase, operation expenses, and maintenance of PET
      systems; the need for immediate access to a source of 18F (owing to the 110
      minute half-life); and the limited reimbursement for clinical procedures by third
      party payers. These combined factors have resulted in the development by
      manufacturers of hybrid gamma camera systems capable of performing positron
      imaging. These systems can be used to image conventional radiopharmaceuticals
      used in general nuclear medicine and positron-emitting radiopharmaceuticals. The
      performance of these camera-based PET systems has improved markedly over the past
      few years with the introduction of thicker NaI (T1) crystals, iterative
      reconstruction algorithms, and attenuation correction. These new developments in
      medical imaging instrumentation have contributed to the expansion of the number
      of cyclotrons, and have driven the concept of commercial FDG distribution
      centers.

PMID- 11587061
TI  - Positron emission tomography instrumentation.
AB  - Positron emission tomography scanning has evolved over the past 40 years from a
      tool used predominantly for research to a valued clinical imaging modality.
      Current PET scanners must perform high-quality whole-body PET and brain PET.
      There are several levels of PET devices from the dedicated, high-end scanners
      down to the hybrid PET-SPECT systems offering varying levels of performance. The
      next generation of PET scanners will most likely involve the use of new
      scintillating materials. There is also a growing interest in dedicated devices
      for specific applications, such as high-resolution scanners for imaging small
      animals.

PMID- 11587062
TI  - Nuclear cardiology update.
AB  - This article focuses on the following areas of myocardial perfusion imaging:
      radiotracer and protocol options, pharmacologic stress agents, and protocols and
      functional assessment with ECG-gated single photon emission CT.

PMID- 11587063
TI  - Sentinel node staging of early breast cancer using lymphoscintigraphy and the
      intraoperative gamma detecting probe.
AB  - Lymphoscintigraphy combined with intraoperative gamma-probe detection of sentinel
      lymph nodes in patients with inoperable early primary breast cancers is effective
      for staging the disease. The clinical alternative is axillary lymph node
      dissection, which is a far more invasive procedure and is accompanied by
      significant morbidity. Accuracy of staging is enhanced by immunohistochemical
      staining of micrometastases, which pathologists can easily perform for one to
      three sentinel lymph nodes, but not for 20 to 30 nodes, using axillary dissection
      procedure. Optimum methodology is presented for performing sentinel lymph node
      imaging and is important for accurate identification of sentinel node(s).

PMID- 11587064
TI  - Radionuclide evaluation of patients with lymphoma.
AB  - Nuclear medicine imaging techniques allow us to peer into physiologic processes,
      avoiding the need to wait until anatomic changes are detectable, and allowing for
      prompt, informed management decisions. Recognition of normal, abnormal, and post
      therapy scan patterns is critical to achieve the necessary sensitivity and
      specificity needed for patient management. Gallium scintigraphy using updated
      techniques has an important continuing role in management of patients with
      lymphoma. Gallium scintigraphy can contribute to patient management primarily by
      detecting residual disease or relapse after treatment, monitoring response during
      therapy, and providing prognostic information. FDG and PET cameras, especially
      dedicated ring systems, offer high resolution and high-contrast images, thereby
      demonstrating additional sites of disease. Although preliminary evidence looks
      promising that FDG can provide all information that Ga-67 has been shown to do in
      the past, additional data are required. Further studies will show whether FDG-PET
      can provide prognostic information and predict disease-free and overall survival,
      the availability of both FDG and PET scanners, and issues of cost. Patient
      accessibility will undoubtedly also play a role in when, or whether, FDG-PET will
      totally replace Ga-67 scintigraphy in the management of patients with lymphoma.

PMID- 11587065
TI  - Diuretic renography and angiotensin converting enzyme inhibitor renography.
AB  - Renovascular hypertension and renal outlet obstruction are two clinical
      conditions well evaluated by nuclear medicine techniques. They both require a
      specific intervention to challenge a specific aspect of renal functional reserve.
      Diuretic renography is the oldest common example in nuclear medicine where
      functional change in the kidney is provoked for diagnostic purposes. The kidney's
      tubular functional reserve, in this instance, is challenged to induce diuresis
      and increase urine flow. This intervention permits diuretic renography to retain
      an essential role in the evaluation of hydroureteronephrosis. Captopril
      renography is a more recent example of a similar principle and depends on a
      reactive renin-angiotensin system to identify a kidney responsible for RVH. In
      both renal outlet obstruction and RVH, an anatomic abnormality is also identified
      (hydronephrosis and RAS, respectively) at some point in the diagnostic workup.
      The final diagnosis in each instance, however, depends on evidence for a
      functional disorder, provoked and measured during the radionuclide interventional
      examination. These serve as excellent examples of the power of functional imaging
      to identify specific medical disorders.

PMID- 11587066
TI  - Cholecystokinin cholescintigraphy: clinical indications and proper methodology.
AB  - Cholecystokinin is a useful diagnostic adjunct to cholescintigraphy. Clinical
      indications include contracting the gallbladder before cholescintigraphy in
      patients fasting greater than 24 hours, during cholescintigraphy to diagnose
      sphincter of Oddi dysfunction, and after cholescintigraphy to exclude acute
      acalculous cholecystitis, differentiate common duct obstruction from normal
      variation, and to confirm the diagnosis of chronic acalculous cholecystitis.
      Proper methodology is mandatory for a diagnostically useful test. Data presented
      shows that a 3-minute infusion of 0.01 or 0.02 microg/kg is nonphysiologic and
      often results in ineffective contraction similar to that seen with a bolus
      infusion. Normal gallbladder ejection (GBEF) values cannot be established using a
      3-minute infusion because of the wide variability in response. Instead, infusions
      of 30 or 60 minutes are required. Normal GBEF values have been established for
      these methods and are 30% and 40%, respectively.

PMID- 11587067
TI  - Linkage disequilibrium and haplotype analysis among four novel single-nucleotide
      polymorphisms in the human leukemia inhibitory factor (LIF) gene.
AB  - Leukemia inhibitory factor (LIF) is a pleiotropic cytokine implicated in various
      pathological conditions, such as rheumatoid arthritis and osteoporosis. Despite
      the possible importance of LIF as a therapeutic target, little is known about the
      bioregulation of the human LIF gene. We here sequenced the entire structure of
      the LIF gene of 48 alleles in the Japanese population. These experiments
      identified four single-nucleotide polymorphisms (SNPs) and determined their
      allelic frequencies from a 48-allele sequence in the Japanese population. All
      four SNPs found in the LIFgene were located within exon 3, that is, a C/T at
      nucleotide (nt) position 3951, a C/G at nt position 4376, an A/C at nt position
      4442, and a G/A at nt position 5961 (nucleotide numbering starts from the ATG
      start codon). Based on the genotypic data, we constructed four major haplotypes
      in the tested population. Two-way comparisons of SNPs revealed complete linkage
      disequilibrium between SNPs at positions 3951, 4376, and 4442. These results may
      prove to be useful as genetic markers for population-based disease-association
      studies in osteoporosis.

PMID- 11587068
TI  - Eight novel mutations of the androgen receptor gene in patients with androgen
      insensitivity syndrome.
AB  - Androgen insensitivity syndrome (AIS) is an X-linked genetic disorder of male
      sexual differentiation caused by mutations in the androgen receptor (AR) gene. A
      reliable genotype-phenotype correlation in these patients does not exist as yet.
      Here we report the molecular studies performed on eight individuals with AIS.
      Exon-specific polymerase chain reaction (PCR), single-strand conformation
      polymorphism, and sequencing analyses, were performed in exons 2 to 8 of the AR
      gene. In one case, total cellular RNA was extracted from genital skin fibroblasts
      and reverse transcriptase-PCR was performed. Six different point mutations
      leading to amino acid substitutions (P682T, Q711E, G743E, F827V, H874R, D879Y),
      one splice-junction mutation (g-->c at +5, exon 6/intron 6), and a missense
      mutation without amino acid substitution (S888S) were identified. All mutations,
      including a de novo mutation, were previously undescribed on the steroid binding
      domain. Of the eight mutations identified, four led to a complete female
      phenotype (codons 743, 827, 874 and the donor splice site +5), two were detected
      in phenotypic females with partial virilization (codons 682 and 711), and two
      were present in phenotypic male subjects with undervirilized external genitalia,
      thus indicating that all of these sites determine AR functional activity.

PMID- 11587069
TI  - Identification of GFAT1-L, a novel splice variant of human glutamine: fructose-6
      phosphate amidotransferase (GFAT1) that is expressed abundantly in skeletal
      muscle.
AB  - Glutamine:fructose-6-phosphate amidotransferase (GFAT1) is the rate-limiting
      enzyme in the hexosamine biosynthetic pathway, which plays an important role in
      hyperglycemia-induced insulin resistance. To evaluate the role of GFAT1
      expression, we analyzed the expression profiles of GFAT1 mRNA in various human
      tissues using reverse transcriptase-polymerase chain reaction. We report here the
      identification and cDNA cloning of a novel GFAT1 splice variant expressed
      abundantly in skeletal muscle and heart. This subtype, designated GFAT1-L,
      contains a 54-bp insertion within the GFAT1 coding sequence. Recombinant GFAT1-L
      protein possessed functional GFAT activities and biochemical characteristics
      similar to GFAT1. Previously, GFAT1 was considered a simplex enzyme. The
      identification of a novel GFAT1 subtype possessing functional enzymatic activity
      and tissue-specific expression should provide additional insight into the
      mechanism of skeletal muscle insulin resistance and diabetes complications.

PMID- 11587070
TI  - Characterization of genomic rearrangements of the alpha1-acid
      glycoprotein/orosomucoid gene in Ghanaians.
AB  - In this study, the structure of the alpha1-acid glycoprotein (AGP), or
      orosomucoid (ORM), gene was investigated in a Ghanaian mother and her child, who
      shared an unusual variant, ORM1 S2(C), found by isoelectric focusing. Three
      remarkable changes of nucleotide sequence were observed: (1) The two ORM1
      alleles, ORMI*S and ORMI*S2(C), had the AGP2 gene-specific sequence at one and
      three regions, respectively, in exon 5 to intron 5. The variant allele
      originating from ORMi*S was characterized by a G-to-A transition, resulting in an
      amino acid change from valine to methionine, which is also detected in ORM1 F2, a
      form that is common in Europeans. (2) The AGP2 gene of the child, inherited from
      the father, was duplicated, as revealed by long-range polymerase chain reaction.
      (3) Three new mutations were observed in two exons of the AGP2 genes of the
      mother and child. All of these novel genomic rearrangements, which were not
      observed in Japanese subjects, may have arisen through point mutation, gene
      conversion, and unequal crossover events. It is likely that the rearrangement of
      the AGP gene has often occurred in Africans.

PMID- 11587071
TI  - Diagnosis of Alexander disease in a Japanese patient by molecular genetic
      analysis.
AB  - Alexander disease is a leukodystrophy that is neuropathologically characterized
      by the presence of numerous Rosenthal fibers in astrocytes. Recently, mutations
      in the gene encoding glial fibrillary acidic protein (GFAP) were identified in
      patients with Alexander disease. We sequenced the GFAP gene of a Japanese girl
      who presented with typical symptoms of Alexander disease but in whom the
      diagnosis was not proven by histopathology. We identified a missense mutation,
      R239C, which is identical to the mutation previously reported to be most
      frequent. As was the case in previously described patients, our patient was also
      heterozygous for the de novo mutation. Interestingly, despite the fact that this
      is a de novo mutation, R239C was found to be common in different ethnic groups,
      implying that the site is a "hot spot" for mutagenesis. Molecular genetic
      analysis now makes the antemortem diagnosis of Alexander disease possible.

PMID- 11587072
TI  - The DIRC1 gene at chromosome 2q33 spans a familial RCC-associated t(2;3)(q33;q21)
      chromosome translocation.
AB  - A reciprocal, balanced, constitutional chromosome translocation, t(2;3)(q33;q21),
      which is associated with familial clear cell renal cancer, has been described and
      the genomic regions surrounding the 2q and 3q breakpoints have been
      characterized. Based on the genomic map of the 2q break, EST AI468595 was
      positioned near the 2q33 translocation and the full-length gene and cDNA were
      isolated. This 57-kb gene, designated the DIRC1 gene, was disrupted between exons
      1 and 2 by the familial translocation. The 1.5-kb mRNA encodes an 11-kDa
      predicted protein of 104 amino acids. Low-level expression of DIRC1 was detected
      by reverse transcriptase-polymerase chain reaction amplification in adult
      placenta, testis, ovary, and prostate and in fetal kidney, spleen, and skeletal
      muscle. A GFP-Dirc1 fusion protein was expressed in vitro and a polyclonal anti
      Dircl peptide serum was prepared. A panel of cancer and cancer-derived cell line
      DNAs was examined for DIRC1 mutations, but only a rare polymorphism was observed.
      Two familial tumors showed loss of the derivative 3 chromosome, as observed in a
      Dutch kindred with t(2;3)associated renal cancers. Mutations in the second DIRC1
      allele were not detected. Further studies will be required to determine if
      disruption of the DIRC1 gene contributed to development of the associated
      familial clear cell renal cancers.

PMID- 11587073
TI  - Catalog of 46 single-nucleotide polymorphisms (SNPs) in the microsomal
      glutathione S-transferase 1 (MGST1) gene.
AB  - A major goal in our laboratory is to understand the role of common genetic
      variations among individual patients as regards susceptibility to common diseases
      and differences in therapeutic efficacy and/or side effects of drugs. As an
      addition to the high-density SNP (single-nucleotide polymorphism) maps of 12
      glutathione S-transferase and related genes reported earlier, we provide here an
      SNP map of the microsomal glutathione S-transferase 1 (MGST1) gene. Among 48
      healthy Japanese volunteers examined. we identified a total of 46 SNPs at this
      locus, 36 of which had not been reported before: 4 in the promoter region, 34 in
      introns, 3 in the 3' untranslated region, and 5 in the 3' flanking region. No SNP
      was found in 5'untranslated or coding regions. The ratio of transition to
      transversion was approximately 1.2:1. Among the 13 insertion-deletion
      polymorphisms was a 2-bp deletion in the coding region of MGST1 in DNA from one
      of the volunteers, which resulted in a frame-shift mutation. Since the gene
      product encoded by this mutant allele would lack the C-terminal half including
      the MAPEG (membrane-associated proteins in eicosanoid and glutathione metabolism)
      domain, MGST1 activity is likely to be reduced in the carrier's cells. The SNP
      map presented here adds to the archive of tools for studying complex genetic
      diseases, population migration patterns, and a variety of pharmacogenetic
      possibilities.

PMID- 11587074
TI  - Frequency and clinical features of patients with sensorineural hearing loss
      associated with the A3243G mutation of the mitochondrial DNA in otorhinolaryngic
      clinics.
AB  - The A3243G mutation of the mitochondrial gene is a cause of maternally inherited
      diabetes and deafness. The aim of this study was to evaluate the frequency and
      clinical features of this mutation in patients with sensorineural hearing loss
      (SNHL) in otorhinolaryngic clinics. The frequency of the A3243G mutation in 230
      patients with SNHL was 1.74% (4/230). Three of the four patients had diabetes
      mellitus (DM) and were already aware that they had the mutation. The other had
      cardiomyopathy but not DM, and proved to have the mutation in this study. The
      frequency of the mutation was 12.9% (4/31) in patients with a family history of
      possible maternal inheritance of SNHL, 10.3% (3/29) in patients with DM, and 50%
      (3/6) in patients with both. The age of onset of SNHL in these patients and their
      families was between their teens and their forties. The chance of diagnosing the
      A3243G mutation in patients with SNHL in otorhinolaryngic clinics is probably
      less than 1%. Association of DM, cardiomyopathy, a family history of possible
      maternal inheritance of SNHL, and an onset of SNHL between the teens and the
      forties are signs suggesting the mutation. These signs provide us with a reason
      for genetic testing for the mutation.

PMID- 11587075
TI  - Germline transmission of a transferred human chromosome 21 fragment in
      transchromosomal mice.
AB  - We generated transchromosomal (Tc) mice containing a human chromosome 21 fragment
      (hCF21) using mouse embryonic stem (ES) cells with the transferred hCF21. Here we
      report breeding analyses that test the maintenance rate of the hCF21 in Tc mice
      of two different genetic backgrounds, MCH (ICR) and C57BL/6. Fluorescence in situ
      hybridization and polymerase chain reaction-based DNA analyses revealed that the
      structure of the hCF21 fragment including the CBR1, SIM2, HLCS, and D21S268
      markers, was approximately 5 Mb in size, and was transmitted at least to the F3
      generation. Though the retention rate of the hCF21 was variable among individual
      mice, for example, 21%-92% in brain and 10%-92% in tail fibroblasts, the C57BL/6
      background yielded a higher retention rate than did the MCH (ICR). These results
      suggest that the hCF21 could be maintained stably in Tc mice, depending on the
      genetic background. The panel of Tc mice will be a useful model to investigate
      the function of genes on the hCF21 fragment in various tissues through germinal
      transmission.

PMID- 11587076
TI  - A method for the quantitative evaluation of SAR distribution in deep regional
      hyperthermia.
AB  - The Specific Absorption Rate (SAR) distribution pattern visualization by a matrix
      of E-field light-emitting sensors has demonstrated to be a useful tool to
      evaluate the characteristics of the applicators used in deep regional
      hyperthermia and to perform a quality assurance programme. A method to quantify
      the SAR from photographs of the sensor array--the so-called 'Power Stepping
      Technique'--has already been proposed. This paper presents a new approach to the
      quantitative determination of the SAR profiles in a liquid phantom exposed to
      electromagnetic fields from the Sigma-60 applicator (BSD-2000 system for deep
      regional hyperthermia). The method is based on the construction of a 'calibration
      curve' modelling the light-output of an E-field sensor as a function of the
      supplied voltage and on the use of a reference light source to 'normalize' the
      light-output readings from the photos of the sensor array, in order to minimize
      the errors introduced by the non-uniformity of the photographic process. Once the
      calibration curve is obtained, it is possible, with only one photo, to obtain the
      quantitative SAR distribution in the operating conditions. For this reason, this
      method is suitable for equipment characterization and also for the control of the
      repeatability of power deposition in time.

PMID- 11587077
TI  - Variations of focal regions versus numbers and positions of sources in two
      dimensional media.
AB  - This paper explores the behaviour of the primary and secondary hot spots in
      homogeneous and two-dimensional inhomogeneous medium. Circular arrays are
      considered with a radius of up to five wavelengths. The number of sources and
      their positions in the array are varied, and the influence of these variations on
      the primary and secondary hot spots is observed. It is found that the primary hot
      spot reaches its final shape with the addition of a very small number of sources
      to the array. An increase in the number of sources results in a reduction of the
      normalized magnitude of the secondary hot spots, but the size of the normalized
      primary hot spot remains the same. An upper limit of sources in the array exists
      after which no further reduction of the secondary hot spots is observed. The
      finite-difference time-domain method (FDTD) is used to obtain the electric-field
      distribution in the inhomogeneous medium. A genetic algorithm is then applied to
      find the optimal positions of the antennae in the array.

PMID- 11587078
TI  - Cyclooxygenase inhibitors are potent sensitizers of prostate tumours to
      hyperthermia and radiation.
AB  - It has previously been demonstrated that hyperthermia can activate prostaglandin
      synthesis and that prostaglandins are protective against hyperthermia. This study
      examined the use of inhibitors of prostaglandin synthesis on the response of
      prostate tumours to hyperthermia. The non-steroidal anti-inflammatory drugs
      (NSAID) ibuprofen and sulindac, known cyclooxygenase inhibitors that inhibit
      prostaglandin production, were effective hyperthermia sensitizers and augmented
      growth delay of DU-145 and PC-3 prostate tumours to combined radiation and
      hyperthermia treatment protocols. Pre-treatment of mice with ibuprofen and
      sulindac at hyperthermia sensitizing doses resulted in significant (p < 0.01)
      inhibition of hyperthemia-induced serum prostaglandin E2. These findings indicate
      that NSAID may have both sensitizing effects on prostate tumour growth and may
      function by inhibiting prostaglandin synthesis.

PMID- 11587079
TI  - Heat-induced p53-dependent signal transduction and its role in hyperthermic
      cancer therapy.
AB  - A tumour suppressor gene product, p53, is well known to be activated by genotoxic
      stress such as radiation and DNA damaging agents. Recently, it has been found
      that non-genotoxic physiological stresses such as heat, cold and low pH also
      activate p53, which regulates the expression of downstream genes. p53 was found
      to contribute to heat sensitivity through Bax-mediated apoptosis via activation
      of caspase-3 in the human cancer cells. This study reviews heat-induced p53
      dependent signal transduction and heat sensitivity via a p53-regulated pathway
      for apoptosis in human cancer cells with identical genetic backgrounds except for
      p53 status. Furthermore, based on recent reports, it is proposed that p53 status
      could be a useful indicator in predictive assays for hyperthermic cancer therapy.
      Hyperthermia treatment based on such predictive assays might improve the outcome
      and efficiency of cancer therapy in the future. It is further proposed that
      manipulation of mp53 by glycerol as a chemical chaperone may provide a new cancer
      therapy for patients with mp53-tumours.

PMID- 11587080
TI  - Effect of whole body hyperthermia on radiation therapy of transplanted
      fibrosarcoma in Swiss mice.
AB  - The exposure of normal mice to whole body hyperthermia (1 h WBH at 39 or 40
      degrees C), 20 or 48 h prior to total body irradiation (TBI) with lethal doses of
      gamma-rays affords significant protection as assessed by survival. The
      radioprotective effect of WBH, as observed in normal mice, diminished in tumour
      bearing mice depending upon the size of tumour. Treatment of tumour bearing mice
      with mild WBH, 20 h prior to local irrradiation (LIR), did not protect the
      transplanted tumour against radiotherapy with a single dose of 20 Gy or
      fractionated dose (in five fractions) of 7.5 Gy on alternate days. In fact, mild
      WBH treatment enhanced the tumour regression and increased the mean survival time
      after fractionated dose therapy. However, the prior mild WBH was found to be
      ineffective in protecting normal tissue, as assessed by skin contraction after
      local irradiation (50 Gy). This indicates that mild WBH treatment given 20 h
      prior to local radiotherapy enhances fibrosarcoma tumour regression but cannot
      protect skin (normal tissue) against local irradiation. It appears that
      radioprotection of animals by WBH may be the consequence of its radioprotective
      effect on haemopoietic tissues mediated through certain cytokines. Perhaps WBH
      may not have a radioprotective effect on other tissues, as evident from skin
      contraction studies.

PMID- 11587081
TI  - Whole body hyperthermia and preconditioning of the heart: basic concepts,
      complexity, and potential mechanisms.
AB  - Whole body hyperthermia (WBH) is a distinctive pathophysiological condition with
      significant impact on tissue metabolism and organ functions. WBH has been
      investigated as a promising adjunct therapy to the conventional chemo- or
      radiotherapy for treating certain types of cancer. Numerous studies have shown
      that WBH is associated with induction of heat shock proteins (HSPs), which in
      turn modulate cellular survival or death. A brief period of WBH (40-42 degrees C;
      15-20 min) can induce delayed protection against lethal endotoxemia as well as
      various forms of injury in brain, heart, liver, lungs, small intestine, and
      skeletal muscle. This review article focuses on discussing the WBH-induced
      myocardial protection against ischemia/reperfusion injury. Most recently,
      possible involvement of protein kinase C, mitogen-activated protein kinases,
      nitric oxide, ATP-sensitive potassium channels, and neural peptides in the signal
      transduction pathways has been demonstrated. On the other hand, whether HSPs or
      antioxidant enzymes are the primary end-effector of the cardioprotection
      continues to be a matter of ongoing debates. It has also been recognized that the
      complex nature of WBH may be the responsible factor for the discordant results
      among various studies, especially across different animal species or strains, in
      terms of the time course and potency of WBH-induced cardioprotection.
      Nevertheless, a better understanding of the WBH-elicited myocardial ischemic
      resistance may have a wide spectrum of clinical implications as well as
      insightful inputs into the hyperthermic biology.

PMID- 11587082
TI  - Chemohyperthermia for advanced abdominal malignancies: a new procedure with
      closed abdomen and previously performed anastomosis.
AB  - ChemoHyperthermic Peritoneal Perfusion (CHPP) after cytoreductive surgery is a
      relatively new procedure in the treatment of abdominal carcinomatosis or
      sarcomatosis. An assessment of the CHPP technique performed on 20 patients
      suffering from abdominal malignancies was carried out. After surgical debulking
      and gastrointestinal anastomosis, two Tenckhoff catheters were positioned for the
      immediate performance of CHPP, which was carried out at 42-43 degrees C for 1 h,
      after closing the abdomen. In 19 assessable patients, 47.3% and 36.8% complete
      responses (CR) were recorded at 1 and 6 months, respectively, with responses of
      37.5% in patients affected with gastrointestinal cancer and 50% in patients
      affected with ovarian cancer. CR were obtained only in patients who had undergone
      accurate peritoneal debulking. Survival rate for gastrointestinal and ovarian
      cancer was 68% at 12 months. Patients who underwent radical cytoreductive surgery
      are all alive at a follow-up median time of 17 months. Two anastomotic leakages
      with spontaneous recovery were observed, along with one hydrothorax, which was
      immediately drained during the procedure, three cases of chemotherapic
      gastrointestinal toxicity, one sepsis, one renal failure that required a
      transient dialysis, and one cholecystitis that required cholecystectomy. One
      patient died 30 days after CHPP of a cardiac ischaemia not strictly related to
      the surgical procedure. In the authors' experience, CHPP with closed abdomen
      after reconstructive gastrointestinal surgery is a safe and feasible treatment
      with acceptable side effects.

PMID- 11587083
TI  - Cellular communication and coupling within the suprachiasmatic nucleus.
AB  - In mammals, the part of the nervous system responsible for most circadian
      behavior can be localized to a pair of structures in the hypothalamus known as
      the suprachiasmatic nucleus (SCN). Importantly, when SCN neurons are removed from
      the organism and maintained in a brain slice preparation, they continue to
      generate 24h rhythms in electrical activity, secretion, and gene expression.
      Previous studies suggest that the basic mechanism responsible for the generation
      of these rhythms is intrinsic to individual cells in the SCN. If we assume that
      individual cells in the SCN are competent circadian oscillators, it is obviously
      important to understand how these cells communicate and remain synchronized with
      each other. Cell-to-cell communication is clearly necessary for conveying inputs
      to and outputs from the SCN and may be involved in ensuring the high precision of
      the observed rhythm. In addition, there is a growing body of evidence that a
      number of systems-level phenomena could be dependent on the cellular
      communication between circadian pacemaker neurons. It is not yet known how this
      cellular synchronization occurs, but it is likely that more than one of the
      already proposed mechanisms is utilized. The purpose of this review is to
      summarize briefly the possible mechanisms by which the oscillatory cells in the
      SCN communicate with each other.

PMID- 11587084
TI  - Does the difference in the timing of eclosion of the fruit fly Drosophila
      melanogaster reflect differences in the circadian organization?
AB  - The eclosion rhythm of a laboratory population of Drosophila melanogaster was
      studied under 12h light, 12h dark (LD 12:12) cycles. Although most of the flies
      were found to eclose just after "lights on" in LD 12:12, termed within gate (WG)
      flies, a few flies were found to eclose nearly 10h after peak eclosion, termed
      outside gate (OG) flies. The circadian parameters of the clocks controlling
      oviposition rhythms in the WG and the OG flies were estimated to understand the
      cause of such differences in the timing of eclosion. The distribution of the
      fraction of individual flies exhibiting single, multiple, and no significant
      period in the WG flies was significantly different from distribution in the OG
      flies. Compared to the WG flies, more OG flies were found to exhibit oviposition
      rhythm with multiple periodicity, whereas more WG flies exhibited an oviposition
      rhythm with a single significant period. The fraction of flies with arrhythmic
      oviposition was similar in both the WG and the OG flies. Free-running period tau
      in constant darkness (DD) and the phase angle difference psi in LD 12:12 for the
      oviposition rhythm of WG and OG flies were significantly different. These results
      suggest that the differences in the time of eclosion between the flies eclosing
      within the gate and outside the gate of eclosion are probably due to differences
      in the circadian system controlling eclosion, which is reflected by the
      differences in their oviposition rhythm.

PMID- 11587085
TI  - Further characterization of the phenotype of mCry1/mCry2-deficient mice.
AB  - Mice lacking cryptochromes (mCry1/mCry2-/-) were kept in a 16h light, 8h dark,
      light-dark (16:8 LD) cycle and were given additional pulses of light of different
      brightness, starting 2h after dark onset and lasting for 1h. The suppression of
      wheel running during these light pulses (i.e., masking) was compared to that of
      wild types. No evidence of any decrement in the masking response to light was
      detected. As well as studying masking, minor bouts of activity occurring in the
      main light portion of a light-dark cycle were quantified. One possible
      explanation of such predark activity is that some damped endogenous process is
      spared in mCry1/mCry2 double-knockout mice.

PMID- 11587086
TI  - Circadian pacemaker function and entrainment during maturation of transgenic
      hypertensive TGR(mREN2)27 and Sprague-Dawley rats.
AB  - TGR(mREN2)27 (TGR) transgenic rats develop hypertension due to the mouse mRen-2
      gene inserted in their genome. At 5 weeks of age, the blood pressure of TGR rats
      starts rising, until a maximum is reached at 10 weeks of age. Adult TGR rats show
      peak values of blood pressure (BP) during the light phase, while heart rate (HR)
      and motor activity (MA) peak at night. In the present experiment, we evaluated
      the evolution of circadian rhythms in motor activity, heart rate, and blood
      pressure of TGR and Sprague-Dawley (SD) rats under 12h light-dark cycles (LD
      12:12). Results confirmed that the blood pressure of TGR rats starts to increase
      at 5 weeks of age, reaching a plateau by the 11th week. Parallel to the increase
      in blood pressure levels, there was a decrease in the period length of the blood
      pressure rhythm, a delay in the onset of the alpha phase of the blood pressure
      rhythm with respect to that of motor activity and heart rate, and a decrease in
      heart rate levels. In all of the variables studied, the alpha phase of SD rats
      always started before darkness, whereas that of TGR rats started after lights
      off. In general, heart rate and motor activity levels of TGR rats were higher
      than those of SD rats. The amplitude of the circadian rhythms studied was greater
      in TGR rats than in SD rats. The present results suggest that the different
      evolution of circadian rhythms in TGR and SD rats might be due to differences in
      the functioning of the entrainment pathway or the circadian clock itself, which
      can be detected in young rats and that are probably caused by the expression of
      the mouse transgene.

PMID- 11587087
TI  - Effect of short light-dark cycles on young and adult TGR(mREN2)27 rats.
AB  - Animals placed under short light-dark (LD) cycles show a dissociation of their
      circadian rhythms. However, this effect has only been studied in Wistar rats and
      with the motor activity (MA) rhythm. Thus, in the present experiment, we studied
      in TGR(mREN2)27 (TGR) rats, a strain of hypertensive rats, the effect of a short
      LD cycle on the circadian rhythms of MA, heart rate (HR), and blood pressure
      (BP). Our aim was (1) to investigate whether the exposure of TGR rats to a short
      LD cycle induced a dissociation of their circadian rhythms, (2) to study the
      effect of short LD cycles on the development of the circadian rhythms of TGR
      rats, and (3) to compare the effect of short LD cycles on young and adult TGR
      rats. One group of TGR rats was maintained under LD cycles of 22h periods (group
      G22). The progress in time of their rhythms was compared to that of TGR rats of
      the same age that had been kept under LD cycles of 24h periods (group G24). For
      the third point, the rhythms of a group of 5-week-old TGR rats kept under LD 22h
      cycles (young rats) were compared to those of a group of 11-week-old TGR rats
      (adult rats). Results showed that there is a dissociation of the circadian
      rhythms of all the variables monitored in TGR rats maintained under LD 22h
      cycles, independent of age. We have also found that group G22 showed a higher
      increase in BP with age and a higher mortality due to malignant hypertension
      compared to group G24. Finally, it seems that it is harder for young rats to
      entrain to short LD cycles than for adult rats, and young rats have a higher
      mortality due to malignant hypertension than adult rats. In conclusion, we
      demonstrated that short LD cycles produce a dissociation in the HR, BP, and MA
      circadian rhythms. The results of this experiment, compared to those previously
      obtained in Wistar rats, suggest that the light perception, the responses of the
      circadian system to light, or both are altered in the TGR rats.

PMID- 11587088
TI  - Temporal organization of feeding in Syrian hamsters with a genetically altered
      circadian period.
AB  - The variation in spontaneous meal patterning was studied in three genotypes (tau
      +/+, tau +/- and tau -/-) of the Syrian hamster with an altered circadian period.
      Feeding activity was monitored continuously in 13 individuals from each genotype
      in constant dim light conditions. All three genotypes had on average six feeding
      episodes during the circadian cycle (about 20h in homozygous tau mutants and 22h
      in heterozygotes compared with 24h in wild-type hamsters). Thus, homozygous tau
      mutant hamsters had significantly more feeding episodes per 24h than wild types,
      and heterozygotes were intermediate. The average duration of feeding bouts (FBs)
      was indistinguishable (around 30 minutes) among the three genotypes, whereas the
      intermeal (IM) intervals were significantly shorter for homozygote tau mutant
      hamsters (99 minutes), intermediate for heterozygotes (116 minutes), and the
      longest for wild-type hamsters (148 minutes). Thus, the meal-to-meal duration was
      on average 25% shorter in homozygous tau mutants (16% in heterozygous) than in
      wild-type hamsters. The reduction of the circadian period has a pronounced effect
      on short-term feeding rhythms and meal frequency in hamsters carrying the tau
      mutation.

PMID- 11587090
TI  - Effect of light on the development of the circadian rhythm of motor activity in
      the mouse.
AB  - In previous experiments, we found that rats raised in constant light (LL)
      manifested a more robust circadian rhythm of motor activity in LL and showed
      longer phase shifts after a light pulse in constant darkness (DD) than chose
      raised under constant darkness. In addition, we observed that the effects
      produced by constant light differed depending on the time of postnatal
      development in which it was given. These results suggest that both sensitivity to
      light and the functioning of the circadian pacemaker of the rat could be affected
      by the environmental conditions experienced during postembryonic development.
      Thus, the present experiment aimed to study whether postnatal exposure to light
      could also affect the circadian system of the mouse. Three groups of mice were
      formed: One group was raised under constant darkness during lactation (DD group),
      the second under constant light (LL group), and the third under light-dark cycles
      (LD group). After lactation, the three groups were submitted first to constant
      light of high intensity, then to LD cycles, and finally to constant darkness. In
      the DD stage, a light pulse was given. Finally, mice were submitted to constant
      light of low intensity. We observed that the circadian rhythm of the DD group was
      more disturbed under constant light than the rhythm of the LL group, and that,
      when light intensity increased, the period of the rhythm of the DD group
      lengthened more than that of the LL group. No significant differences among the
      groups were found in the phase shift induced by the light pulse. Therefore, it
      appears that DD mice are more sensitive to light than their LL counterparts.
      However, at present there is no evidence to affirm that the light environment
      experienced by the mouse during postnatal development affects the circadian
      pacemaker.

PMID- 11587089
TI  - Day-night variation in the in vitro contractility of aorta and mesenteric and
      renal arteries in transgenic hypertensive rats.
AB  - TGR(mREN2)27 (TGR) rats develop severe hypertension and an inverted circadian
      blood pressure profile with peak blood pressure in the day-time rest phase. The
      present study investigated the in vitro responsiveness of different arteries of
      TGR rats during day and night. Twelve-week-old TGR rats and normotensive Sprague
      Dawley (SPRD) controls, synchronized to 12h light, 12h dark (LD 12:12) (light
      07:00-19:00), were killed at 09:00 (during rest) and 21:00 (during activity), and
      endothelium-dependent relaxation by acetylcholine and vascular contraction by
      angiotensin II were studied by measuring isometric force in ring segments of
      abdominal aorta and mesenteric and renal arteries. In SPRD rats, consistent day
      night variation was found, with greater responses to angiotensin II during the
      daytime rest span. In TGR rats, biological time-dependent differences were found
      in the renal vasculature, but not in the aorta and mesenteric artery. Relaxation
      of SPRD rat aorta and mesenteric artery by acetylcholine was greater at 09:00,
      whereas in TGR rats, day-night variation was absent (mesenteric artery) or
      inverted (aorta). In conclusion, based on the study of two time points, day-night
      variation in vascular contractility of aorta and mesenteric artery is blunted in
      TGR rats, whereas renal artery segments showed an unchanged day-night pattern
      compared to SPRD controls.

PMID- 11587091
TI  - Ultradian and circadian activity-rest rhythms of preterm neonates compared to
      full-term neonates using actigraphic monitoring.
AB  - During the first weeks of life, preterm neonates show fewer circadian rhythms in
      their physiological parameters than full-term neonates. To determine whether
      preterm neonates differ in their temporal adaptation to the day-night cycle from
      full-term neonates at the early age of 1 week, we compared activity-rest behavior
      of both groups. Activity-rest behavior of 10 neurologically healthy preterm
      neonates (born in 34th to 36th week of gestation) and 10 neurologically healthy
      full-term neonates (born in 37th to 42nd week of gestation) was monitored
      longitudinally for 8 successive days in the first 2 weeks of life. Actigraphy was
      used to register and display time patterns of activity and rest in neonates by
      using small actometers, which resemble a wristwatch. Nursing/feeding was recorded
      using the actometer's integrated event marker button. Recordings for preterm
      neonates were conducted in the hospital, recordings for full-term neonates were
      carried out in the hospital and in their homes. In addition to the actigraphic
      recordings, a standardized diary was kept regularly. To assess periodic
      characteristics, frequency components of activity-rest behavior were analyzed
      using fast Fourier transformation (FFT). Amounts of daily sleep time, nightly
      sleep time, and sleep time during 24h were compared. Nursing/feeding epochs were
      also analyzed for 5 preterm and 5 full-term neonates to compare their food intake
      behavior. The majority of preterm neonates showed a multitude of ultradian
      frequencies in their spectra. In contrast, several full-term neonates showed a
      distinct circadian frequency. In preterm neonates, average nightly sleep and
      average daily sleep of all recorded days were very similar, but after the fourth
      day of life, only average nightly sleep increased. In full-term neonates, average
      nightly and daily sleep time of all recorded days differed by about 1h. Average
      sleep time during 24h for preterm and full-term neonates was similar. Preterm
      neonates showed longer intervals between events of food intake than full-term
      neonates. The circadian peaks in the frequency spectra of full-term neonates may
      indicate the initial adaptation in the first week of life to a 24h day. This is
      in agreement with our results concerning the different durations of nightly and
      daily sleep. The increase in nightly sleep time of preterm neonates may be
      attributed to the progressing adaptation to a circadian activity-rest pattern.

PMID- 11587092
TI  - Circadian rhythms of basic fibroblast growth factor (bFGF), epidermal growth
      factor (EGF), insulin-like growth factor-1 (IGF-1), insulin-like growth factor
      binding protein-3 (IGFBP-3), cortisol, and melatonin in women with breast cancer.
AB  - BACKGROUND: Circadian rhythms in plasma concentrations of many hormones and
      cytokines determine their effects on target cells. METHODS: Circadian variations
      were studied in cortisol, melatonin, cytokines (basic fibroblast growth factor
      IbFGF], EGF, insulin-like growth factor-1 [IGF-1]), and a cytokine receptor
      (insulin-like growth factor binding protein-3 [IGFBP-3]) in the plasma of 28
      patients with metastatic breast cancer. All patients followed a diurnal activity
      pattern. Blood was drawn at 3h intervals during waking hours and once during the
      night, at 03:00. The plasma levels obtained by enzyme-linked immunoassay (ELISA)
      or radioimmunoassay (RIA) were evaluated by population mean cosinor (using local
      midnight as the phase reference) and by one-way analysis of variance (ANOVA).
      RESULTS: Cortisol and melatonin showed a high-amplitude circadian rhythm and a
      superimposed 12h frequency. bFGF showed a circadian rhythm with an acrophase
      around 13:00 with a peak-to-trough interval (double amplitude) of 18.2% and a
      superimposed 12h frequency. EGF showed a circadian rhythm with an acrophase
      around 14:20, a peak-to-trough interval of 25.8%, and a superimposed 12h
      frequency. IGF-1 showed a high value in the morning, which is statistically
      different (t test) from the low value at 10:00, but a regular circadian or
      ultradian rhythm was not recognizable as a group phenomenon. IGFBP-3 showed a low
      amplitude (peak-to-trough difference 8.4%) circadian rhythm with the acrophase
      around 11:00 and low values during the night. CONCLUSIONS: (1) Circadian
      periodicity is maintained in hospitalized patients with metastatic breast cancer.
      (2) Ultradian (12h) variations were superimposed on the circadian rhythms of the
      hormones and several of the cytokines measured. (3) Studies of hormones and
      cytokines in cancer patients have to take their biologic rhythms into
      consideration. (4) The circadian periodicity of tumor growth stimulating or
      restraining factors raises questions about circadian and/or ultradian variations
      in the pathophysiology of breast cancer.

PMID- 11587093
TI  - Cyclic red blood cell destruction in thalassemia.
AB  - A retrospective analysis of time series of hemoglobin (Hb) destruction of 24
      children (11 males and 13 females) with thalassemia from the age of 6 to 12 years
      showed that the Hb destruction rate typically oscillated with an average period
      of 50 days. A possible relation between the periodism and the severity of the
      disease is also suggested.

PMID- 11587094
TI  - Interstitial lung diseases: what next?

PMID- 11587095
TI  - Drug-induced pneumonitis: the role of methotrexate.
AB  - Methotrexate (MTX) is a folate antagonist used in several chronic inflammatory
      and neoplastic conditions. Pulmonary toxicity occurs in 0.5% to 14% of patients
      receiving low-dose MTX. Manifestations of pulmonary toxicity are protean and
      include parenchymal inflammation, pneumonia, airway hyperreactivity, air trapping
      and possibly neoplasm. We performed an exhaustive review of the English
      literature and identified 189 cases of methotrexate-induced pneumonitis (MIP).
      Rheumatoid arthritis (RA) was the most frequent underlying disease. In most
      patients, symptoms present subacutely with progression over several weeks. Most
      patients present with dyspnea, dry cough, fever, and bibasilar crackles.
      Peripheral eosinophilia has been cited in one third of cases. The chest
      radiograph may be normal, but more commonly reveals bilateral interstitial or
      mixed, interstitial and alveolar infiltrates with a predilection for the bases.
      Chest computed tomography (CT) scans demonstrate ground-glass opacities,
      interstitial infiltrates, septal lines or widespread consolidation. Pulmonary
      function studies reveal a restrictive ventilatory defect and/or impaired gas
      exchange. Bronchoalveolar lavage (BAL) may be helpful in ruling out an infectious
      etiology and in supporting the diagnosis of MIP. Cellular interstitial
      infiltrates, granulomas, fibrosis, atypical epithelial cells, and diffuse
      alveolar damage (DAD) are the main histologic features. Once MIP is suspected,
      the MTX should be withdrawn. Corticosteroids may accelerate resolution and are
      recommended in severe or fulminant cases. The prognosis of MIP is usually
      favorable, but occasionally the outcome may be fatal.

PMID- 11587097
TI  - Induced sputum: opening a new window to the lung.
AB  - The interest in sputum assessment as a non-invasive technique to retrieve cells
      and soluble material from the lung has increased and gained momentum during the
      last decade. As a marker of inflammation in airway diseases, induced sputum (IS)
      is a particularly promising procedure since it provides specific information on
      both the cellular and molecular constituents in inflammation. From 1950-1970,
      sputum cells had been examined on stained smears, with the procedure having been
      applied in both research and clinical settings. After having been recovered by
      spontaneous coughing, the cells were used to study lung cancer and respiratory
      infections and, later on, to diagnose Pneumocystis carinii pneumonia in patients
      infected with human immuno-deficiency virus (HIV). The method was widely improved
      upon by the induction of sputum with aerosol of hypertonic saline and then
      extended to become part of the assessment of airway inflammation in bronchial
      asthma and chronic obstructive pulmonary disease (COPD). It was recently shown
      that IS can be used to study interstitial lung diseases (ILD) and, more
      specifically, pneumoconiosis, sarcoidosis, non-granulomatous ILD and occupational
      lung diseases. In light of the fact that immunologic and functional
      bronchopulmonary abnormalities may be present in up to two-thirds of patients
      with Crohn's disease, we studied the use of IS in this condition as well. This
      review analyzes the value of IS and its present applications in pulmonary
      medicine.

PMID- 11587096
TI  - Pulmonary Langerhans cell Histiocytosis.
AB  - Pulmonary Langerhans cell Histiocytosis is a rare granulomatous disease affecting
      both sexes, with greater incidence in the second and third decades of life;
      smoking appears to be the most important risk factor. Its etiology is unknown,
      although there are data indicating an uncontrolled immune response as possible
      cause, sustained by the Langerhans cells, antigen presenting cells for T
      lymphocytes, and their accumulation in the distal bronchioles; these cells
      express on their surface the CD1a and CD1c antigens, and the B7 molecule,
      essential for activating quiescent T lymphocytes. In its evolution the granuloma
      is characterized by the progressive reduction in the LC number, with the increase
      of fibrosis, surrounding and destroying the bronchiolar lumen; the remaining of
      the lumen, or the traction exerted by fibrous tissue on the adjacent alveolar
      spaces leads to the cyst development. Vascular involvement occurs frequently, and
      may explain the onset of pulmonary hypertension in advanced cases of the disease.
      The disease may be asymptomatic, or it may present with aspecific respiratory
      signs and symptoms, and has characteristic radiological findings, being included
      in the group of cysticaerial parenchymal alterations. The diagnosis could be
      suggested by the finding of a number of LC in BAL greater than 5%. Different
      therapies have been proposed, but it seems that the most important measure is
      smoking cessation.

PMID- 11587098
TI  - Significance of increase in lipocortin-1 gene transcripts in the blood monocytes
      of patients with pulmonary sarcoidosis.
AB  - BACKGROUND AND AIM OF THE WORK: Lipocortin-1 (also known as annexin-1) is
      upregulated by corticosteroids and plays a prominent part in many of their anti
      inflammatory actions. In our previou investigation, lipocortin-1 gene expression
      in blood monocytes was higher in sarcoidosis patients tha in healthy subjects or
      IPF patients. In this study, we examined the amounts of lipocortin-1 gene tran
      scripts [at baseline and after stimulation by synthetic adrenocorticotrophic
      hormone (ACTH)] in the blood monocytes of sarcoidosis patients, and then we
      analyzed the relationships between these amount and several clinical indexes.
      METHODS: Serum and blood monocyte samples were prepared from 21 sar coidosis
      patients before and after ACTH stimulation. The amounts of lipocortin-1 and beta
      actin gene tran scripts obtained from monocytes were quantified by RT-PCR. The
      patients were prospectively followe for at least 2.5 years. RESULTS: 1. Serum
      cortisol was increased in all patients after synthetic ACTH in jection. 2.
      Lipocortin-1 gene transcripts tended to increase in parallel with increases in
      serum cortisol but the relationship was not significant. 3. The amounts of
      lipocortin-1 gene transcripts induced by syn thetic ACTH were related to two
      indexes of disease activity/extension: the presence of parenchymal lesions (p =
      0.018), and the presence of extrathoracic lesions (p = 0.043). 4. After 3 years
      of follow-up the patients with higher basal amounts of lipocortin-1 gene
      transcripts in monocytes showed improve ment of sACE activity and FEV1/FVC%.
      CONCLUSION: The amounts of lipocortin-1 gene transcripts induced by synthetic
      ACTH were related to the presence of parenchymal lesions, while their basa
      amounts correlated with either improvement of sACE activity or stabilization of
      FEV1/FVC%.

PMID- 11587099
TI  - Evidence for disease phenotype associated haplotypes (DR.TNF) in sarcoidosis.
AB  - BACKGROUND AND AIM OF THE WORK: In a previous study, gene polymorphisms of the
      MHC locus (-308 TNFalpha promotor, HLA-DR) in patients with pulmonary sarcoidosis
      had been investigated and significant correlations with the presentation of the
      disease as defined by the presence of Lofgren syndrome had been found. Since
      genotyping of both loci was necessary to reveal a significant difference on the
      genetic level between the two patient groups Lofgren and non-Lofgren, a working
      hypothesis was derived in which a disease course associated haplotype, rather
      than single specific genes, was considered to play a role in the pathogenesis of
      sarcoidosis. METHODS: A first step to test this hypothesis was taken by
      calculating virtual haplotypes from these previous data. Statistical analysis of
      disease phenotype association and relative risk of these virtual haplotypes was
      performed to assess correlations with sarcoidosis and the two disease phenotypes.
      RESULTS: The results not only substantiated the previous findings, but also
      showed that the virtual haplotype DR3.TNFalpha2 was significantly associated with
      Lofgren syndrome and that the virtual haplotype DR2.TNFalpha1 was noticeably
      although not significantly associated with the non-Lofgren patients. CONCLUSIONS:
      Using theoretical calculations based on actual data, haplotypes, rather than
      single genes interacting with each other, were found to be a highly likely
      explanation for the previously published observations. In addition, the results
      allow the conclusion to be drawn that disease course associated haplotypes in
      sarcoidosis are highly probable and that further investigation of polymorphisms
      in the MHC gene region holds the potential of defining prognostic markers.

PMID- 11587100
TI  - ECG-abnormalities in Japanese and Swedish patients with sarcoidosis. A
      comparison.
AB  - BACKGROUND AND AIM OF THE WORK: ECG abnormalities are more common in patients
      with sarcoidosis than in controls. The incidence of cardiac sarcoid granulomas in
      the Japanese population has been found to be higher than that seen in Caucasians.
      We compared the prevalence of ECG abnormalities in Japanese and Swedish patients
      with sarcoidosis. METHODS: Twelve-lead routine ECG's were compared between
      consecutive patients (134 Japanese and 149 Swedish) of similar age with
      histologically verified sarcoidosis or a high clinical probability of the disease
      and a history of no more than 12 months before the ECG. RESULTS: There was no
      statistically significant difference in the prevalence of first degree AV block,
      ST-T-segment abnormalities, right bundle branch block (RBBB) and left anterior
      block (LAH) in Japanese and Swedish patients. Among the Swedes, the results were
      compared with those of a smaller group (n = 29) of older patients with a longer
      disease course. In these few patients LAH and RBBB occurred more frequently than
      in patients with a recent diagnosis. CONCLUSIONS: ECG abnormalities in patients
      with sarcoidosis seem to be of similar frequency in Japan and Sweden. ST-T
      changes and first degree AV block would appear early in the course of the
      disease, whereas more pronounced conduction defects may appear later.

PMID- 11587101
TI  - Is it necessary to treat all patients with idiopathic pulmonary fibrosis?
AB  - BACKGROUND AND AIM OF THE WORK: To investigate the clinical course of untreated
      patients with idiopathic pulmonary fibrosis (usual interstitial pneumonia)
      (IPF/UIP). METHODS: Forty-three patients with IPF/UIP, divided into two groups.
      Group I consisted of 29 patients treated at diagnosis, while Group II comprised
      14 patients who did not receive treatment. The indication of treatment was
      established whenever patients referred to a significant progression of the degree
      of dyspnea during the year prior to diagnosis. RESULTS: At diagnosis, patients
      from Group I had lower FVC (mean +/- SEM, 56+/-3% vs 73+/-3%) (p = 0.0004) and a
      greater extent of ground glass pattern in high resolution CT scan (18+/-4% vs 4+/
      1%) (p = 0.004) than those from Group II. In group I, a follow-up study was
      carried out on 26 patients for 24+/-4 months. Thirteen of these 26 patients (50%)
      died 11+/-4 months after the initial assessment. Serial pulmonary functional
      tests were performed on 19 patients. Thirteen patients from Group II were
      followed up for 23+/-3 months. Seven of these 13 patients were treated 12+/-3
      months after the diagnosis because of progression of the disease. The remaining 6
      patients remained untreated and with the disease stable at the end of the follow
      up, representing 15% (6 out of 39) of the whole study group. No patients from
      this group died during the follow-up. At the end of the follow-up, there were no
      differences in lung function changes between treated patients (19 from Group I
      and 7 from Group II), and the 6 untreated patients. CONCLUSIONS: Some patients
      with IPF/UIP remain stable for extended periods of time without treatment.

PMID- 11587102
TI  - Carpal tunnel syndrome in sarcoidosis.
AB  - Sarcoidosis is a systemic disease that may affect the musculoskeletal system. An
      association between carpal tunnel syndrome (CTS) and sarcoidosis has not been
      demonstrated. Consecutive patients from the sarcoidosis clinic at our institution
      were questioned about history and symptoms of carpal tunnel syndrome: hand
      numbness and nocturnal paresthesias with relief of symptoms by shaking of the
      hands (flick sign). A physical exam was performed to evaluate for Tinel's and
      Phalen's signs. A comparison of the presence of arthritis, prednisone treatment,
      spirometry, and number of organs involved with sarcoidosis was made in patients
      with a history or clinical findings of CTS versus those without. Eighty-nine
      patients were evaluated. Thirty-five patients (39%) had nocturnal paresthesias
      with a positive flick sign. Fourteen patients (16%) had physical findings of CTS.
      A history of CTS was present in 14 (16%) of the patients, four of which were
      documented by EMG. There was no significant difference between the frequency of
      prednisone treatment in patients with or without CTS history, nocturnal
      paresthesias, or Phalen's sign. There were significantly fewer patients with a
      positive Tinel's sign who were receiving prednisone. There was a trend toward an
      increased frequency of wrist arthritis in patients with a history or clinical
      findings of CTS. There was no significant difference in disease severity,
      assessed by spirometry or organ involvement, when comparing sarcoidosis patients
      with or without a history or clinical findings of CTS. Thirty-nine (44%) had
      symptoms and/or signs of CTS. Even when we adjusted our sarcoidosis population
      for other factors associated with CTS, the prevalence of symptoms and signs of
      CTS was much higher in our patient population than in studies of the general
      population. Our findings suggest that CTS is common in sarcoidosis.

PMID- 11587103
TI  - Breast disease in sarcoidosis.
AB  - BACKGROUND: Breast disease in sarcoidosis can be classified as sarcoidosis
      patients with breast granulomas, sarcoidosis patients with breast cancer, and
      breast cancer patients displaying sarcoidosis-like breast reactions. METHODS: We
      reviewed the medical records of 629 women with sarcoidosis followed in the
      Interstitial Lung Disease Clinic at the University of Cincinnati for findings
      associated with breast disease. In addition, three women with breast cancer who
      had granulomas in proximity to their tumors were also examined. RESULTS: Abnormal
      breast examinations or mammograms were reported in 15 patients with sarcoidosis
      (2% of women with sarcoidosis). Breast biopsy revealed granulomas consistent with
      sarcoidosis in six. One of them developed breast cancer five years later. Breast
      cancer was identified in twelve further patients, therefore a total of thirteen
      patients with breast cancer were identified. Ten were diagnosed with breast
      cancer plus sarcoidosis: sarcoidosis preceded breast cancer in three, followed
      breast cancer in five, the two diseases appeared simultaneously in two. Three
      additional women with breast cancer were also evaluated and classified as
      patients with sarcoid-like reaction. Review of the mammographic and physical
      findings could not distinguish between sarcoidosis in the breast and breast
      cancer. CONCLUSION: Sarcoidosis patients develop breast cancer at the expected
      frequency. The breast cancer diagnosis may precede or follow that of sarcoidosis.
      There is no relationship between stage of sarcoidosis or treatment and the
      development of cancer. Because physical examination and mammography findings are
      unable to distinguish between sarcoidosis and malignancy, biopsy of all
      suspicious lesions in sarcoidosis is recommended.

PMID- 11587104
TI  - Pioneers of sarcoidosis: Caesar Peter Moeller Broeck (1845-1917).

PMID- 11587105
TI  - Extended genetic alterations in a patient with pulmonary sarcoidosis, a benign
      disease.
AB  - BACKGROUND: Genetic alterations at the microsatellite level have been detected in
      various human malignant tissues, but have also been found in chronically inflamed
      tissues. Sarcoidosis is a benign disease of unknown etiology characterized by
      chronic inflammation, which may be associated with an increased incidence of
      developing malignancy. METHODS: We examined the microsatellite alterations in a
      sputum cytological specimen of a patient with sarcoidosis. The DNA
      electrophoretic pattern of sputum was compared with that of the peripheral blood.
      Thirty-two microsatellite markers located at chromosomes 2p, 3p, 8p, 9p, 9q, 17p,
      17q were used to reveal genetic alterations. RESULTS: Loss of heterozygosity
      (LOH) was detected in eleven markers in loci 2p, 9p, 9q and 17q. LOH was observed
      in all four markers spanning the chromosomal arm 17q11.2-q21, suggesting a
      potential chromosomal deletion. CONCLUSION: The observation of LOH in all four
      markers spanning the chromosomal arm 17q11.2-q21 may suggest a potential for
      malignancy development in this patient, or may be linked to the aetiopathogenesis
      of sarcoidosis. Further microsatellite fine mapping and clinical follow up of
      this patient are needed to clarify this.

PMID- 11587106
TI  - Bronchoalveolar lavage suggesting diffuse alveolar damage in a patient with acute
      eosinophilic pneumonia.

PMID- 11587107
TI  - Prolonged survival of a bare lymphocyte syndrome type I patient with diffuse
      panbronchiolitis treated with erythromycin.

PMID- 11587108
TI  - A biopsychosocial overview of pretreatment screening of patients with pain.
AB  - The prevalence and excessive cost of pain, especially when the pain becomes
      chronic, remains a major health-care problem in the United States. Currently, a
      biopsychosocial perspective of pain has been found to be the most heuristic
      approach to understanding and managing it. Using this perspective, an important
      advance has been made in the possibility of individually tailoring treatment for
      each patient, with the result being better outcomes. The author reviews the
      extant literature demonstrating a robust "psychosocial disability factor" among
      injured workers that is important not only in pain perception, but also in the
      subsequent development of chronic pain-related disability. Such results emphasize
      the importance of taking into account how psychosocial and physical factors are
      intertwined in a complex way in determining pain symptomatology. On the basis of
      these findings, a number of surgical pre-screening approaches have been developed
      and found to be effective for maximizing surgical outcomes as described by
      Carragee, Epker, and Block in other papers in this special topics series.
      Recently, several organizations in the U.S. have also developed new standards for
      the evaluation of pain. For example, the Joint Commission on Accreditation of
      Health Organizations (JCAHO) now requires that physicians consider pain as a "5th
      vital sign" in evaluating patients. Such initiatives have created a new mandate
      to regularly assess and manage all types of pain. The use of opioids, as well as
      implantable pain-management modalities, are among the options. The author notes
      that the literature on these modalities focuses on interdisciplinary patient
      screening approaches prior to their administration as a way of maximizing
      treatment outcomes. The papers by Praeger, Jacobs, and Robinson et al. in this
      special topics series describe the approach to pretreatment assessment for these
      modalities in detail. Finally, the author presents a stepwise, biopsychosocial
      approach as the basis for assessment before decisions regarding surgery, opioid
      maintenance therapy, and implantable pain-management modalities. The author
      suggests that systematic pretreatment interventions will facilitate a more
      structured standard of care in the evaluation and treatment of patients with pain
      and ultimately better outcomes.

PMID- 11587109
TI  - Presurgical psychological screening in back pain patients: a review.
AB  - OBJECTIVE: The objective of this article is to provide a brief overview of the
      major psychosocial risk factors impacting recovery from spine surgery. RESULTS:
      Numerous personality, cognitive, behavioral and historical factors affecting
      surgical recovery are reviewed. Among the most significant issues that have been
      found to have an adverse influence on outcome are Minnesota Multiphasic
      Personality Inventory scale elevations associated with pain sensitivity,
      depression, anger and anxiety. Maladaptive pain coping strategies, litigation,
      workers' compensation and reinforcement of pain behavior by the spouse also have
      been found to reduce spine surgery results. A number of other factors are
      reviewed, including pre-existing psychological problems, sexual and physical
      abuse, marital distress and substance abuse. CONCLUSIONS: Presurgical
      psychological screening should be included in the medical diagnostic process of
      spine surgery candidates, especially when the major goal is pain reduction, or
      when the surgeon recognizes the existence of psychosocial risk factors.
      Suggestions for future directions in the development of presurgical psychological
      screening procedures are also given.

PMID- 11587110
TI  - Evaluation of patients for implantable pain modalities: medical and behavioral
      assessment.
AB  - BACKGROUND: Advances in neurobiology serve as the basis for current and evolving
      implantable pain modalities, consisting of neurostimulation and neuraxial drug
      administration systems. Appropriate treatment of pain begins with an accurate
      diagnosis based on thorough physical and behavioral evaluations. MEASURES: The
      medical evaluation includes a review of the patient's medical history, diagnostic
      studies, physical examination, complete diagnostic workup, and screening trial of
      the proposed implantable therapy. The behavioral evaluation includes a review of
      the patient's history and medical records, clinical interview, mental status
      examination, psychological testing, and determination of suitability for
      implantation. CONCLUSIONS: Patients with chronic pain are subject to
      neurophysiological, emotional, and behavioral influences that govern their
      perception of pain and of pain relief. Therefore, treatment of chronic pain is
      multidisciplinary, drawing on cognitive and behavioral psychological therapies,
      functional rehabilitation, orthopedic and neurologic surgery, medications, nerve
      blockade, neuroaugmentative procedures, and sometimes neurodestructive
      procedures. Appropriate selection of patients helps ensure that implantable
      therapies are used for those who are most likely to benefit.

PMID- 11587111
TI  - Psychological screening in the surgical treatment of lumbar disc herniation.
AB  - The specific use of psychological screenings to determine appropriateness for
      lumbar discectomy surgery and predict outcomes is not well understood. Data from
      spine surgery as a whole are not likely generalizable to the patient with a
      significant disc herniation considering surgery. As opposed to most "back pain
      syndromes," acute and subacute sciatica from disc hemiation has a very high
      chance of dramatic and lasting improvement with surgery. Recent studies have
      shown standard psychometric tests used as preoperative screening in this
      situations fail to predict outcomes in most subgroups. Data from the author's
      institution suggest severe emotional distress in those patients coming to early
      surgical intervention does not correlate with adverse outcomes. However, the same
      psychometric profile in those patients with chronic sciatica pain and disability
      does predict worse outcomes compared with chronic pain in less emotionally
      distressed patients. The data suggest that the ability to rapidly relieve pain in
      the case of disc herniation may limit the morbid effects of psychological
      distress seen in many back pain syndromes. With prolonged pain and emotional
      distress, however, adverse and possibly self-perpetuating psychological and
      social changes may significantly decrease the impact of disc surgery.

PMID- 11587112
TI  - Screening for problematic prescription opioid use.
AB  - The proper medicinal use of opioids, in light of their notorious history and
      current relation to social ills, continues to be debated and remains unclear in
      several areas of medicine. This article will review several areas and points of
      controversy related to screening for potential problematic opioid behavior in
      chronic nonmalignant pain patients. Controversy over the prescription of opioids
      for chronic nonmalignant pain continues, despite the growing acceptance of this
      practice. Indeed, past research supports the beneficial use of opioids for
      noncancer pain. Unfortunately, traditional definitions of abuse and dependence,
      with their emphasis on tolerance and withdrawal, are inappropriate for chronic
      pain patients prescribed opioids. The component of traditional definitions of
      abuse and dependence that appears most applicable to chronic pain patients
      centers on the criterion that the patient continue to take the drug (in this
      case, the opioid) despite negative and harmful effects or despite any decrease in
      pain level. Although clinical observations exist about risk factors for opioid
      misuse in chronic pain patients, there is limited research. Further, the area of
      prescreening for problematic drug behavior is in its infancy. However,
      researchers have begun to delve into this challenging area and the application of
      rigorous empirical research will bring us closer to identifying those patients at
      risk so that their pain is managed without destructive outcomes in other areas of
      their life.

PMID- 11587113
TI  - Effectiveness of virtual reality-based pain control with multiple treatments.
AB  - OBJECTIVE: The current study explored whether immersive virtual reality continues
      to reduce pain (via distraction) with repeated use. SETTING: The study was
      conducted in a burn care unit at a regional trauma center. PATIENTS: Seven
      patients aged 9-32 years (mean age of 21.9 years; average of 23.7% total body
      surface area burned [range, 3-60%]) performed range-of-motion exercises of their
      injured extremity under an occupational therapist's direction on at least 3
      separate days each. INTERVENTION: For each physical therapy session, each patient
      spent equal amounts of time in virtual reality and in the control condition (no
      distraction). The mean duration of physical therapy in virtual reality was 3.5,
      4.9, and 6.4 minutes for the first, second, and third session, respectively.
      Condition order was randomized and counter-balanced. OUTCOME MEASURES: For each
      of the three physical therapy sessions, five visual analog pain scores for each
      treatment condition served as the dependent variables. RESULTS: Pain ratings were
      statistically lower when patients were in virtual reality, and the magnitude of
      pain reduction did not diminish with repeated use of virtual reality. The results
      of this study may be examined in more detail at www.vrpain.com. CONCLUSIONS:
      Although the small sample size limits generalizability. results provide
      converging preliminary evidence that virtual reality can function as a strong
      nonpharmacological pain reduction technique for burn patients during physical
      therapy. Results suggest that virtual reality does not diminish in analgesic
      effectiveness with three (and possibly more) uses. Virtual reality may also have
      analgesic potential for other painful procedures or pain populations. Practical
      implications are discussed.

PMID- 11587114
TI  - Polycythemia vera presenting as complex regional pain syndrome of the lower
      limbs.
AB  - CASE REPORT: A 73-year-old woman with bilateral severe pain in her legs and feet
      was admitted to the hospital. The pain had started spontaneously without any
      known trauma a year earlier and had progressively worsened to the point that she
      was unable to walk. The patient complained of pain, discoloration, and sweating
      of the lower extremities. Physical examination revealed swollen, cold, wet, and
      blue extremities, with both allodynia and hyperalgesia, fulfilling criteria for a
      diagnosis of complex regional pain syndrome (CRPS) type 1. Laboratory findings
      demonstrated a hemoglobin level of 180 g/L(-1) and a hematocrit of 47%, leading
      to a diagnosis of polycythemia vera (PCV). Her condition slowly improved after
      repeated venesection, mild analgesics, and amitriptyline. CONCLUSIONS:
      Polycythemia vera has not been described previously as a contributing factor in
      CRPS. In the present case, the diagnosis of PCV was important, because its
      treatment also improved the CRPS.

PMID- 11587115
TI  - Stability, compatibility, and safety of intrathecal bupivacaine administered
      chronically via an implantable delivery system.
AB  - OBJECTIVE: The only agent approved by the U.S. Food and Drug Administration for
      chronic intrathecal infusion for the treatment of chronic pain is morphine
      sulfate. In patients who do not experience adequate relief from intrathecal
      opioids, bupivacaine is frequently added to increase efficacy. The studies
      reported here were conducted to demonstrate the stability and compatibility of
      bupivacaine in a commonly used implantable infusion system and the long-term
      clinical safety of this therapy. METHODS: A commercially available bupivacaine
      solution (7.5 mg/ml) was incubated at 37 degrees C for 12 weeks with intact
      delivery systems and with the individual materials that comprise the fluid
      pathway. Intermittent samples were collected and analyzed using liquid
      chromatography. Materials chronically exposed to bupivacaine were analyzed for
      mechanical integrity. One hundred eight patients treated with intrathecal
      bupivacaine (average dose: 10 mg/d, range: 2-25 mg/d) and opioids for an average
      duration of 86 weeks were monitored clinically (patient interviews and neurologic
      examinations) approximately every 4 weeks. RESULTS: Bupivacaine concentrations
      remained greater than 96% of the starting material after chronic exposure to the
      delivery system materials or the intact pump-catheter systems. and the mechanical
      integrity of the delivery system and materials remained intact. When combined
      with intrathecal morphine or hydromorphone, no clinical evidence of drug-induced
      toxicity or complications was observed in any patient. Supplementing opioid
      therapy with bupivacaine allowed the pain patient to continue to be effectively
      managed using an implantable intrathecal delivery system. CONCLUSIONS:
      Bupivacaine is stable and compatible with a commonly used implantable drug
      infusion system. In this study, chronic supplementation of intrathecal opioids
      with bupivacaine was a safe method for providing continued management of chronic
      pain of cancer or noncancer origin.

PMID- 11587116
TI  - Preliminary study of chronic pain patients' concerns about cannabinoids as
      analgesics.
AB  - OBJECTIVE: This was a preliminary investigation of patients' beliefs about
      cannabinoids and the associations between those beliefs, beliefs about
      medication, and personal and pain variables with regard to patients' willingness
      to try cannabinoids as analgesics. DESIGN: A self-completion questionnaire was
      used. SETTING: The investigation took place in an outpatient pain clinic.
      PATIENTS: Sixty-seven patients with chronic pain were involved. OUTCOME MEASURES:
      The outcome measures were patients' stated willingness to use cannabinoids and
      the extent of their agreement or disagreement with statements concerning
      cannabinoids and medicines in general. RESULTS: Fifty-two percent of patients
      were doubtful about taking cannabinoids: unwillingness was strongly associated
      with specific concerns about side effects, addiction, tolerance, and losing
      control but not with general beliefs about medication or personal or medical
      variables other than age. CONCLUSIONS: The concerns of patients with chronic pain
      about taking cannabinoids as analgesics may reduce their utility and efficacy;
      accurate information is required to counter this effect.

PMID- 11587117
TI  - A comparison of blacks and whites seeking treatment for chronic pain.
AB  - OBJECTIVE: Most conceptualizations of chronic pain acknowledge the importance of
      culture and social circumstances. Cultural and social influences may differ for
      persons of different racial or ethnic groups, and this circumstance may lead them
      to experience and adjust differently to pain. The current study compared
      adjustment to chronic pain by blacks and whites seeking treatment for chronic
      pain. SUBJECTS AND MEASURES: Fifty-seven black and 207 white patients completed
      measures of anxiety, depression, disability, pain, and physical symptoms during
      their initial visit to a university pain clinic. RESULTS: Comparisons showed that
      the groups did not differ with regard to age, sex, education, chronicity of pain,
      pain location, work status, previous surgeries, medical diagnosis, medication,
      wage replacement, or involvement in litigation. However, the black group reported
      higher pain severity, more avoidance of activity, more fearful thinking, more
      physical symptoms, and greater physical and psychosocial disability. The groups
      remained significantly different with regard to avoidance, fearful thinking, and
      physical symptoms after pain severity was statistically controlled for; however,
      they did not remain different on disability. CONCLUSIONS: These results show that
      blacks and whites with chronic pain experience pain differently. Several factors
      may underlie these differences, including family situation, health care
      experiences, or other unmeasured behavioral, environmental, or social influences.
      Other investigators should attempt to replicate these findings and more closely
      examine variables that may explain them.

PMID- 11587118
TI  - How effective is the acute low back pain screening questionnaire for predicting 1
      year follow-up in patients with low back pain?
AB  - OBJECTIVES: The aim of this study was to investigate potential associations
      between the Acute Low Back Pain Screening Questionnaire (ALBPSQ), a
      biopsychosocial screening instrument for identifying patients at risk of
      chronicity, and relevant variables at 1-year follow-up in a cohort of patients
      with low back pain. STUDY DESIGN: A 1-year prospective study was conducted in
      which patients who had previously received treatment in the Northern Ireland
      National Health Service (n = 118) were requested to complete a follow-up
      questionnaire package of pain and functional disability measures and a patient
      centered questionnaire of seven variables considered relevant from the patient's
      perspective. PATIENTS: Ninety patients (76% response rate) returned the completed
      questionnaire package. RESULTS: The ALBPSQ total score and cutoff score of 112
      were significantly positively associated with the pain and functional disability
      questionnaire scores at follow-up but did not significantly discriminate for
      difference scores on these measures. Although six of the seven patient-centered
      variables were significantly associated with the screening questionnaire total
      score, the cutoff score was strongly predictive of only one variable (work loss)
      and failed to demonstrate high levels of sensitivity for other variables (i.e.,
      medication use, additional treatment, poor exercise participation). CONCLUSIONS:
      The findings of this study demonstrate that scores on the ALBPSQ were positively
      correlated with patients' levels of pain and functional disability at 1-year
      follow-up and correctly classified all patients reporting some degree of work
      loss but had minimal predictive strength for the other patient-centered variables
      evaluated.

PMID- 11587119
TI  - Validation of the WHOQOL-100: pain management improves quality of life for
      chronic pain patients.
AB  - OBJECTIVE: The study aimed to validate a new, multidimensional, multilingual
      instrument (the WHOQOL-100) for assessing QOL in chronic pain patients. METHODS:
      Chronic pain patients (N = 106) who agreed to participate in an established pain
      management program (PMP) were assessed for quality of life (QOL) before and one
      month after the intervention. The WHOQOL-100 is a generic profile containing 25
      facets of QOL organized in 6 domains. It was administered concurrently with the
      MOS Short Form-36, the Beck Depression Inventory, and measures of pain intensity,
      duration, disruption and distress. RESULTS: The patients were outpatients and
      inpatients with a mean age of 44 years and mean pain duration of 8 years. The
      sample included 70 (66%) women. After the PMP, QOL had significantly improved
      generally. and in the physical, psychological and independence domains, as well
      as in 10 facets of QOL including pain and discomfort. Good QOL is consistently
      associated with low levels of pain severity and pain distress and little pain
      disruption. Overall internal consistency reliability was good and for most facets
      and domains but marginal for the pain facet. When compared with the SF-36. the
      WHOQOL-100 shows good concurrent validity, greater comprehensiveness and very
      good responsiveness to clinical change. DISCUSSION: The WHOQOL-100 indicates
      significant improvements to QOL for those entering a PMP and is validated for the
      clinical assessment of chronic pain patients and for use in multi-national
      clinical trials, clinical governance and audit.

PMID- 11587120
TI  - Minimal acupuncture may not always minimize specific effects of needling.

PMID- 11587121
TI  - Nonpharmacologic treatment of musculoskeletal disease.

PMID- 11587122
TI  - Measurement of cardiac troponins.
AB  - The cardiac troponins form part of the regulatory mechanism for muscle
      contraction. Specific cardiac isoforms of cardiac troponin T and cardiac troponin
      I exist and commercially available immunoassay systems have been developed for
      their measurement. A large number of clinical and analytical studies have been
      performed and the measurement of cardiac troponins is now considered the 'gold
      standard' biochemical test for diagnosis of myocardial damage. There have been
      advances in understanding the development and structure of troponins and their
      degradation following myocardial cell necrosis. This has contributed to the
      understanding of the problems with current assays. Greater clinical use has also
      highlighted areas of analytical and clinical confusion. The assays are reviewed
      based on manufacturers' information, current published material as well as the
      authors' in-house experience.

PMID- 11587123
TI  - Assessment of adult phenylketonuria.
AB  - Phenylketonuria (PKU) has been detected on the newborn screening programme since
      the 1960s. Although it is recognised that dietary treatment is successful in
      avoiding the severe mental retardation associated with untreated PKU, the long
      term outcome for adults remains unclear. The Medical Research Council recommends
      that the diet be followed for life. This paper discusses the relevance of the
      findings of neurological deterioration, neuropsychological problems and brain
      imaging in adults with PKU. It suggests an approach to follow-up for adults with
      PKU including neurological assessments, awareness of nutritional deficiencies,
      educational requirements and the risks of maternal PKU.

PMID- 11587124
TI  - Diagnosis and clinical biochemistry of inherited tubulopathies.
AB  - Epithelial ion channels and transporter proteins have physiologically important
      roles throughout the length of the nephron. Discovering the molecular identities
      of tubular epithelial cell proteins and their functional roles has increased
      understanding of both renal physiology and tubular diseases. Defects in tubular
      handling of solutes may present with nephrocalcinosis or nephrolithiasis,
      rickets, acid base, electrolyte or blood pressure disturbances. Biochemical
      analysis of both serum and urine, together with clinical history and examination,
      remain fundamental for their diagnosis, whilst understanding of underlying
      molecular mechanisms allows appropriate management.

PMID- 11587125
TI  - Growth hormone: its measurement and the need for assay harmonization.
AB  - Serum human growth hormone (hGH) assays show a wide range in bias and in cut-off
      values for provocative tests, which vary from 13.5 to 35-40 mU/L when they have
      been established. Studies using novel hGH assays show that methods that are
      absolutely specific for 22-kDa hGH may not identify bioactive hGH peaks and that
      20:22-kDa hGH ratios are increased in acromegaly. Greater harmonization of serum
      hGH methods can be achieved by: changing from IS 80/505 to IS 98/574, which is
      calibrated in mass units of recombinant 22-kDa hGH; using monoclonal/polyclonal
      or polyclonal/polyclonal antibody combinations that measure both 20-kDa and 22
      kDa hGH; the development of assays such as the immunofunctional hGH assay which
      has the convenience of an immunometric assay but gives results that correlate
      better with bioassays collaboration between manufacturers and laboratories to
      establish method-related cut-off limits for provocative tests of hGH status.

PMID- 11587126
TI  - Procalcitonin as an acute phase marker.
AB  - Procalcitonin is a 14-kDa protein encoded by the Calc-1 gene along with
      calcitonin and katacalcin. The function and regulation of this protein are quite
      different from those of the other gene products. Blood concentrations of
      procalcitonin are increased in systemic inflammation, especially when this is
      caused by bacterial infection. Studies of its behaviour in patients with
      bacterial sepsis have led to the proposal that it may be a useful marker of
      systemic bacterial infection, with greater specificity and sensitivity than acute
      phase proteins such as C-reactive protein.

PMID- 11587127
TI  - Serum apolipoprotein H and its relationship to blood pressure, serum lipids,
      fasting plasma glucose and insulin in normal individuals.
AB  - Apolipoprotein H (apo H), also known as beta2-glycoprotein 1, has recently become
      of interest in the field of haemostasis. As apo H is elevated in diabetes
      mellitus and dyslipidaemia, we wished to test the hypothesis that serum apo H
      concentration was related to fasting plasma glucose and insulin as well as blood
      pressure, body mass index, hip/waist ratio and serum lipids in normal
      individuals. Eighty-one healthy young individuals (46 females and 35 males) were
      studied. Their age was 20.7 +/- 0.75 years. Serum apo H significantly correlated
      with fasting plasma glucose (r = 0.24, P = 0.03) and serum LDL cholesterol (r =
      0.30, P = 0.006). In the females serum apo H significantly correlated with serum
      cholesterol concentration (r = 0.30, P = 0.04) and in males with serum HDL
      cholesterol concentration (r = 0.35, P = 0.04). In multifactorial regression
      analysis for serum apo H and the other variables for the 81 subjects, only gender
      and fasting plasma glucose remained statistically significant in the model. Serum
      apo H concentrations would be expected to increase by 21.7 mg/L for each single
      mmol/L increase in fasting plasma glucose (95% CI 2.3-41 2), P = 0.029, and to
      increase by 17.0 mg/L if the gender is male (95% Cl 0.7-332), P= 0.041.

PMID- 11587128
TI  - Measurement of asialylated LDL in the blood of patients with coronary artery
      disease by antibody-lectin sandwich assay.
AB  - Elevated concentrations of asialylated LDL (asialo-LDL) have been reported in
      patients with coronary artery disease (CAD). This may stimulate lipid
      accumulation in arterial intima cells and promote atherosclerosis. To investigate
      asialo-LDL as a potential risk-factor for coronary atherogenesis, we developed an
      antibody-lectin sandwich assay to measure levels in serum from CAD patients and
      age-matched control subjects. LDL was captured with an anti-apolipoprotein (apo)
      B antibody and asialylated oligosaccharides measured using the biotinylated D
      galactose (D-gal) binding lectin, Ricinus communis agglutinin 120 (RCA120), and a
      streptavidin-alkaline phosphatase conjugate. For the control and atherosclerotic
      subjects, median [interquartile range (IQR)] values for total concentrations of
      asialo-LDL were 240 mg,L (180-310 mg/L) and 220 mg/L (186-390 mg/L), respectively
      (P = 0.82). When expressed as a percentage of serum apo B-100, median (IQR)
      values were 18% (16-23%) and 19% (15-29%), respectively (P = 0.78). These results
      suggest asialo-LDL has little value as a risk factor for coronary
      atherosclerosis.

PMID- 11587129
TI  - Clinical evaluation of the ACS:180 cardiac troponin I assay.
AB  - All patients admitted to the coronary care unit with suspected acute coronary
      syndromes were evaluated by serial electrocardiography and blood draws on
      admission and at 4 and 12h from admission. Diagnosis was based on conventional
      WHO criteria. Samples were measured for creatine kinase (CK), cardiac troponin T
      (cTnT), myoglobin, CK isoenzyme MB (CK-MB) and cardiac troponin I (cTnI). A set
      of samples from individuals undergoing extreme endurance training was also
      examined. Analytical imprecision was consistent with published quality goals.
      Samples were stable for cTnI under a range of storage conditions, including
      multiple freeze thaw cycles. CK-MB, cTnI and cTnT were equally efficient for the
      diagnosis of acute myocardial infarction, irrespective of the final diagnostic
      criteria used. Both cTnI and cTnT were of equal efficiency in the identification
      of a high-risk subgroup of patients with unstable angina. Significant elevations
      of cTnI were not seen in an e ndurance-training group.

PMID- 11587131
TI  - Age- and gender-related changes in ligament components.
AB  - The age- and gender-related changes in extracellular matrix components (elastin,
      elastin cross-links, fibrillin, collagen and glycoprotein) and mineral components
      (calcium, Ca; phosphorus, P) in human lumbar yellow ligaments were investigated
      using samples obtained from surgical specimens. The mineral (Ca and P) contents
      increased with ageing (r = 0.703 and r = 0.772, respectively), whereas the
      contents of matrix components tended to decrease with ageing (elastin r = -0.261,
      elastin cross-links r = -0.213, fibrillin r = 0.494; collagen r = -0.322 and
      glycoprotein r = -0.143). Comparison of the male and female groups revealed that
      the ligament elastin content and elastin cross-links decreased in the male group,
      whereas the ligament collagen content decreased in the female group significantly
      in an age-dependent manner (r = -0.788, r = -0.753 and r = -0.721, respectively).
      These findings demonstrate age- and gender-related changes in mineral and matrix
      components (especially elastin and collagen) in the lumbar yellow ligaments in
      the Japanese population. It is suggested that elastin and collagen metabolism in
      ligaments changes both with age and according to gender.

PMID- 11587130
TI  - Biochemical investigation of foetal and neonatal thyroid function using the ACS
      180SE analyser: clinical application.
AB  - Despite sonographic detection of foetal goitre, uncertainty persists in the
      initial diagnosis of thyrotoxicosis and hypothyroidism. The aim of this study was
      to establish foetal and neonatal iodothyronine and thyrotrophin reference values
      for the ACS-180SE analyser. From 22 to 36 weeks of gestation, median foetal serum
      free thyroxine (FT4) levels increased from 6.0 pmol/L to 143 pmol/L, while free
      tri-iodothyronine (FT3) levels increased from 0.7 pmol/L to 1.9 pmol/L and mean
      thyrotrophin (TSH) levels remained stable (10.2 +/- 3.8mU/L; n = 33). At birth,
      concentrations were independent of gender and gestational age. Among the 10 cases
      of sonographically detected foetal goitre, serum TSH and FT4 were measured in
      five, showing hypothyroidism (3/5) or hyperthyroidism (2/5). Cord blood TSH
      levels reflected the efficacy of prenatal therapy. Measurement of foetal FT4 and
      TSH can be used to confirm foetal thyroid dysfunction, whereas treatment efficacy
      can be assessed sonographically and confirmed by measurement of TSH assay at
      birth.

PMID- 11587132
TI  - Bilirubin measured on a blood gas analyser: a suitable alternative for near
      patient assessment of neonatal jaundice?
AB  - The reliability of a recently released total bilirubin assay for a blood gas
      analyser was assessed in two Australian hospital laboratories. The instrument
      computes total bilirubin concentration from multi-wavelength absorbance
      measurements of undiluted whole blood or plasma. Performance of the Radiometer
      ABL 735 blood gas analyser bilirubin method (software version 3.6) was compared
      with a proven Roche diazo method for Hitachi analysers, calibrated using primary
      standards prepared from NIST SRM 916a bilirubin. Acceptable bilirubin results
      were found over a wide concentration range for most neonatal samples of whole
      blood or plasma. For adult specimens, bilirubin results were approximately 10%
      lower on the blood gas analyser. Within-run imprecision (whole blood) was < 2.5%,
      between-day imprecision (synthetic controls) < 1.0%, and the bilirubin assay for
      both whole blood and plasma was linear to 1,000 micromol/L. Using sampling
      options from 35 microL to 195 microL, bilirubin results differed by less than 3%,
      with a 95 microL syringe option producing the highest results. We conclude that
      the Radiometer ABL 735 bilirubin assay is suitable for near-patient assessment of
      neonatal jaundice using whole blood, thus eliminating the need for sample
      centrifugation. Verification using laboratory methods can be used when required.
      A positive correction of approximately 10% is required for adult specimens to
      conform with Hitachi results (SRM 916a calibration), possibly due to the optical
      characteristics of the higher proportion of conjugated bilirubin and other
      substances present in most adult samples.

PMID- 11587133
TI  - Application of solid-phase micro-extraction technology to drug screening and
      identification.
AB  - Benzodiazepines, tricyclic antidepressants and local anaesthetics are frequently
      involved in poisoning episodes and fatalities. A specific, sensitive and rapid
      procedure for identifying and quantifying such drugs in postmortem matrices has
      been developed using solid-phase micro-extraction (SPME) and gas chromatography
      mass spectrometry. Very clean extracts were obtained in one step using SPME. The
      most commonly used fibre coatings were tested to select the best coating for SPME
      of the drugs. The appropriate fibre coating for most drugs was polyacrylate,
      followed by Carbowax-divinylbenzene. A Hewlett-Packard 5890 gas chromatograph in
      combination with a Trio 2000 mass spectrometer was used to analyse the samples.
      Temperature, time, pH and addition of sodium chLoride were optimized to obtain
      consistent extraction. The between-day and within-day coefficients of variation
      were less than 16% and less than 6%, respectively.

PMID- 11587134
TI  - Phylogenic study of denaturation of lactate dehydrogenase isoenzymes from
      different species by high and low temperature.
AB  - We studied the influence of storage at different temperatures on lactate
      dehydrogenase (EC 1.1.1.27; LD) isoenzymes from different tissues and different
      species, and analysed biochemical and biophysical mechanisms of denaturation
      during storage. Isoenzymes obtained from tissue extracts of mammals, poultry,
      reptiles. amphibians and fish were shown to have their own denaturation ranges at
      low temperatures by post-treatment assays and transition temperature analysis.
      These ranges were between -10 and -20 degrees C for most vertebrate LD
      isoenzymes. Circular dichroism analysis indicated that the denaturation of LD
      isoenzymes was probably caused by a change in the hydrophobic interactions in the
      molecule. At higher temperatures, LD-1 isoenzyme was more thermostable than LD-5
      from the same animal species, except for rats, the LD-5 activity of which was
      more thermostable than the LD-1 activity. These findings indicate that variable
      effects of storage of samples and reference materials at low temperatures should
      be considered, and that it is necessary to establish LD isoenzyme standards for
      animal clinical laboratory investigations.

PMID- 11587135
TI  - Measurement of pyruvate in blood by high-performance liquid chromatography with
      fluorescence detection.
AB  - Accurate measurement of pyruvate is particularly important in the detection of
      mitochondrial enzyme disorders. describe a simple high-performance liquid
      chromatography assay for pyruvate with derivatization and fluorescence detection.
      Between-run variation is below 4.5% and the method is linear between I and 1,200
      micromol/L. The mean recovery is 101%. After sample pretreatment, the calculated
      pyruvate concentration proved to be stable for 15 days when samples were kept at 
      20 degrees C.

PMID- 11587136
TI  - Positive screening tests for barbiturates in urine samples in the York area over
      a 1-year period.
AB  - Following the screening of urine samples for a panel of drugs over a period of 1
      year, a peak was observed during December 1999 and January 2000 in the numbers of
      samples testing positive for both morphine and barbiturates. This increase may be
      due to the adulteration of street heroin with barbiturate during this period.

PMID- 11587137
TI  - Immulite 2000 parathyroid hormone assay: stability of parathyroid hormone in EDTA
      blood kept at room temperature for 48 h.
AB  - Parathyroid hormone (PTH) concentrations were compared in serum and EDTA plasma
      from 36 patients attending a renal stone clinic. Serum PTH concentrations ranged
      from 0.9 to 10.9 pmol/L, with a mean of 4.6pmol/L. When serum and EDTA plasma
      results were compared, in samples frozen within 30 min of collection, EDTA plasma
      results were found to be significantly higher than those in serum (P < 0.0001;
      Wilcoxon test), with an average increase of 19.5% over the serum result. Results
      from EDTA-preserved blood left to stand at room temperature for 48 h were on
      average 14.8% lower than results from the corresponding EDTA plasma samples
      frozen within 30 min, with highly significant difference (P < 0.0001). Freshly
      frozen serum and 48h EDTA plasma PTH results were not significantly different.
      Parathyroid hormone in EDTA-preserved blood is not completely stable, and this
      could lead to misclassification of results for samples which are not frozen
      quickly.

PMID- 11587138
TI  - IgD myeloma: a potential missed diagnosis.
AB  - This report describes a case of IgD lambda myeloma which was discovered only
      following investigation of a suspicious 'low gamma region'. If anti-IgD
      investigations had not been carried out, it may have been misinterpreted as Bence
      Jones myeloma. The case illustrates that evaluation of serum and urine in cases
      of suspected myeloma is mandatory and that the possibility of IgD myeloma in
      cases that appear to be 'free light chain' paraproteins only should be
      investigated.

PMID- 11587139
TI  - Autoimmune hypothyroidism coexisting with a pituitary adenoma secreting thyroid
      stimulating hormone, prolactin and alpha-subunit.
AB  - A 44-year-old woman presented to her GP with excessive tiredness. She had
      positive thyroid microsomal and thyroglobulin autoantibodies and was found to
      have an elevated serum thyroid-stimulating hormone (TSH) concentration of 8.37
      (normal = 0.15-3.5)mU/L and a low normal total thyroxine (T4) of 86 (reference
      range 60-145)nmol/L. She was rendered symptom free on a dose of 150 microg of
      thyroxine per day. However, her TSH failed to return to normal, and following a
      further increase in her thyroxine dose she was referred to the endocrine clinic
      for further assessment. Her TSH at this stage was 14mU/L, free T4 (fT4) 28
      (normal = 10-27)pmol/L and free T3 (fF3) 10 (normal = 4.3-7.6)pmol/L. She denied
      any problems with adherence to her medication. Her serum prolactin was elevated
      at 861 (normal = 60-390)mU/L. A pituitary tumour was suspected and an MRI scan
      showed a macroadenoma of the right lobe of the pituitary, extending into the
      suprasellar cistern. The tumour was resected trans-sphenoidally. Electron
      microscopy showed a dual population of neoplastic cells compatible with a
      thyrotroph cell and prolactin-secreting adenoma. Immunocytochemistry and cell
      culture studies confirmed the secretion of TSH, prolactin and alpha-subunit.
      Postoperative combined anterior pituitary function tests did not demonstrate any
      deficiency of anterior pituitary hormones. A repeat MRI scan showed no
      significant residual tumour; however, her serum TSH and prolactin levels remained
      high and she was given a course of pituitary irradiation. This case illustrates
      the difficulty of diagnosing a TSHoma when it coexists with autoimmune
      hypothyroidism. We believe the combination of pathologies reported here is
      unique.

PMID- 11587140
TI  - Clinical limitation of bone-specific alkaline phosphatase assays.

PMID- 11587141
TI  - Correction to 'improved immunoturbidimetric assay for cystatin C'.

PMID- 11587142
TI  - Are natriuretic peptides clinically useful as markers of heart failure?

PMID- 11587143
TI  - Dry eye disease: the scale of the problem.
AB  - Dry eye disease, or keratoconjunctivitis sicca, is among the most frequently
      established diagnoses in ophthalmology; in Germany, one in four patients
      consulting an ophthalmologist complains of the symptoms of dry eye. Although
      epidemiological studies investigating the prevalence of dry eye disease are rare,
      published studies indicate that up to 20% of adults aged 45 years or more
      experience dry eye symptoms. Recent studies have shown that immunologic changes
      play a role in the pathogenesis of dry eye, not only in Sjogren's syndrome, but
      also in postinfectious and age-related conditions. Despite increasing
      understanding of the pathogenic factors involved in dry eye disease, there has
      been a lack of consensus on diagnostic criteria, classification of disease
      states, and the aims and interpretation of specific diagnostic tests. There is a
      need, therefore, for standardization of disease terminology and diagnostic tests
      in order to improve the usefulness of epidemiological and clinical investigation
      of this important ocular disorder.

PMID- 11587144
TI  - The ocular surface and tear film and their dysfunction in dry eye disease.
AB  - The ocular surface, tear film, lacrimal glands, and eyelids act as a functional
      unit to preserve the quality of the refractive surface of the eye and to resist
      injury and protect the eye against changing bodily and environmental conditions.
      Events that disturb the homeostasis of this functional unit can result in a
      vicious cycle of ocular surface disease. The tear film is the most dynamic
      structure of the functional unit, and its production and turnover is essential to
      maintaining the health of the ocular surface. Classically, the tear film is
      reported to be composed of three layers: the mucin, aqueous, and lipid layers.
      The boundaries and real thickness of such layers is still under discussion. A
      dysfunction of any of these layers can result in dry eye disease.

PMID- 11587145
TI  - The pathology of dry eye.
AB  - Homeostasis of the tear film involves delicate hormonal and neuronal regulatory
      mechanisms. The eye appears to be a target organ for sex hormones, particularly
      the androgens, as they modulate the immune system and trophic functions of the
      lacrimal glands and the functioning of the meibomian glands. The cornea, lacrimal
      glands, mucous cells, and meibomian glands are all richly innervated, indicating
      the importance of nervous regulation in their function. Parasympathetic,
      sympathetic, and sensory innervation play complex stimulatory or inhibitory
      roles, and neuronal pathways interact via complex surface results cascades.
      Abnormalities at any point in these pathways can cause overall dysregulation of
      lacrimal function. Whatever the initial causes of dry eye, chronic dryness of the
      ocular surface results in inflammatory reactions and gradual destruction of the
      lacrimal glands and conjunctival epithelium. Once dry eye disease has developed,
      inflammation is the key mechanism of ocular surface injury, as both the cause and
      consequence of cell damage. In practice, dry eye can be associated with Sjogren's
      syndrome, allergies, infection, blepharitis, and preservative-containing eye
      drops.

PMID- 11587146
TI  - Diagnosis of dry eye.
AB  - Dry eve disease is characterized by symptoms, ocular surface damage, reduced tear
      film stability, and tear hyperosmolarity. There are also inflammatory components.
      These features can be identified by various kinds of diagnostic tests (symptom
      questionnaires, ocular surface staining, tear break-up time, and osmometry),
      although there may not be a direct correlation between the number or severity of
      symptoms and the degree of ocular surface damage or tear deficiency. Once the
      diagnosis of dry eye disease has been established, further tests can be used to
      classify the condition into tear-deficient or evaporative dry eve. The two forms
      of dry eye are not mutually exclusive and often co-exist. The optimal diagnosis
      of dry eye disease, therefore, depends on the results of several tests, and this
      article suggests an appropriate order for performing these tests at a single
      clinic visit.

PMID- 11587147
TI  - The treatment of dry eye.
AB  - The most widely used therapy for dry eye disease is tear replacement by topical
      artificial tears. Punctal occlusion to prevent the drainage of natural or
      artificial tears is the most common non-pharmacological treatment. These and
      other traditional therapies for dry eye disease are only palliative, however, as
      they replace or conserve the tears without necessarily correcting the underlying
      disease process. As our understanding of the pathology of dry eye disease
      improves, new treatment strategies are being developed. Topical anti-inflammatory
      and immunomodulatory agents, such as cyclosporin A, are under investigation in
      the treatment of dry eye, as it is anticipated that they will correct the vicious
      cycle of inflammation and cell damage on the ocular surface and lacrimal glands.

PMID- 11587148
TI  - Laragh's lessons in pathophysiology and clinical pearls for treating
      hypertension.

PMID- 11587149
TI  - Evaluation of white coat hypertension in children: importance of the definitions
      of normal ambulatory blood pressure and the severity of casual hypertension.
AB  - To better describe the phenomenon of white coat hypertension (WCH) in children,
      we reviewed our single-center experience using ambulatory blood pressure
      monitoring to determine: 1) how the choice of threshold limits for defining
      ambulatory hypertension affects the determination of WCH, and 2) whether the
      severity of casual hypertension predicts the occurrence of WCH. Using the same
      daytime ambulatory blood pressure (ABP) data from 71 children (age 11.9 3.4
      years) with persistently elevated casual blood pressure (BP), the prevalence of
      WCH was compared using 95th percentile BP limits from the Task Force on High
      Blood Pressure in Children (TF) and from normative pediatric daytime ambulatory
      BP (ABP) data. To quantify casual hypertension severity, average clinic BP was
      divided by the patient-specific TF 95th percentile BP to generate a BP index (ie,
      BP index of 1.1=10% above 95th percentile). The WCH prevalence was lower by
      normative ABP criteria than by TF criteria (31% v 59%, P < .001), but did not
      vary significantly by age, gender, race, or body mass index. Logistic regression
      showed that higher systolic BP index (P < .001) or diastolic BP index (P < .01)
      was associated with a lower probability of WCH. Specifically, as systolic BP
      index increased from 1.0 to 1.2, the estimated probability of WCH decreased from
      87% to 15%, respectively. These data suggest that the use of the lower TF limits,
      derived solely from resting BP measurements, may overestimate WCH prevalence in
      ambulatory children. In addition, these data confirm in children the finding in
      adults that WCH is highly prevalent when casual hypertension is borderline or
      mild, but uncommon when moderate or severe.

PMID- 11587151
TI  - Vascular cell adhesion molecule-1 as a biochemical marker of left ventricular
      mass in the patients with hypertension.
AB  - Plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular
      adhesion molecule-1 (sVCAM-1), and E-selectin were measured in 80 outpatients
      with uncomplicated essential hypertension. Although the levels of E-selectin and
      sICAM-1 were similar between the patients with and without left ventricular (LV)
      hypertrophy, sVCAM-1 level was significantly elevated in the patients with LV
      hypertrophy (759.7+/-154.6 ng/mL nu 984.4+/-240.6 ng/mL, P < .0001). The LV mass
      normalized to body surface area or height were significantly correlated with
      sVCAM-1 (r=0.615, P < .0001 and r=0.571, P < .0001, respectively). These results
      indicate that a soluble adhesion molecule is correlated with LV mass in
      uncomplicated essential hypertensive patients.

PMID- 11587150
TI  - Endothelial dysfunction in resistance arteries is related to high blood pressure
      and circulating low density lipoproteins in previously treated hypertension.
AB  - BACKGROUND: Peripheral endothelial dysfunction has been demonstrated in
      hypertension. However, its relationship to blood pressure (BP) load, vascular
      structure, and metabolic disturbances in patients with long-standing, previously
      treated hypertension is unclear. METHODS: A total of 41 patients with stage I to
      III essential hypertension and electrocardiographic left ventricular hypertrophy
      were studied. After 2 to 3 weeks of placebo treatment we measured nitroprusside
      induced relaxation (NIR), acetylcholine-induced relaxation (AIR), and media:lumen
      ratio in isolated, subcutaneous resistance arteries by myography, as well as 24-h
      ambulatory BP, and serum lipids. RESULTS: Maximal AIR correlated negatively with
      median 24-h diastolic BP (r=-0.42, P=.01), and sensitivity to AIR correlated
      negatively with serum low density lipoprotein (LDL) (r =-0.36, P < .05). In
      multiple regression analyses, sensitivity to AIR correlated negatively with serum
      LDL (beta=-0.33) independently of maximal NIR (beta=0.41) (adjusted R2 =0.26, P <
      .01). Maximal acetylcholine-induced relaxation correlated negatively with median
      24-h diastolic BP (beta=-0.38) independently of maximal NIR (beta=0.45) (adjusted
      R2= 0.32, P < .001). Acetylcholine-induced relaxation was not significantly
      related to diabetes or to media:lumen ratio (r = -0.26, NS). CONCLUSIONS: High
      diastolic BP and high serum LDL were associated with impaired maximal AIR and
      reduced sensitivity to AIR, respectively, independently of smooth muscle cell
      responsiveness to nitroprusside. This indicated decreasing endothelial function
      in small resistance arteries with increasing BP and increasing LDL in
      hypertension. Endothelial function was not significantly related to vascular
      structure of the resistance arteries or to diabetes in these patients with long
      standing hypertension.

PMID- 11587152
TI  - Influence of lead on rat thoracic aorta contraction and relaxation.
AB  - Low levels of lead, but not high levels, produce hypertension. This mystery has
      not yet been resolved. In this study we compared the in vitro vasoresponsiveness
      in rat thoracic aorta to low dose (10(-8) mol/L) and high dose (10(-5) mol/L and
      10(-4) mol/L) lead acetate. In addition to the direct response to lead, we
      examined reactivity to norepinephrine, acetylcholine, isoproterenol, phorbol
      ester, and calcium in the presence and absence of lead. Neither low-dose nor high
      dose lead directly affected aortic contractile or relaxant responses. However,
      lead, only at the highest concentration (10(-4) mol/L), increased the
      contractions to calcium at all submaximal calcium concentrations. We conclude
      that low-dose lead must increase blood pressure indirectly through a humoral
      effect. The reasons for the failure of high-dose lead to influence blood pressure
      remain to be explored.

PMID- 11587153
TI  - Elevated potassium intake inhibits neointimal proliferation in the swine coronary
      artery.
AB  - BACKGROUND: Previously, we reported that elevated extracellular potassium
      concentration in vitro inhibited proliferation and migration of vascular smooth
      muscle cells, formation of free radical compounds by macrophages, and reduced
      platelet sensitivity to agonists. More recently, we described a reduction in
      neointimal proliferation after balloon angioplasty injury in the carotid arteries
      of rats associated with an elevation of dietary potassium intake during a 4-week
      experiment. In the present study we conducted a similar investigation in the
      swine coronary artery balloon angioplasty model. PROCEDURES: Two groups of seven
      castrated male swine were studied; for 28 days the normal potassium group
      consumed a diet containing 0.25% potassium and the high potassium group ate diet
      containing 2.0% potassium. After 14 days on the diet, balloon angioplasty was
      performed. After an additional 14 days on the same diets the hearts were removed,
      and normal and lesioned sections of the artery were analyzed histologically.
      RESULTS: The neointimal area was markedly less in the high potassium group than
      in the normal potassium group, 0.33+/-0.04 mm2 v 0.74+/-0.10 mm2 (P < .004).
      Neointimal area-to-total wall area ratio in the normal potassium group averaged
      0.199+/-0.018, significantly greater than the ratio computed for the elevated
      potassium group, 0.120+/-0.015 (P < .006). CONCLUSION: These results support the
      hypothesis that a high level of dietary potassium intake inhibits neointimal
      proliferation after balloon angioplasty in the swine coronary artery.

PMID- 11587154
TI  - Sleep quality and blood pressure dipping in obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with poor sleep quality
      and a high incidence of nondipping. The aim of this study was to determine the
      association of sleep quality and nocturnal blood pressure (BP) dipping in an OSA
      population. METHODS: A total of 44 untreated subjects with mild to severe OSA
      underwent overnight-attended polysomnography and 24-h ambulatory BP monitoring.
      Subjects were off antihypertensive medication. The percentage of slow wave sleep,
      percentage of time awake after sleep onset during the sleep period, sleep
      efficiency, and arousal index were chosen as measurements of sleep quality.
      Dipping was evaluated using the change in systolic BP, diastolic BP, and mean
      arterial pressure. Patients were classified as dippers and nondippers based on a
      nocturnal drop in mean arterial pressure > 10%. Differences between groups were
      evaluated by independent sample t tests. Pearson correlation and linear
      regression were used to evaluate the association of sleep quality and dipping.
      RESULTS: There were no differences between dippers and nondippers with regard to
      body mass index, age, or respiratory disturbance index. A total of 84% were
      nondippers. No difference was found between dippers and nondippers in sleep
      quality. None of the sleep quality measures correlated with the measurements of
      dipping. In multiple regression analyses, the percentage of slow wave sleep and
      arousal index each independently predicted only a small percentage of the
      variance (approximately 10%) of nocturnal DBP dipping. CONCLUSIONS: The
      prevalence of nondipping was very high in a population of untreated patients with
      mild to severe OSA. Nonetheless, sleep quality did not appear to be related to BP
      dipping.

PMID- 11587155
TI  - Role of gender on renal interstitial hydrostatic pressure and sodium excretion in
      rats.
AB  - The objective of this study was to compare renal interstitial hydrostatic
      pressure (RIHP) and sodium excretion in female and male Sprague-Dawley (SD) rats.
      The RIHP and pressure natriuresis responses were determined in female (n=13) and
      male (n=8) SD rats. Renal perfusion pressure (RPP) was controlled at two levels
      (100 and 120 mm Hg). Clearances were taken at each level and RIHP was measured
      with a chronically implanted polyethylene matrix in all rats. At the lower RPP
      level, RIHP was similar in both groups of rats (5.2+/-0.2 mm Hg for female, and
      5.5+/-0.4 mm Hg for male), whereas fractional excretion of sodium (FENa) was
      significantly lower (P < .05) in male (1.10+/-0.27%) as compared to female
      (2.23+/-0.32%) rats at similar lower RPP. Allowing RPP to increase from 100 to
      120 mm Hg resulted in similar increases in FENa (deltaFENa), urine flow rate
      (deltaV), and RIHP (deltaRIHP) in both groups of rats. The deltaFENa, deltaV, and
      deltaRIHP were 1.67+/-0.43%, 38.45+/-4.74 microL/min/g kidney weight, and 2.7+/
      0.2 mm Hg for female, and 1.79+/-0.42%, 30.40+/-4.37 microl/min/g kidney weight,
      and 2.8+/-0.3 mm Hg for male rats. In conclusion, RIHP is similar in female and
      male SD rats at similar RPP levels. Both female and male SD rats increase RIHP
      and sodium excretion similarly in response to increases in RPP. The lower basal
      FENa in male as compared to female rats may play an important role in the more
      significant elevation of blood pressure in males with age.

PMID- 11587156
TI  - Differences in K+ current components in mesenteric artery myocytes from WKY and
      SHR.
AB  - Previous studies have documented increased K+ permeability of arterial smooth
      muscle in hypertension and suggested a role in altered arterial contractile
      function. To characterize the mechanisms responsible for these alterations, we
      determined the contribution of K+ current (IK) components to whole cell IK in
      freshly dispersed myocytes and tetraethylammonium (TEA)-induced contractile
      responses in mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously
      hypertensive rats (SHR). Tetraethylammonium produced a larger tonic contractile
      response in SHR with a lower threshold compared to WKY (ie, 0.1 v 1 mmol/L),
      which was due in part to the larger Ca2+ current in SHR. Whole cell IK recorded
      by perforated patch methods was similar at a holding potential (HP) of -60 mV
      (IK60), but were larger in SHR when recorded from a HP of -20 mV (IK20). The
      selective blocker iberiotoxin (IbTX) was used to separate the contribution of
      voltage- (Kv) and calcium-dependent (KCa) components of IK60. The IK60 and IK20
      component inhibited by 100 nmol/L IbTX (ie, KCa) was larger in SHR than in WKY
      myocytes, whereas the IbTX-insensitive IK60 component (ie, Kv) was larger in WKY.
      In the presence of IbTX, 1 and 10 mmol/L TEA inhibited a larger fraction of IK60
      in SHR myocytes compared with WKY. The activation properties of the TEA-sensitive
      and TEA-insensitive Kv components determined by fitting a Boltzmann activation
      function to the current-voltage data, exhibited both group and treatment
      differences in the half maximal activation voltage (V0.5). The V0.5 of the TEA
      sensitive Kv component was more positive than that of the TEA-insensitive
      component in both groups, and values for the V0.5 of both TEA-sensitive and TEA
      insensitive components were more negative in SHR than WKY. These results show
      that SHR myocytes have larger KCa and smaller Kv current components compared with
      WKY. Furthermore, SHR myocytes have a larger TEA-sensitive Kv component. These
      differences may contribute to the differences in TEA contractions, resting
      membrane potential, Ca2+ influx, and KCa current reported in hypertensive
      arteries.

PMID- 11587157
TI  - Doxazosin reduces prevalence of small dense low density lipoprotein and remnant
      like particle cholesterol levels in nondiabetic and diabetic hypertensive
      patients.
AB  - Small dense low density lipoprotein (LDL) and remnant lipoproteins are potent
      atherogenic lipoproteins, often elevated in the plasma of patients with type 2
      diabetes. The alpha1-blocker doxazosin has been reported to favorably affect the
      plasma lipid profile. We examined whether doxazosin could reduce these
      atherogenic lipoproteins in hypertensive subjects with and those without type 2
      diabetes. Seventeen nondiabetic hypertensive patients and 33 hypertensive
      patients with type 2 diabetes were studied. Doxazosin (2 to 4 mg) was
      administered alone or with other previously received antihypertensive drugs for 6
      months. Mean LDL size was measured by 2% approximately 16% gradient gel
      electrophoresis. Remnant-like particle (RLP)-cholesterol was measured with the
      use of an affinity column containing anti-apoA1 and B100 monoclonal antibodies.
      Doxazosin effectively decreased blood pressure (BP) without significantly
      affecting glucose, glycosylated hemoglobin (HbA1c), or C-peptide levels in both
      nondiabetic and diabetic patients. Doxazosin significantly reduced triglyceride,
      apo CIII, and apo B, but did not alter total-, LDL- or HDL-cholesterol. Mean LDL
      particle diameter was significantly increased from 25.6+/-0.6 nm to 25.9+/-0.4 nm
      (P < .001) by doxazosin treatment, regardless of the presence of diabetes.
      Consequently, the prevalence of small dense LDL (<25.5 nm) was halved in both
      groups. The increase in LDL size significantly correlated with decrease in
      triglyceride level (r=-0.798, P < .0001). Doxazosin significantly reduced RLP
      cholesterol in both groups. These results suggest that doxazosin may help to
      prevent coronary artery disease by reducing atherogenic lipoproteins, including
      small dense LDL and remnant lipoproteins, in hypertensive patients, regardless of
      the presence of diabetes.

PMID- 11587158
TI  - Interaction between sodium intake, angiotensin II, and blood pressure as a cause
      of cardiac hypertrophy.
AB  - Cardiac hypertrophy is common in hypertension but its development is influenced
      by angiotensin II, sodium intake aldosterone, and the time of day blood pressure
      (BP) is elevated. This study examined and compared cardiac hypertrophy in the 2
      kidney-1 clip (2K-1C) and 1 kidney-clip (1K-1C) Goldblatt models of hypertension.
      Blood pressure was measured by telemetry in a selected group of rats. Rats were
      placed on a high (4%) or reduced (0.2%) salt intake and were given captopril (75
      mg/kg per day) or losartan (10 mg/kg per day). Appropriate sham-operated and
      untreated controls were used. Cardiac hypertrophy was greater in the IK-1C than
      in the 2K-1C model. Day and sleep BP were also higher. In the 2K-1C model BP was
      lower on the reduced salt intake and BP decreased with captopril in both reduced
      and high salt groups. Cardiac weight and index decreased significantly only in
      the reduced salt and captopril group and was less than the size before treatment.
      In the 1K-1C model captopril caused all BP measures to decrease in the reduced
      salt group but had no significant effect in the high salt group. Cardiac weight
      and index were reduced only in the reduced salt + captopril group and cardiac
      weight was less than the pretreatment control. Losartan had a similar effect in
      the lK-1C model to that achieved with captopril. The responses achieved
      correlated in part with renin status and dependency level. There is no prime
      determinant of cardiac hypertrophy. Blood pressure, sodium intake, and hormonal
      status are all important. It is postulated that the common pathway may be
      alterations in cell composition that signal the nucleus to increase cell growth.

PMID- 11587159
TI  - Differential effects of ACE-inhibition and angiotensin II antagonism on
      fibrinolysis and insulin sensitivity in hypertensive postmenopausal women.
AB  - The aim of this study was to compare the effects of trandolapril and losartan on
      plasminogen activator inhibitor type 1 (PAI-1) levels and insulin sensitivity in
      hypertensive postmenopausal women. We studied 89 hypertensive (diastolic blood
      pressure >90 and <110 mm Hg) postmenopausal women, aged 51 to 60 years not taking
      any hormone replacement therapy. Diabetic, obese, and smoking patients were
      excluded. After a 4-week placebo period, they were randomized to receive 2 mg of
      oral trandolapril (n=45) or 50 mg of oral losartan (n=44) for 12 weeks according
      to a double-blind, parallel group design. At the end of the placebo and active
      treatment periods, blood pressure (BP) was measured, plasma samples were drawn to
      evaluate PAI-1 antigen levels, and insulin sensitivity was assessed. Both
      trandolapril and losartan reduced systolic BP (by a mean of 16.9 mm Hg and 15.2
      mm Hg, respectively, P < .01 v placebo) and diastolic BP (by a mean of 13.1 mm Hg
      and 11.9 mm Hg, respectively, P < .01 v placebo) with no difference between the
      two treatments. The PAI-1 antigen levels were significantly decreased by
      trandolapril (from 36.9+/-21 ng/dL to 27.2+/-17 ng/dL, P < .05), but not by
      losartan (from 35.3+/-22 ng/dL to 37.1+/-23 ng/dL, P=not significant). Glucose
      infusion rate was significantly increased by trandolapril (from 6.67+/-0.56
      mg/min/kg to 7.9+/-0.65 mg/min/kg, P < .05), but was not significantly modified
      by losartan (from 6.7+/-0.47 mg/min/kg to 6.9+/-0.50 mg/min/kg, P= not
      significant). In the trandolapril group the PAI-1 decrease correlated with
      glucose infusion rate increase (r=0.36, P=.045) These results provide evidence of
      different effects of angiotensin converting enzyme inhibitors and AT1 antagonists
      on fibrinolysis and suggest that the PAI-1 decrease induced by angiotensin
      converting enzyme inhibitors is related to their action on insulin sensitivity
      and is not dependent on angiotensin II antagonism but rather on other mechanisms.
      It remains to be seen whether these findings apply to other patient populations
      than postmenopausal women.

PMID- 11587160
TI  - Rapid fusion of granules with neutrophil cell membranes in hypertensive patients
      may increase vascular damage.
AB  - In essential hypertension (EHT) the presence of a metabolic syndrome increases
      the risk of cardiovascular disease. A cell membrane abnormality is implicated but
      its role in cardiovascular disease is unclear. Neutrophil accumulation, which
      occurs by beta2-integrin (CD11b/CD18) expression, followed by release of
      proinflammatory factors from primary vesicles is an important factor in vascular
      damage. CD11b and CD69 expression on neutrophils from normal controls and EHT
      patients was determined by fluorescence-activated cell scanning. Neutrophils were
      activated with phorbol myristate acetate (PMA). Protein kinase C (PKC) and
      calpain were inhibited with bisindolylmaleimide and E64d, respectively. In EHT
      patients CD11b was not increased on neutrophils at rest. However, EHT neutrophils
      more readily expressed CD11b on incubation in phosphate-buffered saline and more
      cells went on to exocytose primary granules indicated by expression of CD69.
      Stimulation with PMA caused more rapid activation in EHT neutrophils with
      expression of CD11b, followed rapidly by exocytosis of primary granules.
      Bisindolylmaleimide slowed but did not prevent CD11b expression, which, together
      with primary granule exocytosis, continued to be faster in EHT neutrophils. E64d
      also slowed but did not prevent either CD11b expression or primary granule
      exocytosis, but this inhibitor did abolish the difference between NC and EHT
      neutrophils. The membrane abnormality in EHT may contribute to cardiovascular
      risk by increasing the rate of vesicle fusion with the cell membrane to increase
      neutrophil accumulation and release of inflammatory agents at sites of vascular
      damage. Calpain activation may be the rate-limiting component that is abnormal.

PMID- 11587161
TI  - -344C/T polymorphism of CYP11B2 gene in Italian patients with idiopathic low
      renin hypertension.
AB  - Most patients with low renin essential hypertension are not qualitatively
      different from patients with idiopathic hyperaldosteronism, as in both conditions
      aldosterone secretion is not appropriately reduced. The aim of the study was to
      investigate allele and genotype frequencies of the -344C/T polymorphism, located
      in the promoter region of the aldosterone synthase gene, in 83 patients with
      idiopathic low renin hypertension characterized by an increased aldosterone to
      renin ratio, including both patients with low renin essential hypertension (n=53)
      and subjects with idiopathic hyperaldosteronism (n=30), compared with 78 patients
      with normal to high renin essential hypertension and 126 normotensive control
      subjects. The relationship of -344C/T genotypes to basal and postcaptopril plasma
      aldosterone/plasma renin activity ratio was also examined in the entire
      hypertensive population. An increased frequency of the T allele and a relative
      excess of TT homozygosity over CC homozygosity were found in patients with
      idiopathic low renin hypertension in comparison with both normal to high renin
      hypertensives and normotensive controls. A higher post-captopril aldosterone to
      renin ratio was found in the hypertensives with TT genotype than in those with CC
      genotype, and TT+TC genotypes were associated with a smaller decrease in the
      aldosterone-to-renin ratio elicited by captopril administration. The present
      study suggests that the -344C/T polymorphism, or a functional variant in linkage
      disequilibrium with it, may play a role in the abnormal regulation of aldosterone
      secretion in idiopathic low renin hypertension.

PMID- 11587162
TI  - Impact of smoking cessation on ambulatory blood pressure and heart rate in
      postmenopausal women.
AB  - BACKGROUND: Smoking and hypertension interact to increase the incidence of
      cardiovascular disease; however, little is known about the effects of smoking
      cessation on blood pressure (BP) control. We prospectively evaluated the impact
      of smoking cessation on clinic and ambulatory BP and heart rate (HR) in stage 1
      hypertensive and normotensive postmenopausal women. METHODS: A total of 66 women
      were randomly assigned using a 3:1 randomization scheme to immediate smoking
      cessation or to a wait list control group. Clinic and ambulatory BP and HR, and
      24-h urinary catecholamine concentrations were obtained at baseline and again at
      6 weeks. Carbon monoxide levels and self-report were used to assess compliance
      with smoking cessation. RESULTS: Ambulatory monitoring showed that the awake SBP
      decreased by 3.6+/-1.9 mm Hg in the treated subjects who quit smoking (n=19),
      whereas in the control group (n=15) there was an increase of 1.7+/-2.4 mm Hg
      (P=.045). Awake HR decreased after smoking cessation by 7+/-1 beats/min and did
      not change (0+/-1 beat/min) in the control group (P=.001). Blood pressure and HR
      did not significantly change during sleep after smoking cessation. Changes in the
      awake HR correlated with changes in urinary epinephrine concentrations (r= 0.58,
      P=.001), and norepinephrine concentrations (r= 0.45, P=.001), There was no
      significant change in clinic systolic BP, diastolic BP, or HR between groups.
      CONCLUSIONS: Smoking cessation reduces systolic BP and HR during the daytime,
      when patients typically smoke. These hemodynamic changes are due in part to
      reductions in sympathetic nervous system activity.

PMID- 11587163
TI  - Hypertension treatment patterns in American Indians: the strong heart study.
AB  - Pharmacologic treatment patterns for hypertensive American Indians from 13
      communities in Arizona, Oklahoma, South Dakota, and North Dakota were assessed.
      Participants (2254 women and 1384 men, aged 48 to 79 years) completed a clinical
      examination between July 1993 and December 1995. The mean of two blood pressure
      (BP) measurements and detailed medication histories were obtained. The observed
      prevalence of hypertension was 46.7% (n=1698). In participants taking
      antihypertensive medications (n=1114), four principal drug classes were
      evaluated: diuretics, calcium channel blocking agents, beta-blocking agents, and
      angiotensin-converting enzyme (ACE) inhibitors. Among treated hypertensive
      participants, 71.4%, 24.6%, and 4.0% received one, two, and three medications,
      respectively. Among single drug regimens, ACE inhibitors (n=340) were used most
      often (49.4%), with calcium channel blocking agents and diuretics accounting for
      24.2% and 19.9%, respectively. Although multiple drug class therapies varied, the
      combination of a diuretic and ACE inhibitor (n=120) accounted for 47.4% of dual
      therapy use. Hypertension control (SBP < 140 mm Hg, DBP < 90 mm Hg) rates were
      highest for those on dual therapies (65.4%), followed by participants on single
      (53.8%) and triple (43.6%) therapies. Among monotherapies, diuretics exhibited
      the best overall hypertension control rate in both diabetics (63.0%) and
      nondiabetics (68.0%), versus 47% to 61% for other remaining agents. The frequent
      use of ACE inhibitors, used singly or in combination, reflects the high
      prevalence of diabetes among American Indians. ACE inhibitors, combined with
      diuretics, were particularly useful in achieving BP control in this population.

PMID- 11587164
TI  - Changes in the phamacologic treatment of hypertension in the Department of
      Veterans Affairs 1997-1999: decreased use of calcium antagonists and increased
      use of beta-blockers and thiazide diuretics.
AB  - Older studies of antihypertensive treatment have shown that prescribing patterns
      are not consistent with recommendations from expert national panels. We
      determined whether prescribing patterns for antihypertensive drugs changed
      recently in the largest integrated health care system in the United States.
      Specifically, we determine 1) patterns of antihypertensive medication use at all
      Department of Veterans Affairs (VA) medical facilities for fiscal years 1997 to
      1999, 2) the cost of this care, and 3) savings associated with changes in
      treatment patterns. Data were aggregated by individual medication as well as by
      antihypertensive drug class. Estimates of VA national antihypertensive drug costs
      are based on the median cost and the number of units for each dosage form of each
      medication dispensed at all facilities. At VA medical facilities, calcium
      antagonist use went from 33% to 29.3% of antihypertensive treatment days between
      1997 and 1999, angiotensin converting enzyme (ACE) inhibitor/angiotensin receptor
      blocker (ARB) use from 36.4% to 36.8%, beta-blockers from 19.1% to 21.1%, and
      thiazide diuretic use from at 11.5% to 12.8%. If treatment patterns had remained
      the same between 1997 and 1999 in terms of the proportion of medications from
      each drug class, an additional six million dollars would have been spent on
      antihypertensive medications in 1999. Although calcium antagonists and ACE
      inhibitors/ARB remained the most commonly dispensed antihypertensives at VA
      facilities from 1997 to 1999, there was a proportional decrease in calcium
      antagonist use and an increase in the use of thiazide diuretics and beta
      blockers. These changes were consistent with improved compliance with VA national
      guidelines. The cost implications of these changes in practice patterns were
      considerable.

PMID- 11587165
TI  - Pilot study to evaluate a water displacement technique to compare effects of
      diuretics and ACE inhibitors to alleviate lower extremity edema due to
      dihydropyridine calcium antagonists.
AB  - Combination therapy is required in many patients to achieve goal blood pressure
      (BP). Calcium antagonists are highly effective antihypertensive drugs in a broad
      range of demographic groups. Yet, higher doses are associated with an increased
      frequency of lower extremity edema. The purpose of our open label, single-center
      clinical trial was to evaluate the use of concomitant pharmacologic therapies to
      attenuate the lower extremity edema associated with dihydropyridine calcium
      antagonists therapy using a water displacement technique. Forty-seven patients
      received 5 mg/day of oral amlodipine for a period of 6 weeks after a 4-week wash
      out off of all antihypertensive medications to establish baseline BP. They were
      then randomized to receive either an additional 5 mg of amlodipine, 25 mg of
      hydrochlorothiazide (HCTZ), or 20 mg of benazepril for an additional 6 weeks.
      Blood pressure determinations and water displacement measurements were obtained
      at the end of the 4-week placebo wash-out period, after 6 weeks of 5 mg/day of
      oral amlodipine therapy, and after an additional 6 weeks of 5 mg of amlodipine
      and randomized drug therapy. Adjusted BP reductions (based on pretreatment BP)
      were -6.8/-3.8 mm Hg for the 10-mg amlodipine group, -9.9/-8.2 mm Hg for the
      amlodipine (5 mg)/HCTZ (25 mg) group, and -26.2/-16.4 mm Hg for the amlodipine (5
      mg)/benazepril (20 mg) group (P < .0167, group 3 v group 1 diastolic BP, which
      was statistically significant by the improved Bonferroni method). Seventeen of
      the 47 patients developed at least a 10% increase in lower extremity edema water
      displacement in response to 5 mg/day of oral amlodipine therapy (36.2%). Adding 5
      mg of amlodipine to a baseline of 5 mg of amlodipine resulted in no net change in
      lower extremity edema (+58.0 mL,+ 0.6% change, n=5). Adding 25 mg of HCTZ reduced
      lower extremity edema by a mean of 136.3 mL (-11.1% change, n=4). Benazepril
      reduced water displacement by 204.4 mL (-14.3% change, n=8). Our pilot study
      indicates that adding an angiotensin converting enzyme inhibitor to a
      dihydropyridine calcium channel blocker is the most effective way to not only
      reduce systolic and diastolic BP but also attenuate lower extremity edema. Due to
      the inherent daily variability of lower extremity edema, power calculations
      indicate many patients (n=702, 356 in each group) would be needed to compare the
      antiedema efficacy of the angiotensin converting enzyme inhibitor and the
      thiazide diuretic.

PMID- 11587166
TI  - Classic Images in hypertension. Hypertensive heart disease in a patient admitted
      to hospital with dyspnea, chest pain, and severe hypertension.

PMID- 11587167
TI  - Herbs and alternative therapies in the hypertension clinic.
AB  - The use of alternative therapies, herbs, and supplements occurs at a very high
      rate among patients attending a variety of health care settings. Such therapy may
      cause significant interactions or effects on hypertension and other
      cardiovascular disorders and needs to be considered by clinicians. In this brief
      review, we highlight several commonly used alternative therapies that may have a
      clinical impact in the hypertensive patient. Several problems hinder our complete
      awareness of these effects. These problems include patients not informing
      physicians about alternative treatment or herbal use, the lack of consistent
      scientific standards for the bioactivity of many herbals or supplements, and the
      multiple names that each bioactive substance is sold under. Specific questioning
      regarding herbals and alternative therapies in the hypertension clinic is
      therefore needed. Herbals including ma huang, St. John's wort, yohimbine, garlic,
      and licorice all may cause important consequences in the hypertensive patient.
      Added care is needed in monitoring the use and effects of herbal and alternative
      therapies in the hypertensive population.

PMID- 11587168
TI  - Measurement of blood pressure in children.

PMID- 11587169
TI  - Vasodilatory edema: a common side effect of antihypertensive therapy.

PMID- 11587170
TI  - Mind the gap: prevalence and pathophysiology of isolated systolic hypertension.

PMID- 11587171
TI  - Hang-back recession.

PMID- 11587172
TI  - Options for Marfan's syndrome.

PMID- 11587173
TI  - Differentiation of coats' disease and retinoblastoma.

PMID- 11587174
TI  - Strabismus measurements using the alternating and simultaneous prism cover tests:
      a comparative study.
AB  - PURPOSE: To determine the most accurate method of strabismus measurement in
      patients with constant manifest esotropia. METHODS: Patients underwent routine
      cover test assessment with the cover-uncover test and the alternating cover test
      with any increase in the angle of deviation being noted between the two methods.
      The simultaneous and alternating prism cover test was then performed to see if a
      qualitative increase in angle deviation was represented by a quantitative
      measurement. Patients also were assessed for the presence of binocular vision in
      free space using Bagolini striated lenses and motor fusion responses to base out
      prisms. RESULTS: There was a significant difference between the alternating and
      simultaneous prism cover test measurements for all patients (mean difference for
      near fixation: 4.72 prism diopters [delta]; 95% confidence interval [CI], 1.68
      7.75 delta; df=51; P<.001). For patients who showed a qualitative change in angle
      based on observational judgement using the cover tests, the mean difference in
      angle measured by simultaneous and alternating prism cover test for near fixation
      was 7.42 delta (95% CI, 5.75-10.30 delta; df=25; P<.001). CONCLUSION: To obtain
      an accurate interpretation of the size of manifest esotropia, the angle of
      deviation needs to be measured by the simultaneous and alternating prism cover
      test when an observable difference is noted on the cover test. The presence of a
      latent component to a manifest deviation should prompt the investigation of
      binocular reflexes even if the manifest angle is too large to be commensurate
      with binocular vision.

PMID- 11587175
TI  - Comparison of hang-back and conventional recession surgery for horizontal
      strabismus.
AB  - PURPOSE: To compare the results of hang-back and conventional recession surgery.
      METHODS: This randomized, double-blind, matched clinical trial comprised 30
      patients with esotropia and 24 with exotropia. All ocular examinations before and
      at least 1.5 months after surgery were performed by an orthoptist who was unaware
      of the method of recession. All surgeries were performed by the same surgeon.
      RESULTS: In patients with esotropia, deviation improved from 31+/-9 prism
      diopters (delta) preoperatively to 7+/-6 delta postoperatively for hang-back
      recession (n=15) and from 41+/-14 delta to 6+/-6 delta for conventional recession
      (n=15). Postoperative horizontal deviation was >10 delta in 40% of patients who
      underwent hang-back recession and 20% of patients who underwent conventional
      recession (P<.8). In patients with exotropia, deviation improved from 28.9+/-9
      delta preoperatively to 0.5+/-11 delta postoperatively for hang-back recession
      (n=12) and from 29+/-8 delta to 6+/-6 delta for conventional recession (n=12).
      Postoperative horizontal deviation was >10 delta in 24% of patients who underwent
      hang-back recession and 17% of patients who underwent conventional recession
      (P<.2). Mean follow-up was 7 months. CONCLUSION: Hang-back recession is an
      alternative to conventional rectus muscle recession, especially in children who
      have smaller globes and patients with myopia or collagen vascular diseases.

PMID- 11587176
TI  - Retinal detachment associated with subthreshold retinopathy of prematurity.
AB  - PURPOSE: To report a series of infants who progressed from mild retinopathy of
      prematurity (ROP) to severe ROP with retinal detachment without demonstrating
      detectable threshold disease. METHODS: Between January 1993 and August 1998,
      seven infants at Oregon Health Sciences University, followed in accordance with
      the Cryotherapy for Retinopathy of Prematurity Study (CRYO-ROP) protocol,
      progressed to retinal detachment despite documentation that threshold had not
      been reached. This outlying subset of patients was analyzed and compared to the
      cohort in the CRYO-ROP study. RESULTS: Six of 7 patients were male, 6 (86%)
      patients had symmetric disease, and all patients were born outside the study
      hospital. Mean birth-weight was 877 g and mean gestational age was 26 weeks. Mean
      postconceptual age at the time of retinal detachment was 41 weeks. Because of
      bilateral detachment in 3 patients, the total number of study eyes is 10. Failure
      to achieve threshold resulted from insufficient clock hours or insufficient stage
      in 2 eyes and lack of plus in 8 eyes. Zone I disease was present in 1 eye.
      CONCLUSION: Rarely, despite adhering to ROP examination protocol, the retina may
      detach without demonstrating antecedent threshold disease. Very low birthweight
      is a factor that may lead to a less predictable course. This study found a lack
      of plus disease results in failure to reach threshold more often than the
      occurrence of insufficient clock hours of stage 3 disease. Further study is
      needed to determine if selected cases of subthreshold ROP may benefit from
      ablative therapy.

PMID- 11587177
TI  - The moving Dynamic Random Dot Stereosize test: development, age norms, and
      comparison with the Frisby, Randot, and Stereo Smile tests.
AB  - PURPOSE: To determine the response of infants and children to the Moving Dynamic
      Random Dot Stereosize (MDRS) test and to collect cross-sectional age-related
      data. METHODS: Sixty visually normal individuals were divided into four age
      groups: 0.5-<2, 2-<5, 5-<8, and 8-<20 years. Stereopsis was measured with the
      MDRS test on two occasions, plus the Frisby, Randot, or Stereo Smile tests, as
      was age appropriate. RESULTS: All children aged >2 years and 80% of the children
      between ages 6 months and 2 years were able to perform the MDRS test on at least
      one occasion. Sixty percent of the 6-month to 2-year-old children were able to
      perform the Stereo Smile test on both occasions. Performance on the MDRS test
      improved with age up to 9 years. Improvement on the Frisby and Randot tests was
      seen in children aged up to 7 years. Mean and 95% confidence interval ranges for
      each test are given. CONCLUSION: This study gives evidence that aspects of the
      visual system are not fully mature until age 7-9 years. The MDRS test is a
      visually demanding but cognitively simple test that shows potential for detecting
      visual anomalies in young children.

PMID- 11587178
TI  - Clinicopathologic factors related to apoptosis in retinoblastoma.
AB  - PURPOSE: To investigate the presence of apoptosis in retinoblastoma and its
      correlation with other pathologic and prognostic factors. METHODS: The pathologic
      and admission records of 25 patients with a pathologically confirmed diagnosis of
      retinoblastoma were reviewed. TUNEL (TdT dUTP nick end labeling) staining was
      used to examine apoptosis in the pathologic slides of these 25 patients. The
      association between apoptosis and clinicopathologic factors was examined with chi
      square, Fisher's exact, and Student's t tests. RESULTS: Of the 25 specimens
      tested, 11 were TUNEL stain-positive for the presence of apoptotic cells.
      Apoptosis was found more frequently in younger patients and within rosettes,
      although these associations were not statistically significant. Apoptosis was not
      associated with tumor invasion or metastasis. CONCLUSION: Apoptotic cells were
      found in 11 of 25 retinoblastoma specimens. Apoptosis tends to occur in young
      patients and be distributed within rosettes.

PMID- 11587179
TI  - Perioperative and postoperative use of antibiotics and steroids in strabismus
      surgery.

PMID- 11587180
TI  - Congenital cleavage of the dorsal pons and medulla.

PMID- 11587181
TI  - Lens cyst discovered by school photoscreening.

PMID- 11587182
TI  - Eye involvement in hyperimmunoglobulinemia E (Job's) syndrome.

PMID- 11587183
TI  - Gastroesophageal reflux disease presenting as xerophthalmia.

PMID- 11587185
TI  - Synthesis and spectroscopic characterization of protected N
      phosphonomethylglycine dipeptides.
AB  - A series of terminally blocked dipeptides containing C-terminal N
      phosphonomethylglycine (glyphosate, an extremely effective non-selective post
      emergence herbicide) have been synthesized by a solution method. The presence of
      their two conformers, cis (syn) and trans (anti), was shown in solutions by NMR
      spectroscopy. Molecular structures of the peptides were also determined in the
      solid state by X-ray diffraction. The attempts for the selective and total
      removal of the groups protecting amino, carboxylic and phosphonate functions were
      in many cases unsuccessful due to the formation of cyclic structures and breakage
      of the phosphorus-to-carbon bond.

PMID- 11587184
TI  - Design of oxytocin antagonists, which are more selective than atosiban.
AB  - We report the solid phase synthesis of four pairs of L- and D-thienylalanine
      (Thi/D-Thi) position two modified analogues of the following four oxytocin (OT)
      antagonists: des-9-glycinamide [1-(beta-mercapto-beta,beta-pentamethylene
      propionic acid), 2-O-methyltyrosine, 4-threonine]ornithine-vasotocin
      (desGly(NH2)9,d (CH2)5[Tyr(Me)2,Thr4]OVT) (A); the Tyr-(NH2)9 analogue of (A),
      d(CH2)5[Tyr(Me)2,Thr4,Tyr-(NH2)9]OVT (B); the Eda9 analogue (where Eda =
      ethylenediamine) of (A), d(CH2)5[Tyr(Me)2, Thr4, Eda9]OVT (C); and the retro
      Tyr10 modified analogue of (C), d(CH2)5[Tyr(Me)2, Thr4, Eda9<--Tyr10]OVT (D). The
      eight new analogues of A-D are (1) desGly(NH2),d(CH2)5[Thi2,Thr4]OVT, (2)
      desGly(NH2),d(CH2)5[D-Thi2,Thr4]OVT, (3) d(CH2)5[Thi2, Thr4,Tyr-(NH2)9]OVT, (4)
      d(CH2)5[D-Thi2,Thr4,Tyr-(NH2)9]OVT (5) d(CH2)5[Thi2,Thr4Eda9]OVT, (6) d(CH2)5[D
      Thi2,Thr4,Eda9]OVT, (7) d(CH2) [Thi2,Thr4,Eda9<--Tyr10]OVT, (8) d(CH2),[D
      Thi2,Thr4,Eda9<--Tyr10]OVT. We also report the synthesis of (C). Peptides 1-8 and
      C were evaluated for agonistic and antagonistic activities in in vitro and in
      vivo OT assays, in in vivo vasopressor (V1a receptor) assays and in in vivo
      antidiuretic (V2 receptor) assays. None of the eight peptides nor C exhibit
      oxytocic or vasopressor agonism. Peptides 1-8 are extremely weak V2 agonists
      (antidiuretic activities range from < 0.0005 to 0.20 U/mg). Peptide C is a weak
      mixed V2 agonist/antagonist. Peptides 1-8 and C exhibit potent in intro (no Mg2+)
      OT antagonism (anti-OT pA2 values range from 7.76 to 8.05). Peptides 1-8 are all
      OT antagonists in vivo (estimated in vivo anti-OT pA2 values range from 6.54
      7.19). With anti-V1a pA2 values of approximately 5-5.80, peptides 1-8 exhibit
      marked reductions in anti-V1a potencies relative to those of the parent peptides
      A-D (anti-V1a pA2 range from 6.48 to 7.10) and to l-deamino[D-Tyr(Et)2, Thr4]OVT
      (Atosiban, trade name Tractocile) (anti-V1a pA2-6.14). Atosiban has recently been
      approved in Europe for clinical use for the prevention of premature labour
      (Pharm. J. 264(7-100): 871). Peptides 1-8 exhibit striking gains in in vitro anti
      OT/anti-V1a selectivities with respect to the parent peptides A, B, C and D and
      to Atosiban. Peptides 1-8 exhibit anti-OT (in vitro)/anti-V1a selectivities of
      450, 525, 550, 450, approximately 1080, 116, 355, 227 respectively. The
      corresponding values for A-D and Atosiban are 30, 4.2, 4.3, 2.6 and 37. With the
      exception of peptide 6, the remaining seven peptides exhibit 3-18-fold gains in
      anti-OT (in vivo)/anti-V1a selectivity with respect to Atosiban, peptides 1-8
      exhibit anti-OT (in vivo)/anti-V1a selectivities of 22, approximately 82,
      approximately 82, 147, approximately 83, 11, 31 and 42. By comparison, Atosiban
      exhibits an anti-OT (in vivo)/anti-V1a selectivity = 8. With an estimated in vivo
      anti-OT pA2 value = 7.19+/-0.06, peptide 4 is equipotent with Atosiban (pA2 =
      7.05+/-0.05). However, with its significantly reduced anti-vasopressor potency,
      pA2 = approximately 5, it is approximately 18 times more selective for OT
      receptors with respect to VP V1a receptors than Atosiban. Since we have shown
      that V1a antagonism could be an unwanted side-effect in tocolytics, peptide 4 and
      some of the OT antagonists reported here have advantages over Atosiban and thus
      may be suitable candidates for evaluation as potential tocolytic agents for the
      treatment of preterm labour.

PMID- 11587186
TI  - Polypeptide synthesis using an expressed peptide as a building block for
      condensation with a peptide thioester: application to the synthesis of
      phosphorylated p21Max protein(1-101).
AB  - An expressed peptide proved to be useful as a building block for the synthesis of
      a polypeptide via the thioester method. A partially protected peptide segment,
      for use as a C-terminal building block, could be prepared from a recombinant
      protein; its N-terminal amino acid residue was transaminated to an alpha-oxoacyl
      group, the side-chain amino groups were then protected with t-butoxycarbonyl
      (Boc) groups, and. finally, the alpha-oxoacyl group was removed. On the other
      hand, an O-phosphoserine-containing peptide thioester was synthesized via a solid
      phase method using Boc chemistry. These building blocks were then condensed in
      the presence of silver ions and an active ester component. During the
      condensation, epimerization at the condensation site could be suppressed by the
      use of N,N-dimthylformamide (DMF) as a solvent. Using this strategy, a
      phosphorylated partial peptide of the p21Max protein, [Ser(PO3H2)2.11]-p21Max(1
      101), was successfully synthesized.

PMID- 11587187
TI  - Improved preparation of amyloid-beta peptides using DBU as Nalpha-Fmoc
      deprotection reagent.
AB  - Previous studies have shown the amyloid peptides, Abeta 1-40/42, to be
      exceptionally difficult to assemble by Fmoc-solid phase peptide synthesis due to
      the high hydrophobicity of the C-terminal segment and resulting on-resin
      aggregation. We found that the use of the stronger and more efficient base, DBU,
      at a concentration of 2% in DMF for Nalpha-Fmoc deprotection allowed
      substantially improved continuous flow solid phase assembly of the model peptide
      Abeta 29-40/42 fragments. This suggested that, at least for these sequences,
      incomplete deprotection was a greater problem than incomplete amino acid
      acylation. This base was then used during the synthesis of both Abeta 1-40 and
      Abeta 1-42, up to and including Ser8, from which point 20% piperidine in DMF was
      utilized so as to avoid potential aspartimide formation at Asp7. By this means,
      the deprotection efficiency through the difficult C-terminal portion of the
      sequence was much improved and resulted in increased availability of terminal
      amino groups for acylation. This simple strategy that obviates the need for
      special conditions significantly improved crude peptide quality and allowed
      considerable facilitation of subsequent purification.

PMID- 11587189
TI  - Synthesis and application of Fmoc-His(3-Bum)-OH.
AB  - This paper presents a reevaluation of the synthesis and properties of Fmoc-His(3
      Bum)-OH regarding its application in SPPS with minimal racemization of histidine
      residues during coupling and esterification reactions. By-product formation
      during the deprotection of the test peptides could be significantly reduced by
      scavenging the concomitantly formed HCHO, e.g. with methoxyamine.

PMID- 11587188
TI  - Chemical synthesis and biological activity of rat INSL3.
AB  - The recently identified protein, insulin 3 (INSL3), has structural features that
      make it a bona fide member of the insulin superfamily. Its predicted amino acid
      sequence contains the classic two-peptide chain (A- and B-) structure with
      conserved cysteine residues that results in a disulphide bond disposition
      identical to that of insulin. Recently, the generation of insl3 knockout mice has
      demonstrated that testicular descent is blocked due to the failure of a specific
      ligament, the gubernaculum, to develop. The mechanism by which INSL3 exerts its
      action on the gubernaculum is currently unknown. The purpose of this study was
      to, for the first time, synthesize rat INSL3 and test its action on organ
      cultures of foetal rat gubernaculum. INSL3 also contains a cassette of residues
      Arg-X-X-X-Arg within the B-chain, a motif that is essential for characteristic
      activity of another related member of the superfamily, relaxin. Hence, the
      relaxin activity of rat INSL3 was also tested in two different relaxin bioassays.
      The primary structure of rat INSL3 was determined by deduction from its cDNA
      sequence and successfully prepared by solid phase peptide synthesis of the two
      constituent chains followed by their combination in solution. Following
      confirmation of its chemical integrity by a variety of analytical techniques,
      circular dichroism spectroscopy confirmed the presence of high beta-turn and
      alpha-helical content, with a remarkable spectral similarity to the synthetic
      ovine INSL3 peptide and to synthetic rat relaxin. The synthetic rat INSL3 bound
      with very low affinity to rat relaxin receptors and had no activity in a relaxin
      bioassay. Furthermore, it did not augment or antagonize relaxin activity. The rat
      INSL3 did however induce growth of foetal rat gubernaculum in whole organ
      cultures demonstrating that INSL3 has a direct action on this structure.

PMID- 11587190
TI  - Study of different coupling agents in the conjugation of a V3-based synthetic MAP
      to carrier proteins.
AB  - The conjugation of synthetic peptides to carrier proteins is a widely used method
      for immunological studies. Different coupling agents have been described to form
      the conjugate with carrier proteins. In this paper, we demonstrate that the
      antibody response toward V3-based synthetic MAPs derived from HIV-1, JY1 isolate,
      conjugated to two different carrier proteins using either m-maleimidobenzoyl-N
      hydroxysuccinimide ester (MBS) or beta-maleimidopropionic acid N
      hydroxysuccinimide ester (MPS), or succinic anhydride (SA) show different
      behaviors. An excellent anti-JY1 response without a strong response to the
      coupling agent is observed in the case of succinic anhydride spacer. In contrast,
      MBS produces total abrogation of the antibody response with a high response
      toward the coupling agent.

PMID- 11587191
TI  - The struggles of doing what is right and needed.

PMID- 11587192
TI  - Texas entry-year agriculture teachers' perceptions, practices, and preparation
      regarding safety and health in agricultural education.
AB  - The purpose of this study was to gather benchmark data for the assessment of the
      knowledge, attitudes, and perceptions regarding agricultural safety issues and
      curricula held by Texas agricultural teachers with less than two full years of
      teaching experience (entry-year teachers). Seventy-four of 118 well-distributed
      teachers responded to this survey. Researchers concluded that more females were
      entering a traditionally male-dominated field. Overall, teachers addressed safety
      within units of instruction rather than as separate units. The most useful forms
      of new teaching resources that this group of teachers would like to see produced
      were safety videos and study guides, and class demonstration/simulation
      activities. There was a significant difference in rankings between teachers less
      than 26 years old and teachers more than 26 years old regarding the usefulness of
      transparencies as a new teaching resource (F = 5.00, p = 0.0268). Few teachers
      were currently CPR and first aid certified, even though most had received
      training and completed a general safety and/or health related course while in
      college. Teachers generally agreed philosophically with most practices and
      exhibited personal beliefs consistent with proper safety preparedness and
      practice in agricultural settings. However, many of these teachers failed to
      practice what was expected of safe tractor operators, such as wearing safety
      belts and allowing younger drivers to operate the equipment.

PMID- 11587193
TI  - Tractor driving among kentucky farm youth: results from the farm family health
      and hazard surveillance project.
AB  - This article documents the extent of children's involvement in tractor operations
      among a representative sample of Kentucky children living and working on family
      farms. Specifically, we describe children's exposures to tractor-related work
      activities, profile their use of the tractor (number of days worked), and assess
      compliance with generally recommended safety measures, such as using tractors
      equipped with ROPS (rollover protective structures), avoiding riding as
      passengers on tractors, and operating tractors on public roadways. Data for this
      study were collected in 1994 and 1995 as part of the NIOSH-sponsored Farm Family
      Health and Hazard Surveillance Project (FFHHSP). Despite recognition in the
      health and safety community of the hazards associated with operating tractors
      without ROPS on public roadways and with extra riders, these practices remain
      common among youth on Kentucky farms. Farms with annual incomes greater than
      $10,000, particularly with livestock commodities, appear to use youth for a
      greater number of days of tractor operation than other farms. Such farms may be
      an appropriate target for intervention.

PMID- 11587194
TI  - Summary of fatal entrapments in on-farm grain storage bins, 1966-1998.
AB  - For over 30 years, Purdue University has maintained a national database of
      agriculture-related entrapment cases that have occurred in loose agricultural
      material. At present, 391 documented fatal and non-fatal entrapments from the
      U.S. and Canada make up the Purdue University Agricultural Entrapment Database.
      In order to specifically study fatal cases of entrapments in grain bins located
      on farms, the database was reviewed, 181 cases were identified using specific
      criteria, and the results were summarized. Approximately five cases per year were
      identified between 1966 and 1998, representing 18 states and one Canadian
      province. Entrapments were generally reported more often in the top corn
      producing states and during the months of November, December, January, March, and
      June. In 24% of the cases in which the victim's age was known, the victims were
      younger than 16. Children and adolescents younger than 16 were more often fatally
      entrapped in June than in any other month. For cases in which the product was
      known, corn was the agent of injury in 53% of the cases and was frequently found
      to be out-of-condition. At the time of entrapment, victims were involved with bin
      unloading activities in 76% of the cases in which the activity was identified.
      These findings are being used to design new injury prevention strategies,
      including educational materials and recommendations for engineering controls that
      focus on primary causative factors.

PMID- 11587196
TI  - Similar survival rates for ocular melanoma therapies.

PMID- 11587195
TI  - An instrument to measure musculoskeletal symptoms among immigrant Hispanic
      farmworkers: validation in the nursery industry.
AB  - We report on the construction and psychometrics of a survey measure of
      musculoskeletal symptomatology for use with Spanish-speaking immigrant
      farmworkers. Survey development included focus groups with workers, forward and
      backward translations, and pilot testing. The final survey includes a body
      diagram and items about symptom severity, frequency, and duration and about self
      treatment, medical care, and job tasks. We report on the initial test of the
      survey with 213 commercial nursery workers in Southern California. Fifty-five
      percent of the workers reported pain, with 30% reporting back pain, 21% reporting
      upper extremity pain, 19% reporting lower extremity pain, and 10% reporting neck
      and shoulder pain. A composite symptom score exhibited acceptable test-retest
      reliability (r = 0.41, p < 0.01) over the annual agricultural cycle. Greater
      symptomatology was associated with greater frequency of self-treatment (r = 0.42,
      p < 0.01), seeking professional health care (t = 2.49, p < 0.05), and exposure to
      high-risk jobs (OR = 2.1, p < 0.05, CI = 1.0 to 4.4), supporting the validity of
      composite score.

PMID- 11587197
TI  - Non-Hodgkin's orbital lymphoma.
AB  - BACKGROUND: The non-Hodgkin's lymphomas (NHL) are a group of neoplasms
      characterized by proliferation of malignant lymphocytes. Patients with NHL have a
      wide variety of presenting signs and symptoms, depending largely on the site of
      involvement and aggressiveness of the disease. Many organs in the body may be
      affected, including the eye and orbit. CASE REPORT: A 47-year-old male with a 3
      year history of stage IV non-Hodgkin's lymphoma who had undergone recent
      monoclonal antibody therapy presented with a complaint of blur in the left eye
      with occasional diplopia. Significant ocular findings of the left eye included
      ptosis, mild proptosis, increased intraocular pressure, and choroidal folds.
      Magnetic resonance imaging of the orbit revealed an orbital lymphoma that
      completely resolved after 2400 rads of external beam irradiation therapy. Eight
      months later, the patient developed a secondary radiation retinopathy.
      CONCLUSION: The prevalence of NHL is on the rise, and orbital involvement may
      occur at any time during the course of the disease. The standard treatment for
      non-Hodgkin's orbital lymphoma is external beam irradiation therapy, although the
      optimal dose for obtaining local tumor control without complications remains to
      be determined. Non-Hodgkin's lymphoma, orbital lymphoma, and various treatment
      options are discussed.

PMID- 11587198
TI  - Monovision: a review of the scientific literature.
AB  - We reviewed the scientific literature on monovision to compare the visual
      performance of monovision patients with that of others wearing more traditional
      prescriptions. We found that visual performance of monovision patients was
      comparable to that of control patients wearing a balanced binocular correction,
      provided that reading adds were not greater than about +2.5 D, that illumination
      was photopic, and that stimuli were presented at supra-threshold levels. Under
      these conditions, monovision patients were satisfied with their perceptual
      experience and performed within 2 to 6% of balanced binocular control patients on
      a range of occupational tasks. It is noteworthy that monovision patients had
      relatively more difficulty with acuity-based tasks than with tasks demanding good
      depth perception. With reading adds over +2.5 D, at low levels of illumination,
      or with near-threshold level stimuli, visual performance of monovision patients
      was reduced compared with controls. Subjectively, under low levels of
      illumination, monovision patients experienced problems with glare and halos
      around point sources of light.

PMID- 11587199
TI  - The effect of degree of refractive error on hydrogel contact lens-induced
      complications and patient self-management behaviors.
AB  - INTRODUCTION: Although many aspects of hydrogel lens wear have been explored over
      the last 20 years, little attention has been paid to the role of refractive error
      magnitude in determining patients' ocular responses or associated contact lens
      behaviors. METHODS: A cross-sectional study was conducted in 32 optometric and
      ophthalmologic practices. We enrolled 2161 spherical soft contact lens-wearing
      patients. High ametropes were defined as those with at least +/- 5.00 D spherical
      equivalent refractive error in the right eye. Data on current contact lenses,
      prescribed care regimens, and slit lamp biomicroscopic signs were provided by the
      eye care practitioners, and information on actual lens care behaviors and
      attitudes toward contact lens wear were gathered by survey directly from the
      patients. All differences between high and low ametropes were compared using the
      chi-square test. RESULTS: Compared with low ametropes, high ametropes were more
      satisfied with their vision with contact lenses (p < 0.001). More high ametropes
      wore their lenses on an extended-wear schedule (p = 0.015). Both groups of
      patients reported a similar degree of lens awareness and lens-associated pain,
      but fewer high ametropes reported foreign body sensation (p = 0.002). In managing
      contact lens discomfort, high ametropes were more likely to use an old spare lens
      (p = 0.01) and more likely to continue wearing their lenses (p = 0.016)-
      indicators of a propensity for self-management. In response to a damaged lens,
      high ametropes were less likely to remove both of their lenses (p = 0.002). High
      ametropes showed more conjunctival staining (p = 0.001) and more corneal scars (p
      = 0.033). High ametropes also presented with more corneal fluorescein staining (p
      = 0.001) and more corneal vascularization (p < 0.001). These relations between
      the degree of ametropia and slit lamp signs of contact lens wear were not
      significantly affected by daily- vs. extended-wear status. CONCLUSIONS: In
      summary, practitioners should consider the implications of the patient's degree
      of ametropia when prescribing contact lenses. These results indicate the need for
      closer observation and specific advice concerning management of contact lens
      related problems when caring for patients with high refractive errors.

PMID- 11587200
TI  - Does mobility performance of visually impaired adults improve immediately after
      orientation and mobility training?
AB  - BACKGROUND: Previous studies that have attempted to determine the effect of
      orientation and mobility training on mobility performance of visually impaired
      adults have had a number of limitations. With the inclusion of a control group of
      subjects, this study investigated the effect of orientation and mobility training
      on mobility performance of a group of visually impaired adults. METHODS: Vision
      was measured binocularly as high- and low-contrast visual acuity, letter and edge
      contrast sensitivity, and Humphrey kinetic visual fields. The subjects' mobility
      performance was assessed as percentage preferred walking speed (PPWS) and error
      score before and after mobility training. RESULTS: Orientation and mobility
      training did not enhance mobility performance compared with the control group,
      who did not receive training, when performance was measured immediately after
      training. PPWS improved for both groups with short-term practice only, but there
      was no improvement in error score due to either practice or training.
      CONCLUSIONS: There was no immediate improvement in mobility performance of
      visually impaired adults after orientation and mobility training. Familiarity
      with the route may play an important role in measured improvement of mobility
      performance after orientation and mobility training.

PMID- 11587201
TI  - Direction of gaze while walking a simple route: persons with normal vision and
      persons with retinitis pigmentosa.
AB  - PURPOSE: The purpose of this study was to determine whether persons with advanced
      vision impairment, when walking an unfamiliar route, visually sample the
      environment in a different manner than do persons with normal vision. METHODS:
      Direction of gaze was measured in six persons with retinitis pigmentosa (RP) and
      in three persons with normal vision as they walked an unfamiliar, obstacle-free
      route while viewing the environment in a head-mounted display. RESULTS: Persons
      with RP fixated over a larger area in the environment and at different features
      than did persons with normal vision. Persons with normal vision directed their
      gaze primarily ahead or at the goal, whereas persons with RP directed their gaze
      at objects on the walls, downward, or at the layout (i.e., edge-lines or
      boundaries between walls). The results also showed a significant negative
      correlation between the horizontal visual field extent of the RP subjects and the
      proportion of downward-directed fixations. CONCLUSIONS: Persons with advanced
      vision impairment as a result of RP visually sample the environment in a manner
      different from persons with normal vision.

PMID- 11587202
TI  - Aging effects on vernier hyperacuity: a function of oscillation rate but not
      target contrast.
AB  - PURPOSE: Most previous studies have shown static vernier acuity for high-contrast
      targets to be largely unaffected by aging; those examining adult age differences
      on oscillatory displacement thresholds have consistently reported marked age
      deficits. The goals of this study were to (1) measure the age deficit on
      oscillatory discrimination beyond that attributable to any change in spatial
      discrimination by using the same target configuration for both task types and (2)
      determine whether an age-related change in the contrast response of the visual
      system contributes to age differences on static or oscillatory discrimination.
      METHODS: The displacement thresholds of young and old observers for a vernier
      task configuration were determined at two target contrast levels (0.08 and 0.64)
      for static and oscillating targets (2 and 6 Hz) RESULTS: No age differences were
      seen on static displacement thresholds at either high or low contrast. A marked
      age deficit that emerged when oscillation was increased was unrelated to target
      contrast or observer contrast sensitivity. CONCLUSIONS: Age-related declines in
      oscillatory discrimination beyond those attributable to spatial discrimination do
      not appear to be attributable to optical factors nor to a decline in the contrast
      response of the senescent visual system. These findings are discussed in terms of
      a functional decline in the magnocellular pathway, or "neural entropy," possibly
      due to random cell loss.

PMID- 11587203
TI  - Improvements in measures of vision and self-reported visual function after
      cataract extraction in patients with late-stage age-related maculopathy.
AB  - PURPOSE: A recent study indicated that patients with cataracts and early age
      related maculopathy may benefit from cataract extraction. To ascertain whether
      cataract extraction in the presence of concurrent advanced age-related
      maculopathy was also associated with a clear benefit, we studied visual function
      and self-reported visual functioning in a cohort of 12 patients pre- and post
      phakoemulsification. METHODS. All 12 patients had a diagnosis of advanced age
      related maculopathy in the eye scheduled for cataract surgery. Preoperative
      assessment included refraction and recording of best corrected distance and near
      acuity and contrast sensitivity in both eyes. The Daily Living Tasks Dependent on
      Vision questionnaire was administered. After phakoemulsification and intraocular
      lens implantation, all patients were reviewed and assessed. RESULTS: After
      surgery, improvement in acuity was recorded in nine operated eyes, whereas acuity
      remained unchanged in three eyes. Improvement in contrast sensitivity in the
      operated eye occurred in 10 patients, but in two patients contrast was reduced
      postoperatively. In terms of self-reported visual functioning, improvement in the
      ability to undertake many daily living tasks dependent on vision was recorded
      after cataract surgery. CONCLUSIONS: Significant improvements in specific areas
      of self-reported visual functioning and measures of vision were recorded after
      cataract surgery. During the follow-up period, none of the operated eyes suffered
      a fall in visual acuity. There was also no evidence of worsening of the pre
      existing macular lesion as judged by clinical examination and fundus photography.

PMID- 11587204
TI  - The stem cell in the pathogenesis and treatment of myelogenous leukemia: a
      perspective.

PMID- 11587205
TI  - A new recurrent and specific cryptic translocation, t(5;14)(q35;q32), is
      associated with expression of the Hox11L2 gene in T acute lymphoblastic leukemia.
AB  - FISH identified a cryptic t(5;14)(q35;q32) in T acute lymphoblastic leukemia
      (ALL), whereas it was not observed in B ALL samples. This translocation is
      present in five out of 23 (22%) children and adolescents with T ALL tested.
      RanBP17, a gene coding for a member of the importin beta protein family, and
      Hox11Like2, an orphan homeobox gene were mapped close to the chromosome 5
      breakpoints and CTIP2, which is highly expressed during normal T cell
      differentiation, was localized in the vicinity of the chromosome 14 breakpoints.
      The Hox11L2 gene was found to be transcriptionally activated as a result of the
      translocation, probably under the influence of CTIP2 transcriptional regulation
      elements. These data establish the t(5;14)(q35;q32) as a major abnormality, and
      Hox11 family member activation as an important pathway in T ALL leukemogenesis.

PMID- 11587206
TI  - Recombinant urate oxidase (rasburicase) in the prevention and treatment of
      malignancy-associated hyperuricemia in pediatric and adult patients: results of a
      compassionate-use trial.
AB  - To confirm the efficacy of recombinant urate oxidase (rasburicase) and to
      establish its safety profile, we reviewed the data on 173 children and 72 adults
      with malignancy who were treated with this new uricolytic agent in a
      compassionate-use trial. Rasburicase (0.20 mg/kg) was administered intravenously
      daily for 1 to 7 days and could be given every 12 h for the initial 72 h.
      Subsequent courses were allowed at a later date. Rasburicase produced a dramatic
      decrease in uric acid concentrations in all patients whether they received it for
      prophylaxis (n = 79) or treatment (n = 166) (P < 0.001 in all comparisons between
      the levels at diagnosis and those after treatment). The median post-treatment
      levels were 0.5 to 0.7 mg/dl. Repeated administrations were also effective in all
      11 evaluable patients. Four children and five adults had mild adverse reactions
      that were drug related or of unknown etiology. In two of the children, the
      adverse events occurred during the second course. Rasburicase is highly effective
      and safe in the prophylaxis or treatment of malignancy- or chemotherapy
      associated hyperuricemia in children and adults.

PMID- 11587207
TI  - Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy
      in chronic lymphocytic leukemia.
AB  - The objective of the study was to determine the effectiveness and the toxicity of
      a combined chemotherapy consisting of cladribine (2-CdA), mitoxantrone and
      cyclophosphamide (CMC regimen) in the treatment of previously untreated B cell
      chronic lymphocytic leukemia (B-CLL). From August 1998 to December 2000 2-CdA was
      administered at a dosage of 0.12 mg/kg for 3 (CMC3) or 5 (CMC5) consecutive days,
      mitoxantrone at 10 mg/m2 on day 1 and cyclophosphamide at 650 mg/m2 on day 1 to
      62 patients with advanced or progressive B-CLL. The cycles were repeated at 4
      week intervals or longer if severe myelosuppression occurred. Twenty patients
      received CMC5 and 42 patients CMC3. Within the analyzed group an overall response
      (OR) rate (CR+PR) of 64.5% (95% CI: 52.7-76.3%) was reported, including 29.0% CR.
      There was no difference in the CR rate between the patients treated with CMC5
      (30%) and CMC3 (28.6%) (P = 0.9), nor in the OR rate (55.0% and 69.0%,
      respectively, P = 0.3). Residual disease was identified in seven out of 18
      (38.9%) patients who were in CR, including two treated with CMC5 and five treated
      with CMC3 protocols. CMC-induced grade III or IV thrombocytopenia occurred in 12
      (19.4%) of patients, including four (20%) CMC5-treated and eight (19%) CMC3
      treated patients (P= 0.8). Neutropenia grade III or IV was observed in seven
      (35%) and 11 (26.2%) patients, respectively (P = 0.8). Severe infections,
      including pneumonia and sepsis, occurred more frequently after CMC5 (11 patients,
      55.0%) than CMC3 (10 patients, 28.6%) (P = 0.03) Fourteen patients died,
      including six treated with CMC5 and eight treated with CMC3 (30% and 19%,
      respectively). Infections were the cause of death in nine patients, including
      four in the CMC5 group and five in the CMC3 group. In conclusion, our results
      indicate that the CMC programme is an active combined regimen in previously
      untreated B-CLL patients; its efficiency seems to be similar to that observed
      earlier in B-CLL patients treated with 2-CdA as a single agent. However,
      toxicity, especially after CMC5 administration, is significant. Therefore, we
      recommend the CMC3 but not the CMC5 programme for further evaluation.

PMID- 11587208
TI  - In vitro effects of dexrazoxane (Zinecard) and classical acute leukemia therapy:
      time to consider expanded clinical trials?
AB  - Anthracyclines have been the backbone of acute leukemia therapy in the adult for
      many years, but little attention has been paid to the long-term toxicity of these
      agents in this disease because of the poor survival of this population of
      patients. Recent studies have examined dose-intensified daunorubicin with dosages
      as high as 95 mg/m2 daily x 3 in this population with the attendant concerns of
      both acute and chronic toxicity. We have examined three human leukemia cell lines
      in vitro, treated with either daunorubicin, mitoxantrone, with or without
      cytosine arabinoside in the presence of dexrazoxane to determine whether such
      treatment would be synergistic or antagonistic. AML-193, CRF-SB, and Molt-4 cell
      lines were grown to confluence, plated into microtiter dishes and incubated for
      72 h with varying concentrations of the above drugs. Cytotoxicity was determined
      by the MTT assay, and synergy or antagonism by median effect analysis.
      Dexrazoxane demonstrated additive or synergistic cytotoxic effects (CI <1) under
      most conditions. The triplet of daunorubicin, cytosine arabinoside, and
      dexrazoxane showed profound synergy in all three cell lines. These effects
      occurred at clinically achievable levels. If high dosages of anthracyclines are
      contemplated in this population, these preclinical data suggest that the addition
      of dexrazoxane to classical therapy is not antagonistic and thus may allow an
      investigation of the role of dexrazoxane as a cardiac protectant.

PMID- 11587209
TI  - The class II tumor-suppressor gene RARRES3 is expressed in B cell lymphocytic
      leukemias and down-regulated with disease progression.
AB  - The molecular pathogenesis of B cell chronic lymphocytic leukemia (B-CLL), the
      most common form of leukemia, remains unknown. We have used the mRNA differential
      display technique to analyze genes that may be involved in the
      development/progression of B-CLL. We have identified the tumor suppressor
      retinoic acid receptor responder 3 (RARRES3) as a B-CLL-related gene. RARRES3
      maps to chromosome band 11q23, a region frequently deleted in lymphoproliferative
      disorders. To assess the potential involvement of RARRES3 in leukemogenesis, we
      examined 24 cases of B-CLL, 10 of acute lymphocytic leukemia (ALL) and five
      related cell lines by RT-PCR and sequence analyses. We report a correlation
      between RARRES3 down-regulation and B-CLL progression. We also found decreased
      RARRES3 gene levels in ALL cases and in the five cell lines studied. We did not
      find mutations in any of the leukemia samples assayed, including those with 11q23
      deletion. These results indicate that RARRES3 may play a role in B-CLL
      progression.

PMID- 11587210
TI  - Heterogeneity of VH-JH gene rearrangement patterns: an insight into the biology
      of B cell precursor ALL.
AB  - Oligoclonal B cell proliferation, as defined by the presence of more than one
      leukemic clone, has been detected in approximately 20% to 30% of patients with
      acute lymphoblastic leukemia (ALL) using PCR or Southern blotting. An accurate
      assessment of these populations is required to avoid false negative measurements
      of minimal residual disease (MRD) in follow-up bone marrow (BM) samples of ALL
      patients. In this study, we analysed 29 ALL patients with two or more
      immunoglobulin heavy (IGH) chain gene rearrangements in the presentation samples
      using IGH fingerprinting PCR and sequence analysis. Thirty-nine (51%) of 76
      sequences (from 15 patients), shared no VNDNJ homology (ie different CDR3
      regions). In the remaining 14 patients, at least two related VH sequences were
      identified in each patient (identical DNJ sequences). Numerical abnormalities of
      chromosome 14 was detected in 10 patients. Eight patients were analysed at
      presentation and relapse. In four of them, expansion of a minor presentation
      clone was detected at relapse while the major presentation clone disappeared,
      confirming 'subclonal evolution'. Finally, in our cohort of patients, the
      presence of related or unrelated IGH clones did not influence overall survival.

PMID- 11587211
TI  - The Hsp90 inhibitor geldanamycin selectively sensitizes Bcr-Abl-expressing
      leukemia cells to cytotoxic chemotherapy.
AB  - The Bcr-Abl fusion protein drives leukemogenesis and can render leukemia cells
      resistant to conventional chemotherapy. Geldanamycin (GA), a drug which
      destabilizes Hsp90-associated proteins, depletes cells of Bcr-Abl, an Hsp90
      client, but not of Abl. Both HL60 cells transfected with Bcr-Abl and naturally
      Ph1-positive K562 leukemia cells are resistant to most cytotoxic drugs, but were
      found to be sensitive to GA. Furthermore, GA sensitized Bcr-Abl-expressing cells
      to doxorubicin (DOX) and paclitaxel (PTX). In contrast, in parental HL60 cells,
      90 nM GA inhibited PARP cleavage, nuclear fragmentation, and cell death caused by
      500 ng/ml DOX. Like GA, STI 571 (an inhibitor of the Abl kinase) sensitized Bcr
      Abl-expressing cells to DOX. Unlike GA, STI 571 did not antagonize the cytotoxic
      effects of DOX in parental HL60 cells. These results indicate that sensitization
      of Bcr-Abl-expressing cells, but not desensitization of HL60 cells, depends on
      inhibition of Bcr-Abl. Thus, GA differentially affects leukemia cells depending
      on their Bcr-Abl expression and selectively increases apoptosis in Bcr-Abl
      expressing cells.

PMID- 11587212
TI  - Activity and expression of the multidrug resistance proteins P-glycoprotein,
      MRP1, MRP2, MRP3 and MRP5 in de novo and relapsed acute myeloid leukemia.
AB  - The multidrug resistance proteins (MRPs) MRP1, MRP2, MRP3, MRP5 and P
      glycoprotein (P-gp) act in concert with each other to give a net resultant pump
      function in acute myeloid leukemia (AML). The aim of the present study was to
      analyze the activity of these proteins, which might be upregulated at relapse as
      compared with de novo AML due to clonal selection. The mRNA expression and
      activity of P-gp and the MRPs were determined with RT-PCR and flow cytometry, in
      conjunction with phenotype, as measured with the monoclonal antibodies CD34, CD38
      and CD33, in 30 paired samples of de novo and relapsed AML. P-gp and MRP activity
      varied strongly between the cases (rhodamine 123 efflux-blocking by PSC833: 5.4+/
      7.7, and carboxyfluorescein efflux-blocking by MK-571: 4.3+/-6.7, n = 60). P-gp
      and MRP activity were increased in 23% and 40% of the relapse samples, and
      decreased in 30% and 20% of the relapse samples, respectively (as defined by a
      difference of >2 x standard deviation of the assays). Up- or downregulation of
      mRNA expression was observed for MDR1 (40%), MRP1 (20%), MRP2 (15%), MRP3 (30%),
      and MRP5 (5%). Phenotyping demonstrated a more mature phenotype in 23% of the
      relapsed AML cases, and a more immature phenotype in 23% of the relapses, which
      was independent of the karyotypic changes that were observed in 50% of the
      studied cases. P-gp and MRP activity correlated with the phenotypic changes, with
      higher P-gp and MRP activities in less mature cells (r = -0.66, P < 0.001 and r =
      -0.31, P = 0.02, n = 58). In conclusion, this study shows that P-gp and MRP
      activity are not consistently upregulated in relapsed AML. However, P-gp and MRP
      activities were correlated with the maturation stage as defined by immune
      phenotype, which was observed to be different in 46% of the relapses.

PMID- 11587213
TI  - Functional characterization of minimal residual disease for P-glycoprotein and
      multidrug resistance protein activity in acute myeloid leukemia.
AB  - Relapse is common in acute myeloid leukemia (AML) due to persistence of residual
      leukemia cells: minimal residual disease (MRD). In 102 out of 127 patients (80%),
      cells at diagnosis displayed one or more leukemia-associated phenotypes (LAP), ie
      combinations of cell surface markers which are absent in normal cells and can
      thus be used to detect MRD at follow-up. Functional characterization of MRD cells
      for P-glycoprotein (Pgp) and multidrug resistance protein (MRP) activity is
      essential to investigate the role of these drug transport proteins in multidrug
      resistance in AML. A fluorescent probe assay using Syto16/PSC833 and calcein
      AM/probenecid as substrate/modulator of the Pgp and MRP pump, respectively, and
      subsequent labeling of cells with monoclonal antibodies for LAP detection allowed
      simultaneous detection of LAP and Pgp or MRP activity. Validation of this assay
      is shown for 30 newly diagnosed AML and 11 MRD situations. In addition, no
      significant differences were found when comparing fresh and cryopreserved de novo
      AML for LAP expression (n = 43), Pgp (n = 30) and MRP (n = 24) function and for
      MRD samples for simultaneous LAP expression and Pgp/MRP activity (n = 10). This
      approach enables longitudinal and multicenter studies on the detection,
      quantification and functional characterisation of MRD cells.

PMID- 11587214
TI  - Phosphodiesterase type 4 inhibitor suppresses expression of anti-apoptotic
      members of the Bcl-2 family in B-CLL cells and induces caspase-dependent
      apoptosis.
AB  - B cell chronic lymphocytic leukemia (B-CLL) is an incurable clonal disease which
      shows initial responsiveness to a number of chemotherapeutic drugs. However, in
      most patients the disease becomes resistant to treatment. Rolipram, a specific
      inhibitor of phosphodiesterase (PDE) type 4, the PDE predominantly expressed in B
      CLL cells, has been shown to induce cAMP-dependent apoptosis in these cells. In
      the present study, we demonstrate that the extent of rolipram-induced apoptosis
      is similar to fludarabine-induced apoptosis in vitro. The combination of rolipram
      and fludarabine results in an enhancement in the number of apoptotic cells
      compared to apoptosis induced by either agent alone. Second, rolipram suppresses
      the expression of anti-apoptotic members of the Bcl-2 family and induces the pro
      apoptotic protein Bax, thereby shifting the balance between pro- and anti
      apoptotic members of the Bcl-2 family towards a pro-apoptotic direction. Finally
      rolipram-induced apoptosis is caspase-dependent. PDE 4 inhibitors are currently
      under investigation for chronic obstructive pulmonary disease and asthma in phase
      III clinical trials showing promising results with tolerable side-effects. In
      conclusion, by inducing apoptosis, by enhancing apoptosis induced by fludarabine,
      by suppressing Bcl-2, Bcl-X and by inducing Bax expression, PDE 4 inhibitors may
      add a new therapeutic option for patients with B-CLL.

PMID- 11587216
TI  - Novel genomic imbalances and chromosome translocations involving c-myc gene in
      Burkitt's lymphoma.
AB  - In this study, CA46 and ST486, two Epstein-Barr (EBV) negative cell lines derived
      from sporadic BL, were analyzed by multicolor spectral karyotyping, G-banding,
      fluorescence in situ hybridization with single-copy gene probes, and comparative
      genomic hybridization (CGH). In addition to reciprocal t(8;14)(q24;q32)
      translocation involving c-myc and IgH loci, we identified a
      t(7;8;14)(q11.2;q24;q32) translocation in CA 46 cells and t(8;14;18)(q24;q32;q23)
      in ST486 cells. Both rearrangements were not previously described in BL and
      resulted in transposition of myc sequences in a new genomic configuration.
      Several DNA imbalances mapped by CGH at the same sites in both lines, may reflect
      recurrent genomic changes that are relevant to pathogenesis of BL. We tested the
      tumorigenicity of these lines by injecting cells intraperitoneally in SCID mice.
      In two separate experiments, CA46 cells produced tumors 2 weeks after cell
      inoculation while ST486 cells induced only one tumor after a long latency period.
      Partial duplication of the long arm of chromosome 1 involving variable bands but
      always band 1q23 is the second most common alteration in BL and is known to be
      associated with aggressive tumors and poor prognosis. Duplication of the bands
      1q23-24 commonly observed in EBV-negative lines was identified only in highly
      tumorigenic CA46 cells suggesting that this region harbor gene(s) associated with
      tumor cell invasiveness.

PMID- 11587215
TI  - Early increase in DcR2 expression and late activation of caspases in the platelet
      storage lesion.
AB  - Platelet transfusion is widely used to prevent bleeding in patients with severe
      thrombocytopenia. The maximal storage duration of platelet concentrates is
      usually 5 days, due to the platelet storage lesion that impairs their functions
      when stored for longer times. Some of the morphological and biochemical changes
      that characterize this storage lesion are reminiscent of cell death by apoptosis.
      The present study analyzed whether proteins involved in nucleated cell apoptosis
      could play a role in the platelet storage lesion. Storage of leukocyte-depleted
      platelets obtained by apheresis is associated with a late and limited activation
      of caspases, mainly caspase-3. This event correlates with an increased expression
      of the pro-apoptotic BH3-only protein Bim in the particulate fraction and a
      slight and late release of the pro-apoptotic mitochondrial protein Diablo/Smac in
      the cytosol. Platelets do not express the death receptors Fas, DR4 and DR5 on
      their plasma membrane, while the expression of the decoy receptor DcR2 increases
      progressively during platelet storage. Addition of low concentrations of the
      cryoprotector dimethylsulfoxide accelerates platelet caspase activation during
      storage, an effect that is partially prevented by the caspase inhibitor z-VAD
      fmk. Altogether, DcR2 expression on the plasma membrane is an early event while
      caspase activation is a late event during platelet storage. These observations
      suggest that caspases are unlikely to account for the platelet storage lesion. As
      a consequence, addition of caspase inhibitors may not improve the quality of
      platelet concentrates stored in standard conditions.

PMID- 11587218
TI  - An optimised biphasic culture system for the generation of functional dendritic
      cells from patients with acute lymphoblastic leukaemia at presentation and in
      clinical remission.
AB  - We have tested the hypothesis that functional dendritic cells (DC) may be
      generated from patients with acute lymphoblastic leukaemia (ALL). We evaluated
      the production of DC from blast cells taken at presentation from nine children
      with ALL. Blast cells were expanded in serum-free medium supplemented with Flt3L,
      G-CSF, GM-CSF, IL-3, IL-6 and SCF for 7 days and subsequently stimulated with
      Flt3L, GM-CSF and TGF-beta for a further 14 days, with the addition of TNF-alpha
      for the final 48 h of culture. Cultured cells had the morphological appearance of
      DC and expressed the DC-associated antigens CD1A (range 2-87%) and CD83 (15-44%).
      Expression of the co-stimulatory molecules CD80 and CD86 was increased and the
      majority of these cells retained their expression of CD34 (73+/-4%) and HLA-DR
      (79+/-5%). Seven of the nine ALL had a leukaemia-specific abnormality and DC
      generated from five of these seven cases were derived from the leukaemic clone.
      Leukaemic DC derived from four HLA-A*02-positive ALL pulsed with CMV-associated
      peptides could induce significant proliferation of peptide-specific CD8+ T cells.
      This specificity was verified using tetrameric complexes of HLA class l/antigenic
      peptide. DC could also be generated from cells taken at times of complete
      remission of ALL and from normal controls using these culture conditions. These
      findings show that functional DC can be generated both from ALL blasts and from
      patients in remission; these might be utilised in future for immunotherapeutic
      strategies in the treatment of ALL.

PMID- 11587217
TI  - P15INK4B gene methylation and expression in normal, myelodysplastic, and acute
      myelogenous leukemia cells and in the marrow cells of cured lymphoma patients.
AB  - P15INK4B methylation and expression was studied in bone marrow cells obtained
      from normal individuals, from patients who had been cured of lymphoma, and from
      patients with either MDS or AML. The level of p15 methylation was very low in
      normal BM cells and in CD34+ and CD34- subpopulations (0-6.5%; med, = 2.5%).
      P15INK4B transcripts were present in each of these cell populations. In contrast,
      methylation was the usual situation in MDS and AML marrows. The presence of
      methylation of the p15INK4B gene did not always indicate an absence of expression
      nor was expression always present if methylation was absent. P15INK4B methylation
      was studied in the marrows of nine patients (one studied twice) who had been
      cured of lymphoma and in whom hemopoiesis was believed to be normal. Increased
      methylaton was present in all 10 marrows. These data indicate that p15INK4B
      methylation is likely to be a very early event in the development of the
      secondary hematologic disorders.

PMID- 11587219
TI  - A PCR-based clonal analysis of radiation-induced loss of heterozygosity in
      haemopoietic stem cells.
AB  - CBA mouse strains have been used for many years as a model of radiation-induced
      acute myeloid leukaemia and the leukaemias in CBA and their F1 hybrids are
      characterised by a specific loss of heterozygosity involving one homologue of
      chromosome 2. Previous cytogenetic studies of transplanted irradiated bone
      marrow, or of bone marrow obtained from irradiated mice significantly before the
      appearance of leukaemia, have been interpreted as the chromosome 2 deletion being
      a high frequency, possibly initiating event. However, these studies had not
      specifically addressed the question of whether the characteristic deletion was
      induced at a high frequency in stem cells. Using a PCR-based technique, we have
      studied the induction of chromosome 2 LOH in the progeny of (CBA/H x C57BL/6)F1
      stem cells after a potentially leukaemogenic radiation exposure. Whilst
      chromosome 2 LOH can be induced directly by irradiation and there is a
      preferential loss of the CBA allele, the frequency is no greater than LOH induced
      in other chromosomal regions studied. The data do not support radiation-induced
      deletion involving one homologue of chromosome 2 in long-term repopulating stem
      cells (<1 in 200) being as high a frequency event as might be inferred by
      previous cytogenetic studies of total bone marrow.

PMID- 11587220
TI  - Examination of temporal trends in the incidence of childhood leukaemias and
      lymphomas provides aetiological clues.
AB  - The age-sex distributions and temporal trends in incidence of leukaemia and
      lymphoma from the Manchester Children's Tumour Registry (MCTR), 1954-1998, are
      reported. This 45-year study includes 1795 children, all of whom had a
      histologically and/or cytologically verified leukaemia or lymphoma. At the time
      of their diagnoses all the children were under 15 years of age and were resident
      in a geographically defined area of northwest England covered by the MCTR. Log
      linear modelling identified significant linear increases in acute lymphoblastic
      leukaemia (ALL) (average annual increase 0.7%; P= 0.005) and in Hodgkin's disease
      (HD) (1.2%, P=0.04), but not in acute myeloid leukaemia (AML), nor in non
      Hodgkin's lymphoma (NHL). The increase in ALL was most pronounced amongst males,
      aged 1-4 years, and is likely to be due to precursor B-cell leukaemias. The
      increases in ALL and HD are discussed in relation to current hypotheses
      suggesting a role for infection. Additionally, a non-linear cohort effect was
      identified for NHL (P= 0.008), which may indicate the involvement of
      environmental factors other than infection.

PMID- 11587221
TI  - CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by
      dendritic cells and cross-priming of CD8+ cytotoxic T cells.
AB  - C2B8 (Rituximab, MabThera) is a chimeric mouse/human monoclonal antibody (mAb)
      directed against the human B cell-restricted cell surface antigen CD20 which is
      used as an alternative medication in the treatment of B cell non-Hodgkin
      lymphomas (NHL). Treatment of CD20+ B cells with C2B8 triggers different cell
      damaging effects including complement-dependent lysis of tumor cells, antibody
      dependent cellular cytotoxicity and induction of apoptosis. Dendritic cells (DC)
      have recently been shown to ingest cell debris and to present associated antigens
      even on MHC class I molecules, a mechanism called cross-presentation. In this
      study, we investigated whether C2B8 treatment of lymphoma promotes the induction
      of CD8+ T cell responses against lymphoma cell-associated antigens via, cross
      presentation. We used Daudi lymphoma cells as a model system in our studies and
      could demonstrate, that C2B8-treated Daudi cells undergo apoptosis, are
      phagocytosed by DC and induce in DC typical features of maturation; among them,
      the induction of CD83 expression as well as the up-regulation of prominent
      accessory molecules (CD40, CD86) and MHC molecules. Importantly, upon co-culture
      of such lymphoma cell-pulsed DC with autologous T cells, we could induce
      efficient cytotoxic T cell (CTL) responses against Daudi cell-associated
      antigens. These findings suggest that antibody treatment of tumor cells can, in
      addition to its direct cell damaging effects, under certain conditions,
      contribute to an induction of potentially protective cytotoxic T cell responses.

PMID- 11587222
TI  - Chromosomal changes pattern and gene amplification in T cell non-Hodgkin's
      lymphomas.
AB  - T cell non-Hodgkin's lymphomas are a heterogeneous group of lymphomas with poor
      prognosis, and whose genetic alterations are not well understood. Comparative
      genomic hybridization (CGH) is a technique that allows the identification of DNA
      imbalances without cytogenetic studies. We have studied 37 samples from 29 T cell
      non-Hodgkin's lymphomas (25 peripheral and four lymphoblastic lymphomas) by CGH
      in order to detect DNA sequence copy number changes of putative importance in the
      biology and prognosis of these neoplasms. We detected abnormal CGH profiles in
      16/27 (59%) of samples at diagnosis, a ratio that increased to 66% (23/37) when
      we included the relapsed samples. The most common recurrent changes were gains
      related to the X chromosome, either the whole chromosome or partially the Xq26-27
      bands (19%). Other recurrent changes included gains of bands 9q34, gains of
      chromosomes 17, 19, and 20, and complete or partial deletions of chromosome 13
      (10%). Cancer-related genes located at Xq26-28 region were analyzed by Southern
      blot and fluorescence in situ hybridization (FISH). Low level amplification of
      some of these genes was detected by this technique confirming the results
      obtained by CGH in this region. The detection of abnormal CGH profiles in these T
      cell lymphomas could have clinical implications. Patients with abnormal CGH
      profiles showed significant associations with advanced stage of disease,
      overexpression of P53, and higher proliferative index.

PMID- 11587223
TI  - Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the x(c)-
      cystine transporter: a new action for an old drug.
AB  - Although cyst(e)ine is nutritionally a non-essential amino acid, lymphoid cells
      cannot synthesize it, rendering their growth dependent on uptake of cyst(e)ine
      from their microenvironment. Accordingly, we previously suggested that the x(c)-
      plasma membrane cystine transporter provided a target for lymphoid cancer
      therapy. Its inhibition could lead to cyst(e)ine deficiency in lymphoma cells via
      reduction of both their cystine uptake and cysteine supply by somatic cells. In
      this study, using rat Nb2 lymphoma cultures, drugs were screened for growth
      arrest based on x(c)- inhibition. Sulfasalazine was fortuitously found to be a
      novel, potent inhibitor of the x(c)- transporter. It showed high rat lymphoma
      growth-inhibitory and lytic activity in vitro (IC50 = 0.16 mM), based
      specifically on inhibition of x(c)--mediated cystine uptake, in contrast to its
      colonic metabolites, sulfapyridine and 5-aminosalicylic acid. Sulfasalazine was
      even more effective against human non-Hodgkin's lymphoma (DoHH2) cultures. In
      rats (n = 13), sulfasalazine (i.p.) markedly inhibited growth of well-developed,
      rapidly growing rat Nb2 lymphoma transplants without apparent side-effects.
      Reduced, macrophage-mediated supply of cysteine was probably involved. In five
      rats, 90-100% tumor growth suppression, relative to controls, was obtained. The
      x(c)- cystine transporter represents a novel target for sulfasalazine-like drugs
      with high potential for application in therapy of lymphoblastic and other
      malignancies dependent on extracellular cyst(e)ine.

PMID- 11587224
TI  - Characterization of two novel cell lines, DERL-2 (CD56+/CD3+/Tcry5+) and DERL-7
      (CD56+/CD3-/TCRgammadelta-), derived from a single patient with CD56+ non
      Hodgkin's lymphoma.
AB  - Two novel IL2-dependent cell lines, DERL-2 and DERL-7, were established from a
      patient with hepatosplenic gammadelta T cell lymphoma. This patient presented, at
      diagnosis, two discrete populations of CD56+ cells, one TCRgammadelta+, the
      second lacking T cell-restricted antigens. The cell lines derived displayed
      features corresponding to the two cellular components of the disease: DERL-2 was
      CD56+/CD3+/TcRgammadelta+ while DERL-7 was CD56+/CD3-/TcRgammadelta-. Along with
      CD56, the two cell lines shared the expression of CD7, CD2, CD158b and CD117.
      Karyotype analysis showed that both cell lines were near-diploid, with iso-7q and
      loss of one chromosome 10. In addition, DERL-2 showed 5q+ in all metaphases
      analyzed, while DERL-7 revealed loss of one chromosome 4. Genotypically, both
      cell lines shared the same STR pattern at nine loci and demonstrated an identical
      rearranged pattern of the T cell receptor genes beta, gamma and delta, with
      respect to the original tumor cells. These data indicated that both cell lines
      and the original neoplastic populations were T cell-derived and arose from a
      common ancestor. Among a large panel of cytokines tested, only SCF was able to
      substitute IL2 in supporting cell proliferation. Moreover, SCF and IL2 acted
      synergistically, dramatically enhancing cell growth. These cell lines may
      represent a model to further analyze the overlap area between T and NK cell
      malignancies, and may provide new information about the synergistic action of IL2
      and SCF on normal and neoplastic T/NK cells.

PMID- 11587225
TI  - TRAIL-induced eradication of primary tumour cells from multiple myeloma patient
      bone marrows is not related to TRAIL receptor expression or prior chemotherapy.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) shares significant homology with
      CD95 (Fas) ligand and has the ability to induce apoptosis in sensitive cells
      through a caspase-mediated pathway. We have evaluated the activity of purified
      human recombinant soluble TRAIL (S-TRAIL, comprising residues 114-281; Biomol,
      Plymouth Meeting, PA, USA) and a leucine zipper construct of TRAIL (LZ-TRAIL;
      Immunex, Seattle WA, USA) against myeloma cell lines NCI H929, U266, RPMI 8226,
      the FasL-sensitive Jurkat T cell ALL line, the lymphoblastoid cell line MC/CAR
      and primary tumour cells from 16 myeloma patients. Furthermore, we examined the
      relationship between TRAIL-induced apoptosis and TRAIL receptor expression
      utilising RT-PCR and flow cytometry. Two of three myeloma cell lines and Jurkat
      were TRAIL sensitive whereas MC/CAR was relatively resistant. Five of 16 (31%)
      primary tumours demonstrated > or =20% reduction in myeloma cells following TRAIL
      incubation (20-59%). This did not correlate with prior therapy. Four cell lines
      (two sensitive) and five primary tumours (two sensitive) demonstrated mRNA
      expression of the intra-cellular death domain containing TRAIL-R1. Variable
      expression of the two decoy (TRAIL-R3 and R4) and soluble (osteoprotegerin)
      receptors was seen and this did not correlate with TRAIL resistance. We conclude
      that myeloma cell expression of death effector receptors for TRAIL is
      insufficient to confer sensitivity to TRAIL-induced apoptosis but that in a
      significant minority of patients, irrespective of prior therapy, tumour cells are
      sensitive to TRAIL. The further investigation of TRAIL as an adjunct to presently
      available therapies for myeloma is justified.

PMID- 11587226
TI  - Rapid generation of a tetracycline-inducible BCR-ABL defective retrovirus using a
      single autoregulatory retroviral cassette.
AB  - The development of chronic myelogenous leukemia (CML) models in mice using an
      inducible BCR-ABL gene has been hampered by the requirement of sequential
      expression of tTA (Tet repressor-VP16 fusion protein) and Tet-OP sequences in the
      same cells after separate transfection. This double transfection strategy is time
      consuming as it requires screening of many hundreds of individual clones and
      cannot be applied to primary hematopoietic cells. To generate a tetracycline
      inducible BCR-ABL retrovirus, we have subcloned BCR-ABL p210 cDNA in the SIN
      Retro-TET vector, which allows regulated expression of a gene of interest in a
      single autoregulatory cassette, containing both tTA and Tet OP sequences.
      Retroviral particles were obtained by transfecting the SIN-BCR-ABL p210 construct
      into the 293 cells and by VSVG pseudotyping. To determine the functionality of
      the retrovirus, the IL-3-dependent murine Ba/F3 cell line was retrovirally
      transduced and clones were grown in the absence of both IL-3 (to select for
      transformed cells) and a tetracycline analog, doxycycline (to induce BCR-ABL
      expression). Using this technique, polyclonal Ba/F3 cells and several growth
      factor-independent Ba/F3 clones expressing BCR-ABL were obtained within 2-3
      weeks. A single dose of doxycycline added to the medium (1 microg/ml), induced in
      different clones, a reduction of BCR-ABL protein levels by 60-90% at 24 h,
      leading to cell death in the absence of IL-3. In several individual clones, BCR
      ABL expression was further reduced to become almost undetectable at 48 h. The
      doxycycline-regulated BCR-ABL expression was stable, as many clones maintained in
      culture for >8 months showed a persistent inhibitory response to doxycycline
      addition in the medium. In in vivo experiments, subcutaneous injection of 2 x
      10(6) Ba/F3-SIN p210 cells in nude mice induced visible tumors in 2 weeks and all
      established tumors completely regressed upon addition of doxycycline in the
      drinking water (200 microg/ml). To determine the functionality of the inducible
      BCR-ABL retrovirus in vivo, primary Lin- bone marrow cells were transduced with
      SIN-p210 and transplanted in lethally irradiated mice. All transplanted mice had
      successful hematopoietic reconstitution and BCR-ABL integration was found in the
      peripheral blood of seven out of 14 mice available for long-term analysis (>6
      months). However, despite evidence of retrovirus-mediated gene transfer, there
      was no evidence of leukemia, due either to low viral titers or to the relative
      inefficiency of the minimal CMV promoter in primary hematopoietic cells. Thus,
      these results demonstrate for the first time, to our knowledge, the feasibility
      to generate an inducible BCR-ABL retrovirus in a single step, in the context of
      an immortalized cell line. Our data suggest that with further improvements of the
      retrovirus-mediated gene transfer technology, it might be possible to generate
      inducible leukemia models in mice by the use of single retroviral constructs.

PMID- 11587227
TI  - P53 downregulation in myelodysplastic syndrome--a quantitative analysis by
      competitive RT-PCR.

PMID- 11587228
TI  - Successful treatment of acute promyelocytic leukemia in pregnancy with all-trans
      retinoic acid.

PMID- 11587229
TI  - Mechanism of action on B cell lymphoma by chimeric anti-CD20 monoclonal antibody.

PMID- 11587230
TI  - Acute myeloid leukemia in a patient with ataxia-telangiectasia: a case report and
      review of the literature.

PMID- 11587231
TI  - Successful treatment of Aspergillus spondylodiscitis with high-dose itraconazole
      in a patient with acute myelogenous leukemia.

PMID- 11587232
TI  - Detection of myeloperoxidase by flow cytometry in acute lymphoblastic leukaemias
      with BCR-ABL gene rearrangement.

PMID- 11587233
TI  - Minimally differentiated acute myeloid leukemia (AML-MO) with lymphoid
      presentation at relapse: a case report.

PMID- 11587234
TI  - MLL-AF6 fusion resulting from a new three-way translocation t(6;11;7) in a
      patient with acute myeloid leukemia.

PMID- 11587235
TI  - Profiles of patients who experienced a late acute rejection due to nonadherence
      with immunosuppressive therapy.
AB  - The purpose of this study was to determine the significance and patient profiles
      of nonadherence with immunosuppressive therapy in the etiology of late acute
      rejections (LARs), more than 1 year after heart transplantation. Nonadherence was
      assessed in 101 heart transplant recipients (14 females, 87 males) with a median
      age of 56 (Q1=50; Q3=61) and a median posttransplant status of 3 (range, 1-6)
      years, using electronic event monitoring and self-report. The influence of
      depression, perceived self-efficacy, knowledge, perceived health, symptom
      frequency and distress, perceived social support, and adherence with outpatient
      appointments on medication nonadherence was examined. Ten LARs occurring in six
      patients were observed. Nine of the rejections, emerging in five patients,
      appeared to be caused by medication nonadherence. Nonadherence with
      immunosuppressive therapy is a major risk factor in the etiology of LAR. Patient
      profiles allow the identification of patients at risk.

PMID- 11587236
TI  - Bystander cardiopulmonary resuscitation: would they do it again?
AB  - During the last three decades, community education programs have been initiated
      with the purpose of teaching community citizens cardiopulmonary resuscitation
      (CPR). Millions of people have learned the technique. However, the frequency of
      bystander initiated CPR prior to emergency medicine service (EMS) arrival is
      still very low. This can lead one to ask if CPR training is optimal. Perhaps
      motivational aspects and psychological inhibitors to starting CPR should be
      included in CPR training. So far, CPR training has been skills oriented and has
      assumed that a bystander competent in CPR will intervene when required. However,
      this does not seem to be the case, as there are indications in recent research,
      for example, that the will to help and the courage to intervene are also needed.
      Bystanders who intervene in a cardiac arrest event improve the victim's chance of
      survival. However, there is little knowledge regarding the rescuers' reactions
      concerning their performance and whether they will overcome the trauma of the
      event and be prepared to do it again.

PMID- 11587237
TI  - To be resuscitated or not: the concepts in decision making.
AB  - The aim of this article is to provide an overview of the available scientific
      evidence to support decisions to withhold cardiopulmonary resuscitation in
      hospitals. The decision to perform resuscitation or not is a complex one that
      requires consideration of a number of factors, including patient preference and
      patient clinical status. The three fundamental questions that must be answered in
      making an informed decision about whether to attempt resuscitation are discussed
      and the evidence used to answer them is presented.

PMID- 11587238
TI  - The measurement of health-related quality of life in patients with coronary heart
      disease.
AB  - This article provides an overview of the key concepts and methodological issues
      in the measurement of health-related quality of life in patients with coronary
      heart disease. It then outlines the approach adopted in a British study to
      develop and test a new disease-specific health-related quality of life instrument
      for use with individuals with myocardial infarction.

PMID- 11587239
TI  - Coping in spouses of patients with acute myocardial infarction in the early phase
      of recovery.
AB  - The purpose of this study was (1) to determine the coping strategies employed by
      spouses of patients with AMI in the early phase of the crisis, (2) to define the
      role of age, gender, health perception, time since infarction, spouses' fears,
      and negative life events in the choice of coping strategies applied, and (3) to
      test the effect of coping strategies on physical and psychological strain. Fifty
      seven spouses participated in the study, 47 were female and 10 were male. Data
      were collected by structured questionnaires, which were distributed to the
      spouses from 2 weeks-4 months after the patient's AMI. The researchers found that
      age, negative life event during the last 12 months, time since infarction, and
      the spouse's fears influenced the choice of strategies. In the early stage of the
      crisis, positive reappraisal seems to be a strategy that increased physical
      strain. Spouses' need for social support in the early stage of the crisis is a
      factor for health care providers to bear in mind. Besides giving information,
      empathy, and understanding, health care personnel can try to assist spouses in
      their efforts to reappraise their situation.

PMID- 11587240
TI  - The clinical implications of cognitive impairment in elderly patients with
      chronic heart failure.
AB  - The purpose of this study was to examine whether cognitive dysfunction was
      associated with poor participation in an outpatient treatment program for
      patients with chronic heart failure and if it was related to specific patient
      characteristics. Cognitive function was measured with the Mini Mental State
      Examination (MMSE). Twenty-three of 78 (29%) patients randomized to structured
      care did not participate in this program and nonparticipation during 6-month
      follow-up was associated with an MMSE score below the median and a low calculated
      creatinine clearance (CrCl) (R2=0.15, p=0.0025) at entry. In the entire group
      long duration of heart failure and low blood hemoglobin concentration were
      independently associated with an MMSE score below the median at entry (R2=0.14, p
      < 0.0001). Among elderly patients hospitalized with moderate-severe chronic heart
      failure, judged to be eligible for a nurse-directed outpatient program after
      discharge, a low MMSE score predicted nonparticipation in such a program.
      Cognitive dysfunction, which was related to the duration of heart failure, should
      be evaluated in the treatment of patients with chronic heart failure.

PMID- 11587241
TI  - Addressing the burden of heart failure in Australia: the scope for home-based
      interventions.
AB  - The growing burden of heart failure (HF) challenges health practitioners to
      implement and evaluate models of care to facilitate optimal health related
      outcomes. Australia supports a publicly funded universal health insurance system
      with a strong emphasis on primary care provided by general practitioners. The
      burden of chronic HF, and a social and political framework favoring community
      based, noninstitutionalized care, represents an ideal environment in which home
      based HF programs can be implemented successfully. Cardiovascular nurses are well
      positioned to champion and mentor implementation of evidence-based, patient
      centered programs in Australian communities. This paper describes the
      facilitators and barriers to implementation of best practice models in the
      Australian context. These include the challenge of providing care in a diverse,
      multicultural society and the need for clinical governance structures to ensure
      equal access to the most effective models of care.

PMID- 11587242
TI  - Research in cardiovascular nursing in Europe: toward a UNITED approach.
      Undertaking Nursing Interventions Throughout Europe Research Group.
AB  - This article describes the efforts of a recent initiative of the Working Group on
      Cardiovascular Nursing of the European Society of Cardiology. The Undertaking
      Nursing Interventions Throughout Europe (UNITE) Research Group represents a truly
      international team of nurses who collaborate on a number of research studies. The
      major focus of the group is to provide better care to patients in whom modern day
      treatment has proven to be ineffectual such as patients with chronic, intractable
      angina.

PMID- 11587243
TI  - Vanilloid receptor ligands: hopes and realities for the future.
AB  - Neurons possessing C-fibers transmit nociceptive information into the central
      nervous system and participate in various reflex responses. These neurons carry
      receptors that bind capsaicin, recently identified as the vanilloid VR1 receptor.
      Excitation of these cells by capsaicin is followed by a lasting refractory state,
      termed desensitisation, in which the neurons fail to respond to a variety of
      noxious stimuli. Desensitisation to capsaicin has a clear therapeutic potential
      in relieving neuropathic pain and ameliorating urinary bladder overactivity, just
      to cite 2 important examples. Vanilloids may also be beneficial in the treatment
      of benign prostate hyperplasia (BPH). Since the majority of elderly patients have
      neuropathic pain co-existent with urinary incontinence and/or BPH, a drug that
      ameliorates pain and improves urinary symptoms at the same time promises to be of
      great clinical value in geriatric medicine. In fact, capsaicin has already been
      shown to have a role in the treatment of conditions that can arise in the
      elderly, including herpes zoster-related neuropathic pain, diabetic neuropathy,
      postmastectomy pain, uraemic itching associated with renal failure, and urinary
      incontinence. The potent VR1 agonist resiniferatoxin, now in phase II clinical
      trials, appears to be superior to capsaicin in terms of its tolerability profile.
      Recent discoveries enhance the therapeutic potential of vanilloids. The
      recognition that VR1 also functions as a principal receptor for protons and
      eicosanoids implies that VR1 antagonists may be of value in the treatment of
      inflammatory hyperalgesia and pain. Animal experimentation has already lent
      support to this assumption. The discovery of VR1-expressing cells in the brain as
      well as in non-neural tissues such as the kidney and urothelium places VR1 in a
      much broader perspective than peripheral pain perception, and is hoped to
      identify further, yet unsuspected, indications for vanilloid therapy. The
      realisation that VR1 and cannabinoid CB1 receptors have overlapping ligand
      recognition properties may also have far-reaching implications for vanilloid
      therapy. In fact, arvanil, a combined agonist of VR1 and CB1 receptors, has
      already proved to be a powerful analgesic drug in the mouse. From academic
      molecular biology laboratories to industrial drug discovery centres to the
      clinics, there is a steady flow of new data, forcing us to constantly revise the
      ways we are thinking about vanilloid receptor ligands and their hopes and
      realities for the future. This review covers the most promising current trends in
      vanilloid research with special emphasis on geriatric medicine.

PMID- 11587244
TI  - Drug treatment of the complications of cirrhosis in the older adult.
AB  - Several age-related changes occur in the structure and functions of the liver.
      The volume of the liver decreases, despite an increase in the size of
      hepatocytes, suggesting loss of liver cells. There are decreases in hepatic blood
      flow, the synthesis of urea and cholesterol, and the metabolism of drugs.
      Moreover, the regenerative capacity of liver becomes less efficient. Certain
      caveats are important when treating older patients with liver disease. Strict
      dietary restrictions, such as a low protein diet, should be avoided in the
      elderly (unless the patient is encephalopathic) because these patients are often
      undernourished to start with. Similarly, strict salt restriction should be
      enforced with caution, since it makes food less palatable and may take away what
      little desire such patients have to eat. Diuretic doses should be adjusted
      carefully because of greater risks of azotaemia and electrolyte disturbances in
      the elderly. Extra vigilance should be exercised in the early detection of
      infections that are more likely to occur in patients with cirrhosis. For example,
      spontaneous bacterial peritonitis can be missed in the elderly because of poor
      systemic (fever, abdominal tenderness) and laboratory responses (leucocytosis).
      In patients presenting with acute variceal bleeding, it is better to err on the
      side of underhydration than overhydration because of the risk of congestive heart
      failure. Vasopressin should be avoided in the elderly, since this drug has a high
      probability of precipitating an ischaemic event. Older patients do not tolerate
      beta-blockers as well as younger individuals and may require other treatment
      strategies for the prevention of variceal rebleeding episodes. Hepatic
      encephalopathy, especially the milder form, needs careful assessment because it
      can be easily confused with senile dementia syndromes. Cirrhosis is a
      premalignant condition and patients are at increased risk of developing
      hepatocellular carcinoma (HCC), a tumour seen predominantly in the elderly. All
      patients with cirrhosis should be maintained on a lifelong screening programme
      consisting of a 6-monthly assessment of alpha-fetoprotein and an imaging study,
      since early detection provides the only hope for cure of HCC. The only definitive
      treatment of cirrhosis is liver transplantation. Advanced age is not a
      contraindication to transplantation, and survival in older patients (aged >60
      years) is comparable to that in younger individuals.

PMID- 11587245
TI  - Use of reperfusion therapies in elderly patients with acute myocardial
      infarction.
AB  - Almost one-third of patients with acute myocardial infarction (AMI) are aged >75
      years, and this proportion is expected to increase as the population ages.
      Mortality and complication rates are particularly high in the elderly, yet
      reperfusion therapies, including thrombolysis and primary percutaneous
      transluminal coronary angioplasty (PTCA), are under-utilised among eligible
      patients. There is a concern, whether real or perceived, that the risks of such
      therapies may outweigh the potential benefits. Presently, there are no randomised
      clinical trials of thrombolytic therapy in the elderly that definitively assess
      its efficacy in patients aged >75 years. In the meta-analysis of randomised
      trials by the Fibrinolytic Therapy Trialists, thrombolysis was associated with a
      mortality reduction among patients aged >75 years, though this reduction did not
      meet formal statistical significance. Because the point estimates for mortality
      reduction were in the direction that favoured use of thrombolytic therapy, the
      American Heart Association/American College of Cardiology AMI guidelines
      recommend thrombolysis as a Class 2a therapy in this age group. Observational
      studies using data from the Cooperative Cardiovascular Project database and the
      National Registry of Myocardial Infarction have recently cast some doubt on the
      benefit of thrombolysis among the elderly, but definitive answers from a
      randomised trial are still lacking. Meanwhile, primary PTCA, which has been
      compared to thrombolysis in both trial and observational settings, appears to
      offer the mortality benefit of reperfusion with lower stroke rates. Since primary
      PTCA is not widely available, efforts must be made to maximise available
      therapies in the elderly. Early diagnosis is essential, as is prompt reperfusion
      among eligible patients, since delay is so strongly associated with mortality
      with both thrombolysis and PTCA. Finally, newer, more fibrin-specific
      thrombolytics may decrease the bleeding risk associated with thrombolytic
      therapy.

PMID- 11587246
TI  - Hot flashes: aetiology and management.
AB  - Menopause, an event often accompanied by symptoms such as hot flashes, can have a
      significant impact on a woman's quality of life. A majority of women will
      experience hot flashes at some point in their life, given a normal life span.
      Despite multiple theories, the exact pathophysiology of hot flashes is not yet
      known. Many types of treatment options exist for women with hot flashes, from
      hormonal and nonhormonal pharmacological therapies to nonpharmacological
      interventions. Choosing the best treatment option for specific women involves
      knowledge of the risks and benefits of each treatment. Hormones (estrogen and/or
      progesterone, or tibolone alone) are still the most effective option available,
      resulting in an 80 to 90% reduction in hot flashes. The best nonhormonal
      treatment to date is in the class of newer antidepressants that comprises various
      selective reuptake inhibitors; for example, venlafaxine provides about a 60%
      reduction in hot flashes. This article provides evidence-based information about
      available treatment options for hot flash management, with special consideration
      of populations such as breast cancer survivors.

PMID- 11587247
TI  - Age-related changes in wound healing.
AB  - Evidence for age-related effects on wound healing have been derived for the most
      part from empirical observations without adjustment for confounders other than
      age. Age-related changes in the structure and function of the skin do occur. Some
      of these changes result from chronic solar radiation exposure rather than
      chronological age per se. The tensile strength of wounds, accumulation of wound
      healing factors and rate of wound closure have all been examined in relation to
      chronological aging. However, the clinical impact of these changes in acute wound
      healing appears to be small. Poor healing in chronic wounds is more often related
      to comorbid conditions rather than age alone. Since the majority of these chronic
      wounds occur in elderly populations, this has contributed to the conclusion that
      aging itself may influence healing. Progress in understanding the role that
      growth factors play in wound healing and the ability to synthesise adequate
      quantities of these factors for clinical use has led to clinical trials
      evaluating their use in wound healing. The results of these studies, with the
      possible exception of those in diabetic wounds, have been disappointing. Insight
      into the wound healing process indicates that growth factors interact during
      wound healing in a sequential and orderly process. Improved wound healing may
      require different clinical designs or the use of these factors in a precisely
      timed sequential administration.

PMID- 11587248
TI  - The tolerability of lamotrigine in elderly patients with epilepsy.
AB  - OBJECTIVE: To determine the tolerability of lamotrigine in elderly patients with
      epilepsy. DESIGN: Pooled data from 13 lamotrigine clinical trials. SETTING:
      Multicentre clinical trials conducted in primary care and neurology practices.
      PARTICIPANTS: 208 elderly patients (aged > or = 65 years) were identified: 146
      lamotrigine-treated patients, 53 carbamazepine-treated patients and 9 phenytoin
      treated patients. INTERVENTIONS: Extent of exposure, incidence of drug-related
      adverse events, serious adverse events and study withdrawals were examined.
      RESULTS: The median duration of exposure for lamotrigine monotherapy and add-on
      therapy was 24.1 and 47.4 weeks, respectively. The median daily dosage of
      lamotrigine was 100 mg for monotherapy (range 75 to 500 mg) and 300 mg for add-on
      therapy (range 25 to 700 mg). Overall, the incidence of drug-related adverse
      events was lower for lamotrigine than comparator drugs: 49% (72/146) for
      lamotrigine compared with 72% (38/53) for carbamazepine (p = 0.006), and 89%
      (8/9) for phenytoin (p = 0.035) although patient numbers in each treatment group
      were not comparable. Patients receiving lamotrigine reported incidences of
      somnolence (p = 0.012), rash (p = 0.034), and headache (nonsignificant) that were
      one-half the incidence reported with carbamazepine monotherapy. Rash was the most
      common reason for study withdrawal: 4% (6/146) lamotrigine, 17% (9/53)
      carbamazepine and 0% phenytoin. Seven (5%, 7/146) lamotrigine-treated patients, 4
      (8%, 4/53) carbamazepine-treated patients and 1 (11%, 1/9) phenytoin-treated
      patient experienced drug-related serious adverse events. CONCLUSION: Lamotrigine,
      used in the currently prescribed adult dosage regimen, was well tolerated in
      elderly patients with epilepsy.

PMID- 11587249
TI  - Vitamin D deficiency and multicultural Australia.

PMID- 11587250
TI  - Evolving evidence and continuing uncertainties for eating disorders.

PMID- 11587251
TI  - Preventing osteoporosis naturally.

PMID- 11587252
TI  - Trials on trial.

PMID- 11587253
TI  - An open, crossover trial of calcium-fortified milk in prevention of early
      postmenopausal bone loss.
AB  - OBJECTIVE: To establish whether calcium-enriched milk reduces bone loss in women
      who are within five years of the menopause and have a basal calcium intake < or =
      1,250 mg. DESIGN: Two-year open, crossover study. SETTING: A community-based
      study carried out in Adelaide, South Australia, between September 1997 and June
      2000. PARTICIPANTS: 115 women recruited by newspaper advertisement, who were less
      than five years postmenopausal, were not taking hormone or other therapy that
      could affect bone and had a usual calcium intake < or = 1,250 mg daily.
      INTERVENTION: Participants were randomly allocated to Group 1 (who received a
      supplement of 3 L of calcium-fortified milk weekly in the first year) or Group 2
      (who followed their usual diets in the first year). In the second year, Group 1
      reverted to their usual diets, and Group 2 received the milk supplement. MAIN
      OUTCOME MEASURES: Difference in loss of bone mineral density (BMD) at the spine
      and forearm in the same individuals on and off the milk supplement; urinary
      excretion of bone resorption markers in a subset of 72 participants in the first
      year. RESULTS: With each woman serving as her own control, the rate of bone loss
      from the spine was 1.76 percentage points less when the women were taking the
      milk supplement than when they were on their usual diet (95% CI, 0.54%-2.98%;
      P=0.006). However, there was no significant difference in bone loss in the
      forearm. Fasting urine levels of two markers of bone resorption (hydroxyproline
      and deoxypyridinoline) were significantly lower in 36 women in the milk group
      than in 36 women in the usual-diet group (P=0.03 for both markers). CONCLUSION:
      Supplementing the diet with calcium-fortified milk early in the postmenopausal
      period delays bone loss at the spine but not at the forearm, and reduces the
      excretion of bone resorption markers.

PMID- 11587254
TI  - High prevalence of coeliac disease in a population-based study from Western
      Australia: a case for screening?
AB  - OBJECTIVES: To determine the prevalence of coeliac disease in an Australian rural
      community. DESIGN: Retrospective analysis of stored serum samples from 3,011
      random subjects from the Busselton Health Study. IgA antiendomysial antibodies
      (AEA) were detected by indirect immunofluorescence, and subjects testing positive
      were contacted and offered small-bowel biopsy. MAIN OUTCOME MEASURES: Prevalence
      of AEA positivity and biopsy-proven coeliac disease in the community with
      reference to the proportion of symptomatic to asymptomatic patients. RESULTS: 10
      of 3,011 subjects were AEA positive. One subject had died, one subject could not
      be traced and one refused small-bowel biopsy. All subjects with detectable AEA
      who consented to biopsy had pathological changes consistent with coeliac disease.
      The prevalence of newly diagnosed biopsyproven coeliac disease is 7 in 3,011 (1
      in 430). Two further subjects had a diagnosis of coeliac disease before this
      study. When all AEA-positive patients and those previously diagnosed are
      included, the prevalence is 12/3,011 (1 in 251). There was a significant
      clustering of cases in the 30-50-years age range, with 10/12 (83%; 95% CI, 52%
      98%) aged between 30 and 50 years, compared with 1,092/3,011 (36%; 95% CI, 35%
      38%) of the total population (P<0.03). Of the eight AEA-positive subjects who
      could be contacted, four had symptoms consistent with coeliac disease and four
      were asymptomatic. Three subjects were iron-deficient, four subjects had first
      degree relatives with coeliac disease and one subject had type 1 diabetes
      mellitus. CONCLUSIONS: The prevalence of coeliac disease is high in a rural
      Australian community. Most patients are undiagnosed, and asymptomatic.

PMID- 11587255
TI  - Vitamin D deficiency in veiled or dark-skinned pregnant women.
AB  - OBJECTIVES: To determine the vitamin D status of veiled or dark-skinned pregnant
      women, because of their known increased risk of vitamin D deficiency. DESIGN: An
      audit of vitamin D status. SETTING: An antenatal clinic in a major metropolitan
      teaching hospital, Melbourne, Victoria. PARTICIPANTS: Pregnant women attending
      the clinic who agreed to be screened. MAIN OUTCOME MEASURES: Serum 25
      hydroxyvitamin D3 (25OHD3) level at first visit to the antenatal clinic. RESULTS:
      Of 94 women, 82 were screened. Sixty-six women (80%) had 25OHD3 values below the
      test reference range (22.5-93.8 nmol/L). CONCLUSIONS: Our findings are a cause
      for concern, because vitamin D deficient women are at risk of bone disease and
      their children at risk of neonatal hypocalcaemia and rickets.

PMID- 11587256
TI  - Vitamin D deficiency in mothers of infants with rickets.
AB  - OBJECTIVE: To identify infants treated for vitamin D deficiency rickets, and to
      determine the incidence of vitamin D deficiency in their mothers and their
      mothers' country of origin. DESIGN: A retrospective audit of the medical records
      of children diagnosed with vitamin D deficiency rickets. Inpatients were
      identified by discharge diagnoses of vitamin D deficiency or hypocalcaemia and
      outpatients by pharmacy dispensing of cholecalciferol. SETTING: The Women's and
      Children's Health Care Network and the Southern Health Care Network (Melbourne,
      VIC) from June 1994 to February 1999. PATIENTS: 55 children with vitamin D
      deficiency rickets. RESULTS: Fifty-four of the 55 children were born to mothers
      with ethnocultural risk factors for vitamin D deficiency. Vitamin D status had
      been assessed in 31 of the 55 mothers (56%): 25 (81%) had 25-hydroxyvitamin D3
      concentrations < or = 25 nmol/L, consistent with osteomalacia. CONCLUSION:
      Vitamin D deficiency continues to occur in children of migrant families. When
      infants are diagnosed with vitamin D deficiency, vitamin D levels in their
      mothers and siblings should also be assessed.

PMID- 11587257
TI  - Contaminated medication precipitating hypoglycaemia.
AB  - We report a case of hypoglycaemia in a patient with diet-controlled type 2
      diabetes. Enquiries and investigations led to a diagnosis of sulfonylurea
      poisoning from contaminated herbal medication.

PMID- 11587259
TI  - Risk of death from methicillin-resistant Staphylococcus aureus bacteraemia: a
      meta-analysis.
AB  - OBJECTIVE: To estimate the risk of death from healthcare-associated (nosocomial)
      bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA), and
      compare it with that of nosocomial bacteraemia caused by methicillin-sensitive S.
      aureus (MSSA), by meta-analysis of selected studies. DATA SOURCES: Medline,
      EMBASE, Current Contents and Cochrane Library were searched for the period
      January 1978 (or earliest date of the database, if later than 1978) to December
      2000. STUDY SELECTION: Studies which compared mortality of nosocomial MRSA and
      MSSA bacteraemia. DATA SYNTHESIS: Nine studies were analysed. All but one found
      an increased relative risk (RR) of death from MRSA bacteraemia, with RR ranging
      from 0.89 to 4.94. Meta-analysis showed that patients with MRSA bacteraemia have
      an RR of death, compared with patients with MSSA bacteraemia, of 2.12 (95% CI,
      1.76-2.57) using the fixed-effect method, and 2.03 (95% CI, 1.55-2.65) using the
      random-effect method. CONCLUSION: MRSA bacteraemia is associated with a real
      increase in risk of death, further justifying ongoing MRSA surveillance and
      control in healthcare facilities.

PMID- 11587258
TI  - Anticoagulation in pregnancy and the puerperium.
AB  - For the management of acute thrombotic events in pregnancy therapeutic doses of
      low molecular weight heparins (LMWH) may be used, unless the shorter half-life of
      intravenous unfractionated heparin (UH) and predictable reversibility by
      protamine are important. Treatment should be continued up until delivery and into
      the puerperium. Pregnant women who have had an acute thrombotic event should be
      delivered by a specialist team. In the case of recent thrombosis, delivery should
      be planned and the time during which anticoagulation therapy is ceased around the
      time of delivery should be minimised. Therapeutic doses of LMWH contraindicate
      the use of regional anaesthesia, and a switch to intravenous UH before delivery
      may allow greater flexibility in this regard. Prophylactic doses of LMWH can be
      used to reduce the risk of recurrent thromboembolic events in pregnancy. The
      regimen used will depend on the previous history, the family history and the
      presence of risk factors, including the genetic and acquired causes of
      thrombophilia. Women with mechanical heart valves are at high risk during
      pregnancy and require therapeutic anticoagulation throughout pregnancy under the
      direction of experienced specialists. Low-dose aspirin can reduce the risk of
      recurrent pre-eclampsia by about 15%, but the role of UH and LMWH in the
      prevention of recurrent miscarriage or obstetric complications associated with
      uteroplacental insufficiency is still uncertain.

PMID- 11587260
TI  - Not-so-simple Simon.

PMID- 11587261
TI  - Hydrofluoric acid burn from a household rust remover.

PMID- 11587262
TI  - Randomised controlled trials: elements of a good study.

PMID- 11587263
TI  - Can ACE inhibitor therapy prevent end-stage renal failure?

PMID- 11587264
TI  - Cancer and the nervous system.
AB  - Brain tumours should be considered when patients present with headache with
      diurnal variation, seizures, or progressive neurological symptoms. Spinal cord
      compression by tumour is a medical emergency. Prognosis for patients with glioma
      is better in those with tumours of low grade, and in patients younger than 50
      years and with higher functional levels. Surgery, radiotherapy and chemotherapy
      can improve survival for patients. Anticancer therapies can have neurotoxic side
      effects.

PMID- 11587265
TI  - As work hours fall, medical school places must increase.

PMID- 11587266
TI  - The consultants' perspective.

PMID- 11587267
TI  - Cultural  change is required.

PMID- 11587268
TI  - A thorough review of part-time training is long overdue.

PMID- 11587269
TI  - Retrospective ethical approval.

PMID- 11587270
TI  - Time to move beyond clinical practice guidelines?

PMID- 11587271
TI  - Time to move beyond clinical practice guidelines?

PMID- 11587272
TI  - Adult living donor liver transplantation: another Pandora's box?

PMID- 11587273
TI  - Clinical classification systems for evaluating Indigenous perinatal and infant
      deaths.

PMID- 11587274
TI  - Connexin 26 mutations: the first practical genetic marker of inherited hearing
      loss.

PMID- 11587275
TI  - Professional development and ethics for today's and tomorrow's doctors.

PMID- 11587276
TI  - Perinatal and postneonatal mortality among Indigenous and non-Indigenous infants
      born in Western Australia, 1980-1998.
AB  - OBJECTIVE: To describe cause-specific perinatal and postneonatal mortality for
      Indigenous and non-Indigenous infants using a new classification system. DESIGN:
      Total population retrospective cohort study. PARTICIPANTS AND SETTING: All
      registered births in Western Australia of birthweight greater than 399 g from
      1980 to 1998, inclusive. MAIN OUTCOME MEASURES: Rates and time trends for all
      births 1980-1998, and cause-specific rates for births 1980-1993 of fetal,
      neonatal and postneonatal mortality among Indigenous and non-indigenous infants,
      using a classification system designed for use in perinatal, postneonatal and
      childhood deaths. RESULTS: For Indigenous infants born 1980-1998, the mortality
      rate before the first birthday was 2.7 times (95% CI, 2.5-2.9 times) that for non
      Indigenous infants. Indigenous infants born 1980-1993 had a higher mortality rate
      in all cause-of-death categories. The highest relative risk was for deaths
      attributable to infection (8.1; 95% CI, 6.5-10.0) which occurred primarily in the
      postneonatal period; the source of the infection was less likely to be identified
      in Indigenous deaths. From 1980-1998, the rate of neonatal deaths decreased at a
      greater rate for Indigenous than for non-Indigenous infants. However, while
      stillbirth and sudden infant death syndrome rates for non-Indigenous births fell,
      they remained static for Indigenous births. CONCLUSIONS: The new classification
      system, which considers the underlying rather than immediate cause of death,
      enables investigation of the causes of all deaths, from stillbirths to childhood.
      This system has highlighted the comparative importance of infection as a cause of
      death for Indigenous infants, particularly in the postneonatal period.

PMID- 11587277
TI  - Prevalence and nature of connexin 26 mutations in children with non-syndromic
      deafness.
AB  - OBJECTIVE: To determine (1) the prevalence and nature of connexin 26 mutations in
      a cohort of Australian children with non-syndromic hearing loss, and (2) the
      carrier frequency of the common connexin 26 mutation (35delG) in the general
      population. DESIGN: A cohort, case-finding study. Mutation analysis was performed
      on DNA extracted from white blood cells, buccal cells, or Guthrie blood spots.
      SETTING: A hearing loss investigation clinic and a deafness centre in two
      Australian capital cities, 1 January 1998 to 31 October 2000. PARTICIPANTS: (1)
      243 children (age range, 4 weeks to 16 years; median, 4 years), attending hearing
      loss clinics in Sydney and Melbourne; (2) 1000 blood samples obtained from
      anonymous Guthrie card blood spots collected in 1984 [corrected] by the Victorian
      Clinical Genetics Service as part of the newborn screening program. MAIN OUTCOME
      MEASURES: (1) The prevalence and types of connexin 26 mutations in a cohort of
      children with prelingual deafness; (2) the carrier frequency of the common
      connexin 26 mutation, 35delG, in the general population. RESULTS: Connexin 26
      mutations were identified and characterised in 52 (21%) of the 243 children; 14
      different mutations, including four previously unreported mutations (135S, C53R,
      T123N and R127C), were identified. The common 35delG mutation was found in 56 of
      the 104 alleles (ie, 86 of the connexin 26 alleles in which a mutation was
      positively identified). The mutations V371 and M34T were also relatively common.
      The carrier frequency of connexin 26 mutations and of the common 35delG connexin
      26 mutation in the Victorian population was estimated to be 1 in 54 and 1 in 100,
      respectively. CONCLUSIONS: Mutations in the connexin 26 gene (especially the
      35delG mutation) are a common cause of prelingual hearing loss in Australia.

PMID- 11587278
TI  - Effect of dietary restriction on participation in faecal occult blood test
      screening for colorectal cancer.
AB  - OBJECTIVES: To determine if participation in colorectal cancer screening using
      faecal occult blood testing (FOBT) is affected by a restrictive diet and if it is
      associated with certain demographic variables. PARTICIPANTS AND SETTING: 1,203
      residents of South Australia aged 50-69 years, with no "currently active bowel
      disease", randomly selected from a database of people willing to be contacted
      about unspecified health issues. DESIGN: Randomised controlled trial:
      participants were offered screening by immunochemical FOBT by mail in 1998. Half
      were randomly allocated to a group instructed to follow a low-peroxidase diet, as
      required for guaiac FOBT, while the other group was not so restricted. MAIN
      OUTCOME MEASURES: Effect of diet restriction on participation (return of
      correctly completed FOBT sample cards within 15 weeks); time taken to return
      cards; relationships between participation and demographic variables. RESULTS:
      Participation rates were 65.9% (no-diet group) and 53.3% (diet group)
      (difference, 12.6%; 95% CI, 7.1%-18.1%). In the first week, rates of return as a
      proportion of all tests returned were 13.1% (no-diet) and 1.6% (diet)
      (difference, 11.5%; 95% CI, 8.6%-14.4%), increasing to 54.3% and 44.5%,
      respectively, after five weeks (difference, 9.8%; 95% CI, 4.2%-15.4%).
      Participation was significantly associated with older age (odds ratio, 1.40; 95%
      CI, 1.10-1.78), but not sex, Index of Social Disadvantage or rural versus urban
      address. CONCLUSIONS: Dietary restrictions create a barrier to FOBT-based
      screening for colorectal cancer. The use of immunochemical rather than guaiac
      FOBT removes this barrier.

PMID- 11587279
TI  - The physical, sexual and emotional violence history of middle-aged women: a
      community-based prevalence study.
AB  - OBJECTIVES: To determine current and lifetime rates of the experience of partner
      abuse and sexual violence in a community-based sample of middle-aged women and
      compare these to figures obtained in a general practice setting. DESIGN AND
      METHODS: This research was part of the Melbourne Women's Midlife Health Project
      (MWMHP), an observational, longitudinal, population-based study of 438 Australian
      born women conducted over nine years. In 1996, during the sixth year of the
      study, we asked the MWMHP participants to complete a self-administered "violence
      questionnaire", incorporating a modified Conflict Tactics Scale and questions on
      sexual abuse experienced during childhood and adult life. RESULTS: Of the 395
      women remaining in the sixth year of follow-up of the MWMHP, 362 (92%) completed
      the questionnaire. Overall, 28.5% (n = 101) of the women had experienced some
      form of domestic violence (physical, sexual or emotional) during their lifetime;
      5.5% (n = 15) of women had experienced severe physical abuse in the past year at
      the hands of a partner; and 11.8% (n = 42) of the women had experienced rape or
      attempted rape between the age of 16 and the time of our survey. Regarding abuse
      in childhood, 8.9% (n = 32) of women had experienced physical abuse, 42.3% (n =
      152) had experienced non-contact sexual abuse, and 35.7% (n = 128) contact sexual
      abuse. Compared with the general-practice-based study, rates of childhood
      physical abuse and penetrative sexual abuse were similar, but rates of less
      intrusive child sexual abuse were significantly higher in our study. CONCLUSIONS:
      Doctors in all areas of medicine who are dealing with middle-aged women need to
      be aware of the levels of violence sustained by women throughout their lives.
      Such experiences may have a substantial impact on women's physical and mental
      wellbeing.

PMID- 11587280
TI  - Adult-to-adult living donor liver transplantation for fulminant hepatic failure.
AB  - The outcome of fulminant hepatic failure without timely liver transplantation is
      poor. We describe a 19-year-old woman with fulminant hepatic failure due to acute
      hepatitis B infection who received a living donor liver transplant from her
      sister. The donor's recovery was uneventful, allowing hospital discharge on Day
      6. Two months after transplantation the recipient developed a biliary stricture
      requiring surgery. One year after transplantation, her liver function was normal.

PMID- 11587281
TI  - An ethics core curriculum for Australasian medical Schools.
AB  - Teaching ethics incorporates teaching of knowledge as well as skills and
      attitudes. Each of these requires different teaching and assessment methods. A
      core curriculum of ethics knowledge must address both the foundations of ethics
      and specific ethical topics. Ethical skills teaching focuses on the development
      of ethical awareness, moral reasoning, communication and collaborative action
      skills. Attitudes that are important for medical students to develop include
      honesty, integrity and trustworthiness, empathy and compassion, respect, and
      responsibility, as well as critical self-appraisal and commitment to lifelong
      education.

PMID- 11587282
TI  - Is there a future for clinical ethics services in Australia?
AB  - Clinical ethics refers to the consideration of ethical issues arising directly in
      the context of patient care. Health professionals are generally adept at
      effectively and sensitively managing ethical issues in clinical care. However, in
      some settings, multidisciplinary clinical ethics services may enhance clinical
      practice by assisting clinicians, patients and others to identify, understand and
      manage ethical issues. Clinical ethics services may be particularly valuable for
      situations in which moral perspectives diverge or communication has deteriorated.
      Such services may facilitate discussion and help the parties find mutually
      satisfactory solutions. Clinical ethics services may take various forms,
      including clinical ethics committees, ethics consultants, patient advocates or
      other mechanisms for responding to complaints and grievances. There is
      considerable disagreement about key aspects of clinical ethics services,
      including who should conduct them, how they should be run and what role they
      should play in decision-making.

PMID- 11587283
TI  - COX-2 inhibition and thrombotic tendency: a need for surveillance.
AB  - Cyclooxygenase-2 (COX-2) inhibitors belong to a new class of drugs which have
      anti-inflammatory efficacy similar to that of traditional non-steroidal anti
      inflammatory drugs (NSAIDs), but are associated with a reduced incidence of
      adverse upper gastrointestinal events. Biochemical evidence that COX-2 inhibitors
      could promote or exacerbate a tendency to thrombosis is supported by recent
      results from clinical trials and case reports. Two agents in this class,
      celecoxib and rofecoxib, have been listed on the Pharmaceutical Benefits Scheme
      (PBS) for very broad indications in chronic arthropathies, suggesting that they
      will move into widespread community use. It is important to canvass the
      possibility that use of these agents could be associated with thrombotic events.

PMID- 11587284
TI  - Medical practice: still a higher calling.

PMID- 11587285
TI  - Hospitalised patients' views on doctors and white coats.
AB  - OBJECTIVES: To determine hospitalised patients' feelings, perceptions and
      attitudes towards doctors and how these are affected by whether or not doctors
      wear a white coat. DESIGN: Cross-sectional questionnaire survey. SETTING: The
      medical and surgical wards of two Sydney teaching hospitals, on one day in
      January 1999. PATIENTS: 154 of 200 consecutive patients (77%). MAIN OUTCOME
      MEASURES: The effects of white-coat-wearing on patients' feelings and ability to
      communicate and on their perceptions of the doctor; why patients think doctors
      wear white coats and their preferences for the wearing of white coats and
      doctors' attire in general; and patients' rating of the importance of these
      effects and preferences. RESULTS: Patients reported that white-coat-wearing
      improved all aspects of the patient-doctor interaction, and that when doctors
      wore white coats they seemed more hygienic, professional, authoritative and
      scientific. The more important that patients considered an aspect, the greater
      the positive effect associated with wearing a white coat. From a list of doctors'
      reasons for wearing white coats, patients thought that doctors wore white coats
      because it made them seem more professional, hygienic, authoritative, scientific,
      competent, knowledgeable and approachable. 36% of the patients preferred doctors
      to wear white coats, 19% preferred them not to wear white coats and 45% did not
      mind. CONCLUSIONS: Patients reported feeling more confident and better able to
      communicate with doctors who wore white coats. The recognition, symbolism and
      formality afforded by a white coat may enhance communication and facilitate the
      doctor-patient relationship.

PMID- 11587286
TI  - Complementary medicine and vitamin A toxicity in children.

PMID- 11587287
TI  - Doctors have become defrocked.

PMID- 11587288
TI  - Clothes do not maketh the man.

PMID- 11587289
TI  - Aesthetics or function?

PMID- 11587290
TI  - The stethoscope has replaced the white coat.

PMID- 11587291
TI  - Doctor? Nurse? Cleaner?

PMID- 11587292
TI  - Hospital staff need to be identifiable.

PMID- 11587293
TI  - Preventive medicine.

PMID- 11587294
TI  - Graduation ceremonies do not need white coats.

PMID- 11587295
TI  - Patient demographics may influence white coat preferences.

PMID- 11587296
TI  - Changes in the quality of diabetes care between 1994 and 1999.

PMID- 11587298
TI  - Herbal medicine.

PMID- 11587297
TI  - The effects of Chinese medicinal herbs on postmenopausal vasomotor symptoms of
      Australian women.

PMID- 11587299
TI  - Prejudice against mental illness.

PMID- 11587301
TI  - Reaffirming professionalism in medicine.

PMID- 11587302
TI  - Screening and diagnostic practices for chlamydia infections in New Zealand.
AB  - AIMS: To identify screening and diagnostic practices for chlamydia infection in
      New Zealand. METHODS: Postal survey of doctors and nurses at all sexual health,
      family planning, youth and student clinics, and randomly selected general
      practitioners (GPs). RESULTS: Most respondents recognised chlamydia infection as
      a cause of pelvic inflammatory disease and infertility in females, and
      epididymitis and non-gonococcal urethritis in males. Ectopic pregnancy and
      conjunctivitis were less commonly recognised by GPs and student and youth centre
      doctors. Sterile pyuria and arthritis were well recognised only by sexual health
      doctors. Female doctors were significantly more likely to recognise signs and
      symptoms than male doctors. GPs were less likely than other respondents to screen
      for chlamydia infection. Sexual health doctors and nurses were more likely to
      remove cervical secretions prior to taking endocervical specimens. Contact
      tracing was regarded as very important by only a quarter of family planning
      respondents, compared with over 80% of other respondents. CONCLUSIONS: While
      respondents recognised most signs, symptoms, and sequelae of chlamydia infection,
      some important features were not well recognised. Screening practices varied, and
      many endocervical specimens were taken incorrectly. Given the long-term health
      consequences and cost of chlamydia infection sequelae, screening guidelines are
      urgently required.

PMID- 11587303
TI  - A case of infectious tuberculosis on two long-haul aircraft flights: contact
      investigation.
AB  - AIM: During a five-week period in 1996, a passenger with highly infectious
      tuberculosis travelled on five long-haul aircraft flights. We investigated
      passengers and crew on two of these flights to identify whether transmission of
      Mycobacterium tuberculosis had occurred. METHODS: Crew and passengers were
      identified from airline and immigration records. Contacts were notified of their
      exposure and invited to attend their local public health clinic. At the clinic, a
      questionnaire was administered by a public health worker, and a Mantoux skin test
      was performed. When indicated, a second test was carried out twelve weeks later.
      Test positivity and conversion were defined according to the 1996 New Zealand
      tuberculosis control guidelines. RESULTS: Data were obtained on 206 (87%) of the
      238 contacts. Twenty four contacts had a positive Mantoux test result, four of
      which were conversions. All of these contacts had at least one other major risk
      factor for a positive result, such as a previous BCG vaccination (n=17) or having
      lived in a country in which tuberculosis is endemic (n=15). To our knowledge, no
      contacts have subsequently developed tuberculosis disease. CONCLUSIONS: The
      investigation produced inconclusive evidence about the hypothesis that
      Mycobacterium tuberculosis was transmitted on one or both of these flights.

PMID- 11587304
TI  - Marijuana use in New Zealand, 1990 and 1998.
AB  - AIMS: To examine changes in marijuana use in a metropolitan region and a
      provincial/rural region in New Zealand between 1990 and 1998. METHODS: Two random
      sample surveys of people aged 15 -45 years were carried out in Auckland and Bay
      of Plenty regions in 1990 and 1998, using a computer-assisted telephone
      interviewing system. RESULTS: Use of marijuana in the last twelve months
      increased in the metropolitan sample from 18% to 22%, but not in the provincial
      area. Those who had ever tried marijuana increased from 43% of the total sample
      in 1990 to 52% in 1998. Use was higher among men than women, but had increased
      among women. There was a trend towards more frequent users of marijuana (ten or
      more occasions in the previous 30 days), from 2.4% to 3.2%. CONCLUSIONS:
      Experience of marijuana was slightly more common in 1998 than in 1990, but
      increases in recent use were small and were found only in the metropolitan area.
      The increase in use was relatively limited: only one in five of each sample had
      used marijuana in the past year, and opportunity to use marijuana by non-users
      had not increased. Use was predominantly casual and social, and most who had
      tried marijuana no longer used the drug. However, the age at which first use
      occurred appeared to have declined.

PMID- 11587305
TI  - Women in rural general practice: the stresses and rewards.
AB  - AIMS: There is a shortage of general practitioners (GPs) in New Zealand rural
      areas, especially women GPs. An exploratory study was undertaken to ascertain why
      some women become rural GPs and to identify some of the significant stresses and
      rewards of rural practice for women. METHODS: Qualitative interviews were carried
      out with fourteen rural women GPs from around the North Island during 1999.
      RESULTS: Major issues identified from the interviews included on-call duty,
      locums, isolation, continuing medical education and the difficulty combining a
      family with the demands of rural practice. CONCLUSIONS: Based on the findings,
      recommendations are made to aid recruitment and retention of rural GPs,
      particularly women rural GPs.

PMID- 11587306
TI  - Bartonella henselae neuroretinitis in cat scratch disease.

PMID- 11587307
TI  - New Zealand doctors--a breed apart.

PMID- 11587308
TI  - The Cull report: requiring health providers to report complaints.

PMID- 11587309
TI  - Obtaining consent for epidural analgesia for women in labour--again.

PMID- 11587310
TI  - Tobacco and taking responsibility--again.

PMID- 11587311
TI  - Responsibilities of doctors in management and governance.

PMID- 11587312
TI  - Diabetes risks in Pacific Island communities.

PMID- 11587313
TI  - Prehospital thrombolysis.

PMID- 11587314
TI  - Unsubstantiated claims?

PMID- 11587315
TI  - Spinal cord stimulation for angina.

PMID- 11587316
TI  - Mandatory reporting of incompetence.

PMID- 11587317
TI  - Closing which gaps--why must rural people continue to pay for health services
      that urban areas get free?

PMID- 11587319
TI  - Rule 6 of the Health Information Privacy Code 1994.

PMID- 11587318
TI  - The health service implications of lung cancer incidence and the Maori population
      structure.

PMID- 11587320
TI  - A message of hope to those in painful expectation of death.

PMID- 11587321
TI  - Microanalysis using secondary electrons in scanning electron microscopy.
AB  - A recent study of secondary electron (SE) spectra in an Auger spectrometer
      demonstrated unique features indicative of the chemical nature of the tested
      material. The scanning electron microscope (SEM) naturally generates SEs;
      therefore, in this paper, we combine the concept of using differential voltage
      contrast (DVC) with SE spectroscopy to identify the chemical nature of a
      material. It is demonstrated that this method reveals the uniqueness of electron
      energy distribution in the conduction band of a solid or, what is the same, the
      uniqueness of a build-up of the outer electron shell system, and avoids errors
      due to the changes in the angular distribution or yield of the SE in the SEM. A
      theory of this new microanalytical method is developed. The experimental
      limitations of the SEM for this type of study are examined as well.

PMID- 11587322
TI  - Application of the low-loss scanning electron microscope image to integrated
      circuit technology. Part 1--Applications to accurate dimension measurements.
AB  - Scanning electron microscopes (SEMs) are the most extensively used tools for
      dimensional metrology and defect inspection for integrated circuit technologies
      with 180 nm and smaller features. Currently, almost all SEMs are designed to
      collect as many secondary and backscattered electrons as possible. These signals
      are mainly secondary electrons (SE1, SE2, and SE3) detected with various
      detection schemes. To facilitate the electron collection, very strong electric
      and magnetic fields are applied not just in the path of the primary electron beam
      but to the emerging electrons as well. These new systems provide strong signals,
      thus better signal-to-noise ratio, and thus resulting in higher throughput than
      older ones. On the other hand, the use of secondary electrons means that
      measurement results are much more prone to the detrimental effects of electron
      beam interactions, sample charging, and sample contamination than measurements
      with higher-energy backscattered electrons. The use of backscattered electrons,
      especially low-loss electrons (LLE), can provide better surface sensitivity, edge
      accuracy, and repeatability, possibly at the expense of measurement speed. This
      two-part study investigates the benefits and drawbacks of low-loss electron
      imaging to edge characterization for dimensional metrology and enhancement of
      fine surface features done through filtration or separation of the generated LLE
      signal and the use of energy-dependent signals. Part 1 reviews and illustrates
      the potential for accurate dimensional measurements at low accelerating voltage
      by LLE, and Part 2 will concentrate on the enhancement of surface features in
      chemical-mechanically planarized specimens with the use of a novel LLE detector.

PMID- 11587323
TI  - Light collection efficiency and light transport in backscattered electron
      scintillator detectors in scanning electron microscopy.
AB  - Experimentally, scintillator detectors used in scanning electron microscopy (SEM)
      to record backscattered electrons (BSE) show a noticeable difference in detection
      efficiency in different parts of their active zones due to light losses transport
      in the optical part of the detector. A model is proposed that calculates the
      local efficiency of the active parts of scintillator detectors of arbitrary
      shapes. The results of these calculations for various designs are presented.

PMID- 11587325
TI  - Experimental data and model simulations of beam spread in the environmental
      scanning electron microscope.
AB  - This work describes the comparison of experimental measurements of electron beam
      spread in the environmental scanning electron microscope with model predictions.
      Beam spreading is the result of primary electrons being scattered out of the
      focused beam by interaction with gas molecules in the low-vacuum specimen
      chamber. The scattered electrons form a skirt of electrons around the central
      probe. The intensity of the skirt depends on gas pressure in the chamber, beam
      gas path length, beam energy, and gas composition. A model has been independently
      developed that, under a given set of conditions, predicts the radial intensity
      distribution of the scattered electrons. Experimental measurements of the
      intensity of the beam skirt were made under controlled conditions for comparison
      with model predictions of beam skirting. The model predicts the trends observed
      in the experimentally determined scattering intensities; however, there does
      appear to be a systematic deviation from the experimental measurements.

PMID- 11587324
TI  - Quality measures in applications of image restoration.
AB  - We describe a new method for the estimation of image quality in image restoration
      applications. We demonstrate this technique on a simulated data set of
      fluorescent beads, in comparison with restoration by three different
      deconvolution methods. Both the number of iterations and a regularisation factor
      are varied to enforce changes in the resulting image quality. First, the data
      sets are directly compared by an accuracy measure. These values serve to validate
      the image quality descriptor, which is developed on the basis of optical
      information theory. This most general measure takes into account the spectral
      energies and the noise, weighted in a logarithmic fashion. It is demonstrated
      that this method is particularly helpful as a user-oriented method to control the
      output of iterative image restorations and to eliminate the guesswork in choosing
      a suitable number of iterations.

PMID- 11587326
TI  - Single-image signal-to-noise ratio estimation.
AB  - A method for estimating the signal-to-noise ratio from a single image is
      presented in this paper. The autocorrelation-based technique requires that image
      details be correlated over distances of a few pixels, while the noise is assumed
      to be uncorrelated from pixel to pixel. The latter is shown to be a good
      approximation in the case of scanning electron microscope (SEM) images provided
      that the video signal is not band limited. The noise component is derived from
      the difference between the image autocorrelation at zero offset and an estimate
      of the corresponding noise-free autocorrelation. Nonlinear effects introduced by
      intensity saturation and their implications on the image signal-to-noise ratio
      are also discussed.

PMID- 11587327
TI  - Investigation of human hair fibers using lateral force microscopy.
AB  - Atomic force microscopy (AFM) and lateral force microscopy (LFM) were used to
      investigate the morphologic and surface changes associated with various surface
      modifications to human hair. These included extraction with a series of solvents,
      bleaching, and treatment with a cationic copolymer. The study assessed the
      ability of these techniques to distinguish the changes in surface properties,
      including morphology and friction coefficient, as manifested in changes brought
      about by the indicated surface modifications. While topographic morphology can
      easily be investigated with contact AFM. LFM offers an additional tool for
      probing the surface distribution of oils and waxes. The removal of surface lipids
      from the fiber surface was accomplished using soxhlet extraction with t-butanol
      and n-hexane, while the free internal lipids (within the fiber structure) were
      removed by extraction with a mixture of chloroform and methanol (70:30, v/v). In
      addition, the surface of hair was modified with the cationic polymer, co(vinyl
      pyrrolidone-methacrylamidopropyl trimethylammonium chloride [PVP/MAPTAC]), and
      its distribution on the surface was monitored. Ambient AFM and LFM studies of
      surface modified and native fibers clearly indicate that when investigated as a
      function of tip loading force, the different modifications result in changes of
      the friction coefficient, which increase in this order: native, bleached, solvent
      extracted, and polymer-treated hair. Friction images show surface variations that
      are interpreted as areas of varying lipid film coverage. In addition, topographic
      images of the fibers show the presence of small pores, which become increasingly
      prevalent upon solvent extraction.

PMID- 11587328
TI  - Direct wet surface imaging of an anaerobic biofilm by environmental scanning
      electron microscopy: application to landfill clay liner barriers.
AB  - To contain domestic waste and its associated pollution within a landfill,
      engineered mineral (clay) barriers are used and are designed to have a
      permeability of 1 x 10(-9) m/s (Westlake 1995). The rate of permeability of
      various porous media has shown to be influenced by the clogging of flow paths
      (media pores) due to biofilm formation (Charckalis and Marshall 1990, Cunningham
      et al. 1991). The term biofilm is given to describe the colonies of surface
      adherent microorganisms (Donlan et al. 1994). In this study, permeability
      experiments were built and modified to act as microcosms to investigate the
      influence of biofilm formation on the permeability of clay barriers. Traditional
      scanning electron microscopy methods disrupt or destroy the biofilm and previous
      anaerobic studies have involved building closed cells (such as miniature
      continuous culture chambers) that utilise light microscopes (Robin Jones et al.
      1997). This paper examines the application of the environmental scanning electron
      microscope (ESEM) to the direct examination of the clay interface and biofilm
      formation in situ within the microcosm.

PMID- 11587329
TI  - Strategies for optimum use of superposition diffractogram in scanning electron
      microscopy.
AB  - Characteristics of the superposition diffractogram used for precisely estimating
      scanning electron microscopy (SEM) resolution are investigated. It is shown that
      the choice of pixel density to satisfy the sampling theorem, the direction of
      scanning, the choice of image shift direction, the properties of the specimen,
      the effect of external disturbances such as vibration and stray magnetic fields,
      and the effect of the window function required in the Fourier transform, are all
      factors which must be considered in order to make the superposition diffractogram
      a practical technique. An additional important improvement required to exploit
      fully the ability of the superposition diffractogram, which potentially is very
      high, is a special scanning mode which employs a digital scan generator, and
      digital image processing technology with autocorrelation functions.

PMID- 11587330
TI  - Assessment of the retention properties of poly(vinyl alcohol) stationary phase
      for lipid class profiling in liquid chromatography.
AB  - Potentialities of polymerized vinyl alcohol on silica gel were assessed for class
      separation of simple lipids, sphingolipids, glyceroglycolipids and phospholipids
      by high-performance liquid chromatography. A screening of pure solvents in binary
      gradient elution and a chemometric approach was used to define a rugged two
      segment linear gradient formed from four solvents for total lipid class
      separation. Triethylamine and formic acid were added in all mobile phase
      components for acidic phospholipid separation and evaporative light scattering
      response enhancement. Simple analytical procedures are described for the analysis
      of complex lipid materials.

PMID- 11587331
TI  - Enantiomeric purity determination of malic acid in apple juices by multi-beam
      circular dichroism detection.
AB  - A multi-beam circular dichroism (CD) detector which is easily constructed by
      inserting inexpensive optics into a conventional photo-diode array detector has
      an advantage of simultaneous detection of the absorbance and CD. The enantiomeric
      purity determination of malic acid in beverages was performed by this detection
      system. Malic acid when complexed with Cu(II) was found to have an absorbance
      maximum at around 750 nm. The L-malic acid-Cu(II) complex showed a positive
      Cotton effect in its absorbance band and its anisotropy factor (delta
      epsilon/epsilon) was relatively large at about 1/170. This complex was retained
      on a reversed-phase column with the addition of racemic 2-hydroxy-3-methylbutyric
      acid to the mobile phase as the ligand. A plot of the relative peak areas between
      the CD and the absorption (delta abs/abs) versus optical purity showed good
      linearity with a correlation coefficient of 0.999, and the precision expressed as
      the relative standard deviation of the errors from the regression line was +/
      2.7% (2sigma). The accuracy of the proposed method was assessed by capillary
      electrophoresis. Eight commercially available juice products were analyzed using
      this method. Five of them were thought to be adulterated with synthetic malic
      acid.

PMID- 11587332
TI  - High-performance liquid chromatographic separation of the enantiomers of
      organophosphorus pesticides on polysaccharide chiral stationary phases.
AB  - High-performance liquid chromatographic separation of the individual enantiomers
      of 12 organophosphorus pesticides (OPs) was obtained on polysaccharide
      enantioselective HPLC columns using alkane-alcohol mobile phase. The OP
      pesticides were crotoxyphos, dialifor, fonofos, fenamiphos, fensulfothion,
      isofenphos, malathion, methamidophos, profenofos, crufomate, prothiophos and
      trichloronate. The enantiomers of fenamiphos, fensulfothion, profenofos and
      crufomate were separated on CHIRALPAK AD; the enantiomers of fenamiphos were also
      separated on CHIRALPAK AS; the enantiomers of methamidophos, crufomate and
      trichloronate were separated on CHIRALCEL OD; the enantiomers of crotoxyphos,
      dialifor, fonofos, malathion, prothiophos and trichloronate were separated on
      CHIRALCEL OJ; and the enantiomers of isofenphos were separated on CHIRALCEL OG.
      Baseline or partial separation of the enantiomers of six of these OP pesticides
      was obtained on CHIRALCEL OJ. In continued method development, the separation of
      the enantiomers of the 12 OPs was investigated more extensively on CHIRALCEL OJ
      to determine whether the mobile phase composition, flow-rate and column
      temperature could be optimized to yield at least partial separation of the
      enantiomers. Chromatographic conditions were found that gave either baseline or
      near baseline separations of the enantiomers of the 12 OPs on the CHIRALCEL OJ
      column.

PMID- 11587333
TI  - Identification and determination of glucuronides and their aglycones in Erigeron
      breviscapus by liquid chromatography-tandem mass spectrometry.
AB  - A novel, speedy and reliable LC-MS-MS method for the search, identification and
      quantitation of O-glycosides and their aglycones from plant resources was
      established by analyzing the extract of Erigeron breviscapus. The extract was
      directly infused to a triple-quadrupole MS-MS and major glucuronides in the
      extract were screened out with high confidence by a neutral loss scan for the
      loss of a gluconic acid. The identity of these glucuronides and their aglycones
      was further confirmed with LC-MS-MS. In addition to scutellarin, apigenin 7-O
      glucuronide, quercetin-3-O-glucuronide and their aglycones that were previously
      reported by others, we also confirmed by LC-MS-MS that remarkable amount of
      baicalin, an isomer of apigenin 7-O-glucuronide, presented in the extract of this
      plant, which had not been reported before. A satisfying quantitation of three
      glucuronides was also made by LC-MS-MS.

PMID- 11587334
TI  - Separation and purification of isoflavones from a crude soybean extract by high
      speed counter-current chromatography.
AB  - A set of isoflavones with a broad range of polarity including daidzin, glycitin,
      genistin, acetyldaidzin, glycitein, acetylgenistin and daidzein was separated
      from a crude soybean extract by high-speed counter-current chromatography using a
      two-step operation. Three solvent systems were used: chloroform-methanol-water
      (4:3:2, v/v); chloroform-methanol-n-butanol-water (4:3:0.5:2, v/v); and methyl
      tert.-butyl ether-tetrahydrofuran-0.5% aqueous trifluoroacetic acid (2:2:0.15:4,
      v/v). The first solvent system was used for separating less polar isoflavones and
      the second for more polar isoflavones by eluting the lower organic phase.
      Genistin and glycitin, which were only partially resolved in the chloroform
      system, were separated by the third solvent system. Each isolated component
      showed 98-99% purity as determined by high-performance liquid chromatography
      analysis. Their structures were identified by LC-MS.

PMID- 11587335
TI  - Determination of phytosiderophores by anion-exchange chromatography with pulsed
      amperometric detection.
AB  - Phytosiderophores of the mugineic acid family are separated by anion-exchange
      HPLC using NaOH gradient elution. Separation of mugineic acid (MA), 2'
      deoxymugineic acid (DMA), 3-hydroxymugineic acid (HMA) and 3-epi-hydroxymugineic
      acid (epi-HMA) is obtained within 15 min. Detection of the underivatised
      phytosiderophores is performed using pulsed amperometric detection (PAD) at pH
      13. The sensitivity of the detection increases in the order DMA < MA < HMA < epi
      HMA and respective detection limits of 5 microM (DMA), 1 microM (MA) and < 0.5
      microM (HMA, epi-HMA) are achieved. PAD is discussed in comparison with the well
      established fluorimetric detection method after post-column derivatisation with
      ortho-phthaldialdehyde. The main advantage of PAD is the simplicity of the method
      (no derivatisation) and the high sensitivity for hydroxylated mugineic acids. The
      method is used for the determination of phytosiderophores in root washings of
      iron-deficient and non-deficient wheat and barley plants.

PMID- 11587336
TI  - Analysis of oxytetracycline, tetracycline, and chlortetracycline in water using
      solid-phase extraction and liquid chromatography-tandem mass spectrometry.
AB  - A method using liquid chromatography-tandem mass spectrometry has been developed
      for determination of trace levels of tetracycline antibiotics in ground water and
      confined animal feeding operation waste water. Oxytetracycline (OTC),
      tetracycline (TC), and chlortetracycline (CTC) were extracted from water samples
      using both polymeric and C18 extraction cartridges. The addition of a buffer
      containing potassium phosphate and citric acid improved tetracycline recoveries
      in lagoon water. Method detection limits determined in reagent water fortified
      with 1 microg l(-1) OTC, TC, and CTC were 0.21, 0.20, and 0.28 microg l(-1).
      Method detection limits in lagoon water samples fortified at 20 microg l(-1) for
      OTC, TC, and CTC were 3.6, 3.1, and 3.8 microg l(-1). Variability in recovery
      from laboratory fortified blanks ranged from 86 to 110% during routine analysis.

PMID- 11587337
TI  - Application of microcolumn liquid chromatography and capillary electrophoresis
      with flame photometric detection for the screening of degradation products of
      chemical warfare agents in water and soil.
AB  - Microcolumn liquid chromatography (microLC) and capillary electrophoresis (CE)
      coupled on-line with flame photometric detection (FPD) have been used for the
      screening of polar breakdown products of chemical warfare agents in water and
      soil samples, provided during Official Proficiency Tests organized by the
      Technical Secretariat of the Organization for the Prohibition of Chemical
      Weapons. CE-FPD is shown to be a powerful and rapid method for the determination
      of alkylphosphonic acids, which are the breakdown products of organophosphorus
      nerve agents. Gradient elution microLC-FPD is more sensitive and robust but less
      rapid in the determination of these compounds. In addition, microLC-FPD can be
      applied to screen for hydrolysis products of sulfur mustard and its analogues.
      Both methods can be applied without prior derivatization and are extremely
      selective. In order to unambiguously identify the relevant compounds,
      electrospray ionization (tandem) mass spectrometry, gas chromatography-mass
      spectrometry and nuclear magnetic resonance spectrometry were applied.

PMID- 11587338
TI  - Dependence of the efficiency of a multicapillary column on the liquid phase
      loading method.
AB  - One of the main approaches employed to reach fast chromatographic separation is
      based on using columns containing up to 1000 capillaries with the diameter size
      down to 10-100 microm. The efficiency of such columns depends on the dispersion
      of the capillary radius and on the way of the liquid-film loading. We present
      general equations describing these effects. Specifically, we show theoretically
      and experimentally that the separation efficiency can be improved by using the
      loading methods specially designed in order to take into account correlation
      between the film thickness and capillary radius.

PMID- 11587339
TI  - Determination of organo-zinc based fungicides in timber treatments employing gas
      chromatographic analysis with mass selective detection and/or inductively coupled
      plasma atomic emission spectroscopy.
AB  - A method for the determination of zinc octoate (zinc 2-ethylhexanoate) and
      acypetacs zinc in occupational hygiene samples and wood treatments formulations
      is described. The zinc carboxylates are liquid-liquid partitioned between toluene
      and 1 M HCl, with the liberated acids being extracted into the toluene and zinc
      (chloride) into the acid. The carboxylic acids are then methylated using
      trimethylsilyldiazomethane-methanol and the resultant methyl esters are
      selectively and sensitively analysed by gas chromatography with mass selective
      detection (GC-MS). Alternatively, the zinc content of the acid extract can be
      analysed by inductively coupled plasma atomic emission spectroscopy (ICP-AES). GC
      MS is the preferred method of analysis for zinc octoate, where a single analyte
      (methyl-2-ethylhexanoate) is produced for analysis. Because acypetacs zinc
      contains a complex mixture of carboxylates, quantitative GC-MS analysis of the
      methyl esters produced is impractical and ICP-AES is the preferred method for
      quantitation. In this case, GC-MS can be used to confirm the identity of the
      product used. The analysis of occupational hygiene samples (cotton pads, gloves
      and socks as well as Tenax tubes and GF/A filters) spiked with metal carboxylates
      is demonstrated. Recoveries around 70-90% and reproducibilities of 5-23% (n=6-8)
      were typically achieved for the determination of tin octoate (a surrogate for
      zinc octoate) at spiking levels ranging from 4 to 190 microg per sampling device.
      Recoveries around 102-106% and reproducibilities of 10-12% (n=5-6) were typically
      achieved for acypetacs zinc at spiking levels ranging from 100 mg per sampling
      device. Reaction yields for the octoate methylation reaction were in the region
      of 85-87%. The method was used to monitor for occupational exposure to zinc
      octoate and acypetacs zinc during the application of wood treatments to fences.

PMID- 11587340
TI  - Automated multiple development thin layer chromatography for calystegines and
      their biosynthetic precursors.
AB  - Automated multiple development thin layer chromatography (AMD-TLC) was used for
      separation of calystegines, a class of nortropane alkaloids, and of precursors of
      their biosynthesis. The calystegines differ in the number of hydroxyl groups at
      the nortropane ring system and in the substitution pattern. A combination of TLC
      methods allows the separation of the individual calystegines and separation of
      possible precursors of the biosynthesis. Solvent combination, development time,
      the number of development steps, the drying time between each run and the
      preconditioning parameters of the silica gel TLC plates were optimised. Limits of
      detection were evaluated for several detection reagents.

PMID- 11587341
TI  - Rapid chiral on-chip separation with simplified amperometric detection.
AB  - The enantiomers of adrenaline, noradrenaline, ephedrine and pseudoephedrine were
      separated by capillary electrophoresis on a micromachined device. Detection was
      carried out with a new two-electrode amperometric detector, eliminating the need
      for individual counter and reference electrodes. Separation of the isomers was
      achieved by employing carboxymethyl-beta-cyclodextrin as chiral selector in the
      buffer, partly with the additional inclusion of the crown ether 18-crown-6. Plate
      numbers of up to 20,000, chiral resolutions of 2.5 and detection limits of the
      order of 10(-7) M were achieved. All separations were completed in less then 3
      min.

PMID- 11587342
TI  - On-column ligand synthesis coupled to partial-filling affinity capillary
      electrophoresis to estimate binding constants of ligands to a receptor.
AB  - This paper describes a two-step procedure whereby on-column ligand synthesis and
      partial-filling affinity capillary electrophoresis (PFACE) are sequentially
      coupled to each other to determine the binding constants of 9-fluorenylmethoxy
      carbonyl (Fmoc)-amino acid-D-Ala-D-Ala species to vancomycin (Van) from
      Streptomyces orientalis. In this technique four separate plugs of sample are
      injected onto the capillary column and electrophoresed. The initial sample plug
      contains a D-Ala-D-Ala terminus peptide and two non-interacting standards. Plugs
      two and three contain solutions of Fmoc-amino acid-N-hydroxysuccinimide (NHS)
      ester and running buffer, respectively. The fourth sample plug contains an
      increasing concentration of Van partially-filled onto the capillary column. Upon
      electrophoresis the initial D-Ala-D-Ala peptide reacts with the Fmoc-amino acid
      NHS ester yielding the Fmoc-amino acid D-Ala-D-Ala peptide. Continued
      electrophoresis results in the overlap of the plugs of Van and Fmoc-amino acid-D
      Ala-D-Ala peptide and non-interacting markers. Analysis of the change in the
      relative migration time ratio of the Fmoc-amino acid-D-Ala-D-Ala peptide relative
      to the non-interacting standards, as a function of the concentration of Van,
      yields a value for the binding constant. These values agree well with those
      estimated using other binding and ACE techniques.

PMID- 11587343
TI  - Separation of DNA fragments and single strand conformation polymorphism analysis
      in bare capillaries using poly(acrylamide-dimethylacrylamide) as a separation
      medium.
AB  - A short chain poly(acrylamide-dimethylacrylamide) (PADMA) was synthesized in
      aqueous phase using isopropanol as a chain transfer agent, and was characterized
      according to the chemical composition and molecular mass. This polymer can form a
      stable dynamic coating on the inner surface of the capillary, thereby suppressing
      the electroosmotic flow and DNA-capillary wall interaction. The sieving medium
      has low viscosity and capillary filling with this medium and medium replacement
      were conveniently carried out by commercial capillary electrophoresis
      instruments. The effects of components and concentration of copolymers on the
      separation of DNA fragments were investigated. Highly efficient separation of DNA
      fragments, successful single strand conformation polymorphism (SSCP) analysis and
      good reproducibility of the migration time were obtained in bare capillaries
      using these copolymers as sieving media. Our preliminary results demonstrate that
      PADMA will become an alternative matrix for DNA separation by capillary
      electrophoresis.

PMID- 11587344
TI  - High-performance liquid chromatographic method to screen and quantitate seven
      selective serotonin reuptake inhibitors in human serum.
AB  - A high-performance liquid chromatographic screening method (HPLC) is described
      for the determination of seven selective serotonin reuptake inhibitors (SSRIs)
      (fluvoxamine, milnacipran, paroxetine, sertraline, fluoxetine, citalopram,
      venlafaxine) and for three pharmacologically active N-demethylated metabolites
      (desmethylcitalopram, didesmethylcitalopram and norfluoxetine). A tricyclic
      antidepressant, clomipramine, was used as an internal standard. The method
      consists of liquid extraction of serum after alcalinisation at pH 9.50, followed
      by chromatography on a Beckman C18 reversed-phase column. Compounds were detected
      at 200.4 nm. The standard curves were linear over a working range of 50-1,000
      ng/ml for fluvoxamine, 15-1,000 ng/ml for fluoxetine, 25-500 ng/ml for
      norfluoxetine, 50-500 ng/ml for sertraline, 20-500 ng/ml for paroxetine, 25-550
      ng/ml for citalopram, 25-750 ng/ml for desmethylcitalopram, 25-800 ng/ml for
      didesmethylcitalopram, 25-650 ng/ml for milnacipran, and 25-500 ng/ml for
      venlafaxine. The quantitation limits of the method were 15 ng/ml for fluoxetine,
      20 ng/ml for paroxetine, 25 ng/ml for venlafaxine, norfluoxetine and citalopram,
      and its metabolites, 40 ng/ml for sertraline and 50 ng/ml for fluvoxamine. No
      interferences were noted with this sensitive and specific method which can be
      used for therapeutic drug monitoring.

PMID- 11587345
TI  - Adenosine nucleotides in rat bone measured by ion-pair reversed-phase high
      performance liquid chromatography: effect of hemorrhagic shock, with and without
      retransfusion of blood.
AB  - The measurement of bone adenosine nucleotides (ATP. ADP. AMP) using a simple HPLC
      procedure is described for rat tibia; the response to hemorrhagic shock with and
      without blood retransfusion is also described. With respect to the measurement of
      nucleotides, a number of validation criteria are met. In the anesthetized intact
      rat (Normal) there was a declining gradient of the three nucleotides, expressed
      as nmol per g dry matter, from proximal over middle to distal diaphysis, with the
      mean ratio ATP/ADP (0.21, 0.20, 0.20) and the mean energy charge (0.34, 0.31,
      0.30) being low. Irrespective of the anatomic site, hemorrhagic shock of 30-min
      duration evoked a further decrease versus Normal of ATP, ATP/ADP and energy
      charge. Blood retransfusion after shock kept nucleotides and other variables in
      the proximal and distal, but not the middle, diaphysis within normal limits. It
      was concluded that: (i) bone nucleotides are reliably measurable by HPLC,
      allowing the described method to be recommended for wider use in bone research
      and related areas; (ii) in contrast to more parenchymatous tissues, low ATP,
      ATP/ADP and energy charge may be characteristic for long bones, pointing towards
      different energy metabolism; and (iii) bone is a "shock organ", reflecting blood
      hypoperfusion, O2 deficiency and decreased ATP in this situation.

PMID- 11587346
TI  - A simple method for the assay of colistin in human plasma, using pre-column
      derivatization with 9-fluorenylmethyl chloroformate in solid-phase extraction
      cartridges and reversed-phase high-performance liquid chromatography.
AB  - A simple, selective and sensitive high-performance liquid chromatographic (HPLC)
      method is described for the determination of colistin in human plasma.
      Derivatization with 9-fluorenylmethyl chloroformate was performed in the same
      solid-phase extraction C18 cartridge used for sample pre-treatment, followed by
      reversed-phase HPLC with fluorimetric detection. Quantification was achieved
      using the ratio of the summed peak areas of colistin A and B derivatives to that
      of the derivative of netilmicin (internal standard). Linear calibration curves
      were obtained within the concentrations of colistin sulfate from 0.10 to 4.0 mg/l
      in plasma. Accuracy was within 10% and reproducibility (RSD) was less than 10%.

PMID- 11587347
TI  - Quantification of epimeric budesonide and fluticasone propionate in human plasma
      by liquid chromatography-atmospheric pressure chemical ionization tandem mass
      spectrometry.
AB  - A highly sensitive and selective liquid chromatography-atmospheric pressure
      chemical ionization tandem mass spectrometry assay was developed and validated
      for simultaneous determination of epimeric budesonide (BUD) and fluticasone
      propionate (FP) in plasma. The drugs were isolated from human plasma using C18
      solid-phase extraction cartridges, and epimeric BUD was acetylated with a mixture
      of 12.5% acetic anhydride and 12.5% triethylamine in acetonitrile to form the 21
      acetyl derivatives following the solid-phase extraction. Deuterium-labelled BUD
      acetate with an isotopic purity >99% was synthesized and used as the internal
      standard. The assay was linear over the ranges 0.05-10.0 ng/ml for epimeric BUD,
      and 0.02-4.0 ng/ml for FP. The inter- and intra-day relative standard deviations
      were <14.3% in the assay concentration range.

PMID- 11587348
TI  - Validation of a high-performance liquid chromatographic assay for the
      quantification of adenovirus type 5 particles.
AB  - An anion-exchange-high-performance liquid chromatography (AE-HPLC) method for the
      quantification of adenovirus type 5 (Ad5) total particles was validated according
      to performance criteria of precision, specificity, linearity of calibration and
      range, limit of detection, limit of quantification, accuracy and recovery. The
      viral particles were detected by absorbance at 260 nm using photodiode array
      detector (PDA). Cesium chloride (CsCl) purified Ad5 and lysate samples were used
      for the validation of the method. Relative standard deviations (RSDs) for the
      inter-day, intra-day precision and reproducibility for both the lysate and the
      Ad5 standard were less than 10 and 2% for the peak area and retention time,
      respectively. The method was specific for Ad5 which was eluted at 8.0 min. The
      presence of DNA does not affect the recovery of Ad5 particles for accurate
      quantification. Based on the error in prediction to be less than 10%, the working
      range was established between 2 x 10(10) and 7 x 10(10) VP/ml with correlation
      coefficient of 0.99975, standard deviation of 6.14 x 10(9) VP/ml and a slope of
      3.04 x 10(5) VP/ml. The recovery of the method varied between 88 and 106% in all
      of the lysate samples investigated which is statistically similar to 100%
      recovery at 95% confidence interval.

PMID- 11587349
TI  - High-performance liquid chromatographic assay for the determination of 2'-deoxy
      3'-thiacytidine (lamivudine) in human plasma.
AB  - A method for the quantification of 2'-deoxy-3'-thiacytidine (lamivudine, 3-TC),
      which incorporated the use of 3-isobutyl-methylxanthine as internal standard
      (I.S.) was developed and validated in human plasma, using HPLC with UV absorbance
      detection. Using solid-phase extraction, 3-TC and I.S. were selectively extracted
      from human plasma. Subsequently, chromatographic separation was performed using a
      YMC phenyl column with ion-pair chromatography and detection at 270 nm. The
      method was validated over a concentration range of 10 to 5,000 ng/ml using 0.5 ml
      of human plasma. The extraction recovery for both 3-TC and I.S. was greater than
      95%. The determination of inter- and intra-day precision (RSD) was less than 10%
      at all concentration levels, while the inter- and intra-day accuracy (%
      difference) was less than 6%.

PMID- 11587350
TI  - Determination of celecoxib in human plasma and rat microdialysis samples by
      liquid chromatography tandem mass spectrometry.
AB  - Methods for the determination of celecoxib in human plasma and rat microdialysis
      samples using liquid chromatography tandem mass spectrometry are described.
      Celecoxib and an internal standard were extracted from plasma by solid-phase
      extraction with C18 cartridges. Thereafter compounds were separated on a short
      narrow bore RP C18 column (30 x 2 mm). Microdialysis samples did not require
      extraction and were injected directly using a narrow bore RP C18 column (70 x 2
      mm). The detection was by a PE Sciex API 3000 mass spectrometer equipped with a
      turbo ion spray interface. The compounds were detected in the negative ion mode
      using the mass transitions m/z 380-->316 and m/z 366-->302 for celecoxib and
      internal standard, respectively. The assay was validated for human plasma over a
      concentration range of 0.25-250 ng/ml using 0.2 ml of sample. The assay for
      microdialysis samples (50 microl) was validated over a concentration range of 0.5
      20 ng/ml. The method was utilised to determine pharmacokinetics of celecoxib in
      human plasma and in rat spinal cord perfusate.

PMID- 11587351
TI  - Quantification of metronidazole in small-volume biological samples using narrow
      bore high-performance liquid chromatography.
AB  - A rapid, selective and sensitive HPLC assay has been developed for the routine
      analysis of metronidazole in small volumes of rat plasma, gastric aspirate and
      gastric tissue. The extraction procedure involves liquid-liquid extraction and a
      protein precipitation step. A microbore Hypersil ODS 3 microm (150 x 2.1 mm I.D.)
      column was used with a mobile phase consisting of acetonitrile-aqueous 0.05 M
      potassium phosphate buffer (pH 7) containing 0.1% triethylamine (10:90). The
      column temperature was at 25 degrees C and the detection was by UV absorbance at
      317 nm. The limit of detection was 0.015 microg ml(-1) for gastric juice aspirate
      and plasma and 0.010 microg g(-1) for gastric tissue (equivalent to 0.75 ng on
      column). The method was linear up to a concentration of 200 microg ml(-1) for
      plasma and gastric juice aspirate and up to 40 microg g(-1) for tissue, with
      inter- and intra-day relative standard deviations less than 14%. The measured
      recovery was at least 78% in all sample matrices. The method proved robust and
      reliable when applied to the measurement of metronidazole in rat plasma, gastric
      juice aspirate and gastric tissue for pharmacokinetic studies in individual rats.

PMID- 11587352
TI  - Development of a high-performance liquid chromatographic method for the
      determination of 11-keto-beta-boswellic acid in human plasma.
AB  - A validated HPLC method for the determination of 11-keto-beta-boswellic acid
      (KBA) in human plasma was developed. The method involves the solid-phase
      extraction of KBA from plasma followed by a separation with reversed-phase HPLC.
      Calibration was based on external standardisation and ranged between 0.1 and 2.0
      microg KBA per ml plasma. Linearity was established over the entire calibration
      range and in each case the coefficient of correlation (r2) was above 0.99. The
      recovery of KBA from plasma was 85.7%. It was further demonstrated that the
      method can be applied successfully to monitor the level of KBA in plasma.

PMID- 11587353
TI  - Determination of nandrolone and metabolites in urine samples from sedentary
      persons and sportsmen.
AB  - Metabolites of nandrolone were determined in the urine of several sportsmen,
      sedentary and post-menopausal women by capillary gas chromatography-mass
      spectrometry quadrupole (GC-MS) and capillary gas chromatography mass-mass
      spectrometry ion trap (GC-MS-MS) methods. The method employed was GC-EI-MS with
      17alpha-methyltestosterone as internal standard with ethyl ether extraction prior
      to selected ion monitoring of the bis(trimethylsilyl) ethers at ion masses m/z
      405 and 420 for the nandrolone metabolites, and 418 and 403 for nandrolone
      derivative. Recovery for nandrolone, 19-norandrosterone (19-NA) and 19
      noretiocholanolone (19-NE) was 97.20, 94.17 and 95.54%, respectively. Detection
      limits for nandrolone, 19-NA and 19-NE were 0.03, 0.01 and 0.06 ng/ml.
      Metabolites of nandrolone (19-NA and 19-NE) were found in 12.5% (n = 40) of
      sportsmen and 40% (n = 10) of post-menopausal women.

PMID- 11587354
TI  - Quantitative determination of gene expression in human lymphocytes assessed by
      reverse transcription-polymerase chain reaction coupled to high-performance
      liquid chromatography.
AB  - Gene expression in human lymphocytes was assessed using reverse transcription and
      polymerase chain reaction amplification followed by ion-pair reversed-phase
      chromatography analysis. Competitive PCR was used to quantitate the desired cDNAs
      with a polivalent competitor adaptable to multiple novel mRNAs estimations with
      minor changes. Accuracy was 11.27+/- 11.87% (n = 7), as determined using
      standards. The coefficients of variation of the assessment of human OK12b were 7%
      (n = 6), 7.68 attmol/microg of total RNA, and 21% (n = 6), 0.93 attmol/microg of
      total RNA. Sample-to-sample variation in the reverse transcription and in the
      quantity and quality of RNA was attenuated by normalising results to beta-actin
      mRNA expression. The correlation between the OK12b/beta-actin ratio and
      competitive assessments of OK12b was 0.984, n = 6. The correlation between HPLC
      results and an independent method based on radionuclide uptake by the product,
      detected by electrophoretic separation, was 0.848, n = 10.

PMID- 11587355
TI  - New antibody purification procedure using a thermally responsive poly(N
      isopropylacrylamide)-dextran derivative conjugate.
AB  - Through their specificity and affinity, antibodies are useful tools in research
      and medicine. In this study, we investigated a new type of chromatographic method
      using a thermosensitive polymer for the purification of antibodies against a
      dextran derivative (DD), as a model. The thermally reversible soluble-insoluble
      poly(N-isopropylacrylamide)-dextran derivative conjugate, named poly(NIPAAm)-DD,
      has been synthesized by conjugating amino-terminated poly(N-isopropylacrylamide)
      to a DD via ethyl-3-(3-dimethylaminopropyl)-carbodiimide. On one hand, this
      report describes the two steps of poly(NIPAAm)-DD conjugation and
      characterization. On the other hand, the poly(NIPAAm)-DD conjugate was used as a
      tool to purify polyclonal antibodies in serum samples from rabbits subcutaneously
      immunized with the derivatized dextran. Antibodies were purified and quantified
      by immunoenzymatic assays. Our results indicate that antibodies recognized both
      DD and poly(NIPAAm)-DD. In contrast, they did not bind to native poly(NIPAAm) or
      poly(NIPAAm) conjugated with another anionic dextran. We conclude that the
      conjugation of a polysaccharide to poly(NIPAAm) leads to an original and
      efficient chromatographic method to purify antibodies. Moreover, this novel
      method of purification is rapid, sensitive, inexpensive and could be used to
      purify various types of antibodies.

PMID- 11587356
TI  - High-performance liquid chromatographic determination of diazepam in plasma of
      children with severe malaria.
AB  - A sensitive, selective and reproducible reversed-phase HPLC method with
      ultraviolet detection was developed for the quantification of diazepam in small
      plasma samples from children with severe malaria. The method involves plasma
      deproteinization with acetonitrile, followed by liquid-liquid extraction with
      ethyl acetate-n-hexane. Diazepam was eluted at ambient temperatures from a
      reversed-phase C18 column with an acidic (pH 3.5) aqueous mobile phase (10 mM
      KH2PO4-acetonitrile, 69:31, v/v). Calibration curves in spiked plasma were linear
      from 10 to 200 ng (r2 > or = 0.99). The limit of detection was 5.0 ng/ml, and
      relative recoveries at 25 and 180 ng were >87%. Intra- and inter-assay relative
      standard deviations were <15%. There was no interference from drugs commonly
      administered to children with severe malaria (phenobarbitone, phenytoin,
      chloroquine, quinine, sulfadoxine, pyrimethamine, halofantrine, cycloguanil,
      chlorcycloguanil, acetaminophen and salicylate). This method has been used for
      monitoring plasma diazepam concentrations in children with seizures associated
      with severe malaria.

PMID- 11587357
TI  - Validated methods for direct determination of hydroquinone glucuronide and
      sulfate in human urine after oral intake of bearberry leaf extract by capillary
      zone electrophoresis.
AB  - Bearberry leaf extracts are used in herbal medicinal products for the treatment
      of lower urinary tract infections. Two metabolites of the major phenolic
      constituent in the extract, arbutin (hydroquinone-1-O-beta-D-glucoside), must be
      assumed to be precursors of the active disinfectant principle hydroquinone. In
      order to assay the renal elimination of these two metabolites. i.e., hydroquinone
      conjugates with glucuronic and sulfuric acid, two separate capillary
      electrophoresis methods have been developed. Both methods were validated
      according to the criteria for validation of pharmaceutical bioanalytical methods
      as drafted by the US Department of Health and Human Services. 1998. As there is
      little sample preparation necessary, both methods are very suitable for urine
      analysis with large sample numbers as frequently coming up in the course of
      pharmaceutical bioavailability, bioequivalence and pharmacokinetic studies.

PMID- 11587358
TI  - New strategies for cancer therapy in the 21st century.
AB  - The development of new anticancer drugs, radiation therapy devices, and surgical
      techniques has improved the survival and quality of life of cancer patients.
      Despite these advances, many adverse events prevent patients from receiving
      treatment in comfort, and a majority of patients die from recurrent disease. The
      limitations of treatment in terms of effectiveness and tolerability have driven
      researchers to develop new strategies to reduce treatment-related toxicity and
      improve the survival rates of cancer patients.

PMID- 11587359
TI  - Phosphatidyl inositol signaling by BCR/ABL: opportunities for drug development.
AB  - The t(9;22) translocation associated with chronic myelogenous leukemia (CML)
      fuses the c-ABL gene on chromosome 9 with the BCR gene on chromosome 22,
      resulting in the production of one or more of a family of chimeric oncoproteins,
      p190, p210, or p230 BCR/ABL. These proteins have activated ABL kinase activity
      and are located in the cytoplasm of CML cells, predominantly in the cytoskeleton.
      Recent studies have led to the identification of numerous potential substrates
      for BCR/ABL, including many proteins that normally function in signal
      transduction pathways downstream from hematopoietic growth factor receptors.
      BCR/ABL is autophosphorylated on tyrosine residues and attracts a variety of
      adapter proteins and other signaling proteins, setting up large signaling
      complexes that ultimately result in growth. viability, and adhesion signals.
      Using new in vitro and animal model systems, it is now becoming possible to link
      specific signaling pathways to biological abnormalities in CML cells.
      Furthermore, the relative importance of some BCR/ABL-activated pathways is
      becoming clear. In vivo studies in certain lines of transgenic mice suggest that
      the antiapoptotic effect of Bcr/Abl is more important than previously thought.
      Our current studies indicate important roles for phosphoinositide 3-kinase/Akt
      and for STAT molecules. As a result of these more detailed biochemical analyses
      of BCR/ABL function, new targets for future drug development have been
      identified.

PMID- 11587360
TI  - Histone deacetylases and transcriptional therapy with their inhibitors.
AB  - Acute promyelocytic leukemia (APL) is characterized by the expansion of malignant
      myeloid cells blocked at the promyelocytic stage of hemopoietic development and
      is invariably associated with reciprocal chromosomal translocations involving the
      retinoic acid receptor alpha (RARalpha) gene on chromosome 17. RARalpha variably
      fuses to PML, PLZF, NPM, NuMA, and Stat5B genes (X genes/proteins). These
      translocations are balanced and reciprocal, thus leading to the generation of X
      RARalpha and RARalpha-X fusion genes of which the products coexist in the APL
      blast. The invariable involvement in these translocations of RARalpha, a
      prototypical transcription factor, makes APL a compelling example of aberrant
      transcriptional mechanisms in the etiopathogenesis of cancer. This paper focuses
      on the recent progress in defining the molecular mechanisms underlying APL
      pathogenesis and addresses how this new understanding has allowed the proposal
      and development of novel therapeutic strategies with compounds such as histone
      deacetylase inhibitors and inorganic arsenicals such as As2O3 which are currently
      being tested in murine leukemia models as well as in human APL patients. In
      particular, the crucial role played by the aberrant transcriptional activities of
      X-RARalpha and RARalpha-X fusion proteins in APL pathogenesis is discussed by
      reviewing the relevant therapeutic implications resulting from this analysis.

PMID- 11587361
TI  - Histone deacetylase as a new target for cancer chemotherapy.
AB  - Trichostatin A (TSA) and trapoxin (TPX), inhibitors of the eukaryotic cell cycle
      and inducers of morphological reversion of transformed cells, inhibit histone
      deacetylase (HDAC) at nanomolar concentrations. Recently, FK228 (also known as
      FR901228 and depsipeptide) and MS-275. antitumor agents structurally unrelated to
      TSA, have been shown to be potent HDAC inhibitors. These inhibitors activate the
      expression of p21Waf1 in a p53-independent manner. Changes in the expression of
      regulators of the cell cycle, differentiation, and apoptosis with increased
      histone acetylation may be responsible for the cell cycle arrest and antitumor
      activity of HDAC inhibitors. TSA has been suggested to block the catalytic
      reaction by chelating a zinc ion in the active site pocket through its hydroxamic
      acid group. On the other hand, an epoxyketone has been suggested to be the
      functional group of TPX capable of alkylating the enzyme. We synthesized a novel
      TPX analogue containing a hydroxamic acid instead of the epoxyketone. The hybrid
      compound, called cyclic hydroxamic-acid-containing peptide 1 (CHAP1) inhibited
      HDAC at low nanomolar concentrations. The HDAC1 inhibition by CHAPI was
      reversible, as is that by TSA, in contrast to irreversible inhibition by TPX.
      Interestingly, HDAC6, but not HDAC1 or HDAC4, was resistant to TPX and CHAP1,
      while TSA inhibited these HDACs to a similar degree. CHAP31, the strongest HDAC
      inhibitor obtained from a variety of CHAP derivatives, exhibited antitumor
      activity in BDF1 mice bearing B16/BL6 tumor cells. These results suggest that
      CHAP31 is promising as a novel therapeutic agent for cancer treatment, and that
      CHAP may serve as a basis for new HDAC inhibitors and be useful for combinatorial
      synthesis and high-throughput screening.

PMID- 11587362
TI  - FLT3 tyrosine kinase as a target molecule for selective antileukemia therapy.
AB  - Fusion gene products such as PML-RARalpha and BCR-ABL generated by leukemia
      specific chromosomal translocations have been identified as target molecules for
      the treatment of leukemia. Here we describe one possibility for extending the
      frontier of mechanism-based medicine for acute myeloid leukemia (AML). FLT3, a
      receptor tyrosine kinase (RTK) preferentially expressed in hematopoietic
      progenitor cells, frequently has a gain-of-function mutation in AML. To search
      for FLT3-targeted compounds, we screened the growth-inhibitory effects of several
      tyrosine kinase inhibitors (TKIs) on mutant FLT3-transformed 32D cells.
      Herbimycin A at a concentration of 0.1 microM markedly inhibited the growth of
      the transfectants but at that concentration was ineffective in parental 32D
      cells. It suppressed the constitutive tyrosine phosphorylation of the mutant
      FLT3, but not the phosphorylation of the ligand-stimulated wild-type FLT3. In
      mice transplanted with transformed 32D cells, the administration of herbimycin A
      completely prevented leukemia progression. Recent studies have indicated that
      herbimycin A binds directly with HSP90, a molecular chaperone, and destabilizes
      HSP90-associated proteins. Another HSP90 inhibitor, radicicol, also induced
      apoptosis selectively in transformed 32D cells. HSP90 is a promising target for
      the treatment of AML with mutant FLT3.

PMID- 11587363
TI  - Mechanisms of transcriptional repression by the t(8;21)-, t(12;21)-, and inv(16)
      encoded fusion proteins.
AB  - AML-1 is one of the most frequently translocated genes in human leukemia. AML-1
      binds DNA and activates or represses transcription, while the chromosomal
      translocation fusion proteins in acute myeloid leukemia subvert these functions.
      The t(8;21) is the second most frequent translocation in acute myeloid leukemia
      and creates a fusion between the DNA binding domain of AML-1 and the ETO (also
      known as MTG8) corepressor. The t(12;21) is found in up to 25% of pediatric B
      cell acute lymphoblastic leukemias and fuses the ETS family transcription factor
      TEL to the amino terminus of AML-1. In addition, the inv(16), the most frequent
      translocation in acute myeloid leukemia, fuses the AML-1 cofactor CBFbeta to the
      smooth muscle myosin heavy chain MYH11. Both the t(8;21) and t(12;21) create
      transcriptional repressors that impair AML-1 target gene expression. We
      demonstrated that the fusion proteins encoded by these translocations contact the
      nuclear hormone corepressors (N-CoR/SMRT), mSin3A, and histone deacetylases. We
      have also found that both TEL and AML-1 interact with mSin3A. TEL also binds N
      CoR and histone deacetylase-3, indicating that wild-type TEL is a transcriptional
      repressor. The t(12;21) fuses the mSin3A interaction domain of TEL to AML-1 to
      transform AML-1 from a regulated to an unregulated transcriptional repressor. The
      recognition that AML-1 interacts with mSin3A to repress transcription suggested
      that the inv(16) fusion protein might also repress the transcription of AML-1
      target genes. In fact, the inv(16) encodes a protein that cooperates with AML-1
      to repress transcription. The inv(16) fusion protein was found in a ternary
      complex with AML-1 and mSin3A, suggesting that the inv(16) also acts by
      recruiting transcriptional corepressors and histone deacetylases.

PMID- 11587364
TI  - Oncogenic mechanisms of Evi-1 protein.
AB  - Although Evi-1 is thought to promote growth or block differentiation in some cell
      types, its biological functions have not been elucidated. To explore the
      mechanisms underlying Evi-1-induced oncogenesis, we investigated whether Evi-1
      affects the signaling of transforming growth factor beta (TGF-beta), which
      inhibits proliferation of a wide range of cell types and is one of the most
      studied growth regulatory factors. We demonstrated that Evi-1 represses TGF-beta
      signaling and antagonizes its growth-inhibitory effects. Two separate regions of
      Evi-1 are responsible for this repression, one of which is the first zinc-finger
      domain. Through this domain, Evi-1 physically interacts with Smad3, an
      intracellular mediator of TGF-beta signaling, thereby suppressing the
      transcriptional activity of Smad3. These results define a novel function of Evi-1
      as a repressor of signaling components of TGF-beta. We also demonstrated that Evi
      1 represses Smad-induced transcriptional activation by recruiting CtBP as a
      corepressor. Evi-1 associates with CtBP1 through one of the CtBP-binding
      consensus motifs within the region from amino acid 544 to 607, and this
      association is required for the efficient inhibition of TGF-beta signaling. A
      specific histone deacetylase (HDAc) inhibitor, trichostatin A (TSA), alleviates
      Evi-1-mediated repression of TGF-beta signaling, suggesting that HDAc is involved
      in transcriptional repression by Evi-1. This identifies a novel function of Evi-1
      as a member of corepressor complexes and suggests that aberrant recruitment of
      corepressors is one of the mechanisms involved in Evi-1-induced leukemogenesis.
      These results indicate that specific HDAc inhibitors may be useful in the
      treatment of Evi-1-induced neoplastic tumors, including myeloid leukemias.

PMID- 11587365
TI  - Can we conquer cancer in the twenty-first century?
AB  - The twentieth century recorded the greatest advance in the control of human
      disease. From the beginning of recorded time, the human life-span changed little
      until the twentieth century. In the USA, it increased from 47.3 years in 1900 to
      76.4 years in 2000. The answer to the question of "Can we cure cancer in the
      twenty-first century?" requires an appreciation of the contemporary nature of our
      knowledge. At the beginning of the twentieth century, major problems were
      nutrition and infection. By 1950, the major causes of mortality and morbidity
      were still infectious diseases, such as syphilis, tuberculosis, poliomyelitis,
      and influenza. The 1950s and 1960s were the golden age of control of infectious
      diseases, while cancer, because of the aging of the population and the strong
      association between cancer and age, has become the major healthcare problem of
      the twenty-first century. Until 1960, no one had proposed or demonstrated that a
      systemic or metastatic form of cancer could be cured. In only 35-40 years not
      only have techniques for the early detection, prevention, and surgical and
      radiation therapy treatments improved, but at least 15-20% of patients with
      systemic/metastatic cancers can be cured with our current primitive systemic
      treatments. Prior to 1943, there was no chemotherapy. Prior to 1948, no one had
      described complete regression of a systemic cancer. There were no multi
      institution, randomized clinical trials prior to 1949. Additionally, combination
      chemotherapy, new drugs, bone marrow transplantation, broad-spectrum antibiotics
      to control infections, and platelets to control hemorrhage have been added in the
      past 50 years. The pace of progress extrapolates to a prediction of cancer
      control in the twenty-first century. The human genome has been sequenced, and it
      will be possible to identify expression profiles not only for malignant cells but
      for their normal counterparts. It is certain that interventions specific for
      control of the malignant transformation will be identified. An example of gene
      directed therapy is in acute promyelocytic leukemia where trans-retinoic acid is
      effective and contributes to cure. The signal transduction inhibitors, small
      molecules bioavailable orally and specific for interfering with signals resulting
      from ligand-receptor interactions, are a dramatic advance. Because cancer is a
      genetic disorder, the expanding field of genomics will certainly accelerate our
      progress toward the control of cancer. Finally, the twenty-first century will be
      an era of enhanced communication. The computer has given us the internet. Our
      communication in cyberspace is not only universal but instantaneous. Increases in
      the speed at which knowledge can be exchanged and the enormous capacity for
      storing new knowledge in cyberspace ensure that the pace of progress that we saw
      in the twentieth century will accelerate in the twenty-first. To address the
      question in the title of this paper, I believe that it is not a question of
      whether, but only of when.

PMID- 11587366
TI  - Remission induction therapy: the more intensive the better?
AB  - Intensive induction therapy in acute myeloid leukemia (AML) as in some other
      systemic malignancies is a strategy fundamentally different from post-remission
      strategies. Approaches such as consolidation treatment, prolonged maintenance,
      and autologous or allogeneic transplantation in first remission are directed
      against the minimal residual disease in which a malignant cell population has
      survived induction treatment and shows resistance due to special genetic or
      kinetic features. In contrast, induction therapy deals with naive tumor cells
      possibly different from their counterparts in remission in terms of their kinetic
      status and sensitivity. Therefore, in AML the introduction of intensification
      strategies into the induction phase of treatment has been suggested as a new step
      in addition to intensification in the postremission phase. As expected from the
      dose effects observed in post-remission treatment with high-dose cytarabine
      (AraC) or longer treatment, similar dose effects have been found in induction
      treatment both from the incorporation of high-dose AraC and from the double
      induction strategy used in patients up to 60 years of age. As a particular
      effect, patients with poor-risk AML according to an unfavorable karyotype, high
      LDH in serum, or a delayed response show longer survival following double
      induction containing high-dose AraC as compared to standard-dose AraC. A
      corresponding dose effect in the induction treatment of patients aged 60 years
      and older has been found with daunorubicin 60 vs 30 mg/m2 as part of the
      thioguanine/ AraC/daunorubicin (TAD) regimen with the higher dosage significantly
      increasing the response rate and survival in these older patients who represent a
      poor-risk group as a whole. Thus we have been able to demonstrate both in younger
      and older patients that a poor prognosis can be improved by a more intensive
      induction therapy. High-dose AraC in induction, however, exhibits cumulative
      toxicity in that repeated courses containing high-dose AraC in the post-remission
      period lead to long-lasting aplasias of about 6 weeks. Thus after intensive
      induction treatment, high-dose chemotherapy in remission may be practicable using
      stem-cell rescue and may contribute to a further improvement in the outcome in
      poor-risk as well as average-risk patients with AML. These approaches are
      currently under investigation by the German AML Cooperative Group (AMLCG). "The
      more intensive the better" is certainly not the way to go in the management of
      AML and other systemic malignancies but some increase in intensity may be
      possible and better.

PMID- 11587368
TI  - Evaluating the contribution of allogeneic and autologous transplantation to the
      management of acute myeloid leukemia in adults.
AB  - It has been widely accepted that patients in first remission of acute myeloid
      leukemia (AML) with a donor should receive an allograft, and many also believe
      that autologous transplantation is the next best option. Several factors cast
      doubt on these assumptions. For example, it is understood that patients who
      receive transplants are already selected to be at lower risk of relapse, and in
      addition the risk of relapse varies considerably among patients. This can be
      predicted by several risk factors, the most powerful of which is cytogenetics.
      Major collaborative group trials have attempted to evaluate the contribution of
      autograft and allograft to AML treatment in CR1. The EORTC-GIEMEMA, GOELAM, UK
      MRC, and US Intergroup trials randomized approximately 1200 patients to autograft
      versus, or in addition to, chemotherapy. Although relapse risk was reduced in all
      studies, overall survival was not better in three of the trials. Only the MRC
      trial showed a survival benefit, but only in patients beyond 2 years of follow
      up. Patients in these trials for whom donors were available were allocated to
      allogeneic transplant. This enabled the evaluation of allograft in a donor versus
      no donor (intent-to-treat) analysis. No study showed a survival benefit for the
      donor arm, although there was a substantial reduction in relapse risk. Analysis
      within risk groups suggests that transplantation for good-risk patients is not
      appropriate and the role of transplantation is uncertain in other groups.

PMID- 11587367
TI  - Acute myeloid leukemia in adults: where do we go from here?
AB  - Although 30-40% of newly diagnosed younger patients with acute myeloid leukemia
      (AML) can be cured with current approaches, the overall outcome has not improved
      in recent years. In addition, the outcome in adults > 60 years of age remains
      dismal with < 10% of patients achieving remission remaining alive and disease
      free. Results of randomized clinical trials in AML evaluating high-dose cytosine
      arabinoside, changes in anthracyclines, the use of hematopoietic growth factors,
      stem cell transplantation in first remission, and modulation of the multidrug
      resistance phenotype are reviewed. New directions for clinical trials include the
      use of nonmyeloablative allogeneic stem cell transplantation as a form of
      "immunotherapy", refinements in autologous stem cell transplantation, and
      possibly manipulations of neoangiogenesis in the bone marrow and incorporation of
      newer agents, such as gemtuzumab zogamicin into treatment regimens. It is likely,
      however, that future advances will be a consequence of a better understanding of
      the biology of leukemic stem cells, and issues related to such studies are
      discussed.

PMID- 11587369
TI  - Multicenter prospective study of interferon-alpha versus bone marrow
      transplantation for newly diagnosed patients with chronic myelogenous leukemia: a
      preliminary analysis.
AB  - Interferon-alpha (IFN-alpha) therapy was compared with bone marrow
      transplantation (BMT) in patients with chronic myelogenous leukemia (CML) in a
      multicenter, prospective study. Of 254 evaluable patients, 175 received IFN-alpha
      and 79 received allogeneic BMT, 50 of whom received transplants from human
      leukocyte antigen (HLA)-identical related donors and 29 from HLA-matched
      unrelated donors. Complete hematologic response was achieved by 148 patients
      (89%) in the IFN-alpha group and 53 (78%) in the BMT group. In the IFN-alpha
      group, a complete cytogenetic response was induced in 25 patients (15%), a
      partial cytogenetic response in 37 (23%), and a minor cytogenetic response in 41
      (25%). At a median follow-up of 38 months, in the IFN-alpha group the predicted 5
      year survival rate was 79%, and the predicted 5-year rate of remaining in chronic
      phase was 66%. In the BMT group the predicted 5-year survival rate was 72% for
      related-donor BMT and 67% for unrelated-donor BMT. Among low Sokal-risk patients,
      5-year survival did not differ between IFN-alpha therapy and BMT, irrespective of
      age. In higher Sokal-risk patients, survival for related-donor BMT and unrelated
      donor BMT tended to be better than that with IFN-alpha therapy in younger
      patients. On the other hand, in older patients, survival in the BMT group,
      especially for those receiving unrelated-donor BMT, appeared to be inferior to
      that in the IFN-alpha group. Unrelated-donor BMT can be recommended for high-risk
      younger patients. However, for older patients, it should be performed after
      careful consideration of prognostic factors such as age, Sokal score, and
      response to IFN-alpha.

PMID- 11587370
TI  - Analysis of prognostic factors in newly diagnosed patients with acute
      promyelocytic leukemia: the APL92 study of the Japan Adult Leukemia Study Group
      (JALSG).
AB  - All-trans-retinoic acid (ATRA) has been incorporated in front-line therapy for
      newly diagnosed acute promyelocytic leukemia (APL). We conducted a multicenter
      study of differentiation therapy with ATRA alone or in combination with
      chemotherapy followed by intensive postremission chemotherapy in patients with
      APL (the JALSG APL92 study), and analyzed prognostic factors to increase the cure
      rate in our subsequent trial. From 1992 to 1997, adult patients with newly
      diagnosed APL received oral ATRA 45 mg/m2 daily alone until complete remission
      (CR) if initial leukocyte counts were < 3.0x10(9)/l, and ATRA daily plus
      daunorubicin (DNR) 40 mg/m2x3 days plus enocitabine (BHAC) 200 mg/m2x5 days if
      leukocyte counts were > or =3.0 x 10(9)/l. If peripheral blasts exceeded
      1.0x10(9)/l during therapy, DNRx3 days plus BHACx5 days was added. After CR was
      achieved, three courses of consolidation and six courses of
      maintenance/intensification chemotherapy were administered. Of 376 patients
      enrolled, 369 were evaluable (median age 46 years, range 15-86 years; median
      leukocyte counts 2.0x10(9)/l), and 333 (90%) achieved CR (94% of patients treated
      with ATRA alone, 88% with ATRA plus later chemotherapy, 89% with ATRA plus
      initial chemotherapy, and 86% with ATRA plus initial and later chemotherapy). At
      a median follow-up of 45 months, the predicted 6-year overall and event-free
      survival (EFS) rates for all patients were 65% and 52%, respectively. Favorable
      prognostic factors for CR were younger age, no or mild purpura, high serum total
      protein level, low lactate dehydrogenase level, and no or mild disseminated
      intravascular coagulation (DIC). Favorable prognostic factors for EFS were
      leukocyte counts < 10.0x10(9)/l, mild DIC, and no sepsis during induction
      therapy. In the JALSG APL97 study, we intensified chemotherapy for patients with
      leukocyte counts > or =3.0x10(9)/l, and are randomly testing whether further
      chemotherapy is required for APL patients with negative PCR for PML/retinoic acid
      receptor alpha in the maintenance phase.

PMID- 11587371
TI  - Arsenic compounds as anticancer agents.
AB  - In this paper the use of arsenic compounds as anticancer agents in clinical
      trials and in in vitro investigations is reviewed, including the experience at
      our institute. Treatment of newly diagnosed and relapsed patients with acute
      promyelocytic leukemia (APL) with arsenic trioxide (As2O3) has been found to
      result in complete remission (CR) rates of 85-93% when given by intravenous
      infusion for 2-3 h at a dose of 10 mg/day diluted in 5% glucose saline solution.
      Patients exhibit a response in 28-42 days. CR rates after administration of
      Composite Indigo Naturalis tablets containing arsenic sulfide and of pure
      tetraarsenic tetrasulfide reached 98% and 84.9%, respectively. At higher
      concentrations (1-2 microM), arsenic induced apoptosis, while at lower
      concentrations (0.1-0.5 microM), it triggered cell differentiation in vitro.
      As2O3-induced apoptosis has been observed in many cancer cell lines, including
      esophageal carcinoma, gastric cancer, neuroblastoma, lymphoid malignancies, and
      multiple myeloma. Its effectiveness was confirmed in the treatment of multiple
      myeloma. Arsenic compounds are effective agents in the treatment of APL and their
      activity against other types of cancer requires further investigation.

PMID- 11587372
TI  - ST1571, a tyrosine kinase inhibitor for the treatment of chronic myelogenous
      leukemia: validating the promise of molecularly targeted therapy.
AB  - The deregulated tyrosine kinase activity of the Bcr-Abl fusion protein has been
      established as the causative molecular event in chronic myelogenous leukemia
      (CML). Thus the Bcr-Abl tyrosine kinase is an ideal target for pharmacologic
      inhibition. ST1571 (formerly CGP57148B), is an Abl-specific tyrosine kinase
      inhibitor that in preclinical studies selectively kills Bcr-Abl-containing cells
      in vitro and in vivo. The results of clinical studies have demonstrated the
      potential of molecularly targeted therapies, and ST1571 is emerging as a new
      therapeutic agent for CML.

PMID- 11587373
TI  - Nonmyeloablative stem cell transplantation for the treatment of cancer and life
      threatening nonmalignant disorders: past accomplishments and future goals.
AB  - Allogeneic bone marrow transplantation (BMT) or blood stem cell transplantation
      represents an important therapeutic tool for the treatment of otherwise incurable
      malignant and nonmalignant diseases. Until recently. autologous and allogeneic
      BMT or mobilized blood stem cell transplantation was used primarily to replace a
      malignant, genetically abnormal, or deficient immunohematopoietic compartment,
      and therefore highly toxic myeloablative regimens were considered mandatory for
      eradication of all undesirable host-derived hematopoietic elements. Our
      preclinical and ongoing clinical studies have indicated that more effective
      eradication of host immunohematopoietic system cells could be achieved by
      adoptive allogeneic cell therapy with donor lymphocyte infusion following BMT.
      Thus eradication of blood cancer cells, especially in patients with chronic
      myelogenous leukemia and less frequently in patients with other hematologic
      malignancies, can frequently be achieved despite complete resistance of such
      tumor cells to the maximum tolerated doses of chemoradiotherapy. Our cumulative
      experience suggests that graft vs leukemia (GVL) effects might be a useful tool
      for eradication of otherwise resistant tumor cells of host origin. Based on the
      cumulative clinical experience and experimental data in animal models of human
      diseases, it appears that induction of host vs graft tolerance as the first step
      may allow durable engraftment of immunocompetent donor lymphocytes, which may be
      used for induction of effective biologic warfare against host-type
      immunohematopoietic cells that need to be replaced, whether they are malignant,
      genetically abnormal, or self-reactive. Based on this rationale, we speculate
      that the therapeutic benefit of BMT may be increased by using safer conditioning
      as part of the transplantation procedure, with the goal of inducing host vs graft
      tolerance to enable subsequent induction of GVL, possibly graft vs tumor, or even
      graft vs autoimmunity effects, rather than attempting to eliminate host cells
      with hazardous myeloablative chemoradiotherapy. Our hypothesis suggests that
      effective BMT procedures might be accomplished without lethal conditioning of the
      host, using new, well-tolerated nonmyeloablative regimens, possibly minimizing
      immediate and late side effects related to myeloablative procedures. Recent
      clinical data suggest that effective BMT procedures may be accomplished with
      nonmyeloablative stem cell transplantation (NST) regimens, with no major
      toxicity. Thus new NST approaches may make BMT procedures safer for a spectrum of
      clinical indications in children and elderly individuals without lower or upper
      age limits, while minimizing procedure-related toxicity and mortality. Our
      cumulative data suggest that high-dose chemotherapy and radiation therapy may be
      successively replaced by more effective alloreactive donor lymphocytes, thus
      setting the stage for innovative therapeutic procedures with safer and more
      effective treatment of patients requiring BMT.

PMID- 11587374
TI  - Clinical trials of a mouse-human chimeric anti-CD20 monoclonal antibody
      (rituximab) for B cell non-Hodgkin's lymphoma in Japan.
AB  - Rituximab, a mouse-human chimeric anti-CD20 monoclonal antibody, induces
      apoptosis in B cell non-Hodgkin's lymphoma (B-NHL) cells, in addition to lysis by
      complement-dependent cytotoxicity and antibody-dependent cell-mediated
      cytotoxicity. A group of 12 patients with relapsed CD20+ B-NHL were enrolled in a
      phase I study; 4 received rituximab 250 mg/m2 and 8 375 mg/m2 once weekly for 4
      weeks. Grade 1 or 2 infusion-related toxicity such as 'flu-like symptoms and skin
      reactions were observed. Of the 11 patients eligible for study enrollment, 2
      achieved a complete response (CR) and 5 a partial response (PR). The T 1/2 of
      rituximab was 445+/-361 h, and serum rituximab levels were measurable at 3
      months. Thereafter, 90 relapsed patients with indolent B-NHL or mantle cell
      lymphoma (MCL) were enrolled in a phase II study and received rituximab 375
      mg/m2x4 weekly infusions. A central pathology review and an extramural review
      disclosed that 13 patients were ineligible for final analysis. Factors affecting
      response and progression-free survival (PFS) were analyzed in the remaining 77
      patients. The overall response rate (ORR) in indolent B-NHL and MCL was 61% (37/
      61, 95% CI 47-73%) and 46% (6/13, 95% CI 19-75%), respectively. The median PFS
      time was 245 days in indolent B-NHL and 111 days in MCL patients. Multivariate
      analysis revealed that the ORR was affected by the number of prior regimens
      (P=0.018) and that the PFS was affected by the following three factors: disease
      type (P = 0.000), presence of extranodal lesions (P=0.001). and number of prior
      regimens (P=0.007). The PFS times of patients with higher serum rituximab
      concentrations at day 14 (> or =70 microg/ml) and at 3 months (> or =10
      microg/ml) were significantly longer than those of patients with lower
      concentrations (P=0.006 and P=0.0001, respectively). In conclusion, rituximab is
      more effective in indolent B-NHL than in MCL. Several prognostic factors and
      serum rituximab concentrations are useful for predicting the therapeutic
      efficacy.

PMID- 11587375
TI  - Radioimmunotherapy for patients with relapsed B-cell non-Hodgkin lymphoma.
AB  - Clinical trials of an yttrium-90 (90Y)-conjugated monoclonal antibody to CD20 in
      patients with relapsed B cell non-Hodgkin lymphoma (NHL) are reviewed.
      Ibritumomab is the murine parent anti-CD20 antibody engineered to make the human
      chimeric antibody rituximab. Tiuxetan is an MX-DTPA linker chelator attached to
      ibritumomab to form ibritumomab tiuxetan (Zevalin). Ibritumomab tiuxetan can
      react with indium-111 (111In) or 90Y to form 111In-ibritumomab tiuxetan, which is
      used for dosimetry, or 90Y-ibritumomab tiuxetan, which is used for therapy of B
      cell NHL. In this report, the results of five separate clinical trials of
      ibritumomab tiuxetan are reviewed. Two phase I trials of 90Y-ibritumomab tiuxetan
      were performed, one using cold ibritumomab prior to 90Y-ibritumomab tiuxetan, and
      one using rituximab prior to 90Y-ibritumomab tiuxetan. The optimal schedule was
      found to be rituximab on days I and 8, and 90Y-ibritumomab tiuxetan 0.4 mCi/kg
      i.v. on day 8; no stem cells or prophylactic growth factors were used. A dose of
      0.3 mCi/kg was recommended for patients with a baseline platelet count of 100,000
      149,000x10(6)/l. The only significant toxicity was reversible myelosuppression.
      With this schedule, the overall response rate (ORR) was 67% of all patients and
      82% of those with low-grade NHL. The phase I/II trials were followed by a phase
      III trial that randomized 143 eligible patients to either rituximab or 90Y
      ibritumomab tiuxetan radioimmunoconjugate to demonstrate that the combination of
      the 90Y radioisotope to the murine anti-CD20 antibody provided additional
      efficacy over the unconjugated ("cold") rituximab alone. A planned interim
      analysis of the first 90 patients demonstrated an ORR of 80% with 90Y-ibritumomab
      tiuxetan vs 44% for rituximab (P < 0.05). To provide additional evidence of the
      benefit of 90Y radioimmunotherapy over rituximab immunotherapy, patients who were
      nonresponsive or refractory to rituximab were enrolled in an additional trial and
      treated with 90Y-ibritumomab tiuxetan 0.4 mCi/kg. An ORR of 46% was achieved in
      these rituximab-refractory patients. These results provide further evidence of
      the added value of 90Y. Therefore 90Y-ibritumomab tiuxetan radioimmunotherapy is
      a useful new treatment modality for patients with B cell NHL. Future trials are
      needed to define the optimal time in the disease course when this modality should
      be used.

PMID- 11587376
TI  - Transport of intracellularly active ribozymes to the cytoplasm.
AB  - Ribozymes are RNA molecules with enzymatic activity which selectively bind and
      cleave specific target RNAs. To date, numerous studies directed toward the
      application of ribozymes in vivo have been performed and many successful
      experiments have been reported. However, to induce high-level activities of
      ribozymes in vivo, several factors must be considered. Here we report that the
      cytoplasmic localization of ribozymes is important for their intracellular
      activity in mammalian cells. Northern blot analysis revealed that a tRNA(Val)
      ribozyme, which can assume a cloverleaf structure similar to that of a native
      tRNA, is efficiently transported to the cytoplasm. In contrast, the tRNAiMet
      driven ribozyme, which does not maintain the cloverleaf structure, remained
      predominantly in the nucleus. In correlation with the localization, the activity
      of the exported ribozyme was higher than that of the ribozyme retained in the
      nucleus. These results should provide insight into the design of ribozymes that
      have high-level activity in mammalian cells.

PMID- 11587377
TI  - Unilateral parenchymal haemorrhagic infarction in the preterm infant.
AB  - A unilateral parenchymal haemorrhage associated with a germinal matrix
      intraventricular haemorrhage (GMH-IVH) is still an important problem in the
      preterm infant and especially in those who are very immature. This type of lesion
      is now considered mainly to be caused by impaired drainage of the veins in the
      periventricular white matter and is often referred to as a venous infarction. The
      risk factors and neonatal imaging findings, as well as neurodevelopmental outcome
      and imaging data in infancy, of this type of lesion differ from those found in
      children with bilateral periventricular leukomalacia. An effort should,
      therefore, always be made to make a distinction between these two types of
      lesions. In our experience it is possible to make this distinction in most cases,
      when performing both sequential ultrasonography as well as selective magnetic
      resonance imaging during the neonatal period.

PMID- 11587378
TI  - Alexander disease and intermediate filaments in astrocytes: a fatal gain of
      function.

PMID- 11587379
TI  - The prognostic value of serial EEG recordings following acute neonatal asphyxia
      in full-term infants.
AB  - Perinatal asphyxia is one of the major causes of non-progressive neurological
      deficits seen in children. It is reported that currently no set of parameters
      allowing for accurate prediction of prognosis following severe perinatal asphyxia
      is available. Even electroencephalogram (EEG) recordings, which are known to give
      a fairly good prediction of long-term outcome, have their flaws. The aim of this
      prospective study was to evaluate the additional value of serial EEGs in full
      term infants. In all, 36 infants were enrolled. All met strict entrance criteria,
      received standard treatment and underwent two EEGs according to a pre-set
      protocol: the first between 12 and 36 hours post-partum, the second between 7 and
      9 days post-partum. It is clearly demonstrated that serial EEG recordings do
      enhance the prognostic value of the EEG. Moreover, distinct progression seen in
      serial EEGs is highly prognostic for a normal outcome and has even more
      prognostic value than one single severely abnormal EEG. A better indication of
      future outcome is obtained from serial EEGs.

PMID- 11587380
TI  - Caffeine does not affect excitotoxic brain lesions in newborn mice.
AB  - Caffeine is frequently administered to human pre-term newborns although its
      neurological impact has not been fully evaluated. In the present study performed
      in mice, we examined the effects of caffeine administration on neonatal
      excitotoxic lesions of the periventricular white matter, which mimics several
      aspects of human periventricular leukomalacia. In this model, caffeine exposure
      did not worsen white matter lesions. These data suggest that neonatal caffeine
      administration might not affect clastic lesions in pre-term infants.

PMID- 11587381
TI  - Dystonia as acute adverse reaction to cough suppressant in a 3-year-old girl.
AB  - Cough suppressant preparations containing mixtures of dextromethorphan or codeine
      with antihistamines, decongestants (sympathomimetic), expectorants and
      antipyretics with either sedative or anticholinergic activity have been
      associated with dystonic reactions in children. We report on a 3-year-old girl
      who presented with episodic stiffness and abnormal posturing with rigidity after
      arbitrary maternal administration of a mixture of methylcodeine and extract from
      Hedera plant.

PMID- 11587382
TI  - Siblings with development delay, mild spasticity and subcortical cysts: a further
      leukoencephalopathy?
AB  - We present a family with mild neurological symptoms and intra-cerebral
      subcortical cysts on magnetic resonance imaging (MRI). Common clinical features
      are microcephaly, learning difficulties, spasticity, dyspraxia and restricted
      movements of the neck and shoulder. The family has features in common with
      vacuolating leukoencephalopathy of van de Knaap and Olivier and may represent a
      new variant.

PMID- 11587383
TI  - Subdural haematoma, non-accidental head injury or ...?

PMID- 11587384
TI  - The diabetic foot.

PMID- 11587385
TI  - Transarticular stabilization for malunited fracture of the distal tibia in
      diabetics with loss of protective sensation.
AB  - Five diabetic patients who require insulin developed symptomatic malunited stress
      fracture of the distal tibia and fibula. All were treated with intramedullary
      fixation crossing the ankle joint. All progressed to stable union without
      evidence of infection. Two patients treated with antegrade intramedullary nailing
      required nail exchange for subsidence at the fracture site. One patient sustained
      a fracture at the proximal tip of a short retrograde nail, requiring replacement
      with a longer nail. Transarticular intramedullary fixation is an effective method
      of achieving stabilization for malunited fracture of the distal tibia in
      individuals with diabetes who are insensate. Due to the risk of fracture at the
      proximal tip of a standard short intramedullary nail, it is recommended to use a
      nail that extends to the proximal tibial metaphysis.

PMID- 11587386
TI  - Tissue oxygenation and skin blood flow in the diabetic foot: responses to
      cutaneous warming.
AB  - We previously reported an unexpected statistically significant decline in the
      mean transcutaneous partial pressure of oxygen (TcPO2) with cutaneous warming
      from 37 degrees C to 44 degrees C on the plantar diabetic foot, as opposed to the
      expected increase seen at the dorsal sites. To elucidate this relationship we
      compared changes with cutaneous warming in TcPO2 and skin circulation measured by
      laser Doppler flowmetry on the right plantar foot surface of 20 consecutive
      subjects. Neuropathy by monofilament testing was present in 55% of the cases.
      Right dorsal foot TcPO2 increased with cutaneous warming from 37 degrees C to 44
      degrees by a mean change of +43.6+/-20.7 mmHg (+/- standard deviation) in 95% of
      the cases. In 42% of cases right plantar first metatarsal head TcPO2 fell with
      warming from 37 degrees C to 44 degrees C by a mean change of -10.7+/-7.6 mmHg.
      In the remaining 58% of cases right plantar first metatarsal head TcPO2 rose by
      6.8+/-6.3 mmHg. In 95% of cases right plantar great toe laser Doppler perfusion
      units (LDPU) increased with warming from 36 degrees C to 44 degrees C by a mean
      change of +50.4+/-37.1. Blood flow measured by laser Doppler flowmetry increased
      in 95% of the subjects with heating. The finding that blood flow was increased
      with warming contradicts the hypothesis that arterioles in the plantar great toe
      cannot vasodilate in response to thermal stimuli. This finding supports the
      hypothesis that the decline in TcPO2 with warming might be due to an increase in
      epidermal oxygen consumption that exceeds the increase in oxygen delivery due to
      increased blood flow. The pathological mechanisms behind microvascular
      dysfunction in skin microcirculation in the diabetic foot need further
      investigation.

PMID- 11587387
TI  - Dynamic pressures on the diabetic foot.
AB  - A retrospective study was conducted in order to investigate the relation between
      increased plantar pressure and ulcers in the diabetic foot and contribute more
      information on this subject. Maximal plantar pressure (MPP) is reported on
      various areas of the plantar aspects of the feet in 328 diabetic patients and 75
      healthy subjects. An increase in MPP under all plantar areas except for the heels
      was found to be related with increasing severity of the diabetes symptoms. There
      was also a significant decrease in the application of high pressures to the
      heels, the metatarsal heads II-IV and the toes.

PMID- 11587388
TI  - Prognostic value of 99m Tc leukocyte scintigraphy in diabetic pedal
      osteomyelitis.
AB  - While leukocyte scintigraphy is accurate in detection of pedal osteomyelitis,
      there has been little data relating the technique to outcomes. We designed a
      trial to examine the prognostic value of sequential 99m Tc labeled leukocyte
      scans to establish the diagnosis of osteomyelitis and after three to four weeks
      of culture-guided antibiotic therapy. Twenty-three diabetic patients with proven
      pedal osteomyelitis (21/23) or persistent uptake (2/23) on the sequence of scans
      were studied. Five additional episodes of osteomyelitis developed in the group
      over the period of the study. Eleven patients demonstrated persistent uptake in
      the sequential scans. Nine progressed to amputation. The remaining two patients
      were biopsy-negative for infection, did not have cutaneous ulceration and were
      thought to have rapidly progressive arthropathy. Sequential leukocyte
      scintigraphy accurately predicts the need for amputation and can circumvent
      ineffective prolonged antibiotic therapy.

PMID- 11587389
TI  - Immobilization with removable walking brace for treatment of chronic foot and
      ankle pain.
AB  - Fifty feet and ankles in 47 patients (three bilateral) (26 women and 21 men;
      average age, 44+/-15 years) were treated for chronic foot and ankle pain
      (duration: minimum, three months; average, 27+/-35 months; range, three to 132
      months). Evaluation included detailed history, physical examination, and
      radiography. Initial treatment consisted of immobilization (full weight-bearing)
      using a removable walking brace (23.5 hours per day, including in bed at night),
      with standing and walking limited to activities of daily living. Follow-up
      evaluation included assessment of pain response and repeat physical examination.
      There was a history of trauma in 32 (64%) feet and ankles. Braces (pneumatic in
      31 [62%] and double-upright in 19 [38%] feet and ankles) immobilized the ankle in
      neutral position and included a rigid rocker sole. After an average of 13+/-10
      weeks (range, three to 50 weeks) of brace use, pain symptoms were improved in 35
      (70%), unchanged in 11 (22%), and worse in four (8%) feet and ankles. Physical
      examination was improved in 43 (86%) feet and ankles, unchanged in six (12%) feet
      and ankles, and worse in one (2%) foot and ankle. In all 50 feet and ankles, the
      average number of abnormal physical findings decreased from initial (6+/-3
      abnormal physical findings) to follow-up evaluation (3+/-3 abnormal physical
      findings) (P < 0.001). The average number of diagnoses per foot and ankle
      decreased from initial (4+/-1 diagnoses per foot and ankle) to follow-up
      evaluation (2+/-1 diagnoses per foot and ankle) (P < 0.0001). Improvement of pain
      was independent of duration of pre-existing symptoms, patient age, gender, or
      type of brace used. In summary, immobilization with a removable walking brace may
      improve chronic foot and ankle pain and localize the primary source of symptoms.

PMID- 11587390
TI  - Tibiotalocalcaneal arthrodesis: a biomechanical analysis of the rotational
      stability of the Biomet Ankle Arthrodesis Nail.
AB  - We hypothesized that the posterior-to-anterior (PA) calcaneal interlocking screw
      of the Biomet Ankle Arthrodesis Nail would increase rotational stability
      secondary to increased bone purchase compared with the standard lateral-to-medial
      (transverse) screw. Each of 10 fresh human cadaver lower limbs (five matched
      pairs) were stabilized with a nail inserted retrograde through the calcaneus,
      talus, and tibia according to standard technique. One limb of each pair was fixed
      with a transverse calcaneal screw; the contralateral limb, with a PA calcaneal
      screw. Each limb was then subjected to torsional testing on an MTS Mini Bionix
      load frame. The PA screw construct was significantly stiffer than the transverse
      screw construct: 1.96 and 1.41 Nm/E, respectively (P < 0.036).

PMID- 11587391
TI  - Foot care practices, services and perceptions of risk among medicare
      beneficiaries with diabetes at high and low risk for future foot complications.
AB  - A cohort of Medicare beneficiaries with diabetes was identified from inpatient
      and outpatient claims data and their risk for foot complications was estimated
      based on claims reflecting services for recent foot problems. A telephone survey
      of a random sample from this cohort was conducted to assess their foot care
      practices, barriers, and perceptions of risk. Eight percent of respondents
      reported a history of foot ulcers and 7% a history of lower extremity amputation.
      Based on claims data, 30% of respondents were at high risk for future foot
      complications. Compared to those at low risk, those at high risk were more likely
      to report having an annual foot exam, using protective footwear, and perceiving
      themselves to be high risk for future foot complications. However, 50% of those
      with claims indicating a high risk perceived themselves to be at low risk for
      future foot complications. Overall, 20% of respondents seldom checked their feet
      daily for sores or irritations. Among this group, 60% felt that it was
      unimportant and 9% reported they were limited by poor vision or physical
      problems. Our findings suggest that strategies are needed to improve the delivery
      of preventive foot care services to older persons with diabetes. Additionally,
      emphasis is needed to help individuals understand their risk and seek and perform
      appropriate preventive foot care.

PMID- 11587392
TI  - Foot and ankle survey in adults with diabetes mellitus.
AB  - The purpose of this study was to examine the foot and ankle care patterns and
      shoe wear habits in patients with clinically proven diabetes mellitus who were
      attending diabetes education classes for the first time. One hundred subjects
      were recruited from outpatient adult diabetes education classes. No attempts were
      made to select patients on the basis of disease duration or severity. Each
      subject completed a questionnaire assessing life-style, shoe wear habits, health
      care status and interaction with healthcare providers. Thirty-seven percent of
      the subjects reported prior foot problems. Twenty percent had their feet examined
      regularly and 59% had never had their feet examined. Foot problems reported were:
      corns 11%, calluses 11%, bunions 3%, ulcers 1%, gout 1%. Sensation was tested
      using the 5.07 Semmes Weinstein monofilament across seven zones of the plantar
      surface of the foot. Subjects unable to feel this varied from 5% to 20% in each
      of the zones. Shoe wear was assessed for fit and style. Thirty percent of the
      patients had shoes that were too narrow and 81% of the patients with poorly
      fitting shoes were women. Shoe wear history and factors influencing shoe
      selection were recorded. Diabetes mellitus is a common disease, often affecting
      the feet. Preventive care can help patients deal with the manifestations of
      diabetic neuropathy. This study showed that a low percentage of subjects with
      diabetes regularly have their feet examined and that a relatively high percentage
      (31%) wear shoes that are too narrow. Identifying these patients early may allow
      modification of habits that put their feet at risk.

PMID- 11587393
TI  - Development of a nurse-provided health system strategy for diabetic foot care.
AB  - A nurse-provided university health system diabetic foot
      screening/education/treatment program evaluated 403 patients in the initial 12
      months of development. All patients were provided individualized foot-specific
      patient education, varying in intensity with the magnitude of their risk status.
      One hundred and forty-five (36%) were categorized as being at risk for the
      development of a diabetic foot ulcer. Improper footwear capable of producing foot
      ulceration was recorded in 268 (66.5%) of the enrollees. Seven patients with
      previously undiagnosed Charcot foot disorder were identified. Eighty-three of the
      enrollees were seen at least once in follow-up. Sixty-one (73%) used improper
      footwear at the initial evaluation, which was decreased to 36 (43%) at the first
      follow-up visit. Nurse-provided foot-specific diabetic screening and education,
      combined with protective footwear, has been shown to be a cost- and resource
      effective method of decreasing the rate of diabetic foot ulcers, and the risk for
      eventual lower extremity amputation.

PMID- 11587394
TI  - Are North American nephrologists biased against peritoneal dialysis?
AB  - OBJECTIVE: To examine possible bias against peritoneal dialysis (PD) by
      nephrologists less familiar with it. DESIGN: Secondary analysis of a previously
      reported survey. PARTICIPANTS: All practicing Canadian nephrologists (n = 290,
      response rate 66.2%) and a subgroup of American nephrologists who were members of
      the National Kidney Foundation Council on Dialysis (n = 507, response rate
      47.3%). Responses were then subdivided by type of dialysis practice: mainly or
      only hemodialysis (HD, n = 117), mainly or only PD (n = 16), or both HD and PD (n
      = 232). INTERVENTION: Self-administered mailed questionnaire. MAIN OUTCOME
      MEASURES: Opinions and attitudes of nephrologists concerning patient
      characteristics favoring one dialysis modality over the other, as well as the
      relative utilization of HD and PD currently and in a hypothetical ideal
      situation. RESULTS: The main differences were present between physicians
      practicing mainly HD and physicians practicing mainly PD, with those practicing
      both giving answers usually intermediate to the others. The maximum weight
      suitable for PD was 10 kg less according to HD-oriented nephrologists compared
      with PD-oriented nephrologists (97.8 kg vs 108.5 kg). All nephrologists agreed
      that, ideally, 40% of prevalent end-stage renal disease patients should be on PD
      to optimize cost-effectiveness, whereas the proportion should be between 32% and
      45% when one optimizes survival, wellness, and quality of life. In general,
      differences between groups were small. CONCLUSIONS: Most nephrologists favored a
      proportion of PD higher than the current prevalence seen in either Canada or the
      U.S.A. If physicians' biases are contributing to the distribution of dialysis
      modalities, they are not likely to be major factors. Unknown but important
      factors, external to the physician, may shape modality distribution more than the
      opinions and attitudes of physicians. If a more balanced and cost-effective
      dialysis delivery system is desired, more understanding and manipulation of these
      non physician-related factors will be required.

PMID- 11587395
TI  - Degradation in peritoneal dialysis fluids may be avoided by using low pH and high
      glucose concentration.
AB  - OBJECTIVE: When glucose is present in a medical fluid, the heat applied during
      sterilization leads to degradation. The glucose degradation products (GDPs) give
      rise to bioincompatible reactions in peritoneal dialysis patients. The extent of
      the degradation depends on a number of factors, such as heating time,
      temperature, pH, glucose concentration, and catalyzing substances. In the present
      work, we investigated the influence of pH and concentration in order to determine
      how to decrease the amounts of GDPs produced. DESIGN: Glucose solutions (1%-60%
      glucose; pH 1-8) were heat sterilized at 121 degrees C. Ultraviolet (UV)
      absorption, aldehydes, pH, and inhibition of cell growth (ICG) were used as
      measures of degradation. RESULTS: Glucose degradation was minimum at an initial
      pH (prior to sterilization) of around 3.5 and at a high concentration of glucose.
      There was considerable development of acid degradation products during the
      sterilization process when the initial pH was high. Two different patterns of
      development of UV-absorbing degradation products were seen: one below pH 3.5,
      dominated by the formation of 5-hydroxy-methyl-2-furaldehyde (5-HMF); and one
      above, dominated by degradation products absorbing at 228 nm. 3-Deoxyglucosone (3
      DG) concentration and the portion of 228 nm UV absorbance not caused by 5-HMF
      were found to relate to the in vitro bioincompatibility measured as ICG; there
      was no relation between 5-HMF or absorbance at 284 nm and bioincompatibility.
      CONCLUSION: In order to minimize the development of bioincompatible GDPs in
      peritoneal dialysis fluids during heat sterilization, pH should be kept around
      3.2 and the concentration of glucose should be high. 5-HMF and 284 nm UV
      absorbance are not reliable as quality measures. 3-DG and the portion of UV
      absorbance at 228 nm caused by degradation products other than 5-HMF seem to be
      reliable indicators of bioincompatibility.

PMID- 11587396
TI  - Nutritional markers during peritoneal dialysis: data from the 1998 Peritoneal
      Dialysis Core Indicators Study.
AB  - OBJECTIVE: This analysis explores the nutritional status of adult U.S. peritoneal
      dialysis (PD) patients. DESIGN: The Peritoneal Dialysis Core Indicators Study is
      a prospective cross-sectional prevalence survey describing the care provided to a
      random sample of adult U.S. PD patients. METHODS AND POPULATION: Prevalence data
      were collected from a national random sample of 1381 adult PD patients
      participating in the United States End Stage Renal Disease (ESRD) program.
      RESULTS: The median age of these patients was 55 years, 61% were Caucasian; the
      leading cause of ESRD was diabetes mellitus. Age, sex, size, peritoneal
      permeability, dialysis adequacy, and nutritional indices did not differ between
      patients on continuous ambulatory PD and patients on automated PD. The dialysis
      prescriptions employed achieved mean weekly Kt/V urea (wKt/V) and creatinine
      clearance (wCCr) values of 2.22 +/- 0.57 and 67.8 +/- 22.5 L/1.73 m2/week,
      respectively. The PD patients were large, with a mean body weight of 77 +/- 21 kg
      and body mass index (BMI) of 27 +/- 8.6 kg/m2. The mean serum albumin of these
      patients was 3.5 +/- 0.51 g/dL, and 43% of values fell below the National Kidney
      Foundation Dialysis Outcomes Quality Initiative's desired range. The PD patients
      had a normalized protein equivalent of nitrogen appearance (nPNA) of 1.0 +/- 0.57
      g/kg/day, a normalized creatinine appearance rate (nCAR) of 17 +/- 7.3 mg/kg/day,
      and an estimated lean body mass (%LBM) of 62% +/- 18% of body weight. Serum
      albumin correlated positively with patient size, nCAR, and nPNA, but negatively
      with age, the presence of diabetes mellitus, female gender, erythropoietin dose,
      the creatinine dialysate-to-plasma ratio results of peritoneal equilibration
      testing, and the dialysis portion of the wCCr. The duration of ESRD experience
      correlated negatively with both serum albumin and patient size, although these
      relationships were complex. CONCLUSION: Peritoneal dialysis patients generally
      have marginal serum albumin levels, a finding incongruent with alternative
      measures of nutritional status, such as weight, BMI, and creatinine generation.
      Serum albumin is reduced in patients with high peritoneal permeability (i.e.,
      rapid transporters) and, because these patients generally have higher than
      average wCCr values, serum albumin is inversely correlated with the dialysis
      component of the wCCr. The presumptive nutritional indicators (BMI, %LBM, nPNA,
      and serum albumin) provide disparate estimates, varying from 10% to 50% for the
      prevalence of nutritionally stressed PD patients.

PMID- 11587397
TI  - Erectile dysfunction in chronic peritoneal dialysis patients: incidence and
      treatment with sildenafil.
AB  - OBJECTIVES: Sexual and erectile dysfunction (ED) have been reported to occur
      frequently in male patients with end-stage renal disease maintained on dialysis.
      Numerous etiologies for this ED have been suggested. Although a variety of
      therapies for the ED of the dialysis patient have been suggested, most clinicians
      indicate that patients report a poor response to therapy. Recently, sildenafil
      has been reported to be beneficial in treating patients with ED of both organic
      and psychogenic causes. The present study was designed to document the incidence
      of ED in male patients maintained on chronic peritoneal dialysis (CPD) and to
      determine the efficacy of prescribing sildenafil therapy to treat their ED.
      METHODS: All male patients in our CPD unit were notified by letter of the
      availability of sildenafil as a treatment modality for ED. A sexuality/erectile
      dysfunction assessment was conducted in all male patients by their primary
      nephrologist. Patients who reported ED and who had no medical contraindication to
      sildenafil were offered this therapy. Those patients who were interested in this
      treatment were interviewed by a social worker, and patients were asked to
      complete the International Index of Erectile Function questionnaire. Sildenafil
      was prescribed at a starting dose of 25 mg and increased to a maximum of 100 mg
      during a 12-week study trial. Patients were re-evaluated 6 and 12 weeks after the
      start of therapy. RESULTS: There were 68 male patients maintained on CPD at the
      time of the study. Mean age of all patients was 60.8 +/- 15.3 years and mean
      duration on PD was 32.6 +/- 25.6 months. Thirty-three patients had diabetes, 66
      hypertension, 35 peripheral vascular disease, and 32 coronary artery disease.
      Thirty-two of 68 male patients in the CPD unit were assessed to have ED. Only 17
      of the 32 patients expressed interest in pursuing sildenafil therapy. Two of
      these patients were excluded because they were receiving nitrate therapy. Of the
      15 patients who agreed to take sildenafil, only 6 completed the 12-week study.
      Two of these patients responded to sildenafil. CONCLUSION: Erectile dysfunction
      is common in male patients maintained on CPD. Only about half of patients with ED
      in the present study were willing to consider sildenafil therapy to treat the ED
      and, of those who agreed to treatment, only a minority completed the 12-week
      trial; 2 of these 6 patients reported a satisfactory response.

PMID- 11587398
TI  - Diverticular disease and treatment with gastric acid inhibitors do not predispose
      to peritonitis of enteric origin in peritoneal dialysis patients.
AB  - OBJECTIVE: Enteric peritonitis (EP) is an infrequent complication of peritoneal
      dialysis (PD), with severe consequences for peritoneal membrane viability and
      patient outcome. Factors such as diverticular disease and gastric acid inhibitors
      have been implicated in its appearance. We investigated several risk factors,
      including those mentioned below, that can influence the development of EP.
      DESIGN: Retrospective cross-sectional study. SETTING: Tertiary-care public
      university hospital. PATIENTS: Fifty-seven PD patients treated in our PD unit
      during August 1998. MAIN OUTCOME MEASURES: A barium enema was performed on 50 of
      the 57 patients (the remaining 7 patients refused it) in order to exclude the
      presence of diverticulosis. All episodes of peritonitis occurring in those
      patients, including EP, were registered. Enteric peritonitis was defined as that
      caused by gram-positive, gram-negative, or fungus micro-organisms that colonized
      the intestinal tract, excluding episodes secondary to genitourinary tract or
      peritoneal catheter exit-site infections. RESULTS: Twenty-four patients showed
      diverticular disease in the barium enema, but only 5 of them (21%) had any EP
      episode. Five of the 26 patients with no diverticula (19%) had EP. Fifty-five
      episodes of peritonitis were reported in 21 patients; 15 episodes of EP (27.3% of
      all) developed in 11 patients. Seven of the 11 patients (64%) required peritoneal
      catheter removal and 3 of them (27%) finally were transferred to hemodialysis due
      to consequences of the EP episode. Logistic regression analysis did not find any
      of the independent variables analyzed (age, sex, time on PD, type of PD,
      peritoneal transport parameters, presence of polycystic kidney disease,
      constipation or diverticulosis, or treatment with gastric acid inhibitors, or
      phosphate-binding agents) to be risk factors for developing EP. CONCLUSIONS:
      Neither diverticulosis nor treatment with gastric acid inhibitors seem to be risk
      factors for developing peritonitis of enteric origin in PD patients. This type of
      peritonitis has to be promptly identified and treated in order to diminish the
      high frequency of peritoneal catheter removal and PD dropout due to such
      episodes.

PMID- 11587399
TI  - Trends in CAPD technique failure: Canada, 1981-1997.
AB  - OBJECTIVE: Although important enhancements to continuous ambulatory peritoneal
      dialysis (CAPD) have occurred since its inception, few studies have explicitly
      evaluated trends over time in CAPD technique failure rates. To assist in
      quantifying the net benefit of improvements to CAPD for patient outcomes, we
      examined trends in technique failure rates among Canadian CAPD patients.
      PATIENTS: Patients initiating renal replacement therapy on CAPD (n = 7110)
      between 1981 and 1997. MAIN OUTCOME MEASURES: Technique failure (i.e., switch to
      hemodialysis). RESULTS: Total follow-up was 12,831 patient-years (pt-yr). There
      were 1976 technique failures, for a crude CAPD failure rate of 154.0/1000 pt-yr.
      Technique failure rate ratios (RR) estimated using Poisson regression and
      adjusted for age, gender, race, province, primary renal diagnosis, and follow-up
      time, were significantly reduced for the 1990-93 [RR = 0.75, 95% confidence
      interval (CI) = (0.68, 0.83)], 1994-95 [RR = 0.83, CI (0.75, 0.93)], and 1996-97
      [RR = 0.78, CI (0.70, 0.87)] calendar periods relative to 1981-89 (RR = 1,
      reference). Among cause-specific technique failure rates, the greatest
      improvement was observed for peritonitis-attributable technique failure, with RR
      = 0.46, CI (0.41, 0.50) for 1990-97 relative to 1981-89. However, rates of
      technique failure due to inadequate dialysis were significantly elevated for the
      1990-97 period [RR = 1.68, CI (1.44, 1.96)]. CONCLUSIONS: The collection of more
      detailed data on practice patterns would enable future studies to elucidate the
      cause-and-effect relationship between CAPD descriptors and technique failure, and
      hence assist in clinical decision-making.

PMID- 11587400
TI  - Azithromycin: an assessment of its pharmacokinetics and therapeutic potential in
      CAPD.
AB  - BACKGROUND: Azithromycin is an azalide antibiotic with a similar antibacterial
      spectrum to erythromycin but with greater gram-negative activity. Azithromycin
      displays a favorable pharmacokinetic profile, with improved absorption and higher
      sustained tissue concentrations compared with erythromycin. This results in a
      prolonged elimination half-life, suggesting a potential for treating continuous
      ambulatory peritoneal dialysis (CAPD) peritonitis. OBJECTIVE: This study aimed to
      define the potential role of azithromycin in treating CAPD peritonitis. DESIGN:
      The pharmacokinetics and peritoneal dialysis (PD) clearance of azithromycin were
      studied following a single 500-mg oral dose of azithromycin. Blood and dialysate
      samples were taken over a 10-day period and assayed using high-pressure liquid
      chromatography. SETTING: The study took place within the Renal Unit at Southend
      Hospital NHS Trust, a district general hospital in the United Kingdom. PATIENTS:
      Eight patients with oliguric end-stage renal failure without peritonitis
      maintained on CAPD (3 x 2 L/day). RESULTS: Peak plasma concentrations occurred at
      2-3 hours with 0.35-1.35 microg/mL (mean 0.75). The mean elimination half-life
      was 84.55 hrs, and plasma clearance was 21.93 L/hour. This compares with values
      of greater than 40 hours and 40.8 L/hour reported in healthy volunteers. After 8
      hours, the mean dialysate concentration was 0.07 microg/mL; PD clearance was 0.06
      L/hr. CONCLUSION: Azithromycin is not substantially removed by CAPD in the
      absence of peritonitis and cannot be recommended for widespread use in this
      setting at present. However, the successful use of azithromycin in CAPD
      peritonitis, due possibly to an intracellular drug transport mechanism, has been
      reported. Future research should address this possibility.

PMID- 11587401
TI  - Intravenous vancomycin pharmacokinetics in automated peritoneal dialysis
      patients.
AB  - The pharmacokinetics of intravenous (i.v.) vancomycin was studied in automated
      peritoneal dialysis (APD) patients who received a single i.v. dose of vancomycin
      (15 mg/kg total body weight). Dialysate samples were collected at the beginning,
      middle, and end of dwells 1-3 (on-cycler), and at the end of dwells 4 and 5 (off
      cycler), for a 24-hour period. Blood samples were collected at the beginning,
      middle, and end of dwells 1-3 (on-cycler), and at the end of dwell 5 (off-cycler)
      for a 24-hr period. Pharmacokinetics parameters were calculated assuming a one
      compartment model. Glomerular filtration rate (GFR) and vancomycin clearance (CI)
      values were normalized to 1.73 m2. Ten patients [4 males, 6 females; 47.4 +/- 9.9
      years of age (mean +/- SD)] who had received PD for a median 3.5 months (range 2
      66 months) were studied. Dwell times were 2.3 +/- 0.1 hours on cycler and 7.3 +/-
      0.1 hours off cycler. Vancomycin half-life was significantly different on-cycler
      than off-cycler (11.6 +/- 5.2 hr vs 62.8 +/- 33.0 hr; p < 0.001). Vancomycin
      total CI (CI(T)) was 7.4 +/- 2.0 mL/min. Renal CI (CI(R)) and PD CI (CI(PD))
      accounted for 23.6% and 28.0% of CI(T). respectively. CI(R) correlated with GFR
      (CI(R) = 0.90 GFR - 1.01; r2 = 0.79; p = 0.008). Mean vancomycin serum and
      dialysate end-of-dwell concentrations were above minimum inhibitory concentration
      of susceptible organisms (5 micro/mL) for the first cycler and the second
      ambulatory exchanges only. The results of this study suggest that, to provide
      adequate concentrations for susceptible organisms over a 24-hour period, current
      intermittent vancomycin dosing recommendations for PD-related peritonitis need to
      be changed to 35 mg/kg intraperitoneally on day 1, then 15 mg/kg i.p. thereafter
      (i.e., once daily) in APD patients.

PMID- 11587402
TI  - Effective treatment of peritoneal dialysis-associated peritonitis with cefazolin
      and ceftazidime in children.
AB  - OBJECTIVE: To evaluate the use of the combination of cefazolin and ceftazidime
      for initial treatment of peritoneal dialysis (PD)-related peritonitis in
      pediatric patients. DESIGN: Retrospective nonrandomized study. SETTING: Pediatric
      dialysis units of the University Medical Center of Utrecht and Nijmegen, The
      Netherlands. PATIENTS: 40 children (median age 5.4 years) who were treated with
      PD during the study period of 4.5 years. INTERVENTIONS: All 50 episodes of
      peritonitis that occurred during the study period were evaluated by review of
      medical records. Patients were given intraperitoneal ceftazidime 500 mg/L
      dialysis fluid, and cefazolin 500 mg/L as a loading dose, followed by a
      maintenance dose of ceftazidime 125 mg/L and cefazolin 100 mg/L,
      intraperitoneally, 4 times daily. Antibiotics were continued for 14 days.
      RESULTS: After identification of the causative microorganism, one of the
      antibiotics was discontinued in 34 cases, and the antibiotic schedule was adapted
      in 2 cases. All cases were initially cured within 3 days. In 5 cases (10%), there
      was a peritonitis with the same organism recurring within 2 weeks after
      completion of treatment. There were 4 cases of PD-related peritonitis caused by
      pseudomonas, all of which were cured. CONCLUSIONS: The antibiotic combination of
      cefazolin and ceftazidime is effective for the initial therapy of PD-related
      peritonitis in children. The toxic complications of aminoglycosides are avoided
      with this combination.

PMID- 11587403
TI  - Peritoneal dialysis for management of pediatric acute renal failure.
AB  - BACKGROUND: While the use of continuous renal replacement therapies in the
      management of children with acute renal failure (ARF) has increased, the role of
      peritoneal dialysis (PD) in the treatment of pediatric ARF has received less
      attention. DESIGN: Retrospective database review of children requiring PD for ARF
      over a 10-year period. SETTING: Pediatric intensive care unit at a tertiary-care
      referral center. PATIENTS: Sixty-three children without previously known
      underlying renal disease who required PD for treatment of ARF. RESULTS: Causes of
      ARF were congestive heart failure (27), hemolytic-uremic syndrome (13), sepsis
      (10), nonrenal organ transplant (7), malignancy (3), and other (3). Mean duration
      of PD was 11 +/- 13 days. Children with ARF were younger (30 +/- 48 months vs 88
      +/- 68 months old, p < 0.0001) and smaller (11.9 +/- 15.9 kg vs 28 +/- 22 kg, p <
      0.0001) than children with known underlying renal disease who began PD during the
      same time period. Percutaneously placed PD catheters were used in 62% of children
      with ARF, compared to 4% of children with known renal disease (p < 0.0001).
      Hypotension was common in patients with ARF (46%), which correlated with a high
      frequency of vasopressor use (78%) at the time of initiation of PD. Complications
      of PD occurred in 25% of patients, the most common being catheter malfunction.
      Recovery of renal function occurred in 38% of patients; patient survival was 51%.
      CONCLUSIONS: Peritoneal dialysis remains an appropriate therapy for pediatric ARF
      from many causes, even in severely ill children requiring vasopressor support.
      Such children can be cared for without the use of more expensive and technology
      dependent forms of renal replacement therapies.

PMID- 11587404
TI  - Impact of dialysis adequacy on cardiac function in pediatric CAPD patients.
AB  - BACKGROUND: Left ventricular hypertrophy is a major cause of morbidity and
      mortality among patients with chronic renal failure. Uremia-related risk factors
      play a fundamental role in its occurrence, thus better prognosis and prolonged
      survival can be attained by successful dialytic therapies. OBJECTIVE: To
      investigate whether dialysis adequacy has a beneficial effect on cardiac
      structure and function in children receiving continuous ambulatory peritoneal
      dialysis (CAPD). DESIGN: Cross-sectional study in the Pediatric Peritoneal
      Dialysis Unit of a university hospital. PATIENTS: Eighteen children, aged 13.3 +/
      2.8 years, being treated with CAPD, and 20 healthy age- and sex-matched control
      subjects were enrolled in this study. MAIN OUTCOME MEASURES: Echocardiographic
      evaluation was performed in all subjects. Dialysis adequacy indices [weekly urea
      (Kt/V) and creatinine clearance (TCCr)] were calculated in the dialysis group.
      RESULTS: Interventricular septal thickness, left ventricular (LV) posterior wall
      thickness, LV mass index (LVMI), and LV end systolic and diastolic dimensions
      were all found to be significantly higher in the CAPD group compared to the
      control subjects (p < 0.01). Ejection fraction and fractional shortening of the
      LV were not significantly different between the two groups. Mean Kt/V was 2.02 +/
      0.71 and mean TCCr was 58 +/- 33 L/wk/1.73 m2. There were significant negative
      correlations between dialysis adequacy indices and LV end systolic and diastolic
      dimensions (p < 0.05 and p < 0.001). Ejection fraction and fractional shortening
      were positively correlated with Kt/V (p < 0.01). Systolic and diastolic blood
      pressures were positively correlated with LVMI (r= 0.501 and r = 0.523).
      Significant inverse correlations between mean arterial pressure and both Kt/V and
      TCCr (r = -0.555 and r = -0.520) were detected. CONCLUSION: These data clearly
      document that cardiac structure and function are remarkably influenced by the
      uremic state and dialysis therapy in pediatric CAPD patients. The close
      relationships between echocardiographic findings and dialysis adequacy indices
      suggest that adequate dialysis has a beneficial effect on cardiac function via
      effective removal of toxic substances.

PMID- 11587405
TI  - Pediatric peritoneal dialysis training: characteristics and impact on peritonitis
      rates.
AB  - OBJECTIVE: Peritonitis is the leading cause of technique failure in pediatric
      patients on peritoneal dialysis. A survey was developed to determine what impact,
      if any, training practices and staffing patterns have on peritonitis rates in
      pediatric patients. DESIGN: A survey developed by the International Society for
      Peritoneal Dialysis Advisory Committee on Peritonitis Management in Pediatric
      Patients. PATIENTS: The survey was distributed to 168 centers and was completed
      by 76 (45%) centers. A total of 597 children younger than 21 years of age
      received peritoneal dialysis in these centers. RESULTS: The peritonitis rate was
      significantly lower (1 episode/19.9 months vs 1 episode/13.5 months; p < 0.05) in
      programs characterized by larger patient numbers (> or = 15 patients vs < 15
      patients) and longer training time dedicated to theory and practical/technical
      skills (p < 0.01). CONCLUSION: Peritoneal dialysis training is an important
      factor that influences the rate of peritonitis. The results of this survey
      reinforce the value of the time committed to this effort.

PMID- 11587406
TI  - Late renal transplant failure: an adverse prognostic factor at initiation of
      peritoneal dialysis.
AB  - BACKGROUND: Early renal transplant failure necessitating a return to dialysis has
      been shown to be a poor prognostic factor for survival. Little is known about the
      outcome of patients with late transplant failure returning to dialysis. It was
      our clinical impression that late transplant failure (>2 months) carries an
      increased morbidity and mortality risk in patients returning to dialysis.
      OBJECTIVE: To determine whether patients with a failed renal transplant have an
      outcome different to those on dialysis who have never received a kidney
      transplant. SETTING: Peritoneal dialysis (PD) unit in a teaching hospital.
      PATIENTS AND DESIGN: All failed renal transplant patients (fTx) in the Toronto
      Hospital Peritoneal Dialysis program between 1989 and 1996 were identified. This
      cohort of 42 fTx patients was compared with a cohort of randomly selected never
      transplanted PD patients (non-Tx). The PD program was selected because of the
      availability of well-documented patient archival material. The non-Tx group was
      matched for age and presence of diabetes. Data were collected until
      retransplantation, change of dialysis modality or center, death, or until June
      1998. RESULTS: There was no difference at initiation of PD between groups in
      serum albumin, residual renal function, or mean serum parathyroid hormone level.
      The mean low-density lipoprotein level was significantly higher in the fTx
      cohort. The duration of dialysis before Tx in fTx patients accounted for the
      increased total length of dialysis in fTx (mean 15 months). However, post-Tx the
      duration of PD was similar for both groups (30.7 months for fTx vs 31.6 months
      for non-Tx). The fTx group had a considerably worse outcome than the non-Tx
      group. The time to first peritonitis, subsequent episodes of peritonitis,
      catheter change, or transfer to hemodialysis occurred at a much faster rate in
      fTx patients. The most dramatic difference was in survival. There were 3 deaths
      in the non-Tx group and 12 in the fTx group (p < 0.01). The mean age at time of
      death in the fTx group was 47.5 years. Deaths were due mainly to gram-negative
      peritonitis and cardiovascular disease. CONCLUSIONS: We conclude that late failed
      renal transplant patients starting dialysis are at increased risk of
      complications and have strikingly higher mortality rates than non-Tx patients. A
      previously failed kidney transplant can be considered an adverse prognostic
      factor for patients commencing PD; these patients need to be closely monitored.
      Although this study was limited to PD patients, the same principles likely apply
      to fTx patients returning to any form of renal replacement therapy.

PMID- 11587407
TI  - Peritoneal dialysis following failed kidney transplantation is associated with
      high peritoneal transport rates.

PMID- 11587408
TI  - A case of sterile peritonitis associated with icodextrin solution.

PMID- 11587409
TI  - Delusion of worm infestation associated with clarithromycin in a patient on
      peritoneal dialysis.

PMID- 11587410
TI  - Asymptomatic tuberculous peritonitis in a CAPD patient.

PMID- 11587411
TI  - Inflammation and gross vascular alterations are characteristic histological
      features of sclerosing peritonitis.

PMID- 11587412
TI  - Postoperative exit-site infection and factors affecting it.

PMID- 11587413
TI  - Hypercalcemia in a peritoneal dialysis patient.

PMID- 11587414
TI  - Literature: July-August 2001.

PMID- 11587415
TI  - Effects of the routine change of chronic indwelling Foley catheters in persons
      with spinal cord injury.
AB  - OBJECTIVE: To determine whether routine catheter changes have any effect on the
      urinary white blood cell count (WBC) and bacterial culture in asymptomatic
      individuals with spinal cord injury (SCI) who have indwelling Foley catheters.
      DESIGN: Prospective case series. SETTING: Urology and SCI outpatient departments
      of a rehabilitation center. SUBJECTS: Twelve asymptomatic individuals (male and
      female) with SCI who have chronic indwelling urethral Foley catheters that are
      changed routinely every month. MAIN OUTCOME MEASURES: Two sets of urinalysis and
      urinary culture and sensitivity from each individual, one set taken through the
      Foley catheter before the catheter change and another set after the catheter
      change. WBC, bacterial identity, and colony count were measured, and the
      corresponding data were compared. RESULTS: All subjects had pyuria and
      bacteriuria before and after the catheter change. Analysis of the data showed a
      statistically significant increase in WBC in the urine after the indwelling Foley
      catheter was changed (P = .0039). However, bacterial types and corresponding
      colony counts remained almost completely unchanged. CONCLUSIONS: Routine change
      of chronic indwelling Foley catheters in asymptomatic individuals with SCI causes
      a significant rise in the urinary WBC, without altering the bacterial identity or
      colony count. Pyuria and bacteriuria are prevalent among individuals with SCI
      (including those who are asymptomatic) with indwelling Foley catheters. This
      study suggests that urinalysis should be taken before a catheter change.

PMID- 11587416
TI  - A method to minimize indwelling catheter calcification and bladder stones in
      individuals with spinal cord injury.
AB  - Indwelling catheters are a common tool of bladder management in persons with high
      level spinal cord injury who are unable to intermittently catheterize their
      bladders. Indwelling catheters are used to prevent bladder overdistension, which
      can trigger autonomic dysreflexia in those with injuries at or above T6.
      Unfortunately, indwelling catheters are prone to encrustation and can lead to the
      formation of bladder stones that can block the catheter and cause autonomic
      dysreflexia. We found that weekly catheter changes dramatically reduced catheter
      encrustation and stones in 2 individuals who had a history of recurrent stones
      despite various accepted interventions. We describe the clinical course and
      impact of this method in each case.

PMID- 11587417
TI  - A neuroprosthesis for high tetraplegia.
AB  - BACKGROUND: This case report describes a neuroprosthesis that restored shoulder
      and elbow function in a 23-year-old man with chronic C3 complete tetraplegia.
      Before implementation of the neuroprosthesis, electrodiagnostic testing revealed
      denervation from C5 to T1, with the greatest degree of denervation in the C8 and
      T1 myotomes. Thirteen percutaneous intramuscular electrodes were implanted into
      muscles acting on the shoulder and elbow of one upper limb. Before functional
      testing, the subject underwent a conditioning regimen to maximize the strength
      and endurance of the implanted muscles. RESULTS: After completion of the 8-week
      exercise regimen, stimulated active range of motion against gravity included 60
      degrees of shoulder abduction, 45 degrees of shoulder flexion, 10 degrees of
      shoulder external rotation with the shoulder passively abducted to 90 degrees,
      and 110 degrees of elbow flexion. Stimulated elbow extension lacked 20 degrees of
      full extension with gravity eliminated. After system setup, the subject was able
      to pick up mashed potatoes on a plate with a utensil and bring them to his mouth
      using the neuroprosthesis and a balanced forearm orthosis. A switch mounted on
      the headrest of the subject's wheelchair and a position sensor mounted on the
      contralateral shoulder allowed the subject to control movement of his upper limb.

PMID- 11587418
TI  - Acute transverse myelitis in a 7-month-old boy.
AB  - Acute transverse myelitis (ATM) is an acute intramedullary spinal cord disease
      characterized by an abrupt onset of rapidly progressive weakness of the
      extremities accompanied by a loss of sensation and sphincter control. Although
      ATM has an important place in childhood spinal cord disorders, its occurrence
      remains extremely uncommon in the infant population (0 to 12 months old). This
      report of a 7-month-old boy with ATM is followed by a discussion of the case and
      review of the literature regarding etiology, diagnosis, and prognosis for
      neurological recovery.

PMID- 11587419
TI  - Refractory heterotopic ossification with complications.
AB  - BACKGROUND: Heterotopic ossification (HO) following spinal cord injury can lead
      to various complications, including venous thrombosis, autonomic dysreflexia, and
      pressure ulcers. We report refractory, complicated HO in a 19-year-old man with
      C8 incomplete tetraplegia. He first presented at 9 weeks postinjury with fever
      and swelling of his right leg. Ultrasound indicated a deep venous thrombosis
      (DVT). Persistent symptoms prompted triple-phase bone scan and magnetic resonance
      imaging (MRI), which revealed HO compressing the right external iliac vein and no
      evidence of DVT. The HO was complicated by hypercoagulability. CLINICAL COURSE:
      The HO was refractory to oral indomethacin and etidronate; therefore, intravenous
      etidronate was instituted, resulting in only a transient decrease in alkaline
      phosphatase. Local irradiation of the right hip did not decrease the activity of
      HO. The patient was discharged on oral etidronate, indomethacin, and warfarin.
      This complicated case raises issues regarding early diagnosis and aggressive
      treatment of HO, as well as treatment of associated hypercoagulability.

PMID- 11587420
TI  - Spinal cord injury caused by gunshot wound during pregnancy.
AB  - We report a case of a pregnant woman with acute spinal cord injury (C5) caused by
      gunshot wound and discuss the respective maternal and fetal considerations.
      Neither decompressive surgery nor corticosteroid protocols were used. At 37
      weeks, the patient delivered a normal female infant after induction of labor and
      epidural anesthesia, with no medical or obstetrical complications. With
      conservative management and rehabilitation, this patient had significant recovery
      of function.

PMID- 11587421
TI  - Spinal cord injury medicine: meeting the challenges of a growing subspecialty.

PMID- 11587422
TI  - Acute effects of locomotor training on overground walking speed and H-reflex
      modulation in individuals with incomplete spinal cord injury.
AB  - OBJECTIVE: The purpose of this study was to assess the effect of a single bout of
      a locomotor-training paradigm on overground walking speed and H-reflex modulation
      of individuals with incomplete spinal cord injury (SCI). METHODS: Self-selected
      and maximum walking speeds and soleus H-reflexes (H/M ratios) during standing and
      stance and swing phases of walking (self-selected velocity) were obtained from 4
      individuals with American Spinal Injury Association impairment classification D.
      Data were collected immediately before and after a single bout of locomotor
      training with body weight support on a treadmill. The pretraining H/M ratios of
      the SCI subjects were also compared with values from 4 able-bodied subjects who
      did not receive the intervention. Maximum H/M ratios while standing and during
      midstance and midswing phases of overground walking were considerably greater in
      the SCI subjects than in the control subjects. RESULTS: After the single bout of
      training, self-selected and maximum overground walking speeds of the subjects
      with SCI increased by 26% and 25%, respectively. Furthermore, H-reflexes were
      significantly more depressed in the SCI subjects during overground walking (28%
      less during stance, 34% less during swing). CONCLUSIONS: Although preliminary,
      these findings indicate that a single bout of locomotor training produced
      immediate increases in walking velocity and acute neurophysiologic changes in
      individuals with incomplete SCI.

PMID- 11587423
TI  - Levels of plasma homocysteine in persons with spinal cord injury.
AB  - BACKGROUND: Premature coronary vascular disease is a leading cause of morbidity
      and mortality in persons with chronic spinal cord injury (SCI). Evidence
      indicates that an elevated plasma homocysteine level is an independent risk
      factor for vascular disease. METHODS: Plasma homocysteine levels were collected
      in 845 subjects with SCI and compared to those in a reference population.
      Differences in plasma homocysteine were determined for sex, race/ethnicity,
      neurological deficit, and age, as well as for serum creatinine concentration.
      RESULTS: Plasma homocysteine was significantly higher in men than in women. Men
      were more likely to have moderately or severely elevated plasma homocysteine
      levels. Stratifying by male sex, greater percentages of whites and African
      Americans had severely elevated plasma homocysteine levels (>20 micromol/L)
      compared with Latinos (12% and 14% versus 8%; P > .01). For the total group with
      SCI, plasma homocysteine levels were not significantly different by
      race/ethnicity or neurological deficit subgroup. For the total group (P < .05)
      and within each sex (men, P < .05; women, P < .01), the older age group with SCI
      (>50 years) had significantly higher mean plasma homocysteine levels than the
      younger age group. Age was positively related to plasma homocysteine levels in
      men (P < .05) and women (P < .01). Plasma homocysteine levels were higher among
      men for any given age than among women (P < .0001) by an average of 3.19 +/- 0.51
      micromol/L. Regardless of age or sex, persons with SCI tended to have higher
      levels of plasma homocysteine than able-bodied persons matched for age and sex.
      CONCLUSION: Because the risk of a vascular event increases with age, elevated
      levels of plasma homocysteine place older persons with SCI at further increased
      risk for a vaso-occlusive event. Of note, there was a stepwise increase in plasma
      homocysteine concentration for each quartile of higher serum creatinine
      concentration. Patients who have elevated levels of plasma homocysteine should
      receive a trial course of daily supplementation with oral folic acid and vitamin
      B12. If that is ineffective, they should receive vitamin B6 supplementation to
      lower their plasma homocysteine levels.

PMID- 11587425
TI  - Cancer of the prostate in myelopathy patients: lower risk with higher levels of
      paralysis.
AB  - PURPOSE: The prevalence of cancer of the prostate (CAP) among patients with
      myelopathy is lower among the more severely paralyzed. The objective of this
      study was to determine whether this phenomenon could be more precisely defined.
      METHODS: Men 50 years of age or older who were registered with the spinal cord
      injury (SCI) service of the Department of Veterans Affairs Medical Center (West
      Roxbury, Massachusetts) in 1989 were classified by level and grade of paralysis.
      Cases of CAP were identified by review of the hospital tumor registry and
      autopsies over the ensuing 11 years. The difference in the incidence of CAP
      between patients with high and low levels of paralysis was tested by comparison
      of proportions. RESULTS: Eight cases of CAP were found in 2594 patient-years of
      follow-up. CAP developed in 3 of 218 patients paralyzed at C2 to T10 and in 5 of
      60 patients paralyzed at T11 to S2. Incidence rates were 0.15 versus 0.91 per 100
      patient-years, respectively (P = .015). When patients with incomplete paralysis
      were excluded, the incidence rates were 0 and 2.1 per 100 patient-years for the
      higher and lower lesions, respectively (P < .001). CONCLUSION: The incidence of
      CAP is lower in myelopathy patients with higher levels of paralysis (T10 or
      above) than in those with lesions at T11 or below.

PMID- 11587424
TI  - Impact of demographic and medical factors on satisfaction with life after spinal
      cord injury: a normative study.
AB  - OBJECTIVE: The aim of this study was (1) to examine demographic and medical
      predictors of the Satisfaction With Life Scale (SWLS) among individuals with
      spinal cord injury (SCI) and (2) to provide a normative table for the SWLS that
      includes appropriate adjustments for the most important predictors of life
      satisfaction. STUDY DESIGN: We examined predictors of the SWLS including age,
      education, sex, race, injury duration, number of rehospitalizations, marital
      status, employment status, SCI etiology, and level of neurological impairment.
      PARTICIPANTS: Individuals in the National Spinal Cord Injury Statistical Center
      database [from 18 SCI model systems (1995-1999)] undergoing follow-up assessment
      were included for study. OUTCOME MEASURE: Satisfaction With Life Scale. RESULTS:
      Univariate analyses indicated that marital and employment status, race, sex,
      education, and injury duration were significant factors associated with scores on
      the SWLS. In general, individuals who were female, white, married, and currently
      employed and had a higher education and longer injury duration reported
      significantly higher scores on the SWLS (P < .01). Effect-size estimates for
      these factors ranged from 0.16 to 0.41. Regression analyses showed that
      education, employment status, and injury duration were the strongest unique
      predictors of satisfaction with life but accounted for only 10% of the variance.
      CONCLUSION: The SWLS is a global measure of life satisfaction and is relatively
      unrelated to demographic and medical characteristics. Normative tables are
      provided for epidemiologic comparison.

PMID- 11587427
TI  - Clinical research: establishing our priorities.

PMID- 11587426
TI  - Bacteremia after spinal cord injury in initial versus subsequent
      hospitalizations.
AB  - BACKGROUND: Individuals with spinal cord injury (SCI) have a high lifelong risk
      for systemic infection. For optimal therapy, it is important to characterize the
      organisms involved in bacteremic episodes and the sites of primary infection. The
      increase in drug-resistant bacteria in recent years underscores the importance of
      gathering accurate microbiological information. METHODS: We performed a
      retrospective study of hospitalized people with SCI using a computerized
      Microbiology Laboratory Database. We compared the microbiology of bacteremic
      episodes during initial versus unplanned subsequent hospitalizations. Data were
      collected on 55 bacteremic episodes in 30 people during initial hospitalization
      for SCI and 50 episodes in 29 people who were rehospitalized. RESULTS: Among
      cases in which a site of origin could be identified, the respiratory tract was
      the origin of the majority of bacteremias during initial hospitalizations, and
      the urinary tract was the primary origin during rehospitalizations. Polymicrobial
      bacteremia occurred in 14 of 55 (25%) initial versus 14 of 50 (28%) subsequent
      hospitalization episodes. The most common pathogens were coagulase-negative
      staphylococci, followed by Staphylococcus aureus and Enterobacteriaceae.
      Bacteremia was more common in people with tetraplegia and complete neurologic
      lesions than in those with paraplegia and incomplete lesions. One person in the
      rehospitalization group died from complications of bacteremia. All others were
      successfully treated. CONCLUSIONS: This study describes the frequency and
      characteristics of bacteremia during initial and subsequent hospitalizations
      following SCI and examines differences in original sites of infection. This
      information should be considered when planning infection control measures and
      empiric antibiotic regimens for patients with SCI.

PMID- 11587428
TI  - Modes, benefits, and risks of voluntary an delectrically induced exercise in
      persons with spinal cord injury.
AB  - BACKGROUND: Sedentary lifestyles and physical deconditioning are commonly
      reported among persons with spinal cord injury (SCI), although many forms of
      exercise have been shown to be beneficial. For individuals unable to perform
      voluntary exercise, involuntary exercise by electrically stimulated contractions
      has been used to train individual body segments, invoke cycling movements with or
      without arm propulsion, and stimulate ambulation. OBJECTIVE: To evaluate the
      benefits and risks associated with various modes of exercise in persons with SCI.
      METHODS: Literature review. FINDINGS: Electrical stimulation of local muscle
      sites increases muscle mass and circulation and favorably alters muscle fiber
      composition. Electrically stimulated cycling has been observed to improve
      fitness, lower-extremity circulation, and circulatory response to ischemia and to
      reverse cardiac muscle atrophy in persons with tetraplegia. Electrically
      stimulated ambulation improves upper-extremity endurance, lower-extremity
      circulation, and perception of body image. Studies of arm and wheelchair
      ergometry show increased arm endurance and decreased cardiovascular risks
      associated with hyperlipidemia, while resistance training of the upper
      extremities improves strength and endurance. Because autonomic hyperreflexia,
      orthostatic intolerance, thermal dysregulation, and fracture are associated with
      exercise in SCI, risk reduction strategies and prompt intervention are required.
      CONCLUSIONS: Well-designed programs of exercise are beneficial for persons with
      tetraplegia and paraplegia. Risks and benefits vary with level of injury.
      Programs need to address prevention of and intervention for potential adverse
      effects associated with exercise in individuals with spinal cord dysfunction.

PMID- 11587429
TI  - Relationship between EMG and muscle force after spinal cord injury.
AB  - OBJECTIVE: The purpose of this study was to compare the electromyography (EMG)
      score during contraction of a given muscle to the independently measured manual
      muscle test (MMT) score for that same muscle (or muscle group), to determine
      whether EMG measures could serve as a reasonable approximation of muscle
      contraction force in persons with acute spinal cord injury (SCI). METHODS: We
      examined the strength of relationship between surface-recorded EMG and estimated
      muscle strength using the MMT in a population of 45 subjects with acute (<1 week)
      traumatic SCI. Eight different muscle groups were compared in each individual;
      measures were repeated on these subjects approximately 2 months later. A 6-point
      numeric index was used for assignment of EMG scores, all of which were done in a
      blinded fashion by 1 investigator from tape-recorded evaluations. RESULTS: Nearly
      all of the individual muscle comparisons led to positive and significant (P <
      .01) correlations between EMG and MMT scores, at both the acute and subacute time
      points following injury. CONCLUSIONS: These findings support the use of EMG
      scoring as an indicator of recovery of volitional strength following SCI in a
      given subject. However, caution must be used when attempting to extrapolate EMG
      scores to absolute forces or when comparing EMG scores among different subjects.

PMID- 11587430
TI  - Circuit resistance training improves the atherogenic lipid profiles of persons
      with chronic paraplegia.
AB  - BACKGROUND: People with chronic paraplegia frequently experience dyslipidemias
      characterized by depressed levels of high-density lipoprotein cholesterol (HDL-C)
      and elevated levels of low-density lipoprotein cholesterol (LDL-C). These
      abnormal lipid profiles and poor fitness levels increase their risk for
      cardiovascular disease. METHODS: To test the hypothesis that circuit resistance
      exercise training improves both upper-extremity fitness and the atherogenic lipid
      profile in persons with chronic paraplegia, a homogeneous cohort of 5 men with
      neurologically complete spinal cord injuries at T6 to L1 underwent 3 months of
      exercise training using uninterrupted resistance and endurance exercises of the
      upper extremities. Training was performed 3 times a week on alternating days.
      RESULTS: Results of graded arm exercise testing showed a 30.3% improvement in
      peak oxygen consumption (P < .01), a 33.5% increase in time to fatigue (P < .01)
      and a 30.4% increase in peak power output (P < .05). Pretraining total
      cholesterol levels (TC) were in the low-risk category and were nonsignificantly
      lowered following training. Similar nonsignificant reductions of plasma
      triglycerides averaging 12 mg/dL were attained. Conversely, a 25.9% lowering of
      LDL-C (P < .05) and 9.8% elevation of HDL-C (P < .05) were observed after
      training. These changes reduced the average LDL-C-to-HDL-C ratio by 1 unit (P <
      .05) and the TC-to-HDL-C ratio from 5.0 +/- 1.1 (mean +/- SD) to 3.9 +/- 0.7 (P <
      .05). CONCLUSIONS: This change reflects a cardiovascular risk reduction of almost
      25%; the TC/HDL-C declined from the high-risk score of 5.0 to near the desired
      score of 3.5. These findings support the beneficial effects of circuit exercise
      resistance training on fitness and atherogenic lipid profiles in persons with
      chronic paraplegia.

PMID- 11587431
TI  - The effect of dietary intervention on lipid profiles in individuals with spinal
      cord injury.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of a simple
      dietary intervention for individuals with chronic spinal cord injury (SCI) and
      moderately elevated total cholesterol. METHODS: Baseline and follow-up serum
      lipid values were obtained on 222 persons with SCI. Eighty-six individuals with
      total cholesterol >200 mg/dL were referred for dietary consultation (group 1).
      The remainder with values <200 mg/dL and no consultation served as controls
      (group 2). RESULTS: At average follow-up of 16 months, group 1 demonstrated
      significant declines in total cholesterol and low-density lipoprotein cholesterol
      (LDL-C), whereas group 2 demonstrated significant increases in total cholesterol.
      Triglyceride levels followed similar but nonsignificant patterns. There were no
      significant changes in high-density lipoprotein cholesterol for either group. In
      group 1, 17% had clinically significant reductions in total cholesterol to <200
      mg/dL and 21% had reductions of LDL-C from >135 mg/dL to <135 mg/dL. CONCLUSIONS:
      Dietary intervention should be an initial treatment for those with SCI and
      moderately elevated total cholesterol, with the expectation that approximately
      20% will respond favorably.

PMID- 11587432
TI  - Predictors of loud snoring in persons with spinal cord injury.
AB  - BACKGROUND: Predictors of loud snoring were examined in a cohort of 197 persons
      with chronic spinal cord injury (SCI) recruited by advertisement and from a
      Veterans Affairs Medical Center SCI Service. METHODS: Data were collected on age,
      marital status, antispasticity medications, duration of injury, level and
      completeness of injury, stature, and weight. Body mass index (BMI) was calculated
      for all participants. A health questionnaire was used to collect data on snoring
      and respiratory history. Habitual snorers were defined as those who reported loud
      snoring more than 1 night per week. RESULTS: The mean age (+/- SD) was 51.2 +/-
      14.8 years, and 84 of 197 (42.6%) were habitual snorers. The most obese research
      subjects, regardless of antispasticity medication use, were more likely to report
      snoring, but the risk of snoring was greatest among subjects who were obese and
      used antispasticity medication. Subjects who used antispasticity medication and
      had a BMI above the median (> or = 25.3 kg/m2) had a 7-fold risk of reporting
      snoring compared with subjects below the median who did not use antispasticity
      medication (P = .001). The greatest risk occurred in those who used diazepam
      alone or baclofen and diazepam together and had a BMI at or above the median.
      Subjects who used these medications and had a BMI below the median did not have a
      significantly increased risk. Neurological motor completeness, level of injury,
      age, and years since injury were not significant predictors of snoring.
      CONCLUSION: Because snoring is a marker for obstructive sleep apnea (OSA), the
      data suggest that in obese individuals with SCI, the use of antispasticity
      medications may be a risk factor for OSA.

PMID- 11587434
TI  - Characterization of ultrastructural and metabolic abnormalities in semen from men
      with spinal cord injury.
AB  - BACKGROUND: In men with spinal cord injury (SCI), fertility is impaired because
      of a combination of ejaculatory dysfunction and poor semen quality. We
      hypothesized that ultrastructural and metabolic abnormalities of sperm could be
      an underlying factor in infertility in these men. METHODS: To investigate
      mechanisms contributing to the abnormal sperm parameters, we analyzed seminal
      constituents and sperm ultrastructure in ejaculates from 7 men with SCI and
      compared them with 5 control subjects. Sperm adenosine triphosphate (ATP) content
      was measured using a firefly luciferase bioluminescent assay kit, and
      ultrastructure was evaluated by electron microscopy. Seminal oxidative stress (8
      iso-prostaglandin F-2alpha [8-iso-PGF2alpha]) and transforming growth factor
      beta1 (TGF-beta1) levels were measured by specific enzyme-linked immunoabsorbent
      assay kits. RESULTS: Semen samples from men with SCI showed azoospermia (3) and
      severe asthenospermia (2; motility 0-5%). A majority (65%) of sperm from
      asthenospermic samples showed degenerative changes and significant axonemal
      defects. Incubation of normal sperm with SCI seminal plasma induced a
      concentration-dependent decrease in sperm motility (43%) accompanied by a
      significant drop in intracellular ATP content (33%). Semen samples from men with
      SCI exhibited levels of 8-iso-PGF2alpha 3.5-fold higher than those from controls
      and levels of TGF-beta1 that were 10% higher than those from controls.
      CONCLUSION: Our results suggest that seminal constituents of men with SCI are
      detrimental to sperm movement and that ultrastructural degenerative changes may
      contribute to the impaired sperm motility and viability seen in these patients.
      These preliminary results must be confirmed in larger patient populations and
      longitudinal studies.

PMID- 11587433
TI  - Efficacy and safety of oral sildenafil in men with erectile dysfunction and
      spinal cord injury.
AB  - OBJECTIVE: To assess the efficacy of sildenafil in men with spinal cord injury
      (SCI) and erectile dysfunction (ED). METHODS: Seventeen men with SCI were
      selected from February to September 1998 for sildenafil treatment of ED. The
      initial dose of 25 mg was increased by 25-mg increments as needed. Patients
      underwent baseline physical examination and answered questions from the abridged
      International Index of Erectile Function before and during therapy. RESULTS:
      Sixteen patients tolerated therapy; 1 developed hypotension and discontinued
      therapy. There was significant improvement in erectile function (P < .05) after
      5.3 +/- 2.2 months when compared with baseline or previous therapies (P < .05).
      Of the 17 patients, 94% recommended sildenafil to others. Six of these 16
      patients were available for long-term follow-up. There was further significant
      improvement in quality of erection (P < .05), but no change in satisfaction.
      CONCLUSION: Sildenafil is effective and well tolerated in men with SCI and ED.

PMID- 11587435
TI  - Predictors of pain 1 year post-spinal cord injury.
AB  - OBJECTIVE: To determine the predictive validity of demographic and medical
      characteristics to the subsequent development of pain 1 year post-spinal cord
      injury (SCI). DESIGN: Prospective longitudinal design using data from 18 Model
      Spinal Cord Injury Systems of Care. PARTICIPANTS: Adults 18 years or older with
      traumatic-onset SCI (n = 540) evaluated at 1 year postinjury. OUTCOME MEASURES: A
      single item from the Short Form-12 that assessed pain interference in day-to-day
      activities using a 5-point Likert scale. PREDICTOR VARIABLES: Demographic and
      medical characteristics, individual and total medical complications during
      rehabilitation, and insurance provider. RESULTS: Univariate analyses showed age,
      education, marital status, primary occupation at the time of injury, American
      Spinal Injury Association motor score, and sponsor of care to be related to pain
      interference 1 year post-SCI. Polychotomous logistic regression indicated that
      age and occupational status at the time of injury were the only significant
      unique predictors of pain interference. The youngest (aged 18-29 years) and
      oldest (aged 60 years and older) age groups reported the least amount of pain
      interference, whereas individuals unemployed at the time of injury were
      significantly more likely to report pain interference. None of the other
      predictor variables was significant. CONCLUSION: Age and occupational status
      appear to be important predictors of pain interference 1 year post-SCI. Future
      directions of study and limitations are discussed.

PMID- 11587436
TI  - The use of complementary and alternative therapies for chronic pain following
      spinal cord injury: a pilot survey.
AB  - OBJECTIVE: The purpose of this study was to determine the patterns and reasons
      for the use of complementary and alternative medicine (CAM) as a treatment for
      chronic pain among individuals with spinal cord injuries (SCI). METHODS:
      Telephone surveys were conducted in a sample of 77 people with SCI and chronic
      pain. RESULTS: Of those surveyed, 40.3% had used at least one CAM technique to
      manage chronic pain. The most common reason was dissatisfaction with conventional
      medicine. Acupuncture was the most frequently used modality, followed by massage,
      chiropractic manipulation, and herbal medicine. Acupuncture was rated lowest for
      satisfaction with pain relief, and massage was rated highest. Individuals not
      using conventional pain medication or who desired greater control over their
      health care practices tended to use more CAM techniques than others. Income,
      insurance coverage, and duration of pain were related to use of CAM. In general,
      CAM methods were effective for some and totally ineffective for others,
      indicating selective utility in this population. CONCLUSIONS: Despite this small
      opportunistic sample, the prevalence of CAM among individuals with SCI appears
      similar to that in the general population. A placebo-controlled trial is needed
      to evaluate the efficacy of various therapies in the SCI population. The fact
      that the most effective therapy, massage, was not frequently used suggests the
      need for more awareness of and research into this technique.

PMID- 11587437
TI  - 16S rDNA-based characterization of BTX-catabolizing microbial associations
      isolated from a South African sandy soil.
AB  - In the presence of different selection pressures, particularly pH and electron
      donor concentration, indigenous microbial associations which catabolize selected
      petroleum hydrocarbon components (benzene, toluene and o-, m- and p-xylene (BTX))
      were enriched and isolated from a petroleum hydrocarbon-contaminated KwaZulu
      Natal sandy soil. Electron microscopy revealed that, numerically, rods
      constituted the majority of the populations responsible for BTX catabolism.
      Molecular techniques (polymerase chain reaction (PCR) and 16S rDNA fingerprinting
      by denaturing-gradient gel electrophoresis (DGGE)) were employed to explore the
      diversities and analyze the structures of the isolated microbial associations.
      Pearson product-moment correlation indicated that the different, but chemically
      similar, petroleum hydrocarbon molecules, effected the isolation of different
      associations. However, some similar numerically-dominant bands characterized the
      associations. A 30% similarity was evident between the m- and o-xylene
      catabolizing associations regardless of the molecule concentration and the
      enrichment pH. PCR-DGGE was also used to complement conventional culture-based
      microbiological procedures for environmental parameter optimization. Band pattern
      differences indicated profile variations of the isolated associations which
      possibly accounted for the growth rate changes recorded in response to pH and
      temperature perturbations.

PMID- 11587438
TI  - Acetate conversion in anaerobic biogas reactors: traditional and molecular tools
      for studying this important group of anaerobic microorganisms.
AB  - Different methods were applied to study the role of aceticlastic methanogens in
      biogas reactors treating solid waste and wastewater. We used traditional
      microbiological methods, immunological and 16S rRNA ribosomal probes for
      detection of the methanogens. Using this approach we identified the methanogenic
      spp. and their activity. In biofilm systems, such as the UASB reactors the
      presence of the two aceticlastic methanogens could be correlated to the
      difference in the kinetic properties of the two species. In biogas reactors
      treating solid wastes, such as manure or mixture of manure and organic industrial
      waste, only Methanosarcina spp. were identified. Methanosarcina spp. isolated
      from different plants had different kinetics depending on their origin. Relating
      the reactor performance data to measurement of the activity by conventional
      microbiological methods gave a good indication of the microbial status of
      specific trophic groups. 16S rRNA probing confirmed these observations and gave a
      more detailed picture of the microbial groups present.

PMID- 11587439
TI  - Viscosity properties of mineral paraffinic base oils as a key factor in their
      primary biodegradability.
AB  - The primary biodegradability of two types of paraffinic base oils (solvent and
      catalytically dewaxed oils) and their blends was evaluated using the CEC L-33-A
      93 test. The biodegradability values varied between 10% and 75%. Base oil
      mixtures displayed varying contents in aromatic and polar compounds and a wide
      range of kinematic viscosity (KV) values, from roughly 10 to 600 cSt (at 40
      degrees C), while their viscosity indices were almost constant (90-100). The
      biodegradability of oils was closely related to their content in polycyclic
      aromatic hydrocarbons and was also decreasing with kinematic viscosity. For the
      two types of base oils, a linear relationship could be set between the
      biodegradation percentages and the logarithms of KV values. These results show
      that, beside overall chemical features such as the contents in aromatic
      compounds, KV may be a prominent parameter for assessing the primary
      biodegradability of mineral base oils.

PMID- 11587440
TI  - Growth rate influences reductive biodegradation of the organophosphorus pesticide
      demeton by Corynebacterium glutamicum.
AB  - The organophosphorous pesticide, demeton-S-methyl was transformed by
      Corynebacterium glutamicum in co-metabolism with more readily degradable
      substrates. Glucose, acetate and fructose were tested as growth substrates, and
      the highest demeton-S-methyl biotransformation average rate (0.78 mg l(-1) h(-1))
      and maximum instantaneous rate (1.4 mg l(-1) h(-1)) were achieved on fructose.
      This higher efficiency seems to be linked to the atypical behavior of C.
      glutamicum grown on fructose, characterized by a prolonged period of accelerating
      growth instead of a constant growth rate observed on glucose or acetate. More
      precisely, for growth rates in the 0.1-0.4 h(-1) range, a direct coupling between
      the specific demeton-S-methyl consumption rate and the growth rate was
      demonstrated on fructose during batch-, steady state continuous- or continuous
      cultures with a controlled transient growth rate (accelerostat technology). The
      demeton-S-methyl biotransformation was more favoured during an acceleration phase
      of the growth rate.

PMID- 11587441
TI  - Degradation of organic contaminants found in organic waste.
AB  - In recent years, great interest has arisen in recycling of the waste created by
      modern society. A common way of recycling the organic fraction is amendment on
      farmland. However, these wastes may contain possible hazardous components in
      small amounts, which may prevent their use in farming. The objective of our study
      has been to develop biological methods by which selected organic xenobiotic
      compounds can be biotransformed by anaerobic or aerobic treatment. Screening
      tests assessed the capability of various inocula to degrade two phthalates di-n
      butylphthalate, and di(2-ethylhexyl)phthalate, five polycyclic aromatic
      hydrocarbons, linear alkylbenzene sulfonates and three nonylphenol ethoxylates
      under aerobic and anaerobic conditions. Under aerobic conditions, by selecting
      the appropriate inoculum most of the selected xenobiotics could be degraded.
      Aerobic degradation of di(2-ethylhexyl)phthalate was only possible with leachate
      from a landfill as inoculum. Anaerobic degradation of some of the compounds was
      also detected. Leachate showed capability of degrading phthalates, and anaerobic
      sludge showed potential for degrading, polycyclic aromatic hydrocarbons, linear
      alkylbenzene sulfonates and nonyl phenol ethoxylates. The results are promising
      as they indicate that a great potential for biological degradation is present,
      though the inoculum containing the microorganisms capable of transforming the
      recalcitrant xenobiotics has to be chosen carefully.

PMID- 11587442
TI  - Bioremediation of oil polluted aquatic systems and soils with novel preparation
      'Rhoder'.
AB  - This paper summarises the experience accumulated during the field application of
      biopreparation 'Rhoder' (solely or in a combination with preliminary mechanical
      collection of free oil) for remediation of oil polluted aquatic systems and soils
      in the Moscow region and Western Siberia during 1994-1999. It was demonstrated
      that 'Rhoder' had a very high efficiency (>99%) for bioremediation of the open
      aquatic surfaces (100 m2 bay of the River Chernaya, two 5,000 m2 lakes in
      Vyngayakha) at initial level of oil pollution of 0.4-19.1 g/l. During remediation
      of the wetland (2,000 m2) in Urai (initial level of oil pollution of 10.5 g/l), a
      preliminary mechanical collection of oil was applied (75% removal) followed by a
      triple treatment with 'Rhoder'. It resulted in an overall treatment efficiency of
      94%. Relatively inferior results of bioremediation of the 10,000 m2 wetland in
      Vyngayakha (65% removal) and the 1,000 m2 marshy peat soil in Nizhnevartovsk (19%
      removal) can be attributed to the very high initial level of oil pollution (24.3
      g/l and >750 g/g dry matter, respectively) aggravated by the fact that it was
      impossible to apply a preliminary mechanical collection of oil on these sites. A
      possible strategy for remediation of such heavily polluted sites is discussed.

PMID- 11587443
TI  - Nutrient-limited biodegradation of PAH in various soil strata at a creosote
      contaminated site.
AB  - The effects of nutrient addition on the in situ biodegradation of polycyclic
      aromatic hydrocarbons in creosote contaminated soil were studied in soil columns
      taken from various soil strata at a wood preserving plant in Norway. Three
      samples were used: one from the topsoil (0-0.5 m), one from an organic rich layer
      (2-2.5 m) and one from the sandy aquifer (4.5-5 m). The addition of inorganic
      nitrogen and phosphorous stimulated the degradation of polycyclic aromatic
      hydrocarbons (PAHs) in the top soil and the aquifer sand. These two soils, which
      differed strongly in contamination levels, responded similarly to nutrient
      addition with the corresponding degradation of 4-ring PAHs. The ratio between
      available nitrogen (N) and phosphorous (P) might explain the degree of
      degradation observed for the 4-ring PAHs. However, the degree of degradation of 3
      ring PAHs did not significantly increase after nutrient addition. An increase in
      the respiration rate, after nutrient addition, could only be observed in the
      topsoil. In the aquifer sand, 4-ring PAH degradation was not accompanied by an
      increase in the respiration rate or the number of heterotrophic micro-organisms.
      PAH degradation in the organic layer did not respond to nutrient addition. This
      was probably due to the low availability of the contaminants for micro-organisms,
      as a result of sorption to the soil organic matter. Our data illustrate the need
      for a better understanding of the role of nutrients in the degradation of high
      molecular weight hydrocarbons for the successful application of bioremediation at
      PAH contaminated sites.

PMID- 11587444
TI  - Anaerobic treatability and biogas production potential studies of different agro
      industrial wastewaters in Turkey.
AB  - The anaerobic treatability and methane generation potential of the wastewaters of
      the three important agro-industries in Turkey, namely, cheese-making, poultry
      breeding and the olive-oil mill industries were studied. Biochemical methane
      potential (BMP) experiments were conducted for different initial chemical oxygen
      demand (COD) concentrations. The results indicate that anaerobic treatment was
      possible for all the wastewaters studied and the biogas produced had a high
      methane content.

PMID- 11587445
TI  - Acidogenic fermentation of source separated mixtures of vegetables and fruits
      wasted from supermarkets.
AB  - A pilot scale mesophilic anaerobic acidogenic fermenter was fed with mixtures of
      vegetables and fruits shredded by a hammer mill and mixed in a stock tank, in
      order to produce a liquid phase suitable as RBCOD source in denitrification and
      EBPR processes. Different operative conditions were studied working with a HRT in
      the range 1-12 days. The effluent coming from the fermenter was screw pressed,
      and the solid phase was recycled adopting different ratios to the fermenter, in
      order to define its effect on the final liquid phase composition. The variations
      of the VFA, lactate, methyl and ethyl alcohol concentrations, TCOD, SCOD and pH
      during more than one year were analysed and discussed both with reference to the
      fresh feed, and to the content of the fermenter. It was found that almost all the
      organic matter in the liquid phase inside the fermenter was represented by VFA
      (mainly acetate), lactate (in particular) and methyl and ethyl alcohols when HRT
      was longer than 6 days.

PMID- 11587446
TI  - Anaerobic waste digestion in Germany--status and recent developments.
AB  - Anaerobic treatment processes are especially suited for the utilization of wet
      organic wastes from agriculture and industry as well as for the organic part of
      source-separated household wastes. Anaerobic degradation is a very cost-effective
      method for treating biogenic wastes because the formed biogas can be used for
      heat and electricity production and the digester residues can be recycled to
      agriculture as a secondary fertilizer. Anaerobic technology will also be used for
      the common treatment of wastes together with renewable energy crops in order to
      reduce the CO2-emissions according the Kyoto protocol. Various process types are
      applied in Germany which differ in material, reaction conditions and in the form
      of the used reactor systems. The widespread introduction of anaerobic digestion
      in Germany has shown that biogenic organic wastes are a valuable source for
      energy and nutrients. Anaerobic waste treatment is done today in approx. 850
      biogas plants on small farm scale as well as on large industrial scale with the
      best beneficial and economic outcome. Due to some new environmental protection
      acts which promote the recycling of wastes and their utilization for renewable
      energy formation it can be expected that several hundreds new biogas plants will
      be built per year in Germany. In order to use the synergetic effects of a
      combined fermentation of wastes and energy crops new process types must be
      developed in order to optimize the substrate combinations and the process
      conditions for maximum biodegradation.

PMID- 11587447
TI  - Application of biofiltration to the degradation of hydrogen sulfide in gas
      effluents.
AB  - A laboratory scale bioreactor has been designed and set up in order to degrade
      hydrogen sulfide from an air stream. The reactor is a vertical column of 7 litre
      capacity and 1 meter in height. It is divided into three modules and each module
      is filled with pellets of agricultural residues as packing bed material. The gas
      stream fed into the reactor through the upper inlet consists of a mixture of
      hydrogen sulfide and humidified air. The hydrogen sulfide content in the inlet
      gas stream was increased in stages until the degradation efficiency was below
      90%. The parameters to be controlled in order to reach continuous and stable
      operation were temperature, moisture content and the percentage of the compound
      to be degraded at the inlet and outlet gas streams (removal or elimination
      efficiency). When the H2S mass loading rate was between 10 and 40 g m(-3) h(-1),
      the removal efficiency was greater than 90%. The support material had a good
      physical performance throughout operation time, which is evidence that this
      material is suitable for biofiltration purposes.

PMID- 11587448
TI  - Performance of a thermophilic sulfate and sulfite reducing high rate anaerobic
      reactor fed with methanol.
AB  - Thermophilic sulfate and sulfite reduction was studied in lab-scale Expanded
      Granular Sludge Bed (EGSB) reactors operated at 65 degrees C and pH 7.5 with
      methanol as the sole carbon and energy source for the sulfate- and sulfite
      reducing bacteria. At a hydraulic retention time (HRT) of 10 h, maximum sulfite
      and sulfate elimination rates of 5.5 g SO3(2-) L(-1) day(-1) (100% elimination)
      and 5.7 g SO4(2-) L(-1) day(-1) (55% elimination) were achieved, resulting in an
      effluent sulfide concentration of approximately 1800 mg S L(-1). Sulfate
      elimination was limited by the sulfide concentration, as stripping of H2S from
      the reactor with nitrogen gas was found to increase the sulfate elimination rate
      to 9.9 g SO4(2-) L(-1) day(-1) (100% elimination). At a HRT of 3 h, maximum
      achievable sulfite and sulfate elimination rates were even 18 g SO3(2-) L(-1)
      day(-1) (100% elimination) and 11 g SO4(2-) L(-1) day(-1) (50% elimination). At a
      HRT of 3 h, the elimination rate was limited by the biomass retention of the
      system. 5.5 +/- 1.8% of the consumed methanol was converted to acetate, which was
      not further degraded by sulfate reducing bacteria present in the sludge. The
      acetotrophic activity of the sludge could not be stimulated by cultivating the
      sludge for 30 days under methanol-limiting conditions. Omitting cobalt as trace
      element from the influent resulted in a lower acetate production rate, but it
      also led to a lower sulfate reduction rate. Sulfate degradation in the reactor
      could be described by zeroth order kinetics down to a threshold concentration of
      0.05 g L(-1), while methanol degradation followed Michaelis-Menten kinetics with
      a Km of 0.037 g COD L(-1).

PMID- 11587449
TI  - In situ corrosion control in industrial water systems.
AB  - The main objective of this study was to evaluate the efficacy of a biocide and a
      corrosion inhibitor against the corrosion of a circulating pipe in a cooling
      tower. Isothiazolone was tested as the industrial biocide. The results showed
      that the biocide by itself or combined with a dispersant was not efficient to
      control corrosion in the industrial system. Corrosion rates of 0.324 mm/year were
      recorded in both the presence and absence of the biocide. Corrosion control was
      successfully accomplished by using a corrosion inhibitor. In the latter case the
      maximum corrosion rate of 0.024 mm/year were obtained.

PMID- 11587450
TI  - The assessment of the vulnerable atherosclerotic plaque using MR imaging: a brief
      review.
AB  - The study of atherosclerotic disease during its natural history and after
      therapeutic intervention may enhance our understanding of the progression and
      regression of this disease and will aid in selecting the appropriate medical
      treatments or surgical interventions. Several invasive and non-invasive imaging
      techniques are available to assess atherosclerotic disease vessels. Most of these
      techniques are strong in identifying the morphological features of the disease
      such as lumenal diameter and stenosis or wall thickness, and in some cases
      provide an assessment of the relative risk associated with the atherosclerotic
      disease. However, none of these techniques can fully characterize the composition
      of the atherosclerotic plaque in the vessel wall and therefore are incapable of
      identifying the vulnerable plaques. High-resolution, multi-contrast, magnetic
      resonance (MR) can non-invasively image vulnerable plaques and characterize
      plaques in terms of lipid and fibrous content and identify the presence of
      thrombus or calcium. Application of MR imaging opens up whole new areas for
      diagnosis, prevention, and treatment of atherosclerosis.

PMID- 11587451
TI  - Possibilities of transesophageal MRI for assessment of aortic disease: a review.
AB  - The thoracic aortic wall is a common site of atherosclerotic plaque in humans.
      Tools for serial, non-invasive assessment of these plaques are of value for
      addressing gaps in our basic understanding of the biology of plaque rupture and
      its relationship to atherosclerotic disease progression as well as for monitoring
      response to anti-atherosclerotic interventions in therapeutic clinical trials.
      Common approaches to assessment of the wall of the thoracic aorta in vivo are
      limited. Here we discuss some of the challenges and limitations encountered by
      conventional techniques and review a novel approach, transesophageal MRI (TEMRI).
      Initial experiences in applying the TEMRI approach to assessment of aortic
      morphology and pathology are discussed.

PMID- 11587452
TI  - NMR sequences for biochemical analysis and imaging of vascular diseases.

PMID- 11587453
TI  - Cardiac gated breath-hold black blood MRI of the coronary artery wall: an in vivo
      and ex vivo comparison.
AB  - BACKGROUND: High resolution magnetic resonance (MR) imaging of the coronary
      artery wall in vivo has been limited by the cardiac and respiratory motion, flow
      artifacts as well as the relatively small size of the coronary arteries. We
      sought to validate in vivo black blood MR imaging of the coronary artery wall
      using a double inversion recovery fast spin echo MR imaging sequence with limited
      breath-holding and cardiac gating for suppression of motion artifacts by
      comparison with ex vivo MR imaging. METHODS: Yorkshire albino swine (n = 6) were
      used in this study and coronary lesions were induced with balloon angioplasty.
      Four weeks after balloon injury of the coronary arteries MR imaging of the
      coronary artery lesions was performed. High resolution in vivo and ex vivo images
      of the coronary artery wall and lesions were obtained using a double inversion
      recovery fast spin echo sequence in a 1.5 T MR system. There was a statistically
      significant agreement (p < 0.0001) between measurements of vessel wall area (r =
      0.87, slope = 0.87) and maximal wall thickness (r = 0.84, slope = 0.88) from in
      vivo and ex vivo MR images of the coronary arteries. The mean differences between
      in vivo and ex vivo measurements were 0.56 +/- 1.98 mm2 for vessel wall area and
      0.02 +/- 0.36 mm for maximal wall thickness. CONCLUSIONS: Using breathholding and
      cardiac gating, it is possible to perform high resolution MR imaging of the
      coronary artery wall in vivo with good suppression of motion artifacts with a
      double inversion recovery fast spin echo black blood imaging sequence.

PMID- 11587454
TI  - Methods for quantification of coronary artery calcifications with electron beam
      and conventional CT and pushing the spiral CT envelope: new cardiac applications.
AB  - Detection of coronary artery calcifications with slice by slice prospective ECG
      triggering is feasible with electron beam CT as well as with single and multi-row
      detector CT (MDCT). The radiation exposure to the patient to obtain comparable
      image quality is similar for all three modalities utilizing this prospective
      acquisition technique. Alternatively, coronary screening can be performed by MDCT
      with retrospective EKG spiral gating. Radiation exposure to the patient with this
      technique is significantly higher than with prospective triggering. Nevertheless,
      acquisition of the entire volume of the heart with retrospective gating holds
      promise to improve reproducibility of coronary calcium measurements, especially
      in patients with a low amount of coronary calcium and in patients with atrial
      fibrillation. If retrospective gating is used for CT angiography (CTA) with MDCT
      this allows to use thin slices (1.25 mm) and to perform the acquisition within
      one breath hold period (app. 35 s). This technique is currently limited by the
      temporal resolution per slice (250 ms). In order to achieve diagnostic image
      quality the heart rate of the patient thus needs to be sufficiently low.
      Therefore, in cases with heart rates significantly higher than 70 beats/min
      betablocker have to be administered for patient preparation as long as there are
      no contraindications for such a regimen. Because of low image noise and high
      spatial resolution CTA with MDCT is able to display the entire extent of
      atherosclerosis allowing to visualize calcified as well as non-calcified plaques
      of the coronary arteries. Under clinical conditions CTA has the potential to
      accurately rule out or diagnose significant coronary stenoses of the proximal and
      mid-segments of the coronary artery tree when compared to conventional selective
      coronary angiography.

PMID- 11587455
TI  - Coronary artery calcium quantification with retrospectively gated helical CT:
      protocols and techniques.
AB  - Current generation Helical Computed Tomography, when coupled with cardiac gating
      can be used to measure coronary vascular calcium. In this article we review the
      development of retrospectively gated helical computed tomography on a single
      slice HCT system and its relation to electron beam CT. The impact of heart rate
      on selection of helical pitch for the creation of a diastolic image set is
      detailed, as well as, scanning and post-processing techniques are discussed. The
      development and initial experience of cardiac gating with multidetector CT
      systems is presented.

PMID- 11587456
TI  - The importance of the maximum pulmonary artery regurgitant velocity following
      repair of tetralogy of Fallot: a pilot study.
AB  - BACKGROUND: Tetralogy of Fallot repairs invariably result in pulmonary
      regurgitation with the long term sequelae of ventricular dilatation and
      dysfunction. OBJECTIVE: The purpose of this study is to correlate pulmonary flow
      parameters with right ventricular size and function. MATERIALS AND METHODS:
      Pulmonary artery velocity was mapped by magnetic resonance flow analysis in seven
      children with pulmonary regurgitation following tetralogy of Fallot repair. Right
      and left ventricular volumes were determined by Simpson's rule from double
      oblique cine gradient echo images of the heart. The ejection fraction was
      calculated for each ventricle. Right ventricular enlargement was normalized for
      patient size by calculating the ratios of right ventricle end diastolic and end
      systolic volumes to the left ventricle end diastolic and end systolic volumes
      respectively (EDV RV:LV and ESV RV:LV). The maximum pulmonary artery antegrade
      and retrograde velocities and the ratio of the time for antegrade to regurgitant
      flow were compared to ventricular function and volume measurements by regression
      analysis. RESULTS: A significant linear relationship between the maximum
      regurgitant pulmonary artery velocity and EDV RV:LV was identified (r2 = 0.82).
      CONCLUSION: An elevated maximum pulmonary regurgitant velocity correlated well
      with the degree of right ventricular enlargement in patients following tetralogy
      of Fallot repair. If the results are verified by a larger study, the maximum
      pulmonary regurgitant velocity may be substituted for the more cumbersome direct
      measurement of right ventricular size.

PMID- 11587457
TI  - Real-time three-dimensional echocardiography: an overview.
AB  - Conventional echocardiography and its representation of the heart in a two
      dimensional format only provide partial information about cardiac function. Real
      time three-dimensional echocardiography is a recently developed technique based
      on the design of an ultrasound transducer with a matrix array that
      instantaneously acquires the image contained in a pyramidal volume. The
      simultaneous display of multiple tomographic images allows the anatomically
      correct examination of any structure contained within the volumetric image.
      Software and technologies based on high performance computers designed for
      graphic handling of three-dimensional images permit the rapid mapping of the
      volumetric image and provide possibilities beyond those of the echograph. Using
      this methodology, it is possible to simultaneously visualize multiple
      superimposed planes in an interactive manner. Real-time three-dimensional
      echocardiography also allows a quantitative assessment of cardiac volumes,
      ventricular mass, and myocardium with contraction and/or perfusion abnormalities.
      This technique thus expands the abilities of non-invasive cardiology and may open
      new doors for the evaluation of cardiac disease.

PMID- 11587458
TI  - In vitro determination of cardiac ventricular volumes using MRI at 1.0 T in a
      porcine heart model.
AB  - PURPOSE: To determine the accuracy of a 1.0 T MR system with a standard gradient
      system for quantification of left and right ventricular volumes. A porcine heart
      model in vitro was used. METHODS: In eight explanted porcine hearts the atria
      were removed and the aorta and the pulmonary truncus were cannulated. Defined
      volumes were injected into the ventricles. Magnetic resonance imaging (MRI): FFE
      EPI (Multishot EPI) was used. Papillary muscles and trabeculae were excluded.
      True volumes and MR measurements were analysed separately for both ventricles and
      by both investigators. RESULTS: The correlation of the true volumes and MR
      measurements was >0.99. MRI was found to be investigator independent in assessing
      right and left ventricular volumes in vitro. CONCLUSIONS: MRI at 1.0 T using
      standard equipment can be used to quantitate cardiac ventricular volumes in vitro
      with high accuracy.

PMID- 11587459
TI  - The Declaration of Helsinki and emergency medicine research.

PMID- 11587460
TI  - Measurement of skills in cardiopulmonary resuscitation--do professionals follow
      given guidelines?
AB  - Since it is suggested that only effective cardiopulmonary resuscitation (CPR)
      improves survival rates, quality control of training outcomes is important and
      comparisons between different training methods are desirable. The aim of this
      study was to test a model of quality assurance, consisting of a computer program
      combined with the Brennan et al. checklist, for evaluation of CPR performance. A
      small group of trained medical professionals (cardiac care unit nurses) (n = 10)
      was used in this pilot study. The result points out several points of concern:
      half of the participants did not open the airway prior to breathing control. Over
      90% of all inflations were 'too fast' and 71% were 'too much'. Only 6.5% of the
      inflations were correct. On average, the participants made 5.4 inflations per
      minute. Concerning chest compressions, 40% were 'too deep' while only 4% were
      'too shallow'. In spite of the fact that the participants had an average rate at
      95 compressions per minute the number of compressions varied between 32 and 51
      during 1 minute. When new guidelines are discussed, it would be beneficial if
      they were tested by a number of people to investigate if following the guidelines
      is at all possible.

PMID- 11587461
TI  - Creatinine-kinase-MB determination in non-cardiac trauma: its difference with
      cardiac infarction and its restricted use in trauma situations.
AB  - Cardiac injuries can be life threatening. The possibility of late complications
      urges the practitioner to search for any evidence of cardiac trauma. But the
      diagnosis of cardiac injury remains difficult. Electrocardiography and cardiac
      enzyme determination are most widely used, because they are readily available.
      Many studies advocate creatine-kinase-MB (CK-MB) isoenzyme levels as a sensitive
      test for cardiac contusion. Others have discarded CK-MB testing as useless in
      trauma situations. An elevated CK-MB value in haemodynamically stable patients
      may confuse the individual practitioner. To better clarify its role we
      investigated the course of CK/CK-MB release after trauma, with no or only a very
      small chance of cardiac injury and compared it with patients with severe chest
      trauma having cardiac complications. A total of 25 trauma patients with only
      skeletal muscle injury were studied. Blood samples were taken during the first 4
      days after trauma. These results were compared with those of a group of 91
      consecutive patients with severe chest injury, including 10 with cardiac
      complications. Initial results in skeletal trauma patients were indicative of
      cardiac injury (CK > 5% of total CK and at least 20 U/l) in 10 patients. These
      findings were identical to those found in patients with severe chest injury
      having cardiac complications. CK/CK-MB tests are frequently positive after trauma
      without cardiac injury, even when selective criteria are used. The time each
      isoenzyme is released from muscle tissue after trauma greatly influences the
      outcome of the test. As this release does not occur at the same moment for each
      isoenzyme, the test result is very much time-dependent. As a result of these
      findings CK-MB testing tends to cause more confusion than clarification in trauma
      situations. We therefore eliminated CK-MB testing from our trauma protocol as a
      screening investigation for cardiac injury.

PMID- 11587462
TI  - Adherence to antibiotics prescribed in an accident and emergency department: the
      influence of consultation factors.
AB  - The objective of this study was to investigate the extent of non-adherence to
      prescribed antibiotics and the relationship of non-adherence to consultation and
      attitudinal factors. Self-completion postal questionnaires were sent to 202
      consecutive adult attenders to an accident and emergency (A&E) department who had
      been given antibiotics to take home, within a week of the A&E attendance. The
      questionnaire included a detailed log of dosing, two sections of eight questions
      each on the patients' perceptions of the consultation and of their attitudes to
      medicines in general, which were marked on Likert scales; and questions inviting
      free text answers. Efforts were made to maximize the response rate, and to
      contact a random sample of 10 non-responders to assess any non-response bias. The
      response rate was 56%. The non-responders sampled reported similar non-adherence
      to that of the responders. Of the 113 responders, 10 (9%) indicated that they had
      taken none of their prescribed medicines, and 25 (22%) that they had taken less
      than 80%. The most common pattern of non-adherence was early cessation. Two
      aspects of the consultation (expectations about a prescription, and that there
      were too many tablets) were related to adherence. In conclusion, this study
      suggests that the effectiveness of some A&E consultations is reduced by
      inadequate exploration of patients' concerns and expectations.

PMID- 11587464
TI  - Developing an enhanced minor injury unit for support of urban festivities.
AB  - The aim of this study was to plan a temporary minor injury unit (MIU) in an urban
      centre, to cope with large numbers of minor casualties from a predicted mass
      gathering. Numerous minor injuries could potentially overwhelm the local accident
      and emergency (A&E) department. To prevent this, a temporary MIU was planned in
      the city centre, developed by a multidisciplinary team of staff from the base A&E
      department and the more central hosting hospital, plus police and ambulance
      services. Issues involved included: identification of premises; training
      personnel; development of clinical protocols; determining equipment requirements;
      liaison with other departments; and public education. An electively closed ward
      was selected as a site. Two experienced doctors worked each shift, plus three
      local nursing staff directed by a senior A&E nurse. Joint training sessions were
      organized, promoting team cohesion. Clinical protocols, based on guidelines for a
      pre-existing MIU run by the A&E department, were augmented to recognize the
      increased capability available with the presence of medical staff. Equipment and
      drug requirements were dictated by these protocols. Planning was completed early
      to allow dissemination of information to the public. Despite this, the unit
      failed to have an impact on attendance to the main A&E department. Developing an
      MIU requires close coordination of numerous agencies and departments, plus
      adequate public education. Accurate predictions of casualties are needed to plan
      equipment and staffing levels, but can be difficult to determine.

PMID- 11587463
TI  - Snakebite poisoning in children--a call for unified clinical guidelines.
AB  - In Israel, there are no uniform guidelines for the treatment policy of children
      snake-bitten by the Vipera palaestinae, the most abundant venomous snake in the
      country. We conducted a retrospective study aiming to compare treatment policies
      in two different medical centers. We found significant differences regarding
      admission and steroid administration criteria. Although the differences between
      the centers regarding anti-venom administration did not reach statistical
      significance, there were substantial differences. Neither of the centers had a
      well-established policy for the treatment of snake envenomation in children. In
      the era of cost containment, a policy of routine admission of children to the
      PICU service following V. palaestinae envenomation is unjustified, especially
      since the introduction of a specific monovalent anti-venom into the therapeutic
      armamentarium.

PMID- 11587465
TI  - The effect of lidocaine/prilocaine cream on an experimental wound healing model.
AB  - The effects of lidocaine/prilocaine cream on wound healing were evaluated in this
      study. An incisional wound model on abdominal wall was performed on mice. A full
      thickness skin incision 2 cm in length was performed then it was sutured
      primarily with 4/0 polypropylene. In group I (n = 10) only suturing was done
      (control group), in group II (n = 10) lidocaine cream was applied after suturing
      on wound site and it was repeated for 6 days (twice in a day), in group III (n =
      10) lidocaine/prilocaine cream was applied topically after suturing and repeated
      6 days (twice in a day). At day 7, incisions were excised for evaluating tensile
      strength and 5-hydroxyproline (5-HP) values. Tensile strength values were lowest
      in control group and highest in lidocaine/prilocaine treatment group. 5-HP values
      were also expressed the same results. Both tensile strength and 5-HP values
      increased significantly in treatment groups in regard to the control (p < 0.05).
      It was concluded that lidocaine/prilocaine cream as topical anaesthetic agent had
      no adverse effect in an incisional wound model, furthermore it may have some
      beneficial effects on wound healing which remains to be evaluated and it can be
      used safely in day-to-day emergency practices.

PMID- 11587466
TI  - Reduction in gram-positive pneumonia and antibiotic consumption following the use
      of a SDD protocol including nasal and oral mupirocin.
AB  - The objective of this prospective, randomized, double-blind study was to evaluate
      the effect of the addition of mupirocin to the 'classical' topical SDD regimen
      (tobramycin 80 mg, polymyxin E 100 mg, amphotericin B 500 mg) on the development
      of ICU-acquired infections due to gram-positive bacteria. The study was carried
      out in an intensive care unit (ICU) of a 1400-bed community hospital. All
      patients admitted to the ICU during a 16-month period, who were expected to
      require mechanical ventilation for more than 24 hours, were randomized to receive
      either the 'classical' SDD regimen (Group A) or a modified regimen with mupirocin
      (Group B). Data from 223 patients requiring mechanical ventilation for at least
      48 hours, who were neither infected nor receiving antibiotics on ICU admission,
      was analysed. A 2% paste containing tobramycin, polymyxin E and amphotericin B
      was applied every 6 hours in the oropharynx to the patients in Group A, while in
      Group B this formula was modified with the addition of 2% mupirocin. In Group B
      0.2 ml of a 2% mupirocin ointment was also applied four times daily in both
      nostrils. Patients in Group A received a soft paraffin ointment as a placebo
      indistinguishable from mupirocin. Patients in both groups received the classic
      SDD regimen through the nasogastric tube. Systemic antibiotic prophylaxis was not
      used. Data on lower airway infection, and blood infection, infections of
      intravascular catheters, antibiotic consumption and expenditures for antibiotics
      were analysed. The diagnosis of ventilator-associated pneumonia (VAP) was based
      on quantitative cultures of protected specimen brush samples (PSB) or on the
      results of distal broncho-alveolar lavage (BAL). One hundred and four patients
      received the 'classical' SDD and 119 the modified regimen. Overall 29 patients,
      20 in Group A and nine in Group B (p < 0.02) had a total of 33 cases of
      pneumonia. There were 23 episodes of pneumonia in Group A and 10 in Group B (p <
      0.02). Gram-positive bacteria were isolated from samples in 17 episodes in Group
      A and six in Group B (p < 0.02). Staphylococcus aureus was isolated in nine cases
      of pneumonia in Group A and once in the 'mupirocin' group (p < 0.05). MRSA were
      isolated in seven out of nine cases in Group A and in the only case in Group B.
      There were no differences in the isolation of gram-negative bacilli. Antibiotic
      consumption and cost were lower in Group B. In conclusion, our data show that the
      topical use of a modified formula of SDD, with the addition of mupirocin to the
      oral paste and in the anterior nares, is associated with a reduction in lung
      infections caused by gram-positives and in a reduction in antibiotic consumption
      and in the overall expenditure for antibiotics.

PMID- 11587467
TI  - Risk prevention, avoidable deaths and mortality-morbidity reduction in head
      injury.

PMID- 11587468
TI  - Ethical principles for medical research involving human subjects.

PMID- 11587469
TI  - Life-threatening traumatic rupture of a liver hydatid cyst.

PMID- 11587470
TI  - Unusual cardiac injury following blunt chest trauma.
AB  - Cardiac injury following blunt chest trauma is known to occur, but traumatic
      rupture of ventricular septum is a rare injury, especially following blunt chest
      trauma. A case of a 20-year-old male is presented who fell on his back from a 9th
      floor window and was resuscitated for 3 hours to no avail. Post-mortem
      examination confirmed a fracture of the pelvis, pulmonary contusion and rupture
      of ventricular septum of the heart.

PMID- 11587471
TI  - Abrupt-onset oculomotor paralysis: an endocrine emergency.
AB  - Pituitary apoplexy is a severe and potentially life-threatening condition that
      may be highly variable in its clinical presentation. We report a 37-year-old man
      presenting to the emergency department with diplopia that abruptly developed
      while he was eating canned and bottled food prepared at home. A computed
      tomography scanning revealed an isodense mass within the sellar region and,
      subsequently, a magnetic resonance imaging showed a pituitary apoplexy causing a
      compression of the right III and VI oculomotor nerves. There was no improvement
      with hydrocortisone therapy and the patient underwent a transsphenoidal excision
      of the mass with an uneventful course. Pituitary apoplexy may raise in the
      appropriate setting the suspicion of botulism. The abrupt-onset paralysis of
      oculomotor nerves has been described as the chief presenting sign of pituitary
      apoplexy in only few cases including this. A pathophysiology, differential
      diagnosis with botulism and other causes of multiple cranial nerve paralysis, and
      treatment are described.

PMID- 11587472
TI  - Cardiac tamponade secondary to chest tube placement.
AB  - A 69-year-old woman was hospitalized because of a left-sided pneumothorax due to
      chronic obstructive pulmonary disease. During chest tube placement she developed
      hypotension and a decrease in peripheral oxygen saturation. A diagnosis of heart
      tamponade was made and the patient was treated successfully with
      pericardiocentesis and placement of a pericardial drain. Cardiac tamponade
      following chest tube placement is a rare and serious complication. When the
      clinical condition deteriorates following chest tube insertion, cardiac tamponade
      should be considered.

PMID- 11587473
TI  - Out-of-hospital thrombolytic therapy during cardiopulmonary resuscitation in
      refractory cardiac arrest due to acute myocardial infarction.
AB  - Out-of-hospital thrombolytic therapy was administrated to a 53-year-old woman
      with confirmed acute myocardial infarction and refractory cardiac arrest.
      Standard advanced cardiac life support measures were performed by an out-of
      hospital critical care team but they were unsuccessful. Thrombolytic therapy was
      given as a rescue therapy after prolonged cardiopulmonary resuscitation. The
      patient recovered a sinus rhythm and circulation 20 minutes after a bolus
      infusion of tissue plasminogen activator and was fit to be transported to the
      hospital. Reversal of arterial occlusion was confirmed at the hospital. There was
      no sequelae related to thrombolytic therapy and the patient was finally
      discharged 21 days later. This is the first published report of out-of-hospital
      thrombolytic therapy during cardiopulmonary resuscitation for a patient with
      refractory cardiac arrest due to acute myocardial infarction.

PMID- 11587474
TI  - Intoxication with 100 grams of mercury: a case report and importance of
      supportive therapy.
AB  - Nearly everyone is at risk of acute and chronic toxic exposure to hazardous
      substances in the ambient environment. Morbidity and mortality following an
      overdose are reduced by intensive appropriate supportive therapy. A well-trained
      medical team is required for the administration of intensive clinical care, which
      includes enough equipment for monitoring the patient's status. In this paper we
      present a student who, after attending a dentist faculty, ingested 100 grams of
      pure inorganic mercury in order to commit suicide and was treated with forced
      diuresis, whole bowel irrigation, and D-penicillamine. The latter was found
      following 48 hours of therapy and only used for 4 days because of lack of
      availability of other antidotes for mercury in our city.

PMID- 11587475
TI  - Optimizing drug development: strategies to assess drug metabolism/transporter
      interaction potential--toward a consensus.

PMID- 11587476
TI  - The measurement of small quantities of amorphous material--should we be
      considering the rigid amorphous fraction?

PMID- 11587477
TI  - Sequential processing of human ProIL-1beta by caspase-1 and subsequent folding
      determined by a combined in vitro and in silico approach.
AB  - PURPOSE: Interleukin-1beta is a multifunctional cytokine produced by activated
      monocytes and macrophages that requires caspase-1 (IL-1 converting enzyme/ICE) to
      process the 31kDa inactive precursor protein to the biologically active 17kDa
      peptide. This activation event involves ICE cleavage at Asp27 (site 1) and Asp116
      (site 2). To address the sequential processing at ICE cut sites we combined in
      vitro analysis and molecular modeling to investigate the sequence of molecular
      events. METHODS: Pulse chase labeling followed by immunoprecipitation of IL-1beta
      in activated human monocyte lysates demonstrated sequential cutting by ICE at
      site 1 before site 2 in vitro. To corroborate these findings, we constructed a
      homology model of proIL-1beta after the crystal structure of another ICE
      substrate, human alpha1-antitrypsin (23% sequence identity). RESULTS: Comparative
      modeling revealed that site 1 on proIL-1beta is accessible to ICE but site 2 is
      not. Molecular dynamics simulations following ICE cleavage at site 1 and removal
      of the 3kDa amino-terminal fragment, rendered site 2 accessible to ICE.
      CONCLUSIONS: The close agreement between the in vitro and modeled behavior of IL
      1beta support our contention that IL-1beta may be structurally related to alpha1
      antitrypsin and also predicts that proIL-1beta requires sequential processing for
      activation. These findings may facilitate the development of novel
      pharmacological agents that control posttranslational proIL-1beta modification,
      thereby preventing excessive production of this potent inflammatory cytokine.

PMID- 11587478
TI  - Receptor-mediated gene targeting to tissues in vivo following intravenous
      administration of pegylated immunoliposomes.
AB  - PURPOSE: Gene therapy has been limited by the immunogenicity of viral vectors, by
      the inefficiency of cationic liposomes, and by the rapid degradation in vivo
      following the injection of naked DNA. The present work describes a new approach
      that enables the non-invasive, non-viral gene therapy of the brain and peripheral
      organs following an intravenous injection. METHODS: The plasmid DNA encoding beta
      galactosidase is packaged in the interior of neutral liposomes, which are
      stabilized for in vivo use by surface conjugation with polyethyleglycol (PEG).
      The tips of about 1% of the PEG strands are attached to a targeting monoclonal
      antibody (MAb), which acts as a "molecular Trojan Horse" to ferry the liposome
      carrying the gene across the biological barriers of the brain and other organs.
      The MAb targets the transferrin receptor, which is enriched at both the blood
      brain barrier (BBB), and in peripheral tissues, such as liver and spleen.
      RESULTS: Expression of the exogenous gene in brain, liver, and spleen was
      demonstrated with beta-galactosidase histochemistry, which showed persistence of
      gene expression for at least 6 days after a single intravenous injection of the
      pegylated immunoliposomes. The persistence of the transgene was confirmed by
      Southern blot analysis. CONCLUSIONS: Widespread expression of an exogenous gene
      in brain and peripheral tissues is induced with a single intravenous
      administration of plasmid DNA packaged in the interior of pegylated
      immunoliposomes. The liposomes are formulated to target specific receptor systems
      that enable receptor-mediated endocytosis of the complex into cells in vivo. This
      approach allows for non-invasive, non-viral gene therapy of the brain.

PMID- 11587479
TI  - Inhibition of HIV-1 in cell culture by oligonucleotide-loaded nanoparticles.
AB  - PURPOSE: To investigate the potential use of polymeric nanoparticles for the
      delivery of antisense oligonucleotides in HIV-1-infected cell cultures. METHODS:
      Phosphorothioate oligonucleotides were encapsulated into poly (D,L-lactic acid)
      nanoparticles. Two models of infected cells were used to test the ability of
      nanoparticles to deliver them. HeLa P4-2 CD4+ cells, stably transfected with the
      beta-galactosidase reporter gene, were first used to evaluate the activity of the
      oligonucleotides on a single-round infection cycle. The acutely infected lymphoid
      CEM cells were then used to evaluate the inhibition of the viral production of
      HIV-1 by the oligonucleotides. RESULTS: The addition to infected CEM cells of
      nanoparticles containing gag antisense oligonucleotides in the nanomolar range
      led to strong inhibition of the viral production in a concentration-dependent
      manner. Similar results were previously observed in HeLa P4-2 CD4+ cells.
      Nanoparticle-entrapped random-order gag oligonucleotides had similar effects on
      reverse transcription. However, the reverse transcriptase activity of infected
      cells treated with nanomolar concentrations of free antisense and random
      oligonucleotides was not affected. CONCLUSIONS: These results suggest that poly
      (D,L-lactic acid) nanoparticles may have great potential as an efficient delivery
      system for oligonucleotides in HIV natural target cells, i.e., lymphocytic cells.

PMID- 11587480
TI  - Characterizing the expression of CYP3A4 and efflux transporters (P-gp, MRP1, and
      MRP2) in CYP3A4-transfected Caco-2 cells after induction with sodium butyrate and
      the phorbol ester 12-O-tetradecanoylphorbol-13-acetate.
AB  - PURPOSE: To examine the changes in expression levels of CYP3A4 and efflux
      transporters in CYP3A4-transfected Caco-2 (colon carcinoma) cells in the presence
      of the inducers sodium butyrate (NaB) and 12-O-tetradecanoylphorbol-13-acetate
      (TPA). To characterize the transport of [3H]-digoxin and the metabolism of
      midazolam in the cells under different inducing conditions. METHODS: CYP3A4-Caco
      2 cells were seeded onto cell culture inserts and were grown for 13-14 days.
      Transport and metabolism studies were performed on cells induced with NaB and/or
      TPA for 24 h. The expression and localization of P-gp, MRP1, MRP2, and CYP3A4
      were examined by Western blot and confocal microscopy. RESULTS: In the presence
      of both inducers, CYP3A4 protein levels were increased 40-fold over uninduced
      cells, MRP2 expression was decreased by 90%, and P-gp and MRP1 expression were
      unchanged. Midazolam 1-OH formation exhibited a rank order correlation with
      increased CYP3A4 protein, whereas [3H]-digoxin transport (a measure of P-gp
      activity) was unchanged with induction. P-gp and MRP2 were found on the apical
      membrane, whereas MRP1 was found perinuclear within the cell. CYP3A4 displayed a
      punctate pattern of expression consistent with endoplasmic reticulum localization
      and exhibited preferential polarization towards the apical side of the cell.
      CONCLUSIONS: The present study characterized CYP3A4-Caco-2 cell monolayers when
      induced for 24 h in the presence of both NaB and TPA. These conditions provide
      intact cells with significant CYP3A4 and P-gp expression suitable for the
      concurrent study of transport and metabolism.

PMID- 11587481
TI  - Transport of peptidomimetic thrombin inhibitors with a 3-amidino-phenylalanine
      structure: permeability and efflux mechanism in monolayers of a human intestinal
      cell line (Caco-2).
AB  - PURPOSE: Peptidomimetic thrombin inhibitors derived from Nalpha-(2
      naphthylsulfonyl)-3-amidino-phenylalanine with different basic and acidic
      substituents were investigated with respect to their intestinal transport
      behavior. METHODS: Intestinal permeability coefficients were studied using Caco-2
      monolayers and a reversed-phase HPLC method for quantitation. RESULTS: Apparent
      permeability coefficients Papp of compounds with a free amidino group were in
      general low (<10 x 10(-8) cm/s) and independent of the structure of the amide
      part (C-terminus). Polarized efflux, however, was strongly affected by
      substituents in the amide moiety yielding the following efflux ratios (ER):
      methylpiperidide (1) (ER 45) > piperidine carboxylic acid methylester (ER 6-11) >
      piperidine carboxylic acids (ER 1.9-2.9) > piperazide (ER -0.17). Efflux of (1)
      was temperature-dependent, but independent of the enantiomeric configuration,
      accompanied by an increase in transepithelial electrical resistance (TEER), and
      could be reduced by P-gp inhibitors (PSC 833, Cremophor EL) but not by
      indomethacin. Replacement of the amidine group of (1) by aminomethyl-, amino-,
      and oxamidine- moieties drastically increased absorptive permeability (46-68
      fold) with ER < 3.4. In contrast, the oxamidine with a C-terminal nipecotic acid
      residue (8) displayed also a temperature dependent efflux- without altering TEER
      (ER 22). This efflux was sensitive to PSC833/Cremophor EL and indomethacin.
      CONCLUSIONS: Basic and acidic residues of amidino-phenylalanine-derived thrombin
      inhibitors mediate affinity to intestinal efflux pumps. presumably P-gp and MRP.
      P-gp mediated efflux was related to a net positive charge and accompanied by an
      increased TEER. Among the methylpiperide (1) promoieties studied the oxamidino
      group seems to be very promising in overcoming both transport and efflux problems
      frequently encountered with peptidomimetics containing amidines.

PMID- 11587482
TI  - Sinusoidal efflux of taurocholate is enhanced in Mrp2-deficient rat liver.
AB  - PURPOSE: It has been shown that plasma concentration and urinary excretion of
      bile acids is elevated under the cholestatic/ hyperbilirubinemic conditions.
      Previously, it was demonstrated that the plasma concentration of bile acids was
      elevated in the multidrug resistance-associated protein 2 (Mrp2)-deficient rats.
      The purpose of the present study was to compare the sinusoidal efflux clearance
      of taurocholate (TC) between Mrp2-deficient Eisai hyperbilirubinemic rats (EHBR)
      and normal rats. METHOD: Hepatic disposition of the [3H]TC was examined in the
      perfused liver. Apparent efflux clearance (PSnet, eff) of [3H]TC from hepatocytes
      to outflow across the sinusoidal membrane was defined as the amount of [3H]TC
      excreted into the outflow from the liver divided by hepatic AUC of [3H]TC.
      Additionally, influx clearance (PSinf) was also determined by multiple indicator
      dilution method because PSnet, eff is also affected by PSinf. RESULTS: PSnet, eff
      was significantly higher in EHBR than that in Sprague-Dawley (SD) rats (16.6 +/-
      1.7 vs. 6.1 +/- 1.3 microL/min/g liver, P < 0.01). In contrast, PSinf was
      comparable between SD rats and EHBR. Kinetic analysis suggested that the
      intrinsic clearance for the efflux of [3H]TC across the sinusoidal membrane in
      EHBR was higher than that in SD rats (10.4 +/- 1.0 v.s. 23.3 +/- 1.7 microL/min/g
      liver, P < 0.01). CONCLUSIONS: Enhanced sinusoidal efflux of TC in EHBR may be
      related to the altered disposition of bile acids in the mutant rats. Because Mrp3
      transports TC and its expression is induced on the basolateral membrane of Mrp2
      deficient rats, the enhanced sinusoidal efflux of TC in EHBR may be accounted
      for, at least partially, by the increased expression of Mrp3.

PMID- 11587483
TI  - Mucosal uptake of gabapentin (neurontin) vs. pregabalin in the small intestine.
AB  - PURPOSE: To compare the mucosal membrane transport of gabapentin and pregabalin
      in animal small intestine. METHODS: Uptake of the two drugs by brush-border
      membrane vesicles (BBMV) from rat and rabbit small intestine was studied as a
      function of temperature, uptake-medium sodium content, and intestinal region.
      Amino acid inhibition studies were conducted with pregabalin. RESULTS: Gabapentin
      uptake by rat and rabbit jejunal BBMV was sodium independent, whereas pregabalin
      uptake was sodium dependent. Uptake of both drugs in rabbit small intestinal
      vesicles was greater at 25 degrees C than at 4 degrees C in the absence of sodium
      and an additional increase in uptake was observed for pregabalin at 25 degrees C
      in the presence of sodium. Pregabalin uptake in rabbit duodenal, jejunal, and
      ileal BBMV was equivalent, whereas gabapentin uptake was greater in duodenal and
      ileal BBMV, compared with jejunal BBMV. Although inhibition is weak, a decrease
      in BBMV uptake of pregabalin is observed with coincubation of high concentrations
      of both neutral and basic amino acids. CONCLUSIONS: Amino acid carriers mediate
      the apical uptake of both drugs in the small intestine. Although gabapentin and
      pregabalin are structurally similar, their small intestinal mucosal uptake
      differs in sodium dependence and region dependence. Gabapentin uptake is likely
      mediated by system b0,+, whereas pregabalin uptake is also mediated by B0 and/or
      B0,+.

PMID- 11587484
TI  - Intestinal first-pass metabolism of eperisone in the rat.
AB  - PURPOSE: The purpose of this study was to clarify quantitatively the contribution
      of the intestine to the first-pass metabolism of eperisone in rats. METHODS: The
      systemic availabilities of eperisone were estimated by administering the drug
      into the duodenum, portal vein, and femoral vein in rats in vivo. The first-pass
      metabolism of eperisone was confirmed in the perfused rat small intestine in
      situ. Metabolism of eperisone to an omega-1-hydroxylated metabolite (HMO), the
      first step of eperisone metabolism, was studied using rat intestinal microsomes
      in vitro. RESULTS: The bioavailabilities in the intestine were 0.176 and 0.0879
      at administration rates of 100 and 25 mg/h/kg, respectively, whereas those in the
      liver were 0.532 and 0.486, respectively. In the intestinal perfusion experiment,
      the appearance clearance to the portal vein from the intestinal lumen was much
      lower than the elimination clearance from the intestinal lumen, resulting in high
      metabolic clearance of eperisone in the small intestine. Eperisone was
      biotransformed to HMO by rat intestinal microsomes, and this was inhibited by
      alpha-naphthoflavone and an anti-rat CYP1A antibody. CONCLUSIONS: Those data
      strongly suggest that eperisone may be metabolized to HMO by CYP1A in rat
      intestinal microsomes during the first-pass through the epithelium of the small
      intestine.

PMID- 11587485
TI  - Transport of lipophilic drug molecules in a new mucus-secreting cell culture
      model based on HT29-MTX cells.
AB  - PURPOSE: A new mucus-secreting in vitro drug absorption model based on monolayers
      of goblet-cell like sub-clones of the human colon carcinoma cell line HT29
      obtained by methotrexate (MTX) treatment was investigated. METHODS: Twelve sub
      clones were isolated and characterized by light microscopy (LM), transelectron
      microscopy (TEM), confocal laser scanning microscopy (CLSM), transepithelial
      electrical resistance (TEER) and the transport of a paracellular marker FITC
      Dextran (Mw 4400) (FD-4). RESULTS: Significant differences of microscopical
      appearance, TEER-values and permeability of FD-4 between the sub-clones were
      evident. However, two of them, namely MTX-D1 and MTX-E12. formed tight confluent
      monolayers with a thick mucus-layer on the apical surface. They were used to
      compare the apparent permeability coefficient (Papp) of a series of lipophilic
      drugs, which should be affected by the mucus-layer, namely barbiturates
      (barbituric acid, barbital, phenobarbital, methylphenobarbital and heptabarbital)
      and testosterone, as a reference, to mucus-free Caco-2 cells. The permeability of
      drugs with a partition coefficient (log P) > 1 was decreased in the mucus
      producing cell lines. Testosterone, the most lipophilic compound, showed a
      decrease of up to 43%. CONCLUSIONS: We demonstrated that the mucus layer is a
      significant barrier to drug absorption for lipophilic drugs. In conclusion, our
      model may serve as a suitable in-vitro cell culture model to study the influence
      of the mucus layer on drug diffusion.

PMID- 11587486
TI  - The effect of polyethylene glycol 400 on gastrointestinal transit: implications
      for the formulation of poorly-water soluble drugs.
AB  - PURPOSE: To assess the effect of polyethylene glycol 400 (PEG 400), a
      pharmaceutical excipient frequently employed to enhance the solubility and
      bioavailability of poorly water-soluble drugs, on the gastrointestinal transit of
      liquid and pellet preparations in human subjects using gamma scintigraphy.
      METHODS: Ten, healthy male volunteers each received, on separate occasions, a
      liquid preparation consisting of 150 ml orange juice (control) or 150 ml orange
      juice containing 10 g PEG 400 (test). Non-disintegrating pellets of size 1.4-1.7
      mm. encapsulated within a hard gelatin capsule, were simultaneously administered
      on both occasions to act as a marker for solid dosage form transit. The liquid
      and pellet preparations were radiolabelled with 111In and 99mTc respectively thus
      enabling their positions within the gastrointestinal tract to be followed using a
      gamma camera. RESULTS: Rapid liquid emptying from the stomach was observed, with
      no significant difference noted in the gastric residence times of the two
      preparations. Caecum arrival times for the liquid preparations were significantly
      different by virtue of their differential rates of transit through the small
      intestine. The mean small intestinal liquid transit time for the control
      preparation was 236 min whereas the corresponding value for the PEG 400
      containing test preparation was 153 min. This 35% reduction in transit time was
      attributed to the presence of PEG 400. Pellet transit was largely unaffected by
      the presence of PEG 400. CONCLUSIONS: These findings clearly demonstrate that PEG
      400 has a marked accelerating effect on small intestinal liquid transit, which in
      turn has implications for the formulation of poorly water-soluble drugs with PEG
      400.

PMID- 11587487
TI  - Transdermal delivery of heparin and low-molecular weight heparin using low
      frequency ultrasound.
AB  - PURPOSE. Heparin and low-molecular weight heparin (LMWH) are the most commonly
      used anticoagulants and are administered by intravenous or subcutaneous
      injections. However, injections of heparin have the potential risk of bleeding
      complications and the requirement of close monitoring in some cases. We
      hypothesized that transdermal delivery of heparin may provide an attractive
      alternative to injections. However, the dose of transdermally delivered heparin
      is limited by low skin permeability. METHODS: We increased skin permeability to
      heparin and LMWH using low-frequency (20 kHz) ultrasound. Biologic activity of
      transdermally delivered heparin was measured by using activated clotting time
      assays and by using anti-Xa (aXa) activity. Structural integrity of heparin was
      also assessed by using gel electrophoresis. RESULTS: Low-frequency ultrasound
      increased permeability of pigskin in vitro and rat skin in vivo and allowed
      delivery of biologically active doses of heparin and low-molecular weight heparin
      transdermally. A prolonged contact of transdermally delivered heparin with
      pigskin was found to reduce the biologic activity of heparin, although no such
      deactivation was observed during short exposures. Transdermally delivered LMWH
      resulted in sustained aXa levels in the blood. This result was in strong contrast
      to subcutaneous or intravenous injections of LMWH, which resulted in only
      temporary elevations of aXa level. CONCLUSIONS: Transdermal delivery of low
      molecular weight heparin is a potential alternative to injections.

PMID- 11587488
TI  - Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier
      for brain delivery.
AB  - PURPOSE: The aim of this study was to evaluate the ability of long-circulating
      PEGylated cyanoacrylate nanoparticles to diffuse into the brain tissue. METHODS:
      Biodistribution profiles and brain concentrations of [14C]-radiolabeled PEG
      PHDCA, polysorbate 80 or poloxamine 908-coated PHDCA nanoparticles, and uncoated
      PHDCA nanoparticles were determined by radioactivity counting after intravenous
      administration in mice and rats. In addition, the integrity of the blood-brain
      barrier (BBB) after nanoparticles administration was evaluated by in vivo
      quantification of the diffusion of [14C]-sucrose into the brain. The location of
      fluorescent nanoparticles in the brain was also investigated by epi-fluorescent
      microscopy. RESULTS: Based on their long-circulating characteristics, PEGylated
      PHDCA nanoparticles penetrated into the brain to a larger extent than all the
      other tested formulations. Particles were localized in the ependymal cells of the
      choroid plexuses, in the epithelial cells of pia mater and ventricles, and to a
      lower extent in the capillary endothelial cells of BBB. These phenomena occurred
      without any modification of BBB permeability whereas polysorbate 80-coated
      nanoparticles owed, in part, their efficacy to BBB permeabilization induced by
      the surfactant. Poloxamine 908-coated nanoparticles failed to increase brain
      concentration probably because of their inability to interact with cells.
      CONCLUSIONS: This study proposes PEGylated poly (cyanoacrylate) nanoparticles as
      a new brain delivery system and highlights two requirements to design adequate
      delivery systems for such a purpose: a) long-circulating properties of the
      carrier, and b) appropriate surface characteristics to allow interactions with
      BBB endothelial cells.

PMID- 11587489
TI  - Inhibitory effects of novel hydrophilic cyclodextrin derivatives on nitric oxide
      production in macrophages stimulated with lipopolysaccharide.
AB  - PURPOSE: The objective of this study is to examine the effects of cyclodextrins
      (CyDs) on nitric oxide (NO) production in macrophages stimulated with
      lipopolysaccharide (LPS). METHODS: RAW264.7 cells, a mouse macrophage-like cell,
      were used. Cytotoxicity of CyDs was evaluated by WST-1 method. Nitrite, iNOS, and
      iNOS mRNA were determined by Griess method, Western blotting, and reverse
      transcription-polymerase chain reaction (RT-PCR) analysis, respectively. The
      interaction of LPS with CyDs was evaluated by utilizing a competitive inclusion
      phenomenon. The binding of FITC-labeled LPS to the surface of RAW264.7 cells was
      measured by a flow cytometry. RESULTS: Of 15 CyDs, 2,6-di-O-methyl-alpha-CyD (DM
      alpha-CyD), and 2,6-di-O-methyl-3-O-acetyl-beta-cyclodextrin (DMA-beta-CyD) had
      greater inhibitory activity than did the other CyDs against NO production in
      RAW264.7 cells stimulated with LPS, without showing any cytotoxicity. DM-alpha
      CyD and DMA-beta-CyD specifically inhibited the increase in iNOS and iNOS mRNA
      levels elicited by stimulation with LPS in RAW264.7 cells. DM-alpha-CyD and DMA
      beta-CyD suppressed the binding of FITC-labeled LPS to the surface of cells,
      probably resulting in inhibitory effects on iNOS expression and NO production. DM
      alpha-CyD had a greater interaction with RAW264.7 cells than did DMA-beta-CyD.
      The pretreatment of RAW264.7 cells with DM-alpha-CyD, not DMA-beta-CyD, decreased
      the LPS binding to the cell surface. The results suggested that the inhibitory
      mechanism of the LPS binding to the cell surface is different between DM-alpha
      CyD and DMA-beta-CyD. CONCLUSIONS: The present results suggest that DM-alpha-CyD
      and DMAbeta-CyD attenuates NO production by inhibiting iNOS gene expression in
      RAW264.7 cells stimulated with LPS, probably due to the suppression of LPS
      binding to LPS receptors on the cells in the different way.

PMID- 11587490
TI  - A pharmacokinetic model to predict the PK interaction of L-dopa and benserazide
      in rats.
AB  - PURPOSE: To study the PK interaction of L-dopa/benserazide in rats. METHODS: Male
      rats received a single oral dose of 80 mg/kg L-dopa or 20 mg/kg benserazide or
      80/20 mg/kg L-dopa/benserazide. Based on plasma concentrations the kinetics of L
      dopa, 3-O-methyldopa (3-OMD), benserazide, and its metabolite Ro 04-5127 were
      characterized by noncompartmental analysis and a compartmental model where total
      L-dopa clearance was the sum of the clearances mediated by amino-acid
      decarboxylase (AADC), catechol-O-methyltransferase and other enzymes. In the
      model Ro 04-5127 inhibited competitively the L-dopa clearance by AADC. RESULTS:
      The coadministration of L-dopa/benserazide resulted in a major increase in
      systemic exposure to L-dopa and 3-OMD and a decrease in L-dopa clearance. The
      compartmental model allowed an adequate description of the observed L-dopa and 3
      OMD concentrations in the absence and presence of benserazide. It had an
      advantage over noncompartmental analysis because it could describe the temporal
      change of inhibition and recovery of AADC. CONCLUSIONS: Our study is the first
      investigation where the kinetics of benserazide and Ro 04-5127 have been
      described by a compartmental model. The L-dopa/benserazide model allowed a
      mechanism-based view of the L-dopa/benserazide interaction and supports the
      hypothesis that Ro 04-5127 is the primary active metabolite of benserazide.

PMID- 11587491
TI  - Effects of food on the pharmacokinetics of methylphenidate.
AB  - PURPOSE: To test the hypothesis that the pharmacokinetics of d-methylphenidate (d
      MPH) would be altered by food ingested before administration of an immediate
      release formulation (dl-MPH- IR) but not when food is ingested before a slow
      release formulation (dl-MPH-SR). METHODS: A randomized, four-phase, open label,
      crossover design was conducted in 24 healthy men who each received, on separate
      occasions, dl-MPH-IR and dl-MPH-SR taken after an overnight fast and 15 min after
      a standardized breakfast (20% protein, 21% fat, 59% carbohydrate). Plasma MPH
      levels were monitored by a validated, stereoselective. GLC-ECD method. RESULTS:
      For plasma d-MPH, there were significant differences (ANOVA) between dl-MPH-IR
      and dl-MPH-SR in tmax, Cmax (peak exposure), and Cmax/AUC (sensitive to rate of
      absorption). Dl-MPH-SR on average delayed tmax from 2.3 to 3.7 h and lowered Cmax
      34%. There was no significant difference between the formulations in AUC (extent
      of absorption). For dl-MPH-IR, food significantly increased Cmax (23%) and AUC
      (15%) and for dl-MPH-SR the corresponding increases were Cmax (17%) and AUC
      (14%). After dl-MPH-IR, food delayed average tmax from 2.0 to 2.5 but had no
      effect on tmax after dl-MPH-SR. There was no effect of food on Cmax/AUC (rate of
      absorption). CONCLUSIONS: Food caused a significant increase in extent of
      absorption but had no effect on rate of absorption of d-MPH after either dl-MPHIR
      or dl-MPH-SR.

PMID- 11587492
TI  - A physiologically based pharmacokinetic analysis of capecitabine, a triple
      prodrug of 5-FU, in humans: the mechanism for tumor-selective accumulation of 5
      FU.
AB  - PURPOSE: To identify the factors governing the dose-limiting toxicity in the
      gastrointestine (GI) and the antitumor activity after oral administration of
      capecitabine, a triple prodrug of 5-FU, in humans. METHOD: The enzyme kinetic
      parameters for each of the four enzymes involved in the activation of
      capecitabine to 5-FU and its elimination were measured experimentally in vitro to
      construct a physiologically based pharmacokinetic model. Sensitivity analysis for
      each parameter was performed to identify the parameters affecting tissue 5-FU
      concentrations. RESULTS: The sensitivity analysis demonstrated that (i) the
      dihydropyrimidine dehydrogenase (DPD) activity in the liver largely determines
      the 5-FU AUC in the systemic circulation, (ii) the exposure of tumor tissue to 5
      FU depends mainly on the activity of both thymidine phosphorylase (dThdPase) and
      DPD in the tumor tissues, as well as the blood flow rate in tumor tissues with
      saturation of DPD activity resulting in 5-FU accumulation, and (iii) the
      metabolic enzyme activity in the GI and the DPD activity in liver are the major
      determinants influencing exposure to 5-FU in the GI. The therapeutic index of
      capecitabine was found to be at least 17 times greater than that of other 5-FU
      related anticancer agents, including doxifluridine, the prodrug of 5-FU, and 5-FU
      over their respective clinical dose ranges. CONCLUSIONS: It was revealed that the
      most important factors that determine the selective production of 5-FU in tumor
      tissue after capecitabine administration are tumor-specific activation by
      dThdPase, the nonlinear elimination of 5-FU by DPD in tumor tissue, and the blood
      flow rate in tumors.

PMID- 11587493
TI  - Kinetic analysis of the disposition of insulin-like growth factor 1 in healthy
      volunteers.
AB  - PURPOSE: Insulin-like growth factor 1 (IGF-1) is predominantly bound to its
      specific binding proteins (IGFBPs) in circulating plasma. In the present study,
      pharmacokinetic analysis of IGF-1 was performed in healthy volunteers to
      characterize the effect of interactions with IGFBPs on IGF-1 disposition.
      METHODS: Plasma concentration profiles of both free and bound IGF-1 were examined
      at several doses. An in vitro plasma protein binding was also analyzed. RESULTS:
      The total body clearance (CLtotal) for the free IGF-1 was much higher than the
      creatinine clearance, suggesting that the major elimination pathway is by a route
      other than renal glomerular filtration. The CLtotal for the free IGF-1 exhibited
      a dose-dependent reduction whereas that for the sum of unbound and bound IGF-1
      increased on increasing the dose. The data obtained fitted closely a one
      compartment model that involved the binding and dissociation of IGF-1, as well as
      its biosynthesis and elimination. The estimated parameters suggest that IGF-1
      exhibits high affinity binding to IGFBPs. the rate-limiting step in the overall
      elimination being the dissociation from IGFBPs. CONCLUSIONS: The saturation of
      both the plasma protein binding and elimination accounts for the nonlinear
      pharmacokinetic profile. The binding to IGFBPs markedly limits both the
      distribution and elimination of IGF-1.

PMID- 11587494
TI  - Modeling and stimulation for clinical trial design involving a categorical
      response: a phase II case study with naratriptan.
AB  - PURPOSE: The overall aim of the present study was to investigate retrospectively
      the feasibility and utility of model-based clinical trial simulation as applied
      to the clinical development of naratriptan with effect measured on a categorical
      scale. METHODS: A PK-PD model for naratriptan was developed by using information
      gathered from previous naratriptan and sumatriptan preclinical and clinical
      trials. The phase IIa naratriptan data were used to check the PK-PD model in its
      ability to describe future data. A further PK-PD model was developed by using the
      phase IIa naratriptan data, and a phase IIb trial was designed by simulation with
      the use of Matlab. The design resulting from clinical trial simulation was
      compared with that derived by using D-optimal design. RESULTS: The PK-PD model
      showed reasonable agreement with the data observed in the phase IIa naratriptan
      clinical trial. Clinical trial simulation resulted in a design with four or five
      arms at 0 mg, 2.5 and/or 5 mg, 10 mg, and 20 mg, PD measurements to be taken at
      0, 2, and 4 or 6 h and at least 150 patients per arm. A sub-D-optimal design
      resulted in two dosing arms at 0 and 10 mg and PD measurements to be taken at 1
      and 2 h. CONCLUSIONS: Clinical trial simulation is a useful tool for the
      quantitative assessment of the influence of the controllable factors and is the
      only tool for the quantitative assessment of the uncontrollable factors on the
      power of a clinical trial.

PMID- 11587495
TI  - Power spectral analysis of heart rate variability in rats as a quantitative tool
      in the PK-PD analysis of the parasympatholytic activity of atropine.
AB  - PURPOSE: To utilize power spectral analysis (PSA) of heart rate variability (HRV)
      as a pharmacodynamic (PD) measure of atropine parasympathetic effect, and to
      model the kinetics of action. METHODS: Heart rate data was collected following
      atropine administration to rats and was analyzed off-line for high frequency
      peaks by PSA of HRV as a measure of parasympathetic tone. A temporal cumulative
      approach (TCA) detected transient changes in parasympathetic activity. The
      pharmacokinetics (PK) was analyzed and linked to both direct and indirect PK-PD
      models. RESULTS: TCA enabled a quantitative measure of atropine parasympathetic
      activity. A simultaneous fit of the indirect PK-PD model to the experimental data
      of all three atropine doses successfully captured the experimental data.
      CONCLUSIONS: TCA can be used as a quantitative measure of parasympathetic tone.
      Our work has established a preclinical model to investigate the kinetics of drug
      action on the autonomic nervous system.

PMID- 11587496
TI  - Osmotic properties of sulfobutylether and hydroxypropyl cyclodextrins.
AB  - PURPOSE: The purpose of this study was to determine the osmolality of
      sulfobutylether (SBE) and hydroxypropyl (HP) derivatives of cyclodextrins (CDs)
      via vapor pressure osmometry (VPO) and freezing point depression (FPD). (SBE) and
      HP-CDs are efficient excipients capable of solubilizing and stabilizing poorly
      water-soluble drugs in parenteral formulations. (SBE)-CDs have also been used as
      solubility enhancers and osmotic agents for the sustained release of poorly water
      soluble drugs from osmotic pump tablets. The knowledge of the CD's osmolality in
      solution or inside such tablets would allow one to further characterize the
      release mechanisms. METHODS: Experiments were conducted at 37 degrees C with
      eight types of HP and (SBE)-CDs. The aqueous solutions ranged from 0.005-0.350
      mol(-1). Methods were developed to allow the measurement of high osmolalities
      using a vapor pressure osmometer or a differential scanning calorimeter. RESULTS:
      The osmolality calculations from the VPO and FPD measurements correlated well.
      The osmolality of (SBE)-CDs was significantly higher than the osmolality of HP
      CDs and increased with the total degree of substitution (TDS). All CDs showed
      deviations from ideality at high concentrations. CONCLUSIONS: Empirical
      correlations of osmolality with concentration and TDS allowed the prediction of
      osmolality over a wide concentration range. This study also gave some useful
      insights into the behavior of CD derivatives in solution.

PMID- 11587497
TI  - Enzymatic activities in the microsomes prepared from rat small intestinal
      epithelial cells by differential procedures.

PMID- 11587498
TI  - Tribute to David E. Barmes.

PMID- 11587499
TI  - A bite too much!

PMID- 11587500
TI  - The specialist list in orthodontics: a postmortem.
AB  - It is now more than one year since the Specialist List in Orthodontics closed on
      30 June 2000. I therefore felt it appropriate that I should give my views on the
      list, having probably had more experience in this process than any other dentist
      in the UK.

PMID- 11587501
TI  - The examination and recording of the occlusion: why and how.
AB  - Before presenting 'how' the examination and recording of the occlusion may be
      achieved, some attempt should be made to justify 'why' it is necessary. It may
      appear to be a strange way of justifying the need to examine the patient's
      occlusion, but this will initially involve a study of the influences of
      mandibular movements.

PMID- 11587502
TI  - The role of removable appliances in contemporary orthodontics.
AB  - The contemporary uses of removable appliances are considerably more limited than
      in the past. This article discusses possible reasons for their declining use,
      including recognition of their limitations. It is possible to achieve adequate
      occlusal improvement with these appliances providing that suitable cases are
      chosen. Specific indications for their appropriate use on their own in the mixed
      dentition are presented. Removables can also be used as an adjunct to more
      complex treatments, to enhance the effect of fixed appliances, headgear or in
      preparation for functional appliances. Further research is required to confirm
      whether their use in conjunction with more complex treatments enhances the
      quality and efficiency of treatment or not.

PMID- 11587503
TI  - Pain control with paracetamol from a sustained release formulation and a standard
      release formulation after third molar surgery: a randomised controlled trial.
AB  - OBJECTIVE: To compare the analgesic efficacy and safety of a sustained release
      (SR) paracetamol formulation (Panadol Extend) with a standard immediate release
      (IR) formulation (Panadol) after third molar surgery. DESIGN: A multi-centre,
      double-blind, randomised clinical trial. METHODS: Patients received either a
      single oral dose of SR paracetamol or IR paracetamol for pain after the removal
      of at least one impacted third molar requiring bone removal under general
      anaesthesia. Post-operative pain and pain relief assessments were undertaken at
      time intervals up to 8 hours. Global assessments of effectiveness were made at 4
      and 8 hours. Any adverse events were also recorded. RESULTS: Of 627 randomised
      patients, 314 were treated with SR paracetamol and 313 with IR paracetamol. In
      the per protocol population at 4 hours, 35.1% of the 252 patients on SR
      paracetamol rated the study medication as very good or excellent compared with
      27.7% of the 258 patients on IR paracetamol. There were few statistically
      significant differences among the secondary parameters but where they did occur
      they favoured SR paracetamol. Trends in favour of SR paracetamol were observed
      among the secondary parameters and these tended to emerge at the later time
      points. For example, while there was no statistically significant difference in
      time to re-medication between the treatment groups, the estimated time to re
      medication was longer for patients treated with SR paracetamol (4 hr 5 min)
      compared with IR paracetamol (3 hr 10 min). The high rate of re-medication
      observed is consistent with that reported for IR paracetamol using the post
      operative dental pain model(4,6). No difference was observed between the SR
      paracetamol and IR paracetamol treatment groups in distribution, incidence or
      severity of adverse events. CONCLUSIONS: SR paracetamol and IR paracetamol are
      clinically and statistically equivalent. While SR paracetamol and IR paracetamol
      were similar in terms of both onset of analgesia and peak analgesic effect, SR
      paracetamol had a longer duration of activity than IR paracetamol. The safety
      profiles of SR paracetamol and IR paracetamol were found to be very similar.

PMID- 11587504
TI  - The relationship between Index of Complexity, Outcome and Need, and patients'
      perceptions of malocclusion: a study in general dental practice.
AB  - AIM: To examine the relationship between the Index of Complexity, Outcome and
      Need (ICON) and the subjective opinions of patients attending for routine dental
      care. MATERIALS AND METHODS: This study was undertaken at two general dental
      practices in Cardiff and Bedford. 50 patients aged between 11-14 years and 50
      patients aged 30-40 years presenting for routine dental treatment were selected
      in each. The subjects were assessed objectively using the ICON guidelines by two
      examiners trained and calibrated in the use of this index. The scores were
      recorded directly from the patient. Subjective assessments were obtained from the
      patients by means of a questionnaire consisting of four simple questions
      addressing aesthetics, function, speech and treatment need using a five point
      Likert scale. RESULTS: The mean ICON scores for the different genders and age
      groups participating in this study were; 11-14 year old males 58.4 (SE 3.17); 11
      14 year old females 51.8 (SE 3.51); 30-40 year old males 51.2 (SE 2.70); 30-40
      year old females 45.3 (SE 2.56). There were statistically significant differences
      in ICON scores between the younger and older groups (P = 0.024) and females and
      males (P = 0.04). Adult patients were more likely to reject treatment than
      younger patients. Analysis of the professional scores in relation to subjective
      assessments, using the Spearman rank correlation coefficient, for 11-14 and 30-40
      year olds, and for the male and female genders, revealed that the ICON has a
      significant correlation with patients' perceptions of aesthetics, function,
      speech and treatment need (r2 = 0.01 to 0.28). The only exceptions were patients'
      perceptions of speech in the 30-40 year old group, and function in the female
      gender, which did not show a statistically significant correlation to the
      professional assessments. CONCLUSION: In this study, the ICON was found to
      correlate with patients' opinions of aesthetics, function, speech and treatment
      need. The strength of association, however, was low. It can be concluded that the
      ICON alone is not necessarily a suitable predictor for appearance, function,
      speech or treatment need for those individuals attending general dental practice
      for routine dental care. In combination with a simple question to assess the
      patients desire for treatment, the shared decision for any particular individual
      to enter the treatment process can be determined.

PMID- 11587505
TI  - Participating dentists' assessment of the pilot regional online videoconferencing
      in dentistry (PROVIDENT) project.
AB  - OBJECTIVE: To assess the educational effectiveness of delivering continuing
      professional education (CPE) from dental schools to small groups of dentists at
      distant sites via videoconferenced links using relatively inexpensive equipment
      and ISDN2 links. DESIGN: 41 videoconferences between the four campuses of London
      Dental Schools and postgraduate centres in South East England were assessed using
      a pre-piloted questionnaire which contained open and specific questions. The
      questionnaire was given to all participants at the end of each videoconference.
      Answers to the specific questions were graded using the Likert scale. RESULTS: 40
      of the 41 videoconferences were completed satisfactorily and were attended by 257
      participants, all of whom completed questionnaires. However, no individual
      question was answered by all the participants. Of the responses 90% were positive
      on the topics of appropriateness of the teaching material for delivery by
      videoconference and of its educational level. 90% of responses also indicated a
      wish to attend further videoconferences and satisfaction at avoiding the need to
      travel to London for similar educational activity. 87% rated the lecturers as
      good or excellent in their use of the medium. 85% of responses indicated that the
      question and answer sessions within the videoconferences were useful and 82% that
      the visual aids enhanced the sessions. The technical aspects of the
      videoconferences were rated positively but to a lesser extent than the
      educational aspects with 69% of positive responses for visibility of visual aids,
      54% for sound quality and 76% for the lecturers use of the technology. The
      technical aspects of the videoconferences improved during the pilot study. In
      response to the open questions, participants stated that they found the most
      useful aspects of the videoconferences were not having to travel, access to first
      rate lecturers, the discussions and the opportunity to interact with experts.
      CONCLUSIONS: The participants in this pilot study were positive about the use of
      videoconferencing to deliver educational material from dental schools to small
      groups. Once the technology has improved, this medium has the potential to
      provide CPE for dentists at work or at home in response to their specific needs.

PMID- 11587506
TI  - Molecular analysis of the Doppia transposable element of maize.
AB  - Doppia (Dop) transposable elements were first identified from element termini
      found in the upstream portions of certain alleles of the pl1 and r1 loci of
      maize. At the r1 locus, these Dop end sequences are present in a region called
      sigma, which functions as the promoter for the S genes of the R-r haplotype, and
      which is required for efficient epigenetic modification of the S genes during
      paramutation. In order to better understand the significance of the Dop element
      sequences at R-r, and to investigate the Dop-encoded products that might regulate
      r1 genes in this haplotype, we have cloned a more complete Dop element, Dop4. The
      Dop4 element can encode two proteins that have strong sequence similarity to the
      TnpA and TnpD proteins of the well characterized maize transposable element
      En/Spm. The DOPA protein, which is similar to TnpA of En/Spm, is shown to bind to
      short, subterminal repeat motifs located in the Dop element ends. Like TnpA, DOPA
      promotes intermolecular associations between DNA molecules. In contrast to the
      activity of TnpA, which is a transcriptional repressor of En/Spm, DOPA activates
      expression of reporter genes driven by either the Dop promoter or sigma in
      transient expression assays.

PMID- 11587507
TI  - Analysis of barley chloroplast psbD light-responsive promoter elements in
      transplastomic tobacco.
AB  - The plastid gene psbD encodes D2, a photosystem II reaction center chlorophyll
      binding protein. psbD is transcribed from a conserved chloroplast promoter that
      is activated by blue, white, or UV-A light. In this study, various forms of the
      barley (Hordeum vulgare L.) chloroplast psbD-LRP were fused to the uidA reporter
      gene and introduced into the tobacco (Nicotiana tabacum L.) plastid genome
      through homologous recombination. Primer extension analysis of transcripts from
      the psbD-LRP-uidA construct showed that the barley psbD-LRP was activated in
      tobacco by blue or white light. Transcription from this construct was also
      regulated by circadian cycling indicating that the barley psbD-LRP could respond
      to light modulated regulatory pathways in tobacco. Mutation of the psbD-LRP
      prokaryotic -10 promoter element reduced transcription to very low levels in all
      light regimes. In contrast, mutation of a prokaryotic -35 promoter element had no
      effect on transcription from the psbD-LRP. Deletion or mutation of an upstream
      activating element, the AAG-box (-36 to -64), also reduced transcription from the
      construct to very low levels. In contrast, deletion of the upstream PGT-box (-71
      to -100) did not alter promoter activation by blue light, or responsiveness to
      circadian cycling. These in vivo studies confirm the importance of the psbD-LRP 
      10 promoter element and AAG-box in light regulation and demonstrate that these
      elements are sufficient to mediate circadian cycling of the barley psbD promoter.

PMID- 11587508
TI  - The transcript abundance of GmGT-2, a new member of the GT-2 family of
      transcription factors from soybean, is down-regulated by light in a phytochrome
      dependent manner.
AB  - A new member of the GT-2 family of transcription factors, GmGT-2, was isolated
      from soybean while screening a cDNA library with a protein binding site (D1) in
      the promoter of Aux28, a member of the Aux/IAA family of auxin-responsive genes.
      GmGT-2 possesses various primary amino acid sequence characteristics common to
      all GT-2 factors thus far isolated, including sequence identity in the twin
      trihelix DNA-binding domains. Recombinant GmGT-2 expressed in Escherichia coli
      binds oligotetramers of both D1 and various GT-boxes. However, unlike other known
      members of the GT-2 family, GmGT-2 message levels are down-regulated by light in
      a phytochrome-dependent manner. Evidence is presented that the expression levels
      of Aux28 mRNA are also down-regulated by phytochrome. These results and other
      referenced data implicate the possible convergence of phytochrome and auxin
      signaling pathways.

PMID- 11587509
TI  - Characterization of a second carotenoid beta-hydroxylase gene from Arabidopsis
      and its relationship to the LUT1 locus.
AB  - Xanthophylls are oxygenated carotenoids that perform critical roles in plants.
      Beta-carotene hydroxylases (beta-hydroxylases) add hydroxyl groups to the beta
      rings of carotenes and have been cloned from several bacteria and plants,
      including Arabidopsis. The lut1 mutation of Arabidopsis disrupts epsilon-ring
      hydroxylation and has been suggested to identify a related carotene hydroxylase
      that functions specifically on epsilon-ring structures. We have used library
      screening and genomics-based approaches to isolate a second beta-hydroxylase
      genomic clone and its corresponding cDNA from Arabidopsis. The encoded protein is
      70% identical to the previously reported Arabidopsis beta-hydroxylase 1.
      Phylogenetic analysis indicates a common origin for the two proteins, however,
      their different chromosomal locations, intron positions and intron sizes suggest
      their duplication is not recent. Although both hydroxylases are expressed in all
      Arabidopsis tissues analyzed, beta-hydroxylase 1 mRNA is always present at higher
      levels. Both cDNAs encode proteins that efficiently hydroxylate the C-3 position
      of beta-ring containing carotenes and are only weakly active towards epsilon-ring
      containing carotenes. Neither beta-hydroxylase cDNA maps to the LUT1 locus, and
      the genomic region encompassing the LUT1 locus does not contain a third related
      hydroxylase. These data indicate that the LUT1 locus encodes a protein necessary
      for epsilon-ring hydroxylation but unrelated to beta-hydroxylases at the level of
      amino acid sequence.

PMID- 11587510
TI  - Temporal and spatial expression patterns of TUB9, a beta-tubulin gene of
      Arabidopsis thaliana.
AB  - Transgenic plants carrying chimeric genes composed of segments of the 5'-flanking
      region of the Arabidopsis 9-tubulin gene (TUB9) fused to the coding region of the
      beta-glucuronidase (GUS) gene of Escherichia coli were used to investigate the
      temporal and spatial patterns of TUB9 expression. Chimeric genes that contained
      at least 800 bp of TUB9 5'-flanking DNA were expressed primarily in floral
      tissues, with high levels of expression observed in pollen, elongating pollen
      tubes and ovules. The expression of the reporter genes in ovules ceased at the
      time of fertilization. In situ hybridization was used to verify that the reporter
      gene expression in pollen of transgenic plants is representative of the patterns
      of expression of the endogenous TUB9 gene. In situ hybridization also provided
      new insight into TUB9 transcript accumulation in ovules. The possible role of
      TUB9 and the functional implication of the largely non-overlapping expression
      patterns of tubulin genes are discussed.

PMID- 11587511
TI  - Promoters for pregenomic RNA of banana streak badnavirus are active for transgene
      expression in monocot and dicot plants.
AB  - Two putative promoters from Australian banana streak badnavirus (BSV) isolates
      were analysed for activity in different plant species. In transient expression
      systems the My (2105 bp) and Cv (1322 bp) fragments were both shown to have
      promoter activity in a wide range of plant species including monocots (maize,
      barley, banana, millet, wheat, sorghum), dicots (tobacco, canola, sunflower,
      Nicotiana benthamiana, tipu tree), gymnosperm (Pinus radiata) and fern
      (Nephrolepis cordifolia). Evaluation of the My and Cv promoters in transgenic
      sugarcane, banana and tobacco plants demonstrated that these promoters could
      drive high-level expression of either the green fluorescent protein (GFP) or the
      beta-glucuronidase (GUS) reporter gene (uidA) in vegetative plant cells. In
      transgenic sugarcane plants harbouring the Cv promoter, GFP expression levels
      were comparable or higher (up to 1.06% of total soluble leaf protein as GFP) than
      those of plants containing the maize ubiquitin promoter (up to 0.34% of total
      soluble leaf protein). GUS activities in transgenic in vitro-grown banana plants
      containing the My promoter were up to seven-fold stronger in leaf tissue and up
      to four-fold stronger in root and corm tissue than in plants harbouring the maize
      ubiquitin promoter. The Cv promoter showed activities that were similar to the
      maize ubiquitin promoter in in vitro-grown banana plants, but was significantly
      reduced in larger glasshouse-grown plants. In transgenic in vitro-grown tobacco
      plants, the My promoter reached activities close to those of the 35S promoter of
      cauliflower mosaic virus (CaMV), while the Cv promoter was about half as active
      as the CaMV 35S promoter. The BSV promoters for pregenomic RNA represent useful
      tools for the high-level expression of foreign genes in transgenic monocots.

PMID- 11587512
TI  - Visualization of the terminal structure of rice chromosomes 6 and 12 with
      multicolor FISH to chromosomes and extended DNA fibers.
AB  - High-resolution fluorescence in situ hybridization (FISH) on interphase and
      pachytene nuclei, and extended DNA fibers enabled microscopic distinction of DNA
      sequences less than a few thousands of base pairs apart. We applied this
      technique to reveal the molecular organization of telomere ends in japonica rice
      (Oryza sativa ssp. japonica), which consist of the Arabidopsis type TTTAGGG
      heptameric repeats and the rice specific subtelomeric tandem repeat sequence A
      (TrsA). Southern hybridizations of DNA digested with Bal31 and EcoRI, and FISH on
      chromosomes and extended DNA fibers demonstrated that (1) all chromosome ends
      possess the telomere tandem repeat measuring 3-4 kb; (2) the subtelomeric TrsA
      occurs only at the ends of the long arms of chromosomes 6 and 12, and measure 6
      and 10 kb, which corresponds to 231 and 682 copies for these sites, respectively;
      (3) the telomere and TrsA repeats are separated by at most a few thousands of
      intervening nucleotide sequences. The molecular organization for a general
      telomere organization in plant chromosomes is discussed.

PMID- 11587513
TI  - Isolation of the first putative peroxidase cDNA from a conifer and the local and
      systemic accumulation of related proteins upon pathogen infection.
AB  - Peroxidases are associated with the active defence reactions in higher plants in
      response to foreign organisms. They are involved in the oxidation of phenolic
      compounds in cell walls, polymerization of lignin and suberin, and in several
      other oxidation processes but the exact function of individual peroxidases is not
      known. We have isolated a cDNA encoding the putative defence-related and basic
      plant peroxidase SPI2 (spruce pathogen-induced 2), with an estimated molecular
      mass of 34 kDa, from roots of Norway spruce (Picea abies) seedlings. This is the
      first description of the isolation of a complete cDNA encoding a putative
      peroxidase from a gymnosperm. The transcript was present in the roots of healthy
      seedlings, and during infection with the pathogen Pythium dimorphum there was a
      rapid initial increase followed by a dramatic reduction of the transcript. The 34
      kDa mature SPI2 protein was detected in both the developing root and shoot of
      healthy seedlings and increased amounts of SPI2 and increased accumulation of
      highly basic peroxidase isoforms was observed in roots after infection. In
      addition, two SPI2-related proteins with apparent molecular masses of 38 and 39
      kDa, were also detected. Both these proteins accumulated in roots only after
      infection, and the 39 kDa protein was in addition detected in shoots of root
      infected seedlings. Thus, both SPI2 and the SPI2-related proteins accumulate as a
      local response, in roots, and as a systemic response to infection the 39 kDa
      protein accumulates in the shoot.

PMID- 11587514
TI  - Dissection of abscisic acid signal transduction pathways in barley aleurone
      layers.
AB  - Abscisic acid (ABA) induces genes that are highly expressed during late
      embryogenesis, but suppresses gibberellin (GA)-responsive genes essential for
      seed germination and seedling growth. Promoter elements necessary and sufficient
      for ABA up- and down-regulation of gene expression have been previously defined
      in barley aleurone layers. We have studied the effect of a protein phosphatase
      2C, ABI1, an ABA-inducible protein kinase, PKABA1, and a transcription factor,
      VP1, on ABA action in a barley aleurone transient expression system. The
      observations have allowed us to dissect ABA signal transduction pathways leading
      to either induction or suppression of gene expression. The ABA induction of
      embryogenesis genes is highly inhibited in the presence of a mutated protein
      phosphatase 2C, encoded by the abi1-1 dominant mutant gene that is known to block
      ABA responses in Arabidopsis. However, the abi1-1 gene product has no effect on
      the ABA suppression of a GA-responsive alpha-amylase gene. On the other hand,
      PKABA1 suppresses the expression of alpha-amylase genes, but has little effect on
      ABA up-regulated genes. Therefore, it appears that ABA induction and suppression
      follow two separate signal transduction pathways with the former inhibited by
      ABI1 and the latter modulated by PKABA1. The presence of VP1 enhances the ABA
      induction of late embryogenesis genes, but also suppresses germination specific
      genes. A schematic model based on these observations is presented to explain the
      effect of these regulatory proteins on ABA-mediated gene expression.

PMID- 11587516
TI  - Imaging assessment of anterior knee pain and patellar maltracking.
AB  - Anterior knee pain is a common complaint in the orthopaedic clinic. The
      differential diagnosis is wide and the principal goal of initial assessment is to
      detect remediable causes. The majority of patients do not have a specific disease
      and increasingly interest has focused on the role of patello-femoro-tibial
      morphology and of patellar maltracking in the aetiology of anterior knee pain.
      Classification in this group of patients is poor and there is no uniform
      agreement on which patient groups benefit from treatment and which treatment is
      best. Much of the literature involves relatively small numbers of patients, is
      poorly controlled and there is little agreement on outcome measures. The purpose
      of this review is to outline the current status of the imaging assessment of
      recalcitrant anterior knee pain with particular reference to patellar
      maltracking.

PMID- 11587515
TI  - RNA polymerase I holoenzyme-promoter complexes include an associated CK2-like
      protein kinase.
AB  - In eukaryotes, RNA polymerase I (pol I) transcribes the tandemly repeated genes
      that encode the precursor of 18S, 5.8S and 25S ribosomal RNAs. In plants and
      animals, the pol I enzyme can be purified in a holoenzyme form that is self
      sufficient for promoter binding and accurate, promoter-dependent transcription in
      a cell-free system. In this report, we show that a casein kinase 2 (CK2)-like
      protein kinase co-purifies with pol I holoenzyme activity purified from broccoli
      (Brassica oleracea). Using an immobilized template assay, we show that the CK2
      like activity is part of the protein-DNA complex that results upon binding of the
      holoenzyme to the rRNA gene promoter. The CK2 activity phosphorylates a similar
      set of holoenzyme proteins both before and after promoter binding. These data
      provide further evidence that pol I holoenzyme activity can be attributed to a
      single, multi-protein complex self-sufficient for promoter association and
      accurate, promoter-dependent transcription.

PMID- 11587517
TI  - Magnetic resonance imaging of bone marrow changes in Gaucher disease during
      enzyme replacement therapy: first German long-term results.
AB  - OBJECTIVE: Since 1991, enzyme replacement therapy (ERT) has been available for
      patients with Gaucher disease in Germany. The aim of this study was to analyse
      the MR pattern of bone marrow involvement and response to ERT in Gaucher disease
      type I. PATIENTS AND DESIGN: Thirty patients with Gaucher disease type I had MRI
      examinations prior to initiation of ERT with alglucerase/imiglucerase and during
      follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1-
      and T2-weighted spin-echo images of the lower extremities were obtained to
      evaluate changes in the appearance of yellow marrow. MR images were categorized
      as having either a homogeneous (type A) or non-homogeneous patchy (type B)
      appearance of bone involvement and response to ERT was assessed by two
      radiologists. RESULTS: Overall, 19 of 30 patients (63%) showed an increased
      signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent
      with partial reconversion of fatty marrow during treatment. Focal bone lesions
      surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting
      bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had
      the non-homogeneous type B pattern (P=0.0021). In 86% of patients with
      splenectomy, bone infarcts were seen (P<0.05). CONCLUSIONS: MRI using T1- and T2
      weighted spin-echo sequences is a valuable, non-invasive method for monitoring
      bone marrow response in patients receiving ERT. A non-homogeneous patchy signal
      intensity of bone marrow involvement correlates with the presence of bone
      infarcts (P=0.0021).

PMID- 11587518
TI  - Acute paediatric ankle trauma: MRI versus plain radiography.
AB  - OBJECTIVE: To evaluate the diagnosis of acute physeal ankle fractures on plain
      radiographs using MRI as the gold standard. METHODS: Sixty consecutive children,
      29 with a clinical diagnosis of lateral ligament injury and 31 with physeal ankle
      fractures, were examined using both radiographs and MRI in the acute period. The
      imaging data were reviewed by three "masked" radiologists. The fracture diagnosis
      and Slater-Harris classification of radiographs were compared with findings on
      MRI. RESULTS: Plain radiography produced five of 28 (18%) false negative and 12
      of 92 (13%) false positive fracture diagnoses compared with MRI. Six of the 12
      false positive fractures were due to a misclassification of lateral ligament
      disruption as SH1 fractures, Altogether a difference was found in 21% of cases in
      either the diagnosis or the classification of the fractures according to Salter
      Harris. All bone bruises in the distal tibia and fibula and 64% of bone bruises
      in the talus were seen in association with lateral ligament injuries. Talar bone
      bruises in association with fractures occurred on the same side as the malleolar
      fracture; talar bone bruises in association with lateral ligament disruption were
      seen in different locations. The errors identified on radiographs by MRI did not
      affect the management of the injury. CONCLUSIONS: The incidence of false negative
      ankle fractures in plain radiographs was small and no complex ankle fractures
      were missed on radiographs. The total extent of complex fractures was, however,
      not always obvious on radiographs. In an unselected series of relatively mild
      ankle injuries, we were unable to show a single case where the treatment or
      prognosis based on plain radiography should have been significantly altered after
      having done a routine MRI examination. Plain radiography is still the diagnostic
      cornerstone of paediatric ankle injuries.

PMID- 11587519
TI  - Pseudotumor deltoideus: a previously undescribed anatomic variant at the deltoid
      insertion site.
AB  - A spectrum of eccentric bone irregularities were observed in the humeral deltoid
      tuberosity region of five patients. Patients were referred for associated pain or
      for the incidental radiographic findings. The lesions are characterized
      radiographically by a relative lucency at or adjacent to the deltoid tuberosity,
      variably increased uptake on the bone scan, and mild cortical irregularity or
      adjacent eccentric marrow abnormality on MRI and CT. The term pseudotumor
      deltoideus is coined for these previously undescribed anatomic variants. Imaging
      studies and extended clinical follow-up in these patients support an inactive or
      indolent process that may be managed conservatively. The potential etiology and
      role of these cortical irregularities as tumor simulators is emphasized.

PMID- 11587520
TI  - The normal development of tibial torsion.
AB  - OBJECTIVE: Pathological rotation of the leg is a well-known problem in paediatric
      orthopaedics. In this study the normal development of tibial torsion during
      growth was evaluated by computed tomography (CT). DESIGN: Seventy-eight normal
      individuals (52 children, 26 adults) aged 3-51 years were examined with CT. In
      axial scans the angle between a line tangential to the posterior part of the
      femoral condyles and the intermalleolar line, a line through the centre of the
      lateral and medial malleolus, was measured. The radiation exposure was evaluated
      and accepted by The National Department for Radiation and the Regional Committee
      for Ethics in Science. RESULTS: CT showed that the average lateral torsion of the
      leg at the age of 4 years was 28 degrees with an individual variation of 20
      degrees-37 degrees. Later the increase in tibial torsion was on average 1
      degrees/year until 10 years of age and, thereafter, 4 degrees until maturity when
      the mean lateral torsion was 38 degrees (18 degrees-47 degrees). CONCLUSION:
      Tibial torsion in children mainly develops during the first 4 years of life.
      After this the increase was of less clinical significance.

PMID- 11587521
TI  - Spontaneous progression of vertebral intraosseous pneumatocysts to fluid-filled
      cysts.
AB  - Intraosseous pneumatocyst is a relatively rare condition, and its natural course
      is not known. We report two cases of intraosseous pneumatocyst of vertebra with
      resorption of gas and its replacement with fluid shown on follow-up cross
      sectional imaging. The mechanism influencing the course of these appearances is
      unclear. However, the benign nature of intraosseous pneumatocyst needs to be
      recognized and biopsy avoided.

PMID- 11587522
TI  - Solitary osteosclerotic plasmacytoma: association with demyelinating
      polyneuropathy and amyloid deposition.
AB  - A 51-year-old man presented with a 1-year history of polyneuropathy necessitating
      the use of a wheelchair. Initial diagnosis was idiopathic chronic inflammatory
      demyelinating polyneuropathy (CIDP) and associated monoclonal gammopathy.
      Investigations for multiple myeloma, including bone marrow aspiration and biopsy,
      were negative. What was initially felt to be an incidental osteosclerotic focus
      noted on the radiographic bone survey was eventually shown to be a solitary
      osteosclereotic plasmacytoma with associated amyloid. This dramatically altered
      treatment. This case emphasizes the importance of including osteosclerotic
      plasmacytoma in the differential diagnosis of a focal sclerotic bone lesion in
      the clinical setting of polyneuropathy. These lesions are less likely to progress
      to multiple myeloma than lytic plasma cell neoplasms, and the presence of
      polyneuropathy often results in earlier diagnosis and treatment with enhanced
      prospect of cure. The finding of amyloid deposition within the osteosclerotic
      lesion may be of prognostic importance.

PMID- 11587523
TI  - Primary leiomyosarcoma of the patella.
AB  - We report on a case of primary leiomyosarcoma of the patella in a 59-year-old
      woman. To our knowledge, this is the first report of this rare tumor in a bone
      where malignant lesions rarely occur.

PMID- 11587524
TI  - Primary mixed tumor of bone.
AB  - Mixed tumors occur most commonly in major salivary glands. They may rarely appear
      in other sites, such as skin, breast, and lung. There have been rare reports of
      similar tumors occurring in bone. We report on a patient with a primary mixed
      tumor of bone. No other primary site has become apparent on follow-up of 5 years.
      Although mixed tumors detected by bone biopsy are likely to be metastatic, they
      may rarely represent primary bone neoplasms.

PMID- 11587525
TI  - Differential regulation of interleukin-12 and interleukin-10 by heat shock
      response in murine peritoneal macrophages.
AB  - Heat shock response is a conserved stress response and has been shown to have
      anti-inflammatory effects. We investigated the effect of heat shock response on
      LPS-induced production of IL-12 and IL-10, which are two important cytokines
      playing contradictory roles in regulation of immune response, by murine
      peritoneal macrophages. The data showed that induction of heat shock response
      strongly suppressed LPS-induced production of IL-12 while augmented that of IL
      10, suggesting the pleiotropic effects of heat shock response on immune
      regulatory gene expression. Also, the novel observation on up-regulation of IL-10
      by heat shock response adds to the mechanism by which heat shock response exerts
      its anti-inflammatory effects.

PMID- 11587526
TI  - The N-terminal domain of the yeast permease Bap2p plays a role in its
      degradation.
AB  - The amino acid permease Bap2p in Saccharomyces cerevisiae mediates a major part
      of the uptake of leucine, isoleucine, and valine from media containing a
      preferred nitrogen source. Although the transcriptional controls of BAP2 have
      been well studied, the posttranslational down-regulation mechanisms for Bap2p
      have not been established. Here we show that Bap2p is subject to a starvation
      induced degradation upon rapamycin treatment or cultivation with proline as the
      sole nitrogen source. The starvation-induced degradation of Bap2p was dependent
      on the cellular functions of ubiquitination and endocytosis. Down-regulation of
      the permease required the most probable ubiquitination sites, the lysine residues
      situated in the N-terminal 49 residues, as well as the C-terminal domain.
      Furthermore, when the N-terminal domain of Bap2p was fused to the general amino
      acid permease Gap1p, the resultant chimeric permease became susceptible to the
      starvation-induced degradation, indicating that the Bap2p N-terminus contains a
      determinant responsive to the starvation signals.

PMID- 11587527
TI  - Expression of a novel human ornithine decarboxylase-like protein in the central
      nervous system and testes.
AB  - Ornithine decarboxylase (ODC) is the key enzyme of polyamine synthesis. The
      physiological activity of ODC is associated with cell proliferation, and high ODC
      activities are encountered in rapidly growing cancer cells. We have cloned a cDNA
      for a novel human protein that is 54% identical to ODC and 45% identical to
      antizyme inhibitor (AZI). mRNA for ODC-paralogue (ODC-p) was found only in the
      central nervous system and testes, suggesting a role in terminal differentiation
      rather than cell proliferation. ODC-p occurs at least in eight alternatively
      spliced forms. In vitro translated ODC-p did not decarboxylate ornithine,
      whereas, in vivo, one splice variant exerted modest ODC-like activity upon
      expression in COS-7 cells. ODC-p has a unique mutation in cysteine 360, where
      this ornithine decarboxylase reaction-directing residue is substituted by a
      valine. This substitution might lead to an enzymatic reaction that differs from
      typical ODC activity. ODC-p might also function as a brain- and testis-specific
      AZI.

PMID- 11587528
TI  - Concordant mRNA expression of UCP-3, but not UCP-2, with mitochondrial
      thioesterase-1 in brown adipose tissue and skeletal muscle in db/db diabetic
      mice.
AB  - A recent hypothesis concerning the function of uncoupling protein-3 (UCP-3)
      depends upon a positive relationship with mitochondrial thioesterase (MTE-1) in
      situations where fatty acid beta-oxidation is increased. MTE-1 mRNA levels are
      raised in transgenic mice overexpressing UCP-3 in skeletal muscle and we sought
      to extend these findings by quantifying in vivo expression of endogenous MTE-1,
      UCP-1, UCP-2, and UCP-3 mRNA levels in white adipose tissue, interscapular brown
      adipose tissue, and skeletal muscle in db/db mice. In this study we show that
      changes in MTE-1 mRNA levels as a result of differences between db/db vs db/+
      mice or following long-term treatment of db/db mice with rosiglitazone or Wy
      14,643 were more closely correlated with changes in UCP-3 than either UCP-1 or
      UCP-2 mRNA levels in the tissues examined. The present data contribute to the
      argument that UCP-3 and MTE-1 are linked within the same metabolic pathway either
      in response to, or as regulators of, fatty acid beta-oxidation.

PMID- 11587529
TI  - Apoptosis is associated with modifications of bcl-2 mRNA AU-binding proteins.
AB  - The expression of genes requiring finely tuned control is regulated by a
      posttranscriptional mechanism involving mRNA A + U-rich elements (AREs)
      cooperating with ARE-binding proteins (AUBPs) in modulation of mRNA stability. We
      reported previously that an ARE in the bcl-2 mRNA 3'-untranslated region (3'-UTR)
      had destabilizing activity and was involved in bcl-2 downregulation during
      apoptosis in vitro. Here we demonstrate that the bcl-2 ARE complexes with a
      number of specific AUBPs, whose pattern undergoes changes following application
      of apoptotic stimuli. The caspase inhibitor Z-VAD-fmk strongly attenuates both
      bcl-2 mRNA decay and bcl-2 AUBP pattern changes elicited by apoptotic stimuli,
      indicating the involvement of bcl-2 AUBPs in bcl-2 mRNA stability control.

PMID- 11587530
TI  - Bidirectional regulation of mitochondrial gene expression during developmental
      neuroplasticity of visual cortex.
AB  - The first several months of life are a critical period for neuronal plasticity in
      the visual cortex, during which anatomical and physiological development depends
      upon visual experience. Rearing in darkness slows the time course of this
      critical period, such that at 5 weeks normal cats are more plastic than dark
      reared cats, while at 20 weeks dark-reared cats are more plastic. This study
      reports the identification of a subset of mitochondrial genes that are regulated
      in this manner. Opponent patterns of bidirectional expression were found: several
      genes (ATPase 6, cytochrome b, NADH dehydrogenase subunits 4 and 2) showed
      elevation in normal cats at 5 weeks and in dark-reared cats at 20 weeks
      ("plasticity" genes); others (NADH dehydrogenase subunits 3 and 5) showed the
      opposite ("anti-plasticity" genes). These findings add a new dimension to the
      growing evidence that changes in mitochondrial gene expression are involved in
      the neuroplastic response.

PMID- 11587531
TI  - Human Scythe contains a functional nuclear localization sequence and remains in
      the nucleus during staurosporine-induced apoptosis.
AB  - Human Scythe (also known as BAT3) has been implicated in the control of apoptosis
      and regulating heat shock protein (HSP) 70 activity. We have attempted to further
      characterize the role of human Scythe in HeLa cells by studying the cellular
      localization and functional domains of a hemagglutinin (HA) epitope-tagged Scythe
      protein. Several HA-Scythe deletion mutant proteins were expressed in HeLa cells
      and their localization was detected using indirect immunofluorescence. Our data
      demonstrate that full-length human Scythe is a nuclear protein that contains an
      active C-terminal nuclear localization sequence (NLS). Site-directed mutagenesis
      of the NLS leads to complete nuclear exclusion of full-length Scythe.
      Furthermore, induction of apoptosis by staurosporine does not cause
      redistribution or cleavage of Scythe, suggesting that Scythe remains localized in
      the nucleus during apoptosis. These results provide evidence that Scythe is a
      nuclear protein that probably does not interact with elements of the apoptotic
      machinery in the cytosol.

PMID- 11587532
TI  - The PUB domain: a putative protein-protein interaction domain implicated in the
      ubiquitin-proteasome pathway.
AB  - Cytoplasmic peptide:N-glycanase (PNGase) is a de-N-glycosylating enzyme which may
      be involved in the proteasome-dependent pathway for degradation of misfolded
      glycoproteins formed in the endoplasmic reticulum (ER) that are exported into the
      cytoplasm. A cytoplasmic PNGase found in Saccharomyces cerevisiae, Png1p, is
      widely distributed in higher eukaryotes as well as in yeast (Suzuki, T., et al.
      J. Cell Biol. 149, 1039-1051, 2000). The recently uncovered complete genome
      sequence of Arabidopsis thaliana prompted us to search for the protein homologue
      of Png1p in this organism. Interestingly, when the mouse Png1p homologue sequence
      was used as a query, not only a Png1p homologue containing a transglutaminase
      like domain that is believed to contain a catalytic triad for PNGase activity,
      but also four proteins which had a domain of 46 amino acids in length that
      exhibited significant similarity to the N-terminus of mouse Png1p were
      identified. Moreover, three of these homologous proteins were also found to
      possess a UBA or UBX domain, which are found in various proteins involved in the
      ubiquitin-related pathway. We name this newly found homologous region the PUB
      (Peptide:N-glycanase/UBA or UBX-containing proteins) domain and propose that this
      domain may mediate protein-protein interactions.

PMID- 11587533
TI  - Functional characterization of cysteinyl leukotriene CysLT(2) receptor on human
      coronary artery smooth muscle cells.
AB  - Cysteinyl leukotrienes (LTC(4), LTD(4), and LTE(4)) are a class of biologically
      active lipids that exert potent effects on the heart. To assess their roles, we
      investigated the distribution of their receptors, CysLT(1) and CysLT(2), in the
      cardiovascular system. CysLT(2) mRNA was detected at high levels in the human
      atrium and ventricle and at intermediate levels in the coronary artery, whereas
      CysLT(1) mRNA was barely detected. Further analysis by in situ hybridization
      revealed that CysLT(2) mRNA was expressed in myocytes, fibroblasts, and vascular
      smooth muscle cells, but not in endothelial cells. When human coronary smooth
      muscle cells were stimulated with LTC(4), the intracellular calcium concentration
      increased in a dose-dependent manner, and this action was partially inhibited by
      nicardipine. Additionally, these cells showed chemotactic responses to LTC(4).
      This is the first report on the physiological role of CysLT(2), and the findings
      suggest that CysLT(2) has biological significance in the cardiovascular system.

PMID- 11587534
TI  - Localization of mitochondrial Hsp56 chaperonin during sea urchin development.
AB  - We have previously demonstrated that Paracentrotus lividus nuclear genome encodes
      for the heat shock inducible chaperonin homolog Hsp 56 (1) and that the mature
      protein is localized in the mitochondrial matrix (2). In this paper we report
      that constitutive Hsp56 is maternally inherited, in fact it is present in the in
      unfertilized eggs, and that it has a perinuclear specific localization during
      cleavage. In the later stages both the constitutive and the heat shock inducible
      chaperonin has a specific territorial distribution. Moreover following heat
      shock, the Hsp56 appears in the cytoplasm and in the postmitochondrial
      supernatant beside the mitochondrial fraction.

PMID- 11587535
TI  - RNAi in mouse oocytes and preimplantation embryos: effectiveness of hairpin
      dsRNA.
AB  - RNA interference (RNAi), the targeted mRNA degradation by double-stranded RNA
      (dsRNA), is a useful tool for studying gene function in several organisms. Here
      we report results of experiments with mammalian dsRNA expression vectors that are
      suitable to study gene function in mouse oocytes and preimplantation embryos. The
      plasmid vectors were constructed to contain the SV40 small intron, EGFP coding
      sequence to permit detection of expression, and an inverted repeat to mos mRNA
      that would form a hairpin dsRNA. Results of the experiments indicated that (i)
      hairpin dsRNA was just as effective as dsRNA (i.e., annealed sense and antisense
      RNA) in promoting the destruction of targeted mRNA, (ii) the EGFP marker could be
      expressed from the construct, and (iii) the distance of the SV40 intron from the
      inverted repeat was critical for the transcribed RNA to function in RNAi.

PMID- 11587536
TI  - Insulin-like growth factor type 1 upregulates uncoupling protein 3.
AB  - In this study the expression of uncoupling protein 3 (UCP3) and its regulation by
      insulin-like growth factor 1 (IGF-I) and insulin in human neuroblastoma SH-SY5Y
      cells were characterized. Reverse transcriptase-PCR, Western blot, and
      immunofluorescence analysis showed that SH-SY5Y cells express UCP3 natively. IGF
      I induced a time- and concentration-dependent induction of UCP3 protein reaching
      a twofold expression after 72 h with 10 nM IGF-I. Extremely high insulin
      concentrations (860 nM) and 10 nM trIGF-I, a truncated form of IGF-I with the
      same affinity for the IGF-I receptor as the full-length IGF-I, but with lower
      activity on the insulin receptor, also upregulated UCP3. We conclude that SH-SY5Y
      cells express UCP3 natively and that the expression is regulated by IGF-I via the
      IGF-I receptor.

PMID- 11587537
TI  - Mitochondrial lipid alterations during Fas- and radiation-induced apoptosis.
AB  - In the present study, we investigated the dynamic alterations in mitochondrial
      lipids occurring during Fas- and radiation-induced cell death. Cross-linking of
      CD-95 on Fas-sensitive Jurkat cells produced rapid increases in two species of
      mitochondrial phosphatidylglycerol. By 2.5 h, phosphatidylglycerol decreases
      below basal levels, concomitant with an increase in mitochondrial ceramide. In
      addition, between 1.5 and 3.0 h after anti-Fas crosslinking, there is a continued
      loss of mitochondrial cardiolipin. When gamma irradiation was used to induce
      apoptosis, similar lipid changes occurred, although with somewhat slower
      kinetics. Fas-resistant Jurkat cells exhibited phosphatidylglycerol as the
      dominant lipid species in their mitochondria. Following Fas ligation, there is a
      transient decrease in phosphatidylglycerol, but cardiolipin and ceramide remained
      unchanged. The high basal levels of PG in Fas-resistant cells and the increase in
      PG levels in Fas-sensitive cells undergoing apoptosis was determined to be due to
      increased PGP synthase activity. Thus, critical mitochondrial lipids could
      potentially serve as novel targets in regulating the apoptotic process.

PMID- 11587538
TI  - Inhibition of ceramide production reverses TNF-induced insulin resistance.
AB  - Ceramide has been implicated as a mediator of insulin resistance induced by tumor
      necrosis factor-alpha (TNF) in adipocytes. Adipocytes contain numerous caveolae,
      sphingolipid and cholesterol-enriched lipid microdomains, that are also enriched
      in insulin receptor (IR). Since caveolae may be important sites for crosstalk
      between tyrosine kinase and sphingolipid signaling pathways, we examined the role
      of increased caveolar pools of ceramide in regulating tyrosine phosphorylation of
      the IR and its main substrate, insulin receptor substrate-1 (IRS-1). Neither
      exogenous short-chain ceramide analogs nor pharmacologic increases in endogenous
      caveolar pools of ceramide inhibited insulin-induced tyrosine phosphorylation of
      the IR and IRS-1. However, inhibition of TNF-induced caveolar ceramide production
      reversed the decrease in IR tyrosine phosphorylation in response to TNF. These
      results suggest that TNF-independent increases in caveolar pools of ceramide are
      not sufficient to inhibit insulin signaling but that in conjunction with other
      TNF-dependent signals, caveolar pools of ceramide are a critical component for
      insulin resistance by TNF.

PMID- 11587539
TI  - Mutant of LolA, a lipoprotein-specific molecular chaperone of Escherichia coli,
      defective in the transfer of lipoproteins to LolB.
AB  - The outer membrane-specific lipoproteins of Escherichia coli are released from
      the inner membrane as a water-soluble complex with LolA and then transferred to
      the outer membrane receptor, LolB. LolA thus plays a critical role in the sorting
      and outer membrane localization of lipoproteins. To dissect the LolA function,
      the highly conserved residues were subjected to random mutagenesis, followed by
      selection for a growth defect. LolA(R43L), one of mutants thus constructed,
      possessed Leu in place of Arg at position 43 and caused accumulation of the
      LolA(R43L)-lipoprotein complex in the periplasm. LolA(R43L) was as active as wild
      type LolA as to the release of lipoproteins from spheroplasts. In marked
      contrast, the transfer of lipoproteins from LolA(R43L) to LolB was completely
      inhibited, indicating that Arg at position 43 of LolA is involved in the
      lipoprotein transfer reaction.

PMID- 11587540
TI  - How does a g993t mutation in the emerin gene cause Emery-Dreifuss muscular
      dystrophy?
AB  - X-linked Emery-Dreifuss muscular dystrophy is usually caused by absence of the
      nuclear membrane protein, emerin, due to nonsense mutations or deletions, but a
      few missense mutations also exist. A pathogenic g993t mutation causes a Q133H
      change in the nuclear targeting region of emerin, but it may also reduce emerin
      levels by affecting mRNA splicing. We have introduced the g993t mutation by in
      vitro mutagenesis and studied the effect of Q133H on nuclear targeting by
      transfection of COS-7 cells. No qualitative or quantitative differences in
      nuclear targeting were observed between normal and mutant emerin. Quantitative
      BIAcore analysis showed no significant change in lamin A binding to emerin when
      the mutation was present. We conclude that Q133 is not essential for nuclear
      targeting of emerin or its interaction with lamin A. Reduced emerin levels due to
      altered splicing or defective interaction with an unidentified binding partner
      remain possible pathogenic mechanisms.

PMID- 11587541
TI  - Hydrogen peroxide activates Na(+)-dependent Ca(2+) influx in coronary endothelial
      cells.
AB  - The purpose of the present study was to examine the effect of short duration
      H(2)O(2) exposure on coronary artery endothelial cell [Ca(2+)](i) regulation.
      Freshly dispersed cells from porcine coronary artery were exposed to H(2)O(2)
      (300 micromol/L) for 3 min while monitoring [Ca(2+)](i) using fura-2
      microfluorometry. H(2)O(2) increased [Ca(2+)](i) from 0.86 +/- 0.03 to 2.19 +/-
      0.41 ratio units at 3 min of H(2)O(2) (P < 0.05). Intracellular Ca(2+) remained
      elevated 3 min following removal of H(2)O(2), yet H(2)O(2) had no effect on the
      subsequent [Ca(2+)](i) response to bradykinin (0.1 micromol/L). The H(2)O(2)
      induced [Ca(2+)](i) increase was completely abolished either by removal of
      extracellular Ca(2+) or lowering extracellular Na(+). Cells exposed to the Na(+)
      ionophore, monensin, showed an increase in [Ca(2+)](i) with a time course similar
      to that seen with H(2)O(2). Furthermore, H(2)O(2)-induced Ca(2+) influx was not
      attenuated by either Ni(2+) (300 micromol/L) or econazole (10 micromol/L),
      excluding Ca(2+) influx via the agonist-sensitive pathway. Thus, in coronary
      arterial endothelial cells, H(2)O(2) increases Ca(2+) influx in an extracellular
      Na(+)-dependent manner via an agonist-insensitive pathway.

PMID- 11587542
TI  - Opposite role of Ras in tumor necrosis factor-alpha-induced cell cycle
      regulation: competition for Raf kinase.
AB  - Ras, a well-known oncogene, induces cell cycle stimulation through the Raf/Erk
      pathway and leads to cellular transformation, accompanied by other oncogenes such
      as c-myc and viral oncogenic protein. Here we suggest the interfering role of Ras
      in tumor necrosis factor (TNF)-alpha-induced cell cycle regulation. In TSU-Pr1
      and T24 (oncogenic Ras cell lines), TNF-alpha suppresses cell cycle progression
      without induction of apoptosis, whereas AGS (wild-type Ras) is stimulated in its
      cell cycle by TNF-alpha coupled with activation of Erk. However, in TSU-Pr1 and
      T24, TNF-alpha leads to dephosphorylation of Erk1/2. Inhibition or activation of
      Ras can restore or convert TNF-alpha-induced cell cycle regulation in the cell
      lines containing the oncogenic Ras (TSU-Pr1 and T24) or AGS, respectively.
      Regulation of Erk also shows the coincidental pattern. We suggest the competition
      between the Ras pathway and TNF signaling for the binding to Raf, a common
      downstream target, as the cause of such reciprocal response, based on co
      immunoprecipitation (co-IP) with antibodies against Raf and Ras or cellular Flice
      inhibitory protein (c-FLIP), which have been recently identified upstream of Raf
      in death-ligand-induced cell cycle stimulation. Overexpression of Raf in TSU-Pr1,
      to reduce the competition, overcomes TNF-induced cell cycle arrest, also
      supporting our hypotheses.

PMID- 11587543
TI  - Gene structure and transcriptional regulation of human Gal beta1,4(3) GlcNAc
      alpha2,3-sialyltransferase VI (hST3Gal VI) gene in prostate cancer cell line.
AB  - We describe transcriptional regulation of the human Gal beta1,4(3) GlcNAc
      alpha2,3-sialyltransferase VI (hST3Gal VI) gene. The 5'-RACE results indicated
      that two mRNA forms differ only in the 5'-untranslated region (types 1 and 2).
      The genomic structure shows that the transcriptional regulation of type 1 and
      type 2 mRNA depends on the P1 and P2 promoters, respectively. Northern blots of
      RNA derived from various human tissues showed that the expression level of type 2
      mRNA is higher than that of type 1 in the prostate. To elucidate the molecular
      basis of hST3Gal VI gene expression, we isolated and functionally characterized
      the genomic region containing the P1 and P2 promoters of hST3Gal VI. The activity
      of the P2 promoter is much higher than that of the P1 promoter in the prostate
      adenocarcinoma cell line PC-3. The results suggested that the hST3Gal VI gene is
      expressed specifically by alternative promoter utilization and is regulated in a
      tissue-restricted fashion at the level of transcription.

PMID- 11587544
TI  - Local and systemic expression of insulin-like growth factor-I (IGF-I) mRNAs in
      rat after bone marrow ablation.
AB  - Local and systemic expression of insulin-like growth factor-I (IGF-I) during bone
      formation was studied using the rat bone marrow ablation model. The temporal
      expression pattern of IGF-I mRNA in rat femurs was examined. The IGF-I mRNA level
      was enhanced rapidly after ablation reaching a level threefold greater than basal
      by day 3 (P < 0.01) and declined to basal or below basal level by day 5.
      Histological analysis showed that IGF- I immunoreactivity was predominantly
      associated with the mesenchymal cells at the bone/connective tissue interface and
      osteoblastic cells at active sites of bone formation. Serum level of IGF-I
      increased 50 and 130%, respectively (P < 0.005), over the basal level at days 3
      and 6. We also investigated the systemic expression of IGF-I in liver and kidney.
      In contrast, hepatic IGF-I gene expression decreased 37 and 48%, respectively, at
      days 3 and 6 after marrow ablation (P < 0.001). Kidney IGF-I mRNA levels also
      fell 13 and 27%, respectively, at days 3 and 6 (P < 0.005). The present findings
      suggest that locally produced IGF-I during bone formation may not only serve as
      an autocrine/paracrine factor but also influence systemic expression of IGF-I in
      other organs.

PMID- 11587545
TI  - Bystander effects of nucleoside analogs phosphorylated in the cytosol or
      mitochondria.
AB  - The efficiency of nucleoside kinase suicide gene therapy for cancer is highly
      dependent on "bystander" cell killing, i.e., the transfer of cytotoxic
      phosphorylated nucleoside analogs to cells adjacent to those expressing the
      suicide enzyme. We have recently studied the possible use of mitochondrial
      nucleoside kinases as suicide genes. In the present study, we investigated if
      nucleoside analogs phosphorylated in the mitochondrial matrix cause bystander
      killing. We used deoxycytidine kinase-deficient Chinese hamster ovary cells
      reconstituted with deoxycytidine kinase targeted to either the cytosol or
      mitochondria matrix and determined the bystander cell killing when these cells
      were incubated with the nucleoside analogs 1-beta-D-arabinofuranosylcytosine and
      2',2'-difluorodeoxycytidine. A bystander effect occurred when nucleoside analogs
      were phosphorylated in the cytosol, but not when these compounds were
      phosphorylated in the mitochondria. These findings suggest that nucleoside
      kinases targeted to the mitochondrial matrix have limited use in suicide gene
      therapy when efficient bystander cell killing is required.

PMID- 11587547
TI  - Calcium influx, arachidonic acid,and control of endothelial cell proliferation.
AB  - Recent evidences suggest a role for arachidonic acid (AA) in the triggering of
      store-independent, ornon-capacitative, calcium entry in different cell types.
      Here, using patch clamp and fluorimetric single-cell calcium measurements, we
      provide evidence for AA-activated calcium influx in bovine aortic endothelial
      cells (BAEC). AA-activated calcium entry is independent from intracellular
      calcium stores depletion at low doses of the fatty acid (< 5 microM) and
      insensitive to a decrease of pH to 6.7. Single-channel analysis in inside-out
      configuration reveals the presence of a family of AA-activated calcium-permeable
      channels, with different conductances and reversal potentials. Treatment with AA
      or ETYA induces a proliferative effect, significantly affected by external EGTA
      application during the early period (up to 2h) of stimulation with the agonists.
      We conclude that low concentrations of arachidonic acid are able to evoke a store
      independent calcium influx, exerting a mitogenic role in BAECs.

PMID- 11587546
TI  - Vasoactive intestinal peptide (VIP) stimulates [Ca2+]i and cyclic AMPin CHO cells
      expressing Galpha16.
AB  - The stimulatory effect of vasoactive intestinal peptide (VIP) and analogues on
      [Ca2+]i has been investigated in chinese hamster ovary (CHO) cells stably
      transfected with the reporter gene aequorin, and expressing either the human
      VPAC1or VPAC2 receptor in absence or in presence of the Galpha16. In cells that
      were not transfected with Galpha16 and expressed a similar density of receptors,
      the VIP induced [Ca2+]i ncrease was higher in VPAC1 than in VPAC2 receptor
      expressing cells. In aequorin/Galpha16 cotransfected cells, the VIP-induced
      response was higher, reaching 70 to 80% of the maximal calcium response, obtained
      after digitonin treatment, in response to both VPAC1 and VPAC2 receptor
      stimulation. The results suggest that in hematopoietic cells, which express both
      VIP receptors and Galpha16, the signalling pathway of VIP could be mediated
      through both cyclic AMP and [Ca2+]i increase.

PMID- 11587548
TI  - Inositol 1,4,5-trisphosphate receptor isoforms show similar Ca2+ release
      kinetics.
AB  - The inositol 1,4,5-trisphosphate receptor (InsP3R) is an intracellular Ca2+
      release channel which upon activation initiates many cellular functions. Multiple
      InsP3R subtypes are expressed in most cell types but the physiological
      significance of this heterogeneity is poorly understood. This study has directly
      compared the functional properties of the three different InsP3R isoforms by
      analyzing their InsP3-induced Ca2+ release (IICR) properties in cell lines which
      predominantly express each isoform subtype. The InsP3-dependence of the amount or
      extent of IICR was InsP3R isoform-specific, with the type III isoform having the
      lowest affinity with respect to Ca2+ release. The transient kinetics of IICR,
      measured using stopped-flow spectrofluorimetry, however, were similar for all
      three InsP3R isoforms. At maximal InsP3 concentrations (20 microM) the rate
      constants where between 0.8 and 1.0 s(-1) for the fast phase and 0.25-0.45 s(-1)
      for the slow phase. The concentration of InsP3 required to induce half-maximal
      rates of Ca2+ release (EC50) were also similar for the three isoforms (0.2-0.4
      microM for the fast phase and 0.75-0.95 microM for the slow phase). These results
      indicate the InsP3R channel does not significantly differ functionally in terms
      of Ca2+ release rates between isoforms. The temporal and spatial features of
      intracellular Ca2+ signals are thus probably achieved through InsP3R isoform
      specific regulation or localization rather than their intrinsic Ca2+ efflux
      properties.

PMID- 11587549
TI  - P2X and P2Y purinoreceptors mediate ATP-evoked calcium signalling in optic nerve
      glia in situ.
AB  - It is known that ATP acts as an extracellular messenger mediating Ca2+ signalling
      in glial cells. Here, the mechanisms involved in the ATP-evoked increase in glial
      [Ca2+]i were studied in situ, in the acutely isolated rat optic nerve. ATP and
      agonists for P2X (a,b-metATP) and P2Y (2MeSATP) purinoreceptors triggered raised
      glial [Ca2+]i, and there was no significant difference between cells identified
      morphologically as astrocytes and oligodendrocytes. Dose-response curves
      indicated that P2Y receptors were activated at nanomolar concentrations, whereas
      P2X purinoreceptors were only activated above 10 microM. The rank order of
      potency for several agonists indicated optic nerve glia expressed heterogeneous
      purinoreceptors, with P2Y1< or = P2Y2/4< or = P2X. The ATP evoked increase in
      [Ca2+]i was reversibly blocked by the P2X/Y purinoreceptor antagonist suramin
      (100 microM) and markedly reduced by thapsigargin (10 microM), which blocks IP3
      dependent release of Ca2+ from intracellular stores. Removal of extracellular
      Ca2+ reduced the ATP evoked increase in [Ca2+]i and completely blocked its
      recovery, indicating that refilling of intracellular stores was ultimately
      dependent on Ca2+ influx from the extracellular milieu. The results implicate ATP
      as an important signal in CNS white matter astrocytes and oligodendrocytes in
      situ, and indicate that metabotropic P2Y purinoreceptors mobilize intracellular
      Ca2+ at physiological concentrations of ATP, whereas ionotropic P2X
      purinoreceptors induce Ca2+ influx across the plasmalemma only at high
      concentrations of ATP, such as occur following CNS injury.

PMID- 11587550
TI  - Cytosolic-free calcium in smooth-muscle and endothelial cells in an intact
      arterial wall from rat mesenteric artery in vitro.
AB  - The regulation of cytosolic-free calcium concentration of smooth-muscle and
      endothelial cells was mainly studied on cultured cells where the cross talk
      between these two coupled cell types is lost. In the present study, the cytosolic
      free calcium concentration in the endothelial and the smooth-muscle cells was
      examined in an intact arterial wall in vitro. Strips of the main branch of rat
      mesenteric artery were used. Cytosolic-free calcium concentration [Ca2+]i was
      estimated by determining the fluorescence ratio of the two calcium probes, Fluo-4
      and Fura red. The emitted fluorescence of both probes was measured with a
      confocal microscope. We showed that potassium and phenylephrine, which increase
      the cytosolic -free calcium concentration of the smooth-muscle cells, also
      indirectly influence the calcium concentration in the endothelial cells. By
      simultaneously determining [Ca2+]i in the endothelial and the smooth-muscle cells
      of an arterial strip, we observed that when calcium increases in the endothelial
      cells in response to acetylcholine, it slightly decreases in the smooth-muscle
      cells. We conclude that the regulation of [Ca2+]i in the arterial endothelial
      cell, depends according to the stimuli either upon the endothelial cells
      themselves, or upon the coupled smooth-muscle cells.

PMID- 11587551
TI  - Lack of effect of cADP-ribose and NAADP on the activity of skeletal muscle and
      heart ryanodine receptors.
AB  - The calcium release channels/ryanodine receptors (RyRs) are potential/putative
      targets of cADPR (cyclic ADP-ribose) action in many tissue systems. In striated
      muscles, where RyRs predominate, cADPR action on these channels is controversial.
      Here cADPR modulation of cardiac and skeletal muscle RyR channels was tested. We
      considered factors reported as necessary for cADPR action, such as the presence
      of calmodulin and/or FK binding proteins (FKBPs). We found: 1) The RyR channel
      isoforms were insensitive to cADPR (or its metabolite NAADP [nicotinic acid
      adenine dinucleotide phosphate]) under all conditions examined, as studied by:
      1a) single channel recordings in planar lipid bilayers; 1b) macroscopic behavior
      of the RyRs in sarcoplasmic reticulum (SR) microsomes (including crude microsome
      preparations likely to retain putative cADPR cofactors) at room temperature and
      at 37 degrees C (net energized Ca2+ uptake or passive Ca2+ leak); 2) [32P]cADPR
      did not bind significantly to SR microsomes; 3) cADPR did not affect FKBP
      association to SR membranes. We conclude that cADPR does not interact directly
      with RyRs or RyR-associated SR proteins. Our results under in vitro conditions
      suggest that c ADPR effects on Ca2+ signaling observed in vivo in mammalian
      striated muscle cells may reflect indirect modulation of RyRs or RyR-independent
      Ca2+ release systems.

PMID- 11587552
TI  - Epileptogenesis induces long-term alterations in intracellular calcium release
      and sequestration mechanisms in the hippocampal neuronal culture model of
      epilepsy.
AB  - Calcium and calcium-dependent processes have been hypothesized to be involved in
      the induction of epilepsy. It has been shown that epileptic neurons have altered
      calcium homeostatic mechanisms following epileptogenesis in the hippocampal
      neuronal culture (HNC) and pilocarpine models of epilepsy. To investigate the
      mechanisms causing these alterations in [Ca2+]i homeostatic processes following
      epileptogenesis, we utilized the HNC model of in vitro 'epilepsy' which produces
      spontaneous recurrent epileptiform discharges (SREDs). Using [Ca2+]i imaging,
      studies were initiated to evaluate the mechanisms mediating these changes in
      [Ca2+]i homeostasis. 'Epileptic' neurons required much longer to restore a
      glutamate induced [Ca2+]i load to baseline levels than control neurons.
      Inhibition of Ca2+ entry through voltage and receptor gated Ca2+ channels and
      stretch activated Ca2+ channels had no effect on the prolonged glutamate induced
      increase in [Ca2+]i in epileptic neurons. Employing thapsigargin, an inhibitor of
      the sarco/endoplasmic reticulum calcium ATPase (SERCA), it was shown that
      thapsigargin inhibited sequestration of [Ca2+]i by SERCA was significantly
      decreased in 'epileptic' neurons. Using Ca2+ induced Ca2+ release (CICR) cell
      permeable inhibitors for the ryanodine receptor (dantrolene) and the IP3 receptor
      (2-amino-ethoxydiphenylborate, 2APB) mediated CICR, we demonstrated that CICR was
      significantly augmented in the 'epileptic' neurons, and determined that the IP3
      receptor mediated CICR was the major release mechanism altered in
      epileptogenesis. These data indicate that both inhibition of SERCA and
      augmentation of CICR activity contribute to the alterations accounting for the
      impaired calcium homeostatic processes observed in 'epileptic' neurons. The
      results suggest that persistent changes in [Ca2+]i levels following
      epileptogenesis may contribute to the long-term plasticity changes manifested in
      epilepsy and that understanding the basic mechanisms mediating these changes may
      provide an insight into the development of novel therapeutic approaches to treat
      epilepsy and prevent or reverse epileptogenesis.

PMID- 11587553
TI  - Hypothalamic hormones and cancer.
AB  - The use of peptide analogs for the therapy of various cancers is reviewed.
      Inhibition of the pituitary-gonadal axis forms the basis for oncological
      applications of luteinizing hormone-releasing hormone (LH-RH) agonists and
      antagonists, but direct effects on tumors may also play a role. Analogs of
      somatostatin are likewise used for treatment of various tumors. Radiolabeled
      somatostatin analogs have been successfully applied for the localization of
      tumors expressing somatostatin receptors. Studies on the role of tumoral LH-RH,
      growth hormone-releasing hormone (GH-RH), and bombesin/GRP and their receptors in
      the proliferation of various tumors are summarized, but the complete elucidation
      of all the mechanisms involved will require much additional work. Human tumors
      producing hypothalamic hormones are also discussed. Treatment of many cancers
      remains a major challenge, but new therapeutic modalities are being developed
      based on antagonists of GH-RH and bombesin, which inhibit growth factors or their
      receptors. Other approaches consist of the use of cytotoxic analogs of LH-RH,
      bombesin, and somatostatin, which can be targeted to receptors for these peptides
      in various cancers and their metastases. These new classes of peptide analogs
      should lead to a more effective treatment for various cancers.

PMID- 11587554
TI  - New evidence for estrogen receptors in gonadotropin-releasing hormone neurons.
AB  - Estrogen exerts a critical regulatory influence upon the biosynthetic and
      secretory activity of the gonadotropin-releasing hormone (GnRH) neurons. It seems
      likely that estrogen regulates the behavior of the GnRH neuron through multiple
      transsynaptic, neuronal-glial, and direct membrane modes of action. Advances in
      our understanding of these mechanisms over the last 3 years are highlighted. In
      addition, very recent studies have begun to provide evidence for the expression
      of estrogen receptors (ERs) in GnRH neurons in the rodent. Although not yet
      firmly established, the current consensus supports the hypothesis that GnRH
      neurons express ERbeta. Evidence exists for ERbeta mRNA expression by GnRH
      neurons throughout development and ERbeta immunoreactivity has now also been
      detected in these cells. Murine GnRH neurons have further been shown to express
      estrogen receptor-related receptor-alpha, an orphan receptor thought to
      constitutively activate estrogen response elements. Together, these findings
      provide a cornerstone for the reassessment of the role of ERs and related
      receptors in the direct genomic and potential nontranscriptional actions of
      estrogen upon the GnRH neuron.

PMID- 11587555
TI  - Neuroendocrine tumor markers.
AB  - Tumor markers used in the diagnosis and follow-up of patients with neuroendocrine
      tumors are in most instances not specific for a given tumor and circulate under
      normal conditions in the serum, making their use as an early diagnostic tool
      difficult (low sensitivity). By combining hormone measurements with tissue
      responsiveness, demonstrations of inappropriate secretions of PTH, insulin, and
      gastrin during hypercalcemia, hypoglycemia, and hyperacidity, respectively,
      become highly sensitive and specific diagnostic tests. The application of
      polyclonal antibodies in RIAs of hormones, such as ACTH, insulin, and gastrin,
      increase the diagnostic level of hormone measurements in patients with
      neuroendocrine tumors. Other markers, such as chromogranin A, neuron-specific
      enolase, and alpha-subunit, as well as peptide receptor visualization, are of
      increasing importance in the diagnosis and follow-up of neuroendocrine and non
      neuroendocrine tumors.

PMID- 11587556
TI  - Transforming growth factor-beta regulation of estradiol-induced prolactinomas.
AB  - Prolactin-secreting adenomas (prolactinomas) are the most prevalent form of
      pituitary tumors in humans, and increased tumor growth under estrogenic influence
      in female patients is often of clinical concern. Extensive experimental work has
      uncovered the roles of estrogen receptors and various growth-regulatory peptides
      in estradiol action on lactotropes. However, it is only recently that we are
      beginning to gain insight into how these growth factors interact to regulate
      estradiol action on lactotrope cell proliferation. Recent studies have identified
      the regulatory role of TGF-beta-related peptides in estradiol action on
      lactotropes. Additionally, these studies determined that TGF-beta and FGF
      interact to facilitate the communication between lactotropes and
      folliculostellate cells that is necessary for the mitogenic action of estradiol.
      This review addresses the role of estradiol in prolactinoma formation and
      summarizes data that support a novel concept: Alterations in the expression and
      action of TGF-beta isoforms are crucial steps in estradiol-induced tumorigenesis.

PMID- 11587557
TI  - Heat stress-activated, calcium-dependent nitric oxide synthase in sponges.
AB  - The presence of Ca(2+)-dependent, heat-stress-activated nitric oxide synthase
      (NOS) activity in peculiarly shaped, fusiform, and dendritic sponge cells is
      described for the first time. The NOS activity was evidenced evaluating the
      conversion of radioactive citrulline from [(14)C]arginine in intact cells from
      two different species that are phylogenetically unrelated in the class of
      Demospongiae: Axinella polypoides and Petrosia ficiformis. The production of
      nitrogen monoxide (NO) was confirmed by electron paramagnetic resonance analysis,
      and the histochemistry technique of NADPH diaphorase showed a specific
      localization of NOS activity in a particular network of dendritic cells in the
      sponge parenchyma. Sponges are the most primitive metazoan group; their evolution
      dates back 600 million years. The presence of environmental stress-activated NOS
      activity in these organisms may prove to be the most ancient NO-dependent
      signaling network in the animal kingdom.

PMID- 11587558
TI  - Acetaminophen-induced hepatotoxicity in mice lacking inducible nitric oxide
      synthase activity.
AB  - We recently reported that nitrotyrosine and acetaminophen (APAP)-cysteine protein
      adducts colocalize in the hepatic centrilobular cells following a toxic dose of
      APAP to mice. Whereas APAP-adducts are formed by reaction of the metabolite N
      acetyl-p-benzoquinone imine with cysteine, nitrotyrosine residues are formed by
      reaction of tyrosine with peroxynitrite. Peroxynitrite is formed from nitric
      oxide (NO) and superoxide. This manuscript examines APAP (300 mg/kg)
      hepatotoxicity in mice lacking inducible nitric oxide synthase activity (NOS2
      null or knockout mice; C57BL/6-Nos2(tm1Lau)) and in the wildtype mice. In a time
      course the ALT levels in the exposed NOS2 null mice were approximately 50% of the
      wildtype mice; however, histological examination of liver sections indicated
      similar levels of centrilobular hepatic necrosis in both wild-type and NOS2 null
      mice. Serum nitrate plus nitrite levels (NO synthesis) were identical in saline
      treated NOS2 null and wild-type mice (53 +/- 2 microM). APAP increased NO
      synthesis in wild-type mice only. The increases paralleled the increases in ALT
      levels with peak levels of serum nitrate plus nitrite at 6 h (168 +/- 27 microM).
      In wild-type mice hepatic tyrosine nitration was greatly increased relative to
      saline treated controls. Tyrosine nitration increased in NOS2 null mice also, but
      the increase was much less. APAP increased hepatic malonaldehyde levels (lipid
      peroxidation) in NOS2 null mice only. The results suggest the presence of
      multiple pathways to APAP-mediated hepatic necrosis, one via nitrotyrosine, as in
      the wild-type mice, and another that is not dependent upon inducible nitric oxide
      synthase activity, but which may involve increased superoxide.

PMID- 11587559
TI  - Titration of low K(d) binding sites: binding of arginine analogs to nitric oxide
      synthases.
AB  - Spectrophotometrically monitored ligand titration is an important method for the
      determination of equilibrium dissociation constants (K(d)) from nitric oxide
      synthases (NOS). Low K(d) sites such as the tetrahydrobiopterin and arginine
      binding sites present difficulties in that experiments often require enzyme
      concentrations of the same magnitude as the K(d). An analytical method based on
      computer simulation is described that allows the estimation of K(d) values
      without an independent means of monitoring free ligand or without an accurate
      prior determination of the number of binding sites. The K(d) for arginine is
      approximately 0.5 microM for the tetrahydrobiopterin replete neuronal and
      inducible isoforms (nNOS and iNOS), while the endothelial isoform has a slightly
      higher K(d) (1.5 microM). N-OH-arginine (an intermediate) binds to nNOS with a
      K(d) of around 0.2 microM, while the inhibitors N-methyl-arginine and N-nitro
      arginine bind more tightly; our best K(d) estimates are 100 nM or lower.

PMID- 11587560
TI  - Shear stress-induced nitric oxide release triggers the liver regeneration
      cascade.
AB  - The trigger of the liver regeneration cascade is currently unknown and has been
      the subject of debate. We hypothesize that, following 2/3 partial hepatectomy
      (PHX), an increase in the blood flow-to-liver mass ratio results in shear stress
      induced nitric oxide (NO) release, which triggers the liver regeneration cascade.
      Portal venous pressure (PVP), reflecting shear stress in the liver, increased to
      the same extent following PHX and selective portal vein branch ligation (PVL), a
      hemodynamic model of PHX, suggesting similar amounts of shear stress in both
      models. Two indices of the initiation of the liver regeneration cascade were
      used: proliferative factor (PF) activity in blood 4 h after PHX or PVL and
      hepatic c-fos mRNA expression 15 min. after PHX or PVL. PF activity and c-fos
      mRNA expression were increased to similar extents after PHX and PVL, suggesting a
      similar stimulus in both models. PF activity and c-fos mRNA expression were
      inhibited by administration of the nitric oxide synthase antagonist, l-NAME, and
      the NO donor, SIN-1, reversed the inhibition in both models. These results
      provide support for the hypothesis that a hemodynamic change results in increased
      shear stress in the liver causing generation of NO, which then triggers the liver
      regeneration cascade.

PMID- 11587561
TI  - Nitric oxide is generated in smooth muscle layer by neurokinin A and counteracts
      constriction in guinea pig airway.
AB  - It has been reported that several bronchoconstrictors generate nitric oxide (NO),
      counteracting bronchoconstriction, and removal of bronchial epithelia reduces NO
      production. However, it has not been elucidated whether neurokinin A (NKA), a
      potent bronchoconstrictor liberated from nerve terminals, generates NO. Specific
      questions in this study were (1) does NKA also generate NO, (2) does NO
      counteract NKA-induced bronchoconstriction, and (3) does the NO generation
      require bronchial epithelial cells? In an in vivo study exogenous as well as
      endogenous (capsaicin-induced) NKA increased airway opening pressure (P(ao)) and
      the exhaled NO level, and both were inhibited by an antagonist selective for
      NK(2) receptor (a receptor for NKA), SR48968. The exhaled NO level became
      negligible with an inhibitor of NO synthase (NOS) type 1-3 (N(G)-nitro-L-arginine
      methyl ester, L-NAME) with increased P(ao), but not with a NOS type 2 inhibitor.
      In an in vitro study, NKA increased the nitrite/nitrate level in superfused fluid
      of tracheal segments. Removing smooth muscle reduced nitrite/nitrate in the fluid
      to negligible levels, while the level was unchanged with removal of the
      epithelia. Pretreatment with l-NAME enhanced the tension of epithelia-removed
      tracheal segments. These findings indicate that (1) NKA generates NO, (2) NO
      counteracts NKA-induced bronchoconstriction, and (3) NKA activates NOS in the
      muscle layer, independently of bronchial epithelia.

PMID- 11587562
TI  - A fluorescence-based method for measuring nitric oxide in extracts of skeletal
      muscle.
AB  - We describe here a fluorescence assay for nitric oxide synthase activity in
      skeletal muscle based on a new indicator, 4,5-diaminofluorescein (DAF-2). The
      rapid and irreversible binding of DAF-2 to oxidized NO allows real-time
      measurement of NO production. The method is safer and more convenient than the
      usual citrulline radioassay and can be used with crude muscle extracts. Rabbit
      fast tibialis anterior (TA) muscle had a nitric oxide synthase (NOS) activity of
      44.3 +/- 3.5 pmol/min/mg muscle. Addition of NOS blocker N(G)-allyl-L-arginine
      reduced this activity by 43%. Slow soleus muscle displayed NOS activity of 7.3 +/
      2.5 pmol/min/mg muscle, 16% that of the TA muscle. Continuous stimulation of TA
      muscle at 10 Hz for 3 weeks reduced NOS activity by 47% to an intermediate value
      consistent with the associated conversion of the muscle phenotype from fast to
      slow.

PMID- 11587563
TI  - Nitric oxide- and oxygen-derived free radical generation from control and
      lipopolysaccharide-treated rat polymorphonuclear leukocyte.
AB  - Previous studies from this lab have shown NO-mediated modulation of free radical
      generation from polymorphonuclear leukocytes (PMNs), following hypoxic
      reoxygenation as well as in the normoxic cells. The present study is an attempt
      to investigate further the regulation of NO and free radical generation in the
      lipopolysaccharide (LPS)-treated PMNs. PMNs were isolated from the rat blood and
      peritoneal cavity, 4 h after LPS (1 mg/kg, i.p.) treatment. Nitric oxide synthase
      (NOS) activity and nitrite content were increased in the peripheral and
      peritoneal PMNs following LPS treatment. An increase in the apparent V(max) for l
      arginine uptake was also observed in the LPS-treated peripheral PMNs, while
      peritoneal PMNs exhibited increase in both apparent V(max) and affinity for l
      arginine. Synthesis of nitrite did not augment after increasing the availability
      of substrate to control PMNs, however, peripheral and peritoneal PMNs from LPS
      treated rats utilized l-arginine more efficiently for nitrite synthesis. NOS
      activity, l-arginine uptake, and its utilization were maximal in the peritoneal
      PMNs. Arachidonic acid (AA, 1 x 10(-6) M)-induced free radical generation from
      PMNs was also enhanced significantly after LPS treatment. Preincubation of PMNs
      with nitrite elevated the free radical generation and myeloperoxidase (MPO)
      release. MPO and antioxidant enzyme activity in the PMNs was significantly
      augmented after LPS treatment. NOS inhibitors, aminoguanidine and 7
      nitroindazole, inhibited arachidonic acid-induced free radical generation from
      LPS treated PMNs. The results obtained thus indicate that augmentation of free
      radical generation from rat PMNs following LPS treatment appears to be regulated
      by NO and MPO.

PMID- 11587564
TI  - Role of endogenous nitric oxide generation in the regulation of vascular tone and
      reactivity in small vessels as investigated in transgenic mice using synchrotron
      radiation microangiography.
AB  - Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a central role
      in regulation of vascular tone and reactivity. The purpose of this study is to
      clarify the basal tone and microvascular reactivity in eNOS-overexpressing
      transgenic (Tg) mice in vivo with a microangiography system using monochromatic
      synchrotron radiation (SR). The mouse femoral artery was cannulated, nonionic
      contrast media was injected, and microangiography was performed in hindlimbs of
      mice. Serial images of the small blood vessels (diameter <200 microm) were
      recorded by the SR microangiography system. At basal conditions, the diameter of
      tibial arteries in eNOS-Tg mice was larger than that of wild-type mice (179 +/- 8
      versus 132 +/- 8 microm; P < 0.01). l-NAME treatment decreased the vessel
      diameter and canceled the difference in vessel diameters between two genotypes.
      Acetylcholine- and sodium nitroprusside-induced relaxations of small vessels were
      significantly reduced in Tg mice compared with wild-type mice (35.0 +/- 9.4
      versus 61.6 +/- 6.7%, 85.0 +/- 10.2 versus 97.3 +/- 6.7% of the maximum
      relaxation, respectively). Our data provide the evidence that overproduced NO
      from endothelium reduces vascular tone and plays a pivotal role in regulation of
      vascular tone in small vessels. Furthermore, the reduced NO-mediated relaxation
      in small vessels of eNOS-Tg mice is demonstrated for the first time in vivo. SR
      microangiography allows us to evaluate the reactivity in small-sized vessels and
      appears to be a powerful tool for assessing the microvascular circulation in
      vivo.

PMID- 11587566
TI  - Minimal reaction sets for Escherichia coli metabolism under different growth
      requirements and uptake environments.
AB  - A computational procedure for identifying the minimal set of metabolic reactions
      capable of supporting various growth rates on different substrates is introduced
      and applied to a flux balance model of the Escherichia coli metabolic network.
      This task is posed mathematically as a generalized network optimization problem.
      The minimal reaction sets capable of supporting specified growth rates are
      determined for two different uptake conditions: (i) limiting the uptake of
      organic material to a single organic component (e.g., glucose or acetate) and
      (ii) allowing the importation of any metabolite with available cellular transport
      reactions. We find that minimal reaction network sets are highly dependent on the
      uptake environment and the growth requirements imposed on the network.
      Specifically, we predict that the E. coli network, as described by the flux
      balance model, requires 224 metabolic reactions to support growth on a glucose
      only medium and 229 for an acetate-only medium, while only 122 reactions enable
      growth on a specially engineered growth medium.

PMID- 11587565
TI  - Antioxidant enzymes suppress nitric oxide production through the inhibition of NF
      kappa B activation: role of H(2)O(2) and nitric oxide in inducible nitric oxide
      synthase expression in macrophages.
AB  - Reactive molecules O(-)(2), H(2)O(2), and nitrogen monoxide (NO) are produced
      from macrophages following exposure to lipopolysaccharide (LPS) and involved in
      cellular signaling for gene expression. Experiments were carried out to determine
      whether these molecules regulate inducible nitric oxide synthase (iNOS) gene
      expression in RAW264.7 macrophages exposed to LPS. NO production was inhibited by
      the antioxidative enzymes catalase, horseradish peroxidase, and myeloperoxidase
      but not by superoxide dismutase (SOD). In contrast, the NO-producing activity of
      LPS-stimulated RAW264.7 cells was enhanced by the NO scavengers hemoglobin (Hb)
      and myoglobin. The antioxidant enzymes decreased levels of iNOS mRNA and protein
      in LPS-stimulated RAW264.7 cells, whereas the NOS inhibitor N(G)-monomethyl-L
      arginine as well as Hb increased the level of iNOS protein but not mRNA,
      indicating that NO inhibits iNOS protein expression. NF-kappa B was activated in
      LPS-stimulated RAW264.7 cells and the activation was significantly inhibited by
      antioxidant enzymes, but not by Hb. Similar results were obtained using LPS
      stimulated rodent peritoneal macrophages. Extracellular O(-)(2) generation by LPS
      stimulated macrophages was suppressed by SOD, but not by antioxidative enzymes,
      while accumulation of intracellular reactive oxygen species was inhibited by
      antioxidative enzymes, but not by SOD. Exogenous H(2)O(2) induced NF-kappa B
      activation in macrophages, which was inhibited by catalase and pyrroline
      dithiocarbamate (PDTC). H(2)O(2) enhanced iNOS expression and NO production in
      peritoneal macrophages when added with interferon-gamma, and the effect of
      H(2)O(2) was inhibited by catalase and PDTC. These findings suggest that H(2)O(2)
      production from LPS-stimulated macrophages participates in the upregulation of
      iNOS expression via NF-kappa B activation and that NO is a negative feedback
      inhibitor of iNOS protein expression.

PMID- 11587567
TI  - Novel hemoglobins to enhance microaerobic growth and substrate utilization in
      Escherichia coli.
AB  - Limited oxygen availability is a prevalent problem in microbial biotechnology.
      Recombinant Escherichia coli expressing the hemoglobin from Vitreoscilla (VHb) or
      the flavohemoglobin from Ralstonia eutropha (formerly Alcaligenes eutrophus)
      (FHP) demonstrate significantly increased cell growth and productivity under
      microaerobic conditions. We identify novel bacterial hemoglobin-like proteins and
      examine if these novel bacterial hemoglobins can elicit positive effects similar
      to VHb and FHP and if these hemoglobins alleviate oxygen limitation under
      microaerobic conditions when expressed in E. coli. Several finished and
      unfinished bacterial genomes were screened using R. eutropha FHP as a query
      sequence for genes (hmp) encoding hemoglobin-like proteins. Novel hmp genes were
      identified in Pseudomonas aeruginosa, Salmonella typhi, Klebsiella pneumoniae,
      Deinococcus radiodurans, and Campylobacter jejuni. Previously characterized hmp
      genes from E. coli and Bacillus subtilis and the novel hmp genes from P.
      aeruginosa, S. typhi, C. jejuni, K. pneumoniae, and D. radiodurans were PCR
      amplified and introduced into a plasmid for expression in E. coli. Biochemically
      active hemoproteins were expressed in all constructs, as judged by the ability to
      abduct carbon monoxide. Growth behavior and byproduct formation of E. coli K-12
      MG1655 cells expressing various hemoglobins were analyzed in microaerobic fed
      batch cultivations and compared to plasmid-bearing control and to E. coli cells
      expressing VHb. The clones expressing hemoglobins from E. coli, D. radiodurans,
      P.aeruginosa, and S. typhi reached approximately 10%, 27%, 23%, and 36% higher
      final optical density values, respectively, relative to the plasmid bearing E.
      coli control (A(600) 5.5). E. coli cells expressing hemoproteins from P.
      aeruginosa, S. typhi, and D. radiodurans grew to similar final cell densities as
      did the strain expressing VHb (A(600) 7.5), although none of the novel constructs
      was able to outgrow the VHb-expressing E. coli strain. Additionally, increased
      yield of biomass on glucose was measured for all recombinant strains, and an
      approximately 2-fold yield enhancement was obtained with D. radiodurans
      hemoprotein-expressing E. coli relative to the E. coli control carrying the
      parental plasmid without any hemoglobin gene.

PMID- 11587568
TI  - Production and molecular characterization of clinical phase i anti-melanoma mouse
      IgG3 monoclonal antibody R24.
AB  - R24 is a mouse IgG3 monoclonal antibody (mab) that reacts with the ganglioside
      GD3 expressed by cells of neuroectodermal origin. The anti-tumor activity of R24
      has been demonstrated in initial phase I and pilot trials in patients suffering
      from metastatic melanoma. The purpose of this study was to investigate the
      biotechnological production and particularly the glycosylation of this clinically
      important antibody. Growth, metabolism, and IgG production of R24 secreting
      hybridoma cells were analyzed on 1 L bioreactor bench scale using repeated-batch
      mode. The amount of 57 mg of pure mab was obtained from 1.6 L crude supernatant
      by protein A chromatography. Western blot binding assays with sugar-specific
      lectins revealed glycosylation of the heavy chains, whereas no carbohydrates were
      detectable on the light chains. Because glycosylation is essential for antibody
      effector functions in vivo (such as complement fixation or binding to macrophage
      Fc receptors), mab R24 was subjected to both enzymatic deglycosylation using
      PNGase F and chemical deglycosylation by hydrazinolysis. Released glycans were
      structurally characterized by high pH anion exchange chromatography with pulsed
      amperometric detection (HPAEC-PAD), matrix assisted laser desorption ionization
      time-of-flight (MALDI-TOF), and electrospray ionization quadrupole time-of-flight
      (ESI-QTOF) mass spectrometry. Six major biantennary chains of the complex
      glycosylation phenotype were found with variations in galactosylation and core
      fucosylation. The predominant N-linked structure, indicating the high degree of
      agalactosyl glycoforms, was the agalacto biantennary chain with a relative
      percentage of 57% (51% core-fucosylated, 6% nonfucosylated). The second most
      abundant oligosaccharide was the monogalacto biantennary chain amounting to 30%
      (26% core- and 4% nonfucosylated). The antibody contained 0.46 microg sialic acid
      per mg protein, which splits into 0.243 microg Neu5Gc and 0.217 microg Neu5Ac,
      corresponding to a Neu5Ac:Neu5Gc ratio of 1:1.06. Furthermore, the antigen
      specificity of R24 was determined by immunodetection of GD3 on thin-layer
      chromatograms, and real time GD3-antibody binding interactions were measured with
      an optical biosensor (BIAcore). From the structural data obtained in this study
      it is concluded that glycosylation of the antibody may be important in the
      clinical outcome of targeted anti-cancer immunotherapy.

PMID- 11587569
TI  - Production of a sialylated N-linked glycoprotein in insect cells.
AB  - Under High Aspect Ratio Vessel (HARV) bioreactor culture conditions designed to
      simulate the microgravity of orbital space flight, insect tissue culture cells
      infected with a baculovirus expression vector produced a human glycoprotein with
      tri- and tetra-antennary complex N-linked oligosaccharides containing terminal
      sialic acid residues. The oligosaccharide structures were similar to those
      produced in human placental cells. Insect cells cultured in T-flasks only
      performed incomplete oligosaccharide processing. The mechanism of HARV-mediated
      changes in the eukaryotic N-linked glycosylation pathway was investigated and
      could be mimicked under T-flask growth conditions with the addition of N
      acetylmannosamine to the culture medium. The significance of these investigations
      is discussed with respect to the production of recombinant therapeutic
      glycoproteins, insect physiology, and orbital space flight.

PMID- 11587570
TI  - New miniaturized hollow-fiber bioreactor for in vivo like cell culture, cell
      expansion, and production of cell-derived products.
AB  - We have developed a miniaturized hollow-fiber bioreactor system for mammalian
      cell culture with a volume of 1 mL. Cell and medium compartments of the
      bioreactor are separated by a semipermeable membrane, and oxygenation of the cell
      compartment is accomplished using an oxygenation membrane. As a result of the
      geometry of the transparent housing, cells can be observed by microscopy during
      culture. The leukemic cell lines CCRF-CEM, HL-60, and REH were cultivated up to
      densities of 3.5 x 10(7)/mL without medium change or manipulation of the cells.
      As shown using CCRF-CEM cells, growth in the bioreactor was strongly influenced
      and could be controlled by the medium flow rate. As a consequence, consumption of
      glucose and generation of lactate varied with flow rate. Depending on the
      molecular size cutoff of the membranes used, added growth factors such as GM-CSF,
      as well as factors secreted from the cells, are retained in the cell compartment
      for up to 1 week. This new miniaturized hollow-fiber bioreactor offers advantages
      in tissue engineering by continuous nutrient supply for cells in high density,
      retention of added or autocrine produced factors, and undisturbed long-term
      culture in a closed system.

PMID- 11587571
TI  - Improvement in enzyme productivities from mold cultivations using the liquid
      phase oxygen supply strategy.
AB  - Cultivations of Aspergillus niger cells in which oxygen was provided through the
      liquid-phase oxygen supply strategy (which involves the need-based decomposition
      of H2O2 pulses to yield the necessary oxygen) were studied. Concentrations of
      H2O2 in the range of 1 to 5 mM were found to be suitable for use in cultivations.
      The growth rate constant of 0.17 h(-1) obtained in the H2O2-based cultivation,
      was comparable to that obtained in the cultivation with aeration; however, the
      maximum cell concentration in the H2O2-based cultivation was 124% of that
      obtained in cultivation with aeration. Maximum concentrations of catalase,
      protease and glucose oxidase obtained in the H2O2-based cultivation, were 240%,
      172%, and 124% respectively, of those obtained in the cultivation with aeration.
      Further, the specific enzyme levels (units per gram cell) of catalase and
      protease obtained in the H2O2-based cultivation were 172% and 156% of those
      obtained in the cultivation with aeration, whereas, the specific glucose oxidase
      levels were comparable. In addition, the oxygen profiles inside the pellets ofA.
      niger during both the modes of oxygen supply were described using mathematical
      models. Studies to elucidate the mechanism of oxygen availability showed that the
      decomposition of the H2O2 supplied in the extracellular space occurred
      intracellularly, as well as extracellularly, to yield oxygen. Also, the proton
      motive force (PMF) was found to be involved in the process of oxygen availability
      from H2O2 to A. niger cells.

PMID- 11587572
TI  - Improvement of Panax notoginseng cell culture for production of ginseng saponin
      and polysaccharide by high density cultivation in pneumatically agitated
      bioreactors.
AB  - A Panax notoginseng cell culture was successfully scaled up from shake flask to
      1.0-L bubble column reactor and concentric-tube airlift reactor. High-density
      bioreactor batch cultivation was carried out using a modified MS medium. The
      maximum cell density in batch cultures reached 20.1, 21.0 and 24.1 g/L in the
      shake flask, bubble column and airlift reactors, respectively, and their
      corresponding biomass productivity was 950, 1140 and 1350 mg/(L x d) for each.
      The productivity of ginseng saponin was 70, 96 and 99 mg/(L x d) in the flask,
      bubble column and airlift reactors, respectively; and the polysaccharide
      productivity reached 104, 119 and 151 mg/(L x d) for each. Furthermore, a fed
      batch cultivation strategy was developed on the basis of specific oxygen uptake
      rate (SOUR), i.e., sucrose feeding before a sharp decrease of SOUR, and the
      highest cell density of 29.7 g/L was successfully achieved in the airlift
      bioreactor on day 17 with a very high biomass productivity of 1520 mg/(L x d).
      The concentrations of ginseng saponin and polysaccharide reached about 2.1 and
      3.0 g/L, respectively, and their productivity was 106 (saponin) and 158 mg/(L x
      d) (polysaccharide). This work successfully demonstrated the high-density
      bioreactor cultivation of P. notoginseng cells in pneumatically agitated
      bioreactors and the reproduction of the shake flask culture results in
      bioreactors. The cell density, biomass productivity, production titer and
      productivity of both ginseng saponin and polysaccharide obtained here were the
      highest that have been reported on a reactor scale for all the ginseng species.

PMID- 11587573
TI  - A microwave-powered sterilizable interface for aseptic access to bioreactors that
      are vulnerable to microbial contamination.
AB  - Novel methods and apparatus that employ the rapid heating characteristics of
      microwave irradiation to facilitate the aseptic transfer of nutrients, products,
      and other materials between microbially sensitive systems and the external
      environment are described. The microwave-sterilizable access port (MSAP) consists
      of a 600-W magnetron emitting at a frequency of 2.45 GHz, a sterilization chamber
      with inlet and outlet flow lines, and a specimen transfer interface. Energy is
      routed to the sterilization chamber via a coaxial transmission line where small
      quantities of water couple strongly with the incident radiation to produce a
      superheated vapor phase. The efficiency of energy transfer is enhanced through
      the use of microwave susceptors within the sterilization chamber. Mating surfaces
      are thermally sterilized through direct contact with the hot gas. Efficacy has
      been demonstrated using the thermophile Bacillus stearothermophilus.

PMID- 11587574
TI  - Impact of nitrate-mediated microbial control of souring in oil reservoirs on the
      extent of corrosion.
AB  - The effect of microbial control of souring on the extent of corrosion was studied
      in a model system consisting of pure cultures of the nitrate-reducing, sulfide
      oxidizing bacterium (NR-SOB) Thiomicrospira sp. strain CVO and the sulfate
      reducing bacterium (SRB) Desulfovibrio sp. strain Lac6, as well as in an SRB
      consortium enriched from produced water from a Canadian oil reservoir. The
      average corrosion rate induced by the SRB consortium (1.4 g x m(-2) x day(-1))
      was faster than that observed in the presence of strain Lac6 (0.2 g x m(-2) x
      day(-1)). Examination of the metallic coupons at the end of the tests indicated a
      uniform corrosion in both cases. Addition of CVO and 10 mM nitrate to a fully
      grown culture of Lac6 or the SRB consortium led to complete removal of sulfide
      from the system and a significant increase in the population of CVO, as
      determined by reverse sample genome probing. In the case of the SRB consortium
      addition of just nitrate (10 mM) had a similar effect. When grown in the absence
      of nitrate, the consortium was dominated by Desulfovibrio sp. strains Lac15 and
      Lac29, while growth in the presence of nitrate led to dominance of Desulfovibrio
      sp. strain Lac3. The addition of CVO and nitrate to the Lac6 culture or nitrate
      to the SRB consortium accelerated the average corrosion rate to 1.5 and 2.9 g x
      m(-2) x day(-1), respectively. Localized corrosion and the occurrence of pitting
      were apparent in both cases. Although the sulfide concentration (0.5-7 mM) had
      little effect on corrosion rates, a clear increase of the corrosion rate with
      increasing nitrate concentration was observed in experiments conducted with
      consortia enriched from produced water.

PMID- 11587575
TI  - Immobilized particles in gel matrix-type porous media. Homogeneous porous media
      model.
AB  - Diffusion in pure gels and gels with immobilized cells was analyzed. A model of
      diffusion assuming a homogeneous cell distribution in gel was improved by
      introducing a tortuosity value. By theoretical analysis and numerical modeling it
      was shown that the tortuosity of a gel with immobilized cells is the product of
      two factors: (1) tortuosity generated by the cells, Tc, and (2) tortuosity of the
      gel matrix, Tg, both variables being a function of cell volume fraction, phi(c).
      Total tortuosity is thus T(Sigma) = TcTg. On the basis of this approach, it was
      possible to analyze diffusivity data for gels with immobilized cells. It was
      shown that, in these systems, the diffusivity eta = D(e)/D(0) is a complex
      function of (1) diffusivity in the gel, eta(g), and (2) diffusivity in
      immobilized cells, eta(c). The developed model allowed for the description of the
      dependence of D(e)/D(0) on phi(c). Comparison with numerous published
      experimental data showed a good fit. Observed deviations might be explained by
      nonhomogeneous cell distributions inside the gel matrix.

PMID- 11587576
TI  - Activity studies of immobilized subtilisin on functionalized pure cellulose-based
      membranes.
AB  - The activity of immobilized subtilisin BPN' on pure cellulose-based membrane
      support was investigated using site-directed and random immobilization
      approaches. The catalytic activity of site-directed immobilized subtilisin on
      pure cellulose fiber-based materials was found to be 81% of that in homogeneous
      solution, while that of randomly immobilized subtilisin was 27%. Pure cellulose
      membrane supports provided large surface areas for high enzyme loading without
      diffusional limitations. The activity of immobilized subtilisin on pure cellulose
      support was more than twice that on a modified polyether sulfone (MPS) membrane,
      which was attributed to the higher hydrophilicity of cellulose. Immobilized
      subtilisin maintained its initial activity for 14 days at 4 degrees C and 7 days
      at 24 degrees C. The immobilized enzyme could resist higher temperature and
      operate over a wider range of pH without loss of activity. This study showed that
      pure cellulose fiber-based membranes are well suited for enzyme immobilization
      and biocatalysis.

PMID- 11587578
TI  - Production of a desulfurization biocatalyst by two-stage fermentation and its
      application for the treatment of model and diesel oils.
AB  - For the production of oil-desulfurizing biocatalyst, a two-stage fermentation
      strategy was adopted, in which the cell growth stage and desulfurization activity
      induction stage were separated. Sucrose was found to be the optimal carbon source
      for the growth of Gordonia nitida CYKS1. Magnesium sulfate was selected to be the
      sulfur source in the cell growth stage. The optimal ranges of sucrose and
      magnesium sulfate were 10-50 and 1-2.5 g x L(-1), respectively. Such a broad
      optimal concentration of sucrose made the fed-batch culture easy, while the
      sucrose concentration was maintained between 10-20 g x L(-1) in the actual
      operation. As a result, 92.6 g x L(-1) of cell mass was acquired by 120 h of fed
      batch culture. This cell mass was over three times higher than a previously
      reported result, though the strain used was different. The desulfurization
      activity of the harvested cells from the first stage culture was induced by batch
      cultivation with dibenzothiophene as the sole sulfur source. The optimal
      induction time was found to be about 4 h. The resting-cell biocatalyst made from
      the induced cells was applied for the deep desulfurization of a diesel oil. It
      was observed that the sulfur content of the diesel oil decreased from 250 mg
      sulfur x L-oil(-1) to as low as 61 mg-sulfur x L-oil(-1) in 20 h. It implied that
      the biocatalyst developed in this study had a good potential to be applied to a
      deep desulfurization process to produce ultra-low-sulfur fuel oils.

PMID- 11587577
TI  - High conversion in asymmetric hydrolysis during permeation through enzyme
      multilayered porous hollow-fiber membranes.
AB  - We describe a novel porous hollow-fiber support for immobilizing aminoacylase in
      multilayers. Epoxy-group-containing polymer chains were grafted onto a porous
      hollow-fiber membrane by radiation-induced graft polymerization of glycidyl
      methacrylate, and subsequently a diethylamino group as an anion-exchange group
      was introduced into the graft chain. Aminoacylase was adsorbed in multilayers by
      allowing the amioacylase buffer solution to permeate through the pores across the
      hollow fiber; the graft chains provided three-dimensional space for the enzymes
      because of their electrostatic repulsion. The adsorbed enzyme at a degree of
      multilayer binding of 15 was cross-linked with glutaraldehyde to prevent leakage.
      An acetyl-DL-methionine solution was allowed to permeate through the pores
      surrounded by the aminoacylase-immobilized graft chain. Production of L
      methionine was observed at a 4.1 mol/h per L of the fiber for a space velocity of
      200 h(-1), defined as the flow rate of the effluent penetrating the outside
      surface of the hollow fiber divided by the membrane volume including the lumen.

PMID- 11587579
TI  - Downstream processing of enzymatically produced geranyl glucoside.
AB  - Geraniol plays an important role in the fragrance and flavor industry. The
      corresponding glucoside has interesting properties as a "slow release" aroma
      compound. Therefore, the enzymatic production and downstream processing of
      geranyl glucoside were investigated. Geranyl glucoside was produced in a spray
      column reactor with an initial production rate of 0.58 mg x U(-1) x h(-1). A
      pretreated hydrophobic microfiltration membrane was used to prevent migration of
      the aqueous, enzyme-containing phase to the downstream process. No retention of
      the glucoside, which accumulated in the geraniol phase, was found. On the basis
      of examples from the literature, four downstream processes were tested on their
      viability for this system. Extraction with water and foaming were not suitable to
      recover geranyl glucoside from geraniol. In the first case, the glucoside
      selectivity for the geraniol phase was found to be high, which made extraction
      with water unsuccessful. In the second case it was possible to obtain a stable
      foam, but significant enrichment of the foam with glucoside did not occur.
      Adsorption on alumina and distillation under reduced pressure were applied
      successfully and tested in-line with the bioreactor. A maximum glucoside
      adsorption of 7.86 mg x g(-1) was achieved on alumina. After desorption and
      evaporation of the extractant the pure glucoside was obtained quantitatively. A
      pure product could not be obtained after distillation because a small amount of
      glucose was present in the permeate as well, which accumulated in the bottom
      fraction. It was shown that with this reactor system a production of 1 kg of
      geranyl glucoside in 2 days is possible using an initial amount of 50,000 units
      of enzyme.

PMID- 11587580
TI  - Sugar recovery and fermentability of hemicellulose hydrolysates from steam
      exploded softwoods containing bark.
AB  - The hemicellulose sugar recovery and ethanol production obtained from SO2
      catalyzed steam explosion of a mixed white fir (70%) and ponderosa pine (30%)
      feedstock containing bark (9% dry weight/dry weight) was assessed. More than 90%
      of the available hemicellulose sugars could be recovered in the hydrolysate
      obtained after steam explosion at 195 degrees C, 2.38 min, and 3.91% SO2, with
      59% of the original hemicellulose sugars detected in a monomeric form. Despite
      this high sugar recovery, this hydrolysate showed low ethanol yield (64% of
      theoretical yield) when fermented with a spent sulfite liquor-adapted strain of
      Saccharomyces cerevisiae. In contrast, most hydrolysates prepared at higher steam
      explosion severity showed comparable or higher ethanol yields. Furthermore, the
      hydrolysates prepared from bark-free feedstock showed better fermentability (87%
      of theoretical yield) despite containing higher concentration of known
      inhibitors. The ethanol yield from the hydrolysate prepared from a bark
      containing wood sample could be improved to 81% by an extra stage acid hydrolysis
      (121 degrees C for 1 h in 3% sulfuric acid). This extra stage acid hydrolysis and
      steam explosion at higher severity conditions seem to improve the fermentability
      of the hydrolysates by transforming certain inhibitory compounds present in the
      hydrolysates prepared from the bark-containing feedstock and thus lowering their
      inhibitory effect on the yeast used for the ethanol fermentation.

PMID- 11587581
TI  - Purification of docosahexaenoic acid ethyl ester using a silver-ion-immobilized
      porous hollow-fiber membrane module.
AB  - Docosahexaenoic acid ethyl ester (DHA-Et) was purified by adsorption on Ag-ion
      immobilized membranes via selective interaction between silver ion and carbon
      carbon double bonds of DHA-Et. Silver ions were immobilized onto sulfonic-acid
      group-containing porous hollow-fiber membranes at an Ag ion density of 1.4 mol/kg
      of membrane, and 30 membranes were housed in one module (inner diameter = 18 mm
      and effective length = 80 mm). The adsorption isotherms of DHA-Et in various
      organic solvents revealed that DHA-Et was adsorbed on the immobilized Ag ions
      with a DHA-Et/Ag ion molar binding ratio of 1/5 in methanol, and that
      acetonitrile was the solvent of choice for the elution of the adsorbed DHA-Et.
      Permeation of bonito oil ethyl ester solution in methanol through the Ag-ion
      immobilized hollow-fiber membrane module demonstrated that the displacement
      adsorption of other lower unsaturated fatty-acid ethyl esters by DHA-Et proceeded
      along the membrane thickness. The purity of DHA-Et was improved to 99 wt % by
      permeating first bonito oil ethyl ester containing 95 wt % DHA-Et and then
      acetonitrile through the module.

PMID- 11587582
TI  - Purification of recombinant brain derived neurotrophic factor using reversed
      phase displacement chromatography.
AB  - This work investigates the utility of RPLC displacement chromatography for the
      purification of recombinant brain derived neurotrophic factor (rHu-BDNF) from its
      variants and E. coli. protein (ECP) impurities. The closely associated variants
      (six in total) differ by one amino acid from the native BDNF and thus pose a
      challenging separation problem. Several operational parameters were investigated
      to study their effects on the yield of the displacement process. The results
      indicated that the concentration of trifluoroacetic acid (TFA) in the buffer was
      a key factor in achieving the desired purification. Displacement chromatography
      on an analytical scale column resulted in extremely high purity and yield in a
      single chromatographic step. The process was successfully scaled-up with respect
      to particle and column diameter. The production rate of a pilot scale RPLC
      displacement process was shown to be 23 times higher than the combined production
      rates of the current preparative ion exchange and hydrophobic interaction
      gradient elution steps that are used to remove variant and ECP impurities,
      respectively.

PMID- 11587583
TI  - Evaluation of eluents from separations of CD34+ cells from human cord blood using
      a commercial, immunomagnetic cell separation system.
AB  - Human CD34+ cells from cord blood were separated in a two-step process using a
      commercial, immunomagnetic cell retention system. The performance of the system
      was evaluated by analyzing a number of eluents from the separations with a number
      of analytical techniques. In addition to cell counts and flow cytometry analysis,
      a new experimental technique that is undergoing development, cell tracking
      velocimetry (CTV), was used. CTV measures the degree to which a cell is
      immunomagnetically labeled, known as the magnetophoretic mobility, of a
      population of cells on a cell-by-cell basis and presents the results in the form
      of a histogram similar to flow cytometry data. The average recovery and purity of
      CD34+ cells from 10 separations was 52% and 60%, respectively. CTV analysis
      indicated that the mean magnetophoretic mobility of the positively enriched CD34
      cells was 9.64 x 10(-5) mm3/T-A-s, while the mean mobility from negative eluents
      was -2.02 x 10(-6) mm3/T-A-s, very similar to the mobility of unlabeled cells.
      Within the positive eluents, the range of magnetophoretic mobility was
      approximately 50-fold, representing a plausible 50-fold range in surface CD34
      antigen expression. CTV analysis also indicated that in some separations,
      positive cells were not retained by the immunomagnetic cell retention system.
      Finally, preliminary studies indicate that monocytes might be a primary cause in
      the lower purities and recoveries seen in this study. It is suggested that the
      monocytes phagocytose the magnetic nanobeads and become sufficiently magnetized
      to be retained within the Miltenyi column, reducing the purity of the positive
      eluent.

PMID- 11587584
TI  - Comparison of protein fouling on heat-treated poly(vinyl alcohol), poly(ether
      sulfone) and regenerated cellulose membranes using diffuse reflectance infrared
      Fourier transform spectroscopy.
AB  - Poly(vinyl alcohol) (PVA) membranes for ultrafiltration were fabricated by heat
      treatment to separate macromolecules from microsolutes. PVA is a hydrophilic
      polymer with good mechanical properties because of its semicrystalline structure.
      The membranes were heat-treated at 100 degrees C for 1 h to increase their
      crystallinity and thereby their mechanical strength. The mechanical strength of
      the membranes was evaluated using a dynamic mechanical analyzer by measuring
      their compressive and tensile moduli. Membrane selectivities and protein fouling
      of heat-treated PVA membranes were compared to the commercial poly(ether sulfone)
      (PeS) and regenerated cellulose membranes. Myoglobin from horse skeletal muscle
      was used as a model protein, and L-tryptophan was used as a model microsolute.
      Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was used to
      identify protein fouling on the surfaces of these membranes under flow and
      nonflow conditions. It was found from the selectivity and DRIFTS studies that PVA
      membranes were more resistant to fouling than regenerated cellulose and PeS
      membranes.

PMID- 11587585
TI  - Feasibility study of repeated harvesting of menthol from biologically viable
      Mentha x piperata using ultrasonic extraction.
AB  - To potentially replace the conventional destructive extraction process, we have
      shown the feasibility of devising a novel technique that uses ultrasound to
      nonlethally and repeatedly extract menthol from biologically viable peppermint
      plants (Mentha x piperita). Our results show that plants ultrasonicated for 1 h
      at 22 degrees C in a standard 40 kHz ultrasonic bath could release approximately
      17.8 microg of menthol per gram of leaf tissue (2% of total product). The amount
      of menthol release increases with the time of treatment and is greatly affected
      by the temperature of the ultrasonic bath water. An increase from 2% to 12% of
      total product was observed when the temperature was increased from 22 degrees C
      to 39 degrees C. When the temperature effects were isolated, the mechanism of the
      product release was found to be that of cavitation. The treated plants remained
      viable and were ready for the subsequent ultrasound extraction after
      approximately 4 days of recuperation. However, the amount of product released is
      reduced in subsequent extractions. Scanning electron micrographs indicate that
      there are two mechanisms involved in extraction: (1) the diffusion of product
      through the cuticle of peppermint glandular trichomes and (2) the exudation of
      the product from broken and damaged trichomes. This study has shown the
      possibility of using an on-line ultrasonic, nondestructive extraction method to
      continuously release intracellular plant metabolites from the plants while
      maintaining the plant's viability.

PMID- 11587586
TI  - Computer-aided measurement of cell shortening and calcium transients in adult
      cardiac myocytes.
AB  - The contractile cycle of the cardiac myocyte is essentially controlled by the
      concentration of intracellular calcium ([Ca2+]i). Measurement of [Ca2+]i using
      Ca2+-dependent fluorescence and simultaneous monitoring of cell dynamics enable
      characterization of a variety of substances interacting with ion channels and
      contractile proteins. In this report we describe a novel method featuring up to
      480 frames/s for monitoring rapid changes in cellular calcium and cell length, in
      which every individual cycle allows effective evaluation of major cell
      parameters. Computers aid in determination of time to peak (in ms), time to 50%
      decrease (ms), diastolic Ca2+ (relative fluorescence units, rfu), systolic Ca2+
      (rfu), Ca2+ transients (rfu), DeltaCa2+/Delta(t) rise (rfu/s), and
      DeltaCa2+/Delta(t) fall (rfu/s). Contractile parameters are as follows: maximum
      cell length (microm), minimum cell length (microm), absolute cell shortening
      (microm), peak DeltaL/Delta(t) shortening (microm/s), and peak DeltaL/Delta(t)
      relaxation (microm/s). In summary, we succeeded in demonstrating that this system
      is a unique and valuable tool that allows simultaneous and accurate assessment of
      contractile parameters and of calcium movements of isolated adult cardiac
      myocytes.

PMID- 11587587
TI  - Effects of filtration seeding on cell density, spatial distribution, and
      proliferation in nonwoven fibrous matrices.
AB  - The cell seeding density and spatial distribution in a 3-D scaffold are critical
      to the morphogenetic development of an engineered tissue. A dynamic depth
      filtration seeding method was developed to improve the initial cell seeding
      density and spatial distribution in 3-D nonwoven fibrous matrices commonly used
      as tissue scaffolds. In this work, trophoblast-like ED27 cells were seeded in
      poly(ethylene terephthalate) (PET) matrices with various porosities (0.85-0.93).
      The effects of the initial concentration of cells in the suspension used to seed
      the PET matrix and the pore size of the matrix on the resulting seeding density
      and subsequent cell proliferation and tissue development were studied. Compared
      to the conventional static seeding method, the dynamic depth-filtration seeding
      method gave a significantly higher initial seeding density (2-4 x 10(7) vs 4 x
      10(6) cells/cm3), more uniform cell distribution, and a higher final cell density
      in the tissue scaffold. The more uniform initial cell spatial distribution from
      the filtration seeding method also led to more cells in S phase and a prolonged
      proliferation period. However, both uniform spatial cell distribution and the
      pore size of the matrices are important to cell proliferation and morphological
      development in the seeded tissue scaffold. Large-pore matrices led to the
      formation of cell aggregates and thus might reduce cell proliferation. The
      dynamic depth-filtration seeding method is better in providing a higher initial
      seeding density and more uniform cell distribution and is easier to apply to
      large tissue scaffolds. A depth-filtration model was also developed and can be
      used to simulate the seeding process and to predict the maximum initial seeding
      densities in matrices with different porosities.

PMID- 11587588
TI  - Degradation of partially oxidized alginate and its potential application for
      tissue engineering.
AB  - Alginate has been widely used in a variety of biomedical applications including
      drug delivery and cell transplantation. However, alginate itself has a very slow
      degradation rate, and its gels degrade in an uncontrollable manner, releasing
      high molecular weight strands that may have difficulty being cleared from the
      body. We hypothesized that the periodate oxidation of alginate, which cleaves the
      carbon-carbon bond of the cis-diol group in the uronate residue and alters the
      chain conformation, would result in promoting the hydrolysis of alginate in
      aqueous solutions. Alginate, oxidized to a low extent (approximately 5%),
      degraded with a rate depending on the pH and temperature of the solution. This
      polymer was still capable of being ionically cross-linked with calcium ions to
      form gels, which degraded within 9 days in PBS solution. Finally, the use of
      these degradable alginate-derived hydrogels greatly improved cartilage-like
      tissue formation in vivo, as compared to alginate hydrogels.

PMID- 11587589
TI  - Population dynamics of a continuous fermentation of recombinant Saccharomyces
      cerevisiae using flow cytometry.
AB  - The plasmid instability of genetically modified microorganisms during prolonged
      bioreactor operations is one of the major problems to be overcome in the
      production of recombinant proteins. The use of flow cytometry to monitor a
      fermentation process with recombinant cells in a CSTR is reported here. This
      technique has been applied to determine the fraction of plasmid-bearing cells
      (P+) of a recombinant Saccharomyces cerevisiae strain harboring the EXG1 gene in
      a continuous stirred tank bioreactor with a working volume of 2 L. The different
      levels in the expression of the EXG1 gene, which encodes the enzyme exo-beta
      glucanase, were used to determine the P+ fraction. Other parameters such as
      viability, cellular protein, cell size and structure were also monitored using
      flow cytometry. This technique has two main advantages over the conventional
      method of determining the P+ fraction (plating in selective and non-selective
      solid media): (a) it takes a very short period of time to obtain a measurement
      that provides multiple parametric information; and (b) it is more representative
      of the bioreactor cell population since it can analyze thousands of cells in the
      same sample. A continuous operation (432 h) with the recombinant strain in a CSTR
      was carried out to test the application of this technique. Measurements of
      cellular exo-beta-glucanase activity and cellular protein content closely
      correlates to the measured fraction of plasmid-containing cells in the
      population. Moreover, the standard deviation of the fraction of P+ cells
      determined using this technique was very low (about 2%). Recombinant protein
      production also increased the size of the yeast cells, whereas the recombinant
      cells also had a more complex internal structure than the non-recombinant host
      strain.

PMID- 11587590
TI  - Microfabricated polymer chip for capillary gel electrophoresis.
AB  - A polymer (PDMS: poly(dimethylsiloxane)) microchip for capillary gel
      electrophoresis that can separate different sizes of DNA molecules in a small
      experimental scale is presented. This microchip can be easily produced by a
      simple PDMS molding method against a microfabricated master without the use of
      elaborate bonding processes. This PDMS microchip could be used as a single use
      device unlike conventional microchips made of glass, quartz or silicon. The
      capillary channel on the chip was partially filled with agarose gel that can
      enhance separation resolution of different sizes of DNA molecules and can shorten
      the channel length required for the separation of the sample compared to
      capillary electrophoresis in free-flow or polymer solution format. We discuss the
      optimal conditions for the gel preparation that could be used in the
      microchannel. DNA molecules were successfully driven by an electric field and
      separated to form bands in the range of 100 bp to 1 kbp in a 2.0% agarose-filled
      microchannel with 8 mm of effective separation length.

PMID- 11587591
TI  - Measuring the interaction forces between protein inclusion bodies and an air
      bubble using an atomic force microscope.
AB  - Interaction forces between protein inclusion bodies and an air bubble have been
      quantified using an atomic force microscope (AFM). The inclusion bodies were
      attached to the AFM tip by covalent bonds. Interaction forces measured in various
      buffer concentrations varied from 9.7 nN to 25.3 nN (+/- 4-11%) depending on pH.
      Hydrophobic forces provide a stronger contribution to overall interaction force
      than electrostatic double layer forces. It also appears that the ionic strength
      affects the interaction force in a complex way that cannot be directly predicted
      by DLVO theory. The effects of pH are significantly stronger for the inclusion
      body compared to the air bubble. This study provides fundamental information that
      will subsequently facilitate the rational design of flotation recovery system for
      inclusion bodies. It has also demonstrated the potential of AFM to facilitate the
      design of such processes from a practical viewpoint.

PMID- 11587592
TI  - Changes in Saccharomyces cerevisiae development induced by magnetic fields.
AB  - Saccharomyces cerevisiae cultures exposed to 110 mT and 220 mT steady magnetic
      fields (SMF) were studied to observe eventual induced growth alterations and
      changes in metabolic activity. Cell mass (biomass) growth was evaluated by light
      spectrometry, and metabolic alterations were estimated on the basis of the CO2
      pressure produced and by the culture media pH changes, measured at the beginning
      and the end of the observation. The yeast strain DAUFPE-1012, cultivated in a
      nonaerated liquid agar Sabouraud glucose medium, was exposed to SMF generated by
      NdFeBr magnets. Results showed alterations induced by 220 mT SMF as an increment
      in cell proliferation (1.84%) and an increased CO2 production (36.1%) as compared
      to control groups. Furthermore, the initial-to-final pH difference in 220 mT SMF
      exposed cultures was higher than the 110 mT SMF and the control values. The whole
      acidification and the rise in CO2 production observed after 220 mT SMF exposure
      did not correspond to the biomass growth values, as compared to the other
      cultures, and was apparently provoked by a enhancement in the cellular metabolic
      rate. This technique becomes very promising for future biotechnological
      applications in fermentative processes.

PMID- 11587593
TI  - Protein modifications during antiviral heat bioprocessing and subsequent storage.
AB  - Antiviral heat treatment is routinely used in the bioprocessing of therapeutic
      proteins as a means of reducing viral load. However, in protein formulations
      containing sucrose this form of bioprocessing can lead to protein modifications.
      Using a model protein, hen egg white lysozyme, we investigated the effects of
      antiviral heat treatments in the presence of sucrose on protein integrity during
      subsequent long-term protein storage. Although heat treatment alone resulted in
      protein modification, subsequent medium- to long-term storage of both lyophilized
      and liquid samples at room temperature or above led to further protein
      modifications. The majority of these modifications were due to the formation of
      glycation and advanced glycation end products via the reaction of reducing sugars
      and their autoxidation products (derived from hydrolyzed sucrose) with function
      groups on the protein surface. These findings have implications for the
      improvement of therapeutic protein bioprocessing to ensure protein product
      quality.

PMID- 11587594
TI  - Sponsorship, authorship, and accountability.

PMID- 11587596
TI  - The otolaryngology research paradox.
AB  - OBJECTIVE: To determine the attitude toward and the state of research within the
      field of otolaryngology-head and neck surgery. DESIGN: A questionnaire was sent
      to the chairpersons of departments of otolaryngology where residency training is
      provided. PARTICIPANTS AND SETTING: Program directors of academic otolaryngology
      training programs. MAIN OUTCOME MEASURE: Responses to questionnaire. RESULTS:
      Questionnaires were sent to 95 programs from which 86 responses were received.
      Respondents believed strongly that research was important to the specialty. Only
      two thirds of the full-time clinical faculty, however, do research, and on
      average they devote only 17% of their time to this activity. About a third of
      those doing research have funding, and the National Institutes of Health support
      only 12% of clinician-investigators. Although program directors believe that
      clinicians should do research, three fourths stated that clinicians were too busy
      to accomplish this goal. Surprisingly, half of the respondents were unaware of
      residency programs that offered 2 years of research training, aimed to develop
      clinician-investigators, who can become competitive for attainment of research
      funding. CONCLUSIONS: Although leaders within our specialty believe that research
      is important, clinicians are not provided with enough time to conduct research.
      Furthermore, pathways that would enhance their competitiveness to obtain research
      funding are not recommended to our future clinicians.

PMID- 11587597
TI  - The value of research in otolaryngology-head and neck surgery.

PMID- 11587598
TI  - The impact of airbags and seat belts on the incidence and severity of
      maxillofacial injuries in automobile accidents in New York State.
AB  - OBJECTIVE: To evaluate the effect driver-side and passenger-side airbags have had
      on the incidence and severity of maxillofacial trauma in victims of automobile
      accidents. DESIGN: Retrospective analysis of all automobile (passenger cars and
      light trucks) accidents reported in 1994. SETTING: New York State. PATIENTS: Of
      the 595910 individuals involved in motor vehicle accidents in New York in 1994,
      377054 individuals were initially selected from accidents involving cars and
      light trucks. Of this subset, 164238 drivers and 62755 right front passengers
      were selected for analysis. MAIN OUTCOME MEASURES: Each case is described in a
      single record with approximately 100 variables describing the accident, eg,
      vehicle, safety equipment installed and utilized or deployed, occupant position,
      patient demographics, International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM) diagnoses, and procedural treatments rendered. A
      maxillofacial trauma severity scale was devised, based on the ICD-9-CM diagnoses.
      RESULTS: Individuals using airbags and seat belts sustained facial injuries at a
      rate of 1 in 449, compared with a rate of 1 in 40 for individuals who did not use
      seat belts or airbags (P<.001). Those using airbags alone sustained facial
      injuries at the intermediate rate of 1 in 148, and victims using seat belts
      without airbags demonstrated an injury rate of 1 in 217 (P<.001). CONCLUSION: Use
      of driver-side airbags, when combined with use of seat belts, has resulted in a
      decrease in the incidence and severity of maxillofacial trauma.

PMID- 11587599
TI  - Randomized trial of amplification strategies.
AB  - BACKGROUND: Little is known about quality of life after the use of specific types
      of hearing aids, so it is difficult to determine whether technologies such as
      programmable circuits and directional microphones are worth the added expense.
      OBJECTIVE: To compare the effectiveness of an assistive listening device, a
      nonprogrammable nondirectional microphone hearing aid, with that of a
      programmable directional microphone hearing aid against the absence of
      amplification. DESIGN: Randomized controlled trial. SETTING: Audiology clinic at
      the VA Puget Sound Health Care System, Seattle, Wash. PATIENTS: Sixty veterans
      with bilateral moderate to severe sensorineural hearing loss completed the trial.
      Half the veterans (n = 30) had hearing loss that the Veterans Affairs clinic
      determined was rated as "service connected," which meant that they were eligible
      for Veterans Affairs-issued hearing aids. INTERVENTION: Veterans with non-service
      connected hearing loss, who were ineligible for Veterans Affairs-issued hearing
      aids, were randomly assigned to no amplification (control arm) or to receive an
      assistive listening device. Veterans with service-connected loss were randomly
      assigned to receive either the nonprogrammable hearing aid that is routinely
      issued ("conventional") or a programmable aid with a directional microphone
      ("programmable"). MAIN OUTCOME MEASURES: Hearing-related quality of life, self
      rated communication ability, adherence to use, and willingness to pay for the
      amplification devices (measured 3 months after fitting). RESULTS: Clear
      distinctions were observed between all 4 arms. The mean improvement in hearing
      related quality of life (Hearing Handicap Inventory for the Elderly) scores was
      small for control patients (2.2 points) and patients who received an assistive
      listening device (4.4 points), excellent for patients who received a conventional
      device (17.4 points), and substantial for patients who received a programmable
      device (31.1 points) (P<.001 by the analysis of variance test). Qualitative
      analyses of free-text diary entries, self-reported communication ability
      (Abbreviated Profile of Hearing Aid Benefit) scores, adherence to hearing aid
      use, and willingness to pay for replacement devices showed similar trends.
      CONCLUSIONS: A programmable hearing aid with a directional microphone had the
      highest level of effectiveness in the veteran population. A nonprogrammable
      hearing aid with an omnidirectional microphone was also effective compared with
      an assistive listening device or no amplification.

PMID- 11587600
TI  - Role of central preprogramming in dynamic visual acuity with vestibular loss.
AB  - OBJECTIVE: To determine the contribution of central preprogramming of eye
      movements to dynamic visual acuity (DVA) during head movement in patients with
      vestibular hypofunction. STUDY DESIGN: Prospective, clinical study. SETTING:
      Tertiary care, academic hospitals. PARTICIPANTS: Twenty-six healthy subjects and
      20 patients with unilateral (UVL) and 7 with bilateral vestibular loss (BVL) (age
      range, 20-86 years). INTERVENTIONS: Diagnostic interventions, including caloric
      and rotational chair testing. MAIN OUTCOME MEASURE: Measurements of DVA during
      predictable (DVA-predictable) and unpredictable (DVA-unpredictable) head
      movements using a computerized test. RESULTS: There was a difference between DVA
      predictable and DVA-unpredictable scores in all groups (P<.02). The difference
      between DVA-predictable and DVA-unpredictable scores for the BVL group was
      significantly greater than that for the other groups (P<.005). Age was a
      significant factor in DVA-unpredictable scores for the healthy subjects (P<.001)
      and UVL group (P<.02). Comparisons of DVA between groups were significant
      (P<.03), with the following exceptions: UVL group for head movements toward the
      unaffected side for DVA-predictable and DVA-unpredictable scores, compared with
      healthy subjects, and UVL group for head movements toward the affected side for
      DVA-predictable scores, compared with the BVL group. CONCLUSIONS: Unpredictable
      head movements cause a greater decrement in visual acuity than do predictable
      head movements. This suggests that central programming of eye movements and/or
      efference copy contributes to gaze stability during predictable head movements in
      healthy subjects and patients with vestibular hypofunction. Patients with BVL use
      central programming of eye movements to maintain gaze stability more than do
      healthy subjects or patients with UVL.

PMID- 11587601
TI  - Selective cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization.
AB  - OBJECTIVE: To determine if selective reinnervation of the cricothyroid muscle
      could be achieved with muscle-nerve-muscle neurotization. DESIGN: Case series.
      SETTING: Tertiary referral center. PATIENTS: Three consecutive patients with high
      vagal lesions that resulted in unilateral laryngeal paralysis. INTERVENTIONS:
      Patients underwent laryngeal reinnervation with ansa hypoglossi to recurrent
      laryngeal nerve anastomosis. In addition, patients underwent selective
      cricothyroid muscle reinnervation by muscle-nerve-muscle neurotization technique.
      MAIN OUTCOME MEASURES: Objective and subjective improvement in voice quality and
      electromyographic evidence of selective reinnervation of the cricothyroid muscle.
      RESULTS: All patients recovered normal or near-normal speaking voice and had
      normal objective measures of voice quality. They also showed electromyographic
      evidence of cricothyroid muscle reinnervation. CONCLUSION: The muscle-nerve
      muscle neurotization technique was successful in providing selective
      reinnervation of the cricothyroid muscle in our 3 patients.

PMID- 11587602
TI  - Therapeutic electrical stimulation of the hypoglossal nerve in obstructive sleep
      apnea.
AB  - BACKGROUND: Hypoglossal nerve stimulation has been demonstrated to relieve upper
      airway obstruction acutely, but its effect on obstructive sleep apnea is not
      known. OBJECTIVE: To determine the response in obstructive sleep apnea to
      electrical stimulation of the hypoglossal nerve. METHODS: Eight patients with
      obstructive sleep apnea were implanted with a device that stimulated the
      hypoglossal nerve unilaterally during inspiration. Sleep and breathing patterns
      were examined at baseline before implantation and after implantation at 1, 3, and
      6 months and last follow-up. RESULTS: Unilateral hypoglossal nerve stimulation
      decreased the severity of obstructive sleep apnea throughout the entire study
      period. Specifically, stimulation significantly reduced the mean apnea-hypopnea
      indices in non-rapid eye movement (mean +/- SD episodes per hour, 52.0 +/- 20.4
      for baseline nights and 22.6 +/- 12.1 for stimulation nights; P<.001) and rapid
      eye movement (48.2 +/- 30.5 and 16.6 +/- 17.1, respectively; P<.001) sleep and
      reduced the severity of oxyhemoglobin desaturations. With improvement in sleep
      apnea, a trend toward deeper stages of non-rapid eye movement sleep was observed.
      Moreover, all patients tolerated long-term stimulation at night and did not
      experience any adverse effects from stimulation. Even after completing the study
      protocol, the 3 patients who remained free from stimulator malfunction continued
      to use this device as primary treatment. CONCLUSION: The findings demonstrate the
      feasibility and therapeutic potential for hypoglossal nerve stimulation in
      obstructive sleep apnea.

PMID- 11587603
TI  - Hyoid movement during swallowing in older patients with dysphagia.
AB  - OBJECTIVES: To describe the timing, coordination, and extent of hyoid movement in
      a population of older adults with dysphagia and to evaluate the effect of hyoid
      movement on upper esophageal sphincter opening. DESIGN: A retrospective review of
      dynamic swallow studies performed between January 1996 and December 1999 was
      done. SUBJECTS: Patients included in the study were 65 years or older, without an
      obvious medical or surgical cause for their dysphagia. Timing and distance
      measures of hyoid movement from the patient population were compared with those
      from 60 younger (range, 18-62 years) and 23 older (range 67-83 years) control
      subjects without dysphagia using 1-way analysis of variance. Analysis of the
      effect of hyoid movement on upper esophageal sphincter opening was performed
      using contingency tables. RESULTS: In an older population with dysphagia, the
      coordination of swallowing gestures and bolus timing was intact, hyoid elevation
      was slow, and the duration of maximal hyoid elevation was reduced, but
      appropriate for the age of the patients. The hyoid bone elevated farther than
      normal for small bolus sizes, but the patients were unable to maintain this
      strategy in larger bolus swallows. CONCLUSION: An increased extent of hyoid
      displacement in older patients with dysphagia may represent a necessary
      compensation designed to minimize the effect of the short duration of hyoid
      elevation on the upper esophageal sphincter opening.

PMID- 11587604
TI  - How do the cervical plexus and the spinal accessory nerve contribute to the
      innervation of the trapezius muscle? As seen from within using Sihler's stain.
AB  - OBJECTIVE: To determine how the spinal accessory nerve and the trapezius branches
      of the cervical plexus contribute to the innervation of each of the 3 parts of
      the trapezius muscle. Special emphasis was placed on the nerve supply of the
      clinically most important descending part of the muscle. DESIGN: Anatomical
      analysis of the distribution of the cervical plexus and spinal accessory nerve
      branches in the human trapezius muscle. MATERIALS: Twenty-two trapezius muscles
      from 11 perfusion-fixed human cadavers ranging in age from 66 to 92 years (mean,
      81.7 years). INTERVENTIONS: The specimens were dissected free and macerated,
      decalcified, and stained according to Sihler's technique for about 6 weeks. The
      translucent, stained muscles were then backlit, and the findings were documented
      photographically and by schematic drawings. RESULTS: In all 22 muscles, the
      innervation of each of the 3 parts of the trapezius muscle was seen. In all
      muscles investigated, the nerve supply to the descending part of the muscle
      consisted of a single fine branch of the spinal accessory nerve, whereas the
      transverse and ascending parts were innervated by both the spinal accessory nerve
      and the trapezius branches of the cervical plexus. CONCLUSION: Our results,
      especially those involving the descending part of the trapezius muscle, may help
      to minimize the rate of unexpected trapezius muscle paresis after surgery of the
      neck.

PMID- 11587605
TI  - Frameless optical computer-aided tracking of a microscope for otorhinology and
      skull base surgery.
AB  - OBJECTIVES: To integrate a digitally controlled operating microscope without a
      laser autofocus system into a frameless optical computer-aided surgery system and
      to test the accuracy and usability of this system in otorhinological surgery.
      DESIGN: Experimental study and case series. SETTING: Department of Oto-Rhino
      Laryngology, Head and Neck Surgery, Inselspital, and the Maurice E. Muller
      Institute for Biomechanics, University of Bern, Bern, Switzerland. PATIENTS:
      Eight computer-aided microscopic surgical procedures were performed between
      January and October 2000 on patients with various diseases of the anterior and
      lateral skull base. RESULTS: The practical accuracy of the navigated microscope
      on the lateral side of a cadaver skull was 2.27 +/- 0.25 mm and on the anterior
      side of the same skull was 2.07 +/- 0.35 mm. In all 8 cases of computer-aided
      microscopic surgery, no complications occurred. Clinical inaccuracy was 2 to 3
      mm. CONCLUSION: Integration of a low-cost, non-laser autofocus microscope into
      our computer-aided surgery system was successfully performed and offers surgeons
      the ability to combine the precise optics of the operating microscope with the
      localization power of a computer-aided system.

PMID- 11587606
TI  - Fibrous dysplasia involving the skull base and temporal bone.
AB  - OBJECTIVE: To gain a broader appreciation of the clinical presentation, operative
      treatment, and outcome of patients with fibrous dysplasia involving the skull
      base. DESIGN: Retrospective review of a clinical case series. SETTING: A single
      tertiary academic medical center. PATIENTS: Twenty-one patients with
      histopathologically confirmed fibrous dysplasia involving the skull base cared
      for over a 15-year-period (1983-1998). MAIN OUTCOME MEASURES: Clinical and
      radiographic location of the fibrous dysplasia lesions within the skull base,
      clinical presentation, surgical intervention, and clinical outcome were tabulated
      for each patient. RESULTS: The ethmoids were most commonly involved (71%),
      followed by the sphenoid (43%), frontal (33%), maxilla (29%), temporal (24%),
      parietal (14%), and occipital (5%) bones. The most common presenting features
      included atypical facial pain and headache, complaints referable to the sinuses,
      proptosis and diplopia, hearing loss, and facial numbness. Surgical treatment,
      guided by clinical presentation, ranged from simple biopsy with conservative
      follow-up to craniofacial resection. CONCLUSIONS: Fibrous dysplasia can present
      in myriad ways within the skull base. Modern imaging modalities and
      histopathologic analysis have made diagnosis relatively straightforward. Surgery,
      particularly in such a challenging region as the skull base, should be reserved
      for patients with functional impairment or a cosmetic deformity. Because of the
      benign nature of the condition, the surgery itself should be relatively
      conservative, with the primary goal being preservation of existing function.

PMID- 11587607
TI  - Age dependence of cellular properties of human septal cartilage: implications for
      tissue engineering.
AB  - BACKGROUND: The persistent need for cartilage replacement material in head and
      neck surgery has led to novel cell culture methods developed to engineer
      cartilage. Currently, there is no consensus on an optimal source of cells for
      these endeavors. OBJECTIVES: To evaluate human nasal cartilage as a potential
      source of chondrocytes and to determine the effect of donor age on cellular and
      proliferation characteristics. SUBJECTS: Nasal cartilage specimens were obtained
      after reconstructive surgery from 46 patients ranging in age from 15 to 60 years.
      METHODS: Specimens were weighed and chondrocytes were isolated by digestion in
      0.2% collagenase type II for 16 hours. Cells were maintained in primary cultures
      until confluency, then seeded onto polylactic acid-polyglycolic acid scaffolds.
      Seeding efficiency was determined by quantification of DNA content of seeded
      constructs by means of Hoechst dye 33258. Specimen weights, cell yields, cell
      content, and doubling time were also measured and correlated to donor age.
      RESULTS: Mean (+/-SD) cartilage mass obtained (648 +/- 229 mg) is higher than
      from typical biopsy specimens of auricular cartilage, and the cellular
      characteristics show a higher proliferation rate than auricular chondrocytes.
      Cell yield increased with age, while doubling time decreased with age in samples
      from patients ranging from 15 to 60 years old. CONCLUSIONS: The use of nasal
      septal cartilage as a source of cells for tissue engineering may be valid over a
      wide range of patient ages. The large tissue yield and consequent cell yield make
      this tissue a potential starting source of chondrocytes for large-volume tissue
      engineered implants.

PMID- 11587608
TI  - Correlation of expression of cyclooxygenase-2, vascular endothelial growth
      factor, and peroxisome proliferator-activated receptor delta with head and neck
      squamous cell carcinoma.
AB  - Cyclooxygenase (COX) is the rate-limiting enzyme in the formation of
      prostaglandins from arachidonic acid. COX exists in 2 isoforms, COX-1 and COX-2.
      These isoforms are encoded by separate genes and demonstrate cell-specific
      expression and regulation. Peroxisome proliferator-activated receptor delta
      (PPARdelta) is a nuclear transcription factor that is activated by prostacyclin.
      Vascular endothelial growth factor (VEGF) is a proangiogenic factor that is up
      regulated in various tumors. Vascular endothelial growth factor has been shown to
      interact with COX-derived prostaglandins in angiogenesis. To better understand
      the roles of these genes in head and neck squamous cell carcinoma (HNSCCA), we
      examined the differential expression of the COX1, COX2, VEGF, and PPARdelta genes
      in these tumors. Tissue samples from patients with HNSCCA were analyzed for COX
      1, COX-2, VEGF, and PPARdelta messenger RNAs (mRNAs) by in situ hybridization.
      COX-1 and COX-2 mRNAs were also evaluated with Northern blot hybridization.
      Immunohistochemistry was used to analyze for COX-2 and PPARdelta proteins.
      Results showed focal areas of accumulation for COX-2, VEGF, and PPARdelta but not
      COX-1 in human HNSCCA. Northern blot hybridization showed higher levels of COX-2
      mRNA in HNSCCA than in normal tissue. This suggests a supportive role of COX-2 in
      development and/or progression of HNSCCA. In addition, PPARdelta may be a
      receptor for COX-2-produced prostaglandins in HNSCCA. There is a potential role
      for selective COX-2 inhibitors in the treatment of these lesions.

PMID- 11587609
TI  - Topical mitomycin application after laryngotracheal reconstruction: a randomized,
      double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To explore the effect of mitomycin treatment on the pediatric airway
      following laryngotracheal reconstruction. DESIGN: Randomized, double-blind,
      placebo-controlled trial. PATIENTS: Children aged 2 to 17 years with subglottic
      or upper tracheal stenosis undergoing laryngotracheal reconstruction at a single,
      tertiary care, children's hospital. INTERVENTION: At the time of extubation or
      stent removal, the children underwent bronchoscopy and 0.4 mg/mL (2 mL of a 0.2
      mg/mL solution of either mitomycin or an equal volume of isotonic sodium chloride
      was directly applied to the subglottic region for a single application of 2
      minutes. These children then underwent interval endoscopy at 2 weeks, 6 weeks,
      and 3 months postoperatively for assessment of their airways. RESULTS:
      Granulation tissue was graded on a scale of 0 (none) to 4 (near-total or total
      occlusion). Videotapes of endoscopies were independently observed and graded by 3
      pediatric otolaryngology fellows with a subsequent interobserver agreement of
      91.6%. The results were then dichotomized to represent a single cohort in which
      further surgical intervention would be required and another separate cohort in
      which further surgery would not be required. At the 1-year mark, interim analysis
      was performed by a Data Safety and Monitoring Committee. At this time, 13
      children had been randomized to the mitomycin-treated arm of the study and 11
      children to the placebo-treated arm. A 2-tailed Fisher exact test revealed a
      value of 1.00. The Data Monitoring and Safety Committee advised that the trial
      should be stopped because the distributions between the 2 populations were almost
      identical. CONCLUSION: We cannot reject the null hypothesis that a single topical
      dose of mitomycin exerts an equal benefit as does isotonic sodium chloride when
      applied to the pediatric airway after laryngotracheal reconstruction.

PMID- 11587610
TI  - Ropivacaine with or without clonidine improves pediatric tonsillectomy pain.
AB  - OBJECTIVE: To determine if preemptive analgesia with ropivacaine hydrochloride
      with or without clonidine hydrochloride decreases pain and hastens recovery after
      tonsillectomy. DESIGN: Prospective, randomized, triple-blinded trial. SETTING:
      University referral center; pediatric ambulatory practice. PARTICIPANTS: Sixty
      four children, aged 3 to 15 years, undergoing tonsillectomy. INTERVENTIONS:
      Patients received injections in the tonsillar fossae of isotonic sodium chloride,
      ropivacaine, or ropivacaine plus clonidine prior to tonsil excision. MAIN OUTCOME
      MEASURES: Visual analogue (pain) scale scores at rest and when drinking, opioid
      use, recovery time to normal activity, and incidence of symptoms such as otalgia.
      RESULTS: Pain was reduced on postoperative day 0 in the ropivacaine-treated and
      ropivacaine plus clonidine-treated groups as compared with the isotonic sodium
      chloride-treated group (P<.05). Pain was also decreased in the ropivacaine plus
      clonidine-treated group on postoperative days 3 and 5 (P<.05). Intravenous
      narcotic use was decreased on day 0 in the ropivacaine-treated and ropivacaine
      plus clonidine-treated groups (P<.05). Cumulative codeine use was similar at day
      3 for all patients, but was decreased at day 5 in the ropivacaine plus clonidine
      treated group (P<.05). The incidence of otalgia decreased from 89% (16/18) in the
      isotonic sodium chloride-treated group to 63% (12/19) in the ropivacaine-treated
      and 61%(11/18) in the ropivacaine plus clonidine-treated groups (P<.01). Recovery
      to normal activity was shortened from 8.1 +/- 1.6 days to 5.8 +/- 2.9 days (mean
      +/- SD) in the isotonic sodium chloride-treated and ropivacaine plus clonidine
      treated groups, respectively (P =.03). CONCLUSION: Preincisional injection of
      ropivacaine with clonidine prior to tonsillectomy has a preemptive analgesic
      effect that outlasts the local anesthetic and decreases pain, opioid use, and the
      time to return to normal activity.

PMID- 11587611
TI  - Posttonsillectomy hemorrhage: what is it and what should be recorded?
AB  - OBJECTIVES: To report on our incidence of posttonsillectomy hemorrhage and to
      define what constituted posttonsillectomy bleeding. DESIGN: Retrospective study.
      SETTING: Tertiary care children's hospital and a local satellite facility.
      PATIENTS: A series of 1438 consecutive patients who had undergone either
      tonsillectomy or adenotonsillectomy between January 1, 1999, and December 31,
      1999. INTERVENTION: During this period, parents were instructed to return with
      their children for clinical evaluation if any blood was seen in the postoperative
      period. MAIN OUTCOME MEASURES: Postoperative day of evaluation, age, sex,
      location of bleeding, management strategy, length of hospital admission, and any
      bleeding disorders were noted for each patient. RESULTS: A total of 112 patients
      underwent evaluation 134 times. Of these patients, 96 required only 1 evaluation
      and 16 required more than 1 evaluation. All patients who had more than 1
      evaluation required intervention. The total number of children requiring
      intervention for posttonsillectomy hemorrhage was 51 (3.5%) of the 1438 patients.
      Female patients were more likely than male patients to return for evaluation.
      Patients who were 12 years and older were the most likely and those 3 years and
      younger were the least likely to have posttonsillectomy hemorrhage. The most
      common time from surgery to initial evaluation for hemorrhage was 6 days.
      CONCLUSIONS: By reviewing our own criteria for defining and recording
      posttonsillectomy hemorrhage, we conclude that posttonsillectomy hemorrhage is
      defined differently in the literature. This supports the need for a standard
      definition to allow for direct comparisons.

PMID- 11587612
TI  - Injection of local anesthetic in tonsillectomy.

PMID- 11587613
TI  - Bupivacaine injection to control tonsillectomy pain.

PMID- 11587614
TI  - Concerns with bupivacaine injection.

PMID- 11587615
TI  - Pathology quiz case: nodular sclerosing Hodgkin lymphoma.

PMID- 11587616
TI  - Radiology quiz case: nasopalatine duct cyst.

PMID- 11587617
TI  - Radiofrequency tonsil reduction.

PMID- 11587619
TI  - Stethoscope-tuning fork test (Ahmadizadeh test) for diagnosis of sinusitis.

PMID- 11587618
TI  - Aspirin desensitization for chronic hyperplastic sinusitis, nasal polyposis, and
      asthma triad.

PMID- 11587620
TI  - Pillow otalgia.

PMID- 11587621
TI  - Family planning in a stemborer parasitoid: sex ratio, brood size and size-fitness
      relationships in Parallorhogas pyralophagus (Hymenoptera: Braconidae), and
      implications for biological control.
AB  - Various aspects were studied of the brood size and sex allocation strategies, and
      of size-fitness relationships in Parallorhogas pyralophagus (Marsh), a gregarious
      ectoparasitoid of Eoreuma loftini Dyar. Brood size was significantly correlated
      with host size; larger hosts were allocated larger broods. Brood sex ratios were
      fixed precisely at 1 male per 4 females, and eggs were likely to be deposited in
      that order; differential mortality did not contribute to this precise sex ratio.
      The sex allocation strategy of P. pyralophagus is likely to conform to strict,
      i.e. single foundress, local mate competition. Adoption of this strategy is
      probably influenced by a limited insemination capacity of males; a smaller
      proportion of females (0.09 vs. 0.21) remained virgin in broods with precise or
      higher sex ratios (> or = 0.20 males) relative to broods with lower than precise
      sex ratios (< 0.20 males). Moreover, all females were inseminated in most broods
      (60%) with precise or higher sex ratios, whereas this did not occur in broods
      with lower than precise sex ratios. The hypothesized occurrence of strict local
      mate competition in P. pyralophagus was supported also by observations that: (i)
      offspring brood sex ratios were independent of maternal brood sex ratios and
      number of parental females concurrently allocating offspring to a group of hosts,
      and; (ii) the rate of superparasitism under no-choice conditions was low
      (approximately 20%), suggesting that rates of outbreeding in the field are low.
      Other results suggested that fitness in P. pyralophagus was correlated with adult
      size; longevity and reproductive capacity both increased with adult size in males
      and females. However, adult size may be more important for females than for males
      because the differences in reproductive capacity between the largest and smallest
      individuals was up to 7.3 times greater in females versus < 2 times in males.

PMID- 11587622
TI  - Bioassay and biochemical analyses of insecticide resistance in southern African
      Anopheles funestus (Diptera: Culicidae).
AB  - Anopheles funestus Giles has been implicated as a major malaria vector in sub
      Saharan Africa where pyrethroid insecticides are widely used in agriculture and
      public health. Samples of this species from northern Kwazulu/Natal in South
      Africa and the Beluluane region of southern Mozambique showed evidence of
      resistance to pyrethroid insecticides. Insecticide exposure, synergist and
      biochemical assays conducted on A. funestus suggested that elevated levels of
      mixed function oxidases were responsible for the detoxification of pyrethroids in
      resistant mosquitoes in these areas. The data suggested that this mechanism was
      also conferring cross-resistance to the carbamate insecticide propoxur.

PMID- 11587623
TI  - Evaluation of diets for the development and reproduction of Franklinothrips
      orizabensis (Thysanoptera: Aeolothripidae).
AB  - The suitability of ten diets for the development and reproduction of
      Franklinothrips orizabensis Johansen, the key natural enemy of Scirtothrips
      perseae Nakahara, a pest of California grown avocados, was determined in the
      laboratory. The experimental diets evaluated were: (i) irradiated Ephestia
      kuehniella Zeller eggs; (ii) irradiated E. kuehniella eggs and avocado pollen;
      (iii) Tetranychus pacificus McGregor eggs; (iv) T. pacificus eggs and avocado
      pollen; (v) irradiated E. kuehniella eggs and T. pacificus eggs; (vi) irradiated
      E. kuehniella eggs, T. pacificus eggs and avocado pollen; (vii) Scirtothrips
      perseae; (viii) Heliothrips haemorrhoidalis (Bouche); (ix) avocado pollen; and
      (x) a young avocado leaf. Franklinothrips orizabensis larvae were unable to
      develop to adulthood on diets 9 and 10. The remaining eight diets supported
      complete development of F. orizabensis, but only diets 1, 2, 5, 6, 7 and 8
      produced fecund females. On diet 5, F. orizabensis exhibited high larval to adult
      survivorship (90%), mated females exhibited highest daily and lifetime fecundity,
      and the progeny of mated females were female biased (53%). Analysis of jackknife
      estimates of net reproduction (Ro), intrinsic rate of increase (rm), and finite
      rate of increase (lambda) were all significantly greater for F. orizabensis
      reared on irradiated E. kuehniella eggs and T. pacificus eggs (i.e. diet 5) than
      corresponding values for other diets on which female F. orizabensis were able to
      complete development and reproduce. Incorporation of avocado pollen into diets
      had an adverse effect on demographic statistics for F. orizabensis, and low
      quality diets resulted in male biased sex ratios for this predator.

PMID- 11587624
TI  - Assessing mating performance of male Glossina pallidipes (Diptera: Glossinidae)
      using a walk-in field cage.
AB  - To monitor the quality of male tsetse for use in the sterile insect technique
      (SIT), a field cage test was developed and evaluated. Mating competitiveness was
      tested with male Glossina pallidipes Austen that emerged from pupae stored for
      different periods at 15 degrees C. Control males emerged from pupae stored at 23
      24 degrees C and emerged at 26.5 degrees C. Each sample of test males was divided
      into two groups with one group being irradiated at 120 Gy; the other group was
      not irradiated. More than 70% of the maximum possible number of mating pairs
      occurred in all tests. Males emerged from pupae kept at low temperature and then
      irradiated formed a greater proportion of mating pairs than the controls. Males
      emerged from pupae kept at 15 degrees C generally started mating more quickly
      than the standard colony males although there was no significant difference.
      Insemination rates were above 99%. Pooled data indicated that mean spermathecal
      values for females mated with irradiated males were significantly lower than for
      control males. The duration of copulation varied significantly between treatment
      groups and was significantly longer for irradiated male flies; there was no
      correlation between duration of copulation and mean spermathecal value.

PMID- 11587625
TI  - Differential behaviour of Anopheles gambiae sensu stricto (Diptera: Culicidae) to
      human and cow odours in the laboratory.
AB  - A dual port olfactometer was used to study the response of Anopheles gambiae
      Giles sensu stricto to odours of human and animal origin. Human odour consisted
      of human skin emanations collected on a nylon stocking, which was worn for 24 h.
      This was tested alone or together with 4.5% carbon dioxide, the concentration in
      human and cattle breath. Cattle odours consisted of cow skin emanations and/or
      carbon dioxide. Cow skin emanations were collected by tying a nylon stocking
      ('cow sock') around the hind leg of a cow for 12 h. Anopheles gambiae s.s. was
      consistently highly attracted by human odour, which is consistent with the high
      degree of anthropophily in this mosquito. Anopheles gambiae s.s. was not
      attracted by human or cattle equivalent volumes of carbon dioxide and this gas
      did not enhance the effect of human skin residues. Furthermore, A. gambiae s.s.
      showed a high degree of aversion to cow odour. When human odour and cow odour
      were tested together in the same port, mosquitoes were still highly attracted,
      indicating that whilst cattle odour may deter A. gambiae s.s., these mosquitoes
      can detect human odour in the presence of cattle odour. It was concluded that
      carbon dioxide plays a minor role in the host seeking behaviour of A. gambiae
      s.s., whilst host specific cues such as human skin residues play a major role and
      very effectively demonstrated anthropophilic behaviour in the laboratory.

PMID- 11587626
TI  - A shoot-fly Atherigona tritici sp. n. (Diptera: Muscidae), attacking wheat
      Triticum aestivum in Egypt.
AB  - The two 'forms' of the Afrotropical shoot-fly Atherigona rubricornis Stein are
      shown to be good species. A neotype is designated for the true A. rubricornis,
      which is restricted to tropical Africa. The other form is described as A. tritici
      sp. n. It is widespread in tropical Africa, but is known also from Egypt, where
      the larvae attack wheat seedlings, Israel and Yemen. Infestation levels of
      larvae, with maxima between 9% and 32%, indicate that it is a significant pest of
      wheat seedlings in Egypt.

PMID- 11587627
TI  - The effect of natural enemies on the spread of barley yellow dwarf virus (BYDV)
      by Rhopalosiphum padi (Hemiptera: Aphididae).
AB  - The effects of two natural aphid enemies, adult Coccinella septempunctata
      Linneaus, a predator, and Aphidius rhopalosiphi de Stefani Perez, a parasitoid,
      on spread of barley yellow dwarf virus (BYDV) transmitted by the bird cherry-oat
      aphid, Rhopalosiphum padi (Linnaeus) were studied under laboratory conditions.
      Predators or parasitoids were introduced to trays of durum wheat seedlings and
      the patterns of virus infection were observed after two, seven and 14 days of
      exposure. More plants were infected with BYDV in control trays without A.
      rhopalosiphi than in trays with the parasitoid present, both seven and 14 days
      after the introduction of parasitoids. Patterns of virus infection were found to
      be similar over time in trays with a parasitoid present and in control trays.
      More plants were infected in trays with C. septempunctata present than in control
      trays, both two and seven days after the introduction of the coccinellid. The
      spread of virus infections progressed differently over time for the two
      treatments (predator and parasitoid), differences between treatments being most
      marked after two days and seven days, when more plants exposed to predators but
      fewer exposed to parasitoids were infected with BYDV compared to their respective
      controls. However, by the 14th day 88% of all plants were infected and there was
      no significant difference between the two treatments. The role of natural enemies
      in spread of BYDV is discussed.

PMID- 11587628
TI  - Population dynamics of the white wax scale, Ceroplastes destructor (Hemiptera:
      Coccidae), on citrus in South Africa, with implications for biological control.
AB  - The population dynamics of the white wax scale, Ceroplastes destructor Newstead,
      was studied intensively in four easy-peel citrus orchards in the Western Cape
      Province of South Africa over three consecutive years (1997-1999). Key factor
      analysis was used to determine and quantify the contribution of individual
      mortality factors to the total generation mortality. Key stage mortality,
      determined from a cohort life table, was in the third instar and pre-ovipositing
      female stages. Mortality of C. destructor was caused primarily by parasitoids,
      predators and miscellaneous factors. Parasitoids and miscellaneous factors acted
      as density-dependent regulatory agents during the pre-ovipositional and first
      instar stages respectively. This has implications for biological control of C.
      destructor. Some of the mortality factors acted either randomly with no reference
      to the population densities or in an inverse density-dependent manner during the
      egg-crawler, second or third instar stages.

PMID- 11587629
TI  - Designing an AIDS vaccine.

PMID- 11587630
TI  - Burkitt's/Burkitt's-like lymphoma presenting as bacterial sinusitis in two HIV
      infected children.
AB  - Two children (ages 12 and 13 years) with transfusion-acquired human
      immunodeficiency virus (HIV) infection presented with facial pain and rhinorrhea.
      Radiographic imaging showed extensive paranasal sinus disease, presumed to be
      bacterial sinusitis, and the patients were treated with broad-spectrum oral
      antibiotics. Both patients were unresponsive to oral agents and were switched to
      intravenous antibiotics. Despite aggressive antimicrobial therapy, one patient
      (case 1) developed increased periorbital swelling and proptosis, and the other
      patient (case 2) developed symptoms of nasopharyngeal obstruction. Repeat imaging
      showed progression of the infiltrative process extending from the paranasal
      sinuses into the orbit (case 1), and nasopharynx (case 2). Surgical exploration
      and tissue biopsies were performed on both patients and the histopathology was
      consistent with Burkitt's/Burkitt's-like lymphoma. Combination systemic and
      intrathecal chemotherapy resulted in a complete remission in both patients. These
      reports illustrate the fact that Burkitt's/Burkitt's-like lymphoma in the
      paranasal sinuses may initially masquerade as an acute bacterial sinusitis. The
      ability of the tumor to extend rapidly from the sinuses into the orbit and
      nasopharynx reinforces the importance of early diagnosis and treatment.
      Burkitt's/Burkitt's-like lymphoma in the paranasal sinuses has not been
      previously described in HIV-infected children.

PMID- 11587631
TI  - Cytomegalovirus disease in the lower female genital tract.
AB  - Cytomegalovirus (CMV) can cause life-threatening disease in immunocompromised
      patients, such as those with human immunodeficiency virus (HIV). It is a rare but
      important cause of ulceration in the female genital tract. We report on three
      cases of CMV disease in the female genital tract. One patient presented with
      vulvar ulceration and fevers, and two patients presented with bleeding cervical
      lesions. All diagnoses were confirmed by histology. All patients were treated
      with intravenous ganciclovir with good result. CMV disease of the female genital
      tract may result in significant morbidity, with fever, pain, bleeding, and
      superinfection, and it may be associated with the development of pelvic
      inflammatory disease and cervical intraepithelial neoplasia. There are several
      options for diagnosis and for safe treatment.

PMID- 11587632
TI  - Comparison of AIDS progression and survival in persons with pulmonary versus
      extrapulmonary tuberculosis in Los Angeles.
AB  - The objective of this research was to compare the demographics, acquired immune
      deficiency syndrome (AIDS) progression, and survival in persons with AIDS with
      pulmonary tuberculosis (PTB) versus extrapulmonary tuberculosis (EPTB), because
      there are limited population-based data on this topic. A population-based
      longitudinal study with 3 years of follow-up was performed. Data were collected
      every 6 months from medical records of persons with AIDS and TB treated at
      private and public medical facilities throughout Los Angeles County (LAC).
      Participants included a population-based sample of 216 persons with AIDS and PTB
      and 166 persons with AIDS and EPTB (including 113 persons with both PTB and
      EPTB), with an AIDS diagnosis reported in 1993. Compared to persons with AIDS
      with PTB, persons with AIDS and EPTB were 2.2 times more likely to be Latino than
      white (95% confidence intervals [CIs]: 1.2, 4.0) and 1.7 times more likely to be
      foreign-born (95% CIs: 1.1, 2.5). Compared to persons with AIDS with PTB, persons
      with AIDS and EPTB had similar antiretroviral and PCP prophylaxis use; lower CD4
      counts at time of AIDS diagnosis (p = 0.0004); no differences in CD4 counts over
      the total follow-up period (p = 0.4); higher rates of total opportunistic
      infections (OIs) (incidence density ratio [IDR] = 2.0; 95% CIs: 1.6, 2.4); and
      comparable survival curves (p = 0.07). Persons with AIDS and EPTB had a more
      complicated medical course with lower CD4 counts at time of AIDS diagnosis and
      more OIs over the follow-up period than persons with AIDS and PTB, however the
      survival profiles for the two groups were comparable.

PMID- 11587633
TI  - Highly active antiretroviral therapy associated with improved anemia among HIV
      infected women.
AB  - Anemia is common during human immunodeficiency virus (HIV) infection and is
      associated with increased mortality. We conducted a study to examine the impact
      of highly active antiretroviral therapy (HAART) on anemia in a multicenter cohort
      of HIV-positive women, the Human Immunodeficiency Virus Epidemiology Research
      (HER) Study. Among women receiving HAART (n = 188), non-HAART monotherapy or
      combination antiretroviral therapy (ART) (n = 111), or who had no reported
      treatment (n = 62), the prevalence of anemia (hemoglobin, <120 g/L) at baseline
      was 38.3, 36.9, and 43.6%, respectively (p = 0.58) and at 1-year follow-up was
      26.1%, 36.9%, 45.2%, respectively (p = 0.01); mean hemoglobin at baseline was 125
      +/- 16, 122 +/- 16, and 122 +/- 18 g/L, respectively (p = 0.29) and at 1-year
      follow-up was 128 +/- 14, 123 +/- 16, and 119 +/- 20 g/L, respectively (p <
      0.0001). Adjusted linear regression models showed that HAART was associated with
      an increase of hemoglobin of 0.20 g/L per month (p = 0.007). After 1 year of
      treatment, HAART was associated with a 32% reduction in anemia among HIV-infected
      women (p = 0.01), whereas there was no significant change in the prevalence of
      anemia among those on non-HAART ART or those who had no reported treatment. HAART
      is associated with a large reduction in anemia among HIV-infected women.

PMID- 11587634
TI  - Quality of life and risk perception among predominantly heterosexual, minority
      individuals with HIV/AIDS.
AB  - The objective of this study was to examine the quality-of-life concerns of human
      immunodeficiency virus (HIV)-infected individuals and to assess their perceptions
      of acquired immune deficiency syndrome (AIDS) and the need for safer sex, in
      light of treatment advances. Respondents were recruited from seven AIDS service
      organizations in New York City, and the total sample consisted of 196 HIV
      infected individuals. The sample consisted largely of heterosexual, African
      Americans, and Latinos. Respondents completed a self-administered questionnaire
      that was made available in English or Spanish. Three-quarters of the sample were
      receiving protease inhibitor combination therapies. Overall, respondents reported
      a high level of life satisfaction as well as trust in their medical providers.
      Health worries and financial worries were the main areas of concern. A
      significant minority of respondents indicated reduced concern about AIDS and the
      need for continued safer sex practices, because of the latest treatments.
      Respondents with greater quality-of-life concerns were more likely to believe
      that AIDS was less severe now and that safer sex was less important.

PMID- 11587635
TI  - Adherence to highly active antiretroviral therapy in the real world: experience
      of twelve English HIV units.
AB  - In order to describe how human immunodeficiency virus (HIV) clinics in and around
      London are trying to optimize their patients' adherence to highly active
      antiretroviral therapy (HAART), we performed a survey of practice and policy in
      the clinics using a postal questionnaire. Clinics were also asked to review up to
      10 randomly selected case notes of patients receiving HAART and complete a
      questionnaire on each about how adherence was encouraged and assessed. Twelve
      clinics took part in the project and surveyed the notes of 89 patients. The
      results show that several clinics define adequate adherence as taking more than
      95% of prescribed doses although there was no uniform definition across the
      participating units. Adherence was encouraged through simplifying HAART regimens,
      providing dose-dispensing boxes and alarms, arranging early follow-up for
      patients starting treatment, and offering continuing support through specific
      health care workers. Adequate discussion and provision of written information was
      seen as an important aid to adherence but the case note survey showed evidence of
      deficiencies in this area in approximately 40% of patients. Assessed levels of
      adherence were less than 95% in 27% of patients. The main reasons for suboptimal
      adherence were found to be lack of motivation to take treatment by the patients,
      high pill burden, and drug side effects although there were several other
      contributing factors. This study shows that the HIV units take HAART adherence
      seriously but there are several deficiencies in putting policy into practice.

PMID- 11587636
TI  - Long-term response for nelfinavir.

PMID- 11587637
TI  - Newborn syphilis rates down.

PMID- 11587639
TI  - Crystal structure of paromomycin docked into the eubacterial ribosomal decoding A
      site.
AB  - BACKGROUND: Aminoglycoside antibiotics interfere with translation in both gram
      positive and gram-negative bacteria by binding to the tRNA decoding A site of the
      16S ribosomal RNA. RESULTS: Crystals of complexes between oligoribonucleotides
      incorporating the sequence of the ribosomal A site of Escherichia coli and the
      aminoglycoside paromomycin have been solved at 2.5 A resolution. Each RNA
      fragment contains two A sites inserted between Watson-Crick pairs. The
      paromomycin molecules interact in an enlarged deep groove created by two bulging
      and one unpaired adenines. In both sites, hydroxyl and ammonium side chains of
      the antibiotic form 13 direct hydrogen bonds to bases and backbone atoms of the A
      site. In the best-defined site, 8 water molecules mediate 12 other hydrogen bonds
      between the RNA and the antibiotics. Ring I of paromomycin stacks over base G1491
      and forms pseudo-Watson-Crick contacts with A1408. Both the hydroxyl group and
      one ammonium group of ring II form direct and water-mediated hydrogen bonds to
      the U1495oU1406 pair. The bulging conformation of the two adenines A1492 and
      A1493 is stabilized by hydrogen bonds between phosphate oxygens and atoms of
      rings I and II. The hydrophilic sites of the bulging A1492 and A1493 contact the
      shallow groove of G=C pairs in a symmetrical complex. CONCLUSIONS: Water
      molecules participate in the binding specificity by exploiting the antibiotic
      hydration shell and the typical RNA water hydration patterns. The observed
      contacts rationalize the protection, mutation, and resistance data. The crystal
      packing mimics the intermolecular contacts induced by aminoglycoside binding in
      the ribosome.

PMID- 11587640
TI  - Structure-based development of anticancer drugs: complexes of NAD(P)H:quinone
      oxidoreductase 1 with chemotherapeutic quinones.
AB  - BACKGROUND: NAD(P)H:quinone acceptor oxidoreductase (QR1) protects animal cells
      from the deleterious and carcinogenic effects of quinones and other
      electrophiles. Remarkably, the same enzyme activates cancer prodrugs that become
      cytotoxic only after two-electron reduction. QR1's ability to bioactivate
      quinones and its elevated expression in many human solid tumors makes this
      protein an excellent target for enzyme-directed drug development. Until now,
      structural analysis of the mode of binding of chemotherapeutic compounds to QR1
      was based on model building using the structures of complexes with simple
      substrates; no structure of complexes of QR1 with chemotherapeutic prodrugs had
      been reported. RESULTS: Here we report the high-resolution crystal structures of
      complexes of QR1 with three chemotherapeutic prodrugs: RH1, a water-soluble
      homolog of dimethylaziridinylbenzoquinone; EO9, an aziridinylindolequinone; and
      ARH019, another aziridinylindolequinone. The structures, determined to
      resolutions of 2.0 A, 2.5 A, and 1.86 A, respectively, were refined to R values
      below 21% with excellent geometry. CONCLUSIONS: The structures show that
      compounds can bind to QR1 in more than one orientation. Surprisingly, the two
      aziridinylindolequinones bind to the enzyme in different orientations. The
      results presented here reveal two new factors that must be taken into account in
      the design of prodrugs targeted for activation by QR1: the enzyme binding site is
      highly plastic and changes to accommodate binding of different substrates, and
      homologous drugs with different substituents may bind to QR1 in different
      orientations. These structural insights provide important clues for the
      optimization of chemotherapeutic compounds that utilize this reductive
      bioactivation pathway.

PMID- 11587641
TI  - X-ray crystal structure of proto-oncogene product c-Rel bound to the CD28
      response element of IL-2.
AB  - BACKGROUND: The proto-oncogene product c-Rel is a Rel/NF-kappaB family
      transcription factor that plays a critical role in lymphoid cell development and
      mediates CD28-induced expression of interleukin 2 (IL-2). The CD28 response
      element (CD28RE) in the IL-2 enhancer is nonameric and similar to the kappaB DNA
      target sites recognized by p65 homodimers. RESULTS: We have determined and
      refined the X-ray crystal structure of the c-Rel homodimer complexed to the
      CD28RE DNA site, 5'-AGAAATTCC-3', to 2.85 A resolution. The c-Rel homodimer binds
      CD28RE in a mode similar to that observed in the p65/IL-8 kappaB crystallographic
      complex. Binding studies reveal that the c-Rel homodimer recognizes the CD28RE
      with higher affinity as compared to other canonical kappaB sequences despite the
      nonconsensus A:T base pair at the 5' end of the CD28RE. Preferential recognition
      of the CD28RE by c-Rel results from the direct contacts between the protein and
      the DNA as well as intrasubunit interactions between the beta(f)-beta(g) loop in
      the dimerization domain and the DNA-contacting loop L1 of the N-terminal domain.
      Not only do these loops have different conformations in other Rel/DNA
      crystallographic complexes, but they also contain two of the five oncogenic point
      mutations found in v-Rel. CONCLUSIONS: The current structure indicates that a non
      DNA-contacting loop in the dimerization domain and the DNA-contacting loop L1 may
      play critical roles in defining affinity and specificity. Two amino acid changes
      in these segments may account for the differential DNA binding by v-Rel as
      compared to that of c-Rel.

PMID- 11587642
TI  - Complex between Peptostreptococcus magnus protein L and a human antibody reveals
      structural convergence in the interaction modes of Fab binding proteins.
AB  - BACKGROUND: Peptostreptococcus magnus protein L (PpL) is a multidomain, bacterial
      surface protein whose presence correlates with virulence. It consists of up to
      five homologous immunoglobulin binding domains that interact with the variable
      (VL) regions of kappa light chains found on two thirds of mammalian antibodies.
      RESULTS: We refined the crystal structure of the complex between a human antibody
      Fab fragment (2A2) and a single PpL domain (61 residues) to 2.7 A. The asymmetric
      unit contains two Fab molecules sandwiching a single PpL domain, which contacts
      similar VL framework regions of two light chains via independent interfaces. The
      residues contacted on VL are remote from the hypervariable loops. One PpL-Vkappa
      interface agrees with previous biochemical data, while the second is novel. Site
      directed mutagenesis and analytical-centrifugation studies suggest that the two
      PpL binding sites have markedly different affinities for VL. The PpL residues in
      both interactions are well conserved among different Peptostreptococcus magnus
      strains. The Fab contact positions identified in the complex explain the high
      specificity of PpL for antibodies with kappa rather than lambda chains.
      CONCLUSIONS: The PpL-Fab complex shows the first interaction of a bacterial
      virulence factor with a Fab light chain outside the conventional combining site.
      Structural comparison with two other bacterial proteins interacting with the Fab
      heavy chain shows that PpL, structurally homologous to streptococcal SpG domains,
      shares with the latter a similar binding mode. These two bacterial surface
      proteins interact with their respective immunoglobulin regions through a similar
      beta zipper interaction.

PMID- 11587643
TI  - Crystal structure of maltose phosphorylase from Lactobacillus brevis: unexpected
      evolutionary relationship with glucoamylases.
AB  - BACKGROUND: Maltose phosphorylase (MP) is a dimeric enzyme that catalyzes the
      conversion of maltose and inorganic phosphate into beta-D-glucose-1-phosphate and
      glucose without requiring any cofactors, such as pyridoxal phosphate. The enzyme
      is part of operons that are involved in maltose/malto-oligosaccharide metabolism.
      Maltose phosphorylases have been classified in family 65 of the glycoside
      hydrolases. No structure is available for any member of this family. RESULTS: We
      report here the 2.15 A resolution crystal structure of the MP from Lactobacillus
      brevis in complex with the cosubstrate phosphate. This represents the first
      structure of a disaccharide phosphorylase. The structure consists of an N
      terminal complex beta sandwich domain, a helical linker, an (alpha/alpha)6 barrel
      catalytic domain, and a C-terminal beta sheet domain. The (alpha/alpha)6 barrel
      has an unexpected strong structural and functional analogy with the catalytic
      domain of glucoamylase from Aspergillus awamori. The only conserved glutamate of
      MP (Glu487) superposes onto the catalytic residue Glu179 of glucoamylase and
      likely represents the general acid catalyst. The phosphate ion is bound in a
      pocket facing the carboxylate of Glu487 and is ideally positioned for
      nucleophilic attack of the anomeric carbon atom. This site is occupied by the
      catalytic base carboxylate in glucoamylase. CONCLUSIONS: These observations
      strongly suggest that maltose phosphorylase has evolved from glucoamylase. MP has
      probably conserved one carboxylate group for acid catalysis and has exchanged the
      catalytic base for a phosphate binding pocket. The relative positions of the acid
      catalytic group and the bound phosphate are compatible with a direct-attack
      mechanism of a glycosidic bond by phosphate, in accordance with inversion of
      configuration at the anomeric carbon as observed for this enzyme.

PMID- 11587644
TI  - Structure of the PPARalpha and -gamma ligand binding domain in complex with AZ
      242; ligand selectivity and agonist activation in the PPAR family.
AB  - BACKGROUND: The peroxisome proliferator-activated receptors (PPAR) are ligand
      activated transcription factors belonging to the nuclear receptor family. The
      roles of PPARalpha in fatty acid oxidation and PPARgamma in adipocyte
      differentiation and lipid storage have been characterized extensively. PPARs are
      activated by fatty acids and eicosanoids and are also targets for
      antidyslipidemic drugs, but the molecular interactions governing ligand
      selectivity for specific subtypes are unclear due to the lack of a PPARalpha
      ligand binding domain structure. RESULTS: We have solved the crystal structure of
      the PPARalpha ligand binding domain (LBD) in complex with the combined PPARalpha
      and -gamma agonist AZ 242, a novel dihydro cinnamate derivative that is
      structurally different from thiazolidinediones. In addition, we present the
      crystal structure of the PPARgamma_LBD/AZ 242 complex and provide a rationale for
      ligand selectivity toward the PPARalpha and -gamma subtypes. Heteronuclear NMR
      data on PPARalpha in both the apo form and in complex with AZ 242 shows an
      overall stabilization of the LBD upon agonist binding. A comparison of the novel
      PPARalpha/AZ 242 complex with the PPARgamma/AZ 242 complex and previously solved
      PPARgamma structures reveals a conserved hydrogen bonding network between
      agonists and the AF2 helix. CONCLUSIONS: The complex of PPARalpha and PPARgamma
      with the dual specificity agonist AZ 242 highlights the conserved interactions
      required for receptor activation. Together with the NMR data, this suggests a
      general model for ligand activation in the PPAR family. A comparison of the
      ligand binding sites reveals a molecular explanation for subtype selectivity and
      provides a basis for rational drug design.

PMID- 11587645
TI  - Active transport of an antibiotic rifamycin derivative by the outer-membrane
      protein FhuA.
AB  - BACKGROUND: FhuA, an integral membrane protein of Escherichia coli, actively
      transports ferrichrome and the structurally related antibiotic albomycin across
      the outer membrane. The transport is coupled to the proton motive force, which
      energizes FhuA through the inner-membrane protein TonB. FhuA also transports the
      semisynthetic rifamycin derivative CGP 4832, although the chemical structure of
      this antibiotic differs markedly from that of ferric hydroxamates. RESULTS: X-ray
      crystallography revealed that rifamycin CGP 4832 occupies the same ligand binding
      site as ferrichrome and albomycin, thus demonstrating a surprising lack of
      selectivity. However, the binding of rifamycin CGP 4832 is deviant from the
      complexes of FhuA with hydroxamate-type ligands in that it does not result in the
      unwinding of the switch helix but only in its destabilization, as reflected by
      increased B factors. Unwinding of the switch helix is proposed to be required for
      efficient binding of TonB to FhuA and for coupling the proton motive force of the
      cytoplasmic membrane with energy-dependent ligand transport. The transport data
      from cells expressing mutant FhuA proteins indicated conserved structural and
      mechanistic requirements for the transport of both types of compounds.
      CONCLUSIONS: We conclude that the binding of rifamycin CGP 4832 destabilizes the
      switch helix and promotes the formation of a transport-competent FhuA-TonB
      complex, albeit with lower efficiency than ferrichrome. Active transport of this
      rifamycin derivative explains the 200-fold increase in potency as compared to
      rifamycin, which is not a FhuA-specific ligand and permeates across the cell
      envelope by passive diffusion only.

PMID- 11587646
TI  - Beyond the "recognition code": structures of two Cys2His2 zinc finger/TATA box
      complexes.
AB  - BACKGROUND: Several methods have been developed for creating Cys2His2 zinc finger
      proteins that recognize novel DNA sequences, and these proteins may have
      important applications in biological research and gene therapy. In spite of this
      progress with design/selection methodology, fundamental questions remain about
      the principles that govern DNA recognition. One hypothesis suggests that
      recognition can be described by a simple set of rules--essentially a "recognition
      code"--but careful assessment of this proposal has been difficult because there
      have been few structural studies of selected zinc finger proteins. RESULTS: We
      report the high-resolution cocrystal structures of two zinc finger proteins that
      had been selected (as variants of Zif268) to recognize a eukaryotic TATA box
      sequence. The overall docking arrangement of the fingers within the major groove
      of the DNA is similar to that observed in the Zif268 complex. Nevertheless,
      comparison of Zif268 and the selected variants reveal significant differences in
      the pattern of side chain-base interactions. The new structures also reveal side
      chain-side chain interactions (both within and between fingers) that are
      important in stabilizing the protein-DNA interface and appear to play substantial
      roles in recognition. CONCLUSIONS: These new structures highlight the surprising
      complexity of zinc finger-DNA interactions. The diversity of interactions
      observed at the protein-DNA interface, which is especially striking for proteins
      that were all derived from Zif268, challenges fundamental concepts about zinc
      finger-DNA recognition and underscores the difficulty in developing any
      meaningful recognition code.

PMID- 11587647
TI  - Crystal structure of manganese catalase from Lactobacillus plantarum.
AB  - BACKGROUND: Catalases are important antioxidant metalloenzymes that catalyze
      disproportionation of hydrogen peroxide, forming dioxygen and water. Two families
      of catalases are known, one having a heme cofactor, and the other, a structurally
      distinct family containing nonheme manganese. We have solved the structure of the
      mesophilic manganese catalase from Lactobacillus plantarum and its azide
      inhibited complex. RESULTS: The crystal structure of the native enzyme has been
      solved at 1.8 A resolution by molecular replacement, and the azide complex of the
      native protein has been solved at 1.4 A resolution. The hexameric structure of
      the holoenzyme is stabilized by extensive intersubunit contacts, including a beta
      zipper and a structural calcium ion crosslinking neighboring subunits. Each
      subunit contains a dimanganese active site, accessed by a single substrate
      channel lined by charged residues. The manganese ions are linked by a mu1,3
      bridging glutamate carboxylate and two mu-bridging solvent oxygens that
      electronically couple the metal centers. The active site region includes two
      residues (Arg147 and Glu178) that appear to be unique to the Lactobacillus
      plantarum catalase. CONCLUSIONS: A comparison of L. plantarum and T. thermophilus
      catalase structures reveals the existence of two distinct structural classes,
      differing in monomer design and the organization of their active sites, within
      the manganese catalase family. These differences have important implications for
      catalysis and may reflect distinct biological functions for the two enzymes, with
      the L. plantarum enzyme serving as a catalase, while the T. thermophilus enzyme
      may function as a catalase/peroxidase.

PMID- 11587649
TI  - [Dementia and falls].
AB  - INTRODUCTION: Dementia is now a frequent disease in elderly and may be a major
      risk of falling. Usually these falls are multiple and serious, but their
      consequences are not specific. All types of dementia (Alzheimer's disease,
      dementia with Lewy bodies, dementia in Parkinson's disease, fronto-temporal
      dementia, vascular dementiaellipsis) and all stages of evolution are concerned.
      DISCUSSION: These falls result from cognitive and behavioural disorders, visual
      and motor problems, gait and balance disturbances, malnutrition, adverse effects
      of medication and fear of falling. CONCLUSION: Prevention is possible. Attention
      must be given on the patient himself (keeping in good health, limitation in
      sedative treatment and mechanical restraintsellipsis) and on his environment
      (lighting, obstacles on the ground, stress levelellipsis). After a fall,
      especially after a complicated fall, rehabilitation modalities and aims must be
      adapted but caring must not be defeatist. Randomized studies need to be realized.

PMID- 11587648
TI  - Structural basis for allosteric substrate specificity regulation in anaerobic
      ribonucleotide reductases.
AB  - BACKGROUND: The specificity of ribonucleotide reductases (RNRs) toward their four
      substrates is governed by the binding of deoxyribonucleoside triphosphates
      (dNTPs) to the allosteric specificity site. Similar patterns in the kinetics of
      allosteric regulation have been a strong argument for a common evolutionary
      origin of the three otherwise widely divergent RNR classes. Recent structural
      information settled the case for divergent evolution; however, the structural
      basis for transmission of the allosteric signal is currently poorly understood. A
      comparative study of the conformational effects of the binding of different
      effectors has not yet been possible; in addition, only one RNR class has been
      studied. RESULTS: Our presentation of the structures of a class III anaerobic RNR
      in complex with four dNTPs allows a full comparison of the protein conformations.
      Discrimination among the effectors is achieved by two side chains, Gln-114 and
      Glu-181, from separate monomers. Large conformational changes in the active site
      (loop 2), in particular Phe-194, are induced by effector binding. The
      conformational differences observed in the protein when the purine effectors are
      compared with the pyrimidine effectors are large, while the differences observed
      within the purine group itself are more subtle. CONCLUSIONS: The subtle
      differences in base size and hydrogen bonding pattern at the effector site are
      communicated to major conformational changes in the active site. We propose that
      the altered overlap of Phe-194 with the substrate base governs hydrogen bonding
      patterns with main and side chain hydrogen bonding groups in the active site. The
      relevance for evolution is discussed.

PMID- 11587650
TI  - [Classification and mechanisms of body perceptions in the amputees].
AB  - OBJECTIVE: Amputees can experience several types of physical illusions and
      phantom limb phenomenon. The objective was to establish a synthetic
      classification of theses perceptions. METHOD: Prospective study in 75 amputees
      (group 1: amputation (n = 60), group 2: congenital defect). The subjects were
      asked first to report their perceptions spontaneously and then to detail the
      perception, if exist, of the missing limb: form recognition, posture, movement,
      reminiscence of a lost limb. RESULTS: Different types of perception were
      described besides the perception of the real state : normal, deformed or
      commemorative phantom limb and illusion of a normal body. DISCUSSION: Whatever
      the model (i.e.: neuro-matrix) which support the construction of the scheme and
      the body image, the representations related to identified perceptions, use
      various innate, autobiographic and identity frames of references as well as
      instantaneous peripheral information, treated by reorganized cerebral structures.
      Each type of perception is related to a particular representation pattern.
      CONCLUSION: This approach, in accordance with the literature, offers a better
      understanding of the differences between amelic and amputated subjects and of
      their perception of any prosthetic equipment.

PMID- 11587651
TI  - [Post-traumatic endocrine deficits : analysis of a series of 93 severe traumatic
      brain injuries].
AB  - OBJECTIVE: The aim of the study is to measure the incidence in severe traumatic
      brain injury of endocrine deficits with special consideration for
      hypotestosteronemia in male patients. PATIENTS AND METHODS: Retrospective
      analysis of a series of 115 TBIs consecutively admitted to our brain injury unit.
      Endocrine screening is routinely performed at admission and includes
      radioimmunological assays for T3, T4, TSH, testosterone or oestradiol and
      progesterone, FSH, LH and cortisol. Twenty-two records were incomplete and
      excluded from further analysis. The analysis relies on 93 records among which
      those of 75 males. RESULTS: One partial hypothyroidism of pituitary origin (low
      T3, T4 and TSH and no raise of TSH after stimulation by TRH) and one
      posthypophyseal deficit were found. The incidence of hypotestosteronemia is 28%.
      All are of central origin (low testosterone and low or normal LH). In one case
      the hypothalamic origin is demonstrated by the considerable increase of LH after
      injection of GnRH. We found no correlation between the occurrence of endocrine
      deficit and either the Glasgow Coma Scale or the existence of basal skull
      fracture. DISCUSSION - CONCLUSION: These results show that endocrine deficits are
      not exceptional in TBIs and that isolated hypotestosteronemia is frequent. These
      deficits are not necessarily all of functional origin, but further studies
      including longitudinal follow up are required to conclude on this point. Further
      studies addressing the opportunity of substitution in some patients should also
      be conducted.

PMID- 11587652
TI  - [Spasticity and dynamic plantar pressure distribution measurements in hemiplegic
      spastic children].
AB  - OBJECTIVE: The aim of this study was to analyse the plantar pressure distribution
      in nine hemiplegic spastic children to illustrate the dynamic alteration during
      stance phase linked spasticity grade. MATERIAL AND METHODS: The graduation of the
      lower limbs muscle tone related to the Aschworth spasticity scale enabled us to
      identify two groups of hemiplegics subjects. The groups Asch 1 and Asch 3 have
      respectively presented a low and a strong spasticity. The peak pressures during
      consecutive gait cycles were determined under the feet of 30 healthy subjects and
      two cerebral palsy groups using a wearable footprint analysis system. RESULTS: A
      statistical study showed a similarity between the two disabled groups. Peak
      pressures under the midfoot were significantly higher compared to the control
      group. While the plantar pressure distribution profile was specific for each
      group under all other anatomical structures. The significant alterations were
      observed under the forefoot and hallux. DISCUSSION-CONCLUSION: Spasticity
      modifies the foot contact to ground and leads to a specific plantar pressure
      distribution profile linked to the spasticity grade. The equinovarus with clawed
      toes deformity due to higher spasticity seems to be an important factor in
      terminal stance phase perturbations. However spastic hemiplegic subjects seem to
      adopt a gait pattern in agreement with stability optimization criteria.

PMID- 11587654
TI  - [Physical therapy of frozen shoulder: literature review].
AB  - OBJECTIVE: To determine the efficacy of physical treatments in adhesive
      capsulitis of the shoulder by a systematic review of literature, attempting to
      perform a meta-analysis from randomised clinical trials. METHOD: A systematic
      literature search was conducted to retrieve all randomised controlled trials of
      physical therapy such as physiotherapy and manipulation, but also arthrographic
      distension, mobilisation under general anaesthesia or nerve block, arthroscopic
      distension or arthrolysis, and intra-articular corticoid injections. The main
      outcome for meta-analysis was the restoration of range of movement between the
      sixth week and the third month. RESULTS: Only 16 articles could be selected, and
      only three about capsular distension were included in a meta-analysis because of
      the heterogeneity of the criteria assessing the functional results and of the
      poor methodological value of most of the articles. DISCUSSION: Some open studies
      stressed the value of daily manipulations and physiotherapy, intra-articular
      corticosteroid injections, but their quality was poor or limited. Nothing was
      written about antalgic drugs to facilitate joint mobilisation, and the use of a
      thoraco-brachial abduction device between exercises was only quoted. The most
      refractory cases might need more aggressive interventions: arthrographic
      distension with local anaesthesia and steroid injection; mobilisation under
      general or local anaesthesia, specially interscalene brachial plexus block;
      arthroscopic release. But there was no randomised controlled study comparing
      these three techniques and it seemed impossible to come to any conclusion about
      the superiority of one of them. The meta-analysis showed yet that capsular
      distension with intra-articular corticoid injections was better than corticoid
      injections alone. CONCLUSION: This demonstrated the need of a consensus about the
      criteria of assessment, the time of evaluation, before assessing by randomised
      clinical trials of good quality their therapeutic value.

PMID- 11587653
TI  - [Intracavernous injections in the treatment of erectile dysfunction in spinal
      cord injured patients: experience with 36 patients].
AB  - OBJECTIVES: To confirm the efficiency of intracavernous injections in the
      treatment of erectile dysfunction in spinal cord injured (SCI) patients and to
      determine the mean necessary dose to obtain functional erection. MATERIALS: This
      prospective study concerns 36 spinal cord injured men. None of them had erectile
      dysfunction before the neurologic impairement. Sixty four intracavernous
      injections were performed. METHOD: The first injection was done with the usually
      recommended starting dose. The injections were then repeated with increasing
      dosage to archive a rigid erection. The erection was evaluated with Schramek
      grading. A grade 4 or 5 erection was considered as functional. RESULTS: Nine
      tetraplegics and 27 paraplegics were included. Twenty two were grade A in ASIA
      classification. The mean age was 31 years. Twenty for patients had a level above
      T10, 11 between T11 and L2, one below L2. Twenty seven patients obtained an
      erection of grade 4 or 5. Alprostadil was used 51 times, moxisylite nine times
      and papaverine four times. The average dose necessary to obtain a grade 4 or 5
      functional erection adequate for coitus was 12.3 +/- 4.8 microgram with
      alprostadil and 14 +/- 5.4 mg with moxisylite. No side effects were noted. The
      nine left patients did not archive satisfying erection during this study. No
      clinical differences were noted in this population, compared with the 27 other
      patients. CONCLUSION: The findings confirm the efficiency of intracavernous
      injections in the management of erectile dysfunction in SCI. The average doses
      required to obtain a functional erection was 12.3 (+/- 4.8) microgram with
      alprostadil and 14 (+/- 5.4) mg with moxisylyte.

PMID- 11587655
TI  - [Musculoskeletal disorders in instrumental musicians: epidemiological study].
AB  - OBJECTIVES: To evaluate the frequency and types of musculoskeletal problems of
      French instrumental musicians. METHODS: Voluntary musicians answered an anonymous
      questionnaire about their musical practices, their medical history, and the
      evaluation of the troubles they feel during playing music. The musicians have
      been contacted in music schools, professional and not-professional orchestras.
      RESULTS: During this study 635 musicians received a questionnaire. 141 answered
      it (22.5%): 76.6% suffer from overuse syndrome, 17% from entrapment neuropathies,
      5.7% from occupational hand cramp. The main topographies are spine (60.9%) and
      wrist and hand (52.5%). Instrumental characteristics are exposed. CONCLUSION:
      Instrumental musicians often present musculoskeletal problems. A specific
      management would be useful to limit eventual drammatical consequences.

PMID- 11587656
TI  - [Influence of a typical "posture-balance-motivity" motor practice on the postural
      capacities of elderly subjects].
AB  - OBJECTIVE: The object of this work was to observe the influence of the "Posture
      Balance-Motivity" (PBM) activity on the total motivity in older adults. SUBJECTS
      AND METHOD: After 12 weeks of practice, to observe the effects on the control of
      static postural sway by the intermediary of a force platform of 15 subjects (mean
      age 75.5, SD = 6.6). RESULTS: Scores on "Posture", "Balance" and "Motivity" show
      respectively and significantly improvements. All scores of a clinical balance
      assessment scale, the POMA, have also improved. On the platform, parameters of
      spontaneous postural sway in the lateral (X) and antero-posterior (Y) axis have
      been evaluated with eyes open, eyes closed, on firm floor and foam floor
      condition. Values on the lateral axis did not show any significant decrease. But
      values on the antero-posterior axis showed a significant decrease for all
      modalities translating a better postural stability in this plan. CONCLUSION:
      These first results show the advantages of a typical "PBM" activity.

PMID- 11587657
TI  - [Professional outcome of reflex sympathetic dystrophy].
AB  - OBJECTIVE: In spite of physical medicine and rehabilitation care, post-traumatic
      reflex sympathetic dystrophy can be at the origin of articular deficiency, which
      decrease the capacity to return to work. The aim of this study is to know the
      professional future of patients who present post-traumatic reflex sympathetic
      dystrophy. MATERIAL AND METHOD: Eighteen months prospective study, carried out
      from patients in age to work, hospitalized in physical medicine and
      rehabilitation unit for osteo-articular traumatism complicated by reflex
      sympathetic dystrophy. Description of the population and comorbidity factors
      preventing professional resumption. Determination of the duration of medical
      certificate and the modalities of professional resumption. RESULTS: From 16
      patients in age to work, only 12 were able to resume a full time profession with
      an average period of 10.5 months +/- 5. The importance of the, the distale
      articular location of reflex sympathetic dystrophy (wrist - hand, ankle - foot),
      the association with a comorbidity such as chronic alcoholism represent
      pejorative factors of working resumption. Organizations of workstation are often
      necessary in six cases over eight, if the job is not sedentary. In the most
      complicated cases, inaptitudes in the work are pronounced with demand of
      professional reclassifying. CONCLUSION: Post-traumatic reflex sympathetic
      dystrophy represents a real challenge for the rehabilitation team, to minimize
      deficiencies and to help the patient to become again a worker.

PMID- 11587658
TI  - [Recurrent rhabdomyolysis revealing chronic exertional compartment syndrome of
      the biceps].
AB  - OBJECTIVE AND PATIENT: To report, an uncommon case of recurrent effort-related
      biceps compartment syndrome induced by strengthening exercises (body building) in
      a thirty-years-old white man. DISCUSSION-CONCLUSION: compartment syndrome is
      typically observed in the lower leg or in the forearm with pain, muscle
      tightness, cramp-like feeling during exertion. The involvement of the biceps was
      only described after traumatisms. Patient was initially thought to have metabolic
      myopathy because acute episodes of exercise induced myalgia and elevated serum
      CK. Tissue pressure monitoring prior and after a standard exercise test is
      helpful for diagnosing the recurrent form. The only alternative to fasciotomy is
      to stop sports activities.

PMID- 11587659
TI  - [Rhizarthrosis and orthotic treatment. Review of literature].
AB  - OBJECTIVES: Trapeziometacarpal arthritis or rhizarthrosis is extremely frequent.
      Numerous treatments are available including drugs, physiotherapy, use of orthotic
      devices, surgery, etc. Few of these methods have been really evaluated. We
      propose a critical review of the literature on orthotic treatment in
      rhizarthrosis. MATERIALS AND METHODS: Review of the results of hand splint used
      in rhizarthrosis from eight studies published over the last ten years. RESULTS:
      Resting hand splints offer lasting and significant pain relief with a
      satisfactory compliance. They should be applied early in treatment and evaluated
      with regular follow-up. The drop-out rate is about 10%. Working hand splints,
      either alone or associated with a resting splint are also efficient. These is no
      modification in either the force or the ranges of motion. The functional benefit
      is satisfactory if the follow-up allows some tolerance and thus an optimal
      compliance. CONCLUSION: The major interest of the use of splinting is analgesia.
      The pain releif obtained with splint is similar when used alone or with a working
      hand splint. Working hand splint can improve hand function during vocational and
      avocational activities.

PMID- 11587660
TI  - [French translation and validation of a functional disability scale for neck
      pain].
AB  - OBJECTIVES: To translate and to assess the reliability and the construct validity
      of the French translation of the Neck Pain and Disability Scale (NPDS), an
      American functional disability scale for neck pain. PATIENTS AND METHODS: Non
      randomised prospective study, where patients with neck disorders were included.
      Impairment outcomes measures (VAS Pain, range of motion of neck, score of neck
      sensitivity, radiologic score of Kellgren) and patientsperceived handicap (VAS)
      were recorded at the baseline visit. Disability was assessed with the NPDS, that
      was recorded twice, at baseline visit and 24 hours later. Reliability was
      assessed using the intraclass correlation coefficient (ICC) and the Bland and
      Altman method. Construct (convergent and divergent) validity was investigated
      using the Spearman rank correlation coefficient and a factor analysis was
      performed. RESULTS: One hundred and one patients were included. French versions
      were obtained using the "translation/backward translation" method. Expected
      convergent (r = 0.51 with VAS Pain, 0.63 with VAS Functional Disability, 0.67
      with VAS Handicap) and divergent (r = 0.39 and 0.49 respectively for the anxiety
      and depression scores of HAD, palpation sensitivity r = 0.31, neck mobility r = -
      0.45 and 0.28, and Kellgrens radiologic score r = 0.04) validity were observed,
      suggested good construct validity. Test-retest was excellent for NPDS with ICC =
      0.91. The Bland and Altman method showed distribution of differences homogenous
      and no systematic trend. Three mains factors were extracted by factors analysis
      of the NPDS, and explained 78% of the cumulative variance. CONCLUSION: The French
      version of NPDS has good metrologic qualities. This scale can be used in clinical
      practice to assess disability in neck pain and to normalise disability
      assessment.

PMID- 11587661
TI  - [Reliability of TcPO(2) measurement in the upper limb].
AB  - INTRODUCTION: Several reports suggest the usefulness of transcutaneous oxygen
      tension (TcPO(2)) in assessing the shoulder hand syndrome in stroke patients. But
      the literature presents a number of conflicting views on the variation of TcPO(2)
      values in this case. We found no report demonstrating the reliability of TcPO(2)
      measurements in the upper limb. The aim of this study was to evaluate the
      reliability of TcPO(2) measurements and investigate whether TcPO(2) can be used
      to evaluate the shoulder hand syndrome after stroke. MATERIAL AND METHODS: The
      TcPO(2) values were obtained on two separate occasions at one-day interval on 18
      normal volunteers. Basal TcPO(2), local vasomotor reflex and reaction to ischemia
      were assessed. RESULTS: Thirty-six upper limbs were tested. The reliability was
      bad. We found that measurements of TcPO(2) varied by an average of 7.89 +/- 7.6
      mmHg for a coefficient of variation of 96%. CONCLUSION: The reliability of
      TcPO(2) measurement was not sufficient to recommend this method in this
      indication.

PMID- 11587662
TI  - [Belated diagnosis of medullar compression in a case of post-polio syndrome].
AB  - The physiatrist observes about his practice individuals with sequela of old
      poliomyelitics. A part of them have unusual fatigue and muscular pains and
      weakness. The hypothesis of an evolution of neuro-biological mechanism suggested
      by few authors isn't, actually, demonstrated. More probably, the modifications of
      lesional and, functional changes with disability observed are the consequence of
      elderly effects and decreasing of physical activites. We report a case of spinal
      cord compression by intramedullar tumor, associated with a post-polio syndrome.

PMID- 11587663
TI  - [Physical medicine and rehabilitation. Where did it come from? Where is it
      going?].

PMID- 11587664
TI  - [What is a "left"?].
AB  - OBJECTIVE: Patients with right hemisphere syndrome may be labeled as "gauche" by
      the rehabilitation staff. This term corresponds to a variety of oddities in
      behavior or discourse. The aim of this study is to understand the coherence of
      these oddities with the classical elements of right hemisphere syndrome.
      MATERIAL: In this article, we present a detailed study of the discourse and the
      relation with others of a patient with severe left hemineglect, who was followed
      up for twelve months and did not exhibited any significant change in his
      symptomatology. METHODS: This study relies on the data from neuropsychological
      examination, on notes written after rehabilitation session by the therapists and
      on data from weekly non-directive interviews. RESULTS: This follow-up revealed
      disturbances of time sense, reduplication for places, misidentification of
      therapists, pseudo hallucinations, and showed that the transferential relation
      was "floating". The non-directive interviews permitted the patient to express his
      own interpretation of his troubles. He described them in terms of gaps in his
      body "carapace" and disorganization of the oral drive. CONCLUSION: We propose to
      consider the symptomatology of this patient in relation with the subjective
      effects of the breaking up of his body image and the concomitant intrusion of the
      oral object (in the psychoanalytic sense of this term) in his psychic reality.

PMID- 11587665
TI  - [Validity and reliability of spinal clinical measures in ankylosing spondylitis].
AB  - OBJECTIVES: To evaluate the validity and the reliability of the main clinical
      measures of mobility and sagittal spinal curves in ankylosing spondylitis (AS).
      METHODS: Criterion validity of the measure of the distance between C7 spinous
      process to plumbline (dorsal kyphosis), L3-plumb line (lumbar lordosis), lumbar,
      dorsolumbar and dorsal mobility. The gold standard was the value obtained from
      lateral radiological views of the dorsal and lumbar spine in standing position
      and maximum flexion. The correlation between radiological and clinical measures
      was assessed by a Spearman correlation coefficient (SCC). The reliability was
      assessed for all the clinical parameters and for chin-sternum distance (flexion,
      extension), chin-acromion distance (rotations) and chest expansion using the
      intraclass correlation coefficient (ICC) and the Bland and Altman method. Were
      included patients with AS and needing dorsal and lumbar Xrays. RESULTS: Twenty
      two patients (21 men), 32 +/- 11 year old, 51 +/- 10 kg weight, with a mean
      duration of the disease of 120 +/- 60 months. The ICC values were good or
      excellent for all parameters except for the measures of dorsal mobility. The
      validity was evaluated in 18 patients. The value of the SCC between clinical and
      radiological measures was good except the measures of dorsal kyphosis and dorsal
      mobility. CONCLUSION: The clinical measures of mobility and sagittal curves have
      metrological properties good enough to be used in the monitoring of AS mainly for
      the follow-up and the evaluation of the rehabilitation. The measurement of dorsal
      mobility should be restricted to the lower part only. Although apparently not
      valid the distance C7-plumbline can be used in management of AS because of its
      excellent reliability.

PMID- 11587666
TI  - [Ulnar nerve tunnel syndrome of the elbow and an occupational disorder. Analysis
      of socio-professional and physical parameters].
AB  - PURPOSE: The ulnar nerve tunnel syndrome at the elbow is the second frequently
      tunnel syndrome, registered as an occupational disorder. The musculoskeletal
      troubles of the upper limb are now a public health challenge. These disorders
      allow manifold risk factors related to the work state, extrinsic to the patient,
      and related to individual factors, or intrinsic. MATERIAL AND METHOD: In the same
      venture, 25 patients with a UNTS, declared as an occupational disorder, have been
      compared to 48 individuals (T). Intrinsic (physical and psychological) and
      extrinsic parameters have been evaluated by a questionnaire, physical examination
      completed by an investigation in the venture. The Nottingham Health Profile was
      performed by all the individuals. RESULTS: All the cases of UNTS were observed
      after an increase of the production and a change in the work organization. Only
      50% of the declared UNTS have a typical topography of the pain. No UNTS patient
      had neurological objective motor and sensitive deficit. 52% of the UNTS patients
      had diffused physical disorders comparatively to 17% of the T population. Stress
      events were observed more frequently in the UNTS population than in the T
      population: in the living area, in respectively 96% and 52% of the cases, at the
      work place in 12% and 2%. 50% of the UNTS population was distress comparatively
      to 17% of the T population. The NHP score was significantly higher in the UNTS
      population than the T population. CONCLUSION: These data confirm the mutual
      influences of individual factors, physical and psychological, and of workplace
      factors in the occurrence of painful disorders related to an occupational
      activity. The therapeutic approach of these patients must be done with a
      physical, psychological and social evaluation.

PMID- 11587667
TI  - [Critical analysis of a systematic review of the literature and a meta-analysis
      on exercise therapy and chronic low back pain].
AB  - OBJECTIVES: To determine wether the type of quality assessment scale used for
      evaluating the role of the physical training in chronic low back pain affects the
      conclusions of meta-analytic studies. DESIGN AND SETTING: Analysis of 20 trials
      assessing exercise therapy in chronic low back pain using 16 different scales to
      identify high-quality trials. Correlations between the scale scores were assessed
      using the Spearmans rank correlation coefficient. Inter-reader reliability was
      assessed with the intraclass correlation coefficient (ICC) and with the Bland and
      Altman technique. For the quality assessment scales allowing the classification
      in high quality or low quality trials, the degree of agreement between the two
      readers was calculated using the kappa coefficient. RESULTS: The range of the
      Spearman rank correlation coefficients between the different quality scales was
      wide (from 0.94 to 0.49). The quality scales inter-reader reliability were
      heterogeneous, ICC ranging from 0.86 to 0.39. The Bland and Altman analysis
      showed that with two scales the differences were not centered and that with 3
      scales there was a systematic effect (r=0.32, 0.41, and 0.50). Finally, inter
      reader agreement was low most of the time, the K coefficient being less than or
      equal to 0.60 for 8 of the 12 quality scales tested. CONCLUSIONS: Our data
      suggest that the use of summary scores to identify trials of high quality is
      problematic. Relevant methodological aspects should be assessed more specifically
      based on treatment strategies than on the own disease. A large reflexion on the
      elaboration and validation of specific quality scales is needed.

PMID- 11587668
TI  - [Cartilage: from biomechanics to physical therapy].
AB  - OBJECTIVES: To review the current knowledge about the relationship between
      physical activities, cartilage biology, osteoarthritis and rehabilitation.
      METHOD: PubMed, Ovid, Cochrane Data base were interrogated for the period 1966
      2000. Key words were: chondrocyte, cartilage, osteoarthritis, mechanical
      stimulation, exercises, physical therapy, rehabilitation. Were reviewed: the
      mechanical biology of the chondrocytes and the cartilage, the mechanisms of
      transduction, the metabolic response of the chondrocytes to mechanical stresses;
      the effects of physical activity and immobilization on the cartilage in animal
      models, the main studies on the epidemiology of limbs osteoarthritis and clinical
      trials on rehabilitation. RESULTS: In vitro studies have demonstrated that some
      molecules are involved in the transduction of mechanical stress into
      intracellular biological event. Chondrocytes and cartilage are sensitive to
      mechanical stress and cartilage extracellular matrix synthesis and degradation
      can be modulated by mechanical events. Applications of cyclic loads usually lead
      to an enhanced matrix synthesis while static loads usually decrease matrix
      production. In animal models, intensive physical activity or immobilization lead
      to cartilage alteration mimicking osteoarthritis. In human, intensive and
      prolonged physical activities are probably associated with hip and knee
      osteoarthritis. However, there is evidence that exercise therapy and continuous
      passive motion have beneficial effects on patients with knee or hip
      osteoarthritis. Fundamental and clinical studies are still needed to determine if
      exercise programs could have an effect on chondromodulation. Continuous passive
      motion could help, in the future, to better understand the relationship between
      mechanical stimulation and cartilage homeostasis. CONCLUSION: Rehabilitation
      could be beneficial in the therapeutic management of limbs osteoarthritis. The
      protocols of rehabilitation should however be more evaluated in controlled
      trials.

PMID- 11587669
TI  - [Reevaluation of physiological mechanisms generating the stretch reflex: new
      hypotheses on the physiopathology of spasticity].
AB  - INTRODUCTION: Spasticity has been defined as tendon reflex exaggeration and
      increased muscle reflex contraction in response to its stretch (Lance, 1980). It
      has been generally admitted that stretch reflex exaggeration was due to myotatic
      reflex hyperexcitability (Ia fibre-motoneurone synapses). This interpretation has
      been recently revisited taking into account neurophysiological data obtained in
      cat and recent data obtained in spastic patients. PROBLEMATICS: Myotatic reflex
      has been described in decerebrate cat in 1924 by Liddel and Sherrington. In 1943,
      Lloyd demonstrated that myotatic reflex was due to monosynaptic Ia fibre
      motoneurone alpha synapses. Almost all the following studies of stretch reflexes
      were devoted to monosynaptic reflexes both in animal and humans. In fact, the
      existence of group II fibres coming also from spindles and some restricted
      experiments performed in man have led to discuss the role of group II fibres in
      the static component of the stretch reflexes. RESULTS: Recent studies performed
      in humans have shown that group II fibres play an important role in the
      development of stretch reflexes in leg muscles and that in spastic hemiplegic
      patients group II fibres facilitatory effects was deeply increased. DISCUSSION:
      Results obtained both in humans and animals suggest that group II fibres play
      also a role in a stretch reflex and led to consider that the pathophysiological
      modifications of group II effects could contribute to spasticity. CONCLUSION:
      Modifications of network fed by group II fibres and modifications of muscular
      fibres intrinsic properties are likely to play a role in the developments of
      spasticity in humans.

PMID- 11587670
TI  - [Total inverted shoulder prosthesis and rotator cuff insufficiency: evaluation
      and determination of anatomical parameters predictive of good functional outcome
      in 21 shoulders].
AB  - OBJECTIVE: Evaluation of the functional results of the Delta 3 inverted shoulder
      prosthesis and determination of a radio-anatomical index predictive of best
      functional outcome. PATIENTS AND METHODS: Retrospective analysis of 19 patients
      (21 shoulders). Clinical (pain, satisfaction, amplitudes, Constant index) and
      radiological (acromio-epiphyseal distance) evaluation at a mean follow up of 13.6
      months. RESULTS: Outcomes concerning pain, quality of life and Constant index
      were good and similar to other series. Few complications were observed. An
      increase of the acromio-epiphyseal distance of 33 to 50% compared to the non
      operated side is associated with a good functional result. CONCLUSION: Our
      results confirm those of other series and show that Delta 3 inverted prosthesis
      is an efficient therapeutic alternative in arthropathy with rotator cuff tears.
      Rehabilitation is fairly short and easy. The increase of the acromio-epiphyseal
      distance determines the tension of the deltoid muscle and could predict a
      favorable outcome.

PMID- 11587671
TI  - [Validation of an evaluation test of activities of daily living behaviour for
      patients with chronic low back pain].
AB  - AIM: The purpose of this study was to validate an evaluation test of the gesture
      behaviour for patients with chronic low back pain. METHOD: Forty-four patients
      (19 females and 25 males) (45.7 +/- 10.8 years) with chronic low back pain (delay
      of pain: 9.8 +/- 9.0 years) took part in an educational back school program. They
      performed 3 tests at the beginning (pre-test), at the end (post-test) and three
      months after the back school program (control): a visual analogic scale, the
      Dallas questionnaire and a gesture evaluation test that is composed of three
      tasks for the pre-test and five tasks for the post-test and the control session.
      RESULTS: Our gesture test was reproducible and sensible. The mean gesture result
      increased significantly after the back school program (39.6 +/- 23.2 % in the pre
      test and 73.4 +/- 12.5 % in the post-test, p < 0.05) and was stabilized at this
      high level (69 +/- 18.8 %) for the control session. The patients demonstrated
      abilities to transfer an appropriate gesture behaviour to new tasks. DISCUSSION
      AND CONCLUSION: This study validated a gesture behaviour test for the patient
      with chronic low back pain. The use of this test during a back school program
      demonstrated an immediate and long lasting effect on the appropriate gesture
      behaviour. However the algo-functional status was increased more belatedly and
      more modestly.

PMID- 11587673
TI  - [What happens to the fibromyalgia syndrome?].
AB  - OBJECTIVE: To realize a clarification about fibromyalgia, attempting to consider
      diagnostic criteria, prevalence, pathophysiology and therapeutic approach.
      METHOD: A systematic literature search was conducted to select articles about
      fibromyalgia and connected diseases. The database are Premedline, Medline and
      Medlineplus. RESULTS: Fifty-eight articles about fibromyalgia and twelve articles
      about connected diseases were selected to realize this review of literature.
      DISCUSSION: Fibromyalgia constitutes a syndrome characterized by widespread
      musculo-skeletal pain, present above the waist and below the waist and in the
      axial skeleton. Widespread pain must have been present for at least three months.
      "Spasmophilie", chronic fatigue syndrome and myofascial syndrome represent
      diseases connected with fibromyalgia: differential diagnosis must be established.
      Researches related to fibromyalgia suggest a reduction of muscular performances
      associated with histological and biochemical anomalies. Patients are
      characterized by shorter and nonrestorative sleep. Psychological, neuroendocrine
      and central alterations appear often associated with fibromyalgia. The reduction
      of pressure tolerance and pain thresholds may be linked to the alterations of
      neuroendocrine substances. Literature recommend a multidisciplinary therapeutic
      approach in management of fibromyalgia. CONCLUSION: The pathophysiologic
      mechanisms in fibromyalgia appear multiple and interdependent. With the aim to
      optimizing treatment, investigations are necessary to determine biochemical
      repercussions of various therapeutic approaches.

PMID- 11587674
TI  - [The shoulder-hand syndrome after stroke: clinical factors of severity and value
      of prognostic score of Perrigot].
AB  - PURPOSE: The purposes of this study were to evaluate the prognostical factors of
      reflex sympathetic dystrophy in stroke patients in attempt to improve the
      Perrigot prognostical score. MATERIAL AND METHOD: This prospective study included
      28 stroke patients with reflex sympathetic dystrophy. An initial clinical
      assessment including Perrigot score was made at the time of admission (before the
      end of the first month) and a second evaluation of reflex sympathetic dystrophy
      at the end of the third month. Patients were assessed using Motricity Index,
      Ashworth scale, de Bats grading (for glenohumeral alignment), Labrousse criteria
      (for reflex sympathetic dystrophy severity), and MADRS depression scale. Sensory
      deficit and unilateral neglect were noted. RESULTS: The length of stay in acute
      ward was 16 days. The Perrigot score was correlated with the reflex sympathetic
      dystrophy severity (r = 0.7, p < 0.0001). It predicted the result of therapy. A
      significant correlation was found between reflex sympathetic dystrophy severity
      and motor deficit (r = -0.591, p = 0.0007) and spasticity (p < 0.05). No relation
      was found with stroke side, unilateral neglect, depression or shoulder
      subluxation. It wasn't possible to improve the Perrigot prognostical score.
      CONCLUSION: Perrigot score predict reflex sympathetic dystrophy severity and the
      result of therapy. The shoulder subluxation which is not included in this score
      appears to be not predictive. Shoulder subluxation is simply a marker of a severe
      paresis.

PMID- 11587675
TI  - [Idiopathic toe walker child. Diagnosis and spontaneous evolution].
AB  - AIM OF THE STUDY: To analyse the clinical, the aetiological aspects, the
      evolution without treatment and the age of correction. MATERIAL: This history of
      69 children admitted between 1973 and 1998 was analysed. Forty-one were reviewed
      during the growth; only 6 were treated. RESULTS: The toe walking was most often
      observed at the beginning of the walk between the age of 12 and 18 months. The
      first examination was made between 1 and 4 year old. The ankle dorsiflexion was
      the same, knee extended or flexed for 41 children and different in 23 cases.
      Identical cases were present in the family in 16 of 33 when the history family
      was analysed. The neurological examination was normal in 46 cases. None of the 69
      children had a neurological impairment. In 32 cases, spontaneous correction
      occurred between 3 and 8 years: all these cases presented an ankle dorsiflexion
      over 10 degrees knee extended. The toe walking persisted in two cases at 10 years
      and in two cases at 12 and 13 years: the dorsiflexion was under 10 degrees, knee
      extended at initial examination in these cases. DISCUSSION AND CONCLUSION: It is
      possible to differentiate the toe walkers with more than 10 degrees of ankle
      dorsiflexion knee extended where the correction is possible without treatment and
      the cases with triceps contracture and less than 10 degrees of ankle dorsiflexion
      where the correction without triceps lengthening is questionnable.

PMID- 11587676
TI  - [Dissociation of retrograde memory impairment in a case of herpetic
      encephalitis].
AB  - OBJECTIVE: To report an uncommon case of memory impairment after
      meningoencephalitis. METHOD: Detailed description of the history, the lesions,
      the evolution and review of the bibliography. RESULTS: A 33 year-old man showed a
      loss of verbal anterograde memory and a dissociation of retrograde memory
      impairment after an herpetic meningo-encephalitis with lesions predominant in the
      left temporal lobe. The patient had impairment of verbal anterograde memory.
      Visual memory, procedural one were intact. He had normal performances in frontal
      tests. Neuropsychological assessment revealed major loss of episodic biographical
      memory and public events memory, but sparing of semantic biographical memory and
      professional knowledge. This patient who was amnesic but who had not difficulties
      with visual memory, procedural memory, frontal abilities and didactic memory
      conserved ability to work. CONCLUSION: This case report emphasize the
      multiplicity of the memory systems and the likely links between episodic
      biographical memory, semantic biographical memory, autobiographic episodic
      memory, public event memory and didactic memory.

PMID- 11587677
TI  - [Fractures of ossified Achilles tendon in cerebral palsy. Apropos of a case].
AB  - PURPOSE: To describe a case of ossification of the Achilles tendon fracture in
      cerebral palsy. METHODS: From the detailed case report, review of the literature
      was performed. RESULTS: A 49 years old patient who have presented a bilaterally
      pain syndrome of the ankles. Clinical investigations showed a bilaterally
      ossification of the Achilles tendon, with a fracture on the left side. The
      evolution was marked by the occurrence of an other fracture on the right side.
      Both needed surgery. Just a few cases of such ossification have been reported in
      literature. This ossification are more often asymptomatic. Complications such
      fracture are rare, no more than 20 cases have been reported, and only one case in
      cerebral palsy. The etiologic factors are multiple, including partial or complete
      rupture or surgery, with a probably great importance of tissular hypoxemia. Men
      older than 40 years old are more often concerned. DISCUSSION: In the majority of
      case ossification of the Achilles tendon are painless, and fortuitously
      discovered. In case of ankle pain syndrome, a research of fracture must be done.
      Standard X-rays and RMI are the more instructive exams for diagnosis. The
      treatment of these fractures is more often the surgery. Orthopaedic treatments
      remain rarely used because of the duration of treatment and of a major risk of
      recurrence. CONCLUSION: In adult cerebral palsy a standard X-rays of the two
      Achilles tendon must be realised in case of the occurrence of an ankle pain
      syndrome especially if an antecedent of Achilles tendon lengthening is known.

PMID- 11587678
TI  - What is achieved by mammographic surveillance after breast conservation treatment
      for breast cancer?
AB  - BACKGROUND: After breast conservation surgery for breast cancer, patients are
      followed up by regular clinical examination and mammography, at intervals which
      vary according to local practice. However, the optimum interval remains unclear
      with current guidelines suggesting mammography should be carried out every 1 to 2
      years. This study has investigated this aspect and, in particular, whether
      mammography or clinical examination or both allowed an early detection of
      recurrence of the disease in the conserved breast. METHODS: A total of 695
      patients who had undergone breast conservation surgery were identified from a
      database of prospectively recorded data during the period 1990 to 1995. Clinical
      examination and annual mammography were performed in accordance with local
      protocol. The results of clinical examination, mammography, and local recurrence
      rates were evaluated. RESULTS: A total of 2,181 mammograms were undertaken in the
      695 patients studied. Local recurrence of disease in the conserved breast
      occurred in 21 patients (3%), at a mean follow-up of 3.5 years. The first
      identification of tumor recurrence was by clinical examination in 11 patients
      with local recurrence, and by the surveillance mammography in the other 10
      patients with local recurrence. Overall, mammography detected the local
      recurrence in 13 of 20 (65%) patients who underwent this examination. In the
      other patients, the recurrence was detected on clinical examination only. In
      addition, in 52 patients, mammography was falsely positive, giving a false
      positive rate of 2.3%. Contralateral cancers in the opposite breast were detected
      in 2 patients. CONCLUSIONS: The detection of local disease after breast
      conservation surgery requires both clinical examination and mammography. In the
      context of our follow-up policy, in 52% of patients with local recurrence, this
      was first identified by clinical examination. Disease recurrence was identified
      in the other 48% of patients by mammographic surveillance. Overall, mammography
      will identify or confirm local recurrence in two thirds of women. However, in a
      small number of cases (2.3% in our series) mammography will give false positive
      results. New imaging modalities to assist in the diagnosis of local recurrence of
      disease after breast conservation surgery are required.

PMID- 11587679
TI  - Comparison of open and laparoscopic treatment of acute appendicitis.
AB  - BACKGROUND: Appendectomy can be performed using either a laparoscopic or an open
      technique. This study compares the outcome of patients treated for acute
      appendicitis by open appendectomy with the outcome of those undergoing
      laparoscopic appendectomy. METHODS: Patients undergoing appendectomy at The Mount
      Sinai Hospital between 1994 and 1998 were studied. Outcome of patients having
      open appendectomy was compared with that of patients having laparoscopic
      appendectomy. RESULTS: Seven hundred fifty-eight patients underwent appendectomy
      for acute appendicitis during the 5-year study period. Two hundred seventy-one
      (36%) had open appendectomy and 487 (64%) had laparoscopic appendectomy. Patients
      subsequently found to have a normal appendix had the highest rate of laparoscopic
      appendectomy, whereas those with gangrenous appendicitis were most likely to have
      open appendectomy (P <0.05). There was a significant decline in the postoperative
      length of stay for open cases during the length of the study. In the final year,
      the difference in length of stay between open and laparoscopic appendectomy was
      only 1 day. Patients with gangrenous appendicitis had a significantly longer
      length of stay than did patients with a normal appendix or suppurative
      appendicitis. The hospital cost of laparoscopic appendectomy was greater than
      that for open appendectomy but the extra expenditure in the operating room was
      offset by the longer length of stay of the patients having open surgery.
      CONCLUSIONS: Differences in outcome between open and laparoscopic appendectomy
      are minor. In this study, more difficult cases with gangrenous appendicitis were
      more likely to require open appendectomy whereas milder forms of appendicitis,
      especially in women, were more likely to be treated by laparoscopy. Savings from
      the slightly shorter hospital stay after laparoscopic appendectomy are offset by
      the higher surgical cost of the laparoscopic equipment.

PMID- 11587680
TI  - Prospective randomized trial comparing Nissen to Nissen-Rossetti technique for
      laparoscopic fundoplication.
AB  - BACKGROUND: It has been suggested that division of the short gastric vessels
      (SGV) provides a more floppy Nissen fundoplication, for the treatment of reflux
      disease. The aim of the study was to assess whether Nissen fundoplication with
      division of SGV is associated with improved clinical outcome and laboratory
      findings. METHODS: Fifty-six consecutive patients with gastroesophageal reflux
      disease (GERD) were randomly assigned to have a laparoscopic Nissen
      fundoplication either with division (24 patients; 15 men; mean age 51 +/- 15
      years) or without division (32 patients; 23 men, mean age 47 +/- 14 years) of the
      SGV. Preoperative and postoperative investigation included clinical assessment,
      esophagoscopy, esophagogram, esophageal manometry, and 24-hour ambulatory
      esophageal pH monitoring. RESULTS: Division of the SGV resulted in a significant
      increase of the operating time (P <0.0001). The operation abolished reflux in
      both groups. Also, both types of Nissen fundoplication significantly increased
      the amplitude of peristalsis at distal esophagus (division group: from 56 +/- 20
      mm Hg to 64 +/- 25 mm Hg, P = 0.01; nondivision group: from 65 +/- 27 mm Hg to 75
      +/- 26 mm Hg, P <0.001) and the lower esophageal sphincter pressure (division
      group: from 16 +/- 10 mm Hg to 24 +/- 7 mm Hg, P <0.001; nondivision group: from
      22 +/- 8 mm Hg to 28 +/- 5 mm Hg, P <0.001). No differences in the incidence of
      postoperative severe dysphagia (division group: 5 of 24; nondivision group: 3 of
      32) and overall esophageal transit were accounted between groups. However,
      division of the SGV was associated with a significant increased incidence of gas
      bloating syndrome (division group, 13 of 24, versus nondivision group, 9 of 32, P
      = 0.02). CONCLUSIONS: Division of the SGV at laparoscopic Nissen fundoplication
      for GERD does not improve clinical outcome and laboratory findings, while it is
      associated with prolongation of the operating time and increased incidence of gas
      bloating syndrome.

PMID- 11587681
TI  - Electrophysical properties of electrosurgery and capacitive induced current.
AB  - BACKGROUND: Although electrosurgery is one of the most commonly used technologies
      in the operating room, its electrophysical properties, including the potential
      for complications, are poorly understood by many surgeons. METHODS: We describe
      the experimental simulation of a highly unusual complication that occurred during
      a surgical procedure requiring concurrent use of monopolar and bipolar
      electrosurgery. RESULTS: Capacitive induced current from an activated monopolar
      electrode to the bipolar cord was reproduced and consistently led to full
      thickness burns in our experiments. CONCLUSIONS: Surgeons should be familiar with
      the principles of electrosurgery, its electrophysical properties, and possible
      complications.

PMID- 11587682
TI  - Urinary retention after elective cholecystectomy.
AB  - BACKGROUND: There are few reports about urinary retention rate after elective
      cholecystectomy. We designed a prospective study to assess the problem. METHODS:
      A total of 121 female and 19 male patients were included in the study with a
      prospective study protocol. Laparoscopic cholecystectomy was performed in 107
      patients and open cholecystectomy in 33 patients. RESULTS: Neither gender nor age
      affected rate. Postoperative micturition difficulty developed in 10 patients. Of
      these patients, 9 could void with helping measures, and only 1 needed
      catheterization. Only 1 patient who underwent laparoscopic surgery required
      catheterization (0.7%). The open approach caused a higher incidence of
      postoperative micturition difficulty than did the laparoscopic approach (15.2%
      versus 4.7%; P = 0.04). Only large amounts of perioperative fluid administration
      and meperidine use had statistically significant effects on micturition problems.
      CONCLUSIONS: Urinary retention is a rare complication after elective
      cholecystectomy. Helping measures are very effective and should be tried before
      inserting a urethral catheter.

PMID- 11587683
TI  - Quality of life after pylorus-preserving pancreatoduodenectomy.
AB  - BACKGROUND: With increasing numbers of long-term survivors after pylorus
      preserving pancreatoduodenectomy (PPPD), postoperative quality of life (QOL) has
      become a great concern. However, few reports are available on data of the
      postoperative changes in QOL after PPPD. METHODS: A total of 20 patients were
      studied regarding QOL before and at short term (within 2 months), intermediate
      term (6 months), and long term (1 year) after PPPD, using a questionnaire. The
      questionnaire consisted of 13 physical and 10 psychosocial items. The medical
      records were also reviewed to evaluate objective nutritional status. Factors
      predicting delayed recovery of QOL were examined at intermediate term by
      univariate and multivariate analyses. RESULTS: Overall and physical QOL scores
      returned to the preoperative level at intermediate term after PPPD, showing
      parallel changes with the objective nutritional status. However, the scores of
      psychosocial condition, which reflected the patient's mental health, remained low
      even at long term. QOL scores at intermediate term in patients with pancreatic
      carcinoma were significantly lower than those with other diseases. Univariate
      analysis showed that preoperative body weight loss, impaired preoperative
      pancreatic exocrine function, long operative time, intraoperative radiotherapy,
      pancreatic carcinoma, and postoperative diarrhea were factors predicting the
      delayed recovery of QOL. Multivariate analysis revealed that preoperative
      pancreatic exocrine function significantly affected the delayed recovery of QOL.
      CONCLUSIONS: Preoperative supplement of pancreatic enzymes together with
      perioperative mental care would improve QOL at long term after PPPD.

PMID- 11587684
TI  - Operative and long term results after surgery for chronic radiation enteritis.
AB  - BACKGROUND: About one third of patients with chronic radiation enteritis will
      need to be operated on during follow-up. Morbidity and life expectancy after
      resection and conservative surgical management for chronic radiation enteritis
      have not been well documented. METHODS: From 1984 to 1994, 109 patients were
      operated on with a mean follow-up of 40 months (range 1 to 293). Postoperative
      mortality, early and late morbidity, long-term survival were studied in patients
      after resection (n = 65) and after conservative surgical management (n = 42), and
      in patients after planned or emergency procedure. Existence of possible risk
      factors for reoperation after a first surgical procedure was analyzed. RESULTS:
      Five (5%) patients died in the postoperative course. Operative mortality was
      significantly higher when the procedure was performed as an emergency (P <0.05).
      Although not statistically significant, mortality was higher in the resection
      group (5% versus 0%). Thirty-three (30%) patients experienced postoperative
      complications including anastomotic leak in 11. Morbidity was not statistically
      related to the nature of the treatment (ie, conservative versus resection) or to
      the indication (emergency versus elective). During follow-up, reoperation was
      required in 40% of the patients, because of recurrence of digestive symptoms
      suggestive of chronic radiation enteritis; the reoperation rate was higher in the
      patients of the conservative group (50% versus 34%). Overall survival, after a
      mean follow-up of 40 months in patients without cancer recurrence was 85% at 1
      year and 69% at 5 years after surgery, respectively. Overall survival was
      influenced by the nature of the treatment with 51% and 71% 5-year survival after
      conservative and resection treatment, respectively. CONCLUSIONS: Despite high
      initial mortality and morbidity rates, life expectancy in patients with chronic
      radiation enteritis without recurrence of their previous neoplastic disease was
      good. Resection seems to provide a smaller reoperation rate and a better 5-year
      survival, but a higher postoperative mortality.

PMID- 11587685
TI  - Is a preoperative multidiagnostic approach to predict surgical resectability of
      periampullary tumors still effective?
AB  - BACKGROUND: Multimodality staging is recommended in patients with periampullary
      tumors to optimize preoperative determination of resectability. We investigated
      the potency of currently used diagnostic procedures in order to determine
      resectability. METHODS: Ninety-five consecutive patients with periampullary
      tumors prehospitally staged resectable underwent preoperative diagnostic tests:
      helical-computed tomography (CT) with maximum intensity projection of arterial
      vessels (MIP), magnetic resonance imaging (MRI), magnetic resonance
      cholangiopancreaticography (MRCP), endoscopic ultrasonography (EUS), endoscopic
      retrograde cholangiopancreaticography (ERCP), digital subtraction angiography
      (DSA), and positron emission tomography (PET). Diagnoses were verified by surgery
      and histopathology. RESULTS: In 45 patients with benign and 50 patients with
      malignant periampullary tumors sensitivity for tumor diagnosis was 89% to 96% in
      CT, MRI, EUS, and PET. Small tumors were best diagnosed by EUS (100%). Diagnosis
      of malignancy was made with 85% (EUS), 83% (CT), 82% (PET), and 72% (MRI)
      accuracy. Arterial vessel infiltration was best predicted by CT/MIP with an
      accuracy of 85%. For venous vessel infiltration MRI reached 85% accuracy.
      Accuracy rates for local nonresectability were 93% (EUS), 92% (MRI), and 90%
      (CT). Two and 4 of 8 patients with distant metastases were identified by CT and
      PET, respectively. The correct diagnosis of malignancy and determination of
      resectability was made by CT in 71% and by MRI in 70%. Biliary stenting reduced
      accuracy of CT diagnosis of malignancy from 88% to 73%. CONCLUSIONS: CT obtained
      before stenting was the single most useful test, providing correct diagnosis in
      88% and resectability in 71% of patients. If no tumor is depicted in CT, EUS
      should be added. Uncertain venous vessel infiltration can be verified by MRI or
      EUS. Angiography should no longer be a routine diagnostic procedure. Equivocal
      tumors or possible metastasis may be further examined with PET.

PMID- 11587686
TI  - The tail of the learning curve for laparoscopic cholecystectomy.
AB  - BACKGROUND: This study estimates the number of laparoscopic cholecystectomies
      required until improvement ceases, assesses the magnitude of such improvement,
      and provides some insight into the mechanism by which it takes place. METHODS:
      Data from 500 consecutive laparoscopic cholecystectomies were analyzed from a
      prospective data base for number of short and long operations and operative time.
      RESULTS: There was a 40% decrease (P <0.05) in average operative time over the
      first 200 operations. Significant decrease in the number of longer operations,
      increase of shorter cases, and decrease in the range of operative time were
      noted. The major contributor was a marked shortening of longer cases, without
      much increased speed of shorter operations. CONCLUSIONS: For laparoscopic
      cholecystectomy, improvement persists for about 200 operations, resulting in a
      40% reduction in operative time. The primary mechanism of improvement seems to be
      an ability to deal more effectively with difficult cases.

PMID- 11587687
TI  - Exporting a technical skills evaluation technology to other sites.
AB  - BACKGROUND: The Objective Structured Assessment of Technical Skill (OSATS) is a
      multistation performance-based examination that assesses the technical skills of
      surgery residents. This study explores the implementation issues involved in
      remote administration of the OSATS focusing on feasibility and the psychometric
      properties of the examination. METHODS: An eight-station OSATS was administered
      to surgical residents in Los Angeles and Chicago. The University of Toronto and
      the local institutions shared responsibility for organization and administration
      of the examination. RESULTS: There was good reliability for both the checklist
      (alpha = 0.68 for LA, 0.73 for Chicago) and global rating forms (alpha = 0.82 for
      both sites). Both iterations also showed evidence of construct validity, with a
      significant effect of training year for the checklist and global rating forms at
      both sites (analysis of variance: F = 8.66 to 19.93, P <0.01). Despite some
      challenges, the model of central organization and peripheral delivery was
      effective for the administration of the examinations. CONCLUSIONS: Two iterations
      of the OSATS at remote sites demonstrated psychometric properties that are highly
      consistent with previously reported data suggesting that the examination is
      portable. Both faculty and residents indicated satisfaction with the examination
      experience. A model of central administration with peripheral delivery was
      feasible and effective.

PMID- 11587688
TI  - Pancreatic transection using ultrasonic dissector in pancreatoduodenectomy.
AB  - BACKGROUND: Pancreatoenterostomic leakage after pancreatoduodenectomy may be
      caused partly by pancreatic juice leakage from transected branch pancreatic ducts
      on the pancreatic cut surface that do not drain into the main pancreatic duct
      after pancreatectomy. METHODS: We devised a new technique of pancreatic
      transection using an ultrasonic dissector followed by duct-to-mucosa
      pancreatojejunostomy, in order to prevent pancreatoenterostomic leakage after
      pancreatoduodenectomy in patients with a soft pancreas and a small main
      pancreatic duct. During pancreatic transection, branch pancreatic ducts and blood
      vessels are adequately skeletonized and securely ligated. The pancreatic duct is
      anastomosed to the full thickness of the jejunum with four to six interrupted
      sutures. RESULTS: Ten patients with a nondilated pancreatic duct (2 to 3 mm)
      underwent pancreatoduodenectomy by the present method. During pancreatic
      transection, 24 to 35 ducts including the pancreatic ducts and blood vessels were
      skeletonized and ligated. Postoperatively, no patients developed
      pancreatojejunostomic leakage. The present method may prevent
      pancreatoenterostomic leakage after pancreatoduodenectomy.

PMID- 11587689
TI  - Easier hepatic resections with a straight needle.
AB  - BACKGROUND: A stainless-sheathed, straight needle with a hook near the top of the
      inner needle was designed to facilitate hepatic resections. METHODS: First, using
      this needle, two rows of interlocking mattress sutures were made along the
      division line; then, hepatic transection was performed between these rows by
      electrocautery or forceps. RESULTS: Since 1997, we have performed this kind of
      hepatic resections in 43 cases, including 9 right lobectomies, 5
      bisegmentectomies, 7 segmentectomies, 4 subsegmentectomies, 2 partial
      hepatectomies, 15 left lateral segmentectomies, and 1 hepatorrhaphy. In most
      cases, intraoperative hemorrhage was minimal. Neither specified inflow nor
      backflow control procedures were needed. CONCLUSION: Use of this needle may
      reduce the difficulty of the technique and blood loss for right hepatic
      lobectomy, left lateral segmentectomy, and some segmental or partial hepatectomy
      procedures.

PMID- 11587690
TI  - A simple technique for vascular control during hepatectomy: the half-Pringle.
AB  - BACKGROUND: Hemorrhage during hepatectomy remains the major cause of morbidity
      and mortality associated with this surgery. Traditionally, a Pringle technique is
      employed to reduce vascular inflow during parenchymal transection. METHODS: This
      paper describes a simple method to achieve unilateral vascular control during
      hepatic surgery. The technique has been used in the most recent 10 hepatectomies
      performed in this unit. RESULTS: During the hepatectomies, the pattern of
      vascular inflow was documented with a series of color Doppler images. These
      images illustrated the effectiveness of the maneuver.

PMID- 11587691
TI  - Reanimation of the paralyzed face by indirect hypoglossal-facial nerve
      anastomosis.
AB  - BACKGROUND: The results of indirect hypoglossal facial nerve anastomosis with
      interposition of a free nerve graft, end-to-end to the periferal facial nerve
      stump, and end-to-side to the hypoglossal nerve are prospectively evaluated. This
      technique is supposed to overcome loss of hypoglossal function. METHODS: Tongue
      function in 39 consecutive patients and facial reanimation in 29 patients who
      completed 24 months follow-up were assessed. Facial nerve function was judged
      using the House-Brackmann (HB) grading system. RESULTS: Tongue movements were
      normal in all operated on patients. Initial facial movements occurred on average
      7.5 months postoperatively. The results were graded HB II in 6 (20.9%), HB III in
      13 (44.6%), HB IV in 7 (24.1%), HB V in 2 (6.8%) patients, and HB VI in 1 (3.4%)
      patient. The results were significantly better in young patients and when a short
      time interval between paralysis and surgery existed. CONCLUSIONS: Indirect
      hypoglossal-facial anastomosis is the preferred technique in most patients for
      whom the classical direct hypoglossofacial anastomosis is indicated.

PMID- 11587692
TI  - Is there a role for curative surgery for pelvic recurrence from rectal carcinoma
      in the presence of hydronephrosis?
AB  - BACKGROUND: The prognosis for patients with recurrent rectal adenocarcinoma is
      not uniformly fatal if one can safely and selectively reoperate on a subset of
      patients with resectable disease. Even with careful selection, many patients
      undergo exploratory laparotomy and do not have resectable disease. We have
      reported that the presence of hydronephrosis in the setting of recurrent rectal
      carcinoma portends a poor outcome because of invariable association with
      unresectable disease. The purpose of this study was to update our experience of
      patients presenting with unilateral or bilateral hydronephrosis and recurrent
      rectal cancer. METHODS: A retrospective chart review of 142 patients with
      recurrent rectal cancer evaluated at our institution from January 1989 to
      December 1999 was performed. RESULTS: Twenty-seven of 142 patients referred for
      the management of recurrent rectal cancer had unilateral or bilateral
      hydronephrosis. Fifteen (55%) of these patients had distant metastatic disease.
      Twelve patients (45%) with hydronephrosis and local recurrent disease on
      evaluation were analyzed. Six of the 12 patients underwent exploratory
      laparotomy, with none found to have resectable disease. Their mean survival after
      diagnosis of recurrent disease was 14 months. CONCLUSIONS: Based on our results,
      the presence of hydronephrosis (unilateral or bilateral) in recurrent rectal
      adenocarcinoma portends a survival equivalent to the presence of distant
      metastasis. Therefore, we do not believe potential curative surgery has a role
      for patients with locally recurrent rectal adenocarcinoma in the presence of
      hydronephrosis.

PMID- 11587693
TI  - Correlating functional staging to effective treatment of acute surgical illness.
AB  - BACKGROUND: Proinflammatory and anti-inflammatory events may eventually trigger
      host response, which acting via a broad spectrum of complex biological processes
      and molecular interactions may either enhance or resolve the symptoms of acute
      surgical illness (ASI). Staging the sequence of biological events that take place
      at the cellular level during the development of ASI may provide leads to
      effective stage-specific treatments. In line with the hypothesis that proper
      timing of therapeutic intervention may be crucial to the management of the
      disease, we have attempted in this review to correlate functional staging to
      effective treatment of ASI. DATA SOURCE: The present report proposes a conceptual
      synthesis on the biogenesis and treatment of ASI that is based on known molecular
      and cellular aspects of human inflammatory sequence and patient data from
      clinical trials. It also introduces proper timing of therapeutic intervention as
      a potentially important determinant for the successful outcome of the disease
      process. CONCLUSIONS: Progress in understanding the biogenesis of ASI did not
      result in successful therapeutic developments as yet. The challenge ahead should
      be a better understanding of the dynamics of the various processes and regulators
      in appropriate animal and clinical models of ASI, in order to properly intervene
      and direct effective therapies for the benefit of critically ill patients.

PMID- 11587694
TI  - Pneumatosis cystoides intestinalis complicating carcinoma of the small intestine.

PMID- 11587695
TI  - Jugular phlebectasia manifesting as an unusual neck mass in a child.

PMID- 11587696
TI  - Predictive factors for the type of surgery in acute cholecystitis.
AB  - BACKGROUND: Whereas early cholecystectomy is accepted as the optimal timing for
      surgery, the best treatment modality for acute cholecystitis (AC) is still under
      debate. In this series, we aimed to assess the current treatment of AC in a
      single institution. In addition, preoperative criteria were defined predicting
      the severity of inflammation. METHODS: From January 1995 to June 1999, 236
      patients undergoing cholecystectomy for AC were prospectively evaluated. Outcome
      measures were the treatment modality, the severity of inflammation, white blood
      cell (WBC) count, C-reactive protein (CRP), morbidity, and hospital stay.
      RESULTS: There were 115 laparoscopic cholecystectomies (LC), 77 primary open
      cholecystectomies (OC), and 44 conversions (CON) to OC. Patients with LC were
      significantly younger, in better condition, with a shorter duration of symptoms
      and lower CRP levels and WBC counts compared with OC and CON (P <0.001).
      Postoperative complications, reinterventions, and mean hospital stay were
      significantly increased after OC and CON (P <0.001). Overall mortality was 2.5%.
      Advanced AC was predominantly found in OC and CON (P <0.001). Patients with
      advanced AC were significantly older, predominantly male, and had a prolonged
      duration of symptoms as well as increased CRP levels and WBC counts (P <0.001).
      The conversion rate increased from 10% for mild AC up to 48% for necrotizing AC.
      CONCLUSIONS: Based on laboratory (CRP, WBC), demographic (age, sex), and
      individual (American Society of Anesthesiologists classification, duration of
      symptoms) findings, it is possible to reliably predict the severity of
      inflammation. Therefore, an individualized surgical approach can be used for each
      patient and type of AC.

PMID- 11587697
TI  - Correlation of serum basic fibroblast growth factor levels with clinicopathologic
      features and postoperative recurrence in hepatocellular carcinoma.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF) is an important positive
      regulator of tumor angiogenesis. This study evaluated the role of serum bFGF as a
      biological marker of tumor invasiveness and postresection recurrence in
      hepatocellular carcinoma (HCC). METHODS: Concentrations of bFGF in preoperative
      serum samples in 88 patients undergoing resection of HCC were measured by a
      quantitative enzyme-linked immunosorbent assay. A single pathologist performed
      histopathologic examination of all tumor specimens. All patients were
      prospectively monitored for tumor recurrence. RESULTS: The preoperative serum
      bFGF levels ranged from <0.22 to 71.2 pg/mL (median 10.8 pg/mL). There was
      significant correlation between high serum bFGF levels and large tumor >5 cm,
      presence of venous invasion or advanced pTNM stage. Patients with a serum bFGF
      level >10.8 pg/mL had worse disease-free survival than those with a level <10.8
      pg/mL (median disease-free survival 11.2 versus 20 months, P = 0.044). Serum bFGF
      level >10.8 pg/mL (P = 0.035) and tumor size >5 cm (P = 0.004) were independent
      preoperative factors that predicted early recurrence after resection of HCC.
      CONCLUSIONS: This study supports a role of bFGF in tumor growth and invasion in
      HCC. A high preoperative serum bFGF level appears to be predictive of invasive
      tumor and early postoperative recurrence. The clinical implications of serum bFGF
      level in HCC warrant further investigation.

PMID- 11587698
TI  - Urban injuries in Tehran: demography of trauma patients and evaluation of trauma
      care.
AB  - Trauma now attracts more attention than ever before as a major cause of death and
      disability in developed and developing countries. To describe the characteristics
      and outcome of injuries in our environment, and to identify and discuss possible
      preventative and management protocols that may also be adopted in developing
      countries, we designed a prospective study on all trauma patients consecutively
      attending three emergency departments over a period of 1 year in Tehran, Iran.
      Among the total of 58013 patients studied, workers were the most vulnerable
      occupational group and deserve special preventative measures. The high frequency
      of traffic (especially pedestrian) accidents suggests that considerable progress
      is required in preventing these injuries. Our hospitalized patients were
      comparable with patients in the Major Trauma Outcome Study (m=0.890), and the z (
      15.485) and w (-2.447) statistics showed an unsatisfactory quality of care, which
      may partly be due to less usage of ambulances, the long time of transportation to
      hospital, frequent referrals between centres, and delayed and inadequate
      resuscitation by the emergency services. Based on our findings and the fact that
      the positive effect of trauma systems on outcome has been well documented, we
      suggest that an integrated trauma system be established in Tehran to improve the
      quality of trauma care.

PMID- 11587699
TI  - The paper-clip modification to the vessel loop 'shoelace' technique for delayed
      primary closure of fasciotomies.

PMID- 11587700
TI  - Plate osteosynthesis for pseudarthrosis of the humeral shaft.

PMID- 11587701
TI  - Internal fixation of scaphoid non-union: a comparative study of three methods.
AB  - In this study we compared the results of three methods of fixation for scaphoid
      non-union. The implants used were the AO 2 mm mini-fragment screw, the Herbert
      screw and the Kirschner (K) wires. Between 1990 and 1999, 132 patients underwent
      surgery for scaphoid fractures. We used the modified Filan and Herbert
      classification. Patients with acute fractures and patients requiring vascularised
      bone grafts were excluded. Twenty-six non-unions were fixed with an AO mini
      fragment screw, 58 with a Herbert screw, and nine with K-wires. Radiological
      union was achieved in 85% of cases using the AO screw, 77% using the Herbert
      screw and 55% using the K-wire fixation. Statistically there was no significant
      difference between the AO and Herbert screw groups in terms of rate and speed of
      radiological union. The mechanical strength of the implant and the compression
      achieved did not seem to influence the union rate and speed. The type of bone
      graft (iliac crest or distal radius) did not significantly affect the union
      rates. Finally, K-wire fixation, either as a primary method or as a salvage
      procedure, produced inferior results and required prolonged immobilisation in
      plaster.

PMID- 11587702
TI  - Should Os calcis fractures in smokers be fixed? A review of 40 patients.

PMID- 11587703
TI  - Review of the radiology in randomised controlled trials in open reduction and
      internal fixation (ORIF) of displaced intraarticular calcaneal fractures.
AB  - The aim of this study was to assess the radiological evaluation of all
      prospective, randomised, controlled trails of displaced intraarticular calcaneal
      fractures. A systematic review of the literature, of which only three of 296
      references were randomised and controlled, were examined in a blinded fashion.
      All had preoperative coronal CT for Sander's classification and used a lateral
      surgical approach or conservative treatment. Thordason (15 patients/11 controls)
      used interoperative lateral and axial X-rays. Bohler's angle increased on average
      from 11 to 26 degrees (P<0.001) postoperatively, but decreased (9-8 degrees ) in
      the conservative group. The posterior facet residual displacement was 1.1 and 4.7
      mm, respectively. O'Farrell (12 patients/12 controls) showed 8 out of 12 had
      Bohler's and Gissane's angle partially or fully restored postoperatively, and not
      conservatively. Parmar (25 patients/31 controls) used preoperative lateral
      radiographs, but failed with CT to grade the postoperative reduction, whilst the
      conservative group was unaltered. There was no systematic, blinded assessment of
      the change in radiology by the operative intervention. Overall there was weak
      evidence to support ORIF. In conclusion, there are only three randomised,
      controlled studies involving small numbers of patients, which showed improved
      plain radiographic anatomical alignment, in the postoperative but not
      conservative group. Further prospective randomised, controlled trials with
      independent and blinded assessment with accurate CT and clinical evaluation will
      be required before ORIF can be adopted as the best practice.

PMID- 11587704
TI  - Operative stabilisation of painful non-united multiple rib fractures.

PMID- 11587705
TI  - Complete small bowel transection following lap-belt injury.

PMID- 11587706
TI  - Abstracts from the 2000 British Trauma Society meeting.

PMID- 11587707
TI  - Synergistic mu-opioid and 5-HT1A presynaptic inhibition of GABA release in rat
      periaqueductal gray neurons.
AB  - The periaqueductal gray (PAG) plays a critical role in descending
      antinociception. In mechanically dissociated rat PAG neurons, pharmacologically
      separated spontaneous GABAergic miniature inhibitory postsynaptic currents
      (mIPSCs) were recorded using the nystatin-perforated patch technique. Both DAMGO,
      a specific mu-opioid receptor agonist, and serotonin inhibited mIPSC frequency in
      a dose-dependent manner without affecting mIPSC amplitude, respectively, in the
      same PAG neurons. The presynaptic opioid effect was blocked by a specific mu
      opioid receptor antagonist, CTOP. The presynaptic serotonergic effect was
      mimicked by a specific 5-HT(1A) receptor agonist, 8-OH-DPAT, and blocked by the
      specific antagonist, NAN-190. These opioidergic and serotonergic inhibitions of
      GABA release employed the similar intracellular mechanism of opening 4-AP
      sensitive K(+) channels via GTP-binding proteins (G-proteins). Subthreshold
      concentrations of DAMGO (3 nM) significantly decreased mIPSC frequency with
      subthreshold concentrations of serotonin (3 nM) and this effect was completely
      blocked by pretreatment with N-ethylmaleimide (NEM), a PTX-sensitive G-protein
      inhibitor. In contrast, maximum doses of DAMGO (10 microM) did not further
      inhibit mIPSC frequency with maximum doses of serotonin (10 microM). In
      conclusion, activation of presynaptic mu-opioid and 5-HT(1A) receptors
      synergistically inhibited GABA release. These results suggest a cellular
      mechanism within PAG for the analgesic effectiveness of combined therapies using
      opioids in conjunction with classes of anti-depressants which increase synaptic
      serotonin levels.

PMID- 11587708
TI  - Evidence for distinct conformations of the two alpha 1 subunits in diazepam-bound
      GABA(A) receptors.
AB  - Benzodiazepines allosterically modulate GABA(A) receptors to increase currents
      induced by submaximal GABA concentrations. Benzodiazepine-induced conformational
      changes in the transmembrane domain increase the reactivity of cysteines
      substituted for a subset of residues in the alpha(1) subunit M3 membrane-spanning
      segment. With the cysteine-substitution mutant alpha(1)F296Cbeta(1)gamma(2) we
      previously noted that p-chloromercuribenzenesulfonate (pCMBS(-)) modification in
      the presence of diazepam potentiated subsequent GABA-induced currents. In
      contrast, pCMBS(-) modification in the presence of GABA caused inhibition of
      subsequent responses. We now show that in the presence of diazepam, pCMBS(-) only
      reacts with the engineered cysteine in one of the two alpha subunits; whereas, in
      the presence of GABA, pCMBS(-) reacts with the cysteine in the other alpha
      subunit, or with both cysteines. This implies that the two alpha subunits have
      distinct conformations in the diazepam-bound state. Based on analysis of single
      channel kinetic data, others have hypothesized that diazepam only alters the GABA
      affinity of one of the two GABA binding sites. The results presented here provide
      structural evidence to support the hypothesis that diazepam binding only alters
      the conformation of one of the two alpha subunits in a GABA(A) receptor and
      provides new insights into the mechanism of allosteric potentiation by
      benzodiazepines.

PMID- 11587709
TI  - Seizures induced by intracerebral administration of pyridoxal-5'-phosphate:
      effect of GABAergic drugs and glutamate receptor antagonists.
AB  - Pyridoxal-5'-phosphate (PLP), the cofactor of glutamate decarboxylase,
      paradoxically induces convulsions when injected intracranially in adult mammals.
      We have tested the effect of some GABAergic and antiglutamatergic drugs on the
      behavioral and electroencephalographic (EEG) seizures produced by
      intracerebroventricular (i.c.v.) microinjection of 1 micromol PLP in the rat. PLP
      induced barrel turning, running fits and tonic-clonic convulsions, which started
      5-10 min after recovery from the anesthesia (halothane), peaked at 20 min and
      disappeared at about 50 min. These symptoms were accompanied by frequent high
      amplitude EEG spike burst discharges. Pyridoxal, pyridoxamine-5'-phosphate or
      deoxypyridoxine were ineffective. The i.c.v. microinjection of the GABAergic
      compounds muscimol, isoguvacine, aminooxyacetic acid or GABA itself,
      significantly protected against PLP effects. In contrast, the NMDA receptor
      antagonists MK-801 and the non-NMDA receptor antagonist NBQX, failed to protect
      and induced motor alterations and mortality. We conclude that a temporary
      decrease of the GABA(A) receptor function is involved in the convulsant effect of
      PLP. This decrease might be due to the formation of a Schiff base between the
      carbonyl group of PLP and the epsilon-amino group of a functionally crucial
      lysine residue located in one extracellular loop of the GABA(A) receptor.

PMID- 11587710
TI  - GABA(B) receptors modulate short-term potentiation of spontaneous excitatory
      postsynaptic currents in the rat supraoptic nucleus in vitro.
AB  - High-frequency stimulation of afferents to the supraoptic nucleus (SON) results
      in a robust increase in the frequency and amplitude of pharmacologically
      isolated, tetrodotoxin-resistant, miniature excitatory postsynaptic currents
      (mEPSCs) lasting for 5-20 min. This increase in mEPSC frequency, termed short
      term potentiation (STP), is tightly coupled to increases in action potential
      firing in magnocellular neurons (MCNs) suggesting a functional role for STP.
      gamma-Aminobutyric acid (GABA), acting selectively on GABA(B) receptors, has been
      shown to modulate action potential-dependent EPSCs, as well as mEPSCs in this
      nucleus. In this study, we examined the role of GABA in STP. Using in vitro
      hypothalamic slices containing the SON and the nystatin perforated-patch
      recording technique to record from MCNs, we tested the hypothesis that GABA
      modulates STP. Baclofen, a GABA(B) receptor agonist, caused a reversible decrease
      in the frequency of mEPSCs as well as a reduction in the magnitude and duration
      of STP. GABA(B) receptor antagonists blocked the baclofen-induced decrease in
      mEPSC frequency and reduction in STP. In addition, the antagonists by themselves
      increased basal mEPSC frequency while prolonging the duration of STP in most
      cells. By contrast, picrotoxin, a GABA(A) chloride channel blocker, had no effect
      on STP.These findings indicate that GABA is tonically present in the SON and its
      action at the GABA(B) receptor may determine the magnitude and duration of STP.

PMID- 11587711
TI  - Opioid receptor regulation of muscarinic acetylcholine receptor-mediated synaptic
      responses in the hippocampus.
AB  - A common feature of many synapses is their regulation by neurotransmitters other
      than those released from the presynaptic terminal. This aspect of synaptic
      transmission is often mediated by activation of G protein coupled receptors
      (GPCRs) and has been most extensively studied at amino acid-mediated synapses
      where ligand gated receptors mediate the postsynaptic signal. Here we have
      investigated how opioid receptors modulate synaptic transmission mediated by
      muscarinic acetylcholine receptors (mAChRs) in hippocampal CA1 pyramidal
      neurones. Using a cocktail of glutamate and gamma-amino-butyric acid (GABA)
      receptor antagonists a slow pirenzepine-sensitive excitatory postsynaptic
      potential (EPSP(M)) that was associated with a small increase in cell input
      resistance could be evoked in isolation. This response was enhanced by the
      acetylcholine (ACh) esterase inhibitor physostigmine (1 microM) and depressed by
      the vesicular ACh transport inhibitor vesamicol (50 microM). The mu-opioid
      receptor agonists DAMGO (1-5 microM) and etonitazene (100 nM), but not the delta-
      and kappa-opioid receptor selective agonists DTLET (1 microM) and U-50488 (1
      microM), potentiated this EPSP(M) (up to 327%) without affecting cell membrane
      potential or input resistance; an effect that was totally reversed by naloxone (5
      microM). In contrast, postsynaptic depolarizations and increases in cell input
      resistance evoked by carbachol (3 microM) were unaffected by DAMGO (1-5 microM)
      but were abolished by atropine (1 microM). Taken together these data provide good
      evidence for a mu-opioid receptor-mediated presynaptic enhancement of mAChR
      mediated EPSPs in hippocampal CA1 pyramidal neurones.

PMID- 11587712
TI  - Peripheral withdrawal recruits distinct central nuclei in morphine-dependent
      rats.
AB  - This study examined if brain pathways in morphine-dependent rats are activated by
      opioid withdrawal precipitated outside the central nervous system. Withdrawal
      precipitated with a peripherally acting quaternary opioid antagonist (naloxone
      methiodide) increased Fos expression but caused a more restricted pattern of
      neuronal activation than systemic withdrawal (precipitated with naloxone which
      enters the brain). There was no effect on locus coeruleus and significantly
      smaller increases in Fos neurons were produced in most other areas. However in
      the ventrolateral medulla (A1/C1 catecholamine neurons), nucleus of the solitary
      tract (A2/C2 catecholamine neurons), lateral parabrachial nucleus, supramamillary
      nucleus, bed nucleus of the stria terminalis, accumbens core and medial
      prefrontal cortex no differences in the withdrawal treatments were detected. We
      have shown that peripheral opioid withdrawal can affect central nervous system
      pathways.

PMID- 11587713
TI  - Modulation of primary afferent-mediated neurotransmission and Fos expression by
      glutamate uptake inhibition in rat spinal neurones in vitro.
AB  - The effect of altered endogenous levels of synaptic glutamate on
      neurotransmission and synaptic dorsal horn Fos expression was determined in rat
      spinal cord in vitro. The uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylate
      (L-PDC, 1mM) was tested against dorsal root-ventral root potentials (DR-VRP),
      afferent-mediated slow dorsal horn excitatory postsynaptic potentials (DR-EPSP)
      and nociceptive afferent-induced synaptic currents (EPSCs) of substantia
      gelatinosa neurones. L-PDC reduced DR-VRP fast and slow peak amplitude and
      duration (P<0.05), slow DR-EPSP amplitude and duration (P<0.005) and EPSC
      amplitude (P<0.05). The Group II/III mGluR antagonist (RS)-alpha-cyclopropyl-4
      phosphonophenylglycine (CPPG, 100 microM) reduced L-PDC inhibition of synaptic
      potentials. The Group II antagonist (2S)-2-amino-2-(1S,2S-2-carboxycycloprop-1
      yl)-3-(xanth-9-yl)propanoic acid (LY341495, 300 nM) and the Group III antagonist
      (RS)-alpha-methylserine-O-phosphate (MSOP, 10 microM) partially reversed EPSC
      inhibition by L-PDC. The Group III agonist L(+)-2-amino-4-phosphonobutyric acid
      (L-AP4, 30 microM) mimicked CPPG-sensitive inhibitory effects of L-PDC on DR-VRP
      (P<0.001) and the slow DR-EPSP (P<0.005). L-PDC (1mM) or L-AP4 (30 microM)
      reduced afferent-evoked dorsal horn Fos expression, this effect was reversed by
      CPPG. These data suggest that increased synaptic glutamate levels may activate
      inhibitory Group II/III mGluR receptors and impact significantly on nociceptive
      neurotransmission and transcriptional adaptive responses of target neurones.

PMID- 11587714
TI  - Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide
      FF.
AB  - Proton-gated channels of the acid-sensing ion channel (ASIC) family are
      candidates for mediating the fast ionotropic transduction of extracellular
      acidification in neurons. ASIC subunits can assemble in homomeric and heteromeric
      channels with specific biophysical and pharmacological properties. Using
      heterologous expression of ASIC subunits in Xenopus oocytes, we show here that
      the biphasic response of heteromeric rat and human ASIC2A+3 subtypes to low pH is
      selectively modulated by the neuropeptide FF (NPFF) and by the related peptide
      FMRFamide. We recorded both a dramatic potentiation (up to 275%) of the amplitude
      of acid-gated human ASIC2A+3 maximal currents and a change of desensitization
      kinetics in the presence of NPFF (EC(50)=2 microM) leading to a slowly
      inactivating phenotype. These modulatory effects were not observed with the
      corresponding homomeric human ASIC2A or ASIC3 receptor subtypes. Moreover, the
      sensitivity of ASIC2A+3 receptors to extracellular protons was increased in the
      presence of NPFF (DeltapH(50)=+0.5). Our data therefore suggest that the direct
      sensitization of heteromeric proton-gated channels by endogenous neuropeptides
      might play a role in the neuronal response to noxious acidosis in sensory and
      central pathways.

PMID- 11587715
TI  - PKC regulates capsaicin-induced currents of dorsal root ganglion neurons in rats.
AB  - Capsaicin activates a non-specific cation conductance in a subset of dorsal root
      ganglion (DRG) neurons. The inward current and membrane potential of acutely
      isolated DRG neurons were examined using whole-cell patch recording methods. We
      report here that the current and voltage responses activated by capsaicin were
      markedly increased by phorbol 12-myristate 13-acetate (PMA), an activator of
      protein kinase C (PKC). The mean current, after application of 0.3 microM PMA,
      was 153.5+/-5.7% of control (n=32) in Ca(2+)-free external solution and 181.6+/
      6.8% of control (n=15) in standard external solution. Under current-clamp
      conditions, 0.3 microM PMA facilitated capsaicin-induced depolarization and
      action potential generation. Bindolylmaleimide I (BIM), a specific inhibitor of
      PKC activity, abolished the effect of PMA. In addition, capsaicin-evoked current
      was attenuated to 68.3+/-5.0% of control (n=13) by individual administration of 1
      microM BIM in standard external solution, while 0.3 microM BIM did not have this
      effect. These data suggest that PKC can directly regulate the capsaicin response
      in DRG neurons, which could increase nociceptive sensory transmission and
      contribute to hyperalgesia.

PMID- 11587716
TI  - Reduction of quantal size and inhibition of neuromuscular transmission by
      bafilomycin A.
AB  - The energy for uphill transport of neurotransmitters into synaptic vesicles is
      created by bafilomycin A- and concanamycin A-sensitive vacuolar H(+)-ATPase (V
      ATPase). Both blockers (at 0.1-5 microM) depressed twitch tension and induced
      tetanic fade of mouse diaphragm on stimulation of the phrenic nerve. Axonal
      impulse conduction and depolarization of motor endplate by exogenous
      acetylcholine were not inhibited. The IC(50)s for bafilomycin A and concanamycin
      A were 1.1+/-0.2 and 0.7+/-0.1 microM, respectively. Contractile response evoked
      by stimulation of diaphragm, muscle resting membrane potential and membrane
      resistance were not altered. V-ATPase blockers decreased quantal size and shifted
      the distribution of miniature endplate potentials (mepps) to low amplitude
      direction. The increase of mepp events in high KCl medium was suppressed
      slightly. The blockers depressed endplate potentials (epps) with IC(50)s of 0.7+/
      0.2 microM (bafilomycin A) and 0.4+/-0.1 microM (concanamycin A). On high
      frequency stimulation, the coefficient of variance and run-down of epps were
      increased. The inhibitory effects on mepps and epps were irreversible and
      augmented by nerve stimulation. The results suggest that inhibition of V-ATPase
      reduces the acetylcholine content of synaptic vesicles, leading to suppression of
      neuromuscular transmission.

PMID- 11587717
TI  - Effects of the noncompetitive NMDA receptor antagonist MK-801 on classical
      eyeblink conditioning in mice.
AB  - N-methyl-D-aspartate (NMDA) receptors are involved in synaptic plasticity and
      play a critical role in learning and memory. We investigated the effects of the
      noncompetitive NMDA receptor antagonist (+)MK-801 on classical eyeblink
      conditioning of mice, using various interstimulus intervals between the
      conditioned stimulus (CS) and unconditioned stimulus (US). A tone was used for
      the CS and a periorbital shock was used for the US. In the delay paradigm, in
      which the US coterminated with the CS or started immediately after CS offset, the
      effect of (+)MK-801 (0.1mg/kg, i.p.) was a slight impairment in the acquisition
      of the conditioned response (CR). During subsequent CS-alone trials, the
      responses of (+)MK-801-injected mice were extinguished as easily as those of
      saline-injected mice. In the trace paradigm, (+)MK-801 impaired acquisition of
      the CR with a trace interval of 250 ms more than it did with a trace interval of
      100 ms, and more than in the delay paradigm. (+)MK-801 injected after acquisition
      of 250-ms trace conditioning did not impair expression or extinction of the CR.
      These results suggest that NMDA receptors are involved in acquisition of the CR
      during longer trace interval conditioning more than during shorter trace interval
      conditioning or delay conditioning, and that their contribution to extinction is
      much smaller than their contribution to acquisition in mouse eyeblink
      conditioning.

PMID- 11587718
TI  - Forebrain muscarinic control of micturition reflex in rats.
AB  - Functional contribution of the cholinergic pathway between the frontal cortex and
      basal nucleus of Meynert to micturition reflex was investigated. Male Wistar rats
      were subjected to bilateral lesion of the basal forebrain by ibotenic acid (IA)
      injection (7.5 microg/rat on each side) (BF rats). Phosphate buffered saline
      (PBS) was injected into control rats (sham operated rats; SO rats).
      Cystometrograms were obtained from conscious BF and SO rats 7-10 days after
      IA/PBS injection. Bladder capacity (BC) of BF rats was significantly smaller than
      that of SO rats (approximately 43.7%) and was accompanied by decrease in choline
      acetyltransferase activity in the frontal cortices. Oxotremorine M, a muscarinic
      receptor agonist, increased BC in BF rats, while pirenzepine, an M1 muscarinic
      receptor antagonist, counteracted the effect of the oxotremorine M-induced
      increase in BC. Injection of oxotremorine M into the dorsal pontine tegmentum
      (DPT) reduced BC in BF and SO rats, while injection of pirenzepine had no effect
      on cystometrograms. These findings indicate that the M1 muscarinic receptor plays
      a part in the forebrain inhibitory mechanisms involved in the micturition reflex
      and that muscarinic receptor in the DPT contributes to excitatory control of
      micturition reflex.

PMID- 11587720
TI  - Depolarization effects in the human eye.
AB  - We have studied the effects of depolarization in the living human eye by using a
      spatially resolved Mueller-matrix polarimeter [Opt. Lett. 24 (1999) 64]. Results
      show that the degree of polarization for the central part of double-pass images
      is about 0.85 and 0.70 for 2 mm and 5 mm of pupil, respectively. This parameter
      decreases towards the tails of the image. In the plane of the pupil, the degree
      of polarization also depends on the analyzed area, and it has been related to the
      different components of the light coming back from the retina. Values of
      polarizance suggest that the eye presents a slight polarizing power mainly due to
      the existence of both circular birefringence and dichroic properties. Polarizance
      is also larger at the central part of double-pass images (about 0.25 on average)
      and decreases along the radius. In addition, it has been shown that the major
      retinal layer where the light is reflected does not depend on the state of
      polarization of the incident light.

PMID- 11587719
TI  - GABAergic and NPY-Y(1) network in the medial amygdala: a neuroanatomical basis
      for their functional interaction.
AB  - We used Y(1)R/LacZ transgenic mice to investigate the interaction between NPY,
      GABA and Y(1) receptors in the amygdala. Immunolabeling of GABA and NPY positive
      neurons and histochemical staining of beta-galactosidase revealed NPY and GABA
      colocalization and close contacts of NPY-positive fibers with GABAergic neurons
      also expressing the Y(1)R/LacZ transgene.

PMID- 11587721
TI  - Spatial scale of motion segmentation from speed cues.
AB  - For the accurate perception of multiple, potentially overlapping, surfaces or
      objects, the visual system must distinguish different local motion vectors and
      selectively integrate similar motion vectors over space to segment the retinal
      image properly. We recently showed that large differences in speed are required
      to yield a percept of motion transparency. In the present study, to investigate
      the spatial scale of motion segmentation from speed cues alone, we measured the
      speed-segmentation threshold (the minimum speed difference required for 75%
      performance accuracy) for 'corrugated' random-dot patterns, i.e. patterns in
      which dots with two different speeds were alternately placed in adjacent bars of
      variable width. In a first experiment, we found that, at large bar widths, a
      smaller speed difference was required to segment and perceive the corrugated
      pattern of moving dots, while at small bar-widths, a larger speed difference was
      required to segment the two speeds and perceive two transparent surfaces of
      moving dots. Both the perceptual and segmentation performance transitions
      occurred at a bar width of around 0.4 degrees. In a second experiment, speed
      segmentation thresholds were found to increase sharply when dots with different
      speeds were paired within a local pooling area. The critical pairing distance was
      about 0.2 degrees in the fovea and increased linearly with stimulus eccentricity.
      However, across the range of eccentricities tested (up to 15 degrees ), the
      critical pairing distance did not change much and remained close to the receptive
      field size of neurons within the primate primary visual cortex. In a third
      experiment, increasing dot density changed the relationship between speed
      segmentation thresholds and bar width. Thresholds decreased for large bar widths,
      but increased for small bar widths. All of these results are well fit by a simple
      stochastic model, which estimates the probabilities of having identical or
      different motion vectors within a local pooling area whose size is the same as
      that of primate V1 neurons. Altogether, these results demonstrate that speed
      based segmentation can function well, even at small spatial scales (i.e. high
      spatial frequencies of spatial corrugation) and thereby emphasizes the critical
      role of a local pooling process early in the cortical motion-processing pathway.

PMID- 11587722
TI  - Segmentation in structure from motion: modeling and psychophysics.
AB  - Much work has been done on the question of how the visual system extracts the
      three-dimensional (3D) structure and motion of an object from two-dimensional
      (2D) motion information, a problem known as 'Structure from Motion', or SFM. Much
      less is known, however, about the human ability to recover structure and motion
      when the optic flow field arises from multiple objects, although observations of
      this ability date as early as Ullman's well-known two-cylinders stimulus [The
      interpretation of visual motion (1979)]. In the presence of multiple objects, the
      SFM problem is further aggravated by the need to solve the segmentation problem,
      i.e. deciding which motion signal belongs to which object. Here, we present a
      model for how the human visual system solves the combined SFM and segmentation
      problems, which we term SSFM, concurrently. The model is based on computation of
      a simple scalar property of the optic flow field known as def, which was
      previously shown to be used by human observers in SFM. The def values of many
      triplets of moving dots are computed, and the identification of multiple objects
      the image is based on detecting multiple peaks in the histogram of def values. In
      five experiments, we show that human SSFM performance is consistent with the
      predictions of the model. We compare the predictions of our model to those of
      other theoretical approaches, in particular those that use a rigidity hypothesis,
      and discuss the validity of each approach as a model for human SSFM.

PMID- 11587723
TI  - 3D after-effects are due to shape and not disparity adaptation.
AB  - There are a variety of stereoscopic after-effects in which exposure to a stimulus
      with a particular slant or curvature affects the perceived slant or curvature of
      a subsequently presented stimulus. These after-effects have been explained as a
      consequence of fatigue (a decrease in responsiveness) among neural mechanisms
      that are tuned to particular disparities or patterns of disparity. In fact, a
      given disparity pattern is consistent with numerous slants or curvatures; to
      determine slant or curvature, the visual system must take the viewing distance
      into account. We took advantage of this property to examine whether the
      mechanisms underlying the stereoscopic curvature after-effect are tuned to
      particular disparity patterns or to some other property such as surface
      curvature. The results clearly support the second hypothesis. Thus, 3D after
      effects appear to be caused by adaptation among mechanisms specifying surface
      shape rather than among mechanisms signaling the disparity pattern.

PMID- 11587724
TI  - Transducer models of head-centred motion perception.
AB  - By adding retinal and pursuit eye-movement velocity one can determine the motion
      of an object with respect to the head. It would seem likely that the visual
      system carries out a similar computation by summing extra-retinal, eye-velocity
      signals with retinal motion signals. Perceived head-centred motion may therefore
      be determined by differences in the way these signals encode speed. For example,
      if extra-retinal signals provide the lower estimate of speed then moving objects
      will appear slower when pursued (Aubert-Fleischl phenomenon) and stationary
      objects will move opposite to an eye movement (Filehne illusion). Most previous
      work proposes that these illusions exist because retinal signals encode retinal
      motion accurately while extra-retinal signals under-estimate eye speed. A more
      general model is presented in which both signals could be in error. Two types of
      input/output speed relationship are examined. The first uses linear speed
      transducers and the second non-linear speed transducers, the latter based on
      power laws. It is shown that studies of the Aubert-Fleischl phenomenon and
      Filehne illusion reveal the gain ratio or power ratio alone. We also consider
      general velocity-matching and show that in theory matching functions are limited
      by gain ratio in the linear case. However, in the non-linear case individual
      transducer shapes are revealed albeit up to an unknown scaling factor. The
      experiments show that the Aubert-Fleischl phenomenon and Filehne illusion are
      adequately described by linear speed transducers with a gain ratio less than one.
      For some observers, this is also the case in general velocity-matching
      experiments. For other observers, however, behaviour is non-linear and, according
      to the transducer model, indicates the existence of expansive non-linearities in
      speed encoding. This surprising result is discussed in relation to other theories
      of head-centred motion perception and the possible strategies some observers
      might adopt when judging stimulus motion during an eye movement.

PMID- 11587725
TI  - Peripheral and parafoveal cueing and masking effects on saccadic selectivity in a
      gaze-contingent window paradigm.
AB  - The present study employed the gaze-contingent window paradigm to investigate
      parafoveal and peripheral cueing and masking effects on saccadic selectivity in a
      triple-conjunction visual search task. In the cueing conditions, the information
      shown outside the gaze-contingent window was restricted to the feature or feature
      pair shared between the target and a particular distractor type. In the masking
      conditions, no stimulus features were shown outside the window. Significant
      cueing and masking effects on saccadic selectivity were observed for saccades
      directed at items within the window, where all features were visible across
      experimental conditions. Cueing a particular feature or feature pair biased
      saccadic selectivity towards this feature or feature pair, while masking
      generally reduced saccadic selectivity. These findings support the concept of
      visual guidance being a preattentive process that operates in parallel across the
      display.

PMID- 11587726
TI  - Linear mechanisms can produce motion sharpening.
AB  - Human observers are not normally conscious of blur from moving objects [Nature
      284 (1980) 164]. Several recent reports have even shown that blurred images
      appear sharper when drifting than when stationary and have suggested different
      non-linear mechanisms to explain this phenomenon [Vision Res. 36 (1996) 2729;
      Vision Res. 38 (1998) 2099]. We demonstrate here that even though distortions of
      drifting narrow-band sine-wave gratings cannot be explained by linear mechanisms,
      these mechanisms may have an important role in sharpening of moving edges. We
      show first that the effective spatial filter for a moving object that is formed
      by a simple difference-of-Gaussians spatial filter and the typical biphasic
      temporal impulse response function can be approximated by a combination of
      Gaussian filters only. When this filter is applied to moving, Gaussian-blurred
      edges, regions of blurring and sharpening are found over the same ranges of blur
      widths and velocities where recent experimental findings have shown them to
      exist. In general, that means that the output of the filter shows blurring in
      response to small blur widths and sharpening in response to larger blur widths.

PMID- 11587727
TI  - Augmented rod bipolar cell function in partial receptor loss: an ERG study in
      P23H rhodopsin transgenic and aging normal rats.
AB  - Physiological consequences of early stages of photoreceptor degeneration were
      examined in heterozygous P23H rhodopsin transgenic (Tg) and in aging normal
      Sprague-Dawley rats. Rod photoreceptor and rod bipolar (RB) cell function were
      estimated with maximum value and sensitivity parameters of P3 and P2 components
      of the electroretinogram. In both Tg and aging normal rats, the age-related rate
      of decline of P3 amplitude was steeper than that of the P2 amplitude. Tg rats
      showed greater than normal sensitivity of the rods. A new model of distal RB
      pathway connectivity suggested photoreceptor loss could not be the sole cause of
      physiological abnormalities; there was an additional increase of post-receptoral
      sensitivity. We propose that changes at rod-RB synapses compensate for the
      partial loss of rod photoreceptors in senescence and in early stages of retinal
      degeneration.

PMID- 11587728
TI  - A longitudinal study of the biometric and refractive changes in full-term infants
      during the first year of life.
AB  - Changes in ocular axial dimensions and refraction were followed longitudinally,
      using ultrasonography and retinoscopy, during the first year of life (mean ages 4
      53 weeks) of a group of 20 full-term infants (10 male, 10 female). Using a mixed
      model regression analysis, axial length changes as a function of time were found
      to be best described by a quadratic expression (AL=17.190+0.128x-0.0013x(2),
      where AL is the axial length in mm and x is the age in weeks), while anterior
      chamber depth changed linearly (ACD=2.619+0.018x, where ACD is the anterior
      chamber depth in mm): lens thickness was essentially constant. Spherical
      equivalent refraction through most of the first year showed a steady reduction in
      hypermetropia (SER=2.982-0.032x, where SER is the spherical equivalent refraction
      in dioptres): astigmatism also tended to diminish. Mean hyperopic refractive
      errors through the year were negatively correlated with corresponding axial
      lengths (SER=12.583-0.541AL), but some individual subjects showed marked
      departures from this pattern. These results are discussed in relation to concepts
      of emmetropization.

PMID- 11587730
TI  - Establishment and characterisation of ovine blood monocyte-derived cell lines.
AB  - Studies of the important functions in host defense assured by macrophages, both
      as functional elements and as potential targets for intracellular pathogens, are
      often inhibited by the lack of a source of large numbers of uniform, well
      characterised cells. To address this lack for ovine studies, we have established
      cell lines from spontaneously-proliferating adherent mononuclear cells from sheep
      blood. Eight such lines which have been continuously cultured for over 400
      passages have phagocytic activities and cytochemical characteristics indicating
      that they retain the nature of mononuclear phagocytes. They display typical
      functional membrane proteins such as CD14, Fc receptors and MHC class II. Such
      cells can facilitate in vitro studies of pathogen-monocyte interactions and can
      furnish copious amounts of cells for transfer experiments.

PMID- 11587731
TI  - Isolation, characterisation and expression of mRNAs encoding the ovine CC
      chemokines, monocyte chemoattractant protein (MCP)-1alpha and -2.
AB  - CC chemokines are important mediators of immune responses, orchestrating the
      differential recruitment of various leukocyte populations. Despite the large
      number of known CC chemokines in other species, no cDNA encoding ovine CC
      chemokines have been isolated. A homology cloning strategy was utilised to
      isolate the cDNA of ovine CC chemokines. Full-length monocyte chemoattractant
      protein (MCP)-1alpha and -2 cDNA have been isolated. The predicted ovine MCP
      1alpha amino acid sequence shares 87 and 75% identity with bovine MCP-1alpha and
      porcine MCP-1, respectively. The predicted ovine MCP-2 amino acid sequence shares
      92 and 85% identity with bovine and porcine MCP-2, respectively. Northern blot
      analysis of MCP-1alpha revealed that it is strongly expressed in cells isolated
      from mammary lavage fluid (MAL) of ewes given intramammary infusions of
      Haemonchus contortus. Weak signals were detected in mammary and abomasal tissue.
      Southern blot analysis of reverse transcriptase-polymerase chain reaction (RT
      PCR) products indicates that MCP-1alpha mRNA levels increase in abomasum after
      challenge with H. contortus. MCP-1alpha mRNA levels were also increased in
      bronchoalveolar lavage (BAL) cells and lung tissue after house dust mite extract
      (HDME) challenge. Similarly, MCP-2 mRNA was detected by Northern blot analysis at
      high levels in MAL cells after H. contortus intramammary infusion, and increased
      in BAL cells and lung tissue in HDME-challenged sheep. MCP-2 mRNA was not
      detected by Northern blots in whole mammary or abomasal tissue, but Southern blot
      analysis of RT-PCR products also indicates that MCP-2 mRNA increases in abomasal
      tissue after challenge with H. contortus. Hence, two ovine CC chemokine mRNA have
      been isolated that are up-regulated in response to parasite infection and
      allergen challenge. Ultimately the isolation of these and other ovine CC
      chemokines will help elucidate a wide variety of immune responses in sheep.

PMID- 11587732
TI  - Polyclonal activation of B cells occurs in lymphoid organs from porcine
      reproductive and respiratory syndrome virus (PRRSV)-infected pigs.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) induces a persistent
      viral infection associated with an inefficient humoral immune response. A study
      of lymphoid B cells and specific humoral immune response was performed in blood
      and several lymphoid organs collected from PRRSV experimentally-infected pigs.
      Groups of specific pathogen-free (SPF) pigs were infected with the LHVA-93-3
      isolate of PRRSV, and blood, tonsils, spleen and mediastinal lymph nodes (MLN)
      were collected at various times postinfection (p.i.) (3-60 days). Lymphoid cells
      were isolated, immunolabeled for cytofluorometric determination of B cell
      percentages, used for counting specific anti-PRRSV antibody secreting B cells by
      an ELISPOT assay, or cultured for metabolic activity. The presence of anti-PRRSV
      antibodies in the serum of infected pigs was determined using a commercial ELISA
      assay. Virus detection was performed in all tissues, including lungs, by virus
      isolation and RT-PCR. The results show that percentages of B cells increased in
      tonsils as soon as 3 days until 17 days p.i. in PRRSV-infected pigs while they
      increased in spleen at 3 days p.i. only, due to an increase of larger Ig(high)
      producing B cells. Metabolic activity of lymphoid cells from blood and spleen
      increased at 3 days p.i. only while lymphoid cells from tonsils and MLN
      transiently decreased at that time and increased thereafter up to 60 days p.i.
      Anti-PRRSV antibody-secreting B cells occurred in tonsils after 10 days p.i. and
      strongly increased up to 60 days p.i. However, specific anti-PRRSV-secreting B
      cells were detected in blood and spleen after 17 days p.i and in MLN only after
      45 days p.i. Specific antibodies were detectable in serum at 10 days p.i.,
      reached the maximum level at 45 days and remained high up to 60 days p.i.
      Infectious virus was detected in lungs and MLN as soon as 3 days p.i., and
      remained detectable up to 45 days p.i. in tonsils of one pig while viral RNA was
      detected in most organs up to 60 days p.i. In vitro experiments revealed that
      inactivated virus induced a stimulation of lymphoid cells isolated from PRRSV
      infected pigs while it was cytotoxic for lymphoid cells from control pigs. Taken
      together, these results indicate that viral infection induced simultaneously a
      polyclonal activation of B cells, mainly in tonsils, and an exaggerated and
      prolonged specific humoral immune response due to persistent viral infection in
      lymphoid organs.

PMID- 11587734
TI  - Nucleotide sequence and restriction fragment length polymorphisms of the equine
      Cvarepsilon gene.
AB  - IgE is the dominant immunoglobulin isotype involved in type I hypersensitivities
      in mammals. The heavy chain constant region domains of equine IgE are encoded by
      a single gene, the Cvarepsilon gene. By restriction analysis of cDNA from 15
      unrelated horses, we have now identified two Cvarepsilon alleles, characterised
      by a Sma I restriction fragment length polymorphism, which we designated
      Cvarepsilon(a) and Cvarepsilon(b). Sequence analysis of both, Cvarepsilon(a) and
      Cvarepsilon(b) cDNA, showed in addition two single base exchanges resulting in
      two amino acid substitutions. Both sequences have only 95.9% homology of the
      coding region sequence with the published equine Cvarepsilon sequence, which
      could represent a third haplotype. Polymorphism of the IgE heavy chain constant
      region gene, as described here, might well impose genetic variability on the
      effector functions of equine IgE predisposition to allergic diseases in horses.

PMID- 11587733
TI  - Molecular cloning and functional characterization of bottlenose dolphin (Tursiops
      truncatus) tumor necrosis factor alpha.
AB  - Bottlenose dolphin tumor necrosis factor alpha (doTNF-alpha) cDNA was cloned by
      reverse transcription polymerase chain reaction (RT-PCR) and the nucleic and
      deduced amino acid sequences were determined. The sequence of the cDNA clones
      shows that doTNF-alpha has an open reading frame of 699bp encoding 233 amino
      acids. The nucleic acid sequence of doTNF-alpha indicates 90, 88, 87, and 79%
      similarity with the cattle, pig, human, and mouse TNF-alpha gene, respectively.
      Based on the analysis of human and mouse TNF-alpha molecules, doTNF-alpha is
      processed to a mature protein with 157 amino acids. The 233 amino acids precursor
      has a hydrophobic region that could serve as a transmembrane domain. The
      recombinant doTNF-alpha expressed in Escherichia coli as a glutathione S
      transferase fusion protein reacted with anti-human TNF-alpha antibody and exerted
      cytotoxity to the TNF-alpha sensitive murine cell line L929.

PMID- 11587735
TI  - Cannabinoids inhibit nitric oxide production in bone marrow derived feline
      macrophages.
AB  - Feline immunodeficiency virus (FIV) infection causes a widespread natural
      immunodeficiency syndrome in cats that is considered a suitable animal model for
      studying human immunodeficiency virus (HIV) infection and pathogenesis. Short
      term cultures of bone marrow derived feline macrophages stimulated with
      recombinant feline interferon-gamma (r-IFN-gamma) and lipopolysaccharide (LPS)
      were shown to produce nitric oxide. Feline macrophages were shown to express
      cannabinoid receptors, and nitric oxide production decreased after in vitro
      exposure to synthetic cannabinoid CP-55940. Both cannabinoid receptors, CB1 and
      CB2, were involved in this process, since the inhibition was reversed by
      selective cannabinoid antagonists for both of these receptors.

PMID- 11587736
TI  - Production and characterization of monoclonal antibodies reactive with the
      chicken interleukin-15 receptor alpha chain.
AB  - We recently cloned the genes encoding chicken IL-15 and IL-15 receptor (R) alpha
      proteins. In this study, 12 monoclonal antibodies (mAbs) against recombinant
      chicken IL-15Ralpha were produced and characterized. By enzyme-linked
      immunosorbent assay (ELISA), all mAbs showed binding specificity for IL-15Ralpha,
      but not IL-2 or interferon-gamma, and identified a 25.0kDa protein by immunoblot
      analysis. Flow cytometric analysis revealed negligible expression of IL-15Ralpha
      on non-activated lymphocytes from the spleen, thymus or bursa, low but detectable
      expression on macrophages and high expression on concanavalin A-activated spleen
      lymphoblasts. Established chicken T cell (RP13) and macrophage (HD11) cell lines
      expressed substantially higher levels of IL-15Ralpha compared with a B cell line
      (RP9). Two mAbs inhibited IL-15 dependent proliferation of T cells suggesting
      that the tertiary structure of the protein domain of native IL-15Ralpha that
      binds to IL-15 is preserved in the recombinant receptor molecule. These mAbs will
      be useful reagents for further in vitro and in vivo studies of the biological
      functions of chicken IL-15 and its receptor.

PMID- 11587737
TI  - Molecular, cellular, and functional characterization of chicken cytokines
      homologous to mammalian IL-15 and IL-2.
AB  - DNA sequence analysis of a chicken interleukin (IL)-15 cDNA identified a 187
      amino acid open reading frame encoding a protein with a predicted molecular
      weight of 21,964Da, two potential N-linked glycosylation sites, four highly
      conserved Cys residues, two out-of-frame AUG initiation codons in the 5'
      untranslated region, and an unusually long (66 amino acid) signal peptide such
      that the expected size of the mature protein is 14,462Da. Chicken IL-15 and IL-2
      were compared with regard to their molecular, cellular, and functional
      characteristics. The predicted amino acid sequences of both chicken cytokines
      showed greater homologies with mammalian IL-15s compared with mammalian IL-2s.
      Northern hybridization and RT-PCR demonstrated chicken IL-15 gene transcripts in
      a wide variety of tissues and cell types while the chicken IL-2 gene was
      expressed only in concanavalin A (con A)-activated spleen cells. Both recombinant
      cytokines stimulated the growth of spleen T-cells and enhanced the activity of
      natural killer (NK) cells in vitro. Subcutaneous injection with an expression
      plasmid encoding IL-15 increased the percentage of CD3+ spleen T-lymphocytes
      whereas injection of an IL-2 cDNA augmented CD3+, CD4+, CD8+, T-cell receptor
      (TCR)1+, and TCR2+ T-cells. Collectively, these results indicate that chicken IL
      15 and IL-2 are T-cell growth factors potentially capable of enhancing cell
      mediated immunity in vivo.

PMID- 11587738
TI  - Immunohistological study of the immune system cells in paraffin-embedded tissues
      of conventional pigs.
AB  - The distribution of different cells of the immune system has been studied in
      formalin-fixed paraffin-embedded tissues from conventionally reared healthy pigs,
      using immunohistological techniques. The samples collected were: lungs, tonsils,
      lymph nodes (mediastinal, mesenteric, inguinal and submandibular), pancreas,
      spleen, liver, kidney, adrenal gland, ileum and stomach. A total of six primary
      antibodies anti-CD3, anti-CD79alpha, Mac 387, anti-lysozyme, anti-CD45RA (3C3/9)
      and anti-SLA-II-DQ (BL2H5) were used with a standard avidin-biotin peroxidase
      (ABC) method. Anti-CD3 and anti-CD79alpha mAb-reacted, respectively with cells
      located in T cell areas and B cell areas. Mac 387 recognised circulating
      polymorphonuclear leukocytes, while anti-lysozyme-stained resident macrophages in
      all tissues. 3C3/9 and BL2H5, were assessed in formalin-fixed paraffin-embedded
      tissues for the first time. 3C3/9 identified B lymphocytes, in primary follicles
      and mantle zones, a subpopulation of T cells, especially located in the marginal
      zone of the spleen and a variable number of immunoblasts, in the germinal
      centres. BL2H5 reacted with B cells in the mantle zones of the follicles of
      lymphoid tissues, with dendritic and interdigitating cells in all studied
      lymphoid tissues and with a variable number of resting and activated T cells in
      the periarteriolar lymphoid sheath (PALs), marginal zone and red pulp of the
      spleen. Furthermore, it stained Kupffer and perivascular macrophages in the
      liver. This study represents a detailed histological study of the distribution of
      the most important subpopulations of immune system cells in conventional, healthy
      pigs. In our view, these tools should be useful for future comparative studies in
      disease conditions.

PMID- 11587739
TI  - Cytokine gene expression in lymph node and spleen of sheep in response to
      Salmonella infection by two serotypes displaying different host specificity.
AB  - In order to investigate the determinism of the host specificity and to better
      understand the host resistance mechanisms, infections of sheep were performed
      with either S. abortusovis, serotype specific for ovine species, or with S.
      dublin, serotype adapted to cattle and accidentally transmissible to human.
      Following a subcutaneous challenge, S. dublin disseminated more rapidly towards
      lymphoid tissues than S. abortusovis. However, S. abortusovis tended to persist
      in spleen more efficiently than S. dublin. Using a quantitative RT-PCR method,
      the expression level of ovine cytokines genes was measured in the draining lymph
      node and in the spleen, in the course of infection. Inflammatory cytokine
      response was characterised by an early and strong increase of IL-1beta and
      TNFalpha mRNA in both lymphoid organs following S. dublin infection, while S.
      abortusovis challenge only induced IL-1beta mRNA increase in the spleen at day 3
      post-inoculation. Likewise, S. dublin infection provoked a marked increase of IL
      12 mRNA and a slight up-regulation of IFNgamma gene transcription in the local
      lymphoid site, in contrast to S. abortusovis infection. Elsewhere, both serotypes
      induced a strong and early IL-10 mRNA production and had no effect on IL-4 gene
      expression. Finally, taken together, these data suggest that the intensity of
      inflammatory and anti-infectious cytokine responses, but not the type 2 cytokine
      response, is serotype-dependent. They also suggest that the host-specific
      serotype, by limiting the host cytokine-mediated defence, could favour its
      persistence within lymphoid organs.

PMID- 11587740
TI  - Peripheral blood mononuclear cell responses to Dermatophagoides farinae in canine
      atopic dermatitis.
AB  - Atopic dermatitis is a chronic inflammatory and pruritic skin disease commonly
      seen in dogs and humans that is characterised by the presence of allergen
      specific IgE. Data from skin tests and serological analysis suggest that the
      house dust mite Dermatophagoides farinae is the most important allergen in dogs
      with atopic dermatitis. The aim of this study was to determine if D. farinae
      specific peripheral blood mononuclear cell (PBMC) responses could be detected in
      dogs with atopic dermatitis. PBMCs were isolated by the density centrifugation
      from dogs with atopic dermatitis that were skin test positive for D. farinae,
      dogs with atopic dermatitis that were skin test negative for D. farinae, and
      healthy dogs. Cells were cultured with increasing concentrations of the D.
      farinae extract, no antigen, vaccine antigens or concanavalin A (ConA). There was
      significantly greater responsiveness of PBMCs from the D. farinae positive dogs
      than from either the D. farinae negative or healthy dogs (ANOVA, P<0.05). In
      contrast, no significant differences were observed in the control responses
      between the three groups. This is the first study to demonstrate that D. farinae
      specific circulating memory cells are involved in the pathogenesis of canine
      house dust mite hypersensitivity.

PMID- 11587741
TI  - How antigenic peptides are made to fit their groove.

PMID- 11587764
TI  - The 'biodrug' concept: an innovative approach to therapy.
AB  - Cell engineering technology using recombinant microorganisms has created new
      opportunities in the development of innovative drugs. This article presents the
      use of living genetically engineered microorganisms, such as bacteria or yeasts,
      as a new delivery vehicle to the gastrointestinal tract. This 'biodrug' concept
      was demonstrated using recombinant Saccharomyces cerevisiae expressing the plant
      cytochrome P450 73A1. This enzyme provides a relevant model for potential
      therapeutic applications, such as 'biodetoxication' in the digestive environment.
      An artificial gastrointestinal tract simulating human digestion was chosen as a
      powerful tool to validate the biodrug concept. This approach offers a novel
      strategy for drug discovery and testing.

PMID- 11587765
TI  - The Virtual Cell: a software environment for computational cell biology.
AB  - The newly emerging field of computational cell biology requires software tools
      that address the needs of a broad community of scientists. Cell biological
      processes are controlled by an interacting set of biochemical and
      electrophysiological events that are distributed within complex cellular
      structures. Computational modeling is familiar to researchers in fields such as
      molecular structure, neurobiology and metabolic pathway engineering, and is
      rapidly emerging in the area of gene expression. Although some of these
      established modeling approaches can be adapted to address problems of interest to
      cell biologists, relatively few software development efforts have been directed
      at the field as a whole. The Virtual Cell is a computational environment designed
      for cell biologists as well as for mathematical biologists and bioengineers. It
      serves to aid the construction of cell biological models and the generation of
      simulations from them. The system enables the formulation of both compartmental
      and spatial models, the latter with either idealized or experimentally derived
      geometries of one, two or three dimensions.

PMID- 11587766
TI  - RNase P: from biological function to biotechnological applications.
AB  - The M1 RNA subunit of Escherichia coli RNase P is a ribozyme responsible for the
      catalytic activity of the complex. It removes the 5' leader sequence from tRNA
      precursors to form mature tRNAs. M1 recognizes its target mainly on the basis of
      its structure and this allows the design of modified ribozymes engineered to
      destroy other molecules without the need for special sequences in the targeted
      mRNAs. M1 is thus an ideal tool to eliminate the tumourigenic chimeric messengers
      created after chromosomal translocations. These results have direct implications
      for cancer therapeutics and molecular biology in general.

PMID- 11587767
TI  - Gene expression microarrays and the integration of biological knowledge.
AB  - Large-scale parallel measurement of whole-genome RNA expression is now possible
      with high-density arrays of cDNA or oligonucleotides. Using this technology
      efficiently will require the integration of other sources of biological
      information, such as gene identity, biomedical literature and biochemical pathway
      for a given gene. Such integration is essential to understand the cellular
      program of gene expression and the molecular physiology of an organism. Advances
      in microarray technology, and the expected rapid rise in microarray data will
      lead to new insight into fundamental biological problems such as the prediction
      of gene function from expression profiles and the identification of potential
      drug targets from biologically active compounds.

PMID- 11587768
TI  - Structural insights into the mechanical regulation of molecular recognition
      sites.
AB  - Intriguing experimental and computational data are emerging to suggest that
      mechanical forces regulate the functional states of some proteins by stretching
      them into nonequilibrium states. Using the extracellular matrix protein
      fibronectin as an example, we discuss molecular design principles that might
      control the exposure of a protein's recognition sites, and/or their relative
      distances, in a force-dependent manner. Fibronectin regulates many cellular
      functions by binding directly to integrins. Although integrins have a key role in
      the transduction of force across the cell membrane by coupling the extracellular
      matrix to the cytoskeleton, the studies reviewed here suggest that fibronectin
      might be one of the molecules responsible for the initial transformation of
      mechanical force into a biochemical signal.

PMID- 11587769
TI  - What makes genetically modified organisms so distasteful?
AB  - The debate concerning genetically modified organisms goes on unabated and
      reflects some genuine concerns. I suggest that a significantly large number of
      educated people believe that moving genes around between species is intuitively
      wrong and that this is based on an essentialist view of the world. This
      essentialist view has a long history that dates back to Plato and Aristotle and
      was eventually overthrown by the population thinking of Charles Darwin. The
      essentialist, who is antipathetic to population thinking, will naturally find the
      transfer of a gene from one organism to another distasteful, and this, I argue,
      is the result of Platonic thinking, which still remains and casts its spell over
      us today.

PMID- 11587770
TI  - Integrative psychophysiology.
AB  - This paper attempts to provide an overview of the current status and some
      possible future directions of 'Integrative Psychophysiology'. Exemplar
      integrations are offered for: (i) the theory of some of the more cited models of
      the brain as a system; (ii) a numerical simulation of brain dynamics
      (highlighting the plausibility of exploring mechanisms at the whole brain scale);
      and (iii) an empirical profile of disturbances in patients with schizophrenia
      (reflecting a prototypical disorder of overall brain instability and suboptimal
      integrative information processing). These 'integrative' dimensions provide a
      frame of reference for considering interrelationships among brain dynamics and
      behaviour, in health and disease.

PMID- 11587771
TI  - The event-related optical signal: a new tool for studying brain function.
AB  - This paper presents an overview of a new method for the non-invasive measurement
      of brain function, the event-related optical signal (EROS). This technique is
      based on measures of the optical properties of cortical brain tissue, which
      change while the tissue is active. These changes are likely to be due to changes
      in light scattering, and are very rapid and localized, being related to phenomena
      occurring within or around the neuronal membrane. EROS, therefore yields images
      of cortical activity that combine spatial specificity (i.e. they can be related
      to patches of tissue less than a cubic centimeter in size) with temporal
      resolution (i.e. they depict the time course of the neural activity in the
      cortical areas under measurement). A limitation of this technique is its reduced
      penetration into the head (less than 3-5 cm). EROS appears to be a suitable
      technique for studying the time course of activity in selected cortical areas,
      and for providing a bridge between hemodynamic and electrophysiological imaging
      methods.

PMID- 11587772
TI  - The polyvagal theory: phylogenetic substrates of a social nervous system.
AB  - The evolution of the autonomic nervous system provides an organizing principle to
      interpret the adaptive significance of physiological responses in promoting
      social behavior. According to the polyvagal theory, the well-documented
      phylogenetic shift in neural regulation of the autonomic nervous system passes
      through three global stages, each with an associated behavioral strategy. The
      first stage is characterized by a primitive unmyelinated visceral vagus that
      fosters digestion and responds to threat by depressing metabolic activity.
      Behaviorally, the first stage is associated with immobilization behaviors. The
      second stage is characterized by the sympathetic nervous system that is capable
      of increasing metabolic output and inhibiting the visceral vagus to foster
      mobilization behaviors necessary for 'fight or flight'. The third stage, unique
      to mammals, is characterized by a myelinated vagus that can rapidly regulate
      cardiac output to foster engagement and disengagement with the environment. The
      mammalian vagus is neuroanatomically linked to the cranial nerves that regulate
      social engagement via facial expression and vocalization. As the autonomic
      nervous system changed through the process of evolution, so did the interplay
      between the autonomic nervous system and the other physiological systems that
      respond to stress, including the cortex, the hypothalamic-pituitary-adrenal axis,
      the neuropeptides of oxytocin and vasopressin, and the immune system. From this
      phylogenetic orientation, the polyvagal theory proposes a biological basis for
      social behavior and an intervention strategy to enhance positive social behavior.

PMID- 11587773
TI  - New perspectives in EEG/MEG brain mapping and PET/fMRI neuroimaging of human
      pain.
AB  - With the maturation of EEG/MEG brain mapping and PET/fMRI neuroimaging in the
      1990s, greater understanding of pain processing in the brain now elucidates and
      may even challenge the classical theory of pain mechanisms. This review scans
      across the cultural diversity of pain expression and modulation in man. It
      outlines the difficulties in defining and studying human pain. It then focuses on
      methods of studying the brain in experimental and clinical pain, the cohesive
      results of brain mapping and neuroimaging of noxious perception, the implication
      of pain research in understanding human consciousness and the relevance to
      clinical care as well as to the basic science of human psychophysiology. Non
      invasive brain studies in man start to unveil the age-old puzzles of pain
      illusion, hypnosis and placebo in pain modulation. The neurophysiological and
      neurohemodynamic brain measures of experimental pain can now largely satisfy the
      psychophysiologist's dream, unimaginable only a few years ago, of modelling the
      body-brain, brain-mind, mind-matter duality in an inter-linking 3-P triad:
      physics (stimulus energy); physiology (brain activities); and psyche
      (perception). For neuropsychophysiology greater challenges lie ahead: (a) how to
      integrate a cohesive theory of human pain in the brain; (b) what levels of
      analyses are necessary and sufficient; (c) what constitutes the structural
      organisation of the pain matrix; (d) what are the modes of processing among and
      across the sites of these structures; and (e) how can neural computation of these
      processes in the brain be carried out? We may envision that modular
      identification and delineation of the arousal-attention, emotion-motivation and
      perception-cognition neural networks of pain processing in the brain will also
      lead to deeper understanding of the human mind. Two foreseeable impacts on
      clinical sciences and basic theories from brain mapping/neuroimaging are the
      plausible central origin in persistent pain and integration of sensory-motor
      function in pain perception.

PMID- 11587774
TI  - Cortical network dynamics during verbal working memory function.
AB  - This study is an exploratory investigation of the regional timing of cortical
      activity associated with verbal working memory function. ERP activity was
      obtained from a single subject using a 124-channel sensor array during a task
      requiring the monitoring of imageable words for occasional targets. Distributed
      cortical activity was estimated every 2.5 ms with high spatial resolution using
      real head, boundary element modelling of non-target activity. High-resolution
      structural MRI was used for segmentation of tissue boundaries and co-registration
      to the scalp electrode array. The inverse solution was constrained to the
      cortical surface. Cortical activity was observed in regions commonly associated
      with verbal working memory function. This included: the occipital pole (early
      visual processing); the superior temporal and inferior parietal gyrus bilaterally
      and the left angular gyrus (visual and phonological word processing); the dorsal
      lateral occipital gyrus (spatial processing); and aspects of the bilateral
      superior parietal lobe (imagery and episodic verbal memory). Activity was also
      observed in lateral and superior prefrontal regions associated with working
      memory control of sensorimotor processes. The pattern of cortical activity was
      relatively stable over time, with variations in the extent and amplitude of
      contributing local source activations. By contrast, the pattern of concomitant
      scalp topography varied considerably over time, reflecting the linear summation
      effects of volume conduction that often confound dipolar source modelling.

PMID- 11587775
TI  - What has MMN revealed about the auditory system in schizophrenia?
AB  - Evidence that deficits in early auditory processing occur in schizophrenia was
      first provided by an ERP study demonstrating that mismatch negativity (MMN) to
      duration increments is reduced in medicated patients. Our subsequent research,
      which is reviewed in this paper, demonstrates that duration MMN reduction cannot
      be attributed to neuroleptic medication, and is specific to schizophrenia. It is
      not dependent upon the nature of the task used to distract attention away from
      the auditory modality. Most importantly, a reduced duration MMN in schizophrenia
      is a replicable result, having been observed in multiple independently-selected
      groups of patients from two separate laboratories. It also occurs in unaffected
      first-degree relatives of patients, suggesting that it may be a vulnerability
      marker of the disorder. The most intriguing questions however, relate to what
      underpins the reduced MMN to duration increments in schizophrenia and therefore,
      what it reveals about the nature of the auditory system deficit in this disorder.
      Three hypotheses are considered here: a pervasive problem in auditory sensory
      memory; a specific impairment in duration processing; or an abnormality within
      the window of temporal integration, coincident with the early phase of auditory
      sensory memory. Our data so far offer preliminary support for the third
      hypothesis only, although the possibility of a more broadly defined deficit in
      temporal processing restricted to brief or rapidly-presented auditory stimuli is
      canvassed.

PMID- 11587776
TI  - Sex differences in brain and behavior: emphasis on nicotine, nitric oxide and
      place learning.
AB  - Although males and females are unmistakably different, the recognition of sex as
      a key variable in science and medicine is considered a revolution in some
      circles. Sex differences transcend reproductive functions, are evident in the
      structural and functional organization of the brain, and are reflected in group
      differences in cognitive abilities and behavior. Males and females have different
      neural organizational patterns for information processing and different
      strategies in problem solving. Research on sex differences not only provides
      descriptive data, but also allows us to elucidate mechanisms that underlie our
      behavior. In this review, sex differences in the central actions of nicotine (an
      addictive substance) and nitric oxide, and performance on active avoidance and
      place learning tasks are discussed as examples, and biobehavioral approaches
      relating to these topics are presented.

PMID- 11587777
TI  - Event-related markers of unconscious processes.
AB  - A series of studies is reviewed strongly suggesting that event-related potentials
      (ERPs) may provide markers for unconscious processes. In one study it was shown
      that, although smaller in amplitude by a least a factor of four, ERPs to
      subliminal stimuli have a similar component structure to ERPs to supraliminal
      stimuli. In another study, it was shown that an oddball P300 could be obtained
      for subliminal stimuli. In two additional studies, it was shown that aversive
      conditioning could be established unconsciously. The implications for our
      understanding of the role of unconscious processes in phobias and post-traumatic
      stress disorders are discussed, as well as more general implications for memory
      formation.

PMID- 11587778
TI  - Steady state visually evoked potential (SSVEP) topography in a graded working
      memory task.
AB  - The steady state visually evoked potential (SSVEP) elicited by a diffuse 13-Hz
      visual flicker was recorded from 64 scalp sites in 30 subjects performing a low
      and high demand version of an object working memory task. During the perceptual
      component of the task, the SSVEP amplitude was reduced at left and right parieto
      occipital sites. During the hold or memory component of the task, the SSVEP
      amplitude exhibited a load-dependent increase at frontal and occipito-parietal
      sites, while the SSVEP latency exhibited a load-dependent reduction at central
      and left frontal sites. We suggest that SSVEP amplitude changes index cortical
      information processing modes in that perceptual processes are associated with an
      SSVEP amplitude reduction, while holding information in active short-term or
      working memory is associated with an SSVEP amplitude increase. We also discuss
      changes in SSVEP amplitude and latency in terms of changes in the behavior of
      cortico-cortico and thalamo-cortico loops that utilize cortical layer I. Such
      cortico-cortico and thalamo-cortical loops are also proposed to constitute a
      neurophysiological mechanism for holding information in working memory.

PMID- 11587781
TI  - The intracellular function of extracellular signaling peptides.
AB  - A novel class of extracellular signaling peptides has been identified in Gram
      positive bacteria that are actively transported into the cell to interact with
      intracellular receptors. The defining members of this novel class of signaling
      peptides are the Phr peptides of Bacillus subtilis and the mating pheromones of
      Enterococcus faecalis. These peptides are small and unmodified, gene encoded, and
      secreted by the bacterium. Most of these peptides diffuse into the extracellular
      medium, and when their concentration is sufficiently high, they are then actively
      transported into the cell by an oligopeptide permease (Opp). Once inside the
      cell, these peptides interact with an array of intracellular receptors. In B.
      subtilis, the Phr peptides regulate development of environmentally resistant
      spores and genetically competent cells (i.e. the natural ability to take up
      exogenous DNA). In E. faecalis, the mating pheromones regulate cell-cell transfer
      of plasmids, many of which encode antibiotic resistance or virulence factors. At
      least one component of the signaling pathway for these peptides is conserved in
      many bacteria, Opp. Opp is a non-specific transporter that transports peptides
      for use as carbon and nitrogen sources. The possibility that other bacteria could
      possess similar intracellularly functioning signaling peptides is discussed.

PMID- 11587782
TI  - Peptide pheromone-induced transfer of plasmid pCF10 in Enterococcus faecalis:
      probing the genetic and molecular basis for specificity of the pheromone
      response.
AB  - The tetracycline resistance plasmid pCF10 represents a class of unique mobile
      genetic elements of the bacterial genus Enterococcus, whose conjugative transfer
      functions are inducible by peptide sex pheromones excreted by potential recipient
      cells. These plasmids play a significant role in the dissemination of virulence
      and antibiotic resistance genes among the enterococci, which have become major
      nosocomial pathogens. Pheromone response by plasmid-carrying donor cells involves
      specific import of the peptide signal molecule, and subsequent interaction of the
      signal with one or more intracellular regulatory gene products. The pheromones
      are chromosomally encoded hydrophobic octa- or hepta-peptides, and different
      families of homologous plasmids encode the ability to respond to each pheromone.
      Among the four pheromone-responsive plasmids that have been characterized in some
      detail, there is considerable conservation in the genes encoding pheromone
      sensing and regulatory functions, and the peptides themselves show considerable
      similarity. In spite of this, there is extremely high specificity of response to
      each peptide, with virtually no "cross-induction" of transfer of non-cognate
      pheromone plasmids by the pheromones. This communication reviews the evidence for
      this specificity and discusses current molecular and genetic approaches to
      defining the basis for specificity.

PMID- 11587783
TI  - Pentapeptide regulation of aspartyl-phosphate phosphatases.
AB  - Aspartyl-phosphate phosphatases are integral components of the phosphorelay
      signal transduction system for sporulation initiation in Bacillus subtilis. The
      Rap and Spo0E families of protein phosphatases specifically dephosphorylate the
      sporulation response regulators Spo0F and Spo0A, respectively. The phosphatases
      interpret regulatory signals antithetical to sporulation and the Rap phosphatases
      are subject to inactivation by specific pentapeptides generated from an inactive
      peptide precursor. Additional regulatory signals are brought about by the complex
      activation circuit that generates the Phr pentapeptide inhibitors of Rap
      phosphatases. Phr peptide's recognition of the Rap phosphatase targets is
      remarkably specific. Specificity is dictated by the amino acid sequence of the
      pentapeptide. The identification of tetratricopeptide repeats in the Rap proteins
      may explain the mechanism by which Phr peptides bind to and inhibit the activity
      of Rap phosphatases.

PMID- 11587784
TI  - A free terminal carboxylate group is required for PhrA pentapeptide inhibition of
      RapA phosphatase.
AB  - In the Bacillus subtilis phosphorelay signal transduction system for sporulation
      initiation, signals competing with the differentiation process are interpreted by
      aspartyl-phosphate phosphatases that specifically dephosphorylate the Spo0F or
      Spo0A response regulators. The RapA phosphatase is regulated by the PhrA
      pentapeptide that directly and specifically inhibits its activity. PhrA
      specificity for RapA inhibition is dependent upon the amino acid sequence of the
      peptide. Here we show that the pentapeptide affinity for the phosphatase requires
      a free carboxylate group at the C-terminal amino acid. A free C-terminal
      carboxylic acid PhrA pentapeptide inhibits RapA phosphatase activity at a 1:1
      ratio and it is approximately 200 fold more active than a C-terminal amide
      peptide. Therefore, coordination of the terminal carboxylate group appears to be
      critical for peptide binding to RapA.

PMID- 11587785
TI  - A peptide profile of the Bacillus subtilis genome.
AB  - Bacillus subtilis is known to produce an abundance of small polypeptides. Several
      of these have antimicrobial activity and others are pheromones or extracellular
      factors that affect internal signal transduction systems. The completion of the
      B. subtilis genomic nucleotide sequence has revealed 345 small polypeptide open
      reading frames (of 85 codons or less), 81% of which are of unknown function. A
      significant number of these reside in prophage genomes or phage-like elements
      where they can be organized into large operons. It is likely that many more exist
      in the genome of B. subtilis but are "hidden" entirely or partially within other
      reading frames, or possess non-conventional translation start signals and have
      escaped detection. The discovery of so many small polypeptide orfs (SPORFs) and
      the likelihood of many more pose a challenging problem for those undertaking the
      complete functional analysis of genes that constitute prokaryotic genomes. A
      survey of known and potential peptide-encoding reading frames is presented herein
      as an attempt to classify those that are found in the B. subtilis genome
      according to function inferred from homology searches and to conservation among
      products of other microbial genomes.

PMID- 11587786
TI  - Peptide pheromone-dependent regulation of antimicrobial peptide production in
      Gram-positive bacteria: a case of multicellular behavior.
AB  - Quorum sensing enables unicellular organisms to behave in a multicellular way by
      allowing population-wide synchronized adaptive responses that involve modulation
      of a wide range of physiological responses in a cell density-, cell proximity- or
      growth phase-dependent manner. Examples of processes modulated by quorum sensing
      are the development of genetic competence, conjugative plasmid transfer,
      sporulation and cell differentiation, biofilm formation, virulence response,
      production of antibiotics, antimicrobial peptides and toxins, and bioluminescence
      (for reviews see [38]). The cell-to-cell communication strategies involved in
      these processes are based on the utilization of small signal molecules produced
      and released into the environment by the microorganisms. These communication
      molecules are referred to as pheromones and act as chemical messengers that
      transmit information across space. The extracellular pheromones accumulate in the
      environment and trigger a response in the target cells when its concentration
      reaches a certain threshold value. Elucidation of the chemical nature of the
      pheromones modulating the processes mentioned above reveals that most of them are
      unmodified peptides, post-translationally modified peptides, N-acyl homoserine
      lactones, or butyrolactones. Lactone-based pheromones are the preferred
      communication signals in Gram-negative bacteria (for review see [47,48]), whereas
      peptide-based pheromones are the predominant extracellular signals among Gram
      positive bacteria (for review see [37,61]). However, lactone-based pheromones are
      utilized as signals that modulate differentiation and secondary metabolism
      production in Streptomyces (for review see [20]). This review focuses on the
      major advances and current views of the peptide-pheromone dependent regulatory
      circuits involved in production of antimicrobial peptides in Gram-positive
      bacteria.

PMID- 11587787
TI  - A two-component signal-transduction cascade in Carnobacterium piscicola LV17B:
      two signaling peptides and one sensor-transmitter.
AB  - In the lactic acid bacterium Carnobacterium piscicola LV17B a peptide-pheromone
      dependent quorum-sensing mode is involved in the regulation of bacteriocin
      production. Bacteriocin CB2 was identified as an environmental signal that
      induces bacteriocin production. Here, we demonstrate that a second 24 amino acid
      peptide (CS) also induces bacteriocin production. Transcription activation of
      several carnobacteriocin operons is triggered by CB2 or CS via a two-component
      signal transduction system composed of CbnK and CbnR.

PMID- 11587788
TI  - Staphylococcus aureus and Staphylococcus epidermidis peptide pheromones produced
      by the accessory gene regulator agr system.
AB  - The accessory gene regulator (agr) system of staphylococci regulates the
      expression of virulence factors in response to cell density. The extracellular
      signaling molecule encoded by this system is a thiolactone-containing pheromone
      peptide whose primary sequence varies among staphylococcal strains. A post
      translational modification of the peptide is believed to be carried out by an
      enzyme with a novel function, AgrB. Staphylococcal pheromones show cross
      inhibiting properties: Pheromones of self and pheromones of non-self induce and
      suppress the agr response, respectively, and have therefore been proposed as
      novel anti-staphylococcal drugs. As inhibition of agr leads to diminished
      expression of toxins, but to increased expression of colonization factors and
      biofilm formation, their therapeutic potential remains yet to be evaluated in
      depth.

PMID- 11587789
TI  - RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus
      pathogenesis: structure and function analysis.
AB  - Staphylococcus aureus are gram-positive bacteria that can cause serious diseases
      in humans and animals. S. aureus infections can be prevented by the heptapeptide
      RNAIII inhibiting peptide (RIP). RIP was originally isolated from culture
      supernatants of coagulase negative staphylococci presumed to be S. xylosus. The
      sequence of RIP was identified as YSPXTNF. Native RIP and its synthetic analogue
      YSPWTNF have been shown to be effective inhibitors of diseases caused by various
      strains of S. aureus, including, cellulitis, keratitis, septic arthritis,
      osteomylitis and mastitis. RIP is therefore considered to be a global inhibitor
      of S. aureus. We show here that: 1) the amide form of RIP (YSPWTNF-NH2) is highly
      stable and is therefore the one recommended for use. 2) RIP inhibits S. aureus
      pathogenesis by inhibiting the synthesis of both agr transcripts RNAII and
      RNAIII. 3) Although RIP inhibits agr, it also reduces bacterial adherence to
      mammalian cells and to plastic (tested on HEp2 cells and on polystyrene by
      fluorescence and atomic force microscopy), suggesting that RIP can be used safely
      as a therapeutic molecule. 4) RIP derivatives were designed and tested for their
      ability to inhibit RNAIII in vitro and cellulitis in vivo. Not all peptides that
      inhibited RNAIII also inhibited an infection in vivo, indicating that studies
      must be carried out in vivo before considering a peptide to be of therapeutic
      potential. 5) The RIP derivative containing Lysine and Isoleucine at positions 2
      and 4, respectively, inhibited S. aureus infections in vivo (tested on
      cellulitis), suggesting that both RIP YSPWTNF and its derivative YKPITNF are
      effective inhibitors of infections caused by S. aureus.

PMID- 11587790
TI  - RNAIII inhibiting peptide (RIP) inhibits agr-regulated toxin production.
AB  - Staphylococcal enterotoxins (SEs) are emetic toxins that cause food poisoning.
      SEs also function as powerful pyrogenic toxin superantigens that stimulate non
      specific T-cell proliferation. Together with the hemolysins, SEs have been
      largely implicated as virulence factors in multiple infection models. Recent
      biochemical and genetic analyses have demonstrated that production of some of
      these toxins is partially regulated by quorum sensing mechanisms where proteins
      and peptides activate the accessory gene regulator (agr). Because toxin
      production is central to bacterial pathogenesis, therapeutic strategies
      alternative to antibiotics, and based on rational interference of the quorum
      sensing systems involved, are currently being developed. This approach would lead
      to repression of toxin production and, thus, to disease prevention. Here we
      provide evidence to conclude that synthetic analogs of the RNAIII inhibiting
      peptide (RIP) and antibodies to its target molecule TRAP function in vitro as
      efficient suppressors of agr-regulated exotoxin production by Staphylococcus
      aureus.

PMID- 11587791
TI  - From "carpet" mechanism to de-novo designed diastereomeric cell-selective
      antimicrobial peptides.
AB  - Living organisms of all types produce a large repertoire of gene-encoded, net
      positively charged, antimicrobial peptides as part of their innate immunity to
      microbial invasion. Despite significant variations in composition, length and
      secondary structure most antimicrobial peptides are active in micromolar
      concentrations, suggesting a common general mechanism for their mode of action.
      Many antimicrobial peptides bind bacterial phospholipid membranes up to a
      threshold concentration, followed by membrane permeation/disintegration (the
      "carpet" mechanism). Recent data suggest that the details of the permeation
      pathways may vary for different peptides and are assigned to different modes of
      action. Accumulating data reveal that the molecular basis for cell selectivity is
      the ability of peptides to specifically bind the negatively charged bacterial
      membrane, as well as their oligomeric state in solution and in the membrane.
      Based on the "carpet" mechanism and the role of the peptide oligomeric state, a
      novel group of diastereomeric (containing D- and L-amino acids) antimicrobial
      peptides were developed. These peptides may serve as promising templates for the
      future designs of antimicrobial peptides.

PMID- 11587792
TI  - Processing site and gene structure for the murine antimicrobial peptide CRAMP.
AB  - Cathelicidins are a mammalian gene family notable for the presence of an
      antibiotic peptide encoded at the carboxy-terminal domain of the nascent pre-pro
      protein. Following proteolytic release, this peptide has direct antimicrobial
      activity. To understand the function and regulation of cathelicidin we
      investigated the peptide processing site and gene structure of the mouse
      cathelicidin CRAMP. Amino acid sequencing of the purified native 5 kDa peptide
      identified the functionally critical amino terminal sequence of mature CRAMP.
      Characterization of the CRAMP gene (Cnlp) showed homology in structure and
      sequence identity in several potential transcription factors binding sites found
      in the human cathelicidin LL-37. Overall, CRAMP shows striking similarities with
      LL-37, making it a useful model for study of human cathelicidin function and
      regulation.

PMID- 11587793
TI  - Staphylococcal resistance to antimicrobial peptides of mammalian and bacterial
      origin.
AB  - Antimicrobial host defense peptides, such as defensins, protegrins, and platelet
      microbicidal proteins are deployed by mammalian skin, epithelia, phagocytes, and
      platelets in response to Staphylococcus aureus infection. In addition,
      staphylococcal products with similar structures and activities, called
      bacteriocins, inhibit competing microorganisms. Staphylococci have developed
      resistance mechanisms, which are either highly specific for certain host defense
      peptides or bacteriocins or which broadly protect against a range of cationic
      antimicrobial peptides. Experimental infection models can be used to study the
      molecular mechanisms of antimicrobial peptides, the peptide resistance strategies
      of S. aureus, and the therapeutic potential of peptides in staphylococcal
      diseases.

PMID- 11587794
TI  - Short peptides conferring resistance to macrolide antibiotics.
AB  - Translation of specific short peptides can render the ribosome resistant to
      macrolide antibiotics such as erythromycin. Peptides act in cis upon the ribosome
      on which they have been translated. Amino acid sequence and size are critical for
      peptide activity. Pentapeptides with different consensus sequences confer
      resistance to structurally different macrolide antibiotics, suggesting direct
      interaction between the peptide and the drug on the ribosome. Translation of
      resistance peptides may result in expulsion of the macrolide antibiotics from the
      ribosome. The consensus sequence of peptides conferring erythromycin resistance
      is similar to the sequence of the leader peptide involved in translational
      attenuation of erythromycin resistance genes, indicating that a similar type of
      interaction between the nascent peptide and antibiotics can occur in both cases.

PMID- 11587795
TI  - The effect of charge increase on the specificity and activity of a short
      antimicrobial peptide.
AB  - By using short linear antimicrobial peptides as a model system, the effect of
      peptide charge on the specificity between Candida albicans (fungi) and Gram
      positive bacteria was investigated. In a present study, we added and/or deleted
      lysine residue(s) at the C-terminal and/or N-terminal end(s) of an antimicrobial
      peptide (KKVVFKVKFK-NH(2)) and synthesized the peptides that had similar alpha
      helical structures in a lipid membrane mimic condition. The increase of peptide
      charge improved antifungal activity without the change of antibacterial activity.
      Structure-activity relationship study about the peptides revealed that the net
      positive charge must play an important role in the specificity between C.
      albicans and Gram-positive bacteria and the increase of the net positive charge
      without the moderate change of secondary structure could improve activity for C.
      albicans rather than Gram-positive bacteria.

PMID- 11587797
TI  - Affinity driven molecular transfer from erythrocyte membrane to target cells.
AB  - A wide variety of antimicrobial peptides are known to bind to - and disrupt
      microbial plasma membranes. Recently, derivatives of the antimicrobial peptide
      dermaseptin S4 were shown to selectively disrupt the plasma membrane of the
      intracellular parasite Plasmodium falciparum without harming that of the
      mammalian host cell. The resulting antimalarial activity is allegedly exerted
      after the harmless peptide binding to the membrane of the host cell, followed by
      peptide translocation across a number of intracellular membrane systems and
      interaction with that of the intraerythrocyte parasite. In this study, we present
      evidence in support of the ability of a membrane-bound peptide, the dermaseptin
      S4 derivative K(4)-S4(1-13)a, to transfer from red blood cells (RBCs) to another
      distant membrane. Binding of K(4)-S4(1-13)a to the plasma membrane of RBCs was
      assessed in vitro and in vivo, and found to be rapid, spontaneous and receptor
      independent, as was the transfer of the RBC-bound peptide to the plasma membrane
      of microorganisms. The present study further provides a basis for the possible
      use of RBCs as a transport vehicle to deliver drugs to distant targets. This drug
      delivery system involves the transient "loading" of RBCs with a lipophilic "hook"
      peptide. Such a peptide has enough affinity for the RBC's plasma membrane to bind
      to the membrane, but given the opportunity, the peptide will exit its position
      and transfer to another (target) cell for which it has a greater affinity. The
      efficacy of such an affinity driven transfer system was demonstrated
      experimentally by the transfer of K(4)-S4(1-13)a from pre-loaded RBCs to
      bacteria, yeast and protozoan target cells.

PMID- 11587796
TI  - N-terminal modifications of Polymyxin B nonapeptide and their effect on
      antibacterial activity.
AB  - Polymyxin B (PMB) is a potent antibacterial lipopeptide composed of a positively
      charged cyclic peptide ring and a fatty acid containing tail. Polymyxin B
      nonapeptide (PMBN), the deacylated amino derivative of polymyxin B, is much less
      bactericidal but able to permeabilize the outer membrane of Gram-negative
      bacteria and to neutralize the toxic effects of lipopolysaccharide (LPS). In this
      study, we synthesized and evaluated the antibacterial and LPS neutralizing
      activities of four PMBN analogs modified at their N-terminal. Our results suggest
      that oligoalanyl substitutions of PMBN do not effect most of PMBN activities.
      However, a hydrophobic aromatic substitution generated a PMB-like molecule with
      high antibacterial activity and significant reduced toxicity.

PMID- 11587799
TI  - Factors influencing vaccine uptake in Germany.
AB  - While vaccines have virtually eliminated many infectious diseases in Germany,
      vaccination coverage in children, adolescents and adults is still unsatisfying.
      This situation is mainly due to inadequate remuneration of vaccination services,
      structural deficits in the health care system and a lack of motivation. Political
      support and leadership would most likely be able to change this situation.

PMID- 11587800
TI  - Analysis of factors influencing vaccine uptake: perspectives from Belgium.
AB  - METHODS AND OBJECTIVES: To estimate the infant vaccination coverage in Belgium, a
      random cluster sample according to the expanded program on immunization (EPI)
      cluster sampling technique was performed in 1999 in the Flemish (Flanders) and
      French (Wallonia) speaking community of Belgium. The objective was to document
      the infant vaccination coverage retrospectively in 18-24-month-old children. In
      addition, the study offered the opportunity to assess some factors influencing
      vaccine uptake in infants. RESULTS: In the Flemish community infant vaccination
      coverage could not be associated with any of the socio-demographic factors, with
      two exceptions: the province (county) and the hepatitis B (HepB) vaccination. The
      main reason for not complying with the vaccination schedule was mainly
      carelessness on either parent's or physician's side. In the French speaking
      community parents feel mostly themselves responsible for the non-vaccination or
      incomplete vaccination of their child, except for pertussis. For all vaccines,
      the attitude of the physician is mentioned as being very influential in the
      decision to vaccinate a child. Most of the socio-demographic factors showed no
      association with the infant vaccination coverage. CONCLUSION: The surveys in
      Flanders and Wallonia stress the importance of having information made available,
      and underline the role parents as well as physicians (and nurses) play in the
      infant immunization coverage.

PMID- 11587801
TI  - Factors influencing vaccine uptake in Italy.
AB  - In Italy, vaccination of children is regulated by a dual system, that is a
      certain number of compulsory immunisations, and a number of other facultative
      vaccinations. This has resulted in a different coverage against infections under
      the two regimens. While the percentage of immunised children against polio,
      diphtheria, tetanus and hepatitis B is around 95%, until recently the average
      coverage with facultative vaccinations was no >50%. Coverage against pertussis
      has dramatically increased in recent times thanks to the advent of acellular and
      combined vaccines. Regional programmes that aim to increase coverage against
      measles, mumps and rubella are presently underway. In order to verify the
      attitude of mothers towards vaccination, a questionnaire-based study was proposed
      to women taking their children to vaccination services for mandatory
      immunisation. The preliminary results on 300 questionnaires show a generally
      favourable attitude towards vaccines of 80% of mothers. Only 7% of them would not
      immunise at all their children if vaccinations were not mandatory. Measles and
      mumps vaccines are considered important by 92% of mothers. However, a high number
      of both parents and paediatricians still give disproportionate importance to mild
      intercurrent diseases as a reason to differ immunisation. In the middle-long
      term, it is likely that Italy will shift to a system of recommended immunisations
      without compulsion. Before this happens, wide and in-depth campaigns on the
      benefits of vaccination need to be planned and implemented by central and local
      health authorities, in order to avoid the risk of a dramatic drop of coverage.

PMID- 11587802
TI  - Analysis of factors influencing vaccine uptake: perspective from Spain.
AB  - Although each of the 17 Autonomous Regions in Spain has their own vaccination
      policies, factors influencing vaccine uptake do not differ considerably among
      them. Knowledge of vaccine preventable diseases, awareness that the diseases
      prevented by vaccinations are serious or very serious, awareness that
      vaccinations are not generally associated with serious adverse events, cost-free
      status and satisfaction with our computerised immunization registry, are the
      elements which influence vaccine uptake in our country.

PMID- 11587803
TI  - Lessons learned concerning vaccine safety.
AB  - The safety of vaccines is an issue that has been with us ever since Jenner, and
      it will not go away. The author argues that despite what may seem a waste of
      energy, most proposed relationships between vaccines and reactions must be
      thoroughly investigated, as some have been proved correct. Investigations that
      show the putative relationship to be incorrect serve as examples of scientific
      rigor, which are valuable for the public. The author draws eight lessons for the
      future from our recent experiences.

PMID- 11587804
TI  - Predictive value of pre-clinical work for vaccine safety assessment.

PMID- 11587805
TI  - Alternative vaccine strategies to prevent serogroup B meningococcal diseases.

PMID- 11587806
TI  - Immunopathogenesis of vaccine-enhanced RSV disease.
AB  - Inducing a strong immune response is an essential aim of vaccination. Although
      immune responses to virus infections are usually protective, they can also be
      harmful. The best-documented examples of an immune response increasing disease
      severity are with dengue, measles and respiratory syncytial virus infections. In
      the 1960s, administration of formalin-inactivated, tissue culture grown RSV (FI
      RSV) was found to induce strong ELISA binding but poor virus-neutralising
      antibody. Infants given this 'lot 100' vaccine appeared to exhibit an increased
      rate of RSV infection during subsequent natural RSV outbreaks. Although it has
      not been possible to exactly delineate the cause of disease enhancement in man,
      animal models strongly suggest that it was due to strong (and perhaps unbalanced)
      T cell priming rather than infection-enhancing or sensitising antibody. In animal
      models, enhanced disease can result from over-exuberant T cell priming which
      recruits an abundant inflammatory infiltrate in the lung (the nature of which
      depends on the patterns of cytokines and chemokines produced). Formalin-treated
      RSV vaccination has been linked specifically to the induction of Th2 cells, which
      make IL-4 and IL-5 and induce a strong pulmonary eosinophilic response. The
      vaccine dosing regime and the interval between vaccination and challenge can be
      critical to the induction of protection or pathology. Defining the correlates of
      protection and disease enhancement in man is critical to the rational development
      of effective and protective vaccines against RSV.

PMID- 11587807
TI  - Respiratory syncytial virus vaccine development.
AB  - Development of an RSV vaccine for infants has been hindered by the lack of an
      ideal animal model that exhibits disease, and the challenge of effectively
      immunizing very young infants who are immunologically immature. Nevertheless,
      significant progress has been made recently in developing live attenuated viruses
      and protein subunit vaccine candidates. Numerous vaccine candidates are currently
      in early clinical trials. This paper reviews the significant obstacles to
      development of RSV vaccines, and the progress made to date.

PMID- 11587808
TI  - What are the limits of adjuvanticity?
AB  - Vaccines developed traditionally following empirical approaches have often
      limited problems of immunogenicity, probably due to the low level of purity of
      the active component(s) they contain. The application of new technologies to
      vaccine development is leading to the production of purer (e.g. recombinant)
      antigens which, however, tend to have a poorer immunogenicity as compared to
      vaccines of the previous generation. The search for new vaccine adjuvants
      involves issues related to their potential limits. Since the introduction of
      aluminium salts as vaccine adjuvants more than 70 years ago, only one adjuvant
      has been licensed for human use. The development of some of these new vaccine
      adjuvants has been hampered by their inacceptable reactogenicity. In addition,
      some adjuvants work strongly with some antigens but not with others, thus,
      limiting their potentially widespread use. The need to deliver vaccines via
      alternative routes of administration (e.g. the mucosal routes) in order to
      enhance their efficacy and compliance has set new requirements in basic and
      applied research to evaluate their efficacy and safety. Cholera toxin (CT) and
      labile enterotoxin (LT) mutants given along with intranasal or oral vaccines are
      strong candidates as mucosal adjuvants. Their potential reactogenicity is still
      matter of discussions, although available data support the notion that the
      effects due to their binding to the cells and those due to the enzymatic activity
      can be kept separated. Finally, adjuvanticity is more often evaluated in terms of
      antigen-specific antibody titers induced after parenteral immunization. It is
      known that, in many instances, antigen-specific antibody titers do not correlate
      with protection. In addition, very little is known on parameters of cell-mediated
      immunity which could be considered as surrogates of protection. Tailoring of new
      adjuvants for the development of vaccines with improved immunogenicity/efficacy
      and reduced reactogenicity will represent one of the major challenges of the
      ongoing vaccine-oriented research.

PMID- 11587809
TI  - Pre-clinical and clinical investigation of the safety of a novel adjuvant for
      intranasal immunization.
AB  - Nasalflu Berna is a trivalent influenza virus vaccine for active immunization
      against influenza by the nasal route. It consists of influenza virosomes which
      are formulated from inactivated influenza strains and heat-labile toxin from
      aseptic Escherichia coli bacteria strain, as an adjuvant (HLT). The results of
      preclinical studies in ferrets, baboons, minipigs, mice and rabbits are presented
      here, and issues concerning route of administration, mechanism of action
      (preventing the disease and halting further spread of the disease), and the
      specific safety issues of the adjuvant itself (possible neurological activity of
      HLT) are examined. No clinical signs were detected in the animals, and
      hematological values were in the normal range. In particular, there was no
      evidence of any systemic adverse reaction, including sensitization to the test
      substances, and no evidence of possible neurological activity of the HLT. Further
      clinical studies in humans conducted over five influenza seasons using this
      virosome-formulated intranasal vaccine, elicited high levels of influenza
      specific hemagglutination inhibition IgG antibody titers to the strains
      incorporated in the administered vaccine. In addition, IgA antibodies were also
      elicited in the nasal mucosa, and in the saliva. In addition to the systemic IgG
      antibody titers, the nasal mucosal IgA antibody response may provide additional
      local protection by the inhibition of viral replication and further spread in the
      respiratory tract. Nasalflu was well tolerated by most of the vaccinated
      subjects, both in terms of nasal symptoms and possible vaccination-mediated
      systemic symptoms. Both local and systemic symptoms were primarily mild, with
      only an occasional subject reporting moderate intensity. Out of four serious
      adverse events seen during the clinical development, only one was thought to be
      remotely related to the test vaccine.Nasalflu, developed by the Swiss Serum and
      Vaccine Institute, is a novel, highly immunogenic and safe influenza subunit
      vaccine which is easily administered as a nasal spray. This new route of
      administration is likely to increase compliance to vaccination, and could become
      an important tool to promote vaccination in population groups which show high
      resistance to vaccination.

PMID- 11587811
TI  - Detection of adverse events: what are the current sensitivity limits during
      clinical development?

PMID- 11587812
TI  - Statistical assessment of the association between vaccination and rare adverse
      events post-licensure.
AB  - Once a new vaccine has been licensed and is in widespread use, it is important to
      be able to detect and investigate adverse events which may be associated with the
      vaccine. This is particularly important for rare events which may have been
      missed in pre-licensure studies. Recent studies investigating adverse events
      following vaccination have used either a population or a sample of the population
      (cohort studies), cases matched to controls (case-control studies), or just
      information on the cases themselves (self-controlled case-series studies). In
      this paper, the three methods are reviewed and compared and examples are given of
      recent applications. The effects of potential sources of bias are demonstrated
      using a data set on MMR vaccine and convulsions.

PMID- 11587813
TI  - Primum non nocere in vaccinology.

PMID- 11587814
TI  - Planning, registration, and implementation of an immunisation campaign against
      meningococcal serogroup C disease in the UK: a success story.
AB  - The introduction of meningococcal C conjugate (MCC) vaccine in the UK in November
      1999 as a routine 3 dose infant immunisation course, with a single catch-up dose
      for all children aged between 12 months and 17 years, was the result of an
      intensive 5 year collaborative research programme funded by the Department of
      Health for England and involving public bodies, academia and vaccine
      manufacturers. The research programme established the safety and immunogenicity
      of MCC vaccines in infants, toddlers, pre-school and school-aged children. The
      nature and frequency of common adverse events in school-aged children was similar
      to that after a booster dose of diphtheria and tetanus vaccine given to the same
      age groups. The recommendation that a single dose was adequate for children aged
      12 months and above was based on antibody levels measured by serum bactericidal
      assay and evidence of induction of immunological memory as shown by maturation of
      antibody avidity. Licensure by the Medicines Control Agency was based on
      serological criteria alone without direct evidence of efficacy and has set a
      precedent for other meningococcal conjugate polysaccharide vaccines. Vaccine
      coverage of around 85% was achieved in the targeted age groups and has resulted
      in a drop in the incidence of serogroup C disease in these groups of over 80%
      within 18 months of the start of the vaccination programme. Early post-licensure
      efficacy estimates for toddlers and teenagers (88 and 96%, respectively, in the
      first 16 months after vaccination) validate the serological criteria used for
      licensure. Surveillance of the prevalent serogroups and serosubtypes among
      invasive case isolates has shown no evidence of any capsular switching to
      serogroup B during the first 18 months of the MCC vaccination programme.

PMID- 11587815
TI  - Regulating vaccines involving new technologies to ensure safety and timely
      licensure--the challenge.

PMID- 11587816
TI  - Developing vaccines involving new technologies to ensure safety and timely
      licensure. The industry perspective.

PMID- 11587817
TI  - Maternal immunization: the influence of liability issues on vaccine development.

PMID- 11587819
TI  - Perception of risk of vaccine adverse events: a historical perspective.
AB  - The psychology of risk perception puts the emotive evaluation of the risks
      associated with vaccination incorrectly into a high risk category. This causes a
      wariness of taking vaccines that has its roots in the deep history of people.
      Humans do not seek to disturb the status quo by which they live. So the
      introduction of a vaccinal material into a healthy baby requires courage and an
      educated anticipation that some important benefit will accrue to this act at some
      future date. This situation encourages the emergence of a resistance to vaccines
      and the establishment of propagandists and movements to promote such ideas. The
      origin and development of such movements and the arguments which they prefer are
      the subject of this paper. These are based on religion in the first instance and
      then they widen to include the practical and technical problems which the early
      vaccinators experienced. The making of vaccination against smallpox compulsory at
      law in the UK in (effectively) 1867, inspired a most active and able opposition
      to vaccination. The concerns which such movements raise and ways in which they
      may be addressed are dealt with in the final sections.

PMID- 11587820
TI  - Benefit and risk of vaccination as seen by the general public and the media.

PMID- 11587822
TI  - Rise in popularity of complementary and alternative medicine: reasons and
      consequences for vaccination.
AB  - Complementary and alternative medicine (CAM) has become a popular form of
      healthcare and the predictions are that, it will increase further. The reasons
      for this level of popularity are highly diverse, and much of the motivation to
      turn to CAM pertains to a deeply felt criticism of mainstream medicine - many
      people (are led to) believe that conventional interventions, including
      immunisation, are associated with the potential to do more harm than good. Thus,
      it is hardly surprising that CAM also lends support to the "anti-vaccination
      movement". In particular, sections of the chiropractors, the (non-medically
      trained) homoeopaths and naturopaths tend to advise their clients against
      immunisation. The reasons for this attitude are complex and lie, at least in part
      in the early philosophies which form the basis of these professions. The negative
      attitude of some providers of CAM towards immunisation constitutes an important
      example of indirect risks associated with this form of healthcare. The best way
      forward, it seems, would be a campaign to clarify the risk-benefit profile of
      immunisations for both users and providers of CAM.

PMID- 11587824
TI  - How to improve communication on vaccine safety at international level?

PMID- 11587825
TI  - How to improve communication on vaccine issues at the national level? INFOVAC
      PED: an example from Switzerland.
AB  - For physicians in private practice, rapid access to relevant and up-to-date
      objective information is required to better meet their clients' concerns on
      vaccine-related issues. To meet this need, INFOVAC-PED, an academic network of on
      call pediatric infectious diseases experts who can be reached free of charge at a
      central e-mail address, now answers Swiss physicians' questions within 24-48h.
      INFOVAC-PED also distributes monthly bulletins including news from the Federal
      Office of Public Health, vaccine producers, literature survey, and answers to
      most frequently asked questions. The rapid success of this novel initiative
      underlines the need to better support front line physicians.

PMID- 11587826
TI  - The future of vaccines: an industrial perspective.

PMID- 11587827
TI  - Business perspectives of a European vaccine manufacturer.

PMID- 11587828
TI  - Isolation of Neospora caninum from the brain of a naturally infected dog, and
      production of encysted bradyzoites in gerbils.
AB  - Neospora caninum was isolated from the brain of an adult dog in Brazil. Cerebral
      tissue from the dog was inoculated into Mongolian gerbils. Gerbils were
      euthanized 3-4 months later and bradyzoite-containing tissue cysts were observed
      in their brains. N. caninum (designated NC-Bahia) was isolated in cell culture
      after inoculation with tissue cysts from the gerbils. The identity of the
      parasite was confirmed by immunohistochemical examination and polymerase chain
      reaction (PCR). Gerbils may be a useful alternative to immunosuppressed mice for
      isolation of N. caninum and for production of encysted bradyzoites.

PMID- 11587829
TI  - Detection of Babesia equi (Laveran, 1901) by nested polymerase chain reaction.
AB  - We describe a nested polymerase chain reaction (PCR) for the detection of Babesia
      equi in equine infected erythrocytes using oligonucleotides designed on the
      published sequence of a B. equi merozoite antigen gene (ema-1). A 102bp DNA
      fragment is specifically amplified from B. equi but not from Babesia caballi,
      Babesia bovis or Babesia bigemina DNA. In a mock infection we were able to detect
      down to six infected cells in 10(8) equine erythrocytes or to detect the parasite
      in blood with an equivalent parasitemia of 0.000006%. Furthermore, gene
      polymorphism was found by performing a PCR-RFLP (PCR combined with restriction
      fragment length polymorphism) on both the 102bp and the entire ema-1 gene DNA
      amplified from two B. equi isolates, Florida (USA) and Pelotas (Southern Brazil)
      isolates. The polymorphism was confirmed by sequencing the entire ema-1 gene from
      the B. equi isolate Pelotas. Our results demonstrate that the ema-1 based nested
      PCR is a valuable technique for routine detection of B. equi in chronically
      infected horses. It may be used for epidemiological and phylogenetic studies of
      the parasite as well as monitoring B. equi infected horses in chemotherapeutic
      trials.

PMID- 11587830
TI  - Meningeal leishmaniosis induced by Leishmania infantum in naturally infected
      dogs.
AB  - We report two cases of meningitis caused by Leishmania infantum in naturally
      infected dogs. In both of these dogs the typical phenotypic features of
      granulomatous meningitis were observed with important lympho-plasma-cellular
      infiltrates and the presence of large numbers of parasites inside and outside
      macrophages. The immunological study of the cerebrospinal fluid of both animals
      showed that a large number of protein bands were recognized by those fluids and
      that they were similar to the ones recognized by the sera from the same animals.
      To our knowledge, this is the first description of meningitis associated to
      leishmaniosis.

PMID- 11587831
TI  - Gastrointestinal nematodes of cattle in the northeastern US: results of a
      producer survey.
AB  - A questionnaire covering management practices and producer perception of the
      effects of gastrointestinal nematode infections was sent to dairy and beef
      producers in the northeastern US. The mailing list was derived from membership in
      grazing groups and attendance at grazing events. A final total of 474 responses
      were suitable for analyses. These responses covered 14 states, but for the
      purpose of analysis were broken into five groups: New England (NE), Vermont (VT),
      New York (NY), Pennsylvania (PA), and south and west (S and W) of Pennsylvania.
      Two-thirds of the responses were from dairy producers. The average number of
      animals for the farms was 50 cows, 27 heifers, and 20 calves. The average acreage
      used for grazing was 70 acres, and about two-thirds of the responses used
      rotational grazing for at least the cows. About one-half of the rotational
      grazers had been practicing rotational grazing for more than 5 years. Most
      rotational programs for cows involved a daily rotation, but the rotational
      interval for other age groups was longer. There was a difference of about 2
      months (5.25-7.27) in the length of the grazing season as one moved from New
      England to south and west of Pennsylvania. Parasite control practices varied
      greatly by location and animal class. Most producers used anthelmintics one to
      two times per year, but 10-30% of responses said they did not deworm their
      cattle. The most common time to deworm was in the spring, and the second most
      common time was the fall. Between 10 and 20% of respondents reported deworming as
      a response to decreased productivity or body condition. The use of anthelmintics
      increased as the location moved from New England to south and west of
      Pennsylvania. Producer perception of parasite effects was closely related to
      their anthelmintic use, and also increased as the location moved to the south,
      and is most likely the result of the increased length of the grazing season. Of
      producers who ascribed estimated a cost of the parasite, the majority estimated
      this cost to be between US$ 5 and 20 per animal per year.

PMID- 11587832
TI  - Epidemiological aspects of bovine parasitic otitis caused by Rhabditis spp.
      and/or Raillietia spp. in the state of Minas Gerais, Brazil.
AB  - The occurrence of bovine external otitis in tropical regions is predominantly
      assigned to parasitic infections by rhabditiform nematodes and infestations by
      mites of the genus Raillietia. This research had the purpose of investigating the
      prevalence of parasitic otitis in the dry and rainy seasons of Minas Gerais and
      correlating it with variables age, breed and the presence of horns. The secretion
      or cerumen of 981 cattle was collected with sterile swabs, placed in test tubes
      and exposed to sunlight for the identification of clinical infections caused by
      rhabditiform nematodes. The ear canals of 109 animals were flushed to study the
      occurrence of mites of the genus Raillietia. Clinical otitis caused by
      rhabditiform nematodes was observed only in animals of the Gyr breed, affecting
      169 (60.1%) of the total (278) of these cattle. The prevalence of otitis in this
      breed was significantly higher for mature adult cows (P<0.001) and in cows with
      horns (P<0.001). In a total of nine animals suspected of raillietiosis, the
      examinations revealed the presence of Raillietia spp. in two Dutch cows. These
      results demonstrate that treatment must be focused on adult Gyr cattle with
      horns. This and future studies with an emphasis on epidemiological aspects may
      contribute to development of alternative approaches to reduce disease.

PMID- 11587833
TI  - Oestrus ovis (Diptera: Oestridae): sheep humoral immune response to purified
      excreted/secreted salivary gland 28 kDa antigen complex from second and third
      instar larvae.
AB  - The potential of Oestrus ovis larvae excretory-secretory products (ESP), crude
      extract, salivary gland contents (SGc) and digestive tube contents (DTc) proteins
      from O. ovis larvae as antigens in serological assay were analyzed and compared.
      This study demonstrated that excretory-secretory proteins were produced mainly by
      digestive tube and salivary gland. The main antigenic component of ESP was a
      28kDa protein complex (pc28) synthesized by the salivary gland ring. After
      purification, its diagnostic value was estimated by an ELISA using sheep sera
      sampled in summer (n=30) and winter (n=69) in order to investigate the relative
      importance of wintering hypobiotic first instar larvae on animal responsiveness.
      ELISA test based on pc28 antigen was compared to a reference ELISA test based on
      second instar larvae crude extract. After comparison it appeared that the pc28
      test was much more specific (87%) and more sensitive (90%) in summer. Anti-pc28
      antibody titers were significantly higher in summer than in winter demonstrating
      the impact of summer developing larvae on the humoral systemic immune response.
      This data was correlated to the maturation of larvae in summer as the number of
      larvae at necropsy was significantly higher in winter, when the larval population
      is only represented by first instar larvae, than in summer. No correlation was
      observed between the mean antibody titers and the number of larvae.

PMID- 11587834
TI  - Toxicity of cypermethrin and diazinon to Haematobia irritans (Diptera: Muscidae)
      in its American southern range.
AB  - Synthetic pyrethroids are considered currently less effective than
      organophosphate insecticides for controlling Haematobia irritans on cattle in its
      American southern range. To test the validity of this hypothesis, horn fly
      populations from 95 cattle herds in central-northern Argentina and southern
      Brazil were evaluated to determine 50% lethal concentrations (LC(50)) to
      cypermethrin and diazinon, respectively. Horn flies were exposed to filter papers
      and glass vials treated with cypermethrin and diazinon, respectively, and LC(50)
      values were determined using probit analysis. Two and 78 fly populations showed
      LC(50) values indicating susceptibility and resistance to cypermethrin,
      respectively, in comparison to historical LC(50) values obtained when the horn
      fly populations were susceptible to cypermethrin. Five fly populations had an
      undetermined resistance status to cypermethrin. The diazinon tests showed no
      obvious indications of H. irritans resistance. Thirty nine percent of farmers
      still rely on pyrethroids to control horn fly populations on cattle which
      represents a decreasing proportion from a few years ago when horn fly control was
      carried out using pyrethroids almost exclusively. Organophosphates could provide
      control for horn flies resistant to pyrethroids; however, the reliance on
      chemicals alone to control H. irritans is not considered a proper approach for
      the future.

PMID- 11587835
TI  - Cyathostome fecal egg count trends in horses treated with moxidectin, ivermectin
      or fenbendazole.
AB  - Commercial preparations of fenbendazole (Safe-Guard, Intervet), ivermectin
      (Eqvalan, Merial) or moxidectin (Quest, Fort Dodge) were administered once to
      horses scheduled for routine parasiticide treatment. In total, 93 horses from six
      cooperating farms were used in the study. Computer generated, random allocation
      of horses to treatment group was conducted at each farm. Fecal egg counts were
      determined for all horses on trial days 0, 56, 84 and 112, with corresponding
      calendar dates that were unique to each farm. Only strongyle egg counts from
      animals which were positive at day 0 were used for analysis of variance and
      comparisons. Counts for the three treatment groups were similar at day 0,
      moxidectin<ivermectin<fenbendazole for days 56 and 84, and
      moxidectin<ivermectin=fenbendazole on day 112 (P<0.05). Reductions of geometric
      mean egg counts from day 0 levels were 99.1, 97.6 and 94.9% for moxidectin, 16.4,
      -27.0 and -32.0% for fenbendazole and 85.9, 24.2 and -8.1% for ivermectin on
      trial days 56, 84 and 112, respectively. Adverse reactions to treatment were not
      observed for any of the parasiticides.

PMID- 11587837
TI  - Evaluation of beta-cyclodextrin against natural infections of cryptosporidiosis
      in calves.
AB  - The effectiveness of beta-cyclodextrin, excipient used in pharmaceutical
      industry, in the treatment of natural infection by Cryptosporidium parvum in
      suckling calves, was evaluated. Administration of the drug at a dose of 500 mg/kg
      body weight for 3 consecutive days from birth (prophylactically) or following
      confirmation of the infection (therapeutically) decreased the severity of
      diarrhoea and shortened the duration of oocyst shedding.

PMID- 11587838
TI  - Impact of field vaccination with a Theileria annulata schizont cell culture
      vaccine on the epidemiology of tropical theileriosis.
AB  - Tropical theileriosis, caused by Theileria annulata, is an important tick-borne
      disease of cattle. A cell culture attenuated vaccine has been developed in our
      laboratory by long-term in vitro propagation of the schizont stage of the
      parasite. A longitudinal study was conducted at selected farms housing
      indigenous, cross-bred and exotic animals to investigate the effect of
      vaccination on the epidemiology of the disease. A total of 120 animals in 4 age
      groups were vaccinated with the vaccine before the onset of disease season. An
      equal number of age-matched animals were kept as controls at the same sites.
      Animals were monitored for 14 months at monthly intervals. The 97.5% vaccinated
      animals showed a rise in antibody titres 1 month post-vaccination, as determined
      by single dilution ELISA. The 78.3% of non-vaccinated animals became sero
      positive over the period of observation. Mean antibody titres were significantly
      higher in vaccinated than non-vaccinated animals. Cross-bred animals showed
      higher antibody titres followed by exotic and indigenous animals in both the
      vaccinated and non-vaccinated groups. However, the antibody titres in animals of
      different ages were similar. The 36.7% vaccinated and 64.2% non-vaccinated
      animals became carriers (<0.5% piroplasms in erythrocytes) during the observation
      period. Clinical cases of theileriosis were recorded only in the non-vaccinated
      group suggesting that vaccinated animals were sufficiently immune to withstand
      field tick challenge for at least 14 months.

PMID- 11587839
TI  - Prevalence and incidence of trypanosomosis in horses and donkeys in the Gambia.
AB  - In a study of the prevalence and incidence of trypanosomosis in horses and
      donkeys in two regions of the Gambia, surveys were carried out at Niamina east
      and Bansang south with a high and low to moderate tsetse challenge, respectively.
      Eleven horses and 67 donkeys were sampled monthly from August 1997 to September
      1998. Blood samples were examined for trypanosomes using the buffy-coat (BC)
      method and polymerase chain reaction (PCR). Three primer sets were used, specific
      for either Trypanosoma vivax (TVW), Trypanosoma congolense (GOL) or Trypanosoma
      brucei (ORPHON5J). The BC results showed that the prevalence (August 1997) and
      the average monthly incidence (September 1997-1998) of trypanosome infections in
      horses (45.5 and 16%, respectively) were significantly higher than in donkeys
      (6.2 and 9%, respectively). Using PCR, the number of detected cases was seven
      times higher than using the BC. T. congolense was the most frequently observed
      species, followed by T. vivax and T. brucei. This study confirms earlier
      observations by other authors that donkeys, which are exposed to a similar tsetse
      challenge as horses, are significantly less infected with trypanosomes than the
      latter.

PMID- 11587840
TI  - Ocular onchocercosis in dogs: aberrant infection in an accidental host or lupi
      onchocercosis?
AB  - Four adult dogs that had spent their entire life in Hungary, were found to be
      infected with filaroid nematodes of the genus Onchocerca. The morphology and
      location of the parasites as well as pathological lesions were similar to those
      described earlier in the one Hungarian and five US dogs. Only moderate
      morphological differences were noted between the adults of Onchocerca sp.
      infecting dogs and O. volvulus of man or O. lienalis of cattle. Nevertheless, the
      morphology of microfilariae of Onchocerca from dogs is unique within the genus.
      Their length was less than half the length of microfilariae of other Onchocerca
      spp. known so far. In addition to size differences, several characteristic
      morphological features were observed. The unsuccessful attempt to infect dogs
      with O. lienalis, the absence of O. volvulus and O. lienalis in endemic regions
      of canine onchocercosis, the different size, morphology, and location of the
      adults in dogs and cattle, the exceptionally small size and unique morphology of
      microfilariae of Onchocerca of canids indicate that a distinct species might be
      responsible for canine onchocercosis. Since the larval concentration in the skin
      was high (50-3600 microfilariae g(-1)) in all affected dogs, the diagnosis prior
      to surgical removal of worm nodules can be based on the examination of a small
      skin snip collected from the head or abdominal region. Infections in dogs may
      provide a model to study human onchocercosis, therefore, further studies are
      encouraged on the feasibility of experimental infection of dogs with this
      Onchocerca species.

PMID- 11587841
TI  - Comparison of nematode infections of the gastrointestinal tract in Angora and
      dairy goats in a rangeland environment: relations with the feeding behaviour.
AB  - A study was conducted in order to examine the possible influence of feeding
      behaviour on differences in the diversity and the intensity of nematode
      infections of the gastrointestinal tract between two breeds of goats placed in
      the same rangeland environment. Within the same flock bred on rangeland
      conditions, 10 Saanen dairy goats and 14 Angora goats were surveyed for 5 months
      (from May to September) and parasitological and behavioural parameters were
      measured. The level of nematode infection was estimated by monthly measurements
      of faecal egg counts whereas the feeding behaviour was assessed every fortnight.
      During the whole survey, nematode egg excretion was repeatedly higher in the
      Angora goats compared to the Saanen ones and significant differences were
      observed in May and September. This difference in egg excretion was related to
      major difference in feeding behaviour between the two breeds. In contrast with
      the Saanen does, Angora goats did not show any browsing and resting activities at
      any date of observation. Hence, Angora goats can be considered mainly as grazers
      whereas Saanen goats exhibit feeding activities close to browsers. The relative
      influence of feeding behaviour and host immune response on the susceptibility to
      gastrointestinal nematode infection in goats is discussed.

PMID- 11587842
TI  - Inactivation of eggs and larvae of the cattle nematodes Ostertagia ostertagi and
      Cooperia oncophora after passage in pigs.
AB  - The study investigated the effect of gastrointestinal passage in pigs on free
      living stages of bovine nematodes. Two Landrace x Yorkshire pigs, A and B, were
      fed fresh eggs of Ostertagia ostertagi and Cooperia oncophora while two other
      pigs, C and D, were fed third stage larvae (L3) of the same parasites. Faeces
      from the pigs were collected for 48 h after ingestion. In pigs A and B, 15 and
      66% of the eggs were recovered after passage, respectively. However, only 0.003
      and 0.002% of the ingested eggs developed into third stage larvae (L3) after
      subsequent culturing. In pigs C and D, 0.01 and 0.02% of the L3 survived the
      passage of the gastrointestinal tract. Fresh O. ostertagi and C. oncophora eggs
      were cultured in parasite free porcine and bovine faeces. Only 0.05% L3 developed
      in porcine faeces, whereas 21% of the eggs developed into L3 in the bovine
      culture. Our results demonstrate an extremely poor rate of development and
      survival of both bovine nematode eggs and infective larvae after passage in pigs.
      It may imply that pigs can play an important role in reducing transmission of
      cattle nematodes if the two species are grazed together or alternately.

PMID- 11587843
TI  - Ecological influences on transmission rates of Ascaris suum to pigs on pastures.
AB  - A study was conducted to determine the distribution and transmission rate of
      Ascaris suum eggs and Oesophagostomum dentatum larvae in a pasture/pig house
      facility, which during the preceding summer was contaminated with helminth eggs
      by infected pigs. In May, four groups of 10 helminth naive tracer pigs were
      exposed to fenced sections of the facility for 7 days and necropsied for parasite
      recovery 9-10 days later (trial 1). The highest rate of A. suum transmission (201
      eggs per day) occurred in the pig house (A). On the pasture, egg transmission
      decreased with the distance from the house: 8 eggs per day in the feeding/dunging
      area (B); 1 egg per day on the nearest pasture (C); <1 egg per day on the distant
      pasture (D). Only a few O. dentatum infections were detected, indicating a poor
      ability of the infective larvae to overwinter. Soil analyses revealed that the
      highest percentage (5.8%) of embryonated A. suum eggs were in the house (A).
      Subsequently, the facility was recontaminated with A. suum eggs by infected pigs.
      A replicate trial 2 was conducted in the following May. A major finding was the
      complete reversal of egg distribution between the 2 years (trials 1 and 2). In
      contrast to previous results, the highest rates of transmission (569 and 480 eggs
      per day) occurred in pasture sections C and D, and the lowest transmission rates
      (192 and 64 eggs per day) were associated with the feeding/dunging sections and
      the house (B and A). Soil analyses again supported the tracer pig results, as the
      pasture sections had the highest concentrations of embryonated eggs. Detailed
      soil analysis also revealed a non-random, aggregated egg distribution pattern.
      The different results of the two trials may be due to the seasonal timing of egg
      deposition and tracer pig exposure. Many eggs deposited during the summer prior
      to trial 1 may have died rapidly due to high temperatures and dessication,
      especially when they were not protected by the house, while deposition in the
      autumn may have favored egg survival through lower temperatures, more moisture,
      and greater sequestration of eggs in the soil by rain and earthworms. The latter
      eggs may, however, not have become embryonated until turnout the next year. The
      results demonstrate that yearly rotations may not be sufficient in the control of
      parasites with long-lived eggs, such as A. suum, and that a pasture rotation
      scheme must include all areas, including housing.

PMID- 11587844
TI  - Biological control of field infections of nematode parasites of young sheep with
      Duddingtonia flagrans and effects of spore intake on efficacy.
AB  - A field study was undertaken to determine the effects of feeding Duddingtonia
      flagrans to young Merino sheep on pasture. A total of 60 mixed sex lambs 4-5
      months old were divided into six even groups on the basis of liveweight. On
      Monday to Friday, each week for 6 months, three groups were offered barley grains
      on which D. flagrans had been cultured while the other three groups remained
      untreated. Every 4 weeks liveweights were recorded and faecal samples collected
      for nematode egg count estimation. Feeding D. flagrans reduced faecal egg counts
      and tended to improve liveweight gains, but considerable differences were
      observed between groups within treatment. These differences are thought to result
      from variations between the groups in consumption of the treated barley with the
      "best" consumers showing the greater effects of treatment.

PMID- 11587845
TI  - Helminths of goats in Mongolia.
AB  - Post-mortem examinations of 236 goats from all provinces in Mongolia were
      performed for the study of helminths in goats. Thirty-nine helminth species
      belonging to three classes, 14 families and 23 genera were found. Trichocephalus
      spiralis and Avitellina centripunctata are reported for the first time in goats
      in Mongolia. The prevalence and intensity of helminth infections are reported for
      three age groups of goats in four seasons and three geographic zones in Mongolia.
      Common helminth infections of goats in all zones of Mongolia were infections of
      Ostertagia, Marshallagia and Nematodirus. In addition, fecal samples of 15 kids,
      15 yearlings and 15 adult goats were examined monthly for eggs. The highest
      number of eggs per gram (EPG) of feces was counted in March (average 1335.3+/
      405.3) and the lowest count was in November (54+/-18.6).

PMID- 11587846
TI  - Comparative analysis of the Band 4.1/ezrin-related protein tyrosine phosphatase
      Pez from two Drosophila species: implications for structure and function.
AB  - The FERM-PTPs are a group of proteins that have FERM (Band 4.1, ezrin, radixin,
      moesin homology) domains at or near their N-termini, and PTP (protein tyrosine
      phosphatase) domains at their C-termini. Their central regions contain either PSD
      95, Dlg, ZO-1 homology domains or putative Src homology 3 domain binding sites.
      The known FERM-PTPs fall into three distinct classes, which we name BAS, MEG, and
      PEZ, after representative human PTPs. Here we analyze Pez, a novel gene encoding
      the single PEZ-class protein present in Drosophila. Pez cDNAs were sequenced from
      the distantly related flies Drosophila melanogaster and Drosophila silvestris,
      and found to be highly conserved except in the central region, which contains at
      least 21 insertions and deletions. Comparison of fly and human Pez reveals
      several short conserved motifs in the central region that are likely protein
      binding sites and/or phosphorylation sites. We also identified novel invertebrate
      members of the BAS and MEG classes using genome data, and generated an alignment
      of vertebrate and invertebrate FERM domains of each class. 'Specialized' residues
      were identified that are conserved only within a given class of PTPs. These
      residues highlight surface regions that may bind class-specific ligands; for PEZ,
      these residues cluster on and near FERM subdomain F1. Finally, the PTP domain of
      fly Pez was modeled based on known PTP tertiary structures, and we conclude that
      Pez is likely a functional phosphatase despite some unusual features of the
      active site cleft sequences. Biochemical confirmation of this hypothesis and
      genetic analysis of Pez are currently underway.

PMID- 11587847
TI  - Multiple isoforms and an unusual cathodic isoform of creatine kinase from channel
      catfish (Ictalurus punctatus).
AB  - In vertebrates, the creatine kinase (CK) family consists of two cytosolic and two
      mitochondrial isoforms. The two cytosolic isoforms are the muscle type (M-CK) and
      the brain type (B-CK). Here we report multiple CK isoenzymes in the diploid
      channel catfish (Ictalurus punctatus) with one unusual cathodic isoform that was
      previously found only in pathological situations in human. The cathodic CK
      isoform existed only in the channel catfish stomach, ovary, and spleen, but not
      in any other species analyzed such as tilapia, smallmouth bass, chicken, or rat.
      Two genes encode the multiple forms of the channel catfish M-CK cDNAs. M-CK1 has
      three alleles, M-CK1.1, M-CK1.2, and M-CK1.3, while M-CK2 has just one allele as
      determined by analysis of 17 cDNA clones and by allele-specific PCR. M-CK1
      encodes a protein of 381 amino acids and the M-CK2 cDNA encodes a protein of 380
      amino acids. The two cDNAs shared an 86% identity and both have the nine
      diagnostic boxes for cytosolic CKs and thus are of cytosolic origin. The M-CK1
      gene was isolated, sequenced, and characterized and its promoter should be useful
      for transgenic research for muscle-specific expression.

PMID- 11587848
TI  - IL1RAPL2 maps to Xq22 and is specifically expressed in the central nervous
      system.
AB  - We report the identification and characterization of a homologue of the IL1RAPL
      transcript which is responsible for a form of X-linked mental retardation
      (MRX34). This new transcript was cloned by analysis of genomic sequences from the
      Xq22 region and was named IL1RAPL2 (Interleukin 1 Receptor Accessory Protein-Like
      2). The two X-linked genes share the same domains, the same exon-intron
      organization and a high degree of similarity at the protein level (70.4%
      similarity). RNA in situ expression studies on mouse embryo tissue section at
      different developmental stages show that Il1rapl2 is specifically expressed in
      the nervous system from embryonic day 12.5. The homologies together with the
      pattern of expression render ILRAPL2 a candidate gene for disorders displaying
      involvement of the CNS, including the MRX loci for which the gene has not been
      identified yet.

PMID- 11587849
TI  - A novel factor required for the SUMO1/Smt3 conjugation of yeast septins.
AB  - SUMO1/Smt3, a ubiquitin-like protein modifier, is known to be conjugated to other
      proteins and modulate their functions in various important processes. Similar to
      the ubiquitin system, SUMO1/Smt3 is activated in an ATP-dependent reaction by
      thioester bond formation with E1 (activating enzyme), transferred to E2
      (conjugating enzyme), and passed to a substrate lysine. It remained unknown,
      however, whether any SUMO1/Smt3 ligases (E3s) are involved in the final transfer
      of this modifier. Here we report a novel factor Siz1 (YDR409w) required for
      septin-sumoylation of budding yeast, possibly acting as E3. Siz1 is a member of a
      new family (Miz1, PIAS3, etc.) containing a conserved domain with a similarity to
      a zinc-binding RING-domain, often found in ubiquitin ligases. In the siz1 mutant
      septin-sumoylation was completely abolished. A conserved cysteine residue in the
      domain was essential for this conjugation. Furthermore, Siz1 was localized at the
      mother-bud neck in the M-phase and physically bound to both E2 and the target
      proteins.

PMID- 11587850
TI  - Multiple hybrid polyketide synthase/non-ribosomal peptide synthetase gene
      clusters in the myxobacterium Stigmatella aurantiaca.
AB  - Many bacterial and fungal secondary metabolites are produced by polyketide
      synthases (PKS) and non-ribosomal peptide synthetases (NRPS). Recently, it has
      been discovered that these modular enzymatic systems can also closely cooperate
      to form natural products. The analysis of the corresponding biosynthetic
      machineries, in the form of hybrid systems, is of special interest for
      combinatorial biosynthesis, because the combination of PKS and NRPS can lead to
      an immense variety of structures that might be produced. During our screening for
      hybrid PKS/NRPS systems from myxobacteria, we scanned the genome of Stigmatella
      aurantiaca DW4/3-1 for the presence of gene loci that encode both the PKS and
      NRPS genes. In addition to the previously characterized myxothiazol system, we
      identified three further hybrid loci, three additional PKS and one further NRPS
      gene locus. These were analyzed by hybridization, physical mapping, PCR with
      degenerate oligonucleotides and sequencing of fragments of the gene clusters. The
      function of these genes was not known but it had already been speculated that one
      compound produced by the strain and detected via HPLC was a secondary metabolite.
      This was based on the observation that its production is dependent on an active
      copy of the phosphopantetheinyl transferase gene mtaA. We show here that one of
      the identified hybrid gene loci is responsible for the formation of this
      secondary metabolite. In agreement with the genetic data, the chemical structure
      resembles a cyclic polypeptide with a PKS sidechain. Our data show that S.
      aurantiaca has a broader genetic capacity to produce natural products than the
      number of compounds isolated from the strain so far suggests.

PMID- 11587851
TI  - Construction of a mini-intein fusion system to allow both direct monitoring of
      soluble protein expression and rapid purification of target proteins.
AB  - Affinity purification of recombinant proteins has been facilitated by fusion to a
      modified protein splicing element (intein). The fusion protein expression can be
      further improved by fusion to a mini-intein, i.e. an intein that lacks an
      endonuclease domain. We synthesized three mini-inteins using overlapping
      oligonucleotides to incorporate Escherichia coli optimized codons and allow
      convenient insertion of an affinity tag between the intein (predicted) N- and C
      terminal fragments. After examining the splicing and cleavage activities of the
      synthesized mini-inteins, we chose the mini-intein most efficient in thiol
      induced N-terminal cleavage for constructing a novel intein fusion system. In
      this system, green fluorescent protein (GFP) was fused to the C-terminus of the
      affinity-tagged mini-intein whose N-terminus was fused to a target protein. The
      design of the system allowed easy monitoring of soluble fusion protein expression
      by following GFP fluorescence, and rapid purification of the target protein
      through the intein-mediated cleavage reaction. A total of 17 target proteins were
      tested in this intein-GFP fusion system. Our data demonstrated that the
      fluorescence of the induced cells could be used to measure soluble expression of
      the intein fusion proteins and efficient intein cleavage activity. The final
      yield of the target proteins exhibited a linear relationship with whole cell
      fluorescence. The intein-GFP system may provide a simple route for monitoring
      real time soluble protein expression, predicting final product yields, and
      screening the expression of a large number of recombinant proteins for rapid
      purification in high throughput applications.

PMID- 11587852
TI  - Functional analysis of promoter activity of murine beta-1,6-N
      acetylglucosaminyltransferase.
AB  - In the mouse, beta-1,6-N-acetylglucosaminyltransferase (IGnT) forms branches in
      poly-N-acetyllactosamines, which are good scaffolds for oncodevelopmental cell
      surface antigens and recognition markers. There are two isoforms of IGnT, IGnT A
      and B, which are produced by alternative splicing of the IGnT gene; the unique
      portion is encoded by exon 1 and common portion is encoded by exons 2 and 3.
      Thus, the expression of each isoform is controlled by a different promoter. Here,
      we identified the regulatory regions of the mouse IGnT A and B genes. The
      promoter regions for IGnT A and B did not contain putative TATA or CAAT boxes,
      but each contained GT boxes. The upstream regulatory region of each gene was
      examined by transient luciferase reporter gene transfection experiments and gel
      mobility shift assay. Promoter activity for each gene was detected in F9
      embryonal carcinoma cells, which express IGnT A and B, but not in N2a cells,
      which do not express the gene. Deletion analysis demonstrated that the regions
      308 bp upstream from the transcriptional initiation site of IGnT A and 430 bp
      upstream from the transcriptional initiation site of IGnT B showed minimal
      promoter activity. Mutation of the single GT box in IGnT A and two GT boxes in
      IGnT B caused marked reduction of the promoter activity. These findings provided
      strong evidence that the GT boxes play crucial roles in transcriptional
      regulation of the genes.

PMID- 11587853
TI  - Transcriptional regulation of the mismatch repair gene hMLH1.
AB  - We have characterized the promoter region of the human gene coding for the MLH1
      mismatch repair protein. The total transcriptional activity of the hMLH1 promoter
      is driven by two positive cis-elements included between nucleotides -300 and 
      220. The upstream element is a canonical CCAAT box, and it is recognized by the
      heterotrimeric transcription factor NF-Y. On the other hand, the downstream
      element is recognized by a nuclear factor of about 120 kDa. Variations in hMLH1
      intracellular levels may influence the surveillance of the genome integrity. The
      identification of the two elements may shad some light on the regulation of the
      transcriptional regulation of hMLH1 expression.

PMID- 11587854
TI  - Structure, chromosomal localization, and expression of the gene for mouse ecto
      mono(ADP-ribosyl)transferase ART5.
AB  - Mono(ADP-ribosyl)transferases regulate the function of target proteins by
      attaching ADP-ribose to specific amino acid residues in their target proteins.
      The purpose of this study was to determine the structure, chromosomal
      localization, and expression profile of the gene for mouse ecto-ADP
      ribosyltransferase ART5. Southern blot analyses indicate that Art5 is a single
      copy gene which maps to mouse chromosome 7 at offset 49.6 cM in close proximity
      to the Art1, Art2a and Art2b genes. Northern blot and RT-PCR analyses demonstrate
      prominent expression of Art5 in testis, and lower levels in cardiac and skeletal
      muscle. Sequence analyses reveal that the Art5 gene encompasses six exons
      spanning 8 kb of genomic DNA. The 5' end of the Art5 gene overlaps with that of
      the Art1 gene. A single long exon encodes the predicted ART5 catalytic domain.
      Separate exons encode the N-terminal leader peptide and a hydrophilic C-terminal
      extension. Sequencing of RT-PCR products and ESTs identified six splice variants.
      The deduced amino acid sequence of ART5 shows 87% sequence identity to its
      orthologue from the human, and 37 and 32% identity to its murine paralogues ART1
      and ART2. Unlike ART1 and ART2, ART5 lacks a glycosylphosphatidylinositol-anchor
      signal sequence and is predicted to be a secretory enzyme. This prediction was
      confirmed by transfecting an Art5 cDNA expression construct into Sf9 insect
      cells. The secreted epitope-tagged ART5 protein resembled rat ART2 in exhibiting
      potent NAD-glycohydrolase activity. This study provides important experimental
      tools to further elucidate the function of ART5.

PMID- 11587855
TI  - Expression profile of active genes in human periodontal ligament and isolation of
      PLAP-1, a novel SLRP family gene.
AB  - Periodontal ligament (PDL) is one of the most important tissues in maintaining
      the homeostasis of tooth and tooth-supporting tissue, periodontium. In this
      study, we investigated the expression profile of active genes in the human PDL
      obtained by collecting sequences with a 3'-directed cDNA library, which
      faithfully represents the composition of the mRNA population. We succeeded in
      obtaining a total of 1752 cDNA sequences by sequencing randomly selected clones
      and identified a total of 1318 different species as gene signatures (GS) by their
      sequence identity, 344 of which were known genes in the GenBank, and 974 of which
      were new genes. The resulting expression profile showed that collagen type I and
      type III were the most abundant genes and that osteogenesis-related proteins,
      such as SPARC/osteonectin and osteoblast specific factor 2, were highly
      expressed. By comparing the expression profile of PDL with 44 profiles similarly
      obtained with unrelated human cell/tissue, nine novel genes, which are probably
      expressed specifically in PDL, were discovered. Among them, we cloned a full
      length cDNA of GS5096, which is frequently expressed in freshly-isolated
      periodontal tissue. We found that it encodes a novel protein, which is a new
      member of the class I small leucine-rich repeat proteoglycan family, and
      designated it PLAP-1 (periodontal ligament associated protein-1). PLAP-1 mRNA
      expression was confirmed in in vitro-maintained PDL cells and was enhanced during
      the course of the cytodifferentiation of the PDL cells into mineralized tissue
      forming cells such as osteoblasts and cementoblasts. These findings suggest the
      involvement of PLAP-1 in the mineralized matrix formation in PDL tissues.

PMID- 11587856
TI  - A subset of Cowdria ruminantium genes important for immune recognition and
      protection.
AB  - Cowdria ruminantium causes the tick-borne rickettsial disease of heartwater,
      which is devastating to livestock production in sub-Saharan Africa. Current
      diagnosis and control methods are inadequate. We have identified and sequenced a
      subset of genes encoding recombinant antigens recognized by antibody and
      peripheral blood mononuclear cells from immune ruminants. The identified genes
      include many with significant similarity to those of Rickettsia prowazekii, genes
      predicted to encode different outer membrane proteins and lipoproteins and a gene
      containing an unusual tandem repeat structure. Evidence is presented for immune
      protection by recombinant antigens in a mouse model of C. ruminantium infection.
      These data identify new recombinant antigens for evaluation in vaccines and
      diagnostic tests to control heartwater.

PMID- 11587857
TI  - Cloning and characterization of murine EDF-1.
AB  - Murine endothelial differentiation-related factor (mEDF-1) encodes a basic
      intracellular protein of 148 amino acids which is highly homologous to the human
      and rat polypeptides. mEDF-1 is expressed in most murine tissues tested and is
      evolutionary conserved. mEDF-1 expression is modulated in mouse development,
      since its expression is high early in development and decreases thereafter.
      Because EDF-1 has been isolated as a gene differentially expressed by exposure of
      endothelial cells to the Tat protein of HIV, we evaluated mEDF-1 expression in
      different cell lines derived from tumors which spontaneously develop in Tat
      transgenic mice. Cells isolated from adenocarcinomas and leiomyosarcomas express
      very high amounts of EDF-1, independently from their capability to secrete Tat.
      Tat transgenic mice also develop skin lesions which closely resemble human
      Kaposi's sarcoma. Since Kaposi spindle cells, which are the proliferative
      component of the sarcoma, differentiate from an endothelial precursor, it is
      noteworthy that spindle cells derived from Kaposi-like lesions of the Tat
      transgenic mice downregulate EDF-1 when compared to microvascular endothelial
      cells isolated from the same tissue.

PMID- 11587859
TI  - Efficient DNA database laboratory strategy for high through-put STR typing of
      reference samples.
AB  - DNA intelligence databases were installed successfully in various countries
      during the past few years. It is a general trend that laboratories performing STR
      analysis for DNA databases have to adjust to increased sample through-put,
      especially when dealing with a high number of reference samples. In contrast to
      routine forensic casework analysis, where samples of suspects and unknown samples
      are interpreted with regard to the specific circumstances of the case and are
      kept distinctly apart from other cases, DNA databases consist of single,
      primarily unlinked DNA profiles. Problems areas associated with the high number
      of anonymous DNA profiles are the risk of logistic errors, such as sample mix-up
      during the laboratory procedure, and the risk of typing errors during manual
      transcription of data and/or results. Thus, DNA databases clearly require new
      laboratory strategies to rise to the challenge. This paper presents an efficient
      automated laboratory strategy on the platform of a laboratory management
      information system (LIMS) with the Austrian DNA Intelligence Database as example.
      Two goals were tackled in particular: first, data safety by avoiding both manual
      interaction during critical laboratory steps (i.e. when DNA is transferred form
      one tube into another), and errors due to manual transcription of sample
      information and results. Secondly, efficient sample processing by automizing the
      laboratory procedure with the help of robotic instruments, thus, giving the DNA
      staff more time to analyze data.

PMID- 11587858
TI  - Characterization of a highly repeated DNA sequence family in five species of the
      genus Eulemur.
AB  - The karyotypes of Eulemur species exhibit a high degree of variation, as a
      consequence of the Robertsonian fusion and/or centromere fission. Centromeric and
      pericentromeric heterochromatin of eulemurs is constituted by highly repeated DNA
      sequences (including some telomeric TTAGGG repeats) which have so far been
      investigated and used for the study of the systematic relationships of the
      different species of the genus Eulemur. In our study, we have cloned a set of
      repetitive pericentromeric sequences of five Eulemur species: E. fulvus fulvus
      (EFU), E. mongoz (EMO), E. macaco (EMA), E. rubriventer (ERU), and E. coronatus
      (ECO). We have characterized these clones by sequence comparison and by
      comparative fluorescence in situ hybridization analysis in EMA and EFU. Our
      results showed a high degree of sequence similarity among Eulemur species,
      indicating a strong conservation, within the five species, of these
      pericentromeric highly repeated DNA sequences.

PMID- 11587860
TI  - Cytochrome b gene for species identification of the conservation animals.
AB  - A partial DNA sequence of cytochrome b gene was used to identify the remains of
      endangered animals and species endemic to Taiwan. The conservation of animals
      species included in this study were: the formosan gem-faced civets, leopard cats,
      tigers, clouded leopards, lion, formosan muntjacs, formosan sika deers, formosan
      sambars, formosan serows, water buffalo, formosan pangolins and formosan
      macaques. The control species used included domestic cats, domestic dogs,
      domestic sheeps, domestic cattles, domestic pigs and humans. Heteroplasmy was
      detected in the formosan macaque, domestic pig and domestic cats. The frequencies
      of heteroplasmy in these animals were about 0.25% (1 in 402bp). Sequences were
      aligned by Pileup program of GCG computer package, and the phylogenetic tree was
      constructed by the neighbor-joining method. The results of sequence comparison
      showed that the percentage range of sequence diversity in the same species was
      from 0.25 to 2.74%, and that between the different species was from 5.97 to
      34.83%. The results of phylogenetic analysis showed that the genetic distance
      between the different species was from 6.33 to 40.59. Animals of the same
      species, both the endangered animal species and domestic animals, were clustered
      together in the neighbor-joining tree. Three unknown samples of animal remains
      were identified by this system. The partial sequence of cytochrome b gene adopted
      in this study proved to be usable for animal identification.

PMID- 11587861
TI  - Sequence structure of 12 novel Y chromosome microsatellites and PCR amplification
      strategies.
AB  - In this work, we present sequencing data for 12 recently reported Y STR loci
      (DYS434, DYS435, DYS436, DYS437, DYS438, DYS439, GATA A10, GATA 7.1, GATA 7.2,
      GATA C4, GATA H4, GATA A4), as well as the PCR multiplex strategies we
      implemented for their detection. Sequenced allelic ladders were constructed and a
      nomenclature for these new systems is proposed based on the sequence structure
      and following ISFG recommendations.GATA A4 and DYS439 are likely the same STR.
      They have the same STR structure and the alleles are always the same in the same
      individuals.Sequence polymorphisms were observed in the GATA C4 and DYS437 STRs.
      The variation in DYS437 was associated with a specific population group and is
      very interesting not only for forensic genetics but also for anthropological
      studies.

PMID- 11587862
TI  - A dot-blot-immunoassay for semen identification using a polyclonal antibody
      against semenogelin, a powerful seminal marker.
AB  - Among various seminal plasma proteins, semenogelin (Sg), produced in the seminal
      vesicle, has been considered a candidate for demonstrating the presence of semen.
      Sg consists of two proteins, one 52 kDa (Sg-I) in size, and the other a mixture
      of 71 and 76 kDa proteins (Sg-II). Recombinant Sg-I and Sg-II proteins were
      obtained using a baculovirus system and then injected into a rabbit to produce
      the respective antibodies [Characterization of recombinant precursor proteins of
      the human seminal plasma sperm motility inhibitor synthesized in insect cells,
      Int. J. Mol. Med. 2 (1998) 693]. When liquefied seminal plasma was immunoblotted
      with the anti-Sg-I and Sg-II antibodies, the anti-Sg-II antibody identified a
      wider range of the polypeptides originating from Sg than did the anti-Sg-I
      antibody. A dot-blot-immunoassay using anti-Sg-II antibody revealed a clear
      immunoreactive spot even when the semen was diluted 6400-fold. However, this
      assay showed that the Sg antigen was undetectable in saliva, urine, vaginal
      secretions, sweat, nasal secretions and serum. To determine the stability of Sg
      antigenic activity, filter paper with dried semen stains were kept at 37, 4 and
      22 degrees C for 1, 6 and 18 months, respectively, and the Sg antigenic activity
      was examined. The activity was detectable in an area not less than 0.5 cm x 0.5
      cm under all of the above environmental conditions during each period. Finally,
      semen was mixed with saliva or blood at various volumetric ratios, and used as a
      source of dried stains. The Sg antigenic activity was detectable in the stains
      until the ratio of semen to saliva or blood reached 1:8. These results suggest
      that Sg may be useful as a marker for semen identification.

PMID- 11587863
TI  - Differentiation between used motor oils on the basis of their IR spectra with
      application of the correlation method.
AB  - Two brands of motor oils (Elf and Castrol) that had been used for various periods
      of time were examined. The aim was to differentiate these samples (of varying
      degree of use) on the basis of their infrared spectra, for criminalistic
      purposes. The correlation method was used. It was found that the FTIR method is
      capable of providing sufficiently detailed information if some specific fragments
      of spectra are examined. Hence, it can be concluded that the investigation
      procedure proposed is adequate.

PMID- 11587864
TI  - GC-MS determination of gamma-hydroxybutyric acid (GHB) in blood.
AB  - A sensitive and specific gas chromatography-mass spectrometer (GC-MS) method
      using selective ion monitoring (SIM) has been developed for the quantification of
      gamma-hydroxybutyric acid (GHB) in blood. This method uses liquid-liquid
      extraction and disilyl-derivatization, without conversion to the gamma
      butyrolactone (GBL), followed by GC-MS analysis using GHB-d6 as the internal
      standard. The method was linear from 0.1 to 20 mg/dl, and the limit of
      quantification using 50 microl of blood was determined to be 0.1 mg/dl.

PMID- 11587865
TI  - Clocapramine-related fatality. Postmortem drug levels in multiple psychoactive
      drug poisoning.
AB  - A suicide caused by ingestion of multiple psychoactive drugs is reported. A 42
      year-old man with a history of psychosis was found dead in a blood pool in his
      room. The forensic autopsy revealed two stab wounds on his chest. However, these
      wounds could not explain the cause of death. Eighty-six tablets were found in his
      stomach. Four psychoactive drugs; clocapramine (CC), chlorpromazine (CP),
      promethazine (PM) and clotiazepam (CT) were detected in blood and tissues. The
      concentrations of CC, CP, PM and CT in the femoral vein (FV) blood were 0.39,
      0.61, 1.23 and 0.09 microg/ml, respectively. The cause and manner of death were
      attributed to suicidal multiple psychoactive drug poisoning. Postmortem drug
      redistribution showed great site-dependent variations with the lowest level in
      the FV blood. Remarkable variations were observed in CC, CP and PM, but not in CT
      compared to other three drugs. The variations were dependent on the volume of
      distribution (Vd) of the drugs. Our human case has demonstrated drugs with higher
      Vd values showed higher degree of postmortem redistribution of the drug and vice
      versa.

PMID- 11587866
TI  - Drug related deaths in the Strathclyde region of Scotland, 1995-1998.
AB  - The misuse of drugs, both illicit and prescribed has increased dramatically in
      the west of Scotland over the last few decades. Consequently, the number of drug
      related deaths has risen as a direct result. Since, discrepancies exist between
      data collected by the Department of Forensic Medicine and Science, University of
      Glasgow and official statistics, this project, was funded to investigate all
      known drug related deaths that occurred within the Strathclyde region of Scotland
      in an effort to improve the accuracy of statistics and the dissemination of
      information pertaining to them. Changes in medical treatment, legislation and
      patterns of drug taking were noted and the effects of these on the year-by-year
      death tolls evaluated.

PMID- 11587867
TI  - Fatal myeloencephalopathy due to accidental intrathecal vincristin
      administration: a report of two cases.
AB  - We report on two fatal cases of accidental intrathecal vincristine instillation
      in a 5-year old girl with recurrent acute lymphoblastic leucemia and a 57-year
      old man with lymphoblastic lymphoma. The girl died seven days, the man four weeks
      after intrathecal injection of vincristine. Clinically, the onset was
      characterized by the signs of opistothonus, sensory and motor dysfunction and
      ascending paralysis. Histological and immunohistochemical investigations (HE-LFB,
      CD-68, Neurofilament) revealed degeneration of myelin and axons as well as
      pseudocystic transformation in areas exposed to vincristine, accompanied by
      secondary changes with numerous prominent macrophages. The clinical course and
      histopathological results of the two cases are presented. A review of all
      reported cases in the literature is given. A better controlled regimen for
      administering vincristine and intrathecal chemotherapy is recommended.

PMID- 11587868
TI  - Comparison of urine to sweat patch test results in court ordered testing.
AB  - A former cocaine and methamphetamine abuser was continuously monitored with both
      sweat patch and urine testing for approximately 6 months. Thirteen sweat patches
      were applied and collected, five were positive for cocaine and/or
      methamphetamine, but all the urine specimens collected were negative at the
      analytical cut-off levels. The high incidence of false positive sweat patch tests
      in relation to the sensitivity, specificity, and efficiency of the sweat patch
      assay is discussed. Possible mechanisms, which can lead to false positive
      results, are presented. The results of our study raise further questions about
      the preferential use of the sweat patch in detecting new episodes of drug use in
      formerly chronic drug users.

PMID- 11587869
TI  - Fatal intoxication due to excessive dichloromethane inhalation.
AB  - A 22-year-old white male was found dead at his working place in a car lacquering
      company. He had removed lacquer residues by using a solvent containing
      dicloromethane (DCM) without using a gas mask. Pathology revealed signs of
      asphyxiation with obvious petechial bleedings and expressed microthrombosis of
      the pulmonary arteries. Toxicological analysis showed excessive concentrations of
      DCM which are inhaled due to exposure of extreme air concentrations.

PMID- 11587870
TI  - Traffic injury or attempted infanticide?
AB  - Two sewing needles were found in a woman's cranial cavity by X-ray examination
      after she had sustained traffic injury. After investigation and analysis, it has
      been confirmed that the sewing needles were inserted by others when she was an
      infant, and not by the traffic injury.

PMID- 11587871
TI  - A forensic classification of distortion in human bite marks.
AB  - The occurrence of distortion in human bite marks is well recognised. A forensic
      classification of distortion is suggested which is based upon the causative
      factors and their inter-relationships. The terms primary distortion and secondary
      distortion are introduced and described. The objective of this classification is
      to emphasise the need for a scientific approach to the recognition and
      interpretation of the types of distortion found in human bite marks. The
      relationships between distortion, distinctive features and superimposition
      techniques in bite mark analysis are discussed.

PMID- 11587872
TI  - Basal ganglia dysfunction in Tourette's syndrome: a new hypothesis.
AB  - Tourette's syndrome is a neuropsychiatric syndrome with onset in childhood that
      is characterized by chronic multiple tics. The cause of Tourette's syndrome is
      unknown, but the pathophysiology most likely involves basal ganglia and
      frontocortical circuits. A useful scheme of basal ganglia dysfunction should be
      able to account for the features that make Tourette's syndrome unique, in
      addition to the features that Tourette's syndrome shares with other disorders.
      Recent advances in knowledge of basal ganglia functional anatomy and physiology
      make it possible to hypothesize how specific neural mechanisms relate to specific
      clinical manifestations of Tourette's syndrome. A model of selection and
      suppression of competing behaviors by the basal ganglia is presented. The
      functional anatomy of basal ganglia circuits and new information on dopamine
      modulation of those circuits provide the basis for hypotheses of basal ganglia
      dysfunction in Tourette's syndrome.

PMID- 11587873
TI  - Antiepileptic drugs: affective use in autism spectrum disorders.
AB  - Antiepileptic drugs are widely administered to individuals with autistic spectrum
      disorders. There are several reasons for the use of antiepileptic drugs in
      autistic spectrum disorders, including the high incidence of epilepsy in these
      individuals, the anecdotal reports suggesting an improvement of communication and
      behavior in autistic subjects with epileptic discharges, and the increased
      awareness that some disruptive behaviors may be manifestations of an associated
      affective disorder. In this study, data on the current use of antiepileptic drugs
      in the treatment of autism, and on the association of affective disorders with
      epilepsy and autism, are reviewed. The evidence supporting the hypothesis that
      there may be a subgroup of autistic children with epilepsy and affective
      disorders that preferentially respond to antiepileptic drugs is still very
      preliminary, and further investigations with double-blind controlled studies are
      needed. Although the role of antiepileptic drugs at the present time is not
      established, there is evidence that autism, epilepsy, and affective disorders
      commonly co-occur, and that they may share a common neurochemical substrate,
      which is the common target of the psychotropic mechanism of action of different
      antiepileptic drugs.

PMID- 11587874
TI  - Efficacy of the ketogenic diet in focal versus generalized seizures.
AB  - Most reports of the ketogenic diet have focused on its efficacy for generalized
      seizures. Few data are available regarding its effect on focal seizures. We
      retrospectively studied patients (mean = 7.5 years of age) with medically
      intractable epilepsy treated by the ketogenic diet. The predominant seizure types
      in each patient were classified as generalized (100 patients) or focal (34
      patients) based on ictal electroencephalograms (EEGs) or seizure semiology and
      interictal EEG. A seizure reduction of more than 50% compared with baseline was
      seen in nine patients (27%) with focal seizures and 46 patients (46%) with
      generalized seizures at 3 months, in 10 patients (30%) with focal seizures and 46
      patients (46%) with generalized seizures at 6 months, and in eight patients (24%)
      with focal seizures and 42 patients (42%) with generalized seizures at 12 months.
      Differences were not significant. Outcome tended to be better in patients younger
      than 12 years of age compared with the older age group, but the difference was
      significant at 6 months only. Our results suggest that some patients with
      intractable focal epilepsy may respond favorably to the ketogenic diet and that
      this option should be considered if epilepsy surgery is not possible.

PMID- 11587875
TI  - Vagal nerve stimulation in tuberous sclerosis complex patients.
AB  - This is an open-label, retrospective, multicenter study to determine the outcome
      of intermittent stimulation of the left vagal nerve in children with tuberous
      sclerosis complex and medically refractory epilepsy. The records of all children
      treated with vagal nerve stimulation were reviewed in five pediatric epilepsy
      centers to locate those with tuberous sclerosis complex who had been treated with
      vagal nerve stimulation for at least 6 months. These patients were compared with
      (1) a series of patients obtained from the literature, (2) 10 similar control
      patients with epilepsy obtained from a registry of patients receiving vagal nerve
      stimulation, and (3) four published series of tuberous sclerosis complex patients
      whose epilepsy was surgically managed. Ten tuberous sclerosis complex patients
      with medically refractory epilepsy treated with vagal nerve stimulation were
      found. Nine experienced at least a 50% reduction in seizure frequency, and half
      had a 90% or greater reduction in seizure frequency. No adverse events were
      encountered. Comparison with published and registry patients revealed improved
      seizure control in the tuberous sclerosis complex patients. Comparison with the
      group undergoing seizure surgery demonstrated improved outcomes after surgery.
      Vagal nerve stimulation appears to be an effective and well-tolerated adjunctive
      therapy in patients with tuberous sclerosis complex and seizures refractory to
      medical therapy. Resective surgery has a better prospect for improved seizure
      control.

PMID- 11587876
TI  - Neurologic outcomes of pediatric epileptic patients with pentobarbital coma.
AB  - Status epilepticus is a life-threatening condition requiring emergent medical
      attention. Although initial therapies with antiepileptic drugs generally
      terminate seizures within 30 to 60 minutes, patients with refractory status
      epilepticus require additional intervention. High-dose pentobarbital has been the
      most commonly prescribed agent for the management of refractory status
      epilepticus in children. The objective of this research was to evaluate the
      association between the response of pentobarbital coma and neurologic outcomes in
      refractory status epilepticus. Twenty-three subjects were treated with
      pentobarbital coma for at least 48 hours. Medical records were reviewed to
      collect patient demographic information, responses to treatment, and neurologic
      outcomes. Among the 23 patients reviewed, 12 patients were controlled with
      pentobarbital (responders), six were unresponsive to pentobarbital
      (nonresponders), and five patients relapsed after discontinuation or during
      tapering of pentobarbital (relapser). The mortality rate among the relapser and
      nonresponder groups combined was 90.9%, but no deaths occurred among the
      responder group (P < 0.001). The survival rate was greater among toddlers
      compared with neonates or older children. Failure of seizure control after
      pentobarbital coma was associated with a poor prognosis. The potential for
      serious complications of pentobarbital therapy among neonates highlights the need
      for careful dosing in this age group.

PMID- 11587877
TI  - Characteristic neuropathology and plasticity in periventricular leukomalacia.
AB  - The brains of extremely low-birth-weight infants with periventricular
      leukomalacia, who survived for more than 30 days, were examined by means of
      neuropathologic and immunohistochemical methods. The characteristic
      neuropathology of the brain is comprised of spongy changes with astrogliosis, a
      widespread distribution (i.e., in the deep to intermediate white matter), and a
      diffuse distribution of associated recent lesions. Also, these lesions, both
      remote and recent, are located in the frontal to occipital lobes. Regarding the
      correlation between the lesions and transneuronal connecting fibers, the lesions
      involved fibers of the motor, sensory, visual, and higher cerebral functions.
      This involvement may cause motor and intellectual disabilities. Furthermore,
      immunohistochemistry demonstrated nestin-positive astrocytes, and neurons
      increased around the lesions, suggesting the plasticity of the brains.

PMID- 11587878
TI  - The spectrum of neurologic disease in children with systemic cancer.
AB  - To determine the range of neurologic complications in children with systemic
      cancer, we evaluated prospectively all of the neurologic consultations requested
      by the pediatric department of Memorial Sloan-Kettering Cancer Center from
      October 1997 until January 2001. Demographic data, main complaints, diagnosis,
      cancer status, etiology, and neuroradiologic studies were reviewed for the 528
      consultations. Headache was the most frequent complaint (18.3%), followed by
      altered mental status (8.4%) and back pain (7.1%). Many children with these
      complaints had underlying structural disorders despite a normal neurologic
      examination. The symptoms varied with the underlying cancer and tumor status.
      Headaches were more common in patients with hematologic cancers, and back pain
      was more common in patients with solid tumors. Chronic headaches were frequent in
      patients in remission. Iatrogenic complications, particularly related to
      chemotherapy, constituted the largest etiologic group (27.7%). A high percentage
      of neuroradiologic studies were abnormal, and 63% of the magnetic resonance
      imagine studies were diagnostic. The broad spectrum of conditions underlying the
      neurologic complaints of children with systemic cancer illustrates the complexity
      of problems presented by these patients and requires a thorough knowledge of
      pediatric cancer, its effects on the nervous system, and the complications of its
      treatment from the neurology consultant.

PMID- 11587879
TI  - Multiple cerebral arteriovenous fistulas and malformations in the neonate.
AB  - Multiple cerebral arteriovenous fistulas with malformations in the fetus or
      neonate are rare. Here we describe a patient who had these lesions with pulmonary
      stenosis, resulting in severe brain atrophy in utero and intractable heart
      failure after birth. The pathophysiology of this patient is discussed in
      hemodynamic terms.

PMID- 11587880
TI  - Kawasaki disease with predominant central nervous system involvement.
AB  - A 4-year-old female was hospitalized with clinical and electroencephalographic
      evidence of acute encephalopathy. Five days later the classic signs of Kawasaki
      disease appeared. The neurologic outcome in this female was poor despite early
      treatment with immunoglobulin. Like many other vasculitidies, Kawasaki disease
      can have predominant neurologic symptoms as the initial presentation and during
      the subsequent evolution of the condition.

PMID- 11587881
TI  - Pre-eclampsia: a predisposing factor for neonatal venous sinus thrombosis?
AB  - Neonatal venous sinus thrombosis is a well-recognized, but infrequently
      diagnosed, cause of neonatal encephalopathy. Previous reports have tended to omit
      reference to the importance of maternal factors in predisposing the infant to
      this condition. This report, in which eight patients with neonatal venous sinus
      thrombosis are presented, will reveal a strong association between pre-eclampsia,
      prothrombotic disorders, and neonatal venous sinus thrombosis. Contrary to
      previously published reports, there is a high likelihood of neurodevelopmental
      residua after this condition.

PMID- 11587882
TI  - Asymmetric arthrogryposis multiplex congenita with focal pachygyria.
AB  - A male infant with predominantly right-sided arthrogryposis multiplex congenita
      is presented. His posture in the lower extremities was asymmetric, and left
      thoracic scoliosis was present. This patient also manifested focal pachygyria
      dominantly affecting the contralateral cerebral hemisphere and hypoplasia of the
      corpus callosum, brainstem, and cerebellar vermis. Generalized tonic seizures
      began at 2 months of age, and an electroencephalogram revealed epileptic
      discharge. Biopsy of the right biceps revealed a nonspecific change. A direct
      causal relationship between neuronal migration disorders and arthrogryposis
      multiplex congenita has not been established, but considering the abnormal
      neuronal migration along the entire neural axis in focal pachygyria, the
      predominantly right-sided arthrogryposis in this patient was speculated to be
      closely related to the pachygyria of the frontal and temporal lobes dominantly
      affected in the left cerebral hemisphere.

PMID- 11587883
TI  - Spontaneous carotid and vertebral artery dissection in children.
AB  - Carotid and vertebral artery dissection is a rarely reported cause of stroke in
      childhood and adolescence, especially if there is not a direct trauma to the
      neck. Four patients, under 15 years of age, presented with an internal carotid
      artery dissection, and one patient presented with a vertebral artery dissection.
      They were all making a physical effort when the event occurred. The five patients
      had ischemic symptoms, and in two the events were preceded by transient ischemic
      attacks. Headache was associated in four patients. The diagnosis was made by
      magnetic resonance imaging and angiography, which included transfemoral
      angiography in two patients. All improved before leaving the hospital, and four
      patients did not suffer recurrent episodes. The diagnostic accuracy of artery
      dissection has improved because of noninvasive neuroimaging testing, but it
      should still be suspected in any pediatric ischemic stroke, especially if there
      is headache or cervical pain associated.

PMID- 11587884
TI  - Extraneurologic symptoms as presenting signs of Sanfilippo disease.
AB  - Sanfilippo disease, or mucopolysaccharidosis type III, results from the
      deficiency of lysosomal hydrolases, which impairs heparan sulfate metabolism.
      Clinically, the disease is characterized by a mild somatic phenotype combined
      with early severe neurodegenerative illness with prominent behavioral
      disturbance. We report clinical and molecular findings of a child with Sanfilippo
      disease type B (alpha-N>-acetylglucosaminidase deficiency) who presented at age
      18 months with marked systemic involvement and normal initial psychomotor
      development. These findings suggest that atypical mucopolysaccharidosis type III
      patients may present with early somatic changes preceding the onset of overt
      neurologic symptoms and ensuring an early diagnosis and possible therapeutic
      intervention.

PMID- 11587885
TI  - Quetiapine--efficacy in different domains.
AB  - Conventional treatment paradigms for schizophrenia have typically focused on
      reducing positive symptomatology; however, it is increasingly apparent that
      negative and cognitive symptoms are also important treatment targets. Cognitive
      function, in particular, is known to affect multiple outcome domains, including
      performance of basic daily activities, and social and occupational functioning.
      While traditional antipsychotics have little, or even a detrimental, effect on
      neurocognitive impairment in patients with schizophrenia, available data suggest
      that cognitive function may be improved during treatment with atypical
      antipsychotics. Quetiapine is a novel atypical antipsychotic with proven efficacy
      in schizophrenia across all domains. Results of well-controlled, double-blind,
      randomised studies show quetiapine to significantly improve cognitive function
      compared with treatment with haloperidol. Quetiapine has also been shown to be
      effective and well tolerated in patients particularly vulnerable to the
      extrapyramidal side effects (EPS) associated with conventional antipsychotics,
      making it well suited for use as first-line therapy.

PMID- 11587886
TI  - Good tolerability equals good results: the patient's perspective.
AB  - Although conventional antipsychotics are useful for the treatment of
      schizophrenia, many patients discontinue taking them within a few months. As well
      as the positive influence of a good doctor-patient relationship, evidence
      suggests that the patient's initial subjective experience during antipsychotic
      therapy is a major predictor of compliance. In addition to motor symptoms,
      conventional antipsychotics can cause significant adverse effects on drive,
      emotion and cognition, which are reflected in patients complaining of a reduced
      quality of life, although may not be detected by objective examination. This
      syndrome, which is similar to the negative symptoms of schizophrenia, is known by
      numerous terms including 'pharmacogenic depression' and 'pharmacogenic
      anhedonia'. The introduction of atypical antipsychotics broadened the criteria
      for effective antipsychotic treatment to include the subjective assessment of
      improvement in patients' quality of life. The previous lack of interest in this
      domain may have been due to the inability to improve it with conventional agents
      and the misconception that schizophrenic patients were unable to subjectively
      evaluate their quality of life. However, numerous studies have shown that 63-95%
      of patients in remission are able to self-rate their affective state of well
      being or quality of life. Atypical antipsychotics are superior to conventional
      antipsychotics in improving quality of life and reducing the stigma of
      schizophrenia, particularly from the patient's perspective and are strong reasons
      for the widespread use of these drugs.

PMID- 11587887
TI  - Extrapyramidal side effects are unacceptable.
AB  - Extrapyramidal side effects (EPS) are a common and serious drawback to the use of
      conventional antipsychotic drugs. In addition to the discomfort and distress
      caused to patients, EPS may contribute to poor compliance and ultimately poor
      treatment outcome. The results of clinical trials with the new generation of
      atypical antipsychotics suggest that they are associated with a reduction in both
      early- and late-occurring EPS. All of the new-generation agents produce
      substantially fewer EPS, and reduce the need for antiparkinsonian medication, in
      comparison with haloperidol. Data from long-term studies suggest that new
      generation antipsychotics are also associated with a reduced risk of tardive
      dyskinesia, particularly in the elderly.

PMID- 11587888
TI  - Quetiapine: efficacy and tolerability in schizophrenia.
AB  - Quetiapine, in common with clozapine, has a greater affinity for 5-HT(2)
      receptors than D(2) receptors and preclinical studies have consistently predicted
      efficacy against schizophrenia, with a low potential for causing extrapyramidal
      symptoms (EPS). In clinical trials, the efficacy of quetiapine was consistently
      superior to placebo and it was effective against both positive and negative
      symptoms. Quetiapine was also at least as effective as chlorpromazine or
      haloperidol in improving the symptoms of acute schizophrenia and moreover was
      associated with higher response rates. The consistent, placebo-level incidence of
      EPS associated with quetiapine in clinical trials was not seen with haloperidol.
      Thus, the combination of efficacy comparable to other antipsychotic agents, with
      an acceptable side effect and tolerability profile, provides support for the use
      of quetiapine as a first-line antipsychotic agent in the long-term treatment of
      schizophrenia.

PMID- 11587889
TI  - Auditory perception of laughing and crying activates human amygdala regardless of
      attentional state.
AB  - Adequate behavioral responses to socially relevant stimuli are often impaired
      after lesions of the amygdala. Such lesions concern especially the recognition of
      facial and sometimes of vocal expression of emotions. Using low-noise functional
      magnetic resonance imaging (fMRI), we investigated in which way the amygdala,
      auditory cortex and insula are involved in the processing of affective nonverbal
      vocalizations (Laughing and Crying) in healthy humans. The same samples of male
      and female Laughing and Crying were presented in different experimental
      conditions: Simply listening to the stimuli, self-induction of the corresponding
      emotions while listening, and detection of artificial pitch shifts in the same
      stimuli. All conditions activated the amygdala similarly and bilaterally, whereby
      the amount of activation was larger in the right amygdala. The auditory cortex
      was more strongly activated by Laughing than by Crying with a slight right
      hemisphere advantage for Laughing, both likely due to acoustic stimulus features.
      The insula was bilaterally activated in all conditions. The mean signal intensity
      change with stimulation was much larger in the amygdala than in auditory cortex
      and insula. The amygdala results seem to be in accordance with the right
      hemisphere hypothesis of emotion processing which may not be applicable as
      strongly to the level of auditory cortex or insula.

PMID- 11587890
TI  - Encoding and retrieval related cerebral activation in continuous verbal
      recognition.
AB  - The differential neuronal activation related to encoding of novel and recognition
      of previously studied items and the effect of retrieval effort on neuronal
      activation were assessed in a event-related functional magnetic resonance imaging
      experiment. A verbal continuous recognition task with two repetitions of the
      target items was used. The interpretation of the results was focused on brain
      areas that have been previously reported to be involved in explicit memory.
      Encoding of novel words in comparison with the first repetition was associated
      with a stronger activation in the left parahippocampal and inferior frontal
      gyrus. Encoding of novel words compared to the second repetition was related to a
      greater bifrontal activation. Recognition of studied items was associated with
      greater activation in the medial and bilateral inferior parietal lobe at first
      repetition and in the medial and left inferior parietal lobe at second repetition
      in comparison with encoding of the novel items. Recognition at first repetition
      compared to recognition at second repetition was associated with greater
      bilateral frontal activation. The results are discussed in relation to current
      concepts of spatial differentiation of memory function and findings from event
      related potentials studies of continuous recognition.

PMID- 11587891
TI  - Neural correlates of advance movement preparation: a dipole source analysis
      approach.
AB  - This study examined cortical motor structures that are involved in preprogramming
      and execution of movements. In two independent experiments a response precuing
      task was employed that combined the recording of movement-related brain
      potentials (MRPs) with spatio-temporal source localization. Behavioral and MRP
      results indicated the utilization of advance information about movement direction
      and hand. Dipole source modeling of foreperiod MRPs revealed a reliable three
      dipole solution with sources located in lateral and medial brain regions anterior
      to the precentral gyrus. These dipoles were located in the lateral premotor area
      (PMA) and supplementary/cingulate motor areas (SMA/CMA). Activity of the medial
      dipole increased with the extent of advance motor preparation, whereas lateral
      dipole activity revealed parallel preparation of both response hands when only
      partial information about movement direction was available. The dissociation in
      the strength and the onset of medial and lateral dipole activity indicated two
      phases of motor preparation. We propose that medial motor areas like SMA and CMA
      are involved in the assembling and selection of abstract movement programs,
      whereas lateral PMA and primary motor cortex are involved in effector-specific
      motor preparation.

PMID- 11587892
TI  - Attention to emotion modulates fMRI activity in human right superior temporal
      sulcus.
AB  - A parallel neural network has been proposed for processing various types of
      information conveyed by faces including emotion. Using functional magnetic
      resonance imaging (fMRI), we tested the effect of the explicit attention to the
      emotional expression of the faces on the neuronal activity of the face-responsive
      regions. Delayed match to sample procedure was adopted. Subjects were required to
      match the visually presented pictures with regard to the contour of the face
      pictures, facial identity, and emotional expressions by valence (happy and
      fearful expressions) and arousal (fearful and sad expressions). Contour matching
      of the non-face scrambled pictures was used as a control condition. The face
      responsive regions that responded more to faces than to non-face stimuli were the
      bilateral lateral fusiform gyrus (LFG), the right superior temporal sulcus (STS),
      and the bilateral intraparietal sulcus (IPS). In these regions, general attention
      to the face enhanced the activities of the bilateral LFG, the right STS, and the
      left IPS compared with attention to the contour of the facial image. Selective
      attention to facial emotion specifically enhanced the activity of the right STS
      compared with attention to the face per se. The results suggest that the right
      STS region plays a special role in facial emotion recognition within distributed
      face-processing systems. This finding may support the notion that the STS is
      involved in social perception.

PMID- 11587893
TI  - Cortical substrates for the perception of face actions: an fMRI study of the
      specificity of activation for seen speech and for meaningless lower-face acts
      (gurning).
AB  - Can the cortical substrates for the perception of face actions be distinguished
      when the superficial visual qualities of these actions are very similar? Two fMRI
      experiments are reported. Compared with watching the face at rest, observing
      silent speech was associated with bilateral activation in a number of temporal
      cortical regions, including the superior temporal sulcus (STS). Watching face
      movements of similar extent and duration, but which could not be construed as
      speech (gurning; Experiment 1b) was not associated with activation of superior
      temporal cortex to the same extent, especially in the left hemisphere. Instead,
      the peak focus of the largest cluster of activation was in the posterior part of
      the inferior temporal gyrus (right, BA 37). Observing silent speech, but not
      gurning faces, was also associated with bilateral activation of inferior frontal
      cortex (BA 44 and 45). In a second study, speechreading and observing gurning
      faces were compared within a single experiment, using stimuli which comprised the
      speaker's face and torso (and hence a much smaller image of the speaker's face
      and facial actions). There was again differential engagement of superior temporal
      cortex which followed the pattern of Experiment 1. These findings suggest that
      superior temporal gyrus and neighbouring regions are activated bilaterally when
      subjects view face actions--at different scales--that can be interpreted as
      speech. This circuitry is not accessed to the same extent by visually similar,
      but linguistically meaningless actions. However, some temporal regions, such as
      the posterior part of the right superior temporal sulcus, appear to be common
      processing sites for processing both seen speech and gurns.

PMID- 11587894
TI  - Neuroelectrical signs of selective attention to color in boys with attention
      deficit hyperactivity disorder.
AB  - In order to gain insight into the functional and macroanatomical loci of visual
      selective processing deficits that may be basic to attention-deficit
      hyperactivity disorder (ADHD), the present study examined multi-channel event
      related potentials (ERPs) recorded from 7- to 11-year-old boys clinically
      diagnosed as having ADHD (n=24) and age-matched healthy control boys (n=24) while
      they performed a visual (color) selective attention task. The spatio-temporal
      dynamics of several ERP components related to attention to color were
      characterized using topographic profile analysis, topographic mapping of the ERP
      and associated scalp current density distributions, and spatio-temporal source
      potential modeling. Boys with ADHD showed a lower target hit rate, a higher false
      alarm rate, and a lower perceptual sensitivity than controls. Also, whereas color
      attention induced in the ERPs from controls a characteristic early frontally
      maximal selection positivity (FSP), ADHD boys displayed little or no FSP.
      Similarly, ADHD boys manifested P3b amplitude decrements that were partially
      lateralized (i.e., maximal at left temporal scalp locations) as well as affected
      by maturation. These results indicate that ADHD boys suffer from deficits at both
      relatively early (sensory) and late (semantic) levels of visual selective
      information processing. The data also support the hypothesis that the visual
      selective processing deficits observed in the ADHD boys originate from deficits
      in the strength of activation of a neural network comprising prefrontal and
      occipito-temporal brain regions. This network seems to be actively engaged during
      attention to color and may contain the major intracerebral generating sources of
      the associated scalp-recorded ERP components.

PMID- 11587895
TI  - Evaluating a split processing model of visual word recognition: effects of word
      length.
AB  - A new theory of visual word recognition is based on the fact that the fovea is
      split in humans. When a reader fixates the center of a written word, the initial
      letters of the word that are to the left of fixation are projected first to the
      right cerebral hemisphere (RH) while the final letters are projected to the left
      cerebral hemisphere (LH). This paper explores the possibility that this has
      consequences for the early processing of the beginning and ends of centrally
      fixated words: specifically that lexical decision RTs are affected by the number
      of letters to the left of fixation but not by the number of letters to the right
      of fixation. For centrally presented five- and eight-letter words, we manipulated
      number of letters presented to the right or to the left of a fixation point
      (Experiment 1). We found that longer latencies to longer letter strings
      characterised the processing of the initial letters of words while LH word
      recognition features characterised the ends of words. Experiment 2 was a
      lateralized version of Experiment 1, and revealed the well established visual
      field and word length interaction. The results supported the split fovea theory.

PMID- 11587897
TI  - The effect of retrieval cues on post-retrieval monitoring in episodic memory: an
      electrophysiological study.
AB  - The aim of the present experiment was to examine whether episodic retrieval and
      'post-retrieval' monitoring are affected by the nature of the cue that guides a
      search of memory. We recorded event-related brain potentials (ERPs) from young
      healthy adult participants while they tried to recall studied words (e.g.
      'MOTHER') with the aid of word-stem (e.g. 'MOT') and word-fragment (e.g. 'M-TH-
      ') retrieval cues. Analyses of the behavioural data showed that while it was far
      more difficult to generate completions per se for the fragments, the levels of
      conscious, or 'explicit', recall obtained with each type of cue were
      statistically identical. ERP analyses focussed upon differences in neural
      activity evoked by each type of cue (termed 'old/new' ERP effects) during
      successful versus unsuccessful retrieval. The stem and fragment old/new ERP
      effects were remarkably similar in their time course and magnitude, and also in
      their scalp distribution, which changed over time as multiple neuronal
      populations, and hence multiple cognitive operations, became activated. These
      behavioural and ERP findings suggest that the cognitive operations reflected by
      old/new effects in cued recall tasks may be insensitive to changes in the
      retrieval strategy, or effort, that participants apply to monitor the episodic
      status of retrieved information. The findings are discussed in relation to
      previous ERP and functional imaging studies that have investigated task-specific
      features of retrieval and post-retrieval processing in episodic memory.

PMID- 11587896
TI  - A psychophysical study of the relationship between temporal processing in odor
      mixtures and transduction pathways.
AB  - Depending on the odorant, transduction during the olfactory reception process is
      reported to be mediated by the second messengers cyclic adenosine 3',5'
      monophosphate (cAMP) or inositol 1,4,5-triphosphate (IP(3)). The present study
      with humans investigates the relationship between temporal processing in mixtures
      and the type of transduction process used. The most common outcomes were
      reciprocal temporal interactions which were primarily dependent on odorant
      concentration and independent of the type of transduction process. The results
      are consistent with the bulk of evidence that each receptor neuron commonly has
      only one type of receptor.

PMID- 11587898
TI  - Visual error is the stimulus for saccade gain adaptation.
AB  - Saccade accuracy is fundamental to clear vision. The brain maintains saccade
      accuracy by altering commands for saccades that are consistently inaccurate. For
      example, saccades that consistently overshoot their targets gradually become
      smaller. The signal that drives the adaptation of saccade size is not well
      understood. Previous reports propose that corrective movements and visual errors,
      both generated after inaccurate saccades, could be responsible for a change in
      saccade size. Here we show that we can elicit normal reductions in saccade size
      while eliciting few or no correction saccades. These normal reductions in saccade
      size indicate that visual errors, not correction saccades, drive the adaptation
      of saccades.

PMID- 11587899
TI  - fMRI-derived cortical maps for haptic shape, texture, and hardness.
AB  - We used functional magnetic resonance imaging (fMRI) to investigate the neural
      substrates involved in haptic processing of texture, shape, and hardness.
      Subjects performed haptic classification tasks on a set of 27 silicone objects
      having parametrically defined shape, texture, and hardness. The objects were
      ellipsoids of revolution in which the ratio of the long to the short axis was
      varied, producing three different shapes. Three surface textures and three
      hardness levels were used. In three separate experiments, the same subjects
      classified each object along the three levels of one of the object properties
      (shape, texture, or hardness). Texture, shape, and hardness processing led to
      contralateral activation in the postcentral gyrus (PCG). A common region located
      within relatively posterior portions of the PCG was observed during shape and
      texture identification whereas a separate and more anterior region was activated
      during the hardness identification task. The hardness identification task also
      produced bilateral activation within the parietal operculum.

PMID- 11587900
TI  - Temporal evolution of alpha and beta bands during visual spatial attention.
AB  - Event-related potentials (ERPs) are an electrophysiological index of various
      cognitive processes such as attention. However, this kind of analysis does not
      allow observation of differences in the spectral content taking place during a
      sensory, cognitive or motor task. The goal of the present work was to compute the
      temporal dynamics of EEG oscillations using a technique called temporal spectral
      evolution (TSE). The electroencephalogram (EEG) was recorded during the
      presentation of flashed stimuli that were randomly presented to the left or right
      visual field. Subjects were asked to pay attention, alternately in different
      blocks of trials, to the left or to the right to detect an infrequent target. The
      results showed a decrease in the alpha band in a time window of 375-500 ms and an
      increase in the beta band at 500-875 ms after stimulus onset, for both attended
      and unattended stimuli. Statistical analysis showed that the decrease in alpha
      and the increase in beta were more marked during the attentional condition. In
      conclusion, these results demonstrate that the decrease in alpha band and the
      increase in beta band are electrophysiological markers of visual spatial
      attention.

PMID- 11587901
TI  - Electrophysiological evidence of a semantic system commonly accessed by animals
      and tools categories.
AB  - Some theoretical perspectives propose a semantic system in which categories are
      represented in different brain regions. Others assume that distinctions are based
      rather on differences in the demands placed by different categories on shared
      processing systems. In this study semantic categorization processes were
      investigated using the recognition potential (RP), an event-related brain
      response that reflects semantic processing, peaks at around 250 ms after stimulus
      onset and originates in areas subserving perceptual-semantic analyses. Results
      indicate that the RP shows some degree of sensitivity to categorization
      processes, but that categories assumed to differ markedly in their processing
      demands share, to a large extent, a common neural generator. This provides
      support for the non-categorical view on the organization of the semantic system,
      though introducing subtle variations, and suggesting the existence of a semantic
      subsystem specializing in the processing of perceptual-semantic features
      regardless of the semantic category involved.

PMID- 11587902
TI  - Mental stimulation increases circulating CD4-positive T lymphocytes: a
      preliminary study.
AB  - To stimulate the dorsolateral frontal cortex, 12 healthy, adult, human females
      played contract bridge for 1.5 h between initial and final blood sample
      collections. Flow cytometric analyses of samples, performed in triplicate, showed
      a significant increase in CD4-positive T lymphocytes. The dorsolateral frontal
      cortical thickness is significantly and bilaterally reduced in immune-incompetent
      female, nude mice. Thymic transplants reverse the deficient cortical thickness
      and CD4-positive cell numbers.

PMID- 11587903
TI  - Hemispheric asymmetries of visual ERPs in left-handed bilinguals.
AB  - ERPs (N1, P1, N2, P2) obtained from left and right occipital and temporal lobes
      were elicited in 30 left-handed highly proficient bilingual males in response to
      visually presented linguistic stimuli. The absence of statistically significant(P
      = < or =0.05) differences between left and right occipital and temporal lobes in
      all the components of the waveforms obtained, indicates a bilateral pattern of
      lateralization in left-handed males for both their native and foreign language.

PMID- 11587904
TI  - Left superior parietal cortex involvement in writing: integrating fMRI with
      lesion evidence.
AB  - Writing is a uniquely human skill that we utilize nearly everyday. Lesion studies
      in patients with Gerstmann's syndrome have pointed to the parietal cortex as
      being critical for writing. Very little information is, however, available about
      the precise anatomical location of brain regions subserving writing in normal
      healthy individuals. In this study, we used functional magnetic resonance imaging
      (fMRI) to investigate parietal lobe function during writing to dictation.
      Significant clusters of activation were observed in left superior parietal lobe
      (SPL) and the dorsal aspects of the inferior parietal cortex (IPC) bordering the
      SPL. Localized clusters of activation were also observed in the left premotor
      cortex, sensorimotor cortex and supplementary motor area. No activation cluster
      was observed in the right hemisphere. These results clearly indicate that writing
      appears to be primarily organized in the language-dominant hemisphere. Further
      analysis revealed that within the parietal cortex, activation was significantly
      greater in the left SPL, compared to left IPC. Together with lesion studies,
      findings from the present study provide further evidence for the essential role
      of the left SPL in writing. Deficits to the precise left hemisphere parietal
      cortex regions identified in the present study may specifically underlie
      disorders of writing observed in Gerstmann's syndrome and apractic agraphia.

PMID- 11587905
TI  - Variable practice with lenses improves visuo-motor plasticity.
AB  - Novel sensorimotor situations present a unique challenge to an individual's
      adaptive ability. Using the simple and easily measured paradigm of visual-motor
      rearrangement created by the use of visual displacement lenses, we sought to
      determine whether an individual's ability to adapt to visuo-motor discordance
      could be improved through training. Subjects threw small balls at a stationary
      target during a 3-week practice regimen involving repeated exposure to one set of
      lenses in block practice (x 2.0 magnifying lenses), multiple sets of lenses in
      variable practice (x 2.0 magnifying, x 0.5 minifying and up-down reversing
      lenses) or sham lenses. At the end of training, adaptation to a novel visuo-motor
      situation (20-degree right shift lenses) was tested. We found that (1) training
      with variable practice can increase adaptability to a novel visuo-motor
      situation, (2) increased adaptability is retained for at least 1 month and is
      transferable to further novel visuo-motor permutations and (3) variable practice
      improves performance of a simple motor task even in the undisturbed state. These
      results have implications for the design of clinical rehabilitation programs and
      countermeasures to enhance astronaut adaptability, facilitating adaptive
      transitions between gravitational environments.

PMID- 11587906
TI  - House calls?

PMID- 11587907
TI  - Pilot test of an Internet virtual world chat room for rural teen smokers.
AB  - OVERVIEW: This pilot study evaluated the acceptability and efficacy of an
      Internet-based virtual reality "world" for teen smoking cessation. Rural teens at
      six school sites interacted in real-time in the virtual world with a trained
      cessation counselor and other teen smokers over a 2-month period in seven 1-hour
      chat sessions. The cessation counselor used motivational interviewing, a "client
      centered" nonconfrontational approach to behavior change that has shown promise
      with behaviors resistant to change. Smoking behavior and attitudes were assessed
      at baseline, after intervention, and at 1-month follow-up. Significant changes
      were found in quitting, amount smoked, and intentions to quit. Positive trends
      were seen in past-week abstinence rates, quit attempts, and attitudes toward
      quitting.

PMID- 11587908
TI  - Video games and real-life aggression: review of the literature.

PMID- 11587909
TI  - Computer usage and its relationship with adolescent lifestyle in Hong Kong.
AB  - PURPOSE: To determine the patterns of computer usage among adolescents in Hong
      Kong and to examine whether computer usage is associated with less physical
      activity and social support among adolescents. METHODS: A total of 2110 secondary
      school students (52% boys and 48% girls) in Hong Kong completed a set of
      questionnaires to measure their computer usage and lifestyle. Mean age of the
      respondents was 14.16 years (SD = 1.81 years). Computer usage was taped by asking
      the students to indicate how much time (in minutes) they spent on the computer
      each day for doing homework assignments; playing computer games; "surfing" the
      Internet; and communicating with others. The students also provided information
      on their social-physical lifestyle. Student's t-tests and analysis of variance
      were used to examine group differences. Pearson product moment correlations were
      used to explore relationships between computer usage and lifestyle. RESULTS: Boys
      who use computers for doing homework, "surfing" the Internet, and communicating
      with others engage in more social-physical activities than others. Boys who use
      computers to play games tend to be more social-behaviorally inactive. For girls,
      patterns of computer usage are not related to lifestyle. CONCLUSIONS: Computer
      users tended to engage in social-physical activities more frequently and had
      higher social support than nonusers. But among computer users, the amount of time
      spent daily on the computer was not associated with lifestyle. Instead, patterns
      of computer usage are more related to lifestyle and the relationship is moderated
      by gender.

PMID- 11587910
TI  - Early detection of cardiac dysfunction: use of the myocardial performance index
      in patients with anorexia nervosa.
AB  - OVERVIEW: Patients with anorexia nervosa have functional cardiac abnormalities
      secondary to their nutritionally depleted state. These abnormalities include
      decreased left ventricular (LV) mass and varying degrees of LV systolic
      dysfunction. Assessment of LV diastolic function and quantitative assessment of
      right ventricular function are not routinely performed. The myocardial
      performance index (MPI) is a relatively new, simple, quantitative measure of
      global myocardial function. The purpose of this study was to evaluate left and
      right ventricular function in 13 patients with anorexia nervosa with the MPI and
      compare it to more commonly used echocardiographic measures of ventricular
      function.

PMID- 11587911
TI  - Poor adolescent expectant mothers: can we assess their potential for child abuse?
AB  - PURPOSE: To explore the correlates of high scores on the Child Abuse Potential
      Inventory in adolescent expectant mothers. METHODS: Child Abuse Potential scores
      and data on demographics, pregnancy desire, history of maltreatment,
      psychological functioning, and perceived social support were obtained by self
      report and semi-structured interview. The sample consisted of 50 poor single
      adolescents recruited from prenatal clinics during the second half of the
      pregnancy. The relationships among the variables were assessed using Pearson
      product-moment correlation and multiple regression strategies. RESULTS: Higher
      Child Abuse Potential scores were associated with higher maternal psychological
      distress, maternal history of psychiatric diagnosis, and lack of perceived
      support by the father of the baby. Older pregnant teenagers were more likely to
      report childhood history of maltreatment, higher psychological distress, and
      perceived and expected less support by the maternal mother. Expectant mothers who
      were raised by a single parent were more likely to have a history of childhood
      maltreatment, less likely to live with the father of the baby during their
      pregnancy and to expect less support from him. CONCLUSIONS: Child Abuse Potential
      scores, obtained during pregnancy in a sample of poor single adolescents provide
      a marker of maternal prenatal functioning and perceived social support. Further
      studies are warranted to validate prenatal use of the Child Abuse Potential
      Inventory (CAPI), which may help identify populations at particularly high risk
      for child abuse during pregnancy and inform strategies for early preventive
      interventions. Adolescent education on family planning, child rearing, and social
      support programs should address the importance of the fathers' role.

PMID- 11587912
TI  - Relationship between perceived life satisfaction and adolescents' substance
      abuse.
AB  - PURPOSE: To explore the relationship between perceived global life satisfaction
      and selected substance use behaviors among 5032 public high school students.
      METHODS: The 1997 South Carolina Youth Risk Behavior Survey substance abuse and
      life satisfaction variables were used. An adjusted polychotomous logistic
      regression analysis utilizing SAS/SUDAAN, revealed a significant race/gender
      interaction. Subsequent multivariate models were constructed individually for
      four race/gender groups. Adjusted odds ratios and 95% confidence intervals were
      calculated to assess the magnitude of risk for selected substance abuse behaviors
      and their association with reduced global life satisfaction. RESULTS: Cigarette
      smoking, chewing tobacco, marijuana, cocaine, regular alcohol use, binge
      drinking, injection drug, and steroid use were significantly (p < .05) associated
      with reduced life satisfaction for specific race/gender groups (white males;
      black males; white females; and black females). In addition, age (< or = 13
      years) of first alcohol drink, first marijuana use, first cocaine use, and first
      cigarette smoked were also significantly (p < .05) associated with reduced life
      satisfaction. CONCLUSION: Longitudinal studies are needed to determine whether
      dissatisfaction with life is a consequence or determinant of substance abuse
      behavior for adolescents.

PMID- 11587913
TI  - Choosing to remain smoke-free: the experiences of adolescent girls.
AB  - PURPOSE: To develop an understanding of the experiences of nonsmoking girls and
      determine how these girls avoid smoking. METHODS: A grounded theory approach was
      used to direct the discovery of process(es) that nonsmoking females undertake to
      remain nonsmokers. Seventeen nonsmoking females between the ages of 13 and 17
      years were interviewed using open-ended questions designed by the authors. The
      interviews were tape-recorded and then analyzed using the techniques described by
      Strauss and Corbin. RESULTS: The data revealed that the process of remaining a
      nonsmoker is composed of three phases: making sense of smoking, rejecting
      smoking, and declaring oneself to be a nonsmoker. The process of remaining a
      nonsmoker appears to be rooted in developing self-confidence. As girls rejected
      smoking, self-confidence was boosted because they learned that their choice would
      be accepted and their strategies were effective in rejecting smoking.
      CONCLUSIONS: The findings of this study offer new insights into the experiences
      of adolescent nonsmokers. Our assumption that there is a process that underlies
      remaining a nonsmoker was supported. The findings suggest that adolescents use
      several strategies in this process. These strategies are noteworthy because they
      offer those who work in the field of health promotion new insights into ways in
      which they might contribute to increasing the ranks of nonsmokers.

PMID- 11587914
TI  - Korean adolescents' health risk behaviors and their relationships with the
      selected psychological constructs.
AB  - PURPOSE: To explore the negative health behaviors of Korean adolescents, reveal
      factors affecting their negative health behavior, and present a substantial
      correlation model between the negative health behaviors and psychological
      factors. METHODS: A total of 2124 adolescents randomly selected from junior high
      and high schools in Seoul were surveyed. Four Korean-version instruments were
      used to identify the negative health behavior and psychological construct of
      adolescents: Adolescent Health Survey, Health Locus of Control scale, Self-Esteem
      scale, and Self-Efficacy scale. RESULTS: Korean adolescents showed high
      prevalence of smoking, drinking alcohol, bad eating habits, and viewing
      pornography; and very low prevalence, however, of sexual intercourse and illegal
      drug use. In addition to this, the findings revealed that the subdomains in
      adolescents' negative health behavior were statistically correlated with the
      subdimensions of a psychological factor. A correlation model was an adequate fit
      to identify a possible relationship between the negative health behaviors and the
      psychological factors. CONCLUSIONS: This study provides significant and new
      information about the relatively unstudied Korean adolescents and has the
      potential to influence the development of better health education and health
      psychology.

PMID- 11587915
TI  - An integrated hypothesis that considers drusen as biomarkers of immune-mediated
      processes at the RPE-Bruch's membrane interface in aging and age-related macular
      degeneration.
AB  - Age-related macular degeneration (AMD) is a blinding disease that afflicts
      millions of adults in the Western world. Although it has been proposed that a
      threshold event occurs during normal aging which leads to AMD, the sequelae of
      biochemical, cellular, and/or molecular events leading to the development of AMD
      are poorly understood. Although available data provide strong evidence that a
      significant proportion of AMD has a genetic basis, no gene(s) has yet been
      identified that causes a significant proportion of AMD. Moreover, no major
      molecular pathways involved in the etiology of this disease have been
      elucidated.Drusen, pathological deposits that form between the retinal pigmented
      epithelium (RPE) and Bruch's membrane, are significant risk factors for the
      development of AMD. In our view, the development of testable new hypotheses of
      drusen origins has been hindered significantly by the absence of a comprehensive
      profile of their molecular composition. In this review, we describe an integrated
      ultrastructural, histochemical, molecular biological, and biochemical approach to
      identify specific molecular pathways associated with drusen biogenesis. The
      implicit assumption underlying these recent investigations has been that a
      thorough understanding of the composition of drusen and source(s) of drusen
      associated material is likely to provide fresh insight into the pathobiology
      underlying AMD. Significantly, these studies have revealed that proteins
      associated with inflammation and immune-mediated processes are prevalent among
      drusen-associated constituents. Transcripts that encode a number of these
      molecules have been detected in retinal, RPE, and choroidal cells. These data
      have also lead to the observations that dendritic cells, potent antigen
      presenting cells, are intimately associated with drusen development and that
      complement activation is a key pathway that is active both within drusen and
      along the RPE-choroid interface. We propose herein a unifying hypothesis of
      drusen biogenesis that attempts to incorporate a large body of new and previously
      published structural, histochemical, and molecular data pertaining to drusen
      composition and development. This theory is put forth with the acknowledgment
      that numerous AMD genotypes may exist. Thus, only some aspects of the proposed
      hypothesis may be involved in any given AMD genotype. Importantly, this
      hypothesis invokes, for the first time, the potential for a direct role of cell-
      and immune-mediated processes in drusen biogenesis. We acknowledge that the
      proposed hypothesis clearly represents a paradigm shift in our conceptualization
      pertaining to pathways that participate in the development of drusen and age
      related macular degeneration. It is our hope that other investigators will test,
      validate and/or refute various aspects of this hypothesis, and in so doing,
      increase our overall understanding of the biological pathways associated with
      early AMD.

PMID- 11587916
TI  - Recent advances in our understanding of rhodopsin and phototransduction.
AB  - The present models of phototransduction for vertebrates and invertebrates have
      been reviewed and the relative literature updated. The emerging picture for
      vertebrate phototransduction is a result of a better knowledge of its general
      outlines, although some important details such as the role of calcium ions are
      still lacking. The molecular events involved in the rising phase of the
      electrical response have basically been understood, whilst those involved in
      response inactivation and recovery remain to be elucidated. In an overall
      strategy, the phototransduction in invertebrates shares a great deal of
      similarity with that in vertebrates but differs in the underlying molecular
      events. However, a complete picture of phototransduction in invertebrate
      photoreceptors has not yet emerged. The available data on the structure of the
      visual pigment rhodopsin reveal further details on the present model of the
      retinal-binding pocket of the protein and consequently of the "red shift" of the
      absorbance of retinal. The problem of the energy supplied during photoreception,
      in particular, the availability of ATP in the rod outer segment and the presence
      in the disk membranes of a Ca-ATPase are discussed. Finally, recent progress in
      understanding the molecular mechanisms of inherited retinal diseases and relative
      gene identification are summarized.

PMID- 11587917
TI  - Regulation of ocular inflammation--what experimental and human studies have
      taught us.
AB  - Study of models of ocular autoimmunity and of autoimmune uveitis in humans has
      lead to a shift in the perceived nature of immune privilege from one based on
      anatomical isolation of the eye to a more dynamic, active process of immune
      tolerance. Using a variety of available models, the basis for this dynamic
      process of immune regulation is reviewed. The protective role of humoral
      immunity, the co-stimulatory function of B cells in EAU as well as the influence
      of cytokines within the inflammatory cascade are outlined. Modulation of the
      immune response and in particular the possible role of macrophages is explored.
      Within the current paradyme, a major effector cell is the CD4+ lymphocyte. Its
      maturation into a Th1 or Th2 phenotype process appears dependent on a number of
      exogenous factors, which while genetically determined can be manipulated prior to
      disease onset. Activation of CD4+ cells is dependent on presentation of
      immunoreactive peptide fragments. These fragments are well characterized in the
      Lewis rat for S-Ag and interphotoreceptor retinoid binding protein (IRBP).
      Mapping of the immunoreactivity to S-Ag has been recently completed in uveitis
      patients. An overlap with certain determinants identified in experimental models
      has been observed, in at least 2 disease entities. However, the response profile
      is not fixed in time and is subject to determinant spread. Future studies will be
      aimed at identifying with more detail immunologic triggers of inflammation in
      patients, and at better defining the interplay between effector and regulatory
      pathways both in the eye and in the systemic circulation.

PMID- 11587918
TI  - Development of the primate retinal vasculature.
AB  - Human and macaque retinae have similar retinal vascular anatomy. The general
      features of the retinal vascular anatomy of these two primates have much in
      common with more widely studied animal models such as rat and cat. However,
      primates are unique amongst mammals in having a region in temporal retina
      specialized for high visual acuity, which includes the fovea centralis (or
      'fovea'). Several features distinguish the fovea from other parts of the retina,
      including a very high local density of cone photoreceptors, a high density of
      inner retinal cells during development, and an absence of retinal blood vessels.
      The retinal vascular complex comprises a number of cell types, in addition to
      vascular endothelial cells, including pericytes, microglia, astrocytes-none of
      which is intrinsic to the retina. In addition, amacrine-like cells make bouton
      like associations with retinal vessels and may be involved in the autoregulation
      of blood flow. During development endothelial cells 'invade' the retina,
      accompanied by a population of microglial cells; glial fibrillary acidic protein
      (GFAP)-immunoreactive astrocytes are also seen associated with the developing
      vasculature, and are in advance of the vascular front by a few hundred microns.
      Recent findings indicate that astrocytes at the vascular front proliferate in
      response to factors released by endothelial cells, including leukemia inhibitory
      factor. Better understood is the role of GFAP-immunoreactive astrocytes just in
      advance of the developing vessels. These astrocytes are sensitive to hypoxia and
      in response release vascular endothelial growth factor (VEGF) which in turn
      promotes the migration, differentiation and proliferation of vascular endothelial
      cells. This hypoxia/VEGF-mediated process of migration, proliferation and
      differentiation appears common to the retinae of a variety of species, including
      human. However, in human and macaque retina, different mechanisms appear to
      govern the development of the retinal vessels growing along the horizontal
      meridian of the retina towards the central area, which contains the fovea.
      Despite the relatively advanced state of differentiation and maturation of cells
      in the central area compared with the periphery, the growth of retinal vessels
      into the central area has been described as 'retarded', and the incidence of cell
      proliferation associated with these vessels is lower than in peripheral vessels.
      Furthermore, neither retinal vessels nor their accompanying astrocytes grow into
      a circumscribed region which, at a later stage, develops into the foveal
      depression. These observations suggest that molecular markers define the foveal
      region and inhibit cell proliferation and vascular growth at the fovea and,
      perhaps, along the horizontal meridian. The findings also suggest that at the
      fovea, the retina is adapted morphologically to its blood supply, since in the
      vicinity of the fovea, the development of retinal vessels is retarded or
      inhibited. The limitations on vascularization of central retina has implications
      for its vulnerability to degenerative changes, as seen in age-related macular
      degeneration.

PMID- 11587919
TI  - Role of nitric oxide in the control of ocular blood flow.
AB  - In the recent years it has been recognized that nitric oxide is an important
      regulator of ocular blood flow. Nitric oxide is involved in the control of basal
      blood flow in the choroid, optic nerve and the retina. In addition, nitric oxide
      mediates a number of vasodilator responses in ocular vessels to agonists such as
      acetylcholine, bradykinin, histamine, substance P and insulin. Nitric oxide also
      plays a role in hypercapnia-induced vasodilation in the choroid and is a
      modulator of pressure autoregulation in this vascular bed. Abnormalities of the L
      arginine/nitric oxide system have been observed in a variety of ocular diseases
      including glaucoma, diabetic retinopathy and retinopathy of prematurity. This
      makes the L-arginine/nitric oxide pathway an attractive target for therapeutic
      interventions. Additional research is required, particularly in characterizing
      the role of the three nitric oxide synthase isoforms in the control of ocular
      perfusion, to implement this concept into the clinical management of ocular
      diseases.

PMID- 11587923
TI  - Veterinary use and antibiotic resistance.
AB  - Globally, an estimated 50% of all antimicrobials serve veterinary purposes.
      Bacteria that inevitably develop antibiotic resistance in animals comprise food
      borne pathogens, opportunistic pathogens and commensal bacteria. The same
      antibiotic resistance genes and gene transfer mechanisms can be found in the
      microfloras of animals and humans. Direct contact, food and water link animal and
      human habitats. The accumulation of resistant bacteria by the use of antibiotics
      in agriculture and veterinary medicine and the spread of such bacteria via
      agriculture and direct contamination are documented.

PMID- 11587924
TI  - Multidrug resistance in Gram-negative bacteria.
AB  - Broadly specific, so-called multidrug, efflux mechanisms are now known to
      contribute significantly to intrinsic and acquired multidrug resistance in a
      number of Gram-negative bacteria, and the boom in bacterial genomics has
      confirmed the distribution of these systems in all bacteria. This broad
      distribution of multidrug transporters lends a certain credibility to suggestions
      that they play a housekeeping role in the cell, beyond any contributions they may
      make to antimicrobial efflux and resistance. In many instances, these
      transporters are dispensable, arguing against their carrying out essential
      cellular functions; nevertheless, the multiplicity of these broadly specific
      export systems within a given microorganism, often with overlapping substrate
      specificity, may explain the dispensability of individual exporters. Whatever
      their intended function, however, their conservation in so many organisms
      highlights their probable general importance in antimicrobial resistance,
      particularly in Gram-negative bacteria whose outer membranes work synergistically
      with many of these export systems to promote drug exclusion.

PMID- 11587925
TI  - Efflux-mediated drug resistance in Gram-positive bacteria.
AB  - Gram-positive bacteria express numerous membrane transporters that promote the
      efflux of various drugs, including many antibiotics, from the cell to the outer
      medium. Drug transporters can be specific to a particular drug, or can have broad
      specificity, as in so-called multidrug transporters. This broad specificity can
      be a consequence of the hydrophobic nature of transported molecules, as suggested
      by recent structural studies of soluble multidrug-binding proteins. Although the
      functions of drug transporters may involve both the protection of bacteria from
      outside toxins and the transport of natural metabolites, their clinical
      importance lies largely in providing Gram-positive pathogens with resistance to
      macrolides, tetracyclines and fluoroquinolones. A number of agents, discovered in
      recent years, that inhibit drug transporters can potentially be used to overcome
      efflux-associated antibiotic resistance.

PMID- 11587926
TI  - Discovering essential and infection-related genes.
AB  - Transposon-based approaches are very powerful for identification of essential and
      infection-related genes in bacteria, particularly in the context of microbial
      genomics. We describe recent progress in several of these approaches, and their
      underlying principles. The essential gene test (EGT) is a transposon-based
      technique that can rapidly identify a nucleotide sequence from a database as
      essential or dispensable. Also, variations of in vitro transposon mutagenesis
      applications, such as genomic analysis and mapping by in vitro transposition
      (GAMBIT), are described. The development of techniques including PCR-based
      signature-tagged mutagenesis is now used to find essential virulence genes in
      different bacterial hosts. These approaches form the basis for the identification
      of microbial targets in development of novel antimicrobials and vaccines by the
      biotechnology and pharmaceutical industry.

PMID- 11587927
TI  - The role of combichem in antibiotic discovery.
AB  - Combinatorial chemistry (combichem) has had a significant impact on the discovery
      of new antibiotics. Most of the successes have come from the use of small
      libraries to explore a specific pharmacophore. However, large diverse libraries
      are more appropriate when identifying hits by screening specific bacterial or
      fungal targets. Combichem has been used to optimize new azole and oxazolidinone
      leads. An entirely new class of antibiotics, inhibitors of bacterial peptidyl
      deformylase, has been discovered by combining mechanism-based drug design and
      combichem. These compounds are active in vivo. The impact of combichem on
      discovery projects that aim to develop new antibiotics for the treatment of
      infectious diseases is discussed.

PMID- 11587928
TI  - Combinatorial biosynthesis of antimicrobials and other natural products.
AB  - Combinatorial biosynthesis utilizes the enzymes from antibiotic (and other
      natural product) biosynthetic pathways to create novel chemical structures. The
      manipulation of modular polyketide synthases (PKSs) has been the major focus of
      this effort and has led to the production of, for example, several erythromycin
      analogs. Many new tools for manipulating and studying these multifunctional
      enzymes have been developed. These include multiple hosts and expression systems,
      enzymology tools for in vitro study, and ways to engineer pre-PKS and post-PKS
      pathways. The result is more rational and faster methods of engineering new
      compounds for the development of chemotherapeutic agents from natural products.
      The most significant recent advances in combinatorial biosynthesis are outlined.

PMID- 11587929
TI  - New antiretroviral agents: looking beyond protease and reverse transcriptase.
AB  - The clinical utility of intervention in HIV-1 disease has been proven by
      inhibitors targeting reverse transcriptase and protease. However, novel
      approaches including inhibition of viral entry, integration and assembly would
      provide additional options to maintain long-term suppression. The identification
      of specific inhibitors for each of these processes has recently validated these
      approaches as viable alternatives for the development of new agents to treat HIV
      1 infection. The most recent preclinical advances in novel antiretroviral agents
      are reviewed and promising new approaches that target viral processes are
      highlighted.

PMID- 11587930
TI  - Antifungals: what's in the pipeline.
AB  - The therapeutic landscape for mycotic infections is shifting. New generation
      azoles that are active against clinically relevant, drug-resistant fungal
      pathogens have improved bioavailability, half-lives and safety profiles. Acylated
      cyclic peptide inhibitors of beta(1,3)glucan synthesis with origins as fungal
      metabolites provide an alternative and highly-selective mode of action, targeting
      cell-wall biogenesis in important pathogens such as Candida and Aspergillus
      species. The development, in each structural class, of compounds that have
      advanced to late-stage clinical trials is summarized in this review.

PMID- 11587932
TI  - Whole genome plasticity in pathogenic bacteria.
AB  - The exploitation of bacterial genome sequences has so far provided a wealth of
      new general information about the genetic diversity of bacteria, such as that of
      many pathogens. Comparative genomics uncovered many genome variations in closely
      related bacteria and revealed basic principles involved in bacterial
      diversification, improving our knowledge of the evolution of bacterial pathogens.
      A correlation between metabolic versatility and genome size has become evident.
      The degenerated life styles of obligate intracellular pathogens correlate with
      significantly reduced genome sizes, a phenomenon that has been termed "evolution
      by reduction". These mechanisms can permanently alter bacterial genotypes and
      result in adaptation to their environment by genome optimization. In this review,
      we summarize the recent results of genome-wide approaches to studying the genetic
      diversity of pathogenic bacteria that indicate that the acquisition of DNA and
      the loss of genetic information are two important mechanisms that contribute to
      strain-specific differences in genome content.

PMID- 11587933
TI  - The circle is broken: telomere resolution in linear replicons.
AB  - Linear DNA molecules with covalently closed hairpin ends (telomeres) exist in a
      wide variety of organisms. Telomere resolution, a DNA breakage and reunion
      reaction in which replicated telomeres are processed into hairpin ends, is now
      known to be a common theme in poxviruses, Borrelia burgdorferi and Escherichia
      coli phage N15. Candidate proteins that may perform this reaction have recently
      been identified in poxviruses. Moreover, the first purification and definitive
      identification of a telomere resolvase has been reported for phage N15. This
      protein is the prototype for a new class of DNA enzyme that performs a unique
      reaction. Advances in the study of telomere resolution in poxviruses, B.
      burgdorferi and E. coli phage N15 are discussed.

PMID- 11587934
TI  - Integrons: natural tools for bacterial genome evolution.
AB  - Integrons were first identified as the primary mechanism for antibiotic
      resistance gene capture and dissemination among Gram-negative bacteria. More
      recently, their role in genome evolution has been extended with the discovery of
      larger integron structures, the super-integrons, as genuine components of the
      genomes of many species throughout the gamma-proteobacterial radiation. The
      functional platforms of these integrons appear to be sedentary, whereas their
      gene cassette contents are highly variable. Nevertheless, the gene cassettes for
      which an activity has been experimentally demonstrated encode proteins related to
      simple adaptive functions and their recruitment is seen as providing the
      bacterial host with a selective advantage. The widespread occurrence of the
      integron system among Gram-negative bacteria is discussed, with special focus on
      the super-integrons. Some of the adaptive functions encoded by these genes are
      also reviewed, and implications of integron-mediated genome evolution in the
      emergence of novel bacterial species are highlighted.

PMID- 11587935
TI  - Playing Dr Jekyll and Mr Hyde: combined mechanisms of phase variation in
      bacteria.
AB  - Phase variation is the adaptive process by which bacteria undergo frequent and
      reversible phenotypic changes resulting from genetic alterations in specific loci
      of their genomes. This process is crucial for the survival of pathogens and
      commensals in hostile and ever-changing host environments. Despite important
      differences in the molecular mechanisms that mediate and regulate phase
      variation, related strategies have evolved to generate high levels of genetic
      diversity through complex and combinatorial reshuffling of genetic information.
      Recent studies, supported by the emergence of global genomic approaches, have
      revealed that bacterial pathogens often use a combination of different mechanisms
      to vary the expression of a variety of biological functions, providing new
      insights into bacterial adaptation and virulence mechanisms. Recent advances in
      the understanding of the molecular mechanisms of phase variation are reviewed,
      and differences in these mechanisms outlined.

PMID- 11587936
TI  - The rise and fall of mutator bacteria.
AB  - Bacteria with elevated mutation rates are frequently found among natural
      isolates. This is probably because of their ability to generate genetic
      variability, the substrate for natural selection. However, such high mutation
      rates can lead to the loss of vital functions. The evolution of bacterial
      populations may happen through alternating periods of high and low mutation
      rates. The cost and benefits of high mutation rates in the course of bacterial
      adaptive evolution are reviewed.

PMID- 11587938
TI  - The replication-recombination connection: insights from genomics.
AB  - One amazing characteristic of DNA processing enzymes is their breakneck speed.
      However, considering the metabolic traffic on DNA, it is not surprising that
      accidents that interrupt the replication process and require immediate repair
      occur. Recombination is an example of a repair mechanism, and as a result of
      accidents, the arrested or broken fork becomes the recombination substrate.
      Repair proteins are on hand to assist at accident sites, but responses may be
      sensitive to conditions and depend on the organism. Genomics has been used to
      identify genetic clues that indicate the occurrence of accidents and to detect
      sites of recombination. DNA and protein features that may affect replication and
      recombination are examined and discussed.

PMID- 11587937
TI  - Adaptive mutations, mutator DNA polymerases and genetic change strategies of
      pathogens.
AB  - "Adaptive" or "stationary-phase" mutation is a collection of stress responses
      promoting mutations, some of which are advantageous. In 2000 and 2001, in
      Escherichia coli, adaptive gene amplification was documented, and a parallel
      adaptive point-mutation mechanism was linked to the error-prone DNA polymerase,
      DinB (pol IV). We suggest that DinB homologues may contribute to adaptive
      strategies of pathogens, including antigenic variation.

PMID- 11587939
TI  - The relative contributions of recombination and point mutation to the
      diversification of bacterial clones.
AB  - Low levels of recombination in bacterial species have often been inferred from
      the presence of linkage disequilibrium between the alleles at different loci in
      the population. However, significant linkage disequilibrium is inevitable in
      organisms that divide by binary fission, and recombinational replacements must be
      very frequent, compared to point mutation, to dissipate disequilibrium. Recent
      studies using data from multilocus sequence typing indicate that, in many
      species, recombinational replacements contribute more greatly to clonal
      diversification than do point mutations and, in some species, recombination has
      been sufficient to eliminate any phylogenetic signal from gene trees. Recent
      efforts to improve understanding of the extent and impact of homologous
      recombination in the diversification of bacterial clones are discussed.

PMID- 11587940
TI  - Towards elimination of lymphatic filariasis in India.
AB  - The global initiatives to eliminate lymphatic filariasis as a public health
      problem by the year 2020 have generated a great deal of debate in India, the
      largest endemic country. This has led to a shift in the focus from control to
      elimination of the disease. Although the campaign to eliminate filariasis has
      begun, much more needs to be done. Several recent research studies have provided
      an insight into various operational issues and prospects of elimination of
      lymphatic filariasis. In this article, the current scenario, recent research
      results, logistics and the prospects of eliminating lymphatic filariasis in India
      will be discussed.

PMID- 11587941
TI  - Toxoplasmosis: a persisting challenge.
AB  - The sixth biennial International Congress on Toxoplasmosis, organized by Uwe
      Gross (University of Gottingen, Germany), was held on 21-25 May 2001 in Freising,
      Germany. The first meeting of this kind in 1990 was attended by only 26
      investigators and this year there were 115 participants covering various research
      topics including the immunology, epidemiology, cellular and molecular biology of
      Toxoplasma gondii.

PMID- 11587942
TI  - Human giardiasis: genotype-linked differences in clinical symptomatology.

PMID- 11587943
TI  - Skinny rodents, kala-azar and prostaglandin E(2).

PMID- 11587944
TI  - The world of smoke, mirrors and climate change.

PMID- 11587960
TI  - River blindness: a role for parasite retinoid-binding proteins in the generation
      of pathology?
AB  - A new family of fatty acid- and retinoid-binding proteins has recently been
      identified in nematodes. These are apparently nematode specific and have very
      different structures and binding characteristics to their mammalian counterparts.
      Retinoids have important roles in vision, tissue differentiation and repair, and
      can profoundly affect collagen synthesis. Binding proteins released by a parasite
      might therefore play a part in the generation of the skin and eye pathology seen
      in river blindness. They might also be involved in the formation of the
      subcutaneous nodules induced by this parasite.

PMID- 11587961
TI  - Clonal variation of gene expression as a source of phenotypic diversity in
      parasitic protozoa.
AB  - Within a cellular clone, individual cells can express different members of a gene
      family. If the difference in expression is transmitted to daughter cells,
      'phenotypic clones' are formed. Such clonal phenotypic variation has evolved
      independently in phylogenetically distant parasitic protozoa under similar
      selective pressure: the need for phenotypic diversity at several steps of their
      life cycle. Here, I review clonal phenotypic variation processes, outline their
      role in parasite biology and argue that clonal phenotypic variation is
      complementary to sexual reproduction as a source of phenotypic diversity.

PMID- 11587962
TI  - Intracellular protozoan parasites and apoptosis: diverse strategies to modulate
      parasite-host interactions.
AB  - Programmed cell death (apoptosis) is an important regulator of the host's
      response during infection with a variety of intracellular protozoan parasites.
      Parasitic pathogens have evolved diverse strategies to induce or inhibit host
      cell apoptosis, thereby modulating the host's immune response, aiding
      dissemination within the host or facilitating intracellular survival. Here, we
      review the molecular and cell-biological mechanisms of the pathogen-induced
      modulation of host-cell apoptosis and its effects on the parasite-host
      interaction and the pathogenesis of parasitic diseases. We also discuss the
      previously unrecognized phenomenon of apoptotic cell death in (unicellular)
      protozoan parasites and its potential implications.

PMID- 11587963
TI  - The dual role of CTLA-4 in Leishmania infection.
AB  - The role of CTLA-4 in inducing the production of transforming growth factor beta
      (TGF-beta) from T cells during a Leishmania infection has only recently been
      recognized. However, CTLA-4 and TGF-beta affect T helper cells differently,
      depending on the maturation. This review discusses the data obtained from
      different experimental models and demonstrates that CTLA-4 is a target molecule
      for vaccination and therapy against leishmaniasis.

PMID- 11587964
TI  - Aspartyl proteinase genes from apicomplexan parasites: evidence for evolution of
      the gene structure.
AB  - Aspartyl proteinases are a widely distributed family of enzymes. All vertebrate
      aspartyl proteinases share a conserved nine-exon gene structure, but in other
      organisms the structure of aspartyl proteinase genes varies considerably. The
      exon-intron patterns generally reflect phylogeny based on amino acid sequences.
      However, close comparison of these gene structures reveals some striking
      features, such as the conservation of intron positions and intron phases between
      aspartyl proteinases from nematodes and apicomplexans. Here, we discuss the
      implications of gene structure for the possible evolution of the aspartyl
      proteinase family, with particular reference to the plasmepsins of Plasmodium
      falciparum and eimepsin from Eimeria tenella.

PMID- 11587965
TI  - A historic photomicrograph of a parasite (Trichomonas vaginalis).
AB  - Knowing that Alfred Donne was the discoverer of an important human parasite, and
      finding that he was also a pioneer of photomicrography, it occurred to me that
      his parasite might well have become a subject of his photography. It was a simple
      matter to confirm that this was indeed the case. The parasite he discovered was
      Trichomonas vaginalis; and, in collaboration with Foucault, Donne made a
      photomicrograph showing several protozoan parasites lying among vaginal
      epithelial cells. His publication of an engraved image of the photomicrograph in
      1845, was a landmark in the history of photography and microbiology.

PMID- 11587966
TI  - Mining the schistosome DNA sequence database.

PMID- 11587968
TI  - On keeping an eye on the right ventricle in sleep apnea.

PMID- 11587969
TI  - Controlling tuberculosis among foreign born within industrialized countries:
      expensive band-aids.

PMID- 11587970
TI  - The effect of BCG vaccination on tuberculin skin testing. Does it matter?

PMID- 11587971
TI  - Management of acute coronary syndromes.

PMID- 11587972
TI  - Long-acting inhaled beta(2)-agonist therapy in asthma.

PMID- 11587973
TI  - Echocardiographic features of the right heart in sleep-disordered breathing: the
      Framingham Heart Study.
AB  - The effect of sleep-disordered breathing (SDB) on right heart structure and
      function is controversial. Studies of patients referred for evaluation of
      possible sleep apnea have yielded conflicting results, and the impact of SDB on
      the right heart has not been investigated in the general population. We examined
      the echocardiographic features of subjects with SDB at the Framingham Heart Study
      site of the Sleep Heart Health Study. Of 1,001 polysomnography subjects, 90 with
      SDB defined as a respiratory disturbance index (RDI) score > 90th percentile
      (mean RDI = 42) were compared with 90 low-RDI subjects (mean RDI = 5) matched for
      age, sex, and body mass index. Right heart measurements, made without knowledge
      of clinical status, were compared between groups. The majority of the subjects
      were male (74%). After multivariable adjustment, right ventricle (RV) wall
      thickness was significantly greater (p = 0.005) in subjects with SDB (0.78 +/-
      0.02 cm) than in the low-RDI subjects (0.68 +/- 0.02 cm). Right atrial
      dimensions, RV dimensions, and RV systolic function were not found to be
      significantly different between subjects with SDB and the low-RDI subjects. We
      conclude that in this community-based study of SDB and right heart
      echocardiographic features, RV wall thickness was increased in subjects with SDB.
      Whether the RV hypertrophy observed in persons with SDB is associated with
      increased morbidity and mortality remains unknown.

PMID- 11587974
TI  - Effectiveness of continuous positive airway pressure in mild sleep apnea-hypopnea
      syndrome.
AB  - The aim of this trial was to evaluate the effectiveness of continuous positive
      airway pressure (CPAP) in patients with mild sleep apnea- hypopnea syndrome
      (SAHS). One hundred forty-two consecutive patients with mild SAHS (apnea-hypopnea
      index 10-30, without severe sleepiness) were randomly assigned to receive
      conservative treatment (CT)-sleep hygiene and weight loss-(65 patients) or CT
      plus CPAP (77 patients), and 125 patients (86% males, age: 54 +/- 9 yr, BMI: 29
      +/- 4 kg/m(2), AHI: 20 +/- 6, ESS: 12 +/- 4) completed the follow-up. The
      following outcomes were assessed at inclusion and after 3 and 6 mo of treatment:
      sleepiness (Epworth scale, multiple sleep latency test [MSLT]), other symptoms
      related to SAHS, cognitive function, and perceived health status (Functional
      Outcomes of Sleep Questionnaire [FOSQ], Nottingham Health profile). The relief of
      SAHS-related clinical symptoms was significantly greater in the CPAP group than
      in the CT group; the Epworth scale and FOSQ also showed more improvement in the
      CPAP group but did not reach significance. There were no significant differences
      in the other tests performed probably because the baseline values were normal.
      CPAP compliance was 4.8 +/- 2.2 h and treatment continuation was accepted by 62%
      of the patients at the end of the study. These results suggest that CPAP can be
      considered in treating patients with mild SAHS on the basis of an improvement in
      symptoms.

PMID- 11587975
TI  - Characterization of obstructive nonapneic respiratory events in moderate sleep
      apnea syndrome.
AB  - Obstructive nonapneic respiratory events (ONAREs, i.e., obstructive hypopneas
      [OHs] and respiratory effort related arousals [RERAs]) are clinically important
      as producing sleep fragmentation but are much more difficult to detect and
      classify than obstructive apneas. We characterized 1,061 ONAREs in 15 unselected
      patients with moderate sleep apnea-hypopnea syndrome (OSAHS) according to the
      1999 American Academy of Sleep Medicine (AASM) Task Force recommendations
      concerning accurate skills for respiratory measurements (i.e., pneumotachograph
      and esophageal pressure [Pes]) and definitions of respiratory events. OHs were
      defined as > or = 50% decrease in flow or < 50% but > or = 30% decrease in flow
      associated with either a desaturation of > or = 3% or a cortical arousal. RERAs
      corresponded to a less than 30% decrease in flow associated with an arousal. OHs
      represented a large majority of the events (79.9%, n = 848). Among the events
      demonstrating a 30 to 50% reduction in flow (n = 392), the occurrence of a
      cortical arousal permitted the classification of 246 events as OHs (62.8%). RERAs
      represented only 5.3% of the events. Finally 14.8% of the events were classified
      as indeterminate owing to a < 50% and > or = 30% airflow decrease without arousal
      or desaturation or an airflow decrease less than 30% without arousal. The same
      level of DeltaPes was observed at the end of OHs and RERAs (21.9 +/- 5.5 versus
      18.9 +/- 5.7 cm H(2)O respectively [NS]) whereas the reduction in flow was as
      expected, higher for OH (57.9 +/- 10.7 versus 21.3 +/- 4.9%). In a population of
      moderate OSAHS, OH represented the dominant type of ONAREs when RERAs should be
      considered as specific but relatively rare respiratory events. The occurrence and
      the recognition of a microarousal represented the key associated factor for
      classifying respiratory events as hypopneas. The high rate (15%) of unclassified
      events demonstrated some limitations in the AASM Task Force recommendations for
      definitions of respiratory events. Similar levels of DeltaPes found at the end of
      RERAs and OHs, although the reduction in flow was higher for OHs, suggest that
      different levels of collapsibility can exist throughout the night in a given
      patient.

PMID- 11587976
TI  - Genetic factors in self-reported snoring and excessive daytime sleepiness: a twin
      study.
AB  - Subjects in this study included 1,560 intact male-male twin pairs (818
      monozygotic [MZ], 742 dizygotic [DZ]) of mean age (+/- SD) 74.2 +/- 2.8 yr. The
      Epworth Sleepiness Scale (ESS) was used to assess daytime sleepiness and
      standardized questionnaires assessed snoring. Multivariate genetic model fitting
      was used to estimate the contribution of genetic and nongenetic (environmental)
      influences to the variation and covariation of obesity with snoring and daytime
      sleepiness. In this sample, 26% were habitual snorers, 18% reported excessive
      daytime sleepiness (ESS > or = 11), and 29% were obese (body mass index [BMI] >
      or = 28). By using structural equation modeling, we estimated that genetic
      factors accounted for 64% of the variance in obesity, 40% of the variance in
      daytime sleepiness, and 23% of the variability in self-reports of snoring. We
      found a significant genetic correlation between obesity and snoring and between
      obesity and excessive daytime sleepiness (EDS), although for the most part the
      genetic variance in snoring and sleepiness was nonoverlapping with the genetic
      variance for obesity. We conclude from these data that self-reported symptoms of
      snoring and daytime sleepiness in older men have a genetic basis that is largely
      independent of genes associated with obesity.

PMID- 11587977
TI  - Tuberculosis in the foreign-born population of Tarrant county, Texas by
      immigration status.
AB  - The epidemiology of tuberculosis is changing in the United States as a result of
      immigration, yet the extent to which different classes of immigrants contribute
      to overall morbidity is unknown. Tuberculosis in nonimmigrant visitors is of
      particular interest as they are currently exempt from screening requirements. We
      conducted a prospective survey of all culture-positive tuberculosis patients in
      Tarrant County, Texas from 1/98 to 12/00. Immigration status of foreign-born
      patients was classified as permanent residents, undocumented, or nonimmigrant
      visitors. Of 274 eligible participants, 114 (42%) were foreign-born; of these, 67
      (59%) were permanent residents, 28 (25%) were undocumented, and 19 (17%) were
      nonimmigrant visitors. Among the foreign-born, we observed significant
      differences by immigration status in multidrug resistance (p = 0.02), human
      immunodeficiency virus (HIV) infection (p = 0.0007), and hospitalization (p =
      0.03 for ever/never, 0.01 for duration). Compared with other immigrants, more
      nonimmigrant visitors were multi-drug-resistant (16 % versus 11% of undocumented
      residents and 1% of permanent residents), were HIV-positive (32% versus 0% of
      undocumented and 5% of permanent residents), were hospitalized (47% versus 36% of
      undocumented and 19% of permanent residents), and had lengthy hospitalizations
      (median [midspread] days = 87 [25 to 153] versus 8.5 [4 to 28] for undocumented
      and 10 [7 to 24 d] for permanent residents). We found nonimmigrant visitors to be
      an important source of tuberculosis morbidity in Tarrant County. Further studies
      in other regions of the U.S. are needed to determine if screening and treatment
      recommendations of persons who spend extended periods in the U.S. should be
      raised to the standards set for permanent residents.

PMID- 11587978
TI  - Interpretation of the tuberculin skin test in Mycobacterium bovis BCG-vaccinated
      Singaporean schoolchildren.
AB  - Tuberculin skin test (TST) interpretation in Singapore is confounded by universal
      BCG vaccination at birth and by a revaccination policy for schoolchildren who are
      tuberculin nonreactors (TST < 10 mm, using 1 TU PPD RT 23) at 12 or 16 yr old,
      with not more than two BCG vaccinations given to any child. School health records
      for birth cohorts 1978 to 1984 indicate that 82.8% were revaccinated at age 12
      yr. By collation with the national database of tuberculosis (TB) notifications,
      we examined the risk of TB disease in these cohorts for the 4 yr subsequent to
      TST reading at ages 12 and 16 yr respectively, in intervals of 0-4, 5-9, 10-14,
      15-17, and >/= 18 mm. Receiver-operating curves (ROCs) were constructed to
      ascertain the optimum TST cutoffs in screening for the likelihood of development
      of TB disease. A cutoff of 10 mm performed best for the group tested at age 12
      yr, whereas 16 mm was found to be optimum in those tested at age 16 yr (> 80% of
      whom were BCG revaccinated 4 yr earlier). We have extrapolated these findings to
      the screening of contacts, and utilized these cutoff points to guide the
      treatment of latent TB infection in this high-risk group.

PMID- 11587979
TI  - Repeat tuberculin testing in BCG-vaccinated subjects in the United Kingdom. The
      booster effect varies with the time of reading.
AB  - The booster effect varies between populations, but has not been studied in the
      UK. The aim of this study was to investigate the effect of repeat tuberculin
      tests at 1 wk in BCG-vaccinated healthy subjects (all hospital employees) in the
      UK; we have assessed whether a booster effect is present 48 and 72 h after
      injection. Twenty-six subjects received two tuberculin tests (both 10 units)
      administered by the Mantoux technique-Tests 1 and 2. At Test 2 there was a
      significant increase in induration at 48 h (mean, 7.8 mm; p < 0.001), no
      difference at 72 h (mean, 0.2 mm; p = 0.93), and a reduction at 96 h (mean, -4.2
      mm; p = 0.02). There were more positive results (> 15 mm induration) at Test 2
      compared with Test 1 at 48 h (19 vs. 9, respectively; p = 0.002), but similar
      numbers at 72 h (11 vs. 10, respectively). These results show that repeat
      tuberculin testing in this BCG-vaccinated population caused a booster effect that
      varied with the time of measurement and was maximal at 48 h.

PMID- 11587980
TI  - Comparison of the forced oscillation technique and the interrupter technique for
      assessing airway obstruction and its reversibility in children.
AB  - The forced oscillation technique (FOT) and interrupter technique are particularly
      attractive for pediatric use as they require only passive cooperation from the
      patient. We compared the sensitivity and specificity of these methods for
      detecting airway obstruction and its reversibility in 118 children (3-16 yr) with
      asthma or chronic nocturnal cough. FOT (R(0) and R(16)) and interruption (Rint)
      parameters were measured at baseline and after bronchodilator inhalation (n =
      94). Rint was significantly lower than R(0), especially in children with high
      baseline values. Baseline parameters were normalized for height and weight
      [R(SD)]. In children able to perform forced expiratory maneuvers (n = 93), the
      best discrimination between those with baseline FEV(1) < 80% or > or = 80% of
      predicted values was obtained with R(0)(SD). At a specificity of 80%, R(0)(SD)
      yielded 66% sensitivity, whereas Rint(SD) yielded only 33% sensitivity.
      Similarly, postbronchodilator changes in R(0)(SD) [DeltaR(0)(SD)] yielded the
      best discrimination between children with and without significant reversibility
      in FEV(1). At a specificity of 80%, DeltaR(0)(SD) yielded 67% sensitivity and
      DeltaRint(SD) yielded 58% sensitivity. In children unable to perform forced
      expiratory maneuvers (n = 25), FOT, contrary to the interrupter technique,
      clearly identified a subgroup of young children with high resistance values at
      baseline, which returned to normal after bronchodilation. We conclude that, in
      asthmatic children over 3 yr old, FOT measurements provide a more reliable
      evaluation of bronchial obstruction and its reversibility compared with the
      interrupter technique, especially in young children with high baseline values.

PMID- 11587981
TI  - Exposure-response relationship between paternal smoking and children's pulmonary
      function.
AB  - We conducted a cross-sectional study to investigate paternal smoking and
      children's pulmonary function in rural communities of Anqing, China. Our analysis
      included 1,718 children 8 to 15 yr of age whose mothers were never-smokers.
      Multiple linear regression models were used to estimate the effect of paternal
      smoking on children's pulmonary function, with adjustment for children's age,
      sex, weight, height, square of height, asthma, and father's education. When
      compared with children of never-smoking fathers, children of smoking fathers had
      small, but detectable deficits in FEV(1) (-36 ml, SE = 20) and FVC (-37 ml, SE =
      22). When children of smoking fathers were subdivided into two subgroups, father
      smoked < 30 cigarettes/day and >/= 30 cigarettes/day, we found that children
      whose fathers smoked >/= 30 cigarettes/day had the largest deficits in both
      FEV(1) (-79 ml, SE = 30) and FVC (-71 ml, SE = 34). This monotonic exposure
      response relationship remained in all strata when we further stratified our
      analysis by children's sex and asthma status. Our data also suggested that the
      relationship was greatest among nonasthmatic girls, although neither sex nor
      asthma interaction terms were statistically significant. We conclude that there
      is a monotonic exposure-response relationship between paternal smoking and
      decline of pulmonary function in children in this rural Chinese population.

PMID- 11587982
TI  - Airway eosinophilia is associated with wheeze but is uncommon in children with
      persistent cough and frequent chest colds.
AB  - The role of eosinophilic airway inflammation in the variant asthma syndromes of
      cough and chest colds is not well defined. We tested the hypothesis that children
      with persistent cough and chest colds have increased sputum eosinophils, similar
      to those with wheeze. The parents of 390 primary school children completed a
      symptoms questionnaire. Children with wheeze (n = 28), cough (n = 12), recurrent
      chest colds (n = 17), and no symptoms (control subjects, n = 26), underwent
      allergy skin prick tests, spirometry, hypertonic saline inhalation challenge, and
      sputum induction, and then completed a peak expiratory flow (PEF) and symptoms
      diary over a 2-mo period. Children with wheeze had significantly reduced PEF (p =
      0.001) and higher sputum eosinophils when compared with the cough, chest cold,
      and control groups (3.1% versus 0.5%, 0%, 0%; p = 0.03). The prevalence of
      eosinophilic bronchitis (sputum eosinophils > 2.5%) was 45% in the wheeze group,
      which was significantly higher than the control group (9.35%, p = 0.04).
      Eosinophilic bronchitis was present in two children with cough (20%) and two with
      chest colds (15%, p > 0.05 versus control). In these groups, eosinophilic
      bronchitis was not associated with airway hyperresponsiveness (AHR) to hypertonic
      saline (p > 0.05). Children with cough and chest colds reported greater exposure
      to environmental tobacco smoke. In conclusion, this community-based survey of
      children with chronic respiratory symptoms has shown that wheeze is a good
      discriminator for the presence of eosinophilic bronchitis, and that persistent
      cough and recurrent chest colds without wheeze should not be considered a variant
      of asthma. Eosinophilic bronchitis did occur in a significant minority of these
      "variant asthma" syndromes.

PMID- 11587983
TI  - Dose and time response after intraamniotic endotoxin in preterm lambs.
AB  - Intraamniotic endotoxin causes chorioamnionitis, which is followed by improved
      fetal lung function after 4 d in fetal sheep. We evaluated 0.1 mg, 1 mg, 4 mg,
      and 10 mg endotoxin for inflammation and lung maturation effects after 7 d. Four
      and 10 mg endotoxin caused similar lung maturation and inflammation in the lung
      and chorioamnion. The number of neutrophils in cord blood and the inflammatory
      cells in alveolar lavage and fetal lung tissue increased in a dose-dependent
      manner. Lower endotoxin doses induced indicators of chorioamnionitis, lung and
      systemic inflammation without inducing lung maturation. Therefore, some degree of
      inflammation can occur without subsequent lung maturation. The inflammatory
      changes caused by 4 mg endotoxin were assessed after 5 h, 24 h, 72 h, and 7 d to
      discern local versus systemic inflammation after intraamniotic endotoxin. At 5 h
      active inflammatory cells were in the airways producing hydrogen peroxide, and
      interleukin-6 and -8 were increased in the cord blood indicating both lung and
      systemic responses. Cells recruited into the amniotic fluid produced
      proinflammatory cytokine mRNA for 7 d with no cytokine mRNA in chorioamnion,
      lung, or spleen after 72 h. The cells in the amniotic fluid may be a source of
      prolonged fetal exposure to proinflammatory cytokines.

PMID- 11587984
TI  - Prenatal nicotine exposure alters pulmonary function in newborn rhesus monkeys.
AB  - Epidemiological studies have shown that offspring of women who smoke during
      pregnancy have abnormal lung function and associated higher incidences of lower
      respiratory disorders. The recent identification of nicotinic acetylcholine
      receptors (nAChR) in fetal lung suggests that the direct interaction between
      nicotine and nAChR in fetal lung may underlie the postnatal pulmonary
      abnormalities seen in such infants. This hypothesis was tested in monkeys to
      determine if maternal nicotine exposure would produce changes in lung mechanics
      in newborn monkeys similar to those observed in human infants whose mothers
      smoked during pregnancy. Timed pregnant rhesus monkeys were infused with either
      nicotine (1.5 mg/kg/d, n = 7) or saline (n = 7) using subcutaneous osmotic pumps
      from Day 26 to 160 of gestation. On Day 160 of pregnancy (term = 165 d), fetuses
      were delivered by C-section, and the following day were subjected to pulmonary
      function testing. After testing, animals were sacrificed, and lungs weighed and
      fixed. Lung weight and fixed lung volume decreased (16% and 14%, respectively)
      significantly following in utero nicotine exposure. Peak tidal expiratory flow,
      FEV(0.2), mean mid-expiratory flow, forced expiratory volume at peak expiratory
      flow (FEV(PEF)), and FEV(PEF)/FVC% were significantly lower in newborns exposed
      to nicotine during gestation. Absolute and specific pulmonary resistance
      increased significantly whereas absolute and specific dynamic compliance remained
      unchanged in prenatally nicotine-treated pups. These changes in pulmonary
      function are strikingly similar to the changes observed in offspring of human
      smokers. This suggests that the interaction of nicotine with nAChR in developing
      lung is responsible for the altered pulmonary mechanics observed in human infants
      whose mothers smoked during pregnancy.

PMID- 11587985
TI  - Prenatal exposure, maternal sensitization, and sensitization in utero to indoor
      allergens in an inner-city cohort.
AB  - Primary sensitization to antigens may occur prenatally. We hypothesized that high
      prenatal exposure to indoor antigens increases the risk for sensitization in
      newborns in New York City populations with increased risk for asthma. We also
      investigated whether maternal sensitization is required for in utero
      sensitization to occur. One hundred sixty-seven pregnant African American or
      Dominican women residing in northern Manhattan were recruited and antigen was
      measured from home dust. After delivery, newborn cord and maternal blood were
      assayed for IgE and mononuclear cell proliferation and cytokine production in
      response to antigen. Cockroach, mouse, but not dust mite antigens, were commonly
      elevated in the kitchens and pregnant mothers' beds. Increased mononuclear cell
      proliferation occurred in 54% of newborns in response to cockroach, 25% in
      response to dust mite Dermatophagoides pteronyssinus, 40% in response to dust
      mite D. farinae, and 34% in response to mouse protein extracts. Antigen-induced
      mononuclear cell proliferation occurred in cord blood even in the absence of
      antigen-induced mononuclear cell proliferation in the mother. Proliferation in
      response to antigens did not correlate with IgE levels, but proliferation in
      response to dust mite extracts correlated with interluekin-5 (IL-5) production in
      cord blood. These results suggest that (1) high prenatal exposures to cockroach
      and mouse antigens are prevalent; (2) in utero sensitization to multiple indoor
      antigens is common, occurs to a different degree than maternal sensitization, and
      may involve IL-5 upregulation.

PMID- 11587986
TI  - Risk factors for hospitalization for a chronic obstructive pulmonary disease
      exacerbation. EFRAM study.
AB  - Although exacerbation of chronic obstructive pulmonary disease (COPD) is
      important in terms of health and costs, there is little information about which
      are the risk factors. We estimated the association between modifiable and
      nonmodifiable potential risk factors of exacerbation and the admission for a COPD
      exacerbation, using a case-control approach. Cases were recruited among
      admissions for COPD exacerbation during 1 yr in four tertiary hospitals of the
      Barcelona area. Control subjects were recruited from hospital's register of
      discharges, having coincided with the referent case in a previous COPD admission
      but being clinically stable when the referent case was hospitalized. All patients
      completed a questionnaire and performed spirometry, blood gases, and physical
      examination. Information about potential risk factors was collected, including
      variables related to clinical status, characteristics of medical care, medical
      prescriptions, adherence to medication, lifestyle, quality of life, and social
      support. A total of 86 cases and 86 control subjects were included, mean age 69
      yr, mean FEV(1) 39% of predicted. Multivariate logistic regression showed the
      following risk (or protective) factors of COPD hospitalization: three or more
      COPD admissions in the previous year (odds ratio [OR] 6.21, p = 0.008); FEV(1)
      (OR 0.96 per percentual unit, p < 0.0005); underprescription of long-term oxygen
      therapy (LTOT) (OR 22.64, p = 0.007); and current smoking (OR 0.30, p = 0.022).
      Among a wide range of potential risk factors we have found that only previous
      admissions, lower FEV(1), and underprescription of LTOT are independently
      associated with a higher risk of admission for a COPD exacerbation.

PMID- 11587987
TI  - Elevated plasma fibrinogen associated with reduced pulmonary function and
      increased risk of chronic obstructive pulmonary disease.
AB  - We tested whether increased concentrations of the acute-phase reactant fibrinogen
      correlate with pulmonary function and rate of chronic obstructive pulmonary
      disease (COPD) hospitalization. We measured plasma fibrinogen and forced
      expiratory volume in 1 s (FEV(1)), and assessed prospectively COPD
      hospitalizations in 8,955 adults from the Danish general population. Smokers with
      plasma fibrinogen in the upper and middle tertile (> 3.3 and 2.7-3.3 g/L) had 7%
      (95% confidence interval [CI]: 5-8%) and 2% (0-3%) lower percentage predicted
      FEV(1) than smokers with fibrinogen in the lower tertile (< 2.7 g/L). The
      equivalent decreases in nonsmokers were 6% (4-7%) and 0% (-1-2%), respectively.
      Individuals with plasma fibrinogen in the upper and middle tertile had COPD
      hospitalization rates of 93 and 60 compared with 52 per 10,000 person-years in
      individuals with fibrinogen in the lower tertile (log-rank: p < 0.001 and p =
      0.31). After adjusting for age, body mass index, sex, pack-years, and recent
      respiratory infections, relative risks for COPD hospitalization were 1.7 (95% CI:
      1.1-2.6) and 1.4 (0.9-2.1) in individuals with fibrinogen in the upper and middle
      versus lower tertile. In conclusion, elevated plasma fibrinogen was associated
      with reduced FEV(1) and increased risk of COPD. This could not be explained by
      smoking alone.

PMID- 11587988
TI  - Exhaled nitric oxide and hydrogen peroxide in patients with chronic obstructive
      pulmonary disease: effects of inhaled beclomethasone.
AB  - There is controversy about the role of inhaled corticosteroids in chronic
      obstructive pulmonary disease (COPD). Although they appear to have little impact
      on airways obstruction or its progression, their use may reduce the frequency
      and/or severity of exacerbations in a subset of patients. We undertook the
      following study to determine the impact of inhaled corticosteroid on two
      noninvasive markers of airways inflammation. We assigned 20 stable nonsmoking
      patients with COPD in random, double-blind crossover fashion to two 2-wk
      treatment periods with inhaled beclomethasone 500 microg twice daily or matching
      placebo, followed by a 2-wk washout period. We measured exhaled nitric oxide
      (ENO), breath condensate H(2)O(2), and flow volume spirometry at weekly
      intervals. Median baseline ENO was 26.2 (19.3 to 54.8) ppb and fell significantly
      following 1 and 2 wk of beclomethasone (-10.6 ppb, p = 0.002, and -6.3 ppb, p =
      0.013, respectively) but was unchanged by placebo inhalation. Breath condensate
      H(2)O(2) levels did not change significantly with inhaled beclomethasone or
      placebo. Although there were no significant changes in FEV(1) with BDP therapy,
      there was a moderate inverse correlation between changes in ENO and changes in
      FEV(1) (r -0.50). We conclude that inhaled beclomethasone reduces ENO levels in
      stable nonsmoking patients with COPD, a finding compatible with an
      antiinflammatory mechanism of action.

PMID- 11587989
TI  - Interleukin-4 and its alternatively spliced variant (IL-4delta2) in patients with
      atopic asthma.
AB  - The interleukin-4 (IL-4) splice variant (IL-4delta2) is known to antagonize many
      biological activities of IL-4, and this challenges our understanding of the role
      of IL-4 in asthma. Studies that have used nonspecific antibodies, probes, and/or
      primers to quantify IL-4 in clinical samples would not have distinguished the
      expression of IL-4 from IL-4delta2. This is the first study to examine patients
      with chronic asthma and atopy for IL-4delta2 mRNA in their peripheral blood
      mononuclear cells without antigen stimulation, using a quantitative nested
      reverse-transcription polymerase chain reaction (RT-PCR) protocol. The median IL
      4 mRNA copy number in cells from the patients with asthma was 2.8 logs higher
      than in a comparator group of patients with tuberculosis (p = 0.0005) and 4.5
      logs higher (p = 0.0004) than in healthy control subjects. In contrast, IL
      4delta2 expression in cells from patients with asthma was similar to that seen in
      cells from patients with tuberculosis. Hence, the median ratio of IL-4 to IL
      4delta2 was 500-fold higher in the patients with asthma when compared with either
      patients with tuberculosis or healthy control subjects. The relative expression
      of IL-4 and IL-4delta2 may be a reason for the functional diversity of Th2 cells
      in different clinical conditions, and a hitherto unexplored mechanism for the
      pulmonary pathology in patients with atopic asthma.

PMID- 11587990
TI  - In vitro performance characteristics of high-frequency oscillatory ventilators.
AB  - This study aimed to examine the performance characteristics of four high
      frequency oscillatory-type ventilators, using an in vitro model of the intubated
      neonatal respiratory system. Each ventilator was examined across its operative
      range of settings and at varying model lung compliance (C) and resistance. The
      oscillatory pressure waveform was measured at the airway opening (Pao). Tidal
      volume (VT) and flow were determined from pressure changes within the model lung
      (DeltaPA). The spectral content of the Pao waveform differed between ventilators.
      The maximum ventilator VT ranged from 3.7 to 11.1 ml at 15 Hz and a mean airway
      pressure (Paw) of 12 cm H(2)O to oscillate a model lung (C = 0.4 ml/cm H(2)O)
      through a 3.0-mm internal diameter (i.d.) endotracheal tube (ETT). A small drop
      in C was associated with a decrease in VT and marked increase in DeltaPA from 0.1
      to 0.8 ml/cm H(2)O. The influence of C on VT and DeltaPA and the pressure cost of
      ventilation (DeltaPA/f.VT(2)) was dependent on the oscillatory frequency, ETT
      inner diameter, and the specific ventilator used. Substantive differences exist
      between oscillatory ventilators that need to be considered in their clinical
      application. The rapid establishment of optimal lung volume and oscillatory
      frequency is important in minimizing barotrauma during high-frequency oscillatory
      ventilation.

PMID- 11587991
TI  - Idiopathic pulmonary fibrosis: relationship between histopathologic features and
      mortality.
AB  - It is hypothesized that the extent and severity of fibrosis and cellularity found
      on lung biopsy determine the prognosis and response to therapy in idiopathic
      pulmonary fibrosis (IPF). The objective of this study was to determine which
      histopathologic features predict survival in IPF. We prospectively studied 87
      patients with usual interstitial pneumonia (UIP) confirmed by surgical lung
      biopsy. Four pathologists independently graded the extent and severity of
      specific histopathologic features. We used Cox proportional-hazards models to
      assess the effect of histopathologic patterns on patients' survival. The effects
      of age, sex, and smoking were also included in the analysis. Sixty-three patients
      died during the 17-yr study period. Survival was longer in subjects with lesser
      degrees of granulation/connective tissue deposition (fibroblastic foci). The
      degree of alveolar space cellularity, alveolar wall fibrosis, and cellularity did
      not affect survival. A history of cigarette smoking, the level of dyspnea, and
      the degree of lung stiffness at presentation were also shown to be independent
      factors predicting survival. The extent of fibroblastic foci present on lung
      biopsy predicts survival in IPF. These findings support the hypothesis that the
      critical pathway to end-stage fibrosis is not "alveolitis" but rather the ongoing
      epithelial damage and repair process associated with persistent fibroblastic
      proliferation. Controlling these processes, rather than stopping inflammation,
      appears most important in preventing progressive disease and the fatal outcome
      common in IPF.

PMID- 11587992
TI  - Diagnosis of pulmonary embolism in patients with proximal deep vein thrombosis:
      specificity of symptoms and perfusion defects at baseline and during
      anticoagulant therapy.
AB  - To determine the specificity of pulmonary embolism (PE) symptoms and lung scan
      perfusion defects in patients with deep vein thrombosis (DVT), we analyzed data
      on 400 patients with phlebography-proven proximal DVT included in a prospective
      trial. As the incidence of PE during anticoagulant therapy was the main outcome
      measure of the trial, all patients underwent lung scanning and/or pulmonary
      angiography within 48 h of inclusion, and then whenever PE was suspected.
      Angiography was recommended in patients with nondiagnostic lung scan. At
      baseline, the presence or absence of PE could be ascertained in 350 patients
      (87.5%), and 197 (56%) had PE. Sensitivity and specificity of symptoms for PE
      were 74 and 67%, respectively. Among 37 patients with symptoms and nondiagnostic
      lung scan, only 8 (22%) had PE at angiography. During anticoagulant therapy (3
      mo), there were 29 events suspicious for PE, mostly (53%) within 2 wk of
      inclusion. Repeated perfusion studies with comparison to baseline tests excluded
      PE in 21 cases. Cumulated 3-mo risks of suspected and confirmed on-treatment PE
      were 6.8% (95% CI, 5.4- 8.2%) and 2.0% (95% CI, 0.6-3.4%) respectively. Even in
      patients with known proximal DVT, PE symptoms are unspecific and careful imaging
      studies are needed for diagnosis, both at baseline and during anticoagulant
      therapy.

PMID- 11587993
TI  - Increased lipid peroxidation in patients with pulmonary hypertension.
AB  - Isoprostanes are chemically stable lipid peroxidation products of arachidonic
      acid, the quantification of which provides a novel approach to the assessment of
      oxidative stress in vivo. The main objective of this study was to quantify the
      urinary levels of isoprostaglandin F(2alpha) type III (iPF(2alpha)-III), an F(2)
      isoprostane, in patients with pulmonary hypertension (PHT) in comparison with
      healthy controls. The secondary objective was to test whether baseline
      iPF(2alpha)-III levels correlate to the reversibility of pulmonary hypertension
      in response to inhaled NO challenge. Urinary iPF(2alpha)-III levels were measured
      by gas chromatography-mass spectrometry in 25 patients with PHT, 14 of whom were
      investigated for response to inhaled NO challenge. Urinary iPF(2alpha)-III levels
      in PHT patients (225 +/- 27 pmol/mmol creatinine) were 2.3 times as high as in
      controls (97 +/- 7 pmol/mmol creatinine, p < 0.001). The mean pulmonary arterial
      pressure variation and the pulmonary vascular resistance variation in response to
      inhaled NO were correlated to basal iPF(2alpha)-III levels. This study shows that
      oxidative stress is increased in patients with pulmonary hypertension.
      Furthermore, iPF(2alpha)-III levels inversely correlate to pulmonary
      vasoreactivity. These observations are consistent with the hypothesis that free
      radical generation is involved in PHT pathogenesis.

PMID- 11587994
TI  - Passive smoke inhalation decreases exhaled nitric oxide in normal subjects.
AB  - Environmental tobacco smoke (ETS) exposure is one of the commonest pollutants in
      modern society. Despite documented clinical adverse effects of ETS on the lungs,
      objective methods of assessing airway damage have been lacking. Exhaled nitric
      oxide (eNO) is a rapid, sensitive method of assessing airway inflammation, and
      could be useful in this regard. Active smoking decreases eNO in normal subjects
      and eNO levels are low in habitual smokers, but the effect of ETS exposure on eNO
      has not previously been examined. In a single-blinded, placebo-controlled cross
      over study, we examined the effect of ETS, sham and active smoke inhalation on
      eNO in non-smoking normal volunteers. Subjects were exposed to smoke over a
      period of 1 hour in a separately ventilated chamber, and eNO was measured at
      baseline, 15, 30, 45 and 60 minutes. With sham inhalation (n = 15), eNO levels
      did not change significantly from baseline, although a small decrease occurred.
      ETS exposure (n = 15) resulted in a rapid fall in eNO from mean (SE) 134 (29) ppb
      to 102 (22) ppb, or by 23.6% (p < 0.05), and remained low for 60 minutes. With
      active smoking (n = 7), levels fell acutely from baseline within the same time
      interval (71 [16] to 49 [11] ppb, or by 30.3%), and remained low. These changes
      were significant compared with sham exposure for both ETS (p < 0.05) and active
      smoke inhalation (p <.01). This suggests that eNO can be used for the
      investigation of the mechanisms of cigarette-induced lung damage in the
      experimental setting, and may potentially be useful also for environmental
      assessment of ETS effects.

PMID- 11587996
TI  - Immunohistochemical detection of human basophils in postmortem cases of fatal
      asthma.
AB  - The role of human basophils in bronchial asthma has been hard to define. In this
      study, we used the basophil-specific monoclonal antibody (mAb), 2D7, in
      postmortem lung sections from individuals who die in status asthmaticus (fatal
      asthma [FA]) to determine if the pathology of FA is associated with an increase
      in basophil numbers in the lung. As controls, we used lung sections of patients
      who had a history of asthma but died from nonasthmatic causes (nonfatal asthma
      [NFA]) as well as patients with no history of asthma (control [C]). In lung
      sections from all three groups, basophils were scattered throughout the large and
      small airways, airway epithelium, submucosa, and alveolar walls. The numbers of
      basophils in the lungs of patients with FA ranged from 41 to 119 cells/mm(2),
      significantly more than the numbers of basophils in lungs from individuals with a
      history of asthma (NFA; 0 to 16 cells/ mm(2)) and in the control lungs (C; 0 to
      13 cells/mm(2)). In contrast, CD45-positive cells were not significantly
      different in the airways of FA and NFA, although there were significant increases
      in the two groups compared with control subjects. In summary, basophil
      infiltration was significantly increased in lungs from individuals who died from
      asthma, supporting the hypothesis that basophils are involved in the pathogenesis
      of FA.

PMID- 11587995
TI  - Effects of budesonide and formoterol on NF-kappaB, adhesion molecules, and
      cytokines in asthma.
AB  - The asthmatic inflammatory response can be attenuated by corticosteroids and in
      part by beta(2)-agonists. We investigated if these effects are accompanied by a
      downregulation in nuclear factor kappa B (NF-kappaB), a transcription factor
      regulating many of the cytokine and adhesion molecule genes expressed in allergic
      inflammation. Bronchial biopsies were taken before and after 8 wk treatment with
      formoterol, budesonide, or placebo from atopic asthmatics. Biopsies were
      processed into glycol methacrylate and stained immunohistochemically for
      eosinophils (as an index of inflammation), activated and total NF-kappaB,
      adhesion molecules, and cytokines. After budesonide treatment there was a
      significant decrease in the number of submucosal cells staining for total NF
      kappaB, granulocyte macrophage colony-stimulating factor (GM-CSF) and tumor
      necrosis factor-alpha (TNF-alpha), accompanied by a significant decrease in
      mucosal eosinophils and expression of vascular cell adhesion molecule-1 (VCAM-1)
      in the endothelium and interleukin-8 (IL-8) in the epithelium. After formoterol
      treatment there was a significant decrease in eosinophils and the epithelial
      expression of activated NF-kappaB, but these changes were not accompanied by
      reduced immunoreactivity for adhesion molecules or cytokines. We conclude that at
      least some of the therapeutic efficacy of inhaled corticosteroids is mediated
      through inhibition of NF-kappaB-regulated gene expression, whereas the reduction
      in airway eosinophilia by long-acting beta(2)-agonists probably operates through
      alternative pathways.

PMID- 11587997
TI  - In silico cloning of mouse Muc5b gene and upregulation of its expression in mouse
      asthma model.
AB  - Using a BLAST-searching approach, we identified a mouse expressed sequence tag
      (EST) clone (AA038672) showing great similarity to the 3' end of the human MUC5B
      gene. The clone was named "3pmmuc5b-1" after complete nucleotide sequencing
      (Genbank Accession, AF369933). A subsequent search of the mouse genome database
      with the 3pmmuc5b-1 sequence identified two overlapping genomic clones (AC020817
      and AC020794) that contained the sequence of both 3pmmuc5b-1 and the mouse Muc5ac
      gene. Like their human homologs, the genomic order of the mouse Muc genes is 5'
      Muc5ac-Muc5b-3'. These results suggest that the newly identified EST clone,
      3pmmuc5b-1, is part of the 3' portion of the mouse Muc5b gene. In situ
      hybridization demonstrated that this putative mouse Muc5b message was expressed
      in a restricted manner in the sublingual gland region of the tongue and the
      submucosal gland region of the mouse trachea in a normal animal. However, the
      gene expression was greatly enhanced in airway surface epithelium and the
      submucosal gland region in ovalbumin-induced asthmatic mice. These results were
      consistent with previous studies of human airway tissues. We therefore conclude
      that this newly cloned mouse Muc5b gene could be used as a marker for studying
      aberrant mucin gene expression in mouse models of various airway diseases.

PMID- 11587998
TI  - Lung tissue mechanics and extracellular matrix remodeling in acute lung injury.
AB  - This study was undertaken to test whether there is structural remodeling of lung
      parenchyma that could lead to tissue mechanical changes at an early phase of
      varying degrees of acute lung injury (ALI). Tissue resistance (R), dynamic
      elastance (E), and hysteresivity (eta) were analyzed during sinusoidal
      oscillations of rat lung parenchymal strips 24 h after intraperitoneal injection
      of saline (C) or paraquat (P [10, 15, 25, and 30 mg/kg]). These strips were also
      stained in order to quantify the amount of collagen and of three types of elastic
      fibers (elaunin, oxytalan, and fully developed elastic fibers) in the alveolar
      septa. E augmented progressively from C to P25, but the data from the P25 and P30
      groups were not different (p < 0.0001). R and eta increased from C to P10 and
      from P15 to P25 (p < 0.001). Collagen fiber content increased exponentially with
      the severity of the injury. Elaunin and fully developed elastic fibers remained
      unchanged in the five groups, while oxytalan fibers increased only in the P25 and
      P30 groups. In conclusion, the pronounced mechanical changes at the tissue level
      and fibroelastogenesis happened at an early phase of the disease and even in
      mildly abnormal lung parenchyma. KEYWORDS: elastance; collagen fibers; elastin;
      paraquat

PMID- 11587999
TI  - Reversible airflow obstruction, proliferation of abnormal smooth muscle cells,
      and impairment of gas exchange as predictors of outcome in
      lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a rare disease, occurring in women,
      characterized by cystic degeneration of the lungs, abdominal tumors, and
      proliferation of abnormal smooth muscle cells. Lung function abnormalities
      consist of impairment of the diffusion capacity (DL(CO)) and airflow obstruction.
      The objective of this study was to correlate the functional impairment with
      histologic measures of disease severity to identify predictors of disease
      outcome. Lung function of 143 patients and lung biopsies of 74 of these patients
      were reviewed for evidence of airway disease and scoring of disease severity. A
      positive response to bronchodilators was associated with more severe airflow
      obstruction, a predominantly solid pattern of LAM lesions in the lung biopsy, and
      greater rate of decline in expiratory flow. Airway inflammation, present in 61%
      of the lung specimens, was not associated with reversible airway obstruction and
      did not correlate with the severity of airflow obstruction. DL(CO) correlated
      best with the LAM histologic score (LHS), a demonstrated predictor of outcome. We
      conclude that reversible airway obstruction is found in LAM patients with
      accelerated loss of lung function and a predominantly solid pattern of LAM
      lesions. Impairment of DL(CO) correlates with LHS, a predictor of survival and
      time to lung transplantation.

PMID- 11588000
TI  - Differential properties of mucous glycoproteins in rat nasal epithelium. A
      comparison between allergic inflammation and lipopolysaccharide stimulation.
AB  - To examine the differential properties of mucous glycoproteins, we produced
      hypertrophic and metaplastic changes in goblet cells of rat nasal epithelium by
      intranasal instillation of ovalbumin (OVA) in OVA-sensitized rats, and by
      intranasal lipopolysaccharide (LPS) instillation. The epithelial mucosubstance
      was quantitatively examined by alcian blue-periodic acid-Schiff (AB-PAS) and
      lectin histochemistry. The newly produced mucin after OVA challenge or LPS
      instillation contained a high amount of sulfomucin and a low amount of neutral
      glycoprotein: LPS-induced mucin contained more sulfomucin (70.1% of total) and
      less neutral glycoprotein (8.6%) than OVA-induced mucin (sulfomucin, 33.6%;
      neutral glycoprotein, 41.8%; p < 0.01). Four of the lectins stained some of the
      mucosubstance, indicating the presence of galactose-N-acetylgalactosamine,
      alpha2,3- and alpha2,6-linked sialic acid-galactose, and fucose residues. After
      LPS instillation, the reactivity was higher for galactose-N-acetylgalactosamine
      (64.8% of total) and alpha2,3-linked sialic acid-galactose (75.8%) than after
      saline instillation (3.5 and 19.1%, respectively) or OVA challenge (5.8 and
      32.3%; p < 0.05). OVA challenge did not induce the alteration of terminal sugar
      residues. A 2-fold increase in mucin mRNA (rat Muc5ac) expression was induced
      after LPS instillation or OVA challenge, compared with animals treated with
      saline instillation (p < 0.05). These results indicate that mucin mRNA expression
      (for peptide backbone) increases similarly after LPS instillation or OVA
      challenge; however, carbohydrate compositions of newly produced mucin are
      different between the two groups.

PMID- 11588001
TI  - Restoring effects of vitamin A on surfactant synthesis in nitrofen-induced
      congenital diaphragmatic hernia in rats.
AB  - Congenital diaphragmatic hernia (CDH) is a major cause of refractory respiratory
      failure in the newborn. Besides pulmonary hypoplasia, the pathophysiology of CDH
      also includes surfactant deficiency. Vitamin A (vit A) is important for various
      aspects of lung development. We hypothesized that antenatal treatment with vit A
      would stimulate lung surfactant synthesis in experimental CDH induced in rats by
      maternal ingestion of the herbicide nitrofen (2,4-dichloro-phenyl-p-nitrophenyl
      ether) on Day 12. Fetuses were assigned to six experimental groups: (1) controls
      from rats that received olive oil, the vehicle; (2) fetuses from rats that
      received olive oil on Day 12 and vit A orally (15,000 IU) on Day 14; (3) nitrofen
      (N)-exposed fetuses without diaphragmatic hernia (N/no DH); (4) N/no DH from rats
      given vit A on Day 14; (5 ) nitrofen-exposed fetuses with DH (N/+DH); (6) N/+DH
      from rats given vit A on Day 14. Fetuses were delivered by C-section at Day 21.
      Lung DNA content was lowered in the nitrofen group as compared with the controls
      group, but increased by subsequent vit A treatment. Lung surfactant disaturated
      phosphatidylcholine was reduced in the N/+DH group and restored to control level
      by vit A. The expression level of surfactant proteins (SP) -A and -C was
      decreased in vit A-treated control rats and in nitrofen-exposed fetuses with or
      without DH. Vit A restored SP-A and -C mRNA expression to control levels in
      N/+DH. SP-B expression was lowered in N/no DH and increased by vit A in this
      group. The proportion of type II cells assessed by SP-B immunolabeling was
      lowered in N/+DH and restored by vit A treatment. We conclude that antenatal
      treatment with vit A restores lung maturation in nitrofen-induced hypoplastic
      lungs with CDH. These findings point out vit A as a potential therapeutical agent
      for correcting surfactant deficiency in CDH.

PMID- 11588002
TI  - Particulate matter induces cytokine expression in human bronchial epithelial
      cells.
AB  - The present study was designed to determine cytokines produced by primary human
      bronchial epithelial cells (HBECs) exposed to ambient air pollution particles
      (EHC-93). Cytokine messenger RNA (mRNA) was measured using a ribonuclease
      protection assay and cytokine protein production by enzyme-linked immunosorbent
      assay. Primary HBECs were freshly isolated from operated lung, cultured to
      confluence, and exposed to 10 to 500 microg/ml of a suspension of ambient
      particulate matter with a diameter of less than 10 microm (PM(10)) for 2, 8, and
      24 h. The mRNA levels of leukemia inhibitory factor (LIF), granulocyte macrophage
      colony-stimulating factor (GM-CSF), interleukin (IL)-1alpha, and IL-8 were
      increased after exposure to PM(10), and this increase was dose-dependent between
      100 (P < 0.05) and 500 (P < 0.05) microg/ml of PM(10) exposure. The
      concentrations of LIF, GM-CSF, IL-1beta, and IL-8 protein measured in the
      supernatant collected at 24 h increased in a dose- dependent manner and were
      significantly higher than those in the control nonexposed cells. The soluble
      fraction of the PM(10) (100 microg/ml) did not increase these cytokine mRNA
      levels compared with control values and were significantly lower compared with
      HBECs exposed to 100 microg/ml of PM(10) (LIF, IL-8, and IL-1beta; P < 0.05),
      except for GM-CSF mRNA (P = not significant). We conclude that primary HBECs
      exposed to ambient PM(10) produce proinflammatory mediators that contribute to
      the local and systemic inflammatory response, and we speculate that these
      mediators may have a role in the pathogenesis of cardiopulmonary disease
      associated with particulate air pollution.

PMID- 11588003
TI  - Human leukocyte antigen-DRB1 position 11 residues are a common protective marker
      for sarcoidosis.
AB  - Genetic factors, in particular human leukocyte antigens (HLAs) are important
      determinants of susceptibility to sarcoidosis, a chronic granulomatous disease of
      undetermined etiology. To clarify the role of HLA in sarcoidosis we determined
      HLA-DR and -DQ alleles in case-control samples from three European populations
      (United Kingdom, Czech, and Polish) and compared these results with those
      published for three additional populations (Italian, Japanese, and Scandinavian)
      to determine whether the HLA-DR and/or -DQ alleles act as ethnic-dependent, or
      ethnic-independent modifiers of disease risk. Although variations were apparent
      in the alleles associated with susceptibility, reductions in the frequency of
      alleles associated with protection were remarkably consistent in the six
      populations. Previously detected associations between single-nucleotide
      polymorphisms at the TAP2 locus and sarcoidosis were shown to be due to linkage
      disequilibrium with the HLA-DR locus. The protective HLA-DR alleles, which encode
      the DR1 and DR4 antigens, were found to share characteristic small hydrophobic
      residues at position 11, which were replaced by small hydrophilic residues in the
      remaining, nonprotective, HLA-DR alleles. This residue position is within a
      pocket of the HLA-DR complex antigen binding groove (designated P6), where it is
      the only variable amino acid and therefore determines the peptide binding
      preferences of this pocket. A highly significant reduction in the frequency of
      individuals carrying HLA-DR alleles with a hydrophobic residue at position 11 was
      observed in the sarcoidosis cases in the three populations we examined. This
      suggests this HLA-DR residue is an important protective marker in sarcoidosis.

PMID- 11588004
TI  - Laser capture microdissection and real-time reverse transcriptase/ polymerase
      chain reaction of bronchiolar epithelium after bleomycin.
AB  - Terminal airways are affected in many lung diseases and toxic inhalations. To
      elucidate the changes in terminal airways in these diverse situations it will be
      helpful to profile and quantify gene expression in terminal bronchiolar
      epithelium. We used laser capture microdissection (LCM) to collect terminal
      bronchiolar epithelial cells from frozen sections of lungs of mice subjected to
      intratracheal bleomycin. The RNA from these cells was used for analysis of select
      messenger RNAs (mRNAs) by quantitative real-time polymerase chain reaction (PCR).
      In parallel, we used real-time PCR to analyze mRNAs in whole-lung homogenates
      prepared from other mice given intratracheal bleomycin. We found reductions of
      Clara cell-specific protein and keratinocyte growth factor receptor mRNAs in both
      terminal bronchiolar epithelium and whole-lung homogenates 7 d after bleomycin.
      In contrast, terminal bronchiolar epithelial transforming growth factor (TGF)
      alpha mRNA was reduced but whole-lung TGF-alpha mRNA was not changed, whereas
      terminal bronchiolar epithelial epidermal growth factor (EGF) receptor mRNA was
      not changed but whole-lung EGF receptor was reduced. We conclude that LCM can
      isolate terminal bronchiolar epithelial cells for studies of cell-specific gene
      expression by quantitative real-time PCR, and that cell-specific gene expression
      in terminal bronchiolar epithelium is not necessarily reflected in analysis of
      whole-lung gene expression.

PMID- 11588005
TI  - Basic electrical properties of in situ endothelial cells of small pulmonary
      arteries during postnatal development.
AB  - Small pulmonary arteries are the major determinants of pulmonary artery pressure
      and vascular resistance. Their endothelium modulates pulmonary resistance,
      remodeling, and blood fluidity. We developed a method that provides access to the
      luminal surface of small pulmonary arteries of rat and allows the patch-clamp
      study of electrical properties of in situ endothelium. At birth, the membrane was
      predominantly permeable for K(+), showing a resting potential of -70 mV. This
      conductance was not voltage-dependent and was insensitive to standard blockers of
      K(+) channels such as tetraethylammonium, charybdotoxin, and 4-aminopyridine. The
      first 22 d of development were accompanied by an additional expression of a Cl(-)
      conductance, increasing membrane potential to -45 mV. Acidosis reduced K(+)
      conductance and depolarized the membrane, whereas alkalosis resulted in
      hyperpolarization. Two-electrode recordings revealed tight electrical coupling
      (83%) between neighboring cells in the circumferential direction of the artery.
      The electrotonic length constant for endothelium was 13.3 microm, indicating that
      most cells in one cross section of a small artery are well coupled. Thus, the
      resting membrane conductances in small pulmonary artery endothelial cells change
      with postnatal development and are modulated by pH.

PMID- 11588006
TI  - Role of lysophosphatidylcholine in the desensitization of beta-adrenergic
      receptors by Ca(2+) sensitization in tracheal smooth muscle.
AB  - Lysophosphatidylcholine (Lyso-PC) is generally considered to promote tissue
      inflammation. To determine the involvement of exogenous Lyso-PC in the beta
      adrenergic desensitization by phospholipase A2, we examined the inhibitory
      effects of isoproterenol (ISO) on tension and intracellular Ca(2+) concentration
      by methacholine (MCh) after continuous exposure to Lyso-PC in guinea-pig tracheal
      smooth muscle, using isometric tension recordings and fura-2 signal (F340/F380
      ratio). Pre- exposure to 10 microM Lyso-PC markedly reduced subsequent inhibition
      by 0.3 microM ISO against 1 microM MCh-induced contraction in a time-dependent
      manner. In contrast, values of percent F340/F380 ratio for MCh with ISO were not
      affected after exposure to Lyso-PC. In the presence of Y-27632, a selective rho
      kinase inhibitor, a reduction in subsequent relaxation by ISO after exposure to
      Lyso-PC was inhibited in a concentration-dependent manner. Preincubation with
      cholera toxin also inhibited reduced responsiveness to ISO by Lyso-PC. Pre
      exposure to Lyso-PC did not attenuate subsequent relaxation by agents that bypass
      beta-adrenergic receptors. These results indicate that continuous exposure to
      Lyso-PC may cause homologous desensitization of beta-adrenergic receptors via an
      augmentation in sensitivity to Ca(2+) by rho, a small G protein, in airway smooth
      muscle, and that activation of the stimulatory G protein of adenylyl cyclase,
      G(s), may prevent this phenomenon.

PMID- 11588007
TI  - Chronic smoking enhances tachykinin synthesis and airway responsiveness in guinea
      pigs.
AB  - This study tests the hypothesis that the bronchial hyperreactivity induced by
      chronic cigarette smoke (CS) exposure involves the increased expression and
      release of tachykinins and calcitonin gene-related peptide (CGRP) from afferent
      nerve fibers innervating the airways. In guinea pigs chronically exposed to CS
      (20 min twice daily for 14-17 d), peak response in total lung resistance to
      capsaicin (1.68 microg/kg, intravenously) was significantly greater than that
      evoked by the same dose of capsaicin in control (air-exposed) animals. This
      augmented response in CS-exposed animals was abolished after treatment with CP
      99994 and SR-48968, the neurokinin (NK)-1 and NK-2 receptor antagonists,
      suggesting the involvement of tachykinins in chronic CS-induced airway
      hyperresponsiveness (AHR). Further, substance P (SP)-like immunoreactivity (LI)
      and CGRP-LI in the airway tissue were significantly greater in the CS animals
      than in the control animals. Finally, beta-preprotachykinin (PPT, a splice
      variant from the PPT A gene encoding tachykinins including SP and NKA) messenger
      RNA levels as measured by in situ hybridization histochemistry displayed a
      significant increase in jugular ganglion neurons but not in dorsal root or nodose
      ganglion neurons. These data suggest that chronic CS-induced AHR is related to an
      increase in SP synthesis and release in jugular ganglion neurons innervating the
      lungs and airways.

PMID- 11588008
TI  - Secretion in alveolar type II cells at the interface of constitutive and
      regulated exocytosis.
AB  - Long-term, simultaneous, measurements of cytoplasmic free Ca(2+) concentrations
      and single exocytotic fusion events in surfactant-secreting type II cells were
      performed. All fusion (constitutive, phorbol ester-induced, and agonist-induced)
      was Ca(2+)-dependent. Kinetic analysis revealed that agonist (adenosine
      triphosphate [ATP])-induced fusion exhibited a kinetic pattern that correlated
      well with the Ca(2+) signal. The effects of Ca(2+) release from intracellular
      stores (early) and Ca(2+) entry (late) could be demonstrated for the first time
      by dissecting the slow (10-to-15-min) fusion response to ATP into these two
      components. Bath Ba(2+) or Sr(2+) could replace Ca(2+) to elicit a fusion
      response in thapsigargin-pretreated cells lacking ATP-induced Ca(2+) release from
      stores. Although the late response was partially inhibited by interrupting the
      phospholipase D-protein kinase C axis, a high Ca(2+) dependence of the entire
      secretory course was demonstrated by a significant correlation between the
      integrated Ca(2+) signal and the fusion response. There was also a highly
      significant correlation between constitutive and ATP-stimulated fusion activity
      in individual cells. We propose a common mechanistic model for all types of
      fusion in this slow secretory cell, in which constitutive and regulated forms of
      exocytosis are subject to the same principles of regulation.

PMID- 11588009
TI  - Differential adrenomedullin release and endothelin receptor expression in
      distinct subpopulations of human airway smooth-muscle cells.
AB  - Although adrenomedullin (ADM) is implicated in the control of airway tone,
      regulation of ADM release from airway smooth-muscle cells (ASMCs) has not been
      explored. Preliminary experiments have indicated that human ASMC populations were
      heterogeneous in their rate of ADM release and expression of endothelin (ET)(A)
      and ET(B) receptors. We isolated these phenotypically distinct ASMCs from
      explants derived from the same airway segment. ASMCs possessing exclusively ET(A)
      receptors appeared smaller and proliferated faster than ET(A)/ET(B) isolates.
      Macroautoradiographic analysis confirmed the presence of both receptors in human
      bronchi. ADM release and messenger RNA expression was greater in ET(A)/ET(B)
      isolates compared with ET(A) isolates. No measurable ET release was detected from
      ASMCs. Exogenous ET-1 (1 to 100 nM) more potently stimulated the release of ADM
      from ET(A)/ET(B) compared with ET(A) isolates. In addition, ET-3 (1 to 100 nM)
      stimulated ADM release only from ET(A)/ET(B) isolates, implicating the ET(B)
      receptor in this response. Exogenous ET-1 potentiated platelet- derived growth
      factor-stimulated [3H]thymidine uptake in ET(A)/ ET(B) but not ET(A) isolates. ET
      3 did not affect [3H]thymidine uptake in either cell type. Possession of
      ET(A)/ET(B) receptors is associated with higher rates of ADM release and slower
      proliferation, but a capacity for ET-1 stimulated DNA synthesis via ET(A)
      receptors. These results support a paracrine role for the regulation of ADM
      release predominantly via the ET(B) receptor in human ASMCs.

PMID- 11588010
TI  - Temporal-spatial analysis of the immune response in a murine model of ovalbumin
      induced airways inflammation.
AB  - The objective of this study was to define phenotypic changes of antigen
      presenting cells (APCs) and T cells in a murine model of antigen-induced airways
      inflammation that involves intraperitoneal sensitization with ovalbumin
      (OVA)/adjuvant followed by antigen aerosolization. We investigated the APC and T
      cell compartments both after sensitization (primary immune response) and after
      challenge (secondary immune response) at the thoracic lymph nodes (initiation
      site) and the lung (effector site). Our findings document a major cellular
      expansion in the lymph nodes after both sensitization and challenge. After
      sensitization, this expansion was comprised mainly of B cells, a considerable
      proportion of which expressed B7.2. At this time, T cells were markedly expanded
      and activated as assessed by CD69 expression; further, although GATA-3 and signal
      transducer and activator of transcription-6 were expressed at this time point,
      expression of interleukin (IL)-4, IL-5, and IL-13 messenger RNA (mRNA) levels
      were marginal. However, in vitro stimulation of lymph-node cells with OVA led to
      cytokine production. In contrast, 24 h after challenge, but not after
      sensitization, there was a major expansion of dendritic cells and macrophages in
      the lungs. This expansion was associated with enhanced expression of both B7.1
      and B7.2. We also observed expansion of activated CD3(+)/CD4(+) T cells
      expressing the T helper-2-associated marker T1/ST2 in the lung, most notably 5 d
      after challenge. Further, IL-4, IL-5, and IL-13, but not interferon-gamma mRNA
      were expressed at high levels 3 h after challenge. This study helps to elucidate
      the "geography" of immune responses generated in a conventional murine model of
      allergic airways inflammation.

PMID- 11588011
TI  - Interleukin-17 and lung host defense against Klebsiella pneumoniae infection.
AB  - Bacterial pneumonia remains an important cause of morbidity and mortality
      worldwide, especially in immune-compromised patients. Cytokines and chemokines
      are critical molecules expressed in response to invading pathogens and are
      necessary for normal lung bacterial host defenses. Here we show that interleukin
      (IL)-17, a novel cytokine produced largely by CD4+ T cells, is produced in a
      compartmentalized fashion in the lung after challenge with Klebsiella pneumoniae.
      Moreover, overexpression of IL-17 in the pulmonary compartment using a
      recombinant adenovirus encoding murine IL-17 (AdIL-17) resulted in the local
      induction of tumor necrosis factor-alpha, IL-1beta, macrophage inflammatory
      protein-2, and granulocyte colony-stimulating factor (G-CSF); augmented
      polymorphonuclear leukocyte recruitment; and enhanced bacterial clearance and
      survival after challenge with K. pneumoniae. However, simultaneous treatment with
      AdIL-17 provided no survival benefit after intranasal K. pneumoniae challenge.
      These data show that IL-17 may have a role in priming for enhanced chemokine and
      G-CSF production in the context of lung infection and that optimally timed gene
      therapy with IL-17 may augment host defense against bacterial pneumonia.

PMID- 11588012
TI  - Distribution and mRNA expression of tenascin-C in developing human lung.
AB  - Tenascin-C is an extracellular matrix glycoprotein that is spatially expressed
      during organogenesis, in inflammatory and fibrotic disorders, and in neoplasms.
      The aim of this study was to analyze its expression in developing human lung
      tissues during pseudoglandular, canalicular, saccular, and alveolar periods
      corresponding to Weeks 12 to 40. Lung tissues were obtained at autopsy from 34
      nonmalformed cases. An immunohistochemical analysis and a messenger RNA (mRNA) in
      situ hybridization method combined with light microscopy were used. The extent of
      tenascin-C immunoreactivity was scored as absent, low, moderate, or strong in and
      around different types of pulmonary cells. The immunohistochemical expression for
      tenascin-C was strong beneath the airway epithelium, especially at the sites of
      airway subdivision during Weeks 12 to 23, whereas its expression was moderate or
      weak underneath alveolar and bronchiolar epithelia between Weeks 24 and 40. The
      expression for tenascin-C was strong in the intima of veins, especially in the
      canalicular period, i.e., Weeks 17 to 28. A moderate or strong immunoreactivity
      for tenascin-C was also observed around chondrocytes in every case studied during
      all periods. The increased expression of tenascin-C mRNA was most often seen in
      the cells below the airway epithelium. Taken together, tenascin-C is expressed in
      human lung during all developmental periods, and its expression is especially
      strong below the airway epithelium at the sites of airway subdivision.

PMID- 11588013
TI  - Il-9 stimulates release of chemotactic factors from human bronchial epithelial
      cells.
AB  - Interleukin (IL)-9 is a T helper 2 cytokine implicated as a candidate gene and
      contributor to human asthma. We hypothesized that the inflammatory potential of
      bronchial epithelium is affected by its local environment and explored this
      hypothesis with respect to the effect of IL-9 on bronchial epithelium. We
      investigated the response of primary and immortalized human bronchial epithelial
      cells to IL-9 stimulation with respect to the release of T-cell chemoattractant
      factors. In response to IL-9, the HBE4-E6/E7 cell line, but not BEAS-2B cells,
      released the T-cell chemoattractants IL-16 and regulated on activation, normal T
      cells expressed and secreted (RANTES) in a dose-dependent fashion. We found a
      similar dose response to IL-9 in primary cells from bronchial brushings of
      healthy subjects and that nearly all of the T-cell chemoattraction was
      attributable to IL-16 and RANTES. Reverse transcriptase/polymerase chain reaction
      of BEAS-2B, HBE4-E6/E7, and primary cells from two subjects revealed messenger
      RNA for IL-9 receptor (IL-9R) alpha but not in BEAS-2B cells. Fluorescence
      activated cell sorter analysis of HBE4-E6/E7 and primary cells confirmed surface
      expression of the IL-9 receptor. Costimulation of both cell types with IL-9 and
      antibody to either gamma-common chain or IL-9Ralpha completely blocked the
      release of T-cell chemoattractant activity, confirming the primary role of a
      functioning IL-9 receptor for IL-9 signaling in HBE4-E6/E7 and primary bronchial
      epithelial cells. We conclude that IL-9 is a stimulus for airway epithelial cell
      release of T-cell chemoattractant factors, which in turn may modulate the immune
      response in allergic airway inflammation.

PMID- 11588014
TI  - Rat alveolar type II cells inhibit lung fibroblast proliferation in vitro.
AB  - Fibroblasts stimulate alveolar type II epithelial cell differentiation and
      proliferation in vitro and during lung development. However, little is known
      about the effects of adult type II cells on fibroblasts. We investigated the
      effect of adult rat type II cells on proliferation of adult human lung
      fibroblasts. Fibroblasts were suspended within rat tail collagen which was gelled
      on a floating polycarbonate filter, and type II cells were cultured on Matrigel.
      In this coculture system, alveolar type II cells inhibited fibroblast
      proliferation and indomethacin blocked the inhibitory effect on fibroblast
      growth. Prostaglandin (PG) E2, the major PG secreted by type II cells, inhibited
      fibroblast proliferation and was increased during the period of inhibition of
      fibroblast proliferation. Incubation with arachidonate showed that most of the
      PGE2 in the coculture system was produced by the fibroblasts. In addition, we
      found that rat type II cells also inhibited rat fibroblasts and that inhibition
      of fibroblast growth by type II cells could be stimulated by keratinocyte growth
      factor. We conclude that in this coculture system, type II cells inhibit
      fibroblast proliferation by secreting a factor(s) that stimulates PGE2 production
      by fibroblasts, and that PGE2 directly inhibits fibroblast proliferation.

PMID- 11588015
TI  - Type II pneumocyte-CD8+ T-cell interactions. Relationship between target cell
      cytotoxicity and activation.
AB  - CD8+ T-cell responses play an important role in the clearance of respiratory
      virus infection, but may also contribute to lung injury in the process. The
      effector mechanisms involved in viral clearance and associated lung injury
      include both cytolytic and noncytolytic effector functions. Previously we have
      shown that CD8+ T-cell recognition of alveolar epithelial cells triggers
      chemokine expression by the epithelial cell and that this plays an important role
      in the inflammatory infiltration that ensues in the context of T cell-mediated
      injury (Zhao and colleagues, J. Clin. Invest. 2000;106:R49-R58). In the present
      study we sought to understand the relationship between alveolar cell cytotoxicity
      and chemokine expression, both of which occur as a result of CD8+ T-cell antigen
      recognition. Alveolar epithelial cells efficiently process and present
      overlapping viral epitopes, and CD8+ T-cell recognition of these class I major
      histocompatibility complex-restricted epitopes resulted in cytotoxicity of the
      alveolar cells by both wild-type and perforin-deficient T cells. However, the
      contribution of perforin-mediated lysis to the total cytotoxicity of alveolar
      cells by CD8+ T cells was minimal, and the majority of the lysis was attributable
      to tumor necrosis factor-alpha expressed by the T cell. CD8+ T-cell recognition
      also led to activation of nuclear factor-kappaB in the alveolar epithelial target
      cells, at levels inversely proportional to the effector/target (E:T) ratio.
      Finally, at varying E:T ratios, we demonstrated an inverse relationship between
      alveolar cell cytotoxicity and monocyte chemotactic protein-1 expression, both of
      which occur as a result of T-cell recognition. These findings may have important
      ramifications in understanding the relationship between viral clearance and lung
      injury.

PMID- 11588016
TI  - Differential regulations between adenosine triphosphate (ATP)- and uridine
      triphosphate-induced Cl(-) secretion in bovine tracheal epithelium. Direct
      stimulation of P1-like receptor by ATP.
AB  - Adenosine 5'-triphosphate (ATP) stimulates airway epithelial Cl(-) secretion in a
      complicated manner. We examined the difference between ATP- and uridine 5'
      triphosphate (UTP)-induced responses of short-circuit current (Isc) in bovine
      tracheal epithelium treated with amiloride. Each nucleotide caused an increase in
      Isc composed of the first and second peaks, where the second peak induced by ATP
      was higher compared with UTP. The ATP-induced second peak was inhibited by the
      protein kinase (PK) A inhibitor H89, saturation of P1 receptor with adenosine,
      and the P1 receptor antagonist 8-p-sulfophenyltheophylline, but not by the Ca(2+)
      chelator ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid
      plus the endoplasmic reticulum Ca(2+)-pump inhibitor thapsigargin, the adenosine
      breakdown enzyme adenosine deaminase, the ectonucleotidase inhibitor alpha,beta
      methyleneadenosine 5'-diphosphate, or saturation of P2Y2 receptor with UTP. Thus,
      the response is associated with PKA-dependent pathway via P1-like receptor but
      not with Ca(2+)-dependent pathway via P2Y2 receptor, and ATP degradation products
      do not contribute to this response. Further, stimulation of cells with ATP
      increased PKA activity. In addition, pretreatment with glybenclamide, an
      inhibitor of cystic fibrosis transmembrane conductance regulator, reduced the
      second peak of Isc induced by ATP but was without effect on that induced by UTP.
      Therefore, ATP stimulates glybenclamide-sensitive Cl(-) secretion, and this
      action is partly mediated by PKA-dependent pathway via P1-like receptor.

PMID- 11588017
TI  - Identification and association of polymorphisms in the interleukin-13 gene with
      asthma and atopy in a Dutch population.
AB  - Asthma and atopy are related conditions that may share similar genetic
      susceptibility. Linkage studies have identified a region on chromosome 5q that
      contains biologic candidates for both asthma and atopy phenotypes, including
      several proinflammatory cytokines. Interleukin (IL)-13, one of the candidate
      genes in the region, is directly involved in the regulation of immunoglobulin E
      and has been associated with both asthma and atopy. We sought to identify new
      polymorphisms in the IL-13 gene, and evaluated the involvement of a subset of
      these variants in asthma and atopy in a case-control study using probands and
      spouses from a Dutch asthma family study. IL-13 was sequenced in 20 probands and
      20 unaffected spouses, and 10 polymorphisms were identified, four novel and six
      previously reported. Three single nucleotide (nt) polymorphisms (SNPs) were
      detected in the 5'-promoter region, two in intron 1, and five in exon 4. Only one
      of the exon 4 SNPs resulted in an amino-acid change (Arg130Gln). We analyzed
      three SNPs in IL-13 in an extended group of 184 probands and their spouses: one
      in the promoter region (-1111), the Arg130Gln (nt position 4257), and a 3'
      untranslated region SNP (nt position 4738). The most significant associations
      were observed to asthma (P = 0.005), bronchial hyperresponsiveness (P = 0.003),
      and skin-test responsiveness (P = 0.03) with the -1111 promoter. These results
      provide evidence that variation in the IL-13 gene is involved in the pathogenesis
      of asthma and atopy. Further investigation is required to determine which
      specific alleles or combination of alleles contribute to these phenotypes, and
      the possible downstream effects of the resulting change in IL-13 levels or
      activity.

PMID- 11588019
TI  - An unexpected link between HCV and platelets.

PMID- 11588018
TI  - The contribution of interleukin (IL)-4 and IL-13 to the epithelial-mesenchymal
      trophic unit in asthma.
AB  - Interleukin (IL)-4 and IL-13 are key proinflammatory cytokines in asthma. Studies
      in transgenic mice show that both cytokines cause inflammation, but only IL-13
      causes subepithelial fibrosis, a characteristic feature of asthma. We compared
      the in vitro profibrogenic effects of IL-4 and IL-13 using bronchial fibroblasts
      from asthmatic subjects. In the presence of transforming growth factor (TGF)-beta
      the cells transformed into contractile myofibroblasts and expressed alpha-smooth
      muscle actin and procollagen I. IL-4 and IL-13 also stimulated proliferation, but
      were relatively ineffective in promoting myofibroblast transformation. TGF-beta
      was more potent than the cytokines in stimulating release of endothelin-1 and
      vascular endothelial growth factor, whereas IL-4 and IL-13 were more potent
      stimuli for eotaxin release. Although neither IL-4 nor IL-13 induced profibrotic
      responses, both cytokines caused a corticosteroid-insensitive stimulation of TGF
      beta2 release from primary bronchial epithelial cells. These data indicate that
      epithelial activation by IL-13 or IL-4 plays a critical role in initiating
      remodeling through release of TGF-beta2. TGF-beta2 then activates the underlying
      myofibroblasts to secrete matrix proteins and smooth muscle and vascular mitogens
      to propagate remodeling changes into the submucosa. In contrast, direct
      activation of submucosal fibroblasts by IL-4 and IL-13 has a proinflammatory
      effect via eotaxin release and recruitment of eosinophils into the airways.

PMID- 11588020
TI  - Leukemia stem cells and constitutive activation of NF-kappaB.

PMID- 11588021
TI  - C/EBPalpha and the G-CSF receptor gene--partners in granulopoiesis?

PMID- 11588022
TI  - The dynamics of hepatitis C virus binding to platelets and 2 mononuclear cell
      lines.
AB  - Hepatitis C virus (HCV) binds to platelets in chronically infected patients where
      free HCV constitutes only about 5% of total circulating virus. Free HCV
      preferentially binds to human mononuclear cell lines but free and complexed virus
      binds equally to platelets. The extent of free HCV binding to human Molt-4 T
      cells (which express CD81) and to human promonocytic U937 cells or to platelets
      (which do not express CD81) was similar. The binding of free HCV to the cell
      lines was saturated at a virus dose of 1 IU HCV RNA per cell but binding to
      platelets was not saturable. Human anti-HCV IgG, but not anti-CD81, markedly
      inhibited HCV binding to target cells in a dose-dependent manner. Human
      antibodies to HCV hypervariable region 1 of E2 glycoprotein partially inhibited
      viral binding to target cells. Recombinant E2 also inhibited viral binding to
      target cells in a dose-dependent manner, with the efficacy of this decreasing in
      the rank order of Molt-4 cells more than U937 cells more than platelets. In
      contrast to HCV, recombinant E2 bound to Molt-4 cells to an extent markedly
      greater than that apparent with U937 cells or platelets. These results suggest
      that the binding of HCV to blood cells is mediated by multiple cell surface
      receptors and that recombinant E2 binding may not be representative of the
      interaction of the intact virus with target cells.

PMID- 11588023
TI  - Nuclear factor-kappaB is constitutively activated in primitive human acute
      myelogenous leukemia cells.
AB  - Human acute myelogenous leukemia (AML) is thought to arise from a rare population
      of malignant stem cells. Cells of this nature, herein referred to as leukemic
      stem cells (LSCs), have been documented for nearly all AML subtypes and appear to
      fulfill the criteria for stem cells in that they are self-renewing and give rise
      to the cells found in many leukemic populations. Because these cells are likely
      to be critical for the genesis and perpetuation of leukemic disease, the present
      studies sought to characterize unique molecular properties of the LSC population,
      with particular emphasis on the transcription factor, nuclear factor-kappaB (NF
      kappaB). Previous experiments have shown that unstimulated human CD34(+)
      progenitor cells do not express NF-kappaB. In contrast, primary AML CD34(+) cells
      display readily detectable NF-kappaB activity as assessed by electrophoretic
      mobility shift assay and gene expression studies. Furthermore, detailed analyses
      of enriched AML stem cells (CD34(+)/CD38(-)/CD123(+)) indicate that NF-kappaB is
      also active in the LSC population. Given the expression of NF-kappaB in leukemic,
      but not normal primitive cells, the hypothesis that inhibition of NF-kappaB might
      induce leukemia-specific apoptosis was tested by treating primary cells with the
      proteasome inhibitor MG-132, a well-known inhibitor of NF-kappaB. Leukemic
      CD34(+)/CD38(-) cells displayed a rapid induction of cell death in response to MG
      132, whereas normal CD34(+)/CD38(-) cells showed little if any effect. Taken
      together, these data indicate that primitive AML cells aberrantly express NF
      kappaB and that the presence of this factor may provide unique opportunities to
      preferentially ablate LSCs.

PMID- 11588024
TI  - Estrogen-dependent E2a/Pbx1 myeloid cell lines exhibit conditional
      differentiation that can be arrested by other leukemic oncoproteins.
AB  - The molecular pathways of normal myeloid differentiation, as well as the
      mechanisms by which oncogenes disrupt this process, remain poorly understood. A
      major limitation in approaching this problem has been the lack of suitable cell
      lines that exhibit normal, terminal, and synchronous differentiation in the
      absence of endogenous oncoproteins and in response to physiologic cytokines, and
      whose differentiation can be arrested by ectopically expressed human
      oncoproteins. This report describes clonal, granulocyte-macrophage colony
      stimulating factor-dependent myeloid cell lines that exhibit these properties.
      The cell lines were established by conditional immortalization of primary murine
      marrow progenitors with an estrogen-regulated E2a/Pbx1-estrogen receptor fusion
      protein. Clones were identified that proliferated as immortalized blasts in the
      presence of estrogen, and that exhibited granulocytic, monocytic, or bipotential
      (granulocytic and monocytic) differentiation on estrogen withdrawal.
      Differentiation was normal and terminal as evidenced by morphology, cell surface
      markers, gene expression, and functional assays. The differentiation of the cells
      could be arrested by heterologous oncoproteins including AML1/ETO, PML/RARalpha,
      PLZF/RARalpha, Nup98/HoxA9, and other Hox proteins. Furthermore, the study
      examined the effects of cooperating oncoproteins such as Ras or Bcr/Abl, which
      allowed for both factor-independent proliferation and differentiation, or Bcl-2,
      which permitted factor-independent survival but not proliferation. These myeloid
      cell lines provide tools for examining the biochemical and genetic pathways that
      accompany normal differentiation as well as a system in which to dissect how
      other leukemic oncoproteins interfere with these pathways.

PMID- 11588025
TI  - Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated
      stage B and C chronic lymphocytic leukemia patients.
AB  - To comparatively assess first-line treatment with fludarabine and 2 anthracycline
      containing regimens, namely CAP (cyclophosphamide, doxorubicin plus prednisone)
      and ChOP (cyclophosphamide, vincristine, prednisone plus doxorubicin), in
      advanced stages of chronic lymphocytic leukemia (CLL), previously untreated
      patients with stage B or C CLL were randomly allocated to receive 6 monthly
      courses of either ChOP, CAP, or fludarabine (FAMP), stratified based on the Binet
      stages. End points were overall survival, treatment response, and tolerance. From
      June 1, 1990 to April 15, 1998, 938 patients (651 stage B and 287 stage C) were
      randomized in 73 centers. Compared to ChOP and FAMP, CAP induced lower overall
      remission rates (58.2%; ChOP, 71.5%; FAMP; 71.1%; P <.0001 for each), including
      lower clinical remission rates (CAP, 15.2%; ChOP, 29.6%; FAMP, 40.1%; P =.003).
      By contrast, median survival time did not differ significantly according to
      randomization (67, 70, and 69 months in the ChOP, CAP, and FAMP groups,
      respectively). Incidences of infections (< 5%) and autoimmune hemolytic anemia (<
      2%) during the 6 courses were similar in the randomized groups, whereas
      fludarabine induced, compared to ChOP and CAP, more frequent protracted
      thrombocytopenia (P =.003) and less frequent nausea-vomiting (P =.003) and hair
      loss (P <.0001). For patients with stage B and C CLL first-line fludarabine and
      ChOP regimens both provided similar overall survival and close response rates,
      and better results than CAP. However, there was an increase in clinical remission
      rate and a trend toward a better tolerance of fludarabine over ChOP that may
      influence the choice between these regimens as front-line treatments in patients
      with CLL.

PMID- 11588026
TI  - Intensive chemotherapy followed by allogeneic or autologous stem cell
      transplantation for patients with myelodysplastic syndromes (MDSs) and acute
      myeloid leukemia following MDS.
AB  - This study investigated the feasibility of allogeneic (alloSCT) and autologous
      stem cell transplantation (ASCT) as postconsolidation therapy for patients with
      myelodysplastic syndromes (MDSs) or acute myeloid leukemia after MDS. Patients
      with a histocompatible sibling were candidates for alloSCT and the remaining
      patients for ASCT. Remission-induction therapy consisted of 1 or 2 courses with
      idarubicin, cytarabine, and etoposide, followed by one intensive consolidation
      course with cytarabine and mitoxantrone. Initially, bone marrow cells were used
      for ASCT. Subsequently, mobilized blood stem cells were used in an attempt to
      shorten posttransplantation hypoplasia. With a median follow-up of 3.6 years the
      184 evaluable patients showed a 4-year survival rate of 26% and a median survival
      of 13 months. The remission-induction chemotherapy induced complete remission
      (CR) in 100 patients (54%). The 4-year disease-free survival (DFS) rate was 29%
      and the median DFS was 12 months. Twenty-eight of 39 patients (72%) with a donor
      were allografted in CR-1, including 2 patients who underwent transplantation in
      CR-1 without a consolidation course. Thirty-six of 59 patients (61%) without a
      donor received ASCT in CR-1. The 4-year DFS rates in the group of patients with
      or without a donor were 31% and 27%, respectively. The 4-year survival rates from
      CR were 36% and 33%, respectively. This large prospective study shows the
      feasibility of both alloSCT and ASCT. This treatment approach leads to a
      relatively high remission rate, and the majority of patients in remission
      received the SCT in CR-1. The ongoing study investigates whether this approach is
      better than treatment with chemotherapy only.

PMID- 11588027
TI  - Standardized, unrelated donor cord blood transplantation in adults with
      hematologic malignancies.
AB  - The potential role of unrelated donor cord blood transplantation (UD-CBT) in
      adults remains unclear. This study reports the results of UD-CBT in 22 adults
      with hematologic malignancies following conditioning with thiotepa, busulfan,
      cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine,
      and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis
      with cyclosporine and prednisone. Median age was 29 years (range, 18-46 years),
      and median weight was 69.5 kg (range, 41-85 kg). HLA match was 6 of 6 in 1 case,
      5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells
      infused was 1.71 x 10(7)/kg (range, 1.01 x 10(7)/kg to 4.96 x 10(7)/kg). All 20
      patients surviving more than 30 days had myeloid engraftment, and only 1, who
      received the lowest cell dose, developed secondary graft failure. Median time to
      reach an absolute neutrophil count of at least 0.5 x 10(9)/L was 22 days (range,
      13-52 days). Median time to platelets numbered at least 20 x 10(9)/L was 69 days
      (range, 49-153 days). Seven patients (32%) developed acute GVHD above grade II,
      and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4
      patients. Twelve patients remained alive and disease-free 3 to 45 months after
      transplantation. Disease-free survival (DFS) at 1 year was 53%. Age strongly
      influenced DFS (P =.01). For patients aged 30 years or younger, the DFS at 1 year
      was 73%. These preliminary results suggest that UD-CBT should be considered a
      reasonable alternative in young adults with hematologic malignancy and no
      appropriate bone marrow donor.

PMID- 11588029
TI  - Relationship between transferrin saturation and iron stores in the African
      American and US Caucasian populations: analysis of data from the third National
      Health and Nutrition Examination Survey.
AB  - In previous analyses of transferrin saturation data in African Americans and
      Caucasians from the second National Health and Nutrition Examination Survey
      (NHANES II), subpopulations were found consistent with population genetics for
      common loci that influence iron metabolism. The goal of this new study was to
      determine if these transferrin saturation subpopulations have different levels of
      iron stores. Statistical mixture modeling was applied to transferrin saturation
      data for African Americans and Caucasians from the third National Health and
      Nutrition Examination Survey (NHANES III), and then the mean serum ferritin
      concentrations were determined for the transferrin saturation subpopulations that
      were identified. After adjustment for diurnal variation, 3 subpopulations of
      transferrin saturation were identified in each racial group. Satisfying Hardy
      Weinberg conditions for major locus effects, in both racial groups the sum of the
      square roots of the proportion with the lowest mean transferrin saturation and
      the proportion with the highest mean transferrin saturation was approximately 1.
      When weighted to reflect the US adult population as a whole, these subpopulations
      of increasing transferrin saturations had progressively increasing mean age
      adjusted serum ferritin concentration values in each ethnic grouping as
      stratified by sex (trend test, P <.002 for all). These results are consistent
      with the concept that population transferrin saturation subpopulations reflect
      different levels of storage iron.

PMID- 11588028
TI  - Changes in AIDS-related lymphoma since the era of highly active antiretroviral
      therapy.
AB  - HIV infection is associated with a high incidence of AIDS-related lymphomas
      (ARLs). Since the use of highly active antiretroviral therapy (HAART), the
      incidence of AIDS-defining illnesses has decreased, leading to a significant
      improvement in survival of HIV-infected patients. The consequences of HAART use
      on ARL are under debate. This study compared the incidence and the
      characteristics of ARL before and after the use of HAART in a large population of
      HIV-infected patients in the French Hospital Database on HIV (FHDH) and
      particularly in 3 centers including 145 patients with proven lymphoma. Within the
      FHDH, the incidence of systemic ARL has decreased between 1993-1994 and 1997
      1998, from 86.0 per 10 000 to 42.9 per 10 000 person-years (P < 10(-30)). The
      incidence of primary brain lymphoma has also fallen dramatically between the
      periods, from 27.8 per 10 000 to 9.7 per 10 000 person-years (P < 10(-11)). The
      analysis of 145 cases of ARL in 3 hospitals showed that known HIV history was
      longer in the second period than in the first period among patients with systemic
      ARL (98 versus 75 months; P <.01). Patients had a higher number of CD4 cells at
      diagnosis during the second period (191 versus 63/microL, P = 10(-3)). Survival
      of patients with systemic ARL also increased between the periods (from 6 to 20
      months; P =.004). Therefore, the profile of ARL has changed since the era of
      HAART, with a lower incidence of systemic and brain ARL. The prognosis of
      systemic ARL has improved.

PMID- 11588030
TI  - Allogeneic transplantation of CD34(+) selected cells from peripheral blood from
      human leukocyte antigen-identical siblings: detrimental effect of a high number
      of donor CD34(+) cells?
AB  - Clinical results after T-cell-depleted allografts might be improved by modifying
      the graft content of progenitor and accessory cells. Although the association of
      the number of donor T cells with the clinical outcome has been studied
      extensively, the optimum number of progenitor cells that should be administered
      to patients is unknown. The characteristics of 84 consecutive human leukocyte
      antigen (HLA)-identical sibling transplants of granulocyte colony-stimulating
      factor (G-CSF)-mobilized peripheral blood progenitor cells depleted of T cells by
      CD34(+) positive selection (allo-PBT/CD34(+)) were analyzed for their effect on
      clinical outcome. After a median follow-up of 24 months (range, 1-70 months), 50
      patients remain alive (59.5%) and 34 have died (21 [25%] as a result of the
      transplant and 13 [15.5%] due to disease relapse). The median number of CD34(+)
      cells administered to the patients was 3.9 x 10(6)/kg (range, 1.2-14.3 x
      10(6)/kg). A number of CD34(+) cells in the inoculum of 1 x 10(6)/kg to 3 x
      10(6)/kg was associated with increased survival: 21 of 28 (75%) patients are
      alive, as compared with 29 of 56 (52%) patients receiving more than 3 x 10(6)/kg
      (actuarial probability 75% vs. 42%, respectively; P =.01). In the multivariate
      analysis, the independent prognostic variables for survival were CD34(+) cell
      dose 1 x 10(6)/kg to 3 x 10(6)/kg (RR = 4.8; P =.0008), sex-pairing match (RR =
      3.2; P =.002), and early stage of disease (RR = 2.8; P =.007). From these results
      it appears that, in allo-PBT/CD34(+) from HLA-identical siblings, a number of
      CD34(+) cells in the inoculum between 1 x 10(6)/kg to 3 x 10(6)/kg is an
      important factor for better survival, and that higher CD34(+) cell doses might be
      associated with a poorer outcome.

PMID- 11588032
TI  - Integrated src kinase and costimulatory activity enhances signal transduction
      through single-chain chimeric receptors in T lymphocytes.
AB  - Adoptive immunotherapy using receptor-modified T lymphocytes has shown promise in
      preclinical studies for the treatment of infectious and malignant diseases. These
      modified T cells express chimeric receptors that link ligand recognition and
      signal transduction domains in a single gene product. Typically, a single chain
      Fv fragment is genetically attached to the cytoplasmic domain of the T-cell
      receptor (TCR) zeta chain. Modulating the signaling characteristics of chimeric
      receptors will be important for their application to human immunotherapy. It was
      hypothesized that linking coreceptor and costimulatory signaling motifs together
      with the zeta signaling domain will enhance receptor function. The present study
      compares signaling characteristics of 9 single-chain receptors consisting of the
      H-2K(b) extracellular and transmembrane domains and various combinations of T
      cell signal transduction domains. Signal transduction regions studied include the
      TCR zeta chain, the CD4 coreceptor, the lck protein tyrosine kinase, and the CD28
      costimulatory receptor. Biochemical characteristics of the receptors, analyzed
      using calcium flux, receptor, and ZAP-70 phosphorylation, and lck association may
      be predicted from the known functions of receptor constituents. The combination
      of zeta together with coreceptor and costimulatory function in a single receptor
      maximizes chimeric receptor sensitivity and potency. Combining zeta with either
      the costimulatory or coreceptor function independently also enhances receptor
      function, though to a lesser extent. It is therefore possible to link TCR,
      coreceptor, and costimulatory activities in a single functional entity using
      modular domains. Such receptors demonstrate distinct signaling properties and
      should prove useful in the development of chimeric receptors for therapeutic
      purposes.

PMID- 11588031
TI  - Clinical, immunologic, and pathologic correlates of bone marrow involvement in
      291 patients with acquired immunodeficiency syndrome-related lymphoma.
AB  - Bone marrow involvement is reported in approximately 25% of patients with newly
      diagnosed acquired immunodeficiency syndrome-related lymphoma (ARL). Studied were
      291 patients with ARL, diagnosed and treated at one medical center between 1984
      and 1998. Clinical, immunologic, and pathologic characteristics of patients with
      bone marrow involvement were compared with those of patients without marrow
      involvement. Bone marrow involvement was present in 55 patients (19%). Small
      noncleaved lymphoma was diagnosed in 38% of the entire group and was the most
      common pathologic subtype in patients with bone marrow involvement (55% versus
      34%; P =.008). Analysis of complete blood counts revealed a median hemoglobin
      level of 10.6 g/dL in both marrow-positive and marrow-negative groups. In
      contrast, a platelet count lower than 100 000/microL was more common in patients
      with bone marrow involvement (27% versus 11%; P =.02). Patients with marrow
      involvement were more likely to have leptomeningeal (cerebrospinal fluid [CSF])
      lymphoma than patients whose marrows were uninvolved (24% versus 7%; P <.001) and
      were also more likely to have high lactate dehydrogenase (LDH) (P =.002), bone
      involvement (P <.001), and/or systemic B symptoms including fever, night sweats,
      and/or weight loss (P =.05). Median survival did not differ between marrow
      positive and marrow-negative groups. On multivariate analysis, factors associated
      with decreased survival of marrow-positive patients included greater than 50%
      involvement (P =.002), systemic B symptoms (P =.008), and high-grade histologic
      type (P =.035). Marrow involvement in ARL correlates with small noncleaved
      pathology, thrombocytopenia lower than 100 000 mm(3), high LDH, and lymphomatous
      involvement of the CSF. Survival is statistically shorter in patients with
      greater than 50% marrow involvement, high-grade pathology, and/or systemic B
      symptoms.

PMID- 11588033
TI  - Alterations of the phosphoinositide 3-kinase and mitogen-activated protein kinase
      signaling pathways in the erythropoietin-independent Spi-1/PU.1 transgenic
      proerythroblasts.
AB  - During the cell transformation processes leading to erythroleukemia, erythroid
      progenitors often become erythropoietin (Epo)-independent for their
      proliferation. The biochemical events that could lead an erythroleukemic cell to
      growth factor-independence were investigated using spi-1 transgenic
      poerythroblasts. Spi-1/PU.1 is a myeloid and B-cell transcription factor of the
      ETS family and is activated by insertional mutagenesis during Friend
      erythroleukemia. Its overexpression in proerythroblasts induces their
      differentiation arrest without altering their erythropoietin requirement for
      proliferation (HS1 cells). At a later step, genetic alterations most probably
      occur allowing spi-1 transgenic poerythroblasts to proliferate in the absence of
      erythropoietin (HS2 cells). The signaling transduction pathways in HS1 and HS2
      proerythroblasts were analyzed. The authors have previously shown that the
      Jak/STAT pathway was not activated in Epo-independent cells, but remained
      sensitive to Epo stimulation. In the present study, it is shown that the Epo
      independent proliferation of HS2 cells requires active phosphoinositide 3-kinase
      (PI3K) and mitogen-activated protein kinase (MAPK) pathways. In these cells, PI3K
      was constitutively associated with the molecular adapters Grb2 and Gab1, and with
      the phosphatases SHP-2 and SHIP. Moreover, PI3K activity was correlated with the
      constitutive phosphorylation of serine-threonine protein kinase (AKT) in HS2
      cells. Lastly, a constitutive activation of the MAPKs extracellular signal
      regulated kinases (ERK1/2) in HS2 cells was observed that occurs in a PI3K
      independent manner, but depends strictly on the activity of the protein kinase C
      (PKC). These results suggest that constitutive activations of PI3K/AKT and
      PKC/MAPK pathways can act in synergy to lead a proerythroblast to proliferate
      without Epo.

PMID- 11588034
TI  - Multipotent hematopoietic cell lines derived from C/EBPalpha(-/-) knockout mice
      display granulocyte macrophage-colony-stimulating factor, granulocyte- colony
      stimulating factor, and retinoic acid-induced granulocytic differentiation.
AB  - The transcription factor C/EBPalpha is an important mediator of granulocyte
      differentiation and regulates the expression of multiple granulocyte-specific
      genes including the granulocyte-colony-stimulating factor (G-CSF) receptor,
      neutrophil elastase, and myeloperoxidase. Indeed C/EBPalpha knockout mice display
      a profound block in granulocyte differentiation. To study this block in
      granulocytic differentiation in more detail, retroviral vector-mediated
      transduction of a dominant-negative retinoic acid receptor was used to establish
      hematopoietic growth factor-dependent, lympho-myeloid progenitor cell lines from
      the fetal livers of both the C/EBPalpha knockout animals (C/EBPalpha(-/-)) and
      their heterozygous littermates (C/EBPalpha(+/-)). Surprisingly, the C/EBPalpha(-/
      ) cell lines displayed significant spontaneous granulocytic differentiation, and
      this differentiation was markedly enhanced when the cells were stimulated with
      granulocyte macrophage (GM)-CSF. This GM-CSF-mediated differentiation was
      associated with the up-regulation of G-CSF receptor mRNA, and the combination of
      GM-CSF and G-CSF generated more than 95% mature neutrophils in the C/EBPalpha(-/
      ) cultures. The addition of all-trans retinoic acid also enhanced this
      granulocytic differentiation of the cultured C/EBPalpha(-/-) cells, indicating
      that the activated retinoic acid receptors can enhance granulocytic
      differentiation through a molecular pathway that is independent of C/EBPalpha.
      These studies clearly indicate that terminal granulocytic differentiation
      associated with the up-regulation of C/EBPalpha-responsive genes can occur in the
      absence of C/EBPalpha, and they indicate the existence of multiple independent
      molecular pathways potentially used by primitive hematopoietic precursors that
      can lead to the development of mature granulocytes.

PMID- 11588035
TI  - Roles of tumor necrosis factor-alpha receptor subtypes in the pathogenesis of the
      tristetraprolin-deficiency syndrome.
AB  - Tristetraprolin (TTP) is a member of the CCCH tandem zinc-finger class of
      proteins. It can bind to and destabilize mRNAs encoding tumor necrosis factor
      alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF).
      Conversely, mice deficient in TTP develop a complex syndrome characterized by
      cachexia, myeloid hyperplasia, and joint and skin inflammation. Studies using
      anti-TNF-alpha neutralizing antibodies demonstrated that this syndrome, at least
      in part, is a consequence of the excess production of TNF-alpha in the absence of
      TTP. To evaluate the role played by each TNF-alpha receptor in the pathogenesis
      of this syndrome, mice were generated that were deficient in TTP and either or
      both of the known TNF-alpha receptors (TNFRs), type 1 (TNFR1) and type 2 (TNFR2).
      Mice deficient in TTP and TNFR1, or in TTP and both receptors, were protected
      from developing the TNF-alpha-induced cachexia and inflammation. In contrast,
      mice deficient in TNFR2 were more severely affected than mice deficient in TTP
      alone, suggesting that TNFR2 might play a protective role in the development of
      the syndrome. In cultured cells derived from these mice, apparent cooperation
      between the TNFRs was required to achieve normal TNF-alpha-induced expression of
      TTP, TNF-alpha, and GM-CSF mRNAs. Finally, the results showed that TNFR1 plays an
      important role in mediating TNF-alpha-induced changes in TNF-alpha and GM-CSF
      mRNA stability.

PMID- 11588036
TI  - Identification of mesenchymal stem/progenitor cells in human first-trimester
      fetal blood, liver, and bone marrow.
AB  - Human mesenchymal stem/progenitor cells (MSCs) have been identified in adult bone
      marrow, but little is known about their presence during fetal life. MSCs were
      isolated and characterized in first-trimester fetal blood, liver, and bone
      marrow. When 10(6) fetal blood nucleated cells (median gestational age, 10(+2)
      weeks [10 weeks, 2 days]) were cultured in 10% fetal bovine serum, the mean
      number (+/- SEM) of adherent fibroblastlike colonies was 8.2 +/- 0.6/10(6)
      nucleated cells (69.6 +/- 10/microL fetal blood). Frequency declined with
      advancing gestation. Fetal blood MSCs could be expanded for at least 20 passages
      with a mean cumulative population doubling of 50.3 +/- 4.5. In their
      undifferentiated state, fetal blood MSCs were CD29(+), CD44(+), SH2(+), SH3(+),
      and SH4(+); produced prolyl-4-hydroxylase, alpha-smooth muscle actin,
      fibronectin, laminin, and vimentin; and were CD45(-), CD34(-), CD14(-), CD68(-),
      vWF(-), and HLA-DR(-). Fetal blood MSCs cultured in adipogenic, osteogenic, or
      chondrogenic media differentiated, respectively, into adipocytes, osteocytes, and
      chondrocytes. Fetal blood MSCs supported the proliferation and differentiation of
      cord blood CD34(+) cells in long-term culture. MSCs were also detected in first
      trimester fetal liver (11.3 +/- 2.0/10(6) nucleated cells) and bone marrow (12.6
      +/- 3.6/10(6) nucleated cells). Their morphology, growth kinetics, and
      immunophenotype were comparable to those of fetal blood-derived MSCs and
      similarly differentiated along adipogenic, osteogenic, and chondrogenic lineages,
      even after sorting and expansion of a single mesenchymal cell. MSCs similar to
      those derived from adult bone marrow, fetal liver, and fetal bone marrow
      circulate in first-trimester human blood and may provide novel targets for in
      utero cellular and gene therapy.

PMID- 11588037
TI  - Molecular pathways in bone marrow homing: dominant role of alpha(4)beta(1) over
      beta(2)-integrins and selectins.
AB  - The specific retention of intravenously administered hemopoietic cells within
      bone marrow is a complex multistep process. Despite recent insights, the
      molecular mechanics governing this process remain largely undefined. This study
      explored the influence of beta(2)-integrins on the homing to bone marrow and
      repopulation kinetics of progenitor cells. Both antifunctional antibodies and
      genetically deficient cells were used. In addition, triple selectin-deficient
      mice were used as recipients of either deficient (selectin or beta(2)) or normal
      cells in homing experiments. The homing patterns of either beta(2) null or
      selectin null cells into normal or selectin-deficient recipients were similar to
      those of normal cells given to normal recipients. Furthermore, spleen colony
      forming units and the early bone marrow repopulating activity for the first 2
      weeks after transplantation were not significantly different from those of
      control cells. These data are in contrast to the importance of beta(2)-integrin
      and selectins in the adhesion/migration cascade of mature leukocytes. The special
      bone marrow flow hemodynamics may account for these differences. Although early
      deaths after transplantation can be seen in recipients deficient in CD18 and
      selectin, these are attributed to septic complications rather than homing
      defects. However, when beta(2)- or selectin-null donor cells are treated with
      anti-alpha(4) antibodies before their transplantation to normal or selectin
      deficient recipients, a dramatic inhibition of homing (>90%) was found. The data
      suggest that the alpha(4)beta(1)/vascular cell adhesion molecule-1 pathway alone
      is capable of providing effective capture of cells within the bone marrow, but if
      its function is compromised, the synergistic contribution of other pathways, that
      is, beta(2)-integrins or selectins, is uncovered.

PMID- 11588038
TI  - Identification of a candidate human neurohematopoietic stem-cell population.
AB  - It was recently reported that transplantation of clonally derived murine
      neurosphere cells into sublethally irradiated allogeneic hosts leads to a donor
      derived hematopoietic reconstitution. The confirmation of the existence of a
      common neurohematopoietic stem cell in the human brain will have a significant
      effect on stem cell research and on clinical transplantation. Here, it is
      demonstrated that the human fetal brain contains separate but overlapping
      epidermal growth factor (EGF)-responsive and basic fibroblast growth factor (FGF
      2)-responsive neural stem cells. The majority (> 85%) of cells within these EGF-
      and/or FGF-2-generated neurospheres express characteristic neural stem/progenitor
      cell markers including nestin, EGF receptor, and FGF-2 receptor. These neural
      stem cells can be continuously passaged in vitro, and demonstrate a constant 20
      fold expansion in every passage for up to the fifth passage (the longest period
      that has been carried out in the authors' laboratory). These neural stem cells
      are multipotential for neurons, astrocytes, and oligodendrocytes. After
      transplantation into SCID-hu mice, all neural stem cells, regardless of passages,
      culture conditions, and donors, are able to establish long-term hematopoietic
      reconstitution in the presence of an intact human bone marrow microenvironment.

PMID- 11588039
TI  - Blood coagulation at the site of microvascular injury: effects of low-dose
      aspirin.
AB  - The sequence of coagulant reactions in vivo following vascular injury is poorly
      characterized. Using quantitative immunoassays, the time courses were evaluated
      for activation of prothrombin, factor (F)V, FXIII, fibrinogen (Fbg) cleavage, and
      FVa inactivation in bleeding-time blood collected at 30-second intervals from 12
      healthy subjects both before and after aspirin ingestion. Prothrombin decreased
      at a maximum rate of 14.2 +/- 0.6 nM per second to 10% of initial values at the
      end of bleeding. Significant amounts of alpha-thrombin B chain appeared rapidly
      at 90 seconds of bleeding and increased at a maximum rate of 0.224 +/- 0.03 nM
      per second to a peak value of 38 nM. Kinetics of prethrombin 2 generation was
      almost identical. Prothrombinase concentration reached a peak value of 22 pM at
      150 seconds and then decreased to 9 pM at the end of bleeding. Prothrombin
      fragment 1.2 (F1.2) was produced explosively (0.673 +/- 0.05 nM per second),
      whereas thrombin-antithrombin III (TAT) complexes were generated at a much slower
      rate (0.11 +/- 0.008 nM per second; P =.002). FVa light chain was detectable 30
      seconds later than the heavy chain (150 seconds) and was produced at a slightly
      slower rate (0.027 +/- 0.001 nM per second) when compared with the heavy chain
      (0.032 +/- 0.002 nM per second; P =.041). The 30 000 fragment (residues 307-506)
      of FVa heavy chain produced by activated protein C appeared as early as at 90
      seconds and increased with time. Fbg was removed from the blood shed with a high
      rate of 0.047 +/- 0.02 microM/s and became undetectable at approximately 180
      seconds of bleeding. The velocity of FXIII activation correlated with thrombin B
      chain formation. A 7-day aspirin administration (75 mg/d) resulted in significant
      reductions in maximum rates of (1) prothrombin removal (by 29%; P =.008);
      generation of alpha-thrombin B-chain (by 27.2%; P =.022), and prethrombin 2 (by
      26%; P =.014); formation of F1.2 (by 31.4%; P =.009) and TAT (by 30.3%; P =
      0.013); (2) release of FVa heavy chain (by 25%; P =.003) and FVa light chain (by
      29.6%; P =.007); (3) Fbg depletion from solution (by 30.5%; P =.002); and (4)
      FXIII activation (by 28.6%; P =.003). Total amounts of the proteins studied,
      collected at every interval, also significantly decreased following aspirin
      ingestion. These results indicate that low-dose aspirin impairs thrombin
      generation and reactions catalyzed by this enzyme at the site of the injury.

PMID- 11588040
TI  - A point mutation in the cysteine-rich domain of glycoprotein (GP) IIIa results in
      the expression of a GPIIb-IIIa (alphaIIbbeta3) integrin receptor locked in a high
      affinity state and a Glanzmann thrombasthenia-like phenotype.
AB  - This article reports a Glanzmann thrombasthenia (GT) patient, N.M., with a point
      mutation in the third cysteine-rich repeat of beta3-integrin or platelet
      glycoprotein (GP) IIIa, leading to the expression of a constitutively activated
      fibrinogen receptor. The diagnosis of GT was based on a severely reduced platelet
      aggregation response to a series of agonists and approximately 20% of surface
      expressed GPIIb-IIIa. The patient's GPIIb-IIIa constitutively expressed epitopes
      recognized by antibodies to ligand-induced binding sites (LIBS) and also
      spontaneously bound the fibrinogen-mimetic antibody, PAC-1. Furthermore,
      significant amounts of bound fibrinogen were detected on his platelets ex vivo.
      No signs of platelet activation were observed on sections of unstimulated
      platelets from N.M. by electron microscopy. Immunogold labeling highlighted the
      presence of surface-bound fibrinogen but revealed platelet heterogeneity with
      regard to the surface density. When the patient's platelets were stimulated by
      thrombin-receptor activating peptide, amounts of surface-expressed GPIIb-IIIa
      increased and the aggregation response improved, although it failed to normalize.
      Platelets from N.M. were able to adhere and spread on immobilized fibrinogen.
      Sequence analysis of genomic DNA from N.M. revealed a homozygous g1776T>C
      mutation in GPIIIa, leading to a Cys560Arg amino acid substitution. A stable
      Chinese hamster ovary (CHO) cell line was prepared expressing surface GPIIb
      Arg560IIIa. Like platelets from the patient, GPIIb-Arg560IIIa-transfected CHO
      cells constitutively bound LIBS antibodies and PAC-1. They also showed an
      enhanced ability to adhere on surface-bound fibrinogen. Overall, these data
      demonstrate that a gain-of-function mutation can still be associated with a
      thrombasthenic phenotype even though platelets show spontaneous fibrinogen
      binding.

PMID- 11588041
TI  - Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires
      human platelet factor 4 and platelet activation through FcgammaRIIA.
AB  - Heparin-induced thrombocytopenia/thrombosis (HIT/HITT) is a severe, life
      threatening complication that occurs in 1% to 3% of patients exposed to heparin.
      Interactions between heparin, human platelet factor 4 (hPF4), antibodies to the
      hPF4/heparin complex, and the platelet Fc receptor (FcR) for immunoglobulin G,
      FcgammaRIIA, are the proposed primary determinants of the disease on the basis of
      in vitro studies. The goal of this study was to create a mouse model that
      recapitulates the disease process in humans in order to understand the factors
      that predispose some patients to develop thrombocytopenia and thrombosis and to
      investigate new therapeutic approaches. Mice that express both human platelet
      FcgammaRIIA and hPF4 were generated. The FcgammaRIIA/hPF4 mice and controls,
      transgenic for either FcgammaRIIA or hPF4, were injected with KKO, a mouse
      monoclonal antibody specific for hPF4/heparin complexes, and then received
      heparin (20 U/d). Nadir platelet counts for KKO/heparin-treated FcgammaRIIA/hPF4
      mice were 80% below baseline values, significantly different (P <.001) from
      similarly treated controls. FcgammaRIIA/hPF4 mice injected with KKO and 50 U/d
      heparin developed shock and showed fibrin-rich thrombi in multiple organs,
      including thrombosis in the pulmonary vasculature. This is the first mouse model
      of HIT to recapitulate the salient features of the human disease and demonstrates
      that FcgammaRIIA and hPF4 are both necessary and sufficient to replicate HIT/HITT
      in an animal model. This model should facilitate the identification of factors
      that modulate disease expression and the testing of novel therapeutic
      interventions.

PMID- 11588042
TI  - The alternatively spliced alpha(E)C domain of human fibrinogen-420 is a novel
      ligand for leukocyte integrins alpha(M)beta(2) and alpha(X)beta(2).
AB  - The interaction of human plasma fibrinogen with leukocyte integrins
      alpha(M)beta(2) (CD11b/CD18, Mac-1) and alpha(X)beta(2) (CD11c/CD18, p150,95) is
      an important component of the inflammatory response. Previously, it was
      demonstrated that binding of fibrinogen to these integrins is mediated by gammaC,
      the globular C-terminal domain of the gamma chain. In this study, evidence was
      found of another fibrinogen domain that can serve as a ligand for the 2 leukocyte
      integrins: alpha(E)C, a homologous domain that extends the alpha chains in a
      recently discovered subclass of fibrinogen known as fibrinogen-420. Recombinant
      alpha(E)C supported strong adhesion and migration of cells expressing
      alpha(M)beta(2) and alpha(X)beta(2), including nonactivated and activated U937
      and THP-1 monocytoid cells, and neutrophils. Cells transfected with complementary
      DNA for these integrins also bound alpha(E)C. The specificity of interaction was
      substantiated by inhibition of cell adhesion with antibodies against alpha(M),
      alpha(X), and beta(2) subunits. Also, neutrophil inhibitory factor, a specific
      inhibitor of alpha(M)beta(2) and alpha(X)beta(2) function, efficiently blocked
      cell adhesion to alpha(E)C. In alpha(M)beta(2) and alpha(X)beta(2), the I domain
      is the binding site for alpha(E)C, since alpha(E)C bound to recombinant alpha(M)
      I and alpha(X)I domains in a dose-dependent and saturable manner. Synthetic
      peptides that duplicated sequences gamma190 to 202 and gamma377 to 395,
      previously considered putative binding sites in gammaC, effectively inhibited
      alpha(M)beta(2)- and alpha(X)beta(2)-mediated adhesion to alpha(E)C, suggesting
      that recognition of alpha(E)C by the I domain involves structural features in
      common with those of gammaC. These findings identify alpha(E)C as a second domain
      in fibrinogen-420 that binds alpha(M)beta(2) and alpha(X)beta(2) and can mediate
      leukocyte adhesion and migration.

PMID- 11588043
TI  - Basic helix-loop-helix proteins E2A and HEB induce immature T-cell receptor
      rearrangements in nonlymphoid cells.
AB  - T-cell receptor (TCR) gene rearrangements are mediated via V(D)J recombination,
      which is strictly regulated during lymphoid differentiation, most probably
      through the action of specific transcription factors. Investigated was whether
      cotransfection of RAG1 and RAG2 genes in combination with lymphoid transcription
      factors can induce TCR gene rearrangements in nonlymphoid human cells.
      Transfection experiments showed that basic helix-loop-helix transcription factors
      E2A and HEB induce rearrangements in the TCRD locus (Ddelta2-Ddelta3 and Vdelta2
      Ddelta3) and TCRG locus (psi Vgamma7-Jgamma2.3 and Vgamma8-Jgamma2.3). Analysis
      of these rearrangements and their circular excision products revealed some
      peculiar characteristics. The Vdelta2-Ddelta3 rearrangements were formed by
      direct coupling without intermediate Ddelta2 gene segment usage, and most Ddelta2
      Ddelta3 recombinations occurred via direct coupling of the respective upstream
      and downstream recombination signal sequences (RSSs) with deletion of the Ddelta2
      and Ddelta3 coding sequences. Subsequently, the E2A/HEB-induced TCR gene
      recombination patterns were compared with those in early thymocytes and acute
      lymphoblastic leukemias of T- and B-lineage origin, and it was found that the TCR
      rearrangements in the transfectants were early (immature) and not necessarily T
      lineage specific. Apparently, some parts of the TCRD (Vdelta2-Ddelta region) and
      TCRG genes are accessible for recombination not only in T cells, but also in
      early B-cells and even in nonlymphoid cells if the appropriate transcription
      factors are present. The transfection system described here appeared to be useful
      for studying the accessibility of immunoglobulin and TCR genes for V(D)J
      recombination, but might also be applied to study the induction of RSS-mediated
      chromosome aberrations.

PMID- 11588044
TI  - Immunophenotypic profiles in families with autoimmune lymphoproliferative
      syndrome.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) type Ia is caused by inherited
      defects in apoptosis and is characterized by nonmalignant lymphoaccumulation,
      autoimmunity, and increased alpha/beta(+) double-negative T cells (alpha/beta(+)
      DNT cells). This study reports immunophenotypic findings in 166 members of 31
      families with ALPS type Ia, associated with genetic mutations in the TNFRSF6 gene
      encoding Fas. The ALPS type Ia probands (n = 31) and relatives having both a Fas
      mutation and clinically proven ALPS (n = 28) showed significant expansion of
      CD8(+) T cells, alpha/beta(+)-DNT cells, gamma/delta(+)-DNT cells, CD3(+)/ HLA
      DR(+) T cells, CD8(+)/CD57(+) T cells, and CD5(+) B cells. Relatives with Fas
      mutations, but without all the required criteria for ALPS (n = 42), had
      expansions of CD8(+) T cells, alpha/beta(+)-DNT cells, and gamma/delta(+)-DNT
      cells. Interestingly, relatives without a Fas mutation and with no features of
      ALPS (n = 65) demonstrated a small but significant expansion of CD8(+) T cells,
      both DNT cell subsets, and CD5(+) B cells. As compared to unrelated healthy
      controls, lymphocyte subset alterations were greatest in the probands, followed
      by the relatives with mutations and ALPS. Probands and relatives with mutations
      and ALPS also showed a lower number of CD4(+)/CD25(+) T cells that, in
      combination with an independent increase in HLA-DR(+) T cells, provided a profile
      predictive of the presence of clinical ALPS. Because quantitative defects in
      apoptosis were similar in mutation-positive relatives regardless of the presence
      of clinical ALPS, factors, other than modifiers of the Fas apoptosis pathway,
      leading to these distinctive immunophenotypic profiles most likely contribute to
      disease penetrance in ALPS.

PMID- 11588045
TI  - Human herpesvirus 7 induces the functional up-regulation of tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) coupled to TRAIL-R1 down-modulation in
      CD4(+) T cells.
AB  - Human herpesvirus 7 (HHV-7) is endemic in the adult human population. Although
      HHV-7 preferentially infects activated CD4(+) T lymphocytes, the consequence of T
      cell infection for viral pathogenesis and immunity are still largely unknown. HHV
      7 infection induces apoptosis mostly in uninfected bystander cells but not in
      productively infected CD4(+) T cells. To dissect the underlying molecular events,
      the role of death-inducing ligands belonging to the tumor necrosis factor (TNF)
      cytokine superfamily was investigated. HHV-7 selectively up-regulated the
      expression of TNF-related apoptosis-inducing ligand (TRAIL), but not that of CD95
      ligand or TNF-alpha in lymphoblastoid (SupT1) or primary activated CD4(+) T
      cells. Moreover, in a cell-to-cell-contact assay, HHV-7-infected CD4(+) T
      lymphocytes were cytotoxic for bystander uninfected CD4(+) T cells through the
      TRAIL pathway. By contrast, HHV-7 infection caused a marked decrease of surface
      TRAIL-R1, but not of TRAIL-R2, CD95, TNF-R1, or TNF-R2. Of note, the down
      regulation of TRAIL-R1 selectively occurred in cells coexpressing HHV-7 antigens
      that became resistant to TRAIL-mediated cytotoxicity. These findings suggest that
      the TRAIL-mediated induction of T-cell death may represent an important immune
      evasion mechanism of HHV-7, helping the virus to persist in the host organism
      throughout its lifetime.

PMID- 11588046
TI  - HIV gp120 receptors on human dendritic cells.
AB  - Dendritic cells (DCs) are important targets for human immunodeficiency virus
      (HIV) because of their roles during transmission and also maintenance of immune
      competence. Furthermore, DCs are a key cell in the development of HIV vaccines.
      In both these settings the mechanism of binding of the HIV envelope protein gp120
      to DCs is of importance. Recently a single C-type lectin receptor (CLR), DC-SIGN,
      has been reported to be the predominant receptor on monocyte-derived DCs (MDDCs)
      rather than CD4. In this study a novel biotinylated gp120 assay was used to
      determine whether CLR or CD4 were predominant receptors on MDDCs and ex vivo
      blood DCs. CLR bound more than 80% of gp120 on MDDCs, with residual binding
      attributable to CD4, reconfirming that CLRs were the major receptors for gp120 on
      MDDCs. However, in contrast to recent reports, gp120 binding to at least 3 CLRs
      was observed: DC-SIGN, mannose receptor, and unidentified trypsin resistant
      CLR(s). In marked contrast, freshly isolated and cultured CD11c(+ve) and CD11c(
      ve) blood DCs only bound gp120 via CD4. In view of these marked differences
      between MDDCs and blood DCs, HIV capture by DCs and transfer mechanisms to T
      cells as well as potential antigenic processing pathways will need to be
      determined for each DC phenotype.

PMID- 11588048
TI  - Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662
      consecutive bone marrow specimens by 4-color flow cytometry.
AB  - Bone marrow hematogones (B-lymphocyte precursors) may cause problems in diagnosis
      because of their morphologic and immunophenotypic similarities to neoplastic
      lymphoblasts. The purposes of this prospective, multiparametric flow cytometry
      study were to quantify hematogones across age groups and a spectrum of clinical
      conditions, to identify factors that affect the relative quantity of hematogones,
      and to compare their immunophenotype with that of neoplastic lymphoblasts. A
      total of 662 consecutive marrow specimens were analyzed for hematogones using one
      of two 4-color antibody combinations; hematogones were identified in 528 (79.8%).
      There was a significant decline in hematogones with increasing age (P <.001), but
      a broad range was found at all ages and many adults had a relatively high number.
      Specimens processed by density gradient had a higher mean percent hematogones
      than those processed by erythrocyte lysis (P <.001). There was a direct decline
      in hematogones with increasing marrow involvement with neoplastic cells. A total
      of 8% of the 662 specimens contained 5% or more hematogones: 24.6% of specimens
      from patients aged less than 16 years and 6.3% from those 16 and older (P <.000
      01). Increased hematogones were observed most often in patients with lymphoma,
      marrow regenerative states, immune cytopenias, and acquired immunodeficiency
      syndrome. Hematogones always exhibited a typical complex spectrum of antigen
      expression that defines the normal antigenic evolution of B-cell precursors and
      lacked aberrant expression. In contrast, lymphoblasts in 49 cases of precursor B
      ALL showed maturation arrest and exhibited 1 to 11 immunophenotypic aberrancies.
      Four-color flow cytometry with optimal combinations of antibodies consistently
      distinguishes between hematogones and neoplastic lymphoblasts.

PMID- 11588047
TI  - Calcium signaling inhibits interleukin-12 production and activates CD83(+)
      dendritic cells that induce Th2 cell development.
AB  - Mature dendritic cells (DCs), in addition to providing costimulation, can define
      the Th1, in contrast to the Th2, nature of a T-cell response through the
      production of cytokines and chemokines. Because calcium signaling alone causes
      rapid DC maturation of both normal and transformed myeloid cells, it was
      evaluated whether calcium-mobilized DCs polarize T cells toward a Th1 or a Th2
      phenotype. After human monocytes were cultured for 24 hours in serum-free medium
      and granulocyte-macrophage colony-stimulating factor to produce immature DCs,
      additional overnight culture with either calcium ionophore (CI) or interferon
      gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and soluble CD40L
      resulted in phenotypically mature DCs that produced interleukin-8 (IL-8) and
      displayed marked expression of CD80, CD86, CD40, CD54, CD83, DC-LAMP, and RelB.
      DCs matured by IFN-gamma, TNF-alpha, and soluble CD40L were additionally
      distinguished by undetectable CD4 expression, marked secretion of IL-12, IL-6,
      and MIP-1beta, and preferential ability to promote Th1/Tc1 characteristics during
      T-cell sensitization. In contrast, DCs matured by CI treatment were distinguished
      by CD4 expression, modest or absent levels of IL-12, IL-6, and MIP-1beta, and
      preferential ability to promote Th2/Tc2 characteristics. Calcium signaling
      selectively antagonized IL-12 production by mature DCs activated with IFN-gamma,
      TNF-alpha, and soluble CD40L. Although the activation of DCs by calcium signals
      is largely mediated through calcineurin phosphatase, the inhibition of IL-12
      production by calcium signaling was independent of this enzyme. Naturally
      occurring calcium fluxes in immature DCs, therefore, negatively regulate Dc1
      differentiation while promoting Dc2 characteristics and Th2/Tc2 polarization.
      Calcium-mobilized DCs may have clinical usefulness in treating disease states
      with excessive Th1/Tc1 activity, such as graft-versus-host disease or
      autoimmunity.

PMID- 11588049
TI  - Transformation of interleukin-3-dependent cells without participation of
      Stat5/bcl-xL: cooperation of akt with raf/erk leads to p65 nuclear factor kappaB
      mediated antiapoptosis involving c-IAP2.
AB  - Tyrosine kinase oncogenes such as p210BCR-ABL activate multiple signal pathways.
      As a result, it is difficult to infer the functional relevance of a pathway
      acting alone or in cooperation with another. One or 2 second-tier kinases
      represented in the p21ras and phosphatidylinositol-3-kinase (PI-3-kinase)
      pathways (activated RafCAAX and gag-akt, respectively) were expressed in parental
      H7 interleukin-3 (IL-3)-dependent myeloid cells. IL-3-dependent cells served,
      independently, as recipients of p210BCR-ABL, which activated p21ras and PI-3
      kinase pathways, including raf/erk and akt, respectively, en route to
      transformation. By contrast, neither RafCAAX nor gag-akt when expressed in
      parental cells in isolation produced factor-independent cells. On the other hand,
      H7 cells expressing both RafCAAX and gag-akt (H7gag-akt/RafCAAX) were
      transformed. Such transformation in H7gag-akt/RafCAAX was accomplished in the
      absence of active versions of Shc or cbl, and there was no evidence of Stat
      activity and only modest amounts of bcl-xL, a Stat5 transcriptional target
      protein, all of which characterized the cells transformed by BCR-ABL. However,
      H7gag-akt/RafCAAX cells and H7BCR-ABL cells cultured in the absence of IL-3
      shared strikingly increased p65 nuclear factor kappaB (NFkappaB) activity.
      Treatment of cells with a specific NFkappaB inhibitor, parthenolide, led to loss
      of NFkappaB activity and down-regulation of antiapoptotic c-IAP2. In cells with
      only gag-akt/RafCAAX, this was sufficient to allow polyADP ribosyltransferase
      (PARP)-degradative apoptosis, but in cells with p210BCR-ABL, apoptosis was
      blocked, possibly by a Stat5/bcl-xL-dependent mechanism. Therefore, one
      hematopoietic antiapoptotic program, among others, available to certain tyrosine
      kinase oncogenes involves a cooperative response between raf/erk and akt,
      unambiguous components of p21ras and PI-3-kinase pathways, to induce p65 NFkappaB
      and c-IAP2.

PMID- 11588050
TI  - Rabaptin-5 is a novel fusion partner to platelet-derived growth factor beta
      receptor in chronic myelomonocytic leukemia.
AB  - Chromosomal translocations involving the platelet-derived growth factor beta
      receptor (PDGFbetaR) gene have been reported in some patients with chronic
      myelomonocytic leukemia (CMML). The resultant fusion proteins have constitutive
      PDGFbetaR tyrosine kinase activity, but the partner genes previously reported
      (tel, Huntingtin interacting protein 1 [HIP-1], H4/D10S170) have poorly
      understood roles in the oncogenic activity of the fusion proteins. A novel
      PDGFbetaR fusion protein has been characterized in a patient with CMML and an
      acquired t(5;17)(q33;p13). Southern blot analysis on patient leukemia cells
      demonstrated involvement of the PDGFbetaR gene. Using 5' rapid amplification of
      complementary DNA ends-polymerase chain reaction (RACE-PCR) on patient RNA,
      rabaptin-5 was identified as a novel partner fused in-frame to the PDGFbetaR
      gene. The new fusion protein includes more than 85% of the native Rabaptin-5
      fused to the transmembrane and intracellular tyrosine kinase domains of the
      PDGFbetaR. Transduction with a retroviral vector expressing rabaptin-5/PDGFbetaR
      transformed the hematopoietic cell line Ba/F3 to growth factor independence and
      caused a fatal myeloproliferative disease in mice. Rabaptin-5 is a well-studied
      protein shown to be an essential and rate-limiting component of early endosomal
      fusion through interaction with the Ras family GTPases Rab5 and Rab4. The fusion
      protein includes 3 of 4 coiled-coil domains (involved in homodimerization of
      native rabaptin-5), 2 caspase-3 cleavage sites, and a binding site for the tumor
      suppressor gene tuberin (tuberous sclerosis complex-2). Early endosomal transport
      is critical in regulation of various growth factor receptors, through ligand
      induced clathrin-mediated endocytosis, and thus this new fusion protein links
      together 2 important pathways of growth regulation.

PMID- 11588051
TI  - Induction of a long-lasting antitumor immunity by a trifunctional bispecific
      antibody.
AB  - Bispecific antibodies (bsAbs) can efficiently mediate tumor cell killing by
      redirecting preactivated or costimulated T cells to disseminated tumor cells,
      especially in a minimal residual disease situation. This study demonstrates that
      the trifunctional bsAb BiLu is able to kill tumor cells very efficiently without
      any additional costimulation of effector cells in vitro and in vivo. Remarkably,
      this bsAb also induces a long-lasting protective immunity against the targeted
      syngeneic mouse tumors (B16 melanoma and A20 B-cell lymphoma, respectively). A
      strong correlation was observed between the induction of a humoral immune
      response with tumor-reactive antibodies and the survival of mice. This humoral
      response was at least in part tumor specific as shown in the A20 model by the
      detection of induced anti-idiotype antibodies. Both the survival of mice and
      antitumor titers were significantly diminished when F(ab')(2) fragments of the
      same bsAb were applied, demonstrating the importance of the Fc region in this
      process. With the use of T-cell depletion, a contribution of a cellular antitumor
      response could be demonstrated. These results reveal the necessity of the Fc
      region of the bsAb with its potent immunoglobulin subclass combination mouse
      immunoglobulin G2a (IgG2a) and rat IgG2b. The antigen-presenting system seems to
      be crucial for achieving an efficient tumor cell killing and induction of long
      lasting antitumor immunity. Hereby, the recruitment and activation of accessory
      cells by the intact bsAb is essential.

PMID- 11588052
TI  - A comparative evaluation of conventional and pretargeted radioimmunotherapy of
      CD20-expressing lymphoma xenografts.
AB  - Radioimmunotherapy with anti-CD20 monoclonal antibodies is a promising new
      treatment approach for patients with relapsed B-cell lymphomas. However, the
      majority of patients treated with conventional radiolabeled anti-CD20 antibodies
      eventually have a relapse because the low tumor-to-blood and tumor-to-normal
      organ ratios of absorbed radioactivity limit the dose that can be safely
      administered without hematopoietic stem cell support. This study assessed the
      ability of a streptavidin-biotin "pretargeting" approach to improve the
      biodistribution of radioactivity in mice bearing Ramos lymphoma xenografts. A
      pretargeted streptavidin-conjugated anti-CD20 1F5 antibody was infused, followed
      24 hours later by a biotinylated N-acetylgalactosamine-containing "clearing
      agent" and finally 3 hours later by (111)In-labeled DOTA-biotin. Tumor-to-blood
      ratios were 3:1 or more with pretargeting, compared with 0.5:1 or less with
      conventional (111)In-1F5. Tumor-to-normal organ ratios of absorbed radioactivity
      up to 56:1 were observed with pretargeting, but were 6:1 or less with
      conventional (111)In-1F5. Therapy experiments demonstrated that 400 microCi (14.8
      MBq) or more of conventional (90)Y-1F5 was required to obtain major tumor
      responses, but this dose was associated with lethal toxicity in 100% of mice. In
      marked contrast, up to 800 microCi (29.6 MBq) (90)Y-DOTA-biotin could be safely
      administered by the pretargeting approach with only minor toxicity, and 89% of
      the mice were cured. These data suggest that anti-CD20 pretargeting shows great
      promise for improving current therapeutic options for B-cell lymphomas and
      warrants further preclinical and clinical testing.

PMID- 11588053
TI  - Bifurcation of osteoclasts and dendritic cells from common progenitors.
AB  - Osteoclasts and dendritic cells are derived from monocyte/macrophage precursor
      cells; however, how their lineage commitment is regulated is unknown. This study
      investigated the differentiation pathways of osteoclasts and dendritic cells from
      common precursor cells at the single-cell level. Osteoclastogenesis induced by
      macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear
      factor-kappaB ligand (RANKL) or tumor necrosis factor-alpha (TNF-alpha) is
      completely inhibited by addition of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) or interleukin-3 at early stages of differentiation. GM-CSF
      treated cells express both c-Fms and RANK and also low levels of CD11c and
      DEC205, which are detected on dendritic cells. Addition of GM-CSF also reduces
      expression of both c-Fos and Fra-1, which is an important event for inhibition of
      osteoclastogenesis. Overexpression of c-Fos by retroviral infection or induction
      in transgenic mice can rescue a failure in osteoclast differentiation even in the
      presence of GM-CSF. By contrast, differentiation into dendritic cells is
      inhibited by M-CSF, indicating that M-CSF and GM-CSF reciprocally regulate the
      differentiation of both lineages. Dendritic cell maturation is also inhibited
      when c-Fos is expressed at an early stage of differentiation. Taken together,
      these findings suggest that c-Fos is a key mediator of the lineage commitment
      between osteoclasts and dendritic cells. The lineage determination of osteoclast
      progenitors seen following GM-CSF treatment functions through the regulation of c
      Fos expression.

PMID- 11588055
TI  - Lineage restriction of the RARalpha gene expression in myeloid differentiation.
AB  - To better understand the role of retinoids in myelopoiesis, expression of the
      retinoid receptor genes (retinoic acid receptors [RARs] and retinoid X receptors
      [RXRs]) were examined during differentiation of factor-dependent cell-Paterson
      (FDCP)-mixA4 murine progenitor cells. The major receptor expressed in
      undifferentiated A4 cells was RARalpha (primarily the RARalpha1 isoform).
      Following induction of myelomonocytic differentiation with granulocyte and
      granulocyte-macrophage colony-stimulating factors, a dramatic increase in
      RARalpha expression (particularly the RARalpha2 isoform) was seen. In contrast,
      expression of both RARalpha isoforms was rapidly extinguished upon induction of
      erythroid differentiation with erythropoeitin (EPO). A modest induction of
      RXRalpha expression was seen, particularly during differentiation in the
      myelomonocytic lineage. Low expression levels of RARgamma2 and RXRbeta remained
      unchanged, irrespective of differentiation pathway. Consistent with the gene
      expression patterns, RARalpha agonists and antagonists stimulated myelomonocytic
      and erythroid differentiation of FDCP-mixA4 cells, respectively. Taken together,
      these results suggest that erythropoiesis and granulopoiesis require diminished
      and enhanced RARalpha activities, respectively, which at physiological all-trans
      retinoic acid (RA) concentrations may be accomplished by reciprocal effects of
      EPO and myelomonocytic growth factors on its expression. This hypothesis is
      corroborated by data showing that RA, which positively regulates RARalpha2
      expression, can exert inhibitory effects on erythroid differentiation.

PMID- 11588054
TI  - An IRP-like protein from Plasmodium falciparum binds to a mammalian iron
      responsive element.
AB  - This study cloned and sequenced the complementary DNA (cDNA) encoding of a
      putative malarial iron responsive element-binding protein (PfIRPa) and confirmed
      its identity to the previously identified iron-regulatory protein (IRP)-like cDNA
      from Plasmodium falciparum. Sequence alignment showed that the plasmodial
      sequence has 47% identity with human IRP1. Hemoglobin-free lysates obtained from
      erythrocyte-stage P falciparum contain a protein that binds a consensus mammalian
      iron-responsive element (IRE), indicating that a protein(s) with iron-regulatory
      activity was present in the lysates. IRE-binding activity was found to be iron
      regulated in the electrophoretic mobility shift assays. Western blot analysis
      showed a 2-fold increase in the level of PfIRPa in the desferrioxamine-treated
      cultures versus control or iron-supplemented cells. Malarial IRP was detected by
      anti-PfIRPa antibody in the IRE-protein complex from P falciparum lysates.
      Immunofluorescence studies confirmed the presence of PfIRPa in the infected red
      blood cells. These findings demonstrate that erythrocyte P falciparum contains an
      iron-regulated IRP that binds a mammalian consensus IRE sequence, raising the
      possibility that the malaria parasite expresses transcripts that contain IREs and
      are iron-dependently regulated.

PMID- 11588056
TI  - Molecular regulation of CC-chemokine receptor 3 expression in human T helper 2
      cells.
AB  - In developing T helper 1 (Th1) and Th2 cells the acquisition of effector function
      is intimately connected with the acquisition of new migratory capacities, as
      exemplified by differential expression of chemokine receptors. This study
      investigates the molecular mechanisms responsible for Th2-restricted expression
      of the CC-chemokine receptor 3 (CCR3). The minimal promoter in T cells was
      identified in the -149 base pair (bp) upstream sequence that contains a positive
      regulatory element. A strong negative element was also localized in the flanking
      intronic sequence. The study further investigates the role of chromatin
      remodeling in the regulation of this Th2-specific gene. Drugs that affect the
      chromatin structure facilitate CCR3 expression in T cells. Furthermore, in
      differentiating Th2 cells, selected regions are associated with acetylated-H3
      histones and become more accessible to DNase I. These results suggest that in Th2
      cells both cytokine production and migratory capacity are regulated through a
      similar mechanism involving chromatin remodeling.

PMID- 11588057
TI  - TT virus contaminates first-generation recombinant factor VIII concentrates.
AB  - Recombinant factor VIII and factor IX concentrates, human-plasma-derived albumin,
      and samples from previously untreated patients with hemophilia were examined for
      the presence of TT virus (TTV) by using polymerase chain reaction testing. Blood
      samples from the patients were obtained prospectively before and every 3 to 6
      months after therapy was begun. TTV was detected in 23.5% of the recombinant
      product lots and 55.5% of the albumin lots tested. Only first-generation factor
      VIII recombinant concentrates stabilized with human albumin were positive for
      TTV, whereas all second-generation (human protein-free) concentrates were
      negative for the virus. In 59% of patients treated with either first- or second
      generation recombinant factor concentrates, TTV infection developed at some point
      after the initial infusion. Infection with TTV in these patients before and after
      treatment did not appear to be clinically important. Thus, first-generation
      recombinant factor VIII concentrates may contain TTV and the source of the viral
      contamination may be human albumin.

PMID- 11588058
TI  - Loss of blood CD11c(+) myeloid and CD11c(-) plasmacytoid dendritic cells in
      patients with HIV-1 infection correlates with HIV-1 RNA virus load.
AB  - Human blood contains at least 2 subpopulations of antigen-presenting dendritic
      cells (DCs) that can be differentiated by their expression of CD11c. Myeloid DCs
      (myDCs), which are CD11c(+), trap invading pathogens in the tissues and then
      migrate to lymphoid tissues where they stimulate pathogen-specific T-cell
      responses. Plasmacytoid DCs (pcDCs), which are CD11c(-), secrete interferon-alpha
      in response to viral infections. This study reports that in HIV-1 infection there
      is a progressive depletion of both these DC populations and that this correlates
      with an increasing HIV-1 plasma virus load. The median numbers of myDCs and pcDCs
      were 6978/mL and 9299/mL, respectively, in healthy male controls and 2298/mL and
      1640/mL, respectively, in patients with more than 10(5) HIV-1 RNA copies/mL. Both
      DC populations expressed CD4, CCR5, and CXCR4. The findings suggest that loss of
      DCs in HIV infection may contribute to disease progression.

PMID- 11588059
TI  - Effect of a large deletion of the basic domain of mi transcription factor on
      differentiation of mast cells.
AB  - The mi transcription factor (MITF) is a basic-helix-loop-helix-leucine zipper
      transcription factor that is important for the development of mast cells.
      Cultured mast cells (CMCs) of mi/mi genotype express abnormal MITF (mi-MITF), but
      CMCs of tg/tg genotype do not express any MITFs. It was previously reported that
      mi/mi CMCs showed more severe abnormalities than tg/tg CMCs, indicating that mi
      MITF had inhibitory function. Whereas mi-MITF contains a single amino acid
      deletion in the basic domain, MITF encoded by mi(ew) allele (ew-MITF) deletes 16
      of 21 amino acids of the basic domain. Here the effect of a large deletion of the
      basic domain was examined. In mi(ew)/mi(ew) CMCs, the expression pattern of genes
      whose transcription was affected by MITF was comparable to that of tg/tg CMCs
      rather than to that of mi/mi CMCs. This suggested that ew-MITF lacked any
      functions. The part of the basic domain deleted in ew-MITF appeared necessary for
      either transactivation or inhibition of transactivation.

PMID- 11588060
TI  - Detection of tryptase in cytoplasmic granules of basophils in patients with
      chronic myeloid leukemia and other myeloid neoplasms.
AB  - Tryptases are serine proteases primarily expressed in mast cells. Normal blood
      basophils express only trace amounts of the enzyme. However, recent
      immunohistochemical studies have raised the possibility that neoplastic basophils
      express significant amounts of tryptase. In this study, tryptase expression was
      analyzed in normal and neoplastic basophils by immunoelectron microscopy using
      antitryptase monoclonal antibody G3. Basophils were obtained from patients with
      chronic myeloid leukemia (CML), idiopathic myelofibrosis (IMF), and
      myelodysplastic syndrome (MDS), and from healthy donors. Tryptase-immunoreactive
      material was detected in cytoplasmic granules of basophils in CML, IMF, and MDS.
      By contrast, normal basophils did not contain significant amounts of tryptase by
      immunoelectron microscopy. As assessed by reverse transcription-polymerase chain
      reaction, neoplastic basophils contained messenger RNA (mRNA) for alpha-tryptase,
      but no beta-tryptase mRNA. In summary, these data provide evidence that
      neoplastic basophils in CML, IMF, and MDS can express detectable amounts of
      tryptase. Therefore, tryptase should not be regarded as specific for mast cells
      when neoplastic myeloid cells are analyzed.

PMID- 11588061
TI  - Genetic polymorphism in exon 4 of cytochrome P450 CYP2C9 may be associated with
      warfarin sensitivity in Chinese patients.
AB  - CYP2C9 polymorphisms reported in Caucasians (Arg144Cys in exon 3 and Ile359Leu in
      exon 7) are extremely uncommon in Chinese persons. The genotype of CYP2C9 in this
      population was characterized to investigate its relation with the interindividual
      variation in warfarin dosages. Eighty-nine Chinese patients receiving warfarin
      were recruited. Target sequences in CYP2C9 in exons 1, 4, and 5 were amplified by
      polymerase chain reaction, followed by direct sequencing. Polymorphisms at 4
      positions were demonstrated in exon 4. Heterozygosities for 608TTG>GTG
      (Leu208Val), 561CAG>CCG (Gln192Pro), 537CAT>CCT (His184Pro), and 527ATT>CTT
      (Ile181Leu) existed at frequencies 0.75, 0.20, 0.10, and 0.09, respectively.
      Seventeen patients (frequency, 0.19) were homozygous for Val208. The common
      genotypic combinations at these loci are Ile181/His184/Gln192/Leu208Val (n = 50),
      Ile181/His184/Gln192/Val208 (n = 15), Ile181/His184/Gln192/Leu208 (n = 4),
      Ile181/His184/Gln192Pro/Leu208Val (n = 6), Ile181/His184Pro/Gln192Pro/Leu208Val
      (n = 4), and Ile181Leu/His184/Gln192Pro/ Leu208Val (n = 4). At codon 208,
      heterozygous Leu208Val and homozygous Val208 appeared to have a lower warfarin
      dose requirement than the homozygous Leu208. Patients who are heterozygous for
      Ile181Leu had a higher warfarin dose requirement than the homozygous Ile181.
      Amplified sequences in exons 1 and 5 did not exhibit polymorphism. In conclusion,
      Chinese patients showed genetic polymorphisms of CYP2C9 in exon 4 and at codon
      208; most were heterozygous Leu208Val and homozygous Val208. Homozygous Leu208, a
      common allele in Caucasians, is uncommon in this cohort. The significance of
      these CYP2C9 polymorphic alleles remains to be determined.

PMID- 11588062
TI  - Postoperative starvation after gastrointestinal surgery. Early feeding is
      beneficial.

PMID- 11588063
TI  - Equity versus efficiency: a dilemma for the NHS. If the NHS is serious about
      equity it must offer guidance when principles conflict.

PMID- 11588065
TI  - Qualitative research in systematic reviews. Has established a place for itself.

PMID- 11588064
TI  - Screening for prostate cancer in the UK. Seems to be creeping in by the back
      door.

PMID- 11588066
TI  - Forthcoming theme issues and how we chose them. The web allows readers to
      participate in the decision.

PMID- 11588074
TI  - Doctors must speak out over war and humanitarian crises.

PMID- 11588068
TI  - FDA warns Merck over its promotion of rofecoxib.

PMID- 11588075
TI  - European women's group calls for human papillomavirus testing.

PMID- 11588076
TI  - Health maintenance organisations drop Medicare beneficiaries.

PMID- 11588077
TI  - Early enteral feeding versus "nil by mouth" after gastrointestinal surgery:
      systematic review and meta-analysis of controlled trials.
AB  - OBJECTIVE: To determine whether a period of starvation (nil by mouth) after
      gastrointestinal surgery is beneficial in terms of specific outcomes. DESIGN:
      Systematic review and meta-analysis of randomised controlled trials comparing any
      type of enteral feeding started within 24 hours after surgery with nil by mouth
      management in elective gastrointestinal surgery. Three electronic databases
      (PubMed, Embase, and the Cochrane controlled trials register) were searched,
      reference lists checked, and letters requesting details of unpublished trials and
      data sent to pharmaceutical companies and authors of previous trials. MAIN
      OUTCOME MEASURES: Anastomotic dehiscence, infection of any type, wound infection,
      pneumonia, intra-abdominal abscess, length of hospital stay, and mortality.
      RESULTS: Eleven studies with 837 patients met the inclusion criteria. In six
      studies patients in the intervention group were fed directly into the small bowel
      and in five studies patients were fed orally. Early feeding reduced the risk of
      any type of infection (relative risk 0.72, 95% confidence interval 0.54 to 0.98,
      P=0.036) and the mean length of stay in hospital (number of days reduced by 0.84,
      0.36 to 1.33, P=0.001). Risk reductions were also seen for anastomotic dehiscence
      (0.53, 0.26 to 1.08, P=0.080), wound infection, pneumonia, intra-abdominal
      abscess, and mortality, but these failed to reach significance (P>0.10). The risk
      of vomiting was increased among patients fed early (1.27, 1.01 to 1.61, P=0.046).
      CONCLUSIONS: There seems to be no clear advantage to keeping patients nil by
      mouth after elective gastrointestinal resection. Early feeding may be of benefit.
      An adequately powered trial is required to confirm or refute the benefits seen in
      small trials.

PMID- 11588078
TI  - Efficacy of progesterone and progestogens in management of premenstrual syndrome:
      systematic review.
AB  - OBJECTIVE: To evaluate the efficacy of progesterone and progestogens in the
      management of premenstrual syndrome. DESIGN: Systematic review of published
      randomised, placebo controlled trials. STUDIES REVIEWED: 10 trials of
      progesterone therapy (531 women) and four trials of progestogen therapy (378
      women). MAIN OUTCOME MEASURES: Proportion of women whose symptoms showed
      improvement with progesterone preparations (suppositories and oral micronised).
      Proportion of women whose symptoms showed improvement with progestogens.
      Secondary analysis of efficacy of progesterone and progestogens in managing
      physical and behavioural symptoms. RESULTS: Overall standardised mean difference
      for all trials that assessed efficacy of progesterone (by both routes of
      administration) was -0.028 (95% confidence interval -0.017 to -0.040). The odds
      ratio was 1.05 (1.03 to 1.08) in favour of progesterone, indicating no clinically
      important difference between progesterone and placebo. For progestogens the
      overall standardised mean was -0.036 (-0.014 to -0.060), which corresponds to an
      odds ratio of 1.07 (1.03 to 1.11) showing a statistically, but not clinically,
      significant improvement for women taking progestogens. CONCLUSION: The evidence
      from these meta-analyses does not support the use of progesterone or progestogens
      in the management of premenstrual syndrome.

PMID- 11588079
TI  - Communication difficulties during 999 ambulance calls: observational study.

PMID- 11588080
TI  - Bad press for doctors: 21 year survey of three national newspapers.

PMID- 11588081
TI  - Drug points. Exacerbation of angina associated with latanoprost.

PMID- 11588082
TI  - Identifying predictors of high quality care in English general practice:
      observational study.
AB  - OBJECTIVES: To assess variation in the quality of care in general practice and
      identify factors associated with high quality care. DESIGN: Observational study.
      SETTING: Stratified random sample of 60 general practices in six areas of
      England. OUTCOME MEASURES: Quality of management of chronic disease (angina,
      asthma in adults, and type 2 diabetes) and preventive care (rates of uptake for
      immunisation and cervical smear), access to care, continuity of care, and
      interpersonal care (general practice assessment survey). Multiple logistic
      regression with multilevel modelling was used to relate each of the outcome
      variables to practice size, routine booking interval for consultations,
      socioeconomic deprivation, and team climate. RESULTS: Quality of clinical care
      varied substantially, and access to care, continuity of care, and interpersonal
      care varied moderately. Scores for asthma, diabetes, and angina were 67%, 21%,
      and 17% higher in practices with 10 minute booking intervals for consultations
      compared with practices with five minute booking intervals. Diabetes care was
      better in larger practices and in practices where staff reported better team
      climate. Access to care was better in small practices. Preventive care was worse
      in practices located in socioeconomically deprived areas. Scores for
      satisfaction, continuity of care, and access to care were higher in practices
      where staff reported better team climate. CONCLUSIONS: Longer consultation times
      are essential for providing high quality clinical care. Good teamworking is a key
      part of providing high quality care across a range of areas and may need specific
      support if quality of care is to be improved. Additional support is needed to
      provide preventive care to deprived populations. No single type of practice has a
      monopoly on high quality care: different types of practice may have different
      strengths.

PMID- 11588084
TI  - Effective physiotherapy.

PMID- 11588085
TI  - ABC of the upper gastrointestinal tract. Oesophagus: Atypical chest pain and
      motility disorders.

PMID- 11588087
TI  - Bone densitometry is not a good predictor of hip fracture.

PMID- 11588088
TI  - Coping with complexity: educating for capability.

PMID- 11588090
TI  - Terminology used in article on cloning was incorrect.

PMID- 11588091
TI  - Preventing suicides must remain a priority.

PMID- 11588092
TI  - Symphysiotomies are important option in developing world.

PMID- 11588093
TI  - Prices of CD4 assays and viral load tests must be reduced for developing
      countries.

PMID- 11588094
TI  - Free supply of knowledge is good for developing countries.

PMID- 11588095
TI  - Tobacco control policy is regarded as fascism in Japan.

PMID- 11588096
TI  - Revalidation and assessment: giving marks might help.

PMID- 11588099
TI  - Pharmacological modulation of monovalent cation currents through the epithelial
      Ca2+ channel ECaC1.
AB  - 1. The recent identification of the epithelial Ca(2+) channel, ECaC1, represents
      a major step forward in our knowledge of renal Ca(2+) handling. ECaC1 constitutes
      the rate-limiting apical Ca(2+) entry mechanism of active, transcellular Ca(2+)
      reabsorption. This unique highly selective Ca(2+) channel shares a low but
      significant homology with transient receptor potential (TRP) channels and
      vanilloid receptors (VR). 2. We have studied the pharmacological modulation of
      currents through ECaC1 heterologously expressed in HEK 293 cells. Monovalent
      cation currents were measured by use of the whole cell patch clamp technique in
      cells dialysed with 10 mM BAPTA or 10 mM EGTA to prevent the fast Ca(2+)
      dependent inactivation of ECaC1. 3. Several modulators were tested, including
      inorganic cations, putative store-operated Ca(2+) entry (SOC) blockers, the
      vanilloid receptor (VR-1) blocker capsazepine, protein tyrosine kinase blockers,
      calmodulin antagonists and ruthenium red. 4. Ruthenium red and econazole appeared
      to be the most effective inhibitors of currents through ECaC1, with IC(50) values
      of 111 nM and 1.3 microM, respectively, whereas the selective SOC inhibitor,
      SKF96365, was nearly ineffective. 5. The divalent cation current block profile
      for ECaC1 is Pb(2+)=Cu(2+) >Zn(2+) >Co(2+) >Fe(2+) with IC(50) values between 1
      and approximately 10 microM. 6. In conclusion, ECaC activity is effectively
      inhibited by various compounds including ruthenium red, antimycotic drugs and
      divalent cations, which might be useful tools for pharmacological manipulation
      and several disorders related to Ca(2+) homeostasis could benefit from such
      developments.

PMID- 11588100
TI  - Vascular smooth muscle relaxation mediated by nitric oxide donors: a comparison
      with acetylcholine, nitric oxide and nitroxyl ion.
AB  - 1. Vasorelaxant properties of three nitric oxide (NO) donor drugs (glyceryl
      trinitrate, sodium nitroprusside and spermine NONOate) in mouse aorta
      (phenylephrine pre-contracted) were compared with those of endothelium-derived NO
      (generated with acetylcholine), NO free radical (NO*; NO gas solution) and
      nitroxyl ion (NO(-); from Angeli's salt). 2. The soluble guanylate cyclase
      inhibitor, ODQ (1H-(1,2,4-)oxadiazolo(4,3-a)-quinoxalin-1-one; 0.3, 1 and 10
      microM), concentration-dependently inhibited responses to all agents. 10 microM
      ODQ abolished responses to acetylcholine and glyceryl trinitrate, almost
      abolished responses to sodium nitroprusside but produced parallel shifts (to a
      higher concentration range; no depression in maxima) in the concentration
      response curves for NO gas solution, Angeli's salt and spermine NONOate. 3. The
      NO* scavengers, carboxy-PTIO, (2-(4-carboxyphenyl)-4,4,5,5-tetramethyl
      imidazoline-1-oxyl-3-oxide; 100 microM) and hydroxocobalamin (100 microM), both
      inhibited responses to NO gas solution and to the three NO donor drugs, but not
      Angeli's salt. Hydroxocobalamin, but not carboxy-PTIO, also inhibited responses
      to acetylcholine. 4. The NO(-) inhibitor, L-cysteine (3 mM), inhibited responses
      to Angeli's salt, acetylcholine and the three NO donor drugs, but not NO gas
      solution. 5. The data suggest that, in mouse aorta, responses to all three NO
      donors involve (i) activation of soluble guanylate cyclase, but to differing
      degrees and (ii) generation of both NO* and NO(-). Glyceryl trinitrate and sodium
      nitroprusside, which generate NO following tissue bioactivation, have profiles
      resembling the profile of endothelium-derived NO more than that of exogenous NO.
      Spermine NONOate, which generates NO spontaneously outside the tissue, was the
      drug that most closely resembled (but was not identical to) exogenous NO.

PMID- 11588101
TI  - Effects of local cytochalasin D delivery on smooth muscle cell migration and on
      collar-induced intimal hyperplasia in the rabbit carotid artery.
AB  - 1. Smooth muscle cell (SMC) migration has been implicated in neointima formation
      after angioplasty. Therefore, we investigated whether cytochalasin D, a fungal
      metabolite that inhibits actin filament formation, suppressed SMC migration and
      collar-induced intimal hyperplasia in the rabbit carotid artery. 2. To establish
      effective concentrations, contractions of carotid artery rings to phenylephrine
      were determined after incubation with cytochalasin D (10(-8) - 10(-6) M) for 30
      min or 3 days. In vitro cell migration was studied using carotid artery explants
      and a modified Boyden chamber with SMCs isolated from the rabbit aorta. The in
      vivo effect was tested after infusion of 10(-8) - 10(-4) M cytochalasin D into
      collars placed around the left carotid artery; collars placed around the right
      artery served as controls. 3. Contractions to phenylephrine decreased after 30
      min or 3 days exposure to 10(-7) and 10(-6) M cytochalasin D; the effect was
      partly reversible. These concentrations also inhibited cellular outgrowth and SMC
      migration in the in vitro assays. 4. Immunohistochemistry showed that local
      delivery of 10(-5) or 10(-4) M cytochalasin D for 2 weeks suppressed collar
      induced alpha-SMC actin expression in the intima by 68% and 84% respectively.
      However, the cross-sectional area of the intima was not reduced due to an influx
      of T-lymphocytes and macrophages. 5. It is concluded that cytochalasin D
      suppressed SMC contractility and migration in vitro. Although perivascular
      infusion of cytochalasin D inhibited collar-induced SMC migration from media to
      intima in vivo as well, the intimal hyperplasia was not reduced due to
      concomitant development of an inflammatory response.

PMID- 11588102
TI  - Common mechanisms of inhibition for the Na+/glucose (hSGLT1) and Na+/Cl-/GABA
      (hGAT1) cotransporters.
AB  - 1. Electrophysiological methods were used to investigate the interaction of
      inhibitors with the human Na(+)/glucose (hSGLT1) and Na(+)/Cl(-)/GABA (hGAT1)
      cotransporters. Inhibitor constants were estimated from both inhibition of
      substrate-dependent current and inhibitor-induced changes in cotransporter
      conformation. 2. The competitive, non-transported inhibitors are substrate
      derivatives with inhibition constants from 200 nM (phlorizin) to 17 mM (esculin)
      for hSGLT1, and 300 nM (SKF89976A) to 10 mM (baclofen) for hGAT1. At least for
      hSGLT1, values determined using either method were proportional over 5-orders of
      magnitude. 3. Correlation of inhibition to structure of the inhibitors resulted
      in a pharmacophore for glycoside binding to hSGLT1: the aglycone is coplanar with
      the pyranose ring, and binds to a hydrophobic/aromatic surface of at least 7x12A.
      Important hydrogen bond interactions occur at five positions bordering this
      surface. 4. In both hSGLT1 and hGAT1 the data suggests that there is a large,
      hydrophobic inhibitor binding site approximately 8A from the substrate binding
      site. This suggests an architectural similarity between hSGLT1 and hGAT1. There
      is also structural similarity between non-competitive and competitive inhibitors,
      e.g., phloretin is the aglycone of phlorizin (hSGLT1) and nortriptyline resembles
      SKF89976A without nipecotic acid (hGAT1). 5. Our studies establish that
      measurement of the effect of inhibitors on presteady state currents is a valid
      non-radioactive method for the determination of inhibitor binding constants.
      Furthermore, analysis of the presteady state currents provide novel insights into
      partial reactions of the transport cycle and mode of action of the inhibitors.

PMID- 11588103
TI  - The role of the hydrophilic Asn230 residue of the mu-opioid receptor in the
      potency of various opioid agonists.
AB  - 1. To investigate the effect of the hydrophilic Asn amino acid at position 230 of
      the human mu-opioid receptor (hMOR230) on the potency of various agonists, we
      mutated this residue to Thr and Leu (hMORN230T and hMORN230L respectively). 2.
      Taking advantage of the functional coupling of the opioid receptor with the
      heteromultimeric G-protein-coupled inwardly rectifying K(+) (GIRK1/GIRK2)
      channel, either the wild type hMOR or one of the mutated receptors (hMORN230L or
      hMORN230T) were functionally coexpressed with GIRK1/GIRK2 channels and a
      regulator of G-protein signalling (RGS4) in Xenopus laevis oocytes. 3. The two
      microelectrode voltage clamp technique was used to measure the opioid receptor
      activated GIRK1/GIRK2 channel responses. The potency of [D-Ala(2),N
      MePhe(4),Gly(5)-ol]-enkephalin (DAMGO), remained unaffected as measured via
      hMORN230T and hMORN230L, while the potency of fentanyl and morphine significantly
      increased via these mutated receptors. 4. Our results are indicative for the
      existence of hydrophobic interactions between a methyl-group of the side chain of
      Thr or Leu on the one hand and the piperidine-ring of fentanyl and the hexene
      ring of morphine on the other. The mutations also had no influence on the potency
      of morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G). 5. We conclude
      that the hydrophilic side chain of Asn in position 230 is not involved in the
      formation of a H-bond with the aliphatic alcohol of morphine and that an
      enhancement of the potency of morphine and fentanyl can be explained by mutating
      this residue towards more hydrophobic amino acids.

PMID- 11588104
TI  - Determination of effects of antiepileptic drugs on SNAREs-mediated hippocampal
      monoamine release using in vivo microdialysis.
AB  - 1. To elucidate possible mechanisms underlying the effects of carbamazepine
      (CBZ), valproate (VPA) and zonisamide (ZNS) on neurotransmitter exocytosis, the
      interaction between these three antiepileptic drugs (AEDs) and botulinum toxins
      (BoNTs) on basal, Ca(2+)- and K(+)-evoked release of dopamine (DA) and serotonin
      (5-HT) were determined by microdialysis in the hippocampus of freely moving rats.
      2. Basal release of monoamine was decreased by pre-microinjection of the syntaxin
      inhibitor, BoNT/C, but only weakly affected by the synaptobrevin inhibitor,
      BoNT/B. Ca(2+)-evoked release was inhibited by BoNT/C selectively. K(+)-evoked
      release was reduced by BoNT/B predominantly and BoNT/C weakly. 3. Perfusion with
      low and high concentrations of CBZ and ZNS increased and decreased basal
      monoamine release, respectively. Perfusion with VPA increased basal 5-HT release
      concentration-dependently, whereas basal DA release was affected by VPA biphasic
      concentration-dependently, similar to CBZ and ZNS. This stimulatory action of
      AEDs on basal release was inhibited by BoNT/C predominantly. 4. Ca(2+)-evoked
      monoamine release was increased by low concentrations of CBZ, ZNS and VPA, but
      decreased by high concentrations. These effects of the AEDs on Ca(2+)-evoked
      release were inhibited by BoNT/C, but not by BoNT/B. 5. K(+)-evoked monoamine
      release was reduced by AEDs concentration-dependently. The inhibitory effect of
      these three AEDs on K(+)-evoked release was inhibited by BoNT/B, but not by
      BoNT/C. 6. These findings suggest that the therapeutic-relevant concentration of
      CBZ, VPA and ZNS affects exocytosis of DA and 5-HT, the enhancement of syntaxin
      mediated monoamine release during resting stage, and the inhibition of
      synaptobrevin-mediated release during depolarizing stage.

PMID- 11588105
TI  - Effects of agents that inactivate free radical NO (NO*) on nitroxyl anion
      mediated relaxations, and on the detection of NO* released from the nitroxyl
      anion donor Angeli's salt.
AB  - 1. The effects of agents that inactivate free radical nitric oxide (carboxy-PTIO,
      hydroxocobalamin and pyrogallol) were tested on relaxations produced by the
      nitroxyl anion (NO(-)) donor Angeli's salt in rat aortic rings and anococcygeus
      muscles. The amount of NO(*) generated from Angeli's salt in the presence of
      these agents was measured using a NO(*)-selective electrode sensor. 2. Carboxy
      PTIO (100, 300 microM), hydroxocobalamin (30, 100 microM) and pyrogallol (10, 30
      microM) significantly reduced relaxations produced by Angeli's salt (0.3 microM)
      in aortic rings but not in anococcygeus muscles. 3. NO(*) generated from Angeli's
      salt (0.1 - 10 microM), as detected by the sensor electrode, was less than 0.5%
      of the amount of Angeli's salt added. Carboxy-PTIO (100 microM) and
      hydroxocobalamin (30 microM), but not pyrogallol significantly increased the
      amount of NO(*) detected. 4. In the presence of an oxidizing agent copper [II]
      (as CuSO(4) 100 microM), the amount of NO(*) detected from 0.3 microM of Angeli's
      salt increased from an undetectable level of 142.7+/-15.7 nM (equivalent to 47.6%
      of Angeli's salt added). Under these conditions, carboxy-PTIO, hydroxocobalamin
      and pyrogallol significantly reduced the amount of NO(*) detected from Angeli's
      salt as well as the signal generated by an equivalent amount of authentic NO
      (0.33 microM). 5. The difference in effects of these agents on relaxations to
      Angeli's salt in the aorta and the anococcygeus muscle may be explained by the
      ready conversion of NO(-) to NO(*) in the aorta through an unidentified
      mechanism, which makes NO(-) susceptible to inactivation by these agents.
      Furthermore, in addition to inactivating NO(*), carboxy-PTIO and hydroxocobalamin
      may themselves oxidize NO(-) to NO(*), albeit slightly.

PMID- 11588106
TI  - Orphanin FQ/nociceptin attenuates the development of morphine tolerance in rats.
AB  - 1. Recent evidence from studies in mice lacking the opioid receptor-like (ORL-1)
      receptor and from experiments using antibodies raised against orphanin
      FQ/nociceptin (OFQ/N) suggest that this peptide may be involved in morphine
      tolerance. In the present study we sought to investigate if administration of
      exogenous OFQ/N would modulate the development of tolerance to the
      antinociceptive effect of morphine. 2. Rats were treated for 3 days with either
      saline or morphine (10 mg kg(-1), s.c.) followed, 15 and 75 min later, by two
      intracerebroventricular injections of either artificial cerebrospinal fluid
      (aCSF) or OFQ/N. The dose of OFQ/N was doubled each day (7.5, 15, 30 nmol). On
      day 4, rats were tested on a hot plate apparatus before and 30, 60 and 90 min
      after morphine administration. 3. Repeated OFQ/N treatment did not affect basal
      nociceptive responses or morphine-induced antinociception. However, the same
      treatment significantly attenuated the development of morphine tolerance. 4.
      Since learning and memory could contribute to the development of morphine
      tolerance, in subsequent studies, we examined the effect of OFQ/N administered in
      the CA3 region of the hippocampus, where OFQ/N has been shown to block LTP and
      impair spatial memory. A greater attenuation of morphine tolerance with no
      alteration of baseline hot plate latency or morphine-induced antinociception was
      observed when OFQ/N was administered in this area of the rat brain. 5. Taken
      together, our results demonstrate that OFQ/N may act in the hippocampus to
      attenuate morphine tolerance.

PMID- 11588107
TI  - The KATP channel opener diazoxide protects cardiac myocytes during metabolic
      inhibition without causing mitochondrial depolarization or flavoprotein
      oxidation.
AB  - 1. The K(ATP) channel opener diazoxide has been proposed to protect cardiac
      muscle against ischaemia by opening mitochondrial K(ATP) channels to depolarize
      the mitochondrial membrane potential, DeltaPsi(m). We have used the fluorescent
      dye TMRE to measure DeltaPsi(m) in adult rat freshly isolated cardiac myocytes
      exposed to diazoxide and metabolic inhibition. 2. Diazoxide, at concentrations
      that are highly cardioprotective (100 or 200 microM), caused no detectable
      increase in TMRE fluorescence (n=27 cells). However, subsequent application of
      the protonophore FCCP, which should collapse DeltaPsi(m), led to large increases
      in TMRE fluorescence (>300%). 3. Metabolic inhibition (MI: 2 mM NaCN+1 mM
      iodoacetic acid (IAA) led to an immediate partial depolarization of DeltaPsi(m),
      followed after a few minutes delay by complete depolarization which was
      correlated with rigor contracture. Removal of metabolic inhibition led to abrupt
      mitochondrial repolarization followed in many cells by hypercontracture,
      indicated by cell rounding and loss of striated appearance. 4. Prior application
      of diazoxide (100 microM) reduced the number of cells that hypercontracted after
      metabolic inhibition from 63.7+/-4.7% to 24.2+/-1.8% (P< 0.0001). 5
      hydroxydeanoate (100 microM) reduced the protection of diazoxide (46.8+/-2.7%
      cells hypercontracted, P< 0.0001 vs diazoxide alone). 5. Diazoxide caused no
      detectable change in flavoprotein autofluorescence (n=26 cells). 6. Our results
      suggest that mitochondrial depolarization and flavoprotein oxidation are not
      inevitable consequences of diazoxide application in intact cardiac myocytes, and
      that they are also not essential components of the mechanism by which it causes
      protection.

PMID- 11588108
TI  - Induction of cyclooxygenase-2 protein by lipoteichoic acid from Staphylococcus
      aureus in human pulmonary epithelial cells: involvement of a nuclear factor-kappa
      B-dependent pathway.
AB  - 1. This study investigated the role of protein kinase C (PKC) and transcription
      factor nuclear factor-kappaB (NF-kappaB) in cyclooxygenase-2 (COX-2) expression
      caused by lipoteichoic acid (LTA), a cell wall component of the gram-positive
      bacterium Staphylococcus aureus, in human pulmonary epithelial cell line (A549).
      2. LTA caused dose- and time-dependent increases in COX-2 expression and COX
      activity, and a dose-dependent increase in PGE(2) release in A549 cells. The LTA
      induced increases in COX-2 expression and COX activity were markedly inhibited by
      dexamethasone, actinomycin D or cyclohexamide, but not by polymyxin B, which
      binds and inactivates endotoxin. 3. The phosphatidylcholine-phospholipase C (PC
      PLC) inhibitor (D-609) and the phosphatidate phosphohydrolase inhibitor
      (propranolol) reduced the LTA-induced increases in COX-2 expression and COX
      activity, while phosphatidylinositol-phospholipase C inhibitor (U-73122) had no
      effect. The PKC inhibitors (Go 6976, Ro 31-8220 and GF 109203X) and NF-kappaB
      inhibitor, pyrrolidine dithiocarbamate (PDTC), also attenuated the LTA-induced
      increases in COX-2 expression and COX activity. 4. Treatment of A549 cells with
      LTA caused an increase in PKC activity in the plasma membrane; this stimulatory
      effect was inhibited by D-609, propranolol, or Go 6976, but not by U-73122. 5.
      Exposure of A549 cells to LTA caused a translocation of p65 NF-kappaB from the
      cytosol to the nucleus and a degradation of IkappaB-alpha in the cytosol.
      Treatment of A549 cells with LTA caused NF-kappaB activation by detecting the
      formation of NF-kappaB-specific DNA-protein complex in the nucleus; this effect
      was inhibited by dexamethasone, D-609, propranolol, Go 6976, Ro 31-8220, or PDTC.
      6. These results suggest that LTA might activate PC-PLC and phosphatidylcholine
      phospholipase D to induce PKC activation, which in turn initiates NF-kappaB
      activation, and finally induces COX-2 expression and PGE(2) release in human
      pulmonary epithelial cell line.

PMID- 11588109
TI  - Beneficial effects of the Ca2+ sensitizer EMD 57033 in exercising pigs with
      infarction-induced chronic left ventricular dysfunction.
AB  - 1. It is unknown how cardiac stimulation by Ca(2+) sensitization modulates the
      cardiovascular response to exercise when left ventricular (LV) function is
      chronically depressed following a myocardial infarction. We therefore
      investigated the effects of EMD 57033 at rest and during exercise and compared
      these to those of the mixed Ca(2+)-sensitizer/phosphodiesterase-III inhibitor
      pimobendan. 2. Pigs were chronically instrumented for measurement of
      cardiovascular performance. At the time of instrumentation, infarction was
      produced by coronary artery ligation (MI, n=12). Studies in MI were performed in
      the awake state, 2 - 3 weeks after infarction. 3. MI were characterized by a
      lower resting cardiac output (18%), stroke volume (30%) and LVdP/dt(max) (18%),
      and a doubling of LV end-diastolic pressure, compared to normal pigs (N, n=13).
      4. In 11 resting MI, intravenous EMD 57033 (0.2 - 0.8 mg kg(-1) min(-1))
      increased LVdP/dt(max) (57+/-5%) and stroke volume (26+/-6%) with no effect on
      heart rate, LV filling pressure, and myocardial O(2)-consumption, similar to N.
      5. In MI, the effects of EMD 57033 (0.4 mg kg(-1) min(-1), IV) on stroke volume
      and LVdP/dt(max) were maintained during treadmill exercise up to 85% of maximal
      heart rate, while heart rate was lower compared to control exercise (all P<0.05).
      In contrast, the effects of EMD57033 gradually waned in N at increasing intensity
      of exercise. 6. Compared to N, the cardiostimulatory effects of pimobendan (20
      microg kg(-1) min(-1), IV) were blunted in MI both at rest and during exercise
      compared to N. 7. In conclusion, the positive inotropic actions of the Ca(2+)
      sensitizer EMD 57033 are unmitigated in resting and exercising MI compared to N,
      while those of the mixed Ca(2+)-sensitizer/phosphodiesterase-III inhibitor
      pimobendan are blunted.

PMID- 11588110
TI  - Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice
      in a model of intestinal inflammation.
AB  - 1. We have studied the effect of cannabinoid agonists (CP 55,940 and cannabinol)
      on intestinal motility in a model of intestinal inflammation (induced by oral
      croton oil in mice) and measured cannabinoid receptor expression,
      endocannabinoids (anandamide and 2-arachidonylglycerol) and anandamide
      amidohydrolase activity both in physiological and pathophysiological states. 2.
      CP 55,940 (0.03 - 10 nmol mouse(-1)) and cannabinol (10 - 3000 nmol mouse(-1))
      were more active in delaying intestinal motility in croton oil-treated mice than
      in control mice. These inhibitory effects were counteracted by the selective
      cannabinoid CB(1) receptor antagonist SR141716A (16 nmol mouse(-1)). SR141716A (1
      - 300 nmol mouse(-1)), administered alone, increased intestinal motility to the
      same extent in both control and croton oil-treated mice. 3. Croton oil-induced
      intestinal inflammation was associated with an increased expression of CB(1)
      receptor, an unprecedented example of up-regulation of cannabinoid receptors
      during inflammation. 4. High levels of anandamide and 2-arachidonylglycerol were
      detected in the small intestine, although no differences were observed between
      control and croton oil-treated mice; by contrast anandamide amidohydrolase
      activity increased 2 fold in the inflamed small intestine. 5. It is concluded
      that inflammation of the gut increases the potency of cannabinoid agonists
      possibly by 'up-regulating' CB(1) receptor expression; in addition,
      endocannabinoids, whose turnover is increased in inflamed gut, might tonically
      inhibit intestinal motility.

PMID- 11588111
TI  - Inhibition of interleukin-12 production by auranofin, an anti-rheumatic gold
      compound, deviates CD4(+) T cells from the Th1 to the Th2 pathway.
AB  - 1. Interleukin-12 (IL-12) may play a central role in the development and
      progression of rheumatoid arthritis by driving the immune response towards T
      helper 1 (Th1) type responses characterized by high IFN-gamma and low IL-4
      production. In this study we investigated the effect of auranofin (AF), an anti
      rheumatic gold compound, on IL-12 production in mouse macrophages and dendritic
      cells, and studied whether AF-mediated inhibition of IL-12 production could
      regulate a cytokine profile of antigen (Ag)-primed CD4(+) Th cells. 2. Treatment
      with AF significantly inhibited IL-12 production in lipopolysaccharide (LPS)
      stimulated macrophages and also in CD40L-stimulated dendritic cells. AF
      pretreated macrophages reduced their ability to induce IFN-gamma and increased
      the ability to induce IL-4 in Ag-primed CD4(+) T cells. AF did not influence the
      cell surface expression of the class II MHC molecule and the costimulatory
      molecules CD80 and CD86. 3. Addition of recombinant IL-12 to cultures of AF
      pretreated macrophages and CD4(+) T cells restored IFN-gamma production in Ag
      primed CD4(+) T cells. 4. The in vivo administration of AF resulted in the
      inhibition of IL-12 production by macrophages stimulated in vitro with LPS or
      heat-killed Listeria monocytogenes (HKL), leading to the inhibition of Th1
      cytokine profile (decreased IFN-gamma and increased IL-4 production) in Ag-primed
      CD4(+) T cells. 5. These findings may explain some known effects of AF including
      anti-rheumatic effects and the inhibition of encephalitogenicity, and point to a
      possible therapeutic use of AF in the Th1-mediated immune diseases such as
      autoimmune diseases.

PMID- 11588112
TI  - Reduction of oxidative stress and AT1 receptor expression by the selective
      oestrogen receptor modulator idoxifene.
AB  - 1. The beneficial vasoprotective effects of oestrogens are hampered by their side
      effects on secondary sexual organs. Selective oestrogen receptor modulators
      (SERM) such as idoxifene may exert beneficial vascular effects without
      influencing cancerogenesis in breast or uterus. 2. In order to investigate
      vascular effects of selective oestrogen receptor modulators, we examined the
      impact of idoxifene on production of reactive oxygen species as well as AT1
      receptor expression in vascular smooth muscle cells (VSMC). 3. Idoxifene caused a
      concentration- and time-dependent down-regulation of AT1 receptor mRNA
      expression, as assessed by Northern analysis. The maximal effect was reached with
      10 micromol l(-1) idoxifene after a 4 h incubation period (33+/-7% of control
      levels). Western blots showed a similar down-regulation of AT1 receptor protein
      to 36+/-11% of control levels. 4. Confocal laserscanning microscopy using the
      redox sensitive marker 2',7'-dichlorofluorescein (DCF) and measurement of NAD(P)H
      oxidase activity in cell homogenates revealed that idoxifene effectively blunted
      the angiotensin II-induced production of reactive oxygen species. 5. In order to
      investigate the signal transduction involved in SERM-induced modulation of AT1
      receptor expression, VSMC were preincubation with PD98059, genistein, wortmannin,
      or N(omega)-Nitro-L-arginine. The results suggested that idoxifene caused AT1
      receptor down-regulation through nitric oxide-dependent pathways. 6. In
      conclusion, idoxifene reduces angiotensin II-evoked oxidative stress in VSMC.
      This could in part be explained by idoxifene-induced down-regulation of AT1
      receptor expression. These results demonstrate that the selective oestrogen
      receptor modulator idoxifene may exert beneficial vascular effects which could be
      useful for therapeutic regimen in postmenopausal women at risk for cardiovascular
      diseases.

PMID- 11588113
TI  - Protective effects of 5-HT1A receptor agonists against emotional changes produced
      by stress stimuli are related to their neuroendocrine effects.
AB  - 1. The effects of the 11beta-hydroxylase inhibitor metyrapone on the protective
      effects of serotonin (5-hydroxytryptamine; 5-HT)(1A) receptor agonists against
      emotional changes produced by acute restraint stress were examined in mice. 2.
      Changes in the emotional state of mice were evaluated in terms of changes in
      exploratory activity, i.e. total locomotor activity, number and duration of
      rearing and head-dipping behaviours, and latency to the first head-dipping, using
      an automatic hole-board apparatus. 3. Treatment with the 5-HT(1A) receptor
      agonists flesinoxan (1 mg kg(-1), i.p.) and R(+)-2-di-n-propylamino-8-hydroxy
      1,2,3,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT; 1 mg kg(-1), i.p.) 24 h
      prior to exposure to stress significantly suppressed the decrease in various
      exploratory behaviours that was observed immediately after the exposure to acute
      restraint stress (60 min). The effects of flesinoxan (1 mg kg(-1), i.p.) and 8-OH
      DPAT (1 mg kg(-1), i.p.) were antagonized by co-injection with N-[2-[4-(2
      methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide
      trihydrochloride (WAY100635; 1 mg kg(-1), i.p.), a selective 5-HT(1A) receptor
      antagonist. 4. Flesinoxan (1 mg kg(-1), i.p.) and 8-OH-DPAT (1 mg kg(-1) i.p.)
      significantly increased the plasma corticosterone level, and these effects of 5
      HT(1A) receptor agonists were dose-dependently blocked by pretreatment with
      metyrapone (12.5 and 25 mg kg(-1), s.c.). 5. Metyrapone (25 mg kg(-1), s.c.)
      alone did not modify the stress-induced changes in exploratory behaviours.
      Pretreatment with metyrapone (12.5 and 25 mg kg(-1), s.c.) partly antagonized the
      protective effects of flesinoxan (1 mg kg(-1), i.p.) and 8-OH-DPAT (1 mg kg(-1),
      i.p.) with regard to only the number and duration of head-dipping behaviours. 6.
      These results suggest that activation of the adrenocortical system via 5-HT(1A)
      receptors may facilitate some adaptive mechanism(s) involved in the recognition
      of and/or ability to cope with stressful situations.

PMID- 11588114
TI  - Guanosine 3': 5'-cyclic monophosphate-dependent pathway alterations in
      ventricular cardiomyocytes of spontaneously hypertensive rats.
AB  - 1. We investigated the effect of the NO-donor S-nitroso-N-acetyl-DL-penicillamine
      (SNAP) on cardiomyocytes isolated from control normotensive Wistar Kyoto (WKY)
      and spontaneously hypertensive (SHR) rats. 2. Ventricular cardiomyocytes were
      isolated from SHR and WKY hearts and imaging analysis of fura-2-loaded cells was
      performed in order to evaluate calcium transient in electrical field paced (0.5
      Hz) cells. 3. In WKY cardiomyocytes, 1 - 200 microM SNAP dose-dependently
      increased cyclic GMP content. In basal conditions, cyclic GMP content of SHR
      cardiomyocytes was significantly higher than in WKY, but SNAP failed to further
      increase cyclic GMP over the basal level. 4. In control conditions, the Delta F/F
      and decay time of the calcium transient were similar in both strains. In WKY
      cardiomyocytes, SNAP (1 - 100 microM) reduced the decay time. In SHR
      cardiomyocytes, SNAP was ineffective. Dibutyryl cyclic GMP (10(-6) - 10(-8) M), a
      membrane permeable cyclic GMP analogue, behaved similarly to SNAP. 5. In WKY and
      SHR cardiomyocytes, 10(-8) M isoprenaline similarly increased Delta F/F and
      decreased the decay time. SNAP and dibutyryl cyclic GMP prevented the effect of
      isoprenaline in WKY, whereas both molecules were ineffective in SHR
      cardiomyocytes. In WKY, SNAP effects were blocked by pretreating cells with the
      cGK inhibitor KT-5823. 6. Western blotting analysis of cGK type I showed that the
      enzyme was expressed in WKY isolated cardiomyocytes, but absent in four out of
      five SHR preparations. 7. We concluded that the low expression of cGKI may
      determine the lack of NO/cyclic GMP-dependent regulation on calcium transient in
      SHR cardiomyocytes. This alteration may contribute to the development of heart
      hypertrophy in hypertensive status.

PMID- 11588115
TI  - The new compound, LASSBio 294, increases the contractility of intact and saponin
      skinned cardiac muscle from Wistar rats.
AB  - 1. A new compound designated as LASSBio 294 (L-294), 3,4-methylenedioxybenzoyl-2
      thienylhydrazone, was synthesized as an alternative therapeutic for cardiac
      dysfunction. 2. L-294 increased in a dose-dependent manner the spontaneous
      contractions of isolated hearts from Wistar rats with maximal effect (128.0+/
      0.7% of control) observed at 25 microM. 3. The positive inotropic effect of L-294
      was also observed in electrically stimulated cardiac tissues from Wistar rats.
      The maximal increment of twitches, at 200 microM, was 163.1+/-18.4% for atrial,
      153.5+/-28.5% for papillary and 201.5+/-18.5% for ventricular muscles. 4. In
      saponin skinned ventricular cells: (a) L-294 present in the period of
      sarcoplasmic reticulum (SR) loading with Ca(2+) shifted the dose and caffeine
      induced contracture curve; (b) L-294 (100 microM) increased 40% the Ca(2+) uptake
      into SR; (c) L-294 did not significantly alter the sensitivity of contractile
      proteins to Ca(2+) in SR-disrupted skinned ventricular cells. 5. Retrograde
      perfusion of the isolated heart from Wistar rats with L-294 (100 microM) did not
      cause any significant change in rhythm, heart rate (control, 220+/-14.7 b.p.m.;
      246+/-24.6 b.p.m. for L-294), PR interval (control, 66.0+/-2.4 ms; 64.0+/-2.3 ms
      for L-294) or QRS duration (control, 28.8+/-3.4 ms; 32.0+/-2.0 ms for L-294). 6.
      These results suggest a novel mechanism for a positive cardioinotropic effect
      through an interaction with the Ca(2+) uptake/release process of the SR. The
      effect of L-294 could be explained by a pronounced increased accumulation of
      Ca(2+) into the SR.

PMID- 11588116
TI  - Increased contractile response to 5-hydroxytryptamine1-receptor stimulation in
      pulmonary arteries from chronic hypoxic rats: role of pharmacological synergy.
AB  - 1. 5-Hydroxytryptamine (5-HT)(1)-receptor-induced contraction is enhanced, or
      uncovered, by elevated vascular tone in many arteries including pulmonary
      arteries. In hypoxia-induced pulmonary hypertension, the endogenous tone of
      pulmonary arteries is elevated and this may contribute to increased 5-HT(1)
      receptor-induced contraction. Here we investigate the influence of vascular tone
      induced by endothelin-1 (ET-1), neuropeptide Y (NPY), KCl, 4-aminopyridine
      (inactivator of K(v) channels, 4-AP) or the calcium ionophore A23187 on
      contractile responses to the 5-HT(1)-receptor agonist 5-carboxamidotryptamine (5
      CT) in small muscular pulmonary arteries from control rats and rats exposed to
      chronic hypoxia. The influence of the nitric oxide synthase inhibitor N(omega)
      nitro-L-arginine methyl ester (L-NAME, 100 microM) was also studied. These
      conditions were chosen to mimic those that influence pulmonary vascular tone in
      hypoxia-induced pulmonary hypertension. 2. In control rat small pulmonary
      arteries, only high concentrations of 5-CT (>1 microM) induced vasoconstriction.
      Tone induced by NPY, 4-AP and A23187 had no effect on responses to 5-CT whilst
      responses to 5-CT were increased by ET-1- and KCl-induced tone. In the presence
      of L-NAME these responses to 5-CT were enhanced further. 3. Responses to 5-CT
      were enhanced 3 - 4 fold in small pulmonary arteries from hypoxia-exposed,
      pulmonary hypertensive rats and neither L-NAME nor increasing tone with NPY, 4
      AP, A23187, ET-1 or KCl had any further effect on responses to 5-CT. 4. The
      results suggest that inhibition of nitric oxide synthase combined with KCl- or ET
      1-induced vascular tone potentiates responses to 5-HT(1)-receptor-induced
      contraction in pulmonary arteries in a synergistic fashion and this mimics the
      effects of chronic hypoxic exposure.

PMID- 11588117
TI  - Mechanisms of hydralazine induced vasodilation in rabbit aorta and pulmonary
      artery.
AB  - 1. The directly acting vasodilator hydralazine has been proposed to act at an
      intracellular site in vascular smooth muscle to inhibit Ca(2+) release. 2. This
      study investigated the mechanism of action of hydralazine on rabbit aorta and
      pulmonary artery by comparing its effects on the tension generated by intact and
      beta-escin permeabilized vessels and on the cytoplasmic Ca(2+) concentration,
      membrane potential and K(+) currents of isolated vascular smooth muscle cells. 3.
      Hydralazine relaxed pulmonary artery and aorta with similar potency. It was
      equally effective at inhibiting phasic and tonic contractions evoked by
      phenylephrine in intact vessels and contractions evoked by inositol 1,4,5
      trisphosphate (IP(3)) in permeabilized vessels. 4. Hydralazine inhibited the
      contraction of permeabilized vessels and the increase in smooth muscle cell
      Ca(2+) concentration evoked by caffeine with similar concentration dependence,
      but with lower potency than its effect on IP(3) contractions. 5. Hydralazine had
      no effect on the relationship between Ca(2+) concentration and force generation
      in permeabilized vessels, but it slowed the rate at which maximal force was
      developed before, but not after, destroying sarcoplasmic reticulum function with
      the calcium ionophore, ionomycin. 6. Hydralazine had no effect on membrane
      potential or the amplitudes of K(+) currents recorded from isolated smooth muscle
      cells over the concentration range causing relaxation of intact vessels. 7. The
      results suggest that the main action of hydralazine is to inhibit the IP(3)
      induced release of Ca(2+) from the sarcoplasmic reticulum in vascular smooth
      muscle cells.

PMID- 11588118
TI  - Nitric oxide regulates human eosinophil adhesion mechanisms in vitro by changing
      integrin expression and activity on the eosinophil cell surface.
AB  - 1. The nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl
      ester (L-NAME), inhibits both rat and human eosinophil chemotaxis in vitro. Here,
      the role of nitric oxide (NO) in human eosinophil cell surface integrin
      expression and function was investigated. 2. Human peripheral blood eosinophils
      were treated with L-NAME (0.01 - 1.0 mM) and their adhesion to human fibronectin
      and serum observed. Adhesion of cells to fibronectin and serum increased by
      24.0+/-4.6 and 43.8+/-4.7%, respectively, when eosinophils were treated with 1.0
      mM L-NAME. Increased adhesion by L-NAME could be abolished when cells were co
      incubated with VLA-4- and Mac-1-specific monoclonal antibodies (mAbs). 3. The NO
      donor, sodium nitroprusside (2.5 mM), significantly inhibited eosinophil adhesion
      to fibronectin and serum by 34.3+/-4.5 and 45.2+/-5.6%, respectively. This
      inhibition was accompanied by a 4 fold increase in the levels of intracellular
      cyclic GMP. 4. Flow cytometrical analysis demonstrated that L-NAME induced an
      increased expression of CD11b (Mac-1) on the eosinophil cell surface of 36.3+/
      7.4%. L-NAME had no effect upon CD49d (VLA-4) expression. 5. Treatment of human
      eosinophils, in vitro, with H-[1,2,4] oxadiazolo quinoxalin-1-one (ODQ) (0.1 mM),
      an inhibitor of soluble guanylate cyclase, also significantly increased
      eosinophil adhesion to fibronectin and serum by 73.5+/-17.9 and 91.7+/-12.9%,
      respectively. This increase in adhesion could also be inhibited by co-incubation
      with the Mac-1 and VLA-4-specific mAbs. 6. In conclusion, results indicate that
      NO, via a cyclic GMP-dependent mechanism, inhibits the adhesion of human
      eosinophils to the extracellular matrix (ECM). This inhibition is accompanied by
      a decrease in the expression and function of the eosinophil's adhesion molecules,
      in particular, the expression of the Mac-1 integrin and the function of the VLA-4
      integrin.

PMID- 11588119
TI  - Changes in extracellular pH and myocardial ischaemia alter the cardiac effects of
      diadenosine tetraphosphate and pentaphosphate.
AB  - 1. The structural conformation of diadenosine tetraphosphate (Ap(4)A) and
      pentaphosphate (Ap(5)A) has been reported to alter as pH is reduced. As such, it
      is possible that the cardiac effects of Ap(4)A and Ap(5)A vary during acidosis
      and myocardial ischaemia due to changes in ligand structure, receptor proteins or
      intracellular signalling. 2. We investigated whether the cardiac
      electrophysiological and coronary vasomotor effects of Ap(4)A and Ap(5)A are
      preserved under conditions of extracellular acidosis (pH 6.5) and alkalosis (pH
      8.5) and whether Ap(4)A has any electrophysiological or antiarrhythmic effects
      during ischaemia. 3. Transmembrane right ventricular action potentials,
      refractory periods and coronary perfusion pressure were recorded from isolated,
      Langendorff-perfused guinea-pig hearts under constant flow conditions. The
      effects of 1 nM and 1 microM Ap(4)A and Ap(5)A were studied at pH 7.4, 6.5 and
      8.5. The effects of 1 microM Ap(4)A were studied during global low-flow ischaemia
      and reperfusion. 4. At pH 7.4, Ap(4)A and Ap(5)A increased action potential
      duration (APD(95)) and refractory period (RP) and reduced coronary perfusion
      pressure. The electrophysiological effects were absent at pH 6.5 while the
      reductions in perfusion pressure were attenuated. At pH 8.5, Ap(4)A increased RP
      but the effects of Ap(4)A and Ap(5)A on perfusion pressure were attenuated.
      During ischaemia, Ap(4)A had no antiarrhythmic or electrophysiological effects.
      5. These data demonstrate the importance of extracellular pH in influencing the
      effects of Ap(4)A and Ap(5)A on the heart and indicate that any potentially
      cardioprotective effects of these compounds during normal perfusion at
      physiological pH are absent during ischaemia.

PMID- 11588120
TI  - Systemic ETA receptor antagonism with BQ-123 blocks ET-1 induced forearm
      vasoconstriction and decreases peripheral vascular resistance in healthy men.
AB  - 1. The effect on systemic haemodynamics of BQ-123, a selective endothelin A (ETA)
      receptor antagonist, was investigated in healthy men by giving, on separate
      occasions, ascending intravenous doses of 100, 300, 1000 and 3000 nmol min(-1) BQ
      123, each for 15 min, in a randomized, placebo-controlled, double-blind study.
      The response of forearm blood flow to brachial artery infusion of endothelin-1
      (ET-1; 5 pmol min(-1) for 90 min) was also studied using bilateral forearm
      plethysmography, after systemic pre-treatment, on separate occasions, with one of
      two doses of BQ-123 (300 and 1000 nmol min(-1) for 15 min) or placebo. 2.
      Systemic BQ-123 dose-dependently decreased systemic vascular resistance (P<0.01
      for all doses vs placebo) and mean arterial pressure (P<0.05 for 300 nmol min(-1)
      and P<0.01 for 1000 and 3000 nmol min(-1)) during the 60 min following infusion.
      There were concurrent increases in heart rate and cardiac index. BQ-123, when
      infused systemically for 15 min, appeared to reach a maximum effect at 1000 nmol
      min(-1). 3. Intra-brachial ET-1 infusion, after pre-treatment with placebo,
      caused a slow onset progressive forearm vasoconstriction without systemic
      effects. This vasoconstriction was attenuated by pre-treatment with BQ-123 at 300
      nmol min(-1) and abolished by BQ-123 at 1000 nmol min(-1) (P<0.01 vs placebo). 4.
      These effects occurred at concentrations of BQ-123 in the plasma (510+/-64 nmol
      l(-1)) that were ETA receptor selective, and were not accompanied by an increase
      in plasma ET-1 that would have indicated ETB receptor blockade. 5. We conclude
      that ETA-mediated vascular tone contributes to the maintenance of basal systemic
      vascular resistance and blood pressure in healthy men.

PMID- 11588121
TI  - Anandamide induces cardiovascular and respiratory reflexes via vasosensory nerves
      in the anaesthetized rat.
AB  - 1. We tested the hypothesis that sensory nerves innervating blood vessels play a
      role in the local and systemic regulation of the cardiovascular and respiratory
      (CVR) systems. We measured CVR reflexes evoked by administration of anandamide
      (86 - 863 nmoles) and capsaicin (0.3 - 10 nmoles) into the hindlimb vasculature
      of anaesthetized rats. 2. Anandamide and capsaicin each caused a rapid dose
      dependent reflex fall in blood pressure and an increase in ventilation when
      injected intra-arterially into the hindlimb. 3. Action of both agonists at the
      vanilloid receptor (VR1) on perivascular sensory nerves was investigated using
      capsazepine (1 mg kg(-1) i.a.) a competitive VR1 antagonist, ruthenium red (1 mg
      kg(-1) i.a.), a non-competitive antagonist at VR1, or a desensitizing dose of
      capsaicin (200 nmoles i.a.). The cannabinoid receptor antagonist SR141716 (1 mg
      kg(-1) i.a.) was used to determine agonist activity at the CB(1) receptor. 4.
      Capsazepine, ruthenium red, or acute VR1 desensitization by capsaicin
      pretreatment, markedly attenuated the reflex CVR responses evoked by anandamide
      and capsaicin (P< 0.05; paired Student's t-test). Blockade of CB(1) had no
      significant effect on the responses to anandamide. 5. Local sectioning of the
      femoral and sciatic nerves attenuated CVR responses to anandamide and capsaicin
      (P< 0.05). Vagotomy or carotid sinus sectioning had no significant effect on
      anandamide- or capsaicin-induced responses. 6. These data demonstrate that both
      the endogenous cannabinoid, anandamide, and the vanilloid, capsaicin, evoke CVR
      reflexes when injected intra-arterially into the rat hindlimb. These responses
      appear to be mediated reflexly via VR1 located on sensory nerve endings within
      the hindlimb vasculature.

PMID- 11588122
TI  - Despite substantial degradation, 2-arachidonoylglycerol is a potent full efficacy
      agonist mediating CB(1) receptor-dependent G-protein activation in rat cerebellar
      membranes.
AB  - 1. Two endocannabinoids, arachidonoyl ethanolamide (AEA) and 2
      arachidonoylglycerol (2-AG) bind and activate G-protein-coupled cannabinoid
      receptors, but limited data exist on their relative ability to activate G
      proteins. 2. Here we assess agonist potency and efficacy of various cannabinoids,
      including 2-AG, HU-310 (2-arachidonoyl glyceryl ether, a third putative
      endocannabinoid), HU-313 (another ether analogue of 2-AG), AEA, R-methanandamide
      (an enzymatically stable analogue of AEA), and CP-55,940 at rat brain CB(1)
      receptors using agonist-stimulated [(35)S]-GTPgammaS binding to cerebellar
      membranes and whole brain sections. Degradation of endocannabinoids under
      experimental conditions was monitored by HPLC. 3. To enhance efficacy
      differences, agonist dose-response curves were generated using increasing GDP
      concentrations. At 10(-6) M GDP, all compounds, except HU-313, produced full
      agonists responses approximately 2.5 fold over basal. The superior efficacy of 2
      AG over all other compounds became evident by increasing GDP (10(-5) and 10(-4)
      M). 4. In membrane incubations, 2-AG was degraded by 85% whereas AEA and HU-310
      were stable. Pretreatment of membranes with phenylmethylsulphonyl fluoride
      inhibited 2-AG degradation, resulting in 2 fold increase in agonist potency. Such
      pretreatment had no effect on AEA potency. 5. Responses in brain sections were
      otherwise consistent with membrane binding data, but 2-AG evoked only a weak
      signal in brain sections, apparently due to more extensive degradation. 6. These
      data establish that even under conditions of substantial degradation, 2-AG is a
      full efficacy agonist, clearly more potent than AEA, in mediating CB(1) receptor
      dependent G-protein activity in native membranes.

PMID- 11588123
TI  - Effects of S-2474, a novel nonsteroidal anti-inflammatory drug, on amyloid beta
      protein-induced neuronal cell death.
AB  - 1. The accumulation of amyloid beta protein (Abeta) in the brain is a
      characteristic feature of Alzheimer's disease (AD). Clinical trials of AD
      patients with nonsteroidal anti-inflammatory drugs (NSAIDs) indicate a clinical
      benefit. NSAIDs are presumed to act by suppressing inhibiting chronic
      inflammation in the brain of AD patients. 2. In the present study, we
      investigated effects of S-2474 on Abeta-induced cell death in primary cultures of
      rat cortical neurons. 3. S-2474 is a novel NSAID, which inhibits cyclo-oxygenase
      2 (COX-2) and contains the di-tert-butylphenol antioxidant moiety. S-2474
      significantly prevented neurons from Abeta(25 - 35)- and Abeta(1 - 40)-induced
      cell death. S-2474 ameliorated Abeta-induced apoptotic features such as the
      condensation of chromatin and the fragmentation of DNA completely. 4. Prior to
      cell death, Abeta(25 - 35) generated prostaglandin D(2) (PGD(2)) and free
      radicals from neurons. PGD(2) is a product of cyclo-oxygenase (COX), and caused
      neuronal cell death. 5. S-2474 significantly inhibited the Abeta(25 - 35)-induced
      generation of PGD(2) and free radicals. 6. The present cortical cultures
      contained little non-neuronal cells, indicating that S-2474 affected neuronal
      survival directly, but not indirectly via non-neuronal cells. Both an inhibitory
      effect of COX-2 and an antioxidant effect might contribute to the neuroprotective
      effects of S-2474. 7. In conclusion, S-2474 exhibits protective effects against
      neurotoxicity of Abeta. Furthermore, the present study suggests that S-2474 may
      possess therapeutic potential for AD via ameliorating degeneration in neurons as
      well as suppressing chronic inflammation in non-neuronal cells.

PMID- 11588124
TI  - Effects of potassium channel and Na+-Ca2+ exchange blockers on the responses of
      slowly adapting pulmonary stretch receptors to hyperinflation in flecainide
      treated rats.
AB  - 1. The effects of K(+) channel blockers, such as 4-aminopyridine (4-AP) and
      tetraethylammonium (TEA), and a reverse-mode Na(+)-Ca(2+) exchange blocker, 2-[2
      [4-(4-nitrobenzyloxyl) phenyl] ethyl] isothiourea methanesulphonate (KB-R7943),
      on the responses of slowly adapting pulmonary stretch receptor activity to
      hyperinflation (inflation volume=3 tidal volumes) were investigated in
      anaesthetized, artificially ventilated, unilaterally vagotomized rats after
      pretreatment with a Na(+) channel blocker flecainide. The administration of
      flecainide (9 mg kg(-1)) at a dose greater than that which abolished 50 microg
      kg(-1) veratridine-induced SAR stimulation also inhibited hyperinflation-induced
      stimulation of SARs. 2. In flecainide-treated animals, administration of 4-AP
      (0.7 and 2 mg kg(-1)) stimulated SAR activity during normal inflation and also
      caused a partial blockade of hyperinflation-induced SAR inhibition. 3. The
      discharges of SARs during normal inflation in flecainide-treated animals were not
      significantly altered by administration of either TEA (2 and 7 mg kg(-1)) or KB
      R7943 (1 and 3 mg kg(-1)), but both K(+) channel and Na(+)-Ca(2+) exchange
      blockers partially attenuated hyperinflation-induced SAR inhibition. 4. These
      results suggest that hyperinflation-induced SAR inhibition in the presence of
      flecainide (9 mg kg(-1)) involves the activation of several K(+) conductance
      pathways.

PMID- 11588125
TI  - Modulation of serotonergic neurotransmission by short- and long-term treatments
      with sigma ligands.
AB  - 1. Sigma receptors were first described in 1976 as opiate receptors but were
      later determined to be a distinct class of receptors with two subtypes, sigma(1)
      and sigma(2). Although the endogenous ligand is yet to be elucidated, the
      sigma(1) receptor has recently been cloned. 2. Behavioural models used to test
      potential antidepressants have shown sigma ligands to produce antidepressant
      effects but their mechanism of action is unknown. 3. The goal of the present
      study was to assess the effects of various sigma(1) ligands on the firing
      activity of serotonin (5-HT) neurons of the dorsal raphe nucleus (DRN) using
      extracellular in vivo recordings in anaesthetized rats. 4. The sigma(1) ligands
      (+)-pentazocine and 4-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP) (2 mg kg(
      1) day(-1)) increased markedly 5-HT firing activity after 2 days of treatment and
      maintained the same increased firing rate after long-term (21 days) treatments.
      Furthermore, the increased firing rate produced by 2 and 21 day treatments with
      (+)-pentazocine was prevented by the co-administration of N,N-dipropyl-2-(4
      methoxy-3-(2-phenylethoxy)phenyl)-thylamine (NE-100) (10 mg kg(-1) day(-1)) a
      selective sigma(1) antagonist, confirming the sigma(1) receptor's modulation of
      these effects. In contrast, the sigma(1) ligands (+)-N-cyclopropylmethyl-N-methyl
      1,4-diphenyl-1-1-ethyl-but-3-en-1-ylamine hydrochloride (JO-1784) and 2-(4
      morpholinoethyl 1-phenyl-cyclohexane-1-carboxylate hydrochloride (PRE-084) had no
      effect. 5. Following a 21-day treatment with (+)-pentazocine there was a marked
      reduction in the number of neurons found per track. This decrease was not seen
      after chronic treatment with 4-IBP and may represent a depolarization block. 6.
      These results suggest a modulation of serotonergic neurotransmission by some
      sigma receptors and provide a potential mechanism for the 'antidepressant
      effects' reported and provide evidence toward sigma(1) ligands as potential
      antidepressants with a rapid onset of action.

PMID- 11588126
TI  - Abnormal Pap smear follow-up in a high-risk population.
AB  - Low-income women are at high risk of developing cervical cancer attributable not
      only to the higher prevalence of risk factors in this population but also to the
      lack of timely follow-up of abnormal Pap smears. This study evaluates the
      efficacy of an aggressive follow-up strategy. Women with abnormal Pap smear
      results after screening in a public hospital emergency department were randomly
      assigned to follow-up either by a case-managed approach using computerized
      tracking and universal colposcopy or by traditional care. The main outcome was
      the proportion of women receiving follow-up in 6 months. A secondary outcome was
      the proportion of women receiving follow-up by 6 months and diagnostic resolution
      in 18 months. Of 54 women in the intervention group, 65% kept at least one follow
      up appointment in 6 months compared with 41% of the 54 women in the control group
      (P = 0.012). Half the women in the intervention group versus 19% of women in the
      control group had follow-up in 6 months and diagnostic resolution in 18 months (P
      = 0.001). After adjusting for age, initial Pap smear result, and race/ethnicity,
      the odds of having follow-up in 6 months were four times greater for women in the
      intervention group (odds ratio = 4.0; 95% confidence interval, 1.6-9.7), and the
      odds of having both follow-up in 6 months and diagnostic resolution in 18 months
      were more than six times greater (odds ratio = 6.5; 95% confidence interval, 2.4
      17.8). This study demonstrates that an aggressive follow-up strategy
      significantly improves the rate of both initial follow-up and diagnostic
      resolution of abnormal Pap smears among low-income women with atypical squamous
      cells of undetermined significance and atypical glandular cells of undetermined
      significance when compared with traditional care.

PMID- 11588127
TI  - An association of cervical inflammation with high-grade cervical neoplasia in
      women infected with oncogenic human papillomavirus (HPV).
AB  - Previous reports of genital conditions, such as nonspecific genital
      infection/sore or vaginal discharge associated with cervical cancer (L. A.
      Brinton et al., J. Natl. Cancer Inst. (Bethesda), 79: 23-30, 1987; C. J. Jones et
      al., Cancer Res., 50: 3657-3662, 1990), suggest a possible link between either
      genital tract inflammation or changes in bacteria flora consistent with bacterial
      vaginosis (BV) and cervical cancer. To test whether changes in vaginal bacterial
      flora or the degree of cervical inflammation are associated with women having a
      human papillomavirus (HPV) infection or with women infected with oncogenic HPV
      having high-grade cervical lesions (high-grade squamous intraepithelial lesions
      or cancer), we conducted a case-control study of women <50 years old enrolled in
      the Costa Rican natural history study of HPV and cervical neoplasia. To test
      whether BV and inflammation were associated with HPV DNA positivity, Analysis 1
      was restricted to women with no or mild (low-grade or equivocal) cytological
      abnormalities, and the degree of inflammation and Nugent score (a measure of BV)
      were compared between women infected (n = 220) and not infected (n = 130) with
      HPV. To test whether BV and inflammation were associated with high-grade lesions,
      Analysis 2 was restricted to women infected with oncogenic HPV, and the degree of
      inflammation and Nugent score were compared between women with (n = 95) and
      without (n = 158) high-grade cervical lesions. In Analysis 1, BV and cervical
      inflammation were not associated with HPV infection. In Analysis 2, BV was not
      associated with high-grade lesions. However, we found a marginally significant
      positive trend of increasing cervical inflammation associated with high-grade
      lesions in oncogenic HPV-infected women, (P(trend) = 0.05). Overt cervicitis was
      associated with a 1.9-fold increase in risk of high-grade lesions (95% confidence
      interval, 0.90-4.1). The results of this study suggest that cervical inflammation
      may be associated with high-grade lesions and may be a cofactor for high-grade
      cervical lesions in women infected with oncogenic HPV.

PMID- 11588128
TI  - A randomized, double blind, Phase III trial using oral beta-carotene
      supplementation for women with high-grade cervical intraepithelial neoplasia.
AB  - To evaluate the effect of daily beta-carotene (30 mg) versus placebo over a 2
      year period on cervical intraepithelial neoplasia (CIN) 2 and 3 lesions. Human
      papillomavirus (HPV) typing was done to determine whether lesion regression was
      related to HPV. Micronutrient levels were measured to determine whether levels
      were predictive of regression. Variables that influence the risk of HPV infection
      and CIN, such as cigarette smoking and sexual behavior, were evaluated. Women
      were randomized to beta-carotene or placebo, with cytology and colposcopy every 3
      months. Cervical biopsies were performed before treatment and after 6 and 24
      months to evaluate response. Persistence of or progression to CIN 3 resulted in
      removal from the study, whereas treatment continued for 2 years on all others.
      The presence and type of HPV was determined by PCR. Response was defined as an
      improvement in CIN by 2 grades. Mantel-Haenszel chi(2) test was used to analyze
      response to treatment. Fisher's exact test was used to determine the effect of
      HPV and CIN grade on response Wilcoxon's rank-sum tests were used to compare
      micronutrient levels between groups. Twenty-one of 124 enrolled women were not
      randomized because they either moved, became pregnant, voluntarily withdrew, or
      the pathological review of their initial cervical biopsies did not confirm CIN 2
      or 3. Of the remaining 103 women, 33 experienced lesion regression, 45 had
      persistent or progressive disease, and 25 women did not complete the study and
      were considered nonresponders in the final analysis. The overall regression rate
      (32%) was similar between treatment arms and when stratified for CIN grade. Data
      on 99 women with HPV typing showed that 77% were HPV-positive and 23% HPV
      negative at enrollment. HPV-positive lesions were subdivided into indeterminate-,
      low-, and high-risk categories; the response rate was highest for women with no
      HPV detected (61%), lower for indeterminate/low-risk (30%), and lowest for high
      risk (18%; P =.001). CIN regression was negatively correlated with retinol
      levels. In conclusion, beta-carotene does not enhance the regression of high
      grade CIN, especially in HPV-positive subjects.

PMID- 11588129
TI  - HLA class II DR-DQ and increased risk of cervical cancer among Senegalese women.
AB  - To examine Senegalese women to confirm and extend associations between HLA class
      II types and cervical cancer previously observed among African-American,
      Caucasian, Hispanic, and Japanese ethnic populations, 55 Senegalese women with
      invasive cervical carcinoma were compared with age-matched (human papillomavirus)
      HPV-positive (n = 83) and HPV-negative (n = 107) control women. PCR-based HPV and
      HLA typing methods were used. Data were analyzed using a global randomization
      test and conditional logistic regression. Although this study failed to confirm a
      previously reported association between cervical cancer and DQB1*03 alleles, the
      DRB1*1101-DQB1*0301 haplotype was detected more frequently among cervical
      carcinoma cases than among controls (adjusted odds ratio, 2.6; 95% confidence
      interval, 1.0-7.1). Furthermore, as reported by others, we observed a negative
      association of borderline statistical significance between DRB1*13 and cervical
      carcinoma (adjusted odds ratio, 0.5; 95% confidence interval, 0.2-1.1).
      Observations from this study confirm earlier findings of a negative association
      between DRB1*13 and cervical cancer and suggest that specific DRB1-DQB1 haplotype
      combinations, rather than individual DQB1*03 alleles, increase the risk for
      cervical cancer.

PMID- 11588130
TI  - Long-term effects of fenretinide, a retinoic acid derivative, on the insulin-like
      growth factor system in women with early breast cancer.
AB  - High insulin-like growth factor-I (IGF-I) levels are associated with an increased
      risk of breast cancer in premenopausal women. Because the synthetic retinoid
      fenretinide showed a beneficial effect on second breast cancers in premenopausal
      women in a Phase III trial, we studied its long-term effects on IGF-I levels. We
      measured, at yearly intervals for up to 5 years, the circulating levels of IGF-I,
      IGF binding protein (BP)-3, and their molar ratio in 60 subjects < or = 50 years
      of age and 60 subjects > 50 years of age allocated either to fenretinide or no
      treatment. In women < or = 50 years of age, measurements of IGF-II, IGFBP-1, and
      IGFBP-2 were also performed. The associations between biomarkers and drug or
      metabolite plasma concentrations were also investigated. All biomarkers were
      relatively stable over 5 years in the control group. Compared with controls and
      after adjustment for baseline, treatment with fenretinide for 1 year induced the
      following changes: IGF-I, -13% [95% confidence interval (CI), -25 to 1%] in women
      < or = 50 years of age and -3% (95% CI, -16 to 13%) in women > 50 years of age;
      IGFBP-3, -4% (95% CI, -12 to 6%) in both age groups; IGF-I:IGFBP-3 molar ratio, 
      11% (95% CI, -22 to 1%) in women < or = 50 years of age and 1% (95% CI, -11 to
      16%) in women > 50 years of age. These effects were apparently maintained for up
      to 5 years, although fewer samples were available as time progressed. No change
      in other IGF components was observed. Drug and metabolite concentrations were
      negatively correlated with IGF-I and IGF-I:IGFBP-3 molar ratio in women < or = 50
      years of age. Fenretinide induces a moderate decline of IGF-I levels in women <
      or = 50 years of age. The association between IGF-I change and the reduction of
      second breast cancers in premenopausal women warrants further study.

PMID- 11588131
TI  - Nutrient intake and risk of subtypes of esophageal and gastric cancer.
AB  - Incidence rates for adenocarcinoma of the esophagus and gastric cardia have been
      rising rapidly. We examined nutrient intake as a risk factor for esophageal and
      gastric cancers in a population-based case-control study in Connecticut, New
      Jersey, and western Washington state. Interviews were completed for cases with
      histologically confirmed esophageal adenocarcinoma (n = 282), adenocarcinoma of
      the gastric cardia (n = 255), esophageal squamous cell carcinoma (n = 206), and
      noncardia gastric adenocarcinoma (n = 352), along with population controls (n =
      687). Associations between nutrient intake and risk of cancer were estimated by
      adjusted odds ratios (ORs), comparing the 75th versus the 25th percentile of
      intake. The following nutrients were significantly inversely associated with risk
      of all four tumor types: fiber, beta-carotene, folate, and vitamins C and B6. In
      contrast, dietary cholesterol, animal protein, and vitamin B12 were significantly
      positively associated with risk of all four tumor types. Dietary fat [OR, 2.18;
      95% confidence interval (CI), 1.27-3.76] was significantly associated with risk
      of esophageal adenocarcinoma only. Dietary nitrite (OR, 1.65; 95% CI, 1.26-2.16)
      was associated with noncardia gastric cancer only. Vitamin C supplement use was
      associated with a significantly lower risk for noncardia gastric cancer (OR,
      0.60; 95% CI, 0.41-0.88). Higher intake of nutrients found primarily in plant
      based foods was associated with a reduced risk of adenocarcinomas of the
      esophagus and gastric cardia, whereas higher intake of nutrients found primarily
      in foods of animal origin was associated with an increased risk.

PMID- 11588132
TI  - Dietary isothiocyanates, glutathione S-transferase -M1, -T1 polymorphisms and
      lung cancer risk among Chinese women in Singapore.
AB  - Chinese populations consume a diet relatively high in isothiocyanates (ITCs), a
      derivative of cruciferous vegetables known to have cancer-protective effects.
      This class of compounds is metabolized by the glutathione S-transferase family of
      enzymes, which are also involved in the detoxification of tobacco-related
      carcinogens such as polycyclic aromatic hydrocarbons and alkyl halides. We
      evaluated the association between dietary isothiocyanate intake, GSTM1 and GSTT1
      polymorphisms, and lung cancer risk in 420 Chinese women: 233 histologically
      confirmed lung cancer patients and 187 hospital controls. Among these, 58.8% of
      cases and 90.3% of controls were lifetime nonsmokers. An allele-specific PCR
      method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in
      DNA isolated from peripheral blood. Higher weekly intake of ITCs (above the
      control median value of 53.0 micromol) reduced the risk of lung cancer to a
      greater extent in smokers [adjusted odds ratio (OR), 0.31; 95% confidence
      interval (CI), 0.10-0.98] than nonsmokers (OR, 0.70; 95% CI, 0.45-1.11). The
      inverse association was stronger among subjects with homozygous deletion of GSTM1
      and/or GSTT1. Among nonsmokers with GSTM1-null genotype, higher intake of ITCs
      significantly reduced the risk of lung cancer (OR, 0.54; 95% CI, 0.30-0.95), an
      effect not seen among those with detectable GSTM1 (OR, 1.07; 95% CI, 0.50-2.29).
      Our results, in a Chinese female population, are consistent with the hypothesis
      that ITC is inversely related to the risk of lung cancer, and we show that among
      nonsmokers this effect may be primarily confined to GST-null individuals.
      Conjugation and elimination of ITCs is enhanced in GST-non-null relative to -null
      individuals, such that the GST metabolic genotype modifies the protective effect
      of ITCs on lung cancer development.

PMID- 11588133
TI  - Predictors of serum selenium in cigarette smokers and the lack of association
      with lung and prostate cancer risk.
AB  - Epidemiological studies have suggested that low levels of selenium are associated
      with a higher incidence of both lung and prostate cancer. We analyzed the
      selenium serum concentration in 356 Carotene and Retinol Efficacy Trial (CARET)
      participants who later developed lung cancer and 356 matched controls and in 235
      prostate cancer cases and 456 matched controls. Serum samples were obtained a
      mean of 4.7 years before diagnosis for both tumor types. Controls were matched to
      cases by year of randomization, age, smoking status, treatment arm, exposure
      population (asbestos workers or cigarette smokers), and year of blood draw. In
      the control population (n = 820), significant predictors of low serum selenium
      concentration were current smoking status and East Coast locations of the study
      center. Overall, there was no significant difference in mean serum selenium in
      lung cancer cases versus controls (11.91 microg/dl versus 11.77 microg/dl) or
      prostate cancer cases versus controls (11.48 microg/dl versus 11.43 microg/dl).
      No statistically significant trend in odds ratio was seen across quartiles of
      serum selenium for lung cancer (P = 0.49) or prostate cancer (P = 0.69). In a
      subpopulation of 174 prostate cancer patients who had clinical and pathological
      staging material reviewed, there was no association between serum selenium and
      Gleason score or clinical or pathological stage. In the CARET population of
      current and former smokers consuming an ad libitum diet, the serum concentration
      of selenium was not a risk factor for either lung cancer or prostate cancer.

PMID- 11588134
TI  - Polymorphic markers in the SRD5A2 gene and prostate cancer risk: a population
      based case-control study.
AB  - It has been suggested that the activity of the steroid 5alpha-reductase type II
      enzyme (encoded by the SRD5A2 gene) may be associated with prostate cancer risk
      and that population differences in this enzyme's activity may account for part of
      the substantial racial/ethnic disparity in prostate cancer risk. To provide
      etiological clues, we evaluated the relationships of four polymorphic markers in
      the SRD5A2 gene, specifically, A49T (a substitution of threonine for alanine at
      codon 49), V89L (a substitution of leucine for valine at codon 89), R227Q (a
      substitution of glutamine for arginine at codon 227), and a (TA)n dinucleotide
      repeat, with prostate cancer risk in a population-based case-control study in
      China, a population with the lowest reported prostate cancer incidence rate in
      the world. Genotypes of these four markers were determined from genomic DNA of
      191 incident cases of prostate cancer and 304 healthy controls using PCR-based
      assays, and serum androgen levels were measured in relation to these genotypes.
      All study subjects had the wild-type AA genotype of the A49T marker, and 99% had
      the RR genotype of the R227Q marker. For the V89L marker, prevalences of the LL,
      VV, and VL genotypes among controls were 35%, 21%, and 45%, respectively.
      Compared with men with the VV genotype, those with the LL genotype had a
      statistically nonsignificant 12% reduced risk (odds ratio = 0.88, 95% confidence
      interval, 0.53-1.47). In addition, men with the LL genotype had significantly
      higher serum levels of testosterone and significantly lower serum levels of
      5alpha-androstane-3alpha,17beta-diol glucuronide than men with other genotypes.
      Men heterozygous for the (TA)0 allele of the (TA)n marker had a modest,
      statistically nonsignificant risk reduction (odds ratio = 0.67; 95% confidence
      interval, 0.39-1.12) compared with men homozygous for the (TA)0 allele, along
      with significantly higher serum dihydrotestosterone levels. The observed V89L
      genotype prevalences and the association between V89L genotypes and serum
      androgen levels support the hypothesis that genotypes associated with lower
      levels of 5alpha-reductase activity are more common in low-risk populations.
      Although we found no statistically significant associations of these SRD5A2
      polymorphisms with prostate cancer risk, a small effect of these markers cannot
      be ruled out because of the rarity of certain marker genotypes. Larger studies
      are needed to further clarify the role of these markers and to elucidate whether
      genetic diversity of the SRD5A2 gene, alone or in combination with other
      susceptibility genes, can help explain the large racial/ethnic differences in
      prostate cancer risk.

PMID- 11588135
TI  - Tannic acid potently inhibits tumor cell proteasome activity, increases p27 and
      Bax expression, and induces G1 arrest and apoptosis.
AB  - Animal studies have demonstrated that a dietary polyphenol known as tannic acid
      (TA) exhibits anticarcinogenic activity in chemically induced cancers, although
      the involved molecular target remains unknown. In addition, proteasome inhibitors
      have been shown to suppress human tumor growth in nude mice. Most recently, we
      have reported that ester-bond-containing tea polyphenols are potent proteasome
      inhibitors in vitro and in vivo. We have hypothesized that TA, which contains
      multiple similar gallate moieties linked by ester bonds, should inhibit the
      proteasome activity. Here, we report that indeed TA potently and specifically
      inhibits the chymotrypsin-like activity of purified 20S proteasome (IC(50) = 0.06
      microg/ml), 26S proteasome of Jurkat T-cell extracts, and 26S proteasome of
      living Jurkat cells. Inhibition of the proteasome by TA in Jurkat cells results
      in accumulation of two natural proteasome substrates, the cyclin-dependent kinase
      inhibitor p27(Kip1) and the proapoptotic protein Bax, followed by growth arrest
      in G1 and induction of apoptotic cell death. Our present study suggests that TA
      targets and inhibits the proteasome in tumor cells, which may contribute to the
      previously observed anticarcinogenic activity of TA.

PMID- 11588136
TI  - The effect of folic acid deficiency and MTHFR C677T polymorphism on chromosome
      damage in human lymphocytes in vitro.
AB  - We performed a comprehensive study on the genotoxic and cytotoxic effects of in
      vitro folic acid deficiency on primary human lymphocytes. Lymphocytes were
      cultured in medium containing 12-120 nM folic acid for 9 days in a novel
      cytokinesis-block micronucleus (CBMN) assay system (n = 20). Besides identifying
      optimal folic acid concentrations for in vitro genomic stability, we tested the
      hypothesis that lymphocytes from individuals homozygous for the C677T
      methylenetetrahydrofolate reductase (MTHFR) polymorphism (TTs, n = 10) are
      protected against chromosome damage relative to controls (CCs, n = 10) under
      conditions of folic acid deficiency. This hypothesis is based on the assumption
      that reduced MTHFR activity in TT lymphocytes causes a diversion of 5,10
      methylene tetrahydrofolate toward thymidine synthesis, which minimizes uracil
      induced double-stranded DNA breakage. Cells were scored for micronuclei,
      apoptosis, necrosis, nucleoplasmic bridges, and nuclear budding. The latter two
      endpoints are indicative of chromosome rearrangements and gene amplification,
      respectively, and to the best of our knowledge, this is the first report of their
      association with folic acid concentration. Folic acid concentration correlated
      significantly (P < 0.0001) and negatively (r, -0.63 to -0.74) with all markers of
      chromosome damage, which were minimized at 60-120 nM folic acid, much greater
      than concentrations assumed "normal," but not necessarily optimal in plasma. Two
      way ANOVA revealed no effect of the MTHFR genotype on any of the endpoints.
      Results show that the C677T polymorphism does not affect the ability of a cell to
      resist chromosome damage induced by folic acid deficiency in this in vitro
      system.

PMID- 11588137
TI  - Perceptions of informed consent by participants in a prostate cancer prevention
      study.
AB  - This study examined perceptions of the informed consent process in healthy men
      participating in a cancer prevention clinical trial. Specifically, we examined
      influence of the consent form on participation and understanding, adequacy of the
      consent process in preparing participants for trial experiences, and perceived
      needs for additional follow-up strategies. Participants (n = 69) enrolled in the
      Prostate Cancer Prevention Trial at our institution completed mailed
      questionnaires approximately 2 years after joining the study. Results indicated
      that many participants had no remembrance of the consent process, and only a
      minority reported that the consent process had helped in decision-making about
      study participation. Eleven men (16%) reported experiencing unexpected study side
      effects, most related to sexual functioning. Most men (78%) did not feel that
      they currently needed more information about the study, although virtually all of
      the respondents wanted to learn the study results. Almost one-third wished to
      interact with other Prostate Cancer Prevention Trial participants. Results
      indicate that a signed consent form and initial counseling for a prevention study
      does not ensure that participants feel they are adequately informed about the
      study or the side effects. Providing and reinforcing information on a regular and
      continuous basis is especially important in studies where compliance is required
      over a period of years.

PMID- 11588138
TI  - Null association between insulin-like growth factors, insulin-like growth factor
      binding proteins, and prostate cancer in a prospective study.

PMID- 11588139
TI  - Correspondence re: Giovannucci et al., A prospective study of plasma insulin-like
      growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women.
      Cancer Epidemiol. Biomark. Prev., 9: 345-349, 2000.

PMID- 11588140
TI  - Re: Spitz, M. R., Duphorne, C. M., Detry, M. A., Pillow, P. C., Amos, C. I., Lei,
      L., de Andrade, M., Gu, X., Hong, W. K., and Wu, X. Dietary intake of
      isothiocyanates: evidence of a joint effect with glutathione S-transferase
      polymorphisms in lung cancer risk. Cancer Epidemiol. Biomark. Prev., 9: 1017
      1020, 2000.

PMID- 11588141
TI  - Mechanisms and physiological significance of the cholinergic control of
      pancreatic beta-cell function.
AB  - Acetylcholine (ACh), the major parasympathetic neurotransmitter, is released by
      intrapancreatic nerve endings during the preabsorptive and absorptive phases of
      feeding. In beta-cells, ACh binds to muscarinic M(3) receptors and exerts complex
      effects, which culminate in an increase of glucose (nutrient)-induced insulin
      secretion. Activation of PLC generates diacylglycerol. Activation of PLA(2)
      produces arachidonic acid and lysophosphatidylcholine. These phospholipid-derived
      messengers, particularly diacylglycerol, activate PKC, thereby increasing the
      efficiency of free cytosolic Ca(2+) concentration ([Ca(2+)](c)) on exocytosis of
      insulin granules. IP3, also produced by PLC, causes a rapid elevation of
      [Ca(2+)](c) by mobilizing Ca(2+) from the endoplasmic reticulum; the resulting
      fall in Ca(2+) in the organelle produces a small capacitative Ca(2+) entry. ACh
      also depolarizes the plasma membrane of beta-cells by a Na(+)- dependent
      mechanism. When the plasma membrane is already depolarized by secretagogues such
      as glucose, this additional depolarization induces a sustained increase in
      [Ca(2+)](c). Surprisingly, ACh can also inhibit voltage-dependent Ca(2+) channels
      and stimulate Ca(2+) efflux when [Ca(2+)](c) is elevated. However, under
      physiological conditions, the net effect of ACh on [Ca(2+)](c) is always
      positive. The insulinotropic effect of ACh results from two mechanisms: one
      involves a rise in [Ca(2+)](c) and the other involves a marked, PKC-mediated
      increase in the efficiency of Ca(2+) on exocytosis. The paper also discusses the
      mechanisms explaining the glucose dependence of the effects of ACh on insulin
      release.

PMID- 11588143
TI  - Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age:
      recent insights and consequences for antenatal and postnatal care.
AB  - Postpartum thyroiditis is a syndrome of transient or permanent thyroid
      dysfunction occurring in the first year after delivery and based on an autoimmune
      inflammation of the thyroid. The prevalence ranges from 5-7%. We discuss the role
      of antibodies (especially thyroid peroxidase antibodies), complement, activated T
      cells, and apoptosis in the outbreak of postpartum thyroiditis. Postpartum
      thyroiditis is conceptualized as an acute phase of autoimmune thyroid destruction
      in the context of an existing and ongoing process of thyroid autosensitization.
      From pregnancy an enhanced state of immune tolerance ensues. A rebound reaction
      to this pregnancy-associated immune suppression after delivery explains the
      aggravation of autoimmune syndromes in the puerperal period, e.g., the occurrence
      of clinically overt postpartum thyroiditis. Low thyroid reserve due to autoimmune
      thyroiditis is increasingly recognized as a serious health problem. 1) Thyroid
      autoimmunity increases the probability of spontaneous fetal loss. 2) Thyroid
      failure due to autoimmune thyroiditis-often mild and subclinical-can lead to
      permanent and significant impairment in neuropsychological performance of the
      offspring. 3) Evidence is emerging that as women age subclinical hypothyroidism
      as a sequel of postpartum thyroiditis-predisposes them to cardiovascular disease.
      Hence, postpartum thyroiditis is no longer considered a mild and transient
      disorder. Screening is considered.

PMID- 11588145
TI  - Regulation of thyroid cell proliferation by TSH and other factors: a critical
      evaluation of in vitro models.
AB  - TSH via cAMP, and various growth factors, in cooperation with insulin or IGF-I
      stimulate cell cycle progression and proliferation in various thyrocyte culture
      systems, including rat thyroid cell lines (FRTL-5, WRT, PC Cl3) and primary
      cultures of rat, dog, sheep and human thyroid. The available data on cell
      signaling cascades, cell cycle kinetics, and cell cycle-regulatory proteins are
      thoroughly and critically reviewed in these experimental systems. In most FRTL-5
      cells, TSH (cAMP) merely acts as a priming/competence factor amplifying PI3K and
      MAPK pathway activation and DNA synthesis elicited by insulin/IGF-I. In WRT
      cells, TSH and insulin/IGF-I can independently activate Ras and PI3K pathways and
      DNA synthesis. In dog thyroid primary cultures, TSH (cAMP) does not activate Ras
      and PI3K, and cAMP must be continuously elevated by TSH to directly control the
      progression through G(1) phase. This effect is exerted, at least in part, via the
      cAMP-dependent activation of the required cyclin D3, itself synthesized in
      response to insulin/IGF-I. This and other discrepancies show that the mechanistic
      logics of cell cycle stimulation by cAMP profoundly diverge in these different in
      vitro models of the same cell. Therefore, although these different thyrocyte
      systems constitute interesting models of the wide diversity of possible
      mechanisms of cAMP-dependent proliferation in various cell types, extrapolation
      of in vitro mechanistic data to TSH-dependent goitrogenesis in man can only be
      accepted in the cases where independent validation is provided.

PMID- 11588147
TI  - Mullerian inhibiting substance: an instructive developmental hormone with
      diagnostic and possible therapeutic applications.
AB  - Dr. Alfred Jost pioneered the field of reproductive endocrinology with his
      seminal observation that two hormones produced by the testes are required for the
      male embryo to develop a normal internal reproductive tract. T induces the
      Wolffian ducts to differentiate into epididymides, vasa deferens, and seminal
      vesicles. Mullerian inhibiting substance (MIS) causes regression of the Mullerian
      ducts, which in its absence would normally develop into the Fallopian tubes,
      uterus, and upper vagina as is observed in female embryos. This review will
      summarize our current understanding of molecular mechanisms underlying the
      function of MIS both as a fetal gonadal hormone that causes Mullerian duct
      regression and as an adult hormone, the roles for which are currently being
      investigated, i.e., inhibition of steroidogenesis, germ cell development, and
      cancer. We will also address the regulation of MIS expression as one of the first
      genes expressed after the commitment of the bipotential gonads to differentiate
      into testes under the influence of SRY, the gene on the sex-determining region of
      the Y chromosome. We will discuss what is known regarding MIS signal
      transduction, which as with other members of the TGFbeta family of growth and
      differentiation factors, occurs through a heteromeric complex of single
      transmembrane serine/threonine kinase receptors to effect downstream signaling
      events, including Smad, nuclear factor-kappaB, beta-catenin, and p16 activation.
      Finally, we will assess the clinical relevance of studying MIS in patients with
      persistent Mullerian duct syndrome and our efforts to determine the therapeutic
      value of MIS for patients with ovarian and other MIS receptor-expressing cancers.

PMID- 11588148
TI  - Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the
      role of genomic imprinting.
AB  - The heterotrimeric G protein G(s) couples hormone receptors (as well as other
      receptors) to the effector enzyme adenylyl cyclase and is therefore required for
      hormone-stimulated intracellular cAMP generation. Receptors activate G(s) by
      promoting exchange of GTP for GDP on the G(s) alpha-subunit (G(s)alpha) while an
      intrinsic GTPase activity of G(s)alpha that hydrolyzes bound GTP to GDP leads to
      deactivation. Mutations of specific G(s)alpha residues (Arg(201) or Gln(227))
      that are critical for the GTPase reaction lead to constitutive activation of G(s)
      coupled signaling pathways, and such somatic mutations are found in endocrine
      tumors, fibrous dysplasia of bone, and the McCune-Albright syndrome. Conversely,
      heterozygous loss-of-function mutations may lead to Albright hereditary
      osteodystrophy (AHO), a disease characterized by short stature, obesity,
      brachydactyly, sc ossifications, and mental deficits. Similar mutations are also
      associated with progressive osseous heteroplasia. Interestingly, paternal
      transmission of GNAS1 mutations leads to the AHO phenotype alone
      (pseudopseudohypoparathyroidism), while maternal transmission leads to AHO plus
      resistance to several hormones (e.g., PTH, TSH) that activate G(s) in their
      target tissues (pseudohypoparathyroidism type IA). Studies in G(s)alpha knockout
      mice demonstrate that G(s)alpha is imprinted in a tissue-specific manner, being
      expressed primarily from the maternal allele in some tissues (e.g., renal
      proximal tubule, the major site of renal PTH action), while being biallelically
      expressed in most other tissues. Disrupting mutations in the maternal allele lead
      to loss of G(s)alpha expression in proximal tubules and therefore loss of PTH
      action in the kidney, while mutations in the paternal allele have little effect
      on G(s)alpha expression or PTH action. G(s)alpha has recently been shown to be
      also imprinted in human pituitary glands. The G(s)alpha gene GNAS1 (as well as
      its murine ortholog Gnas) has at least four alternative promoters and first
      exons, leading to the production of alternative gene products including
      G(s)alpha, XLalphas (a novel G(s)alpha isoform that is expressed only from the
      paternal allele), and NESP55 (a chromogranin-like protein that is expressed only
      from the maternal allele). A fourth alternative promoter and first exon (exon 1A)
      located approximately 2.5 kb upstream of the G(s)alpha promoter is normally
      methylated on the maternal allele and transcriptionally active on the paternal
      allele. In patients with isolated renal resistance to PTH
      (pseudohypoparathyroidism type IB), the exon 1A promoter region has a paternal
      specific imprinting pattern on both alleles (unmethylated, transcriptionally
      active), suggesting that this region is critical for the tissue-specific
      imprinting of G(s)alpha. The GNAS1 imprinting defect in pseudohypoparathyroidism
      type IB is predicted to decrease G(s)alpha expression in renal proximal tubules.
      Studies in G(s)alpha knockout mice also demonstrate that this gene is critical in
      the regulation of lipid and glucose metabolism.

PMID- 11588149
TI  - Recombinant DNA technology in the treatment of diabetes: insulin analogs.
AB  - After more than half a century of treating diabetics with animal insulins,
      recombinant DNA technologies and advanced protein chemistry made human insulin
      preparations available in the early 1980s. As the next step, over the last
      decade, insulin analogs were constructed by changing the structure of the native
      protein with the goal of improving the therapeutic properties of it, because the
      pharmacokinetic characteristics of rapid-, intermediate-, and long-acting
      preparations of human insulin make it almost impossible to achieve sustained
      normoglycemia. The first clinically available insulin analog, lispro, confirmed
      the hopes by showing that improved glycemic control can be achieved without an
      increase in hypoglycemic events. Two new insulin analogs, insulin glargine and
      insulin aspart, have recently been approved for clinical use in the United
      States, and several other analogs are being intensively tested. Thus, it appears
      that a rapid acceleration of basic and clinical research in this arena will be
      seen, which will have direct significance to both patients and their physicians.
      The introduction of new short-acting analogs and the development of the first
      truly long-acting analogs and the development of analogs with increased
      stability, less variability, and perhaps selective action, will help to develop
      more individualized treatment strategies targeted to specific patient
      characteristics and to achieve further improvements in glycemic control. Data on
      the currently available and tested analogs, as well as data on those currently
      being developed, are reviewed.

PMID- 11588151
TI  - The endocrine society and pharmacia corporation award for published clinical
      research in the journal of clinical endocrinology & metabolism.

PMID- 11588152
TI  - Genetically modified animals in endocrinology.

PMID- 11588153
TI  - Fucosyltransferases: structure/function studies.
AB  - Alpha3-fucosyltransferases (alpha3-FucTs) catalyze the final step in the
      synthesis of a range of important glycoconjugates that function in cell adhesion
      and lymphocyte recirculation. Six members of this family of enzymes have been
      cloned from the human genome, and their expression pattern has been shown to be
      highly regulated. Each enzyme has a unique acceptor substrate binding pattern,
      and each generates a unique range of fucosylated products. Results from a range
      of studies have provided information on amino acids in the FucT sequence that
      contribute to the differential acceptor specificity for the FucTs, and to the
      binding of the nucleotide sugar donor GDP-fucose. These results, in conjunction
      with results obtained from the analysis of the disulfide bond pattern, have
      provided useful clues about the spatial distribution of amino acids that
      influence or directly contribute to substrate binding. This information is
      reviewed here, and a molecular fold prediction is presented which has been
      constructed based on the available information and current modeling methodology.

PMID- 11588154
TI  - Keratan sulfate disaccharide composition determined by FACE analysis of
      keratanase II and endo-beta-galactosidase digestion products.
AB  - Many tissues contain glycoproteins and proteoglycans, which are substituted with
      N-or O-linked keratan sulfate, a glycosaminoglycan in which the lactosamine (
      galbeta1,4glcNAc-) disaccharide backbone is variably modified by sulfation,
      fucosylation, and sialylation. We report here a rapid, sensitive, and
      quantitative procedure for obtaining a complete disaccharide compositional
      analyses for keratan sulfates after FACE separation of products generated by
      hydrolysis of the glycosaminoglycans with B. fragillis keratanase II and E.
      freundii endo-beta-galactosidase. Seven digestion end products are separable in a
      single electrophoretic step using Monosaccharide composition gels. These are: the
      unsulfated disaccharide, glcNAcbeta1,3gal, the fucosylated trisaccharide,
      galbeta1,2[fucalpha1,3]glcNAc6S, the mono- and disulfated disaccharides,
      galbeta1,4glcNAc6S or gal6Sbeta1,4glcNAc6S from the chain interior, and the
      sialylated mono- and disulfated trisaccharides neuAalpha2,3galbeta1,4glcNAc6S or
      neuAalpha2,3gal6Sbeta1,4glcNAc6S from the nonreducing terminus. FACE analyses
      also revealed the presence of a contaminant beta-galactosidase activity in
      keratanase II enzyme preparations which cleaves the disaccharide,
      galbeta1,4glcNAc6S to its constituent monosaccharides, gal and glcNAc6S. It was
      particularly prominent at enzyme concentrations > 2 mU per nmole substrate
      glcNH(2) or after prolonged digestion times (> 12 h), and was not inhibitable by
      thiogalactosides or N-acetyl-lactosamine. As these monosaccharide products would
      not be detectable using the commonly described analytical methods for KS
      hydrolase products, such as (1)H-NMR and HPLC analyses, our data illustrate that
      the FACE procedure represents an improved approach for accurate compositional
      microanalyses of corneal and skeletal keratan sulfates, especially applicable to
      experimentation involving small amounts (1-2 microg) of this glycosaminoglycan.

PMID- 11588155
TI  - Characterization of human apolipoprotein B100 oligosaccharides in LDL
      subfractions derived from normal and hyperlipidemic plasma: deficiency of alpha-N
      acetylneuraminyllactosyl-ceramide in light and small dense LDL particles.
AB  - The carbohydrate composition of apolipoprotein (apo) B100, particularly its
      degree of sialylation, may contribute to the atherogenic properties of low
      density lipoprotein (LDL). We analyzed LDL apoB100 glycans derived from
      normolipidemic, hypercholesterolemic, and hypertriglyceridemic diabetic subjects.
      Using exoglycosidase carbohydrate sequencing and matrix-assisted laser
      desorption/ionization mass spectrometry to analyze fluorescently labeled
      oligosaccharides, we report evidence for several carbohydrates not previously
      identified on apoB100, including truncated complex biantennary N-glycans and
      hybrid N-glycans. The distribution and diversity of the apoB100 glycans isolated
      from all individuals was highly conserved. The N-glycan composition of apoB100
      derived from five LDL subpopulations (LDL1, d = 1.018-1.023; LDL2, d = 1.023
      1.030; LDL3, d = 1.030-1.040; LDL4, d = 1.040-1.051; LDL5, d = 1.051-1.065 g/ml)
      did not vary in normolipidemic or hypercholesterolemic subjects. Furthermore, we
      found no evidence for "desialylated" apoB100 glycans in any of the samples
      analyzed. Analysis of the most abundant LDL ganglioside, alpha-N
      acetylneuraminyllactosyl-ceramide, revealed a deficiency in small dense LDL and
      in the most buoyant subpopulation. These data provide a novel explanation for the
      apparent deficiency of sialic acid in small dense LDL and indicate that the
      global apoB100 N-glycan composition is invariable in the patient groups studied.

PMID- 11588156
TI  - Release of polymannose oligosaccharides from vesicular stomatitis virus G protein
      during endoplasmic reticulum-associated degradation.
AB  - To further explore the localization of the N-deglycosylation involved in the
      endoplasmic reticulum (ER)-associated quality control system we studied HepG2
      cells infected with vesicular stomatitis virus (VSV) and its ts045 mutant, as in
      this system oligosaccharide release can be attributed solely to the VSV
      glycoprotein (G protein). We utilized the restricted intracellular migration of
      the mutant protein as well as dithiothreitol (DTT), low temperature, and a
      castanospermine (CST)-imposed glucosidase blockade to determine in which
      intracellular compartment deglycosylation takes place. Degradation of the VSV
      ts045 G protein was considerably greater at the nonpermissive than at the
      permissive temperature; this was reflected by a substantial increase in
      polymannose oligosaccharide release. Under both conditions these oligosaccharides
      were predominantly in the characteristic cytosolic form, which terminates in a
      single N-acetylglucosamine (OS-GlcNAc(1)); this was also the case in the presence
      of DTT, which retains the G protein completely in the ER. However when cells
      infected with the VSV mutant were examined at 15 degrees C or exposed to CST,
      both of which represent conditions that impair ER-to-cytosol transport, the
      released oligosaccharides were almost exclusively (> 95%) in the vesicular OS
      GlcNAc(2) form; glucosidase blockade had a similar effect on the wild-type virus.
      Addition of puromycin to glucosidase-inhibited cells resulted in a pronounced
      reduction (> 90%) in oligosaccharide release, which reflected a comparable
      impairment in glycoprotein biosynthesis and indicated that the OS-GlcNAc(2)
      components originated from protein degradation rather than hydrolysis of
      oligosaccharide lipids. Our findings are consistent with N-deglycosylation of the
      VSV G protein in the ER and the subsequent transport of the released
      oligosaccharides to the cytosol where OS-GlcNAc(2) to OS-GlcNAc(1) conversion by
      an endo-beta-N-acetylglucosaminidase takes place. Studies with the ts045 G
      protein at the nonpermissive temperature permitted us to determine that it can be
      processed by Golgi endomannosidase although remaining endo H sensitive,
      supporting the concept that it recycles between the ER and cis-Golgi
      compartments.

PMID- 11588157
TI  - Galactosylation of N-linked oligosaccharides by human beta-1,4
      galactosyltransferases I, II, III, IV, V, and VI expressed in Sf-9 cells.
AB  - Several studies showed that Sf-9 cells can synthesize the galactosylated N-linked
      oligosaccharides if beta-1,4-galactosyltransferase (beta-1,4-GalT) is supplied.
      The full-length human beta-1,4-GalT I, II, III, IV, V, and VI cDNAs were
      independently transfected into Sf-9 cells, and the galactosylation of endogenous
      membrane glycoproteins was examined by lectin blot analysis using Ricinus
      communis agglutinin-I (RCA-I), which preferentially interacts with
      oligosaccharides terminated with Galbeta1-->4GlcNAc group. Several RCA-I-reactive
      bands appeared in all of the gene-transfected cells, and disappeared on treatment
      of blots with beta-1,4-galactosidase or N-glycanase prior to incubation with
      lectin. Introduction of the antisense beta-1,4-GalT II and V cDNAs separately
      into human colorectal adenocarcinoma SW480 cells, in which beta-1,4-GalT I, II,
      and V genes were expressed, resulted in the reduction of RCA-I binding toward N
      linked oligosaccharides of the membrane glycoproteins. Differences were found in
      their K(m) values toward UDP-Gal and GlcNAcbeta-S-pNP and in their acceptor
      specificities toward oligosaccharides with the GlcNAcbeta1-->4(GlcNAcbeta1-
      >2)Man branch and with the GlcNAcbeta1-->6(GlcNAcbeta1-->2)Man branch. These
      results indicate that beta-1,4-GalTs II, III, IV, V, and VI are involved in the N
      linked oligosaccharide biosynthesis cooperatively but not in a redundant manner
      with beta-1,4-GalT I within cells.

PMID- 11588158
TI  - N-acetylgalactosamine incorporation into a peptide containing consecutive
      threonine residues by UDP-N-acetyl-D-galactosaminide:polypeptide N
      acetylgalactosaminyltransferases.
AB  - A limited number of glycosylation products were generated in a cell-free system
      from a portion of the MUC2 tandem repeat, PTTTPITTTTK, when microsome fractions
      of human colon carcinoma LS174T cells were used as the source of UDP-N-acetyl-D
      galactosaminide:polypeptide N-acetylgalactosaminyltransferases (pp-GalNAc-T) in
      our previous work. The structures of all products suggested that there were only
      two biosynthetic pathways in the GalNAc incorporation into this peptide. In the
      present report, the putative biosynthetic intermediates, PTTT*PITTTTK (asterisk
      designates a GalNAc residue), PT*TTPITTTTK, PTT*T*PITT*T*TK, and PT*TTPIT*T*T*TK,
      of these two hypothetical pathways were used as acceptors to prove that these two
      pathways do exist. The incubation products of these glycopeptides, microsome
      fractions of LS174T cells, and UDP-GalNAc were fractionated by reverse-phase HPLC
      and their structures were determined using MALDI-TOF MS and peptide sequencing.
      The products from PTTT*PITTTTK were PTTT*PITTT*TK, PTTT*PITT*T*TK, PTT*T*PI
      TT*T*TK, PTT*T*PIT*T*T*TK, PT*T*T*PIT*T*T*TK, and PT*T*T*PIT*T*T*T*K. The
      products from PTT*-T*PITT*T*TK exactly corresponded to the products with five to
      seven GalNAc residues from PTTT*PITTTTK. The products from PT*TTPITTTTK were
      PT*TTPITT*TTK, PT*TTPIT*T*TTK, and PT*TTPIT*T*T*TK. PT*TTP-IT*T*T*TK was not
      converted further under the applied condition. All the products detected and
      analyzed were the same as those obtained when the unsubstituted peptide and
      microsome fractions of LS174T cells were incubated. Immunocytochemical analysis
      indicated that LS174T cells contain at least four pp-GalNAc-Ts (-T1, -T2, -T3,
      and -T4), suggesting that control of the order and the maximum number of GalNAc
      incorporation into this peptide is regulated through the coordinated actions of
      these and possibly other pp-GalNAc-Ts.

PMID- 11588159
TI  - The major gangliosides of human peripheral blood monocytes/macrophages: absence
      of ganglio series structures.
AB  - Sialoglycosphingolipids (gangliosides) are membrane components of eukaryotic
      cells that modulate cell signal transduction events. Discrepancies exist in the
      published descriptions of the gangliosides present in the human peripheral
      monocyte/macrophage. Macrophages were isolated from healthy human volunteers by
      two different methods. Their ganglioside fractions were isolated and examined by
      2D thin-layer mobility, enzymatic susceptibility, and mass spectral-collision
      induced dissociation-mass spectral analyses. Thin-layer ganglioside
      chromatographic patterns displayed four major doublets and were similar for
      monocytes/macrophages isolated by either apheresis/elutriation or density
      gradient centrifugation. All gangliosides were resistant to beta-galactosidase
      but sensitive to Clostridium perfringens sialidase, indicating the absence of
      terminal galactose residues and sialidase-resistant sialic acid moieties. Mass
      spectra indicated only three major sets of glycolipid components with mass
      heterogeneity in the ceramide portion of each set. In all the gangliosides, the
      ceramide moiety contained only C18 sphingosine with the heterogeneity produced by
      the presence of C16 or C24 fatty acid. One doublet was resistant to Newcastle
      disease virus sialidase, indicating the presence of an alpha(2-6)-linked sialic
      acid residue with the same mass as another doublet. All data was consistent with
      the following structures as the major gangliosides of human peripheral
      monocyte/macrophages: II(3)NeuAcLacCer (sialolactosyl ceramide, GM3), IV(3)- and
      IV(6)NeuAcnLcOse(4)Cer (sialoparagloboside, nLM1), and IV(3)NeuAcnLcOse(6)Cer (a
      sialohexosylceramide).

PMID- 11588160
TI  - Region-specific developmental specialization of GABA-glycine cosynapses in
      laminas I-II of the rat spinal dorsal horn.
AB  - The spinal dorsal horn is the first level of the CNS in which nociceptive input
      from sensory afferents is integrated and transmitted. Although inhibitory control
      in this region has a crucial impact on pain transmission, the respective
      contribution of GABA and glycine to this inhibition remains elusive. We have
      previously documented co-release of GABA and glycine at the same inhibitory
      synapse in spinal laminas I-II of adult rats [older than postnatal day 30 (P30)].
      However, despite this co-release, individual miniature inhibitory postsynaptic
      currents (mIPSCs) were mediated by either glycine receptors (GlyR) or GABA(A)
      receptors (GABA(A)R), yet never by the two together. In contrast, recent studies
      of ventral horn immature inhibitory synapses (</=P21) reported individual mIPSCs
      that were mediated by both GABA(A)Rs and GlyRs. This raises the question of
      whether mixed mIPSCs are present in immature lamina I-II neurons yet are lost
      through a maturation-dependent synaptic specialization. To test this, we recorded
      mIPSCs using patch-clamp techniques in lamina I-II neurons in spinal slices taken
      at different stages of development. We found that, in neurons younger than P23,
      both GlyR-only and GABA(A)R-only mIPSCs could be recorded, in addition to mixed
      GABA(A)R-GlyR mIPSCs. With maturation however, both lamina I-II neurons gradually
      discontinued exhibiting mixed mIPSCs, although with differing patterns of
      specialization. Yet, at all developmental stages, benzodiazepine administration
      could unmask mixed mIPSCs. Together, these findings indicate that, although GABA
      and glycine are continually co-released throughout development, junctional
      codetection ceases by adulthood. This indicates an age-dependent postsynaptic
      tuning of inhibitory synapses that occurs in a region-specific manner.

PMID- 11588161
TI  - Therapeutic efficacy in experimental polyarthritis of viral-driven enkephalin
      overproduction in sensory neurons.
AB  - Rheumatoid arthritis is characterized by erosive inflammation of the joints, new
      bone proliferation, and ankylosis, leading to severely reduced locomotion and
      intense chronic pain. In a model of this disease, adjuvant-induced polyarthritis
      in the rat, neurons involved in pain transmission and control undergo plastic
      changes, especially at the spinal level. These changes affect notably neurons
      that contain opioids, such as enkephalins deriving from preproenkephalin A (PA)
      precursor protein. Using recombinant herpes simplex virus containing rat PA cDNA,
      we enhanced enkephalin synthesis in sensory neurons of polyarthritic rats. This
      treatment markedly improved locomotion and reduced hyperalgesia. Furthermore, the
      progression of bone destruction slowed down, which is the most difficult target
      to reach in the treatment of patients suffering from arthritis. These data
      demonstrate the therapeutic efficacy of enkephalin overproduction in a model of
      systemic inflammatory and painful chronic disorder.

PMID- 11588162
TI  - Estimation of quantal size and number of functional active zones at the calyx of
      Held synapse by nonstationary EPSC variance analysis.
AB  - At the large excitatory calyx of Held synapse, the quantal size during an evoked
      EPSC and the number of active zones contributing to transmission are not known.
      We developed a nonstationary variant of EPSC fluctuation analysis to determine
      these quantal parameters. AMPA receptor-mediated EPSCs were recorded in slices of
      young (postnatal 8-10 d) rats after afferent fiber stimulation, delivered in
      trains to induce synaptic depression. The means and the variances of EPSC
      amplitudes were calculated across trains for each stimulus number. During 10 Hz
      trains at 2 mm Ca(2+) concentration ([Ca(2+)]), we found linear EPSC variance
      mean relationships, with a slope that was in good agreement with the quantal size
      obtained from amplitude distributions of spontaneous miniature EPSCs. At high
      release probability with 10 or 15 mm [Ca(2+)], competitive antagonists were used
      to partially block EPSCs. Under these conditions, the EPSC variance-mean plots
      could be fitted with parabolas, giving estimates of quantal size and of the
      binomial parameter N. With the rapidly dissociating antagonist kynurenic acid,
      quantal sizes were larger than with a slowly dissociating antagonist, suggesting
      that the effective glutamate concentration was increased at high release
      probability. Considering the possibility of multivesicular release and moderate
      saturation of postsynaptic AMPA receptors, we conclude that the binomial
      parameter N (637 +/- 117; mean +/- SEM) represents an upper limit estimate of the
      number of functional active zones. We estimate that during normal synaptic
      transmission, the probability of vesicle fusion at single active zones is in the
      range of 0.25-0.4.

PMID- 11588163
TI  - Freshly isolated hippocampal CA1 astrocytes comprise two populations differing in
      glutamate transporter and AMPA receptor expression.
AB  - We have shown previously that process-bearing GFAP+ astrocytes freshly isolated
      from rat hippocampus CA1 and CA3 regions are heterogeneous in ion channel
      expression and K(+) uptake capabilities, such that two distinct populations of
      astrocytes can be described (Zhou and Kimelberg, 2000). In the present study, we
      report that glutamate transporter (GT) currents can only be measured from one
      type of these freshly isolated hippocampal CA1 astrocytes [variably rectifying
      astrocytes (VRAs)] but were not detectable in the second type of astrocyte
      [outwardly rectifying astrocytes (ORAs)]. The GT currents showed a strict Na(+)
      dependency and high affinity for glutamate (EC(50) of 4 +/- 1.1 microm). The
      astrocytes lacking GT currents (ORAs) showed an AMPA receptor current density (55
      pA/pF) that was 42-fold higher than VRAs (1.3 pA/pF). In contrast, the GABA(A)
      currents were of comparable current density in both types. The specificity of
      these differences makes it unlikely that they are attributable to preparative
      damage. Therefore, these findings strongly indicate that, within a single region
      of the hippocampus, GFAP+ astrocytes comprise a functionally diverse population
      that are qualitatively different in their functional glutamate transporter and
      quantitatively different in their functional AMPA receptor expression. This
      heterogeneity implies that GFAP+ astrocytes may participate in or modulate
      glutamate synaptic transmission differently.

PMID- 11588164
TI  - Gating properties of Na(v)1.7 and Na(v)1.8 peripheral nerve sodium channels.
AB  - Several distinct components of voltage-gated sodium current have been recorded
      from native dorsal root ganglion (DRG) neurons that display differences in gating
      and pharmacology. This study compares the electrophysiological properties of two
      peripheral nerve sodium channels that are expressed selectively in DRG neurons
      (Na(v)1.7 and Na(v)1.8). Recombinant Na(v)1.7 and Na(v)1.8 sodium channels were
      coexpressed with the auxiliary beta(1) subunit in Xenopus oocytes. In this system
      coexpression of the beta(1) subunit with Na(v)1.7 and Na(v)1.8 channels results
      in more rapid inactivation, a shift in midpoints of steady-state activation and
      inactivation to more hyperpolarizing potentials, and an acceleration of recovery
      from inactivation. The coinjection of beta(1) subunit also significantly
      increases the expression of Na(v)1.8 by sixfold but has no effect on the
      expression of Na(v)1.7. In addition, a great percentage of Na(v)1.8+beta(1)
      channels is observed to enter rapidly into the slow inactivated states, in
      contrast to Nav1.7+beta(1) channels. Consequently, the rapid entry into slow
      inactivation is believed to cause a frequency-dependent reduction of
      Na(v)1.8+beta(1) channel amplitudes, seen during repetitive pulsing between 1 and
      2 Hz. However, at higher frequencies (>20 Hz) Na(v)1.8+beta(1) channels reach a
      steady state to approximately 42% of total current. The presence of this steady
      state sodium channel activity, coupled with the high activation threshold (V(0.5)
      = -3.3 mV) of Na(v)1.8+beta(1), could enable the nociceptive fibers to fire
      spontaneously after nerve injury.

PMID- 11588165
TI  - Characterization of the functional heterologous desensitization of hypothalamic 5
      HT(1A) receptors after 5-HT(2A) receptor activation.
AB  - Desensitization of 5-HT(1A) receptors could be involved in the long-term
      therapeutic effect of anxiolytic and antidepressant drugs. Pretreatment of rats
      with the 5-HT(2A/2C) agonist DOI induces an attenuation of hypothalamic 5-HT(1A)
      receptor-G(z)-protein signaling, measured as the ACTH and oxytocin responses to
      an injection of the 5-HT(1A) agonist 8-OH-DPAT. We characterized this functional
      heterologous desensitization of 5-HT(1A) receptors in rats and examined some of
      the mechanisms that are involved. A time course experiment revealed that DOI
      produces a delayed and reversible reduction of the ACTH and oxytocin responses to
      an 8-OH-DPAT challenge. The maximal desensitization occurred at 2 hr, and it
      disappeared 24 hr after DOI injection. The desensitization was dose-dependent,
      and it shifted the oxytocin and ACTH dose-response curves of 8-OH-DPAT to the
      right (increased ED(50)) with no change in their maximal responses (E(max)). The
      5-HT(2A) receptor antagonist MDL 100,907 prevented the DOI-induced
      desensitization, indicating that 5-HT(2A) receptors mediate the effect of DOI.
      Analysis of the components of the 5-HT(1A) receptor-G(z)-protein signaling system
      showed that DOI did not alter the level of membrane-associated G(z)-proteins in
      the hypothalamus. Additionally, DOI did not alter the binding of [(3)H]8-OH-DPAT
      or the inhibition by GTPgammaS of [(3)H]8-OH-DPAT binding in the hypothalamus. In
      conclusion, the activation of 5-HT(2A) receptors induces a transient functional
      desensitization of 5-HT(1A) receptor signaling in the hypothalamus, which may
      occur distal to the 5-HT(1A) receptor-G(z)-protein interface.

PMID- 11588166
TI  - Protein kinase c increases the apparent affinity of the release machinery to Ca2+
      by enhancing the release machinery downstream of the Ca2+ sensor.
AB  - Modulation of the release probability of releasable vesicles in response to
      Ca(2+) influx (Prob(Ca)) is involved in mediating several forms of synaptic
      plasticity, including short-term depression, short-term augmentation, and
      potentiation induced by protein kinases. Given such an important role, however,
      the mechanism underlying modulation of the Prob(Ca) is unclear. We addressed this
      question by investigating how the activation of protein kinase C modulates the
      Prob(Ca) at a calyx-type nerve terminal in rat brainstem. Various lengths of step
      depolarization were applied to the nerve terminal to evoke different amounts of
      Ca(2+) currents and capacitance jumps, the latter of which reflect vesicle
      release. The relationship between the capacitance jump and the Ca(2+) current
      integral was sigmoidal and was fit well with a Hill function. The sigmoidal
      relationship was shifted significantly to the left during the application of the
      PKC activator 12-myristate 13-acetate (PMA), suggesting that PMA increases the
      apparent affinity of the release machinery to Ca(2+). This effect was blocked in
      large part by the application of the PKC inhibitor bisindolylmaleimide,
      suggesting that the effect is mediated mainly by the activation of PKC. We also
      found that PMA increased the rate of miniature EPSCs evoked by the application of
      hypertonic sucrose solution, which triggers release downstream of the Ca(2+)
      influx. Taken together, our results suggest that PKC enhances the apparent
      affinity of the release machinery to Ca(2+) by a mechanism downstream of the
      binding between Ca(2+) and its sensor. These results have provided the first
      example of the mechanisms underlying modulation of the Prob(Ca).

PMID- 11588167
TI  - Oscillating on borrowed time: diffusible signals from immortalized
      suprachiasmatic nucleus cells regulate circadian rhythmicity in cultured
      fibroblasts.
AB  - The capacity to generate circadian rhythms endogenously and to confer this
      rhythmicity to other cells was compared in immortalized cells derived from the
      suprachiasmatic nucleus (SCN) and a fibroblast line to differentiate SCN
      pacemaker properties from the oscillatory behavior of non-clock tissues. Only
      SCN2.2 cells were capable of endogenously generating circadian rhythms in 2
      deoxyglucose uptake and Per gene expression. Similar to SCN function in vivo,
      SCN2.2 cells imposed rhythms of metabolic activity and Per gene expression on
      cocultured NIH/3T3 fibroblasts via a diffusible signal. The conferred rhythms in
      NIH/3T3 cells were phase delayed by 4-12 hr relative to SCN2.2 circadian
      patterns, thus resembling the phase relationship between SCN and peripheral
      tissue rhythms in vivo. Sustained metabolic rhythmicity in NIH/3T3 cells was
      dependent on continued exposure to SCN2.2-specific outputs. In response to a
      serum shock the NIH/3T3 fibroblasts exhibited recurrent oscillations in clock
      gene expression, but not in metabolic activity. These molecular rhythms in serum
      shocked fibroblasts cycled in a phase relationship similar to that observed in
      the SCN in vivo; peak Per1 and Per2 mRNA expression preceded the rhythmic maxima
      in Cry1 and Cry2 mRNA levels by 4 hr. Despite these clock gene oscillations the
      serum-shocked NIH/3T3 cells failed to drive circadian rhythms of Per1 and Per2
      expression in cocultures of untreated fibroblasts, suggesting that expression and
      circadian regulation of the Per and Cry genes are not sufficient to confer
      pacemaker function. Therefore, SCN-specific outputs are necessary to drive
      circadian rhythms of metabolic activity, and these output signals are not a
      direct product of clock gene oscillations.

PMID- 11588168
TI  - Opposing changes in phosphorylation of specific sites in synapsin I during Ca2+
      dependent glutamate release in isolated nerve terminals.
AB  - Synapsins are major neuronal phosphoproteins involved in regulation of
      neurotransmitter release. Synapsins are well established targets for multiple
      protein kinases within the nerve terminal, yet little is known about
      dephosphorylation processes involved in regulation of synapsin function. Here, we
      observed a reciprocal relationship in the phosphorylation-dephosphorylation of
      the established phosphorylation sites on synapsin I. We demonstrate that, in
      vitro, phosphorylation sites 1, 2, and 3 of synapsin I (P-site 1 phosphorylated
      by cAMP-dependent protein kinase; P-sites 2 and 3 phosphorylated by Ca(2+)
      calmodulin-dependent protein kinase II) were excellent substrates for protein
      phosphatase 2A, whereas P-sites 4, 5, and 6 (phosphorylated by mitogen-activated
      protein kinase) were efficiently dephosphorylated only by Ca(2+)-calmodulin
      dependent protein phosphatase 2B-calcineurin. In isolated nerve terminals, rapid
      changes in synapsin I phosphorylation were observed after Ca(2+) entry, namely, a
      Ca(2+)-dependent phosphorylation of P-sites 1, 2, and 3 and a Ca(2+)-dependent
      dephosphorylation of P-sites 4, 5, and 6. Inhibition of calcineurin activity by
      cyclosporin A resulted in a complete block of Ca(2+)-dependent dephosphorylation
      of P-sites 4, 5, and 6 and correlated with a prominent increase in ionomycin
      evoked glutamate release. These two opposing, rapid, Ca(2+)-dependent processes
      may play a crucial role in the modulation of synaptic vesicle trafficking within
      the presynaptic terminal.

PMID- 11588169
TI  - Myr 8, a novel unconventional myosin expressed during brain development
      associates with the protein phosphatase catalytic subunits 1alpha and 1gamma1.
AB  - Directed neuronal, astroglial, and oligodendroglial cell migrations comprise a
      prominent feature of mammalian brain development. Because molecular motor
      proteins have been implicated in a wide spectrum of processes associated with
      cell motility, we initiated studies to define the pool of myosins in migrating
      cerebellar granule neurons and type-1 neocortical astrocytes. Our analyses
      identified two isoforms of a novel unconventional myosin, which we have cloned,
      sequenced, and designated myr 8a and 8b (eighth unconventional myosin from rat).
      Phylogenetic analysis indicates that myr 8 myosins comprise a new class of
      myosins, which we have designated class XVI. The head domain contains a large N
      terminal extension composed of multiple ankyrin repeats, which are implicated in
      mediating an association with the protein phosphatase 1 (PP1) catalytic subunits
      1alpha and 1gamma. The motor domain is followed by a single putative light-chain
      binding domain. The tail domain of myr 8a is comparatively short with a net
      positive charge, whereas the tail domain of myr 8b is extended, bears an overall
      neutral charge, and reveals several stretches of poly-proline residues. Neither
      the myr 8a nor the myr 8b sequence reveals alpha-helical coiled-coil motifs,
      suggesting that these myosins exist as monomers. Both immunoblot and Northern
      blot analyses indicate that myr 8b is the predominant isoform expressed in brain,
      principally at developmental time periods. The structural features and restricted
      expression patterns suggest that members of this novel class of unconventional
      myosins comprise a mechanism to target selectively the protein phosphatase 1
      catalytic subunits 1alpha and/or 1gamma in developing brain.

PMID- 11588170
TI  - An evaluation of synapse independence.
AB  - If, as is widely believed, information is stored in the brain as distributed
      modifications of synaptic efficacy, it can be argued that the storage capacity of
      the brain will be maximized if the number of synapses that operate independently
      is as large as possible. The majority of synapses in the brain are glutamatergic;
      their independence will be compromised if glutamate released at one synapse can
      significantly activate receptors at neighboring synapses. There is currently no
      agreement on whether "spillover" after the liberation of a vesicle will
      significantly activate receptors at neighboring synapses. To evaluate the
      independence of central synapses, it is necessary to compare synaptic responses
      with those generated at neighboring synapses by glutamate spillover. Here,
      synaptic activation and spillover responses are simulated in a model, based on
      data for hippocampal synapses, that includes an approximate representation of the
      extrasynaptic space. Recently-published data on glutamate transporter
      distribution and properties are incorporated. Factors likely to influence
      synaptic or spillover responses are investigated. For release of one vesicle, it
      is estimated that the mean response at the nearest neighboring synapse will be
      <5% of the synaptic response. It is concluded that synapses can operate
      independently.

PMID- 11588171
TI  - An NMDA receptor signaling complex with protein phosphatase 2A.
AB  - Regulation of protein phosphatase 2A (PP2A) activity and NMDA receptor (NMDAR)
      phosphorylation state contribute to the modulation of synaptic plasticity, yet
      these two mechanisms have not been functionally linked. The NMDAR subunit NR3A is
      equipped with a unique carboxyl domain that is different from other NMDAR
      subunits. We hypothesized that the NR3A C-terminal intracellular domain might
      serve as synaptic anchor for the phosphatase in the developing CNS. A cDNA
      library was screened by the yeast two-hybrid method using the NR3A carboxyl
      domain as the bait. The catalytic subunit of the serine-threonine PP2A was found
      to be associated with the NR3A carboxyl domain. Immunoprecipitation studies
      indicated that the NR3A subunit formed a stable complex with PP2A in the rat
      brain in vivo. Association of PP2A with NMDARs led to an increase in the
      phosphatase activity of PP2A and the dephosphorylation of serine 897 of the NMDAR
      subunit NR1. Stimulation of NMDARs led to the dissociation of PP2A from the
      complex and the reduction of PP2A activity. A peptide corresponding to the PP2A
      NR3A binding domain functioned as a negative regulator of PP2A activity. These
      data suggest that NMDARs are allosteric modulators of PP2A, which in turn
      controls their phosphorylation state. The data delineate a mechanistic model of
      the dynamic regulation of a PP2A-NMDAR signaling complex, mediated by the
      interaction of NR3A and PP2A, and suggest a novel NMDAR-mediated signaling
      mechanism in addition to the traditional ionotropic functions of NMDARs.

PMID- 11588172
TI  - Ultrastructural distribution of the alpha7 nicotinic acetylcholine receptor
      subunit in rat hippocampus.
AB  - Acetylcholine (ACh) is an important neurotransmitter in the mammalian brain; it
      is implicated in arousal, learning, and other cognitive functions. Recent studies
      indicate that nicotinic receptors contribute to these cholinergic effects, in
      addition to the established role of muscarinic receptors. In the hippocampus,
      where cholinergic involvement in learning and memory is particularly well
      documented, alpha7 nicotinic acetylcholine receptor subunits (alpha7 nAChRs) are
      highly expressed, but their precise ultrastructural localization has not been
      determined. Here, we describe the results of immunogold labeling of serial
      ultrathin sections through stratum radiatum of area CA1 in the rat. Using both
      anti-alpha7 nAChR immunolabeling and alpha-bungarotoxin binding, we find that
      alpha7 nAChRs are present at nearly all synapses in CA1 stratum radiatum, with
      immunolabeling present at both presynaptic and postsynaptic elements.
      Morphological considerations and double immunolabeling indicate that GABAergic as
      well as glutamatergic synapses bear alpha7 nAChRs, at densities approaching those
      observed for glutamate receptors in CA1 stratum radiatum. Postsynaptically,
      alpha7 nAChRs often are distributed at dendritic spines in a perisynaptic
      annulus. In the postsynaptic cytoplasm, immunolabeling is associated with spine
      apparatus and other membranous structures, suggesting that alpha7 nAChRs may
      undergo dynamic regulation, with insertion into the synapse and subsequent
      internalization. The widespread and substantial expression of alpha7 nAChRs at
      synapses in the hippocampus is consistent with an important role in mediating
      and/or modulating synaptic transmission, plasticity, and neurodegeneration.

PMID- 11588173
TI  - Molecular heterogeneity of the voltage-gated fast transient outward K+ current,
      I(Af), in mammalian neurons.
AB  - Recently, we identified four kinetically distinct voltage-gated K(+) currents,
      I(Af), I(As), I(K), and I(SS), in rat superior cervical ganglion (SCG) neurons
      and demonstrated that I(Af) and I(As) are differentially expressed in type I
      (I(Af), I(K), I(SS)), type II (I(Af), I(As), I(K), I(SS)), and type III (I(K),
      I(SS)) SCG cells. In addition, we reported that I(Af) is eliminated in most (
      approximately 70%) SCG cells expressing Kv4.2W362F, a Kv4 subfamily-specific
      dominant negative. The molecular correlate(s) of the residual I(Af), as well as
      that of I(As), I(K), and I(SS), however, are unknown. The experiments here were
      undertaken to explore the role of Kv1 alpha-subunits in the generation of voltage
      gated K(+) currents in SCG neurons. Using the Biolistics Gene Gun, cDNA
      constructs encoding a Kv1 subfamily-specific dominant negative, Kv1.5W461F, and
      enhanced green fluorescent protein (EGFP) were introduced into SCG neurons. Whole
      cell recordings from EGFP-positive Kv1.5W461F-expressing cells revealed a
      selective decrease in the percentage of type I cells and an increase in type III
      cells, indicating that I(Af) is gated by Kv1 alpha-subunits in a subset of type I
      SCG neurons. I(Af) is eliminated in all SCG cells expressing both Kv1.5W461F and
      Kv4.2W362F. I(Af) tau(decay) values in Kv1.5W461F-expressing and Kv4.2W362F
      expressing type I cells are significantly different, revealing that Kv1 and Kv4
      alpha-subunits encode kinetically distinct I(Af) channels. Expression of
      Kv1.5W461F increases excitability by decreasing action potential current
      thresholds and converts phasic cells to adapting or tonic firing. Interestingly,
      the molecular heterogeneity of I(Af) channels has functional significance because
      Kv1- and Kv4-encoded I(Af) play distinct roles in the regulation of neuronal
      excitability.

PMID- 11588174
TI  - Induction of mossy fiber --> Ca3 long-term potentiation requires translocation of
      synaptically released Zn2+.
AB  - The mammalian CNS contains an abundance of chelatable Zn(2+) sequestered in the
      vesicles of glutamatergic terminals. These vesicles are particularly numerous in
      hippocampal mossy fiber synapses of the hilar and CA3 regions. Our recent
      observation of frequency-dependent Zn(2+) release from mossy fiber synaptic
      terminals and subsequent entry into postsynaptic neurons has prompted us to
      investigate the role of synaptically released Zn(2+) in the induction of long
      term potentiation (LTP) in field CA3 of the hippocampus. The rapid removal of
      synaptically released Zn(2+) with the membrane-impermeable Zn(2+) chelator CaEDTA
      (10 mm) blocked induction of NMDA receptor-independent mossy fiber LTP by high
      frequency electrical stimulation (HFS) in rat hippocampal slices. Mimicking
      Zn(2+) release by bath application of Zn(2+) (50-100 microm) without HFS induced
      a long-lasting potentiation of synaptic transmission that lasted more than 3 hr.
      Moreover, our experiments indicate the effects of Zn(2+) were not attributable to
      its interaction with extracellular membrane proteins but required its entry into
      presynaptic or postsynaptic neurons. Co-released glutamate is also essential for
      induction of LTP under physiological conditions, in part because it allows Zn(2+)
      entry into postsynaptic neurons. These results indicate that synaptically
      released Zn(2+), acting as a second messenger, is necessary for the induction of
      LTP at mossy fiber-->CA3 synapses of hippocampus.

PMID- 11588175
TI  - Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation
      induced expression of acid-sensing ion channels in nociceptors.
AB  - Nonsteroid anti-inflammatory drugs (NSAIDs) are major drugs against inflammation
      and pain. They are well known inhibitors of cyclooxygenases (COXs). However, many
      studies indicate that they may also act on other targets. Acidosis is observed in
      inflammatory conditions such as chronic joint inflammation, in tumors and after
      ischemia, and greatly contributes to pain and hyperalgesia. Administration of
      NSAIDs reduces low-pH-induced pain. The acid sensitivity of nociceptors is
      associated with activation of H(+)-gated ion channels. Several of these, cloned
      recently, correspond to the acid-sensing ion channels (ASICs) and others to the
      vanilloid receptor family. This paper shows (1) that ASIC mRNAs are present in
      many small sensory neurons along with substance P and isolectin B4 and that, in
      case of inflammation, ASIC1a appears in some larger Abeta fibers, (2) that NSAIDs
      prevent the large increase of ASIC expression in sensory neurons induced by
      inflammation, and (3) that NSAIDs such as aspirin, diclofenac, and flurbiprofen
      directly inhibit ASIC currents on sensory neurons and when cloned ASICs are
      heterologously expressed. These results suggest that the combined capacity to
      block COXs and inhibit both inflammation-induced expression and activity of ASICs
      present in nociceptors is an important factor in the action of NSAIDs against
      pain.

PMID- 11588176
TI  - The neuronal form of adaptor protein-3 is required for synaptic vesicle formation
      from endosomes.
AB  - Heterotetrameric adaptor complexes vesiculate donor membranes. One of the adaptor
      protein complexes, AP-3, is present in two forms; one form is expressed in all
      tissues of the body, whereas the other is restricted to brain. Mice lacking both
      the ubiquitous and neuronal forms of AP-3 exhibit neurological disorders that are
      not observed in mice that are mutant only in the ubiquitous form. To begin to
      understand the role of neuronal AP-3 in neurological disease, we investigated its
      function in in vitro assays as well as its localization in neural tissue. In the
      presence of GTPgammaS both ubiquitous and neuronal forms of AP-3 can bind to
      purified synaptic vesicles. However, only the neuronal form of AP-3 can produce
      synaptic vesicles from endosomes in vitro. We also identified that the expression
      of neuronal AP-3 is limited to varicosities of neuronal-like processes and is
      expressed in most axons of the brain. Although the AP-2/clathrin pathway is the
      major route of vesicle production and the relatively minor neuronal AP-3 pathway
      is not necessary for viability, the absence of the latter could lead to the
      neurological abnormalities seen in mice lacking the expression of AP-3 in brain.
      In this study we have identified the first brain-specific function for a neuronal
      adaptor complex.

PMID- 11588177
TI  - GABA(B2) is essential for g-protein coupling of the GABA(B) receptor heterodimer.
AB  - GABA(B) receptors are unique among G-protein-coupled receptors (GPCRs) in their
      requirement for heterodimerization between two homologous subunits, GABA(B1) and
      GABA(B2), for functional expression. Whereas GABA(B1) is capable of binding
      receptor agonists and antagonists, the role of each GABA(B) subunit in receptor
      signaling is unknown. Here we identified amino acid residues within the second
      intracellular domain of GABA(B2) that are critical for the coupling of GABA(B)
      receptor heterodimers to their downstream effector systems. Our results provide
      strong evidence for a functional role of the GABA(B2) subunit in G-protein
      coupling of the GABA(B) receptor heterodimer. In addition, they provide evidence
      for a novel "sequential" GPCR signaling mechanism in which ligand binding to one
      heterodimer subunit can induce signal transduction through the second partner of
      a heteromeric complex.

PMID- 11588178
TI  - Induction of alpha-synuclein aggregation by intracellular nitrative insult.
AB  - Brain lesions containing filamentous and aggregated alpha-synuclein are hallmarks
      of neurodegenerative synucleinopathies. Oxidative stress has been implicated in
      the formation of these lesions. Using HEK 293 cells stably transfected with wild
      type and mutant alpha-synuclein, we demonstrated that intracellular generation of
      nitrating agents results in the formation of alpha-synuclein aggregates. Cells
      were exposed simultaneously to nitric oxide- and superoxide-generating compounds,
      and the intracellular formation of peroxynitrite was demonstrated by monitoring
      the oxidation of dihydrorhodamine 123 and the nitration of alpha-synuclein. Light
      microscopy using antibodies against alpha-synuclein and electron microscopy
      revealed the presence of perinuclear aggregates under conditions in which
      peroxynitrite was generated but not when cells were exposed to nitric oxide- or
      superoxide-generating compounds separately. alpha-Synuclein aggregates were
      observed in 20-30% of cells expressing wild-type or A53T mutant alpha-synuclein
      and in 5% of cells expressing A30P mutant alpha-synuclein. No evidence of
      synuclein aggregation was observed in untransfected cells or cells expressing
      beta-synuclein. In contrast, selective inhibition of the proteasome resulted in
      the formation of aggregates detected with antibodies to ubiquitin in the majority
      of the untransfected cells and cells expressing alpha-synuclein. However, alpha
      synuclein did not colocalize with these aggregates, indicating that inhibition of
      the proteasome does not promote alpha-synuclein aggregation. In addition,
      proteasome inhibition did not alter the steady-state levels of alpha-synuclein,
      but addition of the lysosomotropic agent ammonium chloride significantly
      increased the amount of alpha-synuclein, indicating that lysosomes are involved
      in degradation of alpha-synuclein. Our data indicate that nitrative and oxidative
      insult may initiate pathogenesis of alpha-synuclein aggregates.

PMID- 11588179
TI  - AMPA receptor channels with long-lasting desensitization in bipolar interneurons
      contribute to synaptic depression in a novel feedback circuit in layer 2/3 of rat
      neocortex.
AB  - A novel, local inhibitory circuit in layer 2/3 of rat somatosensory cortex is
      described that connects pyramidal cells reciprocally with GABAergic vasoactive
      intestinal polypeptide-immunoreactive bipolar interneurons. In paired whole-cell
      recordings, the glutamatergic unitary responses (EPSPs or EPSCs) in bipolar cells
      evoked by repetitive (10 Hz) stimulation of a pyramidal cell show strong
      frequency-dependent depression. Unitary IPSPs evoked in pyramidal cells by
      repetitive stimulation of bipolar cells, on average, maintained their amplitude.
      This suggests that the excitatory synapses on bipolar cells act as a low-pass
      filter in the reciprocal pyramid-to-bipolar circuit. The EPSCs in bipolar cells
      are mediated predominantly by AMPA receptor (AMPAR) channels. AMPARs desensitize
      rapidly and recover slowly from desensitization evoked by a brief pulse of
      glutamate. In slices, reduction of AMPAR desensitization by cyclothiazide (50-100
      microm) or conditioning steady-state desensitization induced by application of
      extracellular AMPA (50 nm) or glutamate (50 microm) strongly reduced synaptic
      depression. It is concluded that in the local circuits between pyramidal and
      bipolar cells the desensitization of AMPARs in bipolar cells contributes to low
      pass feedback inhibition of layer 2/3 pyramidal neurons by bipolar cells.

PMID- 11588180
TI  - Long-lasting aberrant tubulovesicular membrane inclusions accumulate in
      developing motoneurons after a sublethal excitotoxic insult: a possible model for
      neuronal pathology in neurodegenerative disease.
AB  - We have previously shown that chronic treatment of chick embryos [from embryonic
      day 5 (E5) to E9] with NMDA rescues spinal cord motoneurons (MNs) from programmed
      cell death. In this situation, MNs exhibit a reduced vulnerability to acute
      excitotoxic lesions and downregulate NMDA and AMPA-kainate receptors. Here, we
      report that this treatment results in long-lasting sublethal structural changes
      in MNs. In Nissl-stained sections from the spinal cord of NMDA-treated embryos,
      MNs display an area adjacent to an eccentrically positioned nucleus in which
      basophilia is excluded. Ultrastructurally, MNs accumulate tubulovesicular
      structures surrounded by Golgi stacks. Thiamine pyrophosphatase but not acid
      phosphatase was detected inside the tubulovesicular structures, which are
      resistant to disruption by brefeldin A or monensin. Immunocytochemistry reveals
      changes in the content and distribution of calcitonin gene-related peptide, the
      KDEL receptor, the early endosomal marker EEA1, and the recycling endosome marker
      Rab11, indicating that a dysfunction in membrane trafficking and protein sorting
      occurs in these MNs. FM1-43, a marker of the endocytic pathway, strongly
      accumulates in MNs from isolated spinal cords after chronic NMDA treatment.
      Changes in the distribution of cystatin C and presenilin-1 and an accumulation of
      amyloid precursor protein and beta-amyloid product were also observed in NMDA
      treated MNs. None of these alterations involve an interruption of MN-target
      (muscle) connections, as detected by the retrograde tracing of MNs with cholera
      toxin B subunit. These results demonstrate that chronic NMDA treatment induces
      severe changes in the motoneuronal endomembrane system that may be related to
      some neuropathological alterations described in human MN disease.

PMID- 11588181
TI  - Late-onset corticohippocampal neurodepletion attributable to catastrophic failure
      of oxidative phosphorylation in MILON mice.
AB  - We generated mitochondrial late-onset neurodegeneration (MILON) mice with
      postnatal disruption of oxidative phosphorylation in forebrain neurons. They
      develop normally and display no overt behavioral disturbances or histological
      changes during the first 5 months of life. The MILON mice display reduced levels
      of mitochondrial DNA and mitochondrial RNA from 2 and 4 months of age,
      respectively, and severely respiratory chain-deficient neurons from 4 months of
      age. Surprisingly, these respiratory chain-deficient neurons are viable for at
      least 1 month without showing signs of neurodegeneration or major induction of
      defenses against oxidative stress. Prolonged neuronal respiratory chain
      deficiency is thus required for the induction of neurodegeneration. Before
      developing neurological symptoms, MILON mice show increased vulnerability to
      excitotoxic stress. We observed a markedly enhanced sensitivity to excitotoxic
      challenge, manifest as an abundance of terminal deoxynucleotidyl transferase
      mediated biotinylated UTP nick end labeling (TUNEL) reactive cells after kainic
      acid injection, in 4-month-old MILON mice, showing that respiratory chain
      deficient neurons are more vulnerable to stress. At approximately 5-5.5 months of
      age, MILON mice start to show signs of disease, followed by death shortly
      thereafter. The debut of overt disease in MILON mice coincides with onset of
      rapidly progressive neurodegeneration and massive cell death in hippocampus and
      neocortex. This profound neurodegenerative process is manifested as axonal
      degeneration, gliosis, and abundant TUNEL-positive nuclei. The MILON mouse model
      provides a novel and powerful tool for additional studies of the role for
      respiratory chain deficiency in neurodegeneration and aging.

PMID- 11588182
TI  - Rna-binding protein Musashi2: developmentally regulated expression in neural
      precursor cells and subpopulations of neurons in mammalian CNS.
AB  - Musashi1 (Msi1) is a mammalian neural RNA-binding protein highly enriched in
      neural precursor cells that are capable of generating both neurons and glia
      during embryonic and postnatal CNS development. Here, we identified Musashi2
      (Msi2), a novel mammalian RNA-binding protein that exhibits high sequence
      similarity to Msi1. The Msi2 transcript appeared to be distributed ubiquitously
      in a wide variety of tissues, consistent with the mRNA distribution of its
      Xenopus homolog, xrp1. However, the present study revealed cell type-specific and
      developmentally regulated expression of Msi2 in the mammalian CNS. Interestingly,
      Msi2 was expressed prominently in precursor cells in the ventricular zone and
      subventricular zone with the same pattern as Msi1 throughout CNS development. In
      the postnatal and adult CNS, this concurrent expression of Msi2 and Msi1 was seen
      in cells of the astrocyte lineage, including ependymal cells, a possible source
      for postnatal CNS stem cells. During neurogenesis, the expression of both Msi2
      and Msi1 was lost in most postmitotic neurons, whereas Msi2 expression persisted
      in a subset of neuronal lineage cells, such as parvalbumin-containing GABA
      neurons in the neocortex and neurons in several nuclei of the basal ganglia. Msi2
      may have a unique role that is required for the generation and/or maintenance of
      specific neuronal lineages. Furthermore, in vitro studies showed that Msi2 and
      Msi1 have similar RNA-binding specificity. These two RNA-binding proteins may
      exert common functions in neural precursor cells by regulating gene expression at
      the post-transcriptional level.

PMID- 11588183
TI  - Neuroprotection through delivery of glial cell line-derived neurotrophic factor
      by neural stem cells in a mouse model of Parkinson's disease.
AB  - Neural stem cells (NSCs) have been proposed as tools for treating
      neurodegeneration because of their capacity to give rise to cell types
      appropriate to the structure in which they are grafted. In the present work, we
      explore the ability of NSCs to stably express transgenes and locally deliver
      soluble molecules with neuroprotective activity, such as glial cell line-derived
      neurotrophic factor (GDNF). NSCs engineered to release GDNF engrafted well in the
      host striatum, integrated and gave rise to neurons, astrocytes, and
      oligodendrocytes, and maintained stable high levels of GDNF expression for at
      least 4 months. The therapeutic potential of intrastriatal GDNF-NSCs grafts was
      tested in a mouse 6-hydroxydopamine model of Parkinson's disease. We found that
      GDNF-NSCs prevented the degeneration of dopaminergic neurons in the substantia
      nigra and reduced behavioral impairment in these animals. Thus, our results
      demonstrate that NSCs efficiently express therapeutic levels of GDNF in vivo,
      suggesting a use for NSCs engineered to release neuroprotective molecules in the
      treatment of neurodegenerative disorders, including Parkinson's disease.

PMID- 11588184
TI  - Deposition of the NG2 proteoglycan at nodes of Ranvier in the peripheral nervous
      system.
AB  - The node of Ranvier is a complex macromolecular assembly of ion channels and
      other proteins that is specialized for the rapid propagation of the action
      potential. A full understanding of the processes responsible for the assembly and
      maintenance of the node requires first the identification and characterization of
      the proteins found there. Here we show that NG2, a structurally unique
      chondroitin sulfate proteoglycan, is a molecular component of the node of Ranvier
      in the peripheral nervous system. In adult sciatic nerve, NG2 is (1) associated
      with thin, elongated fibroblast-like cells, (2) on some but not all basal
      laminae, and (3) at nodes of Ranvier. At the nodes, NG2 is restricted to the
      nodal gap and is absent from the paranodal or juxtaparanodal region. In
      dissociated cell cultures of adult sciatic nerve, perineurial fibroblasts but not
      Schwann cells express NG2 on their surfaces. Approximately 45% of the total NG2
      in peripheral nerves is in a soluble, rather than particulate, subcellular
      compartment. NG2 is also present in membrane fractions that also contain high
      levels of voltage-dependent sodium channels, caspr, and neuron-glia related cell
      adhesion molecule. These medium-density membranes likely correspond to the nodal
      and paranodal region of the axon-Schwann cell unit. These results suggest a model
      in which perineurial fibroblasts secrete or shed NG2, which subsequently
      associates with nodes of Ranvier. The growth-inhibitory and anti-adhesive
      properties of NG2 may limit the lateral extension of myelinating Schwann cells as
      nodes mature. NG2 may also participate in the barrier functions of the
      perineurial linings of the nerve.

PMID- 11588185
TI  - Primordial rhythmic bursting in embryonic cochlear ganglion cells.
AB  - This study examined the nature of spontaneous discharge patterns in cochlear
      ganglion cells in embryonic day 13 (E13) to early E17 chicken embryos (stages 39
      43). Neural recordings were made with glass micropipettes. No sound-driven
      activity was seen for the youngest embryos (maximum intensity 107 dB sound
      pressure level). Ganglion cells were labeled with biotinylated dextran amine in
      four embryos. In two animals, primary afferents projected to hair cells in the
      middle region along the length of the basilar papilla in which, in one cell, the
      terminals occupied a neural transverse position and, in the other, a more
      abneural location. Statoacoustic ganglion cells showing no spontaneous activity
      were seen for the first time in the chicken. The proportion of "silent" cells was
      largest at the youngest stages (stage 39, 67%). In active cells, mean spontaneous
      discharge rates [9.4 +/- 10.4 spikes (Sp)/sec; n = 44] were lower than rates for
      older embryos (19 +/- 17 Sp/sec) (Jones and Jones, 2000). Embryos at stages 39-41
      evidenced even lower rates (4.2 +/- 5.0 Sp/sec). The most salient feature of
      spontaneous activity for stages 39-43 was a bursting discharge pattern in >75% of
      active neurons (33 of 44). Moreover, in 55% of these cells, there was a clear,
      slow, rhythmic bursting pattern. The proportion of cells showing rhythmic
      bursting was greatest at the youngest stages (39-42) and decreased to <30% at
      stage 43. Rate of bursting ranged from 1 to 54 bursts per minute. The presence of
      rhythmic bursting in cochlear ganglion cells at E13-E17 provides an explanation
      for the existence of such patterns in central auditory relays. The bursting
      patterns may serve as a patterning signal for central synaptic refinements in the
      auditory system during development.

PMID- 11588186
TI  - Feature selectivity and interneuronal cooperation in the thalamocortical system.
AB  - Action potentials are a universal currency for fast information transfer in the
      nervous system, yet few studies address how some spikes carry more information
      than others. We focused on the transformation of sensory representations in the
      lemniscal (high-fidelity) auditory thalamocortical network. While stimulating
      with a complex sound, we recorded simultaneously from functionally connected cell
      pairs in the ventral medial geniculate body and primary auditory cortex. Thalamic
      action potentials that immediately preceded or potentially caused a cortical
      spike were more selective than the average thalamic spike for spectrotemporal
      stimulus features. This net improvement of thalamic signaling indicates that for
      some thalamic cells, spikes are not propagated through cortex independently but
      interact with other inputs onto the same target cell. We then developed a method
      to identify the spectrotemporal nature of these interactions and found that they
      could be cooperative or antagonistic to the average receptive field of the
      thalamic cell. The degree of cooperativity with the thalamic cell determined the
      increase in feature selectivity for potentially causal thalamic spikes. We
      therefore show how some thalamic spikes carry more receptive field information
      than average and how other inputs cooperate to constrain the information
      communicated through a cortical cell.

PMID- 11588187
TI  - Excitatory and inhibitory circuitry in the superficial gray layer of the superior
      colliculus.
AB  - Stratum griseum superficiale (SGS) of the superior colliculus receives a dense
      cholinergic input from the parabigeminal nucleus. In this study, we examined in
      vitro the modulatory influence of acetylcholine (ACh) on the responses of SGS
      neurons that project to the visual thalamus in the rat. We used whole-cell patch
      clamp recording to measure the responses of these projection neurons to
      electrical stimulation of their afferents in the stratum opticum (SO) before and
      during local pressure injections of ACh. These colliculothalamic projection
      neurons (CTNs) were identified during the in vitro experiments by prelabeling
      them from the thalamus with the retrograde axonal tracer wheat germ agglutinin
      apo-HRP-gold. In a group of cells that included the prelabeled neurons, EPSCs
      evoked by SO stimulation were significantly reduced by the application of ACh,
      whereas IPSC amplitudes were significantly enhanced. Similar effects were
      observed when the nicotinic ACh receptor agonist lobeline was used. Application
      of the selective GABA(B) receptor antagonist 3-[[(3,4-dichlorophenyl)
      methyl]amino]propyl](diethoxymethyl)phosphinic acid blocked ACh-induced reduction
      in the evoked response. In contrast, the ACh-induced reduction was insensitive to
      application of the GABA(A) receptor antagonist bicuculline. The ACh-induced
      reduction was also diminished by bath application of muscimol at the low
      concentrations that selectively activate GABA(C) receptors. Because GABA(C)
      receptors may be specifically expressed by GABAergic SGS interneurons (Schmidt et
      al., 2001), our results support the hypothesis that ACh reduces CTN activity by
      nicotinic receptor-mediated excitation of local GABAergic interneurons. These
      interneurons in turn use GABA(B) receptors to inhibit the CTNs.

PMID- 11588188
TI  - Decreased glutamate receptor 2 expression and enhanced epileptogenesis in
      immature rat hippocampus after perinatal hypoxia-induced seizures.
AB  - Hypoxic encephalopathy is the most common cause of neonatal seizures and can lead
      to chronic epilepsy. In rats at postnatal days 10-12 (P10-12), global hypoxia
      induces spontaneous seizures and chronically decreases seizure threshold, thus
      mimicking clinical aspects of neonatal hypoxia. We have shown previously that the
      acute and chronic epileptogenic effects of hypoxia are age-dependent and require
      AMPA receptor activation. In this study, we aimed to determine whether hypoxia
      induced seizures and epileptogenesis are associated with maturational and seizure
      induced changes in AMPA receptor composition and function. Northern and Western
      blots indicated that glutamate receptor 2 (GluR2) mRNA and protein expression
      were significantly lower in neocortex and hippocampus at P10-12 compared with
      adult. After hypoxia-induced seizures at P10, GluR2 mRNA was significantly
      decreased within 48 hr, and GluR2 protein was significantly decreased within 96
      hr. AMPA-induced Co(2+) uptake by neurons in hippocampal slices indicated higher
      expression of Ca(2+)-permeable AMPA receptors in immature pyramidal neurons
      compared with adult. In slices obtained 96 hr after hypoxia-induced seizures,
      AMPA-induced Co(2+) uptake was significantly increased compared with age-matched
      controls, and field recordings revealed increased tetanus-induced afterdischarges
      that could be kindled in the absence of NMDA receptor activation. In situ end
      labeling showed no acute or delayed cell death after hypoxia-induced seizures.
      Our results indicate that susceptibility to hypoxia-induced seizures occurs
      during a developmental stage in which the expression of Ca(2+)-permeable AMPA
      receptors is relatively high. Furthermore, perinatal hypoxia-induced seizures
      induce increased expression of Ca(2+)-permeable AMPA receptors and an increased
      capacity for AMPA receptor-mediated epileptogenesis without inducing cell death.

PMID- 11588189
TI  - Selective immunolesions of cholinergic neurons in mice: effects on neuroanatomy,
      neurochemistry, and behavior.
AB  - The ability to selectively lesion mouse basal forebrain cholinergic neurons would
      permit experimental examination of interactions between cholinergic functional
      loss and genetic factors associated with neurodegenerative disease. We developed
      a selective toxin for mouse basal forebrain cholinergic neurons by conjugating
      saporin (SAP), a ribosome-inactivating protein, to a rat monoclonal antibody
      against the mouse p75 nerve growth factor (NGF) receptor (anti-murine-p75). The
      toxin proved effective and selective in vitro and in vivo.
      Intracerebroventricular injections of anti-murine-p75-SAP produced a dose
      dependent loss of choline acetyltransferase (ChAT) activity in the hippocampus
      and neocortex without affecting glutamic acid decarboxylase (GAD) activity.
      Hippocampal ChAT depletions induced by the immunotoxin were consistently greater
      than neocortical depletions. Immunohistochemical analysis revealed a dose
      dependent loss of cholinergic neurons in the medial septum (MS) but no marked
      loss of cholinergic neurons in the nucleus basalis magnocellularis after
      intracerebroventricular injection of the toxin. No loss of noncholinergic neurons
      in the MS was apparent, nor could we detect loss of noncholinergic cerebellar
      Purkinje cells, which also express p75. Behavioral analysis suggested a spatial
      learning deficit in anti-murine-p75-SAP-lesioned mice, based on a correlation
      between a loss of hippocampal ChAT activity and impairment in Morris water maze
      performance. Our results indicate that we have developed a specific cholinergic
      immunotoxin for mice. They also suggest possible functional differences in the
      mouse and rat cholinergic systems, which may be of particular significance in
      attempts to develop animal models of human diseases, such as Alzheimer's disease,
      which are associated with impaired cholinergic function.

PMID- 11588190
TI  - From three-dimensional space vision to prehensile hand movements: the lateral
      intraparietal area links the area V3A and the anterior intraparietal area in
      macaques.
AB  - The posterior parietal cortex is included in the dorsal cortical visual pathway
      underlying the three-dimensional (3-D) visual recognition of space and objects.
      The neurons in the lateral intraparietal area (LIP) respond visually to the three
      dimensional objects, whereas those in the anterior intraparietal area (AIP)
      respond to hand movements to grasp them. LIP receives visual inputs from V3A,
      whereas AIP projects to the premotor areas; however, it is not known whether the
      neurons in LIP project to AIP. We herein investigated the connectional substrates
      that underlie the transformation of three-dimensional vision to prehensile hand
      movements in the Japanese monkey (Macaca fuscata). After identifying the three
      dimensional visually responsive region in the posterior part of LIP by the unit
      recordings, we injected a bidirectional tracer, wheat germ agglutinin conjugated
      to horseradish peroxidase, into one of the recording sites. We found that LIP
      receives neuronal projections from V3A and sends axons to AIP. To confirm our
      findings, we injected several orthograde tracers into V3A and retrograde tracers
      into AIP in the same hemispheres. We found that the V3A neurons projecting to LIP
      terminate in the vicinity of the LIP neurons projecting to AIP. The results
      suggest that the cortical connections of V3A-LIP-AIP in the lateral bank of the
      intraparietal sulcus play an important role in the visuomotor transformation for
      prehensile hand movements.

PMID- 11588191
TI  - 5-hydroxytryptamine (5-HT)1A autoreceptor adaptive changes in substance P
      (neurokinin 1) receptor knock-out mice mimic antidepressant-induced
      desensitization.
AB  - Antagonists at substance P receptors of the neurokinin 1 (NK1) type have been
      shown to represent a novel class of antidepressant drugs, with comparable
      clinical efficacy to the selective serotonin (5-HT) reuptake inhibitors (SSRIs).
      Because 5-HT(1A) receptors may be critically involved in the mechanisms of action
      of SSRIs, we examined whether these receptors could also be affected in a model
      of whole-life blockade of NK1 receptors, i.e. knock-out mice lacking the latter
      receptors (NK1-/-). 5-HT(1A) receptor labeling by the selective antagonist
      radioligand [(3)H]N-[2-[4-(2-methoxyphenyl)1-piperazinyl]-ethyl]-N-(2-pyridinyl)
      cyclohexanecarboxamide (WAY 100635) and 5-HT(1A)-dependent [(35)S]GTP-gamma-S
      binding at the level of the dorsal raphe nucleus (DRN) in brain sections, as well
      as the concentration of 5-HT(1A) mRNA in the anterior raphe area were
      significantly reduced (-19 to -46%) in NK1-/- compared with NK1+/+ mice.
      Furthermore, a approximately 10-fold decrease in the potency of the 5-HT(1A)
      receptor agonist ipsapirone to inhibit the discharge of serotoninergic neurons in
      the dorsal raphe nucleus within brainstem slices, and reduced hypothermic
      response to 8-OH-DPAT, were noted in NK1-/- versus NK1+/+ mice. On the other
      hand, cortical 5-HT overflow caused by systemic injection of the SSRI paroxetine
      was four- to sixfold higher in freely moving NK1-/- mutants than in wild-type
      NK1+/+ mice. Accordingly, the constitutive lack of NK1 receptors appears to be
      associated with a downregulation/functional desensitization of 5-HT(1A)
      autoreceptors resembling that induced by chronic treatment with SSRI
      antidepressants. Double immunocytochemical labeling experiments suggest that such
      a heteroregulation of 5-HT(1A) autoreceptors in NK1-/- mutants does not reflect
      the existence of direct NK1-5-HT(1A) receptor interactions in normal mice.

PMID- 11588193
TI  - Consistency of encoding in monkey visual cortex.
AB  - Are different kinds of stimuli (for example, different classes of geometric
      images or naturalistic images) encoded differently by visual cortex, or are the
      principles of encoding the same for all stimuli? We examine two response
      properties: (1) the range of spike counts that can be elicited from a neuron in
      epochs representative of short periods of fixation (up to 400 msec), and (2) the
      relation between mean and variance of spike counts elicited by different stimuli,
      that together characterize the information processing capabilities of a neuron
      using the spike count code. In monkey primary visual cortex (V1) complex cells,
      we examine responses elicited by static stimuli of four kinds (photographic
      images, bars, gratings, and Walsh patterns); in area TE of inferior temporal
      cortex, we examine responses elicited by static stimuli in the sample, nonmatch,
      and match phases of a delayed match-to-sample task. In each area, the ranges of
      mean spike counts and the relation between mean and variance of spike counts
      elicited are sufficiently similar across experimental conditions that information
      transmission is unaffected by the differences across stimulus set or behavioral
      conditions [although in 10 of 27 (37%) of the V1 neurons there are statistically
      significant but small differences, the median difference in transmitted
      information for these neurons was 0.9%]. Encoding therefore appears to be
      consistent across experimental conditions for neurons in both V1 and TE, and
      downstream neurons could decode all incoming signals using a single set of rules.

PMID- 11588192
TI  - Age-dependent cognitive deficits and neuronal apoptosis in cyclooxygenase-2
      transgenic mice.
AB  - The cyclooxygenases catalyze the rate-limiting step in the formation of
      prostaglandins from arachidonic acid and are the pharmacological targets of
      (NSAIDs). In brain, cyclooxygenase-2 (COX-2), the inducible isoform of
      cyclooxygenase, is selectively expressed in neurons of the cerebral cortex,
      hippocampus, and amygdala. As an immediate-early gene, COX-2 is dramatically and
      transiently induced in these neurons in response to NMDA receptor activation. In
      models of acute excitotoxic neuronal injury, elevated and sustained levels of COX
      2 have been shown to promote neuronal apoptosis, indicating that upregulated COX
      2 activity is injurious to neurons. COX-2 may also contribute to the development
      of Alzheimer's disease, for which early administration of NSAIDs is protective
      against development of the disease. To test the effect of constitutively elevated
      neuronal COX-2, transgenic mice were generated that overexpressed COX-2 in
      neurons and produced elevated levels of prostaglandins in brain. In cross
      sectional behavioral studies, COX-2 transgenic mice developed an age-dependent
      deficit in spatial memory at 12 and 20 months but not at 7 months and a deficit
      in aversive behavior at 20 months of age. These behavioral changes were
      associated with a parallel age-dependent increase in neuronal apoptosis occurring
      at 14 and 22 months but not at 8 months of age and astrocytic activation at 24
      months of age. These findings suggest that neuronal COX-2 may contribute to the
      pathophysiology of age-related diseases such as Alzheimer's disease by promoting
      memory dysfunction, neuronal apoptosis, and astrocytic activation in an age
      dependent manner.

PMID- 11588194
TI  - Encoding of direction of fingertip forces by human tactile afferents.
AB  - In most manipulations, we use our fingertips to apply time-varying forces to the
      target object in controlled directions. Here we used microneurography to assess
      how single tactile afferents encode the direction of fingertip forces at
      magnitudes, rates, and directions comparable to those arising in everyday
      manipulations. Using a flat stimulus surface, we applied forces to a standard
      site on the fingertip while recording impulse activity in 196 tactile afferents
      with receptive fields distributed over the entire terminal phalanx. Forces were
      applied in one of five directions: normal force and forces at a 20 degrees angle
      from the normal in the radial, distal, ulnar, or proximal directions. Nearly all
      afferents responded, and the responses in most slowly adapting (SA)-I, SA-II, and
      fast adapting (FA)-I afferents were broadly tuned to a preferred direction of
      force. Among afferents of each type, the preferred directions were distributed in
      all angular directions with reference to the stimulation site, but not uniformly.
      The SA-I population was biased for tangential force components in the distal
      direction, the SA-II population was biased in the proximal direction, and the FA
      I population was biased in the proximal and radial directions. Anisotropic
      mechanical properties of the fingertip and the spatial relationship between the
      receptive field center of the afferent and the stimulus site appeared to
      influence the preferred direction in a manner dependent on afferent type. We
      conclude that tactile afferents from the whole terminal phalanx potentially
      contribute to the encoding of direction of fingertip forces similar to those that
      occur when subjects manipulate objects under natural conditions.

PMID- 11588195
TI  - Reduction in opioid- and cannabinoid-induced antinociception in rhesus monkeys
      after bilateral lesions of the amygdaloid complex.
AB  - The amygdaloid complex is a prominent temporal lobe region that is associated
      with "emotional" information processing. Studies in the rodent have also recently
      implicated the amygdala in the processing and modulation of pain sensation, the
      experience of which involves a considerable emotional component in humans. In the
      present study, we sought to establish the relevance of the amygdala to pain
      modulation in humans by investigating the contribution of this region to
      antinociceptive processes in nonhuman primates. Using magnetic resonance imaging
      guidance, the amygdaloid complex was lesioned bilaterally in six rhesus monkeys
      (Macaca mulatta) through microinjection of the neurotoxin ibotenic acid. This
      procedure resulted in substantial neuronal cell loss in all nuclear subdivisions
      of this structure. In awake unoperated control monkeys, systemic administration
      of the prototypical opioid morphine or the cannabinoid receptor agonist WIN55,212
      2 produced dose-dependent antinociception on a warm-water tail-withdrawal assay.
      The antinociceptive effects of each drug were reversible with an appropriate
      antagonist. In monkeys with bilateral amygdala lesions, however, the
      antinociceptive effects of each drug were significantly reduced. These results
      constitute the first causal data demonstrating the necessity of neurons in a
      specific brain region for the full expression of opioid- and cannabinoid-induced
      antinociception in the primate. Because our amygdala-lesioned monkeys exhibited
      both a reduction in antinociception and a reduction in behavioral indices of fear
      (Emery et al., 2001), the possibility should be considered that, in the primate,
      "antinociceptive circuitry" and "fear circuitry" overlap at the level of the
      amygdala.

PMID- 11588197
TI  - The topography of tactile working memory.
AB  - To investigate the contribution of topographically organized brain areas to
      tactile working memory, we asked human subjects to compare the frequency of two
      vibrations presented to the same fingertip or to different fingertips. The
      vibrations ranged from 14 to 24 Hz and were separated by a retention interval of
      variable length. For intervals <1 sec, subjects were accurate when both
      vibrations were delivered to the same fingertip but were less accurate when the
      two vibrations were delivered to different fingertips. For 1 or 2 sec intervals,
      subjects performed equally well when comparing vibrations delivered either to the
      same finger or to corresponding fingers on opposite hands, but they performed
      poorly when the vibrations were delivered to distant fingers on either hand.
      These results suggest that working memory resides within a topographic framework.
      As a further test, we performed an experiment in which the two comparison
      vibrations were presented to the same fingertip but an interference vibration was
      presented during the retention interval. The interpolated vibration disrupted
      accuracy most when delivered to the same finger as the comparison vibrations and
      had progressively less effect when delivered to more distant fingers. We conclude
      that topographically organized regions of somatosensory cortex contribute to
      tactile working memory, possibly by holding the memory trace across the retention
      interval. One stimulus can be accurately compared with the memory of a previous
      stimulus if they engage overlapping representations, but activation of the common
      cortical territory by an interpolated stimulus can disrupt the memory trace.

PMID- 11588196
TI  - The enterins: a novel family of neuropeptides isolated from the enteric nervous
      system and CNS of Aplysia.
AB  - To identify neuropeptides that have a broad spectrum of actions on the feeding
      system of Aplysia, we searched for bioactive peptides that are present in both
      the gut and the CNS. We identified a family of structurally related nonapeptides
      and decapeptides (enterins) that are present in the gut and CNS of Aplysia, and
      most of which share the HSFVamide sequence at the C terminus. The structure of
      the enterin precursor deduced from cDNA cloning predicts 35 copies of 20
      different enterins. Northern analysis, in situ hybridization, and
      immunocytochemistry show that the enterins are abundantly present in the CNS and
      the gut of Aplysia. Using matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry we characterized the enterin-precursor processing,
      demonstrated that all of the precursor-predicted enterins are present, and
      determined post-translational modifications of various enterins. Enterin-positive
      neuronal somata and processes were found in the gut, and enterins inhibited
      contractions of the gut. In the CNS, the cerebral and buccal ganglia, which
      control feeding, contained the enterins. Enterin was also present in the nerve
      that connects these two ganglia. Enterins reduced the firing of interneurons B4/5
      during feeding motor programs. Such enterin-induced reduction of firing also
      occurred when excitability of B4/5 was tested directly. Because reduction of B4/5
      activity corresponds to a switch from egestive to ingestive behaviors, enterin
      may contribute to such program switching. Furthermore, because enterins are
      present throughout the nervous system, they may also play a regulatory role in
      nonfeeding behaviors of Aplysia.

PMID- 11588199
TI  - Oxytocin in the medial amygdala is essential for social recognition in the mouse.
AB  - Oxytocin (OT) knock-out mice fail to recognize familiar conspecifics after
      repeated social exposures, despite normal olfactory and spatial learning
      abilities. OT treatment fully restores social recognition. Here we demonstrate
      that OT acts in the medial amygdala during the initial exposure to facilitate
      social recognition. OT given before, but not after, the initial encounter
      restores social recognition in OT knock-out mice. Using c-Fos immunoreactivity
      (Fos-IR) as a marker of neuronal activation in this initial encounter, we found
      similar neuronal activation in the wild-type (WT) and OT knock-out mouse in
      olfactory bulbs, piriform cortex, cortical amygdala, and the lateral septum. Wild
      type, but not OT knock-out mice exhibited an induction of Fos-IR in the medial
      amygdala. Projections sites of the medial amygdala also failed to show a Fos-IR
      induction in the OT knock-out mice. OT knock-out, but not WT, mice showed
      dramatic increases in Fos-IR in the somatosensory cortex and the hippocampus,
      suggesting alternative processing of social cues in these animals. With site
      specific injections of OT and an OT antagonist, we demonstrate that OT receptor
      activation in the medial amygdala is both necessary and sufficient for social
      recognition in the mouse.

PMID- 11588198
TI  - Coincident spiking activity induces long-term changes in inhibition of
      neocortical pyramidal cells.
AB  - In pyramidal cells, induction of long-term potentiation (LTP) and long-term
      depression (LTD) of excitatory synaptic transmission by coincidence of
      presynaptic and postsynaptic activity is considered relevant to learning
      processes in vivo. Here we show that temporally correlated spiking activity of a
      pyramidal cell and an inhibiting interneuron may cause LTD or LTP of unitary
      IPSPs. Polarity of change in synaptic efficacy depends on timing between Ca(2+)
      influx induced by a backpropagating train of action potentials (APs) in pyramidal
      cell dendrites (10 APs, 50 Hz) and subsequent activation of inhibitory synapses.
      LTD of IPSPs was induced by synaptic activation in the vicinity of the AP train
      (<300 msec relative to the beginning of the train), whereas LTP of IPSPs was
      initiated with more remote synaptic activation (>400 msec relative to the
      beginning of the AP train). Solely AP trains induced neither LTP nor LTD. Both
      LTP and LTD were prevented by 5 mm BAPTA loaded into pyramidal cells. LTD was
      prevented by 5 mm EGTA, whereas EGTA failed to affect LTP. Synaptic plasticity
      was not dependent on activation of GABA(B) receptors. It was also not affected by
      the antagonists of vesicular exocytosis, botulinum toxin D, and GDP-beta-S.

PMID- 11588200
TI  - Functional retinotopy of monkey visual cortex.
AB  - The operations of primary visual cortex generate continuous representations of
      orientation, ocular dominance, and retinotopy that, to fit in two dimensions,
      organize at separate but overlapping scales (e.g., 20-500 microm, 200 microm to 5
      mm, and 2-33 mm). Where their scales overlap, these organizations interact; iso
      orientation contours cross ocular dominance columns at right angles, and ocular
      dominance columns distort retinotopy near the V1/V2 border. To explore these
      interactions, we developed an optical technique for visualizing retinotopy in
      vivo that allows us to analyze it in relation to ocular dominance and orientation
      patterns. Our results show local retinotopic distortions in every region of
      macaque V1 that we examine, including regions far from the V1/V2 border. They
      also show a consistent relation between local axes of distortion and ocular
      dominance slabs, which they intersect at angles of approximately 90 degrees. A
      further correlation is provided by retinotopic maps from New World primates that
      show less distortion (9 vs 60%) in two species characterized by an absence of
      pronounced ocular dominance columns. Retinotopic maps from these New World
      primates also revealed an unexpected tilt of the vertical midline representation
      that diverged from the V1/V2 border by an angle of approximately 20 degrees.
      Overall, these results suggest a general tendency for slab-based organizations to
      distort retinotopy by representing the same part of space more than once in
      adjacent slabs.

PMID- 11588201
TI  - Protection by pyruvate against transient forebrain ischemia in rats.
AB  - Pyruvate has a remarkable protective effect against zinc neurotoxicity. Because
      zinc neurotoxicity is likely one of the key mechanisms of ischemic brain injury,
      the neuroprotective effect of pyruvate was tested in a rat model of transient
      forebrain ischemia. Control experiments in mouse cortical culture showed that
      pyruvate almost completely blocked zinc toxicity but did not attenuate calcium
      overload neuronal death. Adult rats subjected to 12 min forebrain ischemia
      exhibited widespread zinc accumulation and neuronal death throughout hippocampus
      and cortex 72 hr after reperfusion. However, rats injected intraperitoneally with
      sodium pyruvate (500-1000 mg/kg) within 1 hr after 12 min forebrain ischemia
      showed almost no neuronal death. In addition, the mortality was markedly
      decreased in the pyruvate-protected groups (3.8%) compared with the NaCl-injected
      control group (58.1%). The neuroprotective effect persisted even at 30 d after
      the insult. The spectacular protection without noticeable side effects makes
      pyruvate a promising neuroprotectant in human ischemic stroke.

PMID- 11588202
TI  - Motion-induced perceptual extrapolation of blurred visual targets.
AB  - In the motion-extrapolation hypothesis, the visual system can extrapolate the
      instantaneous position of a moving object from its past trajectory. The existence
      of such a mechanism in human vision has been intensely debated. Here, we show
      compelling perceptual extrapolation of both first- and second-order moving
      stimuli, the magnitude of which depends on blurring of the visual target. The
      spatiotemporal characteristics of the extrapolation can be quantitatively
      accounted for by a simple model based on temporally biphasic neuronal response, a
      property widely observed among sensory neurons. Thus, motion-induced perceptual
      extrapolation exists in human vision, and spatial blurring is an important factor
      in the interaction between motion and perceptual localization.

PMID- 11588203
TI  - Ephaptic interactions in the mammalian olfactory system.
AB  - Ephaptic coupling refers to interactions between neurons mediated by current flow
      through the extracellular space. Ephaptic interactions between axons are
      considered negligible, because of the relatively large extracellular space and
      the layers of myelin that separate most axons. By contrast, olfactory nerve axons
      are unmyelinated and arranged in tightly packed bundles, features that may
      enhance ephaptic coupling. We tested the hypothesis that ephaptic interactions
      occur in the mammalian olfactory nerve with the use of a computational approach.
      Numerical solutions of models of axon fascicles show that significant ephaptic
      interactions occur for a range of physiologically relevant parameters. An action
      potential in a single axon can evoke action potentials in all other axons in the
      fascicle. Ephaptic interactions can also lead to synchronized firing of
      independently stimulated axons. Our findings suggest that ephaptic interactions
      may be significant determinants of the olfactory code and that such interactions
      may occur in other, similarly organized axonal or dendritic bundles.

PMID- 11588204
TI  - Cerebellar depolarization-induced suppression of inhibition is mediated by
      endogenous cannabinoids.
AB  - Depolarization of cerebellar Purkinje neurons transiently suppresses IPSCs
      through a process known as depolarization-induced suppression of inhibition
      (DSI). This IPSC suppression occurs presynaptically and results from an unknown
      retrograde signal released from Purkinje cells. We recorded IPSCs from voltage
      clamped Purkinje cells in cerebellar brain slices to identify the retrograde
      signal for cerebellar DSI. We find that DSI persists in the presence of the broad
      spectrum metabotropic glutamate receptor antagonist LY341495 and the GABA(B)
      receptor antagonist CGP55845, suggesting that the retrograde signal is not acting
      through these receptors. However, an antagonist of the cannabinoid CB1 receptor
      AM251 completely blocked cerebellar DSI. Additionally, the cannabinoid receptor
      agonist WIN55,212-2 suppressed IPSCs and occluded any additional IPSC reduction
      by DSI. These results indicate that cannabinoids released from Purkinje cells
      after depolarization activate CB1 receptors on inhibitory neurons and suppress
      IPSCs for tens of seconds. Cerebellar DSI thus shares a common retrograde
      messenger with DSI in the hippocampus and depolarization-induced suppression of
      excitation in the cerebellum, suggesting that retrograde synaptic suppression by
      endogenous cannabinoids represents a widespread signaling mechanism.

PMID- 11588205
TI  - Somatic colocalization of rat SK1 and D class (Ca(v)1.2) L-type calcium channels
      in rat CA1 hippocampal pyramidal neurons.
AB  - In hippocampal neurons, the firing of a train of action potentials is terminated
      by generation of the slow afterhyperpolarization (AHP). Recordings from
      hippocampal slices have shown that the slow AHP likely results from the
      activation of small-conductance calcium-activated potassium (SK) channels by
      calcium (Ca(2+)) entry through L-type Ca(2+) channels. However, the relative
      localization of these two channel subtypes is not known. The cloning and
      characterization of three subtypes of SK channel has suggested that SK1 may
      underlie generation of the slow AHP. Using a novel antibody directed against rat
      SK1 (rSK1), it has been determined that the rSK1 channel is primarily in the soma
      of hippocampal CA1 neurons. In conjunction with antibodies directed against C
      (Ca(v)1.2) and D (Ca(v)1.3) class L-type Ca(2+) channel alpha1 subunits, it was
      observed that rSK1 channels were selectively colocalized with D class L-type
      channels. This colocalization supports the functional coupling of L-type and SK
      channels previously observed in cell-attached patches from hippocampal neurons.
      However, it appears contrary to the slow rise and decay of the slow AHP.
      Induction of delayed facilitation of L-type Ca(2+) channels in cell-attached
      patches from hippocampal neurons evoked delayed opening of coupled SK channels.
      Generation of ensemble currents produced waveforms identical to the ionic current
      underlying the slow AHP (I(sAHP)). Therefore, these data indicate that the slow
      AHP is somatic in origin, resulting from delayed facilitation of D class L-type
      Ca(2+) channels colocalized with rSK1 channels.

PMID- 11588206
TI  - 17-beta-estradiol induces an inhibitor of active caspases.
AB  - We have shown previously that caspase-6 activity is lethal to human neurons
      (LeBlanc et al., 1999; Zhang et al., 2000). Here we find that 17-beta-estradiol
      but not 17-alpha-estradiol prevents caspase-6-mediated neuronal cell death. 17
      beta-estradiol-treated neuronal extracts directly inhibit recombinant active
      caspase-6, caspase-3, caspase-7, and caspase-8 in vitro. We conclude that 17-beta
      estradiol induces a caspase inhibitory factor (CIF) that is preventing neuronal
      apoptosis. The induction of CIF occurs within 10 min of 17-beta-estradiol
      exposure to neurons, does not require de novo protein synthesis, and involves
      mitogen-activated protein kinase activation. The effect is antagonized by the
      estrogen receptor antagonist tamoxifen. In contrast, 17-beta-estradiol does not
      induce CIF or prevent caspase-mediated cell death in cultured astrocytes. CIF
      does not act through oxidation of the caspase active site. CIF activity
      copurifies with proteins of between 12 and 14 kDa in size. Our results indicate
      that 17-beta-estradiol induces an inhibitor of active caspases through a receptor
      mediated nongenomic pathway and provide an additional mechanism for the
      neuroprotective action of 17-beta-estradiol that is likely highly relevant to the
      understanding of the role of estrogen against Alzheimer's disease.

PMID- 11588207
TI  - Oscillatory synchrony between human extrastriate areas during visual short-term
      memory maintenance.
AB  - How do we keep an object in mind? Based on evidence from animal electrophysiology
      and human brain-imaging techniques, it is commonly held that short-term memory
      relies on sustained activity in a network distributed over sensory and prefrontal
      cortices. How does neural firing persist in such a distributed network in the
      absence of visual input? Hebb's influential but so far unproved proposal,
      developed more than 50 years ago, is that sustained activation in short-term
      memory networks is maintained by reverberating activity in neuronal loops. We
      hypothesized that synchronized oscillatory activity, proposed to provide a
      dynamic link between distributed areas, could not only coordinate activity in the
      network but also establish reentrant loops in the system to enable both sustained
      firing and temporal coincidence of inputs. We show in human intracranial
      recordings that limited regions of extrastriate visual areas, separated by
      several centimeters, become synchronized in an oscillatory mode during the
      rehearsal of an object in visual short-term memory. Synchrony occurs specifically
      in the beta range (15-25 Hz) and disappears in a control condition. These
      findings thus confirm experimentally the hypothesis of a functional role of
      synchronized oscillatory activity in the coordination of distributed neural
      activity in humans, and support Hebb's popular but unproved concept of short-term
      memory maintenance by reentrant activity within the activated network.

PMID- 11588208
TI  - The critically ill: following your MEWS.

PMID- 11588209
TI  - Screening for subclinical deep-vein thrombosis.

PMID- 11588210
TI  - Validation of a modified Early Warning Score in medical admissions.
AB  - The Early Warning Score (EWS) is a simple physiological scoring system suitable
      for bedside application. The ability of a modified Early Warning Score (MEWS) to
      identify medical patients at risk of catastrophic deterioration in a busy
      clinical area was investigated. In a prospective cohort study, we applied MEWS to
      patients admitted to the 56-bed acute Medical Admissions Unit (MAU) of a District
      General Hospital (DGH). Data on 709 medical emergency admissions were collected
      during March 2000. Main outcome measures were death, intensive care unit (ICU)
      admission, high dependency unit (HDU) admission, cardiac arrest, survival and
      hospital discharge at 60 days. Scores of 5 or more were associated with increased
      risk of death (OR 5.4, 95%CI 2.8-10.7), ICU admission (OR 10.9, 95%CI 2.2-55.6)
      and HDU admission (OR 3.3, 95%CI 1.2-9.2). MEWS can be applied easily in a DGH
      medical admission unit, and identifies patients at risk of deterioration who
      require increased levels of care in the HDU or ICU. A clinical pathway could be
      created, using nurse practitioners and/or critical care physicians, to respond to
      high scores and intervene with appropriate changes in clinical management.

PMID- 11588211
TI  - Prevalence and significance of the familial Mediterranean fever gene mutation
      encoding pyrin Q148.
AB  - Familial Mediterranean fever (FMF) is caused by more than 25 mutations in the
      gene MEFV, which encodes pyrin (marenostrin), a protein implicated in the
      regulation of neutrophil activity. Pyrin Q148, is one of the five most common
      variants in populations in which FMF typically occurs. Our identification of the
      pyrin Q148 allele in several patients from ethnic groups in which FMF is not
      classically recognized who had longstanding fevers or AA amyloidosis prompted us
      to study the prevalence of pyrin Q148 in healthy British, Indian and Chinese
      subjects. The gene frequency was also sought in 50 British Caucasian patients
      with inflammatory arthritis, 25 of whom had AA amyloidosis, five Punjabi Indians
      with AA amyloidosis complicating inflammatory arthritis, and seven British
      Caucasian patients with uncharacterized longstanding fever syndromes. The allele
      frequency for pyrin Q148 was 21%, 15% and 0%, respectively, among Punjabi Indian,
      Chinese and Caucasian British controls, and was significantly increased among the
      patients with AA amyloidosis and the patients with obscure fever syndromes
      (p<0.01). Pyrin Q148 is a polymorphism and occurs widely in global terms, and,
      although it may cause FMF when associated with certain other MEFV mutations,
      homozygosity for Q148 alone must usually be insufficient to produce FMF in the
      populations studied. The association of pyrin Q148 with AA amyloidosis and with
      obscure chronic inflammatory diseases suggests the variant may augment
      inflammation non-specifically, which might have been beneficial during evolution,
      but could potentially exacerbate many chronic inflammatory disorders.

PMID- 11588212
TI  - Non-specialist management of acute renal failure.
AB  - In a 12-month prospective study of the initial management of patients with acute
      renal failure (ARF) in East Kent (population 593 000), we evaluated the initial
      management of ARF and assessed what proportion of ARF may have been preventable.
      Patients were seen and assessed on a daily basis, and were followed until
      discharge from hospital or death; survivors were subsequently followed for 3
      years. Overall, 288 patients developed ARF (486 per million population/year).
      Mean age at presentation was 73 years (range 14-96). Initial assessment was often
      suboptimal, and key features in investigation and initial management were often
      lacking. In 108 cases, ARF was iatrogenic and/or potentially preventable (53
      preventable, 99 iatrogenic, 44 both). Overall survival was 56% at discharge from
      hospital, 35% at 1-year follow-up, 31% at 2 years, and 28% at 3 years. In
      discharged patients, recovery of function was complete in 69%. A significant
      proportion of ARF is preventable. Clear guidelines, easily accessible at the
      point of care, could aid the diagnostic evaluation of the patient with ARF and
      indicate where referral for a specialist opinion is appropriate.

PMID- 11588213
TI  - Factors affecting renal function in 119 985 adults over three years.
AB  - Blood pressure, proteinuria and serum creatinine (SCr) were examined in 119 985
      adults, aged 40 years and older, who attended annual health examinations both in
      1993 and 3 years later. Renal function was assessed from SCr; changes in
      individuals' renal function were estimated using the slope of the regression line
      for the reciprocal of the SCr level vs. time (slope of rSCr) over the 3-year
      period. Age-dependent SCr concentration increments were observed; however, there
      was no significant age-dependent change in the slope of rSCr. SCr in
      hypertensives on anti-hypertensive medication was significantly higher than that
      in untreated hypertensives, borderline hypertensives and normotensives. The
      slopes of rSCr in hypertensives (treated, untreated and borderline) were steeper
      than normotensives in males, and that in untreated hypertensives was steeper than
      other groups in females. In hypertensives with proteinuria, SCr was higher and
      renal function deteriorated more rapidly, compared with hypertensives without
      proteinuria. Hypertension with proteinuria appears to be an important indicator
      for progressive decline in renal function, this trend being more obvious in
      males. Renal function decreases with age; however, the rate of decline is
      constant. The influences of proteinuria and blood pressure on renal function are
      different in males and females.

PMID- 11588214
TI  - Coagulopathy following lethal and non-lethal envenoming of humans by the South
      American rattlesnake (Crotalus durissus) in Brazil.
AB  - The South American tropical rattlesnake (Crotalus durissus subspp) is responsible
      for approximately 10% of bites from venomous snakes in Brazil. We studied 24
      victims of bites by this species over 3 years, in south-eastern Brazil,
      particularly investigating haemostatic alterations. Thirteen patients were
      defined as moderately envenomed and 11 as severe. There were two deaths, which
      were not attributed to venom-induced haemostatic disturbances. However,
      envenoming by C. durissus is frequently associated with haemostatic disorders,
      which are probably attributable mainly to the action of the thrombin-like enzyme,
      with possible additional effects secondary to the powerful myotoxic activity of
      the venom.

PMID- 11588215
TI  - Helicobacter pylori--an African perspective.
AB  - Helicobacter pylori is ubiquitous in Africa, with acquisition in childhood the
      rule. Despite the prevalence of a virulent strain (in Soweto, most H. pylori
      organisms are cagA- and vacAS(1)-positive) H. pylori-associated pathology
      (duodenal ulcer, gastric ulcer and gastric cancer) has a variable, often low
      distribution in sub-Saharan Africa that does not parallel H. pylori prevalence in
      the population, suggesting a different natural history from that seen in
      developed countries. Progression to atrophic gastritis in Africans does not
      appear to differ from that reported in other regions, but as yet unidentified
      factors may play a role in inhibiting progression to gastric cancer. Studies have
      suggested that the specific IgG subclass response to H. pylori is predominately
      IgG1 (suggestive of a Th2 response), and the Th2 response may provide a
      protective effect against development of gastric cancer. Host immune mechanisms
      may be the key to different responses to H. pylori in the developed and
      developing worlds.

PMID- 11588216
TI  - Consultant appraisal.

PMID- 11588217
TI  - Antidepressants and side-effects.

PMID- 11588218
TI  - Liver biopsy is not useful in the diagnosis of adult Still's disease.

PMID- 11588220
TI  - Logic circuits with carbon nanotube transistors.
AB  - We demonstrate logic circuits with field-effect transistors based on single
      carbon nanotubes. Our device layout features local gates that provide excellent
      capacitive coupling between the gate and nanotube, enabling strong electrostatic
      doping of the nanotube from p-doping to n-doping and the study of the
      nonconventional long-range screening of charge along the one-dimensional
      nanotubes. The transistors show favorable device characteristics such as high
      gain (>10), a large on-off ratio (>10(5)), and room-temperature operation.
      Importantly, the local-gate layout allows for integration of multiple devices on
      a single chip. Indeed, we demonstrate one-, two-, and three-transistor circuits
      that exhibit a range of digital logic operations, such as an inverter, a logic
      NOR, a static random-access memory cell, and an ac ring oscillator.

PMID- 11588219
TI  - Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic
      receptor and beta-arrestin.
AB  - Although trafficking and degradation of several membrane proteins are regulated
      by ubiquitination catalyzed by E3 ubiquitin ligases, there has been little
      evidence connecting ubiquitination with regulation of mammalian G protein
      (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR)
      function. Agonist stimulation of endogenous or transfected beta2-adrenergic
      receptors (beta2ARs) led to rapid ubiquitination of both the receptors and the
      receptor regulatory protein, beta-arrestin. Moreover, proteasome inhibitors
      reduced receptor internalization and degradation, thus implicating a role for the
      ubiquitination machinery in the trafficking of the beta2AR. Receptor
      ubiquitination required beta-arrestin, which bound to the E3 ubiquitin ligase
      Mdm2. Abrogation of beta-arrestin ubiquitination, either by expression in Mdm2
      null cells or by dominant-negative forms of Mdm2 lacking E3 ligase activity,
      inhibited receptor internalization with marginal effects on receptor degradation.
      However, a beta2AR mutant lacking lysine residues, which was not ubiquitinated,
      was internalized normally but was degraded ineffectively. These findings
      delineate an adapter role of beta-arrestin in mediating the ubiquitination of the
      beta2AR and indicate that ubiquitination of the receptor and of beta-arrestin
      have distinct and obligatory roles in the trafficking and degradation of this
      prototypic GPCR.

PMID- 11588221
TI  - Archaeology and Australian megafauna.

PMID- 11588222
TI  - Frontiers of aging.

PMID- 11588223
TI  - Infectious diseases. Rapid response could have curbed foot-and-mouth epidemic.

PMID- 11588224
TI  - Planetary science. Close look at the heart of Borrelly.

PMID- 11588225
TI  - Bioinformatics. Petition seeks public sharing of code.

PMID- 11588226
TI  - Psychopharmacology. Drug critic sues after school pulls job offer.

PMID- 11588227
TI  - Genetics. Closing in on the centromere.

PMID- 11588228
TI  - Cave art. Stone Age artists--or art lovers--unmasked?

PMID- 11588229
TI  - Science policy. New regulatory czar takes charge.

PMID- 11588230
TI  - Genetics. First gene linked to speech identified.

PMID- 11588231
TI  - Polar research. Fire guts British Antarctic lab.

PMID- 11588232
TI  - Genome research. Possible new heart disease risk factor.

PMID- 11588233
TI  - Development. New hints into the biological basis of autism.

PMID- 11588234
TI  - Development. Scant evidence for an epidemic of autism.

PMID- 11588235
TI  - Development. Desperate parents spark search for new treatment.

PMID- 11588236
TI  - Meteoritical Society. Ancient sky rocks and an unblemished Eros.

PMID- 11588237
TI  - Hungary. Money and political muscle help scientist turn the tide.

PMID- 11588238
TI  - Paleontology. Utah's fossil trove beckons, and tests, researchers.

PMID- 11588239
TI  - Essays on science and society. Is a new eugenics afoot?

PMID- 11588240
TI  - Cell cycle. Order from destruction.

PMID- 11588241
TI  - Surface science. How minerals react with water.

PMID- 11588242
TI  - Protein synthesis. Discriminating right from wrong.

PMID- 11588243
TI  - Planetary science. Jupiter and its moons.

PMID- 11588244
TI  - Unlocking the genome.

PMID- 11588245
TI  - So many choices, so little money.

PMID- 11588246
TI  - Japan and China gear up for 'postgenome' research.

PMID- 11588247
TI  - Evolving genomic metaphors: a new look at the language of DNA.
AB  - Recent genome-sequencing efforts have confirmed that traditional "good-citizen"
      genes (those that encode functional RNA and protein molecules of obvious benefit
      to the organism) constitute only a small fraction of the genomic populace in
      humans and other multicellular creatures. The rest of the DNA sequence includes
      an astonishing collection of noncoding regions, regulatory modules, deadbeat
      pseudogenes, legions of repetitive elements, and hosts of oft-shifty, self
      interested nomads, renegades, and immigrants. To help visualize functional
      operations in such intracellular genomic societies and to better encapsulate the
      evolutionary origins of complex genomes, new and evocative metaphors may be both
      entertaining and research-stimulating.

PMID- 11588248
TI  - Harnessing genomics and biotechnology to improve global health equity.
AB  - With decisive and timely action, genome-related biotechnology can be harnessed to
      improve global health equity. In June 2002 in Kananaskis, Canada, leaders of the
      G8 industrial nations will develop an action plan to support implementation of
      the New African Initiative. By extending their discussion of health issues raised
      in the New African Initiative to include genomics, G8 leaders could signal their
      intention to increase global health equity by preventing a health genomics divide
      from developing. There are already some early and growing examples of genome
      related biotechnology being applied successfully to health problems in developing
      countries. But how can genomics be systematically harnessed to benefit health in
      developing countries? We propose a five-point strategy, including research,
      capacity strengthening, consensus building, public engagement, and an investment
      fund.

PMID- 11588249
TI  - Global efforts in structural genomics.
AB  - A worldwide initiative in structural genomics aims to capitalize on the recent
      successes of the genome projects. Substantial new investments in structural
      genomics in the past 2 years indicate the high level of support for these
      international efforts. Already, enormous progress has been made on high
      throughput methodologies and technologies that will speed up macromolecular
      structure determinations. Recent international meetings have resulted in the
      formation of an International Structural Genomics Organization to formulate
      policy and foster cooperation between the public and private efforts.

PMID- 11588250
TI  - Protein structure prediction and structural genomics.
AB  - Genome sequencing projects are producing linear amino acid sequences, but full
      understanding of the biological role of these proteins will require knowledge of
      their structure and function. Although experimental structure determination
      methods are providing high-resolution structure information about a subset of the
      proteins, computational structure prediction methods will provide valuable
      information for the large fraction of sequences whose structures will not be
      determined experimentally. The first class of protein structure prediction
      methods, including threading and comparative modeling, rely on detectable
      similarity spanning most of the modeled sequence and at least one known
      structure. The second class of methods, de novo or ab initio methods, predict the
      structure from sequence alone, without relying on similarity at the fold level
      between the modeled sequence and any of the known structures. In this Viewpoint,
      we begin by describing the essential features of the methods, the accuracy of the
      models, and their application to the prediction and understanding of protein
      function, both for single proteins and on the scale of whole genomes. We then
      discuss the important role that protein structure prediction methods play in the
      growing worldwide effort in structural genomics.

PMID- 11588251
TI  - Making sense of eukaryotic DNA replication origins.
AB  - DNA replication is the process by which cells make one complete copy of their
      genetic information before cell division. In bacteria, readily identifiable DNA
      sequences constitute the start sites or origins of DNA replication. In
      eukaryotes, replication origins have been difficult to identify. In some systems,
      any DNA sequence can promote replication, but other systems require specific DNA
      sequences. Despite these disparities, the proteins that regulate replication are
      highly conserved from yeast to humans. The resolution may lie in a current model
      for once-per-cell-cycle regulation of eukaryotic replication that does not
      require defined origin sequences. This model implies that the specification of
      precise origins is a response to selective pressures that transcend those of once
      per-cell-cycle replication, such as the coordination of replication with other
      chromosomal functions. Viewed in this context, the locations of origins may be an
      integral part of the functional organization of eukaryotic chromosomes.

PMID- 11588252
TI  - Genomic and genetic definition of a functional human centromere.
AB  - The definition of centromeres of human chromosomes requires a complete genomic
      understanding of these regions. Toward this end, we report integration of
      physical mapping, genetic, and functional approaches, together with sequencing of
      selected regions, to define the centromere of the human X chromosome and to
      explore the evolution of sequences responsible for chromosome segregation. The
      transitional region between expressed sequences on the short arm of the X and the
      chromosome-specific alpha satellite array DXZ1 spans about 450 kilobases and is
      satellite-rich. At the junction between this satellite region and canonical DXZ1
      repeats, diverged repeat units provide direct evidence of unequal crossover as
      the homogenizing force of these arrays. Results from deletion analysis of
      mitotically stable chromosome rearrangements and from a human artificial
      chromosome assay demonstrate that DXZ1 DNA is sufficient for centromere function.
      Evolutionary studies indicate that, while alpha satellite DNA present throughout
      the pericentromeric region of the X chromosome appears to be a descendant of an
      ancestral primate centromere, the current functional centromere based on DXZ1
      sequences is the product of the much more recent concerted evolution of this
      satellite DNA.

PMID- 11588253
TI  - Replication dynamics of the yeast genome.
AB  - Oligonucleotide microarrays were used to map the detailed topography of
      chromosome replication in the budding yeast Saccharomyces cerevisiae. The times
      of replication of thousands of sites across the genome were determined by
      hybridizing replicated and unreplicated DNAs, isolated at different times in S
      phase, to the microarrays. Origin activations take place continuously throughout
      S phase but with most firings near mid-S phase. Rates of replication fork
      movement vary greatly from region to region in the genome. The two ends of each
      of the 16 chromosomes are highly correlated in their times of replication. This
      microarray approach is readily applicable to other organisms, including humans.

PMID- 11588254
TI  - A cosmic double helix in the archetypical quasar 3C273.
AB  - Finding direct evidence for plasma instability in extragalactic jets is crucial
      for understanding the nature of relativistic outflows from active galactic
      nuclei. Our radio interferometric observations of the quasar 3C273 made with the
      orbiting radio telescope, HALCA, and an array of ground telescopes have yielded
      an image in which the emission across the jet is resolved, revealing two
      threadlike patterns that form a double helix inside the jet. This double helical
      structure is consistent with a Kelvin-Helmholtz instability, and at least five
      different instability modes can be identified and modeled by a light jet with a
      Lorentz factor of 2 and Mach number of 3.5. The model reproduces in detail the
      internal structure of the jet on scales of up to 30 milli-arc seconds (
      approximately 300 parsecs) and is consistent with the general morphology of the
      jet on scales of up to 1 kiloparsec.

PMID- 11588255
TI  - Ferromagnetic imprinting of nuclear spins in semiconductors.
AB  - We examine how a ferromagnetic layer affects the coherent electron spin dynamics
      in a neighboring gallium arsenide semiconductor. Ultrafast optical pump-probe
      measurements reveal that the spin dynamics are unexpectedly dominated by
      hyperpolarized nuclear spins that align along the ferromagnet's magnetization. We
      find evidence that photoexcited carriers acquire spin-polarization from the
      ferromagnet, and dynamically polarize these nuclear spins. The resulting
      hyperfine fields are as high as 9000 gauss in small external fields (less than
      1000 gauss), enabling ferromagnetic control of local electron spin coherence.

PMID- 11588256
TI  - Spatiotemporal addressing of surface activity.
AB  - We have modified surface catalytic activity in real time and space by focusing an
      addressable laser beam to differentially heat a platinum (110) single-crystal
      surface. Ellipsomicroscopy imaging of local conditions (such as reactant and
      product local coverages) enabled us to close the loop between sensing and
      actuation (both spatiotemporally resolved). Pulses and fronts, the basic building
      blocks of patterns, could be formed, accelerated, modified, guided, and destroyed
      at will. Real-time image processing and feedback allow the design and
      implementation of new classes of nonlocal evolution rules.

PMID- 11588257
TI  - Submicrometer metallic barcodes.
AB  - We synthesized multimetal microrods intrinsically encoded with submicrometer
      stripes. Complex striping patterns are readily prepared by sequential
      electrochemical deposition of metal ions into templates with uniformly sized
      pores. The differential reflectivity of adjacent stripes enables identification
      of the striping patterns by conventional light microscopy. This readout mechanism
      does not interfere with the use of fluorescence for detection of analytes bound
      to particles by affinity capture, as demonstrated by DNA and protein bioassays.

PMID- 11588258
TI  - Organic carbon composition of marine sediments: effect of oxygen exposure on oil
      generation potential.
AB  - Anaerobic sedimentary conditions have traditionally been linked to the generation
      of the source rocks for petroleum formation. However, the influence of
      sedimentary redox conditions on the composition of freshly deposited organic
      matter (OM) is not clear. We assessed the effect of in situ exposure time to oxic
      conditions on the composition of OM accumulating in different coastal and deep
      sea sediments using solid-state 13C nuclear magnetic resonance (NMR). 13C NMR
      spectra were resolved into mixtures of model components to distinguish between
      alkyl carbon present in protein and nonprotein structures. There is an inverse
      relation between the length of exposure to oxic conditions and the relative
      abundance of nonprotein alkyl (alkylNP) carbon, whose concentration is two orders
      of magnitude higher in coastal sediments with short exposure times than in deep
      sea sediments with long exposure times. All alkylNP-rich samples contain a
      physically separate polymethylene component similar in composition to algaenans
      and kerogens in type I oil shales. The duration of exposure to oxic conditions
      appears to directly influence the quality and oil generation potential of OM in
      marine shales.

PMID- 11588259
TI  - Late Holocene climate and cultural changes in the southwestern United States.
AB  - Columnar stalagmites in caves of the Guadalupe Mountains during the late Holocene
      record a 4000-year annually resolved climate history for the southwestern United
      States. Annual banding, hiatuses, and high-precision uranium-series dating show a
      present day-like climate from 4000 to 3000 years ago, following a drier middle
      Holocene. A distinctly wetter and cooler period from 3000 to 800 years ago was
      followed by a period of present day-like conditions, with the exception of a
      slightly wetter interval from 440 to 290 years before the present. The stalagmite
      record correlates well with the archaeological record of changes in cultural
      activities of indigenous people. Such climate change may help to explain evidence
      of dwelling abandonment and population redistribution.

PMID- 11588260
TI  - Constraint to adaptive evolution in response to global warming.
AB  - We characterized the genetic architecture of three populations of a native North
      American prairie plant in field conditions that simulate the warmer and more arid
      climates predicted by global climate models. Despite genetic variance for traits
      under selection, among-trait genetic correlations that are antagonistic to the
      direction of selection limit adaptive evolution within these populations.
      Predicted rates of evolutionary response are much slower than the predicted rate
      of climate change.

PMID- 11588261
TI  - Conversion of a peroxiredoxin into a disulfide reductase by a triplet repeat
      expansion.
AB  - Pathways for the reduction of protein disulfide bonds are found in all organisms
      and are required for the reductive recycling of certain enzymes including the
      essential protein ribonucleotide reductase. An Escherichia coli strain that lacks
      both thioredoxin reductase and glutathione reductase grows extremely poorly.
      Here, we show that a mutation occurring at high frequencies in the gene ahpC,
      encoding a peroxiredoxin, restores normal growth to this strain. This mutation is
      the result of a reversible expansion of a triplet nucleotide repeat sequence,
      leading to the addition of one amino acid that converts the AhpC protein from a
      peroxidase to a disulfide reductase. The ready mutational interconversion between
      the two activities could provide an evolutionary advantage to E. coli.

PMID- 11588262
TI  - Success and virulence in Toxoplasma as the result of sexual recombination between
      two distinct ancestries.
AB  - Toxoplasma gondii is a common human pathogen causing serious, even fatal, disease
      in the developing fetus and in immunocompromised patients. Despite its ability to
      reproduce sexually and its broad geographic and host range, Toxoplasma has a
      clonal population structure comprised principally of three lines. We have
      analyzed 15 polymorphic loci in the archetypal type I, II, and III strains and
      found that polymorphism was limited to, at most, two rather than three allelic
      classes and no polymorphism was detected between alleles in strains of a given
      type. Multilocus analysis of 10 nonarchetypal isolates likewise clustered the
      vast majority of alleles into the same two distinct ancestries. These data
      strongly suggest that the currently predominant genotypes exist as a pandemic
      outbreak from a genetic mixing of two discrete ancestral lines. To determine if
      such mixing could lead to the extreme virulence observed for some strains, we
      examined the F(1) progeny of a cross between a type II and III strain, both of
      which are relatively avirulent in mice. Among the progeny were recombinants that
      were at least 3 logs more virulent than either parent. Thus, sexual
      recombination, by combining polymorphisms in two distinct and competing clonal
      lines, can be a powerful force driving the natural evolution of virulence in this
      highly successful pathogen.

PMID- 11588263
TI  - Uniform binding of aminoacyl-tRNAs to elongation factor Tu by thermodynamic
      compensation.
AB  - Elongation factor Tu (EF-Tu) binds all elongator aminoacyl-transfer RNAs (aa
      tRNAs) for delivery to the ribosome during protein synthesis. Here, we show that
      EF-Tu binds misacylated tRNAs over a much wider range of affinities than it binds
      the corresponding correctly acylated tRNAs, suggesting that the protein exhibits
      considerable specificity for both the amino acid side chain and the tRNA body.
      The thermodynamic contributions of the amino acid and the tRNA body to the
      overall binding affinity are independent of each other and compensate for one
      another when the tRNAs are correctly acylated. Because certain misacylated tRNAs
      bind EF-Tu significantly more strongly or weakly than cognate aa-tRNAs, EF-Tu may
      contribute to translational accuracy.

PMID- 11588265
TI  - Choosing and using services for sexual health: women's views.

PMID- 11588264
TI  - An apolipoprotein influencing triglycerides in humans and mice revealed by
      comparative sequencing.
AB  - Comparison of genomic DNA sequences from human and mouse revealed a new
      apolipoprotein (APO) gene (APOAV) located proximal to the well-characterized
      APOAI/CIII/AIV gene cluster on human 11q23. Mice expressing a human APOAV
      transgene showed a decrease in plasma triglyceride concentrations to one-third of
      those in control mice; conversely, knockout mice lacking Apoav had four times as
      much plasma triglycerides as controls. In humans, single nucleotide polymorphisms
      (SNPs) across the APOAV locus were found to be significantly associated with
      plasma triglyceride levels in two independent studies. These findings indicate
      that APOAV is an important determinant of plasma triglyceride levels, a major
      risk factor for coronary artery disease.

PMID- 11588266
TI  - Destigmatising STIs: remaining challenges, new opportunities.

PMID- 11588267
TI  - Oral sex and HIV transmission.

PMID- 11588268
TI  - Resurgence of syphilis in England: time for more radical and nationally
      coordinated approaches.

PMID- 11588269
TI  - An outbreak of early syphilis: cases from North Manchester General Hospital.
AB  - OBJECTIVES: To describe the features of an outbreak of early syphilis in North
      Manchester. METHODS: Retrospective KC60 and case note review. RESULTS: In a 25
      month period, 10 cases of primary, 22 of secondary, and nine cases of early
      latent syphilis were diagnosed. 39 were homosexual or bisexual men, 20 being co
      infected with HIV. Most infections were acquired locally and in 19/41 cases oral
      sex was the only risk factor. High rates of unprotected anal sex were reported
      among the homosexual men and co-infection with other STIs was common. CONCLUSION:
      This outbreak will facilitate the spread of HIV in the homosexual male
      population. Unsafe sexual practice is common and the perception that oral sex is
      "safe" needs revisiting. Delays in accessing GUM clinic appointments must be
      addressed as part of the control strategy.

PMID- 11588270
TI  - Syphilis in the fens.

PMID- 11588271
TI  - The great pretender returns to Dublin, Ireland.
AB  - BACKGROUND: An outbreak of syphilis has been identified primarily in Dublin,
      Ireland. On a background of a stable low incidence of syphilis, a significant
      increase in the number of cases of syphilis has been observed over the past 18
      months. RESULTS: 181 cases of syphilis were seen in this period. 121 were defined
      as early syphilis. These cases were mainly among men who have sex with men (92%).
      A high rate of HIV co-infection was present; 16 patients who regularly attended
      HIV clinics were diagnosed with early syphilis. Nine patients were co-diagnosed
      with HIV and early syphilis. High risk behaviour and concurrent diagnoses with
      other sexually transmitted infections were prevalent in this cohort. Sexual
      networks were also investigated. CONCLUSION: An education campaign, widespread
      advertisements, and on-site testing in commercial venues have revealed further
      cases. Safer sex messages need to be emphasised particularly among the HIV
      population. Further innovative strategies continue to be explored.

PMID- 11588272
TI  - Surfing with spirochaetes: an ongoing syphilis outbreak in Brighton.
AB  - BACKGROUND/OBJECTIVES: There has been a recent shift in the epidemiology of early
      syphilis in the developed world with sporadic outbreaks on a historic low level
      of background disease. Here we describe an ongoing outbreak of syphilis in
      Brighton. METHODS: Data collected on all patients with a diagnosis of early
      infectious syphilis at Brighton GUM clinic. RESULTS: 30 cases of early syphilis
      were diagnosed over a 25 month period beginning in July 1999. 28 were homosexual
      or bisexual men, giving a rate of 134 cases per 100 000 homosexual men. The cases
      reported a median of three sexual contacts (range 1-50) in the preceding 6 months
      and 77% had concurrent regular and casual partners. 83% of contacts were casual
      and untraceable. Over one third (11) of these cases reported oral sex as their
      only risk factor for syphilis acquisition and were unaware of this transmission
      route. 70% were diagnosed with primary or secondary infection, the remaining 30%
      being asymptomatic with early latent infection. Eight of the cases were HIV
      positive and a further eight remain untested for HIV. At least one concurrent STI
      was found in 40% of cases. Regular outbreak control meetings, involving relevant
      healthcare professionals, were held to plan appropriate interventions.
      CONCLUSION: The high rate of casual and untraceable contacts in this outbreak
      suggest that alternative control measures are necessary, including on-site
      testing and further health education regarding the oral transmission of syphilis.
      Continued vigilance for syphilis is essential, especially in those patients who
      are HIV positive.

PMID- 11588273
TI  - "The syphilis enigma": the riddle resolved?

PMID- 11588274
TI  - Homosexual men, HIV, and sexual risk in 2001.

PMID- 11588275
TI  - Syphilis: mimicking yet another disease!

PMID- 11588276
TI  - Anal intraepithelial neoplasia in HIV positive people.
AB  - OBJECTIVE: To review the current literature on HIV associated anal
      intraepithelial neoplasia (AIN). METHODS: A comprehensive Medline/Pubmed search
      was performed for the years 1980-2001 (January) for articles pertaining to HIV
      associated anal intraepithelial neoplasia. From the MeSH terms "anal
      intraepithelial neoplasia" and "anal cancer" the following subheadings were used:
      HIV, homosexual men, HPV, Epidemiology, Etiology, Mortality, Diagnosis,
      Screening, Drug Therapy, Surgical Therapy, Radio Therapy, Risk factors, ASIL. The
      search was limited to "human" for all searches. In the absence of enough
      "randomised controlled trials" the search was extended to clinical trials,
      reviews, and case reports. One analysis on cost effectiveness and two abstracts
      presented at 12th World AIDS Conference and 6th Conference on Retrovirus and
      Opportunistic Infections were included. The 44 publications referred to originate
      from the United Kingdom (9), the United States (26), and Denmark (5), with one
      each from Switzerland, Germany, Australia, and France. The Cochrane Database of
      systematic reviews yielded 11 complete reviews for "anal cancer" and none for
      "anal intraepithelial neoplasia." The textbook of AIDS-related cancers and their
      treatment was consulted. We also included our personal experience from the
      treatment of patients at the Chelsea and Westminster Hospital, one of the largest
      centres for the management of HIV disease in Europe. CONCLUSION: Routine anal
      cytological screening followed by appropriate management of AIN is an important
      issue for HIV infected patients. The natural history of AIN has not been fully
      established and this prevents clinicians from defining clear management
      protocols. There is early evidence that the benefits of highly active
      antiretroviral therapy (HAART) in terms of restoring immune function and reducing
      opportunistic infections and some neoplasms may not extend to regression of AIN.
      Under these circumstances it might be predicted that AIN and subsequent
      progression to invasive anal cancer would rise as HAART prolongs the lives of
      seropositive people. However, routine anal cytological screening will surely have
      to await an effective proved intervention for AIN and this would seem to be a
      pressing clinical goal.

PMID- 11588277
TI  - Study size.

PMID- 11588278
TI  - Choosing and using services for sexual health: a qualitative study of women's
      views.
AB  - OBJECTIVE: To explore women's accounts of choosing and using specialist services
      for sexual health. METHODS: A qualitative study involving semistructured
      interviews with 37 women screened for Chlamydia trachomatis attending
      genitourinary medicine and family planning clinics in an East Midlands health
      authority. RESULTS: In making the decision to seek help, women act on a range of
      specific prompts, including lay ideas about the significance of symptoms; their
      own behaviour; their partner's symptoms or behaviour; contact tracing; and health
      promotion. Some women do not seek help specifically in relation to sexual health
      but are identified as being at risk of sexually transmitted infections (STIs)
      during routine consultations. Important influences on women's choice of services
      include the lay referral system, "insider" knowledge of health services, referral
      by health professionals, and need to have alternatives to general practice care.
      Women's willingness to access services is mediated by psychosocial factors such
      as embarrassment. They may use smear tests as a legitimate opportunity to raise
      questions about sexual health. Women's priorities for services are that their
      feelings of stigma and embarrassment are managed appropriately; that staff
      communicate well and are sensitive to their emotions and comfort during tests and
      procedures; that they are "in control" when obtaining test results; and that
      confidentiality is preserved. CONCLUSIONS: A detailed understanding of both lay
      people's response to symptoms or behaviour that indicates risk of an STI and
      their needs when using services should inform interventions aimed at encouraging
      secondary prevention of STIs.

PMID- 11588279
TI  - "That sort of place...where filthy men go...": a qualitative study of women's
      perceptions of genitourinary medicine services.
AB  - BACKGROUND: A stigma is a pejorative social label. Stigmatisation is a process by
      which individuals are made to experience isolation and reduced opportunities in
      life. Some diseases are particularly associated with stigmatising attitudes; this
      applies particularly to sexually transmitted infections. Although several studies
      report the effects of stigma, no study to date has attempted to investigate its
      nature, which is a prerequisite to designing health interventions. METHODS: This
      qualitative, exploratory study investigated the experience of stigma among young
      women recently diagnosed with an STI and considered the implications of these
      experiences in terms of maximising access to GUM clinics. RESULTS: Three themes
      were identified from interviews undertaken with women recruited in family
      planning and genitourinary medicine (GUM) clinics: the perception of STIs as a
      condition of "others," the threatening nature of the GUM clinic, and the
      evolution of the experience of stigma within the GUM clinic. CONCLUSION: More
      open discussion and education about sexual health services and STIs should take
      place at a general population level; awareness of sexual health services should
      be raised in inclusive ways, which are seen as relevant to the needs of a wide
      range of individuals; medical, nursing, and counselling staff in GUM clinics
      should be supported in their efforts to reduce the experience of stigma. Finally,
      future interventions designed to improve access to sexual health services should
      formally assess their impact on stigma.

PMID- 11588280
TI  - Prevalence of infectious diseases in Bangladeshi women living adjacent to a truck
      stand: HIV/STD/hepatitis/genital tract infections.
AB  - BACKGROUND: Little is known about infection rates for human immunodeficiency
      virus (HIV) and other diseases that can be transmitted sexually in Bangladeshi
      women who may be at intermediate levels of risk--that is, women who are not
      commercial sex workers (CSWs) but whose sexual contacts may include men at high
      risk for STD. This study examines HIV/hepatitis/STD and other genital tract
      infections in women living near Tejgaon truck stand in Dhaka, Bangladesh.
      METHODS: This population based study was conducted from January to December 1998.
      A random sample of 384 women provided urine and blood samples and participated in
      an interview; 261 of them also had a physical examination in which vaginal and
      cervical specimens were taken. Laboratory tests included PCR on urine and
      cervical swabs for gonorrhoea and chlamydia, culture for trichomoniasis, serology
      tests for syphilis, herpes simplex 2, hepatitis B, C, D, HIV1, HIV2, and clinical
      diagnoses of other genital tract infections. RESULTS: None of the participants
      tested positive for HIV. In the 261 women who had a physical examination,
      trichomoniasis was detected in 19.5%, chlamydia in 3.4%, gonorrhoea in 5.4%,
      bacterial vaginosis in 37.2%, and candidiasis in 10%. In the full sample of 384
      women, with tests of urine and blood, prevalence of infection with chlamydia,
      gonorrhoea, syphilis, and herpes simplex 2 was detected in 0%, 6.3%, 5.7%, and
      32% respectively. Almost 50% of the subjects had ever been exposed to hepatitis
      B, 3.6% were currently infective, 1.6% had hepatitis C, and none had hepatitis D.
      CONCLUSION: The high prevalence of certain of these infectious diseases indicates
      the need to implement prevention interventions with these women and, perhaps more
      importantly, with their male partners. Qualitative research is needed to provide
      insights into their sexual behaviour and the contexts in which high risk
      behaviours occur.

PMID- 11588281
TI  - Where do sex workers go for health care? A community based study in Abidjan, Cote
      d'Ivoire.
AB  - OBJECTIVES: To describe health seeking behaviour of female sex workers in
      Abidjan, Cote d'Ivoire. METHODS: A population based survey among a representative
      sample of 500 female sex workers and six focus group discussions. RESULTS: The
      sites of first encounter for care for the last STI episode included a public
      hospital or health centre (28%), a private clinic (16%), a confidential clinic
      (13%), a pharmacy (13%), and the informal sector (23%). The agreement between
      preferred and actual services used was weak (kappa 0.16). CONCLUSIONS: Sex
      workers expressed interest in seeking STI care in a wide range of public and
      private healthcare facilities. Those services should be upgraded to better
      respond to their sexual health needs.

PMID- 11588282
TI  - Rising incidence and prevalence of herpes simplex type 2 infection in a cohort of
      26 year old New Zealanders.
AB  - OBJECTIVES: To examine changes in the incidence and prevalence of herpes simplex
      type 2 (HSV-2) infection in a birth cohort of 26 year old New Zealanders in whom
      seroprevalence had been measured at 3.4% at age 21. METHODS: Sera from 869 cohort
      members were tested using an indirect IgG enzyme linked immunoassay specific to
      the HSV-2 glycoprotein G. Serological results were compared with detailed sexual
      histories. RESULTS: In all, 96 participants (11%) were seropositive for HSV-2,
      including at least 56 who seroconverted after their 21st birthday. Among those
      known to be seronegative at age 21, the annual seroconversion rate was 13.5 cases
      per 1000 per year, compared with 8.1 cases per 1000 per sexually active year
      before age 21. New infections were associated with female sex and an early age of
      first intercourse. The average rate of partner change was lower in the cohort
      after age 21, and was only modestly increased among those who acquired new HSV-2
      infections between ages 21 and 26. CONCLUSIONS: HSV-2 seroprevalence has risen
      sharply in this sexually active cohort, despite a reduction in the overall level
      of partner change. Increased rates of HSV-2 acquisition after age 21 may be due
      to a higher prevalence of infection in the pool of potential partners encountered
      during the third decade of life. Factors related to partner choice may have more
      influence on the risk of HSV-2 infection than the number of sexual partners
      alone.

PMID- 11588283
TI  - Prevalence of herpes simplex type 2 and syphilis serology among young adults in a
      rural Gambian community.
AB  - OBJECTIVES: To estimate prevalence and risk factors for herpes simplex 2 (HSV2)
      positivity, syphilis and Chlamydia trachomatis infection among rural people aged
      15-34 in the Gambia. METHODS: Questionnaires and serum samples were collected
      from 1076 men and women aged 15-34 during a cross sectional prevalence survey in
      a rural area of the Gambia. Sera were screened for antibodies to herpes simplex
      virus type 2 (HSV2), and for syphilis using Treponema pallidum haemagglutination
      assay (TPHA) and rapid plasma reagin (RPR) tests. Urine was tested by polymerase
      chain reaction (PCR) for C trachomatis infection. RESULTS: 28% of women and 5% of
      men were HSV2 ELISA positive; 10% of women and 2% of men were TPHA positive; and
      7% of women and 1% of men were both RPR and TPHA positive. Out of 1030 urine
      sample tested only six were positive for C trachomatis. 7% of those who reported
      never having sex were positive for one or other of these tests. Prevalences of
      all STIs increased with age and were higher in women than men. Women were much
      less likely than men to seek treatment for STI symptoms at a health centre.
      Married people were at increased risk of an STI compared with single people. Jola
      and Fula women had a higher prevalence of HSV2 than women from other ethnic
      groups, and Fulas also had a higher prevalence of RPR/TPHA positivity. The
      limited number of sexual behaviour questions were not significantly associated
      with STIs after adjustment for age, marital status, and ethnic group.
      CONCLUSIONS: The prevalences of the ulcerative infections HSV2 and syphilis in
      this population are a cause for concern. In a setting where HIV1 prevalence
      remains low this indicates an urgent need for STI control and behaviour change
      programmes to prevent an HIV epidemic. Concerns about the validity of reported
      sexual behaviour data high light the necessity of biological markers in the
      evaluation of behaviour change programmes.

PMID- 11588284
TI  - Macrophages are increased in cervical epithelium of women with cervicitis.
AB  - BACKGROUND: Sexually transmitted diseases (STIs) are major causes of morbidity in
      women. The mechanisms involved in establishment of genital mucosal infection are
      poorly defined. OBJECTIVE: To investigate changes in cervical epithelial (CE)
      CD45+ cell subpopulations in women with microscopic evidence of cervicitis (n=9)
      and those without (n=12). METHODS: CE samples were obtained using cytobrush
      including matched venous blood. CE and peripheral blood (PB) mononuclear cells
      were analysed by flow cytometry for CD3+, CD4+, CD8+, CD14+,CD19+, and HLA-DR+
      expression. RESULTS: Women with cervicitis had increased CE macrophages compared
      with those without (p<0.05). MHC class II+ cells were predominant in all cervical
      samples. Considerably fewer B lymphocytes were found in cervical samples in both
      groups of women. No changes were observed in cervical T lymphocyte subsets.
      However, a relative CD8+ lymphocytosis in PB was noted in women with cervicitis.
      CONCLUSION: The increased numbers of CE macrophages in women with cervicitis may
      have important implications for pathogenesis of STIs including human
      immunodeficiency virus infection.

PMID- 11588285
TI  - Passion, stigma, and STI.

PMID- 11588286
TI  - A randomised controlled trial of the effectiveness of combining video role play
      with traditional methods of delivering undergraduate medical education.
AB  - OBJECTIVE: To determine the effectiveness of video role play with structured
      feedback in improving undergraduate communication skills and application of
      knowledge in genitourinary medicine. DESIGN: A blind, randomised, controlled
      trial. SUBJECTS AND SETTING: Fourth year undergraduates attending a 5 week
      attachment in genitourinary medicine during 1997 at a London medical school.
      INTERVENTION: A randomly selected sample group of undergraduates were filmed in
      the role of a doctor interviewing a patient (played by an actor) presenting with
      a genitourinary (GU) problem. Structured feedback by a GU physician and an
      educational psychologist was given a week later. The control group of
      undergraduates did not receive this training intervention. OUTCOME MEASURES:
      Student performance in two stations of an objective structured clinical
      examination (OSCE), administered at the end of their attachment. This tested
      communication skills and knowledge in GU settings. RESULTS: 132 undergraduates
      were assessed in the OSCE. 40 of these were in the sample group who received
      training using video role play with feedback and 92 were in the control group.
      The sample group scored significantly higher marks than the control group
      (p<0.001). CONCLUSIONS: Video role play with structured feedback is effective in
      improving undergraduate communication skills and application of knowledge in GU
      medicine settings.

PMID- 11588287
TI  - Hyperlactataemia and hepatic steatosis: mitochondrial toxicity of nucleoside
      reverse transcriptase inhibitors.

PMID- 11588288
TI  - Ejaculatory pain associated with a pelvic arteriovenous malformation.

PMID- 11588290
TI  - Trends of gonorrhoea and early syphilis in Belgrade, 1985-99.

PMID- 11588291
TI  - Study of risk factors associated with HIV seropositivity in STD patients at
      Mumbai, India.

PMID- 11588293
TI  - Dial 1097 (toll free).

PMID- 11588294
TI  - Rates of gonorrhoea and chlamydia in black ethnic groups.

PMID- 11588295
TI  - Is bacterial vaginosis a sexually transmitted infection.

PMID- 11588296
TI  - Substantial increase in gonorrhoea among homosexual men attending an STD centre
      in Toulouse, France.

PMID- 11588297
TI  - Human papillomavirus PCR direct sequencing study of cervical precancerous lesions
      in Quebec children.

PMID- 11588298
TI  - Adverse reaction to antimycobacterials administered as a combination tablet with
      no reaction to the same drugs in isolation.

PMID- 11588299
TI  - Genital piercing and sexually transmitted infections.

PMID- 11588301
TI  - Safer sex in HIV infected patients in London: practices and risks.

PMID- 11588300
TI  - Increasing HIV prevalence in STD clinic attendees in Delhi, India: 6 year (1995
      2000) hospital based study results.

PMID- 11588302
TI  - Stroke: 30 years of progress: 1987-1991.

PMID- 11588303
TI  - Decline in US stroke mortality: an analysis of temporal patterns by sex, race,
      and geographic region.
AB  - BACKGROUND AND PURPOSE: Although stroke mortality rates have declined rapidly
      over the past 30 years, the decline has slowed to a plateau. Here, we assess
      whether the race-sex-region groups have participated equally in this decline and
      whether there are groups in which stroke mortality rates are still declining, and
      we predict how these rates will eventually differ. METHODS: Data on stroke
      mortality in the United States between 1968 and 1996 were analyzed in a 3-step
      procedure: (1) we calculated "crude" age-adjusted stroke mortality rates by race,
      sex, and county; (2) we "smoothed" the rates across counties and years; and (3)
      we fit a model to describe the temporal pattern. From this model we calculated
      the percent decline in stroke mortality, the anticipated additional decline
      (thereby identifying regions that will continue to decline), and the anticipated
      eventual stroke mortality rates. RESULTS: Maps by race-sex-region group describe
      the above parameters. White men have experienced the largest decline in stroke
      mortality, and black men have seen the smallest. Generally, stroke mortality
      appears to still be slowly declining for blacks but not for whites. Geographic
      differences in stroke mortality are predicted to persist. CONCLUSIONS: The
      analysis suggests that the Deep South (Alabama and Mississippi) will fall from
      the stroke belt and be replaced by other regions (notably Oregon, Washington, and
      Arkansas). New York City and southern Florida had low stroke mortality rates in
      1968, have experienced large declines, and continue to experience declines,
      resulting in even larger relative heterogeneity of stroke mortality rates. The
      reasons for these differences in the pattern of the decline in stroke mortality
      are not understood.

PMID- 11588304
TI  - Trend of stroke hospitalization, United States, 1988-1997.
AB  - BACKGROUND AND PURPOSE: Age-adjusted stroke mortality in the United States has
      declined in recent decades. However, the course of stroke incidence is less
      certain. To address this issue, we determined trends of stroke hospitalization
      and in-hospital case fatality during 1988-1997. METHODS: Stroke hospitalization
      was estimated from National Hospital Discharge Survey as numerator and Current
      Population Survey as denominator. Hospitalization rates were determined and
      stratified by patient characteristics. Average length of hospital stay was also
      determined. In-hospital mortality was specified by sex, age, and other patient
      characteristics. The change in these rates over 10 years and average annual
      percent changes were calculated. RESULTS: During 1988-1997, age-adjusted stroke
      hospitalization rate increased 18.6% (from 560 to 664/100 000; P=0.043), while
      total hospitalization increased from 592 811 to 821 760. This increase was
      limited to persons aged >/=65 years. Patients in the South had the highest stroke
      hospitalization rates, and those in the West had the lowest. Overall, 58% of
      strokes were classified as ischemic, 13% as hemorrhagic, and 29% as other. Over
      these 10 years, stroke patients having coincident diabetes, hypertension, and
      congestive heart failure increased 17.4% (P=0.17), 34% (P=0.05), and 31%
      (P=0.091), respectively. The average length of hospital stay fell from 11.1 to
      6.2 days (44.1%; P=0.012). As a result, despite an increase in hospitalizations
      for stroke, the total person-days in hospital actually decreased by 22% (P=0.06).
      CONCLUSIONS: The declining age-adjusted stroke mortality in the United States has
      not been accompanied by a fall in hospitalization over recent years. Thus far,
      however, decrease in length of stay has more than offset increased admission. At
      the same time, the sharp drop in hospital case fatality rates suggests that
      continuing decline in stroke mortality may be due, in large part, to improved
      survival after acute stroke.

PMID- 11588305
TI  - A population study of stroke in West Ukraine: incidence, stroke services, and 30
      day case fatality.
AB  - BACKGROUND AND PURPOSE: According to World Health Organization statistics,
      Ukraine has extremely high stroke mortality. No population-based prospective
      studies of stroke incidence have been performed yet in this European country with
      approximately 50 million inhabitants. High reported rates of stroke mortality in
      official statistics conflict with some locally published incidence data in
      Ukraine. To obtain accurate data, we evaluated stroke incidence and 30-day case
      fatality in a prospective population study in the West Ukrainian city of Uzhgorod
      with a population of 126 000 inhabitants. METHODS: Case certification by
      neurologists and follow-up at 30 days after stroke for all patients identified by
      any level of the health service system were performed for a 12-month period.
      RESULTS: We identified 352 stroke cases. The age-standardized incidence was 341
      and 238 of 100 000 and mortality was 83 and 69 of 100 000 with the use of the
      European or world standard population for standardization. Mean age of stroke
      patients was 63.4+/-12.5 years. Rate of hospitalization was 66%. Hospitalized
      patients were >10 years younger than those treated in their homes. The 30-day
      case fatality rates were 15.4% among hospitalized patients and 36.8% among those
      treated at home. Overall 30-day case fatality was 23.3%. CONCLUSIONS: Stroke
      incidence and 30-day case fatality in this West Ukrainian city were similar to
      those of some West European countries and were much lower than what could be
      expected from World Health Organization statistics. The relatively low incidence
      rate seems accurate; because of the organization of local stroke services, it is
      not probable that a considerable proportion of patients with acute stroke could
      bypass all levels of the acute care health system. Local health statistics
      reported a much lower number of stroke cases and stroke deaths than found in our
      survey; thus, further study is needed to clarify the reason for the discrepancy
      between local data and the high reported stroke mortality in Ukraine.

PMID- 11588306
TI  - Validating the Questionnaire for Verifying Stroke-Free Status (QVSFS) by
      neurological history and examination.
AB  - BACKGROUND AND PURPOSE: The Questionnaire for Verifying Stroke-Free Status
      (QVSFS) is an 8-item structured interview designed to identify stroke-free
      individuals. Previously, the QVSFS was validated with medical record review in a
      cohort with a low prevalence (7.1%) of stroke or transient ischemic attack (TIA).
      The objective of this study was to evaluate the validity of the QVSFS by
      comparing it with stroke status as determined by neurological history and
      examination in a population with a higher prevalence of stroke. METHODS: A
      research assistant administered the QVSFS to outpatients from Veterans
      Administration stroke and general medicine clinics. Subjects were defined as
      QVSFS negative if responses to all 8 questions were negative. Questions requiring
      rephrasing or clarification were noted. Neurologists, blinded to QVSFS scores,
      interviewed and examined all subjects to determine stroke-free status, defined as
      no history or examination findings of previous stroke and/or TIA. RESULTS: One
      hundred fifty-five subjects were examined; mean age was 70 years; 98.1% were
      male. Seventy-eight subjects were determined to be stroke free by the
      neurologist. The negative predictive value of the QVSFS was 0.96, with positive
      predictive value of 0.71. No question required rephrasing or clarification >5
      times. Twenty-two subjects (14.2%) required rephrasing or clarification of at
      least 1 question. CONCLUSIONS: The QVSFS can effectively identify stroke-free
      individuals with a high degree of accuracy, even in a population with a large
      proportion of patients with prior stroke or TIA. Accuracy for identifying
      subjects with stroke and/or TIA is lower, but the QVSFS may still be useful as a
      screening tool in that regard.

PMID- 11588307
TI  - Longitudinal changes of metabolites in frontal lobes after hemorrhagic stroke of
      basal ganglia: a proton magnetic resonance spectroscopy study.
AB  - BACKGROUND AND PURPOSE: We investigated serial metabolic changes in frontal lobes
      of patients with deep intracerebral hemorrhage (ICH) to examine the correlation
      between N-acetylaspartate (NAA) and degree of motor impairment or clinical
      outcome. METHODS: - Twenty patients with deep ICH were examined with proton
      magnetic resonance spectroscopy with the application of a multivoxel method (1
      voxel=10x10x20 mm; 64 voxels). NAA/creatine ratios in the white matter of the
      primary motor and premotor areas on both sides were measured sequentially: within
      48 hours, at 2 weeks, and 1 month after onset. The National Institutes of Health
      Stroke Scale and Barthel Index for disability were measured for each patient.
      RESULTS: - In the primary motor area on the affected side, where the hematoma did
      not extend, the NAA/creatine ratio decreased sequentially. At 48 hours and 2
      weeks after onset, a negative correlation was detected between NAA/creatine and
      hematoma volume, but there was no correlation 1 month later. At 2 weeks,
      NAA/creatine correlated negatively with motor impairment (r=-0.750), and there
      was a significant correlation with clinical outcome as early as 2 weeks after
      onset (r=0.954). These sequential changes of NAA/creatine varied according to
      patients' long-term clinical outcome. Patients with poor outcome demonstrated
      notable reduction of NAA/creatine over the bilateral frontal lobes. CONCLUSIONS: 
      The delayed gradual reduction of NAA/creatine ratio in the frontal lobes
      correlates with motor deficit and clinical outcome after deep ICH, suggesting
      that the neural networks in the frontal lobe could be important for recovery.

PMID- 11588308
TI  - Evaluation of risk factors for stroke/embolism and of complications due to
      anticoagulant therapy in atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: We sought to assess in outpatients with atrial
      fibrillation and oral anticoagulation (1) whether the complication rate is
      influenced by the presence of the risk factors age >65 years, arterial
      hypertension, diabetes, or previous stroke; (2) whether the complication rate is
      influenced by the number of additional drugs taken by patients; and (3) whether
      problems and interventions differ between patients with or without complications.
      METHODS: - Clinical characteristics, drugs, problems, interventions, and
      complications were registered during 2 years. RESULTS: - Three hundred sixty
      patients (mean age, 68 years; 43% female) were observed for 383 patient-years.
      Patients aged >65 years had more serious, life-threatening, or fatal
      complications (11% versus 5.3%/100 patient-years; P=0.0428) than younger
      patients. Patients with diabetes had more life-threatening and fatal
      complications (2.8% versus 0.6%/100 patient-years; P=0.0354) than patients
      without. The complication rate did not differ regarding the presence of previous
      stroke or hypertension. Patients who took </=3 drugs had fewer complications than
      patients who took more (4.3% versus 24.4%/100 patient-years; P=0.0041). Patients
      with complications complained more of chest (48% versus 28%/100 patient-years;
      P=0.0113) and abdominal pain (30% versus 13%/100 patient-years; P=0.0057), more
      frequently failed to keep appointments (134% versus 107%/100 patient-years;
      P=0.0321), had a higher tracking rate (134% versus 105%/100 patient-years;
      P=0.0272), and took more additional drugs (4.6 versus 3.5 drugs per day;
      P=0.0063) than patients with no complications. CONCLUSIONS: - Patients with
      increased age or diabetes mellitus or those who take >3 drugs per day have an
      increased complication rate and thus need especially careful monitoring of oral
      anticoagulation, including adequate pain control.

PMID- 11588309
TI  - Association between infection with Helicobacter pylori and Chlamydia pneumoniae
      and risk of ischemic stroke subtypes: Results from a population-based case
      control study.
AB  - BACKGROUND AND PURPOSE: Helicobacter pylori and Chlamydia pneumoniae have been
      associated epidemiologically and pathogenetically with coronary atherosclerosis.
      However, population-based data on chronic infection and stroke are lacking.
      Therefore, we investigated the association of both bacterial pathogens and
      ischemic stroke subtypes in a population-based case-control study. METHODS:
      Patients with first ischemic stroke in the population-based Erlangen Stroke
      Project were collected as cases. Neighborhood controls were drawn from the study
      population, matched for age, sex, and place of residence. IgG antibodies to H
      pylori were measured by enzyme immunoassay, and IgG antibodies to C pneumoniae
      were measured by microimmunofluorescence technique. Conditional logistic
      regression was used. Analyses were stratified for etiologic stroke subtypes
      according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria.
      RESULTS: A total of 145 case and 260 control subjects were included. Chronic H
      pylori infection was associated with a higher risk of stroke caused by small
      artery occlusion (adjusted odds ratio, 3.31; 95% CI, 1.15 to 9.56) and a lower
      risk of cardioembolic stroke (adjusted odds ratio, 0.21; 95% CI, 0.06 to 0.71).
      Overall, elevated H pylori as well as elevated C pneumoniae antibodies were not
      associated with ischemic stroke. CONCLUSIONS: Our population-based study does not
      provide evidence of any strong association between the immune response to C
      pneumoniae as a marker of prior infection and ischemic stroke. Further studies
      are required to reveal the role of chronic H pylori infection as an independent
      risk factor for the subgroup small-artery occlusion.

PMID- 11588310
TI  - Parity and carotid artery atherosclerosis in elderly women: The Rotterdam Study.
AB  - BACKGROUND AND PURPOSE: It has been postulated that physiological changes in the
      cardiovascular system, lipids, and glucose metabolism during pregnancy may
      increase subsequent risk of cardiovascular disease. Examination of the
      association between parity and risk factors for atherosclerosis may contribute
      information regarding possible mechanisms. METHODS: The relationship of parity
      with cardiovascular risk factors and the presence of carotid atherosclerosis was
      examined in the Rotterdam Study, a population-based study comprising 4878 women
      aged 55 years and older. Carotid atherosclerosis was assessed by ultrasonographic
      detection of plaques in the common carotid artery and bifurcation. Logistic
      regression models were used to compute odds ratios and 95% confidence intervals,
      adjusted for confounding factors. RESULTS: Parity was inversely associated with
      high-density lipoprotein cholesterol, and alcohol intake. Parity was positively
      associated with body mass index, total/HDL cholesterol ratio, insulin resistance,
      age at menopause, and socioeconomic status. Relative to nulliparous women, parous
      women had 36% (9% to 71%) greater risk of carotid atherosclerosis, rising to 64%
      in women with >/=4 children (19% to 127%). Adjustment for known cardiovascular
      risk factors, including insulin resistance and current lipid levels, did not
      diminish the magnitude of this association. CONCLUSIONS: Data demonstrated that
      there is a positive association between parity and risk of carotid artery plaques
      in elderly women and, further, that high parity is associated with lower HDL
      cholesterol levels and higher glucose/insulin ratios long after childbearing has
      ceased.

PMID- 11588311
TI  - Hypertension status is the major determinant of carotid atherosclerosis: a
      community-based study in Taiwan.
AB  - BACKGROUND AND PURPOSE: Extracranial carotid artery (ECCA) atherosclerosis has
      been associated with hypertension-related stroke. The present study was aimed at
      investigating the determinants of ECCA atherosclerosis in patients with
      hypertension in Taiwan. METHODS: The extent and severity of ECCA atherosclerosis
      were measured by high-resolution B-mode ultrasonography and expressed as maximal
      intima-media thickness (IMT) of the common carotid artery, ECCA plaque score, and
      carotid stenosis >/=50%. From July through December 1996, 263 hypertensive
      patients (146 with hypertension and 117 with borderline hypertension) and 270
      normotensive adults from the Chin-Shan Community Cardiovascular Cohort
      participated in this study. Risk factors and ECCA atherosclerosis were stratified
      by the blood pressure status. RESULTS: A significant dose-response relationship
      was found between the status of hypertension and the severity of carotid
      atherosclerosis. Multivariate logistic regression models revealed that
      hypertension (including borderline), male gender, smoking, and age >/=65 years
      significantly increased the risk of thicker IMT. The risk of ECCA plaque score >6
      increased significantly in conjunction with hypertension, age >/=65 years, left
      ventricular hypertrophy on ECG, and smoking. However, hypertension and smoking
      were the 2 evident determinants of carotid stenosis >/=50% after adjustment for
      other covariates. Compared with the normotensive subjects, the ORs (and 95% CIs)
      for the hypertensive patients to develop carotid atherosclerosis were 5.0 (3.0 to
      8.4) indexed by maximal common carotid artery IMT >/=75th percentile, 3.7 (1.8 to
      7.9) by ECCA score >6, and 4.8 (1.4 to 16.5) by carotid stenosis >/=50%.
      CONCLUSIONS: Hypertension strongly influence carotid atherosclerosis. Our
      findings reinforce the hypothesis that hypertension has a major role in the
      pathogenesis of atherosclerosis.

PMID- 11588312
TI  - Deep cerebral infarcts extending to the subinsular region.
AB  - BACKGROUND AND PURPOSE: We sought to determine the clinical and radiological
      features and pathogenesis of deep cerebral infarcts extending to the subinsular
      region (DCIs). METHODS: - We defined DCIs as subcortical infarcts extending
      between the lateral ventricle and the subinsular region with a paraventricular
      extent >1.5 cm and a subinsular extent of at least one third of the
      anteroposterior extent of the insula. We identified patients by review of imaging
      records and noted the clinical information, risk factors, and investigations. We
      compared risk factors and clinical features between DCIs and "internal border
      zone" infarcts restricted to the paraventricular region. RESULTS: - Eight
      patients were studied. The typical clinical features of DCIs were hemiparesis,
      aphasia, dysarthria, and dysphagia. Aphasia was seen in 3 of 5 patients with left
      sided infarcts. Six of 8 patients (75%) had hypoperfusion as a possible
      pathogenetic factor (carotid occlusion in 4, surgical clipping of MCA in 1, low
      ejection fraction in 1), and 3 patients (38%) had cardioembolism as a possible
      pathogenetic factor (atrial fibrillation in 2, low ejection fraction in 1). One
      patient (12%) had no cause for stroke. Clinical features were similar to those
      for paraventricular infarcts. Carotid occlusion was more frequent (P=0.04), and
      there was a trend toward a higher frequency of hypertension (P<0.1) and smoking
      with DCIs than with paraventricular infarcts. DCIs were located in a deep
      vascular border zone. CONCLUSIONS: - The clinical features and pathogenesis of
      DCIs overlap with those of internal border zone paraventricular infarcts.
      Hypoperfusion may give rise to DCIs since large-artery occlusion is their main
      risk factor. The larger size of DCIs compared with paraventricular infarcts may
      relate to a poorer collateral blood supply.

PMID- 11588313
TI  - Right sylvian fissure subarachnoid hemorrhage has electrocardiographic
      consequences.
AB  - BACKGROUND AND PURPOSE: Abnormal ECG changes are frequently observed in patients
      with subarachnoid hemorrhage (SAH). Recently, evidence has been obtained that
      right insular cortex mediates sympathetic cardiovascular effects. We therefore
      assessed the laterality and location of SAH dominance in inducing cardiovascular
      changes as measured by ECG, blood pressure, and heart rate. METHODS: After
      exclusion of 11 SAH patients who died within 1 month after onset, we studied 118
      consecutive patients. Data were obtained from records of blood pressure and pulse
      on admission. Abnormal ECG changes were determined from ECGs on admission and
      almost 1 month later. From brain CT scans performed immediately after admission,
      the amount of SAH in each of the 8 cisterns and fissures was measured
      semiquantitatively. RESULTS: Twenty-six patients had abnormal changes on
      admission ECG, while 92 patients did not. Systolic blood pressure, diastolic
      blood pressure, and the amounts of blood in the left ambient cistern, left
      suprasellar cistern, quadrigeminal cistern, right ambient cistern, right
      suprasellar cistern, right sylvian fissure, and the set of all cisterns were
      significantly greater in the group with ECG change than in the group without ECG
      change. Multivariate logistic regression analysis with stepwise method indicated
      that systolic blood pressure >160 mm Hg (P=0.0006) and the amounts of SAH in the
      quadrigeminal cistern (P=0.022) and right sylvian fissure (P=0.0019) were
      independently associated with abnormal ECG change. CONCLUSIONS: Cardiac
      consequences are possible in patients with massive right sylvian fissure SAH or
      when systolic blood pressure is >160 mm Hg.

PMID- 11588314
TI  - Contrast-enhanced magnetic resonance angiography of the cervical vessels:
      experience with 422 patients.
AB  - BACKGROUND AND PURPOSE: Contrast-enhanced magnetic resonance angiography (CEMRA)
      permits acquisition of high-spatial-resolution, venous-suppressed, 3D MR
      angiograms of the cervical carotid and vertebral arteries. In this study, an
      elliptic centric-view ordering with either MR fluoroscopic triggering or test
      bolus timing was used. The use of CEMRA of the cervical vessels has changed our
      clinical practice and is replacing conventional angiography for the evaluation of
      most carotid and vertebral artery diseases. METHODS: We retrospectively reviewed
      our experience with the use of CEMRA performed in 422 patients from January
      through December 1999. RESULTS: CEMRA was performed to evaluate transient
      ischemic attack and ischemic stroke in 239 patients, asymptomatic carotid bruit
      in 88 patients, and other neurological symptoms in 95 patients. Carotid
      endarterectomies were performed in 97 patients (103 procedures), and conventional
      angiography was performed in 12 of these patients. CEMRA was used to evaluate for
      the presence of an arterial dissection in 85 of the 239 patients with transient
      ischemic attack and ischemic stroke. Of this group, 32 patients had cervical
      arterial dissection, and pseudoaneurysm was detected in 11 of these patients.
      Compared with ultrasonography of the cervical vessels, CEMRA provided additional
      information in 43 of 422 patients and led to changes in the decision as to
      whether to perform carotid endarterectomy in 5 patients. CONCLUSIONS: Use of
      CEMRA permits noninvasive evaluation of patients suspected of having carotid or
      vertebral disease and avoids the potential complications of conventional
      angiography.

PMID- 11588315
TI  - Role of conventional angiography in evaluation of patients with carotid artery
      stenosis demonstrated by Doppler ultrasound in general practice.
AB  - BACKGROUND AND PURPOSE: Previous studies have suggested that patients with
      carotid stenosis who are candidates for endarterectomy can be effectively
      identified on the basis of carotid Doppler ultrasound alone. Before widespread
      acceptance of this policy, the accuracy of carotid Doppler ultrasound outside
      selected centers and clinical trials needs to be evaluated. We performed a 12
      month prospective study to evaluate the accuracy of Doppler ultrasound in
      identifying patients for carotid intervention in general practice settings.
      METHODS: Each patient referred to our endovascular service for diagnostic
      angiography to evaluate for carotid stenosis was interviewed and examined by a
      neurologist. Subjects consisted of symptomatic patients with >/=50% stenosis and
      asymptomatic patients with >/=60% stenosis by Doppler ultrasound. Information
      pertaining to demographic and cerebrovascular risk factors and the results of the
      carotid Doppler ultrasound were recorded. The severity of stenosis on angiograms
      was measured with North American Symptomatic Carotid Endarterectomy Trial
      criteria by a blinded observer. The results of both studies were compared to
      determine the relative accuracy of ultrasound results. RESULTS: Of 130 patients
      (mean age, 69+/-8.8 years) who met Doppler ultrasound criteria, 22 (17%) and 8
      patients (6%) were found to have 30% to 49% or <30% stenosis by angiography,
      respectively. The positive predictive value of carotid Doppler ultrasound for
      identifying appropriate symptomatic candidates for carotid intervention
      (angiographic stenosis >/=50%) was 80%, with a false-positive value of 20%. The
      positive predictive value of carotid Doppler ultrasound for identifying
      appropriate asymptomatic candidates for carotid intervention (angiographic
      stenosis >/=60%) was 59%, with a false-positive value of 41%. Carotid
      endarterectomy or angioplasty and stent placement were undertaken subsequently in
      60 (46%) of the patients. In 94 patients who underwent cerebral angiography
      alone, no complications were observed. CONCLUSIONS: The present accuracy of
      carotid Doppler ultrasound in general practice does not justify its use as the
      sole basis of selecting appropriate patients for carotid intervention. Given the
      relatively low rate of associated morbidity with present day techniques,
      additional confirmatory studies such as angiography should be performed in every
      patient before a decision regarding intervention is made.

PMID- 11588316
TI  - Transcranial Doppler versus angiography in patients with vasospasm due to a
      ruptured cerebral aneurysm: A systematic review.
AB  - BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) is used for diagnosis of
      vasospasm in patients with subarachnoid hemorrhage due to a ruptured aneurysm.
      Our aim was to evaluate both the accuracy of TCD compared with angiography and
      its usefulness as a screening method in this setting. METHODS: A search (MEDLINE,
      EMBASE, Cochrane Library, bibliographies, hand searching, any language, through
      January 31, 2001) was performed for studies comparing TCD with angiography. Data
      were critically appraised using a modified published 10-point score and were
      combined using a random-effects model. RESULTS: Twenty-six reports compared TCD
      with angiography. Median validity score was 4.5 (range 1 to 8). Meta-analyses
      could be performed with data from 7 trials. For the middle cerebral artery (5
      trials, 317 tests), sensitivity was 67% (95% CI 48% to 87%), specificity was 99%
      (98% to 100%), positive predictive value (PPV) was 97% (95% to 98%), and negative
      predictive value (NPV) was 78% (65% to 91%). For the anterior cerebral artery (3
      trials, 171 tests), sensitivity was 42% (11% to 72%), specificity was 76% (53% to
      100%), PPV was 56% (27% to 84%), and NPV was 69% (43% to 95%). Three of these 7
      studies reported on the same patients, each on another artery, and for 4, data
      recycling could not be disproved. Other arteries were tested in only 1 trial
      each. CONCLUSIONS: For the middle cerebral artery, TCD is not likely to indicate
      a spasm when angiography does not show one (high specificity), and TCD may be
      used to identify patients with a spasm (high PPV). For all other situations and
      arteries, there is either lack of evidence of accuracy or of any usefulness of
      TCD. Most of these data are of low methodological quality, bias cannot not be
      ruled out, and data reporting is often uncritical.

PMID- 11588317
TI  - Effect of antiplatelet and anticoagulant agents on risk of hospitalization for
      bleeding among a population of elderly nursing home stroke survivors.
AB  - BACKGROUND AND PURPOSE: Anticoagulants and antiplatelet agents are underutilized
      in the nursing home setting, perhaps because trials demonstrating treatment
      efficacy excluded people resembling those with long-term care needs. We sought to
      quantify the effect of antiplatelet and anticoagulant agents on risk of
      hospitalization for bleeding among an elderly nursing home population. METHODS:
      We used a case-control design and identified first hospitalizations for bleeds
      using Medicare claims data from 1992 to 1997 as potential cases. Cases had at
      least one minimum data set (MDS) assessment within the 6 months before that
      hospitalization and a diagnosis of stroke. We identified up to 5 controls
      residing in the same facility during the same year and quarter as the case with a
      diagnosis of stroke. Our sample consisted of 3433 cases and 13 506 controls.
      Using the MDS, we identified standing orders for aspirin, dipyridamole,
      ticlopidine, or warfarin and used conditional logistic regression modeling to
      estimate the effect of these agents on risk of hospitalization for a bleed.
      RESULTS: After adjustment, use of warfarin (odds ratio [OR], 1.26; 95% CI, 1.11
      to 1.43) and combination therapy (OR, 1.34; 95% CI, 0.99 to 1.82) were associated
      with an increased risk of hospitalization for a bleed compared with nonusers. The
      odds of aspirin use was greater among cases than controls (OR, 1.07; 95% CI, 0.96
      to 1.18) after adjustment. CONCLUSIONS: Although present, the risk associated
      with use of these agents is small. The numbers needed to treat to harm 1 resident
      with aspirin and warfarin were 467 and 126, respectively.

PMID- 11588318
TI  - Procedural safety and short-term outcome of ambulatory carotid stenting.
AB  - BACKGROUND AND PURPOSE: Ambulatory procedures increase patient comfort and
      enhance cost-effectiveness. We sought to determine the feasibility and safety of
      ambulatory carotid stenting. METHODS: A selected group of patients was admitted
      and discharged the same day after the carotid stenting procedure. Immediate and
      short-term outcomes are reported. RESULTS: A total of 98 ambulatory carotid
      stenting procedures (98 hemispheres in 92 patients) were performed. There were 66
      men (72%), and the mean age was 70+/-9 years. Of the patients, 28% had
      neurological symptoms related to the treated artery within 3 months before the
      procedure. Sixteen percent of the patients had prior carotid endarterectomy, 4%
      had prior ipsilateral neck radiation, and 8% had complete occlusion of the
      contralateral internal carotid artery. Successful access site hemostasis was
      ensured in all patients with suture-mediated vascular closure devices in 96 (98%)
      and manual compression in 2. Clinical follow-up was available for 96% of the
      patients at a mean time of 6+/-4 months. There were no neurological events,
      deaths, repeated procedures, or major access site complications. CONCLUSIONS:
      Ambulatory carotid stenting is both safe and feasible. This approach will enhance
      the applicability of the procedure by increasing patient comfort and potentially
      reducing procedural costs.

PMID- 11588319
TI  - Nonrandomized comparison of local urokinase thrombolysis versus systemic heparin
      anticoagulation for superior sagittal sinus thrombosis.
AB  - BACKGROUND AND PURPOSE: We sought to compare the safety and efficacy of direct
      urokinase thrombolysis with systemic heparin anticoagulation for superior
      sagittal sinus thrombosis (SSST). METHODS: At University at Buffalo (NY) and
      University of Texas (Dallas, Houston), we reviewed 40 consecutive patients with
      SSST, treated with local urokinase (thrombolysis group) or systemic heparin
      anticoagulation (heparin group). The thrombolysis group (n=20) received local
      urokinase into the SSS followed by systemic heparin anticoagulation. The heparin
      group (n=20) received systemic heparin anticoagulation only. Neurological
      dysfunction was rated as follows: 0, normal; 1, mild (but able to ambulate and
      communicate); 2, moderate (unable to ambulate, normal mentation); and 3, severe
      (unable to ambulate, altered mentation). RESULTS: Age (P=0.49), sex (P=0.20),
      baseline venous infarction (P=0.73), and predisposing illnesses (P=0.52) were
      similar between the thrombolysis and heparin groups. Pretreatment neurological
      function was worse in the thrombolysis group (normal, n=5; mild, n=8; moderate,
      n=4; severe, n=3) than in the heparin group (normal, n=8; mild, n=8; moderate,
      n=3; severe, n=1) (P=NS). Discharge neurological function was better in the
      thrombolysis group (normal, n=16; mild, n=3; moderate, n=1; severe, n=0) than in
      the heparin group (normal, n=9; mild, n=6; moderate, n=5; severe, n=0) (P=0.019,
      Mann-Whitney U test). Hemorrhagic complications were 10% (n=2) in the
      thrombolysis group (subdural hematoma, retroperitoneal hemorrhage) and none in
      the heparin group (P=0.49). Three of the heparin group patients developed
      complications of the underlying disease (status epilepticus, hydrocephalus,
      refractory papilledema). No deaths occurred. Length of hospital stay was similar
      between the groups (P=0.79). CONCLUSIONS: Local thrombolysis with urokinase is
      fairly well tolerated and may be more effective than systemic heparin
      anticoagulation alone in treating SSST. A randomized, prospective study comparing
      these 2 treatments for SSST is warranted.

PMID- 11588320
TI  - Heterogeneity affecting outcome from acute stroke therapy: making reperfusion
      worse.
AB  - BACKGROUND: Stroke patients are heterogeneous not only with respect to etiology
      but also in terms of preexisting clinical conditions. Approximately one fifth of
      patients with acute stroke are hyperglycemic and/or have had a recent infectious
      or inflammatory condition. Summary of Review-- Experimental research indicates
      that these factors can alter and accelerate the evolution of stroke and
      reperfusion injury, although these effects are complex and some may have a
      favorable impact. Both conditions involve activation of inflammatory and reactive
      oxygen mechanisms. In addition, hyperglycemia has concomitant deleterious
      vascular and metabolic effects that worsen infarct size and encourage hemorrhagic
      transformation in reperfusion models. Clinical data are less extensive but in
      general support an adverse impact on outcome. CONCLUSIONS: After examining these
      data in detail, we concluded that the presence of these clinical conditions could
      assist in identification of those at increased risk for complications of
      reperfusion therapy. Furthermore, consideration of these factors may provide a
      rational basis for combination therapy and improve the clinical relevance of
      experimental stroke models.

PMID- 11588321
TI  - Initial experience of platelet glycoprotein IIb/IIIa inhibition with abciximab
      during carotid stenting: a safe and effective adjunctive therapy.
AB  - BACKGROUND AND PURPOSE: Abciximab has been shown to decrease periprocedural
      ischemic complications after coronary intervention. However, the adjunctive use
      of abciximab in carotid stenting has not been adequately studied. We sought to
      determine the efficacy and safety of abciximab in carotid stenting. METHODS:
      Carotid stenting was performed in 151 consecutive patients determined to be at
      high surgical risk by a vascular surgeon. Of these, 128 consecutive patients
      received adjuvant therapy with abciximab (0.25 mg/kg bolus before the lesion was
      crossed with guidewire and 0.125 micro. kg(-1). min(-1) infusion for 12 hours.).
      A heparin bolus of 50 U/kg was given, and activated clotting time was maintained
      between 250 to 300 seconds. All patients received aspirin and thienopyridine.
      Procedural and 30-day outcomes were compared between the control (n=23) and
      abciximab (n=128) groups. RESULTS: The 2 groups had similar baseline
      characteristics. Procedural events were more frequent in the control group (8%; 1
      major stroke and 1 neurological death) compared with the abciximab group (1.6%; 1
      minor stroke and 1 retinal infarction; P=0.05). On 30-day follow-up, 1 patient
      presented with delayed intracranial hemorrhage in the abciximab group. There were
      no other major bleeding complications. CONCLUSIONS: Adjunctive use of abciximab
      for carotid stenting is safe with no increase in the risk of intracranial
      hemorrhage. This adjunctive therapy with potent glycoprotein IIb/IIIa inhibition
      may help to reduce periprocedural adverse events in patients undergoing carotid
      stenting.

PMID- 11588323
TI  - Cocaine use is an independent risk factor for cerebral vasospasm after aneurysmal
      subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Although acute cocaine use has been temporally associated
      with aneurysmal subarachnoid hemorrhage (aSAH), the prevalence of vasospasm and
      the clinical outcome of patients experiencing aSAH associated with cocaine
      exposure are unclear. We have analyzed this patient population in our institution
      to address these issues. METHODS: Between 1992 and 1999, 440 patients presented
      to our institution with aSAH. This sample was retrospectively analyzed to
      determine which patients had used cocaine within 72 hours of aSAH as documented
      by urine toxicology studies or patient history. These patients were then compared
      with control aSAH patients without recent cocaine exposure through univariable
      and multivariable analyses. RESULTS: Twenty-seven aSAH patients (6.1% of total)
      had either urine toxicology positive for cocaine metabolites (20 patients, 74%)
      or a history of cocaine use within 72 hours of aSAH (7 patients, 26%). Cocaine
      users were more likely to experience cerebral vasospasm defined as a delayed
      clinical deficit (from 3 to 16 days after aSAH) unexplained by concurrent CT scan
      and either responsive to hypervolemic and/or hypertensive therapy or accompanied
      by angiographic confirmation of vessel narrowing than control subjects (63%
      versus 30%; odds ratio [OR], 3.90; 95% confidence interval [CI], 1.77 to 8.62;
      P=0.001). Patients using cocaine were younger than control subjects (mean age, 36
      versus 52 years; P<0.0001). Aneurysms of the anterior circulation were observed
      more frequently in cocaine users than in control subjects (97% versus 84%; OR,
      6.89; 95% CI, 1.18 to 47.47; P=0.029). A significant difference was not observed,
      however, in the discharge Glasgow Outcome Scale (GOS) scores between the 2 groups
      (P=0.73). Differences were not observed between the 2 groups when the
      distributions of sex, hypertension, admission Glasgow Coma Scale subarachnoid
      hemorrhage grade, and multiple aneurysms were analyzed. Logistic regression
      models identified variables independently associated with vasospasm and discharge
      GOS score. Only a thick blood clot on the admission CT (OR, 7.46; 95% CI, 3.95 to
      14.08; P<0.0001) and recent cocaine use (OR, 6.41; 95% CI, 2.14 to 19.23;
      P=0.0009) were independently associated with vasospasm. Cocaine use was not
      independently associated with the discharge GOS score. CONCLUSIONS: We conclude
      that there is an increased prevalence of vasospasm in aSAH patients with recent
      cocaine exposure but no difference in clinical outcome. In addition, these
      patients are younger and more likely to have anterior circulation aneurysms.

PMID- 11588322
TI  - Risk of early death and recurrent stroke and effect of heparin in 3169 patients
      with acute ischemic stroke and atrial fibrillation in the International Stroke
      Trial.
AB  - BACKGROUND AND PURPOSE: We sought to investigate the apparently high risk of
      early death after an ischemic stroke among patients with atrial fibrillation
      (AF), identify the main factors associated with early death, and assess the
      effect of treatment with different doses of subcutaneous unfractionated heparin
      (UFH) given within 48 hours. METHODS: We studied the occurrence of major clinical
      events within 14 days among 18 451 patients from the International Stroke Trial,
      first for all treatment groups combined. Then, among patients with AF, we
      examined the effects of treatment with subcutaneous UFH started within 48 hours
      and continued until 14 days after stroke onset. RESULTS: A total of 3169 patients
      (17%) had AF. Seven hundred eighty-four patients were allocated to UFH 12 500 IU
      SC BID, 773 to UFH 5000 IU SC BID, and 1612 to no heparin. Within each of these
      groups, half of the patients were randomly assigned to aspirin 300 mg once daily.
      Compared with patients without AF, patients with AF were more likely to be female
      (56% versus 45%), to be old (mean age, 78 versus 71 years), to have an infarct on
      prerandomization CT (57% versus 47%), and to have impaired consciousness (37%
      versus 20%). The initial ischemic stroke type was more often a large-artery
      infarct (36% versus 21%). A lacunar stroke syndrome was less common (13% versus
      26%). Death within 14 days was more common in patients with AF (17% versus 8%)
      and more often attributed to neurological damage from the initial stroke (10%
      versus 4%). The frequency of recurrent ischemic or undefined stroke was not
      significantly different (3.9% versus 3.3%). The proportion of AF patients with
      further events within 14 days allocated to UFH 12 500 IU (n=784), UFH 5000 IU
      (n=773), and to no-heparin (n=1612) groups were as follows: ischemic stroke,
      2.3%, 3.4%, 4.9% (P=0.001); hemorrhagic stroke, 2.8%, 1.3%, 0.4% (P<0.0001); and
      any stroke or death, 18.8%, 19.4% and 20.7% (P=0.3), respectively. No effect of
      heparin on the proportion of patients dead or dependent at 6 months was apparent.
      CONCLUSIONS: Acute ischemic stroke patients with AF have a higher risk of early
      death, which can be explained by older age and larger infarcts but not by a
      higher risk of early recurrent ischemic stroke, although slightly more patients
      with AF died from a fatal recurrent stroke of ischemic or unknown type (1.3%
      versus 0.9%). In patients with AF the absolute risk of early recurrent stroke is
      low, and there is no net advantage to treatment with heparin. These data do not
      support the widespread use of intensive heparin regimens in the acute phase of
      ischemic stroke associated with AF.

PMID- 11588324
TI  - Glutamate injury-induced epileptogenesis in hippocampal neurons: an in vitro
      model of stroke-induced "epilepsy".
AB  - BACKGROUND AND PURPOSE: Stroke is the major cause of acquired epilepsy. The
      mechanisms of ischemia-induced epileptogenesis are not understood, but glutamate
      is associated with both ischemia-induced injury and epileptogenesis in several
      models. The objective of this study was to develop an in vitro model of
      epileptogenesis induced by glutamate injury in hippocampal neurons as observed
      during stroke. METHODS: Primary hippocampal cultures were exposed to 5 micromol/L
      glutamate for various durations. Whole-cell current clamp electrophysiology was
      used to monitor the acute effects of glutamate on neurons and chronic alterations
      in neuronal excitability up to 8 days after glutamate exposure. RESULTS: A
      single, 30-minute, 5-micromol/L glutamate exposure produced a subset of neurons
      that died and a larger population of injured neurons that survived. Neuronal
      injury was characterized by prolonged reversible membrane depolarization, loss of
      synaptic activity, and neuronal swelling. Surviving neurons manifested
      spontaneous, recurrent, epileptiform discharges in neural networks characterized
      by paroxysmal depolarizing shifts and high-frequency spike firing that persisted
      for the life of the culture. CONCLUSIONS: This study demonstrates that glutamate
      injury produced a permanent epileptiform phenotype expressed as spontaneous,
      recurrent epileptiform discharges for the life of the hippocampal neuronal
      culture. These results suggest a novel in vitro model of glutamate injury-induced
      epileptogenesis that may help elucidate some of the mechanisms that underlie
      stroke-induced epilepsy.

PMID- 11588325
TI  - Endothelium-derived endothelin-1 reduces cerebral artery sensitivity to nitric
      oxide by a protein kinase C-independent pathway.
AB  - BACKGROUND AND PURPOSE: Nitric oxide (NO) reduces endothelin-1 (ET-1) production
      and blunts ET-1 dependent vasoconstriction. The direct effects of smooth muscle
      ET(A) receptor stimulation on NO-mediated relaxation are unknown. We hypothesized
      that endothelium-derived ET-1 regulates vascular tone by reducing smooth muscle
      sensitivity to NO, possibly through activation of protein kinase C (PKC).
      METHODS: Rings of rabbit middle cerebral artery were mounted on microvessel
      myographs to measure isometric tension. Dose-response curves to acetylcholine
      (ACh) and sodium nitroprusside (SNP; an NO donor) were obtained with or without
      ET-1 receptor blockade. Experiments were performed in the presence of
      indomethacin (10 micromol/L). Results are expressed as mean+/-SEM. RESULTS: In
      depolarized conditions (40 mmol/L KCl physiological solution), ACh-induced
      relaxation was entirely NO-dependent, as indicated by its suppression by N(omega)
      nitro-L-arginine (P<0.05). Arterial sensitivity (pD(2)) to ACh (6.32+/-0.11, n=6)
      was increased (P<0.05) to 6.77+/-0.10 (n=6) by BQ123 (ET(A) receptor antagonist,
      5 micromol/L) but not by BQ788 (ET(B) receptor antagonist, 5 micromol/L; 6.08+/
      0.22, n=5). Consistent with this finding, blockade of ET(A) receptors increased
      (P<0.05) vascular sensitivity to SNP (6.95+/-0.10, n=8), whereas BQ788 had no
      influence on arterial sensitivity to SNP (6.17+/-0.07, n=7) compared with control
      (6.43+/-0.13, n=11). In denuded arteries, the sensitivity to SNP (7.10+/-0.08,
      n=8) was reduced by exogenous ET-1 (6.51+/-0.35, n=7, P<0.05). Chelerythrine, a
      PKC inhibitor, did not alter smooth muscle sensitivity to NO, whereas phorbol 12
      myristate 13-acetate, a PKC activator, strongly increased it. CONCLUSIONS:
      Blockade of ET(A) but not ET(B) receptors sensitizes vascular smooth muscle to
      exogenous and endothelium-derived NO. This suggests that ET-1 regulates smooth
      muscle sensitivity to NO by a PKC-independent pathway. This represents an
      alternative pathway by which NO and ET-1 interact to regulate vascular tone.

PMID- 11588326
TI  - Superoxide during reperfusion contributes to caspase-8 expression and apoptosis
      after transient focal stroke.
AB  - BACKGROUND AND PURPOSE: Reactive oxygen species produced during reperfusion may
      play a detrimental role in focal cerebral ischemia (FCI). We examined the protein
      expression of caspase-8, which plays a major role in both Fas-dependent and
      cytochrome c-dependent apoptotic pathways after FCI with or without reperfusion.
      Caspase-8 expression after transient FCI was compared between wild-type and
      transgenic mice that overexpress the cytosolic antioxidant copper/zinc superoxide
      dismutase (SOD1). METHODS: Adult male CD-1 mice were subjected to 1 hour of FCI
      and reperfusion or to permanent FCI by intraluminal blockade of the middle
      cerebral artery. DNA fragmentation was evaluated by genomic DNA gel
      electrophoresis. Caspase-8 expression was analyzed by Western blot. RESULTS:
      Caspase-8 was significantly induced 4 hours after transient FCI and remained at
      an increased level until 24 hours, whereas it was not modified after permanent
      FCI. Genomic DNA gel electrophoresis showed DNA laddering in a pattern similar to
      that seen in apoptosis, with a small amount of background smear 24 hours after
      transient FCI, whereas 25 hours of permanent FCI resulted in less DNA laddering
      with a strong background smear. Caspase-8 induction was significantly reduced in
      SOD1 transgenic mice compared with wild-type mice 4 hours after transient FCI.
      CONCLUSIONS: The results suggest that increased reactive oxygen species
      production during reperfusion may contribute to the induction of caspase-8,
      thereby exacerbating apoptosis after FCI.

PMID- 11588327
TI  - Reversal of early diffusion-weighted magnetic resonance imaging abnormalities
      does not necessarily reflect tissue salvage in experimental cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted MRI (DWI) can detect early ischemic
      changes and is sometimes used as a surrogate neurological end point in clinical
      trials. Recent experimental stroke studies have shown that with brief periods of
      ischemia, some DWI lesions transiently reverse, only to recur later. This study
      examined the histological condition of the tissue during the period of DWI
      reversal. METHODS: Rats underwent 30 minutes of middle cerebral artery occlusion
      followed by reperfusion. DWI images were obtained during ischemia and 3 to 5
      hours, 1 day, and 7 days later. MRI scans were compared with histology (5 hours,
      n=5; 7 days, n=5) with the use of neuronal (microtubule-associated protein 2
      [MAP2]) and astrocytic (glial fibrillary acidic protein [GFAP]) markers and heat
      shock protein 72 (HSP72). RESULTS: DWI abnormalities reversed 3 to 5 hours after
      ischemia onset but recurred at 1 day. Four animals showed complete reversal of
      the initial DWI hyperintensity, and 6 showed partial reversal. When the 5-hour
      DWI was completely normal, there was significant loss of MAP2 immunoreactivity,
      comprising approximately 30% of the initial DWI lesion. However, GFAP staining
      revealed morphologically normal astrocytes. HSP72 immunoreactivity at 5 hours was
      extensive and corresponded to the initial DWI lesion. CONCLUSIONS: After brief
      ischemic periods, normalization of the DWI does not necessarily imply that the
      tissue is normal. Neurons already exhibit evidence of structural damage and
      stress. Normal GFAP staining suggests that other nonneuronal cell populations may
      partially compensate for altered fluid balances at the time of DWI reversal
      despite the presence of neuronal injury. These observations suggest that caution
      is warranted when relying solely on DWI for assessment of ischemic damage.

PMID- 11588328
TI  - Cyclooxygenase-2 inhibitor ns-398 protects neuronal cultures from
      lipopolysaccharide-induced neurotoxicity.
AB  - BACKGROUND AND PURPOSE: The prostanoid-synthesizing enzyme cyclooxygenase (COX)-2
      is markedly upregulated after cerebral ischemia and may participate in the
      mechanisms by which postischemic inflammation contributes to the late stages of
      ischemic brain injury. In the present study, we sought to provide additional
      evidence for a role of COX-2 in the mechanisms of neurotoxicity associated with
      inflammation. METHODS: Nine-day-old neuronal-glial cultures, prepared from the
      cerebral cortex of newborn C57BL/6J mice, were exposed to lipopolysaccharide
      (LPS), a potent proinflammatory agent. The contribution of COX-2 was investigated
      by using the COX-2 inhibitor NS-398. RESULTS: LPS produced a dose-dependent
      (0.001 to 10 microg/mL) and selective neuronal death that was well developed 72
      hours after treatment. The effect was associated with a marked increase in the
      concentration of the COX reaction product prostaglandin E(2) (PGE(2)) and of the
      cytokine tumor necrosis factor-alpha (TNF-alpha). NS-398 (10 micromol/L) blocked
      the PGE(2) increase, attenuated the TNF-alpha increase, and prevented the
      neuronal death produced by LPS. TNF-alpha-blocking antibodies attenuated LPS
      induced neuronal death, but the protection was less pronounced than that afforded
      by NS-398. LPS failed to elevate PGE(2) or to produce cell death in neuron
      enriched cultures, suggesting that glial cells are required for these effects.
      CONCLUSIONS: COX-2, in part through TNF-alpha-related mechanisms, contributes to
      LPS-induced neuronal death. The data support the hypothesis that COX-2, in
      addition to its role in glutamate excitotoxicity, participates in the
      cytotoxicity associated with inflammation.

PMID- 11588329
TI  - Effects of citicoline on phospholipid and glutathione levels in transient
      cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Cytidine-5'-diphosphocholine (citicoline or CDP-choline)
      is an essential intermediate in the biosynthesis of phosphatidylcholine, an
      important component of the neural cell membrane. Citicoline provided significant
      neuroprotection after transient forebrain ischemia in gerbils. This study was
      undertaken to examine changes and effects of citicoline on phospholipids and
      glutathione synthesis after transient cerebral ischemia and reperfusion. METHODS:
      Ten-minute transient forebrain ischemia was induced by bilateral carotid artery
      occlusion in male Mongolian gerbils with reperfusion up to 6 days. Citicoline
      (500 mg/kg IP in saline) was given to gerbils just after the end of ischemia, at
      3-hour reperfusion, and daily thereafter until 1 day before euthanasia.
      Hippocampal lipids were extracted and analyzed by thin-layer and gas
      chromatography. Glutathione was measured by using an enzymatic recycling assay.
      Glutathione reductase activity was determined by measuring NADPH oxidation.
      RESULTS: Significant decreases in phospholipids occurred at 1-day reperfusion.
      Citicoline significantly restored the phosphatidylcholine, sphingomyelin, and
      cardiolipin levels but did not affect phosphatidylinositol and phosphatidylserine
      at 1 day. The phospholipids returned to sham levels over days 2 to 6 and were
      unaffected by citicoline. Ceramide levels significantly increased by 3 and 6 days
      of reperfusion and were unaltered by citicoline. Ischemia resulted in significant
      decreases in glutathione and glutathione reductase activity over 3 days of
      reperfusion. Citicoline significantly increased total glutathione and glutathione
      reductase activity and decreased the glutathione oxidation ratio, an indicator of
      glutathione redox status. CONCLUSIONS: Our data indicated that the effects of
      citicoline on phospholipids occurred primarily during the first day of
      reperfusion, with effects on glutathione being important over the 3-day
      reperfusion period.

PMID- 11588330
TI  - Reduction and restoration of mitochondrial dna content after focal cerebral
      ischemia/reperfusion.
AB  - BACKGROUND AND PURPOSE: Oxidative damage of mitochondrial DNA (mtDNA) in the
      ischemic brain is expected after ischemia/reperfusion injury. A recent study
      demonstrated limited patterns of mtDNA deletion in the brain after
      ischemia/reperfusion. We studied the ischemia/reperfusion-induced global changes
      of mtDNA integrity and its restoration in a rat model of transient focal ischemia
      in vivo. METHODS: Changes in mtDNA content in the ischemic brain were assessed
      with the use of a rat stroke model featuring transient severe ischemia confined
      to the cerebral cortex of the right middle cerebral artery territory for 30 or 90
      minutes. A new long polymerase chain reaction method, using mouse DNA as an
      internal standard, was applied to measure the relative content of intact rat
      mtDNA. Southern hybridization following alkaline gel electrophoresis was
      conducted in a parallel study to confirm long polymerase chain reaction results.
      RESULTS: A reduction in mtDNA content was found after ischemia for 30 and 90
      minutes. The mtDNA was restored to near nonischemic levels 24 hours after 30- but
      not 90-minute ischemia. CONCLUSIONS: These results confirm that
      ischemia/reperfusion causes mtDNA damages. Restoration of the mtDNA content to
      nonischemic levels after 30-minute ischemia raises the possibility that mtDNA
      repair or repletion occurs after brief ischemia.

PMID- 11588331
TI  - Neuronal expression of the DNA repair protein Ku 70 after ischemic
      preconditioning corresponds to tolerance to global cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Oxidative stress after ischemia/reperfusion has been
      shown to induce DNA damage and subsequent DNA repair activity. Ku 70/86,
      multifunctional DNA repair proteins, bind to broken DNA ends and trigger a DNA
      repair pathway. We investigated the involvement of these proteins in the
      development of neuronal tolerance to global cerebral ischemia after ischemic
      preconditioning. METHODS: Adult male Sprague-Dawley rats were subjected to either
      5 minutes of lethal global ischemia with or without 3 minutes of sublethal
      ischemic preconditioning or 3 minutes of ischemia only. Neuronal injury was
      histologically assessed, and DNA damage was visualized by in situ labeling of DNA
      fragmentation and DNA gel electrophoresis. Ku expression was also examined by
      immunohistochemistry and Western blot analysis. RESULTS: Hippocampal CA1 neurons
      underwent DNA-fragmented cell death 3 days after 5 minutes of ischemia. However,
      these neurons showed a strong tolerance to 5 minutes of ischemia 1 to 3 days
      after ischemic preconditioning. Immunohistochemistry showed virtually no
      constitutive expression of Ku proteins in CA1 neurons; however, ischemic
      preconditioning induced neuronal Ku 70 expression 1 to 3 days later. Western blot
      confirmed an increase in Ku 70 in this region at the same time. CONCLUSIONS: The
      temporal and spatial expression of Ku 70 corresponded to tolerance of the
      hippocampal CA1 neurons to subsequent ischemia, suggesting the involvement of Ku
      proteins in the development of neuronal tolerance after ischemic preconditioning.

PMID- 11588332
TI  - Triflusal posttreatment inhibits glial nuclear factor-kappaB, downregulates the
      glial response, and is neuroprotective in an excitotoxic injury model in
      postnatal brain.
AB  - BACKGROUND AND PURPOSE: Nuclear factor-kappaB (NF-kappaB) and the signal
      transducer and activator of transcription 3 (STAT3) are important transcription
      factors regulating inflammatory mechanisms and the glial response to neural
      injury, determining lesion outcome. In this study we evaluate the ability of
      triflusal (2-acetoxy-4-trifluoromethylbenzoic acid), an antiplatelet agent
      inhibitor of NF-kappaB activation, to improve lesion outcome after excitotoxic
      damage to the immature brain. METHODS: Postnatal day 9 rats received an
      intracortical injection of the excitotoxin N-methyl-D-aspartate (NMDA) and oral
      administration of triflusal (30 mg/kg) either as 3 doses before NMDA injection
      (pretreatment) or as a single dose 8 hours after NMDA injection (posttreatment).
      After survival times of 10 and 24 hours, brains were processed for toluidine blue
      staining, tomato lectin histochemistry, and glial fibrillary acidic protein, NF
      kappaB, and STAT3 immunocytochemistry. RESULTS: NMDA-lesioned animals that were
      not treated with triflusal showed activation of NF-kappaB in neuronal cells at
      first and in glial cells subsequently. Animals that received pretreatment with
      triflusal showed a strong downregulation of neuronal and glial NF-kappaB but a
      similar development of the glial response and an equivalent lesion volume
      compared with nontreated animals. In contrast, animals receiving triflusal
      posttreatment showed increased early neuronal NF-kappaB but a reduction in the
      subsequent glial NF-kappaB, accompanied by important downregulation of the
      microglial and astroglial response and a drastic reduction in the lesion size.
      STAT3 activation was not affected by triflusal treatment. CONCLUSIONS: Triflusal
      posttreatment diminishes glial NF-kappaB, downregulates the glial response, and
      improves the lesion outcome, suggesting a neuroprotective role of this compound
      against excitotoxic injury in the immature brain.

PMID- 11588334
TI  - Cost of stroke in Australia from a societal perspective: results from the North
      East Melbourne Stroke Incidence Study (NEMESIS).
AB  - BACKGROUND AND PURPOSE: Accurate information about resource use and costs of
      stroke is necessary for informed health service planning. The purpose of this
      study was to determine the patterns of resource use among stroke patients and to
      estimate the total costs (direct service use and indirect production losses) of
      stroke (excluding SAH) in Australia for 1997. METHODS: An incidence-based cost-of
      illness model was developed, incorporating data obtained from the North East
      Melbourne Stroke Incidence Study (NEMESIS). The costs of stroke during the first
      year after stroke and the present value of total lifetime costs of stroke were
      estimated. RESULTS: The total first-year costs of all first-ever-in-a lifetime
      strokes (SAH excluded) that occurred in Australia during 1997 were estimated to
      be A$555 million (US$420 million), and the present value of lifetime costs was
      estimated to be A$1.3 billion (US$985 million). The average cost per case during
      the first 12 months and over a lifetime was A$18 956 (US$14 361) and A$44 428
      (US$33 658), respectively. The most important categories of cost during the first
      year were acute hospitalization (A$154 million), inpatient rehabilitation (A$150
      million), and nursing home care (A$63 million). The present value of lifetime
      indirect costs was estimated to be A$34 million. CONCLUSIONS: Similar to other
      studies, hospital and nursing home costs contributed most to the total cost of
      stroke (excluding SAH) in Australia. Inpatient rehabilitation accounts for
      approximately 27% of total first-year costs. Given the magnitude of these costs,
      investigation of the cost-effectiveness of rehabilitation services should become
      a priority in this community.

PMID- 11588333
TI  - Critical analysis of cerebrovascular autoregulation during repeated head-up tilt.
AB  - BACKGROUND AND PURPOSE: Cerebrovascular autoregulation has been described with a
      phase lead of cerebral blood flow preceding changes in cerebral perfusion
      pressure (CPP), but there has been less focus on the effect of CPP on cerebral
      vascular resistance. We investigated these relations during spontaneous
      fluctuations (control) and repeated head-up tilt. METHODS: Eight healthy adults
      were studied in supine rest and repeated tilt with 10-second supine, 10 seconds
      at 45 degrees head-up tilt for a total of 12 cycles. Cerebral blood flow was
      estimated from mean flow velocity (MFV) by transcranial Doppler ultrasound, CPP
      was estimated from corrected finger pressure (CPP(F)), and cerebrovascular
      resistance index (CVRi) was calculated in the supine position from CPP(F)/MFV.
      Gain and phase relations were assessed by cross-spectral analysis. RESULTS: In
      the supine position, MFV preceded CPP(F), but changes in CVRi followed CPP(F).
      Gain and phase relations for CPP(F) as input and MFV as output were similar in
      supine and repeated tilt experiments. Thus, changes in cerebrovascular resistance
      must have had a similar pattern in the supine and tilt experiments. CONCLUSIONS:
      Cerebrovascular autoregulation is achieved by changes in resistance in response
      to modulations in perfusion pressure whether spontaneous or induced by repeated
      tilt. The phase lead of MFV before CPP(F) is a mathematical and physiological
      consequence of the relation the input variable (CPP(F)) and the manipulated
      variable (cerebrovascular resistance) that should not be taken as an indication
      of independent control of cerebral blood flow.

PMID- 11588335
TI  - Geographic variation in the rate of carotid endarterectomy in Canada.
AB  - Background and Purpose-- Carotid endarterectomy (CEA) is an important method of
      stroke prevention, but its usage in Canada is not well known. The indications for
      CEA have been well informed by the recent clinical trials, but the impact of this
      information on the rate and regional variation in the rate of CEA is unknown.
      This study sought to determine the rate and the regional variation in the rate of
      CEA in Canada, its provinces, and census divisions for 1994-1997. METHODS:
      Discharge data from all hospitals in Canada except Quebec were obtained from the
      Canadian Institute for Health Information for 1994-1997 and were searched for CEA
      by residential site. Rates and variations in rates were calculated. RESULTS: The
      national age- and sex-adjusted rate per 100 000 people of CEA for those aged
      >/=40 years rose from 31.7 in 1994 to 40.5 in 1997. Provincial rates in 1997
      varied from a low of 25.7 in Saskatchewan to high of 82.8 in Prince Edward
      Island. The census division rates varied even more, from a low of 0 in several
      divisions to a high of 179. CONCLUSIONS: The recent slight increase in CEA rates
      may reflect the release of new efficacy results for CEA, especially for
      asymptomatic carotid stenosis, but the rates are still far below US levels. The
      marked regional variation in rates may reflect differing views on the
      appropriateness of indications such as asymptomatic carotid stenosis for CEA and
      the inconsistency of published clinical practice guidelines.

PMID- 11588336
TI  - Early stroke: a dynamic process.

PMID- 11588337
TI  - Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic
      patients: a systematic overview.
AB  - BACKGROUND AND PURPOSE: "Stress" hyperglycemia may be associated with increased
      mortality and poor recovery in diabetic and nondiabetic patients after stroke. A
      systematic review and meta-analysis of the literature relating acute poststroke
      glucose levels to the subsequent course were done to summarize and quantify this
      relationship. METHODS: A comprehensive literature search was done for cohort
      studies reporting mortality and/or functional recovery after stroke in relation
      to admission glucose level. Relative risks in hyperglycemic compared with
      normoglycemic patients with and without diabetes were calculated and meta
      analyzed when possible. RESULTS: Thirty-two studies were identified; relative
      risks for prespecified outcomes were reported or could be calculated in 26
      studies. After stroke of either subtype (ischemic or hemorrhagic), the unadjusted
      relative risk of in-hospital or 30-day mortality associated with admission
      glucose level >6 to 8 mmol/L (108 to 144 mg/dL) was 3.07 (95% CI, 2.50 to 3.79)
      in nondiabetic patients and 1.30 (95% CI, 0.49 to 3.43) in diabetic patients.
      After ischemic stroke, admission glucose level >6.1 to 7.0 mmol/L (110 to 126
      mg/dL) was associated with increased risk of in-hospital or 30-day mortality in
      nondiabetic patients only (relative risk=3.28; 95% CI, 2.32 to 4.64). After
      hemorrhagic stroke, admission hyperglycemia was not associated with higher
      mortality in either diabetic or nondiabetic patients. Nondiabetic stroke
      survivors whose admission glucose level was >6.7 to 8 mmol/L (121 to 144 mg/dL)
      also had a greater risk of poor functional recovery (relative risk=1.41; 95% CI,
      1.16 to 1.73). CONCLUSIONS: Acute hyperglycemia predicts increased risk of in
      hospital mortality after ischemic stroke in nondiabetic patients and increased
      risk of poor functional recovery in nondiabetic stroke survivors.

PMID- 11588338
TI  - Nimodipine in animal model experiments of focal cerebral ischemia: a systematic
      review.
AB  - BACKGROUND AND PURPOSE: Based on the results of animal experiments, clinical
      trials were performed with nimodipine, which did not demonstrate a beneficial
      effect on outcome after stroke. The aim of this study was to determine whether
      the evidence from animal experiments with nimodipine supported the use of
      nimodipine in clinical trials. METHODS: - We performed a systematic review of
      animal experiments with nimodipine in focal cerebral ischemia. Studies were
      identified by searching Medline and Embase. We assessed whether these studies
      showed a beneficial effect of active treatment. In-depth analyses were performed
      on infarct size and amount of edema, and subgroup analyses were performed on the
      length of the time window to the initiation of treatment and the methodological
      quality of the studies. RESULTS: - Of 225 identified articles, 20 studies were
      included. The methodological quality of the studies was poor. Of the included
      studies, 50% were in favor of nimodipine. In-depth analyses showed statistically
      significant effects in favor of treatment (10 studies). No influence of the
      length of time to the initiation of treatment or of the methodological quality on
      the results was found. CONCLUSIONS: - We conclude that the results of this review
      did not show convincing evidence to substantiate the decision to perform trials
      with nimodipine in large numbers of patients. There were no differences between
      the results of the animal experiments and clinical studies. Surprisingly, we
      found that animal experiments and clinical studies ran simultaneously.

PMID- 11588339
TI  - Racism and tPA use in African-Americans.

PMID- 11588340
TI  - Life-threatening complications from spinal manipulation are rare.

PMID- 11588341
TI  - Re: utilization of intravenous tissue-type plasminogen activator for ischemic
      stroke at academic medical centers.

PMID- 11588342
TI  - Is retrospective study reliable in genetic studies?

PMID- 11588343
TI  - Retinal and cerebral artery embolism after "shiatsu" on the neck.

PMID- 11588344
TI  - IMT for the elderly?

PMID- 11588345
TI  - Re: Chlamydia pneumoniae does not influence atherosclerotic plaque behavior in
      patients with established carotid artery stenosis.

PMID- 11588346
TI  - Inflammation, statins, and outcome after ischemic stroke.

PMID- 11588347
TI  - A novel TCD grading system for residual flow in stroke patients.

PMID- 11588348
TI  - YCu3Al2, an example of an AB5 structure type.
AB  - Yttrium tricopper dialuminium, YCu(3)Al(2), is isostructural with hexagonal
      CaCu(5), in which each Cu atom at the 3g((1/2),0,(1/2)) position in space group
      P6/mmm (No. 191) is partially replaced by an Al atom. The hydrogen-uptake
      properties are usually enhanced in other AB(5) structures by aluminium
      substitution. YCu(5) does not show any hydrogen absorption, and the goal of the
      present work is to investigate whether aluminium substitution could expand the
      metal-atom lattice enough to provide better interstitial positions for hydrogen
      storage. However, no enthalpy change was observed up to 773 K under 3 MPa static
      H(2) pressure by differential thermal analysis (DTA) for the title compound. The
      compound does not show any significant hydrogen absorption/desorption in the
      pressure-composition isotherms (P-C-T diagrams) in the temperature range 298-673
      K under 3.3 MPa H(2) pressure.

PMID- 11588349
TI  - Pyrochlore-type tin niobate.
AB  - A single crystal of Sn(1.59)Nb(1.84)O(6.35) was grown at 1273 K from a mixture of
      sodium niobate and tin(II) chloride. The structure is of pyrochlore type
      A(2)B(2)O(7). The tin is partially oxidized to tin(IV) and competes with niobium
      for the occupation of site B. The stereoactivity of the Sn(2+) lone pair induces
      displacement of tin towards the O atoms of the tunnel.

PMID- 11588350
TI  - Indium tellurium trioxide chloride, InTeO3Cl.
AB  - The new oxychloride InTeO(3)Cl was synthesized from a mixture of In(2)O(3),
      InCl(3) and TeO(2). Its structure has been determined from single-crystal X-ray
      diffraction data. The structure is composed of layers separated by a van der
      Waals gap. The layers consist of edge-sharing chains of [InO(4)Cl(2)] octahedra
      linked through [TeO(3)] trigonal pyramids. No free Cl atoms are located between
      the layers.

PMID- 11588351
TI  - A synchrotron X-ray study of triclinic LiCa2Nb3O10 with perovskite-type slabs.
AB  - The triclinic superstructure of a small crystal of LiCa(2)Nb(3)O(10), lithium
      dicalcium triniobium decaoxide, has been investigated by synchrotron X-ray
      diffraction. The unit cell is an almost rectangular parallelepiped, although
      there is a 0.245 degrees offset from orthogonality for beta. The structure
      essentially belongs to a homologous series of Li[Na(n-3)Ca(2)Nb(n)O(3n+1)] with n
      = 3, where the moiety in square brackets has a perovskite-type slab structure.
      The superstructure has a doubled unit-cell volume with respect to the tetragonal
      aristotype. The NbO(6) octahedra are rotated about axes parallel to [110] by
      approximately 10 degrees. Adjacent slabs are connected by Li atoms and are
      geometrically related by 4(2) pseudosymmetry lying parallel to c. There are twice
      as many sites as Li atoms, providing a variation of population at these Li sites.

PMID- 11588352
TI  - Li2AlB5O10.
AB  - A new compound, dilithium aluminium pentaborate, Li(2)AlB(5)O(10), has been
      synthesized by solid-state reaction and its structure determined by single
      crystal X-ray diffraction. This compound is composed of [B(5)O(10)](5-) groups
      linked by AlO(4) tetrahedra. The [B(5)O(10)](5-) group consists of two hexagonal
      B-O rings perpendicular to each other connected by tetracoordinated boron. All
      the B-O rings in this structure can be divided into two groups, with one group
      approximately parallel and the other perpendicular to the c axis.

PMID- 11588353
TI  - beta-CdC2O4.
AB  - Crystals of anhydrous cadmium oxalate, beta-[Cd(C(2)O(4))], have been synthesized
      hydrothermally and the crystal structure solved using single-crystal X-ray
      diffraction data. The Cd and oxalate ions lie about independent inversion
      centres. The structure consists of a three-dimensional framework built from
      sheets of cadmium octahedra linked together by oxalate groups.

PMID- 11588354
TI  - [2,13-Bis(acetamido)-5,16-dimethyl-2,6,13,17
      tetraazatricyclo[16.4.0.07,12]docosane]copper(II) dichloride octahydrate.
AB  - The title compound, [Cu(C(24)H(46)N(6)O(2))]Cl(2).8H(2)O, contains a
      centrosymmetric cation, with the anions and water molecules on general sites. The
      coordination geometry around the Cu(II) ion is an axially elongated octahedron,
      with Cu-N distances of 2.0448 (17) and 2.0847 (17) A, and a Cu-O1 distance of
      2.3138 (16) A.

PMID- 11588356
TI  - Bis(mu-3,5-di-tert-butylcatecholato-O1:O1,O2)bis[tris(pyridine-N)cadmium(II)]
      dipyridine solvate.
AB  - X-ray diffraction shows that the title cadmium(II) complex,
      [Cd(2)(C(14)H(20)O(2))(2)(C(5)H(5)N)(6)].2C(5)H(5)N, has a dimeric structure in
      which two (py)(3)Cd(3,5-di-tert-butylcatecholate) units (py is pyridine) are
      connected by two bridging O atoms, the coordination of the Cd atoms being
      distorted octahedral. There are two symmetrically independent dimers in the
      crystal structure; one is in a general position and the other lies about an
      inversion centre. In both cases, the bridging Cd-O distances between the Cd
      catecholate units [2.224 (2)-2.237 (2) A] are shorter than the bridging Cd-O
      distances within the catecholate cycle [2.273 (2)-2.281 (2) A]. The Cd-N(py)
      distances are 2.354 (2)-2.471 (2) A. Besides the main molecules, the crystal also
      contains pyridine solvate molecules.

PMID- 11588355
TI  - On the short carbonyl bond in bis[mu-1,2-benzisothiazol-3(2H)-one 1,1-dioxido
      kappa2N:O]bis[[1,2-benzisothiazol-3(2H)-one 1,1-dioxido
      kappaN]bis(imidazole)copper(II)].
AB  - The short carbonyl bond in the title compound,
      [Cu(2)(C(7)H(4)NO(3)S)(4)(C(3)H(4)N(2))(4)] [Liu, Huang, Li & Lin (1991). Acta
      Cryst. C47, 41-43], is an artifact of disorder in the isothiazol-3(2H)-one 1,1
      dioxide part of the 1,2-benzisothiazol-3(2H)-one entity. In the present
      redetermination, all bond dimensions in the centrosymmetric dinuclear molecule
      are normal. The five-coordinate Cu atom shows trigonal-bipyramidal coordination.
      Hydrogen bonds from the imidazole donor ligand link adjacent molecules into a two
      dimensional layer structure.

PMID- 11588357
TI  - 2-Methyl-1-(4-nitrobenzyl)pyridinium bis(maleonitriledithiolato)nickelate(III).
AB  - In the title complex, 2-methyl-1-(4-nitrobenzyl)pyridinium bis(1,2-dicyanoethene
      1,2-dithiolato)nickelate(III), (C(13)H(13)N(2)O(2))[Ni(C(4)N(2)S(2))(2)], the
      most prominent general structural feature of the complex is the completely
      segregated columnar stacks of anions and cations. Within the cation column, there
      may be stacking interactions between adjacent nitro groups and benzene rings.

PMID- 11588358
TI  - Tetrakis(mu-acetato-O,O')bis[(4-cyanopyridine-N)copper(II)].
AB  - The title compound, [Cu(2)(C(2)H(3)O(2))(4)(C(6)H(4)N(2))(2)], has the familiar
      lantern-type structure that is characteristic of dimetal tetracarboxylates of
      copper and several other transition elements. The molecule lies about an
      inversion centre and the Cu atom is present in a distorted square-pyramidal
      coordination environment, consisting of four O atoms in equatorial positions and
      the pyridyl-N atoms of the two 4-cyanopyridine ligands in axial positions.

PMID- 11588359
TI  - [Ni(terpy)(H2O)]-trans-[Ni-(mu-CN)2-(CN)2]n, a one-dimensional linear
      tetracyanonickelate chain.
AB  - The one-dimensional chain catena-poly[[aqua(2,2':6',2"-terpyridyl
      kappa(3)N)nickel(II)]-mu-cyano-kappa(2)N:C-[bis(cyano-kappaC)nickelate(II)]-mu
      cyano-kappa(2)C:N], [Ni(terpy)(H(2)O)]-trans-[Ni-mu-(CN)(2)-(CN)(2)](n) or
      [Ni(2)(CN)(4)(C(15)H(11)N(3))(H(2)O)], consists of infinite linear chains along
      the crystallographic [10-1] direction. The chains are composed of two distinct
      types of nickel ions, paramagnetic octahedral [Ni(terpy)(H(2)O)](2+) cations
      (with twofold crystallographic symmetry) and diamagnetic planar [Ni(CN)(4)](2-)
      anions (with the Ni atom on an inversion center). The [Ni(CN)(4)](2-) units act
      as bidentate ligands bridging through two trans cyano groups thus giving rise to
      a new example of a trans-trans chain among planar tetracyanonickelate complexes.
      The coordination geometry of the planar nickel unit is typical of slightly
      distorted octahedral nickel(II) complexes, but for the [Ni(CN)(4)](2-) units, the
      geometry deviates from a planar configuration due to steric interactions with the
      terpyridine ligands.

PMID- 11588360
TI  - Bis(tetraphenylphosphonium) tris(oxalato-O,O')germanate(IV).
AB  - The synthesis and structure of the title compound,
      (C(24)H(20)P)(2)[Ge(C(2)O(4))(3)], are reported. The PPh(4)(+) cations in the
      structure form infinite zigzag chains in which the P.P distances alternate
      between 6.229 (1) and 7.118 (1) A, and the P.P.P angle is 131.4 (1) A. The
      shorter P.P distance is associated with a sixfold phenyl embrace. However, the
      longer P.P distance is associated with both phenyl-phenyl interactions and
      interactions between the cations and a twofold symmetric [Ge(C(2)O(4))(3)](2-)
      anion. In the cation-anion interactions, the P.O distance is 4.444 (2) A, the O.P
      C(distal) angle is 175.0 (1) degrees and the shortest H.O distances are 2.74 and
      3.09 A.

PMID- 11588361
TI  - Tetrakis(2-amino-5-methyl-1,3,4-thiadiazole-N3)chlorocopper(II) chloride
      monohydrate and tetrakis(2-amino-5-ethyl-1,3,4-thiadiazole-N3)chlorocopper(II)
      chloride.
AB  - The structures of the title compounds, [CuCl(C(3)H(5)N(3)S)(4)]Cl.H(2)O, (I), and
      [CuCl(C(4)H(7)N(3)S)(4)]Cl, (II), comprise square-pyramidal Cu centres with four
      N-bound organic ligands filling the base positions, a Cl atom in the apical
      position and a Cl(-) as a free counter-ion. The cation and free chloride ion in
      (II) have fourfold crystallographic symmetry. Hydrogen-bonding associations from
      the 2-amino H atoms dominate both structures, with the principal acceptors being
      the chlorides, although in (I), the N4 atoms are also involved. Furthermore, (I)
      is a hydrate, with the water molecule participating in the hydrogen-bonding
      network.

PMID- 11588362
TI  - trans-Bis(2-amino-6-nitro-1,3-benzothiazole-N)dichloroplatinum(II) tetrakis(N,N'
      dimethylformamide) solvate and tetrakis(2-amino-5-methyl-1,3,4-thiadiazole
      N4)platinum(II) hexachloroplatinate(IV) bis(N,N'-dimethylformamide) solvate.
AB  - The structures of the title compounds,
      [PtCl(2)(C(7)H(5)N(3)O(2)S)(2)].4C(3)H(7)NO, (I), and
      [Pt(C(3)H(5)N(3)S)(4)][PtCl(6)].2C(3)H(7)NO, (II), respectively, comprise square
      planar Pt(II) centres. In the cation and anion of (II), the Pt atoms lie on
      independent inversion centres. For (I), the metal atom is N-bonded to two trans
      organic ligands and also bonded to two Cl atoms, whereas in (II), the Pt atom is
      N-bonded to four organic ligands, the charge being balanced by the presence of an
      additional [PtCl(6)](2-) species (from the starting material). Both structures
      contain dimethylformamide solvate molecules, four in the asymmetric unit of (I)
      and one in (II), which are involved in the hydrogen-bonding network via N-H.X and
      C-H.X associations.

PMID- 11588364
TI  - Dichlorobis(4-methylpentan-2-onato-C4,O)tin(IV) and bis(4-methylpentan-2-onato
      C4,O)(2-thioxo-1,3-dithiole-4,5-dithiolato-S,S')tin(IV) at 150 K.
AB  - The structures of the ketotins determined here, [SnCl(2)(C(6)H(11)O)(2)] and
      [Sn(C(3)S(5))(C(6)H(11)O)(2)], respectively, along with that previously reported
      for [MeC(O)CH(2)CMe(2)](2)SnI(2), are compared with the structures of the
      analogous estertins [MeOC(O)CH(2)CH(2)](2)SnX(2). Pairwise comparison of the mean
      ketotin [estertin] Sn-X and Sn-O distances as Sn-X 2.4422 (4) [2.4054 (7) A],
      2.4970 (4) [2.471 (2) A] and 2.8463 (4) [2.7788 (8) A] and Sn-O 2.4926 (12)
      [2.528 (1) A], 2.6110 (11) [2.629 (7) A] and 2.435 (3) [2.525 (4) A] (for X = Cl,
      S and I, respectively) clearly demonstrates the superior donor ability of the
      ketotin O atom in chelate formation.

PMID- 11588363
TI  - trans-Dichlorotetrakis(4-methylpyrimidine-N1)ruthenium(II).
AB  - The title compound, trans-[Ru(II)Cl(2)(N(1)-mepym)(4)] (mepym is 4
      methylpyrimidine, C(5)H(6)N(2)), obtained from the reaction of trans,cis,cis
      [Ru(II)Cl(2)(N(1)-mepym)(2)(SbPh(3))(2)] (Ph is phenyl) with excess mepym in
      ethanol, has fourfold crystallographic symmetry and has the four pyrimidine bases
      coordinated through N(1) and arranged in a propeller-like orientation. The Ru-N
      and Ru-Cl bond distances are 2.082 (2) and 2.400 (4) A, respectively. The methyl
      group, and the N(3) and Cl atoms are involved in intermolecular C-H...N and C
      H...Cl hydrogen-bond interactions.

PMID- 11588365
TI  - The first example of a silver-manganese-rhenium cluster complex: heptacarbonyl
      1kappa3C,2kappa4C-mu-dicyclohexylphosphido-1:2kappa2P-bis(triphenylphosphine)
      1kappaP,3kappaP-triangulo-manganeserheniumsilver with disordered solvent.
AB  - The title compound, [ReMnAg(C(12)H(22)P)(C(18)H(15)P)(2)(CO)(7)], is the first
      crystallographically characterized silver-manganese-rhenium cluster. Due to
      intramolecular steric repulsion, the central AgMnRe(mu-P) ring deviates greatly
      from planarity. Metal-metal distances are Mn-Re 3.1712 (8), Ag-Mn 2.7367 (8) and
      Ag-Re 2.8485 (6) A.

PMID- 11588367
TI  - Tetrakis(mu-2,3-dimethoxybenzoato)bis[(2,2'-bipyridine)(2,3
      dimethoxybenzoato)lanthanum(III)].
AB  - The title compound, tetrakis(mu-2,3-dimethoxybenzoato)
      kappa(4)O:O';kappa(6)O,O':O'-bis[(2,2'-bipyridine-N,N')(2,3-dimethoxybenzoato
      O,O')lanthanum(III)], [La(2)(2,3-DMOBA)(6)(2,2'-bpy)(2)], where 2,3-DMOBA is 2,3
      dimethoxybenzoate (C(9)H(9)O(4)) and 2,2'-bpy is 2,2'-bipyridine (C(10)H(8)N(2)),
      is a dimer with a centre of inversion between the La atoms bridged by four
      carboxylate ligands. The central La atom is ennea-coordinated and has a distorted
      monocapped square-antiprism geometry.

PMID- 11588366
TI  - Chloro(3,6,13,16-tetraethyl-2,7,12,17-tetramethylporphycenato-kappa4N)iron(III)
      chloroform solvate.
AB  - The X-ray crystallographic analysis of the title complex, chloro[3,10,13,20
      tetraethyl-4,9,14,19
      tetramethylpentacyclo[16.2.1.1(2,5).1(8,11).1(12,15)]tetracosa
      2,4,6,8(23),9,12,14,16,18(21),19-decaene]iron(III) chloroform solvate,
      [Fe(C(33)H(37)N(4))Cl].CHCl(3), reveals a twisted macrocyclic framework with a
      slightly distorted rectangular pyramidal core, where the deviation of the central
      Fe(III) atom from the least-squares plane of the C(20)N(4) core is 0.594 (1) A.
      Some important bond distances are as follows: Fe-N 2.019 (3), 2.026 (3), 2.028
      (3) and 2.034 (3) A; Fe-Cl 2.232 (1) A.

PMID- 11588368
TI  - A layered tin(II) phosphonate, [Sn(C6H5O3P)]n.
AB  - Poly[tin(II)-mu-phenylphosphonato], [Sn(C(6)H(5)O(3)P)](n), was synthesized
      solvothermally at 423 K and crystallized in the monoclinic system, space group
      Cc. The inorganic layers consist of alternating pyramidal Sn and tetrahedral P
      centers, joined by doubly bridging O atoms. The corner-sharing SnO(3) and
      PO(3)C(6)H(5) polyhedra define a corrugated layer of six-membered rings. The
      layers are connected along the unique b axis by interdigitated phenyl rings of
      the phenylphosphonate groups.

PMID- 11588369
TI  - Cis- and trans-influences in [PtCl2(SPh2)2].
AB  - Both cis- and trans-dichlorobis(diphenyl sulfide)platinum(II),
      [PtCl(2)(C(12)H(10)S)(2)], crystallize as mononuclear pseudo-square-planar
      complexes. In the cis compound, the Pt-Cl distances are 2.295 (2) and 2.319 (2)
      A, and the Pt-S distances are 2.280 (2) and 2.283 (2) A. In the trans compound,
      Pt is located on a centre of inversion and the Pt-Cl and Pt-S distances are
      2.2786 (15) and 2.3002 (12) A, respectively.

PMID- 11588370
TI  - Bis(2,4,7-trimethylindenyl)cobalt(II) and rac-2,2',4,4',7,7'-hexamethyl-1,1'
      biindene.
AB  - The crystal and molecular structures of bis(eta(5)-2,4,7
      trimethylindenyl)cobalt(II), [Co(C(12)H(13))(2)], (I), and rac-2,2',4,4',7,7'
      hexamethyl-1,1'-biindene, C(24)H(26), (II), are reported. In the crystal
      structure of (I), the Co atom lies on an inversion centre and the structure
      represents the first example of a bis(indenyl)cobalt complex exhibiting an
      eclipsed indenyl conformation. The (1R,1'R) and (1S,1'S) enantiomers of the three
      possible stereoisomers of (II), which form as by-products in the synthesis of
      (I), cocrystallize in the monoclinic space group P2(1)/c. In the unit cell of
      (II), alternating (1R,1'R) and (1S,1'S) enantiomers pack in non-bonded rows along
      the a axis, with the planes of the indenyl groups parallel to each other and
      separated by 3.62 and 3.69 A.

PMID- 11588371
TI  - Hydrogen bonding in bis(triphenylphosphine-P)iminium hydrogensulfate chloroform
      solvate.
AB  - The title compound, C(36)H(30)NP(2)(+).HSO(4)(-).CHCl(3), consists of discrete
      ions and well separated chloroform solvate molecules. The central feature of the
      structure is O-H...O hydrogen bonding between two hydrogensulfate ions related by
      a crystallographic inversion centre. The chloroform solvate molecule takes part
      in a well defined C-H...O hydrogen bond.

PMID- 11588372
TI  - 17-Oxo-16-(2-pyridylmethylene)androst-5-en-3beta-ol monohydrate.
AB  - The title compound, C(25)H(31)NO(2).H(2)O, has the outer two six-membered rings
      in chair conformations, while the central ring is in an 8beta,9alpha-half-chair
      conformation. The five-membered ring adopts a 13,14-half-chair conformation. The
      pyridylmethylene moiety has an E configuration with respect to the carbonyl group
      at position 17. The structure is stabilized by intermolecular O-H...N and O-H...O
      hydrogen bonds.

PMID- 11588373
TI  - Host-guest-like thiamine-anion complexation in thiaminium bis(tetrafluoroborate).
AB  - In the title compound, 3-[(4-amino-2-methyl-5-pyrimidin-1-io)methyl]-5-(2
      hydroxyethyl)-4-methylthiazolium(2+) bis(tetrafluoroborate),
      C(12)H(18)N(4)OS(2+).2BF(4)(-), the divalent thiamine cation (in the F
      conformation) is associated with BF(4)(-) anions via two characteristic bridging
      interactions between the thiazolium and pyrimidinium rings, i.e. C-H...BF(4)(
      )...pyrimidinium and N-H...BF(4)(-)...thiazolium interactions. Thiamine molecules
      are linked by N-H...O hydrogen bonds to form a helical chain structure.

PMID- 11588374
TI  - Two-component molecular crystals from N-heteroaromatics and nitrobenzoic acids.
AB  - Five two-component molecular crystals, benzimidazolium 3-nitrobenzoate,
      C(7)H(7)N(2)(+).C(7)H(4)NO(4)(-), (I), benzimidazolium 4-nitrobenzoate,
      C(7)H(7)N(2)(+).C(7)H(4)NO(4)(-), (II), 1H-benzotriazole-3-nitrobenzoic acid
      (1/1), C(6)H(5)N(3).C(7)H(5)NO(4), (III), imidazolium 3-nitrobenzoate,
      C(3)H(5)N(2)(+).C(7)H(4)NO(4)(-), (IV), and imidazolium 4-nitrobenzoate,
      C(3)H(5)N(2)(+).C(7)H(4)NO(4)(-), (V), were prepared with the aim of making
      chiral crystals. Only (I) crystallizes in a chiral space group. The molecules of
      (I) and (II) are linked by hydrogen bonds to form 2(1) spiral chains. In (III),
      (IV) and (V), macrocyclic structures are formed from two acid and two base
      components, by an alternate arrangement of the acid and base moieties.

PMID- 11588376
TI  - (-)-Dioxosantadienic acid: hydrogen-bonding patterns in a bicyclic
      sesquiterpenoid keto acid and its monohydrate.
AB  - The anhydrous form, (I), of the title compound, (-)-2-(1,2,3,4,4a,7-hexahydro
      4a,8-dimethyl-1,7-dioxo-2-naphthyl)propionic acid, C(15)H(18)O(4), derived from a
      naturally occurring sesquiterpenoid, has two molecules in the asymmetric unit,
      (I) and (I'), differing in the conformations of the saturated ring and the
      carboxyl group. The compound aggregates as carboxyl-to-ketone hydrogen-bonding
      catemers [O.O = 2.776 (3) and 2.775 (3) A]. Two crystallographically independent
      sets of single-strand hydrogen-bonding helices with opposite end-to-end
      orientation pass through the cell in the b direction, one consisting exclusively
      of molecules of (I) and the other entirely of (I'). Three C-H.O=C close contacts
      are found in (I). The monohydrate, C(15)H(18)O(4).H(2)O, (II), with two molecules
      of (I) plus two water molecules in its asymmetric unit, forms a complex three
      dimensional hydrogen-bonding network including acid-to-water, water-to-acid,
      water-to-ketone, water-to-water and acid-to-acid hydrogen bonds, plus three C
      H.O=C close contacts. In both (I) and (II), only the ketone remote from the acid
      is involved in hydrogen bonding.

PMID- 11588375
TI  - 3-Methyl 5-isopropyl 2-methoxyiminomethyl-6-methyl-4-(3-nitrophenyl)-1,4
      dihydropyridine-3,5-dicarboxylate.
AB  - The crystal structure of the title compound, C(20)H(23)N(3)O(7), consists of
      relatively isolated molecules. The substituted 1,4-dihydropyridine ring adopts a
      flattened boat conformation. Both ester groups, at positions 3 and 5, have
      cis,cis geometry. The phenyl ring is nearly planar and is approximately
      perpendicular to the 1,4-dihydropyridine ring (dihedral angle 87.70 degrees ).

PMID- 11588377
TI  - (1S)-(Z)-2-benzyloxy-N-(3-methyl-1-butylidene)-1-phenylethylamine N-oxide.
AB  - The preparation and crystal structure of the title compound, C(20)H(25)NO(2), are
      described. The N atom substituent of the nitrone function adopts a conformation
      which minimizes the 1,3-allylic strain.

PMID- 11588378
TI  - Two isomorphous benzenesulfonamide crystal structures determined by
      intermolecular C-H...O, C-H...pi and C-H...Cl interactions.
AB  - The title compounds, N-[5-(4-chlorophenyl)furan-2-ylmethyl]-4-methyl-N-(prop-2
      ynyl)benzenesulfonamide, (Ia), and N-[5-(2-chlorophenyl)furan-2-ylmethyl]-4
      methyl-N-(prop-2-ynyl)benzenesulfonamide, (Ib), both C(21)H(18)ClNO(3)S, have
      isomorphous crystal structures. The crystal packing is mainly determined by
      intermolecular C-H...O and C-H...pi interactions. These interactions are very
      similar in (Ia) and (Ib). Additional intermolecular C-H...Cl interactions appear
      less important and are different in (Ia) and (Ib). The different positions of the
      Cl atoms result in small variations of the crystal packing of the two compounds.

PMID- 11588379
TI  - pi-Facial selectivities of diastereotopic ketones: p-bromobenzoates of 4-hetero-1
      decalinols.
AB  - The crystal structures of the p-bromobenzoates of cis-4-oxa-1-decalinyl
      (C(16)H(19)BrO(3)), trans-4-oxa-1-decalinyl (C(16)H(19)BrO(3)), N-benzyl-cis-4
      aza-1-decalinyl (C(23)H(26)BrNO(2)), N-benzyl-trans-4-aza-1-decalinyl
      (C(23)H(26)BrNO(2)) and trans-4-thia-1-decalinyl (C(16)H(19)BrO(2)S) (decalin is
      perhydronaphthalene) have been determined as part of a study directed at
      predicting and interpreting the pi-facial selectivities of diastereotopic ketones
      in reactions with nucleophiles. All five structures are composed of molecules
      that are separated by normal van der Waals distances. In all five structures, the
      heterocyclic and cyclohexyl rings adopt chair conformations, and the p
      bromobenzoate groups are planar.

PMID- 11588380
TI  - Two intermediates in the synthesis of decahydroisoquinolines with NMDA and AMPA
      receptor antagonist activity.
AB  - In 6-methyl-N-(4-nitrobenzoyl)-5,6-dihydropyridin-2(1H)-one, C(13)H(12)N(2)O(4),
      (I), the piperidone ring is in a distorted half-chair conformation. In 8-methoxy
      3-methyl-N-(4-nitrobenzoyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline-1,6-dione,
      C(18)H(20)N(2)O(6), (II), the heterocyclic ring is in a slightly distorted half
      boat conformation, while the other six-membered ring is in a distorted chair
      conformation. Compound (II) presents a strong intramolecular C-H...O hydrogen
      bond. In both (I) and (II), the molecules interact through C-H...O interactions.

PMID- 11588381
TI  - 1-(2-[4-[6-Hydroxy-2-(4-hydroxyphenyl)benzo[b]thiol-3
      ylcarbonyl]phenoxy]ethyl)piperidinium chloride.
AB  - The title compound, raloxifene hydrochloride, C(28)H(28)NO(4)S(+).-Cl(-), belongs
      to the benzothiophene class of antiosteoporotic drugs. In the molecular cation,
      the 2-phenol ring sustains a dihedral angle of 45.3 (1) degrees relative to the
      benzo[b]thiophene system. The benzo[b]thiophene and phenyl ring planes are
      twisted with respect to the carbonyl plane, with the smallest twist component
      occurring between the phenyl and carbonyl planes. The N atom bears the positive
      charge in the molecular cation and the piperidine ring adopts an almost perfect
      chair conformation. The Cl(-) anion is involved in the formation of N-H...Cl and
      O-H...Cl intermolecular hydrogen bonds, which lead to the formation of a layer of
      molecular cations.

PMID- 11588382
TI  - 6-Deoxyjacareubin.
AB  - The natural compound 5,10-dihydroxy-2,2-dimethylpyrano[3,2-b]xanthen-6(2H)-one (6
      deoxyjacareubin), C(18)H(14)O(5), was isolated from leaves of Vismia latifolia
      (Guttiferae family). The compound has four six-membered rings. The molecule has
      two planar benzenoid and one planar pyranoid ring, plus a pyranoid ring in a
      distorted chair conformation. The crystal is stabilized by one intra- and one
      intermolecular hydrogen bond.

PMID- 11588383
TI  - 3-O-acetyl-4-deoxy-4-iodo-beta-D-fructofuranosyl 2,3,6-tri-o-acetyl-4-chloro-4
      deoxy-alpha-D-glucopyranoside.
AB  - At 160 K, the glucopyranosyl ring of the title compound, C(20)H(28)ClIO(13), has
      a near-ideal (4)C(1) conformation and the fructofuranosyl ring has a twist
      (4)T(3) conformation. The two hydroxy groups are involved in intra- and
      intermolecular hydrogen bonds, with the latter interactions linking the molecules
      into infinite one-dimensional chains. The absolute configuration of the molecule
      has been determined.

PMID- 11588384
TI  - 5-Nitro-2-nitromethyl-2H-1,2,3,4-tetrazole.
AB  - The molecule of the title compound, C(2)H(2)N(6)O(4), consists of three planar
      fragments, namely a tetrazole ring, a nitromethyl group and a nitro group. The
      nitro group and the tetrazole cycle are arranged in the same plane, but the
      planar nitromethyl group is located nearly orthogonal to this plane. The
      molecules are packed in the crystal via van der Waals interactions.

PMID- 11588385
TI  - Ethyl 6-amino-2-methoxypyridine-3-carboxylate, interplay of molecular and
      supramolecular structure.
AB  - The title compound, C(9)H(12)N(2)O(3), crystallizes with two molecules in the
      asymmetric unit. There is extensive hydrogen bonding which results in the
      formation of a two-dimensional corrugated sheet. This supramolecular structure is
      determined by the formation of hydrogen-bonded chains resulting from the presence
      of a 6-amino group and an ethoxycarbonyl group as substituents on a pyridine ring
      in relative para positions which constitute a pi-electron 'push-pull' system.

PMID- 11588386
TI  - 1,3,5-Triiodo-2,4,6-trimethylbenzene at 293 K.
AB  - In the structure of triiodomesitylene (1,3,5-triiodo-2,4,6-trimethylbenzene),
      C(9)H(9)I(3), at 293 K, the benzene ring is found to be significantly distorted
      from ideal D(6h) symmetry; the average endocyclic angles facing the I atoms and
      the methyl groups are 123.8 (3) and 116.2 (3) degrees, respectively. The angle
      between the normal to the molecular plane and the normal to the (100) plane is
      5.1 degrees. No disorder was detected at 293 K. The thermal motion was
      investigated by a rigid-body motion tensor analysis. Intra- and intermolecular
      contacts are described and topological differences compared with the isomorphous
      compounds trichloromesitylene and tribromomesitylene are discussed.

PMID- 11588387
TI  - Polysulfonylamines. CXLV. N-diethylcarbamoyl-o-benzenedisulfonimide, a urea with
      non-planar geometry at nitrogen and an amide single bond.
AB  - The prominent features in the molecular structure of the title compound
      (alternative name: 2-diethylcarbamoyl-1,1,3,3-tetraoxo-1,3,2-benzodithiazole),
      C(11)H(14)N(2)O(5)S(2), arise in the urea moiety S(2)N-C(O)-N'C(2): the sum of
      the angles at N is 332.3 (1) degrees, the N-C(O)-N'C(2) unit is planar, and
      distances N-C(O) = 1.494 (3) A, N'-C(O) = 1.325 (2) A and C-O = 1.215 (2) A. The
      molecules are associated via five C-H...O hydrogen bonds to form layers parallel
      to the yz plane. This compound and its dimethyl homologue, which were synthesized
      by treating the silver salt of o-benzenedisulfonimide with carbamoyl chlorides,
      are prone to rapid hydrolysis at the weak N-C(O) bond. For both molecules, the
      rotational barrier about the partial N'-C(O) double bond is ca 50 kJ mol(-1) at
      250 K (from dynamic (1)H NMR experiments).

PMID- 11588389
TI  - Methyl (SR)-10-chloro-1,2,3,4,5,6-hexahydro-6-hydroxy-8-methoxy-1-methyl-1,9
      phenanthroline-6-carboxylate.
AB  - In the title compound, C(16)H(19)ClN(2)O(4), the pyridine ring is nearly planar,
      the piperidine ring is non-planar and the cyclohexane ring adopts a screw-boat
      conformation. The carboxylate group makes a dihedral angle of 80.9 (2) degrees
      with the least-squares plane through the cyclohexane ring.

PMID- 11588388
TI  - X-ray investigations of sulfur-containing fungicides. IV. 4'-[[Benzoyl(4
      chlorophenylhydrazono)methyl]sulfonyl]acetanilide and 4'-[[benzoyl(4
      methoxyphenylhydrazono)methyl]sulfonyl]acetanilide.
AB  - The conformations of the two approximately isomorphous structures 4'-[[benzoyl(4
      chlorophenylhydrazono)methyl]sulfonyl]acetanilide, C(22)H(18)ClN(3)O(4)S, and 4'
      [[benzoyl(4-methoxyphenylhydrazono)methyl]sulfonyl]acetanilide,
      C(23)H(21)N(3)O(5)S, are stabilized by resonance-assisted intramolecular hydrogen
      bonds linking the hydrazone moieties and sulfonyl groups. The stronger bond is
      observed in the former compound. The difference in electronic properties between
      the Cl atom and the methoxy group is too small to significantly alter the non
      bonding interactions of the sulfonyl and beta-carbonyl groups.

PMID- 11588391
TI  - Melaminium chloride hemihydrate.
AB  - The crystals of a new melaminium salt, 2,4,6-triamino-1,3,5-triazin-1-ium
      chloride hemihydrate, C(3)H(7)N(6)(+).Cl(-).0.5H(2)O, are built up from single
      protonated melaminium residues, chloride anions and water molecules. The
      protonated melaminium cations lie on a twofold axis, while the chloride anions
      and water molecule lie on the m plane. The melaminium residues are interconnected
      by N-H...N hydrogen bonds, forming chains parallel to the (001) plane. The chains
      of melaminium residues form a three-dimensional network through hydrogen-bond
      interactions with chloride anions and water molecules.

PMID- 11588390
TI  - 1,4-Methano-11a-methyl-4,4a,11,11a-tetrahydro-1H-benzo[b]fluoren-11-one.
AB  - The title compound, C(19)H(16)O, crystallizes with two molecules of opposite
      chirality in the asymmetric unit. In both molecules, the naphthalene and
      cyclopentanone moieties are individually planar. The two cyclopentane rings adopt
      envelope conformations, while the cyclohexane ring adopts a boat conformation.

PMID- 11588392
TI  - Cyclic lipoundecapeptide amphisin from Pseudomonas sp. strain DSS73.
AB  - The crystal structure of the lipoundecapeptide amphisin, presented here as the
      tetrahydrate, C(66)H(114)N(12)O(20).4H(2)O, originating from non-ribosomal
      biosynthesis by Pseudomonas sp. strain DSS73, has been solved to a resolution of
      0.65 A. The primary structure of amphisin is beta-hydroxydecanoyl-D-Leu-D-Asp-D
      allo-Thr-D-Leu-D-Leu-D-Ser-L-Leu-D-Gln-L-Leu-L-Ile-L-Asp (Leu is leucine, Asp is
      aspartic acid, Thr is threonine, Ser is serine, Gln is glutamine and Ile is
      isoleucine). The peptide is a lactone, linking Thr4 O(gamma) to the C-terminal.
      The stereochemistry of the beta-hydroxy acid is R. The peptide is a close
      analogue of the cyclic lipopeptides tensin and pholipeptin produced by
      Pseudomonas fluorescens. The structure of amphisin is mainly helical (3(10)
      helix), with the cyclic peptide wrapping around a hydrogen-bonded water molecule.
      This lipopeptide is amphiphilic and has biosurfactant and antifungal properties.

PMID- 11588393
TI  - 5,6-Diphenylthieno[2,3-d][1,3]dithiole-2-thione.
AB  - The title compound, C(17)H(10)S(4), has two independent molecules in the
      asymmetric unit. In both molecules, the fused heterocycle is almost planar and
      the phenyl groups make dihedral angles of 42.88 (9) and 52.79 (8) degrees with
      the fused heterocycle in one molecule, and angles of 40.62 (9) and 52.28 (8)
      degrees in the other. The crystal packing is governed by short intermolecular S.S
      interactions, the shortest contact being 3.333 (1) A.

PMID- 11588394
TI  - Multipoint estimation of identity-by-descent probabilities at arbitrary positions
      among marker loci on general pedigrees.
AB  - OBJECTIVES: To describe, implement, and test an efficient algorithm to obtain
      multipoint identity-by-descent (IBD) probabilities at arbitrary positions among
      marker loci for general pedigrees. Unlike existing programs, our algorithm can
      analyze data sets with large numbers of people and markers. The algorithm has
      been implemented in the SimWalk2 computer package. METHODS: Using a rigorous
      testing regimen containing five pedigrees of various sizes with realistic marker
      data, we compared several widely used IBD computation programs: Allegro, Aspex,
      GeneHunter, MapMaker/Sibs, Mendel, Sage, SimWalk2, and Solar. RESULTS: The
      testing revealed a few discrepancies, particularly on consanguineous pedigrees,
      but overall excellent results in the deterministic multipoint packages. SimWalk2
      was also found to be in good agreement with the deterministic multipoint
      programs, usually matching to two decimal places the kinship coefficient that
      ranges from 0 to 1. However, the packages based on single-point IBD estimation,
      while consistent with each other, often showed poor results, disagreeing with the
      multipoint kinship results by as much as 0.5. CONCLUSIONS: Our testing has
      clearly shown that multipoint IBD estimation is much better than single-point
      estimation. In addition, our testing has validated our algorithm for estimating
      IBD probabilities at arbitrary positions on general pedigrees.

PMID- 11588395
TI  - Combination of linkage evidence in complex inheritance.
AB  - The central problem of complex inheritance is to combine evidence from data that
      typically differ in markers, phenotypes, ascertainment, and other factors,
      without sacrificing the reliability that lods have given to linkage mapping for
      major loci. Here we evaluate 5 possible solutions on 200 replicates simulated in
      Genetic Analysis Workshop 10. Two methods differ from less efficient ones by
      distinguishing the tails of a normal distribution. Maximum likelihood scores
      (currently implemented only for the BETA model) and the approach of Self and
      Liang perform about as well as pooling samples, which is not feasible with
      heterogeneous data. With moderately heterogeneous data the Self and Liang method
      appears to be more efficient than maximum likelihood scores. Although
      improvements are being made in sample design and statistical analysis, the
      problem of combining linkage evidence from multiple data sets appears to have
      been solved. Allelic association presents different problems not yet addressed.

PMID- 11588396
TI  - Y chromosome binary markers to study the high prevalence of males in Sardinian
      centenarians and the genetic structure of the Sardinian population.
AB  - We have analyzed a sample of 40 centenarians and 116 young controls from
      Sardinia, with a set of new Y chromosome binary markers, to evaluate if Y
      chromosome genes are involved in the high prevalence of males among centenarian
      Sardinians (1/2 vs. 1/4 in other populations studied). The results indicate that
      none of the seven lineages that account for >97% of the Y chromosome diversity in
      Sardinia provide an advantage with respect to the extreme longevity. However, our
      results, although based on the male-specific Y chromosome polymorphisms, give a
      clear profile of the pattern of genetic variability in Sardinia. Indeed they
      indicate that the Sardinian population had two main founder populations that have
      evolved in isolation for at least the last 5,000 years. These findings set the
      stage for future studies on longevity and other complex traits in Sardinia.

PMID- 11588397
TI  - A tournament of linkage tests in complex inheritance.
AB  - The performance of some weakly parametric linkage tests in common use was
      compared on 200 replicates of oligogenic inheritance from Genetic Analysis
      Workshop 10. Each random sample for the quantitative trait was dichotomized at
      different thresholds and also selected through 2 affected sibs, generating 8
      combinations of sample and variable. The variance component program SOLAR
      performed best with a continuous trait, even in selected samples, when the
      population mean was used. The sib-pair program SIBPAL2 was best in most other
      cases when the phenotype product, population mean, and empirical estimates of
      pair correlations were used. The BETA program that introduced phenotype products
      was slightly more powerful than maximum likelihood scores under the null
      hypothesis and approached but did not exceed SIBPAL2 under its optimal
      conditions. Type I errors generally exceeded expectations from a chi(2) test, but
      were conservative with respect to bounds on lods. All methods can be improved by
      use of the population mean, empirical correlations, logistic representation for
      affection status, and correct lods for samples that favour the null hypothesis.
      It remains uncertain whether all information can be extracted by weakly
      parametric methods and whether correction for ascertainment bias demands a
      strongly parametric model. Performance on a standard set of simulated data is
      indispensable for recognising optimal methods.

PMID- 11588398
TI  - Case-control studies of genetic markers: power and sample size approximations for
      Armitage's test for trend.
AB  - The association of a candidate gene with disease can be efficiently evaluated by
      a case-control study in which allele frequencies are compared for diseased cases
      and unaffected controls. However, when the distribution of genotypes in the
      population deviates from Hardy-Weinberg proportions, the frequency of genotypes-
      rather than alleles--should be compared by the Armitage test for trend. We
      present formulas for power and sample size for studies that use Armitage's trend
      test. The formulas make no assumptions about Hardy-Weinberg equilibrium, but do
      assume random ascertainment of cases and controls, all of whom are independent of
      one another. We demonstrate the accuracy of the formulas by simulations.

PMID- 11588399
TI  - Genetic heterogeneity in five Italian regions: analysis of PAH mutations and
      minihaplotypes.
AB  - Molecular analysis of 289 chromosomes has been performed in a cohort of
      phenylketonuria (PKU) patients whose ancestors lived in five Italian regions,
      Calabria, Campania, Piemonte, Puglia/Basilicata and Sicilia.
      Phenylalaninehydroxylase (PAH) gene mutations and minihaplotypes (combinations of
      PAH gene STR and VNTR systems) have been determined for 78.5 and 64%,
      respectively, of the chromosomes studied. 21 different minihaplotypes and 24 PKU
      mutations were found. Heterogeneity tests carried out for the frequencies of
      mutations and minihaplotypes show that the distribution of eight mutations and
      four minihaplotypes is statistically heterogeneous in the five Italian regions.
      Although the evolutionary rate of microsatellites or the age of these mutations
      is difficult to estimate with accuracy, our findings taken together show a
      genetic stratification of the Italian population. These results rule out allelic
      homogeneity of PKU at the molecular level between regions of Italy, yet
      minihaplotype data may be of practical use for a multistep approach to PAH gene
      genotyping.

PMID- 11588401
TI  - Estimation of the heritability of latent variables which are included in a
      structural model for metabolic syndrome.
AB  - In a study looking for risk factors of atherosclerosis in families with combined
      hyperlipidemia and hypertension, clinical and biochemical data of 1,149 persons
      were analyzed to develop two hypothetical multivariate scores concerning the
      degree to which a patient is affected by the metabolic syndrome. The scores are
      based on a structural model for low-density cholesterol (LDL) and high-density
      cholesterol (HDL), triglycerides, uric acid, creatinine, glucose, insulin,
      systolic blood pressure and waist-to-hip ratio. Age, gender and body mass index
      were used for adjusting all variables. In segregation analyses of 42 pedigrees
      without using genotype information, estimations of the heritabilities and
      environmentally caused variance and covariance components were computed for the
      individual score values of the two latent factors. The first score shows a
      heritability of 42%; the environment component disappeared. The score mainly
      reflects the HDL, LDL and triglyceride levels. The second score shows a
      heritability of 16% with an environment component of 7%. It includes mainly
      insulin, uric acid and creatinine. In the search for genetic causes, both scores
      could be a basis for further phenotypic classification of the metabolic syndrome.

PMID- 11588400
TI  - Evidence for mtDNA admixture between the Finns and the Saami.
AB  - OBJECTIVES: The Finns, and to a more extreme extent the Saami, are genetic
      outliers in Europe. Despite the close geographical contact between these
      populations, no major contribution of Saami mtDNA haplotypes to the Finnish
      population has been detected. METHODS: To examine the extent of maternal gene
      flow from the Saami into Finnish populations, we determined the mtDNA variation
      in 403 persons living in four provinces in central and northern Finland. For all
      of these samples, we assessed the frequencies of mtDNA haplogroups and examined
      sequence variation in the hypervariable segment I (HVS-I). The resulting data
      were compared with published information for Saami populations. RESULTS: The
      frequencies of the mtDNA haplogroups differed between the populations of the four
      provinces, suggesting a distinction between northern and central Finland.
      Analysis of molecular variance suggested that the Saami deviated less from the
      population of northern Finland than from that of central Finland. Five HVS-I
      haplotypes, including that harboring the Saami motif and the Asian-specific
      haplogroup Z, were shared between the Finns and the Saami and allowed comparisons
      between the populations. Their frequency was highest in the Saami and decreased
      towards central Finland. CONCLUSIONS: The high frequency of certain mtDNA
      haplotypes considered to be Saami specific in the Finnish population suggests a
      genetic admixture, which appears to be more pronounced in northern Finland.
      Furthermore, the presence of haplogroup Z in the Finns and the Saami indicates
      that traces of Asian mtDNA genotypes have survived in the contemporary
      populations.

PMID- 11588402
TI  - Preferential inactivation of a dupX(q23 --> q27-28) chromosome in a girl with
      mental retardation and dysmorphy.
AB  - We report on an 18-year-old female with de novo tandem duplication Xq23-->Xq27
      28. The breakpoints of the duplication segment have been mapped by FISH using a
      panel of locus specific YACs. Despite selective inactivation of the aberrant X
      chromosome, proven by a combination of molecular and cytogenetic studies, the
      patient exhibits mental retardation, dysmorphic features and short stature.
      Possible mechanisms explaining this unexpected finding are discussed.

PMID- 11588403
TI  - Low-dose combination therapy: why include a diuretic?

PMID- 11588404
TI  - Comments on medical research and the publication of scientific papers.

PMID- 11588405
TI  - Health care improvement and cost reduction opportunities in hypertensive Medicaid
      beneficiaries.
AB  - Hypertension and its complications are more frequent and occur about a decade
      earlier in life among high-risk groups, especially in the Southeast. Moreover,
      socioeconomic status is inversely related to hypertension and cardiovascular
      complications. Low-income, young and middle-aged adults living in the Southeast
      may be at especially high risk. Data on inpatient admissions among hypertensive
      Medicaid beneficiaries living in this region may provide insights on the burden
      of hypertension-related disease and on opportunities for successful intervention.
      A study of hospitalization rates and costs among 44,440 hypertensive Medicaid
      beneficiaries in South Carolina from 1993-1996 showed that 16,883 (38%) were
      continuously enrolled in Medicaid. Of this group, 63% were African American and
      74% were women. Among the continuously enrolled patients, 7637, or about 45%,
      were hospitalized during the 4-year period. These 7637 individuals accounted for
      20,698 hospital admissions, i.e., 2.7 admissions per person, over the 4-year
      interval. Nearly two thirds of the hospitalizations included a cardiovascular or
      renal diagnosis. Hospital claims paid reached nearly $90 million for the 7637
      hypertensive Medicaid recipients during the 4-year period. Among patients
      discharged from the hospital with congestive heart failure, 33% filled a
      prescription for an angiotensin-converting enzyme inhibitor within 90 days; 13%
      of patients discharged with an acute myocardial infarction filled a prescription
      for a beta blocker within 90 days. The data confirm that hypertensive Medicaid
      beneficiaries in the Southeast are hospitalized at high rates. Cardiovascular and
      renal morbidity account for the majority of the inpatient admissions. The
      findings suggest that the application of evidence-based guidelines would improve
      health, avoid cost, and reduce racial disparities in health outcomes.

PMID- 11588406
TI  - Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the
      control of essential hypertension.
AB  - In a multicenter, randomized, double-blind trial, the authors compared the
      antihypertensive efficacy of once-daily treatment with the new angiotensin II
      type 1 receptor blocker (ARB) olmesartan (20 mg) with recommended starting doses
      of losartan (50 mg), valsartan (80 mg), and irbesartan (150 mg) in 588 patients
      with a cuff diastolic blood pressure (DBP) of greater than or equal to 100 and
      less than or equal to 115 mm Hg and a mean daytime DBP of greater than or equal
      to 90 mm Hg and less than 120 mm Hg, as measured by ambulatory blood pressure
      monitoring. Cuff and ambulatory blood pressures were monitored at baseline and
      after 8 weeks of treatment. All groups were predominantly white and approximately
      62% male, and their mean age was approximately 52 years. In all groups, mean
      baseline DBP and systolic blood pressure (SBP) were approximately 104 and 157 mm
      Hg, respectively. The reduction of sitting cuff DBP with olmesartan (11.5 mm Hg),
      the primary efficacy variable of this study, was significantly greater than with
      losartan, valsartan, and irbesartan (8.2, 7.9, and 9.9 mm Hg, respectively).
      Reductions of cuff SBP with the four ARBs ranged from 8.4-11.3 mm Hg and were not
      significantly different. The reduction in mean 24-hour DBP with olmesartan (8.5
      mm Hg) was significantly greater than reductions with losartan and valsartan (6.2
      and 5.6 mm Hg, respectively) and showed a trend toward significance when compared
      to the reduction in DBP with irbesartan (7.4 mm Hg; p=0.087). The reduction in
      mean 24-hour SBP with olmesartan (12.5 mm Hg) was significantly greater than the
      reductions with losartan and valsartan (9.0 and 8.1 mm Hg, respectively) and
      equivalent to the reduction with irbesartan (11.3 mm Hg). All drugs were well
      tolerated. The authors conclude that olmesartan, at its starting dose, is more
      effective than the starting doses of the other ARBs tested in reducing cuff DBP
      in patients with essential hypertension.

PMID- 11588407
TI  - Analyzing the national cholesterol education program adult treatment panel III
      report: is new better?

PMID- 11588408
TI  - Obstructive sleep apnea and hypertension: from correlative to causative
      relationship.
AB  - Sleep-disordered breathing, manifested by repetitive episodes of partial or
      complete cessation of breathing during sleep associated with brief arousal and
      autonomic activation, is estimated to affect as many as 4% of adult men and 2% of
      adult women. Studies conducted during the 1980s revealed a strong association
      between sleep-disordered breathing and hypertension. The results of these early
      studies, which relied on relatively small samples of patients, have been
      confirmed in recent years by large-scale epidemiologic studies that are
      controlled for all possible confounding factors. This paper reviews the evidence
      suggesting a causative relationship between hypertension and disordered breathing
      in sleep. The authors discuss the possible underlying mechanisms of the two
      entities and address the clinical implications of this relationship. They
      conclude by recommending a proactive approach to the diagnosis of breathing
      disorders in sleep, in order to prevent the cardiovascular sequelae of this
      syndrome.

PMID- 11588409
TI  - Advances in antihypertensive combination therapy: benefits of low-dose thiazide
      diuretics in conjunction with omapatrilat, a vasopeptidase inhibitor.
AB  - The preferred initial agents for the treatment of high blood pressure are low
      dose thiazide diuretics, beta blockers, calcium antagonists, and angiotensin
      converting enzyme (ACE) inhibitors. In high-risk patients, including those with
      diabetes, renal insufficiency, left ventricular dysfunction, and atherosclerosis,
      ACE inhibitors may have specific benefit in reducing cardiovascular morbidity and
      mortality. Omapatrilat, the prototypical vasopeptidase inhibitor, inhibits not
      only ACE but also neutral endopeptidase. Like conventional ACE inhibitors,
      omapatrilat causes extracellular volume reduction and vasodilatation; moreover,
      it increases levels of atrial and brain natriuretic peptides and bradykinin.
      Effective blood pressure control, especially in the high-risk patient, usually
      necessitates combination therapy. A recent study randomized 274 subjects with
      mild to severe hypertension (stages 1-3 diastolic blood pressure elevation) and
      confirmed the benefits of omapatrilat combined with hydrochlorothiazide in
      patients not controlled on hydrochlorothiazide alone. The frequencies of adverse
      events, serious adverse events, and discontinuation attributed to adverse events
      were similar for omapatrilat and placebo. Furthermore, there were no clinically
      significant changes in serum creatinine, potassium, or other laboratory
      parameters. Adding omapatrilat to the background of hydrochlorothiazide treatment
      produced statistically significant additional reductions in trough diastolic and
      systolic blood pressures at weeks 4 and 8.

PMID- 11588410
TI  - Do blacks with ventricular dysfunction benefit from ACE inhibitor therapy?

PMID- 11588411
TI  - Effects of stress and behavioral interventions in hypertension--the effects of
      smoking and nicotine replacement therapy on blood pressure.

PMID- 11588412
TI  - Current concepts of pharmacotherapy in hypertension: combination calcium channel
      blocker therapy in the treatment of hypertension.
AB  - Effective control of blood pressure is usually achieved only with the use of two
      or more antihypertensive medications. The treatment options for hypertension are
      numerous, and the number of possible combinations large. The selection of a
      specific combination drug regimen has often been linked to the perceived need for
      diuretic therapy as first- or second-step therapy; thus, the popularity of such
      drug combinations as an angiotensin-converting enzyme (ACE) inhibitor/diuretic,
      an angiotensin-receptor blocker/diuretic, or a beta blocker/diuretic. Rational
      alternatives exist, including an ACE inhibitor/calcium channel blocker (CCB) or a
      dihydropyridine CCB/b blocker combination. Traditionally, recommendations have
      advised against the use of combination therapy with two drugs from the same
      therapeutic class. However, because of the different binding and pharmacologic
      characteristics of CCBs, a rationale exists for combining different agents in
      this class in the management of hypertension and/or symptomatic coronary artery
      disease. In the treatment of either hypertension or angina, combination CCB
      therapy can prove uniquely successful.

PMID- 11588413
TI  - Common questions and answers in the management of hypertension. Sleep apnea in
      hypertensives: three simple questions.

PMID- 11588415
TI  - Mechanisms of corneal graft rejection: the sixth annual Thygeson Lecture,
      presented at the Ocular Microbiology and Immunology Group meeting, October 21,
      2000.
AB  - The history of corneal transplantation reaches back over 150 years. Kissam
      performed one of the first penetrating keratoplasties when he transplanted a pig
      cornea onto a human in 1838. Only two interrupted sutures were used, and the
      surgery was performed without anesthesia! In retrospect, no one would be
      surprised to learn that the porcine corneal xenograft was rejected. Thirty years
      later, May transplanted rabbit corneal grafts to humans, but concluded that the
      failures in the first 24 attempts were the result of "imperfect technique and the
      inability to keep the eyes properly bandaged." The first documented report of a
      successful penetrating keratoplasty in a human subject was performed by Zirm in
      1905. As we enter the new millennium, corneal transplantation remains the oldest,
      most common, and, arguably, the most successful form of solid tissue
      transplantation. In the United States alone, approximately 36,000 corneal
      transplants are performed each year. The success rate for corneal transplants is
      in excess of 90% in uncomplicated cases, even though HLA tissue typing is not
      performed and systemic immunosuppressive drugs are not administered. In spite of
      this extraordinary success, immune rejection remains the leading cause of corneal
      graft failure. Many inferences about the immunobiology of corneal graft rejection
      have been based on clinical observations; however, confirmation of these
      hypotheses requires prospective studies under controlled settings. The prudent
      use of animal models has fostered analytic studies on the immunobiology of
      corneal allografts without the complicating and confounding effects of topical
      steroids that are typically used on most keratoplasty patients. Although animal
      models of penetrating keratoplasty have been in use for almost a half-century,
      until recently, progress in understanding the immune mechanisms of corneal graft
      rejection has been slow. However, the widespread use of rodent models of
      orthotopic corneal transplantation has shed new light on the pathogenesis of
      corneal graft rejection.

PMID- 11588416
TI  - Cancer transmission through corneal transplantation.
AB  - PURPOSE: A retrospective study to demonstrate the safety of corneas from donors
      affected by systemic malignancies in a view of keratoplasty. METHODS: Using the
      data of the cancer registry department in a district of 500,000 residents, we
      analyzed retrospectively 143 patients followed up in the same region and
      transplanted between 1987 and 1995. We compared the incidence of cancer in
      recipients of cornea coming from donors with malignancies with recipients of
      cornea from donors without malignancies. The rate of cancer in this population
      was also compared with the incidence of cancer in the general population at the
      same age. RESULTS: Eleven patients (7%) were excluded from the study, eight of
      them for the presence of cancer in their medical history before surgery and the
      three others because of lack of information about their follow-up after surgery.
      Forty patients received corneas from cancerous donors and 103 from donors without
      cancer. Six patients developed malignancies between 1 and 4 years after
      transplantation, and only one of them received a cornea from a donor with a
      systemic malignancy. This recipient developed a different type of cancer from
      that of the donor. The five other patients received corneas from donors without
      systemic malignancies. By comparing theses results, there was no relationship
      between the occurrence of malignancies and transplantation of corneas from
      cancerous donors (relative risk = 0.49, 95% confidence interval = 0.01-13.62).
      CONCLUSION: There was no increased incidence of cancer in our patient population
      compared with reference population. Based on this study, there is no statistical
      or clinical evidence to suggest the transmission of cancer from donors with
      malignancies via corneal transplantation, according to the accepted criteria of
      donor selection.

PMID- 11588417
TI  - Comparison of Chen Medium and Optisol-GS for human corneal preservation at 4
      degrees C: results of transplantation.
AB  - PURPOSE: To compare results after transplantation of donor corneas stored in Chen
      Medium (containing beta-hydroxybutyrate without sodium bicarbonate or chondroitin
      sulfate) to corneas stored in Optisol-GS medium (containing sodium bicarbonate
      and 2.5% chondroitin sulfate). METHODS: We performed 32 consecutive penetrating
      keratoplasties with donor corneas stored at 4 degrees C in either Chen Medium or
      Optisol-GS by random assignment. Corneal thickness measurements were made at 1
      day, 1 week, 3 weeks, 2 months, and 1 year postkeratoplasty. Specular microscopic
      images of the donor endothelium were obtained at the beginning of storage and 2
      months and 1 year postkeratoplasty. The percentage of intact epithelium 1 day
      after keratoplasty and the graft epithelialization time were estimated by the
      surgeons. Donor rim cultures were performed. RESULTS: No statistically
      significant differences in corneal thickness or endothelial cell loss between the
      corneas stored in the two media were found at any time, although differences of
      less than 12% cell loss or 0.09-mm thickness at 2 months or less than 25% cell
      loss or 0.10-mm thickness at 1 year could not be excluded with 90% certainty in
      this small series. The mean percentages of intact graft epithelium on day 1, 64%
      for Chen Medium and 65% for Optisol-GS, were not significantly different.
      Endothelial cell density 2 months postkeratoplasty was significantly decreased
      for corneas stored in both media. Endothelial cell loss at 2 months was directly
      correlated with storage time in both media. CONCLUSIONS: After keratoplasty, no
      statistically significant differences in corneal thickness, epithelial survival,
      and endothelial cell loss were found between corneas stored in Chen Medium and
      Optisol-GS. Endothelial cell loss at 2 months was significantly correlated with
      storage time in both media.

PMID- 11588418
TI  - Patient satisfaction after corneal transplantation.
AB  - PURPOSE: To determine the relationship between objective and subjective outcome
      measures and patient satisfaction after corneal transplantation. METHODS: Data
      were collected for 184 patients who underwent a corneal transplantation between 1
      and 5 years ago. Only patients with the diagnosis of bullous keratopathy,
      endothelial decompensation (or Fuchs dystrophy), nonherpetic keratitis, and
      keratoconus were included. Objective treatment outcome measures, such as clarity
      of the graft and visual acuity in the grafted eye, were collected prospectively.
      Visual acuity of the other eye was collected retrospectively by chart review.
      Subjective outcome measures were derived from a retrospective survey. In addition
      to assessment of patient satisfaction, the survey provided information regarding
      subjective outcome measures, such as visual functioning and quality of life.
      RESULTS: The response rate was 86%. Generally, patients indicated that they were
      satisfied with the results of the transplantation. Age was negatively related to
      satisfaction, with older patients being less satisfied. On average, patients with
      keratoconus were most satisfied. Subjective outcome measures explained 57% of the
      variance in patient satisfaction, whereas objective factors explained 12%.
      Receipt of patient education during treatment was the best predictor. Other
      important variables were quality of life and visual functioning. CONCLUSION: In
      general, corneal transplantation had a positive effect on objective and
      subjective outcome measures. Patient satisfaction was better predicted by
      subjective outcomes than by objective outcomes. Patient education, in particular,
      proved to be a crucial factor. Objective outcome measures appeared to have a more
      indirect influence on patient satisfaction.

PMID- 11588419
TI  - Corneal disease in patients with chronic renal insufficiency undergoing
      hemodialysis.
AB  - PURPOSE: To evaluate alterations of the corneal endothelium in patients
      undergoing hemodialysis for renal insufficiency. METHODS: Sixty-six patients
      undergoing hemodialysis received a complete ophthalmologic examination. The state
      of the endothelium was assessed using pachymetry and specular microscopy. The
      group of patients undergoing dialysis was divided according to the time of
      dialysis, aluminum, product of calcium and phosphate in blood, and parathyroid
      hormone to analyze the influence of these factors. The possible presence of iron
      and aluminum in the aqueous humor of patients who underwent and those who did not
      undergo hemodialysis was also estimated. RESULTS: Patients undergoing
      hemodialysis did not have significant corneal edema. Cell density was
      significantly lower in patients undergoing dialysis than in patients not
      undergoing dialysis; this reduction appeared to be associated with length of
      dialysis and was unrelated to serum aluminum and calcium levels. Patients
      undergoing dialysis did not have cell polymorphism or polymegethism, although
      there was a tendency toward increased polymegethism with length of dialysis.
      Aluminum and iron were not increased in the aqueous humor of patients undergoing
      dialysis. CONCLUSIONS: The alteration of the endothelium that we found is not
      related to the elements studied. It is possibly the result of another product
      dissolved in the anterior chamber or to the alterations of the anterior segment
      that these patients are known to have.

PMID- 11588420
TI  - Measures for preventing recurrence after pterygium surgery.
AB  - PURPOSE: To introduce an improved technique of pterygium surgery and to compare
      postoperative results between this technique and previous techniques. METHODS: In
      a retrospective survey, the records of 216 consecutive eyes with primary
      pterygium that underwent surgery by three different techniques were reviewed. The
      new technique (mini-flap technique) involves making a small excision of the
      pterygium body, removing the pterygium head by scraping with forceps, applying
      mitomycin C (MMC), and performing a small conjunctival transposition flap. The
      previous technique (large-flap technique II) involved making a large excision in
      the pterygium body, removing the pterygium head with a knife, applying MMC, and
      performing a large transposition flap. Large-flap technique I is the same as
      large-flap technique II except for the use of intraoperative MMC. The recurrence
      rate of each technique was estimated by the Kaplan-Meier life table analysis.
      RESULTS: The recurrence rates estimated at 1 year after surgery were 15.5% in
      large-flap technique I, 4.2% in large-flap technique II, and 0% in the mini-flap
      technique. Large-flap technique II or the mini-flap technique had significantly
      lower recurrence rates compared with large-flap technique I ( p = 0.02 and p <
      0.01, respectively). The mini-flap technique had a significantly lower incidence
      of conjunctival scarring or granuloma compared with large-flap technique I and
      large-flap technique II ( p = 0.05 and p = 0.03, respectively.) CONCLUSIONS: The
      mini-flap technique was useful for preventing recurrence and was technically
      easier and induced fewer postoperative complications than large-flap techniques I
      and II.

PMID- 11588421
TI  - Pterygium in young members of one family.
AB  - PURPOSE: To report a family with aggressive, early-onset pterygium. METHODS: We
      examined all living relatives (with one exception) of a Saudi Arabian family and
      found three members with pterygium (onset occurred when the patients were at
      early 20s, 6, and 4 years of age). RESULTS: Multiple attempts at surgical
      removal, even in conjunction with application of topical mitomycin C and use of
      conjunctival autograft, failed to prevent recurrent pterygium, which advanced
      across the visual axis and produced profound visual disability in the three
      cases. CONCLUSION: Contrary to previously published reports of familial
      pterygium, two of the three cases had childhood age at onset and all three had an
      aggressive clinical course after the onset of recurrent pterygium after surgical
      resection; genetic identification may be beneficial.

PMID- 11588422
TI  - Scanning-slit and specular microscopic pachymetry in comparison with ultrasonic
      determination of corneal thickness.
AB  - PURPOSE: To determine the central corneal thickness values in healthy eyes with
      the recently developed Orbscan scanning-slit system, contact and noncontact
      specular microscopic pachymetry and compare the results to conventional
      ultrasonic pachymetry. METHODS: In the following sequence, Orbscan, Topcon SP
      2000P noncontact specular microscope, AL-1000 ultrasound, and Tomey contact
      specular microscope were used to record thickness values. Thirty-four healthy
      right corneas of 34 healthy subjects were investigated. RESULTS: Orbscan
      pachymetry correlated significantly with ultrasound (r = 0.64, p < 0.001),
      contact (r = 0.45, p < 0.001), and noncontact specular microscopy (r = 0.72, p <
      0.001). Likewise, the Topcon SP-2000P noncontact specular microscopy pachymetry
      disclosed similar statistical results compared with ultrasound (r = 0.88, p <
      0.001), and contact specular microscopy pachymetry (r = 0.76, p < 0.001). The
      mean central corneal thickness results were significantly higher ( p < or = 0.01)
      than ultrasonic values (580 +/- 43 microm) using the contact specular microscope
      (640 +/- 43 microm) or Orbscan system (602 +/- 59 microm) but were significantly
      lower ( p < 0.001) using the noncontact specular microscope (547 +/- 49 microm).
      CONCLUSIONS: The results indicate that the devices tested cannot be simply used
      interchangeably. For long-term patient follow-up, one specific instrument is
      recommended. Recently developed pachymetry machines are especially helpful when
      additional corneal data such as thickness profile, elevation maps, anterior
      chamber depth, and endothelial morphology are required.

PMID- 11588423
TI  - Intracameral amphotericin B: initial experience in severe keratomycosis.
AB  - PURPOSE: Fungal keratitis is a significant cause of ocular morbidity in India.
      The most commonly implicated fungi are Aspergillus spp. Patients often present
      with hypopyon, which usually contains fungal elements. The treatment is difficult
      owing to poor intraocular penetration of most available antifungal agents. This
      study evaluated the results of intracameral injection of amphotericin B in
      natamycin resistant cases of severe keratomycosis. METHODS: Three patients of
      culture proven Aspergillus flavus corneal ulcer with hypopyon not responding to
      topical natamycin 5%, amphotericin B 0.15%, and oral itraconazole were
      administered intracameral amphotericin B. The first case received 7.5 microg in
      0.1 mL followed by two subsequent injections of 10 microg in 0.1 mL each, the
      second case received two injections of 10 microg in 0.1 mL, and the third patient
      received a single dose of 10 microg in 0.1 mL. Culture of the aqueous sample also
      grew A. flavus in all three cases. RESULTS: All three cases responded favorably,
      with the ulcer and hypopyon clearing completely. There was no clinical evidence
      of corneal or lenticular toxicity in any patient. CONCLUSIONS: Intracameral
      amphotericin B may be a useful modality in the treatment of severe keratomycosis
      not responding to topical natamycin. It ensures adequate drug delivery into the
      anterior chamber and may be especially useful to avoid surgical intervention in
      the acute stage of the disease.

PMID- 11588424
TI  - Amniotic membrane transplantation in infectious corneal ulcer.
AB  - PURPOSE: To evaluate the efficacy of amniotic membrane transplantation in the
      management of treated infectious corneal ulcer in which inflammatory reactions
      were responsible for corneal damage. METHOD: A prospective study of 21
      consecutive eyes (21 patients) was performed. Sufficient antibacterial,
      antifungal, or antiviral agents were applied to eradicate causative organisms
      before permanent or temporary amniotic membrane transplantation, or a combination
      of the two in few patients. The amniotic membrane was soaked in antiinfective
      agents before transplantation in all cases. RESULTS: After amniotic membrane
      transplantation, follow-up times ranged from 4 to 28 months (mean, 18 months).
      Clinical indications included Staphylococcus species (four cases), Pseudomonas
      species (five cases), Acanthamoeba species (three cases), fungus (two cases), and
      herpesvirus (seven cases). The corneal surface was healed successfully and
      recurrences of microbial infection were not noted in any case. Visual acuity was
      improved in cases that were nonscarring or after additional penetrating
      keratoplasty. CONCLUSION: Amniotic membrane transplantation seems to be a useful
      adjunctive surgical procedure for the management of infectious corneal ulcer by
      promoting wound healing and reducing inflammation.

PMID- 11588425
TI  - Compression sutures in the management of corneal transplant wound infections.
AB  - PURPOSE: To report the usefulness of compression sutures in the management of
      three cases of bacterial wound infections in corneal transplants. METHODS:
      Interventional case series. RESULTS: All three cases of wound dehiscence and
      perforation resulting from bacterial wound infections were successfully treated
      with placement of compression sutures with concurrent topical antibiotic
      treatment. CONCLUSION: The placement of compression sutures is a successful
      surgical technique to reestablish corneal transplant wound integrity compromised
      by infection.

PMID- 11588426
TI  - Transplantation of adult human corneal endothelium ex vivo: a morphologic study.
AB  - PURPOSE: To investigate the feasibility of transplanting untransformed human
      corneal endothelial cells as a treatment strategy and possible alternative for
      penetrating keratoplasty by growing donor cells in culture and then transplanting
      them to denuded Descemet's membrane of recipient corneas. METHODS: Corneas from
      adult donors (50-80 years old) were obtained from eye banks. To grow corneal
      endothelial cells, Descemet's membrane with associated cells was dissected from
      the stroma. Endothelial cells were released by ethylenediaminetetraacetic acid
      treatment, grown in medium containing multiple growth factors, and identified as
      being of endothelial origin by morphology and by reverse-transcription polymerase
      chain reaction for keratin 12 and collagen type VIII. In transplantation
      experiments, cultured cells were seeded onto denuded Descemet's membrane of a
      second donor cornea at 5 x 10(5) cells/mL. The recipient cornea was incubated in
      organ culture for as long as 2 weeks. The morphology and ultrastructure of the
      endothelium were evaluated 7 and 14 days after transplantation by transmission
      electron microscopy, and by immunolocalization of zonula occludins-1 (ZO-1).
      Endothelial cell density was calculated in transplants by counting ZO-1-stained
      cells. RESULTS: Corneal endothelial cells cultured from adult donors consistently
      grew well in culture medium. Cells were identified as corneal endothelium by
      characteristic morphology and messenger RNA expression. Morphologic and
      ultrastructural studies of corneas containing transplanted endothelial cells
      demonstrated that with time there was an increase in endothelial cell-Descemet's
      membrane adhesion, in the extent of cell-cell contacts and lateral
      interdigitation, and in formation of a single cell layer. ZO-1 staining revealed
      tight junction formation similar to that of corneas in vivo. Mean endothelial
      cell density in transplanted corneas was 1,895 cells/mm(2) (range, 1,503-2,159
      cells/mm(2) ). CONCLUSION: Untransformed adult human corneal endothelial cells
      can be efficiently and consistently cultured and transplanted onto denuded
      Descemet's membrane. Transplanted cells in organ culture exhibit morphologic
      characteristics and cell densities similar to corneal endothelial cells in vivo.
      These results provide evidence for the feasibility of developing methods for in
      vivo transplantation of untransformed corneal endothelial cells cultured from
      adult donor tissue.

PMID- 11588427
TI  - Expression of vascular endothelial growth factor and inducible nitric oxide
      synthase in pterygia.
AB  - PURPOSE: To evaluate the expression of vascular endothelial growth factor (VEGF)
      in pterygium and investigate the interrelationships between VEGF and nitric oxide
      (NO) in the development of pterygia. METHODS: Specimens of normal conjunctiva
      acquired incidentally to conjunctival transplantation during pterygium and
      strabismus surgery and the excised pterygium were used in this study.
      Cryopreserved tissue specimens consisting of normal conjunctiva and pterygium
      were used to study the expression of VEGF and inducible NO synthetase (iNOS),
      using immunohistochemistry. For confirmation of NOS activity, reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining was done.
      Enzyme-linked immunosorbent assay (ELISA) for detection and quantification of
      VEGF was performed. RESULTS: Expression of VEGF and iNOS was strongly revealed
      mainly in the epithelium of the head portions of pterygial specimens, although
      not in the epithelium of conjunctival ones. Pterygial epithelium was stained with
      NADPH diaphorase, confirming NOS activity. ELISA showed a greater amount of VEGF
      in pterygium (11.7 +/- 2.1 pg/mg) compared with normal conjunctiva (4 +/- 0.47
      pg/mg) ( p < 0.05). CONCLUSION: These data are the first to demonstrate that VEGF
      and NO may play an important role in the development of pterygium and to identify
      VEGF and NO in the epithelium of pterygium. We hypothesize that environmental
      stress, such as ultraviolet irradiation and local inflammation stimulate the
      elaboration of NO and VEGF, resulting in the conjunctival fibrovascular ingrowth
      characteristic of pterygium.

PMID- 11588428
TI  - Interleukin-8 concentrations in conjunctival epithelium brush cytology samples
      correlate with neutrophil, eosinophil infiltration, and corneal damage.
AB  - PURPOSE: To evaluate whether interleukin-8 (IL-8) and RANTES (regulated on
      activation, normal T-cell expressed and secreted) concentrations in the
      supernatants of conjunctival epithelial samples from patients with vernal
      keratoconjunctivitis (VKC) correlate with the number of infiltrating eosinophils
      or neutrophils and with the severity of corneal lesions. METHODS: Thirty-four
      patients with VKC, 5 patients with seasonal allergic conjunctivitis, and 10
      volunteers without allergic diseases were enrolled in this study. Conjunctival
      epithelial cells were collected by brush cytology and the number of inflammatory
      cells was counted. The chemokine expression in the cells was investigated by
      immunocytochemistry and the chemokine concentrations of the cell suspensions were
      measured by enzyme-linked immunosorbent assay. RESULTS: The percentages of
      eosinophils and neutrophils in cell suspensions from VKC patients with corneal
      erosion or ulcer were higher than those from subjects with clear corneas or
      superficial punctate keratopathy. IL-8 concentrations in the supernatant of
      samples correlated significantly with the percentages of neutrophils and
      eosinophils in paired cell suspensions. No correlation was observed between
      RANTES and the percentages of eosinophils. Positive staining for IL-8 was
      observed in the cytosol of conjunctival epithelial cells. CONCLUSION: IL-8 in the
      extracellular space of the conjunctival epithelium may play a role in the
      recruitment of neutrophils and possibly eosinophils and in the pathogenesis of
      corneal damage in severe allergic diseases.

PMID- 11588430
TI  - Ocular surface reconstruction in LOGIC syndrome by amniotic membrane
      transplantation.
AB  - PURPOSE: To determine whether preserved amniotic membrane can be used to
      reconstruct the ocular surface after excision of the invading granulation
      material typical of LOGIC syndrome (laryngeal and ocular granulation tissue in
      children from the Indian subcontinent). METHODS: Granulation tissue was dissected
      and excised from both eyes of a 10-year-old boy with LOGIC syndrome. This
      procedure was followed by coverage of the corneal, scleral, and subtarsal regions
      of each eye with amniotic membrane, which had been stored for 6 months at -70
      degrees C. RESULTS: Initial 2.5-month follow up demonstrated complete
      disappearance of granulation tissue. The fornices were patent, there was no
      recurrence of symblepharon, ocular inflammation was suppressed, and the patient
      reported markedly increased comfort. Both eyelids remained ptotic because of
      levator muscle atrophy secondary to many years of inability to open either eye.
      No residual scarring or evidence of granulation tissue was observed in that
      period. The 10-month follow up demonstrated limited recurrence, particularly
      where there was an intraoperative break in the amniotic membrane. CONCLUSIONS:
      After 24 operations to treat the ocular complications induced by LOGIC syndrome,
      amniotic membrane transplantation was the first effective treatment. In the early
      follow up period (2-3 months), there was complete cessation of the proliferation
      of granulation tissue and reepithelialization of the corneal surface. Longer
      follow up (10 months) demonstrated limited recurrence, which will require
      retreatment.

PMID- 11588429
TI  - Prolongation of corneal allograft survival using cyclosporine in a polylactide-co
      glycolide polymer.
AB  - PURPOSE: To test for prolongation of corneal transplant survival with
      cyclosporine in a polymer placed in the anterior chamber of corneal allograft
      recipients. METHODS: Wistar inbred rats with vascularized corneas were recipients
      of corneal allografts from Sprague-Dawley donor rats. Grafted rats were
      randomized into six groups: untreated control animals, cyclosporine-polymer
      anterior chamber recipients, cyclosporine-polymer subconjunctival recipients,
      cyclosporine-olive oil drop recipients, polymer-only anterior chamber recipients,
      and autografted Wistar rats. Grafts were examined by slit lamp every 3 days and
      the clinical condition scored. The cyclosporine concentration in the aqueous
      humor was assayed at 1, 2, and 4 weeks. At 2 and 4 weeks after transplantation,
      the eyes were collected for histopathologic evaluation of the grafts. RESULTS:
      The median survival time of untreated corneal allografts was 8.2 +/- 1.48 days
      for grafts treated with topical cyclosporine, 8.5 +/- 1.50 days for polymer-only
      anterior chamber implants, 10.6 +/- 1.90 days for 1% cyclosporine drops, 11.4 +/-
      2.50 days for grafts given subconjunctival cyclosporine-polymer, 17 +/- 3.05 days
      for grafts given cyclosporine-polymer implants in the anterior chamber, and more
      than 3 months in autografted rats. There was a statistically significant
      difference ( p < 0.05) between the survival time of the allografts in the animals
      treated with the cyclosporine-polymer in the anterior chamber compared with the
      other groups of graft recipients. Significantly higher concentrations of
      cyclosporine were found in the eyes given an anterior chamber implant of
      cyclosporine-polymer than in the other treatment groups or the untreated rats.
      The cyclosporine-polymer implants placed in the anterior chamber induced a
      transient inflammatory response in transplanted eyes. CONCLUSIONS: Cyclosporine
      polymer placed in the anterior chamber significantly prolongs corneal allograft
      survival in a high-risk corneal graft rejection. This intraocular delivery system
      may be a valuable adjunct for the suppression of immune graft rejection in high
      risk recipients of corneal transplants.

PMID- 11588431
TI  - Atypical presentation of Acanthamoeba keratitis.
AB  - PURPOSE: To present two cases of minimal pain Acanthamoeba keratitis to alert
      clinicians to remember Acanthamoeba when evaluating atypical cases of keratitis.
      METHODS: The histories of two cases were reviewed with attention to clinical
      presentation subjective complaints, treatment, and long-term outcome. RESULTS: In
      case 1, a 24-year-old man presented with decreased vision and an irritated
      feeling in his eye. He did not wear contact lenses. His initial diagnosis was
      adenoviral conjunctivitis. One month later, he was diagnosed with atypical herpes
      simplex keratitis and started on acyclovir. Two weeks later, he was referred to
      the Cornea Service. Further history revealed the patient to be a professional
      triathlete who trained by swimming in a fresh water pond. He was found to have an
      unusually high pain tolerance. Biopsy revealed Acanthamoeba. He was admitted for
      intensive therapy with neomycin, propamidine isethionate, and polyhexamethylene
      biguanide. Two years after diagnosis, he has best-corrected visual acuity of
      20/100. In case 2, a 28-year-old man with known herpes simplex keratitis
      presented with decreased vision. He was started on topical trifluridine. After 6
      weeks without improvement, he was referred for corneal evaluation. His eye always
      remained comfortable. Corneal sensation was markedly decreased. Further history
      revealed that he swam in fresh water. Biopsy was positive for Acanthamoeba. After
      1 year of therapy with polyhexamethylene biguanide and neomycin, visual acuity
      was 20/200, and the patient underwent a corneal transplant. CONCLUSION:
      Acanthamoeba keratitis must be considered in the differential diagnosis of
      keratitis, even without the classic presentation of severe pain and predisposing
      corneal trauma, including contact lens wear.

PMID- 11588432
TI  - Juvenile xanthogranuloma: concurrent involvement of skin and eye.
AB  - PURPOSE: To report a novel presentation of ocular involvement in juvenile
      xanthogranuloma (JXG). CASE REPORT: A 1-year-old boy with the concurrent skin and
      eye involvement of JXG is presented. The ocular problems included spontaneous
      hyphema, secondary glaucoma, and 360-degree involvement of the limbus, iris, and
      angle. RESULTS: To reduce the intraocular pressure (IOP), treatment was started
      with drops of timolol, betamethasone, and atropine and acetazolamide suspension.
      After 6 months of medical treatment, the skin lesions did not change, but the
      iris lesion enlarged without hyphema. The IOP in the right eye was controlled by
      the medications. CONCLUSION: Although JXG is an uncommon disease, it is one of
      the most important causes of spontaneous hyphema in children. Iris involvement,
      spontaneous hyphema, and secondary glaucoma are the most common ocular problems.
      Corneal involvement often is characterized by a yellowish protrusion of the
      limbus along with blood staining of recurrent hyphema and elevated IOP. In this
      report, we describe an unusual case of JXG with 360-degree limbus, iris, and
      angle involvement. To our knowledge, this is the first report in the medical
      literature of 360-degree limbus involvement in JXG.

PMID- 11588433
TI  - Retrocorneal membrane with Descemet's detachment.
AB  - PURPOSE: To describe a unique case of retrocorneal membrane with large Descemet's
      detachment. METHODS: Case report of a 65-year-old man reported intermittent
      cloudy vision in his left eye. The patient underwent serial ocular examinations
      and slit-lamp photography over 6 weeks. RESULTS: The patient had an inflammatory
      appearing membrane that covered 60% of the posterior cornea, with a subtotal
      Descemet's detachment. Vision was stable at 20/20, and the cornea remained clear.
      The patient was empirically treated with topical
      neomycin/polymyxin/dexamethasone, sodium chloride, and oral acyclovir, and his
      symptoms improved; however, the retrocorneal membrane persisted. CONCLUSION: This
      unusual clinical finding may represent reduplicated Descemet's membrane with
      partial Descemet's detachment secondary to occult deep herpes simplex keratitis.
      Other possibilities include spontaneous or traumatic Descemet's tear and
      detachment.

PMID- 11588434
TI  - An unusual case of fungal keratitis: Metarrhizium anisopliae.
AB  - PURPOSE: To report a case of fungal keratitis caused by Metarrhizium anisopliae,
      which to our knowledge is the first reported case in the United States. METHOD:
      Case report. RESULTS: A 36-year-old female librarian who wore extended-wear soft
      contact lenses was seen by an ophthalmologist on September 11 for an irritated
      right eye, and a corneal ulcer was diagnosed. Symptoms increased by September 27,
      and the patient was referred to another ophthalmologist who cultured the ulcer
      and had scrapings examined, which were Gram-negative for microorganisms. The
      patient was referred to one of the authors (W.J.R.). Her exam on October 1 showed
      vision corrected to 20/25 OD, a 5-mm epithelial defect with a 2.5-mm anterior
      stromal grayish-type infiltrate, and a quiet anterior chamber; the eye did not
      appear to be inflamed. The patient was reexamined on October 4 and was noted to
      have worsening vision. Because the initial cultures remained negative, the
      patient underwent a corneal biopsy, Gram stain, and cultures on October 6.
      Scrapings at the time of the biopsy revealed septate hyphal elements, as did the
      biopsy specimen, and on October 7, the patient was started on a treatment of
      bacitracin ointment once a day and natamycin 5% every hour. The eye gradually
      quieted down. A mold growing from the biopsy culture, which had been sent to a
      reference laboratory in San Antonio, Texas, was identified as M. anisopliae var.
      anisopliae. The patient was subsequently fitted with a rigid gas permeable lens,
      which resulted in a best-corrected visual acuity of 20/20, although glare
      remained a major problem. CONCLUSION: Although not previously reported in the
      United States, M. anisopliae can cause a keratomycosis, and one must consider
      this common insect pathogen in the differential diagnosis of fungal keratitis.

PMID- 11588435
TI  - Ocular involvement in a case of systemic indeterminate cell histiocytosis: a case
      report.
AB  - PURPOSE: To describe ocular involvement in a case of systemic indeterminate cell
      histiocytosis, a rare disease characterized by the proliferation of indistinct
      histiocytes. These histiocytes resemble Langerhans cells but lack Birbeck
      granules. The disease usually occurs in adults, with no predisposition for either
      sex. The clinical features include multiple asymptomatic nodules and cutaneous
      papules. There are no previous reported cases in the literature regarding ocular
      indeterminate cell histiocytosis and its treatment. METHODS: A patient with skin
      papules and hyperpigmentation associated with systemic involvement and corneal
      infiltration was diagnosed with systemic indeterminate cell histiocytosis after a
      skin biopsy. Immunohistochemical examination showed specific surface proteins of
      indeterminate cells, and electron microscopy showed Langerhans-like cells without
      typical Birbeck granules. Progressive and severe photophobia and corneal
      thickening made bilateral corneal transplant necessary. RESULTS: Visual acuity
      remained stable because of the use of systemic immunosuppressors, which decrease
      the recurrence of infiltration after a corneal transplant. CONCLUSION:
      Indeterminate cell histiocytosis is a rare disease and there is no previous
      description of ocular involvement. Infiltrating lesions must be treated with
      corneal transplant and systemic cyclosporin if they decrease visual acuity.

PMID- 11588436
TI  - Opportunistic Roseomonas keratitis.

PMID- 11588437
TI  - Infection after use of nonpreserved human amniotic membrane for the
      reconstruction of the ocular surface.

PMID- 11588438
TI  - Primary graft failure caused by herpes simplex virus type 1.

PMID- 11588439
TI  - Outcome prediction model for very elderly critically ill patients.
AB  - CONTEXT: Very elderly critically ill patients have three possible hospital
      outcomes: discharge to home, discharge to a skilled nursing or rehabilitation
      facility, or death. The factors associated with these outcomes are unknown.
      OBJECTIVE: To develop a three-outcome prediction model for very elderly
      critically ill patients. DESIGN: Retrospective chart abstraction with ordered
      logistic regression analysis. SETTING: Academic medical center. PATIENTS: Four
      hundred and fifty-five patients 85 yrs or older admitted to intensive care units
      (ICU) during 1996 and 1997. MEASUREMENTS AND MAIN RESULTS: A fitted ordinal
      logistic regression predictive model was developed using data from 243 patients
      hospitalized in 1996, and validated on data from 212 patients hospitalized in
      1997. Model variables include age, gender, baseline support level, type of ICU,
      heart rate at ICU admission, use of mechanical ventilation, vasopressors or a
      pulmonary artery catheter during the ICU stay, and the development of
      respiratory, neurologic or hematologic failure or sepsis while in the ICU. When
      tested on the 1997 data, the model was well calibrated and had a high
      discriminant index. CONCLUSIONS: This mathematical model can be used to predict
      the risks of these three hospital outcomes for this population of patients. These
      predictions can provide a context when discussing goals and expectations with
      patients, families, and other healthcare providers and to aid in hospital
      discharge planning.

PMID- 11588440
TI  - Infusion of methylene blue in human septic shock: a pilot, randomized, controlled
      study.
AB  - OBJECTIVE: To evaluate the effects of continuous infusion of methylene blue (MB),
      an inhibitor of the nitric oxide pathway, on hemodynamics and organ functions in
      human septic shock. DESIGN: Prospective, randomized, controlled, open-label,
      pilot study. SETTING: Multidisciplinary intensive care unit of a university
      hospital. PATIENTS: Twenty patients with septic shock diagnosed <24 hrs before
      randomization. INTERVENTIONS: Patients were randomized 1:1 to receive either MB
      (MB group, n = 10) or isotonic saline (control group, n = 10), adjunctive to
      conventional treatment. MB was administered as an intravenous bolus injection (2
      mg/kg), followed 2 hrs later by infusion at stepwise increasing rates of 0.25,
      0.5, 1, and 2 mg/kg/hr that were maintained for 1 hr each. During infusion, mean
      arterial pressure was maintained between 70 and 90 mm Hg, while attempting to
      reduce concurrent adrenergic support. MEASUREMENTS AND MAIN RESULTS: Hemodynamics
      and organ function variables were assessed over a 24-hr period, and the survival
      rate at day 28 was noted. Infusion of MB prevented the stroke volume and the left
      ventricular stroke work indexes from falling and increased mean arterial
      pressure. Compared with the control group, MB reduced the requirement for
      norepinephrine, epinephrine, and dopamine by as much as 87%, 81%, and 40%,
      respectively. Oxygen delivery remained unchanged in the MB group and decreased in
      the control group. MB also reduced the body temperature and the plasma
      concentration of nitrates/nitrites. Leukocytes and organ function variables such
      as bilirubin, alanine aminotransferase, urea, and creatinine were not
      significantly affected. Platelet count decreased in both groups. Five patients
      treated with MB survived vs. three patients receiving conventional treatment.
      CONCLUSIONS: In human septic shock, continuously infused MB counteracts
      myocardial depression, maintains oxygen transport, and reduces concurrent
      adrenergic support. Infusion of MB appears to have no significant adverse effects
      on the selected organ function variables.

PMID- 11588442
TI  - Mean cardiac output by thermodilution with a single controlled injection.
AB  - OBJECTIVE: A new method to estimate mean cardiac output by thermodilution with a
      single duration-controlled injection was evaluated in patients. DESIGN:
      Prospective criterion standard study. SETTING: University hospital cardiac
      surgical intensive care unit and cardiac operation room. PATIENTS: Of 33
      patients, 24 underwent coronary bypass graft surgery, four had a valve
      replacement, and five were treated in the intensive care unit. INTERVENTIONS:
      Interventions consisted of thermodilution cardiac output measurements. One single
      duration-controlled injection of cold fluid was used to calculate cardiac output.
      This controlled injection was performed with a duration equal to one whole
      ventilation cycle of the ventilator. An algorithm adapted to this duration
      controlled injection calculated cardiac output. Moreover, this algorithm has
      properties to reduce errors caused by artificial ventilation and thermal noise.
      MEASUREMENTS AND MAIN RESULTS: In 33 patients, the averaged values of four
      measurements equally spread over the ventilatory cycle (phase-controlled) were
      compared with the values of two single duration-controlled measurements. The
      measurements were performed during periods of stable respiration and circulation.
      No significant difference was observed between the mean of four phase-controlled
      measurements and the mean of the two duration-controlled measurements. The
      cardiac output values in the intensive care patients were significantly higher
      compared with the two other patient groups (p <.05). The difference between the
      two methods could not be subdivided for the three patient groups (p >.05). The
      coefficient of variation of the single duration-controlled thermodilution
      measurements was significantly lower than the single phase-controlled
      measurements, 3% vs. 6% (p <.01). CONCLUSIONS: One single duration-controlled
      injection thermodilution measurement is as accurate and repeatable as the mean of
      four phase-controlled measurements and is clinically feasible.

PMID- 11588443
TI  - Diltiazem to treat sinus tachycardia in critically ill patients: a four-year
      experience.
AB  - OBJECTIVES: To determine whether an intravenous infusion of the calcium channel
      blocker diltiazem was effective and safe in treating sinus tachycardia in
      critically ill adult patients with contraindications to beta-blockers or in whom
      beta-blockers were ineffective. DESIGN: Retrospective chart review. SETTING:
      University medical center. PATIENTS: The records of 171 surgical intensive care
      unit patients with sinus tachycardia treated with intravenous diltiazem were
      evaluated. INTERVENTIONS: In all patients with sinus tachycardia (heart rate >100
      beats/min), heart rate control with intravenous diltiazem was attempted after
      adequate intravascular volume expansion, pain, and anxiety control. In all
      patients, beta-blockade either was contraindicated or (in 7%) had failed.
      Intravenous diltiazem was administered as a slow 10-mg bolus dose (0.1-0.2 mg/kg
      ideal body weight), and then an infusion was started at 5 or 10 mg/hr and
      increased up to 30 mg/hr, as needed, to decrease heart rate to <100 beats/min.
      Variables retrospectively collected included demographic data, preinfusion blood
      pressure, mean arterial pressure, heart rate, and preinfusion pressure-rate
      quotients (pressure-rate quotient = mean arterial pressure / heart rate).
      Intravenous bolus dose, when given, and diltiazem infusion rate and time
      necessary to achieve the target heart rate also were recorded. The lowest heart
      rate recorded within 24 hrs from the initiation of the infusion and the time
      necessary to achieve the lowest heart rate after beginning the infusion were
      recorded. MEASUREMENTS AND RESULTS: Of 171 patients studied, 97 (56%) were
      classified as responders. Multiple linear regression suggested that response
      could be predicted by age, pressure-rate quotients, baseline mean arterial
      pressure, and central nervous system failure. In the responders, a heart rate
      <100 beats/min was achieved in an average of 2 hrs, at a mean diltiazem infusion
      of 13.3 mg/hr. The lowest rate reached by the responders in a 24-hr period
      averaged 86 beats/min and was achieved in 4.8 hrs with a mean infusion rate of
      14.8 mg/hr. Both target and lowest rate values were statistically different from
      baseline heart rate. CONCLUSION: Diltiazem was effective in achieving short-term
      control of heart rate in 56% of the patients, virtually without adverse effects,
      where beta-blockade was contraindicated or ineffective.

PMID- 11588444
TI  - Cardiac troponin I: its contribution to the diagnosis of perioperative myocardial
      infarction and various complications of cardiac surgery.
AB  - OBJECTIVE: To study the value of assaying cardiac troponin I (cTnI) for the early
      diagnosis of perioperative myocardial infarction (PMI) and various complications
      of cardiac surgery. DESIGN: A prospective observational clinical study. SETTING:
      Biochemical laboratory, anesthesia, and cardiac surgery department of Hopital
      Broussais. PATIENTS: Two hundred and sixty consecutive patients undergoing
      cardiac surgery. INTERVENTIONS: All patients underwent coronary artery bypass
      grafting and/or valvular surgery under extracorporeal circulation. Per-operative
      and postoperative follow-up consisted of electrocardiogram, echocardiography
      (mainly by the transesophageal approach), and serial determinations of
      biochemical markers such as creatinine kinase-MB isoenzyme (CK-MB) and cTnI. PMI,
      new ST segment changes, and ventricular arrhythmias were considered postoperative
      adverse cardiac outcome. MEASUREMENTS AND MAIN RESULTS: CTnI was measured before
      cardiopulmonary bypass (T0) and 12 and 24 hrs after (T12, T24). CK-MB was
      measured on arrival in the intensive care unit and on the first postoperative day
      (D1). Patients were divided into three groups according to the type of surgery:
      coronary artery bypass graft (CABG), valvular surgery (VS), or both procedures.
      The plasma CK-MB and cTnI concentrations were high in all patients after
      extracorporeal circulation because of aortic clamping or cardioplegia. The CK-MB
      and cTnI values were higher in the VS group than in the CABG group. Values peaked
      at T12 and fell by T24, except when PMI occurred. Eight patients developed a PMI.
      Patients with PMI had significantly higher cTnI levels at T12 and T24, and higher
      CK-MB values at D1 than patients without PMI. Cutoff values of cTnI for
      diagnosing PMI were >19 microg/L at T12 with 100% sensitivity and 73%
      specificity, and >36 microg/L at T24, with 100% sensitivity and 93% specificity.
      Lower cTnI values were highly suggestive of the absence of PMI after CABG and/or
      VS. Other complications such as ST segment changes, ventricular arrhythmias and
      cardiac failure were indicated by high cTnI levels at T12 and T24. Myocardial
      protective measures were associated with a nonsignificant increase in cTnI
      values. CONCLUSIONS: CTnI is more sensitive and specific than CK-MB for
      diagnosing PMI and other forms of heart failure after cardiac surgery.

PMID- 11588446
TI  - French intensivists do not apply American recommendations regarding decisions to
      forgo life-sustaining therapy.
AB  - OBJECTIVE: Recommendations for making and implementing decisions to forgo life
      sustaining therapy in intensive care units have been developed in the United
      States, but the extent that they are realized in practice has yet to be measured.
      DESIGN: Prospective, multicenter, 4-wk study. For each patient with an
      implemented decision to forgo life-sustaining therapy, the deliberation and
      decision implementation procedures were recorded. SETTING: French intensive care
      units. PATIENTS: All consecutive patients admitted to 26 French intensive care
      units. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1,009 patients
      admitted, 208 died in the intensive care unit. A decision to forgo life
      sustaining therapy was implemented in 105 patients. The number of supportive
      treatments forgone was 2.3 +/- 1.7 per patient. Decisions to forgo sustaining
      therapy were preceded by 3.5 +/- 2.5 deliberation sessions. Proxies were informed
      of the deliberations in 62 (59.1%) cases but participated in only 18 (17.1%)
      decisions. The patient's perception of his or her quality of life was rarely
      evaluated (11.5%), and only rarely did the decision involve evaluating the
      patient's wishes (7.6%), the patient's religious values (7.6%), or the cost of
      treatment (7.6%). Factors most frequently evaluated were medical team advice
      (95.3%), predicted reversibility of acute disease (90.5%), underlying disease
      severity (83.9%), and the patient's quality of life as evaluated by caregivers
      (80.1%). CONCLUSIONS: A decision to withhold or withdraw life-sustaining therapy
      was implemented for half the patients who died in the French intensive care units
      studied. In many cases, the decision was taken without regard for one or more
      factors identified as relevant in U.S. guidelines.

PMID- 11588448
TI  - Clinical factors associated with unexpected critical care management and
      prolonged hospitalization after elective cervical spine surgery.
AB  - OBJECTIVES: To determine preoperative and operative factors associated with the
      need for unanticipated critical care management and prolonged hospitalization
      after cervical spine surgery. DESIGN: Retrospective, case controlled study with
      data collection over 5 yrs. SETTING: Intensive care unit at a Veterans Affairs
      hospital. PATIENTS: A total of 109 patients who underwent elective cervical
      decompression for degenerative disease. INTERVENTIONS: Anterior or posterior
      cervical spine surgery. MEASUREMENTS AND MAIN RESULTS: Data were recorded with
      regard to pre- and postoperative neurologic function, extent of surgery, length
      and cost of hospitalization and critical care, and preoperative co-morbidities.
      Of 109 patients, 16 (15%) required critical care management in the early
      postoperative phase (group I). The remainder (n = 93) represented group II. Group
      I had an average hospital stay of 18.5 days as compared with 6.1 days for group
      II (p <.001) and a cost difference of approximately $26,000. The incidence of
      preexisting myelopathy (69%) and the extent of decompression (2.38 levels) were
      greater in group I than group II (27%, p <.005; 1.67 levels, p <.01). The
      presence of pulmonary disease (p <.03), hypertension (p <.02), cardiovascular
      disease (p <.05), and diabetes mellitus (p <.002) all were associated with the
      need for critical care management and longer hospitalization. CONCLUSIONS: In
      those patients undergoing decompressive cervical surgery for degenerative
      disease, the following factors were linked to the need for unanticipated,
      postoperative critical care and longer hospitalization: multilevel decompression,
      preexisting myelopathy, pulmonary disease, cardiovascular disease, hypertension,
      and diabetes mellitus.

PMID- 11588447
TI  - Symptoms of anxiety and depression in family members of intensive care unit
      patients: ethical hypothesis regarding decision-making capacity.
AB  - OBJECTIVE: Anxiety and depression may have a major impact on a person's ability
      to make decisions. Characterization of symptoms that reflect anxiety and
      depression in family members visiting intensive care patients should be of major
      relevance to the ethics of involving family members in decision-making,
      particularly about end-of-life issues. DESIGN: Prospective multicenter study.
      SETTING: Forty-three French intensive care units (37 adult and six pediatric);
      each unit included 15 patients admitted for longer than 2 days. PATIENTS: Six
      hundred thirty-seven patients and 920 family members. INTERVENTIONS: Intensive
      care unit characteristics and data on the patient and family members were
      collected. Family members completed the Hospital Anxiety and Depression Scale to
      allow evaluation of the prevalence and potential factors associated with symptoms
      of anxiety and depression. MEASUREMENTS AND MAIN RESULTS: Of 920 Hospital Anxiety
      and Depression Scale questionnaires that were completed by family members, all
      items were completed in 836 questionnaires, which formed the basis for this
      study. The prevalence of symptoms of anxiety and depression in family members was
      69.1% and 35.4%, respectively. Symptoms of anxiety or depression were present in
      72.7% of family members and 84% of spouses. Factors associated with symptoms of
      anxiety in a multivariate model included patient-related factors (absence of
      chronic disease), family-related factors (spouse, female gender, desire for
      professional psychological help, help being received by general practitioner),
      and caregiver-related factors (absence of regular physician and nurse meetings,
      absence of a room used only for meetings with family members). The multivariate
      model also identified three groups of factors associated with symptoms of
      depression: patient-related (age), family-related (spouse, female gender, not of
      French descent), and caregiver-related (no waiting room, perceived contradictions
      in the information provided by caregivers). CONCLUSIONS: More than two-thirds of
      family members visiting patients in the intensive care unit suffer from symptoms
      of anxiety or depression. Involvement of anxious or depressed family members in
      end-of-life decisions should be carefully discussed.

PMID- 11588449
TI  - Effects of normothermia versus hypothermia on extravascular lung water and serum
      cytokines during cardiopulmonary bypass: a randomized, controlled trial.
AB  - OBJECTIVE: To evaluate the influence of perfusion temperature on the systemic
      effects of cardiopulmonary bypass (CPB), including extravascular lung water index
      (EVLWI), and serum cytokines. DESIGN: Prospective, randomized, controlled study.
      SETTING: Cardiothoracic intensive care unit of a university hospital. PATIENTS:
      Patients undergoing elective coronary artery bypass grafting. INTERVENTIONS:
      Twenty-one patients undergoing elective coronary artery bypass grafting were
      randomly assigned to receive either normothermic bypass (36 degrees C, n = 8)
      with intermittent antegrade warm blood cardioplegia (IAWBC), or hypothermic (32
      degrees C, n = 13) CPB with cold crystalloid cardioplegia. MEASUREMENTS AND MAIN
      RESULTS: Mean arterial pressure, heart rate, cardiac output, systemic vascular
      resistance, mean pulmonary arterial pressure, and pulmonary vascular resistance
      were determined at baseline, i.e., after induction of anesthesia but before
      sternal opening (T-1), at arrival in the intensive care unit (T0), and 4 hrs
      (T4), 8 hrs (T8), and 24 hrs (T24) after surgery. EVLWI, intrathoracic blood
      volume index (ITBVI), and EVLW/ITBV ratio were obtained by using thermal dye
      dilution utilizing an arterial thermistor-tipped fiberoptic catheter and were
      recorded at T-1, T0, T4, T8, and T24. Serial blood samples for cytokine
      measurements were obtained at each hemodynamic measurement time point. Before,
      during, and after CPB, there were no differences in the conventional hemodynamic
      measurements between the groups. There were no changes in EVLWI up to T8 in
      either group. Furthermore, no change in the ratio EVLW/ITBW was observed between
      the groups at any time, further indicating the absence of a change in pulmonary
      permeability. Plasma levels of interleukin-6, tumor necrosis factor-alpha, and
      interleukin-10 increased during and after CPB, independently of the perfusion
      temperature. CONCLUSION: Normothermic CPB is not associated with additional
      inflammatory and related systemic adverse effects regarding cytokine production
      and EVLWI as compared with mild hypothermia. The potential temperature-dependent
      release of cytokines and subsequent inflammation has not been observed and
      normothermic CPB may be seen as a safe technique regarding this issue.

PMID- 11588450
TI  - Epidemiology, management, and outcome of severe acute renal failure of critical
      illness in Australia.
AB  - OBJECTIVE: To study the epidemiology, style of management, and outcome of
      intensive care patients with acute renal failure requiring replacement therapy in
      Australia. DESIGN: Prospective epidemiologic study. SETTING: Australian adult
      intensive care units providing acute renal replacement therapy. PATIENTS: Adult
      intensive care patients with acute renal failure treated with renal replacement
      therapy. INTERVENTIONS: Demographic and clinical data collection for 3 months.
      MEASUREMENTS AND MAIN RESULTS: A standardized data collection form for each case
      of severe acute renal failure was used to collect demographic, biochemical,
      clinical, and outcome data. Severe acute renal failure affected 299 patients
      (approximately eight cases per 100,000 adults per year). Among these patients, 99
      (33.1%) had impaired baseline renal function, 238 (79.6%) needed mechanical
      ventilation, and 232 (77.6%) needed continuous vasoactive drug administration.
      Critical care physicians controlled patient care and renal replacement therapy in
      289 cases (96.7%). Critical care nurses performed such therapy alone in 288
      (96.3%) cases. Continuous renal replacement therapy was used in 292 (97.7%)
      patients. There was no nephrological input in 173 (57.8%) cases. Predicted
      mortality rates were 52.1% by Simplified Acute Physiology Score II, 49.5% by
      Acute Physiology and Chronic Health Evaluation II score, and 51.9% by an acute
      renal failure-specific score. Actual mortality rate was 46.8%. Only 25 (15.7%)
      patients were dialysis-dependent at hospital discharge. Of these patients, 20
      (80%) had premorbid chronic impairment of renal function. CONCLUSION: In
      Australia, critical care physicians and nurses manage severe acute renal failure
      with limited consultative nephrological input. Renal replacement therapy is
      continuous and outcomes are satisfactory. Our findings support the view that this
      approach to management of severe acute renal failure is safe.

PMID- 11588451
TI  - Gastric feeding with erythromycin is equivalent to transpyloric feeding in the
      critically ill.
AB  - OBJECTIVE: To determine whether adding erythromycin to a gastric feeding regimen
      could render it as effective in meeting nutritional needs as transpyloric
      feeding. DESIGN: Randomized, controlled study. SETTING: University hospital
      medical, surgical, and neurologic care intensive care units. PATIENTS: Critically
      ill patients, requiring a projected 96 hrs of enteral feeding, who had no
      specific indication for tube location (gastric or transpyloric). Eighty patients
      were randomized. INTERVENTIONS: Patients were randomized to gastric feeding with
      erythromycin (200 mg iv) given every 8 hrs or feeding through a transpylorically
      placed feeding tube. Goal rate and feeding advancement were determined by
      protocol. MEASUREMENTS AND MAIN RESULTS: During the 96-hr period, the gastric
      group received 74% of their goal calories and the transpyloric group received
      67%. The only day on which gastric feedings were superior was the first study
      day, where the gastric group attained 55% of their goal, compared with 44% in the
      transpyloric group. This 1-day difference was the result of an initial failure of
      tube placement in some subjects. Exclusion of these patients did not change
      overall results. Nutritional indexes, length of stay in the intensive care unit,
      ventilator dependence, and survival were not different between the two groups.
      CONCLUSIONS: Gastric feeding with erythromycin as a prokinetic is equivalent to
      transpyloric feeding in meeting the nutritional goals of the critically ill.

PMID- 11588453
TI  - Reliable tidal volume estimates at the airway opening with an infant monitor
      during high-frequency oscillatory ventilation.
AB  - OBJECTIVE: To assess the suitability of a hot-wire anemometer infant monitoring
      system (Florian, Acutronic Medical Systems AG, Hirzel, Switzerland) for measuring
      flow and tidal volume (Vt) proximal to the endotracheal tube during high
      frequency oscillatory ventilation. DESIGN: In vitro model study. SETTING:
      Respiratory research laboratory. SUBJECT: In vitro lung model simulating moderate
      to severe respiratory distress. INTERVENTION: The lung model was ventilated with
      a SensorMedics 3100A ventilator. Vt was recorded from the monitor display (Vt
      disp) and compared with the gold standard (Vt-adiab), which was calculated using
      the adiabatic gas equation from pressure changes inside the model. MEASUREMENTS
      AND MAIN RESULTS: A range of Vt (1-10 mL), frequencies (5-15 Hz), pressure
      amplitudes (10-90 cm H2O), inspiratory times (30% to 50%), and Fio2 (0.21-1.0)
      was used. Accuracy was determined by using modified Bland-Altman plots (95%
      limits of agreement). An exponential decrease in Vt was observed with increasing
      oscillatory frequency. Mean DeltaVt-disp was 0.6 mL (limits of agreement, -1.0 to
      2.1) with a linear frequency dependence. Mean DeltaVt-disp was -0.2 mL (limits of
      agreement, -0.5 to 0.1) with increasing pressure amplitude and -0.2 mL (limits of
      agreement, -0.3 to -0.1) with increasing inspiratory time. Humidity and heating
      did not affect error, whereas increasing Fio2 from 0.21 to 1.0 increased mean
      error by 6.3% (+/-2.5%). CONCLUSIONS: The Florian infant hot-wire flowmeter and
      monitoring system provides reliable measurements of Vt at the airway opening
      during high-frequency oscillatory ventilation when employed at frequencies of 8
      13 Hz. The bedside application could improve monitoring of patients receiving
      high-frequency oscillatory ventilation, favor a better understanding of the
      physiologic consequences of different high-frequency oscillatory ventilation
      strategies, and therefore optimize treatment.

PMID- 11588452
TI  - Natural inhibitors of neutrophil function in acute respiratory distress syndrome.
AB  - OBJECTIVE: Neutrophils play a key role in the physiopathogenesis of acute lung
      injury in general and acute respiratory distress syndrome (ARDS) in particular.
      To identify the anti-inflammatory mediators with a protective effect on lung
      tissue damage in ARDS, we correlated the concentration of the Clara cell 16-kD
      protein (CC16; an inhibitor of neutrophil chemotaxis), angiogenin (an inhibitor
      of degranulation), and the total radical oxygen neutralizing activity with the
      amount of elastase (a marker of neutrophil activation) and with the Pao2/Fio2
      ratio, which is inversely related to lung injury. SETTING: University hospital.
      PATIENTS: Patients with ARDS (n = 12) and patients at risk for developing ARDS (n
      = 14). INTERVENTIONS: Patients underwent bronchoalveolar lavage 12 hrs after
      diagnosis of ARDS or at-risk status. MEASUREMENTS AND MAIN RESULTS: The amount of
      CC16 and radical oxygen neutralizing activity was not significantly different in
      patients with or at risk for ARDS. In contrast, the amount (mean +/- sem) of
      angiogenin in the bronchoalveolar lavage of ARDS patients (45 +/- 14 ng/mL, n =
      12) was increased 11-fold (p <.05) compared with patients at risk for ARDS (4 +/-
      1 ng/mL, n = 14). In patients with ARDS, the amount of protein and angiogenin in
      bronchoalveolar lavage increased with decreasing concentration of CC16 (p <.05).
      In addition, CC16 correlated with the Pao2/Fio2 ratio (p <.05) and inversely with
      the amount of elastase (p <.05) and thus may be regarded as a reliable protective
      agent for lung injury. CONCLUSION: A high concentration of CC16, a natural
      inhibitor of neutrophil function, decreases neutrophil-mediated lung damage of
      patients with ARDS. Strategies to increase natural anti-inflammatory agents, and
      thus influence the disruption of the balance between natural inflammatory and
      anti-inflammatory or protective factors, could be useful to modulate the tissue
      destruction and the course of ARDS.

PMID- 11588454
TI  - Intravenous omeprazole in critically ill patients: a randomized, crossover study
      comparing 40 with 80 mg plus 8 mg/hour on intragastric pH.
AB  - OBJECTIVE: To compare intravenous omeprazole 40-mg single dose with 8 mg/hr after
      an 80-mg bolus injection on 24-hr intragastric pH in intensive care unit (ICU)
      ventilated patients. DESIGN: Prospective, randomized crossover study. SETTING: A
      42-bed medicosurgical ICU in a university hospital PATIENTS: Medicosurgical
      ventilated patients at risk of gastrointestinal bleeding. INTERVENTIONS: After
      baseline determination of intragastric pH, patients were randomly allocated to
      have a 40-mg iv omeprazole bolus injection (arm I) or 80 mg bolus, followed by 8
      mg/hr continuous infusion for 24 hrs (arm II). After a 24-hr washout period, the
      opposite regimen was given in a crossover design. Intragastric pH was determined
      at regular intervals during the treatment period. RESULTS: In ten patients
      completing the protocol, the intragastric pH was similar for the two regimens for
      the first 12 hrs. The area under the pH curve was 5.51 +/- 0.48 for arm I
      compared with 6.02 +/- 0.33 for arm II (NS). Time to reach a pH of 4 or 6 was not
      significantly different for the two regimens. Time spent with a pH greater than 4
      and 6 for the first 12 hrs was 10.11 +/- 1.14 and 8.31 +/- 1.16 hrs vs. 10.11 +/-
      0.75 and 7.43 +/- 1.19 hrs for arm I and arm II, respectively (NS). When the
      first 24 hrs are considered, the area under the pH curve was 5.17 +/- 0.49 for
      arm I vs. 6.36 +/- 0.25 for arm II (p <.05). Time spent with a pH greater than 4
      and 6 was 17.2 +/- 2.4 hrs and 12.63 +/- 2.22 vs. 23 +/- 0.41 and 19.48 +/- 1.63
      in arm I and arm II, respectively (p <.05 and.01). An intragastric pH above 6 for
      all determinations was only observed in arm II. CONCLUSIONS: In critically ill
      patients, intravenous omeprazole 40 mg single dose is as effective as 8 mg/hr
      after an 80-mg bolus injection on mean intragastric pH, time spent with a pH
      greater than 4 and 6, but only for the first 12 hrs. If an intragastric pH
      greater than 6 has to be maintained for 24 hrs in all patients, an 80-mg bolus
      followed by 8 mg/hr iv omeprazole is to be given. Our data suggest that in
      several critically ill patients, a single 40-mg iv omeprazole bolus injection may
      be able to achieve stress ulcer prophylaxis and that 40 mg twice daily should be
      compared with 8 mg/hr after an 80-mg bolus injection in bleeding ulcers.

PMID- 11588456
TI  - Testosterone administration in severe burns ameliorates muscle catabolism.
AB  - OBJECTIVE: To assess the effects of testosterone administration on muscle protein
      metabolism after severe burn injury. We hypothesized that restoration of blood
      testosterone concentrations would restore an important anabolic stimulus to
      skeletal muscle, and would further increase the anabolic response of muscle to
      amino acid supplementation. DESIGN: Pre- and postintervention trial conducted
      between September 1997 and July 1999. SETTING: Burn intensive care unit.
      PATIENTS: Six severely burned male patients (>70% total body surface area).
      INTERVENTION: Testosterone enanthate, 200 mg/wk (intramuscularly), for 2 wks.
      MEASUREMENTS AND MAIN RESULTS: Muscle protein synthesis, breakdown, and amino
      acid kinetics were determined. After a basal period in each study, we
      subsequently investigated the response to acute amino acid supplementation during
      enteral feeding. Total testosterone increased significantly from baseline to the
      low normal range after 1 wk, and to upper normal range after two injections (p
      <.001). Protein synthesis was unchanged, however, protein synthetic efficiency
      increased 2-fold (p <.01). Protein breakdown decreased almost 2-fold after
      testosterone enanthate (p <.05), resulting in an improvement in net amino acid
      balance to a value that was approximately zero (p <.0001). Amino acid
      supplementation at either time point provided no additional effects. CONCLUSIONS:
      Restoration of blood testosterone can ameliorate the muscle catabolism of severe
      burn injury with normal feedings.

PMID- 11588457
TI  - Intraoperative prostaglandin E1 improves antimicrobial and inflammatory responses
      in alveolar immune cells.
AB  - OBJECTIVE: Anesthesia and surgery decrease antimicrobial and increase
      proinflammatory functions of alveolar immune cells. Thus, anti-inflammatory
      agents that do not further suppress antimicrobial functions are required. We
      tested the hypothesis that intraoperative prostaglandin E1 (PGE1) suppresses
      proinflammatory responses and prevents the reduction in antimicrobial responses
      of alveolar immune cells. DESIGN: Prospective, randomized, controlled, double
      blind study. SETTING: University hospital. PATIENTS: A total of 40 patients
      undergoing elective orthopedic surgery under propofol/fentanyl anesthesia.
      INTERVENTION: In double-blind fashion, the patients received PGE1 from the
      beginning to the end of surgery (PGE1 group, n = 20) or nothing (control group, n
      = 20). METHODS AND MAIN RESULTS: Alveolar immune cells were harvested by
      bronchoalveolar lavage immediately after induction of anesthesia; 2, 4, and 6 hrs
      after induction of anesthesia; and at the end of surgery. We measured opsonized
      and nonopsonized phagocytosis. Microbicidal activity was evaluated to directly
      kill Listeria monocytogenes in alveolar macrophages. Finally, we determined the
      expression of proinflammatory cytokines including interleukin (IL)-1beta, IL-8,
      interferon-gamma, and tumor necrosis factor-alpha, and that of anti-inflammatory
      cytokines (IL-4 and IL-10) by semiquantitative polymerase chain reaction.
      Nonopsonized and opsonized phagocytosis and microbicidal activity of alveolar
      macrophages decreased and the expression of genes for all pro- and anti
      inflammatory cytokines increased significantly over time in both groups. Starting
      2-4 hrs after induction of anesthesia, the increases in gene expression of
      proinflammatory cytokines were 1.5-3 times smaller in the PGE1 than in the
      control group. Starting 6 hrs after anesthesia, the increase in gene expression
      of IL-10 was 1.5-3 times greater in the PGE1 than in the control group.
      Intraoperative decreases in phagocytic and microbial activities were the same in
      the two groups. CONCLUSION: Intraoperative PGE1 not only suppressed
      proinflammatory responses, but also protected antimicrobial functions of alveolar
      macrophages, possibly because PGE1 is mostly inactivated in the pulmonary
      intravascular space. Our results suggest that intraoperative PGE1 protects the
      pulmonary immune defense in alveolar immune cells.

PMID- 11588459
TI  - Autoantibodies to lipids in bronchoalveolar lavage fluid of patients with acute
      respiratory distress syndrome.
AB  - OBJECTIVE: To investigate the presence of autoantibodies to lipids in the
      bronchoalveolar lavage (BAL) fluid from adult patients with acute respiratory
      distress syndrome (ARDS). DESIGN: Analysis of immunoglobulin G (IgG) in BAL fluid
      by electrophoresis followed by immunoblotting and characterization of
      immunoglobulins as antilipid autoantibodies. SETTING: Intensive care unit of a
      university hospital and two research university laboratories. SUBJECTS: Twenty
      seven mechanically ventilated patients in total, including nine patients with
      ARDS and two control groups. INTERVENTIONS: Patients were ventilated with a
      mechanical ventilation mode. Six aliquots of 20-mL sterile normal saline at 37
      degrees C were infused through the working channel of the bronchoscope.
      MEASUREMENTS: Total protein, detection of IgG by electrophoresis followed by
      immunoblotting, and characterization of IgG by enzyme-linked immunosorbent assay
      using different lipids as target antigens. MAIN RESULTS: Antiphospholipid
      autoantibodies are present in BAL fluid of ARDS patients. Among the phospholipids
      tested, phosphatidic acid and phosphatidylserine gave the most significant
      activity. The IgG fraction, purified from BAL fluids by affinity chromatography,
      gave the same pattern of binding as that of the BAL fluid. CONCLUSION: The
      presence of antiphospholipid autoantibodies in BAL fluid suggests involvement of
      autoimmune mechanisms in the pathogenesis of ARDS.

PMID- 11588461
TI  - Upper digestive intolerance during enteral nutrition in critically ill patients:
      frequency, risk factors, and complications.
AB  - OBJECTIVE: To study the frequency of and risk factors for increased gastric
      aspirate volume (GAV) and upper digestive intolerance and their complications
      during enteral nutrition (EN) in critically ill patients. DESIGN: Prospective
      observational study. SETTING: Intensive care unit (ICU) in a general hospital.
      PATIENTS: A total of 153 patients with nasogastric tube feeding. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Upper digestive intolerance was considered
      when GAV was between 150 and 500 mL at two consecutive measurements, when it was
      >500 mL, or when vomiting occurred. Forty-nine patients (32%; 95% confidence
      interval [CI], 25%-42%) presented increased GAV after a median EN duration of 2
      days (range, 1-16 days), and 70 patients (46%; 95% CI, 38%-54%) presented upper
      digestive intolerance. Independent risk factors for high GAV were GAV >20 mL
      before the start of EN (odds ratio [OR], 2.16; 95% CI, 1.11-4.18; p =.02), GAV
      >100 mL during EN (OR, 1.49; 95% CI, 1.01-2.19; p <.05), sedation during EN (OR,
      1.78; 95% CI, 1.17-2.71; p =.007), use of catecholamines during EN (OR, 1.81; 95%
      CI, 1.21-2.70; p =.004). Complications related to high GAV were a lower feed
      intake (15 +/- 7 vs. 19 +/- 8 kcal/kg/day; p =.0004) and vomiting (53% vs. 23%; p
      =.0002). Complications related to upper digestive intolerance were the
      development of pneumonia (43% vs. 24%; p =.01), a longer ICU stay (23 +/- 21 vs.
      15 +/- 16 days; p =.007), and a higher ICU mortality (41% vs. 25%; p =.03), even
      after adjustment for Simplified Acute Physiology Score II (OR, 1.48; 95% CI, 1.04
      2.10; p =.028). CONCLUSION: In ICU patients receiving nasogastric tube feeding,
      high gastric aspirate volume was frequent, occurred early, and was more frequent
      in patients with sedation or catecholamines. High gastric aspirate volume was an
      early marker of upper digestive intolerance, which was associated with a higher
      incidence of nosocomial pneumonia, a longer ICU stay, and a higher ICU mortality.

PMID- 11588462
TI  - Differential activation pattern of redox-sensitive transcription factors and
      stress-inducible dilator systems heme oxygenase-1 and inducible nitric oxide
      synthase in hemorrhagic and endotoxic shock.
AB  - OBJECTIVE: To investigate the role of redox-sensitive transcription factors
      nuclear factor kappa-B (NF-kappaB) or activator protein-1 (AP-1) for hepatic gene
      expression of heme oxygenase (HO)-1 and inducible nitric oxide synthase (iNOS) in
      models of hemorrhagic or endotoxic shock. DESIGN: Prospective controlled
      laboratory study. SETTING: Animal research laboratory at a university hospital.
      SUBJECTS: Male Sprague-Dawley rats (250-350 g). INTERVENTIONS: After anesthesia,
      animals were assigned to hemorrhagic shock (mean arterial pressure 35-40 mm Hg
      for 60 mins), sham operation, or endotoxemia (1 mg/kg intraperitoneally). To
      assess the role of reactive oxygen species for activation of NF-kappaB or AP-1,
      animals were treated with the antioxidant trolox (6 mg/kg body weight). In
      additional experiments, animals were pretreated with dexamethasone (10 mg/kg body
      weight), an inhibitor of the transactivating function of DNA-bound AP-1 or with
      actinomycin-D (2 mg/kg body weight), an inhibitor of DNA-directed RNA synthesis.
      Activation of NF-kappaB or AP-1 was assessed by electrophoretic mobility shift
      assay. HO-1 and iNOS gene expression were assessed by Northern and Western blot.
      MEASUREMENTS AND MAIN RESULTS: Hemorrhage and resuscitation induced hepatic HO-1
      transcripts 12-fold. Induction was abolished by actinomycin-D and was attenuated
      by dexamethasone and the antioxidant trolox. Activation of AP-1 was observed
      after hemorrhagic but not after endotoxic shock. AP-1 activation was inhibitable
      by trolox and correlated with accumulation of HO-1 transcripts. In contrast, a
      weak activation of NF-kappaB was observed after hemorrhage that was not affected
      by trolox. A profound activation of NF-kappaB after endotoxic shock correlated
      with induction of iNOS but failed to induce HO-1 transcripts. CONCLUSIONS: These
      data suggest that AP-1 but not NF-kappaB activation is dependent on reactive
      oxygen intermediates in vivo and contributes to HO-1 gene expression. Thus, AP-1
      dependent HO-1 induction under oxidative stress conditions may subserve a similar
      function as a stress-inducible vasodilator system as does NF-kappaB-dependent
      iNOS expression in liver inflammation.

PMID- 11588463
TI  - Effects of arteriovenous extracorporeal therapy on hemodynamic stability,
      ventilation, and oxygenation in normal lambs.
AB  - OBJECTIVE: To evaluate hemodynamic stability and gas exchange in a neonatal
      animal model of pumpless arteriovenous extracorporeal membrane oxygenation (AV
      ECMO) with extracorporeal shunt flow of up to 15% of cardiac output during
      variable ventilation and oxygenation. DESIGN: Prospective study. SETTING:
      Research laboratory in a hospital. SUBJECTS: Seven lambs (5.5 +/- 0.6 kg, mean +/
      sd). INTERVENTIONS: The lambs initially were anesthetized by 50 mg/kg ketamine
      intravenously. After tracheostomy, the lambs were mechanically ventilated and
      paralyzed by using 1 mg/kg vecuronium bromide followed by 0.1 mg.kg(-1).hr(-1).
      One femoral vein was cannulated with a pulmonary artery flotation catheter and
      used for cardiac output and pulmonary artery pressure measurements. A femoral
      artery was cannulated for measuring mean arterial blood pressure, measuring heart
      rate, and blood sampling for gas exchange analyses. Finally, the right internal
      jugular vein and carotid artery were cannulated and used for the AV-ECMO.
      Normothermia (38 +/- 0.5 degrees C), fluid balance (5 mL.kg(-1).hr(-1) normal
      saline), and anesthesia (5 mg.kg(-1).hr(-1), intravenous ketamine) were
      maintained. Ventilator settings were adjusted to establish a baseline Paco2 (25
      35 mm Hg) at an Fio2 of 0.4. The AV-ECMO circuit was established by using a
      hollow fiber oxygenator, primed with maternal sheep blood (150-200 mL).
      MEASUREMENTS AND MAIN RESULTS: The physiologic effects of the AV-ECMO shunt were
      evaluated at 15, 25, and 40 mL.kg(-1).hr(-1) ECMO flow, corresponding roughly to
      4%, 8%, and 15% of the cardiac output values. The baseline minute volume was
      maintained during stepwise increases in arteriovenous shunt. A significant
      increase in endogenous cardiac output occurred at arteriovenous shunt of 25 and
      40 mL.kg(-1).hr(-1) (analysis of variance followed by Tukey-Kramer multiple
      comparisons test), which was attributed to a significant increase of 30% in the
      heart rate. Effective cardiac output (difference between the thermodilution value
      and the AV-ECMO flow rate) and mean arterial blood pressure were not
      significantly changed. CO2 removal, measured at 15% arteriovenous shunt, was
      significantly increased with decreasing ventilation to 25% and 50% of the
      baseline (analysis of variance and Tukey-Kramer test). Oxygenation through the
      membrane was measured after reducing inspired Fio2 from 0.4 to 0.21, 0.15, and
      0.10 with 15% arteriovenous shunt and baseline minute ventilation. Oxygen
      delivery by the oxygenator was significantly increased at Fio2 of 0.10, providing
      a maximum of 19.5% of the total oxygen consumption at an arterial hemoglobin
      oxygen saturation of 60%. CONCLUSIONS: Healthy lambs are capable of maintaining
      effective cardiac output in the presence of moderate arteriovenous shunts (15%).
      AV-ECMO may provide efficient ventilatory support in the neonatal population with
      hypercapnia. The amount of oxygen delivery with AV-ECMO depends on arterial
      desaturation.

PMID- 11588465
TI  - Hemolysis in stored red blood cell concentrates: modulation by haptoglobin or
      ulinastatin, a protease inhibitor.
AB  - OBJECTIVE: Polymorphonuclear leukocyte elastase may injure various tissues. The
      release of polymorphonuclear leukocyte elastase induced by various stimuli was
      reported to be inhibited by a protease inhibitor, ulinastatin. In stored blood
      preparations, polymorphonuclear leukocyte elastase increases depending on the
      storage days as hemolysis increases. We hypothesized that polymorphonuclear
      leukocyte elastase might be one of the factors inducing hemolysis in stored
      blood. Haptoglobin binds to free hemoglobin to reduce hemolysis. The purpose of
      the study was to investigate the effects of ulinastatin on hemolysis in blood
      preparations in comparison with haptoglobin. DESIGN: In vitro study. SETTING:
      Laboratory in a university hospital. SUBJECTS: Nine 2-day-old packs of red blood
      cell concentrates (CRC) in 400 mL each of mannitol, adenine, glucose, phosphate,
      and citrate (MAP) (MAP-CRC) from the Japan Red Cross Society. INTERVENTIONS: Each
      MAP-CRC was divided into three different packs of equal amount and was treated
      with 10 mL of saline (control group), 200 units of haptoglobin, or 50,000 units
      of ulinastatin. They were stored at 4 degrees C. MEASUREMENTS AND MAIN RESULTS:
      Supernatant concentrations of total and free hemoglobin, total haptoglobin,
      polymorphonuclear leukocyte elastase, and potassium were measured for 25 days.
      Free haptoglobin concentration was calculated. Total and free hemoglobin
      concentrations increased significantly depending on the storage days in the
      control group, whereas haptoglobin and ulinastatin groups showed no increase.
      Total and free haptoglobin concentrations were significantly higher in the
      haptoglobin group than in the other two groups. Free haptoglobin concentrations
      were 0 after 5 days of storage in the control and ulinastatin groups.
      Polymorphonuclear leukocyte elastase concentrations increased with the increase
      in storage days without any differences among the three groups. Potassium
      concentration increased according to the storage and showed the highest value in
      the control group. CONCLUSIONS: Adding haptoglobin or ulinastatin to MAP-CRC was
      useful to suppress hemolysis during storage of the preparation. The
      polymorphonuclear leukocyte elastase might not be involved in the mechanisms of
      hemolysis in MAP-CRC stored for 25 days.

PMID- 11588467
TI  - Regional blood flow during periodic acceleration.
AB  - OBJECTIVE: To determine whether a motion platform that imparts noninvasive
      periodic acceleration (pGz) forces to the body causes systemic vasodilation and
      changes local organ blood flow. DESIGN: Prospective paired blocked design.
      SETTING: Medical center research laboratory. SUBJECTS: Juvenile Yorkshire pigs.
      INTERVENTIONS: Juvenile pigs (12 kg) were anesthetized, paralyzed, and placed on
      a motion platform that oscillated at a frequency of 4 Hz and a force of
      approximately 0.4 G. MEASUREMENTS AND MAIN RESULTS: Regional blood flows, as
      assessed by colored microspheres, increased during pGz relative to values
      obtained before pGz. Blood flow (mL.min-1.100 g-1) significantly increased to the
      epicardium (71%), endocardium (93%), cerebrum (183%), brain stem (177%), renal
      cortex (53%), ileal mucosa (69%), gastric antral mucosa (72%), and liver (86%).
      Spleen and skeletal muscle blood flow increased without statistical significance,
      38% and 158% with pGz, relative to paired control values. Regional blood flows
      returned to baseline 10 mins after discontinuation of pGz, except in the
      myocardial layers, where blood flow remained significantly elevated. There was no
      difference compared with baseline in heart rate, arterial blood gases, and blood
      pressure, but serum nitrite concentration was significantly higher (58%) during
      pGz. In another series of animals, pGz increased pulmonary artery blood flow
      directly proportional to the magnitude of the applied acceleration force with
      frequency held constant. CONCLUSIONS: Periodic sinusoidal inertial forces in the
      spinal axis increase blood flow to tissues. The increased blood flow is
      reversible and may be caused by vasodilation secondary to local mediator release.
      These effects may be desirable in clinical conditions of low tissue oxygen
      delivery and perfusion.

PMID- 11588469
TI  - N-acetylcysteine increases cerebral perfusion pressure in pigs with fulminant
      hepatic failure.
AB  - OBJECTIVE: Intravenous administration of N-acetylcysteine beyond 15 hrs reduces
      mortality rates in patients suffering from paracetamol-induced fulminant hepatic
      failure, although the mechanism of the therapeutic benefit remains unclear. We
      hypothesized increased survival to be caused by improved hemodynamic performance.
      The main objective for the study was to explore the effect of N-acetylcysteine on
      hemodynamics, oxygen transport, and regional blood flow in pigs with fulminant
      hepatic failure. DESIGN: Prospective, randomized, controlled trial. SETTING:
      Surgical research laboratory in a university hospital. SUBJECTS: Female Norwegian
      Landrace pigs. INTERVENTIONS: Fulminant hepatic failure was induced by a total
      liver devascularization procedure. Five hours later, the pigs were allocated to N
      acetylcysteine treatment (150 mg.kg-1 in 100 mL of 0.9% saline over 15 mins,
      followed by 50 mg.kg-1 in 500 mL of 0.9% saline over a period of 4 hrs) or
      placebo. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure stabilized in the
      N-acetylcysteine group and increased slightly during the last 2 hrs (pGT =.009).
      Thus, mean arterial pressure was significantly higher compared with placebo after
      3 hrs (p =.01). Cerebral perfusion pressure was significantly higher during the
      last 2 hrs in the N-acetylcysteine group (pGT =.033). Common carotid artery flow
      also increased and was maintained at a higher level compared with placebo (pG
      =.027). Systemic vascular resistance index initially decreased but then gradually
      increased (pGT <.001). Cardiac index increased after 15 mins of N-acetylcysteine
      infusion, causing a significant interaction (pGT =.038), but did not differ after
      3 hrs. No significant differences in hindleg and mesentery hemodynamics were
      found. A short-lived increase in oxygen delivery caused by a temporary increase
      in cardiac index was observed but without any corresponding increase in oxygen
      consumption. CONCLUSIONS: Intravenous N-acetylcysteine infusion increases
      cerebral perfusion pressure in pigs with fulminant hepatic failure. Earlier
      reported effects on oxygen transport and uptake could not be confirmed.

PMID- 11588470
TI  - Use of bispectral electroencephalogram monitoring to assess neurologic status in
      unsedated, critically ill patients.
AB  - OBJECTIVE: To test whether spectral indices derived from the electroencephalogram
      (EEG), and especially the bispectral index (BIS), can be used as measures of
      neurologic status in unsedated, critically ill patients. DESIGN: Prospective,
      observational study. SETTING: Medical intensive care unit (ICU) of a university
      affiliated teaching hospital. PATIENTS: Thirty-one awake, unsedated critically
      ill adults were assessed in 108 separate sessions. MEASUREMENTS AND MAIN RESULTS:
      In each session, severity of illness was assessed by the Acute Physiology and
      Chronic Health Evaluation (APACHE III). The APACHE III Acute Physiology Score was
      used to quantify the degree of physiologic derangement. Neurologic function was
      assessed using the APACHE III Neurologic Score, the Glasgow Coma Scale, the
      Reaction Level Scale, and the Modified Ramsay Sedation Scale. All indices were
      plotted against various spectral parameters of the EEG, including BIS, an
      empirical index of EEG activity that is scaled from 0 to 100. BIS was
      significantly (p <.05) correlated with neurologic score regardless of scoring
      system used and was more strongly correlated than any other EEG spectral
      parameter. Better neurologic function was associated with higher values of BIS.
      In multivariate analysis, the combination of BIS and relative power in the theta
      band of the EEG accounted for 38% of the variability in the Glasgow Coma Scale.
      CONCLUSIONS: BIS provides a reliable index of neurologic status in awake,
      unsedated, critically ill patients. Further research is needed to determine
      whether the effects of neurologic status and pharmacologic sedation upon EEG are
      additive, whether BIS can be used to assess pharmacologic sedation in the
      critically ill patient population, and whether such objective measures of
      neurologic status have prognostic value.

PMID- 11588471
TI  - End-of-life care in the intensive care unit: a research agenda.
AB  - BACKGROUND: The intensive care unit (ICU) represents a unique clinical setting in
      which mortality is relatively high and the professional culture tends to be one
      of "rescue therapy" using technological and invasive interventions. For these
      reasons, the ICU is an important environment for understanding and improving end
      of-life care. Although there have been consensus statements and review articles
      on end-of-life care in the ICU, there is limited evidence on which to base an
      assessment of best practices for providing high-quality end-of-life care in this
      setting. OBJECTIVE: To convene a Working Group of experts in critical care,
      palliative medicine, medical ethics, and medical law to address the question
      "What research needs to be done to improve end-of-life care to patients in the
      ICU?" METHODS: Participants were identified for membership in the Working Group
      by purposive sampling within the fields of critical care medicine and nursing,
      palliative medicine, and medical ethics; others were chosen to represent social
      work and hospital chaplains. Through a process of breakout and plenary sessions,
      the group identified important questions that need to be addressed in the areas
      of defining the problem, identifying solutions, evaluating solutions, and
      overcoming barriers. CONCLUSIONS: Outlining unanswered questions on end-of-life
      care in the ICU is a first step to providing the answers that will allow us to
      improve care to patients dying in the ICU. These questions also serve to focus
      clinicians and educators on the important areas for improving quality of care.

PMID- 11588472
TI  - Critical care delivery in the intensive care unit: defining clinical roles and
      the best practice model.

PMID- 11588474
TI  - Outcome prediction models for very elderly critically ill patients: a pathway to
      more compassionate care?

PMID- 11588475
TI  - A rose by any other name: cardiac output.

PMID- 11588476
TI  - Clarifying the infarct through the trauma of cardiac surgery with troponin I.

PMID- 11588477
TI  - Research agenda or (North) American cultural hegemony?

PMID- 11588478
TI  - Family stress in the intensive care unit.

PMID- 11588479
TI  - Complications of cervical spine surgery.

PMID- 11588480
TI  - Renal replacement therapy in intensive care: one size does not fit all.

PMID- 11588481
TI  - Tube feeding: new life for an old procedure.

PMID- 11588482
TI  - Neutrophils in acute respiratory distress syndrome: upregulated, uninhibited, or
      even both.

PMID- 11588483
TI  - Testosterone administration in male burn patients: the good, the bad, and the
      ugly.

PMID- 11588484
TI  - Chicken soup for the stomach.

PMID- 11588485
TI  - Therapeutic targets in acute respiratory distress syndrome: role of the
      artificial lung.

PMID- 11588486
TI  - Quantification of neurologic function.

PMID- 11588487
TI  - Paying attention to death.

PMID- 11588488
TI  - What is best for patients is best for the intensive care unit.

PMID- 11588489
TI  - Outcome in meningococcemia: a relationship between quantity and quality?

PMID- 11588490
TI  - Viral pneumonia and hemoptysis.

PMID- 11588493
TI  - Update on orbital trauma.
AB  - Several advances in orbital trauma are presented. From new techniques in
      radiologic imaging, the use of endoscopy, and new treatment indications for
      certain types of fractures. Many of these advances result in decreased morbidity
      and improved functional results in the treatment of orbital and periorbital
      trauma.

PMID- 11588494
TI  - Orbital and periorbital infections.
AB  - Infections of the orbit and periorbital tissues are not uncommon. Trauma, skin
      infections, and sinusitis are frequently the underlying cause. Studies have shown
      changes in epidemiology and pathogens in the last decade. Although classical
      manifestations are usually present, atypical cases without specific signs and
      symptoms may confound the diagnosis. A high index of suspicion, aided by
      ultrasonography, computed tomography, and magnetic resonance imaging, is
      frequently required for an accurate diagnosis. Prompt diagnosis and treatment may
      lead to resolution of the infection, thus avoiding ocular sequelae. Orbital
      infections may spread into the globe, causing endophthalmitis. Some patients may
      even need an enucleation or evisceration. New materials and techniques may
      improve the final result of an anophthalmic socket.

PMID- 11588495
TI  - Advances in imaging in oculoplastics.
AB  - Color Doppler imaging, computed tomography (CT) and magnetic resonance (MR)
      imaging are the most precious imaging tools for the clinician in the field of
      oculoplastics. Orbital and facial vasculature, with its dynamic changes and flow
      velocities seen in orbital varices, carotid-cavernous fistulas, and dural
      cavernous arteriovenous malformations, is best detected by Color Doppler imaging.
      Computed tomography remains the dominant imaging modality in the evaluation of
      orbital trauma. Helical CT axial scanning with multiplanar reconstruction and
      three-dimensional CT imaging are most helpful in assessing iatrogenic,
      traumatogenic, and teratogenic orbital abnormalities. Despite its poor histologic
      specificity, MR imaging provides superior soft tissue contrast, and contrast
      enhanced MR imaging has an established role regarding soft tissue tumor
      infiltration. The greatest value of MR studies in the evaluation of orbital and
      palpebral tumors is that it has the capacity to show the precise relation between
      lesions and adjacent structures before the clinician contemplates a surgical
      approach. Finally, contrast-enhanced MR imaging proved to be a valuable
      vascularization indicator based upon the extent of relative enhancement within
      porous orbital implant in anophthalmic socket.

PMID- 11588496
TI  - Graves ophthalmopathy.
AB  - Graves ophthalmopathy (GO) is an autoimmune disease that typically affects the
      thyroid gland and the orbit. The roles of the thyroid stimulating hormone
      receptor and cellular and humoral immunity in the pathogenesis of GO are being
      investigated. Investigators are gaining insights into the epidemiology of GO as
      it relates to other ocular and autoimmune diseases. Several possible tools for
      assessing GO disease activity are being studied. Medical and radiation therapy
      for GO recently have been evaluated prospectively. Orbital surgeons continue to
      refine orbital decompression techniques to improve patient outcomes and minimize
      surgical complications.

PMID- 11588497
TI  - Diseases of the lacrimal drainage system.
AB  - We will refer to lacrimal system pathologies involving the outflow pathways, as
      well as to the recent advances in the management of canalicular and lacrimonasal
      duct anomalies, including modifications to dacrycystorhinostomy technique,
      treatment for congenital obstructions, and lacrimal intubations. Special emphasis
      will be placed on the usefulness of nasal and canalicular endoscopy for the
      examination and treatment of congenital obstructions and endonasal pathologies,
      as an aid for intubations and lacrimal surgery, as well as on reasons for failed
      procedures.

PMID- 11588498
TI  - Lasers in oculoplastics.
AB  - In the past year, there have been many important advances in laser application in
      not only oculoplastics but also related fields such as dermatology and plastic
      surgery. This review article highlights advances in laser assisted lacrimal
      surgery with the adjunctive use of mitomycin C and the treatment of capillary
      hemangiomata with a tunable dye laser. There also have been advances in laser
      skin resurfacing, such as the combination of carbon dioxide and erbium:yttrium
      aluminum-garnet lasers to achieve improved results as well as the use of
      nonablative lasers. Lastly, physicians have achieved a greater understanding of
      the benefits and complications of combining laser resurfacing with other
      aesthetic procedures, such as lower blepharoplasty and facelifting.

PMID- 11588499
TI  - Amblyopia: detection, prevention, and rehabilitation.
AB  - This year's literature on the detection, prevention, and rehabilitation of
      amblyopia is again somewhat dominated by the topic of vision screening,
      specifically photoscreening and also by the therapeutic challenges of compliance
      and late treatment. Basic scientists also have added to our knowledge and
      understanding of certain interesting and clinically significant characteristics
      of the visual perception of amblyopes.

PMID- 11588500
TI  - Paralytic strabismus.
AB  - During the past year, many papers described new surgical approaches to correct
      extraocular muscles paralysis. New advances have been made in the knowledge of
      ptosis and superior oblique muscle myochymia. Moreover, the author reports
      sensory problems concerning subjective cyclorotation and binocularity that arise
      with macular translocation.

PMID- 11588501
TI  - Neuro-ophthalmologic manifestations of systemic disease and neurologic disease.

PMID- 11588502
TI  - Nystagmus.
AB  - This article reviews the recent literature on nystagmus and various aspects of
      the pathophysiology of congenital idiopathic nystagmus and nystagmus treatment.
      One paper shows a new classification of latent/manifest latent nystagmus based on
      eye movement recordings. Nystagmus associated with complex syndromes and with
      onset in childhood represents the subject of several important recent articles,
      as does acquired nystagmus. Nystagmus as a manifestation of the toxicity of
      pharmacological agents is becoming increasingly recognized. Important
      contributions have been made to the genetics of various forms of nystagmus that
      represent an essential feature of retinal diseases, such as congenital stationary
      night blindness, albinism, blue cone monochromatism, and achromatopsia.

PMID- 11588503
TI  - Transient relapses ("blips") of plasma HIV RNA levels during HAART are associated
      with drug resistance.
AB  - INTRODUCTION: In a large number of patients on HAART who achieved plasma HIV RNA
      levels below the limit of detection (50 copies/ml), transient relapses of HIV RNA
      levels ("blips") are observed. OBJECTIVE: To determine whether relapses of plasma
      HIV RNA during HAART are associated with development of drug resistance. METHODS:
      Plasma samples from 15 patients with a transient viral load relapse during HAART
      were studied. All regimens contained lamivudine (3TC). We used an ultrasensitive
      sequence approach to analyze the presence of drug resistance mutations during the
      relapse. RESULTS: The median plasma HIV RNA load of the relapse was 76 copies/ml
      (range 50-1239). In 11 of 15 cases, a genotype of HIV could be obtained.
      Mutations in the RT and protease gene conferring resistance to one or more drugs
      were observed in 8 of 11 patients, 6 of whom had the M184V substitution. During a
      median follow-up of 27 months after the relapse, plasma HIV RNA levels remained
      undetectable in 13 of 15 patients. CONCLUSIONS: Plasma HIV RNA blips during HAART
      can be associated with selection of drug-resistant HIV. This indicates that viral
      replication may occur during HAART, probably caused by a temporary decrease in
      active drug concentrations. A blip containing only wild-type virus is not
      necessarily caused by viral replication. In this situation the raise of HIV RNA
      could also originate from release of wild-type viruses, caused by activation of
      the latent virus reservoir. Independent of the mechanism, blips did not preclude
      successful inhibition of viral replication during 2-year follow-up in the
      majority of these cases.

PMID- 11588504
TI  - Low frequency of severe hepatotoxicity and association with HCV coinfection in
      HIV-positive patients treated with HAART.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) is strongly effective in
      reducing morbidity and mortality in HIV-1-positive individuals. Its main drawback
      is the potential toxicity. Data on the frequency and determinants of severe
      hepatotoxicity in a clinical setting are still sparse. METHODS: This is a
      prospective study of HIV-1-positive individuals with known HBsAg and HCV-Ab
      serology. The study end point was progression to alanine aminotransferase (ALT)
      levels > or =200 IU/L after HAART initiation. Cumulative probability of
      progression to this end point was estimated by the Kaplan-Meier method. Crude and
      adjusted hazard ratios (HR) were estimated by proportional hazards regression
      model. RESULTS: One thousand two hundred fifty-five patients were included. HBsAg
      was found in 91 (7.2%), HCV-Ab in 578 (46.5%) patients; almost all injection drug
      users (451 of 482; 93.6%) were HCV-Ab positive. Sixty-one individuals progressed
      to the end point with a probability of 7.9% (95% confidence interval [CI], 5.6
      10.0) of progression at 24 months from starting. Independent factors predicting
      progression to the end point were baseline ALT levels (HR, 5.29; 95% CI, 3.24
      8.65; every 10 IU/L higher), HCV-Ab positivity (HR, 4.01; 95% CI, 1.48-10.85) or
      both HBsAg and HCV Ab positivity (HR, 3.85, 95% CI, 1.01-14.61), and previous non
      HAART therapy (HR, 1.84, 95% CI, 1.04-3.42). Patients receiving stavudine
      containing regimens had a lower risk than those receiving zidovudine-containing
      regimens (HR, 0.30, 95% CI, 0.12-0.71). CONCLUSIONS: There was a low risk of ALT
      > or =200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at
      HAART initiation are important predictors of progression to ALT > or =200 IU/L;
      stavudine-containing regimens were associated with a lower risk compared with
      zidovudine-containing regimens.

PMID- 11588505
TI  - Antiretroviral regimen complexity, self-reported adherence, and HIV patients'
      understanding of their regimens: survey of women in the her study.
AB  - BACKGROUND: Research regarding treatment adherence in chronic diseases, such as
      hypertension, suggests that increasing complexity in the medication regimen is
      associated with decreasing patient adherence. However, less is known about the
      relationship between regimen complexity and adherence in the treatment of
      HIV/AIDS. OBJECTIVE: To examine the relationship between antiretroviral (ART)
      regimen complexity and patient understanding of correct regimen dosing to
      adherence (missing doses in the past 1 and 3 days). METHODS: Cross-sectional
      survey of a cohort of women living with HIV/AIDS and enrolled in the HER (HIV
      Epidemiologic Research) Study. RESULTS: Seventy-five percent of patients
      correctly understood the dosing frequency of their ART medications, 80%
      understood the food-dosing restrictions, whereas only 63% understood both. The
      percentage of patients with a correct understanding of dosing decreased with
      increasing regimen complexity (increased dosing frequency and food-dosing
      restrictions). Patients were more likely to have missed doses in the previous 3
      days if they were taking ART medications three or more times per day or had to
      take one or more antiretrovirals on an empty stomach. A multivariate logistic
      regression model demonstrated that patients with less complex regimens (twice
      daily or less in frequency, no food-dosing restrictions) who correctly understood
      the dosing and food restrictions of their ART regimen were less likely to have
      skipped doses in the past three days (odds ratio [OR], 0.4; 95% confidence
      interval [CI], 0.2-0.7) than those with more complex regimens. Younger age and
      higher CD4 count were also associated with a reduced likelihood of skipping
      doses. No association was found between adherence and race/ethnicity, current or
      past injection drug use, or education. CONCLUSIONS: Self-reported adherence is
      better among patients with less complex ART regimens. This is in part because
      patients' understanding of regimen dosing decreases as regimen complexity
      increases. Therefore, simplifying antiretroviral regimens may have an important
      role in improving patients' adherence.

PMID- 11588506
TI  - Feeding mode, intestinal permeability, and neopterin excretion: a longitudinal
      study in infants of HIV-infected South African women.
AB  - Exclusive breast feeding has been associated with a lower rate of mother-to-child
      HIV transmission than breast feeding plus other foods. To obtain further
      information on biologic outcomes of different feeding modes, we examined 272
      infants of HIV-infected South African women at ages 1, 6, and 14 weeks. At each
      visit information about infant diet and morbidity was collected and infants
      underwent a lactulose/mannitol dual sugar intestinal permeability test. In a
      subset of infants, urinary neopterin excretion was measured as an indicator of
      immune system activation. Infants who had themselves become HIV-infected by 14
      weeks had higher ( p <.01) intestinal permeability at 6 and 14 weeks and slightly
      (.05 < p <.1) higher neopterin excretion at all times than uninfected infants. At
      1 week infants given no breast milk had higher ( p <.05) intestinal permeability
      than infants given breast milk exclusively or with other foods. Intestinal
      permeability in infants fed breast milk plus other foods was never increased
      relative to that of exclusively breastfed infants. Feeding mode had no effect on
      neopterin excretion. Thus, infant HIV infection induces changes in gut
      permeability and possibly immune system activation before clinical symptoms
      become apparent. The effects of feeding mode on infant intestinal permeability or
      urinary neopterin excretion do not explain a possible protective effect of
      exclusive breast feeding on mother-to-child transmission of HIV.

PMID- 11588507
TI  - The effect of insurance coverage changes on drug utilization in HIV disease.
AB  - BACKGROUND: Insurance coverage facilitates access to life-saving medications for
      many patients with HIV disease. Thus, the effects of insurance coverage changes,
      such as the gain or loss of coverage, may be important in explaining patient
      access and adherence to the medications used in the treatment of HIV disease.
      OBJECTIVES: The study's objective was to examine whether changes in health
      insurance coverage affect rates of prescription drug use by patients with HIV
      disease. METHODS: Data were ascertained from adults participating in a series of
      up to six interviews as part of the AIDS Costs and Services Utilization Survey
      (ACSUS). ACSUS was an 18-month panel survey of patients in care for HIV/AIDS at
      26 sites located in 10 U.S. cities. Poisson regression analyses with generalized
      estimating equations were conducted to determine the effects of demographic and
      socioeconomic variables on the acquisition rate of antiretrovirals,
      antipneumocystics, and antidepressants. The analytic sample consisted of 1566
      respondents who provided 6518 interviews. RESULTS: Although changes in insurance
      coverage were common, complete loss of insurance was reported in only 1.5% of the
      interviews whereas gaining insurance was reported in 3.3% of interviews. Having
      no coverage was associated with significantly lower rates of antiretroviral (rate
      ratio [RR], 0.73), antipneumocystic (RR, 0.58) and antidepressant use (RR, 0.31).
      Gaining insurance coverage was associated with lower antiretroviral (RR, 0.75)
      and antipneumocystic (RR, 0.70) use whereas losing insurance was associated with
      lower antiretroviral use (RR, 0.58). In multivariate analyses, these associations
      remained. CONCLUSIONS: Changes in health insurance coverage are associated with
      lower rates of drug use for some medications used by patients with HIV disease.

PMID- 11588508
TI  - Tolerability of enteric-coated didanosine capsules compared with didanosine
      tablets in adults with HIV infection.
AB  - BACKGROUND: A new enteric-coated (EC) didanosine (ddI) formulation (Videx EC;
      Bristol-Myers Squibb, Princeton, NJ, U.S.A.) may be better tolerated than the
      tablet form because it lacks the buffer component thought to be responsible for
      diarrhea and other gastrointestinal (GI) side effects. OBJECTIVE: To evaluate the
      frequency and magnitude of GI side effects (nausea, bloating, GI upset, diarrhea,
      abdominal cramps, gas [flatus]) before and after switching the formulation of
      ddI, in study subjects who were experiencing one or more GI symptom(s) of at
      least moderate severity. METHODS: A 6-week open label crossover study of current
      didanosine tablet users comparing daily symptom scores (7 point scale, 0 = absent
      to 6 = very severe) during weeks 1 to 2 (on tablets) to weeks 4 and 6 (on EC
      capsules). Formulation palatability and preference, lifestyle effects, and use of
      antidiarrheals or other medications for symptom relief were also assessed.
      RESULTS: GI symptom scores (7-day means) on tablets were diarrhea 2.11, gas 2.00,
      bloating 1.23, abdominal cramps 0.74, GI upset 0.69, nausea 0.66. After switching
      to EC (week 4 and week 6), mean scores decreased for diarrhea (mean scores 0.99
      week 4, 0.79 week 6), gas (0.95, 0.79), bloating (0.49, 0.32), abdominal cramps
      (0.21, 0.05), GI upset (0.16, 0.14), and nausea (0.32, 0.22). Severity of all GI
      symptoms was significantly reduced after 4 weeks on EC capsules ( p <.01 by
      paired t- test). Negative impact of side effects on routine activities was
      significantly reduced (41% on tablet vs. 7% on EC; p <.01). All 42 study subjects
      preferred the EC form. CONCLUSIONS: According to patients' diary scores,
      switching to ddI in EC form significantly reduces nausea, bloating, GI upset,
      diarrhea, abdominal cramps, and gas for individuals who experienced GI side
      effects while taking the buffered tablet form. The striking tolerability
      advantages appear to support routine switching to EC for such patients and may
      suggest that widespread preferential selection of the EC form is appropriate to
      enhance didanosine tolerability and promote treatment adherence.

PMID- 11588509
TI  - HIV-1 induction-maintenance at the lymph node level: the "Apollo-97" Study.
AB  - OBJECTIVE: To assess the effects of five-drug combination therapy on HIV-1 load
      in lymph nodes and subsequent maintenance with four and three drugs. METHODS: Ten
      pharmacotherapeutically naive patients received a combination of zidovudine,
      lamivudine, didanosine, ritonavir, and saquinavir for 24 weeks, then zidovudine,
      lamivudine, didanosine, and saquinavir for the next 24 weeks, and finally
      zidovudine, lamivudine, and saquinavir for the last 24 weeks. HIV-1 RNA in lymph
      nodes was measured using quantitative polymerase chain reaction (PCR) at
      baseline, after 12, 24, 48, and 78 weeks. Plasma HIV-1 RNA, proviral DNA in
      peripheral blood mononuclear cells (PBMCs), circulating lymphocyte subsets, and
      protease inhibitor levels in blood were also regularly measured. Genotypic
      resistance was assessed in the different compartments in 2 patients who were
      failed by therapy. RESULTS: HIV-1 RNA decreased in lymph nodes in 9 patients and
      was stable in 1 despite initial control of plasma replication <20 copies/ml in
      each patient. Lymph node levels rebounded in 1 patient at week 72 as a result of
      lack of adherence and remained stable in the 8 others despite maintenance
      regimens. This represents a mean drop of -3.17 log in lymph nodes for the 8
      patients maintaining undetectable viremia at 72 weeks. In the patient with stable
      lymph node viral RNA, selection of the M184V mutation was demonstrated at this
      level before detection in plasma and low blood saquinavir levels were found
      throughout the study. Continuous improvements in immune parameters were observed
      in all cases, although PBMC proviral DNA levels either showed a continuous
      decrease or stabilized to a plateau. CONCLUSIONS: More complex regimens do not
      perform better in lymph nodes than classic triple therapy. The persistence of HIV
      1 RNA in lymph nodes could be related with cellular resistance mechanisms rather
      than an insufficient potency of the regimens.

PMID- 11588510
TI  - Is the time from HIV seroconversion a determinant of the risk of AIDS after
      adjustment for updated CD4 cell counts?
AB  - OBJECTIVE: To evaluate the effect of time from seroconversion to a given CD4 cell
      count on progression to AIDS after that count after adjusting for updated CD4
      cell counts. METHODS: Using pooled data from 19 seroconverter cohorts, we
      examined the association between the time from a CD4 <500 cells/mm 3, (<350,
      <200) to the first AIDS-defining event and time from seroconversion to that CD4
      threshold. We adjusted for age, gender, exposure category, and HIV test interval
      in Cox models stratified by cohort. We estimated the residual effect of time from
      seroconversion, adjusting for updated CD4 cell counts. A cause-specific competing
      risks model was then used to evaluate this residual effect on progression to each
      AIDS-defining disease. Analyses were censored on December 31, 1995. RESULTS: Of
      3825, 3006, and 1804 individuals reaching CD4 thresholds of 500, 350, and 200,
      respectively, 1274, 1192, and 985, respectively, developed AIDS. We found a
      significant effect of time from seroconversion on the risk of AIDS even after
      adjusting for updated CD4 counts. For individuals reaching a CD4 threshold of 350
      cells/mm 3, a 1-year increase from seroconversion was associated with an increase
      in risk of AIDS of 6% (3%-9%) ( p =.01). This effect appeared to be nonlinear. In
      the first 4 years, a 1-year increase from seroconversion was associated with an
      11% increase in the risk of AIDS, but there was no apparent increase in risk
      after 4 years. The residual effect of time from seroconversion was significantly
      heterogeneous ( p =.002), with respect to the risk of individual AIDS-defining
      diseases. Findings were similar for CD4 thresholds of 500 and 200 cells/mm 3,
      respectively. CONCLUSIONS: We found a small, statistically significant, residual
      effect of time from seroconversion on the risk of AIDS. In practical terms, when
      considering an infected individual's risk of AIDS from a given CD4 cell count,
      there is little to be gained from knowing the time of seroconversion. However,
      this effect differs significantly among specific AIDS-defining diseases.

PMID- 11588511
TI  - Determinants of high-risk sexual behavior among immigrant groups in Amsterdam:
      implications for interventions.
AB  - OBJECTIVES: To determine predictors for sexual risk behavior among immigrant men
      in Amsterdam. METHODS: From May 1997 to July 1998, 650 men from Surinam, the
      Antilles, and Ghana were recruited by convenience sampling. Multivariate logistic
      regression was used to find independent predictors for 1) multiple sex partners
      (>sexual 1 partner in the past year), 2) unprotected sex with casual partners in
      The Netherlands, 3) sexual activity in country of origin, and 4) unprotected sex
      in country of origin. RESULTS: 1) Multiple sex partners were reported by 50% of
      respondents. Independent predictors were a recent infection with a sexually
      transmitted disease (STD), youth, low educational level, Afro-Surinamese origin,
      lack of a long-term relationship and history of commercial sex contact. 2)
      Unprotected sex occurred in 24% of casual partnerships. Independent predictors
      were a recent STD infection, low educational level, use of hard drugs, age
      between 20 and 29, few sexual partners, unprotected sex in country of origin, and
      a partner from the respondent's ethnic group. 3) During the past 5 years, 24%
      were sexually active in country of origin. Independent predictors were Ghanaian
      origin, age over 20, a relatively high income, and multiple partners. 4)
      Unprotected sex occurred in 39% of the partnerships in country of origin.
      Independent predictors were low educational level, history of STDs, lack of
      health insurance, Ghanaian origin, frequent visits to home country, few sexual
      partners, and unprotected sex with casual partners in The Netherlands.
      CONCLUSION: Among immigrant men in Holland, important target groups for AIDS
      prevention programs have been identified. Men who visit their country of origin
      should be made aware of the risk of sexual contact with local women. Furthermore,
      it should be taken into account that immigrant men use condoms less frequently
      with women of their own ethnic group than with Dutch women.

PMID- 11588512
TI  - A global review of legislation on HIV/AIDS: the issue of HIV testing.
AB  - OBJECTIVE: Critical review of worldwide legislation on HIV/AIDS, with a focus on
      the issue of HIV testing, mainly in a military context. DESIGN: Analysis of
      health legislation on HIV/AIDS among 121 of the 191 member states of the World
      Health Organization (WHO), representing 85% of the world's population. METHODS:
      The WHO Directory of Legal Instruments Dealing with HIV Infection and AIDS has
      been the main source consulted. Relevant findings of two global surveys were used
      to examine HIV testing in the military. RESULTS: AIDS cases are reportable in 60%
      of the 121 countries, whereas HIV infections in no more than 26%. Notifications
      are kept confidential by law in 20% of countries. Only 17% have developed HIV
      specific legislation against social discrimination, whereas 10% have passed
      legislation establishing financial reimbursement to those who have acquired HIV
      infection after injection of HIV-contaminated biologic material, support for
      occupational risk, and/or social protection for patients. Only 42% of the 121
      countries report having legal instruments that require screening of donated
      blood. Legislative measures that address, generally in a prescriptive but
      sometimes also in a protective way, vulnerable groups, such as commercial sex
      workers, men who have sex with men, injecting drug users, and recipients of
      multiple transfusions of blood or blood-derivatives, are reported in 27% of
      countries. Other categories considered potentially vulnerable, for which specific
      legislation has been passed, include immigrants (17% of countries), prisoners
      (5%), and health personnel (14%). Further legislative measures for HIV prevention
      address testing pregnant women in the prenatal period (7% of countries),
      supporting condom promotion (11%), measures requiring quarantine, isolation, or
      coercive hospitalization of HIV-infected people or AIDS patients (9%), or
      imposing penal sanctions for HIV-infected people who deliberately expose others
      to the risk of transmission (10%). A National AIDS Committee responsible for
      addressing issues related to HIV/AIDS has been established by law in 39% of the
      121 countries. Global surveys show that 27 countries carry out compulsory HIV
      screening on recruitment of military personnel. CONCLUSIONS: These data represent
      a useful tool to make governments aware of the problem of underreporting of legal
      instruments to the WHO and of the need to promote legislation in line with the
      idea that public health and human rights are complementary, not conflicting,
      goals.

PMID- 11588513
TI  - Women's willingness to participate in microbicide trials in Northern Thailand.
AB  - To assess women's interests and concerns regarding participation in trials of
      microbicides in Chiang Rai, Thailand, we administered structured questionnaires.
      Before answering the questionnaire, women attended an educational session on
      microbicides and clinical trials. Of 370 participants, 82% correctly answered 8
      or more of the 11 overall comprehension questions, indicating an adequate
      knowledge base among the women from which to answer questions about attitudes
      toward microbicide trials. The most common motivations for participating in a
      trial were "getting tested for HIV" and "doing something good for women's
      health." The greatest barrier to participation was women's fear that if they
      proposed use of a microbicide, their husbands might feel protected and thereby
      have more sex partners. Overall, 6.2% said they would be "definitely willing to
      participate," and 66.8% said they wanted to participate but wanted to think about
      it. Most women previously unacquainted with the concept of microbicides or
      clinical trial design displayed adequate knowledge of these subjects after the
      short educational session. If women's initial reactions are validated by actual
      willingness, surveys could prove valuable for selecting sites for microbicide
      trials, estimating enrollment rates, and tailoring trials to make them most
      acceptable to women.

PMID- 11588514
TI  - Longitudinal patterns of sexual behavior and condom use in a cohort of HIV
      negative gay and bisexual men in Vancouver, British Columbia, Canada, 1995-2000.
AB  - OBJECTIVE: To characterize longitudinal patterns of sexual behavior in a cohort
      of young gay and bisexual men and determine their reasons for not using condoms.
      METHODS: Prospective data from a cohort of young gay and bisexual men aged 18 to
      30 years were studied. Study participants had completed a baseline questionnaire
      and HIV test between May 1995 and April 1996 and four annual follow-up
      questionnaires. RESULTS: A total of 130 HIV-negative Vanguard participants met
      the eligibility criteria for this analysis. The median age at baseline was 26
      years (range, 24-28). Most were white (79%), had completed high school (85%),
      were currently employed (82%), lived in stable housing (95%), and reported annual
      incomes of > or =$10,000 (82%). (All dollar amounts are given in Canadian
      dollars.) Consistently over the 5-year study period, > 70% of study subjects
      reported having > or =1 regular male sexual partners in the previous year. During
      each of the five successive 1-year periods, between 34% and 40% of respondents
      reported having had unprotected receptive anal intercourse with regular partners.
      Slightly fewer individuals (between 29%-39%) reported having had unprotected
      insertive anal intercourse with regular partners. Between 13% and 25% of
      participants reported having had insertive unprotected anal intercourse with
      casual sexual partners; and between 9% and 18% reported having had unprotected
      receptive anal intercourse with casual sexual partners. Reasons for engaging in
      unprotected anal intercourse varied depending on type of sexual partnership.
      CONCLUSION: High-risk sexual behaviors remained fairly consistent over a 5-year
      period in this study. This suggests that it is critically important to understand
      the motivations for unprotected sex when designing and implementing programs
      aimed at reducing HIV risk among young gay and bisexual men.

PMID- 11588515
TI  - Impact of human immunodeficiency virus type 1 subtype on HIV antibody detection
      in Burkina Faso.

PMID- 11588516
TI  - Opportunistic infection prophylaxis in the women's interagency HIV study (WIHS).

PMID- 11588517
TI  - Potential adverse effects of structured therapeutic interruptions on the pool of
      HIV-infected cells.

PMID- 11588518
TI  - Inhibition of HIV replication by A77 1726, the active metabolite of leflunomide,
      in combination with pyrimidine nucleoside reverse transcriptase inhibitors.

PMID- 11588519
TI  - Signaling pathway and chronotropic action of parathyroid hormone in isolated
      perfused rat heart.
AB  - Parathyroid hormone (PTH) activates both adenylyl cyclase and phospholipase C via
      the PTH-1 receptor. We previously reported that PTH increased heart rate and that
      this effect was mediated via the pacemaker current (I f ). However, it has been
      reported that PTH exerts its chronotropic effect via an interaction with
      adrenergic receptors or via L-type calcium channels. Thus, the objective of the
      study was to elucidate the exact mechanism of the chronotropic effect of PTH. We
      tested whether its chronotropic effects could be abolished by inhibitors of the
      following systems in isolated perfused rat hearts: alpha-adrenergic (prazosin);
      beta-adrenergic (propranolol); angiotensin II (CV11974); endothelin-1 (TAK044);
      calcium channel (verapamil); adenylyl cyclase (miconazole); phospholipase C
      (U73122) or I f (CsCl). In addition, we measured the cyclic adenosine
      monophosphate level of the heart after PTH administration. Whereas prazosin,
      propranolol, CV11974, TAK044, verapamil, and U73122 did not inhibit the
      chronotropic effect of PTH, CsCl or miconazole suppressed it significantly. PTH
      increased the cyclic adenosine monophosphate level of the atrium but not the left
      ventricle. These results indicate that the chronotropic actions of PTH are
      mediated via selective activation of adenylyl cyclase to increase the I f
      current.

PMID- 11588520
TI  - Beneficial effects of amiodarone and dronedarone (SR 33589b), when applied during
      low-flow ischemia, on arrhythmia and functional parameters asssessed during
      reperfusion in isolated rat hearts.
AB  - The effects of short-term amiodarone and dronedarone treatments on action
      potential characteristics and arrhythmia (ventricular tachycardia ) induced by
      reperfusion after global low-flow ischemia were studied in rat hearts. The
      actions of amiodarone and SR on recovery of coronary flow and contractile
      function were also determined. Isolated hearts were stabilized for 40 min and
      were then submitted to 25-min global low-flow ischemia (constant coronary flow,
      0.3 ml/min) followed by 30 min of reperfusion at constant pressure. Drugs were
      applied only during ischemia: consequently, action potential duration (APD)
      tended to widen. During reperfusion, APD tended to recover or shorten, and the
      more complete the recovery, the less the arrhythmia. Despite its ability to widen
      APD during ischemia, amiodarone facilitated APD recovery during reperfusion.
      Moreover, APD shortening and ventricular tachycardia suppression exhibit a bell
      shaped concentration-response relation, implying that the drugs affect
      ventricular tachycardia by a class III-independent action. These results point to
      an anti-ischemic action supported by improvement in function and inhibition of
      reactive hyperemia.

PMID- 11588521
TI  - Ethanol-induced reduction in myocardial oxygen consumption can be attenuated by
      inhibiting guanylyl cyclase.
AB  - We tested the hypothesis that low-dose ethanol-induced reductions in myocardial
      metabolism were related to increased cyclic guanosine monophosphate (GMP).
      Anesthetized open chest rabbits were divided into four groups: control (Ringers
      lactate and vehicle), ETOH (250 mg/kg i.v. ethanol and vehicle), ODQ (Ringers
      lactate and 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ 10(-4) M ), and
      ETOH-ODQ (ethanol and ODQ). ODQ, a soluble guanylyl cyclase inhibitor, or vehicle
      was applied topically to the epicardium for 15 min, while either Ringers lactate
      or ethanol was administered intravenously. Oxygen consumption (VO2 ) in both the
      subepicardium (EPI) and subendocardium (ENDO) was determined from coronary blood
      flow (radioactive microspheres) and O2 extraction (microspectrophotometry).
      Cyclic GMP was determined by radioimmunoassay. ETOH significantly decreased VO2
      in the subepicardium (9.2 +/- 1.0-5.6 +/- 0.7 ml O2 /min/100 g) and
      subendocardium (9.7 +/- 0.8-7.1 +/- 0.8) and increased cyclic GMP in the
      subepicardium (10.2 +/- 1.7-13.8 +/- 0.8 pmol/g) and subendocardium (11.0 +/- 0.5
      13.7 +/- 0.9). With ODQ, there was no significant change in the subepicardial
      (9.5 +/- 1.3) or subendocardial (9.0 +/- 0.9) VO2. However, ODQ caused a
      significant increase in both wall thickening (12.9 +/- 0.9-17.2 +/- 1.2%) and
      maximal rate of change in wall thickness (10.8 +/- 0.9-16.3 +/- 1.9 mm/s) and
      decreased subepicardium (8.3 +/- 1.3) and subendocardium (7.8 +/- 1.2) cyclic
      GMP. The ETOH-ODQ group had cyclic GMP (subepicardium 9.0 +/- 1.8, subendocardium
      8.6 +/- 2.4) and VO2 (subepicardium 7.9 +/- 0.5, subendocardium 8.4 +/- 0.4)
      values similar to control. Thus, the ethanol-induced rise in cyclic GMP was
      associated with a decrease in myocardial O2 consumption. When this rise was
      blocked with a soluble guanylyl cyclase inhibitor, the reduction in metabolic
      demand was also eliminated. This demonstrated that the alcohol-induced reduction
      in myocardial metabolism was related to increased cyclic GMP and suggests a novel
      mechanism for the effect of ethanol.

PMID- 11588522
TI  - Do arterial effects of antihypertensive drugs depend on subject's serum
      cholesterol?
AB  - Effects of antihypertensive treatment on large arteries may be influenced by the
      type of drug and concomitant risk factors such as blood cholesterol. To explore
      these possibilities we investigated the common carotid artery of 20 subjects with
      low cholesterol and 19 subjects with high cholesterol, all with essential
      hypertension, randomly allocated to 3 months of treatment with nitrendipine (20
      mg/d) or trandolapril (2 mg/d). Carotid parameters were determined by recording
      instantaneous pressure (applanation tonometry) and diameter (echotracking device)
      and by modeling the pressure-diameter loop to obtain the Peterson modulus,
      stiffness index, measured and isobaric compliances, and wall viscosity. Effects
      of drugs on carotid parameters did not differ, except on systolic and diastolic
      diameters (p < 0.01), which increased insignificantly under nitrendipine but
      decreased (p < 0.01) under trandolapril. Blood cholesterol status did not
      influence carotid effects of trandolapril, whereas patients with low and high
      cholesterol treated with nitrendipine exhibited significant differences in drug
      effects on (a) systolic and pulse pressures (p < 0.05), which decreased in
      patients with low cholesterol (p < 0.01, p < 0.05) but not in those with high
      cholesterol; (b) diastolic diameter (p = 0.05), which increased insignificantly
      in patients with low cholesterol but was unchanged in those with high
      cholesterol; and (c) wall viscosity (p < 0.01), which decreased in patients with
      low cholesterol (p < 0.05) but increased insignificantly in those with high
      cholesterol. Also, wall viscosity change under nitrendipine was positively
      related to the baseline blood cholesterol ( r = 0.64, p < 0.01). Thus,
      nitrendipine and trandolapril show noteworthy differences in their effects on the
      carotid artery, in particular with respect to the status of blood cholesterol,
      but these differences should be confirmed by larger studies.

PMID- 11588523
TI  - Relation of cyclic nucleotide ratios to ischemic and reperfusion injury in nitric
      oxide-donor treated rat hearts.
AB  - Nitric oxide (NO) donors given during ischemia possibly protect the myocardium by
      increasing tissue cyclic guanosine monophosphate (cGMP) and decreasing cytosolic
      Ca2+ levels. However, NO donors also elevate ischemic cyclic adenosine
      monophosphate (cAMP) levels, which exacerbates ischemic-reperfusion injury. The
      authors propose that suppression of this NO donor-induced increase in cAMP would
      improve the cardioprotective properties of these compounds. Langendorff perfused
      rat hearts were treated with sodium nitroprusside (SNP, 0.1 mM ) or glyceryl
      trinitrate (GTN, 1.0 microM ) and/or adenylyl cyclase (SQ, 50 microM ) or
      guanylyl cyclase (ODQ, 30-300 microM ) inhibitors during 40-min low-flow (0.2
      ml/min) ischemia. Control reperfusion rate-pressure product (RPP) recoveries were
      47 +/- 3% (n = 9) and improved to 59 +/- 1% (n = 11) (p < 0.05) with SNP
      treatment. Ischemic ODQ treatment decreased RPP recovery to 33 +/- 3% (n = 10) (p
      < 0.05). ODQ eliminated the cardioprotective effects of SNP (RPP recovery: 40 +/-
      5% [n = 7] vs. 59 +/- 1% [p < 0.05]). Adenylyl cyclase inhibition improved RPP
      recovery from 59 +/- 1% (SNP) to 72 +/- 4% (SNP + SQ) (n = 11) (p < 0.05). The
      authors conclude that (a) suppression of the NO donor-induced elevations in
      ischemic cGMP levels (ODQ) worsened reperfusion RPP, (b) suppression of the NO
      donor-induced elevation in ischemic cAMP levels (SQ) further improved reperfusion
      RPP in NO donor-treated hearts, and (c) the severity of ischemic-reperfusion
      injury in the NO donor-treated heart was inversely related to ischemic-tissue
      cGMP levels and often directly related to the ischemic-tissue cAMP-to-cGMP ratio.

PMID- 11588524
TI  - Activation of Erk mitogen-activated protein kinase proteins by vascular serotonin
      receptors.
AB  - We previously demonstrated that 5-hydroxytryptamine 2A (5-HT 2A ) receptor
      mediated rat arterial contraction was dependent on activation of tyrosine
      kinases, including mitogen-activated protein kinase (MAPK) kinase. In the current
      study, we examined arterial smooth muscle for the presence of serotonin (5
      hydroxytryptamine, 5-HT) 5-HT 1B, 5-HT 1D, 5-HT 1F, 5-HT 2A, 5-HT 2B, and 5-HT 7
      receptor mRNA and hypothesized that, if present, activation of these receptors
      would stimulate the extracellular signal-regulated kinase (Erk) MAPK pathway and
      an Erk MAPK-dependent contraction. RT-PCR analyses of rat aortic smooth muscle
      cells, cultured and fresh, indicated the presence of 5-HT 1B, 5-HT 1D, 5-HT 1F, 5
      HT 2A, 5-HT 2B, and 5-HT 7 receptor mRNA. The 5-HT 1B agonists RU24969 and
      CGS12066B, 5-HT 1B/1D/1F receptor agonist sumatriptan, and 5-HT 2B receptor
      agonist BW723C86 (10(-9) - 10(-4) M ) did not contract the aorta, nor did the 5
      HT 7 receptor antagonist LY215840 leftward shift 5-HT-induced contraction. The 5
      HT 1E/1F receptor agonist BRL54443 induced contraction, but this was abolished by
      the 5-HT 2A/2C receptor antagonist ketanserin (10 nM ); contraction was not
      observed with a different 5-HT 1F receptor agonist, LY344864. 5-HT and alpha
      methyl-5-HT produced a concentration-dependent increase in Erk MAPK activity in
      cultured aortic smooth muscle cells and in aorta contracted with these agonists.
      All other agonists were inactive; a high concentration of BRL54443 (10 microM )
      stimulated Erk MAPK activation (150% basal). Thus, while mRNA and possibly
      protein for multiple 5-HT receptors are present in aortic smooth muscle, only the
      5-HT 2A receptor plays a significant role in directly modulating contractility
      and activating the Erk MAPK pathway.

PMID- 11588525
TI  - Increased contribution of L-arginine-nitric oxide pathway in aorta of mice
      lacking the gene for vimentin.
AB  - Experiments were designed to investigate endothelial function in the aorta of
      mice lacking the gene for the cytoskeleton protein vimentin (vim -/- ). Rings
      with and without endothelium from wild-type (vim +/+ ), heterozygous (vim +/- ),
      and homozygous (vim -/- ) mice were suspended in organ chambers to record of
      changes in isometric tension. During phenylephrine contraction, acetylcholine
      evoked comparable endothelium-dependent relaxations in the three groups. In the
      presence of Nomega-nitro-L-arginine, acetylcholine caused endothelium-dependent
      contractions, which were greater in vim -/- than in vim +/+ and vim +/- aortas.
      Indomethacin did not affect relaxation to acetylcholine in vim +/+ or in vim +/-,
      but it significantly increased the maximal response in vim -/- (67 +/- 7 vs. 102
      +/- 4%). Response to acetylcholine in vim -/- aortas was not affected by
      cyclooxygenase type 2 inhibitor NS-398, the thromboxane receptor antagonist SQ
      29,548, or superoxide dismutase. Relaxations to sodium nitroprusside were not
      different between vim +/+ and vim -/- mice and were not affected by
      cyclooxygenase inhibition. Cyclic guanosine monophosphate levels, which were
      increased to a comparable level by acetylcholine in vim +/+ and vim -/-, were
      augmented by indomethacin in vim -/- aortas but not in vim +/+ aortas. Expression
      of endothelial nitric oxide synthase was not different between vim +/+ and vim -/
      preparations. These results suggest that despite comparable endothelium
      dependent responses to acetylcholine, endothelial cells from vim -/- mice release
      a cyclooxygenase product that compensates the augmented contribution of nitric
      oxide.

PMID- 11588526
TI  - Effect of lipid-lowering therapy with pravastatin on myocardial blood flow in
      young mildly hypercholesterolemic adults.
AB  - Serum low-density lipoprotein cholesterol concentration is an important regulator
      of vascular reactivity. This double-blinded study examined the effect of lipid
      lowering therapy on myocardial vasodilatory function in young
      hypercholesterolemic but otherwise healthy men. Fifty-one men (age 35 +/- 4
      years) with mild hypercholesterolemia (total cholesterol, 5.6 +/- 0.8 mM ) were
      randomly assigned to receive pravastatin, 40 mg/day, or placebo for 6 months.
      Myocardial blood flow was measured at rest and during adenosine-induced hyperemia
      using positron emission tomography and oxygen-15-labeled water at baseline and
      after treatment. Pravastatin lowered low-density-lipoprotein cholesterol by 33%
      from 3.77 +/- 0.76 mM (p < 0.001), whereas placebo had no effect. At baseline,
      resting and adenosine-induced flow values were 0.85 +/- 0.27 and 3.61 +/- 1.00
      ml/min per gram in the pravastatin group and 0.83 +/- 0.18 and 3.17 +/- 0.69
      ml/min per gram in the placebo group. Despite significant low-density-lipoprotein
      cholesterol lowering, resting and adenosine-stimulated blood flow values remained
      similar at follow-up: 0.86 +/- 0.23 and 3.79 +/- 1.31 vs. 0.78 +/- 0.20 and 3.20
      +/- 0.86 ml/min per gram, in the pravastatin and placebo groups, respectively. An
      improvement in adenosine-induced flow after pravastatin, but not after placebo,
      was seen only in a subgroup of subjects (n = 15) with relatively low adenosine
      flow (<4.0 ml/min per gram) at baseline. Six months of cholesterol-lowering
      therapy with statin treatment has no overall significant effect on coronary
      vasodilator capacity in healthy subjects with mildly elevated cholesterol levels.
      A controlled study is needed to further test whether improvement in coronary
      function is obtained in subjects with initially reduced hyperemic flow response.

PMID- 11588527
TI  - Vascular responses to endothelin-1, angiotensin-II, and U46619 in glycerol
      induced acute renal failure.
AB  - Angiotensin II and endothelin-1, major endogenous vasoconstrictors in acute renal
      failure (ARF), can modulate the effects of each other. This study aimed to
      evaluate the interaction between these vasoconstrictors in glycerol-induced ARF
      by evaluating their effects in the isolated perfused kidney in the presence of
      their respective antagonists. In ARF, angiotensin II (2.5-25 ng) caused an
      increase in perfusion pressure. Saralasin, 1 microM, a nonselective angiotensin
      receptor antagonist, reduced these responses by 61+/- 6% (p < 0.05).
      Surprisingly, SQ29548, 1 microM, a selective PGH2 /thromboxane A2 receptor
      blocker, also reduced angiotensin II responses (62 +/- 4%; p < 0.05). BQ610 1
      microM, an ETA -selective receptor antagonist, was without effect, but BQ788 1
      microM, an ETB -selective antagonist, attenuated the response by 70 +/- 4% (p <
      0.05). In ARF, in contrast to angiotensin II, vasoconstriction by endothelin-1 (5
      25 ng) was diminished. Saralasin further attenuated endothelin-1 response by 65
      +/- 2% (p < 0.05), whereas SQ29548 was without effect. BQ788 reduced the
      responses by 67 +/- 7% (p < 0.05), whereas BQ610 was without effect (42 +/- 30%;
      p > 0.05). BQ610 and BQ788 combination further reduced vasoconstriction by 89 +/-
      3% (p < 0.05). Responses to U46619 were not changed in ARF. However, saralasin
      and BQ788, but not BQ610, attenuated its vasoconstrictor action. We conclude that
      vascular responses in ARF may be attributed to enhanced responses to angiotensin
      II through activation of ETB and/or PGH2 /thromboxane A2 receptors. We also
      suggest that the vasoconstrictor response to endothelin-1 in ARF is predominantly
      ETB receptor-mediated.

PMID- 11588528
TI  - T-lymphocyte and plasma angiotensin-converting enzyme activity during enalapril
      and losartan administration in humans.
AB  - This study evaluated the long-term effects of the angiotensin-converting enzyme
      inhibitor enalapril and the angiotensin II type 1 receptor antagonist losartan on
      the angiotensin-converting enzyme activity in T lymphocytes and plasma in
      patients with essential hypertension. The study was a randomized, placebo
      controlled, double-blind, crossover design. Nine patients with sitting blood
      pressure > or = 95 mm Hg and < or = 105 mm Hg at the end of a 4-week placebo run
      in period entered the double-blind phase of the study, which consisted of three 6
      week periods during which patients were treated with placebo, enalapril (20 mg,
      once daily), or losartan (50 mg, once daily) The angiotensin-converting enzyme
      activity in T lymphocytes was measured as the activity of the degradation of the
      substrate Hippuryl-His-Leu and as the appearance of the dipeptide His-Leu, which
      was quantified spectrofluorometrically. Enalapril but not losartan suppressed (p
      < or = 0.01) the angiotensin-converting enzyme activity in plasma, whereas it
      stimulated (p < or = 0.05) the angiotensin-converting enzyme activity in
      circulating T lymphocytes. Our data document induction of angiotensin-converting
      enzyme in human T lymphocytes during long-term treatment with the angiotensin
      converting enzyme inhibitor enalapril. Angiotensin II receptor type 1 antagonism
      with losartan had no effect on plasma or lymphocytic angiotensin-converting
      enzyme.

PMID- 11588529
TI  - Pharmacologic inhomogeneity between the reactivity of intramural coronary
      arteries and arterioles.
AB  - We hypothesized that because of their size, anatomic location, and hemodynamic
      function, coronary arteries and arterioles would respond differently to
      vasoactive substances. Intramural arteries (281.7 +/- 23.1 microm) and arterioles
      (77.3 +/- 6.6 microm) of the left anterior descending coronary of rats were
      isolated and cannulated. Spontaneous tone was lower in arteries than in
      arterioles (81.1 +/- 5.7 vs. 53.0 +/- 3.9% of passive diameter, p < 0.05 at 60 mm
      Hg intraluminal pressure). Arterial tone was adjusted by the thromboxane receptor
      agonist U46619 (5 x 10(-8) M ) to reach an active tone close to that of
      arterioles. Bradykinin elicited dilations in both types of vessels. Acetylcholine
      (10(-6) - 10(-5) M ) dilated arteries (by 42.6 +/- 11.5 microm) but constricted
      arterioles (by 16.4 +/- 9.3 microm). Sodium nitroprusside and adenosine elicited
      significantly greater dilations in arterioles than in arteries (by 7.9 and 11.9%,
      respectively, p < 0.05), whereas dilations to norepinephrine were similar.
      Inhibition of nitric oxide synthesis caused a significantly smaller constriction
      in arteries (10.2 +/- 3.31%) than in arterioles (31.6 +/- 6.9%) and completely
      blocked bradykinin-and acetylcholine-induced dilations, whereas it did not affect
      dilations to sodium nitroprusside, adenosine, and norepinephrine. Compared with
      arteries, arterioles have a greater spontaneous tone and enhanced nitric oxide
      modulation of basal tone and exhibit greater responsiveness to nitric oxide and
      adenosine. In addition, nitric oxide synthase is activated differently by
      pharmacologic stimuli in these segments. The qualitative and quantitative
      differences among vasoactive responses of coronary arteries and arterioles
      demonstrated in this study suggest segment-specific roles for endothelial and
      metabolic factors in regulation of coronary vascular resistance.

PMID- 11588530
TI  - Protective effects of FK409, a novel nitric oxide donor, against postischemic
      myocardial dysfunction in guinea-pig hearts.
AB  - Effects of FK409 were investigated in perfused guinea-pig Langendorff hearts
      subjected to ischemia and reperfusion. Nitric oxide electrode, fluorometry, and
      31P nuclear magnetic resonance imaging were used to monitor changes in cellular
      high-phosphorous energy and nitric oxide and Ca2+ content in the heart together
      with simultaneous recordings of left ventricular developed pressure. After
      cardioplegic arrest with St. Thomas' Hospital solution, normothermic (37 degrees
      C) global ischemia was induced for 40 min, and hearts were reperfused for 40 min.
      FK409 at 10(-8) M, which has a minimum inotropic effect on nonischemic hearts,
      was added to the cardioplegic solution. Treatment with FK409 reduced left
      ventricular developed pressure during and after ischemia and improved
      postischemic recovery of left ventricular developed pressure from 55.4% at 40 min
      of reperfusion in FK409-free hearts up to 80.4% in hearts treated with FK409 (p <
      0.01). Flow rate at 1.5 min after treatment with the cardioplegic solution was
      27.7 ml/min in hearts treated with FK409 compared with 21.2 ml/min in drug-free
      hearts (p < 0.01). Treatment with FK409 significantly effected preservation of
      tissue level of beta-adenosine triphosphate at the end of ischemia or
      reperfusion. During ischemia, arrested with the cardioplegic solution,
      intracellular Ca2+ accumulation and nitric oxide release were reduced. At the end
      of ischemia in FK409-treated hearts, nitric oxide release was 86% greater than in
      drug-free hearts without reference to the Ca2+ concentration. In cardiac surgery,
      normothermic arrested hearts are subject to damage by oxygen free radicals in
      reperfusion injury. Therefore, nitric oxide exogenously supplied by FK409 was
      responsible for the cardioprotective action, presumably by acting directly as an
      oxygen radical scavenger during reperfusion. A specific nitric oxide donor, like
      FK409, may have therapeutic use as a nitric oxide-mediated vasorelaxant and
      additional protective action for reperfusion-injury hearts.

PMID- 11588531
TI  - Enrasentan improves survival, limits left ventricular remodeling, and preserves
      myocardial performance in hypertensive cardiac hypertrophy and dysfunction.
AB  - Evidence suggests that endothelin receptor antagonists may have therapeutic
      potential for the chronic treatment of heart failure. In the current study, the
      effects of an orally active mixed endothelin-A/endothelin-B (ETA /ETB ) receptor
      antagonist (enrasentan) were assessed in a model of cardiac hypertrophy and
      dysfunction (spontaneously hypertensive stroke prone rats) maintained on a high
      salt/high-fat diet. Echocardiography was used to quantify cardiac performance and
      left ventricular dimensions. Enrasentan (1,200 and 2,400 parts per million in the
      high-salt/high-fat diet) had no significant effects on body weight and systolic
      blood pressure. However, increases in heart rate were not observed in the
      enrasentan-treated groups at 12 weeks (p < 0.05). Enrasentan-treated groups
      exhibited significantly improved survival (90-95% vs. 30% [control rats] at 18
      weeks; p < 0.001). Enrasentan treatments also increased stroke volume (at 8, 12,
      and 16 weeks) and cardiac index (at 8 and 16 weeks) 33-50% and 45-63%,
      respectively. Enrasentan treatments reduced the relative wall thickness (14-27%
      at 8 and 12 weeks), ratio of left ventricular mass to body weight (20% at 12
      weeks), and ratio of terminal heart weight to body weight (16-23%, p < 0.05).
      Finally, circulating aldosterone concentration (54-57%) and proANF fragment (33%)
      were reduced in enrasentan-treated groups (54-57% and 33%, respectively). Mixed
      ETA /ETB receptor antagonism improves cardiac performance and attenuates
      ventricular remodeling and premature mortality in an aggressive hypertension
      model.

PMID- 11588532
TI  - Effects of adenosine receptor subtype A1 on ventricular and renal function.
AB  - The adenosine subtype 1 (A1) receptor, which may influence cardiac function and
      modulate renal function, may have particular relevance in congestive heart
      failure (CHF). However, the effects of A1 receptor inhibition in the setting of
      CHF are poorly defined. Systemic hemodynamics and indices of renal function were
      measured in pigs with pacing-induced CHF at 240 bpm for 3 weeks (n = 10) before
      and after A1 receptor blockade with 100 microg of BG9719 (1,3-dipropyl-8-[2-(5,6
      epoxynorbornyl)]xanthene) or in CHF pigs after infusion of vehicle only (n = 10).
      Heart rate, mean aortic pressure, and left ventricular peak pressure increased
      following A1 blockade in the CHF group, consistent with an adenosine inhibitory
      effect. However, cardiac output and global measures of vascular resistance did
      not significantly change following A1 blockade. Urine output increased twofold
      and sodium clearance increased threefold following A1 blockade (p < 0.05).
      Creatinine clearance increased following A1 blockade (127 +/- 17 vs. 62 +/- 7
      ml/min, p < 0.05). Selective A1 receptor blockade improved glomerular filtration
      rate and induced a natriuresis and diuresis in a model of CHF without adverse
      effects on cardiac function. These unique results suggest that renal A1 receptor
      activation may contribute to the reduced renal function associated with CHF.

PMID- 11588533
TI  - PC12 cells stimulate vascular smooth muscle growth.
AB  - Sympathetic nerves stimulate vascular growth. The mechanisms underlying this
      stimulation have not been fully elucidated. PC12 cells and cultures of vascular
      smooth muscle were used to study sympathetic stimulation of vascular smooth
      muscle growth. Media conditioned by undifferentiated and differentiated PC12
      cells stimulated the growth of vascular smooth muscle (446 +/- 47%).
      Differentiated PC12 cells produced more growth-stimulatory activity (61.5 +/- 9.6
      per 10(6) cells) than undifferentiated PC12 cells (28.5 +/- 8.8 per 10(6) cells).
      PC12 stimulation of vascular smooth muscle growth was not inhibited by adrenergic
      receptor antagonists but was reduced by an endothelin antagonist, suramin, and an
      antibody that neutralized the activity of platelet-derived growth factor. These
      data suggest that endothelin and platelet-derived growth factor, but not
      catecholamines, play a role in sympathetic stimulation of vascular smooth muscle
      growth.

PMID- 11588534
TI  - Eptifibatide and abciximab exhibit equivalent antiplatelet efficacy in an
      experimental model of stenting in both healthy volunteers and patients with
      coronary artery disease.
AB  - Platelet deposition and aggregation are the major determinants of acute
      thrombosis in coronary stents. We aimed to compare the antiplatelet efficacy of
      different treatments--glycoprotein (Gp) IIb/IIIa inhibitors and conventional
      antiaggregants--in an experimental model for stenting. Blood samples were
      obtained from patients with coronary artery disease (n = 15) and healthy
      volunteers (n = 8) and incubated either with eptifibatide (2.0 microg/ml),
      abciximab (3.0 microg/ml), indomethacin (15 microg/ml), or saline. Platelet
      adenosine diphosphate-induced aggregation in whole blood was assessed for all
      groups. Blood was also tested in an experimental circulation model containing
      metallic probes, on which platelet deposition in shear flow conditions was
      assessed by means of fluorescent-labeled platelet-specific (anti-GpIIIa and Ib)
      antibodies. Eptifibatide and abciximab, in comparison with indomethacin and no
      treatment, significantly reduced platelet aggregation (0, 0, 4, and 3 arbitrary
      units [AU], respectively; p < 0.001), anti-GpIIIa (2.25, 1.83, 11.24, and 13.42
      counts per second [cps]/mg, respectively; p < 0.001), and anti-GpIb binding
      (0.61, 0.61, 1.00, and 1.83 cps/mg, respectively; p < 0.001). Anti-GpIIIa and
      anti-GpIb binding were significantly correlated (R = 0.36; p < 0.01). Patients
      showed a higher anti-GpIIIa, but not anti-GpIb binding, than controls (8.43
      versus 3.33 cps/mg; p < 0.01), irrespective of treatment. In conclusion,
      eptifibatide and abciximab show equivalent in vitro antiplatelet efficacy,
      superior to that of indomethacin. Given the occurrence of GpIIb/IIIa platelet
      overexpression in the course of coronary artery disease, an extended use of
      GpIIb/IIIa inhibitors may be proposed to prevent acute thrombosis during routine
      coronary stenting.

PMID- 11588535
TI  - Efficacy, tolerability, and impact on quality of life of long-term treatment with
      manidipine or amlodipine in patients with essential hypertension.
AB  - This double-blind, multicenter trial compared antihypertensive efficacy,
      tolerability, and impact on quality of life of manidipine and amlodipine in
      patients with mild-to-moderate essential hypertension. Patients were randomly
      assigned to 48 weeks of once-daily manidipine, 10-20 mg, or amlodipine, 5-10 mg.
      Patients who did not respond to treatment after 12 weeks were also given
      enalapril, 10-20 mg, for the study's duration. The main efficacy end point was
      equivalence in sitting systolic (SiSBP) and diastolic (SiDBP) blood pressure
      reduction between the two drugs after 8 weeks (per protocol analysis). An
      intention-to-treat (ITT) analysis was performed in all patients with at least one
      efficacy determination during treatment. Quality of life was assessed by the
      "Subjective Symptoms Assessment Profile" (SSA-P) and "General Well-being
      Schedule" (GWBS), after 12 weeks of treatment. SiSBP reduction after 8 weeks was
      equivalent for manidipine (15.2 mm Hg, n = 227) and amlodipine (17.0 mm Hg, n =
      219). The corresponding figure for SiDBP was 11.3 mm Hg for manidipine and 12.3
      mm Hg for amlodipine. In the larger ITT population SiDBP was similarly and
      significantly reduced by manidipine (from 102 +/- 5 to 88 +/- 9 mm Hg, n = 241)
      and amlodipine (from 101 +/- 5 to 87 +/- 8 mm Hg, n = 240). Similar results were
      observed for SiSBP and standing SBP and DBP. Neither drug changed sitting or
      standing heart rate compared with baseline. SSA-P scores improved with manidipine
      but not amlodipine. GWBS total and partial scores increased more with manidipine
      than with amlodipine. Safety profile favored manidipine, which was associated
      with significantly less ankle edema than was amlodipine. This study shows for the
      first time that long-term treatment with the long-acting calcium channel blocker
      manidipine is as effective as treatment with amlodipine, has a better
      tolerability profile, and induces greater improvement in quality of life than
      amlodipine.

PMID- 11588536
TI  - Mortality associated with spontaneous bacterial peritonitis.

PMID- 11588537
TI  - Chronic heartburn: who can we safely NOT scope?

PMID- 11588538
TI  - Medical, surgical, and endoscopic treatment of gastroesophageal reflux disease
      and Barrett's esophagus.
AB  - Over the past decade, medical and surgical approaches to the patient with
      gastroesophageal reflux disease (GERD) have improved dramatically. Proton pump
      inhibitors have become the dominant medical therapy because of their high
      efficacy and safety. Laparoscopic surgical approaches have improved concomitantly
      with the advances in medical therapy, resulting in the perception that either
      continuous medical therapy or surgery are appropriate options for long-term
      maintenance of this chronic disorder. Recent approval of new endoscopic
      treatments for GERD has generated considerable interest, but acceptance of these
      techniques should be limited by the small number of patients studied to date, the
      lack of placebo controls, and the short duration of follow-up.

PMID- 11588539
TI  - Small intestinal neoplasms.
AB  - Small intestinal neoplasms are uncommonly encountered in clinical practice. They
      may occur sporadically, in association with genetic diseases (e.g., familial
      adenomatous polyposis coli or Peutz-Jeghers syndrome), or in association with
      chronic intestinal inflammatory disorders (e.g., Crohn's disease or celiac
      sprue). Benign small intestinal tumors (e.g., leiomyoma, lipoma, hamartoma, or
      desmoid tumor) usually are asymptomatic but may present with intussusception.
      Primary malignancies of the small intestine-including adenocarcinoma,
      leiomyosarcoma, carcinoid, and lymphoma-may present with intestinal obstruction,
      jaundice, bleeding, or pain. Extraintestinal neoplasms may involve the intestine
      via contiguous spread or peritoneal metastasis. Hematogenous metastases to the
      intestine from an extraintestinal primary are unusual and are most typical of
      melanoma. Because the small intestine is relatively inaccessible to routine
      endoscopy, diagnosis of small intestinal neoplasms is often delayed for months
      after onset of symptoms. When the diagnosis is suspected, enteroclysis is the
      most useful imaging study. Small bowel endoscopy (enteroscopy) is increasingly
      widely available and may permit earlier, nonoperative diagnosis.

PMID- 11588540
TI  - Anorectal and pelvic pain in women: diagnostic considerations and treatment.
AB  - Functional anorectal and pelvic pain disorders may cause considerable morbidity
      and frustration in many women. This article reviews current concepts of these
      often poorly understood disorders and provides suggestions for evaluating and
      managing women who may come to the attention of the practicing
      gastroenterologist.

PMID- 11588541
TI  - Side effects of corticosteroid therapy.
AB  - BACKGROUND: Corticosteroids have been used for the treatment of inflammatory
      bowel disease since the late 1940s. Upwards of 80% of patients may respond
      acutely to treatment with these medications, although 20% or more may be
      refractory and others become dependent on corticosteroid use to suppress disease
      activity. Side effects in the acute situation are relatively minor, although
      significant side effects (e.g., psychosis) have been encountered; the long-term
      use of corticosteroids is more problematic. This creates a milieu for the
      potential for serious and irreversible problems. These side effects are discussed
      in detail. The side effects from corticosteroids emulate from exogenous
      hypercortisolism, which is similar to the clinical syndrome of Cushing's disease.
      STUDY: PubMed search for years 1966-2000, author's personal manuscript/abstract
      files, and citations of known references. CONCLUSION: Short-term corticosteroid
      use is associated with generally mild side effects, including cutaneous effects,
      electrolyte abnormalities, hypertension, hyperglycemia, pancreatitis,
      hematologic, immunologic, and neuropsychologic effects, although occasionally,
      clinically significant side effects may occur. Long-term corticosteroid use may
      be associated with more serious sequel, including osteoporosis, aseptic joint
      necrosis, adrenal insufficiency, gastrointestinal, hepatic, and ophthalmologic
      effects, hyperlipidemia, growth suppression, and possible congenital
      malformations.

PMID- 11588542
TI  - Long-term prognosis of cirrhosis after spontaneous bacterial peritonitis treated
      with ceftriaxone.
AB  - Spontaneous bacterial peritonitis (SBP) is a frequent infection in cirrhotic
      patients with ascites, with a poor prognosis. The aims of this study were to
      determine the long-term survival of cirrhotic patients with SBP treated with
      ceftriaxone and to identify predictive factors related to survival. We studied 47
      first episodes of SBP treated with ceftriaxone with a mean follow-up of 272 days.
      Nineteen variables were recorded to evaluate their relation to survival. The most
      frequent organism that caused SBP was Escherichia coli (40%). Spontaneous
      bacterial peritonitis resolution was achieved in 67% of patients. After
      resolution, SBP recurrence was observed in 44% of patients. The cumulative
      probability of survival was 68.1% at 1 month and 30.8% at 6 months. After uni-and
      multivariate analyses of all cases, SBP resolution ( p = 0.0001) and
      international normalized ratio (INR) ( p = 0.0057) were found to be related to
      survival. Another analysis performed after SBP resolution and SBP recurrence
      showed that ascitic fluid-positive culture ( p = 0.0344) and INR ( p = 0.0218)
      had statistical significance as variables predictive of long-term survival. We
      conclude that the survival of cirrhotic patients is very short after the first
      episode of SBP, a fact probably related to advanced liver disease, as liver
      dysfunction (INR) is the most important factor related to long-term patient
      survival.

PMID- 11588543
TI  - Primary sclerosing cholangitis in patients with inflammatory bowel disease in
      Turkey.
AB  - BACKGROUND: Primary sclerosing cholangitis (PSC), which is a progressive
      cholestatic liver disease of unknown etiology, is strongly correlated with
      inflammatory bowel disease (IBD). GOALS: To determine the prevalence and describe
      the characteristics of PSC in patients with IBD in Turkey. STUDY: We determined
      the prevalence of PSC in patients with IBD admitted to our department during a 6
      year period. Also, patients with PSC were investigated from an IBD aspect.
      Regardless of whether the patient had symptoms such as itching, jaundice, and
      abdominal pain, endoscopic retrograde cholangiopancreatography was performed on
      those with elevated alkaline phosphatase, and liver biopsy was done if endoscopic
      retrograde cholangiopancreatography failed to bring about the diagnosis. RESULTS:
      Overall prevalence of PSC was 9 of 386 (2.3%) patients with ulcerative colitis
      (UC) and 4 of 110 (3.6%) patients with Crohn's disease (CD). Inflammatory bowel
      disease was established in 13 of 18 (72.2%; UC, 50.0%; CD, 22.2%) patients who
      were being observed for PSC. The male-to-female ratio was 5:4 in UC and 3:1 in CD
      patients with PSC. The mean age at diagnosis of PSC was 43.6 years (range, 30-54
      years) in patients with UC and 30.5 years (range, 26-41 years) in patients with
      CD. In patients with UC, the extension of colitis was total in seven patients
      (7/110, 6.3%) and left-sided in two patients (2/142, 1.4%). In patients with CD,
      the disease was located in the ileum and colon in one patient (1/47, 2.1%) and in
      colon alone in three patients (3/21, 14.2%). CONCLUSIONS: Prevalence of PSC
      associated IBD in the Turkish community appear to be similar to the results of
      western origin studies.

PMID- 11588544
TI  - Endoscopic ultrasonography in the evaluation of dilated common bile duct.
AB  - Abdominal ultrasonography (US) is the procedure of first choice in the evaluation
      of a dilated common bile duct (CBD). Dilated bile ducts and the level of
      obstruction can be reliably demonstrated with US, but the cause can be determined
      in only two thirds of patients. The aim of this prospective study was to assess
      the value of endoscopic ultrasonography (EUS) in detecting the cause of CBD
      dilatation in patients in whom US could not demonstrate the cause of dilation or
      in whom US revealed equivocal results. This 13-month study included the
      evaluation of 985 patients. Ninety consecutive patients found to have an enlarged
      CBD (diameter, > or =7 mm) of unexplained origin during US examination were
      included in this study. All patients were evaluated by EUS. Final diagnosis was
      determined by endoscopic retrograde cholangiopancreatography with or without
      sphincterotomy ( n = 72) and surgical exploration ( n = 17). The following
      diagnoses were made by EUS: choledocholithiasis in 40 patients, benign distal
      stricture in 8, choledochal cyst in 2, and ova of Ascaris in 1. The dilatation of
      CBD was found by EUS examination to be caused by a tumor in 13 cases. These
      included tumor of the papilla of the Vater in six patients, distal
      cholangiocarcinoma in five, and pancreatic head cancer in two. Endoscopic
      ultrasonography provided an accurate explanation for CBD dilatation in 70 of the
      76 patients (92%). We conclude that the diagnostic strategy for cholestasis
      should include US as a first choice. When the diagnosis of biliary obstruction
      remains probable, EUS should be carried out. Endoscopic retrograde
      cholangiopancreatography with sphincterotomy should be reserved for therapeutic
      use rather than diagnostic.

PMID- 11588545
TI  - Clinical and demographic predictors of Barrett's esophagus among patients with
      gastroesophageal reflux disease: a multivariable analysis in veterans.
AB  - BACKGROUND: The subgroup of patients with gastroesophageal reflux disease (GERD)
      that should undergo endoscopy to rule out Barrett's esophagus (BE) has not been
      well defined. GOALS: To examine demographic and clinical variables predictive of
      BE before endoscopy. STUDY: A validated GERD questionnaire was administered to
      107 patients with biopsy-proven BE and to 104 patients with GERD but no BE shown
      by endoscopy. Frequent symptoms were defined as symptoms that occurred at least
      once or more each week. Severity of symptoms was rated on a scale from 1 to 4
      (mild to very severe). Univariate analysis and multivariable logistic regression
      were performed to determine whether demographic characteristics and the duration,
      severity, and frequency of GERD symptoms were associated with the identification
      of BE. RESULTS: Eighty-five percent of the GERD patients and 82% of the BE
      patients completed the questionnaire. There was no difference between the groups
      in terms of race, gender, or proton pump inhibitor use. The BE patients were
      older (median age, 64 vs. 57 years, p = 0.04). In multivariable logistic
      regression, an age of more than 40 years ( p = 0.008), the presence of heartburn
      or acid regurgitation ( p = 0.03), and heartburn more than once a week ( p =
      0.007) were all independent predictors of the presence of BE. Interestingly,
      patients with BE were less likely to report severe GERD symptoms ( p = 0.0008)
      and nocturnal symptoms ( p = 0.03). Duration of symptoms, race, alcohol, and
      smoking history were not associated with BE. CONCLUSIONS: Upper endoscopy should
      be performed in GERD patients more than 40 years of age who report heartburn once
      or more per week. The severity of symptoms and the presence of nocturnal symptoms
      are not reliable indicators of the presence of BE.

PMID- 11588546
TI  - Gastrointestinal "crosses": an indication for surgery.
AB  - BACKGROUND: We present our experience with a unique type of foreign body that was
      specifically designed to arrest in its passage and cause perforation of the
      gastrointestinal tract. STUDY: Between 1994 and 1999, nine male prisoners from
      the same jail presented after ingestion of "crosses." A cross is constructed from
      the two halves of a standard paperclip that are tied together with a rubber band.
      The resulting construction is elastic: the two branches can be pulled to lie
      parallel, but they assume their original position once released. The cross is
      wrapped into paper with its branches parallel and ingested. After release from
      the wrapper, it "opens" and causes bowel perforations. RESULTS: All patients
      underwent emergency surgery for foreign body removal and treatment of
      peritonitis. A total of 19 crosses were removed from the patients. Six (32%) were
      found in the stomach; five, in the duodenum (28%); three, in the jejunum and
      ileum (16%); and one, in the pylorus and colon. There was no morbidity or
      mortality. CONCLUSIONS: Foreign bodies of this type never pass distally. The
      ultimate key to success in the management of patients who have ingested crosses
      is emergency surgical intervention.

PMID- 11588547
TI  - Colonoscopic hydrostatic balloon dilatation of Crohn's strictures.
AB  - Recurrent strictures cause considerable morbidity among many patients with
      Crohn's disease. We present a retrospective review of the outcome of patients who
      underwent endoscopic hydrostatic balloon dilatation of Crohn's strictures in our
      hospital over the past 7 years. All patients were under observation at
      Addenbrooke's Hospital, Cambridge. An initial assessment of all strictures was
      made radiologically, and any patient with active disease was treated before
      consideration of endoscopic dilatation. Dilatation was carried out with
      Microvasive Rigiflex balloons. Outcome after dilatation was assessed by review at
      subsequent clinic visits. Sixteen of 22 patients had resolution of their
      obstructive symptoms after dilatation, although one third of patients required
      more than two dilatations over the follow-up period. Six of 22 patients had
      persisting symptoms after endoscopic treatment, requiring surgery. There were no
      complications noted after any of the 71 dilatations that were performed. We
      conclude that hydrostatic balloon dilatation is a safe and effective alternative
      to surgery in the management of Crohn's strictures within the reach of the
      colonoscope.

PMID- 11588548
TI  - Do steroids help jaundice caused by primary sclerosing cholangitis?
AB  - The management of jaundice in patients with primary sclerosing cholangitis (PSC)
      is clinically challenging. In patients in whom the recognized precipitants for
      jaundice have been excluded, the outlook is uncertain at best. Some improve
      spontaneously, but the only treatment demonstrated to be effective is liver
      transplantation--which may not always be appropriate. We report three cases of
      jaundice in patients with PSC in whom corticosteroid therapy appeared to be
      beneficial.

PMID- 11588549
TI  - Nodular regenerative hyperplasia of the liver in a patient with celiac disease.
AB  - We present the case of dual adult celiac disease and liver disease with portal
      hypertension (esophageal varices); a percutaneous liver biopsy was compatible
      with nonspecific reactive hepatitis. Clinically, celiac disease was characterised
      by poor response to a gluten-free diet, with the development of a biochemical
      cholestasis and marked malnutrition. Our patient died of cerebral hemorrhage, at
      the age of 50 years, without associated risk factors. The necropsy demonstrated
      the existence of a nodular regenerative hyperplasia of the liver, splenic
      atrophy, gelatinous transformation of the bone marrow, and lymphocytic colitis.
      We discuss the different types of liver disorders associated with celiac disease
      and the possible relation between nodular regenerative hyperplasia and celiac
      disease, based on immunologic mechanisms.

PMID- 11588550
TI  - Follow-up of a patient with chronic hepatitis C-associated cryoglobulinemia
      during four and a half years of maintenance interferon treatment.
AB  - In this report, we present a patient with chronic hepatitis C-associated
      cryoglobulinemia who was kept on maintenance interferon treatment because of
      flare-ups in cryoglobulinemia-associated signs and hepatitis after withdrawal,
      dose reduction, and increase in dose intervals of interferon. This type of
      interferon use for treatment of cryoglobulinemia gave us a chance to observe the
      long-term effects of interferon on cryoglobulinemia and chronic hepatitis C
      remission for biochemical, virologic, and histologic aspects.

PMID- 11588551
TI  - Esophageal dysmotility in an adult with chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a group of hereditary disorders of
      impaired intracellular destruction of phagocytosed bacteria. Gastrointestinal
      manifestations are present, with hepatic abscess being the most common. In this
      case report, we present an adult with CGD with esophageal involvement, which has
      been described in only one other adult. The clinical history, modalities of
      diagnosis (including endoscopy, barium radiography, and esophageal manometry),
      and therapeutic strategies pertaining to the esophageal manifestations of CGD are
      discussed. A review of the pertinent available literature is provided.

PMID- 11588552
TI  - A solid cystic tumor of the pancreas with ossification and possible malignancy,
      coexisting nonfusion of the pancreatic ducts.
AB  - We report the case of a 34-year-old woman with a solid cystic tumor (SCT) of the
      pancreas accompanied by ossification and possible malignancy, coexisting
      nonfusion of the pancreatic ducts. There was a 24 x 29 x 33-mm mass with a
      prominent calcified lesion in the tail of the pancreas detected by abdominal
      ultrasonography, computed tomography, and magnetic resonance imaging. There were
      no distal metastases detected. Endoscopic retrograde pancreatography revealed
      nonfusion of the pancreatic ducts. The resected tumor consisted of solid and
      cystic components. The tumor was not encapsulated and included a severely
      ossified lesion inside. On microscopy, the tumor cells were small, eosinophilic,
      and proliferated in a solid or pseudo-papillary pattern. The tumor cells
      infiltrated into the surrounding normal pancreas parenchyma and invaded part of
      the mesentery. The immunostaining was positive for alpha-1-antitrypsin, neuron
      specific enolase, vimentin, and chromogranin A. In the literature, only a few
      cases of SCT of the pancreas described ossification. As far as we know, only
      three cases of SCT of the pancreas, which demonstrated nonfusion of the
      pancreatic ducts, have been reported. Thus, SCT of the pancreas with
      ossification, possible malignancy, and coexisting nonfusion of the pancreatic
      ducts is extremely rare.

PMID- 11588553
TI  - Hyperbaric oxygen therapy for severe ulcerative colitis.
AB  - Hyperbaric oxygen therapy has been used to successfully treat perineal Crohn's
      disease. We describe the first successful use of hyperbaric oxygen therapy in the
      treatment of ulcerative colitis, refractory to conventional therapies. Therapy
      consisted of 30 courses of 100% oxygen at a pressure of 2.0 atm absolute.
      Clinical remission was achieved on the basis of the Truelove-Witts and disease
      activity index scores. Corticosteroids were successfully tapered off once
      remission was achieved.

PMID- 11588554
TI  - Primary protein-losing enteropathy in anti-double-stranded DNA disease: the
      initial and sole clinical manifestation of occult systemic lupus erythematosus?
AB  - Hypoalbuminemia and generalized edema is a common clinical problem and the
      etiology is usually clear: cirrhosis, nephrotic syndrome, primary
      gastrointestinal disorders, malnutrition, etc. We present a 23-year-old
      previously healthy woman of Korean background who presented with generalized
      edema and a serum albumin of 9 g/L (normal, 35-45 g/L). Intensive investigations
      failed to reveal liver, renal, or inflammatory gastrointestinal mucosal disease.
      The antinuclear antibody was positive at a titer of 1:80, and extractable nuclear
      antigens were positive for SSA/anti-Ro. Anti-double-stranded DNA was markedly
      elevated at 4.6 kU/L (normal, 0-2.0 kU/L). A technetium 99M-labeled albumin study
      revealed a protein-losing enteropathy, despite normal histologic full-thickness
      jejunal biopsies. A diagnosis of occult systemic lupus erythematosus resulting in
      increased intestinal vascular permeability was made. The hypoalbuminemia remained
      in long-term remission after the initiation of induction and maintenance
      immunosuppression.

PMID- 11588555
TI  - Hepatic granulomas in chronic hepatitis C.

PMID- 11588556
TI  - Does anion gap predict severity in acute pancreatitis?

PMID- 11588557
TI  - Covered gastric perforation by the BioEnterics Intragastric Balloon.

PMID- 11588558
TI  - Sarcoidosis and inflammatory bowel disease.

PMID- 11588559
TI  - Correct visualization of the anal ring.

PMID- 11588577
TI  - Language representation in a patient with a dominant right hemisphere: fMRI
      evidence for an intrahemispheric reorganisation.
AB  - Studies have suggested that congenital left hemispheric (LH) frontal
      arteriovenous malformations (AVMs) are associated with an early transfer of
      language to right hemisphere (RH) frontal regions. The question remains whether
      such anatomofunctional reorganisation is due to RH compensatory abilities or to a
      general principle of lateral shift. In this study, we used fMRI language
      paradigms to investigate the case of a patient presenting aphasic symptoms
      following an haemorrhage due to a right frontal AVM. Prior to surgery, fMRI
      showed that language processing was confined to the RH, suggesting that language
      had not shifted during childhood from this congenitally dominant RH to the LH.
      After surgery, the patient presented severe aphasia that recovered to presurgical
      level within 70 days. At this time, fMRI showed that language tasks were still
      not associated with activations in the LH. These results suggest that the
      principles of early cerebral reorganisation after congenital lesions may differ
      in the RH and the LH. In addition, they support the idea that efficient
      restoration of language is achieved if a sufficiently large neuronal network is
      preserved around the lesion.

PMID- 11588578
TI  - A transient dominance of theta ERP component characterizes passive auditory
      processing: evidence from a developmental study.
AB  - This study analyzed relationships among co-existent EEG frequency responses
      during passive auditory stimulus processing. By applying quantifiers based on
      wavelet entropy, it is demonstrated that a short-lasting ordering of the complex
      post-stimulus EEG signal occurs as a result of a transient synchronization in the
      theta frequency channel. Further, by using a developmental model it is shown
      that, independently of the frequency content of the background EEG and ERPs, a
      highly-ordered microstate in the ERP is always determined by theta frequency.
      Thus, transient dominance of synchronized theta oscillations may reflect an
      important functional mechanism subserving stimulus information processing.

PMID- 11588579
TI  - Estrogen regulates bcl-x expression in rat hippocampus.
AB  - In this study, we examined whether experimental alterations of circulating
      estrogen levels are associated with changes in the expression of bcl-x, an
      inhibitor of apoptosis. We report that bcl-x mRNA expression in rat hippocampus
      significantly decreases after reduction of estrogen levels resulting from
      ovariectomy. Exposure of ovariectomized rats to 17beta-estradiol for either 5 or
      28 days restored bcl-x mRNA expression to levels at or above those observed in
      sham-ovariectomized control animals. These data demonstrate that physiological
      levels of estrogen regulate hippocampal expression of bcl-x, an important
      modulator of neuronal apoptosis. Estrogen-mediated regulation of bcl-x may be
      relevant to the maintenance of neuronal viability and may contribute to the
      mechanism of estrogen neuroprotection.

PMID- 11588580
TI  - Impaired P600 in neuroleptic naive patients with first-episode schizophrenia.
AB  - Deficits of working memory (WM) are recognized as an important pathological
      feature in schizophrenia. Since the P600 component of event related potentials
      has been hypothesized that represents aspects of second-pass parsing processes of
      information processing, and is related to WM, the present study focuses on P600
      elicited during a WM test in drug-naive first-episode schizophrenics (FES)
      compared to healthy controls. We examined 16 drug-naive first-episode
      schizophrenic patients and 23 healthy controls matched for age and sex. Compared
      with controls schizophrenic patients showed reduced P600 amplitude on left
      temporoparietal region and increased P600 amplitude on left occipital region.
      With regard to the latency, the patients exhibited significantly prolongation on
      right temporoparietal region. The obtained pattern of differences classified
      correctly 89.20% of patients. Memory performance of patients was also
      significantly impaired relative to controls. Our results suggest that second-pass
      parsing process of information processing, as indexed by P600, elicited during a
      WM test, is impaired in FES. Moreover, these findings lend support to the view
      that the auditory WM in schizophrenia involves or affects a circuitry including
      temporoparietal and occipital brain areas.

PMID- 11588581
TI  - Attentive and preattentive processing in narcolepsy as revealed by event-related
      potentials (ERPs).
AB  - Narcolepsy is a neurological disorder, characterised by excessive daytime
      sleepiness, sleep attacks, cataplexy and abnormal manifestations of rapid eye
      movement sleep. Recent studies suggest that neuropsychological impairments in
      narcolepsy may include memory and attention deficits due to a monoaminergic or
      cholinergic transmitter dysfunction. To explore the nature of cognitive problems,
      the P300 and mismatch negativity (MMN) event-related potentials were investigated
      in narcoleptic patients and matched controls. Narcoleptics showed significantly
      increased P300 amplitudes relative to controls, especially at frontal recording
      sites. While control subjects exhibited typically larger MMN over the right than
      the left hemisphere, in particular at frontal and central electrodes,
      narcoleptics did not show this asymmetry. These results are interpreted as
      possible alterations in cognitive preattentive and attentive processing
      associated with altered functioning of the prefrontal cortex in narcolepsy.

PMID- 11588582
TI  - Cerebral activation during a simple force production task: changes in the time
      course of the haemodynamic response.
AB  - An event-related paradigm was used to investigate the fMRI signal from the
      primary motor cortex (M1) and the supplementary motor area (SMA) during isolated
      isometric wrist extension at five different force levels. There was only a weak
      trend towards increased area of activation with increased force output, but there
      was a force-related increase in percentage change of signal within voxels in M1
      (Kendall Tc = 0.48, p < 0.01), which may indicate control of force output by
      variation of neural firing rate. In SMA there was a correlation between peak
      force output and time-to-peak of the haemodynamic response in SMA (Kendall Tc =
      0.74, p < 0.0001). This unexpected finding of a task-related change in the shape
      of the haemodynamic response within a single brain area requires further
      investigation. It may indicate a slower rise time at lower perfusion rates, or
      may be the result of inhibitory processes in motor control.

PMID- 11588583
TI  - Signals from skin mechanoreceptors used in control of a hand grasp
      neuroprosthesis.
AB  - We used signals from tactile mechanoreceptors in the skin of the index finger,
      recorded with an implanted cuff electrode, to automatically control grasp force
      in a hand grasp neuroprosthesis. Phasic events in the recorded nerve signal,
      related to mechanical events on the skin, were used to adjust electrical
      stimulation of hand muscles without any prior knowledge about muscle strength and
      properties of a held object. A simulated eating task was used to evaluate the
      hand grasp neuroprosthesis. When using the neuroprosthesis with feedback from
      natural sensors, the average grasp force could be reduced in comparison to not
      using feedback. Reducing grasp force is considered a major factor to decrease
      muscle fatigue, allowing a prolonged use of the hand grasp neuroprosthesis.

PMID- 11588584
TI  - Passive and active lower-limb movements delay upper-limb balance reactions.
AB  - This study investigated the influence of rhythmic lower-limb activity on the
      timing of upper-limb balance reactions. Compensatory grasping reactions were
      evoked in healthy subjects by rapid sagittal tilts of a chair under three
      conditions: (1) active leg pedaling, (2) passive (motor-driven) leg pedaling, and
      (3) no lower-limb movement (control task). Compared with control trials, both
      active and passive pedaling resulted in similar delays in the initiation (43-47
      ms) and execution (12-17 ms) of grasping reactions. The similarity between
      effects due to active and passive movement suggests that the conditioning arose
      predominantly from sensory discharge associated with lower-limb movement. These
      results may have important implications for understanding the influence of
      locomotion or other ongoing movement on the control of stability.

PMID- 11588585
TI  - Activation of striate cortex in the absence of visual stimulation: an fMRI study
      of synesthesia.
AB  - It has been suggested that internally generated visual perception involves the
      primary visual cortex V1. To test this hypothesis, a functional MRI study was
      conducted with a female subject with orthographic color-word synesthesia. This
      subject was selected as she reported clear involuntary visualization of
      auditorily presented verbal material. Hearing a word resulted in seeing the word
      in a particular color. fMRI scans were acquired while the subject performed two
      verbal tasks (passive listening to words and verbal fluency). Significant
      activity was detected in primary visual cortex, in the absence of external visual
      stimulation. This finding provides evidence for a role of modulatory feedback
      connections between associative and primary visual areas in visual experience
      without direct visual stimulation.

PMID- 11588586
TI  - D1-receptor dependent synaptic potentiation in the basal ganglia of quail chicks.
AB  - Properties of local synapses were analyzed in lobus parolfactorius (LPO; avian
      homologue of caudate-nucleus) of quail chicks by using slice preparations in
      vitro. Field-potential extracellular and whole-cell intracellular recordings
      revealed excitatory synaptic inputs converging from dorsal and ventral regions
      within LPO. With exogenous dopamine (100 microM) in the perfusate, synchronized
      conditioning stimulation induced biased changes in the dorsal and the ventral
      inputs; potentiation in the dorsal input and depression in the ventral input in
      average. On the other hand, de-synchronized conditioning failed to induce such
      biased changes, although the differences were not statistically significant. SCH
      23390 (3 microM) blocked the dorsal potentiation, while AP-5 (100 microM) tended
      to block both of these changes. The plastic nature may underlie the memory
      formation in appetitive/aversive learning tasks.

PMID- 11588587
TI  - Co-association of parkin and alpha-synuclein.
AB  - Parkin and alpha-synuclein are two proteins that are associated with the
      pathophysiology of Parkinson's disease (PD). Parkin is present in Lewy bodies and
      axonal spheroids in brains affected by PD, and mutations in parkin cause
      hereditary forms of Parkinsonism. Alpha-synuclein is a major component of Lewy
      bodies and is associated with rare cases of PD. We now show that parkin binds to
      alpha-synuclein, including conditions associated with alpha-synuclein
      aggregation. Parkin and alpha-synuclein complexes were observed in BE-M17 cells
      under basal conditions, in BE- M17 cells under oxidative conditions and in brains
      from control or PD donors. Double staining of PD brains shows parkin and alpha
      synuclein co-localize to the same pathological structures (both Lewy bodies and
      axonal spheroids). These results suggest that parkin interacts with alpha
      synuclein and could contribute to the pathophysiology of PD more generally than
      was previously considered.

PMID- 11588589
TI  - Behavioural and functional anatomical correlates of deception in humans.
AB  - Brain activity in humans telling lies has yet to be elucidated. We developed an
      objective approach to its investigation, utilizing a computer-based interrogation
      and fMRI. Interrogatory questions probed recent episodic memory in 30 volunteers
      studied outside and 10 volunteers studied inside the MR scanner. In a counter
      balanced design subjects answered specified questions both truthfully and with
      lies. Lying was associated with longer response times (p < 0.001) and greater
      activity in bilateral ventrolateral prefrontal cortices (p < 0.05, corrected).
      These findings were replicated using an alternative protocol. Ventrolateral
      prefrontal cortex may be engaged in generating lies or withholding the truth.

PMID- 11588588
TI  - Expression of beta-synuclein in normal human astrocytes.
AB  - Although alpha- and beta-synucleins are expressed predominantly in presynaptic
      nerve terminals, recent studies have demonstrated that alpha-synuclein is also
      expressed in cultured astrocytes and oligodendrocytes. We determined whether beta
      synuclein might be expressed in astrocytes. Beta-synuclein mRNA and protein were
      detected in normal human astrocytes in culture, and immunofluorescent staining
      showed that beta-synuclein protein was expressed within the cytoplasm and
      nucleus. Furthermore, beta-synuclein immunoreactivity was present in astrocytes,
      but not in oligodendrocytes, in normal human brain tissues. Ultrastructurally,
      beta-synuclein immunoreactivity was found in the cytoplasm of astrocytes, in
      association with the plasma membrane, ribosomes, rough endoplasmic reticulum and
      the nuclear outer membrane. The novel expression of beta-synuclein in astrocytes
      may provide an important insight about the role of this protein.

PMID- 11588590
TI  - Effects of aging on event-related neural activity related to prospective memory.
AB  - The neural foundation of age-related declines in prospective memory was explored
      using event-related brain potentials (ERPs). Consistent with previous research, a
      decline in the efficiency of prospective memory was observed in older adults that
      reflected a decrease in veridical prospective responses and an increase in false
      prospective responses. The neurophysiological data revealed an age-related
      reduction in the amplitude of modulations of the ERPs related to prospective
      remembering, but not visual information processing, and are consistent with the
      hypothesis that a reduction in the efficiency of a frontally mediated neural
      system contributes to prospective memory failure in older adults.

PMID- 11588591
TI  - Stimulus-dependence of NO-mediated neuronal activation: a Fos expression study in
      the hippocampus and cortex of lactating rats.
AB  - We investigated how simultaneous manipulation of suckling and i.c.v. injection of
      nitric oxide (NO)-related pharmacological agents affect Fos activation in the
      hippocampus and cortex of lactating rats. Dams received drugs or vehicle
      injection just prior to reunion with their pups following a 12 h separation and
      Fos protein activation was examined after 2 h of suckling. In conscious dams,
      sodium nitroprusside (SNP, an NO donor) significantly activated Fos expression in
      the hippocampus and cortex compared with vehicle or an NO synthase inhibitor.
      Urethane anaesthesia abolished Fos expression in the cortex, but not in the
      hippocampus following simultaneous SNP injection and resumption of suckling. Fos
      activation in the hippocampus and cortex was significantly attenuated when SNP
      was injected alone (without dam-pups reunion after separation). Coincident
      injection of SNP with a NO synthase inhibitor abolished all Fos activation in the
      hippocampus and cortex. In chronically lactating rats (without any interruption
      of suckling) SNP injection failed to activate any Fos expression. These
      observations underscore the importance of stimulus modality in revealing the
      dynamics of NO-mediated neuronal function within a discrete tissue entity such as
      the hippocampus or the cortex, which may be relevant to other regions of the
      brain.

PMID- 11588592
TI  - Cloning and functional expression of ASIC-beta2, a splice variant of ASIC-beta.
AB  - We have isolated a cDNA encoding a splice variant of ASIC (acid-sensing ion
      channel)-beta from the rat trigeminal ganglion. This clone, designated ASIC
      beta2, showed a 342 base deletion just after the first transmembrane domain in
      ASIC-beta. RT-PCR experiments revealed that ASIC-beta2 was expressed exclusively
      in the trigeminal ganglion and dorsal root ganglion. In situ hybridization showed
      that ASIC-beta2 mRNA was concentrated in both small diameter and large diameter
      neurons and co-localized with ASIC-beta mRNA within single sensory neurons in the
      trigeminal ganglion. When expressed in Xenopus oocytes, ASIC-beta2 was inactive
      by itself. However, it associated with ASIC-beta to form heteromers, which
      display lower affinity for protons than ASIC-beta alone.

PMID- 11588593
TI  - BDNF and NT3 extend the critical period for developmental climbing fibre
      plasticity.
AB  - The effect on neonatal brain plasticity of two neurotrophins, brain derived
      neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), was studied using the rat
      olivocerebellar projection as a model. Unilateral transection of climbing fibres
      (CFs) in the rat before postnatal day 7 induces reinnervation of the deafferented
      hemicerebellum, but this does not occur if the transection is performed after
      postnatal day 10. Eleven-day-old day rats underwent unilateral CF transection
      followed by neurotrophin injection into the denervated cerebellar cortex 24 h
      later. The exogenous neurotrophins induced CF reinnervation of the denervated
      hemicerebellum. However BDNF was more efficacious than NT-3. Thus two
      neurotrophins can extend the window of neonatal brain plasticity, therefore
      suggesting potential therapeutic use after brain trauma.

PMID- 11588594
TI  - Impaired detection of variable duration embedded tones in ectopic NZB/BINJ mice.
AB  - Utilizing rodent models, prior research has demonstrated a significant
      association between focal neocortical malformations (i.e. induced microgyria,
      molecular layer ectopias), which are histologically similar to those observed in
      human dyslexic brains, and rate-specific auditory processing deficits as seen in
      language impaired populations. In the current study, we found that ectopic
      NZB/BINJ mice exhibit significant impairments in detecting a variable duration
      5.6 kHz tone embedded in a 10.5 kHz continuous background, using both acoustic
      reflex modification and auditory event-related potentials (AERP). The current
      results add further support to the association between focal cortical
      malformations and impaired auditory processing, and the notion that these
      auditory effects may occur regardless of the cortical location of the anomaly.

PMID- 11588595
TI  - Maternal glucocorticoid hormone influences nerve growth factor expression in the
      developing rat brain.
AB  - Rat pups nursed from birth by mothers with increased plasma corticosterone show
      long-lasting biochemical and behavioral modifications. Here we have investigated
      nerve growth factor (NGF) concentrations in the basal forebrain, prefrontal
      cortex and hippocampus of both male and female offspring at 11 days of age.
      Maternal hypercorticosteronemia was achieved by giving corticosterone-enriched
      water (200 microg/ml) from delivery. There was a significant increase of NGF in
      the basal forebrain of both sexes and no changes in the prefrontal cortex. In the
      hippocampus, an increase in NGF was found in males. These results indicate that a
      moderate increase of corticosterone in the lactating mother modulates NGF in the
      developing rat. We propose that these effects contribute directly to the long
      lasting behavioral and biochemical modifications in pups nursed by
      hypercorticosteronemic mothers.

PMID- 11588596
TI  - Vesicular glutamate transporter transcript expression in the thalamus in
      schizophrenia.
AB  - Previously, we have reported alterations in thalamic NMDA receptor subunit and
      excitatory amino acid transporter expression in schizophrenia, consistent with
      the hypothesis that thalamic glutamatergic dysfunction may contribute to the
      pathophysiology of this illness. We have generalized this hypothesis to include
      other molecules of the glutamate synapse. Using riboprobes specific for human
      brain-specific Na+-dependent inorganic phosphate transporter (BNPi) and
      differentiation-associated Na+/Pi co-transporter (DNPi), both vesicular glutamate
      transporters, in situ hybridization was performed in the thalami of persons with
      schizophrenia and comparison subjects. We detected increased expression of DNPi
      mRNA in the thalamus in schizophrenia, while BNPi mRNA was not expressed in the
      thalamus in any subjects. These findings support the hypothesis of glutamatergic
      dysfunction in the thalamus in schizophrenia.

PMID- 11588598
TI  - Expression of hMTH1 in the hippocampi of control and Alzheimer's disease.
AB  - The oxidized purine nucleoside triphosphatase, hMTH1, has a critical role towards
      preventing errors caused by oxidized purine nucleoside triphosphates such as 8
      oxo-dGTP and 2-hydroxy-dATP. We investigated the immunohistochemical expression
      of hMTH1 in human hippocampal postmortem tissues representing non-neurological
      disease and Alzheimer's disease (AD). In the non-neurological subjects the hMTH1
      protein was enriched in the stratum lucidum at CA3 corresponding to mossy fiber
      synapses. In AD subjects, the synaptic immunoreactivities at CA3 were
      significantly decreased, whereas they tended to be increased at the entorhinal
      cortex. We suggest that the expression of hMTH1 indicates indirect evidence of
      oxidative stress and its regulation is regionally differentiated in AD.

PMID- 11588597
TI  - Voltage-sensitive dye versus intrinsic signal optical imaging: comparison of
      optically determined functional maps from rat barrel cortex.
AB  - Using intrinsic and voltage-sensitive dye optical imaging methods, somatosensory
      evoked neural activity and the consequent metabolic activity were visualized in
      the barrel cortex at high temporal and spatial resolution. We compared maps of
      neural and metabolic activity from the perspective of spatial distribution in the
      cortex. There was good agreement between the two functional maps, if the extent
      of metabolic activity before a prominent increase in cerebral blood volume (CBV)
      was assessed. This result indicates that oxygen consumption occurs before CBV
      changes, in approximately the same cortical area as that in which the preceding
      neural activity was evoked. This also suggests that the intrinsic signal reflects
      subthreshold synaptic activity, as well as spiking activity, which is similar to
      the dye-related signals.

PMID- 11588599
TI  - Adenosine and caffeine modulate circadian rhythms in the Syrian hamster.
AB  - Extracellular adenosine accumulates in some brain areas during sleep deprivation.
      In Syrian hamsters, both sleep deprivation and adenosine A1 agonists can inhibit
      phase shifts of circadian rhythms to light at night. Sleep deprivation in the day
      (sleep period) can shift circadian phase. We examined whether the A1 agonist N
      CHA mimics this effect. N-CHA (i.p. or i.c.) in the mid-sleep period induced dose
      dependent shifts similar to those induced by 3 h sleep deprivation. The adenosine
      antagonist caffeine administered systemically at the mid-sleep period induced
      arousal without shifts, and dose-dependently attenuated shifts to a 3 h sleep
      deprivation procedure (running in a novel wheel). Adenosine may participate in
      resetting of the circadian clock by manipulations of behavioral state.

PMID- 11588600
TI  - PSD95 protein level rises in murine somatosensory cortex after sensory training.
AB  - Proteins of the postsynaptic density are implicated in mechanisms of synaptic
      plasticity. We examined involvement of PSD95 and alphaCaMkII in learning
      dependent plastic changes of representational maps in somatosensory cortex of
      mice. The barrel cortex of mice was examined following a 3 day long classical
      conditioning training, in which activation of facial vibrissae was linked to an
      aversive stimulus. This procedure produced expansion of cortical representations
      of vibrissae involved in the training. In subcellular fraction enriched in
      postsynaptic densities from the barrel cortex, it was estimated by Western
      blotting that the level of PSD95 increased after the training by about 50%, while
      the level of CaMkII remained unchanged. The results indicate involvement of PSD95
      in learning-dependent cortical plasticity.

PMID- 11588601
TI  - Beta-scorpion toxin induces the release of gamma-[3 H]aminobutyric acid in rat
      brain slices.
AB  - The effect of the beta-scorpion toxin, TiTX gamma on the release of [3H]GABA from
      rat brain cortical slices is described. The stimulatory effect of TiTX gamma on
      the release of [3H]GABA was dependent on incubation time and TiTX gamma
      concentration with an EC50 of 0.19 microM. The scorpion toxin effect was calcium
      dependent and was completely inhibited by tetrodotoxin. beta-Alanine also induced
      the release of [3H]GABA and this effect was not inhibited by tetrodotoxin but was
      additive in the presence of TiTX gamma. The data suggest a neuronal origin for
      the release of [3H]GABA by TiTX gamma.

PMID- 11588602
TI  - The impact of transcranial magnetic stimulation on cognitive processing: an event
      related potential study.
AB  - Several neuropsychological studies have shown that repetitive transcranial
      magnetic stimulation (rTMS) can improve cognitive processing. We performed a
      study on the impact of rTMS on cognitive processing as measured by a
      neurophysiological method. In 14 healthy subjects, visually evoked event-related
      potentials (ERP) and mean choice reaction time were measured before and after 20
      Hz rTMS of the left and of the right prefrontal cortex. The data were compared to
      sham stimulation and to 1 Hz single TMS. P3 latencies and reaction time were
      significantly decreased by rTMS of the left but not of the right prefrontal
      cortex, single TMS did not have any significant impact on the ERP components. We
      conclude that the facilitating effects of rTMS on cognitive processing can be
      proven even by objective neurophysiological measures.

PMID- 11588603
TI  - Impaired delay but normal trace eyeblink conditioning in PLCbeta4 mutant mice.
AB  - To elucidate the functional role of phospholipase Cbeta4 (PLCbeta4), which is
      highly expressed in the Purkinje cells of the rostral cerebellum, cerebellar long
      term depression (LTD) and delay and trace eyeblink conditioning were investigated
      in PLCbeta4-deficient mice. Rostral cerebellar LTD and delay eyeblink
      conditioning were severely impaired, whereas trace eyeblink conditioning was not.
      These results indicate that PLCbeta4 is essential for LTD in the rostral
      cerebellum and delay conditioning, but not trace conditioning. Rostral cerebellar
      LTD may be required as a neural substrate for delay conditioning, but is not
      required for trace conditioning.

PMID- 11588604
TI  - ATP-induced movement of the stalks of isolated cochlear Deiters' cells.
AB  - Deiters' cells, a type of supporting cell in the sensory epithelium of the
      cochlea, the organ of Corti, have been found to have P2X and P2Y adenosine
      triphosphate (ATP) receptors on their surfaces. Activation of these receptors may
      alter the mechanical properties of Deiters' cells and thus of the organ itself.
      ATP was applied to Deiters' cells isolated from guinea pig cochlea and the tip of
      the cells' stalk monitored for an ATP induced movement. Application of 100 microM
      ATP to the cell body of isolated Deiters' cells induced a small, reversible
      movement of the cells' stalk whereas application of bathing media did not.
      Results suggest that in vivo endogenous extracellular ATP released from
      unidentified locations could alter cochlear mechanics.

PMID- 11588605
TI  - Convergence of Y and non-Y channels onto single neurons in the superior colliculi
      of the cat.
AB  - Receptive field properties of single neurons in the cat superior colliculus were
      examined following selective conduction-block of Y-type fibers in contralateral
      optic nerve. Although the responses evoked by photic stimuli presented via the Y
      blocked eye were significantly weaker than those evoked by stimuli presented via
      the normal eye, > 85% of collicular cells were binocular. Furthermore, when
      binocular cells were stimulated via the Y-blocked eye their median upper cut-off
      velocity (100 degrees /s) was significantly lower than that (400 degrees /s) for
      stimuli presented via the normal eye. Thus, there is a substantial degree of
      excitatory convergence of Y- and non-Y- information channels on single collicular
      neurons and the responses to high velocity of motion appear to depend on the
      integrity of Y-type input.

PMID- 11588606
TI  - 3-hydroxy-3-methylglutaryl-coenzyme A reductase mRNA in Alzheimer and control
      brain.
AB  - Statins are widely used pharmaceutical agents which lower plasma cholesterol by
      inhibiting the rate controlling enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A
      (HMG-CoA) reductase. One epidemiological study suggests that statin therapy may
      provide protection against Alzheimer disease (AD). The aim of the present study
      was to determine the relative expression of HMG-CoA reductase mRNAs in various
      areas of brain as well as in peripheral organs and to compare values in AD and
      control cases. High levels of the mRNA were found in all areas of brain but no
      obvious differences were found between AD and controls. We conclude that brain
      has a robust capacity to synthesize cholesterol which appears to be unaffected by
      AD pathology.

PMID- 11588607
TI  - Changes of contrast gain in cat dorsal lateral geniculate nucleus by dopamine
      receptor agonists.
AB  - The modulatory effects of dopamine (DA) on the contrast gain of retino-geniculate
      transmission were tested with local micro-iontophoretical application of DA and
      the DA receptor agonists SKF38393 (SKF, D1/D5) and quinpirole (QUIN, D2/D3/D4)
      while recording visually induced spike activity of relay cells of the dorsal
      aspect of cat lateral geniculate nucleus (dLGN) in the anesthetised and paralyzed
      preparation. DA and QUIN could either facilitate or inhibit visual activity in a
      dose-dependent fashion: small amounts caused a facilitation while larger
      quantities resulted in a more (DA) or less (QUIN) strong inhibition. The effect
      of SKF was almost always suppressive and increased with the amount of drug
      applied. The absolute change in activity was depending on stimulus contrast and
      the strength of the elicited response: facilitation and inhibition of activity
      was proportional to stimulus contrast and response strength and thus resulted in
      a changed contrast gain. The results indicate that the visual deficits found in
      Parkinson's disease patients my be not solely related to retinal dysfunctions.

PMID- 11588608
TI  - The AMPA receptor allosteric potentiator PEPA ameliorates post-ischemic memory
      impairment.
AB  - PEPA (4-[2-(Phenylsulphonylamino)ethylthio]-2,6-difluorophenoxyacetamide) is a
      recently developed allosteric potentiator of AMPA receptors that preferentially
      affects flop splice variants. We tested the effects of PEPA on ischemia-induced
      memory deficit in rats. Permanent unilateral occlusion of the middle cerebral
      artery induced severe impairment of performance of rats in the Morris water maze
      test. Repeated intravenous administration of PEPA (1, 3, 10 mg/kg/day for 10
      days) improved test performance. In contrast, a corresponding dose of aniracetam,
      a representative potentiator of AMPA receptor, did not significantly improve test
      performance. Thus, PEPA is more effective than aniracetam in reversing impaired
      memory function as assessed by the Morris water maze test; and PEPA may be an
      effective compound for the treatment of impaired memory.

PMID- 11588609
TI  - Lens epithelium-derived growth factor (LEDGF) delays photoreceptor degeneration
      in explants of rd/rd mouse retina.
AB  - Lens epithelium derived growth factor (LEDGF) has been shown to rescue embryonic
      chick photoreceptor cells from serum starvation and heat stress, light damaged
      photoreceptor cells in Lewis rats, and photoreceptor cells in RCS rats. The aim
      of our study is to study the rescue effect of LEDGF on photoreceptor cells in the
      rd/rd mouse using our long-term serum free organ culture. At the end of this
      culture period of 21-26 days LEDGF treated rd mouse retina showed an increased
      photoreceptor survival compared to the untreated controls. LEDGF has no effect on
      expression and localization of opsin and arrestin in the rod photoreceptor cells
      when RPE is present. The protective potency of LEDGF on the retinal photoreceptor
      cells is similar to that of BDNF. LEDGF is known to activate heat shock proteins
      (Hsps) and the elevated Hsps are also reported to suppress apoptosis.

PMID- 11588610
TI  - Physiology of morphologically identified cells of the bullfrog fungiform papilla.
AB  - Voltage-gated ionic current and the response to quinine were studied on the four
      types of morphologically identified taste cells of the bullfrog fungiform papilla
      by whole-cell patch clamp recording with a Lucifer yellow-filled pipette. Dye
      coupled type Ia cells (mucous cells) did not show voltage-activated currents.
      Type Ib cells (wing cells) characterized by the fin-like processes, type II cells
      (rod cells) having a thick straight dendrite running to the surface and type III
      cells with a thin dendrite had voltage-gated sodium (INa) and potassium currents
      (IK) and generated action potentials. The amplitude of INa was significantly
      larger in type Ib and II cells than in type III cells. Type Ib and II cells
      responded to quinine but Type III cells did not.

PMID- 11588611
TI  - Pain relief induced by repetitive transcranial magnetic stimulation of precentral
      cortex.
AB  - Chronic electrical stimulation of the precentral (motor) cortex using surgically
      implanted electrodes is performed to treat medication-resistant neurogenic pain.
      The goal of this placebo-controlled study was to obtain such antalgic effects by
      means of a non-invasive cortical stimulation using repetitive transcranial
      magnetic stimulation (rTMS). Eighteen patients with intractable neurogenic pain
      of various origins were included and underwent a 20 min session of either 10 Hz,
      0.5 Hz or* sham rTMS over the motor cortex in a random order. A significant
      decrease in the mean pain level of the series was obtained only after 10 Hz rTMS.
      This study shows that a transient pain relief can be induced by 10 Hz rTMS of the
      motor cortex in some patients suffering from chronic neurogenic pain.

PMID- 11588612
TI  - Plasmin cleaves Abeta42 in vitro and prevents its aggregation into beta-pleated
      sheet structures.
AB  - The formation, aggregation and deposition of amyloid beta peptide (Abeta) is
      implicated in the aetiology of Alzheimer's disease. Impairment of proteolytic
      degradation of Abeta may be a key factor in the progression of the disease. We
      have used RP-HPLC and thioflavin T fluorescence to demonstrate that Abeta42 is
      rapidly cleaved by the protease plasmin and that cleavage prevented the
      aggregation of Abeta42, and its cleavage products, into beta-pleated sheet
      structures. Plasmin may fulfil a similar role in vivo.

PMID- 11588613
TI  - Asymmetrical reductions of hippocampal NMDAR1 glutamate receptor mRNA in the
      psychoses.
AB  - The psychotomimetic properties of NMDA glutamate receptor antagonists suggest
      there may be disease related changes of this receptor in schizophrenia. Using in
      situ hybridisation histochemistry (ISHH), we measured mRNA for the obligatory
      NMDAR1 subunit of the NMDA glutamate receptor in post-mortem samples of
      hippocampus from schizophrenics, depressives, bipolar patients and normal
      controls. A significant main effect of diagnosis was observed in the dentate
      gyrus (ANOVA, p = 0.004) and a trend in the CA3 region (ANOVA, p = 0.06), with
      all psychiatric groups having reduced NMDAR1 mRNA levels compared to normal
      controls. In contrast to the affectively ill groups, the reductions in
      schizophrenics were more pronounced in the left side compared to the right.
      Expression of poly A mRNA also showed left-sided losses in the dentate gyrus in
      schizophrenia but reductions in NMDAR1 remained significant when expressed as a
      ratio of poly A. The findings confirm a recent report of reduced hippocampal
      NMDAR1 mRNA in schizophrenia. However, our new evidence suggests that this is a
      feature of both affective and schizophrenic disorders and that schizophrenia is
      distinguished from the others by left-sided reductions in hippocampal NMDAR1 gene
      expression.

PMID- 11588614
TI  - Effects of maternity on auditory event-related potentials to human sound.
AB  - Auditory event-related brain potentials (ERPs) were recorded in response to an
      emotional (a baby's cry) and a neutral (a word) stimulus in a group of mothers 2
      5 days after childbirth (n = 20) and in control women (n = 18) who were not in
      the state of early motherhood. For each mother, her own infant's cry was recorded
      and used as the cry stimulus, whereas a strange baby's cry was used for control
      women. The word stimulus was identical for both groups. Stimuli were presented in
      intermittent trains in order to study the arousal responses to the first stimuli
      of the trains, and refractoriness of ERPs during stimulus repetition. The N100
      responses were significantly larger in amplitude in mothers than in control
      women, not only to the emotional cry stimuli but also to the neutral word
      stimuli. The finding suggests a general increase in alertness and arousal in
      mothers, which may be necessary in enabling the mother to be continuously alert
      to her infant's needs. This allows good care of the infant and may be essential
      in building an emotional tie between the mother and her child.

PMID- 11588615
TI  - Morphine withdrawal increases expression of GABA(A) receptor epsilon subunit mRNA
      in locus coeruleus neurons.
AB  - An increase in the activity of brain stem locus coeruleus noradrenergic neurons
      has been hypothesised to be a major factor accounting for opiate withdrawal
      symptoms. These neurons are under GABAergic inhibition. Their GABA(A) receptors
      have unique pharmacological properties, most likely due to the enriched
      expression of GABA(A) receptor subtypes containing novel epsilon and straight
      theta subunits. Using in situ hybridisation of cryostat sections, we now report a
      significant increase in the epsilon subunit mRNA expression after precipitation
      of opioid withdrawal by naloxone. Similar changes were detected in tyrosine
      hydroxylase mRNA expression. The results suggest increased formation of unique
      GABA(A) receptor subtype(s) in the locus coeruleus neurons during increased
      neuronal activity.

PMID- 11588616
TI  - Estrogen affects the expression of Ca2+/calmodulin-dependent protein kinase IV in
      amygdala.
AB  - We examined the effects of long-term estradiol benzoate (E2) treatment on protein
      expression of Ca2+/calmodulin-dependent protein kinase IV (CaMK IV) in the
      amygdala of ovariectomized (OVX) rats. Western blot analysis revealed increased
      protein levels of CaMK IV in the nuclear but not in the membranal or cystolic
      fraction of total amygdala in E2-treated compared to OVX rats. Significant
      increases in levels of CaM kinase IV gold immunolabeling were seen in the medial
      and basomedial, but not in the central or basolateral, amygdala of E2 compared to
      OVX rats, indicating the neuroanatomical heterogeneity of the E2 effect. These
      results suggest that CaMK IV may act as a molecular target for actions of
      estrogen in the amygdala of rats.

PMID- 11588617
TI  - Supramodal effects of galvanic vestibular stimulation on the subjective vertical.
AB  - This study investigated whether the tilt of the subjective vertical induced by
      galvanic vestibular stimulation, demonstrated by asking subjects to set a rod to
      the vertical, was specific to the visual modality or could be found in two tasks
      relying on proprioceptive and somatosensory cues. In all cases, settings were
      significantly deviated in the direction of the anode, but errors were smaller in
      the somatosensory tasks than in the visual task. We propose that the effects
      observed in the somatosensory modality reflects only a modification of the
      central representation of gravity, whereas visual effects are also in part the
      consequence of unregistered ocular torsion.

PMID- 11588618
TI  - Co-expression of P2X receptor subunits on rat nodose neurons that bind the
      isolectin GS-I-B4.
AB  - Triple fluorescent histochemistry was used to describe the types of overlap in
      visceral sensory neurons (nodose ganglion) for the labeling of the isolectin B4
      from Griffonia simplicifolia type one (GS-I-B4) and their immunoreactivity (IR)
      for two of the ATP receptor subunits (P2X1/3 or P2X2/3). The vast majority of
      nodose neurons expressed GS-I-B4-binding and most of these displayed P2X receptor
      IR. Most of the P2X-IR was co-expressed on these individual nodose neurons
      (P2X1/P2X3 or P2X2/P2X3). A very small subpopulation of neurons that were GS-I-B4
      negative but P2X positive displayed a very high relative intensity of P2X3-IR.
      The functional role that these expression patterns play in visceral sensory
      processing is currently unclear.

PMID- 11588620
TI  - Matrix metalloproteinase 2 gene knockout has no effect on acute brain injury
      after focal ischemia.
AB  - Matrix metalloproteinases (MMPs) may contribute to tissue damage after cerebral
      ischemia. In this study, wildtype and MMP-2 knockout mice were subjected to
      permanent and transient (2 h) occlusions of the middle cerebral artery. Gelatin
      zymography showed that MMP-9 levels were increased in all brains after ischemia.
      MMP-2 levels did not show a significant increase in wildtype mice, and were not
      detectable in knockout mice. Laser doppler flowmetry demonstrated equivalent
      ischemic reductions in perfusion in wildtype and knockout mice. In both permanent
      and transient occlusion paradigms, there were no statistically significant
      differences between wildtype and knockout mice in terms of 24 h ischemic lesion
      volumes. These data suggest that MMP-2 does not contribute to acute tissue damage
      in this model of focal ischemia.

PMID- 11588619
TI  - Corticosterone rapidly reduces male odor preferences in female mice.
AB  - There is accumulating evidence for rapid, non-genomic behavioral effects of
      various steroids including that of the glucocorticoid, corticosterone. Using an
      odor preference test, the responses of which are indicative of mate preferences
      and sexual interest, we examined the effects of acute corticosterone on the
      responses of oestrous female mice to male odors. Control female mice displayed an
      overwhelming preference for the odors of male mice. Peripheral administration of
      corticosterone elicited a significant dose-related (1.0-5.0 mg/kg) decrease in
      female preference for male odors at 10 min, but not at 60 min, after
      administration. These inhibitory effects of corticosterone on odor preferences
      were significantly reduced by the competitive NMDA antagonist, NPC 12626, and
      enhanced by the GABA antagonist bicuculline. This indicates that corticosterone
      has rapid inhibitory effects on olfactory mediated female mate preferences and
      responses to male odor that in part involve interactions with NMDA and GABA
      receptor mechanisms.

PMID- 11588621
TI  - Modelling eye diseases in zebrafish.

PMID- 11588622
TI  - Traumatic brain ischemia during neuro intensive care: myth rather than fact.
AB  - In non-missile severe acute brain trauma, brain ischemia was a frequent finding
      in cadavers. Studies during neuro intensive care, however, have failed to
      disclose brain ischemia under most circumstances, except when cerebral
      hemodynamic and metabolic parameters have been misinterpreted, or when cerebral
      blood flow (CBF) alone has been addressed in a biased fashion, without mandatory
      metabolic data. Indeed, comprehensive and unbiased studies focusing on global
      cerebral metabolic activity have invariably revealed a condition of normal
      coupling between reduced CBF and oxygen consumption in the early postinjury
      hours, which is then followed by a prolonged, sustained pattern of relative
      cerebral hyperperfusion (the opposite of ischemia). Accordingly, traumatic brain
      ischemia during intensive care represents myth rather than fact.

PMID- 11588623
TI  - Distant microglial and astroglial activation secondary to experimental spinal
      cord lesion.
AB  - This paper analysed whether glial responses following a spinal cord lesion is
      restricted to a scar formation close to the wound or they might be also related
      to widespread paracrine trophic events in the entire cord. Spinal cord
      hemitransection was performed in adult rats at the thoracic level. Seven days and
      three months later the spinal cords were removed and submitted to
      immunohistochemistry of glial fibrillary acidic protein (GFAP) and OX42, markers
      for astrocytes and microglia, as well as of basic fibroblast growth factor
      (bFGF), an astroglial neurotrophic factor. Computer assisted image analysis was
      employed in the quantification of the immunoreactivity changes. At the lesion
      site an increased number of GFAP positive astrocytes and OX42 positive phagocytic
      cells characterized a dense scar formation by seven days, which was further
      augmented after three months. Morphometric analysis of the area and
      microdensitometric analysis of the intensity of the GFAP and OX42
      immunoreactivities showed reactive astrocytes and microglia in the entire spinal
      cord white and gray matters 7 days and 3 months after surgery. Double
      immunofluorescence demonstrated increased bFGF immunostaining in reactive
      astrocytes. The results indicated that glial reaction close to an injury site of
      the spinal cord is related to wounding and repair events. Although gliosis
      constitutes a barrier to axonal regeneration, glial activation far from the
      lesion may contribute to neuronal trophism and plasticity in the lesioned spinal
      cord favoring neuronal maintenance and fiber outgrowth.

PMID- 11588624
TI  - Effects of protein and vitamin B deficiency on blood parameters and myenteric
      neurons of the colon of rats.
AB  - The aims of this work were to evaluate the effects of the deficient ingestion of
      protein and vitamin B on the biochemical and hematologic parameters and on the
      NADH- and NADPH-diaphorase positive myenteric neurons. The control animals (n=10)
      received commercial chow and the experimental rats (n=10) received chow with
      protein level reduced to 8% during 120 days. At the time of killing blood was
      collected for assessment of the blood and hematologic parameters and the
      ascending colon for quantitative analysis of the neurons of the myenteric plexus.
      It was observed that the reduction of the protein level to 8% coupled to the
      reduction of the levels of vitamin B in adult rats neither led to qualitative or
      quantitative changes on red or white blood cells, nor decreased globulin levels,
      induced the formation of edema or gave rise to clinical signs typical of protein
      or vitamin B deficiency. On the other hand, the experimental protocol led to less
      weight gain, change on the body composition with fat deposition; decrease of the
      values of serum total protein and albumin; reduction of the area of colon and
      density of nitrergic and NADH-diaphorase myenteric neurons inferior to the
      expected.

PMID- 11588625
TI  - Action of selective serotonin reuptake inhibitor on aggressive behavior in adult
      rat submitted to the neonatal malnutrition.
AB  - The effect of the malnutrition during suckling on the aggressiveness was
      investigated in adult rats treated or not with citalopram, a selective serotonin
      reuptake inhibitor (SSRI). The animals were divided into two groups according to
      the diet used: nourished group - the rats received the control diet with 23%
      protein during the life; and malnourished group - the rats had its mothers
      submitted to diet with 7.8% protein during suckling. At 120 days of age, each
      group was sub-divided according to the treatment: acute - consisting a single
      i.p. injection of saline solution or 20-mg/Kg citalopram; chronic - consisting
      the single injections (1 per day during 14 days) of saline or 20 mg/Kg
      citalopram. The acute or chronic treatment with SSRI reduces aggressive response
      in nourished rats, but not in malnourished ones. Thus, the malnutrition during
      the critical period of brain development seems to induce durable alterations in
      the function of the serotoninergic neurotransmission

PMID- 11588626
TI  - Prevalence and costs of headaches for the public health system in a town in the
      interior of the state of Sao Paulo.
AB  - Despite the high prevalence, impact and economic importance of headaches, studies
      on this subject are rare in Brazil. The aim of the present study was to estimate
      the prevalence of headaches in the public health system of a town in the interior
      of the State of Sao Paulo, as well as to estimate the costs resulting from its
      management. Data refer to the year of 1998 and were obtained according to the
      following steps: 1) territorial and demographic characterization of the
      municipality; 2) characterization of the financial indices and social well-being;
      3) budget characteristics of the municipality; 4) evaluation of the structuring
      of the medical service; 5) determination of the prevalence of headaches at
      different patient care levels; and 6) calculation of the costs of headaches.
      Headaches represented 7.9% of all visits at basic health units, 9.7% in the
      emergency room and 1.1% of hospital admissions. The total costs were R$ 85,131.31
      (US$ 70,942.76) corresponding to R$ 7.59 (US$ 6,32) per inhabitant/year. The
      present study shows the need for epidemiological and economic impact studies,
      which would provide the basis for the rational use of health funds.

PMID- 11588627
TI  - Primary progressive aphasia: analisys of 16 cases.
AB  - Primary progressive aphasia (PPA) is an intriguing syndrome, showing some
      peculiar aspects that differentiate it from classical aphasic pictures caused by
      focal cerebral lesions or dementia. The slow and progressive deterioration of
      language occurring in these cases provides an interesting model to better
      understand the mechanisms involved in the linguistic process. We describe
      clinical and neuroimaging aspects found in 16 cases of PPA. Our patients
      underwent language and neuropsychological evaluation, magnetic resonance imaging
      (MRI) and single photon emission computerized tomography (SPECT). We observed a
      clear distinction in oral expression patterns; patients were classified as fluent
      and nonfluent. Anomia was the earliest and most evident symptom in both groups.
      Neuroimaging pointed to SPECT as a valuable instrument in guiding the
      differential diagnosis, as well as in making useful clinical and anatomical
      correlations. This report and a comparison to literature are an attempt to
      contribute to a better understanding of PPA.

PMID- 11588628
TI  - Involuntary hand levitation associated with parietal damage: another alien hand
      syndrome.
AB  - The alien hand syndrome (AHS) usually consists of an autonomous motor activity
      perceived as an involuntary and purposeful movement, with a feeling of
      foreignness of the involved limb, commonly associated with a failure to recognise
      ownership of the limb in the absence of visual clues. It has been described in
      association to lesions of the frontal lobes and corpus callosum. However,
      parietal damage can promote an involuntary, but purposeless, hand levitation,
      which, sometimes, resembles AHS. In the present study, four patients (cortico
      basal ganglionic degeneration - n=2; Alzheimer's disease - n=1 and parietal
      stroke - n=1) who developed alien hand motor behaviour and whose CT, MRI and/or
      SPECT have disclosed a major contralateral parietal damage or dysfunction are
      described. These results reinforce the idea that parietal lobe lesions may also
      play a role in some patients with purposeless involuntary limb levitation, which
      is different from the classic forms of AHS.

PMID- 11588629
TI  - [Contributions to the neuropsychology of executive behavior: performance of
      normal individuals on the Tower of London and Wisconsin tests].
AB  - The concept of "executive behavior" encompasses a set of abilities which are
      critical for the organization of thought and behavior. To test the hypothesis
      that executive behavior is composed of multiple modules we investigated the
      performance of 61 normal adults on two widely used executive tasks, the Wisconsin
      Card Sorting (WCST) and the Tower of London (TOL) tests. We hypothesized that if
      executive behavior were composed of multiple modules, the main dimensions of each
      task would be weakly, if at all, statistically related. We also tested the
      hypothesis that occupational functioning would be related to executive
      performance. Our results revealed no significant association between the WCST and
      TOL tasks, favoring the idea that executive behavior is made up of multiple
      neuropsychological dimensions. Secondly, men fared significantly better than
      women on the difficult (4 and 5-moves) TOL puzzles. Finally, there was a
      significant association between performance on the difficult TOL puzzles and
      level of occupational functioning. These findings may explain certain
      dissociations in executive behavior commonly observed in patients with focal or
      diffuse brain damage. If replicated, they might be useful in the prediction of
      success in cognitive rehabilitation programs.

PMID- 11588630
TI  - Applicability of the CERAD neuropsychological battery to Brazilian elderly.
AB  - There is a limited choice of psychometric tests for Portuguese speaking people
      which have been evaluated in well defined groups. A Portuguese version of CERAD
      neuropsychological battery was applied to a control group of healthy elderly (CG)
      (mean age 75.1 years/ education 7.9 years), 31 Alzheimer disease (AD) patients
      classified by clinical dementia rating (CDR) as CDR1 (71.4/ 9.0) and 12 AD
      patients CDR 2 (74.1/ 9.3). Cut-off points were: verbal fluency-11; modified
      Boston naming-12; Mini-mental State Examination (MMSE) -26; word list memory-13;
      constructional praxis-9; word recall-3, word recognition-7; praxis recall-4.
      There was a significant difference between CG and AD-CDR1 (p<0.0001) for all
      tests. There was a less significant difference for constructional praxis and no
      difference for Boston naming. Comparison between AD-CDR1 and AD-CDR2 showed
      difference only for MMSE, verbal fluency, and Boston naming. The performance of
      CG was similar to that of a US control sample with comparable education level.
      These results indicate that this adaptation may be useful for the diagnosis of
      mild dementia but further studies are needed to define cut-offs for
      illiterates/low education people.

PMID- 11588631
TI  - [Quality of life in epilepsy and perception of seizures control].
AB  - The individual affective-cognitive evaluations are important factors that control
      the way he feels the disease impact in his life. Then, the perception of seizure
      control is a more important factor to evaluate Quality of Life (QoL) than the
      illness characteristics, such as the severity, type, sickening period and seizure
      frequency. This study searched for the relationship among the subjective
      variables (perception of seizure control) and the illness characteristics to
      evaluate QoL. The sample consisted of 60 individuals with chronic epilepsy, aging
      18 to 70 (M=37.05; SD=11.25), chosen at randon from the ambulatory of epilepsy -
      HC/UNICAMP, by the Questionnaire 65. The illness characteristics were not
      significant, except the seizures frequency, when associated to the impairment in
      QoL among controlled seizures and seizures with frequency higher than 10 per
      month (p=0.021). The perception of control was significantly associated to QoL
      (p=0.005).

PMID- 11588632
TI  - [Protocol of quality of life in epilepsy: preliminary results].
AB  - Seizures happen for brief periods of time, but the feelings of anxiety and
      helplessness, adaptation to the restrictions impose by the life-style and variety
      of other problems affect more the quality of life in epilepsy. This study
      proposes a protocol that regards the objectives of a quality of life assessment
      in health and is applied to a population that attends a university hospital. It
      contains 65 items and assesses the psychosocial performance, physical limitation,
      cognitive aspects, perception of control, self-concept, as well as perception of
      health and quality of life. The results of reliability and validity are
      discussed.

PMID- 11588633
TI  - [Anesthetic blockade of the greater occipital nerve in migraine prophylaxis].
AB  - Migraine comprises a great many encephalic structures in its pathophysiology with
      the trigeminal nerve (TN) type being one of the main ones. For the purpose of
      determining a possible influence of the greater occipital nerve (GON) on migraine
      behavior, 37 patients who showed this pathology were studied. Using a double
      blind "cross over" group and submitting those patients to a GON infiltration with
      bupivacaina 0.5% (BP) and physiological serum 0.9% (PS), the clinical effects
      were evaluated: subjectively, through a pain analytical visual scale;
      objectively, by determining the threshold of pain perception (algometry). The
      comparison between the two groups (BP-PS) and (PS-BP) has shown that the number
      and duration of the attacks did not show significant statistical differences
      during the study. The intensity of the attacks was lower in group (BP-PS) only
      after the second infiltration (p=0.020), in the other moments no differences have
      been observed between the groups. The conclusion is that the anesthetic blockage
      with BP on the GON does not change the number of crises and their duration, but
      it does provokes an intensity reduction after 60 days from the infiltration. The
      results shown here suggest that GON participates in the cranial nociceptive
      modulation during crises of migraine without aura.

PMID- 11588634
TI  - [Evaluation of placebo use in migraine without aura, migraine with aura and
      episodic tension-type headache acute attacks].
AB  - This study presents an evaluation of placebo response in the acute treatment of
      migraine with or without aura and episodic tension type headache. We studied
      patients admitted between March 1st,1997 and November 31st,1999 in two Emergency
      Room Units. Three groups had been defined, each one with 30 participants:
      migraine without aura (MWOA), migraine with aura (MWA) and episodic tension-type
      headache (ETTH). Patients were participating of a randomized study to evaluate
      efficacy of 4 different drugs; those randomized to receive placebo were included.
      We evaluated pain and associated symptoms. After one hour of placebo
      administration, 50% of MWOA patients, 23.3% of MWA and 26.7% of ETTH had
      presented pain relief. The mean of this relief, evaluated by the numerical pain
      scale, was 41.6%, 23.1% and 36%, respectively. Use of placebo is essential in
      evaluating the therapeutic role of drugs used in the treatment of acute headache.

PMID- 11588635
TI  - [Assessment of erectile dysfunction in patients with Parkinson's disease].
AB  - Thirty men having Parkinsons disease (PD) and 30 controls were studied
      prospectively by the use of the International Index of Erectile Function (IIEF)
      to assess erectile dysfunction (ED). Of the patients with PD (mean age of 59
      years), 46.66% referred to the practice of sexual activity. All of the
      parkinsonians were using antiparkinsonian medication. In the control group (mean
      age of 63 years), 76.66% referred to the practice of sexual activity, 46.60% to
      arterial hypertension and 6.66% to diabetes mellitus. The median score for the PD
      group according to the IIEF was 34, and that for the controls 50. The main
      differences between the two groups were in the erectile function, orgasmic
      function and satisfaction with the sexual relationship. The IIEF is a
      multidimensional scale widely accepted to assess the ED. The data obtained
      suggest that ED is more frequent among parkinsonians and points out to the role
      of DP in the genesis of ED.

PMID- 11588636
TI  - [Magnetic resonance imaging in multiple sclerosis: analysis of 270 cases].
AB  - The author report a retrospective study of 270 cases of clinically proved MS and
      MRI in a State of Brazil (Parana) which is localized between the parallels 22
      degrees a 30 degrees South. Comments are made about the age of the patients,
      number and localization of the lesions in the brain and spinal cord.

PMID- 11588637
TI  - [Relationships between the coronal suture and the sulci of the lateral convexity
      of the frontal lobe: neurosurgical applications].
AB  - An anatomical study of the relationships between the coronal suture and the sulci
      of the convexity of the frontal lobe was accomplished in seven cephalic segments.
      The pre-central and central sulci are, respectively, 26,5 mm and 40,5 mm behind
      the bregma and 15,0 mm and 35,5 mm behind the pterion. The use of the coronal
      suture as point of reference, and especially, its relationship with the sulci of
      the lateral surface of the frontal lobe, allows to determine the projection on
      the cranium of the superficial cerebral lesions with the purpose to delimit the
      surgical access and to guide the approach to the cerebral convexity.

PMID- 11588638
TI  - [Clinical subtypes of frontotemporal dementia].
AB  - Three distinctive clinical presentations can occur in frontotemporal dementia
      (FTD): disinhibited, apathetic and stereotypic subtypes. Each one shows a
      specific pattern of clinical, neuropsychological and neuroimaging findings,
      besides manifesting the core features of this form of dementia. We report three
      clinical cases, each one an example of a subtype of FTD, that were evaluated by
      neuropsychological and neuroimaging methods. Even the reported cases being a
      prototype of a specific subgroup, they can share some features with the others
      subtypes. According to this, patients with predominantly disinhibited or
      stereotypic behavior can also show apathy, in much the same way as predominantly
      apathetic or disinhibited patients can manifest stereotypic ritualistic behavior.
      The final stage of FTD is generally dominated by apathetic behavior.

PMID- 11588639
TI  - Amyloidotic muscle pseudohypertrophy: case report.
AB  - The authors report one case of amyloidosis associated with muscular
      pseudohypertrophy in a 46-year-old woman, who developed weakness, macroglossia
      and muscle hypertrophy associated with primary systemic amyloidosis.
      Electromyography showed a myopathic pattern and bilateral carpal tunnel syndrome.
      The muscle biopsy presented with a type I and II fiber hypertrophy and
      infiltration of amyloid material in the interstitious space and artery walls. She
      underwent bone marrow transplantation with stabilization and subjective
      improvement of the clinical picture.

PMID- 11588640
TI  - Complex phonic tic and disinhibition in Tourette syndrome: case report.
AB  - Tourette syndrome (TS) is a neuropsychiatric disorder characterized by a
      combination of multiple motor tics and at least one phonic tic. TS patients often
      have associated behavioral abnormalities such as obsessive compulsive disorder,
      attention deficit and hyperactive disorder. Coprolalia, defined as emission of
      obscenities or swearing, is one type of complex vocal tic, present in 8% to 26%
      of patients. The pathophysiology of coprolalia and other complex phonic tics
      remains ill-defined. We report a patient whose complex phonic tic was
      characterized by repetitively saying "breast cancer" on seeing the son of aunt
      who suffered from this condition. The patient was unable to suppress the tic and
      did not meet criteria for obsessive compulsive disorder. The phenomenology herein
      described supports the theory that complex phonic tics result from disinhibition
      of the loop connecting the basal ganglia with the limbic cortex.

PMID- 11588641
TI  - Cataleptic postures in thalamic hemorrhage: case report.
AB  - We report a case of catalepsy associated with thalamic hemorrhage. A 72 year-old
      hypertensive woman had acute onset of right-sided weakness and speech
      disturbances. She was on anticoagulants because of aortic valve replacement. When
      postures were imposed, the patient maintained the left upper limb raised for
      several minutes, even in uncomfortable or bizarre positions. A CT scan of the
      head revealed a left thalamic hemorrhage. Cataleptic postures have been reported
      in few cases with acute stroke.

PMID- 11588642
TI  - Spontaneous subarachnoid hemorrhage as the primary manifestation of carotid
      cavernous fistulas: case report.
AB  - We report the case of a 19-year old male patient initially admitted to our
      service after a motor vehicle accident with a normal neurologic evaluation and a
      CT scan that revealed no abnormalities. Nineteen months later, he was readmitted
      after a subtle headache episode, followed by a brief loss of consciousness. He
      was submitted to a complete evaluation, which revealed no abnormalities (even in
      the neurologic and ophthalmologic exams). A CT was performed revealing a diffuse
      subarachnoid hemorrhage. Contrast enhancement displayed a right paraselar lesion,
      which was first interpreted as a giant aneurysm. The patient underwent a cerebral
      angiography which showed a right carotid-cavernous fistula with retrograde venous
      drainage through the superior and inferior petrosal sinuses. Filling of various
      cortical vessels was observed. The patient was treated with endovascular
      technique and a control angiographic study assured the complete closure of the
      fistula. He had an excellent clinical recovery, being discharged in good
      conditions.

PMID- 11588643
TI  - Fatal rhabdomyolysis after acute sodium monensin (Rumensin) toxicity: case
      report.
AB  - Myoglobinuria or rhabdomyolysis occurs when myoglobin escapes into the blood and
      then into the urine after acute muscle necrosis. It can be a serious medical
      condition leading to renal failure and death. There are many causes including
      exertion, crush syndromes, ischaemia, metabolic disorders, exogenous toxins and
      drugs, heat stroke and hereditary disorders such as malignant hyperthermia. We
      report the case of a 17 year-old boy who developed myoglobinuria, renal failure
      and death 11 days after ingesting sodium monensin, possibly with the intention of
      developing muscles. Sodium monensin, the active principle of Rumensin(R), is a
      dietary additive used as a growth promoter for confined cattle. There are no
      previous reports of human intoxication. Accidental or experimental sodium
      monensin intoxication in animals produces similar findings to those seen in this
      case.

PMID- 11588644
TI  - [Ganglioglioma of the pineal region: case report].
AB  - Ganglioglioma are tumors presenting neoplastic glial cells and nerve cells, very
      rarely found in the pineal region. Only eight cases have been previously
      published in the literature. We present the case of a 14 years-old male patient
      with a ganglioglioma of the pineal region. The patient was treated surgically by
      a suboccipital transtentorial approach with complete removal. Histopathologic
      specimens with immunostaining revealed a ganglioglioma grade I. We conclude that
      these tumors are rare and should be treated surgically aiming total remove. If it
      is not possible or in case of reocurrence the patient should be followed and
      radiotherapy could be considered.

PMID- 11588645
TI  - [Relapsing polychondritis associated with meningoencephalitis: case report].
AB  - Polychondritis is a disease manifesting as an episodic inflammation of
      cartilagenous structures throughout the body with progressive course. We describe
      a patient with a presentation picture of two episodes of meningoencephalitis and
      after the outcome with polychondritis. Neurological involvement is rare in this
      disease as neurologic presenting symptoms do. The diagnostic precision was
      determinant for a satisfactory outcome with corticosteroids and methotrexate.

PMID- 11588646
TI  - [Involuntary movement disorders as first manifestation of systemic lupus
      erythematosus: case report].
AB  - We describe a 36 year-old woman who developed chorea two months after starting
      the use of oral contraceptives. She also developed thrombocytopenia, oral ulcers,
      arthritis, positive antinuclear antibodies (ANA), anti-Sm and anti-DNA, filling
      criteria for systemic lupus erythematosus, as defined by the American College of
      Rheumatology. The tests for lupus anticoagulant and anticardiolipin (IgG and IgM)
      were negative. The patient was treated with prednisone, phenitoin, phenobarbital
      and clonazepam, obtaining clinical and labatorial improvement. We discuss the
      ocurrence of chorea and other movement disorders as first manifestation of
      systemic lupus erythematosus, its relationship with oral contraceptives and
      antiphospholipid antibodies.

PMID- 11588647
TI  - [Segmental dystonia as manifestation of cavernous angioma: case report].
AB  - Dystonia is a neurologic syndrome whose etiology is not well recognized. We
      report a sixteen year old patient with difficulty in playing piano, with
      disability of the left hand, forearm and arm. Short after, she underwent
      "absence" crises and headache. Neuroradiological exams showed a deep temporal
      lobe cavernous angioma. It is a rare association between both diseases and there
      are no reports about segmental dystonia associated to pseudoabsence epilepsy and
      sporadic migraine secondary to cavernous angioma. Twenty five per cent of
      dystonias have a secondary cause and we suggest a neuroradiologic investigation.

PMID- 11588648
TI  - [Acute cerebellitis caused by Epstein-Barr virus: case report].
AB  - Acute cerebellitis can occur in association with varicella-zoster virus,
      enterovirus, mumps, mycoplasma, and other infective organisms. Acute cerebellitis
      is a rare complication of Epstein-Barr virus (EBV) infection. We report the case
      of a 21-year-old woman with a 12-day history of nausea and vomiting, gait and
      limbs ataxia, myoclonus, tremor of head and all four limbs, opsoclonus and
      cutaneous rash. Anti-EBV IgG and IgM antibodies against antiviral capsid were
      positive and anti-EBV against virus-associated nuclear antigen was also positive.
      EBV infection in association with neurological findings can occur without the
      classic signs and symptoms of infectious mononucleosis.

PMID- 11588649
TI  - [Constrictive arachnoiditis after pantopaque myelography causing syringomyelia
      and paraparesis: case report].
AB  - We present an unusual case of thoracic constrictive arachnoiditis after
      pantopaque myelography, used 10 years before in the diagnosis of intradural
      arachnoid cyst.

PMID- 11588650
TI  - [Meningiomas in pediatric patients: report of 2 cases].
AB  - Meningiomas correspond to 1% - 4% of primary intracranial tumors in pediatric
      group, with their incidence raising according to age. There is not gender
      prevalence, in spite of some authors describe a male tendency opposed to female
      one in adulthood. At present study we describe two cases of pediatric meningiomas
      reviewing clinical, radiological and histological aspects of these lesions. The
      authors review also treatment options and prognosis of childhood meningiomas. A
      two-year-old boy was admitted with seizures. Computerized tomography showed a
      right parietal lesion, which was totally resected. Histological features were
      compatible with meningioma. After 17 months the child is doing well, with no
      deficits or seizures. The second case is a 12-year-old girl, with a headache
      complain. During investigation, a CT revealed a right frontal lesion. She was
      operated under a right frontal craniotomy with total tumor resection. Nowadays
      she is asymptomatic, 20 months after surgery. Despite meningiomas in pediatric
      group are uncommon; they should be included in differential diagnosis list of
      expansive intracranial lesions of childhood.

PMID- 11588651
TI  - [Uncommon presentation of central neurocytoma causing intraventricular
      hemorrhage: case report].
AB  - Central neurocytoma was first described by Hassoun et al. in 1982 as a well
      differentiated tumor from neuronal origin. This tumor typically occurs in young
      adults, localized in the ventricular system. It usually presents as intracranial
      hypertension due to obstructive hydrocephalus. The differential diagnosis should
      be done with others intraventricular tumors as oligodendroglioma, subependymoma
      and choroidal plexus papilloma. There are few cases of central neurocytoma
      presented by intraventricular hemorrhage in the literature. We report a case of
      35 year-old woman, who presented with obstructive hydrocephalus due to
      intraventricular hemorrhage within the tumor. MRI revealed a tumor localized in
      the right lateral ventricle. Histopathological and immunohystochemical analysis
      confirmed the diagnosis of central neurocytoma. We review options for the
      treatment of this entity as well reinforce the inclusion of central neurocytoma
      as a differential diagnosis for intraventricular hemorrhage.

PMID- 11588652
TI  - [Contributions of Charcot and Marsden to the development of movement disorders in
      the 19th and 20th centuries].
AB  - Charcot described many neurological diseases in the 19th century, particularly in
      movement disorders. Charcot contributed in the clinical description of
      Parkinson's disease, and introduced its first pharmacological treatment. He also
      studied the hyperkinesias, e.g. of Tourette syndrome, differential diagnosis of
      tremors, dystonias, choreas and startle disease. Marsden, who died recently, was
      an exponent in the study of Movement Disorders, with many publications in this
      field in the 20th century. His most important contributions are definitions and
      classifications of movement disorders, such as Parkinson's disease, dystonia,
      myoclonus, essential tremor, the description of the syndromes "Painful Legs
      Moving Toes", "Gait Ignition Failure" and "Primary Writing Tremor". The
      contributions of Charcot in the 19th century and Marsden in the 20th century to
      the movement disorders allow us to conclude that both of them were the most
      representative icons in this field in the past two centuries.

PMID- 11588653
TI  - Antidepressants in social anxiety disorder.
AB  - Social anxiety disorder (SAD) is a marked and persistent fear of doing almost
      everything in front of people due to concerns about being judge by others. An up
      to-date review is needed in order to reach a practical judgement of all
      psychopharmacological data. Case reports, open and double-blind trials with SAD
      were described and commented upon from a clinical point of view. The MEDLINE
      system was searched from 1975 to 2001. The references from the selected papers
      were also used as a source. MAOIs (fenelzine, tranylcypromine), reversible
      monoamino oxidase-A inhibitors (moclobemide, brofaromine), SSRIs (paroxetine,
      sertraline, fluoxetine, fluvoxamine) and some other antidepressants (venlafaxine,
      nefazodone) have proven effective in several studies with various methodologies.
      The MAOIs have more serious adverse effects and the SSRIs have the best
      tolerance. SSRIs are efficacious and the first choice of treatment.

PMID- 11588655
TI  - The brain and somatic integration: insights into the standard biological
      rationale for equating "brain death" with death.
AB  - The mainstream rationale for equating "brain death" (BD) with death is that the
      brain confers integrative unity upon the body, transforming it from a mere
      collection of organs and tissues to an "organism as a whole." In support of this
      conclusion, the impressive list of the brain's myriad integrative functions is
      often cited. Upon closer examination, and after operational definition of terms,
      however, one discovers that most integrative functions of the brain are actually
      not somatically integrating, and, conversely, most integrative functions of the
      body are not brain-mediated. With respect to organism-level vitality, the brain's
      role is more modulatory than constitutive, enhancing the quality and survival
      potential of a presupposedly living organism. Integrative unity of a complex
      organism is an inherently nonlocalizable, holistic feature involving the mutual
      interaction among all the parts, not a top-down coordination imposed by one part
      upon a passive multiplicity of other parts. Loss of somatic integrative unity is
      not a physiologically tenable rationale for equating BD with death of the
      organism as a whole.

PMID- 11588656
TI  - A requiem for whole brain death: a response to D. Alan Shewmon's 'the brain and
      somatic integration'.
AB  - Alan Shewmon's article, 'The brain and somatic integration: Insights into the
      standard biological rationale for equating "brain death" with death' (2001),
      strikes at the heart of the standard justification for whole brain death
      criteria. The standard justification, which I call the 'standard paradigm', holds
      that the permanent loss of the functions of the entire brain marks the end of the
      integrative unity of the body. In my response to Shewmon's article, I first offer
      a brief summary of the standard paradigm and cite recent work by advocates of
      whole brain criteria who tenaciously cling to the standard paradigm despite
      increasing evidence showing that it has significant weaknesses. Second, I address
      Shewmon's case against the standard paradigm, arguing that he is successful in
      showing that whole brain dead patients have integrated organic unity. Finally, I
      discuss some minor problems with Shewmon's article, along with suggestions for
      further elaboration.

PMID- 11588657
TI  - Clarifying the discussion on brain death.
AB  - Definitions of death are based on subjective standards, priorities, and social
      conventions rather than on objective facts about the state of human physiology.
      It is the meaning assigned to the facts that determines when someone may be
      deemed to have died, not the facts themselves. Even though subjective standards
      for the diagnosis of death show remarkable consistency across communities, they
      are extrinsic. They are driven, implicitly or explicitly, by ideas about what
      benefits the community rather than what benefits the individual. The differences
      that do exist across communities generally reduce to questions about legitimacy
      and not fact. The questions at the core of the debate about brain death are
      better framed by asking: "Whom ought we deem to be dead?" rather than: "Who is
      dead." The rationale for equating brain death with death, therefore, extends well
      beyond somatic and biological concepts of death.

PMID- 11588658
TI  - Philosophical debates about the definition of death: who cares?
AB  - Since the Harvard Committee's bold and highly successful attempt to redefine
      death in 1968 (Harvard Ad Hoc committee, 1968), multiple controversies have
      arisen. Stimulated by several factors, including the inherent conceptual weakness
      of the Harvard Committee's proposal, accumulated clinical experience, and the
      incessant push to expand the pool of potential organ donors, the lively debate
      about the definition of death has, for the most part, been confined to a
      relatively small group of academics who have created a large body of literature
      of which this issue of the Journal of Medicine and Philosophy is an example. Law
      and public policy, however, have remained essentially unaffected. This paper will
      briefly review the multiple controversies about defining death in an attempt to
      explain why they have and will remain unresolved in the academic community and
      have even less chance of being understood and resolved by politicians,
      legislators, and the general public. Considering this, we will end by suggesting
      the probable course of public policy and clinical practice in the decades ahead.

PMID- 11588659
TI  - [Effect of cyclosporin A on renal function in patients with glomerulonephritis].
AB  - BACKGROUND AND OBJECTIVE: Cyclosporin A ( CsA) plays a confounding part in the
      treatment of nephrotic syndrome. Renal hemodynamics and glomerular
      permselectivity were investigated in patients with glomerulonephritis to analyse
      the antiproteinuric action of CsA and to differentiate between nephrotoxic and
      immunosuppressive effects. METHODS: We studied 19 patients with nephrotic
      syndrome after 6 months of treatment with CsA (membranous glomerulonephritis-MGN,
      n = 10; focal segmental sclerosing glomerulonephritis - FSGN, n = 5; minimal
      changes glomerulonephritis - MCGN, n = 4). Patients were studied three times
      within 3 weeks with (A) and without (B) CsA treatment (A-B-A'). Blood pressure,
      creatinine, proteinuria, C(In), C(PAH), C(Dex) were measured (analysis according
      to the model of Deen et al., Am J Physiol. 1985; 249 : 374). RESULTS: GFR (C
      (In)) increased significantly after withdrawal of CsA from 54 +/- 7.3 to 64 +/-
      8.5 ml/min (p < 0.01). Proteinuria increased after withdrawal of cyclosporin (B)
      between 21 % (MGN) and 45 % (FSGN). After withdrawal of CsA (B) there was no
      change of FC(dex) in patients with MGN and FSGN. Withdrawal of CsA in patients
      with MCGN induced a significant decrease in glomerular selectivity in the high
      molecular range. CONCLUSION: These data demonstrate that CsA is able to induce
      even in the short term a significant increase in glomerular permselectivity in
      MCGN. The acute effects on GFR predominantly determined the acute antiproteinuric
      effects in patients with MGN and FSGN.

PMID- 11588660
TI  - [Pneumatosis cystoides intestinalis, a rare complication of mixed connective
      tissue disease].
AB  - HISTORY AND ADMISSION FINDINGS: A 77-year-old woman presented with diarrhoea and
      increasing malaise. The patient reported a weight loss of 30 kilogram over the
      past 12 months due to recurrent episodes of diarrhoea. During previous
      hospitalisations the diagnosis of a mixed connective tissue disease had been
      established, and the patient was treated with azathioprine and prednisolone.
      Clinical findings at presentation included diffuse oedema of the hands, Raynaud's
      and Sicca syndrome, dysphagia and a distended abdomen and pain on palpation of
      the left lower abdomen. INVESTIGATIONS: A chest X-ray revealed pneumoperitoneum.
      Contrast medium radiography of gastro-intestinal passage and an abdominal CT with
      contrast medium confirmed the existence of pneumoperitoneum and showed, in
      addition, intramural gas in the wall of the dilated jejunum. No contrast medium
      leakage as an indicator of an open perforation was detectable. DIAGNOSIS,
      TREATMENT AND CLINICAL COURSE: Due to suspected encapsulated perforation a
      laparotomy was performed. In situ, multiple gas bubbles were found both in the
      bowel walls and in the mesentery. The small intestine was severely distended,
      atonic but without evidence for a stenosis. In the absence of an open
      perforation, the diagnosis of pneumatosis cystoides intestinalis (PCI) was
      established as the underlying cause of the pneumoperitoneum. Treatment with
      metronidazole was initiated and the diarrhoea resolved over the following 3
      weeks. CONCLUSION: PCI is a rare condition, to be considered if pneumoperitoneum
      is present. One possible underlying cause is an intestinal manifestation of a
      mixed connective tissue disease.

PMID- 11588661
TI  - [Urinary tract infection - Case report].

PMID- 11588662
TI  - [Urinary tract infection - diagnosis].

PMID- 11588663
TI  - [Urinary tract infection - treatment].

PMID- 11588666
TI  - [Fitness to fly of patients with lung disease].

PMID- 11588667
TI  - [Medical aspects of fitness to be remanded in custody or be imprisoned].

PMID- 11588668
TI  - [Request for hospital discharge records by insurance carriers--position of the
      federal officer for data protection].

PMID- 11588669
TI  - [Abdominal aortic aneurysm in surgical indications].

PMID- 11588670
TI  - [Hand, foot, mouth disease].

PMID- 11588671
TI  - 22nd Symposium of the AGNP. Nuremberg, September 26-29, 2001. Abstracts.

PMID- 11588672
TI  - [Radiologic screening for lung cancer: present status and future perspectives].
AB  - Radiologic screening for lung cancer: present status and future perspectives.
      Lung cancer is the most common cause of death from malignancy. This is
      predominantly due to the poor prognosis of the mostly advanced tumor stages at
      the time of presentation. Prognosis of early, usually asymptomatic stages is more
      favourable, particularly in non-small-cell histologic types. Therefore, early
      detection using diagnostic tests promises reduction of mortality from lung
      cancer. Due to its high sensitivity for small pulmonary nodules - the most common
      manifestation of early lung cancer - computed tomography appears suitable as a
      screening test particularly as the high radiation exposure associated with
      standard examination protocols can be significantly reduced for this purpose. Due
      to the high prevalence of benign small pulmonary nodules diagnostic algorithms
      are required for non-invasive classification of detected nodules. Preliminary
      studies of low-dose CT using algorithms based on size and density of detected
      nodules revealed a high proportion of asymptomatic lung cancers and early
      resectable tumor stages with a small number of invasive procedures for benign
      nodules. Prior to a wide application of this technique in clinical routine more
      data is required as to appropriate inclusion criteria, screening intervals and
      most importantly the effect of screening on reduction of mortality from lung
      cancer.

PMID- 11588673
TI  - Magnetic resonance imaging of the lung with a volumetric interpolated 3D-gradient
      echo sequence.
AB  - OBJECTIVE: To evaluate the feasibility of a magnetic resonance imaging protocol
      for the lung using a volumetric interpolated 3D-gradient echo sequence (3D-GRE).
      SUBJECTS AND METHODS: A T(1)-weighted 3D-GRE sequence was used for volumetric
      interpolated breath-hold examinations ("VIBE") of the lung in twelve healthy
      volunteers (TR/TE 4.5/1.9 ms, flip-angle 12 degrees, matrix 502 X 512
      [interpolated]). Three coronal 80 mm slabs (16 aportitions, 2.5 mm slices) were
      added to 3D data sets for multi-planar reformations. No contrast material was
      applied. Artifacts and resolution o vessel and airway structures in each lung
      segment were evaluated by two observers (12 volunteers, 228 lung segments).
      RESULTS: The protocol provided excellent images of vascular and tracheo-bronchial
      structures with very moderate pulsation artifacts. 224/228 lung segments were
      imaged with "good" (146/228) or "sufficient" quality (78/228). Segmental and sub
      segmental vessels (5th order) were identified due to bright flow signal without
      administration of contrast material. Walls of segmental bronchi (3rd order) were
      delineated in all parts of the lung. CONCLUSIONS: The high spatial resolution,
      the excellent visualization of lung anatomy, the low rate of artifacts without
      respiratory triggering and the short acquisition times are clear advantages of
      the 3D-GRE (VI-BE) sequence compared to existing 2D-GRE strategies for MRI of the
      lung.

PMID- 11588675
TI  - [Advanced breast biopsy instrumentation (ABBI) experiences and critical
      comments].
AB  - Advanced breast biopsy instrumentation (ABBI) experiences and critical comments.
      PURPOSE: To describe our three-years' experience with advanced breast biopsy
      instrumentation (ABBI). MATERIALS AND METHODS: Considering lesion size, type and
      location as well as patient specific criteria 89 patients were selected for an
      ABBI. The documented data like duration, complication and change of the
      procedure, size of the lesions and biopsy cannulas, histologic outcome and
      further treatment were analysed retrospectively. RESULTS: ABBI was successful in
      63 of 89 patients. Cancer was found in 18 patients (29 %) with a surgical re
      excision to achieve tumour-free margins in 89 %. 45 patients had benign lesions
      (71 %) with a benign to malignant ratio of 2.5 : 1. ABBI was unsuccessful or had
      to be replaced by other biopsy techniques in 26 patients (29 %). In four of these
      patients the localization needle was already placed. Analysing the three-year
      period ABBI frequency dropped each year with an overall reduction of 63 %.
      Despite a good benign to malignant ratio the surgical re-excision rate in cancer
      patients is disappointing. Although using precise selection criteria for ABBI the
      rate of failed biopsies and changeover to another biopsy procedure was too high.
      The reduction of ABBI procedures during the three-year period is assumed to be an
      expression of the negative experiences with the method but also a refusal of the
      assigning colleagues to use ABBI. CONCLUSION: For the evaluation of suspected
      breast lesions ABBI is too invasive and too expensive. On the other hand ABBI is
      too ineffective as a therapeutic tool to remove suspected lesions. Therefore it
      is not warranted to use ABBI instead of other concurrent biopsy techniques.

PMID- 11588676
TI  - [Cost-effectiveness of MR-imaging in the preoperative work-up of suspicious
      breast lesions].
AB  - Cost-effectiveness of MR-imaging in the preoperative work-up of suspicious breast
      lesions. PURPOSE: To assess the clinical and economic consequences of a
      preoperative magnetic resonance mammography (MRM) in patients with suspicious
      breast lesions. PATIENTS AND METHODS: 483 out of 2426 patients operated because
      of breast neoplasms at the University Hospital of Jena between August 1995 and
      March 1999 underwent preoperative Gd-enhanced breast MRI in addition to
      mammography and breast ultrasound because of suspicious breast lesions. The
      histological assessment was correlated with the results of the diagnostic imaging
      work-up in 447 cases. The costs of surgery for malignant lesions were calculated
      based on case- dependent billing agreements, costs of surgery of benign lesions
      were calculated based on current billing procedure. In 36 cases no surgery was
      performed due to the exclusion of malignancy by breast MRI. 140 benign lesions
      were treated surgically in spite of negative breast MRI diagnosis. The
      hospitalization time related costs caused by these cases were compared to the
      costs of preoperative MR-imaging. RESULTS: The total costs for MR mammography in
      all 483 patients amounted to DM 499,857. In 11 cases false positive results in
      MRM led to additional costs of DM 32,565. Assuming that there is no need for
      surgical treatment of benign breast lesions, total savings of DM 521,048 due to
      avoided hospitalization in 176 cases could have been possible. The savings per
      patient amount in these 176 cases are DM 2,960.50 compared to DM 1,034.90 costs
      for breast MRI. CONCLUSION: Despite the currently still high costs of breast MRI
      a major cost reduction can be achieved by prevention of unnecessary surgery,
      avoidance of additional surgery and associated trauma for patients.

PMID- 11588674
TI  - [The influence of motion artifacts conditioned by reconstruction, on the coronary
      calcium score in multislice spiral CT].
AB  - The influence of motion artifacts conditioned by reconstruction, on the coronary
      calcium score in multislice spiral CT. PURPOSE: A major problem of the
      quantification of coronary calcifications is a high variability of the coronary
      calcium score between recurrent examinations and different observers. Aim of our
      study is to evaluate the influence of different RR-intervals on the coronary
      calcium score utilizing retrospectively gated Multislice Spiral CT (MSCT) data
      sets. MATERIALS AND METHOD: 50 consecutive patients underwent MSCT examination
      (Somatom Volume Zoom, Siemens, Forchheim, G) utilizing a standardized scan
      protocol (4 x 2.5 mm collimation, 3 mm increment, tube current 133 mAs, tube
      voltage 120 kV). Retrospectively gated image reconstruction was performed every
      10 % of the RR interval. Coronary calcification was evaluated by the Agatston
      score. Coronary risk assessment was performed in all patients with image
      reconstruction beginning at 80 % of the RR interval. The reconstruction intervals
      with the least motion artifacts were identified and chosen as reference for a
      reevaluation of the coronary risk. The results of different reconstruction times
      were compared. RESULTS: The mean calcium score was 551.6. The calcium score
      varied between 512.2 (90 %) and 571.7 (70 %), depending on the image
      reconstruction interval. Compared to the mean calcium score a new classification
      of the coronary risk was necessary in 7/50 of the patients at 80 % reconstruction
      interval, and in 2/50 of the patients at 50 % of the RR interval, respectively.
      CONCLUSION: Movement of the coronary arteries at different image reconstruction
      intervals has an important influence on the coronary calcium score. Based on our
      data, we propose image reconstruction at 50 % of the RR interval for evaluation
      of the coronary calcium score by MSCT.

PMID- 11588677
TI  - [MR-morphological changes of the metacarpophalangeal joints in patients with
      rheumatoid arthritis: Comparison of early and chronical stages].
AB  - MR-morphological changes of the metacarpophalangeal joints in patients with
      rheumatoid arthritis: Comparison of early and chronical stages. PURPOSE:
      Evaluation of MRI findings in the metacarpophalangeal (MCP) joints in patients
      with early (eRA) and chronical rheumatoid arthritis (cRA). MATERIAL AND METHODS:
      In 22 RA patients (9 with disease duration </= 1.5 years = eRA) the dominant
      hands were examined by MRI in coronal T(2) weighted turbo-spin-echo (TSE). T(1)
      weighted spin-echo (SE) sequences before and after injection of Gd-DTPA and fat
      suppressed short tau inversion recovery (STIR) sequences, followed by
      miniarthroscopy (MA) of the MCP II joint after an interval of 24 hours. MRI and
      MA findings were assessed using standardised semiquantitative items of synovial
      and bony pathologies and a statistical comparison between eRA and cRA patients
      was performed. RESULTS: In MRI synovial proliferation was detected in 13/13 cRA
      and 8/9 eRA patients. It was statistically not significant; the degree of
      synovial proliferation was however lower in the eRA group. All eRA patients with
      synovial changes showed enhancement after administration of contrast medium, a
      marker which correlated with the clinical activity. In 2/13 cRA patients no
      uptake of contrast medium was evident. Bony erosions and strongly narrowing joint
      space correlated with disease duration and were documented significantly rarer in
      the eRA patients (1/9, 2/9) than in the cRA patients (9/13, 10/13). CONCLUSION:
      In RA patients, MRI of the metacarpophalangeal joints can detect specific
      pathological changes which are observed significantly more often in either early
      or chronic stages and which are associated with disease activity and duration.

PMID- 11588678
TI  - [Arterial steal syndrome in patients after liver transplantation: transarterial
      embolization of the splenic and gastroduodenal arteries].
AB  - Arterial steal syndrome in patients after liver transplantation: transarterial
      embolization of the splenic and gastroduodenal arteries. PURPOSE: To evaluate
      transarterial embolization of splenohepatic and gastroduodenal steal syndrome in
      patients with impaired liver function tests after liver transplantation. METHODS
      AND MATERIAL: In a prospective study 22 patients (10 male, 12 female; mean age
      49.5 years) with unexplained elevation of hepatic enzymes after liver
      transplantation underwent transcatheter arterial embolization of splenohepatic (n
      = 18) and gastroduodenal (n = 4) steal syndrome with use of Gianturco coils or
      microcoils. Liver and spleen parenchyma were surveyed and evaluated before and
      after embolization with plain helical CT, including volumetry of liver and
      spleen. RESULTS: DSA examinations revealed a dilated splenic artery (n = 18) or
      gastroduodenal artery (n = 4) combined with a slightly decreased perfusion of the
      hepatic arteries, while immediately after successful embolization a normal
      perfusion of the hepatic arteries could be noted. Volumetric measurements before
      and after embolization showed no significant changes in liver parenchyma (x = + 7
      % +/- 2), and variable changes in splenic volume of -5 % to + 28 % (mean, + 11
      %), with initial measurements. Clinical follow-up examinations revealed a
      normalization of the previously elevated hepatic enzymes and a normalization of
      liver function tests after successful embolization. Complications were observed
      in 4 patients (infarction of the spleen). CONCLUSIONS: The preliminary results
      reveal that in liver transplant candidates with splenohepatic and gastroduodenal
      steal syndrome successful embolization results in an improvement of organ
      perfusion with normalization of function tests.

PMID- 11588679
TI  - [Radiological-guided liver-port implantation: Evaluation, technical approach,
      interventional procedure and follow up].
AB  - Radiological-guided liver-port implantation: Evaluation, technical approach,
      interventional procedure and follow up. PURPOSE: Description of evaluation,
      technical approach, interventional procedure and follow up of radiological-guided
      liver-port implantation. METHOD: Percutaneous implantation of a liver-port system
      was performed in twelve patients through a transfemoral approach and in one
      patient via the superficial epigastric artery after surgical exploration. In four
      patients we used port systems which are accessible via ventral puncture. Strecker
      port systems were implanted in the remaining nine patients. RESULTS: The liver
      port implantation was technically successful in all cases. No dislocation of the
      distal catheter tip, no thrombosis of the hepatic or splenic artery, no leakage
      near connections of the catheters or connections of catheter and port system and
      no thrombosis of the femoral arteries were observed. Correction of a kink in the
      catheter was performed in one patient. Another patient showed prolonged healing
      of the subcutaneous pocket. CONCLUSIONS: Interventional liver-port implantation
      is a safe procedure and leads to good clinical results. From the view of the
      radiologist the Strecker-system shows a good performance. The approach via the
      superficial epigastric artery demands excellent interdisciplinary cooperation.

PMID- 11588680
TI  - [CT-guided thoracal sympathicolysis for the treatment of peripheral arterial
      occlusive disease and chronic thoracal pain syndromes in 6 patients].
AB  - CT-guided thoracal sympathicolysis for the treatment of peripheral arterial
      occlusive disease and chronic thoracal pain syndromes in 6 patients. PURPOSE:
      Retrospective evaluation of the safety and effectivity of CT-guided percutaneous
      thoracal sympathicolysis (CT-TSL) in the treatment of patients with peripheral
      arterial occlusive disease (PAOD) of the upper limb and chronic thoracal pain
      syndromes. Comparison of our own experience with literature reports. MATERIAL AND
      METHODS: Between 6/96 and 12/99, 4 patients with PAOD of the upper limb and two
      with chronic thoracal pain syndromes caused by herpes zoster were treated by
      unilateral CT-TSL. RESULTS: 18, 21 and 32 months after the intervention 3 out of
      4 patients treated for PAOD reported subjective improvements, and one remained
      unchanged. Two patients treated for pain syndromes showed no long-term benefit of
      the procedure. There were no serious complications. CONCLUSION: The CT-TSL is an
      alternative method in the treatment of PAOD in patients who are unsuitable for
      treatment by revascularization.

PMID- 11588681
TI  - [Simon nitinol vena cava filters: effectiveness and complications].
AB  - Simon nitinol vena cava filters: effectiveness and complications. PURPOSE: The
      aim of this retrospective analysis was to evaluate the clinical safety and
      effectiveness of the Simon Nitinol inferior vena cava filter (SNF) for prevention
      of pulmonary embolism. PATIENTS AND METHODS: 117 patients (63 male, 54 female;
      aged 58.38 +/- 14.59 years) underwent percutaneous implantation of an SNF from
      1993 through 1999. Patient reports were retrospectively analysed for
      complications during and after implantation and deep venous thrombosis (DVT) and
      pulmonary embolism before and after implantation. Helical-CT with contrast media
      and plain abdominal radiography were performed on 35 patients, helical-CT alone
      on two patients. We checked the position and configuration of the SNF and looked
      for a perforation of the filter legs through the wall of the inferior vena cava
      (IVC). The IVC and deep pelvic veins were analysed for patency. RESULTS: During
      implantation 10 of 117 (9 %) patients had minor complications, major
      complications were reported in 0.9 % (1/117). There was no significant increase
      in thrombosis of the deep pelvic veins and the IVC after implantation. Pulmonary
      re-embolism (PE) was documented in 9 out of 117 patients (7.7 %). One out of the
      35 examined patients (2.9 %) showed a single strut fracture of the SNF. Tilting
      more than 15 degrees was seen in 7 out of 37 patients (19 %). Dislocation of the
      SNF more than 10 mm occurred in one out of 35 patients (2.9 %), perforation
      through the wall of the IVC in all 37 patients. We found no occlusion of the IVC.
      CONCLUSION: The SNF is easy and safe to implant and successfully prevents
      pulmonary embolism. In our study the rate of well documented pulmonary re
      embolism (7.7 %) is satisfactory. Except for the high perforation rate through
      the wall of the IVC (100 %, but without clinical relevance), complication rates
      during and after implantation of the SNF are low compared with other filter
      types.

PMID- 11588682
TI  - [Gaucher disease: MR evaluation of bone marrow features during treatment with
      enzyme replacement].
AB  - PURPOSE: Enzyme replacement therapy (ERT) arrests and reverses the hematological
      and visceral symptoms of adult Gaucher disease, the most frequent lysosomal
      storage disorder. There are only a few studies available evaluating bone disease
      during ERT. The aim of this study was to investigate the features of bone marrow
      (bm) by magnetic resonance imaging (MRI) in these patients during ERT. MATERIALS
      AND METHODS: MRI was performed prospectively in thirty adult type I Gaucher
      patients before and during ERT with a mean follow-up of 3 years. Spin-echo
      sequences (T(1)/T(2)) of the lower extremities were obtained and the reconversion
      (response) or lack of reconversion (non-response) to fatty marrow during
      treatment was analyzed. The morphological features of bm involvement, a
      homogeneous or non-homogeneous distribution of bm changes and focal bone lesions
      surrounded by a rim of reduced signal intensity (SI), were analyzed. RESULTS:
      Infiltration of bm by Gaucher cells is characterized by a reduction of SI on both
      T(1)- and T(2)-weighted sequences. Bone marrow responses were seen in 19 patients
      (63 %) during treatment. Focal bone lesions, surrounded by a rim of reduced SI,
      did not respond to ERT and correlated with a non-homogenous distribution of bone
      involvement and splenectomy. CONCLUSION: In adult patients with type I Gaucher
      disease receiving ERT, treatment effects on bone disease can be demonstrated by
      MRI using Spin-echo sequences due to the partial reconversion of fat marrow. A
      non-homogeneous type of signal appearance and a status post splenectomy correlate
      with the presence of bone infarcts.

PMID- 11588683
TI  - [Impact of different iodine concentrations on abdominal enhancement in biphasic
      multislice helical CT (MS-CT)].
AB  - Impact of different iodine concentrations on abdominal enhancement in biphasic
      multislice helical CT (MS-CT). PURPOSE: To evaluate if different iodine
      concentrations of a contrast material (c.m.) have an impact on abdominal
      enhancement in MS-CT during the arterial (AP) and portal venous phase (PVP).
      MATERIALS AND METHODS: 75 patients underwent biphasic CT of the abdomen. They
      were assigned to three equally sized groups. For all patients a non-ionic c.m.
      (iopromide, Ultravist, Schering AG, Berlin) with different iodine concentrations
      and a constant total iodine load of 37 g with an injection flow rate of 4 ml/s
      was used. The volume of the c.m. differed depending on the iodine concentrations:
      group 1 (123 ml of 300 mgl/ml); group 2 (112 ml of 335 mgl/ml); group 3 (100 ml
      of 370 mgl/ml). The scan delay was optimized by using a bolus tracking device.
      The groups were compared concerning their mean enhancement of aorta, spleen,
      pancreas, and liver in the AP and PVP. RESULTS: The comparison of the three
      groups showed an improved enhancement in aorta, spleen, and pancreas during the
      AP by using the higher c.m. concentrations. In the PVP the c.m. enhancement of
      aorta, liver, spleen, and pancreas was independent of the administered c.m.
      concentration. CONCLUSION: Higher iodine concentrations of c.m. have a positive
      impact on abdominal enhancement during the AP. The concentration has no influence
      on the enhancement during the PVP of abdominal MS-CT.

PMID- 11588684
TI  - [Comparison of digital selenium radiography with an analog screen-film system in
      the diagnostic process of pneumoconiosis according to ILO classification].
AB  - Comparison of digital selenium radiography with an analog screen-film system in
      the diagnostic process of pneumoconiosis according to ILO classification.
      PURPOSE: The aim of the study was to determine the diagnostic value of digital
      selenium radiography in patients with pneumoconiosis. For this purpose chest x
      rays by digital selenium radiography and analog screen-film system were compared
      according to the ILO classification of pneumoconiosis. METHOD: After approval of
      the study by the local ethic commission and the Federal German Office for
      Radiation Protection 50 patients were subjected to x-rays by digital selenium
      radiography (Thoravision; Philips Medical Systems, Hamburg, Germany) and analog
      screen-film system of the same day within the scope of an industrial medicine
      preventive checkup. Four investigators rated the chest x-rays according to the
      ILO classification of pneumoconiosis. RESULTS: The findings demonstrated by chest
      x-rays according to ILO classification were rated similar by digital selenium
      radiography and analog screen film systems. Image quality of the digital pictures
      was rated significantly better. CONCLUSION: The use of digital selenium
      radiography in evaluating chest x-rays according to the ILO classification does
      not result in over- or underestimation of pulmonary pathologies. Hence, in the
      diagnosis of pneumoconiosis, digital selenium radiography can replace the tested
      analog screen-film system.

PMID- 11588685
TI  - [Artifacts in MR Imaging due to ventilation tubes].
AB  - Artifacts in MR Imaging due to ventilation tubes. PURPOSE: MR examinations may be
      necessary in patients under artificial ventilation. Possible imaging artifacts
      originating from ventilation tubing made from silicone are demonstrated.
      MATERIALS AND METHODS: In silicone carbohydrate residues are bound to silicon
      atoms. In silicone gels they give strong signals in MR imaging. MR signals from
      more solid silicone rubber are only possible if the carbohydrate residues in the
      molecular chain retain a sufficient mobility. To investigate whether silicone
      tubes give signals in MR images, different tubes for ventilation made from
      silicone and polyester were examined at 1.5 T (Gyroscan ACS NT, Powertrak 6000
      gradients) with MR imaging and spectroscopy (MRS: PRESS, TE = 20 ms; relaxation
      time measurements: MIXED sequence; imaging: FFE [gradient echo] and TSE
      sequences). RESULTS: Using short TE (</= 4 ms), tubes and sockets made from
      silicone could be imaged with FFE and SE sequences. An SE sequence with a short
      TE = 4 ms provided a sufficient signal intensity to depict the tube clearly
      besides brain tissue of a volunteer. When foldover occurred, the signal of the
      tube was projected onto the brain tissue. MR spectra confirmed that the image
      signal originated from the carbohydrate residues of the silicone molecule chains,
      not from residual water in the tube wall material. T(2) determinations indicate a
      multiexponential relaxation including a large component with a short TE (</= 15
      ms). Tubes made from a polyester elastomere did not show up in MR images.
      CONCLUSION: In MR images acquired with very short echo times silicone in
      ventilation tubes may produce significant artifacts.

PMID- 11588686
TI  - [Mechanical brush-catheter abrasion method for the isolation and culture of human
      umbilical vein endothelial cells. First in vitro results].
AB  - Mechanical brush-catheter abrasion method for the isolation and culture of human
      umbilical vein endothelial cells. First in vitro results. PURPOSE: To determine
      the value of a nylon brush (Cragg thrombolytic catheter system) with regard to
      the isolation and culture of viable human vascular umbilical vein endothelial
      cells (HUVEC). MATERIAL AND METHODS: Fresh human umbilical cords were collected
      after a maximum of 6 - 8 h post delivery. They were stored in sterile tubes till
      further preparation. After predilation the umbilical cord veins, a 6 French brush
      catheter was inserted, expanded, and removed by hand using rotating movements.
      The nylon brush was shaken out in cell medium containing serum proteins by a
      connected motor drive. After repeating these procedures, the detached endothelial
      cells were centrifugated and resuspended. The cell numbers were assessed and cell
      viability controlled. RESULTS: The endothelial cell (EC) viability depended on
      the umbilical cord's age and was the highest (29.8 +/- 11.4 %) within 3 h after
      delivery. The brush abrasion (3.32 x 10(5) +/- 52016 viable EC/10 cm vein
      segment) enabled us to culture these cells under different cell concentrations.
      They grew to confluence after 2 - 3 weeks. CONCLUSIONS: The brush-catheter
      abrasion is an effective method for collecting viable human endothelial cells in
      vitro.

PMID- 11588687
TI  - Intracortical osteosarcoma: is MRI useful?

PMID- 11588688
TI  - [Takayasu aortitis with involvement of pulmonary arteries--differential pulmonary
      embolism diagnosis].

PMID- 11588689
TI  - [Tolosa-Hunt syndrome--a differential neuroradiologic diagnosis?].

PMID- 11588690
TI  - Parallel analysis of individual and aggregated data on antibiotic exposure and
      resistance in gram-negative bacilli.
AB  - To evaluate the potential bias of analyzing aggregated data, we separately
      examined antibiotic exposure and resistance data for 35,423 patients admitted to
      a university hospital in Utah, from both an individual-patient perspective and
      group-level perspective. From 1994 through 1998, use of defined daily doses (per
      1000 patient-days) of fluoroquinolones, third-generation cephalosporins,
      ampicillin-sulbactam, and imipenem increased by 82%, 38%, and 99%, and decreased
      by 38%, respectively, whereas group-level resistance rates of Enterobacteriaceae
      or Pseudomonas species changed only minimally. However, in individual-patient
      level analyses performed by multivariable proportional hazards regression,
      exposure to a fluoroquinolone, third-generation cephalosporin, ampicillin
      sulbactam, or imipenem was a strong risk factor for resistance to
      fluoroquinolones (adjusted hazard ratio [AHR], 4.0; P<.001), third-generation
      cephalosporins (AHR, 3.5; P<.001), ampicillin-sulbactam (AHR, 2.3; P=.008), or
      imipenem (AHR, 5.7; P<.001), respectively. Thus, group-level and individual
      patient-level analyses of antibiotic-use-versus-susceptibility relations yielded
      divergent results. Multicenter studies should include individual-patient-level
      data to elucidate more fully the relation between antibiotic exposure and
      resistance.

PMID- 11588691
TI  - Infection with Burkholderia cepacia complex genomovars in patients with cystic
      fibrosis: virulent transmissible strains of genomovar III can replace
      Burkholderia multivorans.
AB  - Infection with Burkholderia cepacia complex in patients with cystic fibrosis (CF)
      results in highly variable clinical outcomes. The purpose of this study was to
      determine if there are genomovar-specific disparities in transmission and disease
      severity. B. cepacia complex was recovered from 62 patients with CF on > or =1
      occasions (genomovar III, 46 patients; genomovar II [B. multivorans], 19
      patients; genomovar IV [B. stabilis], 1 patient; genomovar V [B. vietnamiensis],
      1 patient; and an unclassified B. cepacia complex strain, 1 patient). Patient-to
      patient spread was observed with B. cepacia genomovar III, but not with B.
      multivorans. Genomovar III strains replaced B. multivorans in 6 patients.
      Genomovar III strains were also associated with a poor clinical course and high
      mortality. Infection control practices should be designed with knowledge about B.
      cepacia complex genomovar status; patients infected with transmissible genomovar
      III strains should not be cohorted with patients infected with B. multivorans and
      other B. cepacia genomovars.

PMID- 11588692
TI  - Effective suppression of vancomycin-resistant Enterococcus species in
      asymptomatic gastrointestinal carriers by a novel glycolipodepsipeptide,
      ramoplanin.
AB  - Nosocomial bloodstream infections due to vancomycin-resistant enterococci (VRE)
      are associated with increased morbidity rates, mortality rates, and
      hospitalization costs. Gastrointestinal carriage of VRE is an important risk
      factor for subsequent infections. This 3-arm, phase II, double-blinded,
      randomized, multicenter, placebo-controlled study evaluated the safety and
      efficacy of oral ramoplanin (a novel, nonabsorbed glycolipodepsipeptide) versus
      placebo for suppression of gastrointestinal VRE colonization. Sixty-eight
      patients who were colonized with VRE were enrolled and received 2 daily doses of
      ramoplanin (100 mg or 400 mg) or placebo orally for 7 days. The primary end point
      was the proportion of persons per group from whom VRE were not recovered (VRE
      free) on days 7, 14, and 21 after screening. After treatment, VRE-free status was
      as follows: day 7, none of the 20 patients in the placebo group, and 17 of 21
      (P<.001) and 18 of 20 (P<.001) in the 100-mg and 400-mg ramoplanin groups,
      respectively; on day 14, 2 of 20 patients in the placebo group, and 6 of 21
      (P=.134) and 7 of 17 (P=.028), in the 100-mg and 400-mg ramoplanin groups,
      respectively. By day 21, there were no differences between treatment groups.
      Adverse events were similar for all treatment groups. Ramoplanin was safe and
      effective in temporarily suppressing gastrointestinal VRE carriage.

PMID- 11588693
TI  - Variant effect of first- and second-generation antihistamines as clues to their
      mechanism of action on the sneeze reflex in the common cold.
AB  - Treatment with first-generation antihistamines reduces sneezing, rhinorrhea,
      nasal mucus weight, and, in some instances, cough in subjects with experimental
      or natural colds; however, treatment with second-generation antihistamines has
      not been effective for these complaints in trials in subjects with natural colds.
      This article reports the negative results of a clinical trial with loratadine, a
      second-generation antihistamine, in adults in the rhinovirus challenge model.
      This finding in the highly controlled setting of the challenge model confirms the
      earlier negative studies with second-generation antihistamines in natural colds.
      First-generation antihistamines block both histaminic and muscarinic receptors as
      well as passing the blood-brain barrier. Second-generation antihistamines mainly
      block histaminic receptors and do not pass the blood-brain barrier. The
      effectiveness of first-generation antihistamines in blocking sneezing in colds
      may be due primarily to neuropharmacological manipulation of histaminic and
      muscarinic receptors in the medulla.

PMID- 11588694
TI  - Pneumococcal conjugate vaccine serotypes of Streptococcus pneumoniae isolates and
      the antimicrobial susceptibility of such isolates in children with otitis media.
AB  - The ability of the recently licensed 7-valent pneumococcal conjugate vaccine to
      cover isolates that cause otitis media, especially drug-resistant ones, was
      assessed using 500 recently obtained US isolates. Of these isolates, 418 (84%)
      belonged to vaccine-related serogroups, whereas 82 (16%) belonged to non-vaccine
      related serogroups. Serotype 3 accounted for 48 (59%) of the non-vaccine-related
      serogroups. In addition, 93% of the isolates from patients < or =3 years of age
      belonged to serotypes that were included in or related to the heptavalent
      vaccine, compared with 49% of the isolates from older patients (P=.001). Most of
      the isolates (98%-100%) that were resistant to the antimicrobial agents tested
      were covered by the heptavalent vaccine, including 95.1% of the isolates from
      patients <2 years of age. The 7-valent pneumococcal conjugate vaccine could
      therefore potentially provide protection against all but 1 (type 3) of the common
      otitis media-associated pneumococcal serogroups identified in this study as well
      as against 98% of antibiotic-resistant isolates.

PMID- 11588695
TI  - National shortages of antimicrobial agents: results of 2 surveys from the
      Infectious Diseases Society of America Emerging Infections Network.
AB  - In November 1999 and August 2000, the Infectious Diseases Society of America
      Emerging Infections Network (EIN) surveyed its members about shortages of
      antimicrobial agents in their hospitals and medical centers. Almost 90% of the
      members had encountered shortages of 1 or more agents in 1999. Of 496
      respondents, 382 (77%) reported diminished supplies of penicillin G. Other agents
      in short supply included meropenem (38%), ticarcillin with or without clavulanate
      (24%), cefazolin (20%), gentamicin (50%), and nafcillin-oxacillin (13%). In 2000,
      291 (60%) of 485 respondents reported shortages of penicillin G, but
      significantly fewer members had experienced a lack of other agents. In both
      surveys, members indicated that shortages had affected numerous therapeutic
      indications. In 1999, members estimated that shortages had affected thousands of
      patients. In 2000, they estimated that fewer patients were affected. The results
      of these 2 EIN surveys raise questions about the forces that govern the
      availability of these valuable therapeutic resources.

PMID- 11588696
TI  - Shortages of antibiotics, antivirals, and vaccines threaten the public health.

PMID- 11588697
TI  - Use of real-time PCR on blood samples for diagnosis of invasive aspergillosis.
AB  - We developed a new quantitative system for diagnosis of invasive pulmonary
      aspergillosis (IPA) using real-time automated polymerase chain reaction (PCR).
      Intra-assay and interassay precision rates for in vitro examination were 2.53%
      and 2.20%, respectively, and the linearity of this assay was obtained when there
      were >20 copies/well. We examined 323 samples taken from 122 patients with
      hematological malignancies, including 33 patients with IPA and 89 control
      patients. Blood samples were subjected to PCR antigen detection methods, using
      enzyme-linked immunosorbent assay (ELISA) and determination of plasma (1-->3)
      beta-D-glucan (BDG) concentration. The sensitivities of PCR, ELISA, and BDG
      measurement for diagnosis of IPA were 79%, 58%, and 67%, respectively; the
      specificities were 92%, 97%, and 84%. Positive findings on PCR preceded those of
      computed tomography by -0.3+/-6.6 days, those of BDG measurement by 6.5+/-4.9
      days, and those of ELISA by 2.8+/-4.1 days. Real-time PCR was sensitive for IPA
      diagnosis, and quantitation was accurate.

PMID- 11588698
TI  - A randomized double-blind study of caspofungin versus amphotericin for the
      treatment of candidal esophagitis.
AB  - Caspofungin is a new broad-spectrum antifungal drug. A multicenter, double-blind,
      randomized trial was conducted to assess the efficacy, safety, and tolerability
      of caspofungin relative to amphotericin B in adults with endoscopically
      documented symptomatic Candida esophagitis. By use of a modified intent-to-treat
      analysis, endoscopically verified clinical success was achieved in 74% (95%
      confidence interval [CI], 59%-86%) and 89% (95% CI, 72%-98%) of patients
      receiving caspofungin at 50 and 70 mg/day, respectively, and in 63% (95% CI, 49%
      76%) of patients given amphotericin B at 0.5 mg/kg/day. Therapy was stopped
      because of drug-related adverse events in 24% of patients in the amphotericin B
      group and 4% and 7%, respectively, for the caspofungin groups. This report
      provides the first demonstration of clinical utility for an echinocandin
      compound. Caspofungin appeared in this study to be as effective as and better
      tolerated than amphotericin B for the treatment of esophageal candidiasis.

PMID- 11588699
TI  - Coccidioidomycosis in solid organ transplantation.
AB  - Coccidioidomycosis is an endemic fungal infection of the southwestern United
      States. Normally a self-limited infection in healthy hosts, coccidioidomycosis
      can become a serious complication in patients who have had solid organ
      transplantation. Among patients whose solid organ transplantation was complicated
      by coccidioidomycosis, the infection has a variety of clinical presentations.
      Disseminated disease is common and has substantial morbidity. Patients at risk
      for coccidioidal infection should be identified so that antifungal prophylactic
      therapy can be initiated. Treatment options include amphotericin B or azoles.
      Secondary prophylaxis is recommended because relapse is frequent.

PMID- 11588700
TI  - Travel vaccines and elderly persons: review of vaccines available in the United
      States.
AB  - Aging is associated with alterations in immune responses and may lead to
      clinically significant changes in the safety, immunogenicity, and protective
      efficacy of certain vaccines. This review summarizes published data regarding the
      effects of age on responses after immunization with vaccines generally
      administered before travel. The specific vaccines discussed in detail include
      hepatitis A, typhoid, yellow fever, Japanese encephalitis, and rabies vaccines.
      There is some evidence of diminished serological responses to hepatitis A and
      rabies vaccines in older individuals. In addition, increased toxic effects
      following yellow fever vaccination in elderly recipients have recently been
      reported. However, many travel-related vaccines have never been studied
      specifically in elderly populations. Consideration of potential age-related
      differences in responses to travel vaccines is becoming increasingly important as
      elderly persons more frequently venture to exotic destinations.

PMID- 11588701
TI  - Evolution of coinfection with human immunodeficiency virus and hepatitis C virus
      in patients treated with highly active antiretroviral therapy.
AB  - A retrospective analysis of data from a cohort of patients coinfected with human
      immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were treated with
      highly active antiretroviral therapy (HAART) at 3 infectious diseases units in
      northern Italy was performed. While the patients were receiving HAART, CD4(+)
      cell counts significantly increased and HIV RNA serum levels decreased. However,
      no significant overall changes in alanine aminotransferase (ALT) levels and HCV
      RNA serum levels were observed. Fifteen (4.6%) of 323 patients died within 3
      years of follow-up; death was related to cirrhosis in 5 patients (1.6%). No
      significant difference was observed between cirrhosis-related mortality and
      mortality related to other causes. Patients with ALT levels >4 times the normal
      values at initiation of HAART showed a significant decrease in ALT levels,
      whereas patients with normal ALT levels at initiation of HAART showed a
      significant increase over time, suggesting that HAART may have long-term
      beneficial or detrimental effects, depending on patient characteristics.

PMID- 11588702
TI  - The influence of tumor necrosis factor-alpha and interleukin-10 gene promoter
      polymorphism on the inflammatory response in experimental human endotoxemia.
AB  - In this study, we show that there is no correlation between tumor necrosis factor
      alpha gene promoter polymorphism at position -308, interleukin-10 gene promoter
      polymorphism at position -1082, and the cytokine levels they produce in the human
      endotoxemia model.

PMID- 11588703
TI  - The medical letter's advice for travelers.

PMID- 11588704
TI  - Bergeyella zoohelcum bacteremia after a dog bite.

PMID- 11588705
TI  - Opportunistic parasitic infections of the intestinal tract in the era of highly
      active antiretroviral therapy: is the CD4(+) count so important?

PMID- 11588706
TI  - Desmopressin treatment for a case of dengue hemorrhagic fever/dengue shock
      syndrome.

PMID- 11588707
TI  - Aspiration pneumonia: a misnomer.

PMID- 11588708
TI  - Occurrence of acute hepatitis A in patients infected with human immunodeficiency
      virus.

PMID- 11588709
TI  - Central venous catheter-associated Nocardia bacteremia.

PMID- 11588710
TI  - [Pharmacological treatment with risperidone in children with behavior disorders].
AB  - INTRODUCTION: Behavior disorders are frequently seen in children attending a
      neuropaediatric clinic. The classical neuroleptic drugs are usually used for
      treatment. However response tends to be irregular with adverse effects at a
      cognitive level and extrapyramidal symptoms. PATIENTS AND METHODS: We started to
      use risperidone in children with serious behavior problems who had not responded
      to other drugs, and evaluated the clinical course and side effects. RESULTS: A
      total of 16 patients aged between 7 and 14 years were treated for diagnoses of:
      hyperactivity attention deficit disorder, mental retardation with non specific
      behavior disorder, Gilles de la Tourette disorder with hyperactivity attention
      deficit disorder and generalized disorder of development. The doses of
      risperidone varied between 0.01 and 0.05 mg/kg/day. In two cases the evolution
      could not be assessed, was good in 10 and no change was seen in 4. The group of
      patients with most improvement were those with mental retardation. The commonest
      adverse effect was weight gain. No patient had extrapyramidal symptoms.
      CONCLUSION: We consider risperidone to be a safe drug for the pharmacological
      treatment of children with behavior problems.

PMID- 11588711
TI  - [Medical treatment of pervasive developmental disorders].
AB  - OBJECTIVE: Pervasive developmental disorders, exemplified by autism, constitute
      clinical entities which require the attention of child neurologists. DEVELOPMENT:
      The increasing frequency with which these disorders are diagnosed supports the
      need to review and bring up to date the available data, so as to achieve good
      practice. CONCLUSIONS: There are many studies and initiatives to orient the child
      neurologist as to the steps to be taken regarding aspects such as early
      identification, association with known syndromes, genetic counselling and medical
      advice in general, neuroimaging techniques, treatment of possible associated
      epilepsy and use of psychotropic drugs. All these elements have to be
      incorporated into an overall individualized program which, at the present time,
      has to be basically educational and rehabilitation, so as to attain maximum self
      sufficiency and social participation.

PMID- 11588712
TI  - [Orphan drugs and orphan diseases].
AB  - OBJECTIVES: To define the concepts of orphan drugs and diseases, the current
      situation of clinical investigation of them, the attitude of the pharmaceutical
      industry and aspects of health legislation, especially in the European Community.
      DEVELOPMENT: We review the history of orphan drugs, the name used for those
      drugs, apparatus, biological agents and dietetic preparations used to treat
      diseases so rare as to affect 650 1,000 persons per million inhabitants.
      Approximately 5,000 of such disease have been identified. Of these, 80% are
      genetic disorders which are very common in neuropaediatrics, since 50% appear in
      childhood. Half of these disorders affect the nervous system but in general there
      are no relative preventive and/or therapeutic methods. In view of the expense
      involved, the pharmaceutical industry is loath to develop products which are only
      used in rare diseases. Society cannot tolerate the fact that these patients do
      not have access to medical progress. For this reason organizations of affected
      persons (especially the National Organization for Rare Diseases) put pressure on
      the USA authorities leading to the Orphan Drug Act of 1983 which was subsequently
      copied by other countries. Since January 2000 there is a similar Regulation in
      the European Community. Orphan diseases need to be diagnosed early by specialists
      who have had patients referred to them by general practitioners. However, initial
      recognition of the disorder is often delayed and late diagnosis occurs in 45% of
      these rare diseases which make up 10% of human illnesses. Currently over 150
      orphan drugs are being used for over seven million patients. CONCLUSION: The
      struggle to treat rare diseases must continue, since its true importance is shown
      when suffered personally.

PMID- 11588713
TI  - [Orphan drugs and metabolic disorders].
AB  - INTRODUCTION: Over the past twenty years the legal and philosophical concept of
      orphan diseases has developed to include the diseases with an incidence in the
      general population of less than 1/5,000. Treatment of these conditions, which is
      very specific, requires drugs which will be used by a very small number of
      patients and are therefore not profitable from the financial point of view. This
      gives rise to the concept of orphan drugs which lack sponsorship, are expensive
      to investigate and develop, are little used and therefore there is little
      incentive to market them. All metabolic disorders due to genetic defects may be
      considered to be orphan diseases , since their incidence in the population is
      less than 1/5,000 and there may be only a negligible incidence of 1/37,000,000.
      DEVELOPMENT: In this study we discuss the treatment of three orphan metabolic
      diseases, which severely affect the central nervous system by different
      mechanisms, by three orphan drugs which solve the problems of only a few
      patients. We describe the treatment of: (1) the deficiency of the synthesis of
      tetrahydrobiopterin, which causes neurotransmitter deficiency, with
      tetrahydrobiopterin, (2) N acetylglutamate sythetase deficiency, which causes
      severe hyperammonaemia and cerebral oedema, with N carbamyl glutamate (3)
      cystathionine synthetase deficiency which causes hyperhomocyteinaemia and a high
      risk of thromboembolic accidents, with Betaine.

PMID- 11588714
TI  - [Transplant of hematopoietic stem cells in X-linked adrenoleukodystrophy].
AB  - Over 130 patients with adrenoleukodystrophy have received hematopoietic stem cell
      transplantation from normal donors. Without treatment, this disease has an
      inexorable fatal course. On the other hand, all of the engrafted hosts have had a
      remarkable positive clinical improvement in response to normalization of
      previously deficient enzymatic activity. The specific indications and methods for
      transplantation are also included in this article.

PMID- 11588715
TI  - [Frequency of movement disorders in children].
AB  - We analyze the main clinical characteristics of a series of 800 patients seen by
      us, who had movement disorders which had started during childhood. The results
      are compared with those movement disorders of adult onset reported in the
      literature.

PMID- 11588716
TI  - [Prophylactic treatment of headache].
AB  - INTRODUCTION: Headache continues to be the commonest neurological disorder of
      childhood. There are few studies of prophylactic treatment for headache at this
      age, perhaps because of the difficulty in measuring intensity of pain and
      response to treatment in children. Before headache can be treated
      prophylactically, it is necessary to know its exact site and main trigger
      mechanisms. Therefore, treatment has to be adapted to the individual, bearing in
      mind the age of the patient, frequency of headaches, presence or absence of aura,
      intensity of pain and attitude of the family. Behavior therapy, psychological
      support and relaxation exercises may be necessary to reduce the frequency and
      intensity of the headache. DEVELOPMENT: The first prophylactic treatment for
      chronic headache should be identification of any underlying trigger factor.
      Tension type headache may be a simple somatic reaction to stress. Prophylactic
      drugs should be given according to the frequency of headaches, their duration and
      intensity whenever drug treatment for the acute phase has not eased the pain
      completely. The tricyclic antidepressants are the initial drug of choice for use
      in tension headache. It should be remembered that in children drugs should only
      be used when other measures of pain control have proved useless. In general
      prophylactic treatment of migraine should be started as monotherapy, maintained
      for at least one month (approximately between 3 and 6 months) before gradually
      stopping the drug. The drugs usually used in children are adrenergic beta
      blockers, calcium antagonists, seretoninergenic antagonists, antidepressants, non
      steroid anti inflammatory drugs, and the anti convulsant drugs currently being
      developed.

PMID- 11588717
TI  - [Acute treatment of infantile headache].
AB  - INTRODUCTION: There are few studies in children, as compared with adults, of the
      different therapeutic options which may be useful to treat acute episodes of
      headache. There is a degree of anarchy in the use of analgesics for this common
      problem. DEVELOPMENT: Bearing in mind that headache is usually chronic, generally
      occurring as acute episodes, it is necessary to follow rules based on maximum
      efficacy and a minimum of problems due to side effects or habituation. We suggest
      guidelines for the treatment of episodes of headache, initially with drugs
      commonly used in childhood. The first choice is: ibuprofen, naproxene,
      paracetamol or aspirin. Any of these may be associated with metoclopramide to
      increase the effect and spectrum of treatment. Our second choice is nasal
      sumatryptan.

PMID- 11588718
TI  - [Use of antiepileptic drugs in non epileptic disorders].
AB  - INTRODUCTION: Over the past ten years there have been major advances in
      understanding the neurochemistry of the brain. This has led to better
      understanding of the mode of action of the classical antiepileptic drugs and the
      development of new drugs with better pharmacokinetic and pharmacodynamic
      characteristics. For this reason and also due to their wide mode of action, they
      have begun to be used for other clinical disorders, particularly neuropathic
      pain, in the prophylaxis of migraine, in psychiatric disorders and for
      neuroprotection. DEVELOPMENT: When evaluating the literature, only a few studies
      may be found reporting the clinical efficacy of carbamazepine in the treatment of
      trigeminal neuralgia, of valproate sodium for the prophylaxis of migraine and the
      treatment of bipolar disorders and of gabapentine in the prophylaxis of migraine
      and for the treatment of trigeminal neuralgia. They are considered to be drugs of
      second choice when the more traditional drugs have not been satisfactory.
      CONCLUSION: The new antiepileptic drugs have become an excellent option for the
      treatment of neuropathic pain. However, for both this and other clinical
      indications controlled, double blind studies are necessary to determine the
      efficacy, tolerability and precise indications for these drugs within the
      therapeutic arsenal available for these disorders.

PMID- 11588719
TI  - [Is there a relation between Alzheimer s disease and defects of mitochondrial
      DNA?].
AB  - INTRODUCTION: Various studies have related Alzheimer s disease (AD) with
      mitochrondrial defects. These defects may be structural, biochemical or genetic
      in type. Amongst the genetic defects the rearrangement and particular mutations
      described in mitochondrial DNA (mtDNA) are striking. OBJECTIVE: To study the
      incidence of rearrangement and 4 particular mutations in the mtDNA of patients
      with AD, and determine the possible differences from persons taken as controls.
      PATIENTS AND METHODS: Necropsies of the cerebellum, frontal cortex and
      hippocampus of patients with AD and controls. We also used blood from living
      patients diagnosed as having EA and from controls. The samples were analysed
      using hybrid Southern blot with a mitochondrial probe. Particular mutations
      G3196A, A3397G, A4336G and G5460A/T were also analysed. RESULTS: No differences
      were found between the patients and controls, in either brain tissue or blood on
      analysis using Southern. No association was found between the particular
      mutations analysed and the AD of our samples. CONCLUSIONS: The results obtained
      did not support the hypothesis of involvement of mitochondria in AD. Regarding
      rearrangement and the 4 particular mutations analysed in the mtDNA of our
      samples. However, this does not rule out the possible existence of other
      particular mutations which were not analysed and/or other mitochondrial defects
      which contribute to the development of AD.

PMID- 11588720
TI  - [Intracranial arachnoid cysts. A study of a series of 35 cases].
AB  - INTRODUCTION: Arachnoid cysts are cavities with a content similar to
      cerebrospinal fluid, frequently communicating with the subarachnoid space. They
      make up 1% of the intracranial space occupying lesions, and although typically
      seen in children (13%), they may be undiagnosed until the patient has become
      adult. PATIENTS AND METHODS: We review a series of 35 cases of congenital
      intracranial arachnoid cysts in children, which had been investigated in the
      Neuropaediatric Department during 1987 1999. The patients had had cranial CAT and
      MR, and transcranial echography studies. RESULTS: In 85.7% there was a single
      cyst. The Sylvan fissure and posterior fossa were the commonest sites. The age of
      diagnosis was under 1 year in 54.3% and at birth in 25.7%. There were other
      associated malformations of the central nervous system in 31.4%, with agenesis of
      the corpus callosum in 45.5%. The most frequent clinical features on presentation
      of the condition were macrocephaly (31.4%) and epileptic crises (25.7%). The
      surgical treatment most often used was cystoperitoneal shunt. CONCLUSIONS:
      Congenital arachnoid cysts are caused by alteration in the embryogenesis of the
      central nervous system, and hence their association with other malformations and
      prevalence in children. The most frequent clinical findings were macrocephaly,
      due to the size of the cyst or the associated hydrocephaly, and epileptic
      seizures secondary to cortical irritation caused by pressure. Management of
      symptomatic lesions is surgical. The cystoperitoneal shunt was generally used in
      our series, since this was followed by clinical improvement in most cases.

PMID- 11588721
TI  - [Stroke of cardioembolic origin in Chagas disease].
AB  - INTRODUCTION: American trypanosomiasis, Chagas disease is caused by Trypanosoma
      cruzi. Between 10% and 30% of infected persons develop the chronic form, with
      predominance of the cardiac and gastrointestinal forms. Chagas myocardiopathy
      leads to congestive heart failure, dysrhythmias and thromboembolic phenomena, and
      may cause strokes. PATIENTS AND METHODS: We report two patients, a 57 year old
      woman and a 52 year old man, carriers of the chronic cardiac form of Chagas
      disease, with cardioembolic strokes. In both persons, serology was positive for
      Chagas disease (indirect hemagglutination and indirect immunofluorescence). The
      causes of atherothrombotic stroke were ruled out on carotid and transcranial
      Doppler studies. RESULTS: The woman had previously had an infarct of the left
      middle cerebral artery. She was admitted with a stroke involving the
      vertebrobasilar territory. On Holter studies there was second degree
      atrioventricular block and the electrocardiogram showed severe dilated
      myocardiopathy. On magnetic resonance studies there was an old left
      temporoparietal infarct and recent ischaemia of the pons and cerebral peduncle.
      She was anticoagulated and a pacemaker implanted. The man had a right middle
      cerebral artery infarct. His electrocardiogram showed atrial fibrillation and
      left anterosuperior block. The echocardiogram showed left ventricular dysfunction
      and concentric ventricular hypertrophy. CONCLUSIONS: The chronic cardiac form of
      Chagas disease should be included in the differential diagnosis of stroke of
      cardioembolic origin both in endemic areas and in countries to which persons
      exposed to infection during the early years of life emigrate.

PMID- 11588722
TI  - [A descriptive analysis of 81 patients referred to a neurology clinic for
      syncope].
AB  - INTRODUCTION: Syncope is a frequent medical problem which is disabling,
      potentially serious and difficult to treat. Although patients with syncope are
      often sent to Neurology clinics for investigation we have found no published
      report analysing this. OBJECTIVE: To analyze the aetiology of the cases of
      syncope referred to a Neurology Clinic and also the diagnostic usefulness of the
      investigations requested, particularly those of neuroimaging,
      electroencephalogram (EEG) and vascular studies. PATIENTS AND METHODS: A
      prospective study of the patients referred for syncope to a Neurology Outpatient
      Clinic. The patients were classified into three groups: 1. Epileptic seizure, if
      the clinical history suggested the possibility of a convulsion rather than a
      syncope. 2. Syncope of neurological origin, when the syncope is due to a
      neurological disorder. 3. Non neurological cause of the syncope when the syncope
      was not due to neurological disease. RESULTS: We included 81 patients, who made
      up 4.3% of the patients seen in the Neurology Clinic. Epileptic seizures made up
      10% and the other 90% were due to non neurological causes. There was 0%
      usefulness of neuroimaging investigations and vascular studies. The EEG showed
      epileptiform changes in 9% of the patients, with non neurological syncopes.
      CONCLUSION: In patients with syncope neurological investigations are not very
      useful.

PMID- 11588723
TI  - [Guillain Barre syndrome in an intensive care unit].
AB  - INTRODUCTION AND OBJECTIVE: The Guillain Barre syndrome is an inflammatory
      process of the peripheral nervous system. It is potentially reversible. Nowadays
      it is the commonest cause of acute, generalized, flaccid paralysis in the western
      world. Our objective was to present the clinical and electrophysiological
      characteristics of patients with the Guillain Barre syndrome who required
      admission to an intensive care unit. We therefore report our experience over a
      period of four years with patients with this syndrome who were admitted to the
      intensive care unit and given mechanical ventilation. We analyze the current
      incidence of this syndrome, the proportion of patients requiring admission to the
      intensive care unit and connection to mechanical ventilators due to their muscle
      weakness, and the mortality rates of the major case series published. We analyze
      the electrophysiological findings which indicate worse prognosis. Greater axonal
      involvement is seen in patients with poorer recovery, whilst those who made a
      better recovery had a predominantly demyelinating pattern. We studied certain
      clinical features which implied more severe illness and worse functional recovery
      such as the appearance of signs of autonomic nervous system involvement, rate of
      progression until the maximum affectation occurred and advanced age. Finally, we
      discuss the role of current immunomodulation treatment and the evidence of its
      effectiveness. The Guillain Barre syndrome patients admitted to the intensive
      care unit with the greatest index of long term sequelae are characterized by
      being older, with a higher proportion of neurovegatative disorders and have an
      electrophysiological pattern showing signs of greater axonal degeneration.

PMID- 11588724
TI  - [Tuberculous meningioma en plaque without extracerebral tuberculosis. A case
      report].
AB  - INTRODUCTION: Tuberculosis continues to be an intensly extended disease in under
      developed countries in immunodepressed and immunocompetent persons. In the
      central nervous system tuberculous lesions are the most frequent cause of space
      occupying lesions. CLINICAL CASE: We report the case of a young, immunocompetent
      woman from Guinea, currently living in Spain. Following a seizure, neuro imaging
      showed there to be a right frontal space occupying lesion. The characteristics of
      the MR images obtained were fundamental to the determination of the meningeal
      site of the lesion en plaque and to suggest the aetiology as being an infectious
      inflammatory process, although a meningioma could not be ruled out. The absence
      of signs of extracerebral disease, the localization and distribution of the
      lesion and lack of short term response to medical treatment, which covered the
      different diagnostic possibilities, made it necessary to do a diagnostic
      meningeal biopsy. CONCLUSIONS: MR imaging is a great help in the diagnosis of
      tuberculous lesions of the central nervous system. The differential diagnosis
      between tuberculous pachymeningitis and meningioma, both in the form of plaques,
      is extremely difficult without obtaining a biopsy specimen. The finding of
      epithelioid granulomas with caseous necrosis and/or acid alcohol fast bacilli in
      the biopsy specimen is diagnostic of tuberculosis. A single meningeal lesion
      situated in the cortex but with no associated extracerebral disease causes
      considerable difficulty in diagnosis. Tuberculosis must always be remembered in
      view of the increasing number of immigrants from under developed countries.

PMID- 11588725
TI  - [Acute peritonitis and small bowel diverticula in a patient with mitochondrial
      neurogastrointestinal encephalomyopathy].
AB  - INTRODUCTION: Jejunal and ileal diverticula are acquired lesions that are often
      associated with intestinal motility disturbances like those occurring in
      myopathies and neuropathies with visceral affection. Mitochondrial
      neurogastrointestinal encephalomyopathy is characterized by gastrointestinal
      dysmotility, cachexia, ptosis with external ophthalmoparesis, neuropathy,
      leukoencephalopathy and laboratory evidence of mitochondrial alteration. CLINICAL
      CASE: A female patient that since 9 months age presented digestive symptoms:
      diarrhea, nauseous, vomits, slow digestions and abdominal pain. She had myopia.
      At the age of 20, in a seven months period, she precised urgent abdominal
      surgical intervention in three occasions for acute diffuse peritonitis related to
      jejunal and ileal diverticula. She presented cachexia, mild palpebral ptosis,
      external ophthalmoparesis, hypertrophic major auricular nerves, scoliosis, pes
      cavus, distal weakness and hypoesthesia in extremities, bilateral neurosensorial
      hypoacusia and lactic acidosis. The electroneurographic study was compatible with
      severe chronic demyelinating sensitive motor polyneuropathy. In the cerebral MR
      leukoencephalopathy was detected. In muscular tissue it was seen alteration in
      all fibers type I with numerous lipid vacuoles and an increase of mitochondrial
      number in the form of thick grains and subsarcolemmal mitochondrial bags. There
      was no ragged red fibers nor ultrastructural mitochondrial alterations. There was
      chain respiratory complex III deficiency. CONCLUSIONS: In patients with
      intestinal dysmotility manifestations and jejunal and ileal diverticula
      neuropathies and myopathies with visceral affection must be suspected, among them
      MNGIE syndrome.

PMID- 11588726
TI  - [Behcet's disease with atypical double neurological involvement].
AB  - INTRODUCTION: Neurological involvement in Behcet s disease (BD) occurs in 10 30%
      of the cases and is usually central, with the peripheral nervous system being
      rarely involved. It is also unusual for the disorder to present with neurological
      features at the onset. CLINICAL CASE: A 51 year old man with an undefined history
      of brainstem encephalitis and epileptic seizures. He later developed a cerebellar
      syndrome and relapsing orogenital ulcers, diagnosed as BD with involvement of the
      central nervous system. At the present time the patient complained of marked
      deterioration in gait and progressive difficulty with carrying out everyday tasks
      using his upper limbs. On neurological examination there was paresia of the right
      VI cranial nerve, hyporeflexia of the left half of his body, left hypo esthesia
      (slight for touch and discrimination, but marked for proprioception) and
      dissymmetry of upper and lower left limbs. Complementary investigations showed
      there to be sensory polyneuropathy of the left arm and leg. Both central and
      peripheral nervous system alterations improved on steroid treatment. CONCLUSION:
      The probable onset of BD with central nervous system alterations and subsequent
      appearance of peripheral neuropathy are infrequent findings in BD. The relation
      of both disorders with vasculitis is reinforced by the good response to
      immunosuppressive treatment.

PMID- 11588727
TI  - [Cerebral venous thrombosis and familial prothrombin gene G20210a mutation].
AB  - INTRODUCTION: The prothrombin gene variant G20210A was first described as a risk
      factor for deep vein thrombosis, and recently for cerebral venous thrombosis,
      although reported cases had other concomitant risk factors. CLINICAL CASES: A 33
      years old woman, with no previous vascular nor thrombotic risk factors, was
      admitted with thrombosis of superior longitudinal, lateral and sigmoid right
      sinus. The father had deep venous thrombosis 3 years before. One year later, the
      29 year old sister of the proband, developed massive deep venous thrombosis, when
      she was 8 months pregnant. Laboratory investigations showed elevated
      anticardiolipin antibodies titer in the proband. Prothrombin activity was in the
      normal range in the 3 patients. Prothrombin gene mutation G 20210A was detected
      in the 3 patients. CONCLUSION: As the presence of more than one thrombophilic
      factor (in the reported case, prothrombin G20210A mutation and anticardiolipin
      antibodies) increases the likehood of a thrombotic event, it is useful to screen
      for thrombotic genetic conditions, even when other vascular risks are present,
      and vice versa.

PMID- 11588728
TI  - [Rolandic discharges in childhood epilepsy: magnetoencephalographic diagnosis].
AB  - INTRODUCTION: Whole head magnetoencephalography (MEG) systems facilitate
      simultaneous recording from the entire brain surface and deep structures. Thus
      MEG may be accepted as a clinically feasible method for the evaluation of
      epileptic patients not diagnosed with EEG. CLINICAL CASE: A 11 year old female,
      with tonic generalized seizures since birth. At the present time, seizures
      consist of initial focal signs followed by fear sensation and both eyes and
      cephalic deviation to the right, tonic extension of the superior limbs and
      prolonged apnea. Complementary examinations (EEG, Holter EEG, Video EEG, CT, MRI,
      SPECT) were normal. MEG study was conclusive, diagnosing sharp waves in the
      internal face of the left precentral circunvolution. CONCLUSIONS: MEG study s
      utility in seizures focus localization and pseudo seizures differential diagnosis
      has been demonstrated.

PMID- 11588729
TI  - [Synaptic zinc in the central nervous system].
AB  - Apart from iron, zinc is the most abundant oligoelement in the nervous tissue.
      Although the majority of zinc constitutes a stable fraction that is tightly bound
      to molecules and molecular complexes (structural or metabolic zinc), a small
      proportion (10 15% of cerebral zinc) remains as an ion and it is stored inside
      membranous compartments (ionic vesicular zinc). In neurons, most of this ionic
      zinc can be found inside synaptic vesicles and it is released outside the neuron
      during synaptic transmission: this is the synaptic zinc. In the surroundings of
      the synapse, zinc acts over a variety of neuronal receptors and ionic channels,
      playing a modulatory role that is not yet fully understood. The prolonged
      presence of zinc in the vicinity of the synapse allows its translocation to
      postsynaptic neurons, which lack the  defensive  mechanisms (membrane
      transporters that store zinc into vesicles). In this case, zinc acts as a
      neurotoxic and it can induce neuronal cell death. Neurons and glial cells have
      very efficient, although not well known, cleaning mechanisms that eliminate
      synaptic zinc from the extracellular space; it probably is simultaneous with
      glutamate clearance. It is feasible that dysfunction of these zinc cleaning
      systems could induce compensatory mechanisms (precipitation induced by amyloid
      precursor protein) which in turn could potentiate ethiologic factors of Alzheimer
      s disease.

PMID- 11588730
TI  - [White matter changes and cognitive performance in aging].
AB  - OBJECTIVE: In this paper we review the main magnetic resonance studies to show a
      possible relationship between changes in the white matter of the brain or
      leukoaraiosis, and the neuropsychological profile of elderly persons without
      dementia. DEVELOPMENT: The articles published to date show contradictory data,
      and in nearly half the cases reviewed no clear relationship could be established
      between leukoaraiosis and conduct. However, by using sensitive cognitive tests it
      is possible to detect and association between the presence and degree of change
      in the white matter and decline in frontal function such as speed of processing
      information, visuomotor function, verbal fluency, classification and mental
      sequences. Other cognitive areas such as language, memory or visuospatial,
      visuoconstructive and visuoperceptive functions appear less frequently related to
      the presence or intensity of lesions of the white matter of the brain. From a
      neuropsychological point of view, periventricular localization of the
      leukoaraiosis seems to be more important than subcortical localization.
      CONCLUSIONS: The neuropsychological functions most frequently associated with the
      presence of leukoaraiosis are those dependent on the frontal lobes, and are a
      disconnection favoured by the presence of the white matter of the brain, the most
      probable underlying physiopathological mechanism. Although there is evidence
      showing a genetic effect in the appearance of the white matter of the brain,
      study of the genes associated with cognitive deterioration in normal ageing has
      not given conclusive findings.

PMID- 11588731
TI  - [The surgery of epilepsy].
AB  - INTRODUCTION: At the present time the surgery of epilepsy is a safe, effective
      therapeutic option which should be offered to the patient with drug resistant
      epilepsy at the right moment to prevent the irreversible negative consequences of
      uncontrolled seizures. DEVELOPMENT: All patients with drug resistant epilepsy
      should be surgically assessed. In recent years the concept of surgically
      remediable syndrome has been introduced to refer to conditions in which surgical
      treatment gives excellent results: mesial temporal sclerosis, circumscribed
      neocortical lesions, Sturge Weber syndrome and infantile hemiplegic epilepsy are
      good examples in which prolonged, unnecessary delay of surgery should not occur.
      This type of surgery should be undertaken in centres with suitable trained multi
      disciplinary teams with adequate resources and preestablished guidelines. The
      clinical history, surface electroencephalogram monitoring, directed magnetic
      resonance, functional neuroimaging with SPECT and PET and neuropsychological
      studies are the basis for pre surgical diagnosis. These and other investigations
      should be done following the guidelines of each centre and the complexity of the
      disorder in each case. CONCLUSION: Anteromesial resection of the temporal lobe,
      selective amigdalo hippocampectomy, neocortical resection, hemispherectomy or a
      variation of it, section of the corpus callosum and multiple sub pial transection
      are the most usual surgical techniques since good results are obtained with them
      in suitable cases.

PMID- 11588732
TI  - [Training program in strategies to improve memory].
AB  - INTRODUCTION: The Training Program in Strategies to Improve Memory arises like
      answer to the high percentage of complaints that older people express on their
      loss of memory. The main aim of this program is to intervene in those failures,
      trying to improve the quality of life of this population sector, more and more
      numerous. DEVELOPMENT: The specific objectives of this Program are: to inform on
      what it is, how it works and how it is possible to improve the memory; to learn a
      wide range of useful strategies to obtain it; and to modify attitudes and beliefs
      on the memory of older people. The phases of the Program are: 1. Pre training
      evaluation: a battery of test, that have relation with the tasks and strategies
      that they are going to handle in the training sessions, is administered. 2.
      Training program: it consists of nine sessions of 90 minutes of duration each
      one, with a frequency of two sessions per week. In the sessions they deal with
      attention, concentration, memory, perception, language, etc., through the
      learning of the following strategies: association, categorization, visualization,
      repetition, etc. Each session has its own objectives, tasks and strategies to
      learn. There are 10 or 12 people in each group. 3. Posttraining evaluation: it is
      applied when finalizing the nine sessions of training. The same wide range of
      tests than in the first evaluation is administered (different forms or versions).
      4. Final evaluation: it is made to the six months of the application of the
      training program. It tries to measure if the subjects keep on using the learnt
      strategies. 5. Monitoring sessions: during the six months mentioned, two
      monitoring sessions are carried out to fix the strategies to learnt. 6.
      Evaluation of the program: an evaluation of human and material resources employed
      and activities is made, just like the satisfaction with the program. At the
      present time, this program has been applied to 34 older than sixty people, and
      the results obtained demonstrate the existence of a clear improvement after the
      training, which is maintained six months after. But in addition to the mentioned
      improvement, the data show a reduction in the levels of anxiety and depression.

PMID- 11588733
TI  - [Strategies to follow in the design of neuropsychological rehabilitation programs
      for brain injured people].
AB  - INTRODUCTION: Before initiating the planning of the neuropsychological
      rehabilitation program for a brain injured patient, it is necessary to make and
      comprehensive neuropsychological evaluation. This evaluation has to be oriented,
      not only to the scores obtained, but how cognitive processes are deteriorated. In
      this sense, it is very important to pay attention to the strategies used by the
      subject to carry out each one of the tasks that we present to him, and the
      emotional factors that can influence in the success of the rehabilitation program
      like, for example, awareness of the deficits or familiar and social pressures.
      DEVELOPMENT: The neuropsychological rehabilitation program must take care of
      several fundamental issues: 1. The treatment of the altered cognitive functions
      (cognitive rehabilitation): the use of different principles like the restoration,
      the compensation or the substitution will be determined. 2. The modification of
      the dysadaptative behaviors (irritability, aggressiveness, etc.) by means of
      different operating techniques. 3. The professional readaptation or
      reintegration: one of the final objectives of the rehabilitation is the
      reintegration of the brain injured person in the work or studies that did before
      or in those for which is enabled. 4. The psychosocial support: it is impo0rtant
      to work with the relatives and the social surroundings, specially the paper of
      the associations and the support groups. The design of the rehabilitation program
      must be focused to the specific necessities of each individual patient. It is
      also advisable to combine the individual and group treatment sessions.

PMID- 11588734
TI  - [Outcome after an intensive, holistic and multidisciplinary rehabilitation
      program after traumatic brain injury. Medico legal values].
AB  - INTRODUCTION: This paper was designed to evaluate the integral rehabilitation
      treatments for patients with traumatic brain injury; data about efficiency of the
      C.RE.CER. intensive, holistic and multidisciplinary rehabilitation program is
      given. PATIENTS AND METHODS: The study was done keeping in mind not only the
      clinical aspects of rehabilitation, but also setting it within the judicial realm
      in which a great number of brain injury cases are found, mainly when caused by
      traffic accidents. A sample of 10 severe traumatic brain injury patients was
      studied, aged between 19 and 39. All the patients were assessed at the beginning
      and the end of the treatment, using a neuropsychological test battery, meanwhile
      were treated with the C.RE.CER. intensive, holistic and multidisciplinary
      rehabilitation program. RESULTS AND CONCLUSIONS: The results show a high
      efficiency of treatments in the majority of the patients, with reductions of more
      than 70% in emotional deficits and more than 60% in the global recovery of the
      patients that carried out the programs. This paper also shows some limitations of
      the criteria for compensation in Spanish legislation.

PMID- 11588735
TI  - [Directions in cognitive rehabilitation].
AB  - INTRODUCTION: In spite of the numerous investigations generated for the detection
      of cognitive deficits in diverse populations (head injured, mental diseases),
      there is not an equipable volume of research directed to the study of the
      rehabilitation. However, little by little, it is detected a certain hegemony of
      the techniques used in relation to the subject that sublies of bottom. To take as
      frame the integrating model on the cognition from Parente and Herrmmann (1996),
      in which three types different from variables are considered (active, passive and
      support) serves to fit the different directions in the cognitive rehabilitation.
      DEVELOPMENT: In the present work the cognitive rehabilitation was fitted, each
      one of the approaches would be described (therapy stimulation, training of
      processes, training in strategies, processing with nutrients and medication,
      external aids, increase of the physical and emotional health and social
      functioning, operant conditioning and neural repairing).

PMID- 11588736
TI  - Effects of an exercise program on the rehabilitation of patients with spinal cord
      injury.
AB  - OBJECTIVES: To evaluate the impact of directed physical exercise in patients with
      spinal cord injury (SCI) and to measure functional independence before and after
      an exercise program. DESIGN: Case series. SETTING: Tertiary care center.
      PARTICIPANTS: Thirteen volunteers with thoracic SCI. INTERVENTION: Patients
      participated in a 16-week exercise program, consisting of 3 weekly 120-minute
      sessions. They performed mobility, strength, coordination, aerobic resistance,
      and relaxation activities. MAIN OUTCOME MEASURES: The FIM instrument, arm crank
      exercise test, wheelchair skills, maximum strength, anthropometry (body
      composition measurements), and lipid levels. The results were processed by using
      nonparametric statistical tests. RESULTS: After comparing the values at the
      beginning and end of the program, patients showed a significant increase in the
      following parameters: average FIM score (p < .001) 113 +/- 7.1; weight lifted in
      the bench press exercise (46%, p < .0001), military press (14%, p < .0002), and
      butterfly press exercise (23%, p < .0001), and number of repetitions for biceps
      (10%, p <.0001), triceps (18%, p < .0001), shoulder abductors (61%, p < .0001),
      abdominals (33%, p <.009), and curl back neck exercise (19%, p < .0001). The
      maximum resistance achieved during the arm crank exercise test increased (p <
      .001), and heart rate 6 minutes after the exercise test decreased (p <.05). The
      time required for the wheelchair skill tests significantly decreased in all the
      tasks. No statistically significant changes occurred in body weight (p < .154),
      percentage of body fat (p < .156), lean body weight (p < .158), cholesterol/high
      density lipoprotein cholesterol ratio (p < .076), or maximum heart rate (p <
      .20). The only complication arose in a patient who developed transient sinus
      bradycardia and hypotension after the arm crank exercise test. CONCLUSION: The
      directed exercise program had a positive impact for most of the variables of the
      study.

PMID- 11588737
TI  - Prediction of functional outcomes after traumatic brain injury: a comparison of 2
      measures of duration of unconsciousness.
AB  - OBJECTIVE: To compare the usefulness of time until motor localization occurs
      versus time until commands are followed in predicting outcome after traumatic
      brain injury (TBI). DESIGN: A retrospective analysis of data from a prospective
      cohort study of subjects with severe TBI. SETTING: Seventeen Traumatic Brain
      Injury Model System programs. PARTICIPANTS: A total of 496 subjects, recruited
      through the TBI Model System programs, with loss of consciousness greater than 1
      day, with no late neurosurgical complications, and complete data for all
      measures. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Time until
      Glasgow Coma Scale (GCS) motor score of 5 (time to motor localization) and time
      until GCS motor score of 6 (time until commands were followed) were abstracted
      from medical records. Functional outcomes were assessed at inpatient
      rehabilitation admission and discharge, along with acute and rehabilitation
      lengths of stay and charges. RESULTS: Time until commands were followed was a
      better predictor of all of the outcomes assessed than time until motor
      localization occurred. In multiple regression models, time until motor
      localization did not add significantly to the prediction provided by time until
      commands were followed. The predictive power of time to command following was
      superior even in the subgroup with poor language comprehension as measured by the
      Token Test. CONCLUSION: Despite the theoretical appeal of time to motor
      localization (eg, in persons with language comprehension problems), time to
      command following appears to be a more powerful predictor of outcome after severe
      brain injury.

PMID- 11588738
TI  - Is there a relation between neuropsychologic variables and quality of life after
      stroke?
AB  - OBJECTIVES: To describe the quality of life (QOL) of stroke patients and to
      distill neuropsychologic predictors for poor QOL. DESIGN: A cohort study in which
      patients were neuropsychologically assessed at a mean of 72.2 days after stroke,
      with follow-up at a mean of 9.8 months after stroke. SETTING: Research department
      of a rehabilitation center. PATIENTS: A consecutive sample of 164 stroke patients
      (mean age, 55.2yr) recruited from a university hospital, a regional hospital, and
      a rehabilitation center. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Orientation, memory, attention and concentration, visuospatial and
      visuoconstructive functions, language, and arithmetic skills were assessed with
      neuropsychologic tests. QOL was assessed with the Sickness Impact Profile (SIP).
      RESULTS: An overall mean SIP score +/- standard deviation of 20 +/- 11 showed
      that stroke has a high impact on everyday functioning. Further analyses indicated
      that QOL is related in particular to tests measuring spatiotemporal and/or
      sequential aspects of behavior. Forward/backward stepwise regression analysis (n
      = 106) showed that poor QOL was more likely if patients had a poor result on the
      Trailmaking Test (TMT) B and/or were women. CONCLUSION: The predictive value of
      the TMT is most effective and very useful because the TMT is a short and
      economical procedure. However, the gender-related aspects of recovery deserve
      more attention, as does the possible bias that can be caused by the composition
      of a measurement. Further research is needed to refine predictive models that are
      needed to facilitate the development of more adequate, individual rehabilitation
      programs.

PMID- 11588739
TI  - Characteristics of persons rehospitalized after stroke rehabilitation.
AB  - OBJECTIVE: To develop classification models for risk of hospital readmission 80
      to 180 days after discharge based the demographic and functional characteristics
      of persons discharged from acute inpatient rehabilitation after stroke. DESIGN:
      Retrospective, using information from US facilities subscribing to the Uniform
      Data System for Medical Rehabilitation (UDS(MR)). SETTING: Information submitted
      to the UDS(MR) from 1994 through 1996 by 167 hospital and rehabilitation
      facilities from 40 states was examined. PARTICIPANTS: A total of 15,992 records
      of patients (mean age +/- standard deviation, 70.97 +/- 12.19yr) with a diagnosis
      of stroke were included in the final sample. The sample included 52.7% women and
      was 80% non-Hispanic white with an average length of stay (LOS) of 25.31 +/-
      14.72 days. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Six subscales
      of the FIM instrument (self-care, sphincter control, transfers, locomotion,
      communication, social cognition), total FIM, and other predictor variables for
      regression analysis (gender, age, ethnicity, marital status, prehospital living
      setting, LOS, primary payer source, level of function-related group). RESULTS: A
      logistic regression model included the following statistically significant
      variables (p <.05): ethnicity, sphincter control, self-care ability, gender, and
      LOS. The greatest variability occurred among men. Exactly 18.1% of non-Hispanic
      white men and 17.9% of African-American men were rehospitalized. In contrast,
      only 10.1% of Hispanic men and 11.4% of Asian men were rehospitalized. The odds
      of rehospitalization were lowest for Hispanic men. CONCLUSION: As prospective
      payment systems are introduced for postacute care, it is important that the
      relationship among functional abilities, demographic characteristics, and
      incidence of hospital readmission following medical rehabilitation be examined.

PMID- 11588740
TI  - Comparing stroke rehabilitation outcomes between acute inpatient and nonintense
      home settings.
AB  - OBJECTIVE: To compare outcomes in stroke survivors who received rehabilitation
      services in an acute inpatient rehabilitation setting (multidisciplinary
      rehabilitation team) with outcomes in survivors in a home-based setting (family
      caregivers, limited team supervision). DESIGN: Randomized clinical trial, with
      mean follow-up after 60 days. SETTING: Inpatient rehabilitation setting and home
      based settings. PATIENTS: Sixty patients (age range, 43-80yr) who had a stroke
      between 1996 and 1999 and had been referred after medical stabilization, randomly
      divided into 2 groups: group 1, inpatient rehabilitation; group 2, home-based
      rehabilitation. INTERVENTIONS: Group 1: therapeutical and neuromuscular exercises
      with occupational therapy with professional supervision; group 2: conventional
      exercises with family caregiver and limited professional supervision. MAIN
      OUTCOME MEASURES: Spasticity was evaluated with the Ashworth Scale, motor status
      with Brunnstrom's stages, functional status with the FIM instrument, and
      cognitive status with the Mini-Mental State Examination before and after
      rehabilitation. RESULTS: Patients rehabilitated in acute inpatient settings had
      better motor, functional, and cognitive outcomes (p < .05). Spasticity changes
      did not differ between the groups. CONCLUSION: Intense inpatient rehabilitation
      services for stroke survivors provide significantly more favorable functional and
      cognitive outcomes with relatively low complications than did nonintense
      rehabilitation efforts in home settings.

PMID- 11588741
TI  - Efficacy of an implanted neuroprosthesis for restoring hand grasp in tetraplegia:
      a multicenter study.
AB  - OBJECTIVE: To evaluate an implanted neuroprosthesis that allows tetraplegic users
      to control grasp and release in 1 hand. DESIGN: Multicenter cohort trial with at
      least 3 years of follow-up. Function for each participant was compared before and
      after implantation, and with and without the neuroprosthesis activated. SETTING:
      Tertiary spinal cord injury (SCI) care centers, 8 in the United States, 1 in the
      United Kingdom, and 1 in Australia. PARTICIPANTS: Fifty-one tetraplegic adults
      with C5 or C6 SCIs. INTERVENTION: An implanted neuroprosthetic system, in which
      electric stimulation of the grasping muscles of 1 arm are controlled by using
      contralateral shoulder movements, and concurrent tendon transfer surgery.
      Assessed participants' ability to grasp, move, and release standardized objects;
      degree of assistance required to perform activities of daily living (ADLs),
      device usage; and user satisfaction. MAIN OUTCOME MEASURES: Pinch force; grasp
      and release tests; ADL abilities test and ADL assessment test; and user
      satisfaction survey. RESULTS: Pinch force was significantly greater with the
      neuroprosthesis in all available 50 participants, and grasp-release abilities
      were improved in 49. All tested participants (49/49) were more independent in
      performing ADLs with the neuroprosthesis than they were without it. Home use of
      the device for regular function and exercise was reported by over 90% of the
      participants, and satisfaction with the neuroprosthesis was high. CONCLUSIONS:
      The grasping ability provided by the neuroprosthesis is substantial and lasting.
      The neuroprosthesis is safe, well accepted by users, and offers improved
      independence for a population without comparable alternatives.

PMID- 11588742
TI  - Car-driving abilities of people with tetraplegia.
AB  - OBJECTIVES: To examine the relationship between the spinal cord injury (SCI)
      level, age, and car-driving ability in people with tetraplegia and to explore the
      association between car-driving ability and social activity. DESIGN:
      Retrospective clinical survey. SETTING: Rehabilitation center in Japan. PATIENTS:
      Sixty-two subjects with traumatic complete tetraplegia. INTERVENTIONS: Driving
      evaluation; comprehensive driver's training (muscle strengthening, transfer
      training, adjustment of equipment, on-road training); and questionnaire (car
      driving status, employment, participation in sports). MAIN OUTCOME MEASURES: The
      SCI level (Zancolli's classification), age, functional status of activities of
      daily living (ADLs), and driving ability were obtained from the medical records.
      Vocational status and engagement in sports activities were investigated by
      questionnaire. RESULTS: The SCI level and age strongly influenced the patients'
      ability to drive a car independently. The highest neurologic level in which
      independent driving was achievable was C6A. Toilet transfer ability almost
      paralleled the ability to drive a car. Eighty-four percent of the people with
      tetraplegia who had a defined job could drive independently and 70% of the
      driving-independent individuals held a job. Half of driving-independent
      individuals participated in some sports activities. CONCLUSIONS: Toilet transfer
      ability is a reliable indicator for driver's training. Driving ability is an
      important factor that allows individuals with tetraplegia to participate in work
      and sports-related activities.

PMID- 11588743
TI  - The effect of seat tilting on pelvic position, balance control, and compensatory
      postural muscle use in paraplegic subjects.
AB  - OBJECTIVE: To study the effect of seat tilting on pelvic tilt, balance control,
      and postural muscle use in persons with a thoracic spinal cord injury (SCI).
      DESIGN: Cross-sectional group study. SETTING: Rehabilitation centers and
      rehabilitation hospital departments. PATIENTS: Ten complete high thoracic SCI
      (level T2-8) patients, 10 complete low thoracic SCI (level T9-12) patients, and
      10 matched able-bodied controls. INTERVENTION: A 10 degrees forward inclination
      of the seat. MAIN OUTCOME MEASURES: Pelvic tilt, center of pressure displacement,
      and muscle activity. RESULTS: Anterior tilting of the pelvis as a result of
      forward inclination of the seat could not be shown, either in persons with or
      without SCI. Balance control was not influenced by forward inclination of the
      seat. Participants' overall muscle activity decreased while they were seated in
      the chair with the forwardly inclined seat. CONCLUSIONS: Evidence provided by the
      kinematic and electromyographic data is not sufficient to develop a protocol for
      wheelchair prescription on the basis of pelvic positioning.

PMID- 11588744
TI  - Sleep disorders associated with traumatic brain injury.
AB  - OBJECTIVES: To investigate the frequency of sleep disorders in traumatic brain
      injury (TBI) patients with hypersomnia and to discern the relationship between
      posttraumatic sleep disorders and pretraumatic sleep symptoms. DESIGN:
      Prospective cohort study using the criterion standard to diagnose sleep disorders
      in a consecutive sample of TBI patients. SETTING: Academic medical center with
      level I trauma center, rehabilitative medicine services, and accredited sleep
      disorders center. PATIENTS: Ten TBI patients with subjective excessive
      sleepiness. INTERVENTION: Nocturnal polysomnography followed by Multiple Sleep
      Latency Test. Subjects who had overt sleep apnea on the first nocturnal
      polysomnography had a second nocturnal polysomnography with titration of nasal
      continuous positive airway pressure. MAIN OUTCOME MEASURES: Diagnosis of sleep
      disordered breathing, narcolepsy, and posttraumatic hypersomnia. RESULTS: A
      diagnosis of treatable sleep disorder was made in all 10 subjects. Sleep
      disordered breathing was found in 7 subjects: overt obstructive sleep apnea (OSA)
      was diagnosed in 5 subjects, rapid eye movement-related OSA in 1, and upper
      airway resistance syndrome (UARS) in 1. Narcolepsy was diagnosed in 2 subjects,
      and the diagnosis of posttraumatic hypersomnia was made in 1 subject. Three
      subjects had symptoms of hypersomnia before their injury (1 each with narcolepsy,
      OSA, UARS), and 2 of these were driving a car at the time of injury. CONCLUSION:
      Treatable sleep disorders appear to be common in the sleepy TBI population, but
      may be largely undiagnosed and untreated.

PMID- 11588745
TI  - Urinary incontinence in stroke patients after admission to a postacute inpatient
      rehabilitation program.
AB  - OBJECTIVE: To determine the incidence of poststroke urinary incontinence in
      stroke patients admitted for a postacute inpatient rehabilitation program and its
      association with discharge destination. DESIGN: Cohort study of first-time stroke
      patients admitted for a postacute inpatient rehabilitation program from August
      1994 to August 1997. SETTING: Rehabilitation center in the Netherlands.
      PARTICIPANTS: Consecutive first-time stroke patients (n = 143). INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Incidence rates calculated with
      observation time at risk in the denominator. Measures for outcome include the
      Modified Barthel Index (MBI) and the discharge destination. RESULTS: The
      incidence rate of urinary incontinence was 29/1000 persons per month (95%
      confidence interval [CI], 18-48/1000 persons monthly). For incontinent patients,
      the mean initial MBI score +/- standard deviation was 6.0 +/- 2.3 (range, 2-12);
      for continent patients, it was 11.5 +/- 9.8 (range, 2-18). This difference was
      statistically significant (t(139) = 2.12; p = .036; 95% CI for difference of the
      means, .379-10.84). Patients continent at time of discharge were more often
      discharged to their own homes than were incontinent patients (Fisher's exact
      test, p = .0006). CONCLUSIONS: In this select cohort, the incidence of urinary
      incontinence was lower than that reported in the literature. An association was
      found between urinary incontinence and discharge destination and between urinary
      incontinence and functional ability on admission.

PMID- 11588746
TI  - Use of percutaneous gastrojejunostomy feeding tubes in the rehabilitation of
      stroke patients.
AB  - OBJECTIVE: To determine the characteristics of and complications in the
      rehabilitation of stroke patients in whom percutaneous gastrojejunostomy (PGJ)
      feeding tubes have been placed. DESIGN: Retrospective cohort study. SETTING: A
      rehabilitation unit in a tertiary care hospital. PARTICIPANTS: Stroke patients (n
      = 563) admitted to a tertiary care hospital over a 10-year period. INTERVENTION:
      PGJ feeding tubes. MAIN OUTCOME MEASURES: Evidence of aspiration in all
      videofluoroscopic modified barium swallow (VMBS) studies was noted. For patients
      with a PGJ feeding tube, the following were recorded: stroke location; results of
      subsequent VMBS reports; length of time from stroke onset to PGJ feeding tube
      insertion; total time the PGJ feeding tube remained in situ; discharge
      disposition; and concurrent feeding status. Follow-up was at 1-year poststroke.
      Complications during the inpatient stay attributable to the PGJ feeding tube were
      recorded. RESULTS: Thirty-two of all 563 (5.7%) stroke patients admitted and 28
      of the 115 (24.3%) proven aspirators, as shown on VMBS studies, had a PGJ feeding
      tube inserted. Twenty-one of the 563 (3.7%) stroke patients were discharged to
      the community with PGJ feeding tubes in place. The tubes were inserted on average
      37 days after stroke onset. Seventeen of all 88 (19.3%) brainstem stroke patients
      and 15 of all 29 (51.7%) brainstem stroke patients with documented aspiration had
      feeding tubes inserted, whereas only 15 of 475 (3.2%) hemispheric stroke
      rehabilitation patients received a tube. Eleven of 32 (34.3%) patients with a
      feeding tube were able to resume oral feedings at discharge; within 1 year of
      discharge, 24 of 32 (75%) had done so. Although there were no serious
      complications resulting from tube insertions, minor complications were documented
      in more than 50% of the cases. The tubes were associated with prolonged
      institutionalization in only 1 case; most patients were discharged on a home tube
      feeding program. CONCLUSIONS: PGJ feeding tubes were placed in approximately 1 of
      every 20 of our stroke rehabilitation patients. One third of the tubes were
      removed before the patients were discharged from rehabilitation and 75% were
      removed within 1 year. Insertion of the tubes was most common in patients with
      evidence of aspiration and in patients with brainstem strokes. Complications
      caused by the tube were minor and all patients but 1 who were discharged with
      feeding tubes were able to manage the home tube-feeding program.

PMID- 11588747
TI  - Assessing the spastic condition of individuals with upper motoneuron involvement:
      validity of the myotonometer.
AB  - OBJECTIVES: To examine the validity of a newly developed tissue compliance device
      to measure muscle tone and to quantify the level of severity of the spastic
      condition. DESIGN: Validity study. SETTING: Research laboratory. PARTICIPANTS:
      Twenty subjects, 10 with upper motoneuron (UMN) disorders (spastic-type cerebral
      palsy or adult-onset cerebrovascular accident) who comprised the experimental
      group; and 10 nondisabled, age-equivalent subjects, who served as controls.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Muscle tone of the biceps
      brachii muscle was assessed with the Myotonometer and Modified Ashworth Scale
      (MAS). The Myotonometer was used to quantify the muscle's resistance to stretch
      in a relaxed state and during maximal voluntary isometric contractions. Analyses
      of variance determined differences among subjects. Correlations between
      Myotonometer measurements and MAS scores were calculated. RESULTS: Significant
      differences (p < .05) were observed between experimental and control groups and
      between the involved and uninvolved extremities of the experimental group with
      Myotonometer measurements. Correlations between MAS scores and Myotonometer
      measurements ranged from .64 to .81. CONCLUSION: The Myotonometer effectively
      identified differences in the spastic condition of the biceps brachii muscle in
      subjects with UMN involvement. Correlations with the MAS were moderate to high.

PMID- 11588748
TI  - Reproducibility of exercise tolerance in patients with end-stage renal disease.
AB  - OBJECTIVE: To determine the interday reproducibility of peak and submaximal
      exercise tolerance of patients with end-stage renal disease (ESRD). DESIGN:
      Repeated measures. SETTING: Day-patient rehabilitation center. PARTICIPANTS:
      Twelve consecutively presenting, self-selected patients with ESRD. INTERVENTIONS:
      All patients performed peak exercise tolerance assessments on a cycle ergometer
      up to the point of volitional fatigue, with a 1-week interval between the 2
      tests. MAIN OUTCOME MEASURES: Cardiopulmonary, hemodynamic, and physical
      performance parameters were assessed at peak exercise and at the lactate
      threshold. Standard error of measurement, percentage coefficient of variation
      (CV%), intraclass correlation coefficient (ICC), and limits of agreement (LOA)
      were calculated to determine the reproducibility of all variables. RESULTS: CV%
      (range, 5%-7%) and ICCs (range, .94 - .98) for oxygen uptake and heart rate at
      peak exercise and lactate threshold indicated highly acceptable levels of group
      mean reproducibility. LOA analysis revealed satisfactory levels of
      reproducibility for individual patients. CONCLUSION: Taken together, these
      reproducibility data may be applied to clinical work, requiring the
      quantification of changes in the exercise tolerance of patients with ESRD after
      short-term interventions (eg, exercise training, therapeutic use of recombinant
      erythropoietin).

PMID- 11588749
TI  - Factors related to successful job reintegration of people with a lower limb
      amputation.
AB  - OBJECTIVE: To study demographically, amputation-, and employment-related factors
      that show a relationship to successful job reintegration of patients after lower
      limb amputation. DESIGN: Cross-sectional study. SETTING: University hospital.
      PATIENTS: Subjects had an acquired unilateral major amputation of the lower limb
      at least 2 years before, were aged 18 to 60 years (mean, 46yr), and were living
      in the Netherlands. All 322 patients were working at the time of amputation and
      were recruited from orthopedic workshops. INTERVENTION: Questionnaires sent to
      subjects to self-report (1) demographic and amputation information and (2) job
      characteristics and readjustment postamputation. Questionnaire sent to
      rehabilitation specialists to assess physical work load. MAIN OUTCOME MEASURES:
      Demographically related (age, gender); amputation-related (comorbidity; reason
      and level; problems with stump, pain, prosthesis use and problems, mobility,
      rehabilitation); and employment-related (education, physical workload)
      information about the success of job reintegration. RESULTS: Job reintegration
      was successful in 79% and unsuccessful in 21% of the amputees. Age at the time of
      amputation, wearing comfort of the prosthesis, and education level were
      significant indicators of successful job reintegration. Subjects with physically
      demanding jobs who changed type of job before and after the amputation more often
      successfully returned to work than subjects who tried to stay at the same type of
      job. CONCLUSIONS: Older patients with a low education level and problems with the
      wearing comfort of the prosthesis are a population at risk who require special
      attention during the rehabilitation process in order to return to work. Lowering
      the physical workload by changing to another type of work enhances the chance of
      successful reintegration.

PMID- 11588750
TI  - Lower extremity prosthetic mobility: a comparison of 3 self-report scales.
AB  - OBJECTIVE: To assess and compare the reliability and validity of the Houghton
      Scale, the Prosthetic Profile of the Amputee Locomotor Capabilities Index (PPA
      LCI), and the Prosthetic Evaluation Questionnaire (PEQ) mobility subscale, 3
      disease-specific self-report measures of functional mobility for lower extremity
      prosthetic mobility. DESIGN: Four-week test-retest: 1 sample for reliability
      analyses, 1 sample for validity analyses. SETTING: University-affiliated
      outpatient amputee clinic, in Ontario, Canada. PARTICIPANTS: Two outpatient
      amputee samples (sample 1 [n = 55], for reliability analysis; sample 2 [n = 329],
      for validity analysis). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Test-retest of reliability and convergent validity of the 3 scales. Convergent
      validity and discriminative ability were also assessed after setting a priori
      hypotheses for 2 scales of walking performance, balance confidence, and other
      indicators of ambulatory ability. RESULTS: The reliability of the PPA-LCI
      (intraclass correlation coefficient [ICC] = .88) was slightly higher than the
      Houghton Scale (ICC = .85) and the PEQ mobility subscale (ICC = .77). The PPA-LCI
      was prone to high ceiling effects (40%) that would limit its ability to detect
      improvement. Evidence for convergent validity, when compared with the 2-Minute
      Walk Test, Timed Up and Go, and the Activity-Specific Balance Confidence Scale,
      was supported as hypothesized in all the scales. Each of the scales was able to
      discriminate between different groups for amputation cause, walking distance,
      mobility device use, and automatism, with each having varying strength related to
      relative precision. The Houghton Scale was the only scale able to distinguish
      between amputation levels. CONCLUSIONS: Reliability and validity of all the
      scales are acceptable for group level comparison. None of the scales had clearly
      superior psychometric properties compared with the others. Further research is
      required to assess responsiveness.

PMID- 11588751
TI  - Vastus medialis obliquus and vastus lateralis activity in open and closed kinetic
      chain exercises in patients with patellofemoral pain syndrome: an
      electromyographic study.
AB  - OBJECTIVES: To evaluate the electromyographic activities of vastus medialis
      obliquus (VMO) and vastus lateralis (VL) muscles in open and closed kinetic chain
      exercises in subjects with patellofemoral pain syndrome (PFPS). DESIGN: Case
      controlled study. SETTING: Rehabilitation science center in a tertiary medical
      center. PARTICIPANTS: Ten patients with bilateral knee pain diagnosed with PFPS
      and 10 healthy volunteers. INTERVENTIONS: Subjects performed open kinetic chain
      exercise on an isokinetic dynamometer and closed kinetic chain exercise by squat
      to-stand and stand-to-squat tasks. Surface electromyography was done for the VMO
      and VL muscles. MAIN OUTCOME MEASURES: VMO/VL ratios were calculated after
      normalization of muscle activities. RESULTS: The VMO/VL ratios of PFPS subjects
      were significantly lower than were those of unimpaired subjects during knee
      isokinetic closed kinetic chain exercises (p = .047). However, there was no
      statistical difference in VMO/VL ratio between subjects with and without PFPS
      during closed kinetic chain exercises (p = .623). Maximum VMO/VL ratio was
      obtained at 60 degrees knee flexion in closed kinetic chain exercise. CONCLUSION:
      In closed kinetic chain exercises, more selective VMO activation can be obtained
      at 60 degrees knee flexion. Maximal VMO/VL ratio was observed at this knee
      flexion angle, and muscle contraction intensity was also greatest.

PMID- 11588752
TI  - Neuromuscular function during therapeutic knee exercise under water and on dry
      land.
AB  - OBJECTIVES: To compare muscle activity and resistive drag force during knee
      extension-flexion exercises while barefoot and while wearing a Hydro Boot
      (increased frontal area) both under water and on dry land. DESIGN: Participants
      performed the exercises while seated on an elevator chair under water. SETTING: A
      hydrotherapy pool. PARTICIPANTS: Eighteen healthy persons (10 women, 8 men).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Isokinetic and isometric
      forces were measured with a dynamometer. The electromyographic activity of the
      quadriceps (vastus medialis, vastus lateralis) and hamstring muscles (biceps
      femoris) was recorded. The underwater drag for the range of motion was calculated
      by using the general fluid equation. RESULTS: The underwater electromyographic
      patterns showed an early decrease in the concentric activity of the agonists with
      coincidental activation of the antagonists. In addition, the electromyographic
      amplitudes were similar between the 2 underwater conditions, but the Hydro Boot
      produced a higher level (p < .001) of drag than did the barefoot condition. As
      expected, in most cases the forces on dry land were higher (p < .001) than
      underwater drag. In flexion, however, the peak drag with Hydro Boot and
      isokinetic force did not differ. CONCLUSIONS: Increasing the frontal area of the
      lower leg with a Hydro Boot significantly increased the level of water
      resistance, thus, providing flexion forces that approach those measured on dry
      land. This type of water training offers stimulation to enhance the functional
      capacity and performance of the neuromuscular system. In addition, hydrodynamic
      principles and forces that influence the exercising limb must be considered to
      ensure appropriate progression.

PMID- 11588753
TI  - Two configurations of static magnetic fields for treating rheumatoid arthritis of
      the knee: a double-blind clinical trial.
AB  - OBJECTIVE: To assess the efficacy of a nonpharmacologic, noninvasive static
      magnetic device as adjunctive therapy for knee pain in patients with rheumatoid
      arthritis (RA). DESIGN: Randomized, double-blind, controlled, multisite clinical
      trial. SETTING: An American and a Japanese academic medical center as well as 4
      community rheumatology and orthopedics practices. PATIENTS: Cohort of 64 patients
      over age 18 years with rheumatoid arthritis and persistent knee pain, rated
      greater than 40/100mm, despite appropriate use of medications. INTERVENTION: Four
      blinded MagnaBloc (with 4 steep field gradients) or control devices (with 1 steep
      field gradient) were taped to a knee of each subject for 1 week. MAIN OUTCOME
      MEASURES: The American College of Rheumatology recommended core set of disease
      activity measures for RA clinical trials and subjects' assessment of treatment
      outcome. RESULTS: Subjects randomly assigned to the MagnaBloc (n = 38) and
      control treatment groups (n = 26) reported baseline pain levels of 63/100mm and
      61/100mm, respectively. A greater reduction in reported pain in the MagnaBloc
      group was sustained through the 1-week follow-up (40.4% vs 25.9%) and
      corroborated by twice daily pain diary results (p < .0001 for each vs baseline).
      However, comparison between the 2 groups demonstrated a statistically
      insignificant difference (p < .23). Subjects in the MagnaBloc group reported an
      average decrease in their global assessment of disease activity of 33% over 1
      week, as compared with a 2% decline in the control group (p < .01). After 1 week,
      68% of the MagnaBloc treatment group reported feeling better or much better,
      compared with 27% of the control group, and 29% and 65%, respectively, reported
      feeling the same as before treatment (p < .01). CONCLUSIONS: Both devices
      demonstrated statistically significant pain reduction in comparison to baseline,
      with concordance across multiple indices. However, a significant difference was
      not observed between the 2 treatment groups (p < .23). In future studies, the
      MagnaBloc treatment should be compared with a nonmagnetic placebo treatment to
      characterize further its therapeutic potential for treating RA. This study did
      elucidate methods for conducting clinical trials with magnetic devices.

PMID- 11588754
TI  - Current concepts: diffuse axonal injury-associated traumatic brain injury.
AB  - OBJECTIVES: To review the probable physical, physiologic mechanisms that result
      in the medical and neuropsychologic complications of diffuse axonal injury (DAI)
      associated traumatic brain injury (TBI). DATA SOURCES: Various materials were
      accessed: MEDLINE, textbooks, scientific presentations, and current ongoing
      research that has been recently reported. STUDY SELECTION: Included were
      scientific studies involving TBI, particularly direct injury to the axons and
      glia of the central nervous system (CNS) in both in vitro and in vivo models.
      These studies include pathologic findings in humans as well as the medical
      complications and behavioral outcomes of DAI. Studies that addressed animal
      models of DAI as well as cellular and/or tissue models of neuronal injury were
      emphasized. The review also covered work on the physical properties of materials
      involved in the transmission of energy associated with prolonged acceleration
      deceleration injuries. DATA EXTRACTION: Studies were selected with regard to
      those that addressed the mechanism of TBI associated with DAI and direct injury
      to the axon within the CNS. The material was generally the emphasis of the
      article and was extracted by multiple observers. Studies that correlate the above
      findings with the clinical picture of DAI were included. DATA SYNTHESIS: Concepts
      were developed by the authors based on the current scientific findings and
      theories of DAI. The synthesis of these concepts involves expertise in physical
      science, basic science concepts of cellular injury to the CNS, acute medical
      indicators of DAI, neuropsychologic indicators of DAI, and rehabilitation
      outcomes from TBI. CONCLUSIONS: The term DAI is a misnomer. It is not a diffuse
      injury to the whole brain, rather it is predominant in discrete regions of the
      brain following high-speed, long-duration deceleration injuries. DAI is a
      consistent feature of TBI from transportation-related injuries as well as some
      sports injuries. The pathology of DAI in humans is characterized histologically
      by widespread damage to the axons of the brainstem, parasagittal white matter of
      the cerebral cortex, corpus callosum, and the gray-white matter junctions of the
      cerebral cortex. Computed tomography and magnetic resonance imaging scans taken
      initially after injury are often normal. The deformation of the brain due to
      plastic flow of the neural structures associated with DAI explains the
      micropathologic findings, radiologic findings, and medical and neuropsychologic
      complications from this type of injury mechanism. There is evidence that the
      types of cellular injury in TBI (DAI, anoxic, contusion, hemorrhagic, perfusion
      reperfusion) should be differentiated, as all may involve different receptors and
      biochemical pathways that impact recovery. These differing mechanisms of cellular
      injury involving specific biochemical pathways and locations of injury may, in
      part, explain the lack of success in drug trials to ameliorate TBI.

PMID- 11588755
TI  - Atypical hip pain origin in a young athletic woman: a case report of giant cell
      carcinoma.
AB  - Primary bone tumors are infrequently encountered in a sports medicine practice.
      We describe a case in which a young athletic woman with a medical history
      significant for ulcerative colitis initially presented to our clinic with chronic
      hip pain. Her initial roentograms were negative for boney pathology and her
      history and examination were consistent with trochanteric bursitis. However,
      follow-up radiographs performed 9 months later showed a radiolucent mass that
      eventually, after open biopsy and histologic evaluation, was determined to be
      giant cell tumor. This case shows the importance of repeat radiographic studies
      in patients whose joint pain does not respond or responds slowly to conservative
      therapy, despite initial normal findings. It also establishes that radiographic
      findings do not always correlate with actual disease process, for this lesion was
      found to be giant cell carcinoma--a diagnosis contrary to the original diagnosis
      of clear cell chondrosarcoma that was suggested by radiology.

PMID- 11588756
TI  - Neuromuscular electric stimulation in heart transplantation candidates with
      cardiac pacemakers.
AB  - Twenty percent of heart transplantation candidates have cardiac pacemakers.
      Application of neuromuscular electric stimulation (NMES) in patients with
      pacemakers is controversial because of potential electromagnetic field
      interference and subsequent failure of the pacemaker. We present a safety
      protocol as a procedure before applying NMES in pacemaker patients. In 4 patients
      with chronic heart failure, NMES was applied under supervised conditions for 20
      minutes to evaluate the individual risk. No changes in the clinical state and no
      complications secondary to electromagnetic field interference were observed. A
      check of pacemaker function after this 20-minute stimulation revealed no changes
      in the pacemaker parameters. After a thorough safety protocol, NMES of knee
      extensor muscles in patients with pacemakers appears to be safe.

PMID- 11588757
TI  - The 2-minute walk test as a measure of functional improvement in persons with
      lower limb amputation.
AB  - OBJECTIVE: To determine the construct validity and responsiveness of the 2-minute
      walk test as a measure of function in individuals with lower extremity
      amputation. DESIGN: The distances walked in 2 minutes were compared with the
      results on the physical functioning subscale of the Medical Outcomes Study Short
      Form 36-Item Health Survey (SF-36) and the Houghton Scale. SETTING: Regional
      amputee rehabilitation program. PATIENTS: Retrospective data from 290 patients
      (mean age, 66yr) with unilateral transtibial, unilateral transfemoral, or
      bilateral amputations. INTERVENTION: Repeated testing. MAIN OUTCOME MEASURES:
      Distance walked in 2 minutes, SF-36 (aggregated into physical and mental
      composite scores), and the Houghton score. We also examined the change in the
      distance before and after a rehabilitation program. RESULTS: The distance walked
      in 2 minutes showed a weak correlation with the physical functioning subscale of
      the SF-36 (r = .22, p = .008) and a moderate correlation with the total Houghton
      score at discharge from rehabilitation (r = .493, p <or= .001). The correlation
      between distance walked in 2 minutes and SF-36 physical functioning subscale at
      follow-up was moderate (r = .479, p < .001). There was a significant improvement
      in distance walked in 2 minutes at discharge and follow-up compared with baseline
      (mean change +/- standard deviation at discharge, 13.6 +/- 19.9m; at follow-up,
      41.2 +/- 34m, p < .001). CONCLUSION: The 2-minute walk test was responsive to
      change with rehabilitation in persons with lower extremity amputation. In
      addition, the 2-minute walk test showed adequate correlation with measures of
      physical functioning and prosthetic use in this population.

PMID- 11588758
TI  - Comparison of fatigue life for 3 types of manual wheelchairs.
AB  - OBJECTIVES: To examine 3 types of manual wheelchairs-ultralight wheelchairs
      (UWs), lightweight wheelchairs (LWs), and depot wheelchairs (DWs)-and to compare
      the fatigue life between the wheelchair types. DESIGN: A database of different
      manual wheelchairs tested according to the International Organization for
      Standardization (ISO). Fatigue life was determined by using standards that define
      methods accepted internationally using double-drum and curb-drop testing
      equipment. SETTING: A rehabilitation engineering center. SPECIMENS: Sixty-one
      manual wheelchairs: 25 DWs, 22 UWs, and 14 LWs. MAIN OUTCOME MEASURES:
      Wheelchairs were examined for differences in fatigue life based on equivalent
      cycles. Unique survival curves were fit and compared for each wheelchair type.
      RESULTS: The UWs lasted the longest, with a mean of 309,362 equivalent cycles.
      The DWs faired the worst, with a mean of 117,210 equivalent cycles. The Kaplan
      Meier survival curves were significantly different (p < .001), with the UWs
      having the longest fatigue life. CONCLUSION: Fatigue life for UWs is
      significantly greater (p < .05) than LWs and DWs, indicating wheelchairs differ
      in durability.

PMID- 11588759
TI  - Understanding the special circumstances of our patients and their families.

PMID- 11588760
TI  - The relationship of resiliency to decision making and risk behaviors of cancer
      surviving adolescents.
AB  - Adolescents with a history of cancer frequently engage in risk behaviors. The
      purpose of this correlational study was to explore factors that affect decision
      making and risk behaviors (smoking, alcohol use, and illicit drug use) of cancer
      surviving adolescents. A sample of 52 teen survivors participated at two cancer
      centers. In addition to a medical record review and IQ testing, several
      psychosocial measures were administered in a semistructured interview with the
      teen survivor. Three antecedent factors (cognitive function, resiliency, and role
      modeling of risk behaviors by parents and peers) were examined in a hierarchical
      regression model to predict decision making. These same factors, with an
      additional mediating variable (decision making), were examined in a hierarchical
      logistic regression model to predict risk behaviors in teen survivors. In the
      decision-making model, adjusted for demographic covariates, resiliency was a
      marginally significant predictor of decision making. As non-resiliency increases,
      quality of decision making may decrease for teen survivors. In the model to
      predict risk behaviors, four factors (cognitive function, resiliency, role
      modeling, and decision making) were added to the basic model, controlling for the
      same covariates. Resiliency and decision making were highly significant
      predictors of one or more risk behaviors. Non-resilient teen survivors with poor
      quality decision making are more likely to engage in risk behaviors of substance
      use and need intervention that is aimed at improving decision-making skills to
      reduce these behaviors.

PMID- 11588761
TI  - Rural families' perspectives on having a child with cancer.
AB  - The goal of this study was to explore and describe the experience of being or
      having a child with cancer in a rural geographic area. An exploratory,
      descriptive study was conducted that used semistructured, in-depth, tape-recorded
      interviews as the primary data collection method. Ten rural families who each had
      a child with cancer formed the sample. Data were analyzed with qualitative
      analysis procedures. Families' descriptions revealed that their experiences were
      fraught with challenges that were due to living a great distance from the cancer
      treatment center. Descriptions of their experiences are presented in this report.
      Recommendations for health care professionals, particularly pediatric oncology
      nurses, to assist rural families in coping with their challenges are also
      offered.

PMID- 11588762
TI  - Using research to change practice: enteral feedings for pediatric oncology
      patients.
AB  - This report details a study whose purpose was to show the safety of and describe
      the clinical and financial outcomes of nasogastric (NG) and nasojejeunal (NJ)
      tube feedings for nutritional support during and after intensive treatment for
      cancer. During a 17-month period, NG or NJ tubes were inserted in 25 patients who
      experienced, or were anticipated to experience, suboptimal nutrition during or
      after their chemotherapy (n = 14), radiation therapy (n = 2), or chemotherapy
      plus radiation (n = 5), after bone marrow transplant (n = 2), and as a result of
      neurological impairment (n = 2). Patient ages ranged from 1 month to 14 years.
      NG/NJ tubes were used for a total of 1415 patient days (median 40 days). Of
      those, 756 days occurred in the hospital (median, 18 days) and 659 were
      outpatient days (median = 12 days). Total parenteral nutrition (TPN) was used
      during 104 patient days (range, 1 to 35 days), and combination NG/NJ feedings
      were given with TPN for a total of 101 days. A comparable number of days of TPN
      therapy for the NG-fed patients would have cost $177,390 (average $135/day),
      compared with $65,700 (average, $50/day) for enteral feedings, for a savings of
      $111,690. Ten patients experienced grade 2 to 3 diarrhea and/or vomiting during
      the study. No untoward outcomes were identified. Enteral feedings were found to
      be a safe and cost-effective method for providing nutrition to these children
      with cancer.

PMID- 11588763
TI  - Dapsone-induced methemoglobinemia in pediatric oncology patients: case examples.
AB  - Over the last 25 years, significant advances have been made in supportive care of
      the immunocompromised patient. One significant advance is the use of trimethoprim
      sulfamethoxazole (TMP-SMZ) in the prevention of Pneumocystic carinii pneumonia
      (PCP). Although TMP-SMZ remains the drug of choice for PCP prophylaxis, children
      who develop or have a history of adverse reactions must be prescribed an
      alternative treatment. In these instances, medications such as dapsone,
      aerosolized pentamidine, or atovaquone are prescribed. This report discusses four
      children with sulfa allergy who were prescribed dapsone and later developed
      methemoglobinemia. Although methemoglobinemia is associated with dapsone, there
      was no reference found regarding this link in the pediatric oncology literature.
      The purpose of these clinical examples is to alert the pediatric nurse and
      advanced practitioner to the association of dapsone and methemoglobinemia.

PMID- 11588764
TI  - A living legend in pediatric oncology nursing: Jean Fergusson. Interview by Kathy
      Ruccione.
AB  - Jean Fergusson is a true pioneer in pediatric oncology nursing. Her many
      professional accomplishments include working alongside Dr. Sidney Farber and
      others in the first pediatric Tumor Therapy Clinic in the United States,
      establishing a model pediatric nurse practitioner program that graduated an
      influential cadre of pediatric oncology nurse practitioners, publishing landmark
      papers about late sequelae of childhood cancer treatment, and serving as a role
      model and mentor to countless nurses over the past 50 years. Jean has brought all
      she is to her life as a nurse-she is gentle, funny, wise, easily moved, curious,
      generous, and, most of all, she truly loves children. An eyewitness to the
      dramatic changes in pediatric oncology over the decades, she herself is a
      survivor, having overcome dyslexia and other daunting life challenges. In this
      interview, Jean responds to questions about what shaped her interest in nursing
      and how she chose pediatric oncology, her impressions and recollections of the
      early days in pediatric oncology nursing, and her vision for the future of our
      specialty.

PMID- 11588765
TI  - Comforting and caring for a terminal patient.

PMID- 11588767
TI  - Laparoendoscopic approaches to occult gastrointestinal bleeding.
AB  - Identification of sites of small bowel hemorrhage remains a difficult problem.
      Endoscopy performed in association with surgery often proves successful when
      other attempts have failed. In attempts to minimize morbidity and even increase
      accuracy, surgeons have explored combining laparoscopic techniques with
      endoscopy. Although published experiences remain few, expectations remain high.

PMID- 11588768
TI  - Laparoscopic techniques in intestinal surgery.
AB  - Laparoscopic bowel surgery has developed slowly over the last decade, with
      virtually all procedures having been attempted with these laparoscopic
      techniques. The benefits of this approach to colorectal surgery have resulted in
      decreased lengths of stay, smaller incisions, and a potentially lower risk of
      small bowel obstruction. Resection of benign inflammatory disease presents
      particular challenges and may be expected to result in higher conversion rates.
      However, with increasing experience, even complicated diverticular disease and
      Crohn's disease can be managed laparoscopically. There is a growing body of data
      that suggests the early concerns regarding colon cancer resection, specifically
      port site recurrences, may have been exaggerated. Even more importantly, the
      early results of a number of prospective randomized trials are suggesting that
      survival and cure rates are not jeopardized by laparoscopic colectomy. The
      surgical techniques are demanding and require a level of standardization to
      achieve success. Laparoscopic colorectal surgery will have a definite role in the
      future.

PMID- 11588769
TI  - Laparoendoscopic treatment of gastric stromal tumors.
AB  - Gastric stromal tumors are the most common submucosal mass found in the stomach.
      These tumors are most often diagnosed at endoscopy and can be accurately
      characterized by endoscopic ultrasound. They typically require surgical
      resection, and an increasing number of patients undergo laparoscopic resection. A
      combined laparoscopic/endoscopic, intragastric enucleation technique is
      described, and results are reported in 10 patients. Eleven nonmalignant lesions
      were excised, with a mean size of 4.12 (2.0 to 7.0) cm. There were no
      complications, and the median length of stay was 3.5 days. This surgical approach
      appears appropriate for predominantly intraluminal, benign-appearing lesions of
      the proximal stomach.

PMID- 11588770
TI  - Laparoendoscopic approaches to enteral access.
AB  - Access to the stomach for long-term enteral feeding or decompression can be
      achieved with numerous methods. The methods include laparotomy, gastroscopy,
      laparoscopy, and fluoroscopy. All methods have been shown to be safe and
      effective. Percutaneous endoscopic gastrostomy (PEG) was introduced by Ponsky in
      1990, and laparoscopic gastrostomy was introduced 10 years later. PEG rapidly
      replaced open gastrostomy as the method of choice for enteral nutrition. The
      laparoscopic alternative was ideal for patients who were not candidates for PEG
      placement. The laparoscopic or laparoendoscopic placement of enteral tubes allows
      visualization of the intestinal tract to ensure proper tube positioning. Many
      patients are not candidates for a PEG because of head and neck cancer, esophageal
      obstruction from stricture or carcinoma, large hiatal hernia, gastric volvulus,
      overlying intestine or liver, facial trauma with wired mandible, or severe
      stomatitis secondary to radiation therapy. Lastly, laparoscopy lessens the chance
      of injury to the surrounding structures, adhesions can be safely lysed, and
      metastatic or concomitant disease may be identified. This report will review the
      numerous methods available to the laparoscopic surgeon for gaining access to the
      stomach or intestine.

PMID- 11588771
TI  - Laparoendoscopic approaches to common bile duct stones.
AB  - Since the advent of laparoscopic cholecystectomy, there has been a debate
      regarding the most effective approach to intraoperative management of
      choledocholithiasis. Although transcystic duct extraction has been effective, the
      integration of flexible endoscopic methodology into the laparoscopic procedure
      has facilitated management of difficult cases. Variations of endoscopic
      retrograde cholangiopancreatography may be used during laparoscopic
      cholecystectomy or facilitated after the surgery by maneuvers at the time of
      operation. These techniques have been extremely effective in facilitating the
      laparoscopic treatment of common bile duct stones.

PMID- 11588772
TI  - Endoscopic therapy for gastroesophageal reflux disease.
AB  - There are many options regarding the treatment of gastroesophageal reflux disease
      (GERD). This report reviews the safety, efficacy, and early results of the
      various treatment options, with a focus on endoscopic therapy for GERD. This
      approach, which is still in its infancy, is viewed as cost-effective without the
      associated morbidity of surgery and the necessity of long-term compliance with
      medical therapy.

PMID- 11588773
TI  - Laparoendoscopic approach to pancreatic pseudocysts.
AB  - The indications and timing for pseudocysts drainage have evolved, as well as the
      role for percutaneous, endoscopic, or surgical drainage. Of the many treatment
      options available to patients with pancreatic pseudocysts, laparoscopic drainage
      is becoming more widespread because it allows for definitive drainage with faster
      patient recovery.

PMID- 11588774
TI  - Overview of infection control problems: principles in gastrointestinal endoscopy.

PMID- 11588775
TI  - [NEURON simulation of nerve functions].

PMID- 11588776
TI  - [Feasibilities of MRI imaging in diagnosis of joint diseases].

PMID- 11588777
TI  - [Pathogenesis of arterial hypertension in the Itsenko-Cushing syndrome].
AB  - The search and measurements of the activity of angiotensin-converting enzyme
      (ACE) and glucocorticoid receptors of type II (GR II) were made in the adrenals
      of 19 patients with Icenko-Cushing syndrome (ICS). ACE and GR II were detected in
      the tissues of the adrenal cortex and cortisol-producing tumors. It is suggested
      that glucocorticoids may induce ACE activity and in this way potentiate synthesis
      of angiotensin II. The effect is mediated by GR II. Activation of such tissue
      components of the renin-angiotensin system contributes much to the mechanism
      underlying arterial hypertension.

PMID- 11588778
TI  - [Effects of perstarium on the systolic and diastolic functions of the myocardium
      in patients with chronic cardiac failure].
AB  - The aim of the study was to assess prestarium effects on systolic and diastolic
      cardiac functions in 38 patients with ischemic heart disease and chronic cardiac
      failure (NYHA functional class II-IV) by biventricular balanced
      radioventriculography. Both left and right ventricular diastolic dysfunction was
      found. A course of prestarium treatment caused different alterations in
      ventricular contractility. 64.2% patients of those who had right ventricular
      ejection fraction < 40% achieved an increase in right and left ventricular
      ejection fraction. Improved diastolic function of the myocardium was registered
      in 71% patients.

PMID- 11588779
TI  - [The course of infectious endocarditis in IV drug abusers and in subjects
      predisposed to heart diseases].
AB  - 40 patients with infective endocarditis (IE) abusing intravenous drugs (heroin,
      opium surrogates) and 9 IE patients predisposed to heart diseases were examined
      by Duke diagnostic criteria. IE in drug abusers is characterized by acute course
      of the disease with affection of the intact valves of the right heart (97.5%) and
      septicemia provoked by high-virulent microflora (Staph. aureus in 65%). Drug
      abusers showed the following principal clinical syndromes of IE: thromboembolic
      (65%); septic with formation of acute DIC syndrome (75%), development of
      pyodestructive foci in the organs and polyorganic insufficiency (23.3%); acute
      circulatory insufficiency (37.5%); secondary nephropathy (100%). In IE abusers
      with predisposition to heart diseases IE ran subacutely in the presence of
      bacteriemia caused by low-virulent microflora (Strept. viridans in 11%) or in the
      absence of microbial growth in blood seeding (78%). High IE lethality in drug
      abusers (40%) is explained both by severe complications and concomitant diseases
      (viral hepatitis B and C, HIV infection, etc.).

PMID- 11588780
TI  - [Symptoms of a prodromal period in unstable angina pectoris].
AB  - Long-term investigation of 67 patients with unstable angina pectoris (UAP)
      focused on frequency of non-specific symptoms occurring within 3 days before a
      significant rise in the frequency of anginal attacks. Nonspecific clinical
      symptoms seem either to appear or enhance prior to emergence of UAP. Moreover,
      these symptoms in many patients repeat before each episode of UAP.

PMID- 11588781
TI  - [Central hemodynamics and microcirculation in hypertensive patients with
      influenza or other acute respiratory viral infections].
AB  - Integral rheography and conjunctival biomicroscopy studied central hemodynamics
      (CH) and microcirculation (MC), respectively, in 37 hypertensive patients with
      influenza and acute respiratory viral infection (ARVI) and 38 normotensive
      patients with influenza and ARVI aged 41 to 94 years (group 1 and 2,
      respectively). In group 1 vs group 2 specific peripheral resistance was
      significantly higher, intravascular changes were more manifest (disseminated
      aggregation of red cells, slow blood flow with its incomplete block. It is shown
      that patients with influenza and ARVI had main functional circulatory disorders
      in microcirculation zone. The study of microcirculation by conjunctival
      biomicroscopy is important for these patients for assignment of pathogenetically
      sound vascular therapy, first of all disaggregants.

PMID- 11588782
TI  - [Soluble receptors of TNF-alpha in rheumatoid arthritis].
AB  - The serum level of soluble TNF-alpha receptors with molecular mass 55 kDa (sTNF
      a55R) was measured by enzyme immunoassay with commercial kits in 30 patients with
      rheumatoid arthritis (RA) and 38 healthy donors. High sTNF-a55R serum levels were
      registered in 90% of RA patients. These levels correlated with RA activity by
      DAS. Thus, assay for sTNF-a55R can be used for assessing RA activity.

PMID- 11588783
TI  - [Effects of glucose inhalations on bronchial reactivity in bronchial asthma].
AB  - Twenty-one patients with asthma were examined in order to evaluate the effect of
      glucose inhalations on bronchial hyperreactivity. Plasma glucose, erythrocyte
      glycosylated hemoglobin, and glucose membrane transport in erythrocytes were
      evaluated. Acetylcholine test was carried out after inhalation of 5% isoosmolar
      glucose solution with evaluation of bronchial sensitivity and reactivity.
      Inhalations of glucose solution in atopic asthma can affect the bronchi by
      changing their hyperreactivity. This effect will be used for developing a new
      therapeutic approach to treatment of asthma.

PMID- 11588784
TI  - [The role of hemodynamic crisis in the etiology and pathogenesis of stroke:
      current views].

PMID- 11588785
TI  - [Efficiency of laser therapy in patients with nonspecific pulmonary diseases].
AB  - Generation of active oxygen forms (AOF) in whole blood was studied in 63 patients
      with acute pneumonia and 72 asthmatics by chemiluminescence (CL) registration. CL
      intensity depended on the intensity of inflammatory process. Groups of patients
      with high and low blood CL were distinguished. In 35 patients intravascular laser
      exposure of the blood (ILEB) was added to therapeutic complexes. Disorders of
      free radical oxidation persisted for a long time in the majority of patients with
      high CL of the blood, treated by ILEB; in many cases the inflammatory process
      acquired a protracted pattern. By contrast, in patients with low intensity of
      blood CL, ILEB stimulated the generation of AOF and increased the treatment
      efficiency. Hence, whole blood CL can serve as a criterion of ILEB prescription
      and can be used for monitoring the patient's status during laser therapy.

PMID- 11588786
TI  - [Acid producing function of the stomach in patients with duodenal ulcer and
      diabetes mellitus].
AB  - We studied gastric secretion in submaximal and maximal histamine and pentagastrin
      tests, computer-assisted pH-metry, chromogastroscopy and chromoduodenoscopy in
      205 patients with duodenal ulcer (DU) and diabetes mellitus (DM). DU patients
      with DM type I had low acid gastric secretion in the stimulated phase, an
      excitable type of gastric secretion, continuous acid-formation of low intensity,
      subcompensated acid-neutralizing function of the antral portion of the stomach,
      normoacidic state. DU patients with DM type II had low fasting acid gastric
      secretion, an inhibitory type of gastric secretion, normal acid-formation,
      compensated acid-neutralizing function of the antral portion of the stomach,
      hypoacidic state.

PMID- 11588787
TI  - [Evolutionary trends in symptoms of acute glomerulonephritis in adult population
      of the Novosibirsk region].
AB  - Acute glomerulonephritis (AGN) trends in the last 3 decades in the Novosibirsk
      Region have been analysed basing on the data from 308 AGN case histories. The
      results of the analysis demonstrate that AGN occurs not often but with stable
      rate. It is encountered more frequently in young men. The last decade is
      characterized by higher morbidity after streptococcal infection, high percentage
      of women at reproductive age, aggravation of the clinical course with marked
      edemas, severe arterial hypertension, renal dysfunction (acute renal failure in
      10.4%), cases of left ventricular failure (5.2%) and eclampsia (1.7%) not
      registered earlier.

PMID- 11588788
TI  - [Efficiency of quamatel in combination with device sound stimulation of the
      gastroduodenal zone in ulcer patients].
AB  - 24-hour monitoring of gastric juice pH and esophagogastroduodenoscopy with biopsy
      and test for H. pylori (HP) were conducted in 117 patients with ulcer before and
      after treatment with famotidine (quamatel, Hungary) and device sound stimulation
      (DSS). Combined eradication therapy (quamatel 40 mg/day, metronidazole 500 mg 4
      times a day, amoxicilline 750 mg 3 times a day, DSS) eradicated HP in 100% of
      patients with gastric ulcer and 91.7% of patients with duodenal ulcer. Scarring
      of the ulcer defect occurred for 11.8 +/- 1.1 and 15.3 +/- 1.4 days,
      respectively. These results are better than those of monotherapy with quamatel or
      DSS.

PMID- 11588789
TI  - [Effectiveness of fenspiride in patients with chronic obstructive bronchitis].
AB  - Patients with chronic obstructive pulmonary disease of moderate severity were
      investigated for two months for assessment of fenspiride activity. Examination of
      the patients (age 42.6 +/- 5.3) took place before and after fenspiride therapy.
      In comparison to the control group, fenspiride patients showed improvement of
      external respiration function: FEV 1, FVC, FEF 50-75, PEF increased. Dienic
      conjugates, malonic dialdehyde levels decreased, alpha-tocopherol in platelet
      membranes rose, functional activity of platelets fell. Side effects were rare and
      not serious. It is concluded that fenspiride has an antiinflammatory effect,
      reduces bronchoconstriction and depresses platelet aggregation, is well
      tolerated. Fenspiride is an effective drug for the treatment of moderate chronic
      obstructive bronchitis.

PMID- 11588790
TI  - [Family resistance of receptors to glucocorticoids].

PMID- 11588791
TI  - [Psychosomatic trends in general medical practice].

PMID- 11588792
TI  - [Why do Prinzmetal's angina attacks occur in sleep?].

PMID- 11588793
TI  - [National conference "Free radicals and human diseases"].

PMID- 11588794
TI  - [Famous scientists and scientific schools of the Graduate school of the Russian
      Medical Academy].

PMID- 11588795
TI  - [The effects of antihypertensive drugs on lipid metabolism. Part I. Diuretics,
      beta-blockers, calcium antagonists].

PMID- 11588796
TI  - A developmental and psychobiologic framework for understanding the role of
      culture in child and adolescent psychiatry.
AB  - In summary, despite these widely accepted interdisciplinary perspectives on the
      role of culture, the DSM framework lacks a culturally meaningful usage. For
      Kleinman, the changes on culture in the DSM-IV were "too little, too late." The
      cultural formulation and a glossary of culture-bound syndromes were included in
      its appendix. The acceptance by the DSM-IV task force of the notion of cultural
      variations in clinical presentation of disorders may be reflective of changes to
      come in the future. The current DSM-IV has more of a descriptive psycho
      pathologic approach rather than an integrated cross-cultural, psychobiologic,
      developmental approach, however. The developmental perspective in psychiatry is
      emerging as a "bridge" for consilience through evidence-based scientific
      understanding and conciliation through clinical practice. This perspective is
      unique because it is intrinsic to different aspects of psychiatry. It readily
      accommodates the descriptive-empirical model by means of concepts borrowed from
      developmental psychopathology and psychobiology. These concepts include normalcy,
      life cycle, risk and resilience, and protective mechanisms within a dynamic
      construction of development that involves an interchange among biology-person
      society-culture. The developmental perspective also can make important
      contributions to a process-oriented approach to measurement beyond a textually
      defined DSM structure. The developmentally operationalized dimensional constructs
      offer to expand psychiatry's domains beyond diagnosable conditions and illness
      boundaries. The developmental perspective argues for early preventive and
      therapeutic interventions for a broad array of applications based on demonstrated
      evidence of efficacy. Finally, the developmental perspective with its social and
      cultural contexts is an intrinsic complement to Kandel's framework for an
      expanded training of psychiatrists in the neurosciences and the associated
      innovative technologies for understanding the mechanism of structural and
      functional changes in the brain in various contexts and categories.

PMID- 11588797
TI  - Cultural competence and sensitivity. Getting it right.
AB  - In our search for equality in a heterogeneous society, we must remember that
      equality does not mean the same, it means balance. We must respect the need for
      others, particularly persons who hold membership in oppressed groups, to
      reconstruct and reconnect with their own worldviews. When we do this we help
      create opportunities for individuals and groups to discover their unique
      qualities rooted in a shared world view. Ultimately, this practice will lead to a
      healthier and more holistic heterogeneous cultural experience. The goal is not to
      adopt the worldview of others but to learn about the view of others, respect
      those views, and use that knowledge as a foundation for creating culturally
      competent advocacy and practice methods.

PMID- 11588798
TI  - Community factors supporting child mental Health.
AB  - A principal purpose of this article has been to examine the gap between research
      and practice in relation to community factors in child mental health. Two caveats
      were introduced in preparation for this assessment. First, it was pointed out
      that the definition of communities has been expanded by considering the
      organizing properties of social aggregates that are not simply a function of the
      race, ethnicity, or social class of individuals who compose them. Having these
      definitions grounded in theory substantially advances the needs of research and
      the design and goals of community-level interventions. The second caveat relates
      to the boundaries of the disciplines that cater to the needs of children. During
      the same era when child psychiatry is largely occupied with placing psychotropic
      medications at the center of clinical approaches, there is an important effort in
      child psychology and sociology to cut across their disciplinary confines to form
      more comprehensive designs that are sensitive to experiences and circumstances
      that emerge from specific aspects of community context. Research from the PHDCN
      was used as an example of this new interdisciplinary approach. Several community
      based research projects were selected for review based on their clear
      implications to improve context-sensitive assessment of child mental health and
      design effective community-based interventions to improve child mental health.
      The Healthy Start and CATCH programs indicate that involving child professionals
      at the grassroots of community life requires skill and patience but that the
      effort is satisfying and potentially effective. Other examples, exemplified by
      North Carolina's Smart Start initiative and the program of developmental assets
      from the Search Institute, demonstrate coherent approaches that provide a
      foundation for long-term capacity building in assessment, local decision making,
      and the design and evaluation of interventions. Three conclusions are warranted
      from this discussion. The first conclusion suggests that research in child
      development generally, and child mental health specifically, does not incorporate
      the social ecology of the child is seriously flawed. There is a broad recognition
      within most sectors of society that the quality of civic engagement is of
      critical importance to community efforts to improve the health and well-being of
      children. This is true for all communities and families, regardless of their
      levels of material wealth and educational achievement. It is also well understood
      that poverty undermines the well-being and life chances of children. For this
      reason, the third conclusion requires that intensive, sustained efforts be made
      to eradicate poverty and reverse the current economic trend toward growing
      economic disparity. The implications of this knowledge for the practice of child
      psychiatry are not new ones. In many ways, they advocate for a re-examination of
      the historical roots of the field as it defined approaches to juvenile justice,
      school counseling, and early intellectual enrichment for economically
      disadvantaged preschool children. All these efforts were sensitive to children's
      social environment, and child psychiatrists viewed their success in taking on the
      challenges of changing schools, courts, and community and family environments.
      These challenges hardly have been overcome. The requirements of understanding and
      evaluating community supports for children are a fundamental component in the
      training and practice of child psychiatry. To quote the U.S. Surgeon General in a
      preamble to the recent Report on Child Mental Health: One way to ensure that our
      health system meets children's mental health needs is to move toward a community
      based health system that balances health promotion, disease prevention, early
      detection and universal access.

PMID- 11588799
TI  - Cultural influences on diagnosis.
AB  - Contemporary child psychiatry has both embraced the relevance of culture to
      diagnosis (in endorsing cultural competence) and taken a largely culture-blind
      approach to classification (in adopting the Diagnostic and Statistical Manual of
      Mental Disorders-IV). Different kinds of diagnoses serve different purposes in
      child psychiatry: classification, understanding the child, and guiding
      intervention. All discourse about diagnosis is shaped by culture, especially
      aspects of culture that may be difficult to acknowledge. Integration of the role
      of culture into clinical practice is facilitated by balancing the use of
      categorical diagnoses with consensus-based assessment, including acknowledgment
      of the relative positions of clinician and child.

PMID- 11588800
TI  - Cultural considerations in the treatment of children and adolescents.
      Operationalizing the importance of culture in treatment.
AB  - Culture is complex and fluid, constantly changing with the tides of internal and
      external influence. It is vital for the transcultural therapist to understand the
      roles, context, and therapeutic consequences that follow from culture. The
      constructs mentioned previously are interdependent and often inseparable from one
      another. The interwoven web of political, social, and cultural constructs must be
      considered to understand the context of mental illness. This being said,
      therapists should not be content with the broad brush of cultural definition.
      Subcultural and intracultural dynamics also may play a role in a patient's world
      view, and the therapist must remain open to these variations. Likewise, one
      should be careful of stereotype. Culture plays a vital role in shaping physical
      and psychological conceptions but in and of itself cannot define an individual.

PMID- 11588801
TI  - Systems development of child mental health services in developing countries.
AB  - This article reviews recent findings in the epidemiology of childhood psychiatric
      disorders in the developing world and the relationship of epidemiology to system
      development. Examples of systems developed in the Third World are discussed. The
      experience with attention-deficit/hyperactivity disorder and the development of a
      comprehensive system of care around it in Lebanon are described. Cultural factors
      that affect special populations in childhood mental health are examined. The
      article concludes with recommendations for systems development in Third World
      countries.

PMID- 11588802
TI  - Cross-cultural issues in research on child mental health.
AB  - This article describes and discusses the major challenges in cross-cultural
      research on child mental health. Based on a literature review, the article
      summarizes limitations of past research in this area. Possible conceptualization
      and operationalization of culture and approaches to derive cross-culturally
      equivalent methods are discussed.

PMID- 11588803
TI  - Suicide in response to changing societies.
AB  - The "medical model" is an insufficient explanation for the high suicide rates,
      but it does not mean that suicide is a different phenomenon in China. A
      multidimensional model (Fig. 6) is proposed to appreciate better the complexity
      of the problem, which can be applied to other countries. As in Figure 6, suicide
      and suicide attempts are conceptualized as a continuum of behaviors. The suicide
      method may modify the boundaries (i.e., the availability and choice of a lethal
      method may expand the size of completed suicides and vice versa). The spectrum of
      behaviors is also under the influence of individual factors, such as psychiatric
      disorders and personality, and local factors, such as local cultural norms,
      resources, and familial problems. All of these factors are subject to the
      influence of greater social forces. For example, psychiatric disorder increases
      the risk of suicide but is shaped by global forces. In the case of China, the
      importing of Western values influences the way Chinese people present their
      idioms of distress. Chinese people who tend to somatize start to psychologize
      more, [figure: see text] which in turn affects the rates of depression and
      subsequently the risk of suicide. The various factors also interact with one
      another. The diagnosis of disruptive and antisocial disorder illustrates how
      local factors modulate that of the individual. In Diagnostic and Statistical
      Manual of Mental Disorders, conduct disorder is defined by a series of "socially
      unacceptable behaviors," including aggression, destruction of property, theft,
      and violation of rules. Because biologic validity is lacking, the diagnosis (an
      individual factor) may vary widely in different cultural settings (a local
      factor). In China, conformity, self-control, and discipline are emphasized;
      subthreshold cases in the West already may be unacceptable in the Chinese setting
      and be labeled "disruptive." On the other hand, the cultural emphasis on
      conformity in the upbringing may reduce the display of such behaviors and lead to
      a lower prevalence of disruptive and antisocial disorders in China. With
      globalization, however, the "Chinese" values are more closely identified with the
      global culture, and a rising trend of personality disorders has been witnessed.
      The media are some of the powerful agents in transmitting these forces. The
      medical model of explaining the phenomenon of suicide with psychiatric disorders
      is not entirely satisfactory. The association of a high suicide rate with a low
      prevalence of psychiatric disorders in China challenges this conventional view.
      Rather than refuting this conventional model, the dynamic interaction with local
      sociocultural factors and global forces is emphasized. Empirical evidence is
      lacking, however, and should be the focus for future suicide research.

PMID- 11588804
TI  - The psychosocial impact of armed conflict on children. Rethinking traditional
      paradigms in research and intervention.
AB  - It is undeniable that the impact of war on children is a significant issue that
      merits continued efforts in research and intervention. It is time for a shift in
      paradigms; instead of focusing solely on exposure to traumatic events and
      defining pathology per dominant diagnostic criteria, it is essential that
      research turn to examining the effect of chronic stressors and exploring how
      certain mechanisms may be protective or act to moderate the psychosocial impact
      of war on children. The role of such protective mechanisms must be examined for
      differences by development and gender and by cultural context and the nature of
      the conflict situation itself. Investigations of the health and psychosocial well
      being of war-affected children and the programs that serve them must attend to
      the restoration of basic physiologic needs, safety, structure, familial ties, and
      other sources of support and integration of cultural practices of healing. The
      coping efforts of young people and their families and the creation of more
      positive roles for youth also must be explored. Addressing these fundamental
      issues in research and programming will go a long way in fostering new
      opportunities for peace, healing, and the promotion of mental health and well
      being for war-affected children in modern times.

PMID- 11588805
TI  - The impact of social change on child mental health in Eastern Europe.
AB  - The transition of the Eastern European countries in the past 12 years from
      totalitarian, communist societies to democratic societies has had a broad impact
      on children's mental health, both positively and negatively. This transition has
      not been without economic difficulties. All countries in the region experienced a
      significant deterioration of output that has affected the availability of
      commodities and services. Although recovery has been achieved in some Eastern
      European countries and is in progress in other countries, reversal of the
      cutbacks in allocations to necessary services that protect children and families
      may take longer to achieve. Movement toward a free market economy and greater
      individualism also has focused attention away from the role of society to protect
      and provide care for its citizens, especially the most vulnerable. On the
      positive side, mental health, as a concept for children and adults, comes to be
      appreciated only in a society that values and safeguards individual rights.
      Democratic process within the family, the depoliticization of mental illness, the
      passage of laws assuring basic children's rights, services for and public
      awareness about children abuse, reforms in education, the proliferation of mental
      health clinics and support centers, and the resumption of training of mental
      health professionals all set a tone to first consider, then assure, the positive
      development of children's mental health.

PMID- 11588806
TI  - Child rights and mental health.
AB  - This article introduces the principles and articles of the United Nations
      Convention on the Rights of the Child (CRC) and discusses the implications of
      this new conceptualization of childhood for child mental health. Consistent with
      the articles of the CRC, Canadian and US health administrations call for
      including the perspectives and participation of children in promotion of their
      own mental health and in the planning of mental health services. Examples of the
      incorporation of the CRC into programs and services for children and youth are
      described.

PMID- 11588808
TI  - [Effect of Palomo procedure on the quality of the semen in infertile patients
      with varicocele and oligoastenospermia].
AB  - OBJECTIVE: To evaluate the effect of Palomo's surgery on the semen quality from
      oligospermic infertile men with varicocele. STUDY DESIGN: Retrolective cohort.
      SETTING: Hospital General Regional No. 1, IMSS, Culiacan, Sinaloa. PATIENTS: 39
      oligospermic infertile men with varicocele. INTERVENTIONS: Palomo's surgery.
      MEASUREMENTS: A spermatobioscopy before the Palomo's surgery was performed, and
      after the surgery two spermatobioscopies in different times of six months.
      RESULTS: Spermatobioscopy before the surgery: Concentration/mL = 8.8 +/- 4.1
      millions, Motility = 19.5 +/- 10.0%, Vitality = 66.2 +/- 14.4%. First
      spermatobioscopy after surgery: Concentration/mL = 29 3 +/- 18 3 Motility = 41 5
      +/- 19 1, Vitality = 74.7 +/- 14.5. Second spermatobioscopy after surgery:
      Concentration/mL = 14.6 +/- 10.3, Motility = 28.0 +/- 14.8, Vitality = 78.7 +/-
      16.8. All differences from the spermatobioscopy before the surgery were
      significant. CONCLUSION: Palomo's surgery has a favorable effect on the quality
      of the semen, with a diminishing trend in concentration and motility in the
      second semester after the surgery. The pregnancy rate was 15%.

PMID- 11588807
TI  - [Giant cyst of the ovary. Report of a case].
AB  - A 38 year old woman nulligravida was admitted with increased abdominal girth for
      two years, an ultrasound revealed diagnosis of an ovarian cyst, at laparotomy we
      found a left giant ovarian cyst; hysterectomy was performed, there were no
      complications. Pathology reports an ovarian serous cystadenoma weighting 30 kg
      and uterine fibroids, Postoperative course was uneventful. In spite of accessible
      diagnostic imaging as ultrasound, we still find cases as the one we had
      described. There has not been reported a mass of this weight in our Institution
      before.

PMID- 11588809
TI  - [Insulin resistance index: measurement and potential in human reproduction].
AB  - Insulin resistance (IRI) applies to abnormalities of insulin-stimulated glucose
      metabolism. Biochemical events related to this phenomenon are difficult to search
      in the absence of overt diabetes mellitus. A simple method to quantify insulin
      resistance was assessed through the measurement of glucose and insulin (fasting
      glucose [mmol/L] x fasting insulin [mU/L]/22.5) in patients (n = 50) attending
      our clinic of human reproduction, including controls (n = 10) and diabetics
      either unstable or under control (n = 5). Cases with obesity, polycystic ovarian
      disease, diabetes mellitus, infertility and hypoglycemia showed higher (p = 0.01
      0.05) IRI changes, inversely correlated with a decreasing fasting glucose
      observed in diabetics under treatment with various degrees of control. We
      conclude that the IRI method used in this work is a reliable estimate of insulin
      resistance with potential applications for the study of reproductive biology.

PMID- 11588810
TI  - [Frequency of Gardnerella vaginalis vaginosis and its association with other
      pathogens causing genital infections in the female].
AB  - In order to determine the presence of unspecific vaginosis and their causes, 700
      vaginal smears were obtained from patients assisting to the Clinical Laboratory
      of the Familiar Medicine Unit No. 28 "Gabriel Mancera" of the Instituto Mexicano
      del Seguro Social, during 6 months. The patients age was from 18 to 55 years old.
      To establish the infectious etiology of these pathologies the vaginal smears were
      observed freshly and stained by Gram's method. Specific test for differentiate
      Gardnerella vaginalis and Candida albicans were also performed. From 700 vaginal
      smears, 160 were positive to Candida albicans (22.86%); 150 to Gardnerella
      vaginalis (21.43%); and 14 to Trichomonas vaginalis (2%). The most frequent
      association were Candida albicans with Gardnerella vaginalis in 14 women, who 12
      had a reduced number of pregnancy, and 7 had only one pregnancy (58.3%). The age
      groups most affected were between 18 and 35 years old, corresponding to the
      reproductive stage of the woman. Gardnerella vaginalis predominated in the 30-35
      years old group.

PMID- 11588811
TI  - [Blood concentrations of calcium and magnesium in women with severe pre
      eclampsia].
AB  - Abnormalities in the calcium and magnesium metabolism may participate in the
      pathogenesis of preeclampsia. Serum levels of magnesium, calcium, sodium,
      potassium and chlorine were measured in 15 pregnant women with severe
      preeclampsia and 20 uncomplicated pregnant women. Serum sodium, potassium and
      chlorine concentrations were similar in both groups. Nevertheless, serum
      magnesium levels were significantly elevated in severe preeclamptic women
      relative to women with uncomplicated pregnancy. The serum calcium concentration
      and calcium/magnesium ratio were not differences in the preeclamptic and the
      healthy pregnant woman.

PMID- 11588812
TI  - [Germinal cancer of the ovary and pregnancy].
AB  - The association of ovarian cancer with pregnancy, in a young patient with acute
      abdominal syndrome was reviewed. The prognosis is related to early diagnosis and
      the stage, therefore ultrasonography is the corner stone to detect these tumors
      allowing a conservative management, mainly when the fertility must be maintained
      in younger patients. Chemotherapy is an excellent adjuvant in the midtrimester
      and can be administered without an important deleterious effect on the fetus.

PMID- 11588813
TI  - Acupuncture in dentistry.

PMID- 11588814
TI  - Treatment under i.v. sedation.

PMID- 11588815
TI  - House of Lords debate. Dental sedation.

PMID- 11588816
TI  - Cloning and characterization of a gene encoding an immunosuppressive factor from
      Actinobacillus actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans is a pathogen of localized juvenile
      periodontitis and adult periodontitis. Immunomodulating activity is generally
      thought to be important in colonization by such pathogenic bacteria. Among the
      proteins possessing these activities, a 14 kDa immunosuppressive factor of A.
      actinomycetemcomitans has been reported by Kurita-Ochiai and Ochiai (Infect Immun
      64: 50-54, 1996). To evaluate this factor, we cloned and characterized the gene
      encoding it. The immunosuppressive factor was screened from a genomic library of
      A. actinomycetemcomitans using an oligonucleotide probe based on the amino acid
      sequence of the factor. The clone obtained, pHI13, contained a 1.5 kbp fragment.
      The immunosuppressive factor located in its center. Southern blot analysis showed
      that this factor is common among A. actinomycetemcomitans strains. The open
      reading frame consisted of 324 bp coding for 107 amino acid residues. The
      relative molecular mass of the deduced amino acid sequence was calculated to be
      11,595. BLAST analysis indicated that the amino acid sequence is highly
      homologous with those of thioredoxins from Haemophilus influenzae (76.6%),
      Neisseria meningitidis (67.3%), and Pseudomonas aeruginosa (59.3%). These results
      suggest that the 14 kDa immunosuppressive factor characterized in this study is a
      thioredoxin.

PMID- 11588817
TI  - A lip seal study of Japanese children with malocclusion.
AB  - The purpose of this study was to clarify the relationship between lip seal and
      malocclusion in Japanese children. Fifty-three patients aged 7 to 14 years (mean
      10.24 +/- 1.93) were selected randomly, and compared with 20 subjects with normal
      occlusion aged 7 to 14 years (mean 10.50 +/- 2.56). The subjects were divided
      into a good lip seal group and poor lip seal group by observing the distance
      between the upper and lower lip at rest. The variables that were analyzed for
      morphological evaluation included model analysis and cephalometric analysis.
      Noted for functional evaluation were tongue position, the size of the tonsils and
      adenoids and the oral muscle force measured by button pulling. In the evaluation
      of the degree of lip seal, there was no statistical difference between subjects
      with malocclusion and those with normal occlusion. Within the group with
      malocclusions, however, there were significant differences in overbite (p <
      0.01), overjet (p < 0.01), and oral muscle force by button pulling (p < 0.05)
      between the good lip seal and poor lip seal groups. These results suggest that
      there is a need not only to correct malocclusion but also to be aware of lip
      sealing so that it may be improved in Japanese children.

PMID- 11588818
TI  - The Nd-YAG laser is useful in prevention of dental caries during orthodontic
      treatment.
AB  - Plaque control during the course of orthodontic treatment is not an easy task,
      and dental caries are not an unlikely complication. We examined the possibility
      of controlling dental caries with Nd-YAG laser irradiation in orthodontic
      patients. As a preliminary experiment, we used the Nd-YAG laser to irradiate an
      extracted tooth and then left it to soak in lactic acid. The decay of the tooth
      was evaluated with a scanning electron microscope (SEM); tooth decay was
      inhibited by the action of the laser. Twenty patients undergoing orthodontic
      treatment for early decalcification of the teeth (white spot lesions) were
      selected, and photographs were taken of their oral cavities. White spot lesions
      on the four incisors and two canines of the maxilla were traced on tracing paper,
      and their areas were calculated by computer. Ten of the patients received laser
      treatment and acidulated phosphate fluoride solution (APF); the other ten acted
      as the control group. Between 11 and 12 months later, we photographed the oral
      cavity as we had previously; the white spot lesions were again traced and their
      areas calculated. The changes in the areas of the white spots of the laser
      irradiated and control groups showed the following increases: laser-irradiated
      group, 1.41 times; controls, 2.87 times. The difference was statistically
      significant. These results demonstrate that Nd-YAG laser irradiation with
      application of APF acts as an effective method of caries control during
      orthodontic treatment.

PMID- 11588819
TI  - Clinicostatistical study of ameloblastoma treatment.
AB  - The purpose of this study was to investigate the treatment of 190 cases of
      ameloblastoma in our department from 1966 to 1994. The statistical results with
      regard to age, sex and region agreed with those of other investigators. Thirty
      five of 43 (81.4%) cases underwent enucleation in 1960s, but the sixteen of 27
      (59.3%) cases underwent partial resection of mandible in 1990s. The defect of
      mandible was reconstructed with iliac bone grafting since 1968, grafts with a
      mixture of iliac blocked bone and PCBM (particulate cancellous bone and marrow)
      have been used since 1975. Grafting of the inferior alveolar nerve with the great
      auricular nerve to the defect has been performed in our department since 1977.
      Recently, technique involving pull-through of the inferior alveolar nerve bundle
      has been used in our department. When the reconstruction method for the mandible
      and nerve has been established, it becomes possible to operate radically and
      positively. Recurrence occurred in 17 cases after the primary enucleation. It is
      thought that the primary treatment of ameloblastoma must be as radical as
      possible. It appears to be necessary to observe progress and perform follow-up in
      cases of ameloblastoma for more than ten years, because there was one recurrence
      at 9 years and 4 months after the first operation. In fact, three quarters of our
      cases were lost to follow-up. Such losses can problems in confirming recurrence
      and responding rapidly.

PMID- 11588821
TI  - The acellular dermal matrix: soft-tissue development for dental implants.

PMID- 11588820
TI  - Effect of weak electric current on reducing oral bacteria in vitro.
AB  - The ions generated by weak electric current may be used for removal of dental
      plaque. Also, it has been judged from changes in the viable bacterial cell count
      and the amount of adenosine triphosphate (ATP) in the saliva that the passage of
      such a current also has a bactericidal effect on the oral microflora. We
      confirmed in vitro that 0.5 and 1.0 mA currents that passed for 10 min through
      phosphate buffered saline containing salivary bacteria were effective in killing
      the bacteria.

PMID- 11588822
TI  - Characterization of preferential flow in undisturbed, structured soil columns
      using a vertical TDR probe.
AB  - Rapid movement of agricultural chemicals through soil to groundwater via
      preferential flow pathways is one cause of water contamination. Previous studies
      have shown that time domain reflectometry (TDR) could be used to characterize
      solute transport in soil. However, previous studies have only scarcely addressed
      preferential flow. This study presents an extended application of TDR for
      determining preferential flow properties. A TDR method was tested in carefully
      controlled laboratory experiments using 20-cm long and 12-cm diameter
      undisturbed, structured soil columns. The method used a vertically installed TDR
      probe and a short pulse of tracer application to obtain residual mass (RM)
      breakthrough curves (BTC). The RM BTC obtained from TDR were used to estimate
      mobile/immobile model (MIM) parameters that were compared to the parameter
      estimates from effluent data. A conventional inverse curve fitting method
      (CXTFIT) was used to estimate parameters. The TDR-determined parameters were then
      used to generate calculated effluent BTC for comparison with observed effluent
      BTC for the same soil columns. Time moments of the calculated and observed BTC
      were calculated to quantitatively evaluate the calculated BTC. Overall, the RM
      BTC obtained from TDR were similar to the RM BTC obtained from effluent data. The
      TDR-determined parameters corresponded well to the parameters obtained from the
      effluent data, although they were not within the 95% confidence intervals.
      Correlation coefficients between the parameters obtained from TDR and from
      effluent data for the immobile water fraction (theta im/theta), mass exchange
      coefficient (alpha), and dispersion coefficient (Dm) were 0.95, 0.95, and 0.99,
      respectively. For three of the four soil cores, theta im/theta ranged from 0.42
      to 0.82, indicating considerable preferential flow. The TDR-calculated effluent
      BTC also were similar to the observed effluent BTC having an average coefficient
      of determination of 0.94. Time moments obtained from calculated BTC were
      representative of those obtained from observed BTC. The vertical TDR probe method
      was simple and minimally destructive and provided representative preferential
      flow properties that enabled the characterization of solute transport in soil.

PMID- 11588823
TI  - Mineralogical compositions of aquifer matrix as necessary initial conditions in
      reactive contaminant transport models.
AB  - Mineralogical compositions and their spatial distributions are important initial
      conditions for reactive transport modeling. However, popular Kd-based "reactive"
      transport models only require contaminant concentrations in the pore fluids as
      initial conditions, and minerals implicitly represent infinite sources and sinks
      in these models. That situation results in a general neglect of mineralogical
      characterization in site investigations. This study uses a coupled multi
      component reactive mass transport model to predict the natural attenuation of a
      ground water plume at a uranium mill tailings site in western USA. Numerous
      ground water geochemistry data are available at this site, but mineralogical data
      are sketchy. Even given the well-defined pore fluid chemistry, variations of
      secondary mineral species and mineral abundances in the aquifer resulted in
      significantly different modeling outcomes. Results show that the amount of
      calcite in the aquifer determines the distances of plume migration. The possible
      presence of jurbanite, an aluminum sulfate phase, can store acidity temporarily
      but cause more severe contamination on a later date. The surfaces of iron
      oxyhydroxides can store significant amounts of sulfate and protons and serve as a
      second source for prolonged contamination. These simulations under field
      conditions illustrate that mineralogical compositions are an essential
      requirement for accurate prediction of contaminant fate and transport.

PMID- 11588824
TI  - Transport and fate of organic wastes in groundwater at the Stringfellow hazardous
      waste disposal site, southern California.
AB  - In January 1999, wastewater influent and effluent from the pretreatment plant at
      the Stringfellow hazardous waste disposal site were sampled along with
      groundwater at six locations along the groundwater contaminant plume. The
      objectives of this sampling and study were to identify at the compound class
      level the unidentified 40-60% of wastewater organic contaminants, and to
      determine what organic compound classes were being removed by the wastewater
      pretreatment plant, and what organic compound classes persisted during subsurface
      waste migration. The unidentified organic wastes are primarily chlorinated
      aromatic sulfonic acids derived from wastes from DDT manufacture. Trace amounts
      of EDTA and NTA organic complexing agents were discovered along with carboxylate
      metabolites of the common alkylphenolpolyethoxylate plasticizers and nonionic
      surfactants. The wastewater pretreatment plant removed most of the aromatic
      chlorinated sulfonic acids that have hydrophobic neutral properties, but the p
      chlorobenzene-sulfonic acid which is the primary waste constituent passed through
      the pretreatment plant and was discharged in the treated wastewaters transported
      to an industrial sewer. During migration in groundwater, p-chlorobenzenesulfonic
      acid is removed by natural remediation processes. Wastewater organic contaminants
      have decreased 3- to 45-fold in the groundwater from 1985 to 1999 as a result of
      site remediation and natural remediation processes. The chlorinated aromatic
      sulfonic acids with hydrophobic neutral properties persist and have migrated into
      groundwater that underlies the adjacent residential community.

PMID- 11588825
TI  - In situ assessment of microbial sulfate reduction in a petroleum-contaminated
      aquifer using push-pull tests and stable sulfur isotope analyses.
AB  - Anaerobic microbial activities such as sulfate reduction are important for the
      degradation of petroleum hydrocarbons (PHC) in contaminated aquifers. The
      objective of this study was to evaluate the feasibility of single-well push-pull
      tests in combination with stable sulfur isotope analyses for the in situ
      quantification of microbial sulfate reduction. A series of push-pull tests was
      performed in an existing monitoring well of a PHC-contaminated aquifer in Studen
      (Switzerland). Sulfate transport behavior was evaluated in a first test. In three
      subsequent tests, we injected anoxic test solutions (up to 1000 l), which
      contained 0.5 mM bromide (Br-) as conservative tracer and 1 mM sulfate (SO4(2-))
      as reactant. After an initial incubation period of 42.5 to 67.9 h, up to 1100 l
      of test solution/groundwater mixture was extracted in each test from the same
      location. During the extraction phases, we measured concentrations of relevant
      species including Br-, SO4(2-) and sulfide (S(-II)), as well as stable sulfur
      isotope ratios (delta 34S) of extracted, unconsumed SO4(2-) and extracted S(-II).
      Results indicated sulfate reduction activity in the vicinity of the test well.
      Computed first-order rate coefficients for sulfate reduction ranged from 0.043 +/
      0.013 to 0.130 +/- 0.015 day-1. Isotope enrichment factors (epsilon) computed
      from sulfur isotope fractionation of extracted, unconsumed SO4(2-) ranged from
      20.2 +/- 5.5@1000 to 22.8 +/- 3.4@1000. Together with observed fractionation in
      extracted S(-II), isotope enrichment factors provided strong evidence for
      microbially mediated sulfate reduction. Thus, push-pull tests combined with
      stable sulfur isotope analyses proved useful for the in situ quantification of
      microbial sulfate reduction in a PHC-contaminated aquifer.

PMID- 11588826
TI  - One-dimensional simulation of solute transfer in saturated-unsaturated porous
      media using the discontinuous finite elements method.
AB  - A one-dimensional transport model for simulating water flow and solute transport
      in homogeneous-heterogeneous, saturated-unsaturated porous media is presented.
      The model is composed of a combination of accurate numerical algorithms for
      solving the nonlinear Richard's and advection-dispersion equations (ADE). The
      mixed form of Richard's equation is solved using a standard finite element method
      (FEM) with primary variable switching. The transport equation is solved using
      operator splitting, with the discontinuous finite element method (DFE) for
      discretization of the advective term. A slope limiting procedure for DFE avoids
      numerical instabilities but creates very limited numerical dispersion for high
      Peclet numbers. An implicit finite differences scheme (FD) is used for the
      dispersive term. The unsaturated flow and transport model (Wamos-T) is applied to
      a variety of rigorous problems including transient flow, heterogeneous medium and
      abrupt variations of velocity in magnitude and direction due to time-varying
      boundary conditions. It produces accurate and mass-conservative solutions for a
      very large range of grid Peclet numbers. The Wamos-T model is a good and robust
      alternative for the simulation of mass transport in unsaturated domain.

PMID- 11588827
TI  - On the hydro-dispersive equivalence between multi-layered mineral barriers.
AB  - In the context of municipal solid waste and hazardous waste disposal, the notion
      of "equivalence" between different barrier designs appears in regulatory
      documents from several industrialized countries. While in the past, equivalence
      has been thought of mainly in terms of contaminant travel times, in recent years
      it has been defined more in terms of the magnitude of a disposal site's potential
      impact on groundwater resources. This paper presents some original analytical
      solutions to the problem of contaminant migration through a multi-layered mineral
      barrier. The solutions account for the two major mechanisms of subsurface
      contaminant migration, namely, advection and diffusion-dispersion. An example
      application using the proposed solutions and a numerical model illustrates how
      one multi-layered mineral barrier can be considered superior to another from a
      strictly hydro-dispersive viewpoint. The influence of partial saturation of the
      mineral barrier is investigated using a numerical solution to the Richards
      equation for unsaturated flow. It is emphasized that conclusions relative to the
      superiority of one multi-layered barrier, with respect to another, should not
      only consider hydro-dispersive aspects, but also other processes such as the
      mechanical and chemical evolutions of the different barrier components. Although
      such phenomena are poorly addressed by existing models, failure to take them into
      account, at least in a qualitative fashion, may lead to unconservative
      conclusions with respect to barrier equivalence.

PMID- 11588828
TI  - Influence of substrate exposure history on biodegradation in a porous medium.
AB  - This study investigates the influence of fluctuating toluene concentrations on
      aerobic toluene degradation in a sandy porous medium colonized with Ralstonia
      pickettii PKO1. Column effluent toluene concentrations were found to increase
      after a temporary decrease in influent toluene concentration. Subsequent
      examination of the spatial gradient of toluene degradative activity in the column
      suggested that the observed increase in effluent toluene concentrations was
      attributable to an adverse effect of toluene limitation on the biodegradative
      activity of attached cells. The traditional Michaelis-Menten-type biodegradation
      equation associated with batch-measured Vmax (2.26 mg toluene/mg living cell/day)
      and KS (1.20 mg toluene/1) of nonstarved cells was unable to predict the observed
      toluene breakthrough behavior when the column had been previously exposed to no
      toluene conditions. An alternative modeling approach was developed based upon the
      assumptions that (i) degradative activity was completely deactivated within the
      no-toluene exposure period (53.5 h) and (ii) a lag-phase was present prior to the
      subsequent reactivation of degradative activity in previously toluene-starved
      cells. These assumptions were independently verified by batch microbial
      investigations, and the modified model provided a good fit to the same observed
      toluene breakthrough curve. Application of single lag-time and threshold
      concentration values, however, failed to predict observed toluene breakthrough
      under different toluene exposure conditions. Results of this experimental and
      modeling investigation suggested that substrate exposure history, including the
      length of the starvation period and the level of substrate concentration,
      affected the induction of biodegradation in the porous medium.

PMID- 11588829
TI  - Tritium and 36Cl as constraints on fast fracture flow and percolation flux in the
      unsaturated zone at Yucca Mountain.
AB  - An analysis of tritium and 36Cl data collected at Yucca Mountain, Nevada suggests
      that fracture flow may occur at high velocities through the thick unsaturated
      zone. The mechanisms and extent of this "fast flow" in fractures at Yucca
      Mountain are investigated with data analysis, mixing models and several one
      dimensional modeling scenarios. The model results and data analysis provide
      evidence substantiating the weeps model [Gauthier, J.H., Wilson, M.L., Lauffer,
      F.C., 1992. Proceedings of the Third Annual International High-level Radioactive
      Waste Management Conference, vol. 1, Las Vegas, NV. American Nuclear Society, La
      Grange Park, IL, pp. 891-989] and suggest that fast flow in fractures with
      minimal fracture-matrix interaction may comprise a substantial proportion of the
      total infiltration through Yucca Mountain. Mixing calculations suggest that bomb
      pulse tritium measurements, in general, represent the tail end of travel times
      for thermonuclear-test-era (bomb-pulse) infiltration. The data analysis shows
      that bomb-pulse tritium and 36Cl measurements are correlated with discrete
      features such as horizontal fractures and areas where lateral flow may occur. The
      results presented here imply that fast flow in fractures may be ubiquitous at
      Yucca Mountain, occurring when transient infiltration (storms) generates flow in
      the connected fracture network.

PMID- 11588830
TI  - Evaluation of certain food additives and contaminants.
AB  - This report represents the conclusions of a Joint FAO/WHO Expert Committee
      convened to evaluate the safety of various food additives and contaminants, with
      a view to recommending Acceptable Daily Intakes (ADIs) and tolerable intakes,
      respectively, and to prepare specifications for the identity and purity of food
      additives. The first part of the report contains a general discussion of the
      principles governing the toxicological evaluation of food additives and
      contaminants (including flavouring agents), and the establishment and revision of
      specifications. A summary follows of the Committee's evaluations of toxicological
      data on various specific food additives (furfural, paprika oleoresin, caramel
      colour II, cochineal extract, carmines, aspartame-acesulfame salt, D-tagatose,
      benzoyl peroxide, nitrous oxide, stearyl tartrate and trehalose), flavouring
      agents and contaminants (cadmium and tin), and of intake data on calcium from
      calcium salts of food additives. Annexed to the report are tables summarizing the
      Committee's recommendations for ADIs of the food additives and tolerable intakes
      of the contaminants considered, changes in the status of specifications of these
      food additives and specific flavouring agents, and further information required
      or desired.

PMID- 11588831
TI  - New insights and methodologies are needed to solve the many epidemiologic enigmas
      of prostate cancer.

PMID- 11588832
TI  - Role of phytochemicals in prevention and treatment of prostate cancer.

PMID- 11588833
TI  - Tea and prostate cancer.

PMID- 11588834
TI  - Alcohol and prostate cancer.

PMID- 11588835
TI  - Smoking and prostate cancer.

PMID- 11588836
TI  - Body size and prostate cancer.

PMID- 11588837
TI  - Does physical activity play a role in the prevention of prostate cancer?

PMID- 11588838
TI  - Occupation and prostate cancer.

PMID- 11588839
TI  - Natural history of prostate cancer--epidemiologic considerations.
AB  - Multicentricity, heterogeneity, and sampling error complicate the study of the
      natural history of prostate cancer. Carcinomas previously termed "latent" are
      probably similar to those detected clinically. The diagnosis of carcinoma is only
      made following biopsy and histologic confirmation. Estimates of grade and stage
      made at the time of detection are prone to sampling error and are likely to
      change following examination of radical prostatectomy specimens. In regions with
      lower life expectancies, the problem of prostate cancer becomes a lower priority
      due to its association with aging. Access to care, numbers of medical facilities,
      and differing public health priorities make international rates difficult to
      compare. However, in view of the high worldwide prevalence of the disease,
      further epidemiologic studies of prostate cancer are warranted.

PMID- 11588840
TI  - Sexual behavior and evidence for an infectious cause of prostate cancer.

PMID- 11588841
TI  - Benign prostatic hyperplasia and prostate cancer.

PMID- 11588842
TI  - Medical history and etiology of prostate cancer.

PMID- 11588843
TI  - Gene-environment interrelations in prostate cancer.

PMID- 11588844
TI  - Potential agents for prostate cancer chemoprevention.

PMID- 11588845
TI  - Prostate cancer early detection: a clinical perspective.

PMID- 11588846
TI  - Impact of screening on incidence and mortality of prostate cancer in the United
      States.
AB  - The potential confounding influence of changing treatment patterns and
      misattribution bias make a definitive conclusion about the link between PSA
      screening and mortality rates tentative at best. At least some of the mortality
      decline since 1991 appears likely to be due to screening, but the precise
      magnitude of the screening effect is difficult to estimate. The possible
      reduction in mortality due to screening, while uncertain, must be weighed against
      the substantial decrements in treatment-specific health outcomes (32-34) among
      men treated for clinically localized tumors typically detected by screening.
      Population data and ongoing screening trials in the United States and Europe (24,
      35) will be complementary in the final determination of the relative contribution
      of the impact of screening versus other causes on recent mortality trends.

PMID- 11588847
TI  - Prostate cancer research in the post-genome era.

PMID- 11588848
TI  - Familial prostate cancer.

PMID- 11588849
TI  - A glimpse into the future.

PMID- 11588851
TI  - Trends and patterns of prostate cancer: what do they suggest?

PMID- 11588850
TI  - Molecular epidemiology of hormone-metabolic loci in prostate cancer.

PMID- 11588852
TI  - Risk of prostate cancer in relation to polymorphisms of metabolic genes.
AB  - The study of associations between genetic polymorphisms of metabolic enzymes and
      prostate cancer risk can provide insight into the potential etiologic role of
      xenobiotics in prostate cancer development. To date there is little evidence that
      the incidence of prostate cancer is influenced by any of the genetic
      polymorphisms described above. However, the number of subjects studied generally
      has been small, so it would be premature to conclude that the substances
      metabolized by enzymes encoded by these candidate genes are not of carcinogenic
      importance, or to conclude that the polymorphisms of these genes do not play a
      role in prostate cancer susceptibility. Larger-scale studies of these and other
      genes, such as genes that repair cellular damage and regulate cell growth, are
      needed. Since gene-gene and gene-environment interactions may contribute to
      cancer risk, it would be desirable to conduct studies in which both biomarkers
      (or other measures) of exposure and polymorphisms of multiple genes are examined.

PMID- 11588853
TI  - Oncogenes and tumor suppressor genes in prostate cancer.

PMID- 11588854
TI  - Hormones and prostate cancer: what's next?
AB  - In summary, the hormonal hypothesis remains one of the most important hypotheses
      in prostate cancer etiology. Although epidemiologic data regarding the role of
      hormones are still inconclusive, there are many intriguing leads. Armed with more
      complete methodological data, state-of-the-art hormone assays, sound
      epidemiologic design, and a more thorough analytical approach, a new generation
      of studies should yield critical data and insights to help clarify further the
      role of hormones in prostate cancer. These new studies may determine ultimately
      whether racial/ethnic differences in hormonal levels and in genetic
      susceptibility to hormone-metabolizing genes can help explain the very large
      racial/ethnic differences in prostate cancer risk.

PMID- 11588855
TI  - Insulin-like growth factors and prostate cancer.

PMID- 11588856
TI  - Peptide growth factors as biomarkers of prostate cancer risk.

PMID- 11588857
TI  - Fat, meat, and prostate cancer.

PMID- 11588858
TI  - Vegetables, fruits, associated micronutrients, and risk of prostate cancer.

PMID- 11588859
TI  - Dairy products, calcium, and vitamin D and risk of prostate cancer.

PMID- 11588860
TI  - Selenium, zinc, and prostate cancer.

PMID- 11588861
TI  - Data trends. Cost and price pressures continue to plague healthcare providers.

PMID- 11588862
TI  - Sharing contrasting experiences at the U.S./U.K Exchange.

PMID- 11588863
TI  - Talent management nurtures future healthcare leaders.

PMID- 11588864
TI  - The disappearing budget surplus.

PMID- 11588865
TI  - Balitz: providing a continuum of care is our commitment.

PMID- 11588866
TI  - HIPAA compliance readiness assessment: a case study.
AB  - Centura Health, a faith-based, not-for-profit IDS headquartered in Denver,
      Colorado, recently undertook a rapid assessment to determine its readiness to
      comply with the standards mandated by the Health Insurance Portability and
      Accountability Act (HIPAA) of 1996. The assessment process consisted of a
      business-impact assessment, compilation of results, a gap analysis, and a
      preliminary business case. The business-impact assessment involved a series of
      interviews. For the business case, results of the business-impact assessment were
      compared with the related HIPAA standard to determine the current level of
      compliance and develop an action plan, for approval by the project steering
      committee, to correct deficiencies. The HIPAA readiness assessment uncovered
      numerous areas in which Centura needed to implement changes, particularly with
      respect to ensuring the security and privacy of patients' paper records.

PMID- 11588867
TI  - Calculating five types of typical underpayments.
AB  - Underpayments to providers under their payer agreements are a cause of many
      thousands of dollars in lost revenue. Providers should devise a plan to make
      certain that payments made to them are accurate, on time, and adhere to other
      contractual obligations. The importance of developing and implementing such a
      plan is substantiated by the fact that nearly 100 percent of a provider's
      commercial business is under contract. As a starting point, providers may wish to
      focus on five common types of underpayments: underfunding due to late payments;
      fee-schedule changes that are contractually disallowed; miscalculation of
      performance-based bonuses and errors in risk-payment reconciliations;
      inappropriate denials or inappropriate downcoding of claims; and non-payments.
      The successful execution of a plan to identify and resolve problems and recover
      payments owed relies on the provider's ability to document and prove that payment
      is due.

PMID- 11588868
TI  - Phase I Stark II regulations provide some flexibility.
AB  - The Centers for Medicare and Medicaid Services (CMS--formerly HCFA) issued Phase
      I regulations of Stark II in January 2001. The Stark II final rule prohibits
      physicians from referring Medicare patients for designated health services (DHS)
      to entities with which the physicians or their immediate family members have a
      financial relationship. A financial relationship can be either an ownership
      interest or a compensation arrangement, and can be direct or indirect. The law
      provides a variety of sanctions, including denial or refund of payment and civil
      penalties. The final rule generally permits physicians to make referrals to
      entities with which they have a compensation relationship, as long as the
      compensation paid to the physician is no more than would be paid to someone who
      provided the same services but was not in a position to generate business for the
      entity. The final rule is substantially different from the January 1998 proposed
      rule. As a result, physicians who refer patients to entities for DHS need to
      ensure that the referrals do not trigger Stark II prohibitions. To avoid
      unknowingly violating the law, healthcare providers need to understand what
      constitutes an entity, how CMS views referrals, and what is and is not a DHS.

PMID- 11588869
TI  - The final Stark II rule: implications for hospital-physician arrangements.
AB  - Effective January 4, 2002, the final Stark II rule gives hospitals and health
      systems greater flexibility in structuring compensation arrangements with
      physicians and physician-owned entities, including more flexibility in
      structuring employment compensation and providing medical staff perquisites.
      Further, certain hospital-physician joint ventures are allowed under the final
      rule. The final rule creates new opportunities for hospitals, but because Stark
      II remains highly technical and violations can result in potentially substantial
      financial liability, financial arrangements with physicians should be structured
      very carefully and reviewed periodically for compliance.

PMID- 11588870
TI  - Final inpatient rehabilitation PPS rule improves on proposed rule.
AB  - On August 7, 2001, the Centers for Medicare and Medicaid Services (CMS--formerly
      HCFA) released the final rule for a new prospective payment system (PPS) for
      inpatient rehabilitation services describing the process that must be used to
      receive payment for such services provided to Medicare beneficiaries. The process
      consists of five steps: First, a clinician performs assessments of the patient
      upon admission and at discharge. Second, the patient is classified into a case
      mix group (CMG) with an assigned relative-value weight within that CMG. Third,
      the Federal prospective payment rate is determined by multiplying the relative
      value weight by an annually updated, budget-neutral conversion factor. Fourth,
      the Federal prospective payment rate is adjusted to account for facility-specific
      factors. Finally, the facility-adjusted payment rate may be adjusted for case
      specific factors. The final rule eliminates three deficiencies in the proposed
      rule by providing increased payment for treating any comorbidities documented
      prior to the second day before discharge, providing more appropriate payment for
      transfer cases, and minimizing the paperwork associated with patient assessment.

PMID- 11588871
TI  - Court orders CMS to correct DSH payments.

PMID- 11588872
TI  - Defined-benefit coverage creates new PFS challenges.

PMID- 11588873
TI  - Realizing HIPAA benefits requires organizational change.

PMID- 11588874
TI  - The VNA of Texas. Preserving the best from the past and providing leadership for
      the future.
AB  - What makes the VNA of Texas so special? After researching these questions for the
      better part of eight months, the author has concluded that there are seven
      reasons why the VNA of Texas is regarded as the home care agency that
      international experts wish to model.

PMID- 11588875
TI  - Diversity of home care services: some things old, some things new.
AB  - This article describes the results of a NAHC survey on the 101 services that home
      care agencies provide. Some agency programs are reinvented services from earlier
      decades, and others are brand new, creative offerings. Some, if not all, are
      bound to spark your interest.

PMID- 11588876
TI  - Expressive puppetry in hospice care.
AB  - As treatments for cancers and other illnesses continue to improve, hospices must
      develop their programs to serve those with chronic illnesses in order to continue
      to be relevant in end-of-life care. One hospice has found a modality, called
      Expressive Puppetry, to improve the quality of life for many dementia patients.

PMID- 11588877
TI  - The self-pay personal assistance market: make it your business.
AB  - To be successful in reaching the self-pay market, providers must take a variety
      of steps, including expanding their service capability, developing an effective
      marketing strategy, and raising capital to finance service expansion costs.

PMID- 11588878
TI  - Creating a new market niche: family caregiver training.
AB  - Home care agencies, recognizing the important part that the family caregiver
      plays in their new operating plans, are incorporating family caregivers in a way
      that allows everyone to benefit.

PMID- 11588879
TI  - Adopt-a-residence: a new nursing opportunity.
AB  - Promoting successful community living by strengthening collaboration between
      building residents, tenant leadership, building management, and the home care
      agency is the goal of this innovative Adopt-A-Residence program.

PMID- 11588880
TI  - Hospice F.O.R.U.M. Hospice care saves Medicare dollars by reducing
      hospitalization.

PMID- 11588881
TI  - HCAAA Update. Caregiving.

PMID- 11588882
TI  - Imagine the future ... imagine benchmarking.

PMID- 11588884
TI  - Modern home care means a changed role for Congress and federal regulators.

PMID- 11588883
TI  - Beginning the home care odyssey.
AB  - Both prevention and management of chronic diseases have traditionally been what
      home care is all about. It will be more that way in the future. The lengthy list
      of home care services is testament to the fact that long-term home care is
      becoming even more important on the national agenda.

PMID- 11588885
TI  - Home healthcare nurses--why they leave and why they stay.
AB  - This is a second article in a series of two reports on the National Association
      for Home Care's (NAHC) study of nursing recruitment and retention. The first
      article presented the results of the quantitative analysis. This article presents
      results of the qualitative analysis.

PMID- 11588886
TI  - 21 reasons home care pays.

PMID- 11588887
TI  - Home care without Medicare: the patient-pay alternative.
AB  - Home care agencies can develop a robust, patient-paid service. The home care
      community now has an excellent opportunity to develop the largely untapped market
      for privately paid, home-based, long-term care management.

PMID- 11588888
TI  - Using the power of the World Health Organization: the international health
      regulations and the future of international health law.

PMID- 11588889
TI  - Licorice and cancer.
AB  - Licorice root is one of the oldest and most frequently employed botanicals in
      Chinese medicine. In the United States, licorice products are most often used as
      flavoring and sweetening agents in food products. Constituents of licorice
      include triterpenoids, such as glycyrrhizin and its aglycone glycyrrhizic acid,
      various polyphenols, and polysaccharides. A number of pharmaceutical effects of
      licorice are known or suspected (anti-inflammatory, antivirus, antiulcer,
      anticarcinogenesis, and others). Licorice and its derivatives may protect against
      carcinogen-induced DNA damage and may be suppressive agents as well. Glycyrrhizic
      acid is an inhibitor of lipoxygenase and cyclooxygenase, inhibits protein kinase
      C, and downregulates the epidermal growth factor receptor. Licorice polyphenols
      induce apoptosis in cancer cells. These and other activities of licorice are
      reviewed, and a rationale is suggested for combinations of agents in preventive
      clinical trials.

PMID- 11588890
TI  - Resveratrol inhibits intestinal tumorigenesis and modulates host-defense-related
      gene expression in an animal model of human familial adenomatous polyposis.
AB  - We studied the effect of oral administration of resveratrol, a natural
      constituent of grapes, on tumorigenesis in Min mice. Min mice are congenic mice
      genetically predisposed to develop intestinal tumors as a result of a mutation of
      the Apc gene. Resveratrol (0.01% in the drinking water containing 0.4% ethanol)
      was administered for seven weeks to Min mice starting at five weeks of age. The
      control group was fed the same diet and received water containing 0.4% ethanol.
      Resveratrol prevented the formation of colon tumors and reduced the formation of
      small intestinal tumors by 70%. Comparison of the expression of 588 genes in the
      small intestinal mucosa showed that resveratrol downregulated genes that are
      directly involved in cell cycle progression or cell proliferation (cyclins D1 and
      D2, DP-1 transcription factor, and Y-box binding protein). In addition,
      resveratrol upregulated several genes that are involved in the recruitment and
      activation of immune cells (cytotoxic T lymphocyte Ag-4, leukemia inhibitory
      factor receptor, and monocyte chemotactic protein 3) and in the inhibition of the
      carcinogenic process and tumor expansion (tumor susceptibility protein TSG101,
      transforming growth factor-beta, inhibin-beta A subunit, and desmocollin 2). Our
      data highlight the complexity of the events associated with intestinal
      tumorigenesis and the multiplicity of the molecular targets of resveratrol. The
      high potency and efficacy of resveratrol support its use as a chemopreventive
      agent in the management of intestinal carcinogenesis.

PMID- 11588891
TI  - Plant tannins inhibit the induction of aberrant crypt foci and colonic tumors by
      1,2-dimethylhydrazine in mice.
AB  - We have shown that naturally occurring tannins possess antitumor promotion
      activity in mouse skin. In the present investigation, we studied the ability of a
      hydrolyzable tannin, gallotannin (GT), and a condensed tannin extracted from red
      alder (RA) bark to inhibit 1,2-dimethylhydrazine (DMH)-induced colonic aberrant
      crypt foci (ACF) and tumors in Balb/c mice. In addition, we determined the
      ability of GT to inhibit the proliferation and to induce apoptosis in a human
      colon cancer cell line (T-84). Mice were given tannins by intraperitoneal
      injections, by gavage, or in drinking water before treatment with DMH for 24
      weeks. Alternatively, mice were given tannins by intraperitoneal injection or
      gavage for only 2 weeks before DMH administration, then tannin administration was
      discontinued and mice were treated with DMH for 24 weeks. The multiplicity, size,
      and distribution of ACF and tumors were significantly inhibited by GT and RA in
      the above treatment regimens. The most effective treatments included GT by
      gavage, RA bark extract by intraperitoneal injection, and either tannin dissolved
      in drinking water. Extent of inhibition of ACF and tumors was gender independent.
      In cell culture experiments, GT treatment for three days inhibited the growth of
      T-84 cells, with a concentration resulting in half-maximal inhibition estimated
      to be 20 micrograms/ml. The treatment was not cytotoxic to cells at 1-40
      micrograms/ml. Interestingly, at 10 micrograms/ml, GT induced apoptosis in T-84
      cells as determined by the Hoechst DNA staining technique. Collectively, these
      findings support a potential role for tannins as chemopreventive agents against
      colon cancer.

PMID- 11588892
TI  - Monoclonal antibody-directed analysis of benzo[a]pyrene metabolism in rat liver
      and extrahepatic tissues: effect of propyl and octyl gallate.
AB  - Monoclonal antibody (MAb) 1-7-1 against 3-methylcholanthrene (MC)-induced forms
      of cytochrome P-450 (CYP) was used to characterize benzo[a]pyrene (B[a]P)
      metabolism in rat liver and extrahepatic tissues and its modulation by phenolic
      antioxidants, propyl and octyl gallates. Male Wistar rats were treated with these
      food additives (50 mg/kg body wt i.p.) twice weekly for 14 days alone or in
      combination with MC. Immunochemical inhibition of aryl hydrocarbon hydroxylase
      (AHH) and [14C]B[a]P metabolism (analyzed by high-performance liquid
      chromatography) were measured in liver, kidney, and lung microsomes. Organ
      specific changes in levels of MAb-mediated inhibition of microsomal metabolism of
      B[a]P were observed. In liver microsomes from untreated rats, AHH was not
      affected by MAb, but in kidney and lung, there was 70% and 50% inhibition,
      respectively. In MC-treated rats, MAb reduced AHH activity by 43% in liver.
      Kidney and lung AHH was inhibited up to 80% by this MAb. Formation of B[a]P
      metabolites in MC-induced microsomes from liver and kidney was affected by MAb in
      a similar way. In lung, the total metabolism was inhibited by 50% by MAb
      treatment, but significant differences in inhibition of individual metabolites
      were observed. Treatment with propyl or octyl gallate alone had no effect on MAb
      inhibition of AHH activity in liver and lung but decreased the level of
      inhibition in kidney. Combined treatment with MC and propyl or octyl gallate
      slightly reduced the effect of MAb on AHH activity in liver and significantly
      reduced the level of inhibition in kidney but did not affect AHH activity in
      lung. The same treatment regimen dramatically reduced MAb inhibition of B[a]P
      metabolism in kidney but had no effect on B[a]P metabolite formation in liver.
      Inhibition by MAb of renal 3-hydroxy-B[a]P, 7,8-B[a]P-dihydrodiol, and 1,6
      quinone-B[a]P was the most affected. In lung, treatment with gallates affected
      only formation of 7,8-B[a]P-dihydrodiol. These results suggest that treatment
      with gallates affects the CYP 1A and may change the CYP isozyme composition and,
      thus, alter the tissues' susceptibility to tumor induction by B[a]P.

PMID- 11588893
TI  - Dietary supplement use in the Prostate Cancer Prevention Trial: implications for
      prevention trials.
AB  - Nutrients included in commonly used dietary supplements, such as vitamins C and
      E, may affect cancer risk. To better understand how supplement use may affect the
      interpretation of cancer prevention trials, we examined dietary supplement use
      among participants in the Prostate Cancer Prevention Trial, a double-blind,
      placebo-controlled trial of the drug finasteride (Proscar) for the primary
      prevention of prostate cancer. Of 15,387 men who completed food frequency
      questionnaires and dietary supplement questionnaires, 44.3% used a multivitamin,
      35% used single supplements of vitamin C or E, and 10-15% used antioxidant
      mixtures or single supplements of vitamins A and D, zinc, or beta-carotene at
      least three times per week. The strongest correlates of supplement use were
      higher education and lower body mass index (p < 0.001), and whites and Asians
      were more likely to use multivitamins and single supplements of vitamins C and E
      than were blacks and Hispanics. Supplement users obtained 87% of their total
      daily vitamin E intake, 61-64% of vitamins A, C, and D, and about half of beta
      carotene, folate, and zinc from supplements. Because supplements, especially
      antioxidants, may confer independent cancer-preventive effects, analytic models
      of study findings should include exposure measurement of dietary supplements with
      appropriate tests for interaction. Our results can be generalized to similar
      chemoprevention trials.

PMID- 11588894
TI  - Effect of the molar ratio of branched-chain to aromatic amino acids on growth and
      albumin mRNA expression of human liver cancer cell lines in a serum-free medium.
AB  - Supplementation of branched-chain amino acids (BCAAs) is often used for the
      treatment of hepatic encephalopathy and low albuminemia in Japan. In this
      scenario, although many cases are complicated with hepatocellular carcinoma in
      chronic viral infection, the effect of BCAA levels on hepatocellular carcinoma
      cells remains unclear. We investigated the effect of the molar ratios of BCAAs to
      aromatic amino acids (AAAs) on the growth and albumin mRNA expression of cultured
      human liver cancer cell lines, HCC-M, HCC-T, PLC/PRF/5, and Hep G2. To exclude
      the effect of fetal serum in culture media on modification of the growth and
      albumin transcription of cell lines, we used a synthetic serum-free medium. We
      found that an increase in the molar ratio of BCAAs to AAAs reduced the growth of
      Hep G2 cells, and it increased albumin mRNA expression in this cell line at a
      molar ratio of 0.1-10. These results suggest that the molar ratio of BCAAs to
      AAAs affect the growth and mRNA expression of some liver cancer cells, and
      supplementation of BCAAs may at least be beneficial to patients with cirrhosis,
      even complicated with liver cancer.

PMID- 11588895
TI  - Soybean saponins inhibit cell proliferation by suppressing PKC activation and
      induce differentiation of HT-29 human colon adenocarcinoma cells.
AB  - Soybeans are major dietary sources of saponins, which have been suggested as
      possible anticarcinogens. This study was performed to determine the effect of
      soybean saponins on cell proliferation, differentiation, and apoptosis in human
      colon cancer cells. HT-29 cells were incubated in various concentrations of
      saponins for 24, 48, and 72 hours. Cell growth and whole cell protein kinase C
      (PKC) activity were determined. Alkaline phosphatase activity and
      carcinoembryonic antigen level were measured as markers for cell differentiation.
      Apoptotic cells were quantified. Study results indicated that soybean saponin
      treatment decreased cell growth in a concentration-dependent manner, and pre
      treatment of the cells with saponins significantly suppressed the 12-O
      tetradecanoyl phorbol 13-acetate-stimulated PKC activity. Cells treated with 300
      and 600 ppm of saponins significantly increased alkaline phosphatase activity by
      146% and 242% of the control, respectively. Also, 4-10 times more
      carcinoembryonic antigen was produced in cells treated with saponins. However, at
      all the concentrations used, saponins did not induce apoptosis, although there
      were slight decreases in apoptotic activity in cells treated with 240 and 600 ppm
      of soybean saponins. These results suggest that crude soybean saponin extract
      effectively suppresses PKC activation and induces differentiation, which possibly
      mediate the growth inhibition of tumor cells. Further experiments, including
      preclinical efficacy studies, are required to fully evaluate soybean saponins for
      their chemopreventive properties.

PMID- 11588896
TI  - Apigenin acts on the tumor cell invasion process and regulates protease
      production.
AB  - Apigenin is a widely distributed plant flavonoid and was proposed as an antitumor
      agent. In this study, we investigated the apigenin effects on the protease
      mediated invasiveness in an estrogen-insensitive breast tumor cell line MDA
      MB231. The results show that apigenin at 22.8-45.5 microM (2.5-10 micrograms/ml)
      strongly inhibited, in a dose-dependent manner, tumor cell invasion through
      Matrigel, cell migration, and cell proliferation. We show that apigenin treatment
      from 22.8 microM (2.5 micrograms/ml) led to a partial decrease in urokinase
      plasminogen activator expression and to a total inhibition of phorbol 12
      myristate 13-acetate-induced matrix metalloproteinase-9 secretion. We also
      demonstrate in the apigenin-treated cells a defective adhesion to Matrigel and a
      G2-M cell cycle arrest. Taken together, our results demonstrate that apigenin is
      a pleiotropic effector affecting protease-dependent invasiveness and associated
      processes and proliferation of tumor cells.

PMID- 11588897
TI  - Kiwifruit protects against oxidative DNA damage in human cells and in vitro.
AB  - Antioxidant micronutrients may account for the beneficial effects of fruits on
      human health. A direct demonstration that consumption of fruit decreases
      oxidative DNA damage in human cells would support this hypothesis. Kiwifruit was
      taken as an example of a food with putative antioxidant properties, and its
      effectiveness at decreasing oxidative DNA damage was assessed in ex vivo as well
      as in vitro tests. The comet assay (single-cell gel electrophoresis) was used to
      measure DNA damage in lymphocytes collected during a human supplementation trial
      with a single 0.5-liter drink of kiwifruit juice (with water as a control). The
      comet assay was also modified to assess the antioxidant effect of kiwifruit in
      vitro by measuring the ability of an extract to interfere with oxidative damage
      to DNA induced by H2O2. Ex vivo, consumption of kiwifruit led to an increased
      resistance of DNA to oxidative damage induced by H2O2 in isolated lymphocytes, in
      comparison with lymphocytes collected after a control drink of water. No effect
      was seen on endogenous DNA damage. In vitro, a simple extract of kiwifruit,
      buffered to pH 7, was more effective than a solution of vitamin C (of equivalent
      concentration) at protecting DNA from damage, whereas at the highest
      concentrations tested, neither kiwi extract nor vitamin C had a protective
      effect. We have demonstrated significant antioxidant activity of kiwifruit ex
      vivo and in vitro, not attributable entirely to the vitamin C content of the
      fruit. Our dual approach is appropriate for testing other fruit and vegetable
      products for potential antioxidant effects.

PMID- 11588898
TI  - Intakes of selected nutrients and food groups and risk of ovarian cancer.
AB  - In a hospital-based case-control study, we examined dietary intakes of selected
      nutrients and food groups and ovarian cancer risk among 496 women with primary,
      histologically confirmed epithelial ovarian cancer and 1,425 women with
      nonneoplastic diagnoses, ages 20-87 years, admitted to Roswell Park Cancer
      Institute between 1982 and 1998. Data on diet and other relevant risk factors in
      the few years before admission were collected with a self-administered
      questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated
      by unconditional logistic regression adjusting for age, education, region of
      residence, regularity of menstruation, family history of ovarian cancer, parity,
      age at menarche, oral contraceptive use, and energy intake. Women in the highest
      vs. the lowest quartile of total energy had a weak increase in risk (OR = 1.25,
      95% CI = 0.90-1.73). Significantly reduced risks were associated with higher
      intakes of dietary fiber (OR = 0.57, 95% CI = 0.38-0.87), vitamin A (OR = 0.66,
      95% CI = 0.45-0.98), carotenoid (OR = 0.64, 95% CI = 0.43-0.93), vitamin E (OR =
      0.58, 95% CI = 0.38-0.88), beta-carotene (OR = 0.68, 95% CI = 0.46-0.98), and
      total fruit and vegetable intake (OR = 0.62, 95% CI = 0.42-0.92). Our findings
      suggest that a diet high in plant foods may be important in reducing risk of
      ovarian cancer.

PMID- 11588899
TI  - Coffee and alcohol intake and risk of ovarian cancer: an Italian case-control
      study.
AB  - The relation between coffee and alcohol intake and ovarian cancer risk was
      analyzed in a case-control study conducted in Italy between 1992 and 1999. Cases
      were 1,031 women, aged 18-79 years, with incident, histologically confirmed
      invasive epithelial ovarian cancer, and controls were 2,411 women, aged 17-79
      years, admitted to the hospital for acute nonneoplastic non-hormone-related
      diseases. Coffee intake (mostly espresso and mocha) was not associated with
      ovarian cancer risk, with an odds ratio (OR) of 0.93 [95% confidence interval
      (CI) = 0.69-1.27] in drinkers of > or = 4 cups/day compared with drinkers of < 1
      cup/day. No meaningful relation was observed with cappuccino (OR = 1.06, 95% CI =
      0.85-1.32 for drinkers compared with nondrinkers), decaffeinated coffee (OR =
      0.64, 95% CI 0.42-0.96), and tea intake (OR = 0.90, 95% CI = 0.75-1.08). Total
      alcohol intake was not associated with ovarian cancer risk (OR = 1.09, 95% CI =
      0.76-1.57 in drinkers of > or = 36 g/day compared with never drinkers). No
      relationship was found with wine (OR = 1.03, 95% CI = 0.70-1.50 for > 39 g/day
      compared with never drinkers), beer, amari, grappa, and spirits. No significant
      heterogeneity was found for coffee or total alcohol intake across strata of age,
      education, parity, oral contraceptive use, family history of ovarian/breast
      cancer, body mass index, and calorie intake. This study, based on a large data
      set; provides no support for a causal association between invasive epithelial
      ovarian cancer risk and coffee and alcohol intake.

PMID- 11588900
TI  - Serum 25-hydroxyvitamin D, dietary calcium intake, and distal colorectal adenoma
      risk.
AB  - Vitamin D has recently emerged as a potentially protective agent against
      colorectal neoplasia. We assessed the associations between dietary vitamin D,
      plasma 25-hydroxyvitamin D [25(OH)D], dietary calcium, and colorectal adenomas in
      a large screening sigmoidoscopy-based case-control study in Southern California.
      Because conversion of serum 25(OH)D to serum 1,25-vitamin D is highly regulated
      by serum calcium, we also assessed modification of the 25(OH)D-adenoma
      association by calcium intake. Cases were 473 subjects with a primary adenoma,
      and controls were 507 subjects who had no adenomas at sigmoidoscopy and no
      history of adenomas. Compared with those in the lowest quartile of intake, those
      in the highest quartile of dietary vitamin D had an adjusted odds ratio (OR) of
      0.83 [95% confidence interval (CI) = 0.49-1.41] and those in the highest quartile
      of dietary calcium had an OR of 0.82 (95% CI = 0.49-1.25). There was a suggestion
      that plasma 25(OH)D may be protective in this population (OR for highest vs.
      lowest quartile = 0.74, 95% CI = 0.51-1.09). A significant protective effect of
      25(OH)D was clearly evident only in those with calcium intakes below (OR = 0.40
      for highest vs. lowest quartile, 95% CI = 0.22-0.71, p for trend = 0.005) and
      above (OR = 1.17, 95% CI = 0.69-1.99, p for trend = 0.94) the median calcium
      intake.

PMID- 11588901
TI  - O6-alkylguanines, dietary N-nitroso compounds, and their precursors in gastric
      cancer.
AB  - Several N-nitroso compounds, present in foods and beverages or formed in the
      stomach from their precursors, act as alkylating agents. By using a highly
      reliable technique (high-resolution gas chromatography-mass spectrometry with
      negative-ion chemical ionization and selected ion recording), we measured a
      series of specific O6-alkylguanines in snap-frozen paired stomach tissue samples
      (tumor and noninvolved mucosa) obtained at surgery from 24 gastric cancer
      patients identified in Florence, Italy. Samples of noninvolved mucosa had higher
      levels of total O6-alkylguanines and more frequently detectable levels (54%) than
      tumor samples (29.2%). O6-propylguanine and O6-methylguanine were the single
      adducts most frequently detected in noninvolved mucosa and tumor tissue,
      respectively. Tumor samples showed higher levels of total O6-alkylguanines in
      female patients (p = 0.03) and among those with a diffuse histological type (p =
      0.06) or seronegative for Helicobacter pylori CagA antibodies (p = 0.06). Mean
      dietary nitrate intake was significantly higher in patients with detectable
      levels of adducts in tumor samples (p = 0.03). Estimated intakes of dimethylamine
      and N-nitrosodimethylamine correlated with total levels of O6-alkylguanines in
      noninvolved gastric mucosa. These findings, although based on a small series of
      cases, support a role for N-nitroso compounds from dietary sources in the
      etiology of gastric cancer.

PMID- 11588902
TI  - Energy intake, body mass index, physical activity, and the colorectal adenoma
      carcinoma sequence.
AB  - Little is known about the precise relationship between energy intake, overweight,
      sedentary lifestyle, and steps in the colorectal adenoma-carcinoma pathway. We
      studied these parameters within a case-control study. Patients with adenomas < 10
      mm (n = 154) or > 10 mm (n = 208) were compared with polyp-free controls (n =
      426) for determining factors associated with adenoma formation, i.e., observed
      for small and large adenomas, or with adenoma growth only. Colorectal cancer
      cases (n = 171) were compared with population controls (n = 309) to determine
      factors specific to the final stage, cancer. Exercise reduced the risk of cancer
      [odds ratio (OR) = 0.3, 95% confidence interval (CI) = 0.2-0.5 for high vs. low
      physical activity] but had little influence on adenomas. High energy intake
      increased the risk of cancer [OR for 5th vs. 1st quintile (OR5) = 1.6, 95% CI =
      0.9-2.9, p = 0.02], but not of adenomas. High body mass index (BMI) significantly
      increased the risk of large adenomas (OR5 = 2.1, 95% CI = 1.2-3.5, p = 0.02 and
      OR5 = 1.7, 95% CI = 1.0-3.1, p = 0.25) for large and small adenomas vs. polyp
      free controls. Neither height nor weight nor BMI influenced the risk of cancer.
      Results were unmodified when controlling for dietary risk factors and family
      history. Energy intake, a sedentary lifestyle, and high BMI were independently
      associated with a high risk of cancer itself or large adenomas, which indicates
      an effect on promotion of colorectal tumors. These findings suggest that
      preventive advice regarding these factors should be provided, even late in life,
      to decrease the risk of colorectal cancer.

PMID- 11588903
TI  - Flaxseed consumption influences endogenous hormone concentrations in
      postmenopausal women.
AB  - Lignans, similar in structure to endogenous sex steroid hormones, may act in vivo
      to alter hormone metabolism and subsequent cancer risk. The objective of this
      study was to examine effects of dietary intake of a lignan-rich plant food
      (flaxseed) on serum concentrations of endogenous hormones and binding proteins
      (estrone, estrone sulfate, 17 beta-estradiol, sex hormone-binding globulin,
      progesterone, prolactin, dehydroepiandrosterone sulfate, dehydroepiandrosterone,
      androstenedione, testosterone, and free testosterone) in postmenopausal women.
      This randomized, crossover trial consisted of three seven-week feeding periods,
      during which 28 postmenopausal women, aged 52-82 yr, consumed their habitual
      diets plus 0, 5, or 10 g of ground flaxseed. Serum samples collected during the
      last week of each feeding period were analyzed for serum hormones using standard
      diagnostic kits. The flaxseed diets significantly reduced serum concentrations of
      17 beta-estradiol by 3.26 pg/ml (12.06 pmol/l) and estrone sulfate by 0.09 ng/ml
      (0.42 nmol/l) and increased prolactin by 1.92 micrograms/l (0.05 IU/ml). Serum
      concentrations of androstenedione, estrone, sex hormone-binding globulin,
      progesterone, testosterone, free testosterone, dehydroepiandrosterone, and
      dehydroepiandrosterone sulfate were not altered with flaxseed feeding. In this
      group of postmenopausal women, consuming flaxseed in addition to their habitual
      diets influenced their endogenous hormone metabolism by decreasing serum 17 beta
      estradiol and estrone sulfate and increasing serum prolactin concentrations.

PMID- 11588904
TI  - Effects of dietary sesame seeds on plasma tocopherol levels.
AB  - The tocopherols, the major vitamers of vitamin E, are believed to play a role in
      the prevention of human aging-related diseases such as cancer and heart disease,
      yet little is known concerning determinants of their plasma concentrations.
      Evidence from animal studies suggests that the dietary source of gamma-tocopherol
      can significantly affect plasma levels of this tocopherol as well as its
      functional vitamin E activity. To determine whether plasma levels of tocopherols
      in humans are similarly altered, a study was undertaken in which subjects (n = 9)
      were fed muffins containing equivalent amounts of gamma-tocopherol from sesame
      seeds, walnuts, or soy oil. We observed that consumption of as little as 5 mg of
      gamma-tocopherol per day over a three-day period from sesame seeds, but not from
      walnuts or soy oil, significantly elevated serum gamma-tocopherol levels (19.1%
      increase, p = 0.03) and depressed plasma beta-tocopherol (34% decrease, p =
      0.01). No significant changes in baseline or postintervention plasma levels of
      cholesterol, triglycerides, or carotenoids were seen for any of the intervention
      groups. All subjects consuming sesame seed-containing muffins had detectable
      levels of the sesame lignan sesamolin in their plasma. Consumption of moderate
      amounts of sesame seeds appears to significantly increase plasma gamma-tocopherol
      and alter plasma tocopherol ratios in humans and is consistent with the effects
      of dietary sesame seeds observed in rats leading to elevated plasma gamma
      tocopherol and enhanced vitamin E bioactivity.

PMID- 11588905
TI  - Low frequency of p53 gene mutations in breast cancers of Japanese-American women.
AB  - Differences in frequencies and patterns of somatic p53 gene mutations among
      racially and geographically diverse populations presumably reflect exposure to
      different mutagens or different responses to certain mutagens. On emigration to
      the United States, Japanese women experience, over several generations, a four-
      to fivefold increase in the incidence of breast cancer. To determine whether this
      increased incidence is associated with a change in the frequency and/or type of
      p53 mutation in their tumors, we examined paraffin-embedded samples of primary
      breast cancers from Japanese-American women in Los Angeles County, CA. Mutations
      in exons 5-9 and adjacent intronic regions of the p53 gene were identified and
      confirmed by direct sequencing. Seven mutations, including 5 missense, were
      detected in 44 primary breast carcinomas, a frequency of 16%. There were six
      transitions and one transversion. As expected, overexpression of p53 protein,
      detected by immunohistochemistry, occurred in tumors with missense mutations;
      tumors with nonsense or splice junction mutations had no detectable p53 protein.
      The frequency of p53 gene mutations showed no increase over that previously found
      in breast cancers of native Japanese women. The increased incidence of breast
      cancer in Japanese-American women is likely to be multifactorial in nature and
      warrants further studies.

PMID- 11588906
TI  - Food frequency questionnaire and a screening test.
AB  - We assessed the accuracy of a 141-item food frequency questionnaire as a
      screening test to detect high or low consumption of nutrients associated with
      cancer. Fifty-five men and 58 women participating in two population-based cohort
      studies in Miyagi, Japan, provided four three-day diet records over a one-year
      period and subsequently completed the questionnaire twice with a one-year
      interval. Pearson correlation coefficients between 17 nutrients measured by the
      diet records and the first questionnaire ranged from 0.24 to 0.85 (median 0.43),
      and those between the two questionnaires ranged from 0.47 to 0.91 (median 0.68).
      The sensitivity and specificity of the questionnaire for detecting high-alcohol,
      high-fat, low-calcium, and low-ascorbic acid consumers were 86.7% and 96.7%,
      50.0% and 85.7%, 48.8% and 76.4%, and 61.9% and 70.0%, respectively. Receiver
      operating characteristic curves indicated comparable performance of the
      questionnaire and a three-day diet record, regarded as another screening test.
      The questionnaire performed poorly for other nutrients. The results indicate that
      our questionnaire is reasonably reproducible, comparable with the diet records,
      and useful as a screening test to detect high or low consumers of several
      nutrients associated with cancer for subsequent enrollment in dietary
      intervention trials or dietary counseling.

PMID- 11588907
TI  - Pilot study of a specific dietary supplement in tumor-bearing mice and in stage
      IIIB and IV non-small cell lung cancer patients.
AB  - Previously, a specific dietary supplement, selected vegetables (SV), was found to
      be associated with prolonged survival of stage III and IV non-small cell lung
      cancer (NSCLC) patients. In this study, several anticancer components in SV were
      measured; the anticancer activity of SV was assessed using a lung tumor model,
      line 1 in BALB/c mice. SV was also used in conjunction with conventional
      therapies by stage IIIB and IV NSCLC patients whose survival and clinical
      responses were evaluated. A daily portion (283 g) of SV was found to contain 63
      mg of inositol hexaphosphate, 4.4 mg of daidzein, 2.6 mg of genistein, and 16 mg
      of coumestrol. Mouse food containing 5% SV (wt/wt) was associated with a 53-74%
      inhibition of tumor growth rate. Fourteen of the 18 patients who ingested SV
      daily for 2-46 months were included in the analyses; none showed evidence of
      toxicity. The first lead case remained tumor free for > 133 months; the second
      case showed complete regression of multiple brain lesions after using SV and
      radiotherapy. The median survival time of the remaining 12 patients was 33.5
      months, and one-year survival was > 70%. The median survival time of the 16
      "intent-to-treat" patients (including ineligible patients) was 20 months, and one
      year survival was 55%. The Karnofsky performance status of eligible patients was
      55 +/- 13 at entry but improved to 92 +/- 9 after use of SV for five months or
      longer (p < 0.01). Five patients had stable lesions for 30, 30, 20, 12, and 2
      months; two of them, whose primary tumor was resected, used SV alone and
      demonstrated an objective response of their metastatic tumors. In addition to the
      two lead cases, eight patients had no new metastases after using SV. Three
      patients had complete regression of brain metastases after using radiotherapy and
      SV. In this study, daily ingestion of SV was associated with objective responses,
      prolonged survival, and attenuation of the normal pattern of progression of stage
      IIIB and IV NSCLC. A large randomized phase III clinical trial is needed to
      confirm the results observed in this pilot study.

PMID- 11588908
TI  - Effects of lycopene and Sho-saiko-to on hepatocarcinogenesis in a rat model of
      spontaneous liver cancer.
AB  - The Long-Evans Cinnamon (LEC) rat is a well-characterized model of spontaneous
      hepatocarcinogenesis. It has been shown that dietary administration of lycopene
      or the herbal medicine Sho-saiko-to (TJ-9) has anticarcinogenic activity,
      although the mechanism by which these products protect against carcinogenesis is
      not well known. We investigated the outcome of administration of lycopene and TJ
      9 on the occurrence of hepatic neoplasia in LEC rats. A diet containing 0.005%
      lycopene (originally the product of tomato oleoresin containing 13% lycopene) and
      1% TJ-9 (crude extracts of 7 herbs: bupleurum root, pinellia tuber, scutellaria
      root, jujube fruit, ginseng root, glycyrrhiza root, and ginger rhizome) was
      administered from 6 weeks of age until the rats were sacrificed at 76 weeks of
      age, at which time most of the nontreated animals were known to have
      hepatocellular carcinoma (HCC). Development of HCC in treated groups was analyzed
      histologically by comparison with untreated controls. Glutathione S-transferase
      placental form (GST-P) was analyzed by an immunohistochemical method.
      Concentration of copper, iron, and zinc, which appear to play a role in
      hepatocarcinogenesis in LEC rats, was analyzed. The percent areas of HCC in the
      liver specimens of control, lycopene, and TJ-9 groups were 17.9 +/- 17.1%, 27.2
      +/- 20.8%, and 27.6 +/- 18.4%, respectively. These intergroup differences were
      not significant. The percent area, number of areas, and mean size of area
      staining positively for GST-P revealed no significant differences between the
      groups. The number of GST-P-positive areas within the HCC lesions was greater in
      the TJ-9 group than in the control or lycopene group (p = 0.024 and p = 0.012,
      respectively). The study also demonstrated a lower concentration of iron in
      livers of the lycopene group than the control group (p = 0.019). There were no
      differences in serum alpha-fetoprotein levels or the cumulative survival rates
      between the groups. In conclusion, long-term administration of lycopene or TJ-9
      did not reduce the risk of hepatocarcinogenesis in LEC rats.

PMID- 11588909
TI  - Literature searching and document delivery: organisational issues.
AB  - An overview of financial, staffing and administrative issues regarding online
      literature searching and document supply is given in this article. Online
      literature searching and the requesting of documents have been problematic in the
      past due to costs and lack of information technology. Electronic document
      delivery requires better Internet access but MIME compatible e-mail can be used.
      Institutional issues regarding requests include the question 'who should order?'-
      the end user or intermediary ordering by the institution, and the need for
      trained information professionals within medical institutions. Payment mechanisms
      can be by credit card, institutional subscription, institutional account with the
      supplying library or by voucher system. Organisational Document Supply Networks
      (LoansomeDoc) now exist that have set charges for certain services between
      members or different costs for different member types and with agreed payment
      mechanisms. An area of increasing importance for document delivery (due to
      international treaties) is copyright. If such legislation is not to adversely
      affect information access, professionals must be involved in the creation and
      amendment of such legislation. Finally, a list of references are given many of
      which include internet addresses.

PMID- 11588910
TI  - Research imperialism in Pacific health: the case of Tonga (1966-1997).
AB  - Researches of and among Pacificans have been largely externally initiated, funded
      and controlled. It has become an imperialist tool to colonize, oppress and
      control the aspirations of Pacificans. This case study shows that research
      imperialism thrives in Tonga. Economic and social efficiency can be achieved
      through local initiatives by native researchers. Such an alternative approach
      must replace foreign data prospectors, "mosquito scientists" and "parachute
      consultants". This study provides a rapid assessment methods for monitoring
      research performance among Pacificans.

PMID- 11588911
TI  - Telehealth and outbreak prevention and control: the foundations and advances of
      the Pacific Public Health Surveillance Network.
AB  - The Pacific Public Health Surveillance Network (PPHSN) of which PACNET is now an
      integral part was established in 1996. PACNET is an innovative technical
      communication facility for strategic and high priority disease outbreak detection
      and control. PPHSN consists of National and International agencies, networks and
      institutions involved in Health activities in 22 Pacific island countries. Its
      aim is to improve public health surveillance in the Pacific islands in a
      sustainable way with outbreak alert and response a current priority. This report
      reviews the development of PPHSN, its associated public health Laboratory network
      (LabNeT) and the more recent EpiNet that is a regional investigation and response
      service. Telehealth is also discussed in terms of what services can PPHSN
      currently provide and what improvements can it pursue to actively contribute to
      the dynamic development and welfare of Pacific communities in the twenty first
      century.

PMID- 11588912
TI  - Pacific Health Research Council: health research by and for Pacificans.
AB  - The inaugural meeting of the Pacific Health Research Council (PHRC) was held at
      Sonaisali, Fiji 12-14 Oct 1998. It was attended by representatives of eight
      Pacific Island countries and five Pacific Island institutions. The organisation
      is designed to provide three levels of membership: Pacific Island countries;
      Pacific Island institutions; and individual Pacific Island researchers. An
      executive committee was appointed and given the task with the special objectives:
      to promote and strengthen health research by Pacific people and; to develop
      Pacific people capacity to exert more control and ownership of data generated
      through research. In the past Pacific health research has often been driven by
      external agendas and there is a need to increase the capacity among Pacific
      Island people to conduct action oriented research. An initial collaborative
      project for the PHRC is in the area of injury prevention and control.
      Implementing tasks of the PHRC will require the use of distant consulting and co
      ordination to provide ongoing technical assistance, to manage multi-centre
      activities, and to share ideas and concerns etc. Hence, PHCR will be interested
      in participating in evolving telehealth networks in order to adequately address
      these tasks. In the spirit of cooperation and co-ordination, the PHRC can be
      expected to become actively involved in these emerging developments.

PMID- 11588913
TI  - A method for active surveillance of selected communicable diseases.
AB  - In 1991, an initiative was launched in the Western Pacific Region of WHO to
      eradicate poliomyelitis by the year 2000. Confirmation of eradication requires a
      certification process, in which specific criteria must be met. A hospital-based
      surveillance system was developed. It was sensitive enough to detect, at least
      one case of acute flaccid paralysis (AFP) per 100,000 children under age 15 per
      year, which is considered the "background rate" of AFP. This system was
      instituted in 1997 in most countries in the Pacific, and included measles and
      neonatal tetanus as well as AFP. By mid-1998, 53 hospitals in the Pacific were
      submitting monthly forms indicating whether or not AFP, suspect measles, or
      neonatal tetanus had been seen in the preceding month. Compliance was excellent,
      with over 80% of forms submitted to WHO in 1998, thus meeting the certification
      standard. In 1999 a proposal was made to expand this method, in selected
      countries, to encompass most conditions presenting with acute fever plus rash,
      thus including, for example, cases of rubella and dengue. Important aspects of
      such surveillance include the capacity to confirm diagnoses in the laboratory,
      and to take effective public health action. A coordinated laboratory network had
      been established previously for virological analysis of stool specimens for
      conditions causing AFP, but laboratory support for other conditions is currently
      the responsibility of individual hospitals to arrange.

PMID- 11588914
TI  - Dengue surveillance in the Pacific Islands.
AB  - Adequate monitoring of dengue activity can be achieved using a combination of
      mosquito vector surveillance, fever surveillance, sentinel clinicians and
      laboratory screening. An apparent increase in fever cases or clinically suspected
      DF should prompt a careful clinical and laboratory investigation. If an outbreak
      of dengue is confirmed, health authorities will need to implement emergency
      community-wide control strategies. Laboratories will quickly feel the burden of
      clinical monitoring of cases admitted with DHF/DSS. Surveillance can change to
      clinical case definitions as health workers become familiar with the presenting
      features of DF and DHF/DSS. Criteria for hospital referral and admission must be
      well understood. Routine laboratory and sentinel surveillance may resume as the
      epidemic wanes, and should then continue indefinitely to monitor any resurgence
      of dengue activity.

PMID- 11588915
TI  - Monolingual monologue: regional issues of professional communication from Pacific
      Health Dialog.
AB  - The Pacific Health Dialog (PHD) is a Journal of Community Health and Clinical
      Medicine with a Pacific. focus. A analysis of all nine PHD issues from 1994 to
      1998 was made for origin of author and content. Tally sheets were used to compile
      data from which the tables were constructed. The results showed that of the
      15,000 journals printed 70% were distributed to Pacificans. There were 287 items
      published by 489 authors of which 37% were Pacificans who were also the first or
      only author in 37% (excluding the authors of book reviews, editorials reprints,
      letters and abstracts). The contents of PHD have all been written in English even
      though the policy allows for any major Pacific language. Therefore a monolingual
      journal has emerged in spite of a multilingual policy. There has been minimal
      dialogue or discussion in PHD and not much of the content has been challenged, so
      the papers have become monologues by the authors. Thus we have a monolingual
      monologue. PHD is donor dependent with a hand to mouth existence. Funding covers
      only part of the expenditure and the balance comes from a 'labour of love' from
      many people. Despite this, PHD continues to grow. The development of PHD has
      demonstrated that a participatory media can increase the Pacificans role in
      health information dissemination throughout the Pacific. Many of the Pacific
      authors (73.5%) have never published previously. Since 1994 PHD has come a long
      way and contributed much to pacific based research. It addresses a wide variety
      of topics and problems and not just the need for medical information. PHD has
      become the prototype for regional health communication in terms of participation,
      ownership, development, maintenance and its use of 'labour of love' resources.

PMID- 11588916
TI  - Pacific Island Health Care Project: early experiences with a Web-based
      consultation and referral network.
AB  - The Pacific Island Health Care Project (PIHCP) has in the past provided
      definitive care at the Tripler Army Medical Center (TAMC) for nearly 3000
      patients. To contain costs, increase access, and provide consultative and
      referral services to physicians in the Pacific Basin, a web-based network was
      established in 1997. Four sites in the Western Pacific were provided with a
      desktop computer, digital still and video cameras, flatbed scanners, and
      printers. Consultations with supporting imagery are submitted to TAMC where the
      consults are data-based and dynamically posted on a secure web server. TAMC
      consultants triage and comment on the cases and the educational significance.
      Unnecessary or inappropriate referrals are returned with instructions for local
      care. Cases are formatted to allow rapid response, image review,
      consultant/provider interaction, and peer review. More than 180 consults have
      been submitted from the island nations electronically (30 September 1998) and
      initial experience indicates that the Internet can be easily used as an
      inexpensive store and forward consultation format. There has been an overwhelming
      enthusiasm for this project by all participants and for the first time since the
      inception of the PIHCP, funding was available during the entire fiscal year, with
      tens of thousands of dollars saved.

PMID- 11588917
TI  - The role of the Picasso phone system in distance consultation for remote Pacific
      Islands.
AB  - The U.S. affiliated Pacific Island nations spend an average of over 10% of total
      health budget on off-island referral care to tertiary centers. Tripler Army
      Regional Medical Center (TAMC) has been the major provider of this service for
      many years. Prior to 1995 communication to consultants at TAMC was by long
      distance telephone, fax and regular mail. Connecting to a specialist sometimes
      took hours and clearly a better communication link was needed. The AT&T Picasso
      phone, an instrument the size of a small briefcase was developed to reliably
      transmit still images over the regular phone. Freeze-frame images captured at the
      sending end by a cam recorder were transmitted to a remote receiver unit, where
      they were displayed and stored. A typical medical consultation involved about
      three images, with each transmission over the 28.8 Kbps modem taking about one
      minute. A separate consultation form submitted by fax to TAMC was attached to the
      transferred images. Four Picasso phones were used to test their usefulness in
      linking isolated Pacific islands to a metropolitan medical center. For the first
      time ever, coloured patient images, data, X-rays etc were transmitted with a
      faxed written medical report. The Picasso phone was the spark of the Telemedicine
      development in the US affiliated Pacific islands.

PMID- 11588918
TI  - Telehealth.

PMID- 11588919
TI  - Telemedicine in the Federated States of Micronesia.
AB  - Telemedicine (other than costly long distance telephone and facsimile messages)
      in the Federated States of Micronesia (FSM) started approximately 4 years ago
      with the establishment of Internet access in the State of Yap. A local access,
      for medical use only, via already established trunk lines maintained by
      Continental Airlines was established. It provided a connection to CompuServe at a
      baud rate of 300 bps. FSM TeleCom provided this free service. While this
      connection was slow, it allowed medical staff at Yap State Hospital to send and
      receive text based e-mail regarding patient management. By its use interest was
      generated in both medical and non-medical individuals to develop a commercial
      full scale Internet service. In March 1996, TeleCom became a full scale
      commercial Internet Service Provider in Yap. Rates were reasonable and the
      CompuServe access was phased out. The full scale internet allowed medical
      personnel to engage in telemedicine activities, including email; email
      attachments; the search and retrieval of medical literature; transmission to
      medical specialists of X-rays, ECG's and other images; and real-time
      teleconferencing over the Internet with both audio and video. In addition, to the
      improvement of medical care, this allowed for greater efficiency in arranging
      referral of patients for medical treatment outside of the FSM.

PMID- 11588921
TI  - Telehealth for the new Pacific.

PMID- 11588920
TI  - Teleconsultations in Pohnpei State, Federated States of Micronesia.
AB  - A case report of 6 years old female who sustained a difficult right
      subtronchanteric fracture of the femur is outlined. She was treated successfully,
      with local materials, over the internet with assistance of the orthopaedic
      surgeons at the Tripler Army Medical Center in Honolulu. Pohnpei State spends 10%
      of the health budget in referring patients off-island for tertiary treatments and
      this serves less than 1% of the total population. Before the use of the internet,
      approximately $US1,500 per month was spend on telephone bills, for outside
      consultations. After connection to the internet and the consult webpage,
      particularly at Tripler, this cost was reduced to below $US500 per month. To
      date, fifty consults, via the Internet, have been sent to the TAMC Consult
      Webpage. The introduction of this service has resulted in cost saving in terms of
      referral communication and perhaps avoided unnecessary off island evacuations.
      The difficulties so far have been limitation of on-line access and computer
      illiteracy amongst physicians.

PMID- 11588922
TI  - Telemedicine in Majuro Hospital, Marshall Islands.
AB  - Since March 1998 up to June 2000, telemedicine activities in Marshall Islands
      have mainly been for Referrals to Tripler Army Medical Center (TAMC) in Hawaii.
      The activities are based on a computer which has the Internet connection and
      accessories including a digital camera, flatbed scanner with a transparency
      adapter, color printer, a video printer, ophthalmoscope, otoscope and a video
      Lens, all of which were donated by Project Akamai in Hawaii. Two sessions of
      training were conducted by representatives from Akamai Project and from PBMA at
      the very beginning of the establishment of the unit, to all levels of Health Care
      Providers in Ministry of Health in Majuro. The computer and Internet facility is
      available 24 hours. Since March 1998 to June 2000, there had been 144
      telemedicine consultations to TAMC. Out of a total of 326 off-island referrals
      for the same period, approximately 80 patients have been sent to TAMC using the
      PIHCP/Telemedicine program. This accounts for approximately 25% of total off
      island referrals. This represents a significant reduction in cost. In addition to
      cost reduction the telemedicine unit most important impact is on the health
      providers, especially the physicians working at Majuro Hospital. Availability of
      medical information through internet has helped them to feel less isolated from
      the constantly changing field of medical science.

PMID- 11588923
TI  - Health and telecast: a milestone for Tonga into the 21st century.
AB  - An efficient Telehealth system for Tonga is currently but a dream. The kingdom of
      Tonga consists of 36 inhabited islands occupying 669 kms2 and a population of
      97,784 (1996). There is a referral hospital in the Capital and three other
      district hospitals, 14 peripheral health centres, 32 maternal child health
      clinics and eight general practitioners. Within the kingdom the use of the
      telephone, telegram and some use of fax are the main ways of contact between the
      hospitals and the more remote health centres. Patients needing specialty care not
      available locally are referred, and possibly transferred, to New Zealand from the
      referral hospital in the Capital. There are seldom any communications with other
      health professionals or institutions through telecast. This article details the
      present situation and discusses the perceived advantages and difficulties in
      establishing a functional Telehealth service in Tonga.

PMID- 11588924
TI  - Proposed New Caledonia telemedicine network.
AB  - Healthcare can now be provided from a distance allowing doctors to make a
      diagnosis or give an opinion on possible treatment without meeting the patient
      directly. This requires digital imagery via telehealth which is theoretically
      well suited to New Caledonia's geographic and demographic characteristics. After
      using video-conferencing with mainland France over a period of several months as
      part of a continuing medical training programme, it became clear that a
      telehealth network would improve local health care efficiency and this concept is
      being incorporated into the Territory's overall health policy. A needs assessment
      was conducted to assess the expectations of doctors and this highlights the need
      to develop such a network, as soon as possible. The exact mode of communication
      has not yet been determined and in this article the expressed needs of doctors
      and the proposals with advantages and constraints are discussed in legal,
      ethical, financial, organisational and medical terms.

PMID- 11588925
TI  - Telehealth in the Pacific Islands: a perspective and update from the Fiji School
      of Medicine.
AB  - The Fiji School of Medicine (FSM) has increased participation with
      telehealth/telemedicine in general, and specifically with the Pacific Public
      Health Surveillance Network (PPHSN) and the Western Pacific HealthNet(WPHNet),
      through the establishment of a WPHNet Centralised Triaging Service (CTS). The FSM
      Telehealth/Telemedicine Unit (FSMTU) will oversee the development of the CTS
      which is being closely coordinated with existing clinical consultation services
      provided through Project Aamai and the Tripler Regional Medical Center (TRMC).
      While the WPHNet CTS will initially be concerned with distance clinical
      consultation, the FSM mission encompasses community health and professional
      health education in a wide range of disciplines. Currently, WPHNet only serves
      the jurisdictions of the US-associated Pacific islands but with WPHNet CTS there
      will be an opportunity to include new member jurisdictions that do not have
      political affiliation with the USA. (e.g. Cook Is, Kiribati, Niue, Samoa, Solomon
      Is, Tonga, Vanuatu etc). In addition, although Internet technology is expanding
      rapidly in the region, the capacity for outside communication throughout the
      Pacific is quite varied. Very remote areas may currently only be able to
      communicate by using short wave radio. Others have telephone and/or fax while
      some have E-mail but not full internet capacity. The FSMTU will implement
      mechanisms to field requests through any of these communication avenues and so
      the WPHNet CTS will serve as a proxy for regional healthcare providers that do
      not have internet access.

PMID- 11588926
TI  - Experience and hopes for telehealth in Tokelau.
AB  - The two key factors affecting healthcare in Tokelau are its small population and
      its great isolation. Both of these make telehealth a critical issue for the
      development of health services and it is hard to see how the services can develop
      to a modern standard without a larger component of telemedicine. The Tokelau
      islands consist of three roughly equal atolls usually served by 1-2 doctors who
      deal with all aspects of medical care. There is a small hospital on each atoll
      and each is staffed by a Nurse manager, two staff nurses and some nurse aides.
      There is a need for a communication facility for the nurse on the atoll(s)
      without a doctor to consult with a doctor about medical cases; doctors to consult
      each other; and for doctors to consult outside specialists about the management
      of cases. Distance education for health care staff is another perceived need. The
      current communications systems are still basic and although there is a PeaceSat
      terminal on each atoll it has largely failed to provide the above communication
      needs and most is still done by the costly telephone system. Recently ITC has
      been made a priority for the health department.

PMID- 11588927
TI  - The role of low cost communications in health in the redevelopment of the
      indigenous physician workforce among selected jurisdictions of the US-associated
      Pacific Islands.
AB  - Low cost communications in health are key to the strategic redevelopment of the
      indigenous physician workforce among select countries of the U.S-Associated
      Pacific Islands. In conducting the Pacific Basin Medical Officers Training
      Program (PBMOTP) from 1986-1996, the University of Hawaii established five key
      strategic objectives to train and support physician graduates from the Freely
      Associated States of the Federated States of Micronesia and the Republics of the
      Marshall Islands and Palau. These objectives were to: conduct a basic medical
      education program which graduated 70 physicians; promote regional internship
      training programs; assist in establishing formal postgraduate training
      opportunities; reestablish a regional physician's professional organization; and
      promote both regional and local continuing medical education activities. Inherent
      in the PBMOTP training program was familiarising students with hands on research
      methodologies, use of computers and information systems, and the processes of
      "store and forward" distant medical consulting. This paper documents the regional
      development of expanded access to medical information and distance medical
      communications technology and processes, including CD_Rom, Epiinfo, Picasso
      phone, E-mail, and Website based consult and Medical information search.
      Recently, email and Internet processes have promoted access to and the use of low
      cost communications in health thereby further reducing professional isolation
      among the new physician workforce in Micronesia.

PMID- 11588928
TI  - Distance learning in the public health workplace.
AB  - The Master of Applied Epidemiology (MAE) Program implemented in Canberra to
      produce public health practitioners with specified competencies in the control of
      communicable diseases. Twenty one of the 24 months of training is distance
      learning defined as, 'where the learner is physically remote from the training
      institution'. During this time the trainees are in supervised employment in
      Public Health centres across the country. Here they learn directly from first
      hand experiences in the work place. They return to Canberra for short, intensive
      periods of interactive sessions with their peers and supervisors. Lessons learnt
      from conducting this program are discussed in this article. They include: all
      trainees are not suited to this form of training; the quality of support from the
      field supervisors is highly variable and their role in modelling crucial to the
      trainees performance; demands on the academic staff is high; and the frequency of
      contact between trainee and academic supervisor varies considerably. To date this
      program has made major contributions by enhancing communicable disease
      surveillance and control but it demands intensive resources to sustain, quality
      training, and support. This model of distance learning can be adapted in the
      Pacific both for graduate degree courses and also for continuing education for
      all levels of health professionals.

PMID- 11588929
TI  - Distance education: strategies for maintaining relationships.
AB  - Experience with Australian Aboriginal and Torres Strait Islander students in the
      Bachelor of Applied Health Science (BAppHSc) course suggests that one of the key
      elements for students is the sense of relationship built up through Problem Based
      Learning (PBL). Failure to retain students is more likely to be related to
      personal than academic concerns. The low attrition rate is largely attributed to
      the sense of community and support the course generates. In 1997, the Centre for
      Indigenous Health, Education and Research offered the BAppHSc to rural
      Queensland. Campuses were opened in the Torres Strait and Cairns, with 9 and 5
      students respectively. The course consisted of PBL sessions, fixed resource
      sessions provided by local staff or guest lecturers, video-conferencing and the
      use of videos, or text. Face-to-face contact hours were concentrated into two
      blocks of one and two weeks respectively, plus one day per week. Course materials
      such as journal articles and texts were provided. The nine Torres students and
      three Cairns students completed the first semester. This paper discusses the
      differences between the centres and examines strategies for maintaining the sense
      of relationship in distance education settings. In 1999 applications from other
      remote areas are challenging the model further. Multiple technologies are
      envisaged and discussed. In addition, similar methods are being applied to post
      graduate courses and collaboration with other institutions in the Pacific
      suggested. This would allow cross crediting of such course-work into a range of
      courses and institutions, reducing duplication and increasing options.

PMID- 11588930
TI  - Service-oriented training in public health: a model for enhancing public health
      surveillance in the Pacific.
AB  - There is a need for a coordinated, sustainable, in-service, training programme in
      surveillance and other public health activities. This should be available for all
      levels of health personal throughout the Pacific. The model advocates continuing
      education and in-service training that immediately and directly enhances
      surveillance. Specific educational objectives for surveillance should be based on
      the needs of the work environment while the graduate degree training should
      include broader objectives integrated with established public health training
      courses. It is suggested that the Secretariat of the Pacific community (SPC)
      should provide the leadership by establishing a Centre for Coordinating Service
      oriented Training in Surveillance and invite the University of PNG and the Fiji
      School of Medicine to incorporate training modules in surveillance into their
      degree programmes. Field support should be provided through the senior public
      health practitioners based in public health units and in health agencies
      throughout the region.

PMID- 11588931
TI  - The community in the classroom: designing a distance education community health
      course for nurses in Solomon Islands.
AB  - In 1994 in order to improve educational opportunities for nurses in the Solomon
      Islands and to try the distance learning model as an educational method, the
      Distance Education Programme of the Ministry of Health implemented five post
      basic nursing certificate courses for health workers. This paper focuses on
      issues and experiences in the development of the Community Health course which in
      some ways as the most difficult of the courses to prepare. As in many Pacific
      Island countries, the geographic context of Solomon Islands creates isolated
      working situations for rural health practitioners, with difficult and limited
      communications. Each module in the course consists of a study guide with glossary
      and in-text questions, hand-outs, and an assignment. Videos are available to
      accompany several units and practical teaching aides are also given. Audiotapes
      for teaching sessions are currently being developed. The benefits of the distance
      education model offered in this course are discussed in detail and attention is
      drawn to some of the difficulties encountered. Overall, the outcome of the trial
      of this method has been highly successful.

PMID- 11588932
TI  - Distance nursing education in Micronesia.
AB  - Distance education courses have been offered by the University of Guam for the
      past ten years, however there were no programs developed for the students of the
      region. In 1994, the College of Nursing and Health Sciences began teaching
      courses over PEACESAT (Pan Pacific Education and Communications Experiment by
      Satellite) every semester. The first course was written to serve Palau, the
      Commonwealth of the Marianas, Pohnpei, and the Marshall Islands. These
      jurisdictions have large community colleges. An overview of this program is
      given. In 1997 the courses were extended to include Palau, Yap, Chuuk, Pohnpei,
      Kosrae, and the Marshall islands. The organisational structure and training of
      the site operators and training coordinators is described. Two courses were
      taught in the first year. The first was 'Nutrition for Health Professionals and
      the second Leadership/Management for nurses. These are described, evaluated and
      discussed.

PMID- 11588933
TI  - Fiji School of Medicine Diploma and Masters programmes.
AB  - The new diploma and masters programmes at the FSM have attempted to address the
      problem of designing courses where the teaching resources and trainees may be
      spread over vast distances. The theory component of the courses consists of
      modules designed to be distant taught. The learning philosophy is case based with
      problem solving methodologies. Each of these theoretical modules has final and
      enabling objectives which these underpin the development of the module. Clinical
      case stems are produced. The cases unfold by progressively revealing information.
      Self-assessment pretests help the candidates assess their prior knowledge.
      Readings are either recommended or provided separately. The specific learning
      objectives are detailed in the "tutor guides". These guides allow the module to
      be taught by those not involved in the initial development. The clinical teaching
      is largely achieved by the trainee working with adequate supervision in an
      approved unit in a Pacific Island country. The range and quantity of trainee
      experience is recorded and certified in a personal logbook. Each trainee has an
      allocated day to day supervisor who is responsible for the practical training
      supervision. It is envisaged that as far as possible part of the practical
      training will take place in the home countries of the trainees and that some sub
      specialty training will occur offshore.

PMID- 11588934
TI  - Proposing continuing medical education for the Pacific.
AB  - In response to a request from the Pacific Basin Medical Association and the
      Micronesian Medical Council, the Faculty of Medicine and Health Science at the
      University of Auckland, are developing a distance learning postgraduate programme
      (Masters of Medical Science), for Micronesia. The health care model in the
      Pacific Basin promotes decentralised community-based preventative or clinical
      medicine alongside a high standard of secondary care in the hospital service.
      Medical Practitioners often operate in relative isolation, dealing with a diverse
      range of needs, many of which arise infrequently. The Masters of Medical Science
      Programme emphasises the integration of public health and clinical practice and
      the importance of comprehensive patient, family and community medical care. A key
      focus of the programme is the integration of public health principles into all
      relevant clinical areas, for example: paediatrics papers covers public health
      aspects of care as well as clinical principles in child health. The teaching
      approach will be finalized after establishing an understanding of budgets,
      teaching needs and available communication hardware. It is anticipated the
      programme will utilise a combination of written materials, on-site tutor visits,
      public health and clinical workbooks, audiotapes, videotapes, audiovisual
      conferencing, internet groups, regular tutor response to e-mail requests,
      teleconferencing, telemedicine and interactive internet access and CDs etc. A key
      element to the teaching process is self-directed learning, and a clinical
      workbook will assist in this. Assessment of the course and students are along the
      lines and standards of the University of Auckland.

PMID- 11588935
TI  - Regional training in public health surveillance: how far are we? An SPC
      perspective.
AB  - "Training in applied epidemiology and public health surveillance" is one of the
      five strategies of Pacific Public Health Surveillance Network (PPHSN). It aims to
      develop a regional pool of experts in public health surveillance and response for
      the Pacific Islands. In 1996, the idea of a modular training programme with field
      based components, involving universities, health development agencies and
      professional associations came up. This programme should be accredited by a
      training institution. From 1998 to 2001, SPC made a first move in that direction
      and ran two different series of subregional training sessions in surveillance,
      outbreak investigation and the use of Epi Info 6 software for surveillance
      activities. The overall objective of these training sessions was to build a
      critical mass of health professionals who share a common set of tools and methods
      for public health surveillance. SPC can also provide attachment and hands-on
      field training opportunities for trainees in public health practice. A memorandum
      of understanding was signed between SPC and FSM in 1999. The article suggests the
      areas of future FSM/SPC collaboration in public health surveillance: the
      accreditation of SPC courses by FSM; the addition of a microbiology component;
      the identification of opportunities for field training; and the evaluation and
      harmonisation of the training programme(s).

PMID- 11588936
TI  - The Pacific Islands Internet Project (PIIP) in UNDP, Suva.
AB  - The Pacific Islands Internet Project (PIIP) aims to expose interested parties to
      emerging technologies by creating initial, core national Internet-based
      information systems, and by training users on how to take advantage of such
      systems for sustainable development purposes. PIIP works closely with Small
      Islands Development States Network SIDSNET (http://www.sidsnet.org) and Asia and
      Pacific Development Information Programme APDIP (http://www.apdip.net), both UNDP
      initiatives in this field. The Target Beneficiaries are 15 countries in the sub
      region including Tuvalu, Niue and Tokelau which are still without Internet
      access. PIIP will assist these three countries in their connectivity needs and
      all other countries in other components of the project. Priority is given to the
      smaller island states. There are four components to the project. These are:
      Connectivity (WWW access for Tuvalu, Niue and Tokelau); Training and Awareness
      (through national seminars and training programmes); Internet Applications (in
      areas such as telemedicine, distance education, SIDSnet and other fields in the
      private sector); and Policy (work with telecom and regional organisations in
      facilitating national telecommunications policies that provide a basis for
      development of an ICT strategy). Some of the progress made since the inception of
      PIIP are covered in this paper.

PMID- 11588937
TI  - The Communication Enhancement through Telecommunication (ComET) project.
AB  - The Secretariat of the Pacific Community (SPC) has made strenuous efforts to
      address communication imperatives for its programme delivery to its member
      countries. Initially, it used the Internet to assist in programme delivery.
      However, the low availability and high costs of telecommunications in Noumea and
      Suva hampered these efforts. The use of PACNET (the communications service of the
      Pacific Public Health Surveillance Network) was very successful but restricted by
      communication capabilities and lack of connectivity. In 1998 the capacity was
      limited to 28.8 kilobytes per second (kbps) in Noumea and 1.9 kbps in Suva with
      no possibility of obtaining additional capacity at affordable costs through the
      commercial telecommunications carriers. The ComET project has now installed 7.2
      metre antenna and associated equipment at each of the Secretariat's offices in
      Noumea and Suva. This allows 24 hour per day access to the PAS2 satellite for
      high speed transmission of voice, data and video traffic. Connection to the
      Offratel premises in Nouville via the Celeris high speed backbone operated by OPT
      has linked this to the internet and thereby to member countries and territories,
      and the rest of the world. The ComET project began transmission in March 2000 and
      has addressed communication problems, and thereby improved the SPC's programme
      delivery (examples given in this paper) to it's members at affordable costs
      within the Secretariats existing budget.

PMID- 11588938
TI  - TongaSat: its obligation to Tonga and the Pacific region.
AB  - TongaSat, otherwise known as the Friendly Islands Satellite Communications Ltd.,
      reckons itself as a toddler in the world of telecommunications. But since
      TongaSat has taken Tonga, a small Pacific island nation to the galaxies, it has
      also made it its responsibility to include other Pacific countries in its share
      of the 'glitter'. This short paper is to put TongaSat within the context of the
      Pacific region with the challenges to the rest of the world powers on
      telecommunications.

PMID- 11588939
TI  - Endometrial safety.

PMID- 11588940
TI  - Female pelvic floor dysfunction and estrogen therapy.

PMID- 11588941
TI  - Controversial issues in climacteric medicine II. Hormone replacement therapy and
      cancer. International Menopause Society Expert Workshop. 9-12 June 2001, Opera
      del Duomo, Pisa, Italy.
AB  - Sex steroids are not known to damage DNA directly. They can stimulate or inhibit
      cell proliferation, and thus can modulate tumor developmental progression. Sex
      steroid-related tumors in women are represented by breast cancer and endometrial
      cancer, and a possible relationship exists between sex steroids and both ovarian
      and colon cancer. Among current ERT users or those who stopped use 1-4 years
      previously, the relative risk of having breast cancer diagnosed increases by a
      factor of 1.023 for each year of hormone use. This increase is comparable with
      the effect on breast cancer of delaying menopause, and seems to be largely
      limited to lean women. The breast cancers diagnosed during ERT are more likely to
      contain ER and are less aggressive. Some reports indicate no increase in breast
      cancer mortality in HRT users. Recent data suggest that an estrogen-progestin
      regimen may increase breast cancer risk beyond that associated with estrogen
      alone. However, the effect of progestogens on the breast awaits further
      clarification. ERT/HRT is generally considered to be contraindicated in breast
      cancer patients, as no firm data are yet available from randomized clinical
      trials. Despite the potential risks, ERT/HRT could be considered for breast
      cancer patients suffering from menopausal symptoms resistant to alternative
      treatments, after completely informed consent is given, particularly in women
      with ER--(hormone-resistant) cancers. Unopposed estrogen therapy is known to
      increase endometrial cancer risk, and is appropriate only for hysterectomized
      women. To negate the excess risk of endometrial hyperstimulation, an adequate
      progestin dose must be given in a continuous combined regimen or for an
      appropriate number of days in sequential regimens (10 days or more for some
      progestogens or 12 days or more for other progestogens). An appropriate
      combination of estrogen and progestin does not appear to increase, and may even
      decrease, the risk of endometrial cancer. HRT is generally considered to be
      contraindicated in endometrial cancer patients. Despite the potential risks, HRT
      could be considered for patients suffering from menopausal symptoms resistant to
      alternative treatments, after completely informed consent is given. Available
      data suggest a reduced risk of colorectal adenoma and colon cancer in current
      users of HRT, but definitive studies are still needed. There is no
      contraindication to HRT prescription in colon cancer survivors. Consistent
      epidemiological data describe a decreased incidence of ovarian cancer with oral
      contraceptive use during the reproductive years. Studies on HRT and risk of
      epithelial ovarian cancer have produced conflicting results but most data seem to
      exclude a strong association. While no data contraindicate HRT use in epithelial
      ovarian cancer survivors, current studies do not allow us to exclude the
      possibility that estrogens alone could stimulate ovarian cancer growth in a small
      fraction of patients. Additional studies are required. It is important to
      consider that not all estrogens and progestins are used with the same dosage,
      route of administration (oral, transdermal and for estradiol intranasal) and,
      mostly, different estrogens do not show the same bioavailability and tissue
      effects. The available data do not allow to discriminate for all these variables
      and therefore it is inappropriate to consider jointly all forms of hormonal
      therapy. This issue is considered as an important area for future evaluation and
      research. The International Menopause Society is in the process of drawing up
      specific recommendations for further research in the field of HRT and cancer.

PMID- 11588942
TI  - The life and times of the estrogen receptors: an interim report.
AB  - The estrogens profoundly influence the growth, differentiation and function of
      the organs of the reproductive system such as the breast, uterus and ovary, but
      also have an effect on the non-reproductive tissues of the skeletal,
      cardiovascular and central nervous systems. Formerly, only one estrogen receptor
      (ER) was thought to mediate all functions. Now termed ER alpha, this agent was
      known to reside in the nucleus, to be activated by ligand and to direct the
      expression of target genes. A second oestrogen receptor (ER beta) has been
      identified, and estrogen influence has been further clarified through
      demonstration of actions which operate via membrane receptors and non-genomic
      pathways. This review summarizes our growing understanding of receptor structure,
      mechanism of action and tissue distribution, together with the implication of
      these data for the development and clinical delivery of estrogen replacement
      regimens.

PMID- 11588943
TI  - Effects of tibolone on the endometrium.
AB  - OBJECTIVE: To investigate the effects of 24 months of tibolone treatment on the
      endometrium in postmenopausal women. DESIGN: An open, prospective, multicenter
      study with a treatment duration of 24 months. POPULATION: One hundred and fifty
      healthy postmenopausal women. METHODS: Women were treated with one tablet of
      tibolone (2.5 mg Org OD14) daily. Endometrial biopsies were taken at baseline, 12
      months (n = 112) and 24 months (n = 62) to investigate endometrial histology by
      means of light microscopy. RESULTS: No stimulation of atrophic endometrium was
      observed in 98.2% and 91.9% of the analyzed women after 12 and 24 months,
      respectively. A change from an atrophic endometrial pattern to a weakly
      proliferative pattern was seen in 1.8% (95% confidence interval (CI) 0.22-6.45)
      and 6.5% (95% CI 1.20-7.51) of the women after 12 and 24 months, respectively. In
      one woman, the endometrial pattern after 24 months was classified as simple
      hyperplasia (1.6%; 95% CI 0.01-3.20). The low incidence of proliferation and/or
      hyperplasia corresponds to that seen in other clinical trials in which women have
      been treated with placebo. Vaginal bleeding and/or spotting was reported by 18
      women (12%), all showing an atrophic endometrium at all assessments, except for
      one woman with a proliferative endometrium at 24 months. CONCLUSION: In the
      majority of women (92%), the endometrium remained atrophic during 24 months of
      tibolone treatment.

PMID- 11588944
TI  - Lipid-independent effects of an estrogen-statin combination: inhibition of
      expression of adhesion molecules and plasminogen activator inhibitor--I in human
      endothelial cell cultures.
AB  - OBJECTIVE: Estrogens have been shown to elicit beneficial effects on the
      cardiovascular system by modulating the lipid profile as well as by direct
      vascular actions. Since estrogenic cardioprotection has still been not confirmed
      by randomized interventional trials, the combination with statins, which have
      been proved to act in a cardioprotective fashion, is of special interest. Statins
      are lipid-lowering drugs, but direct vascular effects also seem to be of
      importance in this case. Apart from some clinical studies investigating the
      effect of such combination therapy on the lipid profile, no reports of a possible
      influence on biochemical markers of vascular function are yet available. The aim
      of the present study was to investigate, for the first time, lipid-independent
      effects of an estrogen-statin combination on markers of vascular endothelial
      function. METHODS: Experiments were conducted using endothelial cell cultures
      from human umbilical veins. Markers of endothelial function chosen were adhesion
      molecules, which are involved in the early stages of atherosclerosis, and
      plasminogen activator inhibitor-1 (PAI-1), which is an independent risk factor
      for the development of cardiovascular disease. The concentrations of soluble
      forms of the adhesion molecules E-selectin and intercellular adhesion molecule
      (ICAM) as well as concentrations of PAI-1 were measured after the addition of 17
      beta-estradiol, fluvastatin and equimolar combinations of the two in
      concentrations of 0.01, 0.1 and 1 mumol/l. RESULTS: Both drugs significantly
      reduced concentrations of E-selectin and ICAM, and the effect of the combination
      was not superior to that of the monosubstances. In addition, both substances were
      able to inhibit the synthesis of PAI-1. In this case the effect of the
      combination was significantly greater than that of the monosubstances.
      CONCLUSION: In summary, an estrogen-statin therapy is able to elicit lipid
      independent positive modulations on the expression of cell adhesion molecules and
      the synthesis of PAI-1. The estrogen-statin combination showed partially additive
      effects and no negative, antagonistic actions. Since the combination of statins
      with hormone replacement therapy may attain clinical significance in preventing
      cardiovascular disease, it seems worthwhile to elucidate further the direct
      vascular effects of this combination therapy, especially in postmenopausal women
      with pre-existing coronary disease.

PMID- 11588945
TI  - Estimation of hormone replacement therapy influence on serum galanin level in
      postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of exogenous
      hormones (estradiol and progestogen) used in hormone replacement therapy (HRT) on
      the serum galanin level in postmenopausal women with normal body weight. METHODS:
      We studied 20 postmenopausal patients (mean age 52.3 +/- 5.2 years) before and
      after 1 year of HRT. The mean duration of amenorrhea in these patients was 5.3 +/
      4.1 years. In all cases, body mass index was in the normal range (between 20 and
      25 kg/m2). Serum galanin and estradiol concentrations were measured by
      radioimmunoassay before and after 1 year of treatment. Results were statistically
      analyzed with the use of specialist computer software. RESULTS: There was no
      statistically significant difference in serum galanin concentration before (8.24
      +/- 3.63 pg/ml) and after (5.63 +/- 2.75 pg/ml) 1 year of HRT. Following HRT the
      serum estradiol level (0.09 +/- 0.015 ng/ml) was significantly higher than before
      starting therapy (0.021 +/- 0.018 ng/ml) (p < 0.001). Also, after HRT the mean
      serum follicle stimulating hormone (FSH) level (32.9 +/- 28.0 IU/l) was
      significantly lower than before starting therapy (91.7 +/- 38.5 IU/l) (p < 0.01).
      CONCLUSIONS: The study results suggest that HRT in postmenopausal women does not
      restore galanin levels to values typical of those in women of reproductive age.

PMID- 11588946
TI  - Influence of female and male sex steroids on body composition in the rabbit
      model.
AB  - OBJECTIVE: To study the influence on body composition of estrogen replacement
      therapy (ERT) in female rabbits and of replacement therapy with testosterone
      (TRT) in male rabbits using dual-energy X-ray absorptiometry (DEXA). METHODS:
      Cholesterol-fed female and male rabbits receiving a weight-restricted diet (100
      g/day) were used. Total lean tissue mass (LTM), total body fat tissue mass (FTM)
      and total tissue mass (TTM) were determined by DEXA at baseline, after which the
      animals were gonadectomized and treated with sex steroids. Soft body composition
      was then determined again after 30-31 weeks of treatment. RESULTS: Relative to
      controls, ERT with estradiol (E2) doses of 2 and 4 mg/day significantly increased
      LTM (p < 0.001), whereas E2 0.5 and 1 mg/day had a neutral effect on LTM. The
      change in fat mass, however, was not statistically significant between groups. In
      male rabbits, compared with castrated control rabbits, LTM decreased in
      testosterone-treated animals (by 7-12%; p < 0.001) but FTM decreased relatively
      more (by 66-79%; p < 0.0001). In both genders, body weight correlated with TTM as
      determined by DEXA (r = 0.89-0.91, p < 0.0001). CONCLUSION: In this in vivo model
      of growing rabbits, estrogen replacement significantly increased LTM in female
      animals, whereas testosterone replacement significantly decreased FTM in males,
      suggesting that soft body composition of both genders is significantly affected
      by replacement with sex steroids. Until comparable human data are available, it
      is speculated that similar changes in soft body composition may occur in humans
      treated with sex steroids.

PMID- 11588947
TI  - Comparison of effects of continuous combined transdermal with oral estrogen and
      oral progestogen replacement therapies on serum lipoproteins and compliance.
AB  - OBJECTIVE: To compare the effects of transdermal and oral hormone replacement
      therapy on compliance and serum lipoproteins. DESIGN: A total of 159 naturally
      menopausal women who received either 0.05 mg transdermal estradiol twice weekly
      or 0.625 mg oral conjugated estrogen daily, with 2.5 mg oral medroxyprogesterone
      acetate daily, were retrospectively studied. Continuation with or drop-out from
      treatment regimens, side-effects and bleeding patterns were recorded during a 2
      year follow-up period. Baseline, first-year and second-year serum lipoprotein
      levels were compared between the two groups. RESULTS: Of the 100 women taking
      oral estrogen, 28 (28%) had dropped out whereas of the 59 women receiving
      transdermal estrogen, 17 (28.8%) had dropped out at the end of 2 years. The
      occurrence of bleeding episodes was the most common reason given for
      discontinuation in both treatment groups (52.9% in the transdermal group and
      35.7% in the oral treatment group). The mean increase in high-density lipoprotein
      (HDL) level for the first year and second year was 10.2 +/- 3.2% and 31.4 +/-
      2.8%, and 13.5 +/- 3.2% and 33.6 +/- 3.6% with oral treatment and transdermal
      therapy, respectively. The mean decrease in total cholesterol for the first year
      and second year was 2.9 +/- 1.9% and 14.7 +/- 1.6%, and 5.6 +/- 1.7% and 5.7 +/-
      1.6% with oral and transdermal treatment, respectively. Likewise, the mean
      decrease in low-density lipoprotein (LDL) cholesterol for the first year and
      second year was 6.2 +/- 2.5% and 18 +/- 2.9%, and 7.9 +/- 3.0% and 15.9 +/- 5.2%
      with oral and transdermal treatment, respectively. There was no significant
      difference between groups in any of the lipid parameters. Transdermal treatment
      decreased triglyceride levels by 33.7 +/- 3.9%, whereas oral estrogen treatment
      increased triglycerides by 18.6 +/- 4.3% at the end of 2 years. This difference
      between the two groups was statistically significant (p < 0.0001). CONCLUSION:
      Continuation of treatment was similarly high at the end of 2 years with both
      transdermal and oral estrogen treatment. Both treatments changed serum lipids
      favorably. Nevertheless, triglycerides were increased by oral estrogen but
      decreased by transdermal treatment at 2 years; this difference between the groups
      was significant.

PMID- 11588948
TI  - Longitudinal study of hormone levels and depression among women transitioning
      through menopause.
AB  - OBJECTIVE: To address the association between depression and absolute levels of
      estradiol, and change in estradiol, among women during the menopausal transition.
      METHODS: This was a prospective, observational study conducted in Massachusetts,
      USA. Analyses reported here are based on the first three interviews following
      baseline (T1-T3). The participants were 309 women aged initially 43-53 years, who
      contributed a total of 728 observations (mean number of observations per subject
      2.36). The main outcome measure was depression as measured by the Center for
      Epidemiologic Studies-Depression (CES-D) scale. RESULTS: CES-D score was not
      significantly associated with menopause status categories, nor was it associated
      with annual change in estradiol level (E2) (p = 0.19). The unadjusted association
      between log E2 and CES-D was negative (odds ratio 0.69) and statistically
      significant (p = 0.03). Upon adjustment for symptoms, however, the association
      remained negative but was no longer statistically significant (p = 0.26). Hot
      flushes/night sweats were positively associated with CES-D (p = 0.04), and
      trouble sleeping was strongly positively related to CES-D (p < 0.001).
      CONCLUSIONS: Results provide strong support for the domino or symptom hypothesis,
      which posits that depressed mood is caused by vasomotor symptoms associated with
      changing estrogen levels. Estradiol did not have a direct effect, independent of
      symptoms. This study adds to the body of literature suggesting that any
      association found between menopause and depression is most likely to be explained
      by other factors, such as symptoms and sleep problems. Findings also highlight
      the importance of studying the complex relationship between hormone levels, sleep
      problems and vasomotor symptoms during the menopausal transition.

PMID- 11588949
TI  - Prevalence of and satisfaction with complementary therapies and hormone
      replacement therapy in a specialist menopause clinic.
AB  - OBJECTIVE: To assess the usage of both conventional and complementary therapies
      by peri- and postmenopausal women for the treatment of menopausal symptoms.
      METHOD: A prospective questionnaire was completed by 200 consecutive patients
      attending a tertiary referral London-based specialist menopause clinic between
      September and December 1999. RESULTS: The median age of responders was 53.5 years
      (interquartile range 49-59). In total 137 women (68.5%) had ever tried an
      alternative treatment for the relief of their menopausal symptoms. Of these women
      66% were regular users and 62% were satisfied with the effects of treatment.
      Women younger than the median age were significantly more likely to have used
      complementary therapies than older women (p = 0.036). Of the 200 participants,
      184 women (92%) were current users of conventional hormone replacement therapy
      (HRT), and 89% were satisfied with the effects that their current HRT regimen had
      on their menopausal symptoms. Age was not related to satisfaction with
      conventional or complementary medicines. General practitioners and hospital
      doctors accounted only for 17% and 9%, respectively, of the primary sources of
      information for complementary medicines. CONCLUSIONS: High rates of usage and
      satisfaction were found with both conventional and complementary treatments for
      the relief of menopausal symptoms in our unit. For many of the women, both types
      of medicine are taken concurrently. Both general practitioners and hospital
      doctors are poor primary sources of information on complementary therapies for
      menopausal women.

PMID- 11588950
TI  - [Clinical and morphological features of pulmonary tuberculosis in relation to the
      patients' social status and the degree of ecologically pathogenic load of areas
      in the Saratov Region].

PMID- 11588951
TI  - [Activity of the renin-angiotensin-aldosterone system and its impact on the
      effectiveness of treatment of chronic heart failure in patients with pulmonary
      tuberculosis].
AB  - The renin-angiotension-aldosterone system (RAAS) was studied in 93 patients with
      pulmonary tuberculosis complicated by chronic heart failure (CHF).
      Radioimmunoassay was used to determine plasma renin activity (PRA) and serum
      angiotensin I and aldesterone levels. There was higher RAAS activity, as shown by
      elevated PRA. RAAS activity decreased during CHF treatment with angiotension
      converting enzyme inhibitors (captopril, ramipril, prestarium) and an angiotensin
      II-receptor blocker (cosaar), which is indicative of the efficiency of CHF
      treatment.

PMID- 11588952
TI  - [Effectiveness of chemotherapy of intrathoracic tuberculosis in children: late
      follow-up data].
AB  - Clinical and X-ray studies were made in 148 children 2-10 years after hospital
      treatment to evaluate the stability of clinical recovery by the frequency of
      relapses in relation to the use of different drug treatment regimens. Children
      from an experimental group (n = 75) received shorter chemotherapy with 3-4 drugs
      (isoniazid, rifampicin, pyrazinamide in uncomplicated tuberculosis plus
      streptomycin in complicated one) in the intensive phase of chemotherapy.
      Pyrazinamide was not used in the intensive phase in the control group (n = 73).
      Long-term follow-ups showed a high efficiency of shorter chemotherapy regimens in
      treating intrathoracic tuberculosis in children since they do not lead to the
      higher incidence of recurrences--2.7% in both groups. The latter occurred in
      adolescents who had severe residual changes, who had been irregularly followed up
      at the tuberculosis control dispensary after hospital discharge, who had not
      received seasonal preventive chemotherapy courses, and who had experienced
      complicated, generalized or acute tuberculosis.

PMID- 11588953
TI  - [State of local immunity in patients with inflammatory diseases of the spine].
AB  - The paper presents the results of examination of spinal fluid in tuberculous
      spondylitis (n = 83), its sequelae (n = 58), spinal osteomyelitis (n = 25) for
      the levels of tuberculosis antibodies (TAb) by applying the routine enzyme
      immunoassay, specially adapted to this biological object, and immunoglobulins. A
      relationship was found between TAb detection and the rate of the process and the
      severity of a spinal cord lesion. Forty one patients had severe spinal cord
      disorders (paraplegia and deep paraparesis). To detect TAb in CF is shown to be
      of differential diagnostic value. There is new evidence for impaired blood-brain
      and immunological barriers in active tuberculosis in the spine with spinal cord
      compression.

PMID- 11588954
TI  - [Informative value of bronchoalveolar lavage and expired air vapor condensate in
      the diagnosis of acute pneumonia].

PMID- 11588955
TI  - [Effectiveness of dirotone in the treatment of chronic cor pulmonale].

PMID- 11588956
TI  - [Factors of local nonspecific lung protection in the time course of acute and
      lingering pneumonia].
AB  - The indices of local nonspecific lung protection in the bronchoalveolar lavage
      fluid and cells were studied in 20 patients with acute pneumonia and 20 patients
      with lingering pneumonia. In acute pneumonia, the cellular and humoral links of
      local protection were found to have an adequate responsiveness and to preserve
      their protective properties during conventional therapy. In lingering pneumonia,
      the phagocytic and microbicidal properties of alveolar macrophages and the levels
      of lysozyme and sIgA in the bronchoalveolar lavage were lower. In the patients
      with lingering pneumonias who underwent a course of conventional therapy, these
      indices fail to recover to a greater extent, neutrophilic lung remained high.
      Correspondingly, the values of neutrophilic infiltration, macrophageal phagocytic
      and microbicidal activities and the levels of lysozyme and sIg-A may be serve as
      markers of the lingering course of acute pneumonias.

PMID- 11588957
TI  - [Epidemic situation of tuberculosis among HIV-infected patients in Russia and a
      system of preventive measures].
AB  - The paper shows a poor prognosis of tuberculosis spread among HIV-infected
      patients in Russia for the years immediately ahead. Recommendations are given how
      to organize a tuberculosis controlling care to patients with HIV infection by
      taking into account its stages by aspects, such as prevention, diagnosis, medical
      examination, and treatment.

PMID- 11588958
TI  - [Special features of the course of tuberculosis in HIV-infected patients].

PMID- 11588959
TI  - [HIV infection and tuberculosis in the Republic of Kazakhstan].
AB  - The incidence of HIV infection is now recorded in all 14 regions of the Republic
      of Kazakhstan and in the cities of Astana and Almaty. A total of 1010 HIV
      infected persons were recorded as of January 1, 2000. There were 29 patients with
      AIDS. Tuberculosis was detected in 93 of the HIV-infected patients recorded as of
      January 1, 2000, which amounts to 12.5% of the examinees. It was found in 39 of
      the HIV-infected prisoners, which accounts for 41.9% of the total number of
      patients having a contaminant infection and for 19.4% of those convicted.
      However, it should be believed that these data do not reflect the true state of
      affairs, which involves some difficulties associated with the diagnosis of
      tuberculosis in patients HIV infection both in its early and late stages.

PMID- 11588960
TI  - [Effectiveness of culture and bacterioscopic methods in new cases of pulmonary
      tuberculosis].

PMID- 11588961
TI  - [Detection of antigen-binding lymphocytes in the diagnosis of tuberculosis].
AB  - The efficiency of diagnosis of active tuberculosis was evaluated from detection
      of tuberculin-receptor lymphocytes [antigen-binding lymphocytes (ABL)] by the
      indirect rossette-formation test with the red blood cell reagent designed. Sixty
      two patients with tuberculosis (of them 10 patients with extrapulmonary
      tuberculosis), 10 with lobular pneumonia, and 27 healthy individuals cal were
      examined. Positive results of fluography, smear microscopy, bacteriological
      study, leukocytic migration inhibition test, and test for ABL were obtained in
      84, 40, 50, 39, and 100%, respectively. The controls had negative tests. Thus,
      ABL detection was the method of choice in tuberculosis diagnosis.

PMID- 11588962
TI  - [Testing Mycobacterium tuberculosis for drug sensitivity using different
      methods].
AB  - Testing 35 Mycobacteria tuberculosis strains isolated from patients for drug
      sensitivity on the Lowenstein-Yersen, Middlebrook 7 H11 midia and by using the
      polymerase chain reaction demonstrated a correlations of the results obtained by
      these methods. In laboratory practice, the use of all possible of guidelines for
      testing Mycobacteria tuberculosis for drug sensitivity.

PMID- 11588963
TI  - [Specific features of Mycobacteria isolated from patients and animals with
      tuberculosis and from environmental objects].
AB  - Two hundred samples from environmental objects, such as soil, manure, water,
      feeds, et.), 129 isolates from tuberculosis patients' sputum, and 222 samples
      from tuberculin-responsive animals were studied. Mycobacteria of atypical forms
      were found to be widely distributed in the environment. The causative agents of
      bovine-type tuberculosis could be isolated from both tuberculin-responsive
      animals and environmental objects of tuberculosis-burdened firms. The cultural
      morphological and biochemical properties were studied in 129 isolates from
      tuberculosis patients' sputum. Of them, 91 (75.8%) and 29 (24.2%) samples were
      defined as M. tuberculosis and M. bovis, respectively. Nine samples could not be
      identified for different reasons.

PMID- 11588964
TI  - [Specific features of thanatogenesis of respiratory tuberculosis in
      penitentiaries].
AB  - The causes of death were analyzed in 112 patients treated at the interregional
      tuberculosis hospital. Some peculiarities in the thanatogenesis of pulmonary
      tuberculosis were revealed in penitentiaries: the deceased had more commonly
      infiltrative and disseminated tuberculosis than fibrocavernous, there was a high
      incidence of complications in 75% of dead persons who had exhaustion and cachexia
      that resulted in reduced defensive forces. The high (17%) pulmonary bleeding as a
      cause of death in three fourths of the those who died resulted from acute
      progressive tuberculosis.

PMID- 11588965
TI  - [Antituberculosis antibodies in patients with tuberculosis during chemotherapy].
AB  - Enzyme immunoassay of the titer of antituberculosis antibodies (ATAb) from
      patients with pulmonary tuberculosis has indicated that their levels depend on
      the different characteristics of a specific process: the form of active
      tuberculosis, the extent of changes in the lung tissue, the presence of
      destruction and bacterial isolation, the type of specific inflammatory reaction,
      and the duration of the treatment performed. Whether there was a correlation of
      ATAb titers with skin tuberculin sensitivity the level was studied by the Mantoux
      test using 2 TE PPD-L. The time course of changes in ATAb titers in patients with
      pulmonary tuberculosis during the routine chemotherapy was analyzed.

PMID- 11588966
TI  - [Molecular medicine and treatment of tuberculosis].

PMID- 11588967
TI  - [The phospholipid spectrum of platelet membranes in patients with COPD in the
      abating exacerbation phase].
AB  - Clinical and laboratory studies have been performed in 120 patients with chronic
      obstructive diseases of the lung (CODL) and in 35 healthy individuals in order to
      determine the content of different phospholipid fractions in the platelet
      membranes and their proportions at the beginning of their medical rehabilitation
      after pulmonological hospital treatment (recurrent exacerbation). It has been
      found that membranosystemic disorders in CODL represent a major pathogenetic link
      in the vicious circle of disease progression and the routine therapy is low
      effective and has no membrane-repairing effect. This makes it necessary to
      develop and search for new pathogenetic treatments of CODL, which are to exert a
      membranotropic effects on the whole body.

PMID- 11588968
TI  - [Successful treatment of subclavian thrombophlebitis in a patient with pulmonary
      tuberculosis].

PMID- 11588969
TI  - [Acid-resistant microorganisms: Mycobacteria, Nocardia, Rhodococci, chemical
      composition, biological properties, antigenic structure].

PMID- 11588970
TI  - [Contents and methods of training of foreign students].
AB  - By analyzing their own experience in training foreign students, the authors
      concluded that University education in phthisiology may be improved by increasing
      a role of independent work by using the special text-book prepared by the
      Department of Tuberculosis, Kursk State Medical University.

PMID- 11588971
TI  - [History of phthisiology teaching at the Kazan Medical University].

PMID- 11588972
TI  - [Analytical review of dissertation studies in the area 14.00.26 "Phthisiology"
      approved by the Higher Certifying Commission, Ministry of Education of the
      Russian Federation in 2000].

PMID- 11588973
TI  - [Tuberculosis in Russia in the late 20th century].
AB  - The present tuberculosis epidemic situation in Russia is marked by an increasing
      role of exogenous infection. The peak deteriorated epidemic situation was
      observed in 1993 and 1999. There was a considerable deterioration of the epidemic
      situation in 1999 due to the economic crisis in August 1998, which caused a
      drastic fall in living conditions. Trends for an epidemic process changed in the
      1990s. Spread of tuberculous infection occurs by the same mechanisms as did in
      the early 20th century. The official incidence of tuberculosis does not
      completely reflect actual morbidity (nearly by 15%) due to the fact that patients
      with tuberculosis have not been detected.

PMID- 11588974
TI  - Amalgam in waste water.

PMID- 11588975
TI  - The importance of prosthodontics in radiation therapy.

PMID- 11588976
TI  - Detection and management of the dental patient with hypertension.

PMID- 11588977
TI  - Proceedings of the 8th International Congress on Neuronal Ceroid Lipofuscinoses
      (Batten Disease). Oxford, United Kingdom, September 2000.

PMID- 11588978
TI  - High resolution MRI reveals global changes in brains of Cln3 mutant mice.
AB  - Batten disease, the juvenile-onset form of neuronal ceroid lipofuscinosis (NCL),
      is a progressive neurodegenerative disorder of childhood with an age of onset of
      5-10 years of age. JNCL is caused by mutations in the CLN3 gene which encodes a
      membrane protein of unknown function. Magnetic resonance imaging of the brain of
      juvenile NCL patients has revealed changes in signal intensity and tissue
      atrophy, predominantly in the cortex and cerebellum. A mouse model for Batten
      disease was created by targeted disruption of the murine Cln3 gene in order to
      further understanding of the pathophysiology of Batten disease and to evaluate
      potential therapeutic approaches. Several features of the disease are displayed
      by Cln3 mice including accumulation of characteristic storage material in
      neurons. The aim of this work was to investigate neurodegeneration in the Cln3
      mouse model using high resolution magnetic resonance imaging to measure signal
      intensity ratios in selected regions of interest. Global changes were observed in
      the brains of 12-month-old mutant mice that mirror those seen in juvenile NCL
      patients. There is a decrease in signal intensity ratio in grey matter regions
      including cortex, hippocampus and cerebellum, tissues where neuronal storage
      accumulation and cell loss have been seen in the mouse model. The alterations
      seen in Cln3 mutant mice support the validity of further imaging studies and
      suggest that this method will have application in assessment of therapeutic
      approaches in the study of mutant mouse models of NCL including the Cln3 mouse.

PMID- 11588979
TI  - Mouse gene knockout models for the CLN2 and CLN3 forms of ceroid lipofuscinosis.
AB  - The childhood neuronal ceroid-lipofuscinoses (NCLs) are autosomal-recessively
      inherited neurodegenerative disorders that result in severe cognitive decline and
      premature death. The genetic bases for a number of different forms of NCL,
      including those designated CLN2 and CLN3, have now been determined. However, the
      mechanisms by which the gene defects cause the disease pathology are not known
      and no effective treatments for these disorders have been developed. To provide
      tools for studying the mechanisms underlying the disease pathologies and for
      screening potential therapeutic interventions, work is under way to develop mouse
      models for the CLN2 and CLN3 disorders. Targeted gene replacement was used to
      generate mice in which the murine orthologue of the CLN3 gene has been knocked
      out. Mice that are homozygous for the Cln3 knockout allele develop a number of
      pathological features similar to those that occur in the human disorder. Among
      these are accumulation of autofluorescent lysosomal storage bodies, behavioural
      abnormalities, retinal degeneration, and premature death. On a mixed strain
      genetic background, the appearance of these symptoms was quite variable,
      suggesting that other genes can modify the effects of CLN3 mutations. Work to
      develop a similar mouse gene knockout model for the CLN2 disorder is well under
      way. Chimaeric mice have been developed with cells that carry an induced mutation
      in the mouse orthologue of the CLN2 gene that would prevent synthesis of a
      functional CLN2 protein in mice that are homozygous for the mutation. Mice will
      be developed that are homozygous for this mutation, and these animals will be
      evaluated for the development of pathologies similar to those that occur in the
      human disorder.

PMID- 11588980
TI  - Lysosomal membrane proteins.
AB  - The lysosomal system is the main intracellular mechanism for the turnover of
      endogenous and exogenous macromolecules. This catabolism is brought about in the
      lumen of lysosomes by a cocktail of predominantly hydrolytic enzymes with
      characteristic acidic pH-optima. The lysosomal membrane, which has a typical
      single phospholipid bilayer, controls the passage of material into and out of
      lysosomes, by its permeability and ability to fuse with digestive vacuoles or
      engulf cytosolic material. About 20 systems for transporting small molecules
      across the lysosomal membrane have been characterized but only two proteins,
      cystinosin and sialin, involved in the transport of cystine and sialic acid,
      respectively, have been cloned. A distinct, vacuolar proton pump (V-type H+
      ATPase), which maintains the low luminal pH, has been characterized. Ubiquitous,
      highly glycosylated, integral membrane proteins of largely unknown function,
      called lysosome-associated membrane proteins (LAMPS) or lysosomal integral
      membrane proteins (LIMPS), account for about 50% of the protein in the lysosomal
      membrane. They have a short cytosolic domain of 10-20 amino acids containing
      single tyrosine or di-leucine motifs, which interact with adaptor complexes (APS)
      for sorting at the trans-Golgi network and targeting to lysosomes. A deficiency
      of LAMP-2 is the primary defect in Danon disease. Other proteins associate with
      the membrane transiently or cell-specifically. The structure, function and
      intracellular transport of these different classes of lysosomal membrane proteins
      will be reviewed.

PMID- 11588981
TI  - Caenorhabditis elegans homologues of the CLN3 gene, mutated in juvenile neuronal
      ceroid lipofuscinosis.
AB  - Neuronal ceroid lipofuscinoses (NCLs) are the most common hereditary
      neurodegenerative disorders of childhood. The first symptom of this heterogeneous
      group of devastating lysosomal storage diseases is progressive visual failure.
      The different forms of NCL can be distinguished by age of onset, clinical
      features and the characteristics of the accumulated materials. The juvenile form,
      Batten-Spielmeyer-Vogt disease which is caused by mutations in the CLN3 gene, is
      the most frequent form of the disease in which loss of vision becomes apparent
      around the age of 5-8 years. The gene was found to encode a novel integral
      membrane protein localizing to the lysosomes, confirming that the primary defect
      in NCL is in lysosomal function. The CLN3 protein function is still unknown, and
      is examined in several model organisms. We are studying the nematode
      Caenorhabditis elegans, and have identified three CLN3 homologues. In order to
      investigate the role of the CLN3 protein in C. elegans, Cecln-3 deletion mutants
      are being isolated from an ethyl methanesulphonate (EMS)-induced deletion mutant
      library. Examination of these mutants may provide us with information that will
      help in dissecting the processes in which the CLN3 protein is involved. In this
      library two mutated C. elegans Cln-3 loci have been identified, of which one
      mutant, NL748, was isolated. This mutant contains a deletion of the whole gene.
      The deletion mutant was characterized with regard to life expectancy, and showed
      no significant differences when compared with wild-type.

PMID- 11588982
TI  - Genomic structure of three CLN3-like genes in Caenorhabditis elegans.
AB  - The genome of Caenorhabditis elegans is predicted to carry three genes similar to
      CLN3, the gene underlying juvenile neuronal ceroid lipofuscinosis. All three
      genes are transcribed and the genomic structure has been determined. The number
      and position of exons for two of the genes differ from that predicted from the
      genomic sequence, but no discrepancies with the genomic nucleotide sequence were
      found. Gene F07B10.1 (cln-3.1) is predicted to have 7 exons and to encode a
      protein of 424 amino acids. Gene C01G8.2 (cln-3.2) has 9 exons and encodes a
      protein of 435 amino acids. Gene ZC190.1 (cln-3.3) is predicted to have 9 exons
      and to encode a protein of 416 amino acids.

PMID- 11588983
TI  - A yeast model for classical juvenile Batten disease (CLN3).
AB  - The gene involved in the classical juvenile form of Batten disease, CLN3 has been
      identified as being highly homologous to the Saccharomyces cerevisiae YHC3 gene.
      To provide a simple model for the biochemical events underlying this disease,
      several disruptions have been made in YHC3 in three different S. cerevisiae
      strains. No obvious growth differences were observed, and neither was the
      previously reported phenotypic difference between wild-type and yeast disrupted
      in YHC3.

PMID- 11588984
TI  - ATP synthase activity in ovine ceroid lipofuscinosis [OCL6].
AB  - We measured ATP synthase activities in mitochondria isolated from livers of lambs
      with ceroid lipofuscinosis (OCL6) and compared them with those from similar
      isolations from obligate heterozygous and control lambs. Addition of excess Ca2+
      to the incubation mixture resulted in an up-regulation of activity in
      mitochondria from control lambs but down-regulation in those from OCL6 affected
      lambs. The mean change in activity with Ca2+ for heterozygous animals was midway
      between those from control and affected groups being significantly different from
      control but not from affected. The change in ATP synthase activity to added Ca2+
      was also measured in isolated mitochondria from affected and control lambs from 3
      days to 25 months of age. As above, there was down-regulation to the addition of
      Ca2+ in affected lambs. There was a fall in percentage change to Ca2+ with age in
      both affected and control lambs. This was not significantly different in affected
      lambs indicating it was not associated with the stage of disease. The above in
      vitro results, if extrapolated to neurons in vivo, imply a potential dysfunction
      of mitochondria in OCL6 lambs that could lead to calcium mediated neurotoxicity
      and neuron death due to production of free radicals as implicit in the energy
      linked excitotoxic hypothesis.

PMID- 11588985
TI  - Changes in GABAergic neuron distribution in situ and in neuron cultures in ovine
      (OCL6) Batten disease.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited human and
      animal diseases characterized by progressive brain atrophy. A form in sheep is
      syntenic to the human CLN6 disease. Cell type specific neurodegeneration in these
      sheep was indicated by the distribution of GABAergic interneurons in coronal
      sections of normal and CLN6 affected sheep brains. A reduction of parvalbumin
      immunoreactive neurons in NCL cerebral cortex was the most striking feature. This
      was most pronounced in parietal cortex where very few positive cells remained.
      Calretinin immunoreactive somata in infragranular layers of the neocortex were
      also reduced while the number of calbindin positive cells was similar in affected
      and normal brains. There were fewer GAD immunoreactive neurons in the deeper
      layers of all NCL cortical areas examined. The parietal lobe was relatively more
      affected than frontal or temporal lobes while the cerebellum and the basal
      ganglia showed no signs of selective neuron loss. Since horizontally extending
      basket cells are mainly labelled by parvalbumin, the loss of these interneurons
      in the neocortex may render pyramidal neurons more excitable and compromise their
      co-ordinated output. In vitro, cultures of control and affected neurons from 60
      to 70-day-old fetal brain hemispheres were examined for the presence of GABAergic
      and glutamatergic neurons. Different neurons developed distinct immunoreactivity
      to glutamate or GABA but the overall distribution was similar in normal and
      affected cultures. This culture system may provide a useful model to compare
      GABAergic cell function of normal and NCL affected neurons.

PMID- 11588986
TI  - Altered levels of high-energy phosphate compounds in fibroblasts from different
      forms of neuronal ceroid lipofuscinoses: further evidence for mitochondrial
      involvement.
AB  - The pathogenesis of neurodegeneration in neuronal ceroid lipofuscinosis (NCL) is
      still not clear despite progress in mutation analysis of these diseases. We have
      recently observed anomalies at the level of the mitochondrial ATPsynthase
      (complex V of the respiratory chain) in fibroblasts from children with CLN1,
      CLN2, CLN3 and in an ovine model (OCL6). The measurements were carried out in
      vitro. If these alterations were of relevance in vivo as well, contents of high
      energy phosphate compounds should be reduced. In the present study, we measured
      levels of creatine phosphate (CP), ATP, ADP and AMP in fibroblasts from children
      with CLN1, CLN2, CLN3 and in OCL6. ATP was reduced to about 50% of normal in
      CLN1, CLN2 and CLN3, ADP was about 30% of normal in these cells, and CP was 50%
      of normal in CLN1 and CLN2 but remained normal in CLN3. In fibroblasts of NCL
      sheep, however, CP and ADP were increased to 690% and 220% of normal,
      respectively, while ATP remained normal. If the anomalies found in cellular
      energy metabolism in fibroblasts were expressed in neurons from NCL patients and
      NCL sheep 'slow-onset excitotoxicity' could occur leading to cellular dysfunction
      and eventually to cell death.

PMID- 11588987
TI  - Batten disease and the control of the Fo subunit c pore by cGMP and calcium.
AB  - Subunit c of ATP synthase functions as a high conductance ion channel, tightly
      regulated by calcium. We have suggested that the pathogenesis of Batten syndromes
      involving overaccumulation of subunit c are linked to the protein's ion channel
      function. In normal electrically excitable tissue the channel could act as a
      pacer setting nodal voltage via control of cation entry. The channel conductance
      is controlled by voltage, calcium, cyclic nucleotides and polyamines. We discuss
      the pathogenic role that subunit c could play in the electrically excitable
      tissues of retina, brain and heart where Batten neurodegeneration is seen. Focus
      is given to potential links between subunit c and the known mutant gene products
      in the Batten diseases, the process of apoptosis, and the requirement of the
      growing brain for gradients of cGMP, a ligand of the subunit c channel.

PMID- 11588989
TI  - Clinical and neuroradiological diagnostic aspects of neuronal ceroid
      lipofuscinoses disorders.
AB  - Early diagnosis is mandatory for avoiding further cases in families with
      hereditary metabolic brain disorders. This review lists the most important
      clinical symptoms and neuroradiological findings at the early stage of the seven
      most common childhood neuronal ceroid lipofuscinoses (NCL) types. In the
      infantile type the typical magnetic resonance imaging (MRI) findings can be seen
      even before the clinical signs. In the classic late infantile type (CLN2), MRI is
      less informative but in this and in the variant late infantile type CLN6 the
      characteristic neurophysiological findings are present at an early stage,
      although not in the Finnish variant CLN5. In the latter, the clinical diagnosis
      depends on ophthalmological and MRI findings. The combination of ophthalmological
      deficits and vacuolated lymphocytes is highly characteristic of the juvenile type
      (CLN3). A new NCL type, Northern epilepsy (CLN8), is also briefly reviewed.

PMID- 11588988
TI  - Assessment of dietary therapies in a canine model of Batten disease.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative
      diseases that occur in a number of animal species, including dogs. A study was
      conducted to determine whether the resupply of nutrients lost in NCL English
      Setter dogs would modify the course of the disease. Carnitine and polyunsaturated
      fatty acids have been reported to be reduced in NCL English Setters. Therefore,
      the normal laboratory diets of NCL dogs were supplemented with carnitine, fish
      oil and corn oil and the disease progression was compared with that of an
      untreated litter mate. The following specific prognostic indicators of NCL were
      monitored: cognitive function, brain atrophy, brain glucose metabolism and
      lifespan. Carnitine, with or without lipid supplements, dramatically delayed the
      progression of cognitive decline in NCL dogs. When fish oil and corn oil only
      were supplied, brain atrophy was reduced. A combination of all three supplements
      preserved cognitive function and increased lifespan by 10%. However, brain
      glucose hypometabolism and cerebral atrophy were not reduced. The results in this
      study indicated that the effectiveness of therapeutic interventions can be
      assessed by non-invasive methods at a relatively early stage of the disease
      process. Our study suggests that dietary supplementation with carnitine is a
      promising new approach for delaying or preventing the cognitive decline in dogs,
      and perhaps, with human NCL patients.

PMID- 11588990
TI  - New antidepressive and antipsychotic drugs in juvenile neuronal ceroid
      lipofuscinoses--a pilot study.
AB  - Patients with juvenile neuronal ceroid lipofuscinosis (JNCL) often have severe
      psychiatric symptoms. These are common in their mid-teens and include such
      symptoms as anxiety and affective and psychotic disorders. The older
      antidepressants and antipsychotics do not seem to be effective and often cause
      many adverse effects. Therefore, we wanted to try the new psychotropic drugs in
      Finnish patients with JNCL. We also wanted to determine the profile of these
      drugs in this patient group. Fourteen Finnish patients with JNCL receiving
      psychotropic drug treatment with citalopram, risperidone, olanzapine or
      quetiapine, were included. The mean age at initiation of the new psychotropic
      drugs was 13.8 years. Indications for treatment were psychotic symptoms,
      affective symptoms, anxiety and an inadequate response to other psychotropic
      drugs, or even adverse reactions. Information on psychiatric symptoms and current
      treatment was gathered from interviews and from the medical records. Indications
      and the clinical outcome of the treatment were determined by a consensus of the
      assessments by parents and physicians. The psychotropic drugs most commonly used
      in Finnish patients with JNCL are citalopram and risperidone. The clinical
      outcome was good or satisfactory in 70%. The adverse effects most commonly
      reported were fatigue, weight gain and aggravation of extrapyramidal symptoms.
      Little research has been done in this area and there are no good guidelines for
      treatment of psychiatric symptoms in patients with JNCL. Therefore, every patient
      should be treated with the safest and most commonly used drugs in the lowest
      possible doses.

PMID- 11588991
TI  - Northern epilepsy syndrome (NES, CLN8)--MRI and electrophysiological studies.
AB  - Northern epilepsy syndrome (NES, EPMR, progressive epilepsy with mental
      retardation, CLN8), an inherited childhood-onset epilepsy with mental
      retardation, has been recently characterized to belong to the family of neuronal
      ceroid lipofuscinoses (NCLs). In this study, four patients (ages 26-44 years)
      with NES and eight healthy controls underwent magnetic resonance imaging (MRI)
      and electrophysiological evaluation with somatosensory evoked magnetic field
      (SEF) studies. The findings in NES were compared with the known findings in
      juvenile NCL (JNCL, CLN3) and Finnish variant late infantile NCL (vLINCLFIN,
      CLN5) that manifest around the same age as NES. Also postmortem MRI was performed
      on one brain. On the MRIs, slight to moderate cerebellar atrophy was seen in all
      patients, whereas only two patients had slightly enlarged cerebral sulci. None of
      the MRIs demonstrated signal intensity abnormalities that are commonly seen in
      JNCL and vLINCLFIN and are considered to reflect the Wallerian degeneration after
      neuronal death. Generally SEFs in NES were within normal limits, indicating that
      the disease had not impaired the function of the neurons on the somatosensory
      pathway. In conclusion, MRI imaging and SEF findings suggest that the cerebral
      neuronal death and dysfunction in NES are minimal compared with JNCL and
      vLINCLFIN.

PMID- 11588992
TI  - Transdermal fentanyl therapy for pains in children with infantile neuronal ceroid
      lipofuscinosis.
AB  - We used infantile neuronal ceroid lipofuscinosis (INCL), in which deterioration
      of the central nervous system is extremely rapid, to study constant release of an
      opioid for pains of central origin in a metabolic disease. The effect of a
      transdermal fentanyl patch was studied in five children with INCL. In two of
      them, measurements of 17 fentanyl serum concentrations and also visual analogue
      pain scale were obtained during a 15-day study period. Low doses of transdermal
      fentanyl usually provided good pain relief for the first two days, but not for
      the third day, of the three-day patch change interval. Pain relief of this type
      seems mandatory for pains mostly of central origin.

PMID- 11588993
TI  - Electroencephalography in juvenile neuronal ceroid lipofuscinosis: visual and
      quantitative analysis.
AB  - Fourteen patients with a confirmed diagnosis of juvenile neuronal ceroid
      lipofuscinosis (JNCL) (aged 6-12.5 years at the beginning of the study) were
      prospectively followed for 5 years. An electroencephalogram (EEG) was recorded
      and analysed both visually and quantitatively and a neuropsychological
      examination was performed once a year. In addition, a cross-sectional EEG study
      of 32 patients aged 5-27 years was performed. The EEG was often normal before the
      age of 9 years, and thereafter a progressive background abnormality and increase
      in paroxysmal activity took place. The EEGs were significantly slower than those
      of the controls, and the speed of slowing of EEG correlated to the decrease in
      intelligence quotients (IQ). Quantitative analysis was superior to visual
      analysis in detecting the deterioration of the background activity. The best
      parameter describing this was the fast/slow ratio. Peak frequency, percentage of
      theta and the fast/slow ratio correlated with IQ.

PMID- 11588994
TI  - Impaired temporo-occipital blood flow in an atypical CLN1 case with late
      infantile onset and granular osmiophilic deposits.
AB  - A 5-year-old boy presented with frequent absences. Speech began to regress. He
      became ataxic, barely able to walk. Studies with Xe-133 and hexamethylpropylene
      amine oxime single-photon emission computed tomography revealed sharply decreased
      cerebral blood flow, especially in the occipital area. Landau-Kleffner syndrome
      was suspected but a sleep electroencephalogram showed few abnormalities. He was
      started on clorazepate and diltiazem. A skin biopsy to rule out possible CLN2
      revealed, instead of the predicted curvilinear profiles, granular osmiophilic
      deposits, consistent with infantile neuronal ceroid lipofuscinosis (CLN1). The
      family reported increased seizure frequency and consulted with a colleague, who
      advised them to resume valproate and discontinue diltiazem. The boy died shortly
      thereafter. Decreased cerebral blood flow is a new finding in CLN1 with delayed
      onset. Calcium-channel blockers improve cerebral blood flow and perhaps delay
      clinical regression.

PMID- 11588995
TI  - Pre- and postnatal enzyme analysis for infantile, late infantile and adult
      neuronal ceroid lipofuscinosis (CLN1 and CLN2).
AB  - The recent development of simple, fluorogenic enzyme assays for infantile and
      late infantile neuronal ceroid lipofuscinosis (INCL and LINCL; CLN1 and CLN2) has
      greatly facilitated the diagnostic process for these diseases. In leucocytes and
      fibroblasts from INCL (n = 38) patients we found profound deficiencies of
      palmitoyl-protein thioesterase I (PPT1), the residual activity was < 5% of mean
      control activity. In fibroblasts from LINCL patients we found a similar
      deficiency of tripeptidyl-peptidase I activity (TPP-I), with < 2% activity in 16
      patients. The residual TPP-I activity in leucocytes from LINCL patients seemed
      substantially higher. We also showed the feasibility of reliable prenatal enzyme
      analysis. In five first-trimester and two second-trimester prenatal analyses for
      INCL, four affected foetuses were detected (PPT activity 3-6%). Two first
      trimester pregnancies at risk for LINCL were analysed and a clear TPP-I
      deficiency was detected in both cases (TPP-I activity 3-4%). The first patient
      with adult neuronal ceroid lipofuscinosis (ANCL) due to a deficiency of PPT is
      presented; her present age is 53 years and the onset of the disease was at 38
      years with psychiatric symptoms.

PMID- 11588996
TI  - Pre- and postnatal diagnosis of patients with CLN1 and CLN2 by assay of palmitoyl
      protein thioesterase and tripeptidyl-peptidase I activities.
AB  - Palmitoyl-protein thioesterase (PPT) and tripeptidyl-peptidase I (TPP-I)
      activities were measured in leucocytes and fibroblasts. Fourteen patients were
      confirmed as having late infantile neuronal ceroid lipofuscinosis due to a
      deficiency of TPP-I activity. This included one patient with a milder and more
      protracted form of the disease. In addition this enzyme deficiency was found in a
      clinically normal younger sibling of a patient. Of particular importance was the
      finding of normal TPP-I activity in two patients who had been diagnosed as having
      classical late infantile neuronal ceroid lipofuscinosis. A deficiency of PPT was
      confirmed retrospectively in stored fibroblasts from two patients who had already
      died having been diagnosed with infantile neuronal ceroid lipofuscinosis.
      Palmitoyl-protein thioesterase or TPP-I activities were measured in chorionic
      villi and cultured chorionic villi cells in three pregnancies. The enzyme results
      were confirmed by mutational analysis if the mutations were known, or, in the
      case of the pregnancy at risk for infantile neuronal ceroid lipofuscinosis by
      electron microscopy of the chorionic villi. Our results show that assay of PPT
      and TPP-I is reliable in the diagnosis of patients with mutations in the CLN1 and
      CLN2 genes. It is imperative to assay these enzymes in all patients to confirm
      the diagnosis and ensure accurate genetic counselling of other family members.
      Once an enzyme deficiency has been confirmed reliable prenatal diagnosis is
      available even if both mutations have not been detected.

PMID- 11588997
TI  - An Australasian diagnostic service for the neuronal ceroid lipofuscinoses.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are a family of related genetic
      disorders that together are believed to affect one child in every 12,500 births
      in the USA. Our laboratory has developed a diagnostic service for classical late
      infantile neuronal ceroid lipofuscinosis (LINCL) by assay of tripeptidyl
      peptidase I (TPP-I) activity using the fluorogenic peptide substrate Ala-Ala-Phe
      aminomethylcoumarin, followed by a screen for three mutations in the CLN2 gene.
      In addition, we have also begun to offer a limited diagnostic service for the
      juvenile (JNCL) and infantile (INCL) forms of the disease on the basis of
      mutation analysis of the CLN3 and CLN1 genes, respectively. Retrospective
      analysis of Australasian patients with a clinical suspicion of NCL has revealed
      that six are affected by LINCL, six by JNCL and, to date, two by INCL. Mutation
      analysis of our LINCL patients has shown that the three screened mutations,
      namely, the nonsense mutation R208X and the splice mutations IVS5-1 G > C and
      IVS5-1 G > A, constitute 83% of alleles.

PMID- 11588999
TI  - Hippocampal lesions in the neuronal ceroid lipofuscinoses.
AB  - Epilepsy is a common manifestation in all childhood-onset forms of neuronal
      ceroid lipofuscinosis. In order to document hippocampal lesions and their
      relationship to epilepsy we studied autopsy specimens from the hippocampi of a
      series of patients with the infantile (CLN1), classic late infantile (CLN2),
      Finnish variant late infantile (CLN5), and juvenile (CLN3) neuronal ceroid
      lipofuscinosis as well as Northern epilepsy (CLN8), using a battery of
      histological and immunocytochemical staining methods. Despite striking
      differences in the overall degree of neocortical neuronal storage and loss, these
      genetically heterogeneous forms of neuronal ceroid lipofuscinosis showed a common
      lesional pattern in the hippocampi: a relative sparing of the CA1 sector and
      severe involvement of the neighbouring CA2 sector, with intermediate degrees of
      involvement of the CA3 and CA4 sectors. These findings distinguish the
      hippocampal pathology associated with the neuronal ceroid lipofuscinoses from
      classical 'mesial temporal sclerosis' and show that the selective lesional
      pattern in the neuronal ceroid lipofuscinoses is not a secondary anoxic-ischaemic
      phenomenon. It is rather a consequence of the primary metabolic defects and may
      be directly involved in the causation of the epileptic discharges.

PMID- 11588998
TI  - Morphological studies on CLN2.
AB  - Electron microscopic, fluorescence microscopic, and immunohistochemical studies
      earlier performed on archival cerebral tissue from Max Bielchowsky's original
      three patients revealed curvilinear bodies rich in subunit C of mitochondrial ATP
      synthase (SCMAS). Recent progress in the elucidation of CLN2, i.e. identification
      of the defective lysosomal enzyme tripeptidyl-peptidase I (TPP-I) and mutations
      in the CLN2 gene have further corroborated earlier data. Immunohistochemically
      the absence of the TPP-I protein could be confirmed in the archival tissues using
      pathological controls. Unlike biochemistry, immunohistochemistry enables
      examination of these archival tissues elucidating the causative defect.
      Complementary molecular studies identified mutations in the CLN2 gene in the
      archival tissues and thereby convincingly demonstrated that these three children
      truly had classic late infantile neuronal ceroid lipofuscinosis (LINCL), now
      called CLN2. This archival study documents the possibilities to revalidate
      disease-specific original nosologic reports. Chloroquine is toxic to lysosomal
      enzymes and results in lysosomal storage. The material is autofluorescent and
      gives the ultrastructural pattern of curvilinear profiles, thus resembling
      classic late infantile NCL, representing a good experimental model. In humans
      chloroquine therapy may cause a myopathy (and retinopathy) and, as recently
      suggested, an encephalopathy marked by lysosomal accretion in several cell types
      including neurons. Immunohistochemically, SCMAS also accumulates, further
      strengthening morphologic similarity between LINCL and human chloroquine
      intoxication.

PMID- 11589000
TI  - Turkish variant late infantile neuronal ceroid lipofuscinosis (CLN7) may be
      allelic to CLN8.
AB  - One variant form of late infantile neuronal ceroid lipofuscinosis (LINCL) is
      found predominantly within the Turkish population (CLN7). Exclusion mapping
      showed that CLN7 was not an allelic variant of known NCL loci (CLN1, CLN2, CLN3,
      CLN5 or CLN6). Using the method of homozygosity mapping, a genome-wide search was
      undertaken and a total of 358 microsatellite markers were typed at an average
      distance of about 10 cM. A region of shared homozygosity was identified on
      chromosome 8p23. This telomeric region contained the recently identified CLN8
      gene. A missense mutation in CLN8 causes progressive epilepsy with mental
      retardation (EPMR) or Northern epilepsy, which has so far been reported only from
      Finland and is now classified as an NCL. The mouse model mnd has been shown to
      carry a 1 bp insertion in the orthologous Cln8 gene. Statistically significant
      evidence for linkage was obtained in this region, with LOD scores > 3, assuming
      either homogeneity or heterogeneity. Flanking recombinants defined a critical
      region of 14 cM between D8S504 and D8S1458 which encompasses CLN8. This suggests
      that Turkish variant LINCL, despite having an earlier onset and more severe
      phenotype, may be an allelic variant of Northern epilepsy. However mutation
      analysis has not so far identified a disease causing mutation within the coding
      or non-coding exons of CLN8 in the families. The Turkish variant LINCL disease
      causing mutation remains to be delineated.

PMID- 11589001
TI  - Cardiac pathology in neuronal ceroid lipofuscinoses--a clinicopathologic
      correlation in three patients.
AB  - We report the clinical details and the pathology of the heart at autopsy of three
      neuronal ceroid lipofuscinosis (NCL) patients. Two patients were diagnosed as
      classical juvenile NCL and one as a variant juvenile NCL (JNCL) with granular
      osmiophilic deposits (GRODs). Cardiac findings during life were retrospectively
      evaluated and included left ventricular hypertrophy with repolarization
      disturbances (ECG findings) in two patients with classical JNCL and severe
      bradycardia with periods of sinus arrest in one of them, severe supraventricular
      tachycardias during anaesthesia in the variant JNCL-patient. At autopsy
      myocardial and valvular storage of lipopigments, diagnostic for NCL, was observed
      histologically and confirmed ultrastructurally in all three cases. In two
      patients with JNCL the storage was associated with hypertrophy and dilation of
      both ventricles, degenerative myocardial changes, interstitial fibrosis and fatty
      replacement. Abundant accumulation and degeneration were seen in all components
      of the conduction system in three patients, which outreached at several places by
      far the storage of the adjacent myocardium. Our observations indicate a prominent
      involvement of the heart in NCL, with preference of storage for the conduction
      system of the heart.

PMID- 11589002
TI  - Analysis of candidate genes in the CLN6 critical region using in silico cloning.
AB  - CLN6, the gene for variant late infantile neuronal ceroid lipofuscinosis, was
      mapped to a 4 cM region on chromosome 15q22-23. Subsequently the critical region
      was narrowed to less than 1 cM between microsatellite markers D15S988 and
      D15S1000 by additional marker typing in an expanded family resource. A physical
      map was constructed across this region using YAC and PAC clones and sequence was
      generated from two PAC clones. This sequence was analysed together with
      overlapping sequence generated by the Human Genome Project to identify genes
      within the region using an in silico cloning approach. In all, 29 genes have been
      identified and 18 have been analysed for mutations by direct sequencing. This
      powerful new approach will lead to the identification of CLN6.

PMID- 11589003
TI  - Batten disease research--where we were--where we are--where we are going.

PMID- 11589004
TI  - Fine mapping of ovine ceroid lipofuscinosis confirms orthology with CLN6.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases with
      severe neurodegenerative pathology. An ovine model (OCL) has well defined
      parallels with the human disease at a biochemical and pathological level. The
      gene for OCL is located in the chromosomal region OAR 7q13-15. This region is
      syntenic with HSA 15q21-23 suggesting that OCL and CLN6 represent mutations in
      orthologous genes. New microsatellite markers were used for refinement of the OCL
      critical region. YAC clones that span the critical region have been isolated and
      comparative gene mapping confirms that the regions for CLN6 and OCL are
      equivalent.

PMID- 11589005
TI  - Neuronal ceroid lipofuscinosis in Australian Merino sheep: a new animal model.
AB  - In 1997, neuronal ceroid lipofuscinosis (NCL) was identified for the first time
      in Merino sheep in Australia. A homozygosity mapping approach localized the
      disease gene in Merino sheep to the same region on chromosome 7 in which NCL was
      recently mapped in South Hampshire sheep. This region shows conserved synteny
      with the region on human chromosome 15 in which the human late infantile NCL
      variant CLN6 was mapped. NCL in Merino and South Hampshire sheep are therefore
      potential animal models for the human late infantile variant CLN6.

PMID- 11589006
TI  - Congenital ovine neuronal ceroid lipofuscinosis--a cathepsin D deficiency with
      increased levels of the inactive enzyme.
AB  - We recently showed that a form of neuronal ceroid lipofuscinosis (NCL) in white
      Swedish landrace sheep is caused by a missense mutation in the cathepsin D gene
      resulting in complete inactivation of the enzyme. Despite the lack of cathepsin D
      activity, the brains of the cathepsin D deficient sheep showed strongly increased
      staining for cathepsin D in immunohistochemistry. By Western blotting, a 5-10
      fold increase in the level of cathepsin D was confirmed. These results indicate
      that the missense mutation in congenital NCL sheep results in the synthesis of an
      inactive yet stable cathepsin D.

PMID- 11589007
TI  - Infantile neuronal ceroid lipofuscinosis: no longer just a 'Finnish' disease.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are a group of enigmatic
      neurodegenerative disorders of children that have in common the storage of
      autofluorescent lipofuscin, or aging pigment, in the brain. With the
      identification of the three major genes involved in the disorder, the NCLs are
      now appreciated to represent true lysosomal storage disorders. The most severe
      (infantile) form of NCL is caused by mutations in a lysosomal thioesterase that
      removes fatty acids from modified cysteine residues in proteins. Although the
      disorder was first described in Finland (and the identification of the underlying
      gene (CLN1) made in this population) defects in CLN1 and the underlying
      deficiency have been widely reported outside of Scandinavia. In this report, we
      summarize the relationship of genotype to phenotype in the disorder and evaluate
      known mutations in light of the recently solved crystal structure of defective
      enzyme, palmitoyl-protein thioesterase (PPT). We also discuss progress in
      identifying the fatty acyl cysteine thioesters that accumulate in PPT deficiency
      and in working toward animal models of NCL. Recent progress in these areas holds
      promise for the eventual treatment of the disorder.

PMID- 11589008
TI  - Role of palmitoyl-protein thioesterase in cell death: implications for infantile
      neuronal ceroid lipofuscinosis.
AB  - Infantile neuronal ceroid lipofuscinosis (INCL) is a childhood neurodegenerative
      disease caused by the selective death of cortical and retinal neurons as the
      result of an inherited palmitoyl-protein thioesterase 1 (PPT1) deficiency.
      Neuronal death is common to many lysosomal storage diseases but it occurs very
      early in INCL and we show here that inhibition of PPT1 increases the
      susceptibility of these cells to apoptotic cell death. Thus transient
      transfection of LA-N-5 neuroblastoma cells with a reverse-oriented (antisense)
      PPT1 (AS-PPT1) reduced PPT1 enzyme activity (as measured by an in vitro assay)
      and increased the susceptibility to apoptosis induced by C2 ceramide. Similarly,
      inhibition of PPT1 with a synthetic inhibitor (AcG-palmitoyl diaminoproprionate
      VKIKK) (DAP1) (100 microM) increased the susceptibility of the cells to apoptosis
      induced by either C2-ceramide or etoposide and Adriamycin (doxorubicin), common
      chemotherapeutic agents used in the treatment of solid tumours. In contrast,
      overexpression of PPT1 led to increased resistance to cell death induced by these
      drugs.

PMID- 11589009
TI  - Aminoglycoside-mediated suppression of nonsense mutations in late infantile
      neuronal ceroid lipofuscinosis.
AB  - The ability of aminoglycoside antibiotics to promote readthrough of eukaryotic
      stop codons has attracted interest in these drugs as potential therapeutic agents
      in human disorders caused by nonsense mutations. One disease for which such a
      therapeutic strategy may be viable is classical late infantile neuronal ceroid
      lipofuscinosis (LINCL), a fatal childhood neurodegenerative disorder with
      currently no effective treatment. Premature stop codon mutations in the gene CLN2
      encoding the lysosomal tripeptidyl-peptidase 1 (TPP-I) are associated with
      disease in approximately half of children diagnosed with LINCL. The aim of this
      study was to examine the ability of the aminoglycoside gentamicin to restore TPP
      I activity in LINCL cell lines. In one patient-derived cell line that was
      compound heterozygous for a commonly seen nonsense mutation, Arg208Stop and a
      different rare nonsense mutation, approximately 7% of normal levels of TPP-I were
      maximally restored with gentamicin treatment. In other cell lines from patients
      that were compound heterozygous for Arg208Stop and a splice junction mutation,
      approximately 0.5% of maximal activity was restored. These results suggest that
      pharmacological suppression of nonsense mutations by aminoglycosides or
      functionally similar pharmaceuticals may have therapeutic potential in LINCL.

PMID- 11589010
TI  - Specific substrate for CLN2 protease/tripeptidyl-peptidase I assay.
AB  - The classic late infantile neuronal ceroid lipofuscinosis (LINCL, CLN2) is a
      fatal neurodegenerative disorder that results from mutations in a gene encoding a
      lysosomal proteinase, known as CLN2 protease (CLN2p) or tripeptidyl peptidase I
      (TPP-I). Three different substrates, fluorescein isothiocyanate-labelled
      haemoglobin, A-F-F-7-amino-4-methylcoumarin (AAF-AMC) and G-F-F-L-7-amino-4
      trifluoromethylcoumarin (GFFL-AFC) have been used for the CLN2p/TPP-I assay with
      varying degrees of residual activities in patients with LINCL. Further,
      conclusive identification of carriers are not possible with the first two
      substrates. An assay for the CLN2p/TPP-I based on the cleavage of amino terminal
      tripeptide from G-F-F-L-AFC was applied to prenatal and postnatal diagnosis of
      LINCL patients and heterozygote carriers. In leukocytes, the CLN2p/TPP-I
      activities in controls and heterozygote carriers were 1995 +/- 154 (n = 15) and
      918 +/- 253 (n = 15) nmol/h/mg protein respectively. No CLN2p/TPP-I activity was
      detectable in all but two patients. These two patients had less than 2% residual
      activity, and had delayed clinical symptoms for LINCL. This shows that the G-F-F
      L-AFC is a highly specific substrate for the CLN2p/TPP-I assay. The fact that
      with this substrate the enzyme cleaves a peptide bond between the two amino acids
      may be the reason for the high level of specificity.

PMID- 11589011
TI  - The substrate range of tripeptidyl-peptidase I.
AB  - Tripeptidyl-peptidase I (TPP-I) is an exopeptidase which removes tripeptides from
      the N-terminus of peptides. Mutations in TPP-I are responsible for late infantile
      neuronal ceroid lipofuscinosis (CLN2). The nature of the physiological substrates
      and the range and specificity of the enzyme are unclear. Previous experiments
      suggest that the enzyme can degrade small peptides but not proteins. Digestion of
      a range of peptides of different size by TTP-I suggests that the enzyme will
      degrade small peptides with an extended N-terminal domain but not structured
      peptides. In general, this cut-off occurs between masses of 4.5 kDa and 6 kDa.
      Reference to the structures of other peptidases suggests a mechanism for this
      size selectivity.

PMID- 11589012
TI  - New mutations in the neuronal ceroid lipofuscinosis genes.
AB  - Thirty-eight mutations and seven polymorphisms have recently been reported in the
      genes underlying the neuronal ceroid lipofuscinoses (NCLs) including 11 new
      mutations described here. A total of 114 mutations and 28 polymorphisms have now
      been described in the five human genes identified which cause NCL. Thirty-eight
      mutations are recorded for CLN1/PPT; 40 for CLN2/TTP-1, 31 for CLN3, four for
      CLN5, one for CLN8. Two mutations have been described in animal genes (cln8/mnd,
      CTSD). All mutations in NCL genes are contained in the NCL Mutation Database
      (http://www.ucl.ac.uk/NCL).

PMID- 11589013
TI  - Tripeptidyl-peptidase I in neuronal ceroid lipofuscinoses and other lysosomal
      storage disorders.
AB  - The classic late infantile form of neuronal ceroid lipofuscinosis (CLN2, cLINCL)
      is associated with mutations in the gene encoding tripeptidyl-peptidase I (TPP
      I), a lysosomal aminopeptidase that cleaves off tripeptides from the free N
      termini of oligopeptides. To date over 30 different mutations and 14
      polymorphisms associated with CLN2 disease process have been identified. In the
      present study, we analysed the molecular basis of 15 different mutations of TPP-I
      by using immunocytochemistry, immunofluorescence, Western blotting, enzymatic
      assay and subcellular fractionation. In addition, we studied the expression of
      TPP-I in other lysosomal storage disorders such as CLN1, CLN3,
      muccopolysaccharidoses and GM1 and GM2 gangliosidoses. Our study shows that TPP-I
      is absent or appears in very small amounts not only in cLINCL subjects with
      mutations producing severely truncated protein, but also in individuals with
      missense point mutations, which correlates with loss of TPP-I activity. Of
      interest, small amounts of TPP-I were detected in lysosomal fraction from
      fibroblasts from cLINCL subject with protracted form. This observation suggests
      that the presence of small amounts of TPP-I in lysosomes is able to delay
      significantly CLN2 disease process. We also show that TPP-I immunoreactivity is
      increased in the brain tissue of CLN1 and CLN3 subjects, stronger in glial cells
      and macrophages than neurons. Less prominent increase of TPP-I staining was found
      in muccopolysaccharidoses and GM1 and GM2 gangliosidoses. These data suggest that
      TPP-I participates in lysosomal turnover of proteins in pathological conditions
      associated with cell/tissue injury.

PMID- 11589014
TI  - CLN3 disease process: missense point mutations and protein depletion in vitro.
AB  - Although the CLN3 gene associated with the disease process in subjects with the
      juvenile form of neuronal ceroid lipofuscinosis was discovered in 1995, our
      knowledge of the physiological function of its gene product, CLN3 protein, is
      still incomplete. To gain more insight into the structural properties and
      function of CLN3 protein we studied at present: i) how the naturally occurring
      point mutations Arg334Cys and Leu101Pro affect the biological properties of CLN3
      protein, and ii) whether depletion of CLN3 protein synthesis by using an
      antisense approach induces a distinct phenotype in cells of neuronal origin in
      vitro. Here we report that although both CLN3 mutant proteins are targeted to
      lysosomes, thus similar to wild-type CLN3 protein, they are devoid of the
      biological activity of wild-type CLN3 protein such as its effect on lysosomal pH
      or intracellular processing of amyloid-beta protein precursor and cathepsin D in
      vitro. The Leu101Pro mutation affected significantly the maturation and stability
      of CLN3 protein. The Arg334Cys mutation influenced mildly the maturation and
      turnover of CLN3 protein, but at the same time abolished the function of CLN3
      protein in vitro, which suggests that the Arg334 may constitute a part of the
      active site of CLN3 protein. In addition, we show that depletion of CLN3 protein
      synthesis in human neuroblastoma cells in vitro induces outgrowth of long
      cellular processes and formation of cellular aggregates and affects the viability
      of these cells. This finding suggests that CLN3 protein is implicated in
      biological processes associated with the differentiation of cells of neuronal
      origin.

PMID- 11589015
TI  - Analysis of CLN3-protein interactions using the yeast two-hybrid system.
AB  - Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a childhood
      neurodegenerative disease that is caused by mutations in the CLN3 gene. The
      protein encoded by CLN3 has no homology with any proteins of known function and
      its cellular role remains elusive. In order to investigate the role played by the
      CLN3 protein we aimed to identify interacting proteins. Here, we describe the
      yeast two-hybrid system as the approach taken to investigate such protein-protein
      interactions. CLN3 was expressed as a fusion protein with a DNA-binding domain
      and used to screen a library of human fetal brain cDNAs fused to a
      transcriptional activation domain. Owing to low level expression of the full
      length CLN3 fusion protein, truncated regions corresponding to the predicted
      hydrophilic regions were also tested. No proteins that interact with CLN3 were
      detected, nor was there any evidence for CLN3-CLN3 interactions. Potential
      interaction of CLN3 with subunit c of mitochondrial ATP synthase, the major
      component of the storage material that accumulates in Batten disease patients,
      was also tested. No interaction was detected suggesting that the accumulation of
      subunit c does not result from loss of a process that requires a direct
      interaction with CLN3. We conclude that either CLN3 does not interact with other
      proteins or such interactions cannot be detected using the two-hybrid system.

PMID- 11589016
TI  - Searching for interacting partners of CLN1, CLN2 and Btn1p with the two-hybrid
      system.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are the most common neurodegenerative
      disorders of childhood. The CLN1, CLN2 and CLN3 genes are associated to the
      infantile, late infantile and juvenile forms of NCL, respectively. We have
      subcloned the cDNAs encoding CLN1, CLN2 and BTN1, the yeast homologue of human
      CLN3, into plasmid vectors to evaluate whether these proteins interact with other
      proteins co-expressed from either a cDNA library derived from human cerebellum or
      from yeast, respectively, using the two-hybrid system. We concluded that CLN1
      most likely does not interact with any other proteins in vivo. Furthermore, it is
      unlikely that CLN2 interacts with other proteins in vivo, although this study
      utilized a cDNA encoding the CLN2 precursor and it is possible that interacting
      partners may be excluded by the nature of this protein structure. Finally, we
      conclude that proteins that interact with Btn1p and therefore CLN3 cannot be
      identified using the whole proteins in a two-hybrid system, due to the
      hydrophobic nature of this protein. By understanding the topology of CLN3,
      specific regions of CLN3 need to be tested by two-hybrid to identify any
      interacting partners.

PMID- 11589017
TI  - CLN-3 protein is expressed in the pancreatic somatostatin-secreting delta cells.
AB  - Juvenile neuronal ceroid lipofuscinosis (JNCL) is a severe autosomal recessive
      neurodegenerative disorder resulting from mutations in the CLN3 gene. The gene
      product is a 438-amino acid hydrophobic peptide of unknown function containing
      five transmembrane domains. In order to study the tissue distribution of the
      peptide, polyclonal antibodies were raised in rabbits to three epitopes and were
      affinity purified before use. All three antibodies were used together for
      immunocytochemical staining of human pancreas. This staining showed localization
      in pancreatic islet cells. Double labelling of the tissue indicated that cells
      staining for the CLN3 protein were also positive for somatostatin.

PMID- 11589018
TI  - [Electro-impulse therapy in combined treatment of patients with thyrotoxic goiter
      complicated by cardiac fibrillation].
AB  - Cardiac fibrillation was revealed at admission in 260 (5.2%) of 4996 patients who
      were to undergo subtotal resection of thyroid gland for toxic goiter. In 114
      (43.8%) patients sinus rhythm was restored with drugs in preoperative period.
      Electroimpulse therapy was carried out in other 146 patients which was effective
      in 89% cases. Efficacy of electroimpulse therapy depended mainly on the
      arrhythmia duration. Restoration of sinus rhythm before operation in patients
      with toxic goiter improves conditions of preoperative preparation and decreases
      the risk of surgical treatment. There were no lethal outcomes.

PMID- 11589019
TI  - [Method of surgical treatment of the thyroid gland from mini-approach].
AB  - Two variants of mini-approach 2 cm long were developed. They permitted to perform
      safe 39 various operations on thyroid gland with favorable short- and long-term
      results. The procedure may include recurrent nerve imaging. Binocular vision is
      necessary. Using this technique, unilateral lobectomy with isthmus removal for
      solitary and multinodular unilateral goiter was performed in 15 patients,
      bilateral subtotal lobectomies--in 18 patients with bilateral nodular goiter.
      Bilateral lobectomy (thyreoidectomy) was performed in 6 patients because of
      advanced disease.

PMID- 11589020
TI  - [Prevention of postoperative hypothyroidism in surgical treatment of diffuse
      toxic goiter].
AB  - Experience of treatment of more than 1000 patients with diffuse toxic goiter
      (DTG) is presented. Complex of measures performed before and after operation for
      reduction of hypothyroidism rate is developed. Histology examination during
      operation permits to determine volume of residual thyroid tissue. Local
      laserotherapy improves long-term results of surgical treatment. Rate of
      postoperative hypothyroidism in patients with DTG has decreased from 43.6 to
      3.3%.

PMID- 11589021
TI  - [Differential diagnosis of renal colic].
AB  - Potential of modern examinations in differential diagnosis of renal colic and
      other emergency states is considered. Renal ultrasonography permits in the
      majority of cases to make diagnosis based on dilatation of caliceal-pelvic
      system, sometimes with detection of obstruction cause. It is necessary to
      differentiate parapelvical cysts from dilatation of caliceal-pelvic system,
      therefore pharmacultrasonic examination of the kidneys with lasix is recommended.
      Color dopplerography of the urinary bladder with detection of urine ejection from
      ureters ostia is analogue of conventional invasive diagnostic method-
      chromocystoscopy. Magnetic-resonance urography is updated non-invasive, non
      contrast and non-radiation method of diagnosis of urinary tract dilatation.

PMID- 11589022
TI  - [Diagnosis and surgical treatment of internal biliary fistula].
AB  - Results of examination and surgical treatment of 172 patients with internal
      biliary fistula (IBF) are analyzed. IBF was revealed in 0.22% of hospitalized
      patients with cholelithiasis. There were 4 variants of fistula formation.
      Combined spontaneous multiple fistula were described for the first time in 8
      patients. Based on assessment of IBF's clinical symptoms formula for prediction
      of IBF development was proposed. Diagnostic potential of instrumental, X-ray,
      endoscopic and ultrasonic examinations was assessed. Differential surgical policy
      depending on IBF variant is described.

PMID- 11589023
TI  - [Features of surgical strategy in acute cholecystitis in old patients].
AB  - Results of treatment of 197 patients at the age of 75-years and older with acute
      cholecystitis in terms of active (early operations) and active-delaying (delayed
      and elective operations) policy were analyzed. It was established that changes of
      gall bladder wall in old patients with acute cholecystitis are of ischemic
      genesis, of primary-destructive and irreversible nature leading to gangrene and
      phlegmon of gall bladder wall in 84% cases. In 2/3 cases clinical picture doesn't
      reflect destructive nature of the disease. Severity of the patients state and its
      dynamics may be assessed most objectively by APACHE III. Conservative treatment
      doesn't prevent progress of destructive-inflammatory process and complications
      development. Cholecystectomy from laparotomy is the operation of choice in this
      group of patients. Early radical operation for acute cholecystitis in old
      patients permits to decrease postoperative lethality to 3.3%. The score of APACHE
      III at hospitalization is the criterion of the scope and terms of surgery. If
      APACHE III is more than 55 points, it is necessary to carry out complex
      preoperative correction of somatic disorders. Minimally invasive palliative
      operations are indicated for 10% patients of this category.

PMID- 11589024
TI  - [Reservoir ileorectal anastomosis].
AB  - It was established in experimental and clinical studies that creation of
      reservoir ileorectal anastomosis by standard methods is accompanied by hypotonia,
      lining deformation and transformation of mucosa: of terminal part of the ileum
      under the influence of "aggressive" rectal contents. Development of a great
      number of secretory elements and loss of basic part of resorption structures of
      small intestine mucosa are accompanied by chronic postcolectomic diarrhea. Method
      of creation of reservoir ileorectal anastomosis with areflux mechanism was
      developed for correction of these disorders. Results of experimental studies on
      33 dogs and 5 clinical cases demonstrate that the areflux mechanism coordinates
      motor-evacuatory intestinal function after colectomy and impedes development of
      specific pathomorphologic changes of mucosa of reservoir ileorectal anastomosis.
      This is the main condition for repair of fecoformation in patients in remote
      period after colectomy.

PMID- 11589025
TI  - [Surgical treatment of ischemic heart disease by transmyocardial laser
      revascularization].
AB  - Results of transmyocardial laser revascularisation (TMLR) of the myocardium are
      analyzed. Two types of laser equipment were used domestic laser high-energy CO2
      synchronized with patient's ECG, and XeCl laser Max-20. 32 patients underwent
      TMLR as a single method of surgical correction of the disease, 15 in combination
      with other methods of myocardium revascularisation. Obtained data testify that
      TMLR is a highly effective procedure in selective patients with IHD. Results
      confirm necessity of differential surgical policy for ischemic heart disease that
      permits to use adequate method of myocardium revascularisation for each patient.

PMID- 11589026
TI  - [Surgical tactics in combined gunshot wounds of the pelvis].
AB  - Based on experience of treatment of 177 wounded with gunshot combined wounds of
      the pelvis, rational surgical policy in these wounds is substantiated. It is
      necessary to maintain sequence of each stage of the operation bearing in mind
      trajectory of shell in organs and tissues of the abdomen and pelvis, simultaneous
      wounds of organs which are significantly different by specific anatomic structure
      and physical role.

PMID- 11589027
TI  - [Optimization of surgical treatment of suppurative-necrotic lesions of the foot
      in patients with diabetes mellitus].
AB  - The analysis of treatment results in 559 patients with diabetes mellitus
      complicated by foot pyonecrotic lesions was carried out. Surgical treatment was
      performed in 448 patients considering route of infection spread (basic group),
      conventional methods of treatment were used in 111 patients (control group). It
      is shown that one of the causes of unsuccessful treatment results was the
      infection spread from foot to leg by toes tendons and synovial sheaths. The study
      of microbial contamination in wound exudate, distal and proximal sites of tendons
      revealed a significant difference in proximal-distal gradient for aerobes (2.8 +/
      0.19 lg/g) and anaerobes (1.71 +/- 0.16 lg/g, p < 0.01). Methods of surgical
      treatment of foot pyonecrotic lesions allowing for route of infection in patients
      with diabetes mellitus were developed. Use of these methods allowed to decrease
      more than 2 times the number of femoral amputations, and to increase the rate of
      surgical interventions with salvage of limb's support function from 71.2 to
      87.7%.

PMID- 11589028
TI  - [Surgery of communicating veins of the leg in complicated varicose disease].
AB  - Comparative analysis of elimination of blood regurgitation via crus communicant
      veins in varicose disease complicated by trophic disorders (lipodermal sclerosis
      and trophic ulcers) was carried out in two groups of patients. In groups 1(120
      cases) routine Cocett's and Linton's operations with long stripping of venous
      trunks were performed. In group 2 (68 cases) minimally-invasive methods--distant
      communicantectomy and partial stripping--were used. Surgical techniques, short-
      and long-term results are described. In group 1 there were 26.6% of wound
      complications and 60% of crus neuropathies in remote period. In 2 group
      operations were performed 4 times faster, with insignificant blood loss,
      accompanied by primary adhesion and early discharge of patients. Period of
      temporary disability in these patients was less than in group 1, rate of
      neuropathies was 5.8%.

PMID- 11589029
TI  - [Ectopy of the pancreas in the stomach with development of decompensated
      stenosis].

PMID- 11589030
TI  - [New method of colorectal anastomosis in children with Hirschsprung disease].
AB  - Developed method of treatment of Hirschsprung's disease lies in removal of
      injured part of the intestine and establishment of oblique termino-terminal
      colorectal anastomosis between pull through colon and rectum resected from
      parasacral-perineal approach. Proposed method ensures complete removal of
      aganglionar site, favorable conditions for anastomosis and healing that decrease
      probability of postoperative complications. Operation was performed in 7
      patients. There were no immediate and remote complications.

PMID- 11589031
TI  - [Pancreas as one of the targets of "auto-enzyme explosion" in pancreatitis].
AB  - The authors consider pancreatitis not as a nosological unity but as a clinical
      manifestation of enzymatic or autoenzymatic aggression. Based on clinical,
      histopathomorphological examinations, the authors describe pancreatogenous
      enzymatic injury of organs and tissues (pancreas, heart, kidneys, liver,
      gastrointestinal tract, etc). For 4-8 days to 2-10 years the syndrome may damage
      not only pancreatic parenchyma, but also vascular structures with formation of
      general vasculitis, lymphangitis and subsequent thrombotic microangiopathy. The
      authors regard pancreas as one of the target organs--of general disease, in which
      serious injuries of other organs and tissues may prevail over changes in the
      primary zone of aggression.

PMID- 11589032
TI  - [Carotid endarterectomy under local anesthesia].
AB  - Results of carotid endarterectomy (CEAE) in 193 patients with different degree of
      cerebrovascular insufficiency were analyzed. All the patients were men with
      carotid atherosclerosis (age from 39 to 68 years, mean age 53.6 +/- 0.4). A total
      of 253 CEAEs were performed under local anesthesia (60 patients underwent
      consecutive bilateral operations). In early postoperative period 3 patients died,
      one of them--of ischemic stroke due to thrombosis of internal carotid artery on
      the side of the operation. Non-fatal stroke was in 1 patient. There were no
      intraoperative cerebral complications. This testifies to reliability of cerebral
      circulation control through direct contact with patient.

PMID- 11589033
TI  - Age-adjusted death rates: trend data based on the year 2000 standard population.
AB  - Age-adjusted death rates are routine mortality risk measures used to compare
      rates over time or between groups such as those living in different geographic
      areas. This type of measure eliminates differences that would be caused because
      one population is older than another. Beginning with mortality data for 1999, the
      standard population used by the Centers for Disease Control and Prevention's
      National Center for Health Statistics (NCHS) to calculate age-adjusted death
      rates based on the Year 2000 estimated population distribution replacing that of
      1940 used previously. Comparisons of 1999 mortality data with that of 1998 and
      earlier years cannot be made unless age-adjusted death rates are based on the
      same standard population. Changing the standard population generally changes the
      magnitude of an age-adjusted death rate and may change the magnitude of the
      differential between two groups. Typically, the change in standard makes
      relatively little difference in the mortality trend but it can when age-specific
      rates have divergent patterns. This publication provides age-adjusted death rates
      by race and sex based on the year 2000 population standard and directs readers to
      the NCHS Web site for age-adjusted death rates by selected causes.

PMID- 11589034
TI  - Leprosy.

PMID- 11589035
TI  - HIPAA privacy rule: clearer guidance, cloudier future.
AB  - There will likely be many developments through the end of the year regarding the
      HIPAA Privacy Rule. Healthcare Leadership & Management Report will be talking to
      CEOs from around the country during September to learn what they are doing in
      their hospitals and health systems to prepare for the coming compliance deadline
      for both the standardized electronic transactions and the privacy standards. We
      will report on what we find in a fall issue. Readers are welcome to submit their
      own case studies or information on preparations for compliance to Lee Reeder,
      editor, by calling 909-338-0909 or by e-mail at editor@americangovernance.com.

PMID- 11589036
TI  - Patient safety update.

PMID- 11589038
TI  - [Radiosensitization effect of taxol on malignant tumor cells].
AB  - Radiosensitizating abilities of taxol have been investigated in vitro using L929
      cells and in vivo Geren carcinoma (T-8 cell line). Radiosensitizating effect of
      taxol was detected for the both cell lines. Pathologic mitoses have been also
      analyzed and increasing of abnormal mitosis total level was observed. It is
      supposed that this phenomenon could determine radiosensitizating abilities of
      taxol.

PMID- 11589037
TI  - [Gene protective effect of the short-chain derivative of Vitamin E under the
      action of alkylating compounds].
AB  - The gene protective effect of the short chain derivative of vitamin E was
      investigated in rats intoxicated with embichin and cyclophosphamide. Prophylactic
      administration of tocopherol derivative for 14 days promotes reduction of the
      genome and chromosome disturbances in marrow cells caused by this compounds.
      Correcting influence of tocopherol derivative depends on chemical structure and
      biologic peculiarities of the alkylating compound.

PMID- 11589040
TI  - [New morphological marker for chromosomes of the fourth homologous group of
      Triticinae].
AB  - The character "hairy leaf sheath" was studied in two groups of introgressive
      common wheat lines. The first group involves lines containing genetic material of
      Aegilops sharonensis, the second one includes lines with chromatin of Triticum
      miguschovae. The gene controlling hairy leaf sheath, Hs, was located by us on
      chromosomes 4S1 (Ae. sharonensis) and 4D (T. miguschovae) due to its joint
      transfer with beta-Amy-S(1)1, beta-Amy-D1, Acph-S(1)1 and Acph-D1 genes situated
      on the and 4D chromosomes. The possibility to use the identified gene as a
      morphological marker for these chromosomes was shown.

PMID- 11589039
TI  - [Changes of gene expression in Solanum tuberosum L. as a result of transgenes].
AB  - Potato plants of various cultivars, transformed using Agrobacterium tumefaciens
      with pGV941 plasmid, differed from control plants in glyphosate herbicide
      tolerance, tryptophane content, intensity of callusogenesis, microtuber formation
      in vitro and multimolecular forms of peroxidase (EC 1.11.1.7) and superoxide
      dismutase (EC 1.15.1.11). The results demonstrate the influence of alien DNA on
      structural gene expression in transgenic plants.

PMID- 11589041
TI  - [Assessment of phyto- and cytotoxic effects of heavy metals and aluminum
      compounds using onion apical root meristem].
AB  - The effects of different concentrations (10(-6)-10(-3) M) of salts of six metals
      (cadmium, lead, nickel, aluminum, copper, and zinc) on the root growth of onion
      (Allium cepa L.) seedling and cell division, chromosome and nucleus morphology in
      root tip cells were studied. The obtained results showed that tested compounds
      inhibit the root growth, reduce the mitotic activity of meristem cells and cause
      the chromosome and nucleus irregularities. On the basis of these data two rows of
      metal salt toxicity were proposed--for effective concentrations (EC50) of toxic
      action: CuSO4 > CdCl2 > NiSO4 > Pb(CH3COO)2 > Al(NO3)3 > ZnSO4, and for sublethal
      and lethal effects of investigated substances: CuSO4 > Pb(CH3COO)2 > CdCl2 >
      ZnSO4 > NiSO4 > Al(NO3)3.

PMID- 11589042
TI  - [Use of PCR for detection of maize seeds infected with the fungus Fusarium
      moniliforme Sheldon var.lactis].
AB  - The procedure of the PCR for the detection of Fusarium moniliforme Sheldon var.
      lactis on the maize seeds has been elaborated. The based on a highly sensitive
      molecular genetics technology method of fungal pathogen detection allows to
      reveal its presence before the visual symptoms of seed damage.

PMID- 11589043
TI  - [Seed set analysis in three amaranth species (A. cruentus, A. caudatus, and A.
      lividus) under self- and cross-pollination conditions].
AB  - Seed set was analyzed in three amaranth species (A. cruentus, A. caudatus, and A.
      lividus) under conditions of self- and cross-pollination during four vegetative
      periods in 1995-1998. It was demonstrated, that the populations of these species
      are polymorphic for the breeding system and that they consist of self-sterile and
      self-fertile plants. The populations were composed mostly of self-sterile plants
      and the percentages of self-fertile plants were only 34.7%, 18.7%, and 12.5% for
      A. cruentus, A. caudatus, and A. lividus respectively. The level of self
      fertility was high in the first year of isolation, it sharply decreased during
      the subsequent years of selfing, due to inbreeding effect. Seed set under self-
      and cross-pollination is determined by species-specificity of the plants,
      influence of conditions of their growth, and inbreeding depression. Conditions of
      growth had the strongest influence on seed set. Index of its influence varied
      from 0.53 to 0.87 for the cross-pollinated plants and from 0.13 to 0.68 for the
      self-pollinated ones. Analysis of variance demonstrated a weak effect of the
      interaction of these factors. Spearman's rank correlation demonstrated a highly
      significant agreement between the seed set values for the self- and cross
      pollinated plants of A. cruentus and A. lividus. The lines derived from the three
      amaranth species varied widely in the seed set values under both self- and cross
      pollination conditions.

PMID- 11589044
TI  - [Use of isoenzymes for the identification of apricot cultivars].
AB  - Isozyme polymorphism was used for identification of apricot cultivars. 34
      cultivars of 38 studied ones had unique genotype profiles for allelic composition
      of the AAT-1, EST-1, EST-2, SOD-1, LAP-1, PX-2 loci and AMY phenotypes. All
      regionized and being under State sort testing cultivars of hybridous origin were
      differentiated. Cultivars of clonal selection were identified regarding cultivars
      type.

PMID- 11589045
TI  - Phylogenetic relationships of three species of crows (Corvidae, Aves) based on
      the restriction site variation of nuclear ribosomal RNA gene.
AB  - Southern blot analysis of nuclear ribosomal DNA (rDNA) was carried out to examine
      phylogenetic relationships between three species of crows: Corvus cornix, C.
      corone and C. macrorhynchos. In this purpose DNA samples of birds were digested
      by 12 restriction enzymes (EcoRI, HindIII, PstI, BamHI, DraI, PvuII, KpnI, XbaI,
      BglII, BclI, SacI and AatI) and hybridized with the clones of mouse rDNA probes
      (18S, 28S and INT). Based on the data obtained and Gallus gallus restriction map
      as a standard the restriction site maps of the main rDNA repeating unit types
      (repetypes) were constructed. The length of crow rDNA genes was estimated to be
      22.5 kb for Jungle and 22.0 kb for Hooded and Carrion crows. C. corone and C.
      cornix shared a common repetype which differed, by presence of two restriction
      sites (XbaI and PvuII) in the spacer region, from that of C. macrorhynchos with
      the estimated sequence divergence of 0.26%. Restriction-size variation was
      revealed between individuals of C. corone and C. cornix, although the substantial
      meanings of this variation remain unclear yet. These data suggest that the crow
      species evolve with slower rate of molecular evolution, as generally observed in
      other avian species, compared with the higher extent in external morphology,
      ecological features and behavior.

PMID- 11589046
TI  - Polymorphism of molecular-genetic systems in the Polish red cattle.
AB  - The object of this study was to investigate gene polymorphism in the Polish Red
      (PR) cattle, a local Polish breed included in the FAO conservation programme.
      Milk protein genes and other genes with possible effect on production traits were
      analysed. Frequencies of different gene variants were compared with those in the
      Polish Friesian cattle. The following gene polymorphisms were analysed with
      PCR/RFLP technique: milk protein genes--kappa-casein and beta-lactoglobulin,
      growth hormone (GH), PitI (a transcription factor) and leptin. Moreover, SSCP
      analysis was performed of myostatin (MSTN) gene at the site previously shown to
      cause muscle overgrowth in Belgian Blue double-muscled cattle. A significant
      difference was found in this study between kappa-casein A and B allele frequency
      in PR and Friesian cattle. No such differences were found in the frequency of A
      and B alleles of beta-lactoglobulin, L and V alleles of GH, A and B alleles of
      PitI, and A, B and C alleles of leptin gene. In the analysed group of the Polish
      Red cattle three animals were found with the rare AI genotype of -lactoglobulin.
      No such genotype was identified in analysed Friesians. Moreover, 8 PR animals
      were identified carrying a mutation in MSTN gene, possibly identical to that
      causing the double-muscled phenotype in some breeds of meat cattle.

PMID- 11589047
TI  - [The dopamine system stress reaction in adults of Drosophila virilis is
      controlled by genes of Chromosome 6].
AB  - A linkage group of the gene responsible for changes of DA titer under stress in
      adults of D. virilis was determined. Line 160 of D. virilis, all autosomes of
      which bear visible recessive mutations, was used as an analyzer. Flies of lines
      160 and 147 were shown to differ in DA content under normal conditions and in the
      way DA metabolic system reacts to stress. Among the offspring of the analyzing
      cross, groups of flies were found with one testable autosome from line 147 and
      all other chromosomes from line 160. Results of the DA titer measurements in
      flies of these groups under stress conditions have proved that the gene in
      question is linked to chromosome 6.

PMID- 11589048
TI  - [Influence of selection forms on genetic structure of domestic animals].
AB  - Analysis of genetic structure of pure and crossbred sheep and cattle with the use
      of genetic-biochemical markers was carried out. Data on breed- and locus-specific
      genetic traits, stable in the time, were obtained. In sheep, breed-specific
      peculiarities of genetic structure partly related with the belonging of breeds to
      breed groups with fine-, semi-fine and coarse wool. The preferable influence of
      artificial selection at the phenotype complex traits in comparison with natural
      selection and animal origin on the genetic structure of crossbred sheep was
      revealed. However, the more profound effects of natural selection on the genetic
      structure of crossbred cattle were observed.

PMID- 11589049
TI  - [Genetic study of psoriasis in the Kharkov population].
AB  - By means of genetic analysis of 400 individuals suffering from psoriasis the
      mendelian inheritance model have been rejected: the segregation frequencies are
      SFNxN = 0.083 and SFNxA = 0.1474. The heritability of psoriasis in the polygenic
      model is about 100%. The main gene model with incomplete penetration have been
      proposed (p = 0.044, [symbol: see text]1 = 6.1%, [symbol: see text]2 = 82.2%).
      0.189% residents of Kharkov population are homozygotes and 8.32% heterozygotes on
      psoriatic gene, 0.155% residents are suffering from psoriasis heterozygotes and
      0.508% heterozygotes. Among individuals suffering from psoriasis 23% are
      homozygotes and 77% heterozygotes.

PMID- 11589050
TI  - [Species specificity of karyotype instability under conditions of radionuclide
      contamination (the Chernobyl Nuclear Power Plant) in the voles, Micrototus
      oeconomus, Micrototus arvalis, and Clethrionomys glareolus].
AB  - The comparative analysis of frequencies of different type cytogenetic anomalies
      in voles Microtus oeconomus, Microtus arvalis, Clethrionomys glareolus trapped in
      territories with different levels of radionuclide contamination inside the 30-km
      zone of estrangement around the Chernobyl NPP was carried out. Animals with
      constitutive chromosome abnormalities were not revealed. The frequency of
      lympocytes with micronuclei was the most universal and sensitive character to
      chronic low-dose radiation in investigated species. The species-specific relation
      was observed between level of radionuclide contamination in trapping zone and
      increase in frequencies of cytogenetic abnormalities: aneuploidy in Microtus
      arvalis and metaphase plates with asynchronous centromere fission in Microtus
      oeconomus. Common vole appears to be the most sensitive species of investigated
      ones to chronic low-dose ionizing irradiation.

PMID- 11589051
TI  - [Genetic structure of local Ukrainian cattle breeds].
AB  - Analysis of 6 cattle breeds (5 local Ukrainian breeds and the Holstain breed) on
      the 9 polymorphous molecular-genetic markers (transferrin, ceruloplasmin, amylase
      1, posttransferrin, receptor to vitamin D, haemoglobin, leptin, kapa-casein) was
      carried out. The rare allele of transferrin was revealed in two local breeds and
      the rare allele of leptin--in two another local breeds. Associations between
      syntenic loci (transferrin, ceruloplasmin, kappa-casein, receptor to vitamin D)
      were observed only in the local breeds but not in the Holstain one. Locus
      specific conservation of the ancestor allelic variants in the local breeds and
      effect of selection on interloci associations are discussed.

PMID- 11589052
TI  - [Clinical genealogy and genetic-mathematical study of families of probands with
      uterine cancer in the Chernovitsy Region].
AB  - Complex clinic-genealogical and genetic-mathematical investigation of 482
      patients with uterus cancer from Chernovtsy region was carried out. It was proved
      that primary in the population is multifactoral origin of uterus cancer.
      Percentage of genetic component in general susceptibility to disease was 11.40
      9.40. Recurrent risk of the malignant tumor in progeny has been estimated.
      Results of the investigation are the base for development and execution of uterus
      cancer precaution and segregated with it oncopathology in proband relatives.

PMID- 11589054
TI  - [Comparative analysis of genetic variation in two groups of Crimean pine trees
      with different levels of tolerance to industrial pollutants in the environs of
      the city of Mariupol].
AB  - The comparative analysis of genetic variability of two groups of young Pinus
      pallasiana D. Don. trees with different degree of tolerance to industrial
      pollution, defined in plantations of Mariupol and its environs, has been
      performed on the basis of polymorphism investigations in 20 isoenzyme loci
      controlling 9 enzyme systems. In these groups of plants with high and low
      quantity of needles on the growing sprouts differences in the levels of genetic
      variability, as to average criteria, have not been found.

PMID- 11589053
TI  - [Cytogenetic effects of toxic metal salts on apical meristem cells of Allium cepa
      L. seed roots].
AB  - Comparative analysis of the influence of the salts of Cd, Pb, Ni, Al, Cu and Zn
      at concentrations 10(-6)-10(-3) M on cytogenetic parameters of Allium cepa apical
      meristem cells was carried out. It was shown that these metal compounds could
      induce both the clastogenic and the aneugenic effects (including mitosis and
      cytokinesis disturbances). Based on ability to cause the chromosome aberrations
      the metal salts were arranged in such row of genotoxicity: ZnSO4 > Pb(CH3COO)2 >
      Al(NO3)3 approximately NiSO4 > CdCl2 > CuSO4. The investigated compounds of
      cadmium, lead, nickel and aluminum were found to be more effective aneugens than
      clastogens. According to our data NiSO4 had the strongest antimitotic activity
      (it increased the percentage of chromosome lagging of, multipolar anaphases, C
      mitoses in 69.6 times, compared to the control). The ability of other metal salts
      to induce such abnormalities decreased in the range: CdCl2 > Al(NO3)3 >
      Pb(CH3COO)2 > CuSO4 > ZnSO4. Increasing of binuclear cells on the slides was
      revealed after treatment by all tested substances, however Ni sulfate was found
      as the strongest inducer of cytokinesis abnormalities. Presented results allowed
      to suggest that cytoskeleton could be a cell target for salts of some metals
      (especially for NiSO4).

PMID- 11589055
TI  - [Variation of ultrastructural organization of the mitochondria of pea cells in
      vitro].
AB  - Unusual huge organelles together with mitochondria of typical organization were
      found in a part of population of callus cells of pea. They like mitochondria are
      surrounded by two biologic membranes, the inner one has invaginations. Inclusions
      in the matrix are a specific character of structural organization of these
      unusual mitochondria. These inclusions look as electronically dense bars that
      extend parallel to longitudinal axis of organelle and consist of fibril-like
      elements. Organization of inclusions and cristae as well as a shape of organelles
      are changing during cell development. Possible nature of the unusual mitochondria
      is discussed.

PMID- 11589056
TI  - [Determination of "hybrids" in simple hybrids of maize by SSR-PCR].
AB  - The results of SSRP-analysis of molecular-genetic polymorphism in maize inbred
      lines and simple hybrids are presented. Character of inheritance of amplicons
      obtained by SSR-PCR-method was investigated. Test-system for determination of
      hybridity of simple maize hybrids was proposed, which showed high probability of
      exclusion of unrelative male forms.

PMID- 11589057
TI  - [Application of RAPD for making DNA markers to Vrn genes].
AB  - The possibility of using the PCR with arbitrary primers to mark Vrn genes, Vrn3
      in particular, was investigated. RAPD-analysis of DNA of near isogenic lines on
      Vrn1, Vrn2 and Vrn3 loci in genefone of four varieties of winter wheat were
      carried out. Monogenic dominant lines by Vrn3 locus possessed 657 b.p.
      polymorphic DNA fragment. The possibility of using this polymorphic DNA amplicon
      as a molecular marker was confirmed by results of RAPD-analysis of DNA of some
      commercial wheat varieties of different ecological-geographic origin possessing
      dominant Vrn3 alleles, as well as by RAPD-analysis of F2 population from cross of
      monogenic Vrn3 dominant spring line with its recurrent parent--winter wheat
      variety Mironovskaya 808. The results of RAPD are comparable with hybridological
      analysis data concerning type of development of plants from F2 population.

PMID- 11589059
TI  - [Transgene transfer and inheritance under genetic transformation in maize].
AB  - Achievements are discussed regarding in genetic transformation of maize is
      examined from that point of view what cells, tissues and organs can be the
      targets for the alien gene transfer. The review of available data on genotypical
      peculiarities of transgenesis and inheritance of alien genes included in the
      maize genome are presented.

PMID- 11589058
TI  - [Irradiation as a test-factor revealing dark DNA repair capacity of seeds].
AB  - Dark repair of DNA was studied in embryos excised from the advanced sugar beet
      seeds. Significant increase (from 19 to 321%) in the level of dark DNA repair has
      been established for all studied conditions of the advanced treatment. Acute 
      irradiation has been used to investigate the ability of advanced seeds to repair
      additional DNA damages caused by a standard irradiation dose. It has been
      concluded that irradiation factor allows to test capacity of DNA repair systems.
      The later, we suggest, can be used to define the optimal conditions for the seed
      advancement.

PMID- 11589060
TI  - [Use of genomic in situ hybridization for the genetic study of common wheat
      Triticum aestivum L. and its close relatives].
AB  - The literature data on use of genomic in situ hybridization (GISH) for genetic
      studying of common wheat and its close relatives are reviewed. The conclusions as
      to the necessity of complex investigation of genetic material using GISH and
      other modern methods are drawn.

PMID- 11589061
TI  - Chemotherapeutic prophylaxis of superficial bladder tumors.

PMID- 11589062
TI  - Prostate cancer in the older man.
AB  - Most men diagnosed with prostate cancer are more than 65 years of age. Therefore,
      a discussion of the issues surrounding the diagnosis, prevention, and treatment
      of prostate cancer in older men is, in many ways, a review of prostate cancer in
      general. Nonetheless, older patients with prostate cancer are often faced with a
      different set of problems than younger patients. For instance, if preventive
      strategies prove useful, they will have important implications for older men.
      Even a significant delay in diagnosis could greatly benefit the elderly
      population. Prostate-specific antigen (PSA) screening is controversial for men of
      any age but, for older men, screening may impart a risk to quality of life that
      may outweigh the potential advantages of diagnosis and treatment. Results of a
      large follow-up study of patients treated with radical prostatectomy suggest that
      even men with rising PSA values after surgery can have a relatively benign and
      protracted course. The survival rates noted in this study, however, were only for
      a select population of surgical patients, and, in fact, higher prostate cancer
      death rates have been observed for patients adopting the watchful waiting
      approach. Older men who request some form of primary therapy are increasingly
      being treated with brachytherapy, despite the lack of randomized trials
      demonstrating efficacy compared to external-beam radiation therapy, surgery, or
      watchful waiting. Contrary to an often-held view, older prostate cancer patients
      may have more morbidity from long-term testosterone suppression than younger
      patients. On the other hand, chemotherapy seems to be as well tolerated overall
      in older patients as in younger patients.

PMID- 11589063
TI  - Considerations in the diagnosis and management of brain metastases.
AB  - Brain metastases are a common complication of systemic cancer and a significant
      cause of morbidity. For patients whose brain metastases remain untreated, the
      prognosis is poor. The advent of contrast-enhanced magnetic resonance imaging has
      made accurate diagnosis of brain metastases among symptomatic patients a much
      more manageable task. However, approximately one-third of patients with
      intracranial metastases are asymptomatic, and therefore, greater awareness of the
      risk factors for developing brain metastases may permit better targeting of "at
      risk" patients for further evaluation. Advances in technology and surgical
      techniques have created more options for the management of brain metastases via
      the use of various combinations of surgery, irradiation, and stereotactic
      radiosurgery. However, successful application of these therapies has redefined
      the potential for long-term morbidity associated with radiation therapy. Thus,
      considerable effort is now being directed toward finding a balance between the
      use of whole-brain radiotherapy, surgery, and radiosurgery, and tailoring those
      treatment modalities to the unique needs of the patient. Although more
      prospective, randomized studies are needed before an informed consensus regarding
      the optimal means for managing brain metastases can be established, this article
      provides an overview of some of the advantages and disadvantages of therapeutic
      approaches recently under study.

PMID- 11589064
TI  - Clinical trials referral resource. Current clinical trials of epothilone B analog
      (BMS-247550).

PMID- 11589065
TI  - Selective estrogen-receptor modulators in 2001.
AB  - Tamoxifen (Nolvadex), a selective estrogen-receptor modulator, or SERM, is
      currently the endocrine therapy of choice for all stages of hormone-responsive
      breast cancer. Only tamoxifen has been approved by the US Food and Drug
      Administration to reduce the incidence of breast cancer in high-risk women.
      Despite tamoxifen's antiestrogenic effects in breast tissue, it exhibits
      paradoxical estrogenic effects in other tissues in the body. These effects result
      in the maintenance of bone mineral density, but a three- to fourfold increase in
      endometrial cancer in postmenopausal women. Additionally, tamoxifen can result in
      troublesome hot flashes and serious thromboembolic events. For this reason,
      current research is focusing on new agents that may maintain the beneficial
      effects of tamoxifen while reducing its adverse effects. Raloxifene (Evista) is
      another SERM, approved for the prevention of osteoporosis in postmenopausal women
      and now being compared with tamoxifen in an ongoing breast cancer prevention
      trial. Like tamoxifen, raloxifene is associated with hot flashes and
      thromboembolic events, but its association with the risk of endometrial cancer is
      unknown. A number of new SERMs are in preclinical or clinical development in an
      attempt to improve upon the safety profile of tamoxifen. Additionally, selective
      aromatase inhibitors are being examined in the early breast cancer setting.

PMID- 11589066
TI  - Gene therapy for ovarian cancer.
AB  - Advances in molecular virology and biotechnology have led to the engineering of
      vectors that can efficiently transfer genes to target cells. Gene therapy
      strategies were developed along two lines: Cytotoxic approaches involve the
      transfer of genes that encode enzymes, which convert inactive prodrugs into
      cytotoxic drugs. Corrective gene therapy approaches aim to repair specific
      molecular alterations in signal transduction mechanisms that control the cell
      cycle or induce apoptosis. Clinical evidence suggests that gene therapies are
      best suited for patients with minimal residual disease. Multimodality approaches
      with conventional strategies and novel therapeutic tools in various combinations
      will most likely prove advantageous, compared to single-modality treatments.
      However, clinical trials will need to test these hypotheses.

PMID- 11589067
TI  - Clinician safety: assessing and managing the violent patient.
AB  - Many clinicians deny the possibility of violence occurring in their practices,
      and this denial has its roots in fear of violence or overconfidence in safety. To
      appropriately address the issue of violence, clinicians must engage in proactive
      behaviors and attitudes that will ensure their safety.

PMID- 11589068
TI  - Program components of a comprehensive integrated care system for seriously
      mentally ill patients with substance disorders.
AB  - Using an integrated theoretical framework, a continuous and comprehensive model
      system of care for dual diagnosis patients can be designed.

PMID- 11589069
TI  - Combining individual and family treatment: guidelines for the therapist.
AB  - Successfully combining individual and family treatment for psychosis-prone
      outpatients who live with their families is a process of keeping the needs of the
      patient and the family in balance. The therapist has to respond to each in an
      evenhanded way that preserves an alliance with both. Through guidelines and case
      reports, this chapter describes how to maintain that balance. The therapist
      patient relationship is the core of treatment and keeps the clinician's focus
      squarely on the individual needs of the patient. In keeping with that focus, the
      therapist encourages self-determination on the patient's part and sets up
      opportunities for the family to communicate directly with the therapist in front
      of the patient, rather than surreptitiously behind the patient's back. In keeping
      with a collateral emphasis on the family, the therapist involves the family
      regularly and early in the course of treatment, respects the family's knowledge
      of the patient, puts that knowledge to use, and works with the family to deal
      promptly and effectively with incipient emergencies. The therapist knows that it
      is not only the therapist but also the family who stimulate a patient to change.
      The therapist, building on whatever strengths the patient and family possess,
      enlists the family as an ally in promoting and bringing about therapeutic
      progress.

PMID- 11589070
TI  - The biological basis of mental illness.
AB  - Belief in the biological roots of mental illness will govern some of what we do
      in a psychiatric rehabilitation program.

PMID- 11589071
TI  - The uninstitutionalized generation: a new breed to psychiatric patient.
AB  - Our first generation of young adult chronic psychiatric patients since
      deinstitutionalization has emerged in the community. Updated research results and
      case studies show different patterns of emergence but similar indications for
      clinician response.

PMID- 11589072
TI  - From mental health professional to expert witness: testifying in court.
AB  - Our democratic principles rest on the belief that truth is discovered through the
      fair and open combat of ideas in a court of law. When mental health professionals
      participate in this adversary process as expert witnesses, it is essential for
      them to understand that attorneys will attempt to impeach their credibility.
      Mental health professionals who appreciate the spirit and mechanics of courtroom
      communication will be best prepared to protect the integrity of their testimony.
      The courtroom communications model provides experts with a conceptual framework
      utilizing three components: the speaker is the expert, the message is testimony,
      and the audience is the judge or jury. Within the structure of this model,
      communication principles from social psychology can be used to enhance the
      clarity of testimony and to prevent attorneys from distorting the expert's
      opinions. First and foremost, expert witness testimony must be formulated on
      accepted scholarly and ethical standards. To establish credibility, experts must
      appear knowledgeable and trustworthy to the judge and jury. The expert must come
      to court prepared for both direct examination and cross-examination, know when to
      emphasize logic or emotion, tailor speech in order to reach the maximum number of
      jurors, and remain nondefensive by projecting the same demeanor regardless of
      which side is conducting the examination. The role of the expert witness is
      forever changing because the judicial system--like the mental health field-
      continues to evolve. Although the adversary process has undergone dramatic
      changes over the past eight hundred years, historical vestiges continue to echo
      throughout our courtrooms. Today expert witnesses are the champions of both
      victims and the accused. Legal disputes are increasingly being decided by the
      battle of the experts, who must undergo the ordeal of cross-examination. When you
      consider the brutality of ancient ordeals, responding to attorneys armed with
      questions may not seem so daunting.

PMID- 11589073
TI  - The cultural context of interventions for family members with a seriously
      mentally ill relative.
AB  - This chapter provides an overview of interventions for relatives of severely
      mentally ill individuals. The author discusses the design and use of these
      interventions in the context of the cultural characteristics of families and
      providers, as well as the culture of the interventions themselves.

PMID- 11589074
TI  - The place of spirituality and religion in mental health services.
AB  - Mental health professionals have raised concerns about the role of spirituality
      and religion in services for people with severe mental disorders, but this
      chapter offers compelling reasons for increased attention to spiritual issues in
      service delivery.

PMID- 11589075
TI  - The state of the state mental hospital at the turn of the century.
AB  - There is a core of services whose specific content varies from place to place
      that still appears to belong to the state mental hospital.

PMID- 11589076
TI  - [Behcet's disease].

PMID- 11589077
TI  - [Behcet's disease: retrospective study].
AB  - BACKGROUND: Since the criteria for the diagnosis of Behcet's disease was
      established several isolated cases have been reported to the literature with
      clinical manifestations associated. We tried to analyze the clinical parameters
      associated to this disease in 24 patients in our hospital. METHODS: A
      retrospective analysis was made of the patients diagnosed of Behcet's disease at
      Hospital General of Valencia since 1990 to 2000. The diagnosis of Behcet's
      disease was made by the criteria of the International Study Group for Behcet
      disease. Data regarding personal, clinical manifestations and clinical course
      were collected. RESULTS: Of the 24 cases, fourteen (58%) were men and ten (42%)
      were women. The median of the diagnosed was 33 years. All of them had oral
      recidivant ulcers. The genital ulcers appeared in twenty (83%) cases. Thirteen
      cases (54%) had ocular manifestations, and the skin lesions appear in 10 cases
      (42%). We review other clinical manifestations associated to Behcet disease:
      articular clinical appear in 17 cases (70%), digestive manifestations in six
      cases (25%), neurological manifestations three cases (12%), vascular clinical two
      cases (8%). CONCLUSIONS: Our results are similar to the Mediterranean expression
      of Behcet's disease. We must study the clinical manifestations associated to this
      disease that are not include in the criteria of diagnosis.

PMID- 11589078
TI  - [Diabetic ketoacidosis in an emergency department].
AB  - OBJECTIVE: We study clinical data and differences in the patients with Diabetic
      Ketoacidosis (CAD) attended in an Emergency Department (ED). METHODS: We
      described 15 patients with criteria for diagnosis of CAD during a 12-month
      period. We value prospectively clinical data, precipitating factors, diagnosis
      associated, previous diagnosed diabetes, complications, mortality and use of and
      intensive care unit (UCI). We comparing groups according two characteristics: age
      group and prior diagnosis of diabetes mellitus.

PMID- 11589079
TI  - [Prognostic factors of bacteremia: prospective study].
AB  - BACKGROUND: To identify the epidemiology and risk factors with influence in the
      outcome and mortality of a series of bacteriemic patients. MATERIAL AND METHODS:
      A prospective study of bloodstream infections with clinical significance detected
      in a secondary hospital of 650 beds over period from May 1998 to May 1999. The
      true bacteriemia was defined in basis to the criteria both the physician and
      microbiologist. A total of 16 variables were defined and categorized such as
      clinical-epidemiologic, intrinsic risk factor, extrinsic risk factor, outcome and
      survival. We used SPSS statistical package: For cuantitative variables we carried
      out with the mean with confidence interval of 95%, for cualitative variables:
      number and %. Univariate analysis of the results was carried out with the X2 test
      and t Student, the survival was expressed with Kaplan Meyer graphics and the
      logistic regression model. RESULTS: A total of 320 positive blood cultures were
      studied but only 272 blood cultures were considered true bacteriemia in 259
      patients. The calculated incidence of significant episodes of bacteriemia per
      1000 admissions/year was 13. The overall mortality was 22% whereas death
      attributable to bacteriemia was 16%. The mean age was 66.9 years (IC 95% 65-69),
      59% episodes occurred in men. The 78% episodes occurred in patients hospitalized
      in medical services. 52% episodes were of nosocomial infection and 48% of
      community acquired infection. According to the severity of the underlying
      disease, 15% had fatal diseases and 35% episodes occurred in patients without
      underlying disease. According to the univariant analysis, the variables which
      where significantly associated with greater risk death were: etiology (fungus),
      septic shock, the inadequate antibiotic therapy, presence of extrinsic factors
      (central intravenous catheter, performance of invasive procedures, previous
      antimicrobial therapy) and the hospital stay of less than 10 days. According to
      the multivariable analysis showed that the factors remaining independent
      predictors of mortality were: septic shock (p < 0.0001, OR: 8), inadequate
      antimicrobial therapy (p < 0.005, OR: 6.7), existence of two or more extrinsic
      risk factors (p < 0.04). CONCLUSIONS: The presence of septic shock was the most
      important variable which influenced in the mortality in our serie, together with
      inappropriate antimicrobian therapy and the association of various extrinsic risk
      factors. These variables could be modified partly, for this reason the aggressive
      hemodynamic control and the early and appropriate antibiotic therapy would be the
      support of the successful bacteriemia management.

PMID- 11589080
TI  - [Cost effectiveness of the use of spironolactone in the treatment of chronic
      heart failure].
AB  - BACKGROUND: Chronic heart failure (CHF) is the first cause of hospitalization in
      elderly patients. The use of spironolactone in patients with CHF (degree III-IV)
      reduces their mortality and the rate of hospitalization. The aim of this study
      has been to assess the efficiency of using spironolactone in the treatment of CHF
      when compared with the use of conventional treatment alone. MATERIAL AND METHODS:
      The study has been performed through the design of a decision analytic model. A
      cost-effectiveness analysis was carried out by doing a simulation of 2 hypothetic
      cohorts of 1000 patients with CHF. It was evaluated the costs of each extra life
      year gained with each alternative under study. Data included have been obtained
      from Rales and the mean survival time for these patients has been considered of
      4.3 years. Only direct medical costs have been included into this analysis. The
      chosen perspective has been the society and the time horizon included has been of
      4.3 years. RESULTS: The cost/effectiveness ratio has been better in the
      spironolactone group (1,961,214) than in the standard treatment alone (2,242,912)
      and each extra life year gained when adding spironolactone to the conventional
      treatment yielded an additional cost of 591,457 ptas. The sensitivity analysis
      performed has shown that the option of using spironolactone presents always a
      better cost/effectiveness ratio even in the worst scenarios. CONCLUSIONS: The
      association of 25 mg/day of spironolactone to the conventional treatment of CHF
      is going to get more life years gained for these patients with a reasonable cost
      and clearly affordable by our National Health Service.

PMID- 11589081
TI  - [Cowden syndrome: clinical case presentation with oral lesions].
AB  - Cowden syndrome is an autosomal-dominant inheritance disease, characterized by
      the presence of skin and oral mucosa multiple hamartomas and nodules, together
      with thyroid and breast anomalies and polyposis of the gastrointestinal tract,
      which tend to undergo malignant transformation, especially in breast and
      thyroids. Therefore, the oral lesions early diagnosis facilitates the
      identification of asintomatic lesions, in other parts of the body. This is the
      case in the report we are to present, in which the patient, probably with the
      Cowden Syndrome, because of the presence of multiple hamartomas in the oral
      mucose diagnosed a breast carcinoma, and other alterations such as thyroid
      calcifications and polyposis of the gastrointestinal tract.

PMID- 11589082
TI  - [Kikuchi-Fujimoto's disease and the association with systemic lupus
      erythematosus].
AB  - Kikuchi-Fujimoto's disease (KFD), Histiocytic Necrotizing lymphadenitis, is a
      rare self-limiting condition characterized by lymphadenopathy, fever and
      neutropenia. The aetiology of KFD is controversial, and its diagnosis is
      confirmed histologically. Although KFD has rarely been reported associated to
      Systemic lupus erythemotosus (SLE) should be ruled out given its different
      prognosis and management. We present the clinical, histological and evolution the
      two cases of patients with Kikuchi's disease; one case had evolution classic and
      the other case were associated with SLE.

PMID- 11589083
TI  - [Leydig cell tumor, gynecomastia, and inferior vena cava thrombosis].
AB  - Leydig cell tumor is a testicular tumor with a low incidence characterized by a
      high estrogens secretion from the tumoral cells. Its more frequent clinical
      presentation is a testicular nodule with or without other endocrine
      manifestations due to estrogenic hypersecretion. We're reporting a case of a
      Leydig cell tumor with high plasmatic levels of estradiol, gynecomastia and
      inferior cava vein thrombosis, which hasn't been described among its clinical
      features up to now. Vascular thrombotic phenomenons have already been reported in
      other clinical situations with hiperestrogesism and they could also be associated
      with these tumors. Patients with Leydig cell tumors could be at a higher risk of
      developing thromboembolic phenomenons because of tumoral hyperestrogenism and
      could present thrombotic complications among the clinical findings.

PMID- 11589085
TI  - [Lung cancer and paraneoplastic syndromes].
AB  - Paraneoplastic syndromes (PNS) are a relatively common manifestation of cancer,
      and in some cases they may be the first symptom. Lung cancer has the highest
      incidence of paraneoplastic syndrome. This fact is important considering a non
      explained endocrinological and neurological syndrome, it may facilitate a prompt
      diagnosis, and in some cases an adequate treatment. PNS evolution seems to be
      parallel to the subjacent cancer. PNS management requires specific measures,
      because in some cases, it may compromise the patient life. Neurological and
      endocrinological PNS associated to lung cancer are revised, and diagnosis and
      treatment of them are updated.

PMID- 11589084
TI  - [Paroxysmal nocturnal hemoglobinuria: pathogenic and therapeutic news].
AB  - Paroxysmal Nocturnal Haemoglobinuria (PNH) is a clinical manifestation of an
      haemathology cell disease, whose etiology has been unknown for many years. We try
      to resume the most relevant facts of this entity and to define the pathogenesis
      which is responsible of the clinical manifestations of the disease.

PMID- 11589086
TI  - [Lymphoedema associated with Lyme disease].

PMID- 11589087
TI  - [Burns in the oral mucosa and skin erosions].

PMID- 11589088
TI  - [Flavimonas oryzihabitans bacteremia in a non-neutropenic patient with cardiac
      disease].

PMID- 11589089
TI  - [Impact of alarm caused by ozone ambient air pollution in a hospital emergency
      service].

PMID- 11589090
TI  - [Acute abdomen as presentation of eosinophilic gastroenteritis].

PMID- 11589091
TI  - [Cardiac tamponade as initial manifestation of systemic lupus erythematosus].

PMID- 11589093
TI  - The past, present, and future perfect profession.

PMID- 11589092
TI  - [Effectiveness of the abdominal CT in diagnosis of the viscero-abdominal fat
      accumulation in HIV patients treated with protease inhibitors].

PMID- 11589094
TI  - TOMAC: an orthognathic treatment planning system. Part 3. VTO construction in the
      vertical dimension.

PMID- 11589096
TI  - The banded Herbst appliance.

PMID- 11589095
TI  - Surgical-orthodontic treatment of an impacted canine with a dentigerous cyst.

PMID- 11589097
TI  - A corrected cephalometric tracing technique for diagnosis of anterior crossbite
      with functional shift.

PMID- 11589098
TI  - A modified archwire tucker.

PMID- 11589099
TI  - [Effect of M3-choline receptor blockade on the ability of muscarinic antagonists
      to prevent catalepsy induced by haloperidol in rats].
AB  - A relationship between the indices of efficacy of the muscarinic antagonists in
      preventing the haloperidol catalepsy and their activity in the tests
      characterizing the interaction of these ligands with various subtypes of m
      cholinoreceptors was studied in rats. A mathematical model was formulated that
      confirmed the previous conclusion concerning the role of of the m1- and m2
      cholinoreceptor blockade in the antiparkinsonian activity of muscarinic
      antagonists. It was established that blocking of the m3-cholinoreceptors
      decreases the anticataleptic activity of m-cholinoblockers with respect to
      haloperidol. It is suggested that the high antihaloperidol activity of pentiphine
      (an acetyleneamine alcohol) is explained by its dopaminomimetic properties rather
      than by the anticholinergic activity.

PMID- 11589100
TI  - [Operator activity and changes in the functional state of central adrenergic
      systems (a neurophysiological study)].
AB  - With a view to increasing the quality of prognosis of the effect of central
      adrenergic drugs upon the operator psychophysiological state and performance, we
      studied correlations between changes in the psychophysiological performance
      parameters and the spectral-coherent EEG characteristics in a group of 20 healthy
      volunteers after moderate enhancement or reduction of the central adrenergic
      system activity by yohimbine and pyrroxan. The two drugs produced a marked
      opposite influence (positive for yohimbine and negative for pyrroxan) upon the
      visual memory, attention, and visual signal analysis, which was correlated with
      opposing changes in the EEG characteristics, predominantly in the right
      hemisphere. This result must be taken into account in determining indications and
      co-unterindications for the particular drug administration to working operators.

PMID- 11589101
TI  - [Specificity of the anti-arrhythmic effect of kappa1-opioid receptor agonists].
AB  - It is demonstrated that intravenous administration of the kappa 1-opioid receptor
      (OR) agonists (-)-trans-(1S,S)-U-50,488 and (+)-trans-(1R,2R)-U-50,488 increases
      heart tolerance to the arrhythmogenic effect of epinephrine in rats. This
      antiarrhythmic effect was completely abolished by preliminary kappa-OR blocking
      with norbinaltorphimine. Preliminary administration of of a high-affinity kappa 1
      OR agonist (-)-trans-(1S,S)-U-50,488 significantly reduced the incidence of
      ventricular arrhythmias upon coronary artery occlusion and reperfusion in vivo.
      The low-affinity (+)-trans-(1R,2R)-U-50,488 does not show antiarrhythmic activity
      under ischemia and reperfusion of myocardium. It is concluded that the
      antiarrhythmic action of kappa 1-OR agonists in the adrenal, ischemic, and
      reperfusion arrhythmia models has a receptor-specific character.

PMID- 11589102
TI  - [Effect of lithium hydroxybutyrate on the circadian dynamics of the urinary
      excretion of Li(+), Na(+), K(+), and Ca(2+) in rats depending on the circadian
      phase of the drug administration].
AB  - In winter solstice, the urinary excretion of Li+ and Na+ in intact rats has a
      uniform circadian profile, while K+ and Ca2+ exhibit a 23-h and 24-h rhythm,
      respectively. The administration of lithium hydroxybutyrate (10 mg/kg, 6 days) at
      8 a.m. forms the 24-h Li+ and Na+ excretion rhythm, while not significantly
      affecting the circadian profiles of K+ and Ca2+. The lithium loading at 8 p.m.
      made the circadian urinary excretion profiles of Ca2+ and Na+ uniform, while the
      excretion of Li+ and K+ acquired a 24-h rhythm. Irrespective of the circadian
      phase, the administration of lithium hydroxybutyrate decreased the average daily
      concentration of Na+ in the urine, while the average concentration of Ca2+
      remains unchanged; the concentration of K+ decreases after lithium
      hydroxybutyrate injections in the morning. Upon the morning treatment, lithium
      cations are excreted faster than after the evening injections.

PMID- 11589103
TI  - [Temperature-dependent contractions of the guinea pig vas deferens mediated by
      P2X receptors].
AB  - The P2X receptor agonist alpha,beta-methylene ATP and purinergic electrical
      stimulation induce contractility response in guinea pig vas deferens. The low
      temperature response observed at 30 degrees C was markedly greater than that at
      37 degrees C and 42 degrees C. The P2X receptor antagonist pyridoxal-6-phosphate
      2',4'-disulfonic acid stronger inhibits the electric-field-induced contractility
      at 30 degrees C than at 37 or 42 degrees C, while no such difference was observed
      for the inhibition of contractility induced by alpha,beta-methylene ATP.

PMID- 11589104
TI  - [Effect of novel anxiolytic agent aphobazole on coherence of the brain
      biopotentials in MR and MNRA rats].
AB  - Effect of the anxiolytic drugs afobazole, diazepam, and chlordiazepoxide on the
      cortical biopotential coherency was studied in MR and MNRA rats with increased
      and decreased level of emotionality, respectively. Afobazole increased a
      difference in the biopotential coherency between rats of the two lines in the
      range of EEG theta, alpha, and beta rhythms. In the subrange of dominating theta
      activity (6.00-7.25 Hz), this effect took place at the expense of reduced
      coherency in MNRA rats in the absence of changes in the MR line. Afobazole
      decreased the biopotential coherency in the alpha activity band (7.5-8.25 Hz) in
      the rats of both lines. This is indicative of the presence of a CNS-stimulating
      component in the pharmacological activity spectrum of afobazole. The expediency
      of using afobazole in patients with different levels of anxiety is discussed.

PMID- 11589105
TI  - [Effect of human recombinant granulocyte colony-stimulating factor on mouse
      hematopoietic and lymphoid organs].
AB  - Experiments on intact CBA/CALac mice demonstrated that single (1.25 mg/kg) and
      repeated (0.125 and 1.25 mg/kg, 30 days) injections of recombinant human
      granulocyte colony stimulation factor lead to reversible dose-dependent
      granulocyte lineage hyperplasia in bone marrow, regenerative neutrophilic
      leukocytosis, and thrombocytosis in peripheric blood and to splenic granulo-,
      erythro-, and thrombocytopoiesis more expressed in males.

PMID- 11589106
TI  - [Use of mirtilene forte and adrusen zinco for correction of oxidative lesions in
      mitochondria in rats OXYS with inherited hyperproduction of free radicals].
AB  - A long-term uptake of a diet supplemented with Mirtilene Forte (Vaccinum
      myrtillus extract) or Adrusen Zinco (a vitamin E complex with zinc, copper,
      selenium and omega-3 polyunsturated fatty acid) improved the functional state of
      liver mitochondria in OXYS rat strain. Adrusen Zinco sharply decreases the level
      of protein and lipid oxidation products. Possible mechanisms of the drug action
      are considered in relationship with their antioxidant properties.

PMID- 11589107
TI  - [Effect of essentiale and riboxin on immunosuppressive properties of thrombocytes
      and erythrocytes during liver intoxication].
AB  - An important factor of immunosuppression development in the case of a toxic liver
      damage caused by D-galactosamine it the interaction of thrombocytes and light
      erythrocytes with serum factors. The introduction of essentiale and riboxin
      favors this interaction and stimulates the development of immunosuppression in
      thrombocytes.

PMID- 11589108
TI  - [Effect of hypoxic stress on xenobiotic metabolism and activities of various
      isoforms of cytochrome P-450].
AB  - It was shown that animals divided into groups with respect to the initial
      sensitivity (low and high resistance) to hypoxia (lack of oxygen in air) differ
      by their liver monooxygenase enzyme complex reaction to the model acute hypoxia.
      Low-resistant rats exhibited an increase in cytochromes P-450 and b5, in the rate
      of oxidative metabolism of amidopyrine, aniline, and ethoxyresorufine, and in the
      rate of antipyrine elimination (manifested by a decrease in the elimination half
      time and by an increase in the elimination constant), which is evidence of the
      increasing activity of cytochromes P-450, 1A1, 1A2, 2C8, and 3A1. In response to
      acute hypoxia, highly hypoxia-resistant animals exhibited an increase in the
      rates of diazepam and methoxyresorufine metabolism, which reflected a higher
      catalytic activity of P-450, 2C6, 2B1, and 1A2 isoforms. At the same time, the
      rate of antipyrine elimination decreases (the elimination half-time increases,
      while the clearance and the elimination constant decrease).

PMID- 11589109
TI  - [Immunopoiesis- and erythropoiesis-modulating properties of trecresan in
      experimental immune deficiency].
AB  - The effect of trecrezan, a new immunoactive biostimulator, was studied in
      (C57BL/6 x DBA/2)F1 mice with immunodeficiency and anemia syndromes induced by a
      chronic guest-versus-host reaction. The drug combines immuno- and erythromodulant
      properties, being capable of eliminating anemia, decreasing the number of
      erythrokaryocytes and BFUs in bonemarrow of ill mice, and normalizing primary
      humoral immune response. Possible mechanisms of trecrezan action are discussed.

PMID- 11589110
TI  - [Anti-inflammatory activity of domestic papain].
AB  - The influence of domestic papain to the course of experimental inflammation due
      to formalin, dextrane, histamine, serotonin and infectious arthritis has been
      studied. The domestic papain in doses of 0.325 and 0.75 mg/kg possesses strongly
      marked antiinflammatory activity and this ability is no less than that of
      butadion and indomethacin.

PMID- 11589111
TI  - [Experimental study of anti-inflammatory and wound healing properties of 1%
      ointments of 18-dehydroglycyrrhetic acid sodium salt].
AB  - Experiments on animals showed that 1% ointments of 18-dehydroglycyrrhetic acid
      sodium salt studied possess pronounced antiinflammatory and wound-healing
      properties.

PMID- 11589112
TI  - [Effect of Silybum marianum oil and legalon on lipid peroxidation and liver
      antioxidant systems in rats intoxicated with carbon tetrachloride].
AB  - An oil obtained from the seeds of Saint-Mary thistle (Silybum marianum) and the
      drug legalon (silybinin) prepared from this plant produce an antioxidant effect
      on liver tissues of rats poisoned with carbon tetrachloride. Legalon (25 mg/kg)
      and the oil (2000 mg) reduced the level of lipid peroxidation, increased the
      catalase activity, but did not reduce the concentration of selenium in liver
      (which decreased as a result of CCl4 intoxication). Legalon significantly
      increased the activity of superoxide dismutase in liver tissues, while the Saint
      Mary thistle oil did not produce such effect.

PMID- 11589113
TI  - [Experimental study of pharmacotherapeutic effect of phytoecdisteroids and
      nerobol in toxic liver damage].
AB  - Phytoecdysteroids ecdysteron and turkesteron isolated from Ajuga turkestanica
      (Rgl.) Brig. decrease the manifestations of uremic intoxication in rats with
      experimental renal pathology induced by a nephrotoxic mixture (containing uranyl
      acetate and glycerol). Injected in a dose of 5 mg/kg, the drugs restore
      glomerular filtration level, favor the disappearance of the albuminuria and
      normalize urinary sediments. The nephroprotector effect of the phytoecdysteroids
      studied resembles the action of a steroidal anabolic drug nerobol.

PMID- 11589114
TI  - [Effect of gamma-linolenic acid on microsomal oxidation in the rat liver
      following gamma-irradiation].
AB  - The antioxidant and radioprotector properties of gamma-linolenic acid isolated
      from the seeds of Borago officialis were studied on rats gamma-irradiated to a
      dose of 1 Gy. The irradiation caused an increase in the content of malonaldehyde
      in microsomal liver fraction and disturbed the metabolism of xenobiotics. The
      administration of gamma-linolenic acid in the form of a commercial drug
      Neoglandin (daily dose, 150 mg/kg, p.o.; over 1, 3, or 7 days after irradiation
      reduced the level of lipid peroxidation (for all treatment schedules), normalized
      the activity of NADPH-oxidase, NADH-oxidase, and NADPH-reductase, and increased
      the content of cytochromes P-450 and b5 as compared to bothirradiated and control
      animals.

PMID- 11589115
TI  - [Minimum-invasive model of the rat brain focal ischemia].
AB  - The problem of brain ischemia damage treatment stimulates the search for new
      effective methods, which are studied on various experimental models. Most of such
      models possess significant disadvantages, producing hypoxia in the whole
      organism, being poorly controlled, involving serious traumas, and still being far
      from true pathological mechanisms accompanying the ischemia development. A model
      of focal brain ischemia in rats, induced by middle cerebral artery intravasal
      occlusion, is free of these disadvantages.

PMID- 11589116
TI  - [Biological evaluation of the effect of beta-lactam antibiotics on apoptosis in
      human lymphoid cells in vitro].
AB  - Models are developed that allow the effect of beta-lactam antibiotics on the
      level of apoptosis in human lymphoid cells to be evaluated in vitro. The
      antibiotics produced a dose-dependent decrease in apoptosis of mature lymphocytes
      both under normal conditions and in the state of dexamethasone-induced
      immunodepression. The beta-lactam antibiotics also affect the apoptosis in a pre
      B-lymphoblast model. The dexamethasone-induced apoptosis is inhibited by beta
      lactam antibiotics only in high doses.

PMID- 11589117
TI  - [Psychotropic effects of alkaloid lappaconitine and its various derivatives].
AB  - The psychotropic activity of (I, base), its N-oxide, and a complex of the base
      with 18-alpha-H-glycyrrhizic acid (1:2) was studied. It was established that I
      and its N-oxide exhibit dopaminopositive effect whereas the complex produces a
      serotoninopositive effect. Toxicities of the lipophilic I is half that of the
      hydrophilic; toxicity of N-oxide and the complex are 60 and 100 times lower than
      the activity of lappaconitine (base).

PMID- 11589118
TI  - [Physiological and pharmacological characteristics of epiphyseal neuropeptides].
AB  - Various epiphyseal neuropeptides, participating in regulation of the secretory
      processes, are capable of inducing systemic changes. This circumstance determines
      both pharmacological and therapeutic properties. The drug elitalamine,
      representing a polypeptide extract, ensures effective treatment of the immune
      system and brain disorders and tumors and allows a prophylaxis of tissue aging.

PMID- 11589119
TI  - To Err is Human: Building a Safer Health System in 1999.

PMID- 11589120
TI  - A new health system and its quality agenda.
AB  - This article reviews recent work on healthcare quality, highlights findings and
      recommendations of the Institute of Medicine (IOM) reports on medical errors and
      quality, and describes response to the reports to date. In it, Detmer, chair of
      the IOM's Board of Health Care Services and a member of its Committee on Quality
      of Health Care in America, identifies implications of the reports for healthcare
      delivery organizations and professionals and outlines ways organizations and
      professionals can improve the six dimensions of patient quality defined by the
      IOM. Sustained efforts at the point of care and in policy development are needed
      to overcome cultural inertia, realign incentives, support innovation, and address
      technical and human resource issues. Success requires that healthcare executives
      embrace the goal of transforming the healthcare sector into a true system and
      provide leadership for their organizations and communities in this most
      fundamental of challenges for twenty-first century healthcare.

PMID- 11589121
TI  - A time for concerted action.

PMID- 11589122
TI  - Key themes of the analysis of the IOM reports.

PMID- 11589123
TI  - Quality improvement should be healthcare's essential business strategy.

PMID- 11589124
TI  - Brain preparations for maternity--adaptive changes in behavioral and
      neuroendocrine systems during pregnancy and lactation. An overview.
AB  - Pregnancy, parturition and lactation comprise a continuum of adaptive changes
      necessary for the development and maintenance of the offspring. The endocrine
      changes that are driven by the conceptus and are essential for the maintenance of
      pregnancy and are involved in the preparations for motherhood are outlined. These
      changes include large increases in the secretion of sex steroid hormones, and the
      secretion of peptide hormones that are unique to pregnancy. The ability of these
      pregnancy hormones to alter several aspects of brain function in pregnancy is
      considered, and the adaptive importance of some of these changes is discussed,
      for example in metabolic and body fluid adjustments, and the induction of
      maternal behavior. The importance of sex steroids in determining the timing of
      the various adaptive changes in preparing for parturition and maternal behavior
      is emphasized, and the concept that the actions of prolactin and oxytocin,
      quintessential mammalian motherhood neuropeptides, can serve to coordinate a
      spectrum of adaptive changes is discussed. The part played by oxytocin neurons
      and their regulatory mechanisms is reviewed to illustrate how neural systems
      involved in maternity are prepared in pregnancy via changes in phenotype,
      synaptic organization and in the relative importance of their different inputs,
      to function optimally when needed. For oxytocin neurons secreting from the
      posterior pituitary, important in parturition and essential in lactation, these
      changes include mechanisms to restrain their premature activation, and
      adaptations to support synchronized burst firing for pulsatile oxytocin secretion
      in response to stimulation via afferents from the birth canal, olfactory system
      or suckled nipples. Within the brain, expression of oxytocin receptors permits
      centrally released oxytocin to facilitate the expression of maternal behavior.
      Changes in other neuroendocrine systems are similarly extensive, leading to
      lactation, suppression of ovulation, reduced stress responses and increased
      appetite; these changes in lactation are driven by the suckling stimulus. The
      possible link between these adaptations and changes in cognition and mood in
      pregnancy and post partum are considered, as well as the dysfunctions that lead
      to common problems of depression and puerperal psychoses.

PMID- 11589125
TI  - Peripartum plasticity within the hypothalamo-pituitary-adrenal axis.
AB  - The hypothalamo-pituitary-adrenal (HPA) axis plays important roles in the
      adaptive changes in physiology that occur during pregnancy and lactation.
      Although the axis still exhibits a pulsatile pattern of secretion, the normal
      diurnal rhythm of pulse amplitude is lost during lactation, such that mean basal
      levels remain constant throughout the day. In addition, the peripartum period is
      associated with a remarkable plasticity in stress-induced HPA activity, in that
      the increase of HPA activity normally seen in response to either physical or
      psychological stresses in the non-reproductive state become severely attenuated
      or absent in the lactating animal. This stabilization of both basal and stress
      induced HPA activity may be important for maintaining a constant endocrine
      environment, thereby preventing any programming effects on the developing
      offspring. Attenuation of the stress response is initiated in late pregnancy and
      is temporally associated with luteolysis, indicating possible steroid hormone
      involvement. Indeed, mimicking the luteolytic changes in oestrogen and
      progesterone levels in non-pregnant animals induces a similar attenuation of the
      stress response. Furthermore down-regulation of the stress response is, at least
      in part, centrally mediated since in the period following luteolysis rats will
      show a decreased level of stress-induced neuronal activation of the PVN, as
      measured by the expression of either c-fos or CRH mRNAs. Persistence of this
      adapted state is dependent upon the continued suckling stimulus, as removal of
      the offspring litter rapidly leads to resumption of HPA responses to and the
      appearance of an exaggerated diurnal rhythm. The underlying mechanisms
      responsible for this stress hyporesponsiveness may include plasticity of
      noradrenergic and oxytocin pathways. In view of its role in other reproductive
      behaviors, a stress-inhibiting effect of oxytocin may reflect a more widespread
      co-ordinating role in the peripartum animal.

PMID- 11589126
TI  - The neurobiology of stress in human pregnancy: implications for prematurity and
      development of the fetal central nervous system.
AB  - Adverse early experience, including prenatal maternal psychosocial stress, has
      the potential to negatively influence developmental processes through both
      physiological and behavioral mechanisms. This in turn may have adverse
      consequences for the mental and physical health, well-being and aging of the
      individual throughout the entire life-span. We have initiated a program of
      research on humans to examine the consequences of maternal stress and related
      factors in pregnancy on the length of gestation, fetal growth, and brain
      development. We have also investigated the physiological mechanisms that are
      involved. In this chapter we outline the theoretical rationale for this work and
      give an overview of our findings to date. These findings support a significant
      and independent role for behavioral processes such as maternal prenatal stress in
      the etiology of prematurity-related outcomes, and suggest that these effects are
      mediated, in part, by the maternal-placental-fetal neuroendocrine axis;
      specifically by placental corticotropin-releasing hormone. Using a fetal
      challenge paradigm as a novel method for quantifying fetal neurologic maturity in
      utero, we have found that the maternal environment exerts a significant influence
      on the fetal autonomic nervous system and on central nervous system processes
      related to recognition, memory and habituation. Finally, our findings provide
      preliminary evidence to support the notion that the influence of prenatal stress
      and maternal-placental hormones on the developing fetus may persist after birth,
      as assessed by measures of temperament and behavioral reactivity in the first 3
      years of postnatal life. The implications of these studies for life-span
      development and health are discussed.

PMID- 11589127
TI  - Alterations in behavioral and neuroendocrine stress coping strategies in
      pregnant, parturient and lactating rats.
AB  - In the present chapter the behavioral and neuroendocrine alterations accompanying
      pregnancy and lactation will be discussed. It will be shown that many are
      dependent on the innate level of emotionality of the rats. In late pregnancy the
      level of anxiety, as measured on the elevated plus-maze is increased in rats with
      both high and low level of innate anxiety-related behavior, whereas lactating
      rats display less anxiety in such tests and higher degrees of aggressive behavior
      in tests for agonistic behavior. There is a dramatic reduction in the
      responsiveness of the hypothalamo-pituitary-adrenal (HPA) axis to various
      physical or emotional stimuli in both pregnant and lactating rats. This appears
      to be due to changes throughout the HPA axis. Oxytocin has been implicated in the
      control of the axis at this time, but the inhibitory action of central oxytocin
      on ACTH or corticosterone secretion seen in virgin female rats is not evident
      during pregnancy and lactation. However, central oxytocin is involved in the
      regulation of emotionality at this time. In addition to its anxiolytic effect,
      prolactin, acting at brain prolactin receptors, seems to exert an inhibitory
      effect on HPA axis responsiveness. At the time of parturition, the HPA axis is
      not stimulated by parturition-related stimuli and is under strong inhibition by
      endogenous opioids as revealed by the application of the opioid receptor
      antagonist naloxone.

PMID- 11589128
TI  - The actions of prolactin in the brain during pregnancy and lactation.
AB  - The vital role played by prolactin during pregnancy and lactation is emphasized
      by the physiological adaptations that occur in the mother to maintain a prolonged
      state of hyperprolactinemia. In many species the placenta provides a source of
      lactogenic hormones in the circulation, ensuring the continued presence of a
      hormone capable of activating the prolactin receptor throughout pregnancy. In
      addition, the tuberoinfundibular dopamine neurons, which normally maintain a
      tonic inhibitory influence over prolactin secretion, show a reduced ability to
      respond to prolactin during late pregnancy and lactation, allowing high levels of
      prolactin to be maintained unopposed by a regulatory feedback mechanisms. There
      is clear evidence that systemic prolactin gains access to the cerebrospinal
      fluid, from where it can diffuse to numerous brain regions. Prolactin receptors
      are expressed in several hypothalamic nuclei, including the medial preoptic and
      arcuate nuclei, and we have observed marked increases in expression of prolactin
      receptors in these nuclei during lactation. Moreover, a number of hypothalamic
      nuclei, including the paraventricular, supraoptic and ventromedial nuclei, in
      which prolactin receptors were not detected in diestrous rats, were found to
      express significant amounts of prolactin receptor during lactation. These
      observations have important implications for the variety of documented actions of
      prolactin on the brain. Prolactin has been reported to influence numerous brain
      functions, including maternal behavior, feeding and appetite, oxytocin secretion,
      and ACTH secretion in response to stress. In light of the high circulating levels
      of prolactin during pregnancy and lactation and the increased expression of
      prolactin receptors in the hypothalamus, many of these effects of prolactin may
      be enhanced or exaggerated during lactation. Hence, prolactin may be a key player
      in the coordination of neuroendocrine and behavioral adaptations of the maternal
      brain.

PMID- 11589130
TI  - Non-metabolic and metabolic factors causing lactational anestrus: rat models
      uncovering the neuroendocrine mechanism underlying the suckling-induced changes
      in the mother.
AB  - Follicular development and ovulation are strongly inhibited during lactation.
      Administration of a high dose of estrogen induces luteinizing hormone (LH) surges
      in ovariectomized lactating rats, suggesting that brain mechanisms regulating
      cyclic LH release remain intact in lactating mothers. On the other hand, tonic LH
      release is profoundly suppressed in lactating rats. This suggests that
      lactational anestrus is mainly due to suppression of the mechanism regulating
      pulsatile gonadotropin-releasing hormone secretion in the hypothalamus, which is
      responsible for follicular development and steroid production. Both metabolic and
      non-metabolic factors are involved in suppressing pulsatile LH secretion
      throughout lactation in rats. During the first half of lactation, pulsatile LH
      secretion is strongly suppressed, even if milk production is attenuated by
      pharmacological blockade of prolactin secretion in ovariectomized lactating rats.
      Pulsatile LH release quickly recovers by removing pups or blocking neuronal input
      by hypothalamic deafferentation during the period. These data suggest that the
      suckling stimulus itself is responsible for suppression of LH release during the
      first half of lactation. During the second half of lactation, negative energy
      balance, which is caused by the milk production, appears to play a dominant role
      in suppressing LH secretion. Blockade of milk production by inhibiting prolactin
      release causes a gradual increase in LH release even if the vigorous suckling
      stimulus by foster pups remains. In conclusion, the suckling stimulus itself
      predominantly suppresses LH pulses during the first half of lactation and
      metabolic factors take over the role of the suckling stimulus during the second
      half of lactation.

PMID- 11589129
TI  - Regulation of prolactin secretion during pregnancy and lactation.
AB  - Prolactin plays major roles in maintaining the corpora lutea of pregnancy and in
      the synthesis of milk during lactation. The hypothalamic mechanisms involved in
      these functions have been investigated. Mating leads to a surge of prolactin and
      programs daily surges during early pregnancy. The expression of Fos
      immunoreactivity shows that mating activates several hypothalamic nuclei,
      particularly the arcuate nucleus and medial preoptic area. In the arcuate
      nucleus, mating is associated with Fos expression in beta-endorphin neurons, and
      infusion of naloxone blocks both mating-induced and diurnal prolactin surges.
      Tyrosine hydroxylase-immunoreactive dopamine neurons appear not to participate in
      surge generation. However, after day 10 of gestation the secretion of placental
      lactogens suppresses prolactin secretion via activation of dopamine neurons
      without involvement of beta-endorphin neurons. Intracerebroventricular
      implantation of placental lactogen-secreting cells will block pregnancy prolactin
      surges, increase Fos expression in dopamine neurons, and increase tyrosine
      hydroxylase activity. During lactation the mechanisms regulating dopamine and
      beta-endorphin neurons are further modified. In early lactation a prolactin
      induced increase in tyrosine hydroxylase activity leads to negative feedback, but
      this effect is lost by mid-lactation. Overriding this negative feedback is the
      inhibitory effect that suckling has on dopaminergic activity. This may involve
      beta-endorphin-mediated inhibition of dopamine neurons, as naloxone causes a
      marked increase in tyrosine hydroxylase activity and suppression of circulating
      prolactin. However, removal of tonic dopamine inhibition is not sufficient to
      account for the high levels of prolactin attained during lactation, and
      additional releasing factors are probably involved. In situ hybrization
      histochemistry for the most recent candidate, prolactin-releasing peptide,
      suggests that this may involve brain stem neurons that co-localize noradrenaline.
      Thus, prolactin secretion during pregnancy and lactation involve complex
      interactions of regulatory factors and plasticity of neuronal responsiveness.

PMID- 11589131
TI  - Neuroendocrine changes and fertility in breast-feeding women.
AB  - Breast-feeding through the suckling stimulus suppresses fertility for a variable
      time after birth. Initially there is a period of pituitary gonadotroph recovery
      from the suppressive effects of the high steroid levels of pregnancy, followed by
      a period of suppressed ovarian activity associated with limited follicle growth.
      During this period of breast-feeding-induced amenorrhea, the pulsatile secretion
      of luteinizing hormone (LH), which reflects hypothalamic gonadotropin-releasing
      hormone (GnRH) release, is erratic and much slower than the one pulse per hour
      required in the normal follicular phase of the menstrual cycle to drive follicle
      growth. At some time the suckling stimulus drops below a threshold resulting in a
      resumption of reasonably organized pulsatile LH secretion, which is associated
      with development of follicles and some steroid secretion. However, positive
      feedback of estradiol which triggers the preovulatory LH surge and ovulation
      appears to be blocked by continued suckling, until suckling is reduced further
      and positive feedback and ovulation resumes. Often while women continue to breast
      feed the first few ovulations and menses are associated with inadequate corpus
      luteum function, which would probably not support a pregnancy. Eventually normal
      menstrual cycles resume when suckling declines further. The duration of
      amenorrhea and subsequent period of inadequate luteal function varies greatly
      between mother-baby combinations, and in different societies. Exactly how the
      suckling stimulus reduces pulsatile secretion of GnRH/LH is not clear, although
      clinical studies do not support a role for opioids or dopamine. The role of
      prolactin remains uncertain since suckling releases both prolactin and suppresses
      GnRH release. Regardless of the precise mechanism, it is clear that breast
      feeding in women can suppress fertility for prolonged periods, and women may
      proceed from pregnancy through lactation to another pregnancy and lactation with
      no menstrual period for several years.

PMID- 11589132
TI  - Food intake and leptin during pregnancy and lactation.
AB  - Successful reproduction requires the accumulation of energy reserves. Although
      acute and chronic food deprivation disrupts reproduction, surprisingly, an over
      abundance of energy reserves can also result in infertility. The infertility of
      obese, ob/ob mice can be reversed by the reintroduction of leptin, the protein
      product of the ob gene. In rats, energy reserves are increased during pregnancy
      by far accumulation and during lactation by hyperphagia. We have therefore
      investigated the interactions of leptin and food intake during late pregnancy and
      lactation in rats. Cycling rats consume their daily food intake during the dark
      phase and this is accompanied by a subsequent increase in plasma leptin
      concentration compared to light levels. During late pregnancy, rats increase
      their food intake during the dark phase and this is accompanied by a nocturnal
      increase in plasma leptin level. However, the nocturnal increase is not seen on
      the day prior to parturition, and is absent throughout lactation. Surprisingly,
      despite the massive increase in food intake during lactation plasma leptin levels
      continue to fall, suggesting that leptin release in response to food intake is
      suppressed during lactation. Furthermore, central leptin administration is less
      effective in reducing food intake in late pregnant and early lactating rats
      compared to cycling rats which suggests that these rats are insensitive to
      leptin. This may result from downregulation of brain leptin receptors. Decreased
      leptin production and action during late pregnancy and lactation will result in a
      decreased satiety effect, with up-regulation of orexigenic factors that produce
      hyperphagia, so allowing adequate energy intake for successful rearing of
      offspring.

PMID- 11589133
TI  - Relaxin and drinking in pregnant rats.
AB  - Work reported in this chapter describes the potential role of relaxin in
      resetting cardiovascular thresholds in pregnant rats. Relaxin, a polypeptide
      produced primarily by the ovary in pregnant animals in many species, is also
      produced in the brain. Exogenous administration of relaxin into the brain causes
      a profound drinking response which is negated by pretreatment with a specific
      monoclonal antibody to rat relaxin when the antibody is injected into the brain.
      Neutralizing the action of endogenous brain relaxin in pregnant rats also blocks
      the normal increase in drinking that is observed in rats at night during the
      second half of pregnancy. Relaxin acts through the forebrain angiotensin system
      at the level of the subfornical organ (an important interface between the blood,
      the brain and the cerebrospinal fluid) as blockade of the angiotensin II receptor
      action negates several central actions of relaxin. Expression of angiotensin II
      AT1 receptors in the subfornical organ increases in parallel with the increase in
      circulating relaxin seen in the second half of pregnancy. Neutralizing the
      effects of endogenous brain relaxin, using central injections of the monoclonal
      antibody, blocks this increase in the expression of angiotensin II AT1 receptors
      in subfornical organ. These data imply that relaxin in the brain may act to
      affect central cardiovascular thresholds in rats and this may be important for
      the normal physiology of pregnancy.

PMID- 11589134
TI  - Neuroendocrine and emotional changes in the post-partum period.
AB  - As well as having widespread effects on many aspects of mammalian physiology, the
      hormones of both the reproductive and stress axes can directly and indirectly
      influence behavior. Here we review possible mechanisms through which centrally
      active hormones of the female reproductive system and the hypothalamo-pituitary
      adrenal stress axis may interact to influence behavior and mood states during the
      post-partum period. We will focus primarily on the behavioral effects of selected
      neuropeptide hormones, in particular oxytocin, vasopressin and corticotrophin
      releasing hormone. The literature documenting central behavioral effects of these
      neuropeptides arises almost exclusively from research in experimental animals. In
      particular, it has been reported that during lactation in rats there are high
      blood and brain levels of oxytocin. At the same time there is a reduction in
      corticotrophin-releasing hormone in the brain and in its secretion in response to
      stress. These changes may contribute to optimal maternal care of the offspring.
      Correlational studies of peptides and behavior in the post-partum period also
      support the hypothesis that neuropeptides may influence human physiology and
      behavior. Studies of post-partum women reveal powerful regulatory effects of
      lactation on the reactivity of the hypothalamo-pituitary-adrenal axis and of
      autonomic and immune systems, especially in the face of challenge. The
      integrative function of neural systems that influence both reproduction and the
      hypothalamo-pituitary-adrenal axis suggests one central mechanism for mediating
      the effects of environmental challenges.

PMID- 11589135
TI  - Lactogenic hormone regulation of maternal behavior.
AB  - Biological factors can profoundly affect a mother's response to her young. For
      example, it is well known that the hormones of pregnancy act on the maternal
      brain to stimulate the spontaneous onset of maternal behavior at parturition.
      Studies in the rat have provided an excellent model to investigate maternal
      behavior in mammals, since maternal behavior in rats is easily observable and
      readily quantifiable and it is well-documented that the endocrine state of
      gestation helps to bring about the onset of maternal behavior around the time of
      birth. The same response in virgin animals requires a number of days of constant
      exposure to pups before maternal-like behaviors emerge. To date, research has
      established that the steroid hormones, estradiol and progesterone, and the
      lactogenic hormones, prolactin and the placental lactogens, act in concert to
      stimulate maternal behavior in the pregnant female. Treatment of adult, virgin
      rats with these hormones can stimulate a rapid onset of maternal care. In the
      present chapter experiments are described that demonstrate key roles for
      prolactin and placental lactogens in the onset of maternal behavior. Central
      sites of action of prolactin and placental lactogens, including the medial
      preoptic area, appear to be involved in stimulating the onset of maternal care.
      Other studies are discussed which support the involvement of the prolactin
      receptor in the endocrine regulation of maternal behavior using prolactin
      receptor antagonist and 'knock-out' models in rats and mice, respectively.
      Overall, these studies indicate that during pregnancy the endocrine system primes
      the mother's brain so that the new mother displays appropriate and successful
      behaviors toward her newborn at parturition.

PMID- 11589136
TI  - Neural mediation of nursing and related maternal behaviors.
AB  - Nursing is the behavioral concomitant of lactation and the most generalizable
      maternal behavior across mammals. In lactating rats nursing often occurs in the
      kyphotic (upright crouched) posture; like the neuroendocrine determinants of milk
      synthesis and release, kyphosis requires suckling by the young. The dam's active
      pronurturant behaviors, such as retrieval and licking of pups, requires perioral
      somatosensory stimulation, which is often a precursor of kyphosis as well, and is
      inhibited by suckling. The sequential nature of maternal behaviors and the
      dissociations in their somatosensory regulation are critical to understanding
      their neural mediation, as exemplified by our recent work in lactating rats. We
      found that the caudal lateral and ventrolateral midbrain periaqueductal gray
      (cPAGl,vl) is a sensorimotor integration site for the kyphotic nursing posture.
      Destruction of the cPAGl,vl, or increased activity of the inhibitory
      neurotransmitter GABA within it, severely reduced kyphosis, increased nursing in
      more atypical postures, and had little or no effect on pronurturance. Various
      forebrain sites are known to mediate retrieval and licking of pups. Inhibition of
      dopaminergic activity in the nucleus accumbens of dams via microinfusions of a
      mixed D1/D2 dopamine receptor antagonist, cis-flupenthixol (FLU), dose
      dependently reduced these active behaviors, while increasing nursing duration.
      Retrieval was inhibited, however, only by infusions of FLU that included the
      nucleus accumbens shell, which is reciprocally connected with other sites
      implicated in retrieval of pups. Thus, maternal behavior is not a unitary process
      but rather a complex category consisting of sequential behavioral components that
      have their own sensory and neural determinants.

PMID- 11589137
TI  - Genomic imprinting and the maternal brain.
AB  - Those parts of the genome that contain imprinted genes are relatively small
      (between 100 and 150 genes predicted) but their impact on mammalian development
      and evolution is substantial. Most of the imprinted genes that have been studied
      are regulatory: transcription factors, alternative splicers, oncogenes, tumor
      suppressors, growth factors, or are involved in complex signalling pathways such
      as the tumor necrosis factor (TNF) and ubiquitin pathways. This review considers
      the effects of imprinted genes on brain development by examining the distribution
      of androgenetic and parthenogenetic cells in the brains of chimeric mice using in
      situ markers. At birth, cells that are disomic for the paternal genome
      (androgenetic) contribute substantially to the hypothalamus, septum, preoptic
      area and bed nuclei of the stria terminalis and fail to survive in the developing
      neocortex and striatum. In contrast, cells that are disomic for the maternal
      genome (parthenogenetic) proliferate in the cortex and striatum but are excluded
      from the diencephalic structures. Growth of the brain is enhanced by the presence
      of parthenogenetic cells and hence increased maternal gene dosage, whereas the
      brains of androgenetic chimeras are smaller. Mest and Peg3, two imprinted genes
      that are paternally expressed, have been disrupted by gene targeting and show
      high levels of expression in regions where androgenetic cells accumulated, namely
      the hypothalamus, preoptic area and septum. Although of different structural
      classes and located on different chromosomes, both of these paternally expressed
      genes influence placental growth and maternal behavior. The implications of these
      findings for brain evolution and maternal behavior are discussed.

PMID- 11589138
TI  - Like mother, like daughter: evidence for non-genomic transmission of parental
      behavior and stress responsivity.
AB  - Considerable evidence demonstrates that the quality of the early environment
      influences patterns of development that, in turn, determine the health and
      productivity of the individual throughout their life span. However, the processes
      through which early life influences health are not clearly understood. Through
      the activation of the hypothalamo-pituitary-adrenal (HPA) axis and corticotropin
      releasing hormone (CRH) pathways, prolonged or exaggerated responses to stress
      have profound effects on physiological and cognitive functions. Early maternal
      separation or handling of neonatal rats can program widespread and lifelong
      changes in various transmitter systems that regulate the HPA and CRH systems. Our
      studies show that a high level of maternal licking/grooming, and arched-back
      nursing correlates with reduced CRH mRNA expression and enhanced glucocorticoid
      negative feedback, and lower stress responses in the adult. This behavior is
      stably transmitted between generations and cross-fostering studies show that the
      offspring inherit the behavior from the nursing mother and not the biological
      mother. Such intergenerational transmission of maternal behavior is seen in
      rodents, primates and humans, and may underlie adaptive changes in the HPA axis.
      The neural basis of this inheritance pattern appears to reside in the central
      oxytocin system which determines features of maternal behavior. Through these
      various adaptive neural mechanisms the environmental demand on the mother is
      reflected in the quality of maternal care to her offspring. This, in turn,
      programs stress reactivity and maternal behavior patterns of the offspring. This
      not only determines certain health outcomes but also establishes the
      relationships between mother and offspring in the next generation. These findings
      suggest that for neurobiologists, the function of the family is an important
      level of analysis and the critical question is that of how environmental events
      regulate neural systems that mediate the expression of parental care.

PMID- 11589139
TI  - Pregnancy and post partum: changes in cognition and mood.
AB  - Steroidal hormones are increasingly recognized as highly relevant in multiple
      aspects of brain functioning. While basic science has actively worked to advance
      understanding of fundamental steroid mechanisms within the brain, investigation
      of the neurobehavioral outcomes of reproductive hormone actions on the human
      brain has received less attention. We argue that the dramatic steroidal hormone
      changes seen in human reproduction must be systematically studied and may provide
      novel explanations of cognitive and mood disorders associated with reproductive
      events. This chapter provides a review of current literature establishing a role
      for a variety of steroids on neuroactivity, and evidence from a variety of
      observational and experimental paradigms linking hormones and clinical aspects of
      cognition and mood in humans. The specific hormonal changes of pregnancy are
      described and discussed in relation to concomitant alterations in cognition and
      mood across the peri-natal period. A review of studies that have systematically
      observed cognitive and affective changes both during pregnancy and the post
      partum period is presented, as well as new data that follow a small cohort of
      women for an extended period of time after delivery. We conclude that women may
      show specific areas of cognitive changes during and after pregnancy, notably
      deficits in verbal learning and memory. Mood appears to be impacted as well.
      While steroidal hormones show a pattern of associations with mood during and
      after pregnancy, no such pattern is evident for cognition. The embryonic state of
      our knowledge regarding reproductive hormones and neurobehavioral functioning is
      evident, as are the scientific and public health reasons to redress this lacuna.

PMID- 11589140
TI  - Molecular genetic approaches to puerperal psychosis.
AB  - Puerperal psychosis, an episode of mania or psychosis precipitated by childbirth
      follows approximately one in 1000 deliveries. The evidence of clinical, outcome
      and genetic studies supports the hypothesis that the majority of puerperal
      psychotic episodes are manifestations of an affective disorder diathesis with a
      puerperal trigger. Furthermore the available evidence supports the hypothesis
      that genes are involved in susceptibility to both diathesis and trigger. For
      complex genetic disorders such as affective illness there are marked benefits in
      focussing on a homogeneous subtype which allows a subset of hypotheses to be
      tested. Molecular genetic studies of puerperal psychosis provide an excellent
      example of this strategy, allowing a hierarchy of hypotheses concerning the
      involvement of neurosteroid pathways in pathophysiology to be tested. Puerperal
      psychosis results in considerable suffering to a woman and her family.
      Elucidating the pathophysiological basis of this disorder will lead to better
      prevention and treatment and, it is anticipated, inform research on affective
      disorders more generally.

PMID- 11589141
TI  - The maternal brain as a model for investigating mental illness.
AB  - The idea that a particular type of severe mental illness, puerperal or post
      partum psychosis, is a disease entity and that its causes lie in some kind of
      physiological disturbance of the reproductive process, can be traced back to
      antiquity. Epidemiological studies provide strong support for such an hypothesis,
      but, despite the powerful methodological attractions of using childbirth as a
      model for research, there has been surprisingly little neuroendocrine research
      into this subject. There have been preliminary reports of prospective research
      into women with histories of affective psychosis who are pregnant and who are at
      particularly high risk of recurrence of illness. This work suggests that it may
      be very fruitful to investigate interactions between the massive changes that
      occur in sex hormones around parturition and the activity of selected
      neurotransmitter systems. Because of the prospective research paradigm, it
      becomes possible to test whether the measures can predict who will become ill and
      who will stay well.

PMID- 11589142
TI  - An appreciation of Professor Ramesh Kumar (1938-2000).

PMID- 11589143
TI  - Physiological roles for the neurosteroid allopregnanolone in the modulation of
      brain function during pregnancy and parturition.
AB  - Allopregnanolone is a well-established allosteric modulator of the GABAA receptor
      but its physiological roles within the nervous system remain unclear. Derived
      principally from circulating progesterone, allopregnanolone achieves its highest
      concentrations within the nervous system during late pregnancy and recent studies
      have now begun to elucidate its roles at this time in the rat. At the molecular
      level it is clear that the regulation of GABAA receptor subunit gene expression
      by progesterone and its derivatives occurs in a subunit- and a neuron-specific
      manner and that both progesterone and allopregnanolone are involved. At the
      cellular level, the increasing concentrations of allopregnanolone with advancing
      pregnancy can be shown to have important physiological actions in repressing the
      electrical activity of specific neuronal phenotypes such as the magnocellular
      oxytocin neurons. The marked fall in progesterone and allopregnanolone
      concentrations prior to parturition equally appears to have a substantial impact
      upon GABAA receptor signaling in the hippocampus, frontal cortex and oxytocin
      neurons. Together, studies at a basic level suggest that the rise and fall in
      allopregnanolone concentrations during pregnancy are likely to exert a powerful
      regulatory influence upon neurotransmission in a variety of brain networks. The
      temporal correlation between these events and the observed cognitive, psychiatric
      and physiological changes associated with pregnancy and the peri-partum period in
      humans is striking and warrants close attention.

PMID- 11589144
TI  - Maternity leads to morphological synaptic plasticity in the oxytocin system.
AB  - The oxytocinergic system, which plays a major role in the control of different
      aspects of maternity, undergoes extensive synaptic and neuronal-glial remodelling
      during parturition and lactation and has thus become a remarkable example of
      activity-dependent morphological synaptic plasticity in the adult mammalian
      brain. The use of different comparative ultrastructural analyses on the rat
      supraoptic and paraventricular nuclei, together with identification of pre- and
      post-synaptic elements, has allowed us to show that there is a significant
      increase in the number of GABAergic, glutamatergic and noradrenergic synapses
      impinging on oxytocin neurons, concomitant with a reduction of glial coverage of
      the neurons. This synaptic plasticity involves axo-dendritic and axo-somatic
      contacts originating from terminals making one or several synaptic contacts in
      one plane of section. While noradrenergic afferents arise from medullary
      catecholaminergic neurons, our recent in vitro observations indicate that
      GABAergic and glutamatergic afferents derive, at least partly, from local
      intrahypothalamic neurons, in close proximity to oxytocin neurons. The cellular
      mechanisms underlying this morphological synaptic plasticity remain to be
      determined but it is highly likely that they depend on increased activity in both
      pre- and post-synaptic elements. Moreover, the oxytocin system continues to
      express 'embryonic' molecular features that may allow the morphological
      plasticity to occur. In particular, it expresses high levels of cell surface
      adhesion molecules currently thought to intervene in synaptic remodelling in the
      developing and lesioned central nervous system, including the weakly adhesive
      polysialylated isoform of the Neural Cell Adhesion Molecule, the axonal
      glycoprotein F3 and its ligand, the extracellular matrix glycoprotein, tenascin
      C.

PMID- 11589145
TI  - Oxytocin: who needs it?
AB  - The neuropeptide oxytocin has been implicated in the initiation of maternal
      behavior, based on studies in rats and sheep. Females in both of these species
      naturally avoid infants until parturition when they begin to show an intense
      interest in maternal care. Oxytocin pathways in the brain appear to be important
      for this transition from avoidance to approach of the young. Recent studies in
      mice with a null mutation of the oxytocin gene suggest a different scenario.
      These mice, which completely lack oxytocin, exhibit full maternal and
      reproductive behavior, except for a deficit in milk ejection. Apparently,
      oxytocin is not essential for maternal behavior in this species. Consistent with
      the role of oxytocin for the transition from avoidance to approach in rats and
      sheep, nulliparous mice show full maternal behavior and therefore do not require
      the peptide for the initiation of maternal care. The species differences in the
      behavioral effects of oxytocin are associated with profound species differences
      in the location of oxytocin receptors in the brain. Recent transgenic studies
      suggest that these species differences in the neuroanatomical distribution of
      oxytocin receptors may be a function of inter-species variation in the flanking
      region of the oxytocin receptor gene. So, who needs oxytocin? For maternal care,
      not mice and (possibly) other species, like primates, with promiscuous parental
      care. Most important, in considering the behavioral or cognitive functions of
      oxytocin, one cannot accurately extrapolate across species unless one knows the
      species have the same neuroanatomical location of oxytocin receptors.

PMID- 11589146
TI  - Endogenous opioid regulation of oxytocin and ACTH secretion during pregnancy and
      parturition.
AB  - Progress of parturition in the rat is optimal when there is increased oxytocin
      secretion, thus ensuring quick birth and otherwise risking adverse neonatal
      health. To ensure that the mechanisms for this are available, oxytocin neurons
      adapt in pregnancy and this includes development of a tonic inhibition by
      endogenous opioids. Endogenous opioid inhibition of oxytocin secretion increases
      in pregnancy, initially acting on the nerve terminals in the posterior pituitary
      and later on oxytocin cell bodies and their inputs. This inhibition enhances
      stores of oxytocin and enables restraint of oxytocin neuron responsiveness to
      selected excitatory inputs. The hypothalamic neurons which mediate stress also
      adapt in late pregnancy so that hypothalamo-pituitary-adrenal axis and oxytocin
      secretory responses to stressor exposure are attenuated. This is also partly due
      to endogenous opioid inhibition. Thus, in pregnancy oxytocin and hypothalamo
      pituitary-adrenal axis secretion in response to stimulation is restrained,
      protecting the unborn fetus(es) from premature delivery and glucocorticoid
      exposure and preparing the oxytocin neurons for their important secretory role
      during parturition. In parturition itself, endogenous opioids continue to inhibit
      these neurons. Stress exposure during parturition delays births, probably due to
      endogenous opioid inhibition of pulsatile oxytocin secretion. On the other hand,
      basal ACTH and corticosterone secretion are reduced in parturition through
      inhibition by endogenous opioids. So, opioids continue to regulate the activity
      of oxytocin and hypothalamo-pituitary-adrenal mechanisms in labor; inhibition of
      oxytocin neurons at this time may control the spacing of pup births.

PMID- 11589147
TI  - The maternal spinal cord: biochemical and physiological correlates of steroid
      activated antinociceptive processes.
AB  - Physiological gestation, as well as the simulation of the associated changes in
      estrogen and progesterone, is associated with significant elevations in
      nociceptive response thresholds. This is mediated by spinal cord kappa- and delta
      opIoid systems. The predominant spinal mu-opioid system does not appear to
      participate. One hallmark of pregnancy- and hormonally-induced antinociception is
      the multiplicative interaction among its components. Approximately 40% results
      from spinal kappa/delta analgesic synergy on which is superimposed an additional
      increment (approximately 60%) of synergy that results from the interaction
      between descending spinal alpha 2-noradrenergic and spinal kappa/delta
      activities. An intact hypogastric nerve is required for the spinal alpha 2
      noradrenergic component. This would explain the requirement for an intact
      hypogastric nerve in order for the antinociception of pregnancy and its hormonal
      simulation to be fully manifest. The predominant means by which spinal dynorphin
      containing neurons adjust to increased demand is increased post-translational
      processing of dynorphin precursor intermediates which are present at
      approximately 10x the concentration of mature dynorphin peptides (1-17 and 1-8).
      This is indicated by the concomitant decline (approximately 50%) in the spinal
      cord content of dynorphin precursors and increase (approximately 87%) in the
      content of prohormone convertase 2, a processing enzyme sufficient to generate
      mature dynorphin peptides from prodynorphin. The presence of 'high gain'
      multiplicative spinal opioid antinociceptive pathways that can be activated by
      estrogen and progesterone has hyperalgesic implications as well, i.e. it could
      result in disproportionately increased pain responsiveness. This might explain,
      in part, findings that women are more prone to recurrent pain and pain of greater
      duration and intensity than men. The underlying mechanisms of gestational
      antinociception could point the way to pain pharmacotherapies that are gender
      based.

PMID- 11589148
TI  - Hypothalamic and limbic expression of CRF and vasopressin during lactation:
      implications for the control of ACTH secretion and stress hyporesponsiveness.
AB  - Lactation is associated with physiological and behavioral changes that optimize
      conditions for development of the offspring. Although neuroendocrine and
      emotional stress responses are blunted, the central mechanisms involved are
      unclear. In addition to a reduction in stimulatory noradrenergic inputs to
      paraventricular nucleus (PVN) neurons, we demonstrate that lactation induces: (1)
      unique phenotypic changes in neuropeptide expression by hypothalamic PVN neurons
      (reduced expression of corticotropin-releasing factor (CRF) mRNA and increased
      expression of vasopressin mRNA in parvocellular PVN neurons); and (2) changes in
      pituitary sensitivity to CRF (reduced) and vasopressin (increased) as a
      consequence of differential CRF/vasopressin secretion into the hypophysial portal
      blood. Neurons in the bed nucleus of the stria terminalis (BNST) and the central
      amygdala (CeA) that are implicated in the control of the hypothalamopituitary
      adrenal axis also display changes in lactation: expression of CRF mRNA in the CeA
      is reduced, consistent with the diminished responsiveness to acoustic startle
      observed in nursing mothers. In contrast, expression of CRF mRNA is increased in
      the dorsolateral portion of the BNST, probably because of the tonic increases in
      endogenous glucocorticoid production during this period. Using immuno-targeted
      lesions of CRF or vasopressin in the PVN of virgin females, we have shown that
      CRF neurons of the PVN send inhibitory projections to the dorsolateral portion of
      the BNST and stimulatory inputs to CRF neurons in the CeA. Thus, it is possible
      that lactation-induced changes in the activity of parvocellular PVN neurons might
      also modulate the expression of neuropeptides and neurotransmitters in the BNST
      and the amygdala.

PMID- 11589149
TI  - [Optimization of the functional state of air traffic controllers on the night
      shift].
AB  - To optimize the functional state of air traffic controllers on the night shift a
      program of combined vibroelectrical stimulation of active points on the skin
      repeated every 2 hours without assistance has been developed. The test group and
      the control group included 28 and 21 employees, respectively. The positive effect
      was expressed by statistically significant improvement of the objective
      parameters of job efficiency, functional state and performance, and the
      activities of physiological regulation and metabolism.

PMID- 11589150
TI  - [Meta-analysis of the cumulative effects of piloting G-loads on the cervical
      vertebrae].
AB  - On the data of meta-analysis performed in 10 independent Russian and
      international studies of the cumulative effects of piloting g-loads on
      functioning of the vertebral column cervical segment, the conclusion has been
      made concerning a statistically significant linkage between the degenerative
      dystrophic diseases of the vertebral column and regular exposure to the +Gz
      loads.

PMID- 11589151
TI  - [The combined effect of retabolile and support loads on the post-traumatic
      reparation process in suspended rat muscles].
AB  - Histological and histomorphometric technical were used to determine effects of
      limited support loads and anabolic steroid retabolite on the time course of the
      post-traumatic reparation of m. soleus and m. gastrocnemius in tail-suspended
      rats in the 14-d experiment. One day prior to suspension, the muscles were partly
      crushed after the rats had been anesthetized with the help of artery clamp.
      Deprivation of the support loading was shown to cause atrophy of m. soleus and,
      to a less degree, m. gastrocnemius and inhibit the post-traumatic reparation of
      m. soleus. Neither retabolite injection (at the total dose of 5 mg per 100 g of
      the body mass) nor daily limited support loading (the rats were free from
      suspension and could stand on all four limbs 2 hrs a day) could essentially
      prevent muscle atrophy and enhance reparation. Nonetheless, combination of the
      support loads with retabolite injection implicitly slowed atrophy and stimulated
      healing of m. soleus trauma.

PMID- 11589153
TI  - [Periods in the working cycle and morbidity of submarine personnel on long-term
      self-sufficient cruises].
AB  - The authors review literature dedicated to the attempts at defining periods
      within the working cycle of nuclear submarine personnel on long-term self
      sufficing cruises, and propose own definition of periods. Characteristics of the
      epidemiological process in pressurized vehicles are described. The general
      morbidity is presented in values of an intensive index. Consideration is given to
      the incidence of infectious, skin and subcutaneous fat diseases, and
      microtraumata.

PMID- 11589152
TI  - [Stimulation of bone fracture healing in rats under the support load deficit].
AB  - Experiment with rats the hind limbs of which were deprived of support loads (tail
      suspension) for two weeks following operational fracture of fibular bones
      evidenced inhibited callus formation and lowered strength of bone fragments
      consolidation. Injection of anabolic steroid retabolite to the traumatized
      animals together with limited support loading was favorable to the bone callus
      formation and consolidation of fragments. This measure also distinctly increased
      the functional activity of adenohypophysial somatotrophs (growth hormone
      producers) and thyroid C-cells (calcitonine producers). The direct dependence of
      bone fracture healing on the somatotropic function of the adenohypophysis
      suggests that the favorable effect of retabolite combined with the support
      loading is at least partly achieved through the somatorophic function of the
      adenohypophysis.

PMID- 11589154
TI  - [Prediction of the body resistance to chronic irradiation by different dose rates
      using the generalized logarithmic index].
AB  - Patterns of radiation damage development and reparation of the blood-forming
      system in mice and rats were outlined from calculated values of the generalized
      logarithmic index for chronic irradiation by different dose rates. Dynamics of
      the generalized index in the course of chronic irradiation makes the basis for
      predicting deviations in the resistance of animals during next irradiation
      session.

PMID- 11589155
TI  - [Gas exchange intensity: relation to the body radiation resistance].
AB  - In the absence of immobilization stress gas exchange in rats does not increase in
      response to exposure to 6 to 13 Gy. Oxygen uptake intensity by intact animals at
      room and low ambient temperature is a stable individual characteristic positively
      correlating with life span following acute bone marrow irradiation. It is
      hypothesized that high gas exchange in radioresistant animals is linked with high
      inherent DNA synthesis and reparation. In animals experiencing immobilization
      stress the correlation between gas exchange reactivity and body radioresistance
      is supposed to be a result of more intensive uptake of oxygen diffusing in cells
      and consequent reduction in nucleus oxygenation and mitigation of DNA radiation
      induced damage.

PMID- 11589156
TI  - [Effect of argon and nitrogen on the peritoneal macrophages in mice and their
      resistance to the UV damaging effect in vitro].
AB  - Explored were effects of argon and nitrogen on intracellular pH in peritoneal
      macrophages in mice and resistance of cellular membranes to the UV damaging
      effect in vitro. Blasting argon or nitrogen along the surface of cell cultures in
      airtight chamber for 20 minutes was shown to decrease 5-folds the oxygen content
      of solution as compared with initial level with culture pH unchanged. Ten-minute
      blasting argon or nitrogen through the incubation chamber slightly elevates
      intracellular pH in macrophages. The standard cell incubation conditions
      recovered following approximately 60 minutes in hypoxic atmosphere, the ability
      of macrophages to build up fluorescein was degraded and they increased
      intracellular pH no matter the indifferent gas yet more marked in case of
      nitrogen in use. It was demonstrated that the normobaric gas environment with
      oxygen partly replaced by nitrogen or argon protects plasmatic membranes of cells
      from UV-induced damage.

PMID- 11589158
TI  - [The model of statoconia distribution in the gravity receptors of shells in
      ontogenesis].
AB  - Based on the experimental data of Wiederhold et al., analyzed was distribution of
      statoconia in gravireceptors of Biomphalaria glabrata and Aplysia californica in
      ontogenesis. A mathematical model of size distribution of statoconia in statocyst
      Biomphalaria glabrata in ontogenesis has been developed. Growth of statoconia in
      size is described as a process of crystallization from solution. Hypothetically,
      redistribution of statoconia in ontogenesis is determined by generation of new
      statoconia and their linear growth in size. Comparison of the resultant
      analytical solution of the model with published experimental data revealed a
      number of characteristic stages in statoconia development. Generation of new
      statoconia if peculiar for stage 1 and proceeds till the shell diameter (D)
      becomes as large as 4 mm. At D > 6 mm, statoconia distribution is driven by their
      size growth at a permanent rate. In the interval of delta D = 4-6 mm, statoconia
      undergo redistribution which is probably connected with selective dissolution of
      big statoconia and ensuing period of linear growth. The model is in good
      agreement with the literature on experimental data and, therefore, is
      instrumental in evaluation of changes in statoconia distribution. The authors
      laid out plans of further experiments in order to test the model of statoconia
      distribution in Biomphalaria glabrata in ontogenesis, and to get quantitative
      description of statoconia distribution in the gravireceptor of Aplysia
      californica in ontogenesis.

PMID- 11589157
TI  - [Growth and development of plants in a sequence of generations under the
      conditions of space flight (experiment Greenhouse-3)].
AB  - The purpose was to study characteristic features of growth and development of
      several plant generations in space flight in experiment GREENHOUSE-3 as a part of
      the Russian-US space research program MIR/NASA in 1997. The experiment consisted
      of cultivation of Brassica rapa L. in board greenhouse Svet. Two vegetative
      cycles were fully completed and the third vegetation was terminated on day 13 on
      the phase of budding. The total duration of the space experiment was 122 days,
      i.e. same as in the ground controls. In the experiment with Brassica rapa L.
      viable seeds produced by the first crop were planted in space flight and yielded
      next crop. Crops raised from the ground and space seeds were found to differ in
      height and number of buds. Both parameters were lowered in the plants grown from
      the space seeds. The prime course for smaller size and reduced organogenic
      potential of plantTs reproductive system seems to be a less content of nutrients
      in seeds that had matured in the space flight. Experiment GREENHOUSE-3
      demonstrated principle feasibility of plant reproduction in space greenhouse from
      seeds developed in microgravity.

PMID- 11589159
TI  - [Evaluation of the demographic situation in a town with oil refinery and chemical
      industries].
AB  - In recent years the problem of population health has been acquiring the character
      of a growing threat to national safety. This is grounded first of all on
      observation of changes in medical demographic indices, especially in ecologically
      disadvantaged regions among which are the Republic of Bashcortostan and its
      capital Ufa with large oil refinery and petrochemical enterprises. High
      population density and numerous oil refineries combined with the unfavorable
      meteoconditions are the factors of heavy pollution of the area with global and
      local ecotoxicants. Observations showed that the demographic situation had been
      turning tougher in urban, especially residential districts in the vicinity of
      refineries and petrochemical enterprises. Objective data were obtained indicative
      of aggravation of medical and genetic indices due to the chronically harmful
      environment, and socio-economic setback.

PMID- 11589160
TI  - [Human performance against acute alcohol intoxication].
AB  - Analyzed were quantitative literary data on the effects of acute alcohol
      intoxication on performance. Reviewed were impacts of various doses of alcohol on
      the psychophysiological parameters and intricate sensorimotor functions of flying
      human operator. Alcohol was found to be unfavorable to the vestibular function
      and, therefore, predisposing to traffic and flight accidents. Hence, the alcohol
      CNS effects give rise to behavioral and psychophysiological disturbances. The
      psychophysiological disturbances are impaired concentration and dynamic visual
      function as a whole, deteriorated light differentiation ability and information
      perception, short-term amnesia, altered alertness and block, and associated lack
      of self-criticism and self-control.

PMID- 11589161
TI  - [Specific aspects of hemostasis and lipid peroxidation in thrombocyte membranes
      during expedition and shift organization of labor].
AB  - The aim of the present study is to investigate dynamics of the hemostasis system
      and structural and functional state of thrombocyte membranes by the LPO and AOD
      parameters under the conditions of expedition and shift organization of labour of
      worker tripping from the West Siberia middle latitudes to the Far North. A trend
      to hypocoagulemia and increases in LPO and AOD reactions were characteristic of
      the type-1 (adaptive) reaction. The type-2 (hypotensive) reaction included a
      trend to hypercoagulemia, an increase in LPO and a decrease in AOD reactions in
      thrombocyte membranes as well as a hypertensive reaction during the whole shift
      period. The type-3 (asthenic) reaction was described by hypocoagulemia, an
      increase in the amount of LPO products with a simultaneous decrease in the AOD
      activity and asthenic sleep disturbance.

PMID- 11589162
TI  - [Morpho-functional status of the thyroid gland and large cell hypothalamus nuclei
      in the ionizing irradiation and ethanol].
AB  - Morphofunctional state of the thyroid and nuclei in the hypothalamic large cells
      was examined following exposure to ionizing radiation at the dose of 20 Gy
      without and with ethanol administration (2.25 g/kg) before or after exposure. The
      highest thyroid radioprotecting effect of the ethyl alcohol was achieved when
      introduced before exposure as it reduced apoptosis of thyrocytes and balanced the
      disturbances in colloid amino acids iodination. As for nuclei of the hypothalamic
      large cells, the radiomodifying effect of ethanol was synergic when introduced
      before and potential amplifying after the radiation exposure being manifested by
      distinct activation and ensuing overstrain and exhaustion of the neurosecretory
      cells. Analysis of the experimental data suggests causality of the thyroid
      protecting effect of ethanol by functional hyperactivation of supraoptic and
      paraventricular nuclei in the hypothalamus.

PMID- 11589163
TI  - Some recent developments in neonatal neurology.

PMID- 11589164
TI  - Visual disorders in children with brain lesions: 1. Maturation of visual function
      in infants with neonatal brain lesions: correlation with neuroimaging.
AB  - In the last two decades there has been a considerable increase in the
      understanding of visual maturation in the young infant and it has been possible
      to develop methods for testing visual function that are applicable in the
      neonatal period and early infancy. Several studies have reported that various
      aspects of visual function, such as visual acuity, visual fields and optokinetic
      nystagmus are often impaired in infants with brain lesions of antenatal and
      perinatal onset. We report our experience with such infants and a more general
      review of the literature on the maturation of visual function in the first years
      after birth in normal and brain damaged children.

PMID- 11589165
TI  - Visual disorders in children with brain lesions: 2. Visual impairment associated
      with cerebral palsy.
AB  - Disorders of visual function are a common finding in children with cerebral
      palsy. In some cases they are secondary to ophthalmologic abnormalities such as
      cataract or retinopathy, but more often they are due to damage of the central
      visual pathway. We review the literature on the prevalence and distribution of
      visual abnormalities in children with cerebral palsy and their relation to
      cognitive, motor and emotional development.

PMID- 11589166
TI  - Non-progressive leukoencephalopathy with bilateral temporal cysts.
AB  - We report two cases of a peculiar leukoencephalopathy with temporal cysts. Both
      patients have a non-progressive neurological disorder with mental retardation,
      microcephaly and sensorineural deafness although clinical differences between
      them may reflect a different aetiology. The metabolic disorders with white matter
      involvement and the recently described leukoencephalopathies (Van Der Knaap
      disease, 'vanishing white matter disease') were excluded based on clinical,
      biologic and imaging findings. Cytomegalovirus infection is a likely possibility
      in the first case although the magnetic resonance imaging picture is only
      partially similar to previously reported cases. Our patients are strikingly
      similar to the patients reported by Deonna et al. and Olivier et al. We discuss
      the clinical and imaging findings in our patients and the differential diagnosis
      considering the known disorders of the white matter in childhood.

PMID- 11589167
TI  - Congenital disorders of glycosylation (CDG) may be underdiagnosed when mimicking
      mitochondrial disease.
AB  - Congenital disorders of glycosylation (CDG) and mitochondrial diseases are
      multisystem disorders with clinical characteristics that may overlap. We present
      four patients with CDG whose phenotypes suggested the diagnosis of a
      mitochondrial disease. Patients 1 and 2 are siblings with hemiplegic headache,
      stroke-like episodes, lactic acidaemia and history of maternal migraine; their
      initial clinical diagnosis was MELAS syndrome (mitochondrial encephalopathy,
      lactic acidosis and stroke-like episodes). Patient 3 suffers from ataxia,
      neuropathy, ophtalmoplegia and retinitis pigmentosa suggestive of NARP
      (neuropathy, ataxia, and retinitis pigmentosa) syndrome. Patient 4 presented with
      neurological regression mimicking Leigh disease, with ptosis, myoclonus, ataxia
      and brainstem and cerebellar atrophy. Screening for mitochondrial disease
      including enzyme and mtDNA investigations on muscle biopsy were performed on
      Patients 1, 2 and 4 with normal results. However, evidence for a glycosylation
      disorder was substantiated by an increased carbohydrate deficient transferrin
      (CDT). The isoelectric focussing pattern of serum sialotransferrin was typical of
      CDG type I in Patients 1, 2 and 3 and was shifted towards the less sialylated
      bands in case 4. A deficiency of phosphomanomutase (PMM) confirmed the diagnosis
      of CDG-Ia in Patients 1, 2 and 3, who are compound heterozygous for mutations
      R141H/T237M (Patients 1 and 2) and R141H/P113L (Patient 3). In Patient 4, PMM
      activity was normal, and further enzymatic and molecular studies are underway. As
      the search for the primary defect in mitochondrial diseases is often
      unsuccessful, the pool of mitochondrial patients that remain without definite
      diagnosis might include CDG cases. Routine screening for CDG may avoid precocious
      invasive investigations.

PMID- 11589168
TI  - Nukes may be linked to hearing loss.

PMID- 11589169
TI  - In memoriam: Ariel G. Loewy (1925-2001).

PMID- 11589170
TI  - Clinical findings of West Nile virus infection in hospitalized patients, New York
      and New Jersey, 2000.
AB  - Outbreaks of West Nile (WN) virus occurred in the New York metropolitan area in
      1999 and 2000. Nineteen patients diagnosed with WN infection were hospitalized in
      New York and New Jersey in 2000 and were included in this review. Eleven patients
      had encephalitis or meningoencephalitis, and eight had meningitis alone. Ages of
      patients ranged from 36 to 87 years (median 63 years). Fever and neurologic and
      gastrointestinal symptoms predominated. Severe muscle weakness on neurologic
      examination was found in three patients. Age was associated with disease
      severity. Hospitalized cases and deaths were lower in 2000 than in 1999, although
      the case-fatality rate was unchanged. Clinicians in the Northeast should maintain
      a high level of suspicion during the summer when evaluating older patients with
      febrile illnesses and neurologic symptoms, especially if associated with
      gastrointestinal complaints or muscle weakness.

PMID- 11589171
TI  - Equine West Nile encephalitis, United States.
AB  - After the 1999 outbreak of West Nile (WN) encephalitis in New York horses, a case
      definition was developed that specified the clinical signs, coupled with
      laboratory test results, required to classify cases of WN encephalitis in equines
      as either probable or confirmed. In 2000, 60 horses from seven states met the
      criteria for a confirmed case. The cumulative experience from clinical
      observations and diagnostic testing during the 1999 and 2000 outbreaks of WN
      encephalitis in horses will contribute to further refinement of diagnostic
      criteria.

PMID- 11589172
TI  - West Nile virus infection in mosquitoes, birds, horses, and humans, Staten
      Island, New York, 2000.
AB  - West Nile (WN) virus transmission in the United States during 2000 was most
      intense on Staten Island, New York, where 10 neurologic illnesses among humans
      and 2 among horses occurred. WN virus was isolated from Aedes vexans, Culex
      pipiens, Cx. salinarius, Ochlerotatus triseriatus, and Psorophora ferox, and WN
      viral RNA was detected in Anopheles punctipennis. An elevated weekly minimum
      infection rate (MIR) for Cx. pipiens and increased dead bird density were present
      for 2 weeks before the first human illness occurred. Increasing mosquito MIRs and
      dead bird densities in an area may be indicators of an increasing risk for human
      infections. A transmission model is proposed involving Cx. pipiens and Cx.
      restuans as the primary enzootic and epizootic vectors among birds, Cx.
      salinarius as the primary bridge vector for humans, and Aedes/Ochlerotatus spp.
      as bridge vectors for equine infection.

PMID- 11589173
TI  - Lipids, lactates, and lacy bones. Sorting out causes and cofactors. 8th
      Conference on Retroviruses and Opportunistic Infections. February 4-8, 2001,
      Chicago. Part Two.

PMID- 11589174
TI  - Developing and approving new drugs for salvage therapy.

PMID- 11589175
TI  - Personal exposure of children to nitrogen dioxide.

PMID- 11589176
TI  - The bones and hormones of deep water divers and pilots of high performance
      aircraft.

PMID- 11589177
TI  - Management of knee osteoarthritis.

PMID- 11589178
TI  - Fenofibrate: a new treatment for hyperuricaemia and gout?

PMID- 11589179
TI  - Effect of leeches therapy (Hirudo medicinalis) in painful osteoarthritis of the
      knee: a pilot study.

PMID- 11589180
TI  - Clinical features of several connective tissue diseases with anti-Golgi antibody.

PMID- 11589181
TI  - Serum procalcitonin measurement for detection of intercurrent infection in
      febrile patients with SLE.

PMID- 11589182
TI  - Effect of daily corticosteroid treatment on CRP response to hip or knee
      replacement in patients with RA.

PMID- 11589183
TI  - Lumbar spondylodiscitis secondary to Enterobacter cloacae septicaemia after
      extracorporeal shock wave lithotripsy.

PMID- 11589184
TI  - Rheumatic pneumonia.

PMID- 11589185
TI  - Referrals to an "early synovitis clinic": are they appropriate?

PMID- 11589186
TI  - Anti-dsDNA antibodies associated with acute EBV infection in Sjogren's syndrome.

PMID- 11589190
TI  - Small bowel biopsies in patients with iron deficiency anaemia.

PMID- 11589191
TI  - Is coeliac disease a confounding factor in the diagnosis of NASH?

PMID- 11589192
TI  - Induction of multiple autoantibodies to islet cell antigens during treatment with
      interferon alpha for chronic hepatitis C.

PMID- 11589193
TI  - ERCP training.

PMID- 11589194
TI  - Reinnervation after childbirth--a new paradigm for sensory bowel symptoms?

PMID- 11589196
TI  - All in the mind.  Fact or artifact?  The placebo effect may be a little of both.

PMID- 11589195
TI  - Managing nutritional care is essential for managing total care.

PMID- 11589197
TI  - [Tamoxifen; wider indications, more frequent controls?].

PMID- 11589198
TI  - Duration of breast feeding and adult arterial distensibility. Humans are
      primates, designed to breast feed for years not months.

PMID- 11589199
TI  - Duration of breast feeding and adult arterial distensibility. Authors did not
      discuss data from prospective studies.

PMID- 11589200
TI  - Duration of breast feeding and adult arterial distensibility. Explanation of
      findings and context before publication might have been helpful.

PMID- 11589201
TI  - Duration of breast feeding and adult arterial distensibility. Dose-response,
      cause and effect relation between breast feeding and heart disease seems
      unlikely.

PMID- 11589202
TI  - Duration of breast feeding and adult arterial distensibility. Statistical
      analysis was unclear.

PMID- 11589203
TI  - Duration of breast feeding and adult arterial distensibility. Does this study
      herald the return of national dried milk?

PMID- 11589204
TI  - Duration of breast feeding and adult arterial distensibility. Breast feeding:
      distension or distortion?

PMID- 11589205
TI  - [The stroke unit: key in the modern management of stroke].

PMID- 11589206
TI  - [Diffusion-weighted magnetic resonance in the diagnosis of brain abscess].

PMID- 11589207
TI  - [Parkinson's disease and convulsions secondary to primary hypoparathyroidism].

PMID- 11589208
TI  - Coping with multiple testing.

PMID- 11589209
TI  - Child-friendly healthcare initiative.

PMID- 11589210
TI  - Possible steroid-induced recurrent patent ductus arteriosus after device closure.

PMID- 11589211
TI  - Systematic review of treatments for infant colic.

PMID- 11589212
TI  - The unnecessary epidemic of folic acid-preventable spina bifida and anencephaly.

PMID- 11589213
TI  - The structure of blood vessels in the germinal matrix and the autoregulation of
      cerebral blood flow in premature infants.

PMID- 11589214
TI  - Immunization status of internationally adopted children.

PMID- 11589215
TI  - End-of-life care.

PMID- 11589216
TI  - Methodologic flaws, wrong answers, and right questions: pediatric office
      emergencies.

PMID- 11589217
TI  - Evidence-based medicine and massage.

PMID- 11589218
TI  - Sedation for electroencephalograms.

PMID- 11589219
TI  - Communication interventions and cancer control: a review of the National Cancer
      Institute's health communication intervention research initiative.
AB  - It is evident, based on the description of the projects and on the preliminary
      reports in this special issue, that this group of studies will help increase
      understanding about how health communication interventions can be used to promote
      cancer prevention and control, as well as to reduce the burden of cancer,
      particularly among those disproportionately affected. The diversity in
      theoretical approaches and intervention modalities used in these studies also
      promises to contribute broadly to understanding of the role of communication in
      health promotion and disease prevention.

PMID- 11589220
TI  - High-density single-nucleotide polymorphism (SNP) map in the 96-kb region
      containing the entire human DiGeorge syndrome critical region 2 (DGCR2) gene at
      22q11.2.
AB  - We constructed a high-density single-nucleotide polymorphism (SNP) map in the 96
      kb region containing the DiGeorge syndrome critical region 2 (DGCR2) gene at
      chromosome 22q11.2, a human counterpart of mouse seizure-related gene SEZ-12. A
      total of 102 SNPs were isolated from the region by systematic screening among 48
      Japanese individuals: 9 SNPs in the 5' flanking region, 3 in the 5' untranslated
      region, 2 in the coding regions, 77 in introns, 7 in the 3' untranslated region,
      and 4 in the 3' flanking region. By a comparison of our data with SNPs deposited
      in the dbSNP database in the National Center for Biotechnology Information, 80
      SNPs (78.4%) were considered to be novel. The ratio of transition to transversion
      was 3.08:1. In addition, eight other types of genetic variations (one GA
      dinucleotide polymorphism and seven insertion/deletion polymorphisms) were
      discovered. The high-resolution map that we constructed will be a useful resource
      for analyzing gene scans of complex diseases mapped to this local segment on
      chromosome 22.

PMID- 11589222
TI  - [Special issue: superbugs viewed from cosmobiology].

PMID- 11589221
TI  - Searching for life on Mars and in meteorites in the 20th century.

PMID- 11589223
TI  - [Superbugs viewed from cosmobiology].
AB  - Superbugs (microorganisms living in unfamiliar and very harsh environments) are
      located in the center of scientific interests in the sense that 1) most of their
      habitats belong to marginal regions of the biosphere, 2) clues for the
      elucidation of the origin of life can be deduced from them, and 3) they are
      deeply correlated to the extraterrestrial life. Not only for the basic scientific
      interests, but also for the applied fields, the spot light is shed to them. We,
      human beings, have been deeply dependent on other organisms through the global
      material flow they make. Microorganisms together with plants are the leading
      characters in this process. Also implicit, our future is surely correlated to
      microorganisms including superbugs. In this special issue, superbugs;
      thermophilic, psychrophilic barophilic etc. are summarized, and future
      development on the study on the superbugs are introduced.

PMID- 11589224
TI  - [Microbes on the edge of global biosphere].
AB  - The search for life on the edge of global biosphere is a frontier to bridge
      conventional bio/ecology and exo/astrobiology. This communication reviews the
      foci of microbiological studies on the inhabitants of the selected "edges", i.e.,
      deep-sea, deep subsurface and Antarctic habitats. The deep-sea is characterized
      as the no-light (non-photosynthetic) habitat, and the primary production is
      mostly due to the chemosynthetic autotrophy at the hydrothermal vents and methane
      rich seeps. Formation of the chemosynthesis-dependent animal communities in the
      deep leads to the idea that such communities may be found in "ocean" of the
      Jovian satellite, Europa. The oxygen minimal layer (OML) in mid-water provides
      another field of deep-sea research. Modern OML is a relatively thin layer, found
      between the water depth of 200 and 1000 m, but was much thicker during the
      periods of oceanic anoxia events (OAEs) in the past. The history of oceanic
      biosphere is regarded as the cycle of OAE and non-OAE periods, and the remnants
      of the past OAEs may be seen in the modem OML. Anoxic (no-O2) condition is also
      characteristic of deep subsurface biosphere. Microorganisms in deep subsurface
      biosphere exploit every available oxidant, or terminal electron acceptor (TEA),
      for anaerobic respiration. Sulfate, nitrate, iron (III) and CO2 are the
      representative TEAs in the deep subsurface. Subsurface of hydrothermal vents, or
      sub-vent biosphere, may house brine (high salt) habitats and halophilic
      microorganisms. Some sub-vent halophiles were phylogenetically closely similar to
      the ones found in the Antarctic habitats which are extremely dry by the
      liophilizing climate. Below the 3000-4000 m-thick glacier on Antarctica, there
      have been >70 lakes with liquid water located. One of such sub-glacial lakes,
      Lake Vostok, has been a target of "life in extreme environments" and is about to
      be drill-penetrated for microbiological studies. These 'microbiological
      platforms' will provide new knowledge about the diversity and potential of the
      Earth's life and facilitate the capability of astrobiologial exploration.

PMID- 11589225
TI  - [Thermophiles and life science in space].
AB  - Thermophiles are microorganisms that can grow at temperatures higher than 50 or
      60 degrees C. There are thermophilic eubacteria and thermophilic archaebacteria.
      Thermophilic microorganisms can be found geothermally and hydrothermally active
      area. The water penetrates into deep subsurface around thermal area and reacts
      with hot basalt. Some of the compounds in the water are reduced by the reaction.
      The water returned to the surface and reacts with seawater or air, depending on
      the location of the thermal area. Many types of autotrophes and heterotrophes
      were found near thermally active area. The microorganisms form the ecosystem
      based on the redox chemical reactions. All of the structural elements in
      thermophilic microorganisms are thermophilic or thermostable. Proteins found in
      microorganisms are thermostable. Though several common characteristics can be
      found in thermostable proteins, it is not easy to attribute the stability to
      specific amino acid residues. DNA in thermophiles is stabilized by increasing the
      G+C content or by histone-like DNA binding proteins. There are several molecular
      biological and geological evidences to support the relation between ancient life
      forms and thermal activity on the Earth. Thermophiles of different life forms may
      be found in thermally active area, in such as those that may be present in
      satellites of Jupiter.

PMID- 11589226
TI  - [Microbial diversity of deep-sea extremophiles--Piezophiles, Hyperthermophiles,
      and subsurface microorganisms].
AB  - Knowledge of our Planet's biosphere has increased tremendously during the last 10
      to 20 years. In the field of Microbiology in particular, scientists have
      discovered novel "extremophiles", microorganisms capable of living in extreme
      environments such as highly acidic or alkaline conditions, at high salt
      concentration, with no oxygen, extreme temperatures (as low as -20 degrees C and
      as high as 300 degrees C), at high concentrations of heavy metals and in high
      pressure environments such as the deep-sea. It is apparent that microorganisms
      can exist in any extreme environment of the Earth, yet already scientists have
      started to look for life on other planets; the so-called "Exobiology" project.
      But as yet we have little knowledge of the deep-sea and subsurface biosphere of
      our own planet. We believe that we should elucidate the Biodiversity of Earth
      more thoroughly before exploring life on other planets, and these attempts would
      provide deeper insight into clarifying the existence of extraterrestrial life. We
      focused on two deep-sea extremophiles in this article; one is "Piezophiles", and
      another is "Hyperthermophiles". Piezophiles are typical microorganisms adapted to
      high-pressure and cold temperature environments, and located in deep-sea bottom.
      Otherwise, hyperthermophiles are living in high temperature environment, and
      located at around the hydrothermal vent systems in deep-sea. They are not typical
      deep-sea microorganisms, but they can grow well at high-pressure condition, just
      like piezophiles. Deming and Baross mentioned that most of the hyperthermophilic
      archaea isolated from deep-sea hydrothermal vents are able to grow under
      conditions of high temperature and pressure, and in most cases their optimal
      pressure for growth was greater than the environmental pressure they were
      isolated from. It is possible that originally their native environment may have
      been deeper than the sea floor and that there had to be a deeper biosphere. This
      implication suggests that the deep-sea hydrothermal vents are the windows to a
      deep subsurface biosphere. A vast array of chemoautotrophic deep-sea animal
      communities have been found to exist in cold seep environments, and most of these
      animals are common with those found in hydrothermal vent environments. Thus, it
      is possible to consider that the cold seeps are also one of slit windows to a
      deep subsurface biosphere. We conclude that the deep-sea extremophiles are very
      closely related into the unseen majority in subsurface biosphere, and the
      subsurface biosphere probably concerns to consider the "exobiology".

PMID- 11589227
TI  - [Psycrophilic organisms in snow and ice].
AB  - Psychrophilic and psycrotrophic organisms are important in global ecology as a
      large proportion of our planet is cold. Two-third of sea-water covering more than
      70% of Earth is cold deep sea water with temperature around 2 degrees C, and more
      than 90% of freshwater is in polar ice-sheets and mountain glaciers. Though
      biological activity in snow and ice had been believed to be extremely limited,
      various specialized biotic communities were recently discovered at glaciers of
      various part of the world. The glacier is relatively simple and closed ecosystem
      with special biotic community containing various psychrophilic and psycrotrophic
      organisms. Since psychrophilic organisms was discovered in the deep ice-core
      recovered from the antarctic ice-sheet and a lake beneath it, snow and ice
      environments in Mars and Europa are attracting a great deal of scientific
      attention as possible extraterrestrial habitats of life. This paper briefly
      reviews the results of the studies on ecology of psychrophilic organisms living
      in snow and ice environments and their physiological and biochemical adaptation
      to low temperature.

PMID- 11589228
TI  - [Biomineralization at hot springs and mineral springs, and their significance in
      relation to the Earth's history].
AB  - Recently, there is strong interest on microbe-mineral interactions. This is
      related also to recent expanded knowledges on extremely severe environments in
      which microbes live. Interaction between microbes and minerals contains
      biomineralization processes. Varieties of biomineralization products are found
      not only in various geologic materials and processes in the earth's history but
      also in present surface environments. Some hot springs represent such
      environments similar to those of unique and extremely severe environments for
      life. In this short review, the author briefly shows some examples of
      biomineralizations at some hot springs and mineral springs, Japan. In such
      environments, iron ore was formed and some varieties of growing stromatolites
      were found. The varieties of stromatolite are siliceous, calcic and manganese
      types. Cyanobacteria and the other bacteria are related to form the stromatolite
      structure. In the Gunma iron ore, sedimentary iron ores were mineralogically
      described in order to evaluate the role of microorganisms and plants in ore
      formation. The iron ore is composed of nanocrystalline goethite. Algal fossils
      are clearly preserved in some ores. Various products of biomineralization are
      found in the present pH 2-3, Fe2(+)- and SO4(2-)-rich streams. Bacterial
      precipitation had variations from amorphous Fe-P-(S) precipitates near the outlet
      of mineral spring, to Fe-P-S precipitates and to Fe-S-(P) precipitates. Mosses
      and green algae are also collecting Fe precipitates in and around the living and
      dead cells. The Gunma Iron Ore can be said as Biologically Induced Iron Ore. At
      Onikobe and Akakura hot springs, growing stromatolites of siliceous and
      calcareous types, were found, respectively. At Onikobe, The stromatolites grow
      especially near the geyser. Cyanobacterial filaments in stromatolite were well
      preserved in the siliceous and calcic stromatolites. The filaments oriented in
      two directions which form the layered structures were found. At Yunokoya hot
      spring, black and brittle stromatolitic structures which were composed of
      amorphous Mn minerals are growing. The form of these structures are
      hemispherical. Many bacteria that were coated with amorphous Mn minerals were
      found on these structures. Furthermore, Precambrian (Proterozoic : Wittenoom
      Chichester region, western Australia) manganese stromatolite was briefly shown in
      comparison. The black stromatolite has been clarified to be composed of
      todorokite. Small spotty and donuts-like shaped todorokite aggregates which are
      very similar to biologically induced Mn-precipitates were found in massive
      dolomite layers.

PMID- 11589229
TI  - Postage stamp poses a Fermi problem.

PMID- 11589230
TI  - A novel mechanism for evolution?

PMID- 11589231
TI  - NIH budget grows, but not R01 success rates.

PMID- 11589232
TI  - 16th-century Algonquian fishermen.

PMID- 11589233
TI  - American Society for Gravitational and Space Biology, Third Annual Meeting,
      October 18-21, 1987, Eccles Conference Center, Utah State University, Logan,
      Utah. Program and abstracts.

PMID- 11589234
TI  - Soviet space flight: the human element.
AB  - Building on past experience and knowledge, the Soviet manned space flight effort
      has become broad, comprehensive, and forward-looking. Their long-running space
      station program has provided the capabilities to investigate long-term effects of
      microgravity on human physiology and behavior and test various countermeasures
      against microgravity-induced physiological deconditioning. Since the beginning of
      Soviet manned space flight, the biomedical training and preparation of cosmonauts
      has evolved from a process that increased human tolerance to space flight
      factors, to a system of interrelated measures to prepare cosmonauts physically
      and psychologically to live and work in space. Currently, the Soviet Union is
      constructing a multimodular space station, the Mir. With the emergence of
      dedicated laboratory modules, the Soviets have begun the transition from small
      scale experimental research to large-scale production activities and specialized
      scientific work in space. In the future, additional laboratory modules will be
      added, including one dedicated to biomedical research, called the "Medilab." The
      longest manned space flight to date (326 days) has been completed by the Soviets.
      The biomedical effects of previous long-duration flights, and perhaps those of
      still greater length, may contribute important insight ito the possibility of
      extended missions beyond Earth, such as a voyage to Mars.

PMID- 11589235
TI  - Program and abstracts. Ninth Annual Meeting, American Society for Gravitational
      and Space Biology. October 20-23, 1993, Hyatt Regency Crystal City, Arlington,
      VA.

PMID- 11589236
TI  - Program and abstracts. Twelfth Annual Meeting of the American Society for
      Gravitational and Space Biology. October 23-26, 1996, Charlotte, NC.

PMID- 11589237
TI  - Program and abstracts. Sixteenth Annual Meeting, American Society for
      Gravitational and Space Biology. Combined meeting with Canadian Space
      Agency/Agence spatiale canadienne and European Low Gravity Research Association.
      October 25-28, 2000, Montreal, QC, Canada.

PMID- 11589238
TI  - Clinostats and centrifuges: their use, value, and limitations in gravitational
      biological research. Report of a symposium held October 19, 1991 in Washington,
      D.C.

PMID- 11589239
TI  - Program and abstracts. Seventh Annual Meeting, American Society for Gravitational
      and Space Biology. October 17-20, 1991, Washington, DC.

PMID- 11589240
TI  - Program and abstracts. Sixth Annual Meeting, American Society for Gravitational
      and Space Biology. November 2-5, 1990, Louisville, Kentucky.

PMID- 11589241
TI  - Gravity and the cell. Report of a conference held December 1-3, 1988 in
      Washington, D.C.

PMID- 11589242
TI  - Psychosocial aspects of obesity and obesity surgery.
AB  - There is a growing consensus that bariatric surgery is the treatment of choice
      for extremely obese individuals who have failed to reduce their weight
      satisfactorily using behavioral or pharmacologic interventions. The gastric
      bypass in particular is associated with excellent long-term weight loss. Although
      most extremely obese individuals will have essentially normal psychological
      functioning, a significant minority suffer from depression, binge eating, trauma,
      or other emotional complications that may require treatment before or after
      bariatric surgery. A structured behavioral assessment, conducted by a mental
      health professional and a registered dietitian, can readily identify those who
      are most likely to require adjunct counseling.

PMID- 11589243
TI  - Medical management of obesity.
AB  - Obesity has become a major health problem in many countries because of its high
      prevalence and causal relationship with serious medical complications. Many of
      the medical complications associated with obesity improve with intentional weight
      in a dose-dependent fashion, and even a modest weight loss of 50% of initial
      weight has beneficial effects. This article reviews the nonsurgical approaches
      for achieving weight loss in obese persons.

PMID- 11589244
TI  - Morbidity of severe obesity.
AB  - Although obesity is an easy diagnosis to make, its etiologies, pathophysiology,
      and symptomatology are extraordinarily complex. Progress in surgical technique
      and anesthesiological management has substantially improved the safety of
      performing operations on the severely obese in the last 20 years. These
      improvements have occurred more or less empirically, without a full understanding
      of etiology or pathophysiology, although this has advanced concomitantly with
      improvements in practice. This review has attempted to provide a framework to
      facilitate progress in the neglected areas of patient selection and choice of
      operation, in an effort to improve long-term outcome. Despite the disparate
      etiologies of obesity and its diverse comorbidities and complications, there are
      unifying interdependent pathogenetic mechanisms of great relevance to the
      practice of antiobesity surgery. The rate of eating, whether driven by HPA
      dysfunction, ambient stress, or related hereditary susceptibility factors
      including the increased energy demands of an expanded body fat mass, participates
      in a cycle that results in disordered satiety (see Fig. 3). This leads to
      substrate overload, causing extensive metabolic abnormalities such as
      atherogenesis, insulin resistance, thrombogenesis, and carcinogenesis. This
      interpretation of the pathophysiology of obesity ironically accords with the
      original meaning of the word obesity: "to overeat." The ultimate solution to the
      problem of obesity--preventing it--will not be forthcoming until the food
      industry is forced to lower production and change its marketing strategies, as
      the liquor and tobacco industries in the United States were compelled to do. This
      cannot occur until the large and fast-growing populations of industrialized
      nations become educated in the personal implications of the energy principle.
      Regardless of whether school curricula are modified to prioritize health
      education, the larger problems of cultural and economic change remain for the
      groups most susceptible to obesity. In this context, antiobesity surgery will
      continue to thrive, especially in the absence of effective alternatives.

PMID- 11589245
TI  - Effects of increased intra-abdominal pressure in severe obesity.
AB  - This article gives an overview, citing animal and clinical studies, of the
      effects of increased intra-abdominal pressure (IAP) in severe obesity. Animal
      studies demonstrate that increased IAP increases pleural pressure, cardiac
      filling pressures, femoral venous pressure, renal venous pressure, systemic blood
      pressure, and vascular resistance, renin and aldosterone levels, and intracranial
      pressure. Thus, the comorbidities presumed secondary to increased IAP in obese
      patients include congestive heart failure, hypoventilation, venous stasis ulcers,
      gastroesophageal reflux, urinary stress incontinence, incisional hernia,
      pseudotumor cerebri, proteinuria, and systemic hypertension.

PMID- 11589246
TI  - Gastric bypass.
AB  - Nearly all morbidly obese patients with satisfactory postoperative weight loss
      experience substantial improvement in the quality of their lives. Improved health
      status is characterized by increased exercise tolerance and improvement or
      resolution of obesity-related comorbidities. Improvement of obesity-related
      medical problems (discussed in the article by Klein elsewhere in this issue) is a
      primary goal of gastric bypass. The patient's ability to interact with others in
      social situations is also enhanced. At present, RYGB may be the only bariatric
      operation that has produced durable long-term weight loss at an acceptable level
      of risk.

PMID- 11589247
TI  - Vertical banded gastroplasty.
AB  - VBG and vertical Silastic ring gastroplasty are simple gastric restriction
      procedures that have defined technical standards. Two recent improvements in the
      operation have been the development of the six-row endolinear cutting-stapling
      instrument that divides the vertical partition without an increase in GI leakage
      and the application of minimally invasive laparoscopic techniques that have
      reduced the incidence of incisional hernia to less than 1%. VBG and vertical
      Silastic ring gastroplasty are procedures that can effectively help select
      patients to manage their morbid obesity. However, these procedures are critically
      dependent on patient compliance. It is not possible to know preoperatively
      whether a candidate will make the lifelong behavior modifications necessary for
      sustained weight loss. Experience has demonstrated that bariatric surgeons have
      limited control over a patient's level of motivation for compliance.

PMID- 11589248
TI  - Malabsorptive obesity surgery.
AB  - Biliopancreatic diversion is the only valuable surgical approach for changing
      intestinal absorption. It is efficient in producing appropriate permanent weight
      loss and has a considerable psychological advantage because it does not impose
      abnormal food restriction. It not only decreases caloric absorption, but it also
      directly improves insulin and lipid metabolism. The ideal technique for the
      construction of BPD is not yet established, but our current preference is for the
      duodenal switch type. BPD must be seen as a means to change an intolerable and
      untreatable disease to a tolerable and treatable one, with substantial
      improvement in quality of life.

PMID- 11589249
TI  - Laparoscopic adjustable silicone gastric banding.
AB  - Laparoscopic adjustable silicone gastric banding (LASGB) is a relatively new
      surgical procedure for the treatment of morbid obesity The most popular banding
      procedure is the vertical banded gastroplasty, however, there are risks involved
      in this procedure, including staple-line disruption and postoperative intractable
      vomiting. This article presents the advantages of using the LASGB device over
      former types of gastric banding.

PMID- 11589250
TI  - Laparoscopic surgery for morbid obesity.
AB  - Minimally invasive approaches to bariatric surgery offer significant advantages
      over those of open surgery. The potential of laparoscopic approaches to reduce
      the morbidity of these operations may exceed that of laparoscopic cholecystecomy
      and laparoscopic Nissen fundoplication because the access incisions for open
      bariatric operations have relatively greater potential for harming the morbidly
      obese patient. Early results of laparoscopic VBG suggest a significant decrease
      in perioperative morbidity compared to the open approach, with similar weight
      loss results. LGB may have the lowest perioperative morbidity and mortality of
      all current bariatric operations. However, the reoperation rate for device
      related complications or failure of the patient to lose sufficient weight appears
      significant. Long-term esophageal motility also remains questionable for the LGB.
      It is hoped that the FDA trial will address many of the issues regarding LGB.
      Results of Lap RYGBP are accumulating and appear promising. The early experience
      suggests that it is technically feasible and safe in the hands of surgeons who
      have appropriate training. It is associated with low perioperative morbidity,
      short hospital stay, and rapid recovery compared to expected results of open
      RYGBP. Weight loss for Lap RYGBP after 5 years is excellent. It is, however, a
      technically formidable operation requiring long operating times and a steep
      learning curve. Early results indicate that technical complications may be
      greater than those experienced with open RYGBP because of the learning curve. Lap
      RYGBP is a promising bariatric procedure with potentially significant advantages
      over open RYGBP. Thus, for patients in the United States, Lap RYGBP may become
      the preferred weight-reduction procedure. The value of hand-assisted bariatric
      procedures and laparoscopic malabsorption procedures must await further study.

PMID- 11589251
TI  - Complications of surgery for obesity.
AB  - Morbidly obese patients are already considered high-risk because of their
      comorbidities. Surgical procedures for obesity are, for the most part, completely
      elective. Careful counseling of the patient before and after the surgery is
      extremely important. This article reviews the general complications of bariatric
      surgery and specific complications of restrictive procedures.

PMID- 11589252
TI  - Rofecoxib: clinical pharmacology and clinical experience.
AB  - BACKGROUND: Rofecoxib is a member of a subgroup of nonsteroidal anti-inflammatory
      drugs (NSAIDs) known as cyclooxygenase-2 (COX-2)-selective inhibitors. It has
      been studied in adult and elderly patients in a number of painful conditions
      (primary dysmenorrhea, acute pain after dental and orthopedic surgery,
      osteoarthritis [OA], and rheumatoid arthritis). OBJECTIVE: This review discusses
      the clinical pharmacology of and clinical experience with rofecoxib, and the role
      of COX-2-selective inhibitors in clinical practice. METHODS: Pertinent studies
      were identified through searches of MEDLINE and EMBASE, as well as the Web sites
      and proceedings of relevant scientific meetings. RESULTS: Although the published
      literature is limited, the data indicate that rofecoxib is an effective analgesic
      agent for the painful conditions in which it has been studied. As a COX-2
      selective inhibitor, rofecoxib offers safety advantages over traditional NSAIDs.
      In clinical trials, gastrointestinal (GI) toxicity, including mucosal damage,
      perforation, ulcers, and bleeding, occurred significantly less often in healthy
      volunteers and patients treated with rofecoxib than in those who received NSAIDs
      such as ibuprofen, naproxen, or diclofenac (all comparisons, P < 0.001). In terms
      of renal toxicity, rofecoxib does not appear to offer a safety advantage over
      traditional NSAIDs. Rofecoxib has not been shown to affect platelets (bleeding
      time and platelet aggregation), unlike traditional NSAIDs. CONCLUSIONS: Rofecoxib
      is an appropriate choice for patients who do not obtain adequate analgesia with
      acetaminophen and those who have not obtained adequate analgesia from, cannot
      tolerate, or are at risk for GI toxicity with traditional NSAIDs. Patients who
      require chronic analgesic medication (ie, those with OA), including those who
      take other medications daily for comorbid conditions, may also benefit from the
      once-daily dosing regimen of rofecoxib.

PMID- 11589253
TI  - A review of the pharmacology and pharmacokinetics of inhaled fluticasone
      propionate and mometasone furoate.
AB  - BACKGROUND: Fluticasone propionate is an established corticosteroid administered
      intranasally for the treatment of rhinitis or by oral inhalation for the
      treatment of asthma. Mometasone furoate, a closely related corticosteroid
      currently available in an intranasal formulation, is being investigated in an
      oral inhalation formulation for the treatment of asthma. OBJECTIVE: This article
      reviews available data on the comparative structure-activity relationships,
      chemistry, pharmacology, pharmacokinetics, and systemic bioavailability of
      fluticasone propionate and mometasone furoate to assess whether claims of
      differences in the absolute systemic bioavailability of the 2 compounds are
      supported by the published literature. METHODS: Information for this review was
      identified through a MEDLINE search of the literature from 1966 to the present
      that contained the term mometasone or fluticasone. The resulting list was
      narrowed by excluding articles dealing with dermatologic applications. A
      systematic review was conducted of the identified literature pertaining to the
      molecular structure, topical potency, lipophilicity, pharmacokinetics, and
      bioavailability of the 2 agents. Additionally, the pharmacology of the 2 moieties
      was assessed by a review of the available literature on receptor binding
      affinity, transactivation and transrepression potency, and inhibition of
      inflammatory-cell cytokine expression. RESULTS: Based on the available data,
      fluticasone propionate and mometasone furoate have similar physicochemical
      properties and structure-activity relationships. When administered intranasally,
      mometasone furoate is reported to have comparable relative systemic
      bioavailability to that of fluticasone propionate (mean plasma area under the
      curve, 123 pmol x h/L vs 112 pmol x h/L, respectively). When administered as a
      single dose by dry powder inhaler, orally inhaled fluticasone propionate is
      reported to have a total systemic bioavailability of approximately 17%, whereas
      that of mometasone furoate is reported to be < 1%. However, the mometasone
      furoate bioavailability study that reported the latter value used lower drug
      doses and a less sensitive assay than the fluticasone propionate bioavailability
      study. When multiple-dose data were used, mometasone furoate had an estimated 11%
      systemic bioavailability, similar to that of fluticasone propionate. CONCLUSIONS:
      Inhaled fluticasone propionate and mometasone furoate appear to have comparable
      potential systemic absorption and, based on the total systemic bioavailabilities
      of the parent compounds, have a low potential for systemic side effects at the
      recommended clinical doses. However, in the case of mometasone furoate, the
      contribution of the active metabolites to systemic effects has not been
      adequately assessed.

PMID- 11589254
TI  - A review of the chemistry, biological action, and clinical applications of
      anabolic-androgenic steroids.
AB  - BACKGROUND: Since its discovery in 1935, numerous derivatives of testosterone
      have been synthesized, with the goals of prolonging its biological activity in
      vivo, producing orally active androgens, and developing products, commonly
      referred to as anabolic-androgenic steroids (AAS), that are more anabolic and
      less androgenic than the parent molecule. OBJECTIVE: This article reviews the
      structure, biotransformation, and mechanism of action of testosterone and some of
      the most commonly used AAS. Clinical applications of the AAS are discussed, and
      guidelines and therapeutic maneuvers for minimizing their side effects are
      outlined. METHODS: Literature for inclusion in this review was identified using
      the libraries of the University of Wisconsin Medical School and School of
      Pharmacy, the author's files, and searches of MEDLINE, Science Citation Index,
      Biological Abstracts, and Chemical Abstracts. RESULTS: The myotrophic action of
      testosterone and its derivatives and their stimulatory effects on the brain have
      led to widespread use of AAS by athletes and "recreational" drug users.
      Consequently, all AAS were classified as class III controlled substances in 1991.
      Nonetheless, AAS have shown benefit in a variety of human disorders, including
      HIV-related muscle wasting and other catabolic conditions such as chronic
      obstructive pulmonary disease, severe burn injuries, and alcoholic hepatitis.
      Because of their diverse biological actions, AAS have been used to treat a
      variety of other conditions, including bone marrow failure syndromes,
      constitutional growth retardation in children, and hereditary angioedema. AAS
      therapy is associated with various side effects that are generally dose related;
      therefore, illicit use of megadoses of AAS for the purpose of bodybuilding and
      enhancement of athletic performance can lead to serious and irreversible organ
      damage. The most common side effects of AAS are some degree of masculinization in
      women and children, behavioral changes (eg, aggression), hepatotoxicity, and
      alteration of blood lipid levels and coagulation factors. CONCLUSIONS: To
      minimize or avoid serious toxicities with AAS therapy, close medical supervision
      and periodic monitoring are important, with dose adjustment as appropriate to
      achieve the minimum effective dose. Given the biological effects and potential
      adverse effects of AAS, administration of these agents should be avoided in
      pregnant women, women with breast cancer or hypercalcemia, men with carcinoma of
      the prostate or breast, and patients with nephrotic syndromes or significant
      liver dysfunction.

PMID- 11589255
TI  - Analysis of trials evaluating combinations of acetylsalicylic acid and
      dipyridamole in the secondary prevention of stroke.
AB  - BACKGROUND: Stroke is one of the leading causes of morbidity and mortality in the
      United States. Patients who suffer a cerebrovascular event are at high risk of a
      recurrence, and secondary prevention is crucial to reducing the burden of
      cerebrovascular disease. Acetylsalicylic acid (ASA, aspirin) is an established
      method of stroke prophylaxis. OBJECTIVE: This review investigates whether the
      addition of dipyridamole to ASA further reduces the risk of stroke recurrence.
      METHODS: To identify clinical trials of the use of combinations of ASA and
      dipyridamole in the prevention of recurrent stroke in patients who have suffered
      a first stroke or transient ischemic attack, the English-language literature was
      searched from 1966 through May 2001 using the MEDLINE, International
      Pharmaceutical Abstracts, EMBASE, and BIOSIS databases. The search terms used
      were dipyridamole, aspirin, acetylsalicylic acid, ischemic stroke, and
      cerebrovascular disorders. CONCLUSIONS: Of the 5 published studies, 3 earlier
      studies detected no differences in outcome when dipyridamole was added to ASA
      therapy for stroke prophylaxis. Two more recent trials found that the addition of
      dipyridamole to ASA therapy provided further reduction in the risk of secondary
      cerebrovascular events compared with placebo and with ASA alone. Further studies
      are needed to confirm long-term benefit.

PMID- 11589256
TI  - Risedronate: a new oral bisphosphonate.
AB  - BACKGROUND: Bisphosphonates have been effective in the treatment of osteoporosis
      and Paget's disease of bone. Risedronate, the newest oral bisphosphonate, is
      approved by the US Food and Drug Administration for the prevention and treatment
      of postmenopausal osteoporosis and glucocorticoid-induced osteoporosis and the
      treatment of Paget's disease of bone. OBJECTIVE: This article reviews current
      studies of risedronate in osteoporosis and Paget's disease of bone and, to the
      extent possible, compares risedronate with other bisphosphonates and other
      therapies. Information on the pharmacokinetics and adverse effects of
      risedronate, and the drug's use in other disorders, is also reviewed. METHODS:
      Clinical studies and review articles concerning the use of risedronate published
      in the English-language literature from 1966 through October 2000 were identified
      through searches of MEDLINE, PREMEDLINE, and International Pharmaceutical
      Abstracts using the search terms risedronate and NE 58095. Recent clinical
      studies, review articles, and consensus statements regarding the use of other
      bisphosphonates were identified through searches of the same databases for this
      period using the search terms bisphosphonates, alendronate, osteoporosis, and
      Paget's disease of bone. RESULTS: The use of risedronate therapy in patients with
      postmenopausal osteoporosis has been shown to increase bone mineral density (BMD)
      and decrease the incidence of fractures compared with placebo. In glucocorticoid
      induced osteoporosis, risedronate has been shown to increase BMD without having a
      consistently significant effect on the risk of fractures. Although there are no
      direct comparisons between bisphosphonates in glucocorticoid-induced
      osteoporosis, risedronate appears to be less effective than alendronate and more
      effective than etidronate in terms of effects on BMD and/or fracture risk. In
      Paget's disease of bone, risedronate has been reported to be more effective than
      etidronate in decreasing serum alkaline phosphatase levels and bone pain.
      Finally, risedronate has been associated with a lower incidence of gastric ulcers
      than alendronate. CONCLUSIONS: In terms of efficacy in the prevention and
      treatment of osteoporosis and the treatment of Paget's disease of bone,
      risedronate is comparable to alendronate, the other orally available
      bisphosphonate. It appears to have better gastrointestinal tolerability than
      alendronate and may be preferred for patients in whom this is a concern. However,
      direct comparative and pharmacoeconomic studies are necessary to determine
      risedronate's relative place in the therapy of osteoporosis and Paget's disease
      of bone.

PMID- 11589257
TI  - Upper gastrointestinal safety evaluation of parecoxib sodium, a new parenteral
      cyclooxygenase-2-specific inhibitor, compared with ketorolac, naproxen, and
      placebo.
AB  - BACKGROUND: Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are
      associated with an increased risk of ulcers and upper gastrointestinal (GI) ulcer
      complications, which has been attributed to the inhibition of cyclooxygenase-1.
      These risks are usually increased in elderly populations. Parecoxib sodium is an
      injectable prodrug of the cyclooxygenase-2-specific inhibitor valdecoxib that has
      exhibited analgesic activity in previous trials. OBJECTIVE: The purpose of this
      study was to compare the GI safety and tolerability profile of parecoxib sodium
      with that of ketorolac, naproxen, and placebo in a 7-day endoscopic trial in
      elderly subjects. METHODS: This was a randomized, double-blind, double-dummy,
      placebo-controlled, parallel-group study. After a normal baseline endoscopy,
      healthy elderly subjects aged 66 to 75 years were randomized to receive i.v.
      parecoxib sodium (10 mg BID), oral naproxen (500 mg BID), or placebo for 7 days,
      or placebo for 2 days followed by i.v. ketorolac (15 mg QID) for 5 days.
      Endoscopy was performed again after 7 days. RESULTS: Among the first 17 subjects
      enrolled, ulcers were observed in all treatment groups except the parecoxib
      sodium group (ketorolac, 4/4 subjects; naproxen, 2/4 subjects; and placebo, 2/5
      subjects). Four subjects in the ketorolac group and 1 subject in the naproxen
      group had multiple gastric ulcers or combined gastric and duodenal ulcers.
      Because of the unexpectedly high incidence of gastroduodenal ulcers observed, the
      study was terminated early and the randomization blind broken. CONCLUSION: These
      findings suggest that elderly patients may be at risk for GI ulceration even
      after short-term use of the conventional NSAIDs ketorolac and naproxen.

PMID- 11589258
TI  - Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination
      capsules for the management of chronic pain: a comparative trial.
AB  - BACKGROUND: Opioid/acetaminophen (APAP) combination analgesics are widely
      prescribed for the relief of moderate pain. Tramadol is a synthetic analgesic
      that has been shown to be effective both alone and in combination with APAP.
      OBJECTIVE: The purpose of this study was to compare the efficacy and tolerability
      of tramadol/APAP tablets with codeine/APAP capsules. METHODS: This 4-week,
      randomized, double-blind, parallel-group, active-control, double-dummy,
      multicenter trial compared tramadol/APAP (37.5 mg/325 mg) with codeine/APAP (30
      mg/300 mg) for the management of chronic nonmalignant low back pain,
      osteoarthritis (OA) pain, or both in adults. Pain relief (scale, 0 = none to 4 =
      complete) and pain intensity (scale, 0 = none to 3 = severe) were measured 30
      minutes and then hourly for 6 hours after the first daily dose each week.
      Patients and investigators assessed the efficacy (scale, 1 = poor to 5 =
      excellent) of each medication, and patients recorded daily doses of study and
      rescue medications. RESULTS: A total of 462 patients (mean age, 57.6 years) were
      randomly assigned to treatment, with 112 (24%) reporting chronic low back pain,
      162 (35%) reporting OA pain, and 188 (41%) reporting both low back and OA pain;
      309 patients (67%) received tramadol/APAP and 153 (33%) received codeine/APAP.
      Pain relief and changes in pain intensity were comparable from day 1, as early as
      30 minutes after the first dose, and lasted for at least 6 hours. Total pain
      relief scores (11.9 for tramadol/APAP; 11.4 for codeine/APAP) and sum of pain
      intensity differences (3.8 for tramadol/APAP; 3.3 for codeine/APAP) were also
      comparable throughout. Overall assessments of efficacy by patients (mean score
      2.9 in each treatment group) and investigators (mean score 3.0 for tramadol/APAP,
      2.9 for codeine/APAP) were similar for the 2 treatment groups. Equivalent mean
      doses (3.5 tablets or capsules daily) and maximum daily doses (5.5 tablets or 5.7
      capsules) were used in the 2 treatment groups. The overall incidence of adverse
      events was comparable, with a significantly higher proportion of patients in the
      codeine/APAP group reporting somnolence (24% [37/153] vs 17% [54/309], P = 0.05)
      or constipation (21% [32/153] vs 11% [35/309], P < 0.01) and a larger proportion
      of patients in the tramadol/APAP group reporting headache (11% [34/309] vs 7%
      [11/153], P = 0.08). CONCLUSION: The results of this study suggest that
      tramadol/APAP tablets (37.5 mg/325 mg) are as effective as codeine/ APAP capsules
      (30 mg/300 mg) in the treatment of chronic nonmalignant low back pain and OA pain
      and are better tolerated.

PMID- 11589259
TI  - Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a double
      blind, randomized, placebo- and active comparator-controlled clinical trial.
AB  - BACKGROUND: In recent studies of acute pain and primary dysmenorrhea, rofecoxib,
      a nonsteroidal anti-inflammatory drug that selectively targets the cyclooxygenase
      2 enzyme, was found to be similar in efficacy to ibuprofen and naproxen sodium.
      OBJECTIVE: The purpose of this study was to determine the analgesic efficacy of a
      single oral dose of rofecoxib 50 mg compared with the combination of codeine 60
      mg/acetaminophen 600 mg in a model of postsurgical dental pain. METHODS: In this
      double-blind, placebo- and active comparator-controlled, parallel-group study,
      patients experiencing moderate or severe pain after the surgical extraction of >
      or = 2 third molars, at least 1 of which was a mandibular impaction, were
      randomized to receive placebo, rofecoxib 50 mg, or codeine 60 mg/acetaminophen
      600 mg. Patient evaluations of pain intensity, pain relief, and global
      assessments were recorded throughout the 24-hour period after dosing. The 2
      stopwatch method was used to determine time to confirmed perceptible pain relief.
      The primary end point assessing overall analgesic effect was total pain relief
      over 6 hours (TOPAR6). Secondary end points were patient global assessment of
      response to therapy (PGART) at 6 hours, onset of analgesia, peak analgesic
      effect, and duration of analgesia. RESULTS: A total of 393 patients were
      enrolled; 182 received rofecoxib, 180 received codeine/acetaminophen, and 31
      received placebo. The overall analgesic effect of rofecoxib 50 mg was greater
      than that of codeine 60 mg/acetaminophen 600 mg for TOPAR6 (12.4 vs 7.0; P <
      0.001) and PGART at 6 hours (P < 0.001). The onset of analgesic effect was
      similar for rofecoxib and codeine/acetaminophen. Peak analgesic effect as
      measured by peak pain relief scores during the first 6 hours was significantly
      greater in the rofecoxib group compared with the codeine/acetaminophen group (P <
      0.001), as was the duration of analgesic effect measured by the time to rescue
      analgesia (9.6 hours vs 2.3 hours, P < 0.001). Adverse events were reported in
      33.0%, 46.1%, and 32.3% of patients treated with rofecoxib,
      codeine/acetaminophen, and placebo, respectively. The most common adverse events
      were nausea (6.0%, 25.0%, and 9.7%, respectively) and vomiting (3.8%, 18.3%, and
      6.5%, respectively). Significantly more patients in the codeine/acetaminophen
      group than in the rofecoxib group experienced adverse events overall (P < 0.050)
      and nausea in particular (P < 0.001). CONCLUSION: In this study of moderate to
      severe postoperative dental pain, the analgesic efficacy of rofecoxib 50 mg was
      greater than that of codeine/acetaminophen, with a lower incidence of adverse
      events and nausea.

PMID- 11589260
TI  - The role of losartan in the management of patients with heart failure.
AB  - BACKGROUND: Heart failure places a burden on patients and health care systems
      worldwide. Although the advent of angiotensin-converting enzyme (ACE) inhibitors
      markedly improved management of this chronic disorder, treatment is still not
      optimal, and morbidity and mortality remain high. OBJECTIVE: This review
      summarizes existing data on losartan, an angiotensin II (AII)-receptor
      antagonist, and compares its potential role with that of ACE inhibitors in the
      management of patients with heart failure. METHODS: Relevant primary studies and
      review articles were identified through a MEDLINE search of the English-language
      literature for the past 5 years and through examination of the reference lists of
      the articles so identified. Search terms included, but were not limited to,
      angiotensin-converting enzyme inhibitors, angiotensin II-receptor antagonists,
      and losartan. RESULTS: Preclinical and clinical studies of losartan have
      demonstrated consistent hemodynamic effects (via selective antagonism of the AII
      type 1 receptor) and a safety profile similar to that of placebo (presumably a
      reflection of the selective approach to AII blockade). In addition, large-scale
      end-point studies have shown losartan to have comparable efficacy to ACE
      inhibitors on a number of morbidity and mortality measures. CONCLUSIONS: There is
      strong evidence for the broad applicability of AII-antagonists in heart failure
      and for the use of AII-antagonists in the treatment of a broader population of
      patients with heart failure, not only those who are unable to tolerate treatment
      with ACE inhibitors.

PMID- 11589261
TI  - A comparison of renal-related adverse drug reactions between rofecoxib and
      celecoxib, based on the World Health Organization/Uppsala Monitoring Centre
      safety database.
AB  - BACKGROUND: Two isoforms of cyclooxygenase (COX) have been identified, both of
      them inhibited by traditional nonsteroidal anti-inflammatory drugs (NSAIDs).
      Inhibition of COX-2 has been associated with the therapeutic effects of NSAIDs,
      whereas inhibition of COX-1 is believed to be the cause of the adverse
      gastrointestinal effects associated with NSAID therapy. When administered at
      therapeutic doses, new COX-2-specific inhibitors inhibit only the COX-2 isoform.
      OBJECTIVE: This study sought to compare renal safety signals between the COX-2
      specific inhibitors rofecoxib and celecoxib, based on spontaneous reports of
      adverse drug reactions (ADRs) in the World Health Organization/Uppsala Monitoring
      Centre (WHO/UMC) safety database through the end of the second quarter 2000.
      METHODS: Disproportionality in the association between a particular drug and
      renal-related ADR was evaluated using a bayesian confidence propagation neural
      network method in which a statistical parameter, the information component (IC)
      value, was calculated for each drug-ADR combination. In this method, an IC value
      significantly greater than 0 implies that the association of a drug-ADR pair is
      stronger than background; the higher the IC value, the more the combination
      stands out from the background. The ratio of actual to expected numbers of ADRs
      was also used to assess disproportionality. RESULTS: As with traditional NSAIDs,
      both COX-2-specific inhibitors were associated with renal-related ADRs. However,
      the adverse renal impact of rofecoxib was significantly greater than that of
      celecoxib. IC values were significantly different for the following comparisons:
      water retention (1.97 rofecoxib vs 1.18 celecoxib; P < 0.01); abnormal renal
      function (2.38 vs 0.70; P < 0.01); renal failure (2.22 vs 1.09; P < 0.01);
      cardiac failure (2.39 vs 0.48; P < 0.01); and hypertension (2.15 vs 1.33; P <
      0.01). In an additional analysis, celecoxib was shown to have a similar renal
      safety profile to that of diclofenac and ibuprofen. CONCLUSIONS: Based on
      spontaneous ADR reports in the WHO/UMC safety database at the end of the second
      quarter 2000, this analysis indicates that rofecoxib has significantly greater
      renal toxicity than celecoxib or traditional NSAIDs. This negative renal impact
      may have the potential to increase the risk for serious cardiac and/or
      cerebrovascular events.

PMID- 11589262
TI  - Cerivastatin versus branded pravastatin in the treatment of primary
      hypercholesterolemia in primary care practice in Canada: a one-year, open-label,
      randomized, comparative study of efficacy, safety, and cost-effectiveness.
AB  - BACKGROUND: Potential cost differences between statins are driven primarily by
      drug costs, differential lowering effects on low-density lipoprotein cholesterol
      (LDL-C) levels, and adverse drug interactions and reactions. OBJECTIVE: The
      purpose of this study was to compare the efficacy, safety, and direct treatment
      costs of cerivastatin and branded pravastatin in adult patients with primary
      hypercholesterolemia over a 1-year period. METHODS: This was a multicenter (48
      sites), randomized, open-label, parallel-group, optional dose-titration study
      conducted in Canada. Patients aged 18 to 75 years with documented primary
      hypercholesterolemia (mean LDL-C > or = 160 mg/dL [> or = 4.5 mmol/L] and at
      least 1 fasting triglyceride measurement < or = 400 mg/dL [< or = 4.5 mmol/L])
      that did not respond adequately to dietary intervention were enrolled. Patients
      who were on a diet at study entry were instructed to continue that diet for the
      duration of the study. Patients not following a diet were also entered into the
      study provided they had received previous dietary counseling and were unwilling
      or unable to comply with this dietary advice. Before randomization, treating
      physicians were required to record a target lipid level for each patient and then
      instructed to randomize patients to treatment with any dose and any titration
      schedule of cerivastatin or branded pravastatin according to their normal
      practice. Physicians were not required to titrate the study drug dose if the
      patient did not achieve the predefined target goal. Lipid analyses were conducted
      at baseline/randomization and at months 3, 6, 9, and 12. All samples drawn for
      lipid analyses were collected after a fast of > or = 10 hours. A cost
      minimization approach was used to compare the direct treatment costs between
      cerivastatin and branded pravastatin. Since the analysis was from the perspective
      of the third-party payer (Ministries of Health), only costs attributed to the
      third-party payer were included. RESULTS: A total of 417 patients were randomized
      to once-daily treatment with cerivastatin 0.1 mg to 0.4 mg (n = 209) or branded
      pravastatin 10 mg to 40 mg (n = 208); 39 (9.4%) of patients discontinued
      prematurely, 19 (4.6%) because of an adverse event. The incidence of adverse
      events was similar for cerivastatin (73.6%) and branded pravastatin (74.9%). The
      majority of adverse events were mild or moderate and included headache, nausea,
      pain, and dizziness. Both cerivastatin and pravastatin were effective in lowering
      LDL-C to target levels (mean reduction 29.8% and 27.5%, respectively, P = 0.35).
      An LDL-C decrease of > or = 20% from baseline to end point was achieved in 74.2%
      of cerivastatin patients and 74.0% of pravastatin patients. The annualized direct
      hyperlipidemia treatment cost was 19% higher in the branded pravastatin group
      compared with the cerivastatin group. A sensitivity analysis designed to examine
      the impact of generic pricing on the cost-minimization analysis indicated that
      the cost difference between cerivastatin and generic pravastatin was not
      significant. CONCLUSIONS: Both cerivastatin and branded pravastatin were well
      tolerated and effective in lowering LDL-C by > or = 20% versus baseline. A cost
      savings in favor of cerivastatin was a reflection of the lower drug acquisition
      cost of cerivastatin compared with branded pravastatin.

PMID- 11589263
TI  - Efficacy and safety of ketoprofen lysine salt mouthwash versus benzydamine
      hydrochloride mouthwash in acute pharyngeal inflammation: a randomized, single
      blind study.
AB  - BACKGROUND: Pharyngodynia, or sore throat, is one of the symptoms most frequently
      reported by patients to primary care physicians. OBJECTIVE: The purpose of this
      study was to compare the efficacy and tolerability of mouthwash formulations of
      ketoprofen lysine salt (KLS), an anti-inflammatory agent, and benzydamine
      hydrochloride (BH), a local anesthetic, in patients with acute inflammation of
      the pharyngeal cavity. METHODS: In this randomized, multicenter, parallel-group,
      single-blind study, patients (who were blinded) were assigned to receive
      undiluted BH 15 mL (22.5 mg) or KLS 10 mL (160 mg) diluted in 100 mL of water.
      Both agents were gargled twice daily until pain remission or up to 7 days. A
      physical examination of the oropharyngeal cavity was performed, and severity of
      edema and hyperemia was assessed after 3 days of treatment and, if symptoms had
      not resolved, after pain remission. RESULTS: Of the 241 patients (120 KLS, 121
      BH), 239 were included in the safety analysis and 232 were in the intent-to-treat
      population. The differences between groups in the duration of analgesic effect
      after the first dose of drug and the time course of pain were found to be
      statistically significant (P = 0.006 and P = 0.017, respectively), favoring KLS.
      Adverse drug-related effects reported included numbness of the tissues in the
      oral cavity, sensation of tingling in the tissues in the oral cavity, dry mouth,
      thirst, and nausea. A significantly greater proportion of BH-treated patients
      reported adverse events (P = 0.001 for all adverse events and drug-related
      adverse events). CONCLUSIONS: KLS mouthwash exerts a significantly longer first
      application analgesic action with significantly greater local tolerability than
      BH in patients with pharyngeal pain of inflammatory and/or infectious origin.

PMID- 11589264
TI  - Acute and chronic effects of brimonidine 0.2% on intraocular pressure and
      pulsatile ocular blood flow in patients with primary open-angle glaucoma: an open
      label, uncontrolled, prospective study.
AB  - BACKGROUND: Brimonidine has been reported to decrease aqueous production and
      increase uveoscleral outflow; however, the hemodynamic effects of brimonidine are
      still under investigation. OBJECTIVE: The purpose of this study was to report the
      acute and chronic effects of brimonidine 0.2% on intraocular pressure (IOP) and
      pulsatile ocular blood flow (pOBF) in patients with primary open-angle glaucoma
      (POAG). METHODS: Nonsmoking patients aged 45 to 67 years with POAG and normal
      blood pressure, heart rate, body mass index, and hemorheologic parameters were
      enrolled in the study. Brimonidine 0.2% was self-administered twice daily for 180
      days. IOP and pOBF were determined using Goldmann applanation tonometry and the
      Langham system. All measurements were taken at baseline and 4, 8, and 12 hours
      after treatment and were repeated on days 7, 15, 30, 60, 90, 120, 150, and 180 of
      treatment. RESULTS: Of the 18 eligible patients, 10 (6 men and 4 women) were
      enrolled (mean age, 51.5 +/- 4.39; range, 47-64 years). When measured 12 hours
      after instillation, mean IOP was significantly reduced by 21.5% (P < 0.001)
      compared with the baseline value. The greatest decrease in IOP (-23.5%) was
      observed at 8 hours. After 12 hours, a significant increase (P < 0.001) in pOBF
      was measured. A stable IOP reduction (P < 0.001 vs baseline), as well as an
      increase in pOBF (P = 0.015), was recorded at the subsequent time points. The
      pOBF increases ranged from 22.5% at day 30 to 9.2% at day 180 of treatment. No
      evidence of adverse events was found at any time point. CONCLUSIONS: In this
      sample of patients with open-angle glaucoma, brimonidine induced a rapid
      reduction in IOP that was significant even after 6 months. Moreover, an increase
      in pOBF was observed from the first day of treatment, and remained consistent
      throughout the study.

PMID- 11589265
TI  - Comparison of the efficacy of formoterol and salmeterol in patients with
      reversible obstructive airway disease: a multicenter, randomized, open-label
      trial.
AB  - BACKGROUND: Beta2-adrenergic agonists are frequently used for the prevention and
      relief of bronchospasm in patients with reversible obstructive airway disease.
      Formoterol and salmeterol are long-acting beta2-agonists. In addition to its long
      duration of action, formoterol has been reported to have an onset of action
      similar to that of albuterol. OBJECTIVE: This study compared the effects on lung
      function of regular twice-daily inhalation of formoterol or salmeterol in adults
      with moderate to moderately severe persistent asthma who were receiving daily
      inhaled corticosteroids. METHODS: In this 6-month, multicenter, open-label,
      parallel-group study, patients with moderate or moderately severe asthma were
      randomized to receive either formoterol 12 microg BID or salmeterol 50 microg
      BID. The primary end point was mean morning peak expiratory flow (PEF) measured 5
      minutes after dosing and entered in a patient diary each day during the first 4
      weeks of treatment. Secondary end points included mean morning and evening
      predose PEF and number of episode-free days recorded in the patient diaries
      during the first 4 weeks of treatment, use and time of rescue medication, symptom
      scores, and overall mean morning predose PEF (spirometric measurements made by
      the physician during scheduled visits) for the entire treatment period. Safety
      assessments included spontaneously reported adverse events and vital signs.
      RESULTS: A total of 528 patients were randomized to study treatment, 262 to
      formoterol and 266 to salmeterol. There were no significant differences in
      demographic or baseline characteristics between treatment groups, except in the
      proportion of current smokers in the formoterol group (4.6%) compared with the
      salmeterol group (1.5%; P = 0.039). Based on the information recorded in
      patients' diaries, those receiving formoterol showed significant improvement in
      mean morning PEF measured 5 minutes after dosing (P < 0.001), reduced use of
      rescue medication (P < 0.03), and an increased number of episode-free days (P <
      0.04) compared with patients receiving salmeterol. Mean predose morning and
      evening PEF and symptom scores based on diary data and mean morning predose PEF
      based on measurements obtained during office visits were comparable between the 2
      treatment groups throughout the study. CONCLUSIONS: In this open-label trial,
      patients randomized to formoterol treatment had greater improvement in mean PEF 5
      minutes after dosing, required significantly less rescue medication (fewer
      actuations of albuterol), and experienced more episode-free days compared with
      patients receiving salmeterol. Thus, although both formoterol and salmeterol are
      long-acting beta2-agonists, formoterol had a more rapid onset of action.

PMID- 11589266
TI  - Factors associated with clinical assessment of overactive bladder and selection
      of treatment.
AB  - BACKGROUND: Overactive bladder (OAB) affects >17 million individuals in the
      United States, but the symptoms of OAB are frequently underreported by patients
      and therefore untreated by physicians. OBJECTIVE: The purpose of this
      observational study was to investigate the demographic and clinical factors
      associated with the decision to treat OAB pharmacologically and identify factors
      associated with physicians' assessment of symptom severity. METHODS: We studied
      31 physicians treating 217 patients with OAB and collected data on patient
      demographic characteristics, OAB symptoms, previous management strategies,
      physicians' assessments of OAB severity, and treatment prescribed. Stepwise
      logistic regression was used to identify factors associated with selecting
      pharmacologic treatment and with physician assessment of severity of OAB
      symptoms. RESULTS: The mean age of the patients was 61.3 years; approximately 82%
      were female, and approximately 73% were white. Participants with urinary
      incontinence were significantly (P < 0.001) more likely to be treated with
      medication than were those with only symptoms of nocturia or urinary frequency.
      Other significant factors associated with pharmacologic treatment were being
      white (odds ratio [OR], 9.5; 95% CI, 2.9-30.8); being black (OR, 5.9; 95% CI, 1.2
      29.7); physician's clinical assessment of OAB as moderate (OR, 3.5; 95% CI, 1.5
      8.2) or severe (OR, 3.8; 95% CI, 1.1-13.7); previous use of medication (OR, 2.9;
      95% CI, 1.1-8.1); and number of incontinence episodes in the last 24 hours (OR,
      1.2; 95% CI, 1.0-1.5). Factors associated with physician assessment of OAB
      severity included distress due to OAB symptoms (OR, 2.1; 95% CI, 1.3-3.2), number
      of incontinence episodes in the last 24 hours (OR, 1.2; 95% CI, 1.1-1.4), and use
      of previous treatment(s) (OR, 0.4; 95% CI, 0.2-0.8). CONCLUSIONS: Both
      demographic and clinical symptoms of OAB were associated with the decision to
      treat OAB with medication, whereas physicians' assessment of OAB severity was
      associated only with clinical symptoms. Urinary incontinence was the key symptom
      associated with the decision to treat patients with medication and with the
      assessment of OAB symptom severity.

PMID- 11589267
TI  - Effect of raloxifene on serum triglycerides in postmenopausal women: influence of
      predisposing factors for hypertriglyceridemia.
AB  - BACKGROUND: Estrogen increases serum triglyceride (TG) levels and induces
      hypertriglyceridemia in susceptible women. The effect of raloxifene (RLX), a
      selective estrogen-receptor modulator, on serum TG has not been studied in
      detail. OBJECTIVE: The purpose of this study was to examine the effect of RLX on
      serum TG levels in postmenopausal women with and without osteoporosis, including
      those with predisposing factors for hypertriglyceridemia. METHODS: Fasting serum
      TG levels were assessed over 36 months in 2738 osteoporotic postmenopausal women
      (mean age, 67 years) assigned to placebo or RLX (60 or 120 mg/d) in an
      osteoporosis treatment trial and over 24 months in 1318 postmenopausal women
      without osteoporosis (mean age, 54 years) assigned to placebo or RLX (60 or 150
      mg/d) in 3 osteoporosis prevention trials. RESULTS: In the osteoporosis treatment
      trial, the median serum TG concentration decreased in all groups, but
      significantly more in the placebo group (placebo, -3.4%; RLX 60 mg/d, -1.4%; RLX
      120 mg/d, -1.3%; P = 0.002). In the osteoporosis prevention trials, the
      percentage change in median serum TG concentration was not significantly
      different among treatments (P = 0.22). Among women with varying degrees of
      hypertriglyceridemia at baseline (>2.82, >3.39, and >4.51 mmol/L), the median
      serum TG level at the end of the study decreased from baseline in all groups,
      with no significant differences among treatments (P > or = 0.13). The effect of
      RLX on serum TG level was not influenced by age, smoking status, use of alcohol,
      or presence of diabetes (P > or = 0.10 for all interactions). Among women in the
      highest tertile of body mass index (>26.4 kg/m2), RLX increased serum TG levels
      significantly compared with placebo (placebo, -3%; RLX 60 mg/d, 6%: RLX 120 mg/d,
      4%; P < 0.05); the absolute increase from baseline with RLX in this subgroup was
      0.05 mmol/L (4.4 mg/dL). CONCLUSIONS: RLX did not increase serum TG in
      postmenopausal women overall or among women with elevated TG levels or evidence
      of diabetes at baseline. TG levels increased slightly but statistically
      significantly in women in the upper tertile of body mass index who were treated
      with RLX.

PMID- 11589268
TI  - Pharmacoeconomics under defined contributions and tiered formularies.

PMID- 11589269
TI  - Methodology for identifying patients at high risk for osteoporotic fracture.
AB  - BACKGROUND: Osteoporotic fractures are associated with significant morbidity,
      mortality, and health care costs. OBJECTIVE: The purpose of this paper is to
      present and validate a mathematical model that managed care organizations can
      apply to administrative claims data to help locate members at risk for
      osteoporotic fracture and estimate future fracture rates. METHODS: Using known
      risk factors from previous clinical studies, 92,000 members of a large Midwest
      health plan were placed in 1 of 4 risk categories based on historical claims
      markers: demographic/lifestyle (age, sex, smoking, alcoholism); steroid use;
      medical history (previous osteoporotic fracture, ordinary bone fracture,
      osteoporosis diagnosis, bone mineral density test); or steroid use with medical
      history. Logistic regression was used to assign a probability of fracture for the
      4 groups over the next 2 years. These predictions were compared with actual
      fracture rates, and refined models were produced. The models were then validated
      by applying them to current data and comparing the predicted fracture rate for
      each group to known results. RESULTS: The model predicted that 1.26% of the study
      members would experience osteoporotic fracture over the next 2 years; the actual
      result was 1.27%. Within the 4 risk groups, the predicted fracture rates were
      lower than the actual rates for the demographic risk group (0.87% predicted vs
      0.97% actual) and higher than the actual rates for the steroid use (1.78%
      predicted vs 1.58% actual), medical history (5.90% predicted vs 4.94% actual),
      and the steroid use with medical history groups (7.80% predicted vs 6.42%
      actual). CONCLUSION: The application of this risk model to an administrative
      claims database successfully identified plan members at risk for osteoporotic
      fracture.

PMID- 11589270
TI  - A comparison of asthma-related expenditures for patients started on montelukast
      versus fluticasone propionate as monotherapy.
AB  - BACKGROUND: The prevalence of asthma is increasing, and this chronic condition
      imposes a substantial economic burden worldwide. It is not known whether newer
      therapies, such as leukotriene receptor antagonists (LTRAs), can ease this
      burden. OBJECTIVE: This analysis examined the association between choice of first
      line asthma control therapy and health care resource utilization and expenditures
      in patients with mild asthma. METHODS: A retrospective cohort analysis of claims
      data for patients who started therapy with fluticasone propionate or montelukast
      between January 1, 1997, and February 28, 1999, was performed, adjusting for
      baseline differences. RESULTS: Data from 343 patients (229 fluticasone; 114
      montelukast) were analyzed. Patients starting therapy with fluticasone were
      significantly older (33.3 vs 27.6 years; P = 0.015) and significantly less likely
      than patients starting therapy with montelukast to have been started on control
      therapy by an asthma specialist (52.0% vs 69.3%; P = 0.007). There were no
      significant differences in mean changes in total asthma-related health care
      expenditures, oral steroid and antibiotic prescriptions, hospitalizations, or
      emergent care visits. The mean increase in total asthma-related pharmacy expenses
      was significantly greater for patients who were prescribed montelukast than for
      those prescribed fluticasone (P < 0.001). Treatment adherence was better in
      patients prescribed montelukast versus fluticasone (5.1 vs 3.1 prescriptions
      filled per year, respectively; P < 0.001). Montelukast patients had a
      significantly lower increase in the number of beta-agonist prescriptions filled
      per year than fluticasone patients (0.19 vs 0.66; P = 0.03). In the subsequent
      year, 4% (10/229) of fluticasone patients added or switched to an LTRA. No
      montelukast patients added to or switched control therapy. CONCLUSION: The mean
      change in total asthma-related health care expenditures was not significantly
      different in patients started on fluticasone propionate versus montelukast.
      Montelukast patients had better adherence to their treatment regimen and required
      fewer beta-agonist prescriptions, which is an indicator of asthma control and
      possibly therapeutic effectiveness.

PMID- 11589271
TI  - Fundamental aspects of chiral separations by capillary electrophoresis.
AB  - A review is presented that surveys the basic theory of direct separation of
      enantiomers by capillary electrophoretic (CE) techniques. These separations are
      based on the formation of diastereomeric complexes between the enantiomeric
      analytes and a chiral selector added to the electrolyte solution. The review
      covers a comprehensive treatment of the equations needed for optimization of
      selectivity coefficients, resolution and analysis time in the zone
      electrophoretic mode. In this context, it takes into account combined equilibria
      of complexation and protonation/deprotonation as well as complexation and
      paritition into micelles. On the basis of these equations, the benefits of
      charged selectors and the optimization potential inherent to pH tuning can be
      documented. In addition, the review deals with some basic aspects of chiral
      isoelectric focusing and briefly discusses indirect enantioseparation. In a
      subsequent section a survey is given on particularfeatures of the various types
      of chiral selectors. Finally, the recent developments in preparative
      enantioseparation in continuous free-flow system and by use of isoelectric
      membranes are discussed.

PMID- 11589272
TI  - Recent developments in chiral capillary electrophoresis and applications of this
      technique to pharmaceutical and biomedical analysis.
AB  - This paper provides an overview of the current status of chiral capillary
      electrophoresis (CE). The emphasis is placed on the application of CE in chiral
      separation of various racemic compounds. During the last two years about 280
      papers, several review articles, and two entire issues, edited by S. Fanali
      (Electrophoresis 1999, 20, 2577-2798, and H. Nishi and S. Terabe (J. Chromatogr.
      A 2000, 879, 1-471.) have been devoted to chiral CE. Enantiomeric separations of
      various compounds, e.g., pharmaceuticals, drug candidates, drugs and related
      metabolites in biological fluids, amino acids, di- and tri peptides, pesticides
      and fungicides, have been performed using different chiral selectors. Native and
      derivatized cyclodextrins continue to be the most widely used chiral selectors.
      Other chiral selectors such as natural and synthetic chiral micelles, crown
      ethers, chiral ligands, proteins, oligo- and polysaccharides, and macrocyclic
      antibiotics have also been applied to chiral CE separations.

PMID- 11589273
TI  - Enantioseparations by capillary electrochromatography.
AB  - The review summarizes recent developments in enantioseparations by capillary
      electrochromatography (CEC). Selected fundamental aspects of CEC are discussed in
      order to stress those features which may allow the success of this technique in
      the competitive field of enantioseparations. In addition, the comparative
      characteristics of the different modes of chiral CEC and the stationary phases
      are presented. The effects of the characteristics of the stationary and liquid
      phases and operational conditions on the separation results are discussed.
      Finally, some future trends are briefly addressed.

PMID- 11589274
TI  - Heptakis(2-O-methyl-3,6-di-O-sulfo)-beta-cyclodextrin: a single isomer, 14
      sulfated beta-cyclodextrin for use as a chiral resolving agent in capillary
      electrophoresis.
AB  - The first single-isomer, 14-sulfated beta-cyclodextrin, the sodium salt of
      heptakis(2-O-methyl-3,6-di-O-sulfo)-beta-cyclodextrin (HMdiSu) has been used to
      separate 24 pharmaceutical weak base enantiomers in pH 2.5 background
      electrolytes using capillary electrophoresis. For the weakly binding bases, the
      cationic effective mobilities decreased, approached zero, and then increased
      again. For the strongly binding bases, the cationic effective mobilities
      decreased, became anionic at very low concentrations of HMdiSu, passed an anionic
      mobility maximum, then decreased again as the HMdiSu concentration was increased.
      Viscosity corrections according to Walden's rule did not eliminate these
      unexpected effective mobility extrema. The mobility extrema were rationalized by
      extending the charged resolving agent migration model (CHARM model) to include
      ionic strength effects.

PMID- 11589275
TI  - pH-dependence of complexion constants and complex mobility in capillary
      electrophoresis separations of dipeptide enantiomers.
AB  - The chiral separation of the LL- and DD-enantiomers of the dipeptides Ala-Tyr,
      Phe-Phe, and Asp-PheOMe has been investigated at pH 2.5 and pH 3.5 using beta
      cyclodextrin (beta-CD), heptakis-(2,6-di-O-methyl)-beta-cyclodextrin, and
      heptakis-(2,3,6-tri-O-methyl)-beta-cyclodextrin as chiral selectors. According to
      electrospray mass spectrometry, heptakis-(2,6-di-O-methyl)-beta-cyclodextrin was
      a mixture of six isomers. Reversal of the enantiomer migration order upon
      increasing the buffer pH from 2.5 to 3.5 was observed for all peptides with beta
      cyclodextrin, for Ala-Tyr and Phe-Phe in the presence of heptakis-(2,3,6-tri-O
      methyl)-beta-cyclodextrin, and for Ala-Tyr using heptakis-(2,6-di-O-methyl)-beta
      cyclodextrin. The migration behavior could be explained on the basis of the
      complexation constants and the mobilities of the peptide-cyclodextrin complexes.
      Both, the binding constants and complex mobilities decreased with increasing pH
      as the overall-charge of the peptides decreased. While the complexation constants
      primarily determined the migration order at pH 2.5, complex mobility dominated in
      most cases at pH 3.5.

PMID- 11589276
TI  - Enantiomeric separation of hydroxy acids and carboxylic acids by diamino-beta
      cyclodextrins (AB,AC,AD) in capillary electrophoresis.
AB  - Selectively modified 6,6'-dideoxy-6,6'-L-diamino-beta-cyclodextrins (AB, AC, AD)
      were successfully used as chiral selectors for the enantiomeric separation of
      hydroxy acids and carboxylic acids (in particular, phenoxyalkanoic acid
      herbicides) in capillary electrophoresis (CE). Chiral separations were obtained
      at a low selector concentration (1 mM) with good enantioselectivity and
      resolution factors. Separations were optimized as a function of pH. The different
      position of the charged groups on the upper rim greatly influenced the
      separation, accounting for electrostatic interactions between the protonated
      amino groups of the cyclodextrins (CDs) and the carboxylate of the selectands.
      The best enantiomeric separation of hydroxy acids was obtained with the AC
      regioisomer, whereas carboxylic acids were well resolved only by the AB
      regioisomer. A recognition model is proposed, based on two-dimensional nuclear
      magnetic resonance (2-D NMR) experiments, in which the orientation of the guest
      in the inclusion complex is determined by the electrostatic interactions between
      the selectand and the CD upper rim.

PMID- 11589277
TI  - Mechanistic study on the opposite migration order of clenbuterol enantiomers in
      capillary electrophoresis with beta-cyclodextrin and single-isomer heptakis(2,3
      diacetyl-6-sulfo)-beta-cyclodextrin.
AB  - Opposite migration order was observed for the enantiomers of the chiral beta2
      adrenergic drug clenbuterol (CL) in capillary electrophoresis (CE) when resolved
      with native beta-cyclodextrin (beta-CD) and heptakis (2,3-diacetyl-6-sulfo)-beta
      CD (HDAS-beta-CD). The possible mechanisms of the affinity reversal of the CL
      enantiomers depending on the structure of the CD were studied using 1H-nuclear
      magnetic resonance (1H-NMR) spectrometry and one-dimensional rotating frame
      nuclear Overhauser and exchange spectrometry (1-D ROESY). Significant differences
      were observed between the structure of the (+/-)-CL complexes with beta-CD and
      HDAS-beta-CD.

PMID- 11589278
TI  - Determination of the enantiomerization barrier of thalidomide by dynamic
      capillary electrokinetic chromatography.
AB  - Enantioselective chromatographic methods, representing the most commonly used
      techniques for the determination of enantiomeric ratios, can also be used for the
      evaluation of stereochemical integrity. In the present study, dynamic capillary
      electrokinetic chromatography (DEKC) was employed to determine the
      enantiomerization barrier of thalidomide. In the presence of the chiral mobile
      phase additive carboxymethyl-beta-cyclodextrin, the interconverting enantiomers
      of thalidomide produced characteristic elution profiles exhibiting plateaus
      and/or peak broadening between 25 and 55 degrees C at pH 8. To obtain the
      enantiomerization barrier of thalidomide from experimental data, the fast and
      efficient simulation program ChromWin was used to simulate the experimental
      interconversion profiles and to obtain the apparent rate constants k1app(T).
      Additionally, these values were compared with the novel approximation function
      for the direct calculation of enantiomerization barriers from chromatographic
      parameters of elution profiles. From the rate constants k1app(T) of temperature
      dependent measurements the kinetic activation parameters deltaG(T)#,deltaH#, and
      deltaS# of the enantiomerization of thalidomide were obtained. At 25 degrees C,
      the enantiomerization barrier deltaG# was determined to be 102 +/- 1 kJ/mol at pH
      8 in the dynamic electrokinetic chromatographic experiment.

PMID- 11589279
TI  - Fast enantiomeric separation of basis drugs by electrokinetic chromatography.
      Application to the quantitation of terbutaline in a pharmaceutical preparation.
AB  - Electrokinetic chromatography (EKC) using micelles of bile salts alone or mixed
      with sodium dodecyl sulfate (SDS) and neutral, anionic, or cationic cyclodextrins
      (CDs) in the separation buffer has been employed in order to achieve fast
      enantiomeric separation of basic drugs. A study of the enantiomeric separation
      ability of these chiral selectors concerning four basic drugs (epinephrine,
      terbutaline, clenbuterol, and salbutamol) has been carried out under different
      experimental conditions. The best chiral selectors to perform the enantiomeric
      separation of these drugs were neutral beta-CD derivatives, specifically
      permethylated beta-CD PM-beta-CD. The effect of the PM-beta-CD concentration,
      temperature, and applied voltage on the enantiomeric resolution of the basic
      drugs was investigated. The use of a 25 mM ammonium acetate buffer (pH 5.0), 30
      mM in PM-beta-CD together with an applied voltage of 20 kV and a temperature of
      15 degrees C enabled the individual and fast enantiomeric separation of
      epinephrine, norepinephrine, terbutaline, clenbuterol, and salbutamol each one
      into its two enantiomers in less than 3 min. The EKC method was validated
      (precision and accuracy) to quantitate terbutaline in a pharmaceutical
      preparation, obtaining a limit of detection of 4 microg/mL.

PMID- 11589280
TI  - Chiral separation of pharmacologically active dihydropyrimidinones with
      carboxymethyl-beta-cyclodextrin.
AB  - We report on the chiral separation of pharmacologically active
      dihydropyrimidinones by capillary electrophoresis (CE) using carboxymethyl-beta
      cyclodextrin as chiral selector. The influence of selector concentration, pH, and
      the addition of varying amounts of methanol is investigated. Out of 21 compounds
      investigated, 19 were resolved, 13 with baseline separation.

PMID- 11589281
TI  - Rapid screening for chiral separations by short-end injection capillary
      electrophoresis using highly sulfated cyclodextrins as chiral selectors.
AB  - Two series of amino acid derivatives and phenylamines were used to evaluate the
      potential of highly sulfated cyclodextrins (HS-CDs) for the screening for chiral
      separations by capillary electrophoresis (CE). HS-CDs showed to be very versatile
      and to exhibit very high enantioselectivity. The use of short-end injection
      allowed to reduce dramatically the analysis time. From the results obtained, a
      scheme for the rapid screening of enantiomeric molecules was developed and
      applied to various chiral drugs. Results are very satisfying as almost all
      compounds (62 out of 67) could be baseline-resolved. Usually, less than three
      experiments were necessary to obtain very good separation.

PMID- 11589282
TI  - Enantiomeric separation of chiral phenoxy acid herbicides by electrokinetic
      chromatography. Application to the determination of analyte-selector apparent
      binding constants for enantiomers.
AB  - The enantiomeric resolution of chiral phenoxy acid herbicides was performed by
      electrokinetic chromatography using a cyclodextrin as chiral pseudophase (CD
      EKC). A systematic evaluation of several neutral and charged cyclodextrins was
      made. Among the cyclodextrins tested, (2-hydroxy)propyl beta-cyclodextrin (HP
      beta-CD) was found to be the most appropriate for the enantioseparation of
      phenoxy acids. The influence of some experimental conditions, such as nature and
      pH of the background electrolyte, chiral selector concentration, and temperature,
      on the enantiomeric separation of phenoxy acids was also studied. The use of a 50
      mM electrolyte solution in ammonium formate at pH 5 and a temperature of 40
      degrees C enabled the enantiomeric resolution of four of the six phenoxy acids
      investigated (2-phenoxypropionic acid, 2(3-chlorophenoxy)propionic acid, 2-(4
      chlorophenoxy)propionic acid, and 2-(2,4-dichlorophenoxy)propionic acid)
      obtaining migration times ranging from 9 to 15 min. Mixtures of the two phenoxy
      acids not enantiomerically resolved (2-(4-chlorophenoxy)-2-methylpropionic acid
      and 2-(2,4,5-trichlorophenoxy)propionic acid) and up to three of the phenoxy
      acids enantiomerically resolved were separated in about 15 min. Finally, the
      apparent binding constants for each enantiomer-HP-beta-CD pair were calculated at
      two temperature values (20 and 40 degrees C).

PMID- 11589283
TI  - Separation of ritalin racemate and its by-product racemates by capillary
      electrophoresis.
AB  - Ritalin, [(+)-threo]methylphenidate hydrochloride, is a chiral drug substance
      with two chiral centers. The drug substance may contain three pairs of
      enantiomers, [(+)-threo], [(-)-threo], [(+)-erythro] and [(-)-erythro] isomers,
      and its degradation products, threoritalinic acid racemate. Determination of the
      optical purity of ritalin drug substance and the amount of its by-product isomers
      is a critical step in the single-isomer drug development. In order to efficiently
      recognize the three pairs of enantiomers by one method, capillary electrophoresis
      (CE) was employed for the separation. The three pairs of enantiomers in CE showed
      different enantioselectivities with eight different types of CDs. Only 2,6-di-o
      methyl-beta-cyclodextrin (DM-beta-CD) and carboxymethyl-beta-cyclodextrin (CM
      beta-CD) showed enantioselectivity to all these pairs of enantiomers. With
      respect to separation resolution and efficiency, DM-beta-CD was chosen as the
      chiral selector. For optimization of the separation conditions, the concentration
      of DM-beta-CD, pH of the buffer solution, and temperature of the capillary were
      further studied.

PMID- 11589284
TI  - Chiral separation of pyrethroic acids with single isomer permethyl monoamino beta
      cyclodextrin selector.
AB  - Enantiomers and diastereomers of chrysanthemic, permethrinic, and deltamethrinic
      pyrethroic acids were separated from each other, using positively ionizable
      permethyl monoamino beta-cyclodextrin (PMMAbetaCD). The highest chiral resolution
      value was 20.0. The optimum conditions of separation were found to be 16 mM
      PMMAbetaCD concentration and pH 6.5, where analytes and selector were in
      oppositely ionized states. Selectivity of PMMAbetaCD proved to be the best among
      the cyclodextrin derivatives studied.

PMID- 11589285
TI  - Enantioseparation of chiral thiobarbiturates using cyclodextrin-modified
      capillary electrophoresis.
AB  - The racemates of several chiral thiobarbiturates were separated by using
      different cyclodextrins in capillary electrophoresis (CE). Six neutral and
      negatively charged cyclodextrins 1 (CDs) were employed as chiral separators
      whereof five led to successful separation of enantiomeric thiobarbiturate pairs.
      The CDs used were the native alpha-CD, beta-CD, gamma-CD, and heptakis-(2,6-di-O
      methyl)-beta-cyclodextrin (HDM) as well as heptakis-(2,3-di-O-methyl-6-sulfato)
      beta-cyclodextrin (HDMS) and heptakis-(2,3-di-O-acetyl-6-sulfato)-beta-CD (HDAS).
      Five of the six chiral thiobarbiturates studied could be resolved at a basic pH
      value of 9.4 and a phosphate buffer concentration of 100 mM in a fused-silica
      capillary. Structurally related substances showed a similar behavior in
      separation: 1 and 2 bearing the center of chirality in the side chain at C5 can
      be best separated using gamma-CD, the N-alkyl-substituted compounds 3 and 4 as
      well as the N/S-dialkyl-substituted compound 5 could be resolved with HDM. Using
      the neutral CDs, the migration times were relatively small (< 11 min). 3 and 4
      could be also resolved by means of the negatively charged HDMS. In the latter
      case, the migration time is twice as long as with HDM.

PMID- 11589286
TI  - Evidences of cyclodextrin-mediated enantioselective photodegradation of rac
      nicardipine by capillary electrophoresis.
AB  - Capillary electrophoresis (CE) was applied to photostability studies on rac
      nicardipine, a dihydropyridine chiral drug. CE methods were developed able to
      provide the enantioresolution of drug and its separation from the
      photodegradation products. Enantioresolution was achieved using 5% sulfated-beta
      cyclodextrin (S-beta-CD) as chiral selector in 20 mM triethanolammonium phosphate
      solution (pH 3). The photostability studies were carried out on inclusion
      complexes of rac-nicardipine with beta-cyclodextrin (beta-CD) and (2
      hydroxypropyl)-beta-cyclodextrin (HP-beta-CD) in aqueous solutions (pH 7.4 and
      5). The CE analysis of the solutions exposed to UV-A and UV-B radiations showed a
      photoprotective effect by beta-CD; conversely, HP-beta-CD proved to favor the
      drug photodegradation. Moreover, evidences for CDs-mediated stereoselective
      photodegradation of rac-nicardipine were obtained. In fact, two distinct
      photodegradation profiles were observed for the nicardipine enantiomers in the
      presence of the CDs. The photodegradation was found to follow an apparent first
      order kinetics and two different kinetic constants (k) were obtained for the two
      enantiomers. After exposure to UV-A and UV-B radiations, the solutions contained
      residual nicardipine with a significant change in the enantiomeric ratio; this
      effect was depending on the CD used for the inclusion complexation.

PMID- 11589287
TI  - Separation of basic drug enantiomers by capillary electrophoresis using
      ovoglycoprotein as a chiral selector: comparison of chiral resolution ability of
      ovoglycoprotein and completely deglycosylated ovoglycoprotein.
AB  - Separations of basic drug enantiomers by capillary electrophoresis (CE) using
      ovoglycoprotein (OGCHI) as a chiral selector are described. The effects of
      running buffer pH and 2-propanol content on the migration times and resolution of
      basic drug enantiomers were examined using a linear polyacrylamide-coated
      capillary. High resolution of basic drug enantiomers was attained using a mixture
      of 50 mM sodium phosphate buffer (pH 4.5-6.0) and 2-propanol (5-30%) including 50
      microM OGCHI. It was found that ionic and hydrophobic interactions could work for
      the recognition of basic drug enantiomers. Further, we compared the chiral
      resolution ability of OGCHI with that of completely deglycosylated OGCHI (cd
      OGCHI) using them as chiral selectors in CE. OGCHI showed higher resolution for
      basic drug enantiomers tested than cd-OGCHI. The results suggest that the chiral
      recognition site(s) for OGCHI exists on the protein domain of OGCHI.

PMID- 11589288
TI  - Capillary electrophoresis investigation on the structure-enantioselectivity
      relationship in synthetic cyclopeptides as chiral selectors.
AB  - We recently reported the use of a deconvolution strategy to identify the best
      chiral selectors for Nalpha-2,4-dinitrophenyl (Dnp) amino acid racemates from a
      combinatorial library composed of thousands of homodetic cyclohexapeptides.
      Selection was based on the capillary electrophoresis (CE) enantioresolution for a
      set of Dnp-amino acids. The groups involved in the chiral discrimination were
      assessed by nuclear magnetic resonance (NMR) spectroscopy, which revealed a
      strong involvement of one of the aromatic rings of the cyclopeptide in the
      binding with the analyte. In order to better understand the recognition
      mechanism, and thus extend the applicability of the analytical system,
      modifications on both analyte and selector structure were introduced. The effects
      on separation were evaluated in terms of resolution values and mobility
      variation.

PMID- 11589289
TI  - Enantioselective analysis of albendazole sulfoxide in cerebrospinal fluid by
      capillary electrophoresis.
AB  - Albendazole (ABZ) is a benzimidazole anthelmintic drug used in the treatment of
      neurocysticercosis. After oral administration, ABZ is rapidly oxidized to
      albendazole sulfoxide (ABZSO), which has an asymmetric sulfur center, and later
      to albendazole sulfone (ABZSO2). ABZSO is the active metabolite responsible for
      the therapeutic effect of the drug. Previous studies have demonstrated
      pharmacokinetic differences between the two enantiomers, with the predominance of
      (+)-ABZSO in human biological fluids. This article describes for the first time
      the enantioselective analysis of ABZSO in cerebrospinal fluid (CSF) using
      capillary electrophoresis. The samples were prepared by liquid-liquid extraction
      using chloroform:isopropanol (8:2 v/v). The resolution of ABZSO enantiomers was
      obtained with a fused-silica capillary (60 cm x 75 microm ID) using 20 mmol/L
      Tris, pH 7.0, with 3.0% w/w sulfated beta-cyclodextrin as running buffer. The
      coefficient of variations and % relative error obtained for both within-day and
      between-days assays were lower than 15%. The method was linear over the
      concentration range of 100 to 2,500 ng/mL for each enantiomer, indicating that it
      is suitable for the analysis of ABZSO enantiomers in CSF from patients medicated
      with ABZ.

PMID- 11589290
TI  - Enantiomeric analysis of the five major monohydroxylated metabolites of
      methaqualone in human urine by chiral capillary electrophoresis.
AB  - Methaqualone (MQ; 2-methyl-3-o-tolylquinazolin-4(3H)-one) is a hypnotic and
      anticonvulsive drug in which the rotation about the nitrogen-to-aryl bond between
      the planar 2-methyl-quinazolin-4(3H)-one structure and the o-tolyl moiety is
      sterically hindered at body temperature. MQ and its five major monohydroxylated
      metabolites found in urine, 4'-hydroxymethaqualone (4'OH-MQ), 2'
      hydroxymethaqualone (2'-OH-MQ), 3'-hydroxymethaqualone (3'OH-MQ), 2
      hydroxymethaqualone (2OH-MQ) and 6-hydroxymethaqualone (6OH-MQ), are thus chiral
      substances whose enantiomers are shown to be separable by chiral capillary
      electrophoresis at pH 2.1 in the presence of 50 mM (2-hydroxypropyl)-beta
      cyclodextrin (OHP-beta-CD). Other neutral derivatives of beta-CD, namely (2
      hydroxypropyl)-gamma-CD, (2,3,6-trimethyl)-beta-CD, and (2,6-di-O-methyl)-beta-CD
      were found to be able to resolve the enantiomers of some but not all of these six
      components. With OHP-beta-CD, simultaneous analysis of the enantiomers of MQ and
      its five metabolites is hampered by the difficulty in separating MQ and 4'OH-MQ,
      the major urinary metabolite. A two-step solid phase extraction process is shown
      to permit discrimination between these two compounds and thus analysis of MQ
      enantiomers in unhydrolyzed urines that were collected overnight after
      administration of 250 mg of racemic MQ. Furthermore, analysis of liquid/liquid or
      solid-phase extracts of enzymatically hydrolyzed urines reveals the distribution
      of the enantiomers of the five hydroxymetabolites of MQ and, for the first time,
      insight into the stereoselectivity of the MQ metabolism. The major metabolite,
      4'OH-MQ, is shown to be excreted almost exclusively as single enantiomer. The two
      urinary enantiomers of 6OH-MQ are present at about equal amounts, whereas unequal
      amounts are noted for the enantiomers of 3'OH-MQ, 2OH-MQ, and 2'OH-MQ.

PMID- 11589291
TI  - Enantioseparation of the anticoagulant drug phenprocoumon in capillary
      electrophoresis with UV and laser-induced  fluorescence detection and application
      of the method to urine samples.
AB  - The enantioseparation of phenprocoumon (PhC) in capillary electrophoresis (CE)
      has been studied using various cyclodextrins (CDs) such as native alpha, beta and
      gamma-CD and several neutral and randomly, as well as selectively substituted
      charged CD derivatives. Reversal of the enantiomer migration order was observed
      when using heptakis(2,3,6-tri-O-methyl (TM)-beta-CD as a chiral selector compared
      to all other CDs used. The detection of PhC was performed using either UV or
      laser-induced fluorescence (LIF) detection. The limit of detection (LOD) observed
      with LIF detection was ca. 20 times lower compared to UV. The method has been
      applied to the analysis of urine samples of the patient under treatment with PhC
      in combination with other drugs such as ramipril, hydrochlorothiazide, and
      nifedipine.

PMID- 11589292
TI  - Direct chiral resolution of malic acid in apple juice by ligand-exchange
      capillary electrophoresis using copper(II)-L-tartaric acid as a chiral selector.
AB  - Chiral resolution of native DL-malic acid was achieved by ligand-exchange
      capillary electrophoresis using copper(II)-L-tartrate as a chiral selector.
      Factors affecting chiral resolution, migration time, and peak area of malic acid
      were studied. The running conditions for optimum separation of malic acid were
      found to be 1 mM copper(II) sulfate-1 mM L-tartrate (pH 5.1) with an effective
      voltage of -20 kV at 30 degrees C, using direct detection at 280 nm, and
      resolution (Rs) of racemic malic acid was approximately 4. With this system, D-
      and L-malic acids in apple juice were analyzed successfully.

PMID- 11589293
TI  - Chiral separation of amino acid esters by micellar electrokinetic chromatography.
AB  - Micellar electrokinetic chromatography (MEKC) was used for the chiral separation
      of uncharged analytes (C- and N-protected amino acids). Sodium dodecyl sulfate
      (SDS) was the micelle forming agent, and different cyclodextrin (CD) derivatives
      were added as chiral selectors. Suitable conditions for the enantioseparation
      were found by variation of the separation conditions. The influence of addition
      of organic solvents like acetonitrile or methanol, and other chiral additives
      (camphor-10-sulfonic acid, malic acid) was examined. The addition of an organic
      modifier resulted in different effects on micelle formation, and thereby on the
      separation. The used chiral additives did not improve the selectivity.
      Furthermore, dependence of the electroosmotic flow (EOF), and the capacity
      factors on the concentration of CDs was investigated. Increasing the CD
      concentration, both the EOF to a smaller extent as well as the capacity factors
      decrease. Nevertheless, the enantioseparation is improved with a CD-concentration
      up to 30 mM. Higher CD-concentrations reduce the separation of the analytes.

PMID- 11589294
TI  - Development of stereoselective nonaqueous capillary electrophoresis system for
      the resolution of cationic and amphoteric analytes.
AB  - A stereoselective ion-pair nonaqueous capillary electrophoresis (NACE) method
      employing the partial filling technique with N-derivatized amino acids, e.g., (R)
      and (S)-3,5-dinitrobenzoyl-leucine (DNB-Leu), as chiral selector for the
      separation of "pseudoenantiomeric" cinchona alkaloid derivatives and other
      structurally related basic compounds like the enantiomers of mefloquine is
      presented. Originating from NACE with cinchona alkaloid derivatives as chiral
      counterions, this method was developed by application of the reciprocity
      principle of chiral recognition, which was proven to be valid for stereoselective
      ion-pair capillary electrophoresis (CE). A variety of basic and amphoteric
      selectands (SAs) could be well resolved. Thereby, the separation was primarily
      based on stereoselective ion-pair formation of corresponding SA stereoisomers and
      mobility differences of free and complexed (ion-paired) SAs. Additionally, in the
      case of diastereomeric SAs, naturally existing mobility differences between the
      diastereomers played also a role, but was shown by control experiments with
      racemic DNB-Leu and without selector (SO) to be of minor contribution to overall
      separation selectivity. Due to its simplicity, speed, and good reproducibility,
      the established method can be utilized for fast screening of cationic as well as
      amphoteric chiral compounds, and therefore is a valuable tool in the development
      of new chiral selectors and chiral stationary phases. Small sample amounts of the
      SO (4-5 mg) and only analytical amounts of SAs are needed, and about 20-50
      compounds per day can be tested.

PMID- 11589295
TI  - On-line capillary electrophoresis-electrospray mass spectrometry for the
      stereoselective analysis of drugs and metabolites.
AB  - The on-line combination of partial-filling capillary electrophoresis and
      electrospray ionization mass spectrometry was demonstrated for the
      enantioseparation of pharmaceutical drugs and metabolites, namely amphetamines,
      methadone, venlafaxine and selected tropane alkaloids. The partial-filling
      technique proved to be a suitable and efficient approach to avoid mass
      spectrometry (MS) source contamination, as well as signal suppression due to
      nonvolatile additives. To achieve chiral separation, various chiral selectors
      were applied, including neutral and particularly negatively charged
      cyclodextrins. Because of the countercurrent contribution, charged cyclodextrins
      were found more suitable for the on-line MS detection of separated enantiomers.
      Hyphenation of capillary electrophoresis (CE) with mass spectrometry was found
      appropriate for the stereoselective analysis of methadone in real serum samples.
      Moreover, the use of MS in the selected ion monitoring mode resulted in a very
      high selectivity, as well as improved sensitivity compared to UV detection.
      Finally, with atropine as a model compound, the quantitative performances of the
      method were evaluated and showed high sensitivity, as well as good repeatability
      in terms of migration time and peak area ratio.

PMID- 11589296
TI  - Experimental designs to investigate capillary electrophoresis-electrospray
      ionization-mass spectrometry enantioseparation with the partial-filling
      technique.
AB  - An experimental design approach is described to evaluate the main electrophoretic
      parameters involved in the enantioseparation of pharmaceuticals by capillary
      electrophoresis (CE) coupled to electrospray ionization-mass spectrometry (ESI
      MS). For all experiments, the partial-filling technique was applied to avoid the
      chiral selector entering in the mass spectrometer ion source with a negative
      effect on the electrospray performance. To carry out enantioseparation, a
      volatile buffer constituted of 20 mM ammonium acetate at pH 4.0, and a polyvinyl
      alcohol-coated capillary were used. Methadone was employed as the model compound
      and three different cyclodextrins (CDs), namely sulfobutyl ether-beta-CD,
      carboxymethylated-beta-CD and hydroxypropyl-beta-CD, were selected in order to
      study the countercurrent process. Two different experimental designs were chosen:
      (i) a full-factorial design to examine the effects and significance of the
      investigated factors, and (ii) a central composite face-centered design to
      establish the mathematical model of the selected responses in function of
      experimental factors. The chiral selector concentration, percentage of the
      capillary filled with the chiral selector, and drying gas nebulization pressure
      were three relevant factors taken into consideration. For each CD, the methadone
      enantiomeric resolution, apparent selectivity, and migration time of the second
      enantiomer were established as responses. The latter were systematically related
      to experimental parameters with the help of multiple linear regression. It is
      noteworthy that the behaviour was different in function of the chiral selector
      charge. Results revealed that the nebulization pressure involved in the
      electrospray process and the CD concentration had a significant effect on the
      enantiomeric resolution, while the effect of the separation zone length was less
      pronounced. Finally, response surfaces were drawn from the mathematical model and
      experimental conditions were selected to allow a robust determination of
      methadone enantiomers by CE-MS.

PMID- 11589297
TI  - Effect of organic solvent, electrolyte salt and a loading of cellulose tris (3,5
      dichlorophenyl-carbamate) on silica gel on enantioseparation characteristics in
      capillary electrochromatography.
AB  - The effect of the amount of the chiral selector, cellulose tris(3,5
      dichlorophenylcarbamate) (CDCPC) on the separation characteristics of enantiomers
      of some charged and neutral analytes was studied in capillary
      electrochromatography (CEC). For better understanding of the effect of the
      loading of the chiral selector on the particles and pore size of the packing
      material, laser-beam particle size analyzer and scanning electron microscopy
      (SEM) were used. As shown in this study, CDCPC can be used for CEC
      enantioseparations of a wide range of chiral charged and neutral analytes with
      high efficiency. The loading of the polysaccharide derivative on the surface of
      silica materials even in high amounts does not markedly affect the particle size
      and porous structure of the packing material. The separation characteristics are
      strongly affected by the loading of CDCPC onto silica gel in both CEC and
      capillary liquid chromatography (CLC).

PMID- 11589298
TI  - Continuous beds with vancomycin as chiral stationary phase for capillary
      electrochromatography.
AB  - Enantiomeric separations in capillary electrochromatography (CEC) carried out
      using a continuous-bed chiral stationary phase (CSP) based on the macrocyclic
      antibiotic, vancomycin, is presented. The continuous beds were prepared from
      methacryloxypropyl modified fused silica capillaries (100 microm ID) by in situ
      copolymerization of N-(hydroxymethyl)acrylamide and piperazine diacrylamide with
      vinyl sulfonic acid comonomer used to introduce ionic functionality and thus a
      strong electroosmotic flow (EOF). The CSP was subsequently prepared by
      immobilizing the vancomycin stationary phase by reductive amination. Preliminary
      results have indicated that an extremely strong EOF is obtained in both the
      nonaqueous polar organic (15.2 x 10(-5) cm2 V(-1) s(-1) and the aqueous reversed
      phase modes of operation (8.5 x 10(-5) cm2 V(-1) s(-1)). Enantioselectivity was
      obtained for four racemic compounds, the best of which was in the case of
      thalidomide which was separated in 10 minutes with high resolution (Rs = 2.5) and
      efficiency (120,000 plates meter(-1)) values.

PMID- 11589299
TI  - Chemically L-prolinamide-modified monolithic silica column for enantiomeric
      separation of dansyl amino acids and hydroxy acids by capillary
      electrochromatography and mu-high performance liquid chromatography.
AB  - A silica-based chiral monolithic column prepared by sol-gel process and chemical
      modification of chiral selector was used for enantioseparation of dansyl amino
      acids and hydroxy acids by capillary electrochromatography (CEC) and mu-high
      performance liquid chromatography (mu-HPLC). L-Prolinamide was modified as a
      chiral selector. The chiral stationary phase (CSP), the chiral complex of Cu(II)
      with L-prolinamide, provides an anodic electroosmotic flow (EOF) in CEC. The EOF
      was found to be dependent on applied electric field strength, the pH, and the
      composition of mobile phases. Scanning electron micrograph showed that monolithic
      columns have the morphology of continuous skeleton and large through-pore. D
      Enantiomers migrated before L-enantiomers except for dansyl-(Dns)-DL-Ser. The
      separation efficiencies of up to 17600 (D) and 13,200 plates m(-1) (L) were
      achieved for the separation of DL-indole-3-lactic acid.

PMID- 11589300
TI  - Isotachophoresis separations of enantiomers on a planar chip with coupled
      separation channels.
AB  - The use of a poly(methylmethacrylate) chip, provided with a pair of on-line
      coupled separation channels and on-column conductivity detectors, to
      isotachophoresis (ITP) separations of optical isomers was investigated. Single
      column ITP, ITP in the tandem-coupled columns, and concentration-cascade ITP in
      the tandem-coupled columns were employed in this investigation using tryptophan
      enantiomers as model analytes. Although providing a high production rate (about 2
      pmol of a pure tryptophan enantiomer separated per second), single-column ITP was
      found suitable only to the analysis of samples containing the enantiomers at
      close concentrations. A 94-mm separation path in ITP with the tandem-coupled
      separation channels made possible a complete resolution of a 1.5 nmol amount of
      the racemic mixture of the enantiomers. However, this led only to a moderate
      extension of the concentration range within which the enantiomers could be
      simultaneously quantified. The best results in this respect were achieved by
      using a concentration-cascade of the leading anions in the tandem-coupled
      separation channels. Here, a high production rate, favored in the first
      separation channel, was followed by the ITP migration of the enantiomers in the
      second channel under the electrolyte conditions enhancing their detectabilities.
      In dependence on the migration configuration of the enantiomers, this technique
      made possible their simultaneous determinations when their ratios in the loaded
      sample were 35:1 or less (D-tryptophan a major constituent) and 70:1 or less (L
      tryptophan a major constituent).

PMID- 11589301
TI  - Characterization and drug sensitivity of four newly established colon
      adenocarcinoma cell lines to antifolate inhibitors of thymidylate synthase.
AB  - Four new cell lines were established from the primary tumors of patients with
      untreated colorectal adenocarcinoma. Drug sensitivity and characterization of
      these cell lines was performed. Three of the four cell lines formed colonies in
      soft agar and all were tumorigenic in nude mice. The cell lines were
      morphologically similar but had differences in growth characteristics. Two of the
      cell lines, C18 (CCCL-4) and C29 (CCCL-6), had a longer doubling time compared
      with C85 (CCCL-1) and C86 (CCCL-2). The C18 and C29 cell lines had chromosome 17
      abnormalities and evidence by immunohistochemistry of a mutant p53 and had
      decreased levels of thymidylate synthase and dihydrofolate reductase proteins,
      associated with decreased thymidylate synthase catalytic activity in C18 and no
      detectable activity in C29. Raltitrexed and GW1843U89 showed potent cytotoxic
      activity and all four cell lines displayed similar cytotoxicity to these folate
      thymidylate synthase inhibitors. The C18 and C29 cell lines were in general
      resistant to the other agents tested (methotrexate, 5-fluorouracil, nolatrexed)
      when compared with the C85 and C86 cell lines. These new cell lines may be useful
      for the study of colorectal adenocarcinoma and for evaluating new drugs or
      treatment schedules.

PMID- 11589302
TI  - Selective susceptibility of transformed T lymphocytes to induction of apoptosis
      by PSC 833, an inhibitor of P-glycoprotein.
AB  - P-glycoprotein is a cellular efflux pump. The P-glycoprotein inhibitor PSC 833
      causes apoptosis of cancer cells and induces a rise in the intracellular levels
      of ceramide. Our aims were to determine whether a cause and effect relationship
      exists between these two actions of PSC 833, and to assess whether the PSC 833
      induced apoptosis is restricted to transformed cells. Apoptosis was determined by
      flow cytometry and radioactive quantitation of DNA fragmentation. PSC 833 induced
      apoptosis in the human T leukemia cell lines: Molt-4 and Jurkat. Analysis of the
      apoptosis in Molt-4 and Jurkat cells revealed that PSC 833 induced a rise in the
      cellular ceramide levels (as measured by the DG kinase assay). PSC 833-induced
      apoptosis was significantly reduced by specific inhibitors of ceramide de novo
      synthesis (i.e., fumonisin B1 and L-cycloserine). On the other hand, PSC 833 did
      not induce apoptosis in normal peripheral blood T cells regardless of whether
      these cells were quiescent, activated, or proliferating. Our results suggest that
      PSC 833 induces apoptotic death in human transformed T lymphocytes through an
      increase in ceramide de novo synthesis. In addition, normal lymphocytes are not
      susceptible to induction of apoptosis by PSC 833. This difference between normal
      lymphocytes and leukemia cells presents a potential target for chemotherapy.

PMID- 11589303
TI  - 4-[3-(2-Nitro-1-imidazolyl)propylamino]-7-chloroquinoline hydrochloride (NLCQ-1),
      a novel bioreductive agent as radiosensitizer in vitro and in vivo: comparison
      with tirapazamine.
AB  - The novel hypoxia-selective cytotoxin NLCQ-1, which is a weak DNA intercalator,
      was studied in conjunction with radiation against V79 cultured cells and EMT6 or
      SCCVII tumors in their syngeneic mice and compared with tirapazamine (TPZ). NLCQ
      1 was a very potent and efficient radiosensitizer of hypoxic V79 cells, providing
      SER values of 2.27-2.56 at 20-80 microM concentration (measured at 10% survival
      level). Its C1.6 (concentration for an SER of 1.6 to be obtained) was 7.2+/-0.2
      microM. Its in vitro therapeutic index (ThI, defined as CT50(Air),/C1.6) varied
      by the exposure time from 57 (1-h exposure) to 145 (4.5-h exposure). The
      corresponding C1.6 value for TPZ was 16.9 microM whereas its in vitro therapeutic
      index was 49 (3-h exposure). A schedule-dependent synergistic interaction was
      observed between NLCQ-1 or TPZ and 20 Gy of radiation in both tumor models
      examined, by using the in vivo-in vitro assay as endpoint. Optimal synergism (> 1
      log) was observed in EMT6 tumors when each bioreductive drug was given between 45
      and 60 min before irradiation. NLCQ-1 alone had no significant antitumor activity
      at 10 mg/kg (28% of its single LD50), whereas a 0.4 surviving fraction was
      obtained by TPZ at 30 mg/kg (38% of its single LD50). SER values of 1.52 and 1.25
      were obtained with 10 mg/kg NLCQ-1 and 30 mg/kg TPZ, respectively, in EMT6
      tumors. An SER value of 1.58 was obtained for both hypoxia-selective cytotoxins,
      at equitoxic doses, in SCCVII tumors, by using a fractionated regimen. These
      results suggest a possible use of NLCQ-1 or TPZ as adjuvants to radiotherapy.

PMID- 11589305
TI  - ATF3 gene regulates cell form and migration potential of HT29 colon cancer cells.
AB  - We formally reported that ATF3 gene regulated HT29 colon cancer cell metastasis
      through cell adhesion and invasion. We report here our findings that, on wound
      filling assay, the ATF3 antisense oligonucleotide changed cell form to a rounder
      shape and suppressed the cell migration ability of HT29, although FACScan
      analysis showed that it had no effect on the cell cycle. The growing area of HT29
      cells treated with the antisense oligonucleotide decreased, compared with that
      treated with the sense oligonucleotide. These factors were thought to relate to
      adhesion and invasion of HT29 cells, hence they influenced metastatic potential.

PMID- 11589304
TI  - Demethylation by 5-aza-2'-deoxycytidine (5-azadC) of p16INK4A gene results in
      downregulation of vascular endothelial growth factor expression in human lung
      cancer cell lines.
AB  - Vascular endothelial growth factor (VEGF) plays a pivotal role in tumor
      progression via angiogenesis. Recently, gene transduction of wild-type p16INK4A,
      tumor suppressor gene, has been shown to result in downregulation of VEGF
      expression in p16INK4A-deleted glioma cells. Because expression of p16INK4A is
      regulated by methylation of the p16INK4A gene, we examined whether demethylation
      of the p16INK4A gene by 5-aza-2'-deoxycytidine (5-azadC) could cause the protein
      expression of VEGF as well as of p16INK4A in human lung cancer cells. For this,
      five different lung cancer cell lines with or without loss of p16 activity were
      used. H841 and Ma-10 cells had the methylated p16INK4A gene without expression of
      p16INK4A protein, whereas Ma-1 and H209 cells had the unmethylated p16INK4A gene
      with constitutive expression of p16INK4A protein. Neither the p16INK4A gene nor
      p16INK4A protein was detected in A549 cells. Treatment with 5-azadC caused
      demethylation of the p16INK4A gene with reexpression of p16INK4A protein in H841
      and Ma-10 (methylated p16INK4A gene dominant) cell, but not in other cell lines
      such as Ma-1, H209 (unmethylated p16INK4A gene dominant), or A549 (p16INK4A gene
      deleted). In a parallel experiment, 5-azadC inhibited production of VEGF protein
      by H841 and Ma-10 cells, especially in the later hypermethylated cells, but not
      Ma-1, H209, or A549 cells. RT-PCR analysis showed that Ma-10 cells expressed VEGF
      isoforms 121, 165, and 189, all of which were inhibited by 5-azadC. These
      findings indicate that the methylation status of the p16INK4A gene plays an
      important role in the regulation of angiogenesis associated with progression of
      lung cancer, through regulation of VEGF expression.

PMID- 11589307
TI  - Downregulated expression of Ly-6-ThB on developing T cells marks CD4+CD8+ subset
      undergoing selection in the thymus.
AB  - Interaction of TCRs on CD4+CD8+ immature T cell with MHC-peptide complexes on
      stromal cells is required for positive and negative selection in the thymus.
      Identification and characterization of a subpopulation of CD4+CD8+ thymocytes
      undergoing selection in the thymus will aid in understanding the mechanisms
      underlying lineage commitment and thymic selection. Herein, we describe the
      expression of Ly-6 ThB on developing thymocytes. The majority of CD4+CD8+
      thymocytes express Ly-6 ThB at high levels. Its expression is downregulated in a
      subset of CD4+CD8+ thymocytes as well as in mature CD4+CD8- and CD4-CD8+ T cells.
      More importantly, interaction of TCR/coreceptor with the self-MHC-peptide
      contributes to the downregulation of ThB expression on developing thymocytes.
      These findings indicate that downregulation of ThB on CD4+CD8+ thymocytes
      identifies a unique subset (CD4+CD8+ThBneg-low) of thymocytes that has received
      the initial signals for thymic selection but have not yet downregulated the CD4
      and CD8 cell surface expression. In addition, these results also indicate that a
      high frequency (approximately 20-40%) of CD4+CD8+ immature thymocytes receive
      these initial signals during thymic selection.

PMID- 11589306
TI  - Human papilloma virus 16 E7 oncogene does not cooperate with RET/PTC 3 oncogene
      in the neoplastic transformation of thyroid cells in transgenic mice.
AB  - We have previously reported that the thyroid-targeted expression of the RET/PTC3
      oncogene (Tg-RET/PTC3) in transgenic mice induces follicular hyperplasia with
      papillary architecture, resulting in a modest increase of the thyroid gland
      volume, followed by the appearance of papillary carcinomas in approximately 1
      year-old animals. In order to analyze the genetic alterations that may cooperate
      with RET/PTC3 in the development or progression of thyroid tumors, we interbred
      Tg-RET/PTC3 mice with Tg-E7 transgenic mice, which express the E7 oncogene of the
      human papilloma virus 16 in thyroid cells. Tg-E7 mice develop large colloid
      goiters with small papillae and well-differentiated thyroid carcinomas in older
      animals. Here we show that thyroid lesions in Tg-RET/PTC3-Tg-E7 double
      transgenics were morphologically different from those occurring in Tg-RET/PTC3
      mice, while they were virtually indistinguishable from those occurring in Tg-E7
      mice. In addition, the coexpression of RET/PTC3 and E7 oncogenes neither enhanced
      the malignant phenotype nor reduced the latency period of thyroid lesions with
      respect to parental transgenic lines. We conclude that the coexpression of
      RET/PTC3 and E7 lacks any cooperative effect in the neoplastic transformation of
      thyroid cells and that the E7-induced thyroid phenotype is dominant with respect
      to the RET/PTC3 one.

PMID- 11589308
TI  - The effect of antigen stimulation on the migration of mature T cells from the
      peripheral lymphoid tissues to the thymus.
AB  - Although the maturation and export of T cells from the thymus has been
      extensively studied, the movement of cells in the opposite direction has been
      less well documented. In particular, the question of whether T cells which have
      been activated by antigen in the periphery are more likely to return to the
      thymus had been raised but not clearly answered. We examined this issue by
      activating T cells present in the periphery with their cognate antigen, and
      assessing migration to the thymus. TCR-transgenic cells from OT-I mice (Thy1.2+),
      which recognise the ovalbumin peptide OVA257-264 in the context of H-2Kb, were
      transferred into otherwise unmanipulated Thy1.1+ C57BL/6 mice. Recipient mice
      were injected i.v. with 5 microg peptide (SIINFEKL) approximately 24 hours later.
      The numbers of donor-derived (Thy1.2+) cells in the thymus and peripheral
      lymphoid tissue were determined. The results clearly show increased numbers of
      transgenic cells in the thymus 3 days after antigenic stimulation. However, since
      numbers of transgenic cells increased in the spleen and LN in about the same
      proportion, the data do not support the notion that there is highly increased
      selective migration of activated T cells to the thymus. Rather, they suggest that
      a sample of peripheral cells enters the thymus each day, and that the mature
      immigrants detected in the thymus merely reflect the contents of the peripheral T
      cell pool.

PMID- 11589309
TI  - Development of dendritic cells from GM-CSF-/- mice in vitro : GM-CSF enhances
      production and survival of cells.
AB  - The production of dendritic cells (DC) from haemopoietic progenitors maintained
      in long term stroma-dependent cultures (LTC) of spleen or bone marrow (BM) occurs
      independently of added granulocyte/macrophage colony stimulating factor (GM-CSF).
      The possibility that cultures depend on endogenous GM-CSF produced in low levels
      was tested by attempting to generate LTC from spleen and BM of GM-CSF-/- mice.
      Multiple cultures from GM-CSF-/- and wild type mice were established and compared
      for cell production. GM-CSF-/- LTC developed more slowly, but by 16 weeks
      produced cells resembling DC in numbers comparable to wild type cultures. LTC
      maintained distinct populations of small and large cells, the latter resembling
      DC. Cells collected from GM-CSF-/- LTC were capable antigen presenting cells
      (APC) for T cell stimulation and morphologically resembled DC. Large cells
      expressed the CD11b, CD11c, CD86, 33D1 and Dec-205 markers of DC. Addition of GM
      CSF to GM-CSF-/- LTC increased the proportion of large, mature DC present in
      culture. Stromal cells from GM-CSF-/- LTC could support the differentiation of DC
      from early progenitors maintained in LTC without addition of GM-CSF. However, GM
      CSF is not a critical factor in the in vitro generation of DC from progenitors.
      It can, however, substitute for stromal cells in increasing the survival of
      mature DC.

PMID- 11589310
TI  - Development of intraepithelial cells in the porcine small intestine.
AB  - The number, phenotype, localisation and development of intraepithelial
      lymphocytes (IEL) from duodenum (Du) and ileum (Il) were studied by
      immunohistochemistry (IHC) and light and electron microscopy in unweaned (0-7
      weeks old) and six months-old pigs. Developmental changes at birth showed that
      38% of the total lymphocytes in the villi were IEL, mainly of the CD2+CD4-CD8-
      double negative (DN) phenotype. That proportion rose to over 50% at week 5 after
      birth, resembling adult proportion, although still with fewer cells than in adult
      pigs. CD4+ cells appeared relatively early in life although they were confined to
      the lamina propria (LP) and CD8+ cells were found only in low numbers. In the
      villi of adult animals, almost half of the total number of lymphocytes were IEL
      (49% Du, 52% Il). Over half of these IEL (52% Du, 53% Il) showed the CD2+CD4-CD8+
      phenotype and were localized at the epithelium's basement membrane. Numerous (43%
      Du, 42% Il) DN IEL were found grouped at the enterocyte nucleus level and
      relatively few (5% in Du and Il) granular IEL were found apically in the
      epithelium. These proportions were homogeneously maintained along the villi's
      tip, middle and bottom, suggesting that the IEL may have their origin in the LP.
      Therefore, the IEL compartment in the porcine intestine develops slowly with age
      and is actually composed by a heterogeneous population of cells (null, DN and
      CD8+). These results may explain the increased susceptibility of young animals to
      disease during the lactation period and should be taken into account when
      functional studies are carried out with IEL. The quantitative results of this
      paper established a model for studies on the effect of age, diet, normal flora,
      infection and oral immunization on the IEL of the gut.

PMID- 11589311
TI  - Peyer's patches are precocious to the appendix in human development.
AB  - PP are first visible at approximately 15.5 wk gestation after which there is a
      rapid spurt in the development and maturation of lymphoid follicles so that at
      any given point of time new foci of PP development are continuously formed at a
      rapid rate. Addition of rows of follicles results in the formation of a PP.
      Immature PP of younger fetuses have a spongy structure in contrast with the
      compact lymphoid follicles of mature PP of older fetuses. Immunocytochemical
      studies reveal that there is a subtle gradation in the expression of lymphocyte
      surface markers with increasing fetal age. Expression of antigenic markers occurs
      in an ordered sequence viz. HLA - DR, CD19 (B cell population), CD9 (pre-B
      cells), CD3 T lymphocytes, CD4 helper / inducer lymphocytes, the CD8 suppressor /
      cytotoxic cells and lastly, the CD57 Natural Killer cells. The antigens are
      expressed first on lymphocytes of PP and thereafter in those of the appendix. Our
      findings clearly demonstrate that the approximately 5 wk fetal period from 17.5
      wk to 22 wk represents a major growth phase in the development of surface markers
      of lymphocytes in the mucosal immune system of the gut.

PMID- 11589312
TI  - Antibodies to human thymic epithelium form part of the murine autoreactive
      repertoire.
AB  - Monoclonal antibody (mAb) MR6 recognises a 200 kDa glycoprotein, gp200-MR6, which
      is expressed at high levels on the surface of human thymic cortical epithelium.
      In order to produce further mAbs against the gp200-MR6 molecule, mice were
      immunised with purified human gp200-MR6, hybridomas produced and supernatants
      screened for MR6-like reactivity on human thymic sections. Surprisingly this
      conventional hybridoma technique failed to produce stable hybridoma cells
      producing MR6-like antibodies. However, antibodies with specificities other than
      MR6-like were obtained. Three such antibodies (1B2, 3A3 and 4B3) were analysed
      further. Expression of 1B2-antigen, 3A3-antigen and 4B3-antigen was analysed on
      skin, tonsil and thymic sections, on cultured thymic epithelial cells (TEC),
      thymocytes and peripheral blood mononuclear cells (PBMC), and found to be
      expressed by both lymphocytes and epithelial cell populations. Furthermore, the
      antigens were also expressed on mouse thymic epithelial cells. The regulation of
      expression of these antigens was analysed following mitogen or cytokine
      stimulation of PBMC and cultured TEC, respectively. Expression on T cells was
      clearly affected by mitogens that mimic activation through the T cell receptor
      and expression on cultured TEC was affected by T cell-derived cytokines. Thus,
      the shared epithelial-lymphocyte molecules identified in this study may play a
      role in the cross-talk between the developing thymocytes and their epithelial
      microenvironment. The production of mAbs with specificities other than that of
      purified gp200-MR6 indicates that a wide range of B cells with specificity for
      components of the human thymic microenvironment exist in the normal mouse. These
      may detect epitopes that are shared with common pathogens to which the animals
      are exposed. Alternatively, they may be autoreactive B cells that are normally
      silent in the absence of T cell help. This help may be provided by T cells
      specific for human gp200-MR6, or nonspecifically by polyclonal activation induced
      by the adjuvant.

PMID- 11589313
TI  - Gender-related differences in the rates of age associated thymic atrophy.
AB  - Age associated thymic atrophy has been shown to be linked to problems with
      rearrangement of the beta chain of the T cell receptor (TCR) in male mice during
      the early phases of the intrathymic T cell developmental pathway. In this study,
      thymic atrophy in female mice was found to occur at a different rate than in male
      mice. At 9 months of age there was a significantly greater number of cells in the
      thymus of female mice compared with male mice, with the major difference found in
      the CD4+CD8+ populations. The thymii of female mice at 9 months of age contained
      double the number of these cells compared with male mice. Analysis of the
      CD4+CD8+ cells at 9 months of age demonstrated increased numbers of cells
      expressing higher levels of CD3 in females compared with males indicating that in
      females more of these cells were producing successful alphabetaTCR pairings. In
      F5 transgenic mice comparison of the CD4+CD8+ population revealed no significant
      difference in their absolute numbers at 9 months of age. These results indicate
      that the gender differences at this time point were due to fewer permitted
      divisions prior to the expression of a selectable TCR alpha chain within the
      CD4+CD8+ populations in male compared with female mice. This gender difference
      was not due to the action of testosterone and unlikely to be due to differences
      in the level of oestrogen. The potential mechanisms of this difference may be
      related to a regulatory feedback of peripheral T cells on the developing
      thymocyte populations. Such age related changes in the numbers of cells within
      distinct thymic subpopulations leads to the possibility that the potential
      repertoire in females is greater than in males later in life.

PMID- 11589314
TI  - A new classification of malformations of the nervous system: an integration of
      morphological and molecular genetic criteria as patterns of genetic expression.

PMID- 11589315
TI  - Canavan disease: a review of recent developments.
AB  - The clinical features, causes and potential treatment of Canavan disease are
      reviewed. The course of the illness can show considerable variation, and can
      sometimes be protracted. It has an autosomal recessive mode of inheritance, and
      is caused by mutations in the gene for aspartoacetylase, localized to the short
      arm of chromosome 17. The changes in the central nervous system are related to
      the deficiency of aspartoacyclase which leads to an excess of N-acetylaspartate.
      Prenatal diagnosis of Canavan disease is possible by the measurement of N
      acetylaspartate in the amniotic fluid, but the method of choice is by DNA
      analysis. If an infant is suspected of having the disease, due to megalencephaly
      and clinical deterioration, the diagnosis can be confirmed by elevated N
      acetylaspartate levels in the urine, blood, and spinal fluid--and in the brain
      using proton magnetic resonance spectroscopy. Neuroradiological investigations
      confirm the white matter degeneration. Reports of children with megalencephaly,
      and similar clinical findings, but with normal metabolic tests, are also
      considered. Until recently treatment was symptomatic, such as the control of
      seizures, but now there is a possibility though not yet proven, of using gene
      therapy with modification of the phenotype of brain cells while bypassing the
      blood-brain barrier and the ependyma. This seems to be well tolerated, and was
      associated with biochemical, radiological, and clinical changes. The development
      of knockout mice for Canavan disease should help in the development of gene
      transfer vectors to treat Canavan disease and for understanding the
      pathophysiology.

PMID- 11589316
TI  - Arithmetic skills in kindergarten children with developmental language disorders.
AB  - Although arithmetic is not a language-based skill, a specific learning disability
      in arithmetic--dyscalculia--is commonly seen in children with developmental
      language disorders (DLD). The object of this study was to assess whether
      kindergarten children with DLD have impaired arithmetic skills and, if so, to
      correlate the pattern of dysfunction with language syndromes. Forty-two children
      with DLD attending mainstream kindergartens, and their matched controls,
      underwent an arithmetic battery, neurological examination, intelligence quotient
      (IQ) test (WPPSI/WISC-R) and language assessment (CELF-R).* Attention deficit
      hyperactivity disorder (ADHD) was diagnosed by psychological assessment and
      behaviour questionnaires. Results showed that children with DLD were similar to
      controls on performance IQ (104.2+/-12.1 and 109.4+/-12.7 respectively, p = NS),
      but inferior on both the CELF-R expressive (74.8+/-9.3 vs 95.2+/-15.1, p < 0.01)
      and receptive (77.5+/-10.0 vs 87.8+/-12.3, p < 0.01) language scores. Their
      performance on the arithmetic battery was also significantly poorer: 61.2+/-17.7
      vs 77.4+/-13.7, p < 0.01. Low scores in reasoning principles and arithmetic
      operations were associated with both receptive and expressive language
      impairment, while poor performance on counting principles was primarily
      associated with expressive deficits. Mild motor signs and ADHD were more frequent
      in children with DLD (p < 0.01 and < 0.05, respectively). We concluded that the
      arithmetic impairment in children with DLD is pervasive, affecting a broad
      spectrum of skills. Whereas impairment of most arithmetic skills is associated
      with global language disturbances, counting correlates primarily with expressive
      language deficits. Anticipatory guidance by physicians will better prepare
      parents and educators for the multiple challenges facing children with DLD.

PMID- 11589317
TI  - Bilateral subdural collections--an unusual feature of possible Kawasaki disease.
AB  - A case of possible Kawasaki disease presenting with bilateral subdural
      collections is reported. A 6-month-old boy was admitted to hospital following a
      prolonged partial seizure. He showed signs of worsening encephalopathy and was
      treated for presumed infective meningoencephalitis. Imaging revealed bilateral
      subdural collections. Pyrexia and irritability continued despite appropriate
      antibiotic and antiviral therapy suggesting a vasculitic process. The
      mucocutaneous signs normally associated with Kawasaki disease were subtle and
      fleeting in this infant. There was a dramatic clinical response to intravenous
      immunoglobulin and high dose aspirin. At 2-year follow-up the boy has made a
      complete recovery with no echocardiographic evidence of coronary artery aneurysm
      and resolution of subdural collections. Kawasaki disease or other vasculitides
      should be considered in the differential diagnosis of acute subdural collections
      in infancy.

PMID- 11589318
TI  - Two cases of influenza with impaired ocular movement.
AB  - Complications of influenza include respiratory disorders (pneumonia, bronchitis
      and croup) and occasionally myocarditis, myositis, encephalitis, encephalopathy
      and Reye's syndrome, which may be life-threatening and cause various sequelae. We
      report two patients who developed unusual complications of influenza infection:
      one had ptosis and impaired ocular movement, and the other suffered from Guillain
      Barre syndrome with paralysis of the extraocular muscles.

PMID- 11589319
TI  - Congenital myopathies.

PMID- 11589320
TI  - Mesenteric angina complicating a mesodermal anomaly. R Howells et al. Eur J
      Paediatr Neurol 2000 4(4): 181-184.

PMID- 11589321
TI  - Paediatric neurology in Israel?

PMID- 11589322
TI  - Differential psychotic symptomatology in polyglot patients: case reports and
      their implications.
AB  - Polyglot psychotic patients can present with either different or less psychotic
      symptoms depending on the language they use. No known study has used a structured
      interview to assess such differences. A language history was taken on three
      patients who were then assessed using the Positive and Negative Syndrome Scale
      structured interview (SCI-PANSS) for schizophrenia in their two languages. All
      three patients were found to have different positive symptoms depending on the
      language used in the interview procedure by the same bilingual researcher. These
      findings could have important implications in terms of our assessment and
      treatment of psychotic patients in the NHS. They demonstrate the need to carry
      out a large study in order to determine how common these findings are in
      multilingual patients.

PMID- 11589323
TI  - Faith conquers all? Beliefs about the role of religious factors in coping with
      depression among different cultural-religious groups in the UK.
AB  - How effective is religious activity believed to be in coping with depression?
      This study assessed the perceived effectiveness of different religious activities
      -previously identified as important in coping--among 282 people in the UK. The
      mean age was 25 years, and participants were either Christian, Hindu,Jewish,
      Muslim, other religion, or no religion. Relative to other kinds of help for
      depression, religious activity was not seen as particularly helpful for
      depression. Religious activity was seen as less helpful by the ever-depressed
      than by the never-depressed and as less helpful by women than by men. Among
      religious activities, faith and prayer were seen as the most helpful. Muslims
      believed more strongly than other groups in the efficacy of religious coping
      methods for depression, were most likely to say they would use religious coping
      behaviour, and were least likely to say they would seek social support or
      professional help for depression. Other differences between groups were also
      observed, and comparisons with qualitative material obtained in an earlier study
      were made. The implications of these findings for help-seeking are considered.

PMID- 11589324
TI  - Contingent reinforcement or defending the self? A review of evolving models of
      aggression in people with mild learning disabilities.
AB  - This paper examines the changing approaches to working with people with a
      moderate to mild learning disability, who are frequently aggressive. Long-held
      assumptions about the lack of inter-personal understanding and impulsiveness
      continue to play a central role in clinical assessment and intervention for this
      group. Yet, there is a lack of controlled studies indicating the influence of
      such factors in frequent aggression. The dominant behavioural tradition has long
      encouraged such assumptions, but has focused on people with more severe
      disabilities where such assumptions are arguably more appropriate. The current
      review of the literature shows a clear evolution away from a strict behavioural
      approach towards cognitive-behavioural therapy (CBT) approaches that take account
      of the heterogeneous psychosocial causes of aggression. We find support for CBT
      in the child-development literature, which examines inter-personal difficulties
      from an information-processing perspective. Finally, we argue that much of the
      literature implicitly utilizes the concept of self, and we suggest that this
      should be made explicit in a reformulated theory of the 'person', incorporating
      the self concept and embedding individual cognitive processes and behaviour in a
      social context.

PMID- 11589325
TI  - The Bene-Anthony Family Relations Test revisited: directions in the assessment of
      children's perceptions of family relations.
AB  - The Bene-Anthony Family Relations Test is designed to assess the child's
      perception of family relations using projective techniques. This article
      describes the test and background to its development. The validity of the test is
      limited by the content of some items and their categorization, though there is
      evidence that the test can distinguish between populations that differ on other
      related variables. A survey of professionals who use the test is described.
      Despite their enthusiasm for it, the majority of respondents had modified the
      test in some way, and 86% regularly rephrased at least one item from the test.
      There were several criticisms of the test, including the positive scoring of
      'sexualized items'. The respondents were also inconsistent in their
      administration and scoring of the test. This test is used less frequently in
      research, possibly because it is not perceived as a sufficiently robust
      psychometric instrument. However, there is a danger of 'throwing away the baby
      with the bath water'. Recommendations are made for the development of a test that
      reliably assesses the child's perception of the emotional content of relations.

PMID- 11589326
TI  - Psychoeducation in the prevention of eating disorders: an experimental approach
      in adolescent schoolgirls.
AB  - The aim of this report is to analyse the impact of a psychoeducational preventive
      programme on the eating habits of a sample of adolescent schoolgirls. Of the 112
      schoolgirls attending five classes, about 86% agreed to participate in the
      program. Of these, 63 participants belonged to the experimental group and 33
      agreed to the control group. The psychoeducational sessions were performed once a
      month for each of three experimental classes. The programme involved discussions
      on the nature of eating disorders, on epidemiological aspects and on the
      importance of early detection of risk factors. The tests used to evaluate the
      sample were the EDI-2 and the PF-16. The results showed a significant improvement
      in bulimic attitudes, asceticism, feelings of ineffectiveness, and maturity
      fears. Anxiety traits were also better managed in the experimental group. Our
      conclusions suggest that correct information about eating disorders can
      ameliorate unhealthy attitudes towards eating behaviour.

PMID- 11589327
TI  - Cultural stereotype of the effects of religion on mental health.
AB  - To examine if the religious are more likely to be rated as having a poorer mental
      health than the non-religious, 48 Northern Irish undergraduate students completed
      self-report measures of religious attitude and mental health under four counter
      balanced conditions: 'control' (present yourself 'as you really are') and as how
      'religious', 'nonreligious', and 'mentally ill' respondents might be thought to
      answer. The 'religious' condition provided significantly higher scores for both
      the Obsessional Symptom Scale and the Obsessional Personality Trait Scale and
      significantly lower Psychoticism Scale scores than the 'non-religious' condition.
      Moreover, significant associations were found between higher scores on the
      religiosity scale and higher scores on the Obsessional Personality Trait Scale in
      two of the four conditions ('religious' and 'mentally ill') and lower scores on
      the Psychoticism Scale in three of the four conditions ('control', 'religious',
      and 'mentally ill'). These results suggest that the religious are viewed
      paradoxically as having both aspects of better (i.e. lower psychoticism scores)
      and poorer mental health (i.e. higher obsessional scores) than the non-religious.
      As such, the present findings provide some support for the existence of a
      powerful cultural stereotype of the religious.

PMID- 11589328
TI  - Intensive care unit syndrome: a consideration of psychological interventions.
AB  - There is little in the psychological literature to guide clinicians treating ICU
      patients presenting with the ICU syndrome. Existing psychological models need to
      be developed and adapted in the management of these cases. This paper describes
      two clinical cases and offers psychological formulations and descriptions of
      treatment.

PMID- 11589329
TI  - Personal constructs, childhood sexual abuse and revictimization.
AB  - Within the theoretical framework of Ryle's Procedural Sequence Object Relations
      Model and Kelly's Personal Construct Theory, this study investigates sex-role
      polarization of incest survivors and the centrality of abuse within survivors'
      constructs of men that may contribute to revictimization. Repertory grid
      methodology was used with 40 female survivors of childhood sexual abuse and 28
      non-abused women. Grid measures and psychometric measures were compared between
      groups of women who had and had not experienced childhood sexual abuse,
      revictimized and non-revictimized survivors, and survivors who had and had not
      experienced incestuous abuse. Results showed significant differences between
      survivors and non-abused women, with survivors having higher levels of depression
      and perceived distress, lower self-esteem and higher self/ ideal self
      discrepancy. Hypothesized differences in sex-role polarization were not found.
      There were few differences between revictimized and non-revictimized survivors,
      although revictimized survivors rated 'self now' as more powerful than non
      revictimized survivors. No differences were found between survivors who had and
      had not experienced incestuous abuse. In addition to the value of exploring
      personal constructs, a range of models need to be considered in understanding
      revictimization and women's construal of men. The implications of using repertory
      grid methodology for research and clinical work are discussed.

PMID- 11589330
TI  - Personal appraisal of the experience of a depressive disorder.
AB  - In a prospective study, 61 patients receiving ongoing treatment for Major
      Depression rated the personal significance of the disorder by using the Personal
      Appraisal Inventory (PAI) (Bookless, Clayer & McFarlane, 2000) twice over a
      period of 7 months. The initial (Time 1) association between the individual items
      of the PAI and self-reported levels of depression, anxiety, disability, self
      esteem and psychological distress was examined. It was found that these variables
      related to some items pertaining to appraisal of the harm and threat engendered
      by the disorder, but did not relate to appraisal of the positive and negative
      options for managing the disorder. Seven months later (Time 2) few significant
      changes were found in the way people appraised the impact of the disorder
      however, levels of depression, anxiety, disability and distress at Time 2 were
      predicted by several appraisal items. The clinical implications of these findings
      are discussed.

PMID- 11589331
TI  - Transcultural psychiatry: some social and epidemiological research issues.
AB  - BACKGROUND: Mental Health Research across cultural groups is often criticised for
      using imprecise measures of cultural group and for using outcome measures as if
      they have universal validity. AIMS: 1. To Investigate the effect of using
      different cultural group variables on the findings of a survey of prevalence of
      Common Mental Disorders. 2. To demonstrate that assumptions of validity for
      outcomes measures can affect the interpretation of data from prevalence surveys.
      METHODS: We recruited Punjabi and English subjects to a phase prevalence survey
      that included the Amritsar Depression Inventory and the General Health
      Questionnaire as screening instruments. The Clinical Interview Schedule was the
      outcome measure. This paper reports on a secondary analysis of the data. We used
      ethnic group, place of birth, religion, first language and language spoken at
      interview as possible cultural group variables and compared the prevalence
      estimates. We then considered the limitations of conventional methods to assess
      prevalence, by looking at mean scores on each of the three instruments in both
      cultural groups. RESULTS: Cultural group variables did not influence the
      prevalence estimates for Common Mental Disorder. Although conventional scoring
      methods showed no difference in prevalence across cultures, the mean scores on
      each instrument, when compared across cultural groups, differed for the Amritsar
      Depression Inventory. This instrument showed a higher mean score for the Punjabis
      suggesting a higher prevalence. The findings are discussed in the context of
      value laden 'assumptions' about validity. CONCLUSIONS: The findings of prevalence
      surveys depend on assumptions of validity. The 'culture' of psychiatry is a
      closed system in which validation studies support its basic assumptions.

PMID- 11589332
TI  - The linkages between gender and victimhood.
AB  - Victimhood, it is argued, is a term that is preferentially applied to and adopted
      by women. Victimhood is not a psychiatric diagnosis although psychological
      factors, such as gender development and sociological factors influence the
      acquisition of the victim role. This article reviews the sociological and
      psychological contributions to the labeling of a person as "victim." Victimhood
      is relevant to psychiatry because psychiatric patients often describe themselves,
      or are described as victims. Victimhood is generally seen as a negative
      identification, but this article will argue that identification as a victim is
      the first step in identifying the need for services.

PMID- 11589333
TI  - Case management: an update.
AB  - BACKGROUND: Case management in its various forms represents a major innovation in
      mental health care. Its efficacy remains controversial. AIMS: To update after a
      decade a previous review article (Holloway, 1991). METHODS: Descriptive
      literature and controlled trials of case management and its derivative Assertive
      Community Treatment (ACT) was accessed through four comprehensive and systematic
      reviews of the literature, repeated Medline and Embase searches and personal
      contacts. RESULTS AND CONCLUSIONS: The concept of case management has continued
      to evolve over the past decade. No controlled trial has been published exploring
      the model of the case manager as a service broker without responsibility for the
      provision of care. Basic case management principles have frequently been
      incorporated within routine clinical practice. Published controlled trials of
      ACT, which were almost exclusively carried out in North America, have shown
      markedly positive results. However caution is required in extrapolating these
      findings to routine clinical practice within different systems of health and
      social care. Case management is not in itself an effective treatment for severe
      mental illness.

PMID- 11589334
TI  - Social problems in Pakistani psychiatric patients.
AB  - The paper presents a case register-based descriptive survey of social problems of
      general hospital psychiatric patients in Pakistan. 47.2% of psychiatric patients
      had a social problem. Problems with primary support group occurred in 33.4%,
      14.2% had relational problems and 7.8% had problems relating to bereavement or
      death. Social problems were more common in females and patients who had
      adjustment disorder or depression. Psychiatric patients had more social problems
      than those who were diagnosed as having a physical problem only. Female depressed
      patients experienced problems with their in-laws more frequently than other types
      of social problem. The implications are that: i) some DSMIV categories require
      changing to make them more internationally applicable; ii) specific psycho-social
      inquiry during psychiatric diagnostic interviews is essential; iii) grief
      counselling and family therapy are important psychotherapeutic needs of Pakistani
      psychiatric patients; iv) these, in turn, indicate priorities in mental health
      professional training curricula.

PMID- 11589335
TI  - Ethnic and gender differences in mental health utilization: the case of Muslim
      Jordanian and Moroccan Jewish Israeli out-patient psychiatric patients.
AB  - A sample of 148 (87 Jordanian [61 male, 26 female] and 61 Israeli [26 male, 35
      female]) was selected from a psychiatric clinic in Ashdod Israel and Zarka
      Jordan, using convenience sampling methodology over a 12 month period in late
      1997 and early 1998. A revised Hopkins Symptom Checklist: A Self-Report Symptom
      Inventory (HSCL) was translated into Arabic and Hebrew and distributed to
      subjects; additional questions explored demographic characteristics, forms of
      received treatment, patient perceptions of treatment efficacy, patient use of
      traditional healers, and patient explanation of etiology. Data revealed that
      there were differences in dimensions between the 2 groups based on nationality
      and gender. More Jordanians than Israelis expected medications as the main
      treatment, and unlike Israelis, no Jordanian patients received individual
      psychotherapy. Israelis expected medications, advice, directions, and
      instructions from psychiatrists. Both ethnic groups consulted a wide array of
      traditional healers, although precise types of healers varied according to gender
      and ethnicity. Israeli subjects gave more diverse explanations of mental health
      etiologies: physical, family, divorce, economic, unemployment; whereas Jordanians
      tended to emphasize divine and spiritual sources. Implications for psychiatric
      practice are discussed.

PMID- 11589336
TI  - Home treatment.
AB  - BACKGROUND: Deinstitutionalisation has stressed where care is no longer taking
      place. Home treatment in rehabilitation reflects the steady increase in emphasis
      on support and treatment for individuals with long-term disorders where it
      matters for them--in their own homes. MATERIALS AND DISCUSSION: Whether dealing
      with individuals discharged after long periods in hospital or with the increasing
      number who have experienced repeated short-term admissions, most modern day
      rehabilitation takes place in the patients' homes and neighbourhoods. We are
      increasingly convinced that this decentralisation is a positive strength, not a
      problem. Its advantages include improving social inclusion and the ability to
      conduct more accurate, personalised assessments of disabilities and strengths.
      Skills training is more focused and we discuss the components of home treatment
      and assertive community treatment as they are relevant to rehabilitation. This
      involves both medication and practical help, brokerage and involvement with the
      voluntary sector. CONCLUSIONS: Rehabilitation remains, at its core, a set of
      relationships between whole individuals (not just skills and needs). A home-based
      approach is proposed as the norm, not the exception. It is based on a rounded
      understanding of the patient as a unique person and emphasises the importance of
      a strong working alliance.

PMID- 11589337
TI  - Quantitative and qualitative aspects of the social network in schizophrenic
      patients living in the community. Relationship to sociodemographic
      characteristics and clinical factors and subjective quality of life.
AB  - Quantitative and qualitative aspects of the social network were investigated in a
      sample of 120 schizophrenic out-patients. Sociodemographic and clinical factors
      as well as subjective quality of life were investigated as to their relationship
      to the social network. The Interview Schedule for Social Integration (ISSI) was
      used to assess social network and Lancashire Quality of Life Profile was used to
      assess subjective quality of life. Psychopathology was measured by BPRS and
      psychosocial functioning by GAF. The patients reported a significantly worse
      social network compared to a normal sample both regarding quantitative and
      qualitative aspects of the network. Almost half of the patients wanted access to
      more social contacts. Relatives and friends turned out to be the patient's main
      source of supportive contacts. More severe negative and positive symptoms were
      related to a worse social network. Support was found for an association between
      characteristics of the social network, such as satisfaction with social contacts,
      and quality of life. The results give reason to suggest that the care system
      should consider the informal caregivers' situation and focus on interventions,
      which enhance the patient's satisfaction with social contacts.

PMID- 11589338
TI  - Do measures of bronchial responsiveness add information in diagnosis and
      monitoring of patients with asthma?

PMID- 11589339
TI  - How infections can modify lung immunity.

PMID- 11589340
TI  - Markers of airway inflammation and airway hyperresponsiveness in patients with
      well-controlled asthma.
AB  - In steroid-naive asthmatics, airway hyperresponsiveness correlates with
      noninvasive markers of airway inflammation. Whether this is also true in steroid
      treated asthmatics, is unknown. In 31 stable asthmatics (mean age 45.4 yrs, range
      22-69; 17 females) taking a median dose of 1,000 microg inhaled corticosteroids
      (ICS) per day (range 100-3,600 microg x day(-1)), airway responsiveness to the
      "direct" agent histamine and to the "indirect" agent mannitol, lung function
      (forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak
      expiratory flow (PEF)), exhaled nitric oxide (eNO), and number of inflammatory
      cells in induced sputum as a percentage of total cell count were measured. Of the
      31 subjects, 16 were hyperresponsive to mannitol and 11 to histamine. The dose
      response ratio (DRR: % fall in FEV1/cumulative dose) to both challenge tests was
      correlated (r=0.59, p=0.0004). However, DRR for histamine and DRR for mannitol
      were not related to basic lung function, eNO, per cent sputum eosinophils and ICS
      dose. In addition, NO was not related to basic lung function and per cent sputum
      eosinophils. In clinically well-controlled asthmatics taking inhaled
      corticosteroids, there is no relationship between markers of airway inflammation
      (such as exhaled nitric oxide and sputum eosinophils) and airway responsiveness
      to either direct (histamine) or indirect (mannitol) challenge. Airway
      hyperresponsiveness in clinically well-controlled asthmatics appears to be
      independent of eosinophilic airway inflammation.

PMID- 11589341
TI  - Increasing prevalence of bronchial hyperresponsiveness in three selected areas in
      East Germany. Bitterfeld Study Group.
AB  - The prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergic
      rhinitis in children was lower in East Germany compared to West Germany. The
      reasons for this difference are still not understood. This study tested the
      hypothesis that prevalence of BHR increased in East German children after
      reunification. Two consecutive cross-sectional surveys of schoolchildren aged 8
      14 yrs from three communities in East Germany were carried out in 1992-1993 and
      1995-1996. A subsample of 530 and 790 children with complete lung function and
      cold air challenge data was analysed. The prevalence of BHR increased from 6.4%,
      in 1992-1993 to 11.6% in 1995-1996 (odds ratio (OR): 2.0, 95% confidence interval
      (CI): 1.3-3.0, adjusted for age, sex, season, community and parental education).
      No changes were found for asthma, allergic rhinitis or allergic sensitization. In
      contrast, physician diagnosed bronchitis, pneumonia and frequent colds decreased
      significantly. The observed increase in the prevalence of BHR was reduced (OR:
      1.5, 95% CI: 0.95-2.3) after adjustment for several indoor factors. In
      conclusion, while the prevalence of nonallergic respiratory diseases seems to
      decrease, the prevalence of bronchial hyperresponsiveness might be a first
      indicator of the suspected increase of asthma prevalence in East Germany. The
      present results give indirect evidence, that less respiratory infections may be
      associated with higher bronchial hyperresponsiveness.

PMID- 11589342
TI  - Symptoms of asthma, bronchial responsiveness and atopy in immigrants and
      emigrants in Europe. European Community Respiratory Health Survey.
AB  - Migration studies on asthma may provide information on its environmental causes.
      The European Community Respiratory Health Survey has potential advantages due to
      the number of countries involved, standardized collection of information,
      assessment of directionality of migration, and availability of physiological data
      on bronchial responsiveness and atopy. Prevalence rates of symptoms associated
      with asthma were compared for immigrants, emigrants and nonmigrants living in
      centres mostly in western Europe. Similar analyses were carried out for bronchial
      responsiveness (provocative concentration causing a 20% fall in forced expiratory
      volume in one second and slope) and atopy. Medication and use of health services
      were also explored. Overall, 1,678 (8.6%) of 19,516 participants were immigrants
      in the 18 countries participating in the study, of whom 581 were emigrants from
      one of the participating countries. Rates of asthma symptoms were higher in
      immigrants (odds ratio (OR): 1.21, 95% confidence interval (CI): 1.00-1.51) and
      emigrants (OR: 1.31, 95% CI: 0.96-1.51) compared to nonmigrants after controlling
      for area, sex, age and smoking status. However, bronchial responsiveness and
      atopy were equally distributed between immigrants, emigrants and nonmigrants. Use
      of health services was observed to be similar in migrants and nonmigrants with
      asthma. In the European Community Respiratory Health Survey, migrants reported
      more asthma symptoms, but had similar bronchial responsiveness, atopy, and use of
      health services when compared with the nonmigrant population.

PMID- 11589343
TI  - Expression of GATA family of transcription factors in T-cells, monocytes and
      bronchial biopsies.
AB  - GATA-binding proteins are a subfamily of zinc finger transcription factors with
      six members (GATA-1-6) that interact with the GATA deoxyribonucleic acid (DNA)
      sequence. This sequence is found in the regulatory regions of many genes
      including those encoding T-helper 2 (Th2)-like cytokines, receptors, adhesion
      molecules and enzymes, which may be important in the pathogenesis of bronchial
      asthma. The expression of GATA-3, 4 and -6 was investigated in peripheral blood T
      lymphocytes and monocytes and bronchial biopsies from 11 normal subjects and 10
      steroid-naive asthmatic patients. Using Western blot analysis, T-cells from
      asthmatic subjects expressed 5 times the level of GATA-3 compared to that in
      normals. Confocal microscopy indicated that GATA-3 expression was both nuclear
      and cytoplasmic. GATA DNA binding complex containing GATA-3 was elevated in Th2
      cells as determined by electrophorectic mobility shift assay. In contrast,
      monocytes from normal and asthmatic subjects expressed GATA-4 and -6 in equal
      amounts, but no GATA-3 was found. Using immunohistochemistry in bronchial
      biopsies, epithelial cells expressed high levels of GATA-3, GATA-4 and GATA-6
      proteins. Comparison of Western blots of bronchial biopsies showed no significant
      differences between normal and asthmatic subjects. In conclusion, the increased
      expression of GATA-3 in asthmatic T-cells may underlie augmented T-helper 2-like
      cytokines in this disease. However, the unaltered GATA-3 expression in epithelial
      cells suggests a distinct role for GATA-3 in these cells unrelated to T-helper 2
      like cytokine release. Finally, no evidence was found for an increased expression
      of GATA-4 and GATA-6 in asthma.

PMID- 11589344
TI  - Memory for symptoms in COPD patients: how accurate are their reports?
AB  - The purpose of this study was to examine the accuracy of self-reports of symptom
      intensity in patients with chronic obstructive pulmonary disease (COPD) and
      factors that might influence recall of that intensity. Thirty COPD (forced
      expiratory volume in one second (FEV1) 36 +/- 17% predicted) subjects recorded
      their dyspnoea and fatigue intensity scores on a 0-10 scale for 14 consecutive
      days. On the fourteenth day, subjects recalled their average, greatest and least
      symptom intensity for the previous 14 days. General cognitive function,
      spirometry, and oxygenation were also measured. No significant differences were
      found between actual and recalled scores for dyspnoea or fatigue. General
      cognitive function, measured by the Mini Mental State Exam, correlated with the
      greatest and least dyspnoea and average fatigue difference scores (recall-actual)
      and contributed to the variance in the average and least dyspnoea recalled
      scores. The greatest contributor to the variance in the recall scores of both
      symptoms was the symptom intensity level on the day of recall. These results
      highlight the importance of current levels of symptom intensity and cognitive
      function when appraising symptoms in chronic obstructive pulmonary disease
      patients.

PMID- 11589345
TI  - Surfactant protein gene A, B, and D marker alleles in chronic obstructive
      pulmonary disease of a Mexican population.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by chronic
      inflammation. It is most likely the result of complex interactions of
      environmental and genetic factors. Because pulmonary surfactant components play
      important roles in normal lung function, innate host defence, and inflammation in
      the lung, this study investigated the hypothesis that the surfactant protein
      genes are involved in certain cases of COPD. Genotype analysis of surfactant
      protein (SP)-A, SP-B, SP-B-linked microsatellite, and SP-D marker alleles was
      performed in patients with COPD (n=97) and smoker (n=82) or nonsmoker (n=99)
      controls. Univariate and multiple logistic regression analyses were performed.
      The regression analysis results between COPD and smokers revealed several COPD
      susceptibility alleles (AA62_A, B1580_C, D2S388_5), based on an odds ratio (OR
      >2.5). The predictive ability of this model for developing COPD is good
      (c=0.926). Allele-allele (B1580_C and D2S388_5) and allele-environment (i.e.
      smoking) interactions were detected. When smoker controls were compared to
      nonsmoker controls, marker D2S388 5 appeared to be smoking-independent (p=0.874),
      whereas marker alleles AA62_A (p=0.045) and B1580_5 (p=0.007) were smoking
      dependent. Males were at higher risk (OR=6.05, p=0.001), and smoking (>50 packs x
      yr(-1)) increased risk (OR=5.38, p=0.007). Males and alleles of loci flanking SP
      B were associated with more severe cases (forced expiratory volume in one
      second/forced vital capacity < or = 40%). The present results indicate that the
      surfactant protein alleles may be useful in chronic obstructive pulmonary disease
      by either predicting the disease in a subgroup and/or by identifying disease
      subgroups that may be used for therapeutic intervention. These observations
      should now be confirmed in a larger study, designed according to strict
      epidemiological criteria.

PMID- 11589346
TI  - Effects of PEEP on inspiratory resistance in mechanically ventilated COPD
      patients.
AB  - This study aimed to investigate the effect of increased lung volume with positive
      end-expiratory pressure (PEEP) on respiratory resistance in patients with chronic
      obstructive pulmonary disease (COPD). Ten patients with COPD were mechanically
      ventilated for acute respiratory failure. PEEP was set at 0, 5, 10 and 15 cm H2O.
      Using the rapid airway occlusion technique, the total inspiratory resistance of
      the respiratory system was partitioned into interrupter (Rint,rs) and additional
      effective (deltaRrs) resistances. At each level of PEEP, at constant inflation
      flow, the inflation volume (deltaV) was varied from 0.2-1 L, and, at constant
      deltaV, the inflation flow was varied from 0.2-1.2 L x s(-1). The changes in end
      expiratory lung volume (deltaEELV) induced by PEEP were also measured. The
      difference between the EELV and the relaxation volume of the respiratory system
      (deltaFRC) increased significantly with PEEP of 10 and 15 cm H2O as compared to a
      PEEP of 0, the increase being associated with a significant reduction of Rint,rs.
      By contrast, deltaRrs was independent of deltaFRC. At constant deltaV, Rint,rs
      fitted Rohrer's equation (Rint,rs = K1 + K2 x flow). While K2 significantly
      declined with AFRC, K1 did not change. At all levels of PEEP, deltaRrs was not
      influenced by deltaFRC. With increasing lung volume induced by positive end
      expiratory pressure, the inspiratory airway resistance decreased, whereas the
      viscoelastic behaviour of the respiratory system, as reflected by additional
      effective resistance, did not change.

PMID- 11589347
TI  - Sarcoidosis severity and socioeconomic status.
AB  - Several chronic diseases are more severe in persons who are Black, of low
      socioeconomic status (SES), and underinsured. The authors ask if this is true for
      sarcoidosis. Associations among sarcoidosis disease severity, SES, insurance
      coverage, and functional limitations were analysed. Back and White sarcoidosis
      patients (n=110) of a municipal and university hospital sarcoidosis registry were
      interviewed by telephone. Data on disease severity were abstracted from patient
      charts. Most patients reported good or excellent health by demographic
      characteristics. Low SES and no or public insurance were associated with worse
      health status and more severe dyspnoea. More advanced radiographic stage was
      associated with lower income, and forced vital capacity impairment with less
      education. Physical and social activity limitations due to physical and emotional
      disability were related to no or public insurance and lower income, but not
      education. Sarcoidosis severity is associated with socioeconomic status and
      insurance indicators; no or public insurance and low income are associated with
      functional limitations. Sarcoidosis-associated limitations are substantial,
      emphasizing the social significance of sarcoidosis. Lack of private insurance may
      inhibit the use of medical care, contributing to disease severity and impairment.

PMID- 11589349
TI  - Significance of lymphocytosis in bronchoalveolar lavage in suspected ocular
      sarcoidosis.
AB  - Ocular sarcoidosis is frequent in Japan, but in many cases the condition remains
      undiagnosed in patients with suspected ocular sarcoidosis. Bronchoalveolar lavage
      (BAL) was performed in order to study the clinical implications of lymphocytosis
      of BAL fluid in such patients with characteristic ocular manifestations. The
      subjects included in this study were 39 patients with suspected ocular
      sarcoidosis. The patients were divided into four types based on high-resolution
      computed tomography (HRCT) findings; no lung involvement (HRCT-0), bilateral
      hilar lymphadenopathy (BHL) without lung involvement (HRCT-I), lung involvement
      and BHL (HRCT-II), and lung involvement and no BHL (HRCT-III). Transbronchial
      lung biopsy (TBLB) and BAL were conducted after examining serum angiotensin
      converting enzyme and serum lysozyme values, skin test for purified protein
      derivative chest radiograph, HRCT, and gallium scintigram. Twenty patients were
      histologically diagnosed as having sarcoidosis, and 19 patients remained
      undiagnosed. Granuloma was identified by TBLB in 19 of 20 patients in type HRCT
      II but in only one of 19 patients in types HRCT-0 and HRCT-I (p<0.0001).
      Lymphocytosis in BAL (>15%) was identified in all patients who showed lung field
      involvement (type HRCT-II) and in 16 of 19 patients without lung field
      involvement (types HRCT-0 and HRCT-I). There were 10 patients whose only relevant
      findings were lymphocytosis in BAL. Among these 10 patients, an increased
      CD4+/CD8+ ratio (>3.5) in BAL was seen in 60%. The authors conclude that high
      resolution computed tomography results yield the same degree of diagnostic
      accuracy as transbronchial lung biopsy in ocular sarcoidosis suspects. However,
      bronchoalveolar lavage revealed significant lymphocytosis in patients with
      negative high-resolution computed tomography results. It should be kept in mind
      that a diagnostic group of patients with sarcoidosis who manifest ocular
      involvement and lymphocytosis in bronchoalveolar lavage exists.

PMID- 11589348
TI  - Serum Clara cell protein (CC16), a marker of the integrity of the air-blood
      barrier in sarcoidosis.
AB  - To test the hypothesis that sarcoidosis is associated with an intravascular
      leakage of lung epithelium secretory proteins, the occurrence and determinants in
      serum of sarcoid patients of CC16, a small size and readily diffusible lung
      specific protein of 16 kDa secreted by bronchiolar Clara cells, was investigated.
      CC16 was measured by a sensitive latex immunoassay in the serum of 117 patients
      with established sarcoidosis and of 117 healthy subjects matched for age, sex and
      smoking status. Stepwise regression analysis was used to identify extrapulmonary
      variables of CC16 changes in serum. These changes were then compared with
      biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF) as
      well as with the number of CC16 immunostaining cells on bronchial or pulmonary
      biopsy samples. CC16 concentration in serum of sarcoid patients was significantly
      increased, compared to their matched controls (25.9 +/- 16.2 versus 13.9 +/- 5.2
      microg x L(-1)). In nonsmoking patients without significant renal impairment,
      CC16 in serum increased with the severity of the chest radiograph and computed
      tomography changes, and was on average 50-100% higher when parenchymal
      involvement was present. Sarcoid patients had, however, normal levels of CC16 in
      BALF and an unchanged number of CC16-immunopositive cells in lung biopsy samples,
      suggesting that an increased secretion of CC16 in the sarcoid lung is very
      unlikely, and that the elevation of CC16 in sarcoidosis results from an increased
      intravascular leakage of the protein across the air-blood barrier. The present
      study suggests that CC16 in serum might provide a useful tool to noninvasively
      evaluate the damage and increased permeability to proteins of the air-blood
      barrier associated with sarcoidosis.

PMID- 11589350
TI  - Peripheral blood neutrophils are hyperresponsive to IL-8 and Gro-alpha in
      cryptogenic fibrosing alveolitis.
AB  - Cryptogenic fibrosing alveolitis (CFA) is characterized by increased pulmonary
      recruitment of peripheral blood neutrophils (PBNs) by interleukin (IL)-8 and
      other chemotactic mediators. This study investigated whether, in CFA, the PBN
      motility response is primed by IL-8 and growth-related oncogene (Gro)-alpha, as
      demonstrated in other neutrophilic inflammatory diseases, and whether the
      motility response of PBNs to IL-8 and Gro-alpha can be abrogated using a
      selective antagonist for the neutrophil receptor for IL-8 and Gro-alpha, CXCR2.
      The percentage of PBNs to undergo shape change (%SC), spontaneously and in
      response to IL-8 and Gro-alpha, was measured in patients with CFA (n=10) and
      controls (n=10), and the effect of the CXCR2 antagonist SB272844 studied. Plasma
      levels of IL-8, and Gro-alpha were measured using an enzyme-linked immunosorbent
      assay (ELISA). The %SC of unstimulated PBNs and the potency of Gro-alpha and IL-8
      to produce neutrophil polarization was greater in CFA than in controls; dose
      which produces 50% of maximal effect (EC50) of IL-8 was 3.6 +/- 0.7 nM for CFA
      versus 6.3 +/- 1.0 nM for controls; p<0.05. SB272844 inhibited Gro-alpha induced
      but not IL-8 induced neutrophil shape change (equilibrium constant (KD) 123 +/-
      18 nM). Plasma concentrations of Gro-alpha were increased in patients with CFA.
      PBNs are spontaneously activated and undergo a greater motility response to IL-8
      and Gro-alpha in CFA. Interleukin-8 and growth-related oncogene-alpha,
      circulating in substimulatory amounts in cryptogenic fibrosing alveolitis, may
      prime the peripheral blood neutrophils motility response, thus increasing their
      capacity for migration to the lung. Selective CXCR2 antagonists may be useful to
      block the Gro-alpha-induced priming response whilst preserving neutrophil
      functions mediated by CXCR1, the alternative neutrophil receptor for interleukin
      8.

PMID- 11589351
TI  - Influence of setting on unattended respiratory monitoring in the sleep
      apnoea/hypopnoea syndrome.
AB  - The high demand for full polysomnography and the better quality of sleep at home
      are the main reasons for performing home sleep studies. Home respiratory
      monitoring has been evaluated in several studies, but the influence of setting on
      the results of unattended respiratory monitoring has not been assessed to date.
      Unattended monitoring of respiratory variables at home and in the sleep
      laboratory was conducted in 35 consecutive patients with suspected sleep
      apnoea/hypopnoea syndrome. Respiratory variables during sleep, rate of successful
      studies and patient preference were compared. The data acquisition failure rate
      was 2.8% in the sleep laboratory and 5.7% at home. The mean difference between
      apnoea/hypopnoea indices (AHI) obtained from home and laboratory studies was 
      0.21 +/- 8 (95% confidence interval 3.27-2.84). Using the method comparison
      approach of Bland and Altman, the limits of agreement of the mean difference
      between AHI home and AHI laboratory were -16.7 and 17.1. No difference was
      observed between the studies in time spent in different body positions. When
      patients were asked where they would prefer to repeat the sleep study, 53%
      replied at home, 28% in hospital and 19% showed no preference. It was concluded
      that the setting of unattended respiratory monitoring (home or sleep laboratory)
      influences neither the number of valid studies nor the results of the respiratory
      parameters measured; most patients, however, preferred home studies.

PMID- 11589352
TI  - Efficacy of daytime continuous positive airway pressure titration in severe
      obstructive sleep apnoea.
AB  - The aim of this study was to evaluate manual nasal continuous positive airway
      pressure (nCPAP) titration during daytime polysomnography compared with
      conventional overnight titration for patients with severe obstructive sleep
      apnoea. Thirty-two patients who underwent daytime titration were retrospectively
      matched (for age, sex, body mass index and apnoea/hypopnoea index (AHI)) to a
      group titrated overnight during the same period. Successful titration was defined
      as the identification of the nCPAP level (effective nCPAP (Peff)) required to
      eliminate respiratory events during all sleep stages. After 3 months of therapy
      on nCPAP at Peff, nCPAP utilization history was obtained and a group of patients
      underwent a repeat polysomnogram (PSG) and completed a follow-up Epworth
      Sleepiness Scale (ESS) score. Initial titration was successful in 91% of daytime
      patients and 91% of overnight patients. The success of daytime titration was not
      related to diagnostic AHI or ESS score. Subjective nCPAP utilization was
      statistically similar in both groups. On the follow-up PSG, there were no
      significant differences between daytime (n=11) and overnight (n=11) patients in
      measures of sleep quality or respiratory disturbance. Both groups demonstrated
      similar and significant improvements in ESS score. These findings suggest that
      the effective nasal continuous positive airway pressure can be accurately
      established during daytime titration in a substantial proportion of severe,
      symptomatic obstructive sleep apnoea patients.

PMID- 11589353
TI  - Inflammatory mediators in nasal lavage, induced sputum and serum of employees
      with rheumatic and respiratory disorders.
AB  - Exposure to microbes present in mould-damaged buildings has been linked to
      increased frequency of various inflammatory diseases. The current study examined
      differences in inflammatory mediators in nasal lavage (NAL), induced sputum (IS)
      and serum of occupants with rheumatic or respiratory disorders and their
      controls, all working in the same moisture-damaged building. Exhaled nitric oxide
      (NO) measurements, lung function tests, skin-prick tests and health data
      collection by questionnaire were performed. Concentrations of NO, interleukin
      (IL)-1, IL-4, IL-6 and tumour necrosis factor-alpha in NAL, IS and serum
      (excluding NO and IL-1) of the subjects were measured during an occupational
      exposure period and the vacation period without such exposure. The concentrations
      of IL-4 in NAL fluid were significantly higher among all occupants during the
      working period (geometric mean 8.5 microg x mL(-1), range 0-206.5 microg x mL(
      1)), as compared to that during vacation (0.4 microng x mL(-1) range 0-3.7 pg x
      mL(-1)) (p = 0.008). Absence from the work environment also significantly
      diminished reporting of symptoms. IL-4 levels in the serum of case subjects were
      significantly higher than in controls. Moreover, employees with respiratory
      symptoms had markedly higher exhaled NO values than their controls (p = 0.028).
      In summary, these data suggest that mediators in nasal lavage samples reflect the
      occupational exposure to moulds, whereas possible indicators of existing
      disorders are detectable in serum.

PMID- 11589354
TI  - Changes in smoking habits and risk of asthma: a longitudinal population based
      study.
AB  - A common statement from exsmokers is that symptoms of asthma develop shortly
      after smoking cessation. This study, therefore, investigated the relationship
      between smoking cessation and development of asthma in a large cohort from the
      Copenhagen City Heart Study (CCHS). The CCHS is a longitudinal, epidemiological
      study of the general population from the capital of Denmark, conducted between
      1976 and 1994. The study population involved the 10,200 subjects who provided
      information on self-reported asthma and smoking habits from the first two
      examinations (baseline and 5-yr follow-up), and the 6,814 subjects who also
      attended the third and last examination (10-yr follow-up). The point-prevalence
      of smoking cessation as well as the asthma incidence between examinations was
      estimated, and a multivariate logistic regression model was used to examine the
      relationship between changes in smoking habits and development of asthma. During
      the study period, asthma incidence increased from 1.2-4.2%. Between examinations
      1,316 subjects quit smoking. Smoking cessation between examinations was
      significantly related to reported asthma at follow-up. With never-smokers as the
      reference group and following adjustment for sex, age, chronic bronchitis, level
      of forced expiratory volume in one second and pack-yrs of smoking, the odds ratio
      (OR) for developing asthma when quitting smoking between examinations was 3.9
      (95% confidence interval (CI) 1.8-8.2) from baseline to first follow-up and 3.1
      (95% CI 1.9-5.1) from first to second follow-up. Continuing smoking also
      increased the risk of asthma significantly (OR 2.6 and 2.0, respectively). The
      results indicate that exsmokers have a higher incidence of self-reported asthma
      than never-smokers. It is likely that subjects perceive chronic obstructive
      pulmonary disease as asthma, hence the relationship between smoking cessation and
      asthma might be due to misclassification rather than causality.

PMID- 11589355
TI  - Respiratory symptoms in relation to indoor exposure to mite and cat allergens and
      endotoxins. Indoor Factors and Genetics in Asthma (INGA) Study Group.
AB  - The authors investigated the relationship between respiratory symptoms in adults
      and exposure to mite and cat allergens, the role of endotoxins in house dust, the
      effects of mixtures of several allergens, and interactions between allergen
      exposure and allergic sensitization. Within a nested case-control study, 405
      subjects aged 25-50 yrs from two German cities answered a standardized
      questionnaire. Allergen-specific immunoglobulin-E was measured. Dust samples were
      taken from the subjects' homes to determine exposure to mite (Dermatophagoides
      pteronyssinus antigen 1 Der p 1) and (D. farinae antigen 1 Der f l) and cat (cat
      antigen d1 Fel d 1) allergen and endotoxin content in settled house dust.
      Exposure to Der f 1 and Der p 1 plus Der f 1 >10 microg x g(-1) of mattress dust,
      respectively, increased the risk of wheeze and breathlessness (odds ratios (OR):
      4.04, 95% confidence interval (CI): 1.53-10.64, OR: 2.78, 95% CI: 1.06-7.28). Fel
      d 1 >8 microg x g(-1) was positively associated with cough at night (OR: 2.74,
      95%, CI: 1.22-.17), noteworthy also in the nonsensitized subjects. Subjects
      exposed to elevated concentrations of more than one allergen had an up to seven
      fold increase in the risk of respiratory symptoms, compared to nonexposed
      subjects. Sensitized subjects exposed to elevated concentrations of Der f 1 or
      Fel d 1 were found to have the highest risk of asthma attacks and respiratory
      symptoms. No statistically significant association was found between exposure to
      endotoxins and respiratory health. Indoor exposure to Dermatophagoides farinae
      antigen 1 and cat antigen d1 is a risk factor for respiratory symptoms in adults,
      and for cat antigen d 1 even in nonsensitized subjects. The risk is increased if
      subjects are exposed to a mixture of allergens or if they are sensitized in
      addition to high exposure.

PMID- 11589356
TI  - Evaluation of impulse oscillation system: comparison with forced oscillation
      technique and body plethysmography.
AB  - The impulse oscillation system (IOS) has been developed recently to measure
      respiratory system resistance (Rrs) and reactance (Xrs) at different frequencies
      up to > or = 25 Hz. IOS has, however, not been validated against established
      techniques. This study compared IOS with the classical pseudorandom noise forced
      oscillation technique (FOT) and body plethysmographic airway resistance (Raw) in
      49 subjects with a variety of lung disorders and a wide range of Raw (0.10-1.28
      kPa x L(-1) x s). Rrs,IOS was slightly greater than Rrs,FOT, especially at lower
      frequencies, with a mean +/- SD difference at 5-6 Hz of 0.14 +/- 0.09 kPa x L(-1)
      x s. Comparisons with the wave-tube technique applied on two analogues indicated
      an overestimation by IOS. Xrs,IOS and Xrs,FOT were very similar, with a slightly
      higher resonant frequency with IOS than with FOT (mean difference +/- SD 1.35 +/-
      3.40 Hz). Raw was only moderately correlated with Rrn,FOT and Rrs-IOS; although
      the mean differences were small (0.04 +/- 0.14 kPa x L(-1)s for Rrs6,FOT and 
      0.10 +/- 0.14 kPa x L(-1) x s for Rrs5,IOS), IOS and FOT markedly underestimated
      high resistance values. In conclusion, the impulse oscillation system yields
      respiratory system resistance and reactance values similar, but not identical to
      those provided by the forced oscillation technique.

PMID- 11589357
TI  - Lung mucosal immunity: immunoglobulin-A revisited.
AB  - Mucosal defence mechanisms are critical in preventing colonization of the
      respiratory tract by pathogens and penetration of antigens through the epithelial
      barrier. Recent research has now illustrated the active contribution of the
      respiratory epithelium to the exclusion of microbes and particles, but also to
      the control of the inflammatory and immune responses in the airways and in the
      alveoli. Epithelial cells also mediate the active transport of polymeric
      immunoglobulin-A from the lamina propria to the airway lumen through the
      polymeric immunoglobulin receptor. The role of IgA in the defence of mucosal
      surfaces has now expanded from a limited role of scavenger of exogenous material
      to a broader protective function with potential applications in immunotherapy. In
      addition, the recent identification of receptors for IgA on the surface of blood
      leukocytes and alveolar macrophages provides an additional mechanism of
      interaction between the cellular and humoral immune systems at the level of the
      respiratory tract.

PMID- 11589358
TI  - Diagnostic strategies for suspected pulmonary embolism.
AB  - Pulmonary embolism often remains a difficult diagnosis for the clinician,
      particularly in patients with comorbidity factors. This is in contrast with the
      availability of effective treatment, which should be prescribed as soon as
      possible. To date, there is still no ideal diagnostic test that is accurate,
      safe, readily available and cost-effective. Recent technical advances in computed
      tomography, magnetic resonance imaging and laboratory findings have raised new
      possibilities in the diagnosis of pulmonary embolism. This review covers the
      performance of different diagnostic tests, and focuses on the advantages and
      limitations of single diagnostic tests and the clinical usefulness of these tests
      in diagnostic strategies.

PMID- 11589359
TI  - The European Community Respiratory Health Survey: what are the main results so
      far? European Community Respiratory Health Survey II.
AB  - The European Community Respiratory Health Survey (ECRHS) was the first study to
      assess the geographical variation in asthma and allergy in adults using the same
      instruments and definitions. The database of the ECRHS includes information from
      approximately 140,000 individuals from 22 countries. The aim of this review is to
      summarize the results of the ECRHS to date. The ECRHS has shown that there are
      large geographical differences in the prevalence of asthma, atopy and bronchial
      responsiveness, with high prevalence rates in English speaking countries and low
      prevalence rates in the Mediterranean region and Eastern Europe. Analyses of risk
      factors have highlighted the importance of occupational exposure for asthma in
      adulthood. The association between sensitization to individual allergens and
      bronchial responsiveness was strongest for indoor allergens (mite and cat).
      Analysis of treatment practices has confirmed that the treatment of asthma varies
      widely between countries and that asthma is often undertreated. In conclusion,
      the European Community Respiratory Health Survey has shown that the prevalence of
      asthma varies widely. The fact that the geographical pattern is consistent with
      the distribution of atopy and bronchial responsiveness supports the conclusion
      that the geographical variations in the prevalence of asthma are true and most
      likely due to environmental factors.

PMID- 11589360
TI  - Inflammatory endobronchial polyposis with bronchiectasis in cystic fibrosis.
AB  - An unusual case of endobronchial polyposis associated with extensive
      bronchiectasis in the context of cystic fibrosis (CF) has been described. A 15-yr
      old female patient with CF underwent partial pneumonectomy for extensive
      bronchiectasis and frequent infective pulmonary exacerbations. Cylindrical
      bronchiectasis with associated purulent bronchitis and bronchiolitis, together
      with inflammatory polyposis, was noted in the resected lung. To the best of the
      authors' knowledge, this is the first report of multiple endobronchial polyposis
      and may represent a rare complication of bronchiectasis in a patient with cystic
      fibrosis. On-going infection and the cellular composition of the polyps are
      discussed in relation to their possible aetiological relevance and relationship
      to upper respiratory tract polyps.

PMID- 11589361
TI  - Tolerable dietary lipid content that does not alter insulin secretion.
AB  - Lipids, either as membrane components or as fuel, are important nutrients that
      can affect insulin secretion. The aim of this study was to establish the maximum
      tolerable amount of fat present in the diet, which does not induce significant
      alteration in the process of insulin secretion. For that, just-weaned male albino
      rats (70-90 g body weight) were fed during 6 weeks with diets for growing rodents
      containing 7% fat (A Group) as recommended by the American Institute of Nutrition
      AIN. Two other groups in which the fat content of the diet was increased to reach
      10% (B Group) or 13% (C Group) were also included. Insulin release, 86Rb+ and
      45Ca2+ Fractional Outflow Rate (FOR) during the process of glucose-induced
      insulin secretion was determined in perfused islets isolated from these animals.
      No statistical differences in these parameters were detected between A and B
      rats. However, in the C group, a lower 86Rb+ FOR was found during the whole
      experiment and a poor insulin secretory response to glucose stimulus was
      observed. These results led us to postulate that the maximal limiting amount of
      total lipids present in the diet that does not impair the process of glucose
      induced insulin secretion is 10%. These findings authorize future studies on the
      interference of different dietary lipid sources, in a content 43% more elevated
      than that recommended (10% against 7%), on the mechanisms of insulin secretion.

PMID- 11589362
TI  - Enhanced absorption of 3-O-methyl-D-glucose through the small intestine of rats
      administered retinyl palmitate.
AB  - All-trans retinyl palmitate (RP) (1000 IU/kg body weight) was orally administered
      to rats for three days. The absorption of 3-O-methyl-D-glucose (3-OMG), which is
      actively transported by Na+-dependent D-glucose co-transporter (SGLT1), in the
      small intestine of the control and RP-treated rats was investigated by the in
      vito everted sac and in situ closed loop of intestine techniques. The absorption
      of [3H]3-OMG in both experiments of the in vito everted sac and in situ closed
      loop of intestine significantly increased in the RP-treated rats. AUC(0-120min)
      obtained from the [3H]3-OMG plasma concentration vs. time curve in the RP-treated
      rats was significantly larger than that in the control rats. On the other hand,
      the activity of Na+-K+-adenosinetriphosphatase (ATPase) and the transport rate of
      D-glucose mediated by Na+-independent facilitative glucose transporter (GLUT2) on
      the basolateral membrane (BLM) were similar between the control and RP-treated
      rats. Thus it is suggested that RP treatment of rats enhance the small intestinal
      absorption of glucose mediated by SGLT1.

PMID- 11589363
TI  - Effects of cysteine on the pharmacokinetics of intravenous adriamycin in rats
      with protein-calorie malnutrition.
AB  - In rats with protein-calorie malnutrition (PCM, 5% caseine diet for 4 weeks),
      hepatic cytochrome P450 levels suppressed markedly and cytochrome P450 mRNAs
      decreased significantly compared with those in control rats (23% caseine diet for
      4 weeks), however, the values completely (or partially) returned to control
      levels by a week (from fourth week) of cysteine supplementation (rats with PCMC)
      (Cho, Kim et al., Arch. Biochem. Biophys. 1999, 372: 150-158). The formation of
      aglycone metabolites of adriamycin and adriamycinol, M3 and M4, respectively,
      seemed to be induced (Lee and Lee, Res. Commun. Mol. Pathol. Pharmacol. 1999,
      105: 87-96) by pretreatment with dexamethasone (possibly by hepatic cytochrome
      P450 RL 33/cDEX, Komori and Oda, J. Biochem. 1994, 116: 114-120) in rats.
      Adriamycin, 16 mg/kg, was administered intravenously in 1-min to control rats and
      rats with PCM and PCMC. In rats with PCM, the plasma concentrations of adriamycin
      was higher (the area under the plasma concentration-time curve from time zero to
      12 hr, AUC(0-12 hr), tended to be higher) and 24-hr urinary excretion of M3
      (including its 'conjugates') seemed to increase than those in control rats,
      suggested that the formation of M3 was inhibited in rats with PCM. In rats with
      PCMC, the plasma concentrations of adriamycin were lower (the AUC(0-12 hr) was
      significantly smaller) and 24-hr urinary excretion of M3 (including its
      'conjugates') were significantly greater than those in rats with PCM, suggested
      that the formation of M3 increased significantly by cysteine supplementation by
      restoring the enzyme system(s) that metabolize adriamycin to M3. The altered
      pharmacokinetic parameters of adriamycin mentioned above in rats with PCM
      returned to greater than those of control rats after cysteine supplementation
      (rats with PCMC). Above data suggested that other hepatic cytochrome P450
      isozyme(s) which catalyze(s) the formation of M3 from adriamycin could be induced
      by cysteine supplementation.

PMID- 11589364
TI  - Anti-inflammatory effects of methotrexate on reversed passive Arthus reactions in
      rats.
AB  - The anti-inflammatory effects of methotrexate (MTX), an anti-rheumatic drug for
      treating rheumatoid arthritis, on acute inflammation were studied by using Arthus
      reactions induced in the pleural cavity and dorsal skin of rats. The effects were
      compared with those of dexamethasone (DEX), a synthetic analog of adrenocortical
      steroid, and of ketoprofen (KET), a nonsteroidal anti-inflammatory agent. In
      reversed passive Arthus (RPA) reactions induced in the pleural cavity by an anti
      bovine-albumin serum, DEX significantly suppressed both neutrophil accumulation
      and plasma exudation at the sites of injection of an antibody, whereas MTX and
      KET had no effect. In the RPA reaction induced in the dorsal skin by an anti
      ovalbumin serum, all three drugs inhibited exudation to the same level. However,
      DEX and MTX suppressed neutrophil accumulation, whereas KET did not. We found
      that the oral administration of MTX for 3 days significantly inhibited both
      neutrophil accumulation and exudation in the RPA reaction in the dorsal skin,
      suggesting that MTX is an effective anti-inflammatory agent. However, the
      manifestation of these anti-inflammatory effects might be restricted by
      differences in the inflammation models in rats.

PMID- 11589365
TI  - Proteasome inhibition suppresses cisplatin-dependent ERCC-1 mRNA expression in
      human ovarian tumor cells.
AB  - One of the major problems with ovarian cancer treatment is the clinical
      development of resistance to cisplatin. Considerable efforts have been directed
      toward the identification of biological and pharmacological agents that would
      reverse drug resistance to cisplatin. ALLnL is an inhibitor of the proteasome
      that can inhibit the ubiquitin-proteasome pathway, which plays an essential role
      in many processes in cell life. We have recently shown that ALLnL, at
      concentrations that do not appear harmful, has significantly enhanced DNA
      platination and decreased DNA repair of cisplatin-DNA adducts in human A2780/CP70
      ovarian carcinoma cells. These activities of proteasome inhibition were also
      associated with substantially increased cisplatin toxicity in these cells. In
      this communication, we demonstrate that treatment of A2780/CP70 cells with ALLnL
      blocks cisplatin-induced ERCC-1 mRNA expression in a concentration- and time
      dependent manner, as measured by Northern blot analysis. In addition, we showed
      that the cisplatin-dependent increase in steady-state levels of ERCC-1 mRNA was
      prevented by pretreatment with lactacystin, a potent and specific inhibitor of
      proteasome. These results suggest that the effect of proteasome inhibition on
      cisplatin cytotoxicity, DNA platination, and DNA repair of cisplatin adducts in
      ovarian cancer cells may be through down-regulating ERCC-1 expression.

PMID- 11589366
TI  - Tetrahydrobiopterin inhibits copper-induced oxidation of low density lipoprotein.
AB  - The effect of tetrahydrobiopterin (BPH4) on Cu2+-induced oxidation of low density
      lipoprotein (LDL) prepared from rabbit plasma was examined. BPH4 (0.5-10 microM)
      inhibited the formation of thiobarbituric acid-reactive substances (TBARS) in LDL
      induced by 5 microM Cu2+ in a dose-dependent manner. BPH4 also suppressed the
      increase in relative electrophoretic mobility (REM) of LDL in the presence of 5
      microM Cu2+. The potency of inhibitions of BPH4 on TBARS formation and REM was
      the same as or stronger than that of ascorbic acid and alpha-tocopherol, which
      are known as endogenous inhibitors of LDL oxidation. These results suggest that
      BPH4 could act as an efficacious endogenous inhibitor of atherogenic LDL
      modification.

PMID- 11589367
TI  - Interferon-gamma, tumor necrosis factor-alpha, and interleukin 1-beta suppress
      the replication of hepatitis B virus through oxidative stress.
AB  - The effect of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF
      alpha), interleukin 1-beta (IL-1beta), and H2O2, on hepatitis B virus (HBV)
      replication was analyzed in the HBV DNA transfected human hepatoblastoma-derived
      cell line HB 611. Secretion of HBV DNA from HB611 cells was inhibited by IFN
      gamma, TNF-alpha, IL-1beta, and H2O2 in a dose-dependent manner. These cytokines
      and H2O2 also decreased HBV mRNA expression in HB611 cells, meaning that these
      reagents decreased the synthesis of all virally encoded components of the HBV
      virion. The level of manganese-SOD mRNA, indicative of occurrence of oxidative
      stress, increased immediately after treatment with IFN-gamma, TNF-alpha, IL
      1beta, and H2O2. Moreover, the antioxidant N-acetyl-L-cysteine substantially
      inhibited the antiviral effect. Our findings suggest that oxidative stress may be
      a common factor in the antiviral effects of IFN-gamma, TNF-alpha, and IL-1beta on
      HBV.

PMID- 11589368
TI  - Pharmacokinetics, stability, and blood partition of 7-anilino-5,8
      isoquinolinedione, a new isoquinonlinedione derivative.
AB  - Pharmacokinetics of IQO4, a new isoquinolinedione derivative, after 30-min
      intravenous administration of the drug, 5 mg/kg, to rats, the stability, and the
      blood partition between plasma and blood cells of IQO4 were evaluated. After
      intravenous administration, IQO4 was eliminated fast with the mean total body
      clearance of 105 ml/min/kg. IQO4 was almost completely metabolized in rats; 5.18%
      of intravenous dose of IQO4 was excreted in 24-hr urine and IQO4 was under
      detection limit in whole gastrointestinal tract as 24 hr. IQO4 has a good
      affinity to liver, small intestine, heart, lung, and kidney as reflected to
      greater-than-unity tissue-to-plasma ratios. IQO4 was unstable in rat whole blood,
      plasma, and liver homogenates when incubated in a water-bath shaker for 24 hr
      kept at 37 degrees C and at a rate of 50 oscillations per min. The disappearance
      rate constants of IQO4 were 0.0611, 0.O436, and 0.174 hr(-1) for rat whole blood,
      plasma, and liver homogenates, respectively. However, IQO4 was stable for up to 3
      hr incubation in human gastric juices. The plasma-to-blood cell concentration
      ratios of IQO4 were independent of initial blood concentrations of IQO4, 0.5, 2,
      and 10 microg/ml, when the rabbit whole blood was incubated for up to 120 min;
      the ratios were in the range of 1.56-3.60. Since IQO4 was unstable in blood,
      considerable in vitro 'blood storage effect' in the plasma concentration of IQO4
      was observed.

PMID- 11589369
TI  - Structural chemistry and biological activities of natural products from Chinese
      herbal medicines--part II.

PMID- 11589370
TI  - Hemochromatosis: the irony of population screening.

PMID- 11589371
TI  - Long-term omeprazole treatment suppresses body weight gain and bone
      mineralization in young male rats.
AB  - BACKGROUND: The stomach is rich in endocrine cells, including those producing
      ghrelin, which is thought to play a role in the control of body growth.
      Omeprazole treatment is associated with hypergastrinaemia, resulting in growth of
      the oxyntic mucosa in general and the enterochromaffin-like (ECL) cells in
      particular. In the present study, we examined the effects of long-term omeprazole
      treatment on young male rats with respect to body growth and stomach. METHODS:
      Male rats (24 days old) were treated with omeprazole (400 micromol/kg/day) or
      vehicle for 77 days. The body weight was recorded twice per week. At sacrifice,
      dual-energy X-ray absorptiometry (DXA) was used to assess total bone area, bone
      mineral content (BMC), bone mineral density (BMD) and body composition (fat and
      lean body mass). The lengths of the spine and the femur were recorded. The plasma
      concentrations of gastrin and histamine were determined by radioimmunoassays. The
      endocrine cells of the stomach were examined by immunocytochemistry. RESULTS: The
      body weight gain was suppressed by omeprazole treatment. The bone area, BMC and
      BMD were reduced, while the lengths of the spine and the femur and the body
      composition were unchanged. Omeprazole-induced hypergastrinaemia was associated
      with enlargement of the oxyntic area and with hyperplasia of ECL cells but not of
      A-like cells and D cells. In contrast, the enterchromaffin (EC) cell density in
      the antrum was reduced. CONCLUSIONS: Omeprazole treatment of young male rats
      reduces body weight and bone mass gain. The densities of ECL cells in the oxyntic
      mucosa was increased and of the EC cells in the antral mucosa reduced.

PMID- 11589372
TI  - Morphological support for paracrine inhibition of gastric acid secretion by
      nitric oxide in humans.
AB  - BACKGROUND: Functional studies have shown that nitric oxide (NO) inhibits gastric
      acid secretion in a variety of species, including man. We have performed a
      morphological study with the intention of localizing the endothelial NO synthase
      (eNOS) in the human gastric mucosa. METHODS: Fifteen healthy subjects voluntarily
      participated in the study, and mucosal biopsies were obtained from the cardia,
      corpus and antrum. The presence and localization of eNOS were studied using
      immunohistochemical techniques. RESULTS: eNOS-immunoreactivity (eNOS-IR) is found
      in surface mucous cells of cardia, corpus and antrum. Unique to the oxyntic
      mucosa is the presence of eNOS-IR in 'endocrine-like' cells, found in close
      contact with parietal cells. CONCLUSIONS: eNOS-IR cells in close apposition to
      parietal cells provide morphological support for paracrine inhibition of gastric
      acid secretion by NO.

PMID- 11589374
TI  - Functional dyspepsia symptoms, gastric emptying and satiety provocative test:
      analysis of relationships.
AB  - BACKGROUND: The correlation between symptoms and observed impaired function in
      functional dyspepsia is still inconsistent. The aims of the study were to obtain
      a measure of satiety by a meal test; to verify whether this compares with
      severity of symptoms assessed using a reproducible questionnaire; and to
      correlate the parameters of satiety test and gastric emptying with all the
      dyspeptic symptoms. METHODS: Fifty-two functional dyspepsia patients reported
      their symptoms on a standardized questionnaire that considered belching,
      bloating, early satiety, epigastric pain and burning, nausea, postprandial
      fullness and vomiting. They were monitored for gastric emptying of a solid
      caloric meal using a radionuclide technique and underwent a test to quantify meal
      induced satiety by a liquid caloric meal. RESULTS: The number of kilocalories
      ingested during the satiety test until the occurrence of maximum satiety in
      healthy subjects was 110% higher than in the dyspeptic group (mean +/- s(mean):
      1110 +/- 23 versus 532 +/- 56; P < 0.01). We found a significant positive
      correlation between gastric emptying rate and kcal of the satiety test (P < 0.01;
      r = 0.428). Logistic regression showed a significant inverse association between
      severity of early satiety-coded as absent, mild, moderate or severe, kcal of meal
      test (P = 0.01), and gastric emptying lag phase (P = 0.03). Bloating was
      associated directly with t(1/2) of gastric emptying (P = 0.03) and inversely with
      lag phase (P = 0.02). CONCLUSIONS: The satiety test gives a fine numerical
      measure of satiety and confirms the results of a symptoms questionnaire. Our
      study showed an indirect correlation between severity of early satiety--as
      measured by the satiety test, and gastric emptying rate, as well as an
      association between bloating and delayed gastric emptying.

PMID- 11589373
TI  - Induction of chemokine and cytokine responses by Helicobacter pylori in human
      stomach explants.
AB  - BACKGROUND: The cytokine response during the acute phase of Helicobacter pylori
      infection in humans has not been studied. The aim of this study was therefore to
      investigate the early cytokine responses against H. pylori using cultured human
      stomach explants as a model of acute infection. METHODS: Gastric corpus tissue
      obtained from 13 adult uninfected and 3 H. pylori-infected patients undergoing
      gastric surgery due to obesity was used for preparation of mucosal explants. The
      cultured explants were exposed to different H. pylori strains or antigens, that
      is, lipopolysaccharides (LPS), urease and heat-shock protein (Hsp) B. The
      responses of the CXC chemokines interleukin (IL)-8, growth-related oncogene alpha
      (GROalpha) and interferon-inducible protein (IP) 10 as well as the CC chemokine
      regulated on activation normal T-cell expressed and secreted (RANTES) were
      determined by ELISA. In addition, IL-4, IL-6, IL-10, IL-12, interferon gamma
      (IFNgamma), tumour necrosis factor alpha (TNFalpha) and granulocyte-macropage
      colony stimulating factor (GM-CSF) were studied. RESULTS: In vitro H. pylori
      infection of the explants preferentially induced responses of the CXC chemokines
      GROalpha (P < 0.05) and IL-8 (P < 0.05), whereas the CC chemokine response
      (RANTES) was weak. In addition, the production of IL-6 was increased after H.
      pylori infection. Stimulation of the explants with different LPS preparations
      also induced strong GROalpha, IL-8 and IL-6 responses; the GROalpha responses
      being significantly higher after stimulation with rough than smooth H. pylori LPS
      (P < 0.05). CONCLUSIONS: GROalpha, IL-8 and IL-6 are increased early during acute
      H. pylori infection and may influence the development of gastric disease.

PMID- 11589375
TI  - Effect of a lacto-ovo vegetarian diet on fasting small intestinal motility.
AB  - BACKGROUND: Changes in diet can alter gastric and small intestinal (SI) motility.
      The effects of a vegetarian diet on fasting SI motility are unknown. METHODS:
      Manometric studies were performed in 9 lacto-ovo vegetarians (7 women) and 9
      omnivores (7 women) of similar age and body mass index. On each study day,
      manometry was used to assess SI motility for 5 h, or 3 complete cycles of the
      interdigestive motor complex (IDMC). Lacto-ovo vegetarians were studied once:
      omnivores were studied twice, on their usual diet, and after consuming a 14-day
      lacto-ovo vegetarian diet. Diet diaries were kept for 5 days prior to each
      manometric study. Data were analysed for dietary composition and for cycle length
      and duration of each phase (I, II and III) of the IDMC. RESULTS: Dietary intake
      did not differ between chronic vegetarians and chronic omnivores apart from a
      trend to higher fibre intake (29 +/- 3 versus 20 +/- 3 g/day; P = 0.058).
      Omnivores eating a vegetarian diet showed a trend to decreased alcohol
      consumption (P = 0.068), but did not increase their fibre intake (20 +/- 3 versus
      21 +/- 3 g/day). Neither cycle length nor duration of each IDMC phase differed
      between chronic vegetarians and chronic omnivores. After 14 days of a vegetarian
      diet, omnivores had a reduction in cycle length (128 +/- 19 versus 86 +/- 12 min;
      P = 0.02), with a non-significant reduction of Phase II (99 +/- 20 versus 50 +/-
      8 min: P = 0.066). CONCLUSIONS: A chronic vegetarian diet has no major effect on
      fasting SI motility; but acute dietary change may alter the cycle length and
      component phases of the IDMC.

PMID- 11589376
TI  - Gastric emptying of realistic meals with and without gluten in patients with
      coeliac disease. Effect of jejunal mucosal recovery.
AB  - BACKGROUND: Few data are available on disturbed gastric emptying in patients with
      coeliac disease. The aims of the study were to investigate (a) the presence of
      delayed gastric emptying: (b) the acute effect on gastric emptying of gliadin;
      and (c) the effect of jejunal recovery on gastric emptying of meals with or
      without gluten in such patients. METHODS: We measured gastric emptying of two
      meals in 16 patients with coeliac disease; one meal contained gliadin. Results
      were compared with those obtained in 24 controls. In 12 patients, both
      measurements were repeated after mucosal recovery. Statistical analysis was
      performed using the analysis of variance for repeated measurements and Student's
      t test. Mean +/- 1 s(mean) (standard error of the mean) are shown. RESULTS: No
      difference was found in fasting and in maximal antral sections after the two
      meals. On entry, gastric emptying was significantly (P < 0.001) delayed compared
      to controls both after the meal containing gluten (326.9 +/- 12.4 min versus
      controls 213.5 +/- 11.5) and after the gluten-free meal (315.3 +/- 16.7 min).
      After jejunal recovery, emptying of the meal containing gluten remained unchanged
      (337 +/- 18.9 min), whereas emptying of the gluten-free meal was significantly
      shortened (280.6 +/- 10.5 min; P < 0.001). CONCLUSIONS: In coeliac disease there
      is an impairment of gastric emptying which is at least partially reversible. This
      suggests either an immunological disorder or that unabsorbed meal constituents
      are responsible for an ileal-brake effect.

PMID- 11589377
TI  - Effect of glucagon, glicentin, glucagon-like peptide-1 and -2 on interdigestive
      gastroduodenal motility in dogs with a vagally denervated gastric pouch.
AB  - BACKGROUND: We previously reported that inhibition of gastric motility and
      hypertrophy of the small intestinal mucosa were observed after ileo-jejunal
      transposition which induced hypersecretion of enteroglucagon. Our aim was to
      study the effect of four enteroglucagon-related peptides (glucagon, glucagon-like
      peptide (GLP)-1, -2 and glicentin) on gastroduodenal motility and their
      mechanisms of action. METHODS: The effect of these four peptides on motilin
      induced interdigestive contractions was studied in dogs with vagally denervated
      gastric pouches equipped with four strain gauge force transducers on the pouch,
      gastric body, antrum and duodenum. Whether or not nitric oxide synthase inhibitor
      or phentolamine and propranolol reverses the inhibitory effect of those peptides
      was also studied. RESULTS: Glucagon inhibited contractions in the pouch and
      stomach but had no effect on duodenal contractility. GLP-1 inhibited contractions
      at all sites. GLP-2 inhibited contractions in the pouch but did not affect
      motility in the neurally intact gastroduodenum. Glicentin had no effect on
      contractions at any site. Pretreatment with either a nitric oxide synthase
      inhibitor or phentolamine and propranolol reversed the inhibitory effect of
      glucagon, GLP-1 and GLP-2 on contractions in the pouch, but did not alter the
      inhibitory effect of glucagon and GLP-1 on motility in the neurally intact
      stomach and duodenum. CONCLUSIONS: These results suggest that the effects of four
      peptides on gastroduodenal motility differ, and changes occur in the enteric
      neural modulation of motor activity after chronic surgical extrinsic denervation.

PMID- 11589378
TI  - Low faecal elastase 1 concentrations in type 2 diabetes mellitus.
AB  - BACKGROUND: Previous studies have suggested an association between impaired
      pancreatic exocrine function and diabetes, but the evidence is weak because the
      invasive nature of the tests used to define exocrine function has led to small
      studies on selected patients. The availability of faecal elastase 1 as a non
      invasive test has aided the detection of impaired exocrine function in population
      studies. We describe the association between levels of faecal elastase 1 and Type
      2 diabetes. METHODS: 544 Type 2 diabetic patients (age: 63 +/- 8 years) were
      randomly selected from local diabetes registers in Cambridgeshire, UK and
      individually matched for age, sex and practice to 544 controls in whom diabetes
      was excluded by HbA1c measurement. RESULTS: Faecal elastase 1 concentrations were
      significantly lower in cases than controls (median: cases 308 microg/g; controls
      418 microg/g; P < 0.01). Low levels of faecal elastase 1 (< 100 microg/g) were
      found in 11.9% of cases and 3.7% of controls (age-sex-adjusted odds ratio; 95%
      CI: 3.6; 2.2-6.2). After adjustment for potential confounding factors, the OR was
      4.5 (2.6-8.3). Among patients with diabetes, poor glycaemic control (HbA1c > or =
      7%) was associated with a higher risk of low elastase 1 level (OR 5.6; 1.5-37).
      No significant association was found with diabetes duration, peripheral
      neuropathy, alcohol intake, or prior gastrointestinal diseases. CONCLUSIONS:
      Faecal elastase 1 concentrations are lower in Type 2 diabetic patients than in
      non-diabetic controls, suggesting the co-existence of diabetes and impaired
      pancreatic exocrine function. Among the diabetic patients, the risk of having low
      elastase 1 levels was associated with glycaemic control.

PMID- 11589379
TI  - Topical and oral anti-inflammatory activity of budesonide compared with oral
      prednisolone in an animal model using allergen-induced gut mucosal exudation of
      plasma as a marker.
AB  - BACKGROUND: Development of topically active glucocorticosteroids with minimal
      systemic effects is paramount in improving therapy in inflammatory bowel disease.
      Our experimental model in the rat has proved useful for assessing topical versus
      systemic anti-inflammatory potency of glucocorticosteroids on the inflamed gut.
      METHODS: Experiments were performed on allergen-sensitized perfused rat ileum in
      vivo. Mucosal exudation of plasma, induced by local allergen perfusion, was
      measured as the appearance of circulating 125I-labelled albumin in the gut lumen.
      Experiments compared the anti-exudative effects of oral budesonide (0.1 mg/kg)
      with oral prednisolone (1, 3.3 or 10 mg/kg) and saline, given by oral gavage 24 h
      prior to allergen challenge, and of topical budesonide (3 x 10(-5) mol/L) with
      saline, administered in the perfusate 4 h prior to allergen challenge. Systemic
      glucocorticosteroid activity was assessed by weighing thymus glands after
      sacrifice. RESULTS: Allergen-induced plasma exudation was significantly reduced
      by oral budesonide, oral prednisolone (dose-dependently) and topically applied
      budesonide; topical budesonide was effective within 4 h. While prednisolone
      significantly reduced the relative thymus weight at both 3.3 and 10 mg/kg,
      budesonide given orally, 0.1 mg/kg, or topically, 3 x 10(-5) mol/L, had no
      significant effect. CONCLUSION: Budesonide, administered orally or topically,
      shows higher selectivity for the gut mucosa than prednisolone and produces local
      anti-inflammatory responses comparable to prednisolone, without the accompanying
      systemic effects.

PMID- 11589380
TI  - Dipeptidyl peptidase IV (DP IV, CD26) in patients with inflammatory bowel
      disease.
AB  - BACKGROUND: Dipeptidyl peptidase IV (DP IV, CD26), a serine protease with broad
      tissue distribution and known activity in serum, participates in T cell
      activation and promotes a Th1 cytokine response, a function in part attributable
      to its enzymatic activity. We hypothesized that the activity of DP IV in serum
      and expression of CD26/DP IV in lymphocytes may be altered in patients with
      inflammatory bowel disease (IBD). METHODS: Serum DP IV activity and CD26 (DP IV)
      positive peripheral blood lymphocytes were measured in 110 patients with IBD
      (Crohn disease (CD): n = 63, ulcerative colitis (UC): n = 47). Additionally, T
      cell activation antigens (CD25, CD95) and costimulatory molecules (CD28) were
      evaluated. The same analyses were carried out in healthy volunteers (HC, n = 28).
      Thirty-nine patients with CD and 28 patients with UC were reassessed 3-6 months
      after the first visit. RESULTS: In patients with IBD, the DP IV activity in serum
      was reduced (mean +/- s (standard deviation): 52.8 U/l +/- 16.9 (CD) and 55.7 +/-
      15.1 U/l (UC) versus 71.9 +/- 18.4 (HC), P < 0.001). Furthermore, patients with
      IBD had higher numbers of CD26-positive cells coexpressing CD25 and a higher
      surface expression of CD26 (DP IV) (mean fluorescence intensity, mean 57.1 (CD)
      and 59.8 (UC) versus 29.9 (HC), P < 0.001). The DP IV activity in serum showed an
      inverse correlation with known disease activity scores as well as with the
      concentrations of orosomucoid in serum. CONCLUSION: The changes of DP IV in
      patients with IBD highlight alterations at an interface between immune function
      and metabolism of peptide hormones, with potential importance for the
      pathophysiology of IBD. Furthermore, these changes may help to refine the
      assessment of IBD activity.

PMID- 11589381
TI  - Rectal nitric oxide assessment in children with Crohn disease and ulcerative
      colitis. Indicator of ileocaecal and colorectal affection.
AB  - BACKGROUND: Nitric oxide (NO) production is increased in inflammatory bowel
      disease (IBD). Measurements of luminal NO in Crohn disease and ulcerative colitis
      have revealed that levels are increased during active disease. We aim to evaluate
      whether rectal measurements of NO can reveal active disease of the colon as well
      as ileum. METHODS: Sixteen children with active Crohn disease in the ileocaecal
      or colorectal regions of the gut and 6 children with active ulcerative colitis
      were compared to a group of 14 healthy children. Gaseous samples for analysis of
      luminal NO were collected using a Foley catheter inserted into rectum. The
      balloon of the catheter was filled with NO-free air and incubated for 10 min.
      After aspiration, samples were analysed using chemiluminescence. Values are
      expressed as median and range. RESULTS: In healthy children, rectal NO values
      were 60 (0-275) ppb. In children with Crohn disease of the colorectal region, NO
      concentrations were 5,675 (300-49,350) ppb (P < 0.001), while those with Crohn
      disease of the ileocaecal region had NO levels of 2,625 (300-15,000) ppb (P <
      0.01). In children with ulcerative colitis, NO values of 5,500 (950-34,000) ppb
      were found (P < 0.001). CONCLUSION: Rectal NO levels are greatly increased in
      children with IBD. Highest values were found in patients with colorectal
      engagement, but rectal NO was increased also in ileocaecal disease. Rectal
      sampling of luminal NO is a simple and minimally invasive method and should be
      considered a diagnostic tool for intestinal inflammatory activity in children
      regardless of primary disease location.

PMID- 11589382
TI  - Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in
      patients with adult-onset idiopathic bile acid malabsorption.
AB  - BACKGROUND: A congenital form of idiopathic intestinal bile acid malabsorption
      (IBAM) has been associated with dysfunctional mutations in the ileal apical
      sodium-dependent bile acid transporter (ASBT). The aim of this study was to
      determine whether mutations in the ASBT gene (SLC10A2) predispose to the
      development of adult-onset idiopathic bile acid malabsorption and chronic watery
      diarrhea. METHODS: Genomic DNA was obtained from 13 adult IBAM patients
      previously diagnosed on the basis of clinical data, response to cholestyramine,
      and abnormal 75Se-homocholic acid taurine (SeHCAT) test values. The ASBT gene was
      screened for the presence of mutations or polymorphisms by single-stranded
      conformation polymorphism analysis (SSCP) and DNA sequencing. RESULTS: ASBT gene
      polymorphisms were detected in 5 of the 13 adult IBAM patients. Four patients
      were heterozygous for a common polymorphism in exon 3, leading to an alanine to
      serine substitution at codon 171 (A171S). An additional subject was heterozygous
      for a polymorphism in exon 1 that causes a valine to isoleucine substitution at
      codon 98 (V981). These functional polymorphisms were also found in unaffected
      subjects and do not appear to affect ASBT function. CONCLUSIONS: Adult-onset IBAM
      is not directly related to dysfunctional mutations in the coding region or
      intron/exon junctions of the SLC10A2 gene. In the absence of apparent ileal
      disease or intestinal motility defects, inappropriate down-regulation of the
      ileal bile acid transporter or defects in ileocyte transfer of bile acids into
      the portal circulation could explain this form of adult IBAM.

PMID- 11589383
TI  - Recombinant activated factor VII (rFVIIa) acutely normalizes prothrombin time in
      patients with cirrhosis during bleeding from oesophageal varices.
AB  - BACKGROUND: Patients with cirrhosis have low levels of coagulation factors, the
      most pronounced deficiency being that of FVII. This may compromise haemostasis
      during bleeding from ruptured oesophageal varices. The objective of this trial
      was to evaluate the effect of rFVIIa on prothrombin time in cirrhosis patients
      with ongoing variceal bleeding. Safety, including signs of DIC, was monitored.
      METHODS: The study is a single centre, open-label trial. Ten consecutive patients
      with known alcoholic cirrhosis and oesophageal variceal bleeding were included.
      The patients received routine treatment, including Terlipressin. Each patient
      received one i.v. injection of rFVIIa (80 microg/kg bw). The study observation
      time was 12 h per patient. RESULTS: The mean age of the patients was 48 years (8
      men and 2 women). The cirrhosis was classified as Child B in 5 patients and Child
      C in 5. At baseline, all patients had prothrombin time levels above the normal
      range, and all but one had FVII coagulation activity (FVII:C) levels below the
      normal range. rFVIIa normalized the prothrombin time in all patients within 30
      min. The effect lasted for more than 4 h in 7 patients, and for about 2 h in the
      remaining 3 patients. Immediate bleeding control was obtained in all patients,
      and no patient died within the study time. There was no sign of DIC. CONCLUSIONS:
      rFVIIa is effective in transiently reversing the prolonged prothrombin time in
      cirrhosis patients with haematemesis from varices. This indicates a potential of
      improving haemostasis and survival in patients with compromised coagulation due
      to liver disease.

PMID- 11589384
TI  - Effect of circulating peptide YY on gallbladder emptying in humans.
AB  - BACKGROUND: To further establish its role in the ileal brake mechanism, we
      determined the effect of the distal gut hormone peptide YY (PYY) on gallbladder
      motility and plasma gut hormones during the cephalic phase of meal stimulation.
      METHODS: Eight healthy volunteers were studied in a randomized crossover design,
      with or without intravenous infusion of a physiological dose of PYY. On each
      occasion, subjects underwent modified sham feeding followed by real feeding.
      RESULTS: PYY reduced gallbladder emptying in response to modified sham feeding
      from 23 +/- 5% to 5 +/- 7% (P < 0.01) and integrated plasma pancreatic
      polypeptide from 2337 +/- 397 pmol/L x 90 min to 903 +/- 232 pmol/L x 90 min (P <
      0.01). PYY enhanced plasma cholecystokinin in response to real feeding from 53 +/
      9 pmol/L x 90 min to 82 +/- 17 pmol/L x 90 min (P < 0.05), but did not
      significantly affect maximum gallbladder emptying and tended to decrease plasma
      pancreatic polypeptide. CONCLUSION: Circulating PYY suppresses the cephalic phase
      of postprandial gallbladder emptying, but not meal stimulated maximum emptying.
      The results support the hypothesis that the effect of PYY on gallbladder emptying
      is mediated by vagal-dependent rather than cholecystokinin-dependent pathways.

PMID- 11589385
TI  - Fecal elastase-1 determination: 'gold standard' of indirect pancreatic function
      tests?
AB  - BACKGROUND: Tubeless pancreatic function tests measuring the content of elastase
      1 and the activity of chymotrypsin in stool are used with different cut-off
      levels and with varying success in diagnosing functional impairment of the
      pancreas. The aim of our study was to re-evaluate the sensitivity and specificity
      of elastase-1 and chymotrypsin in stool in the assessment of exocrine pancreatic
      insufficiency. METHODS: In 127 patients displaying clinical signs of
      malassimilation, the secretin-caerulein test ('gold standard'), fecal fat
      analysis, fecal chymotrypsin activity and fecal elastase-1 concentration were
      performed. Exocrine pancreatic insufficiency was graded, according to the results
      of the secretin-caerulein test, into mild, moderate and severe. Chymotrypsin and
      elastase-1 in stool were estimated using two commercially available test kits.
      Fecal elastase-1 concentration of 200 and 100 microg/g stool and chymotrypsin
      activity of 6 and 3 U/g stool were used separately as cut-off levels for
      calculation. RESULTS: 1) In 65 patients, a normal pancreatic function was found
      using the secretin-caerulein test. In 62 patients, an exocrine pancreatic
      insufficiency was found and classified into severe (n = 25), moderate (n = 14)
      and mild (n = 23). 2) The correlation between fecal elastase-1 and chymotrypsin
      with duodenal enzyme outputs of amylase, lipase, trypsin, chymotrypsin and
      elastase-1 ranged between 33% and 55% and 25% and 38%, respectively. 3) Using a
      cut-off of 200 microg elastase-1/g, stool sensitivities of fecal elastase-1 and
      fecal chymotrypsin (cut-off: 6 U/g) were 100% and 76%, respectively (P < 0.0001
      and P < 0.001 respectively) in severe exocrine pancreatic insufficiency, 89% and
      47% respectively (P < 0.001; P = 0.34, respectively) in moderate and 65% for both
      in mild pancreatic insufficiency. Specificities of elastase-1 and chymotrypsin in
      stool were 55% and 47%, respectively. 4) Elastase-1 based diagnostic provided a
      positive predictive value of 50% using a cut-off' 200 microg/g stool in a
      representative group of consecutively recruited patients with gastroenterological
      disorders. CONCLUSION: Determination of fecal elastase-1 is highly sensitive in
      the diagnosis of severe and moderate exocrine pancreatic insufficiency and is of
      significantly higher sensitivity than fecal chymotrypsin estimation. Specificity
      for both stool tests is low. Correlation between elastase-1 and chymotrypsin in
      stool and duodenal enzyme outputs is moderate. Neither test is suitable for
      screening, as they provide a pathologic result in roughly half of 'non-pancreas'
      patients.

PMID- 11589387
TI  - Screening for hemochromatosis: high prevalence and low morbidity in an unselected
      population of 65,238 persons.
AB  - BACKGROUND: Hereditary hemochromatosis (HH) is a common genetic disease leading
      to accumulation of iron in several organs, most notably the liver. The
      C282Y/C282Y mutation in the HFE gene is found in most cases. In order to prevent
      clinical disease and to study the cost and feasibility of screening, a large
      population was screened. METHODS: In a Norwegian county, all inhabitants 20 years
      or older were invited to participate in a population-based health survey
      programme. Screening for HH was one of several subprojects. Blood samples were
      obtained from 65,238 persons. Subjects with high serum transferrin saturation in
      two tests and high serum ferritin were clinically evaluated for HH. All subjects
      with high serum transferrin saturation in two tests were offered genotyping.
      RESULTS: HH was newly diagnosed in 92 women and 177 men. Phlebotomy treatment was
      performed in 64 women and 152 men. Severe organ damage (liver cirrhosis) was
      ascertained in only 4 men. We found no correlation between serum ferritin and
      age. The estimated cost was US$ 1.6 per subject screened and US$ 390 per newly
      discovered HH subject. The estimated prevalence of phenotypical HH not previously
      known was 0.34% in women and 0.68% in men. The prevalence of the C282Y/C282Y
      mutation was at least 0.68%. CONCLUSION: Large-scale screening for HH can be
      performed at a relatively low cost if combined with a health survey programme.
      The yield in terms of newly discovered cases is considerable, but few cases were
      found seriously ill. Better knowledge of the natural course of HH is necessary if
      we are to be able to estimate the cost-effectiveness of large-scale screening.

PMID- 11589386
TI  - Cellular markers of systemic inflammation and immune suppression in patients with
      organ failure due to severe acute pancreatitis.
AB  - BACKGROUND: Few data are available on cellular markers of systemic inflammation
      and immune suppression in early acute pancreatitis. The aim of this study was to
      describe the cellular immune inflammatory status of patients with acute
      pancreatitis in relation to development of organ failure. METHODS: Prospective
      study including 89 patients who presented within 72 h of onset of pain. Fifty
      eight of them had mild disease (Grade I group), 19 had severe disease with no
      organ dysfunction (Grade II group) and 12 had severe disease with organ
      dysfunction (Grade III group). Serial blood samples were collected on admission
      and following 2 days. Phagocyte surface markers were analysed using flow
      cytometry. RESULTS: The proportion of HLA-DR-positive monocytes, a marker of
      immune suppression, and CD11b expression level on neutrophils and monocytes, a
      marker of systemic inflammation, were related to Grades I-III (P for trend
      <0.001). In Grade III patients, the proportion of HLA-DR-positive monocytes was
      low on presentation, or decreased rapidly during follow-up, whereas CD11b
      expression levels were persistently high. L-selectin and monocyte CD14 expression
      levels were not related to disease severity. CONCLUSIONS: Immune suppression
      develops early, rapidly and unexpectedly in patients with acute pancreatitis.
      Monitoring immune inflammatory status may provide the means by which to identify
      patients who benefit from biological response modifier therapy.

PMID- 11589389
TI  - An attempt at Helicobacter pylori eradication with intravenous clarithromycin in
      perforated peptic ulcer patients.

PMID- 11589388
TI  - Malignancy in slow motion: diagnosis of biochemically apparent, but otherwise
      occult persistent disease 21 years after resection of a carcinoid tumour of the
      terminal ileum.
AB  - Carcinoid tumors may relapse after a long time span following initial diagnosis,
      and relapse might be clinically inapparent despite biochemical indications due to
      a low sensitivity of conventional methods. We present the case of a patient who
      had biochemical indication for hidden disease persistence for more than two
      decades. In 1978, a 39-year-old man underwent surgery for a carcinoid tumour of
      the ileum measuring 3.5 cm with multiple local lymph-node metastases. After
      surgery, however, serotonin- and urinary 5-hydroxy-indole-acetic-acid (5-HIAA)
      remained markedly elevated, and persisted over more than 20 years at levels
      between 600 and 950 ng/ml for serum serotonin (normal range 40-400 ng/ml) and 29
      35 mg/24 h for 5-HIAA (normal range 2-9 mg/24 h). Despite this, regular
      radiological follow-up, including sonography and CT-scan, did not reveal the
      location of suspected malignancy until 1999, when the patient was re-admitted to
      our hospital for a hypertensive episode. CT-scanning of the abdomen showed a
      singular lesion within the liver, which was verified as recurrence of the
      carcinoid by fine needle biopsy. Somatostatin receptor scintigraphy using (111)In
      DTPA-D-Phe1-Octreotide revealed a second lesion within the liver along with local
      recurrence at the anastomosis, which was verified by surgery. While the
      propensity for late relapse of ileal carcinoids has repeatedly been demonstrated,
      a case with biochemical signs of disease persistence over a time span of 21 years
      before final diagnosis is unusual. In addition, our case reflects the low
      sensitivity of conventional radiological evaluation for localization of carcinoid
      tumours as compared to somatostatin receptor scanning.

PMID- 11589390
TI  - The biogeochemical cycling of carbon dioxide in the oceans--perturbations by man.
AB  - The purpose of the paper is to follow up the contribution by Dyrssen and Turner
      to the Hemavan meeting in 1993 on CO2 chemistry. Machta's treatment from 1971 of
      the role of oceans and biosphere in the carbon dioxide cycle is reviewed. Using
      data on the emission of CO2 and the atmospheric content in addition to the value
      recently presented by Takahashi et al. for the net sink for global oceans the
      following numbers have been calculated for the period 1990 to 2000, annual
      emission of CO2, 6.185 PgC (Petagram = 10(15) g). Annual atmospheric
      accumulation, 2.930 PgC. Annual sinks, 3.255 PgC. Net uptake for 1990 by the
      oceans, 1.151 PgC/year. Solubility pump into the mixed layer, 0.828 PgC/year.
      Residual input (e.g. riverborne), 0.323 PgC/year. Annual uptake by land
      phytomass, 2.104 PgC. In addition, perturbations involving irrigation and
      fertilization, limestone dissolution, iron and clathrate addition are mentioned.

PMID- 11589391
TI  - The chemistry of Norwegian groundwaters: IV. The pH-dependence of element
      concentrations in crystalline bedrock groundwaters.
AB  - A total of 1604 samples of crystalline bedrock groundwaters in Norway have been
      analysed for pH, major and minor elements. A subset of 476 samples were also
      analysed for a wide range of trace elements by ICP-MS. The pH of the samples
      ranges from 5.4 to 9.8, with a predominance of pH values between 8.0 and 8.2. The
      data-set is divided into five 20-percentile groups according to increasing pH.
      The concentrations of 60 elements are then displayed as box-plots for each pH
      group. A line through the five medians yields a visual demonstration of the
      relationship with, and sensitivity to, pH variations for concentrations of each
      element. Twelve characteristic trends are distinguishable, from which some of the
      main hydrogeochemical processes related to pH and groundwater evolution can be
      inferred.

PMID- 11589392
TI  - Partitioning of copper onto suspended particulate matter in river waters.
AB  - Suspended particles and river water from the Susquehanna River, White Clay Creek
      and the Delaware River were collected to experimentally study the partitioning of
      copper. The effects of many factors that may influence the partitioning
      coefficient (Kd) including pH, total suspended solids (TSS), total copper
      concentration ([Cu]T), dissolved organic matter (DOM), particulate organic matter
      (POM), hardness, and ionic strength were investigated by performing batch
      adsorption experiments. The results implied that organic matter binding sites in
      both the aqueous and solid phases play the most important role in controlling
      copper partitioning. Other major factors governing the partitioning are pH and
      TSS. Kd increases with pH in the pH range 3-8. TSS increases caused decreases in
      Kd values, which may be attributed to the decrease in the quantity of available
      binding sites caused by interparticle interactions, rather than by the
      redistribution of organic matter between solid and solution phases with the
      variation of TSS. Kd decreases slightly when total Cu concentration increases;
      however, Kd can be considered to be independent of Cu concentration when TSS is
      high. The effects of calcium competition and ionic strength on partitioning are
      small.

PMID- 11589393
TI  - Risk of arsenic transfer to a semi-confined aquifer and the effect of water level
      fluctuation in North Mortagne, France at a former industrial site.
AB  - Groundwater contamination by arsenic was studied in the area of a former larger
      zinc refinery in France. Maximum contamination was observed under the former
      sulfuric acid factory, while the overall waste storage area was less
      contaminated. Arsenic concentrations there were controlled by the solubility of
      3:2 calcium arsenate mineral Ca3(AsO4)2 (s) and probably a gypsum/calcium
      arsenate CaSO4 (s)/Ca3(AsO4)2 (s) solid solution. The speciation of As below the
      former sulfuric acid factory indicates an overall predominance of As(III)
      species. The sorption by the clay aquitard was complete for As(V), but limited to
      approximately 30% for As(III) under our experimental conditions. A potential risk
      exists, although very limited in area, of contamination of the underlying sandy
      aquifer and drinking water wells.

PMID- 11589394
TI  - Specific detection of cyclobutane pyrimidine dimers in phytoplankton DNA by a non
      radioactive assay based on T4-endonuclease V digestion.
AB  - The effect of artificial and natural UV irradiation on DNA in marine
      phytoplankton Isochrysis galbana monoculture was investigated. The presence of
      cyclobutane pyrimidine dimers (CPDs) in unlabelled I. galbana DNA was detected by
      a non-radiometric alkaline filter elution assay after T4-endonuclease V
      digestion. The quantity of CPDs was estimated by alkaline agarose gel
      electrophoresis. Precise determination of the amount of DNA in the presence of I.
      galbana pigments was achieved by oxazole yellow homodimer (YOYO) dye. T4
      endonuclease V-sensitive sites frequency (ESS/kb), measured after exposure to 2
      40 kJ m(-2) of artificial UV light, increased in a dose-dependent manner. Twelve
      hours after irradiation cell culture growth was disrupted, and 50% of initial DNA
      damage in the cells was observed. After 1 h of sunlight exposure, the incidence
      of CPDs increase significantly. Prolonged exposition to sunlight decrease CPDs
      incidence due to efficiency of I. galbana DNA repair mechanisms. The presence of
      water-soluble crude oil fraction (WSOF) affected DNA repair efficiency resulting
      in accumulation of CPDs in I. galbana DNA.

PMID- 11589395
TI  - Study on CO2 global recycling system.
AB  - In order to assist in finding ways to mitigate CO2 emission and to slow the
      depletion of fossil fuels we have established and evaluated a representative
      system, which consists of three technologies developed in our laboratory. These
      technologies were in CO2 recovery, hydrogen production and methanol synthesis and
      in addition we established the necessary supporting systems. Analysis of outline
      designs of the large scale renewable energy power generation system and this
      system and energy input for building plant, energy input for running plant has
      been conducted based on a case using this system for a 1000-MW coal fired power
      plant, followed by an evaluation of the material balance and energy balance. The
      results are as follows. Energy efficiency is 34%, the CO2 reduction rate is 41%,
      the balance ratio of the energy and CO2 of the system is 2.2 and 1.8,
      respectively, on the assumption that the primary renewable energy is solar
      thermal power generation, the stationary CO2 emission source is a coal-fired
      power plant and the generation efficiency of the methanol power plant is 60%. By
      adopting the system, 3.7 million tons of CO2 can be recovered, approximately 2.7
      million tons of methanol can be produced, and 15.4 billion kWh of electricity can
      be generated per year. Compared to generating all electrical power using only
      coal, approximately 2.6 million tons of coal per year can be saved and
      approximately 2.15 million tons of CO2 emission can be reduced. Therefore, it is
      clearly revealed that this system would be effective to reduce CO2 emissions and
      to utilize renewable energy.

PMID- 11589396
TI  - Blood lead and its effect on Cd, Cu, Zn, Fe and hemoglobin levels of children.
AB  - The levels of heavy metals, such as Pb, Cd, Cu, Zn and Fe, in whole blood samples
      of Mumbai and Hyderabad children have been determined. In the present study, 576
      blood samples of children (3-6 years old) were collected during 1996-1998 and
      analyzed for heavy metal contents by anodic stripping voltammetry and atomic
      absorption spectrometry. The geometric mean concentrations of Pb, Cd, Cu and Zn
      in blood of Mumbai children were 8.0, 0.10, 86.5 and 398.9 microg dl(-1), while
      those for Hyderabad children were 13.3, 0.13, 100.6 and 483.4 microg dl(-1)
      respectively. The geometric mean concentrations of Fe in the blood of Mumbai and
      Hyderabad children were 21.9 and 34.5 mg dl(-1), respectively. Of the Mumbai
      children, 61.8% were found to have a blood lead concentration lcss than 10 microg
      dl(-1), while the corresponding proportion of Hyderabad children was 27.4%.
      Higher concentrations of Pb in the children's blood were observed at high traffic
      areas in both cities. A decreasing trend in the hemoglobin content with
      increasing blood lead levels was observed for Mumbai children. A good negative
      correlation (-0.61) between the blood lead and iron has been observed for Mumbai
      children The hemoglobin content of 85% of the study population was found to vary
      between 8 and 14 g%.

PMID- 11589397
TI  - Runoff rates and ecotoxicity of zinc induced by atmospheric corrosion.
AB  - Initiated by regulatory restrictions on the use of zinc for various building and
      construction applications, together with a lack of knowledge related to the
      release of zinc induced by atmospheric corrosion, a major interdisciplinary
      research project was implemented to generate data to be used in future risk
      assessment. Runoff rates from a large number of commercially available zinc-based
      materials have been determined on panels inclined 45 degrees from the horizon,
      facing south, during a 1-year atmospheric exposure in an urban environment in
      Sweden. Possible environmental effects of runoff water immediately after leaving
      the surface of the various materials have been evaluated during two different
      sampling periods of varying season and zinc concentration, using the standard
      growth inhibition test with algae. Raphidocelis subcapitata (formerly Selenastrum
      capricornutum). Zinc-specific biosensors with the bacterial strain of Alcaligenes
      eutrophus, and computer modeling using the water-ligand model MINTEQA2 and the
      humic aquatic model WHAM, have been used to assess the bioavailability and
      chemical speciation of zinc in the runoff water. An excellent consistency between
      the different methods was observed. The results show considerably lower runoff
      rates of zinc (0.07-3.5 g m(-2) year(-1)) than previously being used for
      regulatory restrictions, and the concentration of zinc to be predominantly
      responsible for the observed toxicity of the runoff water towards the green
      algae. The majority of the released zinc quantity was found to be present as free
      hydrated zinc ions and, hence, bioavailable. The data do not consider changes in
      bioavailability and chemical speciation or dilution effects during entry into the
      environment, and should therefore only be used as an initial assessment of the
      potential environmental effect of zinc runoff from building applications. This
      interdisciplinary approach has the potential for studies on the environmental
      fate of zinc in soil or aquatic systems.

PMID- 11589398
TI  - Determination of polychlorinated biphenyls in Antarctic macroalgae Desmarestia
      sp.
AB  - Selected polychlorinated biphenyl (PCB) congeners were measured in Desmarestia
      sp., an abundant algae in the Antarctica Peninsula and South Shetlands. Samples
      were collected from various points of Admiralty Bay, King George Island,
      Antarctic Peninsula, during the 1993-1994 austral summer. Total PCB
      concentrations ranged from 0.46 to 3.86 ng g(-1) (dry weight). Predominant PCB
      congeners were 52, 101, 110, 138 and 153. The low levels of PCBs found on all
      samples and the predominance of low molecular weight congeners indicate that
      there are no significant local PCBs sources in the area of study.

PMID- 11589399
TI  - Persistent organic pollutants in agricultural soils of central Germany.
AB  - Concentrations of persistent organic pollutants (HCHs, DDX, PCBs and HCB) were
      measured in topsoils from 11 agricultural fields in the lee of large disused
      industrial plants in the Leipzig-Halle region at varying distances from emitters.
      The investigations clearly indicate the deposition of anthropogenic pollutant
      inputs, not only in the past, but also today. The pollution potential was
      assessed on the basis of current guide values and limits, as well as in relation
      to values found in agricultural soils elsewhere in Germany, in Europe and in the
      USA. The reference values were mainly exceeded for DDX and gamma-HCH (lindane).
      The PCB pattern was determined and the degradation ratios between the parent
      substances and their metabolites (DDX and HCH isomers) were calculated in order
      to distinguish between the previous and current pollutant input of pesticides by
      means of principal component analysis.

PMID- 11589400
TI  - Limitations of controlled experimental systems as models for natural systems: a
      conceptual assessment of experimental practices in biogeochemistry and soil
      science.
AB  - Experimental systems in which phenomena are studied under controlled conditions
      allow scientists to infer causal relationships from observable effects. When
      investigating ecosystems, however, scientists face complex systems. The
      conventional approach is to divide the system into conceptual units and to
      prepare experimental systems accordingly. Experimental systems are used as models
      for ecosystems: initially, scientists assume an analogy between the experimental
      system and ecosystem, then encode the experimental system into a formal system by
      measuring variables, and decode statements from the formal system to the
      ecosystem. We distinguish three types of experimental systems, i.e. laboratory,
      container and field set-ups, further divided into seven subtypes. Starting from
      the premises of experimental systems, we comment on the possibilities and
      limitations of experimentally derived causal relationships and on their
      significance for ecosystem understanding and prediction, illustrated by examples
      from soil science and the environmental sciences. Experimental set-ups have a
      characteristic duration, degree of structural integrity, internal variability and
      boundaries, which relate to conceptual closure and experimental control: control
      tends to be maximum on short time scales, in homogeneous set-ups with analytical
      boundaries, and in systems with few parameters to be observed. Complexity is
      increased at the expense of control. The higher the degree of manipulation,
      however, the better is reproducibility, but the larger is the deviation from
      unique ecosystems with their infinite number of factors. The material realization
      of closed systems is preceded by a conceptual closure of the system. Closure is
      relative to the domain of phenomena of interest, the theory and the list of
      variables selected by the scientist. Successful decoding from experimental
      systems to ecosystems largely depends on the validity of the chosen analogy.
      Laboratory systems are idealized systems which contain a limited number of a
      priori defined variables, and which are shielded from environmental influences.
      In contrast, ecosystems are materially and conceptually open, non-stationary,
      historical systems, in which system-level properties can emerge, and in which
      variables are produced internally. We conclude that when conducting experiments,
      causal factors can be identified, but that causal knowledge derived from
      insufficiently closed systems is invalid. In ecosystems, innumerous factors
      interact, which may enhance, reduce or neutralize the effect of an experimentally
      determined factor. Thus, experimental model systems need to be evaluated for
      concrete, well-defined ecosystems with a concrete history. Increasingly detailed
      studies of isolated phenomena in the laboratory will probably not contribute much
      to ecosystem-level understanding. When conducting experiments, scientists should
      aim at the maximum degree of complexity they can actually handle and they should
      justify the chosen analogy.

PMID- 11589401
TI  - A study for the biological CO2 fixation and utilization system.
AB  - Increased CO2 in the atmosphere is such a serious problem for mankind that many
      research and development approaches are implemented to reduce CO2 emissions. One
      is a biological CO2 fixation using the photosynthetic function of microalgae like
      Chlorella and Synechocystis sp. The target of the project is to achieve a CO2
      fixation rate of 50 g CO2/m2 d, which is 10 times as large as that of the
      temperate forest. The purpose of this study is to clarify the possibilities of
      the biological CO2 fixation system in view of the CO2 balance, energy balance,
      and payback period. The amount of CO2 fixation of the system should be larger
      than the emission of CO2 by operating. Furthermore, the energy consumption of the
      system should also be less than the biochemical energy (enthalpy) of glucose,
      which is made by photosynthesis. After CO2 fixation was completed by the
      microalgae, the biomass must be utilized practically for many markets and the
      initial investment in the system construction could be regained.

PMID- 11589402
TI  - Daily intake of Se by adult population of Mumbai, India.
AB  - The atmospheric Se levels in Mumbai varied between 0.02 and 1.92 ng m(-3) with a
      mean concentration of 0.21 ng m(-3). The daily intake of Se by the adult
      population of Mumbai is 61.9 microg day(-1). Differential pulse cathodic
      stripping voltammetry (DP-CSV) has been used for the determination of Se in air
      particulate and food samples. The detection limit of Se using DPCSV was found to
      be 0.05 ng ml(-1). The reliability of estimation was further assessed through the
      analysis of standard reference materials (SRMs), tuna fish, animal blood, milk
      powder and fish tissue obtained from IAEA. The frequency distribution of dietary
      intake levels of selenium for Mumbai adults showed that approximately 61% of the
      studied population have a dietary intake of 30-90 microg day(-1). Ingestion was
      found to be the main route of Se exposure for Mumbai adults. The turn over time
      of Se through blood is 17 days.

PMID- 11589403
TI  - A Pb isotope and trace element study of rainwater from the Massif Central
      (France).
AB  - Lead isotope ratios and Zn, Pb, Cu, Cd, Sb and Rb contents were measured in
      samples of rainwater collected over a period of 15 months from the Massif Central
      (France). Each sample, collected automatically at monthly intervals, represents a
      series of rainfall events. Rainwater chemistry was interpreted in terms of the
      chemical contributions from wet deposition and from different source regions for
      dust in the centre of France. Trace element concentrations in rainwater samples
      showed a wide range, particularly for Pb (1.30-465 microg/l), with variations
      decreasing for Cd (0.07-1.70 microg/l), Zn (1.00-54.00 microg/l), Cu (0.20-25.00
      microg/l), Sb (approximately 0-0.33 microg/l) and Ni (approximately 0-15.00
      microg/l). Trace element contents do not correlate with rainfall amount and no
      inter-element correlations are evident in the data. Lead is the most common trace
      metal found in the rainwater (mean value = 996 microg/m2/y) while Sb is the least
      common element measured (mean value = 1.12 microg/m2/y). The composition of
      rainwater collected from the Massif Central shows a range in Pb isotope ratios
      from 17.935 to 19.22 (206Pb/204Pb), 15.578 to 15.73 (207Pb/204Pb) and 37.559 to
      38.606 (208Pb/204Pb). A five-component mixing model involving contributions from
      the natural background, gasoline inputs from industrial and agricultural activity
      and a source resulting from mining waste may be used to explain both the Pb
      isotope signature and the fluctuations in trace metal contents of Massif Central
      rainwater.

PMID- 11589404
TI  - The costing of carbon credits from ocean nourishment plants.
AB  - Ocean nourishment is a process for stimulating the sequestration of atmospheric
      carbon dioxide in the deep ocean by providing the nutrients needed to enhance the
      production of phytoplankton. The carbon dioxide sink thus created, can be used to
      generate tradeable carbon credits. The costs of sequestering carbon by the
      process of ocean nourishment have been estimated using as a basis, the previous
      experience in nitrogen fixing of Toyo Engineering Corporation. While there are
      uncertainties about the biological uptake efficiency, these introduce only a
      moderate uncertainty in our overall estimates of costs. The major determinants of
      the costs are the interest that must be paid on capital and the cost of the
      feedstock, natural gas. We have used for discussion purposes, an interest rate of
      4-8% per annum and natural gas costs of US$0.5-$2 per GJ. The costs of carbon
      credits lie in the range US$6.70-$12.40 per tonne of carbon dioxide emissions
      sequestered. It should be noted that we have adopted the measure of carbon
      avoided by non-emission, because of the complex partitioning of anthropogenic
      carbon between the atmosphere, land and ocean.

PMID- 11589405
TI  - A system for protecting the environment from ionising radiation: selecting
      reference fauna and flora, and the possible dose models and environmental
      geometries that could be applied to them.
AB  - In order to demonstrate, explicitly, that the environment can be protected with
      respect to controlled sources of ionising radiation, it is essential to have a
      systematic framework within which dosimetry models for fauna and flora can be
      used. And because of the practical limitations on what could reasonably be
      modelled and the amount of information that could reasonably be obtained, it is
      also necessary to limit the application of such models to a 'set' of fauna and
      flora within a reference' context. This paper, therefore, outlines the factors
      that will need to be considered to select such 'reference' fauna and flora, and
      describes some of the factors and constraints necessary to develop the associated
      dosimetry models. It also describes some of the most basic environmental
      geometrics within which the dose models could be set in order to make comparisons
      amongst different radiation sources.

PMID- 11589406
TI  - Comparison of diffusive gradients in thin films and equilibrium dialysis for the
      determination of Al, Fe(III) and Zn complexed with dissolved organic matter.
AB  - The distinction between 'free' metals and organically complexed metals in aqueous
      solutions is important for research involving the mobility or bioavailability of
      metals in the environment. In this study, the applicability of equilibrium
      dialysis (molecular weight cut-off = 1000 Da) and diffusive gradients in thin
      films (DGT) to determine 'free' Al, Fe(III) and Zn in four forest soil solutions
      was compared. The 'free' metals as measured by both methods, consist of hydrated
      metal cations and soluble inorganic metal complexes. In addition, dialysis
      measures any organic complexes < 1000 Da and DGT measures a portion of smaller
      labile organic complexes. The four soil solutions were prepared by water
      extraction of an organic soil horizon (H) from a Fimic Anthrosol, and contained
      either 20 or 75 mg C/l dissolved organic matter at pH 4.0 and pH 7.0. To test the
      performance of both methods and optimize experimental volume and time,
      experiments using metal nitrate solutions were carried out. In the solutions at
      pH 4.0, no significant differences in average 'free' metal contents were found
      for Al, Fe(III) or Zn. This makes DGT a viable alternative for equilibrium
      dialysis for the study of the complexation of all three metals in acidic soils.
      At pH 7.0, again no significant difference between both methods were found for Al
      and Fe(III), but the DGT results for Zn were significantly higher. This was
      likely caused by labile organic complexes that were only detected by DGT.

PMID- 11589407
TI  - The status and dynamics of some trace elements in a savanna soil under long-term
      cultivation.
AB  - A recent study in the savanna suggested that the surface soils might be
      contaminated with Ti, V, U and Th because of increasing phosphate fertilizer
      applications. In this study, we determined the dynamics of Ga, V, U, Nb, Y, La,
      Ce and Nd in a savanna soil that has received NPK fertilizers, farmyard manure
      (FYM) and FYM + NPK for 50 years using an adjacent uncultivated or native site as
      a reference. The concentrations of the elements in the soils were determined by X
      ray fluorescence. Mass balance calculations indicated that Nb, U, Y, La, Ce and
      Nd increased by between 8 and 61% in the cultivated soil compared with the
      uncultivated natural site. Long-term application of FYM increased the masses of
      Nb (16%), Th (40%), La (26%), Ce (44%) and Nd (54%). There were no discernible
      changes in the masses of the trace elements that could be unambiguously
      associated with phosphate fertilizer applications. It was, thus, concluded that
      physical accumulation as leaching losses and crop removal depleted soluble ions,
      stabilization by organo-mineral complexes and aeolian deposition are the probable
      soil enrichment mechanisms of these trace elements during cultivation.

PMID- 11589408
TI  - Phenolic antioxidants in wood smoke.
AB  - Ten prominent dimethoxyphenols were determined in birchwood smoke from choked and
      open laboratory burning and in chimney smoke from a tiled stove. The structures
      of the methoxyphenols are similar to those of the well-known tocopherol and
      ubiquinol antioxidants. The 2,6-dimethoxyphenols characterising hardwood smoke
      are stronger antioxidants than the corresponding 2-methoxyphenols present mainly
      in softwood smoke. The antioxidant activity is highest for the 2,6
      dimethoxyphenols with 4-alkenyl and 4-alkyl groups, which constitute 60-70% of
      the total amount of dimethoxyphenols. Phenolic antioxidants are scavengers of
      oxygen radicals and should be considered when health hazards of small-scale
      incomplete biomass burning are estimated.

PMID- 11589409
TI  - Chemical reactions occurring during direct solar reduction of CO2.
AB  - At high temperatures carbon dioxide may absorb solar radiation and react to form
      carbon monoxide and molecular oxygen. The CO, so produced, may be converted by
      well-established means to a combustible fuel, such as methanol. We intend to make
      a future demonstration of the solar reduction of CO2 based on these processes.
      This paper, however, addresses only the problem of preserving, or even enhancing,
      the initial photolytic CO by quenching the hot gas with colder H2O or CO2. We
      present model calculations with a reaction mechanism used extensively in other
      calculations. If a CO2 gas stream is heated and photolyzed by intense solar
      radiation and then allowed to cool slowly, it will react back to the initial CO2
      by a series of elementary chemical reactions. The back reaction to CO2 can be
      terminated with the rapid addition of CO2, water, or a mixture. Calculations show
      that a three-fold quench with pure CO2 will stop the reactions and preserve over
      90% of the initial photolytic CO. We find that water has one of two effects. It
      can either increase the CO level, or it can catalyze the recombination of O and
      CO to CO2. The gas temperature is the determining factor. If the quench gas is
      not sufficient to keep the temperature below approximately 1100 K, a chain
      branching reaction dominates and the reaction to CO2 occurs. If the temperature
      stays below that level a chain terminating reaction dominates and the CO is
      increased. The former case occurs below approximately a fourfold quench with a
      water/CO2 mixture. The later case occurs when the quench is greater than
      fourfold. We conclude that CO2, H2O, or a mixture may quench the hot gas stream
      photolyzed by solar radiation and preserve the photolytic CO.

PMID- 11589410
TI  - Are we reaching the target audience? Evaluation of a fish fact sheet.
AB  - According to the US Environmental Protection Agency, over 16% of freshwater lakes
      and 7% of the rivers are under some sort of fish consumption advisory because of
      the presence of toxic chemicals. There is considerable interest in the issuing of
      information, advisories, and fact sheets concerning the consumption of wild
      caught fish from contaminated waters, and in the actual consumption patterns of
      subsistence and recreational anglers. Despite the large number of consumption
      advisories issued by state agencies, there is little information on how these
      advisories, or other forms of risk communication, are perceived by target
      audiences, notably fishermen and women of child-bearing age. The states of South
      Carolina and Georgia issue consumption advisories for fish from the Savannah
      River, among other sites. To gain a greater insight into the perception of
      anglers about a supplemental fish fact sheet jointly developed by South Carolina,
      Georgia, federal agencies, and the Consortium for Risk Evaluation with
      Stakeholder Participation, we interviewed fisherman along the Savannah River. The
      objectives were to determine: (1) whether they had previously read the Fish Fact
      Sheet or had heard about the consumption advisories; (2) what major message they
      obtained from the sheet; (3) who they felt the fact sheet was aimed at, and who
      should get the Fish Fact Sheet; (4) who should be concerned about health risks
      from consuming the fish; and (5) the best method of disseminating such
      information. We interviewed 92 fishermen (37% black, 62% white) during the
      fishing season of 1999. Half had heard some information about consumption
      advisories, mainly from the media (64%). The study concluded that there were no
      ethnic differences in whether they had heard about the advisories, understood the
      major message of the fact sheet, felt they could reduce their risk from consuming
      the fish, or felt that it made a difference which agency issued the fact sheet.
      There were significant ethnic differences in the ways people thought the risk
      from eating fish could be reduced, sources of information about the risks from
      consuming fish, and what other information they would like about the risks
      associated with contaminated fish.

PMID- 11589411
TI  - Catalyzed UV oxidation of organic pollutants in biologically treated wastewater
      effluents.
AB  - A batch reactor was used to evaluate the efficiency of advanced oxidation process
      of the organic pollutants in biologically treated wastewater effluents with
      UV/H2O2. A 450-W high-pressure mercury vapor lamp was used as the light source.
      During the degradation process, the concentration of the dissolved organic
      compounds could be increased by more than twofold due to the decomposition of
      microorganisms. This increase of the dissolved organic compounds was eliminated
      if the water was filtered before the photodegradation experiments. It is observed
      that the UV alone could play a role for the oxidation of the organic pollutants;
      however, the addition of a small amount of hydrogen peroxide promotes the
      degradation efficiency of organic compounds in wastewater. The best oxidation
      efficiency was obtained when the water samples were under acidic conditions (pH
      5), and the rate of degradation was not enhanced with the increasing H2O2
      dosages. The optimum H2O2 dose was between 0.01% and 0.1% for the oxidation
      processes in this study. The presence of the carbonate/bicarbonate ions in water
      inhibits the degradation of the organic compounds.

PMID- 11589412
TI  - Sources and behaviour of bismuth active substances (BiAS) in a municipal sewage
      treatment plant.
AB  - Non-ionic surfactants are widely used for household and industrial purposes. For
      different reasons the metabolites, e.g. 4-nonylphenol, nonylphenol
      monoethoxylate, nonylphenol diethoxylate and 4-tert-octylphenol, are especially
      considered to be endocrine disruptive and thus potentially harmful for the
      environment. In this study, field samples of raw wastewater from different point
      sources, including industrial effluents, household effluents, the influent and
      secondary effluent of a wastewater treatment plant that treats this wastewater
      were monitored simultaneously. Composite samples were taken five times over
      periods of 1 week at nine sample sites. The results showed that the
      concentrations and fluxes were varying. In addition industrial, influent and
      effluent samples were investigated for nonylphenol (NP). The highest
      concentrations of bismuth active substances (BiAS) were obtained by wastewater
      samples from a chemical and a cloth washing company ranging from 10,200 to 65,600
      microg/l and 14,600 to 33,900 microg/l BiAS, respectively. Although the
      concentration of BiAS in the wastewater of the paper production was only between
      460 and 1200 microg/l BiAS, the NP/BiAS ratio of 0.51% was considerably higher
      than in other industrial effluents. The BiAS concentration in wastewater samples
      from households ranged from 2200 to 7900 microg/l BiAS, but the NP concentration
      was quite low, 0.01% of BiAS. This could be due to the effort within the EU to
      phase out nonylphenol polyethoxylates in household detergents. Influent
      concentrations between 700 and 2200 microg/l BiAS with removal rates in the WWTP
      ranging from 70.7 to 99.4% with an average of 92.2% could be measured.

PMID- 11589414
TI  - Impact of altering DSM-IV criteria for anorexia and bulimia nervosa on the base
      rates of eating disorder diagnoses.
AB  - The diagnostic criteria used to define eating disorders have been the focus of
      debate for many years. The primary aim of this study was to evaluate the impact
      of altering DSM-IV diagnostic criteria upon the base rates of anorexia nervosa
      (AN), bulimia nervosa (BN) and eating disorder not otherwise specified (EDNOS).
      Five controversial criteria were systematically modified and the impact of these
      changes on base rates of full-syndrome and partial-syndrome eating disorders was
      assessed in 193 patients referred to two specialty eating disorder clinics.
      Modification of a single criterion resulted in relatively small changes in base
      rates of AN and BN, whereas modification of the two severity criteria led to more
      substantial changes. These findings have significant implications for future
      modifications of the DSM classification.

PMID- 11589413
TI  - What treatments patients seek after inpatient care: a follow-up of 24 patients
      with anorexia nervosa.
AB  - BACKGROUND: To determine the kind of treatment patients with anorexia nervosa
      (AN) seek for their eating disorder following hospitalization. METHOD: Twenty
      four women previously treated in the Toronto General Hospital were interviewed to
      determine the nature and amount of treatment received following discharge.
      RESULTS: Mean age: 31 years (SD=9.18). Mean body mass index (BMI) at assessment:
      19.97 (SD=4.00). All had seen at least one or more professionals, mainly family
      doctors and psychiatrists, within the first 6 months. Mean hours of treatment:
      85. Eighty-eight per cent had taken psychotropic medication (most commonly
      antidepressants). Symptomatic and asymptomatic patients did not differ in amount
      of treatment received. CONCLUSIONS: Regardless of their symptom state, AN
      patients continue to use the health system heavily following weight restoration.
      Their aftercare is thus essential for ongoing maintenance treatment and to
      prevent relapse, and training primary-care physicians to provide it may be one
      way to contain health care costs.

PMID- 11589415
TI  - Cigarette smoking and its relationship to other substance use among eating
      disordered inpatients.
AB  - OBJECTIVE: The present study examines prevalence rates of tobacco, caffeine,
      alcohol and other substance use and abuse among eating disordered inpatients and
      compares smokers (regular vs occasional vs non-smokers) and eating disorder (ED)
      subtypes [anorexia nervosa (AN) vs bulimia nervosa (BN); restrictors vs purgers]
      on substance use behaviors, family history, depressive symptoms and impulsivity.
      METHOD: Participants were 100 ED inpatients who completed assessment upon
      treatment entry. RESULTS: A high incidence of regular cigarette smoking (29%) and
      occasional smoking (13%) was detected and associations were found with caffeine
      abuse, alcohol and marijuana use, family history and depression. BNs were more
      likely to smoke occasionally and use alcohol than ANs, while Purgers demonstrated
      higher caffeine and alcohol use than Restrictors. DISCUSSION: Comprehensive
      assessment and intervention for smoking, caffeine and other substance use among
      ED patients is clearly indicated.

PMID- 11589416
TI  - Neurocognitive evidence favors "top down" over "bottom up" mechanisms in the
      pathogenesis of body size distortions in anorexia nervosa.
AB  - Perceptually-based disturbances in body image, or body size distortions, have
      been posited to occur in anorexia nervosa (AN). Perception does not result from a
      simple flow of sensory information from periphery to cortex ("bottom-up"
      processing), but involves the selection of inputs most likely to be relevant in
      light of an individual's experience and expectations ("top-down" processing).
      Most investigations of body size distortion in AN have used procedures likely to
      engage top-down processing, raising the possibility that attitudinal disturbances
      may play a role. To our knowledge, there have been no studies that assess the
      presence, in AN, of neurocognitive deficits associated with neurologically based
      disturbances in body schema. Such deficits, if found, could provide evidence of
      body image distortion unlikely to result from top-down processing. We tested 20
      inpatients with AN on measures of proprioception, finger identification,
      right/left orientation, general cognition and eating disorders symptomatology,
      both before and after treatment. Matched normal controls were tested on the same
      measures over the same time intervals. Significant differences between the two
      groups occurred only prior to treatment, and only on those measures which
      involved executive, in addition to more body-schema-specific functions. This
      suggests that patients with AN do not have enduring deficits in the domain of
      body-schema, but may have subtle cognitive dysfunction, in the acute state, which
      is not specific to, but can interact with processing of body-schema-related
      information. This, in turn, suggests that their body image distortion may not be
      secondary to bottom-up perceptual disturbances.

PMID- 11589417
TI  - Relationships between objective physical characteristics and the use of weight
      control methods in adolescence: a mediating role for eating attitudes?
AB  - This study of non-clinical adolescent males and females examined associations of
      objectively measured physical characteristics with greater use of methods of
      weight control and considered whether the relationships between these variables
      might be explained by a mediating effect of a subjective characteristic-
      unhealthy eating attitudes. Non-clinical male and female adolescents completed
      measures of weight control and eating attitudes, and their physical
      characteristics were measured using a range of standardized anthropometry
      techniques. Regression analyses were used to test the role of eating attitudes as
      mediators in the relationship between physical characteristics and the use of
      weight control methods. The data were compatible with a partial mediator model,
      where physical characteristics influence eating attitudes, and those where
      attitudes drive the use of methods to control weight. However, not all of the
      relationship was explained by this mediator. In addition, there were different
      patterns of association for men and women, consistent with different patterns of
      bodily focus between the genders. These findings stress the importance of
      understanding objective physical characteristics as well as subjective eating
      attitudes to find out why people use different levels of weight control
      behaviours. Limitations, further research and potential implications for clinical
      and preventative programmes are discussed.

PMID- 11589418
TI  - Psychopathological and clinical features of outpatients with an eating disorder
      not otherwise specified.
AB  - In order to investigate similarities and differences between Eating Disorder Not
      Otherwise Specified (EDNOS) and Anorexia Nervosa (AN) and Bulimia Nervosa (BN),
      we studied a consecutive series of 189 female outpatients attending two Eating
      Disorder Units. The data were collected by means of interviews (Eating Disorder
      Examination, EDE 12.0D), the Structured Diagnostic Interview for DSM III-R,
      (SCID), and self-reported questionnaires (Beck Depression Inventory, BDI, and
      State and Trait Anxiety Inventory, STAI 1-2). The diagnosis of EDNOS was as
      frequent as that of AN and BN (43.8% versus 43.2%). There were no significant
      differences between EDNOS and AN/BN patients in terms of their general and
      specific psychopathological features, but significant differences were observed
      between bulimic-like and anorectic-like EDNOS patients, as well as between those
      with AN and BN. In conclusion, in our clinical setting, the patients with EDNOS
      and those with typical eating disorders have similar psychopathological features,
      thus suggesting that EDNOS patients should be further divided into two groups,
      anorectic-like (similar to AN) and bulimic-like (similar to BN) patients.

PMID- 11589419
TI  - Attachment processes in eating disorders.
AB  - Anxious and insecure attachment, fear of abandonment and difficulties with
      autonomy differentiate young women with eating disorders from their normal peers.
      This paper uses the Adult Attachment Interview (AAI) as the correlation between
      eating disorders and state of mind regarding attachment (7 females and 6 males)
      with anorexia nervosa and EDNOS. There was a higher frequency of dismissing or
      entangled states of mind. The sample is far too small to allow statistical
      inferences to be drawn about differences between men and women in the style of
      state of mind regarding attachment. An inference is none the less made with
      regard to the role of psychotherapy in these results.

PMID- 11589420
TI  - About orlistat.

PMID- 11589421
TI  - Potential environmental and host participants in the early white matter lesion of
      adreno-leukodystrophy: morphologic evidence for CD8 cytotoxic T cells, cytolysis
      of oligodendrocytes, and CD1-mediated lipid antigen presentation.
AB  - The 2 most common forms of X-linked adreno-leukodystrophy (ALD) are the juvenile
      or childhood cerebral form with inflammatory demyelination and the adult
      adrenomyeloneuropathy (AMN) involving spinal cord tracts without significant
      inflammation. Modifier genes or environmental factors may contribute to the
      phenotypic variability. We performed immunohistochemical, an in situ polymerase
      chain reaction, and TUNEL analyses to identify several viruses, lymphocyte
      subpopulations, apoptotic cells, and effector molecules, focusing on
      morphologically normal white matter, dysmyelinative and acute demyelinative
      lesions. No distinguishing viral antigens were detected. Most lymphocytes were
      CD8 cytotoxic T cells (CTLs) with the alpha/beta TCR, and they infiltrated
      morphologically unaffected white matter. Only a few oligodendrocytes were
      immunoreactive for caspase-3. MHC class II- and TGF-beta-positive microglia were
      present. CD44, which can mediate MHC-unrestricted target cell death, was seen on
      many lymphocytes and white matter elements. CD1 molecules, which play major roles
      in MHC-unrestricted lipid antigen presentation, were noted. Our data indicate
      that unconventional CD8 CTLs are operative in the early stages of
      dysmyelination/demyelination and that cytolysis of oligodendrocytes, rather than
      apoptosis, appears to be the major mode of oligodendrocytic death. The
      presentation of lipid antigens may be a key pathogenetic element in ALD and AMN
      ALD.

PMID- 11589422
TI  - Alzheimer disease therapeutics.
AB  - Alzheimer disease (AD) is characterized pathologically by cholinergic deficits,
      amyloid plaques, neurofibrillary tangles, gliosis, and neuronal and synaptic
      loss. The primary therapeutic approach that has arisen from the pathological
      analysis of AD brain has been cholinergic augmentation by cholinesterase
      inhibitors, which modestly improve cognitive function. Research on the underlying
      pathophysiological dysfunction have focussed on AD-specific processes such as
      amyloid precursor protein, tau, and cerebral apolipoprotein E metabolism, and
      more general neurodegenerative processes such as inflammation, oxidation,
      excitotoxicity, and apoptosis. Rational neuroprotective approaches have led to
      recent trials of estrogen, antioxidant and anti-inflammatory medications in AD,
      and to the development of anti-amyloid strategies for delaying progression or
      preventing development of AD.

PMID- 11589423
TI  - Synaptic pathology in prefrontal cortex is present only with severe dementia in
      Alzheimer disease.
AB  - Synaptic pathology is proposed to be integral to the clinical expression of
      Alzheimer disease (AD). Most studies have assessed only the vesicle protein
      synaptophysin as a measure of synaptic integrity. The interrelationships of
      synaptophysin, other presynaptic proteins, the cholinergic system, and severity
      of dementia in AD remain unclear. We studied the presynaptic proteins
      synaptophysin, syntaxin and SNAP-25, along with choline acetyltransferase (ChAT)
      activity in prefrontal cortex (BA 46) samples from 18 subjects with AD and 16
      controls. Mean values of presynaptic protein immunoreactivities were
      significantly reduced, by 21%-28%, and ChAT activity was reduced by 41% in the AD
      groups. Synaptic protein immunoreactivity and ChAT activity were correlated with
      Mini-Mental State Examination scores obtained 1 yr prior to death. When AD cases
      were subgrouped into mild/moderate and severe illness at time of death, all
      differences in presynaptic proteins and ChAT activity were significant between
      controls and severe cases. However, no significant differences were detected in
      BA 46 between controls and mild/moderate cases. Considerable synaptic reserve or
      plasticity remains in BA 46 until the late stages of AD. Synaptophysin and ChAT
      appear to be more vulnerable in severe AD than are syntaxin or SNAP-25.

PMID- 11589424
TI  - Chloroquine-induced neuronal cell death is p53 and Bcl-2 family-dependent but
      caspase-independent.
AB  - Chloroquine is a lysosomotropic agent that causes marked changes in intracellular
      protein processing and trafficking and extensive autophagic vacuole formation.
      Chloroquine may be cytotoxic and has been used as a model of lysosomal-dependent
      cell death. Recent studies indicate that autophagic cell death may involve Bcl-2
      family members and share some features with caspase-dependent apoptotic death. To
      determine the molecular pathway of chloroquine-induced neuronal cell death, we
      examined the effects of chloroquine on primary telencephalic neuronal cultures
      derived from mice with targeted gene disruptions in p53, and various caspase and
      bcl-2 family members. In wild-type neurons, chloroquine produced concentration-
      and time-dependent accumulation of autophagosomes, caspase-3 activation, and cell
      death. Cell death was inhibited by 3-methyladenine, an inhibitor of autophagic
      vacuole formation, but not by Boc-Asp-FMK (BAF), a broad caspase inhibitor.
      Targeted gene disruptions of p53 and bax inhibited and bcl-x potentiated
      chloroquine-induced neuron death. Caspase-9- and caspase-3-deficient neurons were
      not protected from chloroquine cytotoxicity. These studies indicate that
      chloroquine activates a regulated cell death pathway that partially overlaps with
      the apoptotic cascade.

PMID- 11589425
TI  - Clinical validity of A beta-protein deposition staging in brain aging and
      Alzheimer disease.
AB  - Braak's neurofibrillary tangle (NFT) pathology staging system of Alzheimer
      disease (AD) correlates generally with clinical data. Recently, Braak's group
      proposed an Abeta-protein staging based on the progression of amyloid deposition
      in the medial temporal lobe. To examine its clinical validity and evaluate
      whether it adds predictive power to NFT-based staging, we performed a study
      comparing both neuropathological classifications with clinical dementia rating
      scale (CDR) scores in a large autopsy series. The 2 neuropathological staging
      systems were strongly correlated. Their association with clinical severity was
      highly significant. However, the strength of the relationship was greater for NFT
      based staging. It accounted for 26.5% of the variability in clinical severity,
      Abeta-protein-based staging for 13.0%, and age for 4.4%. Compared to NFT-based
      staging, the Abeta-protein-based system was less able to distinguish mild
      cognitive changes from dementia and showed marked overlap among the various
      stages of cognitive decline. In a multivariate model, NFT and age together
      accounted for 27.2% of the clinical variability and the addition of Abeta-protein
      deposition staging could only explain an extra 2.9%. Our data support the close
      relationship between NFT progression and amyloid formation within the medial
      temporal lobe proposed by Braak's group but demonstrate the limited value of
      Abeta-protein deposition staging in terms of clinicopathological correlations.

PMID- 11589426
TI  - TX14(A), a prosaposin-derived peptide, reverses established nerve disorders in
      streptozotocin-diabetic rats and prevents them in galactose-fed rats.
AB  - Recently, TX14(A), a prosaposin-derived neurotrophic peptide, was shown to
      prevent both large and small fiber deficits in streptozotocin diabetes. Here, the
      efficacy of TX14(A) in reversing established nerve conduction disorders in
      streptozotocin diabetes, a model of insulin deficiency, and preventing them in
      galactose feeding, an insulin-replete model of polyol pathway flux, was
      investigated. Following streptozotocin injection (50 mg/kg ip), TX14(A) treatment
      (1 mg/kg ip thrice weekly) was initiated in half of the animals. After 8 wk,
      treatment was begun in half of the untreated animals and discontinued in half of
      the treated animals, and the experiment continued for 6 wk. TX14(A) reversed
      established motor and sensory nerve conduction deficits in streptozotocin
      diabetic rats and the impact of previous treatment was still evident 3 wk after
      withdrawal. With the onset of 40% galactose feeding, the same dose of TX14(A) was
      given to half of the control and half of the galactose-fed animals for 16 wk.
      TX14(A) was without effect in control animals but it attenuated motor and sensory
      nerve conduction deficits in galactose-fed rats, an effect associated with
      amelioration of axonal dwindling in the sciatic nerve. These observations extend
      the therapeutic utility of TX14(A) and highlight its potential in treating
      established diabetic neuropathy.

PMID- 11589427
TI  - Interleukin-1 beta is required for the early evolution of reactive astrogliosis
      following CNS lesion.
AB  - The CNS response to injury is characterized by the rapid activation of astrocytes
      in a process known as astrogliosis. The function of reactive astrocytes is
      controversial, in that both beneficial and detrimental properties are postulated.
      Identification of the molecules involved in regulating astrogliosis is an
      important step towards understanding astrocyte functions and establishing
      suitable conditions for CNS regeneration. We previously reported that
      inflammatory cytokines are regulators of astrogliosis but the key cytokine
      involved in initiating astrogliosis was unclear. We describe here that the
      elevation of glial fibrillary acid protein (GFAP) transcripts follows the very
      early rise of interleukin (IL)-1beta mRNA in a murine corticectomy model of CNS
      lesion. Furthermore, the injury-induced upregulation of GFAP mRNA and protein did
      not occur in mice genetically deficient for IL-1beta compared to wild-type
      animals. This was correlated with an absence of an increase in GFAP
      immunoreactivity (GFAP-ir) in IL-1beta-null mice at 2 and 3 days of injury.
      However, by 5 to 7 days after the lesion, GFAP-ir was not different between
      cytokine-deficient and wild-type controls. Functionally, mice lacking IL-1beta
      exhibited a significant impairment in reformation of the blood-brain barrier
      (BBB) following corticectomy compared to wild-type controls. These findings
      suggest that the rapid production of IL-1beta following trauma plays a beneficial
      role in initiating astrogliosis in an attempt to restore the integrity of the BBB
      and seal off the wound site.

PMID- 11589428
TI  - Altered immediate early gene expression in injured diabetic nerve: implications
      in regeneration.
AB  - To study the role that immediate early gene responses may play in impaired nerve
      fiber regeneration in diabetes, diabetic male BB/Wor rats were subjected to
      sciatic nerve crush at 6 wk of diabetes. Sciatic nerve mRNA expression of IGF-I,
      IGF-1-receptor, NGF, and p75 (low affinity NGF receptor), as well as protein
      expression of C-FOS, were examined at various time points following crush injury
      and compared with age- and sex-matched nondiabetic BB/Wor rats. Diabetic rats
      showed a delay in the early peak expression of IGF-1, C-FOS, NGF, and p75. The
      earliest immediate gene responses were those of IGF-I and IGF-1-receptor, which
      peaked at 0.5 h post-crush in control rats. In diabetic rats, IGF-1 peaked at 24
      h whereas IGF-1-receptor mRNA revealed no early peak. The early NGF mRNA
      expression showed a maximum response at 6 h and of p75 at 4 days post-crush in
      control rats, whereas in diabetic rats they occurred at 2 days and 6 days,
      respectively. C-FOS protein expression showed a maximum at 6 h in control rats
      and in diabetic animals an attenuated peak was present at 2 days. These data
      provide the first evidence that immediate early gene responses are delayed in
      diabetes following sciatic nerve crush injury. The delayed IGF-1 expression may
      affect C-FOS induction and may be responsible for the delay in the NGF response
      in diabetic rats. The delayed immediate early gene responses precede the
      previously described perturbed macrophage recruitment and delayed Wallerian
      degeneration in this type I model and provide a possible explanation for impaired
      nerve regeneration in diabetes.

PMID- 11589429
TI  - Distinct expression pattern of microtubule-associated protein-2 in human
      oligodendrogliomas and glial precursor cells.
AB  - Microtubule-associated protein 2 (MAP2), a protein linked to the neuronal
      cytoskeleton in the mature central nervous system (CNS), has recently been
      identified in glial precursors indicating a potential role during glial
      development. In the present study, we systematically analyzed the expression of
      MAP2 in a series of 237 human neuroepithelial tumors including paraffin-embedded
      specimens and tumor tissue microarrays from oligodendrogliomas, mixed gliomas,
      astrocytomas, glioblastomas, ependymomas, as well as dysembryoplastic
      neuroepithelial tumors (DNT), and central neurocytomas. In addition, MAP2
      immunoreactive precursor cells were studied in the developing human brain. Three
      monoclonal antibodies generated against MAP2A-B or MAP2A-D isoforms were used.
      Variable immunoreactivity for MAP2 could be observed in all gliomas with the
      exception of ependymomas. Oligodendrogliomas exhibited a consistently strong and
      distinct pattern of expression characterized by perinuclear cytoplasmic staining
      without significant process labeling. Tumor cells with immunoreactive bi- or
      multi-polar processes were mostly encountered in astroglial neoplasms, whereas
      the small cell component in neurocytomas and DNT was not labeled. These features
      render MAP2 immunoreactivity a helpful diagnostic tool for the distinction of
      oligodendrogliomas and other neuroepithelial neoplasms. RT-PCR, Western blot
      analysis, and in situ hybridization confirmed the expression of MAP2A-C
      (including the novel MAP2+ 13 transcript) in both oligodendrogliomas and
      astrocytomas. Double fluorescent laser scanning microscopy showed that GFAP and
      MAP2 labeled different tumor cell populations. In embryonic human brains, MAP2
      immunoreactive glial precursor cells were identified within the subventricular or
      intermediate zones. These precursors exhibit morphology closely resembling the
      immunolabeled neoplastic cells observed in glial tumors. Our findings demonstrate
      MAP2 expression in astrocytic and oligodendroglial neoplasms. The distinct
      pattern of immunoreactivity in oligodendrogliomas may be useful as a diagnostic
      tool. Since MAP2 expression occurs transiently in migrating immature glial cells,
      our findings are in line with an assumed origin of diffuse gliomas from glial
      precursors.

PMID- 11589431
TI  - NHS plans in the United Kingdom.

PMID- 11589430
TI  - Aggressive phenotypic and genotypic features in pediatric and NF2-associated
      meningiomas: a clinicopathologic study of 53 cases.
AB  - Pediatric and NF2-associated meningiomas are uncommon and poorly characterized in
      comparison to sporadic adult cases. In order to elucidate their molecular
      features, we analyzed MIB-1, progesterone receptor (PR), NF2, merlin, DAL-1, DAL
      1 protein, and chromosomal arms 1p and 14q in 53 meningiomas from 40
      pediatric/NF2 patients using immunohistochemistry and dual-color fluorescence in
      situ hybridization (FISH). Fourteen pediatric (42%) patients, including 5
      previously undiagnosed patients, had NF2. The remaining 19 (58%) did not qualify.
      All 7 of the adult patients had NF2. Meningioma grading revealed 21 benign (40%),
      26 atypical (49%), and 6 anaplastic (11%) examples. Other aggressive findings
      included high mitotic index (32%), high MIB-1 LI (37%), aggressive variant
      histology (e.g. papillary, clear cell) (25%), brain invasion (17%), recurrence
      (39%), and patient death (17%). FISH analysis demonstrated deletions of NF2 in
      82%, DAL-1 in 82%, 1p in 60%, and 14q in 66%. NF2-associated meningiomas did not
      differ from sporadic pediatric tumors except for a higher frequency of merlin
      loss in the former (p = 0.020) and a higher frequency of brain invasion in the
      latter (p = 0.007). Thus, although pediatric and NF2-associated meningiomas share
      the common molecular alterations of their adult, sporadic counterparts, a higher
      fraction are genotypically and phenotypically aggressive. Given the high
      frequency of undiagnosed NF2 in the pediatric cases, a careful search for other
      features of this disease is warranted in any child presenting with a meningioma.

PMID- 11589432
TI  - The evidence for rickettsial disease arising in New Zealand--emergence of a new
      area of endemicity?

PMID- 11589433
TI  - The evidence for rickettsial disease arising in New Zealand.
AB  - AIM: To describe the first cases of serologically proven riskettsial disease
      reported in non-travelling New Zealanders. METHODS: We used clinical and
      laboratory based surveillance, review of clinical records and patient interviews.
      Information collected included demographics, presenting signs and symptoms,
      laboratory results, treatment and outcome. A limited seroprevalence study of
      rural-living friends and relatives was performed. We tested for rickettsial
      antibodies in the sera of possums trapped on properties close to the area of
      residence of the first two cases. RESULT: Serological results support the
      diagnosis of a rickettsial disease in nine patients. Clinical findings at
      presentation were nonspecific but included fever, rigors and headache. A rash was
      noted in four (44%). All had abnormal liver enzymes. Eight were hospitalised. No
      patient died but two were admitted to intensive care. CONCLUSIONS: There is
      strong clinical and serological evidence that Rickettsia typhi (the causative
      organism of murine typhus) or a Rickettsia typhi-like organism is present in the
      greater Auckland region. To prove it, the organism will need to be cultured or
      rickettsial DNA detected by molecular methods. Rickettsial infection needs to be
      included in the differential diagnosis of patients presenting with fever,
      headache and myalgia, particularly in those with rural lifestyles at least in the
      greater Auckland area.

PMID- 11589435
TI  - The impact of the National Cervical Screening Programme on the presentation of
      cancer of the cervix in Canterbury.
AB  - AIMS: To assess the impact of the introduction of the National Cervical Screening
      Programme (NCSP) on the presentation of women with cervical cancer to
      Christchurch Women's Hospital (CWH), a tertiary referral center in Canterbury.
      METHOD: A retrospective review of the hospital notes of patients diagnosed with
      invasive cervical cancer from January 1988 to December 1990 and from January 1997
      to December 1999. The patient characteristics, mode of presentation and staging
      during these two three-year study periods were compared. RESULTS: There was a 21%
      decline in the number of cases of invasive cervical cancer treated at CWH from
      the Canterbury region from the first to the second study period. There was also a
      significant clinical down staging at presentation and a significant increase in
      women presenting with asymptomatic smear detected disease (p=0.004). These
      changes were less marked in women older than 50 years. There was no change in the
      relative proportions of different histological types. CONCLUSION: The results
      reflect a positive impact on the presentation of cervical cancer associated with
      the introduction of the NCSP in Canterbury. A significant decrease in mortality
      from cervical cancer in the region can be anticipated. Further emphasis needs to
      be placed on prevention of cervical cancer in women over 50 years of age.

PMID- 11589434
TI  - Treatment  practices for chlamydial infection in New Zealand.
AB  - AIMS: To identify prescribing and treatment practices for chlamydial infection in
      New Zealand. METHODS: Postal survey to doctors and nurses at all sexual health,
      family planning, student and youth health centres, and randomly selected general
      practitioners. RESULTS: There was considerable variation in treatment regimes
      used for chlamydial infection with few respondents treating in accordance with
      international guidelines regarding dose, frequency, and duration of treatment.
      Doxycycline (88.4%) was most commonly used to treat uncomplicated chlamydial
      infection in non-pregnant patients. Most respondents (70.2%) stipulated
      doxycycline for longer durations than the seven day regimen international
      guidelines recommend, with doxycycline 100 mg twice a day for ten days most
      frequently specified. Among the 259 respondents who would treat pregnant women
      with erythromycin, 51 different treatment regimens were specified, and 51.7%
      recorded regimens less than that recommended by international guidelines. When
      treating a patient presumptively, the majority of respondents tested for
      chlamydial infection. In contrast to other respondents, sexual health clinic
      staff rarely provide patients with a prescription for a patient's partner without
      seeing the partner. CONCLUSIONS: Standardised treatment guidelines are required
      for patients diagnosed with chlamydial infection. Guidelines should include
      recommendations for the treatment of partners, and encourage the laboratory
      confirmation of diagnosis.

PMID- 11589436
TI  - Paradoxical vocal fold dysfunction: a frequently mis(sed) diagnosis.

PMID- 11589437
TI  - Resolution of Menetrier's disease after Helicobacter pylori eradication therapy.

PMID- 11589438
TI  - Isolation in time: a cause of suffering in the elderly. Lessons from Krapp's Last
      Tape.

PMID- 11589439
TI  - A time for evidence-based health planning. Government failure?

PMID- 11589440
TI  - Government failure?

PMID- 11589441
TI  - Government failure?

PMID- 11589442
TI  - Accountability.

PMID- 11589443
TI  - Primary prevention of cardiovascular events.

PMID- 11589444
TI  - Adverse events feasibility study: methodology.

PMID- 11589445
TI  - NHI address coding--is it a threat to the potential of population health
      surveillance?

PMID- 11589446
TI  - It won't happen again--until next time!

PMID- 11589447
TI  - Editorials.

PMID- 11589448
TI  - Immunisation coverage in Tairawhiti.

PMID- 11589449
TI  - General practice and obstetrics. Letter to the Minister of Health.

PMID- 11589450
TI  - Medical research strategy at 2001.

PMID- 11589451
TI  - Lagochilascariasis: an exotic disease from Central and South America.

PMID- 11589452
TI  - Development of sensitive high-performance liquid chromatography with fluorescence
      detection using 4-(4,5-diphenyl-1H-imidazol-2-yl)-benzoyl chloride as a labeling
      reagent for determination of bisphenol A in plasma samples.
AB  - A sensitive HPLC method for determination of bisphenol A (BPA) in plasma samples
      using 4-(4,5-diphenyl-1H-imidazol2-yl)benzoyl chloride (DIB-Cl) as a fluorescence
      labeling reagent was developed. The fluorescence labeling reaction was completed
      within 10 min at room temperature. DIB-Cl reacts with the phenolic hydroxyl group
      of BPA in the presence of triethylamine (TEA). The DIB-Cl derivative of BPA (DIB
      BPA) was separated within 30 min with an ODS column using acetonitrile-water
      (90:10, v/v) as the isocratic eluent. Calibration graphs were linear over the
      range of 1.0-100 ng/ml (r=0.999). The detection limit of DIB-BPA was 0.05 ng/ml
      (2.5 pg) at a signal-to-noise ratio of 3. The relative standard deviations (RSDs)
      of the method for between-run were 1.0-5.0%. The analytical recoveries of known
      amounts (1.0 and 100 ng/ml) of BPA-spiked rabbit plasma were around 95%.

PMID- 11589453
TI  - Sensitive determination of four general anaesthetics in human whole blood by
      capillary gas chromatography with cryogenic oven trapping.
AB  - Four general anaesthetics, sevoflurane, isoflurane, enflurane and halothane, in
      human whole blood, have been found measurable with very high sensitivity by
      capillary gas chromatography-flame ionization detection (GC-FID) with cryogenic
      oven trapping upon injection of headspace (HS) vapor sample. To a 7-ml vial,
      containing 0.48 ml of distilled water and 20 microl of internal standard solution
      (5 microg), a 0.5-ml of whole blood sample spiked with or without anaesthetics,
      was added, and the mixture was heated at 55 degrees C for 15 min. A measure of 10
      ml HS vapor was injected into the GC in the splitless mode at -40 degrees C oven
      temperature, which was programmed up to 250 degrees C. All four peaks were
      clearly separated; no impurity peaks were found among their peaks. Their
      extraction efficiencies were about 10%. The calibration curves showed good
      linearity in the range of 0.5-20 microg/ml; their detection limits were 10-100
      ng/ml, which are almost comparable to those by previous reports. The coefficients
      of intra-day and day-to-day variations were 6.5-9.8 and 7.3-17.2%, respectively.
      Isoflurane or enflurane was also measured from whole blood samples in which three
      volunteers inhaled each compound.

PMID- 11589454
TI  - A sensitive and specific assay for glutathione with potential application to
      glutathione disulphide, using high-performance liquid chromatography-tandem mass
      spectrometry.
AB  - We have utilised the combination of sensitivity and specificity afforded by
      coupling high-performance liquid chromatography (HPLC) to a tandem mass
      spectrometer (MS-MS) to produce an assay which is suitable for assaying
      glutathione (GSH) concentrations in liver tissue. The sensitivity suggests it may
      also be suitable for extrahepatic tissues. The method has been validated for GSH
      using mouse liver samples and also allows the assay of GSSG. The stability of GSH
      under conditions relevant to the assay has been determined. A 20-microl amount of
      a diluted methanol extract of tissue is injected with detection limits of 0.2
      pmol for GSH and 2 pmol for GSSG. The HPLC uses an Altima C18 (150 x 4.6 mm, 5
      microm) column at 35 degrees C. Chromatography utilises a linear gradient from 0
      to 10% methanol in 0.1% formic acid over 5 min, with a final isocratic stage
      holding at 10% methanol for 5 min. Total flow rate is 0.8 ml/min. The transition
      from the M+H ion (308.1 m/z for GSH, and 613.3 m/z for GSSG) to the 162.0 m/z
      (GSH) and 355.3 m/z (GSSG) fragments are monitored.

PMID- 11589455
TI  - High-performance liquid chromatographic method to analyze picomole levels of
      glutathione, cysteine and cysteinylglycine and its application to pre-cancerous
      rat livers.
AB  - A HPLC-based method for quantifying glutathione, cysteine and cysteine-containing
      peptide is described. N-(2,4-Dinitrophenylaminoethyl)maleimide was synthesized
      from ethylenediamine, 2,4-dinitrochlorobenzene and maleic anhydride. The
      maleimide was reacted at 40 degrees C and pH 5.8 for 10 min with thiol compounds
      such as glutathione or cysteine. An aliquot of the reaction mixtures was applied
      to a reversed-phase column (4.6 x 150 mm) of HPLC. When glutathione and cysteine
      were simultaneously assayed, the column was eluted with a gradient of
      acetonitrile in potassium phosphate (pH 7.0). The derivatives were monitored at
      350 nm. Good liner relationships existed between peak area and concentration of
      glutathione or cysteine from 10 pmol to 2 nmol. The recovery tests from rat liver
      homogenate were 99.7+/-2.2% for glutathione and 104.9+/-3.8% for cysteine. By
      this method gamma-glutamylcysteine, cysteinylglycine, and homocysteine could be
      also quantified. The determination limits of glutathione, cysteine and other
      thiol compounds were 5 pmol. The method is simple: a sample solution is mixed
      with the labelling reagent and an aliquot of the reaction mixture is applied to a
      standard HPLC. The hepatic levels of cysteine and glutathione in pre-cancerous
      rats were determined by this method. The cysteine level in pre-cancerous livers
      was extremely elevated in comparison to that of the control groups, while no
      difference was observed in the glutathione contents between the pre-cancerous and
      control groups.

PMID- 11589456
TI  - Fluorogenic assay for beta-glucuronidase using microchip-based capillary
      electrophoresis.
AB  - Microchip capillary electrophoresis (CE) was used with a model enzyme assay to
      demonstrate its potential application to combinatorial drug screening. Hydrolysis
      with beta-glucuronidase of the conjugated glucuronide, fluorescein mono-beta-D
      glucuronide (FMG), liberated the fluorescent product, fluorescein. FMG and
      fluorescein were detected by fluorescence, with excitation and emission at 480
      and 520 nm, respectively. Microchip CE was used to separate FMG and fluorescein.
      Fluorescein production was monitored to assess beta-glucuronidase activity.
      Michaelis-Menten enzyme kinetics analysis yielded the Km value. The results were
      compared with those from experiments done by conventional CE. The Km value for
      beta-glucuronidase with FMG is being reported for the first time as 18 microM.
      The inhibition of beta-glucuronidase by the competitive inhibitor D-saccharic
      acid-1,4-lactone (SL) was also determined using microchip CE. Reactions were done
      with various concentrations of inhibitor and constant beta-glucuronidase and FMG
      concentrations. A dose-response plot was acquired and the IC50 value for SL was
      determined to be 3 microM.

PMID- 11589457
TI  - Trace determination of 1-octacosanol in rat plasma by solid-phase extraction with
      Tenax GC and capillary gas chromatography.
AB  - 1-Octacosanol is the major component of policosanol, a new natural lowering
      cholesterol agent. A sensitive solid-phase extraction with a Tenax GC capillary
      gas chromatography method for determining the proportion of this fatty alcohol in
      plasma after its denaturation with trichloroacetic acid was developed. The
      trimethylsilyl ether derivative of the target analyte obtained from the organic
      extract showed excellent chromatographic properties and was detectable in the low
      nanogram range (1 ng/ml). Adequate separation from plasma's extract was achieved
      with a fused-silica capillary column (30m x 0.25 mm I.D.) with SPB-5 (0.5 microm
      film thickness) and operated with temperature programming from 100 to 200 degrees
      C at 40 degrees C/min and from 200 degrees C increased at 10 degrees C/min to 320
      degrees C, then held for 30 min, the carrier gas flow-rate (argon) was 1 ml/min.
      Quantification was performed by the internal standard method using 1-hexacosanol.
      The reliable relative retention parameters and the mass response factors values,
      and their confidence levels, ensure a proper GC sensitivity, necessary for the
      determination of the alcohol being analyzed. The method was evaluated to a
      concentration range from 6 to 47.6 ng/ml of plasma obtaining recoveries from 95
      to 98%. The correlation between the theoretical concentration values and the
      corresponding experimental values was appropriate (gamma=0.9718 x -0.0915;
      r2=0.9998). The method showed a good within-day (RSD=4.3%) and between-day
      (RSD=6.0%) precision according to the acceptance criteria (<10%). This procedure
      was successfully applied to the study of 1-octacosanol in rat plasma samples
      after a single oral administration (40 mg/kg) of policosanol.

PMID- 11589458
TI  - Determination of metformin in human plasma by high-performance liquid
      chromatography with spectrophotometric detection.
AB  - A simple, selective, sensitive and precise high-performance liquid
      chromatographic plasma assay for the hypoglycemic agent metformin is described.
      Acidified samples of plasma were deproteinated with acetonitrile, washed with
      dichloromethane and the resulting supernatant injected. Chromatography was
      performed at 40 degrees C by pumping a mobile phase of acetonitrile (250 ml) in
      pH 7, 0.03 M diammonium hydrogen phosphate buffer (750 ml) at a flow-rate of 1
      ml/min through a silica column. Metformin and the internal standard (atenolol)
      were detected at 240 nm and were eluted 7.8 and 6.8 min, respectively, after
      injection. No endogenous substances were found to interfere. Calibration curves
      were linear (r>0.999) from 10 to 2000 ng/ml. The absolute recovery of both
      metformin and atenolol was greater than 76%. The detection limit and limit of
      quantitation were 2.5 and 10 ng/ml, respectively. The intra- and inter-day
      precision (C.V.) was 12%, or less, and the accuracy was within 6.2% of the
      nominal concentration. This method is suitable for clinical investigation and
      monitoring metformin concentration.

PMID- 11589460
TI  - Analysis of volatile sulphur compounds in breath by gas chromatography-mass
      spectrometry using a three-stage cryogenic trapping preconcentration system.
AB  - A method for the determination of trace volatile sulphur compounds (VSCs)
      including methanethiol, dimethyl sulfide (DMS) and dimethyl disulfide (DMDS) at
      low ppbv (volume/volume) in breath has been developed using a large volume
      preconcentration technique prior to capillary GC-MS analysis. The breath sample
      was collected in a 6-1 fused-silica-lined stainless steel canister and introduced
      into the three-stage cryogenic trapping preconcentration system by GC-MS in the
      total ion monitoring (scan) mode. The water condensation effect of breath sample
      inside the canister, which is due to the difference between human body
      temperature and laboratory temperature, was examined. The condensed water in the
      fused-silica-lined canister at 24 degrees C did not affect the recoveries of VSCs
      within 12 h. As this three-stage cryogenic trapping preconcentration technique
      made it possible to remove excess water [relative humidity (RH) >95%] and carbon
      dioxide (3.8%) without loss of the VSCs, more than 400 ml of the breath sample
      could be concentrated. The detection limits of methanethiol, DMS and DMDS in a
      breath sample using this method were 0.13, 0.09 and 0.15 ppbv, respectively.

PMID- 11589459
TI  - Reversed-phase high-performance liquid chromatography procedure for the
      simultaneous determination of S-adenosyl-L-methionine and S-adenosyl-L
      homocysteine in mouse liver and the effect of methionine on their concentrations.
AB  - An improved reversed-phase high-performance liquid chromatography (HPLC)
      procedure with ultraviolet detection is described for the simultaneous
      determination of S-adenosyl-L-methionine (SAM) and S-adenosyl-L-homocysteine
      (SAH) in mouse tissue. The method provides rapid resolution of both compounds in
      a 25-microl perchloric acid extract of the tissue. The limits of detection in 25
      microl injection volumes were 22 and 20 pmol for SAM and SAH, respectively. The
      limits of quantitation in 25-microl injection volumes were 55 and 50 pmol for SAM
      and SAH, respectively, with recovery consistently >98%. The assay was validated
      over linear ranges of 55-11000 pmol for SAM and 50-10000 pmol for SAH. The intra
      day precision and accuracy were < or =6.4% relative standard deviation (RSD) and
      99.9-100.0% for SAH and < or =6.7% RSD and 100.0-100.1% for SAM. The inter-day
      precision and accuracy were < or =5.9% RSD and 99.9-100.6% for SAH and < or =7.0%
      RSD and 99.5-100.1% for SAM. Compared to earlier procedures, the HPLC method
      demonstrated significantly better separation, detection limit and linear range
      for SAM and SAH determination. The assay demonstrated applicability to monitoring
      in mice the time-course of the effect of methionine on SAM and SAH levels in the
      liver. Administering methionine to mice increased by 10-fold the liver
      concentration of SAM and SAH within 2 h, which then rapidly decreased to the
      control levels by 8 h. This indicated that methionine was promptly converted to
      SAM and then rapidly catabolized into SAH. Thus, the metabolism of methionine to
      SAM should be considered in the supplementation of methionine to maintain SAM
      levels in the body.

PMID- 11589461
TI  - Two-step chromatographic purification of recombinant Plasmodium falciparum
      circumsporozoite protein from Escherichia coli.
AB  - The Plasmodium falciparum circumsporozoite (PfCS) protein (aa 19-405) has been
      cloned and expressed in E. coli. The protein was purified in a two-step process
      that was rapid and reproducible. E. coli cells were grown to a high density
      before induction for 1 h. Cells were disrupted by high pressure microfluidization
      and the total bacterial protein solubilized in 6 M Gu-HCl. The protein was
      refolded while bound to Ni-NTA agarose by exchange of 6 M Gu-HCl for 8 M urea and
      then slow removal of the urea. The eluted protein was further purified on Q
      Sepharose Fast Flow using conditions developed to remove E. coli proteins and
      reduce endotoxin (to 10 EU/50 microg). Yield was 20 mg of PfCS protein from 10 g
      of wet cell paste. The final protein product bound to HepG2 liver cells in
      culture and inhibited the invasion of those cells by sporozoites in an ISI assay
      greater than 80% over control cultures when used at 10 microg/ml.

PMID- 11589462
TI  - Enantioselective assay of nisoldipine in human plasma by chiral high-performance
      liquid chromatography combined with gas chromatographic-mass spectrometry:
      applications to pharmacokinetics.
AB  - Nisoldipine, a second-generation dihydropyridine calcium antagonist, is a
      racemate compound used in the treatment of hypertension and coronary heart
      disease. This study presents an enantioselective HPLC-GC-MS method for the
      analysis of nisoldipine in human plasma and establishes confidence limits for its
      application to pharmacokinetic studies. Plasma samples were basified and
      extracted with toluene. The enantiomers were resolved on a Chiralcel OD-H column
      using hexane-ethanol (97.5:2.5, v/v) and the (+)- and (-)-fractions were
      collected separately with the diode array detector switched off. For the
      quantification of the nisoldipine enantiomers a GC-MS with an Ultra 1 Hewlett
      Packard column was used with the detector operated in the single-ion monitoring
      mode with electron-impact ionization (m/z 371.35 and 270.20 for nisoldipine and
      m/z 360.00 for the internal standard, nitrendipine). The method proved to be
      suitable for pharmacokinetic studies based on the low quantification limit (0.05
      ng/ml for each enantiomer) and the broad linear range (0.05-50.0 ng/ml for each
      enantiomer). Low coefficients of variation (<15%) were demonstrated for both
      within-day and between-day assays. No interference from drugs associated with
      nisoldipine treatment was observed. The enantioselective pilot study on the
      kinetic disposition of nisoldipine administered in the racemic form to a
      hypertensive patient using a multiple dose regimen revealed the accumulation of
      the (+)-enantiomer with an AUC(0-24) (+)/(-) ratio of approximately 8. Both
      enantiomers were quantified in plasma at a time interval of 24 h. This HPLC-GC-MS
      method is reliable, selective and sensitive enough to be used in clinical
      pharmacokinetic studies on the enantioselective disposition of nisoldipine in
      humans.

PMID- 11589463
TI  - Development of a high throughput 96-well plate sample preparation method for the
      determination of trileptal (oxcarbazepine) and its metabolites in human plasma.
AB  - A high throughput preparation method for the determination of trileptal
      (oxcarbazepine, OXC) and its mono (MHD) and dihydroxy (DHD) metabolites in human
      plasma, using 96-well plate technology, has been developed and validated
      according to international regulatory requirements. Preparation of plasma samples
      (50 microl) containing the compounds to be analysed involved solid-phase
      extraction (SPE) on Empore C18 96-well SPE plates. Eluates from the plate were
      injected onto a reversed-phase column (Hypersil C18,3 microm) with UV detection
      at 210 nm. Detector response was linear over the ranges 0.2-10, 0.1-200 and 0.1
      20 micromol/l, for OXC, MHD and DHD, respectively, with relative standard
      deviations from 1 to 10% and mean accuracies within 4% of the nominal values
      (number of standard curves=3 in duplicate). The limits of quantitation were 0.2,
      0.1 and 0.1 micromol/l, respectively. The overall mean accuracies ranged from 96
      to 106% and precision was in the range 4 to 11%. Cross validation indicated no
      significant difference between plasma concentrations obtained using the 96-well
      method and the previous method using a traditional SPE method with a 50 mg C18
      cartridge. About a threefold increase in sample throughput and a twofold decrease
      of plasma volume required for the assays, were the main advantages obtained from
      the previous method. The method was applied for the determination of 3000 plasma
      samples from clinical studies.

PMID- 11589464
TI  - Determination of free aspartic acid enantiomers in rat brain by capillary
      electrophoresis with laser-induced fluorescence detection.
AB  - Quantification of aspartic acid enantiomers in rat brain by using a chiral
      capillary electrophoresis procedure is described. Amino acids were pre-column
      derivatized with naphthalene-2,3-dialdehyde. Enantiomeric separation was achieved
      by micellar electrokinetic chromatography in the presence of methanol and beta
      cyclodextrin as chiral selector. The chiral separation was coupled with laser
      induced fluorescence detection. Contents of D- and L-aspartic acids in rats at
      different stages of growth (from 1 day before birth to 90 days after birth) were
      determined. D-Aspartic acid was detected in all the brain tissue samples tested,
      but at different levels. In the cerebrum of rats 1 day before birth, D-aspartic
      acid was found to be at the highest concentration of 81 nmol/g wet tissue. The
      level of D-aspartic acid in rat brain falls rapidly after birth, while the L
      aspartic acid level increases with age.

PMID- 11589465
TI  - Evaluation of frontal chromatograms.
AB  - Frontal chromatograms were investigated at low effluent concentrations, and
      deviations from the pertinent theory of chromatography were found in that region.
      These deviations are explained by a prerun in the column occurring between column
      wall and adjacent vertical particle layer. A model was devised for adapting these
      deviations to a mathematical function. According to that model, frontal
      chromatograms have an additional inflection point at low effluent concentrations
      with coordinates defined by the geometry of the column and the particles of the
      column bed. These coordinates are only altered by a packing density leading to
      particle distortion; on the premises of a reproducible column packing, these
      values are neither affected by kinetic parameters nor by a deterioration of the
      active particle surface. The experimental verification shows that the model can
      be employed to describe frontal chromatograms up to the second inflection point,
      when the effluent concentration reaches half of the feed concentration. A
      technical application is indicated in the paper.

PMID- 11589466
TI  - Separation and determination of podophyllum lignans by micellar electrokinetic
      chromatography.
AB  - A micellar electrokinetic chromatography method was established for the
      quantitative analysis of seven podophyllum lignans in Podophyllum emodi Wall.
      var. chinesis sprague. The optimum buffer system was 10 mM NaH2PO4-5 mM borate
      100 mM sodium dodecylsulfate-30% isopropanol (pH 7.20). Voltage was 18 kV and
      detection at 214 nm. The second derivative chromatogram was used to determine a
      low-content component and those not fully separated from adjacent ones. The RSD
      values of migration times and peak areas were <2.2 and <5.5%, respectively. The
      effects of several CE parameters on the resolutions were studied systematically.

PMID- 11589467
TI  - Stir bar sorptive extraction applied to the determination of dicarboximide
      fungicides in wine.
AB  - The dicarboximide fungicides vinclozolin, iprodione and procymidone were analyzed
      in white wines using stir bar sorptive extraction (SBSE) in combination with
      thermal desorption-capillary GC-MS analysis (TD-cGC-MS). The method was optimized
      using spiked water samples in a concentration range between 0.5 and 100 microg/l.
      Iprodione was measured as its degradation product 3,5-dichlorophenyl hydantoin.
      Limits of quantification in the full scan MS mode are 0.5 microg/l for
      vinclozolin and procymidone and 5 microg/l for iprodione. In the ion monitoring
      mode, concentrations 100 times lower can be dosed. Because of wine matrix effects
      on the recoveries, quantification of the target fungicides in wine had to be
      carried out by standard addition. For the thermolabile iprodione, the accuracy of
      SBSE-TD-cGC-MS was verified using SBSE followed by liquid desorption and analysis
      by liquid chromatography-atmospheric pressure chemical ionization mass
      spectroscopy. Procymidone and iprodione were detected in wines in concentrations
      up to 65 microg/l while the highest concentration of vinclozolin detected was
      smaller than 3 microg/l.

PMID- 11589468
TI  - Characterization and modeling of monolithic stationary phases: application to
      preparative chromatography.
AB  - A methodology for characterizing and modeling preparative separations on
      monolithic ion-exchange stationary phases is presented. A dimensionless group
      analysis was carried out to determine the relative importance of mass transfer
      and kinetic resistances on this stationary phase. In contrast to conventional
      beaded morphologies, the continuous bed stationary phase was found to possess
      enhanced mass transport properties resulting in kinetic resistance as the
      dominant non-ideality. Accordingly, a reaction-dispersive steric-mass action
      formalism was successfully utilized for simulating preparative displacement
      chromatography on this resin. Since kinetics were found to be important on this
      column morphology, mobile phase salt concentration was found to be an important
      variable during displacement chromatography on this stationary phase. An increase
      in the mobile phase salt concentration was found to significantly improve the
      displacement separation of a model protein mixture. The formalism presented in
      this paper provides a better understanding of preparative chromatography in
      monolithic resin systems and a means of simulating separations on this class of
      chromatographic stationary phases.

PMID- 11589469
TI  - Preparation of highly selective stationary phases for high-performance liquid
      chromatographic separation of enantiomers by direct copolymerization of monomers
      with single or twin chiral ligands.
AB  - Uniformly sized macroporous polymer beads, which can be used as chiral stationary
      phase (CSP), have been prepared by the staged templated suspension polymerization
      process using chiral monomer as one of the copolymerization components. This
      approach enables the preparation of CSPs for which properties such as pore size,
      pore volume, surface area, chemistry, and chiral ligands can be tuned over a
      broad range. Several types of well-defined chiral monomers were prepared and
      allowed to assess synergistic effect of multiple selectors attached to a branched
      linker as well as the effect of the length and chemistry of the linker.
      Microscale batch screening was used for simple and rapid evaluation of
      selectivity. The most promising candidate CSPs were prepared on a larger scale
      and packed into HPLC columns. Their performance was demonstrated on the
      separation of racemic N-(3,5-dinitrobenzoyl)-alpha-amino acid alkylamides. The
      highest separation factors alpha of up to 27 were observed for CSPs prepared from
      monomers containing the branched spacer. These highly selective CSPs also enabled
      the separation of larger amounts of the target racemates upon column overload
      conditions.

PMID- 11589470
TI  - Ultra-short columns and ballistic gradients: considerations for ultra-fast
      chromatographic liquid chromatographic-tandem mass spectrometric analysis.
AB  - Ultra-fast chromatographic separations has enabled fast chromatographic method
      development and rapid analysis for sample quantification. Decreasing over-all
      analytical time has become a factor of major importance for all aspects of drug
      discovery. However, merely decreasing chromatographic analysis time by decreasing
      k' can lead to inconsistent quantitative or qualitative results due to
      ineffective separations in complex matrices. We have found that by changing
      column length and gradient slope we can maintain chromatographic integrity of
      chemically diverse analytes and achieve the analytical speed required for
      bioanalytical drug discovery quantitative analysis. We have optimized method
      development strategy by performing separations on 2x20 mm HPLC columns at flow
      rates of 1.5 ml/min to 2 ml/min with full linear gradients achieved in 1 min for
      the quantification of pharmaceuticals and their metabolites from biological
      matrices. This method development strategy can be readily adapted to other
      matrices. This paper will discuss the effects of column length and gradient time
      in ultra-fast chromatographic resolution.

PMID- 11589471
TI  - Determination of polycyclic aromatic hydrocarbons by liquid chromatography
      electrospray ionization mass spectrometry using silver nitrate as a post-column
      reagent.
AB  - Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) using
      silver nitrate as a post-column reagent has been used for the determination of 10
      polycyclic aromatic hydrocarbons (PAHs) in river water. In this method, after all
      the PAHs were separated by reversed-phase liquid chromatography, analytes formed
      complexes with silver cation by mixing with silver nitrate solution. The
      complexes then transfer the molecular ion, [M]+, of the PAHs by charge transfer
      using in source collision-induced dissociation. The positive ion ESI mass spectra
      of all PAHs tested in this study showed [M]+ as the base peak and abundant
      [M+Ag]+, [2M+Ag]- with very weak or no [2M+Ag]+. For the sample extraction,
      several solid-phase extraction parameters using the blue-chitin column were
      optimized. The limits of detection (S/N=3) of all PAHs for the spiked river water
      sample ranged from 0.001 to 0.03 ng/ml, and the detector responses were linear up
      to I ng/ml (correlation coefficients > or =0.0998). Repeatability and
      reproducibility were in the range from 4.3 to 6.8% and from 6.2 to 9.5%,
      respectively.

PMID- 11589472
TI  - Identification and quantification of major bovine milk proteins by liquid
      chromatography.
AB  - In the field of food quality, bovine milk products are of particular interest due
      to the social and economic importance of the dairy products market. However, the
      risk of fraudulent manipulation is high in this area, for instance, replacing
      milk powder by whey is very interesting from an economic point of view.
      Therefore, there is a need to have suitable analytical methods available for the
      determination of all milk components, which is currently not the case, especially
      for the main proteins. The detection of potential manipulations requires then a
      clear analytical characterisation of each type of bovine milk, what constitutes
      the goal of this work. The separation of the major milk proteinic components has
      been carried out by ion-pair reversed-phase HPLC with photodiode array detection,
      using a C4 column. The overall optimisation has been achieved using a statistical
      experimental design procedure. The identification of each protein was ascertained
      using retention times, peak area ratios and second derivative UV spectra.
      Quantification was based on calibration curves drawn using purified proteins.
      Major sources of uncertainty were identified and the full uncertainty budget was
      established. The procedure was initially developed using the skimmed milk powder
      certified reference material CRM 063R and then applied to various types of
      commercial milks as well as to raw milk. The method is able to separate and
      quantify the seven major proteins (K-casein, alphas2-casein, alphas1-casein, beta
      casein, alpha-lactalbumin, beta-lactoglobulin B and beta-lactoglobulin A) in one
      run and also to provide precise determinations of the total protein
      concentration. These are important results towards the further development of a
      reference method for major proteins in milk. In addition, the use of a certified
      material reference is suggested in order to make comparisons of method
      performances possible.

PMID- 11589473
TI  - Determination of folates in foods by high-performance liquid chromatography with
      fluorescence detection after precolumn conversion to 5-methyltetrahydrofolates.
AB  - A liquid chromatographic-fluorimetric determination of folates in foodstuffs
      including their extraction, without or with deconjugation, chemical conversion to
      5-CH3-H4PteGlu(n) and purification of the extract by affinity chromatography is
      reported. The conversion enables the analysis of total folates and also of the
      contents of the different mono- and polyglutamate forms of the folates. The
      method has a satisfactory day-to-day repeatability (never,more than 10%) and a
      very low detection limit (0.02 pmol per injection). Depending on the folate
      studied, the recovery rates varied from 78% (10-CHO-PteGlu) to 98% (5-CHO
      H4PteGlu). Furthermore it has been possible to show that the deconjugation of the
      folates by rat plasma conjugase was incomplete in foodstuffs whereas chicken
      pancreas conjugase effectively converted the different folate polyglutamates into
      folate diglutamates. It could not be demonstrated that prior hydrolysis with a
      protease and amylase was useful for the analysis of the different foodstuffs
      studied (yeast, spinach, beef liver, beef fillet and peas) when deconjugation was
      performed with the chicken pancreas conjugase.

PMID- 11589474
TI  - Determination of actinides in environmental and biological samples using high
      performance chelation ion chromatography coupled to sector-field inductively
      coupled plasma mass spectrometry.
AB  - High-performance chelation ion chromatography, using a neutral polystyrene
      substrate dynamically loaded with 0.1 mM dipicolinic acid, coupled with sector
      field inductively coupled plasma mass spectrometry has been successfully used for
      the separation of the actinides thorium, uranium, americium, neptunium and
      plutonium. Using this column it was possible to separate the various actinides
      from each other and from a complex sample matrix. In particular, it was possible
      to separate plutonium and uranium to facilitate the detection of the former free
      of spectral interference. The column also exhibited some selectivity for
      different oxidation states of Np, Pu and U. Two oxidation states each for
      plutonium and neptunium were found, tentatively identified as Np(V) and Pu(III)
      eluting at the solvent front, and Np(IV) and Pu(IV) eluting much later. Detection
      limits were 12, 8, and 4 fg for 237Np, 239Pu, and 241Am, respectively, for a 0.5
      ml injection. The system was successfully used for the determination of 239Pu in
      NIST 4251 Human Lung and 4353 Rocky Flats Soil, with results of 570+/-29 and
      2939+/-226 fg g(-1), respectively, compared with a certified range of 227-951 fg
      g(-1) for the former and a value of 3307+/-248 fg g(-1) for the latter.

PMID- 11589475
TI  - Use of porous glass and silica gel as support media of a surface compound for
      generation of analytes in gaseous standard mixtures. New method for the
      determination of the amount of analyte generated.
AB  - The paper presents a new method for the determination of a volatile component of
      a gaseous standard mixture obtained by thermal decomposition of a suitable
      surface compound. The amount of the analyte generated (under given conditions of
      thermal decomposition) per unit of mass of the chemically modified material has
      been determined exclusively on the basis of measuring generation time. Therefore,
      the total error of the determination of the amount of a standard compound depends
      solely on the respective errors of weighing the material and measuring its
      decomposition time (both being direct measurements). This new method permits
      obtaining a few measuring points on the basis of a single sample of the material
      with chemically modified surface.

PMID- 11589476
TI  - Host immune reactivity and antifungal chemotherapy: the power of being together.
AB  - Fungal infections, particularly those in immunocompromised hosts, have been a
      major therapeutic challenge over recent decades. The difficulty in diagnosing
      invasive infections, together with the emergence of unusual opportunistic
      pathogens and a pathogen shift in the spectrum of the causative organisms, have
      greatly hampered the effectiveness of antifungal therapy. Knowledge of the
      immunoregulation of fungal infections may provide new insights for therapeutic
      interventions. The appreciation of the importance of T helper cells and cytokines
      in the overall coordination of the effector immune response to fungi has offered
      novel opportunities to manipulate these processes and to alter the outcome of
      fungal infections while improving the therapeutic efficacy of antifungal drugs.
      Cytokine and cytokine antagonists, alone or in combination with antifungals, have
      the potential to overcome the specific defects of host immune reactivity
      predisposing to fungal infections. The current challenge lies in translating much
      of the information obtained in experimental and preclinical studies into
      therapeutic strategies providing prospects for the ultimate treatment of fungal
      infections.

PMID- 11589477
TI  - The role of nebulized antibiotics in treating serious respiratory infections.
AB  - The administration of a nebulized antibiotic in serious respiratory tract
      infections ensures high antibiotic concentrations at the site of infection,
      minimising systemic concentrations and their resultant risk of toxicity.
      Nebulized antibiotics have been used for the treatment of chronic infection with
      Pseudomonas aeruginosa, particularly in cystic fibrosis, but with variable
      clinical efficacy. Antibiotic delivery by nebulization is greatly influenced by
      the product formulation and the nebulizer. Use of intravenous formulations via a
      nebulizer can lead to exposure to potentially irritant or toxic additives and
      inappropriate pH or osmolality ranges, whilst the choice of nebulizer can greatly
      influence the drug deposition in the airway. Tobramycin Nebulizer Solution (TNS)
      is the first specific formulation for nebulization in cystic fibrosis using a
      designated nebulizer. The potential extrapolation of nebulized antibiotic therapy
      to other serious respiratory infections, in particular bronchiectasis and
      ventilator-associated pneumonia, is explored in this review.

PMID- 11589478
TI  - In vitro evaluation of ertapenem (MK-0826), a long-acting carbapenem, tested
      against selected resistant strains.
AB  - Ertapenem (MK-0826) is a novel, long-acting parenteral carbapenem. The purpose of
      this in vitro study was to test ertapenem's activity against a collection of
      multiply-resistant strains of gram-positive and -negative bacteria isolated from
      locations worldwide, and to examine its bactericidal activity and ability to act
      in a synergistic manner in combination with other antimicrobial agents. Ertapenem
      was active against a variety of gram-negative pathogens, with particular potency
      noted for Escherichia coli and Klebsiella pneumoniae (MIC90s < or =0.015-0.5
      microg/mL) including extended spectrum beta-lactamase producing strains. Less
      ertapenem activity was seen against Pseudomonas aeruginosa, especially
      ceftazidime-resistant strains (MIC50 16 microg/mL). Except for enterococci,
      ertapenem was active against most gram-positive species, including beta
      haemolytic streptococci (MIC90 0.03 microg/mL; 100% susceptible), viridans group
      streptococci (MIC90 2 microg/mL; 98.1% susceptible), and penicillin-susceptible
      Streptococcus pneumoniae (MIC90 < or =0.015 microg/mL; 100% susceptible).
      Ertapenem was also very potent against Haemophilus influenzae (MIC90 0.25
      microg/mL; 100% susceptible). Bactericidal action was observed versus
      staphylococci, E. coli, and K. pneumoniae, and at least an additive effect was
      detected against the majority of the strains tested when ertapenem was combined
      with ciprofloxacin or gentamicin. These results from testing 902 organisms
      indicate that ertapenem appears to be a promising broad-spectrum carbapenem with
      a possible role against some emerging resistant species.

PMID- 11589479
TI  - In vitro activity of tea tree oil against Candida albicans mycelial conversion
      and other pathogenic fungi.
AB  - The antifungal activity of Melaleuca alternifolia Maiden (Myrtaceae) essential
      oil against yeasts (Candida spp., Schizosaccharomyces pombe, Debaryomyces
      hansenii) and dermatophytes (Microsporum spp. and Tricophyton spp.) is reported.
      We focused on the ability of tea tree oil to inhibit Candida albicans conversion
      from the yeast to the pathogenic mycelial form. Moreover we carried out broth
      microdilution test and contact tests to evaluate the killing time. M.
      alternifolia essential oil inhibited the conversion of C. albicans from yeast to
      the mycelial form at a concentration of 0.16% (v/v). The minimum inhibitory
      concentrations (MICs) ranged from 0.12% to 0.50% (v/v) for yeasts and 0.12% to 1%
      (v/v) for dermatophytes; the cytocidal activity was generally expressed at the
      same concentration. These results, if considered along with the lipophilic nature
      of the oil which enables it to penetrate the skin, suggest it may be suitable for
      topical therapeutic use in the treatment of fungal mucosal and cutaneous
      infections.

PMID- 11589480
TI  - Saquinavir up-regulates telomerase activity in lymphocytes activated with
      monoclonal antibodies against CD3/CD28.
AB  - The present study describes the effect of the HIV protease inhibitor saquinavir
      on telomerase activity and interferon-gamma (IFN-gamma) production of nonadherent
      mononuclear cells (NA-MNC). Cells obtained from peripheral blood of healthy
      donors were exposed in vitro to a mixture of monoclonal antibodies against CD3
      and CD28 membrane antigens in order to activate prevalently T cell subsets.
      Treatment with saquinavir was performed at the time of cell stimulation.
      Thereafter, NA-MNC were tested for telomerase activity (TRAP assay) and
      interferon-gamma production up to 7 days later. The results show that saquinavir
      up-regulates telomerase activity and IFN-gamma release in activated NA-MNC. These
      observations suggest that the anti-HIV effects of saquinavir could be accompanied
      by other immunopharmacological properties, influencing some aspects of the
      functional activity of immunocompetent cells. These include possible antagonistic
      effects against lymphocyte senescence, through telomerase activation, and a
      potentiating activity on the production of IFN-gamma following T cell activation.

PMID- 11589481
TI  - Gentamicin concentrations in urine, cortex and medulla in an acutely obstructed
      kidney animal model.
AB  - Gentamicin was administered intraperitoneally, three times in 12 h to Hartley
      type guinea-pigs which had undergone complete unilateral ureteral obstruction
      with normal contralateral ureteral function for either 24 hours, 7 days or 21
      days. Two hours after the last drug dose urine samples were collected from
      urinary bladder and obstructed ureter. Healthy and obstructed kidneys were then
      surgically removed from all sacrificed animals. Gentamicin concentration in urine
      of healthy kidney was 112-266 microg/ml, and in obstructed kidney 18-53
      microg/ml, with a tendency of linear decrease over a 3-week obstruction period.
      The gentamicin concentration in obstructed renal cortex never exceeded one-third
      of the gentamicin concentration in unobstructed renal cortex. The maximum
      gentamicin concentration in obstructed renal medulla was 75% of the gentamicin
      concentration in unobstructed renal medulla.

PMID- 11589482
TI  - Temporary interruption of ceftazidime continuous infusion without reduction of
      activity: a computer-assisted simulation.
AB  - Continuous infusion (CI) of ceftazidime has been demonstrated to add clinical
      advantages in the treatment of infection of neutropenic cancer patients,
      especially in the presence of gram-negative bacteremia. However, this particular
      administration route is not always feasible in this particular clinical setting
      because of the patient's need of additional care or drug administration. The aim
      of this study was to evaluate, through a computer-assisted simulation, the
      modifications of drug concentration in presence of a single or repeated 2-hour
      interruptions of CI ceftazidime in critically ill patients. Our analysis shows
      that a loading dose of 20 mg/kg, followed by a CI of 100/mg/kg/die, should be
      able to maintain efficacious plasma concentrations in all subjects, even when it
      is interrupted for a 2-hour period every 8 hours. Plasma concentrations after
      interruption should not fall below 8 microg/mL and for about 65-80% of time
      should reach levels equal to 5 times the MIC of the infecting pathogen. A 2-hour
      interruption of CI ceftazidime up to 3 times a day is likely to represent a safe
      and efficacious administration regimen that may enhance the management of the
      treatment of infectious complications in critically ill patients such as
      neutropenic cancer patients.

PMID- 11589483
TI  - Rationale for treating community-acquired lower respiratory tract infections with
      amoxicillin/sulbactam combination through pharmacodynamic analysis in the setting
      of aminopenicillin-resistant organisms.
AB  - In order to establish a rationale for treating community-acquired lower
      respiratory tract infections, we assess here the pharmacodynamics of
      amoxicillin/sulbactam, 500mg/500mg, a formulation marketed in Argentina since
      1988 and currently available in 17 countries, against the major pathogens, in
      comparison with that of a novel formulation (875mg/125mg, see J Chemother 2000;
      12: 223-227). In time-kill studies, both bactericidal and inhibitory activity
      were seen in the 1.5- and 6-h sera, obtained from 12 volunteers after a single
      oral dose, against both a penicillin-susceptible and an -intermediate
      Streptococcus pneumoniae strain, as well as against Moraxella catarrhalis and a
      beta-lactamase-negative Haemophilus influenzae strain. Only the 1.5-h sera proved
      bactericidal against a penicillin-resistant S. pneumoniae strain (MIC, 2
      microg/ml) and a beta-lactamse-positive H. influenzae isolate. This study
      suggests that amoxicillin/sulbactam (500mg/500mg) is still a suitable option for
      treating community-acquired lower respiratory tract infections, allowing a b.i.d.
      dosing schedule. Caution should be taken with pneumonia caused by beta-lactamase
      positive H. influenzae or penicillin-resistant (MIC > or =2 microg/ml) S.
      pneumoniae isolates. Either shorter dosing intervals (t.i.d.) or a higher
      amoxicillin content in the formulation (i.e. 875 mg) may be required in these
      situations.

PMID- 11589484
TI  - Pulmonary disposition of lomefloxacin in patients with acute exacerbation of
      chronic obstructive pulmonary disease. A multiple-dose study.
AB  - In this study we have measured the concentrations of lomefloxacin at steady state
      in serum and in the intrapulmonary region at specified intervals for 24 h
      following administration of the last dose of drug in patients suffering from
      acute exacerbation of chronic obstructive pulmonary disease (COPD). Twenty
      subjects were enrolled. They received lomefloxacin 400 mg orally once-daily for 5
      consecutive days. All patients were divided into five groups, with 4 subjects in
      each group, according to sampling times (2, 4, 8, 12, and 24 h after the last
      dose). At bronchoscopy, bronchial biopsies and bronchoalveolar lavage (BAL) were
      performed. At 12 h after the last dose, serum concentration of lomefloxacin was
      >1.0 microg/mL and at 24 h it was still detectable, but, at all times, the
      concentrations in bronchial secretion, bronchial mucosa, and epithelial lining
      fluid (ELF) were greater than the concentrations in serum [bronchial secretions
      (pg/mL) = 2.5+/-1.2; 2.2+/-1.0: 2.0+/-1.1; 1.8+/-1.1; 0.6+/-0.3. bronchial mucosa
      (microg/g) = 5.9+/-2.1; 6.2+/-1.8; 2.6+/-2.2; 1.9+/-1.5; 1.0+/-0.9. ELF
      (microg/mL) = 6.9+/-2.8; 5.9+/-2.6; 3.1+/-1.9; 2.2+/-1.0; 0.8+/-1.3. serum
      (microg/mL) = 3.2+/-1.4; 2.8+/-0.9: 2.1+/-1.5; 1.2+/-1.1; 0.4+/-0.81. We must
      stress that we observed a large inter-individual variability in concentrations.
      Our data show that lomefloxacin once-daily induces high and sustained
      concentrations in the various potential sites of pulmonary infection and clearly
      indicate that the pharmacokinetic behavior of this fluoroquinolone permits once
      daily administration in patients with acute exacerbations of COPD.

PMID- 11589485
TI  - An observational study on the epidemiology of respiratory tract bacterial
      pathogens and their susceptibility to four injectable beta-lactam antibiotics:
      piperacillin, piperacillin/tazobactam, ceftazidime and ceftriaxone.
AB  - Bacterial infections of the respiratory tract account for a large proportion of
      total medical consultations in general practice. In recent years, antibiotic
      resistance has increased alarmingly in a number of bacterial species that are
      common causes of these infections. The aim of this observational study was to
      determine the antibiotic resistance of microbial agents isolated from patients
      with acute or acutely exacerbated respiratory infections. Subjects recruited as
      potential sources of bacteria were either outpatients seen in a number of
      specialized clinics and hospital practices, or hospitalized patients. Overall,
      648 consecutive patients (67% male, mean age 48.1+/-27.0 years) with infection of
      the upper or lower respiratory tract were observed during a 13-month period. A
      total of 551 pathogenic microbial strains were isolated and tested for their in
      vitro susceptibility to piperacillin, piperacillin/tazobactam, ceftazidime, and
      ceftriaxone. Among all isolates, the four most frequent pathogens were
      Pseudomonas aeruginosa (132 isolates, 24%), Streptococcus pyogenes (99 isolates,
      18%), Staphylococcus aureus (93 isolates, 17%), and Klebsiella pneumoniae (46
      isolates, 8%). The susceptibility of gram-positive isolates ranged from 97.5% to
      95.1%, and no remarkable difference was found in the antibacterial activity of
      tested b-lactam antibiotics. The susceptibility of gram-negative isolates to
      piperacillin and piperacillin/tazobactam was also similar: 96.5% and 97.1%,
      respectively. In contrast, differences were found between piperacillin (or
      piperacillin/tazobactam) and either ceftazidime (p=0.003) or ceftriaxone
      (p<0.0003) in gram-negative isolates. We conclude that, despite the extensive use
      of beta-lactam antibiotics (piperacillin, ceftazidime, and ceftriaxone) in
      medical practice during the past three decades, the susceptibility of the most
      common pathogens involved in the etiology of upper and lower respiratory tract
      infections to these antibiotics is still high. In particular, bacterial
      resistance developed by gram-positive organisms against piperacillin is
      negligible and not alarming.

PMID- 11589487
TI  - Persistent fungemia--risk factors and outcome in 40 episodes.
AB  - The aim of this multicenter survey was to assess risk factors and mortality in
      patients with persistent fungemia (PF). Cases of persistent fungemia, defined as
      positive blood culture for at least 3 causative days of antifungal therapy were
      selected. Forty cases of persistent fungemia (lasting more than 3 days) were
      compared with 270 non-persistent fungemias appearing within the same period, and
      analyzed by univariate and multivariate analysis for risk factors and outcome.
      The median number of days of positive culture was 4.4 (3 - 20): 22 episodes were
      due to Candida albicans, 1 due to non-albicans Candida spp., 6 episodes due to
      non-Candida spp. Yeasts: 15 were catheter related, 16 patients had yeast-infected
      surgical wounds, 12 were neutropenic, 4 cases were caused by species resistant in
      vitro, 2 to amphotericin B (Trichosporon spp.) and 2 to fluconazole (C.
      laurentii, C. glabrata). Fifteen patients (37.5%) died, 7 of whom due to
      fungemia. Nineteen cases had one known risk factor (10 had infected wound, 4
      infected vascular catheter, 3 were neutropenic and 2 had inappropriate therapy).
      Fourteen cases had two known risk factors (4 had wound and infected catheter, 4
      neutropenia and infected catheter, 2 neutropenia and resistant organism, 4 other
      combinations. Two cases had 3 known risk factors and one had 4 risk factors for
      persistent fungemia. Artificial ventilation, C. glabrata etiology, non-Candida
      spp. yeasts such as Trichosporon spp. and Cryptococcus spp. and prior surgery
      were significantly associated with persistent fungemia in univariate, whereas
      only C. glabrata etiology in multivariate analysis. Breakthrough fungemia during
      empiric therapy with fluconazole was also observed more frequently in patients
      with persistent fungemia. However, there was no difference in both attributable
      and overall mortality between both groups.

PMID- 11589486
TI  - Quantitative viremia test for early prediction of a biochemical response in
      patients with chronic hepatitis C treated with interferon.
AB  - To evaluate the importance of the changes in viremia as an early predictor of the
      outcome of interferon (IFN) therapy, we assayed the levels of hepatitis C virus
      (HCV)-RNA in stored serum samples obtained from 34 patients with chronic
      hepatitis C who showed different biochemical responses to therapy. Serum samples
      obtained before the start of therapy and after 1 and 3 months were used, and
      viremia levels were determined by "branched DNA (bDNA)" technique. Viremia levels
      at 1 month of therapy were lower than pre-therapy levels in all 19 patients who
      had shown a persistent normalization of ALT during therapy (responder patients).
      The bDNA test was negative, i.e. the levels of viremia were below the sensitivity
      threshold of the method, in 12 (63.1%) patients at 1 month and in 13 (68.4%) at
      the 3rd month of therapy, whereas the bDNA test was negative in none of the 15
      non-responder patients at the 1st month and in only 2 (13.3%) of them at the 3rd
      month of therapy. The bDNA test was superior to the ALT test both in predicting
      the non-response and the biochemical response to IFN after 1 month of therapy.
      The bDNA test results, instead, were not predictive of the duration of the
      response to IFN, either at the 1st or 3rd months of therapy. These results seem
      to indicate the usefulness of measuring the HCV-RNA levels at the beginning and
      after 1 month of IFN therapy in order to envisage or exclude a possible
      biochemical response early on in treatment.

PMID- 11589488
TI  - Three conventional-drug combination (ifosfamide, carboplatin, etoposide--ICE
      regimen) in advanced non-small cell lung cancer (NSCLC).
AB  - Fifty consecutive patients with stage IIIB-IV non-small cell lung cancer (NSCLC)
      received the ICE regimen at intermediate doses (ifosfamide 1 g/m2, carboplatin
      120 mg/m2, etoposide 80 mg/m2, day 1 to 3, q.4 weeks, for a maximum of 6 cycles).
      Overall 2 complete response (CR) and 10 partial response (PR) (overall response,
      OR: 24%, 95% C.I. 14-37%) were observed. An additional 7 patients had stable
      disease (SD) lasting more than 6 months, therefore a clinical benefit (CR+PR+SD
      >6 mos) was achieved in 19 patients (38%). Median time-to-progression (TTP) was 7
      months and median overall survival (OS) was 11 months; 1- and 2-year survival
      rates were 36% and 10%. The ICE regimen was well tolerated and devoid of any
      cardiac, hepatic or neurologic toxicity. Moderate nausea and vomiting were easily
      manageable, grade 2 alopecia was universal, while hematological toxicity was mild
      (grade 2 leuko- and thrombocytopenia). Due to its efficacy and safety profile,
      this 3-drug regimen can be considered for routine community use.

PMID- 11589489
TI  - Perioperative locoregional application of mitoxantrone in patients with early
      breast carcinoma.
AB  - The aim of this study was to investigate the clinical and morphological aspects
      of drug diffusion and efficacy after perioperative locoregional application of
      mitoxantrone in patients with early breast cancer. Mitoxantrone was injected at a
      dose of 0.5 ml (1.0 mg) in two sites around the tumor in 37 patients.
      Intraoperative inspection of mitoxantrone diffusion in breast and axillary
      tissues was carried out by blue color of the chemotherapeutic drug.
      Investigations of reactive morphological changes in axillary nodes were
      determined intraoperatively by blue stained lymph capillaries identified 2-4 cm
      laterally from the application sites and in 30 patients a mean of 1.5 stained
      axillary nodes was found. The light microscopy in the metastatic blue lymph nodes
      showed circulatory changes, dilatation of marginal sinus and inflammatory
      alterations. It was concluded that lymphotropic locoregional application of
      mitoxantrone results in diffusion of the drug in the regional lymph drainage and
      in cytotoxic effects on axillary nodes.

PMID- 11589490
TI  - Turkish primary school students as carriers of group A beta-hemolytic
      streptococci and susceptibility of strains to penicillin and erythromycin.

PMID- 11589491
TI  - Comparison of the ATB fungal method with the NCCLS broth macrodilution method
      (M27-A) for determining susceptibility of Candida clinical isolates.

PMID- 11589492
TI  - Antibiotic susceptibility of Enterobacteriaceae species isolated in Venezuela
      over ten years.

PMID- 11589493
TI  - Developing an optimal sampling design. A case study in a coastal marine
      ecosystem.
AB  - The development of a sampling design for optimising sampling site locations
      collected from a coastal marine environment has been the purpose of the present
      work; application of statistical analysis and spatial autocorrelation methods
      have been carried out. The dataset included data collected from 34 sampling sites
      spaced out in the Strait of Lesbos, Greece, arranged in a 1 x 1 NM grid. The
      coastal shallow ecosystem was subdivided into three zones, an inner one (7
      stations), a middle one (16 stations) and an offshore zone (11 stations). The
      standard error of the chlorophyll-a concentrations in each zone has been used as
      the criterion for the sampling design optimisation, resulting into reallocation
      of the sampling sites into the three zones. The positions of the reallocated
      stations have been assessed by estimation of the spatial heterogeneity and
      anisotropy of chlorophyll-a concentrations using variograms. Study of the
      variance of the initial dataset of the inner zone taking into account spatial
      heterogeneity, revealed two different sub-areas and therefore, the number of the
      inner stations has been reassessed. The proposed methodology eliminates the
      number of sampling sites and maximises the information of spatial data from
      marine ecosystems. It is described as a step-by-step procedure and could be
      widely applied in sampling design concerning coastal pollution problems.

PMID- 11589494
TI  - Monitoring atmospheric metal pollution: a review of the use of mosses as
      indicators.
AB  - This article reviews the literature on the use of mosses for monitoring
      atmospheric metal pollution. It discusses the nature of mosses, the mechanisms
      for moss uptake of metals from the air and wet precipitation, the various forms
      in which mosses are used for this purpose, and cases in which mosses have been
      used for monitoring local hot spots of pollution, and regional patterns of metal
      pollution. Also highlighted are the questions of uptake of metals from the
      substrates, interspecies differences, and a comparison of the effectiveness of
      mosses with other indicator materials, among other issues.

PMID- 11589495
TI  - Limitations of multimedia models for use in environmental decision making.
AB  - The United States currently is engaged in a complex, multi-billion dollar effort
      to cleanup a legacy of both privately- and federally-owned hazardous waste sites.
      Decisions regarding the best approach for remediation of these sites often are
      based on the analysis of potential risks to human health and the environment. A
      cornerstone of such analysis is the frequent use of computerized multimedia
      environmental transport models, to evaluate the large quantities of information
      necessary to understand the present and future implications of contamination at a
      site. One barrier to wide-spread use of this analytical procedure is the view
      that results obtained using computer models are highly dependent on user input,
      and therefore, subject to manipulation. It is widely recognized that for
      decisions to be both credible and implementable, the public must have confidence
      in both the scientific basis for judgments involved and the decision processes
      employed (NRC, 1983). Our purpose in this article is to overview the difficulties
      associated with application of multimedia models to real world problems and the
      contribution these models can make to technically sound estimates of exposure and
      risk.

PMID- 11589496
TI  - Preliminary air pollution monitoring in San Miguel, Buenos Aires.
AB  - Passive diffusion samplers were employed in San Miguel (Buenos Aires Metropolitan
      Area) for a preliminary air pollution monitoring. The highest loads were observed
      in downtown, compared with an urban background site. Total suspended particulate
      matter (TSPM) varied from 0.257 to 0.033 mg cm(-2) month(-1); dust was examined
      for particle nature and size distribution. A similar trend was observed for
      nitrogen dioxide (NO2) and TSPM spatial distribution, suggesting that traffic is
      the major pollution source. Sulphur dioxide (SO2) values were low and rather
      homogeneous. Levels for the investigated pollutants are below EPA's guide line
      values. Geographic (flat area, near to Rio de La Plata) and climatologic factors
      (rainfalls and variable wind directions) contribute to disperse pollutants.

PMID- 11589497
TI  - Metals in feathers of sooty tern, white tern, gray-backed tern, and brown noddy
      from islands in the North Pacific.
AB  - Levels of heavy metals are usually higher in adult than young birds because they
      eat larger, more contaminated prey, or because they have had longer to accumulate
      metals in their tissues. Further, levels of contaminants are usually less in
      birds nesting on remote, offshore islands than in birds breeding closer to
      mainland areas that are urbanized and industrialized. We examined the feather
      levels of arsenic, cadmium, chromium, lead, manganese, mercury, and selenium in
      adult sooty terns (Sterna fuscata), gray-backed terns (Sterna lunata), and brown
      noddy (Anous stolidus, and adult and young white terns (Gygis alba, from Midway
      Atoll, and in adult and young sooty terns and adult brown noddy from Manana
      Island, Hawaii (chicks of other terns were not available). We tested and rejected
      the null hypotheses that metal levels are not significantly different among
      species, ages, and locations. Despite their small size, adult white terns had the
      highest levels of lead, arsenic and tin. Brown noddies had the highest levels of
      cadmium, chromium, manganese, and selenium. Sooty and white terns had the highest
      levels of mercury. Sooty tern adults had significantly higher levels of cadmium,
      mercury, and selenium than young, while young had significantly higher levels of
      arsenic and manganese. White tern adults had significantly higher levels of
      selenium and tin than young, while young had higher levels of cadmium and mercury
      than adults. Except for mercury, there were significant inter-location
      differences within species in all heavy metals. Contrary to expectation, where
      the differences were great, metals generally were higher in the feathers of terns
      and noddies from Midway than from Manana.

PMID- 11589498
TI  - Application of intrawell testing of RCRA groundwater monitoring data when no
      upgradient well exists.
AB  - A statistical quality control approach to detect changes in groundwater quality
      from a regulated waste unit is described. The approach applies the combined
      Shewhart-CUSUM control chart methodology for intrawell comparison of analyte
      concentrations over time and does not require an upgradient well. A case study
      from the U.S. Department of Energy's Hanford Site is used for illustration
      purposes. This method is broadly applicable in groundwater monitoring programs
      where there is no clearly defined upgradient location, the groundwater flow rate
      is exceptionally slow, or where a high degree of spatial variability exists in
      parameter concentrations. This study also indicates that the use of the Data
      Quality Objectives (DQO) process can assist in designing an efficient and cost
      effective groundwater monitoring plan to achieve the optimum goal of both low
      false positive and low false negative rates (high power).

PMID- 11589499
TI  - Synergy between ascorbate and alpha-tocopherol on fibroblasts in culture.
AB  - Ascorbate and tocopherol are important antioxidants that protect cells against
      oxidative stress. The interaction of ascorbate and alpha-tocopherol in cells is
      difficult to detect as both ascorbate and alpha-tocopherol are unstable in vitro
      in a biological medium. We examined the interactions between human dermal
      fibroblasts, ascorbate and alpha-tocopherol to determine the effects of the
      vitamins on growth and cell viability. The interaction of ascorbate and alpha
      tocopherol was studied in a fibroblast culture medium during 48h. Ascorbate and
      alpha-tocopherol were detected by fluorimetry after high-performance liquid
      chromatography (HPLC). Cell growth and cell viability were studied by cell
      numeration after trypan blue staining. The ascorbate concentration fell in
      presence of alpha-tocopherol in cell culture medium under all experimental
      conditions, with or without cells. Ascorbate partly protected alpha-tocopherol
      but only in presence of cells. Cell viability was preserved by alpha-tocopherol
      whereas ascorbate enhanced fibroblast growth. The synergy between ascorbate and
      alpha-tocopherol corresponds to a consumption of ascorbate which spares alpha
      tocopherol but only in presence of cells.

PMID- 11589500
TI  - Ovalbumin sensitization of guinea-pigs reduces fMLP-induced calcium signal in
      alveolar macrophages.
AB  - In this study we analyzed the N-formyl-Met-Leu-Phe (fMLP)-induced calcium signal
      in alveolar macrophages (AM) isolated from ovalbumin-sensitized (OA-sensitized
      AM) and naive (naive AM) guinea-pigs. Guinea-pigs were sensitized by subcutaneous
      injection of OA and AM were isolated by bronchoalveolar lavage 6 weeks
      thereafter. On the following day, we measured in resting and fMLP-stimulated
      cells: intracellular calcium concentration by fura-2 imaging analysis, forskolin
      induced cyclic AMP production and superoxide dismutase inhibitable superoxide
      anion release of adherent AM. Resting calcium was 82+/-5.0 nM (n=217) and 144+/
      9.3 nM (n=213, P<0.001) in naive and OA-sensitized AM respectively. fMLP (10(-11)
      10(-7)M) induced a dose-dependent calcium increase, 10(-8)M being the maximal
      effective dose in both naive and OA-sensitized AM. However, at all doses tested,
      this fMLP effect was lower in OA-sensitized than in naive AM. While in resting
      condition 10(-5)M forskolin increased cyclic AMP both in naive and OA-sensitized
      AM, in fMPL-stimulated AM forskolin was effective only in OA-sensitized AM.
      Superoxide anion release measured 10 min after fMLP stimulus was higher in naive
      than in sensitized AM. These data suggest that the fMLP-induced intracellular
      signal is different in OA-sensitized AM compared to naive cells.

PMID- 11589501
TI  - Different role of endothelium/nitric oxide in 17beta-estradiol- and progesterone
      induced relaxation in rat arteries.
AB  - The present study was aimed to examine the different role of endothelium/nitric
      oxide in relaxation induced by two female sex hormones, 17beta-estradiol and
      progesterone in rat isolated aortas and mesenteric arteries. The isometric force
      of each ring was measured with Grass force-displacement transducers in the organ
      bathes. 17beta-Estradiol induced both endothelium-dependent and -independent
      relaxation in the rat aortas but only the endothelium-independent relaxation in
      the rat mesenteric arteries. In contrast. progesterone induced both endothelium
      dependent and -independent relaxation in the rat mesenteric arteries but only
      endothelium-independent relaxation in rat aortas. N(G)-Nitro-L-arginine methyl
      ester and methylene blue attenuated the relaxant response to 17beta-estradiol in
      the aortic rings or to progesterone in the mesenteric arteries. Pretreatment with
      L-arginine antagonized the effect of N(G)-nitro-L-arginine methyl ester on sex
      hormone-induced relaxation. The endothelium contribution to relaxation seems to
      only relate to lower concentrations of 17beta-estradiol and progesterone. In
      summary, the present results clearly demonstrate a different role of the
      functional endothelium in the relaxant response to 17beta-estradiol or
      progesterone in the conduit vessel (aorta) and the resistance vessels (mesenteric
      artery). Nitric oxide contributes largely to the endothelium-dependent relaxation
      induced by 17beta-estradiol in the isolated aortas or by progesterone in the
      mesenteric arteries.

PMID- 11589502
TI  - Antiangiogenic potential of 10-hydroxycamptothecin.
AB  - To investigate the antiangiogenic potential of 10-hydroxycamptothecin (HCPT), the
      proliferation of human microvascular endothelial cells (HMEC) and seven human
      tumor cell lines were detected by SRB assay, and the endothelial cell migration
      and tube formation were assessed using two in vitro model systems. Also,
      inhibition of angiogenesis was determined with a modification of the chick embryo
      chorioallantoic membrane (CAM) assay in vivo. Morphological assessment of
      apoptosis was performed by fluorescence microscope. HCPT 0.313-5 micromol x L(-1)
      treatment resulted in a dose-dependent inhibition of proliferation, migration and
      tube formation in HMEC cells, and HCPT 6.25-25 nmol x egg(-1) inhibited
      angiogenesis in CAM assay. HCPT 1.25-5 micromol x L(-1) elicited typical
      morphological changes of apoptosis including condensed chromatin, nuclear
      fragmentation, and reduction in volume in HMEC cells. HCPT significantly
      inhibited angiogenesis both in vitro and in vivo at relatively low
      concentrations, and this effect was related with induction of apoptosis in HMEC
      cells. These results taken collectively suggest that HCPT may be a potent
      antiangiogenetic and cytotoxic drug and further investigation is warranted.

PMID- 11589503
TI  - Decreased acetylcholine content and choline acetyltransferase mRNA expression in
      circulating mononuclear leukocytes and lymphoid organs of the spontaneously
      hypertensive rat.
AB  - It has been confirmed that the neurotransmitter acetylcholine (ACh) is present in
      blood; it is synthesized in T-lymphocytes by choline acetyltransferase (ChAT) and
      released upon T-lymphocyte activation. Both muscarinic and nicotinic ACh
      receptors have been identified on lymphocytes isolated from thymus, lymph node,
      spleen and blood, and their stimulation by muscarinic and nicotinic agonists
      elicits a variety of functional and biochemical effects, providing a strong
      argument that ACh synthesized and released from T-lymphocytes acts as an
      autocrine and/or paracrine factor regulating immune function. In the present
      study, we compared ACh levels in the blood, circulating mononuclear leukocytes
      (MNLs), thymus and spleen of spontaneously hypertensive rats (SHRs), which
      exhibit immune deficiencies related to the emergence of natural thymocytotoxic
      autoantibody, age-related decline of T-cell function and morphological changes in
      immune organs, with ACh levels in age-matched, normotensive Wistar Kyoto rats. In
      each case, ACh levels in 5-, 10- and 20-week-old SHRs were significantly lower
      than in WKYs. ChAT mRNA expression in MNLs was also significantly depressed in
      the SHRs. These results suggest that diminished synthesis and release of ACh from
      MNLs into blood and lymphoid organs likely reflects an immune deficiency related
      to T-cell dysfunction.

PMID- 11589504
TI  - Increased apoptosis in a variety of tissues of zinc-deficient rats.
AB  - Zinc deficient rats were prepared to investigate histopathological changes in
      thymus, testis, skin, esophagus, kidney and liver and the relationship between
      these changes and apoptosis. Seven-week-old male SD rats were given a Zn
      deficient diet (0% Zn diet) or a standard diet (0.02% Zn diet). The above
      mentioned organs were excised 1, 2, 3, 4, 5, 10, 13, and 34 weeks after
      initiating diet administration. Then, these organs were examined morphologically,
      and apoptotic changes were analyzed by either the TdT- mediated dUTP - biotin
      nick end labeling (TUNEL) or electrophoresis. Significant morphological changes
      were seen only in rats on the 0% Zn diet. After 4 weeks, atrophy of the thymus
      was seen. After 5 weeks, oligospemia was observed, and after 10 weeks, testicular
      atrophy accompanied by the loss of sperm cells and spermatocytes was confirmed.
      In addition, after 10 weeks, thickening of epithelia was seen in the skin and
      esophagus of rats on the 0% diet. During the observation period, no marked
      morphological changes were observed in the liver or kidney. In the thymus and
      testis of rats on the 0% Zn diet, prior to detecting any morphological changes,
      increases in apoptosis were confirmed at 1 and 3 weeks after initiating diet
      administration, respectively. In the kidney and liver, TUNEL positive cells
      appeared after 13 and 34 weeks, respectively. These observations suggest that the
      functional and morphological changes in the thymus and testis of rats on the 0%
      Zn diet are caused by increased apoptosis, and that even when the supply of Zn is
      terminated for only a short period of time, immunocytes and germ cells can not
      survive or regenerate sufficiently. Again, the fact that even in the liver and
      kidney, apoptosis was observed when administration of the 0% Zn diet was
      prolonged suggests that the appearance of apoptosis is dependent on the amount of
      Zn in tissues. In addition, the fact that increases in apoptosis were confirmed
      in the skin of rats on the 0% Zn diet, but not in the esophagus of these rats
      suggests that apoptosis does not directly cause thickening of stratified squamous
      epithelium in Zn deficient rats.

PMID- 11589505
TI  - Estrogen prevents destabilization of endothelial nitric oxide synthase mRNA
      induced by tumor necrosis factor alpha through estrogen receptor mediated system.
AB  - 17beta-estradiol up-regulates endothelial nitric oxide synthase (eNOS) expression
      in cultured endothelial cells. To clarify the role of mRNA stabilization in
      upregulation of eNOS expression, endothelial cells were incubated with
      actinomycin D as transcriptional inhibitor. Up to 10 hours incubation with 17beta
      estradiol alone did not affect significantly the stability of eNOS mRNA. As tumor
      necrosis factor-alpha (TNF-alpha) is associated with the progression of
      atherosclerosis, we examined the effect of 17beta-estradiol on eNOS mRNA
      destabilization with TNF-alpha. After 10 hours co-incubation with TNF-alpha,
      relative intensity of eNOS mRNA decreased to 50% of the intensity at the start
      time of incubation, however, it remained significantly 1.6 times in the presence
      of 17beta-estradiol. This inhibitory effect of 17beta-estradiol was abolished by
      the treatment of estrogen receptor antagonist, ICI 182,780. This is the first
      finding that 17beta-estradiol stabilizes eNOS mRNA destabilized by TNF-alpha
      through estrogen receptor mediated mechanism.

PMID- 11589506
TI  - Inhibitory effect of tetrabutylammonium ions on endothelium/nitric oxide-mediated
      vasorelaxation.
AB  - Apart from the well-described K+ channel blocking effects in vascular smooth
      muscle cells, monovalent quaternary ammonium ions may also interact with
      endothelial cells in the endothelium-intact mammalian arteries. The present study
      was aimed to examine the effect of tetrabutylammonium ions on endothelium
      dependent and -independent relaxation in the rat isolated aortic rings.
      Pretreatment with tetrabutylammonium concentration dependently reduced the
      endothelium-dependent relaxation induced by acetylcholine, cyclopiazonic acid and
      ionomycin. Tetrabutylammonium also inhibited endothelium-independent relaxation
      induced by hydroxylamine or nitroprusside. Pretreatment of endothelium-denuded
      rings with tetrabutylammonium did not affect relaxation induced by NS1619 or by
      diltiazem. In contrast, tetrabutylammonium significantly reduced the pinacidil-
      or cromakalim-induced relaxation. Tetrabutylammonium also inhibited the
      acetylcholine- but not nitroprusside-induced increase of tissue content of cyclic
      GMP in the aortic rings. The present study indicates that tetrabutylammonium ions
      could inhibit endothelial and exogenous nitric oxide-mediated aortic relaxation
      while it had no effect on relaxation induced by activation of Ca2+-activated K+
      channels (by NS1619) or by inhibition of voltage-gated Ca2+ channels (by
      diltiazem). The inhibitory effect on pinacidil- and cromakalim-induced relaxation
      suggests that tetrabutylammonium ions also inhibit ATP-sensitive K+ channels in
      aortic smooth muscle cells.

PMID- 11589507
TI  - Additive effects of intra-accumbens infusion of the cAMP-specific
      phosphodiesterase inhibitor, rolipram and cocaine on brain stimulation reward.
AB  - Evidence from cocaine self-administration studies suggests that increasing the
      activity of cyclic AMP (cAMP) pathways within the nucleus accumbens may produce a
      reduction in cocaine's reinforcing effects. Rolipram may increase intra-cellular
      levels of cAMP by selectively inhibiting Type IV phosphodiesterases, enzymes that
      catalyze cAMP breakdown. The present study was undertaken to test the hypothesis
      that infusion of rolipram into the nucleus accumbens would decrease cocaine
      induced enhancement of the sensitivity of brain stimulation reward (BSR)
      pathways. BSR thresholds were determined in rats after the systemic
      administration of cocaine (4 mg/kg IP) and the infusion of rolipram (0.2
      microg/side) into the nucleus accumbens both alone and in combination. Thresholds
      also were determined after the systemic administration of rolipram alone and, as
      a positive control, for amphetamine (10 microg/side) infused into the nucleus
      accumbens. BSR thresholds were significantly lowered below baseline levels
      following d-amphetamine administration suggesting that cannulae were in place to
      allow perfusion of reward pathways. Compared to values for saline alone,
      thresholds were lower after the injection of cocaine (4 mg/kg IP) or the infusion
      of rolipram (0.2 microg/side) into the nucleus accumbens. Treatment with the
      combination of cocaine and intra-nucleus accumbens rolipram produced a greater
      lowering of the BSR threshold than did administration of either rolipram or
      cocaine alone. Systemic administration of rolipram (0.5 mg/kg IP) either blocked
      the effects of BSR or raised BSR thresholds and produced stimulation-induced head
      jerking in most of the test animals. These results suggest that infusion into the
      nucleus accumbens of rolipram, an agent that putatively elevates cAMP levels in
      this structure, can enhance the sensitivity of reward pathways to BSR and can
      augment cocaine's actions on these pathways.

PMID- 11589508
TI  - Saturable transport of the neurokinin-1 non-peptide antagonist LY303870 across
      the rat blood-brain barrier after intravenous administration.
AB  - LY303870 (LY) is a non-peptide neurokinin-1 receptor antagonist that has effects
      on the brain after peripheral administration. We determined whether LY given by
      intravenous (iv) injection can cross the blood-brain barrier (BBB). Multiple-time
      regression analysis showed the unidirectional influx rate (Ki) from blood to
      brain for LY labeled with tritium to be 6.41+/-0.85 microl/g-min and influx was
      inhibited by unlabeled LY. HPLC and mass spectrometry showed LY was stable in
      blood and brain. LY reached a brain/serum ratio of 190+/-12 microl/g with about
      0.07% of the injected dose entering each gram of brain. These results show that
      LY is transported across the BBB from serum into brain by a saturable system.

PMID- 11589509
TI  - Effects of AH-9700, (+)-pentazocine, DTG and oxybutynin on micturition in
      anesthetized rats with acetone-induced cystitis.
AB  - We investigated the effects of AH-9700 (1-[2-(3,4-dihydro-6,7-dimethyl-2
      naphthalenyl)ethyl] pyrrolidine fumarate; a novel sigma receptor ligand), (+)
      pentazocine and 1,3-di-o-tolylguanidine (DTG) (two typical sigma receptor
      ligands), and oxybutynin (a currently used anti-pollakiuria drug) on
      cystometrograms in anesthetized rats with 30% acetone-induced cystitis. Compared
      to sham-treated rats, acetone-treated cystitis models exhibited an increase in
      urinary frequency during continuous filling cystometry. Intravenous
      administration of AH-9700 (1-5 mg/kg), (+)-pentazocine or DTG to the rats with
      cystitis dose-dependently prolonged micturition intervals and increased the
      micturition threshold pressure. Oxybutynin (1 mg/kg. i.v.) also extended
      micturition intervals, but decreased the micturition pressure. These results
      indicate that AH-9700, (+)-pentazocine and DTG improve abnormal frequent
      urination caused by acetone-induced cystitis in a manner different from that of
      oxybutynin.

PMID- 11589510
TI  - Mechanisms of the renal vasodilation caused by insulin in anesthetized pigs.
AB  - The present study was planned to determine the mechanisms involved in the renal
      vasodilation caused by insulin. Changes in flow caused by the intravenous
      infusion of 0.004 IU/kg/min of insulin at constant heart rate, aortic blood
      pressure, left ventricular contractility and blood levels of glucose and
      potassium in the left renal artery were assessed using an electromagnetic
      flowmeter. In ten pigs, infusion of insulin caused an increase in renal blood
      flow which averaged 12.8% of the control values. After hemodynamic variables had
      returned to control values, insulin infusion was repeated in five pigs following
      blockade of alpha-adrenergic receptors with injection of phentolamine into the
      renal artery and in the other five pigs following blockade of nitric oxide
      formation with injection in the same artery of Nomega-nitro-L-arginine methyl
      ester (L-NAME). After blockade of alpha-adrenergic receptors, insulin infusion
      caused an increase in renal blood flow which averaged 18.1% of the control
      values, being significantly enhanced with respect to the increase previously
      obtained in the same pigs. On the contrary, after blockade of nitric oxide
      formation insulin infusion caused a decrease in renal blood flow which averaged
      6.5% of the control values. These responses were respectively abolished by the
      subsequent injection into the renal artery of L-NAME and phentolamine. The
      present study showed that the renal vasodilation caused by insulin in the
      anesthetized pig was the result of two opposite effects which involved a
      predominant vasodilation mediated by the release of nitric oxide from the
      endothelium and a sympathetic vasoconstrictor mechanism mediated by alpha
      adrenergic receptors.

PMID- 11589511
TI  - Salt intake and intestinal dopaminergic activity in adult and old Fischer 344
      rats.
AB  - We have earlier shown that the renal dopaminergic system failed to respond to
      high salt (HS) intake in old (24-month-old) Fisher 344 rats (Hypertension
      1999;34:666-672). In the present study, intestinal Na+,K+-ATPase activity and
      intestinal dopaminergic tonus were evaluated in adult and old Fischer 344 rats
      during normal salt (NS) and HS intake. Basal intestinal Na+,K+-ATPase activity
      (nmol Pi/mg protein/min) in adult rats (142+/-6) was higher than in old Fischer
      344 rats (105+/-7). HS intake reduced intestinal Na+,K+-ATPase activity by 20%
      (P<0.05) in adult, but not in old rats. Dopamine (1 microM) failed to inhibit
      intestinal Na+,K+-ATPase activity in both adult and old Fischer 344 rats (NS and
      HS diets). In adult animals, co-incubation of pertussis toxin with dopamine (1
      microM) produced a significant inhibitory effect in the intestinal Na+,K+-ATPase
      activity. L-DOPA and dopamine tissue levels in the intestinal mucosa of adult
      rats were higher (45+/-9 and 38+/-4 pmol/g) than those in old rats (27+/-9 and
      14+/-1 pmol/g). HS diet did not change L-DOPA and DA levels in both adult and old
      rats. DA/L-DOPA tissue ratios, an indirect measure of dopamine synthesis, were
      higher in old (1.1+/-0.2) than in adult rats (0.6+/-0.1). Aromatic L-amino acid
      decarboxylase (AADC) activity in the intestinal mucosa of old rats was higher
      than in adult rats. HS diet increased the AADC activity in adult rats, but not in
      old rats. It is concluded that intestinal dopaminergic tonus in old Fisher 344
      rats is higher than in adult rats and is accompanied by lower basal intestinal
      Na+,K+-ATPase activity. In old rats, HS diet failed to alter the intestinal
      dopaminergic tonus or Na+,K+-ATPase activity, whereas in adult rats increases in
      AADC activity were accompanied by decreases in Na+,K+-ATPase activity. The
      association between salt intake, increased dopamine formation and inhibition of
      Na+,K+-ATPase at the intestinal level was not as straightforward as that
      described in renal tissues.

PMID- 11589512
TI  - Comparative study on sodium transport and Na+,K+-ATPase activity in Caco-2 and
      rat jejunal epithelial cells: effects of dopamine.
AB  - The present study reports on the effects of dopamine on sodium transepithelial
      transport and Na+,K+-ATPase activity in Caco-2 cells, a human epithelial
      intestinal cell line which undergoes enterocyte differentiation in culture, and
      jejunal epithelial cells from 20 day old Wistar rats. Addition of amphotericin B
      to the mucosal side stimulated Isc in a concentration dependent manner (Caco-2
      cells, EC50=0.9 [0.5, 1.7] microM; rat jejunum, EC50=7.4 [0.8; 70.1] microM). The
      presence of 1 microM dopamine did not change the effect of amphotericin B in Caco
      2 cells, but produced a significant (P<0.05) decrease in the maximal effect of
      amphotericin B in the rat jejunum. Dopamine (1 microM), added to the serosal
      side, did not change the Isc profile in Caco-2 cells, but produced a significant
      increase in the rat jejunum. This effect was antagonized by SKF 83566 (1 microM),
      but not S-sulpiride (1 microM), and was mimicked by SKF 38393 (10 nM), but not by
      quinerolane (10 nM). Basal Na+,K+-ATPase activity (in nmol Pi mg protein(-1) min(
      1)) in Caco-2 cells (49.5+/-0.2) was similar to that observed in isolated rat
      jejunal epithelial cells (52.3+/-3.4). Dopamine (1 microM) significantly (P<0.05)
      decreased Na+,K+-ATPase activity in rat jejunal epithelial cells, but failed to
      inhibit Na+,K+-ATPase in Caco-2 cells. This effect of dopamine was antagonized by
      SKF 83566 (1 microM), but not S-sulpiride (1 microM), and was mimicked by SKF
      38393 (10 nM), but not by quinerolane (10 nM). The specific binding of [3H]-Sch
      23390 to the rat intestinal mucosa was saturable with an apparent dissociation
      constant (KD) of 2.4 (0.4; 4.5) nM and maximum receptor density of 259.8+/-32.6
      fmol/mg protein. No significant specific binding of [3H]-Sch 23390 was observed
      in membranes from Caco-2 cells. In conclusion, the results obtained show that D1
      like receptor mediated effects of dopamine in the rat jejunum on sodium
      absorption are absent in Caco-2 cells, most probably because this cell line does
      not express D1-like dopamine receptors, which ultimately are responsible for the
      inhibitory effect of the amine upon intestinal Na+,K+-ATPase.

PMID- 11589513
TI  - A potent AMPA/kainate receptor antagonist, YM90K, attenuates the loss of N
      acetylaspartate in the hippocampal CA1 area after transient unilateral forebrain
      ischemia in gerbils.
AB  - By analyzing histological damages and the regional N-acetylaspartate (NAA) level
      simultaneously, we evaluated the effect of an alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist, YM90K [6-(1H
      imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione monohydrochloride], in
      unilateral forebrain ischemia in gerbils. The right common carotid artery was
      clipped for 5 min under ether anesthesia, and reperfused for 7 days. The frozen
      brain sections were lyophilized and the hippocampal CA1 area was dissected out
      for HPLC assay of NAA. An adjacent section was stained with hematoxylin-eosin for
      counting survived neurons per 1 mm pyramidal layer of the hippocampal CA1 area.
      Postischemic administration of YM90K at 20 mg/kg and 25 mg/kg attenuated the
      decrease of both the number of survived neurons and the NAA level on the ischemic
      side in a dose-dependent manner. A significant linear correlation was observed
      between the NAA level and the number of intact neurons. These results indicated
      that the NAA level could be used as an index of neuroprotective effects of
      pharmacological agents in global cerebral ischemia.

PMID- 11589514
TI  - Corticotropin releasing hormone stimulates proliferation of keratinocytes.
AB  - Corticotropin releasing hormone (CRH) is a potent mediator of stress responses
      and stress-induced disorders. Consistent with the broad range of roles proposed
      for CRH, high-affinity binding sites have been found in various peripheral sites.
      Recently two types of CRH specific receptor have been identified. Expression of
      CRH receptor 1 (CRH-R1) gene has been detected in human keratinocyte, but the
      effects of CRH to keratinocytes are still unknown. We tested whether CRH induced
      keratinocyte proliferation via interaction with CRH R1. Expression of CRH-R1 mRNA
      in the human keratinocyte and HSC-2, keratinocyte cell line, was analyzed by RT
      PCR. The human keratinocyte and HSC-2 were recognized to have CRH-R1 expression
      ability. CRH signal is transduced into a cAMP-activated metabolic pathway via
      interaction with CRH-R1. Radioimmunoassay indicated that CRH binds to CRH
      receptor in HSC-2 cell when activating the metabolic pathway. Using thymidine
      incorporation assay, CRH had proliferative effect to HSC-2. This study suggests
      that CRH induces the proliferation of keratinocytes via interation with CRH
      receptors.

PMID- 11589515
TI  - Existence of both neuropeptide Y, Y1 and Y2 receptors in pig spleen: evidence
      using subtype-selective antagonists in vivo.
AB  - The effects of the first selective, non-peptide, NPY Y2 receptor antagonist (S)
      N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]
      2-oxoethyl]cyclopentyl]acetyl]-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H
      1,2,4-triazol-4-yl]ethyl]-argininamid (BIIE0246) were studied on splenic vascular
      responses evoked in the pig in vivo. BIIE0246 abolished the splenic
      vasoconstrictor response to the NPY Y2 receptor agonist N
      acetyl[Leu25Leu31]NPY(24-36), but did not affect the response to the NPY Y1
      receptor agonist [Leu31Pro34]NPY, which in turn was abolished by the selective
      NPY Y1 receptor antagonist (2R)-5-([amino(imino)methyl]amino)-2-[(2,2
      diphenylacetyl)amino]-N-[(IR)-1-(4-hydroxyphenyl)ethyl]-pentanamide (H 409/22).
      Furthermore, the PYY-evoked splenic vasoconstrictor response was partially
      antagonized by BIIE0246 and subsequently almost abolished by the addition of H
      409/22. It is concluded that BIIE0246 exerts selective (vs the NPY Y1 receptor)
      NPY Y2 receptor antagonism, and thus represents an interesting tool for
      classification of NPY receptors, in vivo. In addition, evidence for NPY Y2
      receptor mediated vasoconstriction was presented. Furthermore, both NPY Y1 and Y2
      receptors are involved in the splenic vasoconstrictor response to PYY.

PMID- 11589516
TI  - Liposome-encapsulated superoxide dismutase suppresses liposome-mediated
      augmentation of TNF-alpha production from peripheral blood leucocytes.
AB  - Liposome-encapsulated hemoglobin (LEH), a candidate for a red cell substitute,
      has been reported to be cleared from circulation primarily by the phagocytic
      system and modulate the production of inflammatory cytokines, such as TNF-alpha
      and IL-6, both in vivo and in vitro. In this study, we investigated the effects
      of liposome vesicles on the LPS-induced TNF-alpha production using a whole blood
      culture system. We also studied the effects of superoxide dismutase (SOD)
      encapsulated in liposome on the cytokine production. The pre-treatment of whole
      blood with liposome vesicles potentiated the LPS-induced TNF-alpha production.
      The encapsulation of SOD in the liposome vesicles suppressed the liposome
      mediated augmentation of TNF-alpha production in a dose-dependent manner. These
      results suggest that encapsulation of SOD in LEH decreases the production of
      inflammatory cytokines from the phagocytic system which may be caused or
      augmented by LEH infusion in vivo.

PMID- 11589517
TI  - Synergism between cocaine and atropine at the caudal ventrolateral medulla of
      cats.
AB  - We have previously reported that the anticholinergic properties of cocaine may be
      important in cocaine induced apneusis. We have studied the effects of the
      cholinergic muscarinic antagonist atropine (ATR) on cocaine induced apneusis at
      the caudal chemosensitive areas of the ventrolateral medulla oblongata (CVLM).
      Experiments were performed in urethane anesthetized and tracheotomized cats with
      the CVLM surgically exposed. Topical application of ATR (44 mM ) to the CVLM
      produced significant decrements in minute ventilation (V(E)) and mean arterial
      blood pressure (MABP) (P<0.05) but the effects on tidal volume (V(T)),
      respiratory frequency (f) and heart rate (HR) were not significant.
      Administration of cocaine (37 mM) to ATR pretreated animals increased the
      incidence of cocaine induced respiratory arrest to more than twofold greater than
      when cocaine was administered in the absence of pretreatment. The ATR pretreated
      animals that did not experience inspiratory arrest after cocaine were shown to
      exhibit significant decrements in f and V(E) as a consequence of prolonged
      inspiratory pauses. The reduction in MABP after cocaine in ATR pretreated animals
      was also significant. These results suggest that ATR enhances the central
      respiratory toxicity of cocaine by acting synergistically at CVLM chemosensitive
      sites.

PMID- 11589518
TI  - Carbohydrate specificity of a toxic lectin, abrin A, from the seeds of Abrus
      precatorius (jequirity bean).
AB  - To elucidate of the mechanism of intoxication, the affinity of a toxic lectin,
      abrin A, from the seeds of Abrus precatorius for mammalian carbohydrate ligands,
      was studied by enzyme linked lectinosorbent assay and by inhibition of abrin A
      glycan interaction. From the results, it is concluded that: (1) abrin A reacted
      well with Gal beta1-->4GlcNAc (II), Gal alpha1-->4Gal (E), and Gal beta1-
      >3GalNAc (T) containing glycoproteins. But it reacted weakly with sialylated gps
      and human blood group A,B,H active glycoproteins (gps); (2) the combining site of
      abrin A lectin should be of a shallow groove type as this lectin is able to
      recognize from monosaccharides with specific configuration at C-3, C-4, and deoxy
      C-6 of the (D)Fuc pyranose ring to penta-saccharides and probably internal Gal
      alpha,beta-->; and (3) its binding affinity toward mammalian structural features
      can be ranked in decreasing order as follows: cluster forms of II, T, B/E (Gal
      alpha1-->3/4Gal) > monomeric T > monomeric II > monomeric B/E, Gal > GalNAc >
      monomeric I >> Man and Glc (inactive). These active glycotopes can be used to
      explain the possible structural requirements for abrin A toxin attachment.

PMID- 11589519
TI  - Carbohydrate specificity of a lectin isolated from the fungus Sclerotium rolfsii.
AB  - In order to investigate the functional roles of a phytopathogenic fungal lectin
      (SRL) isolated from the bodies of Sclerotium rolfsii, the binding properties of
      SRL were studied by enzyme linked lectinosorbent assay and by inhibition of SRL
      glycan interaction. Among glycoproteins (gp) tested for binding, SRL reacted
      strongly with GalNAc alpha1-->4Ser/Thr (Tn) and/or Gal beta1-->3GalNAc alpha1-
      >(T(alpha)) containing gps: human T(alpha) and Tn glycophorin, asialo salivary
      gps, and asialofetuin, but its reactivity toward sialylated glycoproteins was
      reduced significantly. Of the sugar ligands tested for inhibition of SRL
      asialofetuin binding, Thomsen-Friedenreich residue (T(alpha)) was the best, being
      22.4 and 2.24 x 10(3) more active than GalNAc and Gal beta1--> residues,
      respectively. Other ligands tested were inactive. When the glycans used as
      inhibitors, T(alpha), and/or Tn containing gps, especially asialo PSM, asialo
      BSM, asialo OSM, active antifreeze gp, asialo glycophorin and Tn-glycophorin were
      very active, and 1.0 x 10(4) times more potent than GalNAc. From these results,
      it is clear that the combining site of SRL should be of a cavity type and
      recognizes only Tn and T(alpha) residues of glycans; it is suggested that
      T(alpha) and Tn glycotopes, which are present only in abnormal carbohydrate
      sequences of higher orders of mammal, are the most likely sites for
      phytopathogenic fungal attachment as an initial step of infection. The affinity
      of SRL for ligands can be ranked in decreasing order as follows: multivalent
      T(alpha) and Tn >> monomeric T(alpha) and Tn > GalNAc >>> II (Gal beta1-
      >4GlcNAc), L (Gal beta1-->4Glc), and Gal.

PMID- 11589520
TI  - Tissue uptake of ketamine and norketamine enantiomers in the rat: indirect
      evidence for extrahepatic metabolic inversion.
AB  - Ketamine, used clinically as an intravenous analgetic and dissociative
      anaesthetic agent, is a racemate with both pharmacokinetic and pharmacodynamic
      enantioselectivity. S-ketamine has been found have a higher clearance and greater
      potency than R-ketamine as well as a greater therapeutic index. We performed a
      study in rats with two complementary paradigms: (i) constant rate "washin"
      infusion until fatal, (ii) brief infusion then "washout". These, respectively,
      allowed examination of ketamine and norketamine serial plasma enantiomer
      concentrations and tissue distribution at maximal and minimal drug effects. Both
      paradigms found plasma concentrations of R-ketamine>S-ketamine; however, tissue
      distribution coefficients for S-ketamine>R-ketamine. For paradigm (i), plasma
      concentrations of R-norketamine>S-norketamine; for paradigm (ii), R
      norketamine>>S-norketamine initially, but S-norketamine>>R-norketamine later.
      Comparison of distribution coefficients of ketamine and norketamine enantiomers
      for the two paradigms provided indirect evidence for metabolic inversion. During
      washin, when circulating concentrations of ketamine enantiomers were high, uptake
      and metabolism occurred predominantly in the kidney and to a lesser extent in
      liver, lung and gut, with formation of R-norketamine by a (presumed) first-order
      process predominating. However, following washout, when circulating
      concentrations of ketamine enantiomers were low, uptake and metabolism was
      dominated by the kidney and gut. Under these conditions inversion of R- to S
      ketamine appeared to predominate with subsequent metabolism to S-norketamine by
      (presumed) zero-order processes. In summary, different profiles for the uptake
      and metabolism of ketamine enantiomers were apparent following constant rate
      washin, and brief infusion washout, paradigms with i.v. rac-ketamine. Uptake into
      most tissues, and metabolism in some tissues, was enantioselective.

PMID- 11589521
TI  - The role of nitric oxide in ischaemia/reperfusion injury of isolated hearts from
      severely atherosclerotic mice.
AB  - Nitric oxide (NO) may play an essential role for maintenance of cardiac function
      and perfusion, while endothelial dysfunction of atherosclerotic vessels may
      aggravate ischaemia/reperfusion injury. This paper investigates the role of
      nitric oxide in ischaemia/reperfusion injury in hearts with coronary
      atherosclerosis. Hearts of apolipoprotein E/LDL receptor double knockout
      (ApoE/LDLr KO) mice fed an atherogenic diet for 7-9 months were isolated and
      Langendorff-perfused with 40 minutes of global ischaemia and 60 minutes
      reperfusion, and funtion and infarction compared with hearts of C57BL/6 controls
      in the prescence or abscence of the NO-donor SNAP or the NOS inhibitor L-NAME.
      Hearts of animals with atherosclerosis were more susceptible to
      ischaemia/reperfusion injury than hearts of animals with healthy vessels, evident
      as more impaired left ventricular performance. SNAP protected function and
      reduced infarct size in atherosclerotic hearts, but the same concentration of
      SNAP was detrimental in normal hearts, perhaps due to NO-overproduction and
      peroxynitrite formation demonstrated immunohistochemically as increased formation
      of nitrosylated tyrosine. A low concentration of SNAP protected against
      ischaemia/reperfusion dysfunction in normal hearts. L-NAME decreased left
      ventricular performance in atherosclerotic hearts. These findings suggest that
      impaired endothelium dependent function contributes to reperfusion injury in
      coronary atherosclerosis.

PMID- 11589522
TI  - Impact of media.

PMID- 11589523
TI  - Borderline pathology.

PMID- 11589524
TI  - Migraine and sertraline.

PMID- 11589525
TI  - Citalopram in social phobia.

PMID- 11589526
TI  - Ten-year research review of physical injuries.
AB  - OBJECTIVE: To review the past 10 years of research relevant to psychiatry on
      injuries in children and adolescents. METHOD: A literature search of databases
      for "wounds and injuries, excluding head injuries," was done with Medline and
      PsycINFO, yielding 589 and 299 citations, respectively. Further searching
      identified additional studies. RESULTS: Progress is occurring in prevention, pain
      management, acute care, psychiatric treatment, and outcomes. The emotional and
      behavioral effects of injuries contribute to morbidity and mortality. Psychiatric
      assessment, crisis intervention, psychotherapy, psychopharmacological treatment,
      and interventions for families are now priorities. Research offers new
      interventions for pain, delirium, posttraumatic stress disorder, depression,
      prior maltreatment, substance abuse, disruptive behavior, and end-of-life care.
      High-risk subgroups are infants, adolescents, maltreated children, suicide
      attempters, and substance abusers. Staff training improves quality of care and
      reduces staff stress. CONCLUSIONS: Despite the high priority that injuries
      receive in pediatric research and treatment, psychiatric aspects are neglected.
      There is a need for assessment and for planning of psychotherapeutic,
      psychopharmacological, and multimodal treatments, based on severity of injury,
      comorbid psychopathology, bodily location(s), and prognosis. Psychiatric
      collaboration with emergency, trauma, and rehabilitation teams enhances medical
      care. Research should focus on alleviating pain, early psychiatric case
      identification, and treatment of children, adolescents, and their families, to
      prevent further injuries and reduce disability.

PMID- 11589527
TI  - Enuresis and encopresis: ten years of progress.
AB  - OBJECTIVE: To review the progress made over the past decade with regard to the
      treatment of enuresis and encopresis, as well as advances in the understanding of
      etiological mechanisms. METHOD: Separate computerized literature (English
      language only) searches of Medline and PsycINFO databases were conducted under
      the parameter of enuresis and children-adolescents, as well as encopresis and
      children-adolescents. RESULTS: There has been a substantial decrease in published
      research concerning the use of imipramine to treat enuresis compared with the
      prior two decades, accompanied by a corresponding increase in the number of
      papers concerning desmopressin acetate (DDAVP), which has become the primary
      pharmacological treatment. Genetic studies of large pedigrees have further
      confirmed the importance of heritable factors. With regard to encopresis, the
      research has focused primarily on pathophysiological factors related to the colon
      and anal sphincter. CONCLUSIONS: The widespread use of DDAVP has been the primary
      addition to treatment strategies over the past decade. The bell-and-pad method of
      conditioning, the only major treatment that has enduring benefit after being
      withdrawn, is the most cost-effective and appears to be underutilized. Research
      into etiological mechanisms has focused primarily on the mechanism of action of
      DDAVP and advances in the understanding of genetic factors. Advances in the
      treatment and etiological understanding of encopresis have been less impressive.

PMID- 11589528
TI  - Association between psychiatric disorders and the progression of tobacco use
      behaviors.
AB  - OBJECTIVE: To examine the progression of tobacco use and the patterns of
      comorbidity of tobacco use and psychiatric disorders. METHOD: The authors
      conducted analyses of prospective and retrospective reports, collected from 1988
      to 1998, of a sample of high- and low-risk youths identified on the basis of the
      presence or absence of a parental history of substance abuse or dependence.
      RESULTS: A parental history of substance use disorders was associated with
      regular tobacco use and nicotine dependence, but not with experimentation for all
      youths. Individual and composite psychiatric diagnoses were strongly associated
      with nicotine dependence, but not with regular use or experimentation. While the
      presence of an affective disorder and drug abuse/dependence generally increased
      the risk for co-occurring nicotine dependence, analyses based on the temporal
      onset of disorders showed that it was the initiation of alcohol or drug use that
      predicted the progression to nicotine dependence. For low-risk youths,
      oppositional defiant disorder was the single psychiatric risk factor that
      predicted the transition to nicotine dependence. CONCLUSIONS: This study adds to
      the accumulating evidence that has implicated comorbid psychiatric disorders in
      the etiology and subsequent course of nicotine dependence. In addition, family
      history may represent an important indicator of an increased risk for nicotine
      dependence.

PMID- 11589529
TI  - Sequences of substance use among American Indian adolescents.
AB  - OBJECTIVE: To determine whether the predominant pattern of the sequence of use of
      different classes of substances among a large sample of American Indian (AI)
      adolescents is consistent with Stage Theory [i.e., (1) alcohol, (2) marijuana,
      (3) other illicit drugs, and (4) cocaine]. METHOD: Data came from surveys
      completed by 1,562 AI high school students in 1993. Pairwise comparisons of age
      of first use for alcohol, marijuana, inhalants, cocaine, and other illicit drugs
      were examined, as were the prevalence rates of specific sequences of substance
      use. RESULTS: Thirty-five percent of the AI youths who had used both alcohol and
      marijuana reported using alcohol first. Seventy-five percent of youths who had
      used three or more substances reported a sequence of first use that was
      inconsistent with Stage Theory. However, a general pattern of using alcohol,
      marijuana, and/or inhalants prior to the use of cocaine and other illicit drugs
      was observed. Sequences of first use varied by gender, age of first substance
      use, community, and number of classes of substances used. CONCLUSIONS: To enhance
      the validity of Stage Theory for AI adolescents, the authors recommend its
      revision to include alcohol, marijuana, and inhalants as initiating substances.

PMID- 11589530
TI  - Long-term sertraline treatment of children and adolescents with obsessive
      compulsive disorder.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of sertraline in the long
      term treatment of pediatric obsessive-compulsive disorder (OCD). METHOD: Children
      (6-12 years; n= 72) and adolescents (13-18 years; n = 65) with DSM-III-R-defined
      OCD who had completed a 12-week, double-blind, placebo-controlled sertraline
      study were given open-label sertraline 50 to 200 mg/day in this 52-week extension
      study. Concomitant psychotherapy was allowed during the extension study Outcome
      was evaluated by the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS),
      National Institute of Mental Health Global Obsessive-Compulsive Scale, and
      Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scores.
      RESULTS: Significant improvement (p < .0001) was demonstrated on all four outcome
      parameters on an intent-to-treat analysis for the overall study population (n =
      132), as well as the child and the adolescent samples. At endpoint, 72% of
      children and 61% of adolescents met response criteria (>25% decrease in CY-BOCS
      and a CGI-I score of 1 or 2). Significant (p < .05) improvements were also
      demonstrated from the extension study baseline to endpoint on all outcome
      parameters in those patients who received sertraline during the 12-week, double
      blind acute study. Long-term sertraline treatment was well tolerated, and there
      were no discontinuations due to changes in vital signs, laboratory values, or
      electrocardiograms. CONCLUSION: Sertraline (50-200 mg/day) was effective and
      generally well tolerated in the treatment of childhood and adolescent OCD for up
      to 52 weeks. Improvement was seen with continued treatment.

PMID- 11589531
TI  - Familial predictors of treatment outcome in childhood anxiety disorders.
AB  - OBJECTIVE: To determine whether family factors are predictive of outcome in
      children with anxiety disorders who are receiving cognitive-behavioral treatment.
      METHOD: Participants were 61 children aged 8 to 12 years (mean = 10.0, SD = 1.4)
      with Axis I anxiety disorders who had been referred to a large Toronto children's
      hospital. Parents and children completed measures assessing family functioning,
      parenting stress, parental frustration, and parental psychopathology before and
      after treatment. Outcome measures included clinician-rated functioning
      (Children's Global Assessment Scale) and self- and parent-rated anxiety (Revised
      Children's Manifest Anxiety Scale). RESULTS: Child ratings of family dysfunction
      and frustration predicted clinician-rated improvement (total R2 = 0.28, p <
      .001). Mother and father reports of family dysfunction, and maternal parenting
      stress, predicted mother-rated child improvement (total R2 = 0.18, p < .01).
      Father-rated somatization and child reports of family dysfunction and frustration
      predicted child-rated improvement (total R2 = 0.25, p < .001). Several family
      factors improved with treatment. CONCLUSION: Family dysfunction appears to be
      related to less favorable treatment outcome in children with anxiety disorders.

PMID- 11589532
TI  - Differentiating childhood-onset schizophrenia from psychotic mood disorders.
AB  - OBJECTIVE: The authors systematically examined a sample of patients who were
      referred to an ongoing National Institute of Mental Health (NIMH) study of
      childhood-onset schizophrenia (COS), but who received diagnoses of mood disorders
      at the NIMH, to analyze the reliability of these research-setting diagnoses and
      to characterize the patients clinically. Pilot data regarding the clinical course
      of these patients over a 2- to 7-year follow-up period were also obtained.
      METHOD: Thirty-three cases were selected from the 215 pediatric patients who had
      been screened in person from 1991 to 1999 for admission to the COS study. These
      33 patients had been excluded from the COS study on the basis of a day-long
      evaluation, including a structured diagnostic interview, which yielded a
      diagnosis of a mood disorder rather than schizophrenia. This subgroup, together
      with six COS subjects (for a total N= 39), were included in a diagnostic
      reliability study in which they were reevaluated by three psychiatrists who were
      blind to the initial research diagnosis. In addition, pilot follow-up data
      regarding current function and treatment status were obtained for 25 of the 33
      patients with mood disorders. RESULTS: Overall, the interrater reliability of the
      three raters was excellent (kappa = 0.90). Global reliability between these
      raters and the NIMH research diagnoses was good (average kappa across diagnoses =
      0.61), and agreement for those patients who had mood disorders was good (86%
      agreement; kappa = 0.60). Pilot follow-up data indicate that none of the subjects
      with a diagnosed mood disorder developed a clinical course resembling
      schizophrenia. CONCLUSIONS: Many of the patients referred to the NIMH COS study
      with clinical diagnoses of schizophrenia had psychotic mood disorders diagnosed
      on the basis of a comprehensive research evaluation including structured
      diagnostic interviews, and these research diagnoses were reliable. The diagnosis
      of COS is difficult and requires a time-consuming evaluation process.

PMID- 11589533
TI  - Suicide attempts in the "comprehensive community mental health services for
      children and their families" program.
AB  - OBJECTIVE: To compare clinical characteristics of youths who had attempted
      suicide recently, previously but not recently, repeatedly, or never. METHOD: The
      sample comprised 4,677 youths receiving services between 1993 to 1998 in 22
      communities and participating in the national evaluation of the Comprehensive
      Community Mental Health Services for Children and Their Families Program. Data on
      suicide attempts, demographics, and clinical characteristics were obtained from
      intake interviews and referring agencies. Chi-square and univariate analyses of
      variance were used for between-group comparisons. RESULTS: Twenty-one percent of
      the sample had a history of attempted suicide. Previous and repeat attempters
      were more likely to have a history of family violence and substance abuse. Repeat
      attempters were most likely to have depression, while never and previous (but not
      recent) attempters were more likely to have conduct disorder. Other clinical
      differences were also found. CONCLUSIONS: Among children receiving mental health
      services, those who attempt suicide experience more and different types of
      distress, depending on the recency and frequency of attempts. Clinicians should
      be aware that depression is not a necessary factor in predicting suicide attempts
      and that suicide risk is also associated with violent and aggressive behaviors.

PMID- 11589534
TI  - Open trial of risperidone in 24 young children with pervasive developmental
      disorders.
AB  - OBJECTIVE: To describe tolerability and efficacy of risperidone in very young
      children with pervasive developmental disorders. METHOD: Twenty-four children
      aged 3.6 to 6.6 years (mean 4.6 years +/- 8 months) enrolled during 1999 and 2000
      participated in a 16-week open-label trial with risperidone monotherapy. Outcome
      measures included the Children's Psychiatric Rating Scale (CPRS), Childhood
      Autism Rating Scale (CARS), Clinical Global Impression-Improvement (CGI-I), and
      Children's Global Assessment Scale (C-GAS). RESULTS: Two subjects did not
      complete the trial because of side effects. The optimal dose was 0.5 mg/day.
      After the treatment a 21% improvement in CPRS and a 14% improvement in CARS total
      scores was found. Items related to behavioral control (hyperactivity,
      fidgetiness, rhythmic motions) and affect regulation (lability of affect, angry
      affect) improved more than 25%. Based on improvement of at least 25% on the CPRS
      and a score of 1 or 2 on the CGI-I, eight subjects were considered responders.
      Functional impairment (C-GAS) improved more than 25%. Thirteen subjects (54%)
      were free of any side effects; in the other participants risperidone was well
      tolerated. Only three subjects had a weight gain greater than 10%. CONCLUSIONS:
      Low-dose risperidone may positively affect symptoms in young autistic children,
      improving disruptive/hyperactive behavior and affective dysregulation. Further
      controlled studies in this age group are warranted.

PMID- 11589535
TI  - Adolescent anorexia nervosa: the catch-up effect in bone mineral density after
      recovery.
AB  - OBJECTIVE: To determine whether bone mineral density (BMD) loss can be reversed
      in adolescent anorexic patients. METHOD: A prospective study with 108 anorexia
      nervosa patients (DSM-IV) from 12 to 17 years of age at the Eating Disorders Unit
      in the Hospital Clinic of Barcelona (Spain). They were first evaluated by dual
      energy x-ray absorptiometry in lumbar spine and femoral neck consecutively from
      1997 until 1999 and reexamined after 6 to 30 months. Results were compared with
      normative values of bone mass. RESULTS: Patients with poor outcome (n = 44) had a
      bone mass loss. Patients with good short-term outcome were divided in two groups.
      The group with normal BMD at first evaluation (n = 41) had a bone mass gain per
      year of 3.0% at lumbar spine and 0.5% at femoral neck. The group with low BMD at
      first evaluation (n = 23) had an increase per year of 9.1% at lumbar spine and
      4.5% at femoral neck. In a multiple linear regression analysis with the variables
      body mass index, age, months with menstruation, and BMD zscore at first
      evaluation, the only predictor of BMD increase was the first z score both at the
      lumbar spine (coefficient R = 0.64; p < .001) and at the femoral neck
      (coefficient R = 0.5; p < .001). CONCLUSIONS: There is a catch-up effect in
      adolescent patients with low BMD but good short-term outcome.

PMID- 11589536
TI  - Psychophysiological responses in ADHD boys with and without conduct disorder:
      implications for adult antisocial behavior.
AB  - OBJECTIVE: Several studies have demonstrated that the presence of attention
      deficit/hyperactivity disorder (ADHD) in childhood increases the risk of
      antisocial behavior developing in adulthood. However, because previous research
      did not consider comorbid conduct disorder (CD), the question of whether ADHD by
      itself or only the association of ADHD with CD implies a risk of adult antisocial
      behavior developing is still under discussion. METHOD: Because several
      characteristics of psychophysiological response had been shown to be associated
      with future increased likelihood of adult antisocial behavior, autonomic arousal
      as well as electrodermal responses to orienting and aversive stimuli were
      assessed in 26 boys with ADHD+CD compared with 21 boys with ADHD alone and 21
      controls. RESULTS: Boys with a comorbid condition of ADHD+CD showed a decrement
      of autonomic responses and a more rapid habituation to orienting and aversive
      startling stimuli compared with age-matched children with ADHD alone.
      CONCLUSIONS: Boys with ADHD+CD show a psychophysiological response pattern that
      is very similar to that reported in antisocial personalities. These findings give
      further support for a high persistence of antisocial behavior from childhood to
      adulthood, while no evidence was found that ADHD itself is associated with a
      predisposition to antisocial behavior.

PMID- 11589537
TI  - Ethical problems and principles in human research.

PMID- 11589538
TI  - Genetics of childhood disorders: XXXI. Autoimmune disorders, part 4: is Sydenham
      chorea an autoimmune disorder?

PMID- 11589539
TI  - The effect of partners' characteristics on teenage pregnancy and its resolution.
AB  - CONTEXT: Although the determinants of whether a teenage woman has a nonmarital
      pregnancy and how such a pregnancy is resolved have been widely investigated,
      little is known about the effect of her partner's characteristics or the joint
      influence of the two partners' characteristics on nonmarital teenage pregnancy.
      METHODS: Data from the 1995 National Survey of Family Growth are used to examine
      whether the characteristics of teenage women and their partners affect the
      likelihood of a nonmarital pregnancy and how the pregnancy is resolved. The data
      are corrected for underreporting of abortions. RESULTS: More than 17% of teenage
      women are estimated to have become pregnant during their first nonmarital teenage
      sexual relationship. About 44% of these pregnancies result in a nonmarital birth
      and about 18% in a marital birth, while 37% end in an abortion. The likelihood of
      nonmarital pregnancy declines as age at first intercourse rises, but age does not
      affect how such a pregnancy is resolved. Women who are older than their first
      partner are more likely to become pregnant than those who are the same age, and
      their pregnancies are less likely to end in abortion than in a marital birth.
      Women who are younger than their first partner are no more likely to become
      pregnant than other women after the effects of other characteristics are taken
      into account. The male partner's education is negatively associated with the
      likelihood of nonmarital pregnancy but is positively associated with the
      likelihood of abortion if a pregnancy occurs. Differences between partners in
      race or ethnicity do not affect the likelihood of a nonmarital pregnancy but do
      increase the likelihood that such a pregnancy will end in abortion or a
      nonmarital birth rather than in a marital birth. CONCLUSIONS: The characteristics
      of teenage women and their partners appear to play a role in nonmarital teenage
      pregnancy and its outcome. However, the estimated relationships between one
      partner's characteristics and the probability of a nonmarital pregnancy and its
      resolution are generally little affected by whether the other partner's
      characteristics are also taken into account.

PMID- 11589540
TI  - Timing of alcohol and other drug use and sexual risk behaviors among unmarried
      adolescents and young adults.
AB  - CONTEXT: Although alcohol and drug use by young people has been associated with
      sexual risk behavior in some research, detailed data are lacking on the timing of
      substance use in relationship to sexual risk-taking. METHODOLOGY: Cross-sectional
      data on 7,441 unmarried young people aged 14-22 from the 1992 Youth Risk Behavior
      Survey (household supplement) were used in the analysis. Alcohol and other drug
      use at last sexual intercourse, substance use in the past 30 days (recent use),
      the number of different substances ever used (lifetime use) and age at initiation
      of alcohol use are examined here. The outcome variables assessed through
      multivariate regression analyses were condom use at last intercourse and more
      than one sexual partner in the past three months. RESULTS: Failure to use a
      condom was strongly associated with the lifetime substance-use scale or,
      alternatively, with age at initiation of alcohol. Once the number of substances
      ever used was controlled for, neither substance use at last sexual intercourse
      nor recent use was associated with the likelihood of using a condom at last
      coitus. Among young men and women, recent substance use and use of either alcohol
      or drugs at last intercourse were both strongly associated with having had more
      than one sexual partner in the past three months. For females only, lifetime use
      also increased the probability of recent multiple partners. CONCLUSIONS: The
      relationships between alcohol and other drug use and two sexual behaviors--condom
      use and multiple partners-suggest distinct mechanisms of influence and the need
      for different prevention strategies.

PMID- 11589541
TI  - Adverse childhood experiences and sexual risk behaviors in women: a retrospective
      cohort study.
AB  - CONTEXT: Adverse childhood experiences such as physical abuse and sexual abuse
      have been shown to be related to subsequent unintended pregnancies and infection
      with sexually transmitted diseases. However, the extent to which sexual risk
      behaviors in women are associated with exposure to adverse experiences during
      childhood is not well-understood. METHODS: A total of 5,060 female members of a
      managed care organization provided information about seven categories of adverse
      childhood experiences: having experienced emotional, physical or sexual abuse; or
      having had a battered mother or substance-abusing, mentally ill or criminal
      household members. Logistic regression was used to model the association between
      cumulative categories of up to seven adverse childhood experiences and such
      sexual risk behaviors as early onset of intercourse, 30 or more sexual partners
      and self-perception as being at risk for AIDS. RESULTS: Each category of adverse
      childhood experiences was associated with an increased risk of intercourse by age
      15 (odds ratios, 1.6-2.6), with perceiving oneself as being at risk of AIDS (odds
      ratios, 1.5-2.6) and with having had 30 or more partners (odds ratios, 1.6-3.8).
      After adjustment for the effects of age at interview and race, women who
      experienced rising numbers of types of adverse childhood experiences were
      increasingly likely to see themselves as being at risk of AIDS: Those with one
      such experience had a slightly elevated likelihood (odds ratio, 1.2), while those
      with 4-5 or 6-7 such experiences had substantially elevated odds (odds ratios,
      1.8 and 4.9, respectively). Similarly, the number of types of adverse experiences
      was tied to the likelihood of having had 30 or more sexual partners, rising from
      odds of 1.6 for those with one type of adverse experience and 1.9 for those with
      two to odds of 8.2 among those with 6-7. Finally, the chances that a woman first
      had sex by age 15 also rose progressively with increasing numbers of such
      experiences, from odds of 1.8 among those with one type of adverse childhood
      experience to 7.0 among those with 6-7. CONCLUSIONS: Among individuals with a
      history of adverse childhood experiences, risky sexual behavior may represent
      their attempts to achieve intimate interpersonal connections. Having grown up in
      families unable to provide needed protection, such individuals may be unprepared
      to protect themselves and may underestimate the risks they take in their attempts
      to achieve intimacy. If so, coping with such problems represents a serious public
      health challenge.

PMID- 11589542
TI  - Choice of and satisfaction with methods of medical and surgical abortion among
      U.S. clinic patients.
AB  - CONTEXT: Abortion induced by drugs is now a viable alternative to surgically
      induced abortion for U. S. women. Women's willingness to use these new methods of
      medical abortion hinges on the extent to which they prove acceptable, however.
      METHODS: Among 304 women participating in a clinical trial of medical abortion,
      186 received a methotrexate-induced abortion and 118 were offered the option of a
      medical abortion but chose a surgical procedure instead. Study participants
      completed self-administered questionnaires before the abortion and again at a
      follow-up visit. RESULTS: Women in the medical and surgical abortion groups did
      not differ significantly with regard to demographic and other background
      characteristics: Their mean age was about 27, more than two-thirds were white,
      and three-quarters were unmarried and worked either part-time or full-time.
      However, women's ratings of seven attributes of abortion methods were significant
      predictors of choosing a medical abortion: Women were more likely to choose
      medical abortion if they placed greater importance on a method that was
      nonsurgical, one that resembled a miscarriage or one that could take place at
      home (odds ratios, 2.0-3.3). Conversely, women were less likely to choose medical
      abortion if they valued methods that were quick, that did not involve painful
      cramping or seeing blood or blood clots and that needed a doctor or nurse to be
      present (odds ratios, 0.3-0.5). Compared with those who had a surgical abortion,
      women who had a methotrexate-induced abortion expected more bleeding (mean
      scores, 3.5 vs. 3. 1) and reported more pain (3.4 vs. 2.9), heavier bleeding (3.4
      vs. 2.5) and bleeding of longer duration (3.3 vs. 2.6). The overwhelming majority
      of women in the medical and surgical abortion groups reported that they were
      either very or somewhat satisfied with their abortion method (81% and 82%,
      respectively), would recommend it to others (82% and 78%) and would choose the
      method again (89% and 93%). CONCLUSIONS: Factors affecting the choice of abortion
      method appear to be numerous and complex. Providers need to be sensitive to
      differences in women's values and life circumstances when counseling them about
      an abortion method. In particular, providers should incorporate into their
      counseling sessions what women need to know about the characteristics of abortion
      methods and help women to identify what is the best option for them.

PMID- 11589543
TI  - Childbearing in cohabiting unions: racial and ethnic differences.
AB  - CONTEXT: Cohabitation provides a two-parent family union in which to have and
      raise children outside of marriage. Little is known, however, about the
      conditions under which cohabiting couples conceive and decide to have children.
      METHODS: The National Survey of Family Growth provides detailed data on the
      cohabitation and fertility histories of American women. Life-table techniques,
      event-history analyses and logistic regression were employed to understand the
      racial and ethnic differences in the timing of childbearing within cohabiting
      unions and whether childbearing within cohabiting unions is more acceptable to
      members of minorities than to whites. RESULTS: In multivariate models, Hispanic
      women were found to be 77% more likely than white women to conceive a child in
      cohabitation and black women were 69% more likely than white women to do so.
      Among women who became pregnant while cohabiting, Hispanic women were almost
      twice as likely and black women were three times as likely as white women to
      remain cohabiting with their partner when their child was born. In addition,
      children born to Hispanic women in cohabiting unions were found to be 70% more
      likely to be intended than were those born to cohabiting white women.
      CONCLUSIONS: In terms of fertility, cohabitation does not maintain the same place
      in the American family system for all racial and ethnic groups. These racial and
      ethnic differences in fertility-related behavior are not explained by
      socioeconomic differences. Based on levels of childbearing during cohabitation,
      relationship status at time of birth and intention status of children, it appears
      that cohabitation is a more acceptable arena for family building among Hispanic
      women than among whites or blacks.

PMID- 11589544
TI  - The influence of significant others on Australian teenagers' decisions about
      pregnancy resolution.
AB  - CONTEXT: Teenagers' decisions about how to resolve a pregnancy are made in the
      context of a society, a family and a relationship with a partner. Little is known
      about how such decisions are made, however, particularly in Australia. METHODS:
      The association between the influence--both direct and indirect--of significant
      others and adolescent women's decisions to terminate or continue a pregnancy is
      examined here using data from a case-control study on 1,324 pregnant teenagers in
      Australia. Bivariate analyses were used to explore the association between
      pregnancy resolution and direct or indirect influence toward abortion or birth.
      Multivariate logistic regression analyses were used to model the association
      between significant others' influence and teenagers'pregnancy resolution
      decisions while controlling for adolescent women's background characteristics.
      RESULTS: Teenagers who reported that their partner influenced them toward
      abortion had significantly increased odds of choosing abortion (10.4), and those
      whose partner influenced them toward motherhood had significantly reduced odds of
      choosing abortion (0.5). Direct influence from parents toward either abortion or
      motherhood was not significantly associated with teenagers' decisions. Mothers
      are an important source of indirect influence, however: Teenagers whose mother
      had become a mother as a teenager had reduced odds of choosing abortion (0.4),
      and those whose mother had ever had an abortion had increased odds of choosing
      abortion (2. 1). Teenagers who had a sister who had ever had an abortion had
      significantly increased odds of choosing abortion (2.4). CONCLUSION: While most
      young women report they were not directly influenced by a significant other in
      their decision to continue or terminate a pregnancy, pregnancy resolution
      decisions are affected by families and partners, often indirectly. These findings
      have important implications for the manner in which services are delivered to
      these young women.

PMID- 11589545
TI  - The NIH condom report: the glass is 90% full.

PMID- 11589546
TI  - The IUD and recovery of fertility.

PMID- 11589547
TI  - Interactions between yeasts and bacteria in the smear surface-ripened cheeses.
AB  - In the initial phase of ripening, the microflora of bacterial smear surface
      ripened cheeses such as Limburger, Taleggio, Brick, Munster and Saint-Paulin and
      that of surface mould-ripened cheeses such as Camembert and Brie may be similar,
      but at the end of the ripening, bacteria such as Brevibacterium spp.,
      Arthrobacter spp., Micrococcus spp., Corynebacterium spp. and moulds such as
      Penicillium camemberti are, respectively, the dominant microorganisms. Yeasts
      such as Candida spp., Cryptococcus spp., Debaryomyces spp., Geotrichum candidum,
      Pichia spp., Rhodotorula spp., Saccharomyces spp. and Yarrowia lipolytica are
      often and variably isolated from the smear surface-ripened cheeses. Although not
      dominant within the microorganisms of the smear surface-ripened cheeses, yeasts
      establish significant interactions with moulds and especially bacteria, including
      surface bacteria and lactic acid bacteria. Some aspects of the interactions
      between yeasts and bacteria in such type of cheeses are considered in this paper.

PMID- 11589548
TI  - Saccharomyces cerevisiae as a starter culture in Mycella.
AB  - The potential use of Saccharomyces cerevisiae FB7 as an additional starter
      culture for the production of Mycella, a Danish Gorgonzola type cheese, was
      investigated. Two dairy productions of Mycella, each containing batches of
      experimental cheeses with S. cerevisiae added and reference cheeses without yeast
      added were carried out. For both experimental and reference cheeses, chemical
      analysis (pH, a(w), NaCl, water and fat content) were carried out during the
      ripening period, but no significant differences were found. The evolution of
      lactic acid bacteria was almost identical in both the experimental and reference
      cheeses and similar results were found for the number of yeast. S. cerevisiae FB7
      was found to be predominant in the core of the experimental cheeses throughout
      the ripening period, while Debaryomyces hansenii dominated in the reference
      cheese and on the surface of the experimental cheeses. In the cheeses with S.
      cerevisiae FB7, an earlier sporulation and an improved growth of Penicillium
      roqueforti was observed compared to the reference cheeses. Furthermore, in the
      experimental cheese, synergistic interactions were also found in the aroma
      analysis, the degradation of casein and by the sensory analysis. The observed
      differences indicate a positive contribution to the overall quality of Mycella by
      S. cerevisiae FB7.

PMID- 11589549
TI  - DNA typing methods for differentiation of Debaryomyces hansenii strains and other
      yeasts related to surface ripened cheeses.
AB  - The discriminative power of ITS-PCR, ITS-PCR RFLP and mitochondrial (mt)-DNA RFLP
      were evaluated for differentiation of yeasts of importance for surface ripened
      cheeses. In total 60 isolates were included. Of these, 40 strains of the
      following species, Debaryomyces hansenii var. hansenii, D. hansenii var. fabryi,
      Saccharomyces cerevisiae, Candida zeylanoides, Kluyveromyces lactis and Yarrowia
      lipolytica, were obtained from culture collections and 20 isolates of D. hansenii
      representing six different phenotypes were collected from seven Danish producers
      of surface ripened cheeses. ITS-PCR was evaluated for differentiation at species
      level on the 40 strains obtained from culture collections. Ten strains of each
      variety of D. hansenii and five strains of each of the above mentioned species
      were analysed. For each of the investigated species, a specific ITS1-5.8S rDNA
      ITS2 region size was observed. Accordingly ITS-PCR was found valuable for
      differentiation at species level of yeasts of importance for surface ripened
      cheeses. ITS-PCR RFLP was investigated for the purpose of strain typing of D.
      hansenii. Ten CBS strains of each variety of D. hansenii were analysed. Only one
      enzyme (TaqI) out of several investigated (BamHI, DpnI, Fnu4HI, HaeIII, HindIII,
      HpaII, NlaII, Sau3AI, TaqI) demonstrated genetic diversity within the strains.
      This enzyme divided the 20 strains in three groups. Sequence analysis of the ITS1
      5.8S rDNA-ITS2 region for the type strains of each variety of D. hansenii showed
      an identity of 99.84%, corresponding to a difference in one basepair. Based on
      these results, ITS-PCR RFLP was found ineffective for strain typing of D.
      hansenii. MtDNA RFLP using HaeIII and HpaII was evaluated for strain typing of D.
      hansenii on the 20 CBS strains of D. hansenii. The CBS strains were divided into
      16 groups according to their restriction profiles, which proved the method useful
      for typing of D. hansenii at subspecies level. The 20 dairy isolates showed a
      lower genetic variability than the CBS strains as they were divided into eight
      groups. Cluster analysis of the 20 CBS strains and the 20 dairy isolates based on
      their mtDNA restriction profiles showed (max. similarity level = 52%) that the
      dairy isolates only clustered with the CBS strains of D. hansenii var. hansenii.
      For some of the dairies more than one strain of D. hansenii were found to be
      involved in the ripening process, indicating that the method could be useful for
      subspecies typing and investigation of the microbial succession between strains
      of D. hansenii during the ripening process of surface ripened cheeses.

PMID- 11589550
TI  - Use of Fourier transform infrared spectroscopy to evaluate the proteolytic
      activity of Yarrowia lipolytica and its contribution to cheese ripening.
AB  - The purpose of this study was to investigate the suitability of Fourier transform
      infrared (FTIR) spectroscopy as rapid technique to be used to investigate the
      secondary structure of proteins in aqueous solution and its changes as a
      consequence of microbial proteolytic activity as well as to assess or identify
      the contribution of different strains of Yarrowia lipolytica to cheese ripening.
      The comparison of spectroscopic data with SDS-polyacrylamide gel electrophoresis
      (PAGE) electrophoretograms outlined the consistency between the two instrumental
      approaches and showed a remarkable biodiversity between strains of Y. lipolytica.
      The strains tested were shown to modify the secondary structure of the caseins,
      inducing transitions between alpha helix and beta sheets, thus confirming the
      ability of this species to hydrolyse alphaS1 casein "in vitro" and to induce
      protein breakdown in skim milk, although strong heterogeneity in the hydrolytic
      activity of the strains was observed. Significant differences in the Amide I and
      Amide II bands of protein of curds and cheeses obtained from milk inoculated with
      Lactococcus lactis subsp. lactis and different strains of Y. lipolytica occurred
      during ripening. Y. lipolytica Y3 presented the most relevant enzymatic activity
      inducing transitions between alpha helix and beta sheets of proteins, as
      evidenced by the strong absorbance reduction of the Amide I band and the increase
      of the Amide II band. In the control and in the samples inoculated with the Y.
      lipolytica strains PO1 and RO13 changes resulted in a strengthening of the
      interactions with solvent molecules and of the hydration state of the caseins.

PMID- 11589551
TI  - Some probiotic properties of yeast isolates from infant faeces and Feta cheese.
AB  - Yeast isolates from infant faeces and Feta cheese were characterized to species
      level by phenotypic criteria, Randomly Amplified Polymorphic DNA (RAPD)-PCR and
      mitochondrial DNA (mt-DNA) restriction analysis. Results suggested that there is
      a good agreement between phenotypic characterization of yeasts and RAPD-PCR at
      species level; in addition, RAPD-PCR as well as mt-DNA restriction analysis
      provided good discrimination at strain level. Some technological and probiotic
      properties of selected strains were also investigated. The test strains exhibited
      lipolytic and proteolytic activities. They also tolerated low pH and survived
      satisfactory in gastric juice in vitro as well as in the presence of bile. In
      general, the isolates from faeces were more resistant to low pH and bile than
      those from Feta cheese. Selected strains could be used as starter supplements for
      industrial fermentations.

PMID- 11589552
TI  - Identification and biochemical characteristics of yeast microflora of Rokpol
      cheese.
AB  - Yeast microflora on the surface and interior of Rokpol cheese was examined for
      cheeses produced at three dairies located in Lower Silesia, Poland. Yeast
      populations on the surface of the cheeses ranged from 10(5)-10(9) cfu/g, but were
      10-100 times lower for interior samples. The occurrence and proportions of yeast
      species varied, depending on the dairy plant and cheese sample. The most
      frequently isolated species were: Candida famata and C. spherica, followed by C.
      intermedia and Geotrichum sp. Other species such as Saccharomyces kluyveri, C.
      kefyr and C. lipolytica were found occasionally. Extracellular and intracellular
      proteolytic and lipolytic activities were examined for 39 isolates of C. famata.

PMID- 11589553
TI  - Survey on mycoflora of cow and buffalo dairy products from Southern Italy.
AB  - Economic losses of dairy products due to spoilage by yeasts have been increasing
      in European companies because of the reduced use of preservatives, packaging in
      modified atmospheres, or new formulations that do not strictly control the growth
      of these organisms. This study reports the results of a survey of yeast species
      and populations in 145 samples of cow and buffalo dairy products collected in
      some regions of Southern Italy. Yeasts were isolated from 74% and 57% of cow and
      buffalo products, respectively. Candida inconspicua was the predominant species
      in unripened products from cow's milk, while C. famata was detected in medium and
      long-term ripened dairy products, mostly in association with other yeasts and
      with moulds belonging to the genus Penicillium. For dairy products produced from
      buffalo milk, C. inconspicua was the most important yeast frequently isolated
      from dairy products. Total yeast populations ranged from 5 x 10(2) to 5 x 10(5)
      cfu/g, indicating a good hygienic quality of the products. The isolation of C.
      albicans from one stracciatella sample is noteworthy, as this yeast represents a
      potential contamination by human. Even though yeasts are considered as
      environmental contaminants, the occurrence of some of them in dairy products at
      high levels could represent a risk for human health, in particular for
      immunocompromised patients.

PMID- 11589554
TI  - Occurrence and characterization of yeasts isolated from milks and dairy products
      of Apulia region.
AB  - One hundred and five strains of yeasts isolated from milk of different animal
      origin and from typical Apulian cheeses were studied to identify and characterize
      yeast strains for further selection as starter cultures for cheese production.
      The most prevalent isolates belonged to the species Trichosporon cutaneum
      (15.24%), Candida catenulata (10.48%) and Yarrowia lipolytica (8.57%). In order
      to evaluate the potential use as starter cultures, the occurrence of some
      selected properties, such as fermentation of glucose and lactose, assimilation of
      lactic acid, citric acid and lactose, growth at 4 degrees C and production of
      lipolytic and proteolytic enzymes in the strains belonging to the most frequent
      species was tested. C. catenulata and C. zeylanoides were positive for
      assimilation of lactic and citric acids and showed psychrotrophic aptitude. T.
      cutaneum was positive for all properties tested except for glucose and lactose
      fermentations. Y. lipolytica was endowed with remarkable lipolytic activity also
      at 4 degrees C and was positive for assimilation of lactic and citric acids,
      growth at 4 degrees C and proteolytic activity.

PMID- 11589555
TI  - Yeast populations in Sardinian feta cheese.
AB  - In this study, the yeast populations in feta cheese from two different Sardinian
      dairies were examined. Samples of good quality feta (32) and samples of feta with
      a slimy surface defect (10) were examined from Dairy A. Similar, samples of good
      quality feta (23), feta with slimy surface defects (14) and samples with swelling
      defects (6) were examined from Dairy B. Kluyveromyces lactis was the dominating
      species in feta from Dairy A (95.2% of samples) followed by Debaryomyces hansenii
      (76.2%), Dekkera anomala (28.6%) and Dek. bruxellensis (19%). D. hansenii was
      dominant in samples from Dairy B (93%), followed by K. lactis (23.3%), Geotrichum
      candidum (23.3%) and Dek. anomala (18.6%). No significant difference was observed
      between the occurrence of yeast species in feta of good quality and in feta with
      slimy surface defects, thus confirming that slimy production is not associated
      with yeast contaminations. The swelling of samples observed in Dairy B seems to
      be caused by Dek. anomala. In fact, this strong fermenting species was present in
      all swelled samples in numbers exceeding 10(6) CFU g(-1), while it was isolated
      in very low concentration in only 5.4% of good samples.

PMID- 11589556
TI  - Identification of fungi from dairy products by means of 18S rRNA analysis.
AB  - The role of fungi as cause of spoilage of dairy products, such as cheese and
      yoghurt, has been clearly demonstrated. Despite of this, there is still a lack in
      rapid methods for the identification of food-associated fungi. In the course of
      the present work, molecular taxonomical techniques were developed and used to
      identify yeasts involved in the spoilage of yoghurt and moulds responsible for
      spoilage of vacuum-packaged hard cheese. Three methods for DNA extraction and
      purification were evaluated and the fungus-specific primers TR1 and TR2 were used
      to amplify a 581-bp fragment within the gene, coding for the small ribosomal
      subunit (18S rRNA) of fungi. The 18S rRNA sequence analysis of fungi isolated
      from yoghurt and packaged cheese allowed to identify yeast belonging to
      Zygosaccharomyces microellipsoides and moulds belonging to Penicillium
      chrysogenum and Cladosporium cladosporoides.

PMID- 11589557
TI  - The growth, properties and interactions of yeasts and bacteria associated with
      the maturation of Camembert and blue-veined cheeses.
AB  - The growth of yeasts and bacteria were monitored during the maturation of
      Camembert and blue-veined cheese produced in Australia. Yeasts were prominent
      throughout maturation, growing to 10(5)-10(9)/g, depending on the manufacturer.
      Debaryomyces hansenii predominated, but there were lesser, inconsistent
      contributions from Yarrowia lipolytica. Of the non-lactic acid bacteria,
      Acinetobacter species were significant during the maturation of Camembert but not
      blue-veined cheeses, and grew to 10(6)-10(8) cfu/g. Staphylococcus and
      Micrococcus species were consistently isolated from the cheeses with
      Staphylococcus xylosus growing to 10(5)-10(9) cfu/g, depending on the product.
      Lactic acid bacteria (10(7)-10(9) cfu/g) were present throughout maturation but
      were not identified. Interactions between the various yeasts and bacterial
      isolates were examined. Several strains of D. hansenii exhibited killer activity
      but not against Y. lipolytica. None of the yeasts were antagonistic towards the
      bacteria but some strains of D. hansenii enhanced the growth of Y. lipolytica and
      S. xylosus. The yeast and bacterial isolates exhibited various degrees of
      extracellular proteolytic and lipolytic activities.

PMID- 11589558
TI  - The interaction between yeasts and bacteria in dairy environments.
AB  - The general environment from which raw dairy products originate and the
      microbiological quality of the products in its processed state inevitably admit
      yeast growth and spoilage. Only part of the primary microflora survives under the
      selective pressures exerted by the intrinsic and extrinsic biotic factors
      present, processing procedures and preservatives. Yeasts that possess the proper
      physiological attributes to counteract the specific ecological determinants will
      be favored. Eventually, a particular yeast community will develop, and if the
      environmental factors permit, this characteristic yeast community will result in
      a specific association contributing positively or negatively to the final
      product. The association that develops between yeasts and bacteria is governed by
      specific key properties selecting for a few predominant yeasts. These yeasts may
      either stimulate or inhibit normal bacterial growth. The extent to which
      interaction between yeasts and bacteria contribute to the final product is
      discussed.

PMID- 11589559
TI  - Yeasts from Water Buffalo Mozzarella, a traditional cheese of the Mediterranean
      area.
AB  - Countries of the Mediterranean area are characterized by production of artisanal
      cheeses, obtained from goat, sheep, cow and buffalo raw milk. The numbers and
      species of yeasts in the different cheeses are variable, but some species are
      more frequently detected than others. Kluyveromyces marxianus, K. lactis with
      their anamorph, Candida kefir, Debaryomyces hansenii and C. famata, C.
      colliculosa and C. catenulata are dominant species in several cheeses. However,
      Saccharomyces cerevisiae is often detected in pasta filata cheeses, such as Water
      Buffalo Mozzarella (WBM) or Cacio Cavallo Podolico. Recently, a comprehensive
      study of yeasts isolated from Mozzarella cheese produced in Basilicata (Southern
      Italy) has been carried out. The study has focused on lactose and/or galactose
      fermenting species (Kluyveromyces and Saccharomyces) to evaluate their role on
      the functional and sensory properties of the product. End products in milk were
      evaluated and the biodiversity in terms of production of sulphur dioxide, higher
      alcohols, ethyl acetate, and acetaldehyde was studied. In particular, S.
      cerevisiae strains from Water Buffalo Mozzarella cheese, compared to strains
      isolated from different habitats, such as wine, exhibited considerable difference
      in the production of some volatile compounds. The diversity observed could be
      related to the particular microhabitat of S. cerevisiae occurring in whey cheese
      of water buffalo milk.

PMID- 11589560
TI  - Yeasts associated with Sardinian ewe's dairy products.
AB  - In the present work, the occurrence of yeasts in different types of typical
      Sardinian ewe's cheeses (32 samples of pecorino, 32 of caciotta, 40 of feta, 56
      of ricotta) was determined. For the strains isolated the following properties
      were studied: proteolytic and lipolytic activities, the ability to grow at
      different temperatures, different concentrations of salt, and to assimilate
      and/or ferment compounds like lactate, citrate, lactose, glucose, galactose,
      lactic acid. Of 160 samples analysed, 76.2% yielded growth of yeasts. Yeast
      counts showed a certain variability among the samples. The highest levels were
      observed in caciotta and feta cheeses. A total of 281 strains belonging to 16
      genera and 25 species were identified. In general, Debaryomyces hansenii was the
      dominant species, representing 28.8% of the total isolates. Other frequently
      appearing species were Geotrichum candidum, Kluyveromyces lactis and K.
      marxianus. Other genera encountered were Pichia, Candida, Dekkera, Yarrowia and
      Rhodotorula. With regard to the biochemical and technological properties of the
      yeasts, only K. lactis, K. marxianus and Dek. anomala assimilated and fermented
      lactose, whereas the majority of the species assimilated lactic acid. The
      assimilation of citrate was a characteristic of D. hansenii, R. rubra and Y.
      lipolytica. On the whole, the yeasts were weakly proteolytic while lipolytic
      activity was present in several species. A high percentage of strains showed a
      certain tolerance to low temperatures while only some strains of D. hansenii and
      K. lactis were able to grow at a 10% NaCl concentration.

PMID- 11589561
TI  - Taxonomical and technological characteristics of Saccharomyces spp. associated
      with blue veined cheese.
AB  - In blue veined cheeses, the dominant yeast species in most cases is Debaryomyces
      hansenii. Saccharomyces spp. occurs less frequently, but they can be found in
      some blue veined cheeses. In the present study, the taxonomy of Saccharomyces
      spp. associated to blue veined cheeses was studied and comparisons made to type
      strains of Saccharomyces spp. and starter cultures of Saccharomyces spp. used in
      other food fermentations. Phenotypically, the cheese strains were referred to the
      Saccharomyces sensu stricto complex and were further identified as S. cerevisiae.
      Genotypically, the Saccharomyces spp. investigated were similar although
      chromosomal polymorphism were observed. Concerning the technological
      characteristics, they were similar in assimilation and fermentation of the
      residual sugars and organic acids naturally found in cheese. The investigated
      yeasts were also similar in their lipolytic activity being able to hydrolyse
      tributyrin and low chain (C:8), but not C:14 fatty acids. However, they differed
      in their tolerance to NaCl with the blue cheese strains showing a higher
      tolerance. The cheese strain S. cerevisiae FB 7 was the only yeast capable of
      degrading casein. It mainly degraded the alpha(s1)-casein and the beta(alpha2)
      casein components. It was also the only isolate stimulating the development of
      Penicillium roqueforti in cheese agar imitating the conditions in blue veined
      cheese. The stimulation of P. roqueforti was most pronounced for the least
      proteolytic strain of P. roqueforti examined.

PMID- 11589562
TI  - Proteolytic, lipolytic and molecular characterisation of Yarrowia lipolytica
      isolated from cheese.
AB  - This work studied the qualitative and quantitative proteolytic and lipolytic
      activities of Yarrowia lipolytica strains isolated from two cheese types.
      Randomly amplified polymorphic DNA-PCR (RAPD-PCR) analysis was used to compare
      the cheese strains of Y. lipolytica with strains isolated from other food
      products and with the type strain of the species in order to investigate the
      genetic diversity and occurrence of specific environmental groups. Diversity of
      proteolytic and especially lipolytic activity within Y. lipolytica strains
      isolated from dairy products was observed. In particular, the degree of
      specificity for saturated or unsaturated fatty acids as well as for even- or odd
      numbered carbon free fatty acids (FFAs) varied among the strains. The RAPD-PCR
      profiles showed low genetic relatedness between many of the food isolates and the
      type strain of the species. Such genetic variability needs to be further
      evaluated. Most of the Y. lipolytica strains appeared to be specific to the
      particular environment from which they were isolated. However, phenotypic
      characteristics having technological importance in dairy products and,
      particularly, lipolytic activities did not correspond to the genetic differences
      observed by RAPD-PCR analysis.

PMID- 11589563
TI  - Variability of the lipolytic activity in Yarrowia lipolytica and its dependence
      on environmental conditions.
AB  - This work was aimed to the evaluation of the variability of lipolytic activity in
      Yarrowia lipolytica strains, as well as to asses for a selected strain, the
      response to the changes of physico-chemical variables (such as pH, NaCl and lipid
      content), in order to obtain predictive models describing their effects on the
      lipolysis pattern. The strains tested, having different environmental origin,
      showed different patterns of the free fatty acids (FFA) released. The clustering
      of the free fatty acids profiles evidenced that the unweighted average distance
      within the strains of the same species did not exceeded 30%. However, the
      lipolytic activity of some strains generated FFA profiles that differentiated
      from the majority of the strains considered. Also, when a single strain was
      inoculated in model systems in which pH, NaCl and milk fat were modulated
      according to a Central Composite Design (CCD), chemico-physical characteristics
      of the system led to marked variations in the lipolytic activity with consequent
      changes in individual fatty acids released. In most cases, when the same Y.
      lipolytica strain was used, under the experimental conditions adopted, the
      modulation of the lactic acid, NaCl and lipid content did not generate
      differences in the fatty acid release exceeding 20-21%. However, some
      combinations of factors remarkably affected lipase expression or activity, and
      generated differences in the fatty acid released higher than those observed among
      different strains of the same species.

PMID- 11589564
TI  - Contribution of Gal- lactic acid bacteria to Saccharomyces cerevisiae metabolic
      activity in milk.
AB  - The contemporaneous presence of Streptococcus thermophilus and Lactobacillus
      delbrueckii subsp. bulgaricus affected the growth kinetics of Saccharomyces
      cerevisiae PZ2 and the metabolic products of their growth were quantitatively and
      qualitatively different from those produced by single strains inoculated alone.
      S. cerevisiae can grow in milk without using lactose or galactose. In particular,
      the presence of peptides seems to be sufficient to ensure its growth. The growth
      of S. cerevisiae with lactic acid bacteria is characterised by stimulatory
      effects that involve both yeast and bacteria. However, the release of galactose
      by lactic acid bacteria does not seem to be the core metabolic event of these
      stimulatory effects on S. cerevisiae.

PMID- 11589565
TI  - Tagged Transcriptome Display (TTD) in indica rice using Ac transposition.
AB  - We have developed a population of transgenic indica rice lines containing the
      autonomous Activator transposon (Ac) from maize. A transposon excision assay
      using as the reporter the green fluorescent protein (GFP) gene driven by the
      ubiquitin promoter was used to monitor Ac excision in various tissues. Our
      results, based on Ac excision and re-insertion events in 289 independent rice
      transformants, provide an insight into transposon biology in this heterologous
      model cereal system. Twenty percent of the transformed calli displayed uniform
      GFP activity, indicating very early Ac excision, while later excision in another
      40% of calli was revealed by mosaic GFP activity. Both phenotypes were confirmed
      by molecular analysis. Progeny analysis revealed active transposition, with some
      lines displaying transposition to unlinked positions. Amplification of the Ac
      copy number was observed in approximately 30% of the lines, thus tagging multiple
      sites. We developed a "transposon insertion display" procedure, involving the use
      of CpG methylation-sensitive enzymes and a macroarray-based approach with cDNA as
      a complex hybridization probe, to selectively detect transposon insertions in
      transcribed sequences. Sequencing of tagged sites identified by hybridization to
      leaf cDNA revealed that all the hybridizing tags were homologous to genes or ESTs
      present in databases. Extrapolation from these data suggests that 12% of all
      amplified tags display homology to genes or ESTs - five times more than would be
      expected on the basis of random transpositional insertion. This Tagged
      Transcriptome Display (TTD) technique, using a population of Ac insertion-tagged
      lines, therefore represents a convenient approach for the identification of
      tagged genes involved in specific processes, as revealed by their expression
      patterns.

PMID- 11589566
TI  - A mutation in the GTPase domain of the large subunit rRNA is involved in the
      suppression of a -1T frameshift mutation affecting a mitochondrial gene in
      Chlamydomonas reinhardtii.
AB  - The dum19 mutation isolated in Chlamydomonas reinhardtii is due to the deletion
      of one T at codon 152 of the mitochondrial cox1 gene sequence. Phenotypically,
      the dum19 mutant is characterized by a lack of cytochrome c oxidase activity and
      is unable to grow under heterotrophic conditions. A spontaneous pseudo-revertant
      that grows slowly in the dark was isolated from the dum19 mutant strain. A
      genetic and molecular analysis allowed us to demonstrate that the revertant
      phenotype is the consequence of two additional mutations that together act as a
      frameshift suppressor: an m mutation affecting a mitochondrial gene other than
      cox1 and an n mutation affecting a nuclear gene. On its own the n mutation does
      not act as a suppressor, whereas the m mutation very slightly compensates for the
      effect of the -1T mutation. Sequencing analysis showed that the m mutation
      affects the GTPase-associated domain of the large subunit (LSU) ofmitochondrial
      rRNA. Surprisingly, two substitutions, A1090 to G and A1098 to C, were found in
      the LSU rRNA of the revertant, the latter one being already present in the dum19
      mutant strain itself. The A1090 to G substitution is thus involved in the
      suppression of the frameshift mutation, but it is not clear whether the change at
      position 1098 is also required for the expression of the suppressed phenotype. To
      our knowledge, this is the first example of a mutation in the GTPase-associated
      domain acting as a suppressor of a frameshift mutation.

PMID- 11589567
TI  - Structure of the telomeric ends of mt DNA, transcriptional analysis and complex I
      assembly in the dum24 mitochondrial mutant of Chlamydomonas reinhardtii.
AB  - The dum24 mutant of Chlamydomonas reinhardtii contains four types of altered
      mitochondrial linear genomes: two types of deleted monomers and two types of
      dimers resulting from fusions between some monomers via their deleted ends. All
      molecules lack at least cob, nd4 and the 3' end of nd5, three adjacent genes
      located in the left part of the genome. We present evidence showing that in
      dum24, as in other deletion mutants, the deletions extend to the left telomeric
      end, and propose that the only replicative forms in the mutants are the dimeric
      DNA molecules that possess intact telomeric structures at both ends. Two
      abnormally large transcripts produced from chimeric genes are detected in dum24,
      which throws some light on the location of potential promoter sequences and
      processing signals in the mitochondrial genome. Using BN-PAGE analysis and
      immunological methods to detect complex I, we further show that dum24
      mitochondria do not possess the normal multimeric complex I (850 kDa), but
      produce a smaller, partially assembled, complex (650 kDa), demonstrating a role
      for ND4 and/or ND5 subunits(s) in complex I assembly.

PMID- 11589568
TI  - Role of the kinetochore protein Ndc10 in mitotic checkpoint activation in
      Saccharomyces cerevisiae.
AB  - Mitotic checkpoints delay cell cycle progression in response to alterations in
      the mitotic apparatus, thus ensuring correct chromosome segregation. While
      improper spindle orientation activates the Bub2/Bfa1-dependent checkpoint in
      budding yeast, delaying exit from mitosis, lack of bipolar kinetochore
      microtubule attachment activates a signal transduction cascade that prevents both
      anaphase onset and exit from mitosis by inhibiting the Cdc20/APC (Anaphase
      Promoting Complex)-mediated proteolysis of securin and inactivation of mitotic
      cyclin-dependent kinases (CDKs), respectively. Proteolysis of the securin Pdsl is
      necessary to liberate the separase Esp1, which then triggers sister chromatid
      separation, whereas inactivation of mitotic CDKs is a prerequisite for exit from
      mitosis and for starting a new round of DNA replication in the next cell cycle.
      In budding yeast, this latter checkpoint response involves the proteins Mad1, 2,
      3, Bub1 and Bub3, whose vertebrate counterparts localize to unattached
      kinetochores. Mutations that alter other kinetochore proteins result in mitotic
      checkpoint activation, while the ndc10-1 mutation not only impairs kinetochore
      function, but also disrupts the checkpoint response, indicating a role for Ndc10
      in this process. Here we present evidence that Ndc10 is not part of the Bub2/Bfa1
      dependent pathway, and its role in the checkpoint response might also be
      different from that of the other Mad and Bub proteins. Indeed, Ndc10, unlike
      other mitotic checkpoint proteins, is not required for the mitotic block induced
      by overexpression of the Mpsl protein kinase, which is implicated in mitotic
      checkpoint control. Furthermore, the delay in mitotic exit caused by non
      degradable Pds1, which does not require Mad and Bub proteins, depends on Ndc10
      function. We propose that a pathway involving Ndc10 might monitor defects in the
      mitotic apparatus independently of the Mad and Bub proteins. Since the Espl
      separase is required for exit from mitosis in both ndc10-1 and nocodazole-treated
      mad2delta cells, the two signal transduction cascades might ultimately converge
      on the inactivation of Esp1.

PMID- 11589569
TI  - Genome-wide linkage analysis of Arabidopsis genes required for leaf development.
AB  - In most crop species, primary productivity depends mainly on the leaf. However,
      the genes that contribute to the making of plant leaves remain largely unknown.
      With a view to identifying the genes involved in leaf development in Arabidopsis
      thaliana, we previously isolated EMS-induced mutants with abnormally shaped
      leaves and demonstrated that they fall into 94 complementation groups. We present
      here the map positions of 76 of these genes, which have been obtained using a
      high-throughput genetic mapping method, based on the simultaneous coamplification
      by PCR of 21 polymorphic microsatellites and the semiautomated fluorescent
      detection of the products. The map positions and F2 mapping populations obtained
      in this work will be instrumental in the positional cloning of these genes, which
      are essential for leaf development.

PMID- 11589570
TI  - A scytalone dehydratase gene from Ophiostoma floccosum restores the melanization
      and pathogenicity phenotypes of a melanin-deficient Colletotrichum lagenarium
      mutant.
AB  - Scytalone dehydratase is involved in the production of fungal
      dihydroxynaphthalene (DHN) melanin. We have isolated and characterized OSD1, a
      gene encoding scytalone dehydratase from the sap-staining fungus Ophiostoma
      floccosum by PCR-based cloning. Sequence analysis suggests that the OSD1 gene
      encodes a protein of 216 amino acids with a molecular weight of 24.2 kDa that
      shows 51-70% sequence identity to other scytalone dehydratases. The cloned OSD1
      contains two introns of 76 bp and 63 bp in length, and is the longest scytalone
      dehydratase gene sequence so far reported. Transformation of a DHN melanin
      deficient, non-pathogenic, mutant of Colletotrichum lagenarium with the OSD1 gene
      restored melanin production and pathogenicity. The ability of the mutant to
      produce the OSD1 gene product was confirmed by RT-PCR analysis. These data show
      that the cloned OSD1 gene product can function in the DHN melanin biosynthetic
      pathway in C. lagenarium.

PMID- 11589571
TI  - Transcriptional activation of the human Cu/Zn superoxide dismutase gene by
      2,3,7,8-tetrachlorodibenzo-p-dioxin through the xenobiotic-responsive element.
AB  - Cu/Zn superoxide dismutase (SOD1) catalyzes the dismutation of superoxide
      radicals produced during biological oxidations and environmental stress. Here we
      have investigated the effect of the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD), on the promoter of the Cu/Zn superoxide dismutase (SOD1) gene in
      HepG2 and HeLa cells using the chloramphenicol acetyltransferase gene as a
      reporter. The SOD1 promoter was activated 4- to 5-fold by TCDD treatment, in a
      concentration-dependent manner. In addition, the level of SOD1 mRNA and the
      enzymatic activity of the SOD1 protein were also enhanced on exposure of the
      cells to TCDD. Functional analysis of the regulatory region of the SOD1 gene by
      deletion and point mutation, and the use of a heterologous promoter system,
      showed that the SOD1 gene was transactivated by TCDD via the xenobiotic
      responsive element (XRE). Gel mobility shift assays also confirmed the induction
      and the inducible binding of a receptor-ligand complex to XRE. Yeast cells that
      overexpress hSOD1 appeared to be more resistant to TCDD than the wild type. These
      results demonstrate that SOD1 is induced by TCDD via the XRE. The induced SOD1
      may accelerate the neutralization of the superoxide anion and thus reduce the
      oxidative damage associated with dioxin toxicity.

PMID- 11589572
TI  - Mutations in WSC genes for putative stress receptors result in sensitivity to
      multiple stress conditions and impairment of Rlm1-dependent gene expression in
      Saccharomyces cerevisiae.
AB  - Intracellular signaling by mitogen-activated protein (MAP) kinase cascades plays
      an essential role in the cellular response to environmental stress. In the yeast
      Saccharomyces cerevisiae, the PKC1-regulated, stress-activated MAP kinase
      pathway, the MPK1 cascade, is activated by heat and by a decrease in osmolarity.
      The genes WSC1, WSC2 and WSC3 encode putative receptors that maintain cell wall
      integrity under conditions of heat stress. Genetic studies place the function of
      the WSC genes upstream of the MPK1 kinase cascade. To further define the role of
      the WSC family in the stress response we determined whether: (1) the wscdelta
      mutants are sensitive to other environmental stress conditions, in addition to
      heat shock; (2) expression from four transcriptional control elements, known to
      be activated by stress, is impaired in wscdelta mutants; and (3) Wsc4, a Wsc
      homolog, has functions that overlap with those of the other Wsc family members.
      We report here that deletion of WSC and PKC1 causes hypersensitivity to ethanol,
      hydrogen peroxide and DNA-damaging drugs. In wscdelta mutants expression of beta
      galactosidase from the AP-1 response element (ARE), the heat shock response
      element (HSE) or the stress response element (STRE) is not reduced. In contrast,
      expression of a reporter gene placed under the control of the Rlm1 (transcription
      factor)-dependent response element is significantly reduced in wscdelta mutants.
      This suggests that the lysis defect of wscdelta mutants is at least in part
      caused by a defect in transcriptional regulation by Rlm1. Phenotypic analysis of
      the effect of deleting WSC4 in a wsc1delta mutant show that, unlike WSC2 or WSC3,
      deletion of WSC4 does not exacerbate the lysis defect of a wsc1delta strain. In
      contrast, deletion of WSC4 enhances the sensitivity of the wsc1delta mutant to
      heat shock, ethanol, and a DNA-damaging drug, suggesting that WSC4 plays a role
      in the response to environmental stress but that its function may differ from
      those of the other WSC family members.

PMID- 11589573
TI  - Overexpression of Bud5p can suppress mutations in the Gsp1p guanine nucleotide
      exchange factor Prp20p in Saccharomyces cerevisiae.
AB  - The gene product Prp20p, which is located in the nucleus, serves as the
      nucleotide exchange factor (GEF) for the small nuclear G protein Gsp1p in
      Saccharomyces cerevisiae, and catalyses the replacement of Gsp1-bound GDP by GTP.
      These proteins are involved in numerous cellular processes, including
      nucleocytoplasmic trafficking of macromolecules, cell cycle progression, DNA
      replication and maintenance of chromosome structure/stability. It is believed
      that in order to complete a full GDP/GTP cycle, Gsp1p has to shuttle between the
      nucleus and the cytoplasm, where its GTPase Activating Protein (GAP) Rna1p is
      located. Here, we report on the ability of Bud5p, the exchange factor for Rsr1p,
      to suppress conditional prp20 mutants when an extra copy of GSP1 is present. This
      suppression by BUD5 can be reversed by simultaneous overexpression of RNA1, and
      is not Rsr1p-dependent, nor allele-specific. We also show that Bud5p can
      physically interact with Gsplp, both in vitro and in vivo. These,findings raise
      the possibility that Bud5p could act as a cytoplasmic exchange factor for Gsp1p
      and, therefore, that a complete GDP/GTP cycle could take place in the cytoplasm.

PMID- 11589574
TI  - Nematode chitin synthases: gene structure, expression and function in
      Caenorhabditis elegans and the plant parasitic nematode Meloidogyne artiellia.
AB  - Although the presence of chitin in nematodes is well documented little is known
      about its synthesis in this phyletic group. The recently completed genome
      sequence of Caenorhabditis elegans predicts two sequences with homology to chitin
      synthases (chitin-UDP acetyl-glucosaminyl transferase; EC 2.4.1.16). We show that
      these genes are differentially expressed in a pattern that may reflect different
      functional roles. One gene is expressed predominantly in the adult hermaphrodite
      (the main egg-producing stage in the nematode) and later larval stages, which is
      consistent with a role in production of chitin for the eggshell. The other gene,
      however, is expressed in the cells that form the pharynx, and only in the period
      directly preceding a moult. These data suggest that the product of this gene is
      involved in synthesis of the feeding apparatus, which is replaced during each
      moult. We have also isolated a full-length genomic sequence of a chitin synthase
      orthologue from the plant parasitic nematode Meloidogyne artiellia. The single
      gene present in M. artiellia shows an expression pattern that is consistent with
      a role for the protein in production of the eggshell.

PMID- 11589575
TI  - Retrolyc1 subfamilies defined by different U3 LTR regulatory regions in the
      Lycopersicon genus.
AB  - Retrolycl, a Ty1/copia-like element, was originally isolated from the
      Lycopersicon peruvianum genome and shown to be present also in other Lycopersicon
      species. It shares extensive similarities with Tntl, except in its U3 regulatory
      region. In order to evaluate Retrolycl diversity, we analyzed partial sequences
      including both coding domains and the U3 regulatory region in four different
      species of the Lycopersicon genus. Two Retrolycl subfamilies defined by different
      U3 regions were identified. RetrolyclA is most abundant in L. peruvianum and L.
      hirsutum, while Retrolyc1B is distributed in all four species studied here. The
      RetrolyclA U3 region contains tandemly repeated elements of 53 bp. Transient
      expression analysis suggests that Retrolyc1A is a transcriptionally active
      family, and that the repeated motifs found in its U3 region are important
      transcriptional regulatory elements.

PMID- 11589576
TI  - Isolation of UV-induced mutations in the areA nitrogen regulatory gene of
      Aspergillus niger, and construction of a disruption mutant.
AB  - The areA gene of filamentous fungi encodes a positive-acting transcriptional
      factor required for the expression of genes involved in the utilisation of
      nitrogen sources other than ammonium and glutamine. In Aspergillus niger we have
      isolated three UV-induced areA mutants and constructed a well-defined disruption
      allele of the areA gene. The areA gene was genetically localised on Linkage Group
      III, 3.6 map units (m.u.) from bioA1 and 4.5 m.u. from lysA7. Analysis of the
      expression of the nitrate reductase encoding gene and of nitrate reductase
      activities show that the mutated areA strains behave as loss-of-function mutants
      and can be classified as areAr type. In addition, growth tests were performed
      using several nitrogen sources in combination with glucose. The results suggest
      that, unlike the case in A. nidulans, in A. niger the AreA protein also plays a
      role in the presence of ammonium. Furthermore, the spectrum of protease
      activities secreted by A. niger differs from that produced by A. nidulans, as
      only A. niger is able to degrade elastin.

PMID- 11589577
TI  - Cytochrome c is not essential for viability of the fungus Aspergillus nidulans.
AB  - The filamentous fungus Aspergillus nidulans is an obligate aerobe, which is
      capable of anaerobic survival, but not anaerobic growth. Since cytochrome c forms
      an essential part of the oxidative respiratory pathway it was expected that
      mutants lacking this component would be non-viable. Gene replacement of one
      homologue of the cycA (cytochrome c) gene was carried out in a diploid strain.
      Benomyl-induced haploidisation of this diploid yielded all cycA+ haploid
      colonies, initially suggesting that loss of cycA was indeed lethal. However, use
      of an alternative unbiased method to recover haploids yielded viable, but slow
      growing, cycA- mutants. Replacement of the cycA locus in the cycA- mutants was
      verified by Southern blotting. Spectral analysis confirmed the absence of
      detectable levels of cytochrome c, and respiratory insensitivity to cyanide
      suggested the absence of cytochrome c-dependent respiration. Growth parameters
      were consistent with those expected of a CycA- mutant. Compared to the wild type,
      the mutants grew slowly on fermentable carbon sources, did not grow on non
      fermentable carbon sources, and produced higher levels of ethanol. To our
      knowledge, this is the first report of a filamentous fungus that remains viable
      after complete elimination of a functional cytochrome c gene. We propose that the
      mutants are viable due to their ability to ferment and to use alternative
      respiratory pathways.

PMID- 11589578
TI  - The Hypocrea jecorina HAP 2/3/5 protein complex binds to the inverted CCAAT-box
      (ATTGG) within the cbh2 (cellobiohydrolase II-gene) activating element.
AB  - The 5' regulatory region of the chh2 gene, encoding cellobiohydrolase II, of the
      filamentous fungus Hypocrea jecorina contains the cbh2 activating element (CAE)
      which is essential for cbh2 expression. The CAE consists of two separate,
      adjacent motifs, a CCAAT box on the template strand (ATTGG) and a GTAATA box on
      the coding strand, which co-operate in the induction of the gene by cellulose or
      sophorose. EMSA supershift experiments using an antibody against Aspergillus
      nidulans HAPC suggested that the complex which binds to the H. jecorina CCAAT box
      contains a HAPC homolog. To obtain direct evidence for this, we have cloned the
      hap2, hap3 and hap5 genes from H. jecorina. They encode proteins whose core
      regions display great similarity to Aspergillus HAPB, HAPC and HAPE and to known
      HAP homologs from other organisms. All three genes are transcribed in a carbon
      source-independent manner. A. nidulans deltahap strains were functionally
      complemented in vitro by the overexpressed H. jecorina HAP2, HAP3 and HAP5
      proteins, and they thus represent subunits of the CCAAT-binding complex.
      Furthermore, all three proteins (HAP2, HAP3 and HAP5) were needed to bind to the
      CAE in the H. jecorina cbh2 gene promoter in vitro. We conclude that the CCAAT
      box on the template strand in CAE is bound by the H. jecorina equivalent of the
      HAP protein complex.

PMID- 11589579
TI  - Molecular cloning, sequence analysis and expression of a novel gene induced by
      near-UV light in Bipolaris oryzae.
AB  - A cDNA clone derived from a novel gene (uvi-1) that is inducible by near-UV light
      was isolated by a differential screening procedure from a cDNA library of the
      fungus Bipolaris oryzae and characterized further. Sequence analysis of the clone
      revealed that uvi-1 encodes a protein with a putative molecular mass of 17 kDa;
      the UVI-1 protein shows significant similarity to a putative protein encoded by a
      cDNA which is expressed during appressorium formation in the rice blast fungus,
      Magnaporthe grisea. The corresponding genomic clone was also isolated, and
      Southern analysis of genomic DNA indicated the presence of a single copy of the
      uvi-1 gene in B. oryzae. Northern analysis showed that the uvi-1 transcripts are
      induced by exposure to near-UV light, but not by blue or red light. Furthermore,
      accumulation of uvi-1 transcripts is observed during differentiation of the
      appressorium.

PMID- 11589580
TI  - DNA protection mechanisms are not involved in the radioresistance of the
      hyperthermophilic archaea Pyrococcus abyssi and P. furiosus.
AB  - Hyperthermophilic archaea of the genus Pyrococcus are resistant to gamma
      radiation, suggesting that efficient mechanisms for DNA repair exist in these
      organisms. To determine whether protective mechanisms might also be implicated in
      this radioresistance, we have estimated the linear density of DNA double-stranded
      breaks caused by gamma irradiation in the genomic DNA of two Pyrococcus species,
      using Escherichia coli and the radioresistant bacterium Deinococcus radiodurans
      as controls. The linear density of double-stranded breaks was essentially the
      same in all four microorganisms when irradiation was carried under similar
      anaerobic conditions, indicating that no specific DNA protection mechanisms exist
      in Pyrococcus species. Using one- and two-dimensional gel electrophoresis we
      compared the protein patterns from Pyrococcus abyssi and P. furiosus cells that
      had or had not been exposed to gamma rays. We did not detect any significant
      protein induction following DNA damage in either species.

PMID- 11589581
TI  - Lipopolysaccharide biosynthesis in Xanthomonas campestris pv. campestris: a
      cluster of 15 genes is involved in the biosynthesis of the LPS O-antigen and the
      LPS core.
AB  - As a result of mutational and DNA sequence analysis, a wxc gene cluster involved
      in the synthesis of the surface lipopolysaccharide (LPS) was identified in
      Xanthomonas campestris pv. campestris. This gene cluster comprises 15 genes. It
      was located on a cloned 35-kb fragment of chromosomal DNA, close, but not
      directly adjacent, to previously characterized genes for LPS biosynthesis. The G
      + C content of all but one of the wxc genes was atypically low for X. campestris
      pv. campestris, while the G + C distribution was uniform throughout the cluster.
      An SDS-PAGE analysis of mutant strains defective in various wxc genes confirmed
      that genes from this cluster were involved in LPS biosynthesis. The mutant
      phenotypes allowed the differentiation of three regions within the wxc cluster.
      Genes from wxc region 1 are necessary for the biosynthesis of the water-soluble
      LPS O-antigen. Analysis of DNA and deduced amino acid sequences led to the
      identification of two glycosyltransferases, two components of an ABC transport
      system, and a possible kinase among the seven putative proteins encoded by genes
      constituting wxc region 1. The two genes in wxc region 2 were similar to gmd and
      rmd, which direct the synthesis of the sugar nucleotide GDP-D-rhamnose. Mutations
      affecting wxc region 2 demonstrated its involvement in the formation of the LPS
      core. Genes from wxc region 3 showed similarities to genes that code for enzymes
      that modify nucleotide sugars, and to components of sugar translocation systems
      that have so far been rarely described in bacteria.

PMID- 11589582
TI  - Establishment of a gene transfer system for Pseudozyma flocculosa, an
      antagonistic fungus of powdery mildew fungi.
AB  - A reliable DNA-mediated transformation system has been developed for Pseudozyma
      flocculosa, a fungus that is antagonistic to powdery-mildew fungi. Plasmids
      harboring various selectable markers under the control of different promoters
      were tested. Molecular analyses demonstrated that successful transformation could
      be achieved using a plasmid that confers resistance to hygromycin B under the
      control of the Ustilago maydis hsp70 promoter and terminator sequences. On
      average, 1-40 (mean = 20) transformants were obtained per 10 microg of linearized
      DNA per 10(8) protoplasts. Southern analysis of the transformants revealed that,
      in each case, the vector had integrated in multiple tandem copies into the genome
      of P. flocculosa, and that integration events were random. Pulsed-field gel
      electrophoresis was employed to separate the genome of P. flocculosa into at
      least 11 chromosomes with sizes ranging from 0.55 Mb to 2.9 Mb. Hybridization
      with the plasmid indicated that integration of vector DNA had occurred in one to
      several chromosomes depending on the transformant examined.

PMID- 11589583
TI  - Simultaneous modelling of metabolic, genetic and product-interaction networks.
AB  - The creation of cell models from annotated genome information, as well as
      additional data from other databases, requires both a format and medium for its
      distribution. Standards are described for the representation of the data in the
      form of Document Type Definitions (DTDs) for XML files. Separate DTDs are
      detailed for genetic, metabolic and gene product-interaction networks, which can
      be used to hold information on individual subsystems, or which may be combined to
      create a whole cell DTD. In the execution of this work, a fifth DTD was also
      created for a metabolite thesaurus, which allows incorporation of metabolite
      synonyms and generic nomenclature data into the models. A gene-regulation
      classification scheme was also created, to facilitate incorporation of gene
      regulatory information in an efficient manner. The work is described with
      particular reference to the metabolic network of Escherichia coli, which contains
      808 individual enzymes. The assignment of confidence levels to these data,
      through the use of Gene Ontology evidence codes, is highlighted. In silico
      investigations may now be performed using the mathematical simulation workbench,
      DBsolve, which incorporates the facility to introduce data directly from XML.

PMID- 11589584
TI  - Engineering virtual cardiac tissue.
AB  - The kinetics of proteins involved in ion transfer, sequestration and binding in
      cardiac cells can be modelled to construct a model of the electrical activity of
      isolated cardiac cells as a system of ordinary differential equations. These cell
      models may be incorporated into tissue models, which, when combined with
      histology and anatomy, form virtual tissues. The effects of changes in specific
      protein expression, or changes in protein kinetics, produced by mutations or
      pharmacological agents, can be simulated using these tissue models and used to
      account for the whole organ effects of changes in specific ion-transport protein
      activity.

PMID- 11589585
TI  - An approach to modelling in immunology.
AB  - Like most other fields in biology, immunology has been revolutionised by the
      techniques of molecular biology and the resulting explosion in available
      experimental data. It is argued that efforts to integrate the data to gain
      insight into how various subsystems in the immune system interact and function
      require mathematical modelling and computer simulation in close collaboration
      with experimentalists. This paper illustrates some of the techniques available
      for modelling immune systems, and highlights the issues that should be borne in
      mind by anyone starting down the modelling path.

PMID- 11589586
TI  - Systems biology: the reincarnation of systems theory applied in biology?
AB  - With the availability of quantitative data on the transcriptome and proteome
      level, there is an increasing interest in formal mathematical models of gene
      expression and regulation. International conferences, research institutes and
      research groups concerned with systems biology have appeared in recent years and
      systems theory, the study of organisation and behaviour per se, is indeed a
      natural conceptual framework for such a task. This is, however, not the first
      time that systems theory has been applied in modelling cellular processes.
      Notably in the 1960s systems theory and biology enjoyed considerable interest
      among eminent scientists, mathematicians and engineers. Why did these early
      attempts vanish from research agendas? Here we shall review the domain of systems
      theory, its application to biology and the lessons that can be learned from the
      work of Robert Rosen. Rosen emerged from the early developments in the 1960s as a
      main critic but also developed a new alternative perspective to living systems, a
      concept that deserves a fresh look in the post-genome era of bioinformatics.

PMID- 11589587
TI  - Computational models of cells and tissues: machines, agents and fungal infection.
AB  - Computational models have been of interest in biology for many years and have
      represented a particular approach to trying to understand biological processes
      and phenomena from a systems point of view. Much of the early work was rather
      abstract and high level and probably seemed to many to be of more philosophical
      than practical value. There have, however, been some advances in the development
      of more realistic models and the current state of computer science research
      provides us with new opportunities through both the emergence of models that can
      model seriously complex systems and also the support that modern software can
      give to the modelling process. This paper describes a few of the early simple
      models and then goes on to look at some new ideas in the area with a particular
      application drawn from the world of mycology. Some general principles relating to
      how new and emerging computational techniques can help to represent and
      understand extremely complex models conclude the paper.

PMID- 11589588
TI  - Can correlated mutations in protein domain families be used for protein design?
AB  - Evidence from diverse studies, such as protein design experiments and analysis of
      the emergence of drug resistance in human immunodeficiency virus 1 (HIV-1),
      indicates that protein function can be diminished or altered by mutations at
      positions distant from the classic 'functional' site. Furthermore, results from
      correlation analysis of the ligand-binding domain of nuclear receptors suggest
      that mutation events at positions distributed throughout a protein domain may be
      involved in functional diversification during the evolution of homologous domain
      families. This review explores potential applications for a protein design
      procedure based on correlated substitutions.

PMID- 11589590
TI  - Software review. Gepasi 3.0.

PMID- 11589589
TI  - Ontologies of developmental anatomy: their current and future roles.
AB  - A central problem in current biology is elucidating the molecular networks that
      drive developmental change and physiological function. Such knowledge is needed
      partly to understand these networks, partly to be able to manipulate them, and
      partly to understand and help treat those human congenital abnormalities that
      arise as a result of mutation. Thus far, bioinformatics technology has been of
      limited use in this enterprise, mainly because its core focus has been on
      sequence technology and data archiving. For bioinformatics to be of use in this
      next tier of investigations, genetic and protein data need to be both archived
      and searchable by tissue since this is the level at which these networks operate.
      The resulting databases in turn require ontologies of developmental anatomy that
      can provide the formal infrastructure for handling gene expression, microarray
      and other tissue-based data. Here, the progress in making such ontologies,
      particularly for the developing mouse, is reported and the uses to which they are
      and will be put, together with the resources and tools currently available for
      investigating molecular networks and the genetic basis of congenital
      abnormalities, are considered.

PMID- 11589591
TI  - Is upper mediastinal lymphadenectomy necessary in squamous carcinoma of the lower
      thoracic oesophagus?
AB  - AIM: We examined the indication of upper mediastinal lymphadenectomy for a
      squamous cell carcinoma of the lower thoracic oesophagus. METHODS: 49 patients
      underwent a curative oesophagectomy with upper mediastinal lymphadenectomy for a
      squamous cell carcinoma of the lower thoracic oesophagus. Node status and
      clinicopathological characteristics of these patients were reviewed
      retrospectively. RESULTS: 16 (94.1%) of 17 patients with superficial tumours had
      no positive node in the upper mediastinum. Nine (29.0%) of 31 patients with
      transmural tumours had positive nodes in the upper mediastinum (P = 0.04). Ten
      (20.4%) of 49 patients had many positive nodes in the upper mediastinum. Of these
      10 patients, 6 patients had 5 or more positive nodes in all. The 5-year survival
      rate for patients with 5 or more positive nodes was 7.7%, which was significantly
      poorer than patients with 4 or fewer positive nodes. CONCLUSIONS: Upper
      mediastinal lymphadenectomy is unnecessary in most of the superficial squamous
      carcinomas of the lower thoracic oesophagus.

PMID- 11589592
TI  - Histogenesis and clinicopathological characteristics of superficially spreading
      carcinoma of the esophagus.
AB  - To explore the possible histogenesis of superficially spreading carcinoma of the
      esophagus, the clinicopathological features of these tumors (n = 44) were
      compared with those of ordinary superficial carcinoma (n = 163). Tumors of a
      heterogeneous histological type and having in situ carcinoma components were
      significantly more common (P < .05), and the number of residual squamous islands
      was significantly greater (P < 0.05) in the former group than the latter.
      Furthermore, the tumor size was not different among in situ, intramucosal, and
      submucosal carcinomas of the former, whereas the tumors became larger according
      to the depth of invasion in the latter group. These results indicate that the
      collision of multiple simultaneously developing superficial tumors is a plausible
      histogenesis of superficially spreading carcinoma of the esophagus.

PMID- 11589593
TI  - Significant prognostic factors in patients with early gastric cancer.
AB  - BACKGROUND: Early gastric cancer is defined as a gastric carcinoma confined to
      the mucosa or submucosa regardless of lymph node status, and it has an excellent
      prognosis with a 5-year survival rate of more than 90%. From 1985 to 1995, we
      encountered 266 cases of early gastric cancer in our hospital. METHODS: A
      retrospective analysis of the 266 cases of early gastric cancer was performed to
      evaluate the prognostic significance of clinicopathological features (age,
      gender, tumor size, tumor location, depth of invasion, lymph node metastasis,
      histological type, lymphatic invasion, vascular invasion, histological growth
      pattern, cancer-stromal relationship and type of operation). RESULTS: The overall
      survival rate of all the patients with early gastric cancer was 95.7%. In
      univariate analysis, the statistical significant prognostic factors were regional
      lymph node metastasis (P = 0.0004), lymphatic invasion (P = 0.0053) and cancer
      stromal relationship (P = 0.0016). Absence of lymph node metastasis and lymphatic
      invasion, and a medullary-type histopathology were associated with improved
      survival. In multivariate analysis, the statistically significant prognostic
      factors were lymph node metastasis and cancer-stromal relationship. CONCLUSIONS:
      Presence of lymph node involvement and a scirrhous type of gastric cancer are
      associated with poor prognosis. Lymph node dissection with gastric resection is
      necessary for patients with early gastric cancer who have a high risk of lymph
      node metastasis. Postoperative chemotherapy is recommended for a scirrhous type
      of early gastric cancer.

PMID- 11589594
TI  - Pathophysiology of pain in chronic pancreatitis: clinical implications from a
      surgical perspective.
AB  - Pain is the main symptom and the major indication for surgery in a large
      proportion of patients with chronic pancreatitis. Since the characters of pain
      (including frequency, severity, duration and cause) differ among the patients
      with chronic pancreatitis, their management remains a difficult and challenging
      problem. Initial treatment is always conservative and may require a
      multidisciplinary approach involving gastroenterologist, anesthesiologist,
      psychologist for chemical addiction (alcohol and/or narcotics), and surgeon. When
      non-operative management fails to achieve pain relief and pain markedly alters
      quality of life, surgery should be considered. A thorough knowledge of the
      pathophysiology of pain offers the theoretical basis for both conservative and
      surgical treatment of chronic pancreatitis. The selection of the surgical
      procedure should be based on the structural changes of the pancreas.

PMID- 11589595
TI  - Which is less invasive--distal pancreatectomy or segmental resection?
AB  - BACKGROUND: For a pancreatic body tumor, distal pancreatectomy (DP) has been a
      standard operation. Segmental resection (SR) of the pancreas has been introduced
      as a less invasive procedure in consideration of preservation of the pancreatic
      functions and postoperative quality of life. Surgical stress and exocrine and
      endocrine functions of the residual pancreas were compared between DP and SR.
      METHODS: Clinical findings including serum levels of C reactive protein (CRP),
      fasting blood sugar, a 120 min value of the 75 g oral glucose tolerance test, and
      N-benzol-L-tyrosyl-p-aminobenzoic acid excretion value (a pancreatic exocrine
      function test) were compared between 47 patients with DP and 10 with SR performed
      for benign pancreatic diseases. RESULTS: Operation time was longer in SR (356
      min) than in DP (272 min; P = 0.0123). Operative blood loss and peri-operative
      blood transfusion were not different between the two groups. Serum levels of CRP
      increased after the operation, reaching the peak on postoperative day 2 or 3, and
      decreased thereafter The peak of serum CRP level was similar between the two
      groups (13.4+/-1.8 mg/dl in SR and 14.8+/-1.1 mg/dl in DP). Postoperative
      hospital stay in 10 patients with SR (65 days) was significantly longer than that
      in 47 with DP (33 days; P = 0.0001). When postoperative complications were
      compared between the two groups, the incidence of pancreatic fistula was
      significantly higher in SR (4/10 [40%]) than in DP (4/46 [9%]; P = 0.0103).
      Abdominal abscess was seen in 30% of SR and in 11% of DP. Postoperative intra
      abdominal hemorrhage was seen only in one patient with SR After DP, glucose
      tolerance deteriorated at short-term in nine of 24 patients examined and at long
      term in two of five patients examined. Only one patient showed improvement of
      glucose intolerance at short-term after the operation. On the other hand, SR
      showed no alteration of the pancreatic endocrine and exocrine functions in eight
      patients examined. CONCLUSIONS: SR is superior to DP from the view-point of
      preservation of the pancreatic functions, although SR has a longer operation
      time, a longer hospital stay and a higher incidence of postoperative
      complications.

PMID- 11589596
TI  - Postoperative intussusception, causal or casual relationships?
AB  - Postoperative intussusception (POI) is a recognised but uncommon condition.
      Primary intussusception has been reported several times from Africa, but there
      are only two reports of postoperative intussusception. A literature review on POI
      was performed by searching the Medline between 1966 and 1998 together with
      relevant references in publications on the subject. Postoperative intussusception
      occurs within a month of an operation. It differs from primary intussusception.
      No specific aetiology has been found. Predisposing factors based on disorder of
      peristalsis have been proposed. At risk are patients with prolonged postoperative
      ileus after prolonged surgery with extensive dissection or after a postoperative
      regimen of radiation and/or chemotherapy. The diagnosis requires a high index of
      suspicion. Contrast radiology is not reliable in the diagnosis. The preferred
      treatment is operative reduction, but resection may be indicated. There are no
      reports of recurrence after surgical treatment. Preventive measures include
      gentle handling and avoidance of drying of intestines at operation. The paucity
      of reports from Africa may mean that the diagnosis is being overlooked.

PMID- 11589597
TI  - Subtotal colectomy for colonic inertia.
AB  - The aim of this study was to assess the outcome of subtotal colectomy for colonic
      inertia (idiopathic slow transit constipation) that was resistant to laxative
      treatment. Twenty-four patients, 19 women and 5 men, with a mean age of 37 years,
      underwent subtotal colectomy with ileorectal or ascendo-rectal anastomosis. All
      patients were available for follow-up, with a mean follow-up of 23 months. Bowel
      frequency was significantly increased from 1.4+/-0.9 times per week to 22.8+/-9
      times per week (average 3.2/day) after surgery (P <0.0001). The incidence of
      abdominal pain was decreased from 75% to 17%, as well as the severity (P
      <0.0001). Two patients who underwent ascendo-rectal anastomosis developed
      recurrent constipation. Two patients used antidiarrheal medication regularly.
      There was no major postoperative morbidity. Five patients were re-admitted due to
      small bowel obstruction; four received successful conservative management, and
      one required enterolysis. 'Excellent' or 'good' outcomes were reported by 21
      patients (87.5%). Subtotal colectomy with ileorectal anastomosis produces
      satisfactory results in the majority of patients with proven colonic inertia.

PMID- 11589598
TI  - Surgical outcomes research--a new paradigm for clinical research?
AB  - OBJECTIVE: To define outcomes research in terms of a paradigm, grouping six
      existing research methodologies. BACKGROUND: Although outcomes research is
      becoming an increasingly popular area in clinical research, an accepted
      definition is difficult to find. The term 'outcomes research' is often used in
      the context of a research methodology. METHODS: Topics in dinical research which
      have been termed 'outcomes research' are discussed including: databases, quality
      of life studies, effectiveness studies, economic evaluations, small-area rate
      variation analysis and volume outcome studies, as well as practice guideline
      development. RESULTS: Outcomes research is not a research methodology in its own
      right, but a paradigm which groups existing methodologies, providing a structured
      approach to evaluating the outcomes which are most important to patients, society
      and those who pay for health care.

PMID- 11589599
TI  - Predictors for morbidity and mortality following non-traumatic splenectomy at the
      University Hospital, Jeddah, Saudi Arabia.
AB  - OBJECTIVE: To determine the pre-operative predictors of morbidity and mortality
      of patients undergoing elective splenectomy for non-trauma indications. METHODS:
      Analysis of 123 patients who underwent splenectomy at King Abdulaziz University
      Hospital, Jeddah, Saudi Arabia between 1986-1996. Data collected included
      patients' demographic data, indication for splenectomy, laboratory data, details
      of operative procedure and postoperative events for morbidity and mortality.
      Statistical analysis was carried out using the Chi-square test. RESULTS: Of the
      patients, 69% were males and 31% females with ages ranging from 13-72 years (mean
      39 years). Portal hypertension constituted 55% of the indications and benign
      hematological conditions 26%. The morbidity rate was 27.6% and the commonest
      complication was chest and wound infection in 6.6% and 5.7%, respectively. Age of
      >50 years, pre- and postoperative haematocrit of <33%, thoraco-abdominal approach
      and operative time of >120 min had P values of < 0.05, <0.002, <0.03 and <0.03,
      respectively for postsplenectomy mortality. CONCLUSIONS: According to this study,
      age of >50 years is a significant predictor for morbidity following splenectomy,
      whereas age >50 years, pre- and postoperative haematocrit of <33%, thoraco
      abdominal approach and operative duration >120 min were significant predictors of
      postsplenectomy mortality.

PMID- 11589600
TI  - Internal herniation of wandering spleen--a rare cause of recurrent abdominal
      pain.
AB  - A rare case of wandering spleen herniating through a defect in transverse
      mesocolon, which was managed electively by splenopexy using polyglycolic acid
      mesh is reported. An enlarged wandering spleen is at constant risk of trauma,
      torsion and infarction. Internal herniation seems to increase the above risks.
      Early recognition and elective splenopexy should be the treatment of choice.

PMID- 11589601
TI  - Devascularization procedure and DSRS: a controlled randomized trial on selected
      haemodynamic portal flow pattern in schistosomal portal hypertension with
      variceal bleeding.
AB  - OBJECTIVES: The use of duplex studies for the portal tree has revolutionized the
      concepts of haemodynamic pathophysiology in the case of portal hypertensive
      bleeders. The identification of possible haemodynamic patterns in schistosomal
      bleeders, and the effects of devascularization procedure and distal lienorenal
      shunts on a selected haemodynamic pattern, are the aim of this work. PATIENTS AND
      METHODS: Patients (219) with schistosomal hepatic fibrosis and history of
      bleeding oesophageal varices were studied. The patency, diameter, velocity and
      flow volume/min in the portal and splenic veins were followed by coloured Duplex.
      Two matched groups (30 patients each) with the most commonly found haemodynamic
      pattern (splenic vein flow exceeding portal vein flow) were operated upon.
      Devascularization procedure was done for the first group (A) and distal
      splenorenal shunt for the second group (B). RESULTS: Coloured duplex assessment
      of portal circulation in schistosomal patients identified four haemodynamic
      patterns. Pattern I (approximately 59%); splenic vein flow exceeds the portal
      vein flow. Pattern II (approximately 28%); portal vein flow exceeds splenic vein
      flow. In both patterns, the portal flow was hepatopedal. Patterns III and IV (8%
      and 5%, respectively) were associated with hepatofugal flow. Splenic vein flow
      exceeds portal vein flow in pattern III and the reverse in pattern IV. Distal
      lienorenal shunts done for patients with haemodynamic pattern I was followed by a
      rebleeding rate of 3.3% while devascularization done for patients with the same
      pattern was followed by a rebleeding rate of 26.6%. Mild encephalopathy was
      detected in 10% of patients with distal lienorenal shunts and responded to
      dietary regulations. CONCLUSIONS: DSRS proved to be ideal for schistosomal
      patients with hepatopedal flow and splenic vein flow exceeding portal vein flow;
      since in addition to eliminating the high splenic flow out of portal circulation,
      it decreased the pressure in the gastroesophageal region. Other patterns with
      their frequencies and the suggested surgical procedures were also presented.

PMID- 11589602
TI  - Descending necrotizing mediastinitis.
AB  - Between 1990-1999, six patients (mean age, 41.5 years) with the diagnosis of
      descending necrotizing mediastinitis were surgically treated at our institution.
      All patients underwent cervical drainage plus an aggressive mediastinal
      debridement and drainage via posterolateral thoracotomy. The outcome was
      favorable in all cases. All patients received initially a high dose of broad
      spectrum antibiotics. In four patients, a tracheostomy was necessary for
      respiratory management. We also review the literature.

PMID- 11589603
TI  - Primary lung epithelioid hemangio-endothelioma with multiple bilateral
      metachronous localizations: case report and review.
AB  - The authors report a case of primary epithelioid (EH) in a 73-year-old female.

PMID- 11589605
TI  - The value of fibrin sealant in thyroid surgery without drainage.
AB  - Fibrin sealant is widely used to achieve complete hemostasis in many fields of
      surgery. A retrospective review of the surgical management of 81 patients with
      thyroid diseases between 1992 and 1998 was undertaken to determine if drainage
      after thyroid surgery could be safely avoided and substituted by fibrin sealing
      before closure of the wound. Complications were few and resulted in one patient
      with hoarseness, four minor oedemas and one case of unexplained fever during 48
      h. The subjective discomfort from the collar incision was unusual and aesthetic
      healing was obtained in most of the cases (93.8%). These results suggest that the
      application of fibrin sealant can be advocated in thyroid surgery as an adjunct
      to a good surgical procedure and perhaps that prophylactic drainage is
      unnecessary.

PMID- 11589604
TI  - Psoas abscess: diagnostic and therapeutic considerations in six patients.
AB  - Psoas abscess (PA) is an infrequent clinical entity and presents diagnostic and
      therapeutic challenges. Six cases are reported concerning diagnostic and
      therapeutic considerations. Clinical diagnosis is difficult because of non
      specific symptoms. The primary psoas abscess has no definite etiology and is
      spread by hematogeneous route from a distant occult site. The PA can also be
      secondary to gastrointestinal pathology through direct infection of adjacent
      structures. The most common causes are Crohn's disease, appendicitis,
      diverticulitis and carcinoma. Routine laboratory evaluation is seldom useful for
      localizing the disease process. Conventional radiological techniques are often
      unhelpful. Modern imaging diagnosis techniques such as ultrasound and
      computerized tomography have allowed for a refinement in both the etiologic
      diagnosis and the treatment by means of CT-guided or ultrasound-guided
      percutaneous drainage of the abscess, thus avoiding surgical drainage in many
      cases. Immediately on diagnosis of PA prompt treatment is necessary. Percutaneous
      drainage should be performed whenever possible and in case of failure, surgical
      drainage should be practiced as well as intestinal resection, whenever indicated.

PMID- 11589606
TI  - The use of the 'TRAM' flap in some oncological problems.
AB  - The present study was conducted to evaluate the use of the transverse rectus
      abdominis myocutaneous (TRAM) flap in immediate autologous soft tissue coverage
      of the large wound defect that results from some oncological problems and would
      be impossible to close by direct primary sutures. The study included patients
      with locally advanced breast cancer (LABC) (n = 24), post-mastectomy local
      recurrence (n = 10), post-mastectomy irradiation ulcer (n = 4), recurrent
      fibrosarcoma of the chest wall (n = 1), and a huge ulcerating malignant melanoma
      of the groin region (n = 1). All patients were female except for the patient with
      melanoma. Their ages ranged between 39-73 years with an average of 56.2 years.
      The lower TRAM flap was used in 24 patients and the middle in only six. Mesh re
      inforcement of the abdominal wall was adopted in 14 patients (35%). The mean
      operating time was 2.5 h and the average postoperative hospital stay was 9.7 days
      (range, 7-12 days). Six patients (15%) had partial flap necrosis which healed
      after debridement and secondary sutures, and eight patients had wound sepsis
      (20%). No patient suffered from abdominal herniation, although four patients
      (10%) had an epigastric bulge postoperatively. During the 48.5 month follow-up
      period (range 36-56 months), three cases of local recurrence and four cases of
      distant metastases were encountered in the patients with LABC. Three of the
      latter died at 7, 11 and 12 months postoperatively. Based on these data, it may
      be concluded that the results of the TRAM flap for immediate coverage of the
      large post-extirpation defect in different oncological problems have been
      encouraging. No flaps were lost, no abdominal herniation was encountered, and
      overall complications were minimal.

PMID- 11589607
TI  - Epidural analgesia attenuates the systemic stress response to upper abdominal
      surgery: a randomized trial.
AB  - The effects of combined general anaesthesia and epidural analgesia in various
      endocrine and metabolic parameters were studied before, during, at the end, and
      72 h after upper abdominal surgery, in an effort to further elucidate the role of
      epidural analgesia in the endocrine and metabolic response. 50 patients were
      randomly assigned into groups A and B, which received general anaesthesia alone
      and combined general anaesthesia and epidural analgesia, respectively. The
      effects of surgical stress in the plasma concentration of ACTH (P <0.001),
      cortisol (P <0.01), aldosterone (P <0.05), FFA (P <0.05) and glucose (P <0.01)
      were significantly less pronounced in the group of patients who received combined
      general anaesthesia and epidural analgesia. However, there were no significant
      differences between the two groups in regard with plasma TSH, T3, T4, glucagon or
      Na+ concentration. These results indicate that the combination of general
      anaesthesia and epidural analgesia attenuate, but does not inhibit, the endocrine
      and metabolic response to upper abdominal surgery.

PMID- 11589608
TI  - Surgical treatment of human echinococcosis.
AB  - Hydatid disease may affect several organs in the human body and thus represents a
      major challenge for the general surgeon. The aim of this study was to analyze the
      multiple clinical presentations of hydatid disease and the surgical options
      according to the involved organ. The medical records of 272 adult patients
      operated on for hydatid disease in our department during the period 1970-1996
      were retrospectively reviewed. The most commonly involved organ was the liver
      (204 patients; 75%), followed by the lung (42 patients; 15.4%) and the spleen (14
      patients; 5.1%). In 12 patients, the cysts were located in uncommon sites: in the
      pancreas (4 patients; 1.5%), the gallbladder (2 patients; 0.74%), the kidney, the
      thyroid gland, the breast, the pericardium, the supraclavicular region and the
      thigh (1 patient in each case; 0.37%). Clinical symptomatology varied according
      to anatomic location and pre-operative diagnosis was accomplished with plain
      abdominal films, ultrasound, computerized tomography and serological tests. The
      surgical procedures performed included simple closure with drainage, unroofing of
      the cyst with omentoplasty (for liver cysts), marsupialization, cyst excision,
      excision of the involved organ or combinations of procedures. Postoperative
      morbidity was mainly due to septic complications (n = 41), postoperative bleeding
      (n = 2), deep vein thrombosis (n = 2) and fistulae (n = 13). Four patients died
      in the early postoperative period (mortality rate, 1.5%) secondary to septic
      complications (n = 3) and pulmonary embolism (n = 1). During long-term follow-up,
      14 patients developed recurrent disease. In conclusion, hydatid disease should be
      included in the differential diagnosis of cystic masses in solid organs or other
      anatomic sites, especially in endemic countries. Since there is not an effective
      medical treatment, surgery still remains the treatment of choice, offering a good
      clinical result and an acceptable recurrence rate.

PMID- 11589610
TI  - Quantification of annexin I in subcellular fractions of human neutrophils reveals
      an exclusive cytosolic localisation.
AB  - Annexin I is an abundant cytosolic protein in human neutrophils. Besides its
      intracellular location, annexin I is found as an extracellular protein and the
      pathway for secretion has been of interest since the protein lacks a signal
      sequence for secretion. It was recently shown that annexin I is stored in the
      secretory gelatinase granules of human neutrophils, suggesting that the protein
      might be released through a granule mobilisation and fusion process resembling
      classical secretion. In this study we have determined the intracellular
      localisation of annexin I in human neutrophils using subcellular fractionation,
      protein separation by SDS-PAGE and immunoblotting, and show that virtually all
      annexin I is localised in the cell cytosol.

PMID- 11589611
TI  - Characterisation of myogenic cell membrane: II. Dynamic changes in membrane
      lipids during the differentiation of mouse C2 myoblast cells.
AB  - Proliferating mouse C2 myoblast cells resist haemagglutinating virus of Japan,
      Sendai virus (HVJ) mediated cell fusion. However, differentiating C2 cells can be
      induced to fuse by HVJ, suggesting that the rigid membrane of C2 cells changes
      during the differentiation. To investigate this phenomenon, changes in membrane
      lipids which affect fluidity were examined. Membrane cholesterol gradually
      decreased with the differentiation of C2 cells. However, spontaneous fusion to
      form myotubes and artificial fusion induced by HVJ were both inhibited when the
      level of cholesterol was prevented from falling in the cell membrane. The
      membranes of differentiating C2 cells contained more unsaturated fatty acids than
      those of proliferating cells. Thus, when differentiating C2 cells were treated
      with stearate (a saturated fatty acid), they failed to form myotubes and were
      insensitive to HVJ-mediated fusion. Whereas, if proliferating C2 cells were given
      linolenate (an unsaturated fatty acid), they became capable of HVJ-induced
      fusion. These results indicate that differentiating C2 cells change their fusion
      sensitivity by decreasing cholesterol, probably at the same time as they increase
      the unsaturated fatty acid content of the cell membrane.

PMID- 11589612
TI  - Microtubule assembly is directly affected by MPP(+)in vitro.
AB  - The microtubular system is emerging as a cell target in neurodegeneration evoked
      by the Parkinsonism-inducing neurotoxin N-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) and its toxic metabolite N-methyl-4-phenylpyridinium
      (MPP(+)). Looking for a direct effect of the neurotoxin on microtubules, we have
      undertaken an in vitro study by using microtubule protein purified from bovine
      brain. We show that MPP(+), but not MPTP, modifies the initial rate and the
      critical concentration of assembly without affecting microtubule ultrastructure.
      These findings strengthen the hypothesis for the role of microtubules in the
      transduction of MPP(+)neurotoxic effect and, probably, in neuronal cell death.

PMID- 11589613
TI  - Detection of submicroscopic magnetite particles using reflectance mode confocal
      laser scanning microscopy.
AB  - Light microscopy and transmission electron microscopy work at such different
      scales that some components of cells may be too small to detect using light
      microscopy but too dispersed among cells within tissues to be discovered using
      electron microscopy. We have used reflectance mode confocal laser scanning
      microscopy to detect single-domain magnetite crystals in both live and resin
      embedded preparations of magnetotactic bacteria. We show that reflections from
      bacterial cells are uniquely associated with the magnetite, which underpins the
      magnetotactic response of the bacteria. En bloc viewing shows that relatively
      large volumes of material can be searched with sufficient resolution to enable
      detection of submicroscopic particles. The techniques reported here may be of
      interest to others wishing to detect submicroscopic objects dispersed in large
      volumes of tissue.

PMID- 11589615
TI  - cGMP-regulated store-operated calcium entry in human hepatoma cells.
AB  - This study aimed to investigate cGMP-regulated store-operated Ca(2+)entry in
      human 7721 hepatoma cells. [Ca(2+)](i)was measured using Fura2/AM. After
      incubation of the cells with 4 microm thapsigargin, Ca(2+)entry was evoked by
      application of 1 mMm Ca(2+)to extracellular solution and was blocked by 3 m m
      Ni(2+), indicating the presence of store-operated Ca(2+)entry in human 7721
      hepatoma cell line. Application of 8-Br-cGMP reduced the [Ca(2+)](i)in hepatoma
      7721 cells by 80%. These data demonstrated for the first time that store-operated
      Ca(2+)entry pathway is present in human hepatoma cells, which is regulated by
      cGMP.

PMID- 11589616
TI  - Carcinogenesis or tumourigenicity testing of animal cell lines for vaccine
      preparation by colony formation on soft agar and by agglutination under plant
      lectins.
AB  - The carcinogenic or tumourigenic testing of seven animal kidney cell lines (F-81,
      CRFK, MDCK, Vero, Vero-2 cell line, MA-104 and BHK-21) established in China, were
      carried out in more than 700 nude mice for colony formation in soft agar and for
      agglutination under different density of plant lectins. Tests showed that there
      were correlation between cell line chromosome number variations and anchorage
      independence in soft agar, agglutinability under lectins and tumour-forming
      ability in nude mice. Since testing in vitro was more economical, simpler and
      faster and thus thought to be more reliable, we recommend measuring
      agglutinability, followed by anchorage independence or analysis of karyotype as
      the initial means for monitoring tumourigenicity of animal cell lines in nude
      mice.

PMID- 11589617
TI  - Studies of apoptosis of malignant lymphoma cells induced by arsenic trioxide.
AB  - The present study investigated the effect of As(2)O(3)on malignant lymphoma
      cells. Cell apoptosis was detected by cell staining and TdT-mediated dUTP Nick
      end Labelling (TUNEL). Cellular DNA and protein expression content were
      determined by immunohistochemistry and flow cytometry. It was found that 0.5-2.0
      microm /l As(2)O(3)could inhibit cell growth, including Raji cells and lymphoma
      cells from patients, and induce apoptosis, such as condensed chromatin and
      nuclear fragmentation with intact cell membrane, i.e. apoptotic body. It was also
      found that the cells of the sub-G(1)phase increased significantly and bcl-2 gene
      expression was greatly downregulated. However, this effect was not observed for
      Jurkat cells under the same conditions. We concluded that As(2)O(3)at a range of
      0.5-2.0 microm /l can inhibit the growth and induce apoptosis in malignant
      lymphoma cells, which may have therapeutic potential.

PMID- 11589618
TI  - Quantification of apoptotic DNA fragmentation in a transformed uterine epithelial
      cell line, HRE-H9, using capillary electrophoresis with laser-induced
      fluorescence detector (CE-LIF).
AB  - Apoptotic cell death of uterine epithelial cells is thought to play an important
      role in the onset of menstruation and the successful implantation of an embryo
      during early pregnancy. Abnormal apoptosis in these cells can result in
      dysmenorrhoea and infertility. In addition, decreased rate of epithelial
      apoptosis likely contributes to endometriosis. A key step in the onset of
      apoptosis in these cells is cleavage of the genomic DNA between nucleosomes,
      resulting in polynucleosomal-sized fragments of DNA. The conventional technique
      for assessing apoptotic DNA fragmentation uses agarose (slab) gel electrophoresis
      (i.e. DNA laddering). However, recent technological advances in the use of
      capillary electrophoresis (CE), particularly the introduction of the laser
      induced fluorescence detector (LIF), has made it possible to perform DNA
      laddering with improved automation and much greater sensitivity. In the present
      study, we have further developed the CE-LIF technique by using a DNA standard
      curve to quantify accurately the amount of DNA in the apoptotic DNA fragments and
      have applied this new quantitative technique to study apoptosis in a transformed
      uterine epithelial cell line, the HRE-H9 cells. Apoptosis was induced in the HRE
      H9 cells by serum deprivation for 5, 7 and 24 h, resulting in increased DNA
      fragmentation of 2.2-, 3.1- and 6.2-fold, respectively, above the 0 h or plus
      serum controls. This ultrasensitive CE-LIF technique provides a novel method for
      accurately measuring the actions of pro- or anti-apoptotic agents or conditions
      on uterine epithelial cell lines.

PMID- 11589619
TI  - Application of cell engineering technology to the tumour immunotherapeutic drug:
      a review.
AB  - The concept of cell engineering is frequently mentioned in recent years. It's a
      comprehensive technology which is very powerful and useful. By using it,
      scientists can produce many kinds of proteins and other biological moleculars in
      large scale that are in great demand for the human being. Among these products,
      most can be used for tumor immunotherapy and have been confirmed to be very
      effective in tumour control or subsidiary treatment. Of them, most common and
      useful drugs include three sorts; tumour vaccines, cell factors and monoclonal
      antibodies. The paper will discuss in detail related drugs application advances
      in tumour immunotherapy.

PMID- 11589620
TI  - Suppression of ATP-induced Cl(-)secretion by enhanced expression of epithelial
      Na(+)channels in mouse endometrial epithelium.
AB  - We have studied the effect of enhanced expression of epithelial Na(+)channels
      (ENaC) on the ATP-induced Cl(-)secretion in the mouse epithelium using short
      circuit current (I(SC)) and RT-PCR techniques. The amiloride sensitivity of basal
      current (I(b)) across the cultured endometrial epithelia was found to vary with
      the magnitude of the I(b), the higher the I(b)the greater its sensitivity to
      amiloride, indicating possible elevation of ENaC. However, the magnitude of ATP
      induced I(SC), previously demonstrated to be mediated by Ca(2+)-activated
      chloride channel (CaCC), decreased as the amiloride sensitivity of the
      I(b)increased, suggesting a possible inhibitory effect of elevated expression of
      ENaC on ATP-mediated chloride secretion. The Matrigel treatment for culturing the
      endometrial epithelia affected the amiloride sensitivity of the I(b)as well as
      the ATP-induced I(SC)reversedly. Competitive RT-PCR demonstrated that the
      expression of both ENaC gamma subunits and CaCC was enhanced in Matrigel-treated
      cultures. However, the observed reduction in the ATP-induced or CaCC-mediated
      I(SC)could not be explained by the CaCC expression pattern. These data suggest
      that inhibition of CaCC function is due to enhanced ENaC expression. Therefore,
      in addition to interacting with CFTR, ENaC also appears to interact with CaCC in
      the mouse endometrial epithelium. Physiologically the present findings indicate
      that enhanced expression of ENaC leads to suppression of other Cl(-)channels,
      such as CFTR and CaCC, thereby preconditioning the endometrium in favour of
      overall salt and water absorption as observed during embryo implantation.

PMID- 11589621
TI  - Effect of phenol red and steroid hormones on cystic fibrosis transmembrane
      conductance regulator in mouse endometrial epithelial cells.
AB  - Previous studies have demonstrated that cystic fibrosis transmembrane conductance
      regulator (CFTR), a cAMP-mediated Cl(-)channel found in most epithelia including
      reproductive tract, could be regulated by various culture conditions. The present
      study further investigated the effect of phenol red, a pH indicator widely used
      in growth medium, and steroid hormones, present in the supplement fetal bovine
      serum (FBS), on primary cultured endometrial epithelial cells by monitoring ion
      channel activities using the short-circuit current technique. When compared to
      the results obtained with normal medium supplemented with regular FBS, the
      forskolin-stimulated I(SC), presumably mediated by CFTR, obtained in phenol red
      free medium was significantly reduced, from 16.95+/-1.53 microA/cm(2)(control) to
      9.72+/-0.89 microA/cm(2)(medium without phenol red, P< 0.05). The forskolin
      activated I(SC)was further attenuated to 5.29+/-0.46 microA/cm(2)in the phenol
      red-free medium when supplemented with charcoal/ dextran-treated FBS where
      steroid hormones were removed. Our data suggest that phenol red and steroid
      hormones present in culture medium and FBS supplement, respectively, may somehow
      upregulate CFTR expression in vitro. Our study demonstrates the need for
      carefully choosing the culture media and supplements due to the effect of steroid
      hormones.

PMID- 11589622
TI  - Effect of human oviductal epithelial cell cultural medium on cryopreserved human
      sperm survival.
AB  - The human oviduct is known as a functional site for gamete transportation,
      retention, fertilization and zygote development. Previous studies have shown that
      human oviductal epithelial cell cultural medium (OECCM) has a positive effect on
      prolongation of sperm motility for some cryopreserved human sperm without
      cryodamage. However, for most cryopreserved sperm, OECCM could not improve their
      survival prolongation. In this study, we assessed the influence of human OECCM on
      the motility longevity of cryopreserved human sperm with an in vitro incubation
      method.

PMID- 11589623
TI  - Effects of leukaemia inhibitory factor on endometrial receptivity and its
      hormonal regulation in rabbits.
AB  - The effects of hormones on production of leukaemia inhibitory factor (LIF) and
      the uterine receptivity in rabbits were studied. In ovariectomised rabbits, LIF
      protein was not detected in control but upregulated by progesterone alone.
      Oestrogen had a slightly negative effect when the rabbits were treated with both
      oestrogen and progesterone. Mifepristone (Mi) inhibited the progesterone
      stimulated production of LIF in rabbit uterus. The transfer of embryos to LIF
      treated recipients significantly increased pregnancy rate (70%) and implantation
      rate (27%) as compared with control (pregnancy rate=40% and implantation
      rate=17%). The transfer of embryos to LIF and mifepristone-treated recipients
      significantly decreased pregnancy rate (30%) and implantation rate (9%). The
      results indicated that LIF protein had a beneficial effect on uterine receptivity
      and mifepristone prevented this effect.

PMID- 11589624
TI  - Upregulation of cystic fibrosis transmembrane conductance regulator expression by
      oestrogen and Bak Foong Pill in mouse uteri.
AB  - Although cystic fibrosis transmembrane conductance regulator (CFTR) has been
      shown to be expressed in the female reproductive tract, its functional role in
      the uterus is not fully understood. The present study investigated a possible
      physiological role of CFTR by comparing the effects of 17beta-oestradiol and Bak
      Foong Pill (BFP), an over-the-counter Chinese medicine used for centuries for the
      treatment of various gynaecological disorders, on uterus size and the expression
      of CFTR in the uterus of ovariectomised mice using RT-PCR. Treatment of
      ovariectomised mice with 17beta-oestradiol (0.2 mg/kg, p.o.) for 12 days caused a
      significant increase in uterine wet weight compared to vehicle. However,
      treatment with BFP (3 g/kg, p.o.) for the same period failed to increase uterine
      wet weight, indicating a lack of direct oestrogen-like activity of BFP. Analysis
      of CFTR mRNA expression in the harvested uteri using RT-PCR showed that both
      17beta-oestradiol and BFP induced an increase in CFTR mRNA expression in mouse
      uteri compared to levels observed in vehicle-treated animals. These results
      suggest that CFTR can be upregulated by oestrogen and BFP, however, the effect
      exerted by BFP does not seem to be mediated by direct oestrogen-like activity.
      Regulation of CFTR expression by both oestrogen and gynaecological medication BFP
      indicates an important role of CFTR in reproductive functions.

PMID- 11589625
TI  - Insulin-like growth factor-I affects amino compounds in the fluids of the chicken
      embryo.
AB  - The concentration differences of more than 40 amino acids and related compounds
      in the amniotic fluid, allantoic fluid, and plasma of the chicken embryo are
      maintained by specific barriers. Since the amniotic and allantoic membranes are
      not innervated, we proposed that these barriers are controlled by hormones.
      Specific effects of insulin and prolactin on the amino compounds in the three
      fluids confirmed this hypothesis and raised the question of the possible role of
      growth factors. Application of insulin-like growth factor-I (IGF-I) to the
      chorioallantoic membrane of day 13 chicken embryos caused the following
      concentration changes in 41 amino compounds measured 1 and 2 h later: (1) in the
      amniotic fluid, an increase of 40 compounds, regardless of the presence or
      absence of a concomitant stress effect on these compounds; only NH3 was not
      affected; (2) in the allantoic fluid, a decrease of reduced glutathione (GSH) and
      anserine, and an increase of NH3; (3) in the plasma, a decrease of 24 compounds.
      Within the same time frame, stress caused in the amniotic fluid a drop of the
      concentration of 29, and an increase of 5, amino compounds; IGF-I reversed the
      stress effect on all 29 compounds the concentrations of which had dropped and
      enhanced the stress-induced increase of the other 5 compounds. In the allantoic
      fluid, stress induced an increase of GSH; IGF-I reversed this effect. In the
      plasma, stress caused an increase of 9 compounds; IGF-I counteracted the increase
      in 7 cases. These findings indicate new and unexpected roles of IGF-I in the
      prenatal regulation of amino compounds.

PMID- 11589626
TI  - The turkey transcription factor Pit-1/GHF-1 can activate the turkey prolactin and
      growth hormone gene promoters in vitro but is not detectable in lactotrophs in
      vivo.
AB  - The transcription factor Pit-1/GHF-1 plays an important role in regulating the
      prolactin (Prl) and growth hormone (GH) genes in mammals. In this study, the role
      that Pit-1 plays in regulating the prolactin and growth hormone genes in avian
      species was examined by cotransfection assays and immunofluorescence staining of
      pituitary sections. In cotransfection assays, turkey Pit-1 activated the turkey
      Prl, turkey GH, and rat Prl promoters 3.8-, 3.7-, and 12.5-fold, respectively.
      This activation was comparable to rat Pit-1 activation of these same promoters. A
      point mutation in the turkey Pit-1 cDNA, which changed leu-219 to ser-219,
      resulted in a 2-, 2-, and 10-fold reduction in the activation of the turkey Prl,
      turkey GH, and rat Prl promoters, respectively. Unexpectedly, coexpression of
      tPit-1 (leu-219) and tPit-1(ser-219) activated turkey Prl and rat Prl promoters
      9.4- and 35.9-fold, respectively, but had no effect on the turkey GH promoter.
      Dual-label immunofluorescence analysis of turkey pituitary sections revealed that
      Pit-1 was not detectable in prolactin-staining cells but was detectable in GH
      staining cells. Taken together, these data indicate that in the domestic turkey,
      Pit-1 can activate the turkey Prl promoter in vitro, but does not appear to play
      a role in regulating Prl gene expression in vivo. Pit-1, however, still likely
      plays a role in regulating GH gene expression.

PMID- 11589627
TI  - Development of a retinoic acid receptor-binding assay with rainbow trout tissue:
      characterization of retinoic acid binding, receptor tissue distribution, and
      developmental changes.
AB  - Retinoic acid (RA) regulates the transcription of various genes required for
      several essential functions in vertebrates through binding to two classes of
      nuclear receptors, the retinoic acid receptors (RAR) and retinoid X receptors
      (RXR). We investigated nuclear RA binding in tissues from rainbow trout using the
      radiolabeled all-trans and 9-cis isomers of RA. Specific binding (indicative of
      receptor binding) of both all-trans- and 9-cis-RA was found in all tissues
      tested, including the adult trout ovary, testis, gill, liver, kidney, blood,
      white muscle, and heart. The kinetics and absolute amount of RA binding were
      dependent on both the tissue and the isomer of RA used. All-trans-RA bound with
      high affinity (K(d) approximately 1.0-3.9 nM), and low capacity (B(max)
      approximately 75-484 fmol RA/mg protein), while 9-cis-RA bound with lower
      affinity (K(d) approximately 7-56 nM), but with a greater capacity (B(max)
      approximately 214-1076 fmol RA/mg protein). The B(max) results were used to
      estimate RAR and RXR levels and revealed that the gill possesses primarily RARs
      while the liver possesses primarily RXRs. The RAR-specific competitor TTNPB was
      able to effectively displace all-trans-[3H]RA in most tissues, and the RXR
      specific competitor AGN 194204 was able to effectively displace 9-cis-[3H]RA.
      However, TTNPB and AGN 194204 could not displace all of the RA in the kidney and
      testis, suggesting the existence of another nuclear RA binding protein. Binding
      of all-trans- and 9-cis-RA was also found in developing trout embryos and fry.
      Kinetic analysis revealed that RAR levels predominated at the eyed-embryo stage,
      but decreased 87% by the swim-up fry stage, while RXR levels remained relatively
      constant over the same time period. These findings suggest that RA and its
      receptors may play a key role in early trout development. This study has provided
      a simple and rapid radioligand binding assay that can identify RAR and RXRs in
      trout tissues.

PMID- 11589628
TI  - Reproductive endocrinology of a free-living, opportunistically breeding passerine
      (white-winged crossbill, Loxia leucoptera).
AB  - The aim of the study was to investigate, in a free-living opportunistic breeder,
      the White-winged Crossbill (Loxia leucoptera), the degree to which annual changes
      in photoperiod and differences in the timing of breeding in different years
      correlate with the secretion of reproductive hormones. Seasonal changes in
      concentrations of luteinizing hormone (LH) and prolactin were compared in White
      winged Crossbills in interior Alaska (64 degrees 50'N, 147 degrees 50'W) in
      plasma samples taken in May-December 1994 and July 1998-August 1999. The birds
      were in breeding condition in May-July 1994 and in February-April 1999.
      Additional observations were made on plasma testosterone (T) in males in
      1998/1999. In 1998, in adult males, plasma LH and T were low in September-October
      (LH: <0.4 ng/ml; T: undetectable) and increased significantly in November (LH:
      3.65 +/- 2.20 ng/ml) and December (T: 0.69 +/- 0.88 ng/ml). Thereafter, plasma T
      increased to 2.35 +/- 2.03 ng/ml in March/April and returned to basal levels by
      June/July. In 1998/1999, in females, plasma LH did not change seasonally. In
      males in 1994, plasma LH was higher in June (2.15 +/- 1.22 ng/ml) and July (2.86
      +/- 0.69 ng/ml) than in the same period in 1999 (June: 1.20 +/- 1.82 ng/ml; July:
      1.37 +/- 1.03 ng/ml), which is consistent with the later breeding season in 1994.
      In 1994 and 1998/1999 in both sexes, concentrations of plasma prolactin were
      elevated when day lengths exceeded about 12 h, being high during late spring to
      early fall (males: 40-130 ng/ml; females: 40-140 ng/ml) and low during winter
      (<15 ng/ml in both sexes). In 1994 and 1998, molt occurred during the fall, at a
      time when breeding did not occur, although conifer seeds were sufficiently
      abundant to support a large bird population. These data are consistent with the
      view that White-winged Crossbills have the potential to breed at all times of the
      year except when molting in the fall. It is likely that a photoinduced increase
      in prolactin secretion is a factor that induces molt. Crossbills may not breed
      when they are molting because of increased metabolic demands for feather
      formation and for the maintenance of basal metabolism at a time of year when
      ambient temperatures fall well below 0 degrees. Alternatively or in addition, the
      birds may become reproductively photorefractory.

PMID- 11589629
TI  - The physiological effects of 3,5',3'-triiodo-L-thyronine alone or combined with
      cortisol on cultured pavement cell epithelia from freshwater rainbow trout gills.
AB  - The effects of 3,5',3'-triiodo-L-thyronine (T3; 10 or 100 ng ml(-1)), alone or
      combined with cortisol (500 ng ml(-1)), on the physiological properties of
      cultured pavement cell epithelia from freshwater rainbow trout gills were
      assessed. T3 had dose-dependent effects on electrophysiological, biochemical, and
      ion transporting properties of cultured epithelia in both the absence and the
      presence of cortisol. These included reduced transepithelial resistance (TER),
      increased net Na(+) and Cl(-) movement (basolateral to apical) under asymmetrical
      culture conditions (freshwater apical/L15 media basolateral), and elevated Na(+)
      K(+)-ATPase activity. However, paracellular permeability was elevated only in
      high-dose T3-treated preparations. In T3 + cortisol-treated epithelia, similar T3
      induced alterations in TER, net Na(+) and Cl(-) movement, and paracellular
      permeability were observed, whereas the activity of Na(+)-K(+)-ATPase was further
      elevated. Under symmetrical culture conditions (L15 medium apical/L15 medium
      basolateral), T3 had no effect on transepithelial Na(+) and Cl(-) transport,
      which was passive. However, T3 + cortisol treatment resulted in active Na(+)
      extrusion (basolateral to apical). Under asymmetrical conditions, hormone
      treatment did not change the pattern of ion movement (active Na(+) extrusion,
      active Cl(-) uptake). These experiments demonstrate that cultured pavement cell
      epithelia from freshwater rainbow trout are T3-responsive and provide evidence
      for the direct action of T3 and the interaction of T3 and cortisol on the
      physiology of this preparation.

PMID- 11589630
TI  - Transfer of tilapia (Oreochromis niloticus) to a hyperosmotic environment is
      associated with sustained expression of prolactin receptor in intestine, gill,
      and kidney.
AB  - Expression of the tilapia prolactin receptor (tiPRL-R) has been characterized in
      the intestine of Oreochromis niloticus and the levels of both tiPRL-R transcripts
      and tiPRL binding sites have been further analyzed in this organ, as well as in
      gill and kidney, during adaptation of tilapia to a hyperosmotic environment. A
      single high-affinity binding site for tilapia PRL-I (tiPRL-I) was determined in
      full-length intestine by Scatchard analysis. A heterogeneous distribution of
      tiPRL-R was detected in this organ, with the posterior part always displaying a
      higher expression of both tiPRL-R transcript and tiPRL binding sites than the
      anterior and medial parts. Transfer of tilapia to brackish water (BW) led to an
      apparent increase in the specific binding of tiPRLs in intestine and gill even
      for long-term-adapted fish, whereas the high level of kidney tiPRL binding sites
      measured in control fish reared in fresh water was still detected in BW-adapted
      tilapia. There was no overall significant modification of tiPRL-R transcript
      levels in any organ during short-term or long-term adaptation, although a limited
      decrease occurred in the gill of BW-adapted fish, as shown earlier. Therefore, in
      O. niloticus adapted to BW, high and sustained levels of tiPRL-R were observed in
      the three major osmoregulatory organs, gill, kidney, and intestine.

PMID- 11589631
TI  - The effect of low temperature and fasting during the winter on metabolic stores
      and endocrine physiology (insulin, insulin-like growth factor-I, and thyroxine)
      of coho salmon, Oncorhynchus kisutch.
AB  - The objective of this study was to examine the effect of winter feeding and
      fasting at both high (10 degrees ) and low (2.5 degrees ) temperatures on growth,
      metabolic stores, and endocrinology of coho salmon. Treatments were as follows:
      warm-fed, warm-not fed, cold-fed, and cold-not fed during the winter (January
      February). The following parameters were measured: length, weight, whole body
      lipid, liver glycogen, hepatosomatic index, and plasma levels of insulin, insulin
      like growth factor-I (IGF-I), and thyroxine (T4). Warm-fed fish grew continuously
      throughout the experiment from 21.5 +/- 0.3 to 43.4 +/- 1.4 g and were larger
      than fish in the other treatments. Fish in all other treatments grew from 21.5 +/
      0.3 to approximately 32 g and showed depressed growth during January and
      February. During the winter, liver glycogen, hepatosomatic index, plasma insulin,
      and IGF-I were highly influenced by manipulations in rearing conditions, whereas
      whole body lipid and plasma T4 were less affected. Plasma insulin levels
      fluctuated dramatically (from 2 to 7 ng/ml) in the two cold-acclimated groups
      shortly after the change in temperature. In general, the plasma insulin levels of
      the warm-fed fish were the highest (8-9 ng/ml), those of the warm-not fed fish
      were the lowest (2-5 ng/ml), and those of the two cold-acclimated groups were
      more variable but intermediate. In contrast, plasma IGF-I levels showed a decline
      with temperature decrease (from 9 to 5 ng/ml) and more gradual changes than
      insulin with the change in feeding. The highest plasma IGF-I levels were found in
      the warm-fed fish (10-15 ng/ml), the lowest levels were in the cold-not fed fish
      (4-5 ng/ml), and those of the warm-not fed and cold-fed fish were intermediate.
      During the treatment period the T4 levels were relatively unaffected by
      manipulations in feeding and temperature compared with either insulin or IGF-I.
      These data suggest that the insulin, IGF-I, and thyroid axes are differentially
      regulated under changing seasonal and/or environmental conditions in yearling
      salmon.

PMID- 11589632
TI  - Long-term unpredictable foraging conditions and physiological stress response in
      mountain chickadees (Poecile gambeli).
AB  - Birds respond to short-term deterioration in foraging conditions by increasing
      their plasma level of corticosterone but the physiological effects of long-term
      deterioration in food supplies are not well known. In resident passerine birds
      that winter in temperate climates, such as the mountain chickadee (Poecile
      gambeli), the food supply may be limited and unpredictable over long periods of
      time. Whether the long-term limited and unpredictable food supply has an effect
      on (a) baseline levels of corticosterone and (b) the adrenocortical stress
      response to a standardized acute stress of handling and restraint in mountain
      chickadees was assessed. For a period of 94 days, one group of chickadees was
      maintained on limited and unpredictable food (food-restricted) and the other
      group was maintained on an ad libitum food supply. The food-restricted birds had
      significantly higher baseline levels of corticosterone than those maintained on
      ad libitum food. All birds responded to the acute stressor by an increasing
      secretion of corticosterone but there were no differences between the treatment
      groups in their stress response. There was a significant effect of sex on the
      stress response, with females reaching higher levels of corticosterone and
      responding at a faster rate than males. These results suggest that permanent
      resident birds wintering in harsh environments may have elevated levels of
      corticosterone on a long-term basis. Whereas other factors, such as day length
      and ambient temperature, may contribute to energetic hardship during the winter,
      the results showed that limited and unpredictable food alone can trigger
      significant changes in baseline levels of plasma corticosterone. The potential
      costs and benefits of long-term increased corticosterone levels in resident food
      caching birds are discussed.

PMID- 11589633
TI  - Porcine growth hormone and LongR(3)IGF-I can improve recovery from surgery
      induced weight loss in guinea pigs.
AB  - In the present study, porcine growth hormone (pGH) and LongR(3)IGF-I (LR(3)IGF
      I), a potent analogue of IGF-I, were infused continuously into 430-g guinea pigs
      for 7 days, either alone or in combination, to examine whether pGH can counteract
      the reduction in circulating IGF-I concentrations induced by LR(3)IGF-I
      administration. The pGH and LR(3)IGF-I were infused at rates of 400 microg/day
      (0.93 mg/kg/day) and 120 microg/day (0.28 mg/kg/day), respectively, by
      miniosmotic pumps. The same doses were infused in the combination treatment.
      During the first day of treatment, animals lost between 2 and 3% of body weight.
      Cumulative body weight gains as a percentage of initial body weight were
      significantly (P < 0.001) increased relative to vehicle-treated controls by the
      LR(3)IGF-I, pGH, and combination treatments when effects were analyzed across the
      whole 7-day treatment period. The increased weight gains relative to controls
      were largely made on day 2, but these gains were not associated with increased
      water or feed intakes, indicating that pGH and LR(3)IGF-I improved feed
      conversion efficiency. LR(3)IGF-I alone or in combination with pGH significantly
      increased the fractional weight of kidneys at the end of the 7-day treatment
      period, whereas LR(3)IGF-I alone increased the fractional weight of spleens.
      Concentrations of IGF-I in serum collected after 7 days of treatment were
      decreased by LR(3)IGF-I, but this decrease was not ameliorated by coinfusion with
      pGH. GH alone did not have any effects on IGF-I concentration. This study
      suggests that pGH does not have a strong influence on circulating IGF-I
      concentrations in the guinea pig. We have also demonstrated that pGH and LR(3)IGF
      I are capable of enhancing the recovery of body weight lost in response to
      surgery in the guinea pig.

PMID- 11589634
TI  - Effect of capture and season on fecal glucocorticoid levels in deer mice
      (Peromyscus maniculatus) and red-backed voles (Clethrionomys gapperi).
AB  - The effect of confinement and season on fecal glucocorticoid (GC) levels in deer
      mice (Peromyscus maniculatus) and red-backed voles (Clethrionomys gapperi) was
      determined. Deer mice confined in a Sherman trap more than 4 h had fecal GC
      levels that were significantly higher than those in individuals that remained in
      a trap 4 h or less. However, this treatment may not be stressful for red-backed
      voles as neither plasma nor fecal GC levels were significantly elevated after 12
      h of confinement. In addition, a clear temporal pattern in the secretion of fecal
      GCs was observed between mid June and early November in both species.

PMID- 11589635
TI  - Variable timing of reproduction in unpredictable environments: adaption of flood
      plain plants.
AB  - We study the evolutionarily stable reproductive timing of annual plants that face
      unpredictable environmental disturbances. Plants living in a riverbed often
      experience a disturbance before they reproduce, suffering major fitness loss.
      Plants reproducing prior to the flood season are free from the risk of lost
      reproduction, but a small flowering plant can produce only a few numbers of
      seeds. If the date of disturbance is unpredictable, a mixed strategy of
      reproductive timing may evolve in which individuals of the same genotype have
      different reproductive dates. We calculate the evolutionarily stable phenotype
      distribution analytically. Depending on parameters, the ESS distribution is
      either (1) a timid strategy-the plant reproduces when small, prior to the major
      disturbance season; (2) a bold strategy-the plant reproduces only when it is
      fully grown; (3) a mixture of early and late reproduction; or (4) dates of
      reproduction spread over a wide interval. We also examine the effects of
      developmental and environmental noises that make realized flowering dates deviate
      from that programmed by the genotype, which follows the ESS distribution. In the
      presence of noise, the ESS distribution of programmed timing of reproduction is
      discrete.

PMID- 11589636
TI  - Cumulant dynamics of a population under multiplicative selection, mutation, and
      drift.
AB  - We revisit the classical population genetics model of a population evolving under
      multiplicative selection, mutation, and drift. The number of beneficial alleles
      in a multilocus system can be considered a trait under exponential selection.
      Equations of motion are derived for the cumulants of the trait distribution in
      the diffusion limit and under the assumption of linkage equilibrium. Because of
      the additive nature of cumulants, this reduces to the problem of determining
      equations of motion for the expected allele distribution cumulants at each locus.
      The cumulant equations form an infinite dimensional linear system and in an
      authored appendix Adam Prugel-Bennett provides a closed form expression for these
      equations. We derive approximate solutions which are shown to describe the
      dynamics well for a broad range of parameters. In particular, we introduce two
      approximate analytical solutions: (1) Perturbation theory is used to solve the
      dynamics for weak selection and arbitrary mutation rate. The resulting expansion
      for the system's eigenvalues reduces to the known diffusion theory results for
      the limiting cases with either mutation or selection absent. (2) For low mutation
      rates we observe a separation of time-scales between the slowest mode and the
      rest which allows us to develop an approximate analytical solution for the
      dominant slow mode. The solution is consistent with the perturbation theory
      result and provides a good approximation for much stronger selection intensities.

PMID- 11589637
TI  - Autoparasitism, interference, and parasitoid-pest population dynamics.
AB  - Autoparasitoids ("heteronomous hyperparasitoids") are parasitoids that lay female
      eggs on homopteran hosts and male eggs on juvenile parasitoids of either the same
      species or another species. Males develop as hyperparasitoids and eventually kill
      the juvenile parasitoid. We present a series of stage-structured models that
      investigate the effects of autoparasitism on population dynamics. Autoparasitism
      causes density-dependent mortality on juvenile parasitoids and therefore has a
      stabilizing effect. This also leads to an increase in host population abundance.
      In most cases an autoparasitoid leads to higher host equilibrium densities than a
      comparable primary parasitoid (except when the primary parasitoid is
      arrhenotokous (sexual) and the autoparasitoid has a low preference for attacking
      parasitized hosts or can attack the parasitized host for only a small portion of
      its development). When male autoparasitoids are followed explicitly in the
      models, mate limitation reduces the stabilizing effect of autoparasitism and
      leads to a further increase in host abundance. Coexistence of an autoparasitoid
      with a nonprimary parasitoid or second autoparasitoid is possible when the level
      of conspecific autoparasitism is greater than the level of heterospecific
      autoparasitism. When an autoparasitoid coexists with a primary parasitoid, the
      resulting host density is always greater than that with only the primary
      parasitoid. Therefore, autoparasitoids have the potential to disrupt control
      achieved by primary parasitoids. When two autoparasitoids coexist, the resulting
      host density is always lower than that attained by either autoparasitoid alone.
      The effects of autoparasitism are compared with those of other forms of
      interference competition.

PMID- 11589639
TI  - Autonomous practice or autonomous ignorance?

PMID- 11589638
TI  - Realistic distributions of infectious periods in epidemic models: changing
      patterns of persistence and dynamics.
AB  - Most mathematical models used to study the epidemiology of childhood viral
      diseases, such as measles, describe the period of infectiousness by an
      exponential distribution. The effects of including more realistic descriptions of
      the infectious period within SIR (susceptible/infectious/recovered) models are
      studied. Less dispersed distributions are seen to have two important
      epidemiological consequences. First, less stable behaviour is seen within the
      model: incidence patterns become more complex. Second, disease persistence is
      diminished: in models with a finite population, the minimum population size
      needed to allow disease persistence increases. The assumption made concerning the
      infectious period distribution is of a kind routinely made in the formulation of
      mathematical models in population biology. Since it has a major effect on the
      central issues of population persistence and dynamics, the results of this study
      have broad implications for mathematical modellers of a wide range of biological
      systems.

PMID- 11589640
TI  - Evidence-based guidelines: application to clinical practice.

PMID- 11589641
TI  - Philadelphia Panel evidence-based clinical practice guidelines on selected
      rehabilitation interventions: overview and methodology.
AB  - INTRODUCTION: A structured and rigorous methodology was developed for the
      formulation of evidence-based clinical practice guidelines (EBCPGs), then was
      used to develop EBCPGs for selected rehabilitation interventions for the
      management of low back, neck, knee, and shoulder pain. METHODS: Evidence from
      randomized controlled trials (RCTs) and observational studies was identified and
      synthesized using methods defined by the Cochrane Collaboration that minimize
      bias by using a systematic approach to literature search, study selection, data
      extraction, and data synthesis. Meta-analyses were conducted where possible. The
      strength of evidence was graded as level I for RCTs or level II for nonrandomized
      studies. DEVELOPING RECOMMENDATIONS: An expert panel was formed by inviting
      stakeholder professional organizations to nominate a representative. This panel
      developed a set of criteria for grading the strength of both the evidence and the
      recommendation. The panel decided that evidence of clinically important benefit
      (defined as 15% greater relative to a control based on panel expertise and
      empiric results) in patient-important outcomes was required for a recommendation.
      Statistical significance was also required but was insufficient alone. Patient
      important outcomes were decided by consensus as being pain, function, patient
      global assessment, quality of life, and return to work, providing that these
      outcomes were assessed with a scale for which measurement reliability and
      validity have been established. VALIDATING THE RECOMMENDATIONS: A feedback survey
      questionnaire was sent to 324 practitioners from 6 professional organizations.
      The response rate was 51%. RESULTS: Eight positive recommendations of clinical
      benefit were developed. These recommendations were mainly in agreement with
      previous EBCPGs, although some were not covered by other EBCPGs. There was wide
      agreement with these recommendations from practitioners (greater than 75%
      agreement). For several interventions and indications (eg, thermotherapy,
      therapeutic ultrasound, massage, electrical stimulation, mechanical traction),
      there was a lack of evidence regarding efficacy. CONCLUSIONS: This methodology of
      developing EBCPGs provides a structured approach to assessing the literature and
      developing EBCPGs that incorporates clinicians' feedback and is widely acceptable
      to practicing clinicians. Further well-designed RCTs are warranted regarding the
      use of several interventions where evidence was insufficient to make
      recommendations.

PMID- 11589642
TI  - Philadelphia Panel evidence-based clinical practice guidelines on selected
      rehabilitation interventions for low back pain.
AB  - INTRODUCTION: A structured and rigorous methodology was developed for the
      formulation of evidence-based clinical practice guidelines (EBCPGs), then was
      used to develop EBCPGs for selected rehabilitation interventions for the
      management of low back pain. METHODS: Evidence from randomized controlled trials
      (RCTs) and observational studies was identified and synthesized using methods
      defined by the Cochrane Collaboration that minimize bias by using a systematic
      approach to literature search, study selection, data extraction, and data
      synthesis. Meta-analysis was conducted where possible. The strength of evidence
      was graded as level I for RCTs or level II for nonrandomized studies. DEVELOPING
      RECOMMENDATIONS: An expert panel was formed by inviting stakeholder professional
      organizations to nominate a representative. This panel developed a set of
      criteria for grading the strength of both the evidence and the recommendation.
      The panel decided that evidence of clinically important benefit (defined as 15%
      greater relative to a control based on panel expertise and empiric results) in
      patient-important outcomes was required for a recommendation. Statistical
      significance was also required, but was insufficient alone. Patient-important
      outcomes were decided by consensus as being pain, function, patient global
      assessment, quality of life, and return to work, providing that these outcomes
      were assessed with a scale for which measurement reliability and validity have
      been established. VALIDATING THE RECOMMENDATIONS: A feedback survey questionnaire
      was sent to 324 practitioners from 6 professional organizations. The response
      rate was 51%. RESULTS: Four positive recommendations of clinical benefit were
      developed. Therapeutic exercises were found to be beneficial for chronic,
      subacute, and postsurgery low back pain. Continuation of normal activities was
      the only intervention with beneficial effects for acute low back pain. These
      recommendations were mainly in agreement with previous EBCPGs, although some were
      not covered by other EBCPGs. There was wide agreement with these recommendations
      from practitioners (greater than 85%). For several interventions and indications
      (eg, thermotherapy, therapeutic ultrasound, massage, electrical stimulation),
      there was a lack of evidence regarding efficacy. CONCLUSIONS: This methodology of
      developing EBCPGs provides a structured approach to assessing the literature and
      developing guidelines that incorporates clinicians' feedback and is widely
      acceptable to practicing clinicians. Further well-designed RCTs are warranted
      regarding the use of several interventions for patients with low back pain where
      evidence was insufficient to make recommendations.

PMID- 11589643
TI  - Philadelphia Panel evidence-based clinical practice guidelines on selected
      rehabilitation interventions for knee pain.
AB  - INTRODUCTION: A structured and rigorous methodology was developed for the
      formulation of evidence-based clinical practice guidelines (EBCPGs), then was
      used to develop EBCPGs for selected rehabilitation interventions for the
      management of knee pain. METHODS: Evidence from randomized controlled trials
      (RCTs) and observational studies were identified and synthesized using methods
      defined by the Cochrane Collaboration that minimize bias by using a systematic
      approach to literature search, study selection, data extraction, and data
      synthesis. Meta-analysis was conducted where possible. The strength of evidence
      was graded as level I for RCTs or level II for nonrandomized studies. DEVELOPING
      RECOMMENDATIONS: An expert panel was formed by inviting stakeholder professional
      organizations to nominate a representative. This panel developed a set of
      criteria for grading the strength of both the evidence and the recommendation.
      The panel decided that evidence of clinically important benefit (defined as 15%
      greater relative to a control based on panel expertise and empiric results) in
      patient-important outcomes was required for a recommendation. Statistical
      significance was also required but was insufficient alone. Patient-important
      outcomes were decided by consensus as being pain, function, patient global
      assessment, quality of life, and return to work, providing that these outcomes
      were assessed with a scale for which measurement reliability and validity have
      been established. VALIDATING THE RECOMMENDATIONS: A feedback survey questionnaire
      was sent to 324 practitioners from 6 professional organizations. The response
      rate was 51%. RESULTS: Two positive recommendations of clinical benefit were
      developed: (1) transcutaneous electrical nerve stimulation (TENS) and therapeutic
      exercises were beneficial for knee osteoarthritis, and (2) there was good
      agreement with these recommendations from practitioners (73% for TENS, 98% for
      exercises). For several interventions and indications (eg, thermotherapy,
      therapeutic ultrasound, massage, electrical stimulation), there was a lack of
      evidence regarding efficacy. CONCLUSIONS: This methodology of developing EBCPGs
      provides a structured approach to assessing the literature and developing EBCPGs
      that incorporates clinicians' feedback and is widely acceptable to practicing
      clinicians. Further well-designed RCTs are warranted regarding the use of several
      interventions for patients with knee pain where evidence was insufficient to make
      recommendations.

PMID- 11589644
TI  - Philadelphia Panel evidence-based clinical practice guidelines on selected
      rehabilitation interventions for neck pain.
AB  - INTRODUCTION: A structured and rigorous methodology was developed for the
      formulation of evidence-based clinical practice guidelines (EBCPGs), then was
      used to develop EBCPGs for selected rehabilitation interventions for the
      management of neck pain. METHODS: Evidence from randomized controlled trials
      (RCTs) and observational studies was identified and synthesized using methods
      defined by the Cochrane Collaboration that minimize bias by using a systematic
      approach to literature search, study selection, data extraction, and data
      synthesis. Meta-analysis was conducted where possible. The strength of evidence
      was graded as level I for RCTs or level II for nonrandomized studies. DEVELOPING
      RECOMMENDATIONS: An expert panel was formed by inviting stakeholder professional
      organizations to nominate a representative. This panel developed a set of
      criteria for grading the strength of both the evidence and the recommendation.
      The panel decided that evidence of clinically important benefit (defined as 15%
      greater relative to a control based on panel expertise and empiric results) in
      patient-important outcomes was required for a recommendation. Statistical
      significance was also required but was insufficient alone. Patient-important
      outcomes were decided by consensus as being pain, function, patient global
      assessment, quality of life, and return to work, providing that these outcomes
      were assessed with a scale for which measurement reliability and validity have
      been established. VALIDATING THE RECOMMENDATIONS: A feedback survey questionnaire
      was sent to 324 practitioners from 6 professional organizations. The response
      rate was 51%. RESULTS: For neck pain, therapeutic exercises were the only
      intervention with clinically important benefit relative to a control (grade A for
      pain and function, grade B for patient global assessment). There was good
      agreement with this recommendation from practitioners (93%). For several
      interventions and indications (eg, thermotherapy, therapeutic ultrasound,
      massage, electrical stimulation), there was a lack of evidence regarding
      efficacy. CONCLUSIONS: This methodology of developing EBCPGs provides a
      structured approach to assessing the literature and developing guidelines that
      incorporates clinicians' feedback and is widely acceptable to practicing
      clinicians. Further well-designed RCTs are warranted regarding the use of several
      interventions for patients with neck pain where evidence was insufficient to make
      recommendations.

PMID- 11589646
TI  - Clinical diagnosis of sacroiliac joint dysfunction.

PMID- 11589645
TI  - Philadelphia Panel evidence-based clinical practice guidelines on selected
      rehabilitation interventions for shoulder pain.
AB  - INTRODUCTION: A structured and rigorous methodology was developed for the
      formulation of evidence-based clinical practice guidelines (EBCPGs), then was
      used to develop EBCPGs for selected rehabilitation interventions for the
      management of shoulder pain. METHODS: Evidence from randomized controlled trials
      (RCTs) and observational studies was identified and synthesized using methods
      defined by the Cochrane Collaboration that minimize bias by using a systematic
      approach to literature search, study selection, data extraction, and data
      synthesis. Meta-analysis was conducted where possible. The strength of evidence
      was graded as level I for RCTs or level II for nonrandomized studies. DEVELOPING
      RECOMMENDATIONS: An expert panel was formed by inviting stakeholder professional
      organizations to nominate a representative. This panel developed a set of
      criteria for grading the strength of both the evidence and the recommendation.
      The panel decided that evidence of clinically important benefit (defined as 15%
      greater relative to a control based on panel expertise and empiric results) in
      patient-important outcomes was required for a recommendation. Statistical
      significance was also required but was insufficient alone. Patient-important
      outcomes were decided by consensus as being pain, function, patient global
      assessment, quality of life, and return to work, providing that these outcomes
      were assessed with a scale for which measurement reliability and validity have
      been established. VALIDATING THE RECOMMENDATIONS: A feedback survey questionnaire
      was sent to 324 practitioners from 6 professional organizations. The response
      rate was 51%. RESULTS: Only 1 positive recommendation of clinical benefit was
      developed. Ultrasound provided clinically important pain relief relative to a
      control for patients with calcific tendinitis in the short term (less than 2
      months). There was good agreement with this recommendation from practitioners
      (75%). For several interventions and indications (eg, thermotherapy, therapeutic
      exercise, massage, electrical stimulation, mechanical traction), there was a lack
      of evidence regarding efficacy. CONCLUSIONS: This methodology of developing
      EBCPGs provides a structured approach to assessing the literature and developing
      EBCPGs that incorporates clinicians' feedback and is widely acceptable to
      practicing clinicians. Further well-designed RCTs are warranted regarding the use
      of several interventions for patients with shoulder pain where evidence was
      insufficient to make recommendations.

PMID- 11589647
TI  - Therapeutic intensive seizure analysis (TISA) in presurgical evaluation of
      Losigamone.
AB  - OBJECTIVE: The new method TISA was used to evaluate Losigamone efficacy. METHODS:
      Sixteen patients with pharmacoresistant partial seizures undergoing presurgical
      evaluation were randomized in this double-blind, placebo-controlled, parallel
      group Losigamone monotherapy study under continuous video-EEG monitoring.
      Duration (in s, of each seizure and each ictal sign), intensity (grade zero to
      three), N/24h (number of seizures and ictal signs per 24 h), D/24h (seconds per
      24 h covered by seizures and ictal signs) and seizure free intervals were
      recorded. RESULTS: A total of 246 seizures were intensively analyzed. The
      duration and intensity of all seizures improved more in the active treatment
      group than in the placebo group. There was a statistically significant
      superiority in the duration of the seizure free interval in the Losigamone group.
      Ictal signs such as oro-alimentary automatisms and fumbling were improved during
      Losigamone treatment. CONCLUSION: Losigamone has a preferred inhibitory effect on
      propagated epileptic activity. TISA is a sensitive method for evaluation of the
      selective effects of AEDs.

PMID- 11589648
TI  - Seizure recurrence in adults after a newly diagnosed unprovoked epileptic
      seizure.
AB  - PURPOSE: To investigate the risk of seizure recurrence after a newly diagnosed
      unprovoked epileptic seizure in an adult population-based cohort. MATERIAL AND
      METHODS: A total of 107 patients aged >or=17 years with a newly diagnosed
      unprovoked epileptic seizure (index seizure) were prospectively identified for
      the period 1985-87. Patients were followed until the date of death or to the end
      of 1996 with a median follow-up of 10.3 years for surviving cases. Overall
      cumulative recurrence rates and possible influencing variables were calculated.
      RESULTS: At 750 days after the index seizure the recurrence was 58%, and after
      that no events occurred. Recurrence risk was significantly higher when index
      seizure was remote symptomatic or preceded by two or more seizures. No other
      study variable predicted seizure recurrence. CONCLUSION: Etiology and the
      occurrence of seizures before the index seizure after a newly diagnosed
      unprovoked epileptic seizure predict seizure recurrence. Thus, particular
      consideration should be given to these factors in the decision of whether or not
      to initiate antiepileptic treatment.

PMID- 11589649
TI  - The prevalence of multiple sclerosis in the city of Sao Paulo, Brazil, 1997.
AB  - July 1, 1997 was stipulated as the day for estimating the prevalence of multiple
      sclerosis within the city of Sao Paulo. The patients were identified via various
      sources, including associated universities and magnetic resonance services of the
      city of Sao Paulo. The area covered by the study has a population of 9,380,000,
      mainly white and of European origin, with a large number of immigrants from Spain
      and Portugal. The patients were classified in accordance with the criteria of
      Poser et al. (1983), and only those with defined multiple sclerosis were
      registered. The study gave a prevalence of 15.0/10(5) inhabitants, or three times
      the value obtained in a similar study in 1990. This increase reveals the larger
      number of cases encompassed by the study, and is attributed to the use of more
      detailed recording methods, improvements in diagnosis, and better conditions for
      treatment.

PMID- 11589650
TI  - Cognitive correlates of supratentorial atrophy on MRI in multiple sclerosis.
AB  - OBJECTIVES: We aimed to investigate associations between neuropsychological
      indices and normalized volumes of supratentorial structures, and the area of the
      corpus callosum. MATERIALS AND METHODS: We studied 40 patients with clinically
      definite MS, using 3D-acquired MRI (MPRAGE, Magnetization Prepared Rapid
      Acquisition Gradient Echo) and stereology. Subjects underwent a
      neuropsychological battery interrogating multiple cognitive domains, from which a
      global Cognitive Index Score (CIS) was derived. RESULTS: White matter volumes
      were significantly correlated with CIS (rho= -0.59, P<0.0001) and with many of
      the individual cognitive tests. CIS was also significantly correlated with the
      corpus callosal area (rho= -0.49, P<0.002). Grey matter volumes did not
      significantly correlate with any cognitive test. CONCLUSIONS: These
      volume/function relationships presumably reflect the effects of subcortical
      axonal and myelin loss on the neural networks that subserve cognition. If serial
      MRI volume estimations can index accumulating cognitive deficits, this simple
      technique may be useful in therapeutic trials.

PMID- 11589651
TI  - Machado-Joseph disease in South Brazil: clinical and molecular characterization
      of kindreds.
AB  - OBJECTIVE: To examine the clinical, genetic, and molecular characteristics of a
      group of MJD patients recently identified in the southernmost state of Brazil,
      and compare these data with studies from the literature. METHODS: Some 62
      individuals from 35 families, mostly of Azorean ancestry, had their clinical data
      and their MJD1 expanded regions examined. RESULTS: The present patients had an
      earlier age of onset, on average, than Portuguese-Azorean cases. Their survival,
      proportion of types, average anticipation, proportion of affected versus non
      affected siblings, neurological signs and molecular findings are similar to those
      observed in patients previously described. Type 1 patients with male transmission
      showed worse anticipations than type 1 patients with female transmission.
      Patients with type 1 had also larger CAG expansions than other patients.
      CONCLUSIONS: The Brazilian origin seemed to affect the age of onset. We also
      noted that there were no differences other than the neurological between types 2
      or 3, since both are similar in age of onset, disease duration and length of CAG
      repeats. We addressed the question of maintaining or not subtypes 2 and 3
      separated, among patients with genetic and geographical backgrounds like the
      presented patients here.

PMID- 11589652
TI  - Mortality from amyotrophic lateral sclerosis in Finland, 1986-1995.
AB  - OBJECTIVE: To study the possible changes, between 1986 and 1995, in the mortality
      due to amyotrophic lateral sclerosis (ALS) among Finnish patients. MATERIALS AND
      METHODS: A total of 1000 deaths from ALS were extracted from the Finnish Death
      Certificate Register for the study years. General population data were obtained
      from the Statistical Yearbooks of Finland. RESULTS: From a death rate of
      1.54/100,000 in 1986 an increase to 2.27/100,000 in 1995 was observed. Since 1963
      the number of ALS deaths has tripled. The documented increased life-expectancy in
      Finland correlates with the ALS death rate, at least partly explaining the
      increase. Contrary to other countries, on the whole equal numbers of men and
      women died of ALS. Women tended to be older than men when they died of ALS.
      CONCLUSION: In accordance with other countries ALS mortality in Finland is
      steadily increasing.

PMID- 11589653
TI  - Reinnervation of dystrophic muscles.
AB  - OBJECTIVE: To analyse the regenerating capability of the peripheral nerve fibers
      and the capability of the muscle fibers to accept the regenerating and new nerve
      sprouts in myotonic dystrophy (MD). MATERIAL AND METHODS: One male, aged 58
      years, diagnosed of MD at the age of 30 years, suffered neuralgic amyotrophy in
      the right shoulder girdle 4 weeks before admission. Needle EMG and nerve
      conduction studies were performed on admission and 6, 12, and 18 months later.
      RESULTS: On admission there were atrophy and absence of voluntary contraction in
      deltoids, supra- and infraspinatus muscles. EMG showed abundant fibrillations,
      positive sharp waves and myotonic bursts in these muscles without voluntary
      activity, consistent with axonal neuropathy of both axillary and suprascapular
      nerves. The follow-up showed signs of reinnervation 6 months later and slight
      loss of long duration and high amplitude MUPs at 18 months of evolution, with
      good clinical recovery. This is compatible with chronic neurogenic atrophy,
      presumably as an expression of type grouping. CONCLUSIONS: The reinnervation
      capability of the nerve fibers and the capability of muscle fibers membrane to
      accept regenerating and new nerve sprout remain in MD. Myotonic bursts persist
      after total denervation.

PMID- 11589654
TI  - Acute transverse myelitis and Guillain-Barre overlap syndrome with serological
      evidence for mumps viraemia.
AB  - Both acute transverse myelitis (ATM) and Guillain-Barre syndrome (GBS) occur as
      rare associations with mumps viraemia but to our knowledge, concurrent ATM and
      GBS related to mumps has only been reported once previously. We describe the case
      of a young woman presenting with confusion and collapse 2 weeks after a flu-like
      illness. An initial diagnosis of transverse myelitis was made on the basis of the
      clinical findings and radiological evidence of a swollen spinal cord with uniform
      high signal change on T2 weighted MRI. The patient was treated with intravenous
      methylprednisolone without significant recovery. The diagnosis was later revised
      to include GBS on the basis of worsening facial diplegia in the setting of a
      flaccid tetraparesis, and neurophysiological evidence of a sensorimotor axonal
      polyradiculoneuropathy. Acute mumps viraemia was confirmed on serological
      grounds. The patient made an improvement in ventilatory capacity with intravenous
      immunoglobulin treatment.

PMID- 11589655
TI  - Bulbar-onset amyotrophic lateral sclerosis in a patient with Chiari I
      malformation.
AB  - We report on a patient with bulbar-onset, clinically defined, sporadic
      amyotrophic lateral sclerosis (ALS) who also showed a Chiari I malformation. This
      malformation, otherwise asymptomatic, was detected during the diagnostic work-up
      for ALS. To our knowledge this is the first report of an association between
      these two relatively uncommon disorders. Since our patient worked for many years
      as a bus-driver and because the ALS symptoms began in the brainstem region, we
      suggest that his hindbrain anomaly, along with the mechanical stress on the spine
      and cranio-vertebral junction due to the daily driving, might have played a role
      in the region-specific onset of ALS.

PMID- 11589656
TI  - Myasthenia gravis and Waldenstrom's macroglobulinemia: a case report and review
      of the literature.
AB  - An elderly man with ocular type myasthenia gravis (MG) was found to have
      monoclonal gammopathy (IgM). Waldenstrom's macroglobulinemia (WM) was proven
      later. This is the second case report of MG associated with WM. However, this
      case is unique due to the presence of anti-acetylcholine receptor (anti-AChR)
      antibody (IgG). MG is considered to be an autoimmune disease and WM an
      immunoproliferative disorder. The association of MG and WM is not clear.

PMID- 11589657
TI  - 21st century molecular biology in urology.

PMID- 11589658
TI  - The value of current diagnostic tests in prostate cancer screening.

PMID- 11589659
TI  - Lymphadenectomy for squamous cell carcinoma of the penis. Part 1: diagnosis of
      lymph node metastasis.

PMID- 11589660
TI  - Lymphadenectomy for squamous cell carcinoma of the penis. Part 2: the role and
      technique of lymph node dissection.

PMID- 11589662
TI  - The development of urology in the 21st century.

PMID- 11589663
TI  - Classical vs reverse pharmacology in drug discovery.

PMID- 11589664
TI  - The search for drug target molecules from genomics.

PMID- 11589665
TI  - Lower urinary tract symptoms in community-dwelling women: defining diurnal and
      nocturnal frequency and 'the incontinence case'.

PMID- 11589666
TI  - Clinical experience in lower urinary tract symptoms.

PMID- 11589667
TI  - The role of alpha1-adrenergic receptor subtypes in lower urinary tract symptoms.

PMID- 11589668
TI  - Stem cell differentiation within the human prostate epithelium: implications for
      prostate carcinogenesis.

PMID- 11589669
TI  - New therapeutic concepts in prostate cancer.

PMID- 11589671
TI  - Controversies in the clinical evaluation of active thyroid-associated
      orbitopathy: use of a detailed protocol with comparative photographs for
      objective assessment.
AB  - Despite many learned publications over recent decades, the assessment of active
      thyroid-associated orbitopathy (TAO) remains difficult and controversial. There
      are no biochemical, immunological or imaging investigations which can identify
      active disease reliably, and clinical assessment is still of paramount
      importance. We therefore review the strengths and weaknesses of all methods of
      clinical assessment. A new atlas for clinical assessment of soft tissue signs has
      been developed, and its reproducibility assessed. It details a suggested protocol
      that could help standardize descriptions of TAO and allow more objective
      assessment of its activity and severity. This is relevant to general
      endocrinologists, who have a crucial role in the identification of patients who
      require ophthalmological assessment. Certain aspects are more relevant to
      ophthalmologists and endocrinologists who have a special clinical and research
      interest in TAO. Unless a reproducible system of assessment is devised and widely
      adopted, it will remain difficult to interpret research meaningfully,
      particularly if results appear to contradict.

PMID- 11589672
TI  - Are patients with acromegaly at high risk for dysrhythmias?

PMID- 11589673
TI  - Marked improvement in cardiovascular function after successful transsphenoidal
      surgery in acromegalic patients.
AB  - OBJECTIVE: Transsphenoidal surgery results in biochemical remission of acromegaly
      in 45-80% of patients; however, few studies have addressed the impact of
      transsphenoidal surgery on cardiovascular function in acromegalic patients. The
      aim of this prospective study was to investigate the effects of postoperative
      GH/IGF-I normalization on echocardiographic parameters and blood pressure (BP) in
      a series of patients with active acromegaly. DESIGN: An open prospective study.
      PATIENTS: Thirty newly diagnosed acromegalic patients undergoing transsphenoidal
      surgery. MEASUREMENTS: Doppler echocardiography and 24-h ambulatory blood
      pressure monitoring were performed before and 6 months after transsphenoidal
      surgery. RESULTS: Fifteen patients were considered to be well controlled
      postoperatively (group A), as defined by normal age-corrected IGF-I levels and
      glucose-suppressed GH levels less than 2 mU/l, the remaining 15 patients being
      considered as poorly controlled (group B). In group A, a postoperative decrease
      of left ventricular mass index was observed (104.4 +/- 6.6 vs. 127.1 +/- 7.7
      g/m2; P < 0.001), associated with an improvement of some indices of diastolic
      function, such as an increase of the early/late transmitral peak flow velocity (P
      < 0.05) and a decrease of isovolumic relaxation time (P < 0.01). No significant
      change was observed in group B. A significant decrease of 24-h systolic BP was
      also observed in group A (P < 0.05) and five of six patients normalized their BP
      circadian rythm. In contrast, a nonsignificant increase in BP values, with a
      persistent blunted BP profile where present, was observed in group B.
      CONCLUSIONS: We conclude that successful transsphenoidal surgery is able to
      induce a significant improvement in some cardiac parameters and a slight
      reduction in systolic blood pressure in acromegalic patients.

PMID- 11589675
TI  - Double-blind placebo-controlled trial of oral dehydroepiandrosterone in patients
      with advanced HIV disease.
AB  - OBJECTIVE: Plasma levels of dehydroepiandrosterone sulphate (DHEA-S) decrease
      with the progression of HIV disease. Here, we report on the efficacy and safety
      of the oral administration of DHEA as replacement therapy, in patients with
      advanced HIV disease, in a trial that was primarily aimed at assessing quality of
      life. DESIGN: The trial was randomized and double-blind. Thirty-two patients were
      allocated to either DHEA 50 mg per day for 4 months (n = 14) or a matching
      placebo (n = 18). Clinical data, virological and immunological surrogate markers
      of HIV infection, plasma levels of DHEA-S and the Medical Outcomes Study HIV
      Health Survey (MOS-HIV) quality of life scale were recorded every month. RESULTS:
      The mean age of the patients was 40 +/- 11 years. The mean CD4 cell count at
      baseline was 32.5 +/- 32.4 x 10(6)/l. The mean DHEA-S plasma level at baseline
      was 5.23 +/- 0.76 micromol/l. No side-effects related to DHEA occurred during the
      study. A statistically significant increase in the levels of DHEA-S was observed
      in the treated group throughout the study (P < 0.01). A significant improvement
      in the Mental Health and Health Distress dimension of MOS-HIV was observed in the
      DHEA treated group; P = 0.001 and 0.004, respectively. No change in CD4 cell
      counts was seen during follow-up. CONCLUSIONS: The administration of DHEA in
      patients with advanced HIV infection results in improved mental function scores
      as assessed by the MOS-HIV quality of life scale.

PMID- 11589674
TI  - Randomized placebo-controlled trial of testosterone replacement in men with mild
      Leydig cell insufficiency following cytotoxic chemotherapy.
AB  - OBJECTIVE: Testosterone deficiency is associated with significant morbidity, and
      androgen replacement in overt hypogonadism is clearly beneficial. However, there
      are few data concerning the response to therapy in young men with mild
      testosterone deficiency. DESIGN AND PATIENTS: We have identified a cohort of 35
      men, mean age 40.9 years, with mild Leydig cell dysfunction, defined by a raised
      LH level (LH >or= 8 IU/l) and a testosterone level in the lower half of the
      normal range or frankly subnormal (testosterone < 20 nmol/l), following treatment
      with cytotoxic chemotherapy for malignancy. Patients were assigned randomly to 12
      months treatment with transdermal testosterone (n = 16) (Andropatch 2.5 mg
      patches, 1-2 patches per day) or placebo patches (n = 19) in a single blinded
      manner. MEASUREMENTS: Measurements of bone mineral density (BMD) and body
      composition were performed at baseline, 6 months and 12 months using single and
      dual energy X-ray absorptiometry (SXA, DXA). In addition, spinal BMD was assessed
      at baseline and 12 months by quantitative CT (QCT). Subjects were reviewed at 3
      monthly intervals; at each visit blood was taken for measurement of testosterone,
      SHBG, LH, FSH, oestradiol, lipids and IGF-1 and patients completed three
      questionnaires which assessed energy levels, mood and sexual function. RESULTS:
      Total testosterone and calculated free testosterone increased significantly in
      the testosterone-treated group compared with the placebo-treated group (13.3
      nmol/l and 342.9 pmol/l at baseline compared with 17.3 nmol/l and 454.8 pmol/l
      during the study period in the testosterone-treated group; P = 0.05 and P = 0.02,
      respectively). LH was suppressed into the normal range in 15 of the 16
      testosterone-treated men and mean LH significantly reduced from 11.1 IU/l at
      baseline to 6.8 IU/l during the study. There was no significant change in BMD at
      the hip, spine or forearm and no change in fat or lean body mass. There was a
      significant reduction in physical fatigue in the testosterone-treated group
      compared with the placebo-treated group (P = 0.008) and a borderline improvement
      in activity score (P = 0.05). There were no significant effects of treatment on
      mood or sexual function. Neither oestradiol nor IGF-1 levels differed between the
      two groups during the study. There was no significant change in mean total
      cholesterol, HDL cholesterol or triglyceride levels, but there was a small, but
      significant reduction in LDL cholesterol levels in the testosterone-treated group
      compared with the placebo group (P = 0.02). CONCLUSIONS: These results suggest
      that testosterone therapy in young men with raised LH levels and low/normal
      testosterone levels does not result in significant changes in BMD, body
      composition, lipids or quality of life, apart from a reduction in physical
      fatigue and a small reduction in LDL cholesterol. This implies that mild
      hypogonadism defined on this basis is not of clinical importance in the majority
      of men, and that androgen replacement cannot be recommended for routine use in
      these patients.

PMID- 11589676
TI  - Sensitive LH and FSH assays for monitoring low serum levels in men undergoing
      steroidal contraception.
AB  - BACKGROUND AND OBJECTIVES: Current immunoassays for detecting serum FSH and LH
      are not sufficiently sensitive to detect the markedly reduced levels in men
      undergoing steroidal hormonal treatment for contraceptive purposes. The purpose
      of this study was to increase the sensitivity of available LH and FSH
      immunofluorometric (Delfia) assays in order to allow a better understanding of
      the importance of gonadotrophin suppression in achieving the optimal suppression
      of sperm count. DESIGN AND PATIENTS: Assay conditions were modified by increasing
      serum sample volume, the inclusion of either FSH- or LH-depleted serum to reduce
      the resulting matrix effects and extending incubation times. The microassays were
      applied to serum from 10 men administered testosterone enanthate with or without
      depot medroxyprogesterone acetate for 12 weeks as part of a contraceptive trial.
      RESULTS: The assay sensitivities were increased to 0.005 IU/l for LH and 0.010
      IU/l for FSH, representing a five- to six-fold increase in sensitivity compared
      with existing assays. In the clinical trial, serum LH levels were suppressed to
      near or below the level of assay detection (mean 0.014 IU/l < 0.4% of
      pretreatment values) while in eight of 10 men, plasma FSH levels were detectable
      (0.04-0.07 IU/l, 1-5% of pretreatment values). These FSH levels would not have
      been detected by current assays. CONCLUSIONS: The increased sensitivities of the
      LH and FSH assays enabled the detection of gonadotrophins that were < 0.4% of
      pretreatment serum levels. Using these methods, serum LH was suppressed to
      nondetectable or near nondetectable levels while serum FSH was highly suppressed
      but still detectable in the majority of men undergoing steroidal treatment for
      contraceptive purposes.

PMID- 11589677
TI  - Plasma leptin concentrations are associated with bone mineral density and the
      presence of vertebral fractures in postmenopausal women.
AB  - OBJECTIVE: Although total fat body mass (FM) is considered to be one of the major
      determinants of bone mass, the mechanism by which FM and bone mass are positively
      correlated remains unclear. Leptin, the product of the obese (ob) gene, is
      secreted from adipocytes and its plasma levels are known to be positively
      correlated with %fat (FM divided by total body weight). There is recent evidence
      suggesting that leptin directly stimulates osteoblastic differentiation. Thus it
      is possible that the anabolic action of this hormone on bone may participate in
      the positive correlation between FM and bone mass. In this study, we analysed the
      relationships between either plasma leptin levels or %fat vs. bone mineral
      density (BMD) values as well as the presence of vertebral compression fractures,
      and evaluated whether or not plasma leptin levels were associated with BMD or
      bone fragility in a manner independent of FM. PATIENTS: One hundred and thirty
      nine postmenopausal women (age 48-78 years, mean 62.5), who visited our
      outpatient clinic for the evaluation of osteoporosis. DESIGN AND MEASUREMENTS:
      Plasma concentrations of leptin after an overnight fast were measured by
      radioimmunoassay. BMD values were measured by dual-energy X-ray absorptiometry
      (DXA) at the lumbar spine, femoral neck and whole body. Distal one-third of
      radius BMD was measured by single photon absorptiometry (SPA). Vertebral
      fractures were assessed by lateral thoracic and lumbar spine radiographs.
      RESULTS: Although neither plasma leptin levels nor %fat correlated with age,
      there was a significant positive correlation between plasma leptin levels and
      %fat (r = 0.563, P < 0.001). Plasma leptin levels were significantly and
      positively correlated with BMD values at all skeleton sites measured, and
      multiple regression analysis revealed that this positive relationship was still
      observed with BMD values of the femoral neck and of the whole body, even after
      %fat and age were taken into account. Moreover, plasma leptin levels but not %fat
      were significantly lower in women with vertebral fractures than in those without
      fractures. When multiple logistic regression analysis was performed with either
      plasma leptin value or %fat employed as independent variables, plasma leptin
      values but not %fat were selected as an index affecting the presence of vertebral
      fractures. CONCLUSION: Our study showed that plasma leptin levels but not %fat
      are associated with BMD and the presence of vertebral fractures in postmenopausal
      women, suggesting that circulating leptin might play a physiological role in
      maintaining bone mass as well as better bone quality.

PMID- 11589678
TI  - Elevated plasma non-esterified fatty acid levels and insulin secretion in non
      diabetic relatives of type 2 diabetic patients.
AB  - OBJECTIVE: High non-esterified fatty acid (NEFA) levels impair glucose-stimulated
      insulin secretion from islets derived from non-diabetic Zucker rats that are
      genetically predisposed to diabetes. We therefore examined the effect of elevated
      plasma NEFA levels on insulin secretion in non-diabetic first-degree relatives of
      type 2 diabetic patients who are at increased risk of developing diabetes.
      SUBJECTS AND STUDY DESIGN: Normal glucose tolerant relatives (n = 9) and control
      subjects with no family history of diabetes were pair-matched for age, sex, body
      mass index (BMI), insulin sensitivity and early insulin response during an oral
      glucose tolerance test (OGTT). Plasma NEFA levels were raised from 0 to 340
      minutes by the infusion of 20% Intralipid and heparin. From 180 minutes, insulin
      secretion rates (IRSs) were assessed by stepped low-dose glucose infusion.
      RESULTS: The mean (geometric mean +/- 95% CI) NEFA levels were comparable between
      relatives and control subjects (2.7 [2.1-3.6] and 2.1 [1.7-2.7] mmol/l, paired
      analysis, NS). Similarly, plasma glucose levels achieved at each glucose infusion
      step were comparable between the groups. However, there were no significant
      differences between the groups for ISR throughout the study. CONCLUSIONS:
      Sustained elevation of plasma non-esterified fatty acid levels does not decrease
      insulin secretion in non-diabetic relatives of type 2 diabetic patients, and is
      therefore unlikely to be important in the development of the impaired pancreatic
      beta-cell function in type 2 diabetes mellitus.

PMID- 11589679
TI  - Assessment of selective arterial calcium stimulation and hepatic venous sampling
      to localize insulin-secreting tumours.
AB  - OBJECTIVE: Non-invasive localization modalities such as ultrasound, computed
      tomography (CT) or magnetic resonance imaging (MRI) often fail to localize
      insulinomas smaller than 2 cm in diameter. Recent studies have shown that the
      selective arterial stimulation and hepatic venous sampling (ASVS) technique using
      intra-arterial calcium as the insulin secretagogue facilitates the
      regionalization of such occult insulinomas. This study assesses the sensitivity
      of ASVS in localizing insulin-secreting tumours. SUBJECTS AND METHODS: Eleven
      consecutive patients (8 women), aged 29-82 years, were studied over the past 4
      years at our hospital. Hyperinsulinaemic hypoglycaemia due to an insulin
      secreting tumour was proven in all patients. Calcium gluconate (0.025 mEq/kg body
      weight) was injected directly into the arteries supplying the pancreas and the
      liver. Insulin levels were measured in samples taken from the right hepatic vein
      before and 30, 60 and 120 s after each injection. The ASVS technique was
      performed in all 11 patients; the results were compared with the surgical
      findings in 10 patients and the autopsy findings in 1 case. The ASVS results were
      also compared with the findings of other, previously performed imaging
      modalities. RESULTS: ASVS correctly localized 4 insulin-secreting tumours to the
      head, 3 to the body, 1 to the tail, 2 to the tail or body of the pancreas and 1
      to the liver. Thus, the sensitivity was 100% (11/11) whereas other localization
      techniques were less sensitive: 7/11 tumours were detected by angiography, 4/8 by
      endosonography, 3/8 by CT and 1/6 by MRI. Insulinomas (confirmed by histological
      examination), sized 4-25 mm, were found in 10 patients. All were cured by
      selective surgery and remained free of hypoglycaemia over the next 1-4 years of
      follow-up. An insulin-secreting neuroendocrine tumour in the liver was documented
      in 1 case at autopsy. CONCLUSIONS: Arterial stimulation and hepatic venous
      sampling is a very sensitive technique for preoperative localization of insulin
      producing tumours. It can help to plan minimally invasive surgery and to select
      an appropriate strategy for patients suffering from malignant tumours in others.

PMID- 11589680
TI  - Characterization of two novel mutations in the glucocorticoid receptor gene in
      patients with primary cortisol resistance.
AB  - OBJECTIVE: Primary glucocorticoid resistance is characterized by decreased
      sensitivity to cortisol signalling. We have performed genetic analysis of the
      glucocorticoid receptor (GR) gene in 12 unrelated patients with primary cortisol
      resistance as defined by a pathological dexamethasone suppression test. METHODS:
      Exon specific polymerase chain reaction amplification of the GR gene and
      sequencing of each exon was carried out. The two mutations were characterized in
      vitro in terms of glucocorticoid driven reporter gene activity in a transient
      transfection assay and in a ligand binding assay. Molecular modelling of the
      R477H mutant was performed based on the X-ray structure of the GR-DNA binding
      domain. RESULTS: Two novel mutations in the GR gene were found: R477H in the DNA
      binding domain which is the first reported mutation in that region of the human
      GR gene and G679S in the ligand binding domain. The R477H mutation showed no
      transactivating capacity, whereas the G679S mutation had reduced transactivation
      capacity compared to the wild-type (wt) GR. When tested for ligand binding
      capacity, the G679S mutation had 50% binding affinity compared to the wt GR. The
      effect of the point mutation R477H was deduced by a comparison between the wt
      structure and the model of the mutant. The wt GR has direct and water mediated
      contact with the phosphate groups of the glucocorticoid responsive element (GRE)
      whereas, in the model, the mutation R477H has no contact with the GRE. The G679S
      mutation is located on the surface of the ligand binding domain, at a distance
      from the steroid-binding site. A previously reported polymorphism, AAT to AAC at
      amino acid position 766, was found in four of the patients. CONCLUSIONS: In two
      of 12 patients with clinical glucocorticoid resistance, mutant forms of GR could
      be found. The glucocorticoid resistance in vivo in these two patients corresponds
      to impaired function of the two mutated GR forms in two in vitro assays. The
      relevance of the conservative polymorphism for the glucocorticoid insensitivity
      noted in these patients remains to be clarified.

PMID- 11589681
TI  - Association of polymorphic alleles of the calcium-sensing receptor gene with the
      clinical severity of primary hyperparathyroidism.
AB  - OBJECTIVE: Primary hyperparathyroidism (pHPT) is a heterogeneous disease in its
      clinical course and severity. Previous studies have suggested an association
      between the clinical severity of pHPT and the genotypes of vitamin D receptor,
      oestrogen receptors and PTH molecules. The Ca-sensing receptor (CaR) is activated
      by an extracellular calcium ion and controls PTH secretion, and thus
      polymorphisms of CaR might be associated with the magnitude of PTH secretion and
      the clinical severity of pHPT. In this study, we examined the relationship
      between CaR polymorphisms and biochemical markers in pHPT patients. METHODS: We
      analysed 105 Japanese pHPT patients (85 females and 20 males; mean age 55.6 +/-
      14.0 years). We determined the CaR genotypes of G990R and intron 5 polymorphisms
      with genomic DNA extracted from peripheral lymphocytes. The intron 5 polymorphism
      was defined as T/T, T/C and C/C. RESULTS: In the G990R polymorphism, serum levels
      of both intact PTH and alkaline phosphatase (ALP) were significantly higher and
      the serum level of phosphorus was significantly lower in the RR group than in the
      GG group. In the intron 5 polymorphism, the T/T group showed significantly lower
      serum levels of intact PTH and Ca. Furthermore, patients with both the codon 990
      RR and the intron 5 C allele (the RRC(+) group) had significantly higher serum
      levels of intact PTH and ALP than did the other patients. CONCLUSIONS: The
      present study is the first to show that CaR polymorphisms of G990R and intron 5
      were closely associated with the magnitude of PTH secretion and/or PTH
      degradation as well as the clinical severity in pHPT patients.

PMID- 11589682
TI  - TSH-receptor antibody measurement for differentiation of hyperthyroidism into
      Graves' disease and multinodular toxic goitre: a comparison of two competitive
      binding assays.
AB  - OBJECTIVES: Graves' disease is characterized by stimulating autoantibodies to the
      TSH-receptor (TRAb). The aim of this study was to compare the performance of a
      new TRAb assay based on competitive binding to recombinant human TSH-receptors (H
      TRAb) with an assay employing purified porcine TSH-receptors (P-TRAb).
      Furthermore, to evaluate the applicability of the H-TRAb assay to discriminate
      between patients with hyperthyroidism due to Graves' disease (GD) and
      multinodular toxic goitre (MNTG). DESIGN AND MEASUREMENTS: H-TRAb and P-TRAb were
      measured in patients with newly diagnosed hyperthyroidism due to GD (n = 106) and
      MNTG (n = 94). For comparison, TRAb was measured in patients with primary
      autoimmune hypothyroidism, euthyroid subjects with an enlarged thyroid gland by
      ultrasound, and healthy controls (n = 100 for each group). Patients were
      consecutively included from a population survey. RESULTS: If the cut-off values
      recommended by the manufacturer for TSH-receptor antibody positivity were used
      for evaluation, the sensitivity of the H-TRAb assay vs. the P-TRAb assay in
      diagnosing GD was: 95.3/67.9% (P < 0.001). Specificity was (H/P-TRAb): 99/99%.
      The sensitivity of P-TRAb was increased if the upper 97.5% limit of measurements
      in controls was used as cut-off (H-TRAb vs. P-TRAb: 95.3/80.2%, P < 0.001).
      Specificity (H/P-TRAb): 98/98%. The difference between assay performance may
      partly be due to a better technical performance of the H-TRAb assay with more
      reliable results in the low range of measurements. However, even in GD patients
      with clearly measurable TRAb, 25% had a P-TRAb < 50% of the value expected from
      the H-TRAb measurement. This suggests that a subgroup of patients produce TRAb
      with a higher affinity for the human than the porcine TSH receptor. A relatively
      high proportion of patients with MNTG were TRAb positive (H-TRAb/P-TRAb: 17/9%).
      Characteristics of H-TRAb positive and negative MNTG patients were compared.
      There was no difference between size of thyroid gland and number of nodules by
      ultrasonography. H-TRAb positive patients had significantly higher serum T4 and
      T3 and a greater number were TPO-Ab positive. CONCLUSIONS: H-TRAb diagnosed
      Graves' disease with a high sensitivity and specificity than P-TRAb. The high
      occurrence of TRAb in multinodular toxic goitre might in part reflect an overlap
      between Graves' disease and multinodular toxic goitre in some patients.

PMID- 11589683
TI  - Prevalence of gestational thyrotoxicosis in Asian women evaluated in the 8th to
      14th weeks of pregnancy: correlations with total and free beta human chorionic
      gonadotrophin.
AB  - OBJECTIVES: The prevalence of gestational transient thyrotoxicosis (GTT) in
      Europeans evaluated during the 8th to 14th weeks of pregnancy is 2-3%. However,
      there is evidence that GTT may be more common in some Asian populations. The aims
      of this study were to evaluate the prevalence of thyroid hormone abnormalities in
      Asian women in their 8th to 14th weeks of pregnancy using highly sensitive free
      T4 and TSH assays and to correlate these with total and free beta-hCG levels.
      DESIGN AND PATIENTS: One hundred and eighty-four consecutive unselected Asian
      (Singaporean) pregnant women seen at ante-natal clinics for the first time and
      who were in their 8th to 14th weeks of pregnancy were tested. MEASUREMENTS: Serum
      free T4, free T3, TSH, total beta-hCG and free beta-HCG levels were measured on
      the Vitros ECi system (Johnson & Johnson Ortho-Clinical Diagnostics, Amersham,
      UK) which employs chemiluminescent immunochemical technology. This free T4 assay
      is free of biases related to serum binding capacity. The TSH assay used was a
      third generation assay. Thyrotrophin-receptor antibody (TRAb) levels were
      measured using LUMItest TRAK (BRAHMS Diagnostica, Berlin, Germany). RESULTS: Two
      subjects (1.1%) were found to have Graves' disease. Elevated free T4, free T3,
      total T3 and suppressed TSH were seen in 14.8%, 3.3%, 26.4% and 33.0% of the
      remaining 182 pregnant women, respectively. Total and free beta-hCG correlated
      negatively with TSH (r = -0.30, P < 0.0001 and r = -0.29, P < 0.0001,
      respectively), positively with fT4 (r = 0.283, P < 0.001 and r = 0.253, P <
      0.001) and fT3 (r = 0.273, P < 0.001 and r = 0.204, P < 0.01). 11.0% of cases had
      gestational thyrotoxicosis (GT) defined as elevated free T4 (> 19.1 pmol/l),
      suppressed TSH (< 0.36 mIU/l) and TRAb levels within the reference interval (0
      0.9 U/l). The prevalence of GT was significantly higher in patients tested at 8
      11 weeks compared to those evaluated at 12-14 weeks (14.4% vs. 4.7%, P < 0.05).
      Total beta-hCG (P = 0.0002), free beta-hCG (P < 0.0001) and free T4 (P = 0.02)
      levels were higher and TSH levels (P = 0.01) lower in patients tested at 8-11
      weeks. Significant positive correlations between both total and free beta-hCG
      with free T4 were seen at 8-11 weeks but not in patients tested at 12 weeks or
      later. TT3 levels were similar in the two groups. CONCLUSIONS: Using sensitive
      assays, the prevalence of gestational thyrotoxicosis in Asian women was found to
      be 11.0% and was significantly higher in subjects at 8-11 weeks of gestation than
      at 12-14 weeks. The positive correlation between hCG and free T4 seen in patients
      tested at 8-11 weeks was absent in patients tested at later stages of the first
      trimester. Future studies investigating the entity of gestational thyrotoxicosis,
      at least in Asian patients, should focus on patients at earlier stages of
      gestation than currently practised.

PMID- 11589684
TI  - Germline sequence variant S836S in the RET proto-oncogene is associated with low
      level predisposition to sporadic medullary thyroid carcinoma in the Spanish
      population.
AB  - OBJECTIVE: The molecular basis of sporadic medullary thyroid carcinoma (MTC)
      remains elusive. While germline gain-of-function mutations in the RET proto
      oncogene cause hereditary MTC, somatic activating RET mutations and loss of
      heterozygosity of markers in various chromosomal regions representing deletions
      of tumour suppressor genes, have been described in a variable number of sporadic
      MTC. A previous report suggested that the presence of a germline variant at RET
      codon 836 (S836S) was associated with the development of sporadic MTC and,
      furthermore, that the presence of S836S was highly correlated with somatic RET
      M918T mutation in the MTC. Thus, we sought to determine if the S836S variant
      would be associated with sporadic MTC from a completely different population
      base, that of Andalucia. DESIGN: This is a case-control study to determine
      whether the presence of RET germline S836S is correlated with sporadic MTC in
      Andalucia. PATIENTS: Thirty-two patients with sporadic MTC from the Andalucia
      region of Spain, serviced by our University Hospital, were ascertained throughout
      the period 1995-99. Sporadic MTC was defined as a lack of personal or family
      history suggestive of multiple endocrine neoplasia type 2 (MEN 2) and lack of
      germline RET mutations which define any MEN 2 subtype. A region and race matched
      cohort of 250 controls was also obtained. MEASUREMENTS: The frequency of the
      S836S allele was determined in cases and controls and compared using the standard
      chi-squared statistic and Fisher's exact test. RESULTS: The polymorphic allele
      frequency at codon 836 in the control population (18/500 chromosomes, 3.6%)
      differed significantly from the MTC case cohort, 9.3% of case chromosomes (six of
      64 alleles, Fisher's exact test, two-tailed, P = 0.043). CONCLUSIONS: Germline
      RET S836S variant is associated with a two- to three-fold risk of sporadic MTC in
      the Spanish population, in accordance with a previous study based on German
      cases. Our observations suggest that this phenomenon might be universal and not
      limited to Germany.

PMID- 11589685
TI  - Complete surgical lymph node resection does not prevent authentic recurrences of
      medullary thyroid carcinoma.
AB  - BACKGROUND: Medullary thyroid carcinoma is a rare tumour derived from the thyroid
      parafollicular calcitonin-secreting cells. Calcitonin is a very specific marker
      of this cancer that allows preoperative diagnosis. Serum calcitonin assay is
      particularly useful to define the postoperative state of patients (cured,
      apparently cured, not cured) and, because of its great sensitivity, it has a
      major place in the postoperative follow-up. OBJECTIVE: To identify, among
      patients thyroidectomized for medullary thyroid carcinoma (MTC), the
      characteristics of authentic recurrent MTC [re-elevation of stimulated serum
      calcitonin (CT) level measured by a sensitive immunoradiometric assay, after
      postoperative normalization]. PATIENTS AND METHODS: We first collected, through
      the national registry of the French Calcitonin Tumour Study Group (GETC),
      patients who had undergone a total thyroidectomy with or without lymph node
      surgery and who were not cured at the last follow-up visit. Among 453 such
      patients included in the database, 15 patients met the criteria for authentic
      recurrence as defined in previous studies: they had been first considered as
      cured during the 6 months following the initial surgical procedure (basal and
      pentagastrin-stimulated serum calcitonin level <or= 10 ng/l) but had a secondary
      rerise of their pentagastrin-stimulated calcitonin level, over 10 ng/l. Eight of
      them even had an undetectable (< 2 ng/l) immediate postoperative CT, confirming
      the initial postoperative cure. The characteristics (age, nature of disease,
      stage at surgery and type of node dissection) of these 15 patients were studied.
      RESULTS: According to the Tumour Node Metastasis classification, nine patients
      were T1 and, among them, five patients had had complete lymph node surgery
      without any evidence of nodal metastases (N0). The recurrence was 3.2 +/- 2.2
      years (range: 0.7-7.5) after the initial surgery. CONCLUSIONS: 3.3% of patients
      not cured at the last visit had a recurrent MTC. This recurrence occurred
      whatever the stage, and even if the primary surgery for MTC was a priori
      complete. These results emphasize the need for a regular biochemical follow-up
      because recurrence may appear many years after the initial surgery.

PMID- 11589686
TI  - Octreotide LAR treatment throughout pregnancy in an acromegalic woman.
AB  - We report a 24-year-old woman with active acromegaly despite pituitary surgery
      and irradiation who received continuous octreotide LAR treatment for the control
      of GH excess throughout her pregnancy. The patient delivered a healthy girl
      following an uneventful pregnancy. Despite a substantial materno-fetal transfer
      of octreotide, postnatal development was normal with length parameters around the
      50th percentile at 3 months of age. In almost all previously described cases (n =
      13) octreotide was stopped after the diagnosis of pregnancy was established. No
      side-effects of mother or fetus have been reported. Octreotide treatment in
      pregnancy seems to be feasible and safe. Due to the still-limited number of
      reported cases, the potential benefits of octreotide treatment should be weighed
      carefully against its possible risks.

PMID- 11589687
TI  - An immunologically anomolous parathyroid hormone variant causing
      hyperparathyroidism.

PMID- 11589688
TI  - Marimastat therapy as adjuvant to selective embolization in skeletal metastases
      of differentiated thyroid carcinoma.

PMID- 11589689
TI  - Creation of a tumour bank for post Chernobyl thyroid cancer.

PMID- 11589690
TI  - Hyperprolactinaemia induced by a nonsecreting pituitary adenoma: differential
      diagnosis with magnetization transfer MRI technique.

PMID- 11589691
TI  - The role of protein phosphorylation in human health and disease. The Sir Hans
      Krebs Medal Lecture.
AB  - The reversible phosphorylation of proteins regulates almost all aspects of cell
      life, while abnormal phosphorylation is a cause or consequence of many diseases.
      Mutations in particular protein kinases and phosphatases gives rise to a number
      of disorders and many naturally occurring toxins and pathogens exert their
      effects by altering the phosphorylation states of intracellular proteins. In this
      lecture, I present an overview of the progress that is being made in developing
      specific inhibitors of protein kinases for the treatment of cancer and chronic
      inflammatory diseases and describe how recent advances in our understanding of
      the specificity and regulation of one particular protein kinase (GSK3) may
      facilitate the development of drugs to treat diabetes that would not have the
      potential to be oncogenic. I also discuss the exploitation of specific protein
      kinase inhibitors for the study of cell signalling and make recommendations for
      their effective use in cell-based assays.

PMID- 11589692
TI  - The role of the TolC family in protein transport and multidrug efflux. From
      stereochemical certainty to mechanistic hypothesis.
AB  - Gram-negative bacteria are enveloped by a system of two membranes, and they use
      specialized multicomponent, energy-driven pumps to transport molecules directly
      across this double-layered partition from the cell interior to the extra-cellular
      environment. One component of these pumps is embedded in the outer-membrane, and
      the paradigm for its structure and function is the TolC protein from Escherichia
      coli. A common component of a wide variety of efflux pumps, TolC and its
      homologues are involved in the export of chemically diverse molecules ranging
      from large protein toxins, such as alpha-hemolysin, to small toxic compounds,
      such as antibiotics. TolC family members thus play important roles in conferring
      pathogenic bacteria with both virulence and multidrug resistance. These pumps
      assemble reversibly in a transient process that brings together TolC or its
      homologue, an inner-membrane-associated periplasmic component, an integral inner
      membrane translocase and the substrate itself. TolC can associate in this fashion
      with a variety of different partners to participate in the transport of diverse
      substrates. We review here the structure and function of TolC and the other
      components of the efflux/transport pump.

PMID- 11589693
TI  - The thermal unfolding and domain structure of Na+/K+-exchanging ATPase. A
      scanning calorimetry study.
AB  - The thermal unfolding and domain structure of Na+/K+-ATPase from pig kidney were
      studied by high-sensitivity differential scanning calorimetry (HS-DSC). The
      excess heat capacity function of Na+/K+-ATPase displays the unfolding of three
      cooperative domains with midpoint transition temperatures (Td) of 320.6, 327.5,
      331.5 K, respectively. The domain with Td = 327.5 K was identified as
      corresponding to the beta subunit, while two other domains belong to the alpha
      subunit. The thermal unfolding of the low-temperature domain leads to large
      changes in the amplitude of the short-circuit current, but has no effect on the
      ATP hydrolysing activity. Furthermore, dithiothreitol or 2-mercaptoethanol
      treatment causes destruction of this domain, accompanied by significant
      disruption of the ion transporting function and a 25% loss of ATPase activity.
      The observed total unfolding enthalpy of the protein is rather low (approximately
      12 J.g-1), suggesting that thermal denaturation of Na+/K+-ATPase does not lead to
      complete unfolding of the entire molecule. Presumably, transmembrane segments
      retain most of their secondary structure upon thermal denaturation. The binding
      of physiological ligands results in a pronounced increase in the conformational
      stability of both enzyme subunits.

PMID- 11589694
TI  - Cloning, expression, purification and characterization of patatin, a novel
      phospholipase A.
AB  - Patatin is the major protein constituent of potato tubers and displays broad
      esterase activity. The native enzyme actually belongs to a highly homologous
      multigene family of vacuolar glycoproteins. From these, the patB2 patatin gene
      was selected and cloned into pUC19 without its signal sequence but with an N
      terminal histidine-tag. This patatin was overexpressed under the control of the
      lac promotor in Escherichia coli strain DH5alpha. The protein was recovered as
      inclusion bodies, folded into its native state by solubilization in urea and
      purified to homogeneity. Starting with one gram of inclusion bodies, 19 mg of
      pure and active recombinant patatin was isolated, with even higher specific
      activity than the glycosylated wild-type patatin purified from potato tubers. The
      purified enzyme showed esterolytic activity with p-nitrophenylesters dissolved in
      Triton X-100 micelles. The activity of patatin on p-nitrophenylesters with
      different carbon chain lengths showed an optimum for p-nitrophenylesters with 10
      carbon atoms. Besides general esterolytic activity, the pure enzyme was found to
      display high phospholipase A activity in particular with the substrates 1,2
      dioctanoyl-sn-glycero-3-phosphocholine (diC(8)PCho) (127 U.mg(-1)) and 1,2
      dinonanoyl-sn-glycero-3-phosphocholine (diC(9)PCho) (109 U.mg(-1)). Recently, the
      structure of human cytosolic PLA(2) (cPLA(2)) was solved, showing a novel Ser-Asp
      active site dyad [1]. Based on a partial sequence alignment of patatin with human
      cPLA(2), we propose that patatin contains a similar active site dyad. To verify
      this assumption, conserved Ser, Asp and His residues in the family of patatins
      have been modified in patatin B2. Identification of active site residues was
      based on the observation of correctly folded but inactive variants. This led to
      the assignment of Ser54 and Asp192 as the active site serine and aspartate
      residues in patatin B2, respectively.

PMID- 11589695
TI  - Distribution of alcohol dehydrogenase mRNA in the rat central nervous system.
      Consequences for brain ethanol and retinoid metabolism.
AB  - The localization of alcohol dehydrogenase (ADH) in brain regions would
      demonstrate active ethanol metabolism in brain during alcohol consumption, which
      would be a new basis to explain the effects of ethanol in the central nervous
      system. Tissue sections from several regions of adult rat brain were examined by
      in situ hybridization to detect the expression of genes encoding ADH1 and ADH4,
      enzymes highly active with ethanol and retinol. ADH1 mRNA was found in the
      granular and Purkinje cell layers of cerebellum, in the pyramidal and granule
      cells of the hippocampal formation and in some cell types of cerebral cortex.
      ADH4 expression was detected in the Purkinje cells, in the pyramidal and granule
      cells of the hippocampal formation and in the pyramidal cells of cerebral cortex.
      High levels of ADH1 and ADH4 mRNAs were detected in the CNS epithelial and
      vascular tissues: leptomeninges, choroid plexus, ependymocytes of ventricle
      walls, and endothelium of brain vessels. Histochemical methods detected ADH
      activity in rodent cerebellar slices, while Western-blot analysis showed ADH4
      protein in homogenates from several brain regions. In consequence, small but
      significant levels of ethanol metabolism can take place in distinct areas of the
      CNS following alcohol consumption, which could be related to brain damage caused
      by a local accumulation of acetaldehyde. Moreover, the involvement of ADH in the
      synthesis of retinoic acid suggests a role for the enzyme in the regulation of
      adult brain functions. The impairment of retinol oxidation by competitive
      inhibition of ADH in the presence of ethanol may be an additional origin of CNS
      abnormalities caused by ethanol.

PMID- 11589696
TI  - Participation of acetaldehyde dehydrogenases in ethanol and pyruvate metabolism
      of the yeast Saccharomyces cerevisiae.
AB  - This work was undertaken to clarify the role of acetaldehyde dehydrogenases in
      Saccharomyces cerevisiae metabolism during growth on respiratory substrates.
      Until now, there has been little agreement concerning the ability of mutants
      deleted in gene ALD4, encoding mitochondrial acetaldehyde dehydrogenase, to grow
      on ethanol. Therefore we constructed mutants in two parental strains (YPH499 and
      W303-1a). Some differences appeared in the growth characteristics of mutants
      obtained from these two parental strains. For these experiments we used ethanol,
      pyruvate or lactate as substrates. Mitochondria can oxidize lactate into pyruvate
      using an ATP synthesis-coupled pathway. The ald4Delta mutant derived from the
      YPH499 strain failed to grow on ethanol, but growth was possible for the
      ald4Delta mutant derived from the W303-1a strain. The co-disruption of ALD4 and
      PDA1 (encoding subunit E1alpha of pyruvate dehydrogenase) prevented the growth on
      pyruvate for both strains but prevented growth on lactate only in the double
      mutant derived from the YPH499 strain, indicating that the mutation effects are
      strain-dependent. To understand these differences, we measured the enzyme content
      of these different strains. We found the following: (a) the activity of cytosolic
      acetaldehyde dehydrogenase in YPH499 was relatively low compared to the W303-1a
      strain; (b) it was possible to restore the growth of the mutant derived from
      YPH499 either by addition of acetate in the media or by introduction into this
      mutant of a multicopy plasmid carrying the ALD6 gene encoding cytosolic
      acetaldehyde dehydrogenase. Therefore, the lack of growth of the mutant derived
      from the YPH499 strain seemed to be related to the low activity of acetaldehyde
      oxidation. Therefore, when cultured on ethanol, the cytosolic acetaldehyde
      dehydrogenase can partially compensate for the lack of mitochondrial acetaldehyde
      dehydrogenase only when the activity of the cytosolic enzyme is sufficient.
      However, when cultured on pyruvate and in the absence of pyruvate dehydrogenase,
      the cytosolic acetaldehyde dehydrogenase cannot compensate for the lack of the
      mitochondrial enzyme because the mitochondrial form produces intramitochondrial
      NADH and consequently ATP through oxidative phosphorylation.

PMID- 11589697
TI  - Identification of novel splice variants of the human catalytic subunit Cbeta of
      cAMP-dependent protein kinase.
AB  - Four different isoforms of the catalytic subunit of cAMP-dependent protein
      kinase, termed Calpha, Cbeta, Cgamma and PrKX have been identified. Here we
      demonstrate that the human Cbeta gene encodes six splice variants, designated
      Cbeta1, Cbeta2, Cbeta3, Cbeta4, Cbeta4ab and Cbeta4abc. The Cbeta splice variants
      differ in their N-terminal ends due to differential splicing of four different
      forms of exon 1 designated exon 1-1, 1-2, 1-3, 1-4 and three exons designated a,
      b and c. All these exons are located upstream of exon 2 in the Cbeta gene. The
      previously identified human Cbeta variant has been termed Cbeta1, and is similar
      to the Cbeta isoform identified in the mouse, ox, pig and several other mammals.
      Human Cbeta2, which is the homologue of bovine Cbeta2, has no homologue in the
      mouse. Human Cbeta3 and Cbeta4 are homologous to the murine Cbeta3 and Cbeta2
      splice variants, whereas human Cbeta4ab and Cbeta4abc represent novel isofoms
      previously not identified in any other species. At the mRNA level, the Cbeta
      splice variants reveal tissue specific expression. Cbeta1 was most abundantly
      expressed in the brain, with low-level expression in several other tissues. The
      Cbeta3 and Cbeta4 splice variants were uniquely expressed in human brain in
      contrast to Cbeta2, which was most abundantly expressed in tissues of the immune
      system, with no detectable expression in brain. We suggest that the various Cbeta
      splice variants when complexed with regulatory subunits may give rise to novel
      holoenzymes of protein kinase A that may be important for mediating specific
      effects of cAMP.

PMID- 11589698
TI  - Engineering the properties of a cold active enzyme through rational redesign of
      the active site.
AB  - In an effort to explore the effects of local flexibility on the cold adaptation
      of enzymes, we designed point mutations aiming to modify side-chain flexibility
      at the active site of the psychrophilic alkaline phosphatase from the Antarctic
      strain TAB5. The mutagenesis targets were residues Trp260 and Ala219 of the
      catalytic site and His135 of the Mg2+ binding site. The replacement of Trp260 by
      Lys in mutant W260K, resulted in an enzyme less active than the wild-type in the
      temperature range 5-25 degrees C. The additional replacement of Ala219 by Asn in
      the double mutant W260K/A219N, resulted in a drastic increase in the energy of
      activation, which was reflected in a considerably decreased activity at
      temperatures of 5-15 degrees C and a significantly increased activity at 20-25
      degrees C. Further substitution of His135 by Asp in the triple mutant
      W260K/A219N/H135D restored a low energy of activation. In addition, the His135-
      >Asp replacement in mutants H135D and W260K/A219N/H135D resulted in considerable
      stabilization. These results suggest that the psychrophilic character of mutants
      can be established or masked by very slight variations of the wild-type sequence,
      which may affect active site flexibility through changes in various
      conformational constraints.

PMID- 11589699
TI  - Molecular characterization of a phosphatidylcholine-hydrolyzing phospholipase C.
AB  - While searching for a phospholipase C (PLC) specific for phosphatidylcholine in
      mammalian tissues, we came across such an activity originating from a
      contamination of Pseudomonas fluorescens. This psychrophilic bacterium was found
      to contaminate placental extracts upon processing in the cold. The secreted
      phosphatidylcholine-hydrolyzing PLC was purified by a combination of
      chromatographic procedures. As substrates, the enzyme preferred dipalmitoyl
      phosphatidylcholine and 1-palmitoyl-2-arachidonoyl-phosphatidylcholine over
      phosphatidylinositol. The active enzyme is a monomer of approximately 40 kDa. As
      for other bacterial PLCs, the enzyme requires Ca2+ and Zn2+ for activity;
      dithiothreitol affected the activity due to its chelation of Zn2+, but this
      inhibition could be compensated for by addition of ZnCl2. The compound D609,
      described to selectively inhibit phosphatidylcholine-specific PLCs, caused half
      inhibition of the P. fluorescens enzyme at approximately 420 microM, while 50
      fold lower concentrations similarly affected PLCs from Bacillus cereus and
      Clostridium perfringens. Partial peptide sequences obtained from the pure P.
      fluorescens enzyme after tryptic cleavage were used to clone a DNA fragment of
      3.5 kb from a P. fluorescens gene library prepared from our laboratory isolate.
      It contains an ORF of 1155 nucleotides encoding the PLC. There is no significant
      sequence homology to other PLCs, suggesting that the P. fluorescens enzyme
      represents a distinct subclass of bacterial PLCs. The protein lacks cysteine
      residues and consequently contains no disulfide bonds. Interestingly, P.
      fluorescens reference strain DSMZ 50090 is devoid of the PLC activity described
      here as well as of the relevant coding sequence.

PMID- 11589700
TI  - Structural investigation on the lipooligosaccharide fraction of psychrophilic
      Pseudoalteromonas haloplanktis TAC 125 bacterium.
AB  - The core structure of the cell-wall lipooligosaccharide (LOS) fraction of an
      Antarctic Gram-negative bacterium, Pseudoalteromonas haloplanktis TAC 125 strain,
      was determined to be deacetylated alditols. These were obtained from native LOS
      fraction by O-deacylation, dephosphorylation, reduction and finally N
      deacylation. Two novel structures were detected, the more highly represented
      molecule consisting of the following hexasaccharide chain: alpha-D-ManpNH(2)-(1-
      >3)-beta-D-Galp-(1-->4)-alpha-L-glycero-D-manno-Hepp-(1-->5)-alpha-D-Kdo-(2-->6)
      beta-D-GlcpNH(2)-(1-->6)-D-GlcNH(2)(ol) while the corresponding pentasaccharide,
      lacking the ManpNH(2) residue, was less abundant. To the best of our knowledge,
      the structural investigation presented here, mainly performed by NMR and MS
      methods, is the first report of the lipopolysaccharide fraction of a
      psychrophilic bacterium.

PMID- 11589701
TI  - Structural studies of a cell wall polysaccharide of Trichosporon asahii
      containing antigen II.
AB  - The structure of a cell-wall polysaccharide containing antigen II from
      Trichosporon asahii was investigated. A purified glucuronoxylomannan (GXM)
      antigen was found to contain O-acetyl groups that contribute to the serological
      reactivity. The structure of GXM was analyzed by partial acid hydrolysis,
      methylation analysis, controlled Smith degradation, NMR studies, and fluorophore
      assisted carbohydrate electrophoresis. GXM has an alpha-(1-->3)-D-mannan backbone
      with a beta-D-glucopyranosyluronic acid residue bound to O-2 of a mannopyranosyl
      residue and the same number of beta-D-xylopyranosyl residues as mannose. Side
      chains of beta-D-xylopyranosyl-D-xylopyranose, forming a nonreducing terminus,
      and beta-D-xylopyranosyl residues were attached to O-2, O-4, and O-6 of the
      mannose residues.

PMID- 11589702
TI  - Role of loops in the folding and stability of yeast phosphoglycerate kinase.
AB  - Yeast phosphoglycerate kinase (yPGK) is a monomeric two domain protein used as
      folding model representative of large proteins. We inserted short unstructured
      sequences (four Gly or four Thr) into the connections between secondary structure
      elements and studied the consequences of these insertions on the folding process
      and stability of yPGK. All the mutated proteins can refold efficiently. The
      effect per residue on stability is larger for the first inserted residue.
      Insertion in two long betaalpha loops (at residue positions 71 and 129) is more
      destabilizing than an insertion in a short alphabeta loop (at residue position
      89) located on the opposite side of the N-terminal domain. The effect on
      stability is mainly due to a large increase of the unfolding rate rather than a
      decrease of the folding rate. This suggests that these connections between
      secondary structure elements do not play an active role in directing the folding
      process. Insertion into the short alphabeta loop (position 89) has limited
      effects on stability and results in the detection of a kinetic phase not
      previously seen with the wild-type protein, suggesting that insertions in this
      particular loop do qualitatively affect the folding process without a large
      effect on folding efficiency. For the two long betaalpha loops (positions 71 and
      129) located in the inner surface of the N-terminal domain, the effects on
      stability are possibly associated with decoupling of the two domains as observed
      by differential scanning calorimetry during thermal unfolding.

PMID- 11589703
TI  - Recombinant domains of mouse nidogen-1 and their binding to basement membrane
      proteins and monoclonal antibodies.
AB  - The basement membrane protein, nidogen-1, was previously shown to consist of
      three globular domains, G1 to G3, and two connecting segments. Nidogen-1 is a
      major mediator in the formation of ternary complexes with laminins, collagen IV,
      perlecan and fibulins. In the present study, we have produced recombinant
      proteins of these predicted domains in mammalian cells and used these proteins
      for crystallographic and binding epitope analyses. These fragments included G1,
      G2, the rod domain and a slightly larger G3 structure; all were obtained in good
      yields and were shown to be properly folded using electron microscopy. Surface
      plasmon resonance assays demonstrated high affinity binding (Kd = 3-9 nM) of
      domain G2 for collagen IV, perlecan domain IV-1 and fibulin-2, and a more
      moderate Kd for fibulin-1C. Domain G3 contained high affinity binding sites for
      the laminin gamma1 chain and collagen IV (Kd = 1 nM) and weaker binding sites for
      fibulin-1C and fibulin-2. A moderate binding affinity was also observed between
      domain G1 and fibulin-2, while no activity could be detected for the nidogen rod
      domain. Together, these data indicate the potential of nidogen-1 for multiple
      interactions within basement membranes. A similar binding repertoire was also
      identified for seven rat monoclonal antibodies that bound with Kd = 2-30 nM to
      either G1, G1-G2, G2, the rod domain or G3. Three of the antibodies showed
      strongly reduced binding to G2 and G3 after complex formation with either a
      perlecan domain or laminin-1.

PMID- 11589704
TI  - Isolation and characterization of photosystem II subcomplexes from cyanobacteria
      lacking photosystem I.
AB  - A photosystem II (PSII) core complex lacking the internal antenna CP43 protein
      was isolated from the photosystem II of Synechocystis PCC6803, which lacks
      photosystem I (PSI). CP47-RC and reaction centre (RCII) complexes were also
      obtained in a single procedure by direct solubilization of whole thylakoid
      membranes. The CP47-RC subcore complex was characterized by SDS/PAGE,
      immunoblotting, MALDI MS, visible and fluorescence spectroscopy, and absorption
      detected magnetic resonance. The purity and functionality of RCII was also
      assayed. These preparations may be useful for mutational analysis of PSII RC and
      CP47-RC in studying primary reactions of oxygenic photosynthesis.

PMID- 11589705
TI  - Structural modifications in the membrane-bound regions of the gastric H+/K+
      ATPase upon ligand binding.
AB  - Extensive trypsin proteolysis was used to examine the accessibility of membrane
      bound segments of the gastric H+/K+-ATPase under different experimental
      conditions known to induce either the E1 or the E2 conformation. Membrane
      anchored peptides were isolated after trypsinolysis and identified by sequencing.
      We show that several membrane bound segments are involved in the conformational
      change. In the N-terminal region, a M1-M2 peptide (12 kDa) was found to be
      associated with the membrane fraction after digestion in the presence of K+ or in
      the presence of vanadate (12 kDa and 15 kDa). In the M3 and M4 region, no
      difference was observed for the peptide obtained in E1 or E2-K conformations, but
      the peptide generated in the presence of vanadate begins 12 amino-acid residues
      earlier in the sequence. Cytoplasmic loop region: we show here that a peptide
      beginning at Asp574 and predicted to end at Arg693 is associated with the
      membrane for a vanadate-induced conformation. In the M5-M6 region, the membrane
      anchored peptide obtained on E1 is 39 amino acids shorter than the E2 peptide. In
      the M7-M8 region, the same peptide encompassing the M7 and M8 transmembrane
      segments was produced for E1 and E2 conformations.

PMID- 11589706
TI  - Redox properties of the couple compound I/native enzyme of myeloperoxidase and
      eosinophil peroxidase.
AB  - The standard reduction potential of the redox couple compound I/native enzyme has
      been determined for human myeloperoxidase (MPO) and eosinophil peroxidase (EPO)
      at pH 7.0 and 25 degrees C. This was achieved by rapid mixing of peroxidases with
      either hydrogen peroxide or hypochlorous acid and measuring
      spectrophotometrically concentrations of the reacting species and products at
      equilibrium. By using hydrogen peroxide, the standard reduction potential at pH
      7.0 and 25 degrees C was 1.16 +/- 0.01 V for MPO and 1.10 +/- 0.01 V for EPO,
      independently of the concentration of hydrogen peroxide and peroxidases. In the
      case of hypochlorous acid, standard reduction potentials were dependent on the
      hypochlorous acid concentration used. They ranged from 1.16 V at low hypochlorous
      acid to 1.09 V at higher hypochlorous acid for MPO and from 1.10 V to 1.03 V for
      EPO. Thus, consistent results for the standard reduction potentials of redox
      couple compound I/native enzyme of both peroxidases were obtained with all
      hydrogen peroxide and at low hypochlorous acid concentrations: possible reasons
      for the deviation at higher concentrations of hypochlorous acid are discussed.
      They include instability of hypochlorous acid, reactions of hypochlorous acid
      with different amino-acid side chains in peroxidases as well as the appearance of
      a compound I-chloride complex.

PMID- 11589707
TI  - Heterologous expression and characterization of the exopolysaccharide from
      Streptococcus thermophilus Sfi39.
AB  - The genes responsible for exopolysaccharide (EPS) synthesis in Streptococcus
      thermophilus Sfi39 were identified on a 20-kb genomic fragment. The two genes,
      epsE and epsG, were shown to be involved in EPS synthesis as their disruption
      lead to the loss of the ropy phenotype. Several naturally selected nonropy
      mutants were isolated, one acquired an insertion sequence (IS)-element (IS905) in
      the middle of the eps gene cluster. The eps gene cluster was cloned and
      transferred into a nonEPS-producing heterologous host, Lactococcus lactis MG1363.
      The EPS produced was shown by chemical analysis and NMR spectroscopy to be
      identical to the EPS produced by S. thermophilus Sfi39. This demonstrated first
      that all genes needed for EPS production and export were present in the S.
      thermophilus Sfi39 eps gene cluster, and second that the heterologous production
      of an EPS was possible by transfer of the complete eps gene cluster alone,
      provided that the heterologous host possessed all necessary genetic information
      for precursor synthesis.

PMID- 11589708
TI  - Cloning and expression of a membrane-bound CMP-N-acetylneuraminic acid
      hydroxylase from the starfish Asterias rubens.
AB  - The sialic acid N-glycolylneuraminic acid (Neu5Gc) is synthesized by the action
      of CMP-Neu5Ac hydroxylase. The enzyme from various mammals has been purified,
      characterized and sequenced by cDNA cloning. Although functional sequence motifs
      can be postulated from comparisons with several enzymes, no global homologies to
      any other proteins have been found. The unusual characteristics of this
      hydroxylase raise questions about its evolution. As echinoderms are
      phylogenetically the oldest organisms possessing Neu5Gc, they represent a
      starting point for investigations on the origin of this enzyme. Despite many
      similarities with its mammalian counterpart, CMP-Neu5Ac hydroxylase from the
      starfish A. rubens exhibits fundamental differences, most notably its association
      with a membrane and a requirement for high ionic strength. In order to shed light
      on the structural basis for these differences, the primary structure of CMP
      Neu5Ac hydroxylase from A. rubens has been determined by PCR and cDNA-cloning
      techniques, using initial sequence information from the mouse enzyme. The
      complete assembled cDNA contained an ORF coding for a protein of 653 amino acids
      with a molecular mass of 75 kDa. The deduced amino-acid sequence exhibited a high
      degree of homology with the mammalian enzyme, although the C-terminus was some 60
      residues longer. This extension consists of a terminal hydrophobic region, which
      may mediate membrane-binding, and a preceding hydrophilic sequence which probably
      serves as a hinge or linker. The identity of the ORF was confirmed by expression
      of active CMP-Neu5Ac hydroxylase in E. coli at low temperatures.

PMID- 11589709
TI  - B"-associated factor(s) involved in RNA polymerase III preinitiation complex
      formation and start-site selection.
AB  - The TFIIIB transcription factor is the central component of the RNA polymerase
      III transcriptional machinery. In yeast, this factor is composed of three
      essential polypeptides TBP, TFIIIB70 and TFIIIB90, that are sufficient as
      recombinant proteins, together with TFIIIC, to promote accurate transcription in
      vitro. Here we show that a partially purified fraction, named B", that contains
      the TFIIIB90 subunit, displays properties distinct from recombinant TFIIIB90.
      This fraction contains at least a component that interacts with DNA*TFIIIC
      complexes, either alone or in combination with TFIIIB90, and increases the
      resistance of the complexes to heparin treatment. In addition, primer extension
      and single round transcriptions experiment reveal a different start-site
      selection pattern directed by B" or rTFIIIB90. In mixing experiments, we show
      that an activity in B", distinct from TFIIIB90, can promote transcription
      initiation at the +1 site without affecting the rate of preinitiation complex
      formation. Our data suggest the existence of at least one new component that
      participates in preinitiation complex formation and influences start-site
      selection by RNA polymerase III.

PMID- 11589710
TI  - Identification of coenzyme M biosynthetic 2-phosphosulfolactate phosphatase. A
      member of a new class of Mg(2+)-dependent acid phosphatases.
AB  - Coenzyme M (CoM; 2-mercaptoethanesulfonic acid) is the terminal methyl carrier in
      methanogenesis. Methanogenic archaea begin the production of this essential
      cofactor by sulfonating phosphoenolpyruvate to form 2-phospho-3-sulfolactate.
      After dephosphorylation, this precursor is oxidized, decarboxylated and then
      reductively thiolated to form CoM. A thermostable phosphosulfolactate
      phosphohydrolase (EC 3.1.3.-) catalyzing the second step in CoM biosynthesis, was
      identified in the hyperthermophilic euryarchaeon Methanococcus jannaschii. The
      predicted ORF MJ1140 in the genome of M. jannaschii encodes ComB, a Mg2+
      dependent acid phosphatase that is specific for 2-hydroxycarboxylic acid
      phosphate esters. Recombinantly expressed purified ComB efficiently hydrolyzes
      rac-2-phosphosulfolactate, (S)-2-phospholactate, phosphoglycolate and both
      enantiomers of 2-phosphomalate. In contrast to previously studied
      phosphoglycolate phosphatases, ComB has a low pH optimum for activity, a narrow
      substrate specificity and an amino acid sequence dissimilar to any biochemically
      characterized protein. Like other phosphatases that function via covalent
      phosphoenzyme intermediates, ComB can catalyze a transphosphorylation reaction.
      Homologs of comB are identified in all available cyanobacterial genome sequences
      and in genomes from phylogenetically diverse bacteria and archaea; most of these
      organisms lack homologs of other CoM biosynthetic genes. The broad and disparate
      distribution of comB homologs suggests that the gene has been recruited
      frequently into new metabolic pathways.

PMID- 11589712
TI  - NADPH oxidase of Epstein-Barr-virus immortalized B lymphocytes. Effect of
      cytochrome b(558) glycosylation.
AB  - The phagocyte NADPH oxidase is known to be expressed in Epstein-Barr virus (EBV)
      immortalized B lymphocytes. But even if its molecular composition and its
      catalytic mechanisms are similar, the activity measured in B cells is very low
      compared to that of neutrophils. This could be explained by the low expression of
      cytochrome b558, the membrane redox component, but also by a defect in the
      activation process. This work is focused on gp91-phox glycosylation in B
      lymphocytes to assess its role in the complex assembly upon activation. Atomic
      force microscopy (AFM) combined with immunochemical approaches were used to
      investigate the effect of the glycosylation on the structure of cytochrome b558
      inserted into liposomes, on the reconstituted oxidase activity in vitro, and to
      directly monitor interaction forces between specific antibodies and the
      hemoprotein in its native or deglycosylated state. The results show that in EBV-B
      cells, gp91-phox glycosylation is higher than in neutrophils. The interaction
      force measured between the monoclonal antibody 11C12, known to inhibit O(-2)
      production in B lymphocytes, and the hemoprotein is increased after
      deglycosylation. This suggested that the epitope region recognized by this
      antibody is partly hidden in B cells, and that this region could be involved in
      the conformational change that occurs in the hemoprotein during the complex
      assembly. The high glycosylation of gp91-phox in B cells associated with the
      lipidic environment could lead to additional structural constraints in the
      membrane-bound hemoprotein that partly blocked the hemoprotein in its inactive
      state.

PMID- 11589711
TI  - Structural determinants for ligand binding and catalysis of triosephosphate
      isomerase.
AB  - The crystal structure of leishmania triosephosphate isomerase (TIM) complexed
      with 2-(N-formyl-N-hydroxy)-aminoethyl phosphonate (IPP) highlights the
      importance of Asn11 for binding and catalysis. IPP is an analogue of the
      substrate D-glyceraldehyde-3-phosphate, and it is observed to bind with its
      aldehyde oxygen in an oxyanion hole formed by ND2 of Asn11 and NE2 of His95.
      Comparison of the mode of binding of IPP and the transition state analogue
      phosphoglycolohydroxamate (PGH) suggests that the Glu167 side chain, as well as
      the triose part of the substrate, adopt different conformations as the catalysed
      reaction proceeds. Comparison of the TIM-IPP and the TIM-PGH structures with
      other liganded and unliganded structures also highlights the conformational
      flexibility of the ligand and the active site, as well as the conserved mode of
      ligand binding.

PMID- 11589713
TI  - The AUG start codon of the Saccharomyces cerevisiae NFS1 gene can be substituted
      for by UUG without increased initiation of translation at downstream codons.
AB  - The selection of the site for initiation of translation for the Saccharomyces
      cerevisiae NFS1 gene was examined using mutated AUG1, AUG2 and AUG3 codons. When
      AUG1 of the yeast NFS1 gene was mutated to UUG and the resulting mRNA was
      translated in vitro using a reticulocyte system, initiation from the mutated
      codon was abolished and occurred instead at downstream codons at increased rates.
      When the same mRNA was translated using a yeast extract, translation initiated at
      the mutated codon, albeit at a reduced rate, and there was no increased
      translation at downstream AUG codons. The NFS1 gene in which AUG1 was replaced by
      UUG was also able to substitute for the wild-type gene in vivo in yeast. Western
      blots confirmed that the encoded protein was the same size as that encoded by the
      wild-type gene and that both the wild-type and mutated proteins localized to
      mitochondria. This is apparently the first example of a yeast protein where
      mutagenesis of AUG1 does not lead to alternate use of a downstream AUG.

PMID- 11589714
TI  - New antigenic regions of streptokinase are identified by affinity-directed mass
      spectrometry.
AB  - Streptokinase (SK) is a bacterial protein used for the treatment of myocardial
      infarction, which is immunogenic in humans. Here we report the use of an affinity
      directed MS approach to determine the minimal epitopes involved in the binding
      between SK and patient antibodies. Using this method we have identified two novel
      epitopes and mapped these to the minimal recognition regions formed by the amino
      acids D96-E99 and F323-D328. We have also located three previously identified
      antigenic regions and have now mapped them and shown that they can be defined
      more precisely as residues P4-L8, P171-P177 and K334-N338.

PMID- 11589715
TI  - Serum chromogranin A in the control of patients on long-term treatment with
      inhibitors of acid secretion.

PMID- 11589716
TI  - Damaged myocytes as detected by the colocalization of DNA fragmentation and
      tissue transglutaminase and their prognostic significance in enterovirus
      associated dilated cardiomyopathy.
AB  - BACKGROUND: Apoptotic cardiac myocytes have been described in chronic heart
      failure, but no data exist on the relationship between these 'damaged' myocytes
      and myocardial detection of enterovirus RNA often associated with dilated
      cardiomyopathy (DCM). DESIGN: In patients with idiopathic DCM, endomyocardial
      biopsy samples were studied for enteroviral RNA by one step reverse transcription
      polymerase chain reaction (PCR) and a subsequent hybridization of the PCR product
      using a Southern blot technique. The endomyocardial biopsies were further
      investigated for markers of cell damage and apoptosis: DNA fragmentation and
      expression of tissue-transglutaminase (TTG) in the myocytes using the in-situ
      endlabelling method or an anti-TTG-staining, respectively. To assess the
      prognostic significance of these two markers the correlation between the
      percentage of myocytes positive both for DNA fragmentation and TTG (the index of
      damaged myocytes) and the hemodynamic course of the patients during a mean follow
      up period of 15.9 +/- 6.2 months was investigated prospectively by
      echocardiography. RESULTS: In 14 (45%) of the 31 patients with idiopathic DCM,
      enteroviral RNA was found in the endomyocardial biopsy samples, while 17 patients
      (55%) were enterovirus-negative. In enterovirus-positive patients, the index of
      'damaged' myocytes was significantly lower (10.7 +/- 4.9% vs. 19.2 +/- 8.8%, P =
      0.002) and the left ventricular ejection fraction (LVEF) improved significantly
      (P = 0.00017 vs. P = 0.13) during long-term follow-up. In addition, a weak
      negative correlation was seen between the index of damaged myocytes and the
      changes in LVEF in all patients during long-term follow-up (r = - 0.48, P =
      0.004). CONCLUSION: Our results favour the view that enterovirus-positive
      patients with DCM have less damaged myocytes and a better haemodynamic course
      than enterovirus-negative patients.

PMID- 11589717
TI  - Brachial artery pulse pressure and common carotid artery diameter: mutually
      independent associations with mortality in subjects with a recent history of
      impaired glucose tolerance.
AB  - BACKGROUND: Decreased large artery function, as reflected by increased brachial
      artery pulse pressure and increased carotid artery diameter and stiffness, may
      contribute to the increased mortality risk that is observed in subjects with
      impaired glucose tolerance. We therefore investigated the association between
      brachial artery pulse pressure and carotid artery diameter and stiffness, which
      are estimates of central artery stiffness and arterial remodelling, respectively,
      and mortality in subjects with a recent history of impaired glucose tolerance.
      DESIGN: A prospective, population-based cohort study. We measured brachial artery
      pulse pressure by oscillometric blood pressure measurements, and common carotid
      artery diameter and distensibility and compliance coefficients by ultrasound in
      140 subjects with a recent history of impaired glucose tolerance. During a median
      6.6-year follow-up, 16 subjects died. RESULTS: Brachial artery pulse pressure and
      common carotid artery diameter were positively related to all-cause mortality
      [hazard ratios per standard deviation, 1.7 (1.2-2.5) and 2.1 (1.3-3.3),
      respectively]. Results were similar after adjustment for gender, age, waist-to
      hip ratio, body mass index, total cholesterol concentration, pre-existent
      cardiovascular disease, and hypertension, and after additional mutual adjustment.
      Common carotid artery distensibility and compliance coefficients were not
      statistically significantly associated with mortality. CONCLUSIONS: Among
      subjects with a recent history of impaired glucose tolerance, brachial artery
      pulse pressure and common carotid artery diameter are independently associated
      with mortality risk. Stiffness of the central arteries may explain the
      association between pulse pressure and mortality risk. The association between
      carotid diameter and mortality risk is more likely to reflect arterial
      remodelling in response to atherosclerosis than that in response to increased
      local stiffness.

PMID- 11589719
TI  - Zinc salts precipitate unconjugated bilirubin in vitro and inhibit enterohepatic
      cycling of bilirubin in hamsters.
AB  - BACKGROUND: We have evidence for enterohepatic cycling of bilirubin
      experimentally and in vivo in humans. This study was designed to investigate
      whether Zn salts might inhibit such cycling of bilirubin. MATERIALS AND METHODS:
      Micellar bile salt solutions with unconjugated bilirubin were prepared,
      appropriate concentrations of Zn salts were added, and unconjugated bilirubin
      precipitation was measured. Hamsters and Wistar rats were fed a chow diet or a
      chow diet enriched with 1% ZnSO4, and bilirubin secretion rates were monitored.
      RESULTS: Unconjugated bilirubin was precipitated maximally (90%) after a 10-min
      incubation with 5 mM Zn salts in the pH range of 6.8-9.0. In control hamsters,
      total bilirubin secretion rates into bile were 36.0 +/- 2.8 nmol h(-1) 100g(-1)
      body weight, whereas they were 25.0 +/- 3.3 nmol h-1 100(-1) g in the ZnSO4 group
      (P < 0.05). CONCLUSIONS: Zn salts that flocculate at physiological pH adsorb
      unconjugated bilirubin almost completely from unsaturated micellar BS solutions.
      In addition, Zn salts administered orally suppress biliary bilirubin secretion
      rates in hamsters. These findings suggest that the administration of Zn salts may
      inhibit the enterohepatic cycling of unconjugated bilirubin in humans who are
      predisposed to pigment gallstone formation due to diet, disease or drugs.

PMID- 11589718
TI  - Loop diuretics alter the diurnal rhythm of endogenous parathyroid hormone
      secretion. A randomized-controlled study on the effects of loop- and thiazide
      diuretics on the diurnal rhythms of calcitropic hormones and biochemical bone
      markers in postmenopausal women.
AB  - BACKGROUND: Thiazide diuretics (TD) reduce urinary calcium, bone loss and
      fracture risk. Loop diuretics (LD) may have opposite effects. These effects could
      depend on induced rhythmic changes in bone and calcium homeostasis. DESIGN: After
      a run-in period of 7 days, we studied (in a factorial design) the diurnal rhythms
      of plasma levels of calcium, phosphate, parathyroid hormone (PTH), 1,25
      dihydroxyvitamin D and osteocalcin, as well as renal excretions rates of calcium,
      phosphate, and cross-linked N-terminal telopeptide of type 1 collagen (NTx) in 50
      postmenopausal women randomized to treatment with either a thiazide diuretic (TD;
      bendroflumethiazide, n = 14), a loop diuretic (LD; bumetanide, n = 13), LD plus
      TD (bendroflumethiazide plus bumetanide, n = 11), or placebo (n = 12). RESULTS:
      In all four groups, all measured quantities showed a diurnal variation. LD caused
      a steep increase, with a subsequent decrease, in urinary calcium and plasma PTH.
      The mean 24 h plasma PTH concentration was increased (8.5 +/- 0.9 mmol L-1)
      compared with placebo (4.4 +/- 0.4 mmol L-1), whereas net 24 h renal calcium
      excretion did not differ from that of the placebo group due to a rebound
      hypocalciuria. Compared with placebo, diurnal rhythms of plasma phosphate and
      osteocalcin were changed with an increase during daytime and a decrease during
      the night. TD did not alter the diurnal rhythm of any of the measured quantities.
      However, the 24-h renal calcium excretion decreased, whereas the mean 24-h plasma
      calcium concentration increased without PTH suppression. LD plus TD caused
      changes similar to those observed with LD alone. CONCLUSION: One daily dose of LD
      increases parathyroid activity with alterations in the diurnal pattern of
      osteocalcin. This could indicate a potential anabolic effect of LD.

PMID- 11589721
TI  - Apolipoprotein E polymorphism and lithogenic factors in gallbladder bile.
AB  - BACKGROUND: Associations between the polymorphism of apolipoprotein E, which
      plays an important role in cholesterol metabolism and cholesterol gallstone
      formation, have been reported recently. Patients with the apo E4 isoform showed
      increased numbers and cholesterol contents of their stones, a higher frequency of
      cholesterol crystals in bile, increased susceptibility to gallstone fragmentation
      by extracorporeal shock-wave lithotripsy and an increase in recurrence rate after
      dissolution. A recent study, however, showed that fast cholesterol
      crystallization in bile is associated with multiple stones but not with apo E4.
      Therefore the mechanism for an increased risk of gallstone formation in patients
      with the apo E4 isoform still remains under debate. DESIGN: To clarify this issue
      we investigated 37 patients with gallstones (10 with the apo E4 allele and 27
      without the allele). Gallbladder biles were examined for total cholesterol and
      other lipids, cholesterol saturation index, crystal observation time, crystal
      mass, total protein and mucin. Moreover, number of gallstones and cholesterol in
      gallstones was compared in both groups. RESULTS: The crystal observation time
      (2.5 vs. 2.0 days, median) and the cholesterol saturation index (1.34 +/- 0.45
      vs. 1.43 +/- 0.74) did not differ significantly between the apo E4 and the non
      apo E4 group. Total biliary lipids (11.6 +/- 3.8 vs. 9.3 +/- 3.9 g 100 mL-1, P =
      0.126) and total biliary cholesterol (21.8 +/- 9.7 vs. 15.7 +/- 7 mmol L-1, P =
      0.067) tended to be elevated in the apo E4 group. Crystal mass (3.60 +/- 4.10 vs.
      2.38 +/- 2.70 mmol L-1), biliary total protein (8.6 +/- 3.5 vs. 8.3 +/- 6.6 mg mL
      1) and mucin (0.55 +/- 0.38 vs. 0.66 +/- 0.67 mg mL-1), number
      (solitary/multiple) of gallstones and cholesterol in gallstones were not
      different in both groups of patients. CONCLUSIONS: In comparison to the non apo
      E4 patients the apo E4 group showed a trend to elevated biliary cholesterol
      whereas crystal observation time, cholesterol saturation index, crystal mass,
      number of gallstones, cholesterol content of gallstones and total protein and
      mucin were not different. These findings do not suggest an association of the apo
      E isoform and the formation of cholesterol gallstones

PMID- 11589720
TI  - Prevalence and risk of gingival enlargement in patients treated with
      anticonvulsant drugs.
AB  - BACKGROUND: Predictors of gingival enlargement in patients treated with anti
      epileptics have not been previously assessed. This study was conducted to
      determine, with the aid of two indices that score vertical and horizontal
      overgrowth, the prevalence and risk factors for gingival enlargement in patients
      treated with phenytoin and other anticonvulsant drugs. MATERIALS AND METHODS: A
      cross-sectional study was conducted and data from 59 patients taking
      antiepileptics were compared with 98 controls. Gingival enlargement was evaluated
      with two indices to score vertical overgrowth [Gingival overgrowth index (GO] and
      horizontal overgrowth [Miranda-Brunet index (MB)]. Gingival index, plaque index,
      and probing depth were also evaluated. RESULTS: The prevalence of gingival
      enlargement was significantly higher (P < 0.0001) for both indices in the
      anticonvulsants treated groups than in the control group. Gingival overgrowth was
      significantly higher for both indices in the phenytoin group than in the non
      phenytoin group. Among the possible risk factors, only the gingival index showed
      a significant association with gingival enlargement. For the MB index the risk of
      gingival enlargement (odds ratio) associated to phenytoin therapy and other
      anticonvulsants therapy were 52.6 (13.5-205) and 6.6 (1.5-28.2). Gingival index
      adjusted odds ratios for the same drugs were 5.7 (1.3-24.7) and 18.1 (2-158),
      respectively. The concordance between GO and MB indices in the control group and
      in the phenytoin-group and non phenytoin-group showed a Kappa value of 0.773 and
      0.697, respectively. CONCLUSION: This study reports significant differences in
      the prevalence and severity of gingival overgrowth in two groups of patients, one
      treated with phenytoin, and another treated with other anticonvulsants. Gingival
      inflammation is a significant risk factor for gingival enlargement in these
      patients.

PMID- 11589722
TI  - Analysis of exocrine pancreatic function in cystic fibrosis: one mild CFTR
      mutation does not exclude pancreatic insufficiency.
AB  - BACKGROUND: Cystic fibrosis (CF) is the most common cause of exocrine pancreatic
      insufficiency in childhood. The aim of the present study is to evaluate the
      correlation between genotype and exocrine pancreatic insufficiency in CF
      patients. The special emphasis was put on the analysis of mild CFTR mutations.
      DESIGN: The study comprised 394 CF patients and 105 healthy subjects (HS).
      Elastase-1 concentrations were measured in all subjects. RESULTS: Severe
      pancreatic insufficiency was associated with the presence of two CFTR gene
      mutations (DeltaF508, N1303K, CFTR dele 2,3 (21kb), G542X, 1717-1G-A, R533X,
      W1282X, 621GT, 2183AAG, R560T, 2184insA and DeltaI507, G551D, 895T) and mild
      insufficiency with the presence of at least one mutation (R117H, 3171insC,
      A155P2, 138insL, 296 + 1G-A, E92GK, E217G, 2789 + 5G-A. 3849 + 1kbC-T/3849 + 1kbC
      T) genotype resulted in high elastase-1-values. However, in case of patients with
      genotype DeltaF508/3849 + 10kbC-T, 1717-1GA/3849 + 10kbC-T as well as with
      DeltaF508/R334W, both high and low elastase-1 concentrations were found. Low E1
      values were found in a patient with DeltaF508/R347P genotype. CONCLUSION:
      Patients who carry two 'severe' mutations develop pancreatic insufficiency,
      whereas those who carry at least one 'mild' usually remain pancreatic sufficient.
      However, the presence of one mild mutation does not exclude pancreatic
      insufficiency.

PMID- 11589723
TI  - Serum chromogranin A as a screening test for gastric enterochromaffin-like cell
      hyperplasia during acid-suppressive therapy.
AB  - BACKGROUND: Serum chromogranin A (CgA), a marker of neuroendocrine neoplasia,
      increases during profound gastric acid inhibition, possibly reflecting the
      trophic effect of gastrin on the enterochromaffin-like (ECL) cells. AIMS: This
      study investigated the clinical value of serum CgA as a screening test for
      gastric fundic enterochromaffin-like (ECL) cell hyperplasia during acid
      suppressive therapy. METHOD: A consecutive series of 230 dyspeptic patients
      referred for upper gastrointestinal endoscopy was investigated in a cross
      sectional design. They were 154 patients on continuous medium-term (6 weeks to
      one year) or long-term (longer than one year) acid inhibition with either proton
      pump inhibitors (PPIs, n = 117) or histamine2-receptor antagonists (H2RAs, n =
      37) for gastro-oesophageal reflux disease, and 76 nontreated subjects, with
      normal endoscopic findings (control group). Fasting blood samples were analysed
      for gastrin and CgA. Gastric biopsy specimens (oxyntic mucosa) were examined for
      histological evaluation of gastritis (Sydney classification) and of ECL cell
      hyperplasia (Solcia classification). RESULTS: Serum CgA levels correlated
      positively with serum gastrin, following a quadratic function (r = 0.78, P <
      0.0001). Elevated serum CgA values during long-term acid inhibition correlated
      with the presence and severity of fundic ECL cell hyperplasia. Multivariate
      analysis identified hypergastrinaemia (P < 0.0001), duration of acid inhibition
      (P < 0.0001), H. pylori infection (P = 0.008), ECL cell hyperplasia (P = 0.012),
      and body gland atrophy (P = 0.043) as independent predictors of elevated serum
      CgA. In subjects on long-term acid inhibition (n = 123), serum CgA was equally
      sensitive but more specific than serum gastrin for the detection of ECL cell
      hyperplasia (sensitivity, 91.3% for both; specificity, 73% vs. 43%, P < 0.0001).
      CONCLUSIONS: During long-term gastric acid inhibition, serum CgA levels reflect
      the presence and severity of fundic ECL cell hyperplasia. Serum CgA is therefore
      a useful screening test for gastric ECL cell proliferative changes within this
      context.

PMID- 11589724
TI  - CCK-B/gastrin receptors in human colorectal cancer.
AB  - BACKGROUND: Mature amidated gastrin (G17 amide) mediates its effects in the
      gastrointestinal tract by activating G protein-coupled CCK-B/gastrin receptors.
      Although trophic actions of gastrin on the gastric mucosa have been well
      established, the effect of G17 amide, progastrin and intermediates to colon
      neoplasia in humans is controversial. While epidemiological evidence from
      patients with elevated serum gastrin levels related to pernicious anaemia does
      not support an increased risk for colon cancer, a recent study suggests that
      prolonged hypergastrinaemia is associated with an increased risk for colon
      cancer. The extent to which trophic actions of gastrin in colorectal cancer are
      mediated by functional gastrin receptors remains to be defined. The aim of the
      present study was to determine CCK-B/gastrin receptor expression, structure, and
      function in 79 patients with colon cancer. MATERIALS AND METHODS: CCK-B/gastrin
      receptor cDNAs were isolated from 79 human colorectal cancer specimens and 15
      control tissues, subcloned into the eukaryotic expression vector pCR3.1 and
      subjected to DNA sequence analysis. Wild-type and mutant cDNAs were transiently
      expressed in COS-7 cells to determine ligand affinities by 125I-labelled CCK-8S
      competition binding. Activation of the MAP kinase signalling cascade by G17 amide
      was determined in transfected Colo 320 cells expressing the wild-type or mutant
      CCK-B/gastrin receptors. Clonal expansion of single cells was quantified in
      transfected Colo 320 cells. RESULTS: Gastrin mRNA is expressed in 44% of
      colorectal cancers and in 13% of control tissues. CCK-B/gastrin receptor mRNA is
      expressed in 38% of colorectal cancers and 13% of normal colonic tissue. Co
      expression of gastrin and CCK-B/gastrin receptor message is significantly
      increased in colorectal cancer specimens (32% vs. 0%). There is no correlation
      between CCK-B/gastrin receptor expression and disease stage or histological
      grading. DNA sequence analysis revealed one spontaneous CCK-B/gastrin receptor
      mutation within the third intracellular loop with an exchange of valine-287 for
      phenylalanine. Pharmacological characterisation of the 287V --> F CCK-B/gastrin
      receptor reveals wild-type affinities for G17 amide, glycine-extended gastrin,
      CCK-8S and L-365,260. Mutation 287V --> F is associated with a loss of gastrin
      induced MAPK p44/p42 signalling in Colo 320 cells while clonal expansion from
      single cells is increased by 53.1 +/- 15.9% when compared to Colo 320 cells
      expressing wild-type CCK-B/gastrin receptors. CONCLUSIONS: Structural alterations
      of CCK-B/gastrin receptors may account for increased growth-promoting effects of
      amidated gastrins in colorectal cancer.

PMID- 11589725
TI  - Fcgamma receptors in autoimmune diseases.
AB  - Fcgamma-receptors (Fcgamma-R) recognise the Fc portion of IgG and thus form a
      link between humoral and cellular immunity. These receptors are expressed by a
      variety of immune cells, and they function in the binding of immune complexes or
      IgG-opsonised particles, such as microbial pathogens. The are three major types
      of Fcgamma-R, namely Fcgamma-RI (CD64), Fcgamma-RII (CD32) and Fcgamma-RIII
      (CD16), and these differ in their ability to bind IgG and complexes. There are
      many isoforms of these receptors and a number of recently identified
      polymorphisms in their structure. This review describes the structure and
      function of these Fcgamma-Rs, and highlights how gene deficiencies and
      polymorphisms may contribute to the pathology of human diseases.

PMID- 11589726
TI  - The nude gene and the skin.
AB  - The nude mutation has been known for a long time. Nevertheless, the gene
      responsible for the defect has been identified only recently. It encodes a
      transcriptional activator of the family of forkhead proteins mainly expressed in
      thymic epithelium and distinct keratinocyte populations in the epidermis and hair
      follicles. The present review focuses on the molecular and functional
      characterization of the nude gene and its product and gives an overview as to its
      role in skin biology and the first identified target genes in the skin. In
      addition, evolutionary aspects are highlighted stressing the importance of such
      investigations for a comprehensive understanding of the nude gene product and the
      regulation of its expression. Furthermore, these studies give a hint as to when
      the nude gene has occurred first and how it has developed in molecular and
      functional terms since then.

PMID- 11589727
TI  - Presence of immunoreactive beta-endorphin in human skin.
AB  - The production and its induction by ultraviolet radiation (UVR) of
      proopiomelanocortin (POMC)-derived peptides by keratinocytes has been reported,
      albeit not consistently. Recently we demonstrated that only under specific
      culturing conditions human keratinocytes are capable of producing a beta
      endorphin (betaE)-like peptide with the characteristics of beta-lipotropin
      (betaLPH). Here the presence and UV-induction of betaE-immunoreactivity (betaE
      IR) in keratinocytes in human skin in vivo was investigated. betaE-IR was
      detectable by immunohistochemistry in keratinocytes of the follicular matrix and
      to some extent in cells of sweat ducts, but was absent from epidermal
      keratinocytes. Absence of betaE-IR was confirmed by radioimmunoassay of HPLC
      fractionated extracts of normal epidermis. Repeated exposure to solar-simulated
      UVR had no effect. This investigation is the first to demonstrate the presence of
      betaE-immunoreactive material in the follicular matrix of corporal hairs and in
      duct cells of sweat glands. The possible meaning of these results is discussed.

PMID- 11589728
TI  - Human skin mast cells rapidly release preformed and newly generated TNF-alpha and
      IL-8 following stimulation with anti-IgE and other secretagogues.
AB  - Several groups have previously reported that rodent or human leukemic mast cells
      produce inflammatory cytokines such as TNF-alpha and IL-8 as well as the pro
      allergic cytokines IL-4, IL-5 and IL-13. Comparatively little is known, however,
      regarding the ability of normal human skin mast cells to secrete these factors
      following either IgE-dependent or IgE-independent modes of activation. We
      therefore investigated whether normal human skin mast cells produce these
      cytokines following stimulation by a variety of secretagogues. Enriched isolated
      skin mast cells released both TNF-alpha and IL-8 following activation with either
      anti-IgE, SCF, substance P, compound 48/80 or A23187. This release was dose- and
      time-dependent, with maximal levels being reached within 4 h of stimulation
      involving, in part, the secretion of preformed stores of both cytokines. In
      accordance with this, using lysates of highly purified (>90%) skin mast cells, we
      could demonstrate that both TNF-alpha and IL-8 mRNA and protein were present in
      both unstimulated as well as stimulated mast cells. In stark contrast to these
      results, no significant levels of either IL-4, IL-5 or IL-13 were detected,
      regardless of the secretagogue used or the period of stimulation. These results
      show that human skin mast cells are capable of rapidly secreting pro-inflammatory
      cytokines like TNF-alpha and IL-8 following IgE-dependent activation and
      stimulation by the neuropeptide substance P, SCF and the basic polypeptide
      analogue compound 48/80. In contrast to other types of human mast cells however,
      human skin mast cells were incapable of secreting IL-4, IL-5 or IL-13 in these
      settings.

PMID- 11589729
TI  - Regulation of epidermal growth factor receptor expression in human melanocytes.
AB  - The epidermal growth factor receptor (EGFR) and its ligand, transforming growth
      factor alpha (TGFalpha), are reportedly involved in autocrine growth of melanoma
      cells. The signal pathway has also been implicated in early events of
      transformation, suggesting a function for EGFR in normal cells. This study
      reports the presence of EGFR in cultured melanocytes and examines some cellular
      responses to TGFalpha. Western analysis revealed 170 kDa bands in extracts of
      cultured neonatal human melanocytes, corresponding to the receptor Mr. Protein
      expression was more pronounced in cells during active growth. EGFR were less
      evident in cultures populated predominantly by melanized cells, indicating that
      receptor expression became reduced in differentiating cells. Immunocytochemistry
      confirmed these observations and also showed that EGFR reactivity was
      predominantly localized in the cell body but absent from dendrites. Addition of
      TGFalpha to early cultures induced a rapid increase in phosphotyrosine signal of
      the 170 kDa protein. Longer treatment (24-48 h) increased the intensity of the
      EGFR signal, suggesting that receptors had been upregulated. However, inclusion
      of TGFalpha in cultures did not result in an increase in cell numbers when
      compared to controls. The observations provide evidence of the existence of a
      receptor-mediated pathway in melanocytes which has transforming potential in
      vivo.

PMID- 11589730
TI  - Shortened telomere length is demonstrated in T-cell subsets together with a
      pronounced increased telomerase activity in CD4 positive T cells from blood of
      patients with mycosis fungoides and parapsoriasis.
AB  - We have recently demonstrated that telomerase activity is increased and telomere
      length shortened in lymphocytes from peripheral blood of patients with cutaneous
      T-cell lymphoma. In order to determine which cell type has increased telomerase
      activity and shortened telomere length, CD4+, CD8+, CLA+ CD3+ and CLA- CD3+ T
      cells were isolated from peripheral blood of 25 patients, including 15 patients
      with mycosis fungoides and 10 patients with parapsoriasis. Eleven healthy
      individuals were used as controls; CD19+ B cells were separated from each
      individual as an internal control. The results showed that the increased
      telomerase activity was significantly predominating in the CD4+ T-cell subset.
      Significantly shortened telomere length was found in CD4+ and CD8+ T-cell subsets
      from the patients compared with the same cell subsets obtained from healthy
      individuals. However, no difference was observed between the subsets; CD19+ B
      cells collected from patients and healthy control individuals had similar
      telomerase activity and telomere length which was significantly different from
      the values found in T cells. The telomere length was significantly shorter in
      CLA+ CD3+ subset than in CLA- CD3+ subset. Interestingly, increased telomerase
      activity and shortened telomere length was also detected in CD4+ T cells from
      patients with parapsoriasis indicating that alteration of telomerase activity and
      telomere length in CD4+ T cells is an early event in the pathogenesis of
      cutaneous T-cell lymphoma. Thus, the results indicate that a significant high
      level of telomerase activity and shortened telomere length frequently occur in T
      cells of patients with CTCL and may reflect tumorigenesis.

PMID- 11589731
TI  - Topical synthetic inhibitor of matrix metalloproteinases delays epidermal
      regeneration of human wounds.
AB  - Matrix metalloproteinases (MMPs) degrade extracellular proteins during
      epithelialization of wounds. To evaluate the biological significance of MMPs in
      epidermal healing, the synthetic broad-spectrum MMP inhibitor GM 6001 (also
      called Galardin and Ilomastat) was applied topically to standardized human
      wounds. GM 6001 (10 microg/microl) or vehicle alone was applied every second day
      onto 4 de-roofed 6 mm suction blister wounds on the volar forearm of healthy male
      volunteers for 12 days. GM 6001 delayed healing by 2-4 days as assessed
      macroscopically and microscopically. In situ hybridization or
      immunohistochemistry showed that MMP-1 (interstitial collagenase) was present in
      and MMP-2 (gelatinase A) close to laterally migrating keratinocytes whereas MMP-9
      (gelatinase B) was seen during maturation of new epidermis. MMP-1 was
      undetectable in blister roofs (normal epidermis) and found in low levels in
      normal skin. Total MMP-1 activities increased about 100-fold in wounds,
      independent of treatment, compared to normal skin as analyzed by specific ELISA
      based activity assay. By gelatin zymography, MMP-2, but not MMP-9, was detected
      in blister roofs and wound healing was associated with increased active MMP-2 and
      latent MMP-9 levels. GM 6001 prevented activation of MMP-2 and increased latent
      MMP-9 levels. GM 6001 delayed re-appearance of laminin-5, the synthesis of which
      correlated with epidermal regeneration. Restoration of stratum corneum, measured
      indirectly by transepidermal water loss, was also impaired (P<0.05) in the GM
      6001 group. In conclusion, pharmacological MMP inhibition delayed epidermal
      regeneration in vivo, suggesting that MMPs are required to restore epidermis
      after epidermal ablation in humans.

PMID- 11589732
TI  - Neuromediators and pigmentation.

PMID- 11589734
TI  - Pharmacological modulation of skin neuromediators (PAR II).

PMID- 11589733
TI  - Neuromediators and inflammation.

PMID- 11589735
TI  - Embryogenesis of neuro-epithelial interactions.

PMID- 11589736
TI  - Neuromediators, pain and pruritus.

PMID- 11589737
TI  - Neuroimmunology.

PMID- 11589739
TI  - Stress and the skin.

PMID- 11589738
TI  - Neurophysiology of the skin--functional anatomy of the skin nervous system.

PMID- 11589740
TI  - Paraneoplastic pemphigus.

PMID- 11589741
TI  - Human papillomavirus: clinical significance and malignant potential.

PMID- 11589742
TI  - Lactate dehydrogenase isozymes in and intralesional steroid injection therapy for
      pseudocyst of the auricle.
AB  - BACKGROUND: Various treatments for pseudocyst of the auricle have been reported.
      Recently, several patients have been treated successfully with steroid
      injections. The lactate dehydrogenase (LDH) levels of cystic fluid have been
      reported to be high, and the LDH-4 and LDH-5 isozymes were found to predominate,
      although the serum LDH levels and LDH isozyme patterns were normal. OBJECTIVE: To
      find a way of preventing auricular pseudocyst recurrences after steroid injection
      therapy and to examine the relationships between recurrences and the LDH level
      and isozyme pattern of the cystic fluid. METHODS: Steroid injection therapy was
      given to nine Japanese patients with pseudocyst of the auricle at our clinic
      between 1994 and 1999. We determined the LDH level and isozyme pattern of the
      cystic fluid and sera of seven patients. RESULTS: All nine patients in this
      series were treated successfully with steroid injections, although three suffered
      recurrences. Although the serum LDH levels of seven patients were almost normal,
      their cystic fluid LDH levels were very high. LDH-4 and LDH-5 predominated in the
      cystic fluid of all seven, although their serum LDH isozyme patterns were
      virtually normal. CONCLUSIONS: Auricular pseudocyst recurrences show no
      relationship with either the LDH levels or isozyme pattern. An undiluted solution
      of steroid fluid should be used in order to prevent recurrences.

PMID- 11589743
TI  - Identification of clustered cells in human hair follicle responsible for MMP-9
      gelatinolytic activity: consequences for the regulation of hair growth.
AB  - BACKGROUND: The control of human hair follicle growth and differentiation is
      dependent upon several well-identified factors, including androgens, cytokines,
      and growth factors. In humans, alopecia androgenetica is a common aging process
      thought to be regulated through complex genetic imbalances, which also involve
      several of these crucial identified factors (and probably others not yet
      characterized), alone or in combination. Among these factors, epidermal growth
      factor (EGF), as well as pro-inflammatory cytokines, play a pivotal role, as
      evidenced by their direct inhibitory effects on hair growth both in vitro and in
      vivo. Following such treatments, the in vitro growth of hair follicles was
      rapidly arrested and deleterious modifications of hair morphology were also
      observed. AIM: Because these cytokines act, at least partly, through the
      induction of matrix metalloproteinases (MMP), and because tissue remodeling
      occurs during the hair cycle, we attempted to identify and localize MMP in the
      human pilosebaceous unit. METHOD: We used zymography to observe human hair
      follicles in culture in vitro. RESULTS: We observed that human hair follicles in
      culture in vitro mainly and almost exclusively produce MMP-2 and MMP-9
      gelatinolytic activities. Furthermore, after stimulation with EGF, tumor necrosis
      factor-alpha (TNF-alpha), or interleukin-1alpha (IL-1alpha), MMP-9 production was
      strongly increased. Using immunohistochemistry, we then precisely localized MMP-9
      in the lower part of the inner root sheath (Henle's layer) of control human
      anagen hair follicles. CONCLUSIONS: Cytokine- and EGF-induced upregulation of MMP
      9 in the lower epithelial compartment of the human hair bulb is a major mechanism
      through which hair follicle involution, observed in alopecia, may occur.

PMID- 11589745
TI  - Anhidrotic ectodermal dysplasia with eruptive vellus hair cysts.

PMID- 11589744
TI  - Personal and practice-related characteristics of a subsample of US women
      dermatologists: data from the Women Physicians' Health Study.
AB  - BACKGROUND: The number of women dermatologists has increased dramatically over
      the past few decades. Despite this, there have been few studies examining the
      personal or professional characteristics of women dermatologists practicing in
      the USA. METHODS: A representative random sample of active, part-time,
      professionally inactive, and retired US women physicians, aged 30-70 years, was
      studied; this article compares data from the 95 responding dermatologists with
      data from 4350 other respondents. RESULTS: Women dermatologists were more likely
      to be US born, white, and married to a physician than were other women
      physicians; they were similar to other women physicians in age, marital status,
      children, amount of stress at home, political self-characterization, and personal
      health behavior. Women dermatologists were more likely to be board certified and
      to practice in solo or two-person practices than were other women physicians.
      They had fewer nights on call, were less likely to state that they worked too
      much, reported less stress at work, were more satisfied with their careers, and
      reported higher household incomes. With the decided exception of skin cancer
      prevention and screening, they were unlikely to have considerable training,
      confidence, or interest in routine prevention-related screening or counseling for
      patients. CONCLUSIONS: Women dermatologists are unlikely to be part of a minority
      group, likely to be married to another physician, and likely to have a high
      household income. They report reasonable work stress and high career
      satisfaction. Given these findings, it is not surprising that only 10% would
      consider changing their specialty were they to relive their lives.

PMID- 11589746
TI  - Glomeruloid hemangioma--a specific cutaneous marker of POEMS syndrome.

PMID- 11589747
TI  - Mucor indicus necrotizing fasciitis.

PMID- 11589748
TI  - Bilateral segmental neurofibromatosis: a case report and review.

PMID- 11589749
TI  - Cutaneous cryptococcosis associated with lepromatous leprosy.

PMID- 11589750
TI  - Topical formic acid puncture technique for the treatment of common warts.
AB  - BACKGROUND: Warts are a common chronic skin disorder that can be cosmetically
      disfiguring and, depending on the location, cause inhibition of function. The
      presence of dozens of topical and systemic treatments for warts is a testament to
      the lack of a rapid, simple, uniformly effective, inexpensive, nonscarring, and
      painless treatment. AIM: The purpose of this study was to determine the efficacy
      and safety of 85% formic acid application, an inexpensive therapy, for the
      treatment of warts. METHODS: A placebo-controlled, nonrandomized, open trial was
      performed in 100 patients with common warts attending Father Muller's Medical
      College Hospital, Mangalore. Fifty patients received 85% formic acid application
      and 50 patients received placebo (water) using a topical application/needle
      puncture technique every other day. RESULTS: Ninety-two per cent of patients who
      received formic acid application showed complete disappearance of warts after a 3
      4-week treatment period, compared to 6% in the placebo group. CONCLUSIONS: The
      results show that 85% formic acid application is a safe, economical, and
      effective alternative in the treatment of common warts with few side-effects and
      good compliance. A multicenter trial is needed to examine the efficacy and safety
      of this treatment.

PMID- 11589751
TI  - "Pot-lid" technique for aesthetic removal of small lipoma on the face.
AB  - BACKGROUND: Patients presenting with an asymptomatic subcutaneous facial lipoma
      desire its removal in order to restore the contour of the face. The standard
      treatment for lipoma is excision, with the size of the incision being about one
      half of that of the tumor itself. The long linear scar resulting from simple
      excision may fail to improve the appearance of the patient. The removal of the
      lipoma through a small incision or a punch hole decreases the size of the
      resulting scar, but does not eliminate it completely. OBJECTIVE: To improve the
      aesthetic outcome of the commonly used technique for lipoma removal, known as the
      narrow hole extrusion technique (NHET), by modification. METHODS: Four patients
      (three men and one woman) with small lipomas on the face (three on the forehead
      and one on the cheek) were selected for the procedure. A 5-mm punch was inserted
      deep into the center of the lesion to create a circular hole. The punched-out
      piece of skin was kept in normal saline. The lipoma was extruded with the help of
      a hemostat and by squeezing pressure. This resulted in the formation of a
      subcutaneous cavity. After achieving hemostasis, two absorbable buried
      subcutaneous sutures were placed to create support for the graft. The punched-out
      piece of skin was then positioned to cover the defect, like a "lid on a pot" and
      dressed. RESULTS: The color and texture match of the graft with the surrounding
      skin were excellent in three of the four patients by the end of 6 months. The
      graft, which was depressed in the fourth patient, improved through spot
      dermabrasion. CONCLUSION: The proposed modification of the NHET for lipoma
      removal improves the cosmetic outcome.

PMID- 11589752
TI  - Melatonin inhibits lipid peroxidation and stimulates the antioxidant status of
      diabetic rats.
AB  - Although melatonin has been established as a free radical scavenger and
      antioxidant, its effects in diabetes have not been thoroughly investigated. The
      purpose of this study, therefore, was to investigate the effects of melatonin
      administration on lipid peroxidation and antioxidant status in streptozotocin
      (STZ)-induced diabetes in rats. Concentrations of malondialdehyde (MDA) and
      reduced glutathione (GSH) in erythrocytes and activities of superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-Px) were compared in 3 groups of 10 rats
      each [control non-diabetic rats (group I), untreated diabetic rats (group II) and
      diabetic rats treated with melatonin (group III)]. In the study groups, diabetes
      developed 3 days after intraperitoneal (i.p.) administration of a single 60-mg/kg
      dose of STZ. Thereafter, while the rats in group II received no treatment, the
      rats in group III began to receive a 10-mg/kg i.p. dose of melatonin per day.
      After 6 wk, the rats in groups II and III had significantly lower body weights
      and significantly higher blood glucose levels than the rats of group I (P<0.001
      and P<0.001, respectively). There were no significant differences in body weight
      or blood glucose levels between groups II and III. MDA levels in untreated
      diabetic rats were higher than those in control group rats and in diabetic rats
      treated with melatonin (P<0.01 and P<0.05, respectively). However, MDA levels in
      diabetic rats treated with melatonin were not different from those of the control
      group. The GSH, GSH-Px and SOD levels of untreated diabetic rats were
      significantly lower than those of the control group (P<0.02, P<0.002 and P<0.05,
      respectively). In group III, however, melatonin prevented decreases in the thiol
      antioxidant and the associated enzymes, and so these levels were not
      significantly different from those in the control group. These results confirm
      the presence of oxidative stress in STZ-induced experimental diabetes and
      indicate the beneficial free radical-scavenging and antioxidant properties of
      melatonin.

PMID- 11589753
TI  - The effects of day-time exogenous melatonin administration on cardiac autonomic
      activity.
AB  - Melatonin has a functional role in the nocturnal regulation of sleep and
      thermoregulation. In addition to its action on peripheral receptors, melatonin
      may act by altering autonomic activity. To determine the effect of melatonin on
      cardiac autonomic activity, 5 mg of melatonin or placebo was orally administered
      to 12 young subjects at 14:00 hr, in a repeated measures design. Melatonin
      decreased sleep onset latency to Stage 2 sleep by 4.92+/-1.81 min (measured by
      Multiple Sleep Latency Tests), rectal temperature by 0.19+/-0.05 degrees C, and
      increased foot temperature by 0.74+/-0.45 degrees C (all P<0.05). Melatonin
      decreased heart rate by 3.66+/-1.68 beats/min (P<0.05) and pre-ejection period
      (measure of cardiac sympathetic activity) by 16.48+/-4.28 ms (P<0.05), but had no
      effect on respiratory sinus arrhythmia (measure of cardiac parasympathetic
      activity) (P>0.05). As the decrease in pre-ejection period is likely to have
      resulted from a decrease in blood pressure, these results do not confirm an
      effect of melatonin on cardiac sympathetic activity. However, the results do
      clearly indicate that melatonin is unlikely to drive the previously observed
      presleep increase in cardiac parasympathetic activity.

PMID- 11589754
TI  - Effects of melatonin on doxorubicin cytotoxicity in sensitive and pleiotropically
      resistant tumor cells.
AB  - Melatonin has been reported to attenuate the oxidative damage caused by
      doxorubicin on kidney, brain, heart and bone marrow, whereas the in vivo
      antitumor effects of doxorubicin were not attenuated. The effects of melatonin on
      doxorubicin cytotoxicity have, therefore, been examined on human normal mammary
      epithelium HBL-100, on mammary adenocarcinoma MCF-7, on colon carcinoma LoVo, and
      on mouse P388 leukemia cell lines, and on tumor cell sublines pleiotropically
      resistant to anthracyclines. Melatonin in the concentration range 10-2000 pg/mL
      causes an inhibition of the growth of the human cell lines examined which is not
      clearly dose-dependent and less than 25% when significant. Melatonin similarly
      causes minor effects on doxorubicin cytotoxicity either on the parental human
      cell lines or on their resistant sublines. On the contrary, 200-1000 pg/mL
      melatonin cause a significant and dose-dependent partial sensitization to
      doxorubicin of resistant P388 mouse leukemia (P388/ADR), which occurs also in
      vivo, as indicated by a significant increase in survival time of the hosts.
      Doxorubicin intracellular concentrations in P388/ADR cells are increased by
      melatonin, suggesting that melatonin might inhibit P-glycoprotein-mediated
      doxorubicin efflux from the cells. These results indicate that the use of
      melatonin in clinical cancer treatment should not pose the risk of an attenuation
      of the effectiveness of doxorubicin, and encourage the further examination of the
      possible reduction by melatonin of the host toxicity of antitumor chemotherapy.

PMID- 11589755
TI  - Rejuvenation of degenerative thymus by oral melatonin administration and the
      antagonistic action of melatonin against hydroxyl radical-induced apoptosis of
      cultured thymocytes in mice.
AB  - The effect of melatonin on age-related thymic involution and apoptosis induced by
      hydroxyl radicals (*OH) in mouse thymocyte cultures was investigated. Exogenous
      melatonin was administered in the drinking water (15 microg/mL) of 7-month-old
      male Balb/c mice for 40 consecutive days. Our results show that melatonin
      distinctly reversed the age-related thymic involution as revealed by the notable
      increase of cellular density, particularly the number of thymocytes, percentage
      of thymocytes at G2+S phases and the younger morphological appearance as a whole
      when compared with control animals. More strikingly, the recovery of these
      morphometric parameters were maintained for 30 days after the termination of
      melatonin administration suggesting that the re-established homeostasis by
      melatonin may last for a longer time. At the same time, when primary culture of
      thymocytes was preincubated with 200 microM melatonin before their exposure to
      hydroxyl radicals (*OH) generated by Fe(2+)-mediated Fenton reaction, apoptotic
      cell death induced by *OH was almost completely prevented as determined by both
      flow cytometric analysis and the TUNEL assay. DNA laddering assay also documented
      the inhibition of thymocyte apoptosis by melatonin. Furthermore, we found that
      the *OH-induced increment of caspase-3 activity in thymocytes was completely
      abolished by melatonin preincubation. Taken together, our study indicates that in
      addition to other mechanisms, melatonin may also directly act as an antioxidant
      via attenuating apoptotic thymocyte death caused by free radicals and stimulates
      thymocyte proliferation in thymus and thus to rejuvenate the degenerative organ.

PMID- 11589756
TI  - Clearance of melatonin and 6-sulfatoxymelatonin by hemodialysis in patients with
      end-stage renal disease.
AB  - Patients with end-stage renal disease (ESRD) suffer from a number of related
      disorders. These include endocrine abnormalities, sleep disturbances, and
      depression. Melatonin is involved in the synchronization of exogenous zeitgebers
      with the endogenous rhythms, and it has effects on various psychological factors.
      As the concentrations of melatonin and the effects of dialysis have only
      occasionally been investigated in ESRD, we performed a study involving 35
      patients, measuring the serum concentrations of melatonin, and of its major
      metabolite 6-sulfatoxymelatonin (aMT6s), before and after hemodialysis. Serum
      samples taken during morning hours from a control group (n=11) with intact
      kidneys served as controls. Patients were dialyzed for approximately 4 hr between
      07:00 and 13:00 hr (S1), between 13:00 and 20:00 hr (S2), or between 18:30 and
      22:30 hr (S3). Mean melatonin concentrations before hemodialysis were highly
      elevated when compared with the controls (40.6 vs. 6.7 pg/mL; P<0.001). Although
      melatonin levels were decreased to 20.3 pg/mL after dialysis, they were still
      well above the control levels. Likewise, aMT6s concentrations before dialysis
      were highly elevated in ESRD patients before dialysis when compared with controls
      (39.5 vs. 2.0 pg/mL; P<0.001), and also decreased by dialysis to levels still
      well above control levels (25.3 pg/mL). Clearance efficacy was better for
      melatonin (48.9%) than for aMT6s (36.6%; P<0.05). In ESRD patients, a diurnal
      rhythm for melatonin was observed (S1, 45.1 pg/mL; S2, 31.5 pg/mL; S3, 48.7
      pg/mL; P<0.05), indicating that the normal synthesis rhythm is maintained. None
      of the following secondary disorders were correlated with melatonin
      concentrations: insomnia, delayed sleep onset, night-time arousals, and restless
      leg syndrome. The reason for this observation is probably the melatonin
      concentrations, which were so high that no sub-classification could be
      identified. It is concluded that in ESRD patients, hemodialysis is unable to
      decrease elevated levels of melatonin and aMT6s to normal values. It is
      speculated that some of the secondary disorders in ESRD are caused by
      supraphysiological concentrations of melatonin.

PMID- 11589757
TI  - Effect of melatonin on cell growth, metabolic activity, and cell cycle
      distribution.
AB  - We have recently demonstrated that the pineal secretory product melatonin
      inhibits the key transcriptional regulator nuclear factor-kappa B (NF-kappa B).
      As the activation of NF-kappa B is known to regulate the expression of cellular
      genes associated with cell cycle progression, cell growth, and differentiation,
      we investigated the effect of melatonin treatment on several cellular processes.
      These include cell viability, metabolic activity, and cell cycle phase
      distribution. Human embryonic kidney (293S) cells were treated with melatonin at
      concentrations of 0.02, 0.2, or 2 mM. When cell viability was measured 24, 48,
      and 72 hr after continuous exposure to melatonin using the trypan blue dye
      exclusion method, no significant cell death was observed. Even after exposure to
      2 mM melatonin for 72 hr, cell viability remained at 98%. In contrast, another
      antioxidant compound, pyrrolidine dithiocarbomate (PDTC), at a 2 mM concentration
      reduced cell viability to 80.7+/-2.1% as early as 24 hr compared with untreated
      controls (P<0.05). When the metabolic activity was determined at 24, 48, and 72
      hr using the colorimetric MTT assay, no significant changes in metabolic activity
      were observed. Even if the cells were treated with 10 mM melatonin for 72 hr, the
      metabolic activity was similar to that of the control cells. When cell cycle
      analysis was performed by flow cytometry, no marked difference in cell cycle
      distribution was observed. Melatonin at a concentration of 2 mM, however, did
      slightly alter the cell cycle (percentage of S phase cells) at 48 hr. This study
      revealed that when 293S cells are treated with concentrations of melatonin up to
      2 mM, no significant alterations in three important cellular functions occurred.
      Exogenously added melatonin appeared to have a limited influence on the normal
      functioning of the cells even when the exposure continued for 72 hr.

PMID- 11589758
TI  - Daytime 50 Hz magnetic field exposure and plasma melatonin and urinary 6
      sulfatoxymelatonin concentration profiles in humans.
AB  - Concern about the health effects of extremely low frequency (ELF) magnetic fields
      (MF) has been raised by epidemiological studies indicating an association between
      certain cancers and living near power lines or working in high electric field
      environments. Alterations in pineal function have been proposed as a mechanism
      through which power-frequency MFs may interact with living organisms. A double
      blind laboratory study was performed to evaluate daytime exposure effects of 100
      microT root mean square (rms) 50 Hz MF. Three head exposure sessions of 30 min
      each were performed: sham, continuous, and intermittent (15 s on/off cycles) MFs
      were presented to each subject in early or late afternoon (13:30 or 16:30 hr).
      Twenty-one healthy male volunteers (20-27 yr old) participated in these 3-weekly
      experimental conditions. Blood samples were drawn for serum melatonin
      measurement, hourly at night (from 20:00 to 07:00 hr) under controlled
      environmental conditions. Urinary excretion of 6-sulfatoxymelatonin (aMT6s), the
      main melatonin metabolite, was measured for a 17 hr period, by means of urine
      samples taken at 19:00 hr (14:00-19:00 hr "afternoon period"), 23:00 hr (19:00
      23:00 hr "evening period"), and 07:00 hr, day 2 (23:00-07:00 hr day 2 "night-time
      period"). There were no significant differences in either plasma melatonin or in
      aMT6s excretion profiles in the three experimental conditions. However, a
      tendency for a smaller increase of night-time urinary aMT6s after continuous MF
      exposure was found (P=0.08) particularly in men with the lower excretion rate of
      aMT6s ("Low Group") (P=0.07). We conclude that this study does not indicate that
      daytime acute MF exposure influences either melatonin secretion or aMT6s
      excretion. Inter-individual differences in pineal production of melatonin,
      however, have to be taken into account in further studies.

PMID- 11589759
TI  - Melatonin suppresses homocysteine enhancement of serotonin-induced
      vasoconstriction in the human umbilical artery.
AB  - Hyperhomocysteinemia is a major and independent risk factor for vascular disease.
      Oxidative stress is a possible mechanism for homocysteine (Hcy)-induced
      endothelial dysfunction. Herein, we evaluated the antioxidant property of
      melatonin as related to the vasospastic effect of Hcy on the human umbilical
      artery. Helical strips of human umbilical arteries with intact endothelium were
      obtained at elective Caesarean delivery between 37 and 39 wks of gestation.
      Changes in 5-hydroxytryptamine (5-HT)-induced vasoconstriction were measured.
      Arterial strips were treated with FeSO4 (10 microM) and Hcy (10 or 100 microM) or
      pre-treated with a hydroxyl radical (.OH) scavenger (mannitol, 20 mM), a
      cyclooxygenase inhibitor (indomethacin, 20 microM), nitric oxide (NO) synthesis
      inhibitor (L-NG-monomethylarginine, LNMA, 200 microM), or melatonin (1 or 10
      microM). Hcy potentiated 5-HT-induced constriction in a concentration-dependent
      manner. Pre-treatment with mannitol significantly suppressed the vasospastic
      effect of Hcy. LNMA augmented the vasospastic effect of Hcy, but indomethacin did
      not. Melatonin significantly suppressed the vasospastic effect of Hcy in a
      concentration-dependent manner. These findings suggest that Hcy potentiates 5-HT
      induced vasoconstriction in the human umbilical artery, possibly by suppressing
      bioavailable NO. Melatonin protects against the vasospastic effect of Hcy, most
      likely by scavenging.OH arising from Hcy autooxidation.

PMID- 11589760
TI  - Comparison of immune parameters of sheep with naturally high or low plasma
      concentrations of melatonin.
AB  - Studies in rodents and humans have suggested that the pineal gland and its
      secretory product melatonin play an important role in the modulation of the
      immune system. In this study, we tested the hypothesis of a difference in immune
      parameters between ewes with naturally high vs. low circulating melatonin. Thus,
      two comparable groups of 10 Ile-de-France sheep were selected from a large flock,
      for their naturally high and low plasma concentrations of melatonin. The mean
      plasma melatonin concentrations during daytime (09:00 hr) and nighttime (24:00
      hr) were, respectively, 9 and 664 pg/mL (high group) and 5 and 169 pg/mL (low
      group; P<0.01). Animals from both groups were subjected to various in vitro and
      in vivo measurements of the characteristics of their immune system. The total
      number of white blood cells (lymphocytes, polymorphonuclears, and monocytes) and
      the assessment of the sub-populations of blood lymphocytes (T4, T8, T19, B, and
      monocytes) did not show any significant differences between the two groups,
      sampled during day or night. The level of blood leukocytes proliferation after in
      vitro culture with ConA, LPS, or CWF stimulation, before or after experimental
      immunization, did not reveal any differences. No significant differences were
      registered in the production of antibodies between the two groups of animals. The
      results of the present experiment suggest that in natural conditions a high level
      of circulating melatonin does not modify the activity of the immune system in
      sheep.

PMID- 11589761
TI  - Altered melatonin production in TGR(mREN2)27 rats: on the regulation by
      adrenergic agonists, antagonists and angiotensin II in cultured pinealocytes.
AB  - Transgenic TGR(mREN2)27 rats (TGR), carrying an additional mouse renin gene, are
      characterized by severe hypertension, an inverse circadian blood pressure
      profile, a blunted response to photic entrainment signals, and an increased
      nocturnal production of the pineal hormone melatonin. In order to evaluate the
      contribution of the over-expressed renin-angiotensin system to the function of
      the pineal gland in TGR, we studied the adrenergic and angiotensin II (Ang II)
      mediated regulation of melatonin synthesis using dispersed pinealocytes from TGR
      and from Sprague-Dawley control rats (SDR). Isoproterenol was more effective in
      stimulating melatonin release in pinealocytes from TGR than from SDR, whereas the
      maximum effect of norepinephrine (NE) stimulation did not differ between the
      strains. Prazosin reduced the NE-mediated melatonin release only in SDR but not
      in TGR pinealocytes. Competition experiments with (+/-)-, (+)-, (-)-propranolol
      and (+/-)-atenolol revealed one homogeneous population of beta1-adrenoceptors.
      Ang II had no significant effect on basal or isoproterenol-induced melatonin
      release in either strain. In conclusion, TGR pinealocytes were more sensitive to
      beta-adrenergic stimulation than SDR pinealocytes, but lacked the alpha1
      adrenergic potentiation of beta-adrenergic induced melatonin release. The renin
      angiotensin system was not directly involved in the regulation of melatonin
      synthesis by rat pinealocytes in vitro.

PMID- 11589762
TI  - Circadian abnormalities in older adults.
AB  - This study examined the circadian phase adjustment of symptomatic elders ages 60
      79 years in comparison with that of young, healthy adults ages 20-40 years.
      Seventy-two elders with complaints of insomnia or depression, and 30 young,
      healthy adults were assessed for 5-7 days at home. Sleep and illumination were
      recorded with Actillume wrist monitors and sleep diaries. Urine was collected
      over two 24-hr periods and assayed for 6-sulphatoxymelatonin (6-smt). The
      volunteers were then observed continuously for 5 nights and 4 days in the
      laboratory. In the laboratory, sleep periods were fixed at 8 hr with
      polysomnographic assessment of sleep, apnea-hypopnea, and nocturnal myoclonus.
      Circadian dispersion, defined as the mean variation of 6-smt acrophase from the
      median age-specific acrophase, was significantly greater in the older vs. young
      adults. Likewise, circadian malsynchronization, defined as the absolute number of
      hours (advance or delay) between the 6-smt acrophase and the middle of the sleep
      period, was significantly greater in the older vs. young volunteers. For the
      older volunteers, multiple regressions were calculated associating sleep with
      potential correlates of sleep disturbance. Nocturnal myoclonus and circadian
      malsynchronization were more strongly associated with sleep impairment than other
      factors (e.g., sleep apnea, depression). These observations suggest that
      circadian malsynchronization might be a common and significant cause of disturbed
      sleep among adults over age 60.

PMID- 11589763
TI  - Presence of oxytocinergic neuronal-like cells in the bovine pineal gland: an
      immunocytochemical and in situ hybridization study.
AB  - In the last decade, there is more and more evidence showing the role of the
      central innervation of the pineal gland, but there are controversies around the
      intra or extrapineal origin of oxytocin found within the pineal tissue. In order
      to check the amount and the site of synthesis of oxytocin in the bovine pineal
      gland, we performed a morphological and chromatographic study. The anatomical
      distribution of the pineal oxytocin was explored by immunohistochemistry and in
      situ hybridization for the corresponding mRNA. The results confirm the presence
      of oxytocinergic fibres in the bovine pineal, some of them endowed with big
      varicosities. Immunohistochemistry also displayed neuronal-like cells in the
      pineal body. The in situ hybridization for the mRNA encoding pre-pro/oxytocin-NFZ
      I used a mixture of three oligonucleotide probes labelled with (35)S. This
      allowed identification of positive cells in the bovine pineal. The content in
      oxytocin was evaluated by radioimmunoassay during 5 months, from July to
      November, and the peptidic extract revealed an increase of pineal oxytocin
      immunoreactivity in September as compared with July or November. The significance
      of intrinsic oxytocin innervation of the bovine pineal gland, as well as the
      threefold increase of the oxytocin content in the pineal in September, remains to
      be elucidated.

PMID- 11589764
TI  - Melatonin protects against oxidized low-density lipoprotein-induced inhibition of
      nitric oxide production in human umbilical artery.
AB  - We evaluated the antioxidative effect of melatonin on the oxidized low-density
      lipoprotein (LDL)-induced impairment of nitric oxide (NO) production in human
      umbilical artery, which may be the prime cause of endothelial dysfunction in pre
      eclampsia. Umbilical artery sections with intact endothelium were obtained from
      healthy pregnant women who were delivered between 37 and 40 wk of gestation. The
      production of NO in the umbilical arteries was stimulated by adding L-arginine
      followed by incubation for 60 min. NO concentrations were estimated by measuring
      nitrite ions (NO(2) using high-performance liquid chromatography. LDL was
      oxidized by incubation with 5 microM CuSO(4) at 37 degrees C for 4 hr, followed
      by dialysis at 4 degrees C for 24 hr. Prior to the addition of L-arginine, the
      segments were treated with native or oxidized LDL (0, 50, 100, 200, 400
      microg/mL), or were pre-treated with either mannitol (50 mM) or melatonin (20,
      100, 500 microM) before adding oxidized LDL. Changes in L-arginine-induced NO(2)(
      ) production were expressed as a percentage of NO(2)(-) production at the end of
      pre-incubation. Treatment with oxidized LDL significantly reduced L-arginine
      induced NO(2)(-) production (P<0.05), while NO(2)(-) production did not change by
      incubation with native LDL. Pre-treatment with melatonin significantly increased
      NO(2)(-) production that had been decreased by oxidized LDL (P<0.05). Similarly,
      pre-treatment with mannitol reversed the oxidized LDL-induced reduction in NO(2)(
      ) production (P<0.05). These results indicate that melatonin protects against
      oxidized LDL-induced inhibition of NO production in the endothelium of human
      umbilical arteries, most likely through its ability to scavenge hydroxyl
      radicals.

PMID- 11589765
TI  - Serum thioredoxin elucidates the significance of serum ferritin as a marker of
      oxidative stress in chronic liver diseases.
AB  - BACKGROUND/AIMS: Serum thioredoxin (TRX) levels have recently been established as
      an indicator of oxidative stress in various diseases. The aim of the present
      study was to clarify the clinical significance of serum ferritin in chronic liver
      diseases. METHODS: Levels of ferritin, transferrin saturation (TS), aspartate
      aminotransferase (AST), and TRX were measured in the sera of patients with
      chronic hepatitis C (CH-C, n=92), chronic hepatitis B (CH-B, n=28), nonalcoholic
      fatty liver (FL, n=31), or alcoholic liver diseases (ALD, n=17). Serum TRX levels
      were evaluated with a recently established sandwich enzyme-linked immunosorbent
      assay kit. RESULTS: Serum TRX levels were significantly higher in CH-C, FL, and
      ALD than in healthy volunteers. A larger proportion of patients with CH-C, FL,
      and ALD had elevated levels of serum ferritin than CH-B. Serum ferritin levels
      were positively correlated with levels of TS, AST, and TRX in CH-C, but were
      merely correlated with TS values in CH-B. Ferritin levels were also well
      correlated with AST and TRX, but not with TS in FL and ALD. CONCLUSION: Oxidative
      stress, which was evaluated by measuring serum TRX, in addition to storage iron
      and hepatocyte damage is a cause of increasing serum ferritin levels in chronic
      liver diseases. An elevated serum ferritin level, which was correlated with TS,
      indicates that iron-induced oxidative stress contributes to CH-C. Elevated
      ferritin levels in FL and ALD may be mostly due to iron-unrelated stresses.

PMID- 11589766
TI  - Immunohistochemical and electron microscopic study of extrinsic hepatic
      reinnervation following orthotopic liver transplantation in rats.
AB  - BACKGROUND/AIMS: Because little has been known about the morphological and
      functional consequences of liver transplantation on hepatic autonomic nerves, we
      examined the time-course of extrinsic hepatic innervation at the level of the
      porta hepatis of liver allografts. METHODS: Orthotopic liver transplantation was
      performed using male Lewis rats. Crosscut tissue specimens were obtained
      postoperatively for up to 6 months from the porta hepatis of transplanted livers,
      and processed for immunohistochemical staining for protein gene product 9.5 (PGP
      9.5) and growth-associated protein 43 (GAP-43), and for transmission electron
      microscopy (TEM). RESULTS: Extrinsic nerve fibers at the porta hepatis stained
      positively for PGP 9.5 throughout the entire study period. In contrast, the
      immunoreactivity of GAP-43 was negative at postoperative day (POD) 1 and 2. GAP
      43-positive nerves were first observed to appear in the porta hepatis at POD 3.
      The immunoreactivity of GAP-43 remained positive thereafter until 3 months post
      OLT, and became negative in all the specimens at 4 months post-OLT. Transmission
      electron microscopy demonstrated a small number of regenerating axons existing
      among many degenerating axons at POD 3. At 3 months post-OLT, most regenerating
      axons had been fully ensheathed by the cytoplasm of Schwann cells, although their
      density remained at a lower level compared with normal. CONCLUSION: The results
      of this study suggest that liver allografts become extrinsically reinnervated,
      with the regenerating axons reaching the hepatic hilus 3 days after
      transplantation. The process of extrinsic hepatic reinnervation is considered to
      almost terminate 4 months after transplantation in rats.

PMID- 11589767
TI  - Caspase activation during hepatocyte apoptosis induced by tumor necrosis factor
      alpha in galactosamine-sensitized mice.
AB  - BACKGROUND/AIMS: To clarify the mechanism of hepatocyte apoptosis induced by
      tumor necrosis factor-alpha (TNF-alpha), caspase cascade and ceramide formation
      were investigated in the liver of D-galactosamine (GalN)-sensitized mice treated
      with TNF-alpha. METHODS: Seven-week-old male BALB/c mice were intraperitoneally
      injected with 20 mg GalN 30 min prior to the intravenous injection of recombinant
      mouse TNF-alpha (0.5 microg/mouse). Cytochrome c release and processing of
      procaspases in the liver were analyzed by Western blotting. Activities of
      caspases were measured using chromogenic peptides as substrates. Ceramide content
      was determined using Escherichia coli diacylglycerol kinase. RESULTS: Apoptosis
      of hepatocytes was observed in mice treated with both GalN and TNF-alpha
      (GalN/TNF-alpha), but not GalN or TNF-alpha alone. Activation of caspases-9 and 
      3, and cytochrome c release were observed only in liver from mice treated with
      GalN/TNF-alpha. In a cell-free system, processing of procaspases-9 and -3, and
      cytochrome c release were observed in the postnuclear fraction of liver obtained
      from GalN/TNF-alpha-treated mice, but not in that from control mice. Processing
      of procaspase-3 was inhibited by a caspase-9 inhibitor, but not by inhibitor for
      caspase-8 or -2. In a reconstitution assay system, procaspase-9 processing
      occurred, when both cytosol and membrane fractions were obtained from the liver
      of mice treated with GalN/TNF-alpha. Ceramide accumulation was observed only in
      apoptotic liver and preceded cytochrome c release and caspase activation.
      CONCLUSION: Cytochrome c release and caspase-9 activation are required for the
      activation of executor caspase-3 in TNF-alpha-induced hepatocyte apoptosis, but
      caspases-8 and -2 play, if any, a minimal role. Ceramide may be implicated in
      this apoptotic process.

PMID- 11589768
TI  - Characteristics of the hepatic stellate cell-selective carrier mannose 6
      phosphate modified albumin (M6P(28)-HSA).
AB  - BACKGROUND/AIMS: Drug targeting to hepatic stellate cells (HSC) may improve the
      pharmacological effects of antifibrotic drugs. Recently, albumin substituted with
      28 mannose 6-phosphate moieties (M6P(28)-HSA) was found to distribute selectively
      to HSC in fibrotic rat livers. To assess whether this albumin can be used as a
      carrier for intracellular drug delivery, we explored the cellular handling of
      M6P(28)-HSA in HSC. METHODS/RESULTS: Application of competitive substrates for
      the M6P/IGFII receptor or other receptors showed that the binding of M6P-HSA to
      the M6P/IGFII receptor is specific. Binding was strong to activated HSC, but not
      to quiescent HSC. Furthermore, M6P(28)-HSA was extensively internalized by these
      cells. Using monensin, a specific inhibitor of the lysosomal pathway, proof was
      obtained that M6P-HSA is endocytosed via this route. The experiments performed
      with tissue slices, prepared from rat and human livers, revealed a specific
      binding and uptake of M6P(28)-HSA in both normal and cirrhotic livers. In livers
      from cirrhotic patients, HSC contributed predominantly to the uptake of this
      neoglycoprotein. CONCLUSIONS: Based on our in vivo data demonstrating the HSC
      selectivity and on our in vitro data demonstrating binding and rapid
      internalization in activated HSC, we conclude that M6P(28)-HSA is applicable as a
      stellate cell-selective carrier for antifibrotic drugs that act intracellularly.
      This may have implications for the design of new strategies for the treatment of
      liver fibrosis.

PMID- 11589769
TI  - Histological patterns of rejection using oral microemulsified cyclosporine and
      tacrolimus (FK506) as monotherapy induction after orthotopic liver
      transplantation.
AB  - BACKGROUND/AIMS: We describe the histological patterns of rejection in liver
      transplant recipients using induction therapies with cyclosporine and tacrolimus
      monotherapy compared with standard triple therapy as historical control. METHODS:
      Patients formed part of the initial cohort in an open-labelled, randomised pilot
      study and were selected consecutively if they had histological rejection and no
      other confounding diagnoses. There were 13 patients in the cyclosporine
      monotherapy group (CsA), 11 in the tacrolimus monotherapy group and 13 in the
      triple therapy group (CAP). The histology of liver biopsies was reassessed
      blindly and the severity of rejection was recorded. RESULTS: The total Royal Free
      Hospital (RFH) rejection scores as well as other histological features (zone 3
      haemorrhage, apoptosis in zones 1 and 3, steatosis, cholestasis, nuclear
      vacuolation, lymphoblasts and ballooning) were comparable in the three groups.
      There was no difference in individual components of the histological features
      comprising the diagnosis of rejection, except that the portal inflammation score
      was significantly lower in the tacrolimus group when compared with the CsA group
      (p=0.04). There was no significant difference in the number of patients with
      moderate/severe rejection between the three groups. Overall, there was no
      significant increase in histological severity of rejection in the monotherapy
      groups. CONCLUSIONS: The results suggest that the monotherapy may be as effective
      as the triple therapy in the initial post-transplant phase and that no particular
      graft histological changes were associated with the type of treatment.

PMID- 11589770
TI  - HCV and cancer: a case-control study in a high-endemic area.
AB  - BACKGROUND/AIMS: HCV is a RNA virus that cannot be integrated with the host
      genome; it can, however, exert its oncogenic potential indirectly by contributing
      to the modulatory effects of the host immune system, probably through a capacity
      to elude the immune system. We have carried out a case-controlled study on the
      different oncological pathologies which have, to date, been shown to have a
      relationship with HCV. METHODS: We screened 495 patients with different types of
      cancer: 114 cases of liver cancer, 41 of multiple myeloma, 111 non-Hodgkin's
      lymphomas, 130 thyroid cancers, 63 cases of Hodgkin's disease. The controls were
      226 patients with no history of cancer. The relationship between each cancer and
      HCV infection was assessed by means of odds ratios (OR) and corresponding 95%
      confidence intervals. RESULTS: Risks were greater for liver cancer (OR=32.9 95%
      CI 16.5-65.4, p<0.0001), multiple myeloma (OR=4.5 95% CI 1.9-10.7, p=0.0004) and
      B-cell non-Hodgkin's lymphoma (OR=3.7 95% CI 1.9-7.4, p=0.0001). For Hodgkin's
      disease there was no significant association (p=0.3). An association between HCV
      and thyroid cancer was noted (OR=2.8 95% CI 1.2-6.3, p=0.01). CONCLUSION: Our
      study is particularly important for public health since the high prevalence of
      HCV in the South of Italy gives reason to expect increases in not only liver
      cancer, but also tumors associated with the immune system and thyroid cancer in
      years to come.

PMID- 11589771
TI  - Estrogen receptor levels and lipid peroxidation in hepatocellular carcinoma with
      hepatitis C virus infection.
AB  - AIMS/BACKGROUND: Our preliminary studies showed that estradiol suppresses hepatic
      carcinogenesis and fibrogenesis in animal models. Hepatic estrogen receptors
      (ERs) medicate estradiol action in the liver. This study was performed to assess
      possible implications of menopause and hepatic ER levels for the development of
      cirrhosis with hepatocellular carcinoma (HCC). METHODS: One thousand, one hundred
      and ninety-nine consecutive HCC patients with hepatitis C virus (HCV)-related
      cirrhosis were divided into two groups, based on a menopausal age of 49 years.
      Liver tissues were obtained during surgical resection of HCC and metastatic liver
      tumor. RESULTS: The proportion of females among the HCC subjects < or =49 years
      of age was significantly lower (15.0%) than was the proportion of females among
      subjects >49 years of age (29.8%). Univariate analysis showed that HCV-related
      cirrhotic patients who developed HCC were more likely to have low hepatic levels
      of ER and copper-zinc superoxide dismutase (CuZn-SOD) protein and a high hepatic
      level of a lipid peroxidation product, malondialdehyde (MDA). Logistic regression
      identified age greater than 49 years (odds ratio [OR]: 7.9, 95% confidence
      interval [CI]: 2.8-21.3), male sex (OR: 3.5, 95% CI: 1.3-10.2), a decreased ER
      level (OR: 16.8, 95% CI: 7.3-34.6), and an increased MDA (OR: 8.3, 95% CI: 2.8
      24.0) as the variables independently associated with the development of HCC in
      HCV-infected patients with cirrhosis. ER level was significantly correlated with
      CuZn-SOD level (r=0.583) and was inversely proportional to MDA level (r=-0.553).
      The study also showed that ER levels in the cirrhotic livers from premenopausal
      females were significantly higher than in male cirrhotic livers. CONCLUSIONS:
      These findings suggest that increased lipid peroxidation and impaired SOD
      function in the liver may be associated with decreased hepatic ER levels in HCV
      infected patients with cirrhosis and HCC, and that HCV-related cirrhotic women
      before menopause might have the ability to protect against developing HCC via
      hepatic ER.

PMID- 11589772
TI  - The insulin-like growth factor binding protein 3 ternary complex is reduced in
      cirrhosis.
AB  - BACKGROUND/AIMS: In healthy adults, serum insulin-like growth factor I (IGF-I),
      IGF binding protein 3 (IGFBP-3) and acid labile subunit (ALS) form a 150-kDa
      ternary complex under the control of growth hormone (GH). Approximately 80-90% of
      circulating IGF-I is bound to the ternary complex. In cirrhosis the GH/IGF axis
      is severely disturbed and the individual components of the ternary complex are
      reduced. However, the degree of ternary complex formation in cirrhosis has not
      previously been described. METHODS: Serum IGF-I, IGFBP-3, ALS, the 150-kDa
      ternary complex and IGFBP-3 proteolysis were all measured in six compensated and
      six decompensated cirrhotic patients and compared to six healthy controls.
      RESULTS: Patients with compensated cirrhosis had decreased levels of IGF-I (55%),
      IGFBP-3 (64%) and ALS (53%), and in the decompensated patients these levels were
      decreased even further: IGF-I (32%), IGFBP-3 (37%) and ALS (27%) compared to
      healthy controls. The levels of the ternary complex followed this pattern, with
      low levels seen in the compensated patients (66%) and a further reduction in the
      decompensated patients (27%). Ternary complex levels correlated negatively with
      the Child-Pugh score. No increase in IGFBP-3 proteolysis was found in cirrhotic
      patients compared to healthy controls. CONCLUSION: Cirrhosis is associated with
      reduced levels of the 150-kDa ternary IGFBP-3 complex correlating with the degree
      of liver disease.

PMID- 11589773
TI  - Inclusion body myositis associated with hepatitis C virus infection.
AB  - The case of a 77-year-old woman with hepatitis C virus infection with a 5-year
      history of muscle weakness and mild disturbance of gait is reported. Steroid
      therapy did not improve her symptoms. She developed HCV-related liver cirrhosis
      and hepatocellular carcinoma, and muscle biopsy revealed inclusion body myositis.
      Immunohistochemistry showed that the nonstructural region of HCV and 8-hydroxy-2'
      deoxyguanosine, a marker of DNA damage by reactive oxygen species, were present
      in striated muscle cells of this patient.

PMID- 11589774
TI  - Fatal liver infarction after transjugular intrahepatic portosystemic shunt
      procedure.
AB  - Hepatic infarction is a rare disease. We describe here a cirrhotic patient with
      end-stage renal failure and recurrent tense ascites with fatal hepatic infarction
      after transjugular intrahepatic portosystemic shunt (TIPS) procedure. Abdominal
      ultrasound, radionuclide liver scan, abdominal computed tomography scan, and
      finally liver biopsy established the diagnosis. The mechanism causing the infarct
      is not clear. However, as the infarct appeared after the patient had an episode
      of shock and disseminated intravascular coagulation, it could well be that the
      concomitant hepatic arterial insufficiency contributed to the infarct. Physicians
      should be aware of this possible catastrophic complication.

PMID- 11589775
TI  - The age-related immunity in cattle to Babesia bovis infection involves the rapid
      induction of interleukin-12, interferon-gamma and inducible nitric oxide synthase
      mRNA expression in the spleen.
AB  - Young calves possess a strong innate immunity against Babesia bovis infection
      that lasts for approximately 6 months after birth and is abrogated with the
      removal of the spleen. This immunity is characterized as cellular involving a
      soluble mediator. Nitric oxide has been implicated by virtue of its babesiacidal
      affects in vitro, but questioned to be as effective in vivo, due to its ability
      to downregulate type-1 immunity. Spleen cells were obtained from 4-month-old
      calves and adult steers and processed for monitoring cytokine and inducible
      nitric oxide synthase (iNOS) mRNA expression during the response to initial B.
      bovis infection. The data provided evidence of a transient role for nitric oxide
      in innate immunity, characterized by brief iNOS induction in the spleen of calves
      that was not detectable in the spleens of adults. The iNOS message followed the
      early induction of interleukin (IL)-12 and interferon (IFN)-gamma message in
      calves. The induction of IL-12 and IFN-gamma message in adults was delayed until
      IL-10 message was induced. Transformation growth factor-beta mRNA expression
      levels were greater in spleen cells from adults early in infection and then
      declined, whereas expression levels increased in spleen cells from calves later
      in the infection process. Together, the data support the concept of 'first come,
      first serve' cytokine influence over cellular activities, the importance of a
      type-1 response in the control of an initial infection and the need for tight
      regulation in order to prevent pathology associated with over production of
      nitric oxide and inflammatory cytokines.

PMID- 11589776
TI  - Antibody-dependent cell-mediated cytotoxicity to newly excysted juvenile Fasciola
      hepatica in vitro is mediated by reactive nitrogen intermediates.
AB  - Passive intraperitoneal transfer of sera from Fasciola hepatica-infected sheep,
      cattle or rats can protect naive rats from F. hepatica infection, suggesting a
      parasite killing mechanism within the peritoneal cavity that is dependent on the
      presence of parasite-specific antibody. We investigated antibody-dependent cell
      mediated cytotoxicity by resident peritoneal lavage cell populations, containing
      large numbers of monocytes/macrophages, as a potential host resistance mechanism
      by which juvenile flukes could be killed within the peritoneal cavity of naive
      rats. Comparative studies were conducted using cell populations containing large
      numbers of monocytes/macrophages from sheep. The results demonstrate that
      monocyte/macrophage-rich lavage cell populations from rat and sheep differ
      substantially in their ability to generate nitric oxide. Only resident rat
      peritoneal lavage cells were able to mediate antibody-dependent cell-mediated
      cytotoxicity against newly excysted juvenile liver fluke. The mechanism of
      cytotoxicity was dependent on, and directly proportional to, the production of
      nitric oxide and required attachment of effector cells to the newly excysted
      juvenile liver fluke tegument, which occurred following the addition of sera from
      F. hepatica-infected animals. This is the first report demonstrating a mechanism
      of cell-mediated cytotoxicity to newly excysted juvenile liver fluke.

PMID- 11589778
TI  - Nitric oxide and reactive nitrogen intermediates during lethal and nonlethal
      strains of murine malaria.
AB  - The virulence of Plasmodia depends partly on the strain of parasite and partly on
      the host. In this study, Plasmodium berghei N/13/1A/4/203 caused the death of
      mice, whereas Plasmodium chabaudi chabaudi AS was not lethal. Current opinion is
      that nitric oxide (NO) and other reactive nitrogen intermediates (RNI) are
      produced in several host organs during malaria to resist infection or produce
      tissue damage. NO and RNI production in blood or plasma, brain, liver and spleen
      in MF1 mice was investigated during P. berghei and P. c. chabaudi infection, in
      order to help determine whether changes in NO production are beneficial or
      detrimental to the host in vivo. NO production was measured both directly and
      indirectly as nitrites and nitrates, to represent RNI. No changes in blood NO
      were detected in P. berghei infected mice, but increases were observed in brain,
      liver and spleen. In P. c. chabaudi infected mice, rises in NO concentration were
      observed in blood and spleen, whereas a decline in liver NO was seen, but there
      were no changes in brain. Liver contained the highest concentration of RNI, but
      increasing concentrations were seen in both plasma and spleen in both P. berghei
      and P. c. chabaudi infected mice. These results show that NO and RNI production
      alters during murine malaria. The changes depend upon the tissue, the day of
      infection, the degree of parasitaemia, the strain of Plasmodia and the method of
      measuring NO biosynthesis. Lethal P. berghei induced NO production in the mid and
      late stages of infection in mice when parasitaemia was high, whereas in nonlethal
      P. c. chabaudi infection, NO production was increased in the early and late
      stages when parasitaemia was low. These data are consistent with a role for NO in
      the protection of the MF1 mouse against Plasmodia. Failure to clear the parasite
      is associated with evidence of increased NO production in brain and liver, which
      may contribute to the pathology of malaria, but this hypothesis requires
      confirmation from other experimental approaches.

PMID- 11589777
TI  - Anti-interleukin-8 activity of tick salivary gland extracts.
AB  - Interleukin-8 (IL-8) is one of many mammalian chemokines (chemotactic cytokines)
      that direct mammalian inflammatory and immune cells to sites of injury and
      infection. Chemokines are produced locally and act on leucocytes through
      selective receptors. The principal role of IL-8 is to control the movement and
      activity of neutrophils. To date, several tick species have been shown to
      modulate the production or activity of certain cytokines but none of these are
      chemokines. Using an IL-8 specific ELISA, we showed that salivary gland extracts
      (SGE) from several ixodid tick species (Dermacentor reticulatus, Amblyomma
      variegatum, Rhipicephalus appendiculatus, Haemaphysalis inermis and Ixodes
      ricinus) reduced the level of detectable IL-8. Analyses of fractionated SGE
      revealed one similar peak of activity for D. reticulatus, A. variegatum and R.
      appendiculatus; a second peak, observed for D. reticulatus and A. variegatum,
      differed between the two species. Using radiolabelled IL-8, SGE and peak activity
      fractions of D. reticulatus were shown to bind the chemokine, and to inhibit
      binding of IL-8 to its receptors on human granuolocytes enriched for neutrophils.
      The biological significance of these observations was demonstrated by the ability
      of SGE to inhibit IL-8 induced chemotaxis of human blood granulocytes. Future
      isolation and characterization of the active molecules will enable determination
      of their functional roles in bloodfeeding and effect on tick-borne pathogen
      transmission.

PMID- 11589779
TI  - HTLV-1 decreases Th2 type of immune response in patients with strongyloidiasis.
AB  - Eosinophils, immunoglobulin (Ig)E and cytokines have important roles in defence
      mechanisms against helminths. In this study, the influence of HTLV-1 infection,
      characterized by a Th1 type of immune response, was evaluated on the cytokine
      pattern and parasitic specific IgE response in patients with strongyloidiasis.
      Patients were divided into four groups: strongyloidiasis without HTLV-1
      infection, strongyloidiasis with HTLV-1, HTLV-1 without strongyloidiasis and
      controls without either helminth infection or HTLV-1. The cytokine profile was
      determined in supernatants of mononuclear cells stimulated with Strongyloides
      stercoralis crude antigen and the parasite specific IgE was measured by ELISA.
      Patients coinfected with HTLV-1 had higher levels of interferon (IFN)-gamma and
      interleukin (IL)-10 (P < 0.05) and lower levels of IL-5 and IgE (P < 0.05) than
      patients with strongyloidiasis without HTLV-1. There was an inverse relationship
      between IFN-gamma and IL-5 (P = 0.01; rs = - 0.37) and between IFN-gamma and
      parasite specific IgE (P = 0.01; rs = - 0.39), and a direct relationship between
      IFN-gamma and IL-10 (P = 0.04; rs = 0.35). These data show that coinfection with
      HTLV-1 decreases IL-5 and IgE responses in patients with strongyloidiasis
      consistent with a relative switch from Th2 to Th1 response. Immunological
      responses such as these are important in the control of this helminthic
      infection.

PMID- 11589780
TI  - Antibody responses in onchocerciasis as a function of age and infection
      intensity.
AB  - Onchocerciasis is caused by the filarial nematode Onchocerca volvulus and is a
      major public health problem in West and Central Africa. With only partial and
      long-term treatment currently available, there is a need to develop a suitable
      vaccine. We analysed the antibody response to infective L3 larvae because this
      stage is thought to be associated with host protective immunity. In addition, we
      have related our findings to the age, gender and current infection intensity of
      our participants: variables that may significantly influence antibody production.
      Interestingly, whilst 90% of our study group were seropositive for adult specific
      immunoglobulin (Ig)E, only 23% produced L3 specific IgE. This is in contrast to
      IgG4 where seropositivity was comparable at 96% and 92%, respectively.
      Furthermore, IgG levels were significantly affected by age and the intensity of
      infection but unaffected by host gender. This finding is independent for the IgG
      subclass (IgG1, IgG2, IgG3 and IgG4) and its specificity (L3 versus adult
      antigen). In summary, we show that L3 larvae induce little specific IgE and the
      antibody response shows a different isotype balance than that against adult
      antigens. Both host and parasite variables can influence antibody production in
      this disease.

PMID- 11589781
TI  - Gene induction by Phenobarbital: an update on an old question that receives key
      novel answers.
AB  - Phenobarbital has long been used as a sedative and antiepileptic drug. The drug
      is the representative of a myriad of lipophilic molecules able to evoke a
      pleiotropic response in the liver and also in prokaryotes and flies. A great deal
      of novel information has been obtained in recent years regarding the mechanism of
      cytochrome P450 (CYP) gene induction by phenobarbital. Most importantly, a
      nuclear orphan receptor, the constitutive androstane receptor has been identified
      as a primary determinant of the transcriptional activation of CYP genes in
      response to phenobarbital-like inducers in mammals. Another nuclear receptor, the
      pregnane X receptor can also mediate some of the phenobarbital response, but the
      functional overlap of the two inductive pathways is only partial. The response of
      mammalian CYP2B genes to phenobarbital was abolished in the liver of mice
      carrying a null allele of the constitutive androstane receptor gene, whereas that
      of CYP3A genes was lost in pregnane X receptor knock-out mice.

PMID- 11589782
TI  - Electrophysiological and neurochemical evidence for voltage-dependent Ca(2+)
      channel blockade by a novel neuroprotective agent NS-7.
AB  - The effects of a neuroprotective agent 4-(4-fluorophenyl)-2-methyl-6-(5
      piperidinopentyloxy) pyrimidine hydrochloride (NS-7) on the Ca(2+) currents in
      rat dorsal root ganglion neurones and on the depolarization-evoked nitric oxide
      synthesis, which was estimated from cyclic GMP formation in slices of the rat
      cerebral cortex, were investigated, and its mode of action was compared with
      those of typical Ca(2+) channel blockers. In rat dorsal root ganglion neurones,
      NS-7 (0.3-100 microM) inhibited the whole-cell Ba(2+) currents (IBa) in a voltage
      dependent manner, in which the compound more potently blocked the IBa elicited
      from the holding potential of -40 mV than that induced from -80 mV. In slices of
      rat cerebral cortex, KCl-evoked nitric oxide synthesis was markedly inhibited by
      omega-conotoxin GVIA and omega-agatoxin IVA, but only slightly attenuated by
      nifedipine, suggesting that the response is mediated predominantly through
      activation of N-type and P/Q-type Ca(2+) channels. NS-7 (1-100 microM) inhibited
      the KCl-stimulated nitric oxide synthesis in a manner dependent on the intensity
      of the depolarizing stimuli. Moreover, weak but significant inhibitory effect of
      NS-7 was observed even after wash-out. Similar voltage-dependent inhibition of
      the KCl response was observed by a limited concentration (10 microM) of
      verapamil. These findings indicate that NS-7 in several concentrations blocks
      Ca(2+) channel in a voltage-dependent manner.

PMID- 11589783
TI  - Clonidine attenuates naloxone-induced opioid-withdrawal syndrome in cholestatic
      mice.
AB  - Cholestasis is associated with elevated plasma level of endogenous opioid
      peptides. Naloxone-precipitated withdrawal syndrome has been described in a mouse
      model of acute cholestasis. Thus we aimed at determining whether central
      noradrenergic hyperactivity is involved in manifestation of naloxone-precipitated
      withdrawal syndrome in mice with obstructive cholestasis. Acute cholestasis was
      induced by bile duct resection in mice and physical dependence was observed by
      precipitating a withdrawal syndrome with naloxone (2 mg/kg, intraperitoneally) 5
      days after induction of cholestasis. Administration of clonidine (0.1 mg/kg,
      intraperitoneally), an alpha2-adrenoceptor agonist, 15 min. before naloxone
      injection significantly alleviates withdrawal severity in cholestatic mice.
      However, pretreatment of animals with yohimbine (3 mg/kg, intraperitoneally), an
      alpha2-adrenoceptor antagonist, 15 min. before clonidine blocked this
      ameliorative effect of clonidine. The results of this study support the evidence
      for involvement of the alpha2-adrenoceptors in the withdrawal syndrome of
      cholestasis in a mouse model.

PMID- 11589785
TI  - Increased plasma endothelin-1 and cardiac nitric oxide during doxorubicin-induced
      cardiomyopathy.
AB  - The major limiting factor in long-term administration of doxorubicin is the
      development of cumulative dose-dependent cardiomyopathy and congestive heart
      failure. Although several mechanisms have been suggested to explain the exact
      cause of doxorubicin-induced cardiomyopathy, the role of the vascular endothelium
      derived vasoactive mediators in the pathophysiology of this toxic effect is still
      unknown. Accordingly, the present study has been initiated to investigate whether
      the changes in plasma level of endothelin-1 and nitric oxide along with cardiac
      nitric oxide are associated with the development of doxorubicin-induced
      cardiomyopathy. Doxorubicin was injected with a single dose of 5 mg/kg and every
      other day with a dose of 5 mg/kg, intraperitoneally, to have four cumulative
      doses of, 10, 15, 20 and 25 mg/kg in five separate groups of male rats. An
      additional group receiving a single dose of 20 mg/kg and one receiving normal
      saline were also included in the study. Twenty-four hr after the last dose, the
      animals were sacrificed and the plasma levels of endothelin-1 and nitric oxide in
      addition to cardiac nitric oxide were determined. The results show that
      doxorubicin caused a statistically significant increase of 85%, 76% and 97% in
      plasma endothelin-1 at a cumulative dose levels of 10, 15 and 20 mg/kg,
      respectively. However, the level of plasma nitric oxide remained unchanged.
      Furthermore, doxorubicin treatment resulted in a significant dose-dependent
      increase in serum lactate dehydrogenase and creatine phosphokinase. In contrast,
      the increase in nitric oxide production in cardiac tissue by doxorubicin was not
      dose-dependent with the maximum increase (81%) at a cumulative dose of 10 mg/kg.
      It is worth mentioning that plasma endothelin-1 and cardiac nitric oxide were
      significantly increased at 24 hr after the single dose of 20 mg/kg doxorubicin.
      The increase of plasma endothelin-1 and cardiac nitric oxide with the
      cardiomyopathy enzymatic indices, may point to the conclusion that both
      endothelin-1 and cardiac nitric oxide are increased during the development of
      doxorubicin-induced cardiomyopathy.

PMID- 11589784
TI  - Cholestasis and regulation of genes related to drug metabolism and biliary
      transport in rat liver following treatment with cyclosporine A and sirolimus
      (Rapamycin).
AB  - Cyclosporine A and sirolimus are used alone or in combination as
      immunosuppressants in organ transplantation. To elucidate hepatic side effects,
      we examined hepatic mRNA of proteins involved in biliary and hepatocellular
      transport of drugs, formation of glutathione (GSH) and drug metabolising
      cytochrome P-450 enzymes (CYPs) in rats treated orally for 2 weeks with
      cyclosporine A (15 mg/kg/day), sirolimus (0.4 mg/kg/day), their combination (same
      doses), or vehicle. Liver function tests (alanine aminotransferase, alkaline
      phosphatase, gamma-glutamyl transferase and bilirubin) in blood were then
      analysed as were hepatic mRNA levels of canalicular transport proteins (Mrp2,
      Bsep, Mdr1b and Mdr2), sinusoidal transport proteins (Ntcp, Oatp1 and Oatp2), GSH
      related enzymes (gamma-glutamylcysteine synthetase light (GCSlc) and heavy
      (GCShc) chain subunits and glutathione-S-transferase) and CYPs (CYP3A9, CYP1A2,
      CYP2E1 and CYP2BI/II). Cyclosporine A caused moderate cholestatic changes in
      liver enzymes, which was synergistically exacerbated by sirolimus. The data
      suggest that the underlying mechanisms behind cholestasis were not totally
      identical in the different treatment regimens. Cholestasis secondary to
      cyclosporine A could be related to reduction in mRNA expression of GSH
      synthesising enzymes and Mrp2, leading to reduced protection against oxidative
      stress and reduced bile acid-independent bile flow. After sirolimus treatment,
      Mrp2 mRNA was also reduced together with reduced levels of most CYPs and
      increased Oatp2, possibly leading to accumulation of toxic metabolites in the
      hepatocytes. The enhanced cholestatic effect of the combination treatment could
      be related to reduced GSH synthesising enzymes and even more pronounced reduction
      in Mrp2 mRNA and increase of Oatp2 mRNA.

PMID- 11589786
TI  - Biphasic effect of cardiac glycosides on action potential duration in isolated
      Purkinje fibers.
AB  - Despite the historical use of cardiac glycosides, the data describing the
      electrophysiological characteristics of this class of drug are not fully clear.
      The present study reported the biphasic effect of cardiac glycosides, digoxin
      (1.25 microM) and acetylstrophanthidin (0.15 microM), on action potential
      duration in isolated Purkinje fibers by the conventional glass microelectrode
      technique. At the cycle lengths of 990, 690 and 490 msec., action potential
      duration lengthened within 10 min. and shortened after 10 min. of digoxin and
      acetylstrophanthidin administration. The biphasic effect was observed at a
      concentration of 4.0 mM [K(+)]o. However, at a higher [K(+)]o concentration of
      5.4 mM, only the shortening effect on action potential duration was recorded.
      These results suggest that the biphasic effect of cardiac glycosides on action
      potential duration is related to the concentration of extracellular potassium and
      is not related to the stimulating cycle lengths.

PMID- 11589787
TI  - Bisphosphonates and nephrocalcinosis in a rabbit leg lengthening model: a
      histological and therapeutic comparison.
AB  - We performed a comparison of the effects of two bisphosphonates, pamidronate and
      zoledronic acid, on regenerate bone mineral content in distraction osteogenesis
      in an immature rabbit model. Single dose zoledronic acid was found to be 18 times
      more potent at producing an increase in bone mineral content than pamidronate per
      mg/kg of drug infused at surgery. Histological examination of all rabbit kidneys
      was performed at trial completion. Nephrocalcinosis was identified in 14 of 20
      kidneys of rabbits infused with pamidronate, but was not detected in the 20
      kidneys of those rabbits infused with zoledronic acid. A further 20 kidneys from
      rabbits given a second dose of zoledronic acid were also found to be free of
      signs of nephrocalcinosis. Three of 40 control kidneys exhibited signs of
      nephrocalcinosis. The increased potency of zoledronic acid allowed us to give one
      tenth the dose of pamidronate, with increased therapeutic efficacy and no
      evidence of nephrocalcinosis.

PMID- 11589789
TI  - Introduction. European STD guidelines.

PMID- 11589790
TI  - European guideline for the organization of a consultation for sexually
      transmitted diseases.

PMID- 11589791
TI  - European guideline for testing for HIV infection.

PMID- 11589792
TI  - European guideline for the management of syphilis.

PMID- 11589793
TI  - European guideline for the management of gonorrhoea.

PMID- 11589794
TI  - European guideline for the management of chlamydial infection.

PMID- 11589795
TI  - European guideline for the management of genital herpes.

PMID- 11589796
TI  - European guideline for the management of anogenital warts.

PMID- 11589798
TI  - European guideline for the management of scabies.

PMID- 11589799
TI  - European guideline for the management of pediculosis pubis.

PMID- 11589797
TI  - European guideline for the management of hepatitis B and C virus infections.

PMID- 11589800
TI  - European guideline for the management of urethritis.

PMID- 11589801
TI  - European guideline for the management of balanoposthitis.

PMID- 11589803
TI  - European guideline for the management of tropical genito-ulcerative diseases.

PMID- 11589802
TI  - European guideline for the management of vaginal discharge.

PMID- 11589804
TI  - European guideline for the management of pelvic inflammatory disease and
      perihepatitis.

PMID- 11589805
TI  - European guideline for the management of epididymo-orchitis and syndromic
      management of acute scrotal swelling.

PMID- 11589806
TI  - European guideline for the management of sexually acquired reactive arthritis.

PMID- 11589807
TI  - The legal framework covering the practice of genitourinary medicine in the UK:
      the Venereal Diseases Regulations.
AB  - The legal framework governing the practice of genitourinary medicine is traced
      from 1916 to the present. The first legislation, the Public Health (Venereal
      Diseases) Regulations of 1916 was comprehensive, and accompanied by guidance on
      setting up outpatient clinics and their supporting laboratories with practical
      advice on taking samples to support clinical diagnosis. Confidentiality was
      emphasized. The regulations led to the development of a nationwide network of
      clinics providing free care, open at times convenient to the public, and situated
      in general hospitals in large centres of population. Most of the principles still
      apply. Subsequent legislation centred on maintaining the confidentiality of all
      information obtained in relation to persons examined or treated for venereal
      disease, but allows transfer of details between healthcare providers to
      facilitate care and contact tracing. While the initial regulations stated that
      the venereal diseases were syphilis, gonorrhoea and chancroid, the legislation
      now covers all sexually transmitted diseases.

PMID- 11589808
TI  - A review of physical and psychological factors in vulvar vestibulitis syndrome.
AB  - This review is based on a MEDLINE search of all papers on vulvar vestibulitis
      syndrome (VVS) published 1995-2000. The causation, natural history and prevalence
      of VVS are unknown. There is no convincing evidence that VVS is the result of an
      infection or of an allergy. It has been proposed that it is an atypical pain
      syndrome but there is currently no clear evidence that this is so. The usual
      diagnostic criteria used in VVS are of doubtful discriminative value. Findings
      from biopsies of women with VVS are inconsistent. While there is some evidence to
      suggest that women with VVS attending clinics differ psychologically from normal
      controls, it is not clear whether these differences reflect the effects of VVS,
      are the result of patient selection or influence the development of the disease.
      Several treatments, including biofeedback, psychosexual treatment and surgery
      have been reported to be successful in some patients but there is a lack of
      proper placebo-controlled trials on which to base estimates of efficacy. There is
      a vital need for further, high-quality, research in this area.

PMID- 11589809
TI  - Behavioural assessment for HIV prevention: a model programme design.
AB  - This paper describes a model HIV prevention programme for relief agencies working
      in extremely impoverished or socially disrupted areas. A detailed behavioural
      inventory is proposed to assess: sexual behaviours, traditional cutting
      procedures, midwifery practices, the availability of injectables and injection
      equipment in local markets, the use of intoxicants, sex workers, prisons,
      military behaviours, community beliefs, and the performance of the community
      health infrastructure. The needs of AIDS orphans and the stigmatizations of
      person's with AIDS are also assessed. This assessment also examines who has
      authority to address these issues and what measures of programme assessment could
      be used for each programme area. The model is currently being tested in south
      Sudan.

PMID- 11589810
TI  - Vaginal shedding of hepatitis C virus.
AB  - A group of 14 women infected with hepatitis C virus (HCV) was evaluated for
      vaginal shedding of the virus. The HCV-RNA detection was performed in plasma,
      peripheral blood mononuclear cells (PBMC) and in supernatant and pellet of
      vaginal washings. HCV-RNA positive results were obtained in all plasma samples,
      in 57% of the PBMC samples, in 36% pellets obtained following centrifugation of
      vaginal washings and in 36% of the supernatants. In 21% of the women a positive
      result was found, at the same time, in every analysed product. The HCV genotypes
      identified in the plasma samples (1a: 38%; 1b: 36%; 3a: 13% and 1b+3a: 14%)
      matched with those in PBMC and vaginal washings in every sample, with the
      exception of cases where mixed infection (1b+3a) was detected. In these, genotype
      1b was only detected in plasma. HCV viral load was not associated with the
      presence of HCV-RNA in PBMC or in vaginal washings (either cells or supernatant).

PMID- 11589811
TI  - Imiquimod 5% cream is a safe and effective self-applied treatment for anogenital
      warts--results of an open-label, multicentre Phase IIIB trial.
AB  - Our objective was to determine the efficacy and safety of imiquimod 5% cream in
      the treatment of external genital/perianal warts in an open-label Phase IIIB
      trial. Patients applied imiquimod 5% cream 3 times per week, for up to 16 weeks.
      Those who cleared their warts were monitored during a 6-month follow-up period.
      If their warts recurred, or new warts developed during this time, patients could
      be re-treated for up to 16 additional weeks. Patients who experienced partial
      clearance during the initial treatment period entered an extended treatment
      period of up to an additional 16 weeks. A total of 943 patients from 114 clinic
      sites in 20 countries participated in this study. Complete clinical clearance was
      observed in 451/943 (47.8%) patients (intent-to-treat (ITT) analysis) during the
      initial treatment period, with clearance in an additional 52 (5.5%) patients
      during the extended treatment period beyond 16 weeks. The overall clearance rate
      for the combined treatment periods was 53.3%. In a treatment failure analysis,
      the overall clearance rate was 65.5%; a greater proportion of female patients
      (75.5%) experienced complete clearance than male patients (56.9%). Low recurrence
      rates, of 8.8% and 23.0%, were observed at the end of the 3- and 6-month follow
      up periods, respectively. The sustained clearance rates (patients who cleared
      during treatment and remained clear at the end of the follow-up period) after 3
      and 6 months were 41.6% and 33.0% (ITT analysis), respectively. Local erythema
      occurred in 67% of patients. In the majority of patients local skin reactions
      were of mild to moderate severity. In conclusion, imiquimod 5% cream is an
      effective self-applied treatment for external genital/perianal warts when applied
      for up to 16 weeks and is well tolerated for up to 32 weeks.

PMID- 11589812
TI  - Midwives and HIV antibody testing: identifying the key factors for achieving the
      targets.
AB  - A questionnaire study was designed to assess whether differences in knowledge and
      attitudes to HIV infection existed between midwives working in areas of higher
      and lower HIV prevalence, and the extent to which this influenced the uptake of
      HIV antibody testing by their clients. The response rate was 75% (219/292).
      Midwives in an area of a higher HIV prevalence had significantly greater
      experience with HIV-positive mothers, were more confident with HIV-related issues
      and were less judgemental in their attitudes than midwives in an area of lower
      HIV prevalence. However, midwives who had been offering HIV testing for more than
      2 years were significantly less likely to achieve an HIV antibody test uptake
      rate of more than 75% than those who had been offering testing for less than 2
      years, 35% (95% confidence interval [CI]: 22.2-48.6%) vs 67% (95% CI: 56.3
      76.0%), respectively. This demonstrates the need for regular updating of midwives
      about HIV antibody testing.

PMID- 11589813
TI  - What do patients attending HIV and GUM outpatient clinics want from service
      providers? Results from a large-scale consultation exercise in west London.
AB  - Our objectives were to understand patient demographic profiles, experiences of
      care and opinions about services. A questionnaire survey of 202 HIV patients and
      389 genitourinary medicine (GUM) outpatients attending clinics during one week in
      1999 was undertaken at a clinical directorate of HIV/GUM in west London. HIV and
      GUM patients differed by age (over 30: 84% vs 39%), sex (male: 88% vs 51%), and
      attendance (attended 6+ times: 55% vs 14%). Most indicated that they were
      satisfied with the general standard of care (97% HIV patients vs 95% GUM
      patients). Several clinic features were rated essential. When indicating reasons
      they might leave in the future, HIV patients were more likely to select leading
      edge care factors, such as lack of up-to-date treatment (54%). More GUM patients
      selected factors relating to convenience, such as waiting times (58%). In
      conclusion, most HIV and GUM patients were satisfied with their care, but
      differing experiences and opinions need to be addressed when planning services.

PMID- 11589815
TI  - Acceptance of syphilis screening among residents of high-STD-risk Houston
      communities.
AB  - The purpose of this study was to assess the rate of acceptance of street
      intercept syphilis screening and to identify barriers to screening among
      residents of 2 Houston communities with high rates of syphilis. Each of 691
      people who participated in a street-intercept survey about syphilis was offered a
      free syphilis test immediately after completion of the survey. Acceptors of
      screening had blood drawn at the site of the interview, and blood samples were
      tested by rapid plasma reagin (RPR) and a confirmatory microhaemagglutination
      Treponema pallidum (MHA-TP) for those with a positive antibody reaction on the
      RPR. On-street syphilis screening was accepted by 26% of the sample. The most
      common reason for refusal was not wanting to have blood drawn (19.5%). Among
      those screened for syphilis (n=148), seroprevalence was 19%, with 33% of women
      testing positive and 10% of men. The results of this study point to a need for
      increased case-finding, standard screening recommendations, and interventions
      targeting specific barriers to syphilis screening.

PMID- 11589814
TI  - High-risk behaviours in men from Bogota, Colombia and the spread of HIV.
AB  - Our objective was to identify sexual behaviours related to risk of HIV infection.
      A cluster survey of sexually experienced men from diverse sociodemographic
      settings in Bogota, Colombia was carried out using a standardized self
      administered questionnaire. A high response rate (96%) resulted in the enrollment
      of 553 men. Most participants 129/442 reported having intercourse with women and
      51/111 reported having sex with other men. Most respondents (90%) engaged in high
      risk sexual practices; only 2% knew their HIV-1 serostatus. Consistent condom use
      was reported by 20% of those who practised anal sex, and was even lower (5%)
      among men who had sex with women during menses. Heterosexuals exhibited a higher
      degree of risky sexual patterns than homosexual/bisexuals (P=0.01). In
      conclusion, high-risk sexual practices are prevalent among men in Bogota,
      particularly heterosexuals, attesting to the urgent need for effective and
      specific interventions to prevent HIV transmission.

PMID- 11589816
TI  - An audit of baseline assessment of patients with HIV infection.
AB  - A multicentre retrospective medical audit was conducted on the baseline
      investigations of new patients with HIV infection. A total of 20 investigations
      were audited for men and 21 for women. Data were received on 49 newly diagnosed
      patients infected with HIV from 8 centres in the Yorkshire region. The audit
      demonstrated that half of the patients were not screened for sexually transmitted
      infections. However, the majority of baseline assessment considered as standard
      of care, had been performed.

PMID- 11589817
TI  - Variability of the symptoms of chronic abacterial prostatitis/chronic pelvic pain
      syndrome during intermittent therapy with rectal prednisolone foam for ulcerative
      colitis.
AB  - We describe the response of symptoms of chronic abacterial prostatitis/chronic
      pelvic pain syndrome (CAP/PPS) in a man treated with rectal prednisolone for
      concomitant ulcerative colitis. The temporal relationship of the symptoms of
      CAP/PPS to starting and stopping the topical corticosteroid over 2 treatment
      cycles lends further anecdotal support to our hypothesis that treatment of the
      immune-mediated response in this chronic condition has a beneficial effect upon
      symptomatic outcome.

PMID- 11589820
TI  - Why do children attend the genitourinary medicine clinic?

PMID- 11589821
TI  - The role of NNRTIs in antiretroviral combination therapy: an introduction.
AB  - In October 2000 a meeting was convened by DuPont Pharma in Scotland to discuss
      the role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in
      antiretroviral therapy. The Round Table meeting focused on comparisons between
      efavirenz and nevirapine in clinical studies and clinical practice, and the
      manuscripts published in this supplement report the most salient points from the
      presentations and discussions.

PMID- 11589818
TI  - Syphilitic panuveitis and asymptomatic neurosyphilis: a marker of HIV infection.
AB  - Co-existing human immunodeficiency virus (HIV) infection can alter the course and
      presentation of syphilis. Severe ocular manifestations and accelerated natural
      course of syphilis along with neurosyphilis may be associated with HIV infection.
      A 30-year-old man is described in whom syphilitic panuveitis and asymptomatic
      neurosyphilis served as a marker for HIV infection.

PMID- 11589822
TI  - Comparison of NNRTIs in antiretroviral-naive patients.

PMID- 11589823
TI  - Comparison of NNRTIs in antiretroviral-experienced patients.

PMID- 11589824
TI  - Factors affecting adherence and convenience in antiretroviral therapy.

PMID- 11589825
TI  - Other issues: penetration into sanctuary sites, immune reconstitution and NNRTI
      sequencing.

PMID- 11589826
TI  - Repetitive intrathecal injections of poliovirus replicons result in gene
      expression in neurons of the central nervous system without pathogenesis.
AB  - Poliovirus-based vectors (replicons) can be used for gene delivery to motor
      neurons of the CNS. In the current study, a replicon encoding green fluorescent
      protein (GFP) was encapsidated into authentic poliovirions, using established
      procedures. Intrathecal delivery of encapsidated replicons encoding GFP to the
      CNS of mice transgenic for the human poliovirus receptor did not result in any
      functional deficits as judged by behavioral testing. Histological analysis of the
      CNS of mice given a single intrathecal injection of poliovirus replicons encoding
      GFP revealed no obvious pathogenesis in neurons (or other cell types) within the
      CNS. The expression of GFP was confined to motor neurons throughout the
      neuroaxis; a time course of expression of GFP revealed that expression was
      detectable 24 hr postinoculation and returned to background levels by 120 hr
      postinoculation. A procedure was devised to allow repetitive inoculation of
      replicons within the same animal. Behavioral testing of animals that had received
      6 to 13 independent inoculations of replicons revealed no functional deficits.
      Histological analysis of the CNS from animals that had received 6 to 13
      sequential inoculations of replicons revealed no obvious abnormalities in neurons
      or other cell types in the CNS; expression of GFP was demonstrated in neurons 24
      to 72 hr after the final inoculation of the replicon. Furthermore, there was no
      obvious inflammatory response in the CNS after the multiple inoculations. These
      studies establish the safety and efficacy of replicons for gene delivery to the
      CNS and are discussed with respect to use of replicons as new therapeutic
      strategies for spinal cord injuries and/or neurological diseases.

PMID- 11589827
TI  - High-efficiency gene transfer into rhesus macaque primary T lymphocytes by
      combining 32 degrees C centrifugation and CH-296-coated plates: effect of gene
      transfer protocol on T cell homing receptor expression.
AB  - Although steady progress has been made in transducing human T lymphocytes by
      Moloney murine leukemia virus (Mo-MuLV)-based vectors, few studies have been done
      to define ex vivo gene transfer protocols to transduce rhesus macaque primary T
      lymphocytes. Given the fact that simian immunodeficiency virus (SIV) infection in
      rhesus macaque is a well-characterized model for human immunodeficiency virus
      (HIV), it is of great interest to develop an efficient protocol to transduce
      rhesus macaque primary T cells. In this study, we have used MuLV-10A1-pseudotyped
      retrovirus expressing enhanced green fluorescent protein (EGFP) to evaluate a
      number of ex vivo gene transfer protocols in rhesus macaque primary T
      lymphocytes. Our objectives in designing these protocols were (1) to test whether
      higher efficiency gene transfer could be obtained by combining two previously
      defined protocols, centrifugation at 32 degrees C and the CH-296-coated plate;
      and (2) to study the effect of an ex vivo gene transfer protocol on the
      expression of lymphocyte homing receptors L-selectin and alpha 4 beta 7 and alpha
      4 beta 1 integrins. From seven independent experiments we demonstrate by flow
      cytometry analyses of EGFP expression that whereas centrifugation at 32 degrees C
      or the fibronectin fragment CH-296-coated plate protocol alone yielded 10-14%
      transduction efficiency, combining these two protocols resulted in 28.1-51.2%
      transduction efficiency. EGFP in transduced cells was expressed highly throughout
      the 14 days of posttransduction expansion. Our results also demonstrate that
      whereas the transduction procedure per se did not significantly alter the
      expression of lymphocyte homing receptors, anti-CD3 and anti-CD28 antibody
      stimulation profoundly reduced the expression of L-selectin. The selective
      reduction of L-selectin may result in significant in vivo consequences if
      transduced cells are infused.

PMID- 11589828
TI  - In utero gene delivery by intraamniotic injection of a retroviral vector producer
      cell line in a nonhuman primate model.
AB  - In utero gene therapy (IUGT) offers the promise of treating a wide variety of
      genetic diseases before the development of disease manifestations. The most
      convenient and potentially easiest method of targeting the fetus is through
      injection into the amniotic cavity. For long-term correction of genetic defects,
      retroviral vectors have great potential as a tool for gene therapy strategies.
      However, retroviral vectors are limited by growth to low titers. In an attempt to
      increase the amount of vector particles delivered and assess the potential of
      intraamniotic administration, we injected a retroviral vector producer cell line
      encoding the lacZ gene into the amniotic fluid of a nonhuman primate model. After
      birth the infants were analyzed for vector-mediated transduction. Two of four
      fetuses were successfully transduced, with transgene expression detected in the
      esophagus, trachea, and stomach. In some sections of tissue, nearly 100% of the
      cells lining the lumen of these tissues were positive for transduction. Although
      successful, the limited number of tissues in which transduction was observed led
      to an in vitro analysis of the effects of amniotic fluid (AF). The presence of
      amniotic fluid inhibited transduction by 99%. AF affected both the transducing
      activity of the vector and the health of the packaging cells. The negative
      effects of AF were gestational age dependent; greater inhibition was observed
      from AF collected at later stages of pregnancy. The fact that transduction was
      successful despite these negative effects indicates that this approach is a
      promising strategy for gene therapy.

PMID- 11589829
TI  - Dendritic cells transduced with HSV-1 amplicons expressing prostate-specific
      antigen generate antitumor immunity in mice.
AB  - There is currently much interest in generating cytotoxic T lymphocyte (CTL)
      responses against tumor antigens as a therapy for cancer. This work describes a
      novel gene transfer technique utilizing dendritic cells (DCs), an extremely
      potent form of antigen-presenting cell (APC), and herpes simplex virus-1 (HSV-1)
      amplicons. HSV-1 amplicons are plasmid-based viral vectors that are packaged into
      HSV-1 capsids, but lack viral coding sequences. Amplicon vectors have been
      constructed that encode the model tumor antigen ovalbumin (HSV-OVA) and human
      prostate-specific antigen (HSV-PSA), a protein that is expressed specifically in
      prostate epithelium and prostate carcinoma cells. These amplicons were packaged
      using a helper virus-free system that produces vector stocks that are devoid of
      contaminating cytotoxic helper virus. Transduction of DCs with HSV-OVA or HSV-PSA
      and co-culture with CTL hybridomas results in specific activation, indicating
      that transduced DCs express these transgenes and process the tumor antigens for
      class I MHC presentation to CTL. Mice immunized with HSV-PSA-transduced DCs
      generate a specific CTL response that can be detected in vitro by a (51)Cr
      release assay and are protected from challenge with tumors that express PSA.
      These results indicate that DCs transduced with HSV-1 amplicon vectors may
      provide a tool for investigation of the biology of CTL activation by DCs and a
      new modality for immunotherapy of cancer.

PMID- 11589831
TI  - Systematic determination of the packaging limit of lentiviral vectors.
AB  - Because of their ability to transduce nondividing cells, human immunodeficiency
      virus type 1 (HIV)-based vectors have great potential for the therapeutic
      delivery of genes to cells. We describe here a systematic study of the packaging
      limit of HIV-based vectors. Restriction endonuclease-generated bacterial
      chromosomal DNA fragments of different lengths were cloned at three different
      positions within a lentiviral vector. Vesicular stomatitis virus G protein (VSV
      G) pseudotyped lentiviral particles were prepared and the different clones were
      titered on mammalian cells. We observed that the restriction endonuclease site
      positions at the 5' and 3' ends of the genome were superior with regard to
      insertional capacity of foreign DNA. In all cases, viral titers decreased semi
      logarithmically with increasing vector length. There appears to be no absolute
      packaging limit because measurable titers were obtained even when the proviral
      length was in excess of 18 kb. The reduction in titer appears to occur at the
      level of viral encapsidation, although we cannot exclude limitations in nuclear
      export of proviral RNA. These results suggest that HIV-based vectors may have a
      secondary advantage over oncoretroviral vectors because of their greater
      packaging limit, although the very low titers of the larger vectors will be of
      limited utility.

PMID- 11589830
TI  - Enhancing T cell activation and antiviral protection by introducing the HIV-1
      protein transduction domain into a DNA vaccine.
AB  - Protein transduction domains (PTD), which can transport proteins or peptides
      across biological membranes, have been identified in several proteins of viral,
      invertebrate, and vertebrate origin. Here, we evaluate the immunological and
      biological consequences of including PTD in synthetic peptides and in DNA
      vaccines that contain CD8(+) T cell epitopes from lymphocytic choriomeningitis
      virus (LCMV). Synthetic PTD-peptides did not induce detectable CD8(+) T cell
      responses. However, fusion of an open reading frame encoding a PTD to an epitope
      minigene caused transfected tissue culture cells to stimulate epitope-specific T
      cells much more effectively. Kinetic studies indicated that the epitope reached
      the surface of transfected cells more rapidly and that the number of transfected
      cells needed to stimulate T cell responses was reduced by 35- to 50-fold when
      compared to cells transfected with a standard minigene plasmid. The mechanism
      underlying the effect of PTD linkage is not clear, but transit of the PTD
      attached epitope from transfected cells to nontransfected cells (cross
      presentation) seemed to play, at most, a minimal role. Mice immunized once with
      the plasmid encoding the PTD-linked epitope showed a markedly accelerated CD8(+)
      T cell response and, unlike mice immunized with a standard plasmid, were
      completely protected against a normally lethal LCMV challenge administered only 8
      days post-immunization.

PMID- 11589833
TI  - Preexposure efficacy of a novel combination DNA and inactivated rabies virus
      vaccine.
AB  - Several strategies are being examined to enhance the potency of DNA rabies
      vaccine (DRV) so that it can be used for both prophylaxis and postexposure
      therapy of rabies. In this study, we report a novel combination rabies vaccine
      (CRV) containing a low dose of cell culture-derived inactivated rabies virus
      vaccine and DRV. Mice immunized with CRV develop higher levels of rabies virus
      neutralizing antibodies (RVNA) than those immunized with DRV and are completely
      protected against peripheral as well as intracerebral rabies virus challenge. The
      quantity of inactivated rabies virus vaccine required for enhancing the potency
      of DRV can be 625-fold lower than that of a standard dose of inactivated rabies
      virus vaccine. CRV induces higher levels of RVNA than DRV in cattle as well.
      Thus, we demonstrate for the first time that co-inoculation of DNA vaccine and a
      low dose of inactivated virus vaccine can be developed into a novel cost
      effective vaccination strategy for combating rabies in particular, and infectious
      diseases in general.

PMID- 11589832
TI  - A phase I study of aerosolized administration of tgAAVCF to cystic fibrosis
      subjects with mild lung disease.
AB  - Cystic fibrosis (CF) is one of the most common autosomal recessive disorders in
      North America, leading to significant morbidity and early mortality. The defect
      in the cystic fibrosis transmembrane conductance regulator protein (CFTR)
      function can be corrected in vitro by gene replacement with a wild-type gene. A
      Phase I, single administration, dose escalation trial was designed and executed
      to assess safety and delivery of tgAAVCF, an adeno-associated virus (AAV) vector
      encoding the human CFTR cDNA, by nebulization to the lungs of CF subjects. Four
      cohorts of three subjects each were administered increasing doses of the study
      agent, beginning with 10(10) DNase-resistant particles (DRP) and escalating in
      log increments up to 10(13) DRP. Sequential bronchoscopies were performed to
      gather analytical samples throughout the study. All 12 subjects completed the
      study. There were a total of 242 adverse events (AEs), six of which were defined
      as serious and three of which were defined as possibly being related to the study
      drug. A clear dose-response relationship was observed in vector gene transfer. A
      maximum of 0.6 and 0.1 vector copies per brushed cell were observed 14 days and
      30 days, respectively, following nebulization of 10(13) DRP tgAAVCF, and this
      declined to nearly undetectable levels by day 90. Vector gene transfer was evenly
      distributed throughout the fourth airway generation following single-dose
      administration. RNA-specific PCR did not detect vector-derived mRNA. This Phase I
      trial shows that aerosolized tgAAVCF is safe and widely delivered to the proximal
      airways of CF subjects by nebulization.

PMID- 11589837
TI  - Differences in the diagnosis of myocardial infarction by troponin T compared with
      clinical and epidemiologic criteria.
AB  - We investigated the difference in the number of myocardial infarction (MI)
      diagnoses based on troponin T compared with clinical and epidemiologic (modified
      FINnish Multinational MONItoring of trends and determinants in CArdiovascular
      diseases) diagnoses, and the prognosis of patients with discordant diagnoses.
      Five hundred fifty-nine consecutive patients (315 men and 244 women, median age
      69 years) were admitted to the hospital with a suspected acute coronary syndrome.
      Median follow-up time was 17 months. Of the 559 patients, 127 had a clinical and
      137 an epidemiologic diagnosis of MI. When a diagnosis of MI was primarily based
      on troponin T (>0.10 microg/L), the number of MIs was 169, which increased by 33%
      compared with the number of MIs by clinical diagnosis, and by 23% compared with
      those by epidemiologic diagnosis. However, troponin T was not elevated in 13% of
      the 127 patients with the clinical diagnosis and in 14% of the 137 patients with
      the epidemiologic diagnosis of MI. Among patients in whom clinical diagnosis of
      MI was not made, the prognosis with regard to coronary death or nonfatal MI was
      not significantly worse in patients with troponin T >0.10 microg/L than < or
      =0.10 microg/L (hazard ratio 1.07; 95% confidence interval 0.62 to 1.84). In
      patients with a suspected acute coronary syndrome, troponin T-based diagnostics
      leads to an increase in the number of patients diagnosed with MI compared with
      clinical or epidemiologic diagnosis. The prognostic impact of troponin T in
      patients without clinical diagnosis of MI based on elevations in conventional
      enzyme activities needs further study in larger series of patients.

PMID- 11589834
TI  - Empty capsids in column-purified recombinant adenovirus preparations.
AB  - Empty capsids from adenovirus, that is, virus particles lacking DNA, are well
      documented in the published literature. They can be separated from complete virus
      by CsCl density gradient centrifugation. Here we characterize the presence of
      empty capsids in recombinant adenovirus preparations purified by column
      chromatography. The initial purified recombinant adenovirus containing the p53
      tumor suppressor gene was produced from 293 cells grown on microcarriers and
      purified by passage through DEAE-Fractogel and gel-filtration chromatography.
      Further sequential purification of the column-purified virus by CsCl and glycerol
      density gradient centrifugations yielded isolated complete virus and empty
      capsids. The empty capsids were essentially noninfectious and free of DNA.
      Analysis of empty capsids by SDS-PAGE or RP-HPLC showed the presence of only
      three major components: hexon, IIIa, and a 31K band. This last protein was
      identified as the precursor to protein VIII (pVIII) by mass spectrometric
      analysis. No pVIII was detected from the purified complete virus. Analysis by
      electron microscopy of the empty capsids showed particles with small defects. The
      amount of pVIII was used to determine the level of empty capsid contamination.
      First, the purified empty capsids were used to quantify the relation of pVIII to
      empty capsid particle concentration (as estimated by either light scattering or
      hexon content). They were then used as a standard to establish the empty capsid
      concentration of various recombinant adenovirus preparations. Preliminary
      research showed changes in empty capsid concentration with variations in the
      infection conditions. While virus purification on anion-exchange or gel
      filtration chromatography has little effect on empty capsid contamination, other
      chromatographic steps can substantially reduce the final concentration of empty
      capsids in column-purified adenovirus preparations.

PMID- 11589836
TI  - Association of serum apolipoprotein A-I (but not high-density lipoprotein
      cholesterol) with healed myocardial infarction in men independent of serum
      insulin and C-peptide.
AB  - Low serum levels of high-density lipoprotein (HDL) cholesterol or apolipoprotein
      A-I and high serum levels of insulin increase the risk of coronary heart disease
      (CHD) and can indicate insulin resistance. We tested the strength, independence,
      and interactions of associations between HDL cholesterol (or apolipoprotein A-I),
      insulin (or C-peptide), glucose, and CHD in 95 male nondiabetic patients with CHD
      who were <60 years old, in 92 probands from the PROCAM study, and in 61 non
      cardiologic patients; all subjects were matched by age, body mass index, and
      smoking habits. Systemic hypertension (odds radio [OR] 2.8, 95% confidence
      intervals [CI] 1.6 to 4.8), high serum levels of glucose (OR 2.3, 95% CI 1.6 to
      4.8), insulin (OR 2.1, 95% CI 1.3 to 3.6), and C-peptide (OR 4.1, 95% CI 2.2 to
      7.5) as well as low serum levels of HDL cholesterol (OR 2.0, 95% CI 1.1 to 3.5)
      or apolipoprotein A-I (OR 3.9, 95% CI 2.1 to 7.1) had significant associations
      with CHD. At multivariate analysis, systolic blood pressure, glucose,
      apolipoprotein A-I, and C-peptide, but not HDL cholesterol and insulin, had
      consistent independent associations with CHD. Thus, the combined measurement of
      apolipoprotein A-I and C-peptide may improve the identification of nondiabetic
      patients at increased risk for CHD.

PMID- 11589838
TI  - Impact of troponin T determinations on hospital resource utilization and costs in
      the evaluation of patients with suspected myocardial ischemia.
AB  - The evaluation and triage of patients with suspected myocardial ischemia in the
      emergency department remains challenging and costly. Previous studies of cardiac
      troponins have focused predominantly on patients with chest pain and have not
      randomized patients to different diagnostic strategies. Eight hundred fifty-six
      patients with suspected myocardial ischemia were prospectively randomized to
      receive a standard evaluation, including serial electrocardiographic and creatine
      phosphokinase-MB determinations (controls) or a standard evaluation with the
      addition of serial troponin T determinations (troponin group). The primary end
      points were length of stay and hospital charges. Significant reductions in length
      of hospital stay were seen in troponin T patients both with (3.6 vs 4.7 days; p =
      0.01) and without (1.2 vs 1.6 days; p = 0.03) acute coronary syndromes compared
      with controls. Total hospital charges were reduced in a similar fashion in
      troponin patients with and without acute coronary syndromes ($15,004 vs $19,202;
      p = 0.01, and $4,487 vs $6,187; p = 0.17, respectively) compared with controls.
      Troponin patients without acute coronary syndromes had fewer hospital admissions
      (25% vs 31%; p = 0.04), whereas troponin patients with acute coronary syndromes
      had shorter telemetry and coronary care unit lengths of stay (3.5 vs 4.5 days; p
      = 0.03) compared with controls. Thus, utilization of troponin T in a broad
      spectrum of emergency department patients with suspected myocardial ischemia
      improves hospital resource utilization and reduces costs.

PMID- 11589840
TI  - Clinical performance of a specific algorithm to reconfirm self-terminating
      ventricular arrhythmias in current implantable cardioverter-defibrillators.
AB  - Inappropriate shock therapy is a frequent problem in patients with implantable
      cardioverter-defibrillators (ICDs), caused mostly by supraventricular rhythms.
      Self-terminating ventricular arrhythmias (STVAs), however, may also lead to
      inappropriate shock discharges even in ICDs with abortive shock capabilities. The
      aim of this study was to evaluate the clinical performance of a specific
      ventricular tachycardia/ventricular fibrillation (VT/VF) reconfirmation algorithm
      implemented in current ICD devices from Medtronic to prevent inappropriate shock
      discharges due to STVAs. A total of 161 STVA episodes were documented in 59 of
      150 patients (39%) within a mean follow-up of 30 +/- 20 months and resulted in 25
      inappropriate shock discharges in 15 of 150 patients (10%) despite activation of
      the reconfirmation algorithm. The first synchronization interval of the algorithm
      was met in 92% of STVA episodes with and even 38% of STVA episodes without shock
      delivery. A reduced incidence of inappropriate shocks due to STVAs was found with
      tachycardia/fibrillation detection intervals (TDI/FDI) programmed to shorter
      cycle lengths < or =280 ms or the use of the first 2 cycles after the end of
      charging to be considered for reconfirmation only. Thus, inappropriate shocks due
      to STVAs still occur in 10% of patients with ICDs despite activation of a
      specific VT/VF reconfirmation algorithm, and are mainly caused by meeting the
      first synchronization interval that therefore should be shortened in cycle
      length. Moreover, to reduce the likelihood of inappropriate shocks, the VF
      reconfirmation algorithm should be optimized by basing the synchronization
      intervals exclusively on the FDI with short cycle lengths or using the first 2
      cycles for reconfirmation only.

PMID- 11589839
TI  - Efficacy of cholesterol levels and ratios in predicting future coronary heart
      disease in a Chinese population.
AB  - In this study, we assessed the efficacy of various lipid and lipoprotein
      measurements at baseline for predicting the risk for coronary heart disease (CHD)
      and determined the associated risk of CHD in subgroups stratified by different
      lipid and lipoprotein screening strategies to evaluate the adequacy of current
      total and low-density lipoprotein (LDL) cholesterol-based approaches in lipid
      management. We analyzed data from the Chin-Shan Community Cardiovascular Cohort
      study, a Chinese population-based prospective cohort study that began in 1990.
      During an 8-year follow-up period, 213 of 3,159 participants (6.7%) without CHD
      (aged > or =35 years) developed CHD. The total cholesterol/high-density
      lipoprotein (HDL) cholesterol ratio was the most powerful lipoprotein predictor
      of future CHD (hazard ratio 1.21 for a 1.0 increment in ratio; p <0.001).
      Subjects with "high-risk" LDL cholesterol levels (>160 mg/dl) and low total
      cholesterol/HDL cholesterol ratios (< or =5) had an incidence of CHD similar to
      those with low levels of both LDL cholesterol (< or =130 mg/dl) and total
      cholesterol/HDL cholesterol ratios (4.9% vs 4.6%). In contrast, subjects with
      "low-risk" LDL cholesterol levels (< or =130 mg/dl) and high total
      cholesterol/HDL cholesterol ratios (>5) had a 2.5-fold higher incidence of CHD
      than those with similar LDL cholesterol levels but low total cholesterol/HDL
      cholesterol ratios (p <0.001). Compared with using an LDL cholesterol level of
      130 mg/dl as the cut-off point, using a total cholesterol/HDL cholesterol ratio
      of 5 was associated with superior specificity (73% vs 59%, p <0.001) and accuracy
      (72% vs 58%, p <0.001), and similar sensitivity (50% vs 53%). Our data indicate
      that current guidelines for lipid management may misclassify subjects with high
      levels of HDL and LDL cholesterol as well as those with low levels of HDL and LDL
      cholesterol. Using the ratio of total to HDL cholesterol as the initial screening
      tool can obviate this discrepancy.

PMID- 11589841
TI  - Long-term infection rates associated with the pectoral versus abdominal approach
      to cardioverter- defibrillator implants.
AB  - Infection is an uncommon (0% to 6.7%) but serious complication after implantable
      cardioverter-defibrillator (ICD) implantation. All ICD primary implants,
      replacements, or revisions performed at the Massachusetts General Hospital
      between April 1983 and May 1999 were reviewed. A total of 21 ICD-related
      infections (1.2%) were identified among 1,700 procedures affecting 1.8% of the
      1,170 patients who underwent a primary implant, a generator change, or a revision
      of their systems. The mean follow-up time was 35 +/- 33 months. Of the 959
      patients with long-term follow-up, 19 of the 584 patients (3.2%) with abdominal
      and 2 of the 375 patients (0.5%) with pectoral systems developed ICD-related
      infections (p = 0.03). There was no significant difference between the infection
      rate among the 959 primary ICD implants and the 447 replacements or system
      revisions. Only 5 of the patients (24%) had systemic signs of infection,
      including fever (T>100.5) and elevated white blood count >12,000. Cultures from
      the wound revealed staphylococcal species in 16 patients (76%). Nineteen patients
      were treated with removal of the entire ICD system in addition to intravenous
      antibiotics for 2 to 4 weeks. A decrease in the incidence of ICD-related
      infection has occurred since the advent of transvenous pectoral systems. The main
      organism responsible for ICD infection is Staphylococcus. The mainstay of ICD
      infection management consists of complete removal of the entire implanted system.

PMID- 11589842
TI  - Immediate and six-month results of the profile of the Amplatzer septal occluder
      as assessed by transesophageal echocardiography.
AB  - Catheter closure of secundum atrial septal defect (ASD) using the Amplatzer
      septal occluder (ASO) is a potential alternative for open surgical repair.
      However, the large profile of the device obtained immediately after closure
      continues to raise some concerns regarding its long-term safety. To evaluate the
      changes in the profile of the device after being deployed, transesophageal
      echocardiography was performed in 70 patients (17 men and 53 women) who underwent
      catheter closure of ASDs immediately after and at 6-month follow-up. The median
      age at closure was 16 years (range 1.9 to 75) and the median size of the ASD as
      assessed by transesophageal echocardiography was 14 mm (range 3 to 25). The
      thickness (profile) of the device was assessed in the 4-chamber, short- and long
      axis views of the interatrial septum, and measured at its middle and at the
      junction of the waist with the disc at its 2 ends. Seventy-three devices were
      deployed in the 70 patients. The median size of the device was 19 mm (range 8 to
      34). Complete closure was achieved in 81.4% and 91.4% immediately after and at 6
      months follow-up, respectively. The thickness of the device at its middle
      decreased from 12.2 +/- 4.3, 12.2 +/- 3.7, and 12.5 +/- 4.3 mm in the 4-chamber,
      short- and long-axis views to 6.5 +/- 2.0, 6.3 +/- 1.9, and 6.5 +/- 2.2 mm,
      respectively. The thickness of the device at its superior, inferior, anterior,
      and posterior edges also decreased by 41.8% +/- 14.0% to 43.7% +/- 9.8%. The
      changes in the thickness were related to device size. Larger devices were thicker
      after being deployed. We conclude that the thickness of the ASO decreases by 42%
      to 48% within 6 months after deployment, resulting in a lower profile.

PMID- 11589843
TI  - Cardiovascular safety of sublingual apomorphine in patients on stable doses of
      oral antihypertensive agents and nitrates.
AB  - Sublingual (SL) apomorphine (2 to 6 mg) has been shown to be effective for
      treatment of male erectile dysfunction. Many patients with erectile dysfunction
      are also being treated for systemic hypertension and/or cardiovascular disease.
      In a double-blind, randomized, placebo-controlled, crossover trial, SL
      apomorphine 5 mg and placebo were administered on alternate days to 162 men who
      were on long-term therapy (> or =4 weeks) with angiotensin-converting enzyme
      inhibitors, beta blockers, diuretics, calcium channel blockers, alpha(1)
      blockers, or short- or long-acting nitrates. Blood pressure and heart rate were
      measured before and after dosing; cardiac rhythm was recorded by 4-hour Holter
      monitoring. The only potentially clinically significant interactions between SL
      apomorphine and the antihypertensive agents or short-acting nitrates were greater
      orthostatic decreases in systolic blood pressure in the alpha-blocker and calcium
      channel blocker groups (-10 and -6 mm Hg vs placebo, respectively).
      Administration of SL apomorphine after dosing with long-acting nitrates resulted
      in significant decreases in blood pressure when patients were standing (mean
      systolic change, -5 to -9 mm Hg 30 to 60 minutes postdose, p <0.05; mean
      diastolic change, -3 to -4 mm Hg 50 to 60 minutes postdose, p <0.05). The most
      common adverse events with SL apomorphine were dizziness, nausea, and headache.
      Syncope occurred in 1 patient in the beta-blocker group; symptomatic hypotension
      occurred in 2 patients each in the short- and long-acting nitrate groups. Thus,
      in patients receiving common antihypertensive agents and short-acting nitrates,
      as well as in most patients receiving long-acting nitrates, SL apomorphine at
      higher than recommended doses produced no clinically significant changes in heart
      rate or blood pressure greater than changes seen with SL apomorphine alone.

PMID- 11589844
TI  - Evidence-based prescription drug coverage.

PMID- 11589846
TI  - Relation between albumin in the urine and electrocardiographic markers of
      myocardial ischemia in patients without diabetes mellitus.

PMID- 11589845
TI  - Evaluation of sex-related differences in survival after hospitalization for acute
      myocardial infarction.

PMID- 11589847
TI  - Elevation of plasma level of macrophage migration inhibitory factor in patients
      with acute myocardial infarction.

PMID- 11589848
TI  - Fractal and complexity measures of heart rate dynamics after acute myocardial
      infarction.

PMID- 11589849
TI  - Predictors of quality of life following acute coronary syndromes.

PMID- 11589850
TI  - Association of arterial expansion (expansive remodeling) of bifurcation lesions
      determined by intravascular ultrasonography with unstable clinical presentation.

PMID- 11589851
TI  - Twelve-month outcome after coronary stent implantation without predilatation.

PMID- 11589852
TI  - Investigation of aortocoronary artery bypass grafts by multislice spiral computed
      tomography with electrocardiographic-gated image reconstruction.

PMID- 11589854
TI  - Effect of anticoagulation on the occurrence of deep venous thrombosis associated
      with temporary transvenous femoral pacemakers.

PMID- 11589853
TI  - Effect of atrial septal pacing on P-wave duration dispersion and atrial late
      potentials in patients with paroxysmal atrial fibrillation.

PMID- 11589856
TI  - Effect of aerobic exercise training on plasma levels of tumor necrosis factor
      alpha in patients with heart failure.

PMID- 11589855
TI  - Effective dose and cardiovascular effects of cilazapril in children with heart
      failure.

PMID- 11589857
TI  - Survey of current practices in use of amiodarone and implantable cardioverter
      defibrillators in pediatric patients with end-stage heart failure.

PMID- 11589859
TI  - Troponin levels in patients with amyloid cardiomyopathy undergoing cardiac
      transplantation.

PMID- 11589858
TI  - The site of mitral valve prolapse is a predictor of atrial fibrillation.

PMID- 11589860
TI  - Difficulty in diagnosing double-chambered right ventricle in adults.

PMID- 11589861
TI  - Transesophageal echocardiography in patients with recent stroke and normal
      carotid arteries.

PMID- 11589862
TI  - Relation of pulmonary arterial diastolic and mean pulmonary arterial wedge
      pressures in patients with and without pulmonary hypertension.

PMID- 11589864
TI  - Apparent misplacement of chest electrode on left leg: a unique example of
      electrodal confusion.

PMID- 11589863
TI  - Role of tumor necrosis factor-alpha and interleukin-6 in the effects of hormone
      replacement therapy and raloxifene on C-reactive protein in postmenopausal women.

PMID- 11589865
TI  - Interferon beta-1a for optic neuritis patients at high risk for multiple
      sclerosis.
AB  - PURPOSE: To evaluate the effect of treatment with interferon beta-1a (Avonex)
      initiated at the time of a first episode of optic neuritis in patients at high
      risk for multiple sclerosis (MS). DESIGN: Randomized clinical trial. METHODS:
      Prospective. SETTING: Fifty clinical centers throughout the US and Canada. STUDY
      POPULATION: After the onset of a first episode of optic neuritis treated with
      intravenous and oral corticosteroids, 192 patients with brain magnetic resonance
      imaging (MRI) evidence of subclinical demyelination were randomly assigned to
      receive weekly intramuscular injections of 30 microg interferon beta-1a or
      placebo. MAIN OUTCOME MEASURE: The study outcomes were the development of
      clinically definite MS within 3 years of follow-up and brain MRI changes at 6,
      12, and 18 months. RESULTS: The rates of clinically definite MS and of a combined
      MS/MRI outcome were lower in the interferon beta-1a group than in the placebo
      group (adjusted rate ratios 0.58, 95% confidence interval 0.34 to 1.00; and 0.50,
      95% confidence interval 0.34 to 0.73, respectively). Compared with the placebo
      group, on the 18-month brain MRI the interferon beta-1a group had a smaller
      change from baseline in T2 lesion volume (P =.02), fewer new or enlarging T2
      lesions (P <.001), and a lower frequency of Gd-enhancing lesions (P <.001).
      CONCLUSION: The clinical and brain MRI results of this trial support initiating
      interferon beta-1a treatment at the time of a first episode of optic neuritis
      occurring in patients at high risk for MS based on the presence of subclinical
      brain MRI lesions.

PMID- 11589867
TI  - Effects of latanoprost and unoprostone when used alone or in combination for open
      angle glaucoma.
AB  - PURPOSE: To evaluate the effects of latanoprost and unoprostone on the
      intraocular pressure (IOP) and on the tonographic outflow facility in glaucoma
      patients when used alone or in combination. DESIGN: Open label randomized
      clinical study. METHODS: Fifty-two patients (52 eyes) with primary open-angle
      glaucoma were randomly divided into two groups. One group initially received only
      latanoprost 0.005% once daily and the other group, only unoprostone 0.12% twice
      daily. The study period was 12 weeks: in the first 6 weeks, latanoprost or
      unoprostone was given as monotherapy, and in the last 6 weeks, patients received
      both drugs. IOP was measured every 2 weeks by one investigator masked to the
      medication received by patients during the study period in the same hour as on
      the baseline day. At Weeks 0, 6, and 12, the coefficient of aqueous outflow was
      measured by tonography. RESULTS: With latanoprost monotherapy, the baseline IOP
      of 22.9 +/- 2.4 mm Hg (mean +/- SD) decreased to 16.9 +/- 2.1 mm Hg (P<.01). When
      unoprostone was added to latanoprost, the IOP remained at 16.7 +/- 2.5 mm Hg.
      With unoprostone monotherapy, the baseline IOP of 22.7 +/- 2.1 mm Hg decreased to
      19.4 +/- 2.4 mm Hg (P<.01). When latanoprost was added to unoprostone, the IOP
      decreased to 16.8 +/- 1.7 mm Hg (P<.01). There was no significant change in the
      coefficient of aqueous outflow with monotherapy or the combined use of the drugs.
      CONCLUSIONS: The combination of latanoprost and unoprostone does not result in a
      more potent hypotensive effect than latanoprost alone.

PMID- 11589868
TI  - Effect of dorzolamide timolol combination versus timolol 0.5% on ocular bloodflow
      in patients with primary open-angle glaucoma.
AB  - PURPOSE: Addition of dorzolamide to timolol in primary open-angle glaucoma shows
      augmented reduction of intraocular pressure. It is unknown as yet if addition of
      dorzolamide will alter hemodynamics. METHODS: Fifteen patients with primary open
      angle glaucoma were placed on a medication-dependent 1-week to 4-week washout
      that included maintenance on timolol. After washout, baseline measurements were
      taken (timolol). They were studied after a month on timolol or dorzolamide
      timolol (Cosopt; Merck, Inc, Whitehouse Station, New Jersey), with the second
      drug preceded by another month of timolol maintenance and second baseline
      measurements. At each visit, visual function, intraocular pressure, and ocular
      hemodynamics were monitored, including indocyanine green and fluorescein
      angiography and color Doppler imaging. RESULTS: Cosopt significantly reduced
      intraocular pressure (14.7 to 13.4 mm Hg, P <.05) and increased arteriovenous
      passage time (superior temporal artery) of fluorescein dye (2.13 to 1.76 seconds,
      P =.01) but had no effect on visual function. CONCLUSIONS: When compared with
      timolol in primary open-angle glaucoma, Cosopt augments ocular tension reduction
      and reduces the amount of time required for blood to pass through the superior
      retinal vasculature.

PMID- 11589866
TI  - Travoprost compared with latanoprost and timolol in patients with open-angle
      glaucoma or ocular hypertension.
AB  - PURPOSE: This study evaluated the safety and intraocular pressure-lowering
      efficacy of two concentrations of travoprost (0.0015% and 0.004%) compared with
      latanoprost 0.005% and timolol 0.5% in patients with open-angle glaucoma or
      ocular hypertension. METHODS: Eight hundred one patients with open-angle glaucoma
      or ocular hypertension were randomly assigned to travoprost 0.0015%, travoprost
      0.004%, latanoprost 0.005%, or timolol 0.5%. The efficacy and safety of
      travoprost (0.0015% and 0.004%) daily was compared with latanoprost daily and
      timolol twice daily for a period of 12 months. RESULTS: Travoprost was equal or
      superior to latanoprost and superior to timolol with mean intraocular pressure
      over visits and time of day ranging from 17.9 to 19.1 mm Hg (travoprost 0.0015%),
      17.7 to 19.1 mm Hg (travoprost 0.004%), 18.5 to 19.2 mm Hg (latanoprost), and
      19.4 to 20.3 mm Hg (timolol). For all visits pooled, the mean intraocular
      pressure at 4 PM for travoprost was 0.7 mm Hg (0.0015%, P =.0502) and 0.8 mm Hg
      (0.004%, P =.0191) lower than for latanoprost. Travoprost 0.004% was more
      effective than latanoprost and timolol in reducing intraocular pressure in black
      patients by up to 2.4 mm Hg (versus latanoprost) and 4.6 mm Hg (versus timolol).
      Based on a criterion of 30% or greater intraocular pressure reduction from
      diurnal baseline or intraocular pressure 17 mm Hg or less, travoprost 0.0015% and
      0.004% had an overall response to treatment of 49.3% and 54.7%, respectively,
      compared with 49.6% for latanoprost and 39.0% for timolol. Iris pigmentation
      change was observed in 10 of 201 of patients (5.0%) receiving travoprost 0.0015%,
      six of 196 of patients (3.1%) receiving travoprost 0.004%, 10 of 194 of patients
      (5.2%) receiving latanoprost, and none of the patients receiving timolol (0 of
      196). The average ocular hyperemia score was less than 1 on a scale of 0 to 3,
      indicating that on average patients experienced between none/trace and mild for
      all treatment groups. There were no serious, unexpected, related adverse events
      reported for any therapy. CONCLUSIONS: Travoprost (0.0015% and 0.004%), a highly
      selective, potent prostaglandin F (FP) receptor agonist, is equal or superior to
      latanoprost and superior to timolol in lowering intraocular pressure in patients
      with open-angle glaucoma or ocular hypertension. In addition, travoprost 0.004%
      is significantly better than either latanoprost or timolol in lowering
      intraocular pressure in black patients. Travoprost is safe and generally well
      tolerated in the studied patient population.

PMID- 11589869
TI  - Influence of surgical reduction of intraocular pressure on regions of the visual
      field with different levels of sensitivity.
AB  - PURPOSE: To determine whether the ability to document improvement in visual
      fields after intraocular pressure (IOP) reduction can be enhanced by focusing on
      regions of the field with different levels of sensitivity. DESIGN: Cohort study.
      METHODS: This is a retrospective study. SETTING: Yale Eye Center. STUDY
      POPULATION: The visual fields (Octopus G2) of 30 eyes of 30 patients undergoing
      trabeculectomy. OBSERVATION PROCEDURE: Visual fields were evaluated a mean of
      three months before and 7.8 months after surgery. MAIN OUTCOME MEASURES: Change
      in sensitivity between the preoperative and postoperative visual fields (Delta S)
      was evaluated globally by comparing all 59 points of sensitivity and regionally
      in three groups according to preoperative sensitivity (pre-S): 25% of highest,
      50% intermediate, and 25% of lowest points of sensitivity. Improvement in Delta S
      was also correlated with preoperative mean defect (pre-MD), percent intraocular
      pressure (IOP) reduction (Delta IOP%), and patient's age. RESULTS: Six visual
      fields showed improvement in Delta S when evaluated globally and nine showed
      improvement in pre-S subgroups. Of the latter, all nine showed improvement in the
      subgroup with the lowest pre-S, and two in the intermediate subgroup, but none in
      the subgroup with the highest pre-S. Combining the subgroups with the lowest pre
      S and the highest Delta IOP% was associated with the highest mean Delta S.
      CONCLUSION: The ability to document improvement in visual fields following
      surgical reduction of IOP may be enhanced by focusing on subgroups of test points
      with lower baseline sensitivity.

PMID- 11589870
TI  - Relationship between visual field testing and scanning laser polarimetry in
      patients with a large cup-to-disk ratio.
AB  - PURPOSE: To determine the relationship between quantitative nerve fiber layer
      measurements and visual field testing in patients with large cup-to-disk ratios.
      METHODS: Seventy-six patients with vertical cup-to-disk ratios by contour of at
      least 0.8 on stereoscopic photographs and 50 normal subjects were included. One
      eye was randomly selected for study. All patients underwent standard achromatic
      automated perimetry, short-wavelength automated perimetry, and retinal nerve
      fiber layer measurements with scanning laser polarimetry. Analysis of variance
      was used to evaluate differences between the subject groups. Significance of
      pairwise comparisons was determined using the Tukey-Kramer multiple comparison
      test. RESULTS: Statistically significant differences in nerve fiber layer
      measurements between patients with large cup-to-disk ratios and both abnormal
      standard achromatic automated perimetry and short-wavelength automated perimetry
      (n = 22) and patients with large cup-to-disk ratios and both normal standard
      achromatic automated perimetry and short-wavelength automated perimetry (n = 42)
      were found for superior nasal ratio, maximum modulation, ellipse modulation, and
      the linear discriminant function (Tukey-Kramer less than.05). There was no
      significant difference in patients with abnormal short-wavelength automated
      perimetry only (n = 9) as compared with patients with both normal standard
      achromatic automated perimetry and short-wavelength automated perimetry and
      patients with both abnormal standard achromatic automated perimetry and short
      wavelength automated perimetry. Statistically significant differences between the
      normal subjects and patients with large cup-to-disk ratios and both abnormal
      standard achromatic automated perimetry and short-wavelength automated perimetry
      were found for all retinal nerve fiber layer parameters, with the exception of
      symmetry, superior ratio, and inferior ratio. CONCLUSION: Our results show
      considerable overlap in nerve fiber layer measurements in eyes with large cup-to
      disk ratio and abnormal visual fields as compared with eyes with large cup-to
      disk ratios and normal visual fields. This may limit the clinical usefulness of
      scanning laser polarimetry for detection of early glaucoma in patients with large
      cup-to-disk ratios. Longitudinal studies are needed to determine if patients with
      large cup-to-disk ratios with normal standard achromatic automated perimetry and
      abnormal short-wavelength automated perimetry subsequently develop standard
      achromatic automated perimetry defects and if scanning laser polarimetry can
      concurrently detect progression of nerve fiber layer damage.

PMID- 11589871
TI  - Effects of cataract extraction with intraocular lens placement on scanning laser
      polarimetry of the peripapillary nerve fiber layer.
AB  - PURPOSE: To determine the effects of cataract extraction with intraocular lens
      placement on scanning laser polarimetry of the peripapillary nerve fiber layer.
      DESIGN: Cohort study. METHODS: Thirty-four eyes of 33 patients undergoing
      phacoemulsification cataract surgery with intraocular lens were imaged using the
      GDx Nerve Fiber Analyzer within 4 weeks before and at least 4 weeks after
      cataract surgery. Preoperative and postoperative mean images were compared. The
      effects of cataract severity and type, and intraocular lens material, were also
      examined. RESULTS: Comparison of preoperative and postoperative mean scanning
      laser polarimetry measurements revealed that eyes in which acrylic intraocular
      lenses (n = 11) were placed had a significant increase in scanning laser
      polarimetry for the total band circumference, and superior, inferior, and nasal
      quadrants (P < or =.041). Placement of silicone (n = 15) and
      polymethylmethacrylate (n = 8) intraocular lenses did not result in statistically
      significant changes in scanning laser polarimetry measurements. However, eight of
      34 eyes (23.5%) had changes of 15% or more postoperatively in the total
      circumference measurement, including eyes with acrylic, silicone, and
      polymethylmethacrylate intraocular lenses. CONCLUSIONS: Cataract extraction with
      intraocular lens was associated with a statistically significant change in mean
      scanning laser polarimetry values in eyes that received an acrylic intraocular
      lens. In individual patients, clinically important changes (15% or greater) in
      scanning laser polarimetry measurements were not uncommon irrespective of
      intraocular lens type. New baseline scanning laser polarimetry measurements may
      be warranted in eyes that undergo cataract extraction with intraocular lens.

PMID- 11589872
TI  - Retinal nerve fiber layer thickness remains unchanged following laser-assisted in
      situ keratomileusis.
AB  - PURPOSE: To evaluate the effect of laser-assisted in situ keratomileusis (LASIK)
      on retinal nerve fiber layer (RNFL) thickness measurements obtained with scanning
      laser polarimetry (SLP), optical coherence tomography (OCT), and scanning laser
      tomography (SLT). DESIGN: Interventional case series. METHODS: Twenty eyes (20
      patients) undergoing LASIK were enrolled in this prospective study. SLP, OCT, and
      SLT examinations were performed 1 week prior to and 1 week and 4 weeks after
      LASIK surgery. Intraocular pressure was normal at all preoperative and
      postoperative examinations. SLP, OCT, and SLT mean RNFL thickness values, and SLT
      RNFL cross sectional area, rim area, and rim volume before and after LASIK were
      compared by the Student paired t test. RESULTS: Mean patient age was 39.3 +/- 9.5
      (SD) years (range, 28 to 62 years). Mean preoperative spherical equivalent
      refractive error was -3.9 +/- 1.9 diopters (D) (range, -1.4 to -8.00 D) and mean
      spherical equivalent refractive surgical correction was 3.6 +/- 1.9 D (range,
      1.00 to 8.50 D). Mean RNFL thicknesses obtained by SLP were thinner 1 week and 4
      weeks after LASIK (P < 0.01, for all comparisons, paired t test), whereas mean
      OCT RNFL thickness and SLT RNFL thickness, RNFL cross-section area, rim area, and
      rim volume measurements were unchanged 1 week and 4 weeks after LASIK (P > or =
      0.05, for all comparisons, paired t test). CONCLUSIONS: LASIK does not affect
      RNFL thickness. Alterations in SLP RNFL thickness measurements are due to
      alterations in corneal architecture rather than an actual LASIK-induced RNFL
      injury.

PMID- 11589873
TI  - Corneal thickness measurements with contact and noncontact specular microscopic
      and ultrasonic pachymetry.
AB  - PURPOSE: To evaluate the central corneal thickness values in normal and
      postkeratoplasty corneas with the new Topcon SP-2000P noncontact specular
      microscopic, contact specular microscopic, and the "common standard" ultrasonic
      pachymetry. METHODS: Central corneal thickness was determined in 119 eyes of 81
      patients (73 normal eyes of 44 patients and 46 eyes after penetrating
      keratoplasty) first with a noncontact specular microscopic (Topcon SP-2000P;
      Topcon Corporation, Tokyo, Japan), then an ultrasonic (AL-1000; Tomey, Erlangen,
      Germany), and finally with a contact specular microscopic (EM-1000; Tomey,
      Erlangen, Germany) pachymetry two times each by the same investigator. RESULTS:
      Reliability of the central corneal measurements was equally high both in normal
      and in postkeratoplasty corneas with all of the instruments (Cronbach alpha =
      0.99). Noncontact specular microscopic corneal thickness determination correlated
      significantly both with ultrasonic (r =.86, P <.0001) and contact specular
      microscopic pachymetry (r =.62, P <.0001). The ultrasonic pachymetry correlated
      well with the Tomey pachymetry (r =.69, P <.0001). The Topcon normal mean central
      corneal thickness value (542 +/- 46 microm) was 28 +/- 4 microm lower (P <.0001)
      compared with the ultrasonic data (570 +/- 42 microm), which was 68 +/- 1 microm
      lower (P <.0001) compared with Tomey thickness (638 +/- 43 microm). CONCLUSIONS:
      Central corneal thickness measurements with noncontact specular microscopic,
      contact specular microscopic, and ultrasonic pachymetry demonstrate that each of
      the instruments is reliable but cannot be simply used interchangeably.

PMID- 11589874
TI  - Tyrosinemia type II: nine cases of ocular signs and symptoms.
AB  - PURPOSE: To report nine cases of tyrosinemia type II, with ocular signs and
      symptoms. METHODS: Participants included nine patients (18 eyes) who were
      followed for a mean follow-up period of 6.5 years (range, 2 to 8 years).
      Intervention included dietary restriction of tyrosine and phenylalanine, which
      led to resolution of ocular and cutaneous lesions, improved behavior in one
      patient, and may have prevented developmental delay in others. The main outcome
      measures were visual acuity and serum tyrosine levels to determine the response
      to dietary therapy. Intelligence testing and developmental screening were
      performed when appropriate. RESULTS: All patients presented with ocular signs and
      symptoms as the primary manifestation of disease and serve to illustrate the
      typical ocular findings of this syndrome. Three patients presented with cutaneous
      manifestations, and one patient had mild mental impairment at the time of
      diagnosis. CONCLUSIONS: Recalcitrant pseudodendritic keratitis may be the
      presenting sign in tyrosinemia type II. Awareness of the presenting signs and
      symptoms may accelerate the diagnosis and dietary intervention. Initiation of a
      tyrosine-restricted and phenylalanine-restricted diet in infancy is most
      effective in preventing cognitive impairment.

PMID- 11589876
TI  - Cataract and hearing loss in a population-based study: the Beaver Dam studies.
AB  - PURPOSE: Cataract and hearing loss are each common at older ages and together may
      influence the ability to function independently and affect the sense of well
      being. For these reasons, we sought to estimate the risk factors for comorbidity
      of age-related cataract and hearing loss. METHODS: A cross-sectional evaluation
      of a population-based cohort of older adults was conducted in Beaver Dam,
      Wisconsin, for presence of age-related cataract and hearing loss. The study
      evaluation included taking standardized medical histories, measuring blood
      pressures, and obtaining blood specimens. Standardized photographs, which were
      graded according to well-defined protocols to assess the presence of nuclear,
      cortical or posterior subcapsular cataract, were taken. Audiometric testing was
      performed according to well-defined study protocols. RESULTS: Any type of
      cataract in combination with hearing loss in either ear was frequent, occurring
      in 27.8% of the population overall and increasing consistently with age. Nuclear
      and posterior subcapsular cataract in combination with hearing loss occurred more
      often in men. Lifestyle factors that were associated with at least one cataract
      hearing loss end point in at least one sex were history of heavy drinking and
      smoking. CONCLUSIONS: In this community, older adults appear to be at high risk
      of cataract and hearing loss. Although risk is strongly associated with age, some
      elective exposures appear to influence risk. It is possible that modification of
      certain lifestyle habits may alter these risks.

PMID- 11589875
TI  - A decision analysis of anesthesia management for cataract surgery.
AB  - PURPOSE: To compare the trade-offs in cost and preference of various anesthesia
      management strategies for cataract surgery. METHODS: Six strategies, differing in
      sedation, local anesthetic, and monitoring approach, were chosen for comparison.
      For each strategy, potential complications, and conversions to different
      anesthesia approaches were modeled. A panel of physicians and anesthetists, well
      versed in the literature and practice of the anesthesia management of cataract
      surgery, assigned preference values to the strategies and potential outcomes (0
      to 1 scale). Probability estimates were obtained from a study of 19,557 cataract
      surgeries and from the panel. Cost estimates were derived from several sources.
      The model was analyzed to determine the strategies associated with the highest
      expected preference and lowest expected cost. RESULTS: The strategy associated
      with the highest net preference was intravenous sedation with block anesthesia
      and an anesthesiologist present throughout the case. The expected net preference
      for this strategy was 19% greater than the net preference for the next most
      preferred strategy, oral sedation with block anesthesia and an anesthesiologist
      on call (0.88 versus 0.74), but the expected anesthesia costs per case were much
      greater ($324 versus $42). Results were sensitive to plausible variation in the
      preference values assigned to the six initial management strategies and to the
      cost of topical versus block anesthesia. CONCLUSION: This analysis emphasizes
      that cost and preference are important considerations when choosing an anesthesia
      management strategy for cataract surgery. For some surgeries, substantial cost
      savings may be available for a small change in preference.

PMID- 11589877
TI  - Levels of basic fibroblast growth factor, glutamine synthetase, and interleukin-6
      in subretinal fluid from patients with retinal detachment.
AB  - PURPOSE: To investigate the presence of basic fibroblast growth factor, glutamine
      synthetase activity, and interleukin-6 in subretinal fluid from patients with
      retinal detachment. METHODS: In a prospective study we measured basic fibroblast
      growth factor, glutamine synthetase activity, interleukin-6, and total protein in
      subretinal fluid samples from 96 eyes from 94 consecutive patients with a retinal
      detachment corrected by a conventional scleral buckling operation in our clinical
      practice. As controls, vitreous fluid samples from eyes with a macular hole (n =
      6) or pucker (n = 11) were used. Laboratory data of the patient group were
      compared with the control group and correlated with various clinical data.
      RESULTS: Levels (median, range) of basic fibroblast growth factor, glutamine
      synthetase activity, interleukin-6, and total protein were significantly higher
      in patients than in controls (P <.0001). An increased level of glutamine
      synthetase and total protein correlated with a longer duration of the retinal
      detachment (r =.4, P =.002, and r =.34, P =.001, respectively). Interleukin-6 and
      basic fibroblast growth factor levels did not correlate with the duration of the
      detachment. After multivariate logistic regression analysis, no significant
      relation was found between any of the tested subretinal proteins and a low visual
      outcome or redetachment. CONCLUSIONS: We found increased levels of basic
      fibroblast growth factor and glutamine synthetase in subretinal fluid from
      patients with retinal detachment. Basic fibroblast growth factor and glutamine
      synthetase may play a role in the pathogenesis and recovery after retinal
      detachment. The questions of whether the increased levels of basic fibroblast
      growth factor and glutamine synthetase result from leakage of dying glia cells
      (including Muller cells) and neurons and if basic fibroblast growth factor is
      actively produced to protect the photoreceptor cells need further research.

PMID- 11589878
TI  - Expression of the inducible isoform of nitric oxide synthase in the retinas of
      human subjects with diabetes mellitus.
AB  - PURPOSE: Inducible nitric oxide synthase has been implicated in the pathogenesis
      of cerebral ischemic damage, in the angiogenic process and in diabetic vascular
      damage. This study was undertaken to determine whether inducible nitric oxide
      synthase is present in the retinas from human subjects with diabetes mellitus.
      METHODS: This was an experimental immunohistochemical prospective study. Ten
      postmortem eyes from five subjects with diabetes mellitus, 10 eyes from five
      subjects without diabetes and without known ocular disease, and two eyes from one
      subject with unilateral ocular ischemic syndrome secondary to severe carotid
      artery obstruction were examined. We used immunohistochemical techniques and
      antibodies directed against inducible nitric oxide synthase, glial fibrillary
      acidic protein, and vimentin. The main outcome measure was immunoreactivity for
      these antibodies. RESULTS: Immunoreactivity for inducible nitric oxide synthase
      was not observed in retinas from all subjects without diabetes and without ocular
      disease. Six retinas from three subjects with diabetes and nonproliferative
      retinopathy, and the retina from the eye with ocular ischemic syndrome showed
      immunoreactivity for inducible nitric oxide synthase in cells with elongated
      processes. Based on morphology and on glial fibrillary acidic protein and
      vimentin immunoreactivity, this inducible nitric oxide synthase immunoreactivity
      appeared to localize to retinal Muller glial cells. CONCLUSIONS: These
      observations suggest that Muller cells may be involved in the microvascular
      remodeling of the diseased retina and that high concentrations of nitric oxide
      produced by inducible nitric oxide synthase could contribute to neurotoxicity and
      angiogenesis that occur in diabetic retinopathy.

PMID- 11589879
TI  - Choriocapillaris photodynamic therapy using indocyanine green.
AB  - PURPOSE: To evaluate the potential of photodynamic therapy using indocyanine
      green for occlusion of choroidal neovascularization, the authors studied
      efficiency and collateral damage of photodynamic therapy-induced photothrombosis
      in the rabbit choriocapillary layer. METHODS: Fundus photography, fluorescein
      angiography, and light and transmission electron microscopy were used to study
      the efficiency of photodynamic therapy-induced photothrombosis using indocyanine
      green as the photosensitizer, and to assess the resultant collateral damage. The
      delivery system consisted of a modified infrared diode laser tuned to 810 nm,
      near the maximum absorption peak of indocyanine green. RESULTS: Choriocapillary
      occlusion was achieved at indocyanine green doses of 10 and 20 mg/kg and a
      radiant as low as 6.3 J/cm(2). When photodynamic therapy was performed with
      indocyanine green doses of 10 mg/kg, damage to the neural retina was minimal.
      Only inner photoreceptor segments showed degeneration, probably secondary to
      choroidal ischemia. Bruch membrane remained intact. Retinal pigment epithelium
      was invariably damaged, as seen with other photosensitizers. Temporary occlusion
      of large choroidal vessels occurred at both dye doses. CONCLUSIONS: In this
      experimental study, photodynamic therapy using indocyanine green and 810-nm light
      irradiation produced endothelium-bound intraluminal photothrombosis, with
      preservation of the retinal architecture and minimal loss of visual cells.
      Membrane targetability, hydrophilic and fluorescent properties, and activation at
      805 nm suggest indocyanine green as a potential photosensitizer for choroidal
      neovascularization. These combined considerations point toward further study of
      photodynamic therapy using indocyanine green for the treatment of choroidal
      vascular disease.

PMID- 11589880
TI  - Clinical Trials Digest on the Internet at AJO.COM: entering a new information
      age.

PMID- 11589881
TI  - The importance of differential sensitivity of the visual field to intraocular
      pressure.

PMID- 11589882
TI  - Ultrasound biomicroscopy before and after goniosynechialysis.
AB  - PURPOSE: To report the ultrasound biomicroscopic appearance of the anterior
      chamber angle before and after successful goniosynechialysis. METHODS:
      Interventional case report. Ultrasound biomicroscopy using a 50-MHz transducer
      was performed in the supine position preoperatively and postoperatively in a 76
      year-old woman with angle-closure glaucoma. RESULTS: Ultrasound biomicroscopy of
      the anterior chamber angle demonstrated restoration of an open anterior chamber
      angle after goniosynechialysis. CONCLUSION: High-resolution imaging of the
      anterior segment to evaluate preoperative and postoperative anatomy may be useful
      in eyes undergoing goniosynechialysis.

PMID- 11589883
TI  - Peritubular filtration as cause of severe hypotony after Ahmed valve implantation
      for glaucoma.
AB  - PURPOSE: To report peritubular filtration as the cause of severe hypotony after
      Ahmed valve implantation. METHODS: Interventional case report. In a 65-year-old
      man with primary open-angle glaucoma, ultrasound biomicroscopy was used to image
      the peritubular region of his right eye that had severe hypotony during the early
      postoperative period after an Ahmed valve implantation. RESULTS: The ultrasound
      biomicroscopy examination showed peritubular filtration. Additional surgery
      consisting of tube extraction, closure of the previous insertion opening,
      reformation of the anterior chamber with viscoelastic, and reintroduction of the
      tube through a new paracentesis was performed to solve this complication. Twenty
      four hours postoperatively, the intraocular pressure increased to 10 mm Hg.
      During the 6-month follow-up, the mean intraocular pressure was 16.36 mm Hg
      (standard deviation, 1.45). CONCLUSION: The possibility of peritubular filtration
      should be considered in eyes with severe hypotony after restrictive valve
      implantation.

PMID- 11589884
TI  - A novel (Pro79Thr) mutation in the FKHL7 gene in a Japanese family with Axenfeld
      Rieger syndrome.
AB  - PURPOSE: To report the ocular and genetic findings of a Japanese family with
      Axenfeld-Rieger syndrome associated with a novel Pro79Thr mutation in the FKHL7
      gene. METHODS: Observational case series. Genomic DNA of patients from a family
      with Axenfeld-Rieger syndrome was extracted from leukocytes, and exons of the
      FKHL7 gene were amplified by polymerase chain reaction for direct sequencing.
      RESULTS: Molecular genetic analysis disclosed that one Japanese family with
      Axenfeld-Rieger syndrome had a heterozygous C to A transversion in the first
      nucleotide at codon 79, designated Pro79Thr mutation in the FKHL7 gene.
      CONCLUSION: Considering this novel Pro79Thr mutation together with previously
      reported findings, it is indicated that the clinical features of Axenfeld-Rieger
      syndrome may depend on the portion of the FKHL7 gene affected by the mutation,
      although more case reports are needed to clarify genotype-phenotype correlations
      of the FKHL7 gene.

PMID- 11589885
TI  - Cat-scratch disease neuroretinitis diagnosed by a polymerase chain reaction
      approach.
AB  - PURPOSE: To assess the value of polymerase chain reaction in the diagnosis of cat
      scratch disease neuroretinitis without conclusive serology. METHODS:
      Interventional case report. A 13-year-old girl developed a right neuroretinitis 2
      months after a cat scratch. Despite the lack of accompanying features, an
      infection by Bartonella henselae was suspected and a systemic check-up was
      performed. RESULTS: Serologic results excluded other proposed origins but were
      insufficient in making the diagnosis because of low B. henselae specific IgG
      level in serum. A polymerase chain reaction analysis for B. henselae DNA in a
      small axillary lymphadenopathy aspirate enabled us to achieve a definitive
      diagnosis of cat-scratch disease. CONCLUSION: Polymerase chain reaction is a
      valuable method of diagnosing cat-scratch disease when serology is considered
      negative or borderline.

PMID- 11589886
TI  - Management of conjunctival and corneal melanoma with surgical excision, amniotic
      membrane allograft, and topical chemotherapy.
AB  - PURPOSE: To illustrate a novel method of management for extensive conjunctival
      and corneal melanoma. METHODS: Interventional case report. A 40-year-old
      Caucasian woman presented with a large, diffuse conjunctival melanoma involving 6
      clock hours of the limbus. The remaining bulbar conjunctiva and the entire
      corneal epithelium were affected by diffuse, flat melanosis. RESULTS: The
      conjunctival melanoma was completely resected microsurgically in one piece
      without disrupting the tumor. The conjunctival melanosis was treated with double
      freeze-thaw cryotherapy. The extensive conjunctival defect, involving one-half of
      the bulbar conjunctiva, was reconstructed with an amniotic membrane allograft.
      The corneal melanosis was subsequently treated with topical mitomycin C eyedrops.
      At 8 months follow-up, the conjunctiva and the cornea were completely healed with
      resolution of all pigment and 20/20 visual acuity. CONCLUSION: Preliminary
      evidence suggests that combined therapeutic approaches, consisting of extensive
      tumor removal, cryotherapy, amniotic membrane allograft, and topical mitomyin C,
      can be effective in the management of diffuse conjunctival and corneal melanoma
      arising from primary acquired melanosis.

PMID- 11589888
TI  - Evaluation of the peripheral visual field after foveal translocation.
AB  - PURPOSE: To evaluate the peripheral visual field after foveal translocation with
      scleral imbrication or 360-degree retinotomy. METHODS: Retrospective, single
      center, nonrandomized study. We calculated the rate of preservation of the
      peripheral visual field using Goldmann perimetry by dividing the width of the
      postoperative V-4 isopter by the preoperative width and expressing the result as
      a percentage. RESULTS: In nine eyes that underwent scleral imbrication, the rate
      of preservation was 100.0% superiorly, 102.6% superotemporally, 99.9% temporally,
      97.9% inferotemporally, 96.9% inferiorly, 82.3% inferonasally, 93.7% nasally, and
      87.3% superonasally. In 33 eyes that underwent 360-degree retinotomy, it was
      89.1%, 87.0%, 81.9%, 78.1%, 86.6%, 90.0%, 89.9%, and 86.8%, respectively.
      CONCLUSION: After foveal translocation with scleral imbrication, the peripheral
      visual field was preserved except for slight narrowing nasally; 360-degree
      retinotomy resulted in preservation of the visual field, except for slight
      narrowing in all meridians.

PMID- 11589887
TI  - Melanoma-associated retinopathy and recurrent exudative retinal detachments in a
      patient with choroidal melanoma.
AB  - PURPOSE: To report a patient who presented with photopsias, night blindness,
      exudative retinal detachments, and melanoma-associated retinopathy in her right
      eye 23 years after the left eye was enucleated for a choroidal melanoma. METHODS:
      Assessment of fundus findings, fluorescein angiograms, and electroretinograms.
      RESULTS: The patient had recurrent exudative detachments of the macula in her
      right eye and electroretinogram responses consistent with the diagnosis of
      melanoma-associated retinopathy. The abdominal computed tomography (CT) scan was
      negative, but 13 months later, CT scanning revealed many masses in her liver.
      Fine-needle biopsy confirmed the diagnosis of metastatic melanoma. CONCLUSION: To
      our knowledge, this is the first report of melanoma-associated retinopathy in a
      patient with a previous choroidal melanoma.

PMID- 11589889
TI  - Retinal vasculitis associated with chickenpox.
AB  - PURPOSE: To report retinal vasculitis in a young, immunocompetent Asian female
      adult with chickenpox. METHODS: Interventional case report. A 32-year-old woman
      had chickenpox 2 weeks before blurred vision in the left eye. The visual acuity
      was 20/20 for the right eye and 30/50 for the left eye. The left eye presented
      keratic precipitates, moderate (2+) cells in the anterior chamber and numerous
      cells (3+) in the vitreous. The disk was normal. Perivenous exudation was noted
      mainly in the inferior retina. The sheathed retinal vessels showed late staining
      but no remarkable leakage on fluorescein angiography. The right eye was normal.
      RESULTS: After treatment with acyclovir for 10 days, the visual acuity in the
      left eye improved to 20/20, and the vasculitis resolved. CONCLUSION: Retinal
      vasculitis may present as a complication of primary varicella infection in an
      immunocompetent adult.

PMID- 11589890
TI  - Laser photocoagulation for choroidal neovascularization associated with
      sympathetic ophthalmia.
AB  - PURPOSE: To present a case of choroidal neovascularization associated with
      sympathetic ophthalmia successfully treated with photocoagulation. DESIGN:
      Interventional case report. METHODS: A 41-year-old man with a history of
      penetrating injury right eye, as well as sympathetic ophthalmia left eye,
      developed a classic choroidal neovascular membrane that threatened the center of
      the fovea. RESULTS: The patient was treated with argon laser photocoagulation. He
      has maintained stable visual acuity without evidence of recurrence of the
      membrane with 4 years' follow-up. CONCLUSION: Thermal laser should be considered
      as a treatment option in cases of choroidal neovascularization associated with
      sympathetic ophthalmia.

PMID- 11589891
TI  - Inhibitory effect of losartan on laser-induced choroidal neovascularization in
      rats.
AB  - PURPOSE: To investigate the inhibitory effects of losartan, an angiotensin
      receptor antagonist, on angiogenesis in a rat model of laser-induced choroidal
      neovascularization. METHODS: Experimental study. Fifteen Brown-Norway male rats
      received losartan (approximately 5 mg/kg/d) in drinking water, and 15 Brown
      Norway male rats received unsupplemented drinking water 1 week before
      photocoagulation, and it was continued to the end of the study. Two weeks after
      intense laser photocoagulation, choroidal neovascularization was evaluated by
      fluorescein angiography and histopathologic evaluation. RESULTS: The incidence of
      choroidal neovascularization formation was 99.5 +/-.2% (mean +/- standard
      deviation) in controls and 72.5 +/- 8.8% in losartan-treated rats (P <.01).
      Quantitative morphometric assessment revealed mean choroidal neovascularization
      lesion thickness of 54 and 44.8 microm, respectively, in controls and losartan
      treated rats (P <.01). CONCLUSION: Losartan seems to inhibit development of laser
      induced choroidal neovascularization. Angiotensin receptor antagonists may be
      useful as prophylaxis against choroidal neovascularization associated with age
      related macular degeneration.

PMID- 11589892
TI  - Unilateral papilledema caused by a fronto-temporo-parietal arachnoid cyst.
AB  - PURPOSE: To report a case of unilateral papilledema caused by an arachnoid cyst.
      METHODS: Interventional case report. RESULTS: A 36-year-old woman presented with
      unilateral papilledema in the left eye. Magnetic resonance imaging (MRI) of the
      brain demonstrated a large fronto-temporo-parietal arachnoid cyst in the left
      hemisphere. The papilledema resolved after placement of a cysto-peritoneal shunt
      that drained the cerebrospinal fluid directly from the arachnoid cyst into the
      peritoneum. CONCLUSION: Papilledema caused by increased intracranial pressure is
      usually bilateral; unilateral papilledema is possible under special anatomical
      circumstances.

PMID- 11589893
TI  - Leber hereditary optic neuropathy, progressive visual loss, and multiple
      sclerosis-like symptoms.
AB  - PURPOSE: To report a case of Leber hereditary optic neuropathy with multiple
      sclerosis-like symptoms. METHODS: Observational case report. A 34-year-old man
      was found to have Leber hereditary optic neuropathy and a mutation at position
      11778 of the mitochondrial genome. The progression of vision loss and onset of
      weakness in the right leg warranted neuroimaging. RESULTS: Magnetic resonance
      imaging documented multiple lesions in the brain and spinal cord. CONCLUSION:
      Although rarely reported, progression of optic neuropathy over months has been
      previously documented in Leber hereditary optic neuropathy. The emergence of
      multiple sclerosis-like symptoms and signs in our patient may be part of the
      spectrum of Leber hereditary optic neuropathy or a coincidental occurrence.

PMID- 11589894
TI  - Isolated bilateral trochlear nerve palsy as the first clinical sign of a
      metastatic [correction of metastasic] bronchial carcinoma.
AB  - PURPOSE: To report a case with isolated, nontraumatic bilateral fourth nerve
      palsy as the first clinical sign of a metastatic lung carcinoma. METHODS: Case
      report. A 56-year-old man presented with isolated, nontraumatic bilateral fourth
      nerve palsy. Magnetic resonance imaging (MRI) of the brain and orbits and,
      subsequently, chest x-ray and a computer tomographic (CT)-scan of the thorax, the
      abdomen, and the pelvis were performed. RESULTS: Magnetic resonance imaging
      confirmed the presence of a midline brain stem lesion in the region of
      decussation of the trochlear nerves. Computed tomographic scan of the chest
      revealed that the lesion was caused by a metastatic lung carcinoma. CONCLUSION:
      The findings of isolated bilateral fourth nerve palsy in the absence of trauma
      should alert the clinician to the possibility of a posterior fossa lesion in the
      region of the trochlear nerves. Besides urgent scanning of the dorsal midbrain,
      investigations should be directed to search for the primary tumor.

PMID- 11589895
TI  - Myoepithelioma metastatic to the orbit.
AB  - PURPOSE: To report a case of myoepithelioma metastatic to the orbit in an 11-year
      old boy. METHODS: Interventional case report. An 11-year-old white male with a
      history of resection of a left thigh mass 10 months previously presented with a
      painless, rapid swelling of the left upper eyelid. Computed tomography scan and
      incisional biopsy of the orbital mass were performed. RESULTS:
      Immunohistochemical stains of the tumor in the left orbit and the previously
      resected mass were consistent with myoepithelioma. As a result of widespread
      metastases, the patient died 4 months after initial presentation to the eye
      clinic. CONCLUSION: Myoepithelioma should be included in the differential
      diagnosis of neoplasms that can metastasize to the orbit in the pediatric age
      group.

PMID- 11589896
TI  - Ocular manifestations of Seckel syndrome.
AB  - PURPOSE: To report ophthalmic findings in three siblings with Seckel syndrome.
      METHODS: Observational case report. Three siblings with Seckel syndrome were
      examined. RESULTS: Severe bilateral pigmentary retinopathy with severe myopia and
      astigmatism was found in all three patients. Electroretinography was performed on
      the eldest sibling and showed no detectable rod or cone responses. CONCLUSION:
      Severe, early onset, bilateral retinal degeneration with severe myopia and
      astigmatism may be associated with Seckel syndrome.

PMID- 11589910
TI  - Alzheimer's Disease versus other Degenerative Dementias: from Biology to
      Treatment. Proceedings of a meeting. Perugia, Italy, June 17, 2000.

PMID- 11589911
TI  - Pathophysiological aspects of frontotemporal dementia--emphasis on cytoskeleton
      proteins and autoimmunity.
AB  - The aim of this study was to investigate two putative pathophysiological aspects
      of the common neurodegenerative disorder frontotemporal dementia (FTD). To this
      end, cerebrospinal fluid (CSF) levels of tau (total tau) and the light subtype of
      the neurofilament proteins (NFL) were studied in patients with FTD (n=16) and in
      age-matched controls (n=16). In addition, serum was analysed for IgG and IgM
      antibodies to the most common gangliosides and sulfatide in FTD patients (n=13)
      and in age-matched controls (n=20). The CSF-NFL levels were increased in FTD
      (1606+/-1151 pg/ml, mean+/-S.D.; P<0.001) compared with controls (308+/-203
      pg/ml), whereas the CSF-tau levels were normal. In serum, autoantibody IgG-GA1
      was significantly increased in FTD (P<0.05) compared with controls. No
      correlations were found between the effect parameters and demographic variables
      in any group. The results of this study suggest that cytoskeleton proteins other
      than tau are also involved in the pathophysiology of FTD and that autoimmunity
      may be part of the pathophysiological processes in FTD, as it is believed to be
      in Alzheimer's disease.

PMID- 11589912
TI  - Cerebrospinal fluid cytoskeleton proteins in patients with subcortical white
      matter dementia.
AB  - The cerebrospinal fluid (CSF) levels of two cytoskeleton proteins, tau and the
      light subunit of neurofilament protein (NFL), both considered to reflect cerebral
      white-matter components, were investigated in a group of patients with a subtype
      of vascular dementia called 'subcortical white-matter dementia' (SWD). The group
      consisted of 25 demented patients with frontosubcortical brain syndromes, white
      matter changes on computed tomography or magnetic resonance imaging and vascular
      disease or pronounced vascular risk factors. CSF-NFL was increased, whereas CSF
      tau was normal, suggesting a differential involvement of the cytoskeleton in this
      patient group. The albumin ratio and the apolipoproteinE4 (ApoE4) allele status
      were also investigated. The albumin ratio was increased, indicating damage to the
      vessel walls with breakdown of the blood-brain barrier. No relationship was found
      between ApoE4 alleles and CSF levels of tau or NFL in this patient group. Besides
      presenting original data, the disease status of SWD is also discussed.

PMID- 11589913
TI  - Genetic risk factors in familial Alzheimer's disease.
AB  - In the last 10 years significant progress has been made to describe and identify
      the underlying biological mechanisms that cause the different manifestation of
      Alzheimer's disease. Since the first report of a possible locus on chromosome 21
      in a small group of families with early onset familial Alzheimer's disease (FAD),
      considerable progress has been made. Results from linkage analysis and gene
      sequencing has provided evidence that a minority of early onset FAD families
      develops the disease as a result of mutations in the gene coding for the Abeta
      amyloid precursor protein, and that mutations in presenilin 1 and 2 genes account
      for a larger subgroup of early onset families. Several other early onset FAD
      families are clearly not linked to any of these loci, suggesting that other
      genetic risk factors may exist. Recent genome-wide scanning studies have revealed
      the existence of a new locus on chromosome 12, which, together with inheritance
      of the epsilon4 allele of apolipoprotein E gene, on chromosome 19, represent the
      most important genetic factors associated with an increased risk of developing
      the disease in late onset FAD families.

PMID- 11589914
TI  - Acetylcholinesterase in Alzheimer's disease.
AB  - Since the discovery of the cholinergic deficit in Alzheimer disease (AD),
      acetylcholinesterase (AChE) has been widely investigated in tissues involved in
      the disease. These studies showed modifications in AChE activity and changes in
      its polymorphism in brain as well as in cerebro-spinal fluid (CSF) and blood. The
      co-localization of the enzyme in the senile plaque provided evidence of its
      anomalous features. It has been also shown that AChE forms a stable complex with
      senile plaque components through its peripheral anionic site. Moreover, the
      neurotoxicity of amyloid components is increased by the presence of AChE. The
      occurrence of an altered glycosylation of some AChE forms in AD is closely
      related to the presence of amyloid formations. Literature on expression,
      relationships and modifications in the molecular polymorphism of AChE, in brain,
      CSF and blood in AD is reviewed.

PMID- 11589915
TI  - Activation of complement and contact system in Alzheimer's disease.
AB  - beta-Amyloid protein (betaA) has been implicated in the pathogenesis of
      Alzheimer's disease (AD) because of its neurotoxicity and ability to trigger a
      local inflammatory response. Although assembly of betaA in particular aggregates
      seems to be crucial event in AD pathogenesis, soluble, non-fibrillar betaA may
      also be involved. Non-fibrillar betaA1-42, and truncated peptide 1-28, induced
      dose-dependent activation of C4 sparing C3. The mechanism of C4 activation was
      not dependent on C1q, because non-fibrillar betaA can still activate C4 in plasma
      genetically deficient in C1q. A C1q independent mechanism of complement classical
      pathway activation could be via the activation of contact/kinin system. The
      possible involvement of contact system in AD is suggested by the finding that
      this system is massively activated in CSF of AD patients. The mechanism of
      activation of contact system could be the result of an anionic interaction of
      residues within the region 1-11 of betaA1-42 with factor XII, and of kallikrein
      generation. Concomitant incubation of a small cationic peptide (lysine4) with
      betaA abrogated its ability to trigger the cleavage of high molecular weight
      kininogen. In vivo, prevention of contact system activation beside the reduction
      of kallikrein generation, can also decrease the activation of complement system
      and the release of interleukin-6, both factors being considered to play an
      important role in the inflammatory reactions in AD brain.

PMID- 11589916
TI  - Inflammatory markers in Alzheimer's disease and multi-infarct dementia.
AB  - Inflammation has been involved in the pathogenesis of dementia. The study
      evaluates the presence and the source of pro- and anti- inflammatory cytokines in
      the blood of patients with Alzheimer's disease (AD), multi-infarct dementia (MID)
      or in non-demented elderly people (controls). Tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-1beta, IL-6, IL-10, IL-1 receptor antagonist (IL-1Ra) and
      soluble TNF receptor I (sTNF-RI) plasma concentrations and release from blood
      cells stimulated with lipopolysaccharide (LPS, 1 microg/ml) were determined. The
      results show that TNF-alpha released from blood cells is significantly decreased
      (27%) in all demented patients compared to controls. Circulating TNF-alpha is
      increased (400%) only in MID patients. In these patients plasma levels of sTNF-RI
      are increased (53%) and IL-10 from stimulated blood cells decreased (47%)
      compared to non-demented subjects. The results show that: (1) peripheral
      production of TNF-alpha is blunted in demented (both AD and MID) patients
      compared to non-demented age-matched subjects; (2) AD patients have a selective
      disregulation of the peripheral TNF-alpha system; (3) different cytokines are up-
      or down- regulated in MID patients showing that in this condition the pro- and
      anti-inflammatory peripheral cytokine system is more widely affected.

PMID- 11589917
TI  - Platelet amyloid precursor protein forms in AD: a peripheral diagnostic tool and
      a pharmacological target.
AB  - Alzheimer Disease (AD) is characterized by the progressive deposition of beta
      amyloid in the parenchyma and cerebral microvasculature. The beta-amyloid peptide
      derives from the metabolism of a larger precursor, Amyloid Precursor Protein
      (APP). This protein is present in central nervous system, but it is also
      expressed in peripheral tissues such as circulating cells. An alteration of the
      APP forms pattern in platelets has been recently reported in AD patients when
      compared to platelets both of control subjects or non AD patients (NADD). The
      accuracy of the assay to identify AD is high and decreased levels are found
      throughout the course of AD with a significant association with severity of
      symptoms. Moreover, a recent study has demonstrated that AD patients on donepezil
      (5 mg daily) for 4 weeks displayed two-fold increase in their APPr baseline
      levels up to normal range. Thus, platelet APP ratio (APPr) holds the potential to
      be a clinical marker, which might be of helpful and adjunctive value in the
      diagnosis of AD and in tracking the course of illness, also in the early stages
      when pharmacological treatment has the greatest potential of being effective.

PMID- 11589919
TI  - Plasma total homocysteine levels and the C677T mutation in the
      methylenetetrahydrofolate reductase (MTHFR) gene: a study in an Italian
      population with dementia.
AB  - Hyperhomocysteinemia is a known risk factor for vascular disease and commonly
      occurs in the elderly. Several studies have shown an association between elevated
      plasma homocysteine levels and cognitive impairment, indicating that it may play
      a role in the pathophysiology of dementia. We studied plasma homocysteine,
      folate, vitamin B12 levels and the MTHFR C677T genotype in an Italian population
      of patients with dementia. We confirmed that elevated plasma tHcy (>14
      micromol/l) is common in elderly subjects with dementia. Although we found a high
      prevalence of the MTHFR TT genotype (21.2%) the allele frequency is not over
      represented relative to the control population. We also observed a high incidence
      of folate deficiency (38%) in subjects with dementia. Elevated homocysteine was
      associated with low plasma folate (<5.7 nmol/l) and the MTHFR TT genotype.
      Moderate to severe hyperhomocysteinemia (>26.1 nmol/l) was associated with a
      significantly lower MMSE score. Hyperhomocysteinemia may be neurotoxic by several
      different mechanisms affecting cognitive function. Further studies are needed to
      fully explore the potential of B vitamin supplementation to lower plasma
      homocysteine and improve cognitive function.

PMID- 11589918
TI  - Cerebrospinal fluid tau and beta-amyloid(1-42) in dementia disorders.
AB  - The reliability of cerebrospinal fluid (CSF)-tau and CSF-beta-amyloid assays for
      diagnosis of Alzheimer's disease and other dementing disorders such as
      frontotemporal dementia (FTD), dementia with Lewy bodies (DLB) and Creutzfeldt
      Jakob disease (CJD) is reviewed. CSF assessment of the two proteins is useful in
      early diagnosis of AD and to differentiate it from FTD and DLB. Extremely high
      CSF-tau levels can discriminate CJD from AD.

PMID- 11589920
TI  - Treatment of cognitive dysfunction associated with Alzheimer's disease with
      cholinergic precursors. Ineffective treatments or inappropriate approaches?
AB  - The observations of the loss of cholinergic function in neocortex and hippocampus
      in Alzheimer's disease (AD) developed the hypothesis that replacement of
      cholinergic function may be of therapeutic benefit to AD patients. The different
      approaches proposed or tested included intervention with acetylcholine (ACh)
      precursors, stimulation of ACh release, use of muscarinic or nicotinic receptor
      agonists and acetylcholinesterase (AChE) or cholinesterase (ChE) inhibition.
      Inhibition of endogenous ACh degradation through ChE inhibitors and precursor
      loading were treatments more largely investigated in clinical trials. Of the
      numerous compounds in development for the treatment of AD, AChE and ChE
      inhibitors are the most clinically advanced, although clinical trials conducted
      to date did not always confirm a significant benefit of these drugs on all
      symptom domains of AD. The first attempts in the treatment of AD with cholinergic
      precursors did not confirm a clinical utility of this class of compounds in well
      controlled clinical trials. However, cholinergic precursors most largely used
      such as choline and phosphatidylcholine (lecithin) were probably not suitable for
      enhancing brain levels of ACh. Other phospholipids involved in choline
      biosynthetic pathways such as CDP-choline, choline alphoscerate and
      phosphatidylserine clearly enhanced ACh availability or release and provided a
      modest improvement of cognitive dysfunction in AD, these effects being more
      pronounced with choline alphoscerate. Although some positive results cannot be
      generalized due to the small numbers of patients studied, they probably would
      justify reconsideration of the most promising molecules in larger carefully
      controlled trials.

PMID- 11589921
TI  - Choline alphoscerate in cognitive decline and in acute cerebrovascular disease:
      an analysis of published clinical data.
AB  - This paper has reviewed the documentation on the clinical efficacy of choline
      alphoscerate, a cholinergic precursor, considered as a centrally acting
      parasympathomimetic drug in dementia disorders and in acute cerebrovascular
      disease. Thirteen published clinical trials, examining in total 4054 patients,
      have evaluated the use of choline alphoscerate in various forms of dementia
      disorders of degenerative, vascular or combined origin, such as senile dementia
      of the Alzheimer's type (SDAT) or vascular dementia (VaD) and in acute
      cerebrovascular diseases, such as transitory ischemic attack (TIA) and stroke.
      Analysis has assessed the design of each study, in particular with respect to
      experimental design, number of cases, duration of treatment and tests used to
      evaluate drug clinical efficacy. Most of the ten studies performed in dementia
      disorders were controlled trials versus a reference drug or placebo. Overall,
      1570 patients were assessed in these studies, 854 of which in controlled trials.
      As detected by validated and appropriate tests, such as Mini Mental State
      Evaluation (MMSE) in SDAT and Sandoz Clinical Assessment Geriatric (SCAG) in VaD,
      administration of choline alphoscerate significantly improved patient clinical
      condition. Clinical results obtained with choline alphoscerate were superior or
      equivalent to those observed in control groups under active treatment and
      superior to the results observed in placebo groups. Analysis stresses the clear
      internal consistency of clinical data gathered by different experimental
      situations on the drug effect, especially with regard to the cognitive symptoms
      (memory, attention) characterising the clinical picture of adult-onset dementia
      disorders. The therapeutic usefulness of choline alphoscerate in relieving
      cognitive symptoms of chronic cerebral deterioration differentiates this drug
      from cholinergic precursors used in the past, such as choline and lecithin. Three
      uncontrolled trials were performed with choline alphoscerate in acute
      cerebrovascular stroke and TIA, totalling 2484 patients. The results of these
      trials suggest that this drug might favour functional recovery of patients with
      cerebral stroke and should be confirmed in future investigations aimed at
      establish the efficacy of the drug in achieving functional recovery of patients
      with acute cerebrovascular disease.

PMID- 11589922
TI  - Cerebrospinal fluid acetylcholinesterase activity after long-term treatment with
      donepezil and rivastigmina.
AB  - At present acetylcholinesterase (AChE) inhibitors (AChEIs) represent the only
      reliable therapeutic resource for symptomatic treatment of Alzheimer Disease
      (AD). This study was designed to assess the effects of 6-12 month treatment with
      AChEIs donepezil and rivastigmine on cerebrospinal fluid (CSF) AChE and
      butyrylcholinesterase (BuChE) activity in AD patients. The pattern of AChE
      isoforms (G4, G1, G2) before and after treatment was investigated as well. In AD
      patients treated with donepezil a significant increase of CFS AChE activity was
      observed, whereas treatment with rivastigmine induced a significant decrease of
      AChE activity. Both drugs did not change BuChE activity and tended to restore the
      physiological pattern of AChE isoform. The possible significance of the influence
      of AChEIs on CSF AChE activity and isoforms is discussed.

PMID- 11589923
TI  - Pharmacological treatment of non-cognitive disturbances in dementia disorders.
AB  - Behavioral and psychological symptoms of dementia (BPSD) occur in 50-90% of
      patients with Alzheimer's disease (AD). They cause premature
      institutionalization, increased costs of care and significant loss of quality-of
      life for the patient and his/her family and caregivers. Non-pharmacological
      interventions are first-line in dealing with milder BPSD, while for moderate to
      severe BPSD, medication is clearly indicated in conjunction with non
      pharmacological interventions. An imbalance of different neurotransmitters
      (acetylcholine, dopamine, noradrenaline, serotonin) has been proposed as the
      neurochemical correlate of BPSD. An involvement of some specific brain regions
      responsible for emotional activities (parahippocampal gyrus, dorsal raphe, locus
      coeruleus) and cortical hypometabolism have been suggested to contribute to BPSD.
      Atypical or novel antipsychotic drugs represent the reference drugs for treating
      BPSD. Among these, risperidone is considered as a drug of choice. Also, selective
      serotonin reuptake inhibitors (SSRIs) are useful in the treatment of BPSD.

PMID- 11589924
TI  - Age-related changes of dopamine receptors in the rat hippocampus: a light
      microscope autoradiography study.
AB  - Hippocampus is a brain region involved in learning and memory and is particularly
      sensitive to ageing. It is supplied with a dopaminergic innervation arising from
      the midbrain, which is part of the mesolimbic dopaminergic pathway. Dysfunction
      of the dopaminergic mesolimbic system is probably involved in the pathophysiology
      of psychosis and behavioural disturbances occurring in the elderly. The present
      study was designed to assess the density and localisation of dopamine D1- and D2
      like receptor subtypes in the hippocampus of male Sprague-Dawley rats aged 3
      months (young), 12 months (adult) and 24 months (old). Dopamine D1-like
      receptors, labelled by [3H]-SCH 23390, in young rats displayed a dentate gyrus
      CA1 subfield gradient. The expression was increased in the cell body of dentate
      gyrus, CA4 and CA3 subfield of old rats compared to younger cohorts, as well as
      in the neuropil of dentate gyrus. A decreased density of dopamine D1-like
      receptors was found in the stratum oriens of CA1 and CA3 subfields. Dopamine D2
      like receptors, labelled using [3H]-spiperone as radioligand, were expressed
      rather homogeneously throughout different subfields of the hippocampus. In old
      rats, the density of dopamine D2-like receptors was decreased in the dentate
      gyrus, unchanged in the CA4 and CA1 subfields and increased in the CA3 subfield.
      The above results indicate the occurrence of inhomogeneous changes in the density
      of dopamine D1- and D2-like receptors in specific portions of hippocampus of old
      rats. These findings support the hypothesis of an involvement of dopaminergic
      system in behavioural abnormalities or psychosis occurring in ageing.

PMID- 11589925
TI  - Hypertensive brain damage: comparative evaluation of protective effect of
      treatment with dihydropyridine derivatives in spontaneously hypertensive rats.
AB  - Hypertension is the main risk factor for cerebrovascular disease including
      vascular dementia and control of blood pressure might protect from lesions
      causing cognitive impairment. The influence of anti-hypertensive treatment on
      hypertensive brain damage was assessed in spontaneously hypertensive rats (SHR).
      SHR and age-matched normotensive Wistar Kyoto (WKY) rats were treated from the 14
      26th week of age with the dihydropyridine-type Ca2+ channel blockers
      lercanidipine, manidipine and nimodipine and as a reference with the non
      dihydropyridine-type vasodilator hydralazine. Volume of brain areas, number of
      nerve cells and glial fibrillary-acidic protein (GFAP)-immunoreactive astrocytes
      and neurofilament 200 kDa immunoreactivity were investigated in frontal and
      occipital cortex and in hippocampus. In control SHR, systolic blood pressure
      (SBP) was significantly higher in comparison with WKY rats. Compounds tested
      decreased to a similar extent SBP values in SHR, with the exception of nimodipine
      that caused a smaller reduction of SBP compared with other compounds. Decreased
      volume and number of nerve cells and loss of neurofilament protein
      immunoreactivity were observed in SHR. GFAP-immunoreactive astrocytes increased
      in number (hyperplasia) and in size (hypertrophy) in the frontal and occipital
      cortex of control SHR, and only in number in the hippocampus. Anti-hypertensive
      treatment countered in part microanatomical changes occurring in SHR. Drugs
      investigated with the exception of nimodipine exerted an equi-hypotensive effect.
      In spite of this the best protection was exerted by lercanidipine and, to a
      lesser extent, by nimodipine. Compared with nimodipine, lercanidipine induced a
      more effective decrease of SBP. This may represent an advantage in the treatment
      of hypertension with risk of brain damage.

PMID- 11589926
TI  - Nor any drop to drink.

PMID- 11589927
TI  - Blood-pressure lowering for the secondary prevention of stroke.

PMID- 11589928
TI  - Trimethoprim-sulfamethoxazole prophylaxis in sub-Saharan Africa.

PMID- 11589929
TI  - Is LBP-1c/CP2/LSF a disease-modifying gene for Alzheimer's disease?

PMID- 11589930
TI  - Prenatal detection of chromosome disorders by QF-PCR.

PMID- 11589931
TI  - Hallucinations in Parkinson's disease.

PMID- 11589932
TI  - Randomised trial of a perindopril-based blood-pressure-lowering regimen among
      6,105 individuals with previous stroke or transient ischaemic attack.
AB  - BACKGROUND: Blood pressure is a determinant of the risk of stroke among both
      hypertensive and non-hypertensive individuals with cerebrovascular disease.
      However, there is uncertainty about the efficacy and safety of blood-pressure
      lowering treatments for many such patients. The perindopril protection against
      recurrent stroke study (PROGRESS) was designed to determine the effects of a
      blood-pressure-lowering regimen in hypertensive and non-hypertensive patients
      with a history of stroke or transient ischaemic attack. METHODS: 6105 individuals
      from 172 centres in Asia, Australasia, and Europe were randomly assigned active
      treatment (n=3051) or placebo (n=3054). Active treatment comprised a flexible
      regimen based on the angiotensin- converting-enzyme inhibitor perindopril (4 mg
      daily), with the addition of the diuretic indapamide at the discretion of
      treating physicians. The primary outcome was total stroke (fatal or non-fatal).
      Analysis was by intention to treat. FINDINGS: Over 4 years of follow up, active
      treatment reduced blood pressure by 9/4 mm Hg. 307 (10%) individuals assigned
      active treatment suffered a stroke, compared with 420 (14%) assigned placebo
      (relative risk reduction 28% [95% CI 17-38], p<0.0001). Active treatment also
      reduced the risk of total major vascular events (26% [16-34]). There were similar
      reductions in the risk of stroke in hypertensive and non-hypertensive subgroups
      (all p<0.01). Combination therapy with perindopril plus indapamide reduced blood
      pressure by 12/5 mm Hg and stroke risk by 43% (30-54). Single-drug therapy
      reduced blood pressure by 5/3 mm Hg and produced no discernable reduction in the
      risk of stroke. INTERPRETATION: This blood-pressure-lowering regimen reduced the
      risk of stroke among both hypertensive and non-hypertensive individuals with a
      history of stroke or transient ischaemic attack. Combination therapy with
      perindopril and indapamide produced larger blood pressure reductions and larger
      risk reductions than did single drug therapy with perindopril alone. Treatment
      with these two agents should now be considered routinely for patients with a
      history of stroke or transient ischaemic attack, irrespective of their blood
      pressure.

PMID- 11589933
TI  - Squamous-cell cancer of the skin in patients given PUVA and ciclosporin: nested
      cohort crossover study.
AB  - BACKGROUND: Immunosuppressive treatments have been associated with an increased
      risk of skin cancer, especially in patients who have had organ transplants. We
      aimed to assess the risk of skin cancer in patients taking the ciclosporin who
      had been exposed to psoralen and ultraviolet-A light (PUVA) and other treatments
      for severe psoriasis. METHODS: We did a nested cohort crossover study of 28
      participants in the PUVA follow-up study who were on ciclosporin to compare the
      frequency of squamous-cell carcinoma before and after first use of ciclosporin.
      We also analysed the entire PUVA study cohort (1380) to assess the relation
      between use of this drug and frequency of squamous-cell carcinoma. FINDINGS: In
      the 5 years before first use, six of 28 (21%) ciclosporin users developed a total
      of 20 squamous cell cancers. After ciclosporin use (average follow-up 6 years),
      13 (46%) developed a total of 169 squamous-cell carcinomas. In the nested cohort,
      after adjustment for amount of exposure to PUVA and methotrexate, incidence of
      tumours was seven times higher after first ciclosporin use than in the previous 5
      years (incidence rate ratio 6.9 [95% CI 4.3-11]). Multivariate analysis of the
      entire cohort showed that risk of squamous-cell carcinoma after any use of
      ciclosporin is close to that recorded for at least 200 PUVA treatments (3.1 [2.6
      3.7] and 2.8 [2.6-3.2], respectively). INTERPRETATION: The risk of squamous cell
      cancer of the skin is increased by ciclosporin in patients with psoriasis who
      have been exposed to PUVA. Such risks should be balanced against the
      effectiveness of the drug and possible newer immunosuppressive agents.

PMID- 11589934
TI  - When to initiate dialysis: effect of proposed US guidelines on survival.
AB  - BACKGROUND: Recent guidelines from the US National Kidney Foundation Dialysis
      Outcomes Quality Initiative recommend an earlier start of dialysis treatment than
      has been common practice. Their implementation would have a substantial effect on
      patients' daily lives and would increase costs. The guidelines are largely
      opinion-based, because evidence is still lacking. METHODS: As part of a
      prospective multicentre study in the Netherlands, we included, between January,
      1997, and May, 1999, all new patients with end-stage renal disease, for whom data
      were available on residual renal function 0-4 weeks before the start of dialysis.
      We recorded date of death or censoring until August, 2000. FINDINGS: 94 (37%) of
      253 patients started dialysis treatment later than recommended by the US
      guideline. There was an increased mortality risk for these patients compared with
      those who started dialysis on time, although it was not significant (adjusted
      hazard ratio 1.66 [95% CI 0.95-2.89]). The adjusted difference in estimated
      survival time after 3 years on dialysis treatment was 2.5 months (1.1-4.0) in
      favour of timely starters. Conversely, the average delay in dialysis initiation
      for late starters, the extra time free of dialysis, was at least 4.1 months.
      INTERPRETATION: Although we observed a gain in survival time with a timely start
      of dialysis, it is probably a reflection of initiating dialysis earlier in the
      disease. We question the benefit of putting this guideline into daily practice,
      given the current clinical evidence and the effects it would have on patients and
      dialysis resources.

PMID- 11589936
TI  - Do better family planning services reduce abortion in Bangladesh?
AB  - BACKGROUND: Fertility decline is often associated with an increase in
      contraception and abortion, but the causal relations are difficult to examine
      with non-experimental data. We aimed to assess the effects of family planning
      services on abortion rates in two similar areas. METHODS: We examined trends in
      overall abortion rates and rates for intended and unintended pregnancies in two
      similar areas typical of rural Bangladesh. We analysed Matlab Demographic
      Surveillance System (DSS) data on pregnancy outcomes between 1979 and 1998 in
      these areas, matching them to survey data on fertility preferences, which enabled
      us to identify pregnancies as intended or unintended. FINDINGS: Abortion rates
      were significantly lower in the area with better family planning services
      compared with the comparison area (1984-86, 2.2 vs 5.2; 1996-98, 2.3 vs 6.8).
      Abortion of unintended pregnancies is similar in both areas, but the higher
      levels of contraceptive use in the treatment area have led to lower levels of
      unintended pregnancy and abortion. The likelihood that an unintended pregnancy
      will be aborted has increased in both areas but the decrease in unintended
      pregnancies was sufficiently large in the treatment area to offset this increase.
      INTERPRETATIONS: Abortion may increase during the fertility transition in less
      developed countries as the desire to limit family size increases unless there is
      widespread availability of quality family planning services.

PMID- 11589937
TI  - Development and implementation of a new rapid aneuploidy diagnostic service
      within the UK National Health Service and implications for the future of prenatal
      diagnosis.
AB  - BACKGROUND: Prenatal diagnosis for chromosome abnormality is routinely undertaken
      by full karyotype analysis of chromosomes from cultured cells; pregnant women
      must wait on average 13-14 days for their results. Autosomal trisomies, which
      account for around 80% of significant abnormalities, can be detected by
      quantitative fluorescence (QF) PCR. We report on the development and
      implementation of this technique as the first such routine service within a
      diagnostic department of the UK National Health Service (NHS). METHODS: We
      designed a "one-tube test" comprising four primer pairs for polymorphic
      tetranucleotide repeat sequences on chromosome 21, four primer pairs for
      sequences on chromosome 18, three primer pairs for sequences on chromosome 13,
      and one primer pair to identify the sex chromosomes. All prenatal samples
      received by our NHS diagnostic department between April, 2000, and April, 2001,
      were tested. After DNA extraction, PCR amplification was done and the products
      separated on a capillary-based genetic analyser; the results were interpreted
      with dedicated software. Follow-up karyotype analysis was done on all samples.
      FINDINGS: 1148 amniotic fluid samples, 188 chorionic villus samples, and 37 fetal
      tissue samples were tested; the amplification failure rate was zero with our
      current protocol. QF-PCR results were obtained and reported on 1314 (98%) of the
      prenatal samples; the remaining 22 (2%) were uninformative because of maternal
      cell contamination. One case of mosaicism in a chorionic villus sample, and two
      cases indicating somatic expansion of a tetranucleotide repeat were found. No
      false positive or false negative results were obtained. The mean reporting time
      for the last 4 months of data collection was 1.25 working days. INTERPRETATION:
      QF-PCR aneuploidy testing is an efficient and accurate technique for the
      detection of autosomal trisomies in prenatal samples. Implementation of this
      service has led to the rapid diagnosis of abnormalities and early reassurance for
      women with normal results.

PMID- 11589938
TI  - Severe pulmonary hypertension in an infant with achondroplasia.

PMID- 11589939
TI  - Neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency.
AB  - Neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency has
      not yet been introduced in the UK, primarily because of uncertainty about the
      natural history of the disorder and concerns about the specificity of the
      screening test. To obtain data on these issues, we did a retrospective study in
      which we analysed the concentrations of acylcarnitines in stored neonatal blood
      spots, and reviewed patients with high octanoylcarnitine concentrations at age 7
      9 years. The high morbidity and mortality associated with the disorder, and the
      specificity of acylcarnitine analysis seen in our study support the introduction
      of screening for MCAD deficiency.

PMID- 11589940
TI  - Blood lipid concentrations and risk of myocardial infarction.
AB  - In western countries, individuals with plasma lipid concentrations above a set
      threshold value are judged to be at risk of coronary heart disease. However, in
      Algeria, people tend to have lower lipid concentrations than those in the
      developed world, and might, therefore, be excluded from preventive strategies and
      denied treatment. We did a study in Algeria in which we investigated the plasma
      lipid profiles of 67 individuals who had had a myocardial infarction, and 70
      controls. We compared our results with those of two other similar studies done in
      France and Ireland. An increase in concentration of total cholesterol and LDL
      cholesterol, and a decrease in HDL cholesterol, was associated with raised risk
      of myocardial infarction in our study, but lipid concentrations rarely reached
      the recommended threshold values. However, cholesterol ratios (total/HDL,
      LDL/HDL) provided consistent and comparable estimates of cardiovascular risk
      across the three populations. Our results raise the question of whether threshold
      recommendations for cardiovascular risk prevention, in populations with low
      concentration of plasma lipids, should be made.

PMID- 11589941
TI  - Plasmodium falciparum cross-resistance between trimethoprim and pyrimethamine.
AB  - Trimethoprim-sulfamethoxazole has been recommended as part of the standard
      package of care for people with HIV and AIDS in Africa. A similar antifolate
      combination, sulfadoxine-pyrimethamine, is now the first-line antimalarial drug
      in several of the African countries with the highest rates of HIV infection. We
      present evidence of Plasmodium falciparum cross-resistance between trimethoprim
      and pyrimethamine at the molecular level. The impact of trimethoprim
      sulfamethoxazole on the efficacy of sulfadoxine-pyrimethamine needs to be
      assessed urgently, and alternative antimalarial treatment should be considered
      for people on trimethoprim-sulfamethoxazole prophylaxis.

PMID- 11589942
TI  - Dedifferentiation of epidermal cells to stem cells in vivo.
AB  - The effects of growth factors on wound healing have been studied extensively;
      however epidermal regeneration is not fully understood. We treated eight patients
      with leg ulcers with recombinant human epidermal growth factor (rhEGF) and
      compared biopsies of regenerating epidermis with those of controls who did not
      receive rhEGF. We used immunohistochemistry to identify cells expressing keratin
      19 and beta1 integrin in regenerated epidermis from patients and controls.
      Patients treated with rhEGF had stem cells in the spinous and granular layers of
      regenerated epidermis. Histological analysis showed that these stem cells had
      reverted from differentiated to undifferentiated stem cells. Our findings provide
      evidence for epidermal cell reversion.

PMID- 11589943
TI  - Health and safety of Afghans hangs in the balance.

PMID- 11589945
TI  - Attacks heighten US concern about threat of bioterrorism.

PMID- 11589946
TI  - Vitamin A and its impact on human medicine.

PMID- 11589947
TI  - Business as usual at UK party conferences?

PMID- 11589948
TI  - Transatlantic, robot-assisted telesurgery deemed a success.

PMID- 11589949
TI  - US guidelines on secondary prevention of cardiovascular disease updated.

PMID- 11589953
TI  - Antioxidants improve brain function in advanced renal failure.

PMID- 11589955
TI  - Apology to Dr Wafa Mohammed Khalil Fageeh, obstetrician and gynaecologist and
      assistant professor at King Abdilaziz University, and her medical team.

PMID- 11589957
TI  - Irish government launches health R&D initiative.

PMID- 11589964
TI  - The art of anaesthesia.

PMID- 11589958
TI  - Advances in hereditary deafness.
AB  - Progress in the Human Genome Project, availability of cochlea-specific cDNA
      libraries, and development of murine models of deafness have resulted in rapid
      discovery of many loci and corresponding genes for deafness. Up to now, the
      chromosomal locations of about 70 genes for non-syndromic deafness have been
      mapped, and the genes of more than 20 loci have been identified and
      characterised. Mutations in one gene, connexin 26 (CX26GJB2), are responsible for
      most cases of recessive non-syndromic deafness, accounting for 30-40% of all
      childhood genetic deafness in some populations (eg, white people of western
      European descent). We summarise advances in identification of genes for deafness
      and provide a guide to the clinical approach to diagnosis of patients with
      hearing loss.

PMID- 11589966
TI  - Biosynthesis of polyhydroxyalkanoate copolyester containing cyclohexyl groups by
      Pseudomonas oleovorans.
AB  - Production of polyhydroxyalkanoates (PHAs) substituted with cyclohexyl groups by
      Pseudomonas oleovorans grown with 4-cyclohexylbutyric acid (4-CHB) and its
      mixtures with nonanoic acid (NA) was investigated. Addition of NA to medium gave
      rise to an increase in the total concentration of 3-hydroxy-4-cyclohexylbutyrate
      repeating unit in the PHAs, indicating that the bioconversion rate of 4-CHB to
      polyester was significantly improved by the cometabolic effect. Increasing the
      proportion of NA from 1.0 to 7.5 mM at a concentration of 10 mM total carbon
      substrate also accelerated the uptake speed of 4-CHB by the organism and resulted
      in an increase of the ratio of 3-hydroxynonanoate to 3-hydroxyheptanoate from
      1.28 to 2.05. Differential scanning calorimetric analysis of the PHAs bearing the
      corresponding functional groups showed one melting transition and one glass
      transition temperature varying according to the composition. These results
      indicated that random copolyesters were obtained from the carbon substrates used
      in this study.

PMID- 11589967
TI  - Alpha and beta mechanical dispersions in high sugar/acyl gellan mixtures.
AB  - The real (G') and imaginary (G") components of the complex modulus have been
      measured between 0.1 and 100 rad/s in the temperature range of 70--55 degrees C
      for a mixture of 1% high acyl gellan with 79% glucose syrup, and 79% glucose
      syrup. The method of reduced variables gave superposed curves of G' and G" as a
      function of timescale of measurement, which matched the thermal profiles of shear
      modulus obtained by scanning at the constant rate of 1 degrees C/min. Data of the
      gellan/co-solute mixture could be analysed in terms of two distinct mechanisms.
      For the alpha dispersion, G' and G" superposed with the horizontal reduction
      factor a(T) whose temperature dependence followed an equation of the Williams
      Landel-Ferry form. Mechanical spectra of the beta dispersion also superposed with
      the factor a(T) whose temperature dependence, however, corresponded to a constant
      energy of activation. Relaxation spectra have been calculated for both
      dispersions. Those for the alpha mechanism were attributed to the chain backbone
      motions and the friction coefficient per tetrasaccharide repeat unit in backbone
      motion was calculated from the extended Rouse theory. When the contribution of
      the solvent alone was studied, no spectra for the beta dispersion were observed
      supporting the hypothesis of the dispersion being attributed to the side-chain
      motions of the acyl groups. The spectra of the beta mechanism were relatively
      broader than for the alpha dispersion. The relative location of the beta
      dispersion on the time scale or temperature range was found to be between the
      alpha dispersion (glass transition region) and the glassy state.

PMID- 11589968
TI  - Spectroscopic and molecular dynamics simulation studies of the interaction of
      insulin with glucose.
AB  - The interaction between monomeric insulin and monosaccharides has been
      investigated through circular dichroism, fluorescence spectroscopy and two
      dimensional nuclear magnetic resonance. CD spectra indicate that D-glucose
      interacts with monomeric insulin whereas D-galactose, D-mannose and 2-deoxy-D
      glucose have a lower effect. Fluorescence emission was quenched at sugar
      concentrations of 5-10 mM. Titration with the different sugars produces a
      quenching of the tyrosine spectrum from which a binding free energy value for the
      insulin-sugar complexes has been evaluated. Transfer nuclear Overhauser
      enhancement NMR experiments indicate the existence of dipolar interactions at
      short interatomic distances between C-1 proton of D-glucose in the beta form and
      the monomeric insulin. Further, NMR total correlation spectra experiments
      revealed that the hormone is in the monomeric form and that upon addition of
      glucose no aggregation occurs. The interaction does not involve relevant changes
      in the secondary structure of insulin suggesting that the interaction occur at
      the side chain level. Molecular dynamics simulations and modeling studies, based
      on the dynamic fluctuations of potential binding moiety sidechains, argued from
      results of NMR spectroscopy, provide additional informations to locate the
      putative binding sites of D-glucose to insulin.

PMID- 11589970
TI  - Effect of phosphorothioate substitutions on DNA cleavage by Escherichia coli DNA
      topoisomerase I.
AB  - To evaluate the structural influence of the DNA phosphate backbone on the
      activity of Escherichia coli DNA topoisomerase I, modified forms of
      oligonucleotide dA(7) were synthesized with a chiral phosphorothioate replacing
      the non-bridging oxygens at each position along the backbone. A deoxy-iodo-uracil
      replaced the 5'-base to crosslink the oligonucleotides by ultraviolet (UV) and
      assess binding affinity. At the scissile phosphate there was little effect on the
      cleavage rate. At the +1 phosphate, the rectus phosphorus (Rp)-thio-substitution
      reduced the rate of cleavage by a factor of 10. At the +3 and -2 positions from
      the scissile bond, the Rp-isomer was cleaved at a faster rate than the sinister
      phosphorus (Sp)-isomer. The results demonstrate the importance of backbone
      contacts between DNA substrate and E. coli topoisomerase I.

PMID- 11589969
TI  - Structural features of a water soluble gum polysaccharide from Murraya paniculata
      fruits.
AB  - A water soluble gum polysaccharide was isolated from Murraya paniculata fruits.
      Hydrolytic experiments, methylation analysis, periodate oxidation studies and NMR
      data revealed that the polysaccharide was extensively branched and it consisted
      of 1,3-, and 1,3,6-linked beta-D-galactopyranosyl units, terminal beta-D
      galactopyranosyl units and terminal alpha-D-glucopyranosyl 1,4-beta-D
      galactopyranosyl units. Small amounts of 4-O-methylglucuronic acid residues were
      also present.

PMID- 11589971
TI  - Associative phenomena in galactomannan-deacetylated xanthan systems.
AB  - The interaction between mesquite seed galactomannan (MSG; D-mannose to D
      galactose ratio (M/G) approximately 1.1) and deacetylated xanthan (DX) in 5 mM
      NaCl leading to synergistic gel formation at 25 degrees C was investigated and
      compared with the far more studied system made of xanthan and locust bean gum
      (LBG; M/G approximately 3.5). Rheology and differential scanning calorimetry were
      used to measure temperatures of gel formation and transition enthalpy as a
      function of polymer composition, while circular dichroism was used to probe the
      conformation of DX in the LBG-DX system. MSG and DX associate at 25 degrees C
      with a well defined stoichiometry of 0.6:1.0 (w/w) at low ionic strength
      favouring the disordered coil state of DX. When LBG was used in place of MSG in
      water or 5 mM NaCl, two types of mechanisms of interpolymeric association are
      envisaged.

PMID- 11589972
TI  - Structure of Acetobacter cellulose composites in the hydrated state.
AB  - The structure of composites produced by the bacterium Acetobacter xylinus have
      been studied in their natural, hydrated, state. Small-angle X-ray diffraction and
      environmental scanning electron microscopy has shown that the ribbons have a
      width of 500 A and contain smaller semi-crystalline cellulose microfibrils with
      an essentially rectangular cross-section of approximately 10 x 160 A(2).
      Incubation of Acetobacter in xyloglucan or pectin results in no changes in the
      size of either the microfibrils or the ribbons. Changes in the cellulose crystals
      are seen upon dehydration of the material, resulting in either a reduction in
      crystal size or an increase in crystal disorder.

PMID- 11589973
TI  - Spider silk fibre extrusion: combined wide- and small-angle X-ray
      microdiffraction experiments.
AB  - The major and minor ampullate silks from live Nephila senegalensis
      (Tetragnathidae) and the major ampullate silk from Euprostenops spp. (Pisauridae)
      spiders were investigated in situ by X-ray diffraction during forced silking.
      Wide- (WAXS) and small-angle (SAXS) scattering patterns were obtained at the same
      time. WAXS data show that the thread at the exit of the spigots already contains
      beta-sheet poly(alanine) crystallites. SAXS data suggest the presence of
      microfibrils with an axial repeating period of approximately 8 nm for both
      Nephila and Euprostenops. Minor ampullate (MI) Nephila silk, however, does not
      show this axial repeat which is probably due to a higher amount of crystal
      forming poly(alanine). A microfibrillar morphology, connected by a network of
      random polymer chains, can explain the presence of highly oriented crystallites,
      an oriented halo and a diffuse background in the WAXS patterns. At high reeling
      speeds, bound water is co-extruded with the fibre. It can be squeezed out of the
      fibre by friction at a needle. Under natural conditions it is the spider's tarsal
      claws which might serve to squeeze out the water to improve the mechanical
      properties of the thread during dragline production.

PMID- 11589974
TI  - Muscle contraction: viscous-like frictional forces and the impulsive model.
AB  - Apart from a few experimental studies muscle viscosity has not received much
      recent analytical attention as a determinant of the contractile process. This is
      surprising, since any muscle cell is 80% water, and may undergo large shape
      changes during its working cycle. Intuitively, one might expect the viscosity of
      the solvent to be an important determinant of the physiological activity of
      muscle tissue. This was apparent to pioneers of the study of muscle contraction
      such as Hill and his contemporaries, whose putative theoretical formulations
      contained terms related to muscle viscosity. More recently, though, a
      hydrodynamic calculation by Huxley, using a solvent viscosity close to that of
      water, has been held to demonstrate that viscous forces are negligible in muscle
      contraction. We have re-examined the role of viscosity in contraction,
      postulating impulsive acto-myosin forces that are opposed by a viscous resistance
      between the filaments. The viscous force required, 10(4) times the hydrodynamic
      estimate, is close to recent experimental measurements, themselves 10(2)-10(3)
      times the hydrodynamic estimate. This also agrees with contemporary measurements
      of cytoplasmic viscosity in other biological cells using magnetic bead micro
      rheometry. These are several orders of magnitude greater than the viscosity of
      water. In the course of the analysis, we have derived the force-velocity equation
      for an isolated half-sarcomere containing a single actin filament for the first
      time, and from first principles. We conclude that muscle viscosity is indeed
      important for the contractile process, and that it has been too readily
      discounted.

PMID- 11589975
TI  - A comparison of cortisporin and ciprofloxacin otic drops as prophylaxis against
      post-tympanostomy otorrhea.
AB  - Myringotomy and tube insertion, a common pediatric surgical procedure, is
      frequently complicated by purulent otorrhea. Many otolaryngologists routinely use
      topical antibiotics as prophylaxis against post-tympanostomy otorrhea. The
      aminoglycosides (neomycin sulfate, tobramycin and gentamicin) contained in
      commonly used topical antibiotics as well as components of the solutions have
      been shown to be ototoxic in animal studies. Although little reported evidence of
      ototoxicity in humans exists, sporadic reports of sensorineural hearing loss
      linked to topical antibiotic use do exist, and the potential for sensorineural
      hearing loss must be considered. The purpose of this study is to compare the rate
      of post-tympanostomy otorrhea in a double-blinded randomized trial using either
      topical Ciprofloxacin, with no reported ototoxicity, or Cortisporin as
      prophylaxis. One hundred patients (200 ears) between ages 7 months and 11 years
      with a diagnosis of recurrent otitis media or chronic otitis media undergoing
      tympanostomy tube insertion were randomized into two equal groups. Three drops of
      either drop A or B were placed into each ear at the time of tube insertion and
      then three times daily for 3 days. Patients were examined at 3 weeks and details
      of otorrhea were obtained. The rate of otorrhea was analyzed using chi-square.
      The overall rate of otorrhea was 39 ears (19.5%), 17 (17%) ears for the
      Cortisporin group and 22 (22%) for the Ciprofloxacin group. The difference in
      rate of otorrhea was not statistically significant (P=0.372, 95% confidence
      interval equals -6-16%). Our data suggest that topical Cortisporin offers no
      benefit over Ciprofloxacin for post-operative otorrhea prophylaxis. Therefore we
      recommend topical quinolone prophylaxis, which should eliminate concerns about
      ototoxicity, without sacrificing efficacy.

PMID- 11589976
TI  - Communication development in young deaf children: review of the video analysis
      method.
AB  - It is widely recognised that preverbal communication skills underpin development
      of spoken language. This historical review outlines the establishment of a
      quantitative methodology for assessing preverbal communication skills in children
      with hearing aids and cochlear implants. The method is shown to be reliable and
      free from observer bias. The review also summarises findings from a series of
      cross-sectional and longitudinal observational studies utilising the methodology.
      Profoundly deaf young children, either with cochlear implants or successful users
      of hearing aids, show similar patterns of preverbal communication development
      that contrast with those of unsuccessful hearing-aid users. Preverbal measures
      obtained 12 months after implantation are predictive of late performance on
      speech perception tasks. Moreover, there is a significant association between the
      preverbal measure of 'autonomy' obtained before implantation and later speech
      perception performance. This latter finding has important theoretical
      implications for understanding of language development and suggests that
      intervention that promotes autonomy in adult-child interaction may lead to
      improved outcomes. Such intervention could be commenced as soon as deafness is
      discovered.

PMID- 11589977
TI  - Endoscopic sinus surgery in cystic fibrosis: do patients benefit from surgery?
AB  - OBJECTIVE: To examine the effects of endoscopic sinus surgery on the pulmonary
      status of cystic fibrosis (CF) patients through the objective parameters of
      steroid use, pulmonary function tests (PFTs), and inpatient hospital days (IHDs).
      METHODS: Retrospective chart review of all patients with CF who underwent
      endoscopic sinus surgery from 1993 to 1999 at a tertiary care children's
      hospital. Preoperative pulmonary function, inhaler and steroid use, and IHDs were
      compared to postoperative parameters within a 1-year period. RESULTS: Sixty-six
      patients, including eight lung transplant patients, underwent a total of 112
      endoscopic sinus surgery procedures; 25 patients underwent more than one
      procedure. Patients were taking oral steroids preoperatively in 28% of procedures
      and inhaled steroids in 40%. Postoperatively, there was no statistically
      significant change in oral or inhaled steroid use, or in postoperative pulmonary
      function. If the index hospitalization, which was often for reasons not related
      to sinus disease, was considered part of the preoperative time period, endoscopic
      sinus surgery (ESS) was noted to result in a marked reduction (9.5 days
      (adjusted), P=0.001) in hospital days during the subsequent 6 months. If the date
      of the procedure alone was used to define pre- and postoperative time periods,
      the reduction in postoperative days was more modest and not statistically
      significant (3.5 days (adjusted), P=0.21). CONCLUSIONS: Although we found no
      statistically significant difference in PFTs, or steroid requirements following
      ESS, ESS may have resulted in a reduced need for hospitalization in the 6 months
      following the procedure. Future prospective studies in a larger number of
      patients and using more detailed outcome measures are needed to better evaluate
      the effects of endoscopic sinus surgery in pediatric patients with CF.

PMID- 11589978
TI  - Surgery required to verify atypical mycobacterial infections.
AB  - To estimate the incidence and distribution of nontuberculuous mycobacterial
      surgery, a retrospective case record study of 42 children operated for
      cervicofacial atypical mycobacterial infections in Oslo from 1990 to 2000 was
      performed. Mean age at diagnosis was 41 months and mean duration of the disease
      was 40 weeks from symptom onset to remission. All presented with localized and
      unilateral disease without increased hematological parameters. The majority of
      children had one lesion localized in the submandibular region characterized by
      changes in the overlying skin color, but without necrosis or fistula formation.
      Children below three significantly more often presented with only one lesion and
      the referring physician more frequently suspected neoplasm and bacterial adenitis
      than reactive adenopathy in this group. Compared to older children, there was a
      tendency for shorter symptom duration prior to outpatient treatment (mean 4 and
      13 weeks for children up to 3 and above 3 years, respectively, t=-1.6, P=0.11).
      Furthermore, mycobacterial cultures and histopathology from surgical specimens
      was needed to diagnose the disease correctly. Fine-needle aspiration biopsy was
      unsuccessful in 27% (n=8) of the patients, due to non-cooperative patients (n=2)
      or inconclusive material (n=6), and mycobacterial growth was not obtained in any
      of the samples. Intradermal mycobacteria skin testing yielded 29% (n=10) false
      negatives. Although mycobacteria was correctly diagnosed in the remaining
      patients, correct specimen was found in only 31% (n=11) of the 25 cases.

PMID- 11589979
TI  - The site of the hearing loss in Refsum's disease.
AB  - Refsum's disease is a disorder of lipid metabolism with pigmentary retinopathy,
      demyelinating neuropathy, ataxia, and hearing loss. Previous histological studies
      have located the site of hearing impairment in the inner ear, but it has never
      been confirmed audiologicaly in the literature. In this reported case of Refsum's
      disease, despite hearing loss and absence of response in ABR, robust otoacoustic
      emissions were measured. Together with these and other audiological findings, we
      conclude that our case might be the first reported case of Refsum's disease with
      auditory neuropathy. The site of the hearing abnormality in Refsum's disease may
      be 'post-outer hair cells' in some cases as in the current case. Because of their
      limited benefits and risk of noise-induced damage to outer hair cells, the use of
      hearing aids before otoacoustic emission measurements should be considered
      cautiously in Refsum's disease.

PMID- 11589980
TI  - Efficacy of topotecan treatment on an experimental model of transient evoked
      otoacoustic emissions.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of topotecan
      (Hycamtin), a topoisomerase I inhibiting anticancer agent, on Transient Evoked
      Otoacoustic Emissions (TEOAEs) of the rabbits. We planned to investigate whether
      this test might provide a method for monitoring early ototoxic influence of drug
      administration to the cochlea. METHODS: The study was conveyed in two groups each
      consisting of five rabbits with a total of ten ears. Rabbits in group I received
      i.v. topotecan (0.5 mg/kg once daily) for 3 days. Rabbits in group II received
      i.v. topotecan (0.25 mg/kg once daily) for 3 days. Cochlear function was serially
      monitored using transient evoked otoacoustic emissions before administration (BA)
      and on the 4th and 15th days after administration of topotecan. TEOAEs were
      analysed in terms of mean stimulus, stability and emission amplitude at 1.0-4.0
      kHz. RESULTS: For group I and II, intergroup and intragroup differences were not
      statistically significant in the mean stimulus, stability and emission amplitudes
      at 1.0-4.0 kHz. CONCLUSIONS: We evaluated the potential role of TEOAEs in early
      identification of cochlear dysfunction induced by topotecan. It was concluded
      that topotecan did not have ototoxic effects on the cochlea in the early period
      of administration. TEOAEs may be useful to monitor the cochlear function and to
      detect the late stage of ototoxicity especially in the presence of potentially
      toxic factors for the prevention of permanent damage.

PMID- 11589981
TI  - Mucocele of the anterior lingual salivary glands: from extravasation to an
      alarming mass with a benign course.
AB  - Mucoceles are common cystic lesions in the oral cavity. However, mucoceles
      located on the ventral surface of the tongue originating from anterior lingual
      salivary glands are rare. Only 24 cases were reported in the medical literature,
      of which most were relatively small lesions measuring less than 20 mm in
      diameter. This report describes a large-sized mucocele of the anterior lingual
      salivary glands in an 8-year-old boy who was treated by surgical excision of the
      lesion. The authors emphasize the importance of preoperative awareness and en
      bloc excision of the lesion even in asymptomatic patients to avoid further
      enlargement and complications.

PMID- 11589982
TI  - Pai syndrome: a report of a case and review of the literature.
AB  - Pai syndrome is a rare congenital disorder first described in 1987. The main
      clinical features of the syndrome include median cleft of the upper lip, intra
      cranial lipoma, and cutaneous polyps. Only four cases have been described
      previously. This is the fifth who is a twin of Arabian descent to be reported.
      Full description of the clinico-pathological features and a review of the
      relevant medical literature is presented. To the best of our knowledge, this is
      the first case of Pai syndrome in a twin in the English literature.

PMID- 11589983
TI  - Aneurysm of the internal carotid artery following soft tissue penetration injury.
AB  - Aneurysms of the extracranial arteries are in most cases secondary to
      atherosclerosis but may also be due to degeneration, congenital abnormalities,
      trauma or unclear etiology. They present either with bulging in the lateral
      pharyngeal wall or the neck. Therefore, otolaryngologists are often among the
      first physicians to see the patient. In this report, we present a case of
      spontaneous oral bleeding that was caused by a pseudoaneurysm following 2 weeks
      after a soft tissue penetration injury in a child. The facial swelling of the
      child was initially diagnosed to be mumps by its pediatrician and the fever
      treated with aspirin. A pseudonaneurysm of the internal carotid artery was
      identified by arteriography as the source of the abrupt oral bleeding and
      required immediate surgical treatment including radiological means. Our report
      should illustrate the importance of careful preoperative evaluation as well as a
      high index of suspicion especially in children, where evaluation of history is
      difficult.

PMID- 11589984
TI  - Inflammatory myofibroblastic tumor of the nasal cavity: a case report and review
      of the literature.
AB  - Our aim is to describe clinicopathological, histochemical, and
      immunohistochemical findings of one case of inflammatory myofibroblastic tumor of
      the nasal cavity. A 10-year-old female presented with a short history of nasal
      obstruction, epistaxis, nasal discharge and headache. Computerized tomography
      (CT) scans showed a space-occupying lesion in the right nasal cavity.
      Histological examination of initial biopsy showed fascicles of spindle cells in a
      mixed inflammatory background with a predominance of plasma cells, typical of
      inflammatory pseudotumor. The spindle cells were positive for vimentin and actin.
      The mass was completely excised without any difficulty under generalized
      anesthesia. Inflammatory myofibroblastic tumor of the nasal cavity is a localized
      and completely benign lesion. Simple complete excision is curative.

PMID- 11589985
TI  - Congenital cholesteatoma of the tympanic membrane.
AB  - We present two cases of congenital cholesteatoma of the tympanic membrane.
      Congenital cholesteatoma within the tympanic membrane is a rare entity with only
      few cases documented. The aetiopathogenesis of this lesion is still unknown. An
      embryologic origin is hypothesized when cholesteatoma develops in patients
      without previous history of otitis as in the two cases we report. In cases with
      previous history of inflammatory process of the external or middle ear an
      acquired origin is suspected due to the proliferation of the basal cell layer of
      the tympanic membrane epithelium. Despite the rarity of the congenital tympanic
      membrane cholesteatoma, we think that its early diagnosis is of utmost importance
      to allow an easy removal and avoid middle ear involvement.

PMID- 11589986
TI  - Bezold's abscess in children: case report and review of the literature.
AB  - The introduction of antibiotics in the treatment of suppurative otitis media has
      significantly decreased the incidence of complications. Reports of Bezold's
      abscess secondary to this disorder are rare, particularly in infants and young
      children, in whom mastoid bone pneumatization is not yet complete. We present a
      case of Bezold's abscess occurring in a child aged 18 months. The literature is
      reviewed and methods to accurately diagnose this complication are emphasized.

PMID- 11589987
TI  - Proboscis lateralis: a case report.
AB  - Proboscis lateralis is a rare facial anomaly resulting in incomplete formation of
      one side of the nose. We report a left-sided proboscis lateralis case of a 9
      months old male with left-sided heminasal aplasia, microphthalmi, coloboma iris
      and retina and an arachnoid cyst in the temporal fossa of the brain. We present
      the clinical, radiological features of this unusual case.

PMID- 11589988
TI  - A comparative study of three cranial sensory ganglia projecting into the oral
      cavity: in situ hybridization analyses of neurotrophin receptors and
      thermosensitive cation channels.
AB  - Peripheral cranial sensory nerves projecting into the oral cavity receive food
      intake stimuli and transmit sensory signals to the central nervous system. To
      describe and compare the features of the cranial sensory ganglia that innervate
      the oral cavity, i.e., the trigeminal, petrosal, and geniculate ganglia (TG, PG,
      and GG, respectively), in situ hybridization was conducted using riboprobes for
      neurotrophin receptors (TrkA, TrkB, and TrkC), a neurotransmitter (substance P),
      and ion channels important for thermosensation (VR1 and TREK-1). In TG, all in
      six probes yielded positive signals to various extent in intensity and frequency.
      In addition, a strong correlation between the expression of VR1 and those of TrkA
      and substance P was observed as in the case of the dorsal root ganglia. In PG,
      positive signals to all six probes were also detected, and the correlation of
      expression was similar to that shown by TG. On the other hand, most cells in GG
      were positive to the TrkB probe, and a small number of cells were positive to the
      TrkC probe, but no significant signal was observed for the other four probes.
      These results indicate that TG and PG consist of cells that are heterogeneous in
      terms of neurotrophin requirement and somatosensory functions, and that GG seems
      to consist mainly of a homogeneous cell type, gustatory neurons. In conclusion,
      TG, PG, and GG, show gene expression characteristics intrinsic to the three
      ganglia. It is also concluded that TG and a portion of PG project several types
      of somatosensory nerves. This is consistent with the finding that GG and a
      portion of PG project gustatory nerves.

PMID- 11589989
TI  - Dynamics of c-fos and ICER mRNA expression in rat forebrain following lithium
      chloride injection.
AB  - Lithium is commonly used as a treatment for affective disorders in humans and as
      a toxin to produce conditioned taste aversions in rats. LiCl administration in
      rats has been correlated with activation of c-fos and cAMP-mediated gene
      transcription in many brain regions; however, little is known about the timing or
      duration of gene activation. We hypothesized that c-fos gene transcription is
      rapidly stimulated by LiCl, followed later by the expression of the inducible
      cAMP early repressor (ICER) transcription factor, a negative modulator of cAMP
      mediated gene transcription. By in situ hybridization, we analyzed the timecourse
      of c-fos and ICER mRNA expression in the central nucleus of the amygdala (CeA),
      the paraventricular nucleus of the hypothalamus (PVN) and the supraoptic nucleus
      (SON) at seven time points (0, 0.3, 1, 3, 6, 9 and 12 h) after intraperitoneal
      LiCl injection (0.15 M, 12 ml/kg, 76 mg/kg). Expression of c-fos mRNA peaked
      between 20 min and 1 h and returned to baseline by 3 h in the CeA, PVN and SON.
      ICER mRNA was detected in these regions at 20 min, peaked at 1-3 h and returned
      to nearly baseline 9 h following LiCl injection. The time lag between c-fos mRNA
      expression and ICER mRNA expression within the same regions is consistent with
      ICER terminating c-fos gene transcription. However, no refractory period was
      detected for restimulation of c-fos transcription by a second injection of LiCl
      during the period of peak ICER mRNA expression, suggesting the involvement of
      other transcriptional modulators.

PMID- 11589990
TI  - Enhanced auditory reversal learning by genetic activation of protein kinase C in
      small groups of rat hippocampal neurons.
AB  - The hippocampus has a central role in specific types of learning, but there is
      only limited evidence identifying the requisite molecular changes in ensembles of
      hippocampal neurons. To investigate the role of protein kinase C (PKC) pathways
      in hippocampal mediated learning, a constitutively active, catalytic domain of
      rat PKC betaII was delivered into hippocampal dentate granule neurons using a
      Herpes Simplex Virus (HSV-1) vector. This PKC causes a long-lasting, activation
      dependent increase in neurotransmitter release from cultured cells. Activation of
      PKC pathways in a small percentage (< or =0.26%) of dentate granule neurons was
      sufficient to enhance rat auditory discrimination reversal learning. The affected
      neurons altered hippocampal physiology as revealed by elevated NMDA receptor
      densities in specific hippocampal areas. Thus, these results directly suggest
      that activation of PKC pathways in a specific hippocampal area alters rat
      auditory discrimination reversal learning. Because each rat may contain a unique
      pattern of affected neurons, there appears to be considerable flexibility and/or
      redundancy in the groups of neurons that can modify learning.

PMID- 11589991
TI  - The floor plate cells from bovines express the mRNA encoding for SCO-spondin and
      its translation products.
AB  - The floor plate (FP) is a transient structure of the embryonic central nervous
      system (CNS) which plays a key role in development driving cell differentiation
      and patterning in the ventral neural tube. The fact that antisera raised against
      subcommissural organ (SCO) secretion immunostain FP cells and react with high
      molecular-mass proteins in FP extracts, prompted us to investigate the expression
      of a SCO-related polypeptide in FP cells. RNA from bovine FP was analyzed by
      means of reverse transcriptase polymerase chain reaction (RT-PCR), using primers
      derived from the 3' end of SCO-spondin which revealed products of 233, 237, 519
      and 783 bp. Sequence analysis of the 233 bp PCR fragment confirmed the identity
      between this FP product and SCO-spondin. FP-translation of the SCO-spondin
      encoded polypeptide(s) was demonstrated by Western blot analysis and
      immunocytochemistry, using antisera raised against (i) the glycoproteins secreted
      by the bovine SCO, and (ii) a peptide derived from the open reading frame of the
      major SCO secretory protein, SCO-spondin, respectively. Additional evidence
      pointing to active transcription and translation of a SCO-spondin related gene
      was obtained in long term FP organ cultures. On the basis of partial sequence
      homologies of SCO-spondin with protein domains implicated in cell-cell contacts,
      cell-matrix interactions and neurite outgrowth it is possible to suggest that the
      SCO-spondin secreted by the FP is involved in CNS development.

PMID- 11589992
TI  - Heat shock protein 27 shows a distinctive widespread spatial and temporal pattern
      of induction in CNS glial and neuronal cells compared to heat shock protein 70
      and caspase 3 following kainate administration.
AB  - Kainate-induced status epilepticus is associated with both apoptotic and necrotic
      cell death and induction of heat shock proteins (HSPs) in hippocampal and
      cortical regions of the rodent brain. In the present study we have examined the
      temporal, spatial and cellular expression patterns of mRNAs for the highly
      inducible HSPs, HSP70 and HSP27, together with the apoptotic marker, caspase 3
      (CPP32) in rat brain after systemic administration of kainate. HSP70 mRNA was
      transiently induced in the forebrain by kainate, principally in the CA1, CA3 and
      hilar cells of the hippocampal formation, in piriform cortex and discrete
      thalamic nuclei. Maximal expression was seen at 8 h after kainate which then
      declined to background levels by 7 days. Labelling was predominantly neuronal. In
      contrast, HSP27 mRNA expression was more widespread. Intense labelling was
      observed in CA1, CA3 and the hilar region at 8 h after kainate but the expression
      profile for HSP27 mRNA expanded considerably with intense signals seen in corpus
      callosum, cortex and thalamus at 24 h post kainate. Emulsion autoradiographs
      indicated a predominantly glial localisation for HSP27 mRNA. In the hilus, a
      distinct subpopulation of interneurones were found to express HSP27 mRNA. CPP32
      mRNA was upregulated in CA1, CA3 and hilus of the hippocampal formation and in
      piriform cortex. CPP32 mRNA expression was more restricted and similar in
      distribution to HSP70 mRNA being localised to neurones. The present study
      demonstrates the unique early expression of HSP27 mRNA by glial cells and
      distinct populations of neurones which extends beyond those in which HSP70 and
      CPP32 induction occurs with subsequent cell loss.

PMID- 11589993
TI  - Differential expression of alpha1-adrenoceptor subtype mRNAs in the dorsal root
      ganglion after spinal nerve ligation.
AB  - In spinal nerve ligated Lewis strain neuropathic rats, pain behaviors and the
      rate of ectopic discharges of injured sensory neurons were significantly reduced
      by systemic injection of phentolamine. A pharmacological study indicated that
      this adrenergic dependency was mediated by alpha(1)-adrenoceptors (alpha(1)-AR).
      The development of adrenergic sensitivity in injured sensory neurons might have
      resulted from changes in adrenoceptor expression as a consequence of changed
      expression of adrenoceptor genes. This possibility was examined by determining
      the changes in the mRNA expression of 3 subtypes of alpha(1)-ARs, alpha(1a)-,
      alpha(1b)-, and alpha(1d)-ARs, in the dorsal root ganglia (DRG) after spinal
      nerve ligation. The L4 and L5 spinal nerves were tightly ligated in Lewis rats.
      One week later, the L4 and L5 DRG were collected and RNase protection assay (RPA)
      and in situ hybridization were performed. In the DRG of unoperated rats, a
      moderate amount of alpha(1a)-AR mRNA was present while the amount of either
      alpha(1b)-AR or alpha(1d)-AR mRNA was small. After spinal nerve ligation, there
      was a significant increase in the amount of alpha(1b)-AR mRNA in the nerve
      ligated DRG as measured by RPA. The amount of alpha(1a)-AR mRNA was decreased to
      20% of the normal level while that of alpha(1d)-AR mRNA did not change. The in
      situ hybridization study showed that the number of alpha(1b)-AR mRNA positive
      neurons increased in spinal nerve ligated DRG, confirming the results of RPA
      study. These data suggest that the up-regulated expression of alpha(1b)-AR mRNA
      in axotomized DRG neurons may play an important role in the development of
      adrenergic sensitivity in injured sensory neurons and thus contribute to the
      sympathetically maintained pain in spinal nerve ligated neuropathic Lewis rats.

PMID- 11589994
TI  - Suppression subtraction hybridization and northern analysis reveal upregulation
      of heat shock, trkB, and sodium calcium exchanger genes following global cerebral
      ischemia in the rat.
AB  - Driver (sham-operated) and tester (ischemic) hippocampal cDNAs were subtracted,
      and the resulting ischemia-induced upregulated gene expression was verified by
      northern analysis. cDNAs isolated corresponded to (1) genes known to be
      upregulated following ischemia, (hsc70, hsp90, hsp105 and trkB) and (2) a gene
      not previously implicated with cerebral ischemia, sodium calcium exchanger (ncx).
      Furthermore, upregulation of these genes was demonstrated following
      preconditioning transient global ischemia.

PMID- 11589995
TI  - Selective increases in cytokine expression in the rat brain in response to
      striatal injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and
      interleukin-1.
AB  - A number of cytokines contribute to acute experimental neurodegeneration. The
      cytokine response can have detrimental or beneficial effects depending on the
      temporal profile and balance between pro- and anti-inflammatory molecules. Our
      recent data suggest that the pro-inflammatory cytokine interleukin-1beta (IL
      1beta) acts at specific sites (e.g., the striatum) in the rat brain to cause
      distant cortical injury, when co-administered with the potent excitotoxin alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionate (S-AMPA). The objective of the
      present study was to investigate changes in the expression of several cytokines
      simultaneously in the rat striatum and cortex after intrastriatal administration
      of vehicle, S-AMPA or human recombinant (hr) IL-1beta alone or S-AMPA co-injected
      with hrIL-1beta using reverse transcription-polymerase chain reaction (RT-PCR;
      Taqman fluorogenic probes) and enzyme-linked immunosorbent assay (ELISA).
      Injection of S-AMPA alone increased IL-6 mRNA expression in the ipsilateral
      striatum after 8 h, whilst striatal injection of IL-1beta alone increased local
      IL-1beta and IL-1ra mRNAs. The levels of mRNA encoding IL-1alpha, IL-1beta, IL
      1ra, IL-6, IL-10 and TNFalpha were markedly elevated in the ipsilateral cortex 8
      h after co-injection of S-AMPA and hrIL-1beta. Cortical mRNA levels for IL-4, IL
      18, TGFbeta and IFNgamma were not significantly different between treatment
      groups after 2 h or 8 h. A similar pattern of change in the levels of IL-1alpha
      and IL-6 protein was observed 8 h after treatment. These data demonstrate
      selective increases in the expression of cytokines in areas of remote cell death
      in response to administration of hrIL-1beta and S-AMPA. Such cytokines may be
      involved in the ensuing damage, and further clarification of their actions could
      aid future therapeutic strategies for several acute neurodegenerative disorders.

PMID- 11589996
TI  - Molecular events involved in neuronal death induced in the mouse hippocampus by
      in-vivo injection of kainic acid.
AB  - Apoptosis results from the activation of a programmed cellular cascade involving
      several mechanisms. In the present study, we have investigated the implication of
      three molecules of this cascade, p53, Bax and caspase-3, in neuronal death
      induced by kainic acid (KA) administration in mouse hippocampus. Using
      immunocytochemistry, western blot and quantification of enzyme activity, we
      observed in p53+/+ and p53-/- animals that KA induced neuronal death by both p53
      dependent and independent pathways. Moreover, apoptosis (labeled by TUNEL) and
      the increase of bax and caspase-3 protein expression after the neurotoxic insult
      appeared to clearly depend on p53 expression.

PMID- 11589998
TI  - Vesicular GABA transporter mRNA expression in the dentate gyrus and in mossy
      fiber synaptosomes.
AB  - In the normal granule cells of the dentate gyrus, glutamate and both gamma
      aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD) coexist. GAD
      expression is increased after seizures, and simultaneous glutamatergic and
      GABAergic neurotransmission from the mossy fibers to CA3 appears, supporting the
      hypothesis that GABA can be released from the mossy fibers. To sustain GABAergic
      neurotransmission, the amino acid must be transported into synaptic vesicles. To
      address this, using RT-PCR we looked for the presence and regulation of
      expression of the vesicular GABA transporter (VGAT) mRNA in the dentate gyrus and
      in mossy fiber synaptosomes of control and kindled rats. We found trace amounts
      of VGAT mRNA in the dentate gyrus and mossy fiber synaptosomes of control rats.
      In the dentate gyrus of kindled rats with several seizures and of control rats
      subject to one acute seizure, no changes were apparent either 1 or 24 h after the
      seizures. However, repetitive synaptic or antidromic activation of the granule
      cells in slices of control rats in vitro induces an activity-dependent
      enhancement of VGAT mRNA expression in the dentate. Surprisingly, in the mossy
      fiber synaptosomes of seizing rats, the levels of VGAT mRNA were significantly
      higher than in controls. These data show that the granule cells and their mossy
      fibers, besides containing machinery for the synthesis of GABA, also contain the
      elements that support its vesiculation. This further supports the notion that
      local synaptic molecular changes enable mossy fibers to release GABA in response
      to enhanced excitability.

PMID- 11589997
TI  - Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve
      injury.
AB  - The p38 stress-activated protein kinase pathway is involved in regulation of
      phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non
      neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were
      specifically activated in spinal motor neurons after sciatic nerve axotomy. The
      activation of the p38 kinase was required for induction of Hsp25 expression.
      Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway
      that prevents neuronal cell death. Together, our observations implicate Hsp25 as
      a central player in a complex system of signaling that may both promote
      regeneration of nerve fibers and prevent neuronal cell death in the injured
      spinal cord.

PMID- 11589999
TI  - Protein-fold evolution in the test tube.
AB  - Currently, the combination of library selection and directed evolution is the
      most powerful approach for finding proteins with novel folds or functions. In the
      past, most studies concentrated either on protein scaffolds with a given fold or
      on short peptides. With the recent development of potent in vitro selection and
      evolution techniques, the screening of much larger sequence space is possible,
      allowing for the de novo generation of proteins.

PMID- 11590000
TI  - The CHASE domain: a predicted ligand-binding module in plant cytokinin receptors
      and other eukaryotic and bacterial receptors.
AB  - A novel, 200-230 amino acid extracellular domain was identified in the plant
      cytokinin receptor Cre1, in the receptor-histidine kinase DhkA and the adenylyl
      cyclase Acg from the slime mold Dictyostelium discoideum, and in a variety of
      other receptor-like proteins from bacteria and eukaryotes. The domain is
      predicted to bind diverse low molecular weight ligands, such as the cytokinin
      like adenine derivatives or peptides, and mediate signal transduction through the
      respective receptors.

PMID- 11590001
TI  - CHASE: an extracellular sensing domain common to transmembrane receptors from
      prokaryotes, lower eukaryotes and plants.
AB  - A novel extracellular ligand-binding domain, termed CHASE, is described in
      sensory adenylyl and diguanylate cyclases, and histidine kinases, in several
      bacterial species, Dictyostelium and plants. The CHASE domain is predicted to
      sense stimuli that are specific for the developmental program of an organism.

PMID- 11590011
TI  - Aminoacyl-tRNA synthetases: potential markers of genetic code development.
AB  - Aminoacylation of tRNAs, catalyzed by 20 aminoacyl-tRNA synthetases, is
      responsible for establishing the genetic code. The enzymes are divided into two
      classes on the basis of the architectures of their active sites. Members of the
      two classes also differ in that they bind opposite sides of the tRNA acceptor
      stem. Importantly, specific pairs of synthetases--one from each class--can be
      docked simultaneously onto the acceptor stem. This article relates these specific
      pairings to the organization of the table of codons that defines the universal
      genetic code.

PMID- 11590012
TI  - Macromolecular crowding: obvious but underappreciated.
AB  - Biological macromolecules evolve and function within intracellular environments
      that are crowded with other macromolecules. Crowding results in surprisingly
      large quantitative effects on both the rates and the equilibria of interactions
      involving macromolecules, but such interactions are commonly studied outside the
      cell in uncrowded buffers. The addition of high concentrations of natural and
      synthetic macromolecules to such buffers enables crowding to be mimicked in
      vitro, and should be encouraged as a routine variable to study. The stimulation
      of protein aggregation by crowding might account for the existence of molecular
      chaperones that combat this effect. Positive results of crowding include
      enhancing the collapse of polypeptide chains into functional proteins, the
      assembly of oligomeric structures and the efficiency of action of some molecular
      chaperones and metabolic pathways.

PMID- 11590013
TI  - Structural properties of lipid-binding sites in cytoskeletal proteins.
AB  - Several cytoskeletal proteins have been shown to interact in vitro with, and in
      some cases are regulated by, specific membrane lipids. In some cases, evidence
      for in situ interactions has been provided. The molecular basis for such
      interactions is now being unravelled. At least five structurally distinct types
      of lipid-binding sites in cytoskeletal proteins have been identified. However,
      our understanding of the physiological role of such interactions is still
      limited. Precise knowledge about the binding-site structures and the actual amino
      acid residues involved should now enable the expression of mutant proteins that
      specifically lack the ability to interact with lipids. The impact of these
      mutations on protein location and function can then be assessed.

PMID- 11590014
TI  - Pressure provides new insights into protein folding, dynamics and structure.
AB  - Hydrostatic pressure is a powerful tool for studying protein folding, and the
      dynamics and structure of folding intermediates. Recently, pressure techniques
      have opened two important fronts to aid our understanding of how polypeptides
      fold into highly structured conformations. The first advance is the stabilization
      of folding intermediates, making it possible to characterize their structures and
      dynamics by different methodologies. Kinetic studies under pressure constitute
      the second advance, promising detailed appraisal and understanding of protein
      folding landscapes. The combination of these two approaches enables dissection of
      the roles of packing and cavities in folding, and in assembly of multimolecular
      structures such as protein-DNA complexes and viruses. The study of aggregates and
      amyloids, derived from partially folded intermediates at the junction between
      productive and off-pathway folding, have also been studied, promising better
      understanding of diseases associated with protein misfolding.

PMID- 11590015
TI  - Dissecting glycoprotein quality control in the secretory pathway.
AB  - In the early secretory pathway, asparagine-linked glycosylation facilitates the
      conformational maturation of diverse polypeptides by promoting their physical
      engagement with the glycoprotein-folding machinery. Misfolded glycoproteins are
      selectively eliminated from the endoplasmic reticulum by a stringent process of
      conformation-based quality control. Recent studies indicate that a small ensemble
      of oligosaccharide-processing enzymes and lectins use the asparagine-linked
      appendage to orchestrate the selective disposal of numerous transport-defective
      glycoproteins from the early secretory pathway. The glycan-based disposal system
      functions as an evolutionarily conserved terminal checkpoint in eukaryote genome
      expression. That the mechanisms by which glycoprotein substrates are recruited
      for degradation diverge at the level of signal recognition reflects a previously
      unappreciated component of cellular differentiation in higher eukaryotes.

PMID- 11590016
TI  - Immunity proteins: enzyme inhibitors that avoid the active site.
AB  - Immunity proteins are high affinity inhibitors of colicins--SOS-induced toxins
      released by bacteria during times of stress. Recent work has shown that nuclease
      specific immunity proteins are exosite inhibitors, binding adjacent to the enzyme
      active site and inhibiting colicin activity indirectly. Unusually, their binding
      sites comprise a near contiguous sequence that lies N-terminal to active site
      sequences, raising the possibility that immunity proteins bind colicins co
      translationally. Exosite binding accounts for the extensive sequence diversity
      seen at the interfaces of colicin-immunity protein complexes, which is not only a
      selective advantage to colicin-producing bacteria, but also represents a powerful
      model system for studying specificity in protein-protein recognition.

PMID- 11590017
TI  - Exploding the Pasteurian legend.

PMID- 11590018
TI  - Intramers as promising new tools in functional proteomics.
AB  - Aptamers are valuable tools for studying numerous aspects of biological
      processes, opening up new experimental opportunities to analyse the function of a
      wide range of cellular molecules. Functional RNA molecules can be rapidly
      selected in vitro from complex combinatorial mixtures of different sequences.
      Recently, it was shown that in vitro selection processes can be automated: the
      first generation selection robots will soon mean aptamers for several targets can
      be isolated in parallel within days rather than weeks. Aptamers not only exhibit
      highly specific molecular recognition properties but are also able to modulate
      the function of their cognate targets in a highly specific manner by agonistic or
      antagonistic mechanisms. These properties prompted the development of novel
      technologies to exploit the use of aptamers to modulate distinct functions of
      biological targets. Recent controlled expression of aptamers inside cells
      demonstrated their impressive potential as rapidly generated intracellular
      inhibitors of biomolecules. Intracellularly applied aptamers are also called
      'intramers'. Here we discuss recent developments and strategies for intramer
      based technologies that have the potential to greatly facilitate characterisation
      of unknown protein functions in the context of their natural expression status in
      vivo. Thus, intramer-based technologies offer many promising applications in
      functional genomics, proteomics and drug discovery.

PMID- 11590019
TI  - Selective chemical inactivation of AAA proteins reveals distinct functions of
      proteasomal ATPases.
AB  - BACKGROUND: The 26S proteasome contains six highly related ATPases of the AAA
      family. We have developed a strategy that allows selective inhibition of
      individual proteasomal ATPases in the intact proteasome. Mutation of a threonine
      in the active site of Sug1/Rpt6 or Sug2/Rpt4 to a cysteine sensitizes these
      proteins to inactivation through alkylation by the sulfhydryl modifying agent
      NEM. Using this technique the individual contributions of Sug1 and Sug2 to
      proteasome function can be assessed. RESULTS: We show that both Sug1 and Sug2 can
      be selectively alkylated by NEM in the context of the intact 26S complex and as
      predicted by structural modeling, this inactivates the ATPase function. Using
      this technique we demonstrate that both Sug 1 and 2 are required for full
      peptidase activity of the proteasome and that their functions are not redundant.
      Kinetic analysis suggests that Sug2 may have an important role in maintaining the
      interaction between the 19S regulatory complex and the 20S proteasome. In
      contrast, inhibition of Sug1 apparently decreases peptidase activity of the 26S
      proteasome by another mechanism. CONCLUSIONS: These results describe a useful
      technique for the selective inactivation of AAA proteins. In addition, they also
      demonstrate that the functions of two related proteasomal AAA proteins are not
      redundant, suggesting differential roles of proteasomal AAA proteins in protein
      degradation.

PMID- 11590020
TI  - A new plasmid display technology for the in vitro selection of functional
      phenotype-genotype linked proteins.
AB  - BACKGROUND: Display technologies which allow peptides or proteins to be
      physically associated with the encoding DNA are central to procedures which
      involve screening of protein libraries in vitro for new or altered function. Here
      we describe a new system designed specifically for the display of libraries of
      diverse, functional proteins which utilises the DNA binding protein nuclear
      factor kappa B (NF-kappa B) p50 to establish a phenotype-genotype link between
      the displayed protein and the encoding gene. RESULTS: A range of model fusion
      proteins to either the amino- or carboxy-terminus of NF-kappa B p50 have been
      constructed and shown to retain the picomolar affinity and DNA specificity of
      wild-type NF-kappa B p50. Through use of an optimal combination of binding buffer
      and DNA target sequence, the half-life of p50-DNA complexes could be increased to
      over 47 h, enabling the competitive selection of a variety of protein-plasmid
      complexes with enrichment factors of up to 6000-fold per round. The p50-based
      plasmid display system was used to enrich a maltose binding protein complex to
      homogeneity in only three rounds from a binary mixture with a starting ratio of
      1:10(8) and to enrich to near homogeneity a single functional protein from a
      phenotype-genotype linked Escherichia coli genomic library using in vitro
      functional selections. CONCLUSIONS: A new display technology is described which
      addresses the challenge of functional protein display. The results demonstrate
      that plasmid display is sufficiently sensitive to select a functional protein
      from large libraries and that it therefore represents a useful addition to the
      repertoire of display technologies.

PMID- 11590021
TI  - DNA bending by asymmetrically tethered cations: influence of tether flexibility.
AB  - BACKGROUND: We have been studying the proposal that laterally asymmetric charge
      neutralization along the DNA double helix can induce collapse toward the
      neutralized surface. Results of previous experiments implied that such a
      phenomenon can occur, suggesting a role for local interphosphate repulsive forces
      in DNA shape and rigidity. RESULTS: We now show that, whereas six ammonium ions
      tethered to one DNA face on flexible propyl chains can induce detectable DNA
      curvature, tethering of ammonium ions on rigid propynyl tethers does not induce
      DNA curvature. Molecular modeling indicates differing propensities for phosphate
      salt bridge formation between propyl- and propynyl-tethered ammonium ions.
      CONCLUSIONS: Ammonium ion localization is suggested as a key factor in induced
      bending. Rigidification of the double helix by stacking of propyne groups cannot
      be excluded.

PMID- 11590022
TI  - Predicting and harnessing protein flexibility in the design of species-specific
      inhibitors of thymidylate synthase.
AB  - BACKGROUND: Protein plasticity in response to ligand binding abrogates the notion
      of a rigid receptor site. Thus, computational docking alone misses important
      prospective drug design leads. Bacterial-specific inhibitors of an essential
      enzyme, thymidylate synthase (TS), were developed using a combination of computer
      based screening followed by in-parallel synthetic elaboration and enzyme assay
      [Tondi et al. (1999) Chem. Biol. 6, 319-331]. Specificity was achieved through
      protein plasticity and despite the very high sequence conservation of the enzyme
      between species. RESULTS: The most potent of the inhibitors synthesized, N,O
      didansyl-L-tyrosine (DDT), binds to Lactobacillus casei TS (LcTS) with 35-fold
      higher affinity and to Escherichia coli TS (EcTS) with 24-fold higher affinity
      than to human TS (hTS). To reveal the molecular basis for this specificity, we
      have determined the crystal structure of EcTS complexed with DDT and 2'
      deoxyuridine-5'-monophosphate (dUMP). The 2.0 A structure shows that DDT binds to
      EcTS in a conformation not predicted by molecular docking studies and
      substantially differently than other TS inhibitors. Binding of DDT is accompanied
      by large rearrangements of the protein both near and distal to the enzyme's
      active site with movement of C alpha carbons up to 6 A relative to other ternary
      complexes. This protein plasticity results in novel interactions with DDT
      including the formation of hydrogen bonds and van der Waals interactions to
      residues conserved in bacterial TS but not hTS and which are hypothesized to
      account for DDT's specificity. The conformation DDT adopts when bound to EcTS
      explains the activity of several other LcTS inhibitors synthesized in-parallel
      with DDT suggesting that DDT binds to the two enzymes in similar orientations.
      CONCLUSIONS: Dramatic protein rearrangements involving both main and side chain
      atoms play an important role in the recognition of DDT by EcTS and highlight the
      importance of incorporating protein plasticity in drug design. The crystal
      structure of the EcTS/dUMP/DDT complex is a model system to develop more
      selective TS inhibitors aimed at pathogenic bacterial species. The crystal
      structure also suggests a general formula for identifying regions of TS and other
      enzymes that may be treated as flexible to aid in computational methods of drug
      discovery.

PMID- 11590024
TI  - Bilosomes: the answer to oral vaccine delivery?

PMID- 11590023
TI  - Exploring the impact of different thioesterase domains for the design of hybrid
      peptide synthetases.
AB  - BACKGROUND: A large number of pharmacologically important peptides are
      synthesized by multifunctional enzymes, the nonribosomal peptide synthetases
      (NRPSs). The thioesterase (Te) domain at the C-terminus of the last NRPS
      catalyzes product cleavage by hydrolysis or complex macrocyclization. Recent
      studies with excised Te domains and peptidyl-S-N-acetyl cysteamine substrate
      substitutes led to substantial insights in terms of cyclization activity and
      substrate tolerance of these enzymes. Their use in engineered hybrid NRPSs is an
      interesting but yet only little explored target for approaches to achieve new
      structural diversity and designed products. RESULTS: To study the capability of
      various Te domains to function in hybrid NRPSs, six different Te domains that
      catalyze different modes of termination in their natural systems were fused to a
      bimodular model NRPS system, consisting of the first two modules of tyrocidine
      NRPS, TycA and ProCAT. All Te domains were active in hydrolyzing the
      enzymatically generated dipeptide substrate D-Phe-Abu from the NRPS template
      with, however, greatly varying turnover rates. Two Te domains were also capable
      of hydrolyzing the substrate D-Phe-Pro and partially cyclized the D-Phe-Abu
      dipeptide, indicating that in an artificial context Te domains may display
      hydrolytic and cyclization activities that are not easily predictable.
      CONCLUSIONS: Te domains from heterologous NRPSs can be utilized for the
      construction of hybrid NRPSs. This is the first comparative study to explore
      their influence on the product pattern. The inherent specificity and
      regioselectivity of Te domains should allow control of the desired product
      cleavage, but can also lead to other modes of termination potentially useful for
      generating structural diversity. Our results provide the first data for choosing
      the proper Te domain for a particular termination reaction.

PMID- 11590025
TI  - Could insulin protect against atherosclerosis?

PMID- 11590026
TI  - New antibody therapies for HIV.

PMID- 11590029
TI  - Personalia. Cracking the genomes: J. Craig Venter at his 55th anniversary.

PMID- 11590030
TI  - Steven Holtzman discusses partnering.

PMID- 11590031
TI  - DNA microarray technology and integrative viral genomics.

PMID- 11590032
TI  - Drug discoverers - you need us! - Reply.

PMID- 11590033
TI  - Cholesterol modulation as an emerging strategy for the treatment of Alzheimer's
      disease.
AB  - The basis for therapeutic strategies targeting the amyloid-beta protein (Abeta)
      has come from studies showing that accumulation and aggregation of the Abeta
      within the brain is likely to cause Alzheimer's disease (AD). Along with an ever
      increasing understanding of Abeta metabolism, many potential therapeutic
      strategies aimed at altering Abeta metabolism have emerged. Among the more
      intriguing targets for therapy are enzymes involved in cholesterol homeostasis,
      because it has been found that altering cholesterol can influence Abeta
      metabolism in experimental model systems, and that cholesterol-lowering agents,
      specifically HMG-CoA reductase inhibitors, could reduce the incidence of AD. It
      is likely that cholesterol influences Abeta metabolism in several ways, including
      altering Abeta production and perhaps altering Abeta deposition and clearance.
      Thus, pharmacological modulation of cholesterol levels could provide a relatively
      safe means to reduce Abeta accumulation in the brain, and thereby prevent or slow
      the development of AD.

PMID- 11590034
TI  - Insulin therapies - past, present and future.
AB  - The discovery of insulin is one of the greatest milestones in medical history.
      This discovery revolutionized the use of peptides and proteins as therapeutic
      agents. For more than six decades, insulin from different animal sources was
      used, until the breakthrough in biotechnology made it possible to produce human
      insulin in sufficient amounts. The evolution of the biotechnological era gave
      rise to modified insulins to solve some of the bottlenecks in insulin therapy.
      Efforts are currently focused towards developing non-invasive insulin delivery
      systems, and there are several competing technologies in different stages of
      development. The next few years will see several novel approaches to mimic the
      endogenous release and kinetics of insulin, and also many improved analogues
      designed to achieve better control and effective treatment of diabetes.

PMID- 11590035
TI  - Human disease characterization: real-time quantitative PCR analysis of gene
      expression.
AB  - Real-time quantitative PCR is the measurement of a fluorescent signal generated
      and measured during PCR as a consequence of amplicon synthesis. When used as
      reverse transcriptase-PCR (RT-PCR), real-time quantitative PCR has proved to be
      useful in accurately measuring expression levels of specific gene transcripts.
      When applied to questions of minimal residual disease, the technique has evolved
      from generically detecting the presence of disease cells in individuals, such as
      the AML1-ETO fusion transcript, to the identification of a specific gene, such as
      BCL-6, which is prognostic for determining the therapeutic outcome of patients
      with diffuse large B-cell lymphoma.

PMID- 11590036
TI  - Monitor: molecules and profiles.

PMID- 11590037
TI  - Monitor and Molecules.

PMID- 11590038
TI  - Novel antifungals; Cholesterol-ester transfer-protein-mRNA ligands.

PMID- 11590039
TI  - Monitor and Molecules.

PMID- 11590040
TI  - The long and the short of stomatal density signals.

PMID- 11590041
TI  - Integration of light and brassinosteroid signals in etiolated seedling growth.

PMID- 11590042
TI  - An integrated Arabidopsis annotation database for Affymetrix Genechip data
      analysis, and tools for regulatory motif searches.
AB  - Genome-scale sequencing projects have provided the essential information required
      for the construction of entire genome chips or microarrays for RNA expression
      studies. The Arabidopsis and rice genomes have been sequenced and whole-genome
      oligonucleotide arrays are being manufactured. These should soon become available
      to researchers. Expression studies using genomic-scale expression arrays are
      providing us with a vast quantity of information at a rapid pace. The rate
      limiting step in this type of experiments is not the data generation step but
      rather the data analysis component of experiments. We report improvements that
      should facilitate the analysis of Affymetrix Genechip expression data.

PMID- 11590043
TI  - A distinctive voice for ethylene signaling in hypoxia.

PMID- 11590044
TI  - Studying the historic migrations of the Irish potato famine pathogen using
      ancient DNA.

PMID- 11590045
TI  - Engineering salt tolerance in crop plants.

PMID- 11590046
TI  - Apoptosis: a way of life for plants?

PMID- 11590064
TI  - Seeds for a better future: 'low phytate' grains help to overcome malnutrition and
      reduce pollution.
AB  - myo-Inositol(1,2,3,4,5,6)hexakisphosphate (InsP(6) or 'phytic acid') was first
      known as the storage form of phosphorus in seeds. Seed-derived dietary InsP(6)
      can contribute to iron and zinc deficiency in human populations. Excretion of
      'phytic acid phosphorus' by non-ruminants such as poultry, swine and fish can
      contribute to water pollution. Sustainable solutions to these important problems
      might depend on progress in the molecular biology and genetics of InsP(6)
      accumulation during seed development. The development of 'low phytate' grain and
      legume genotypes could help advance our understanding of this biology, and when
      used in foods and feeds might help to reduce human malnutrition and reduce animal
      waste phosphorus.

PMID- 11590065
TI  - Ubiquitylation in plants: a post-genomic look at a post-translational
      modification.
AB  - In this article, we summarize Arabidopsis genes encoding ubiquitin, ubiquitin
      activating enzyme (E1), ubiquitin-conjugating enzymes (E2s) and an additional
      selected set of proteins related to ubiquitylation. We emphasize comparisons to
      components from Saccharomyces cerevisiae, with occasional reference to animals.
      Among the E1 and E2s, Arabidopsis usually has two to four probable orthologs to
      one yeast gene. Also, Arabidopsis has genes with no likely ortholog in yeast,
      although they often have potential orthologs in animals. The large number of
      components with known function in ubiquitylation indicates that this process
      plays a complex role in cellular physiology.

PMID- 11590066
TI  - Pathways of plastid-to-nucleus signaling.
AB  - Several plastid signals have been identified that regulate the transcription of
      nuclear genes for plastid and non-plastid proteins. These signals are related to
      the photosynthetic metabolism of chloroplasts and include porphyrins, reactive
      oxygen intermediates and carotenoids. The metabolic and developmental state of
      the chloroplast also control cell differentiation and leaf morphogenesis, but the
      signaling pathways have not been characterized. Plastid-to-nucleus and light
      signaling pathways are separable in some but not all cases. Retrograde signaling
      thus plays a central role in coordinating gene expression in the nucleus, plastid
      and mitochondrion, and in integrating pathways of cellular metabolism and
      development.

PMID- 11590067
TI  - Molecular secrets of bacterial type III effector proteins.
AB  - Most Gram-negative phytopathogenic bacteria are thought to inject effector
      proteins into the plant cell via a type III secretion system that is essential
      for pathogenicity. Plant targets and the mode of action of type III effector
      proteins, which include avirulence (Avr) proteins, are largely unknown. However,
      recent findings have shed light on the molecular mechanisms of Avr action. Here,
      we focus on two classes of Avr proteins (the AvrBs3 and AvrRxv/YopJ families)
      that have been suggested to act as transcription factors and proteases,
      respectively.

PMID- 11590068
TI  - The functions of inter- and intracellular glutathione transport systems in
      plants.
AB  - Glutathione is one of the major redox buffers in most aerobic cells, and it has a
      broad spectrum of functions in plants. Recent discoveries implicate this thiol
      peptide in signalling and cellular homeostasis. Glutathione can sense
      intracellular redox status: perturbations of glutathione reduction state are
      transduced into changes in gene expression. This central role demands precise
      control of both the concentration and the reduction state of glutathione in
      different compartments. In addition to the regulation of glutathione biosynthesis
      and redox state, attention is now turning to the role of glutathione
      transporters.

PMID- 11590069
TI  - Future of plant science in Zimbabwe.
AB  - Zimbabwe's agricultural biotechnology research capacity is located at
      universities, government research institutions and parastatal (state funded)
      organizations. Projects range from those using traditional biotechnology to a few
      that are experimenting with genetically modified organisms (GMOs).

PMID- 11590070
TI  - Periodontal disease and periodontal management in patients with cancer.
AB  - Periodontal infection may exacerbate during cancer therapy and may result in oral
      pain and infection, and systemic infection, which may cause morbidity and can
      lead to mortality in neutropenic cancer patients. Periodontal disease in head and
      neck cancer patients treated with radiation therapy may lead to acute and chronic
      complications. The literature was reviewed by a search of Medline of the National
      Library of Medicine. The search was conducted to identify publications assessing
      periodontal disease in cancer patients. In addition, a review of papers
      referenced in the retrieved papers was conducted to identify additional
      publications for review. Periodontal disease should be assessed and managed prior
      to medical treatment of cancer for those with oropharyngeal cancer, and for
      patients in whom neutropenia may develop during treatment. Pretreatment
      assessment and management, and maintenance of oral hygiene have been shown to be
      effective in preventing oral and systemic complications during treatment. A
      complete oral and periodontal examination is appropriate for all patients planned
      to receive head and neck radiation therapy and those to be treated with medical
      protocols that are anticipated to result in neutropenia. Oral and periodontal
      care must continue following cancer therapy, and requires that the health care
      provider have an understanding of the malignant disease, oral manifestations of
      the disease, medical management of the disease, and of the oral complications
      that may develop.

PMID- 11590071
TI  - Loss of MDM2 expression in human head and neck squamous cell carcinomas and
      clinical significance.
AB  - The transforming potential of the MDM2 oncogene has been attributed to the
      overproduction of the protein. In order to investigate regulation of MDM2
      expression in head and neck squamous cell carcinomas, we analysed MDM2 gene
      amplification, and mRNA and protein expression in tumour specimens from 62
      patients, in cell lines, and in normal epithelium adjacent to tumours or obtained
      from healthy patients. Additionally, TP53-induced MDM2-P2 transcription was
      evaluated and compared with TP53 status. MDM2 gene amplification and mRNA over
      expression is infrequent, 7 and 9%, respectively. The predominant transcript
      codes for full-length MDM2 protein (90kD) and the level of alternatively spliced
      forms is not significant. We show that only 47% of tumours exhibit MDM2
      immunostaining in more than one third of the neoplastic cells, and thus more than
      half of the tumours display no or low levels of MDM2 protein. In contrast, MDM2
      protein is always detectable in basal and parabasal cells of morphologically
      normal epithelium outside the invasively growing tumour, as well as in a normal
      uvula sample. Similarly, the total amount of MDM2 transcripts analysed by reverse
      transcriptase-polymerase chain reaction is reduced in tumour samples compared to
      normal tissues, essentially due to a decrease in P2 transcript levels. The
      relationship between mutated p53 status and low levels of MDM2 found in cell
      lines is also observed to a certain extent in primary tumour samples. Overall,
      there is a high frequency of TP53 mutation and under-expression of MDM2 in the
      head and neck tumours. Moreover, a significant association of decreased MDM2
      expression is observed with advanced tumour stage and 3 years survival.

PMID- 11590072
TI  - Oral topical doxepin rinse: analgesic effect in patients with oral mucosal pain
      due to cancer or cancer therapy.
AB  - Oral mucositis is a treatment limiting toxicity of cancer therapy. The purpose of
      this study was to assess the impact of doxepin oral rinse in the management of
      oral mucosal pain in cancer patients. Forty-one cancer patients with oral mucosal
      pain were provided a solution of doxepin (0.5%) for oral rinsing. Oral pain was
      assessed prior to rinsing, and following rinsing for 4 h using a visual analogue
      scale (VAS). Adverse effects were recorded. Doxepin rinse resulted in a reduction
      of pain intensity of more than 50%, with pain relief extending for more than 3 h
      with pain not returning to baseline 4 h after rinsing. The rinse was tolerated by
      patients with mucosal damage, and had acceptable taste, and infrequent mucosal
      stinging with use. Some patients reported sedation after use, likely due to
      systemic absorption. The results of this single dose trial suggest that topical
      doxepin rinse has significant ability to provide clinically significant pain
      relief in patients with mucosal damage with an extended duration of effect.

PMID- 11590073
TI  - Effect of N-CAM on in vitro invasion of human adenoid cystic carcinoma cells.
AB  - Adenoid cystic carcinoma of salivary glands is characterised by aggressive
      behaviour, high rate of local recurrences, neurotropism and late metastasis. In a
      previous work we demonstrated that adenoid cystic carcinoma cultured cells (CAC2
      cells) expressed N-CAM. It was suggested that this expression, modulated by
      extracellular matrix, would be correlated to cell movement. The aim of our study
      was to verify whether CAC2 cells presented invasion capacity. Moreover, we tested
      whether the neural adhesion molecule (N-CAM) would participate in this process.
      CAC2 cells were either previously treated, or not (control), with a monoclonal
      antibody against N-CAM. Invasion assays were carried out using a modified Boyden
      chamber (Transwell chamber). CAC2 cells (10(5)) were dispensed into Transwell
      upper chamber on the top of Matrigel coated filter. The cells that invaded the
      filters in the first 8 h were counted under light microscopy, yielding data for
      the invasion rates (%). Control CAC2 cells presented an invasion rate of 5.28+/
      0.04%. The invasion rate raised to 6.53+/-0.2% when N-CAM was blocked with
      monoclonal antibody. N-CAM impaired the adenoid cystic carcinoma cell invasion in
      vitro. Therefore, we suggest an anti-invasive role for N-CAM in adenoid cystic
      carcinoma.

PMID- 11590074
TI  - Characteristics of antitumour activity of cepharanthin against a human
      adenosquamous cell carcinoma cell line.
AB  - Cepharanthin is one of the biscoclaurine alkaloids widely used for treatment of
      many acute and chronic diseases; snakebite, bronchial asthma, alopecia areata,
      leukopenia during radiation therapy or anticancer treatment. Recently, it has
      been reported that cepharanthin exerts antitumour effects by increasing
      immunological competence of the host or apoptosis-inducing activity. In this
      study, we examined the antitumour effects of cepharanthin against a human
      adenosquamous cell carcinoma cell line (TYS). Treatment of TYS cells with
      cepharanthin (10 approximately 20 microg/ml) resulted in a significant
      suppression of cell growth. Moreover, it was found by the flow cytometry
      analysis, nick end labelling or agarose gel electrophoresis, that G1 arrest and
      DNA fragmentation occurred in cepharanthin-treated cells. In addition, it was
      detected that induction of p21(WAF1) protein and activation of caspase 3 protype,
      which is one of Interleukin-1beta converting enzyme (ICE) family proteases, were
      detected by Western blotting. The TYS tumour-bearing nude mice were treated with
      cepharanthin, which was administered subcutaneously (20 mg/kg/day). The
      cepharanthin treatment results in a significant suppression of tumour growth and
      an induction of apoptosis. These findings suggest that cepharanthin induces G1
      arrest via expression of p21(WAF1) and apoptosis through caspase 3.

PMID- 11590075
TI  - Expression of multidrug resistance-related genes in oral squamous cell
      carcinomas.
AB  - To characterize the multidrug resistance (MDR) phenotype in human oral squamous
      cell carcinomas (OSCCs), the expression levels of four MDR-related genes
      (multidrug resistance, mdr1; multidrug resistance-associated protein, MRP;
      glutathione S-transferase-pi, GST-pi; and DNA topoisomerase II, topoII) were
      analyzed in OSCCs. Fifty-two OSCC tissues and 22 normal oral mucosal tissues were
      involved in this study. The expression of each gene was analyzed with a reverse
      transcription polymerase chain reaction (RT-PCR) method using beta(2)m
      microglobulin (beta(2)m) mRNA as an endogenous control. The mean values of mdr1,
      MRP, GST-pi, and topoII gene expression relative to the beta(2)m gene in OSCC
      tissues were 0.37, 0.75, 0.66, and 1.11; those of normal oral mucosa were 0.40,
      0.27, 0.62, and 0.91, respectively. The averaged expression levels of the MRP and
      topoII gene in OSCC tissues were higher than those of normal oral mucosas
      (P=0.001 and P=0.02, respectively). The expression levels of four MDR-related
      genes in OSCCs were not related with the degree of histologic cell
      differentiation, tumor stage, primary or recurred tumor, or the presence or
      absence of chemotherapy. Linear regression analysis showed a correlation between
      the expression levels of MRP and GST-pi in normal oral mucosas (r=0.596, P=0.003)
      and in OSCCs (r=0.287, P=0.039). The results suggest that MRP expression is
      activated during the tumorigenesis of OSCCs and that this may play a role in de
      novo drug resistance in OSCCs. These results should provide further insight into
      the complex role postulated for MDR-related genes in chemotherapy, carcinogenesis
      and tumor progression.

PMID- 11590076
TI  - Cellular neurothekeoma of the oral mucosa.
AB  - Cellular neurothekeoma is an unusual benign neoplasm which, despite its name, is
      of uncertain origin. This report describes a cellular neurothekeoma of the cheek
      mucosa, the first at this site. The tumour presented in a 29-year-old man as a
      discrete mucosal thickening. Histology showed a generally well circumscribed, but
      unencapsulated, solid tumour which replaced the entire lamina propria and
      permeated between minor salivary glands and bundles of striated muscle in the
      submucosa. There was a sub-epithelial Grenz zone. The tumour was composed of
      nodules of pale, epithelioid cells separated by fascicles of spindle cells, with
      smaller strands and nests superficially. The nuclei were vesicular and, though
      mainly bland, occasionally atypical. The stroma was moderately infiltrated by
      mixed chronic inflammatory cells. Prominent nerves and blood vessels were seen at
      the periphery of the lesion, and neoplastic cells were noted within intact
      striated muscle fascicles. With immunohistochemistry, all the neoplastic cells
      strongly expressed NKI/C3, synaptophysin, neurone-specific enolase and vimentin,
      some expressed smooth muscle actin and PGP 9.5, but all were negative for S100,
      factor XIIIa, CD34, CD56, CD57, CD68, chromogranin A, desmin, epithelial membrane
      antigen and von Willebrand factor. The origin of the lesion is thus speculative.
      It was, however, completely excised and in 12 months there has been no
      recurrence.

PMID- 11590077
TI  - Warty carcinoma of the oral mucosa in an HIV+ patient.
AB  - The authors present the case of a 36-year-old HIV+ male patient with a 1-cm
      diameter papillary exophytic lesion of the right cheek. Microscopic examination
      showed a papillary epithelial neoplasm with invasion of the stroma in the
      peripheral part. Cellular and nuclear atypia were present in the superficial and
      in the deep layers of the neoplasm. An in situ hybridization for human
      papillomavirus (HPV) 6, 11, 16, 18, 31, 35 and 51 was performed. A focal
      positivity only for HPV 16 and 18 was present in koilocytotic cells of the most
      peripheral portion of the lesion. The microscopic definitive diagnosis was warty
      carcinoma of the cheek. No recurrence was observed at a 3-year follow-up.

PMID- 11590078
TI  - Hemangioendothelioma of the mandible in a newborn infant - diagnostic and
      treatment approach of a rare vascular tumor.
AB  - Infantile hemangioendotheliomas are rare vascular tumors with predominant
      involvement of the soft tissues of the extremities. The occurence in the head and
      neck region and in particular intraoral occurence is extremely rare. The tumor is
      believed to be a neoplasm of borderline malignancy. We report a case of a 5
      months old infant presenting with a hemangioendothelioma with extensive bony
      destruction of the mandible. Following surgical resection of the tumor with
      segmental mandibular resection primary mandibular reconstruction was performed
      using a rib graft being a useful compromise solution for primary mandibular
      reconstruction in young infants.

PMID- 11590079
TI  - Benign fibrous histiocytoma (BHF) of the cheek: CD 68-KP1 positivity.
AB  - We present a case of fibrous histiocytoma of the cheek in a 32-year-old male with
      no evidence of any regional invasion or distant metastasis. Pathologic analysis
      and diagnosis of these lesions is often challenging, and usually based on a
      combination of light microscopy and immunohistochemistry. In this study the
      diagnosis was confirmed using immunostaining with the antibody CD 68-KP1 that is
      positive in any lesion containing lysosomal granules or phagolysosomes.

PMID- 11590080
TI  - Limitations of the case-only design for identifying gene-environment
      interactions.
AB  - The case-only design, which requires only diseased subjects, allows for
      estimation of multiplicative interactions between factors known to be independent
      in the study population. The design is being used as an alternative to the case
      control design to study gene-environment interactions. Estimates of gene
      environment interactions have been shown to be very efficient relative to
      estimates obtained with a case-control study under the assumption of independence
      between the genetic and environmental factors. In this paper, the authors explore
      the robustness of this procedure to uncertainty about the independence
      assumption. By using simulations, they demonstrate that inferences about the
      multiplicative interaction with the case-only design can be highly distorted when
      there is departure from the independence assumption. They illustrate their
      results with a recent study of gene-environment interactions and risk of lung
      cancer incidence in a cohort of miners from the Yunnan Tin Corporation in
      southern China. Investigators should be aware that the increased efficiency of
      the case-only design is a consequence of a strong assumption and that this design
      can perform poorly if the assumption is violated.

PMID- 11590081
TI  - Effects of smoking reduction during pregnancy on the birth weight of term
      infants.
AB  - This study was undertaken to determine 1) whether reducing tobacco exposure
      during pregnancy increases the birth weight of term infants and 2) the relative
      effects of early- and late-pregnancy exposure to tobacco on infant birth weight.
      Data were obtained from the Smoking Cessation in Pregnancy project, conducted in
      public clinics in three states (Colorado, Maryland, and Missouri) between 1987
      and 1991. Self-reported cigarette use and urine cotinine concentration were
      collected from 1,583 pregnant smokers at study enrollment and in the third
      trimester. General linear models were used to generate mean adjusted birth
      weights for women who reduced their tobacco exposure by 50 percent or more and
      for those who did not change their exposure. Regression smoothing techniques were
      used to characterize the relation between birth weight and early exposure and
      birth weight and third-trimester exposure. Reducing cigarette use was associated
      with an increase in mean adjusted birth weight of only 32 g, which was not
      significant (p = 0.33). As third-trimester cigarette use increased, birth weight
      declined sharply but leveled off at more than eight cigarettes per day. Findings
      were similar when urine cotinine concentration was used. Women who smoke during
      pregnancy may need to reduce to low levels of exposure (less than eight
      cigarettes per day) to improve infant birth weight.

PMID- 11590082
TI  - Case-cohort analysis of agricultural pesticide applications near maternal
      residence and selected causes of fetal death.
AB  - The potential association between fetal death and residential proximity to
      agricultural pesticide applications was examined in 10 California counties for
      1984. A case-cohort analysis utilized 319 cases of selected causes of fetal death
      other than congenital anomalies and 611 non-cases. A statewide database of all
      applications of restricted pesticides was linked to maternal address; residential
      proximity within 1 mile (1.6 km) provided a surrogate for daily exposure.
      Pesticides were grouped by chemical class and mechanism of acetylcholinesterase
      inhibition. Multivariate proportional hazards models using time-dependent
      exposure variables were fit for each pesticide grouping. Overall, pesticides
      showed no strong association with fetal death. Slightly elevated risks were
      observed for women who resided near applications of halogenated hydrocarbons,
      carbamates, estrogenic pesticides, and carbamate acetylcholinesterase inhibitors
      during the second trimester, with hazard ratios of 1.3 (95% confidence interval
      (CI): 1.0, 1.8), 1.3 (95% CI: 1.0, 1.8), 1.4 (95% CI: 0.8, 2.5), and 1.3 (95% CI:
      1.0, 1.8), respectively. In a month-by-month analysis, elevated risks were
      observed when exposure occurred during gestational months 3 and 4 for carbamates
      and carbamate inhibitors and during months 4 and 5 for halogenated hydrocarbons.
      Since previous studies have relied on personal recall of exposure, major
      strengths of this study were the objective source for environmental pesticide
      exposure assessment and the use of data on the timing of exposure.

PMID- 11590083
TI  - Stability and change in children's intelligence quotient scores: a comparison of
      two socioeconomically disparate communities.
AB  - The authors estimated the influence of familial factors and community
      disadvantage on changes in children's intelligence quotient (IQ) scores from age
      6 years to age 11 years. Data were obtained from a longitudinal study of the
      neuropsychiatric sequelae of low birth weight in two socioeconomically disparate,
      geographically defined communities in the Detroit, Michigan, metropolitan area.
      Representative samples of low birth weight and normal birth weight children from
      the City of Detroit (urban) and nearby middle-class suburbs (suburban) were
      assessed at age 6 years (in 1990-1992) and age 11 years (in 1995-1997) (n = 717).
      Children's IQs were measured using the Wechsler Intelligence Scale for Children
      Revised. The familial factors considered included maternal IQ, education, and
      marital status. Multiple regression analysis applying generalized estimating
      equations was used. The IQs of urban children, regardless of birth weight,
      declined from age 6 years to age 11 years. The downward shift increased by 50%
      the proportion of urban children scoring 1 standard deviation below the
      standardized IQ mean of 100. A negligible change was observed in suburban
      children. Maternal IQ, education, and marital status and low birth weight
      predicted IQ at age 6 years but were unrelated to IQ change. Growing up in a
      racially segregated and disadvantaged community, more than individual and
      familial factors, may contribute to a decline in IQ score in the early school
      years.

PMID- 11590084
TI  - Effects of race, cigarette smoking, and use of contraceptive medications on
      resting energy expenditure in young women.
AB  - The prevalence of obesity is higher in Black women than in White women (JAMA
      1994;272:205-11; Arch Pediatr Adolesc Med 1995;149:1085-91). Although it has been
      shown that Black women have a lower resting energy expenditure (REE), factors
      affecting REE remain unclear. This 1996-1997 study in Cincinnati, Ohio, assessed
      racial differences in REE and their determinants in a biracial cohort of 152
      healthy young women aged 18-21 years. Two indirect calorimetric measurements were
      obtained during two overnight hospital admissions 10-14 days apart. Body
      composition was measured by using dual-energy x-ray absorptiometry. Mean REE
      (adjusted for body composition, smoking, and contraceptive medication use) was
      significantly (p = 0.04) lower by 71 kcal/day in Black women (1,453 (standard
      error, 21) kcal/day) than in White women (1,524 (standard error, 19) kcal/day).
      Smoking was associated with a REE that was 68 kcal/day higher for both groups (p
      = 0.03). A trend (p = 0.07) toward increased REE (by 46 kcal/day) was found with
      contraceptive medication use. In conclusion, young Black women had a
      significantly lower REE than did White women. Cigarette smoking significantly
      increased REE. The apparent presence of a more parsimonious energy metabolism in
      Black women suggests that maintenance of energy homeostasis requires particular
      vigilance in this high-risk population.

PMID- 11590085
TI  - Proximate and contextual socioeconomic determinants of mortality: multilevel
      approaches in a setting with universal health care coverage.
AB  - Investigations of contextual factors (income inequality, cultural disruption,
      access to health and social services, safety and crime rate, and others) have
      received little emphasis by epidemiologists, although a few have demonstrated the
      importance of such factors for mortality, particularly in the United States. To
      expand current understanding of the importance of contextual factors, the authors
      evaluated mortality in a longitudinal study in Nova Scotia, Canada, where all
      residents have greater access to health and social services and where income
      inequalities are smaller than in the United States. A total of 2,116 participants
      were followed from 1990 through December 1999, linked to the 1991 Canada Census
      as a source of neighborhood characteristics, and analyzed using individual-level
      and multilevel logistic regression. Well-educated and high-earning persons fared
      better. Neighborhood socioeconomic characteristics (neighborhood income,
      educational level, unemployment rate), in contrast, were not significantly
      associated with mortality. However, within advantaged neighborhoods, the
      importance of individual income and education for mortality was increased
      relative to disadvantaged neighborhoods. The latter findings may direct health
      policy aimed at reducing health inequalities.

PMID- 11590086
TI  - Prospective assessment of estrogen replacement therapy and cognitive functioning:
      atherosclerosis risk in communities study.
AB  - Studies of humans have not confirmed the suggestion from animal studies that
      estrogen replacement therapy may have an inverse relation with cognitive function
      decline. Because many of these studies have been marred by design or
      methodological problems, such as a small sample size, failure to control for
      confounding variables, or the use of a cross-sectional design, the present study
      was conducted in a large cohort of middle-aged postmenopausal women participating
      in the Atherosclerosis Risk in Communities (ARIC) Study. The study population
      consisted of 2,859 women aged 48-67 years, whose cognitive function was tested at
      the second (1990-1992) and fourth (1996-1998) visits of the ARIC Study using
      three instruments: the Delayed Word Recall Test, Digit Symbol Subtest of the
      Wechsler Adult Intelligence Scale-Revised, and Word Fluency Test. After multiple
      adjustment, no consistent patterns of cognitive changes between the two cohort
      visits could be detected according to current use or duration of use of estrogen
      replacement therapy. Thus, the results of the present study do not support the
      hypothesis that estrogen replacement therapy may slow age-related cognitive
      decline, at least as it applies to relatively young postmenopausal women.

PMID- 11590087
TI  - Exploring the relation of alcohol consumption to risk of breast cancer.
AB  - There are lingering questions regarding the relation between alcohol consumption
      and breast cancer risk in women. The authors performed a meta-analysis of
      epidemiologic studies carried out through 1999 to examine the dose-response
      relation and to assess whether effect estimates differed according to various
      study characteristics. Overall, there was a monotonic increase in the relative
      risk of breast cancer with alcohol consumption, but the magnitude of the effect
      was small; in comparison with nondrinkers, women averaging 12 g/day of alcohol
      consumption (approximately one typical drink) had a relative risk of 1.10 (95%
      confidence interval (CI): 1.06, 1.14). Estimates of relative risk were 7% greater
      in hospital-based case-control studies than in cohort studies or community-based
      case-control studies, 3% greater in studies published before 1990 than in studies
      published later, and 5% greater in studies conducted outside of the United States
      than in US studies. The findings of five US cohort studies published since 1990
      yielded a relative risk of 1.06 (95% CI: 1.00, 1.11) for consumers of 12 g/day,
      as compared with nondrinkers. Cohort studies with less than 10 years of follow-up
      gave estimates 11% higher than cohort studies with longer follow-up periods. No
      meaningful difference was seen by menopausal status or type of beverage consumed.

PMID- 11590088
TI  - Alcohol consumption and the risk of type 2 diabetes mellitus: atherosclerosis
      risk in communities study.
AB  - Evidence regarding the association between alcohol consumption and type 2
      diabetes risk remains inconsistent, particularly with regard to male-female
      differences. The authors conducted a prospective study of type 2 diabetes risk
      associated with alcohol consumption in a cohort of 12,261 middle-aged
      participants of the Atherosclerosis Risk in Communities Study (1990-1998), who
      were followed between 3 and 6 years. Alcohol consumption at baseline was
      characterized into lifetime abstainers, former drinkers, and current drinkers of
      various levels. Incident diabetes was determined by blood glucose measurements
      and self-report. After adjustment for potential confounders, an increased risk of
      diabetes was found in men who drank >21 drinks/week when compared with men who
      drank < or =1 drink/week (odds ratio = 1.50, 95% confidence interval: 1.02, 2.20)
      while no significant association was found in women. This increased diabetes risk
      among men who drank >21 drinks/week was predominantly related to spirits rather
      than to beer or wine consumption. The relative odds of incident diabetes in a
      comparison of men who drank >14 drinks of spirits per week with men who were
      current drinkers but reported no regular use of spirits, beer, or wine were 1.82
      (95% confidence interval: 1.14, 2.92). Results of this study support the
      hypothesis that high alcohol intake increases diabetes risk among middle-aged
      men. However, more moderate levels of alcohol consumption do not increase risk of
      type 2 diabetes in either middle-aged men or women.

PMID- 11590089
TI  - White blood cell count and incidence of coronary heart disease and ischemic
      stroke and mortality from cardiovascular disease in African-American and White
      men and women: atherosclerosis risk in communities study.
AB  - The authors examined the association between white blood cell (WBC) count and
      incidence of coronary heart disease and ischemic stroke and mortality from
      cardiovascular disease in 13,555 African-American and White men and women from
      the Atherosclerosis Risk in Communities (ARIC) Study. Blood was drawn at the ARIC
      baseline examination, beginning in 1987-1989. During an average of 8 years of
      follow-up (through December 1996), there were 488 incident coronary heart disease
      events, 220 incident strokes, and 258 deaths from cardiovascular disease. After
      adjustment for age, sex, ARIC field center, and multiple risk factors, there was
      a direct association between WBC count and incidence of coronary heart disease (p
      < 0.001 for trend) and stroke (p for trend < 0.001) and mortality from
      cardiovascular disease (p for trend < 0.001) in African Americans. The African
      Americans in the highest quartile of WBC count (> or =7,000 cells/mm(3)) had 1.9
      times the risk of incident coronary heart disease (95% confidence interval (CI):
      1.19, 3.09), 1.9 times the risk of incident ischemic stroke (95% CI: 1.03, 3.34),
      and 2.3 times the risk of cardiovascular disease mortality (95% CI: 1.38, 3.72)
      as their counterparts in the lowest quartile of WBC count (<4,800 cells/mm(3)).
      These associations were similar in Whites and in never smokers. An elevated WBC
      count is directly associated with increased incidence of coronary heart disease
      and ischemic stroke and mortality from cardiovascular disease in African-American
      and White men and women.

PMID- 11590091
TI  - Binge drinking in pregnancy--frequency and methodology.
AB  - Independent of average alcohol intake, the effect of binge drinking on adverse
      pregnancy outcomes in humans is only sporadically reported, but most studies in
      humans have found little or no effect of binge drinking on several adverse
      pregnancy outcomes. In a representative sample of 371 pregnant Danish women, the
      agreement between two different measures of binge drinking during the first half
      of pregnancy obtained from interviews and questionnaires was assessed, and the
      frequency and pattern of binge drinking were described. The percentage of
      agreement between the methods ranged between 81% and 86%. The proportion of women
      who reported binge drinking depended on the definition of pregnancy, but the
      proportion peaked in week 3 measured from the last menstrual period and
      thereafter declined to approximately 1 percent in week 7. On the basis of this
      1998 study, it is suggested that most human studies on binge drinking in
      pregnancy may have failed to find any association because of methodological
      problems. It is suggested that future studies should take into account the number
      of binge episodes as well as the time of binge drinking. This information may
      easily be obtained from most pregnant women by asking two questions in interviews
      or questionnaires.

PMID- 11590090
TI  - Modeling preclinical cardiovascular risk for use in epidemiologic studies: Miami
      community health study.
AB  - To develop a method for assessing preclinical cardiovascular disease risk, models
      of resting cardiovascular regulation and of insulin metabolic syndrome were
      derived from information collected from 1991 to 1996 in a culturally
      heterogeneous sample of 319 healthy men and women (aged 25-44 years) from Miami
      Dade County, Florida. The model of resting cardiovascular regulation used 8
      noninvasive measures of autonomic and cardiovascular function. Three factors were
      derived: 1) parasympathetic, 2) inotropy, and 3) systemic vascular resistance.
      The model of insulin metabolic syndrome used 12 measures assessing body mass,
      insulin, glucose, and lipid metabolism. Four factors were derived: 1) body mass
      and fat distribution, 2) glucose level and regulation, 3) insulin level and
      regulation, and 4) plasma lipid levels. Analyses of the association of the two
      models revealed that subjects with lower cardiac contractility had greater body
      mass, higher fasting and postload insulin and glucose levels, and lower insulin
      sensitivity. Subjects with greater vascular resistance had greater body mass,
      higher total cholesterol and triglyceride levels, and lower high density
      lipoprotein cholesterol levels. These findings indicate that preclinical
      cardiovascular disease risk may involve pathophysiologic processes in which
      cardiac inotropic and vasodilatory functions are linked to specific aspects of
      insulin metabolic syndrome.

PMID- 11590092
TI  - Re: "Lung cancer among industrial sand workers exposed to crystalline silica".

PMID- 11590093
TI  - Training for bioinformatics and computational biology.

PMID- 11590094
TI  - Principal component analysis for clustering gene expression data.
AB  - MOTIVATION: There is a great need to develop analytical methodology to analyze
      and to exploit the information contained in gene expression data. Because of the
      large number of genes and the complexity of biological networks, clustering is a
      useful exploratory technique for analysis of gene expression data. Other
      classical techniques, such as principal component analysis (PCA), have also been
      applied to analyze gene expression data. Using different data analysis techniques
      and different clustering algorithms to analyze the same data set can lead to very
      different conclusions. Our goal is to study the effectiveness of principal
      components (PCs) in capturing cluster structure. Specifically, using both real
      and synthetic gene expression data sets, we compared the quality of clusters
      obtained from the original data to the quality of clusters obtained after
      projecting onto subsets of the principal component axes. RESULTS: Our empirical
      study showed that clustering with the PCs instead of the original variables does
      not necessarily improve, and often degrades, cluster quality. In particular, the
      first few PCs (which contain most of the variation in the data) do not
      necessarily capture most of the cluster structure. We also showed that clustering
      with PCs has different impact on different algorithms and different similarity
      metrics. Overall, we would not recommend PCA before clustering except in special
      circumstances.

PMID- 11590095
TI  - A non-parametric approach to translating gene region heterogeneity associated
      with phenotype into location heterogeneity.
AB  - MOTIVATION: The analysis of genetic data poses statistical problems in the form
      of high dimensionality with small sample sizes. The construction of a composite
      gene region (sequence pair) heterogeneity measure is one technique for reducing
      the dimensionality of the problem. This approach however is not without cost,
      since the contribution of locations to observed gene region differences between
      groups becomes entangled in this summary measure. This is problematic since it is
      of scientific interest to identify locations that together depict phenotype.
      RESULTS: A method is proposed for relating observed gene region heterogeneity
      back to the location level. In the spirit of a factor analysis-type setting, the
      approach focuses on identifying a latent variable structure among locations to
      explain within and between group genetic differences associated with phenotype.
      The method is flexible for identifying either the additive contribution from
      individual locations or the additive contribution from a group of locations, to
      observed gene region heterogeneity, depending upon the weighting scheme used in
      constructing a gene region heterogeneity measure. The approach is illustrated
      with clinical trial data, where the problem of altered HIV drug susceptibility is
      examined through characterizing location contributions to HIV protease gene
      region differences associated with a phenotypic treatment response. AVAILABILITY:
      The Splus (MathSoft, Inc. S-Plus 2000, Seattle, WA, 1999) developed menu-driven
      functions for obtaining results, GENE_ S (J.Kowalski, Harvard School of Public
      Health, Boston, MA 2001), is available from the author upon request.

PMID- 11590096
TI  - Comprehensive comparison between locations of orthologous genes on archaeal and
      bacterial genomes.
AB  - MOTIVATION: Following an extensive search for orthologous genes between the
      complete genomes from archaea and bacteria, the spatial association of the
      orthologs has been investigated in terms of synteny, the conservation of the
      order of neighboring genes. However, the relationships between the relative
      locations of remote orthologs over entire genomes have not been shown. RESULTS:
      Comprehensive comparisons between the locations of orthologs on nineteen archaeal
      and bacterial genomes are presented by the location to location correspondence
      based on the gene-location distance. When the two genomes are rotated such that a
      pair of orthologs with the shortest distance is set in the same angle, a
      statistically significant number of orthologs maintain their relative locations
      between the genomes. Even by the short distances at the 5% significance level,
      the rotations are restricted within a narrow range, suggesting an intrinsic angle
      for realizing similar locations between the orthologs in each genome pair.
      Furthermore, the rotations in the restricted range agree with the replication
      origin and terminus sites for the analyzed genomes where such sites are known.
      The relationship between location-maintained orthologs and gene function is also
      discussed.

PMID- 11590097
TI  - Evolutionary HMMs: a Bayesian approach to multiple alignment.
AB  - MOTIVATION: We review proposed syntheses of probabilistic sequence alignment,
      profiling and phylogeny. We develop a multiple alignment algorithm for Bayesian
      inference in the links model proposed by Thorne et al. (1991, J. Mol. Evol., 33,
      114-124). The algorithm, described in detail in Section 3, samples from and/or
      maximizes the posterior distribution over multiple alignments for any number of
      DNA or protein sequences, conditioned on a phylogenetic tree. The individual
      sampling and maximization steps of the algorithm require no more computational
      resources than pairwise alignment. METHODS: We present a software implementation
      (Handel) of our algorithm and report test results on (i) simulated data sets and
      (ii) the structurally informed protein alignments of BAliBASE (Thompson et al.,
      1999, Nucleic Acids Res., 27, 2682-2690). RESULTS: We find that the mean sum-of
      pairs score (a measure of residue-pair correspondence) for the BAliBASE
      alignments is only 13% lower for Handelthan for CLUSTALW(Thompson et al., 1994,
      Nucleic Acids Res., 22, 4673-4680), despite the relative simplicity of the links
      model (CLUSTALW uses affine gap scores and increased penalties for indels in
      hydrophobic regions). With reference to these benchmarks, we discuss potential
      improvements to the links model and implications for Bayesian multiple alignment
      and phylogenetic profiling. AVAILABILITY: The source code to Handelis freely
      distributed on the Internet at http://www.biowiki.org/Handel under the terms of
      the GNU Public License (GPL, 2000, http://www.fsf.org./copyleft/gpl.html).

PMID- 11590098
TI  - A simple algorithm to infer gene duplication and speciation events on a gene
      tree.
AB  - MOTIVATION: When analyzing protein sequences using sequence similarity searches,
      orthologous sequences (that diverged by speciation) are more reliable predictors
      of a new protein's function than paralogous sequences (that diverged by gene
      duplication), because duplication enables functional diversification. The utility
      of phylogenetic information in high-throughput genome annotation
      ('phylogenomics') is widely recognized, but existing approaches are either manual
      or indirect (e.g. not based on phylogenetic trees). Our goal is to automate
      phylogenomics using explicit phylogenetic inference. A necessary component is an
      algorithm to infer speciation and duplication events in a given gene tree.
      RESULTS: We give an algorithm to infer speciation and duplication events on a
      gene tree by comparison to a trusted species tree. This algorithm has a worst
      case running time of O(n(2)) which is inferior to two previous algorithms that
      are approximately O(n) for a gene tree of sequences. However, our algorithm is
      extremely simple, and its asymptotic worst case behavior is only realized on
      pathological data sets. We show empirically, using 1750 gene trees constructed
      from the Pfam protein family database, that it appears to be a practical (and
      often superior) algorithm for analyzing real gene trees. AVAILABILITY:
      http://www.genetics.wustl.edu/eddy/forester.

PMID- 11590099
TI  - Knowledge representation of signal transduction pathways.
AB  - MOTIVATIONS: Signal transduction is the common term used to define a diverse
      topic that encompasses a large body of knowledge about the biochemical
      mechanisms. Since most of the knowledge of signal transduction resides in
      scientific articles and is represented by texts in natural language or by
      diagrams, there is the need of a knowledge representation model for signal
      transduction pathways that can be as readily processed by a computer as it is
      easily understood by humans. RESULTS: A signal transduction pathway
      representation model is presented. It is based on a compound graph structure and
      is designed to handle the diversity and hierarchical structure of pathways. A
      prototype knowledge base was implemented on a deductive database and a number of
      biological queries are demonstrated on it.

PMID- 11590100
TI  - PIRA PCR designer for restriction analysis of single nucleotide polymorphisms.
AB  - Primer-introduced restriction analysis (PIRA-PCR) is widely used to detect Single
      Nucleotide Polymorphisms (SNPs). To create artificial Restriction Fragment Length
      Polymorphism (RFLP), a mismatch is usually introduced near the end of the primer
      that is close to the mutation of interest. We describe in this report a www-based
      computer program that screens for the suitable mismatches, designs the primers,
      lists the appropriate restriction enzymes and other related information.
      AVAILABILITY: The computer program, with related descriptions, is available at
      http://cedar.genetics.soton.ac.uk/public_html/primer2.html.

PMID- 11590101
TI  - Detecting the impact of sequencing errors on SAGE data.
AB  - SAGE data are obtained by sequencing short DNA tags. Due to the mistakes in DNA
      sequencing, SAGE data contain errors. We propose a new approach to identify tags
      whose abundance is biased by sequencing errors. This approach is based on a
      concept of neighbourhood: abundant tags can contaminate tags whose sequence is
      very close. The application of our approach reveals that moderately abundant tags
      can be generated by sequencing errors uniquely. It also allows for detecting
      correct rare tags. AVAILABILITY: Software is available only to non-profit
      entities and for non-commercial purposes upon request.

PMID- 11590102
TI  - GeneMachine: gene prediction and sequence annotation.
AB  - MOTIVATION: A number of free-standing programs have been developed in order to
      help researchers find potential coding regions and deduce gene structure for long
      stretches of what is essentially 'anonymous DNA'. As these programs apply
      inherently different criteria to the question of what is and is not a coding
      region, multiple algorithms should be used in the course of positional cloning
      and positional candidate projects to assure that all potential coding regions
      within a previously-identified critical region are identified. RESULTS: We have
      developed a gene identification tool called GeneMachine which allows users to
      query multiple exon and gene prediction programs in an automated fashion. BLAST
      searches are also performed in order to see whether a previously-characterized
      coding region corresponds to a region in the query sequence. A suite of Perl
      programs and modules are used to run MZEF, GENSCAN, GRAIL 2, FGENES,
      RepeatMasker, Sputnik, and BLAST. The results of these runs are then parsed and
      written into ASN.1 format. Output files can be opened using NCBI Sequin, in
      essence using Sequin as both a workbench and as a graphical viewer. The main
      feature of GeneMachine is that the process is fully automated; the user is only
      required to launch GeneMachine and then open the resulting file with Sequin.
      Annotations can then be made to these results prior to submission to GenBank,
      thereby increasing the intrinsic value of these data. AVAILABILITY: GeneMachine
      is freely-available for download at http://genome.nhgri.nih.gov/genemachine. A
      public Web interface to the GeneMachine server for academic and not-for-profit
      users is available at http://genemachine.nhgri.nih.gov. The Web supplement to
      this paper may be found at http://genome.nhgri.nih.gov/genemachine/supplement/.

PMID- 11590103
TI  - CHROMA: consensus-based colouring of multiple alignments for publication.
AB  - CHROMA annotates multiple protein sequence alignments by consensus to produce
      formatted and coloured text suitable for incorporation into other documents for
      publication. The package is designed to be flexible and reliable, and has a
      simple-to-use graphical user interface running under Microsoft Windows. Both the
      executables and source code for CHROMA running under Windows and Linux (portable
      command-line only) are freely available at http://www.lg.ndirect.co.uk/chroma.
      Software enquiries should be directed to CHROMA@lg.ndirect.co.uk.

PMID- 11590104
TI  - InterProScan--an integration platform for the signature-recognition methods in
      InterPro.
AB  - InterProScan is a tool that scans given protein sequences against the protein
      signatures of the InterPro member databases, currently--PROSITE, PRINTS, Pfam,
      ProDom and SMART. The number of signature databases and their associated scanning
      tools as well as the further refinement procedures make the problem complex.
      InterProScan is designed to be a scalable and extensible system with a robust
      internal architecture. AVAILABILITY: The Perl-based InterProScan implementation
      is available from the EBI ftp server
      (ftp://ftp.ebi.ac.uk/pub/software/unix/iprscan/) and the SRS-basedInterProScan is
      available upon request. We provide the public web interface
      (http://www.ebi.ac.uk/interpro/scan.html) as well as email submission server
      (interproscan@ebi.ac.uk).

PMID- 11590105
TI  - The HMMTOP transmembrane topology prediction server.
AB  - The HMMTOP transmembrane topology prediction server predicts both the
      localization of helical transmembrane segments and the topology of transmembrane
      proteins. Recently, several improvements have been introduced to the original
      method. Now, the user is allowed to submit additional information about segment
      localization to enhance the prediction power. This option improves the prediction
      accuracy as well as helps the interpretation of experimental results, i.e. in
      epitope insertion experiments. AVAILABILITY: HMMTOP 2.0 is freely available to
      non-commercial users at http://www.enzim.hu/hmmtop. Source code is also available
      upon request to academic users.

PMID- 11590106
TI  - VISTRAJ: exploring protein conformational space.
AB  - VISTRAJ is an application which allows 3D visualization, manipulation and editing
      of protein conformational space using probabilistic maps of this space called
      'trajectory distributions'. Trajectory distributions serve as input to FOLDTRAJ
      which samples protein structures based on the represented conformational space.
      VISTRAJ also allows FOLDTRAJ to be used as a tool for homology model creation,
      and structures may be generated containing post-translationally modified amino
      acids. AVAILABILITY: Binaries are freely available for non-profit use as part of
      the FOLDTRAJ package at ftp://ftp.mshri.on.ca/pub/TraDES/foldtraj/.

PMID- 11590107
TI  - BioLayout--an automatic graph layout algorithm for similarity visualization.
AB  - Graph layout is extensively used in the field of mathematics and computer
      science, however these ideas and methods have not been extended in a general
      fashion to the construction of graphs for biological data. To this end, we have
      implemented a version of the Fruchterman Rheingold graph layout algorithm,
      extensively modified for the purpose of similarity analysis in biology. This
      algorithm rapidly and effectively generates clear two (2D) or three-dimensional
      (3D) graphs representing similarity relationships such as protein sequence
      similarity. The implementation of the algorithm is general and applicable to most
      types of similarity information for biological data. AVAILABILITY: BioLayout is
      available for most UNIX platforms at the following web-site:
      http://www.ebi.ac.uk/research/cgg/services/layout.

PMID- 11590108
TI  - BioWAP, mobile Internet service for bioinformatics.
AB  - We have developed a new Internet service, which provides mobile access to
      bioinformatics databases and software tools. The BioWAP service facilitates
      access to basic bioinformatics databases and analysis tools from everywhere
      without a PC or a laptop computer. Both open source bioinformatics program suites
      and Internet services, which are not designed for mobile Internet access, were
      utilized in the BioWAP service. AVAILABILITY: The BioWAP service starting page
      can be browsed with any WAP terminal from http://bioinf.uta.fi/wml/welcome.wml.

PMID- 11590109
TI  - Critical assessment of microarray data analysis: the 2001 challenge.
AB  - We initiated the Critical Assessment of Microarray Data Analysis (CAMDA)
      conference to stimulate and evaluate the development of advanced data analysis
      techniques for microarrays. A standard data set has been released for this data
      analysis challenge. The goal of this challenge is to assess the performance of
      different analytical methods and at the same time to determine how such methods
      should be evaluated. We hope this effort will catalyze the discussion of
      microarray data analysis among the research community of biologists,
      statisticians, mathematicians, and computer scientists. AVAILABILITY:
      http://camda.duke.edu.

PMID- 11590110
TI  - Dissociation of verbal working memory system components using a delayed serial
      recall task.
AB  - Functional magnetic resonance imaging (fMRI) was used to investigate the neural
      substrates of component processes in verbal working memory. Based on behavioral
      research using manipulations of verbal stimulus type to dissociate storage,
      rehearsal, and executive components of verbal working memory, we designed a
      delayed serial recall task requiring subjects to encode, maintain, and overtly
      recall sets of verbal items for which phonological similarity, articulatory
      length, and lexical status were manipulated. By using a task with temporally
      extended trials, we were able to exploit the temporal resolution afforded by fMRI
      to partially isolate neural contributions to encoding, maintenance, and retrieval
      stages of task performance. Several regions commonly associated with maintenance,
      including supplementary motor, premotor, and inferior frontal areas, were found
      to be active across all three trial stages. Additionally, we found that left
      inferior frontal and supplementary motor regions showed patterns of stimulus and
      temporal sensitivity implicating them in distinct aspects of articulatory
      rehearsal, while no regions showed a pattern of sensitivity consistent with a
      role in phonological storage. Regional modulation by task difficulty was further
      investigated as a measure of executive processing. We interpret our findings as
      they relate to notions about the cognitive architecture underlying verbal working
      memory performance.

PMID- 11590111
TI  - Differential effects of 6-OHDA lesions of the frontal cortex and caudate nucleus
      on the ability to acquire an attentional set.
AB  - Evidence from both human and animal studies indicates that catecholamine
      (dopamine and noradrenaline) imbalances in the fronto-striatal circuitry are
      associated with deficits in higher- order cognitive functions. The present study
      examined how catecholamines within this circuitry modulate attentional function,
      specifically the ability to develop, maintain, and shift an attentional set.
      Catecholamine depletions within the frontal cortex of the common marmoset
      impaired the ability to acquire an attentional set, and increased susceptibility
      to distraction from task-irrelevant stimuli. Analysis of set-shifting performance
      with stimulus dimensions of varying salience suggested that frontal catecholamine
      depletion selectively disrupts "top-down", but not "bottom-up" attentional
      processing. In contrast, the ability to acquire and shift an attentional set
      remained intact following dopaminergic depletion from the caudate nucleus.
      However, the reduced susceptibility to distraction from task-irrelevant stimuli
      displayed by monkeys with dopaminergic depletions of the caudate nucleus suggests
      that responding was under more rigid control by the currently rewarded stimulus.
      The results demonstrate opposite behavioural effects of 6-hydroxydopamine (6
      OHDA) lesions in the frontal cortex and caudate nucleus in tasks requiring
      selective attention. Frontal catecholamine depletion caused an increase in
      distractibility while caudate dopamine loss induced greater focusing of
      responding.

PMID- 11590112
TI  - Pre- and post-mitotic events contribute to the progressive acquisition of area
      specific connectional fate in the neocortex.
AB  - The adult primary motor cortex (area 6) is characterized by a stronger projection
      to the spinal cord than the primary somatosensory cortex (area 3). Here we have
      explored the progressive and regressive phenomena that determine these areal
      differences in the number of corticospinal neurons (CSNs). CSNs were birthdated
      with [(3)H]thymidine and subsequently retrogradely labeled from the spinal cord.
      The time window of CSN production is identical in both areas. The probability
      that a cohort of neuroblasts project to the spinal cord is indicated by the
      percentage of [(3)H]thymidine-positive neurons that can be back-labeled from the
      spinal cord. In the neonate this fate index is significantly higher in area 6
      compared with area 3, indicating that early regionalization of cell fate
      contributes to areal differences in CSN number. In neonatal reeler mice, an
      increase in CSN number was accompanied by an increased fate index, showing that
      the integrity of the post-mitotic environment is required for the specification
      of the appropriate number of neurons expressing a given connectional phenotype.
      Postnatal development in reeler and normal is characterized by an area-specific
      elimination of CSN axons, which reduces areal differences in CSN number. These
      results show a progressive acquisition of CSN fate in the neocortex and indicate
      that both early regionalization and late environmental signals contribute to
      determining areal differences of connectional phenotype.

PMID- 11590113
TI  - Anterior prefrontal cortex mediates rule learning in humans.
AB  - Despite a need for rule learning in everyday life, the brain regions involved in
      explicit rule induction remain undetermined. Here we use event-related functional
      magnetic resonance imaging to measure learning-dependent neuronal responses
      during an explicit categorization task. Subjects made category decisions, with
      feedback, to exemplar letter strings for which the rule governing category
      membership was periodically changed. Bilateral fronto-polar prefrontal cortices
      were selectively engaged following rule change. This activation pattern declined
      with improving task performance reflecting rule acquisition. The vocabulary of
      letters comprising the exemplars was also periodically changed, independently of
      rule changes. This exemplar change modulated activation in left anterior
      hippocampus. Our finding that fronto-polar cortex mediates rule learning supports
      a functional contribution of this region to generic reasoning and problem-solving
      behaviours.

PMID- 11590114
TI  - Effects of domain-specific interference on brain activation associated with
      verbal working memory task performance.
AB  - Previous neuroimaging studies have identified brain regions that underlie verbal
      working memory in humans. According to these studies a phonological store is
      located in the left inferior parietal cortex, and a complementary subvocal
      rehearsal mechanism is implemented by mostly left-hemispheric speech areas. In
      the present functional magnetic resonance imaging study, classical interfering
      and non-interfering dual-task situations were used to investigate further the
      neural correlates of verbal working memory. Verbal working memory performance
      under non-interfering conditions activated Broca's area, the left premotor
      cortex, the cortex along the left intraparietal sulcus and the right cerebellum,
      thus replicating the results from previous studies. By contrast, no significant
      memory- related activation was found in these areas when silent articulatory
      suppression prevented the subjects from rehearsal. Instead, this non-articulatory
      maintenance of phonological information was associated with enhanced activity in
      several other, particularly anterior prefrontal and inferior parietal, brain
      areas. These results suggest that phonological storage may be a function of a
      complex prefronto-parietal network, and not localized in only one, parietal brain
      region. Further possible implications for the functional organization of human
      working memory are discussed.

PMID- 11590115
TI  - Metabolic alterations in the prefrontal and cingulate cortices are related to
      behavioral deficits in a rodent model of attention-deficit hyperactivity
      disorder.
AB  - Rats with a deficit in selective attention accompanied by impulsivity can be
      identified using a five-choice serial reaction time task (5-CSRT) and have been
      proposed to represent a rodent model of attention-deficit hyperactivity disorder
      (ADHD). The aim of the present study was to investigate which brain areas are
      important for visuospatial attention and to test the specific hypothesis that
      dysfunction of the frontal cortex is related to the behavioral deficits observed
      in poorly performing rats. Therefore, [(14)C]deoxyglucose (DG) uptake, an index
      of brain metabolic activity, was measured during the performance of a 5-CSRT task
      in two populations of rats (poorly and well-performing rats) to study the
      relationships between the regional brain activity and behavioral output. While
      performing a 5-CSRT task, poorly performing rats exhibited lower DG uptake in the
      cingulate and ventrolateral orbital cortices than did well-performing rats,.
      Moreover, there was a positive correlation between choice accuracy and DG uptake
      in several areas, especially in the frontal and parietal regions, whereas there
      was an inverse correlation between the percentage of premature responses and DG
      uptake in the ventrolateral orbital and cingulate cortices. These results, which
      demonstrated that the poorly performing rats exhibited metabolic dysfunction in
      the cingulate and prefrontal cortices, provide a basis for the face validity of
      the rodent model of ADHD. Moreover, they suggest that the neural network of
      attention in rats is remarkably analogous to that described in primates.

PMID- 11590116
TI  - Projections from the lateral, basal and accessory basal nuclei of the amygdala to
      the perirhinal and postrhinal cortices in rat.
AB  - The projections from the amygdaloid complex to the hippocampus and surrounding
      cortex have a critical role in the formation of memories for emotionally arousing
      stimuli and in the spread of epileptic seizures. The present study investigated
      the organization of amygdaloid projections to the perirhinal and postrhinal
      cortices by injecting the anterograde tracer Phaseolus vulgaris leucoagglutinin
      into the different subdivisions of the lateral, basal or accessory basal nuclei
      of the amygdala in rat (n = 53). Analysis of immunohistochemically stained
      sections indicated that the medial and dorsolateral divisions of the lateral
      nucleus project heavily to layers I-V of caudal area 35 and to layers I-III of
      the rostroventral postrhinal cortex. The dorsolateral division also moderately
      innervates layer I of caudoventral area 36. The magnocellular division of the
      basal nucleus projects moderately to layers V and VI of rostral areas 35 and 36.
      The parvicellular division of the accessory basal nucleus projects moderately to
      layer V of caudal area 35, whereas the magnocellular division projects moderately
      to layers I and II of rostral area 35. Via these substantial, topographically
      organized projections, the amygdaloid complex might modulate information
      processing at different levels of the medial temporal lobe memory system.

PMID- 11590117
TI  - Visual mechanisms of spatial disorientation in Alzheimer's disease.
AB  - Impaired optic flow perception may contribute to the visuospatial disorientation
      of Alzheimer's disease (AD). We find that 36% of AD patients have elevated
      perceptual thresholds for left/right outward radial optic flow discrimination.
      This impairment is related to independent visual motion processing deficits
      affecting the perception of left/right motion-defined boundaries and in/out
      radial motion. Elevated optic flow thresholds in AD are correlated with greater
      difficulty in the Road Map test of visuospatial function (r = -0.5) and in on-the
      road driving tests (r = -0.83). When local motion cues are removed from optic
      flow, subjects must rely on the global pattern of motion. This reveals global
      pattern perceptual deficits that affect most AD patients (85%) and some normal
      elderly subjects (21%). This deficit might combine with impaired local motion
      processing to undermine the alternative perceptual strategies for visuospatial
      orientation. The greater prevalence of global pattern deficits suggests that it
      might precede local motion processing impairments, possibly relating to the
      sequence of early hippocampal and later posterior cortical damage that is typical
      of AD.

PMID- 11590118
TI  - Prefrontal cortex lesions augment the location-related firing properties of area
      TE/perirhinal cortex neurons in a working memory task.
AB  - It has previously been proposed that prefrontal cortex may have some role in
      keeping temporal cortex-based representations "on-line" during a working memory
      task. To test this hypothesis, the effects of electrolytic prefrontal cortex
      lesions on the firing of area TE and perirhinal cortex (PRC) neurons were
      examined while rats performed a delayed non-match to position task in the T-maze.
      The behavioural performance of control (n = 4) and lesioned (n = 4) animals were
      similar during this task, and many neurons displayed a statistically significant
      location-related variation in firing rate during the sample (44/56 neurons) and
      test (39/56 neurons) phases. Units from prefrontal-lesioned animals (82%) were
      more likely to display a significant variation in firing across the maze compared
      to controls (50%; P < 0.01), and to have more discrete location-related
      properties (50% of neurons) compared to the control (5%) group (P < 0.0005). This
      finding suggests that prefrontal cortex normally modulates the transmission
      and/or processing of spatial information in area TE/PRC during a working memory
      task. Modulation could be mediated through direct connections between the
      structures or via prefrontal control of subcortical structures. This finding has
      implications for our understanding of prefrontal-temporal involvement in memory
      and cognitive disorders.

PMID- 11590119
TI  - Oxidative stress causes abnormal accumulation of familial amyotrophic lateral
      sclerosis-related mutant SOD1 in transgenic Caenorhabditis elegans.
AB  - Mutations in the Cu/Zn superoxide dismutase (SOD1) genes are present in
      approximately 20% of families suffering from familial amyotrophic lateral
      sclerosis (FALS). Results from several transgenic studies in which FALS-related
      SOD1 mutations have been expressed have suggested that mutant SOD1 proteins
      induce cytotoxicity through a toxic gain of function, although the specific
      mechanism of this has not been fully clarified. To investigate the mechanism of
      toxicity induced by the mutant SOD1 associated with FALS, we generated transgenic
      Caenorhabditis elegans strains that contain wild-type and mutant human A4V, G37R
      and G93A SOD1 recombinant plasmids. The transgenic strains expressing mutant
      human SOD1 showed greater vulnerability to oxidative stress induced by 0.2 mM
      paraquat than a control that contained the wild-type human SOD1. In the absence
      of oxidative stress, mutant human SOD1 proteins were degraded more rapidly than
      the wild-type human SOD1 protein in C.elegans. In the presence of oxidative
      stress, however, this rapid degradation was inhibited, and the transgenic
      C.elegans co-expressing mutant human SOD1 and green fluorescent proteins (GFPs)
      in muscle tissues demonstrated discrete aggregates in the adult stage. These
      results suggest that oxidative damage inhibits the degradation of FALS-related
      mutant human SOD1 proteins, resulting in an aberrant accumulation of mutant
      proteins that might contribute to the cytotoxicity.

PMID- 11590120
TI  - A correlation between the relative predisposition of MHC class II alleles to type
      1 diabetes and the structure of their proteins.
AB  - In human type 1 diabetes (T1D) and in its murine model, the major
      histocompatibility complex (MHC) class II molecules, human leukocyte antigens
      (HLA)-DQ and -DR and their murine orthologues, IA and IE, are the major genetic
      determinants. In this report, we have ranked HLA class II molecule-associated T1D
      risk in a two-sided gradient from very high to very low. Very low risk
      corresponded to dominant protection from T1D. We predicted the protein structure
      of DQ by using the published crystal structures of different allotypes of the
      murine orthologue of DQ, IA. We discovered marked similarities both within, and
      cross species between T1D protective class II molecules. Likewise, the T1D
      predisposing molecules showed conserved similarities that contrasted with the
      shared patterns observed between the protective molecules. We also found striking
      inter-isotypic conservation between protective DQ, IA allotypes and protective
      DR4 subtypes. The data provide evidence for a joint action of the class II
      peptide-binding pockets P1, P4 and P9 in disease susceptibility and resistance
      with a main role for P9 in DQ/IA and for P1 and P4 in DR/IE. Overall, these
      results suggest shared epitope(s) in the target autoantigen(s), and common
      pathways in human and murine T1D.

PMID- 11590121
TI  - Conditional tissue-specific expression of the acid alpha-glucosidase (GAA) gene
      in the GAA knockout mice: implications for therapy.
AB  - Both enzyme replacement and gene therapy of lysosomal storage disorders rely on
      the receptor-mediated uptake of lysosomal enzymes secreted by cells, and for each
      lysosomal disorder it is necessary to select the correct cell type for
      recombinant enzyme production or for targeting gene therapy. For example, for the
      therapy of Pompe disease, a severe metabolic myopathy and cardiomyopathy caused
      by deficiency of acid alpha-glucosidase (GAA), skeletal muscle seems an obvious
      choice as a depot organ for local therapy and for the delivery of the recombinant
      enzyme into the systemic circulation. Using knockout mice with this disease and
      transgenes containing cDNA for the human enzyme under muscle or liver specific
      promoters controlled by tetracycline, we have demonstrated that the liver
      provided enzyme far more efficiently. The achievement of therapeutic levels with
      skeletal muscle transduction required the entire muscle mass to produce high
      levels of enzyme of which little found its way to the plasma, whereas liver,
      comprising <5% of body weight, secreted 100-fold more enzyme, all of which was in
      the active 110 kDa precursor form. Furthermore, using tetracycline regulation, we
      somatically induced human GAA in the knockout mice, and demonstrated that the
      skeletal and cardiac muscle pathology was completely reversible if the treatment
      was begun early.

PMID- 11590122
TI  - Aniridia-associated translocations, DNase hypersensitivity, sequence comparison
      and transgenic analysis redefine the functional domain of PAX6.
AB  - The transcription factor PAX6 plays a critical, evolutionarily conserved role in
      eye, brain and olfactory development. Homozygous loss of PAX6 function affects
      all expressing tissues and is neonatally lethal; heterozygous null mutations
      cause aniridia in humans and the Small eye (Sey) phenotype in mice. Several
      upstream and intragenic PAX6 control elements have been defined, generally
      through transgenesis. However, aniridia cases with chromosomal rearrangements far
      downstream of an intact PAX6 gene suggested a requirement for additional cis
      acting control for correct gene expression. The likely location of such elements
      is pinpointed through YAC transgenic studies. A 420 kb yeast artificial
      chromosome (YAC) clone, extending well beyond the most distant patient
      breakpoint, was previously shown to rescue homozygous Small eye lethality and
      correct the heterozygous eye phenotype. We now show that a 310 kb YAC clone,
      terminating just 5' of the breakpoint, fails to influence the Sey phenotypes.
      Using evolutionary sequence comparison, DNaseI hypersensitivity analysis and
      transgenic reporter studies, we have identified a region, >150 kb distal to the
      major PAX6 promoter P1, containing regulatory elements. Components of this
      downstream regulatory region drive reporter expression in distinct partial PAX6
      patterns, indicating that the functional PAX6 gene domain extends far beyond the
      transcription unit.

PMID- 11590123
TI  - Disabled early recruitment of antioxidant defenses in Friedreich's ataxia.
AB  - Friedreich's ataxia (FRDA) results from a generalized deficiency of mitochondrial
      iron-sulfur protein activity ascribed to mitochondrial iron overload. However,
      iron overload appears to be a late event in the disease. Here we show that
      neither superoxide dismutases nor the import iron machinery was induced by an
      endogenous oxidative stress in FRDA patients' fibroblasts in contrast to control
      cells. Superoxide dismutase activity was not induced in the heart of conditional
      frataxin-KO mice either. This suggests that continuous oxidative damage to iron
      sulfur clusters, resulting from hampered superoxide dismutase signaling, is
      causative of the mitochondrial deficiency and long term mitochondrial iron
      overload occurring in FRDA.

PMID- 11590124
TI  - Gestational, pathologic and biochemical differences between very long-chain acyl
      CoA dehydrogenase deficiency and long-chain acyl-CoA dehydrogenase deficiency in
      the mouse.
AB  - Although many patients have been found to have very long-chain acyl-CoA
      dehydrogenase (VLCAD) deficiency, none have been documented with long-chain acyl
      CoA dehydrogenase (LCAD) deficiency. In order to understand the metabolic
      pathogenesis of long-chain fatty acid oxidation disorders, we generated mice with
      VLCAD deficiency (VLCAD(-/-)) and compared their pathologic and biochemical
      phenotypes of mice with LCAD deficiency (LCAD(-/-)) and wild-type mice. VLCAD(-/
      ) mice had milder fatty change in liver and heart. Dehydrogenation of various
      acyl-CoA substrates by liver, heart and skeletal muscle mitochondria differed
      among the three genotypes. The results for liver were most informative as VLCAD(
      /-) mice had a reduction in activity toward palmitoyl-CoA and oleoyl-CoA (58 and
      64% of wild-type, respectively), whereas LCAD(-/-) mice showed a more profoundly
      reduced activity toward these substrates (35 and 32% of wild-type, respectively),
      with a significant reduction of activity toward the branched chain substrate 2,6
      dimethylheptanoyl-CoA. C(16) and C(18) acylcarnitines were elevated in bile,
      blood and serum of fasted VLCAD(-/-) mice, whereas abnormally elevated C(12) and
      C(14) acylcarnitines were prominent in LCAD(-/-) mice. Progeny with the combined
      LCAD(+/+)//VLCAD(+/-) genotype were over-represented in offspring from sires and
      dams heterozygous for both LCAD and VLCAD mutations. In contrast, no live mice
      with a compound LCAD(-/-)//VLCAD(-/-) genotype were detected.

PMID- 11590125
TI  - Defective satellite cells in congenital myotonic dystrophy.
AB  - In this study we have developed an in vitro cell culture system which displays
      the majority of the defects previously described for congenital myotonic
      dystrophy (CDM) muscle in vivo. Human satellite cells were isolated from the
      quadriceps muscles of three CDM fetuses with different clinical severity. By
      Southern blot analysis all three cultures were found to have approximately 2300
      CTG repeats. This CTG expansion was found to progressively increase in size
      during the proliferative life span, confirming an instability of this triplet in
      skeletal muscle cells. The CDM myoblasts and myotubes also showed abnormal
      retention of mutant RNA in nuclear foci, as well as modifications in their
      myogenic program. The proliferative capacity of the CDM myoblasts was reduced and
      a delay in fusion, differentiation and maturation was observed in the CDM
      cultures compared with unaffected myoblast cultures. The clinical severity and
      delayed maturation observed in the CDM fetuses were closely reflected by the
      phenotypic modifications observed in vitro. Since the culture conditions were the
      same, this suggests that the defects we have described are intrinsic to the
      program expressed by the myoblasts in the absence of any trophic factors.
      Altogether, our results demonstrate that satellite cells are defective in CDM and
      are probably implicated in the delay in maturation and muscle atrophy that has
      been described previously in CDM fetuses.

PMID- 11590126
TI  - A distant upstream promoter of the HNF-4alpha gene connects the transcription
      factors involved in maturity-onset diabetes of the young.
AB  - Maturity-onset diabetes of the young (MODY) is a monogenic, autosomal dominant
      subtype of early-onset diabetes mellitus due to defective insulin secretion by
      the pancreatic beta-cell in humans. Five different genes have been identified
      including those encoding the tissue-specific transcription factors expressed in
      pancreatic beta-cells, i.e. HNF-4alpha (MODY1), HNF-1alpha (MODY3), IPF-1 (also
      known as PDX-1, MODY4) and HNF-1beta (MODY5). Analyzing the transcription of the
      HNF-4alpha gene, we now identify an alternative promoter, P2, which is 46 kb 5'
      to the previously identified P1 promoter of the human gene. Based on RT-PCR this
      distant upstream P2 promoter represents the major transcription site in
      pancreatic beta-cells, but is also used in hepatic cells. Transfection assays
      with various deletions and mutants of the P2 promoter reveal functional binding
      sites for HNF-1alpha, HNF-1beta and IPF-1, the other transcription factors known
      to encode MODY genes. We demonstrate the significance of this alternative
      promoter in a large MODY family where a mutated IPF-1 binding site in the P2
      promoter of the HNF-4alpha gene co-segregates with diabetes (LOD score 3.25).
      These data suggest a regulatory network of the four MODY transcription factors
      interconnected at the distant upstream P2 promoter of the HNF-4alpha gene.

PMID- 11590127
TI  - Frataxin expression rescues mitochondrial dysfunctions in FRDA cells.
AB  - Friedreich's ataxia (FRDA) is the result of mutations in the nuclear-encoded
      frataxin gene, which is expressed in mitochondria. Several lines of evidence have
      suggested that frataxin is involved in mitochondrial iron homeostasis. We have
      transfected the frataxin gene into lymphoblasts of FRDA compound heterozygotes
      (FRDA-CH) with deficient frataxin expression to produce FRDA-CH-t cells in which
      message and protein are rescued to near-physiological levels. FRDA-CH cells were
      more sensitive to oxidative stress by challenge with free iron, hydrogen peroxide
      and the combination, consistent with a Fenton chemical mechanism of
      pathophysiology, and this sensitivity was rescued to control levels in FRDA-CH-t
      cells. Iron challenge caused increased mitochondrial iron levels in FRDA-CH
      cells, and a decreased mitochondrial membrane potential (MMP), both of which were
      rescued in FRDA-CH-t cells. The rescue of the low MMP, and high mitochondrial
      iron concentration by frataxin overexpression suggests that these cellular
      phenotypes are relevant to the central pathophysiological process in FRDA which
      is aggravated by exposure to free iron. However, even at physiological iron
      concentrations, FRDA-CH cells had decreased MMP as well as lower activities of
      aconitase and ICDH (two enzymes supporting MMP), and twice the level of filtrable
      mitochondrial iron (but no increase in total mitochondrial iron), and the
      observed phenotypes were either fully or partially rescued in FRDA-CH-t cells.
      Free iron is known to be toxic. The observation that frataxin deficiency (either
      directly or indirectly) causes an increase in filtrable mitochondrial iron
      provides a new hypothesis for the mechanism of cell death in this disease, and
      could be a target for therapy.

PMID- 11590128
TI  - Rabies virus glycoprotein pseudotyping of lentiviral vectors enables retrograde
      axonal transport and access to the nervous system after peripheral delivery.
AB  - In this report it is demonstrated for the first time that rabies-G envelope of
      the rabies virus is sufficient to confer retrograde axonal transport to a
      heterologous virus/vector. After delivery of rabies-G pseudotyped equine
      infectious anaemia virus (EIAV) based vectors encoding a marker gene to the rat
      striatum, neurons in regions distal from but projecting to the injection site,
      such as the dopaminergic neurons of the substantia nigra pars compacta, become
      transduced. This retrograde transport to appropriate distal neurons was also
      demonstrated after delivery to substantia nigra, hippocampus and spinal cord and
      did not occur when vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped
      vectors were delivered to these sites. In addition, peripheral administration of
      rabies-G pseudotyped vectors to the rat gastrocnemius muscle leads to gene
      transfer in motoneurons of lumbar spinal cord. In contrast the same vector
      pseudotyped with VSV-G transduced muscle cells surrounding the injection site,
      but did not result in expression in any cells in the spinal cord. Long-term
      expression was observed after gene transfer in the nervous system and a minimal
      immune response which, together with the possibility of non-invasive
      administration, greatly extends the utility of lentiviral vectors for gene
      therapy of human neurological disease.

PMID- 11590129
TI  - CLN3 protein is targeted to neuronal synapses but excluded from synaptic
      vesicles: new clues to Batten disease.
AB  - Batten disease (juvenile neuronal ceroid lipofuscinosis, JNCL), the most common
      neurodegenerative disease of childhood, is caused by mutations in the CLN3 gene
      encoding a putative transmembrane protein. The function of CLN3 is currently
      unknown but it has been shown to localize in the endosomal/lysosomal compartments
      of non-neuronal cells. In addition, several other intracellular localizations
      have been proposed and the controversy of the reports suggests that CLN3 may have
      different intracellular localization in different cell types. Batten disease
      severely affects neuronal cells but leaves other organs clinically unaffected,
      and thus it is of utmost importance to approach the disease mechanism by studying
      the expression and localization of CLN3 in the brain and neuronal cells. We have
      analysed here CLN3 in the mouse brain using in situ hybridization,
      immunohistochemical staining and western blot analysis of subcellular fractions.
      As visual deterioration is the hallmark of Batten disease we have set up primary
      retinal cultures from the mouse and analysed both endogenous mouse CLN3 and
      Semliki Forest virus-mediated human CLN3 localization using immunofluorescence
      staining and confocal microscopy. We demonstrate that CLN3 is abundantly
      expressed in neuronal cells, especially in the cortex, hippocampus and cerebellum
      of the adult mouse brain. Furthermore, our results indicate that in neurons CLN3
      is not solely a lysosomal protein. It is localized in the synaptosomes but,
      interestingly, is not targeted to the synaptic vesicles. The novel localization
      of CLN3 directs attention towards molecular alterations at the synapses. This
      should yield important clues about the mechanisms of neurodegeneration in Batten
      disease.

PMID- 11590130
TI  - Detecting differentially expressed genes in multiple tag sampling experiments:
      comparative evaluation of statistical tests.
AB  - The comparison of several statistical methods currently used for detection of
      differentially expressed genes was attempted both by a simulation approach and by
      the analysis of data sets of human expressed sequence tags, obtained from
      UniGene. In the simulated mixed case, mimicking a situation close to reality, the
      general chi(2) test was unexpectedly the most efficient in multiple tag sampling
      experiments, especially when dealing with variations affecting weakly expressed
      genes. On the other hand, Audic and Claverie's method proved the most efficient
      for detecting differences in gene expression when dealing with pairwise
      comparisons. By applying the above methods on UniGene-based data sets concerning
      two human kidney tumours compared with normal kidney tissue, three novel genes
      overexpressed in these tumours were identified. Software and additional
      information on statistical methodologies, simulation approach and data are
      available at http://telethon.bio.unipd.it/bioinfo/IDEG6/.

PMID- 11590131
TI  - Dysregulation of human brain microtubule-associated tau mRNA maturation in
      myotonic dystrophy type 1.
AB  - Intraneuronal aggregates of hyperphosphorylated tau proteins, referred to as
      pathological tau, are found in brain areas of demented patients affected by
      numerous different neurodegenerative disorders. We previously described a
      particular biochemical profile of pathological tau proteins in myotonic dystrophy
      type 1 (DM1). This multisystemic disorder is characterized by an unstable CTG
      repeat expansion in the 3'-untranslated region of the DM protein kinase gene. In
      the human central nervous system, tau proteins consist of six isoforms that
      differ by the presence or absence of the alternatively spliced exons 2, 3 and 10.
      Here we show that the pattern of tau isoforms aggregated in DM1 brain lesions is
      characteristic. It consists mainly of the aggregation of the shortest human tau
      isoform. A disruption in normal tau isoform expression consisting of a reduced
      expression of tau isoforms containing the exon 2 was observed at both the mRNA
      and protein levels. Large expanded CTG repeats were detected and showed marked
      somatic heterogeneity between DM1 cases and in cortical brains regions analysed.
      Our data suggest a relationship between the CTG repeat expansion and the
      alteration of tau expression showing that DM1 is a peculiar tauopathy.

PMID- 11590132
TI  - Genetic variation in the human urea transporter-2 is associated with variation in
      blood pressure.
AB  - The kidney, by regulating the volume of fluid in the body, plays a key role in
      regulating blood pressure (BP). The kidney uses primarily sodium and, to a lesser
      extent, urea to maintain the appropriate volume of fluid. Genetic variation in
      proteins that determine sodium reabsorption and excretion is known to
      significantly influence BP. However, the influence of genetic variation in urea
      transporters on BP has not been examined. We determined therefore whether
      nucleotide variation in the kidney-specific human urea transporter, HUT2, is
      associated with variation in BP. After determining the genomic structure of the
      coding sequence, seven single nucleotide polymorphisms (SNPs) were identified.
      Two of the SNPs result in Val/Ile and Ala/Thr amino acid substitutions at
      positions 227 and 357 in the HUT2 open reading frame, respectively. Another SNP
      is silent and four others are in introns or the 3' untranslated region. Over 1000
      hypertensive and low-normotensive individuals of Chinese origin were typed for
      five of these SNPs using a high-throughput genotyping method. The Ile227 and
      Ala357 alleles were associated with low diastolic BP in men but not women, with
      odds ratios 2.1 [95% confidence interval (CI) 1.5-2.7, P < 0.001] and 1.5 (95% CI
      1.2-1.8, P < 0.001), respectively. There was a similar trend for systolic BP, and
      odds ratios for the Ile227 and Ala357 alleles were 1.7 (95% CI 1.2-2.3, P =
      0.002) and 1.3 (95% CI 1.1-1.6, P = 0.007), respectively, in men.

PMID- 11590133
TI  - Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types
      1 and 2.
AB  - The phenotypes in myotonic dystrophy types 1 and 2 (DM1 and DM2) are similar,
      suggesting a shared pathophysiologic mechanism. DM1 is caused by expansion of a
      CTG repeat in the DMPK gene. Pathogenic effects of this mutation are likely to be
      mediated, at least in part, by the expanded CUG repeat in mutant mRNA. The mutant
      transcripts are retained in the nucleus in multiple discrete foci. We
      investigated the possibility that DM2 is also caused by expansion of a CTG repeat
      or related sequence. Analysis of DNA by repeat expansion detection methods, and
      RNA by ribonuclease protection, did not show an expanded CTG or CUG repeat in
      DM2. However, hybridization of muscle sections with fluorescence-labeled CAG
      repeat oligonucleotides showed nuclear foci in DM2 similar to those seen in DM1.
      Nuclear foci were present in all patients with symptomatic DM1 (n = 9) or DM2 (n
      = 9) but not in any disease controls or healthy subjects (n = 23). The foci were
      not seen with CUG- or GUC-repeat probes. Foci in DM2 were distinguished from DM1
      by lower stability of the probe-target duplex, suggesting that a sequence related
      to the DM1 CUG expansion accumulates in the DM2 nucleus. Muscleblind proteins,
      which interact with expanded CUG repeats in vitro, localized to the nuclear foci
      in both DM1 and DM2. These results support the idea that nuclear accumulation of
      mutant RNA is pathogenic in DM1, suggest that a similar disease process occurs in
      DM2, and point to a role for muscleblind in the pathogenesis of both disorders.

PMID- 11590134
TI  - A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts
      for the vast majority of incontinentia pigmenti mutations.
AB  - Incontinentia pigmenti (IP) is an X-linked dominant disorder characterized by
      abnormal skin pigmentation, retinal detachment, anodontia, alopecia, nail
      dystrophy and central nervous system defects. This disorder segregates as a male
      lethal disorder and causes skewed X-inactivation in female patients. IP is caused
      by mutations in a gene called NEMO, which encodes a regulatory component of the
      IkappaB kinase complex required to activate the NF-kappaB pathway. Here we report
      the identification of 277 mutations in 357 unrelated IP patients. An identical
      genomic deletion within NEMO accounted for 90% of the identified mutations. The
      remaining mutations were small duplications, substitutions and deletions. Nearly
      all NEMO mutations caused frameshift and premature protein truncation, which are
      predicted to eliminate NEMO function and cause cell lethality. Examination of
      families transmitting the recurrent deletion revealed that the rearrangement
      occurred in the paternal germline in most cases, indicating that it arises
      predominantly by intrachromosomal misalignment during meiosis. Expression
      analysis of human and mouse NEMO/Nemo showed that the gene becomes active early
      during embryogenesis and is expressed ubiquitously. These data confirm the
      involvement of NEMO in IP and will help elucidate the mechanism underlying the
      manifestation of this disorder and the in vivo function of NEMO. Based on these
      and other recent findings, we propose a model to explain the pathogenesis of this
      complex disorder.

PMID- 11590135
TI  - Control of nitric oxide dynamics by guanylate cyclase in its activated state.
AB  - Soluble guanylate cyclase (sGC) is the target of nitric oxide (NO) released by
      nitric-oxide synthase in endothelial cells, inducing an increase of cGMP
      synthesis in response. This heterodimeric protein possesses a regulatory subunit
      carrying a heme where NO binding occurs, while the second subunit harbors the
      catalytic site. The binding of NO and the subsequent breaking of the bond between
      the proximal histidine and the heme-Fe(2+) are assumed to induce conformational
      changes, which are the origin of the catalytic activation. At the molecular
      level, the activation and deactivation mechanisms are unknown, as is the dynamics
      of NO once in the heme pocket. Using ultrafast time-resolved absorption
      spectroscopy, we measured the kinetics of NO rebinding to sGC after
      photodissociation. The main spectral transient in the Soret band does not match
      the equilibrium difference spectrum of NO-liganded minus unliganded sGC, and the
      geminate rebinding was found to be monoexponential and ultrafast (tau = 7.5 ps),
      with a relative amplitude close to unity (0.97). These characteristics, so far
      not observed in other hemoproteins, indicate that NO encounters a high energy
      barrier for escaping from the heme pocket once the His-Fe(2+) bond has been
      cleaved; this bond does not reform before NO recombination. The deactivation of
      isolated sGC cannot occur by only simple diffusion of NO from the heme;
      therefore, several allosteric states may be inferred, including a desensitized
      one, to induce NO release. Thus, besides the structural change leading to
      activation, a consequence of the decoupling of the proximal histidine may also be
      to induce a change of the heme pocket distal geometry, which raises the energy
      barrier for NO escape, optimizing the efficiency of NO trapping. The non-single
      exponential character of the NO picosecond rebinding coexists only with the
      presence of the protein structure surrounding the heme, and the single
      exponential rate observed in sGC is very likely to be due to a closed
      conformation of the heme pocket. Our results emphasize the physiological
      importance of NO geminate recombination in hemoproteins like nitric-oxide
      synthase and sGC and show that the protein structure controls NO dynamics in a
      manner adapted to their function. This control of ligand dynamics provides a
      regulation at molecular level in the function of these enzymes.

PMID- 11590136
TI  - A potential role for human cohesin in mitotic spindle aster assembly.
AB  - The cohesin multiprotein complex containing SMC1, SMC3, Scc3 (SA), and Scc1
      (Rad21) is required for sister chromatid cohesion in eukaryotes. Although
      metazoan cohesin associates with chromosomes and was shown to function in the
      establishment of sister chromatid cohesion during interphase, the majority of
      cohesin was found to be off chromosomes and reside in the cytoplasm in metaphase.
      Despite its dissociation from chromosomes, however, microinjection of an antibody
      against human SMC1 led to disorganization of the metaphase plate and cell cycle
      arrest, indicating that human cohesin still plays an important role in metaphase.
      To address the mitotic function of human cohesin, the subcellular localization of
      cohesin components was reexamined in human cells. Interestingly, we found that
      cohesin localizes to the spindle poles during mitosis and interacts with NuMA, a
      spindle pole-associated factor required for mitotic spindle organization. The
      interaction with NuMA persists during interphase. Similar to NuMA, a significant
      amount of cohesin was found to associate with the nuclear matrix. Furthermore, in
      the absence of cohesin, mitotic spindle asters failed to form in vitro. Our
      results raise the intriguing possibility that in addition to its well
      demonstrated function in sister chromatid cohesion, cohesin may be involved in
      spindle assembly during mitosis.

PMID- 11590137
TI  - Molecular cloning and functional characterization of chicken toll-like receptors.
      A single chicken toll covers multiple molecular patterns.
AB  - Toll-like receptors (TLR) in the innate immune system have not been identified in
      non-mammalian vertebrates. Two types of TLR were cloned from a chicken bursa cDNA
      library using degenerate primers based on the consensus sequences of mouse and
      Drosophila Toll and designated as chicken TLR (chTLR) type 1 and type 2. Of the
      nine human TLRs reported to date, these chTLRs showed the highest homology to
      human TLR2. The extracellular regions of type 1 and type 2 contained a distinct
      approximately 200-amino acid stretch and were 45.3 and 46.3% homologous to that
      of human TLR2. The intracellular Toll/interleukin-1R homology domain of type 1
      and type 2 was perfectly identical to each other and highly homologous (80.7%) to
      that of human TLR2. Both types were widely detected by reverse transcriptase
      polymerase chain reaction and immunoblotting in various chicken organs,
      especially those rich in connective tissue. Both genes were mapped to chromosome
      4q1.1, suggesting that they arose by gene duplication. By reporter gene assay,
      type 2 and to a lesser extent type 1, selectively signaled the presence of
      mycoplasma macrophage-activating lipopeptide-2/M161Ag in the human embryonic
      kidney 293 cell system. Cotransfection of type 2 and human CD14 or MD-2 into
      human embryonic kidney 293 cells allowed the response to Escherichia coli
      lipopolysaccharide (LPS), whereas type 1 did not signal LPS or any other
      microbial components tested. These results indicated that chTLR type 2 covers two
      major microbe patterns, lipoproteins and LPS, which are regulated by TLR2 and
      TLR4 in mammals. In oviparous animals, the duplicated TLRs in the pattern
      recognition system may function for host-pathogen discrimination in a manner that
      is distinct from that in mammals.

PMID- 11590138
TI  - Disulfide connectivity of recombinant C-terminal region of human thrombospondin
      2.
AB  - The thrombospondin (TSP) family of extracellular glycoproteins consists of five
      members in vertebrates, TSP1 to -4 and TSP5/cartilage oligomeric matrix protein,
      and a single member in Drosophila. TSPs are modular multimeric proteins. The C
      terminal end of a monomer consists of 3-6 EGF-like modules; seven tandem 23-, 36
      , or 38-residue aspartate-rich, Ca(2+)-binding repeats; and an approximately 230
      residue C-terminal sequence. The Ca(2+)-binding repeats and C-terminal sequence
      are spaced almost exactly the same in different TSPs and share many blocks of
      identical residues. We studied the C-terminal portion of human TSP2 from the
      third EGF-like module through the end of the protein (E3CaG2). E3CaG2, CaG2
      lacking the EGF module, and Ca2 composed of only the Ca(2+)-binding repeats were
      expressed using recombinant baculoviruses and purified from conditioned media of
      insect cells. As previously described for intact TSP1, E3CaG2 bound Ca(2+) in a
      cooperative manner as assessed by equilibrium dialysis, and its circular
      dichroism spectrum was sensitive to the presence of Ca(2+). Mass spectrometry of
      the recombinant proteins digested with endoproteinase Asp-N revealed that
      disulfide pairing of the 18 cysteines in the Ca(2+)-binding repeats and C
      terminal sequence is sequential, i.e. a 1-2, 3-4, 5-6, etc., pattern.

PMID- 11590139
TI  - Enhanced expression of the human multidrug resistance protein 3 by bile salt in
      human enterocytes. A transcriptional control of a plausible bile acid
      transporter.
AB  - The enterohepatic circulation is essential for the maintenance of bile acids and
      cholesterol homeostasis. The ileal bile acid transporter on the apical membrane
      of enterocytes mediates the intestinal uptake of bile salts, but little is known
      about the bile salt secretion from the basolateral membrane of enterocytes into
      blood. In the basolateral membrane of enterocytes, an ATP-binding cassette
      transporter, multidrug resistance protein 3 (MRP3), is expressed, which has the
      ability to transport bile salts. We hypothesized that MRP3 might play a role in
      the enterohepatic circulation of bile salts by transporting them from enterocytes
      into circulating blood through the up-regulation of MRP3 expression, so we
      investigated the transcriptional control of MRP3 in response to bile salts. MRP3
      mRNA levels were increased about 3-fold in human colon cells by chenodeoxycholic
      acid (CDCA), in a dose- and time-dependent manner. In the promoter assay, the
      promoter activity of MRP3 was increased about 3-fold over the basal promoter
      activity when treated with CDCA, and the putative bile salt-responsive elements
      exist in the region -229/-138 including two alpha-1 fetoprotein transcription
      factor (FTF)-like elements. Constructs with a specific mutation in the consensus
      sequence of FTF elements showed no increase in basal transcriptional activity
      following CDCA treatment. In electrophoretic mobility shift assay with nuclear
      extracts, specific binding of FTF to FTF-like elements was observed when treated
      with CDCA. The expression of FTF mRNA levels were also markedly enhanced in
      response to CDCA, and overexpression of FTF specifically activated the MRP3
      promoter activity about 4-fold over the basal promoter activity. FTF thus might
      play a key role not only in the bile salt synthetic pathway in hepatocytes but
      also in the bile salt excretion pathway in enterocytes through the regulation of
      MRP3 expression. MRP3 may contribute as a plausible bile salt-exporting
      transporter to the enterohepatic circulation of bile salts.

PMID- 11590140
TI  - Tenascin-C aptamers are generated using tumor cells and purified protein.
AB  - Tenascin-C (TN-C) is an extracellular matrix protein that is overexpressed during
      tissue remodeling processes, including tumor growth. To identify an aptamer for
      testing as a tumor-selective ligand, SELEX (systematic evolution of ligands by
      exponential enrichment) procedures were performed using both TN-C and TN-C
      expressing U251 glioblastoma cells. The different selection techniques yielded TN
      C aptamers that are related in sequence. In addition, a crossover procedure that
      switched from tumor cell to purified protein selections was effective in
      isolating two high-affinity TN-C aptamers. When targeting tumor cells in vitro,
      the observed propensity of naive oligonucleotide pools to evolve TN-C aptamers
      may be due to the abundance of this protein. In vivo, TN-C abundance may also be
      well suited for aptamer accumulation in the tumor milieu. A size-minimized and
      nuclease-stabilized aptamer, TTA1, binds to the fibrinogen-like domain of TN-C
      with an equilibrium dissociation constant (K(d)) of 5 x 10(-9) m. At 13 kDa, this
      aptamer is intermediate in size between peptides and single chain antibody
      fragments, both of which are superior to antibodies for tumor targeting because
      of their smaller size. TTA1 defines a new class of ligands that are intended for
      targeted delivery of radioisotopes or chemical agents to diseased tissues.

PMID- 11590141
TI  - Constitutive activation of NF-kappa B and secretion of interleukin-8 induced by
      the G protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus involve
      G alpha(13) and RhoA.
AB  - The Kaposi's sarcoma herpesvirus (KSHV) open reading frame 74 encodes a G protein
      coupled receptor (GPCR) for chemokines. Exogenous expression of this
      constitutively active GPCR leads to cell transformation and vascular overgrowth
      characteristic of Kaposi's sarcoma. We show here that expression of KSHV-GPCR in
      transfected cells results in constitutive transactivation of nuclear factor kappa
      B (NF-kappa B) and secretion of interleukin-8, and this response involves
      activation of G alpha(13) and RhoA. The induced expression of a NF-kappa B
      luciferase reporter was partially reduced by pertussis toxin and the G beta gamma
      scavenger transducin, and enhanced by co-expression of G alpha(13) and to a
      lesser extent, G alpha(q). These results indicate coupling of KSHV-GPCR to
      multiple G proteins for NF-kappa B activation. Expression of KSHV-GPCR led to
      stress fiber formation in NIH 3T3 cells. To examine the involvement of the G
      alpha(13)-RhoA pathway in KSHV-GPCR-mediated NF-kappa B activation, HeLa cells
      were transfected with KSHV-GPCR alone and in combination with the regulator of G
      protein signaling (RGS) from p115RhoGEF or a dominant negative RhoA(T19N). Both
      constructs, as well as the C3 exoenzyme from Clostritium botulinum, partially
      reduced NF-kappa B activation by KSHV-GPCR, and by a constitutively active G
      alpha(13)(Q226L). KSHV-GPCR-induced NF-kappa B activation is accompanied by
      increased secretion of IL-8, a function mimicked by the activated G alpha(13) but
      not by an activated G alpha(q)(Q209L). These results suggest coupling of KSHV
      GPCR to the G alpha(13)-RhoA pathway in addition to other G proteins.

PMID- 11590142
TI  - The human protein HSPC021 interacts with Int-6 and is associated with eukaryotic
      translation initiation factor 3.
AB  - The Int-6 protein has been shown to be a subunit of eukaryotic translation
      initiation factor 3 (eIF3) and to play a role in the control of cell growth. By
      immunoprecipitation experiments and mass spectrometry analyses, we identified a
      human protein previously known as HSPC021 that is associated with Int-6. Exposure
      of Jurkat cells to the phosphatase inhibitor H(2)O(2) triggers a marked
      phosphorylation on tyrosine of HSPC021. Several experiments were performed to
      evaluate whether this protein is associated with eIF3. It was observed that
      HSPC021 coelutes with Int-6 and eIF3 in gel filtration, coimmunoprecipitates with
      eIF3, and is incorporated into eIF3 both in rabbit reticulocyte lysates and in
      COS7 cells. A direct protein-protein interaction occurs between HSPC021 and Int
      6, but the analysis of different mutants of HSPC021 indicated that a larger
      region of the protein is necessary for incorporation into eIF3 as compared with
      binding to Int-6. Taken together, our results establish that HSPC021 is tightly
      associated with the mammalian translation initiation factor eIF3. Analysis of the
      primary sequence of HSPC021 from different species revealed the presence of a
      tetratricopeptide repeat, a proteasome-COP9 (constitutive photomorphogenesis 9)
      signalosome-initiation factor 3 domain along with a Pumilio FBF repeat. These
      protein motifs are also present in subunits of eIF3, of the lid of the 26 S
      proteasome, and of the COP9 signalosome.

PMID- 11590143
TI  - The formin/diaphanous-related protein, FHOS, interacts with Rac1 and activates
      transcription from the serum response element.
AB  - FHOS is a member of the formin homology (FH) family of proteins and is expressed
      at high levels in splenic cells. FH proteins link cellular signaling pathways to
      the actin cytoskeleton and serum response factor-dependent transcription. In
      these studies, the role of FHOS in Rho family GTPase signaling pathways was
      analyzed. FHOS interacted with the polybasic domain in the Rac1 C terminus in a
      guanine nucleotide-independent manner but did not interact with RhoA, Cdc42Hs,
      Rac2, or Rac3. Intramolecular autoinhibitory interactions between the C terminus
      of FHOS and an N-terminal region partially overlapping the Rac1 interaction
      domain were also identified. FHOS truncation mutants lacking the N- or C-terminal
      autoregulatory domains stimulated transcription of a c-fos serum response element
      (SRE)-driven reporter. Overexpression of wild-type and mutant (N17 and V12) Rac1
      proteins repressed SRE induction by the N-terminal FHOS deletion mutant but not
      by the C-terminal FHOS deletion mutant. Immunofluorescence studies indicated that
      the localization of the mutant FHOS proteins might contribute to their
      differential responses to Rac1. Wild-type FHOS and the N-terminal deletion mutant
      localized to the perinuclear region and membrane edges. In contrast, the C
      terminal FHOS mutants were diffusely localized. These data suggest that FHOS
      induces transcription from SREs by multiple pathways and that Rac1 may influence
      the course of some FHOS-induced signaling events.

PMID- 11590144
TI  - Neuregulin rescues PC12-ErbB4 cells from cell death induced by H(2)O(2).
      Regulation of reactive oxygen species levels by phosphatidylinositol 3-kinase.
AB  - Neuregulins (NRGs), a large family of transmembrane polypeptide growth factors,
      mediate various cellular responses depending on the cell type and receptor
      expression. We previously showed that NRG mediates survival of PC12-ErbB4 cells
      from apoptosis induced by serum deprivation or tumor necrosis factor-alpha
      treatment. In the present study we show that NRG induces a significant protective
      effect from H(2)O(2)-induced death. This effect of NRG is mediated by the
      phosphatidylinositol 3-kinase (PI3K)-signaling pathway since NRG failed to rescue
      cells from H(2)O(2) insult in the presence of the PI3K inhibitor, LY294002.
      Furthermore, the downstream effector of PI3K, protein kinase B/AKT, is activated
      by NRG in the presence of H(2)O(2), and protein kinase B/AKT activation is
      inhibited by LY294002. In addition, our results demonstrate that reactive oxygen
      species (ROS) elevation induced by H(2)O(2) is inhibited by NRG. LY294002, which
      blocks NRG-mediated rescue, increases ROS levels. Moreover, both H(2)O(2)-induced
      ROS elevation and cell death are reduced by expression of activated PI3K. These
      results suggest that PI3K-dependent pathways may regulate toxic levels of ROS
      generated by oxidative stress.

PMID- 11590145
TI  - Transforming growth factor beta regulates parathyroid hormone-related protein
      expression in MDA-MB-231 breast cancer cells through a novel Smad/Ets synergism.
AB  - The majority of breast cancers metastasizing to bone secrete parathyroid hormone
      related protein (PTHrP). PTHrP induces local osteolysis that leads to activation
      of bone matrix-borne transforming growth factor beta (TGF beta). In turn, TGF
      beta stimulates PTHrP expression and, thereby, accelerates bone destruction. We
      studied the mechanism by which TGF beta activates PTHrP in invasive MDA-MB-231
      breast cancer cells. We demonstrate that TGF beta 1 up-regulates specifically the
      level of PTHrP P3 promoter-derived RNA in an actinomycin D-sensitive fashion.
      Transient transfection studies revealed that TGF beta 1 and its effector Smad3
      are able to activate the P3 promoter. This effect depended upon an AGAC box and a
      previously described Ets binding site. Addition of Ets1 greatly enhanced the
      Smad3/TGF beta-mediated activation. Ets2 had also some effect, whereas other Ets
      proteins, Elf-1, Ese-1, and Erf-1, failed to cooperate with Smad3. In comparison,
      Ets1 did not increase Smad3/TGF beta-induced stimulation of the TGF beta
      responsive plasminogen activator inhibitor 1 (PAI-1) promoter. Smad3 and Smad4
      were able to specifically interact with the PTHrP P3-AGAC box and to bind to the
      P3 promoter together with Ets1. Inhibition of endogenous Ets1 expression by
      calphostin C abrogated TGF beta-induced up-regulation of the P3 transcript,
      whereas it did not affect the TGF beta effect on PAI expression. In TGF beta
      receptor II- and Ets1-deficient, noninvasive MCF-7 breast cancer cells, TGF beta
      1 neither influenced endogenous PTHrP expression nor stimulated the PTHrP P3
      promoter. These data suggest that TGF beta activates PTHrP expression by
      specifically up-regulating transcription from the PTHrP P3 promoter through a
      novel Smad3/Ets1 synergism.

PMID- 11590146
TI  - Cloning of human junctional adhesion molecule 3 (JAM3) and its identification as
      the JAM2 counter-receptor.
AB  - We have identified a third member of the junctional adhesion molecule (JAM)
      family. At the protein level JAM3 displays 36 and 32% identity to JAM2 and JAM1,
      respectively. The coding region is distributed over 9 exons and maps to
      chromosome 11q25. The gene shows widespread tissue expression with higher levels
      apparent in the kidney, brain, and placenta. At the cellular level we show
      expression of JAM3 transcript within endothelial cells. Our major finding is that
      JAM3 and JAM2 are binding partners. Thus, JAM3 ectodomain binds firmly to JAM2
      Fc. This heterotypic interaction is maintained when JAM3-Fc is used to capture
      Chinese hamster ovary cells expressing full-length JAM2. In static adhesion
      assays we show that JAM3 is unable to bind to leukocyte cell lines. This is
      consistent with the lack of JAM2 expression. However, using JAM2-Fc pull-down
      experiments in combination with polyclonal anti-JAM3 serum, we demonstrate that
      JAM3 is the previously uncharacterized 43-kDa counter-receptor that mediates JAM2
      adhesion to T cells. Most significantly we demonstrate up-regulation of JAM3
      protein on peripheral blood lymphocytes following activation. Finally we show the
      utility of JAM3 ectodomain as an inhibitor of JAM2 adhesion.

PMID- 11590147
TI  - Cyclin D1 overexpression induces progestin resistance in T-47D breast cancer
      cells despite p27(Kip1) association with cyclin E-Cdk2.
AB  - Long-term growth inhibition, arrest in G(1) phase and reduced activity of both
      cyclin D1-Cdk4 and cyclin E-Cdk2 are elicited by progestin treatment of breast
      cancer cells in culture. Decreased cyclin expression, induction of p18(INK4c) and
      increased association of the CDK inhibitors p21(WAF1/Cip1) and p27(Kip1) with
      cyclin E-Cdk2 have been implicated in these responses. To determine the role of
      decreased cyclin expression, T-47D human breast cancer cells constitutively
      expressing cyclin D1 or cyclin E were treated with the progestin ORG 2058.
      Overexpression of cyclin E had only a modest effect on growth inhibition.
      Although cyclin E expression was maintained during progestin treatment, cyclin E
      Cdk2 activity decreased by approximately 60%. This was accompanied by p27(Kip1)
      association with cyclin E-Cdk2, indicating that both cyclin E down-regulation and
      p27(Kip1) recruitment contribute to the decrease in activity. In contrast,
      overexpression of cyclin D1 induced progestin resistance and cell proliferation
      continued despite decreased cyclin E-Cdk2 activity. Progestin treatment of cyclin
      D1-overexpressing cells was associated with increased p27(Kip1) association with
      cyclin E-Cdk2. Thus the ability of cyclin D1 to confer progestin resistance does
      not depend on sequestration of p27(Kip1) away from cyclin E-Cdk2, providing
      evidence for a critical function of cyclin D1 other than as a high-capacity
      "sink" for p27(Kip1). These data indicate that regulation of cyclin D1 is a
      critical element of progestin inhibition in breast cancer cells and suggest that
      breast cancers overexpressing cyclin D1 may respond poorly to progestin therapy.

PMID- 11590148
TI  - The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B
      coactivator function.
AB  - Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against
      septic shock, diabetes type I, stroke, and inflammation. We report that primary
      cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional
      activation induced by different stimuli involved in inflammatory and genotoxic
      stress signaling. PARP-1 was also required for p65-mediated transcriptional
      activation. PARP-1 enzymatic inhibitors did not inhibit the transcriptional
      activation of a kappa B-dependent reporter gene in wild type cells. Remarkably,
      neither the enzymatic activity nor the DNA binding activity of PARP-1 was
      required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells
      complemented with different PARP-1 mutants. However, PARP-1 interacted in vitro
      directly with both subunits of NF-kappa B (p50 and p65), and mapping of the
      interaction domains revealed that both subunits bind to different PARP-1 domains.
      Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity
      interacted comparably to the wild type PARP-1 with p65 or p50. Finally, we showed
      that PARP-1 is activating the natural inducible nitric-oxide synthase and P
      selectin promoter in a kappa B-dependent manner upon stimulation of the cells
      with inflammatory stimuli or cotransfection of p65. Our results provide evidence
      that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct
      protein-protein interaction with both subunits of NF-kappa B is required for its
      coactivator function, thus expanding the role of PARP-1 as an essential and novel
      classical transcriptional coactivator for kappa B-dependent gene expression in
      vivo.

PMID- 11590149
TI  - Rab5-dependent trafficking of the m4 muscarinic acetylcholine receptor to the
      plasma membrane, early endosomes, and multivesicular bodies.
AB  - The m4 subtype of muscarinic acetylcholine receptor regulates many physiological
      processes and is a novel therapeutic target for neurologic and psychiatric
      disorders. However, little is known about m4 regulation because of the lack of
      pharmacologically selective ligands. A crucial component of G protein-coupled
      receptor regulation is intracellular trafficking. We thus used subtype-specific
      antibodies and quantitative immunocytochemistry to characterize the intracellular
      trafficking of m4. We show that following carbachol stimulation, m4 co-localizes
      with transferrin, and the selective marker of early endosomes, EEA1. In addition,
      m4 intracellular localization depends on Rab5 activity. The dominant negative
      Rab5S34N inhibits m4 endocytosis initially following carbachol stimulation, and
      reduces the size of m4 containing vesicles. The constitutively active Rab5Q79L
      enhances m4 intracellular distribution, even in unstimulated cells. Rab5Q79L also
      produces strikingly enlarged vacuoles, which by electron microscopy contain
      internal vesicles, suggesting that they are multivesicular bodies. m4 localizes
      both to the perimeter and interior of these vacuoles. In contrast, transferrin
      localizes only to the vacuole perimeter, demonstrating divergence of m4
      trafficking from the pathway followed by constitutively endocytosed transferrin.
      We thus suggest a novel model by which multivesicular bodies sort G protein
      coupled receptors from a transferrin-positive recycling pathway to a
      nonrecycling, possibly degradative pathway.

PMID- 11590150
TI  - Molecular cloning of a functional allatostatin gut/brain receptor and an
      allatostatin preprohormone from the silkworm Bombyx mori.
AB  - The cockroach-type or A-type allatostatins are inhibitory insect neuropeptides
      with the C-terminal sequence Tyr/Phe-X-Phe-Gly-Leu-NH(2). Here, we have cloned an
      A-type allatostatin receptor from the silkworm Bombyx mori (BAR). BAR is 361
      amino acid residues long, has seven transmembrane domains, shows 60% amino acid
      residue identity with the first Drosophila allatostatin receptor (DAR-1), and 48%
      identity with the second Drosophila allatostatin receptor (DAR-2). The BAR gene
      has two introns and three exons. These two introns coincide with and have the
      same intron phasing as two introns in the DAR-1 and DAR-2 genes, showing that the
      three receptors are not only structurally but also evolutionarily related.
      Furthermore, we have cloned a Bombyx allatostatin preprohormone that contains
      eight different A-type allatostatins. Chinese hamster ovary cells permanently
      transfected with BAR DNA react on the addition of 4 x 10(-9)M Bombyx A-type
      allatostatins with a second messenger cascade (measured as bioluminescence),
      showing that BAR is a functional A-type allatostatin receptor. Southern blots
      suggest that Bombyx has at least one other BAR-related gene in addition to the
      BAR gene described in this paper. Northern blots and quantitative reverse
      transcriptase-polymerase chain reaction of different larval tissues show that BAR
      mRNA is mainly expressed in the gut and to a much lesser extent in the brain. To
      our knowledge, this is the first report on the molecular cloning and functional
      expression of an insect gut/brain peptide hormone receptor.

PMID- 11590151
TI  - Residual structure and dynamics in Parkinson's disease-associated mutants of
      alpha-synuclein.
AB  - alpha-Synuclein (alpha S) is a pre-synaptic protein that has been implicated as a
      possible causative agent in the pathogenesis of Parkinson's disease (PD). Two
      autosomal dominant missense mutations in the alpha S gene are associated with
      early onset PD. Because alpha S is found in an aggregated fibrillar form in the
      Lewy body deposits characteristic of Parkinson's patients, aggregation of the
      protein is believed to be related to its involvement in the disease process. The
      wild type (WT) and early onset mutants A30P and A53T display diverse in vitro
      aggregation kinetics even though the gross physicochemical and morphological
      properties of the mutants are highly similar. We used high resolution solution
      NMR spectroscopy to compare the structural and dynamic properties of the A53T and
      A30P mutants with those of WT alpha S in the free state. We found that the A30P
      mutation disrupts a region of residual helical structure that exists in the WT
      protein, whereas the A53T mutation results in a slight enhancement of a small
      region around the site of mutation with a preference for extended conformations.
      Based on these results and on the anticipated effects of these mutations on
      elements of secondary structure, we proposed a model of how these two PD-linked
      mutations influence alpha S fibril formation that is consistent with the
      documented differences in the fibrillization kinetics of the two mutants.

PMID- 11590152
TI  - Pex18p is constitutively degraded during peroxisome biogenesis.
AB  - Pex18p and Pex21p are structurally related yeast peroxins (proteins required for
      peroxisome biogenesis) that are partially redundant in function. One or the other
      is essential for the import into peroxisomes of proteins with type 2 peroxisomal
      targeting sequences (PTS2). These sequences bind to the soluble PTS2 receptor,
      Pex7p, which in turn binds to Pex18p (or Pex21p or possibly both). Here we show
      that Pex18p is constitutively degraded with a half-time of less than 10 min in
      wild-type Saccharomyces cerevisiae. This degradation probably occurs in
      proteasomes, because it requires the related ubiquitin-conjugating enzymes Ubc4p
      and Ubc5p and occurs normally in a mutant lacking the Pep4p vacuolar protease.
      The turnover of Pex18p stops, and Pex18p accumulates to a much higher than normal
      abundance in pex mutants in which the import of all peroxisomal matrix proteins
      is blocked. This includes mutants that lack peroxins involved in receptor docking
      at the membrane (Deltapex13 or Deltapex14), a mutant that lacks the peroxisomal
      member of the E2 family of ubiquitin-conjugating enzymes (Deltapex4), and others
      (Deltapex1). This stabilization in a variety of pex mutants indicates that Pex18p
      turnover is associated with its normal function. A Pex18p-Pex7p complex is
      detected by immunoprecipitation in wild type cells, and its abundance increases
      considerably in the Deltapex14 peroxisome biogenesis mutant. Cells that lack
      Pex7p fail to stabilize and accumulate Pex18p, indicating an important role for
      complex formation in the stabilization. Mono- and diubiquitinated forms of Pex18p
      are detected in wild-type cells, and there is no Pex18p turnover in a yeast doa4
      mutant in which ubiquitin homeostasis is defective. These data represent, to the
      best of our knowledge, the first instance of an organelle biogenesis factor that
      is degraded constitutively and rapidly.

PMID- 11590153
TI  - (Xeno)estrogen sensitivity of smooth muscle BK channels conferred by the
      regulatory beta1 subunit: a study of beta1 knockout mice.
AB  - Estrogen and xenoestrogens (i.e. agents that are not steroids but possess
      estrogenic activity) increase the open probability (P(o)) of large conductance
      Ca(2+)-activated K(+) (BK) channels in smooth muscle. The mechanism of action may
      involve the regulatory beta1 subunit. We used beta1 subunit knockout (beta1-/-)
      mice to test the hypothesis that the regulatory beta1 subunit is essential for
      the activation of BK channels by tamoxifen, 4-OH tamoxifen (a major biologically
      active metabolite), and 17beta-estradiol in native myocytes. Patch clamp
      recordings demonstrate BK channels from beta1-/- mice were similar to wild type
      with the exception of markedly reduced Ca(2+)/voltage sensitivity and faster
      activation kinetics. In wild type myocytes, (xeno)estrogens increased NP(o) (P(o)
      x the number of channels, N), shifted the voltage of half-activation (V(12)) to
      more negative potentials, and decreased unitary conductance. These effects were
      non-genomic and direct, because they were rapid, reversible, and observed in cell
      free patches. None of the (xeno)estrogens increased the NP(o) of BK channels from
      beta1-/- mice, but all three agents decreased single channel conductance. Thus,
      (xeno)estrogens increase BK NP(o) through a mechanism involving the beta1
      subunit. The decrease in conductance did not require the beta1 subunit and
      probably reflects an interaction with the pore-forming alpha subunit. We
      demonstrate regulation of smooth muscle BK channels by physiological (steroid
      hormones) and pharmacological (chemotherapeutic) agents and reveal the critical
      role of the beta1 subunit in these responses in native myocytes.

PMID- 11590154
TI  - Diffusion of phycobilisomes on the thylakoid membranes of the cyanobacterium
      Synechococcus 7942. Effects of phycobilisome size, temperature, and membrane
      lipid composition.
AB  - A variant of fluorescence recovery after photobleaching allows us to observe the
      diffusion of photosynthetic complexes in cyanobacterial thylakoid membranes in
      vivo. The unicellular cyanobacterium Synechococcus sp. PCC7942 is a wonderful
      model organism for fluorescence recovery after photobleaching, because it has a
      favorable membrane geometry and is well characterized and transformable. In
      Synechococcus 7942 (as in other cyanobacteria) we find that photosystem II is
      immobile, but phycobilisomes diffuse rapidly on the membrane surface. The
      diffusion coefficient is 3 x 10(-10) cm(2) s(-1) at 30 degrees C. This shows that
      the association of phycobilisomes with reaction centers is dynamic; there are no
      stable phycobilisome-reaction center complexes in vivo. We report the effects of
      mutations that change the phycobilisome size and membrane lipid composition. 1)
      In a mutant with no phycobilisome rods, the phycobilisomes remain mobile with a
      slightly faster diffusion coefficient. This confirms that the diffusion we
      observe is of intact phycobilisomes rather than detached rod elements. The faster
      diffusion coefficient in the mutant indicates that the rate of diffusion is
      partly determined by the phycobilisome size. 2) The temperature dependence of the
      phycobilisome diffusion coefficient indicates that the phycobilisomes have no
      integral membrane domain. It is likely that association with the membrane is
      mediated by multiple weak interactions with lipid head groups. 3) Changing the
      lipid composition of the thylakoid membrane has a dramatic effect on
      phycobilisome mobility. The results cannot be explained in terms of changes in
      the fluidity of the membrane; they suggest that lipids play a role in controlling
      phycobilisome-reaction center interaction.

PMID- 11590155
TI  - Autoinhibition of mixed lineage kinase 3 through its Src homology 3 domain.
AB  - Mixed lineage kinase 3 (MLK3) is a serine/threonine protein kinase that functions
      as a mitogen-activated protein kinase kinase kinase to activate the c-Jun NH(2)
      terminal kinase pathway. MLK3 has also been implicated as an I kappa B kinase
      kinase in the activation of NF-kappa B. Amino-terminal to its catalytic domain,
      MLK3 contains a Src homology 3 (SH3) domain. SH3 domains harbor three highly
      conserved aromatic amino acids that are important for ligand binding. In this
      study, we mutated one of these corresponding residues within MLK3 to deliberately
      disrupt the function of its SH3 domain. This SH3-defective mutant of MLK3
      exhibited increased catalytic activity compared with wild type MLK3 suggesting
      that the SH3 domain negatively regulates MLK3 activity. We report herein that the
      SH3 domain of MLK3 interacts with full-length MLK3, and we have mapped the site
      of interaction to a region between the zipper and the Cdc42/Rac interactive
      binding motif. Interestingly, the SH3-binding region contains not a proline-rich
      sequence but, rather, a single proline residue. Mutation of this sole proline
      abrogates SH3 binding and increases MLK3 catalytic activity. Taken together,
      these data demonstrate that MLK3 is autoinhibited through its SH3 domain. The
      critical proline residue in the SH3-binding site of MLK3 is conserved in the
      closely related family members, MLK1 and MLK2, suggesting a common autoinhibitory
      mechanism among these kinases. Our study has revealed the first example of SH3
      domain-mediated autoinhibition of a serine/threonine kinase and provides insight
      into the regulation of the mixed lineage family of protein kinases.

PMID- 11590156
TI  - Active site blockade of factor VIIa alters its intracellular distribution.
AB  - Factor VIIa binding to tissue factor on cell surfaces not only triggers the
      coagulation cascade but also induces various intracellular responses that may
      contribute to many pathophysiological processes. Active site-inhibited factor
      VIIa, similar to factor VIIa, binds to tissue factor on cell surfaces and
      subsequently gets internalized and degraded. At present, it is unknown whether
      factor VIIa and active site-inhibited factor VIIa undergo a similar intracellular
      processing. The data presented herein show that although a fraction of both the
      internalized factor VIIa and active site-inhibited factor VIIa recycle back to
      the cell surface, the amount of active site-inhibited factor VIIa recycled back
      to the cell surface was substantially higher than that of factor VIIa.
      Furthermore, internalized factor VIIa and not active site-inhibited factor VIIa
      associates with nuclear fractions. Factor VIIa associated with the nuclear
      fraction was intact and functionally active. In contrast to factor VIIa, tissue
      factor is not found in the nuclear fraction. Additional studies show that the
      internalized factor VIIa specifically associates with cytoskeletal proteins,
      actin, and tubulin. In summary, the present data reveal that despite the common
      pathway of tissue factor-mediated processing, considerable differences exist in
      the trafficking of factor VIIa and active site-inhibited factor VIIa in
      fibroblasts.

PMID- 11590157
TI  - Regulation of apoptosis by vitamin C. Specific protection of the apoptotic
      machinery against exposure to chlorinated oxidants.
AB  - We have investigated the ability of intracellular vitamin C to protect human
      umbilical vein endothelial cells from exposure to hypochlorous acid (HOCl) and a
      range of derived chloramines. Ascorbate provided minimal protection against the
      cytotoxicity induced by these oxidants, as measured by propidium iodide uptake.
      In contrast, there was a marked effect on apoptosis, monitored by caspase-3
      activation and phosphatidylserine exposure. Extended incubation of the cells with
      glycine chloramine or histamine chloramine completely blocked apoptosis initiated
      in the cells by serum withdrawal. This effect was significantly abrogated by
      ascorbate. Inhibition of apoptosis required the oxidant to be present for an
      extended period after serum withdrawal and occurred prior to caspase-3
      activation. General protection of thiols by ascorbate was not responsible for the
      protection of apoptosis, because intracellular oxidation by HOCl or chloramines
      was not prevented in supplemented cells. The results suggest a new role for
      vitamin C in the regulation of apoptosis. We propose that, by protection of an
      oxidant-sensitive step in the initiation phase, ascorbate allows apoptosis to
      proceed in endothelial cells under sustained oxidative stress.

PMID- 11590158
TI  - Feedback inhibition of poly(A)-binding protein mRNA translation. A possible
      mechanism of translation arrest by stalled 40 S ribosomal subunits.
AB  - An adenine-rich cis element at the 5'-untranslated region (UTR) of Pabp1 mRNA is
      able to inhibit translation of its own mRNA. Similar inhibition of translation of
      a reporter beta-galactosidase mRNA is observed when the adenine-rich auto
      regulatory sequence (ARS) is placed within the 5'-UTR of this mRNA. For this
      translational control the distance of the ARS from the 5' cap is not important.
      However, it determines the number of 40 S ribosomal subunits bound to the
      translationally arrested mRNA. Inhibition of mRNA translation by this regulatory
      sequence occurs at the step of joining of the 60 S ribosomal subunit to the pre
      initiation complex. Translational arrest of the ARS containing mRNA in a rabbit
      reticulocyte lysate cell-free system in the presence of exogenous Pabp1 protects
      the 5'-flanking region of the ARS from nuclease digestion. This protection
      depends on the binding of the 40 S ribosomal subunit to the mRNA. The size and
      the sequence of the nucleotide-protected fragment depends on the location of the
      ARS within the 5'-UTR. When the ARS is located at a distance of about 78
      nucleotides from the 5' cap, a 40-nucleotide long region adjacent to the ARS is
      protected. On the other hand, when the ARS is moved further away from the 5' cap
      to a distance of approximately 267 nucleotides, a 100-nucleotide-long region
      adjacent to the ARS is protected from nuclease digestion. Nuclease protection is
      attributed to the presence of one or more stalled 40 S ribosomal subunits near
      the Pabp1-bound ARS.

PMID- 11590160
TI  - Structure and function of the Escherichia coli RecE protein, a member of the RecB
      nuclease domain family.
AB  - The RecB subunit of the Escherichia coli RecBCD enzyme has both helicase and
      nuclease activities. The helicase function was localized to an N-terminal domain,
      whereas the nuclease activity was found in a C-terminal domain. Recent analysis
      has uncovered a group of proteins that have weak amino acid sequence similarity
      to the RecB nuclease domain and that are proposed to constitute a family of
      related proteins (Aravind, L., Walker, D. R., and Koonin, E. V. (1999) Nucleic
      Acids Res. 27, 1223-1242). One is the E. coli RecE protein (exonuclease VIII), an
      ATP-independent exonuclease that degrades the 5'-terminated strand of double
      stranded DNA. We have made mutations in several residues of RecE that align with
      the critical residues of RecB, and we find that the mutations reduce or abolish
      the nuclease activity of RecE but do not affect the enzyme binding to linear
      double-stranded DNA. Proteolysis experiments with subtilisin show that a stable
      34-kilodalton C-terminal domain that contains these critical residues has
      nuclease activity, whereas no stable proteolytic fragments accumulate from the N
      terminal portion of RecE. These results show that RecE has a nuclease domain and
      active site that are similar to RecB, despite the very weak sequence similarity
      between the two proteins. These similarities support the hypothesis that the
      nuclease domains of the two proteins are evolutionarily related.

PMID- 11590159
TI  - Protein associated with Myc (PAM) is a potent inhibitor of adenylyl cyclases.
AB  - Using the yeast two-hybrid assay and the second of the two large cytosolic
      domains of type V adenylyl cyclase (ACV) as bait, we identified a small region
      (amino acids 1028-1231) in the protein associated with Myc (PAM) as an
      interaction site for ACV. This small region of PAM as well as purified full
      length PAM inhibited the activity of ACV. Additionally, full-length PAM was a
      very potent inhibitor of ACI and AC activities in S49 cyc(-) cells and HeLa cells
      with IC(50) values in the pm and low nm range. Moreover, the regulator of
      chromatin condensation 1-like domain of PAM (amino acids 446-1062) was sufficient
      and as potent as full-length PAM at inhibiting the activity of ACV.
      Interestingly, full-length PAM did not inhibit ACII activity that was stimulated
      by either forskolin of Galpha(s). When endogenous levels of PAM in HeLa cells
      were decreased using antisense oligodeoxynucleotides, the basal cAMP content was
      elevated, and the dose-response curve for vasoactive intestinal peptide-elicited
      cAMP accumulation in HeLa cells was shifted to the left. Therefore, we conclude
      that PAM is a very potent, novel inhibitor of specific isoforms of AC.
      Furthermore, the regulator of chromatin condensation 1-like domain of PAM is
      sufficient to exert the effects of the full-length protein on AC and decreases in
      endogenous PAM levels in HeLa cells can modulate both basal and agonist
      stimulated cAMP accumulation.

PMID- 11590161
TI  - A protein G fragment from the salmonid viral hemorrhagic septicemia rhabdovirus
      induces cell-to-cell fusion and membrane phosphatidylserine translocation at low
      pH.
AB  - The fusion-related properties of segments p9, p3, p4, and p9 + p2 surrounding the
      p2 phospholipid-binding domain of the protein G (pG) of the salmonid rhabdovirus
      of viral hemorrhagic septicemia (VHS) (Nunez, E., Fernandez, A. M., Estepa, A.,
      Gonzalez-Ros, J. M., Gavilanes, F., and Coll, J. M. (1998) Virology 243, 322-330;
      Estepa, A., and Coll, J. M. (1996) Virology 216, 60-70), have been studied at
      neutral and fusion (low) pH values by using its derived peptides. Cell-to-cell
      fusion, translocation of phosphatidylserine, and inhibition of fusion of pG
      transfected cells defined the p9 + p2 (fragment 11, sequence 56-110) as a
      fragment with higher specific activity for anionic phospholipid aggregation than
      the previously reported p2. While fragment 11, p2, and p3 showed interactions
      with anionic phospholipids, p9 and p4 showed no interactions with any
      phospholipids. When added to a cell monolayer model at low pH, fragment 11
      induced pH-dependent cell-to-cell fusion and translocated phosphatidylserine from
      the inner to the outer leaflet of the membrane. At low pH and in the presence of
      anionic phospholipids, fragment 11 showed more than 80% beta-sheet conformation
      (IR and CD spectroscopies). Finally, anti-fragment 11 antibodies inhibited low pH
      dependent pG-transfected cell-to-cell fusion. All of the data support the
      conclusion that fragment 11 is a primary determinant of some of the viral cell
      fusion events in VHSV.

PMID- 11590162
TI  - Overexpression and mechanistic analysis of chromosomally encoded aminoglycoside
      2'-N-acetyltransferase (AAC(2')-Ic) from Mycobacterium tuberculosis.
AB  - The chromosomally encoded aminoglycoside N-acetyltransferase, AAC(2')-Ic, of
      Mycobacterium tuberculosis has a yet unidentified physiological function. The
      aac(2')-Ic gene was cloned and expressed in Escherichia coli, and AAC(2')-Ic was
      purified. Recombinant AAC(2')-Ic was a soluble protein of 20,000 Da and
      acetylated all aminoglycosides substrates tested in vitro, including
      therapeutically important antibiotics. Acetyl-CoA was the preferred acyl donor.
      The enzyme, in addition to acetylating aminoglycosides containing 2'-amino
      substituents, also acetylated kanamycin A and amikacin that contain a 2'-hydroxyl
      substituent, although with lower activity, indicating the capacity of the enzyme
      to perform both N-acetyl and O-acetyl transfer. The enzyme exhibited "substrate
      activation" with many aminoglycoside substrates while exhibiting Michaelis-Menten
      kinetics with others. Kinetic studies supported a random kinetic mechanism for
      AAC(2')-Ic. Comparison of the kinetic parameters of different aminoglycosides
      suggested that their hexopyranosyl residues and, to a lesser extent, the central
      aminocyclitol residue carry the major determinants of substrate affinity.

PMID- 11590163
TI  - Stabilization of partially folded conformation during alpha-synuclein
      oligomerization in both purified and cytosolic preparations.
AB  - Aggregation of alpha-synuclein is tightly associated with many neurodegenerative
      diseases, such as Parkinson's disease, dementia with Lewy body, Lewy body variant
      of Alzheimer's disease, multiple system atrophy, and Hallervorden-Spatz disease,
      implicating a crucial role of aggregated forms of alpha-synuclein in the
      pathogenesis. Here, we examined the effect of elevated temperature on the
      oligomerization and structural changes of alpha-synuclein in the early stage of
      aggregation and show that self-assembly is crucial for the stabilization of a
      partially folded conformation. The efficiency of alpha-synuclein oligomerization
      increased proportional to the temperature increase, both in purified form and in
      crude cytosolic preparation. This oligomerization coincided with a small but
      reproducible change in the circular dichroism spectrum and an increase in the 1
      anilinonaphthalene-8-sulfonic acid binding. The hydrodynamic dimensions of the
      dimer measured by size exclusion chromatography suggest a pre-molten globule-like
      structure. These data suggest that partially folded alpha-synuclein, which is
      unstable in the monomeric form, is stabilized by self-assembly and that these
      oligomers may evolve into the fibril nucleus.

PMID- 11590164
TI  - Structural basis for pterin antagonism in nitric-oxide synthase. Development of
      novel 4-oxo-pteridine antagonists of (6R)-5,6,7,8-tetrahydrobiopterin.
AB  - Pathological nitric oxide (NO) generation in sepsis, inflammation, and stroke may
      be therapeutically controlled by inhibiting NO synthases (NOS). Here we targeted
      the (6R)-5,6,7,8-tetrahydro-l-biopterin (H(4)Bip)-binding site of NOS, which,
      upon cofactor binding, maximally increases enzyme activity and NO production from
      substrate l-arginine. The first generation of H(4)Bip-based NOS inhibitors
      employed a 4-amino pharmacophore of H(4)Bip analogous to antifolates such as
      methotrexate. We developed a novel series of 4-oxo-pteridine derivatives that
      were screened for inhibition against neuronal NOS (NOS-I) and a structure
      activity relationship was determined. To understand the structural basis for
      pterin antagonism, selected derivatives were docked into the NOS pterin binding
      cavity. Using a reduced 4-oxo-pteridine scaffold, derivatives with certain
      modifications such as electron-rich aromatic phenyl or benzoyl groups at the 5-
      and 6-positions, were discovered to markedly inhibit NOS-I, possibly due to
      hydrophobic and electrostatic interactions with Phe(462) and Ser(104),
      respectively, within the pterin binding pocket. One of the most effective 4-oxo
      compounds and, for comparisons an active 4-amino derivative, were then co
      crystallized with the endothelial NOS (NOS-III) oxygenase domain and this
      structure solved to confirm the hypothetical binding modes. Collectively, these
      findings suggest (i) that, unlike the antifolate principle, the 4-amino
      substituent is not essential for developing pterin-based NOS inhibitors and (ii),
      provide a steric and electrostatic basis for their rational design.

PMID- 11590165
TI  - Cell-derived apolipoprotein E (ApoE) particles inhibit vascular cell adhesion
      molecule-1 (VCAM-1) expression in human endothelial cells.
AB  - Sub-endothelial infiltration of monocytes occurs early in atherogenesis and is
      facilitated by cell adhesion molecules that are up-regulated on activated
      endothelium. Apolipoprotein E (apoE) helps protect against atherosclerosis, in
      part, because apoE particles secreted by macrophages have local beneficial
      effects at lesion sites. Here, we hypothesize that such protection includes anti
      inflammatory actions and investigate whether cell-derived apoE can inhibit tumor
      necrosis factor-alpha-mediated up-regulation of vascular cell adhesion molecule-1
      (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Two models were used
      to mimic endothelial exposure to macrophage-derived apoE. In the first, HUVECs
      were transiently transfected to secrete apoE; VCAM-1 induction inversely
      correlated with secretion of apoE into the media (r = -0.76, p < 0.001). In the
      second, incubation of HUVECs with media from recombinant Chinese hamster ovary
      (CHO) cells expressing apoE (CHO(apoE)) also reduced VCAM-1 in a dose-dependent
      manner (r = -0.70, p < 0.001). Characterization of CHO(apoE) cell-derived apoE
      revealed several similarities to apoE particles secreted by human blood monocyte
      derived macrophages. The suppression of endothelial activation by apoE most
      likely occurs via stimulation of endothelial nitric oxide synthase; apoE
      increased levels of intracellular nitric oxide and its surrogate marker, cyclic
      guanosine monophosphate, while the nitric oxide synthase inhibitor, ethyl
      isothiourea, blocked its effect. We propose that apoE secreted locally at lesion
      sites by macrophages may be anti-inflammatory by stimulating endothelium to
      release NO and suppress VCAM-1 expression.

PMID- 11590166
TI  - The osteopontin-CD44 survival signal involves activation of the
      phosphatidylinositol 3-kinase/Akt signaling pathway.
AB  - We have recently demonstrated that the gene encoding the osteopontin (OPN)
      protein is activated both by interleukin-3 and granulocyte-macrophage colony
      stimulating factor signaling pathways and that, through binding to the cell
      surface receptor CD44, OPN contributes to the survival activities of interleukin
      (IL)-3 and GM-CSF (Lin, Y.-H., Huang, C.-J., Chao, J.-R., Chen, S.-T., Lee, S.
      F., Yen, J. J.-Y., and Yang-Yen, H.-F. (2000) Mol. Cell. Biol. 20, 2734-2742). In
      this report, we demonstrate that the CD44-binding domain of OPN involves a region
      containing amino acid residues from 121 to 140 and that both threonine and serine
      at positions 137 and 147, respectively, are essential for the survival
      stimulatory effect of OPN. Substitution of either residue with alanine results
      into a dominant negative mutant that overrides the survival effect of IL-3. Upon
      binding to the CD44 receptor, the wild-type OPN but not the inactive mutant
      induces activation of phosphatidylinositol 3-kinase and Akt. Last, we demonstrate
      that two waves of Akt activation are detected in IL-3-treated cells and that the
      survival promoting effect of OPN is mediated predominantly through the
      phosphatidylinositol 3-kinase/Akt signaling pathway. Together, our results
      suggest that a positive autoregulatory loop is involved in the survival pathway
      of IL-3.

PMID- 11590167
TI  - Peroxisome proliferator-activated receptor gamma inhibits transforming growth
      factor beta-induced connective tissue growth factor expression in human aortic
      smooth muscle cells by interfering with Smad3.
AB  - Activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) after
      balloon injury significantly inhibits VSMC proliferation and neointima formation.
      However, the precise mechanisms of this inhibition have not been determined. We
      hypothesized that activation of PPAR gamma in vascular injury could attenuate
      VSMC growth and matrix production during vascular lesion formation. Since
      connective tissue growth factor (CTGF) is a key factor regulating extracellular
      matrix production, abrogation of transforming growth factor beta (TGF-beta)
      induced CTGF production by PPAR gamma activation may be one of the mechanisms
      through which PPAR gamma agonists inhibit neointima formation after vascular
      injury. In this study, we demonstrate that the PPAR gamma natural ligand (15
      deoxyprostaglandin J(2)) and a synthetic ligand (GW7845) significantly inhibit
      TGF-beta-induced CTGF production in a dose-dependent manner in HASMCs. In
      addition, suppression of CTGF mRNA expression is relieved by pretreatment with an
      antagonist of PPAR gamma (GW9662), suggesting that the inhibition of CTGF
      expression is mediated by PPAR gamma. To elucidate further the molecular
      mechanism by which PPAR gamma inhibits CTGF expression, an approximately 2
      kilobase pair CTGF promoter was cloned. We found that PPAR gamma activation
      inhibits TGF-beta-induced CTGF promoter activity in a dose-dependent manner, and
      suppression of CTGF promoter activity by PPAR gamma activation is completely
      rescued by overexpression of Smad3, but not by Smad4. Furthermore, PPAR gamma
      physically interacts with Smad3 but not Smad4 in vitro in glutathione S
      transferase pull-down experiments. Taken together, the data suggest that PPAR
      gamma inhibits TGF-beta-induced CTGF expression in HASMCs by directly interfering
      with the Smad3 signaling pathway.

PMID- 11590168
TI  - Nitration and inactivation of tyrosine hydroxylase by peroxynitrite.
AB  - Tyrosine hydroxylase (TH) is modified by nitration after exposure of mice to 1
      methyl-4-phenyl-1,2,3,6-tetrahydrophenylpyridine. The temporal association of
      tyrosine nitration with inactivation of TH activity in vitro suggests that this
      covalent post-translational modification is responsible for the in vivo loss of
      TH function (Ara, J., Przedborski, S., Naini, A. B., Jackson-Lewis, V.,
      Trifiletti, R. R., Horwitz, J., and Ischiropoulos, H. (1998) Proc. Natl. Acad.
      Sci. U. S. A. 95, 7659-7663). Recent data showed that cysteine oxidation rather
      than tyrosine nitration is responsible for TH inactivation after peroxynitrite
      exposure in vitro (Kuhn, D. M., Aretha, C. W., and Geddes, T. J. (1999) J.
      Neurosci. 19, 10289-10294). However, re-examination of the reaction of
      peroxynitrite with purified TH failed to produce cysteine oxidation but resulted
      in a concentration-dependent increase in tyrosine nitration and inactivation.
      Cysteine oxidation is only observed after partial unfolding of the protein.
      Tyrosine residue 423 and to lesser extent tyrosine residues 428 and 432 are
      modified by nitration. Mutation of Tyr(423) to Phe resulted in decreased
      nitration as compared with wild type protein without loss of activity. Stopped
      flow experiments reveal a second order rate constant of (3.8 +/- 0.9) x 10(3) m(
      1) s(-1) at pH 7.4 and 25 degrees C for the reaction of peroxynitrite with TH.
      Collectively, the data indicate that peroxynitrite reacts with the metal center
      of the protein and results primarily in the nitration of tyrosine residue 423,
      which is responsible for the inactivation of TH.

PMID- 11590169
TI  - Integrin beta 1 signaling is necessary for transforming growth factor-beta
      activation of p38MAPK and epithelial plasticity.
AB  - Transforming growth factor-beta (TGF-beta) can induce epithelial to mesenchymal
      transdifferentiation (EMT) in mammary epithelial cells. TGF-beta-mediated EMT
      involves the stimulation of a number of signaling pathways by the sequential
      binding of the type II and type I serine/threonine kinase receptors,
      respectively. Integrins comprise a family of heterodimeric extracellular matrix
      receptors that mediate cell adhesion and intracellular signaling, hence making
      them crucial for EMT progression. In light of substantial evidence indicating TGF
      beta regulation of various beta(1) integrins and their extracellular matrix
      ligands, we examined the cross-talk between the TGF-beta and integrin signal
      transduction pathways. Using an inducible system for the expression of a
      cytoplasmically truncated dominant negative TGF-beta type II receptor, we blocked
      TGF-beta-mediated growth inhibition, transcriptional activation, and EMT
      progression. Dominant negative TGF-beta type II receptor expression inhibited TGF
      beta signaling to the SMAD and AKT pathways, but did not block TGF-beta-mediated
      p38MAPK activation. Interestingly, blocking integrin beta(1) function inhibited
      TGF-beta-mediated p38MAPK activation and EMT progression. Limiting p38MAPK
      activity through the expression of a dominant negative-p38MAPK also blocked TGF
      beta-mediated EMT. In summary, TGF-beta-mediated p38MAPK activation is dependent
      on functional integrin beta(1), and p38MAPK activity is required but is not
      sufficient to induce EMT.

PMID- 11590170
TI  - Binding of neuronal nitric-oxide synthase (nNOS) to carboxyl-terminal-binding
      protein (CtBP) changes the localization of CtBP from the nucleus to the cytosol:
      a novel function for targeting by the PDZ domain of nNOS.
AB  - Recent work suggests a role for PDZ domains in the targeting of binding partners
      to specific sites in the cell. To identify whether the PDZ domain of neuronal
      nitric-oxide synthase (nNOS) can play such a role, we performed affinity
      chromatography of brain extract with the nNOS PDZ domain. We identified the
      carboxyl-terminal-binding protein (CtBP), a phosphoprotein first identified as a
      binding partner to adenovirus E1A, as a nNOS binding partner. CtBP interacts with
      the PDZ domain of nNOS, and this interaction can be competed with peptide that
      binds to the PDZ peptide-binding site. In addition, binding of CtBP to nNOS is
      dependent on its carboxyl-terminal sequence -DXL, residues conserved between
      species that fit the canonical sequence for nNOS PDZ binding. Immunoprecipitation
      studies show that CtBP and nNOS associate in the brain. When CtBP is expressed in
      Madin-Darby canine kidney cells, its distribution is primarily nuclear; however,
      when CtBP is co-expressed with nNOS, its localization becomes more cytosolic.
      This change in CtBP localization does not occur when its carboxyl-terminal nNOS
      PDZ binding motif is mutated or when CtBP is co-expressed with postsynaptic
      density 95, another PDZ domain-containing protein. Taken together, our data
      suggest a new function for nNOS as a regulator of CtBP nuclear localization.

PMID- 11590171
TI  - Association of Na(+)-H(+) exchanger isoform NHE3 and dipeptidyl peptidase IV in
      the renal proximal tubule.
AB  - In an attempt to identify proteins that assemble with the apical membrane Na(+)
      H(+) exchanger isoform NHE3, we generated monoclonal antibodies (mAbs) against
      affinity-purified NHE3 protein complexes isolated from solubilized renal
      microvillus membrane vesicles. Hybridomas were selected based on their ability to
      immunoprecipitate NHE3. We have characterized in detail one of the mAbs (1D11)
      that specifically co-precipitated NHE3 but not villin or NaPi-2. Western blot
      analyses of microvillus membranes and immunoelectron microscopy of kidney
      sections showed that mAb 1D11 recognizes a 110-kDa protein highly expressed on
      the apical membrane of proximal tubule cells. Immunoaffinity chromatography was
      used to isolate the antigen against which mAb 1D11 is directed. N-terminal
      sequencing of the purified protein identified it as dipeptidyl peptidase IV
      (DPPIV) (EC ), which was confirmed by assays of DPPIV enzyme activity. We also
      evaluated the distribution of the NHE3-DPPIV complex in microdomains of rabbit
      renal brush border. In contrast to the previously described NHE3-megalin complex,
      which principally resides in a dense membrane population (coated pits) in which
      NHE3 is inactive, the NHE3-DPPIV complex was predominantly in the microvillar
      fraction in which NHE3 is active. Serial precipitation experiments confirmed that
      anti-megalin and anti-DPPIV antibodies co-precipitate different pools of NHE3.
      Taken together, these studies revealed an unexpected association of the brush
      border Na(+)-H(+) exchanger NHE3 with dipeptidyl peptidase IV in the proximal
      tubule. These findings raise the possibility that association with DPPIV may
      affect NHE3 surface expression and/or activity.

PMID- 11590172
TI  - A partially structured species of beta 2-microglobulin is significantly populated
      under physiological conditions and involved in fibrillogenesis.
AB  - The folding of beta(2)-microglobulin (beta(2)-m), the protein forming amyloid
      deposits in dialysis-related amyloidosis, involves formation of a partially
      folded conformation named I(2), which slowly converts into the native fold, N.
      Here we show that the partially folded species I(2) can be separated from N by
      capillary electrophoresis. Data obtained with this technique and analysis of
      kinetic data obtained with intrinsic fluorescence indicate that the I(2)
      conformation is populated to approximately 14 +/- 8% at equilibrium under
      conditions of pH and temperature close to physiological. In the presence of
      fibrils extracted from patients, the I(2) conformer has a 5-fold higher
      propensity to aggregate than N, as indicated by the thioflavine T test and light
      scattering measurements. A mechanism of aggregation of beta(2)-m in vivo
      involving the association of the preformed fibrils with the fraction of I(2)
      existing at equilibrium is proposed from these results. The possibility of
      isolating and quantifying a partially folded conformer of beta(2)-m involved in
      the amyloidogenesis process provides new opportunities to monitor hemodialytic
      procedures aimed at the reduction of such species from the pool of circulating
      beta(2)-m but also to design new pharmaceutical approaches that consider such
      species as a putative molecular target.

PMID- 11590173
TI  - Differing ADP release rates from myosin heavy chain isoforms define the
      shortening velocity of skeletal muscle fibers.
AB  - To understand mammalian skeletal myosin isoform diversity, pure myosin isoforms
      of the four major skeletal muscle myosin types (myosin heavy chains I, IIA, IIX,
      and IIB) were extracted from single rat muscle fibers. The extracted myosin (1-2
      microg/15-mm length) was sufficient to define the actomyosin dissociation
      reaction in flash photolysis using caged-ATP (Weiss, S., Chizhov, I., and Geeves,
      M. A. (2000) J. Muscle Res. Cell Motil. 21, 423-432). The ADP inhibition of the
      dissociation reaction was also studied to give the ADP affinity for actomyosin
      (K(AD)). The apparent second order rate constant of actomyosin dissociation gets
      faster (K(1)k(+2) = 0.17 -0.26 microm(-1) x s(-1)), whereas the affinity for ADP
      is weakened (250-930 microm) in the isoform order I, IIA, IIX, IIB. Both sets of
      values correlate well with the measured maximum shortening velocity (V(0)) of the
      parent fibers. If the value of K(AD) is controlled largely by the rate constant
      of ADP release (k(-AD)), then the estimated value of k(-AD) is sufficiently low
      to limit V(0). In contrast, [ATP]K(1)k(+2) at a physiological concentration of 5
      mm ATP would be 2.5-6 times faster than k(-AD).

PMID- 11590174
TI  - Microarray analysis detects novel Pax3 downstream target genes.
AB  - Pax3 is a transcription factor that is required for the development of embryonic
      neural tube, neural crest, and somatic derivatives. Our previous study (Mayanil,
      C. S. K., George, D., Mania-Farnell, B., Bremer, C. L., McLone, D. G., and
      Bremer, E. G. (2000) J. Biol. Chem. 275, 23259-23266) reveals that overexpression
      of Pax3 in a human medulloblastoma cell line, DAOY, resulted in an up-regulation
      in alpha-2,8-polysialyltransferase (STX) gene expression and an increase in
      polysialic acid on neural cell adhesion molecule. This finding suggests that STX
      might be a previously undescribed downstream target of Pax3. Because Pax3 is
      important in diverse cellular functions during development, we are interested in
      the identification of additional downstream targets of Pax3. We utilized
      oligonucleotide arrays and RNA isolated from stable Pax3 transfectants to
      identify potential target genes. A total of 270 genes were altered in the Pax3
      transfectants as compared with the vector control and parental cell line. An
      independent analysis by cDNA expression array and real-time quantitative
      polymerase chain reaction of several genes confirmed the changes observed by the
      oligonucleotide microarray data. Of the genes that displayed significant changes
      in expression, several contain paired and homeodomain binding motifs of Pax3 in
      their promoter regions. Using promoter-luciferase reporter transfection assays
      and electromobility shift assays, we showed at least one previously undescribed
      downstream target, STX, to be a biological downstream target of Pax3. Thus we
      report several previously undescribed candidate genes to be potential downstream
      targets of Pax3.

PMID- 11590175
TI  - Polyamine depletion induces rapid NF-kappa B activation in IEC-6 cells.
AB  - The proliferation of the rat intestinal mucosal IEC-6 cell line requires
      polyamines, whose synthesis is catalyzed by the enzyme ornithine decarboxylase
      (ODC). ODC inhibition leads to polyamine depletion, as well as inhibition of both
      cell proliferation and apoptosis by regulating gene expression. The NF-kappa B
      transcription factor regulates genes involved in apoptotic, immune, and
      inflammatory responses. In the present study we tested the hypothesis that NF
      kappa B is activated following ODC inhibition. We found that the inhibition of
      ODC by alpha-difluoromethylornithine (DFMO) resulted in a approximately 50%
      decrease in intracellular putrescine levels within 1 h. NF-kappa B is activated
      by DFMO through the degradation of the inhibitory protein I kappa B alpha that
      sequesters NF-kappa B in the cytoplasm. The DFMO-induced NF-kappa B complexes
      contain the p65 and p50 members of the Rel protein family. DFMO-induced NF-kappa
      B activation was accompanied by the translocation of p65 from the cytoplasm into
      the nucleus. DFMO selectively inhibited a gene reporter construct dependent on
      the kappa B site present in the HLA-B7 gene. In contrast, DFMO had no effect on a
      gene reporter construct dependent on the kappa B site present in the interleukin
      8 gene. Thus, we report that ODC inhibition activates the NF-kappa B
      transcription factor, which may mediate the altered physiological state of
      intestinal cells that occurs following polyamine depletion.

PMID- 11590176
TI  - Two different targeting signals direct human peroxisomal membrane protein 22 to
      peroxisomes.
AB  - The 22-kDa peroxisomal membrane protein (PMP22) is a major component of
      peroxisomal membranes in mammals. Although its precise role in peroxisome
      function is poorly understood, it seems to be involved in pore forming activity
      and may contribute to the unspecific permeability of the organelle membrane.
      PMP22 is synthesized on free cytosolic ribosomes and then directed to the
      peroxisome membrane by specific targeting information. Previous studies in rats
      revealed that PMP22 contains one distinct peroxisomal membrane targeting signal
      in the amino-terminal cytoplasmic tail. We cloned and characterized the targeting
      signal of human PMP22 and compared it with the already described characteristics
      of the corresponding rat protein. Amino acid sequence alignment of rat and human
      protein revealed 77% identity including a high conservation of several protein
      motifs. We expressed various deletion constructs of PMP22 in fusion with the
      green fluorescent protein in COS-7 cells and determined their intracellular
      localization. In contrast to previous studies on rat PMP22 and most other
      peroxisomal membrane proteins, we showed that human as well as rat PMP22 contains
      two distinct and nonoverlapping peroxisomal membrane targeting signals, one in
      the amino-terminal and the other in the carboxyl-terminal protein region. They
      consist of two transmembrane domains and adjacent protein loops with almost
      identical basic clusters. Both of these peroxisomal targeting regions interact
      with PEX19, a factor required for peroxisome membrane synthesis. In addition, we
      observed that fusing the green fluorescent protein immediately adjacent to the
      targeting region completely abolishes targeting function and mislocalizes PMP22
      to the cytosol.

PMID- 11590177
TI  - Thrombin stimulation of the vascular cell adhesion molecule-1 promoter in
      endothelial cells is mediated by tandem nuclear factor-kappa B and GATA motifs.
AB  - The goal of this study was to delineate the transcriptional mechanisms underlying
      thrombin-mediated induction of vascular adhesion molecule-1 (VCAM-1). Treatment
      of human umbilical vein endothelial cells with thrombin resulted in a 3.3-fold
      increase in VCAM-1 promoter activity. The upstream promoter region of VCAM-1
      contains a thrombin response element, two nuclear factor kappaB (NF-kappaB)
      motifs, and a tandem GATA motif. In transient transfection assays, mutation of
      the thrombin response element had no effect on thrombin induction. In contrast,
      mutation of either NF-kappaB site resulted in a complete loss of induction,
      whereas a mutation of the two GATA motifs resulted in a significant reduction in
      thrombin stimulation. In electrophoretic mobility shift assays, nuclear extracts
      from thrombin-treated endothelial cells displayed markedly increased binding to
      the tandem NF-kappaB and GATA motifs. The NF-kappaB complex was supershifted with
      anti-p65 antibodies, but not with antibodies to RelB, c-Rel, p50, or p52. The
      GATA complex was supershifted with antibodies to GATA-2, but not GATA-3 or GATA
      6. A construct containing tandem copies of the VCAM-1 GATA motifs linked to a
      minimal thymidine kinase promoter was induced 2.4-fold by thrombin. Taken
      together, these results suggest that thrombin stimulation of VCAM-1 in
      endothelial cells is mediated by the coordinate action of NF-kappaB and GATA
      transcription factors.

PMID- 11590178
TI  - Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that
      promotes hepatocyte growth factor/scatter factor mitogenic activity.
AB  - Proteoglycans that modulate the activities of growth factors, chemokines, and
      coagulation factors regulate in turn the vascular endothelium with respect to
      processes such as inflammation, hemostasis, and angiogenesis. Endothelial cell
      specific molecule-1 is mainly expressed by endothelial cells and regulated by pro
      inflammatory cytokines (Lassalle, P., Molet, S., Janin, A., Heyden, J. V.,
      Tavernier, J., Fiers, W., Devos, R., and Tonnel, A. B. (1996) J. Biol. Chem. 271,
      20458-20464). We demonstrate that this molecule is secreted as a soluble dermatan
      sulfate (DS) proteoglycan. This proteoglycan represents the major form either
      secreted by cell lines or circulating in the human bloodstream. Because this
      proteoglycan is specifically secreted by endothelial cells, we propose to name it
      endocan. The glycosaminoglycan component of endocan consists of a single DS chain
      covalently attached to serine 137. Endocan dose-dependently increased the
      hepatocyte growth factor/scatter factor (HGF/SF)-mediated proliferation of human
      embryonic kidney cells, whereas the nonglycanated form of endocan did not.
      Moreover, DS chains purified from endocan mimicked the endocan-mediated increase
      of cell proliferation in the presence of HGF/SF. Overall, our results demonstrate
      that endocan is a novel soluble dermatan sulfate proteoglycan produced by
      endothelial cells. Endocan regulates HGF/SF-mediated mitogenic activity and may
      support the function of HGF/SF not only in embryogenesis and tissue repair after
      injury but also in tumor progression.

PMID- 11590180
TI  - ATP synthase F(1) sector rotation. Defective torque generation in the beta
      subunit Ser-174 to Phe mutant and its suppression by second mutations.
AB  - Subunit gamma of the ATP synthase F(1) sector is located at the center of the
      alpha(3)beta(3) hexamer and rotates unidirectionally during ATP hydrolysis,
      generating the rotational torque of approximately 45 pN.nm. A mutant F(1) with
      the betaSer-174 to Phe substitution (betaS174F) in the beta subunit generated
      lower torque ( approximately 17 pN.nm), indicating that betaS174F is mechanically
      defective, the first such mutant reported. The defective rotation of betaS174F
      was suppressed by a second-site mutation, betaGly-149 to Ala, betaIle-163 to Ala,
      or betaIle-166 to Ala in the same subunit, but not by betaLeu-238 to Ala. These
      results suggest that the region between betaGly-149 and betaSer-174 plays an
      important role in the coupling between ATP hydrolysis and mechanical work.

PMID- 11590179
TI  - The trophinin gene encodes a novel group of MAGE proteins, magphinins, and
      regulates cell proliferation during gametogenesis in the mouse.
AB  - Trophinin is a membrane protein that mediates apical cell adhesion between
      trophoblastic cells and luminal epithelial cells of the endometrium and is
      implicated in the initial attachment during the process of human embryo
      implantation. The present study identified novel trophinin gene transcripts,
      which encode proteins structurally distinct from trophinin protein in the mouse.
      We designated these proteins "magphinins," because they share consensus amino
      acid sequences with MAGE (melanoma-associated antigen) superfamily proteins.
      Among many MAGE proteins, magphinins are closely related to NRAGE, which mediates
      p75 neurotrophin receptor-dependent apoptosis, and necdin, which is a strong
      suppressor of cell proliferation in post-mitotic neurons. There are three major
      forms of magphinins, i.e. magphinin-alpha, -beta, and -gamma, in the mouse, which
      are formed due to alternative usage of different exons. Northern blot analysis
      revealed that magphinins are expressed in brain, ovary, testis, and epididymis.
      In addition, Western blot analysis and in vitro translation experiments showed
      that magphinins expressed in the mouse ovary and testis are translation products
      utilizing the second initiation AUG codon and contain an active nuclear
      localization signal. Ectopic expression of magphinins in mammalian cells resulted
      in nuclear localization of magphinin and suppressed cell proliferation.
      Immunohistochemistry of the mouse ovary and testis showed that magphinin proteins
      are distributed in the cytoplasm of the male and female germ cells, whereas these
      proteins are translocated to the nucleus at a specific stage of gametogenesis.
      These results strongly suggest that magphinins regulate cell proliferation during
      gametogenesis in the mouse.

PMID- 11590181
TI  - Identification and characterization of a novel Golgi protein, GCP60, that
      interacts with the integral membrane protein giantin.
AB  - We demonstrated previously that the integral membrane protein giantin has the
      Golgi localization signal at the COOH-terminal cytoplasmic domain (Misumi, Y.,
      Sohda, M., Tashiro, A., Sato, H., and Ikehara, Y. (2001) J. Biol. Chem. 276, 6867
      6873). In the present study, using this domain as bait in the yeast two-hybrid
      screening system, we identified a novel protein interacting with giantin. The 3.6
      kilobase mRNA encoding a 528-amino acid protein of 60 kDa designated GCP60 was
      ubiquitously expressed and was especially abundant in the testis and ovary.
      Immunofluorescence and immunoelectron microscopy confirmed that GCP60 was co
      localized with giantin in the Golgi complex. GCP60 was found to be a peripheral
      protein associated with the Golgi membrane, where a COOH-terminal domain of GCP60
      interacts with the COOH-terminal cytoplasmic domain of giantin. Overexpression of
      the COOH-terminal domain of GCP60 caused disassembly of the Golgi structure and
      blocked protein transport from the endoplasmic reticulum to the Golgi. Taken
      together, these results suggest that GCP60 is involved in the maintenance of the
      Golgi structure by interacting with giantin, affecting protein transport between
      the endoplasmic reticulum and the Golgi.

PMID- 11590182
TI  - The role of hepatic nuclear factor 1 alpha and PDX-1 in transcriptional
      regulation of the pdx-1 gene.
AB  - The PDX-1 homeodomain transcription factor regulates pancreatic development and
      adult islet beta cell function. Expression of the pdx-1 gene is almost
      exclusively localized to beta cells within the adult endocrine pancreas. Islet
      beta cell-selective transcription is controlled by evolutionarily conserved
      subdomain sequences (termed Areas I (-2839 to -2520 base pairs (bp)), II (-2252
      to -2023 bp), and III (-1939 to -1664 bp)) found within the 5'-flanking region of
      the pdx-1 gene. Areas I and II are independently capable of directing beta cell
      selective reporter gene activity in transfection assays, with Area I-mediated
      stimulation dependent upon binding of hepatic nuclear factor 3 beta (HNF3 beta),
      a key regulator of islet beta cell function. To identify other transactivators of
      Area I, highly conserved sequence segments within this subdomain were
      mutagenized, and their effect on activation was determined. Several of the
      sensitive sites were found by transcription factor data base analysis to
      potentially bind endodermally expressed transcription factors, including HNF1
      alpha (-2758 to -2746 bp, Segment 2), HNF4 (-2742 to -2730 bp, Segment 4; -2683
      to -2671 bp, Segment 7-8), and HNF6 (-2727 to -2715 bp, Segment 5). HNF1 alpha,
      but not HNF4 and HNF6, binds specifically to Area I sequences in vitro. HNF1
      alpha was also shown to specifically activate Area I-driven transcription through
      Segment 2. In addition, PDX-1 itself was found to stimulate Area I activation.
      The chromatin immunoprecipitation assay performed with PDX-1 antisera also
      demonstrated that this factor bound to Area I within the endogenous pdx-1 gene in
      beta cells. Our results indicate that regulatory factors binding to Area I
      conserved sequences contribute to the selective transcription pattern of the pdx
      1 gene and that control is mediated by endodermal regulators like HNF1 alpha,
      HNF3 beta, and PDX-1.

PMID- 11590183
TI  - Proinflammatory activity of glycosylphosphatidylinositol anchors derived from
      Trypanosoma cruzi: structural and functional analyses.
AB  - A strong activation of macrophages is observed during acute infection with
      Trypanosoma cruzi. Little is known, however, about the parasite molecules that
      are responsible for this early activation of innate immunity. Recent studies have
      shown the stimulatory activity of protozoan-derived glycosylphosphatidylinositol
      (GPI) anchors on cultured macrophages. In this review, we provide a detailed
      analysis of the correlation between structure and proinflammatory activity by T.
      cruzi-derived GPI anchors. We also cover the studies that have identified the
      Toll-like receptor 2 as a functional GPI receptor and have partially
      characterized signaling pathways triggered by T. cruzi-derived GPI anchors, which
      lead to the synthesis of proinflammatory cytokines in macrophages. Finally, we
      discuss the implications of these findings in resistance and pathogenesis during
      the infection with T. cruzi.

PMID- 11590184
TI  - Microenvironmental influence on macrophage regulation of angiogenesis in wounds
      and malignant tumors.
AB  - Angiogenesis is the development of blood vessels from an existing vasculature.
      This process is fundamental to both physiological wound healing and the growth of
      malignant tumors, as it restores or creates a blood supply to growing tissue. In
      both cases, the release of angiogenic molecules by macrophages recruited to the
      wound or tumor site is central to the formation of these neovessels. Reduced
      vascular perfusion in tissues generates tissue ischemia and a marked reduction in
      local levels of oxygen (hypoxia) and glucose. Cells adapt by switching to
      anaerobic metabolic pathways, with a concomitant increase in lactate production
      and reduction in extracellular pH. In tumors, these microenvironmental "stress"
      factors stimulate tumor cells to secrete a wide array of proangiogenic cytokines
      and enzymes, promoting the re-establishment of a local vascular supply. Here we
      review the evidence that these stress factors, in particular hypoxia and high
      lactate levels, stimulate macrophages to perform similar proangiogenic functions
      in both tumors and wounds. The resolution of wounds results in restoration of
      tissue integrity and perfusion, and macrophage presence is reduced to preinjury
      levels. However, in tumors a high number of macrophages persists and might
      contribute to the ongoing growth, neovascularization, and metastasis of malignant
      cells.

PMID- 11590185
TI  - Amoeboid leukocyte crawling through extracellular matrix: lessons from the
      Dictyostelium paradigm of cell movement.
AB  - Cell movement within three-dimensional tissues is a cycling multistep process
      that requires the integration of complex biochemical and biophysical cell
      functions. Different cells solve this challenge differently, which leads to
      differences in migration strategies. Migration principles established for
      leukocytes share many characteristics with those described for ameba of the lower
      eukaryote Dictyostelium discoideum. The hallmarks of amoeboid movement include a
      simple polarized shape, dynamic pseudopod protrusion and retraction, flexible
      oscillatory shape changes, and rapid low-affinity crawling. Amoeboid crawling
      includes haptokinetic adhesion-dependent as well as biophysical migration
      mechanisms on or within many structurally and functionally different substrates.
      We describe central aspects of amoeboid movement in leukocytes and the
      implications for leukocyte crawling and positioning strategies within
      interstitial tissues.

PMID- 11590186
TI  - Leukocytes infiltrating the pancreatic islets of nonobese diabetic mice are
      transformed into inactive exiles by combinational anti-cell adhesion therapy.
AB  - Leukocytes infiltrate the pancreatic islets of nonobese diabetic mice, causing
      beta-cell destruction and autoimmune Type I diabetes. Here, we completely blocked
      adoptive transfer of diabetes and reduced spontaneous disease incidence from 71%
      to 17% by simultaneously administering a combination of antibodies directed
      against alpha4, beta2, and beta7 integrins and their ligands VCAM-1, MAdCAM-1,
      and ICAM-1 for 52 and 28 days, respectively. CD4 and CD8 T cells and macrophages
      were excluded from islets and remained entrapped in a peri-islet location as
      inactive exiles, no longer expressing normal levels of interferon-gamma,
      interleukin-4, and iNOS. Only IL-10 expression was retained, which could aid
      immunosuppression. Infiltrating leukocytes retained a peri-islet location, even
      215 days following suspension of antibody treatment, potentially forming a
      barrier to the entry of active, autoantigen-reactive T cells. Combination
      treatment was effective against spontaneous disease when administered from 7 days
      of age but ineffective when initiated late in the prediabetic period (day 40 or
      70). Nevertheless, anti-alpha4 subunit mAb monotherapy alone was very effective,
      reducing insulitis to levels similar to those obtained with combinational
      antibody treatment, suggesting that alpha4 integrins are major receptors
      contributing to leukocyte infiltration. Treatment with anti-alpha4 integrin
      antibody retained some therapeutic benefit when administered from days 7, 40, or
      70 of age. The results have implications for the treatment of diabetes and
      provide a unique insight into the fate of disease-forming leukocytes following
      anti-CAM therapy.

PMID- 11590187
TI  - Vdelta1 and Vdelta2 gammadelta T cells express distinct surface markers and might
      be developmentally distinct lineages.
AB  - We report here that the two major types of gammadelta T cells found in human
      blood, Vdelta1 and Vdelta2, were found to have markedly different phenotypes.
      Vdelta2 cells had a phenotype typical of most alphabeta T cells in blood; i.e.,
      they were CD5(+), CD28(+), and CD57(-). In contrast, Vdelta1 cells tended to be
      CD5(-/dull), CD28(-), and CD57(+). Furthermore, although Vdelta1 T cells appeared
      to be "naive" in that they were CD45RA(+), they were CD62L(-) and on stimulation
      uniformly produced interferon-gamma, indicating that they are in fact
      memory/effector cells. This phenotype for Vdelta1 cells was similar to that of
      intestinal intraepithelial lymphocytes, a subset that can develop in the absence
      of the thymus. We suggest that the Vdelta1 and Vdelta2 T cell subsets represent
      distinct lineages with different developmental pathways. The disruption of the
      supply of normal, thymus-derived T cells in HIV-infected individuals might be
      responsible for the shift in the Vdelta2/Vdelta1 ratio that occurs in the blood
      of individuals with HIV disease.

PMID- 11590188
TI  - Morphine modulates lymph node-derived T lymphocyte function: role of caspase-3, 
      8, and nitric oxide.
AB  - The major objective of this paper is to characterize the mechanism by which
      morphine modulates lymphocyte function and if these effects are mediated through
      the mu-opioid receptor. We evaluated the in vitro effects of morphine on
      lymphocytes that were freshly isolated from lymph nodes from wild type (WT) and
      mu-opioid receptor knock-out (MORKO) mice. Results show that morphine inhibits
      Con A-induced lymph node T-cell proliferation and IL-2 and IFN-gamma synthesis in
      a dose-dependent manner. This effect was abolished in lymph node cells isolated
      from MORKO mice. The inhibition of T-cell function with low-dose morphine was
      associated with an increase in caspase-3- and caspase-8-mediated apoptosis. The
      inhibition of T-cell function with high-dose morphine was associated with an
      increase in the inducible NO synthase mRNA expression. N(G)-nitro-L-arginine
      methyl ester (L-NAME) antagonized the apoptosis induced by high-dose morphine.
      Our results suggest that low-dose morphine, through the mu-opioid receptor, can
      induce lymph node lymphocyte apoptosis through the cleavage activity of caspase-3
      and caspase-8. Morphine at high doses induces NO release. This effect of morphine
      is also mediated through the mu-opioid receptor present on the surface of
      macrophages.

PMID- 11590189
TI  - Inhibition of antibody-dependent stimulation of lipoteichoic acid-treated human
      monocytes and macrophages by polyglycerolphosphate-reactive peptides.
AB  - By itself, lipoteichoic acid (LTA) obtained from S. pyogenes, S. aureus, or E.
      hirae poorly stimulated cytokine production by macrophages, whereas in the
      presence of anti-polyglycerol phosphate (PGP), the cells secreted significant
      amounts of IL-6. Two peptides constructed from the deduced sequence of the
      selected anti-PGP phage-antibody's complementary-determining region 3 of the
      variable heavy chain (V(H)-CDR3) reacted specifically with PGP. The monomeric
      form of the peptides markedly inhibited cytokine production by macrophages
      pretreated with LTA and anti-LTA. In contrast, the polyvalent form of
      biotinylated peptides complex with streptavidin-induced cytokine production by
      the LTA-treated macrophages. The data taken together support the concept that
      cross-linking of macrophage-bound LTA by anti-PGP is required for cytokine
      release by these cells. Importantly, these studies identified small, PGP-reactive
      peptides as potential tools in reducing this proinflammatory process.

PMID- 11590190
TI  - Identification and comparison of residues critical for cell-adhesion activities
      of two neutrophil CD66 antigens, CEACAM6 and CEACAM8.
AB  - CEACAM6 (CD66c) and CEACAM8 (CD66b) are cell-adhesion proteins on neutrophils
      that belong to the human carcinoembryonic antigen (CEA) family. CEACAM6 reveals
      homophilic adhesion and heterophilic adhesion to other CEACAM family antigens
      including CEACAM8, CEACAM1, and CEA, whereas CEACAM8 exhibits only heterophilic
      adhesion to CEACAM6. Here, we investigated and compared structural requirements
      for the homophilic adhesion of CEACAM6 and heterophilic adhesion between CEACAM6
      and CEACAM8 at the amino acid level by using CHO transfectants expressing their
      mutant and chimeric proteins. The NH(2)-terminal domain (N-domain) of CEACAM6
      expressed on a CHO cell was suggested to bind the N-domain of CEACAM6 or CEACAM8
      on the opposing cell. By homologue-scanning mutagenesis, we found that the
      locations of the sequences critical for the adhesion of CEACAM6 to itself and to
      CEACAM8 are overlapped and that they are highly similar but not identical to the
      locations of the residues previously shown to be essential for the binding of
      CEACAM antigens to Opa proteins of pathogenic NEISSERIAE: Our findings imply that
      subtle differences in the N-domain sequences determine the specificity of the
      CEACAM antigens on neutrophils for interaction with the same or different CEACAM
      antigens and the bacterial proteins.

PMID- 11590191
TI  - Crotalus durissus terrificus snake venom regulates macrophage metabolism and
      function.
AB  - In the present study, we examined the effect of Crotalus durissus terrificus
      venom on rat macrophage metabolism and function. Two hours after subcutaneous
      injection of the venom, peritoneal resident (unstimulated), elicited
      (thioglycollate-stimulated), and activated Mycobacterium bovis strain bacille
      Calmette Guerin (BCG) macrophages were collected, and their functional and
      metabolic parameters were analyzed. The venom inhibited spreading and
      phagocytosis of macrophages. On the other hand, this treatment increased H(2)O(2)
      and NO production, candidacidal activity, and the activities of key enzymes of
      glycolysis and glutaminolysis. We also investigated whether the venom could
      affect macrophage activation by thioglycollate or BCG. The administration of
      venom 2 h before injection of thioglycollate and BCG or 2 or 3 days after
      injection of the thioglycollate or BCG, respectively, did not modify the previous
      observations. These findings suggest that crotalic venom leads the macrophage to
      an activated state, with high production of oxygen- and nitrogen-reactive
      species. This cell activation state does not include inflammatory properties of
      spreading and phagocytosis.

PMID- 11590192
TI  - Effects of intracellular zinc depletion on metallothionein and ZIP2 transporter
      expression and apoptosis.
AB  - Zinc is critical for the functional and structural integrity of cells. We have
      used the monocytic cell line THP-1 as a model in which to study both the
      responsiveness of metallothionein and ZIP2 transporter expression to zinc
      depletion induced by the intracellular zinc chelator TPEN [N,N,N',N'-tetrakis(2
      pyridylmethyl) ethylenediamine] and the extent of concomitant apoptosis.
      Metallothionein expression increased proportionately with the addition of zinc to
      the medium and decreased with TPEN treatment. When treated with TPEN, both THP-1
      cells and human peripheral blood mononuclear cells exhibited marked decreases in
      cellular zinc concentrations and increases in ZIP2 mRNA expression. These results
      suggest that cells attempt to homeostatically adjust to zinc depletion. When THP
      1 cells were treated with >5 microM TPEN, cell viability decreased, and cells
      entered the early stages of apoptosis. These data show that metallothionein and
      ZIP2 expression are inversely related during zinc depletion and that apoptosis is
      concurrent with these changes.

PMID- 11590193
TI  - Membrane trafficking of CD1c on activated T cells.
AB  - We investigated the regulation of and the intracellular trafficking involved in
      the membrane expression of CD1c antigen on activated mature T cells. Membrane
      expression of this glycoprotein was highly regulated and dependent on the
      activation state of the cells. The presence of the CD1c antigen on activated
      peripheral blood mononuclear cells (PBMCs) was confirmed by flow cytometry,
      reverse transcriptase-PCR (RT-PCR), and immunoperoxidase staining. The RT-PCR
      analysis of the alpha3- and 3'-untranslated regions of CD1C showed that
      phytohemagglutinin (PHA) activation induced expression of transcripts that encode
      the three isoforms (soluble, membrane, and cytoplasmic/soluble).
      Immunocytochemical studies showed a specific association of CD1c with the cell
      membrane and a cytoplasmic, perinuclear distribution. Although flow-cytometric
      staining confirmed the intracellular presence of CD1c, membrane expression on PHA
      blast cells was not detected. We found that membrane detection of CD1c antigen
      was temperature dependent. Cell surface binding of the anti-CD1c monoclonal
      antibody (mAb) was consistently negative at 4 and 37 degrees C but was detected
      at room temperature (18-22 degrees C). At physiologic temperatures, activated
      PBMCs showed intracellular accumulation of the anti-CD1c mAbs, indicating that
      CD1c cycled between cell surface and intracellular compartments. The CD1c
      exocytosis pathway was sensitive to Brefeldin A, cytochalasin B, and chloroquine.

PMID- 11590194
TI  - Spontaneous formation of germinal centers in autoimmune mice.
AB  - The mechanisms of autoantibody production are not well understood. Germinal
      centers (GC) may be important sites of immune disregulation in autoimmune
      diseases. In this study, we document the presence of spontaneous GC formation in
      the spleens of several autoimmune mouse strains that spontaneously develop
      autoimmune Type I diabetes and a lupus-like disease. In contrast, mouse strains
      that do not develop lupus did not exhibit spontaneous formation of GC. In all of
      the autoimmune strains studied, GC were present at 1-2 months of age, a time that
      closely parallels the appearance of autoantibodies. Like the GC that develop
      after purposeful immunization, GC in autoimmune mice contained B220(+), PNA(+),
      and GL-7(+) B cells, and FDC-M1(+) follicular dendritic cells. In addition,
      spontaneously formed GC in autoimmunity and those caused by immunization were
      abrogated in a similar way by a short-term treatment with anti-CD40 ligand
      antibody. These data indicate that spontaneously forming GC in autoimmunity are
      similar to those appearing after purposeful immunization.

PMID- 11590195
TI  - Leukocyte elastase in murine and human non-Hodgkin lymphomas.
AB  - Extracellular proteases play a crucial role in the invasive behavior of normal
      and transformed leukocytes. Thus far, however, most of the attention has been
      focused on members of the family of matrix metalloproteinases. In this work, we
      show that lymphoma cells can express leukocyte elastase (LE) and recruit the
      enzyme at their surface via ICAM-1. The expression of LE by lymphoma cells was
      augmented significantly by stimulation with IL-6 and IL-13, both of which also
      induced the expression of MMP-9. Although LE and IL-13 transcripts were detected
      in several non-Hodgkin's lymphomas, immunohistochemical analysis of lymphoma
      tissues also showed that LE was strongly expressed in infiltrating leukocytes.
      Given the spectrum of key molecules that can be cleaved by LE and that LE and MMP
      9 are involved in the invasive behavior of normal or transformed leukocytes, our
      results raise the hypothesis that LE plays a crucial role in the multistep
      processes of inflammation and lymphoma metastasis.

PMID- 11590196
TI  - A defect in HIV-1 transgenic murine macrophages results in deficient nitric oxide
      production.
AB  - HIV transgenic mice bearing multiple copies of a noninfectious (Deltagag/pol)
      proviral DNA were tested for the systemic production of nitric oxide (NO). Serum
      levels of NO metabolites were reduced about 50% in HIV transgenic mice compared
      with nontransgenic sibling mice. This difference persisted when NO production was
      induced with peritoneal injections of bacterial endotoxin (LPS). Peritoneal
      inflammatory macrophages, but not resident peritoneal macrophages, derived from
      HIV-1 transgenic mice and activated in vitro with LPS and IFN-gamma (or tumor
      necrosis factor alpha and IFN-gamma) also produced about 50% less NO than did
      macrophages harvested from nontransgenic littermates. Isogenic, transgenic mice
      bearing mutated nef or vpr genes had normal serum levels of NO metabolites and
      their macrophages produced normal levels of NO when stimulated. An explanation
      for the reduced NO response of HIV[Vpr+Nef+] macrophages was not apparent from
      measured levels of iNOS expression, viral gene expression, or arginase activity
      in activated macrophages. Inhibition of nitric oxide synthase (NOS) isoforms with
      L-NAME or aminoguanidine blocked time-dependent increases in HIV gene expression
      in activated macrophages cultured ex vivo. Inhibition with L-NAME occurred
      despite high levels of NO generated by iNOS, and exogenously supplied NO induced
      HIV gene expression only weakly, suggesting that cNOS had the greater influence
      on proviral gene induction. This system is presented as a model of HIV-1 proviral
      gene expression and dysfunction in macrophages.

PMID- 11590197
TI  - Differential regulation of transendothelial migration of THP-1 cells by ICAM
      1/LFA-1 and VCAM-1/VLA-4.
AB  - The adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular
      cell adhesion molecule 1 (VCAM-1) expressed in atherogenic lesions are thought to
      regulate monocyte diapedesis. To better understand their specific roles we used
      function-blocking antibodies and examined in a culture model the morphology,
      motility, and diapedesis of THP-1 cells interacting with human coronary artery
      endothelial cells. The number of motile THP-1 cells was reduced only when VCAM-1
      or both ICAM-1 and VCAM-1 were blocked. Blockade of ICAM-1 and VCAM-1, either
      separately or together, reduced to the same degree the distance that THP-1 cells
      traveled. Diapedesis was reduced only during the simultaneous blockade of both
      adhesion molecules. Blockade of either ICAM-1 or VCAM-1 inhibited pseudopodia
      formation, but ICAM-1 blockade induced the formation of filopodia. We suggest
      that the interactions of endothelial ICAM-1 and VCAM-1 with their ligands
      differentially regulate distinct steps of diapedesis by modulating the ratio of
      active and inactive forms of small GTPases such as Rho, Rac, and Cdc42.

PMID- 11590198
TI  - CCL18/DC-CK-1/PARC up-regulation in hypersensitivity pneumonitis.
AB  - Hypersensitivity pneumonitis (HP) is a lung inflammatory disorder characterized
      by accumulation of T lymphocytes. However, the mechanisms implicated in this
      process remain undefined. We examined the expression of dendritic cell (DC)
      derived CC chemokine 1 (CK1)/CCL18, a chemokine putatively involved in naive T
      cell recruitment, in lungs from 10 patients with HP, 9 patients with idiopathic
      pulmonary fibrosis (IPF), and 20 healthy lungs. CCL18 was measured by real-time
      quantitative PCR and localized in lungs by in situ hybridization and
      immunohistochemistry. CCL18 expression was significantly increased in lungs
      affected by HP in comparison with lungs affected by IPF (2,085+/-393 vs. 1,023+/
      110; P<0.05) and controls (2,085+/-393 vs. 467+/-94; P<0.01). Macrophages, DCs,
      and alveolar epithelial cells were the main sources of CCL18. There was a direct
      correlation between the levels of tissue CCL18 and the number of lymphocytes in
      the bronchoalveolar lavage fluids. High levels of CCL18 were detected in the
      subacute rather than the chronic phase of HP. These findings suggest a role for
      CCL18 in the pathogenesis of HP.

PMID- 11590199
TI  - A cytokine-to-chemokine axis between T lymphocytes and keratinocytes can favor
      Th1 cell accumulation in chronic inflammatory skin diseases.
AB  - The recruitment of T cells into the skin is regulated by chemokines released by
      resident cells. In this study, we found that normal human keratinocytes activated
      with Th1-derived supernatant (sup) expressed early (6-12 h) IP-10/CXCL10, MCP
      1/CCL2, IL-8/CXCL8, and I-309/CCL1 mRNAs and with slower kinetics (24-96 h),
      RANTES/CCL5 and MDC/CCL22 mRNAs. Upon stimulation with the Th1 sup, keratinocytes
      secreted high levels of RANTES, IP-10, MCP-1, and IL-8 and moderate levels of I
      309 and MDC. Although much less efficiently, Th2 sup could also induce
      keratinocyte expression of IL-8, IP-10, RANTES, and MCP-1 but not of I-309 and
      MDC. TARC/CCL17 was not significantly induced by any stimuli. Sup from
      keratinocytes activated with Th1-derived cytokines elicited a strong migratory
      response of Th1 cells and a limited migration of Th2 cells, whereas sup from Th2
      activated keratinocytes promoted a moderate migration of Th1 and Th2 lymphocytes.
      Thus, keratinocytes appear considerably more sensitive to Th1- than to Th2
      derived lymphokines in terms of chemokine release and can support the
      preferential accumulation of Th1 lymphocytes in the skin.

PMID- 11590200
TI  - IL-10 receptor dysfunction in macrophages during chronic inflammation.
AB  - The immunosuppressive activity of interleukin-10 (IL-10) makes this cytokine a
      potentially important clinical tool to reduce inflammatory responses in various
      diseases. Its efficacy as a therapeutic modality is dependent on the
      responsiveness of immune cells. We report that macrophages from mice chronically
      infected with the LP-BM5 retrovirus had a reduced capacity to respond to IL-10 in
      vitro. The ability of IL-10 to inhibit lipopolysaccharide-induced production of
      tumor necrosis factor (TNF) alpha and IL-6 was significantly reduced in both
      alveolar and peritoneal macrophages from infected versus uninfected mice. IL-10
      hyporesponsiveness was not related to direct infection by the retrovirus, because
      bone marrow-derived macrophages infected in vitro with LP-BM5 were as responsive
      to IL-10 as were uninfected bone marrow-derived macrophages. TNF-alpha appeared
      to contribute to development of IL-10 hyporesponsiveness, because exposure of
      normal macrophages to TNF-alpha but not interferon-gamma reduced macrophage
      responsiveness to IL-10. Reverse transcriptase-PCR and flow cytometry
      demonstrated normal expression of the alpha and beta chains of the IL-10 receptor
      in macrophages from infected mice, suggesting that IL-10 hyporesponsiveness is
      not related to a change in receptor expression. The potential role of reduced IL
      10 responsiveness in the chronicity of inflammation in this and other diseases is
      discussed.

PMID- 11590201
TI  - Selective attraction of naive and memory B cells by dendritic cells.
AB  - In this study, we investigate whether dendritic cells (DC), known to interact
      directly with T and B cells, might also contribute to the recruitment of B cells
      through the production of chemotactic factors. We found that B cells responded to
      several chemokines (CXCL12, CCL19, CCL20, and CCL21), which can be produced by DC
      upon activation. In addition, supernatant from DC (SNDC) potently and selectively
      attracted naive and memory B cells but not germinal center (GC) B cells or other
      lymphocytes (CD4(+), CD8(+) T cells or NK cells). Production of this activity was
      restricted to DC and was not increased following DC activation by LPS or CD40
      ligand. Surprisingly, the B-cell chemotactic response to SNDC was insensitive to
      pertussis toxin treatment. In addition, the chemotactic factor(s) appeared
      resistant to protease digestion and highly sensitive to heat. This suggested that
      the DC chemotactic factor(s) is different from classical chemoattractants and
      does not involve G(alpha(i)) proteins on the responding B lymphocytes. It is
      interesting that SNDC was able to synergize with several chemokines to induce
      massive migration of B lymphocytes. These observations show that DC spontaneously
      produce factors that, alone or in cooperation with chemokines, specifically
      regulate B-cell migration, suggesting a key role of DC in the recruitment or
      localization of B lymphocytes within secondary lymphoid organs.

PMID- 11590202
TI  - Involvement of p38-mitogen-activated protein kinase in Staphylococcus aureus
      induced neutrophil apoptosis.
AB  - Apoptosis occurred in human neutrophils within an hour of exposure to viable
      serum-opsonized Staphylococcus aureus, as indicated by appearance of cells with
      condensed nuclei, fragmented DNA, and increased phosphatidylserine exposure. In
      contrast, serum-opsonized, heat-killed S. aureus did not induce apoptosis. This
      discrepancy could not be explained by differences in bacterial uptake or total
      NADPH-oxidase activity. Suppressing phagocytosis by pretreating the neutrophils
      with cytochalasin b or by using nonopsonized bacteria did not prevent apoptosis.
      A supernatant from bacteria grown for 2 h in nutrient broth had a strong
      proapoptotic influence that was abrogated by heat treatment. Exposure to viable
      S. aureus or supernatant also led to activation of p38-mitogen-activated protein
      kinase in the neutrophils. Inhibition of this kinase with SB203580 reduced the
      apoptosis-inducing capacity of both bacteria and supernatant. We conclude that S.
      aureus activates p38-mitogen-activated protein kinase in neutrophils and induces
      apoptosis, probably mediated by a bacteria-derived soluble factor(s).

PMID- 11590203
TI  - Phosphatidylinositol 3-kinase and ERK are required for NF-kappaB activation but
      not for phagocytosis.
AB  - The molecular events that transduce signals from Fc receptors to the various
      cellular responses are still poorly defined. We have investigated the role of
      phosphatidylinositol 3-kinase (PI 3-K) and extracellular signal-regulated kinase
      (ERK) in gene activation and phagocytosis in monocytes. In the THP-1 monocytic
      cell line, cross-linking of Fc receptors by immune complexes results in
      activation of the transcription factor NF-kappaB, via activation of ERK.
      Activation of both ERK and NF-kappaB was blocked by wortmannin and LY294002,
      specific inhibitors of PI 3-K. Wortmannin also inhibited the Fc receptor-mediated
      increase in the cytosolic calcium concentration, but it did not block
      immunoglobulin G (IgG)-mediated phagocytosis. In addition, the ERK inhibitor
      PD98059 did not block phagocytosis of IgG-coated erythrocytes. Both the increase
      in the cytosolic calcium concentration and phagocytosis depend on an active actin
      cytoskeleton, as indicated by the total lack of both responses after treatment
      with cytochalasin B. In contrast, cytochalasin B did not affect Fc receptor
      mediated activation of NF-kappaB. These results identify PI 3-K and ERK as
      important signaling molecules in the Fc receptor signal transduction pathway of
      monocytes, which leads to the nucleus for gene activation. These results also
      suggest that, in contrast to other cell types, unstimulated monocytes do not
      require PI 3-K and ERK for phagocytosis.

PMID- 11590204
TI  - Crystal-induced neutrophil activation. VII. Involvement of Syk in the responses
      to monosodium urate crystals.
AB  - The inflammatory response in acute gouty arthritis is in large part a result of
      the interaction between neutrophils and monosodium urate (MSU) crystals. The
      tyrosine kinase Syk, which has been largely associated with the phagocytic
      response by Fc receptors and with spreading mediated by integrins, has been
      identified as one of the major proteins tyrosine-phosphorylated in human
      neutrophils upon stimulation by MSU crystals and is known to be mediated in part
      by the Fc receptor, CD16. This has led to the present examination of the
      implication of Syk in the activation pathways used by MSU crystals. The tyrosine
      phosphorylation patterns induced by MSU crystals and by the ligation of CD16 were
      inhibited by piceatannol, which, conversely, only slightly delayed but did not
      diminish the peak of tyrosine phosphorylation induced by cross-linking CD32 or by
      the addition of fMet-Leu-Phe. Moreover, piceatannol inhibited the activity of Syk
      as monitored by in vitro kinase assays, by its in situ tyrosine phosphorylation,
      and by its activity toward exogenous substrates after stimulation by MSU
      crystals. We also measured the impact of piceatannol on the mobilization of
      calcium, the production of superoxide anions, and the activity of PLD stimulated
      by MSU crystals. We noted a distinct inhibition of all these responses by
      piceatannol. Finally, the morphological changes observed in neutrophils as
      characteristic of MSU crystal internalization were diminished significantly by
      piceatannol. The results obtained show that Syk plays a critical and central role
      in the signal-transduction pathways called upon by MSU crystals subsequent to
      their interaction with human neutrophils.

PMID- 11590205
TI  - Association of ARF and Rabs with complement receptor type-1 storage vesicles in
      human neutrophils.
AB  - During neutrophil activation, the properties of the cell are rapidly altered by
      increases in the surface expression of functionally important receptors and
      adherence molecules. At the same time, endocytic and phagocytic activities
      increase. These alterations require precise regulation of membrane and protein
      movement, which is achieved, at least in part, by bidirectional movement of small
      transport vesicles. GTP-binding proteins, including Rabs and ADP-ribosylation
      factors (ARFs), play critical roles in regulating vesicle trafficking in other
      types of cells. The ability to immunoisolate the "secretory" vesicle
      subpopulation in which complement receptor type 1 (CR1) is stored allowed us to
      determine which types of low-molecular-weight GTP-binding proteins interact with
      these vesicles and under what conditions. CR1-containing vesicles from resting
      human neutrophils constitutively copurify with Rabs 3a, 4, and 5a, and reversibly
      bind an ARF, likely ARF1. ARF binding is dependent on free Mg(2+) and is enhanced
      by GTPgammaS. Mg(2+) at 0.4 microM is necessary for half-maximal binding of ARFs
      to CR1 storage vesicles. Artificial phospholipid vesicles and primary and
      secondary granules from human neutrophils do not bind ARFs themselves and do not
      compete for recruitment of ARFs to CR1 vesicles, suggesting that specific
      membrane environments and/or proteins on these vesicles stabilize the ARF-GTP
      Mg(2+) complex. Free Ca(2+) at 300 nM does not inhibit ARF binding to CR1 storage
      vesicles, but 10 mM Ca(2+) does reduce such binding. These findings suggest that
      ARF-GTP specifically and reversibly interacts with CR1 storage vesicles in human
      polymorphonuclear leukocytes and may play a role in regulating their transport.

PMID- 11590206
TI  - Apolipoprotein E and mimetic peptide initiate a calcium-dependent signaling
      response in macrophages.
AB  - Apolipoprotein E (ApoE) is a 34-kDa cholesterol transport protein that also
      possesses immunomodulatory properties. In this study, we demonstrate that ApoE
      initiates a signaling cascade in murine peritoneal macrophages that leads to
      increased production of inositol triphosphate with mobilization of intracellular
      Ca(2+) stores. This cascade is inhibited by pretreatment with receptor-associated
      protein and Ni(2+), and it is mediated by a pertussis toxin-sensitive G protein.
      These properties are characteristic of signal transduction induced via ligand
      binding to the cellular receptor, lipoprotein receptor-related protein. A peptide
      derived from the receptor-binding region of ApoE also initiates signal
      transduction in a manner similar to that of the intact protein, suggesting that
      this isolated region is sufficient for signal transduction. The ApoE-mimetic
      peptide competed for binding with the intact protein, confirming that they both
      interact with the same site. ApoE-dependent signal transduction might play a role
      in mediating the functional properties of this lipoprotein.

PMID- 11590207
TI  - Role of ABCG1 and other ABCG family members in lipid metabolism.
AB  - The molecular cloning and identification of mutations in ATP-binding cassette
      transporters in hereditary diseases have greatly expanded our knowledge of the
      normal physiology of intracellular lipid transport processes. In addition to the
      well-known ATP-binding cassette transporter A1 (ABCA1) molecule, ABC transporters
      belonging to the ABCG (White) subfamily (ABCG1, ABCG5, and ABCG8) have been shown
      to be critically involved in the regulation of lipid-trafficking mechanisms in
      macrophages, hepatocytes, and intestinal mucosa cells. ABCG1, the product of a
      sterol-induced gene, participates in cholesterol and phospholipid efflux. The
      ABCG5 and ABCG8 transporters, defective in beta-sitosterolemia, are also now
      considered interesting targets in the control and influence of total body sterol
      homeostasis. In this review, advances referring to the regulation and function of
      ABCG half-size transporters are summarized and discussed. In addition, new
      implications for the transcriptional control, as well as the intracellular
      routing and localization, of these proteins are presented.

PMID- 11590208
TI  - Sources of eicosanoid precursor fatty acid pools in tissues.
AB  - Tissue arachidonic acid (AA) pools originate from the diet, and from hepatic and
      extrahepatic desaturation-elongation of dietary linoleic acid (LA). This review
      summarizes the roles of absorption, transport, and formation of AA in the buildup
      of tissue AA pools. In humans who ingest 0.2-0.3 g of AA and 10-20 g of LA per
      day on a Western diet, the formation of AA from LA exceeds the dietary supply of
      AA. A number of factors favor the partitioning of AA to tissue phospholipids
      rather than adipose tissue and plasma triglycerides. The characteristics of AA
      transport with lipoproteins are discussed with focus on the role of lipoprotein
      lipase, lecithin:cholesterol acyltransferase, hepatic lipase, and the scavenger
      receptor BI and LDL receptors in tissue uptake of AA. Liver-derived 2-acyl
      lysophosphatidylcholine and plasma free AA are two important sources of AA for
      extrahepatic tissues which exhibit a low rate of uptake of lipoprotein AA.
      Desaturation-elongation of LA to produce AA occurs both in liver and in
      extrahepatic tissues, plasma free LA being an important substrate particularly
      during fasting. The AA preference of the reacylation and transacylation reactions
      is crucial for the selective retention of AA in phospholipids.

PMID- 11590209
TI  - Effects of fenofibrate on lipid parameters in obese rhesus monkeys.
AB  - Fenofibrate is a member of the fibrate class of hypolipidemic agents used
      clinically to treat hypertriglyceridemia and mixed hyperlipidemia. The fibrates
      were developed primarily on the basis of their cholesterol and triglyceride
      lowering in rodents. Fibrates have historically been ineffective at lowering
      triglycerides in experimentally-induced dyslipidemia in nonhuman primate models.
      The spontaneously obese rhesus monkey is a well-recognized animal model for the
      study of human obesity and type 2 diabetes, and many of these monkeys exhibit
      naturally occurring lipid abnormalities, including elevated triglycerides and low
      HDL cholesterol (HDL-C), similar to patients with type 2 diabetes. To explore
      whether the obese rhesus model was predictive of the lipid lowering effects of
      fibrates, we evaluated fenofibrate in six hypertriglyceridemic, hyperinsulinemic,
      nondiabetic animals in a 20-week, dose-escalating study. The study consisted of a
      4-week baseline period, two treatment periods of 10 mg/kg twice daily (b.i.d) for
      4 weeks and 30 mg/kg b.i.d. for 8 weeks, and a 4-week washout period. Fenofibrate
      (30 mg/kg b.i.d) decreased serum triglycerides 55% and LDL-C 27%, whereas HDL-C
      increased 35%. Apolipoproteins B-100 and C-III levels were also reduced 70% and
      29%, respectively. Food intake, body weight, and plasma glucose were not affected
      throughout the study. Interestingly, plasma insulin levels decreased 40% during
      the 30 mg/kg treatment period, suggesting improvement in insulin sensitivity.
      These results support the use of obese rhesus monkey as an excellent animal model
      for studying the effects of novel hypolipidemic agents, particularly agents that
      impact serum triglycerides and HDL-C.

PMID- 11590210
TI  - Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with
      mutations of apolipoprotein B gene.
AB  - We report the clinical phenotype in three kindreds with familial heterozygous
      hypobetalipoproteinemia (FHBL) carrying novel truncated apolipoprotein Bs (apoBs)
      of different sizes (apoB-8.15, apoB-33.4 and apoB-75.7). In D.A. kindred, we
      found three carriers of a C-deletion in exon 10 leading to the synthesis of apoB
      8.15 not detectable in plasma. They showed steatorrhea and fatty liver. In N.L.
      kindred, the proband is heterozygous for a nonsense mutation in exon 26, leading
      to the formation of apoB-33.4. He had premature cerebrovascular disease and fatty
      liver; two apoB-33.4 carriers in this kindred showed only fatty liver. In B.E.
      kindred, the proband is heterozygous for a T-deletion in exon 26, which converts
      tyrosine at codon 3435 into a stop codon, resulting in apoB-75.7. The proband, a
      heavy alcohol drinker, had steatohepatitis, whereas his teetotaller daughter, an
      apoB-75.7 carrier, had no detectable fatty liver. This study suggests that: i)
      fatty liver invariably develops in FHBL carriers of short and medium-size
      truncated apoBs (< apoB-48), but its occurrence needs additional environmental
      factors in carriers of longer apoB forms; ii) intestinal lipid malabsorption
      develops only in carriers of short truncated apoBs, which are not secreted into
      the plasma; and iii) cerebrovascular disease due to premature atherosclerosis may
      occur even in FHBL subjects.

PMID- 11590211
TI  - Sphingosylphosphorylcholine is an activator of transglutaminase activity in human
      keratinocytes.
AB  - We characterize functional roles of a newly discovered chemical,
      sphingosylphosphorylcholine (SPC), in the epidermis by elucidating the biological
      effect of SPC on human keratinocytes in culture. The intracellular calcium level
      of human keratinocytes was increased by incubation with SPC, but not with
      sphingosine (SS) or sphingomyelin (SM). The addition of SPC, sphingosine 1
      phosphate (SSP), or SS to human keratinocytes at 10 microM concentrations also
      significantly suppressed DNA synthesis, and SPC, but not SSP, or SS increased the
      activities of membrane-bound and soluble transglutaminases (TGases). Reverse
      transcription polymerase chain reaction (RT-PCR) of TGase transcripts revealed
      that SPC treatment at 10 microM concentrations increased the expression of TGase
      1 mRNA. The increased activity of soluble TGase was accompanied by the
      concomitant activation of cathepsin D as revealed by the increased ratio of
      mature active form to inactive intermediate form of the protease. Pretreatment of
      human keratinocytes with pepstatin, a protease inhibitor, blocked the increase in
      soluble TGase activity induced by treatment with SPC. Consistently, SPC treatment
      at 1-10 microM concentrations stimulated the cornified envelope formation. These
      findings suggest that SPC plays an important role in the altered keratinization
      process of epidermis in skin diseases with high expression of sphingomyelin
      deacylase, such as atopic dermatitis.

PMID- 11590212
TI  - Identification of unusual 7-oxygenated bile acid sulfates in a patient with
      Niemann-Pick disease, type C.
AB  - Niemann-Pick disease, type C, was diagnosed in a 3-month-old boy with
      hepatosplenomegaly, mild signs of cholestasis, hepatic inflammation and
      extramedullary erythropoiesis, together with chronic airway disease. He developed
      muscular hypotonia, psychomotor retardation, rickets, and signs of peripheral
      neuropathy. The patient was found to excrete abnormal amounts of unusual bile
      acids in urine at 3 and 5 months of age. These acids were shown to have a 3beta
      hydroxy-Delta(5) structure and to carry an oxo or hydroxy group at C-7. They were
      sulfated at C-3 and nonamidated or conjugated with glycine or taurine at C-24.
      Part of the 7-hydroxy acids, presumably the 7beta-hydroxylated one, was also
      conjugated with N-acetylhexosamine, probably N-acetylglucosamine, at the 7
      hydroxy group. Possible metabolic pathways for the formation of the 7-oxo and
      7beta-hydroxycholenoic acids are discussed. Based on previous data concerning the
      effects of 3beta-hydroxy-Delta(5) bile acids on bile acid transport, it is
      suggested that the formation of such bile acids is responsible for the
      cholestasis in this patient.

PMID- 11590213
TI  - Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by
      lipoprotein lipase in wild-type and apoE knockout mice.
AB  - Previous studies with hypertriglyceridemic APOC3 transgenic mice have suggested
      that apolipoprotein C-III (apoC-III) may inhibit either the apoE-mediated hepatic
      uptake of TG-rich lipoproteins and/or the lipoprotein lipase (LPL)-mediated
      hydrolysis of TG. Accordingly, apoC3 knockout (apoC3(-/-)) mice are
      hypotriglyceridemic. In the present study, we attempted to elucidate the
      mechanism(s) underlying these phenomena by intercrossing apoC3(-/-) mice with
      apoE(-/-) mice to study the effects of apoC-III deficiency against a
      hyperlipidemic background. Similar to apoE(+/+) apoC3(-/-) mice, apoE(-/-)apoC3(
      /-) mice exhibited a marked reduction in VLDL cholesterol and TG, indicating that
      the mechanism(s) by which apoC-III deficiency exerts its lipid-lowering effect
      act independent of apoE. On both backgrounds, apoC3(-/-) mice showed normal
      intestinal lipid absorption and hepatic VLDL TG secretion. However, turnover
      studies showed that TG-labeled emulsion particles were cleared much more rapidly
      in apoC3(-/-) mice, whereas the clearance of VLDL apoB, as a marker for whole
      particle uptake by the liver, was not affected. Furthermore, it was shown that
      cholesteryl oleate-labeled particles were also cleared faster in apoC3(-/-) mice.
      Thus the mechanisms underlying the hypolipidemia in apoC3(-/-) mice involve both
      a more efficient hydrolysis of VLDL TG as well as an enhanced selective clearance
      of VLDL cholesteryl esters from plasma. In summary, our studies of apoC3(-/-)
      mice support the concept that apoC-III is an effective inhibitor of VLDL TG
      hydrolysis and reveal a potential regulating role for apoC-III with respect to
      the selective uptake of cholesteryl esters.

PMID- 11590214
TI  - Intravenous apoA-I/lecithin discs increase pre-beta-HDL concentration in tissue
      fluid and stimulate reverse cholesterol transport in humans.
AB  - The extent to which plasma HDL concentration regulates reverse cholesterol
      transport (RCT) is not known. The principal acceptors of unesterified cholesterol
      (UC) from cultured cells are small pre-beta-HDL, which we have shown increase in
      plasma during intravenous infusion of apolipoprotein A-I/phosphatidylcholine
      (apoA-I/PC) discs in humans. We have now examined the effects on tissue fluid HDL
      and RCT. ApoA-I/PC or proapoA-I/PC discs were infused into 16 healthy males.
      Eleven had been given intravenous radiocholesterol to label tissue pools; in 12
      prenodal leg lymph was collected throughout; and in 8 all feces were collected.
      The rise in small pre-beta-HDL in plasma was associated with increases in 1) pre
      beta-HDL concentration in lymph (all subjects), 2) the size of other lymph HDL
      (four of four subjects), 3) the cholesterol content of lymph lipoproteins
      relative to plasma lipoproteins (P < 0.01, n = 4), 4) cholesterol-specific
      radioactivity in lymph (five of nine subjects), 5) plasma lathosterol (P < 0.004,
      n = 4), 6) plasma cholesterol esterification rate (P < 0.001, n = 4), and 7)
      fecal bile acid excretion (P < 0.001, n = 8). These results support the
      hypothesis that small pre-beta-HDL generated in plasma readily cross endothelium
      into tissue fluid, and thereby promote efflux of UC from peripheral cells. After
      delivery to the liver, peripheral cholesterol appears to be utilized more for
      bile acid synthesis than for biliary cholesterol secretion in humans.

PMID- 11590215
TI  - Alternate pathways of bile acid synthesis in the cholesterol 7alpha-hydroxylase
      knockout mouse are not upregulated by either cholesterol or cholestyramine
      feeding.
AB  - Bile acids are synthesized via the classic pathway initiated by cholesterol
      7alpha-hydroxylase (CYP7A1), and via alternate pathways, one of which is
      initiated by sterol 27-hydroxylase (CYP27). These studies used mice lacking
      cholesterol 7alpha-hydroxylase (Cyp7a1(-/-)) to establish whether the loss of the
      classic pathway affected cholesterol homeostasis differently in males and
      females, and to determine if the rate of bile acid synthesis via alternate
      pathways was responsive to changes in the enterohepatic flux of cholesterol and
      bile acids. In both the Cyp7a1(-/-) males and females, the basal rate of bile
      acid synthesis was only half of that in matching Cyp7a1(+/+) animals. Although
      bile acid pool size contracted markedly in all the Cyp7a1(-/-) mice, the female
      Cyp7a1(-/-) mice maintained a larger, more cholic acid-rich pool than their male
      counterparts. Intestinal cholesterol absorption in the Cyp7a1(-/-) males fell
      from 46% to 3%, and in the matching females from 58% to 17%. Bile acid synthesis
      in Cyp7a1(+/+) males and females was increased 2-fold by cholesterol feeding, and
      4-fold by cholestyramine treatment, but was not changed in matching Cyp7a1(-/-)
      mice by either of these manipulations. In the Cyp7a1(-/-) mice fed cholesterol,
      hepatic cholesterol concentrations increased only marginally in the males, but
      rose almost 3-fold in the females. CYP7A1 activity and mRNA levels were greater
      in females than in males, and were increased by cholesterol feeding in both
      sexes. CYP27 activity and mRNA levels did not vary as a function of CYP7A1
      genotype, gender, or dietary cholesterol intake. We conclude that in the mouse
      the rate of bile acid synthesis via alternative pathways is unresponsive to
      changes in the enterohepatic flux of cholesterol and bile acid, and that factors
      governing gender-related differences in bile acid synthesis, pool size, and pool
      composition play an important role in determining the impact of CYP7A1 deficiency
      on cholesterol homeostasis in this species.

PMID- 11590216
TI  - Determination of lipid-bound sulfate by ion chromatography and its application to
      quantification of sulfolipids from kidneys of various mammalian species.
AB  - A variety of procedures have been developed for determining the sulfate ester
      content of various biomolecules. Ion chromatography (IC), that is, quantitation
      of ionic substances by ion conductimetry after separation by anion-exchange
      chromatography, has been increasingly utilized for the determination of inorganic
      sulfate in clinical and environmental samples. We adopted suppressed-mode IC to
      the determination of lipid- or glycolipid-bound sulfate released by acid
      hydrolysis and found that it has the advantage of increased precision for wide
      concentration ranges (30 pmol to approximately micromol) and lack of interference
      from other lipids. To minimize deterioration of the separation column, the
      lipophilic constituents in the acid hydrolysate were removed by a two-phase
      partition system of chloroform-methanol-water. The inorganic sulfate was
      quantitatively extracted into the aqueous phase by replacing water with an
      alkaline buffer. By this method, the concentration of sulfolipids was determined
      in the kidney of mammals with various body mass. Sulfolipids were more
      concentrated in the kidney of smaller animals, which have higher maximum urine
      concentrating activity per gram of body mass, supporting the hypothesis of the
      function of sulfolipids as an ion barrier on the luminal surface of renal
      tubules.

PMID- 11590217
TI  - Microsomal membrane-associated apoB is the direct precursor of secreted VLDL in
      primary cultures of rat hepatocytes.
AB  - Brefeldin A (BFA) added to primary cultures of rat hepatocytes, at a
      concentration of 0.2 microg/ml, prevented the assembly of newly synthesized
      apolipoprotein B (apoB) into mature, secretory VLDL but did not prevent the
      secretion of apoB as denser particles (HDL apoB), or of albumin. The unassembled
      apoB remained associated with the membranes of the cellular microsomal fraction.
      There was no effect of BFA on the removal of apoB from the lumen of these
      vesicles. VLDL apoB formed only a minor component of the total apoB in the
      microsomal lumen. Higher (5 microg/ml) concentrations of BFA were required to
      prevent the secretion of HDL apoB and albumin. Under these conditions apoB
      accumulated in the microsomal lumen, as well as in the membranes of these
      vesicles. Again, apoB VLDL formed only a minor proportion of the total lumenal
      apoB. ApoB-48 VLDL and apoB-100 VLDL assembly could be restored by removing BFA
      from the medium. This reactivation of VLDL assembly was accompanied by an
      increased removal of apoB from the microsomal membranes, but there was no
      detectable increase in the small quantity of VLDL apoB that was recovered from
      the microsomal lumen. In the absence of BFA, during pulse-chase experiments the
      pattern of change in the specific radioactivity of microsomal membrane apoB was
      similar to that of the secreted VLDL apoB whereas that of the lumenal apoB
      resembled that of the secreted HDL apoB. The results suggest that membrane
      associated apoB is the main direct precursor of secreted VLDL apoB in primary
      cultures of rat hepatocytes and that VLDL assembly does not involve primarily
      microsomal lumenal apoB as an intermediate.

PMID- 11590218
TI  - Effects of palm oil and transesterified palm oil on chylomicron and VLDL
      triacylglycerol structures and postprandial lipid response.
AB  - The effects of positional distribution of triacylglycerol (TAG) fatty acids to
      TAG structures in chylomicrons and VLDL, and to postprandial lipemia, were
      studied in 10 healthy premenopausal women using a 6-h oral fat load test and a
      randomized, double-blind cross-over design. Molecular level information of TAG
      regioisomerism was obtained with a tandem mass spectrometric method. The
      positional distribution of fatty acids in chylomicron TAGs was similar to the
      respective dietary fat; 79% of the analyzed regioisomers in palm oil and 84% of
      the analyzed regioisomers in transesterified oil were found in chylomicron TAGs 3
      h after the oral fat loads. VLDL TAGs were equal after the two fat loads in all
      but one regioisomer. Similarities in the fatty acid compositions of chylomicron
      TAGs suggest that palmitic acid was absorbed equally from both test fats. The
      proportion of palmitoleic acid in the chylomicrons was increased. Fat with
      palmitic acid predominantly in the sn-1 and sn-3 positions caused a larger
      incremental area of total TAGs in plasma and reduced plasma insulin values at the
      beginning of the postprandial response (0-90 min) compared with fat with palmitic
      acid randomly distributed. The relationship between TAG molecular structures in
      dietary fats and in lipoproteins provides new means for understanding the effects
      of fatty acid positional distribution on human lipid metabolism.

PMID- 11590219
TI  - Alteration of plasma HDL cholesteryl ester composition with transgenic expression
      of a point mutation (E149A) of human LCAT.
AB  - We have previously identified a single amino acid mutation (hE149A) in human LCAT
      that increases its in vitro reactivity with phosphatidylcholine species
      containing sn-2 arachidonate (Wang et al. 1997. J. Biol. Chem. 272: 280-286). The
      purpose of the present study was to determine whether in vivo overexpression of
      hE149A compared with human wild-type LCAT (hLCAT-wt) would be sufficient to
      enrich the steady state composition of plasma HDL cholesteryl esters (CE) with
      long chain (>18 carbon) polyunsaturated fatty acyl species. Transgenic lines with
      20-fold overexpression of hLCAT were created and studied between 12 and 16 weeks
      of age while consuming a chow diet. Transgenic overexpression of hE149A compared
      with hLCAT-wt significantly enriched HDL with CE species containing 20:4 (45%)
      and 22:6 n-3 (108%), at the expense of those containing 18:2, without a
      significant change in the plasma HDL concentration, particle size, or
      phospholipid fatty acyl composition. Removing the contribution of endogenous
      mouse LCAT by crossing the transgenic mice into the mouse LCAT knockout
      background resulted in even greater changes in HDL CE composition, with a 2.4-, 5
      , and 5-fold increase in 20:4, 20:5 n-3, and 22:6 n-3 cholesteryl esters in the
      hE149A mice compared with hLCAT-wt Tg mice, respectively. Our results demonstrate
      that in vivo expression of hE149A significantly enriches HDL cholesteryl esters
      in 20- and 22-carbon fatty acyl species without affecting HDL concentration or
      size. Furthermore, the data suggest that endogenous mouse LCAT in hLCAT
      transgenic mice contributes to the plasma HDL CE pool out of proportion to its
      mass, presumably because the hLCAT transgene is poorly activated by mouse
      apolipoprotein A-I.

PMID- 11590220
TI  - Regulation of scavenger receptor class B type I in hamster liver and Hep3B cells
      by endotoxin and cytokines.
AB  - Multiple changes in HDL metabolism occur during infection and inflammation that
      could potentially impair the antiatherogenic functions of HDL. Scavenger receptor
      class B type I (SR-BI) promotes cholesterol efflux from peripheral cells and
      mediates selective uptake of cholesteryl ester into hepatocytes, thereby playing
      a pivotal role in reverse cholesterol transport. We studied the effect of
      endotoxin (lipopolysaccharide, LPS) and cytokines [tumor necrosis factor (TNF)
      and interleukin 1 (IL-1)] on hepatic SR-BI mRNA and protein levels in Syrian
      hamsters. LPS significantly decreased SR-BI mRNA levels in hamster liver. This
      effect was rapid and sustained, and was associated with a decrease in hepatic SR
      BI protein levels. High cholesterol diet did not change hepatic SR-BI mRNA
      levels, and LPS was able to decrease SR-BI mRNA levels during high cholesterol
      feeding. TNF and IL-1 decreased SR-BI mRNA levels in the liver, and the effects
      of TNF and IL-1 were additive. TNF and IL-1 also decreased SR-BI levels in Hep3B
      hepatoma cells. More importantly, TNF and IL-1 decreased the uptake of HDL
      cholesteryl ester into Hep3B cells. In addition, we studied the effect of LPS on
      SR-BI mRNA in RAW 264.7 cells, a macrophage cell line. LPS rapidly decreased SR
      BI mRNA levels in RAW 264.7 cells, but the effect was not sustained and did not
      lead to a reduction in SR-BI protein levels. Our results suggest that the
      decrease in hepatic SR-BI levels due to LPS and cytokines during infection and
      inflammation may decrease selective uptake of cholesteryl ester into the liver
      and result in impaired reverse cholesterol transport.

PMID- 11590221
TI  - N-linked glycosylation of macrophage-derived PAF-AH is a major determinant of
      enzyme association with plasma HDL.
AB  - Human plasma PAF-AH (platelet-activating factor-acetylhydrolase) is a Ca(2)+
      independent phospholipase A2 of hematopoietic origin associated with LDL and HDL;
      it degrades PAF and oxidizes phospholipids. We show that human macrophages
      synthesize PAF-AH as a premedial Golgi precursor containing high mannose N-linked
      glycans. Secreted PAF-AH possesses a molecular mass of approximately 55 kDa and
      contains mature N-linked glycans. Secreted PAF-AH activity (90 +/- 4% of the
      total) bound to a wheat germ lectin column and could be eluted with N
      acetylglucosamine, whereas digestion with N-acetylneuraminidase II completely
      abolished enzyme absorption. Tunicamycin significantly reduced cell-associated
      PAF-AH activity and inhibited enzyme secretion; but it did not alter the ratio of
      secreted to cell-associated enzyme (1.8 at 6 h and 3.1 at 24 h), suggesting that
      glycosylation is not essential for PAF-AH secretion. Digestion of cell-associated
      PAF-AH or secreted PAF-AH with peptide N-glycosidase F affected neither catalytic
      activity nor its resistance to proteolysis with trypsin or proteinase K; in
      addition, it did not affect PAF-AH association with LDL, but significantly
      increased its association with HDL. We suggest that macrophage-derived PAF-AH
      contains heterogeneous asparagine-conjugated sugar chain(s) involving sialic
      acid, which hinders its association with HDL but does not influence the
      secretion, catalytic activity, or resistance of PAF-AH to proteases.

PMID- 11590222
TI  - Reversibility of n-3 fatty acid deficiency-induced alterations of learning
      behavior in the rat: level of n-6 fatty acids as another critical factor.
AB  - Rats fed a semipurified diet supplemented with 3% (w/w) safflower oil [Saf, n-3
      fatty acid deficient, high linoleic acid (18:2n-6)] through two generations
      exhibit decreased correct response ratios in a brightness-discrimination learning
      test compared with rats fed 3% perilla oil [Per, high alpha-linolenic acid (18:3n
      3)]. This is associated with a decreased DHA (22:6n-3)-to-arachidonic acid (20:4n
      6) ratio in brain lipids. In the first set of experiments, dietary oil was
      shifted from Saf to a mixture of 2.4% safflower oil plus 0.6% DHA after weaning
      (Saf-DHA), but all parameters measured in the learning test were essentially
      unchanged. Brain 22:6n-3 content of the Saf-DHA group reached that of the Per
      group but the levels of 20:4n-6 and docosatetraenoic acid (22:4n-6) did not
      decrease to those of the Per group at the start of the test. In the second set of
      experiments, dietary oil was shifted to a mixture of 0.6% safflower oil plus 1.2%
      oleic acid (OA) plus 1.2% DHA (Saf-OA-DHA group) with 18:2n-6 content comparable
      to that of the Per group. The Saf-OA-DHA group exhibited a learning performance
      similar to that of the Per group; brain 22:6n-3, 20:4n-6, and 22:4n-6 contents
      were also comparable to those of the Per group. These results indicate that the
      altered learning behavior associated with a long-term n-3 fatty acid deficiency
      is reversed by supplementing 22:6n-3 after weaning, when the levels of competing
      n-6 fatty acids in the diet and brain lipids are limited.

PMID- 11590223
TI  - Oxidative events cause degradation of apoB-100 but not of apo[a] and facilitate
      enzymatic cleavage of both proteins.
AB  - Lipoprotein [a] (Lp[a]) contains equimolar amounts of apoB-100 and apolipoprotein
      [a] (apo[a]). Both proteins are amenable to degradation in vivo by mechanisms yet
      to be clearly defined. In this study, we examined the in vitro susceptibility of
      LDL and Lp[a], obtained from the same donor, to oxidation by either Cu(2)+ or the
      combined Crotalus adamanteus phospholipase A2 and soybean lipoxygenase system,
      monitoring the course of the reaction by the generation of conjugated dienes and
      fatty acids. In some experiments, treatment with leukocyte elastase (LE) or
      matrix metalloproteinase 12 (MMP-12) was administered before and after the
      oxidative step. In the case of Lp[a] we found that with both oxidizing systems,
      conditions that caused the breakdown of apoB-100 did not degrade apo[a] although
      oxidation-mediated changes were detected in the latter by intrinsic tryptophan
      fluorescence spectroscopy. Similar results were obtained with a reassembled Lp[a]
      obtained by incubating free apo[a] with LDL. Both apo[a] and apoB-100 were
      cleaved by LE and MMP-12 but the enzymatic cleavage was more marked when the
      preoxidized proteins were used as a substrate. Taken together, our in vitro
      studies indicate that apo[a] but not apoB-100 resists oxidative fragmentation,
      whereas both proteins are cleaved by enzymes of the serine and metalloproteinase
      families. We speculate that the fragments of apo[a] observed in vivo may be
      preferentially generated by proteolytic rather than oxidative events, whereas
      apoB-100 can be degraded by both mechanisms.

PMID- 11590224
TI  - Anti-leptin receptor antibody mimics the stimulation of lipolysis induced by
      leptin in isolated mouse fat pads.
AB  - An anti-leptin receptor polyclonal antibody (receptor antibody), as well as
      leptin, stimulated the release of free fatty acids from isolated mouse fat pads
      in a time-dependent manner. Following a 90-min incubation, maximal lipolysis was
      observed at 6 microg/ml receptor antibody and 0.1 nM leptin. The receptor
      antibody did not show any additive effect to the stimulation of lipolysis induced
      by leptin, suggesting that they exert their actions through a similar mechanism
      involving the leptin receptor. N-[2-(p-bromocinnamylamino)ethyl]-5
      isoquinolinesulfonamide (H-89), quin 2-AM, N-(6-aminohexyl)-5-chloro-1
      naphthalenesulfonamide (W-7), and neomycin sulfate (neomycin) all potently
      inhibited the stimulation of lipolysis by the receptor antibody and leptin. Short
      term incubation of the fat pads with the receptor antibody or leptin showed a
      transient increase in the cellular content of cAMP and myo-inositol 1,4,5
      trisphosphate (IP3) in similar concentrations to the free fatty acid release.
      Quin 2-AM and W-7 also inhibited the increase in cAMP content, suggesting that a
      Ca(2)+/calmodulin-dependent process may be involved in a part of the mechanism in
      which the receptor antibody and leptin exert their effects. The increase in
      cellular IP3 content via phosphoinositide-specific phospholipase C (PLC)
      sensitive to neomycin appears to be a primary step to initiate intracellular
      events. Both the receptor antibody and leptin may stimulate the lipolysis through
      mechanisms involving a transient increase in the cellular IP3 content followed by
      cAMP production, which leads to the activation of cAMP-dependent protein kinase.

PMID- 11590225
TI  - Arachidonate metabolism and the signaling pathway of induction of apoptosis by
      oxidized LDL/oxysterol.
AB  - Owing at least in part to oxysterol components that can induce apoptosis,
      oxidized LDL (oxLDL) is cytotoxic to mammalian cells with receptors that can
      internalize it. Vascular cells possess such receptors, and it appears that the
      apoptotic response of vascular cells to the oxysterols borne by oxLDL is an
      important part of the atherogenic effects of oxLDL. Thus, an analysis of the
      signaling pathway of apoptotic induction by oxysterols is of value in
      understanding the development of atherosclerotic plaque. In a prior study, we
      demonstrated an induction of calcium ion flux into cells treated with 25
      hydroxycholesterol (25-OHC) and showed that this response is essential for 25-OHC
      induced apoptosis. One possible signal transduction pathway initiated by calcium
      ion fluxes is the activation of cytosolic phospholipase A2 (cPLA2). In the
      current study, we demonstrate that activation of cPLA2 does occur in both
      macrophages and fibroblasts treated with 25-OHC or oxLDL. Activation is evidenced
      by 25-OHC-induced relocalization of cPLA2 to the nuclear envelope and arachidonic
      acid release. Loss of cPLA2 activity, either through genetic knockout in mice, or
      by treatment with a cPLA2 inhibitor, results in an attenuation of arachidonic
      acid release as well as of the apoptotic response to oxLDL in peritoneal
      macrophages or to 25-OHC in cultured fibroblast and macrophage cell lines.

PMID- 11590226
TI  - Regulation of sterol regulatory element-binding proteins by cholesterol flux in
      CaCo-2 cells.
AB  - The regulation of sterol regulatory element-binding proteins (SREBP) by
      cholesterol flux was studied in the intestinal cell line CaCo-2. CaCo-2 cells
      were incubated for 18 h with micelles containing 5 mM taurocholate and 500 microM
      oleic acid or micelles containing either 200 microM cholesterol or 150 microM
      lysophosphatidylcholine. In some incubations, an ACAT inhibitor was added or 25
      hydroxycholesterol was substituted for cholesterol. The SREBP-1a transcript was 2
      fold more abundant than the SREBP-1c transcript. In cells incubated with micelles
      containing cholesterol, rates of cholesterol synthesis were decreased and rates
      of esterification were increased. Cholesterol synthesis was decreased further by
      ACAT inhibition. Cholesterol influx decreased mRNA levels of SREBP-2, HMG-CoA
      synthase, HMG-CoA reductase, and fatty acid synthase. ACAT inhibition modestly
      suppressed gene expression further. Neither SREBP-1a nor SREBP-1c mRNA levels
      were altered by cholesterol. Despite decreases in gene expression of the sterol
      responsive genes by cholesterol, the amounts of precursor and mature forms of
      SREBP-1 and SREBP-2 were not altered. In contrast, if 25-hydroxycholesterol was
      substituted for cholesterol, both the precursor and mature forms of SREBP-2 were
      decreased. The polar sterol decreased the mature form of SREBP-1 but the amount
      of the precursor form was unchanged. In cells incubated with micelles containing
      lysophosphatidylcholine, which causes cholesterol to efflux from cells, sterol
      responsive gene expression was increased. The amounts of precursor and mature
      forms of SREBP-1 and SREBP-2, however, were not altered. In contrast, if the
      cells were depleted of cholesterol by incubating them with lovastatin and
      cyclodextrin, the mature forms of SREBP-1 and SREBP-2 were increased, as were
      mRNA levels for the sterol-responsive genes. The data would suggest that
      cholesterol influx/efflux regulates mRNA levels of sterol-responsive genes
      independently of changes in the amount of mature SREBP. In contrast, 25
      hydroxycholesterol influx or cholesterol depletion alters the amount of mature
      SREBP, leading to the regulation of sterol-responsive gene expression.

PMID- 11590227
TI  - A rapid screening procedure for cholesterol and dehydrocholesterol by
      electrospray ionization tandem mass spectrometry.
AB  - The mono-(dimethylaminoethyl) succinyl (MDMAES) ester is a new derivative for
      rapid, mild, and sensitive electrospray ionization tandem mass spectrometry (ESI
      MS/MS) analysis of cholesterol and dehydrocholesterol. It is an order of
      magnitude more sensitive than the previous most practical alternative, the N
      methylpyridyl ether derivative. The MDMAES derivative was used to develop a rapid
      screening procedure for the biochemical diagnosis of Smith-Lemli-Opitz syndrome
      (SLOS) by measuring the dehydrocholesterol/cholesterol ratio in plasma (5 microl)
      and plasma spotted onto filter paper. Details of the synthesis of
      [25,26,26,26,27,27,27-(2)H7]-7-dehydrocholesterol, used as a standard for
      quantitation, are included. The measurement of total sterols as MDMAES esters,
      after base hydrolysis of plasma, afforded a dehydrocholesterol/cholesterol ratio
      of 0.05-2.95 for SLOS patient samples (n = 5) compared with 0.001-0.003 for
      normal adult controls (n = 20). Direct hexane extraction of plasma without base
      hydrolysis enabled the measurement of free sterols with a total sample analysis
      time of <1 h. The free dehydrocholesterol/cholesterol ratio was 0.10-4.47 for
      SLOS patient samples (n = 5) and 0.003-0.011 for normal adult controls (n = 20).

PMID- 11590228
TI  - A simple assay for a human serum phospholipase A2 that is associated with high
      density lipoproteins.
AB  - Phospholipase A2 (PLA2) activity is usually assayed with expensive radioactive or
      chromogenic substrates unsuitable for performing large numbers of assays. We have
      designed a simple microplate assay for human serum PLA2 using the chromogenic
      substrate 4-nitro-3-octanoyloxy-benzoic acid. Using this substrate, serum PLA2
      activity was similar to that measured with the previously characterized
      chromogenic phospholipid substrate 1,2-bis-heptanoylthio-glycerophosphocholine.
      However, the assay described here appears to be more sensitive. The mean PLA2
      activity in serum from healthy volunteers (n = 30) measured by this assay was
      10.4 +/- 1.6 micromol x h(-1) x ml(-1). The assay is reproducible and is suitable
      for the analysis of large numbers of samples in a clinical setting. We have also
      demonstrated that 94% of the PLA2 activity in normal human serum is associated
      with high-density lipoproteins and that serum PLA2 activity is positively
      correlated with the lipoprotein parameters total triglyceride (P < 0.0001), total
      cholesterol (P < 0.0001), and atherogenic index (P = 0.008). The serum PLA2
      activity was calcium dependent and was inhibited by the serine protease inhibitor
      3,4-dichloroisocoumarin (EC(50) = 0.4 mM). The PLA2 activity characterized here
      is unlikely to be due to plasma platelet-activating factor acetylhydrolase or low
      molecular weight His-Asp sPLA2, and may represent a new sPLA2 type.

PMID- 11590229
TI  - Let's talk! Different ways to communicate science in the lab. By Caveman.

PMID- 11590230
TI  - Assembly of the epidermal cornified cell envelope.

PMID- 11590233
TI  - The post-doc's view.

PMID- 11590232
TI  - Alan wolffe (1959-2001).

PMID- 11590234
TI  - The interface of receptor trafficking and signalling.
AB  - The intimate relationship between receptor trafficking and signalling is
      beginning to reveal its secrets. Receptor endocytosis provides a mechanism for
      attenuation of signalling by transfer of receptors to degradative compartments.
      However, it can also determine signalling output by providing a different
      combination of downstream effectors at endocytic compartments compared with the
      plasma membrane. Rab5, Hrs and Cbl, are three examples of proteins that can
      influence both tyrosine kinase receptor trafficking and signalling pathways. By
      operating at this intersection, they are well placed to couple these aspects of
      cell function. Each element of the Rab5 GTPase cycle is influenced by signal
      transduction events, which will correspondingly influence recruitment of effector
      proteins and receptor distribution. Hrs and Cbl, which both undergo tyrosine
      phosphorylation in response to growth factor stimulation, are believed to
      influence receptor sorting in the early endosome and engage in multiple
      interactions, which may play a direct role in signalling cascades.

PMID- 11590235
TI  - Post-transcriptional gene silencing in plants.
AB  - Post-transcriptional gene silencing (PTGS) in plants is an RNA-degradation
      mechanism that shows similarities to RNA interference (RNAi) in animals. Indeed,
      both involve double-stranded RNA (dsRNA), spread within the organism from a
      localised initiating area, correlate with the accumulation of small interfering
      RNA (siRNA) and require putative RNA-dependent RNA polymerases, RNA helicases and
      proteins of unknown functions containing PAZ and Piwi domains. However, some
      differences are evident. First, PTGS in plants requires at least two genes--SGS3
      (which encodes a protein of unknown function containing a coil-coiled domain) and
      MET1 (which encodes a DNA-methyltransferase)--that are absent in C. elegans and
      thus are not required for RNAi. Second, all Arabidopsis mutants that exhibit
      impaired PTGS are hypersusceptible to infection by the cucumovirus CMV,
      indicating that PTGS participates in a mechanism for plant resistance to viruses.
      Interestingly, many viruses have developed strategies to counteract PTGS and
      successfully infect plants--for example, by potentiating endogenous suppressors
      of PTGS. Whether viruses can counteract RNAi in animals and whether endogenous
      suppressors of RNAi exist in animals is still unknown.

PMID- 11590236
TI  - A specific targeting signal directs Runx2/Cbfa1 to subnuclear domains and
      contributes to transactivation of the osteocalcin gene.
AB  - Key components of DNA replication and the basal transcriptional machinery as well
      as several tissue-specific transcription factors are compartmentalized in
      specialized nuclear domains. In the present study, we show that determinants of
      subnuclear targeting of the bone-related Runx2/Cbfa1 protein reside in the C
      terminus. With a panel of C-terminal mutations, we further demonstrate that
      targeting of Runx2 to discrete subnuclear foci is mediated by a 38 amino acid
      sequence (aa 397-434). This nuclear matrix-targeting signal (NMTS) directs the
      heterologous Gal4 protein to nuclear-matrix-associated Runx2 foci and enhances
      transactivation of a luciferase gene controlled by Gal4 binding sites.
      Importantly, we show that targeting of Runx2 to the NM-associated foci
      contributes to transactivation of the osteoblast-specific osteocalcin gene in
      osseous cells. Taken together, these findings identify a critical component of
      the mechanisms mediating Runx2 targeting to subnuclear foci and provide
      functional linkage between subnuclear organization of Runx2 and bone-specific
      transcriptional control.

PMID- 11590237
TI  - The ZW10 and Rough Deal checkpoint proteins function together in a large,
      evolutionarily conserved complex targeted to the kinetochore.
AB  - The zeste-white 10 (zw10) and rough deal (rod) genes of Drosophila both encode
      kinetochore components, and mutations in either gene greatly increase the
      missegregation of sister chromatids during mitosis. Here, we present genetic,
      cytological and biochemical evidence for a close, evolutionarily conserved
      relationship between the ROD and ZW10 proteins. We show that the phenotypes
      caused by disruption of either gene's function are similar in Drosophila and in
      C. elegans. No additive effects are observed in zw10; rod double null mutants. In
      flies, the two proteins always colocalize and, moreover, require each other for
      their recruitment to the mitotic apparatus. The human ROD and ZW10 homologs also
      colocalize on HeLa cell kinetochores or kinetochore microtubules throughout most
      but not all of mitosis. Finally, we show that in both Drosophila and human cells,
      ROD and ZW10 are in fact physically associated, and in Drosophila these proteins
      are together constituents of a large (700-900 kDa), soluble macromolecular
      complex.

PMID- 11590238
TI  - Roles of the cytoplasmic and transmembrane domains of syntaxins in intracellular
      localization and trafficking.
AB  - Syntaxins are target-soluble N-ethylmaleimide-sensitive factor-attachment protein
      receptors (t-SNAREs) involved in docking and fusion of vesicles in exocytosis and
      endocytosis. Many syntaxin isoforms have been isolated, and each one displays a
      distinct intracellular localization pattern. However, the signals that drive the
      specific intracellular localization of syntaxins are poorly understood. In this
      study, we used indirect immunofluorescence analysis to examine the localization
      of syntaxin chimeras, each containing a syntaxin transmembrane domain fused to a
      cytoplasmic domain derived from a different syntaxin. We show that the
      cytoplasmic domains of syntaxins 5, 6, 7 and 8 have important effects on
      intracellular localization. We also demonstrate that the transmembrane domain of
      syntaxin 5 is sufficient to localize the chimera to the compartment expected for
      wild-type syntaxin 5. Additionally, we find that syntaxins 6, 7 and 8, but not
      syntaxin 5, are present at the plasma membrane, and that these syntaxins cycle
      through the plasma membrane by virtue of their cytoplasmic domains. Finally, we
      find that di-leucine-based motifs in the cytoplasmic domains of syntaxins 7 and 8
      are necessary for their intracellular localization and trafficking via distinct
      transport pathways. Combined, these results suggest that both the cytoplasmic and
      the transmembrane domains play important roles in intracellular localization and
      trafficking of syntaxins.

PMID- 11590239
TI  - Dynamics of integrin clustering at focal contacts of endothelial cells studied by
      multimode imaging microscopy.
AB  - Human umbilical vein endothelial cells were stained with FITC-labeled anti
      beta(1) integrin antibody and plated on a glass cover slip to elucidate the
      mechanism of integrin clustering during focal contact formation. The process of
      integrin clustering was observed by time-lapse total-internal-reflection
      fluorescence microscopy, which can selectively visualize the labeled integrins at
      the basal surface of living cells. The clustering of integrins at focal contacts
      started at 1 hour after plating and individual clusters kept growing for
      approximately 6 hours. Most integrin clusters (approximately 80%) elongated
      towards the cell center or along the cell margin at a rate of 0.29+/-0.24 microm
      minute(-1). Photobleaching and recovery experiments with evanescent illumination
      revealed that the integrins at the extending tip of the clusters were supplied
      from the intracellular space. Simultaneous time-lapse imaging of exocytosis of
      integrin-containing vesicles and elongating focal contacts showed that most
      exocytosis occurred at or near the focal contacts followed by their elongation.
      Double staining of F-actins and integrins demonstrated that stress fibers were
      located near the integrin clusters and that intracellular punctate integrins were
      associated with these stress fibers. These results suggest that the clustering of
      integrins is mediated by actin-fiber-dependent translocation of integrins to the
      extending tip of focal contacts.

PMID- 11590240
TI  - The Ccz1 protein interacts with Ypt7 GTPase during fusion of multiple transport
      intermediates with the vacuole in S. cerevisiae.
AB  - Previously we have shown that the Saccharomyces cerevisiae CCZ1 (YBR131w) gene
      encodes a protein involved in protein trafficking. Deletion of this gene leads to
      fragmentation of the vacuole typical of the class B vps mutants. Genetic and
      biochemical data indicated that Ccz1p is required for fusion of various transport
      intermediates with the vacuole. Here we present data indicating that CCZ1 is a
      close partner of the YPT7 gene, which encodes Rab GTPase and is required for
      fusion of transport vesicles to vacuole and homotypic vacuole fusion. We isolated
      extragenic suppressors of CCZ1 deletion. All these suppressors belong to one
      complementation group and correspond to mutated alleles of the YPT7 gene. The
      mutated residues are located in two Ypt7p domains responsible for guanine
      binding. These data suggest that Ccz1p and Ypt7p interact physically.
      Coimmunoprecipitation experiments provide direct evidence that this indeed is the
      case. A possible mechanism of Ccz1p action is discussed.

PMID- 11590241
TI  - Adenovirus-Cre-mediated recombination in mammary epithelial early progenitor
      cells.
AB  - The transplantation of primary mammary epithelial cells after adenovirus-Cre
      mediated recombination provides a new approach for the study of specific gene
      function during mammary gland development and in breast cancer. Most mammary
      gland-specific promoters identified to date are regulated by lactogenic hormones.
      They are expressed predominantly in lobuloalveolar cells during pregnancy and
      lactation, but not during early stages of ductal morphogenesis in the mammary
      epithelial cell progenitors, which are primarily implicated in tumorigenesis. In
      transgenic mice these promoters will continually or repeatedly express Cre
      depending on the hormonal environment precluding the definition of cell lineages.
      To circumvent these limitations, we have taken advantage of the unique
      regenerative capacity of mammary epithelium to reconstitute a mammary gland in an
      epithelium-cleared fat pad in conjunction with transient Cre expression using
      recombinant adenovirus in primary cultures. This approach was validated using
      mice carrying reporter constructs that exclusively express the LacZ gene after
      Cre-mediated deletion of a floxed DNA fragment. These studies demonstrated that,
      following recombination, cells that are marked as genetically manipulated
      contribute to the reconstitution of the mammary gland. The presence of beta
      galactosidase-expressing cells in serial transplants of the primary outgrowths
      indicated that early progenitor or stem cells were successfully targeted. With
      the increased availability of floxed alleles, this approach should greatly
      facilitate the study of gene function during early stages of mammary gland
      development and in breast cancer.

PMID- 11590242
TI  - Control of the nuclear-cytoplasmic partitioning of annexin II by a nuclear export
      signal and by p11 binding.
AB  - This study investigated mechanisms controlling the nuclear-cytoplasmic
      partitioning of annexin II (AnxII). AnxII and its ligand, p11, were localized by
      immunofluorescence to the cytoplasmic compartment of U1242MG cells, with minimal
      AnxII or p11 detected within nuclei. Similarly, GFP-AnxII and GFP-p11 chimeras
      localized to the endogenous proteins. Likewise, GFP-AnxII(1-22) was excluded from
      nuclei, whereas GFP-AnxII(23-338) and GFP alone were distributed throughout the
      cells. Immunoprecipitation and biochemical studies showed that GFP-AnxII did not
      form heteromeric complexes with endogenous p11 and AnxII. Thus, the AnxII N-tail
      is necessary and sufficient to cause nuclear exclusion of the GFP fusion protein
      but this does not involve p11 binding. A nuclear export signal consensus sequence
      was found in the AnxII 3-12 region. The consensus mutant GFP-AnxII(L10A/L12A)
      confirmed that these residues are necessary for nuclear exclusion. The nuclear
      exclusion of GFP-AnxII(1-22) was temperature-dependent and reversible, and the
      nuclear export inhibitor leptomycin B (LmB) caused GFP-AnxII or overexpressed
      AnxII monomer to accumulate in nuclei. Therefore, AnxII monomer can enter the
      nucleus and is actively exported. However, LmB had little effect on the
      localization of AnxII/p11 complex in U1242MG cells, indicating that the complex
      is sequestered in the cytoplasm. By contrast, LmB treatment of v-src-transformed
      fibroblasts caused endogenous AnxII to accumulate in nuclei. The LmB-induced
      nuclear accumulation of AnxII was accelerated by pervanadate and inhibited by
      genistein, suggesting that phosphorylation promotes nuclear entry of AnxII. Thus,
      nuclear exclusion of AnxII results from nuclear export of the monomer and
      sequestration of AnxII/p11 complex, and may be modulated by phosphorylation.

PMID- 11590243
TI  - mAKAP and the ryanodine receptor are part of a multi-component signaling complex
      on the cardiomyocyte nuclear envelope.
AB  - The physical association of regulatory enzymes and ion channels at relevant
      intracellular sites contributes to the diversity and specificity of second
      messenger-mediated signal transduction in cells. mAKAP is a scaffolding protein
      that targets the cAMP-dependent protein kinase A and phosphodiesterase type 4D3
      to the nuclear envelope of differentiated cardiac myocytes. Here we present data
      that the mAKAP signaling complex also includes nuclear envelope-resident
      ryanodine receptors and protein phosphatase 2A. The ryanodine receptor is the
      major cardiac ion channel responsible for calcium-induced calcium release from
      intracellular calcium ion stores. As demonstrated by a combination of
      immunohistochemistry and tissue fractionation, mAKAP is targeted specifically to
      the nuclear envelope, whereas the ryanodine receptor is present at both the
      sarcoplasmic reticulum and nuclear envelope intracellular membrane compartments.
      At the nuclear envelope, a subset of cardiac ryanodine receptor is bound to mAKAP
      and via the association with mAKAP may be regulated by protein kinase A-mediated
      phosphorylation. By binding protein kinase A and ryanodine receptor, mAKAP may
      serve as the scaffold for a cAMP- and calcium ion-sensitive signaling complex.

PMID- 11590244
TI  - alphaT-catenin: a novel tissue-specific beta-catenin-binding protein mediating
      strong cell-cell adhesion.
AB  - Cadherins are major cell-cell adhesion proteins whose cytoplasmic domains bind to
      catenin proteins. Strong intercellular adhesion depends on linkage of the
      cadherin/catenin complex to the actin cytoskeleton via alpha-catenin. To date, it
      is not clear how different cell types achieve the variable strength of cell-cell
      adhesion clearly needed in a multicellular organism. Here, we report the cloning
      and molecular characterization of alphaT(testis)-catenin, a novel human cDNA
      encoding a protein with homology to both human alphaE(epithelial)-catenin and
      alphaN(neural)-catenin. Although originally discovered in testis, alphaT-catenin
      is expressed in other tissues, the highest levels being observed in heart.
      Immunohistochemical analysis showed human alphaT-catenin localization at
      intercalated discs of cardiomyocytes and in peritubular myoid cells of testis. In
      cells transfected with alphaT-catenin cDNA, interaction with beta-catenin was
      demonstrated by co-immunoprecipitation. Transfection of alpha-catenin-deficient
      colon carcinoma cells recruited E-cadherin and beta-catenin to cell-cell contacts
      and functional cadherin-mediated cell-cell adhesion was restored in this way.
      Moreover, compaction of these cells was at least as prominent as in the case of
      cells expressing endogenous alphaE-catenin. We propose that alphaT-catenin is
      necessary for the formation of stretch-resistant cell-cell adhesion complexes, in
      particular, muscle cells.

PMID- 11590245
TI  - Cloning and expression of the putative aggregation factor from the marine sponge
      Geodia cydonium.
AB  - Sponges (phylum Porifera) have extensively been used as a model system to study
      cell-cell interaction on molecular level. Recently, we identified and cloned the
      putative aggregation receptor (AR) of the sponge Geodia cydonium, which interacts
      in a heterophilic way with the aggregation factor (AF) complex. In the present
      study, antibodies against this complex have been raised that abolish the adhesion
      function of the enriched sponge AF, the AF-Fraction 6B. Using this antibody as a
      tool, a complete 1.7 kb long cDNA, GEOCYAF, could be isolated from a cDNA library
      that encodes the putative AF. Its deduced aa sequence in the N-terminal section
      comprises high similarity to amphiphysin/BIN1 sequences found in Protostomia and
      Deuterostomia. However, the C-terminal portion of the sponge sequence lacks the
      SH3 domain characteristic for amphiphysin/BIN1. The polypeptide with a calculated
      size of 47 kDa was expressed in Escherichia coli. The recombinant, soluble 36 kDa
      putative AF was prepared and found to compete with the AF complex-associated
      adhesion protein of the AF-Fraction 6B for the binding sites at the cell surface.
      Furthermore, the recombinant putative AF was recognized by the antibody used to
      screen the cDNA library by western blotting. In addition, there is evidence that
      the recombinant putative AF binds to the G. cydonium galectin. It is concluded
      that the putative G. cydonium AF--a further autapomorphic molecule characteristic
      for Metazoa--binds to the AR present on the cell surface in association with the
      homologous galectin.

PMID- 11590246
TI  - Revealing the unseen: the organizer region of the nucleolus.
AB  - We carried out a high-resolution ultrastructural analysis of the nucleolus in
      mouse P815 cells by combining specific DNA and RNA staining, anti-fibrillarin
      immunolabeling, contrast enhancement by energy filtering TEM and phosphorus
      mapping by ESI to visualize nucleic acids. We demonstrated that specifically
      contrasted DNA, fibrillarin and phosphorus overlap within the nucleolar dense
      fibrillar component. Moreover, we describe a 'DNA cloud' consisting of an inner
      core of DNA fibers (fibrillar center) and a periphery made of extremely thin
      fibrils overlapping the anti-fibrillarin immunolabeling (dense fibrillar
      component). This highly sensitive approach has allowed us to demonstrate, for the
      first time, the exact distribution of DNA within the decondensed interphase
      counterpart of the NOR, which includes both the fibrillar center and the dense
      fibrillar component.

PMID- 11590247
TI  - Alterations in an IRE1-RNA complex in the mammalian unfolded protein response.
AB  - IRE1 proteins mediate cellular responses to accumulation of malfolded proteins in
      the endoplasmic reticulum in the yeast and mammalian unfolded protein responses.
      A sensitive in vivo u.v. crosslinking assay showed that IRE1 proteins are
      intimately associated with RNA in mammalian cells. The IRE1-associated RNA
      fragments recovered by this assay were different in stressed and unstressed
      cells. The amount of RNA associated with IRE1 that could be revealed by end
      labeling with T4 kinase was greater in IRE1-containing complexes isolated from
      stressed cells. Furthermore, the RNA fragments recovered from complexes found in
      stressed cells were shorter than those from unstressed cells, revealing a dynamic
      change in the IRE1-RNA complex during the UPR. Formation of the complex between
      IRE1 and RNA was dependent on both the kinase and endonuclease domains of IRE1,
      and involved pre-existing RNA species. When viewed in the context of the known
      importance of Ire1p-HAC1 mRNA interactions to the yeast unfolded protein
      response, these findings suggest that full-length mammalian IRE1s also engage RNA
      molecules as downstream effectors.

PMID- 11590249
TI  - Anaemia in end-stage renal disease: pathophysiological considerations.
AB  - Anaemia is a frequent complication of many diseases but the mechanisms that link
      reduced blood oxygen content to the long-term consequences of anaemia are
      incompletely understood. The maintenance of oxygen supply to the tissues during
      anaemia involves complex cardiovascular adaptations, including an increase in
      cardiac output, reduced peripheral resistance and increased oxygen extraction
      from haemoglobin (Hb). In addition, hypoxia-inducible factors are associated with
      the transcriptional activation of genes involved in adaptive mechanisms that
      increase oxygen delivery and provide alternative metabolic pathways. The complex
      pathophysiology of chronic kidney disease alters the adaptations to anaemia in
      uraemic patients. The increased cardiac output induced by anaemia is associated
      with left ventricular hypertrophy and cardiac disease in renal patients.
      Alterations in endothelial cell function, common in renal disease, may diminish
      endothelium-induced vasodilatation, increase the risk of atherosclerosis and
      impair angiogenesis. Many potential reasons for erythropoietin-induced
      hypertension in uraemic patients have been postulated, including increased blood
      viscosity as haematocrit rises, a reversal of hypoxic vasodilatation, increased
      blood volume that is not compensated by haemodialysis, ultrafiltration and
      impaired nitric oxide synthesis, preventing vascular relaxation in response to
      increased blood viscosity. In view of this impaired vascular reactivity, rapid
      increases in haematocrit should be avoided during epoetin treatment. As the
      interaction between anaemia and uraemia is very complex, it is not possible to
      derive the optimal Hb concentration for individual patients by using simple
      physiological or pathophysiological models and there is a need for good
      randomized controlled clinical trials to address this issue.

PMID- 11590250
TI  - Individualizing target haemoglobin concentrations--tailoring treatment for renal
      anaemia.
AB  - Despite the publication of National Kidney Foundation and European Best Practice
      Guidelines, there is still uncertainty among nephrologists regarding the optimum
      target haemoglobin (Hb) concentration for patients treated with erythropoietin.
      For most patients, the target Hb concentration is 11-12 g/dl, resulting in only
      partial correction of anaemia. However, there is a link between subnormal Hb
      concentration and the development of cardiovascular disease. Thus, it may be more
      beneficial to normalize Hb, although this has to be balanced against the concern
      that full correction of anaemia may result in adverse effects, such as
      hypertension and progression of renal disease. There is increasing evidence that
      it may be appropriate to treat each patient individually, and to tailor treatment
      according to a number of physiological and lifestyle variables, avoiding higher
      Hb concentrations in certain patient groups (such as those with cardiac
      problems). This was supported by the results of a survey of nephrologists and
      specialists in the field of renal anaemia. It was generally agreed that a higher
      target Hb concentration (12-14 g/dl) might be appropriate for a fit, young
      patient with no significant co-morbidity, whereas a lower target Hb (10-12 g/dl)
      might be appropriate for an elderly patient with multiple medical problems. In
      conclusion, guidelines for target Hb in the US and Europe are probably not
      applicable to all patients. It is important that renal anaemia patients are
      considered as individuals, and their treatment tailored accordingly. It is time
      to establish evidence-based criteria for individualizing renal anaemia treatment.

PMID- 11590251
TI  - Flexible dosing schemes for recombinant human erythropoietin--lessons from our
      daily practice.
AB  - The availability of recombinant human erythropoietin (rh-Epo) has revolutionized
      the treatment of renal anaemia. Subcutaneous (s.c.) administration of rh-Epo
      offers significant advantages over the intravenous (i.v.) route, and numerous
      studies have demonstrated its efficacy and tolerability when administered two or
      three times weekly. Most of these studies showed a significant reduction in rh
      Epo dosage requirements with s.c. administration compared with the i.v. route,
      offering clear benefits in terms of reduced costs. In addition, s.c.
      administration is more convenient and flexible than i.v. administration, and is
      recommended by European and US guidelines. Dosing frequency of rh-Epo is also an
      important issue in clinical practice, particularly when customizing therapy to
      meet individual patient needs. A few small-scale studies have shown comparable
      efficacy and tolerability of different s.c. dosing frequencies. Recently, a
      comprehensive randomized controlled trial has shown that once weekly s.c. epoetin
      beta effectively manages anaemia in haemodialysis patients, even in patients
      requiring a high dose. Once weekly dosing of s.c. epoetin beta adds greater
      flexibility and an improved capacity to tailor dosing frequency to patient needs.
      This reduces clinic time for patients who do not self-administer and, together
      with improved convenience of new formulations and delivery systems, has the
      potential to improve compliance and encourages self-administration.

PMID- 11590252
TI  - Patient education: can it maximize the success of therapy?
AB  - The majority of patients with chronic renal insufficiency (CRI) have only limited
      knowledge of their condition. Various studies of the benefits of patient
      education programmes have shown that educated patients have a reduced incidence
      of emergency dialysis compared with control patients. Additionally, more educated
      patients are able to start dialysis as an outpatient rather than in hospital. An
      education programme also allowed a greater number of blue-collar workers to
      remain employed after starting dialysis. The US National Pre-End-Stage Renal
      Disease (pre-ESRD) Education Initiative, which is currently in progress, aims to
      educate a large number of pre-ESRD patients on kidney function, renal failure,
      dialysis, and transplant options. Preliminary results suggest that the initiative
      influences the choice of dialysis and that, regardless of race, age, and co
      morbidities, the incidence of peritoneal dialysis could be increased in ESRD
      patients in the US. Education on other components of therapy may also influence
      patient outcomes. In the management of renal anaemia, improved education, and
      advances in the delivery systems available for administration of erythropoietin
      may be important factors in improving patient compliance and maximizing the
      success of treatment. Thus, education of patients early in the course of CRI
      offers many potential benefits for patients and healthcare professionals,
      including improved treatment outcomes, reduced anxiety, greater prospect for
      continued employment, improved timing for the start of dialysis, and a greater
      opportunity for intervention to delay disease progression.

PMID- 11590253
TI  - Hyporesponsiveness to recombinant human erythropoietin.
AB  - The introduction of recombinant human erythropoietin (rh-Epo, epoetin) as a
      treatment for the anaemia of renal failure has transformed the management of this
      condition. Nevertheless, a significant number of patients fail to respond. There
      are many different possible causes of inadequate response to epoetin. Iron
      deficiency, whether absolute or functional, is considered to be the most
      important, and it is widely accepted that maintaining adequate iron levels
      reduces rh-Epo dosage requirement and improves efficacy in haemodialysis
      patients. Infection and inflammation have been shown to influence responsiveness
      to rh-Epo by disrupting iron metabolism and eliciting the release of cytokines
      that inhibit erythropoiesis. Another factor for consideration is severe
      hyperparathyroidism, which can lead to a reduced number of responsive erythroid
      progenitor cells. Inadequate dialysis can also negatively impact on rh-Epo
      therapy, and aluminium overload interferes with iron metabolism and reduces the
      efficacy of rh-Epo. Deficiencies in vitamin B(12), folic acid and potentially
      vitamin C can all reduce the efficacy of treatment with rh-Epo. Optimizing
      patient response to rh-Epo therapy, therefore, requires consideration of many
      factors, some well established and others that are more controversial, and the
      list continues to grow with the identification of new factors.

PMID- 11590254
TI  - Dialysis: its role in optimizing recombinant erythropoietin treatment.
AB  - Although iron deficiency is probably the most important factor affecting response
      to recombinant erythropoietin (Epo, epoetin), other factors are of significance,
      including dialysis adequacy. Additionally, water treatment and distribution,
      sterilizants and the quality of the dialysate in terms of trace elements
      (particularly chloramine) are of importance in relation to erythropoiesis
      inhibition. Microbiological or pyrogenic contamination can cause or aggravate
      anaemia in haemodialysis patients, and the impact of enhanced production of
      cytokines should be taken into consideration. By removing small and (possibly)
      medium/large molecules, adequate dialysis is of paramount importance in
      correcting anaemia and optimizing epoetin therapy. The biocompatibility of
      dialysis membranes and flux are other important factors. As yet unknown uraemic
      toxins may suppress erythropoiesis and contribute towards the development of
      anaemia. It is reasonable to hypothesize that, because anaemia improves after the
      start of dialysis with cellulose membranes, low molecular weight erythropoiesis
      inhibitors are involved, as well as medium/large molecular weight inhibitors,
      which are removed by more permeable membranes. However, in highly selected,
      adequately dialysed patients without iron or vitamin depletion, the effects of
      dialysis membrane type on haematological parameters and epoetin efficacy are
      smaller than might be expected from the results of uncontrolled studies.
      Improvement in anaemia has been observed using on-line haemofiltration,
      haemodiafiltration, and sterile dialysate. The results of prospective, randomized
      trials examining the impact of these factors on anaemia and the effectiveness of
      epoetin treatment are eagerly awaited.

PMID- 11590255
TI  - The role of inflammation in the anaemia of end-stage renal disease.
AB  - Chronic inflammation is a common feature of end-stage renal disease (ESRD) that
      is gaining increasing attention as a major cause of morbidity and mortality. It
      is well established that ESRD per se carries a heightened risk of inflammatory
      disorders and other co-morbid conditions, but it should also be pointed out that
      dialysis treatment per se can bring additional risk factors for inflammation,
      such as impure dialysate or bio-incompatible membranes. Inflammation has recently
      been associated with atherosclerosis and malnutrition in ESRD, and this link has
      led to the development of the malnutrition, inflammation, atherosclerosis (MIA)
      hypothesis. This describes a syndrome whereby raised levels of pro-inflammatory
      cytokines (such as IL-1, IL-6 and TNF-alpha) are a common link between
      malnutrition, inflammation and atherosclerosis. Also, anaemia appears to be an
      important element linking elevated cytokine levels with poor patient outcomes.
      Several mechanisms for cytokine-induced anaemia have been proposed, including
      intestinal bleeding, impaired iron metabolism and suppression of bone marrow
      erythropoiesis and erythropoietin production. These effects suggest that pro
      inflammatory cytokines may also be an important cause of lack of response to
      recombinant human erythropoietin (rh-Epo) therapy. In the light of this putative
      role of pro-inflammatory cytokines, anti-cytokine agents may prove useful to
      optimize efficacy of rh-Epo in anaemic chronic renal failure patients. Other
      potential therapeutic strategies include minimizing exposure to causes of
      inflammation from various co-morbid conditions, such as persistent infections and
      chronic heart failure.

PMID- 11590256
TI  - Anaemia in chronic renal disease: lessons learned since Seville 1994.
AB  - Cardiovascular disease is the major cause of death among patients with end-stage
      renal disease, accounting for almost half of all fatalities. In recent years much
      progress has been made in understanding the pathogenesis of cardiovascular
      disease in the uraemic population. Anaemia is a consistent finding in chronic
      renal disease, affecting up to 90% of patients, and the central role of anaemia
      in the development of cardiovascular dysfunction is now well established. A
      significant proportion of patients have established cardiovascular complications
      on initiation of dialysis, raising the possibility of early correction of anaemia
      as a strategy for preventing cardiovascular co-morbidities among renal patients.
      Randomized, controlled trials have shown that normalization of haemoglobin (Hb)
      with recombinant erythropoietin (rh-Epo) is of no cardiovascular benefit in
      haemodialysis patients with symptomatic heart failure, ischaemic heart disease,
      or severe left ventricular dilatation, although suggestive evidence exists for
      benefits at earlier stages of cardiac disease. Results from large-scale clinical
      trials are required to clarify the effects of early anaemia correction on
      mortality and cardiovascular function, as well as appropriate treatment targets
      in different patient populations. The potential exists for higher Hb levels to
      extend patient survival through cardioprotective effects.

PMID- 11590257
TI  - Advances in nephrology: successes and lessons learnt from diabetes mellitus.
AB  - The introduction of recombinant erythropoietin (Epo, epoetin) has resulted in a
      shift in focus from the treatment to the prevention of anaemia. This shift in
      treatment goals has provided nephrologists with the challenge of implementing
      preventative strategies in clinical practice. While this area of nephrology is
      still developing, a lot can be learned from the methods applied by clinicians
      involved in the prevention of other diseases, particularly non-insulin-dependent
      (type 2) diabetes mellitus. The prevention of type 2 diabetes has become a major
      aim of healthcare providers globally due to the epidemic proportions of the
      disease. In order to reverse this worrying trend, diabetologists have had to
      develop effective management strategies based upon their current knowledge.
      Nephrologists must now adopt a similar approach if the increasing threat from
      diabetic nephropathy is to be reversed. This should include strict normotension,
      the prescribing of angiotensin-converting enzyme (ACE) inhibitors, administration
      of lipid-lowering agents, and the near-normalization of anaemia with epoetin.
      However, the implementation of treatment strategies alone is unlikely to be
      sufficient. Indeed, an effective programme of education is required to ensure
      that patients understand the seriousness of their condition and remain compliant
      with treatment. Similarly, educating the general public may help to reduce the
      burden of type 2 diabetes and the subsequent problems associated with the
      disease, including renal disease.

PMID- 11590258
TI  - The rationale for early management of chronic renal insufficiency.
AB  - Several strategies are available to delay progression of renal disease and the
      development of associated co-morbidities. Hypertension is a strong independent
      risk factor for end-stage renal disease (ESRD) and there is consensus that blood
      pressure (BP) management is an important aspect of care in patients with chronic
      renal insufficiency (CRI). Clinical studies have shown that angiotensin
      converting enzyme (ACE) inhibitors have renoprotective properties, independent of
      their antihypertensive effects, which can delay the onset of ESRD. Studies have
      also shown that intensive therapy of both type 1 and type 2 diabetes patients, to
      give near normal blood glucose concentrations, can reduce the incidence of
      progressive clinical proteinuria and may, therefore, protect against ESRD.
      Additionally, data are emerging that treatment of renal anaemia with epoetin can
      reduce mortality and delay the onset of dialysis in CRI patients, but these
      encouraging results need to be confirmed in large prospective studies. In
      conclusion, control of BP and hyperglycaemia, as well as use of ACE inhibitors
      and anaemia treatment, all have potential in delaying the progression of CRI or
      improving patient outcomes. If benefit is proven in future studies, these
      strategies will be most effective if implemented early in the course of CRI.

PMID- 11590259
TI  - Identification of patients and risk factors in chronic kidney disease--evaluating
      risk factors and therapeutic strategies.
AB  - Three strategies can help delay chronic kidney disease (CKD) progression: early
      identification of patients, modification of risk factors, and implementation of
      the best interventions. Early identification of patients requires accurate
      screening tools. As serum creatinine is an unreliable marker of kidney
      dysfunction, clinicians should focus on the glomerular filtration rate or other
      markers of true kidney function. Clinicians should also be aware of other
      indicators of abnormal kidney function, such as anaemia, acidosis, and increases
      in parathyroid hormone level. Additionally, both clinicians and patients should
      be aware of the "non-modifiable" and "modifiable" risk factors for CKD. Non
      modifiable risk factors include age, gender, race, diabetes, and genetic make-up,
      while modifiable risk factors include elevated blood pressure and blood glucose,
      proteinuria, anaemia, metabolic disturbances, and dyslipidaemia. Patients should
      be particularly aware of the risk factors common to both cardiac and kidney
      disease, such as hypertension, proteinuria, anaemia, and (possibly) dyslipidaemia
      and diabetes. A single centre study demonstrated that inclusion in a
      multidisciplinary CKD clinic programme produced the greatest increases in time to
      renal replacement therapy, haemoglobin levels, and epoetin treatment usage at
      initiation of dialysis in comparison with standard nephrology care or no care.
      Two years after starting dialysis, the number of deaths was lowest, and the
      number of patients who had received a transplant or were still on dialysis was
      highest, in the CKD clinic-treated group. These results confirm those of previous
      studies, which showed that timely referral to a multidisciplinary team for
      management prior to dialysis decreases the risk of adverse patient outcomes. This
      suggests that a multidisciplinary, collaborative, proactive approach increases
      the likelihood of early identification of CKD patients and risk factor
      modification. However, further evidence-based demonstrations of success are
      required, showing benefit to both patients and health care systems.

PMID- 11590260
TI  - Chronic kidney disease: why is current management uncoordinated and suboptimal?
AB  - Morbidity and mortality associated with chronic kidney disease (CKD) is higher
      than that of the normal population, and the incidence of end-stage renal disease
      (ESRD) continues to increase. Several factors contribute to the uncoordinated and
      suboptimal management of CKD, including the attitude and behaviour of
      nephrologists, referring physicians and patients, and economic constraints on
      healthcare systems. Late referral of at-risk patients to specialist care is an
      area of particular concern, as this denies nephrologists adequate opportunity to
      prevent progression of CKD and associated complications such as anaemia. Due to
      the ageing population and advances in technology, the costs of treating CKD and
      ESRD continue to escalate and represent another barrier to the delivery of
      optimal care. Optimizing the care provided to CKD patients requires a coordinated
      approach to the management of the condition. Closer collaboration and improved
      communication across specialities is important for the timely referral of
      patients and for efficient utilization of available resources. A
      multidisciplinary approach may facilitate patient identification and improve the
      management of CKD.

PMID- 11590261
TI  - Emerging infectious diseases in Hong Kong.

PMID- 11590262
TI  - A profile of anaesthesia trainees in Hong Kong.
AB  - OBJECTIVES: To examine the demographics, professional background, progress, and
      aspirations of anaesthesia trainees in Hong Kong. DESIGN: Anonymous questionnaire
      consisting of 56 items grouped into the areas of demographics, and anaesthetic
      and postanaesthetic training. Eight of the items were open questions. Descriptive
      analyses were undertaken for the closed items. SETTING: Hong Kong College of
      Anaesthesiologists, Hong Kong. PARTICIPANTS: All trainees. MAIN OUTCOME MEASURES:
      Demographic data, aspects of training, supervision, working environment, career
      aspirations, job satisfaction, and morale. RESULTS: The response rate was 77%.
      The various problems highlighted by respondents included the need for more input
      and feedback into individual training programmes, the lack of senior support, and
      the need for more relevant and examination-orientated courses and workshops.
      Unsatisfactory aspects of the specialty reported were the lack of control over
      work routines, relationships with surgeons, boredom, and the poor public image of
      the specialty. Eighty-four percent of respondents reported having reasonable to
      good job satisfaction. CONCLUSIONS: Ongoing benefits could be derived from
      enhancing communication between trainees and the Hong Kong College of
      Anaesthesiologists, through appropriate channels for trainee feedback.

PMID- 11590263
TI  - Obstructive sleep apnoea in children with adenotonsillar hypertrophy: prospective
      study.
AB  - OBJECTIVE: To determine clinical and baseline polysomnographic data on
      obstructive sleep apnoea secondary to adenotonsillar hypertrophy in Hong Kong
      Chinese children. DESIGN: Prospective study. SETTING: University teaching
      hospital, Hong Kong. PARTICIPANTS: Fifty children (35 boys and 15 girls)
      suspected to have obstructive sleep apnoea were recruited between January 1999
      and December 1999. MAIN OUTCOME MEASURES: Symptoms questionnaire,
      electrocardiogram, chest radiograph, and full-night polysomnography. RESULTS: All
      patients had symptoms suggestive of obstructive sleep apnoea. None were found to
      have clinical evidence of cor pulmonale. Forty-five (90%) of 50 children had
      obstructive sleep apnoea with a respiratory disturbance index of greater than
      five. Central and mixed apnoeas were rare. Tonsil size did not correlate with the
      severity of obstructive sleep apnoea. CONCLUSION: Symptoms and signs suggestive
      of obstructive sleep apnoea can lead to a high detection rate and confirmation of
      obstructive sleep apnoea by polysomnography.

PMID- 11590264
TI  - The effect of vertebral rotation of the lumbar spine on dual energy X-ray
      absorptiometry measurements: observational study.
AB  - OBJECTIVE: To estimate how axial rotation of lumbar vertebrae quantitatively
      affects bone mineral density, as measured by dual energy X-ray absorptiometry in
      the anteroposterior plane. DESIGN: Observational study. SETTING: University
      teaching hospital, Hong Kong. PATIENTS: Cadaver lumbar vertebrae (L2 to L4) were
      removed from four adults. MAIN OUTCOME MEASURES: Using dual energy X-ray
      absorptiometry, the bone mineral content, bone area, and bone mineral density
      were measured in the neutral position and with vertebral axial rotation in
      increments of 7.5 degrees, up to a maximum of 45 degrees. RESULTS: Correlation
      analysis showed a significant positive correlation between the degree of rotation
      and measured bone area, a significant negative correlation between degree of
      rotation and bone mineral density measurements, but no significant correlation
      between degree of rotation and measured bone mineral content. The measured bone
      area increased approximately 24% and the bone mineral density decreased
      approximately 19% when the vertebrae were rotated by 45 degrees. CONCLUSIONS:
      These results suggest that for patients with rotational deformity of the spine,
      such as scoliosis, measurements of lumbar spine bone mineral content by dual
      energy X-ray absorptiometry is not affected, while bone mineral density
      measurements are not reliable.

PMID- 11590265
TI  - Universal screening of human immunodeficiency virus infection in pregnant women
      in Hong Kong: prospective study.
AB  - OBJECTIVE: To evaluate universal screening with an opt-out approach of pregnant
      women for human immunodeficiency virus infection. DESIGN: Prospective study.
      SETTING: Regional hospital, Hong Kong. PATIENTS: All women booked or delivered in
      Kwong Wah Hospital from 1 January 1999 to 30 November 1999 were recruited. MAIN
      OUTCOME MEASURES: Numbers of women who received the human immunodeficiency virus
      antibody screening test, refused the test (and the reasons why), tested positive,
      and tested positive with confirmation by immunoblot study. RESULTS: A total of
      5597 women were recruited and 5459 screening tests performed in this study. Of
      the 16 screened positive cases, three were confirmed by immunoblot study. The
      overall acceptance rate for the test was 97.5%. The acceptance rate among the
      5191 women recruited through the hospital's booking clinic was not significantly
      different from that among the 406 women who did not go through the hospital's
      booking clinic (97.6% versus 96.6%). CONCLUSION: Universal screening of pregnant
      women for human immunodeficiency virus infection with an opt-out approach is
      practical, feasible, and clinically acceptable in Hong Kong.

PMID- 11590266
TI  - Anaesthetic clinical indicators in public hospitals providing anaesthetic care in
      Hong Kong: prospective study.
AB  - OBJECTIVES: To assess the quality of anaesthetic services as defined in the six
      anaesthetic clinical indicators against preset standards and to identify risk
      factors for adverse events in the recovery room. DESIGN: Prospective study.
      SETTING: All public hospitals providing anaesthetic care in Hong Kong. PATIENTS:
      Eighteen thousand, seven hundred and fifty-nine patients receiving elective or
      emergency anaesthesia administered by anaesthetists from June 1998 to July 1998.
      MAIN OUTCOME MEASURES: Patient demographics, American Society of
      Anesthesiologists status, category and nature of operation, presence of
      preoperative anaesthetic visit in ward, type of anaesthesia, reasons for a
      recovery room stay of more than a 2-hour duration, intubation to relieve
      respiratory distress in the recovery room, presence of hypothermia in the
      recovery room for operations lasting more than 2 hours, and dental or ocular
      injuries attributable to anaesthesia. RESULTS: There are two major findings from
      this study. Firstly, a high incidence of hypothermia in the recovery room was
      reported. Secondly, a greater risk of prolonged stay in the recovery room was
      identified for patients older than 65 years, major operations, and anaesthetic
      techniques using combined general and regional anaesthesia. CONCLUSION: The six
      anaesthetic clinical indicators reflected the provision of anaesthetic care in
      public hospitals in Hong Kong. Good compliance to the preset standard of the
      anaesthetic clinical indicators was achieved during the study period.

PMID- 11590268
TI  - Mechanisms of cell death and treatment prospects in motor neuron disease.
AB  - Scientific evidence is emerging to indicate that motor neuron injury in motor
      neuron disease may reflect a complex interplay between genetic factors, oxidative
      stress, and imbalance of the glutamatergic excitatory control of motor neurons,
      which may result in damage to critical target proteins and organelles. The
      relative importance of these factors is likely to vary in different subgroups of
      patients. Protein aggregation may play a role in some forms of motor neuron
      injury, and the eventual demise of motor neurons may occur by a programmed cell
      death pathway. Advances in symptomatic therapy for patients with motor neuron
      disease include the development of specialist clinics, with input from
      multidisciplinary teams, as well as hospice care in the late stages of the
      disease. A number of recent therapeutic trials of potential neuroprotective drugs
      have been conducted, including antiglutamate, antioxidant, and neurotrophic
      agents. To date, only the antiglutamate agent riluzole has been shown to
      reproducibly prolong the survival of patients with motor neuron disease. Future
      therapy in motor neuron disease is likely to include a 'cocktail' of
      neuroprotective compounds to interfere with several molecular pathway that lead
      to neuronal injury. In using therapeutic strategies aimed towards retarding or
      arresting motor neuron disease, close attention will need to be paid to quality
      of life issues.

PMID- 11590267
TI  - Outcomes and complications of thyroid surgery: retrospective study.
AB  - OBJECTIVE: To study the outcome and complications of thyroid surgery. DESIGN:
      Retrospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Three
      hundred and twelve patients (266 women and 46 men) underwent thyroid surgery
      between January 1994 and December 1999. MAIN OUTCOME MEASURES: Complications of
      thyroidectomy for various thyroid diseases according to surgical technique used.
      RESULTS: Capsular dissection gradually became a more popular surgical technique:
      33% and 58% in the first and second halves of the study period respectively
      (P<0.001). The overall rate of permanent vocal cord palsy was 2%. Near-total
      thyroidectomy became the preferred surgical treatment for toxic goitre over the
      study period. The incidence of recurrent hyperthyroidism was reduced from 21% to
      7% (P>0.1, not significant). The incidence of hypoparathyroidism was
      approximately 30% after thyroidectomy for cancer. CONCLUSION: Capsular dissection
      is increasingly utilised in thyroid surgery. Low complication rates can be
      achieved after thyroidectomy for benign diseases. Hypoparathyroidism, however, is
      a relatively common complication after surgery for thyroid cancer.

PMID- 11590269
TI  - Abdominal pain after endoscopic intervention.

PMID- 11590270
TI  - Opinion survey of Hong Kong private primary care doctors about cervical
      screening.
AB  - The policy and practice of Hong Kong private primary care doctors regarding
      cervical screening were investigated by way of two different questionnaires sent
      to comparable random survey samples. The overall response rate was 60.8%
      (313/515). Both sexes of eligible doctors believed that cervical smears were
      effective and important, but only 40.2% (47/117) of male doctors performed the
      test compared with 65.5% (19/29) of female doctors. Those doctors who do not
      perform the test themselves usually refer their patients elsewhere. The small
      proportion of private doctors offering cervical smears may reduce opportunities
      for women who need them. Over 80% of private doctors recommended annual smears
      despite local recommendations for 3-yearly tests, while graduates from western
      countries were more likely to recommend longer intervals. Since the proportion of
      women in Hong Kong having Papanicolaou tests is still low, effort should focus on
      providing smears for more women, rather than repeated annual testing of those who
      already participate.

PMID- 11590271
TI  - Distally based sural neurocutaneous flaps for ankle and heel ulcers.
AB  - This study assessed the use of sural neurocutaneous flaps to repair chronic
      ulcers in difficult-to-cover areas around the ankle and heel. Follow-up of the 14
      patients included in this study ranged from 6 months to 3 years after their
      operation. Total flap loss occurred in two patients, both of whom had rheumatoid
      arthritis complicated by vasculitis. Partial flap loss occurred in three
      patients; all were heel ulcers. Additional skin grafting procedures were required
      to cover their ulcers. A lateral malleolus ulcer in a patient with rheumatoid
      arthritis recurred after 1 year and had to be covered with a free parascapular
      flap. The sural neurocutaneous flap is thus a reliable means of resurfacing
      ulcers in the ankle and heel region. It requires no sacrifice of major peripheral
      vessels and may be a useful alternative for patients with poor peripheral pulses.
      Its use in the presence of vasculitis, however, needs further refinement.

PMID- 11590272
TI  - Variant Creutzfeldt-Jakob disease in Hong Kong.
AB  - A 34-year-old Chinese woman who had lived in the United Kingdom in the 1980s was
      admitted to hospital in Hong Kong because of a 7-month history of progressive
      neurological deterioration. Initially, she complained of heartburn and
      paraesthesia of the hands and feet. She then developed slowness of speech and
      gait, and was noted to be forgetful and irritable. In January 2001, she was
      brought back to Hong Kong for treatment. On admission in May she was dysarthric,
      ataxic, and dystonic. Magnetic resonance imaging showed high signals in both
      thalami suggestive of variant Creutzfeldt-Jakob disease. Other investigations,
      including electroencephalogram and lumbar puncture, were unremarkable. A tonsil
      biopsy showed the presence of prions. This patient's presentation is typical of
      the variant Creutzfeldt-Jakob disease cases that have been reported since 1996.
      Because of her residential history, we conclude that this is an imported case
      from the United Kingdom.

PMID- 11590273
TI  - Triiodothyronine augmentation for the treatment of depression in substance
      misusers unresponsive to tricyclic antidepressants.
AB  - We report on two substance misusers with depression resistant to tricyclic
      antidepressant treatment who responded to triiodothyronine augmentation. The
      management of resistant depression, augmentation strategies with particular
      reference to triiodothyronine, and the possible mechanism of action of
      triiodothyronine are discussed.

PMID- 11590274
TI  - Septic metastatic endophthalmitis complicating Klebsiella pneumoniae liver
      abscess in a non-diabetic Chinese man.
AB  - Septic metastatic endophthalmitis is a rare but serious disease. Endophthalmitis
      arising from Klebsiella pneumoniae liver abscess has been reported with diabetes
      mellitus as a major associated condition, but is rarely seen in patients without
      diabetes. A non-diabetic patient with liver abscess complained of right eye
      discomfort and floaters 3 days after admission. Both blood and liver aspirate
      cultured Klebsiella pneumoniae. The patient was treated initially with systemic
      and subconjunctival antibiotics followed by intravitreal antibiotics with
      successful visual salvation. Previous reports from the literature showed poor
      visual outcome despite treatment and delayed recognition was often the cause.
      Clinicians should be alert to endophthalmitis whenever a patient with Klebsiella
      pneumoniae liver abscess complains of ocular symptoms. Urgent ophthalmological
      assessment should be sought.

PMID- 11590275
TI  - Severe mitral regurgitation due to mitral valve prolapse associated with Bland
      White-Garland syndrome.
AB  - Bland-White-Garland syndrome refers to the rare congenital cardiac abnormality
      whereby the left coronary artery arises from the pulmonary artery. The natural
      history of this condition is highly variable, ranging from death in early infancy
      to asymptomatic adult survival. It is sometimes diagnosed in adults with mitral
      regurgitation thought to be of ischaemic origin. We report a case of a 29-year
      old man with Bland-White-Garland syndrome and concomitant mitral valve prolapse,
      and review the literature on the appropriate investigations and management of
      this abnormality. Recognition and diagnosis of this condition is important
      because of the potentially life-threatening complications, which may be prevented
      by surgical intervention.

PMID- 11590276
TI  - Unmasking of thyrotoxicosis during anaesthesia.
AB  - Two cases of subclinical and undiagnosed thyrotoxicosis that presented with
      unexplained tachycardia during surgery are described. Differential diagnosis and
      logistics in the management of patients presenting with tachycardia, with or
      without fever during anaesthesia are discussed. It is emphasised that when
      encountering unexplained tachycardia during anaesthesia, thyrotoxicosis must be
      suspected. Investigations for thyrotoxicosis must be carried out in the
      postoperative period.

PMID- 11590277
TI  - Intracerebral haemorrhage and Qigong.
AB  - We report on a 65-year-old woman who presented with acute right-sided weakness
      because of an intracerebral (thalamic) haemorrhage. As a Qigong enthusiast with a
      long-standing history of hypertension, she developed a stroke syndrome soon after
      practising Qigong one morning. Following neurological recovery, the patient
      exhibited erratic blood pressure responses while practising Qigong, despite the
      fact that resting blood pressure was normal. The haemodynamic responses to
      exercise are discussed and a review of the therapeutic implications of practising
      Qigong is presented.

PMID- 11590278
TI  - Laparoscopic repair of incisional hernia.
AB  - A 75-year-old man developed an incisional hernia over the upper abdomen following
      a wedge resection of a gastric stromal tumour in 1996. This is the first
      published report of a successful repair of an incisional hernia via a
      laparoscopic intraperitoneal on-lay technique using GORE-TEX DualMesh material in
      Hong Kong. Compared with conventional open repair of incisional hernia, long
      incisions and wound tension are avoided using the laparoscopic approach. This
      translates into a reduced risk of wound-related complications and facilitates
      recovery. In selected cases, minimally invasive surgery is a safe technique for
      the repair of incisional hernias.

PMID- 11590279
TI  - Smoking makes Marlboro cowboy 'unfit'.

PMID- 11590280
TI  - Non-melanoma skin cancer in Hong Kong.

PMID- 11590281
TI  - A case of phenacetin-induced skin cancer in Hong Kong.

PMID- 11590282
TI  - Doctor-patient relationship: the importance of the patient's perceptions.

PMID- 11590283
TI  - Non-atherosclerotic aorto-arterial thrombosis: A study of 30 cases at autopsy.
AB  - BACKGROUND: Aorto-arterial thrombosis is very often associated with
      atherosclerotic and/or aneurysmal changes. Thrombosis, unrelated to these changes
      is infrequent. AIMS: To evaluate the clinical presentation and aetiopathogenesis
      of aorto-arterial thrombosis, unrelated to atherosclerosis and aneurysms.
      SUBJECTS AND METHODS: A retrospective study of 30 autopsied cases of non
      atherosclerotic and non-aneurysmal aorto-arterial thrombosis collected over a
      period of 14 years was carried out. RESULTS: There were 23 males and seven
      females and majority presented in the third to fourth decades of life with
      clinical features of acute abdomen or lower limb gangrene. Abdominal aorta as the
      site of thrombosis was observed in 46.5% cases. The causes were attributed to
      hypercoagulable states and changes in the aortic wall. No aetiology could be
      identified in 5 patients (16.6%. Associated tuberculosis was seen in six cases.
      CONCLUSIONS: Non-atherosclerotic aortic thrombosis is a heterogeneous group of
      disorders. Young and even elderly patients with symptoms related to abdominal
      ischaemia or peripheral vascular disease should be investigated thoroughly for
      hypercoagulable states and aortic pathology.

PMID- 11590284
TI  - Is internal podalic version a lost art? Optimum mode of delivery in transverse
      lie.
AB  - AIM: To study the changing trend in the delivery of transverse lie, and its
      effect on neonatal outcome, in a developing country. SUBJECTS AND METHOD: This is
      a retrospective study involving records of 12 years of all patients with
      transverse lie. Neonatal outcome of births by internal podalic version (IPV) and
      lower segment caesarean section (LSCS) were compared. RESULTS: In the first six
      years, 37.3% of transverse lie underwent IPV and 62.7%, LSCS. In the next six
      years, 15.8% underwent IPV and 84.2%, LSCS. 87.7% and 12.3% of live babies were
      delivered by LSCS and IPV respectively. 52% of the live born IPV were discharged
      compared to 95% of LSCS babies. Neonatal outcome was best when IPV was performed
      on second twin. CONCLUSION: IPV has a role in the delivery of second twin, pre
      viable and dead babies.

PMID- 11590285
TI  - Knowledge, attitude and practices of parents of children with febrile convulsion.
AB  - CONTEXT: Parental anxiety and apprehension is related to inadequate knowledge of
      fever and febrile convulsion. AIMS: To study the knowledge, attitude, and
      practices of the parents of children with febrile convulsions. SETTINGS AND
      DESIGN: Prospective questionnaire based study in a tertiary care centre carried
      over a period of one year. SUBJECTS AND METHODS: 140 parents of consecutive
      children presenting with febrile convulsion were enrolled. STATISTICAL ANALYSIS
      USED: Chi-square test. RESULTS: 83 parents (59.3%) could not recognise the
      convulsion; 90.7% (127) did not carry out any intervention prior to getting the
      child to the hospital. The commonest immediate effect of the convulsion on the
      parents was fear of death (n= 126, 90%) followed by insomnia (n= 48, 34.3%),
      anorexia (n= 46, 32.9%), crying (n= 28, 20%) and fear of epilepsy (n= 28, 20%).
      Fear of brain damage, fear of recurrence and dyspepsia were voiced by the fathers
      alone (n= 20, cumulative incidence 14.3%). 109 (77.9%) parents did not know the
      fact that the convulsion can occur due to fever. The long-term concerns included
      fear of epilepsy (n= 64, 45.7%) and future recurrence (n= 27, 19.3%) in the
      affected child. For 56 (40%) of the parents every subsequent episode of fever was
      like a nightmare. Only 21 parents (15%) had thermometer at home and 28 (20%) knew
      the normal range of body temperature. Correct preventive measures were known only
      to 41 (29.2%). Awareness of febrile convulsion and the preventive measures was
      higher in socio-economic grade (P< 0.05). CONCLUSIONS: The parental fear of fever
      and febrile convulsion is a major problem with serious negative consequences
      affecting daily familial life.

PMID- 11590286
TI  - Severe acute renal failure in malaria.
AB  - BACKGROUND: We have noticed a recent rise in the incidence and severity of acute
      renal failure (ARF) in malaria. AIM: To study the incidence, severity and outcome
      of ARF in malaria. SETTING AND DESIGN: It is a retrospective analysis of data of
      one year from a tertiary medical centre in a metropolitan city. MATERIALS AND
      METHODS: Patients with ARF and smear positive malaria were evaluated. STATISTICAL
      ANALYSIS: Results were expressed as mean, range and standard deviation. RESULTS:
      Out of 402 detected smear positive malaria, 24 had ARF. Eighteen were of the age
      group 21-40 years. Plasmodium falciparum (PF) was detected in 16, Plasmodium
      vivax in three, and mixed infection in five. Non-oliguric ARF was seen in 14.
      Eighteen showed severe ARF (Serum creatinine >5 mg%). Twenty-two patients needed
      dialysis. Prolonged ARF lasting for 2-6 weeks was seen in eight. Seventeen
      patients recovered completely, while seven showed fatal combination of
      disseminated intravascular coagulation (DIC), acute respiratory distress syndrome
      (ARDS), severe ARF and PF malaria. No response was seen to chloroquine and
      artesunate given alone and twenty patients required quinine. CONCLUSION: ARF
      necessitating dialysis was seen in 92% of patients with ARF in malaria. PF
      infection, severe ARF, DIC and ARDS were poor prognostic factors. Resistance was
      noted to both chloroquine and artesunate.

PMID- 11590287
TI  - Clinical and aetiological profile of early onset diabetes mellitus: data from a
      tertiary care centre in the Indian subcontinent.
AB  - BACKGROUND: Type 2 diabetes mellitus (DM) in youth is emerging as a serious
      clinical entity and its incidence has increased over the years. AIM: To analyse
      the causes of DM in the age group of <40 years of age. SETTINGS AND DESIGN:
      Tertiary care centre; retrospective analysis of data from January 1990 to
      December 1999. SUBJECTS AND MATERIAL: Analysis of data of all the subjects of DM
      in whom disease started before the 40th birthday. RESULTS: 724 subjects were
      detected to have diabetes mellitus before their 40th birthday. Of these, 205 had
      Type 1, 174 had Type 2 and 48 had fibrocalculous pancreatic diabetes. Males
      outnumbered in Type 1 and fibrocalculous pancreatic diabetes while as females in
      Type 2 diabetes mellitus. Chronic complications were more common in Type 2
      diabetes mellitus. CONCLUSION: Type 2 diabetes mellitus is becoming an important
      cause of diabetes in subjects with onset of disease at younger age.

PMID- 11590288
TI  - Pulmonary nocardiosis in human immunodeficiency virus infection: a tuberculosis
      mimic.
AB  - Patients with human immunodeficiency virus (HIV) infection are prone to develop
      pulmonary infections like nocardiosis. It is often misdiagnosed as pulmonary
      tuberculosis since the manifestations are similar. A twenty-seven years old male
      presented with fever, cough with expectoration and weight loss for two months.
      Chest radiograph showed opacity in the right mid zones. Sputum smears were
      negative for acid fast bacilli (AFB) and revealed gram positive branching
      filamentous organisms resembling Nocardia species. Subsequently, Nocardia was
      grown on sputum culture. HIV antibody was positive by ELISA test. He was treated
      with co-trimoxazole. If sputum is repeatedly tested negative for AFB in the
      setting of radiological suspicion of tuberculosis, testing for Nocardia species
      should be considered in the HIV-infected patients.

PMID- 11590289
TI  - Angioembolisation in vaginal vascular malformation.
AB  - Vaginal arteriovenous malformations are rare entities and their most common
      presentation is vaginal haemorrhage. This case report describes a 22-year-old
      woman who presented at 20 weeks of gestation with slow growing soft and tender
      swelling at anterior vaginal wall. Diagnosis was confirmed as vaginal vascular
      malformation on contrast enhanced magnetic resonance imaging. The mass did not
      subside after delivery and patient developed dyspareunia. It was successfully
      treated by angioembolisation using polyvinyl alcohol particles. Angioembolisation
      being safe and effective should be the treatment of first choice for symptomatic
      vaginal vascular malformation.

PMID- 11590290
TI  - Haemorrhagic pneumonitis: A rare presentation of leptospirosis.
AB  - Leptospirosis is an uncommon zoonosis. As a systemic disease, it presents itself
      by multisystem involvement. Pulmonary involvement with leptospirosis often is
      manifested by respiratory symptoms; but pneumonia commonly is not a prominent
      clinical manifestation of the illness. We report a case of leptospiral pneumonia
      in which pulmonary manifestations were primary clinical features of the illness.
      The prompt resolution of chest x-ray on institution of treatment is noteworthy.

PMID- 11590291
TI  - Hepatic hydatid cyst rupturing into sub-diaphragmatic space and pericardial
      cavity.
AB  - A ten-year-old male child presented with a large hepatic hydatid cyst which
      ruptured into the sub-diaphragmatic space and pericardial cavity, giving rise to
      a pericardial effusion. This communication between the hydatid cyst and the
      pericardium was documented on computerised tomographic scan of the chest and
      abdomen. The cyst was aspirated carefully and then enucleated. There was an
      associated right-sided reactionary pleural effusion. The pericardial effusion and
      pleural effusion resolved on albendazole therapy and did not require surgical
      intervention.

PMID- 11590292
TI  - Doctor.com: Why should a doctor have his own website?

PMID- 11590293
TI  - Evolution of Medical Education Technology Unit in India.

PMID- 11590294
TI  - ICH harmonized tripartite guideline: Guideline for Good Clinical Practice.

PMID- 11590295
TI  - Prolapsing anterior urethral polyp.

PMID- 11590296
TI  - Myxoid liposarcoma of the spermatic cord.

PMID- 11590297
TI  - Tuberculosis of pubic symphysis presenting with hypogastric mass.

PMID- 11590298
TI  - Neurobiological correlates of panic disorder and agoraphobia.
AB  - Panic Disorder and agoraphobia offer considerable diagnostic and management
      challenges, particularly in general practice. We describe a typical case of panic
      disorder in a young adult. The recent advances in our understanding of brain
      functions can be used to explain to a certain extent the biologic basis of panic
      disorder. A hypothetical model integrating current views on panic disorder and
      agoraphobia has been proposed. The management principles including the role of
      cognitive therapy and pharmacotherapy have been discussed.

PMID- 11590299
TI  - Rehabilitation of cancer patients.
AB  - With the developments in cancer treatment, more and more patients are surviving
      their disease. However, very little emphasis is being placed to rehabilitate
      these cancer survivors. Ignorance, social structure, stigma attached in seeking
      psychological help, and poor communication skills of oncology staff all
      contribute to poor rehabilitative efforts. The priority of governmental agencies
      and health efforts to fight rampant communicable diseases, malnutrition, maternal
      health, and the frequent natural calamities, puts rehabilitation movements in the
      back seat. Treatment and prevention of disability and its rehabilitation requires
      comprehensive and multidisciplinary approach. There is an urgent need to promote
      physical and psychological rehabilitation.

PMID- 11590300
TI  - Percutaneous conservative management of emphysematous pyelonephritis.

PMID- 11590301
TI  - Management of nephrolithiasis in crossed renal ectopia.

PMID- 11590302
TI  - Mahatma Gandhi Institute of Medical Sciences.

PMID- 11590303
TI  - History of psychiatry in India.

PMID- 11590304
TI  - Rofecoxib: a new selective COX-2 inhibitor.

PMID- 11590305
TI  - A multiposition brain holder: a versatile appliance for microneurosurgical
      laboratory.

PMID- 11590306
TI  - Dactylogyridean monogeneans of the siluriform fishes of the Old World.
AB  - This is a catalogue and discussion of the known dactylogyridean monogenean genera
      of siluriform fishes of the Old World. Of a total of 38 nominal genera, only 19
      are considered valid. Seventeen of these 19 genera are currently in the
      Ancyrocephalidae (containing the Ancyrocephalinae and Ancylodiscoidinae), whilst
      the other two (Neocalceostoma and Neocalceostomoides) are in the
      Neocalceostomatidae. The 17 genera are Anchylodiscus, Ancylodiscoides,
      Bagrobdella, Bifurcohaptor, Bychowskyella, Chauhanellus, Cornudiscoides,
      Hamatopeduncularia, Mizelleus, Paraquadriacanthus, Pseudancylodiscoides,
      Protoancylodiscoides, Quadriacanthus, Schilbetrema, Schilbetrematoides,
      Synodontella and Thaparocleidus. Clariotrema Long, 1981 and Neobychowskyella Ma,
      Wang & Li, 1983 are considered synonyms of Bychowskyella Akhmerov, 1952,
      Anacornuatus Dubey, Gupta & Agarwal, 1992 is considered a synonym of
      Quadriacanthus Paperna, 1961, Mizellebychowskia Gupta & Sachdeva, 1990 is
      considered a synonym of Neocalceostoma Tripathi, 1959 and Hargitrema Tripathi,
      1959 is treated as a synonym of Hamatopeduncularia Yamaguti, 1953. It is proposed
      that the Ancylodiscoidinae be raised to family status within the order
      Dactylogyridea to accommodate these 17 'ancyrocephalid' genera from siluriforms,
      together with Malayanodiscoides and Notopterodiscoides from notopterids. A key
      and the diagnostic characteristics of the 19 recognised dactylogyridean genera
      from catfishes plus two from notopterids, together with a list of species and
      synonyms, are included. New combinations made in this work are Thaparocleidus
      avicularia (Chen, 1987) n. comb., T. calyciflorus (Chen, 1987) n. comb., T.
      choanovagina (Luo & Lang, 1981) n. comb., T. dissimilis (Chen, 1988) n. comb., T.
      leiocassis (Reichenbach-Klinke, 1959) n. comb., T. meticulosa (Chen, 1987) n.
      comb., T. parasoti (Zhao & Ma, 1999) n. comb., T. persculpus (Chen, 1987) n.
      comb., T. valga (Chen, 1987) n. comb. and T. wulingensis (Yao & Wang, 1997) n.
      comb. [all from Silurodiscoides] and Bychowskyella glyptothoraci (Ma, Wang & Li,
      1983) n. comb. [from Neobychowskyella].

PMID- 11590307
TI  - The mesoparasitic genera of the Ergasilidae (Copepoda): with descriptions of new
      species of Paeonodes Wilson and Therodamas Kroyer.
AB  - One species of each of the three mesoparasitic ergasilid genera, Therodamas
      Kroyer, Mugilicola Tripathi and Paeonodes Wilson, is described in detail. The
      descriptions of P. subviridis n. sp. and Mugilicola bulbosus Tripathi are based
      on new material collected from Liza subviridis (Valenciennes) from Guam and
      India, respectively. The description of Therodamas frontalis n. sp. is based on
      material from Mugil cephalus L. in Brazil and the redescription of Therodamas
      serrani Kroyer is based on examination of syntype material. The geographical
      distributions of all three genera are summarised. Analysis of the phylogenetic
      relationships between species of these three genera indicates that Paeonodes and
      Mugilicola form a single clade and that Paeonodes, as currently constituted, is
      paraphyletic.

PMID- 11590308
TI  - Two new species of Acanthobothrium Beneden, 1849 (Tetraphyllidea:
      Onchobothriidae) from horn sharks in the Gulf of California, Mexico.
AB  - Between 1993 and 1996, 26 individuals of two species of horn sharks were
      collected from the upper Gulf of California and their spiral intestines examined
      for onchobothriid tapeworms. Heterodontus francisci was found to host
      Acanthobothrium puertecitense n. sp. Based on the criteria of Ghoshroy & Caira
      (2001), this is a Category 4 species (with >15 mm total length, >50 proglottids,
      >80 testes and a symmetrical ovary). It differs from the four Category 4 species
      previously reported from either the western Atlantic or eastern Pacific Oceans,
      including A. bajaense (emend.) which was described from H. francisci, in hook
      shape, total length, number of proglottids, number of testes and number of
      columns of vitelline follicles. H. mexicanus was found to host Acanthobothrium
      santarosaliense n. sp., which, based on the criteria of Ghoshroy & Caira (2001)
      is a Category 3 species (with >15 mm total length, >50 proglottids, >80 testes
      and an asymmetrical ovary). A. santarosaliense differs from the five Category 3
      species previously reported from either the western Atlantic or eastern Pacific
      Oceans in its size, euapolytic nature, lack of dark matrix from the bases of the
      hooks, hook-shape, and distribution and number of testes. In addition to the
      difference in ovarian symmetry, A. puertecitense possesses fewer testes, fewer
      proglottids, is a shorter worm, possesses a more anterior genital pore and
      vitelline follicles which extend further forward anteriorly than in A.
      santarosaliense. This represents the first report of onchobothriids from H.
      mexicanus and the first report of onchobothriids from H. francisci in the Gulf of
      California. The apparent host-specificity of both new species should be viewed
      with caution until a greater sample of host individuals of both species can be
      examined. The fact that both new tapeworm species are known only from the Gulf is
      also considered to be a preliminary result, given the small sample of host
      individuals examined from these regions to date. This brings the total number of
      species of Heterodontus known to host Acanthobothrium to four and the total
      number of Acanthobothrium species described from heterodontiform sharks to five.

PMID- 11590309
TI  - Probothriocephalus alaini n. sp. (Cestoda: Triaenophoridae) from the deep-sea
      fish Xenodermichthys copei in the North Atlantic Ocean.
AB  - Probothriocephalus alaini n. sp. is described from the intestine of the deep-sea
      fish Xenodermichthys copei (Gill) (Osmeriformes: Alepocephalidae) from the North
      Atlantic. It resembles most closely the type-species of Probothriocephalus, P.
      muelleri Campbell, 1977 described from Alepocephalus agassizi Goode & Bean
      (Alepocephalidae), but it differs in the distribution of the vitelline follicles
      that form two medially well-separated bands (versus almost circum-cortical in P.
      muelleri), in the shape of gravid proglottids that are elongate, much longer than
      wide (always wider than long in P. muelleri), in the size of the body (much
      larger in the latter species) and a somewhat different shape of the scolex
      (widely lanceolate versus elongate and tapering anteriorly in P. muelleri). Other
      congeneric species, described from deep-sea fish of different orders
      (Myctophiformes and Beryciformes), lack a distinct neck region, their eggs were
      reported to be non-operculate and they have much more pronounced external
      segmentation.

PMID- 11590312
TI  - The ethics of childbirth: are all roads leading to cesarean?

PMID- 11590314
TI  - Difficult airway in obstetric anesthesia: a review.
AB  - Failed intubation and ventilation are important causes of anesthetic-related
      maternal mortality. The purpose of this article is to review the complex issues
      in managing the difficult airway in obstetric patients. The importance of prompt
      and competent decision making in managing difficult airways, as well as a need
      for appropriate equipment is emphasized. Four case reports reinforce the
      importance of a systematic approach to management. The overall preference for
      regional rather than general anesthesia is strongly encouraged. The review also
      emphasizes the need for professional and experienced team cooperation between the
      obstetrician and the anesthesiologist for the successful management of these
      challenging cases. LEARNING OBJECTIVES: After completion of this article, the
      reader will be able to break down the complex issues in managing the difficult
      airway in the obstetric patient, outline the reasons for difficult intubations in
      pregnancy, and describe the evaluation used to predict a difficult intubation.

PMID- 11590315
TI  - A comprehensive approach to the menopause: so far, one size should fit all.
AB  - Although extensive studies have indicated that the benefits of hormone
      replacement therapy outweigh the risks, many women and health care providers have
      concerns about safety and side effects. Many alternative therapies are popular
      with patients, and menopausal women in the United States spent more than $600
      million in 1999 alone purchasing these therapies. Several of the more commonly
      used alternative therapies for the menopause are critically appraised in this
      article. For women who choose not to take estrogen, and for those who do, the
      additional benefits of calcium, vitamin D, exercise, stress reduction, and
      different dietary and lifestyle adaptations may enhance the quality of life as
      they age. Although they have the potential for being effective and safe options,
      there has been limited clinical research for the other alternative therapies.
      Gynecologists and other health care providers should be aware of the lack of
      evidence for the effectiveness of most of these therapies when they address
      patient's questions and concerns. Our information about alternative therapies
      will increase in the coming years. Ultimately, the growing number of available
      treatment choices will allow individualization of the treatment. Nevertheless,
      until prospective studies with prolonged follow-up are conducted to evaluate the
      risks and benefits of different alternative therapies, hormone replacement
      therapy, which is better studied, will remain the treatment of first choice, and
      "one size fits all" will continue to describe the management plan for most peri-
      and postmenopausal women at least in the near future. LEARNING OBJECTIVES: After
      completion of this article, the reader will be able to summarize the various
      alternatives to hormonal therapy for menopausal symptoms, describe the effects of
      phytoestrogens in the management of menopausal symptoms, and explain the origin
      and clinical use of the more common herbal therapies.

PMID- 11590316
TI  - Focus on primary care: evaluation, management, and treatment of obesity in women.
AB  - Obesity is the number one nutritional disorder in the developed world. It is now
      well recognized that obesity is a disease that represents a rapidly growing
      epidemic. It is often a lifelong problem that preferentially affects women.
      Modern science and medicine are just beginning to unravel the multifactorial
      pathophysiology of obesity. Current literature emphasizes the metabolic,
      hormonal, and behavioral interactions as well as genetic predisposition. This
      understanding has led to new recommendations for the management of the obese
      patient and to new pharmaceutical approaches for those at high risk. These risks
      include diabetes, cardiovascular disease, hypertension, gallbladder disease, and
      osteoarthritis. In addition, there are a number of reproductive health problems
      unique to obese women. Until recently, however, the evidence for benefit of
      weight loss was not clear. There are now numerous Category A data indicating
      significant benefit for weight loss as it affects multiple comorbidities It is,
      therefore, incumbent upon the providers of women's health care to assess patient
      risk and to offer resources, guidance, assistance, and reassurance to the
      overweight and obese patient as she embarks on a program of renewed health
      through weight loss. LEARNING OBJECTIVES: After completion of this article, the
      reader will be able to describe the classification of overweight and obesity,
      explain the pathophysiology of obesity, outline the evaluation and screening of
      the obese patient, and list potential therapeutic interventions for weight loss.

PMID- 11590317
TI  - An orthotopic model of ductal adenocarcinoma of the pancreas in severe combined
      immunodeficient mice representing all steps of the metastatic cascade.
AB  - INTRODUCTION: Clinically relevant animal models are needed to evaluate new
      therapeutic strategies against pancreatic adenocarcinoma, which is almost
      incurable by established treatment. AIMS: To establish and characterize a
      metastatic orthotopic transplant model for pancreatic ductal adenocarcinoma in
      severe combined immunodeficient (SCID) mice. METHODOLOGY: Human pancreatic ductal
      carcinoma cells, PancTu 1, were implanted either subcutaneously or orthotopically
      into the pancreas. RESULTS: After 4 weeks, orthotopic transplantation resulted in
      an extensive local tumor growth of an undifferentiated ductal adenocarcinoma with
      slight to moderate desmoplastic reaction. The tumor growth and spread resembled
      the situation in humans, including invasion into adjacent organs causing biliary
      and stomach obstruction. In addition, tumor metastases to regional lymph nodes of
      the pancreas, lung, liver, mesentery, and diaphragm, and attached to the kidneys,
      spleen, and reproductive organs were observed. In contrast, no invasion or
      metastases could be demonstrated by subcutaneous implanted PancTu I cells. Using
      immunohistochemical analysis, even single human tumor cells could be detected in
      blood vessels and metastatic organs, providing evidence that the orthotopic
      transplant model appropriately reflects the entire process of the metastatic
      cascade. CONCLUSION: This cancer model in SCID mice appears to be a powerful tool
      to investigate the identity of metastasis-associated genes and to evaluate
      preclinically the potency of novel antimetastatic agents in ductal adenocarcinoma
      of the pancreas.

PMID- 11590318
TI  - Integrin-mediated differentiation of a pancreatic carcinoma cell line is
      independent of FAK or MAPK activation levels.
AB  - INTRODUCTION: The extracellular matrix (ECM) plays a salient role for
      proliferation and differentiation of epithelial cells. It was demonstrated that
      cell-ECM interactions mediated through integrins control gene expression and the
      tissue phenotype even in malignant tumors. Alterations of the ECM are a key
      feature of ductal adenocarcinoma of the pancreas. AIMS: To examine the role of
      integrins and related signaling events for differentiation. METHODOLOGY AND
      RESULTS: We established an in vitro model for ECM-induced differentiation of
      poorly differentiated pancreatic carcinoma cells and found that a specific
      pattern of ECM proteins resembling basal laminas (matrigel) induces
      differentiation of the PaTu-II pancreatic carcinoma cell line to a ductal
      phenotype. Both beta1- and beta4-integrins are required for cellular
      differentiation. Integrin-associated signaling events include activation of pp125
      focal adhesion kinase (FAK) and mitogen-activated protein kinases (MAPKs) such as
      extracellular signal-regulated kinases (ERKs) and c-Jun NH2-terminal kinases
      (JNKs). However, beta1- and beta4-integrin-mediated differentiation of PaTu-II
      cells was independent from FAK, ERK, and JNK activation levels. Inhibition of
      MAPK kinases by PD98059 led to a reduction of proliferation but did not interfere
      with cellular differentiation of PaTu-II cells on matrigel. CONCLUSION: The
      integrin-mediated differentiation of PaTu-II cells is regulated and maintained
      through FAK- and MAPK-independent signal transduction pathways.

PMID- 11590319
TI  - Expression of p57/Kip2 protein in pancreatic adenocarcinoma.
AB  - INTRODUCTION: Evaluation of the biologic character of carcinomas requires
      understanding of cell cycle regulators. AIMS: To investigate p57 expression in
      human pancreatic adenocarcinoma and cyst adenoma. METHODOLOGY: We examined the
      expression of p57(Kip2), a member of the Cip/Kip family, in 45 pancreatic
      adenocarcinomas, 7 cystadenomas, and 7 chronic pancreatitis cases. RESULTS: The
      p57 labeling index (LI) in duct epithelia in chronic pancreatitis averaged 32.8+/
      8.3 and was significantly higher than in normal duct epithelia (18.8+/-6.6; p =
      0.0011). For the carcinoma, the LI averaged 46.0+/-20.9, which was significantly
      higher than that for normal duct epithelia (p < 0.0001) and cystadenoma (16.0
      11.2; p = 0.0007). However, it was significantly reduced in cases with stage IV
      disease (p = 0.0351), lymph node metastasis (p = 0.0003), larger size (p =
      0.0094), capsular invasion (p = 0.0462), lymphatic invasion (p = 0.0351), and
      cell proliferating activity (p = 0.0002). In multivariate analysis, p57 LI in
      pancreatic adenocarcinoma was independently linked to high proliferating activity
      (p = 0.0230). CONCLUSION: These results suggest that p57 plays a role in the
      hyperplastic change of the ducts in chronic pancreatitis and that pS7
      overexpression contributes to the downregulation of cell proliferation, and its
      decreased expression contributes to the progression of pancreatic adenocarcinoma.

PMID- 11590320
TI  - Tumor necrosis factor-related apoptosis-inducing ligand and its receptor
      expression and the pathway of apoptosis in human pancreatic cancer.
AB  - METHODOLOGY: The authors performed the reverse transcription-polymerase chain
      reaction (RT-PCR) in 17 cases of pancreatic ductal cell carcinoma (PDC) and five
      cases of normal pancreatic tissues to determine the expression of tumor necrosis
      factor -related apoptosis-inducing factor (TRAIL) and its five receptors in PDC.
      RESULTS: The expression of TRAIL and its receptors other than osteoprotegerin was
      found frequently in both PDC and normal tissues. whereas the expression of
      osteoprotegerin was detected only in PDC. The authors detected cancer cell death
      by TRAIL, ranging from 37% to 77% in all the PDC cell lines by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Hochest
      staining revealed that cell death was caused by apoptosis. Caspase-8 and caspase
      3 and poly (ADP-ribose) polymerase cleavage was activated within 2 hours after
      stimulation with 200 ng/mL TRAIL. CONCLUSION: These findings suggest a relation
      between osteoprotegerin expression and the biologic aggressiveness of PDC and the
      involvement of caspase-8 and caspase-3 activation in the TRAIL-mediated apoptosis
      pathway in PDC.

PMID- 11590321
TI  - Altered expression and localization of the tight junction protein ZO-1 in primary
      and metastatic pancreatic cancer.
AB  - INTRODUCTION: ZO-1 is a tight junction membrane protein that plays a critical
      role in cell-cell interaction, proliferation, and differ entiation. AIM: To
      localize and evaluate the expression of ZO-1 in the normal human pancreas, in
      pancreatic ductal adenocarcinoma (PDAC), and in chronic pancreatitis (CP).
      METHODOLOGY AND RESULTS: Northern and Western blot analysis revealed ZO-1
      expression in all six tested pancreatic cancer cell lines. Expression of ZO-1
      mRNA was increased sixfold in PDAC samples in comparison with normal samples (p =
      0.04). Confocal microscopy revealed the presence of ZO-1 in the apical and
      apicolateral areas of ductular cells in the normal pancreas. Similarly, in CP, ZO
      1 was localized at apical and apicolateral areas of small proliferating ductular
      cells and large metaplastic ducts. In PDAC, however, ZO-1 expression was observed
      irrespective of whether the cancer cells formed duct-like structures or exhibited
      a diffuse infiltrating pattern. Metastatic pancreatic cancer cells within lymph
      nodes displayed variable staining patterns, ranging from apical and apicolateral
      to a diffuse membranous staining. CONCLUSION: These observations suggest that ZO
      1 is overexpressed in PDAC and raise the possibility that this overexpression may
      confer a metastatic advantage to pancreatic cancer cells.

PMID- 11590322
TI  - Influence of octreotide on liver metastasis and hepatic lipid peroxidation in BOP
      induced pancreatic cancer in Syrian hamsters.
AB  - INTRODUCTION: In prospective clinical trials, octreotide improved quality of life
      and survival time in patients with pancreatic cancer. AIMS: To analyze whether
      octreotide modulates the hepatic oxygen radical metabolism and thus might
      decrease liver metastasis in an animal model of pancreatic cancer. METHODOLOGY:
      Syrian hamsters received 0.9% NaCl or N-nitrosobis(2-oxopropyl)amine (BOP) for 3
      months. Therapy was performed for 12 weeks by 0.9% NaCl or octreotide. Hamsters
      received a standard diet (3.5% fat) or were fed a high-fat diet (21.4% fat). In
      the 25th week, the pancreas and liver were examined macroscopically and
      histologically. The level of lipid peroxidation and activities of glutathione
      peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined
      intrahepatically. RESULTS: The number of liver metastases per animal and the size
      of liver metastases were increased by the high-fat diet, whereas they were
      decreased by octreotide. Octreotide increased activities of GSH-Px and SOD. The
      concentration of thiobarbituric acid reactive substances was increased by BOP and
      a high-fat diet and decreased by octreotide. CONCLUSION: Octreotide decreases the
      number and size of liver metastases in chemically induced pancreatic cancer in
      Syrian hamsters. This is accompanied by high hepatic GSH-Px and SOD activity and
      a low level of lipid peroxidation.

PMID- 11590323
TI  - Retinoic acid enhances the cytotoxic effects of gemcitabine and cisplatin in
      pancreatic adenocarcinoma cells.
AB  - INTRODUCTION: Retinoids, which are derivatives of vitamin A, are important
      factors involved in the control of biologic functions such as cell growth and
      differentiation, development, and carcinogenesis. We have shown previously that
      the naturally occurring retinoids all-trans-retinoic acid (ATRA) and 9
      cisretinoic acid (9cRA) induce growth inhibition followed by apoptosis in
      pancreatic adenocarcinoma cells in vitro. AIM: To evaluate the efficacy of
      retinoids in combination with the chemotherapeutic drugs gemcitabine and
      cisplatin. METHODOLOGY: In vitro growth inhibition and induction of apoptosis by
      different combinations of retinoids and cytotoxic drugs were studied by using the
      T3M-4 and BxPc-3 cell lines. For in vivo studies, T3M-4 cells were injected
      subcutaneously in nude mice. RESULTS: Pre-treatment of pancreatic adenocarcinoma
      cells with ATRA or 9cRA before the addition of the drugs resulted in significant
      reduction in cell number compared with treatment with the drugs alone. Pre
      treatment with 9cRA followed by gemcitabine or cisplatin alone also resulted in a
      strong increase in the percentage of cells undergoing programmed cell death, or
      apoptosis. Furthermore, there was an indication that the combination of ATRA and
      gemcitabine caused increased apoptosis in vivo. CONCLUSION: Our results clearly
      suggest the need for additional studies exploring the potential role of the
      combination of retinoids and gemcitabine in the management of pancreatic cancer.

PMID- 11590324
TI  - Epidermal growth factor induces cyclin D1 in human pancreatic carcinoma: evidence
      for a cyclin D1-dependent cell cycle progression.
AB  - INTRODUCTION: We recently showed that cyclin D1 is overexpressed in human
      pancreatic carcinoma cells, and that this overexpression correlates significantly
      with a poor prognosis. AIMS: To assess the interrelations of epidermal growth
      factor (EGF), EGF receptor (EGFR), and cyclin D1 in human pancreatic carcinoma.
      METHODOLOGY AND RESULTS: In pancreatic carcinoma cell lines (BxPC-3, AsPC-1),
      cell cycle analysis revealed an increase in cells in the S/G1 phase between 18
      and 30 hours after stimulation with 50 ng/mL EGF. Cyclin D1 mRNA increased after
      2 hours, corresponding to an increase in cyclin D1 protein, with the maximum
      level between 7.5 and 10 hours after stimulation, as demonstrated by Western blot
      analysis. We performed immunohistochemical analysis on 61 adenocarcinoma tissues
      for the expression of EGF, EGFR, and cyclin D1 and demonstrated an overexpression
      in the tumor cells in 51%, 54%, and 62.3%, respectively, whereas normal human
      pancreas stained negative for all of the three factors. Interestingly, EGF and
      EGFR expression correlated significantly with the cyclin D1 expression in human
      pancreatic tumor cells (p < 0.001 and p < 0.01, respectively). CONCLUSION: These
      results demonstrate that cyclin D1 overexpression in the tumor cells of
      pancreatic carcinoma tissue is at least partly dependent on the mitogenic effects
      of EGF signaling through the EGFR.

PMID- 11590325
TI  - Role of TGF-beta1, extracellular matrix, and matrix metalloproteinase in the
      healing process of the pancreas after induction of acute necrotizing pancreatitis
      using arginine in rats.
AB  - INTRODUCTION: Pancreatic tissues are almost completely restored to normal after
      an attack of acute pancreatitis, once the cause of the disease is removed.
      Transforming growth factor (TGF)-beta and extracellular matrix (ECM) are known to
      play an important role in the process of wound healing in pathologic diseases.
      Tissue repair is a process regulated by a balance between synthesis and
      degradation of ECM. AIMS: To elucidate the role of TGF-beta, ECM, and matrix
      metalloproteinase (MMP) in the process of regeneration occurring after acute
      necrotizing pancreatitis. METHODOLOGY: Acute necrotizing pancreatitis was induced
      by intraperitoneal injection of 500 mg/100 g body weight of L-arginine in male
      Wistar rats. Expression of TGF-beta1 and ECM messenger RNA (mRNA) was determined
      by Northern blot analysis, and that of MMP-1 and MMP-2 mRNA was examined by the
      reverse transcription polymerase chain reaction (RT-PCR). Immunoreactivity for
      ECM components, TGF-beta1, and MMP-2 in the pancreas was assessed by using a
      monoclonal antibody. RESULTS: TGF-beta1 mRNA expression reached a peak value on
      day 2.5, with a decrease on day 3, and reached the control level on day 7.
      Procollagen types III and IV and fibronectin mRNA reached a peak value on day
      2.5, whereas the expression level of procollagen type I mRNA was maximal on day
      3, and gradually decreased to control levels by day 7. MMP-2 mRNA was
      significantly elevated on day 3, and peaked on day 5, whereas MMP-1 mRNA levels
      did not change throughout the observation period. Immunoreactivity for MMP-2 was
      observed around disrupted acinar cells and interstitial spaces on day 3, and
      maximally on day 7. Immunoreactivity for fibronectin was detected around
      disrupted acinar cells and interstitial spaces. On day 7, it was less than on day
      5 around disrupted acinar cells and interstitial spaces, whereas in the
      regenerated acinar cells, it was undetected. CONCLUSION: Our results show that
      TGF-beta1 mRNA expression peaked earlier than that of ECM mRNA. Furthermore,
      increased level of the MMP-2 transcript was followed by disappearance of
      fibronectin. Our findings suggest that TGF-beta1 plays an important role in ECM
      production in the early phase of acute pancreatitis, and that MMP-2 is involved
      in the subsequent healing process.

PMID- 11590326
TI  - Inhibition of inducible nitric oxide synthase reduces bacterial translocation in
      a rat model of acute pancreatitis.
AB  - INTRODUCTION: Translocation of bacteria from the gut into pancreatic necrosis is
      an important factor in the development of septic complications and mortality in
      acute pancreatitis. S-methylisothiourea (SMT) is an inducible nitric oxide
      synthase inhibitor that has been shown to decrease bacteria] translocation in
      sepsis and thermal injury. AIM: To investigate whether SMT could affect bacterial
      translocation in acute necrotizing pancreatitis. METHODOLOGY: Forty-five Sprague
      Dawley rats were studied. Acute pancreatitis was induced in Group I and Group II
      by injection of taurocholate and trypsin into the common biliopancreatic duct.
      Group III underwent laparotomy with the manipulation (but not cannulation) of the
      pancreas and received saline injection. Group I rats received normal saline as a
      placebo, and Group II rats received SMT after surgery for 2 days. At 48 hours,
      blood was drawn for serum amylase determinations. Bacterial translocation to
      mesenteric lymph nodes and distant sites (pancreas, liver, and peritoneum) were
      examined. A point scoring system of histologic features was used to evaluate the
      severity of pancreatitis. RESULTS: Plasma amylase levels and pancreatic
      histologic score were significantly reduced in Group II rats given SMT compared
      with those in Group I rats given saline (p < 0.01, p < 0.05, respectively). All
      Group I rats had bacterial translocation to mesenteric lymph nodes compared with
      7 of 12 rats in Group II (p < 0.05). There was no difference in bacterial
      translocation to distant organs between the two groups, although rates tended to
      be lower in Group II compared with Group I (p > 0.05). Bacterial counts in the
      pancreas were significantly reduced in Group II rats compared with those in Group
      I rats (p < 0.05). CONCLUSION: Treatment with SMT appears to have ameliorated the
      course of acute pancreatitis; however, mortality was not affected.

PMID- 11590328
TI  - Pancreatic head resection for noninflammatory benign lesions of the head of the
      pancreas.
AB  - INTRODUCTION: Duodenum-preserving pancreatic head resection (DPPHR) has been
      safely performed in patients with chronic pancreatitis. The procedure has rarely
      been used to remove benign or borderline lesions of the head of the pancreas.
      AIMS: To review our experience with 13 patients who underwent DPPHR and to review
      reports in the literature on the same subject. METHODOLOGY: From October 1991 to
      September 2000, 13 patients underwent DPPHR to resect endocrine pancreatic tumors
      (n = 4), beta cell hyperplasia (n = 1), pancreatic pseudocysts (n = 2), serous
      cystadenomas (n = 3), congenital (n = 1) and choledochal (n = 1) cysts, and
      intraductal papillary mucinous tumor (n = 1). The Kocher maneuver was performed
      in seven patients (group 1) and avoided in six (group 2). Type 1, 2, and 3 DPPHR
      were defined depending on the amount of pancreatic tissue left at the inner
      surface of the duodenum. Ten patients underwent evaluation that included an oral
      glucose tolerance test and exocrine pancreatic function test. RESULTS: The
      mortality rate was zero; the complication rate was 69%. Patients in whom the
      Kocher maneuver was not performed (group 2) experienced fewer complications,
      shorter stay on nasogastric tube and abdominal drain(s), and earlier water intake
      and discharge. Type of DPPHR did not influence the postoperative course. One
      patient died 3 months after surgery of unrelated disease. Twelve patients were
      alive and well 2 months to 8 years after surgery. CONCLUSION: DPPHR is a low-risk
      procedure in patients with benign or borderline noninflammatory lesions of the
      head of the pancreas in whom pylorus-preserving pancreaticoduodenectomy is
      otherwise indicated. Whenever possible, the Kocher maneuver should be avoided.

PMID- 11590327
TI  - Immunoneutralization of somatostatin, insulin, and glucagon causes alterations in
      islet cell secretion in the isolated perfused human pancreas.
AB  - INTRODUCTION: In this study, immunoneutralization of endogenous insulin,
      glucagon, and somatostatin with specific antibodies was used in an isolated
      perfused human pancreas (IPHP) model. AIMS: To study intrapancreatic cellular
      interactions and pancreatic hormonal secretion. METHODOLOGY: Randomized,
      sequential 10-minute test intervals of single-pass perfusion with each antibody
      were performed at 3.9 mM or 11.5 mM steady-state glucose concentrations.
      Somatostatin, insulin, and glucagon levels were measured in the effluent during
      basal and immunoneutralization intervals. RESULTS: At 3.9 mM glucose
      concentration, somatostatin antibody (SS-Ab) stimulated insulin and glucagon
      secretion, insulin antibody (IN-Ab) inhibited glucagon secretion, and glucagon
      antibody (GN-Ab) stimulated insulin secretion. At 11.5 mM glucose concentration,
      SS-Ab stimulated insulin secretion, IN-Ab stimulated glucagon and inhibited
      somatostatin secretion, and GN-Ab stimulated insulin secretion. CONCLUSION: The
      variation in hormonal responses to immunoneutralization during stimulated and
      nonstimulated glucose conditions suggests that a dynamic association exists
      between the pancreatic cells.

PMID- 11590329
TI  - Direct administration of interleukin-1 and interferon-gamma to rat pancreas leads
      to the in vivo production of nitric oxide and expression of inducible nitric
      oxide synthase and inducible cyclooxygenase.
AB  - INTRODUCTION: Proinflammatory cytokines may play a pivotal role in the
      pathogenesis of insulin-dependent diabetes mellitus (IDDM). In vitro, the
      formation of nitric oxide (NO) catalyzed by inducible NO synthase (iNOS) has been
      shown to be involved in the cytotoxic effects of cytokines on pancreatic beta
      cells. Cytokines have also been shown to cause the expression of inducible
      cyclooxygenase (COX-2) in isolated islets. AIMS: To describe a novel in vivo
      model that allows investigation of the effects of direct cytokine administration
      to the pancreas. METHODOLOGY AND RESULTS: By using this method, we demonstrate
      that administration of interleukin-1beta and interferon-gamma to rat pancreas
      results in the generation of NO in the treated pancreata as detected by NO
      trapping and electron paramagnetic resonance spectroscopy. Beta cells were
      identified as the source of the formed NO. Reverse transcription and polymerase
      chain reaction analyses showed that administration of cytokines to the pancreas
      leads to the expression of iNOS and COX-2 mRNA in the pancreas tissue as well as
      the islets isolated from such tissues. The compound phenyl N-tert-butylnitrone,
      which protects mice against streptozotocin-induced IDDM, inhibits NO formation
      and downregulates both iNOS and COX-2 mRNA levels.

PMID- 11590330
TI  - Evaluation of pancreatic exocrine function by secretin-enhanced magnetic
      resonance cholangiopancreatography.
AB  - AIM: To assess the feasibility and usefulness of secretin-enhanced magnetic
      resonance cholangiopancreatography (S-MRCP) for evaluation of pancreatic exocrine
      function. METHODOLOGY: S-MRCP was performed in 20 patients with mild (n = 8) or
      severe (n = 12) chronic pancreatitis (according to the grade of exocrine
      pancreatic insufficiency indicated by the Lundh test) and in 10 volunteers
      without pancreatic disease. MRCP images were evaluated before and 10 minutes
      after the intravenous administration of 0.5 IU/kg secretin. The changes in
      pancreatic tissue T2 signal intensity and duodenal filling after the injection of
      secretin were determined by means of S-MRCP. The S-MRCP findings were then
      compared with those of the Lundh test. RESULTS: The pancreatic T2 signal
      intensity showed a significant elevation after secretin administration in the
      volunteers and in the patients with mild or severe chronic pancreatitis. This
      elevation was significantly lower in patients with mild and severe chronic
      pancreatitis than in the volunteers (66.85+/-15.77 and 24.45+/-5.85 vs. 200.0+/
      45.07, respectively). After administration of secretin. the diameter of the
      duodenum was significantly increased in all three groups. This duodenal filling
      was significantly reduced in patients with mild or severe exocrine pancreatic
      insufficiency as compared with the volunteers (4.12+/-1.33 and 1.70+/-0.77 vs.
      15.38+/-1.73, respectively). There was no significant difference in pancreatic T2
      signal intensity changes or in duodenal filling in patients with mild or severe
      exocrine pancreatic insufficiency. There were significant correlations between
      the pancreatic T2 signal intensity changes and the duodenal filling and the
      results of the Lundh test (r = -0.616 and -0.78). CONCLUSION: These results
      demonstrate that the administration of secretin increases the T2 signal intensity
      of the pancreatic tissue and the diameter of the duodenum to different extents in
      normal subjects and in patients with chronic pancreatitis. This suggests that S
      MRCP can provide information of value in the assessment of an exocrine pancreatic
      insufficiency.

PMID- 11590331
TI  - Continuous enteral feeding has an attenuating effect on the exocrine pancreas in
      rats.
AB  - INTRODUCTION: Recent clinical observations suggest that continuous enteral
      feeding (CEF) may exert a beneficial effect in the management of inflammatory
      pancreatic diseases. Its effects on the exocrine pancreas, however, remain only
      partially investigated. AIM: To examine the effects of CEF on the exocrine
      pancreas in rats. METHODOLOGY: Eight male Wistar rats were intrajejunally
      cannulated, and CEF was started on postoperative day 6. In 10 control animals,
      laparotomy was followed by intragastric feeding (GF) with the same nutriment
      (Osmolite, Abbott) from postoperative day 6. The daily discharge was 24 kcal in
      both groups. After 5 days of feeding, the pancreas was removed; its weight and
      its protein, DNA, trypsin, and lipase contents were determined; and the exocrine
      pancreas was also examined for structural changes. RESULTS: The results revealed
      no significant difference in body weight loss between the two groups of animals,
      whereas the pancreas weight/body weight ratio was lower (p < 0.01) in the CEF
      group. The pancreatic protein, DNA, and enzyme contents were decreased (p < 0.01)
      after CEF as compared with the values for the GF group. Histologic examinations
      demonstrated clear decreases in acinar size and in the zymogen content of the
      pancreas in the CEF animals. CONCLUSION: This study clearly indicates that CEF
      reduces the enzyme production of the pancreas.

PMID- 11590332
TI  - [To reform Huriet's law].

PMID- 11590333
TI  - [Skin cancers in organ allograft recipients].

PMID- 11590334
TI  - [Latest reform in 2nd cycle medical studies].

PMID- 11590335
TI  - [Herpes consensus meeting].

PMID- 11590336
TI  - [Viruses involved in allograft recipients'cutaneous carcinomas].
AB  - BACKGROUND: Cutaneous carcinomas are frequent in renal allograft recipients.
      Their treatment can be difficult especially in cases of multiple carcinomas. The
      aim of this study was to determine whether human papillomavirus are more frequent
      in patients group with multiple cutaneous carcinomas and whether other viruses
      such as Epstein-Barr virus, cytomegalovirus, and herpes simplex might be
      associated in this kind of tumour. PATIENTS AND METHODS: Forty-three patients
      were included. Twenty-two had a single carcinoma (group 1) and 21 had multiple
      cutaneous carcinomas (group 2). Histologic analysis and in situ hybridization
      were used to search for Epstein-Barr virus, human papillomavirus, herpes simplex
      virus and cytomegalovirus latency genes. RESULTS: In both groups, epidermoid
      carcinomas were more frequent than basal cell carcinomas and delay between graft
      and first carcinoma was similar (5 years). In situ hybridization was more often
      positive in group 2 (41/50) than in group 1 (13/22). Human papillomavirus DNA was
      detected more frequently in the group with multiple carcinomas (26/50) than in
      the group with a single carcinoma (6/22). Moreover, cytomegalovirus was more
      frequent in group 2. CONCLUSION: This study shows a higher prevalence of human
      papillomavirus DNA in the carcinomas of the multiple carcinoma population.
      Moreover, for the first time, cytomegalovirus DNA was detected in carcinomas of
      renal allograft recipients with a higher frequency in the patients with multiple
      carcinomas.

PMID- 11590337
TI  - [Prevalence of hyperhidrosis in a population treated by beta-blocker].
AB  - INTRODUCTION: Some cases of hyperhidrosis with beta-blocker therapy have been
      reported in the literature. We studied the prevalence of hyperhidrosis in a
      population treated by beta-blockers compared with an untreated control group.
      PATIENTS AND METHODS: Patients attending the cardiologic consultation of the
      Nancy hospital were included. Past medical history and medication were collected.
      Interrogation assessed whether the patient felt hyperhidrosis, and defined a
      hyperhidrosis score. RESULTS: Sixty-five subjects treated by beta-blocker and 100
      controls were included. 36.9 p. 100 of treated patients and 38 p. 100 of controls
      experienced hyperhidrosis (p=0.88). 23.07 and 23 p. 100, respectively, had
      hyperhidrosis defined by a high score of sweating (p=0.99). Retrospectively, 8 of
      24 patients experienced hyperhidrosis after the beginning of beta-blocker
      therapy. DISCUSSION: We observed the same prevalence of hyperhidrosis in the two
      groups. However sweat gland innervation involved both cholinergic and adrenergic
      stimulations. Furthermore, experimental studies showed an increase in sweating on
      efforts with beta-blocker therapy.

PMID- 11590338
TI  - [Skin cancer diagnosis by dermatologists in the region of Champagne-Ardenne: a
      prospective study].
AB  - INTRODUCTION: The exact incidence of skin cancers is not well established in
      France as in other european countries, except for cutaneous melanoma. It is the
      same for the part taken by dermatologists in the screening of skin malignancies.
      We have therefore planned a prospective study in the Champagne-Ardenne region to
      determine the incidence of the various types of skin cancers diagnosed by
      dermatologists. PATIENTS AND METHOD: A prospective study was performed within a 4
      month period at the end of 1998 with the participation of the dermatologists of
      the Champagne-Ardenne and the south of Aisne. The new incident cases of skin
      cancers confirmed histologically were recorded using a questionnaire including
      the type of tumour, demographic data of the patient and type of practice of the
      dermatologist. Parallely, the pathology laboratories of the same region were
      asked about the number of squamous and basal cell carcinomas and melanomas
      diagnosed histologically during the same period of time. RESULTS: The rate of
      participation of dermatologists was 86 p. 100. During the study period, 898 skin
      cancers were diagnosed in 794 patients (408 women and 386 men; mean age 70.1
      years) including 643 basal cell carcinomas, 123 squamous cell carcinomas, 48
      Bowen diseases, 53 melanomas, 7 lymphomas and 24 other tumours. More than 80 p.
      100 of patients were primarily seen in private practice. Ten of 13 pathology
      laboratories of the region replied to the inquiry. From these pathological data,
      585 basal cell carcinomas, 125 squamous cell carcinomas and 44 melanomas were
      recorded during the same period of time. DISCUSSION: This study shows that the
      oncologic clinical practice of dermatologists in our region is considerable.
      Taking into account both participation and exhaustivity rates, one can estimate
      at more than 3,500 the annual number of skin cancers diagnosed by dermatologists
      in our region, with an expected distribution of the various types of cancers. The
      essential role of the dermatologists in screening skin malignancies is confirmed
      by data provided by pathology laboratories. This role is a french characteristic
      and cannot by applied to other industrialized countries.

PMID- 11590339
TI  - [Orf in urban surroundings and religious practices: a study over a 3-year
      period].
AB  - BACKGROUND: Orf is a sheep disease, due to a parapox virus. Men in close contact
      with these animals may be contaminated. This generally occurs during professional
      activities. In our clinic, located in the heart of Brussels, we were surprised by
      the number of orf cases encountered each year, grouped during a short three-week
      period. PATIENTS AND METHODS: We decided to set up a prospective study of three
      years. Forty-four cases (14 to 64 years of age) were observed: 14 in 1998, 18 in
      1999 and 12 in 2000. There were 29 men and 15 women. RESULTS: Only one patient
      had professional contact with sheep; 42 were muslims. Forty-two lesions out of 44
      developed in the same time span, 10 days earlier each year. Complications
      observed were: erythema multiforme (7 cases), lymphangitis (3 cases), axillary
      adenitis (3 cases), eyelid edema (2 cases), generalized maculopapular eruption (2
      cases) and contact dermatitis to the cream applied (1 case). DISCUSSION: This
      peculiar epidemiology can easily be explained: patients are contaminated during a
      religious feast, Aid el Kebir (the Feast of Sacrifice). On this occasion, they
      slaughter sheep, which they manipulate with bare hands. Small trauma often occur
      at that time. We conclude that orf is not only a professional disease but
      particuliar habits may cause epidemic-type contamination.

PMID- 11590340
TI  - [Metastatic melanoma of unknown primary site].
AB  - INTRODUCTION: Melanomas of unknown primary site are rare. To establish their
      diagnosis the metastatic nature of the lesion must be confirmed clinically and
      histologically, the melanoid nature by histology and immunohistochemistry. Any
      primary melanoma must be eliminated by careful examination of the skin and
      mucosa, and the absence of past surgical excision of skin lesions must be
      confirmed. We studied the epidemiological, clinic and prognostic characteristics
      of 19 melanomas of unknown primary site in a series of 646 melanomas. MATERIAL
      AND METHODS: This retrospective study was conducted on a series of 646 melanomas
      recruited over a period of 14 years. The epidemiological (age, gender, phototype
      and family history of melanoma), clinical and prognostic parameters (relapse and
      global survival rate) were analyzed in 19 patients. Clinical and epidemiological
      data were compared with the 646 melanomas of the series. The prognostic
      parameters were compared with the melanomas of the series at the same stage.
      RESULTS: The melanomas with unknown primary site represented 2.94 p. 100 of our
      series and concerned 10 men and 9 women with a median age of 60 years. Eight
      patients presented stage III melanomas, according to MD Anderson's classification
      and 11 stage IV. Relapse after surgery was observed in 63 p. 100 of patients and
      9 deceased during the observation period. In stage III patients the probability
      of survival after 2 years was of 51 p. 100 and for stage IV 34 p. 100.
      DISCUSSION: In our series the frequency of melanomas of unknown primary site is
      comparable to that observed in other studies. Compared to melanomas of known
      primary site, there was a preponderance in men and in slightly older patients.
      There was a majority of single glandular localizations and no particular site was
      preponderant. Survival of Stage III patients was comparable to that of melanomas
      of know primary site. However, for stage IV patients it appeared better, as has
      been noted in other series. Treatment of metastatic melanomas of unknown primary
      site should therefore be the same as that of classical forms. Whenever possible,
      surgery remains the first indication. Search for the primary site must be
      orientated by clinical examination including complete examination of the skin and
      mucosa (ENT, ophthalmologic and genito-urinary), eventually associated with
      paraclinical investigations, depending on the symptoms.

PMID- 11590342
TI  - [Metronidazole].
AB  - Metronidazole was first introduced for the treatment of trichomoniasis. Now, its
      therapeutics use has subsequently been expanded to include protozoal and
      anaerobic infections. Oral administration is recommended: rosacea, perioral
      dermatitis, Helicobacter pylori, Trichomonas vaginalis and Giardia lamblia
      infections and bacterial vaginosis. Metronidazole given orally is absorbed almost
      completely. Metronidazole has limited plasma protein binding but can reach very
      favourable tissue distribution, including central nervous system and placenta.
      This drug is extensively metabolised by the liver to form 5 oxydative
      metabolites. The majority of this drug and metabolites are excreted in urine and
      feces. The half-life is 6 to 10 hours. The recommended dose is 500 mg three time
      per day and an adaptation is necessary in renal insufficiency. Metronidazole is
      well tolerated when administered in dosages of less than 2 g per day. Some
      adverse reactions appear to be related to the high dosages and treatment
      duration. Drug interactions with alcohol, warfarin and phenytoin have been
      reported. Mutagenesis and cancerogenesis is only described in mouse. Resistance,
      both clinical and microbiological, has been described only rarely.

PMID- 11590341
TI  - [Cutaneous filariasis Loa Loa: 26 moroccan cases of importation].
AB  - INTRODUCTION: Loa Loa filariasis or loiasis is a subcutaneous and bloody
      vectorial parasitosis. It is endemic in forest and swamp areas of west and
      central Africa. PATIENTS AND METHODS: We reviewed 26 moroccan cases of
      importation. All patients had visited Equatorial Guinea. Transient and migratory
      edema with pruritus were described in all cases and seen in 5 cases. A history of
      eyeworm was reported in 13 patients and subcutaneous migration of adult Loa Loa
      in 19 patients. Other features including fever and asthenia were reported in 11
      patients. Microfilaremia was positive in 8 patients and eosinophilia was present
      in 22 patients. Fifteen patients were treated with diethylcarbamazine alone and 9
      patients with ivermectin and diethylcarbamazine. Two patients were treated with
      ivermectin alone. Relapses were noted in 8 cases. No visceral complications were
      noted excepting one case of terminal hematury. DISCUSSION: Loiasis is a filarial
      infection of man that occurs exclusively in central and West Africa. The most
      common symptoms being pruritus with temporary, localised edema, subcutaneous and
      subconjonctival eye passage of the adult worm, fever and fatigue. The biologic
      diagnosis of loaisis is made on peripheral microfilariae, filarial serology and
      eosinophil count. Travel and visits endemic areas were at the origin of the
      emergence of this pathology in Morocco. Filarial Loa Loa infection should be
      treated with diethylcarbamazine and/or ivermectin.

PMID- 11590343
TI  - [Vascular purpura in a patient with severe sarcoptic acariasis].
AB  - INTRODUCTION: The common cutaneous manifestations of human sarcoptic acariasis
      are erythematous and pruriginous papules. Vascular purpura in patients with
      scabies has rarely been reported. We report a case of vascular purpura in the
      presence of a transient elevation of anticardiolipin antibodies. CASE REPORT: A
      79 year-old woman was treated with prednisone and chlorambucil for a lymphoma.
      She was referred to our institution for diffuse sarcoptic acariasis. Clinical
      examination showed a petechial purpura on her legs. Histology of two biopsies of
      purpuric papules showed non inflammatory thrombosis of the upper dermis vessels.
      Investigations revealed a transient elevation of anticardiolipin antibodies,
      moderate hyperhomocysteinaemia and blood eosinophilia. Treatment consisted in
      ivermectin and repeated applications of benzyl benzoate lotion. The purpura
      healed within one month, without specific treatment. DISCUSSION: Histological
      findings of sarcoptic acariasis with vascular purpura correspond to
      leukocytoclasic vasculitis. Focal glomerulonephritis has been reported. In our
      case, histopathology showed a non inflammatory thrombosis of the dermal vessels.
      We hypothesize that the anticardiolipin antibodies, hyperhomocysteinaemia and
      blood eosinophilia may have been the cause of vascular thrombosis.

PMID- 11590344
TI  - [Melorheostosis associated with arteriovenous malformation of the ear].
AB  - BACKGROUND: Melorheostosis is a rare bone dystrophy that may be associated with
      various vascular malformations. We report a case of arteriovenous fistulae of the
      ear associated with melorheostosis limited to the same side of the body. CASE
      REPORT: A 13 year-old boy presented a congenital port-wine nevus of the right
      side of the head complicated by an arteriovenous fistulae and angiomatous nodules
      of the ear. He was treated by laser, surgery of the nodules, arterial
      embolisations and sclerotherapy. In 1999, he had a benign trauma of the right
      hand. The X-ray showed hyperostosis resembling wax flowing down a candle reaching
      the carpus and some of the metacarpals and the phalanges of the right hand,
      typical of melorheostosis. The complete radiographic check-up showed the same
      characteristic appearance on the right side of the skull and the long bones of
      the right upper limb. Except a deformation of the right fingers, there were no
      others symptoms. DISCUSSION: Melorheostosis is a rare, sporadic and benign bone
      dysplasia that may be localized to a single limb or disseminated. The diagnosis
      is usually made in late childhood. Pain, stiffness, deformation of a limb are the
      main clinical manifestations. The skin may be erythematous and sclerotic. The
      radiographic appearance is characteristic with hyperostosis on one side of the
      bone resembling wax flowing down a candle. A vascular abnormality is present in
      17 p. 100 of cases (hemangiomas, aneurysms, renal artery stenosis.). In these
      cases, melorheostosis is usually limited to the same side of the vascular lesion.
      We report the first case of arteriovenous fistulae of the ear associated with
      melorheostosis, on the same side of the body. The physiopathology of
      melorheostosis is still unknown but the association with a homolateral vascular
      abnormality suggests a localized defect in embryogenesis of the vascular and
      skeletal systems.

PMID- 11590345
TI  - [Multiple skin and mouth squamous cell carcinomas related to long-term treatment
      with hydroxyurea].
AB  - INTRODUCTION: Cutaneous side-effects of hydroxyurea treatment are frequently
      observed. Squamous cell carcinomas are the most severe among them. We report a
      patient with skin and mouth carcinomas after hydroxyurea treatment. To the best
      of our knowledge, this is the first case reported. OBSERVATION: A 83-year-old
      woman had been treated with hydroxyurea from 1985 to 1998 for polycythemia vera.
      She was referred to our institution in 1998 for painful erosions of both hands.
      Clinical examination revealed a squamous cell carcinoma leading to amputation of
      a finger. Hydroxyurea was stopped at this time, and the patient underwent
      treatment with pipobroman. From May 1998 to March 2000, the patient developed
      numerous skin keratoses and four squamous cell carcinomas on both hands. In
      September 2000 and October 2000, two additional skin carcinomas and two mouth
      carcinomas were diagnosed. DISCUSSION: Cutaneous carcinomas are severe side
      effects of hydroxyurea therapy. They usually occur after several years of
      treatment and their outcome may be lethal. The chronology and clinical signs are
      in favour of implicating hydroxyurea in the development of skin and mouth
      carcinomas. Despite a bibliographic research using Medline and Embase data bases,
      we could not find another case-report with simultaneous occurrence of skin and
      mouth carcinomas after hydroxyurea therapy. This observation emphasizes the need
      of a long term follow-up in patients receiving hydroxyurea.

PMID- 11590346
TI  - [Erythrocyanosis].

PMID- 11590347
TI  - [Spontaneous occurrence of hypertrophic scars].

PMID- 11590348
TI  - [How many patients?].

PMID- 11590349
TI  - [Acute ulcer of the vulva].

PMID- 11590350
TI  - [Pityriasis rubra pilaris].

PMID- 11590351
TI  - [Contact hypersensitivity and cross-reactions to topical corticosteroids].

PMID- 11590352
TI  - [News in pseudoxanthoma elasticum].

PMID- 11590353
TI  - [The molecular genetics of pseudoxanthoma elasticum].

PMID- 11590354
TI  - [Radiation induced skin reaction].

PMID- 11590355
TI  - [Treatment of cutaneous lupus erythematosus].

PMID- 11590357
TI  - [Law of December 20, 1988: revision].

PMID- 11590356
TI  - [Winer's calcinosis].

PMID- 11590359
TI  - [Isotretinoin and smoking].

PMID- 11590360
TI  - [Ernest Gaucher (1854-1919)].

PMID- 11590361
TI  - [Reform of the 2nd part of the 2nd cycle of medical teaching in France].

PMID- 11590362
TI  - [Is DHEA useful?].

PMID- 11590363
TI  - Evidence for indirect control of phospholipase C (PLC-beta) by retinoids in
      Drosophila phototransduction.
AB  - PURPOSE: To determine how retinoids regulate the phospholipase C (PLC) gene in
      the Drosophila visual system. METHODS: Western blotting, activity analyses and
      immunocytochemistry were applied to Drosophila reared on various diets. RESULTS:
      Western blots and activity analyses showed that retinoid deprivation decreases
      PLC, the product of the norpA gene, by approximately 1/3 to 1/2 in Drosophila.
      Immunocytochemistry using standard and confocal fluorescence microscopy confirmed
      the expectation that PLC is localized to the photoreceptive rhabdomeres.
      Rhabdomeres of flies that were retinoid deprived, or reared on other diets devoid
      of chromophore precursors, fluoresced brightly. These observations are consistent
      with earlier morphometric analyses showing that retinoid deprivation decreases
      the size of rhabdomeres. In a separate control, rhabdomeric PLC was shown to be
      virtually eliminated by retinoid deprivation in transgenic Drosophila where the
      norpA coding sequence was driven by the opsin promoter. CONCLUSIONS: PLC is
      decreased by retinoid deprivation. Retinoid control of PLC is indirect, as
      expected, since the norpA promoter is so different from the promoter for
      rhodopsin's gene. PLC is not eliminated by deprivation but decreases in
      proportion to the associated decrease in rhabdomere size which, in turn, is
      caused by the opsin decrease. By contrast, opsin is controlled by retinoids both
      translationally by chromophore availability and transcriptionally. The fact that
      PLC is eliminated by retinoid deprivation when opsin's promoter drives the PLC
      gene is important evidence substantiating retinoid control via opsin's promoter.

PMID- 11590364
TI  - Cloning and characterization of three salamander retinal G-protein beta subunits.
AB  - PURPOSE: Recent evidence has shown that the beta-gamma dimers (beta gamma) of
      activated heterotrimeric G-proteins are important in many cellular signaling
      pathways. Since two distinct transducin alpha subunits have been cloned from the
      salamander retina, we aimed to identify and characterize the G-protein beta
      (Gbeta) subunits that are involved in visual signal transduction in the
      salamander. METHODS: A salamander retina cDNA library was screened using
      degenerate oligonucleotide primers designed from a compilation of known Gbeta
      sequences. Tissue specific expression was determined by reverse transcriptase PCR
      (RT-PCR). RESULTS: The library screening resulted in the cloning of three full
      length sequences, two of which encode proteins of 340 residues and the third
      being an iniation variant of 353 and 395 residues. No identical matches were
      found in GenBank but each shows highest homology to G-beta-1 (beta1), G-beta-3
      (beta3), and G-beta-5 (beta5 and beta5L) subunits of other species, respectively.
      The beta1 and beta3 subunits are 84.7% identical to each other but both show only
      52% identity to beta5 at the protein level. RT-PCR analysis showed that all the
      subunits are expressed in multiple tissues, including the retina. However, the
      beta5L splice variant was found only in the retina. CONCLUSIONS: Three distinct
      Gbeta subunit transcripts are expressed in the salamander retina. These subunits
      have proven to be important in the visual system of mammalian models.

PMID- 11590365
TI  - Heat-induced quaternary transitions in hetero- and homo-polymers of alpha
      crystallin.
AB  - PURPOSE: To compare the effects of heat incubation on the structure and function
      of native alpha-crystallin, urea denatured/renatured alpha-crystallin, and alphaA
      and alphaB-crystallin homo-polymers purified from bovine lenses. METHODS: Each of
      the alpha-crystallin samples were incubated for 1 h at temperatures ranging from
      35 degrees C to 70 degrees C. After heat incubation structural perturbations in
      each of the samples were studied using non-denaturing gel electrophoresis,
      transmission electron microscopy (TEM) and far-UV circular dichroism. The
      chaperone-like activity of each of the heat-treated samples was measured using
      the DTT induced insulin aggregation assay. RESULTS: The native alpha-crystallin
      samples showed secondary structure perturbations, an increase in aggregate size
      and asymmetry, and an increase in chaperone-like activity after heat incubation
      above 50 degrees C. The other three sample types showed secondary structure
      perturbations beginning at lower incubation temperatures, and a progressive
      decrease in chaperone-like activity with exposure to increasing temperatures. TEM
      showed all samples formed large asymmetric high molecular weight aggregates after
      incubation at 65 degrees C. CONCLUSIONS: The urea denaturation/renaturation of
      alpha-crystallin has been shown to result in the loss of a small amount of alpha
      helix, but to have no effect on chaperone-like activity under standard test
      conditions. The present results indicate this lost alpha-helix may be responsible
      for the differential effects of heat incubation on the different forms of alpha
      crystallin.

PMID- 11590366
TI  - Identification, genomic structure, and screening of the vacuolar proton-ATPase
      membrane sector-associated protein M8-9 gene within the COD1 critical region
      (Xp11.4).
AB  - PURPOSE: Our goal is to identify the gene responsible for X-linked cone-rod
      dystrophy (COD1) that has been localized to a limited region of Xp11.4. METHODS:
      A complete physical contig of the COD1 region was partially sequenced and
      subjected to BLAST searches to identify homologies with GenBank ESTs. ESTs were
      analyzed for overlapping or related cDNA sequences and retinal expression by PCR
      screening of multiple human retina cDNA libraries. RACE was performed to complete
      the missing 5' end of the transcripts. Transcripts were compared with genomic
      sequences to specify intron-exon boundaries. Genomic DNAs from COD1-affected
      males from 3 families were screened for mutations using direct PCR sequencing of
      the exons. RESULTS: The vacuolar proton-ATPase membrane sector-associated protein
      M8-9 (APT6M8-9) gene was identified within our critical region. We confirmed its
      retinal expression and its genomic location in our physical contig. Eight exons
      (with flanking intronic sequences) were characterized from partial cDNA sequence
      and genomic sequence data. An additional 5' end exon was identified using RACE.
      No mutations were found in the COD1-affected males. CONCLUSIONS: The combination
      of disease mapping and information from the Human Genome project has enabled us
      to identify candidate genes within the COD1 region, including APT6M8-9 gene. We
      found no evidence that this gene is responsible for COD1 in our families, but it
      may be an important candidate for other diseases that have been mapped to this
      region of the X chromosome.

PMID- 11590368
TI  - Drug metabolism, danger signals, and drug-induced hypersensitivity.
AB  - One of the most difficult challenges for the practicing allergist/immunologist
      today is that of evaluating and managing patients who present with histories of
      drug-induced reactions. Adverse drug reactions are heterogeneous, and a single
      drug can often cause a multitude of reactions. Because the mechanisms responsible
      for many of these reactions are not known, they can be, and often are, difficult
      to classify. Moreover, for those that have features consistent with immune
      mediated mechanisms, our diagnostic tools remain limited, because little is known
      about the relevant immunogenic determinants of most drugs. Despite these
      challenges, management approaches must be devised for patients who present with
      histories of drug-induced disease. Simply telling such a patient to avoid all
      drugs that have been associated with previous adverse events leaves both the
      patient and the referring physician frustrated. The initial part of this review
      focuses on exciting current research that is furthering our understanding of the
      mechanisms responsible for drug-induced reactions. Because it will take time to
      translate this new information into clinical practice, the latter part of the
      review focuses on ways to evaluate and manage patients who present with drug
      induced reactions using the tools and the knowledge that are currently available.

PMID- 11590369
TI  - IL-11: insights in asthma from overexpression transgenic modeling.
AB  - The evolution of our understanding of IL-11 mirrors, in many ways, the problems
      that are faced by investigators in the post-genome era and the types of
      techniques that might need to be used to deal with these issues. IL-11 was
      discovered as a soluble factor in fibroblast supernatants that stimulated the
      proliferation of "IL-6-dependent" plasmacytoma cells. It was subsequently
      demonstrated to be an important stimulator of platelet reconstitution and a
      pleiotropic regulator of nonrespiratory tissues. In the lung, IL-11 is produced
      by a variety of structural cells and eosinophils in response to a variety of
      stimuli, including TGF-beta, major basic proteins, and viruses. IL-11 is also
      detected in exaggerated quantities at sites of virus infection. Its potential
      effector functions at these sites were defined with constitutive and inducible
      overexpression transgenic modeling systems which demonstrated that IL-11 causes
      nodular mononuclear infiltrates, airway remodeling with subepithelial fibrosis,
      airways obstruction, and airways hyperresponsiveness and can block alveolar
      development when expressed during development. In accord with these murine
      findings, IL-11 is selectively expressed in eosinophils and epithelial cells in
      patients with moderate and severe asthma where expression correlates directly
      with disease severity and inversely with FEV(1). Studies using transgenic mice
      also demonstrated that IL-11 inhibits antigen-induced tissue inflammation. Thus
      IL-11 might be an important regulator of inflammatory and remodeling responses in
      the asthmatic airway.

PMID- 11590370
TI  - "ARIA": global guidelines and new forms of allergen immunotherapy.

PMID- 11590371
TI  - What should we tell allergic families about pets?

PMID- 11590372
TI  - The trials and tribulations of IL-5, eosinophils, and allergic asthma.
AB  - Eosinophils have been suggested to be part of the pathologic process that
      characterizes asthma, and their recruitment into the upper or lower airways
      appears to be essential for the clinical manifestations of allergen inhalation.
      IL-5 is a cytokine necessary for the development, differentiation, recruitment,
      activation, and survival of eosinophils. Allergen inhalation increases the
      production of IL-5 in the airways as measured in bronchoalveolar lavage cells and
      induced sputum. The relationship between IL-5 and the development of airway
      eosinophilia has been firmly established in IL-5 transgenic mice, with allergen
      challenge models in IL-5-deficient mice, and in mice treated with blocking anti
      IL-5 antibodies. In addition, an accumulation of evidence suggests that treating
      mice with anti-IL-5 blocking antibodies prevents allergen-induced airway
      hyperresponsiveness. A recently reported study examined the effects of treatment
      with a humanized anti-IL-5 mAb (SB-240563) on allergen-induced airway responses
      and inflammation in atopic subjects. The authors of the study concluded that
      their results call into question the role of eosinophils in mediating the
      allergen-induced late asthmatic response and airway hyperresponsiveness; however,
      because of methodologic limitations, the study cannot be used either to support
      or to refute the concept of an important role for eosinophils in causing allergen
      induced changes in airway function.

PMID- 11590373
TI  - Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not
      of atopy.
AB  - BACKGROUND: Influence of household pets in the development of childhood asthma or
      atopy has been controversial. OBJECTIVE: The purpose of this study was to
      investigate whether pet exposure in early life decreases the subsequent risk of
      frequent wheezing and/or allergic sensitization. METHODS: This was a prospective
      observational birth cohort study. The setting was a large health maintenance
      organization in Tucson, Ariz; the subjects were a population sample of 1246
      newborns enrolled at birth and followed prospectively to age 13 years. The main
      outcome measures were as follows: time to first report of frequent wheezing (>3
      episodes in the past year), skin prick test reactivity at 6 years and 11 years of
      age, and total serum IgE at 9 months, 6 years, and 11 years of age. RESULTS:
      Children living in households with > or =1 indoor dogs at birth were less likely
      to develop frequent wheeze than those not having indoor dogs (P =.004). This
      inverse association was confined to children without parental asthma (hazard
      ratio = 0.47; P <.001 [Cox regression]) and was not evident for children with
      parental asthma (hazard ratio = 0.96; P =.87). Adjustment by potential
      confounders did not change the results. Indoor cat exposure was not significantly
      associated with the risk of frequent wheezing. Neither cat exposure in early life
      nor dog exposure in early life was associated with skin prick test reactivity or
      total serum IgE at any age. CONCLUSION: Dog exposure in early life might prevent
      the development of asthma-like symptoms, at least in low-risk children with no
      family history of asthma. Nevertheless, early pet exposure does not seem to
      significantly influence the development of allergic sensitization.

PMID- 11590374
TI  - Allergy development and the intestinal microflora during the first year of life.
AB  - BACKGROUND: The intestinal microflora is a likely source for the induction of
      immune deviation in infancy. OBJECTIVE: The purpose of this study was to
      prospectively relate the intestinal microflora to allergy development in 2
      countries differing with respect to the prevalence of atopic diseases. METHODS:
      Newborn infants were followed prospectively through the first 2 years of life in
      Estonia (n = 24) and Sweden (n = 20). By that age, 9 Estonian and 9 Swedish
      infants had developed atopic dermatitis and/or positive skin prick test results.
      Stool samples were obtained at 5 to 6 days and at 1, 3, 6, and 12 months, and 13
      groups of aerobic and anaerobic microorganisms were cultivated through use of
      standard methods. RESULTS: In comparison with healthy infants, babies who
      developed allergy were less often colonized with enterococci during the first
      month of life (72% vs 96%; P <.05) and with bifidobacteria during the first year
      of life (17% to 39% vs 42% to 69%; P <.05). Furthermore, allergic infants had
      higher counts of clostridia at 3 months (median value, 10.3 vs 7.2 log(10); P
      <.05). The prevalence of colonization with Staphylococcus aureus was also higher
      at 6 months (61% vs 23%; P <.05), whereas the counts of Bacteroides were lower at
      12 months (9.9 vs 10.6 log(10); P <.05). CONCLUSION: Differences in the
      composition of the gut flora between infants who will and infants who will not
      develop allergy are demonstrable before the development of any clinical
      manifestations of atopy. Because the observations were made in 2 countries with
      different standards of living, we believe that our findings could indicate a role
      for the intestinal microflora in the development of and protection from allergy.

PMID- 11590375
TI  - Comparison of cellular composition of induced sputum analyzed with Wright
      staining and immunocytochemistry.
AB  - We sought to compare cell counts based on cellular morphology and obtained after
      Wright staining with cell counts obtained after immunocytochemistry in induced
      sputum. Counts of eosinophils, neutrophils, macrophages, lymphocytes, and
      epithelial cells identified after Wright staining were compared with the counts
      obtained after immunocytochemistry through use of mAbs in 25 samples. Agreement
      between Wright staining and immunocytochemistry was poor for lymphocytes and
      epithelial cells. Rather than Wright staining, immunocytochemistry should be used
      to accurately identify lymphocytes and epithelial cells.

PMID- 11590376
TI  - Distinct pattern of immune cell population in the lung of human fetuses with
      cystic fibrosis.
AB  - BACKGROUND: Airway inflammation and infection are early events in cystic fibrosis
      (CF) pathogenesis. The existence of an imbalance in the immune cell population of
      the CF fetal airway before infection remains completely unknown. OBJECTIVE: The
      aim of this study was to determine whether early signs of inflammation are
      observed in CF airways during human fetal development. METHODS: Tracheas and
      lungs were collected from 21 CF and 16 non-CF fetuses. In tissue sections, the
      numbers of neutrophils, mast cells, macrophages, and B and T lymphocytes were
      quantitatively analyzed by means of image cytometry. The presence of IL-4, IL-6,
      IL-8, IL-10, RANTES, IFN-gamma, TNF-alpha, and NF kappa B and its inhibitor I
      kappa B-alpha was qualitatively evaluated by immunofluorescent staining. RESULTS:
      During fetal airway development, epithelial and glandular differentiation, as
      well as the distribution of inflammatory markers, was similar in CF and non-CF
      tissues. Significant differences between CF and non-CF fetal airways were
      observed only in the numbers of mast cells and macrophages. In the CF trachea,
      the mast cell number increased slowly but continuously, whereas in the non-CF
      trachea this number rapidly reached a plateau. In the CF lung, the macrophage
      number increased with time, whereas in the non-CF lung it decreased. CONCLUSION:
      Although no intrinsic inflammation was demonstrated, we observed a distinct
      appearance of mast cells and macrophages in CF airways in comparison with non-CF
      airways during fetal development. These 2 cell populations were greater in CF
      airways at a late stage of fetal development, suggesting their possible
      involvement in the early onset of inflammation in CF infants.

PMID- 11590377
TI  - The phosphodiesterase 4 inhibitor roflumilast is effective in the treatment of
      allergic rhinitis.
AB  - BACKGROUND: The beneficial effects of phosphodiesterase 4 (PDE4) inhibitors in
      allergic asthma have been shown in previous preclinical and clinical studies.
      Because allergic rhinitis and asthma share several epidemiologic and
      pathophysiologic factors, PDE4 inhibitors might also be effective in allergic
      rhinitis. OBJECTIVE: The main objective of this study was to investigate the
      efficacy of oral roflumilast (500 microg/day) in allergic rhinitis. METHODS: In a
      randomized, placebo-controlled, double-blinded, crossover study, 25 subjects (16
      male, 9 female; median age, 28 years) with histories of allergic rhinitis but
      asymptomatic at screening received roflumilast (500 microg once daily) and
      placebo for 9 days each with a washout period of at least 14 days in between
      treatment periods. In each of the treatment periods, controlled intranasal
      allergen provocation with pollen extracts was performed daily beginning the third
      day of treatment, each time approximately 2 hours after study drug
      administration. Five and 30 minutes after each allergen provocation, rhinal
      airflow was measured by means of anterior rhinomanometry and the subjective
      symptoms obstruction, itching, and rhinorrhea were assessed by means of a
      standardized visual analog scale. RESULTS: Rhinal airflow improved almost
      consistently during the 9 days of roflumilast treatment, and it was significantly
      higher at study day 9 on roflumilast in comparison with placebo, a result also
      found for itching and rhinorrhea. With respect to the subjective obstruction
      score, a significant difference in comparison with placebo could be demonstrated
      within 4 days. CONCLUSION: This study shows that a PDE4 inhibitor, roflumilast,
      effectively controls symptoms of allergic rhinitis. Thus PDE4 inhibitors might be
      a future treatment option not only in allergic asthma but also in allergic
      rhinitis or the combination of the 2 diseases.

PMID- 11590378
TI  - Decreased prevalence of sensitization to cats with high exposure to cat allergen.
AB  - We investigated the relationship between current exposure to cat allergen and
      sensitization to cats. A questionnaire was administered and skin prick testing
      and home visits for collection of dust samples (Fel d 1; ELISA) were performed in
      2502 adults (mean age, 31.8 years; age range, 18-58 years; 1251 women). The
      results for Fel d 1 in relation to sensitization to cats were analyzed for 10
      deciles of cat allergen exposure (cut points [microg/g]: 0.05, 0.34, 0.48, 0.72,
      1.13, 1.92, 7.2, 44, 151). The prevalence of sensitization to cat was
      significantly decreased in the lowest and the highest exposure groups. In the
      multivariate regression analysis (age, sex, socioeconomic status, and current
      smoking being adjusted for), the risk of sensitization to cats was significantly
      increased with medium exposure to Fel d 1 (3rd centile, OR 2.3, 95% CI 1.2-4.4, P
      =.01; 4th centile, OR 2.1, 95% CI 1.1-4.0, P =.03; 5th centile, OR 2.2, 95% CI
      1.2-4.3, P =.04, 6th centile, OR 2.5, 95% CI 1.3-4.9, P =.005). These results
      indicate that the prevalence of sensitization to cat is decreased in the lowest
      and highest cat allergen exposure groups.

PMID- 11590379
TI  - Response of preschool children with asthma symptoms to fluticasone propionate.
AB  - BACKGROUND: Many uncertainties remain in the diagnosis and treatment of preschool
      children with asthma symptoms. OBJECTIVE: We sought to determine the subgroups of
      preschool children (aged 12-47 months) with recurrent asthma symptoms most likely
      to respond to inhaled fluticasone propionate (200 microg/d). METHODS: Subgroups
      of pooled data from 2 similar 12-week multicenter studies were analyzed. RESULTS:
      Children with frequent symptoms (symptoms on > or =3 days per week and a total of
      > or =75% days with symptoms during the 4-week run-in period; n = 169) showed a
      significantly greater increase in days without symptoms after fluticasone
      propionate treatment (0% to 45%) compared with after placebo treatment (0% to
      25%, P =.005). Children with a family history of asthma (n = 213) also had a
      significantly greater increase in days without symptoms after fluticasone
      propionate (11% to 54%) compared with after placebo (7% to 35%, P =.002) and a
      significantly higher proportion of exacerbation-free patients (61% to 76%, P
      =.02). Children with less frequent symptoms, no family history of asthma, or both
      showed no significant treatment effect. There seemed to be no association between
      response to fluticasone propionate and history of rhinitis or eczema or the
      number of previous exacerbations. CONCLUSIONS: Children with frequent symptoms, a
      family history of asthma, or both showed the greatest response to fluticasone
      propionate treatment. These findings may help to predict treatment outcome and
      guide the management of preschool children with recurrent asthma symptoms.

PMID- 11590380
TI  - Fas deficiency delays the resolution of airway hyperresponsiveness after allergen
      sensitization and challenge.
AB  - BACKGROUND: In asthma, persistent inflammation might be the result of (1) an
      impaired ability to clear inflammatory cells from the airways and/or (2) impaired
      apoptotic responses. OBJECTIVE: In a mouse model, we investigated the regulatory
      role of Fas (CD95)-induced apoptosis in the development and resolution of airway
      inflammation and airway hyperresponsiveness (AHR). METHODS: Mice that were either
      Fas-sufficient (wild-type; WT) or Fas-deficient (lpr ) were sensitized by
      intraperitoneal injections of ovalbumin (OVA) and challenged once intranasally
      with OVA (IP-IN mice). Control (IN) mice were challenged only. RESULTS: IP-IN WT
      mice developed AHR at 48 hours; changes in airway resistance resolved by 96
      hours. Airway responsiveness at 48 hours in IP-IN lpr mice was similar to that in
      IP-IN WT mice. However, in contrast to WT mice, IP-IN lpr mice sustained
      significant AHR at 96 hours in comparison with IN lpr mice; the AHR resolved by 6
      days. Bronchoalveolar lavage fluid cell composition was similar in all of the
      different groups at 48 hours and 96 hours. Both IP-IN WT mice and lpr mice
      exhibited similar tissue eosinophilia, whereas IP-IN lpr mice had significantly
      lower numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive cells in
      comparison with IP-IN WT mice at 48 hours. Anti-IL-5 antibody given to IP-IN lpr
      mice 48 hours and 72 hours after the challenge significantly decreased AHR and
      eosinophilic inflammation and increased TUNEL-positive cell numbers at 96 hours.
      CONCLUSION: These results suggest that Fas expression can regulate the onset and
      resolution of AHR through an increase in eosinophil apoptosis.

PMID- 11590381
TI  - Extended allergen exposure in asthmatic monkeys induces neuroplasticity in
      nucleus tractus solitarius.
AB  - BACKGROUND: Extended exposure to allergen exacerbates asthma symptoms, in part
      via complex interactions between inflammatory cells and mediators. One
      consequence of these interactions is the triggering of local and central nervous
      system (CNS) neuronal activity that might further exacerbate the asthma-like
      symptoms by causing bronchoconstriction, mucous secretion, increased
      microvascular leak, and cough. One CNS region that might be particularly
      important is the caudomedial nucleus tractus solitarius (NTS). NTS neurons not
      only integrate primary afferent inputs from lung sensory nerve fibers but also
      have direct exposure to inhaled allergens and allergen-induced blood-borne
      inflammatory mediators via a deficient blood-brain barrier. Given the capacity of
      CNS neurons to undergo plasticity, allergen-induced changes in NTS neuronal
      properties could contribute to the exaggerated respiratory responses to extended
      allergen exposure. OBJECTIVE: In a recently developed rhesus monkey model of
      allergic asthma, we tested the hypothesis that extended exposure to allergen
      increases the intrinsic excitability of NTS neurons. METHODS: Three adult monkeys
      were sensitized and then repeatedly exposed to aerosols of house dust mite
      allergen; 4 monkeys served as controls. Whole-cell current-clamp recordings were
      made to measure 3 indices of excitability: resting membrane potential, input
      resistance, and number of action potentials evoked by current injections.
      RESULTS: Extended allergen exposure depolarized the resting membrane potential by
      14% and increased the number of action potentials evoked by current injections (5
      fold). CONCLUSION: The finding that NTS neurons in a primate model of allergic
      asthma undergo intrinsic increases in excitability suggests that CNS mechanisms
      might contribute to the exaggerated symptoms in asthmatic individuals exposed to
      allergen.

PMID- 11590382
TI  - Chemokine receptor expression profile of eosinophils at inflamed tissue sites:
      Decreased CCR3 and increased CXCR4 expression by lung eosinophils.
AB  - BACKGROUND: To date, most studies dealing with eosinophil chemokine receptors
      have used eosinophils isolated from peripheral blood. During the movement of
      eosinophils from the peripheral blood to inflamed tissue sites,
      microenvironmental signals might alter their expression of chemokine receptors.
      However, little is known about the profile of expression of chemokine receptors
      by eosinophils at inflamed tissue sites in human beings. OBJECTIVE: The purpose
      of this study was to determine whether eosinophils that have migrated into
      inflamed tissues exhibit a profile of chemokine receptor expression that is
      qualitatively and/or quantitatively different from that of eosinophils in
      peripheral locations. METHODS: We studied simultaneously the expression and
      function of chemokine receptors in eosinophils in both bronchoalveolar lavage
      fluid (BALF) and peripheral blood specimens of 7 patients with eosinophilic lung
      diseases. RESULTS: De novo expression of CCR2, CCR4, and CCR5 was not detected at
      either the protein or the mRNA level. However, surface expression of CCR3 was
      decreased and CXCR4 was conversely increased with statistical significance in
      BALF eosinophils. Moreover, the changes in CCR3 and CXCR4 expression were
      reflected in the altered migratory response to their ligands. On the other hand,
      the levels of CXCR1, CXCR2, CXCR3, and CCR1 were virtually unchanged in BALF
      eosinophils, and these receptors did not have functional significance.
      CONCLUSION: Eosinophils at inflamed tissue sites exhibited an expression profile
      qualitatively similar to that in peripheral locations, except for decreased CCR3
      and increased CXCR4 expression. Our results suggest that CCR3 is primarily and
      CXCR4 is cooperatively involved in eosinophil accumulation at inflamed tissue
      sites.

PMID- 11590383
TI  - The enhanced effect of a hexameric deoxyriboguanosine run conjugation to CpG
      oligodeoxynucleotides on protection against allergic asthma.
AB  - BACKGROUND: Oligodeoxynucleotides containing a CpG motif (CpG ODNs), as potent
      inducers of T(H)1 immunity, are considered promising candidates for immune
      modulation in asthma. We have previously demonstrated that conjugation of a
      hexameric deoxyriboguanosine run to the 3' terminus (3' dG(6)-run) of
      phosphodiester (PE) CpG ODNs enhanced their immuno-stimulatory activities in
      vitro. OBJECTIVE: This study aimed to evaluate the effect of a 3' dG(6)-run
      conjugation to PE or phosphorothioate (PS) CpG ODNs on protection against murine
      allergic asthma in vivo. METHODS: Balb/c mice were sensitized to ovalbumin by
      intraperitoneal injection with or without CpG ODNs (PS CpG ODNs, PE CpG ODNs, and
      those with 3' dG(6)-run) and subsequently challenged with ovalbumin. We evaluated
      airway hyperresponsiveness, eosinophil proportion in bronchoalveolar lavage
      fluid, airway inflammation, and ovalbumin-specific antibody responses. RESULTS:
      The conjugation of a 3' dG(6)-run to PE CpG ODNs enhanced the production of IFN
      gamma from ovalbumin-specific T(H) cells and prevented the development of asthma
      in terms of airway hyperresponsiveness, airway eosinophilia, and ovalbumin
      specific IgE responses; these effects were comparable to those of PS CpG ODNs.
      Enhanced effects of the 3' dG(6)-run were also observed in PS CpG ODNs, though
      they were lower than those in PE CpG ODNs. CONCLUSION: This study suggests that
      conjugation of a 3' dG(6)-run to CpG ODNs might provide an effective method for
      immune modulation of allergic asthma.

PMID- 11590384
TI  - Blunting airway eosinophilic inflammation results in a decreased airway
      neutrophil response to inhaled LPS in patients with atopic asthma: a role for
      CD14.
AB  - Recent data demonstrate that atopic inflammation might enhance airway responses
      to inhaled LPS in individuals with atopic asthma by increasing CD14 expression on
      airway macrophages. We sought to determine whether blunting airway eosinophilic
      inflammation decreases CD14 expression and the subsequent airway
      polymorphonuclear neutrophil (PMN) response to inhaled LPS in subjects with
      atopic asthma. Twelve such subjects underwent a 2-week, placebo-controlled trial
      of inhaled steroid (440 microg fluticasone propionate [FP] twice per day); this
      was followed 48 hours later by an inhaled LPS (5 microg) challenge. A comparison
      of LPS-induced inflammatory cells in sputum, CD14 expression, and methacholine
      responsiveness with FP or placebo was conducted. Flow cytometry was used to
      analyze membrane-bound CD14 expression (mean fluorescence intensity) on sputum
      macrophages. We report that 48 hours before inhaled LPS challenge (baseline), FP
      significantly blunted airway eosinophils (cells per milligram; P =.04) and mCD14
      expression (mean fluorescence intensity; P =.03) but did not decrease the number
      of PMNs (cells per milligram). Six hours after LPS challenge, airway PMNs and
      mCD14 expression were significantly decreased for FP in comparison with placebo
      (P =.04). Our data suggest that decreasing airway allergic inflammation with
      corticosteroids results in both decreased expression of CD14 on airway monocytic
      cells and a decreased PMN response to inhaled LPS.

PMID- 11590385
TI  - Functional expression of chemokine receptor 2 by normal human eosinophils.
AB  - BACKGROUND: Within the granulocytes, the CC chemokines preferentially activate
      basophils and eosinophils on binding to chemokine receptors (CCRs). In vivo
      administration of neutralizing anti-monocyte chemoattractant protein 1 (MCP-1)
      antibodies can block accumulation of eosinophils in the lungs of antigen
      challenged animals. OBJECTIVE: We studied a panel of chemokines for chemotactic
      activity in normal human eosinophils from healthy donors with a special focus on
      MCP-1, identified the respective receptor required for the biological response of
      eosinophils, and investigated mediators used for signal transduction. METHODS:
      Cells were enriched by magnetic cell sorting. Receptor expression in eosinophils
      was shown by RT-PCR and fluorescence-activated cell sorting. The biological
      response was tested in chemotaxis and calcium mobilization assays. RESULTS:
      Eosinophils have detectable mRNA for CCR2, and the receptor protein is expressed
      on cell surfaces. MCP-1 induces chemotaxis and calcium mobilization in
      eosinophils. The chemotactic activity of MCP-1 revealed a double-peaked dose
      response curve; one of the peaks is abolished by addition of a blocking antibody
      to CCR2, but it is insensitive to blocking of CCR1 or CCR3. Specific enzyme
      inhibitors ruled out signaling characteristics of CCR2 in eosinophils.
      CONCLUSION: Normal human eosinophils express functional CCR2 on cell surfaces.

PMID- 11590386
TI  - Standardized extracts from Chinese herbs induce IL-10 production in human
      monocyte-derived dendritic cells and alter their differentiation in vitro.
AB  - BACKGROUND: The efficacy of traditional Chinese medicine (TCM) as a treatment for
      atopic dermatitis has been evaluated in clinical trials. Until now, the
      underlying mechanism of this treatment has remained completely elusive; this is
      particularly true of its putative effects on dendritic cells (DCs), which might
      play a pivotal role in the disease. OBJECTIVE: We investigated the influence of a
      standardized extract from 10 Chinese herbs that was successfully used in clinical
      trials on the generation of monocyte-derived DCs from atopic donors. METHODS:
      Detailed phenotypic and functional exploration of DCs generated in the presence
      of IL-4 and GM-CSF and treated with different concentrations of TCM or a placebo
      control was performed. RESULTS: TCM profoundly affected the morphology and
      phenotype of the developing DCs. They lost their typical dendritic morphology and
      decreased their expression of CD1a as well as the low-affinity IgE receptor CD23.
      Most importantly, TCM-exposed DCs exhibited a diminished stimulatory activity
      toward autologous antigen-specific and allogeneic T cells while secreting high
      amounts of IL-10. CONCLUSION: TCM induces immunopharmacologic alterations on DCs
      from atopic donors in vitro. These alterations might account, at least in part,
      for the therapeutic effect of this treatment in AD in vivo.

PMID- 11590387
TI  - IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin
      dependent mechanism.
AB  - BACKGROUND: IL-13 induces several characteristic features of asthma, including
      airway eosinophilia, airway hyperresponsiveness, and mucus overproduction;
      however, the mechanisms involved are largely unknown. OBJECTIVE: We hypothesized
      that IL-13-induced inflammatory changes in the lung were dependent in part on IL
      5 and eotaxin, two eosinophil-selective cytokines. METHODS: Recombinant murine IL
      13 was repeatedly administered to the lung by intranasal delivery until the
      characteristic features of asthma developed. To analyze the role of IL-5 and
      eotaxin, we subjected eotaxin gene-targeted, IL-5 gene-targeted, eotaxin/IL-5
      double-deficient, IL-5 transgenic, and wild-type mice of the Balb/C background to
      the experimental regime. RESULTS: The induction of IL-13-mediated airway
      eosinophilia was found to occur independently of eosinophilia in the blood or
      bone marrow, indicating that IL-13-induced airway inflammation is primarily
      mediated by local effects of IL-13 in the lung. Eosinophil recruitment into both
      the lung tissue and bronchoalveolar lavage fluid was markedly attenuated in IL-5
      deficient mice in comparison with wild-type controls. Accordingly, IL-13 delivery
      to IL-5 transgenic mice resulted in a large increase in airway eosinophils in
      comparison with wild-type mice. Interestingly, IL-13-induced eosinophilia in the
      bronchoalveolar lavage fluid of eotaxin-deficient mice was not impaired; however,
      these same mice failed to mount a significant tissue eosinophilia in response to
      IL-13. Finally, IL-13-induced mucus production was not affected by the presence
      of IL-5 or eotaxin, suggesting that IL-13-induced mucus secretion is
      mechanistically dissociated from airway eosinophilia. CONCLUSION: Selective
      components of the IL-13-induced asthma phenotype--airway eosinophilia but not
      mucus secretion--are differentially regulated by IL-5 and eotaxin. IL-5 is
      required for IL-13 to induce eosinophilia throughout the lung, whereas eotaxin
      regulates the distribution of airway eosinophils.

PMID- 11590388
TI  - Analysis of Ig subclass deficiency: First reported case of IgG2, IgG4, and IgA
      deficiency caused by deletion of C alpha 1, psi C gamma, C gamma 2, C gamma 4,
      and C epsilon in a Mongoloid patient.
AB  - BACKGROUND: The cause of Ig class or subclass deficiencies has been unclear
      except for IgH gene deletions and a homozygous 1-base insertion (1793insG) in C
      gamma 2 exon 4 of IgG2 deficiency. In addition, there are no reports that IgH
      gene deletions are found in patients who are Mongoloid (a category that includes
      most of the people of Asia, such as the Japanese, Chinese, Indonesians and
      Malaysians). OBJECTIVE: To investigate the cause of Ig subclass deficiency, we
      extensively investigated 4 Japanese patients with low serum IgG2 levels. Patient
      1 was a 23-month-old girl whose serum IgG2, IgG4, and IgA levels were under the
      detection limits; she also had idiopathic thrombocytopenic purpura. Patient 2 was
      a 5-year-old boy whose serum IgG2 level was under the detection limit. Patient 3
      was a 14-month-old boy whose serum IgG2 and IgG4 levels were under the detection
      limits. Patient 4 was 3-year-old girl whose IgG2 level was low and whose IgA
      level was under the detection limit. METHODS: DNA was extracted from neutrophils,
      and Southern blot analysis was performed. RESULTS: Southern blot analysis
      revealed that patient 1 had lost the C alpha 1, psi C gamma, C gamma 2, C gamma
      4, and C epsilon genes and was a homozygous carrier of the deletion described
      above. Her mother was of the heterozygous genotype. DNA from patients 2, 3, and 4
      revealed no deletions in comparison with control DNA. CONCLUSION: This is a
      report of the first case of a Mongoloid in whom IgG2, IgG4, and IgA deficiency
      was caused by deletion of C alpha 1, psi C gamma, C gamma 2, C gamma 4, and C
      epsilon. Our finding contributes to investigations of Ig subclass deficiency.

PMID- 11590389
TI  - Expression of IL-18 mRNA and secretion of IL-18 are reduced in monocytes from
      patients with atopic dermatitis.
AB  - BACKGROUND: IL-18 has been found to be an IFN-gamma-inducing factor that plays an
      important role in T(H)1 cell activation. Recently, IL-18 has also been found to
      enhance a T(H)2 cellular response in a specific setting. OBJECTIVE: The aim of
      this study was to elucidate the role of monocytes and soluble factors, with
      special focus on IL-18, in the pathogenesis of atopic dermatitis (AD). METHODS:
      The release of cytokines from PBMCs and purified monocytes was measured through
      use of ELISA; mRNA expression was evaluated by RT-PCR. The results from patients
      with AD were compared with those from healthy controls. RESULTS: IL-18 secretion
      was reduced in both unstimulated and lipopolysaccharide-stimulated monocytes from
      patients with AD. The mRNA expression of IL-18 and IL-1 beta-converting enzyme
      was significantly reduced in unstimulated monocytes from patients with AD (P <.03
      and P <.01, respectively). Patients with AD had an elevated secretion of
      prostaglandin E(2) (PGE(2)) from unstimulated PBMCs (P <.001). The anti-PGE(2)
      antibody reversed the suppressive effect of PGE(2) on IL-18 secretion in
      unstimulated PBMCs from patients with AD. CONCLUSIONS: Decreased IL-18
      production, together with a significantly reduced IL-18 and ICE mRNA expression
      in unstimulated monocytes and elevated PGE(2) secretion from PBMCs, was
      associated with the pathogenesis of AD.

PMID- 11590390
TI  - Familial cold autoinflammatory syndrome: phenotype and genotype of an autosomal
      dominant periodic fever.
AB  - BACKGROUND: Familial cold autoinflammatory syndrome (FCAS), commonly known as
      familial cold urticaria, is a rare autosomal dominant inflammatory disorder with
      episodic symptoms precipitated by exposure to cold. OBJECTIVE: The goal of this
      study was to formulate clinical diagnostic criteria for FCAS in a large cohort in
      whom the diagnosis of FCAS was supported by genetic linkage to chromosome 1q44.
      METHODS: We assessed 45 affected and 68 unaffected members from 6 American
      families. DNA analysis was performed to confirm linkage to chromosome 1q44.
      Clinical characteristics were determined by means of analysis of detailed
      questionnaires and medical histories. RESULTS: Pedigree and genetic analyses
      confirmed autosomal dominant transmission and linkage to chromosome 1q44 in all
      families. The most consistent symptoms during attacks were rash (100%), fever
      (93%), arthralgia (96%), and conjunctivitis (84%). Age of onset was within the
      first 6 months of life in 95% of affected subjects. The average delay between
      cold exposure and onset of symptoms was 2.5 hours, and the average duration of an
      episode was 12 hours. Renal disease with amyloidosis occurs infrequently in FCAS
      (2%). CONCLUSION: The most consistent clinical characteristics of FCAS that
      discriminate it from other periodic fevers are association with cold exposure,
      conjunctivitis, age of onset, duration of episodes, and an autosomal dominant
      inheritance pattern. On the basis of the analysis of genotype and phenotype of
      FCAS, we formulated clinical diagnostic criteria that can be used to distinguish
      FCAS from other hereditary periodic fever syndromes.

PMID- 11590391
TI  - Hev b 7 is a Hevea brasiliensis protein associated with latex allergy in children
      with spina bifida.
AB  - BACKGROUND: In addition to their disease-associated handicaps, patients with
      spina bifida (SB) are at high risk of developing latex allergy. Individuals with
      SB represent a special group of latex-allergic patients, inasmuch as their IgE
      binding patterns differ from those of other populations of latex-allergic
      individuals. Two allergens strongly associated with latex allergy in patients
      with SB--Hev b 1 and Hev b 3--have already been identified. OBJECTIVE: We
      intended to identify a predominant IgE-binding band--in addition to Hev b 1 and 3
      -at 43 kDa in a study population of 38 latex-allergic (IgE antibodies to latex
      and symptoms on provocation with latex gloves) and 15 latex-sensitized (IgE
      antibodies to latex but no symptoms on provocation) children with SB (mean age,
      12.3 years) and to determine its frequency of recognition. METHODS: Sera of latex
      sensitized or latex-allergic patients with SB were tested on latex C extract
      containing natural Hev b 1, Hev b 3, and Hev b 7 and with the recombinant 43-kDa
      Hev b 7 in immunoblot and inhibition studies. RESULTS: Natural Hev b 1 was
      recognized by 82% and natural Hev b 3 by 79% of the latex-allergic children with
      SB. In addition to some other proteins, 15 (39.5%) of 38 latex-allergic and 2
      (13%) of 5 latex-sensitized children with SB revealed IgE binding to a 43-kDa
      band in the latex protein extract. We identified this 43-kDa IgE-binding band as
      natural Hev b 7 by immunoblotting and inhibition experiments using recombinant
      Hev b 7. CONCLUSION: From these data, we conclude that Hev b 7, the patatin-like
      Hevea latex protein, is the third SB-associated latex allergen. Future
      immunotherapy for latex-allergic individuals with SB will have to include Hev b 7
      in addition to Hev b 1 and Hev b 3.

PMID- 11590392
TI  - Outcomes of a natural rubber latex control program in an Ontario teaching
      hospital.
AB  - BACKGROUND: Allergy to natural rubber latex (NRL) has been frequently reported in
      health care workers. However, there is little published evidence of the outcome
      of hospital intervention programs to reduce exposure and detect cases of
      sensitization early. OBJECTIVE: This study assesses the effects of intervention
      to reduce NRL allergy in an Ontario teaching hospital with approximately 8000
      employees. METHODS: A retrospective review assessed annual numbers of employees
      visiting the occupational health clinic, allergy clinic, or both for
      manifestations of NRL allergy compared with the timing of introduction of
      intervention strategies, such as worker education, voluntary medical
      surveillance, and hospital conversion to low-protein, powder-free NRL gloves.
      RESULTS: The number of workers identified with NRL allergy rose annually, from 1
      in 1988 to 6 in 1993. When worker education and voluntary medical surveillance
      were introduced in 1994, a further 25 workers were identified. Nonsterile gloves
      were changed to low-protein, powder-free NRL gloves in 1995: Diagnoses fell to 8
      workers that year, and 2 of the 3 nurses who had been off work because of asthma
      anaphylaxis were able to return to work with personal avoidance of NRL products.
      With a change to lower protein, powder-free NRL sterile gloves in 1997, allergy
      diagnoses fell to 3, and only 1 new case was identified subsequently up to May
      1999. No increased glove costs were incurred as a result of consolidated glove
      purchases. CONCLUSIONS: This program to reduce NRL allergy in employees was
      effectively achieved without additional glove costs while reducing expenses from
      time off work and workers' compensation claims.

PMID- 11590393
TI  - Wheat omega-5 gliadin is a major allergen in children with immediate allergy to
      ingested wheat.
AB  - BACKGROUND: Sensitization to wheat by ingestion can lead to food allergy symptoms
      and wheat-dependent, exercise-induced anaphylaxis. Sensitization by inhalation
      causes bakers' asthma and rhinitis. Wheat allergens have been characterized at
      the molecular level in bakers' asthma and in wheat-dependent, exercise-induced
      anaphylaxis, in which omega-5 gliadin (Tri a 19) is a major allergen. However,
      little information is available regarding allergens responsible for
      hypersensitivity reactions to ingested wheat in children. OBJECTIVE: The aim of
      this study was to examine whether children with allergy to ingested wheat have
      IgE antibodies to omega-5 gliadin. METHODS: Sera were obtained from 40 children
      (mean age, 2.5 years; range, 0.7-8.2 years) with suspected wheat allergy who
      presented with atopic dermatitis and/or gastrointestinal and/or respiratory
      symptoms. Wheat allergy was diagnosed with open or double-blinded, placebo
      controlled oral wheat challenge. Wheat omega-5 gliadin was purified by reversed
      phase chromatography, and serum IgE antibodies to omega-5 gliadin were measured
      by means of ELISA. In vivo reactivity was studied by skin prick testing. Control
      sera were obtained from 22 children with no evidence of food allergies. RESULTS:
      In oral wheat challenge, 19 children (48%) reacted with immediate and 8 children
      (20%) with delayed hypersensitivity symptoms. Sixteen (84%) of the children with
      immediate symptoms had IgE antibodies to purified omega-5 gliadin in ELISA. In
      contrast, IgE antibodies to omega-5 gliadin were not detected in any of the
      children with delayed or negative challenge test results or in the control
      children. The diagnostic specificity and positive predictive value of omega-5
      gliadin ELISA were each 100% for immediate challenge reactions. Skin prick
      testing with omega-5 gliadin was positive in 6 of 7 children with immediate
      challenge symptoms and negative in 2 children with delayed challenge symptoms.
      CONCLUSION: The results of this study show that omega-5 gliadin is a significant
      allergen in young children with immediate allergic reactions to ingested wheat.
      IgE testing with omega-5 gliadin could be used to reduce the need for oral wheat
      challenges in children.

PMID- 11590394
TI  - Food Allergy Herbal Formula-1 (FAHF-1) blocks peanut-induced anaphylaxis in a
      murine model.
AB  - BACKGROUND: Peanut allergy is a major cause of fatal and near-fatal anaphylactic
      reactions to foods. There is no curative therapy for this condition. Traditional
      Chinese medicines have been reported to have antiallergic properties, which might
      be useful for treating peanut allergy. OBJECTIVE: The purpose of this study was
      to investigate the effects of a Chinese herbal formula, FAHF-1, on peanut
      anaphylactic reactions in a mouse model of peanut allergy. METHODS: Mice were
      sensitized with freshly ground whole peanut in the presence of cholera toxin and
      boosted 1 and 3 weeks later. FAHF-1 treatment was initiated 1 week later and
      continued for 7 weeks. After treatment, mice were challenged with peanut, and
      anaphylactic symptoms, body temperatures, and plasma histamine and IgE levels
      were measured. T-cell proliferative responses and cytokine production were also
      determined. RESULTS: FAHF-1 completely blocked peanut-induced anaphylactic
      symptoms and markedly reduced mast cell degranulation and histamine release.
      Peanut-specific serum IgE levels were significantly reduced by 2 weeks of
      treatment at the time of challenge, and they remained lower 4 weeks after
      discontinuation of treatment. FAHF-1 significantly reduced peanut-induced
      lymphocyte proliferation as well as IL-4, IL-5, and IL-13 synthesis but not IFN
      gamma synthesis. No toxic effects on liver or kidney functions were observed, nor
      was there any overall immune suppression. CONCLUSION: FAHF-1 protected peanut
      sensitized mice from anaphylactic reactions and significantly reversed
      established IgE-mediated peanut allergy. This suggests that FAHF-1 might prove
      valuable for the treatment of peanut allergy.

PMID- 11590395
TI  - Isolation and characterization of barley lipid transfer protein and protein Z as
      beer allergens.
AB  - Beer has recently been implicated as the causative agent of contact urticaria and
      severe IgE-mediated anaphylaxis. However, no allergen from beer has as yet been
      isolated and characterized. Two major components of 45 kd and 9 kd were detected
      in crude protein preparations from beer. Both components were purified; they were
      identified as barley protein Z(4) (45 kd) and lipid transfer protein 1 (LTP1; 9
      kd). Protein Z(4) was recognized by the 4 individual sera tested but provoked
      weak positive responses to skin testing in 2 of 4 beer-allergic patients.
      Purified LTP1 showed reactivity with 3 of 4 individual sera and induced strong
      positive skin prick responses in all 4 patients tested. Barley LTP1 and protein
      Z(4) have been identified as the main beer allergens.

PMID- 11590396
TI  - Allergic reactions after ingestion of erythritol-containing foods and beverages.

PMID- 11590397
TI  - Allergenic cross-reactivity between nickel and chromium salts in electroplating
      induced asthma.

PMID- 11590398
TI  - Effects of cefuroxime axetil on Staphylococcus aureus colonization and
      superantigen production in atopic dermatitis.

PMID- 11590399
TI  - Fel d 1 levels in domestic living rooms are not related to cat color or hair
      length.

PMID- 11590400
TI  - Allergenic risk from novel plants is very important and difficult to predict.

PMID- 11590402
TI  - Allergenicity of cry9c: an unresolved issue.

PMID- 11590404
TI  - Corticotropin-releasing hormone promotes blastocyst implantation and early
      maternal tolerance.
AB  - The semi-allograft embryo in the blastocyst stage implants itself in the
      endometrium, yet no immune rejection processes are activated. Embryonic
      trophoblast and maternal decidua produce corticotropin-releasing hormone (CRH)
      and express Fas ligand (FasL), a proapoptotic cytokine. We found that antalarmin,
      a CRH receptor type 1 antagonist, decreased FasL expression and promoted
      apoptosis of activated T lymphocytes, an effect which was potentiated by CRH and
      inhibited by antalarmin. Female rats treated with antalarmin showed a marked
      decrease in implantation sites and live embryos and diminished endometrial FasL
      expression. Embryos from mothers that lacked T cells or from syngeneic matings
      were not rejected when the mothers were given antalarmin. These findings
      suggested that locally produced CRH promotes implantation and maintenance of
      early pregnancy primarily by killing activated T cells.

PMID- 11590405
TI  - Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells.
AB  - In vivo models have shown that tissue-restricted antigen may be captured by bone
      marrow-derived cells and cross-presented for the tolerization of CD8+ T cells.
      Although these studies have shown peripheral tolerization of CD8+ T cells, the
      mechanism of antigen transfer and the nature of the antigen-presenting cell (APC)
      remain undefined. We report here the establishment of an in vitro system for the
      study of cross-tolerance and show that dendritic cells (DCs) phagocytose
      apoptotic cells and tolerize antigen-specific CD8+ T cells when cognate CD4+ T
      helper cells are absent. Using this system, we directly tested the "two-signal"
      hypothesis for the regulation of priming versus tolerance. We found that the same
      CD83+ myeloid-derived DCs were required for both cross-priming and cross
      tolerance. These data suggested that the current model for peripheral T cell
      tolerance, "signal 1 in the absence of signal 2", requires refinement: the
      critical checkpoint is not DC maturation, but instead the presence of a third
      signal, which is active at the DC-CD4+ T cell interface.

PMID- 11590407
TI  - Immunophilin ligand FK506 is neuroprotective for penile innervation.

PMID- 11590408
TI  - US throws money at TSE research.

PMID- 11590410
TI  - Stem cell losses and gains in the US.

PMID- 11590411
TI  - Prostate cancer prevention trial launched.

PMID- 11590412
TI  - R&D toxicity test to be eliminated.

PMID- 11590415
TI  - Ralph Steinman.

PMID- 11590414
TI  - Pfizer in "unethical" trial suit.

PMID- 11590416
TI  - Laskers for 2001: knockout mice and test-tube babies.

PMID- 11590418
TI  - The cultural mouse.

PMID- 11590419
TI  - Forty years with homologous recombination.

PMID- 11590420
TI  - Generating mice with targeted mutations.

PMID- 11590421
TI  - The bumpy road to human in vitro fertilization.

PMID- 11590422
TI  - The wonder that is global health.

PMID- 11590424
TI  - Cannabinoid activity curtails cocaine craving.

PMID- 11590425
TI  - The alternative to penicillins.

PMID- 11590426
TI  - Turning WAT into BAT gets rid of fat.

PMID- 11590427
TI  - Epilepsy and all that jazz.

PMID- 11590428
TI  - Plugging the leaks.

PMID- 11590429
TI  - A close look at the ends of BRCA1.

PMID- 11590430
TI  - NO, SNO and low O2.

PMID- 11590431
TI  - Linking ubiquitin, parkin and synphilin-1.

PMID- 11590433
TI  - Ferredoxin reductase affects p53-dependent, 5-fluorouracil-induced apoptosis in
      colorectal cancer cells.
AB  - Loss of p53 gene function, which occurs in most colon cancer cells, has been
      shown to abolish the apoptotic response to 5-fluorouracil (5-FU). To identify
      genes downstream of p53 that might mediate these effects, we assessed global
      patterns of gene expression following 5-FU treatment of isogenic cells differing
      only in their p53 status. The gene encoding mitochondrial ferredoxin reductase
      (protein, FR; gene, FDXR) was one of the few genes significantly induced by p53
      after 5-FU treatment. The FR protein was localized to mitochondria and suppressed
      the growth of colon cancer cells when over-expressed. Targeted disruption of the
      FDXR gene in human colon cancer cells showed that it was essential for viability,
      and partial disruption of the gene resulted in decreased sensitivity to 5-FU
      induced apoptosis. These data, coupled with the effects of pharmacologic
      inhibitors of reactive oxygen species, indicate that FR contributes to p53
      mediated apoptosis through the generation of oxidative stress in mitochondria.

PMID- 11590434
TI  - Immune-mediated eradication of tumors through the blockade of transforming growth
      factor-beta signaling in T cells.
AB  - Despite the existence of tumor-specific antigens and demonstrated presence of
      tumor-specific immune cells, the majority of tumors manage to avoid immune
      mediated destruction. Various mechanisms have been suggested for tumor evasion
      from immune response. One such mechanism is thought to be mediated by
      transforming growth factor-beta (TGF-beta), an immunosuppressive cytokine found
      at the site of most tumors. We demonstrate here that T-cell-specific blockade of
      TGF-beta signaling allows the generation of an immune response capable of
      eradicating tumors in mice challenged with live tumor cells. In addition, we
      provide mechanisms through which abrogation of TGF-beta signaling leads to the
      enhancement of anti-tumor immunity. Our data indicate that T-cell-specific
      blockade of TGF-beta signaling has strong therapeutic potential to shift the
      balance of the immune response in favor of anti-tumor immunity.

PMID- 11590435
TI  - Heparin-binding protein (HBP/CAP37): a missing link in neutrophil-evoked
      alteration of vascular permeability.
AB  - Polymorphonuclear leukocyte infiltration into tissues in host defense and
      inflammatory disease causes increased vascular permeability and edema formation
      through unknown mechanisms. Here, we report the involvement of a paracrine
      mechanism in neutrophil-evoked alteration in endothelial barrier function. We
      show that upon neutrophil adhesion to the endothelial lining, leukocytic beta2
      integrin signaling triggers the release of neutrophil-borne heparin-binding
      protein (HBP), also known as CAP37/azurocidin, a member of the serprocidin family
      of neutrophil cationic proteins. HBP induced Ca++-dependent cytoskeletal
      rearrangement and intercellular gap formation in endothelial-cell monolayers in
      vitro, and increased macromolecular efflux in microvessels in vivo. Moreover,
      selective inactivation of HBP prevented the neutrophils from inducing endothelial
      hyperpermeability. Our data suggest a fundamental role of neutrophil-derived HBP
      in the vascular response to neutrophil trafficking in inflammation. Targeting
      this molecule in inflammatory disease conditions offers a new strategy for
      prevention of endothelial barrier dysfunction caused by misdirected leukocyte
      activation.

PMID- 11590436
TI  - Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1.
AB  - All nuclear-encoded mRNAs contain a 5' cap structure (m7GpppN, where N is any
      nucleotide), which is recognized by the eukaryotic translation initiation factor
      4E (eIF4E) subunit of the eIF4F complex. The eIF4E-binding proteins constitute a
      family of three polypeptides that reversibly repress cap-dependent translation by
      binding to eIF4E, thus preventing the formation of the eIF4F complex. We
      investigated the biological function of 4E-BP1 by disrupting its gene (Eif4ebp1)
      in the mouse. Eif4ebp1-/- mice manifest markedly smaller white fat pads than wild
      type animals, and knockout males display an increase in metabolic rate. The
      males' white adipose tissue contains cells that exhibit the distinctive
      multilocular appearance of brown adipocytes, and expresses the uncoupling protein
      1 (UCP1), a specific marker of brown fat. Consistent with these observations,
      translation of the peroxisome proliferator-activated receptor-gamma co-activator
      1 (PGC1), a transcriptional co-activator implicated in mitochondrial biogenesis
      and adaptive thermogenesis, is increased in white adipose tissue of Eif4ebp1-/-
      mice. These findings demonstrate that 4E-BP1 is a novel regulator of adipogenesis
      and metabolism in mammals.

PMID- 11590437
TI  - Regulation of pancreatic beta-cell growth and survival by the serine/threonine
      protein kinase Akt1/PKBalpha.
AB  - The physiological performance of an organ depends on an interplay between changes
      in cellular function and organ size, determined by cell growth, proliferation and
      death. Nowhere is this more evident than in the endocrine pancreas, where
      disturbances in function or mass result in severe disease. Recently, the insulin
      signal-transduction pathway has been implicated in both the regulation of hormone
      secretion from beta cells in mammals as well as the determination of cell and
      organ size in Drosophila melanogaster. A prominent mediator of the actions of
      insulin and insulin-like growth factor 1 (IGF-1) is the 3'-phosphoinositide
      dependent protein kinase Akt, also known as protein kinase B (PKB). Here we
      report that overexpression of active Akt1 in the mouse beta cell substantially
      affects compartment size and function. There was a significant increase in both
      beta-cell size and total islet mass, accompanied by improved glucose tolerance
      and complete resistance to experimental diabetes.

PMID- 11590438
TI  - Targeted disruption of inducible nitric oxide synthase protects against obesity
      linked insulin resistance in muscle.
AB  - Inducible nitric oxide synthase (iNOS) is induced by inflammatory cytokines in
      skeletal muscle and fat. It has been proposed that chronic iNOS induction may
      cause muscle insulin resistance. Here we show that iNOS expression is increased
      in muscle and fat of genetic and dietary models of obesity. Moreover, mice in
      which the gene encoding iNOS was disrupted (Nos2-/- mice) are protected from high
      fat-induced insulin resistance. Whereas both wild-type and Nos2-/- mice developed
      obesity on the high-fat diet, obese Nos2-/- mice exhibited improved glucose
      tolerance, normal insulin sensitivity in vivo and normal insulin-stimulated
      glucose uptake in muscles. iNOS induction in obese wild-type mice was associated
      with impairments in phosphatidylinositol 3-kinase and Akt activation by insulin
      in muscle. These defects were fully prevented in obese Nos2-/- mice. These
      findings provide genetic evidence that iNOS is involved in the development of
      muscle insulin resistance in diet-induced obesity.

PMID- 11590440
TI  - A cannabinoid mechanism in relapse to cocaine seeking.
AB  - Treatment of cocaine addiction is hampered by high rates of relapse even after
      prolonged drug abstinence. This relapse to compulsive cocaine use can be
      triggered by re-exposure to cocaine, by re-exposure to stimuli previously
      associated with cocaine or by exposure to stress. In laboratory rats, similar
      events reinstate cocaine seeking after prolonged withdrawal periods, thus
      providing a model to study neuronal mechanisms underlying the relapse to cocaine.
      The endocannabinoid system has been implicated in a number of neuropsychiatric
      conditions, including drug addiction. The active ingredient of marijuana, Delta9
      tetrahydrocannabinol, activates the mesolimbic dopamine (DA) reward system and
      has rewarding effects in preclinical models of drug abuse. We report here that
      the synthetic cannabinoid agonist, HU210 (ref. 13), provokes relapse to cocaine
      seeking after prolonged withdrawal periods. Furthermore, the selective CB1
      receptor antagonist, SR141716A (ref. 14), attenuates relapse induced by re
      exposure to cocaine-associated cues or cocaine itself, but not relapse induced by
      exposure to stress. These data reveal an important role of the cannabinoid system
      in the neuronal processes underlying relapse to cocaine seeking, and provide a
      rationale for the use of cannabinoid receptor antagonists for the prevention of
      relapse to cocaine use.

PMID- 11590439
TI  - Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1:
      implications for Lewy-body formation in Parkinson disease.
AB  - Parkinson disease is a common neurodegenerative disorder characterized by the
      loss of dopaminergic neurons and the presence of intracytoplasmic-ubiquitinated
      inclusions (Lewy bodies). Mutations in alpha-synuclein (A53T, A30P) and parkin
      cause familial Parkinson disease. Both these proteins are found in Lewy bodies.
      The absence of Lewy bodies in patients with parkin mutations suggests that parkin
      might be required for the formation of Lewy bodies. Here we show that parkin
      interacts with and ubiquitinates the alpha-synuclein-interacting protein,
      synphilin-1. Co-expression of alpha-synuclein, synphilin-1 and parkin result in
      the formation of Lewy-body-like ubiquitin-positive cytosolic inclusions. We
      further show that familial-linked mutations in parkin disrupt the ubiquitination
      of synphilin-1 and the formation of the ubiquitin-positive inclusions. These
      results provide a molecular basis for the ubiquitination of Lewy-body-associated
      proteins and link parkin and alpha-synuclein in a common pathogenic mechanism
      through their interaction with synphilin-1.

PMID- 11590441
TI  - The analysis of costimulatory receptor signaling cascades in normal T lymphocytes
      using in vitro gene transfer and reporter gene analysis.
AB  - Ligation of the antigen receptor and costimulatory receptors on the surface of T
      lymphocytes initiates intracellular signals that regulate cell-cycle progression
      and cell differentiation. To effectively manipulate the activation of T cells for
      immunotherapeutic applications, it will be important to understand how these
      signaling pathways are integrated to control specific gene transcription events.
      Here we describe a novel transient transfection procedure that efficiently
      introduces DNA into non-dividing normal human and murine T lymphocytes while
      maintaining high cell viability. Using this technique, reporter genes can be
      introduced to characterize intracellular signaling pathways that regulate
      specific gene transcription events in normal T-lymphocyte populations. We show
      that the CD28 receptor can be differentially coupled to downstream signaling
      pathways in different T-lymphocyte populations. In addition, we demonstrate that
      a gene encoding a tagged constitutively active mitogen-activated kinase kinase-1
      protein can be transfected and rapidly expressed to regulate the expression of
      Bcl-2 in normal thymocytes.

PMID- 11590442
TI  - Adoptive tumor therapy with T lymphocytes enriched through an IFN-gamma capture
      assay.
AB  - Successful adoptive T-cell therapy has been demonstrated in viral disease and
      selected forms of cancer. However, it is limited by the difficulty to efficiently
      isolate and amplify autologous tumor-reactive T-cell clones. Tetramers of major
      histocompatibility complex (MHC) class I and peptide have facilitated the
      characterization of CD8+ T cells specific for tumor-associated antigens. However,
      for adoptive T-cell therapy, MHC-tetramers have limitations: they require
      knowledge of tumor antigens, which is often not available; they select T cells
      with a single specificity, thereby posing risk for selection of tumor escape
      variants; they do not select for function, so that T cells may be anergic when
      isolated from cancer patients; and they do not allow the isolation of CD4+ T
      cells that can be essential for tumor rejection. Because interferon (IFN)-gamma
      is essential for tumor rejection, we isolated live T cells based on their IFN
      gamma production. IFN-gamma secreted by previously activated T cells is retained
      on the cell surface, allowing their specific isolation and expansion. We show
      here that IFN-gamma+ but not IFN-gamma- T cells from tumor-immunized mice are
      cytolytic and mediate tumor rejection upon adoptive transfer. Importantly, tumor
      specific T cells can be enriched from lymphocytes infiltrating human renal cell
      carcinoma by the IFN-gamma capture assay.

PMID- 11590445
TI  - Global directions for reforming health systems and expanding insurance. What is
      suitable for the Arab Gulf countries?
AB  - Most countries are exploring and implementing reforms of their health care
      systems. The Arab countries in the Gulf are no exception after establishing
      modern governmental health care systems accessible to all and free of charge.
      Current problems of the Arab systems include financial, managerial and quality
      issues. The private sector in these countries has no defined national role and is
      gowing abruptly and unplanned. The paper presents the major global health reform
      directions, analyzing the current activities in the Arab Gulf countries and
      proposing certain practical relevant approaches for health reform, and expansion
      of insurance in these activites.

PMID- 11590446
TI  - Incidence of uterine rupture in a Teaching Hospital, Sudan.
AB  - OBJECTIVE: This study aims to document the experience of uterine rupture as a
      serious common complication of pregnancy in some developing countries like Sudan.
      The study is also aimed at reviewing the main contributing factors so as to draw
      broad lines for a strategy of prevention. METHODS: A retrospective study carried
      out at Medani Teaching Hospital, Medani City, Sudan. Case notes were reviewed for
      all patients with uterine rupture from 1st January 1992 through 31st of December
      1997. The data was analyzed and the literature was reviewed to compare the
      results of similar studies. RESULTS: Out of the total number of deliveries in
      that period (n=21190), 86 cases were diagnosed to have uterine rupture giving an
      incidence of 1:246. The main contributing factor to uterine rupture identified in
      this study, was poor ante-natal care (64%). One most important direct cause of
      uterine rupture was previous cesarean section scar with or without cephalopelvic
      disproportion (n=39) (45%). Seventy-six cases, had complete rupture of uterus.
      Subtotal hysterectomy was carried out on 69 cases (80%) and 15 cases (17%) had
      uterine repair with bilateral tubal ligation. Three patients developed vesico
      vaginal fistula (3.5%). The ureter was iatrogenically severed in 2 cases (2%).
      There were 6 (7%) maternal deaths and 68 (79%) perinatal deaths. CONCLUSION: This
      study confirms the existence of a serious preventable obstetrical problem. Poor
      antenatal care, poor provision of health service and low socioeconomic standards,
      are the main factors contributing to uterine rupture. Those findings would
      suggest that both social and medical improvements will significantly improve
      survival in mothers with ruptured uterus and reduce the perinatal loss.

PMID- 11590447
TI  - Management of sacrococcygeal pilonidal disease.
AB  - OBJECTIVE: Many techniques have been described for the treatment of patients with
      sacrococcygeal pilonidal disease. No data exists, in relation to this disease
      within the Kingdom of Saudi Arabia. The aim of this paper is to evaluate our
      technique retrospectively for management of pilonidial disease with regard to
      cure and recurrence rates. METHODS: All patients treated at King Faisal
      Specialist Hospital with either pilonidal abscess or sinus between 1990 and 1998
      were identified from the colorectal database and details concerning their
      presentation, surgery and follow-up were obtained from the patients charts. Both
      patients with pilonidal sinus and abscess were managed by laying open. Patients
      were followed until their wounds had healed. RESULTS: Ninety-eight patients, 12
      females and 86 males were treated for pilonidal disease in an 8-year period. All
      patients were managed by laying open. Thirty-one had had previous surgery.
      Seventy-one presented with pilonidal sinus and 27 presented with pilonidal
      abscess. The mean length of history prior to presentation was 25 months. Thirty
      one patients had an average of 1.6 operations prior to surgery at King Faisal
      Specialist Hospital. The mean hospital stay was 5.4 days. The average time for
      healing following laying open was 2.4 months. Five patients developed recurrence
      following surgery at King Faisal Specialist Hospital 6%. Of the 67 patients who
      had their primary surgery at King Faisal Specialist Hospital, 2 patients
      developed recurrence 3%. The mean period of follow up was 6 months range (3-50
      months). CONCLUSION: "Laying open" should be the treatment of choice for patients
      with sacrococcygeal pilonidal disease irrespective of whether the patient
      presents acutely or electively. Cure rates are high and recurrence rates are low.
      There is no longer any place for the 2 stage management of pilonidal abscess.

PMID- 11590448
TI  - Serum sodium changes during and after transuretheral prostatectomy.
AB  - OBJECTIVE: This prospective study aims at determining the effect of transurethral
      resection of the prostate on serum sodium levels during and after the procedure.
      METHODS: One hundred consecutive unselected patients with prostatic obstructive
      symptoms over a period of 11 months underwent transurethral resection of the
      prostate using continuous flow irrigation with 1.5% glycine running from a height
      of 70 cm above the table level under epidural anesthesia and were given 1L of
      intravenous normal saline/hour during the procedure. Resection time ranged
      between 25 and 90 minutes (mean 32) and was less than 45 minutes in 91 patients
      (91%). No postoperative irrigation or diuretics were given and the patients were
      given food and liberal fluids immediately after the operation. RESULTS: Fifty
      four patients (54%) had intraoperative reduction of serum sodium ranging between
      2 and 7 mmol/L (mean 3.5), 18 of whom showed further drop of 2-10 mmol/L after 24
      hours (mean 3.4). Twenty-five patients (25%) did not have any intraoperative
      change in their serum sodium level, 6 of whom dropped their serum sodium 24 hours
      later. After 24 hours, 41 patients (41%) ended with serum sodium lower than their
      preoperative level by 2-12 mmol/L (mean 4%), 3 of whom had a drop of 10-12
      mmol/L. The reduction was manifested 24 hours after the procedure in 27 patients
      (27%). None of the patients had transurethral resection syndrome nor its
      prodromal manifestations. CONCLUSION: After transurethral resection of the
      prostate, hyponatremia can occur as late as 24 hours postoperatively. Short
      operative time, giving intravenous sodium supplement intraoperatively and
      avoiding postoperative irrigation were perhaps factors in avoiding drastic
      hyponatremia and transurethral resection syndrome in this prospective series of
      unselected patients.

PMID- 11590449
TI  - Chronic pelvic pain. Laparoscopic and cystoscopic findings.
AB  - OBJECTIVE: To study the laparoscopic and cystoscopic findings in women with
      chronic pelvic pain referred to the Gynecology Clinic at Sultan Qaboos University
      Hospital. METHODS: Women referred to Sultan Qaboos University Hospital, Sultanate
      of Oman from October 1998-September 2000 with pelvic pain of more than 6 months
      duration were clinically evaluated. Laparoscopic examination was always combined
      with cystoscopy. Bladder biopsy was performed only if there were doubts regarding
      the nature of pathology that was found. RESULTS: The mean age of the patients was
      31 years and mean parity was 3.0. The minimum duration of symptoms was 6 months,
      but one 3rd of the patients had pain for more than 2 years. Bladder symptoms were
      present in 50% and bowel symptoms in 25% of patients. Laparoscopic examination
      revealed pathological findings in 80% of the cases. Adhesions of the omentum to
      the uterus or to the laparotomy or laparoscopy scar were the most common
      pathology (50%). Cystoscopy revealed one case of trigonitis and one case of
      cystitis. CONCLUSION: Pelvic adhesions were the most common cause of pelvic pain
      in our study group. Cystoscopy was normal in most of the patients.

PMID- 11590450
TI  - Laparoscopy versus laparotomy management of tubal pregnancy.
AB  - OBJECTIVE: To compare laparoscopy versus laparotomy management of tubal pregnancy
      and the reproductive outcome. METHODS: A retrospective chart review of 81
      patients admitted for management of tubal pregnancy was carried out at Riyadh
      Armed Forces Hospital from January 1998 until January 2000. The patients were
      divided according to surgical procedure performed into: Group I (33 patients)
      laparoscopy and group II (48 patients) laparotomy. We evaluated pre and
      postoperative serum b-human chorionic gonadotrophin levels, total operating time,
      total blood loss or blood transfusion or both, duration of hospital stay,
      recurrence rates of ectopic pregnancy and future fertility outcome for all
      patients. RESULTS: No differences were found between both groups in patient age,
      parity, size of adnexal mass, condition at the time of presentation, site of
      tubal pregnancy, previous history of ectopic, pre and postoperative serum b-human
      chorionic gonadotrophin and the total operating time. There were significant
      reductions of total blood loss, number of blood transfusion units, and duration
      of hospital stay, in the laparoscopic group compared to the laparotomy group. A
      total of 54 patients desired pregnancy, 23 patients in the laparoscopy and 31
      patients in the laparotomy group. No significant differences were found in the
      fertility outcome between both groups. The rates of subsequent intrauterine
      pregnancy were 74% (17/23) in the laparoscopy group and 61%, (19/31) in the
      laparotomy group and the rates of subsequent ectopic pregnancy were 4% (1/23) in
      the laparoscopy group and 10% (3/31) in the laparotomy group. CONCLUSION:
      Laparoscopic treatment of ectopic pregnancy in hemodynamically stable patients
      offers major economic benefits superior to laparotomy in terms of less need for
      blood transfusion, shorter duration of hospital stay and convalescence.

PMID- 11590451
TI  - Drug resistance pulmonary tuberculosis in the Eastern Province of Saudi Arabia.
AB  - OBJECTIVE: To evaluate the prevalence and pattern of antituberculous drug
      resistance and patients with pulmonary tuberculosis in the Eastern Province and
      its impact on the tuberculosis control program. METHODS: Patients with pulmonary
      tuberculosis, proven by culture, admitted to Dammam Chest Hospital from November
      1993 through May 1996 were reviewed. Patients who had at least one documented
      isolate of mycobacterium tuberculosis resistant to at least one standard anti
      tuberculosis drug were identified. Medical records were reviewed and information
      was retrieved regarding age, sex, nationality, history of previous tuberculosis,
      human immune deficiency status, and results of direct smear and chest radiograph
      abnormalities. RESULTS: A total of 411 cases of culture positive pulmonary
      tuberculosis with drug susceptibility testing, were identified during the period
      mentioned, of these 123 (30%) were Saudi nationals and 228 (70%) were non-Saudis.
      Drug resistance to at least one drug was observed in 43 (10.5%) patients,
      resistance to isoniazid alone was observed in 25 (6%) patients, whereas
      resistance to rifampicin was noted in only one (0.2%) patient, and to
      streptomycin in 3 (1%) patients, multidrug resistance was observed in 11 (3%)
      patients. CONCLUSION: The study has shown that the overall drug resistance rate
      of 10.5% in the Eastern Province of Saudi Arabia is the lowest reported in the
      Kingdom, compared with Riyadh (13%), Taif (23%) and Gizan (44%). However, it
      appears to be similar to that reported in neighboring countries. In light of the
      study findings, and as per the recommendation of the World Health Organization,
      we suggest that a 4-drug regimen, as an initial treatment for pulmonary
      tuberculosis should be maintained, as resistance to isoniazid is still higher
      than the cut off value of 4%, and susceptibility testing for first line
      antituberculosis drugs should be carried out whenever possible. We also recommend
      applying stricter medical criteria for tuberculosis screening in newcomers, and
      for Saudi nationals, application of directly observed therapy should be a
      priority.

PMID- 11590452
TI  - Impact of national protocol on management of acute respiratory infections in
      children.
AB  - OBJECTIVE: To measure the impact of implementation of the national protocol on
      the prescribing patterns for acute respiratory infections among children
      attending a large primary health care center in Abha City. METHODS: This study
      was carried out during December of 1997 and February of 1998 in Abha City, Asir
      Region, Kingdom of Saudi Arabia. One quarter of the prescriptions which were
      issued in those 2 months were selected randomly and assessed for age, sex,
      diagnosis and the prescribed drugs before and after intensive training of the
      primary health care physicians on the implementation of the national protocol for
      acute respiratory infections. RESULTS: One hundred and forty five and 123
      prescriptions were selected and assessed pre and post the implementation of this
      protocol. Our findings showed a decrease in the prescription of antibiotics from
      53% to 33%, anti-cough drugs from 43.5% to 6%, and anti-histaminics from 20% to
      10%. CONCLUSION: Training on the national protocol and its implementation will
      decrease the rate of prescribing and misuse of unnecessary drugs such as
      antibiotics, anti-cough and anti-histamines.

PMID- 11590453
TI  - Physical activity profile of adult males in Riyadh City.
AB  - OBJECTIVE: To assess the patterns and determinants of physical activity among
      Saudi adult males living in Riyadh. METHODS: Self-administered questionnaires
      were filled out by 1333 randomly selected Saudi males 19 years and older, during
      the Fall of 1996. RESULTS: Over 53% of Saudi males were totally physically
      inactive, and another 27.5% were irregularly active. Only 19% of the entire
      sample were active on a regular basis. A curvilinear relationship was found
      between age and inactivity, with the middle age group the least active. Physical
      activity was lower among those who were married, work in the private sectors,
      working 2 shifts, less educated, or who had only one day off during the week.
      Time constraint seems to be the major contributing factor to inactivity, while
      maintaining health and losing weight were the most important reason for being
      physically active among Saudi males. CONCLUSION: The proportion of Saudi males
      who are at risk for inactivity is very high. Indeed, it is exceedingly higher
      than those who are at risk for hypertension, hypercholesterolemia, obesity, or
      cigarette smoking. Public policies are needed to encourage active living and
      discourage sedentary habits. Health care providers have an important role in
      promoting physical activity among the population.

PMID- 11590454
TI  - Vascular compromise associated with supracondylar fractures in children.
AB  - OBJECTIVE: Our aim was to study the significance of persistently absent radial
      pulse, with monophasic doppler flow after close reduction percutaneous pinning of
      displaced supracondylar fracture of humerus, and the need of early exploration of
      brachial artery in such cases. METHODS: Between July 1992 and 1999, 86 children
      with Grade III supracondylar fracture of humerus were treated at King Khalid
      University Hospital, Riyadh, Kingdom of Saudi Arabia The history, physical
      examination, vascular status of limb before and after close reduction
      percutaneous pinning of fracture were recorded. All children having persistently
      absent radial pulse and monophasic flow doppler signals after close reduction
      percutaneous pinning under went exploration of brachial artery. RESULTS: Of the
      86 children with Grade III supracondylar fracture of humerus, 6 had persistently
      absent radial pulse with monophasic flow doppler signals after close reduction
      percutaneous pinning. Five children had one warm pink well perfused hand and one
      cold pale poorly perfused hand. All 6 under went exploration of brachial artery
      and were found to have entrapped artery at the fracture site. There was an
      immediate return of radial pulse with triphasic Doppler flow on release of
      brachial artery. CONCLUSION: Persistently absent radial pulse with objectivity,
      obtained by doppler ultrasound in the form of absent or monophasic flow in radial
      artery, is a reliable indicator of vascular compromise. Surgical exploration of
      brachial artery by a competent surgeon is to be carried out to avoid early and
      late complication, of pulseless limb in children with displaced supracondylar
      fracture of humerus.

PMID- 11590455
TI  - Blood lipids and body fat in Bahraini women.
AB  - OBJECTIVE: The aim of this study was to examine some biomedical parameters of a
      representative sample from the population of overweight and obese, and average
      weight Bahraini women visiting 2 health centers in Bahrain. METHODS: This study
      was conducted over a period of 4 months in 2 health centers in the urban city of
      Muharraq in Bahrain, namely Muharraq Health Center and Shaikh Salman Health
      Center. The association was examined between body mass index, and the
      distribution of body fat determined by the waist hip ratio. Serum triglycerides,
      total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, as well as glucose levels were measured. RESULTS: The 2 groups of
      pre-menopausal women selected for this study were of similar age (mean of 30.4
      and 30.7 years) but differed significantly in their body mass index values;
      however, their mean waist hip ratio was similar (0.80 and 0.82). The type of
      obesity shown by these Bahraini women was not associated with an elevation of
      serum glucose concentrations, or with significant differences in either serum
      cholesterol or triglyceride concentrations. There was however, a statistically
      significant difference between the 2 groups with respect to the level of high
      density lipoprotein cholesterol, which was lower in the obese group, compared
      with the lean counterparts. Furthermore, the ratio of high-density lipoprotein to
      low-density lipoprotein cholesterol was significantly lower in the obese
      subjects, compared with the controls. CONCLUSION: Obesity in a group of Bahraini
      women was associated with indices predisposing to coronary heart disease, and
      this has public health implications.

PMID- 11590456
TI  - Effect of amiodarone on atrial fibrillation after coronary artery bypass surgery.
AB  - OBJECTIVE: Atrial fibrillation occurs in 10% 40% of patients undergoing coronary
      artery bypass grafting. This study investigates whether prophylactic Amiodarone
      use reduces the rate of atrial fibrillation post myocardial revascularisation.
      METHODS: In a prospective study conducted at the Cardiothoracic Center over a 6
      month period, 192 patients were randomized to either Amiodarone or placebo. The
      Amiodarone group received Amiodarone infusion followed by oral Amiodarone on a
      decreasing dose for a total period of 6 weeks. The placebo group were started on
      an infusion of dextrose 5% solution and then maintained on a matched regimen of
      placebo tablets for a corresponding period of time. RESULTS: Of the 100 patients
      recruited for the Amiodarone arm of the study, 12 were excluded for a variety of
      reasons detailed in the discussion with atrial fibrillation occurring in 28 (a
      rate of 32%). Of the 92 controls, 32 developed atrial fibrillation (a rate of
      35%). There were no significant differences between the groups. The maximum
      ventricular rate during atrial fibrillation however, was significantly slower in
      the Amiodarone group (108+/-18) compared to (136+/-22) P<0.05. Moreover, there
      were no significant differences in the mortality rates between the 2 groups; a
      rate of 3% (3 of 88) in the Amiodarone group as opposed to 3% (3 of 92) in the
      controls. CONCLUSION: In this study prophylactic Amiodarone did not reduce the
      rate of atrial fibrillation post coronary artery bypass surgery. However, it
      reduced the maximum ventricular rate. Amiodarone had no effect on mortality post
      coronary artery bypass.

PMID- 11590457
TI  - Ring chromosome 13 in an Omani infant boy with mental retardation and multiple
      congenital anomalies.
AB  - An Omani infant boy with severe physical and psychomotor retardation, facial
      dysmorphism, and anomalies of the cardiovascular and genito-urinary systems is
      described. The chromosomal analysis revealed a 46, XY, r (13) (p11;q34)
      karyotype. The cytogenetic basis of this rare abnormality is outlined and
      phenotypic features are compared with published reports.

PMID- 11590458
TI  - A case of Turcot's Syndrome in a child with malignant transformation.
AB  - Turcot's syndrome or the glioma polyposis syndrome is a rare variant of the
      polyposis syndrome and it is characterized by colonic polyposis and central
      nervous system neoplasm typically a glioblastoma or a medulloblastoma. We present
      a case of Turcot's syndrome in a child with malignant transformation.

PMID- 11590460
TI  - Paradoxical response to chemotherapy in tuberculous pleural effusion.

PMID- 11590459
TI  - Leukemic synovitis as a presentation of myelomonocytic blast crisis of chronic
      myeloid leukemia.
AB  - We describe a patient with a 2-month history of right shoulder monoarthritis and
      fever as the presenting symptoms of a subsequent diagnosis of chronic myeloid
      leukemia in blast crisis. Imaging studies showed changes consistent with leukemic
      infiltration of the soft tissues around the right shoulder joint and the proximal
      humerus. Immunophenotypic and morphologic analysis of the large number of cells
      obtained from the synovial fluid confirmed the shoulder synovitis to be an
      extramedullary manifestation of myelomonocytic blast crisis of chronic myeloid
      leukemia. The patient was not a candidate for aggressive chemotherapy treatment
      because of her poor overall condition, and she had no compatible donor for
      allogenic bone marrow transplantation. Her painful arthropathy was refractory to
      standard pain management but she achieved excellent pain relief with palliative
      radiation therapy. We conclude that the involvement of extramedullary sites by
      chronic myeloid leukemia blast cells can predate hematological blast crisis in
      some of chronic myeloid leukemia cases. Also, painful leukemic synovitis can be
      managed by low dose radiotherapy in a candidate who is refractory to chemotherapy
      and other medical therapy.

PMID- 11590461
TI  - Organophosphate poisoning in children - atropine, pralidoxime or both?

PMID- 11590462
TI  - An outbreak of methicillin resistant Staphylococcus aureus.

PMID- 11590463
TI  - Pattern of erectile dysfunction in Jeddah City.

PMID- 11590464
TI  - [Sir Nicholas Harold Lloyd Ridley: pioneer of intraocular lens].

PMID- 11590465
TI  - [Postoperative opacification of posterior chamber intraocular lenses - a review].
AB  - Postoperative opacification of intraocular lenses (IOLs) is a very unpleasant
      complication for the ophthalmic surgeon and the patient. We report on our
      experiences with opacification of different foldable IOL designs and rigid poly
      (methyl methacrylate) (PMMA) posterior chamber lenses.1. Snowflake degeneration
      of PMMA IOLs: This condition is an unanticipated and surprising late
      postoperative finding 8 to 15 years after implantation. In our opinion, this
      complication is probably not related to the PMMA biomaterial itself, but rather
      it appears to represent a manufacturing problem that has affected a selected,
      albeit large number of lenses manufactured in the 1980s-mid 1990s.2. Degeneration
      of UV absorber material and calcium deposits within the optic of hydrophilic
      IOLs: Two years postoperatively degenerations of UV absorber material and calcium
      deposits within the optic of single piece hydrophilic acrylic lenses SC60B-OUV
      manufactured by MDR (Medical developmental research Inc. Clearwater FL, USA) can
      occur. Although the precise mechanism is not fully known, it was assumed that
      these opacifications are due to premature aging of the UV blocking agent
      incorporated in the lens biomaterial and calcification.3. Calcification on the
      surface of the Bausch & Lomb Hydroviewtrade mark IOLs: Twelve to 15 months
      postoperatively granular surface calcifications in Hydroviewtrade mark IOLs
      occured. The mechanism is not fully understood. According to Bausch and Lomb
      studies, part of the components of the packaging contained silicone, which may
      have come off the packaging onto the lens optic, where it then appears to be a
      catalyst for calcium precipitation. The manufacturer has correlated a change in
      packaging with the appearance of the opacification. The manufacturer now believes
      that this problem has been solved. However, final verification will require a
      careful 1 - 2 years clinical study.4. Glistenings in the hydrophobic acrylic
      AcrySoftrade mark IOLs: The time frame of glistenings in the AcrySoftrade mark
      IOLs is highly variable. It has been suggested that the occurrence of glistenings
      may be related to variations in the temperature of the lens just prior to and or
      during insertion into the eye. Formation of vacuoles may occur within the
      submersed acrylic polymer when there is a transient increase and then decrease in
      temperature during the surgical procedure. "Glistenings" may then subsequently
      form by ingress of anterior chamber fluid. Contrast sensitivity can been
      decreased in some patients, but clinically significant decrease of visual acuity
      has been rare.

PMID- 11590466
TI  - [Differential diagnosis of visual aura in migraine and epilepsy].
AB  - Visual phenomena like lightnings, disturbed contours of objects, or skotoma, can
      be due to ophthalmological diseases, but can also occur as symptoms generated by
      the central nervous system ("aura") in migraine or epilepsy. A subsequent
      hemicrania is considered as a hallmark of migraine, but in many cases does not
      allow for a certain distinction from postictal headaches in patients with focal
      epilepsy. A detailed analysis of the aura does, however, provide sufficient
      information for classifying the disorder as an aura in migraine or as a simple
      partial epileptic seizure in most cases. The higher degree of differentiation of
      visual phenomena including colour, movement, and complex visual phenomena, is
      characteristic of the activation of neuronal circuits during an epileptic aura.
      The higher speed of transsynaptic propagation of epileptic discharges and
      postictal inactivation causes a more rapid time-course of the epileptic aura as
      compared to a migraine aura resulting from a depolarization spreading by
      diffusion. Clinically, the diagnosis of epilepsy is supported by additional
      positive motor phenomena or by a transition into a complex partial seizure, e. g.
      when epileptic activity spreads into a temporal lobe. Secondarily generalized
      seizures, however, may also occur in patients with migraine. Interictal and ictal
      EEG recordings can be important to prove an epileptic origin, but their
      sensitivity is low if ictal discharges remain limited to a small brain area. In
      rare cases, measurements of ictal cerebral perfusion can contribute to the
      differential diagnosis.

PMID- 11590468
TI  - [First results of implantation of a new, potentially accommodative posterior
      chamber intraocular lens].
AB  - PURPOSE: Conventional posterior chamber intraocular lenses (PCIOL) generally
      provide excellent visual acuity but do not restore accommodation. A new,
      potentially accommodative PCIOL has been designed after principles elaborated by
      K.D. Hanna using finite element models. However, before newly developed PCIOL may
      be implanted routinely in larger numbers of patients, careful and meticulous
      evaluation in clinical studies is necessary. Thus, it was the aim of this study
      to investigate intra- and early 3-month postoperative findings after implantation
      of the newly designed PCIOL. PATIENTS AND METHODS: In a prospective pilot and
      safety study that was approved by the ethics committee of our university, six
      eyes of six patients (2 males, 4 females, age range 54 to 87 years) with senile
      or presenile cataract underwent phacoemulsification and implantation of the new
      PCIOL by one surgeon between June and November 2000. The PCIOL (1 CU, HumanOptics
      AG, Erlangen, Germany) is a one-piece hydrophilic acrylic foldable lens with an
      optic diameter of 5.5 mm. Modified haptics are intended to allow anterior
      movement of the lens optic as a function of contraction of the ciliary muscle.
      Intra- and early postoperative findings obtained after one and two days, one, two
      and six weeks and 3 months postoperatively were documented prospectively.
      Postoperative examinations included recording of distance and near visual acuity
      both obtained with best distance correction, determination of subjective near
      point and measurement of distance and near refraction by streak retinoscopy.
      Follow-up was at least three months in all patients. RESULTS: Surgery was
      uncomplicated in all patients with successful in-the-bag implantation and good
      centration of the PCIOL. The postoperative course was uncomplicated without
      inflammation, hemorrhage, synechiae or decentration. Visual acuity improved in
      all patients according to the status of the macula with values between 20/200
      (atrophic maculopathy) and 20/20. After three to six months we observed a
      difference between retinoscopic near and distance refraction of 0.625 to 1.875 D
      and subjective near points of 40 to 100 cm. Near visual acuity with distance
      correction ranged from 0.1 or J 16 (atrophic maculopathy) to 0.4 or J 7.
      CONCLUSIONS: These early and preliminary results of our small pilot study are
      encouraging. Our findings may indicate at least some degree of pseudophakic
      accommodation. However, further studies with additional methods of measurements,
      with longer follow-up, more patients and controlled studies with control groups
      are essential to further determine safety and potential accommodative power of
      this new PCIOL.

PMID- 11590469
TI  - [Impact of pterygium size on corneal topography and visual acuity - a prospective
      clinical cross-sectional study].
AB  - PURPOSE: Pterygia may cause topographic changes featuring increase of
      astigmatism. The purpose of this study was to quantify the impact of the head
      limbus-distance (=height) and limbal base length of the pterygium on the anterior
      corneal curvature and visual acuity before excision. PATIENTS AND METHODS: In 52
      eyes (19 female, 33 male) with a mean age of 53 +/- 14 years the pterygium size
      (height, base length, area) was quantified using projected preoperative clinical
      slides and was correlated with visual acuity, refractive, keratometric,
      topographic astigmatism and Surface Regularity Index (SRI), Surface Asymmetry
      Index (SAI) of the TMS-1 videokeratoscope. RESULTS: The mean height of the
      pterygium was 3.1 +/- 1.4 (0.8 to 6.7) mm, the mean base length was 5.1 +/- 1.4
      (2.9 to 7.8) mm, the estimated mean area was 11.4 +/- 6.9 (2.1 to 29.4) mm(2).
      The increasing pterygium height and area resulted in a highly significant
      elevation of the preoperative SRI and SAI values (p </= 0.01). The amount of
      keratometric (p=0.02) and topographic astigmatism (p=0.001) correlated
      significantly with height and area of the pterygium. In addition, pterygium size
      correlated significantly with the differences of zonal corneal power between
      steepest and flattest hemimeridian in the 3-mm zone or 5-mm zone, respectively (p
      </= 0.01). Best-corrected visual acuity and height/area of the pterygium
      correlated significantly inversely (p=0.001). Visual acuity seemed to be mostly
      unaffected up to a height of 2.5 mm. Overall, the impact of the base length was
      much less striking. Topographic astigmatism (3.3 +/- 2.8 D) was significantly
      larger than keratometric astigmatism (2.1 +/- 2.1 D) (p=0.001). The larger the
      pterygium, the larger was the difference between keratometric astigmatism and
      subjectively tolerated spectacle cylinder (p </= 0.01). CONCLUSIONS: Increasing
      distance of the pterygium head from the limbus results in increased amount and
      irregularity of preoperatively induced corneal astigmatism. This may explain the
      patient's decrease in visual acuity before the pterygium reaches the optical
      axis. Our data may help to determine the adequate time point for primary
      pterygium excision.

PMID- 11590470
TI  - [Measurement of the diameter of segments of retinal branch vessels in digital
      fundus images - An experimental study of the method and reproducibility].
AB  - PURPOSE: The aim of this study was the evaluation of new algorithms to measure
      diameter of segments of retinal branch vessels offline in local dependence and
      independent by observer. Methods 360 flashed fundus images (camera FF 450 ZEISS
      Germany, Visualis IMEDOS GmbH Weimar/Germany) of 12 eyes of healthy volunteers
      (10 independent sessions containing 3 images for every eye) were analysed.
      Algorithms detect the vessel diameter along the vessel course automatically.
      Corresponding segments of a retinal artery and vein were examined (mean length of
      the segment 2.5 mm) in every image of one eye. Results The marked arterial
      segment was detected automatically in 359 pictures and the venous segment in all
      pictures. The mean vessel diameter was detected in single pictures with a mean
      coefficient of variation (CV) for arteries of 3.4 % and for veins of 2.7 %. The
      differences of arterial and venous diameter between images were not significant.
      Analyzing sessions the CV of the mean vessel diameter were reduced for arteries
      to 2.7 % and for veins to 2.5 %. The standard deviation of the mean vessel
      diameter was independent of the vessel diameter (branch vessels with diameter of
      120 to 200 micrometer). The mean CV of the vessel diameter at single locations
      were 5.7 % for arteries and 3.8 % for veins. Conclusions The new algorithms are
      useful for retinal vessel analysis, if there are no questions concerning the
      dynamic of vessel behaviour.

PMID- 11590471
TI  - [Primary open angle glaucoma in cornea plana masked by false normal applanation
      tonometry (Goldman) - a case report].
AB  - BACKGROUND: Cornea plana is a rare syndrome, which leads to a flat corneal
      curvature due to a reduced sclero-corneal angle. Depending on the regularity of
      the corneal astigmatism the frequently resulting hyperopia may be difficult to
      compensate for. Because of the flatness of the cornea the anterior chamber is
      also flat, the anterior chamber angle can be restricted, and the applanatory
      intraocular pressures (IOPs) are measured too low. A primary open angle glaucoma
      is therefore not diagnosed for a long time, until changes of the optic nerve head
      occur. Patient and methods We report on a 66-year-old male with cornea plana.
      Although his intraocular pressure (IOP), measured with an applanation tonometer
      (Goldmann), had always been normal (< 21 mm Hg), he suffered from an increasing
      glaucomatous atrophy of the optic disc. We carried out a complete
      ophthalmological investigation, including keratometry and corneal topography
      analysis (TMS-1, Tomey). Furthermore, visual field was determined (G1, Octopus)
      and the optic nerve heads were documented and analysed by papillometry. A 48-hour
      tension profile was worked out for both eyes including applanation and Schiotz
      tonometry. Results The central refractive power of the cornea was 31 diopters and
      the cornea seemed to be flattened on slit lamp evaluation. The glaucomatous
      atrophy of the optic disc was more pronounced in the OD than in the OS
      (OD=neuroretinal rim loss in the upper part, at the bottom and in the lateral
      part of the optic disc, OS=laterally distinct neuroretinal rim loss). While the
      anterior parts of the eye were shortened (depth of the anterior chamber was
      OD/OS=1.9 mm), a macrophthalmus posterior was stated (axial length OD=25.78 mm,
      OS=25.72 mm). However, the IOPs were measured below 21 mm Hg by applanation
      during the entire tension analysis, comparable values measured with the Schiotz
      tonometer showed values above 21 mm Hg. We converted the applanatory IOP values
      according to the flat corneal power, as described in literature (addition of 1 mm
      Hg to the applanatory values per 3 diopters decreased corneal power). The tension
      analysis now showed increased values, as expected after observation of the
      glaucomatous excavated optic nerve head. Conclusion In patients with cornea plana
      applanatory IOPs are measured too low. Therefore in case of very flat corneas a
      mathematical correction of the applanatory IOP should be carried out, in order to
      diagnose a primary open angle glaucoma early enough.

PMID- 11590472
TI  - [Malignant transformation of a choroidal nevus 6 years after brachytherapy of a
      non-contiguous choroidal melanoma - a case report and review of literature].
AB  - BACKGROUND: Brachytherapy is a well established procedure for treatment of
      malignant choroidal processes. Approximately 5 % of the cases, will show local
      recurrences within 6 years. We report a patient who has developed a malignant
      transformation of an uveal nevus following brachytherapy of a non-contiguous
      uveal melanoma. In addition, we reviewed the literature concerning similar cases.
      HISTORY AND SIGNS: In 1991 a Ruthenium application was performed on a 65-year old
      patient suffering of an equatorial malignant choroidal melanoma. At that time, a
      nevus at the posterior pole was present. From 1997 to 1998 the nevus continuously
      increased in size. Visual acuity decreased and a retinal detachment developed.
      Combining the clinical and the sonographic findings, the diagnosis of a malignant
      melanoma arising of a nevus was established. Enucleation was performed in 1998.
      THERAPY AND OUTCOME: Histologic examination revealed the diagnosis of an
      epithelioid-cell-type malignant uveal melanoma arising in a nevus. Till now, the
      patient is free of metastatic disease. CONCLUSION: Non-contiguous development of
      uveal melanomas in the same eye are extremely rare. We could identify in the
      literature 5 cases of non-contiguous melanomas following brachytherapy of an
      uveal melanoma. In none of these cases, the secondary melanoma has arisen in a
      nevus. Follow-up examination of patients with uveal melanoma treated with
      brachytherapy should include not only examination of the treated area, but also
      the whole fundus of the eye in order to recognize secondary tumours as early as
      possible.

PMID- 11590473
TI  - [Diffuse melanocytic nevus of the iris and absolute glaucoma].
AB  - BACKGROUND: Ferry et al. (8) showed that 35 % of eyes which have been enucleated
      because of a clinically suspected malignant iris lesion did not reveal a
      histologically malignant iris tumor. PATIENT: A 43-year old male presented with a
      blind, painful left eye, which has developed over a time period of 6 months.
      Ophthalmologic examination revealed the presence of pigmented iris stromal
      lesions associated with diffuse pigmentation of the chamber angle and the
      development of absolute glaucoma. A diffuse iridociliary malignant melanoma (ring
      melanoma) was suspected and the blind painful eye was enucleated. Histologic
      examination revealed the presence of a benign melanocytic lesion, i.e. a spindle
      cell nevus of the iris with surface plaques causing diffuse extension of the
      chamber angle, trabecular meshwork, Schlemm's canal, and the ciliary body.
      CONCLUSION: The malignant potential of iris lesions may be difficult to assess on
      clinical grounds only. Histologically, benign melanocytic proliferation may cause
      diffuse extension into the ciliary body as well as the chamber angle leading to
      an increase in intraocular pressure. In order to reach a final diagnosis a biopsy
      of the lesion is necessary.

PMID- 11590474
TI  - Physiology and pathophysiology of the serotonergic system and its implications on
      mental and physical performance. Part I.
AB  - Serotonin (5-HT), one of the evolutionary oldest central neurotransmitters,
      regulates the most extensive modulatory behavioral system in the brain of
      vertebrates. 5-HT projections are influenced by extrinsic and intrinsic impulses
      from different cortical brain areas, which reach Raphe nuclei over feedback
      loops, containing external and internal body information about planning,
      evaluation, motivation or excitation. Serotonergic neurotransmission adjusts
      neuromodulation with consecutive adequate stimulation of the neuronal network.
      This depends on appropriate equilibration of presynaptic 5-HT storage and release
      but also on 5-HT reuptake from synaptic cleft by 5-HT transporters. The
      associated pre and postsynaptic 5-HT receptor cooperation, postsynaptic second
      messenger response and phosphoinositide signaling mediated by postsynaptic 5
      HT(2) receptor subpopulation alter signal transduction in which myristolated
      alanine rich C kinase substrate is prominently involved in regulation of further
      central 5-HT areas in the brain and corresponding functional neuronal changes.
      Even though the central function of 5-HT neurotransmission is dominating in the
      multifold behavioral regulation, peripheral concentration of tryptophan (TRP)
      adjusted by hepatic and non-hepatic TRP pyrrolase, TRP liberation from albumin
      especially by adrenergic stimulation of free fatty acids, TRP passage across the
      blood-brain barrier and TRP hydroxylase activity are also important for
      appropriate 5-HT neurotransmission as they affect central 5-HT synthesis. The
      high adaptability of 5-HT neurotransmission is able to compensate neuromodular
      dysfunctions in the brain by mechanisms which mediate 5-HT biosynthesis, release,
      reuptake, pre and postsynaptic receptor stimulation with the respective second
      messenger response and signal transduction to various areas of the brain which
      are involved in regulation of behavior, mood, memory, learning and attenuation of
      obsession, depending on the different vigilance states of the subject. Adequate 5
      HT system function supports regulation of intercommunicative neuronal
      transmission in the brain, which optimizes behavioral neuromodulation during and
      after transient disturbances of neuromodular behavior caused by stress-induced
      exertions, but also in permanent disorder such as major depression. Serotonergic
      neurotransmission improves the clinical course due to compensatory 5-HT impulse
      correction. This hypothetical interpretation of the serotonergic central
      neuromodular regulation and interaction with the neuronal network is supported by
      findings both in functional disturbances and persistent impairments in mental
      disorders. A comparison of the symptomatology in permanent and transient
      disturbance of brain neuromodulation enhances our basic knowledge on the
      regulative factors e. g. in endogenous depression and depressive behavioral
      changes after exhaustive exercise. This consideration exhibits that the
      interaction between altered central neuromodulation and peripheral metabolic and
      hormonal dysfunctions is able to differentiate the etiology of the symptoms. It
      is suggested that the central neuromodular disturbance of stress-induced causes
      might initiate the manifestation of the impairment. The theoretical background of
      this hypothesis is discussed in the present review.

PMID- 11590475
TI  - Physiology and pathophysiology of the serotonergic system and its implications on
      mental and physical performance. Part II.
AB  - As shown in the first part of this review, well equilibrated neurotransmission in
      which 5-HT plays a dominant role is important for proper neuromodulation and
      adjustment of neuronal network elements. Adequate 5-HT system function supports
      regulation of intercommunicative neuronal transmission in the brain, which
      optimizes behavioral neuromodulation during and after different forms of
      exertions, thereby preventing transient dysregulation. Impairment of
      neuromodulation and neuronal network in the brain with transient dysfunctions or
      permanent substantial deficits at manifestation of various types of depression
      results from prevalent impairment of 5-HT neurotransmission and its central
      interaction with other neurotransmitter systems. Exercise-induced increase of
      free tryptophan (TRP) in blood occurs due to liberation from albumin, which is
      caused by adrenergically induced lipolysis of free fatty acids and results in
      higher free TRP uptake into the brain. Consecutively enhanced serotonin (5-HT)
      biosynthesis does not per se initiate mood impairment or central fatigue. It is
      suggested that in overtrained athletes central fatigue, mental deficiency and
      behavioral alterations with depressive mood are probably not primarily caused by
      metabolic and neuromuscular alterations. The primary trigger of these transient
      behavioural alterations might instead be initiated by a central exhaustive
      exercise stress which elicits impairment of complex neuromodulation, also
      afflicting the interaction of central neurotransmitters or hypothalamic
      neuropeptides and releasing factors. In a consecutive correction of the
      variation, the implication of the serotonergic system on the central neuromodular
      disturbance might improve or prevent the progressive course both in transient and
      in permanent mental disorders. However, an unsuccessful attempt to improve the
      depressive symptomatology leads mostly to an overproportional exaggeration of the
      behavioral changes.

PMID- 11590476
TI  - Pulmonary function subsequent to expiratory muscle fatigue in healthy humans.
AB  - One of the mechanisms proposed to explain the decrement in pulmonary function
      often seen after exercise is fatigue of the expiratory muscles. To test the
      hypothesis that expiratory muscle fatigue alters lung function, several indices
      of pulmonary function were measured before and after expiratory muscle fatigue
      was induced by expiratory loaded breathing. Eight subjects completed a fatigue
      trial (EF) in which expiratory threshold loaded breathing was performed at an
      initial resistance equal to 80 % of their maximal expiratory pressure (MEP), at a
      respiratory rate of 13 bpm, and a duty cycle (T(I)/T(Tot)) of 0.33. MEP was taken
      at predefined intervals throughout the loaded breathing protocol, and loaded
      breathing was discontinued when MEP was less than 80 % of each subject's pre EF
      trial MEP (T(Lim)). FVC, FEV(1.0), FEF(25 %), FEF(25-75 %), and maximal
      inspiratory and expiratory pressures (MIP and MEP) were taken prior to,
      immediately after, and at 5, 10, and 15 min post fatigue. On a separate day a
      control trial (CON) was performed that was identical to each subjects EF trial
      with the exception that no expiratory load was utilized. At T(Lim) MEP was
      significantly reduced (p < 0.001) by 23.5 % from the pre-expiratory loaded
      breathing value (183.1 +/- 39.56 to 140.13 +/- 30.45 mmHg), whereas it remained
      unchanged during the CON trial (191.06 +/- 44.18 to 188.06 +/- 43.50 mmHg). FVC
      measured prior to and immediately after T(Lim) remained unchanged following both
      the EF (5349.45 +/- 1130.8 to 5387.43 +/- 1139.92 mL) and CON trials (5287.75 +/-
      1220.29 and 5352.78 +/- 1191.30 mL). These results suggest that any expiratory
      muscle fatigue developed during exercise by itself does not result in altered
      pulmonary function. However, any interactions between expiratory muscle fatigue
      and other consequences of exercise that may alter lung function cannot be ruled
      out.

PMID- 11590477
TI  - Blood volume and hemoglobin mass in elite athletes of different disciplines.
AB  - Although it is well known that athletes have considerably larger blood volumes
      than untrained individuals, there is no data available describing the blood
      volume variability among differently trained athletes. The first aim of the study
      was to determine whether athletes from different disciplines are characterized by
      different blood volumes and secondly to what extent the blood volume can possibly
      limit endurance performance within a particular discipline. We investigated 94
      male elite athletes subdivided into the following 6 groups: downhill skiing
      (DHS), swimming (S), running (R), triathlon (TA), cycling junior (CJ) and cycling
      professional (CP). Two groups of untrained subjects (UT) and leisure sportsmen
      (LS) served as controls. Total hemoglobin (tHb) and blood volume (BV) were
      measured by the CO-rebreathing method. In comparison to UT (mean +/- SD: tHb 11.0
      +/- 1.1 g/kg, BV 78.3 +/- 7.9 ml/kg) tHb and BV were about 35 - 40 % higher in
      the endurance groups R, TA, CJ, and CP (e. g. in CP: tHb 15.3 +/- 1.3 g/kg, BV
      107.1 +/- 7.0 ml/kg). Within the endurance groups we found no significant
      differences. The anaerobic discipline DHS was characterized by very low BV (87.6
      +/- 3.1 ml/kg). S had an intermediate position (BV 97.4 +/- 6.1 ml/kg), probably
      because of the immersion effects during training in the water. VO(2)max was
      significantly related to tHb and BV not only in the whole group but also in all
      endurance disciplines. The reasons for the different BVs are an increased
      adaptation to training stimuli and probably also individual predisposing genetic
      factors.

PMID- 11590478
TI  - Does endurance or sprint training influence the perception of the optimal
      pedalling rate during submaximal cycling exercise?
AB  - The purpose of this study was to investigate the effects of endurance and sprint
      training on the perception of the optimal pedalling rate during a submaximal
      cycling exercise. Six subjects specialized in endurance activities and 6 subjects
      trained in sprinting activities used the model of bicycling at various pedalling
      rates with the same power output (150W) on a cycle ergometer. Individual 2nd
      order polynomial relationships were determined between oxygen consumption (VO(2))
      and velocity and between rate of perceived exertion (RPE) and velocity. Optimal
      velocity, with respect to minimum of VO(2) (OV(VO2)) and to minimum of RPE
      (OV(RPE)), were calculated for all subjects, respectively. The close similarity
      found between the VO(2)-velocity and the RPE-velocity curves confirmed that the
      overall RPE was mainly influenced by the central factor. As OV(RPE) and OV(VO2)
      were not significantly correlated and as OV(RPE) was significantly higher than
      OV(VO2), other factors than central may also have influenced the RPE. The
      significant higher OV(RPE) values (p<0.05) observed in the sprint vs. endurance
      groups suggested that different training background may have influenced the RPE.
      These differences could also be explained by a significantly higher OV(VO2) in
      sprint than in endurance groups, the subjects being sensitive to the pedalling
      rate for which the energy expenditure is minimal.

PMID- 11590479
TI  - Specific and transfer effects induced by arm or leg training.
AB  - The purpose of the present study was to examine both the specific and the
      transfer effects of a Square Wave Endurance Exercise Test (SWEET) and to
      investigate the determining factors of transfer effect. A control group (CG, n =
      5) and 2 experimental groups were studied. Experimental groups completed 3
      days/week a 45 min SWEET over 6 weeks, either with the arms using a wheelchair
      ergometer (AG, n = 5) or with the legs using a cycling ergometer (LG, n = 5). All
      subjects performed before and after training two maximal progressive tests: the
      first one with the arms and the second with the legs. During those tests oxygen
      uptake (VO(2)) and cardiorespiratory parameters were continuously measured.
      Specific effects (changes between the tests performed with trained limbs) were
      observed: the peak power output (W(p)) and VO(2) were significantly increased by
      both arm (+ 66 %, + 35 %) and leg (+ 17 %, + 14 %) training. At ventilatory
      threshold (VT), power output (W) and VO(2) were significantly increased with arm
      (+ 145 % and + 51 %) and leg (+ 53 % and + 46 %) training. Transfer effects
      (changes between pre and post tests performed with untrained limbs) were
      observed: W(p) and VO(2) were not increased in AG while W(p) was increased in LG
      (+ 11 %). At VT, W and VO(2) were increased with arm (+ 19 % and + 23 %) and leg
      (+ 33 % and + 46 %) training. For AG and LG the VO(2) expressed in percent of the
      VO(2) peak was increased (+ 19 % and + 33 %, respectively) and the O(2p) was also
      increased (+ 30 %) for LG. These results show that SWEET training induced
      specific and transfer effects. Moreover, the initial level of the subjects, the
      type and the intensity of the training seem to be the major factors for effective
      observable transfer effects.

PMID- 11590480
TI  - Evaluation of the Accusport lactate analyser.
AB  - It has been suggested that lactate concentrations may provide a guide to an
      optimal training intensity. However, lactate concentrations established during
      incremental exercise in the laboratory are not always indicative of what is
      occurring during constant-load exercise at the same intensity. Ideally, lactate
      concentrations should be measured during a training session and immediately
      reported to the athlete to ensure that the athlete is working at the desired
      intensity. The purpose of this investigation was, therefore, to determine the
      reliability and validity of a compact, portable lactate analyser (ACCUSPORT;
      Boeringer Mannheim, Castle Hill, Australia). A total of 224 capillary blood
      samples were taken from athletes who took part in routine laboratory testing.
      Seventy-three of these capillary blood samples were analysed in duplicate with
      the Accusport for determination of intraclass, single-trial reliability. Day-to
      day intraclass reliability of the Accusport was assessed by analyzing known
      concentrations of aqueous lactate solutions on seven consecutive days. The
      validity of the Accusport analyser was assessed by comparing the 224 capillary
      blood lactate concentrations determined on the Accusport with the lactate
      concentration obtained using a MICRO STAT LM3 (Analox Instruments Ltd., London,
      UK). In addition, lactate parameters derived from the lactate concentrations
      obtained with the two analysers were compared. The Accusport showed high single
      trial intraclass reliability (R = 0.992; Standard Error of Measurement [SE(M)] =
      0.3 mmol x l(-1); n = 73) and high day-to-day intraclass reliability (R = 0.993;
      SE(M) = 0.4 mmol x l(-1); n = 42). Despite a strong correlation between blood
      lactate concentrations obtained on the two analysers (r = 0.96; n = 224) the
      limits of agreement were + 1.9 to - 2.2 mmol x l(-1). Although the mean values
      for power output, HR and lactate concentration associated with the lactate
      parameters were not significantly different when determined on the Accusport or
      Micro Stat, some individuals did record large differences between analysis
      methods. In summary, the results of this investigation have shown that lactate
      concentrations can be reliably determined within a single trial and from day-to
      day using the Accusport analyser. However, for some athletes, it is not valid to
      compare lactate concentrations or lactate parameters determined on the Accusport
      with those determined using the Micro Stat LM3 lactate analyser.

PMID- 11590481
TI  - Sports injuries in floorball: a prospective one-year follow-up study.
AB  - Two hundred and ninety-five licensed floorball players from Finnish premier to
      fifth division were observed prospectively for one season to study the incidence,
      nature, causes and severity of floorball injuries. During the study period, 100
      out of the 295 (34 %) players sustained 120 injuries. Thirty-seven percent
      (73/199) of the male players and 28 % (27/96) of the females suffered from an
      injury. The injury rate was 1.0 per 1000 practice hours for both sexes. The
      injury rates per 1000 game hours were 23.7 for men and 15.9 for women. One
      hundred injuries (83 %) were acute and the remaining 20 (17 %) were overuse
      injuries. Sprain was the most common type of injury in men while overuse injuries
      were the most frequent injury type in women. The lower extremity was involved in
      62 %, spine or trunk in 19 % and upper extremity in 10 % of the injuries. The
      most commonly injured sites were the knee and ankle (22 % and 20 % of all
      injuries), followed by head and neck (8 %). In both sexes the majority of
      injuries were minor, level II, injuries. Ten of the knee injuries (38 %) were
      serious, level IV injuries, of which seven were ACL ruptures. In conclusion, the
      individual risk of injury in floorball is relatively low in game practice while
      rather high during the game itself. Before initiation of clinical trials on
      prevention of floorball injuries, an exact knowledge of the risk factors and
      mechanisms of floorball injuries are needed.

PMID- 11590482
TI  - Vitamin C supplementation attenuates the increases in circulating cortisol,
      adrenaline and anti-inflammatory polypeptides following ultramarathon running.
AB  - The effects of vitamin C supplementation on the alterations in the circulating
      concentrations of cortisol, adrenaline, interleukin-10 (IL-10) and interleukin-1
      receptor antagonist (IL-1Ra) which accompany ultramarathon running were measured
      using immuno-chemiluminescence, radioimmunoassay and ELISA procedures. Forty-five
      participants in the 1999 Comrades 90 km marathon were divided into equal groups
      (n = 15) receiving 500 mg/day Vit C (VC-500), 1500 mg/day Vit C (VC-1500) or
      placebo (P) for 7 days before the race, on the day of the race, and for 2 days
      following completion. Runners recorded dietary intake before, during and after
      the race and provided 35 ml blood samples 15 - 18 hrs before the race,
      immediately post-race, 24 hrs post race and 48 hrs post-race. Twenty-nine runners
      (VC-1500, n = 12; VC-500, n = 10; P, n = 7) complied with all study requirements.
      All post-race concentrations were adjusted for plasma volume changes. Analyses of
      dietary intakes and blood glucose and anti-oxidant status on the day preceding
      the race and the day of the race did not reveal that carbohydrate intake or
      plasma vitamins E and A were significant confounders in the study. Mean pre-race
      concentrations of serum vitamin C in VC-500 and VC-1500 groups (128 +/- 31 and
      153 +/- 34 micromol/l) were significantly higher than in the P group (83 +/- 39
      micromol/l). Immediate post-race serum cortisol was significantly lower in the VC
      1500 group (p < 0.05) than in P and VC-500 groups. When the data from VC-500 and
      P groups was combined (n = 17), immediate post-race plasma adrenaline, IL-10 and
      IL-1Ra concentrations were also significantly lower (p < 0.05) in the VC-1500
      group. The study demonstrates an attenuation, albeit transient, of both the
      adrenal stress hormone and anti-inflammatory polypeptide response to prolonged
      exercise in runners who supplemented with 1500 mg vitamin C per day when compared
      to < or = 500 mg per day.

PMID- 11590483
TI  - Clinical utility of monitoring serum cryptococcal antigen (sCRAG) titers in
      patients with AIDS-related cryptococcal disease.
AB  - PURPOSE: The purpose of our study was to define the time course and clinical role
      of monitoring serum cryptococcal antigen titers (sCRAG) in patients with AIDS
      related cryptococcal disease. METHOD: A retrospective chart review was conducted.
      The medical records for all HIV-infected patients with positive cryptococcal
      antigen (CRAG) tests from January 1993 to May 1998 at San Francisco General
      Hospital (SFGH) were reviewed for sCRAG titer levels and clinical outcomes.
      RESULTS: Out of the 314 patients found to have positive antigen tests, 136 met
      the inclusion criteria. Twelve (8.8%) had no change in titer from baseline, 6
      (4.4%) had an increase, and 118 (86.8%) had a decrease. Examining the association
      of sCRAG with time to relapse using a variety of Cox models produced largely null
      results. Rate of change in sCRAG over time (slope) was not significantly
      predictive of time to relapse nor of time to definite relapse/probable
      relapse/persistent disease. CONCLUSION: Although in the majority of patients, the
      sCRAG titers appeared to decrease over time, we could not detect a significant
      correlation between sCRAG titer results of patients who had a clinical response
      to treatment and sCRAG titers in patients who experienced persistent disease,
      probable relapse, or definitive relapse of cryptococcal disease. We conclude that
      follow-up monitoring of the sCRAG titer is not useful in the management of
      patients with AIDS-related cryptococcal disease on treatment.

PMID- 11590484
TI  - Efficacy of a nelfinavir- and nevirapine-containing salvage regimen.
AB  - PURPOSE: In this study, our purpose was to assess the efficacy of nelfinavir- and
      nevirapine-containing salvage regimens in nonnucleoside reverse transcriptase
      inhibitor (NNRTI)-naive patients virologically failing a protease inhibitor (PI)
      based combination. METHOD: A retrospective case note review of all patients
      virologically failing their PI-based combination who were switched to a regimen
      containing both nelfinavir (1 g t.d.s.) and nevirapine (200 mg b.d.). CD4 cell
      counts and viral loads were monitored. Genotypic analysis was performed using RT
      PCR sequencing. RESULTS: Nineteen patients commenced a salvage regimen containing
      nelfinavir and nevirapine. Five patients also changed at least one nucleoside
      reverse transcriptase inhibitor (NRTI), although in one case this represented
      recycling. Thirty-eight percent (6/16) of patients achieved a viral load below
      the level of detection (BLD; <200 copies/mL; complete responders [CR]), 3
      achieved <20 copies/mL. Five patients achieved > or =1 log drop (partial
      responders [PR]) that was not sustained over follow-up, and five failed to
      respond to therapy (nonresponders [NR]). CRs tended to have wild-type NNRTI and
      PI sequences relative to PRs and NRs. CONCLUSION: In heavily pretreated patients,
      a nelfinavir-and nevirapine-containing salvage regimen resulted in a virological
      response in 38% of patients that was sustained in 31% over 63 weeks.

PMID- 11590485
TI  - A clinical study of the combination of 100 mg ritonavir plus 800 mg indinavir as
      salvage therapy: influence of increased plasma drug levels in the rate of
      response.
AB  - PURPOSE: The purpose of our study was to evaluate the efficacy of indinavir (IDV)
      in a twice daily dosing regimen with coadministration of 100 mg ritonavir (RTV)
      and to explore the influence of plasma drug levels in the rate of virologic
      response. METHOD: We performed a prospective study of 59 patients who switched to
      a salvage regimen with two nucleoside analogs plus the combination of 100 mg RTV
      plus 800 mg IDV twice daily. Pharmacokinetics of IDV and RTV were assessed in 11
      patients. RESULTS: Previous antiretroviral exposure was 44 months, and 78% and
      39% of patients had previously failed regimens with either IDV or RTV. Median CD4
      count was 248 x 10(6)/L and HIV load was 3.9 log(10) copies/mL. The median number
      of mutations in the protease gene was 9 (3-14), predominantly at residues 82
      (53%), 90 (42%), and 46 (32%). After 24 weeks, 61% of patients had a viral load
      decrease greater than 1 log(10), and 38% had a viral load below 50 copies/mL.
      Nephrolitiasis, hematuria, or flank pain was observed in 13 patients (22%),
      leading to withdrawal in six cases (10%). IDV trough levels were well above the
      IC(95) (median 1.75 mg/L, interquartile range 1.07-2.57), but RTV trough levels
      were below the IC(95) in 88% of patients. There was a close correlation between
      higher peak levels of IDV, virological response, and renal toxicity. CONCLUSION:
      RTV/IDV 100/800 mg in a twice daily dosing regimen is associated with a
      significant virological response in patients with antiretroviral treatment
      failure. The correlation between plasma drug levels, toxicity, and response
      suggests the usefulness of individualized drug monitoring.

PMID- 11590486
TI  - Effect of the serotonin receptor agonist, buspirone, on immune function in HIV
      infected individuals: a six-month randomized, double-blind, placebo-controlled
      trial.
AB  - PURPOSE: Previous studies have shown that agents modulating the cAMP/PKA pathway
      have a beneficial effect on immune reconstitution in HIV-infected individuals.
      Here we evaluate the effect of buspirone on immune function as measured by CD4
      and CD8 T-cell counts, CD4/CD8 T-cell ratio, HIV viral load, and response to
      pokeweed mitogen (PWM) in antiretroviral naive HIV-1-infected individuals.
      METHOD: Twenty-three HIV-infected patients with CD4 T-cell counts above 300 per
      microL were enrolled in a 6-month double-blinded placebo controlled trial. No
      patients received antiretroviral therapy during the study. Blood samples were
      drawn prior to treatment, after 1 week, 1 month, 3 months, and 6 months, and as a
      follow-up sample 1 month after completion of study. RESULTS: A significant
      decrease in CD8+ T-cell counts (p =.02) and an increase in CD4/CD8 ratio (p
      =.0003) in buspirone-treated patients compared to placebo-treated patients was
      observed. There were no significant differences in CD4 T-cell counts, HIV viral
      load, or proliferative response to PWM between those receiving placebo and those
      receiving buspirone. CONCLUSION: Buspirone treatment leads to significant changes
      in CD8 T-cell count and in CD4/CD8 ratio. Thus, agents affecting the adenosine
      3', 5'-cyclic monophosphate/protein kinase A type 1 (cAMP/PKA-1) pathway may be
      candidates for positive immune modulation in patients with HIV-1 infection.

PMID- 11590487
TI  - The cost-effectiveness of triple nucleoside analogue therapy antiretroviral
      regimens in the treatment of HIV in the United Kingdom.
AB  - PURPOSE: Treatment of HIV infection has improved markedly in recent years due to
      the use of combination antiretroviral therapies. However, the cost of these
      treatments remains a concern for those who fund health services. This article
      reports the results of an economic evaluation to determine the incremental cost
      effectiveness of triple combination nucleoside analogue (NA) therapy compared
      with dual NA therapy. METHOD: A Markov model was developed to assess the
      incremental cost effectiveness of triple therapy treatment versus dual therapy
      treatment. Clinical data was derived from published clinical trials and large
      observational cohorts whilst cost data was derived from a prospective database
      that monitors health care resource use in the UK HIV population. RESULTS: The
      model predicted that triple NA combination treatment extended life expectancy by
      an additional 1.2 years compared with dual therapy NA treatment with an
      incremental cost-effectiveness ratio of 8,419 pounds per life-year saved. The
      incremental cost per quality-adjusted life-year (QALY) was estimated to be
      between 10,072-16,168 pounds per QALY gained depending on the assumptions.
      CONCLUSION: The results show triple nucleoside analogue therapy to be a cost
      effective means of delaying HIV progression and extending life expectancy.
      However, further research into this issue is warranted.

PMID- 11590488
TI  - Measuring adherence to antiretroviral medications in clinical trials.
AB  - Antiretroviral medications have the potential to transform HIV infection from a
      fatal to a chronic disease. One of the significant barriers to clinical success
      is medication nonadherence. Measuring adherence in clinical trials is
      increasingly important because inadequate adherence may explain some of the
      variation in clinical response in antiretroviral clinical trials. Additionally,
      to quantitate the success of interventions that improve adherence, accurate
      measures need to be utilized. This article summarizes commonly used adherence
      measures in HIV clinical trials and observational studies such as patient self
      report, pill counts, plasma levels, and electronic monitoring. The merits and
      shortcomings of each measure are discussed.

PMID- 11590489
TI  - Therapeutic options for the management of oropharyngeal and esophageal
      candidiasis in HIV/AIDS patients.
AB  - Mucocutaneous candidiasis is frequently one of the first signs of HIV infection.
      Over 90% of patients with AIDS will develop oropharyngeal candidiasis at some
      time during their illness. Although numerous antifungal agents are available,
      azoles, both topical (clotrimazole) and systemic (fluconazole, itraconazole),
      have replaced older topical antifungals (gentian violet and nystatin) in the
      management of oropharyngeal candidiasis in these patients. The systemic azoles,
      itraconazole and fluconazole, are generally safe and effective agents in HIV
      infected patients with oropharyngeal candidiasis. A concern in these patients is
      clinical relapse, which appears to be dependent on degree of immunosuppression
      and is more common following clotrimazole and ketoconazole than following
      fluconazole or itraconazole. Candida esophagitis is also of concern, since it
      occurs in more than 10% of patients with AIDS. Fluconazole is an integral part of
      the management of mucosal candidiasis. A cyclodextrin oral solution formulation
      of itraconazole has clinical response rates similar to fluconazole and is an
      effective alternative. In patients with fluconazole-refractory mucosal
      candidiasis, treatment options include itraconazole, amphotericin B oral
      suspension, and parenteral amphotericin B.

PMID- 11590490
TI  - Guidelines for the use of antiretroviral agents in HIV-infected adults and
      adolescents, January 28, 2000 by the Panel on Clinical Practices for Treatment of
      HIV Infection.

PMID- 11590491
TI  - Selected topics from the Seventh Conference on Retroviruses and Opportunistic
      Infections, January 30 - February 2, 2000. San Francisco, California.

PMID- 11590492
TI  - Combination therapy with hydroxyurea versus without hydroxyurea as first line
      treatment options for antiretroviral-naive patients.
AB  - PURPOSE: This study analyzed whether combination therapy with hydroxyurea (HU)
      could be considered as first line treatment for antiretroviral-naive patients.
      METHOD: The prospective open-label study was carried out from March 1996 to May
      2000. The antiretroviral treatments were treatment 1-didanosine 400 mg/day,
      stavudine 60/80 mg/day, and HU 500 mg/day; treatment 2-two nucleosides plus a
      protease inhibitor; treatment 3-didanosine, indinavir, and HU (500-1,000 mg/day).
      The viral load (VL) and CD4 determinations were performed at weeks 24, 48, 72,
      and 96. RESULTS: The sample comprised 284 patients. The distribution of patients
      by levels of VL and CD4 were similar in the three treatment groups. At week 24,
      patients receiving T1 and T3 achieved higher percentages of undetectable VL (89%
      and 81%, respectively) with no significant differences (p =.127) between them.
      The T2 group showed a lower proportion (58%) of undetectable VL, which was
      significantly lower than T1 (p <.0001) and T3 (p <.0007). At week 48, the results
      were similar to week 24. At week 96, nearly all patients had undetectable viral
      load (UVL). The analysis of adverse effects showed that the T2 group at week 48
      had a greater proportion of adverse effects that was significantly different from
      T1 (p =.0026); T3 had intermediate values with no significant difference from T2
      (p =.45) and from T1 (p =.048). At week 48, T1 showed higher adherence level with
      significant difference from the other two treatments. CONCLUSION: Patients were
      followed for some 96 weeks and, with an intention-to-treat analysis, were found
      to do better virologically and Clinically in treatment groups containing HU. The
      combination of antiretroviral drugs with HU may be an excellent option as initial
      therapy because of its strong antiretroviral action, its lower rate of adverse
      effect, and the smaller cost as compared to other regimens.

PMID- 11590494
TI  - Three-year effectiveness of highly active antiretroviral treatment in the
      Luxembourg HIV cohort.
AB  - Clinical trials have shown that highly active antiretroviral treatment (HAART) is
      able to reduce HIV plasma viral loads to undetectable in 70% to 90% of patients
      and to increase CD4 cell counts. HAART in community settings (i.e., nonclinical
      trial situations) is reported to be much less effective. STUDY DESIGN:
      Observational study. PURPOSE: The aim of our study was to evaluate the
      effectiveness of protease inhibitor (PI)-based HAART in the Luxembourg HIV cohort
      after 36 months of treatment in previously treated and untreated patients. The
      secondary aim was to identify surrogate markers associated with long-term
      virologic and immunologic outcomes. PATIENTS AND METHOD: Seventy-three PI-naive
      patients, who started on HAART, combining one PI and two nucleoside reverse
      transcriptase inhibitors (NRTIs),with a follow-up of 3 years, were evaluated with
      plasma viral load and CD4 cell counts every 3 months and were analyzed
      retrospectively. Patients who had been treated previously with NRTI (n = 48) were
      at a more advanced stage of disease. RESULTS: Overall, there was a mean decrease
      in viral load compared to baseline of -1.89 log RNA copies/mL (SD = 1.40) that
      persisted at month 36. Sixty-two percent (62%) of patients reached an
      undetectable viral load (i.e., below 500 copies/mL): 82% and 53% of NRTI-naive
      and NRTI-experienced patients, respectively (p =.013). CD4 cell counts increased
      progressively in both groups with a sustained effect (mean increase of 146
      cells/mL +/- 241) at month 36. NRTI-naive patients had a mean increase of 257
      cells/mL (SD = 305), in contrast to experienced patients who had an increase of
      108 cells/mL (SD = 206) at 3 years. Proportions of patients with a CD4 count
      under 200 cells/mL fell after 3 years for NRTI-naive (from 66% to 43%) and for
      experienced patients (from 32% to 13%). Predictors of short duration of viral
      load response were in decreasing order of importance: clinical AIDS, the use of
      saquinavir hard gel formulation as initial PI, and the number of NRTIs previously
      used. Viral load response was the only significant predictor of CD4 changes.
      CONCLUSION: In a community setting, effectiveness of PI-based HAART at 3 years is
      still achieved for most patients. NRTI-experienced patients have a good long-term
      response rate even if it is lower than NRTI-naive patients. A poor treatment
      response is associated with a more advanced stage of disease before HAART is
      introduced.

PMID- 11590493
TI  - Hospitalizations and costs of treatment for protease inhibitor-based regimens in
      patients with very advanced HIV-infection (CD4 < 50/mm(3)).
AB  - PURPOSE: To describe the cost of hospitalization and treatment in patients with
      very advanced disease who tart different regimens based on a protease inhibitor
      (PI). METHOD: An observational retrospective analysis was performed on data from
      a 48-week randomized, multicenter study. Analysis was based on a subgroup of
      centers that were geographically defined. Costs of ordinary hospital admissions
      and of antiretroviral treatment were considered. Incidence of hospitalization and
      number of days free from hospitalization during the period of observation were
      calculated. Cost and hospitalization measures were compared among patients
      receiving three different therapeutic regimens: only PI, PI plus one nucleoside,
      or PI plus two nucleosides. A multivariate analysis was used to assess cost
      differences, controlling for variables potentially able to influence outcome.
      RESULTS: Overall, among 166 patients starting PI (PI plus two nucleosides, 71;PI
      plus one nucleoside, 65; only PI, 30), 162 ordinary hospital admissions were
      observed during about 1 year of follow-up. Monthly rates of admission per person
      and incidence of first hospitalization on 100 person-months showed a clear
      inverse relationship with the number of drugs comprising the baseline treatment
      regimen, with the lower rates for the triple therapy group (0.06 and 3.9,
      respectively), intermediate values for the dual therapy group (0.10 and 8.1,
      respectively), and higher rates for the PI monotherapy group (0.15 and 13.7,
      respectively). The average number of days free from hospitalization per month was
      29.5 in the triple therapy group, 28.6 in the dual therapy group, and 27.9 in the
      monotherapy group. The results of cost analysis showed, despite higher cost of
      antiretroviral treatment, that global costs were progressively lower using
      regimens of increasing potency: Compared to PI monotherapy, global cost (costs of
      antiretroviral treatment and of hospitalizations combined) per month per patient
      was 31.9% lower for the triple therapy group and 19.3% lower for the dual
      therapy. Global cost for the triple therapy was 15.7% lower compared to global
      cost for dual therapy. After adjustment for CD4 count, AIDS status, and Karnofsky
      score, both hospitalization costs and global costs were significantly lower for
      triple therapy compared to monotherapy (p =.002 and.039, respectively).
      CONCLUSION: In advanced and nucleoside-experienced patients, PI-containing
      regimens have a differential impact according to the overall strength of the
      regimen, with the best effects on both hospitalizations and treatment costs
      obtained using PI within potent combination regimens.

PMID- 11590496
TI  - New agents for the inhibition of HIV replication.

PMID- 11590495
TI  - Efficacy of nelfinavir in patients switched from ritonavir/saquinavir combination
      antiretroviral therapy.
AB  - Based on available data and expert opinion, the IAS-USA treatment guidelines
      recommend "selective substitution" of the medication thought most likely to be
      causing a side effect for one that should have a different side effect profile.
      PURPOSE: This study evaluates the short-term virological efficacy of selective
      substitution with nelfinavir-nucleoside combination therapy in individuals with
      plasma viral RNA below 400 copies/mL. METHOD: This study involved a retrospective
      chart review at five large urban HIV Clinical practice settings and included 19
      patients taking combination therapy including ritonavir with saquinavir. We
      performed selective substitution with a nelfinavir combination. Our main outcome
      measure was plasma HIV-1 RNA (Amplicor) obtained during the period between weeks
      12 to 18. RESULTS: We identified 19 HIV-1-infected individuals with evidence of
      viral suppression as defined by a viral load below 400 copies/mL while taking
      dual nucleoside reverse transcriptase inhibitors with ritonavir/saquinavir.
      Reasons for switching included adverse effects (37%) or preference for nelfinavir
      due to the possibility of a better defined salvage regimen (63%). We defined a
      composite viral endpoint indicative of continued viral suppression using the
      first 12 to 18 weeks following the medication change. We found that 73%
      maintained undetectable viral loads (plasma HIV RNA below 400 copies/mL) during
      this period. CONCLUSION: These data suggest that any medication adjustment should
      be made cautiously, as there may be some potential risk in a substitution.
      Selective substitution of a medication that has undesirable side effects or other
      characteristics should be considered when the possible risks of the loss of viral
      suppression are outweighed by the potential benefits of that substitution.

PMID- 11590497
TI  - A practical guide to applying the intention-to-treat principle to clinical trials
      in HIV infection.
AB  - It is recommended that randomized controlled trials be analyzed on an intention
      to-treat (ITT) basis whereby patients are analyzed in the group to which they
      were originally assigned, irrespective of the treatment actually received.
      However, in trials of antiretroviral therapy, it is quite common for patients to
      withdraw from the trial, and information on virological or immunological
      endpoints may not be available. The way in which this missing information is
      dealt with in the analysis can have a large effect on the results of a trial and,
      therefore, the principle of ITT may be adhered to more closely in some studies
      than in others. This article describes some simple approaches commonly taken to
      impute missing data values and discusses the possible effects of these approaches
      on the results of a trial.

PMID- 11590498
TI  - US Public Health Service Task Force recommendations for the use of antiretroviral
      drugs in pregnant women infected with HIV-1 for maternal health and for reducing
      perinatal HIV-1 transmission in the United States, February 25, 2000.

PMID- 11590499
TI  - When to begin treatment, when to switch?: a brief summary of discussions between
      clinicians, researchers, and statisticians at a government-sponsored meeting.
      DIADS Workshop on Long-Term Studies of HIV Infections, January 11-13, 2000.
      Washington, DC.

PMID- 11590500
TI  - Low-dose daily subcutaneous interleukin-2 in combination with highly active
      antiretroviral therapy in HIV+ patients: a randomized controlled trial.
AB  - PURPOSE: Previous studies with intermittent interleukin-2 (IL-2) therapy using
      intermediate and high levels of IL-2 have demonstrated significant increases in
      the CD4 + T cell count in HIV-infected patients. Intermittent regimens are
      amenable to outpatient use, but severe adverse events are frequently experienced
      with intermediate- and high-dose levels of IL-2. Therefore in this study, the
      effect of daily, subcutaneous low-dose IL-2 therapy on safety and immunological
      endpoints was investigated to determine whether immunological benefit could be
      achieved without toxicity in HIV-infected patients also receiving highly active
      antiretroviral therapy (HAART). METHOD: A total of 115 patients were enrolled in
      the trial. Fifty-six asymptomatic HIV-infected patients who had CD4 + T cell
      counts less than 300 cells/microL at screening and a stable HIV viral load
      received low-dose IL-2 (1.2 million IU [MIU]/m 2 beginning dose) once daily in
      conjunction with HAART (IL-2 group). Fifty-nine patients received HAART alone
      (control group). RESULTS: A dramatic effect of IL-2 on the natural killer (NK)
      cell population was observed with mean increases of 156 cells/microL in the IL-2
      group compared to 19.93 cells/microL in the control group (p <.001).
      Additionally, IL-2-treated patients experienced a statistically significant
      increase in the mean percentage of CD4 + T cells (3.52% increase) when compared
      to control patients (1.33% increase) (p <.001). The expanded CD4 + T cell
      population was primarily of the naive phenotype, with mean increases of 4.53% for
      the IL-2 group and 0.31% for the control group (p <.001 for between-group
      difference). In addition, a higher proportion of IL-2-treated patients (67%)
      compared to control patients (33%) achieved increases of greater than 50% in the
      CD4+ T cell count (p =.08). Adverse events of grade 3 or grade 4 toxicity were
      infrequent in the current study and were substantially lower by comparison to
      those in studies of intermittent dose IL-2 therapy. Also, negligible changes in
      the HIV viral load from baseline to final measurement were observed in both
      groups. A trend toward a reduced number of modifications of antiretroviral
      therapy was apparent in the IL-2 group when compared to control patients.
      CONCLUSION: Daily, low-dose subcutaneous IL-2 therapy in conjunction with HAART
      is safe and well tolerated and is effective in expanding lymphocyte cell types
      including NK cells and naive T cells in individuals who have <300 CD4+ T cells.

PMID- 11590501
TI  - In vivo assessment of antiviral reactivity in chronic HIV infection.
AB  - PURPOSE AND METHOD: Chronic infection with HIV renders individuals incapable of
      mounting an effective host antiviral response, as defined by in vitro assays.
      Therefore, to determine whether antiviral reactivity could be detected in vivo,
      we interrupted effective antiviral treatment prospectively in nine chronically
      infected aviremic individuals. Low-dose interleukin-2 (IL-2) was administered
      before and after treatment interruption to compensate for any potential IL-2
      production deficiency. In vivo antiviral reactivity was monitored subsequent to
      the interruption of antiviral therapy via viral and lymphocyte dynamics. The
      study was terminated when the plasma HIV RNA concentration reached a plateau,
      defined as four successive determinations that were <25% from the mean. RESULTS:
      Plasma viral relapse occurred in all participants; reaching a peak concentration
      within 2.5 weeks. However, over the subsequent 2 weeks viremia was reduced an
      order of magnitude coincident with a 2-fold lymphocytosis of the CD8 + T cell
      subset. A second treatment interruption resulted in attenuation of the peak and
      trough virus concentrations by <10-fold in 3 of 4 participants, while the CD8 + T
      cell concentrations remained elevated. CONCLUSION: These findings indicate that
      chronic HIV infection prior to successful antiviral therapy does not preclude
      host antiviral reactivity. In addition, in vivo antiviral reactivity as revealed
      by viral and lymphocyte dynamics after antiviral treatment interruption can be
      useful to monitor the efficacy of different therapies.

PMID- 11590502
TI  - Use of sargramostim (rh-GM-CSF) as adjunctive treatment of fluconazole-refractory
      oropharyngeal candidiasis in patients with AIDS: a pilot study.
AB  - PURPOSE: Fluconazole-refractory mucosal candidiasis is a significant problem in
      patients with advanced HIV disease. Granulocyte-macrophage colony-stimulating
      factor (GM-CSF) is postulated to activate neutrophils, enhance phagocytosis, and
      increase intracellular killing of Candida species. The aim of this study was to
      evaluate the use of sargramostim (rh-GM-CSF) in combination with fluconazole for
      refractory mucosal candidiasis in patients with AIDS. METHOD: Patients with
      mycologically confirmed fluconazole-refractory oropharyngeal candidiasis who
      failed fluconazole 400 mg/day for a minimum of 7 days were enrolled, continued on
      fluconazole (400 mg/day), and received sargramostim 2.5 microg/kg/day for a
      minimum of 2 weeks. Patients were evaluated for clinical signs and symptoms of
      oropharyngeal candidiasis, and quantitative fungal cultures were taken at
      baseline and the end of weeks 1 and 2 of therapy. RESULTS: Eleven patients were
      entered, 3 out of 11 patients were cured, 6 were unchanged, and 2 were worse at
      the 2-week evaluation. Mycological response was seen in 7 out of 11 patients.
      CONCLUSION: In this small pilot study, sargramostim appears to exert a beneficial
      effect on the mucosal mycoflora and may be a possible alternative as adjunctive
      therapy in the management of fluconazole-refractory mucosal candidiasis in
      advanced HIV-positive patients.

PMID- 11590503
TI  - Problems with publishing results of interim analyses of randomized clinical
      trials.
AB  - PURPOSE: This purpose of this study was to illustrate how publication of interim
      analyses of randomized clinical trials (RCTs) can cause problems in the
      interpretation of final results. METHOD: The effect of publishing interim
      analyses on the results of a typical HIV RCT comparing regimens of registered
      antiretroviral drugs was illustrated using a simulation study. Simulations
      modeled an RCT comparing the effect of two treatment combinations on changes in
      log HIV viral load from baseline. Publication of interim results at 6 months was
      assumed to lead to 50% of patients switching from the poorer treatment if interim
      results were statistically significant (p <.05), 20% of patients switching from
      the poorer treatment if interim results were marginally significant (.05 < p
      <.20), and 10% of all patients switching treatment if interim results were not
      statistically significant. Three scenarios were simulated: a large treatment
      difference (0.4 log HIV viral load), a moderate difference (0.2 log), and no
      treatment difference (0.0 log). RESULTS: The simulation study showed that if the
      true treatment difference was large (0.4 log) the power of the trial was reduced
      from over 80% at 6 months to under 37% at 12 months. Furthermore, given the
      statistical significance of the interim analysis results at 6 months, the
      simulations illustrated that the trial results would appear similar at 12 months,
      regardless of the true underlying treatment difference. CONCLUSION: The
      simulations reinforce the fact that publication of interim analyses of RCTs can
      affect the future conduct of a trial and make interpretation of final results
      difficult.

PMID- 11590504
TI  - HIV lipodystrophy: a review.
AB  - The dramatic clinical benefit of highly active antiretroviral therapy has been
      offset, to an extent, by the development of unforeseen long-term toxicities. Of
      these, the HIV lipodystrophy syndrome is most prominent. The array of related but
      possibly separate manifestations includes fat deposition and atrophy and
      metabolic complications such as hyperlipidemias and diabetes mellitus. These have
      been attributed to the use of protease inhibitors, but other factors may be
      involved, particularly the use of nucleoside reverse transcriptase inhibitors,
      especially stavudine. The pathogenesis of any of the manifestations of the
      syndrome remains to be explained. The metabolic complications may respond to
      standard treatments, but most therapies directed at fat changes have been
      unsuccessful. This review will summarize the state of knowledge in the field.

PMID- 11590505
TI  - Vertical transmission of HIV in Africa: diagnostic testing and new interventions.

PMID- 11590506
TI  - Guidelines for the use of antiretroviral agents in pediatric HIV infection,
      January 7, 2000.

PMID- 11590507
TI  - Selected topics from the 13th International AIDS Conference, July 9-14, 2000.
      Duran, South Africa.

PMID- 11590508
TI  - Nelfinavir plus nevirapine plus two NRTIS as salvage therapy for HIV-infected
      patients receiving long-term antiretroviral treatment.
AB  - PURPOSE: To evaluate a rescue therapy involving nevirapine plus nelfinavir plus
      two nucleoside reverse transcriptase inhibitors (NRTIs) in patients with prior
      extensive antiretroviral therapy (AT) including protease inhibitors (PIs) but not
      nonnucleoside reverse transcriptase inhibitors (NNRTIs). METHOD: Patients with
      failing regimens were prospectively enrolled. According to genotypic profile at
      baseline, two groups were identified: a highly resistant (HR) group, which
      included strains resistant to PI and NRTI, and a moderate nonresistant group
      (MR), which showed resistance only to PI or NRTI or no resistance. RESULTS:
      Twenty-two individuals were included. Average time of AT prior to enrollment was
      3.7 years (range 1.4-7.6), median viral load 4.92 log(10) (interquartile range
      [IQR] 1.63 log(10)), and median CD4 cell count 64 cells/microL (IQR 94). After 16
      weeks of treatment, seven patients (31%) achieved virological response, five of
      them (22.7%) with <500 c/mL (bDNA). Fourteen patients were studied for
      resistance. The HR group showed a poorer response than the MR group (0 vs. 7
      responses; p =.034). CONCLUSION: We found a virological response in 31% of our
      patients, and mainly in those of the MR group some presented previous
      intolerance. These two factors probably reflect the number of drugs included in
      the rescue therapy to which the patient is sensitive. Treatment history as well
      as genotypic resistance assays are useful in identifying patients with the best
      chance of responding.

PMID- 11590509
TI  - Virological and immunological response to HAART therapy in a community-based
      cohort of HIV-1-positive individuals.
AB  - PURPOSE: To determine virological and immunological response to highly active
      antiretroviral therapy (HAART) and to investigate factors influencing response in
      a community-based setting. METHOD: Plasma HIV RNA levels and CD4 cell counts were
      studied in 168 unselected individuals starting HAART including indinavir or
      ritonavir or hard-gel saquinavir-containing regimens. RESULTS: Overall, 60% of
      the patients reduced their HIV RNA to below 500 Eq/mL, but half of them
      experienced a subsequent virologic rebound. Patients with higher baseline HIV
      RNA, higher baseline CD4 cell count, and simultaneous initiation of combination
      therapy and patients on indinavir or ritonavir regimen were more likely to have
      virologic response within 6 months since HAART initiation. Patients with lower
      baseline CD4 cell count and with lower rates of viral clearance had a higher
      probability of a subsequent virologic rebound. Forty percent of the patients had
      increased their CD4 cell counts by more than 100 cells/microL (immunologic
      response). The probability of immunologic response was independent of baseline
      HIV RNA levels and CD4 cell count; however, the more complete the virologic
      suppression, the higher the probability of immunologic response. Thirty percent
      of the patients had discordance between virologic and immunologic responses.
      CONCLUSION: The rate of virologic failure in this unselected group of patients
      was higher than that observed in randomized clinical trials, but only a minority
      (11%) of the patients were treatment naive. Starting combination therapy
      simultaneously and initiating antiretroviral therapy before advanced HIV disease
      has developed predict virologic response, whereas the magnitude of viral
      suppression predicts mid to long immunological response.

PMID- 11590510
TI  - Protease-sparing regimen in a real-life practice with naive patients: an equal
      opportunity approach?
AB  - PURPOSE: Proven clinical efficacy of protease-sparing regimens (PSR) has been
      shown. Concerns exist about broad applicability of these regimens in advanced
      naive patients. Recent reports have associated a rise in liver enzymes with nevi
      rapine; however, no data exist with efavirenz. METHOD: 17 consecutive
      antiretroviral-naive HIV patients were started on a PSR with efavirenz plus two
      nucleoside reverse transcriptase inhibitors. Baseline liver enzymes, serum CD38,
      CD4, and HIV viral load data were collected. Correlation between change in viral
      load and immune reconstitution on therapy were compared to baseline laboratory
      values. RESULTS: All patients had a mean viral load decrease of >2 logs,
      including patients with low initial CD4% or high viral load, and there was no
      increase of liver enzymes observed at a median follow-up of 42 weeks (range 17
      78). There was a perfect correlation between the change in viral load and the
      initial viral load (p <.0001, r = 1.00) including patients with viral load > or
      =100,000 copies/mL and CD4 count< or =50 (n = 5). Even patients with low initial
      CD4 had a significant percentage increase in CD4 count (p <.0002, r = 0.7880).
      CD38% showed a positive correlation with change in viral load (p =.046, r =
      0.522). CONCLUSION: All patients experienced a mean viral load decrease of >2
      logs (88% less than 400 copies/mL and 35% less than 20 copies/mL). There were no
      observed increases in liver enzymes. Patients with low CD4 counts, high initial
      viral load, or high CD38 expression still experienced a significant change in
      viral load.

PMID- 11590511
TI  - Therapeutic trials in HIV infection: which benefits for which patients?
AB  - PURPOSE: The purpose of our study was to make an assessment of the HIV patients'
      overall opinion of therapeutic trials, to analyze the motivations and the reasons
      linked to this perception, and to determine if their involvement in a therapeutic
      trial is a help or a hindrance to their treatment. METHOD: All the inpatients and
      outpatients attending the Dijon University Hospital AIDS day care unit during the
      first 4 months of 1999 were given an anonymous questionnaire designed to record
      the patients' attitudes toward therapeutic trials, their motivations, and the
      perceived risks. The questionnaire was often completed in consultation with a
      psychoanalyst. RESULTS: Two hundred and seven (207) patients were surveyed; 194
      of them had a favorable opinion of therapeutic trials. The main motivations to
      take part in a therapeutic trial were altruistic. In contrast, individualistic
      considerations and relational motivations (such as to modify the relationship
      between the caregiver and the patient) were more closely associated with a
      negative perception. CONCLUSION: Most of the patients will benefit or at least
      will not be harmed by being involved in a trial. However, the patients' attitudes
      toward the principle of therapeutic trials have to be determined before these
      patients are included in a given therapeutic trial. This is necessary to avoid
      the risk of subsequent medical care being altered because participation was
      either induced or compelled.

PMID- 11590512
TI  - Study of the validity of a questionnaire to assess the adherence to therapy in
      patients infected by HIV.
AB  - PURPOSE: The purpose of our study was to examine the validity of a questionnaire
      to detect nonadherence in HIV-infected patients under antiretroviral treatment.
      METHOD: This was a cross-sectional study to validate a diagnostic test.
      Participants consisting of 242 HIV-infected patients were elected by consecutive
      sampling in a hospital in Madrid. The validation standard was the pharmacy
      dispensing records with the cut point being 80% and 90% of delivered drugs.
      Sensitivity (S), specificity (SP), positive predictive value (PPV), and positive
      likelihood ratio (PLR) of the questionnaire were estimated. RESULTS: The mean age
      of the participants was 36.2 years old (SE 0.42), 55% were men, and 68.2% had
      used parenteral drugs. Eighty-three patients (34.3%) did not reach 80% of the
      prescribed dose and 129 patients (53.3%) did not reach 90%. In the 80% group, S
      was 25.3% (95% CI, 16.7%-36.2%),SP was 86.2% (95% CI, 79.6%-90.9%), PPV was 48.9%
      (95% CI, 33.5%-64.3%), and the PLR was 1.83 (95% CI, 1.07-3.13). In the 90%
      group, the S was 19.4% (95% CI, 13.4%-27.4%), SP was 84.0% (95% CI, 75.7%-90.0%),
      PPV was 58.1% (95% CI, 42.4%-72.6%), and PLR was 1.22 (95% CI, 0.70-2.12).
      CONCLUSION: The proposed questionnaire is not a reliable diagnostic method to
      detect nonadherence. It should only be incorporated into the daily clinical
      practice along with other methods of nonadherence measurement.

PMID- 11590513
TI  - Self-reported symptoms after initiation of a protease inhibitor in HIV-infected
      patients and their impact on adherence to HAART.
AB  - PURPOSE: The purpose of our study was to assess short-term self-reported symptoms
      in patients who were started on two nucleoside reverse transcriptase inhibitors
      and one protease inhibitor (PI) in the multicenter APROCO cohort (N = 336) and to
      assess the influence of these symptoms on adherence. METHOD: Adherence and
      patient's reported symptoms were measured at 1 and 4 months (M) after initiation
      of highly active antiretroviral therapy (HAART) through self-administered
      questionnaires. RESULTS: Most patients reported at least one symptom (94.0% at
      M1; 88.0% at M4); fatigue and diarrhea were the most often reported symptoms.
      Respectively, 81.3% and 75.0% of patients were strictly adherent to HAART during
      the 4 days prior to M1 and M4 visits. After adjustment for younger age, history
      of antiretroviral treatment, unstable housing, poor social support, and alcohol
      consumption, patients who reported a high number of symptoms at M1 were more
      likely to be nonadherent at M4 (odds ratio per symptom = 1.13; 95% CI = 1.03
      1.24). CONCLUSION: Patients reporting a high number of symptoms soon after HAART
      initiation are at higher risk of future nonadherence and could be targeted for
      interventions to achieve good levels of adherence and to improve treatment
      outcome.

PMID- 11590514
TI  - Antiretroviral treatments to reduce mother-to-child transmission of HIV.

PMID- 11590516
TI  - World Medical Association Declaration of Helsinki: ethical principles for medical
      research involving human subjects (revised October 7, 2000).

PMID- 11590515
TI  - Public Health Service Task Force recommendations for use of antiretroviral drugs
      in pregnant HIV-1-infected women for maternal health and interventions to reduce
      perinatal HIV-1 transmission in the United States (revised November 3, 2000).

PMID- 11590518
TI  - Circulating levels of interleukin-7 in antiretroviral-naive and highly active
      antiretroviral therapy-treated HIV-infected patients.
AB  - Interleukin (IL)-7 is a critical cytokine regulating T-lymphocyte development,
      regeneration, and function. PURPOSE: This study analyzes the endogenous IL-7
      production in HIV-infected patients receiving highly active antiretroviral
      treatment (HAART). METHOD: Plasma levels of IL-7 were measured by enzyme-linked
      immunosorbent assay (ELISA) in 11 patients with untreated advanced HIV disease,
      in 8 patients who successfully responded to HAART, and in 9 individuals with
      virological and immunological treatment failure. RESULTS: We found that in the
      patients with advanced HIV disease and no treatment IL-7 concentrations were
      elevated and were inversely related to both CD4 + and CD8 + T-cell counts. When
      IL-7 was assessed in treated patients, this cytokine was below the detection
      limit of the assay in all participants who responded to HAART. On the contrary,
      patients with evidence of HAART failure had increased concentrations of IL-7 that
      were comparable to those found in the untreated group with progressive disease.
      CONCLUSION: These data suggest that IL-7 may play a role in the immune
      reconstitution of T-cells during HIV infection, especially in the context of
      potent antiretroviral treatments.

PMID- 11590519
TI  - Nevirapine or efavirenz combined with two nucleoside reverse transcriptase
      inhibitors compared to HAART: a meta-analysis of randomized clinical trials.
AB  - PURPOSE: A meta-analysis of randomized controlled trials (RCTs) was performed to
      evaluate effectiveness and tolerability of triple antiretroviral therapy regimens
      in HIV-infected patients. METHOD: RCTs including the nonnucleoside reverse
      transcriptase inhibitors (NNRTIs) nevirapine (NVP) or efavirenz (EFV) compared to
      two nucleoside reverse transcriptase inhibitor (NRTI) regimens and to three-drug
      regimens based on two NRTIs and one protease inhibitor (PI; highly active
      antiretroviral therapy [HAART]) were analyzed by Peto's method. RESULTS: A
      significant virological response was observed in patients treated with NNRTIs
      (odds ratio [OR] 3.6; 95% CI, 2.2-6.0), particularly in naive patients (OR 7.4;
      95% CI, 4.1-13.5). A fair reduction of HIV disease progression was also observed
      in patients treated with NNRTIs (OR 0.8; 95% CI, 0.6-1.0). Moreover, a
      significantly lower rate of HIV progression was observed in patients with a CD4 +
      lymphocyte count below 100/mm(3). Five RCTs comparing two NRTIs and one NNRTI to
      HAART were subsequently evaluated. A slightly higher rate of virological response
      was observed with NNRTIs (OR 1.6; 95% CI, 1.1-2.1), whereas no difference was
      observed concerning progression of HIV disease. CONCLUSION: Antiretroviral
      therapy including NVP or EFV was more effective in reducing viral load than
      therapy with only two NRTIs and was slightly more effective than HAART.
      Effectiveness in delaying HIV disease progression was less evident, even though
      lower rate of progression was observed in patients with advanced HIV infection
      compared to two NRTIs alone.

PMID- 11590517
TI  - A randomized trial of nelfinavir, ritonavir, or delavirdine in combination with
      saquinavir-SGC and stavudine in treatment-experienced HIV-1-infected patients.
AB  - PURPOSE: To evaluate the 24-week impact of saquinavir-enhancing antiretroviral
      therapy on viral replication in patients previously treated with nucleoside
      analogues with or without prior saquinavir hard-gel capsules (HGC). METHOD:
      Patients were randomized in three groups to receive the following: Group 1
      nelfinavir (750 mg tid), saquinavir soft-gel capsule (SGC) (800 mg tid), and
      stavudine (40 mg bid); Group II-ritonavir (400 mg bid), saquinavir-SGC (400 mg
      bid), and stavudine (40 mg bid); or Group III-delavirdine (400 mg tid),
      saquinavir-SGC (800 mg tid), and stavudine (40 mg bid). Viral loads, CD4 count,
      and safety were assessed over a 24-week period with an additional 6-month follow
      up. RESULTS: 73 patients received randomized therapy; 14 of whom were SQV naive,
      with a median baseline viral load of 3.6 log(10) and a CD4 count of 370
      cells/mm(3). By 6 months, the median decreases in plasma viral loads were 0.26,
      0.71, and 0.29 log(10) copies/mL for groups I, II, and III, respectively. The
      median increases in CD4 counts, for groups I, II, and III, were 52, 40, and 69
      cells/mm(3) at 6 months, respectively. Changes in viral load and CD4 counts at 6
      months and 1 year were not significantly different between the treatment groups.
      More patients discontinued therapy in the ritonavir arm (35%) for drug
      intolerance or toxicity compared to either the nelfinavir or delavirdine arms
      (15% and 5%, respectively). In a multivariate analysis, baseline viral load,
      younger age, and baseline saquinavir resistance were significantly associated
      with detectable viral load at 24 weeks. CONCLUSION: The use of antiretroviral
      agents that pharmacokinetically boost saquinavir levels has a modest benefit in
      saquinavir-experienced patients.

PMID- 11590520
TI  - The insufficient suppression of viral load by saquinavir hard gel is reversible:
      a retrospective cohort study.
AB  - PURPOSE: To assess the effect of changing antiretroviral therapy in patients
      initially treated with saquinavir hard gel capsule (hgc). METHOD: A retrospective
      cohort study comparing the virological and immunological responses in
      antiretroviral-naive patients initially treated with a regimen of saquinavir-hgc,
      zidovudine, and lamivudine, with patients receiving either ritonavir or indinavir
      on a background of zidovudine and lamivudine. RESULTS: Twenty-nine patients
      starting with saquinavir-hgc as the protease inhibitor (PI) component were
      compared to 58 patients starting with ritonavir (n = 16) or indinavir (n = 42).
      Median follow-up time was 30 and 33 months, respectively. Twelve, 18, 24, and 30
      months after starting a regimen including saquinavir-hgc, 72%, 50%, 4%, and 0% of
      patients still received this PI. At these time points, 35%, 24%, 59%, and 74% of
      the patients in the saquinavir group obtained an HIV-RNA <500 copies/mL compared
      to 76%, 72%, 66%, and 65% in the indinavir/ritonavir group. No significant
      difference in CD4 count between the two groups was observed. CONCLUSION: We found
      that saquinavir-hgc, in combination with nucleoside reverse transcriptase
      inhibitors, suppressed viral load insufficiently in HIV patients naive to
      antiretroviral therapy. However, the suboptimal effect of saquinavir-hgc seems
      reversible after optimizing the antiretroviral regimen, at least for the short
      term.

PMID- 11590521
TI  - Evaluation of the Patient Medication Adherence Questionnaire as a tool for self
      reported adherence assessment in HIV-infected patients on antiretroviral
      regimens.
AB  - PURPOSE: Adherence to antiretroviral medications is critically important for the
      success of therapy in patients treated for HIV infection. Patient self-report is
      a simple method to measure and explore adherence. Even though a variety of
      surveys have been developed to monitor self-reported adherence, there is no
      standardized instrument that may be used in routine clinical practice. The
      usefulness of the Patient Medication Adherence Questionnaire (PMAQ) was evaluated
      in HIV-infected patients on protease inhibitor (PI)-containing regimens. METHOD:
      Data from 149 patients were collected. Study participants completed the PMAQ and
      provided blood samples to measure plasma HIV-1 RNA concentrations and trough
      plasma levels of PI. Patients were considered adherent if they had a virologic
      response and/or had an adequate trough plasma level of PI. RESULTS: A close
      relationship was found between patient reports of adherence during the previous 4
      days and objective measures such as HIV RNA level and plasma levels of PI.
      Motivation with regard to antiretroviral treatment, confidence in personal
      skills, and an optimistic attitude to life were identified as important
      determinants of adherence. On the other hand, sociodemographic background, social
      support, alcohol and illicit drug use, bothersome symptoms, and depression were
      not associated with a lower medication adherence. CONCLUSION: Patients'
      psychological and behavioral factors are central in the acceptance and adherence
      to antiretroviral therapy. To improve the feasibility and the reproducibility of
      the PMAQ, we propose a revised form of the PMAQ, focusing on the variables
      identified as strong predictors of adherence.

PMID- 11590522
TI  - Effect of HAART on health status and hospital costs of severe HIV-infected
      patients: a modeling approach.
AB  - PURPOSE: The purpose of this study was to assess the impact of highly active
      antiretroviral therapy (HAART) on health status and hospital costs in severe HIV
      infected patients who were followed in a French hospital. METHOD: The first 500
      patients who received HAART, with CD4 + cell count below 250/mm(3), were
      considered. Evolution of the distribution of patients among different health
      states, including death, was modeled through a continuous time Markov model.
      Hospital financial charges and antiretroviral treatment costs were computed.
      Health states defined by both CD4 counts and viral load were used to show
      clinical changes in the patient population over a 14-month period after HAART
      initiation. The economic impact of HAART initiation was assessed using a
      simplified model based on CD4 counts only over two 14-month periods, before and
      after initiation. RESULTS: Between day 0 and month 14, the proportion of patients
      in the least severe state (CD4 + >100/mm(3) and viral load<500 copies/mL)
      increased from 1% to 50%, and the proportion with more than 100 CD4 + cells/mm(3)
      increased from 17% to 80%. Antiretroviral treatments amounted to Fr 2,141 per
      patient-month before HAART initiation and to Fr 3,093 after. Conversely, hospital
      charges fell from Fr 5,138 per patient-month to Fr 3,136. CONCLUSION: Our model
      gives a representation of the effect of HAART on (1) the improvement of patients'
      health status, (2) the increase of treatment costs, and (3) the reduction of
      hospital financial charge. Important savings in hospital charges can compensate
      for the extra cost associated with the initiation of HAART.

PMID- 11590523
TI  - Adherence to antiretroviral therapy: appropriate use of self-reporting in
      clinical practice.
AB  - PURPOSE: This study investigated the factors that may affect adherence to
      antiretroviral therapy in people with HIV infection and compared the use of three
      self-report tools to determine client adherence. METHOD: A descriptive, cross
      sectional study of 260 HIV-infected clients attending nine HIV outpatient centers
      in England was conducted using researcher-administered instruments. Self-reports
      of adherence were assessed using the Morisky Medication Adherence Scale (MMAS),
      Reported Adherence to Medication Scale (RAM), and the Patient Adjustment to
      Medication Scale (PAM). RESULTS: Univariate analysis of clients' self-reports
      indicated a number of associations with adherence. Significant associations with
      less adherent behavior identified by two or more self-report tools were the
      reported use of recreational drugs, p =.001; living alone, p =.041; feeling
      depressed, p =.02; being influenced by the media, p =.037; and lack of a close
      confidant, p =.037. Greater adherence was associated with clients reporting a
      positive mental attitude to HIV infection, p =.038. Principal component analysis
      (PCA) of each self-report tool identified two well-recognized constructs:
      intentional nonadherence and unintentional nonadherence. In addition, a third
      construct of following instructions was identified from PAM, a scale developed by
      the authors. Subsequent regression analysis failed to confirm the associations
      with adherence suggested by the univariate analysis. CONCLUSION: This study
      suggests that the design and use of self-report tools to identify client's
      adherence to complex antiretroviral regimens may need to measure individual
      constructs of adherence to accurately assess adherence behavior.

PMID- 11590524
TI  - Comparative CD4 T-cell responses of reverse transcriptase inhibitor therapy with
      or without nelfinavir matched for viral exposure.
AB  - BACKGROUND: Therapy of HIV infection with protease inhibitors (PIs) may be
      associated with improvements in CD4 T-cell number via a mechanism that is
      independent of effects on plasma viral load (VL). PURPOSE: To compare CD4
      responses of patients who receive reverse transcriptase inhibitor (RTI) therapies
      with or without a PI, matched for viral exposure. METHODS: Patient data were
      analyzed from two prospective randomized trials of antiviral therapy with or
      without nelfinavir. Total viral exposure over 24 weeks was estimated by viral
      area under the curve (AUC), which reflects baseline viral load, slope of
      virologic decay, viral nadir, and duration of suppression. Patients were
      stratified into quartiles on the basis of viral AUC, and CD4 T-cell responses
      were evaluated between PI-containing and RTI-only treatment groups within each
      quartile. RESULTS: In both trials, patients receiving nelfinavir had greater CD4
      T-cell increases than patients receiving RTI alone. Analysis of variance modeling
      revealed increased CD4 T-cell responses in PI-treated groups at all time points
      after the second week. These differences were significant (p <.05) at weeks 12,
      24, 28, 32, 36, 40, and 48 in one study, and weeks 1, 2, 4, 6, 8, 12, 16, 20, 24,
      28, 32, 36, and 44 in the other. Within quartiles matched for viral AUC, absolute
      CD4 T-cell change from baseline was greater in the PI-treated patients at 84%
      (101/120) of time points analyzed. CONCLUSION: Nelfinavir-containing therapy is
      associated with enhanced increases in CD4 T-cell number compared to RTI therapy
      alone with equivalent antiviral effect. These data suggest that PIs influence CD4
      T-cell number through a nonvirologic effect.

PMID- 11590525
TI  - Selected topics from the 38th annual meeting of the Infectious Diseases Society
      of America, September 7-10, 2000, New Orleans, Louisiana and selected topics from
      the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy,
      September 17-20, 2000, Toronto, Ontario, Canada.

PMID- 11590526
TI  - Microbicide research and development--where to?
AB  - PURPOSE: Against the backdrop of increasing numbers of HIV infections in women
      and the limitations of current safer sex messages, several calls have been made
      for the development of women-initiated methods of prevention as an essential
      component of the armamentarium to reduce women's vulnerability of acquiring
      infection with HIV. An effective microbicide is a critical survival tool in
      instances and situations where existing proven prevention strategies have failed
      to be adopted. METHOD: The results of published N-9 clinical trials in terms of
      anti-HIV activity, safety data, and anti-sexually transmitted infection (STI)
      activity are discussed. RESULTS: There is no evidence of efficacy against HIV in
      three clinical trials, there is scanty evidence for protection against STIs, and
      there is considerable evidence of dose-related adverse effects. CONCLUSION:
      During this time, a vast array of potential microbicides with differing modes of
      action have been discovered, and some have undergone preclinical and early
      clinical testing. Effort, time, and resources might be better spent on advancing
      preclinical and clinical testing of these other candidate microbicides.

PMID- 11590527
TI  - Combination therapy with indinavir, ritonavir, and delavirdine and nucleoside
      reverse transcriptase inhibitors in patients with HIV/AIDS who have failed
      multiple antiretroviral combinations.
AB  - PURPOSE: Ritonavir (RTV) and delavirdine (DLV) are inhibitors of cytochrome P450
      (CYP) 3A4, the specific CYP that metabolizes indinavir (IDV). We hypothesized
      that patients who have failed multiple therapies containing protease inhibitors
      would still respond to IDV if high plasma concentrations were achieved. We
      retrospectively examined the antiviral efficacy of the combination of RTV, DLV,
      and IDV in heavily antiretroviral-experienced patients. METHOD: A chart review of
      patients treated with IDV/RTV/DLV and two nucleoside reverse transcriptase
      inhibitor (NRTI) drugs was performed. Only patients who failed at least three
      highly active antiretroviral therapy (HAART) regimens and remained on IDV/RTV/DLV
      therapy for at least 2 months were included. Plasma concentrations for IDV and
      RTV were obtained if patients were still on therapy. RESULTS: Ten participants
      were identified who qualified for this study. The median plasma HIV RNA prior to
      initiating IDV/RTV/DLV was 359,300 copies/mL. Nine of the 10 patients had failed
      nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens in the
      past. Eight out of 10 patients had at reduction in HIV RNA. Four of eight
      patients maintained the 1 log(10) reduction in HIV RNA past 6 months. Mean CD4
      cell count increased from 142+/-99 to 273+/-126 cells/mm(3). Genotypic data
      available on six patients showed multiple protease gene mutations. Plasma
      concentration of IDV in three patients (two troughs and one 7 hours postdose)
      were >1,000 ng/mL. CONCLUSION: Our data suggests that in heavily antiretroviral
      drug-treated patients, partial antiretroviral response to RTV/IDV/DLV can still
      be achieved. The use of IDV/RTV/DLV and two NRTIs as salvage therapy has merit in
      patients who have no viable treatment options. A prospective trial utilizing this
      drug combination is warranted.

PMID- 11590529
TI  - Improving participation in HIV clinical trials: impact of a brief intervention.
AB  - PURPOSE: To determine if a brief intervention that provides information about
      AIDS clinical trials to HIV-infected patients at the initiation of primary care
      increases the participation of women, persons of color, and injection drug users
      (IDUs) in clinical trials. METHOD: 196 outpatients beginning HIV primary care at
      a municipal hospital were followed from September 1994 to April 1996. During the
      intake assessment, each patient met briefly with a research assistant who
      described the purpose, role, and availability of clinical trials. Contacts for
      further information about trials were given to patients who expressed interest.
      At the end of the 20-month period, enrollment rates of all patients, including
      women, persons of color, and IDUs, into clinical trials were compared with
      previously published enrollment rates of patients at the same hospital but prior
      to the development of this brief intervention. RESULTS: The characteristics of
      the 196 HIV-infected patients were: 27% women; 47% IDUs; 14% gay/bisexual men;
      and 76% persons of color. Overall enrollment in AIDS clinical trials was 14.8%
      during the 20-month follow-up period. There was no significant difference in
      participation rates between males and females (p =.20), whites and persons of
      color (p =.71), and IDUs compared with non-IDUs (p =.90), whereas previously
      published data had shown significantly higher enrollment rates among males,
      whites, and non-IDUs. CONCLUSION: Providing all HIV-infected patients with
      information about the meaning, role, and availability of AIDS clinical trials at
      the initiation of HIV primary care reduces differences in participation rates by
      gender, race, and history of drug use.

PMID- 11590528
TI  - Switch to efavirenz in a protease inhibitor-containing regimen.
AB  - PURPOSE: This report evaluated the efficacy and safety of switching from a
      protease inhibitor (PI)-containing HIV treatment regimen to an efavirenz (EFV)
      containing regimen. METHOD: We retrospectively analyzed data from 64 patients,
      with a plasma viral load (VL) less than 50 copies/mL and CD4+ counts >200
      cells/mL at baseline, who had been taking a regimen consisting of a PI and two
      nucleoside reverse transcriptase inhibitors (NRTIs; d4T/3TC [n = 45]; AZT/3TC [n
      = 19]) for a median of 27.5 months (range, 6-41 months) and who chose to
      substitute EFV for the PIs in the regimens. Statistical analyses were performed
      by Wilcoxon test. Fat atrophy was evaluated by physician's assessment and
      patients' subjective self-estimation with the criteria of well being and body
      state. RESULTS: 57 patients completed 36 weeks on the EFV regimen; 4 patients
      changed therapy but continued EFV, 2 moved to another area, and 1 discontinued
      EFV. During the first weeks of therapy, 56.3% of patients suffered from moderate
      nervous system symptoms. The plasma VL of 63 patients remained at <50 copies/mL
      at final analysis. Compared with time of switching to EFV, analysis at 36 weeks
      showed no statistically significant change from 626+/-283 to 643+/-296 cells/mL
      in mean absolute CD4+ cells and a statistically significant increase from 26.8+/
      9.6% to 28.0+/-9.1% in relative CD4+ cells. There was a statistically significant
      reduction in relative CD8+CD38+ from 62.2+/-16.3% at time of switching to EFV to
      55.1+/-15.0% at week 36. At baseline, 27 patients suffered from lipodystrophy,
      including fat atrophy and fat accumulation. After 36 weeks, nine patients showed
      intensified fat atrophy. In contrast, five patients improved their state
      concerning fat redistribution and 13 patients showed no alterations. CONCLUSION:
      The switch to a non-PI-containing regimen with EFV offers a good drug alternative
      for patients with suppressed viral load, problems of adherence, and/or adverse
      events due to PIs but not for patients suffering from lipoatrophy caused by
      nucleoside reverse transcriptase inhibitors. The intention of such a switch aims
      at the avoidance of fatal mutations in HIV.

PMID- 11590530
TI  - Effect of prior nucleoside use on the two-year virological response to an initial
      protease inhibitor regimen in HIV-infected patients.
AB  - PURPOSE: This retrospective study investigates the effect of prior nucleoside
      (nucleoside reverse transcriptase inhibitor [NRTI]) experience on 2-year
      virologic response to an initial protease inhibitor-highly active antiretroviral
      therapy (PI-HAART) regimen. METHOD: 152 patients who started a PI (excluding
      saquinavir hard gel capsule [hgc] as a sole PI) with two NRTIs between January
      1996 and May 1998 at two HIV treatment sites were included. RESULTS: 109 patients
      (71%) were NRTI experienced. 106 patients received two new NRTIs, and 32 received
      one new NRTI. Overall, 51% of patients had a virologic response (HIV viral load
      <400 copies/mL); the mean follow-up was 28 months. Virologic response was
      associated with the use of at least one new NRTI (relative risk [RR] 2.1; p
      =.031) but not with prior NRTI experience (p =.19). A complete virologic response
      was most likely to occur when two new NRTIs were used (RR 2.3) rather than one
      new NRTI (RR 1.8), but this was not significant (p =.12). CONCLUSION: This study
      suggests that prior nucleoside experience is not a key predictor of 2-year
      virologic response in patients who receive at least one new NRTI in an initial PI
      HAART regimen.

PMID- 11590531
TI  - Selected topics from the 8th Conference on Retroviruses and Opportunistic
      Infections. February 4-8, 2001. Chicago, Illinois.

PMID- 11590532
TI  - Guidelines for the use of antiretroviral agents in HIV-infected adults and
      adolescents. February 5, 2001.

PMID- 11590533
TI  - GW420867X administered to HIV-1-infected patients alone and in combination with
      lamivudine and zidovudine.
AB  - PURPOSE: GW420867X is a nonnucleoside inhibitor of HIV-1 reverse transcriptase.
      The primary objective was to assess the safety of GW420867X in HIV-1-infected
      patients. The secondary objectives were to assess the effect of GW420867X on
      plasma HIV-1 RNA and viral genotype and phenotype and to examine the
      pharmacokinetics of GW420867X in HIV-1-infected patients. METHOD: HIV-1-infected
      patients were randomized to GW420867X 50 mg/day, 100 mg/day, or 200 mg/day from
      days 1-28 (n = 15 per group). Lamivudine (3TC) plus zidovudine (ZDV) was added
      from days 8-28. A control group (n = 15) received GW420867X, 3TC, and ZDV
      placebos. RESULTS: Plasma HIV-1 RNA and CD4+ counts improved in the GW420867X
      groups at days 8 and 28. No significant development of drug resistance was
      detected. Median observed peak GW420867X concentration (C(max)) generally
      occurred at 2 hours. The area under the curve over the dosing interval (AUCtau)on
      day 14 increased less than proportionally to dose, suggesting there was increased
      clearance and/or decreased absorption. Mean trough GW420867X concentrations were
      many fold above the in vitro IC(50) in the presence of human serum proteins.
      Seven of 15 patients on 50 mg GW420867X, 8/15 on 100 mg GW420867X, 12/15 on 200
      mg GW420867X, and 8/15 on placebo reported drug-related adverse events.
      CONCLUSION: GW420867X was well tolerated and has potent antiretroviral activity
      alone and in combination with 3TC plus ZDV.

PMID- 11590534
TI  - Efficacy of nevirapine-based HAART in HIV-1-infected, treatment-naive persons
      with high and low baseline viral loads.
AB  - PURPOSE: The objective of this analysis was to assess the efficacy of
      nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing, protease
      inhibitor (PI)-sparing, three-drug highly active antiretroviral therapy (HAART)
      in HIV- 1-infected, treatment-naive patients with high and low baseline viral
      loads. METHOD: A composite analysis was performed of clinical studies including
      the NNRTI nevirapine that were presented at international conferences between
      1998 and October 2000. In all of the studies, nevirapine was administered in
      combination with two nucleoside reverse transcriptase inhibitors (NRTIs). For a
      study to be included in the analysis, more than 25% of participants must have had
      baseline viral loads >100,000 copies/mL, and more than 25% of participants must
      have had viral loads <100,000 copies/mL. RESULTS: After 6 months, 139 of 156
      (89%) and 82 of 99 (83% ) patients in the low and high baseline viral load
      groups, respectively, had on-treatment viral loads <200 to 500 copies/mL
      (depending on assay used). After 12 months, 95 of 124 patients (77%) with lower
      baseline viral loads and 63 of 76 patients (83%) with high baseline viral loads
      had on-treatment viral loads below the limit of quantification. CONCLUSION:
      Baseline viral load does not affect virologic outcome in HIV-1-infected,
      antiretroviral-naive participants treated with nevirapine-containing, PI-sparing
      HAART.

PMID- 11590535
TI  - Self-reported nonadherence with antiretroviral drugs predicts persistent
      condition.
AB  - PURPOSE: To assess variables predictive of nonadherence persisting over time in
      HIV-infected people treated with highly active antiretroviral therapy. METHOD:
      Prospective study of consecutive HIV-infected patients who were prescribed
      ritonavir- or indinavir-containing regimens in a university-based HIV clinic in
      Rome. A patient questionnaire assessing knowledge of treatment regimen, adherence
      behavior, reasons for taking and missing therapy, factors influencing adherence,
      and health behaviors was administered at baseline and 1 year later. A predose
      protease inhibitor plasma level was measured concurrently. Persistent
      nonadherence was defined as patient self-reported nonadherence both at enrollment
      and at follow-up questionnaires. RESULTS: From April 1998 to July 1998, 140
      patients were enrolled into the study. At follow-up, 10% remained persistently
      nonadherent, and 15% of the previously adherent patients became nonadherent. On
      bivariate analysis, being less than 35 years old (odds ratio [OR] 8.9; 95% CI 1.8
      43.1; p =.002), self-reporting nonadherence at enrollment (OR 14.5; 95% CI 3.5
      5.8; p <.001), and having experienced "a fair amount" or "a lot" of vomiting (OR
      11.1;95% CI 1.6-74.7; p =.02) or pruritus (OR 16.4; 95% CI 2.6-102.8; p =.004)
      during the 4 weeks before enrollment were significantly correlated to persistent
      nonadherence. CONCLUSION: Previous self-reported nonadherence was a strong
      predictor of persistent nonadherence during follow-up. Moreover, being of younger
      age and self-reporting vomiting or pruritus were also associated with a higher
      risk of nonadherence persisting over time.

PMID- 11590536
TI  - Progression to AIDS or death as endpoints in HIV clinical trials.
AB  - PURPOSE: To assess progression to AIDS or death from month 4 after a protease
      inhibitor-containing regimen is initiated in a cohort of 1,281 patients. METHOD:
      We used Kaplan-Meier estimates of probability of clinical progression. RESULT: At
      month 4, most patients had an HIV-1 RNA plasma value below 500 copies/mL (78%)
      and a CD4 cell count above 300 cells/mm(3) (62%). Starting from month 4, clinical
      progression at 1 and 2 years of follow-up was low (<3% at 1 year) in patients
      with HIV RNA <500 copies/mL or 500-10,000 copies/mL and in patients with CD4
      between 50 and 300 cells/mm(3) or >300 cells/mm(3). A higher risk of clinical
      progression (> or =10% at 1 year) was evidenced only in patients with poor
      response to antiretroviral therapy, that is, with CD4 <50 cells/mm(3) or CD4
      between 50-300 cells/mm(3) together with an HIV RNA >10,000 copies/mL.
      CONCLUSION: In patients currently on antiretroviral therapy, clinical trials with
      clinical progression as endpoint are almost not feasible, except in patients with
      a poor immunovirological response to first- or second-line HAART.

PMID- 11590537
TI  - Updated guidelines for managing HIV in pregnancy from the USPHS Task Force.

PMID- 11590538
TI  - Lipodystrophy in 685 HIV-1-treated patients: influence of antiretroviral
      treatment and immunovirological response.
AB  - PURPOSE: To describe the clinical features in HIV-1-infected patients treated
      with protease inhibitors (PIs) or not, and to determine factors related to
      occurrence of lipodystrophy (LD). METHOD: We performed a cross-sectional analysis
      of 685 treated HIV-1-infected patients that were routinely followed in 6 Paris
      hospital centers between January and May 1999. Demographic data, familial and
      personal vascular risk factors, history of antiretroviral treatment, HIV plasma
      viral load, CD4 cell count, and metabolic data were collected. Clinical
      examination was based on an assessment of changes in abdominal, dorso-cervical,
      and breast girth and wasting of the limbs, face, and skin as quoted by the
      clinician. RESULTS: The mean age at inclusion in the study was 38 years; 29.5%
      were women. At study assessment, 77.5% of patients were PI-treated and 22.5% had
      never received a PI. LD was observed in 403 (58.8%) patients, of whom 340 were
      currently receiving a PI and 63 had never received a PI. More than half of the
      lipodystrophic patients had a mixed form (53.9%), while 25.3% were classified as
      exclusive lipoatrophic and 20.8% as exclusive hypertrophic. In multivariate
      analysis, older age, duration of antiretroviral treatment (ART), antiretroviral
      combinations including stavudine, antiretroviral combinations including a PI,
      AIDS status, and a low HIV RNA were independently associated with occurrence of
      LD. CONCLUSION: LD is frequently observed in PI-treated patients, but it is also
      observed in patients receiving an ART regimen without PIs. Our study suggests
      different underlying mechanisms, because immunovirological response to treatment
      as well as certain therapies were linked to the occurrence of LD. This hypothesis
      would be best clarified in a large prospective cohort of naive patients.

PMID- 11590539
TI  - Antiretroviral Resistance Mutations (revised April 2001).

PMID- 11590540
TI  - Tuberculosis and HIV infection: epidemiology, immunology, and treatment.
AB  - Tuberculosis and HIV have combined to present a major threat to global public
      health. Each disease has a negative effect on the other, and mortality in
      patients with both tuberculosis and HIV is higher than that caused by either
      condition alone. In regions such as sub-Saharan Africa, as many as a third or
      more of all patients with tuberculosis have concomitant HIV infection. In urban
      centers in developed nations, HIV co-infection may also be quite common.
      Treatment of latent tuberculosis infection in persons with HIV is successful in
      preventing many cases of active disease, and newer ultra-short course regimens,
      such as those consisting of 2 months of rifampin and pyrazinamide, should aid in
      this effort. Diagnosis and treatment of active tuberculosis in HIV-infected
      patients may be difficult. Although treatment of active tuberculosis is generally
      successful in patients with HIV, drug interactions between anti-tuberculosis
      medications and antiretrovirals often complicate the matter, and expert guidance
      should be sought for proper management.

PMID- 11590541
TI  - Selected topics from the 8th Conference on Retroviruses and Opportunistic
      Infections. February 4-8, 2001. Chicago, Illinois.

PMID- 11590542
TI  - Active hepatitis G virus infection in perinatally HIV-infected children.

PMID- 11590543
TI  - Mutations in CGI-58, the gene encoding a new protein of the
      esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome.
AB  - Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive form of nonbullous
      congenital ichthyosiform erythroderma (NCIE) that is characterized by the
      presence of intracellular lipid droplets in most tissues. We previously localized
      a gene for a subset of NCIE to chromosome 3 (designated "the NCIE2 locus"), in
      six families. Lipid droplets were found in five of these six families, suggesting
      a diagnosis of CDS. Four additional families selected on the basis of a confirmed
      diagnosis of CDS also showed linkage to the NCIE2 locus. Linkage-disequilibrium
      analysis of these families, all from the Mediterranean basin, allowed us to
      refine the NCIE2 locus to an approximately 1.3-Mb region. Candidate genes from
      the interval were screened, and eight distinct mutations in the recently
      identified CGI-58 gene were found in 13 patients from these nine families. The
      spectrum of gene variants included insertion, deletion, splice-site, and point
      mutations. The CGI-58 protein belongs to a large family of proteins characterized
      by an alpha/beta hydrolase fold. CGI-58 contains three sequence motifs that
      correspond to a catalytic triad found in the esterase/lipase/thioesterase
      subfamily. Interestingly, CGI-58 differs from other members of the
      esterase/lipase/thioesterase subfamily in that its putative catalytic triad
      contains an asparagine in place of the usual serine residue.

PMID- 11590544
TI  - Hermansky-Pudlak syndrome type 3 in Ashkenazi Jews and other non-Puerto Rican
      patients with hypopigmentation and platelet storage-pool deficiency.
AB  - Hermansky-Pudlak syndrome (HPS), consisting of oculocutaneous albinism and a
      bleeding diathesis due to the absence of platelet dense granules, displays
      extensive locus heterogeneity. HPS1 mutations cause HPS-1 disease, and ADTB3A
      mutations cause HPS-2 disease, which is known to involve abnormal intracellular
      vesicle formation. A third HPS-causing gene, HPS3, was recently identified on the
      basis of homozygosity mapping of a genetic isolate of HPS in central Puerto Rico.
      We now describe the clinical and molecular characteristics of eight patients with
      HPS-3 who are of non-Puerto Rican heritage. Five are Ashkenazi Jews; three of
      these are homozygous for a 1303+1G-->A splice-site mutation that causes skipping
      of exon 5, deleting an RsaI restriction site and decreasing the amounts of mRNA
      found on northern blotting. The other two are heterozygous for the 1303+1G-->A
      mutation and for either an 1831+2T-->G or a 2621-2A-->G splicing mutation. Of 235
      anonymous Ashkenazi Jewish DNA samples, one was heterozygous for the 1303+1G-->A
      mutation. One seven-year-old boy of German/Swiss extraction was compound
      heterozygous for a 2729+1G-->C mutation, causing skipping of exon 14, and
      resulting in a C1329T missense (R396W), with decreased mRNA production. A 15-year
      old Irish/English boy was heterozygous for an 89-bp insertion between exons 16
      and 17 resulting from abnormal splicing; his fibroblast HPS3 mRNA is normal in
      amount but is increased in size. A 12-year-old girl of Puerto Rican and Italian
      background has the 3,904-bp founder deletion from central Puerto Rico on one
      allele. All eight patients have mild symptoms of HPS; two Jewish patients had
      received the diagnosis of ocular, rather than oculocutaneous, albinism. These
      findings expand the molecular diagnosis of HPS, provide a screening method for a
      mutation common among Jews, and suggest that other patients with mild
      hypopigmentation and decreased vision should be examined for HPS.

PMID- 11590545
TI  - Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal
      dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner, Sebastian,
      Epstein, and Alport-like syndromes.
AB  - May-Hegglin anomaly (MHA) and Fechtner (FTNS) and Sebastian (SBS) syndromes are
      autosomal dominant platelet disorders that share macrothrombocytopenia and
      characteristic leukocyte inclusions. FTNS has the additional clinical features of
      nephritis, deafness, and cataracts. Previously, mutations in the nonmuscle myosin
      heavy chain 9 gene (MYH9), which encodes nonmuscle myosin heavy chain IIA
      (MYHIIA), were identified in all three disorders. The spectrum of mutations and
      the genotype-phenotype and structure-function relationships in a large cohort of
      affected individuals (n=27) has now been examined. Moreover, it is demonstrated
      that MYH9 mutations also result in two other FTNS-like macrothrombocytopenia
      syndromes: Epstein syndrome (EPS) and Alport syndrome with macrothrombocytopenia
      (APSM). In all five disorders, MYH9 mutations were identified in 20/27 (74%)
      affected individuals. Four mutations, R702C, D1424N, E1841K, and R1933X, were
      most frequent. R702C and R702H mutations were only associated with FTNS, EPS, or
      APSM, thus defining a region of MYHIIA critical in the combined pathogenesis of
      macrothrombocytopenia, nephritis, and deafness. The E1841K, D1424N, and R1933X
      coiled-coil domain mutations were common to both MHA and FTNS. Haplotype analysis
      using three novel microsatellite markers revealed that three E1841K carriers--one
      with MHA and two with FTNS--shared a common haplotype around the MYH9 gene,
      suggesting a common ancestor. The two new globular-head mutations, K371N and
      R702H, as well as the recently identified MYH9 mutation, R705H, which results in
      DFNA17, were modeled on the basis of X-ray crystallographic data. Altogether, our
      data suggest that MHA, SBS, FTNS, EPS, and APSM comprise a phenotypic spectrum of
      disorders, all caused by MYH9 mutations. On the basis of our genetic analyses,
      the name "MYHIIA syndrome" is proposed to encompass all of these disorders.

PMID- 11590546
TI  - Excess of twins among affected sibling pairs with autism: implications for the
      etiology of autism.
AB  - It is widely accepted that genes play a role in the etiology of autism. Evidence
      for this derives, in part, from twin data. However, despite converging evidence
      from gene-mapping studies, aspects of the genetic contribution remain obscure. In
      a sample of families selected because each had exactly two affected sibs, we
      observed a remarkably high proportion of affected twin pairs, both MZ and DZ. Of
      166 affected sib pairs, 30 (12 MZ, 17 DZ, and 1 of unknown zygosity) were twin
      pairs. Deviation from expected values was statistically significant (P<10(-6) for
      all twins); in a similarly ascertained sample of individuals with type I
      diabetes, there was no deviation from expected values. We demonstrate that to
      ascribe the excess of twins with autism solely to ascertainment bias would
      require very large ascertainment factors; for example, affected twin pairs would
      need to be, on average, approximately 10 times more likely to be ascertained than
      affected non-twin sib pairs (or 7 times more likely if "stoppage" plays a role).
      Either risk factors (related to twinning or to fetal development) or other
      factors (genetic or nongenetic) in the parents may contribute to autism.

PMID- 11590547
TI  - The genetic dissection of complex traits in a founder population.
AB  - We estimated broad heritabilities (H(2)) and narrow heritabilities (h(2)) and
      conducted genomewide screens, using a novel association-based mapping approach
      for 20 quantitative trait loci (QTLs) among the Hutterites, a founder population
      that practices a communal lifestyle. Heritability estimates ranged from.21 for
      diastolic blood pressure (DBP) to.99 for whole-blood serotonin levels. Using a
      multipoint method to detect association under a recessive model we found evidence
      of major QTLs for six traits: low-density lipoprotein (LDL), triglycerides,
      lipoprotein (a) (Lp[a]), systolic blood pressure (SBP), serum cortisol, and whole
      blood serotonin. Second major QTLs for Lp(a) and for cortisol were identified
      using a single-point method to detect association under a general two-allele
      model. The heritabilities for these six traits ranged from.37 for triglycerides
      to.99 for serotonin, and three traits (LDL, SBP, and serotonin) had significant
      dominance variances (i.e., H(2) > h(2)). Surprisingly, there was little
      correlation between measures of heritability and the strength of association on a
      genomewide screen (P>.50), suggesting that heritability estimates per se do not
      identify phenotypes that are influenced by genes with major effects. The present
      study demonstrates the feasibility of genomewide association studies for QTL
      mapping. However, even in this young founder population that has extensive
      linkage disequilibrium, map densities <<5 cM may be required to detect all major
      QTLs.

PMID- 11590548
TI  - Markers for mapping by admixture linkage disequilibrium in African American and
      Hispanic populations.
AB  - Population linkage disequilibrium occurs as a consequence of mutation, selection,
      genetic drift, and population substructure produced by admixture of genetically
      distinct ethnic populations. African American and Hispanic ethnic groups have a
      history of significant gene flow among parent groups, which can be of value in
      affecting genome scans for disease-gene discovery in the case-control and
      transmission/disequilibrium test designs. Disease-gene discovery using mapping by
      admixture linkage disequilibrium (MALD) requires a map of polymorphic markers
      that differentiate between the founding populations, along with differences in
      disease-gene allele frequencies. We describe markers appropriate for MALD mapping
      by assessing allele frequencies of 744 short tandem repeats (STRs) in African
      Americans, Hispanics, European Americans, and Asians, by choosing STR markers
      that have large differences in composite delta, log-likelihood ratios, and/or
      I*(2) for MALD. Additional markers can be added to this MALD map by utilization
      of the rapidly growing single-nucleotide-polymorphism databases and the
      literature, to achieve a 3-10-cM scanning scale. The map will be useful for
      studies of diseases, including prostate and breast cancer, diabetes,
      hypertension, and end-stage renal disease, that have large differences in
      incidence between the founding populations of either Hispanics or African
      Americans.

PMID- 11590549
TI  - The importance of genealogy in determining genetic associations with complex
      traits.

PMID- 11590550
TI  - Reporting of linkage results.

PMID- 11590551
TI  - Examinations of methylenetetrahydrofolate reductase C677T and A1298C mutations-
      and in utero viability.

PMID- 11590553
TI  - The effect of estrogen replacement therapy on ventricular repolarization dynamics
      in healthy postmenopausal women.
AB  - Even though gender-specific differences in ventricular repolarization have gained
      wide recognition, the underlying mechanisms remain unknown. Because estrogen
      hormones may represent a causative factor for the changes in ventricular
      repolarization in women, this study evaluates a potential impact of estrogen
      replacement therapy on ventricular repolarization dynamics. Beat-to-beat QT and
      RR interval variability and QT/RR relationship during 5 minute resting high
      resolution electrocardiogram recordings were measured in 30 healthy
      postmenopausal women (mean age 54.5 years) before and after 10 weeks of estrogen
      replacement therapy (ERT) with estradiol 2 mg/day. The 2 control groups included
      12 healthy postmenopausal women of the similar age, who did not receive ERT, and
      11 comparably healthy age-matched men. To evaluate ventricular repolarization
      dynamics, QT/RR linear regression slopes were calculated. After the 10-week
      period, the QT/RR regression slope increased by 93% in the ERT group (P <.001),
      but no alterations were noted in either the male or female controls. The overall
      variability of RR and QT intervals did not change in any of the groups studied.
      Our results suggest that ERT causes alterations in ventricular repolarization
      dynamics without significantly affecting the autonomic nervous tone.

PMID- 11590554
TI  - Seasonal variability of the QT dispersion in healthy subjects.
AB  - We studied the seasonal variability of QT dispersion in 25 healthy subjects, aged
      36 +/- 5 (25 to 46) years. Four seasonal 12-lead rest electrocardiograms (ECGs)
      recorded at a double amplitude were performed at 25 mm/s at intervals of roughly
      3 months. To avoid possible confusion from the circadian rhythm of QT dispersion,
      subsequent ECGs were recorded within 30 minutes of the reference summer one. The
      QT dispersion was calculated as the difference between the longest and the
      shortest mean QT intervals. There was a seasonal variability in the QT dispersion
      (P =.001), with the largest QT dispersion occurring in winter (66 +/- 21 ms) and
      the smallest one in spring (48 +/- 18 ms). In conclusion, there exists a seasonal
      variability of QT dispersion in healthy subjects and such variability should be
      taken into consideration in comparison of the QT dispersion.

PMID- 11590555
TI  - Lack of noninvasive markers of ventricular repolarization inhomogeneity in
      patients with idiopathic ventricular tachyarrhythmia.
AB  - Noninvasive markers reflecting repolarization inhomogeneity have been proposed to
      be useful indices for identifying patients at risk of ventricular arrhythmias
      based on organic heart disease. In this study, we clarify whether or not
      repolarization inhomogeneity markers are useful in patients with idiopathic
      ventricular tachycardia (VT). We investigated T-wave alternans (TWA) and
      corrected QT-interval dispersion (QTD) in 84 consecutive patients with idiopathic
      VT, 90 patients with VT associated with organic heart disease (organic VT), and
      87 normal individuals. VT was defined as tachycardia lasting > or =5 consecutive
      ventricular ectopic beats at a rate of > or =120 beats/min. TWA was positive in
      20 of 84 patients (24%) with idiopathic VT, 59 of 90 patients (66%) with organic
      VT, and 16 of 87 normal individuals (18%). The alternans voltage was 2.6 +/- 3.1
      micro V in idiopathic VT patients, 5.6 +/- 6.4 micro V in organic VT patients,
      and 2.9 +/- 5.7 micro V in normal individuals. QTD were 53 +/- 20 ms in
      idiopathic VT patients, 92 +/- 20 ms in organic VT patients, 46 +/- 18 ms in
      normal individuals, respectively. A positive TWA test result was seen more (P
      <.01) frequently, and QTD was longer (P <.01) in organic VT patients compared to
      normal individuals, whereas there was no difference between idiopathic VT
      patients and normal individuals. In addition, in patients with idiopathic VT,
      neither did any of these measurements differ between patients with sustained VT
      (lasting for > or =30 s) and those with nonsustained VT. Noninvasive markers of
      repolarization inhomogeneity, such as TWA and QTD, are not useful for identifying
      patients with idiopathic VT. Repolarization inhomogeneity may not affect to the
      pathogenesis of idiopathic VT.

PMID- 11590556
TI  - Gender and atrioventricular conduction properties of patients with symptomatic
      atrioventricular nodal reentrant tachycardia and Wolff-Parkinson-White syndrome.
AB  - The objective of this study was to delineate the sex distribution and
      atrioventricular conduction properties in patients with manifest or concealed
      Wolff-Parkinson-White syndrome (WPW) and atrioventricular nodal reentrant
      tachycardia (AVNRT). The study comprised 328 patients with AVNRT, 347 with
      manifest, and 220 with concealed WPW who underwent radiofrequency ablation. A
      male preponderance was observed in patients with manifest WPW (69%), but not in
      those with concealed WPW (52%) and female preponderance in AVNRT patients (67%).
      The PR (166 +/- 25 ms) and AH (88 +/- 20 ms) intervals obtained 30 minutes after
      ablation in manifest WPW patients were significantly longer than in concealed WPW
      patients (149 +/- 20, 76 +/- 15 ms, P <.0001). The PR (146 +/- 20 ms) and AH
      intervals (75 +/- 15 ms) measured before ablation in AVNRT patients were shorter
      than those obtained before ablation in concealed WPW patients (154 +/- 21, 80 +/-
      17 ms, P <.05) and after ablation in manifest WPW patients (P <.0001). The PR
      interval in AVNRT patients was also shorter than those measured during follow-up
      in concealed (153 +/- 21 ms, P <.05) and manifest WPW patients (165 +/- 23 ms, P
      <.0001). The ventriculoatrial block cycle length in AVNRT patients was
      significantly shorter than in manifest and concealed WPW patients. When age
      matched patients were assigned to each group, significant differences in PR
      interval were observed between men and women (159 +/- 22 vs. 151 +/- 22 ms, P
      <.0001). Differences in sex distribution exist among patients with manifest and
      concealed WPW and AVNRT. The atrioventricular conduction properties required for
      the manifestation of pre-excitation and induction of AVNRT and gender differences
      in atrioventricular conduction may account for the differences in sex
      distribution.

PMID- 11590557
TI  - Ethnic differences in electrocardiographic intervals and axes.
AB  - The presence of ethnic differences in electrocardiographic (ECG) patterns is
      debated. We retrospectively examined the first 1,000 medical files of a multi
      ethnic community, where all individuals shared similar living conditions. Only
      healthy adults (ages 15 to 60 years) were included. All patients had similar
      socioeconomic, nutritional, environmental, and occupational conditions. Interval
      and axes measurements were obtained through integrated computerized analysis from
      a standard 12-lead ECG. ECGs from 597 patients were included in the study: 350
      Saudi Arabians, 95 Indians, 39 Jordanians, 17 Sri-Lankans, 39 Filipinos, and 57
      Caucasians; 349 patients were men. Interval and axes were compared by analysis of
      variance. No statistically significant differences were found among ethnic groups
      in PR interval, QRS duration, QT interval, P wave axis, QRS axis, or T wave axis
      in men (P =.05). In women, Jordanians had longer QRS duration than Filipinos
      (87.69 +/- 10.4, 78.81 +/- 5.47 ms, respectively, P =.014). P-wave axis was lower
      in Filipino women than Saudi, Indian, and Caucasian women (36.87 +/- 26.32, 50.39
      +/- 16.88, 52.23 +/- 16.67, 63.19 +/- 14.55 degrees, respectively, P =.002). QRS
      axis was significantly higher in Filipino than Saudi women (53.06 +/- 26.14,
      32.62 +/- 28.31 degrees, respectively, P <.014). There was no ethnic difference
      in ECG interval measurements in men. However, in women, there were differences in
      QRS interval, and P and QRS wave axes. Although women had a statistically
      significant difference in intervals, the magnitude was not clinically
      significant. Current reference standards for ECG intervals and axes can be used
      across the ethnic groups studied.

PMID- 11590558
TI  - Both right and left cervical cordotomies depress sympathetic indexes derived from
      heart rate variability in humans.
AB  - Unilateral percutaneous cervical cordotomy, performed in humans to relieve
      intractable cancer pain, elicits signs of ipsilateral sympathetic block. In
      patients undergoing right or left percutaneous cervical cordotomy (9 per group),
      changes in sympathovagal balance were evaluated by spectral analysis of heart
      rate to confirm the sympatholytic effect of this surgical procedure and to
      investigate the lateralization of sympathetic cardiac control. For these
      purposes, heart rate variability was recorded 1 hour before cordotomy and 24
      hours later. Cordotomy significantly depressed the low frequency peak (LF) of
      heart rate variability and increased the high frequency component (HF), when
      measured as a percentage of total power. As a consequence, the LF/HF ratio
      decreased significantly (P =.001), particularly during standing. The effects of
      right or left cordotomies were not significantly different. In conclusion, in
      humans unilateral percutaneous cervical cordotomy depresses some sympathetic
      indexes (LF/total power ratio and LF/HF ratio) derived from heart rate
      variability, irrespective of side.

PMID- 11590575
TI  - Acute myocardial injury caused presumably by coronary spasm after magnesium
      fluoro-silicate ingestion.
AB  - A patient who developed magnesium fluoro-silicate poisoning is described. This
      condition was manifest by the findings of acute chest pain, dysphagia, diarrhea,
      metabolic acidosis, hypocalcemia and hypomagnesemia and was complicated by acute
      myocardial injury-a phenomenon not previously described. Coronary cineangiography
      showed normal coronary arteries. The physiopathologic mechanisms of this
      electrocardiographic finding are discussed.

PMID- 11590576
TI  - A case of familial atrioventricular heart block affected by alteration of the
      autonomic nervous system.
AB  - Familial atrioventricular heart block affected by the autonomic nervous system
      has rarely been documented. We describe a 35-year-old man who had first-degree
      atrioventricular heart block with a PR interval of 0.46 s. He had a family
      history of 2 members with complete heart block and 1 with documented atrial
      standstill. The man's P-R interval was shortened by exercise and phenylephrine
      administration. In the electrophysiolgic study, a "split His" with an H-H' of 220
      ms was recognized. Such a case of familial atrioventricular heart block with
      abnormal His-Purkinje conduction affected by the autonomic nervous system is very
      rare and worthy of description.

PMID- 11590577
TI  - Aborted sudden death, transient Brugada pattern, and wide QRS dysrrhythmias after
      massive cocaine ingestion.
AB  - Although cocaine is one of the leading causes of drug-related deaths, there is
      little clinical information describing the precise sequence of events leading to
      death in the cocaine intoxication. Usually, cocaine-related sudden deaths are
      unwitnessed, its electrocardiographic features are not attainable, and the
      majority of these patients have a rapidly fatal course and die before arriving at
      the hospital. We report a patient with massive cocaine ingestion who developed
      psychomotor agitation and generalized seizures followed by asystolic cardiac
      arrest. Ventilation with supplemental oxygen by endotracheal intubation
      immediately restored spontaneous heart beat. After resuscitation, a severe
      metabolic acidosis (pH 6.65) and cardiac dysrrhythmias consistent with sodium
      channel poisoning were detected. The electrocardiogram showed accelerated
      junctional rhythm at 85 beats/min with right bundle branch block and left
      anterior hemiblock configuration, prolongation of QRS (0.16 sec) and QTc (0.52
      sec) intervals, and terminal J wave associated with coved ST-segment elevation in
      leads V(1) and V(2) resembling the Brugada syndrome. Sodium bicarbonate
      administration was quickly followed by normalization of the cardiac conduction
      disturbances. This article discusses the clinical and electrophysiologic
      implications of these findings.

PMID- 11590578
TI  - Advanced A-V block with apparent A-V junctional escape complexes because of dual
      A-V nodal pathways.
AB  - We report a patient with second degree A-V block in whom several sinus impulses
      were conducted over the slow A-V nodal pathway, resulting in P-R intervals so
      prolonged to suggest a diagnosis of intermittent advanced A-V block with A-V
      junctional escape complexes. However, the "escape" cycles were markedly
      irregular, and moreover, "escape" complexes often occurred with R-R cycles
      shorter than those ended by conducted sinus beats. These observations suggested
      that no escape mechanism was present. The marked variability of P-R intervals was
      a manifestation of dual A-V nodal pathways: short P-R intervals expressed
      conduction over the fast pathway, whereas long P-R intervals corresponded to
      sinus impulses conducted over the slow pathway.

PMID- 11590579
TI  - Some highlights in the emergence of modern concepts of osteoarthritis.
AB  - The present-day concept that osteoarthritis may be amenable to biological
      modification rather than a hopeless expression of old age or injury has
      historical roots in the period of 1935 through the early 1970s. One root was the
      structural and chemical delineation of the connective tissues: discovery of the
      proteoglycans and multiple molecular species of collagen. Another was the
      recognition of the ability of mature articular chondrocytes to replicate
      themselves rather than being terminally differentiated. A third was the
      elucidation of the engineering physiology of the joint: the role of matrix
      hydrophilia to the material properties of articular cartilage and biolubrication.
      Each root has direct relevance to ongoing therapeutic approaches to degenerative
      joint disease. The early epidemiological studies of Kellgren and Lawrence evolved
      into new techniques for testing their validity in clinical practice. Along the
      way there was a rich 2-way interaction between scientists and clinicians in
      arriving at these ideas.

PMID- 11590580
TI  - Popliteal cysts in adults: a review.
AB  - OBJECTIVE: To review the epidemiology, clinical presentation, pathogenesis,
      imaging, differential diagnosis, complications, and treatment of popliteal cysts.
      METHODS: References were taken from MEDLINE from 1985 to 1998 under the subject
      "Popliteal Cyst" with subheadings of Radiography, Ultrasonography, and
      Radionuclide Imaging. Other pertinent references were used. Childhood cysts were
      excluded. RESULTS: Depending on the studied population and the imaging technique,
      5% to 32% of knee problems may have these cysts, with 2 age-incidence peaks of 4
      to 7 years and 35 to 70 years. In older patients there is usually coexistent
      joint pathology. Symptoms may arise in the popliteal fossa from the cyst itself
      or be dominated by knee pain from coexisting knee pathology. Many cysts are
      asymptomatic. Physical examination will miss one half of these cysts.
      Pathogenesis depends on the connection between the joint and bursa, with a
      valvelike effect allowing passage of fluid from the joint into the bursa with
      subsequent distention producing these cysts. Some bursae have no such joint
      bursal communication, and the cysts arise primarily as bursitis of the
      gastrocnemio-semimembranosus bursa. Imaging is performed by plain x-ray,
      ultrasound, arthrography, computerized axial tomography, magnetic resonance
      imaging, or nuclear scan; sonography is the method of choice. Complicated cysts
      with extension or rupture into the calf mimic phlebitis, an important
      differential diagnosis. Asymptomatic cysts found incidentally need no treatment;
      most symptomatic cysts respond to intra-articular corticosteroid injections.
      Surgical excision is rarely necessary. CONCLUSIONS AND RELEVANCE: Popliteal cysts
      are fairly common, may not be found on physical examination, require imaging
      (preferably sonography) to be identified, mimic phlebitis when extending into the
      calf, and often respond to intra-articular steroid or, rarely, surgical
      resection.

PMID- 11590581
TI  - Systemic medium-sized vessel vasculitis associated with chronic myelomonocytic
      leukemia.
AB  - OBJECTIVE: To determine the clinical aspects of systemic vasculitis associated
      with chronic myelomonocytic leukemia (CMML). METHODS: In this retrospective
      study, 8 patients suffering from systemic vasculitis associated with CMML are
      described. The French and English literature on systemic vasculitis associated
      with myelodysplasia was reviewed. RESULTS: All 8 patients had a systemic medium
      sized vessel vasculitis which fulfilled the American College of Rheumatology
      criteria for polyarteritis nodosa in the setting of active CMML. Antineutrophil
      cytoplasmic antibodies (ANCA) were negative in 7 patients. One patient had
      cytoplasmic ANCA by indirect immunofluorescence without antiproteinase 3 or
      antimyeloperoxydase antibodies on the enzyme-linked immunosorbent assay. At
      presentation, 6 patients had fever of unknown origin, 5 had polymyalgia
      rheumatica, 3 had sensory hearing loss, and 4 had eosinophilia. None had viral
      infection or drug-associated vasculitis. Diagnostic procedures included renal or
      hepatic angiography in 6 patients which showed microaneurysms in 4, skin and
      temporal artery biopsy in 2 which showed vasculitis, and 1 postmortem examination
      which showed gastroduodenal arteritis. All patients were treated with
      corticosteroids, and 7 received immunosuppressive drugs. Death was attributable
      to vasculitis in 2 cases, infection in 3, and other vasculitis-related causes in
      2. In a review of the French-English literature, we found 11 similar cases of
      ANCA-negative systemic vasculitis, generally associated with refractory anemia,
      with or without blast excess. CONCLUSIONS: Systemic ANCA-negative polyarteritis
      nodosa-type vasculitis seems closely associated to CMML. Clinical presentation is
      nonspecific, and systemic vasculitis should be suspected when a patient with
      myelodysplasia develops atypical manifestations. Renal, gastrointestinal, or
      hepatic angiography are useful diagnostic procedures when more invasive biopsies
      should be avoided because of low platelet count. The prognosis of CMML-associated
      systemic vasculitis is poor.

PMID- 11590582
TI  - Catastrophic antiphospholipid syndrome: remission following leg amputation in 2
      cases.
AB  - OBJECTIVE: The antiphospholipid syndrome is characterized by venous and arterial
      thrombotic events that are often recurrent, thrombocytopenia, recurrent fetal
      loss, and elevated titers of antiphospholipid antibodies. A subtype of patients
      with a particularly overwhelming clinical picture has been termed catastrophic
      antiphospholipid syndrome (CAPS). In this report, we present 2 patients who
      exhibited a similar multisystem disorder associated with gangrenous changes in
      the lower extremities. METHODS: Two patients with CAPS are presented,
      highlighting the impact of this disorder on the patients and the response to
      various therapeutic modalities. RESULTS: Both patients had pulmonary, cardiac,
      cutaneous, and neurologic findings consistent with CAPS. In addition, they had
      large purulent leg ulcers associated with livedo reticularis. Amputation of the
      legs in each case induced remission of the systemic illness. CONCLUSIONS: We
      believe that infection plays a significant role in the pathogenesis and
      amplification of the antiphospholipid syndrome. In certain patients, this
      association probably is mediated via immune mechanisms, which also enhance the
      genesis of atherosclerosis. After the foci of infection (suppurative leg ulcers)
      were removed, the underlying illness improved. These case studies provide an
      opportunity to study the interrelationship between several confounding factors
      that converge and lead to the development of this autoimmune condition.

PMID- 11590583
TI  - Cotrimoxazole treatment for rheumatoid arthritis.
AB  - OBJECTIVES: To review the literature on the immunomodulatory and anti
      inflammatory properties of cotrimoxazole (CTX)-a combination of sulfamethoxazole
      and trimethoprim, to summarize the use of this medication in the treatment of
      autoimmune diseases, to stimulate and renew the interest of both physicians and
      researchers in this possible therapy for rheumatoid arthritis (RA), and to
      inspire further investigation in this field. METHODS: A MEDLINE search of the
      literature from 1966 until 2000 was performed, and information about the
      pharmacology of CTX and its use in the therapy of rheumatic diseases was
      critically reviewed. RESULTS: RA treatment is associated with numerous problems
      such as lack of efficacy, frequent side effects, and high cost. Analysis of the
      relevant literature revealed that experience with CTX in the treatment of RA is
      limited. However, the results of several nonrandomized and evidently forgotten
      clinical trials and laboratory investigations suggested that CTX might serve as
      an effective and inexpensive therapy for RA. Several lines of evidence suggested
      that CTX has nonspecific anti-inflammatory and immunomodulatory properties.
      Although nausea and vomiting were common reasons for CTX withdrawal, they were
      noted in only some studies, and no major organ toxicity was observed.
      CONCLUSIONS: Because of its therapeutic qualities, low cost, and relative
      nontoxicity, CTX seems to warrant a role in the treatment of RA.

PMID- 11590584
TI  - Middle Eocene primate tarsals from China: implications for haplorhine evolution.
AB  - We describe tarsal remains of primates recovered from the Middle Eocene
      (approximately 45 mya) Shanghuang fissures in southern Jiangsu Province, China.
      These tarsals document the existence of four higher-level taxa of haplorhine
      primates and at least two adapid species. The meager and poorly preserved adapid
      material exhibits some similarities to European adapines like Adapis. The
      haplorhine primates are divided into two major groups: a "prosimian group"
      consisting of Tarsiidae and an unnamed group that is anatomically similar to
      Omomyidae; and an "anthropoid group" consisting of Eosimiidae and an unnamed
      group of protoanthropoids. The anthropoid tarsals are morphologically
      transitional between omomyids (or primitive haplorhines) and extant
      telanthropoids, providing the first postcranial evidence for primates which
      bridge the prosimian-anthropoid gap. All of the haplorhines are extremely small
      (most are between 50-100 g), and the deposits contain the smallest euprimates
      ever documented. The uniqueness of this fauna is further highlighted by the fact
      that no modern primate community contains as many tiny primates as does the fauna
      from Shanghuang.

PMID- 11590585
TI  - In vivo function of the craniofacial haft: the interorbital "pillar".
AB  - The craniofacial haft resists forces generated in the face during feeding, but
      the importance of these forces for the form of the craniofacial haft remains to
      be determined. In vivo bone strain data were recorded from the medial orbital
      wall in an owl monkey (Aotus), rhesus macaques (Macaca mulatta), and a galago
      (Otolemur) during feeding. These data were used to determine whether: the
      interorbital region can be modeled as a simple beam under bending or shear; the
      face is twisting on the brain case during unilateral biting or mastication; the
      interorbital "pillar" is being axially compressed during incisor loading and both
      axially compressed and laterally bent during mastication; and the interorbital
      "pillar" transmits axial compressive forces from the toothrow to the braincase.
      The strain data reveal that the interorbital region cannot be modeled as a
      anteroposteriorly oriented beam bent superiorly in the sagittal plane during
      incision or mastication. The strain orientations recorded in the majority of
      experiments are concordant with those predicted for a short beam under shear,
      although the anthropoids displayed evidence of multiple loading regimes in the
      medial orbital wall. Strain orientation data corroborate the hypothesis that the
      strepsirrhine face is twisted during mastication. The hypothesis that the
      interorbital region is a member in a rigid frame subjected to axial compression
      during mastication receives some support. The hypothesis that the interorbital
      region is a member in a rigid frame subjected to lateral bending during
      mastication is supported by the epsilon1/absolute value epsilon2 ratio data but
      not by the strain orientation data. The timing of peak shear strains in the
      medial orbital wall of anthropoids does not bear a consistent relationship to the
      timing of peak shear strain in the mandibular corpus, suggesting that bite force
      is not the only external force influencing the medial orbital wall. Strain
      orientation data suggest the existence of two distinct loading regimes, possibly
      associated with masseter or medial pterygoid contraction. Regardless of the
      loading regime, all taxa showed low strain magnitudes in the medial orbital wall
      relative to the anterior root of the zygoma and the mandibular corpus. The strain
      gradients documented here and elsewhere suggest that, in anthropoids at least,
      local effects of external forces are more important than a single global loading
      regime. The low strain magnitudes in the medial orbital wall and in other thin
      bony plates around the orbit suggest that these structures are not optimally
      designed for resisting feeding forces. It is hypothesized that their function is
      to provide rigid support and protection for soft-tissue structures such as the
      nasal epithelium, the brain, meninges, and the eye and its adnexa. In contrast
      with the face of Otolemur, which appears to be subjected to a single predominant
      loading regime, anthropoids may experience different loading regimes in different
      parts of the face. This implies that the anthropoid and strepsirrhine facial
      skulls might be optimized for different functions.

PMID- 11590586
TI  - Evolution of dentition in prehistoric Ohio Valley Native Americans III. Metrics
      of deciduous dentition.
AB  - Deciduous tooth size in Native Americans of the Ohio Valley area is fairly stable
      from the terminal Late Archaic (3200 BP) through the Late Prehistoric (350 BP)
      periods. Some fluctuation in average size did occur during this time. These
      fluctuations most likely reflect random changes due to gene drift. However, no
      difference in the pattern of interactions among the sizes of teeth (covariance
      structures) can be demonstrated during this period. Principal components analysis
      of the buccolingual and mesiodistal dimensions in the total sample indicate that
      the major axis of deciduous tooth size in the Ohio Valley population shows an
      allometric relationship, with the dimensions of the anterior teeth increasing (or
      decreasing) as the 1.33 power of the dimension of m1(1) and as the 2.0 power of
      the dimension of m2(2). Comparison of the Ohio Valley samples with other samples
      from the Eastern Woodlands suggests that geography may have played a minor role
      in structuring deciduous tooth size variation. For the most part, however, widely
      separated Eastern Woodlands populations appear to have been evolving
      independently with respect to deciduous tooth size.

PMID- 11590587
TI  - Craniometric variation and the settlement of the Americas: testing hypotheses by
      means of R-matrix and matrix correlation analyses.
AB  - New archaeological findings and the incorporation of new South American skull
      samples have raised fundamental questions for the classical theories of the
      Americas' settlement. The aim of this study was to estimate craniometric
      variability among several Asian and Native American populations in order to test
      goodness of fit of the data to different models of ancient population entries and
      dispersions into the New World. Our data set includes Howells' variables recorded
      on East Asian, North American, and South American natives (except for Na-Dene
      speakers). Five Fuego-Patagonian samples and one Paleoamerican sample were also
      included. A multivariate extension of the R-matrix method for quantitative traits
      was used to obtain Fst values, which were considered estimations of intergroup
      variation. Three main models for the peopling of the New World were represented
      in hypothetical design matrices. Matrix permutation tests were performed to
      quantify the fit of the observed data with 1) geographical separation of the
      samples and 2) three ways of settlement, which were the Three Migration Model
      (TMM), the Single Wave Migration model (SWM), and the Two Components Settlement
      Model (TCS). R-matrix results showed high levels of heterogeneity among Native
      Americans. Matrix permutation analyses suggested that the model involving high
      Amerindian heterogeneity and two different morphological patterns or components
      (derived "Mongoloid" vs. generalized "non-Mongoloid") explains better the
      variation observed, even when the effects of geographical separation are removed.
      Whether these patterns arose as a result of two separate migration events or by
      local evolution from Paleoamericans to Amerindians remains unresolved.

PMID- 11590588
TI  - Variation in body mass index among Polish adults: effects of sex, age, birth
      cohort, and social class.
AB  - Variation in the body mass index (BMI) among occupationally active inhabitants of
      one Polish urban center was studied by means of a three-factor ANOVA. The
      material is cross-sectional and comprises 32,750 men and women aged 22-60 years,
      examined in five successive surveys between 1983-1999. The factors considered in
      each sex were: 1) age category, 2) year of examination, and 3) social class. The
      increase of BMI with age is markedly greater among women than among men. No
      sustained intergeneration trend towards increased BMI was detectable in either
      sex. The BMI means rise regularly with decreasing position on the social scale in
      both sexes, but this effect is much more dramatic in women. The latter finding
      suggests that the condition of being situated low on the social scale is
      conducive to growth of fatness with age, markedly more so in women than in men.
      The absence of a secular trend in BMI means during the period considered
      contrasts with results reported for a number of other countries. This finding is
      intriguing, because Poland underwent abrupt and profound socio-economic
      transformation in the early 1990s.

PMID- 11590589
TI  - Role of locomotor economy in the origin of bipedal posture and gait.

PMID- 11590590
TI  - Locomotor economy and the origin of bipedality: reply to Steudel-Numbers.

PMID- 11590591
TI  - Secretion by striated ducts of mammalian major salivary glands: review from an
      ultrastructural, functional, and evolutionary perspective.
AB  - In addition to their role in electrolyte homeostasis, striated ducts (SDs) in the
      major salivary glands of many mammalian species engage in secretion of organic
      products. This phenomenon usually is manifested as the presence of small serous
      like secretory granules in the apical cytoplasm of SD cells. The composition of
      these granules is largely unknown, except in the case of the cat and rat
      submandibular gland, where the granules have unequivocally been shown to contain
      kallikrein. In some species, the apical cytoplasm of SD cells contains variable
      numbers of vesicles, both spherical and elongated, that vary in appearance from
      'empty' to moderately dense. In the rat parotid gland, lucent vesicles transport
      glycoproteins to the luminal surface where they are incorporated into the apical
      plasmalemma and the glycocalyx. There is a strong possibility that in various
      species some of these vesicles are involved in transcytosis of antibodies to the
      saliva from their source (plasma cells) in the surrounding connective tissue. In
      addition, vesicles may engage in transfer of growth factors from the saliva to
      the interstitium. In a few species, conventional SDs have been replaced by ducts
      that are wholly given over to secretion, i.e., they entirely lack basal
      striations; although such ducts occupy the histological position of conventional
      SDs, it is not clear whether they represent a new type of duct or merely are
      modifications of SDs. Broad-based comparisons of ultrastructural and other data
      about SDs offer some insight into evolutionary history of salivary glands and
      their role in the adaptive radiation of mammals. Evolutionary patterns emerged
      when we made interspecific comparisons across mammalian orders. Among the bats,
      there is a clear relationship between SD secretion and general categories of
      diet.

PMID- 11590592
TI  - Cellular dynamics during evagination of the thyroid primordium in the chick
      embryo.
AB  - The thyroid forms as an outpouching of the ventral pharynx. Evidence supports the
      conclusion that formation of the thyroid pit is mediated by changes in the
      cytoskeleton that cause constriction of cell apices. However, it seems unlikely
      that a relatively flat epithelial sheet can be converted into a pit without
      either distortions of the surface or considerable rearrangement of cells to
      reduce surface area. Possible cellular rearrangements were investigated by
      tracing the movements of individual cells by using time-lapse video microscopy.
      Changes in shape of the primordium were investigated by marking with carbon and
      DiI and by scanning electron microscopy. Cell movements occurred only over short
      distances, mostly shifts relative to a neighbor, especially at the edge of the
      pit. Instead, cells rearranged into clusters that piled up at the edge of the pit
      and then tilted inside. Adjacent rings of pharyngeal cells were annexed by the
      growing thyroid, undergoing rearrangement into clusters, piling up at the edge,
      and moving inside the pit. The consequence was the formation of a series of shelf
      like extensions within the cavity, representing successive generations of cell
      rings moving inside. These results have implications for the formation of other
      organs by evagination.

PMID- 11590593
TI  - Comparative and functional anatomy of the mammalian lumbar spine.
AB  - As an essential organ of both weight bearing and locomotion, the spine is subject
      to the conflict of providing maximal stability while maintaining crucial
      mobility, in addition to maintaining the integrity of the neural structures.
      Comparative morphological adaptation of the lumbar spine of mammals, especially
      in respect to locomotion, has however received only limited scientific attention.
      Specialised features of the human lumbar spine, have therefore not been
      adequately highlighted through comparative anatomy. Mathematical averages were
      determined of 14 measurements taken on each lumbar vertebrae of ten mammalian
      species (human, chimpanzee, orang-utan, kangaroo, dolphin, seal, Przewalski's
      horse, cheetah, lama, ibex). The revealed traits are analysed with respect to the
      differing spinal loading patterns. All examined mammalian lumbar spines suggest
      an exact accommodation to specific biomechanical demands. The lumbar spine has
      reacted to flexion in a predominant plane with narrowing of the vertebral bodies
      in quadrupeds. Torsion of the lumbar spine is withstood by an increase in the
      transverse distance between the inferior articular processes in the upper lumbar
      spine in primates, but lower lumbar spine in humans, quadrupeds and the seal.
      Sagittal zygapophyseal joint areas resist torsion in the seal and humans. Ventral
      shear is resisted by frontal zygapophyseal joint areas in humans and primates,
      and dorsal shear by encompassing joints in the ibex. The human fifth lumbar
      vertebra is remarkable in possessing the largest endplate surface area and the
      widest distance between the inferior articular processes, as an indicator of the
      high degree of axial load and torsion in bipedalism.

PMID- 11590594
TI  - Autonomic innervation of the human cardiac conduction system: changes from
      infancy to senility--an immunohistochemical and histochemical analysis.
AB  - In order to study the changes in the pattern of autonomic innervation of the
      human cardiac conduction system in relation to age, the innervation of the
      conduction system of 24 human hearts (the age of the individuals ranged from
      newborn to 80 years), freshly obtained at autopsy, was evaluated by a combination
      of immunofluorescence and histochemical techniques. The pattern of distribution
      and density of nerves exhibiting immunoreactivity against protein gene product
      9.5 (PGP), a general neural marker, dopamine beta-hydroxylase (DBH) and tyrosine
      hydroxylase (TH), indicators for presumptive sympathetic neural tissue, and those
      demonstrating positive acetylcholinesterase (AChE) activity, were studied. All
      these nerves showed a similar pattern of distribution and developmental changes.
      The density of innervation, assessed semiquantitatively, was highest in the sinus
      node, and exhibited a decreasing gradient through the atrioventricular node,
      penetrating and branching bundle, to the bundle branches. Other than a paucity of
      those showing AChE activity, nerves were present in substantial quantities in
      infancy. They then increased in density to a maximum in childhood, at which time
      the adult pattern was achieved and then gradually decreased in density in the
      elders to a level similar to or slightly less than that in infancy. In contrast,
      only scattered AChE-positive nerves were found in the sinus and atrioventricular
      nodes, but were absent from the bundle branches of the infant heart, whereas
      these conduction tissues themselves possessing a substantial amount of
      pseudocholinesterase. During maturation into adulthood, however, the conduction
      tissues gradually lost their content of pseudocholinesterase but acquired a rich
      supply of AChE-positive nerves, comparable in density to those of DBH and TH
      nerves. The decline in density of AChE-positive nerves in the conduction tissues
      in the elders was also similar to those of DBH and TH nerves. Our findings of
      initial sympathetic dominance in the neural supply to the human cardiac
      conduction system in infancy, and its gradual transition into a sympathetic and
      parasympathetic codominance in adulthood, correlate well with the physiologic
      alterations known to occur in cardiac rate during postnatal development. The
      finding of reduction in density of innervation of the conduction tissue with
      ageing is also in agreement with clinical and electrophysiological findings such
      as age-associated reduction in cardiac response to parasympathetic stimulation.
      Finally, our findings also support the hypothesis that, in addition to the para
      arterial route, the parafascicular route of extension along the conduction tissue
      constitutes another pathway for the innervation of the conduction system of the
      human heart during development.

PMID- 11590595
TI  - The spatiotemporal relationship among Schwann cells, axons and postsynaptic
      acetylcholine receptor regions during muscle reinnervation in aged rats.
AB  - To morphologically define the aging-related features during muscle reinnervation
      the spatiotemporal relationships among the major components of the neuromuscular
      junctions (NMJs) were investigated. A total of 64 rats, 30 adults (4 months old)
      and 34 aged adults (24 months old), were used. Between 1 and 12 weeks after
      sciatic nerve-crushing injury, cryosections of skeletal muscle were single or
      double labeled for S100, a marker of Schwann cells (SCs), for protein gene
      product 9.5, a neuronal marker, and for alpha-bungarotoxin (alpha-BT), a marker
      of the acetylcholine receptor site (AChR site), and then observed by confocal
      laser microscopy. The most obvious age changes were noted: (1) the regenerating
      SCs and axons were delayed in their arrival at the NMJ, (2) the dimensions of
      terminal SCs and AChR sites displayed a drastic and long-lasting drop (for
      terminal SCs, during 1-8 weeks; for AChR sites, during 1-12 weeks); (3) the
      degree of spatial overlap between AChR sites and terminal SCs was markedly low
      until 8 weeks post-crush; (4) damage and poor formation in the SCs, terminal
      axons and AChR sites, together with poor process extension from the terminal SC
      or terminal axon, were pronounced; (5) persistent aberrant changes, such as
      multiple innervation and terminal axon sprouting, together with poorly formed
      collateral innervation, nerve bundles, and NMJs, more frequently occurred in the
      later reinnervation period. Thus, with aging, regeneration is impaired during the
      period in which regenerating SC strands and axons extend into NMJs and the
      subsequent establishment of nerve-muscle contact is in progress. A complex set of
      morphological abnormalities between or among the TSCs, terminal axons, and AChR
      sites may be important in slowing of regeneration and reinnervation in aged motor
      endplates.

PMID- 11590596
TI  - Interrelations of myogenic response, progressive atrophy of muscle fibers, and
      cell death in denervated skeletal muscle.
AB  - Little is known concerning the time-course and structural dynamics of
      reactivation of compensatory myogenesis in denervated muscle, its initiating
      cellular mechanisms, and the relationship between this process and the
      progression of postdenervation atrophy. The purpose of this study was to
      investigate the interrelations between temporal and spatial patterns of the
      myogenic response in denervated muscle and progressive atrophy of muscle fibers.
      Another objective was to study whether reactivation of myogenesis correlates with
      destabilization of the differentiated state and death of denervated muscle cells.
      It has remained unclear whether muscle fiber atrophy was the primary factor
      activating the myogenic response, what levels of cellular atrophy were associated
      with its activation, and whether the initiation and intensity of myogenesis
      depended on the local and individual heterogeneity of atrophic changes among
      fibers. For this reason, our objective was also to identify the levels of
      atrophic and degenerative changes in denervated muscle fibers that are correlated
      with activation of the myogenic response. We found that the reactivation of
      myogenesis in the tibialis anterior and extensor digitorum longus muscles of the
      rat starts between days 10-21 following nerve transection, before atrophy has
      attained advanced level, long before dead cells are found in the tissue.
      Formation of new muscle fibers reaches its maximum between 2 and 4 months
      following denervation and gradually decreases with progressive postdenervation
      atrophy. The myogenic response is biphasic and includes two distinct processes.
      The first process resembles the formation of secondary and tertiary generations
      of myotubes during normal muscle development and dominates during the first 2
      months of denervation. During this period, activated satellite cells form new
      myotubes on live differentiated muscle fibers. Most of the daughter myotubes in 1
      and 2-month denervated muscle develop on the surface of fast type parent muscle
      fibers, and some of the newly formed muscle fibers express slow myosin. Some fast
      type parent fibers are weakly or, more rarely, moderately immunopositive for
      embryonic isomyosin. This indicates that reactivation of myogenesis may also
      depend on the fiber type. The level of atrophy, destabilization of the
      differentiated myofiber phenotype, and degenerative changes of individual fibers
      in denervated muscle are very heterogeneous. The myogenic response of the first
      type is associated predominantly with fibers of average and higher than average
      levels of atrophy. Muscle cells that undergo a lesser degree of atrophy also form
      daughter fibers, although with a lower incidence. We did not find any correlation
      between the size of newly formed fibers and the level of atrophy of parent
      fibers. The topographical distribution of new myotubes both in the peripheral and
      central areas of the mid-belly equatorial sections at the early stages following
      nerve transection indicates that myogenesis of the first type represents a
      systemic reaction of muscle to the loss of neural control. These data indicate
      that activation of the myogenic response does not depend on cell death and
      degenerative processes per se. The second type of myogenesis is a typical
      regenerative reaction that occurs mainly within the spaces surrounded by the
      basal laminae of dead muscle fibers. Myocytes of different sizes are susceptible
      to degeneration and death, which indicates that cell death in denervated muscle
      does not correlate with levels of muscle cell atrophy. The regenerative process
      frequently results in development of abnormal muscle cells that branch or form
      small clusters. Replacement of lost fibers becomes activated between 2 and 4
      months following nerve transection, i.e., mainly at advanced stages of
      postdenervation atrophy, when cell death becomes a contributing factor of the
      atrophic process. In long-term denervated muscle, the first and second types of
      myogenesisoccur concurrently, and the topographical distribution of the myogenic
      response becomes more heterogeneous than during the first weeks following
      denervation. Thus, our data demonstrate differential temporal and spatial
      expression of two patterns of myogenesis in denervated muscle that appear to be
      controlled by different regulatory mechanisms during the postdenervation period.
      (c) 2001 Wiley-Liss, Inc.

PMID- 11590597
TI  - Spatial distribution of cell adhesion molecules on the peritoneal surface in the
      cecal perforation-induced peritonitis.
AB  - For understanding the immunological functions of the peritoneum, spatial
      localization of integrins and their ligands was studied by immuno-SEM on the
      peritoneal surface of mice with cecal perforation-induced peritonitis. The cecal
      peritoneum 24 hr after perforation was stained with specific antibodies against
      LFA-1, Mac-1, VLA-4, ICAM-1, VCAM-1, and fibronectin diluted with cold University
      of Wisconsin (UW) solution in conjunction with immuno-gold labeling. The spatial
      localization of those cell adhesion molecules was detected by backscatter
      electron (BSE) imaging with field emission scanning electron microscope (FESEM).
      Numerous leukocytes with diverse surface ultrastructure were observed on the
      peritoneal surface by FESEM. Some leukocytes were in contact with mesothelial
      cells, and others adhered to the exposed underlying connective tissue. The BSE
      imaging showed the ubiquitous distribution of Mac-1 on all membrane domains of
      leukocytes, i.e., cell body, ruffles, and microvilli. In contrast, predominant
      expressions of LFA-1 and VLA-4 were discernible on ruffles/microvilli of some
      leukocytes. The mesothelial cells remaining in the inflamed area expressed both
      ICAM-1 and VCAM-1 on their microvilli. The fibronectin was detected on presumable
      collagen fibers and/or fibrin over the exposed smooth muscle layer as well as on
      fibrin extending between leukocyte aggregation. The spatial microlocalization of
      integrins was clarified on the leukocytes emigrated in peritonitis, and their
      ligands were detected on the inflamed peritoneum.

PMID- 11590598
TI  - Expression of recombinant human acetylcholinesterase in transgenic tomato plants.
AB  - Enzyme therapy for the prevention and treatment of organophosphate poisoning
      depends on the availability of large amounts of cholinesterases. Transgenic
      plants are being evaluated for their efficiency and cost-effectiveness as a
      system for the bioproduction of therapeutically valuable proteins. Here we report
      production of a recombinant isoform of human acetylcholinesterase in transgenic
      tomato plants. Active and stable acetylcholinesterase, which retains the kinetic
      characteristics of the human enzyme, accumulated in tomato plants. High levels of
      specific activity were registered in leaves (up to 25 nmol min(-1) mg protein(
      1)) and fruits (up to 250 nmol min(-1) mg protein(-1)).

PMID- 11590599
TI  - Estimation of steady-state culture characteristics during acceleration-stats with
      yeasts.
AB  - Steady-state culture characteristics are usually determined in chemostat
      cultivations, which are very time-consuming. In contrast, acceleration-stat (A
      stat) cultivations in which the dilution rate is continuously changed with a
      constant acceleration rate are not so time-consuming, especially at high
      acceleration rates. Therefore, the A-stat could be advantageous to use instead of
      the chemostat. However, the highest acceleration rate, meaning the fastest A-stat
      that can be applied for estimating steady-state culture characteristics, is not
      known yet. Experimental results obtained with Zygosaccharomyces rouxii, an
      important yeast in soy sauce processes, showed that the culture characteristics
      during the A-stat with an acceleration rate of 0.001 h(-2) were roughly
      comparable to those of the chemostat. For higher acceleration rates the deviation
      between the culture characteristics in the A-stat and those in the chemostat
      obtained at the same dilution rate generally started to increase. The source of
      these deviations was examined by simulation for Saccharomyces cerevisiae. The
      simulations demonstrated that this deviation was not only dependent on the
      metabolic adaptation rate of the yeast, but also on the rate of change in
      environmental substrate concentrations during A-stats. From this work, it was
      concluded that an A-stat with an acceleration rate of 0.001 h(-2) is attractive
      to be used instead of chemostat whenever a rough estimation of steady-state
      culture characteristics is acceptable.

PMID- 11590600
TI  - Reactor optimization for alpha-1,2 glucooligosaccharide synthesis by immobilized
      dextransucrase.
AB  - The immobilization of dextransucrase in Ca-alginate beads relies on the close
      association between dextran polymer and dextransucrase. However, high amounts of
      dextran in the enzyme preparation drastically limit the specific activity of the
      immobilized enzyme (4 U/mL of alginate beads). Moreover, even in the absence of
      diffusion limitation at the batch conditions used, the enzyme behavior is
      modified by entrapment so that the dextran yield increases and the alpha-1,2
      glucooligosaccharides (GOS) are produced with a lower yield (46.6% instead of
      56.7%) and have a lower mean degree of polymerization than with the free
      dextransucrase. When the immobilized catalyst is used in a continuous reaction,
      the reactor flow rate necessary to obtain high conversion of the substrates is
      very low, leading to external diffusion resistance. As a result, dextran
      synthesis is even higher than in the batch reaction, and its accumulation within
      the alginate beads limits the operational stability of the catalyst and decreases
      glucooligosaccharide yield and productivity. This effect can be limited by using
      reactor columns with length to diameter ratio > or =20, and by optimizing the
      substrate concentrations in the feed solution: the best productivity obtained was
      3.74 g. U(-1). h(-1), with an alpha-1,2 GOS yield of 36%.

PMID- 11590601
TI  - Analysis of an engineered sulfate reduction pathway and cadmium precipitation on
      the cell surface.
AB  - We previously have genetically engineered an aerobic sulfate reduction pathway in
      Escherichia coli for the generation of hydrogen sulfide and demonstrated the
      pathway's utility in the precipitation of cadmium. To engineer the pathway, the
      assimilatory sulfate reduction pathway was modified so that cysteine was
      overproduced. Excess cysteine was then converted by cysteine desulfhydrase to an
      abundance of hydrogen sulfide, which then reacted with aqueous cadmium to form
      cadmium sulfide. In this study, observations of various E. coli clones were
      combined with an analysis of kinetic and transport phenomena. This analysis
      revealed that cysteine production is the rate-limiting step in the engineered
      pathway and provided an explanation for the phenomenon of cell surface
      precipitation. An analytical model showed that cadmium sulfide must form at the
      cell surface because the rate of cadmium sulfide formation is extremely fast and
      the rate of sulfide transport is relatively slow.

PMID- 11590602
TI  - Quantification of random motility and chemotaxis bacterial transport coefficients
      using individual-cell and population-scale assays.
AB  - A number of individual-cell and population-scale assays have been introduced to
      quantify bacterial motility and chemotaxis. The transport coefficients reported
      in the literature, however, span several orders of magnitude, making it difficult
      to ascertain to what degree variations in bacterial species/strain, growth
      medium, growth and experimental conditions, and experiment type contribute to the
      reported differences in coefficient values. We quantified the random motility of
      Escherichia coli AW405 using the capillary assay, stopped-flow diffusion chamber
      (SFDC), and tracking microscope. We obtained good agreement for the random
      motility coefficient between these assays when using the same bacterial strain
      and consistent growth and experimental conditions. Chemotaxis of E. coli toward
      the attractant alpha-methylaspartate was quantified using the SFDC and capillary
      assay. Good agreement for the chemotactic sensitivity coefficient between the
      SFDC and the capillary assay was obtained across a limited attractant
      concentration range. Three different mathematical models were considered for
      analyzing capillary assay data to obtain a chemotactic sensitivity coefficient.
      These models differed by their treatment of the bacterial concentration in the
      chamber and the attractant concentration at the mouth. Results from our study
      indicate that the capillary assay, the most commonly used bacterial random
      motility and chemotaxis assay, can be used to accurately quantify bacterial
      transport coefficients over a limited range of attractant concentrations,
      provided experiments are performed carefully and appropriate mathematical models
      are used to interpret the experimental data.

PMID- 11590603
TI  - Multiple stable states and hysteresis in continuous, oscillating cultures of
      budding yeast.
AB  - The conditions that precede the onset of autonomous oscillations in continuous
      yeast cultures were studied in three different types of experiments. It was found
      that the final state of the culture depended on the protocol used to start up the
      reactor. Batch cultures, switched to continuous operation at different stages of
      the batch growth curve, all exhibited similar dynamics-ethanol depletion followed
      by autonomous oscillations. Small perturbations of the distribution of states in
      the reactor, achieved by addition of externally grown cells, were able to quench
      the oscillatory dynamics. Reaching the desired operating point by slow dilution
      rate changes gave rise to different final states, two oscillatory states and one
      steady state, depending on the rate of change in dilution rate. The multiplicity
      of stable states at a single operating point is not explained by any current
      distributed model and points toward a segregated mechanism of these oscillations.

PMID- 11590604
TI  - Decolorization of reactive dyes by the white rot fungus Trametes versicolor in
      sequencing batch reactors.
AB  - The white rot fungus Trametes versicolor was shown to be capable of decolorizing
      three reactive dyes in a sequencing batch process, using glucose as the carbon
      and energy source over an extended period without supplementation of new
      mycelium. Decolorization activity was related to the expression of extracellular
      peroxidases and could be continuously reactivated by sheering the suspended
      pellets. Pure culture experiments were carried out simultaneously in agitated
      Erlenmeyer flasks and in completely stirred tank reactors with two azo dyes, C.I.
      Reactive Black 5 and C.I. Reactive Red 198 as well as the anthraquinone dye C.I.
      Reactive Blue 19 (Brilliant Blue R). Results show high and stable degrees of
      decolorization of 91%-99% in both systems, which could be repeated without
      decrease in activity over time. Under nonsterile conditions only five cycles of
      decolorization could be achieved. An increasing bacterial population suppressed
      fungal growth and the formation of peroxidases.

PMID- 11590605
TI  - Galactomannanases Man2 and Man5 from Thermotoga species: growth physiology on
      galactomannans, gene sequence analysis, and biochemical properties of recombinant
      enzymes.
AB  - The enzymatic hydrolysis of mannan-based hemicelluloses is technologically
      important for applications ranging from pulp and paper processing to food
      processing to gas and oil well stimulation. In many cases, thermostability and
      activity at elevated temperatures can be advantageous. To this end, the genes
      encoding beta-mannosidase (man2) and beta-mannanase (man5) from the
      hyperthermophilic bacteria Thermotoga neapolitana 5068 and Thermotoga maritima
      were isolated, cloned, and expressed in Escherichia coli. The amino acid
      sequences for the mannosidases from these organisms were 77% identical and
      corresponded to proteins with an M(r) of approximately 92 kDa. The translated
      nucleotide sequences for the beta-mannanase genes (man5) encoded polypeptides
      with an M(r) of 76 kDa that exhibited 84% amino acid sequence identity. The
      recombinant versions of Man2 and Man5 had similar respective biochemical and
      biophysical properties, which were also comparable to those determined for the
      native versions of these enzymes in T. neapolitana. The optimal temperature and
      pH for the recombinant Man2 and Man5 from both organisms were approximately 90
      degrees C and 7.0, respectively. The presence of Man2 and Man5 in these two
      Thermotoga species indicates that galactomannan is a potential growth substrate.
      This was supported by the fact that beta-mannanase and beta-mannosidase
      activities were significantly stimulated when T. neapolitana was grown on guar or
      carob galactomannan. Maximum cell densities increased by at least tenfold when
      either guar or carob galactomannan was added to the growth medium. For T.
      neapolitana grown on guar at 83 degrees C, Man5 was secreted into the culture
      media, whereas Man2 was intracellular. These localizations were consistent with
      the presence and lack of signal peptides for Man5 and Man2, respectively. The
      identification of the galactomannan-degrading enzymes in these Thermotoga species
      adds to the list of biotechnologically important hemicellulases produced by
      members of this hyperthermophilic genera.

PMID- 11590606
TI  - Statistical reconciliation of the elemental and molecular biomass composition of
      Saccharomyces cerevisiae.
AB  - A systematic mathematical procedure capable of detecting the presence of a gross
      error in the measurements and of reconciling connected data sets by using the
      maximum likelihood principle is applied to the biomass composition data of yeast.
      The biomass composition of Saccharomyces cerevisiae grown in a chemostat under
      glucose limitation was analyzed for its elemental and for its molecular
      composition. Both descriptions initially resulted in conflicting results
      concerning the elemental composition, molecular weight, and degrees of reduction.
      The application of the statistical reconciliation method, based on elemental
      balances and equality relations, is used to obtain a consistent biomass
      composition. Simultaneously, the error margins of the data sets are significantly
      reduced in the reconciliation process. On the basis of statistical analysis it
      was found that inclusion of about 4% water in the list of biomass constituents is
      essential to adequately describe the dry biomass and match both set of
      measurements. The reconciled carbon content of the biomass varied 4% from the
      ones obtained from the molecular analysis. The proposed method increases the
      accuracy of biomass composition data of its elements and its molecules by
      providing a best estimate based on all available data and thus provides an
      improved and consistent basis for metabolic flux analysis as well as black box
      modeling approaches.

PMID- 11590607
TI  - On-line stoichiometry and identification of metabolic state under dynamic process
      conditions.
AB  - A method for the on-line calculation of conversion rates and yield coefficients
      under dynamic process conditions was developed. The method is based on cumulated
      mass balances using a moving average method. Elemental balances were used to test
      the measured cumulated quantities for gross errors and inappropriate
      stoichiometry definition followed by data reconciliation and estimation of non
      measured conversion rates, using a bioprocess set-up including multiple on-line
      analysis techniques. The quantitative potential of the proposed method is
      demonstrated by executing transient experiments in aerobic cultures of
      Saccharomyces cerevisiae on glucose. Rates and yield coefficients could be
      consistently quantified in shift-up, shift-down, and accelerostat experiments.
      The method shows the capability to describe quantitatively transient changes in
      metabolism including uncoupling of catabolism and anabolism, also for the case
      when multiple components of metabolism are not measured. The validity of the
      experiment can be evaluated on-line. Additionally, the method detects with high
      sensitivity inappropriate stoichiometry definition, such as a change in state of
      metabolism. It was shown that concentration values can be misleading for the
      identification of the metabolic state. In contrast, the proposed method provides
      a clear picture of the metabolic state and new physiological regulations could be
      revealed. Hence, the novelty of the proposed method is the on-line availability
      of consistent stoichiometric coefficients allowing a significant speed up in
      strain characterization and bioprocess development using minimal knowledge of the
      metabolism. Additionally, it opens up the use of transient experiments for
      physiological studies.

PMID- 11590608
TI  - Automatic inducer addition and harvesting of recombinant Escherichia coli
      cultures based on indirect on-line estimation of biomass concentration and
      specific growth rate.
AB  - This article describes a novel bioreactor configuration for production
      optimization of recombinant proteins in Escherichia coli. Inducer addition and
      harvesting are controlled on-line based on indirect estimation of biomass
      concentration and specific growth rate from addition of NaOH to maintain constant
      pH. When either a predetermined biomass concentration is reached or the cultures
      have obtained, a constant specific growth rate inducer is introduced
      automatically. The induction period is ended by automatic harvesting of the
      cultures either at a predetermined biomass concentration or when substrate (in
      this study glucose) is depleted, detected as an increase of pH, or dissolved
      oxygen tension. During harvesting, metabolic activities are quenched within 3 min
      by cooling of the cell suspension. The system has been used to optimize
      expression of glutathione S-transferase (GST) fusion protein of the ligand
      binding domain of mouse peroxisome proliferator-activated receptor, GST-PPARalpha
      LBD. Total yield of GST-PPARalpha LBD was independent of the time of inducer
      addition as long as the length of induction period corresponded to at least 0.25
      cell divisions while the yield of soluble GST-PPARalpha LBD, the only active
      form, increased with the length of induction period. Highest yields were obtained
      when the inducer was added at low cell concentration as soon as constant specific
      growth rate was detected, resulting in induction periods corresponding to 3.4 +/-
      0.4 cell divisions. The specific growth rate remained almost constant for one
      cell division after inducer addition, whereafter it decreased. No decrease of
      specific growth rate was observed when inducer was added in the lag-phase, and no
      soluble protein was produced. These results suggest that solely soluble GST
      PPARalpha LBD acts as a growth inhibitor and that GST-PPARalpha LBD is expressed
      predominantly as inclusion bodies immediately after inducer addition whereas the
      proportion expressed as soluble protein is increased after 1 h of induction.
      Compared to the procedures, which are generally used for protein expression in
      the laboratory, this system is less labor intensive, it automatically provides
      recording of biomass concentration and specific growth rate, and it allows direct
      comparisons between expression of different proteins and performance of different
      constructs since the induction period is linked to growth.

PMID- 11590609
TI  - In vitro degradation of a polymeric dye (Poly R-478) by manganese peroxidase.
AB  - The aim of this study is the evaluation of the enzymatic action of the
      ligninolytic enzyme manganese peroxidase (MnP), through a suitable addition of
      H(2)O(2), as a feasible system for the in vitro degradation of complex
      structures. For this purpose, a highly recalcitrant polymeric dye (Poly R-478)
      was selected as a model compound. An amperometric technique was used to determine
      the H(2)O(2) requirement in the decolorization by nonpurified MnP. Two H(2)O(2)
      supply strategies-fed-batch (every hour) or semicontinuous (every 5 min)-were
      applied. The addition of H(2)O(2) in pulses led to a limited decolorization after
      the pulses and the instantaneous consumption or decomposition of H(2)O(2).
      Therefore, this way of addition may limit the actual H(2)O(2) concentration in
      the reaction mixture. In contrast, the semicontinuous strategy maintained lower
      and prolonged concentrations of H(2)O(2), which allowed a clearly greater
      decolorization (48% after 2 h). In addition, the effect of Mn(+2) concentration
      on the decolorization efficiency was investigated to establish the optimal
      application of the MnP-oxidative system. The enzymatic treatment provoked not
      only the destruction of the chromophoric groups but also a noticeable breakdown
      of the chemical structure of the dye. In experiments with pure enzyme, MnP proved
      to be the main factor responsible for the dye decolorization.

PMID- 11590610
TI  - Surface transformation of bioactive glass in bioreactors simulating microgravity
      conditions. Part I: experimental study.
AB  - Surface modified bioactive glass with surface properties akin to those of the
      bone mineral phase is an attractive candidate for use as a microcarrier material
      for 3-D growth of bone-like tissue in rotating wall vessel bioreactors (RWVs).
      The critical surface properties of this material are the result of reaction in
      solution. Because an RWV environment is completely different from conditions
      previously employed for bioactive glass testing, a detailed study of the surface
      reactions is warranted. Under properly chosen conditions, RWVs can also provide a
      simulated microgravity environment for the bioactive glass (BG) particles. In
      this sense, this study is also a report on the behavior of a bioactive material
      under microgravity conditions simulated on earth. A high aspect ratio vessel
      (HARV) and carefully selected experimental conditions enabled the simulation of
      microgravity in our laboratory. A complimentary numerical study was
      simultaneously conducted to ascertain the appropriateness of the experimental
      parameters (particle size, particle density, medium density, medium viscosity,
      and rotational speed) that ensure simulated microgravity conditions for the glass
      particles in the HARV. Physiological solutions (pH 7.4) with and without
      electrolytes, and also with serum proteins, were used to study the change in
      surface character resulting from simulated microgravity. Control tests at normal
      gravity, both static and dynamic, were also conducted. Solution and surface
      analyses revealed major effects of simulated microgravity. The rates of leaching
      of constituent ions (Si-, Ca-, and P-ions) were greatly increased in all
      solutions tested. The enhanced dissolution was followed by the enhanced formation
      of bone-like minerals at the BG surface. This enhancement is expected to affect
      adsorption of serum proteins and attachment molecules, which, in turn, may
      favorably affect bone cell adhesion and function. The findings of the study are
      important for the use of bioactive materials as microcarriers to generate and
      analyze 3-D bone-like tissue structures in bioreactors under microgravity
      conditions or otherwise.

PMID- 11590611
TI  - Surface transformation of bioactive glass in bioreactors simulating microgravity
      conditions. Part II: numerical simulations.
AB  - The effects of simulated microgravity on the surface modification of bioactive
      glass (BG) in solution were studied using a numerical method. Models were
      developed for estimating the mass transfers of different chemical species from
      the surface of bioactive glass particles (microcarriers) suspended in the
      rotating liquid medium of a NASA-designed high aspect ratio vessel (HARV)
      bioreactor and on the bottom surface of a static vial. The concentration profiles
      resulting from chemical reactions and ionic transports were ascertained.
      Numerical results for the transport under simulated microgravity in the HARV and
      at normal gravity in the static vial were compared. These results were also
      compared with those of experiments to verify the enhancement of the reaction
      kinetics under simulated microgravity conditions. The experimental and numerical
      studies confirm that simulated microgravity conditions lead to the quick
      achievement of bioactive glass surface modification.

PMID- 11590612
TI  - Introduction: Integrating health psychology into clinical practice.

PMID- 11590613
TI  - Psychotherapy for health and lifestyle change.
AB  - Health practitioners use various models for facilitating health or lifestyle
      change, which entails either stopping an unhealthy behavior or promoting a new
      healthy behavior. Four models offer evidence-based, systematic, and integrative
      approaches to lifestyle change. They are: the Transtheoretical Model or Stages of
      Change; Brief Motivational Interviewing; Prevention Oriented Primary Care; and
      the ECBIS Psychotherapy Model (Emotion, Cognition, Behavioral, Interpersonal, and
      System). This article reviews each model and features a case illustration to
      demonstrate how these models can be integrated and applied clinically to help a
      patient change multiple health behaviors.

PMID- 11590614
TI  - Treating chronic-pain patients in psychotherapy.
AB  - This article provides an overview of the breadth of issues a therapist may face
      in treating a person with chronic pain. Questions such as the relative
      contributions of biological and psychosocial influences on the patient's reported
      condition must be addressed. In addition, the counselor often must help the
      patient deal with psychopathology that occurs in reaction to the pain, which is
      likely to be contributing to it. Other financial, medical, and legal
      circumstances also may impinge on the therapeutic framework to limit or influence
      the course of treatment. Two examples of treatment lessons are offered, and a
      case example illustrates the lengthy and multidimensional course some treatments
      can take.

PMID- 11590615
TI  - Exercise in treating depression: broadening the psychotherapist's role.
AB  - Research findings over the past two decades strongly indicate that moderate
      exercise can have a beneficial effect upon depression, yet suggestions to
      depressed patients that they exercise rarely are followed. Despite the research,
      few psychotherapists employ exercise promotion and maintenance as part of their
      treatment. An approach to integrating exercise promotion into psychotherapy
      treatment is presented. It incorporates a therapist-patient collaborative process
      involving joint assessment of biopsychosocial barriers and facilitators for
      exercise initiation and maintenance that are unique to the patient. Based upon
      the assessment, a collaborative exercise plan is developed and implemented.

PMID- 11590616
TI  - Altering women's relationships with food: a relational, developmental approach.
AB  - Eating disorders, ranging from body-image distortions to full-blown anorexia
      nervosa and bulimia nervosa, reflect developmental issues and significant
      deficits in feelings of self-efficacy. The relational model, an outgrowth of
      theoretical work specific to the psychology of women, is an appropriate treatment
      approach. This model appreciates the social context and pressures that foster
      disconnection from the self and helps the woman to reconnect with self and
      others, decreasing the need for obsessive control over food and weight. Treatment
      emphasizes empathy, connection, mutuality, and authenticity and views
      disconnections and disruptions as the predisposing, precipitating, and
      perpetuating factors related to eating disorders. The client-therapist
      relationship is central to this model as demonstrated by a case illustration.

PMID- 11590617
TI  - High-impact therapy for smoking cessation.
AB  - Cigarette smoking is the leading cause of preventable death and disability-and
      thus an issue of considerable importance to psychotherapists. The majority of
      smoking-cessation programs available to the public uses an effective group
      format, but it remains underused. Many smokers who seek treatment request
      individual counseling; however, empirically based individual treatments are still
      in the early stages of development. High-impact therapy is a form of short-term
      dynamic psychotherapy adapted by the authors for the treatment of the hard-core
      smoker. It recognizes that the relationship among smoking, life stressors,
      personality factors, and psychological disorders is complex, and it intervenes
      using motivational and defense-challenging techniques. One of the main and
      distinctive features of this model is the emphasis on emotional arousal to
      facilitate the mastery of emotional conflict, making this a high-impact form of
      psychotherapy.

PMID- 11590618
TI  - Depression in chronic medical illness: the case of coronary heart disease.
AB  - Depression is an important predictor of morbidity and mortality in patients with
      coronary disease, particularly after myocardial infarction, independent of
      previous cardiac history or CAD severity. Depression also is associated with poor
      long-term psychosocial outcomes. The prevalence of major depression among post-MI
      patients is 15 to 20%, with an additional 27% reporting symptoms of minor
      depression. This article briefly reviews the literature on depression in patients
      with coronary disease, including previously published efforts to treat the
      disorder in this group. A case review then is provided, highlighting important
      aspects of treatment.

PMID- 11590619
TI  - Improved procedure for fluorescence in situ hybridization on tissue microarrays.
AB  - BACKGROUND: The recently developed tissue microarray (TMA) technology allows the
      arrangement of up to a thousand tissue specimens on a single microscope slide.
      This technology enables researchers to perform gene copy number studies on very
      large series of archival formalin-fixed tissues using fluorescence in situ
      hybridization (FISH). However, the hybridization properties of individual
      archival specimens can vary considerably. Therefore a highly optimized protocol
      is needed to fulfill the task of producing evaluable hybridization signals
      simultaneously in hundreds of specimens in a TMA. METHODS: The performance of two
      different FISH protocols, the standard protocol for paraffin embedded tissues and
      our new optimized protocol, was tested on TMAs using probes for the HER-2 and
      ZNF217 genes as well as the chromosome 17 centromere. RESULTS: The new protocol
      resulted in greatly increased signal intensity and an almost 30% increase in the
      number of tissue samples with evaluable hybridization signals. CONCLUSIONS: Our
      improved protocol for FISH on TMAs provides standardized hybridization conditions
      leading to high-quality hybridization signals in the majority of specimens. The
      increases in the signal intensity and the number of evaluable samples are
      extremely important for the successful analyses of TMAs by FISH and will allow
      the utilization of the TMA technology in its full potential.

PMID- 11590620
TI  - Enrichment during transdominant genetic experiments using a flow sorter.
AB  - BACKGROUND: Flow cytometry, in combination with retroviral expression libraries,
      is a powerful tool for genetic experimentation in mammalian cells. Expression
      libraries are transduced into cells engineered with a fluorescent reporter.
      Sorting for either bright or dim cells allows enrichment for specific inhibitors
      that alter reporter activity. This strategy has been used to isolate peptides and
      RNAs that either activate or suppress defined biochemical pathways. METHODS:
      Several variables contribute to the enrichment process: (1) the background of the
      fluorescence bioassay; (2) the mean fluorescence ratio between the induced and
      noninduced reporter cell populations; (3) the genetic penetrance, or strength, of
      the inhibitor; and (4) the multiplicity of infection (MOI). An experimental and
      theoretical analysis, including computer modeling, of these issues in the context
      of a mammalian cell bioassay was undertaken. RESULTS: MOI measurements were shown
      to be problematic. High MOI had little effect on enrichment early in the cycling
      process but a significant effect at later stages. Penetrance and background were
      critical throughout the process. Enrichments within about twofold of the
      theoretical maximum were observed. CONCLUSIONS: Caution should be exercised in
      MOI determination because of the danger of significant underestimation. High MOI
      is potentially advantageous early in the selection process but hinders enrichment
      in the later rounds. Modeling shows that MOI, assay background and clone
      penetrance are the principal variables that determine the success of
      transdominant selections by FACS.

PMID- 11590621
TI  - A new flow cytometric method to follow DNA gap filling during nucleotide excision
      repair of UVc-induced damage.
AB  - BACKGROUND: Several methods have been developed for studying the kinetics of DNA
      repair after exposure of cells to ultraviolet (UV) light, such as conventional
      assays measuring unscheduled DNA synthesis (UDS). In this study, we have
      developed an accurate and rapid method to follow DNA gap filling during
      nucleotide excision repair (NER) in normal human fibroblasts (NHFs) in response
      to UV-induced damage. METHODS: After UVc irradiation, aphidicolin was added to
      the culture to hold repair patches open. This allowed an efficient incorporation
      of biotin-21-dUTP during an endogenous DNA repair synthesis that was detected by
      flow cytometry. RESULTS: We showed that the DNA gap filling after UVc irradiation
      in NHFs increased with time up to 10 h after irradiation and that no repair
      synthesis activity could be detected in XP-A fibroblasts. Furthermore, this
      activity was UVc dose dependent up to 20 J/m2. These results correlated well with
      those of the UDS assay. Interestingly, addition of aphidicolin at different time
      points after UVc irradiation, thus allowing endogenous repair synthesis in the
      absence of biotin-21-dUTP, demonstrated that the response of the NER system
      occurred extremely rapidly after irradiation. CONCLUSIONS: This method may be a
      reliable and simple alternative to other techniques measuring UDS. Practical
      advantages include the rapidity of the method, no need for radioactivity, and the
      possibility to use a second and/even a third flow marker to analyse cell cycle
      and heterogeneous cell populations concomitantly.

PMID- 11590622
TI  - Validation of flow cytometric competitive binding protocols and characterization
      of fluorescently labeled ligands.
AB  - BACKGROUND: Fluorescently labeled ligands and flow cytometric methods allow
      quantification of receptor-ligand binding. Such methods require calibration of
      the fluorescence of bound ligands. Moreover, binding of unlabeled ligands can be
      calculated based on their abilities to compete with a labeled ligand. In this
      study, calibration parameters were determined for six fluorescently labeled N
      formyl peptides that bind to receptors on neutrophils. Two of these ligands were
      then used to develop and validate competitive binding protocols for determining
      binding constants of unlabeled ligands. METHODS: Spectrofluorometric and flow
      cytometric methods for converting relative flow cytometric intensities to number
      of bound ligand/cell were extended to include peptides labeled with fluorescein,
      Bodipy, and tetramethylrhodamine. The validity of flow cytometric competitive
      binding protocols was tested using two ligands with different fluorescent
      properties that allowed determination of rate constants both directly and
      competitively for one ligand, CHO-NLFNYK-tetramethylrhodamine. RESULTS:
      Calibration parameters were determined for six fluorescently-labeled N-formyl
      peptides. Equilibrium dissociation constants for these ligands varied over two
      orders of magnitude and depended upon the peptide sequence and the molecular
      structure of the fluorescent tag. Kinetic rate constants for CHO-NLFNYK
      tetramethylrhodamine determined directly or in competition with CHO-NLFNYK
      fluorescein were statistically identical. CONCLUSIONS: Combination of
      spectrofluorometric and flow cytometric methods allows convenient calculation of
      calibration parameters for a series of fluorescent ligands that bind to the same
      receptor site. Competitive binding protocols have been independently validated.

PMID- 11590623
TI  - A novel flow cytometric assay to quantify soluble CD14 concentration in human
      serum.
AB  - BACKGROUND: CD14, the major lipopolysaccharide (LPS)-binding protein of myeloid
      cells, is found as a soluble molecule in human serum. Recent data describe the
      presence of elevated soluble CD14 (sCD14) concentration in various disorders,
      confirming disease activity. A novel, easy, and rapid flow cytometric assay was
      developed to measure sCD14 levels in serum. METHODS: The assay is based on the
      competition between membrane-expressed CD14 of isolated monocytes from healthy
      volunteers and sCD14 in the sample sera for binding to anti-CD14 monoclonal
      antibodies (mAb; 26ic or 60bca). The amount of cell-associated mAb is determined
      with a fluorescein isothiocyanate (FITC)-labeled anti-mouse conjugate and flow
      cytometry. The fluorescence signal is inversely proportional with the amount of
      serum sCD14. Using dilutions of a standard serum, the concentration of sCD14 in
      the samples is calculated and compared with results obtained by a commercial
      sCD14 enzyme-linked immunosorbent assay (ELISA). RESULTS: After optimization, the
      assay showed log-log linearity of 122.1-984.7 ng/ml sCD14 using mAb 26ic and 29.5
      246.2 ng/ml sCD14 using mAb 60bca. It revealed similar results as the ELISA (mAb
      26ic: r = 0.88, mAb 60bca: r = 0.92) and provided significantly elevated sCD14
      levels in systemic lupus erythematosus patients compared with controls (26ic:
      2,213 versus 1,676 ng/ml, P < 0.002; 60bca: 2,625 versus 1,907 ng/ml, P <
      0.0002). Receiver operating characteristic curve analysis suggested a reasonable
      diagnostic efficacy of sCD14 quantification in this autoimmune disease.
      CONCLUSIONS: The method is easy, rapid, sensitive, and can be used in the follow
      up of patients suffering from sepsis or chronic inflammatory disorders.

PMID- 11590625
TI  - Relative frequency of malaria pigment-carrying monocytes of nonimmune and semi
      immune patients from flow cytometric depolarized side scatter.
AB  - BACKGROUND: Recently, it was observed that malaria can be detected by performing
      automated complete blood count analysis including depolarization measurement of
      scattered laser light. To explain large discrepancies in sensitivity and
      specificity observed in semi-immune and nonimmune malaria patients, we determined
      the relative frequencies of malaria pigment-carrying monocytes (PCM) by flow
      cytometric measurements combined with rare event analysis. METHODS: An
      experimental cell-sorting unit utilizing argon, krypton, and helium-neon lasers
      measured the relative frequencies of leukocytes of malaria patients. Single white
      blood cells showing high intensity in their depolarized side scatter were sorted
      for subsequent microscopic analysis. RESULTS: From microscopic inspection of
      sorted cells, we identified malaria PCM as a distinct cluster in scatter diagrams
      that is well separated from normal leukocytes. For nonimmune patients, the
      average relative frequency of PCM is 1.5 x 10(-4) (median), for semi-immune
      patients 8.8 x 10(-4), and for malaria-negative persons 4.4 x 10(-6). Results
      derived from depolarized side scatter at 488, 633, or 647 nm agree well.
      Furthermore, malaria pigment-carrying neutrophilic granulocytes were identified
      microscopically after sorting. We discuss briefly how pigment-carrying
      neutrophils might be differentiated from normal leukocytes and PCM by using flow
      cytometry and measuring depolarized side scatter at two wavelengths. CONCLUSION:
      Our results confirm the feasibility of malaria detection by flow cytometry for
      semi-immune patients and extend malaria detection to nonimmune patients with low
      frequencies of PCM. High sensitivity and specificity for malaria detection were
      obtained.

PMID- 11590624
TI  - Circulating CD33+ large mononuclear cells contain three distinct populations with
      phenotype of putative antigen-presenting cells including myeloid dendritic cells
      and CD14+ monocytes with their CD16+ subset.
AB  - BACKGROUND: In peripheral blood, myeloid markers identify a heterogeneous mixture
      of cells in transit from the bone marrow to peripheral tissues. Similarly, HLA
      class II DR expression usually identifies mononuclear cells with the potential
      for developing antigen-presenting activity. We gathered putative antigen
      presenting cells bearing myeloid markers (My-APC) to study their composition by
      cell surface phenotype. METHODS: To gather and dissect My-APC phenotype while
      excluding lymphocytes and granulocytes, we developed a strategy based on staining
      red cell-lysed peripheral blood and gating cells bearing myeloid markers and
      physical parameters of large mononuclear cells. RESULTS: Phenotypic analysis
      within the My-APC gate showed three distinct populations. The largest fraction
      was constituted by CD14+ monocytes that extended into the other two populations,
      each expressing gradually lower levels of CD14 surface antigen along with
      increasing levels of CD16 and CD2, respectively. The CD16 and CD2 expression
      patterns extended from CD16+CD14+ or CD2+CD14+ double- positive intermediate
      cells toward each single positive subset, but they were reciprocally exclusive.
      Interestingly, CD2+CD14- cells within the My-APC gate were equivalent to myeloid
      dendritic cell precursors (pre-DC) defined previously by the absence of lineage
      markers and expression of HLA-DR and myeloid markers. Phenotypic analysis of each
      population revealed differences in the expression of costimulatory molecules and
      CD62L. CONCLUSIONS: This novel analytical approach allowed us to distinguish
      circulating My-APC in three subsets and to identify relationships between
      monocytes and other related myeloid populations including DC.

PMID- 11590626
TI  - Probability binning and testing agreement between multivariate immunofluorescence
      histograms: extending the chi-squared test.
AB  - BACKGROUND: A key problem in immunohistochemistry is assessing when two sample
      histograms are significantly different. One test that is commonly used for this
      purpose in the univariate case is the chi-squared test. Comparing multivariate
      distributions is qualitatively harder, as the "curse of dimensionality" means
      that the number of bins can grow exponentially. For the chi-squared test to be
      useful, data-dependent binning methods must be employed. An example of how this
      can be done is provided by the "probability binning" method of Roederer et al.
      (1,2,3). METHODS: We derive the theoretical distribution of the probability
      binning statistic, giving it a more rigorous foundation. We show that the null
      distribution is a scaled chi-square, and show how it can be related to the
      standard chi-squared statistic. RESULTS: A small simulation shows how the
      theoretical results can be used to (a) modify the probability binning statistic
      to make it more sensitive and (b) suggest variant statistics which, while still
      exploiting the data-dependent strengths of the probability binning procedure, may
      be easier to work with. CONCLUSIONS: The probability binning procedure
      effectively uses adaptive binning to locate structure in high-dimensional data.
      The derivation of a theoretical basis provides a more detailed interpretation of
      its behavior and renders the probability binning method more flexible.

PMID- 11590627
TI  - A flow cytometry assay simultaneously detects independent apoptotic parameters.
AB  - BACKGROUND: Apoptosis regulation is of fundamental importance in tissue
      homeostasis and in the pathogenesis of a variety of diseases. Different
      cytofluorometric methods are used to investigate apoptotic events. We set up a
      method to simultaneously evaluate mitochondria depolarization, cell morphology
      changes, and loss of plasma membrane asymmetry and integrity, thus increasing the
      information and minimizing errors in the analysis of the apoptotic process.
      METHODS: Jurkat T cells were induced to undergo apoptosis with different agents.
      They were labeled with (1) the mitochondrion-selective probes
      tetramethylrhodamine methyl ester (TMRM) or chloromethyl X-rosamine (CMXRos),
      which do not accumulate in depolarized mitochondria; (2) Annexin V-fluorescein
      isothyocianate (FITC) to detect phosphatidylserine (PS) exposure on the cell
      surface; and (3) propidium iodide (PI) to assess loss of plasma membrane
      integrity. Cell morphology changes were studied following variations in light
      scatter parameters. RESULTS: This is a fast, reliable, and reproducible technique
      to detect simultaneously independent apoptotic changes by cytofluorometric
      inspection. TMRM is more effective than CMXRos in responding to variations in the
      electrochemical gradient of mitochondria. CONCLUSIONS: This technique allows us
      to integrate the analysis and to follow the kinetics of different apoptotic cell
      changes.

PMID- 11590628
TI  - Randomized clinical trials with added rescue medication: some approaches to their
      analysis and interpretation.
AB  - Patients in some randomized clinical trials may start additional non-randomized
      medication because of an exacerbation of symptoms or insufficient therapeutic
      effect. Typically this rescue medication reduces the observed treatment effect in
      intention-to-treat analysis. We discuss methods of analysis which take account of
      rescue medication in order to achieve a more meaningful comparison of the
      randomized treatments, focusing on trials with a repeated quantitative outcome.
      Ignoring all data after rescue is likely to be biased because rescued patients
      are a highly selected group. Instead we propose using methods based on ranks or
      multilevel models. The rank-based methods assume that rescued patients have
      especially bad underlying outcomes. The multilevel regression model relates a
      patient's outcome to allocated treatment and rescue status at each time, and
      requires correct modelling of all prognostic factors which predict starting
      rescue medication and of the covariance between outcomes measured at different
      times. We also describe sensitivity analyses over a range of possible models for
      the effect of rescue medication. We illustrate these methods in a trial in
      Parkinson's disease. It appears that adjustment for rescue medication will not
      radically alter the randomized treatment comparison unless rescue medication is
      substantially imbalanced between randomized groups and has a substantial effect
      on the outcome.

PMID- 11590629
TI  - A three-stage clinical trial design for rare disorders.
AB  - Many clinical trials of uncommon diseases are underpowered because of the
      difficulty of recruiting adequate numbers of subjects. We propose a clinical
      trial design with improved statistical power compared to the traditional
      randomized trial for use in clinical trials of rare diseases. The three-stage
      clinical trial design consists of an initial randomized placebo-controlled stage,
      a randomized withdrawal stage for subjects who responded, and a third randomized
      stage for placebo non-responders who subsequently respond to treatment. Test
      level and power were assessed by computer-intensive exact calculations. The three
      stage clinical trial design was found to be consistently superior to the
      traditional randomized trial design in all cases examined, with sample sizes
      typically reduced by 20 per cent to 30 per cent while maintaining comparable
      power. When a treatment clearly superior to placebo was considered, our design
      reached a power of 75 per cent with a sample of 21 patients compared with the 52
      needed to attain this power when only a randomized controlled trial was used. In
      situations where patient numbers are limited, a three-stage clinical trial design
      may be a more powerful design than the traditional randomized trial for detecting
      clinical benefits.

PMID- 11590630
TI  - Evaluation of surrogate endpoints in randomized experiments with mixed discrete
      and continuous outcomes.
AB  - A statistical definition of surrogate endpoints as well as validation criteria
      was first presented by Prentice. Freedman et al. supplemented these criteria with
      the so-called proportion explained. Buyse and Molenberghs pointed to inadequacies
      of these criteria and suggested a new definition of surrogacy based on (i) the
      relative effect linking the overall effect of treatment on both endpoints and
      (ii) an individual-level measure of agreement between both endpoints. Using data
      from a randomized trial, they showed how a potential surrogate endpoint can be
      studied using a joint model for the surrogate and the true endpoint. Whereas
      Buyse and Molenberghs restricted themselves to the fairly simple cases of jointly
      normal and jointly binary outcomes, we treat the situation where the surrogate is
      binary and the true endpoint is continuous, or vice versa. In addition, we
      consider the case of ordinal endpoints. Further, Buyse et al. extended the
      approach of Buyse and Molenberghs to a meta-analytic context. We will adopt a
      similar approach for responses of a mixed data type.

PMID- 11590631
TI  - Within-subject exposure dependency in case-crossover studies.
AB  - In the case-crossover design, only cases are sampled and the hazard ratio is
      estimated from within-subject comparisons of exposures at the event time and in M
      control periods prior to the event. We consider the effect of within-subject
      dependence of exposures in successive time periods. We show that estimates
      obtained from the conditional logistic model are biased. This bias disappears if
      the distribution of exposures in the M+1 successive time intervals is
      exchangeable. In contrast, the Mantel-Haenszel estimator for the odds ratio is
      approximately unbiased provided that exposures are stationary. Suitable methods
      of analysis of case-crossover designs using maximum likelihood may be derived
      from cohort rather than case-control models.

PMID- 11590632
TI  - Dynamic linear model and SARIMA: a comparison of their forecasting performance in
      epidemiology.
AB  - One goal of a public health surveillance system is to provide a reliable forecast
      of epidemiological time series. This paper describes a study that used data
      collected through a national public health surveillance system in the United
      States to evaluate and compare the performances of a seasonal autoregressive
      integrated moving average (SARIMA) and a dynamic linear model (DLM) for
      estimating case occurrence of two notifiable diseases. The comparison uses
      reported cases of malaria and hepatitis A from January 1980 to June 1995 for the
      United States. The residuals for both predictor models show that they were
      adequate tools for use in epidemiological surveillance. Qualitative aspects were
      considered for both models to improve the comparison of their usefulness in
      public health. Our comparison found that the two forecasting modelling techniques
      (SARIMA and DLM) are comparable when long historical data are available (at least
      52 reporting periods). However, the DLM approach has some advantages, such as
      being more easily applied to different types of time series and not requiring a
      new cycle of identification and modelling when new data become available.

PMID- 11590633
TI  - Allocation of subjects to test null relative risks smaller than one.
AB  - Allocating a proportion k'=1/(1+ radicalr(0)) of subjects to an intervention is a
      practical approach to approximately maximize power for testing whether an
      intervention reduces relative risk of disease below a null ratio r(0)<1.
      Furthermore, allocating k'(s), a convenient fraction close to k', to intervention
      performs nearly as well; for example, allocating k'(s)=3/5 for 0.5> or
      =r(0)>0.33,2/3 for 0.33> or =r(0)>0.17 and 3/4 for 0.17> or =r(0)> or =0.10. Both
      k' and k'(s) are easily calculated and invariant to alterations in disease rate
      estimates under null and alternative hypotheses, when r(0) remains constant. In
      examples that we studied, allocating k' (or k'(s)) subjects to intervention
      achieved close to the minimum possible sample size, given test size and power
      (equivalently, maximum power, given test size and sample size), for likelihood
      score tests. Compared to equal allocation, k' and k'(s) reduced sample sizes by
      amounts ranging from approximately 5.5 per cent for r(0)=0.50 to approximately 24
      per cent for r(0)=0.10. These sample size savings may be particularly important
      for large studies of prophylactic interventions such as vaccines. While k' was
      derived from variance minimization for an arcsine transformation, we do not
      recommend the arcsine test, since its true size exceeded the nominal value. In
      contrast, the true size for the uncorrected score test was less than the nominal
      size. A skewness correction made the size of the score test very close to the
      nominal level and slightly increased power. We recommend using the score test, or
      the skewness-corrected score test, for planing studies designed to show a ratio
      of proportions is less than a prespecified null ratio r(0)<1.

PMID- 11590634
TI  - Accuracy of point predictions in survival analysis.
AB  - Survival time prediction is important in many applications, particularly for
      patients diagnosed with terminal diseases. A measure of prediction error taken
      from the medical literature is advocated as a practicable method of quantifying
      reliability of point predictions. Optimum predictions are derived for familiar
      survival models and the accuracy of these predictions is investigated. We argue
      that poor predictive capability is inherent to standard survival models with
      realistic parameter values. A lung cancer example is used to illustrate
      difficulties in prediction in practice.

PMID- 11590635
TI  - Modelling variation of lower leg length growth in early life.
AB  - We consider the estimation of sources of variation for panel data with repeated
      measurements. With no repeated measurements and known measurement error, models
      for variation decomposition have been proposed when there are one or more types
      of measurements. Estimation was performed using the EM algorithm accompanied by
      model augmentation that demands more computational efforts. In this article we
      extend previous variation models and modify the estimation methods in order to
      estimate various variation components after eliminating the unknown effects of
      measurement error. Specifically, methods that dispense with model augmentation
      and estimation of time-dependent covariates are considered. A set of lower leg
      length data from Chinese infants is analysed by using the proposed model.
      Interestingly, our results are consistent with the well-accepted three-phase
      (infancy-childhood-puberty) growth transition proposition for human growth.
      Moreover, gender effect is found to be time-varying.

PMID- 11590636
TI  - Bayesian analysis of logistic regression with an unknown change point and
      covariate measurement error.
AB  - We discuss Bayesian estimation of a logistic regression model with an unknown
      threshold limiting value (TLV). In these models it is assumed that there is no
      effect of a covariate on the response under a certain unknown TLV. The estimation
      of these models in a Bayesian context by Markov chain Monte Carlo (MCMC) methods
      is considered with focus on the TLV. We extend the model by accounting for
      measurement error in the covariate. The Bayesian solution is compared with the
      likelihood solution proposed by Kuchenhoff and Carroll using a data set
      concerning the relationship between dust concentration in the working place and
      the occurrence of chronic bronchitis.

PMID- 11590637
TI  - The applications of capture-recapture models to epidemiological data.
AB  - Capture-recapture methodology, originally developed for estimating demographic
      parameters of animal populations, has been applied to human populations. This
      tutorial reviews various closed capture-recapture models which are applicable to
      ascertainment data for estimating the size of a target population based on
      several incomplete lists of individuals. Most epidemiological approaches merging
      different lists and eliminating duplicate cases are likely to be biased
      downwards. That is, the final merged list misses those who are in the population
      but were not ascertained in any of the lists. If there are no matching errors,
      then the duplicate information collected from a capture-recapture experiment can
      be used to estimate the number of missed under proper assumptions. Three
      approaches and their associated estimation procedures are introduced: ecological
      models; log-linear models, and the sample coverage approach. Each approach has
      its unique way of incorporating two types of source dependencies: local (list)
      dependence and dependence due to heterogeneity. An interactive program, CARE (for
      capture-recapture) developed by the authors is demonstrated using four real data
      sets. One set of data deals with infection by the acute hepatitis A virus in an
      outbreak in Taiwan; the other three sets are ascertainment data on diabetes,
      spina bifida and infants' congenital anomaly discussed in the literature. These
      data sets provide examples to show the usefulness of the capture-recapture method
      in correcting for under-ascertainment. The limitations of the methodology and
      some cautionary remarks are also discussed.

PMID- 11590638
TI  - Physiological noise in oxygenation-sensitive magnetic resonance imaging.
AB  - The physiological noise in the resting brain, which arises from fluctuations in
      metabolic-linked brain physiology and subtle brain pulsations, was investigated
      in six healthy volunteers using oxygenation-sensitive dual-echo spiral MRI at 3.0
      T. In contrast to the system and thermal noise, the physiological noise
      demonstrates a signal strength dependency and, unique to the metabolic-linked
      noise, an echo-time dependency. Variations of the MR signal strength by changing
      the flip angle and echo time allowed separation of the different noise components
      and revealed that the physiological noise at 3.0 T (1) exceeds other noise
      sources and (2) is significantly greater in cortical gray matter than in white
      matter regions. The SNR in oxygenation-sensitive MRI is predicted to saturate at
      higher fields, suggesting that noise measurements of the resting brain at 3.0 T
      and higher may provide a sensitive probe of functional information.

PMID- 11590639
TI  - Advances in sensitivity encoding with arbitrary k-space trajectories.
AB  - New, efficient reconstruction procedures are proposed for sensitivity encoding
      (SENSE) with arbitrary k-space trajectories. The presented methods combine
      gridding principles with so-called conjugate-gradient iteration. In this fashion,
      the bulk of the work of reconstruction can be performed by fast Fourier transform
      (FFT), reducing the complexity of data processing to the same order of magnitude
      as in conventional gridding reconstruction. Using the proposed method, SENSE
      becomes practical with nonstandard k-space trajectories, enabling considerable
      scan time reduction with respect to mere gradient encoding. This is illustrated
      by imaging simulations with spiral, radial, and random k-space patterns.
      Simulations were also used for investigating the convergence behavior of the
      proposed algorithm and its dependence on the factor by which gradient encoding is
      reduced. The in vivo feasibility of non-Cartesian SENSE imaging with iterative
      reconstruction is demonstrated by examples of brain and cardiac imaging using
      spiral trajectories. In brain imaging with six receiver coils, the number of
      spiral interleaves was reduced by factors ranging from 2 to 6. In cardiac real
      time imaging with four coils, spiral SENSE permitted reducing the scan time per
      image from 112 ms to 56 ms, thus doubling the frame-rate.

PMID- 11590640
TI  - Unifying linear prior-information-driven methods for accelerated image
      acquisition.
AB  - In the ongoing quest for faster imaging and higher spatial resolution, several
      methods have been developed to speed up data acquisition by incorporating prior
      information about the object being imaged. This study shows that many of these
      methods can be integrated into a single common equation. The unified framework
      provides a conceptual link that facilitates comparison among these methods to
      reveal their strengths and weaknesses. By considering the limitations of existing
      methods, a new member in this class of methods was developed. The broad-use
      linear acquisition speed-up technique (BLAST) uses the estimated amount of change
      within the FOV as prior information. BLAST has the flexibility of incorporating a
      variable amount of prior information to avoid the misleading appearance of
      "phantom features," which arise from overconstraining the reconstruction.
      Examples from dynamic imaging and MR thermometry are shown.

PMID- 11590641
TI  - 4D deformation modeling of cortical disease progression in Alzheimer's dementia.
AB  - This work describes the development of a model of cerebral atrophic changes
      associated with the progression of Alzheimer's disease (AD). Linear registration,
      region-of-interest analysis, and voxel-based morphometry methods have all been
      employed to elucidate the changes observed at discrete intervals during a disease
      process. In addition to describing the nature of the changes, modeling disease
      related changes via deformations can also provide information on temporal
      characteristics. In order to continuously model changes associated with AD,
      deformation maps from 21 patients were averaged across a novel z-score disease
      progression dimension based on Mini Mental State Examination (MMSE) scores. The
      resulting deformation maps are presented via three metrics: local volume loss
      (atrophy), volume (CSF) increase, and translation (interpreted as representing
      collapse of cortical structures). Inspection of the maps revealed significant
      perturbations in the deformation fields corresponding to the entorhinal cortex
      (EC) and hippocampus, orbitofrontal and parietal cortex, and regions surrounding
      the sulci and ventricular spaces, with earlier changes predominantly lateralized
      to the left hemisphere. These changes are consistent with results from post
      mortem studies of AD.

PMID- 11590642
TI  - Dynamic spiral MRI of pulmonary gas flow using hyperpolarized (3)He: preliminary
      studies in healthy and diseased lungs.
AB  - An optimized interleaved-spiral pulse sequence, providing high spatial and
      temporal resolution, was developed for dynamic imaging of pulmonary ventilation
      with hyperpolarized (3)He, and tested in healthy volunteers and patients with
      lung disease. Off-resonance artifacts were minimized by using a short data
      sampling period per interleaf, and gradient-fidelity errors were compensated for
      by using measured k-space trajectories for image reconstruction. A nonsequential
      acquisition order was implemented to improve image quality during periods of
      rapid signal change, such as early inspiration. Using a sliding-window
      reconstruction, cine-movies with a frame rate of 100 images per second were
      generated. Dynamic images demonstrating minimal susceptibility- and motion
      induced artifacts were obtained in sagittal, coronal, and axial orientations. The
      pulse sequence had the flexibility to image multiple slices almost
      simultaneously. Our initial experience in healthy volunteers and subjects with
      lung pathology demonstrated the potential of this new tool for capturing the
      features of lung gas-flow dynamics.

PMID- 11590643
TI  - Significant precision improvement for temperature mapping.
AB  - MR temperature measurements are important for applications such as the evaluation
      of thermal therapies and radiofrequency (RF) coil heating effects. In this work
      the spherical mean value (SMV) method has been applied to significantly improve
      the precision of MR temperature mapping in a homogeneous gel phantom. Temperature
      increase maps of the phantom were obtained with three-dimensional (3D) MR phase
      difference mapping after heating with the RF coil. The temperature-increase
      distribution in most regions in the phantom is a harmonic function with the mean
      value property. Based on this property, the precision of temperature-increase
      maps was improved up to sixfold with the SMV method. Comparison of this method
      with conventional smoothing, further precision improvement, and the in vivo
      application of the SMV method are discussed.

PMID- 11590644
TI  - Characterization of trabecular bone by dipolar demagnetizing field MRI.
AB  - A multiple spin-echo (MSE) sequence has been applied for the first time to study
      trabecular bone ex vivo. The second echo generated by the demagnetizing field
      presents discrete drops in signal intensity for certain values of the pitch of
      the magnetization helix created by the correlation gradient. These dips may
      reflect characteristic pore sizes in the trabecular bone specimens. This
      hypothesis is supported by similar experiments performed on a phantom with
      uniform pore size distribution. Trabecular bone images weighted in the MSE
      contrast mechanism are reported.

PMID- 11590645
TI  - Embedded MR fluoroscopy: high temporal resolution real-time imaging during high
      spatial resolution 3D MRA acquisition.
AB  - A method termed "embedded fluoroscopy" for simultaneously acquiring a real-time
      sequence of 2D images during acquisition of a 3D image is presented. The 2D
      images are formed by periodically sampling the central phase encodes of the slab
      select direction during the 3D acquisition. The tradeoffs in spatial and temporal
      resolution are quantified by two parameters: the "redundancy" (R), the fraction
      of the 3D acquisition sampled more than once; and the "effective temporal
      resolution" (T), the time between temporal updates of the central views. The
      method is applied to contrast-enhanced MR angiography (CE-MRA). The contrast
      bolus dynamics are portrayed in real time in the 2D image sequence while a high
      resolution 3D image is being acquired. The capability of the 2D acquisition to
      measure contrast enhancement with only a 5% degradation of the spatial resolution
      of the 3D CE-MR angiogram is shown theoretically. The method is tested clinically
      in 15 CE-MRA patient studies of the carotid and renal arteries.

PMID- 11590646
TI  - Quantitative proton MR spectroscopic imaging of normal human cerebellum and brain
      stem.
AB  - Quantitative, multislice proton MR spectroscopic imaging (MRSI) was used to
      investigate regional metabolite levels and ratios in the normal adult human
      posterior fossa. Six normal volunteers (36 +/- 3 years, five male, one female)
      were scanned on a 1.5 T scanner using multislice MRSI at long echo time (TE 280
      msec). The entire cerebellum was covered using three oblique-axial slice
      locations, which also included the pons, mid-brain, insular cortex, and parieto
      occipital lobe. Concentrations of N-acetylaspartate (NAA), choline (Cho), and
      creatine (Cr) were estimated using the phantom replacement technique. Regional
      variations of the concentrations were assessed using ANOVA (P < 0.05). High
      resolution MRSI data was obtained in all subjects and brain regions examined.
      Metabolite concentrations (mM) (mean +/- SD) were as follows: cerebellar vermis:
      2.3 +/- 0.4, 8.8 +/- 1.7 and 7.6 +/- 1.0 for Cho, Cr, and NAA respectively;
      cerebellar hemisphere: 2.2 +/- 0.6, 8.9 +/- 2.1, 7.5 +/- 0.8; pons 2.2 +/- 0.5,
      4.3 +/- 1.1, 8.3 +/- 0.9; insular cortex, 1.8 +/- 0.5, 7.8 +/- 2, 8.0 +/- 1.1,
      parieto-occipital gray matter, 1.3 +/- 0.3, 5.7 +/- 1.1, 7.2 +/- 0.9, and
      occipital white matter, 1.4 +/- 0.3, 5.3 +/- 1.3, 7.5 +/- 0.8. Consistent with
      previous reports, significantly higher levels of Cr were found in the cerebellum
      compared to parieto-occipital gray and occipital white matter, and pons (P <
      0.0001). NAA was essentially uniformly distributed within the regions chosen for
      analysis, with the highest level in the pons (P < 0.04). Cho was significantly
      higher in the cerebellum and pons than parieto-occipital gray and occipital white
      matter (P < 0.002) and was also higher in the pons than in the insular cortex (P
      < 0.05). Quantitative multislice MRSI of the posterior fossa is feasible and
      significant regional differences in metabolite concentrations were found.

PMID- 11590647
TI  - Comparison of methods for reduction of lipid contamination for in vivo proton MR
      spectroscopic imaging of the brain.
AB  - In vivo proton MR spectroscopic imaging (MRSI) of human brain is complicated by
      the presence of a strong signal from subcutaneous lipids, which may result in
      signal contamination in metabolite images obtained following Fourier-transform
      reconstruction. In this study, two approaches for reduction of lipid
      contamination--using postprocessing and additional data acquisition--are
      compared. The first uses extrapolation of k-space information for subcutaneous
      lipid, which has been applied to data obtained using conventional fully phase
      encoded MRSI with circularly sampled k-space or echo-planar spectroscopic imaging
      (EPSI). The second uses a dual EPSI technique that combines multiple-averaged
      central k-space data with a single EPSI acquisition of additional information
      that is used for improved lipid reconstruction. Comparisons are carried out with
      data obtained from human brain in vivo at 1.5 T with short and medium TEs.
      Results demonstrate that the performance of both methods for reducing the effects
      of lipid contamination is similar, and that both are limited by the effects of
      instrumental instabilities and subject motion, which also depend on the
      acquisition method used.

PMID- 11590648
TI  - Sensitivity-encoded spectroscopic imaging.
AB  - Sensitivity encoding (SENSE) offers a new, highly effective approach to reducing
      the acquisition time in spectroscopic imaging (SI). In contrast to conventional
      fast SI techniques, which accelerate k-space sampling, this method permits
      reducing the number of phase encoding steps in each phase encoding dimension of
      conventional SI. Using a coil array for data acquisition, the missing encoding
      information is recovered exploiting knowledge of the distinct spatial
      sensitivities of the individual coil elements. In this work, SENSE is applied to
      2D spectroscopic imaging. Fourfold reduction of scan time is achieved at
      preserved spectral and spatial resolution, maintaining a reasonable SNR. The
      basic properties of the proposed method are demonstrated by phantom experiments.
      The in vivo feasibility of SENSE-SI is verified by metabolic imaging of N
      acetylaspartate, creatine, and choline in the human brain. These results are
      compared to conventional SI, with special attention to the spatial response and
      the SNR.

PMID- 11590649
TI  - Extravascular contribution of blood oxygenation level-dependent signal changes: a
      numerical analysis based on a vascular network model.
AB  - In this study, the extravascular (EV) contribution to blood oxygenation level
      dependent (BOLD) signal changes was evaluated, based on a numerical analysis of
      the nondimensional Bloch-Torrey equation for a vascular network model of randomly
      oriented paramagnetic vessels. From a statistical point of view, the
      susceptibility-induced EV BOLD signal changes for both gradient- and spin-echoes
      are shown to be proportional to cerebral blood volume (CBV). These changes can be
      expressed by a function of two nondimensional parameters: one represents the
      characteristic phase change of the signal induced by the deoxyhemoglobin
      containing vessels, and the other represents a diffusion effect relative to the
      vessel radius. The numerical results showed excellent agreement with the
      analytical solutions obtained previously for the regimes of small and large
      diffusion effects. Based on the numerical results for gradient- and spin-echoes,
      it is possible to show the dependence of the EV BOLD contribution on the echo
      time, the static magnetic field strength, and the stimulation-induced CBV change.
      This dependence can be demonstrated for vessels of small, intermediate, and large
      radii, which correspond respectively to the slow, intermediate, and fast
      diffusion regimes. A more realistic functional MRI (fMRI) simulation which
      includes an intravascular (IV) contribution is presented, with emphasis on the
      field strength dependence of the BOLD signal changes.

PMID- 11590650
TI  - MR-derived cerebral blood volume maps: issues regarding histological validation
      and assessment of tumor angiogenesis.
AB  - In an effort to develop MRI methods for the evaluation of tumor angiogenesis (new
      blood vessel formation), MRI-derived cerebral blood volume (CBV) information has
      been compared to histologic measures of microvessel density (MVD). Although MVD
      is a standard marker of angiogenesis, it is not a direct correlate of the volume
      measurements made with MRI, and therefore inappropriate for the development and
      validation of the MR techniques. Therefore, the goal of this study was to develop
      an approach by which MR measurements of CBV can be directly correlated. To this
      end, dynamic susceptibility contrast (DSC) MRI experiments were performed in six
      Fisher rats implanted with 9L gliosarcoma brain tumors. Subsequently, the
      circulation was perfused with a latex compound (Microfil), after which 50-microm
      tissue sections were analyzed for vessel count, diameter, and the fraction of
      area comprised of vessels. The results demonstrate that while fractional area
      (FA) does not provide a good measure of CBV, FA corrected for section thickness
      effects does. Whereas the FA in normal brain was found to be 13.03 +/- 1.83% the
      corrected FA, or fractional volume (FV), was 1.89 +/- 0.39%, a value in agreement
      with those reported in the literature for normal brain. Furthermore, while no
      significant difference was found between normal brain and tumor FA (P = 0.55),
      the difference was significant for FV (P = 0.036), as would be expected. And only
      with FV does a correlation with the MRI-derived CBV become apparent (r(S) =
      0.74). There was strong correlation (r(s) = 0.886) between the tumor / normal
      blood volume ratios as estimated by each technique, although the MR-ratio (1.56
      +/- 0.29) underestimated the histologic-ratio (2.35 +/- 0.75). Thus, the
      correlation of MRI CBV methods requires a measurement of fractional vessel area
      and correction of this area for section thickness effects. This new independent
      correlative measure should enable efficient and accurate progress in the
      development of MRI methods to evaluate tumor angiogenesis.

PMID- 11590651
TI  - Repetition time in echo planar functional MRI.
AB  - To date, surprisingly little attention has been directed toward determining the
      optimum TR in a functional imaging experiment. A survey of the literature reveals
      a wide range of TRs, but little justification for a specific TR. Long-TR
      functional imaging experiments provide maximum signal-to-noise ratio (SNR) in the
      raw images; allow for the collection of a large number of slice locations; and
      decrease the size of the data set acquired, simplifying storage and handling.
      This work, however, demonstrates that long-TR imaging sacrifices statistical
      power when the paradigm timing is held fixed. That is, for a fixed-run duration
      consisting of multiple activation/control blocks, shorter TR acquisitions (on the
      order of 1000 ms) provide better discrimination between the activated and
      nonactivated brain tissue regions than do long-TR acquisitions (on the order of
      4000 ms). Results are shown for modeling the functional imaging experiment and
      for three different paradigms performed on normal subjects.

PMID- 11590652
TI  - 3-D surface reconstruction of multiple sclerosis lesions using spherical
      harmonics.
AB  - A new approach to approximate the 3-D shape of multiple sclerosis (MS) lesions
      and to calculate their volumes is presented. The suggested method utilizes sets
      of MS lesion contours taken from segmented MR images and approximates their 3-D
      surfaces by spherical harmonics. This method was applied to obtain 3-D
      reconstructions of in vivo and simulated MS lesions and to calculate their
      volumes. The results show good geometrical approximations of the original MS
      lesions' 3-D shapes and good consistency in volume estimation independent of the
      size of the lesions. The average volume estimation error was smaller than the
      commonly used technique of slice stacking (15.5 +/- 13.4% and 13.1 +/- 10.1% vs.
      25.0 +/- 17.0%). The method presented here offers a tool for analyzing the
      geometrical characteristics of MS lesions in 3-D as well as their volumes. The
      geometrical information may potentially serve as an additional clinical index for
      monitoring the disease.

PMID- 11590653
TI  - Mapping the velocity vector onto the spin vector: two-dimensional velocity
      selective spin excitation for MR flow imaging.
AB  - This article presents a two-dimensional velocity-selective spin excitation (2D
      VSP) method that enables quantitative imaging of motion in two directions in a
      single scan, without the need for image subtraction or combination. It is based
      on the idea of mapping a 2D velocity vector directly onto the transverse
      magnetization vector, such that the signal intensity reflects the speed of
      motion, while the signal phase represents the direction of motion. Experimental
      demonstration is presented in conjunction with an analysis of the accuracy of
      this method. VSP methods are often limited by inconsistent static signal
      suppression under variable shim and RF conditions. By using adiabatic RF pulses
      in a 2D-VSP composite that possesses time-reversal symmetry, consistent
      background suppression of 30-fold or higher was demonstrated over experimental
      conditions of +/-200 Hz off-resonance and 30% RF field variation.

PMID- 11590654
TI  - Simultaneous antegrade/retrograde cardioplegia protects myocardium distal to a
      coronary occlusion: a study in isolated pig hearts.
AB  - This study was designed to assess the effects of simultaneous
      antegrade/retrograde cardioplegia (SARC) on myocardial perfusion and energy
      metabolism in the region supported by the occluded left anterior descending
      artery (LAD) in isolated pig hearts. It was found that injection of Gd-DTPA into
      the aorta during antegrade cardioplegia (AC) did not result in signal increase in
      the LAD region on T(1)-weighted images. During SARC, however, Gd-DTPA was
      detected in the LAD region with the contrast agent injected into the aorta and
      the coronary sinus (CS), respectively. This suggests that SARC delivered blood
      cardioplegia to the jeopardized myocardium through both arterial and venous
      perfusion routes. Moreover, localized (31)P spectra showed that occlusion of the
      LAD during AC resulted in severe ischemic changes in the LAD myocardium and the
      abnormal metabolic changes were completely abolished by use of SARC. Finally,
      recovery of myocardial contractile function during reperfusion in the hearts
      subjected to SARC was significantly better compared to those arrested with AC
      alone. It was concluded that the myocardium distal to a coronary occlusion can be
      fully protected by use of SARC.

PMID- 11590655
TI  - Positive effects of polyethylene glycol conjugation to generation-4
      polyamidoamine dendrimers as macromolecular MR contrast agents.
AB  - Macromolecules conjugated with polyethylene glycol (PEG) acquire more
      hydrophilicity, resulting in a longer half-life in circulation and lower
      immunogenicity. Two novel conjugates for MRI contrast agents were synthesized
      from a generation-4 polyamidoamine dendrimer (G4D), 2-(p-isothiocyanatobenzyl)-6
      methyl-diethylenetriaminepentaacetic acid (1B4M), and one or two PEG molecules
      with a molecular weight of 20000 Da (PEG(2)-G4D-(1B4M-Gd)(62) (MW: 96 kD), PEG(1)
      G4D-(1B4M-Gd)(63) (MW: 77 kD)). Their pharmacokinetics, excretion, and properties
      as vascular MRI contrast agents were evaluated and compared with those of G4D
      (1B4M-Gd)(64) (MW: 57 kD). PEG(2)-G4D-(1B4M-Gd)(62) remained in the blood
      significantly longer and accumulated significantly less in the liver and kidney
      than the other two preparations (P < 0.01). Although the blood clearance was
      slower, PEG(2)-G4D-(1B4M-Gd)(62) was excreted more readily without renal
      retention than the other two preparations. In conclusion, the positive effects of
      PEG conjugation on a macromolecular MRI contrast agent were found to be prolonged
      retention in the circulation, increased excretion, and decreased accumulation in
      the organs.

PMID- 11590656
TI  - Direct comparison of 3D spiral vs. Cartesian gradient-echo coronary magnetic
      resonance angiography.
AB  - While 3D thin-slab coronary magnetic resonance angiography (MRA) has
      traditionally been performed using a Cartesian acquisition scheme, spiral k-space
      data acquisition offers several potential advantages. However, these strategies
      have not been directly compared in the same subjects using similar methodologies.
      Thus, in the present study a comparison was made between 3D coronary MRA using
      Cartesian segmented k-space gradient-echo and spiral k-space data acquisition
      schemes. In both approaches the same spatial resolution was used and data were
      acquired during free breathing using navigator gating and prospective slice
      tracking. Magnetization preparation (T(2) preparation and fat suppression) was
      applied to increase the contrast. For spiral imaging two different examinations
      were performed, using one or two spiral interleaves, during each R-R interval.
      Spiral acquisitions were found to be superior to the Cartesian scheme with
      respect to the signal-to-noise ratio (SNR) and contrast-to-noise-ratio (CNR)
      (both P < 0.001) and image quality. The single spiral per R-R interval
      acquisition had the same total scan duration as the Cartesian acquisition, but
      the single spiral had the best image quality and a 2.6-fold increase in SNR. The
      double-interleaf spiral approach showed a 50% reduction in scanning time, a 1.8
      fold increase in SNR, and similar image quality when compared to the standard
      Cartesian approach. Spiral 3D coronary MRA appears to be preferable to the
      Cartesian scheme. The increase in SNR may be "traded" for either shorter scanning
      times using multiple consecutive spiral interleaves, or for enhanced spatial
      resolution.

PMID- 11590657
TI  - Novel liver macromolecular MR contrast agent with a polypropylenimine
      diaminobutyl dendrimer core: comparison to the vascular MR contrast agent with
      the polyamidoamine dendrimer core.
AB  - As MRI contrast agents, more hydrophobic molecules reportedly accumulate in the
      liver and thus are potentially useful as liver MRI contrast agents. In this
      study, a generation-4 polypropylenimine diaminobutane dendrimer (DAB-Am64), which
      is expected to be more hydrophobic than the generation-4 polyamidoamine dendrimer
      (PAMAM-G4D), was used to synthesize a conjugate with 2-(p-isothiocyanatobenzyl)-6
      methyl-diethylenetriaminepentaacetic acid (1B4M) [DAB-Am64-(1B4M-Gd)(64)] for
      complexing Gd(III) ions. This DAB conjugate quickly accumulated in the liver and
      its characteristics were studied and compared with those of a PAMAM conjugate
      [PAMAM-G4D-(1B4M-Gd)(64)], which is known to be a useful vascular MRI contrast
      agent, in regard to its availability as a liver MRI contrast agent. DAB-Am64
      (1B4M-Gd)(64) accumulated significantly more in the liver and less in blood than
      PAMAM-G4D-(1B4M-Gd)(64) (P < 0.001). Contrast-enhanced MRI with DAB-Am64-(1B4M
      Gd)(64) was able to homogeneously enhance liver parenchyma and visualize both
      portal and hepatic veins of 0.5 mm diameter in mice. In conclusion, DAB-Am64
      (1B4M-Gd)(64) is a good candidate for a liver MRI contrast agent.

PMID- 11590658
TI  - Comparison of aerosolized gadoteridol and gadopentetate dimeglumine for magnetic
      resonance ventilation imaging of the lung.
AB  - The purpose of this study was to compare aerosolized gadoteridol and
      gadopentetate dimeglumine in regard to homogeneity of aerosol distribution and
      relative pulmonary signal intensity (SI) changes after a 10-min mechanical
      ventilation period. Twenty experimental procedures were performed in 10 intubated
      domestic pigs that were mechanically aerosolized with the nebulized contrast
      medium. Images were obtained by using a respiratory-gated T(1)-weighted TSE
      sequence. Pulmonary SI increase for the right and left lung was 26% +/- 25% and
      25% +/- 12%, respectively, for gadopentetate dimeglumine, and 45% +/- 12% and 43%
      +/- 10%, respectively, for gadoteridol. Aerosol distribution was rated
      homogeneous in all cases by two readers. It is concluded that both contrast
      agents in aerosolized form are capable of depicting pulmonary ventilation in
      healthy animals with lung capacities comparable to those of humans. SI
      differences between gadoteridol and gadopentetate dimeglumine are explained by
      their considerable difference in viscosity.

PMID- 11590659
TI  - Active acoustic control in gradient coils for MRI.
AB  - The new principles of active acoustic control in gradient coil design recently
      introduced by Mansfield and Haywood (MAGMA 1999;8(Suppl 1):55) are further
      developed theoretically for the far-field acoustic output for a single sector of
      a coil system comprising four or more flat rectangular coil sectors. Each sector
      consists of a split plate arrangement in which are embedded two windings, an
      outer primary winding and a narrow inner re-entrant loop control winding
      immediately adjacent to and surrounding the split or air gap. The wire spacing of
      the control winding is made small so as not to affect substantially the magnetic
      field created by the primary winding. Experimental results are presented for two
      sectors each made of a different readily available plastic material and tested
      over a range of frequencies. They both show substantial average reductions in
      acoustic output over the full output when the control winding is appropriately
      driven. New theoretical expressions are derived for particular frequencies based
      on normal mode expansions for the plate. This new approach is better able to
      explain the acoustic output difference between the full and reduced output modes.
      Empirical expressions are also developed which include longitudinal as well as
      transverse plate characteristics and used to fit the experimental acoustic output
      data as a function of frequency and indicate good agreement with regard to both
      the form and amplitude of the acoustic output response.

PMID- 11590660
TI  - EPR oxygen mapping (EPROM) of engineered cartilage grown in a hollow-fiber
      bioreactor.
AB  - A novel electron paramagnetic resonance (EPR)-based oxygen mapping procedure
      (EPROM) is applied to cartilage grown in a single-, hollow-fiber bioreactor
      (HFBR) system. Chondrocytes harvested from the sterna of 17-day-old chick embryos
      were inoculated into an HFBR and produced hyaline cartilage over a period of 4
      weeks. Tissue oxygen maps were generated according to the EPROM technique (Velan
      et al., Magn Reson Med 2000;43:804-809) by making use of the line-broadening
      effects of oxygen on the signal generated from nitroxide spin probes. In
      addition, the effect on oxygen consumption of the addition of cyanide to the
      tissue was investigated. Cyanide is a potent inhibitor of oxidative
      phosphorylation, and accordingly, given the constant provision of oxygen to the
      tissue, it would be expected to increase oxygen levels within the HFBR. The EPROM
      measurements showed a significant increase in oxygen concentration in the
      cartilage after the addition of cyanide. In contrast to other methods for
      studying oxygen in cartilage, EPROM can provide direct, noninvasive visualization
      of local concentrations in three dimensions.

PMID- 11590661
TI  - A serial MR study of cerebral blood flow changes and lesion development following
      endothelin-1-induced ischemia in rats.
AB  - The vasoconstrictive peptide endothelin-1 (ET-1) has been used previously to
      transiently occlude the middle cerebral artery (MCA) in rats. However, the
      duration of the resulting reduction in cerebral blood flow (CBF) and the
      reperfusion characteristics are poorly understood. In this study perfusion and
      T(2)-weighted MRI were used together with histology to characterize the cerebral
      perfusion dynamics and lesion development following ET-1 injection. Twenty-two
      rats received an intracerebral injection of ET-1 adjacent to the MCA. CBF was
      reduced to 30-50% of control levels, and a significant reduction persisted for 16
      h in the cortex and 7 h in the striatum. The lesion size measured by T(2)
      weighted imaging at 48 h correlated with the final infarct size measured by
      histology at 7 d. The sustained reduction in CBF and the gradual development of
      the ischemic lesion resemble human stroke evolution, suggesting that this model
      may be useful for evaluating therapeutic agents, particularly when treatment is
      delayed.

PMID- 11590662
TI  - Improved spatial harmonic selection for SMASH image reconstructions.
AB  - The fitting of coil sensitivity functions to spatial harmonics is central to
      image reconstructions using the simultaneous acquisition of spatial harmonics
      (SMASH) technique. It has previously been shown that the selection of the set of
      spatial harmonics used in a SMASH reconstruction can have a noticeable effect on
      the quality of the reconstructed image. However, a mechanism for automatic
      selection of the best set of harmonics in any particular situation has not been
      provided. In this work, a modification to the SMASH reconstruction procedure is
      introduced that allows the use of a weighted average of all possible harmonics in
      a reconstruction. The new reconstruction procedure is shown to allow automatic
      selection of the spatial harmonics and substantially improve SNR for both phantom
      and in vivo images.

PMID- 11590663
TI  - Modeling tissues contrast agent concentration: a solution to the tissue
      homogeneity model using a simulated arterial input function.

PMID- 11590665
TI  - Antiviral drugs with extra-cellular sites of action.

PMID- 11590666
TI  - Congenital cataract following German measles in the mother. 1942. [classical
      article].

PMID- 11590667
TI  - Hepatitis B virus (HBV) reactivation after cytotoxic or immunosuppressive therapy
      -pathogenesis and management.
AB  - In an endemic area for chronic hepatitis B infection, reactivation of this virus
      is a serious cause of morbidity and mortality in patients undergoing cytotoxic or
      immunosuppressive therapy. Careful prospective serological testing has shown that
      hepatitis B virus reactivation is a two-staged process. The initial stage occurs
      during intense cytotoxic or immunosuppressive therapy and is characterised by
      enhanced viral replication, as reflected by increases in the serum levels of
      hepatitis B virus DNA, hepatitis B e antigen, hepatitis B virus DNA polymerase
      and infection of naive hepatocytes with hepatitis B virus. The second stage is
      related to restoration of immune function following withdrawal of cytotoxic or
      immunosuppressive therapy, which causes rapid immune-mediated destruction of
      infected hepatocytes. Clinically, this can lead to hepatitis, hepatic failure and
      even death. The occurrence and severity of hepatitis B virus reactivation after
      various cytotoxic or immunosuppressive therapy is unpredictable and treatment has
      been disappointing, largely due to the late administration of therapy. Recently,
      pre-emptive treatment of chronic hepatitis B patients undergoing cytotoxic or
      immunosuppressive therapy, with potent nucleoside analogues has shown some
      promising results. Further controlled studies are needed to define the incidence
      and risk factors of hepatitis B reactivation so that pre-emptive treatment with
      nucleoside analogues could be administered to those patients at high risk of
      disease.

PMID- 11590668
TI  - Dengue fever and dengue haemorrhagic fever: challenges of controlling an enemy
      still at large.
AB  - Dengue virus infections are a serious cause of morbidity and mortality in most
      tropical and subtropical areas of the world: mainly Southeast and South Asia,
      Central and South America, and the Caribbean. Understanding the pathogenesis of
      dengue haemorrhagic fever (DHF), the severe form of dengue illness, is a very
      important and challenging research subject. Viral virulence and immune responses
      have been considered as two major factors responsible for the pathogenesis.
      Virological studies are attempting to define the molecular basis of viral
      virulence. The immunopathological mechanisms appear to include a complex series
      of immune responses. A rapid increase in the levels of cytokines and chemical
      mediators apparently plays a key role in inducing plasma leakage, shock and
      haemorrhagic manifestations. It is likely that the entire process is initiated by
      infection with a so-called virulent dengue virus, often with the help of
      enhancing antibodies in secondary infection, and then triggered by rapidly
      elevated cytokines and chemical mediators produced by intense immune activation.
      However, understanding of the DHF pathogenesis is not complete. We still have a
      long way to go.

PMID- 11590669
TI  - Post-genomic virology: the impact of bioinformatics, microarrays and proteomics
      on investigating host and pathogen interactions.
AB  - Post-genomic research encompasses many diverse aspects of modern science. These
      include the two broad subject areas of computational biology (bioinformatics) and
      functional genomics. Laboratory based functional genomics aims to measure and
      assess either the messenger RNA (mRNA) levels (transcriptome studies) or the
      protein content (proteome studies) of cells and tissues. All of these methods
      have been applied recently to the study of host and pathogen interactions for
      both bacteria and viruses. A basic overview of the technology is given in this
      review together with approaches to data analysis. The wealth of information
      produced from even these preliminary studies has shown the generalities,
      subtleties and specificities of host-pathogen interactions. Such research should
      ultimately result in new methods for diagnosing and treating infectious diseases.

PMID- 11590670
TI  - Towards a human Lassa fever vaccine.
AB  - Arenaviruses, such as Lassa fever, establish chronic infections in rodents,
      leading to incidental transmission to humans. Lassa fever is a clinically severe
      disease, yet the absence of second attacks implies life-long immunity. The aim of
      this review is to consider whether such immunity could be provided by vaccines.
      The South American arenaviruses are controlled by neutralising antibody and a
      clinical trial of live, attenuated vaccine for Argentinian haemorrhagic fever
      provided 84% protection. In contrast, there is no evidence for protective humoral
      immunity against Old World arenaviruses which are controlled by cell-mediated
      immune responses. Nevertheless, vaccination with Lassa glycoproteins can protect
      monkeys from disease, implying that protection may be achievable, even though the
      immunological mechanisms are distinct. Recombinant vaccinia viruses expressing
      various forms of Lassa glycoproteins can protect both guinea-pigs and primates,
      while additional protective responses can be mounted against nucleocapsid genes.
      However, vaccines based upon vaccinia constructs are no longer tenable for
      African populations with a high seroprevalence of HIV infection. The scientific
      challenge now remains to find alternative methods of delivering T-cell immunity
      against glycoproteins from Lassa virus in ways which can overcome the local
      economic and political hurdles to vaccine development.

PMID- 11590672
TI  - Long-term clinical safety and efficacy of NIROYAL vs. NIR intracoronary stent.
AB  - Research in vitro and in animal models suggested that gold electroplating of
      stents can attenuate neointimal hyperplasia and reduce thrombogenicity. The
      objective of this study was to evaluate the safety and efficacy of the gold
      coated NIROYAL stent in the treatment of stenosed coronary arteries and bypass
      grafts. We retrospectively studied 181 consecutive patients undergoing deployment
      of NIR (n = 87) or NIROYAL (n = 94) coronary stents in a single tertiary referral
      center from July 1997 to December 1998. Mean follow-up duration for the NIR and
      NIROYAL patient groups were 11.6 and 11.4 (range, 3-12) months, respectively.
      Stent thrombosis rates were 3/87 (3%) in the NIR and 0/94 (0%) in the NIROYAL
      group (P = 0.07). The need for target lesion revascularization (TLR) in the NIR
      patient group was 8/87 (9%) compared to 11/94 (12%) in the NIROYAL patient group
      (P = 0.6). The overall MACE rates for the NIR and NIROYAL patient groups were
      24/87 (28%) and 22/94 (23%), respectively (P = 0.5). The present study, hence,
      implies equivalence between the stainless steel NIR and the gold-plated NIROYAL
      stent with no significant difference in immediate and long-term clinical
      performance profiles.

PMID- 11590673
TI  - Safety and efficacy of suture-mediated closure after percutaneous coronary
      interventions.
AB  - Percutaneous coronary interventions (PCI) performed with concomitant use of
      heparin and platelet inhibitors are safe procedures with reported vascular
      complication rates of approximately 6.1%. EPILOG investigators demonstrated that
      utilizing a low-dose heparin regimen with abciximab, along with early sheath
      removal, vascular access-related bleeding was significantly lower than that
      reported in EPIC. Recently, a suture-mediated closure (SMC) device has been
      reported to be safe, appears effective, and may improve patient comfort by
      allowing early ambulation. We conducted a retrospective analysis (January 1999 to
      March 2000) of complication frequencies among PCI patients who underwent SMC and
      those who had manual compression (non-SMC). Furthermore, we compared the overall
      rates of complications to patients who underwent PCI prior to the introduction of
      SMC (1995-1998). When comparing the current cohort to the historical cohort,
      there was a significant decrease in the number of retroperitoneal bleeds (0.3%
      vs. 0.9%; P = 0.003), hematomas (5% vs. 9%; P < 0.001), pseudoaneurysms (1.2% vs.
      2.7%; P < 0.001), and need for vascular surgery (0.9% vs. 2.8%; P < 0.001). There
      was no difference in the number of arterio-venous fistulas and a slight increase
      in transfusion needs (12% vs. 10%; P = 0.03). Within the current cohort, there
      was no difference in the vascular complications between SMC and non-SMC PCI
      patients, although there were lower rates of pseudoaneurysms (0.5% vs. 1.8%; P =
      0.02) and transfusion requirements (72/880 vs. 132/874; P < 0.001). These results
      suggest that the complication rates for SMC are not different and may be lower
      when compared to non-SMC patients after PCI. At our institution, the practice of
      early sheath removal and less aggressive heparin dosing has led to a decrease in
      vascular complication rates and a 66% reduction in vascular surgeries on post-PCI
      patients. Because of the limitations of retrospective analyses, further studies
      will be necessary to confirm these findings.

PMID- 11590674
TI  - A comparison of total hospital costs for percutaneous coronary intervention
      patients receiving abciximab versus tirofiban.
AB  - The purpose of this study was to examine the total hospital costs associated with
      the receipt of abciximab versus tirofiban for percutaneous coronary intervention
      (PCI) patients. Hospital billing data for patients with a primary procedure of
      PCI was examined for the period of July 1998 to June 1999 from HCIA-Sach's
      Clinical Pathways Database. Data were analyzed for all patient discharges whose
      records indicated use of abciximab or tirofiban with a PCI. Results are reported
      for 3,967 patients. Multivariate analysis was used to control for a wide range of
      factors (GP IIb/IIIa selection, patient demographics, stent use, insurance type,
      health conditions, admission information, and hospital characteristics) that may
      influence the cost of hospitalization. A two-stage sample selection model was
      used to estimate total costs. The first stage of the analysis utilizes a probit
      regression to determine the factors associated with the likelihood of receiving
      abciximab versus tirofiban. The second stage of the analysis examines the factors
      associated with total hospital costs, while controlling for unobserved factors
      that may be correlated with the patient's likelihood of receiving abciximab. The
      mean unadjusted cost per hospitalization, including drug costs, was $10,762
      (abciximab $10,813 and tirofiban $10,567). After controlling for high-risk
      indications and selection bias with the two-stage sample selection model, results
      indicate there was no significant difference in costs associated with the receipt
      of abciximab versus tirofiban. However, the results also indicate that the two
      stage sample selection model may not be needed (lambda was not statistically
      significant) hence, the cost equation was reestimated using ordinary least
      squares methodology (OLS). In the OLS analysis, receipt of abciximab versus
      tirofiban was associated with a significant reduction in costs ($470 reduction; P
      = 0.05). This study uses real-world data to examine the total hospital costs for
      PCI patients who receive abciximab versus tirofiban. Results of the two-stage
      sample selection model indicate there is no difference in total hospital costs
      (including drug costs) between abciximab- and tirofiban-treated patients. If the
      results of the OLS model are considered, a slight decrease in total hospital
      costs is observed in abciximab recipients. Cost-containment strategies that focus
      on component costs may not lead to intended overall cost savings.

PMID- 11590675
TI  - Direct coronary stenting without balloon or device pretreatment: acute success
      and long-term results.
AB  - Improvements in coronary stents have made planned direct coronary stenting
      technically feasible, though safety, acute success, cost-effectiveness, and long
      term results remain to be determined. Sequential patients eligible for direct
      stenting were prospectively characterized and treated with either direct or
      secondary stenting. Major adverse cardiovascular events (MACE) such as cardiac
      death, myocardial infarction (MI), target vessel ischemia, or revascularization
      (TVR) were followed for 6 months post-PCI. Enrollment included 128 direct (1.38
      lesions/patient) and 69 secondary (1.39 lesions/patient) stented patients. Direct
      stenting was successful in 99% (with 5% crossover to secondary stenting) without
      major procedural complications and with a similar rate of vessel wall dissection
      or no-reflow phenomenon (2.3% vs. 2.1%; P > 0.05) as the secondary stenting
      group. There was a trend toward less postprocedural CPK-MB elevation in the
      nonacute MI patients with direct vs. secondary stenting (3% vs. 11%,
      respectively). At 6 months, there were no statistically significant differences
      in overall MACE. Direct stenting has a high success rate, low complication rate,
      and durable long-term results. Procedural cost and time savings, less contrast
      use and radiation exposure make direct stenting attractive in properly selected
      patients.

PMID- 11590676
TI  - Should every eligible lesion undergo direct stenting?

PMID- 11590677
TI  - Efficacy and safety of PTCA using brachial approach and low-dose heparin.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) is routinely performed
      using the femoral approach. However, recent reports suggest the usefulness of the
      brachial approaches for patients for whom the femoral approach is impossible due
      to peripheral vessel disease or to shortened postoperative rest times. However,
      some reports have revealed that the incidence of vascular complications
      undergoing brachial-approach PTCA may be higher than those with the femoral
      approach, possibly due to relatively higher dose of heparin. Accordingly, in this
      study we evaluated the efficacy and safety of PTCA using the brachial approach
      and low-dose heparin, hypothesizing that lowering the heparin dose might result
      in reduced vascular complications. The study population of patients admitted for
      angina pectoris consisted of 217 subjects (221 lesions) who underwent brachial
      approach PTCA and 102 subjects (115 lesions) who underwent PTCA via the femoral
      approach. Both groups were monitored for complications. There were no significant
      differences in patient or lesion characteristics between the groups. Incidence of
      vascular complications tended to be lower in the brachial group than in the
      femoral group (1.8% vs. 3.5%), although the difference did not reach statistical
      significance. Use of anodynes was also significantly lower in the brachial group
      (3.6% vs. 33%). PTCA from the brachial approach with low-dose heparin is as safe
      and effective a strategy as compared with the femoral approach with standard dose
      of heparin.

PMID- 11590678
TI  - Intravascular ultrasound analysis of beta radiation therapy for diffuse in-stent
      restenosis to inhibit intimal hyperplasia.
AB  - We evaluated the efficacy of beta-radiation therapy ((188)Re-MAG(3)) to inhibit
      intimal hyperplasia (IH) in diffuse in-stent restenosis by intravascular
      ultrasound (IVUS) analysis in 50 patients. Nine patients who did not agree with
      radiation therapy, and therefore underwent rotational atherectomy and balloon
      angioplasty for diffuse in-stent restenosis in the same study period, were
      selected for control groups. Serial IVUS comparisons were available in 44 of 50
      patients with radiation therapy and 7 of 9 control patients. At 6-month follow
      up, there was less significant increase of IH area in patients with radiation
      therapy than in control patients (Delta IH area = 0.1 +/- 0.8 mm(2) vs. 2.6 +/-
      1.8 mm(2), P > 0.001 in mean values, and 0.6 +/- 1.4 mm(2) vs. 2.9 +/- 2.1 mm(2),
      P = 0.026 in values of follow-up lesion site, respectively). In conclusion, beta
      radiation therapy might be an effective treatment modality to inhibit intimal
      hyperplasia in patients with diffuse in-stent restenosis.

PMID- 11590679
TI  - The elective use of the seven-cell NIR stent in coronary arteries < 2.75 mm in
      diameter: clinical and angiographic results at 6-month follow-up.
AB  - The outcome of interventional procedures has been improved by the use of coronary
      stents in vessels > 3.0 mm in diameter. We report a single-center prospective
      study of elective coronary stenting in 39 consecutive patients with de novo
      lesions and reference diameters < 2.75 mm. Seven-cell NIR stents were deployed
      with standard antiplatelet therapy, but without routine use of IIb/IIIa
      inhibitors or intravascular ultrasound. There was one case of acute stent
      thrombosis, but no cases of subacute thrombosis. The binary restenosis rate was
      27.8% (10/36 lesions) and the target lesion revascularization rate was 19.4%.
      Symptoms improved markedly as judged by Canadian Cardiovascular Society and
      questionnaire scores and the use of antianginal therapy. This pilot study
      suggests that the elective use of coronary stents in vessels < 2.75 mm in
      diameter is safe with acceptable long-term results. A randomized trial comparing
      outcomes after stents and balloon angioplasty in small vessels is required.

PMID- 11590680
TI  - Initial experience and safety in the treatment of chronic total occlusions with
      fiberoptic guidance technology: optical coherent reflectometry.
AB  - Percutaneous treatment of chronic total coronary occlusions has been limited by
      procedural complications such as vessel injury or perforation. Optimizing
      visualization in the vessel with optical coherent reflectometry and a forward
      looking fiberoptic guidance technology may improve the safety and efficacy of
      percutaneous treatment of these lesions.

PMID- 11590681
TI  - Safety and efficacy of repeat transradial access for cardiac catheterization
      procedures.
AB  - To determine the safety and efficacy of repeat transradial cardiac
      catheterization, 1,362 consecutive transradial procedures were examined. Repeat
      transradial procedures were identified (group I, n = 73) and compared with index
      procedures (group II, n = 1,289). Baseline patient characteristics, procedure
      success rates (100% vs. 97.9%; P = NS), complication rates (0% vs. 0.08%; P =
      NS), and procedure times (23.9 +/- 27.3 min vs. 18.2 +/- 14.7 min; P = NS) were
      similar between groups. This study suggests that repeat transradial
      catheterization procedures can be performed safely and successfully in
      appropriately selected patients.

PMID- 11590682
TI  - Activated clotting time as a screening test prior to catheter-based
      cardiovascular procedures.
AB  - The activated clotting time (ACT) was investigated as a rapid, inexpensive, point
      of-service screening test for coagulation abnormalities prior to catheter-based
      procedures. A total of 963 patients were screened by obtaining a history,
      standard coagulation profile, and activated coagulation time. The prevalence of
      normal patients (normal ACT and coagulation profile) was 94% (sensitivity = 91%;
      specificity = 27%). A normal ACT had a positive predictive value of 95%. The ACT
      was an acceptable screening test due to its ability to predict positively a low
      rate of bleeding complication and normal coagulation studies. Patients with ACT >
      150 sec should be further evaluated with a screening coagulation panel.
      Additionally, given its low specificity, coagulation studies should be obtained
      in high-risk patients since an abnormal ACT does not effectively correlate with
      abnormal coagulation studies.

PMID- 11590683
TI  - The problem of arteria lusoria in right transradial coronary angiography and
      angioplasty.
AB  - The retroesophageal right subclavian artery (arteria lusoria) is one of the
      anatomical abnormalities encountered by interventional cardiologists who perform
      right transradial procedures. We report on 11 patients with arteria lusoria in
      whom 14 right transradial coronary angiography or angioplasty procedures were
      attempted among a series of 3,730 consecutive right transradial attempts. This
      abnormality can be easily detected by angiographic visualization, in the
      anteroposterior projection, of the angle of the catheter when it engages the
      ascending aorta, and by manual angiography at the ostium of the right subclavian
      artery. In such a case, catheterization of the ascending aorta may be difficult
      or even impossible (7.1%). Selective catheterization of both coronary arteries is
      more difficult, takes longer, and requires more catheters. The Judkins catheters
      are recommended, although they are seldom used for the left coronary artery via
      the right radial approach, for both arteries. All catheter exchanges should be
      performed on long guidewires.

PMID- 11590684
TI  - The many faces of the anomalous left aortic arch.

PMID- 11590685
TI  - Limitations of successive transradial approach in the same arm: the Japanese
      experience.
AB  - The transradial approach (TRA) has been used for diagnostic and interventional
      cardiology. It has not previously been determined how many times the same radial
      artery can be cannulated without complications. A total of 812 patients (502 men
      and 310 women) underwent angiography or angioplasty via the TRA between 1997 and
      1999 at our institution with a total of 1,438 procedures. Sheaths were 5 (55%) or
      6 Fr (45%). Dropout rates of 3.5% and 7.9% were found at the second TRA attempt
      in the men and the women, respectively. Of the 62 TRA failures, 56 (90%) were due
      to narrowing or occlusion of the radial artery after the previous TRA procedure.
      A third TRA procedure was possible in 90% of the men and 80% of the women. A
      fifth TRA procedure was possible in 70% of the men and 50% of the women. The
      dropout rates for TRA increased as successive punctures were performed. This was
      primarily due to vessel narrowing and occlusion occurring as a function of
      multiple punctures.

PMID- 11590686
TI  - Successful closure of coronary artery perforation using makeshift stent sandwich.
AB  - An elderly woman underwent stenting of mid left anterior descending coronary
      artery (LAD) 2 days after myocardial infarction. During high-pressure stent
      dilatation, vessel perforation was noted. We assembled a "stent sandwich" in the
      cardiac catheterization laboratory and used it successfully to seal the
      perforation with good angiographic result. Although the long-term patency remains
      an issue, this case demonstrates the feasibility of using makeshift covered-stent
      as a bailout for arterial perforation in selected cases where emergency
      thoracotomy is undesirable.

PMID- 11590687
TI  - Perspectives on makeshift modalities for treatment of coronary perforation.

PMID- 11590688
TI  - Late acute thrombosis after coronary brachytherapy: when is the risk over?
AB  - Late total occlusion (LTO) after simultaneous coronary stenting and brachytherapy
      has been described in recent randomized trials. We report a case of LTO
      presenting with an acute clinical event 15 months after the index procedure,
      suggesting that the risk is not confined to the first 6-month to 1-year period.

PMID- 11590689
TI  - Radiation and late thrombosis: issues, facts, and solutions.

PMID- 11590690
TI  - Abciximab for the treatment of acute distal embolization associated with internal
      carotid artery angioplasty.
AB  - Carotid artery angioplasty and stent placement (CAS) can be complicated by
      procedure-related distal embolization and thrombus formation, potentially
      resulting in neurological sequelae. Patient A had CAS of left internal carotid
      artery and had loss of vision in the left eye with no flow in the left ophthalmic
      artery. Patient B had CAS of right internal carotid artery and developed left
      sided hemiparesis with total occlusion of the right middle cerebral artery. A
      selective intra-arterial injection of 5 mg of abciximab locally followed by a
      bolus of 5 mg of abciximab intravenously resulted in complete resolution of the
      filling defect on repeat angiography after 10 min in both patients.

PMID- 11590691
TI  - Closure of prosthetic paravalvular mitral regurgitation with the Gianturco-Grifka
      vascular occlusion device.
AB  - Paravalvular regurgitation associated with prothetic mitral valves is often a
      consequence of infectious endocarditis. The condition is usually treated with
      debridement and repeat surgical valve replacement. However, repeated operations
      are associated with high risk. This report describes a case of successful
      transcatheter treatment of severe paravalvular mitral regurgitation and pulmonary
      edema in a patient in whom repeat mitral valve replacement was not believed
      possible.

PMID- 11590692
TI  - Stent implantation for aortic coarctation complicating the Norwood operation in a
      48-day-old baby.
AB  - A female infant developed severe aortic coarctation 42 days after a Norwood
      operation. Balloon dilatation was ineffective due to rapid recoil of the
      narrowing, but stent implantation completely abolished coarctation. Although the
      patient died because of low systemic output with high pulmonary flow 62 days
      after stent implantation, an autopsy showed that the implanted stent was widely
      patent without any restenosis. Transcatheter stent implantation should be
      considered for coarctation in selected situations even in early infancy.

PMID- 11590693
TI  - Sequential implantation of two Helex septal occluder devices in a patient with
      complex atrial septal anatomy.
AB  - We report the first implantation of two Helex septal occluder devices in a 10
      year-old boy with complex atrial septal anatomy. The unique characteristics of
      this new device are discussed in the following case report.

PMID- 11590694
TI  - Local delivery of c-myc neutrally charged antisense oligonucleotides with
      transport catheter inhibits myointimal hyperplasia and positively affects
      vascular remodeling in the rabbit balloon injury model.
AB  - Myointimal hyperplasia after percutaneous transluminal coronary angioplasty
      (PTCA) is a key component of the process of restenosis. The c-myc is a critical
      cell-cycle division protein involved in the formation of neointima. We evaluated
      the long-term impact of local delivery of c-myc neutrally charged antisense
      oligonucleotides (Resten-NG) on myointimal hyperplasia after PTCA in a rabbit
      model. PTCA was performed in the iliac arteries of 25 New Zealand white rabbits,
      using a Transport catheter at 8 atm for 30 sec, three times; 500 microg Resten-NG
      (n = 11) or saline (n = 14) was delivered to the PTCA site at 2 atm with the
      outer balloon for 2 min. The diet was supplemented with 0.25% cholesterol for 10
      days before and 60 days after PTCA. Angiography was performed at harvest, and
      vessels were fixed in formalin, processed, and stained with hematoxylin and eosin
      (H&E) and Movat. Quantitative angiography showed that local delivery of antisense
      c-myc at PTCA reduced late luminal loss from 1.8 +/- 0.30 mm in control animals
      to 0.90 +/- 0.30 mm in the treatment group (P = 0.001). Histological analysis by
      planimetry showed that intimal areas were 1.67 +/- 0.44 mm(2) and 0.82 +/- 0.32
      mm(2) in the control and antisense delivery groups, respectively (P < 0.05). We
      conclude that local delivery of Resten-NG inhibited myointimal hyperplasia after
      PTCA in cholesterol-fed rabbits for up to 60 days.

PMID- 11590695
TI  - Optical coherent reflectometry: a new technique to guide invasive procedures.
AB  - The success rate of percutaneous transluminal coronary angioplasty for chronic
      total arterial occlusions is still unsatisfactory. Inability to cross the lesion
      with a guidewire is a major cause of failure. Optical coherent reflectometry
      (OCR) is a new method of using laser light to measure the depth of tissue from
      the end of an optic fiber. This study tests whether an OCR prototype guidewire
      provides a guidance system that might be useful to assist reopening chronic total
      arterial occlusions. An OCR fiber optic within a 0.014" hypotube was developed
      using the interference pattern of two reflected light beams (wave length 1,300
      nm). To determine if OCR can distinguish different tissue types, plaques of human
      lower extremity arterial segments were visually divided into three types
      (calcified, white, or yellow). The slope of the initial reflectance of the OCR
      curve was calculated and compared between the three groups. In six other
      arteries, the OCR wire was advanced longitudinally through occluded human artery
      segments in vitro. Guidewire position was determined by OCR and compared to the
      position of the guidewire tip observed simultaneously by intravascular ultrasound
      (IVUS) imaging. In 16 arterial surface segments, calcified plaques had a
      significantly steeper slope than white or yellow plaques (-227.2 +/- 82.2; -81.5
      +/- 12.9; -103.6 +/- 19.6 dB/mm; P < 0.01). For the determination of the
      guidewire position, IVUS and OCR corresponded correctly in 82% of 28
      measurements. Sensitivity and specificity of OCR for detection of plaque versus
      the media/adventitia boundary were 79% and 89%, respectively (P < 0.001). OCR can
      distinguish calcified from noncalcified plaque and may distinguish plaque from
      the media/adventitia boundary. This technology may be useful as a means to help
      navigate a guidewire safely through an occluded artery.

PMID- 11590696
TI  - Across the great divide.

PMID- 11590698
TI  - Use of intracoronary adenosine for the management of slow-no-reflow phenomenon
      during percutaneous interventions.

PMID- 11590700
TI  - Selective activity of butyrylcholinesterase in serum by a chemiluminescent assay.
AB  - In a previous study, we showed that purified commercial esterase activity can be
      detected in a chemiluminescent assay based on the hydrolysis of 2-methyl-1
      propenylbenzoate (MPB) to 2-methyl-1-propenol, which is subsequently oxidized by
      the horseradish peroxidase (HRP)-H(2)O(2) system. The purpose of this study was
      to verify the applicability of this assay to human serum. The existence of an
      esterase activity capable of hydrolysing MPB is indicated by the fact that the
      MPB-serum-HRP-H(2)O(2) system consumes oxygen and emits light. Both signals were
      abolished by prior serum heat inactivation and were preserved when serum was
      stored at < or =4 degrees C. Addition of aliesterase inhibitors, such as fluoride
      ion and trichlorfon or the cholinesterase inhibitor eserine, totally prevents
      light emission. The butyrylcholinesterase-specific substrate benzoylcholine
      causes a delay in both O(2) uptake and light emission, while the specific
      acetylcholinesterase substrate, acetyl-beta-methylcholine, had practically no
      effect. Purified butyrylcholinesterase, but not acetylcholinesterase, triggered
      light emission. The finding that butyrylcholinesterase is responsible for the
      hydrolysis of MPB in serum should serve as the basis for the development of a
      specific chemiluminescent assay for this enzyme.

PMID- 11590701
TI  - Direct enzymatic reduction of lucigenin decreases lucigenin-amplified
      chemiluminescence produced by superoxide ion.
AB  - The interaction of superoxide ion with lucigenin produces chemiluminescence (CL),
      which is widely used for the detection of this radical anion. However, in many
      biological systems lucigenin may be directly reduced to its semiquinone by some
      enzymes. We found that if the direct reduction of lucigenin takes place, it
      decreases superoxide production due to the competition with one-electron
      reduction of dioxygen to superoxide ion. Comparison of two methods of superoxide
      detection (lucigenin-amplified CL and cytochrome c reduction) showed that there
      are excellent correlations between the results obtained by the two methods.
      Hence, lucigenin-amplified CL remains a sensitive and reliable assay of
      superoxide detection.

PMID- 11590702
TI  - Increase in the intensity of thermoluminescence Q-band during leaf ageing is due
      to a block in the electron transfer from Q( A) to Q( B).
AB  - The thermoluminescence (TL) parameters in intact leaves and thylakoids isolated
      from leaves showed a different pattern of change during leaf ageing. Ageing of
      leaves brought about a decrease in the B-band and a simultaneous increase in the
      Q-band. Thylakoids showed only a decrease in the B-band. The TL bands further
      show that there is generation of an endogenous electron transport inhibitor
      during leaf ageing.

PMID- 11590703
TI  - Effect of aqueous cigarette smoke extract on the chemiluminescence kinetics of
      polymorphonuclear leukocytes and on their glycolytic and phagocytic activity.
AB  - Water-soluble extracts of cigarette smoke are easily formed in some body
      compartments, such as saliva or fluid lining alveolar spaces, and can act on both
      cellular and extracellular compartments. In this paper we have analysed the
      effect of aqueous smoke extract on some metabolic and functional aspects of
      polymorphonuclear leukocytes. In particular, the following cellular aspects were
      studied: chemiluminescence, glycolysis, membrane fluidity and microscopic
      interaction with zymosan particles. While chemiluminescence and glycolytic
      activity are highly inhibited, no effect of smoke extract on membrane fluidity
      was observed. Moreover, the response of luminol-dependent chemiluminescence was
      significantly delayed, while that of lucigenin-dependent chemiluminescence was
      anticipated. Furthermore, the phagocytic ability of neutrophils pretreated with
      aqueous smoke extract was also significantly hindered. All these results might
      indicate that the finely tuned activity of polymorphonuclear leukocytes is
      somehow hampered by the aqueous extract of cigarette smoke in a way which makes
      these cells less effective against bacteria and more noxious towards surrounding
      tissues.

PMID- 11590704
TI  - Spontaneous urinary chemiluminescence and diet. An intervention study in humans.
AB  - Spontaneous urinary visible chemiluminiscence has been measured in samples from a
      diet intervention study in humans. For a month, two groups, each of 21 male
      volunteers, received either a Mediterranean-type diet or an occidental (high-fat)
      diet. Urinary chemiluminescence levels (in 10(3) cpm) were 8.5 +/- 3.1 and 6.0 +/
      2.0 for the high-fat and Mediterranean-type diets, respectively. The differences
      obtained were statistically significant. These results reflect differences in the
      oxidative stress associate to both diets and support the proposal that
      spontaneous urinary chemiluminiscence constitutes a complementary index of
      systemic oxidative stress.

PMID- 11590705
TI  - Imaging of hydroperoxide and hydrogen peroxide-scavenging substances by photon
      emission.
AB  - An imaging system for the hydroperoxide and hydrogen donor was developed by
      photon emission from the reactive oxygen species-hydrogen donor-KHCO(3)-MeCHO
      system. Photon intensity (luminance, cd/m(2)) showed a linear correlation with
      the concentration of some hydroperoxides [hydrogen peroxide (H(2)O(2)), tert
      butyl hydroperoxide and methyl ethyl ketone peroxide] and that of hydrogen donors
      (catechins and anthocyanins). The linear relationship between photon intensity
      and concentration was observed in polyphenol-rich samples, such as teas, berries
      and currants. Photon intensity from the H(2)O(2)/polyphenol-rich sample-KHCO(3)
      MeCHO system corresponded with H(2)O(2)-scavenging activity, rather than with
      polyphenol contents. It is possible to classify hydrogen donor species according
      to absorption features using spectral analysis (gallic acid, E(max) 645 nm,
      catechins, E(max) 610 nm; anthocyanins, E(max) 690-700 nm). This method is a
      simple and sensitive detection system for hydroperoxide- and H(2)O(2)-scavenging
      substances.

PMID- 11590706
TI  - Effect of the geometry of microfabricated flow reactors on chemiluminescent
      detection of epinephrine with lucigenin.
AB  - Three types of flow reactors with different lengths (12-126 mm) and widths (0.4
      2.0 mm) of channel were made on the silicon chip by microfabrication techniques
      for the chemiluminescent (CL) detection of epinephrine (EP) with lucigenin (Luc).
      The volume of each CL reactor was about 10 microL. A solution containing EP and
      Luc and a solution containing NaOH and periodate were injected successively into
      each inlet of the CL reactor in the range 20-100 microL/min with a pressure
      driven flow system. The intensity of light emission was dependent on the geometry
      of the flow reactors. These results could be explained in terms of the
      differences in the diffusion length of the reactants in the flow reactors. The
      maximum light emission were linearly correlated, with the concentrations of EP
      over the range from the detection limit of 5.0 x 10(-8) mol/L up to 5.0 x 10(-6)
      mol/L on the use of the CL reactor with the most promising geometry.

PMID- 11590707
TI  - [Dental knowledge and evaluation of school dental care by school graduates in
      Berne canton].
AB  - In 1996, a letter was written to 401 High-School level graduates of 20 randomly
      selected schools in the canton of Berne, Switzerland. Out of these 401, 343
      individuals could be interviewed and subsequently be given a clinical examination
      comprising a plaque revealing test. The average plaque index was 70%. The
      assessment of the questionnaires showed a comprehensive basic dental knowledge of
      the students so that reasonable care of their teeth could be expected. Whereas
      almost everyone used a toothbrush regularly, flossing fell short in the majority
      of the cases. Outside the class-rooms, concentrated F-preparations were hardly
      used systematically. Besides parents and the family, dentists and specifically
      trained auxiliaries (school dental health assistants, SDHA) were found to play a
      central role in the mediation of theoretical knowledge and in the practical
      instruction of oral hygiene procedures. They received mostly good grades by the
      students for their work. The regular teaching staff, however, fell clearly behind
      the SDHAs. In spite of the obviously big influence on the youth, the dentists
      play only an insignificant role in some places. Overall, the students consider
      dental health education as relatively important placing it on the same level as
      sex education. Since SDHAs do not visit the classes during the last five years
      any longer, teaching of dental prophylaxis has been reduced in many communities
      to fluoridation with concentrated F-preparations. Negative consequences such as
      uncertainty regarding tooth brushing techniques, handling dental floss and
      questions as to oral hygiene behavior after leaving school have already been
      registered. With the academic year 2000/01 one visit by an SDHA to the upper
      level classes (last five years) was reintroduced. This tepid reaction by the
      Bernese education authority to a massive weakening of public dental health
      promotion will hardly suffice to keep up the remarkable level of dental
      prevention reached over the past decades, let alone to warrant substantial
      progress. The study has also demonstrated that the acquisition of knowledge is
      based on repetitive efforts. This is the fundamental reason for systematic
      monitoring and re-instruction of dental hygiene procedures also during the last
      five classes of mandatory scholarity.

PMID- 11590708
TI  - Characteristics of urban ozone level in Hong Kong.
AB  - The long term trend of ozone level in Hong Kong has been investigated. One of the
      characteristics of ozone level in Hong Kong is the existence of autumn maximum
      and summer minimum. Observations of the diurnal variation of ozone level have
      been made in different area categories. There are early morning peak and
      afternoon peak occurred in the diurnal variation, which are different from some
      metropolitans where only an afternoon peak is observed. A negative correlation
      coefficient was found between monthly ozone level with nitric oxide level. On the
      contrary, there is a positive correlation between ozone and nitrogen dioxide. The
      positive correlation coefficient between nitric oxide and nitrogen dioxide shows
      that the total amount of nitric oxide emitted from a series of moving and fixed
      sources greatly exceeded the stoichiometric amount of ozone formed from chemical
      reactions of precursors and long distance transportation.

PMID- 11590709
TI  - Oxidation rate in the preparation of polyferric sulfate coagulant.
AB  - The oxidation rate of ferrous sulfate was investigated in the preparation of
      polyferric sulfate(PFS) coagulant. It was proved that this reaction is zero order
      with respect to Fe2+, first order with respect to NO2(g) and first order with
      respect to the interface area between gas phase and liquid phase. If the partial
      pressure of NO2(g) in gas phase is increased or the interface area is increased,
      the time needed to complete the reaction will be decreased.

PMID- 11590710
TI  - Distribution of aluminum species and the characteristics of structure of poly
      aluminum-chloride-sulfate(PACS).
AB  - A series of poly-aluminum-chloride-sulfate (PACS), which has different basicities
      (gamma) and Al3+/SO4(2-) molar ratio, has been prepared and dried at 105 degrees
      C and 65 degrees C, respectively. The distribution of aluminum species of PACS
      was examined, and the effect of gamma value, Al3+/SO4(2-) molar ratio, dilution
      on the distribution of aluminum species of PACS was also investigated by using
      Alferron timed complex colorimetric method. The IR spectroscopy and X-ray
      diffraction were used to study the effect of gamma value, Al3+/SO4(2-) molar
      ratio and the drying temperature on the structure of PACS. The experimental
      results show that Al3+/SO4(2-) molar ratio has a great effect on the distribution
      of aluminum species, but the dilution has a little effect on the distribution of
      aluminum species. The lower the Al3+/SO4(2-) molar ratio, the higher the
      proportions of the polymer and colloidal species in PACS. The polymeric degree of
      PACS was related to gamma value and Al3+/SO4(2-) molar ratio. Drying temperature
      has an influence on the structure and the solubility of solid PACS products.

PMID- 11590711
TI  - Elemental analysis of some Egyptian ores and industrial iron samples by neutron
      activation analysis.
AB  - Elemental analysis of iron ore samples and first industrial iron production
      prepared by the Egyptian Iron and Steel Company of Helwan near Cairo were
      determined by instrumental neutron activation analysis technique. Five samples
      from each kind were irradiated for a 48 hours at a thermal neutron flux of 4 x
      10(12) n/(cm2.s) in the first Egyptian research reactor ET-RR-1. Also the
      Pneumatic irradiation Rabbit system (PIRS) attached to the reactor in Inshass,
      was used to measure the elements of short-life time. The gamma-ray spectra were
      recorded by means of the hyper pure germanium detection system. The concentration
      percentage values of major, minor and trace elements are presented. The long and
      short lived isotopes were considered. A comparative study and a discussion on the
      elemental concentration values are given.

PMID- 11590712
TI  - Concentrative phenomenon of relative content ratios of Cu, Pb and Zn in soils.
AB  - It is discovered that there is the concentrative phenomenon of relative content
      ratios of Cu, Pb and Zn in soil by studying their parageneous association in
      soil, meteorites and rocks with the relative content ratios. This not only is
      helpful to understand the trends of Cu, Cd and Zn enriched and dispersed in the
      evolution course of earth matter, but also provides evidence for geochemical self
      organization that there may be in the process of Cu, Pb and Zn translation and
      distribution.

PMID- 11590713
TI  - Environmental regulatory and policy framework in China: an overview.
AB  - China has developed one of the most comprehensive environmental regulatory and
      policy framework in the world. This paper provides a description of the main
      institutions for environmental management in China, and overviews the regulatory
      and policy framework in place.

PMID- 11590714
TI  - Climate controls on dust storm occurrence in Maowusu Desert, Inner Mongolia,
      north China.
AB  - Dust storms occurring in arid and semi-arid regions play a main role in the
      evolution of landscapes. Climate is generally regarded to be important factors
      influencing the occurrence of dust storm, however, the way of climate controlling
      dust storms had been poorly understood. In this paper, we present the Ew Index
      model to describe the relationship between climate variables and dust storm
      frequency using the available meteorological data from three meteorological
      stations in Maowusu Desert. This index model explains 83.6%, 69.5% and 65.09% of
      the variance of dust storm frequency in three regions from the north to the
      south, respectively and this difference is probably caused by the difference of
      the human disturbance. The Ew Index model is an effective predictor of dust storm
      frequency and provides us a quite good understanding on the occurrence of dust
      storms in Maowusu Desert.

PMID- 11590715
TI  - An application of a simple computer program for neutron activation analysis.
AB  - A simple computer program is designed for estimation of elemental concentration
      values in complex samples by neutron activation analysis technique. The program
      is applied for an Egyptian cement sample which irradiated at the Egyptian
      Research Reactor-1(ET-RR-1). The data obtained is compared with the reported
      values. The time consumed for such calculations has a remarkable reduction in
      comparison with the routine work.

PMID- 11590716
TI  - Advanced analytical determination of volatile organic compounds (VOC) and other
      major contaminants in water samples using GC-ion trap MS.
AB  - The GC-Ion Trap MS is recently one of the most efficient instrumental analysis
      recommended for understanding the chemistry of volatile organic compounds, not
      only in water but even in the food chain and other environmental media (air and
      soil). Results of the experiment conducted on water samples from Kuguri and
      Yatsutani sampling stations showed considerably higher levels of organic
      enrichment (COD = 10 mg/L and 11 mg/L respectively). Total concentrations of Pb
      (0.072 mg/L and 0.093 mg/L) and Cd (0.004 mg/L and 0.011 mg/L) on the other hand,
      invariably exceeded the maximum allowable concentrations for human health and the
      living environment (Pb = 0.005 mg/L; Cd = 0.001 mg/L respectively). And the
      toxicity levels for these contaminants at LC50 showed critical impact on rainbow
      trout (hypersensitive species) at 0.14 mg/L for Pb and 0.007 mg/L for Cd in 96
      hours respectively. Although these major contaminants including phenol and 3-, 4
      cresol, showed relatively higher toxicity impact in the experimental media, it
      would remain contentious to justify any associated potential dangers without
      regular routine water monitoring, at least for a period of one year.
      Nevertheless, the data could serve as a benchmark through which other phenomena
      can easily be investigated.

PMID- 11590717
TI  - Adsorption of chloroacetanilide herbicides on soil (I). Structural influence of
      chloroacetanilide herbicide for their adsorption on soils and its components.
AB  - Adsorption of chloroacetanilide herbicide acetochlor, alachlor, metolachlor and
      propachlor on soils and soil components was determined, and the structural
      differences of these herbicides were used to explain the order of sorptivity.
      Adsorption isotherms for all herbicide-soil combinations conformed to the
      Freundlich equation, and Ki increased with increasing soil organic carbon
      content. Kd on soil humic acid was greater than that on clay, but association of
      humic acid with clay reduced the overall adsorption. On all soils and soil humic
      acids, herbicide adsorption decreased in the order: metolachlor > acetochlor >
      propachlor > alachlor. On Ca(2+)-montmorrilonite, the order changed to
      metolachlor > acetochlor > alachlor > propachlor. FT-IR spectra of herbicide-clay
      or herbicide-humic acid-clay mixtures showed that H-bonding and charge transfer
      were the primary interaction pathways between these compounds and the surface of
      clay or humic acids. The different moieties attached to 2-chloro-acetanilide and
      their unique arrangement may have influenced the binding mechanisms and thus the
      sorptivity of these herbicides. This study indicates that the structural
      difference of pesticides in the same classes may be used as a molecular probe to
      obtain a better understanding of sorption mechanisms of pesticides on soil.

PMID- 11590718
TI  - Simultaneous nitrogen and phosphorus removal under low dissolved oxygen
      conditions.
AB  - A full-scale test was operated by using low dissolved oxygen activated sludge
      process to enhance biological nitrogen and phosphorus removal. When the influent
      concentrations of CODcr, TN and TP varied in a range of 352.9 mg/L-1338.2 mg/L,
      34.4 mg/L-96.3 mg/L, and 2.21 mg/L-24.0 mg/L, the average removal efficiencies
      were 94.9%, 86.7% and 93.0%, respectively. During the test period of two months,
      effluent means of CODcr, BOD5, NH3-N, TN and TP were below 50 mg/L, 25 mg/L, 10
      mg/L and 1.0 mg/L, respectively. The low dissolved oxygen activated sludge
      process has a simple flow sheet, fewer facilities and high N and P removal
      efficiency. It is very convenient to retrofit the conventional activated sludge
      process with the above process.

PMID- 11590719
TI  - Scale correlation between vegetation and soil in larch forest, NE China.
AB  - After the analysis on the linages of species, the fractal dimensions of
      vegetation and soil in a managed larch(Larix gmelini) forest in Daxingan
      Mountains, NE China were estimated separately, and their scale correlation was
      discussed. (1) The dominant species of the larch forest, larch and the important
      accompany species, birch(Betula platyphylla) were homogeneously distributed along
      the transect. The other species were heterogeneous, and can be divided into three
      groups located on the right, left and central parts of the transect respectively.
      The transect can be separated into two parts at the position for the 29th
      quadrat(580 m). (2) The fractal dimension in the large scale range from 200 to
      400 m was lower than that in the small scale range from 0 to 200 m in the forest,
      indicating the different variation regularities of spatial heterogeneity in
      different scale ranges. The inflection point at 200 m was one of the key scales
      of spatial hierarchy of the larch forest. (3) The scale variation of the forest
      was correlated with that of soil pH on large scales, which reflected the indirect
      control of the dominant species to the spatial pattern and species distribution
      of understorey by changing soil acidity in the forest and the indirect effects of
      forest management.

PMID- 11590720
TI  - Effect of long-term fertilization on soil nitrate distribution.
AB  - A thirteen years long-term field fertilizer experiment was conducted to monitor
      the effect of different fertilization on soil nitrate distribution. The results
      showed: (1) Applying relative excessive N fertilizer could result large
      quantities of NO3- residue and NO3- movement downward in soil profiles; amending
      phosphate fertilizer or organic manure with nitrogen fertilizer together could
      significantly improve the status of NO3- leaching downward due to the balanced
      uptake of nutrients by crops. (2) Appropriate amounts of nitrogen fertilizer
      which was equal or smaller than the optimal fertilization rate could not result
      in more NO3- leaching in Northern China. (3) Precipitation influenced the amounts
      and depth of soil NO3- leaching: NO3- could move to 80 cm depth or below at
      autumn or at the next spring when rainfall was higher during the rainy season
      through July to September in North China.

PMID- 11590721
TI  - TiO2-assisted photo-catalysis degradation process of dye chemicals.
AB  - The photo-catalytic degradation pathway and degradation products of methylene
      blue, rhodamine B, methyl orange, and malachite green in aqueous TiO2 suspension
      irradiated by high pressure mercury lamp by means of UV-visible absorption
      spectra and ion chromatography were investigated. The photo-catalysis degradation
      of dye solutions with charges was greatly effected by pH value owing to the
      electrostatic model. The photo-degradation rate of dyes anion increased with the
      decrease of pH value, in contrast, the photo-degradation rate of dyes cation
      increased with the increase of pH value. And the absorption peaks diminished with
      a blue shift. After illuminated for 30 minutes, a part of dye chemicals were
      completely mineralized and transferred into inorganic species including chloride
      ion, ammonium ion, nitrate ion, sulfate ion. And the addition of 100 mmol/L H2O2
      promoted the formation of inorganic species. In this study, the quantity of
      ammonium ion was much more than that of nitrate ion. That indicated the formation
      of nitrate is from ammonium. The purification rate of COD in four kinds of dye
      solution was 71.7%-88.7%. The decrease of COD of dyes solution implies the
      feasibility of the environmental application of photo-catalyzed process.

PMID- 11590722
TI  - Informational uncertainties of risk assessment about accidents of chemicals.
AB  - An analysis system of informational uncertainties for accidental risk assessment
      of chemicals is introduced. Statistical test methods and fuzzy sets method can do
      the quantitative analysis of the input parameters. The uncertainties of the model
      can be used by quantitative compared method for the leakage accidents of
      chemicals. The estimation of the leaking time is important for discussing
      accidental source term. The uncertain analyses of the release accident for
      pipeline gas (CO) liquid chlorine and liquid propane gas (LPG) have been
      discussed.

PMID- 11590723
TI  - Role of barium nitrate on the sulfur fixation of calcium oxide.
AB  - In this paper, the effect of Ba(NO3)2 on the efficiency of sulfur fixation of
      calcium oxide during coal combustion was studied. The results showed that
      addition of barium nitrate to the CaO can enhance the sulfur removal rate of CaO
      significantly. The X-ray diffraction spectrum of residual ash of coal added some
      sulfur fixative expressed that Ba2+ can form a compound of Ba-Al-Si-O which
      encloses the CaSO4 to prevent it's decomposition, so Ba2+ can improve the action
      of sulfur fixation of CaO. The combustion character of the original coal and
      original coal added sulfur fixative was researched with thermal-gravity analyzer
      and the results expressed that adding some sulfur fixative to the coal will make
      the combustion character of coal change little.

PMID- 11590724
TI  - A tool model for predicting atmospheric chemical kinetics with sensitivity
      analysis.
AB  - A package(a tool model) for program of predicting atmospheric chemical kinetics
      with sensitivity analysis is presented. The new direct method of calculating the
      first order sensitivity coefficients using sparse matrix technology to chemical
      kinetics is included in the tool model, it is only necessary to triangularize the
      matrix related to the Jacobian matrix of the model equation. The Gear type
      procedure is used to integrate a model equation and its coupled auxiliary
      sensitivity coefficient equations. The FORTRAN subroutines of the model equation,
      the sensitivity coefficient equations, and their Jacobian analytical expressions
      are generated automatically from a chemical mechanism. The kinetic representation
      for the model equation and its sensitivity coefficient equations, and their
      Jacobian matrix is presented. Various FORTRAN subroutines in packages, such as
      SLODE, modified MA28, Gear package, with which the program runs in conjunction
      are recommended. The photo-oxidation of dimethyl disulfide is used for
      illustration.

PMID- 11590725
TI  - Survey of polycyclic aromatic hydrocarbons (PAHs) in arterial street air of
      Hangzhou.
AB  - The presence of particulate and vapor PAHs, SO2 and NOx and other interrelated
      conditions (temperature, traffic intensity and wind velocity) were investigated
      in the arterial street air of Hangzhou. The concentration of the nine PAHs in the
      air was mean to 11.7 micrograms/m3, and the content of benzo(a) pyrene was up to
      0.108 microgram/m3. The contents of PAHs in the sampling sites were in good
      relation to the traffic intensity, and would be also affected by the terrain and
      meteorological conditions. The occurrences of PAHs in ambient air were mainly
      affected by their physical, chemical characters and temperature. The three- and
      four-ring PAHs (MW < or = 228) mainly existed in the vapor phase and the five
      ring PAHs (MW > 228) existed predominately in the particulate phase. The fraction
      of vapor PAHs in the total nine PAHs was 84.2% in the air of the sampling sites.
      In the morning and evening, the concentrations of PAHs in the arterial street air
      were higher than that on the noon and the diurnal variation of PAHs was similar
      to that of the traffic gas NOx. A conclusion would be drawn that the major source
      of PAHs in the arterial street air was the traffic. And the results indicated
      that 75% of BaP would come from traffic source and remaining 25% of BaP would
      come from non-traffic source.

PMID- 11590726
TI  - Analysis of ingredient and heating value of municipal solid waste.
AB  - Great differences between municipal solid wastes (MSW) produced at different
      places and different times in terms of such parameters as physical ingredient and
      heating value lead to difficulty in effective handling of MSW. In this paper,
      ingredient, heating value and their temporal varying trends of typical MSW in
      Beijing were continuously measured and analyzed. With consideration of the
      process in pyrolysis and incineration, correlation between physical ingredients
      and heating values was induced, favorable for evaluation of heating value needed
      in handling of MSW from simple analysis of physical ingredients of it.

PMID- 11590727
TI  - Bioamendment of petroleum contaminated ultisol: effect on oil content, heavy
      metals and pH of tropical soil.
AB  - The effect of organic amendments on the oil content, heavy metals concentration
      and pH of petroleum contaminated sandy loam ultisol obtained from Rumuekpe oil
      field in Emohua Local Government Area of Rivers State, Nigeria was determined.
      Petroleum contaminated soils were treated with wood ash, compost and sawdust. The
      addition of organic amendments resulted in a significant (at 95% probability
      level) decrease in oil content by 92% for composting, 81% for soil treated with
      sawdust and 58% for soil with ash supplementation, over 6 months. The effect of
      treatments on the iron(Fe), copper(Cu) and lead(Pb) concentration was significant
      at P < 0.001. The remediation also affected the pH of soil. This initial pH of
      5.6 was depressed by the application of compost and sawdust supplements
      respectively to a final pH of 5.2 and 5.3. On the other hand, amending the soil
      with wood ash raised the pH from 5.6 to 6.2. Increased acidity caused a decrease
      in the heavy metals concentration in the contaminated soil. Soil treatment with
      compost generally gave the best remediation results, followed by sawdust and then
      ash. Adjusting the pH of oil contaminated soil to high acidic levels may promote
      the availability and migration of heavy metals in remediated soils and not
      necessarily the rate of oil mineralization.

PMID- 11590728
TI  - Hydrolysis kinetics of atrazine and influence factors.
AB  - The hydrolysis kinetics of atrazine in distilled water and leaching water from
      soil, and their influence factors were studied by incubation at 35 degrees C and
      HPLC analysis method. The kinetic process of atrazine hydrolysis can be described
      by the first-order reaction law. The results showed that the hydrolysis rate
      constants k in leaching water and distilled water were 1.606 x 10(-3)/d and 1.055
      x 10(-3)/d, respectively; the half-life of atrazine hydrolysis in distilled water
      at pH 3, pH 4.5 and pH 8 were 373 days, 522 days and 657 days respectively. The
      results also showed that the proton in reaction solution can catalyze the
      atrazine hydrolysis; humic acid and NH4+ etc. substances in aqueous solution can
      facilitate atrazine hydrolysis; rate constants of atrazine hydrolysis with humic
      acid and NH4NO3 were 2.431 x 10(-3)/d and 1.498 x 10(-3)/d respectively which
      were 2.3 and 1.42 times of control (1.055 x 10(-3)/d); anion NO3- can inhibit
      catalysis of humic acid to atrazine hydrolysis.

PMID- 11590729
TI  - Partition of polycyclic aromatic hydrocarbons on organobentonites from water.
AB  - A series of organobentonites synthesized by exchanging organic cation such as
      dodecyltri-methylammonium (DTMA), benzyldimethyltetradecylammonium (BDTDA),
      cetyltrimethyl-ammonium (CTMA), octodeyltrimethylammonium (OTMA) on bentonite.
      The optimal condition, properties and mechanisms for the organobentonites to sorb
      phenanthrene, anthracene, naphthalene, acenaphthene in water were investigated in
      detail. The partition behavior was determined for four polycyclic aromatic
      hydrocarbons (PAHs), such as naphthalene, phenanthrene, anthracene and
      acenaphthene, from water to a series of organobentonites. The interlayer spacings
      and organic carbon contents of organobentonites, removal rate and sorption
      capacities for organobentonites to treat phenanthrene, anthracene, naphthalene,
      acenaphthene were correlated to the length of alkyl chains and the amounts of
      cation surfactant exchanged on the bentonite. Phenanthrene, anthracene,
      naphthalene, and acenaphthene sorption to organobentonites were characterized by
      linear isotherms, indicating solute partition between water and the organic phase
      composed of the large alkyl functional groups of quaternary ammonium cations.
      PAHs distribution coefficients (Kd) between organobentonites and water were
      proportional to the organic carbon contents of organobentonites. However, the
      partition coefficients (Koc) were nearly constants for PAHs in the system of
      organobentonite-water. The Koc of phenanthrene, anthracene, naphthalene,
      acenaphthene were 2.621 x 10(5), 2.106 x 10(5), 2.247 x 10(4), 5.085 x 10(4),
      respectively. The means Koc values on the organobentonites are about ten to
      twenty times larger than the values on the soils/sediments, what is significant
      prerequisite for organobentonite to apply to remediation of pollution soil and
      groundwater. The sorption mechanism was also evaluated from octanol-water
      partition coefficients and aqueous solubility of PAHs. The correlations between
      1gKoc and 1gKow, 1gKoc and 1gS for PAHs in the system of water/organobenotonites
      are also discussed.

PMID- 11590730
TI  - Adsorption of acetanilide herbicides on soil and its components. II. Adsorption
      and catalytic hydrolysis of diethatyl-ethyl on saturated Na(+)-, K(+)-, Ca(2+)-,
      and Mg(2+)-montmorillonite.
AB  - Adsorption and catalytic hydrolysis of the herbicide diethatyl-ethyl [N
      chloroacetyl-N-(2,6-diethylphenyl)glycine ethyl ester] on homoionic Na(+)-, K(+)
      , Ca(2+)-, and Mg(2+)-montmorillonite clays were investigated in water solution.
      The Freundlich adsorption coefficient, Ki, got from isotherms on clay followed
      the order of Na+ approximately K+ > Mg2+ approximately Ca2+. Analysis of FT-IR
      spectra of diethatyl-ethyl adsorbed on clay suggests probable bonding at the
      carboxyl and amide carbonyl groups of the herbicide. The rate of herbicide
      hydrolysis in homoionic clay suspensions followed the same order as that for
      adsorption, indicating that adsorption may have preceded and thus caused
      hydrolysis. Preliminary product identification showed that hydrolysis occurred
      via nucleophilic substitution at the carboxyl carbon, causing the cleavage of the
      ester bond and formation of diethatyl and its dechlorinated derivative, and at
      the amide carbon, yielding an ethyl ester derivative and its acid. These pathways
      also suggest that hydrolysis of diethatyl-ethyl was catalyzed by adsorption on
      the clay surface.

PMID- 11590731
TI  - Protozoan colonization on artificial substrates in relation to water quality in a
      tropical Indian harbour.
AB  - A field study was conducted to evaluate the protozoan colonization patterns on
      artificial substrates in relation to organic pollution within a tropical harbour.
      The composition of protozoans and their succession rates on artificial
      substrates(polyurethane foam units) were compared between two field stations(A
      and B), and their presence were considered with regards to the prevailing water
      quality conditions at the study sites. Altogether 44 genera of flagellates and
      ciliates were documented. The common genera of flagellates encountered included
      Monas, Polytoma, and Chromalina. Among the ciliates, the predominant genera were
      Tetrahymena, Vorticella, Lagymophyra, and Heloiphyra. These groups exhibited
      characteristic successional patterns in relation to ambient water quality. At
      Station A, located close to the sewage outfall, the water quality parameters
      included poor Secchi-disc transparency(0.48 m), dissolved oxygen of 1.93 mg/ml,
      salinity of 18 psu, and temperature 31.3 degrees C. Here, the nanoflagellates
      (spumella) colonized first, followed by microcilliate(Tetrahymena) and sessile
      form(Vorticella). Station B, located on the seaward side, was characterized by
      relatively less-stressed environmental conditions with transparency 1.85 m and
      dissolved oxygen value of 6.04 mg/ml. Salinity of 27.27 psu, and mean temperature
      of 30 degrees C were recorded at "B". At this station, the nanoflagellate
      Polytoma was first documented to colonize on the substrates, followed by
      microcilliate(Lagynophrya) and suctorid(Heliophyra). These findings support the
      use of protozoans as indicator species for evaluating the hazards posed by
      organic pollution to natural estuarine communities.

PMID- 11590732
TI  - Distribution of atrazine in a crop-soil-groundwater system at Baiyangdian Lake
      area in China.
AB  - In this paper, the concentration distribution and environmental fate of atrazine
      in a crop-soil-groundwater system at Baiyangdian Lake area of North China were
      studied. The concentration of the herbicide in spatial and vertical soils, and in
      roots, stem, leaf, corncob and kernel of corn, and in groundwater were measured
      by HPLC. The results showed that the variation of spatial concentration of
      atrazine in soil can be described by first-order kinetics equation which has a
      half-life of 360 days and a rate constant of 0.0019 d-1. The vertical variation
      of atrazine concentration with soil depth follows the exponential decay law.
      After 120 days following atrazine application, the mass distributions of this
      herbicide in crop-soil-groundwater system are 71% in soil, 20% in groundwater and
      1% in crop respectively, and 8% due to loss by degradation or often removal
      processes. The order of atrazine concentration in every part of corn crop is in
      roots > in corncob > in kernel of corn > in leaf.

PMID- 11590733
TI  - Interaction of Cd and citric acid, EDTA in red soil.
AB  - Adsorption and desorption process of cadmium in red soil (Ferrisols) as well as
      the influence by media's pH were investigated in detail with and without citric
      acid and EDTA. Experimental results clearly showed that Cd adsorption in red soil
      was affected significantly by the coexisted organic chemicals. In the presence of
      citric acid and EDTA, Cd adsorption in red soil increased with pH in acid media
      but decreased in high pH one. Further studies placed stress on the adsorbed Cd in
      red soil which was found to be existed mainly as exchangeable one at pH < 5.5,
      and desorption rate by 0.10 mol/L NaNO3 gave a peak-shaped curve due to the
      difference of specifically and nonspecifically adsorbed Cd with pH's change.

PMID- 11590734
TI  - Membrane bioreactor process of organic wastewater from brassylic acid
      manufacturing plant.
AB  - The wastewater treatment from brassylic acid manufacturing plant using membrane
      bioreactor (MBR) was studied. The membrane bioreactor consisted of batch
      operation biological aeration tank and ultrafiltration evaluation tank. The
      content of test included the affection of variation operation conditions on
      ultrafiltration separation, the general characteristics of MBR process, and the
      difference comparing with the conventional biological treatment. The results are
      as follows: (1) among the test membrane material, polyether sulphone (PES)
      membrane is more suitable for the wastewater treatment; (2) when the cutoff
      molecular weight is among 10,000-50,000, the higher the cutoff molecular weight,
      the bigger the water flux is in the test; (3) under the operation pressure, water
      flux increases accompanying with the increasing of operation pressure; (4) the
      paper filtered COD concentration has more affection on the water flux than the
      suspended solid concentration; (5) as the volume loading of MBR increases, the
      accumulation of high molecule organic substance and colloid increases, the
      membrane permeate COD concentration and paper filtered COD concentration increase
      too, meanwhile the water flux reduces; (6) when the sludge retention time of
      activated sludge of MBR increases, the accumulation of high molecule organic
      substance and colloid reduces, the membrane permeate COD concentration and paper
      filtered COD concentration reduce too, and the water flux increases; (7)
      comparing with the conventional biological process, the microbial activity is
      higher, but the microbial species is less.

PMID- 11590735
TI  - Phenotypic nutrient up-take differences in an alley cropping system in semi-arid
      Machakos, Kenya.
AB  - Alley cropping of Cassia siamea and maize was studied in semi-arid Kenya for soil
      fertility improvement. Katumani composite maize was planted except in the short
      rains of 1988 (SR88) when a hybrid variety was sown. Therefore the grain yield
      per row increased differently in the alley cropped maize (CM). Sole maize (SM)
      and CM yields were higher in SR88 than in the long rains of 1988 (LR88) by 62%
      and 38%, while yields from the same treatments in LR89 were only 21% and 45% of
      those in SR88. These differences in relative maize yields are attributed to
      differences between the two maize varieties in competition under nutrient stress
      conditions.

PMID- 11590736
TI  - Fractal scaling of effective diffusion coefficient of solute in porous media.
AB  - Fractal approach is used to derive a power law relation between effective
      diffusion coefficient of solute in porous media and the geometry parameter
      characterizing the media. The results are consistent with the empirical equations
      analogous to Archie's law and are expected to be applied to prediction of
      effective diffusion coefficient.

PMID- 11590737
TI  - Exploiting pattern and sustainable development of marginal lands in the Three
      Gorge Reservoir Areas.
AB  - This paper studied the distribution and utilization status, reasonable
      exploitation patterns and potential productivity, and sustainable development of
      marginal lands in the Three Gorge Reservoir Areas. It has been pointed that
      problems of the soil fertility degradation, poor productivity in crop lands,
      natural disasters and environmental deterioration existed in all the exploited
      marginal lands. In order to maintain the sustainability of the marginal lands,
      following measure have been proposed: prohibiting cultivation in the crop lands
      with a slope more than 25 degrees, restoring vegetation in the slope more than 25
      degrees, strengthening the basic agricultural construction, establishing the
      production base of woody feeds and oils, establishing a multi-dimensional
      management model with reasonable structure and optimum function for forestry,
      agriculture and fishing.

PMID- 11590738
TI  - Environmental impact of radionuclide migration in groundwater from a low
      intermediate level radioactive waste repository.
AB  - The radionuclide migration from a certain Chinese repository with low
      intermediate level radioactive solid waste is studied. The migration in
      groundwater is analyzed and computed in detail. Under presumption of normal
      releasing, or the bottom of the repository has been marinated for one month with
      precipitation reaching 600 mm once and a 6 m aerated zone exists, a prediction
      for 7 radionuclides is conducted. It shows that the aerated zone is the primary
      barrier for migration. The migration for radionuclides 60Co, 137Cs, 90Sr, 63Ni,
      etc. will be retarded in it within 500 years. The concentration of 239Pu will be
      decreased by amount of 6 order. Only 3H and 14C can migrate through the aerated
      zone. The radionuclides that go through the aerated zone and enter the aquifer
      will exist in spring, stream and sea. Based on this, the intake dose by residents
      in different age group resulting from drinking contaminated spring water, eating
      seafood is calculated. The results showed that the impact of the repository to
      the key resident group is lower than the limit in national repository regulation
      standard. This complies with the repository management target.

PMID- 11590739
TI  - Internal circulating fluidized bed incineration system and design algorithm.
AB  - The internal circulating fluidized bed (ICFB) system is characterized with fast
      combustion, low emission, uniformity of bed temperature and controllability of
      combustion process. It is a kind of novel clean combustion system, especially for
      the low-grade fuels, such as municipal solid waste (MSW). The experimental
      systems of ICFB with and without combustion were designed and set up in this
      paper. A series of experiments were carried out for further understanding
      combustion process and characteristics of several design parameters for MSW.
      Based on the results, a design routine for the ICFB system was suggested for the
      calculation of energy balance, airflow rate, heat transfer rate, and geometry
      arrangement. A test system with ICFB combustor has been set up and the test
      results show that the design of the ICFB system is successful.

PMID- 11590740
TI  - Improving the numerical stability of the MAGIC model.
AB  - MAGIC is one of the most widely used models for forecasting long-term
      acidification. The model's code, however, has been experiencing numerical
      instability, though this might not be widely known to the public users. The major
      instability comes from the analytical solution to two cubic equations for
      calculating SO4(2-) concentration and the exchangeable fraction of Al on the
      soils. The mathematical algorithm for calculating the concentration of SO4(2-)
      from a quadratic equation is also found unstable. This paper is aimed at
      improving the instability above through proved numerical algorithms.

PMID- 11590741
TI  - Agricultural adaptation of climate change in China.
AB  - This paper presents the study on agriculture adaptation to climate change by
      adopting the assumed land use change strategy to resist the water shortage and to
      build the capacity to adapt the expected climate change in the northern China.
      The cost-benefit analysis result shows that assumed land use change from high
      water consuming rice cultivation to other crops is very effective. Over 7
      billions m3 of water can be saved. Potential conflicts between different social
      interest groups, different regions, demand and supply, and present and future
      interests have been analyzed for to form a policy to implement the adaptation
      strategy. Trade, usually taken as one of adaptation strategies, was suggested as
      a policy option for to support land use change, which not only meets the
      consumption demand, but also, in terms of resources, imports water resources.

PMID- 11590742
TI  - A new technology for harnessing the dye polluted water and dye collection in a
      chemical factory.
AB  - A new technology for harnessing the dye polluted water and dye collection was
      developed. It is based on the enhanced evaporation by using solar, wind and air
      temperature energy and additional heat-electric energy. It consists of four
      parts: (1) evaporation carrier system (evaporation carrier and frame for
      evaporation carrier) for polluted water; (2) polluted water circulating system
      (pumping-spraying-collecting); (3) heating system; (4) workshop with polluted
      water reservoir-tanks and rainfall prevention roof. The polluted water was
      (heated in case necessary) sprayed to the evaporation carrier system and the
      water was evaporated when it moved in the space and downward along the carrier
      mainly by using natural (solar, wind and air temperature energy). In case, when
      there is no roof for the carrier system, the polluted water can be stored in the
      reservoirs (storage volume for about 20 days). The first 10-25 mm rainfall also
      need to be stored in the reservoirs to meet the state standard for discharging
      wastewater. The dye may be collected at the surface in the reservoir-tanks and
      the crystallized salt may be collected at the bottom plate. The black-color
      wastewater released by the factory is no more discharged to the surface water
      system of Taihu Lake Basin. About 2 kg dye and 200 kg industrial salt may be
      collected from each tone of the polluted water. The non-pollution production of
      dye may be realized by using this technology with environmental, economical and
      social benefits.

PMID- 11590743
TI  - Enhanced photo--catalytic activity of gold ion and gold modified.
AB  - The gold ion modified TiO2 was prepared by means of sol-gel whereas gold
      deposited TiO2 was prepared by means of photo-reduction. The physical properties
      were influenced significantly by the presence of gold ion or gold. The enhanced
      photo-activity of gold modified TiO2 was quantified in terms of methylene blue
      degradation. The presence of gold ion in TiO2 lattices or gold on TiO2 surface
      enhanced their photo-activity. The optimum molar content of gold ion doping and
      gold deposition all was 0.5%. The first-order rates constants of gold modified
      TiO2 was more than that of pure TiO2, and decreased by increasing the content of
      gold ion and gold when their contents were more than 0.5%. Gold ion doped in TiO2
      lattices was more effective to enhance the photo-activity than gold on TiO2
      surface. Moreover, the relationship between physical properties, chemical
      properties and photo-activity has been discussed.

PMID- 11590744
TI  - Chinese life cycle impact assessment factors.
AB  - The methodological basis and procedures for determination of Chinese
      normalization references and weighting factors according to the EDIP-method is
      described. According to Chinese industrial development intensity and population
      density, China was divided into three regions and the normalization references
      for each region were calculated on the basis of an inventory of all of the
      region's environmental emissions in 1990. The normalization reference was
      determined as the total environmental impact potential for the area in question
      in 1990 (EP(j)90) divided by the population. The weighting factor was determined
      as the normalization reference (ER(j)90) divided by society's target contribution
      in the year 2000 based on Chinese political reduction plans, ER(j)T2000. This
      paper presents and discuss results obtained for eight different environmental
      impact categories relevant for China: global warming, stratospheric ozone
      depletion, acidification, nutrient enrichment, photochemical ozone formation and
      generation of bulk waste, hazardous waste and slag and ashes.

PMID- 11590745
TI  - Heavy metal concentrations in edible bivalves and gastropods available in major
      markets of the Pearl River Delta.
AB  - Molluscs are able to accumulate heavy metals and impose health hazard to
      consumers. The main objective of the present study is to investigate the heavy
      metal concentrations in edible bivalves and gastropods available in major markets
      of the Pearl River Delta. Fourteen species of edible molluscs were purchased from
      six markets in Hong Kong and Guangdong Province. The fresh of these biota were
      tested for their cadmium (Cd), copper (Cu), zinc (Zn), lead (Pb), nickel (Ni),
      chromium (Cr), antimony (Sb) and tin (Sn) concentrations (based on wet weight).
      The results indicated that amongst the 14 edible molluscs, only Cd, Pb, Ni, Cr,
      Sb and Sn concentrations in three species (Ruditapes philippinarum, Perna viridis
      and Hemifusus tuba) were within the local regulatory limits. Over 60% of bivalve
      species exceeded maximum permitted levels of Cd (2 micrograms/g) and Cr (1
      microgram/g), while over 40% of gastropod species exceeded the maximum levels of
      Sb (1 microgram/g) and Cr (1 microgram/g). Most of the samples collected from
      Hong Kong had significantly higher contents of Pb and Sb, but similar levels of
      Cd, Cu and Zn when compared with samples collected across the border (p < 0.05; p
      < 0.01; p < 0.001 respectively). In general, the molluscs purchased in Guangdong
      markets had higher metal contents than those purchased from the Hong Kong
      markets. When compared with the Provisional Tolerable Weekly Intake or Maximum
      Acceptable Daily Load recommended by FAO/WHO Expert Committee on Food Additives,
      Cd levels of five species (Anadara ferruginea, Pinna pectinata, Chlamys nobilis,
      Babylonia lutosa and Hemifusus terntanus) and Cr levels of seven species (Anadara
      ferruginea, Paphia undulata, Pinna pectinata, Babylonia lutosa, Hemifusus
      terntanus, Cymbium melo and Cipangopaludina chinensis) were higher than both the
      human daily acceptable limits (for Cd and Cr respectively) and the local
      regulatory levels (for Cd and Cr respectively).

PMID- 11590746
TI  - Pollution of water resources due to industrialization in arid zone of Rajasthan,
      India.
AB  - In arid zone of Rajasthan, India, nearly 21,900 hm2 area along Bandi River has
      been affected by industrial effluent discharge into the river bed. Analysis of
      groundwater samples collected from these sites revealed that area at the vicinity
      of the river is most affected. The effluent water in the river is the main source
      of contamination of ground water. Concentration of sodium and chloride has been
      higher with proportional increase in TDS and EC value in the area within zone A
      (river water), zone B (0-100 m), zone C (101-250 m), zone D (251-500 m) and zone
      E (501-1000 m). There is decreasing trend in ion concentration from zone A to
      zone E and F, reflecting reduced effect of effluents. The pollution of water
      resources has resulted in the degradation of other natural resources such as
      land, soil and vegetation. Nearly 4463 hm2 (20.38%) area has been very severely
      affected. EC value at places exceeds 20 dS/m. Soil and land have become hard,
      compact and saline. Cropping intensity has declined. In the area (3633 hm2)
      affected severely, the EC value of water varies from 10-20 dS/m. Irrigation with
      such water has created problem of salinity, sodicity in soils. Herbal biomass
      declined considerably. Double cropping has almost stopped. Almost 8494 hm2 area
      is affected moderately. EC of ground water varies from 5 to 10 dS/m. Fragile
      surface crust, declining trend of phosphorous and potassium in the soil, poor
      density of natural vegetation are significant manifestations. Apart from this,
      5305 hm2 area is slightly affected.

PMID- 11590747
TI  - Environmental change in Bashang region historical periods.
AB  - The Bashang region is a typical vulnerable eco-environmental zone. Our analysis
      of paleodunes, paleosol profiles, and lake changes taking place during last ten
      thousands years indicated that: (1) 10-6.9 ka B.P. was a post-glacial temperature
      increasing stage, in which lakes had their high water level; (2) 6.9-3.0 ka B. P.
      was a large warm stage, during which four paleosol layers were developed and
      climate fluctuation has assumed 4-5 small cold-humid and cold-dry alternations.
      Since 5.4 ka B.P., the lakes tended to gradually shrink; and by 2.1 ka B.P.,
      water level has fallen by 2.7 m; (3) since 3.0 ka B. P. a general trend of the
      region was to change into a dry, warm-dry and cold-dry environment.

PMID- 11590748
TI  - Uptake and accumulation of copper by roots and shoots of maize (Zea mays L.).
AB  - The effects of different concentrations of copper sulfate on root and shoot
      growth of maize(Zea mays L.) and the uptake and accumulation of Cu2+ by its roots
      and shoots were investigated in the present study. The concentrations of copper
      sulfate (CuSO4 x 5H2O) used were in the range of 10(-5)-10(-3) mol/L. Root growth
      decreased progressively with increasing concentration of Cu2+ in solution. The
      seedlings exposed to 10(-3) mol/L Cu2+ exhibited substantial growth reduction,
      yielding only 68% of the root length of the control. The shoot growth of the
      seedlings grown at 10(-5)-10(-4) mol/L Cu2+ were more or less the same as the
      control seedlings. The leaves treated with 10(-3) mol/L Cu2+ were obviously
      inhibited in shoot growth. The fresh and dry weights both in roots and shots
      decreased progressively with increasing Cu2+ concentration. This fits well with
      the above mentioned effects of copper sulfate on root growth. Zea mays has
      considerable ability to remove Cu from solutions and accumulate it. The Cu
      content in roots of Z. mays increased with increasing solution concentration of
      Cu2+. The amount of Cu in roots of plants treated with 10(-3), 10(-4) and 10(-5)
      mol/L Cu2+ were 10, 8 and 1.5 fold, respectively, greater than that of roots of
      control plant. However, the plants transported and concentrated only a small
      amount of Cu in their shoots.

PMID- 11590749
TI  - Impacts of ozone on the biomass and yield of rice in open-top chambers.
AB  - The impacts of different O3 concentration on the biomass and yield of rice were
      studied by using OTC-1 open-top chambers. Experimental treatments included the
      activated charcoal-filtered air (CFA), 50 nl/L (CF50), 100 nl/L (CF100) and 200
      nl/L (CF200) concentrations of O3. The O3 treatments significantly decreased the
      total biomass per plant. The elevated O3 exposure resulted in a more decrease in
      the root growth than in the shoot growth. Assessments of yield characteristics at
      the final harvest revealed an O3-induced decrease in the number of grains per
      plant, resulting from fewer ears per plant, fewer grains per ear and more
      unfilled grains per ear. The 1000 grain dry weight and the harvest index (HI)
      were not changed significantly under 50 nl/L or 100 nl/L O3 exposure, but reduced
      by 17.0% and 4.8% by 200 nl/L O3 treatment, respectively. Compared to the CFA
      treatment, CF50, CF100 and CF200 treatments caused a 8.2%, 26.1%, 49.1% decrease
      of the grain yield per plant, and a 14.2%, 31.7%, 51.7% decrease of the total
      biomass per plant, respectively. Linear regression showed that the 7 h-daily mean
      O3 concentration exposure for 3 months (July-September) and AOT40 (cumulative
      exposure accumulation over threshold 40 nl/L) were well correlated with the
      relative grain yield. A yield loss of 10% was estimated to be at 46.9 nl/L O3 for
      7 h-daily mean O3 concentration exposure or at 12930 nl/(L.h) O3 for AOT40.

PMID- 11590750
TI  - Effect and mechanism of coking residual ammonia water treating by flue gas.
AB  - The treatment of coking residual ammonia water has been a big difficult problem
      at home and abroad, and there is no breakthrough research achievement in the
      past. The invention patent "The method of treating all coking wastewater or
      treating coking residual ammonia water by flue gas" has been successfully used in
      Huaian Steel Works for high concentration and organic industry wastewater
      treatment. Not only can it realize the wastewater zero discharge, but also the
      wastewater treatment has an effect of de-sulfur and de-nitrogen for flue gas. So
      that the flue gas exhaust can meet the requirement of emission standard. The mass
      transfer and heat transfer, fly ash absorption and coagulation, acid and alkali
      neutralization reaction, catalysis oxidation and reduction reaction in flue gas
      would be the major factors.

PMID- 11590751
TI  - Spatial distribution analysis on climatic variables in northeast China.
AB  - Information ecology is a new research area of modern ecology. Here describes the
      spatial distribution analysis methods of four sorts of climatic variables, i.e.
      temperature, precipitation, relative humidity and sunshine fraction in Northeast
      China. First, digital terrain models was built with large-scale maps and vector
      data. Then trend surface analysis and interpolation method were used to analyze
      the spatial distribution of these four kinds of climatic variables at three
      temporal scale: (1) monthly data; (2) mean monthly data of thirty years, and (3)
      mean annual data of thirty years. Ecological information system were used for
      graphics analysis on the spatial distribution of these climatic variables.

PMID- 11590752
TI  - Oil spill model development and application for emergency response system.
AB  - The paper introduces systematically the developing principle of CWCM 1.0 oil
      spill model based on Lagrange system and oil spill fate processes in environment,
      reviews two oil spill incidents of "East Ambassador" in Jiaozhou Bay and "Min
      Fuel 2" in the mouth of Pearl River, and designs the predictable system
      simulating oil spill applied in contingency plans. It is indicated that CWCM 1.0
      has met preliminarily the demands for functions of precision simulating and
      predicting oil spill, and can plan an important role to support oil spill
      response.

PMID- 11590753
TI  - Engineering for problem solving in future: eco-social market economy and eco
      social tech.
AB  - The paper differentiates approaches in technology (end-of-pipe, cleaner
      production, industrial ecology, zero emission and eco-social-tech) and compares
      them in respect to the problem solving capacity on the ecological as well as
      social dimension by showing the eco-impact reduction and job creation. Eco-social
      tech represents the approach with highest problem solution as it is based on "eco
      social market economy", which will the replace free market economy. The deep
      background of these innovations is "ecosophy", the wisdom of nature, which serves
      as guideline for eco-restructuring the world.

PMID- 11590754
TI  - Influence of fuel quality on vehicular NOx emissions.
AB  - The quality of gasoline and diesel fuel affects pollutant emissions from
      vehicles. By applying the COMPLEX model, developed by the US EPA and industry to
      relate fuel composition to vehicle emissions, this paper estimates the influence
      of improvements in gasoline quality to lower vehicular NOx emissions. A case
      study is performed for Guangzhou City that has NOx concentrations significantly
      above the national ambient air quality standards(NAAQS). The paper discusses the
      potential for reducing NOx in Guangzhou by improving the quality of gasoline.

PMID- 11590755
TI  - Chromium-induced membrane damage: protective role of ascorbic acid.
AB  - Importance of chromium as environmental toxicant is largely due to impact on the
      body to produce cellular toxicity. The impact of chromium and their
      supplementation with ascorbic acid was studied on plasma membrane of liver and
      kidney in male Wistar rats (80-100 g body weight). It has been observed that the
      intoxication with chromium (i.p.) at the dose of 0.8 mg/100 g body weight per day
      for a period of 28 days causes significant increase in the level of cholesterol
      and decrease in the level of phospholipid of both liver and kidney. The alkaline
      phosphatase, total ATPase and Na(+)-K(+)-ATPase activities were significantly
      decreased in both liver and kidney after chromium treatment, except total ATPase
      activity of kidney. It is suggested that chromium exposure at the present dose
      and duration induce for the alterations of structure and function of both liver
      and kidney plasma membrane. Ascorbic acid (i.p. at the dose of 0.5 mg/100 g body
      weight per day for period of 28 days) supplementation can reduce these structural
      changes in the plasma membrane of liver and kidney. But the functional changes
      can not be completely replenished by the ascorbic acid supplementation in
      response to chromium exposure. So it is also suggested that ascorbic acid
      (nutritional antioxidant) is useful free radical scavenger to restrain the
      chromium-induced membrane damage.

PMID- 11590756
TI  - Bipolar charged aerosol agglomeration and collection by a two-zone agglomerator.
AB  - In older to collect fine particles more efficiently, a new-type electrostatic
      agglomerator with two zones was developed. The distinguishing feature of this
      electrostatic agglomerator is that the particles are bipolarly charged and
      coagulated in the same alternating electric field simultaneously. The silica
      flour with 2 microns mass median diameter and the smoke from burning wood powder
      were used as test aerosol. The comparison experimental results have shown that
      when the mean electric field is 4 kV/cm the collection efficiency of the new
      electrostatic agglomerator was 98.2% for silica flour and 67.4% for wood powder
      smoke. Under the same experimental condition, the collection efficiency of the
      electrostatic agglomerator with three zones was 97.4% for collecting silica flour
      and the collection efficiency of the electrostatic precipitator was 56.3% for
      wood powder smoke.

PMID- 11590757
TI  - Model calculating annual mean atmospheric dispersion factor for coastal site of
      nuclear power plant.
AB  - This paper describes an atmospheric dispersion field experiment performed on the
      coastal site of nuclear power plant in the east part of China during 1995 to
      1996. The three-dimension joint frequency are obtained by hourly observation of
      wind and temperature on a 100 m high tower; the frequency of the "event day of
      land and sea breezes" are given by observation of surface wind and land and sea
      breezes; the diffusion parameters are got from measurements of turbulent and wind
      tunnel simulation test. A new model calculating the annual mean atmospheric
      dispersion factor for coastal site of nuclear power plant is developed and
      established. This model considers not only the effect from mixing release and
      mixed layer but also the effect from the internal boundary layer and variation of
      diffusion parameters due to the distance from coast. The comparison between
      results obtained by the new model and current model shows that the ratio of
      annual mean atmospheric dispersion factor gained by the new model and the current
      one is about 2.0.

PMID- 11590758
TI  - Understanding yields in alley cropping maize (Zea mays L.) and Cassia siamea Lam.
      under semi-arid conditions in Machakos, eastern Kenya.
AB  - Six seasons of experiments in Machakos, Kenya, revealed that above about 150 mm
      of rainfall, maize yields per row in alley cropped "replacement" agroforestry
      (AF) plots, of Cassia siamea Lam. and maize (Zea mays, cv. Katumani Composite B),
      may be expected to exceed those in the control (sole maize) plots. Such yields
      were insufficient to compensate for the area "lost" to the hedgerows. Below about
      150 mm the control plots may be expected to perform better. This result was due
      to competition for water. Greater association of the fine roots of Cassia and
      maize was observed in the middle of the alleys than near the hedgerows.
      Photosynthetic consequences of shading were insignificant relative to other
      factors. In the alleys, reductions of soil temperature due to shade in the
      western and eastern maize rows were higher than in the middle row. Soil moisture
      extraction was higher in the AF than in the control plots. In the AF plots,
      moisture extraction was greater under the central maize rows than under those
      nearest the Cassia. Yield patterns followed such soil temperature and soil
      moisture patterns. Maize transpiration and photosynthetic rates were
      significantly higher in the control than in the AF plots during a below-average
      rainy season but not during above-average rainy seasons. It is concluded that
      alley cropping under semi-arid conditions should be approached differently from
      the system worked on. It must at least provide strong physical protection of
      crops and/or soils and have a strong economic incentive to be of interest to the
      farmers.

PMID- 11590759
TI  - Predicting octanol/water partition coefficient using solvation free energy and
      solvent-accessible surface area.
AB  - The regression model for octanol/water partition coefficients (Kow), is founded
      with only two molecular descriptors available through quantum chemical
      calculations: solvation free energy (delta Gs), and solvent-accessible surface
      area (SASA). For the properties of 47 organic compounds from 17 types, the model
      gives a correction coefficient (adjusted for degrees of freedom) of 0.959 and a
      standard error of 0.277 log unit. It is a suitable way to predict the partition
      properties that are related to solute-solvent interactions in the water phase.

PMID- 11590760
TI  - Comparison of degradation reactions of Acid Yellow 61 in both oxidation processes
      of H2O2/UV and O3.
AB  - The comparison of degradation of Acid Yellow 61 as a model dye compound in both
      oxidation processes of H2O2/UV and O3 has been studied. When the decolorization
      rate of Acid Yellow 61 in both reactions presented similar, it was found there
      are some differences from the results of AOX removal and production of inorganic
      ions and organic acids. The results reveal that the H2O2/UV has beneficial effect
      on mineralization than O3 only for degradation of Acid Yellow 61 solution and it
      is possible for enhancement of method efficiency by taking longer reaction time
      and addition of high concentration of oxidants.

PMID- 11590761
TI  - Reduced-glutathione concentrations in Boleophthalmus pectinirostris tissues
      exposed to benzo(a)pyrene.
AB  - The concentrations of reduced-glutathione (GSH) in liver and ovary of
      Boleophthalmus pectinirostris are quantified. The concentrations of GSH in the
      ovary are much higher than that of GSH in the liver(nearly 3 times of the liver).
      The study also investigates the changes of GSH contents in the two organs while
      the fishes were exposed to benzo(a)pyrene(BaP) at concentrations of 0, 0.05, 0.2
      and 0.5 mg/L respectively for up to a week. The concentrations of GSH in the
      liver of BaP-exposed fish increased significantly with dose, whereas the
      concentrations of GSH in the ovary decreased significantly compared to controls.
      The results suggested that both the liver and the ovary are the primary organ in
      BaP metabolism, and that the changes of GSH levels may represent an adaptive
      response or toxic effect to BaP exposure.

PMID- 11590762
TI  - Combined effects of two sulfonylurea herbicides on soil microbial biomass and N
      mineralization.
AB  - The interaction effect of two sulfonylurea herbicides, bensulfuron-methyl (B) and
      metsulfuron-methyl(M), were tested on microbial biomass C, N, N-mineralization
      and C/N ratio in a loamy sand soil. The herbicides were applied at various levels
      of: control (B0M0), 0.01 and 0.01 (B1M1), 0.01 and 0.1 (B1M2), and 0.01 and 1.0
      (B1M3) microgram/g soil. Determinations of soil microbial biomass-C, N and N
      mineralization contents were carried out at 1, 3, 5, 7, 10, 15, 25 and 45 days
      after herbicides application. The results showed that the soil microbial biomass
      C (Cmic) and microbial biomass-N (Nmic) decreased consistently with the
      increasing rates of herbicides. The results further indicated that B1M1 and B1M2
      caused a significant reduction in Cmic and Nmic within first 10 and 7 days of
      incubation, respectively, as compared with the control. These reductions in Cmic
      and Nmic were also significant (P = 0.05) with B1M3 application especially within
      first 15 days of incubation. A significant reduction in N-mineralization (N-min)
      was observed with high doses (B1M2, B1M3) of herbicides within first 5 days of
      incubation, while low rate (B1M1) failed to produce any significant effect. An
      increase in the soil microbial biomass C:N ratio was also noted.

PMID- 11590763
TI  - Comparative studies on utilizing nitrogen capacity between two macroalgae
      Gracilaria tenuistipitata var. liui (rhodophyta) and Ulva pertusa (chlorophyta).
      I. Nitrogen storage under nitrogen enrichment and starvation.
AB  - This paper deals with the N storage of Gracilaria tenuistipitata var. liui and
      Ulva pertusa under ammonium enrichment and starvation. After 10 days of ammonium
      enrichment, ammonium NH4+, free amino acid (FAA), protein (pro), chlorophyll
      (Chl), phycoerythrin (PE) and total dissolved nitrogen (TDN) of the two
      macroalgae increased significantly. Total nitrogen (TN) increased significantly
      from 3.65% to 5.78% dry weight of G. tenuistipitata var. liui and 2.82% to 5.07%
      dw of U. pertusa, respectively. Protein and FAA were the most important N storage
      pools in the macroalgae. During N-starvation period, individual N pools of the
      two species were depleted at exponential rates. Each N pool in U. pertusa
      decreased more rapidly than in G. tenuistipitata, var. liui and the latter was
      able to sustain fast growth for more time (> 20 days) than U. pertusa. N demands
      for supporting growth were different between the two species, U. pertusa grew
      more rapidly and had higher N demands than G. tenuistipitata var. liui did.

PMID- 11590764
TI  - Comparative studies on utilizing nitrogen capacity between two macroalgae
      Gracilaria tenuistipitata var. liui (rhodophyta) and Ulva pertusa (chlorophyta).
      II. Feedback controls of intracellular nitrogen pools on nitrogen uptake.
AB  - The potential feedback by intracellular nitrogen pools on maximum N uptake (NH4+)
      rate were determined for Gracilaria tenuistipitata var. liui and Ulva pertusa.
      The results of correlation matrix analyzing showed that the surge uptake of
      ammonium seemed related to rapid changes in small intracellular pools of
      inorganic nitrogen or small peptide and amino acids rather than to changes in TN
      content of the macroalgae. The assimilation rates of nitrogen of U. pertusa and
      G. tenuistipitata increased slowly during N starvation and were mainly regulated
      by amino acids and some incorporation of amino acids into macromolecules. From
      ecological point of view, the fast-growing and uptaking nutrient U. pertusa is
      more suitable to improve water quality in integrated shrimp culture ponds in
      which external nutrient supplies are usually high and constant during the culture
      period, while G. tenuistipitata var. liui is more suitable to be polycultured in
      a waters with intermittence supply of nutrients.

PMID- 11590765
TI  - An ecosystem-based understanding and analysis for SENCE toward sustainable
      development.
AB  - There is a need to find a comprehensive approach focusing on the conflicts
      between economical growth and environmental protection. Chinese scholars advocate
      a comprehensive ecosystem viewpoint named social-economic-natural complex
      ecosystem(SENCE). The kernel of the concept lies in the hierarchical structure of
      SENCE, through which methods from ecological network can be useful to the
      compound system. The author gives a schema depicting its structure, following a
      model analysis to help understand the reliance of economy on ecosystem. It is
      obvious that more actions should be done to strive for sustainable development.

PMID- 11590766
TI  - Prevention of debris flow disasters on Chengdu-Kunming Railway.
AB  - Chengdu-Kunming Railway is an important transport line on southwestern China.
      However, this railway's safety is often threatened by debris flows. How to
      effectively forecast and alarm the debris flow disasters and reduce the losses is
      the aim to study the prevention system in this paper. The factors to cause or
      influence debris flow are divided into four parts--the basin environmental
      factors, the basin meteoric factors, the prevention work's elements and the flood
      relief work's elements, and the prevention system is made up of three models--a
      judgment model to assess the debris flow gully's seriousness, a forecast model to
      predict the debris flow's occurrence and an alarm model to evaluate the debris
      flow's disaster. Afterwards, a concise structure chart is worked out and verified
      by the field data from Chengdu-Kunming Railway. This prevention system will
      provide beneficial reference for the debris flow's monitoring network to be
      executed on Chengdu-Kunming Railway.

PMID- 11590767
TI  - Excessive Cu and Zn affecting on distribution of the metals and activities of
      glycolytic and nitrogen incorporating key enzymes in mycelia of ectomycorrhizal
      fungi Suillus bovinus.
AB  - Concentration of copper and zinc in isolated Suillus bovinus mycelia, used
      nutrient solution and 0.5 mol/L EDTA mycelia washing solution were measured to
      investigate the distribution of heavy metals in mycelia growth in excess copper
      or zinc nutrient solution. Treated with zinc, most of added zinc maintained in
      used solution, and 9.8%/14.6% was in/on mycelia in treatment, and in treatment 2
      was 3.9%/8.0% in/on mycelia. In the copper applications, copper stimulated in
      more than on mycelia, i.e., 25.9%/4.5% in/on mycelia in treatment, and 7%/18.8%
      in/on mycelia while most of copper retained in used nutrient solution. Certain
      amount of copper or zinc uptake by mycelia led to pronounced influence on
      glycolysis and nitrogen incorporating process of Suillus bovinus, while the
      tested enzymes kept constant in treatment. In crude extracts of copper treatment
      2 mycelia, activities of HK, PFK and GS were inhibited and decrease to 63%, 48%
      and 38% and GIDH increased by 68% of the control, respectively. The behaviors of
      these tested enzymes toward zinc corresponded in general with that towards
      copper. The potential protection of Suillus bovinus for its host plant under
      excess copper or zinc threaten was discussed.

PMID- 11590768
TI  - Treatment of turtle-breeding wastewater and domestic fecal sewage with soil
      cultivating system.
AB  - Turtle-breeding wastewater and domestic fecal sewage were treated by means of
      soil cultivating system. Results indicated that more than 50% CODCr and BOD5 of
      wastewaters were removed, removal rates of NH4(+)-N could reach about 70%-80%,
      but PO4(3-) could not be removed. The thesis analyzed functional mechanisms for
      pollutants and put forward main elements affecting treatment efficiencies, thus
      provided conditions for further research.

PMID- 11590769
TI  - Design of policy mechanism to promote cleaner production in China.
AB  - In order to promote cleaner production in China, a package of policy options was
      presented based on the identification of the barriers encountered in the CP
      demonstration project and the effectiveness and feasibility of policy options for
      the CP implementation were analyzed. Furthermore, the policy mechanism framework
      was given, which composes of compulsory, economic incentive, social pressure and
      supportive function. Finally, the implementation strategy of the policy
      mechanism, in which the emphasis will be changed from compulsory policy options
      towards economic and social pressure policy options, was proposed.

PMID- 11590770
TI  - Cadmium status in Egypt.
AB  - It is inferred from these studies that releases of Cd are still increasing and it
      is recommended that measures must be taken to reduce emissions of cadmium. Any
      cadmium discharged into the Egyptian environment may move from one compartment to
      another at varying rates, resulting in an accumulation in compartments such as
      soils and biota. Such accumulation can be expected to increase with continued
      emissions, and attention should be given to all sources of cadmium, natural as
      well as anthropogenic especially in the industrial cities in Egypt. Cadmium
      present in sewage, as well as industrial effluent (also, other liquid and solid
      wastes) and sewage sludge will increase levels in soils and is expected to
      contribute to dietary levels and body burdens. The current information indicates
      that such effects may have to be evaluated over long periods of time, possibly as
      long as 50-100 years.

PMID- 11590771
TI  - Photodegradation of alpha-naphthaleneacetic acid in aqueous solution.
AB  - Kinetic processes of alpha-naphthaleneacetic acid (NAA) photolysis were studied
      under different conditions. The results showed that the ultraviolet light was
      more effective than fluorescent light in promoting degradation, and the
      degradation of NAA under ultraviolet light followed the first order kinetics with
      the photolysis rate constant of 1.15 x 10(-2) min-1 and half-life time (t1/2) of
      60 min. Further, it was proved that the photolysis rate was higher in the
      presence of oxygen, titanium dioxide (TiO2), and low pH (acidic solution). At
      last, two photolysis intermediates were identified by GC-MS and possible
      photolysis pathways were proposed.

PMID- 11590772
TI  - Cleaning method of the oil field wastewater treatment by UF process.
AB  - This article introduces experiments and researches of polysulphone
      ultrafiltration membrane's effect on oil field polluted water and approaches
      renewing oil field polluted water and approaches renewing of membrane's flux by
      different detergents and cleaning method. Good result has been achieved by doing
      experiments and the renewal rate of membrane is over 90%.

PMID- 11590773
TI  - Ability of Agrogyron elongatum to accumulate the single metal of cadmium, copper,
      nickel and lead and root exudation of organic acids.
AB  - Agrogyron elongatum were grown in nutrient solution containing moderate to high
      amounts of separate heavy metal of Cd, Cu, Ni and Pb in a greenhouse for a 9-day.
      Cd, Cu, Ni and Pb generally led to decrease in the elongation of roots although
      the length of seedlings exposed to Cd and Pb at 0.05 and 0.5 mg/L showed to be
      slightly greater than that of controls. Of the four metals in the experiment, Pb
      was absorbed and accumulated to the highest level, with the concentrations of
      92,754 mg/kg dry weight (DW) in roots and 11,683 mg/kg DW in shoots. Cd was
      moderately accumulated in Agrogyron elongatum, but the maximum bioaccumulation
      coefficients (BCs) for roots and shoots were observed. The patterns for Cu and Ni
      uptake and distribution in plants differed from those of Pb and Cd, as it was
      showed that the shoot accumulation of Cu and Ni was significantly higher than in
      roots. A. elongatum had the highest Ni concentration in shoots (30,261 mg/kg DW)
      at the external concentration of 250 mg/L. Cu ranked second, with a shoot
      concentration of 12,230 mg/kg DW when 50 mg/L Cu in solution was applied. For the
      four trace elements tested, the highest concentrations in shoots decreased by the
      order of Ni > Cu > Pb > Cd (mg/kg DW), and those in roots were Pb > Cd > Ni > Cu
      (mg/kg DW). Malic, oxalic and citric acids exuded by roots exposed to 1 and 50
      mg/L of the metals were detected. Release of organic acids from plants
      significantly differed among the metal treatments. Cu was most effectively in
      inducing root exudation of the three types of organic acids. Cd, and Ni were also
      the inducers of secretion of malic and oxalic acids. With reference of Pb, a
      small amounts of malic and oxalic acids were detected in the root exudates, but
      few quantities of citric acid were found. However, no correlation between
      alternations in root exudation of organic acids and metal accumulation could be
      established.

PMID- 11590774
TI  - Effects of cultivation on N2O emission and seasonal quantitative variations of
      related microbes in a temperate grassland soil.
AB  - Laboratory and in situ experiments were done to investigate the influences of
      cultivation on temperate semi-arid grassland (for 17 years spring wheat planted
      once every two years without fertilisation) on soil N2O emission and quantitative
      variations of related soil microbes. In the laboratory (25 degrees C and soil
      moisture 18%), cultivation increased soil transformations of fertilizer nitrogen
      (100 micrograms N/g as NaNO3, urea, or as urea with dicyandiamide 1 microgram
      N/g). The N2O emissions from the cultivated and uncultivated soils with or
      without nitrogen additions were relatively low, and mainly originated from the
      nitrification. The soil N2O emission due to cultivation decreased somewhat upon
      no fertilization or NaNO3 addition, but significantly upon urea addition. The
      role of dicyandiamide as nitrification inhibitor was only considerable in the
      cultivated soil, and had small influence on decreasing N2O emission in the two
      soils. The influence of cultivation on soil N2O emission was also reflected by
      the number variations of microbes related with soil nitrogen transformation in
      the two soils. Compared to the uncultivated grassland, in situ ammonifiers and
      denitrifiers in the cultivated grassland quantitatively averagely increased, and
      aerobic no-symbiotic azotobacters were quantitatively similar, leading to the
      continued decrease of organic matter content and the decrease of N2O emission
      from the cultivated grassland soil.

PMID- 11590775
TI  - Extraction kinetics of phenol with N, N-di (1-methyl-heptyl) acetamide-kerosene
      using hollow fiber membrane extractor.
AB  - Extraction kinetics of phenol with N,N-di(1-methyl-heptyl) acetamide-kerosene
      using hollow fiber membrane extractor has been studied. The rate regularities and
      kinetic types of forward and backward extraction were obtained respectively by
      determining the forward and backward extraction rate under various experimental
      conditions. The mass transfer mechanism was discussed. Both the forward and
      backward extraction of phenol might be controlled by diffusion processes, and the
      diffusion resistance for both forward and backward extraction mainly exists in
      aqueous phase. In addition, ways to optimize the extraction process of phenol
      were discussed as well.

PMID- 11590776
TI  - AIDS risk is high among young people. Do you have all the facts about HIV?

PMID- 11590777
TI  - More patients seek drugs through ADAPs, creating $50 million deficit.
AB  - The national AIDS Drug Assistance Program (ADAP) is $50 million short of averting
      an emergency this summer as states continue to see increases in the number of
      people applying for HIV medications through the program. A few states already
      have waiting lists, but many more might experience difficulties beginning in
      June, ADAP officials say. Meanwhile, congressional efforts to pass a Medicare
      drug benefit could have a positive effect on ADAPs, which have some clients who
      would be eligible for Medicare coverage, but this solution is a long way from
      becoming a reality.

PMID- 11590778
TI  - Medicare drug bill could lend boost to ADAPs.
AB  - Although it's still a long way from becoming a reality, a Medicare prescription
      drug bill could be one solution to funding problems experienced by AIDS Drugs
      Assistance Programs (ADAPs), whose client lists are growing faster than their
      funding. While Medicaid expansions through waiver programs would also be useful,
      those types of efforts require committed state governments and completion of a
      lengthy bureaucratic process. And as the recent National ADAP Monitoring Project
      Report notes, federal-level initiatives to allow states to expand Medicaid
      coverage to low-income, non-disabled people living with HIV have not succeeded.

PMID- 11590779
TI  - Location strongest factor in getting ADAP help.
AB  - Uninsured HIV-infected people in New York who earn less than $44,000 per year,
      which is more than 500% of the federal poverty level, may choose from six
      protease inhibitors, three non-nucleosides, 16 opportunistic infection
      prophylaxis drugs, and 408 other medications from the state AIDS Drug Assistance
      Program (ADAP), according to the 2001 National ADAP Monitoring Project Report. In
      other states, however, the selection is much slimmer.

PMID- 11590780
TI  - Even with other options, patients overuse ERs.
AB  - A California study shows that clinicians need to educate HIV-infected patients
      about when to contact their physicians instead of automatically going to the
      emergency room when faced with a health crisis. Patients often use the emergency
      department instead of visiting their regular doctor, even for common symptoms
      such as tension headaches, concludes the study published in the December 2000
      issue of the Journal of General Internal Medicine.

PMID- 11590781
TI  - Special report: Caribbean's HIV epidemic. New partnership will try to reduce
      infections, deaths.
AB  - While the conscience of industrialized nations are awakening to the AIDS pandemic
      in sub-Saharan Africa, most people, even in the United States, are unaware that
      the Caribbean has the world's second-highest prevalence of HIV infection. A new
      Pan-Caribbean Partnership, formed earlier this year, is designed to bring
      attention to the Caribbean's HIV epidemic, and it will help Caribbean governments
      and organizations meet the challenges of treating HIV-infected people and
      preventing HIV infection.

PMID- 11590782
TI  - AIDS vaccine efforts have followed long, bumpy road.
AB  - Author Jon Cohen discusses the arduous journey taken by researchers and others
      working to develop an AIDS vaccine. In his new book, Shots in the Dark: The
      Wayward Search for an AIDS Vaccine, Cohen documents the frustration that many in
      the HIV community feel regarding the lack of cohesive planning that has gone into
      the AIDS vaccine search.

PMID- 11590783
TI  - HIV academy sets criteria for 'HIV/AIDS specialist'.
AB  - The new American Academy of HIV Medicine of Washington, DC, has established
      standards for clinicians who specialize in treating HIV/AIDS patients. To be
      designated an HIV/AIDS specialist, a clinician first needs to be state-licensed
      as a physician, nurse practitioner, physician assistant, or doctor of
      pharmacology.

PMID- 11590784
TI  - New dietary guidelines give practical advice for healthier living.

PMID- 11590785
TI  - Precision in public health protection. A woman's life's work in radiation.

PMID- 11590786
TI  - Make no mistake! Medical errors can be deadly serious.

PMID- 11590787
TI  - Human gene therapy. Harsh lessons, high hopes.

PMID- 11590788
TI  - New fetal monitoring device keeps better watch on baby.

PMID- 11590789
TI  - User fees for faster drug reviews. Are they helping or hurting the public health?

PMID- 11590790
TI  - Advisory committees. FDA's primary stakeholders have a say.

PMID- 11590791
TI  - FDA lets air out of medical gas company.

PMID- 11590792
TI  - New treatment approved for severe premenstrual symptoms.

PMID- 11590793
TI  - New cancer drug approved for some leukemia-patients.

PMID- 11590795
TI  - Gene therapy researchers react to field's pitfalls and promises.

PMID- 11590798
TI  - Sealant makes lungs air-tight.

PMID- 11590799
TI  - Living skin substitute can heal diabetic foot ulcer wounds.

PMID- 11590803
TI  - Pig ears, cow hooves, other dried pet treats can make you ill.

PMID- 11590804
TI  - Reusing medical devices. Ensuring safety the second time around.

PMID- 11590805
TI  - Indicators of pathologic stage of prostate cancer and their use in clinical
      practice.
AB  - Pathologic stage is the most reliable means of predicting the likelihood of
      curable prostate cancer at the time of definitive treatment. Its prediction is of
      the greatest importance to individuals with clinically localized disease,
      principally because of the therapeutic and prognostic implications. Multivariate
      models integrating variables that can be derived from clinical and pathologic
      assessment have been shown to be reliable and useful in urologic practice. Among
      these variables, the combination of clinical stage, serum PSA, and biopsy Gleason
      score provides reliable assessment of the risk for extraprostatic disease that
      can be used readily for counseling individual patients. Other biopsy-derived
      parameters may contribute additional information, but their value in multivariate
      analysis has not been validated in a multi-institutional setting. The development
      of new prognostic markers is a priority objective in current research to
      distinguish patients in whom cancer cannot be controlled by surgical treatment.
      For patients undergoing radical prostatectomy, definitive pathologic stage
      certainly will remain an important prognostic factor; therefore, clinical
      practice will continue to be determined by its accurate prediction.

PMID- 11590806
TI  - The role of imaging studies and molecular markers for selecting candidates for
      radical prostatectomy.
AB  - For the typical patient who has newly diagnosed prostate cancer, clinically organ
      confined disease of moderate grade, and a PSA less than 10 ng/mL, the current
      role of imaging studies and molecular biomarkers is limited. Bone scans are not
      necessary for newly diagnosed men with a PSA less than 10 ng/mL in the absence of
      bone pain. Similarly, abdominal and pelvic CT scanning rarely provides any useful
      diagnostic or staging information when the PSA is less the 20 ng/mL and is
      indicated rarely. Endorectal coil MR imaging adds staging information for
      patients with a PSA between 10 and 20 ng/mL, a Gleason score of 7 or less, and
      50% or more positive biopsies on a sextant sampling. Indium 111 capromab
      pendetide scanning (ProstaScint) is FDA-approved to evaluate newly diagnosed
      patients at high risk for metastases. These patients have a Gleason score of 7 or
      greater and a PSA greater than 20 ng/mL, a Gleason score of 8 to 10 regardless of
      the PSA value, or clinical stage T3 disease and a Gleason score of 6 or greater.
      RT-PCR testing of blood or bone marrow for prostate-specific or prostate cancer
      specific gene expression, or "molecular staging," is a promising technique whose
      current use is still investigational. Much useful information may be gained by
      careful study of prostate needle biopsy material. Aside from current Gleason
      grading and the number or percentage of cores involved with cancer, no molecular
      biomarker is approved for clinical use. p27, p53, bcl-2, Ki-67 (MIB-1), and the
      assessment of neovascularity hold promise, but prospective multicenter studies
      are needed. In the long-term, multiple gene expression profiling of biopsy
      material using gene chips may revolutionize the care of patients with prostate
      cancer and those who elect radical prostatectomy.

PMID- 11590807
TI  - Practical surgical anatomy for radical prostatectomy.
AB  - Practical guidelines in surgical anatomy for radical prostatectomy can be
      summarized as follows: 1. There is significant individual variation in the
      anatomy of the male pelvis. 2. The prostate is covered anteriorly by a prominent
      detrusor apron. 3. Prostates vary with respect to size and shape. 4. BPH
      compresses and flattens the peripheral zone. 5. In reality, the puboprostatic
      ligaments are pubovesical ligaments. 6. The dorsal vein complex of the penis is a
      neurovascular plexus of veins, arteries, and nerves situated primarily ventral to
      the prostate and urethra. 7. The urethra from the verumontanum to the penile bulb
      is sphincteric, with its smooth muscle and elastic tissue components primarily
      responsible for postprostatectomy urinary continence. 8. Multiple micropedicles
      tether the neurovascular bundles along the entire posterolateral aspect of the
      prostate.

PMID- 11590808
TI  - Indications for pelvic lymphadenectomy in prostate cancer.
AB  - Clearly, pelvic lymphadenectomy can provide important staging information in the
      management of prostate cancer, but this benefit is counterbalanced by a modest
      increase in morbidity and the significant cost of the procedure. It is difficult
      to provide universal recommendations concerning the indications for pelvic
      lymphadenectomy. Part of the problem lies in the fact that urologists perform
      pelvic lymphadenectomy for several different reasons. Some surgeons perform
      pelvic lymphadenectomy to better counsel patients after radical prostatectomy
      about their risk for disease progression and for planning adjuvant radiotherapy
      or hormonal therapy. For these surgeons, preoperative clinical staging parameters
      do not exclude patients from pelvic lymphadenectomy, and frozen section analysis
      intraoperatively provides no useful information. Alternatively, the staging
      information from pelvic lymphadenectomy can be used to justify cancellation of
      the subsequent prostatectomy should regional spread of prostate cancer be
      identified, sparing the patient the morbidity of an unnecessary radical
      prostatectomy. With this approach, despite the false-negative rate of up to 30%,
      the expense of frozen section analysis seems justified. For this second group of
      surgeons, the problem becomes balancing the modest morbidity and cost of pelvic
      lymphadenectomy against the probability that nodal spread of prostate cancer will
      be missed if the procedure is omitted. The authors consider a greater than 4%
      risk for missing regional disease to be unacceptable in this setting. Following
      this assumption, Table 3 outlines parameters for clinical stage, Gleason score,
      and preoperative PSA within which pelvic lymphadenectomy is indicated. These
      recommendations are based on [table: see text] predictions from the Partin
      nomogram, which has been validated using a series of over 4000 patients. For the
      large number of patients with clinical T1c disease and a preoperative PSA less
      than 10 ng/mL, bilateral pelvic lymphadenectomy is indicated only if prostate
      biopsy identifies tumor of Gleason grade 4 or higher. For lower-grade tumors in
      this patient population, the risk for nodal metastasis was less than 5% in the
      Johns Hopkins and Mayo Clinic series of over 5800 patients with prostate cancer.
      For a large pool of patients, the several thousand dollar cost of pelvic
      lymphadenectomy and the risk for injury to the obturator nerves and vessels, the
      formation of lymphoceles, and chronic genital edema can be eliminated with low
      risk. A nomogram-based approach provides only a starting point for a decision
      analysis framework to determine whether the surgeon should perform
      lymphadenectomy at the time of radical prostatectomy because current nomograms
      predict only lymph node positivity. In a decision analysis framework, some
      patient and physician value is derived from a negative lymphadenectomy. Moreover,
      the morbidity associated with pelvic lymphadenectomy and the potential
      inconvenience associated with treating such morbidity also would be factored into
      the decision. Consequently, a decision analysis framework that takes into account
      prognostic value, costs, morbidity, and health state uses ultimately will provide
      the most informative method for determining when pelvic lymphadenectomy is
      indicated in patients with prostate cancer.

PMID- 11590809
TI  - Radical retropubic prostatectomy. Preoperative management.
AB  - The morbidity of radical prostatectomy is minimized by identifying men who are at
      significant cardiovascular risk and excluding them from the procedure.
      Preoperative management designed to minimize surgical and medical complications
      and exposure to allogenic blood products increases the benefit-to-risk ratio of
      radical prostatectomy over other treatment options for localized prostate cancer.

PMID- 11590810
TI  - Radical retropubic prostatectomy.
AB  - Historically, radical prostatectomy is a surgical technique associated with
      significant morbidity. The ability to minimize intraoperative bleeding and
      preserve continence and potency requires a comprehensive understanding of pelvic
      anatomy, meticulous surgical technique, and appropriate surgical instruments. The
      anatomic radical retropubic prostatectomy first described by Walsh in 1982
      represents a technique in evolution. The detailed surgical approach for anatomic
      radical retropubic prostatectomy described in this article represents the
      author's technique that has been developed after performing over 2,000 radical
      prostatectomies since 1986. The step by step illustrations and description of
      technique are designed to aid the urologic surgeon develop an efficient approach
      to this surgical procedure.

PMID- 11590811
TI  - The technique of radical perineal prostatectomy.
AB  - The resurgence of the radical perineal prostatectomy for the treatment of
      localized prostate cancer has been facilitated by the current emphasis on
      reducing medical costs, the identification of more cases of localized disease,
      the selected use of lymphadenectomy, and the use of laparoscopic techniques to
      perform node sampling. This technique provides a cost-effective, low-morbidity,
      and efficacious means of treating localized prostate cancer.

PMID- 11590812
TI  - Indications and contraindications for nerve-sparing radical prostatectomy.
AB  - Nerve-sparing radical prostatectomy can be performed safely in most men
      undergoing radical prostatectomy. As is true in many aspects of prostate cancer
      diagnosis and therapy, the key element is patient selection. With many prostate
      tumors diagnosed at an earlier stage, the authors have seen a shift toward more
      favorable pathologic findings at the time of surgery. Concomitant with the
      success of early detection of prostate cancer is the realization that men are
      younger at the time of diagnosis and more interested in preserving sexual
      function. This article has described factors associated with an increased risk
      for extraprostatic tumor and, subsequently, an increased possibility of
      postprostatectomy cancer recurrence. Except for the previously mentioned absolute
      contraindications, none of these factors, by themselves, should be used to
      exclude a patient from nerve-sparing prostatectomy. Instead, meticulous attention
      must be given to the surgical dissection. If any doubt remains regarding residual
      tumor, the surgeon should err on the side of caution and remove the neurovascular
      bundle. The use of standardized intraoperative frozen-section analysis can help
      guide these decisions. The patient must be informed before surgery regarding the
      risks of nerve-sparing surgery, the potency rates of the surgeon, and the
      possibility that, to ensure adequate cancer control, the nerves may be sacrificed
      despite any preoperative optimism favoring the potential for their salvage.

PMID- 11590813
TI  - Salvage radical prostatectomy.
AB  - Although technically challenging, salvage prostatectomy for radiorecurrent
      prostate cancer is an effective option in carefully selected patients and offers
      the best chance for cure and long-term survival. Alternatively,
      cystoprostatectomy may be indicated in some patients who have a small capacity
      fibrotic bladder or intractable voiding symptoms related to radiation cystitis.
      Good long-term results can be expected in this patient group; however,
      exenterative surgery in patients with locally advanced disease is associated with
      comparably inferior results and should not be advocated. If cystectomy is
      necessary, orthotopic urinary diversion can be performed safely in young
      motivated patients who wish to maintain a better quality of life with associated
      morbidity. Although the higher rate of incontinence and impotence after salvage
      procedures may detract from the quality of life, the impact of these long-term
      complications on the patient's overall well-being is less than previously
      believed, and most patients are satisfied with their treatment outcome and adjust
      well to the circumstances, accepting some increased degree of morbidity. This
      observation emphasizes the value of careful preoperative counseling and the
      discussion of treatment options and outcomes, which also should incorporate
      quality of life issues.

PMID- 11590814
TI  - Long-term biochemical disease-free and cancer-specific survival following
      anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience.
AB  - In a large series of 2404 men with a mean follow-up of 6.3 plus or minus 4.2
      years (range, 1-17) after anatomic RRP for clinically localized prostate cancer,
      412 men (17%) have recurred. A detectable PSA was the only evidence of recurrence
      in 9.7%, whereas 1.7% and 5.8% had local recurrence and distant metastasis,
      respectively. The overall actuarial 5-, 10-, and 15-year recurrence-free survival
      rates for these men were 84%, 74%, and 66%, respectively. As demonstrated in the
      authors' previous reports, the actuarial likelihood of a postoperative recurrence
      increased with advancing clinical stage, Gleason-score, preoperative PSA level,
      and pathologic stage. Subdivision of men with Gleason 7 tumors resulted in better
      stratification. There was a similar actuarial likelihood of postoperative
      recurrence for men with Gleason 4 + 3 and Gleason score 8 to 10 disease. The
      actuarial rate of recurrence of tumor for men with Gleason 3 + 4 disease was
      statistically different from the rate for men with Gleason score 6 or Gleason 4 +
      3 disease. The overall actuarial metastasis-free survival rates at 5, 10, and 15
      years were 96%, 90%, and 82%, respectively. The overall actuarial cancer-specific
      survival rates at 5, 10, and 15 years were 99%, 96%, and 90%, respectively. This
      study provides long-term outcome of patients with clinically localized cancer who
      underwent RRP between 1982 and 1999. Recognizing that this long-term study
      includes many patients with more advanced disease diagnosed before the PSA era,
      caution must be exercised in comparing these results with the outcomes for
      cohorts of patients treated since 1989. Anatomic RRP is an effective way to
      manage clinically localized prostate cancer. Excellent long-term results can be
      obtained with RRP for early stage disease. The proportion of men with early stage
      prostate cancer will continue to increase with wide use of serum PSA testing and
      digital rectal examination.

PMID- 11590815
TI  - Pathologic assessment of the surgical specimen.
AB  - Despite the wealth of information obtained by conventional histology, long-term
      studies are needed to provide novel information on the correlation of pathologic
      findings with prognosis. Findings need to be correlated not only with PSA
      progression but with the more clinically important parameters of distant
      metastases and survival. Although conventional histology still will have a role
      in the evaluation of prostate cancer at radical prostatectomy and its correlation
      with outcome, it undoubtedly will be augmented by newer techniques. These
      developments must be approached critically and rationally to determine whether
      they provide additional prognostic information beyond that currently available
      using more conventional parameters.

PMID- 11590816
TI  - Prevention and management of incontinence following radical prostatectomy.
AB  - Incontinence after radical prostatectomy can have a significant impact on quality
      of life. Although several risk factors have been identified, the surgical
      technique and advancing age are important factors associated with
      postprostatectomy incontinence. Despite advances in technique, incontinence still
      occurs in a small group of men. Sphincteric dysfunction is the most common cause
      of postradical prostatectomy incontinence, but bladder dysfunction cannot be
      discounted. Treatments range from conservative to surgical and should be tailored
      to the individual based on the degree of bother and patient willingness to accept
      different therapeutic options.

PMID- 11590817
TI  - Prevention and management of erectile dysfunction following radical
      prostatectomy.
AB  - Most studies indicate general satisfaction rates of greater than 80% after
      radical retropubic prostatectomy. Nonetheless, erectile dysfunction remains the
      most common problem postoperatively, with rates ranging from 100% to 10%
      depending on the experience of the surgeon, the frequency with which he or she
      performs the surgery, the nerve-sparing nature of the procedure, the stage of the
      disease, and the age and preoperative potency of the patient. The natural
      recovery of erection function takes as long as 24 months and can be expedited by
      early treatment with intracorporal injection therapy. The treatment of erectile
      dysfunction after radical retropubic prostatectomy is highly successful despite
      the finding that fewer than 50% of patients seek treatment. Sildenafil does not
      seem to be effective early in the recovery phase but increases in efficacy as the
      nerves recover from intraoperative injury. Other modalities in the early recovery
      phase in the order of increasing effectiveness are intraurethral prostaglandin,
      the vacuum erection device, and intracorporal injection therapy. After 2 years
      from surgery, the recovery of natural function and improved sildenafil
      responsiveness are unlikely, and the implantation of a prosthesis is reasonable
      if other modalities are ineffective or unacceptable for the patient. Animal
      studies and human trials are underway to examine ways to expedite and maximize
      the return of erectile function.

PMID- 11590818
TI  - The role of radiotherapy after radical prostatectomy.
AB  - The results of radiotherapy (RT) as used at the Mayo Clinic are reviewed and
      compared with the available literature. An attempt is made to summarize the risks
      and benefits of RT in these settings. Additionally, avenues of future potential
      investigation are explored.

PMID- 11590819
TI  - Intraoperative, perioperative, and long-term complications of radical
      prostatectomy.
AB  - With improved surgical technique and perioperative care, the intraoperative and
      early postoperative complications of radical prostatectomy have decreased over
      the last 2 decades. Incontinence and impotence are two of the most significant
      long-term complications related to this procedure. Although the wide range of
      incontinence and impotence rates reported has been attributed to multiple
      factors, including the method of data collection and patient selection, it is
      apparent that the surgeon's experience is a significant factor, and that lower
      long-term morbidity can be expected from centers with more experience with
      radical prostatectomies. The impact of long-term complications, including urinary
      and sexual dysfunction, on the quality of life may be less than previously
      reported and should be discussed with patients.

PMID- 11590820
TI  - Laparoscopic radical prostatectomy: is it feasible and reasonable?
AB  - Laparoscopic radical prostatectomy is an extremely challenging procedure for even
      experienced laparoscopic surgeons, and it is not practical to expect most
      urologists to learn the technique. Nevertheless, it is a feasible procedure and
      has short-term results comparable with conventional radical prostatectomy. For
      LRP to be an acceptable and reasonable alternative, the oncologic results must be
      equivalent to the results of RRP, and significant advantages is morbidity
      (hospital stay, pain, incontinence, impotence) must be attained; otherwise, the
      steep learning curve and the additional expense of the procedure make it
      difficult to justify as an alternative therapeutic modality. Beside a reduction
      in the transfusion rate, no other significant advantages of LRP over radical
      prostatectomy have been demonstrated definitively to date. As a result, the role
      of LRP in the management of prostate cancer remains investigational, and patients
      should be informed appropriately. The oncologic results and low morbidity of
      nerve-sparing RRP set a high standard for a laparoscopic technique to equal.

PMID- 11590821
TI  - Laparoscopic augmentation cystoplasty. Surgical technique.
AB  - Laparoscopic enterocystoplasty is technically feasible and successfully emulates
      the established principles of open enterocystoplasty while minimizing operative
      morbidity. As is true in open surgery, various bowel segments can be fashioned
      and anastomosed to the bladder laparoscopically. The increased costs associated
      with laparoscopy and with minimally invasive surgery in general have been a
      significant disadvantage; however, a previous report on the costs of laparoscopic
      procedures concluded that increased surgical experience reduces the surgical time
      and length of hospital stay, thereby decreasing costs. Furthermore, the increased
      use of reusable instruments results in considerable economic benefits.
      Implementation of appropriate cost-saving strategies ultimately will result in
      decreased expenses associated with laparoscopy. Although laparoscopic
      enterocystoplasty is currently a lengthy procedure lasting twice as long as open
      surgery, further technical modifications and increasing experience will continue
      to reduce the surgical time involved. For patients with complex comorbid illness
      who desire the improved quality of life associated with traditional augmentation
      cystoplasty, the reduced morbidity observed in the authors' series of patients
      undergoing a laparoscopic procedure makes this approach an attractive option to
      consider. The authors' initial experience suggests that laparoscopic
      enterocystoplasty has the potential to become a viable alternative to open
      enterocystoplasty.

PMID- 11590822
TI  - Different orthodontic treatment effects in Angle Class III patients.
AB  - The aim of this study was to compare the different treatment effects observed in
      Angle Class III patients treated either exclusively in the primary dentition or
      receiving treatment initiated during the early mixed dentition. 14 patients from
      five families were enrolled in this retrospective study. The treatment course,
      appliances, treatment length and treatment outcomes were compared. The skeletal
      changes were assessed by analyzing cephalometric radiographs taken prior to,
      during and after completion of orthodontic treatment. In those patients receiving
      treatment in the primary dentition only, the course of treatment was more
      continuous and only one appliance had to be used. Moreover, the treatment time
      was shorter compared to those patients starting treatment in the early mixed
      dentition (5.4 +/- 2.1 vs 21.1 +/- 9.7 months). Treatment exclusively in the
      primary dentition showed better dentoalveolar results.

PMID- 11590823
TI  - Tensor analytical evaluation of the effects of a skeletonized activator in the
      treatment of Class II, Division 1 patients.
AB  - PATIENTS AND METHOD: The study covered 40 patients (21 boys and 19 girls) whose
      Class II, Division 1 malocclusion was being treated with a Klammt open activator.
      To illustrate growth changes, tensor analysis was used as a superimposition-free
      comparative technique. At the beginning of treatment for Class II correction, the
      boys had a mean age of 11.3 years and the girls a mean age of 10.1 years.
      Patients were evaluated on admission and on attaining normal occlusion. 58 boys
      and 63 girls participating in a growth study at Kings College School of Medicine
      and Dentistry, London, served as controls. RESULTS: Prior to treatment the
      participants suffering from Class II, Division 1 malocclusion exhibited distinct
      growth deficits in vertical direction. In the control group, the principal
      direction of mean growth was found to be anterior-inferior. Under the influence
      of the activator, growth was found to develop in the same direction as in the
      controls, so that anterior positioning of the lower jaw and an increase in lower
      facial height were attained.

PMID- 11590824
TI  - Orthodontic space closure without contralateral extraction through mesial
      movement of lower molars in patients with aplastic lower second premolars.
AB  - METHOD AND PATIENTS: A method is presented that allows unilateral space closure
      in patients with aplastic lower second premolars. Based on a straight-wire
      appliance, space closure was achieved with a combination of "push mechanics"
      using the second molar as an anchorage unit and Class II "pull mechanics", thus
      avoiding the application of any distalizing force on the lower incisors. The
      results from 13 consecutively treated subjects (five boys, eight girls, mean age
      12 years and 6 months) were analyzed. RESULTS: Complete bodily space closure was
      achieved in all 13 cases within a mean treatment time of 2 years and 7 months.
      The desired Angle Class III molar relationship of one premolar width (+/- 1/4
      premolar width) on the aplastic side was successful in eleven patients, an
      additional 4.7 mm of space being created for the third molar on the aplastic side
      compared with the contralateral side (p < or = 0.01). However, adverse effects
      could be kept to a minimum, with no method-dependent side effects being recorded
      with regard to canine and molar relationships on the contralateral side, or to
      overbite, overjet, or upper and lower incisor inclination. The mean lower midline
      shift of 0.8 mm was in accordance with the mean distal canine relationship of 1/3
      premolar width on the aplastic side. CONCLUSION: These results confirm that
      orthodontic space closure in cases of unilateral aplastic lower second premolars
      can be performed successfully with the presented treatment method without the
      need for additional premolar extractions, prosthodontic treatment or implants.
      Furthermore, the prognosis for the lower wisdom tooth on the aplastic side is
      improved.

PMID- 11590825
TI  - Suggestion for orthodontic and speech improving measures in CLP patients.
AB  - The objective of the present paper is to describe a soft palate level device, the
      veloretractor, which is a combination of orthodontic appliance and therapeutic
      aid in speech therapy. Its use is demonstrated in a case report of a child with
      complete bilateral cleft lip and palate. Both orthodontic and
      phoniatric/pedaudiologic treatment needs during the course are demonstrated along
      with the treatment results.

PMID- 11590826
TI  - Conditioning of enamel with Nd:YAG and CO2 dental laser systems and with
      phosphoric acid. An in-vitro comparison of the tensile bond strength and the
      morphology of the enamel surface.
AB  - MATERIAL AND METHOD 1: The first stage of a three-stage in-vitro investigation
      used 146 maxillary incisors to identify optimum setting parameters for two CO2
      and Nd:YAG standard laser systems applied in enamel conditioning for bracket
      bonding. RESULTS: 31 of the 75 parameter combinations investigated for the Nd:YAG
      laser and nine of the 71 investigated for the CO2 laser proved appropriate for
      further investigation of tensile strength. MATERIAL AND METHOD 2: In a second
      stage, tensile bond strength for the selected laser settings was determined in
      comparison to the conventional acid-etch technique for a further 210 teeth as the
      control group. RESULTS: The highest average tensile strength for the Nd:YAG laser
      was 4.1 MPa, with comparable values of 3.3 MPa for the CO2 Laser and 4.9 MPa for
      the acid-etch technique. MATERIAL AND METHOD 3: The third stage of the
      investigation involved comparative scanning electron microscopy of enamel surface
      morphology following laser application and acid-etching. RESULTS: The CO2 laser
      was found to produce craters of various dimensions, while the Nd:YAG laser
      produced honeycomb structures regionally similar to enamel samples from the acid
      etch technique. CONCLUSION: The CO2 and Nd:YAG dental lasers tested produce
      enamel conditioning and tensile bond strength sufficient to meet the requirements
      of bracket bonding.

PMID- 11590827
TI  - Comparison of incisor mobility after insertion of canine-to-canine lingual
      retainers bonded to two or to six teeth. A clinical study.
AB  - BACKGROUND: Fixed appliance therapy often extends over several years. Debonding
      is warmly welcomed and is often seen by the patient as the end of treatment. Yet
      both patients and parents often underestimate the importance of the subsequent
      retention period and the speed at which negligence in this treatment phase
      results in relapse. Bonded retainers guarantee excellent long-term stability at
      least while they are in situ. The reliable attachment of lingual retainers with
      modern bonding techniques has led to widespread application of this retention
      method. The present study investigated its influence on tooth mobility and on the
      damping properties of the periodontal tissue, by means of a dynamic measuring
      method (Periotest). PATIENTS AND METHOD: For this purpose two groups with
      mandibular bonded retainers and one control group were formed. The control group
      wore removable retention appliances. In all groups, active treatment with fixed
      appliances had been completed at least half a year before baseline. RESULTS: The
      results showed that bonded retainers had a negative impact on the damping
      properties of the periodontal tissue and thus in the broader sense on tooth
      mobility. Tooth mobility decreased with the number of teeth to which the retainer
      was bonded but remained, as in the control group, within the physiologic range.

PMID- 11590828
TI  - Early treatment of Angle Class II, Division 2 in combination with functional
      therapy of TMJ fracture.

PMID- 11590829
TI  - Cloning and characterization of KLHL5, a novel human gene encoding a kelch
      related protein with a BTB domain.
AB  - Most kelch family proteins contain two conserved domains, the BTB domain and the
      kelch repeat domain. Here we describe the cloning and characterization of a novel
      human KLHL5 gene. The 3488 bp cDNA encodes a kelch family protein homologous to
      the Drosophila kelch protein. It also contains the two conserved domains.
      Northern blot analysis reveals a single transcript. It is abundantly expressed in
      ovary, adrenal gland, and thyroid and less abundantly expressed in trachea,
      prostate, testis, lymph node, and spinal cord. KLHL5 was mapped to 4p13-4p15.1.

PMID- 11590830
TI  - Differences in charge and kinetic properties of alcohol dehydrogenase 4 from
      C57BL/6 mice compared to other inbred strains are associated with a cysteine120
      to arginine120 substitution.
AB  - Alcohol dehydrogenase class IV (ADH4) participates in retinol metabolism and is
      expressed primarily in ocular, digestive, and reproductive tissues of the mouse.
      A naturally occurring genetic variant in C57BL/6J mice results in a faster
      migrating ADH4 enzyme during electrophoresis when compared to other non-C57BJ/6J
      strains. The C57BL/6 ADH4 gene coding sequence is found to have two nucleotide
      substitutions when compared to the gene from C3HeB/FeJ mice. The substitution in
      exon 5 encodes Arg120 instead of Cys120 in C57BL/6 ADH4 polypeptide; that would
      account for the protein electrophoretic phenotype. Arg120 is present in all
      published mammalian ADH4 sequences but is only in a limited number of mouse
      strains. The Arg120 residue is part of the outer loop of the substrate binding
      pocket and appears to have an effect on the affinity of the enzyme for several
      substrates.

PMID- 11590831
TI  - Three types of polymorphisms in exon 14 in porcine Mx1 gene.
AB  - Much is known about the antiviral activity of Mx proteins in species such as
      mouse and human. In the mouse, loss of resistability to influenza virus has been
      shown to be due to specific polymorphisms in the Mx gene. This gene is therefore
      an interesting candidate gene for disease resistance in farm animals. The porcine
      Mx1 gene has already been identified and characterized based on its homology with
      mouse Mx1; however, until now no evidence of polymorphisms in the porcine gene
      has been reported. In this study, we have found two new polymorphisms in exon 14
      of porcine Mx1 by DNA sequencing and confirmed their presence in different
      breeds, using polymerase chain reaction (PCR)-restriction fragment length
      polymorphisms (RFLP) with NarI and NaeI restriction enzymes. On the basis of the
      deduced amino acid sequence, one allele contains a deletion that may result in a
      frameshift to yield several amino acid substitutions and extension of the
      carboxyl terminal region of Mx1 protein. The deletion allele, Mx1c, was found to
      be segregating in Landrace, Berkshire, Duroc, Hampshire, and Yucatan miniature
      pig. A second point mutation, Mx1b, was detected in Meishan and two Vietnamese
      native pig breeds. All other breeds tested were fixed for the Mx1a allele that is
      identical to the sequence reported previously. It will be interesting to
      determine if the Mx1c deletion is associated with variation in resistance to the
      myxovirus family in the pig.

PMID- 11590832
TI  - Marker assisted selection of bacterial blight resistance genes in rice.
AB  - Bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae is one of the most
      important diseases affecting rice production in Asia. We were interested in
      surveying rice genotypes that are popularly used in the Indian breeding program
      for conferring resistance to bacterial blight, using 11 STMS and 6 STS markers.
      The basis of selection of these DNA markers was their close linkage to xa5, xa13,
      and Xa21 genes and their positions on the rice genetic map relative to bacterial
      blight resistance genes. Eight lines were found to contain the xa5 gene while two
      lines contained Xa21 gene and none of the lines contained the xa13 gene with the
      exception of its near-isogenic line. Using the polymorphic markers obtained in
      the initial survey, marker-assisted selection was performed in the F3 population
      of a cross between IR-64 and IET-14444 to detect lines containing multiple
      resistance genes. Of the 59 progeny lines analyzed, eight lines contained both
      the resistance genes, xa5 and Xa4.

PMID- 11590833
TI  - Low genetic variation of Penaeus chinensis as revealed by mitochondrial COI and
      16S rRNA gene sequences.

PMID- 11590834
TI  - Unusual isozyme patterns of glucose-6-phosphate isomerase in Polydora brevipalpa
      (Polychaeta: Spionidae).

PMID- 11590835
TI  - Clinical classification of pulmonary hypertension.
AB  - Pulmonary hypertension is a prevalent disease of multiple etiologies. Over the
      years, different attempts at nomenclature and classification, largely based on
      morphologic findings at autopsy, have met with limited success. Recent advances
      in medical and surgical treatment, and the promise of effective approaches to
      prevention, have prompted the development of a clinical classification designed
      to take advantage of the new promising interventions. This article traces the
      growth of understanding of the pulmonary hypertensive diseases that has enabled
      the development of a clinical classification oriented towards prevention and
      treatment.

PMID- 11590836
TI  - The pathology of pulmonary artery hypertension.
AB  - The pathologic features of primary pulmonary hypertension (PPH) are well known
      but its pathogenesis remains uncertain. In the first section, this chapter
      outlines the characteristic structural changes of PPH. The second section deals
      with the pathogenesis of these changes drawing on animal models of chronic
      pulmonary hypertension. The third section deals with phenotypic alterations in
      cells from the wall of the pulmonary artery of hypertensive animals. The recent
      identification of a germlike mutation in the BMPR2 gene in patients with PPH
      provides a novel opportunity to further our understanding of the pathogenesis of
      this disease.

PMID- 11590837
TI  - The pathobiology of pulmonary hypertension. Endothelium.
AB  - Dysfunctional endothelial cells have a central and critical role in the
      initiation and progression of severe pulmonary hypertension. The elucidation of
      the mechanisms involved in the control of endothelial cell proliferation and cell
      death in the pulmonary vasculature, therefore, is fundamentally important in the
      pathogenesis of severe pulmonary hypertension and of great interest for a better
      understanding of endothelial cell biology. Because the intravascular growth of
      endothelial cells resulting in tumorlets is unique to severe pulmonary
      hypertension, this phenomenon can teach researchers about the factors involved in
      the formation and maintenance of the normal endothelial cell monolayer. Clearly,
      in severe pulmonary hypertension, the "law of the endothelial cell monolayer" has
      been broken. The ultimate level of such a control is at the altered gene
      expression pattern that is conducive to endothelial cell growth and disruption of
      pulmonary blood flow. Secondary pulmonary hypertension certainly also is
      associated with proliferated pulmonary endothelial cells and plexiform lesions
      that are histologically indistinguishable from those in PPH. What is then the
      difference in the mechanisms of endothelial cell proliferation between primary
      and secondary pulmonary hypertension? The authors believe that PPH is a disease
      caused by somatic mutations in key angiogenesis- or apoptosis-related genes such
      as the TGF-beta receptor-2 and Bax. The loss of these important cell growth
      control mechanisms allows for the clonal expansion of endothelial cells from a
      single cell that has acquired a selective growth advantage. On the other hand,
      the proliferated endothelial cells in secondary pulmonary hypertension are
      polyclonal. It follows from this finding that local (vascular) factor(s) (such as
      increased shear stress), rather than mutations, play a major role in triggering
      endothelial cell proliferation. In PPH and secondary pulmonary hypertension, the
      researcher can postulate that the pulmonary vascular bed contains progenitor-like
      cells with the capacity of dysregulated growth. The main difference in the
      pathogenesis of primary and secondary pulmonary endothelial cell proliferation
      therefore may be the initial mechanism involved in the recruitment of an
      endothelial progenitor-like cell. In PPH, anorexigen-associated, and familial
      PPH, the proliferation of endothelial cells occurs from a mutated single cell,
      whereas in secondary pulmonary hypertension, several progenitor-like cells would
      be activated to grow. The abnormal endothelial cells in both forms of severe
      pulmonary hypertension expand because of the expression of angiogenesis-related
      molecules such as VEGF, VEGFR-2, HIF-1 alpha, and HIF-beta. Also important for
      the expansion of these cells is the down-regulation of expression of apoptosis
      related mediators such as TGF-beta receptor-2 or Bax. The success of any therapy
      for severe pulmonary hypertension requires that the underlying process of
      endothelial cell proliferation could be controlled or reversed.

PMID- 11590838
TI  - The pathobiology of pulmonary hypertension. Smooth muscle cells and ion channels.
AB  - Chronic hypoxic pulmonary arterial hypertension, APAH, and PPAH are characterized
      by vasoconstriction and vascular remodeling and are associated with decreased Kv
      currents in PA smooth muscle cells. Although Kv2.1 is less well studied, it seems
      that Kv1.5 is particularly important in the pulmonary circulation in animals and
      humans because it has been implicated in physiologic phenomena (HPV) and all of
      the aforementioned pulmonary hypertensive disorders. This occurrence is perhaps
      because of the fact that it controls Em in the PA smooth muscle cells and it has
      a short turnover half time. It is also certain that the pathogenesis of PPAH is
      multifactorial and not a result of a single abnormality. The recently discovered
      "PPAH gene" in chromosome 2q in patients with familial PPAH (6%-12% of patients)
      does not seem to encode for any Kv channels. Kv1.5 abnormalities, however, are
      likely to be a strong predisposing factor that, in association with others such
      as endothelial dysfunction, [figure: see text] anorexigen use, or viral
      infections, will initiate a process that eventually leads to PPAH. The selective
      Kv1.5 down-regulation leaves wide open the door to replacement gene therapy in
      pulmonary hypertension research.

PMID- 11590839
TI  - Pathobiology of pulmonary hypertension. Extracellular matrix.
AB  - Changes in the extracellular matrix underlie the structural and functional
      abnormalities in the vessel wall that lead to progressive pulmonary vascular
      disease. Studies are reviewed aimed at addressing the cellular and molecular
      programs that regulate the production of the extracellular matrix describing new
      ways to arrest proliferation and migration of smooth muscle cells and to induce
      apoptosis. The latter can lead to the reversal of pathology at least in
      experimental animal models.

PMID- 11590840
TI  - Pathobiology of pulmonary hypertension. The role of platelets and thrombosis.
AB  - With the rare exceptions of PAH associated with antiphospholipid antibodies,
      genetic platelet dysfunction, or inherited deficiencies of antithrombotic
      pathways, the thrombotic lesions are secondary, but frequently occurring, in most
      cases of primary or secondary PAH. Pulmonary arterial hypertension is associated
      with thrombotic lesions and persistent vasoconstriction and structural remodeling
      of PA. Activated platelets interact with the PA wall and may contribute to the
      functional and structural alterations of pulmonary vessels by releasing
      vasoactive factors and mitogenic mediators.

PMID- 11590842
TI  - Genetics of primary pulmonary hypertension.
AB  - Familial primary pulmonary hypertension (FPPH) is a well described clinical
      entity in which the disease occurs in at least two first degree relatives. It is
      clinically and pathologically indistinguishable from sporadic PPH. Mutations in
      the gene which encodes bone morphogenetic receptor 2 have recently been
      discovered in familial and sporadic PPH. This review discusses the basic clinical
      and genetic features of FPPH, and describes the research that led to the
      discovery of the disease-causing gene. Potential mechanisms of disease are also
      discussed, as well as implications for future investigations.

PMID- 11590841
TI  - Risk factors for pulmonary arterial hypertension.
AB  - The present limitations in knowledge of the potential risk factors for PPH
      undoubtedly are attributable to the facts that PPH is a rare disease with an
      unknown pathogenesis and lacking large case series. Moreover, definite
      epidemiologic data are rare and ideally should be obtained from epidemiologic
      surveys such as large case-control studies. The increased incidence of the
      disease in young women, the familial cases, the association with autoimmune
      disorders, and the recent discovery that mutation of the PPH1 gene may not be
      restricted to familial PPH support the hypothesis that the development of
      pulmonary hypertension likely implies an individual susceptibility or
      predisposition, which is probably genetically determined. It is also now commonly
      believed that the development of pulmonary hypertension in some of these
      predisposed individuals could be hastened or precipitated by various expression
      factors (some of them yet unrecognized), such as ingestion of certain drugs or
      diets, portal hypertension, or HIV infection.

PMID- 11590843
TI  - The assessment of pulmonary hypertension.
AB  - The goals of evaluating pulmonary hypertension are detection, definition of
      severity and the nature of the hemodynamic lesion and its consequences, diagnosis
      of causal or associated conditions, and determination of optimal therapy. These
      objectives are reliably achieved by a disciplined approach employing multiple
      diagnostic tools. This chapter outlines the fundamental background and guidelines
      for assessing pulmonary hypertension, including consideration of several new and
      less frequently used methods to elucidate the physiologic mechanism. Since early
      detection and treatment may improve outcome, screening higher risk populations
      and a diagnostic approach to the milder spectrum of pulmonary hypertension is
      also addressed.

PMID- 11590844
TI  - Medical therapy of pulmonary hypertension. An overview of treatment and goals.
AB  - Therapeutic medical advances over the past two decades have resulted in
      significant improvements in the outcome for patients with various forms of
      pulmonary arterial hypertension. As the current understanding of the pathology
      and pathobiology of pulmonary arterial hypertension has moved forward, rationale
      for additional therapeutic modalities with novel therapeutic agents has led to
      increased clinical investigations. A brief overview of the pathology and
      pathobiology is presented as background for an introduction to the current
      medical therapy for pulmonary arterial hypertension as well as the goals for
      future treatment.

PMID- 11590845
TI  - Medical therapy of pulmonary hypertension. Conventional therapies.
AB  - The 1-, 3-, and 5-year survival rates of the patients included in the National
      Institute of Health Registry on Primary Pulmonary Hypertension were 77%, 41%, and
      27% respectively. It is unclear to what extent better applied conventional
      therapy contributes to improved survival rates that now are reported with calcium
      channel blockers, prostacyclin, or even transplantation. To date, by far the most
      favorable results are reported with high-dose calcium-channel blockers combined
      with anticoagulant therapy, with survival rates at 3 years approximately 100%. It
      has to be emphasized, however, that such exceptionally favorable results are to
      be expected only in a small minority of patients who should not be considered to
      be cured because, sooner or later, their disease will continue to evolve. Further
      improvements obviously are needed for most patients with PAH. Interesting
      developments are likely in the coming years, with new multidrug approaches to
      control pulmonary vasoreactivity and remodeling and, hopefully, also with
      progress in lung transplantation. The past 2 decades have witnessed important
      progress in the treatment of PAH. Although significant improvements in quality of
      life and survival rate have been obtained with prostacyclin therapy, and better
      perspectives now are offered with atrial septostomy and lung transplantation,
      conventional therapy also has evolved. Patients now are counseled more adequately
      regarding how to remain physically active while avoiding exercise-induced anginal
      pain or syncope. Invasive and potentially risky medical procedures have been
      restricted in favor of noninvasive and functional evaluations whenever possible.
      Risk factors such as appetite suppressants, pregnancy, and hypobaric hypoxia are
      now better appreciated. The indications of supplemental oxygen, inotropic agents,
      and diuretics have been refined based on improved pathophysiologic understanding.
      Most patients now benefit from anticoagulant therapy with coumarin derivatives,
      although some uncertainty remains about the optimal international normalized
      ratio to be achieved. Safer acute reversibility testing now is performed with
      fewer and shorter-acting agents that are more specific to the pulmonary
      circulation to select the small proportion of patients who benefit from long-term
      high-dose calcium-channel blocker therapy.

PMID- 11590846
TI  - Medical therapy of pulmonary hypertension. The prostacyclins.
AB  - Prostacyclin is a substance produced by endothelial cells that induces
      vasodilation and inhibition of platelet aggregation and of vascular cell
      migration and proliferation. A dysregulation of the prostacyclin metabolic
      pathways has been shown in patients with pulmonary arterial hypertension. The
      clinical use of prostacyclin has been made possible by the synthesis of stable
      analogues that possesses different pharmacokinetic properties but share similar
      pharmacodynamic effects. The greatest experience has been collected with
      intravenous epoprostenol while other compounds like subcutaneous UT-15, inhaled
      iloprost and oral beraprost are currently in different stages of clinical
      development. Although favorable results have been reported for each compound,
      different benefit-to-side effects profiles characterize the various modalities of
      the administration.

PMID- 11590848
TI  - Atrial septostomy for pulmonary hypertension.
AB  - Atrial septostomy represents an additional, promising strategy in the treatment
      of severe PPH. Experience with this procedure still is limited; however, based on
      analyses of the worldwide experience, several general conclusions and
      recommendations can be made. 1. Atrial septostomy can be performed successfully
      in selected patients with advanced pulmonary vascular disease. 2. Patients with
      primary pulmonary hypertension who have undergone successful AS have shown: a
      significant clinical improvement beneficial and long-lasting hemodynamic effects
      at rest a trend toward improved survival 3. The procedure-related mortality of
      the collective experience is high (16%). Several recommendations can be made to
      minimize the risk: [figure: see text] Atrial septostomy should be attempted only
      in institutions with an established track record in the treatment of advanced
      pulmonary hypertension, where septostomy is performed with low morbidity. Atrial
      septostomy should not be performed in patients in whom death is impending or who
      have severe right ventricular failure and are on maximal cardiorespiratory
      support. An mRAP greater than 20 mm Hg, PVR index greater than 55 u/m2, and a
      predicted 1-year survival less than 40% are significant predictors of procedure
      related death. Before cardiac catheterization, patients should have an acceptable
      baseline systemic oxygen saturation (> 90% in room air) and optimized cardiac
      function (adequate right heart filling pressure, additional inotropic support if
      necessary). During cardiac catheterization, the following are mandatory:
      Supplemental oxygen Mild sedation to prevent anxiety Careful monitoring of
      variables (left atrial pressure, SaO2, and mRAP) Step by step procedure After AS,
      it is important to optimize oxygen delivery. Transfusion of packed red blood
      cells or erythropoietin (before and following the procedure, if needed) may be
      necessary to increase oxygen content. 4. Because the disease process in PPH is
      unaffected by the procedure (late deaths), the long-term effects of an AS must be
      considered to be palliative. 5. Despite its risk, AS may represent a viable
      alternative for selected patients with severe PPH. Indications for the procedure
      may include: Recurrent syncope or right ventricular failure, despite maximal
      medical therapy, including oral calcium-channel blockers or continuous
      intravenous prostacyclin (Fig. 11) As a bridge to transplantation When no other
      option exists.

PMID- 11590847
TI  - New and experimental therapies for pulmonary hypertension.
AB  - Advances in the understanding of the molecular and cellular pathogeneses of PPH
      have led clinicians beyond simple pulmonary vasodilation as the only treatment
      for PPH and to a realization that what were previously believed to be
      irreversible vascular lesions may, in fact, be reversible. The development of
      agents that target the known endothelial and nonendothelial defects in patients
      with PPH is well underway. Clinicians are witnessing an exciting new era for
      physicians and patients dealing with this disease.

PMID- 11590849
TI  - Chronic thromboembolic pulmonary hypertension.
AB  - Remarkable advances have occurred over the past 2 decades in the diagnostic
      approach, surgical management, and postoperative care of patients afflicted with
      chronic thromboembolic pulmonary hypertension. Despite these advances, a great
      deal needs to be achieved if the morbidity and mortality of the disease process
      are to be reduced further. First, the preliminary insights that have been
      achieved into the natural history of the disease must be defined further. The
      level of pulmonary hypertension encountered in most patients with chronic
      thromboembolic pulmonary hypertension at the time of initial clinical recognition
      cannot be reached on an acute basis. Gradual hemodynamic progression, therefore,
      must occur over time. The basis for this progression, why it occurs in certain
      patients and not others, following an acute thromboembolic event and why it seems
      to occur over months in certain patients and over decades in others, remain
      entirely speculative. It is possible that the overall extent of central pulmonary
      vascular obstruction represents the primary pathophysiologic determinant of
      disease progression. Given the lack of correlation between the degree of central
      thromboembolic obstruction and hemodynamic impairment in certain patients,
      however, it is also possible that other factors, such as the circulating
      vasoconstrictors, the development of a hypertensive pulmonary arteriopathy, an
      individual genetic predisposition to pulmonary hypertension, or the compensatory
      adaptations of the right ventricle, contribute to the extent and rate of disease
      progression. By identifying and sequentially evaluating patients with persistent
      pulmonary vascular obstruction or pulmonary hypertension following an acute
      thromboembolic event, valuable insights into the natural history of
      thromboembolic pulmonary hypertension and other variants of pulmonary
      hypertension might be achieved. It is also important to recognize that the
      development of chronic thromboembolic pulmonary hypertension represents a failure
      in the long-term management or follow-up surveillance of those with documented
      acute thromboembolic disease. Recent insights into the recurrent nature of acute
      thromboembolic disease and its potential for only partial resolution in a number
      of afflicted individuals suggest that a repeat perfusion scan and, if abnormal,
      an echocardiogram be performed at the time of anticipated discontinuation of
      anticoagulation in patients with documented pulmonary embolic disease. Although
      the cost-effectiveness of this approach has been questioned in the past, recent
      data suggest that doing so would help identify that subset of patients with
      unresolved embolism, provide additional information regarding the optimal
      duration of anticoagulation, and provide a new baseline study for patients in
      whom anticoagulation is discontinued and who subsequently present with suspected
      embolic recurrence. Improved diagnostic techniques are also necessary if the
      mortal risk of thromboendarterectomy is to be reduced. Even in the setting of a
      broad experiential base, prognostic uncertainty exists in approximately 10% of
      patients before operative intervention. Because many of these patients will
      benefit from the procedure, and because many are ineligible for transplantation
      for reason of age or other restriction, it has been the authors' practice to
      offer surgery to these patients, although at an assumed higher risk. To not do so
      would be to deny a potentially lifesaving procedure to many who would benefit and
      who might be left without an effective therapeutic alternative. The ability to
      better define the group of patients who will not benefit from surgery, however,
      would spare those patients the morbid and mortal risks of the procedure and
      provide a basis for the investigation of other therapeutic alternatives such as
      pulmonary vasodilating agents. Finally, this patient population offers a unique
      opportunity to enhance understanding of the pathophysiologic mechanisms involved
      in acute lung injury. The population involved is uniform, the predisposing event
      is consistent, the time of onset is predictable, and, compared with other
      populations at risk for acute lung injury, the presence of confounding variables
      is negligible. It also provides a unique opportunity to evaluate pharmacologic
      interventions designed to prevent or diminish the occurrence of acute lung injury
      and postoperative management strategies designed to minimize its impact.

PMID- 11590850
TI  - Lung transplantation for primary pulmonary hypertension.
AB  - Recent progress in medical therapies has diminished the role of transplantation
      in the management of PPH during the past decade. Drug therapy is not effective in
      some patients, responses to therapy are not sustained over time in others, and
      drug side effects eventually limit the benefits of treatment in a few more. Lung
      transplantation therefore ultimately is the only alternative for patients whose
      PPH is severe and cannot be managed medically. Choosing the right patient as a
      transplant candidate and the right time to make the initial referral to a
      transplant center are the crucial initial steps in the transplantation process,
      and the long waiting time before transplantation must be integrated into this
      decision. The outcome of lung and heart-lung transplantation for PHH has been
      good but sobering. Functional recovery has been excellent, but long-term survival
      results have been limited by the high prevalence of chronic allograft rejection.

PMID- 11590852
TI  - 5th circuit first to acknowledge disability-based harassment.

PMID- 11590851
TI  - Report of the Xenotransplantation Surveillance Workshop. Infection control
      database and sample archiving.
AB  - An enhanced xenotransplantation surveillance system is one of many precautionary
      measures to reduce infectious disease risks to recipients, their offspring and
      third parties. A critical review of the literature along with an analysis of the
      survey results and discussion suggests that the current regulatory framework in
      Canada may benefit from the development of an interim policy on
      xenotransplantation clinical trials to deal with enhanced surveillance issues.
      Additionally, international harmonization on the surveillance of
      xenotransplantation clinical trials to reduce the infectious disease risks to
      recipients and third parties also seems warranted. Although an appraisal of the
      literature on PERVs seems to indicate that there is at least a theoretical risk
      of PERV transmission to humans through xenotransplantation, recent evidence
      suggests this risk might be minimized in the near future. For example, there is
      preliminary evidence from Dr. Clive Patience, a principal scientist at
      BioTransplant Inc., that pig herds could be bred that do not produce infective,
      replication-competent PERVs. However, whether special breeding or cloning of
      animals may, in fact, eliminate the production of replication-competent
      endogenous or endemic viruses remains to be seen. There remain several important
      issues about pre-clinical safety assessment, including the requirement for
      studies in NHPs (efficacy and safety) versus infectious disease risks
      (transmissibility of pig infectious agents to primates) and minimal follow-up
      times in animals, before clinical trials are considered in Canada. In summary,
      national and international cooperation is needed to effectively devise and adopt
      enhanced surveillance measures for xenotransplantation that will identify,
      contain, and minimize infectious disease risks to recipients, their offspring and
      third parties worldwide. A number of problems and points to consider have been
      outlined in this report for future national and international discussion.

PMID- 11590853
TI  - Bush appoints national AIDS policy coordinator.

PMID- 11590854
TI  - States report changes in HIV/AIDS policy and statistics.

PMID- 11590855
TI  - Prison head may be liable for revealing inmate's HIV status.

PMID- 11590856
TI  - Global alliance formed to fight AIDS on international front.

PMID- 11590857
TI  - HHS awards $846.7 million in HIV/AIDS care grants.

PMID- 11590858
TI  - Illinois Senate fails to pass nonprescription syringe bill.

PMID- 11590859
TI  - Nursing agency loses right to Medicare reimbursement.

PMID- 11590860
TI  - Calif. hit with largest-ever class action for prison conditions.

PMID- 11590861
TI  - Hepatitis C: a greater corrections risk than HIV?

PMID- 11590862
TI  - ADAP spending, patient base grow but budget shortfalls persist.

PMID- 11590863
TI  - [Occupational risk for HIV and HBV: KAP survey in a sample of dentists].

PMID- 11590864
TI  - [Legionellosis associated with travel: the situation in Italy in 1995-1999].

PMID- 11590865
TI  - [Epidemiologic survey on the prevalence of arterial hypertension in the island of
      Ponza].

PMID- 11590866
TI  - [Osteoporosis: risk factors and biochemical indicators].

PMID- 11590867
TI  - [Evaluation of the sensitivity of measles and mumps notification through
      surveillance by "sentinel" pediatricians].

PMID- 11590868
TI  - [Incidence of caries in a sample of 3-7-year old children in Rome who were not
      included in population prevention programs].

PMID- 11590869
TI  - [Mortality among residents of a region with high environmental risk].

PMID- 11590870
TI  - [Dietary supplements and doping in a population of non-professional athletes:
      prevalence study].

PMID- 11590871
TI  - [Microclimate parameters in operating rooms].

PMID- 11590872
TI  - [Quality of hospital discharge data in Piedmont].

PMID- 11590873
TI  - [Quality measurement and control of contracted external services].

PMID- 11590875
TI  - N-3 fatty acids and cardiac function after myocardial infarction in Denmark.
AB  - In order to evaluate the effect of marine n-3 polyunsaturated fatty acids (n-3
      PUFA) on systolic left ventricular function, we investigated the effect of daily
      supplementation with 5.2 g n-3 PUFA for 12 weeks in 55 patients with a recent
      myocardial infarction in a double blind placebo-controlled design. Left
      ventricular function was assessed by transthoracal echo-cardiography and plasma
      concentration of proANP and N-terminal proANP. No effect of n-3 PUFA could be
      demonstrated on these indices of left ventricular function.

PMID- 11590874
TI  - Sulphur dioxide exposure and lung function in a Norwegian and Russian population
      living close to a nickel smelter.
AB  - The Norwegian-Russian border area is polluted by sulphur dioxide (SO2) emitted
      from a Russian nickel smelter in the city of Nikel. We studied the effects of
      daily variations in SO2 on the lung function levels of people on both sides of
      the border. A cross-sectional population-based study was performed among adults
      in Sor-Varanger, Norway (n = 3438) and Nikel, Russia (n = 1613). All subjects
      were assigned 24 h mean SO2 concentrations for their day of screening and the day
      before on basis of residency. The SO2-concentrations were compared with the daily
      recordings of forced expiratory volume in one second expressed as percentage of
      the predicted value (FEV1% predicted). In Sor-Varanger, no significant
      associations between SO2 and FEV1% predicted were found. In Nikel, FEV1%
      predicted was exceeded non-systematically in some of the exposure categories (10
      50, 50-90, or > 90 micrograms/m3) compared to the reference exposure group (0-10
      micrograms/m3). In conclusion, neither of the study populations suffered from a
      measurable reduction in lung function when SO2 increased above the reference
      level.

PMID- 11590876
TI  - Cardiovascular drugs and the risk of death in acute myocardial infarction in
      northern Sweden MONICA patients.
AB  - PURPOSE: To quantify the impact of cardiovascular drugs used before the acute
      myocardial infarction (AMI) and given during the acute phase on reduction in the
      risk of death during the first 28 days after an AMI. METHODS: The Northern Sweden
      MONICA database on incident AMI was analysed with regard to drug use before and
      during the acute phase of the myocardial infarction and the risk of death within
      the first 28 days. All patients admitted to a hospital in this area with a
      suspected diagnosis of AMI were included in this database. RESULTS: No drugs used
      before and up to the acute myocardial infarction provided protection against
      death in the AMI in this analysis. Among drugs given during the acute phase,
      antiplatelet drugs and betablocking drugs reduced the risk of death in the AMI
      and to a lesser degree, anticoagulants and nitrates provided protection.
      CONCLUSIONS: The administration of antiplatelet drugs and betablockers in the
      acute phase of an AMI substantially reduces the risk of death during the first 28
      days after an AMI for the individual.

PMID- 11590877
TI  - High rates of hospitalisation for bronchiolitis in Inuit children on Baffin
      Island.
AB  - It has been suspected that Inuit Children on Baffin Island suffer from severe,
      recurrent episodes of bronchiolitis, but this has never been documented
      previously. This study is a retrospective chart review of children less than 48
      months of age hospitalised at Baffin Regional Hospital, Nunavut with a diagnosis
      of bronchiolitis over a one year period. This study documented that the admission
      rate for bronchiolitis in the first year of life was 306 per 1000 infants on
      Baffin Island, with an intubation rate of 12.8% in admitted children. One quarter
      of the infants were born prematurely, and half had their first presentation for
      bronchiolitis at less than 3 months of age. Ten of the 78 cases (12.8%) were
      identified as having a positive test for C. trachomatis by EIA, and Respiratory
      syncytial Virus was identified in 14 of 50 (28%) of those tested. This study
      documents that bronchiolitis in Inuit children on Baffin Island is a serious
      health concern and needs to be studied further.

PMID- 11590878
TI  - Teenager injury panorama in northern Sweden.
AB  - OBJECTIVES: To study non-fatal unintentional injuries among teenagers and to
      suggest preventive measures. SETTING: The emergency care unit of the University
      Hospital, Umea, Sweden. METHODS: All injured teenagers (N = 1044) attending the
      emergency care unit during 1991 were asked to answer a questionnaire focusing on
      when, where and how the injury occurred. All available medical records were
      examined. Data were coded according to the Nordic Medico-Statistical Committees
      Classification for Accident Monitoring, NOMESCO, and to the Abbreviated Injury
      Scale, AIS. RESULTS: 1,043 teenagers were treated with sports and transportation
      related injuries as the most common ones. Most injuries were minor (AIS 1),
      transportation related injuries had the highest proportion of non-minor injuries
      (AIS > or = 2), 139 teenagers were admitted for in-patient care. Most injuries
      occurred during leisure/school time. CONCLUSIONS: Sports and transportation
      related injuries were most frequent. Body weight and length differs among
      teenagers, we suggest that teenagers should exercise and play together, not only
      by age, but also to some extent, to height and weight. Curfew laws, a compulsory
      bicycle helmet law are other injury reducing measures suggested.

PMID- 11590879
TI  - Injury mortality risk assessment and targeting the subpopulations for prevention
      in the Northwest Territories, Canada.
AB  - BACKGROUND AND OBJECTIVE: Prevention of injury mortality is a top priority for
      public health in the Northwest Territories, Canada. However, the frequency of
      injury mortality may not be evenly distributed in subgroups. Assessment of
      population relative risk of injury mortality can assist in better targeting of
      prevention programs. METHODS: A population-based case-control study consisting of
      197 cases was used to quantify the relative risks of injury mortality for
      variables age, sex, ethnicity, geographic location and remoteness. RESULTS: A
      multivariate logistic model showed that the odds ratios were 2.90 (95% CI 2.09
      4.03) for males, 3.39 (95% CI 2.55-4.52) for age group 15-64 years, 11.50 (95% CI
      6.47-20.42) for age group over 64 years, 1.51 (95% CI 1.13-2.02) for people in
      remote communities, and 2.04 (95% CI 1.50-2.79) for people above 66 degrees
      latitude. Aboriginal people of Dene and Inuit presented increased risks in the
      stratified analysis by community remoteness and latitude. CONCLUSIONS: Males,
      over age 14, living in remote communities, living in the far north, and being
      aboriginal were at higher risk of injury mortality. Based on the relative risks
      of injury mortality and the population size in each subpopulation, injury
      prevention investments should be extended to remote communities.

PMID- 11590880
TI  - Effect of regular winter swimming on the activity of the sympathoadrenal system
      before and after a single cold water immersion.
AB  - This study deals with the adaptation of the sympathoadrenal responses to an acute
      cold water immersion in ordinary winter swimmers. Hormonal responses were
      determined at the beginning of the winter swimming period in the autumn and after
      regular swimming for one and three months. Water temperature in the river was 10
      degrees C at the beginning and 4 degrees C after one and three months. The mean
      duration of the test immersion was 36 s. Plasma catecholamine levels determined
      before the test immersion decreased with the winter swimming period for one month
      (NA, p < 0.001, A, p < 0.01). The test immersion significantly increased
      noradrenaline levels (p < 0.001). Plasma adrenaline and serum cortisol levels
      were increased or decreased by the immersion. After 1 month's swimming the test
      immersion to 4 degrees C increased noradrenaline to a similar level than the
      immersion to 10 degrees C at the beginning. Regularly practiced winter swimming
      for three months led to diminished catecholamine levels measured immediately
      after the test immersion (p < 0.01). The results suggest that cold adaptation
      induced by winter swimming attenuates the catecholamine responses to cold water.
      Adrenaline responses are also affected by its level prior to the immersion.

PMID- 11590881
TI  - Carbamazepine induced right bundle branch block in a Greenlandic patient.
AB  - A 53 year old Greenlandic male was admitted twice over a period of 4 years with a
      new complete right bundle branch block after ingestion of 10 g and 4 g of
      carbamazepine respectively. In both instances, reversion of intraventricular
      conduction to normal occurred within 72 hours, coinciding with clearance of
      carbamazepine from the blood stream. We recommend routine follow up by ECG of
      patients over the age of 50 treated with carbamazepine.

PMID- 11590882
TI  - Health and Performance in the Cold. Oulu, Finland, May 16-19, 2000.

PMID- 11590883
TI  - Assessment of cold exposure.

PMID- 11590884
TI  - Human cold acclimatisation and acclimation.

PMID- 11590885
TI  - Mental and cognitive performance in the cold.
AB  - Vigilance, attention, memory, and motivation are essential to adapting to the
      physiological changes that occur with prolonged exposure to the cold and to
      avoiding both the environmental hazards associated with cold and the health
      related consequences of these hazards. This paper summarizes the effects of cold
      temperatures on cognitive performance and mood. Although the effects of
      hypothermic-induced cold temperatures on cognitive performance and mood have been
      well documented, evidence of nonhypothermic effects has been inconsistent. There
      is evidence of a dose-response relation involving decrements in cognitive
      performance with respect to decline in core body temperature and complexity of
      tasks performed. However, it is unclear whether these effects are due to
      distraction or increased arousal. Likewise, further research is required to test
      the efficacy of existing and proposed pharmacologic and nutritional
      countermeasures.

PMID- 11590886
TI  - Frank Pauls (1914-2001).

PMID- 11590887
TI  - The acrosomic reaction in stallion spermatozoa: inductive effect of the mare
      preovulatory follicular fluid.
AB  - In the female genital tract, spermatozoa must undergo capacitation and acrosome
      reaction prior to fertilization. A number of factors may induce physiological
      acrosome reaction assayed in vitro. The aims of this study are to determine the
      inductive effect of the preovulatory follicular fluid on the sperm acrosomal
      status in the equine, once some characteristics of the follicular fluid during
      folliculogenesis had been evaluated. The spermatozoa were obtained from cauda
      epididymes of adult stallion. Follicular fluid was taken from mare ovarian
      follicles classified according to their diameter. In these fluids, total protein,
      progesterone, estradiol and osmolarity were determined. Afterwards, the effect of
      preovulatory follicular fluid (50%) upon induction of the acrosomic reaction in
      stallion capacitated spermatozoa was assayed. Results show that during
      folliculogenesis the ratio progesterone/estrogen is below 1. In large
      preovulatory follicles, there is a sharp increase of progesterone, reaching a
      ratio progesterone/estrogen close to 4. Protein concentration and osmolarity
      increase together with follicular development, being osmolarity very high at the
      preovulatory stage. Follicular fluid--in vitro--increases the percentage of
      spermatozoa with acrosome reaction, maintaining high rates of vitality and
      motility. The characteristics of follicular fluid undergo dynamic changes during
      the folliculogenesis, such as steroid level, protein concentration and
      osmolarity. These events may play a role in the reproductive process in vivo,
      considering that in vitro the follicular fluid is a very effective inductor of
      the acrosome reaction, with optimum levels of vitality and motility.

PMID- 11590888
TI  - Ultrastructural studies on the respiratory tract of mice inoculated intranasally
      with L. fermentum.
AB  - The ultrastructural modifications of the respiratory tract of mice produced by
      the intranasally inoculated L. fermentum was evaluated. The genus Lactobacillus
      has been largely studied from the probiotic effect point of view in different
      ecological systems. Lactobacilli inoculated in 4 intranasal doses (1 x 10(9)
      CFU/dose) do not produce fundamental changes at the ultrastructural level in the
      organs of the respiratory tract studied. The most important finding was the
      presence of a cellular type with intracellular structures surrounded by membranes
      exhibiting electron dense paracristalline material parallel arranged.

PMID- 11590889
TI  - Embryogenic cell suspensions from different explants and cultivars of Eragrostis
      curvula (Schrad.) Nees.
AB  - The aim of this work was the establishment of embryogenic calli and cell
      suspensions from different explants and cultivars of weeping lovegrass,
      Eragrostis curvula (Schrad.) Nees, to be used as targets for biolistic
      transformation. Calli were initiated from immature inflorescences, seeds,
      embryos, leaf bases and root tips. Modified MS medium (Murashige and Skoog, 1962)
      was used for calli induction and proliferation. Cell suspensions were established
      and maintained in AAF medium (Wang et al., 1993). Morphogenic calli, embryogenic
      cell suspensions of moderate growth rate--consisting mainly of compact
      proembryogenic cell clusters- and green plants were obtained from all the
      explants and cultivars assayed, except root tips. Both, explant and genotype were
      very important factors to be considered in order to obtain a morphogenic response
      and to establish cell suspensions from this grass. The statistical analysis
      detected interaction between both factors, explants and genotypes. Immature
      inflourescences were the best source of explant and Kromdraai was the cultivar
      that showed the best morphogenic response (expressed as the percentage of
      calli/explant and the percentage of calli with green spots--every green spot
      developed into green plants-) with inflourescences, embryos and leaf bases. For
      Morpa and Don Pablo embryos as explants were less responsive than seeds and leaf
      bases. There were no differences in leaf bases for all the three cultivars
      analysed.

PMID- 11590890
TI  - Plant regeneration from Ilex spp. (Aquifoliaceae) in vitro.
AB  - In vitro plant regeneration from nodal segments (containing one axillary bud) of
      seven species of the genus Ilex (I. argentina, I. brevicuspis, I. dumosa, I.
      microdonta, I. pseudoboxus, I. taubertiana and I. theezans) were readily achieved
      through three steps: 1) shoot regeneration by in vitro culture of nodal segments
      in MS medium at 1/4 strength, plus 3% sucrose and 0.65% agar (1/4MS) and 0.5
      microM BA (45 days of culture); 2) Induction of rooting from regenerated shoots
      with 1/4MS (solidified with 2.5 g.L-1 "Phytagel") with 7.3 microM IBA (7 days)
      and, 3) subculture of shoot on a fresh medium (1/4MS lacking plant growth
      regulators) during 21 days. Shoot regeneration of other three species (I.
      aquifolium, I. brasiliensis and I. integerrima) were also obtained by in vitro
      culture of nodal segments. Shoot regeneration of I. aquifolium, I. brasiliensis,
      I. integerrima, I. microdonta, I. pseudoboxus, and I. taubertiana were also
      obtained by culture shoot tips on 1/4MS and 0.5 microM BA. Shoot regeneration
      from meristems of I. argentina, I. brevicuspis, I. dumosa, and I. theezans were
      readily achieved by in vitro culture on the same medium.

PMID- 11590891
TI  - The behavior of sex chromosomes in two human X-autosome translocations: failure
      of extensive X-inactivation spreading.
AB  - Two patients, one adult male and one infant girl, bearing different X-autosome
      translocations, were studied with cytogenetical, ultrastructural and chromosome
      painting techniques. The adult male, is a carrier of a reciprocal, balanced
      translocation involving the X and #2 chromosomes: 46,Y,t(X;2) (q13;p21). This man
      showed infertility with spermatogenesis arrest at the spermatocyte stage.
      Synaptonemal complex analysis at pachytene showed the quadrivalent structure and
      the putative breakage points. Sex-chromatin condensation did not spread towards
      the autosomal regions of the quadrivalent. The female infant showed diminished
      body growth and multiple somatic anomalies. She is a 45,Xp-,t(X;21)(p11;p13)
      carrier, an unbalanced translocation involving chromosomes X and #21, which leads
      to a monosomy of almost all Xp. The translocated #21 is practically complete, and
      its centromere is the active one in the rearranged product. The analysis of
      interphase nuclei with the X-centromere probe shows that the Xq region of the
      rearranged chromosome is the late -replicating and inactive element. However, X
      inactivation does not spread to the attached #21, as shown by the R-banding
      pattern. Thus, both in the male adult and in the female infant there is a barrier
      to the spreading effect of X-chromosome inactivation, which is probably due to
      different mechanisms.

PMID- 11590892
TI  - The calcium chelator BAPTA affects the binding of assembly protein AP-2 to
      membranes.
AB  - Clathrin coated vesicles are involved in receptor-mediated transport. The coat of
      these vesicles is constituted mostly of clathrin and the assembly proteins AP-1
      or AP-2. In the present study using an in vitro binding system, we found that the
      interaction of AP-2 but not AP-1 with membranes diminished when the calcium
      chelating agent BAPTA was added. The maximal inhibitory effect was observed with
      10 mM of the chelating agent. Binding of AP-2 to membranes was recovered by
      adding calcium in a concentration-dependent fashion. Binding was also affected
      when the membranes were previously treated with BAPTA and then washed. However,
      other chelating agents such as EDTA or EGTA, as well as the zinc chelating TPEN,
      did not have any effect on the binding. From these results we postulate a role
      for calcium in regulating the assembly-disassembly cycle of adaptors in the
      formation of clathrin coated vesicles.

PMID- 11590893
TI  - Curiosity, forbidden knowledge, and the reformation of natural philosophy in
      early modern England.
AB  - From the patristic period to the beginning of the seventeenth century curiosity
      was regarded as an intellectual vice. Curious individuals were considered to be
      proud and "puffed up," and the objects of their investigations were deemed
      illicit, dispute engendering, unknowable, or useless. Seventeenth-century
      projects for the advancement of learning had to distance themselves from
      curiosity and its dubious fruits or, alternatively, enhance the moral status of
      the curious sensibility. Francis Bacon's proposals for the instauration of
      knowledge were an integral part of a process by which curiosity underwent a
      remarkable transformation from vice to virtue over the course of the seventeenth
      century. The changing fortunes of this human propensity highlight the morally
      charged nature of early modern debates over the status of natural philosophy and
      the particular virtues required of its practitioners. The rehabilitation of
      curiosity was a crucial element in the objectification of scientific knowledge
      and led to a gradual shift of focus away from the moral qualities of
      investigators and the propriety of particular objects of knowledge to specific
      procedures and methods.

PMID- 11590894
TI  - Plant hormones in war and peace. Science, industry, and government in the
      development of herbicides in 1940s America.
AB  - This essay describes the emergence of "hormone" herbicides from academic plant
      physiology research in America in the late 1930s and 1940s, attending especially
      to the role of interactions between university scientists, industrial concerns,
      and government (particularly agricultural) agencies. The importance of an
      intellectual shift among the physiologists to viewing hormones as plant toxins
      rather than growth stimulators, spurred by wartime events, is discussed. The
      essay concludes by exploring the postwar marketing of these hormones as
      agrichemicals and as lawn treatments for suburban consumers, placing these in the
      economic and ecological context of other contemporary developments in farming
      technique.

PMID- 11590895
TI  - Curing cut or ritual mutilation? Some remarks on the practice of female and male
      circumcision in Graeco-Roman Egypt.
AB  - Ancient texts and archaeological artifacts provide the starting point for a
      review of the surgical aspects of female genital mutilation (FGM) in ancient
      Egypt. Analysis of the ancient surgical procedure incorporates modern experience
      on the subject as well as ancient literary and cultural perspectives. Comparison
      of FGM with ancient Egyptian male circumcision and consideration of motivations
      for the practice contribute to our understanding of FGM. In particular, the
      documented association between male circumcision and generative ability suggests
      a novel comparison with a natural process in the female--the breaking of the
      hymen on first intromission--and ultimately a new hypothesis for the origin of
      ancient FGM.

PMID- 11590896
TI  - Clinical course of patients with IgA nephropathy between combined treatment of
      immunosuppressive agents and ACE inhibitor and ACE inhibitor alone.
AB  - BACKGROUND: It has not been clear whether immunosuppressive therapy favorably
      influences renal function and proteinuria in IgA nephropathy (IgAN). Angiotensin
      converting enzyme inhibitor (ACEi) has an anti-proteinuric effect in IgAN. A
      retrospective study was done to see whether the addition of immunosuppressive
      therapy to ACEi produces a more excellent anti-proteinuric effect and preserves
      better renal function than ACEi alone. METHODS: A total of 49 patients with
      proteinuria > 1.0 g/day and serum creatinine concentrations < 1.5 mg/dL were
      followed-up from at least 1 year to 9 years. Among them, 25 patients were treated
      with the combination of cyclophosphamide, prednisolone and ACEi while the other
      24 were treated with ACEi alone. RESULTS: The combination therapy or ACEi alone
      both reduced proteinuria with significant value (the combination group: from 5.74
      +/- 5.08 to 2.29 +/- 2.77 g/day, ACEi group: from 3.85 +/- 2.54 to 1.68 +/- 1.91
      g/day), while no significant differences in reduction of proteinuria were noticed
      between the two groups. There was no significant elevation of serum creatinine in
      both groups during follow-up (the combination group: from 0.91 +/- 0.20 to 1.03
      +/- 0.38 mg/dL, ACEi group: from 0.93 +/- 0.27 to 0.99 +/- 0.37 mg/dL). This
      study showed no significant differences in the change in slope of 1/serum
      creatinine levels during the follow-up period between the two groups. CONCLUSION:
      We conclude that immunosuppressive therapy may not be beneficial in patients with
      proteinuric IgAN. ACEi may be a valuable therapeutic agent avoiding serious side
      effects of immunosuppressive agents.

PMID- 11590897
TI  - The predictive parameters of erythropoietin hyporesponsiveness in patients on
      continuous ambulatory peritoneal dialysis.
AB  - BACKGROUND: The present study was aimed at investigating the predictive
      parameters of erythropoietin (epoetin) hyporesponsiveness in patients on
      continuous ambulatory peritoneal dialysis (CAPD). METHODS: We studied 40 patients
      with end-stage renal disease who had been receiving CAPD for at least 6 months
      and epoetin therapy for at least more than 2 months. Pearson's simple correlation
      and multiple stepwise linear regression analysis was used to discover what
      parameter can predict epoetin resistance. We expressed epoetin resistance index
      (ERI) as weekly epoetin dose/hematocrit/body weight'. The dose of epoetin is
      titrated by about 25% every 2 to 4 weeks to maintain a target hematocrit level
      between 33% and 36%. RESULTS: We analyzed the relationship between ERI and other
      predictive parameters by Pearson's correlation. These results showed ERI has a
      statistically significant correlation with transferrin saturation (TS) (r = 
      0.327, p = 0.042), total weekly Kt/Vurea (r = -0.423, p = 0.018), serum albumin
      level (r = -0.458, p = 0.003), normalized protein catabolic rate (nPCR) (r = 
      0.479, p = 0.006), normalized protein equivalent of total nitrogen appearance
      (nPNA) (r = -0.488, p = 0.005) and serum C-reactive protein (CRP) (r = 0.332, p =
      0.036). Regression analysis was performed using stepwise linear regression for
      multiple variables to discover the most independent variable which is correlated
      with ERI. ERI was entered as a dependent variable, whereas the other parameters
      (age, duration of peritoneal dialysis, serum albumin level, CRP, serum ferritin,
      total weekly Kt/Vurea, nPCR, nPNA, serum iPTH, serum aluminium, TS) were entered
      as independent variables. This analysis showed CRP is the most significant
      variable and, if CRP is excluded, nPNA is the significant variable. CRP has a
      statistically significant correlation with serum albumin level (r = -0.418, p =
      0.007) and total weekly Kt/Vurea (r = -0.366, p = 0.043). High CRP group has more
      increased level of ERI (p < 0.05), age (p < 0.05) and serum creatinine level (p <
      0.05) than normal control, but more decreased level of serum albumin (p < 0.01)
      and serum iron levels (p < 0.05). CONCLUSION: These results indicate that CRP is
      the most important predictor of epoetin hyporesponsiveness.

PMID- 11590898
TI  - Urinary stones following renal transplantation.
AB  - BACKGROUND: The formation of urinary tract stones following renal transplantation
      is a rare complication. The clinical features of stones after transplantation
      differ from those of non-transplant patients. Renal colic or pain is usually
      absent and rarely resembles acute rejection. METHODS: We retrospectively studied
      849 consecutive kidney transplant patients in The Rogosin Institute/The Weill
      Cornell Medical Center, New York who were transplanted between 1980 and 1997 and
      had functioning grafts for more than 3 months, to determine the incidence of
      stone formation, composition, risk factors and patient outcome. RESULTS: At our
      center, urinary stones were diagnosed in 15 patients (1.8%) of 849 functioning
      renal grafts for 3 or more months. Of the 15 patients, 10 were males and 5 were
      females in their third and fourth decade. Eight patients received their
      transplant from living donors and 7 from cadaveric donors. The stones were first
      diagnosed between 3 and 109 months after transplantation (mean 17.8 months) and 5
      patients had recurrent episodes. The stones were located in the bladder in 11
      cases (73.3%), transplanted kidney in 3 cases and in multiple sites in one case.
      The size of stones varied from 3.4 mm to 40 mm (mean 12 mm). The composition of
      stones was a mixed form of calcium oxalate and calcium phosphate in 5 cases and 4
      patients had infected stones consisting of struvite or mixed form of struvite and
      calcium phosphate. Factors predisposing to stone formation included tertiary
      hyperparathyroidism (n = 8), hypercalciuria (n = 5), recurrent urinary tract
      infection (n = 5), hypocitraturia (n = 4), and obstructive uropathy (n = 2). Many
      cases had more than one risk factor. Clinically, painless hematuria was observed
      in 6 patients and dysuria without bacteriuria in 5 patients. None had renal colic
      or severe pain at any time. There were no changes in graft function at diagnosis
      and after removal of stones. Five patients passed stones spontaneously and 8
      patients underwent cystoscopy for stone removal. CONCLUSION: Urinary stone
      formation following kidney transplantation is a rare complication (1.8%).
      Hyperparathyroidism, hypercalciuria, recurrent urinary tract infection and
      hypocitraturia are the most common risk factors, but often there are multiple
      factors which predispose to stone formation. To detect stones and determine their
      location and size, ultrasonography appears to be the most useful diagnostic tool.
      Prompt diagnosis, the removal of stones and stone-preventive measures can prevent
      adverse effects on renal graft outcome.

PMID- 11590900
TI  - A case of Rathke's Cleft Cyst inflammation presenting with diabetes insipidus.
AB  - Rathke's Cleft Cyst (RCC), which is located at the intrasellar region, is
      considered to be the distended remnants of Rathke's pouch, an invagination of the
      stomodeum. Lined with columnar or cuboidal epithelium of ectodermal origin, RCC
      usually contains mucoid material and it is found in 13-22% of normal pituitary
      glands. The cyst rarely leads to the development of symptoms but, when it does,
      the most common presenting symptoms are headache, visual impairment,
      hypopituitarism and hypothalamic dysfunction. However, in some cases it presents
      symptoms of diabetes insipidus, decreased libido and impotence. Recently we
      experienced a case of RCC inflammation presenting with diabetes insipidus and
      treated with transsphenoidal surgery. To our knowledge, this is the first report
      of RCC presenting with symptoms of diabetes insipidus in Korea.

PMID- 11590901
TI  - Restenosis following coronary angioplasty: current status.

PMID- 11590899
TI  - HLA antigens in Malay patients with systemic lupus erythematosus: association
      with clinical and autoantibody expression.
AB  - BACKGROUND: Studies have shown that certain genes within the major
      histocompatibility complex predispose to systemic lupus erythematosus (SLE) and
      may influence clinical and autoantibody expression. Thus, we studied the
      frequency of HLA-DR, -DQA, -DQB and -DPB alleles in ethnic Malays with SLE to
      determine the role of these genes in determining disease susceptibility and their
      association with clinical and immunological manifestations. METHODS: Fifty-six
      Malay SLE patients were enrolled into the study. Demographic, clinical and
      immunological findings were obtained from medical records. HLA-DR, DQ and DP
      typing were done using modified PCR-RELP. Controls were from ethnically-matched
      healthy individuals. RESULTS: We found a strongly significant association of the
      DR2 and DQB1 *0501 and DQB1*0601 (pcorr = 0.03, rr = 3.83, pcorr = 0.0036, rr =
      4.56 and pcorr = 0.0048 and rr = 6.0, respectively). There was also a weak
      increase of DQB1*0.201 and DPB1*0.0901 with a weak decrease of DQA1*0601 and
      DQB1*0503 and *0301 which were not significant after corrections for multiple
      comparisons were made. There was a significant positive association of DR2 and
      DQB1*0501 with renal involvement and DR8 with alopecia. A nonsignificant increase
      of DQB1*0503 in patients with photosensitivity was noted. Significant
      autoantibody associations were also found: DQB1*0601 with anti-Sm/RNP, DR2 with
      antiSSA (Ro)/SSB (La), and DR2, DQB1*0501 and *0601 with antibodies to ds DNA.
      There was no specific DR, DQ or DP associations with age of disease onset (below
      30 years or those at or above 30 years). CONCLUSION: Our data suggests the role
      of the HLA class II genes in conferring SLE susceptibility and in clinical and
      autoantibody expression.

PMID- 11590902
TI  - Hepatopulmonary syndrome in poorly compensated postnecrotic liver cirrhosis by
      hepatitis B virus in Korea.
AB  - BACKGROUND: Hepatopulmonary syndrome (HPS) refers to the association of
      hypoxemia, intrapulmonary shunting and chronic liver disease. But there is no
      clear data about the prevalence of HPS in postnecrotic liver cirrhosis by
      hepatitis B virus (HBV), the most common cause of liver disease in Korea. The aim
      of this study was to investigate the prevalence of HPS in poorly compensated
      postnecrotic liver cirrhosis by HBV, and the correlation of the hepatopulmonary
      syndrome with clinical aspects of postnecrotic liver cirrhosis by HBV. METHODS:
      Thirty-five patients underwent pulmonary function test, arterial blood gas
      analysis and contrast-enhanced echocardiography. All patients were diagnosed as
      HBV-induced Child class C liver cirrhosis and had no evidence of intrinsic
      cardiopulmonary disease. RESULTS: Intrapulmonary shunt was detected in 6/35
      (17.1%) by contrast-enhanced echocardiography. Two of six patients with
      intrahepatic shunts had significant hypoxemia (PaO2 < 70 mmHg) and four showed
      increased alveolar-arterial oxygen gradient over 20 mmHg. Only cyanosis could
      reliably distinguish between shunt positive and negative patients. CONCLUSIONS:
      The prevalence of intrapulmonary shunt in poorly compensated postnecrotic liver
      cirrhosis by HBV was 17.1% and the frequency of hepatopulmonary syndrome was
      relatively low (5.7%). 'Subclinical' hepatopulmonary syndrome
      (echocardiographically positive intrapulmonary shunt but without profound
      hypoxemia) exists in 11.4% of cases with poorly compensated postnecrotic liver
      cirrhosis by HBV. Cyanosis is the only reliable clinical indicator of HPS of HBV
      induced poorly compensated liver cirrhosis. Further studies are required to
      determine if the prevalence and clinical manifestations of HPS varies with
      etiology or with geographical and racial differences.

PMID- 11590903
TI  - The prevalence and awareness of hypertension and the relationship between
      hypertension and snoring in the Korean population.
AB  - BACKGROUND: Hypertension is the most important, and yet modifiable, risk factor
      for cardiovascular diseases. But in many countries, hypertension remains poorly
      controlled. Moreover, sleep apnea syndrome has shown that it is correlated with
      hypertension. The purpose of this study was to investigate the prevalence,
      awareness and control of hypertension among the Korean people and to evaluate the
      relationship between hypertension and snoring. METHODS: A total of 640 subjects
      living in Ansan, a regional city in Korea, were selected randomly, and trained
      nursing students investigated their age, sex, medical history, blood pressure,
      body mass index (BMI) and snoring score. Blood pressures were measured three
      times with a 10-minute interval and then averaged. The degree of snoring was
      estimated using a questionnaire. We divided the subjects into hypertensive (BP >
      or = 140/90 mmHg) versus normotensive group and snorer versus non-snorer group,
      and correlated hypertension with snoring. RESULTS: Of 640 subjects, 311 were
      male. The mean age was 39.7 +/- 14.6 years (18-77 years), the mean BMI (body mass
      index) was 22.4 +/- 3.0 kg/m2. The mean systolic and diastolic blood pressure was
      121 +/- 15.7 mmHg and 79.5 +/- 11.6 mmHg. The prevalence and awareness of
      hypertension were 22.2% and 16.9%, respectively, and the prevalence of snoring
      was 35.2%. With the increment of age, in the male, the prevalence of hypertension
      and snoring were higher, and the snorer group showed a higher risk of
      hypertension than the non-snorer group (Odds ratio 2.32, CI = 1.56-3.39, p =
      0.0001). CONCLUSION: In Korea, the prevalence of hypertension was similar to that
      in the western countries, but the awareness of hypertension was much lower
      compared with western countries. The prevalence of hypertension was higher in the
      snorer group, so more research on the correlation between the two conditions
      should be advanced in the future.

PMID- 11590904
TI  - Restoration of atrial mechanical function after successful radio-frequency
      catheter ablation of atrial flutter.
AB  - BACKGROUND: Atrial mechanical dysfunction and its recovery time course after
      successful radiofrequency ablation of chronic atrial flutter (AFL) has been
      largely unknown. We serially evaluated left atrial function by echocardiography
      after successful ablation of chronic atrial flutter. METHODS: In 13 patients with
      chronic AFL, mitral E wave A wave, and the ratio of A/E velocity were measured at
      1 day, 1 month, 3 months and 6-12 months after successful radiofrequency (RF)
      ablation. Doppler tissue imaging (DTI) technique was also used to avoid load
      dependent variation in the flow velocity pattern. RESULTS: Left atrial mechanical
      function, assessed by A wave velocity and the annular motion, was depressed at 1
      day, but improved significantly at 1 month and maintained through 6-12 months
      after the ablation. Left atrial size did not change significantly. CONCLUSION:
      Left atrial mechanical function was depressed immediately after successful RF
      ablation of chronic AFL, but it improved significantly after 1 month and was
      maintained over one year.

PMID- 11590905
TI  - Survival and prognostic factors in patients with primary pulmonary hypertension.
AB  - OBJECTIVES: Primary pulmonary hypertension (PPH) that affects predominantly young
      and productive people is a progressive fatal disease of unknown cause. The
      objectives of this study were to characterize mortality in patients with PPH and
      to investigate the factors associated with their survival. METHODS: Thirteen
      patients with PPH were enrolled between 1988 and 1996 and followed-up through
      July 1999. Measurements at diagnosis included hemodynamic and pulmonary function
      variables in addition to information on demographic data and medical history.
      RESULTS: 1) The mean age of the patients with PPH enrolled into the study was
      36.1 +/- 9.3 years with female predominance. 2) The estimated median survival was
      3.4 +/- 0.6 years. 3) Decreased cardiac index was the only significant predictor
      of mortality (Cox proportional hazards model). CONCLUSION: Patients with PPH have
      a poor survival expectancy. In this limited study with a small number of
      patients, mortality is largely associated with decreased cardiac index.

PMID- 11590906
TI  - Clinical applications of forced oscillation techniques (FOT) in patients with
      bronchial asthma.
AB  - BACKGROUND: Forced oscillation technique (FOT) is a method to characterize the
      mechanical properties of the respiratory system over a wide range of frequencies.
      Its most important advantage is to require minimal cooperation from the subject.
      This study was performed to evaluate the usefulness of the FOT applications in
      patients with bronchial asthma by estimating the associations between asthma
      severity and FOT parameters, and the relationships between FOT and spirometry
      parameters. METHODS: 216 patients with asthma were enrolled in this study.
      Patients were classified into 3 different groups according to their symptoms and
      pulmonary functions. Respiratory impedance, resistance (at 5 Hz, 20 Hz, 35 Hz)
      and resonant frequency were measured by FOT. FEV1, FVC and MMEF were measured
      with conventional spirometry. RESULTS: There were significant differences of
      resonant frequency, resistance at 5 Hz and 20 Hz, resistance difference at 5 Hz
      and 20 Hz according to asthma severity (p < 0.05, respectively). Resonant
      frequency, resistance at 5 Hz, and impedance were significantly correlated with
      FEV1 (r = -0.55, -0.48, -0.49, p < 0.05, respectively), and with MMEF in patients
      with normal pulmonary function (r = -0.37, -0.35, -0.34, p < 0.05, respectively).
      Resistance at 5 Hz had similar reproducibility compared to FEV1 (resistance at 5
      Hz, r = 0.78 vs FEV1, r = 0.79). CONCLUSION: FOT is a useful and alternative
      method to evaluate the clinical status of bronchial asthma. Further studies will
      be needed to clarify its value for a wide range of clinical applications.

PMID- 11590907
TI  - The effect of cilostazol on glucose tolerance and insulin resistance in a rat
      model of non-insulin dependent diabetes mellitus.
AB  - BACKGROUND: It has been reported that many peripheral vasodilating drugs might
      improve insulin resistance. Cilostazol, a antithrombotic agent, increases
      peripheral blood flow in non-insulin dependent diabetic patients. The effect of
      cilostazol treatment on insulin resistance in streptozotocin (STZ)-induced non
      insulin dependent diabetic Wistar rats was examined. METHODS: About a half of two
      day old neonate siblings were injected intraperitoneally with STZ and maintained
      for six months, at which time they were compared with age-matched control rats
      for intraperitoneal glucose tolerance test (IPGTT) and for glucose infusion rate
      (GINF) in a euglycemic hyperinsulinemic glucose-clamp study. After that, these
      studies were also performed after feeding rat chow containing cilostazol (100
      mg/kg/day) to rats with STZ-induced non-insulin dependent diabetes mellitus for
      four-weeks and compared with those of age-matched control rats. RESULTS: In the
      intraperitoneal glucose tolerance test studies, plasma glucose levels of STZ
      induced non-insulin dependent diabetic rats were significantly higher and plasma
      insulin levels significantly lower than those of age-matched control rats in the
      age of six months. Glucose infusion rate was lower in STZ-induced non-insulin
      dependent diabetic rats than those of age-matched control rats. However, after a
      four-week cilostazol treatment, glucose infusion rate of STZ-induced non-insulin
      dependent diabetic rats was not significantly different from that of control
      rats. CONCLUSION: These findings suggested that cilostazol may improve insulin
      resistance in STZ-induced non-insulin dependent diabetic rats.

PMID- 11590908
TI  - Fra-1 expression in malignant and benign thyroid tumor.
AB  - BACKGROUND: The differential diagnosis of thyroid nodules is very important in
      deciding the treatment modality and the fine needle aspiration is the best
      diagnostic method. But, there are some limitations in use because of inadequate
      test materials and difficulty in interpreting. According to the study of oncogene
      and tumor suppressor gene about the origin of thyroid tumor, expression of Fra-1,
      one of AP-1 complex, is increased in thyroid neoplasm, though not present in the
      normal tissue. So, there is a possibility that it will be used as a method for
      the differential diagnosis of thyroid nodules. We tried to know whether presence
      or absence of Fra-1 expression can be used as a diagnostic method in differential
      diagnosis of thyroid nodules using the immunohistochemical (IHC) staining method.
      METHODS: In 4 types of thyroid tumor that were confirmed by histologic diagnosis
      after operation (18 cases of adenomatous goiter, 16 cases of follicular adenoma,
      30 cases of papillary cancer, 10 cases of follicular cancer), IHC staining method
      was performed to evaluate the expression of Fra-1. RESULTS: In papillary and
      follicular thyroid cancers, the expression of Fra-1 was stronger than in benign
      thyroid tumor, but there was no difference in Fra-1 expression between the two
      types of carcinoma. Weak expression of Fra-1 was observed in all cases of
      follicular adenoma, though it was weaker than in carcinoma, and it was also
      weakly expressed only in some cases (33%) of adenomatous goiter. CONCLUSION: The
      expression of Fra-1 was stronger in thyroid cancer than in benign thyroid tumor,
      but it was impossible to differentiate thyroid cancer from benign thyroid tumor
      by presence or absence of Fra-1 expression using IHC staining method.

PMID- 11590909
TI  - Kidney transplantation in patients with type 1 diabetes mellitus: long-term
      prognosis for patients and grafts.
AB  - Kidney transplantation is the best therapeutic choice to improve survival and
      quality of life in patients with end-stage diabetic nephropathy. Long-term
      prognosis in diabetic patients who received kidney transplants, however, has not
      been delineated. We, therefore, studied patient and graft survival, graft
      function and cause of graft failure in 78 Type I diabetic kidney transplant
      recipients in The Rogosin Institute/The Weill-Cornell Medical Center, New York
      who had functioning grafts for more than one year. The results were compared with
      78 non-diabetic patients who had functioning grafts for more than one year and
      were matched for age, gender, donor source, time of transplantation and
      immunosuppressive therapy protocol. Cumulative patient survival rates for
      diabetic patients were significantly lower than those of non-diabetic patients
      (86% vs. 97% at 5 years and 74% vs. 95% at 10 years, respectively; p < 0.05). The
      most common cause of death was cardiovascular disease. Graft survival rates for
      diabetic patients were also lower than that of non-diabetic patients (71% vs. 80%
      at 5 years and 58% vs. 72% at 10 years, respectively), but the differences did
      not reach statistical significance. Among the 22 failed grafts in diabetic
      patients, 7 (32%) were due to patient death rather than primary graft failure. If
      the patients who died with a functioning graft were censored, graft survival
      rates of diabetic patients approached those of non-diabetic patients (80% vs. 81%
      at 5 years and 65% vs. 73% at 10 years, respectively). Creatinine clearances in
      diabetic patients were lower than that in non-diabetic patients through the
      follow-up period, but the differences were significant only for the first few
      years. At no time was there a higher creatinine clearance for diabetic patients.
      Among the 16 patients who had transplant kidney biopsies two to seven years post
      transplant, 6 showed morphological changes consistent with diabetic nephropathy.
      One patient lost graft function solely by recurrent diabetic nephropathy. We
      conclude that long-term patient survival for diabetic patients is significantly
      lower than that of non-diabetic patients, due primarily to cardiovascular
      disease. Graft survival is comparable between the two groups. Creatinine
      clearances of diabetic patients are lower than those of non-diabetic patients.
      There is no apparent glomerular hyperfiltration at any time in diabetic patients.
      Recurrence of diabetic nephropathy is a rare cause of graft failure in the first
      10 year post-transplant period. Aggressive intervention to modify cardiovascular
      risk factors should improve patient and graft survival in diabetic kidney
      transplant recipients.

PMID- 11590910
TI  - Trematodes of the family Opisthorchiidae: a minireview.
AB  - Examination of the original descriptions of genera placed within the family
      Opisthorchiidae has revealed that only 33 of the original 43 genera are valid
      members of this family. Further study of these descriptions should also reveal
      that many of the subfamilies are also invalid. With reference to the original
      descriptions of these genera, and subsequent literature, a brief survey of the
      family has been compiled. Information on the spectrum of definitive hosts that
      these helminths parasitize is provided, as well as information on the life
      cycles, geographic distribution, and socioeconomic impacts of the family. More in
      depth information is given on those species that are of particular medical
      importance; namely, Clonorchis sinensis, Opisthorchis viverrini, and O. felineus.
      The final aims of this review are to provide information on the entire genera of
      the family Opisthorchiidae, which will aid understanding of the phylogenetic
      relationships not only within the family, but also within the Class Trematoda.

PMID- 11590911
TI  - Epidemiologic characteristics of malaria in non-malarious area, Jeollabuk-do,
      Korea in 2000.
AB  - In South Korea, the north border area has been under vivax malaria epidemic since
      1993. However, Jeollabuk-do, which is about 300 kms from the border, has not
      experienced the same epidemic. I investigated a total of 58 notified cases of
      malaria in Jeollabuk-do in the year 2000. All of the cases had an exposure
      history in the epidemic area. Among them were 49 ex-soldiers, 3 soldiers who
      served near the border area and 6 civilians who traveled there. The causal agent
      of all cases was Plasmodium vivax. Except the civilians, the soldiers and ex
      soldiers were aged in their twenties. In the present study, the incubation period
      was from 6 to 520 days with a median of 157 days, and the latent onset type (92%)
      was more prevalent than the early onset type. Illness onset of most cases (86%)
      peaked during the summer season (June to September) despite of variable
      incubation periods. The time lag for diagnosis ranged from 2 to 42 days with a
      median of 11 days. Jeollabuk-do has not been an area of epidemic until now, but
      incidences have been increasing annually since 1996. In Jeollabuk-do, early
      diagnosis and treatment can be a feasible disease control measure to prevent
      spreading from the epidemic area.

PMID- 11590912
TI  - Experimental induction of the two-host life cycle of Sarcocystis cruzi between
      dogs and Korean native calves.
AB  - Eight dogs were experimentally infected with Sarcocystis by oral inoculation of
      cardiac muscle from naturally infected cattle. The infected dogs commenced
      discharging of sporocysts in the feces after 10 to 12 days of inoculation, and
      continued until 20 and 35 days after inoculation. Three dogs were reinfected with
      cardiac muscle from the naturally infected cattle. Sporocysts reappeared in the
      feces on 12 to 13 days after reinfection. Sarcocystis sporocysts collected from
      the experimentally infected dogs were fed to each of the two 30-day-old Korean
      native calves. The infected calves remained clinically normal, except for the
      high fever (> or = 40 degrees C) and decreased hematocrit values on day 30 to 40
      post inoculation. Muscular cysts of Sarcocystis were found from infected calves
      on day 40 post inoculation. Proliferative forms of Sarcocystis were also observed
      in the muscle of infected calves. These results suggest that the Sarcocystis
      cruzi found in Korean native cattle has a 2-host life cycle with dogs as the
      definitive host and Korean native calves as the intermediate host.

PMID- 11590913
TI  - Effects of specific monoclonal antibodies to dense granular proteins on the
      invasion of Toxoplasma gondii in vitro and in vivo.
AB  - Although some reports have been published on the protective effect of antibodies
      to Toxoplasma gondii surface membrane proteins, few address the inhibitory
      activity of antibodies to dense granular proteins (GRA proteins). Therefore, we
      performed a series of experiments to evaluate the inhibitory effects of
      monoclonal antibodies (mAbs) to GRA proteins (GRA2, 28 kDa; GRA6, 32 kDa) and
      surface membrane protein (SAG1, 30 kDa) on the invasion of T. gondii tachyzoites.
      Passive immunization of mice with one of three mAbs following challenge with a
      lethal dose of tachyzoites significantly increased survival compared with results
      for mice treated with control ascites. The survival times of mice challenged with
      tachyzoites pretreated with anti-GRA6 or anti-SAG1 mAb were significantly
      increased. Mice that received tachyzoites pretreated with both mAb and complement
      had longer survival times than those that received tachyzoites pretreated with
      mAb alone. Invasion of tachyzoites into fibroblasts and macrophages was
      significantly inhibited in the anti-GRA2, anti-GRA6 or anti-SAG1 mAb pretreated
      group. Pretreatment with mAb and complement inhibited invasion of tachyzoites in
      both fibroblasts and macrophages. These results suggest that specific antibodies
      to dense-granule molecules may be useful for controlling infection with T.
      gondii.

PMID- 11590914
TI  - Determination of antigenic domain in GST fused major surface protein (Nc-p43) of
      Neospora caninum.
AB  - The antigenic domain of the major surface protein (Nc-p43) of Neospora caninum
      was examined by polymerase chain reaction of its gene fragments and recombinant
      expression as GST fusion proteins. The fragments of Nc-p43 were as follow: a
      total open reading frame (OFR), T; OFR without signal sequence and C-terminal
      hydrophobic sequence, S; N-terminal 2/3 parts of S, A; C-terminal 2/3 parts, P; N
      terminal 1/3 part, X; middle 1/3 part, Y; and C-terminal 1/3 part, Z,
      respectively. The DNA fragments were cloned into pGEX-4T vector. Recombinant
      plasmids transformed into Escherichia coli of BL21 pLysS (DE3) strain were
      induced to express GST or GST fused fragments of Nc-p43 such as 69 kDa protein
      for T, 66 kDa for S, 52 kDa for A, 53 kDa for P, and 40 kDa proteins for X, Y,
      and Z, respectively in SDS-PAGE. The Nc-p43 fragments of T, S, and P reacted with
      a bovine serum of neosporosis while those of A, X, Y, and Z together with GST did
      not in the western blot. These findings suggest that the antigenic domain of Nc
      p43 of N. caninum may be localized in the C-terminal 2/3 parts. Together with A19
      clone in SAG1 of Toxoplasma gondii (Nam et al., 1996), the P fragment of Nc-p43
      could be used as efficient antigens to diagnose and differentiate those
      infections with both species.

PMID- 11590915
TI  - Austropeplea ollula (Pulmonata: Lymnaeidae): a new molluscan intermediate host of
      a human intestinal fluke, Echinostoma cinetorchis (Trematoda: Echinostomatidae)
      in Korea.
AB  - Three freshwater snail species of the family Lymnaeidae have been reported from
      Korea, Radix auricularia coreana, Austropeplea ollula and Fossaria truncatula.
      Out of 3 lymnaeid snail species, A. ollula was naturally infected with the
      Echinostoma cinetorchis cercariae (infection rate = 0.7%). In the experiments
      with the laboratory-bred snails, F. truncatula as well as A. ollula was also
      susceptible to the E. cinetorchis miracidia with infection rates of 25% and 40%,
      respectively. All of three lymnaeid snail species exposed to the E. cinetorchis
      cercariae were infected with the E. cinetorchis metacercariae. It is evident that
      A. ollula acts as the first molluscan intermediate host of E. cinetorchis in
      Korea, and F. truncatula may be a possible candidate for the first intermediate
      host of this intestinal fluke. Also, three lymnaeid snail species targeted were
      experimentally infected with E. cinetorchis metacercariae.

PMID- 11590916
TI  - Nosocomial submandibular infections with dipterous fly larvae.
AB  - In September 1998, a case of nosocomial cutaneous myiasis caused by Lucilia
      sericata (Meigen, 1826) in a 77-year-old male was found. The patient had been
      receiving partial maxillectomy due to the presence of malignant tumor on
      premaxilla. This is the first verified case involving Lucilia sericata in Taegu,
      Korea. In the present paper, the salient morphological features of the third
      instar larvae involved have been studied.

PMID- 11590917
TI  - Enzyme-linked immunosorbent assay for detection of Trichinella spiralis
      antibodies and the surveillance of selected pig breeding farms in the Republic of
      Korea.
AB  - Trichinellosis is a parasitic zoonosis of public health importance. It is caused
      by Trichinella spiralis which has a wide host range including humans. In the
      present communication, the ELISA technique was employed on a total of 803 blood
      samples from 7 selected pig breeding farms in 1996 for diagnosis and surveillance
      of trichinellosis. Out of the entire 803 samples, nine were found to be suspected
      while one was positive by ELISA. But western blot analyses employed for further
      confirmation have shown that all of 10 samples did not react to larval excretory
      secretory product antigens. These results indicate that pig breeding farms
      included in the present study are free from trichinellosis. However, it does not
      mean Korea is free from trichinellosis since human trichinellosis has recently
      been reported. The necessity of continued surveillance for trichinellosis in both
      pigs and wild animals was discussed.

PMID- 11590918
TI  - Epizootiological survey of hantavirus among rodent species in Ningxia Hui
      Autonomous Province, China.
AB  - Hantaviral antibodies were detected in the sera from Apodemus (A.) agrarius and
      A. peninsulae captured in Ningxia province, China by several different
      serological diagnostic methods. A total of 409 sera from rodent and insectivore
      species were collected in 1999 and examined by indirect immunofluorescent
      antibody assay (IFA). Among them, 19 of 191 (9.9%) sera of A. agrarius and 1 of
      13 (7.7%) sera of A. peninsulae were positive for hantaviral antibodies. The
      other species (Rattus norvegicus, Mus musculus, Cricetulus triton, and Sorex
      cylindricauda) were negative. The reaction pattern of positive serum was
      characterized as scattered and granular virus antigens in the cytoplasm of
      hantavirus infected Vero E6 cells. Some of the A. agrarius sera positive for
      hantavirus were further examined by Western blotting (WB), enzyme-linked
      immunosorbent assay (ELISA), and the focus reduction neutralization test (FRNT).
      By WB, positive sera showed the same specific reaction pattern of baculovirus
      expressed recombinant hantaviral nucleocapsid protein, as shown in hantavirus
      immune serum. By ELISA, IFA-positive sera showed significantly higher optical
      densities (around 1.0) than the negative A. agrarius sera. Hantaan type
      hantavirus was neutralized with the positive sera. These results suggest that A.
      agrarius have hantavirus infection and may play a role as a reservoir animal for
      hantavirus in Ningxia Hui Autonomous Province, China.

PMID- 11590919
TI  - Increased concentrations of protein gene product 9.5 in the synovial fluid from
      horses with osteoarthritis.
AB  - Our previous study established protein gene product 9.5 (PGP 9.5), a ubiquitin C
      terminal hydrolase, as a specific cytochemical marker of synovial lining cells
      (type B synoviocytes) in the horse joint. The present study aimed to detect PGP
      9.5 in the synovial fluid and shows that PGP 9.5 is a valuable marker of
      osteoarthritis in the horse. Immunohistochemical staining confirmed rich and
      consistent localization of PGP 9.5 immunoreactivity in the cytoplasm of synovial
      lining cells in the normal horse joint. Western blot analysis of synovial fluid
      from normal joints could detect a significant band corresponding to that
      contained in the brain and synovial membrane extracts. When 60 synovial fluid
      samples from normal and abnormal joints were assayed with an enzyme-linked
      immunosorbent assay (ELISA) system, the concentration of PGP 9.5 tended to be
      elevated in osteochondrosis dissecance, inflammatory arthropathy and intra
      articular fracture, among which a statistically significant elevation was
      recognizable between the intra-articular fracture and the control. Thus, this
      study demonstrated the possibility that PGP 9.5, derived from synovial lining
      cells, may be a new biochemical marker for arthritic disorders of the horse.

PMID- 11590920
TI  - A survey of canine echinococcosis in Gobi Altai Province of Mongolia by
      coproantigen detection.
AB  - Few studies have been carried out for the prevalence of canine echinococcosis in
      Mongolia. This study was designed to elucidate a preliminary information of the
      prevalence from feces collected in the field. Sixty-seven fecal samples from dogs
      and 2 red foxes in Altai town were collected and examined for Echinococcus
      coproantigen and eggs. Coproantigen detection was performed by a sandwich ELISA
      using a monoclonal antibody EmA9 raised against Echinococcus multilocularis
      somatic antigen. Of the dog samples examined, 17 (25.4%) were positive by the
      ELISA. One out of two foxes was positive, too. Taeniid egg-positive feces were
      recognized in 12 dog feces. Only 6 samples were both coproantigen and egg
      positive. Eggs of Ancylostoma sp., Trichuris sp.; and Capillaria sp.; were also
      registered.

PMID- 11590921
TI  - HIV drug resistance testing: an update for the clinician.

PMID- 11590922
TI  - One size does not fit all.

PMID- 11590923
TI  - Hepatitis C and PIs.
AB  - In a large, retrospective analysis of HIV/HCV-coinfected patients, treatment with
      PI-containing regimens was associated with lower fibrosis scores and a slower
      progression to cirrhosis.

PMID- 11590924
TI  - HIV incidence trends in young women.
AB  - Between 1994 and 1998, the annual number of AIDS cases diagnosed in women
      declined, mirroring similar trends observed in men. During the same time period,
      HIV-infection rates in women also declined. Among women aged 15 to 19, however,
      the number of newly diagnosed HIV infections increased dramatically.

PMID- 11590925
TI  - Comparing different triple-drug combinations.
AB  - Replacing the PI with abacavir in a triple-drug regimen resulted in continued
      plasma viral-load suppression and improvements in lipid abnormalities. In another
      study, PI-containing triple-drug combinations were more likely to reduce viral
      burden in lymphoid tissue than were PI-sparing regimens.

PMID- 11590926
TI  - Pregnancy in a discordant couple.
AB  - An HIV-discordant couple repeatedly failed to conceive through in vitro
      fertilization. Following the death of the HIV-positive father, embryo transfer
      resulted in pregnancy and birth of an HIV-negative child.

PMID- 11590927
TI  - HIV pathogenesis and activation of CD4 cells.
AB  - Selective upregulation of the transcription of nef and tat genes before
      integration into the human genome allows HIV to activate CD4 cells and increase
      viral replication.

PMID- 11590928
TI  - Adding two new drug classes improves outcome in salvage therapy.
AB  - In patients experiencing treatment failure on an NRTI regimen, adding both a PI
      and an NNRTI to salvage therapy resulted in significant virologic improvements
      compared with adding a drug from either class alone.

PMID- 11590929
TI  - Research shows that United States may be due for resurgent HIV epidemic.
AB  - Centers for Disease Control and Prevention officials presented numerous studies
      at the 2nd National HIV Prevention Conference in August showing an upswing in HIV
      risk behaviors among youths, minorities, and men who have sex with men. The
      conference also featured studies showing that many at-risk individuals are being
      tested late for HIV infection. These factors point to a possible increase in AIDS
      cases and deaths soon.

PMID- 11590930
TI  - New studies focus on increased risk behaviors.
AB  - Evidence is mounting that men who have sex with men and other groups at high risk
      for HIV infection are increasingly taking risks through unsafe sexual contacts.
      Seven studies presented at the 2nd National HIV Prevention Conference
      demonstrated significant sexual risks being taken by individuals in eight large
      American cities.

PMID- 11590932
TI  - Rapid HIV tests make comeback.

PMID- 11590931
TI  - Guidelines to help you better detect HIV-positive patients.

PMID- 11590933
TI  - Late detection of HIV key for older nonwhites.
AB  - Evidence that late HIV testing is a major problem, particularly for certain
      groups of HIV-infected people, was bolstered by a recently published study based
      on the HIV Cost and Service Utilization Study. The new study found that older,
      nonwhite people often were first diagnosed with HIV after they already were ill.

PMID- 11590934
TI  - New hope raised for OTC antiviral lubricants.
AB  - After the disastrous findings involving nonoxynol-9 and its use as an antiviral
      vaginal lubrication, clinicians may have been tempted to think there was very
      little possibility of finding a spermicide that could kill HIV. However, the
      possibility of finding a safe and effective antiviral lubricant was given new
      life by a recently published study by researchers at The University of Texas
      Medical Branch at Galveston.

PMID- 11590935
TI  - Routine testing shows benefits in urban hospital. Atlanta effort finds more HIV
      positives.
AB  - Following up on its 1993 recommendations that hospitals and clinics in areas with
      high rates of HIV prevalence offer routine HIV testing to patients, the Centers
      for Disease Control and Prevention conducted a recent study of such a practice.
      From March 20 to Sept. 1, 2000, clinicians in Atlanta were encouraged to
      recommend HIV testing to all urgent-care clinic patients between the ages of 18
      and 65.

PMID- 11590936
TI  - Investigators study role of IL-7 in HIV progression.
AB  - San Francisco investigators have been studying interleukin-7 (IL-7) and its role
      in HIV disease progression in hopes of better understanding how T-cell production
      is regulated and how this knowledge might be applied to therapeutic intervention
      and immunosuppression in either AIDS patients or bone marrow transplant patients.
      This interest has led to the discovery that IL-7 is produced in response to T
      cell depletion, thus facilitating T-cell production--but simultaneously fostering
      HIV-1 disease progression.

PMID- 11590937
TI  - HIV resistance testing benefit is shown.

PMID- 11590938
TI  - What's taking T-20 so long?

PMID- 11590939
TI  - Does HCV negatively impact on HIV disease--progression and survival?

PMID- 11590940
TI  - We need to know more about how HIV drugs work in women.

PMID- 11590941
TI  - The changing outlook for worldwide HIV treatment.

PMID- 11590942
TI  - How to read a scientific paper (1).

PMID- 11590943
TI  - [We shall make a decision].

PMID- 11590944
TI  - [Clinical risk management].

PMID- 11590945
TI  - [The H:S management plan for hospital incidents and risk management].

PMID- 11590946
TI  - [Patient safety. Concepts related to the adverse events].

PMID- 11590947
TI  - [Clinical databases for quality assurance and risk management].

PMID- 11590948
TI  - [Reporting of incidents. Experiences with medical registration systems].
AB  - Current incident reporting systems in Denmark are primarily focused on
      litigation. Epidemiological studies in the United States have shown that only
      2.7% of adverse events that qualify for litigation are identified in such
      systems. Existing Danish reporting on adverse effects and complications is not
      exhaustive and often focused on new medicine/technologies and only a few
      specialties. Published findings on the quality of reporting systems are mostly
      based on local systems, certain specialties, procedures, or products.
      Observational biases are found in both mandatory and voluntary reporting systems.
      Current documentation does not support theories of higher coverage in mandatory
      reporting systems than in voluntary systems. Reporting systems run by authorities
      have shown significantly lower coverage than those run by medical professions.
      Anonymous and confidential systems have higher coverage than open systems. Fast,
      relevant, and constructive feedback to the informants increases the quantity and
      quality of reports. Risk managers and locally based systems could increase
      reporting through better possibilities for direct feedback, although local
      systems have difficulty in initiating major prophylactic actions. Foreign
      epidemiological studies have shown an adverse events incidence of 3-13%. However,
      more than half of the adverse events occur at such a low frequency that it is
      unlikely that isolated hospital systems can produce sufficient information for
      prophylactic action.

PMID- 11590949
TI  - [Joint charts in drug handling. Toward increased drug safety].
AB  - INTRODUCTION: Medication errors contribute to 8% of all hospital admissions.
      Minimalization of the number of information transferrals and improvement in
      communication may increase the quality of drug treatment. MATERIAL AND METHODS:
      The effect of introducing joint charts for prescription and administration on the
      quality of drug handling in a hospital setting is reported. RESULTS: When
      separate charts were used the prescriptions in the case records and the nurses'
      charts for administration did not tally for any of 20 patients. One year after
      introducing the joint charts, prescriptions for the regular medication and
      medication on demand were correct and signed for 88% and 48%, respectively, on a
      patient basis. Ninety-five per cent of the regular administrations were correct
      and signed. Potential interactions were identified in 15% of the prescriptions.
      Discharge medication was stated in 65% of the discharge letters to the family
      doctors. Complete agreement on admission medication between the patient and
      family doctor was found in 39%. DISCUSSION: Joint charts for prescription and
      administration represent a significant step towards safe and rational medical
      treatment. It is more time-consuming. Improvement in communication between all
      parties involved in the treatment of the same patient represents an important
      potential for further improving the quality of care, including drug treatment.

PMID- 11590950
TI  - [Medication problems and risk management].

PMID- 11590951
TI  - [Risk management by reporting critical incidents. Vitamin K and ephedrine mix-up
      at a birthing unit].
AB  - INTRODUCTION: Errors of medication are frequent causes of hazards to patients. It
      has been suggested that containers that look alike constitute a risk of such
      errors. In this article, we present an example of how reporting incidents of
      potential risks, can be applied in their clinical management. MATERIAL AND
      METHODS: As part of a medical technology assessment project on risk management in
      a delivery department, the staff were encouraged to report incidents that could
      create a potential risk to patients. The incidents were assessed by a project
      group as either a general problem to patient safety or a solitary incident. If
      considered a general problem, procedures should be changed and implemented in the
      department. RESULTS: Two incidents were reported, where ephedrine and adrenaline
      were found in a box supposed to contain vitamin K for new-born babies. These were
      considered a general problem by the project group, and the procedure for storing
      and managing ephedrine and adrenaline in the delivery department was changed to
      prevent new cases. DISCUSSION: Near misses occur more often than actual errors,
      and we argue that, as they are easier to discover, it is important to learn from
      them and thus prevent further incidents. A forum should be set up to exchange
      experiences of acknowledged risks, hazards, analytical results and preventive
      solutions.

PMID- 11590952
TI  - [Analysis of primary causes of incidents in a department of radiotherapy,
      Rigshospitalet].

PMID- 11590953
TI  - [Incidence of adverse events in hospitals. A retrospective study of medical
      records].
AB  - INTRODUCTION: Over the past decade a number of studies on the incidence and
      preventability of adverse events in the health care have been published in the
      US, Australia and the UK. So far no similar study has been performed in Denmark.
      In order to determine whether foreign findings could be generalised to Danish
      health care, a pilot study on adverse events was carried out in Danish acute care
      hospitals. METHOD: Chart reviews were carried out on 1.097 acute care hospital
      admissions, sampled from the central Danish National Patient Register. The sample
      was truly proportional with no over-sampling of high-risks groups. Chart reviews
      was done in 17 different acute care hospitals, reviewing between 20 and 204
      admissions per hospital. Adverse events was identified using a three-step
      procedure: 1) Nurse screening by 18 criteria identifying high-risk groups. 2)
      Independent reviews by pairs of consultants. 3) In case of disagreement between
      second step consultants, two additional independent reviews was performed by new
      consultants (internist and surgeon) followed by conference. All chart reviews
      were performed independent of medical specialty. All nurses and doctors were
      senior and experienced clinicians. RESULTS: In 114 admissions 176 Adverse Events
      (AEs) were identified. The prevalence of admissions with adverse events were 9.0%
      of all admissions. Preventability of adverse events was found in 46 of admissions
      (40.4% of AEs). The adverse events caused on average a 7.0 days prolonged
      hospital stay. Most adverse events resulted in minor, transient disabilities.
      Permanent disability or death in relation to adverse event were recorded in 30
      admissions. DISCUSSION: The findings from the Danish Adverse Event Study are
      similar to the results found in Australia, United Kingdom and the United States.
      It is therefore recommended that further Danish research, is directed towards
      high-risk groups focussing on narratives and intervention and towards research in
      primary health care.

PMID- 11590954
TI  - [Munchausen syndrome--a risk to patient and caregiver].
AB  - Munchausen's syndrome is a rare disorder, characterised by a disturbance in the
      person's character and behaviour, which consists of mental elaboration of somatic
      symptoms and simulation of illness, where the patient himself produces the
      symptoms. This case history highlights certain risks when the Munchausen patient
      comes into contact with the health service.

PMID- 11590955
TI  - [Picture of the month: tracheo-bronchopathia osteoplastica].

PMID- 11590956
TI  - [Fabry disease--a special therapy now available].

PMID- 11590957
TI  - [Legionella in Odense--what really happened].

PMID- 11590958
TI  - [The dangerous sunbeam].

PMID- 11590959
TI  - [The concept of anxiety, a therapeutic model and its implication].

PMID- 11590961
TI  - [Three-months infantile colic].

PMID- 11590960
TI  - [Estrogen supplementation can cause migraine].

PMID- 11590962
TI  - [Blood donors and vCJD].

PMID- 11590963
TI  - Norepinephrine and selective norepinephrine reuptake inhibitors in depression and
      mood disorders: their pivotal roles.

PMID- 11590964
TI  - Stress, norepinephrine and depression.
AB  - Stress is an important precipitant factor in depression, and the changes in
      various body systems that occur in depression are similar to those observed in
      response to stress. This paper discusses the interactions among the immune,
      endocrine and norepinephrine systems that are evident in patients with
      depression, as well as those affected by stress. Many of the stress-induced
      changes can be reversed by antidepressants, particularly norepinephrine reuptake
      inhibitors.

PMID- 11590965
TI  - Postreceptor pathways for signal transduction in depression and bipolar disorder.
AB  - Study of the norepinephrine pathway has elucidated the pathophysiology of
      depression and bipolar disorder. Various elements along this pathway, including
      adrenoreceptors, G proteins, cyclic adenosine monophosphate (AMP), cyclic AMP
      regulatory element binding protein and brain-derived neurotrophic factor, have
      been identified as potential targets for antidepressants and mood-stabilizing
      drugs. The results of a wide range of research in this area, along with the
      hypotheses now under investigation, are summarized in this paper.

PMID- 11590966
TI  - Quality of life: an important dimension in assessing the treatment of depression?
AB  - Quality of life is used to assess the overall impact of medical treatments from
      the patient's perspective. Because depression affects a person's ability to
      function at work and at home, the evaluation of various treatments must include
      an assessment of patients' physical, social and psychological status. This paper
      classifies and evaluates a variety of widely used health-related quality-of-life
      questionnaires that have potential value as outcome measures in the treatment of
      depression. The paper also outlines how these measures have been beneficial in
      the assessment of depressed patients. They reveal differences between patients
      with depression and control groups, are sensitive to change in status during
      treatment, have predictive value for outcome measures and provide additional
      information about timelines for improvement in psychosocial functioning, which
      may occur at a different rate than changes in other depressive symptoms. Despite
      the limitations of these questionnaires, they provide an important additional
      dimension to the evaluation of treatment with antidepressant medications.

PMID- 11590967
TI  - Crosstalk between the norepinephrine and serotonin systems and its role in the
      antidepressant response.
AB  - Many behavioural overlaps exist in the effects of norepinephrine (NE), serotonin
      (5-HT) and dopamine, and it is now thought that complex behaviour patterns may
      reflect interactions among these neurotransmitters. There is a wide variety of
      evidence for the pivotal role of the NE system in the pathogenesis and treatment
      of major depression. This paper discusses the functioning of the NE system,
      specifically the regulation of neuronal firing and the postsynaptic responses to
      NE, which can be controlled by norepinephrine reuptake inhibitors and other
      drugs. In addition, interactions between NE neurons and 5-HT neurons have
      implications for the treatment of depression and anxiety disorders. Specifically,
      the projections of 5-HT neurons have an inhibitory effect on NE neurons, which
      means that selective serotonin reuptake inhibitors also affect the NE system.
      Further experiments and long-term studies will increase knowledge of the
      mechanisms of action of various psychopharmacologic agents and may eventually
      lead to better therapeutic choices.

PMID- 11590968
TI  - Beyond the human genome.

PMID- 11590969
TI  - Labelled alpha-methyl-L-tryptophan as a tracer for the study of the brain
      serotonergic system.
AB  - The alpha-methyl-L-trypotophan (alpha-MTrp) method for the study of the brain
      serotonergic system is based on the fact that labelled alpha-MTrp is taken up by
      and, in part, retained in the brain, and this retention (trapping) is
      proportional to brain serotonin (5-HT) synthesis. A 3-compartment model is
      proposed in which the plasma, the precursor and irreversible pools are
      mathematically distinct compartments. The irreversible compartment is assumed to
      be the one in which the tracer is trapped. By definition, the tracer from the
      irreversible compartment does not exchange directly with the plasma compartment.
      The rate at which labelled alpha-MTrp is trapped is converted to the rate of 5-HT
      synthesis by dividing it by a conversion factor, called the lumped constant, and
      multiplying it by the plasma-free tryptophan concentration. Our results revealed
      that brain 5-HT synthesis can be influenced by the extraneuronal concentration of
      5-HT and that, generally, the influence is not uniform throughout the brain. They
      also suggest that brain trapping of labelled alpha-MTrp relates to 5-HT
      synthesis. The proposed procedure for converting the rate at which labelled alpha
      MTrp is trapped to brain 5-HT synthesis rates is based on measurements that
      suggest that plasma-free Trp relates to brain 5-HT synthesis. However, as with
      all biological models, there is likely room for improvement in our approach.

PMID- 11590971
TI  - What do patients in a lithium outpatient clinic know about lithium therapy?
AB  - OBJECTIVE: To determine how much patients know about lithium therapy and to
      examine factors that might influence this knowledge. SETTING: Lithium outpatient
      clinic. PATIENTS: Patients (n = 123) affiliated with a lithium outpatient clinic
      (mean treatment duration of 12 years). Diagnoses, according to the Diagnostic and
      Statistical Manual of Mental Disorders, 3rd edition, revised, included bipolar
      disorder, recurrent unipolar depression and schizoaffective disorder. OUTCOME
      MEASURES: Quantitative assessment of lithium-related knowledge, obtained by
      responses to a questionnaire adapted from the Lithium Knowledge Test, and factors
      affecting this knowledge. RESULTS: Age was negatively correlated with lithium
      therapy knowledge scores, whereas duration of treatment, sex, education and
      diagnosis appeared to be unrelated to knowledge. CONCLUSION: Patient education
      about lithium treatment should be intensified, especially for older patients
      taking lithium because adverse drug reactions pose a greater risk to the elderly.

PMID- 11590970
TI  - Influence of the endogenous opioid system on high alcohol consumption and genetic
      predisposition to alcoholism.
AB  - There is increasing evidence supporting a link between the endogenous opioid
      system and excessive alcohol consumption. Acute or light alcohol consumption
      stimulates the release of opioid peptides in brain regions that are associated
      with reward and reinforcement and that mediate, at least in part, the reinforcing
      effects of ethanol. However, chronic heavy alcohol consumption induces a central
      opioid deficiency, which may be perceived as opioid withdrawal and may promote
      alcohol consumption through the mechanisms of negative reinforcement. The role of
      genetic factors in alcohol dependency is well recognized, and there is evidence
      that the activity of the endogenous opioid system under basal conditions and in
      response to ethanol may play a role in determining an individual's predisposition
      to alcoholism. The effectiveness of opioid receptor antagonists in decreasing
      alcohol consumption in people with an alcohol dependency and in animal models
      lends further support to the view that the opioid system may regulate, either
      directly or through interactions with other neurotransmitters, alcohol
      consumption. A better understanding of the complex interactions between ethanol,
      the endogenous opioids and other neurotransmitter systems will help to delineate
      the neurochemical mechanisms leading to alcoholism and may lead to the
      development of novel treatments.

PMID- 11590972
TI  - Use of the Medication Event Monitoring System to estimate medication compliance
      in patients with schizophrenia.
AB  - OBJECTIVE: To determine the feasibility of using the Medication Event Monitoring
      System (MEMS) to estimate medication compliance in patients with schizophrenia or
      schizoaffective disorder. SUBJECTS AND SETTING: Fourteen of 35 consecutive
      patients admitted to a psychiatric inpatient hospital with schizophrenia or
      schizoaffective disorder who met eligibility requirements and gave informed
      consent. INTERVENTION: After random assignment to either risperidone or typical
      antipsychotic treatment, medication upon discharge from hospital was dispensed in
      a bottle with a MEMS cap which recorded the number of bottle openings and the
      date and time of each opening. The first 6 patients were asked to return monthly
      for data downloading. The next 8 were asked to return weekly during the first
      month and every 2 weeks thereafter; they were also paid $5 for returning each
      bottle. OUTCOME MEASURES: MEMS data collected over a 6-month period and hospital
      readmission data. RESULTS: Patient medication compliance data were collected from
      10 (71%) of 14 patients during the first month, from 7 (58%) of 12 (2 patients
      dropped out) during the second and from 5 (45%) of 11 (a third patient dropped
      out) during months 3-6. Mean compliance rates were 63% for the first month and
      ranged from 56% to 45% over the next 5. First-month compliance rates were
      significantly lower for those who were subsequently readmitted to hospital (n =
      7) than for those who were not (p < 0.01). CONCLUSIONS: Electronic monitoring
      devices can be used to estimate compliance with medication regimens in patients
      with severe schizophrenic disorders, but there are methodological improvements
      that can be made to increase data recovery and compliance, and these are
      discussed.

PMID- 11590973
TI  - Accuracy of the Pepin method to determine appropriate lithium dosages in healthy
      volunteers.
AB  - OBJECTIVE: To assess if the lithium dosage prescribed according to the Pepin
      method leads to therapeutic serum concentrations of lithium. METHODS: For 13
      healthy volunteers, the initial daily doses of lithium were calculated according
      to the Pepin formula with a view to obtaining a serum lithium level of 0.8
      mmol/L. Lithium was administered twice daily for 21 days, and blood samples were
      drawn daily, 12 hours after the last dose was taken. Dosage was adjusted if serum
      concentrations were below 0.6 mmol/L or above 1.0 mmol/L or if major side effects
      were reported. RESULTS: Daily lithium doses ranged from 1050 mg to 1950 mg (mean
      1569 mg, standard deviation [SD] 291 mg), The mean serum lithium concentrations
      for weeks 1, 2 and 3 were 0.74 mmol/L (SD 0.19 mmol/L), 0.67 mmol/L (SD 0.22
      mmol/L) and 0.69 mmol/L (SD 0.13 mmol/L), respectively. Within-subject variance
      was negligible. Sixty-eight percent of the serum lithium concentration
      measurements fell between 0.57 mmol/L and 0.83 mmol/L, and 84% fell within the
      recommended therapeutic range of 0.60 mmol/L and 1.20 mmol/L. CONCLUSIONS: The
      Pepin method is a safe but conservative method for predicting the appropriate
      daily dose of lithium.

PMID- 11590975
TI  - Violent acts associated with fluvoxamine treatment.

PMID- 11590974
TI  - Early response to light therapy partially predicts long-term antidepressant
      effects in patients with seasonal affective disorder.
AB  - OBJECTIVE: To determine if the antidepressant effect of 1 hour of light therapy
      is predictive of the response after 1 and 2 weeks of treatment in patients with
      seasonal affective disorder (SAD). PATIENTS: Twelve patients with SAD. SETTING:
      National Institutes of Health Clinical Center, Bethesda, Md. INTERVENTIONS: Light
      therapy for 2 weeks. OUTCOME MEASURES: Scores on the Seasonal Affective Disorder
      Version of the Hamilton Depression Rating Scale (SIGH-SAD) on 4 occasions (before
      and after 1 hour of light therapy and after 1 and 2 weeks of therapy) in the
      winter when the patients were depressed. Change on typical and atypical
      depressive scores at these time points were compared. RESULTS: Improvement of
      atypical depressive symptoms after 1 hour of light therapy positively correlated
      with improvement after 2 weeks of therapy. CONCLUSION: In patients with SAD, the
      early response to light therapy may predict some aspects of long-term response to
      light therapy, but these results should be treated with caution until replicated.

PMID- 11590976
TI  - Long-term treatment with clozapine in an adult with autistic disorder accompanied
      by aggressive behaviour.

PMID- 11590977
TI  - Switching to nevirapine--results after one year.

PMID- 11590978
TI  - Effect of HAART on cervical growths.

PMID- 11590979
TI  - Immune booster used to fight drug-resistant herpes.

PMID- 11590980
TI  - Sexual dysfunction and HAART.

PMID- 11590981
TI  - Lipid-lowering drugs and changes to diet can make a difference.

PMID- 11590982
TI  - Depression linked to immune system decline in women.

PMID- 11590983
TI  - Is college dangerous?

PMID- 11590984
TI  - Outbreaks of acute gastroenteritis associated with Norwalk-like viruses in campus
      settings.
AB  - Norwalk-like viruses (NLVs) are transmitted by fecally contaminated food, water,
      fomites, and person-to-person contact. They are a leading cause of acute
      gastroenteritis epidemics in industrialized countries. NLV outbreaks are
      characterized by a 12- to 48-hour incubation period; nausea, vomiting, and
      diarrhea for 24 to 72 hours; and high secondary attack rates. NLV infections
      spread rapidly on college and university campuses because of close living
      quarters, shared bathrooms and common rooms, many food handlers, popular self
      service salad bars in dining halls, and person-to-person contact through sports
      and recreational activities. The illness is generally mild and self-limited but
      an outbreak can strain the resources of campus health services and cause high
      absenteeism among both students and staff. Treatment is primarily through
      antiemetic medication and oral rehydration. Prevention and control of NLV
      outbreaks rests on promoting hand washing; enforcement of strict hygiene in all
      food preparation areas; and prompt, rigorous cleaning of potentially contaminated
      areas where someone has been ill.

PMID- 11590985
TI  - The prevalence of elevated psychological distress among Canadian undergraduates:
      findings from the 1998 Canadian Campus Survey.
AB  - For a study of elevated psychological distress, the authors used data based on a
      national probability sample of 7,800 Canadian undergraduate students from 16
      universities. They used the 12-item General Health Questionnaire to assess mental
      health. Thirty percent of the students in the sample reported elevated
      psychological distress, which varied significantly according to sex, region, year
      of study, and recreational and academic orientation. Rates of elevated distress
      were significantly higher among the students than among the general population in
      Canada.

PMID- 11590986
TI  - Stress, negative social exchange, and health symptoms in university students.
AB  - Although social support has been studied extensively in terms of its role in the
      relationship between stress and health, less attention has been devoted to the
      impact of negative social interactions. In this investigation, the authors
      examined the unique contributions of positive social support and negative social
      exchange in the relationship between stress and health symptoms, using data from
      206 undergraduates at a large state university. Negative social exchange
      accounted for more variance in physical health symptoms than did life-event
      stress, daily hassles, or social support. The relationship between negative
      social interaction and physical symptoms was not the result of variance shared
      with psychological well-being. The importance of attending to negative aspects of
      social interaction among university students in terms of their health and well
      being is discussed.

PMID- 11590987
TI  - The effects of eliminating alcohol in a college stadium: the Folsom Field beer
      ban.
AB  - In fall 1996, the University of Colorado at Boulder instituted a ban on beer
      sales at football games. To evaluate the effects of the ban, the authors
      collected two types of data: first, they examined the effects of the ban on game
      day security incidents; second, they looked at survey data from season ticket
      holders and students. They administered the surveys after the first two postban
      seasons to assess ticket holders' attitudes about the new policy. The incident
      data they found indicated dramatic decreases in arrests, assaults, ejections from
      the stadium, and student referrals to the judicial affairs office following the
      ban. Survey data also indicated moderately negative attitudes about the ban among
      students and some season ticket holders. However, all fans were likely to renew
      their tickets regardless of their attitudes toward the policy. The study
      illustrates what can be achieved when alcohol is eliminated from a setting that
      frequently fosters disorderly and aggressive behaviors.

PMID- 11590988
TI  - Attitudes toward lesbian, gay, and bisexual college students: the contribution of
      pluralistic ignorance, dynamic social impact, and contact theories.
AB  - Social psychology theories may be useful in developing new interventions to
      reduce prejudice against lesbian, gay, and bisexual (LGB) college students. For
      this preliminary study, the authors surveyed 109 college dormitory residents to
      determine their personal comfort with LGB students and their perceptions of other
      students' comfort with these individuals. They found widespread evidence of
      pluralistic ignorance--the students rated themselves as significantly less anti
      gay than either their friends or the typical student. Students' attitudes showed
      geographic clustering, with the building of residence a significant predictor of
      students' attitudes. Finally, consistent with the contact hypothesis, the
      perception that 1 or 2 LGB students lived on the same floor or in the same
      building was associated with more positive attitudes.

PMID- 11590989
TI  - Normal endothelial function after meals rich in olive or safflower oil previously
      used for deep frying.
AB  - BACKGROUND AND AIM: Polyunsaturated fats are more susceptible to oxidation during
      heating than monounsaturated fats but their effects on endothelial function when
      heated are unknown. The aim of this study was to compare the effect of meals rich
      in heat-modified safflower and olive oils on postprandial flow-mediated
      endothelium-dependent dilation (EDD) in healthy men. METHODS AND RESULTS: Flow
      mediated EDD and glyceryltrinitrate-induced endothelium-independent dilation of
      the brachial artery were investigated in 14 subjects before and 4 hours after
      meals rich in olive oil and safflower oil used hourly for deep-frying for 8 hours
      in a double-blind crossover study design. There were high levels of lipid
      oxidation products (peroxides and carbonyls) in both heated oils. Plasma
      triglycerides were markedly increased at 4 hours after heated olive oil (1.26 +/-
      0.43 vs 2.06 +/- 0.97 mmol/L) and heated safflower oil (1.44 +/- 0.63 vs 1.99 +/-
      0.88 mmol/L). There was no change in EDD between fasting and postprandial studies
      and the response during the postprandial period was not significantly (p = 0.51)
      different between the meals (heated olive oil: 4.9 +/- 2.2% vs 4.9 +/- 2.5%;
      heated safflower oil: 5.1 +/- 3.1% vs 5.6 +/- 3.4%). CONCLUSIONS: Meals rich in
      olive and safflower oils previously used for deep frying and containing high
      levels of lipid oxidation products increase postprandial serum triglycerides
      without affecting endothelial function. These findings suggest that relatively
      short-term use of these vegetable oils for frying may not adversely affect
      postprandial endothelial function when foods containing the heat-modified oils
      are consumed.

PMID- 11590990
TI  - Changes in lipoprotein(a) levels and hormonal correlations during a weight
      reduction program.
AB  - BACKGROUND AND AIM: To examine the effects of a weight reduction program on serum
      lipoprotein(a) [Lp(a)] levels and investigate whether the hormonal modifications
      occurring during weight loss may explain the changes in Lp(a) levels. METHODS AND
      RESULTS: This longitudinal clinical intervention study of a low-calorie diet
      involved 62 healthy obese patients (21 men aged 32 +/- 9.6 years and 41 women
      aged 37 +/- 14.6 years). Their anthropometric parameters (weight, height, body
      mass index, waist-to-hip ratio), fasting serum lipid levels, hormones (total
      testosterone, estradiol, total triiodothyronine, insulin), sex hormone binding
      globulin (SHBG) and blood sugar levels were determined at baseline and after six
      weeks of dietary treatment. A 7.5% loss in initial body weight was achieved and
      there was a statistically significant decrease in serum total cholesterol, LDL
      cholesterol, HDL-cholesterol and triglycerides (p < 0.001). No changes in Lp(a)
      levels were observed in the study population as a whole, but there was a 17.6% (p
      < 0.05) reduction in the subjects with high pre-treatment Lp(a) values (> 20
      mg/dL). The decrease in Lp(a) levels closely correlated with initial Lp(a) levels
      (r = 0.81 p < 0.001), but did not correlate with changes in anthropometric
      parameters or the hormonal modifications occurring during the weight loss.
      CONCLUSIONS: A low-calorie diet associated with weight loss in obese subjects may
      have beneficial effects on serum Lp(a) levels in patients with high pre-treatment
      Lp(a) concentrations. This effect seems to be independent of the hormonal changes
      observed during weight loss.

PMID- 11590991
TI  - Diet enrichment with calcium and magnesium enhances the cholesterol-lowering
      effect of plant sterols in obese Zucker rats.
AB  - BACKGROUND AND AIM: Recent clinical studies have demonstrated that plant sterols
      moderately lower serum cholesterol levels in patients with mild
      hypercholesterolemia. Furthermore, there is evidence suggesting that mineral
      nutrients, such as calcium and magnesium, may also decrease serum cholesterol
      concentrations. In this study, we tested the hypothesis that supplementation with
      mineral nutrients may enhance the cholesterol-lowering effect of plant sterols in
      obese Zucker rats. Furthermore, we compared the lipid-lowering effects of
      monovalent sodium and potassium cations with those of divalent calcium and
      magnesium cations. METHODS AND RESULTS: A Western-type high-fat/high-cholesterol
      diet increased serum cholesterol by 175% and liver cholesterol by 65% in
      comparison with a low-fat/low-cholesterol control diet. On the contrary, the high
      fat/high-cholesterol diet decreased intestinal cholesterol absorption, as
      assessed by means of serum campesterol-, sitosterol-, and sitostanol-to
      cholesterol ratios, thus indicating that it was under negative feedback
      regulation. Supplementation of the high-fat/high-cholesterol diet with plant
      sterols or mineral nutrients partially prevented the diet-induced increased in
      serum cholesterol and, when given concurrently, their cholesterol-lowering effect
      was enhanced. Their combination also effectively prevented the diet-induced
      increase in liver cholesterol concentration, and had beneficial effects on liver
      and myocardial hypertrophy, and the development of obesity. These beneficial
      effects were at least partially mediated by an enhanced blockade of intestinal
      cholesterol absorption. Interestingly, only divalent cations enhanced the
      cholesterol-lowering effect of plant sterols, thus supporting the idea that the
      lipid-lowering effect of divalent cations is related to the formation of
      insoluble and inabsorbable calcium and magnesium chelates with fatty acids.
      CONCLUSIONS: Our findings indicate that the cholesterol-lowering effect of plant
      sterols is enhanced by the co-administration of divalent calcium and magnesium
      cations but not by monovalent sodium and potassium cations.

PMID- 11590992
TI  - Preprandial combination of lispro and NPH insulin improves overall blood glucose
      control in type 1 diabetic patients: a multicenter randomized crossover trial.
AB  - BACKGROUND AND AIM: While lispro insulin has been reported to lower postprandial
      blood glucose concentrations, less consistent effects have been shown for
      glycosylated hemoglobin (HbA1c) levels. Aim of this study was to determine
      whether pre-meal association of NPH, an intermediate-acting insulin, with lispro
      improves overall glycemic control in type 1 diabetic patients. METHODS AND
      RESULTS: Eighty-five type 1 diabetic patients were studied in a multicenter
      randomized comparative (human regular vs lispro insulin) crossover (3-month)
      study in which NPH insulin was given as a dinner or bedtime injection and at
      breakfast and lunch if necessary. The number of injections was kept constant: 42%
      and 58% of patients injected insulin 3 and 4 times per day, respectively. Fasting
      and preprandial blood glucose levels were similar, while postprandial levels
      improved after lispro compared to human regular insulin (breakfast: 8.28 +/- 2.39
      vs 9.28 +/- 2.72 mmol/l; lunch: 8.33 +/- 2.67 vs 9.06 +/- 2.67 mmol/l, dinner:
      8.06 +/- 2.72 vs 9.28 +/- 2.44 mmol/l, ANOVA: p = 0.003). HbA1c also improved
      after lispro: 8.1 +/- 0.9 vs 8.3 +/- 0.8%, p < 0.05. The rate of hypoglycemia was
      similar. Patients showed better acceptance of lispro treatment (p < 0.001).
      CONCLUSIONS: Lispro improves overall blood glucose control in type 1 diabetic
      patients without increasing the incidence of hypoglycemia. This can be achieved
      by an optimal combination of lispro insulin with NPH whenever the time intervals
      between meals are too long.

PMID- 11590993
TI  - Effect of wine ethanol on serum iron and ferritin levels in patients with
      coronary heart disease.
AB  - BACKGROUND AND AIM: The association between high body iron stores and coronary
      heart disease (CHD) is a subject of intense debate whereas wine consumption is
      known to be associated with a low CHD rate. It has been suggested that the
      inhibition of iron absorption is one of the possible mechanisms of the CHD
      protective effects of drinking. METHODS AND RESULTS: We analysed the
      interrelationships of wine ethanol intake and fasting serum ferritin, iron and
      gamma glutamyl transferase (GGT) in patients enrolled in the Lyon Diet Heart
      Study, a secondary prevention trial designed to test whether a Mediterranean-type
      diet may protect against CHD. The intake of wine ethanol was evaluated in the 24
      hours preceding blood sampling, and expressed as a percentage of the total daily
      energy intake. Data were obtained from 437 consecutive patients. There was a
      positive relationship (Spearman statistics) between wine ethanol and the serum
      levels of iron (r = 0.21, p < 0.0001), ferritin (r = 0.23, p < 0.0001) and GGT (r
      = 0.31, p < 0.0001). Uni- and multilinear regression analyses after excluding non
      drinkers and log transforming the variables yielded similar results. CONCLUSIONS:
      The available data showing positive relationships between wine ethanol intake and
      serum concentrations of both ferritin and iron in patients with CHD tend to
      disprove the hypothesis that wine ethanol consumption could decrease iron stores
      and thereby the risk of CHD. Further studies are required to investigate the
      mechanism(s) by which wine drinking reduces the risk of CHD.

PMID- 11590994
TI  - Who's afraid of n-6 polyunsaturated fatty acids? Methodological considerations
      for assessing whether they are harmful.
AB  - N-6 fatty acids are essential for normal growth, development and health, and so
      extreme care is necessary before deciding that they are harmful. Theoretical and
      epidemiological evidence suggests the involvement of n-6 polyunsaturated fatty
      acids (PUFAs) in disease progression or prevention; however, n-6 function cannot
      be considered in isolation but needs to be seen as part of the complex of
      nutrient interactions with n-3 fatty acids (which compete for the same enzymatic
      pathways) and antioxidants. Insulin sensitivity might be the common factor
      relating disease to fatty acid metabolism both within and between the fatty acid
      pathways. High linoleate to arachidonate concentrations have been observed in
      insulin resistance, diabetic complications and some tumours, but these are
      multifactorial processes that include many lifestyle determinants and it is
      therefore wrong to condemn only n-6 fatty acids in their etiology. The results
      based on the criteria for assessing diet and disease are still insufficient to
      declare n-6 fatty acids a serious health risk; at most, the verdict should be
      "not proven". The question may never be conclusively answered not only because
      prospective dietary intervention trials (unlike those with n-3 fish oil capsules)
      are fraught with dosage and compliance problems, but also because of high
      background linoleate consumption. Tissue fatty acid composition may be a suitable
      biomarker for PUFA intake but there are many theoretical and methodological
      problems concerning other suitable markers because of the multiplicity of their
      biological effects. Before making evidence-based dietary recommendations, future
      research should consider: 1) how n-3 and n-6 dietary PUFAs affect the
      physiological balance (dose-response) of their derivatives such as eicosanoids
      and the newly-discovered fatty acid amides; 2) the metabolic interactions between
      n-6 and n-3 fatty acid pathways (including gene-nutrient effects); 3) the need
      for antioxidant cover (quantity and quality); 4) prospective intervention trials.

PMID- 11590995
TI  - The role of PPAR alpha in obesity.
AB  - Obesity is a rapidly increasing health problem in all developed countries.
      Overweight rarely occurs in isolation but as part of a complex pattern of
      metabolic abnormalities ("metabolic syndrome" or "syndrome X") consisting of
      hyperlipidemia, hypoalphalipoproteinemia, type II diabetes and atherosclerosis.
      The disorder is considerably influenced by genetic, behavioural and nutritional
      factors. Recent data indicate that a group of closely related nuclear receptors,
      the peroxisome proliferator-activated receptors (PPARs), may be involved in the
      metabolic changes ultimately leading to obesity. This review summarises the
      latest developments in the PPAR field, with particular emphasis being placed on
      the physiological function of PPAR alpha during various nutritional states, and
      the possible role of PPAR alpha in obesity.

PMID- 11590996
TI  - Visceral obesity and the metabolic syndrome: effects of weight loss.
AB  - A large body of experimental and epidemiological evidence has established an
      association between visceral obesity and the metabolic syndrome, which retains
      its power throughout the spectrum of adiposity and is still clinically meaningful
      in severe obesity. The association may be due to an overload of liver free fatty
      acids (FFA) produced by the high lipolytic activity of omental fat. A substantial
      improvement in all aspects of the metabolic syndrome with only a moderate degree
      of weight loss has been observed in a large number of randomised controlled
      studies and can also be obtained in severe obesity, despite the fact that the
      patients remain obese. The reasons for this apparent dissociation between weight
      loss and metabolic improvement are not yet clearly understood, but may involve
      the relationship between visceral fat and metabolic alterations. The results of
      some studies suggest that the favourable metabolic changes observed in obese
      patients with weight loss may be directly attributable to a reduction in visceral
      fat, and other studies have recently shown that a rapid and preferential
      reduction in visceral fat mass occurs during the first phase of weight loss in
      morbidly obese patients possibly as a result of sympathetic nervous system
      activation. It is therefore possible that the apparent dissociation between
      weight loss and metabolic improvement is partially due to a difference in the
      responsiveness of visceral and subcutaneous adipose tissue to energy restriction:
      i.e. the fact that the metabolic profile of patients with visceral obesity may
      substantially improve after the loss of only a few kilograms of body weight could
      be related to a greater relative reduction in the amount of visceral rather than
      other fat. In this respect, the characteristically high rate of visceral fat
      mobilisation can also be seen as a good target for interventions aimed at
      reducing cardiovascular risk factors.

PMID- 11590997
TI  - How to handle individual patients with or at risk for coronary heart disease.
      Coronary heart disease--still a threat.

PMID- 11590999
TI  - Terrorist attacks alter public mood, shift priorities for federal funding.

PMID- 11590998
TI  - Absence of the R3531C mutation in the apoB gene in Czech hypercholesterolaemic
      patients.

PMID- 11591000
TI  - Conference. Miami Beach sessions cancelled: materials might be posted online.

PMID- 11591001
TI  - GBV-C and HIV.

PMID- 11591002
TI  - Antiretroviral doses.

PMID- 11591003
TI  - Risks of WSW.

PMID- 11591004
TI  - Stem-cell breakthrough may advance HIV/AIDS treatments.

PMID- 11591005
TI  - Southern women apparently face higher HIV infection rates.

PMID- 11591006
TI  - Conference examines need for more study of AIDS stigma.

PMID- 11591007
TI  - Stigma, bias present barriers in fight against AIDS pandemic.

PMID- 11591008
TI  - Prisons. Court allows misdiagnosis claim, dismisses one defendant.

PMID- 11591009
TI  - Appeals court upholds sentence in sale of fake HIV test kits.

PMID- 11591010
TI  - Prisons. Inmates lose challenges in 2 HIV/AIDS treatment cases.

PMID- 11591011
TI  - GAO: infectious disease surveillance faces challenges ahead.

PMID- 11591012
TI  - Vaccine. NIAID says support for research up sixfold since 1990.

PMID- 11591013
TI  - An idea whose time has finally come?

PMID- 11591014
TI  - Certificate of need and the quality of cardiac surgery.
AB  - Historically, states have used Certificate of Need (CON) programs to review
      proposals for new construction and expanded services in an effort to control
      costs and to improve the quality of and promote access to health care services.
      Congressional funding for CON ended in 1987. However, today, 26 states use CON to
      regulate cardiac surgery. There has been little evidence of the impact of CON on
      the quality of services. Pennsylvania is in a unique position to study the impact
      of CON on the quality and outcomes of care because the state terminated CON in
      1996 and has publicly reported quality and outcomes data on coronary bypass graft
      (CABG) surgeries since 1992. Using a statewide inpatient data-reporting system,
      the volumes and outcomes of CABG surgeries at all Pennsylvania hospitals were
      examined in the 3 years prior to and the 3 years after the termination of CON. In
      the 3 years following the elimination of CON, the number of open-heart surgery
      programs increased 25%, yet there was no significant increase in the number of
      CABG surgeries performed. Quality, as measured by mortality rate, was not
      impacted by the real-location of the relatively stable CABG volume in the short
      term; this may be due, in part, to itinerant surgeons and statewide public
      performance monitoring. The long-term implications of deregulation are unclear
      and deserve future study.

PMID- 11591015
TI  - A comparison of predictive outcomes of APACHE II and SAPS II in a surgical
      intensive care unit.
AB  - The Acute Physiologic Score and Chronic Health Evaluation (APACHE) II and the
      Simplified Acute Physiologic Scale (SAPS) II are two of the more commonly
      employed predictors of outcome and performance in the intensive care unit
      setting. However, controversy persists about whether the scores generated by
      these systems have similar predictive value. This study compared the predicted
      mortalities derived from APACHE II and SAPS II and contrasted them to the actual
      mortality in a surgical intensive care unit (SICU). Data for 1665 patients
      admitted to the SICU between July 1994 and August 1997 were entered into an SICU
      computerized database. From recorded demographic, hemodynamic, and laboratory
      data, APACHE II and SAPS II scores were obtained with corresponding predicted
      mortalities. Patients were stratified by age into categories of less than and
      greater than 65 years old. Predicted mortalities by APACHE II and SAPS II were
      compared for each group. An additional analysis included a comparison of
      survivors and nonsurvivors. There was no significant difference in predicted
      mortality between APACHE II and SAPS II in any of the groups. Actual mortality
      was 30 of 486 (6.2%) in patients less than 65 years of age and 73 of 1179 (6.2%)
      in patients 65 years of age or greater. The APACHE II and SAPS II predicted
      mortalities (mean +/- SD) for patients less than 65 years of age were 10.5% +/-
      10.6% and 10.9% +/- 13.3%, respectively (P > .05). The APACHE II and SAPS II
      predicted mortalities in patients 65 years of age or greater were 19.1% +/- 17.8%
      and 18.7% +/- 21.0%, respectively (P > .05). Similarly, when patients were
      stratified by survival status, no significant difference was present between
      groups. However, in individual patients, a difference between APACHE II and SAPS
      II scores was often present. We conclude that although disparities between APACHE
      II and SAPS II predicted mortalities in individual patients may be significant,
      APACHE II and SAPS II have similar predictive value in a large SICU patient
      population. However, both APACHE II and SAPS II systems overestimate mortality in
      SICU patients. Based on our results, we conclude that either system can be used
      to measure quality of care in the SICU; however, neither system can be reliably
      applied to a single patient.

PMID- 11591016
TI  - Health status and satisfaction with health care: a longitudinal study among
      patients served by the Veterans Health Administration.
AB  - As the Veterans Health Administration (VHA) places high priority on becoming a
      performance-based organization, there is an increasing need to quantify and
      refine its outcome measurement system. Using panel data from VHA ambulatory care
      patients (1996-1998), we conducted cross-lagged correlations and ordinary least
      squares regression to examine the relationship between 2 VHA health care values:
      health status and satisfaction with care. The study results indicated that
      patients' health status was significantly associated with their satisfaction with
      care, indicating that patients with better health status were more likely to be
      satisfied with health care. Although satisfaction with care was both a
      consequence and a determinant of health status, the effects of health status on
      satisfaction seemed to be more important than the effects of satisfaction on
      health status. More research is needed for a better understanding of the dynamic
      relationship between health status and satisfaction with care.

PMID- 11591017
TI  - Pediatric hospitalists: quality care for the underserved?
AB  - Despite the rapid growth in pediatric hospitalist services, there is little
      empiric information about the impact of pediatric hospitalists. This study
      compared process and outcome variables related to the inpatient care of 182
      pediatric patients, half of whom were cared for by hospitalists and half by their
      primary care providers (PCP). Results indicated that, while hospitalists cared
      for patients of substantially lower socioeconomic status, they delivered care
      more economically for patients with asthma, with no significant differences in
      rates of return to the emergency room or rehospitalizations. Children in both
      services demonstrated equivalent levels of returning to their PCP for follow-up
      visits and were in equally good health 1 month after discharge. Additionally, no
      negative impact was evident on patient satisfaction at discharge; in fact, the
      hospitalists' patients were more satisfied with aspects of their care.
      Hospitalists may, therefore, provide a vital service by ensuring quality
      inpatient care for low-income children.

PMID- 11591018
TI  - [Current and future strategies in interdisciplinary treatment of
      medulloblastomas, supratentorial PNET (primitive neuroectodermal tumors) and
      intracranial germ cell tumors in childhood].
AB  - BACKGROUND: The chances for cure in medulloblastoma, supratentorial primitive
      neuroectodermal tumors (stPNET) and intracranial germ cell tumors have decisively
      improved within the last decades. Today long-term survival in the range between
      60% and 80% and more than 90%, respectively, can be achieved. The low incidence
      of brain tumors in childhood and the necessity for optimal patient care has led
      to the fact that more than 90% of children are treated within national and
      international controlled studies today in order to assure a constant improvement
      of therapeutic outcome. Recent developments in neurosurgery achieved complete
      tumor resections in the majority of children at a low risk for morbidity and
      mortality. METHODS: Systemic irradiation of neuroaxis is an essential part in the
      management of medulloblastoma, stPNET and intracranial germ cell tumors. The
      introduction of quality assurance programs in radiooncology assures a precise
      radiotherapy of target volumes and is a prerequisite to improve survival.
      RESULTS: Hyperfractionated radiotherapy has the potential of increasing dose to
      tumor more safely without increasing the risk for late adverse effects. Pilot
      studies revealed excellent tumor control in medulloblastoma with acceptable acute
      toxicity and a long-term survival of up to 96%. In medulloblastoma stereotactic
      radiation techniques reveal an acceptable toxicity and promising results in tumor
      control in recurrent disease or as primary treatment. They are now part of future
      treatment protocols in case of persisting residual tumor. Radiotherapy alone in
      pure germinoma is continuously yielding high cure rates. In secreting germ cell
      tumors cisplatin containing chemotherapies in conjunction with radiotherapy
      achieve a long-term survival rate of 80% today. Especially in high risk
      medulloblastoma and secreting germ cell tumors chemotherapies are playing an
      increasingly important role in the interdisciplinary management. It can be
      expected that future developments of chemotherapeutic protocols and the
      introduction of new cytostatic substances will further improve the therapeutic
      outcome. CONCLUSIONS: The therapeutic endeavors of all those caring for children
      are aiming to study modifications of the therapeutic components in the
      interdisciplinary approach in order to optimize the therapeutic strategies. In
      future the affected children and young adolescents should be accrued for the
      forthcoming cooperative, prospective trial HIT 2000 and ongoing trial SIOP CNS
      GCT 96, respectively, in order to provide the body of data supporting the
      selection of novel and optimized approaches for future treatment strategies.

PMID- 11591019
TI  - Predictive value of the tumor oxygenation by means of pO2 histography in patients
      with advanced head and neck cancer.
AB  - PURPOSE: The purpose of this analysis was to evaluate the potential of the tumor
      oxygenation by means of Eppendorf pO2 histography as a predictive test to select
      patients for treatment alternatives. PATIENTS AND METHODS: Pretreatment tumor pO2
      histographies of locoregional lymph node metastases were assessed in 194 patients
      with squamous cell carcinoma of the head and neck. Included in the analysis were
      134 patients who received a primary radio- or radiochemotherapy with a radiation
      dose of > or = 60 Gy, and who had no distant metastasis at beginning of the
      therapy. RESULTS: The Cox regression analysis revealed the fraction of pO2 values
      < or = 2.5 mm Hg (p = 0.004), age (p = 0.04) and radiotherapy/radiochemotherapy
      (p = 0.03) as significant independent prognostic factors for the survival. The
      positive and negative predictive values were calculated using different cut-off
      values of the fraction of pO2 values < or = 2.5 mm Hg and the survival status at
      1 or 2 years after beginning of the therapy as endpoint. The highest positive and
      negative predictive values of all cut-off values were 0.50 and 0.41 at 1 year,
      and 0.81 and 0.26 at 2 years. CONCLUSIONS: Our data confirm the influence of the
      tumor oxygenation on the prognosis of patients with squamous cell carcinoma of
      the head and neck after radiotherapy. However, the calculated positive and
      negative predictive values suggest that the pO2 histography alone is not
      sufficient to be used as a predictive test to successfully select patients for
      treatment alternatives.

PMID- 11591020
TI  - Tumor hypoxia and systemic levels of vascular endothelial growth factor (VEGF) in
      head and neck cancers.
AB  - BACKGROUND: Hypoxia is the most important stimulus for the up-regulation of
      vascular endothelial growth factor (VEGF), one of the key cytokines for
      angiogenesis. We have investigated the possible relationship between tumor
      hypoxia and systemic levels of VEGF. PATIENTS AND METHODS: 56 patients with head
      and neck cancers underwent measurement of tumor volume (pretreatment CT scans),
      tumor oxygenation (pO2 histography) and serum levels of VEGF. The hemoglobin
      level ranged from 9.1 to 16 g/dl. The absolute amount of hypoxic tumor (hypoxic
      tumor volume) was determined as the product of the absolute tumor volume and the
      relative frequency of hypoxic (< 5 mm Hg) measurements in the pO2 histography.
      RESULTS: The serum VEGF levels in the 56 head and neck cancer patients ranged
      from 102 to 1699 pg/ml (median 405 pg/ml, mean 527 +/- 396 pg/ml). Elevated serum
      VEGF levels (> 700 pg/ml) were found in 14/56 patients (25%). Serum-levels of
      VEGF were significantly and independently correlated with hypoxic tumor volume
      (R2 = 0.63, p < 0.001), but also with total tumor volume, hemoglobin levels,
      platelet counts and tumor hypoxia. There was no correlation with T and N
      category, histological grading, and age. CONCLUSIONS: The strong and independent
      impact of the hypoxic tumor volume on systemic VEGF levels suggests that the
      absolute amount of hypoxia within a tumor represents the most important stimulus
      for up-regulation of angiogenesis. Anemia acts as a co-factor via worsening of
      tumor tissue oxygenation.

PMID- 11591021
TI  - Modulation of radioprotective effects of respiratory hypoxia by changing the
      duration of hypoxia before irradiation and by combining hypoxia and
      administration of hemopoiesis-stimulating agents.
AB  - AIM: Analysis of radioprotective effect of respiratory hypoxia on hemopoietic
      tissue and enhancement of this effect by hemopoietic activation. MATERIAL AND
      METHODS: In mice breathing hypoxic gas mixture during total body gamma
      irradiation the recovery of pluripotent and committed granulocyte-macrophage
      progenitor cells and animal lethality were determined. RESULTS: In mice forced to
      breathe 10% O2 and 8% O2 during irradiation, the oxygen tension in the spleen
      decreased to 40% and 20%, respectively, of control values. Hypoxia mitigated the
      lethal effect of gamma-rays and improved the recovery of hemopoiesis in
      compartments of pluripotent and committed progenitor cells. Enhancement of the
      proliferative activity in hemopoietic tissue by a cytokine (rmGM-CSF) or an
      immunomodulator (dextran sulfate) increased the effect of hypoxic
      radioprotection, while elimination of proliferative cells by hydroxyurea
      decreased the radioprotective effect. Adaptation of experimental animals to
      hypoxic conditions was found to reduce the radioprotective effect without
      influencing tissue partial oxygen pressure lowered by hypoxic conditions.
      CONCLUSION: The data presented confirm the radioprotective effect of 10% and 8%
      O2 respiratory hypoxia on hemopoiesis. These findings may represent a way out for
      further experimental and clinical research aimed at considering differential
      protection of various tissues by hypoxia.

PMID- 11591022
TI  - The efficiency and tolerance of half-body irradiation (HBI) in patients with
      multiple metastases. The Krakow experience.
AB  - AIM: To present our experience regarding the efficiency and tolerance of half
      body irradiation in patients with multiple cancer metastases. PATIENTS AND
      METHODS: Between January 1986 and December 1997, 102 patients with multiple
      cancer metastases received half-body irradiation (HBI) at the Center of Oncology-
      Maria Sklodowska-Curie Memorial Institute in Krakow. Most of the patients
      (93/102) had bone metastases (Table 1). The HBI was performed with 9 MV photon
      beam from linear accelerator. In 88 patients only one region (upper, mid or
      lower) was treated, and 14 patients received upper and lower HBI (13 patients),
      or upper and mid HBI (one patient) (Table 2). The mean doses were: 6 Gy in upper
      HBI, 8 Gy in mid HBI, and 9 Gy in lower HBI (Table 3). RESULTS: The positive
      palliative effect (complete or partial pain relief) was observed in 77 (75.5%)
      patients (Table 4). Complete pain relief was higher in patients with prostate
      cancer, and in patients who received mid or lower HBI. During follow-up 47
      (46.1%) patients developed pain progression after treatment (Table 5). The
      probability of survival without pain progression was higher in patients who
      developed complete pain relief (86.7% at 6 months, 69.3% at 12 and 24 months)
      than in patients with partial response (52.9% at 6 months, 32.8% at 12 months,
      and 5.5% at 24 months) (Figure 1). In most of the patients (74/102, 72.5%) the
      tolerance was good. CONCLUSIONS: HBI is an efficient method for palliation in
      patients with multiple painful metastases.

PMID- 11591023
TI  - [Recall dermatitis caused by re-exposure to docetaxel following irradiation of
      the brain. Case report and review of the literature].
AB  - BACKGROUND: Together with radiation therapy the taxanes Paclitaxel and Docetaxel
      are more and more integrated into multimodal therapy regimens concerning breast-
      and lung cancer as well as squamous cell carcinoma of the head and neck.
      Especially in palliative situations we have to be aware of increasing side
      effects caused by interaction of the different treatment components. Therefore we
      report on a severe recall dermatitis that occurred in two breast-cancer patients
      following irradiation of the brain and reexposition to Docetaxel. PATIENTS AND
      METHOD: From January until March 1999 two female patients suffering from
      metastatic breast cancer and newly diagnosed cerebral metastases respectively
      carcinomatous meningitis underwent irradiation of the whole brain (2 Gy 5
      days/week up to a reference dose of 50 Gy) in our department. Both patients had
      several courses of Docetaxel (Taxotere) 30 mg/m2 BSA weekly respectively 100
      mg/m2 BSA/month since October and November 1998. After completion of radiotherapy
      chemotherapy with Docetaxel was continued. RESULTS: Both patients tolerated
      Docetaxel well before and during radiotherapy. However, after having finished
      irradiation of the brain and receiving Docetaxel again a severe erythema of the
      irradiated skin and large areas of moist epitheliolysis with crust occurred (CTC
      grade IV). CONCLUSION: The dermatitis related to irradiation and reexposition to
      Docetaxel observed in our two cases is interpreted as a recall reaction. The
      basic initiating pathologic mechanism has not been solved completely. Further
      investigation is needed to find out how the taxanes can be used in combination
      radiochemotherapy regimens without causing severe toxicity to the irradiated skin
      or mucosa.

PMID- 11591024
TI  - [IFN-alpha consolidation after intensive chemotherapy does not bring any survival
      advantage in low-grade non-Hodgkin lymphoma].

PMID- 11591025
TI  - [Effects of an adjuvant mistletoe therapy in patients with surgically treated
      head and neck neoplasms: a randomized clinical trial].

PMID- 11591026
TI  - Municipal hotlines and automated weather stations as a tool for monitoring bad
      odour dispersion: the northern Negev case.
AB  - Bad odours are often dispersed from chemical industries, waste dumps, sewer
      plants, and other facilities. They are indicative of pollution emissions from
      these sites and cause discomfort, apprehension, and sometimes signal the presence
      of health hazards. Monitoring the pollution by direct means, such as chemical
      analysis of ambient air, is obviously the most reliable mechanism to acquire data
      regarding pollution. However, this is not always possible. In this paper we
      report on the value of local government hotlines that record information provided
      by the public regarding bad odours. These data can alert the authorities to the
      existence of pollution and should be regarded as potentially useful when
      collected in conjunction with information from automated weather stations. An
      analysis of data from the Be'er Sheva municipality and the Ramat Negev regional
      council hotlines is provided. Complaints recorded by these systems were
      correlated with weather data from local automatic weather stations to indicate
      the sources of the bad odours. Wind direction was found to be highly correlated
      with bad odour and pollution sources, revealing consistent patterns in terms of
      the time of day and weather conditions.

PMID- 11591027
TI  - A note on the use of the analytic hierarchy process for environmental impact
      assessment.
AB  - Environmental impact assessment (EIA) is an intrinsically complex multi
      dimensional process, involving multiple criteria and multiple actors. Multi
      criteria methods can serve as useful decision aids for carrying out the EIA. This
      paper proposes the use of a multi-criteria technique, namely the analytic
      hierarchy process (AHP), for the purpose. AHP has the flexibility to combine
      quantitative and qualitative factors, to handle different groups of actors, to
      combine the opinions expressed by many experts, and can help in stakeholder
      analysis. The main shortcomings of AHP and some modifications to it to overcome
      the shortcomings are briefly described. Finally, the use of AHP is illustrated
      for a case study involving socio-economic impact assessment. In this case study,
      AHP has been used for capturing the perceptions of stakeholders on the relative
      severity of different socio-economic impacts, which will help the authorities in
      prioritizing their environmental management plan, and can also help in allocating
      the budget available for mitigating adverse socio-economic impacts.

PMID- 11591028
TI  - Environmentally sensitive plot-scale timber harvesting: impacts on suspended
      sediment, bedload and bank erosion dynamics.
AB  - The impact on sediment pollution of environmentally sensitive harvesting of a 15
      ha plot (20% of the catchment area) of mature coniferous plantation forest in the
      0.89 km2 Afon Tanllwyth catchment, Plynlimon, was investigated for 12 months
      before harvesting began and a further 18 months after. The results revealed: (a)
      a steepening of the suspended sediment concentration vs. discharge rating curve
      resulting in a 39% increase in suspended sediment yield (as compared to the
      adjacent forested Hafren catchment) during the year in which the harvesting
      operations took place; (b) a statistically significant increase in main channel
      bank erosion rates, as compared with the nearby Afon Cyff; main channel banks are
      estimated to have contributed around 80% of the total catchment suspended
      sediment yield during the two year period (1995-1996), and (c) no significant
      change in bedload yields over the duration of the study, though a longer post
      harvesting time series of bedload data will be required to properly assess the
      impact of the harvesting operation upon bedload yields. Forest management
      implications of these findings are discussed in detail with respect to the
      existing Forest and Water guidelines.

PMID- 11591029
TI  - Decline of the mountain acacia, Brachystegia glaucescens in Gonarezhou National
      Park, southeast Zimbabwe.
AB  - The objectives of the study were to investigate the role of fire and other
      factors in the decline of the mountain acacia, Brachystegia glaucescens Burtt
      Davy & Hutch. in the northern region of the Gonarezhou National Park, southeast
      Zimbabwe. The study site, which is a wilderness area, has suffered a succession
      of fires which, coupled with elephant pressure and drought, has reduced what was
      once woodland into scrubland. With the grass continuously burnt off, very few
      grazing animals can be found in the area and erosion of the unprotected slopes
      has left it rocky and barren. The paper attempts to analyse field observations
      using established ordination and statistical procedures. The conclusions that
      both fire and elephant damage are powerful factors leading to loss the loss of B.
      glaucescens woodland are established. The findings should be considered in
      setting management goals and monitoring their effects, particularly in measures
      that encourage restoration of the woodland.

PMID- 11591030
TI  - Regional planning for the siting of local evaporation basins for the disposal of
      saline irrigation drainage: development and testing of a GIS-based suitability
      approach.
AB  - In order to prevent salinisation of the streams of the Riverine Plain of the
      Murray-Darling Basin in southern Australia, evaporation basins are used to
      dispose of saline irrigation drainage water. Local on-farm (individual
      landholder) and community (shared between multiple landholders) basins are
      increasingly being used to prevent export of salt outside irrigation districts.
      There are questions regarding the availability of land suitable for these basins
      and their impact on the surrounding environment. We describe the use of currently
      available spatial data to assist in regional planning for the environmentally
      safe use of these basins. A GIS-based approach was developed using suitability
      criteria expected to minimise the risk of off-site effects of basin leakage. The
      criteria were proximity to surface water features, urban areas and
      infrastructure, water table depth and salinity, and soil hydraulic conductivity.
      The approach was applied to all of the major irrigation districts at 1:250,000,
      the scale at which data are available over the entire Riverine Plain. Confidence
      in well-defined parameters such as proximity to infrastructure, urban areas and
      surface water features was higher than for those involving interpolated point
      data such as water table depth, salinity, and hydraulic conductivity. Most
      critically, hydraulic conductivity, the most important factor for basin leakage,
      was found to be unreliable at this scale. Use of higher resolution data (up to
      1:100,000) available for two of the irrigation districts improved confidence in
      both water table depth and salinity but not in hydraulic conductivity. Despite
      these limitations, it was found that: (i) on-farm basins can only be used on an
      opportunistic basis in the eastern irrigation districts, but can be widely used
      in the western districts; (ii) community basins can be used anywhere there is
      suitable land; and (iii) the results raise serious questions as to whether there
      is enough suitable land in the eastern districts to dispose of all of the
      drainage water that is produced.

PMID- 11591031
TI  - Environmental issues in the post-communist Ukraine.
AB  - The Ukraine, which gained independence in 1991, faces serious problems related to
      environmental degradation. Environmental problems contribute to a deterioration
      in human health and a negative trend in population growth. Both form part of a
      raft of socio-economic problems encountered during the country's transition to a
      free market economy. The most serious problems are found in cities and areas near
      the Black and Azov Seas, the Dnipro river basin and in the Polissya region. This
      paper provides an overview of the situation. Social and managerial implications
      of environmental management are considered alongside associated environmental and
      human health problems in the country. It is concluded that a desired change in
      the mindset of policy makers and, indeed, the population at large, is required in
      parallel with legal and technocratic instruments, while real improvements can
      only be achieved through economic development, which can be facilitated by
      Western assistance.

PMID- 11591032
TI  - The effect of limited options and policy interactions on water storage policy in
      south Florida.
AB  - Due to environmental constraints and reactive water management practices, water
      shortages exist across the Everglades ecosystem. A growing human population and
      continued wetlands damage and loss decrease the system's ability to provide water
      for sustained natural areas and for human uses. 'The Restudy' is an $8 billion
      plan to restore the Everglades while also continuing to provide water storage for
      urban and agricultural areas. The Restudy proposes a mix of water storage systems
      to provide for the predicted future growth in water demand. This mix is purported
      to be the most cost-efficient at providing water supplies, within the constraints
      of unchanged agricultural and urban land use. However, a sensitivity analysis of
      the Restudy's cost equation reveals that the total cost of water storage systems
      is influenced by real estate, land acquisition and water treatment costs. The
      interaction of land use and agricultural policies can affect these cost factors,
      and can change the relative cost-efficiency between storage systems. Real estate
      and land acquisition costs are affected by several 1996 Farm Bill provisions,
      which influence the cost of aboveground water storage systems versus Aquifer
      Storage and Recovery systems. The Governor's Commission for a Sustainable South
      Florida recommendations also influence the water storage options available to the
      Restudy. Due to the Restudy's initial assumptions and constraints, it may not
      advocate the most economically and ecologically sound remediation.

PMID- 11591033
TI  - Making angioplasty last longer.

PMID- 11591034
TI  - Robotics: the next step in less invasive surgery.

PMID- 11591035
TI  - Is it a floater--or a detached retina?

PMID- 11591037
TI  - I have trouble using my hearing aid when there is background noise. How can I
      improve its effectiveness?

PMID- 11591038
TI  - Should I consider surgery for my hernia, or can I continue using a truss?

PMID- 11591036
TI  - Heading off recurrent headaches.

PMID- 11591039
TI  - American Association of Cardiovascular and Pulmonary Rehabilitation telemedicine
      position statement.

PMID- 11591040
TI  - Transforming exercise-based cardiac rehabilitation programs into secondary
      prevention centers: a national imperative.

PMID- 11591041
TI  - Team management of heart failure: the emerging role of exercise, and implications
      for cardiac rehabilitation centers.

PMID- 11591042
TI  - Return to flight status after cardiac rehabilitation: three case histories.
AB  - A pilot's license to operate aircraft is not valid unless it is accompanied by a
      medical certificate. This certificate is revoked if a pilot is diagnosed with a
      cardiovascular illness. After a lengthy waiting period, the medical certificate
      may be reinstated if the pilot meets rigid standards. For many pilots,
      participation in a cardiac rehabilitation program is essential to achieve the
      minimal functional capacity in exercise testing (10.0 metabolic equivalents),
      document tolerance of medications, and achieve successful rehabilitation. Our
      staff has assisted 11 pilots in their quest to resume commercial or recreational
      flying after heart surgery, pacemaker implantation, or angioplasty. This article
      summarizes the case histories of three pilots who returned to fight status, in
      three Federal Aviation Administration categories (FAA), after a cardiac illness.
      The principle goals of our rehabilitation program for pilots are: (1) to achieve
      the highest possible outcome of the rehabilitation process; (2) to establish a
      safe and effective independent exercise program; (3) to obtain measures of
      compliance and success with the independent exercise program; (4) to document
      tolerance of medications and ensure that medications are acceptable to the FAA;
      (5) to document stability of the serum glucose in diabetic patients engaged in
      rigorous, prolonged exercise; and (6) prepare the patient for performance of a
      treadmill test in which 100% predicted maximum heart rate is achieved without
      symptoms of cardiovascular distress. An inherent effect of pursuing these goals
      is dramatic risk factor modification including improved blood pressure and lipid
      status and reduced body mass index. After resumption of flying, none of our pilot
      patients have experienced cardiac symptoms during flight, nor have they required
      emergency department visits or hospitalization for any reason.

PMID- 11591043
TI  - The impact of nutritional depletion in chronic obstructive pulmonary disease.
AB  - Nutritional depletion is prevalent in patients with advanced chronic obstructive
      pulmonary disease (COPD). These nutritional abnormalities are pronounced in
      patients with the "emphysematous" form of COPD on chronic corticosteroid therapy.
      The pathophysiologic mechanisms for the involuntary weight loss appear to be
      multifactorial. Clinical research has revealed that nutritional depletion in
      advanced COPD is associated with an increased morbidity and mortality. This
      review will address the implications of nutritional depletion in addition to
      potential therapeutic options.

PMID- 11591044
TI  - Chronic obstructive pulmonary disease stage and 6-minute walk outcome.
AB  - PURPOSE: Although physicians generally reserve pulmonary rehabilitation (PR)
      referral for patients in later stages of chronic obstructive pulmonary disease
      (COPD), there is no evidence to suggest that PR programs are more effective for
      these persons than for those in earlier stages of the disease. This study
      examined the relationship between 6-minute walk change and COPD stage in patients
      completing PR. METHODS: The sample consisted of 76 patients who enrolled in the
      University of Alabama at Birmingham's Cardiopulmonary Rehabilitation Program with
      a primary diagnosis of COPD between January 1996 and June 2000. Data was
      collected on 6-minute walk upon entry into the program and upon program
      completion. Patients were stratified according to COPD stage using the American
      Thoracic Society staging system. RESULTS: There were significant differences
      among the three stages with regard to initial and ending 6-minute walk distances
      such that persons in later stages of the disease have shorter initial and ending
      6-minute walk distances. However, all three stages show significant improvements
      in the 6-minute walk after PR. There were no significant differences in the
      median change among groups indicating that the median change was not better (or
      worse) for patients in any particular COPD stage. CONCLUSIONS: This study
      suggests that PR is equally effective in increasing physical performance for all
      patients regardless of COPD stage. This type of information can be used to
      support the recommendation of PR for patients early in the disease process.

PMID- 11591045
TI  - Polymyalgia rheumatica revisited.

PMID- 11591046
TI  - Isonymy, consanguinity and repeated pairs of surnames in Aromun populations.
AB  - The Aromuns represent a small and almost unknown people that live scattered over
      the Balkan Peninsula. Due to their language, that is very similar to classical
      Latin, they are in a special position. The Aromuns settled only in more recent
      times. Until now they lived as shepherds, as caravan guides and merchants and
      lead a semi-nomadic life. We are currently carrying out studies to determine the
      genetic structure of this population. To facilitate the interpretation of these
      data, we are also trying to obtain other important parameters that pertain to
      migration processes and the genealogical structure of this populations. The data
      arise from three areas in Albania, the Republic of Macedonia and Romania. The
      inbreeding coefficient and the proportion of repeated pairs of surnames was
      calculated through the use of genealogies and the isonymy method. The difference
      between these three populations are due primarily to confounding by selection of
      mates and family composition.

PMID- 11591047
TI  - Population genetic studies in the Balkans. I. Serum proteins.
AB  - Within a study of the genetics of Southeastern European populations seven serum
      protein polymorphisms (AMY2, BF, C3, CP, GC, HPA, TF) were examined in three
      samples of Aromuns (Albania: the village of Andon Poci, province Gjirocaster,
      Republic of Macedonia: Stip region, Romania: the village Kogalniceanu, province
      Dobruja) and four reference samples (Albanians: Tirana, Romanians: Constanta and
      Ploiesti as well as Greeks (Northeastern Greece)). The Aromun samples from
      Albania and Romania form one separate cluster and the reference samples together
      with the Aromuns from Macedonia (Stip region) form a second one.

PMID- 11591048
TI  - Population genetic studies in the Balkans. II. DNA-STR-systems.
AB  - Within a study of the genetics of Southeastern European populations four DNA-STR
      systems (D21S11, FGA, TH01, VWA) were examined in seven samples (samples of three
      Aromuns and four other Balkan populations). The results have been compared to
      data from four samples from literature (Austrians, Germans, Hungarians,
      Slovenians). The results show three clusters: a) the Aromuns from Albania (Andon
      Poci) and Macedonia (Stip region), b) the Romanian Aromuns (Kogalniceanu),
      Romanians (Constanta, Ploiesti) and Albanians (Tirana) und c) the data from
      literature. A sample of Northeastern Greece clearly differs from these three
      clusters. Including seven serum protein polymorphisms (without the populations
      from literature) results in two clusters: a) the three Aromun populations and b)
      Albanians and Romanians. Again the sample of Northeastern Greece clearly differs
      from these clusters.

PMID- 11591049
TI  - [Variability of blood group frequencies in Romania].
AB  - This paper presents the results of a study of two population samples from Dobruja
      and Muntenia (Romania) as well as data from the literature (AB0, MN, Rhesus (D/d)
      and HPA). The data have been pooled according to the different regions of
      Romania. Interestingly, the Carpathian Mountains do not form a genetical barrier:
      there are clear genetical similarities between the provinces east and west as
      well as between the provinces south and north from the mountains. The differences
      and similarities between Romania as a whole and other populations in this region
      reflect the historical processes of the last centuries.

PMID- 11591050
TI  - [Genetic studies in the Cologne administrative district (North Rhine-Westphalia,
      Germany): DNA-STR systems FGA, TH01, VWA and YNZ22].
AB  - The DNA-STR systems FGA, TH01, VWA, YNZ22 have been studied in two German
      population samples (Eschweiler, Stolberg and Hurtgenwald, Inden, Langerwehe,
      administrative area of Cologne, Northrhine-Westphalia). The cluster analysis,
      including data from Dusseldorf, Germany and from Poland, resulted in a cluster
      with Eschweiler, Stolberg and Dusseldorf, separating to a certain degree
      Hurtgenwald, Inden, Langerwehe and Poland more clearly. In contrary to the
      expectations (based on the history of the migration from Northeastern Europe to
      Northrhine-Westfalia) and the results of the study of 22 hemogenetic systems
      (Scheil & Huckenbeck 2000) there was a somewhat larger genetic distance between
      Eschweiler, Stolberg and Poland than between Hurtgenwald, Inden, Langerwehe and
      Poland. The combined data of the four STRs and the 22 hemogenetic systems
      resulted--as expected--in smaller genetic distances between Eschweiler, Stolberg
      and Poland as well as between Dusseldorf and Poland. These different genetic
      distances are interpreted as a result of the migration from North-East Europe to
      North Rhine-Westphalia in the last 130 years and the selective geographic
      distribution of the migrants in the industrial and urbanised areas.

PMID- 11591051
TI  - [DNA PCR typing of non-human primates].
AB  - Human beings and non human primates show similarities in the non coding DNA range
      too, but up to now there are only a few data. This paper presents first results
      of a study dealing with a larger spectrum of species and individuals, considering
      the genetic marker HLA-DQA1, LDLR, GYPA, HBGG, D7S8, GC (partionally coding) and
      VWA, FES, F13B, TH01, CD4, FGA (not coding). The results show that not only the
      apes can be typed but also Macaca sylvanus as a member of the Cercopithecoidea.
      In contrast to earlier publications there is an unexpected larger similarity
      between the allele ranges of the apes studied and those of human beings.

PMID- 11591052
TI  - [Body height, body weight and body mass index of German military recruits.
      Historical retrospect and current status].
AB  - Surveys of conscripts give a chance to pursue the somatic development and the
      nourishment situation of young men over long times. At the beginning a historical
      view is given of the organization and methodological basis of medical
      examinations of German recruits since the introduction of the general
      conscription at the beginning of the 19th century. Secular changes of the body
      height are sketched out for selected regions of Germany until the middle of the
      20th century. Data of the body weight hardly exist for this time. Until now the
      greatest continuous documentation of data for body height and body weight is
      available for West Germany since 1957 and for East Germany between 1973 and the
      reunion in 1989. The body height of German conscripts has nearly permanently
      increased since 1957 and reached in 1994 a maximum with 180.0 cm. In general East
      German conscripts have body height data which are smaller on an average than
      those of West German conscripts. But in the last years a catch-up in body height
      could be seen. The body weight of German conscripts also shows an increase apart
      from some short-time exceptions. The data of West German conscripts are also
      higher than those of the East German conscripts. Until the reunion the West-East
      differences could partly be due to the different mustering age. But the
      differences also continue in the nineties despite the now identical mustering
      age. The Body Mass Index (BMI) of the German conscripts (calculated from the
      average values of body height and body weight) is characterized by increments in
      the last years. This indicates greater changes in body weight than in body
      height. The BMI also shows marked West-East-differences. There is no uniform
      tendency in differences between urban and country side regions for body height
      and body weight. On the other hand until now differences between selected
      professional groups are existing. Especially the over-proportional increase of
      the number of conscripts in the higher body-weight-classes requires a further
      continuous analysis of the available mustering data.

PMID- 11591053
TI  - The interaction of waist-hip ratio and conicity index with subcutaneous adiposity
      in two ethnic groups: native British and migrant Pakistani men.
AB  - The objective of the present investigation was to evaluate the relationship
      between two indices of abdominal fatness, the waist-hip ratio (WHR) und conicity
      index (CI), with subcutaneous adiposity (5 trunk and 4 extremity skinfolds) in
      adult native British (n = 262) and migrant Pakistani (n = 100) men, resident in
      Peterborough, East Anglia, England. Both groups had similar body mass index
      (BMI), WHR and CI. Significant ethnic differences (age controlled) were observed
      in mean values for all trunk as well as forearm skinfolds between the two groups.
      The results indicated that, in general, there was no ethnic heterogeneity in the
      relationship (age controlled) of both the indices of abdominal adiposity with the
      skinfolds. However, the distributions, age, age2 and WHR controlled; and age,
      age2 and CI controlled, of subscapular (SUBSF), suprailiac (SUPSF), abdomen
      (ASF), midaxillary (MIDSF), chest (CSF), forearm (FSF) and medial calf (MCSF)
      skinfolds were significantly different between the two groups. Multiple
      regression analyses revealed that Pakistanis had significantly higher mean SUBSF,
      SUPSF, ASF, MIDSF, CSF and significantly lower mean FSF and MCSF than Whites,
      after controlling the effect of WHR. Similar significant ethnic differences were
      observed when the effect of CI was controlled for. This significant association
      of ethnicity remained even when the combined effects of WHR and CI were removed.

PMID- 11591054
TI  - [Homicide by burning].
AB  - Compared to the total number of deaths by heat (burning, scalding), homicides by
      the direct effect of thermal energy (setting the victim on fire, pouring hot
      liquids over them) are rare; accordingly this subject is seldom dealt with in
      forensic and criminological literature. From our own autopsy material three cases
      are presented describing some peculiarities of homicide by heat. Sometimes
      additional findings (e.g., residual traces of gagging or tying) primarily point
      in the direction of homicide.

PMID- 11591055
TI  - [Unusual carbon monoxide poisoning].
AB  - Despite of indicative death scenes or characteristic findings of the external
      examination, about 40% of the accidental fatal intoxications due to carbon
      monoxide are not recognized before the performance of the autopsy. Six cases are
      reported which illustrate possible reasons for the delayed establishment of the
      diagnosis: unusual circumstances of the intoxication or sources of carbon
      monoxide, only subtle degree or lack of external signs of the intoxication or a
      competing cause of death at autopsy.--Cases 1 and 2: 53, respectively 54-year-old
      couple, found dead in a caravan, extreme putrefaction of the bodies,
      spectrophotometric detection of the fatal carboxyhaemoglobin level in oedema
      fluid of the scalp.--Case 3: 23-year-old lorry driver, found dead in the tightly
      closed cab of his lorry, operation of a source of electricity with
      "environmentally friendly" fuel, carboxyhaemoglobin level 83%.--Case 4: 19-year
      old man, found dead in the flat of friends, removal of the CO-source before
      alerting the police forces, lack of the bright pink coloration of livor mortis,
      haemopericardium due to atrial rupture at postmortem examination,
      carboxyhaemoglobin level 65%.--Case 5: 27-year-old man, found dead in his flat,
      advanced decomposition of the body, residues of a charcoal fire in a metal bucket
      in the sink, carboxyhaemoglobin level 80%.--Case 6: 42-year-old woman, lying dead
      in the garage beside her car, engine switched-off, ignition key next to the body
      on the floor under the car, carboxyhaemoglobin level 46%.

PMID- 11591056
TI  - [Chronology of a homicide and an attempted suicide by DNA analysis of selected
      blood stains on the weapon (knife)]].
AB  - A five-year-old boy was fatally injured by a stab and a cut to the throat. The
      suspected offender, an acquaintance of the victim's mother, stated that he had
      been disturbed by the boy while attempting suicide and had therefore killed the
      boy. The suspect showed superficial cuts on both wrists and three shallow stabs
      on the right-hand side of the abdomen. The purpose of the forensic investigations
      was to answer the question if the suspect's statement could be confirmed or if
      the attempted suicide took place after killing the boy. The blood-smeared blade
      of the knife was divided into different sectors with the cutting edge and the tip
      of the blade being examined separately from the sides. The blood traces from the
      different blade sectors were then typed in 12 different DNA regions by PCR
      (polymerase-chain-reaction). It could be demonstrated that the strong blood
      traces on the sides of the blade originated from the victim alone, whereas in the
      area of the edge and the tip of the blade the amount of the victim's blood was
      negligible compared with that of the suspected offender. The explanation for this
      finding is that in the areas of the edge and the tip of the knife the blood of
      the victim must have been replaced by the blood of the suspected perpetrator,
      which means that the suicidal injuries were the last to be caused by the knife.

PMID- 11591057
TI  - [Development of rust stains on the skin due to contact with a gun].
AB  - In order to study the conditions for the formation of so-called rustmarks on the
      skin after contact with weapon steel tests to provoke rustmarks were performed on
      corpses and living bodies. These tests were only successful under the condition
      of a firm contact with the weapon steel and a certain minimum contact time
      between the weapon and the skin. The experiments showed that the critical
      parameters for the appearance of rustmarks are, first, the humidity of the skin
      and the environment, respectively, as well as the contact time, and second, the
      state of the weapon surface (greased or ungreased). Both the ambient temperature
      and the pH value of the skin (alkaline or acid) are irrelevant to the formation
      of rust. The longest time period until rustmarks appeared was observed on dry
      skin in contact with a greased weapon, namely 22 hours on a corpse and 170 min on
      a living subject. When using a greased gun humidity accelerated the formation of
      rust. An ungreased surface of the weapon also resulted in faster rust formation.
      The minimum time necessary for the formation of rust determined under the most
      favourable circumstances was 135 min for a corpse and 27 min for a living person.
      During the early postmortal interval the rustmark may therefore be another piece
      in the jigsaw towards determining the time of death on suicides committed with
      firearms.

PMID- 11591058
TI  - [Death in homes for the aged/nursing homes from the legal medicine viewpoint].
AB  - Following the death of 16 inhabitants of a nursing home within a period of 2
      weeks, the prosecution ordered legal autopsies in all of the cases, which had not
      yet been buried or cremated, suspecting a neglect of nursing or active euthanasia
      respectively. Two out of a total of ten cases revealed drug overdoses which could
      have explained death. However, due to concurring causes of death, the evidence
      could not be furnished with adequate security. In the present case, the
      examinations helped--already in a preliminary stage of the investigations--to
      prevent the authorities from more expensive proceedings as well as the respective
      nursing home from being unjustly suspected of having committed a criminal
      offense.

PMID- 11591059
TI  - [Animal bites caused by a song bird?].
AB  - The report describes a case of post-mortem scavenging by a songbird. A married
      couple had opened the cage of an astrild (finch) prior to their joint death. The
      body of the wife showed unusual patchy epidermal lesions on parts of the body not
      covered by the clothing, which were obviously caused by the songbird. According
      to the observations made by Roll and Rous they are attributable to "pecking and
      pulling". The behaviour of the bird was most probably due to lack of fluid.

PMID- 11591060
TI  - [Simulation of homicide to hide child's suicide].
AB  - A case of pretending a homicide to conceal a child suicide is reported in which
      characteristic findings of the postmortem examination and conclusions from the
      analysis of forensic autopsy series provided substantial support for the police
      investigation. In the late night hours of a spring day the police authorities
      were informed that a 10-year-old girl had been found dead on a playground near
      its parents' house. As injuries of the neck were recognized by the police
      officers a homicide investigation was initiated. The post mortem examination
      showed a furrow symmetrically slanting from the front to the nape of the neck,
      discrete punctate haemorrhages of the skin of the face and numerous 'tram-line'
      bruises of the back, buttocks and extremities. These findings indicated as cause
      and manner of death suicidal hanging following corporal punishment. Confronted
      with these conclusions the mother immediately made a corresponding confession.

PMID- 11591062
TI  - SignStream: a tool for linguistic and computer vision research on visual-gestural
      language data.
AB  - Research on recognition and generation of signed languages and the gestural
      component of spoken languages has been held back by the unavailability of large
      scale linguistically annotated corpora of the kind that led to significant
      advances in the area of spoken language. A major obstacle has been the lack of
      computational tools to assist in efficient analysis and transcription of visual
      language data. Here we describe SignStream, a computer program that we have
      designed to facilitate transcription and linguistic analysis of visual language.
      Machine vision methods to assist linguists in detailed annotation of gestures of
      the head, face, hands, and body are being developed. We have been using
      SignStream to analyze data from native signers of American Sign Language (ASL)
      collected in our new video collection facility, equipped with multiple
      synchronized digital video cameras. The video data and associated linguistic
      annotations are being made publicly available in multiple formats.

PMID- 11591061
TI  - Transcript-based computer animation of movement: evaluating a new tool for
      nonverbal behavior research.
AB  - A new approach for the use of computer animation in experimental nonverbal
      research is introduced. The method was evaluated in a pilot study comparing video
      recordings of movement in dyadic interactions with computer animations based on
      transcripts of the behavior, to determine whether similar impression effects
      could be obtained. At the core of our development is a software tool allowing for
      the conversion of so-called position time-series protocols of movement into
      animation scripts for a professional computer animation platform. Our software
      combines computer-assisted movement transcription and editing with state-of-the
      art 3-D animation technology. We present empirical evidence indicating remarkable
      overall correspondence between video recordings and computer animations. Due to
      the lack of facial activity in the computer animations, a decline in visual
      attention for the face area could be observed, which did not, however, affect the
      impression ratings.

PMID- 11591063
TI  - Beyond ba-ba and gu-gu: challenges and strategies in coding infant vocalizations.
AB  - Infant vocal behaviors are extremely complex. Consequently, coding these
      behaviors is difficult and is typically associated with low reliability across
      observers. Various difficulties that arise when dealing with prelinguistic
      vocalizations, especially in the first 6 months of life, are outlined here. A
      proposed database of digitized infant vocalizations that illustrates strategies
      used to deal with these difficulties is then described. These strategies are
      based on theoretical infraphonological constructs, empirical observations, and
      information about the nature of mature phonological systems. Furthermore, the
      strategies are open-ended and can be modified as new information becomes
      available regarding infant vocal behaviors. At present, a preliminary database is
      available on the Web that illustrates some of these strategies. As the database
      is expanded, it is expected to provide a general framework for observers to
      categorize infant vocalizations and thereby enhance observer reliability.

PMID- 11591065
TI  - Observation and judgment in psychology: assessing agreement among markings of
      behavioral events.
AB  - In a sequence from a videotaped dialogue between two persons (e.g.,
      psychotherapist and patient), observers are given the task of searching for,
      marking, and commenting on conspicuous events. The observers receive no
      information on where to look for conspicuous events and no information on what
      events are worth marking. Moreover, nothing is known about the observers' marking
      preferences. Marking is therefore very spontaneous and subjective. This marking
      freedom leads to the problem that a superimposition of all observers' markings
      yields complicated configurations of mutually overlapping intervals. To address
      this difficulty, a new definition of the concept of marking agreement is proposed
      that is based upon relational considerations. According to this definition, a set
      of agreeing marking subsets of various sizes can be found in marking
      configurations. A significance concept is proposed to allow comparison of
      different configurations, and standardization on the basis of random
      configurations is performed using Monte Carlo simulations.

PMID- 11591064
TI  - Comparing sequential associations within a single dyad.
AB  - We present a new application of sampled permutation testing to examine whether
      two sequential associations are different within a single dyad (e.g., a teacher
      and a student). A Monte Carlo simulation with the same (i.e., 100 vs. 100) or a
      different (100 vs. 400) number of event pairs was used to simulate designs that
      use time-based (typically producing equal-length comparisons) and event-based
      (typically producing different-length comparisons) data, respectively. For these
      pairs of simulated data streams, we compared the Type I error rates and the kappa
      for agreement on significance decisions, using the sampled permutation tests and
      the more traditional asymptotic log linear analysis. The results provide the
      first evidence relevant to evaluating the accuracy of log linear analysis and
      sampled permutation testing for the purpose of comparing sequential associations
      within a single dyad.

PMID- 11591066
TI  - Measuring daily behavior using ambulatory accelerometry: the Activity Monitor.
AB  - Advanced ambulatory systems that measure aspects of overt human behavior during
      normal daily life have become feasible, owing to developments in data recording
      and sensor technology. One such instrument is the Activity Monitor (AM). This
      paper provides a technical description of the AM and information about its
      validity and current applications. The AM is based on ambulatory accelerometry,
      the aim of which is to assess postures and motions for long-term (> 24-h)
      measurement periods during normal daily life. Accelerometers are attached to the
      thighs, trunk, and lower arms, and signals are continuously stored in a digital
      portable recorder. In the postmeasurement analysis, postures and motions are
      detected by means of custom-made software programs. Validity studies performed on
      different populations showed high agreement scores between the computerized and
      automatic AM output and the visually analyzed video recordings. The AM has so far
      been applied in rehabilitation, psychophysiology, and cardiology but has many
      possibilities in behavioral research.

PMID- 11591067
TI  - Ambulatory accelerometry to quantify involuntary movements and tics in the
      syndrome of Gilles de la Tourette.
AB  - Gilles de la Tourette syndrome is a chronic neuropsychiatric disorder
      characterized by recurrent and involuntary tics, in addition to complex
      behavioral symptoms. Objective quantification of the nonspecific movements in
      Tourette patients can contribute much to understanding the pathophysiology of
      this disease. We used three accelerometers to characterize head movement patterns
      and to objectively quantify head motility in the lateral, sagittal, and
      transversal planes in 9 Tourette patients and 14 controls during periods of rest,
      conversation, and watching a videotape with an entertaining program.
      Characteristic head movement patterns can be documented by means of
      accelerometry. Head motility levels in the lateral, sagittal, and transversal
      planes were significantly higher in the patients than in the controls during all
      the procedures. The patients and the controls showed a similar significant
      increase in head motility during conversation, but not during video watching.
      This first study shows that for both standardized and ambulatory research,
      accelerometry may provide an objective tool by which to quantify the severity and
      temporal dynamics of tics or nonspecific movements.

PMID- 11591068
TI  - Computer-aided method for calculating animal configurations during social
      interactions from two-dimensional coordinates of color-marked body parts.
AB  - In an experiment investigating the impact of preweaning social experience on
      later social behavior in pigs, we were interested in the mutual spatial positions
      of pigs during paired social interactions. To obtain these data, we applied a
      different colored mark to the head and back of each of 2 pigs per group and
      videotaped the pigs' interactions. We used the EthoVision tracking system to
      provide x,y coordinates of the four colored marks every 0.2 sec. This paper
      describes the structure and functioning of a FoxPro program designed to clean the
      raw data and use it to identify the mutual body positions of the 2 animals at 0.2
      sec intervals. Cleaning the data was achieved by identifying invalid data points
      and replacing them by interpolations. An algorithm was then applied to extract
      three variables from the coordinates: (1) whether the two pigs were in body
      contact; (2) the mutual orientation (parallel, antiparallel, or perpendicular) of
      the two pigs; and (3) whether the pig in the "active" position made snout contact
      in front of, or behind, the ear base of the other pig. Using these variables, we
      were able to identify five interaction types: Pig A attacks, Pig B attacks,
      undecided head-to-head position, "clinch" resting position, or no contact. To
      assess the reliability of the automatic system, a randomly chosen 5-min
      videotaped interaction was scored for mutual positions both visually (by 2
      independent observers) and automatically. Good agreement was found between the
      data from the 2 observers and between each observer's data and the data from the
      automated system, as assessed using Cohen's kappa coefficients.

PMID- 11591069
TI  - Versatile computerized system for tracking and analysis of water maze tests.
AB  - A crucial step in the estimation of properties of compounds in behavioral
      experiments is the quantification and description of the different effects
      observed. The goal of the present work was the automation of the Morris water
      maze test, one of the most popular behavioral methods for the study of animal
      memory. An original system was developed that provides fast and accurate tracking
      of animals, storage of the results in the database and video archive and a means
      of analyzing the results. This computerized version of the Morris water maze test
      permits the quantification of such vague characteristics of cognitive function as
      the "directionality" of search of the hidden platform after a standard training
      series. The suggested parameters made it possible to discriminate cognitive
      properties of the novel compounds from other behavioral effects affecting escape
      latency. The effectiveness of this system was demonstrated in two experiments
      with neurochemically lesioned and drug-treated rats.

PMID- 11591070
TI  - Robust tracking and posture description for laboratory rodents using active shape
      models.
AB  - We are in the process of developing an automated image analysis system, which
      uses deformable models of shape, learned from image examples, to interpret video
      images of rodents. Active shape models provide a compact description of the shape
      of the animal in a way that enables the postures the differentiate various
      behaviors to be distinguished. They also model the image profile across the shape
      boundary. We show how these features allow automatic, robust segmentation of the
      explicit object of interest. Rather than just detecting movement or changes from
      background in the image, the system can focus on objects that are of the correct
      shape and appearance. The modeling of the image profiles also allows the system
      to distinguish between the actual animal and image artifacts. We show how these
      techniques are being extended to extract postural information, which can then be
      integrated with positional data to produce a model of behavior.

PMID- 11591071
TI  - The modified hole board as a differential screen for behavior in rodents.
AB  - We describe a modified hole board (mHB) paradigm as a test for unconditioned
      behavior in rodents that is aimed at analyzing a variety of behavioral
      dimensions. We demonstrate that the mHB enables the investigation of different
      behavioral dimensions in rodents in only one test by reproducing the behavioral
      characteristics previously collected from multiple behavioral tests in rats bred
      for either high or low anxiety-related behavior. In addition, the test design,
      which allows the experimental animal to maintain social contact with its group
      mates during the test, was shown to minimize stress for experimental animals and,
      moreover, to enable the investigator to assess social affinity among group mates.
      In summary, the mHB test enables animal models to be comprehensively phenotyped,
      while simultaneously reducing the number of animals and the amount of time
      required. Therefore, the mHB represents an alternative to the common practice of
      using a series of more specific tests.

PMID- 11591072
TI  - EthoVision: a versatile video tracking system for automation of behavioral
      experiments.
AB  - The need for automating behavioral observations and the evolution of systems
      developed for that purpose is outlined. Video tracking systems enable researchers
      to study behavior in a reliable and consistent way and over longer time periods
      than if they were using manual recording. To overcome limitations of currently
      available systems, we have designed EthoVision, an integrated system for
      automatic recording of activity, movement, and interactions of animals. The
      EthoVision software is presented, highlighting some key features that separate
      EthoVision from other systems: easy file management, independent variable
      definition, flexible arena and zone design, several methods of data acquisition
      allowing identification and tracking of multiple animals in multiple arenas, and
      tools for visualization of the tracks and calculation of a range of analysis
      parameters. A review of studies using EthoVision is presented, demonstrating the
      system's use in a wide variety of applications. Possible future directions for
      development are discussed.

PMID- 11591073
TI  - Digital measurement of operant disk press force maintained in CD-1, BALB/c, and
      C57BL/6 mice.
AB  - Force of disk press responses by inbred (C57BL/6 and BALB/c) and outbred (CD-1)
      mice were measured with a PC/DOS-based system, which allowed for continuous
      measurement of pressing, as well as for control of reinforcer presentation on the
      basis of response-force dimensions. Photobeam-based measurement of mouse entry
      into a hopper where reinforcers were presented provided additional information
      about anticipatory and consumatory behavior in relation to environmental stimuli
      leading up to reinforcer delivery. Disk pressing was generated and measured with
      the use of an analog-to-digital interface with all three mouse strains. The
      strains differed in the physical and temporal characteristics of the disk press,
      as well as in the behavioral chain leading to reinforcer presentation. These
      measurement methods appear well suited for quantitating functional behavioral
      differences occasioned by genetic variations in mice.

PMID- 11591074
TI  - Ground reaction force and spatiotemporal measurements of the gait of the mouse.
AB  - Measurement of ground reaction forces with force plates permits quantification of
      the subtle changes in movement associated with a variety of pathophysiological
      states. The apparatus used here permits simultaneous recording of other spatial
      and temporal characteristics of gait. Since the mouse is becoming increasingly
      important for modeling human disorders, we have recorded ground reaction forces
      (P) in this species. To date, we have measured the vertical component (Pz) and
      found it to be similar to that of other species, in that a greater Pz is exerted
      via the forelimb, although the areas under the force/time curves, are not
      different. Different points of discontinuity are seen in the forelimb and
      hindlimb curves, indicating differential deployment. Pz varies consistently with
      stance time and is consistent across the adult life of the mouse. It is suggested
      that the technique has potential for the study of a variety of mouse models of
      disease and of their therapies.

PMID- 11591075
TI  - The use of operant technology to measure behavioral priorities in captive
      animals.
AB  - Addressing the behavioral priorities of captive animals and the development of
      practical, objective measures of the value of environmental resources is a
      principal objective of animal welfare science. In theory, consumer demand
      approaches derived from human microeconomics should provide valid measures of the
      value of environmental resources. In practice, however, a number of empirical and
      theoretical problems have rendered these measures difficult to interpret in
      studies with animals. A common approach has been to impose a cost on access to
      resources and to use time with each resource as a measure of consumption to
      construct demand curves. This can be recorded easily by automatic means, but in a
      number of studies, it has been found that animals compensate for increased cost
      of access with longer visit time. Furthermore, direct observation of the test
      animals' behavior has shown that resource interaction is more intense once the
      animals have overcome higher costs. As a consequence, measures based on time with
      the resource may underestimate resource consumption at higher access costs, and
      demand curves derived from these measures may not be a true reflection of the
      value of different resources. An alternative approach to demand curves is
      reservation price, which is the maximum price individual animals are prepared to
      pay to gain access to resources. In studies using this approach, farmed mink
      (Mustela vison) paid higher prices for food and swimming water than for resources
      such as tunnels, water bowls, pet toys, and empty compartments. This indicates
      that the mink placed a higher value on food and swimming water than on other
      resources.

PMID- 11591076
TI  - A multiple species approach to sequential learning: are you a man or a mouse?
AB  - We have developed a method for studying list learning in animals and humans, and
      we use variants of the task to examine list learning in rats, mice, and humans.
      This method holds several advantages over other methods. It has been found to be
      easily learned without lengthy pretraining. The data gathered with this procedure
      provide a measure of correct response rates, of incorrect responses and the
      locations of these responses, and of response latency on a trial-by-trial basis.
      We have examined mouse, rat, and human list acquisition of patterns ranging from
      12 to 48 items in length. This procedure has also been used to examine many
      aspects of list learning, such as the effects of the placement of phrasing cues
      that are either consistent or inconsistent with the structure of the list in rats
      and mice, the effects of phrasing cues of differing modalities in mice, the
      sensitivity of subjects to violations of list structure in rats, subjects'
      abilities to "chunk" from nonadjacent serial positions in structured lists in
      rats, and subjects' sensitivity to serial patterns with multiple levels of
      hierarchical organization. The procedure has also been used to examine the
      effects of drugs on sequential learning.

PMID- 11591077
TI  - Deaths: final data for 1999.
AB  - OBJECTIVES: This report presents final 1999 data on U.S. deaths and death rates
      according to demographic and medical characteristics. Trends and patterns in
      general mortality, life expectancy, and infant and maternal mortality are also
      described. A previous report presented preliminary mortality data for 1999.
      METHODS: In 1999 a total of 2,391,399 deaths were reported in the United States.
      This report presents tabulations of information reported on the death
      certificates completed by funeral directors, attending physicians, medical
      examiners, and coroners. Original records are filed in the State registration
      offices. Statistical information is compiled into a national data base through
      the Vital Statistics Cooperative Program of the National Center for Health
      Statistics (NCHS), Centers for Disease Control and Prevention. For the first time
      in a final mortality data report, age-adjusted death rates are based upon the
      year 2000 population and causes of death are processed in accordance with the
      Tenth Revision of the International Classification of Diseases (ICD-10). RESULTS:
      The 1999 age-adjusted death rate for the United States was 881.9 deaths per
      100,000 standard population, a 0.7 percent increase from the 1998 rate, and life
      expectancy at birth remained the same at 76.7 years. For all causes of death, age
      specific death rates rose for those 45-54 years, 75-84 years, and 85 years and
      over and declined for a number of age groups including those 5-14 years, 55-64
      years, and 65-74 years. Aortic aneurysm and dissection made its debut in the list
      of leading causes of death and atherosclerosis exited from the list. Heart
      disease and cancer continued to be the leading and second leading causes of
      death. The age-adjusted death rate for firearm injuries decreased for the sixth
      consecutive year, declining 6.2 percent between 1998 and 1999. The infant
      mortality rate, 7.1 infant deaths per 1,000 live births, was not statistically
      different from the rate in 1998. CONCLUSIONS: Generally, mortality continued long
      term trends. Life expectancy in 1999 was unchanged from 1998 despite a slight
      increase in the age-adjusted death rate from the record low achieved in 1998.
      Although statistically unchanged from 1998, the trend in infant mortality has
      been of a steady but slowing decline. Some mortality measures for women and
      persons 85 years and over worsened between 1998 and 1999.

PMID- 11591078
TI  - Hypnotic intervention for ambiguity as a depressive risk factor.
AB  - In the face of ambiguous life events, depressed individuals are more likely to
      make negative and depressing interpretations than nondepressed individuals.
      Fundamental to the success of cognitive-behavioral treatments, one of the most
      empirically supported treatments for depression is teaching the client to
      recognize and self-correct so-called cognitive distortions. To facilitate that
      learning process, clients can learn to better recognize and tolerate ambiguity
      inherent in many situations, and thereby diminish the drive to form subjective
      interpretations (either negative or positive) when more objective evidence is
      unavailable. This article describes ambiguity as a risk factor for depression and
      details a strategy employing hypnosis for teaching the skills of both recognizing
      and tolerating ambiguity.

PMID- 11591079
TI  - The use of a skill-based activity in therapeutic induction.
AB  - This paper describes a hypnotherapeutic intervention for a brain damaged 36-year
      old male who has suffered from asthma since infancy and seizure disorder from the
      age of eight. In early sessions it was discovered that conventional "passive
      relaxation" induction techniques seemed to exacerbate certain disturbing somatic
      experiences, which he refers to as scary feelings. It was found that his
      performance of a previously learned skilled activity (the playing of the computer
      game Tetris) permitted the experience of a highly focused but relaxed state that
      was conducive to therapeutic interaction. This approach to induction bears
      similarity to "active-alert" procedures but may be more importantly related to
      Mihaly Csikszentmihalyi's principle of flow, in that it involves engagement in a
      subjectively meaningful, skill-based activity.

PMID- 11591080
TI  - EEG P300 event-related markers of hypnosis.
AB  - Barabasz, Barabasz, Jensen, Calvin, Trevisan, and Warner (1999) showed that, when
      subjects are stringently selected for hypnotizability and responses are time
      locked to events, robust markers of hypnotic responding emerge that reflect
      alterations in consciousness that correspond to subjects' subjective experiences
      of perceptual alteration. To further test the Barabasz et al. (1999) hypothesis,
      we obtained EEG visual P300 event-related potentials (ERPs) from 20 high- and low
      hypnotizable subjects. The effects of positive obstructive and negative
      obliterating instructions were tested during waking and alert hypnotic
      conditions. High-hypnotizables showed greater ERP amplitudes in response to the
      negative hallucination condition and lower ERP amplitudes in response to the
      positive obstructive hallucination when compared to the low-hypnotizables.
      Contrary to socio-psychological or role play conceptualizations, the hypnotic
      induction resulted in specific psychophysiological responses which could not be
      produced by waking imagination or by the lows who were trying to mimic hypnotic
      responding.

PMID- 11591081
TI  - Acupuncture and clinical hypnosis for facial and head and neck pain: a single
      crossover comparison.
AB  - Despite their long histories, acupuncture and hypnosis have only recently been
      acknowledged as valuable by the medical establishment in the U.S. Few studies
      have used rigorous prospective measurement to evaluate the individual or relative
      merits of hypnosis and acupuncture in specific clinical settings. In this study,
      25 patients with various head and neck pain were studied. Each had an initial
      assessment of their pain, as well as of their attitudes and expectations. All
      patients received acupuncture, followed by a reassessment of their pain. After a
      washout period they received another assessment of pain before and after hypnosis
      therapy. Preferences for therapy were sought following the hypnotic intervention.
      Both acupuncture and hypnosis were effective at relieving pain under these
      conditions. The average relief in pain reported was 4.2 units on a ten point
      scale, with hypnosis reducing pain by a mean of 4.8 units, compared to 3.7 for
      acupuncture (p = 0.26). Patient characteristics appeared to impact the
      effectiveness of treatment: patients with acute pain benefited most from
      acupuncture treatment, whereas patients with psychogenic pain were more likely to
      benefit from hypnosis. Patients with chronic pain had more variation in their
      results. Patients who received healing suggestions from a tape during a hypnotic
      trance benefited more than those who received no such suggestion, and acupuncture
      patients who were needle phobic benefited less than those who were not fearful of
      needles. This study demonstrates the benefits of well designed studies of the
      effectiveness of these alternative modalities. More work is needed to help
      practitioners identify which patients are most likely to benefit from these
      complementary therapies.

PMID- 11591082
TI  - Hypnotic devices may be more than placebo.
AB  - The study attempted to assess the effectiveness of two devices in facilitating
      the induction of hypnosis in subjects preselected as low in hypnotizability.
      Undergraduates were exposed to no treatment (control) or one of four combinations
      of devices during the induction phase of being administered the Stanford Hypnotic
      Susceptibility Scale, Form B of Weitzenhoffer and Hilgard (1959). Analyses
      revealed only one of the conditions resulted in a significant difference in
      subjects' realness ratings of hypnotic items and an increase in hypnotizability
      score. If the effect is more than a chance significance of placebo, the
      underlying mechanisms remain unknown.

PMID- 11591083
TI  - For the record: a commentary on the role of suggestion in hypnosis.

PMID- 11591084
TI  - Mind, brain, and depression.

PMID- 11591085
TI  - Hypnosis in treating symptoms and risk factors of major depression.
AB  - This article summarizes aspects of effective psychotherapy for major depression
      and describes how hypnosis can further enhance therapeutic effectiveness.
      Hypnosis is helpful in reducing common symptoms of major depression such as
      agitation and rumination and thereby may decrease a client' sense of helplessness
      and hopelessness. Hypnosis is also effective in facilitating the learning of new
      skills, a core component of all empirically supported treatments for major
      depression. The acquisition of such skills has also been shown to not only reduce
      depression, but also the likelihood of relapses, thus simultaneously addressing
      issues of risk factors and prevention.

PMID- 11591086
TI  - What do we publish?

PMID- 11591087
TI  - Changes in quality of life following admission to palliative care units.
AB  - The primary goal of palliative care is to improve the quality of life (QOL) of
      people with a terminal illness. Previous studies of the impact of
      hospice/palliative care have documented improvement in physical and psychological
      symptoms, but not in overall QOL, due in part to the difficulties of measuring
      QOL. The McGill Quality of Life Questionnaire (MQOL) was developed to assess QOL
      in persons with advanced illness. MQOL scores were determined on admission and 7
      8 days later for sequential eligible and willing patients admitted to five
      palliative care units. These 88 patients represented 8% of those admitted to the
      units during the study period. Following the final MQOL completion, patients were
      interviewed and asked to describe the nature of the changes in QOL they had
      experienced since admission. Significant improvements were found in the MQOL
      total score and subscale scores reflecting physical, psychological and
      existential well-being. In the interviews patients indicated that they had
      experienced changes in physical, emotional and interpersonal status, in spiritual
      outlook, and in their preparation for death. They also described the impact of
      the palliative care unit environment. This is the first study to demonstrate that
      hospice/palliative care can improve existential well-being in addition to
      psychological and physical symptoms. It provides evidence in the patients' own
      words that improvements in QOL go beyond symptom control following admission to a
      palliative care unit. However, the study results are generalizable only to those
      few patients admitted who are well enough to complete a questionnaire 1 week
      after admission.

PMID- 11591088
TI  - Attitudes towards death and dying in a representative sample of the Italian
      population.
AB  - This study investigated attitudes in Italy towards incurable disease, death and
      dying, and analyses the answers given to questions regarding the end of life and
      the care of the terminally ill patient. Of 1011 people invited to take part in
      this study, 829 (82%) agreed to participate. People were interviewed about the
      images associated with death (47% of those interviewed associated death with
      cancer); telling the truth to the dying patient (13% were in favour of being made
      aware of their impending death); the place of death (62% preferred home, 7%
      hospital); the attitudes of the carers (38% affirmed that pain should be
      alleviated, without considering the length of life, while 8% stated that they
      would be prepared to bear physical suffering if it meant prolongation of life)
      and religious faith (88% of those interviewed declared themselves Christian).
      Comparing our data with a previous survey, carried out in 1988, we conclude that
      only small changes have occurred in attitudes in the intervening 11 years: a
      slight increase in those who said that they think 'often' or 'sometimes' about
      death (53% in 1999, 44% in 1988) and an increase in the number of people who
      associate the causes of death with cancer (47% in 1999, 36% in 1988). The fear
      has diminished of AIDS (5% versus 8%) and war (5% versus 12%) as causes of death.
      It is concluded that such studies will serve not simply to provide indicators of
      public tendencies or public interest in the problem, but will constitute a tool
      whereby those attitudes which merit close observation can be identified and,
      where necessary, changed.

PMID- 11591089
TI  - Receiving a diagnosis of lung cancer: patients' interpretations, perceptions and
      perspectives.
AB  - Lung cancer has a higher incidence than any other type of cancer and more than
      80% of sufferers die within a year of diagnosis. An important aspect of caring
      for cancer patients is the breaking of bad news, something that most doctors
      admit to having difficulty with. Only a few publications on this issue adopt the
      patients' perspective. This study aimed to document patients' views on delivery
      of lung cancer diagnoses, their attitudes to methods used and ideas for
      improvement. Patients were selected from medical, surgical and general
      practitioner clinics to provide insight into patients' perceptions of care in
      different environments. Those who gave informed consent completed a taped semi
      structured interview. Transcripts were analysed qualitatively using a
      phenomenological approach. Recruitment was stopped when saturation was reached:
      no new themes were being identified. A summary of results was sent to patients,
      whenever possible, for their comment. An independent researcher coded four
      transcripts to establish the degree of inter-rater reliability. Thirteen patients
      were recruited. There were five key areas: communication (including the use of
      words such as 'tumour' and 'growth'), family/community issues, reaction to
      diagnosis, views on treatment and prognosis (all of which were very variable),
      and suggested improvements (e.g. a clearer explanation of the experience of
      bronchoscopy in the patient information leaflet, PIL). Inter-rater reliability
      was good. The PIL is being revised. Factors including family situation and
      personal experience of illness vary greatly and yet they influence patients'
      reactions to receiving a diagnosis of lung cancer, their interpretation of this
      and their attitudes to the illness and treatment. These findings underline the
      need to continue to develop lung cancer services that can provide quality care
      tailored to each patient.

PMID- 11591090
TI  - Cross-cultural validation of the McGill Quality of Life questionnaire in Hong
      Kong Chinese.
AB  - The main focus of palliative care services is to improve patients' quality of
      life (QOL). The potential value of assessment of QOL in palliative care is being
      increasingly recognized. The McGill Quality of Life questionnaire (MQOL) is
      designed specifically for palliative care patients, but its cross-cultural
      validity needs to be determined before it can be applied in populations of
      different cultures and ethnic groups. The cross-cultural validity of MQOL was
      investigated using a translated and modified version in Chinese--the MQOL-HK--in
      462 palliative care patients in Hong Kong. Results show that the MQOL-HK is
      acceptable, valid and reliable. There is good acceptability, construct validity,
      convergent and divergent validity, test-retest and inter-rater reliability. Our
      study confirms that QOL does have cross-culturally robust constructs. Principal
      components analysis shows that the domains of physical, psychological,
      existential and support are all relevant and applicable in Chinese culture.
      Multiple regression analysis reveals that existential domain is the most
      important domain in predicting overall QOL. 'Face', eating and sex are additional
      facets of QOL that also need to be considered. The worst physical symptom on
      admission is the item of QOL with the lowest score, which need more care and
      attention by palliative care workers. A cross-culturally validated QOL instrument
      cannot just help ensure an accurate evaluation of profile, determinants, and
      changes of QOL, but is also a valuable asset for future comparison and evaluation
      of palliative care services and interventions across the world.

PMID- 11591091
TI  - Needs assessment for palliative care: three projects compared.
AB  - Needs assessment remains an inexact yet evolving field of activity in palliative
      care. One reason for the variable quality of needs assessments in palliative care
      is the pragmatic orientation that comes from limited time and resources.
      Consequently a comprehensive approach to palliative care needs assessment is
      often not achieved. One route to its improvement lies in sharing experiences
      about techniques and methods in conducting needs assessment studies. In this
      paper we offer some thoughts on our own experience of conducting needs assessment
      for palliative care in three separate locations within a single English health
      region. We describe the context in which the projects were conducted; the
      background and origin of each study; the aims and methods used; the research
      process in each case; key findings; as well as the dissemination process and
      impact of the work. We show some of the different forms which palliative care
      needs assessment can take and conclude with some general principles intended to
      improve practice in this challenging area of health services research.

PMID- 11591092
TI  - Transdermal fentanyl for pain relief in a paediatric palliative care population.
AB  - This multicentre, observational study examined the efficacy of the therapeutic
      transdermal fentanyl system (TTS-fentanyl) in children requiring opioids for pain
      in life-threatening disease. Forty-one children receiving oral morphine (median
      dose 60 mg/day) transferred to transdermal fentanyl (median dose 25 micrograms/h
      according with the manufacturer's dose conversion guidelines). Twenty-six
      children completed the 15-day treatment phase, seven died due to disease
      progression and eight were withdrawn because of adverse events, inadequate
      analgesia or a change to parenteral opioids. After 15 days, the median fentanyl
      dose was 75 micrograms/h (range 25-250). No serious adverse events were
      attributed to fentanyl. There was a trend toward improved side-effects and
      convenience with fentanyl. Twenty-three of 26 parents (three missing) and 25 of
      26 investigators considered transdermal fentanyl to be better than previous
      treatment. For all records available (at 15 days or on withdrawal if earlier),
      75% (27/36) reported that fentanyl treatment was 'good' or 'very good'. The
      findings suggest that transdermal fentanyl is both effective and acceptable for
      children and their families.

PMID- 11591093
TI  - Palliative care for patients with non-malignant disease: will hospital physicians
      refer?
AB  - The objective of this research was to determine whether consultant physicians
      would consider referring patients with non-malignant disease to a specialist
      palliative care service, and if so, which patients they would refer. In addition,
      reasons for referral, expectations of the palliative care team and concerns about
      the extension of palliative care to non-malignant disease were examined. A postal
      questionnaire was sent to all 100 consultant physicians, including
      subspecialities, working in hospitals in south-east Wales, UK. Out of the 100
      questionnaires, 78 physicians responded, of whom 94% would consider referring
      patients with non-malignant disease to a specialist palliative care service. The
      physicians would be prepared to refer patients with a wide range of conditions,
      for a variety of reasons. Among the physicians surveyed there was a general
      enthusiasm for specialist palliative care services to be made available to
      patients with non-malignant disease. The most appropriate form of service was
      thought to be a system of shared care and responsibility and this was seen as a
      means of addressing concerns regarding the lack of disease-specific expertise
      within the palliative care team.

PMID- 11591094
TI  - Improved accuracy of physicians' survival prediction for terminally ill cancer
      patients using the Palliative Prognostic Index.
AB  - The Palliative Prognostic Index (PPI) has recently been developed for survival
      prediction in terminally ill cancer patients. To clarify whether physicians'
      clinical prediction of survival (CPS) can be improved using this objective
      assessment aid, two sequential prospective studies were performed on two
      independent series of hospice inpatients (n = 150 and 108). In the first study,
      the CPS was prospectively recorded by primary physicians on the basis of their
      clinical experiences. In the second study, physicians estimated patient prognoses
      with a reference to the PPI score. The cases where the differences between actual
      survival (AS) and CPS were 28 days or longer significantly decreased in the
      second study compared to the first study (42% vs 23%, P < 0.01). Also, the cases
      where AS was either twice longer or half shorter than CPS significantly declined
      (49% vs 37%, P = 0.050). As well, serious errors, defined as the cases where AS
      was either (a) 28 days and twice longer than CPS or (b) 28 days and half shorter
      than CPS, significantly decreased from 27% in the first study to 16% in the
      second study (P = 0.028). In conclusion, the PPI can contribute to improvement in
      physicians' ability to predict survival of terminally ill cancer patients.

PMID- 11591095
TI  - Moral problems in palliative care journals.
AB  - With the growth of palliative care services, interest in moral issues also seems
      to be growing. However, we need to know which moral issues are specific to
      palliative care. The first step in answering this is to consider the moral
      concerns raised and discussed by the palliative care community itself. This
      article presents a bibliographical analysis of moral problems, first by selecting
      the problems identified as moral problems in the leading palliative care
      journals, and then by classifying these into different types.

PMID- 11591096
TI  - The analysis of qualitative data: processes and pitfalls.

PMID- 11591097
TI  - The use of oxygen concentrators within a hospice setting.

PMID- 11591098
TI  - Successful cardiopulmonary resuscitation in a hospice.

PMID- 11591099
TI  - Methods for the detection of anti-neutrophil cytoplasmic antibodies.
      Recommendations for clinical use of ANCA serology and laboratory efforts to
      optimize the informative value of ANCA test results.

PMID- 11591100
TI  - Clinical aspects of primary vasculitis.

PMID- 11591101
TI  - Immunopathological aspects of systemic vasculitis.

PMID- 11591102
TI  - Clinical management and treatment of vasculitis.

PMID- 11591103
TI  - Cellular aspects of vasculitis--T cell-mediated aspects.

PMID- 11591104
TI  - Role of proteinase 3 in activation of endothelium.

PMID- 11591105
TI  - An experimental model of cryoglobulin-associated vasculitis in mice.

PMID- 11591106
TI  - Interface-mediated oscillatory phenomena.
AB  - Oscillatory transport processes which occur in the far from equilibrium region
      have assumed great significance from the viewpoint of science of complexity.
      Oscillatory phenomena in the chemical reaction systems have been subjected to
      intense investigations both from theoretical and experimental angles. In the
      present review an effort has been made to bring transport processes other than
      conventional chemical reactions into focus: transport processes mediated by solid
      liquid and liquid-liquid interfaces have been discussed. Transport through
      membranes including liquid membranes, liquid-liquid interfaces and the recently
      reported hydrodynamic oscillator have been covered. Applications of these systems
      in areas such as fabrication of sensors, phase transfer catalysis and, of course,
      the obvious biological action, e.g. excitation of biomembranes and tissues, have
      been reviewed. Theoretical frameworks proposed to rationalize the phenomena have
      also been critically reviewed.

PMID- 11591107
TI  - Properties of the amphiphilic films in mixed cationic/anionic vesicles: a
      comprehensive view from a literature analysis.
AB  - The so-called 'catanionic' vesicles are made from mixtures of cationic and
      anionic surfactants. They are attracting much interest because they form
      spontaneously and they can be obtained from a variety of surfactants, either
      commercially available or issued from original synthesis. A distinction can be
      made between the properties of simple surfactant mixtures and of ion pair
      amphiphiles (IPA), in which the counterions have been removed. We have drawn up
      in this paper, an inventory of the different vesicular systems which have been
      described in the literature, insisting on the specific features associated with
      these two categories of systems. We have collected here especially, information
      concerning the phase behaviors, the microscopic composition of the vesicular
      particles, their structural and size determinations, the dynamic aspects
      (including the micelle-vesicle transition), the theoretical predictions from
      thermodynamic models and the entrapment of probe molecules. We discuss the
      potential of catanionic vesicles as delivery systems and we show that a full
      understanding of their entrapment/release properties will call for much more
      experimental work with well defined protocols. We also point out some unsolved
      questions concerning the role of the excess surfactant in the stabilization of
      the particles and the conditions required to obtain a favourable curvature of the
      surfactant film.

PMID- 11591108
TI  - Adsorption--from theory to practice.
AB  - Adsorption at various interfaces has concerned scientists since the beginning of
      this century. This phenomenon underlies a number of extremely important processes
      of utilitarian significance. The technological, environmental and biological
      importance of adsorption can never be in doubt. Its practical applications in
      industry and environmental protection are of paramount importance. The adsorption
      of substrates is the first stage in many catalytic processes. The methods for
      separation of mixtures on a laboratory and on an industrial scale are
      increasingly based on utilising the change in concentration of components at the
      interface. Moreover, such vital problems as purification of water, sewages, air
      and soil are involved here too. On the other hand, many areas in which
      technological innovation has covered adsorption phenomena have been expanded more
      through art and craft than through science. A basic understanding of the
      scientific principles is far behind; in part because the study of interfaces
      requires extremely careful experimentation if meaningful and reproducible results
      are to be obtained. In recent years, however, considerable effort has been
      increasingly directed toward closing the gap between theory and practice. Crucial
      progress in theoretical description of the adsorption has been achieved, mainly
      through the development of new theoretical approaches formulated on a molecular
      level, by means of computer simulation methods and owing to new techniques which
      examine surface layers or interfacial regions. Moreover, during the last 15 years
      new classes of solid adsorbents have been developed, such as activated carbon
      fibres and carbon molecular sieves, fullerenes and heterofullerenes, microporous
      glasses and nanoporous--both carbonaceous and inorganic--materials.
      Nanostructured solids are very popular in science and technology and have gained
      extreme interest due to their sorption, catalytic, magnetic, optical and thermal
      properties. Although the development of adsorption up to the 1918s has been
      following rather a zig-zag path, this arm of surface science is now generally
      considered to have become a well-defined branch of physical science representing
      an intrinsically interdisciplinary area between chemistry, physics, biology and
      engineering. This review presents in brief the history of adsorption and
      highlights the progress in theoretical description of the phenomenon under
      consideration. The paper deals with the above problems critically, showing the
      development of adsorption, presenting some of the latest important results and
      giving a source of up-to-date literature on it. Moreover, in this paper the most
      important aspects are overviewed referring to today's trends and visions in
      application of adsorption science in industry, environmental protection and in
      environmental analysis. The relationship between development of adsorption theory
      and adsorption practice is pointed out. Current understanding and perspectives
      pertaining to applications of adsorption phenomena on laboratory and on
      industrial scale as well as environmental protection are discussed and
      illustrated by means of a few spectacular examples.

PMID- 11591109
TI  - Steady shear rate rheology of suspensions, as described by the giant floc model.
AB  - The break-down of a particle network by shear is described as the development of
      shear planes: a region able to withstand low shear stresses may break down under
      a larger stress; thus with increasing shear stress and shear rate, the mutual
      distance (A) between successive shear planes decreases until, at very high shear
      rates, A approaches the particle diameter. The shear planes are idealised as flat
      planes. Energy dissipation during shear is predominantly due to the energy
      dissipated through the movement of the particles; the energy dissipation due to
      breakage and renewed formation of bonds between particles is relatively small. A
      consideration of the energy dissipated during the encounters of particles during
      shear, including that dissipated by entrained particles, then leads to a relation
      between this energy dissipation and the average fraction L, over which a moving
      particle entrains a neighbour. L includes the effect of parts of the network
      which are rotating under the influence of the shear. In the limit of large shear
      rates, L is found to depend only to a small extent on whether the suspension is
      coagulated or not.

PMID- 11591110
TI  - At the solid/liquid interface: FTIR/ATR--the tool of choice.
AB  - For the last 7 years, we have been researching various aspects of the Bayer
      process. Predominant among these has been the surface chemistry of Bayer process
      solids. To this end, we have been using Fourier transform infrared (FTIR)
      attenuated total reflection (ATR) spectroscopy for in situ studies of the
      surfaces of the Bayer process solids sodium oxalate and aluminium trihydroxide
      under extreme (high ionic strength, high pH), Bayer-like conditions. FTIR/ATR is
      one of the few techniques currently available to scientists wishing to explore
      solid/liquid interfacial phenomena in situ. Using this investigative technique,
      information regarding the nature of adsorbed species can be readily acquired,
      with details concerning adsorbate orientation and adsorption/desorption
      equilibria, speciation, mechanisms and kinetics obtainable. Not surprisingly,
      FTIR/ATR has become one of the tools of choice for those wishing to explore the
      solid/liquid interface, and the body of literature available on the subject has
      been steadily growing over the last 10-15 years. This review addresses the
      current state of knowledge in the area of FTIR/ATR with respect to interfacial
      spectroscopy, as well as introducing some of the more fundamental theoretical and
      practical aspects of the technique. Particular emphasis is placed upon applied
      interfacial research. In writing this review, we draw on a considerable amount of
      expertise in the use of FTIR/ATR in interfacial studies (in particular, the
      practical considerations involved), as well as a large and comprehensive
      literature database focussing primarily on the investigation of interfacial
      processes using the FTIR/ATR technique.

PMID- 11591111
TI  - CD antigens 2001.

PMID- 11591112
TI  - Requirement for sustained MAPK signaling in both CD4 and CD8 lineage commitment:
      a threshold model.
AB  - Although there is general agreement that the RAS/MAPK signaling pathway is
      required for positive selection of CD4 T cells in the thymus, the role of this
      pathway in CD8 lineage commitment remains controversial. We show here that the
      differentiation of isolated cultured thymocytes to the CD8 as well as CD4 T cell
      lineage is sensitive to MEK inhibition and that both CD4 and CD8 thymocyte
      differentiation requires sustained MEK signaling. However, CD4 lineage commitment
      is promoted by a stronger stimulus for longer duration than required for CD8
      lineage commitment. Interestingly, CD4 lineage commitment is not irreversibly set
      even after 10 h of signaling, well past early changes in gene expression. These
      findings are presented in the context of a model of lineage commitment in which a
      default pathway of CD8 lineage commitment is altered to CD4 commitment if the
      thymocyte achieves a threshold level of active MAPK within a certain time frame.

PMID- 11591113
TI  - Resistance to malarial infection is achieved by the cooperation of NK1.1(+) and
      NK1.1(-) subsets of intermediate TCR cells which are constituents of innate
      immunity.
AB  - We previously reported that the major expanding lymphocytes were intermediate TCR
      (TCR(int)) cells (mainly NK1.1(-)) during malarial infection in mice. Cell
      transfer experiments of TCR(int) cells indicated that these T cells mediated
      resistance to malaria. However, TCR(int) cells always contain NK1.1(+)TCR(int)
      cells (i.e., NKT cells) and controversial results (NKT cells were effective or
      not for resistance to malaria) have been reported by different investigators. In
      this study, we used CD1d((-/-)) mice, which almost completely lack NKT cells in
      the liver and other immune organs. Parasitemia was prolonged in the blood of
      CD1d((-/-)) mice and the expansion of lymphocytes in the liver of these mice was
      more prominent after an injection of Plasmodium yoelii-infected erythrocytes.
      However, these mice finally recovered from malaria. In contrast to B6 mice, CD4(
      )8(-) NKT cells as well as NK1.1(-)CD3(int) cells expanded in CD1d((-/-)) mice
      after malarial infection, instead of CD4(+) (and CD8(+)) NKT cells. These newly
      generated CD4(-)8(-)NKT cells in CD1d((-/-)) mice did not use an invariant chain
      of Valpha14Jalpha281 for TCRalpha. Other evidence was that severe thymic atrophy
      and autoantibody production were accompanied by malarial infection, irrespective
      of the mice used. These results suggest that both NK1.1(-) and NK1.1(+) subsets
      of TCR(int) cells (i.e., constituents of innate immunity) are associated with
      resistance to malaria and that an autoimmune-like state is induced during
      malarial infection.

PMID- 11591114
TI  - IL-1beta is essential for langerhans cell activation and antigen delivery to the
      lymph nodes during contact sensitization: evidence for a dermal source of IL
      1beta.
AB  - IL-1beta(-/-) mice manifest an impaired contact hypersensitivity response to the
      hapten trinitrochlorobenzene, with the principle defect expressed during the
      sensitization phase of this response. Following application of hapten to the
      skin, epidermal Langerhans cells of IL-1beta(-/-) mice failed to demonstrate the
      classical phenotype of activation. In addition, the delivery of epicutaneously
      applied fluorescein isothiocyanate to draining lymph nodes was decreased in IL
      1beta(-/-) mice. Hapten delivery to draining lymph nodes could be restored by
      intradermal injection of recombinant IL-1beta. Reconstitution of lethally
      irradiated IL-1beta(-/-) mice by transfer of wild-type bone marrow restored
      hapten-stimulated IL-1beta mRNA expression, demonstrating that IL-1beta
      production was dependent on bone marrow-derived cells. In wild-type skin, IL
      1beta expression was upregulated in a time- and dose-dependent fashion following
      hapten application. Interestingly, prominent IL-1beta expressing cells were found
      in the dermis, suggesting that dermal cells may contribute significantly to the
      contact hypersensitivity response.

PMID- 11591115
TI  - Roles of intracellular calcium and NF-kappaB in the Bacillus Calmette-Guerin
      induced secretion of interleukin-8 from human monocytes.
AB  - Interleukin (IL)-8 secretion contributes to the early host response against
      mycobacterial infection by increasing local inflammation and recruiting
      professional phagocytes. Because the mechanisms through which Mycobacterium bovis
      Calmette-Guerin (BCG) induces IL-8 secretion are unknown, the aim of the present
      study was to characterize the nature of IL-8 production induced by BCG in human
      monocytes. In this study, we found that the induction of IL-8 synthesis was dose-
      and time-dependent after stimulation with BCG. This IL-8 secretion was not
      attributed to LPS contamination or the presence of TNF-alpha. We also determined
      that BCG-induced IL-8 secretion occurs through a mechanism that requires
      intracellular calcium and likely involves a calmodulin-sensitive step.
      Interestingly, BCG-induced secretion of IL-8 from human monocytes resulted from
      transcriptional up-regulation of the IL-8 gene. Moreover, we present evidence
      that BCG activates nuclear translocation of the transcription factor NF-kappaB,
      since pretreatment of monocytes with sulfasalazine, a inhibitor of NF-kappaB
      activity, blocked the ability of BCG to induce IL-8 secretion in a dose-dependent
      manner, producing 92.5% inhibition at a concentration of 2 mM. These results were
      further supported by the fact that treatment of cells with curcumin, another well
      described inhibitor of NF-kappaB activity with a different mechanism of action,
      significantly diminished the effect of BCG on IL-8 secretion. Together, these
      studies are the first to demonstrate that BCG-induced IL-8 secretion by human
      monocytes appears to be mediated by intracellular Ca(2+) and is NF-kappaB
      dependent and at the same time suggest that production of IL-8 in response to M.
      bovis BCG can contribute to the initial local and systemic inflammatory response
      in human tuberculosis.

PMID- 11591116
TI  - Class switch recombination signals induce lymphocyte-derived Spo11 expression and
      Spo11 antisense oligonucleotide inhibits class switching.
AB  - Recently, we showed that mouse Spo11 is induced in normal mu(+) B cells by class
      switch recombination (CSR) stimuli, by RT-PCR using primers based on the reported
      cDNA sequence of testis-derived Spo11 (test-Spo11) cDNA. In the present study, we
      first determined the cDNA sequence of lymphocyte-derived Spo11 (lym-Spo11). The
      5' upstream portion had an as yet unreported sequence but the remaining part from
      exons 2 to 12 and the subsequent 3'UTR was completely identical to that of test
      Spo11. RT-PCR analysis indicated that lymphocytes express lym-Spo11 but not test
      Spo11. Second, we showed that lym-Spo11 is strongly induced (above eightfold) in
      the IgA CSR system of LPS-stimulated mu(+)B cells in the presence of all-trans
      retinoic acid and IL-4. Finally, we examined whether lym-Spo11 antisense S
      oligonucleotide (AS) can inhibit CSR reactions in three in vitro CSR systems,
      IgA,IgG1, and IgE. Lym-Spo11 AS or the sense oligonucleotide was added to the
      cultures at the start, and total RNA was extracted after 4 days. IgA, IgG1, and
      IgE mRNAs (J(H)C(H)) and mature germline C(H) transcripts (I(H)C(H)) were
      quantitatively assayed by RT-PCR. AS inhibited J(H)C(H) expression dose
      dependently. In all three systems, the maximum inhibition by 20 microM AS was in
      the range of 60 to 90%. Interestingly, I(H)C(H) was also inhibited by AS to a
      similar extent as J(H)C(H). These results suggested that lym-Spo11 plays an
      important role in the initiation step of CSR.

PMID- 11591117
TI  - Differential effect of IL-4 and IL-13 on CD44 expression in the Burkitt's
      lymphoma B cell line BL30/B95-8 and in Epstein-Barr virus (EBV) transformed human
      B cells: loss of IL-13 receptors on Burkitt's lymphoma B cells.
AB  - IL-4 and IL-13, cytokines with similar biological effects may influence growth
      and progression of B-cell tumors through regulation of key cell surface molecules
      important in intercellular communications. In this study, we demonstrate that IL
      4 and IL-13 exhibited differential effects on CD23 and CD44 expression and
      binding to hyaluronan in BL30/B95-8, a Burkitt's lymphoma (BL), and MK3.31, an
      Epstein-Barr virus transformed normal human B cell line (B-LCL). Studies
      conducted to understand the molecular mechanisms underlying this differential
      effect show that IL-4 induced phosphorylation of JAK1, JAK3, and STAT6 in
      BL30/B95-8 cells and of JAK3 and STAT6 in MK 3.31 cells. In contrast, IL-13
      failed to induce the phosphorylation of JAK kinases or STAT6 proteins in these
      cell lines. The inability of BL30/B95-8 cells to respond to IL-13 was attributed
      to the loss of expression of IL-13R subunits alpha1 and alpha2, a finding
      confirmed for a number of other BL cell lines examined.

PMID- 11591118
TI  - Heterosubtypic immunity against human influenza A viruses, including recently
      emerged avian H5 and H9 viruses, induced by FLU-ISCOM vaccine in mice requires
      both cytotoxic T-lymphocyte and macrophage function.
AB  - Induction of heterosubtypic immunity to influenza viral antigens is of paramount
      importance to the prevention of epidemics and potential pandemics. The 1997
      incidence of avian influenza infections in humans in Hong Kong heightened the
      need for pandemic preparedness and a search for vaccines and vaccine delivery
      systems that can confer broad protection. In this report, we demonstrate that the
      delivery of H1N1 subtype influenza viral antigens as immunostimulating complexes
      (ISCOM) induces broad cross-protection in mice against challenge with various
      influenza virus subtypes, including the avian H9 and the H5 strains that were
      recently responsible for deaths in humans. The ISCOM delivery system induced high
      and long-lived serum antiviral antibodies and class I-restricted cytotoxic T
      lymphocytes (CTL). Studies with perforin, IFN-gamma, and mu-chain gene knock-out
      mice demonstrated that the heterosubtypic protection required cross-reactive,
      functional cytotoxic T cells and nonhemagglutination inhibiting serum antibodies.
      Interferon-gamma, a major player in viral clearance by nonlytic mechanisms, did
      not appear to play a role in heterosubtypic immunity. Nonformulated H1N1
      influenza antigens failed to induce significant CTL or long-lasting antibody
      responses or to protect mice against challenge with heterosubtypic viruses.
      Furthermore, while influenza virus infection induced a dominant nucleoprotein
      (NP)-specific CTL response in H2 mice, the ISCOM delivery system induced a
      dominant hemagglutinin-specific CTL response. Moreover, non-neutralizing but
      cross-reactive antibodies played a role in reducing viral titers by macrophages.
      These results suggest that exogenous delivery of influenza antigens as ISCOM can
      influence their antigen processing and presentation, their ability to
      induce/recall CTL specificities, and their capacity to mediate broad cross
      protection against influenza virus variants.

PMID- 11591119
TI  - Dominant role of intercellular adhesion molecule-1 in the pathogenesis of
      autoimmune diabetes in non-obese diabetic mice.
AB  - Intercellular adhesion molecule (ICAM)-1 is involved in forming the immunological
      synapse. The contribution of ICAM-1 to immune responses is not critical because
      mice with a disrupted ICAM-1 gene do not have grossly abnormal immune reactivity.
      Here we report on the surprising finding that diabetes-prone NOD mice with a
      disrupted ICAM-1 gene (ICAM-1(-/-)) are completely protected from disease
      development. While 64% of ICAM-1(+/+) and 44% of ICAM-1(+/-) female NOD mice
      developed overt diabetes until 310 days old, no ICAM-1(-/-) NOD mice became
      hyperglycaemic. Histological examinations revealed minor infiltration around
      pancreatic islets of ICAM1(-/-) NOD mice. Administration of cyclophosphamide
      caused a progression to severe islet destruction in ICAM-1(+/+) NOD mice within
      10 days. In contrast, ICAM-1(-/-) mice showed only mild insulitis. Furthermore,
      ICAM-1(+/+) NOD mice showed an increase of IFN-gamma, interleukin (IL)-12p40 and
      IL-12p35 pancreatic mRNA levels, leading to an increased ratio of IFN-gamma: IL-4
      and IL-12p40: IL-12p35 expression. In contrast, ICAM-1(-/-) NOD mice did not
      upregulate IFN-gamma or IL-12p40 gene expression but maintained IL-4 and
      increased IL-12p35 gene expression. These results identify a dominant and non
      redundant role of ICAM-1 in the development of autoimmune diabetes.

PMID- 11591120
TI  - Complete suppression of insulitis and diabetes in NOD mice lacking interferon
      regulatory factor-1.
AB  - Interferon regulatory factor-1 (IRF-1), a transcriptional factor, regulates type
      I interferon and interferon-induced genes. It was reported that IRF-1 regulates
      important molecules required for inflammation and immune reactions. To
      investigate the role of IRF-1 in the development of autoimmune diabetes, we
      established IRF-1 deficient (IRF-1(-/-)) non-obese diabetic (NOD) mice. IRF-1
      deficient C57BL/6J mice were out-crossed to NOD mice, and F1 were backcrossed to
      NOD mice. At the N8 generation, the heterozygote for IRF-1 mutation was
      intercrossed and N8F1 was obtained. Out of three NOD genotypes, IRF-1(+/+) and
      IRF-1(+/-) developed spontaneous diabetes with an incidence of 47% (9/19) and 50%
      (10/20) by 30 weeks of age, respectively; whereas IRF-1(-/-) did not develop
      diabetes (0/18, P< 0.01 vs. (+/+) and (+/-)). Histologically, IRF-1(+/+) and IRF
      1(+/-) had various degrees of insulitis, but IRF-1(-/-) had no insulitis. In
      comparison with IRF-1(+/+), the percentage of CD4(+) and Mac-1(+) splenic cells
      significantly increased, whereas CD3(+), CD8(+) and B220(+) cells decreased in
      IRF-1(-/-). Furthermore, spleen cell proliferation in response to Con A or murine
      GAD65 peptide, a major autoantigen of the pancreatic beta-cell, significantly
      increased, and the IFN-gamma/IL-10 ratio in the culture supernatant significantly
      decreased in IRF-1(-/-), suggesting Th2 deviation in cytokine balance. These
      results indicate that IRF-1 plays a key role in developing insulitis and diabetes
      in NOD mice.

PMID- 11591121
TI  - Systemic macrophage activation in locally-induced experimental arthritis.
AB  - Local and systemic macrophage activation was examined during the course of
      monoarticular murine antigen-induced arthritis (AIA), induced by systemic
      immunization and subsequent local induction. The levels of tumour necrosis factor
      alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-12p70, and nitric oxide
      (NO) were determined in joints, sera, and supernatants of peritoneal macrophages
      (the latter unstimulated or stimulated ex vivo with LPS/IFN-gamma). In comparison
      with normal mice, systemic immunization (day 0) was associated to significant
      rise of TNF-alpha in serum, IL-1beta in the joints, IL-6 in unstimulated
      macrophages and IL-12p70 in stimulated macrophages. Local induction led to a
      further significant increase of: (i) TNF-alpha, IL-1beta, and IL-6 in the joints;
      and (ii) IL-1beta, and IL-6 in sera and stimulated macrophages during acute
      and/or early chronic AIA (days 1 to 7). Unstimulated macrophages showed increased
      NO release (day 3), while stimulated macrophages significantly increased
      secretion of IL-12p70 (day 1). In late chronic AIA (day 21), cytokine/NO
      expression returned to immunization levels or below at all sites; solely IL-1beta
      in the joints remained significantly above normal levels. Therefore, the
      prevalently local AIA model is characterized by a mixture of local and systemic
      activation of the mononuclear phagocyte system (MPS). While systemic MPS
      activation preceding arthritis induction can be attributed to systemic
      immunization, further systemic activation during arthritis appears an integral
      pathogenetic component of AIA.

PMID- 11591122
TI  - A dinucleotide repeat polymorphism at the poly(ADP-ribose) polymerase gene is not
      associated with predisposition to type 1 diabetes in French Caucasians.
AB  - The poly (ADP-ribose) polymerase (PARP) is a nuclear enzyme that detects and
      binds DNA strand breaks. Excessive PARP activation leads to the death of mice
      islet beta-cells by depleting cellular energy reserves. On the other hand, PARP
      mutant mice are resistant to streptozotocine-induced diabetes, and in the non
      obese diabetic (NOD) mouse model, treatment with nicotinamide, a PARP inhibitor,
      protects islet cells against cytotoxic actions in vitro and results in a
      decreased incidence of type 1 diabetes. PARP gene in human is located within a
      recently identified type 1 diabetes-susceptibility region on chromosome 1q41-42,
      and contains a polymorphic CA dinucleotide repeat in the promoter region. To
      consider the putative involvement of PARP polymorphism in predisposition to type
      1 diabetes, we performed genotyping for the various alleles of the CA
      dinucleotide repeat in 158 unrelated French Caucasian patients with type 1
      diabetes and 193 ethnically-matched healthy controls. We found no significant
      difference of PARP alleles distribution between patients and controls, even after
      stratification of the patients according to HLA class II genotype or to age at
      disease onset. Our results suggest that this PARP polymorphism does not influence
      susceptibility to type 1 diabetes in French Caucasians.

PMID- 11591123
TI  - Induction of salivary gland epithelial cell injury in Sjogren's syndrome: in
      vitro assessment of T cell-derived cytokines and Fas protein expression.
AB  - Sjogren's syndrome (SS) is an exocrinopathy characterized by T cell infiltrates,
      salivary gland epithelial cell (SGEC) apoptosis and high Fas and FasL expression.
      To address the participation of T cell-derived cytokines and of Fas apoptotic
      pathway in SS glandular lesions, we utilized non-neoplastic SGEC lines
      established from SS patients and controls. Possibly attesting to their intrinsic
      activation, cell lines derived from SS patients displayed significantly higher
      constitutive Fas and FasL than controls. Surface co-expression of Fas and FasL
      was not associated with spontaneous fratricide apoptosis. SGEC were resistant to
      anti-Fas-mediated apoptosis (possibly owing to the constitutive expression of
      anti-apoptotic proteins cFLIP and Bcl-2), but became sensitive after protein or
      RNA synthesis inhibition. IFN-gamma and TNF-alpha were able to upregulate surface
      Fas and FasL, whereas IL-1beta downregulated surface FasL. IFN-gamma (but not
      several other cytokines) reduced the survival of SGEC in a dose- and time
      dependent manner and induced Fas/FasL-mediated apoptosis, directly and via
      anoikia. Dexamethasone inhibited the upregulation of Fas and FasL by IFN-gamma
      and the induction of SGEC apoptosis and detachment by anti-Fas mAb or IFN-gamma.
      Our findings indicate the injurious role of IFN-gamma for the salivary epithelia
      of SS patients through the induction of Fas-mediated apoptosis and anoikia.

PMID- 11591124
TI  - Quantitative and qualitative analysis of the balance between type 1 and type 2
      cytokine-producing CD8(-) and CD8(+) T cells in systemic lupus erythematosus.
AB  - The production of type 1 (IFN-gamma, IL-2) and type 2 (IL-4, IL-5, IL-10, IL-13)
      cytokines by CD8(-) and CD8(+) T cells from systemic lupus erythematosus (SLE)
      patients and normal subjects was investigated using an intracellular cytokine
      staining technique. This flow cytometric method facilitates analysis of both
      surface markers and cytoplasmic cytokines, after a short term (6 h) culture with
      or without phorbol myristate acetate and ionomycin (PMA/I) stimulation. In SLE
      patients, more unstimulated T cells produced IL-10 in comparison with controls;
      other cytokines were not detected in unstimulated cells. The percentage of IL-10
      secreting T cells did not significantly increase after PMA/I stimulation of cells
      from SLE patients. The mean intensity of fluorescence (MIF) of intracellular IL-4
      staining was significantly higher in CD8(-) T cells of SLE patients than
      controls. Significantly fewer CD8(-) and CD8(+) T cells from SLE patients
      secreted IFN-gamma after PMA/I stimulation compared with controls. The MIF and
      percentage of IL-2, IL-5, and IL-13-secreting cell subsets were not significantly
      different between SLE patients and controls. These findings indicate that T cells
      of SLE patients are already stimulated to produce IL-10 in vivo, which may result
      in downregulation of IFN-gamma secreting CD8(-) and CD8(+) T cells observed
      following PMA/I stimulation. Thus, the population size of Th1 and Tc1 cells are
      reduced in SLE patients whereas the effector function of Th2 cells, with respect
      to IL-4 production, is enhanced in SLE patients. Furthermore, although the
      balance between Th1/Th2 and between Tc1/Tc2 is disrupted in SLE patients, it is
      significantly biased in favour of the Th2 subset only.

PMID- 11591125
TI  - Autoantibodies to pancreatic hsp60 precede the development of glucose intolerance
      in patients with cystic fibrosis.
AB  - Persons expressing the genetic disease cystic fibrosis (CF) suffer from a high
      risk of developing impaired glucose tolerance and diabetes. The development of
      diabetes in CF has been attributed, in the past, to the destruction of pancreatic
      islets and their resident beta-cells secondary to the destruction of the
      surrounding tissue by mechanical clogging of the pancreatic exocrine ducts.
      However, the discovery that autoimmunity to the 60-kDa heat shock protein (hsp60)
      may cause type I diabetes in NOD mice raises the possibility that hsp60
      autoimmunity may be involved in CF diabetes too; could the hyperimmunization to
      bacterial hsp60 characteristic of CF spread to self-hsp60 and hence to autoimmune
      diabetes? We now report that rising levels of IgG autoantibodies to hsp60 do
      indeed precede the appearance of glucose intolerance and diabetes in CF patients.
      We produced a recombinant human pancreatic hsp60 protein and investigated the IgG
      antibody response to hsp60 in prediabetic and non-diabetic patients with CF. To
      detect hsp60 autoantibodies in the presence of high levels of antibodies to
      bacterial hsp60, we absorbed test sera with the 60-kDa GroEL of Pseudomonas
      aeruginosa and used an immunostaining technique. Using this technique, 32
      prediabetic CF patients were evaluated over a five-year period, three years, on
      the average, before the onset of glucose intolerance. We found that a significant
      increase in hsp60 autoantibody preceded impaired glucose tolerance (P=0.042,
      n=17), diabetes (P=0.011, n=15) and glucose intolerance (P=0.005, n=32). As has
      been observed in NOD mice and in type I diabetic patients, the hsp60
      autoantibodies decline at the outbreak of glucose intolerance in the CF patients.
      The association of CF diabetes with the rise and fall of hsp60 autoimmunity
      suggests that the pathogenesis of the diabetes may not be merely mechanical, but
      arise in the wake of bacterial hyperimmunisation.

PMID- 11591126
TI  - The neuroprotective agent memantine induces brain-derived neurotrophic factor and
      trkB receptor expression in rat brain.
AB  - Memantine is a medium-affinity uncompetitive N-methyl-d-aspartate receptor
      antagonist and has been clinically used as a neuroprotective agent to treat
      Alzheimer's and Parkinson's diseases. We have examined the effect of memantine
      (ip 5-50 mg/kg; 4 h) on the expression of brain-derived neurotrophic factor
      (BDNF) and trkB receptor mRNAs in rat brain by in situ hybridization. Memantine
      at a clinically relevant dose markedly increased BDNF mRNA levels in the limbic
      cortex, and this effect was more widespread and pronounced at higher doses.
      Effects of memantine on BDNF mRNA were also reflected in changes in BDNF protein
      levels. Moreover, memantine induced isoforms of the BDNF receptor trkB. Taken
      together, these data suggest that the neuroprotective properties of memantine
      could be mediated by the increased endogenous production of BDNF in the brain.
      These findings may open up new possibilities of pharmacologically regulating the
      expression of neurotrophic factors in the brain.

PMID- 11591127
TI  - Soluble myelin-associated glycoprotein released from damaged white matter
      inhibits axonal regeneration.
AB  - The adult, mammalian CNS does not regenerate after injury largely because of a
      glial scar and inhibitors of regeneration in myelin. To date, two myelin
      inhibitors, myelin-associated glycoprotein (MAG) and Nogo, both transmembrane
      proteins, have been identified. No secreted inhibitors of regeneration have been
      described. However, a proteolytic fragment of MAG (dMAG), consisting of the
      entire extracellular domain, is readily released from myelin and is found in
      vivo. Here, we show, first, that a soluble, chimeric form of MAG (MAG-Fc), when
      secreted from CHO cells in a collagen gel and hence in the absence of a fixed
      substrate, inhibits/deflects neurite outgrowth from P6 dorsal root ganglion (DRG)
      neurons. This inhibition was blocked when a MAG monoclonal antibody was included
      in the gel and a control chimera sialoadhesin-Fc (Sn-Fc), which, like MAG, binds
      neurons in a sialic acid-dependent manner but does not inhibit axonal growth, had
      no effect. Using the same assay system we showed that factors secreted from
      damaged white matter inhibited/deflected neurite outgrowth. This inhibition was
      neutralized when a MAG monoclonal antibody was included in the gel and there was
      no inhibition when white matter from a MAG knockout mouse was used. Factors
      secreted from damaged white matter from wild-type mice had no effect on neurite
      outgrowth from E18 DRG neurons. These results show that factors secreted from
      damaged white matter inhibit axonal regeneration and that the majority of
      inhibitory activity can be accounted for by dMAG. Thus, released dMAG is likely
      to play an important role in preventing regeneration, immediately after injury
      before the glial scar forms.

PMID- 11591128
TI  - Role of STAT3 and PI 3-kinase/Akt in mediating the survival actions of cytokines
      on sensory neurons.
AB  - The binding of cytokines to the gp130 receptor activates the STAT3, MEK/MAPK, and
      PI3K/Akt signalling pathways. To assess the relative importance of these pathways
      in promoting the survival of cytokine-dependent neurons, we conditionally
      inactivated STAT3 in mice and inhibited MEK, PI3K, and Akt in cultured neurons
      using pharmacological reagents and by expressing specific inhibitory proteins.
      Inactivation of STAT3 enhanced the death of the cytokine-dependent sensory
      neurons of the nodose ganglion in vivo and substantially reduced the response of
      these neurons to CNTF and LIF in vitro. LY294002, an inhibitor of PI3K, but not
      PD98059, an inhibitor of MEK, markedly reduced the response of these neurons to
      CNTF, as did dominant-negative PI3K, dominant-negative Akt, and overexpression of
      Ruk (a natural PI3K inhibitor). These results demonstrate that STAT3 and PI3K/Akt
      signalling play major roles in mediating the survival response of neurons to
      cytokines.

PMID- 11591129
TI  - Evidence for gradients of gene expression correlating with zonal topography of
      the olfactory sensory map.
AB  - Signals regulating diversification of olfactory sensory neurons to express
      odorant receptors and other genes necessary for correct assembly of the olfactory
      sensory map persist in the olfactory epithelium of adult mouse. We have screened
      for genes with an expression pattern correlating with the topography odorant
      receptor-expression zones. The Msx1 homeobox gene and a semaphorin receptor
      (Neuropilin-2) showed graded expression patterns in the olfactory epithelium. The
      gradients of Msx1 and Neuropilin-2 expression in basal cells and neurons,
      respectively, correlated with expression of a retinoic acid-synthesizing enzyme
      (RALDH2) in lamina propria. A BMP-type I receptor (Alk6) showed a reverse
      gradient of expression in the supporting cells of the epithelium. Considering
      known functions of identified genes in cell specification and axon guidance this
      suggests that zonal division of the olfactory sensory map is maintained, during
      continuous neurogenesis, as a consequence of topographic counter gradients of
      positional information.

PMID- 11591130
TI  - Characterization of a metabotropic glutamate receptor type 5-green fluorescent
      protein chimera (mGluR5-GFP): pharmacology, surface expression, and differential
      effects of Homer-1a and Homer-1c.
AB  - Metabotropic glutamate receptor 5 (mGluR5) can modulate synaptic transmission by
      increasing intracellular Ca2+ and it plays a role in several forms of synaptic
      plasticity. We have constructed a fusion of human mGluR5 and green fluorescent
      protein (mGluR5-GFP). Expression of mGluR5-GFP in clonal cell lines yielded a
      functional fluorescent receptor with pharmacological profiles similar to wild
      type mGluR5. mGluR5-GFP coimmunoprecipitated with Homer-1c, indicating that
      addition of GFP to the C-terminal did not prevent Homer binding. Coexpression of
      wild-type mGluR5 or mGluR5-GFP with Homer 1c, but not Homer-1a, resulted in
      reduced receptor surface localization and the formation of intracellular
      clusters. Neither Homer-1a nor Homer-1c had any effect on mGluR1 or mGluR1-GFP
      distribution. mGluR5-GFP expressed alone or in combination with Homer-1a formed
      dimers in HEK cells. Coexpression with Homer-1c, however, prevented mGluR5-GFP
      dimerization. Neither Homer altered the agonist profiles of mGluR5 or mGluR5-GFP.
      These data indicate that the functional expression of mGluR5 is regulated by
      Homer-1c and demonstrate that mGluR5-GFP provides a useful tool to study the
      molecular pharmacology and cell biology of mGluRs in real-time.

PMID- 11591131
TI  - Doublecortin interacts with mu subunits of clathrin adaptor complexes in the
      developing nervous system.
AB  - Doublecortin is a microtubule-associated protein required for normal
      corticogenesis in the developing brain. We carried out a yeast two-hybrid screen
      to identify interacting proteins. One of the isolated clones encodes the mu1
      subunit of the adaptor complex AP-1 involved in clathrin-dependent protein
      sorting. We found that Doublecortin also interacts in yeast with mu2 from the AP
      2 complex. Mutagenesis and pull-down experiments showed that these interactions
      were mediated through a tyrosine-based sorting signal (YLPL) in the C-terminal
      part of Doublecortin. The functional relevance of these interactions was
      suggested by the coimmunoprecipitation of Doublecortin with AP-1 and AP-2 from
      mouse brain extracts. This interaction was further supported by RNA in situ
      hybridization and immunofluorescence studies. Taken together these data indicate
      that a certain proportion of Doublecortin interacts with AP-1 and/or AP-2 in vivo
      and are consistent with a potential involvement of Doublecortin in protein
      sorting or vesicular trafficking.

PMID- 11591132
TI  - Analysis of the NF-kappa B and PI 3-kinase/Akt survival pathways in nerve growth
      factor-dependent neurons.
AB  - Nerve growth factor (NGF) readdition to NGF-deprived neurons can halt Jun N
      terminal kinase (JNK) activation, cytochrome c release, and cell death through
      mechanisms that may involve phosphatidylinositol (PI) 3-kinase, Akt, and nuclear
      factor kappa B (NF-kappaB). We found that expression of the NF-kappaB protein c
      Rel in NGF-deprived neurons blocks cytochrome c release but does not inhibit c
      Jun phosphorylation. Conversely, inhibition of NF-kappaB in NGF-maintained
      neurons promotes cytochrome c release and cell death. In contrast to c-Rel,
      activated PI 3-kinase and Akt inhibit c-Jun phosphorylation but have only a small
      effect on cytochrome c release. Finally, although c-Rel can protect neurons from
      death caused by inhibitors of PI 3-kinase or Akt, NF-kappaB function is not
      critical for Akt-promoted survival. These results suggest that the PI 3
      kinase/Akt and NF-kappaB survival pathways target distinct cell death events in
      neurons.

PMID- 11591133
TI  - Complete nucleotide sequence and characterization of pUA140, a cryptic plasmid
      from Streptococcus mutans.
AB  - Approximately 5% of strains of Streptococcus mutans contain plasmid DNA. Strain
      UA140 harbors a 5.6-kb cryptic plasmid, pUA140, with an overall G+C content of
      32.7%. Five open reading frames (ORF), encoding peptides of larger than 100 amino
      acid residues, were initially designated as ORF1 to ORF5. These five ORFs were
      located on the same strand of pUA140. ORF1 (258 amino acids) resembled a
      replication protein, Rep. Upstream of the putative Rep gene, a double-stranded
      origin for plasmid replication that showed strong similarity to those of a number
      of plasmids in the pT181 family was identified. Further upstream was a region
      constituting the single-stranded origin of replication. A single-stranded DNA
      intermediate was detected during plasmid replication. Taken together, these
      results suggest that pUA140 replicated by the rolling circle replication
      mechanism but exhibited several characteristics that differ from those of other
      members of the pT181 plasmid family.

PMID- 11591134
TI  - Nucleotide sequence, structural organization, and functional characterization of
      the small recombinant plasmid pOM1 that is specific for Francisella tularensis.
AB  - pOM1 is a recombinant 4442-bp plasmid that includes the replicon of the
      Francisella novicida-like strain F6168 cryptic plasmid pFNL10 and the
      tetracycline resistance gene (tetC) of plasmid pBR328. pOM1 can stably replicate
      and is maintained in Francisella tularensis biovars tularensis, palaearctica, and
      palaearctica var. japonica. The replicon of pOM1 includes the ori region and the
      repA gene. The ori region, located upstream of the repA gene includes two sets of
      31- and 13-bp direct repeats (DR), with AT-rich regions preceding each of the
      DRs. Two putative promoters of the repA gene were found connected with the DR
      regions. A 40-kDa protein was encoded by the repA gene and found essential for
      replication. Expression of the tetC gene is regulated by an Escherichia coli
      sigma(70)-like promoter and is dependent on the F. tularensis strain and its
      environment.

PMID- 11591135
TI  - Role of the double-strand origin cruciform in pT181 replication.
AB  - pT181 is a small rolling-circle plasmid from Staphylococcus aureus whose
      initiator protein, RepC, melts the plasmid's double-strand origin (DSO) and
      extrudes a cruciform involving IR II, a palindrome flanking the initiation nick
      site. We have hypothesized that the cruciform is required for initiation,
      providing a single-stranded region for the assembly of the replisome (R. Jin et
      al., 1997, EMBO J. 16, 4456-4566). In this study, we have tested the requirement
      for cruciform extrusion by disrupting the symmetry of the IR II palindrome or by
      increasing its length. The modified DSOs were tested for replication with RepC in
      trans. Rather surprisingly, disruption of the IR II symmetry had no detectable
      effect on replication or on competitivity of the modified DSO, though plasmids
      with IR II disrupted were less efficiently relaxed than the wild type by RepC.
      However, in conjunction with IR II disruption, modification of the tight RepC
      binding site IR III blocked replication. These results define two key elements of
      the pT181 initiation mechanism--the IR II conformation and the RepC binding site
      (IR III)--and they indicate that pT181 replication initiation is sufficiently
      robust to be able to compensate for significant modifications in the
      configuration of the DSO.

PMID- 11591136
TI  - Construction of compatible wide-host-range shuttle vectors for lactic acid
      bacteria and Escherichia coli.
AB  - A new collection of shuttle cloning vectors has been constructed that can be used
      in a broad host range, because they carry replication origins which are
      functional in Escherichia coli (p15A, pWV01, ColE1), Lactococcus lactis,
      lactobacilli, and Bacillus subtilis (pAMbeta1, pWV01). These plasmids contain the
      lacZ-T1T2 cassette from pJDC9, which allows the X-gal selection and cloning of
      DNA fragments that could cause plasmid instability in E. coli. In addition, they
      have been proved to be structurally and segregationally stable in Lactobacillus
      casei, in which their copy number has been determined by real-time quantitative
      PCR. Furthermore, the antibiotic resistance markers (beta-lactamase,
      chloramphenicol acetyl transferase, and erythromycin transacetylase) and the
      theta and rolling circle replicating origins have been combined to obtain this
      set of compatible plasmids (pIA family) that can be cotransformed, both in lactic
      acid bacteria and in E. coli.

PMID- 11591137
TI  - Completion of the nucleotide sequence of the Enterococcus faecalis conjugative
      virulence plasmid pAD1 and identification of a second transfer origin.
AB  - pAD1 is a 59.3-kb plasmid in Enterococcus faecalis that has been the subject of
      intense investigation with regard to its pheromone-inducible conjugation behavior
      as well as its contribution to virulence. Approximately two-thirds of the pAD1
      nucleotide sequence has been previously reported. Here we report on an analysis
      of the final approximately 22 kb, a significant portion of which is believed to
      encode structural genes associated with conjugation. The conjugation-related
      region was also found to contain a new (second) origin of conjugative transfer
      (oriT). A list of open reading frames covering the entire plasmid is presented.

PMID- 11591138
TI  - Characterization of pEC156, a ColE1-type plasmid from Escherichia coli E1585-68
      that carries genes of the EcoVIII restriction-modification system.
AB  - The complete 4312-bp sequence of the pEC156 plasmid from Escherichia coli E1585
      68, which carries genes encoding the EcoVIII restriction-modification (R-M)
      system, an isoschizomer of HindIII from Haemophilus influenzae, has been
      determined. Two clustered and convergently oriented open reading frames, large
      enough to encode genes of the EcoVIII R-M system, were found. The transcriptional
      start points were mapped by the primer extension method. The relative molecular
      masses of the EcoVIII endonuclease and EcoVIII methyltransferase deduced from the
      nucleotide sequence are 35,554 and 33,910, respectively. Nucleotide sequence
      analysis of pEC156 suggests that this plasmid is a ColE1-type replicon. It
      consists of an origin of replication and two untranslated genes encoding RNA I
      and RNA II, both involved in the regulation of plasmid DNA replication. The
      replication region also contains the gene encoding a 64-aa Rom-like protein.
      Inactivation of the putative rom gene by insertion of a kanamycin-resistance
      cassette resulted in 4.5-fold increase in pEC156-derived plasmid copy number in
      E. coli cells. All of these elements (RNA I, RNA II, and rom) reveal a high level
      of similarity to ColE1 homologs. The replication of all ColE1-type plasmids is
      dependent on the activity of E. coli DNA polymerase I. It was shown that a pEC156
      derivative (pIB8) carrying an antibiotic resistance gene indeed failed to
      replicate in an E. coli polA12(ts) mutant at 43 degrees C, and its copy number
      was reduced in the E. coli pcnB80 mutant. These results prove that pEC156 is a
      ColE1-type replicon.

PMID- 11591139
TI  - Thermosensitive suicide vectors for gene replacement in Streptococcus suis.
AB  - Three thermosensitive (Ts) suicide vectors, pSET4s, pSET5s, and pSET6s, have been
      constructed for gene replacement in Streptococcus suis. Each vector contains an
      antibiotic-resistance gene (spc or cat), a Ts replication origin of pWV01
      lineage, multiple cloning sites, lacZ', and the ColE1 replication origin of
      pUC19. These vectors could be propagated at 37 degrees C in Escherichia coli, but
      their replication was blocked above 37 degrees C in S. suis. Moreover, the
      thermosensitivity of the replication origin was confirmed in S. equi ssp. equi,
      S. equi ssp. zooepidemicus, and S. dysgalactiae by using pSET4s. For inactivation
      of the sly gene, which encodes a thiol-activated hemolysin of S. suis, pSLYK, in
      which the sly gene was interrupted by the cat gene, was constructed using pSET4s
      and introduced into S. suis DAT2. After growth at the nonpermissive temperature
      under the antibiotic pressure, the chromosomal sly gene was replaced with the
      sly::cat gene of pSLYK by a double-crossover event at a rate of 2.6% among
      chloramphenicol-resistant cells. Moreover, complementation of the sly gene by use
      of the previously reported S. suis-E. coli shuttle vector pSET2 was demonstrated.
      These results indicate that the Ts suicide vectors described here will facilitate
      the genetic analysis of S. suis and other streptococci of veterinary importance
      by means of allelic exchange of the genes of interest via homologous
      recombination.

PMID- 11591140
TI  - Nucleotide sequence analysis of pRS2 and pRS3, two small cryptic plasmids from
      Oenococcus oeni.
AB  - Nucleotide sequence analysis of two cryptic plasmids, pRS2 (2544 bp) and pRS3
      (3948 bp), from Oenococcus oeni revealed the presence in both of three major open
      reading frames with significant similarity to other small cryptic plasmids from
      O. oeni. The results suggest that those plasmids could be separated into two
      subfamilies, one represented by pLo13 and pRS3, the other represented by pOg32,
      pRS1, and pRS2.

PMID- 11591141
TI  - HIV-1 gp41 six-helix bundle formation occurs rapidly after the engagement of
      gp120 by CXCR4 in the HIV-1 Env-mediated fusion process.
AB  - The onset of cell fusion mediated by HIV-1 IIIB Env is preceded by a lag phase of
      15-20 min. Fusion mediated by the CD4-independent HIV-1 Env 8x, which is capable
      of interacting directly with CXCR4, proceeds with a greatly reduced lag phase. We
      probed the intermediate steps during the lag phase in HIV-1 IIIB Env-mediated
      fusion with Leu3-a, an inhibitor of attachment of gp120 to CD4, AMD3100, an
      inhibitor of attachment of gp120 to CXCR4, and C34, a synthetic peptide that
      interferes with the transition of gp41 to the fusion active state. Inhibitions of
      fusion as a function of time of addition of C34 and of AMD3100 were equivalent,
      indicating that engagement of gp120 by CXCR4 and formation of the gp41 six-helix
      bundle follow similar kinetics. The initial steps in fusion mediated by the CD4
      independent Env 8x are too rapid for these inhibitors to interfere with. However,
      when 8x Env-expressing cells were incubated with target cells at 25 degrees C in
      the presence of AMD3100 or C34, prior to incubation at 37 degrees C, these
      inhibitors were capable of inhibiting 8x Env-mediated fusion. To further examine
      engagement of gp120 by CXCR4 and exposure of binding sites for C34, we have
      reversibly arrested the fusion reaction at 37 degrees C by adding cytochalasin B
      to the medium. We show that CXCR4 engagement and six-helix bundle formation only
      occur after the release of the cytochalasin arrest, indicating that a high degree
      of cooperativity is required to trigger the initial steps in HIV-1 Env-mediated
      fusion.

PMID- 11591142
TI  - Mapping the antagonist binding site of the serotonin type 3 receptor by
      fluorescence resonance energy transfer.
AB  - We have measured fluorescence resonance energy transfer (FRET) between a
      fluorescent antagonist, bound to the purified detergent-solubilized serotonin
      type 3 receptor, and a lipophilic acceptor probe partitioned into the micelle
      surrounding the detergent-solubilized receptor. The experimentally observed FRET
      efficiency was evaluated on the basis of the characteristic dimensions of the
      receptor-micelle complex and the average number of acceptor molecules in such
      micelles. The binding site was determined to be 5.4 +/- 0.9 nm above the center
      of the detergent micelle. The experiments were performed below the critical
      micellar concentration of the detergent (C(12)E(9)) used to solubilize the
      receptor, under which conditions it was demonstrated that the ligand binding
      activity was fully preserved. This reduces considerably the fluorescence
      background arising from probes not associated with the receptor, allowing a
      precise determination of the transfer efficiency.

PMID- 11591143
TI  - Apolipoprotein A-II/A-I ratio is a key determinant in vivo of HDL concentration
      and formation of pre-beta HDL containing apolipoprotein A-II.
AB  - Overexpression of human apolipoprotein A-II (apo A-II) in mice induced
      postprandial hypertriglyceridemia and marked reduction in plasma HDL
      concentration and particle size [Boisfer et al. (1999) J. Biol. Chem. 274, 11564
      11572]. We presently compared lipoprotein metabolism in three transgenic lines
      displaying plasma concentrations of human apo A-II ranging from normal to 4 times
      higher, under ad libitum feeding and after an overnight fast. Fasting
      dramatically decreased VLDL and lowered circulating human apo A-II in transgenic
      mice; conversely, plasma HDL levels increased in all genotypes. The apo A-I
      content of HDL was inversely related to the expression of human apo A-II,
      probably reflecting displacement of apo A-I by an excess of apo A-II. Thus, the
      molar ratios of apo A-II/A-I in HDL were significantly higher in fed as compared
      with fasted animals of the same transgenic line, while endogenous LCAT activity
      concomitantly decreased. The number and size of HDL particles decreased in direct
      proportion to the level of human apo A-II expression. Apo A-II was abundantly
      present in all HDL particles, in contrast to apo A-I mainly present in large
      ones. Two novel findings were the presence of pre-beta migrating HDL transporting
      only human apo A-II in the higher-expressing mice and the increase of plasma HDL
      concentrations by fasting in control and transgenic mice. These findings
      highlight the reciprocal modifications of VLDL and HDL induced by the feeding
      fasting transition and the key role of the molar ratio of apo A-II/A-I as a
      determinant of HDL particle metabolism and pre-beta HDL formation.

PMID- 11591144
TI  - Protein farnesyltransferase isoprenoid substrate discrimination is dependent on
      isoprene double bonds and branched methyl groups.
AB  - Farnesylation is a posttranslational lipid modification in which a 15-carbon
      farnesyl isoprenoid is linked via a thioether bond to specific cysteine residues
      of proteins in a reaction catalyzed by protein farnesyltransferase (FTase). We
      synthesized the benzyloxyisoprenyl pyrophosphate (BnPP) series of transferable
      farnesyl pyrophosphate (FPP) analogues (1a-e) to test the length dependence of
      the isoprenoid substrate on the FTase-catalyzed transfer of lipid to protein
      substrate. Kinetic analyses show that pyrophosphates 1a-e and geranyl
      pyrophosphate (GPP) transfer with a lower efficiency than FPP whereas
      geranylgeranyl pyrophosphate (GGPP) does not transfer at all. While a correlation
      was found between K(m) and analogue hydrophobicity and length, there was no
      correlation between k(cat) and these properties. Potential binding geometries of
      FPP, GPP, GGPP, and analogues 1a-e were examined by modeling the molecules into
      the active site of the FTase crystal structure. We found that analogue 1d
      displaces approximately the same volume of the active site as does FPP, whereas
      GPP and analogues 1a-c occupy lesser volumes and 1e occupies a slightly larger
      volume. Modeling also indicated that GGPP adopts a different conformation than
      the farnesyl chain of FPP, partially occluding the space occupied by the
      Ca(1)a(2)X peptide in the ternary X-ray crystal structure. Within the confines of
      the FTase pocket, the double bonds and branched methyl groups of the
      geranylgeranyl chain significantly restrict the number of possible conformations
      relative to the more flexible lipid chain of analogues 1a-e. The modeling results
      also provide a molecular explanation for the observation that an aromatic ring is
      a good isostere for the terminal isoprene of FPP.

PMID- 11591145
TI  - Interaction of 3,4-dienoyl-CoA thioesters with medium chain acyl-CoA
      dehydrogenase: stereochemistry of inactivation of a flavoenzyme.
AB  - The medium chain acyl-CoA dehydrogenase is rapidly inhibited by racemic 3,4
      dienoyl-CoA derivatives with a stoichiometry of two molecules of racemate per
      enzyme flavin. Synthesis of R- and S-3,4-decadienoyl-CoA shows that the R
      enantiomer is a potent, stoichiometric, inhibitor of the enzyme. alpha-Proton
      abstraction yields an enolate to oxidized flavin charge-transfer intermediate
      prior to adduct formation. The crystal structure of the reduced, inactive enzyme
      shows a single covalent bond linking the C-4 carbon of the 2,4-dienoyl-CoA moiety
      and the N5 locus of reduced flavin. The kinetics of reversal of adduct formation
      by release of the conjugated 2,4-diene were evaluated as a function of both acyl
      chain length and truncation of the CoA moiety. The adduct is most stable with
      medium chain length allenic inhibitors. However, the adducts with R-3,4
      decadienoyl-pantetheine and -N-acetylcysteamine are some 9- and >100-fold more
      kinetically stable than the full-length CoA thioester. Crystal structures of
      these reduced enzyme species, determined to 2.4 A, suggest that the placement of
      H-bonds to the inhibitor carbonyl oxygen and the positioning of the catalytic
      base are important determinants of adduct stability. The S-3,4-decadienoyl-CoA is
      not a significant inhibitor of the medium chain dehydrogenase and does not form a
      detectable flavin adduct. However, the S-isomer is rapidly isomerized to the
      trans-trans-2,4-conjugated diene. Protein modeling studies suggest that the S
      enantiomer cannot approach close enough to the isoalloxazine ring to form a
      flavin adduct, but can be facilely reprotonated by the catalytic base. These
      studies show that truncation of CoA thioesters may allow the design of
      unexpectedly potent lipophilic inhibitors of fatty acid oxidation.

PMID- 11591146
TI  - Glutamate 47 in 1-aminocyclopropane-1-carboxylate synthase is a major specificity
      determinant.
AB  - Glutamate 47 is conserved in 1-aminocyclopropane-1-carboxylate (ACC) synthases
      and is positioned near the sulfonium pole of (S,S)-S-adenosyl-L-methionine (SAM)
      in the modeled pyridoxal phosphate quinonoid complex with SAM. E47Q and E47D
      constructs of ACC synthase were made to investigate a putative ionic interaction
      between Glu47 and SAM. The k(cat)/K(m) values for the conversion of (S,S)-SAM to
      ACC and methylthioadenosine (MTA) are depressed 630- and 25-fold for the E47Q and
      E47D enzymes, respectively. The decreases in the specificity constants are due to
      reductions in k(cat) for both mutant enzymes, and a 5-fold increase in K(m) for
      the E47Q enzyme. Importantly, much smaller effects were observed for the kinetic
      parameters of reactions with the alternate substrates L-vinylglycine (L-VG)
      (deamination to form alpha-ketobutyrate and ammonia) and L-alanine
      (transamination to form pyruvate), which have uncharged side chains. L-VG is both
      a substrate and a mechanism-based inactivator of the enzyme [Feng, L., and
      Kirsch, J. F. (2000) Biochemistry 39, 2436-2444], but the partition ratio,
      k(cat)/k(inact), is unaffected by the Glu47 mutations. ACC synthase primarily
      catalyzes the beta,gamma-elimination of MTA from the (R,S) diastereomer of SAM to
      produce L-VG [Satoh, S., and Yang, S. F. (1989) Arch.Biochem. Biophys. 271, 107
      112], but catalyzes the formation of ACC to a lesser extent via alpha,gamma
      elimination of MTA. The partition ratios for (alpha,gamma/beta,gamma)-elimination
      on (R,S)-SAM are 0.4, < or =0.014, and < or =0.08 for the wild-type, E47Q, and
      E47D enzymes, respectively. The results of these experiments strongly support a
      role for Glu47 as an anchor for the sulfonium pole of (S,S)-SAM, and consequently
      a role as an active site determinant of reaction specificity.

PMID- 11591147
TI  - Re-engineering monovalent cation binding sites of methylamine dehydrogenase:
      effects on spectral properties and gated electron transfer.
AB  - Methylamine dehydrogenase (MADH) is a tryptophan tryptophylquinone (TTQ)
      dependent enzyme that catalyzes the oxidative deamination of primary amines.
      Monovalent cations are known to affect the spectral properties of MADH and to
      influence the rate of the gated electron transfer (ET) reaction from substrate
      reduced MADH to amicyanin. Two putative monovalent cation binding sites in MADH
      have been identified by X-ray crystallography [Labesse, G., Ferrari, D., Chen, Z.
      W., Rossi, G.-L., Kuusk, V., McIntire, W. S., and Mathews, F. S. (1998) J. Biol.
      Chem. 273, 25703-25712]. One requires cation-pi interactions involving residue
      alpha Phe55. An alpha F55A mutation differentially affects these two monovalent
      cation-dependent phenomena. The apparent K(d) associated with spectral
      perturbations increases 10-fold. The apparent K(d) associated with enhancement of
      the gated ET reaction becomes too small to measure, indicating that either it has
      decreased more than 1000-fold or the mutation has caused a conformational change
      that eliminates the requirement for the cation for the gated ET. These results
      show that of the two binding sites revealed in the structure, cation binding to
      the distal site, which is stabilized by the cation-pi interactions, is
      responsible for the spectral perturbations. Cation binding to the proximal site,
      which is stabilized by several oxygen ligands, is responsible for the enhancement
      of the rate of gated ET. Another site-directed mutant, alpha F55E MADH, exhibited
      cation binding properties that were the same as those of the native enzyme,
      indicating that interactions with the carboxylate of Glu can effectively replace
      the cation-pi interactions with Phe in stabilizing monovalent cation binding to
      the distal site.

PMID- 11591148
TI  - Kinetic and crystallographic analysis of the key active site acid/base arginine
      in a soluble fumarate reductase.
AB  - There is now overwhelming evidence supporting a common mechanism for fumarate
      reduction in the respiratory fumarate reductases. The X-ray structures of
      substrate-bound forms of these enzymes indicate that the substrate is well
      positioned to accept a hydride from FAD and a proton from an arginine side chain.
      Recent work on the enzyme from Shewanella frigidimarina [Doherty, M. K., Pealing,
      S. L., Miles, C. S., Moysey, R., Taylor, P., Walkinshaw, M. D., Reid, G. A., and
      Chapman, S. K. (2000) Biochemistry 39, 10695-10701] has strengthened the
      assignment of an arginine (Arg402) as the proton donor in fumarate reduction.
      Here we describe the crystallographic and kinetic analyses of the R402A, R402K,
      and R402Y mutant forms of the Shewanella enzyme. The crystal structure of the
      R402A mutant (2.0 A resolution) shows it to be virtually identical to the wild
      type enzyme, apart from the fact that a water molecule occupies the position
      previously taken by part of the guanidine group of R402. Although structurally
      similar to the wild-type enzyme, the R402A mutant is inactive under all the
      conditions that were studied. This implies that a water molecule, in this
      position in the active site, cannot function as the proton donor for fumarate
      reduction. In contrast to the R402A mutation, both the R402K and R402Y mutant
      enzymes are active. Although this activity was at a very low level (at pH 7.2
      some 10(4)-fold lower than that for the wild type), it does imply that both
      lysine and tyrosine can fulfill the role of an active site proton donor, albeit
      very poorly. The crystal structures of the R402K and R402Y mutant enzymes (2.0 A
      resolution) show that distances from the lysine and tyrosine side chains to the
      nearest carbon atom of fumarate are approximately 3.5 A, clearly permitting
      proton transfer. The combined results from mutagenesis, crystallographic, and
      kinetic studies provide formidable evidence that R402 acts as both a Lewis acid
      (stabilizing the build-up of negative charge upon hydride transfer from FAD to
      fumarate) and a Bronsted acid (donating the proton to the substrate to complete
      the formation of succinate).

PMID- 11591149
TI  - Hierarchical protein folding: asymmetric unfolding of an insulin analogue lacking
      the A7-B7 interchain disulfide bridge.
AB  - The landscape paradigm of protein folding can enable preferred pathways on a
      funnel-like energy surface. Hierarchical preferences may be manifest as a
      nonrandom pathway of disulfide pairing. Stepwise stabilization of structural
      subdomains among on-pathway intermediates is proposed to underlie the disulfide
      pathway of proinsulin and related molecules. Here, effects of pairwise serine
      substitution of insulin's exposed interchain disulfide bridge (Cys(A7)-Cys(B7))
      are characterized as a model of a late intermediate. Untethering cystine A7-B7 in
      an engineered monomer causes significantly more marked decreases in the
      thermodynamic stability and extent of folding than occur on pairwise substitution
      of internal cystine A6-A11 [Weiss, M. A., Hua, Q. X., Jia, W., Chu, Y. C., Wang,
      R. Y., and Katsoyannis, P. G. (2000) Biochemistry 39, 15429-15440]. Although
      substantially disordered and without significant biological activity, the
      untethered analogue contains a molten subdomain comprising cystine A20-B19 and a
      native-like cluster of hydrophobic side chains. Remarkably, A and B chains make
      unequal contributions to this folded moiety; the B chain retains native-like
      supersecondary structure, whereas the A chain is largely disordered. These
      observations suggest that the B subdomain provides a template to guide folding of
      the A chain. Stepwise organization of insulin-like molecules supports a
      hierarchic view of protein folding.

PMID- 11591150
TI  - Solution structure and dynamics of the functional domain of Paracoccus
      denitrificans cytochrome c(552) in both redox states.
AB  - A soluble and fully functional 10.5 kDa fragment of the 18.2 kDa membrane-bound
      cytochrome c(552) from Paracoccus denitrificans has been heterologously expressed
      and (13)C/(15)N-labeled to study the structural features of this protein in both
      redox states. Well-resolved solution structures of both the reduced and oxidized
      states have been determined using high-resolution heteronuclear NMR. The overall
      protein topology consists of two long terminal helices and three shorter helices
      surrounding the heme moiety. No significant redox-induced structural differences
      have been observed. (15)N relaxation rates and heteronuclear NOE values were
      determined at 500 and 600 MHz. Several residues located around the heme moiety
      display increased backbone mobility in both oxidation states, while helices I,
      III, and V as well as the two concatenated beta-turns between Leu30 and Arg36
      apparently form a less flexible domain within the protein structure. Major redox
      state-dependent differences of the internal backbone mobility on the picosecond
      nanosecond time scale were not evident. Hydrogen exchange experiments
      demonstrated that the slow-exchanging amide proton resonances mainly belong to
      the helices and beta-turns, corresponding to the regions with high order
      parameters in the dynamics data. Despite this correlation, the backbone amide
      protons of the oxidized cytochrome c(552) exchange considerably faster with the
      solvent compared to the reduced protein. Using both differential scanning
      calorimetry as well as temperature-dependent NMR spectroscopy, a significant
      difference in the thermostabilities of the two redox states has been observed,
      with transition temperatures of 349.9 K (76.8 degrees C) for reduced and 307.5 K
      (34.4 degrees C) for oxidized cytochrome c(552). These results suggest a clearly
      distinct backbone stability between the two oxidation states.

PMID- 11591151
TI  - Fluorescence resonance energy transfer shows a close helix-helix distance in the
      transmembrane M13 procoat protein.
AB  - During the membrane insertion process the major coat protein of bacteriophage M13
      assumes a conformation in which two transmembrane helices corresponding to the
      leader sequence and the anchor region in the mature part of the protein coming
      into close contact with each other. Previous studies on the molecular mechanism
      of membrane insertion of M13 procoat protein have shown that this interaction
      between the two helices might drive the actual translocation process. We
      investigated the intramolecular distance between the two helices of the
      transmembrane procoat protein by measuring fluorescence resonance energy transfer
      (FRET) between the donor (Tyr) placed in one helix and the acceptor (Trp) placed
      in the other helix. Various mutant procoat proteins with differently positioned
      donor-acceptor pairs were generated, purified, and reconstituted into artificial
      lipid bilayers. The results obtained from the FRET measurements, combined with
      molecular modeling, show that the transmembrane helices are in close contact on
      the order of 1-1.5 nm. The present approach might be of general interest for
      determining the topology and the folding of membrane proteins.

PMID- 11591152
TI  - Amino acid substitution at position 99 affects the rate of CRP subunit exchange.
AB  - We investigated the characteristics of CRP having amino acid substitutions at
      position 99. Analysis of amino acid residue proximity to cAMP in molecular
      dynamics (MD) simulations of the CRP:(cAMP)(2) complex [Garcia, A. E., and
      Harman, J. G. (1996) Protein Sci. 5, 62-71] showed repositioning of tyrosine 99
      (Y99) to interact with the equatorial exocyclic oxygen atom of cAMP. To test the
      role of Y99 in cAMP-mediated CRP activation, Y99 was substituted with alanine (A)
      or phenylalanine (F). Cells that contained the WT or mutant forms of CRP induced
      beta-galactosidase in the presence of cAMP. Purified WT, Y99A, and Y99F CRP
      showed only a 3- to 4-fold difference in cAMP affinity. There were no apparent
      differences between the three forms of CRP in cAMP binding cooperativity, in
      CRP:(cAMP)(1) complex binding to lacP DNA, in the formation of CRP:cAMP:RNAP
      complexes at lacP, or in CRP efficacy in mediating lacP activity in vitro. The
      apo-form of Y99A CRP was more sensitive to protease than the apo-form of either
      WT CRP or Y99F CRP. Whereas the WT or Y99F CRP:(cAMP)(1) complexes were cleaved
      by protease at hinge-region peptide bonds, the Y99A CRP:(cAMP)(1) complex was
      cleaved at peptide bonds located at the subunit interface. The rates of subunit
      exchange for Y99A CRP, both in the apo-form and in a 1:1 complex with cAMP, were
      significantly greater than that measured for WT CRP. The results of this study
      show that tyrosine 99 contributes significant structural stability to the CRP
      dimer, specifically in stabilizing subunit association.

PMID- 11591153
TI  - The first transmembrane segment of the dopamine D2 receptor: accessibility in the
      binding-site crevice and position in the transmembrane bundle.
AB  - The binding site of the dopamine D2 receptor, like that of homologous G-protein
      coupled receptors (GPCRs), is contained within a water-accessible crevice formed
      among its seven transmembrane segments (TMs). Using the substituted-cysteine
      accessibility method (SCAM), we are mapping the residues that contribute to the
      surface of this binding-site crevice. We have now mutated to cysteine, one at a
      time, 21 consecutive residues in TM1. Six of these mutants reacted with charged
      sulfhydryl reagents, whereas bound antagonist only protected N52(1.50)C from
      reaction. Except for A38(1.36)C, none of the substituted cysteine mutants in the
      extracellular half of TM1 appeared to be accessible. Pro(1.48) is highly
      conserved in opsins, but absent in catecholamine receptors, and the high
      resolution rhodopsin structure showed that Pro(1.48) bends the extracellular
      portion of TM1 inward toward TM2 and TM7. Analysis of the conversation of
      residues in the extracellular portion of TM1 of opsins showed a pattern
      consistent with alpha-helical structure with a conserved face. In contrast, this
      region in catecholamine receptors is poorly conserved, suggesting a lack of
      critical contacts. Thus, in catecholamine receptors in the absence of Pro(1.48),
      TM1 may be straighter and therefore further from the helix bundle, consistent
      with the apparent lack of conserved contact residues. When examined in the
      context of a model of the D2 receptor, the accessible residues in the cytoplasmic
      half of TM1 are at the interface with TM7 and with helix 8 (H8). We propose the
      existence of critical contacts of TM1, TM7, and H8 that may stabilize the
      inactive state of the receptor.

PMID- 11591154
TI  - Interaction of the human adenovirus proteinase with its 11-amino acid cofactor
      pVIc.
AB  - The interaction of the human adenovirus proteinase (AVP) and AVP-DNA complexes
      with the 11-amino acid cofactor pVIc was characterized. The equilibrium
      dissociation constant for the binding of pVIc to AVP was 4.4 microM. The binding
      of AVP to 12-mer single-stranded DNA decreased the K(d) for the binding of pVIc
      to AVP to 0.09 microM. The pVIc-AVP complex hydrolyzed the substrate with a
      Michaelis constant (K(m)) of 3.7 microM and a catalytic rate constant (k(cat)) of
      1.1 s(-1). In the presence of DNA, the K(m) increased less than 2-fold, and the
      k(cat) increased 3-fold. Alanine-scanning mutagenesis was performed to determine
      the contribution of individual pVIc side chains in the binding and stimulation of
      AVP. Two amino acid residues, Gly1' and Phe11', were the major determinants in
      the binding of pVIc to AVP, while Val2' and Phe11' were the major determinants in
      stimulating enzyme activity. Binding of AVP to DNA greatly suppressed the effects
      of the alanine substitutions on the binding of mutant pVIcs to AVP. Binding of
      either or both of the cofactors, pVIc or the viral DNA, to AVP did not
      dramatically alter its secondary structure as determined by vacuum ultraviolet
      circular dichroism. pVIc, when added to Hep-2 cells infected with adenovirus
      serotype 5, inhibited the synthesis of infectious virus, presumably by
      prematurely activating the proteinase so that it cleaved virion precursor
      proteins before virion assembly, thereby aborting the infection.

PMID- 11591155
TI  - Mutational effects at the subunit interfaces of human hemoglobin: evidence for a
      unique sensitivity of the T quaternary state to changes in the hinge region of
      the alpha 1 beta 2 interface.
AB  - A set of variant human hemoglobins, each with an Ala or Gly substitution at a
      single residue, has been prepared, and the kinetics of their reactions with
      carbon monoxide have been measured. This reaction is rate-limited by the binding
      of the first CO to the deoxygenated T state of the protein. The magnitudes of the
      effects of the mutations on CO combination vary widely, and, with the exception
      of beta Y145, the residues with the most significant effects on these kinetics
      are found in the hinge region of the alpha 1 beta 2 interface. Mixed-metal
      hybrids, with zinc protoporphyrin IX in place of heme on both alpha or both beta
      subunits, were prepared for beta W37E, beta W37A, alpha Y140G, and alpha Y140A,
      hinge region variants causing large kinetic changes, and for beta Y145G. Such
      hybrids permit measurements of the kinetics of CO binding to only the heme
      containing alpha or beta subunits within the unliganded hemoglobin tetramer.
      Mutations at beta 37 and alpha 140 have global effects on the T state, increasing
      the rates of CO binding to both types of subunits. Mutation of beta Y145 has a
      large effect on the beta subunits in the deoxygenated T state, but very little
      effect on the alpha subunits. Oxygen equilibria measurements on the crystalline T
      state of beta W37E also indicate large affinity increases in both subunits of
      this variant. The overall oxygen equilibria of the variant hemoglobins in
      solution are sensitive to numerous variables besides the properties of the
      deoxygenated T state. In contrast to CO combination kinetics, the residues whose
      alterations cause the largest changes in overall oxygen equilibria in solution
      are scattered seemingly randomly within the alpha 1 beta 2 interface.

PMID- 11591156
TI  - Studies of the mechanism of phenol hydroxylase: mutants Tyr289Phe, Asp54Asn, and
      Arg281Met.
AB  - Three residues in the active site of the flavoprotein phenol hydroxylase (PHHY)
      were independently changed by site-directed mutagenesis. One of the mutant forms
      of PHHY, Tyr289Phe, is reduced by NADPH much slower than is the wild-type enzyme,
      although it has a slightly higher redox potential than the wild-type enzyme. In
      the structure of the wild-type enzyme, residue Tyr289 is hydrogen-bonded with the
      FAD when the latter is at the "out" position but has no direct contact with the
      flavin when it is "in". The oxidative half-reaction of PHHY is not significantly
      affected by this mutation, contrary to the concept that Tyr289 is a critical
      residue in the hydroxylation reaction [Enroth, C., Neujahr, H., Schneider, G.,
      and Lindqvist, Y. (1998) Structure 6, 605-617; Ridder, L., Mullholland, A. J.,
      Rietjens, I. M. C. M., and Vervoort, J. (2000) J. Am. Chem. Soc. 122, 8728-8738].
      Tyr289 may help stabilize the FAD in the out conformation where it can be reduced
      by NADPH. For the Asp54Asn mutant form of PHHY, the initial step of the oxidative
      half-reaction is significantly slower than for the wild-type enzyme. Asp54Asn
      utilizes less than 20% of the reduced flavin for hydroxylating the substrate with
      the remainder forming H(2)O(2). Similar changes are observed when Arg281, a
      residue between Asp54 and the solvent, is mutated to Met. These two residues are
      suggested to be part of the active site environment the enzyme provides for the
      flavin cofactor to function optimally in the oxidative half-reaction. In the
      construction of the mutant forms of PHHY, it was determined that 11 of the
      previously reported amino acid residues in the sequence of PHHY were incorrect.

PMID- 11591157
TI  - Self-association of model transmembrane alpha-helices is modulated by lipid
      structure.
AB  - We have developed a fluorescence quenching method using peptides containing 3,5
      dibromotryrosine to measure oligomerization of model transmembrane alpha-helices
      in lipid bilayers. Peptides of the type Ac-LysLysGlyLeu(m)XLeu(n)LysLysAla-amide
      where X is tryptophan or 3,5-dibromotyrosine were found to form heterodimers in
      bilayers of phosphatidylcholine in the liquid-crystalline phase. The free energy
      of dimer formation changed little with increasing number of Leu residues from 16
      to 22 but increased with increasing phospholipid fatty acyl chain length, with a
      slope of about 0.5 kJ mol(-1) per fatty acyl chain carbon. Peptides were excluded
      from lipid in the gel phase, resulting in increased levels of oligomerization.
      Addition of cholesterol to form the liquid-ordered state led to increased
      dimerization but without phase separation. The presence of
      phosphatidylethanolamine had little effect on dimerization.

PMID- 11591158
TI  - Human cationic amino acid transporter hCAT-3 is preferentially expressed in
      peripheral tissues.
AB  - At least five distinct carrier proteins form the family of mammalian cationic
      amino acid transporters (CATs). We have cloned a cDNA containing the complete
      coding region of human CAT-3. hCAT-3 is glycosylated and localized to the plasma
      membrane. Transport studies in Xenopus laevis oocytes revealed that hCAT-3 is
      selective for cationic L-amino acids and exhibits a maximal transport activity
      similar to other CAT proteins. The apparent substrate affinity and sensitivity to
      trans-stimulation of hCAT-3 resembles most closely hCAT-2B. This is in contrast
      to rat and murine CAT-3 proteins that have been reported to display a very low
      activity and to be inhibited by neutral and anionic L-amino acids as well as D
      arginine (Hosokawa, H., et al. (1997) J. Biol. Chem. 272, 8717-8722; Ito, K., and
      Groudine, M. (1997) J. Biol. Chem. 272, 26780-26786). Also, in adult rat and
      mouse, CAT-3 has been found exclusively in central neurons. Human CAT-3
      expression is not restricted to the brain, in fact, by far the highest expression
      was found in thymus. Also in other peripheral tissues, hCAT-3 expression was
      equal to or higher than in most brain regions, suggesting that hCAT-3 is not a
      neuron-specific transporter.

PMID- 11591159
TI  - Heterodimer formation between the antimicrobial peptides magainin 2 and PGLa in
      lipid bilayers: a cross-linking study.
AB  - The antimicrobial peptides magainin 2 and PGLa, isolated from the skin of the
      African clawed frog Xenopus laevis, show marked synergism [Westerhoff, H. V.,
      Zasloff, M., Rosner, J. L., Hendler, R. W., de Waal, A., Vaz Gomes, A., Jongsma,
      A. P. M., Riethorst, A., and Juretic, D. (1995) Eur. J. Biochem. 228, 257-264].
      We suggested previously that these peptides form a potent heterodimer composed of
      either parallel or antiparallel helices in membranes [Matsuzaki, K., Mitani, Y.,
      Akada, K., Murase, O., Yoneyama, S., Zasloff, M., and Miyajima, K. (1998)
      Biochemistry 37, 15144-15153]. To detect the putative heterodimer by chemical
      cross-linking, analogues of magainin 2 and PGLa with a Cys residue at either
      terminus were synthesized. These cross-linking experiments suggested that both
      peptides form a parallel heterodimer in membranes composed of
      phosphatidylglycerol/phosphatidylcholine but not in either buffer or a helix
      promoting 2,2,2-trifluoroethanol/buffer mixture. The isolated parallel
      heterodimers exhibited an order of magnitude higher membrane permeabilization
      activity compared with the monomeric species, indicating that the observed
      synergism is due to heterodimer formation.

PMID- 11591160
TI  - Identification of the catalytic residue of Thermococcus litoralis 4-alpha
      glucanotransferase through mechanism-based labeling.
AB  - Thermococcus litoralis 4-alpha-glucanotransferase (TLGT) belongs to family 57 of
      glycoside hydrolases and catalyzes the disproportionation and cycloamylose
      synthesis reactions. Family 57 glycoside hydrolases have not been well
      investigated, and even the catalytic mechanism involving the active site residues
      has not been studied. Using 3-ketobutylidene-beta-2-chloro-4-nitrophenyl
      maltopentaoside (3KBG5CNP) as a donor and glucose as an acceptor, we showed that
      the disproportionation reaction of TLGT involves a ping-pong bi-bi mechanism. On
      the basis of this reaction mechanism, the glycosyl-enzyme intermediate, in which
      a donor substrate was covalently bound to the catalytic nucleophile, was trapped
      by treating the enzyme with 3KBG5CNP in the absence of an acceptor and was
      detected by matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry after peptic digestion. Postsource decay analysis suggested that
      either Glu-123 or Glu-129 was the catalytic nucleophile of TLGT. Glu-123 was
      completely conserved between family 57 enzymes, and the catalytic activity of the
      E123Q mutant enzyme was greatly decreased. On the other hand, Glu-129 was a
      variable residue, and the catalytic activity of the E129Q mutant enzyme was not
      decreased. These results indicate that Glu-123 is the catalytic nucleophile of
      TLGT. Sequence alignment of TLGT and family 38 enzymes (class II alpha
      mannosidases) revealed that Glu-123 of TLGT corresponds to the nucleophilic
      aspartic acid residue of family 38 glycoside hydrolases, suggesting that family
      57 and 38 glycoside hydrolases may have had a common ancestor.

PMID- 11591161
TI  - Malonyl-CoA:ACP transacylase from Streptomyces coelicolor has two alternative
      catalytically active nucleophiles.
AB  - Fatty acids and polyketides are synthesized by mechanistically and evolutionarily
      related multienzyme systems. Their carbon chain backbones are synthesized via
      repeated decarboxylative condensations of alpha-carboxylated building blocks onto
      a growing acyl chain. These alpha-carboxylated building blocks are transferred
      from the corresponding coenzyme A thioesters onto the phosphopantetheine arm of
      an acyl carrier protein (ACP) by acyl transferases, which operate by a ping-pong
      mechanism involving an acyl-O-serine intermediate. In the course of our studies
      on the malonyl-CoA:ACP transacylase (MAT) from Streptomyces coelicolor, we
      observed that an active-site Ser (97) --> Ala mutant retains activity as well as
      the ability to be covalently labeled by (14)C malonyl-CoA. Here we demonstrate
      that an alternative, catalytically competent nucleophile exists in the active
      site of this enzyme. Next to the active-site serine is a histidine residue that
      is conserved in some, but not all acyl transferases. The H96A mutant is also
      active and can be labeled, but an H96A/S97A double mutant is inactive and cannot
      be labeled. The ability of H96 to form a malonyl-imidazole adduct was confirmed
      by proteolysis, followed by radio-HPLC and mass spectrometric analysis of the
      S97A mutant enzyme. Kinetic analysis revealed that the k(cat) of the S97A mutant
      was within 10-fold that of the wild-type enzyme, whereas the K(M)s of the two
      enzymes were comparable. Sequence comparison with the E. coli MAT (whose X-ray
      structure is known) led to the identification of H201 as the putative base in the
      serine-histidine catalytic dyad of the S. coelicolor enzyme. The absence of MAT
      activity in the H201A mutant and the detection of weak activity in the H201Q
      mutant was consistent with this proposal. The implications of this unexpected
      finding are discussed.

PMID- 11591162
TI  - The mechanism of dienoyl-CoA reduction by 2,4-dienoyl-CoA reductase is stepwise:
      observation of a dienolate intermediate.
AB  - The chemical mechanism of the 2,4-dienoyl-CoA reductase (EC 1.3.1.34) from rat
      liver mitochondria has been investigated. This enzyme catalyzes the NADPH
      dependent reduction of 2,4-dienoyl-coenzyme A (CoA) thiolesters to the resulting
      trans-3-enoyl-CoA. Steady-state kinetic parameters for trans-2,trans-4
      hexadienoyl-CoA and 5-phenyl-trans-2,trans-4-pentadienoyl-CoA were determined and
      demonstrated that the dienoyl-CoA and NADPH bind to the 2,4-dienoyl-CoA reductase
      via a sequential kinetic mechanism. Kinetic isotope effect studies and the
      transient kinetics of substrate binding support a random order of nucleotide and
      dienoyl-CoA addition. The large normal solvent isotope effects on V/K
      ((D)(2)(O)V/K) and V ((D)(2)(O)V) for trans-2,trans-4-hexadienoyl-CoA reduction
      indicate that a proton transfer step is rate limiting for this substrate. The
      stability gained by conjugating the phenyl ring to the diene in PPD-CoA results
      in the reversal of the rate-determining step, as evidenced by the normal isotope
      effects on V/K(CoA) ((D)V/K(CoA)) and V/K(NADPH) ((D)V/K(NADPH)). The reversal of
      the rate-determining step was supported by transient kinetics where a burst was
      observed for the reduction of trans-2,trans-4-hexadienoyl-CoA but not for 5
      phenyl-trans-2,trans-4-pentadienoyl-CoA reduction. The chemical mechanism is
      stepwise where hydride transfer from NADPH occurs followed by protonation of the
      observable dienolate intermediate, which has an absorbance maximum at 286 nm. The
      exchange of the C alpha protons of trans-3-decenoyl-CoA, catalyzed by the 2,4
      dienoyl-CoA reductase, in the presence of NADP(+) suggests that formation of the
      dienolate is catalyzed by the enzyme active site.

PMID- 11591163
TI  - Fluorescence anisotropy measurements of lipid order in plasma membranes and lipid
      rafts from RBL-2H3 mast cells.
AB  - Specialized plasma membrane domains known as lipid rafts participate in signal
      transduction and other cellular processes, and their liquid ordered (L(o)) phase
      appears to be important for their function. To quantify ordered lipids in
      biological membranes, we investigated steady-state fluorescence anisotropy of two
      lipid probes, 2-[3-(diphenylhexatrienyl)propanoyl]-1-hexadecanoyl-sn-glycero-3
      phosphocholine (DPH-PC) and N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2
      dihexadecanoyl-sn-glycero-3-phosphoethanolamine (NBD-PE). We show using model
      membranes with varying amounts of cholesterol that steady-state fluorescence
      anisotropy is a sensitive measure of cholesterol-dependent ordering. The results
      suggest that DPH-PC is a more sensitive probe than NBD-PE. In the presence of
      cholesterol, ordering also depends on the degree of saturation of the
      phospholipid acyl chains. Using DPH-PC, we find that the plasma membrane of RBL
      2H3 mast cells is substantially ordered, roughly 40%, as determined by comparison
      with anisotropy values for model membranes entirely in a liquid ordered (L(o))
      phase and in a liquid disordered (L(alpha)) phase. This result is consistent with
      the finding that approximately 30% of plasma membrane phospholipids are insoluble
      in 0.5% Triton X-100. Furthermore, detergent-resistant membranes isolated by
      sucrose gradient fractionation of Triton X-100 cell lysates are more ordered than
      plasma membrane vesicles, suggesting that they represent a more ordered subset of
      the plasma membrane. Treatment of plasma membrane vesicles with methyl-beta
      cyclodextrin resulting in 75% cholesterol depletion leads to commensurate
      decreases in lipid order as measured by anisotropy of DPH-PC and NBD-PE. These
      results demonstrate that steady-state fluorescence anisotropy of DPH-PC is a
      useful way to measure the amount of lipid order in biological membranes.

PMID- 11591164
TI  - The carboxy-terminal calcium binding sites of calmodulin control calmodulin's
      switch from an activator to an inhibitor of RYR1.
AB  - Calcium and calmodulin both regulate the skeletal muscle calcium release channel,
      also known as the ryanodine receptor, RYR1. Ca(2+)-free calmodulin
      (apocalmodulin) activates and Ca(2+)-calmodulin inhibits the ryanodine receptor.
      The conversion of calmodulin from an activator to an inhibitor is due to Ca(2+)
      binding to calmodulin. We have previously shown that the binding sites for
      apocalmodulin and Ca(2+)-calmodulin on RYR1 are overlapping with the Ca(2+)
      calmodulin site located slightly N-terminal to the apocalmodulin binding site. We
      now show that mutations of the calcium binding sites in either the N-terminal or
      the C-terminal lobes of calmodulin decrease the affinity of calmodulin for the
      ryanodine receptor, suggesting that both lobes interact with RYR1. Mutation of
      the two C-terminal Ca(2+) binding sites of calmodulin destroys calmodulin's
      ability to inhibit ryanodine receptor activity at high calcium concentrations.
      The mutated calmodulin, however, can still bind to RYR1 at both nanomolar and
      micromolar Ca(2+) concentrations. Mutating the two N-terminal calcium binding
      sites of calmodulin does not significantly alter calmodulin's ability to inhibit
      ryanodine receptor activity. These data suggest that calcium binding to the two C
      terminal calcium binding sites within calmodulin is responsible for the switching
      of calmodulin from an activator to an inhibitor of the ryanodine receptor.

PMID- 11591165
TI  - Dynamic impact of methylation at the M. Hhai target site: a solid-state deuterium
      NMR study.
AB  - Base methylation plays an important role in numerous biological functions of DNA,
      from inhibition of cleavage by endonucleases to inhibition of transcription
      factor binding. Studies of nucleic acid structure have shown little differences
      in unmethylated DNAs and the identical sequence containing methylated analogues.
      We have investigated changes in the local dynamics of DNA upon substitution of a
      methylated cytosine analogue for cytosine using solid-state deuterium NMR. In
      particular, we have observed changes in the local dynamics at the target site of
      the M. HhaI restriction system. These studies observe changes in the amplitudes
      of the local backbone dynamics at the actual target site of the HhaI
      methyltransferase. This conclusion is another indication that the significant
      result of base methylation is to perturb the local dynamics, and therefore the
      local conformational flexibility, of the DNA helix, inhibiting or restricting the
      protein's ability to manipulate the DNA helix in order to perform its chemical
      alterations.

PMID- 11591166
TI  - Chromophore attachment to biliproteins: specificity of PecE/PecF, a lyase
      isomerase for the photoactive 3(1)-cys-alpha 84-phycoviolobilin chromophore of
      phycoerythrocyanin.
AB  - PecE and PecF, the products of two phycoerythrocyanin lyase genes (pecE and pecF)
      of Mastigocladus laminosus (Fischerella), catalyze two reactions: (1) the
      regiospecific addition of phycocyanobilin (PCB) to Cys-alpha 84 of the
      phycoerythrocyanin alpha-subunit (PecA), and (2) the Delta 4-->Delta 2
      isomerization of the PCB to the phycoviolobilin (PVB)-chromophore [Zhao et al.
      (2000) FEBS Lett. 469, 9-13]. The alpha-apoprotein (PecA) as well PecE and PecF
      were overexpressed from two strains of M. laminosus, with and without His-tags.
      The products of the spontaneous addition of PCB to PecA, and that of the reaction
      catalyzed by PecE/F, were characterized by their photochemistry and by
      absorption, fluorescence, circular dichroism of the four states obtained by
      irradiation with light (15-Z/E isomers of the chromophore) and/or modification of
      Cys-alpha 98/99 with thiol-directed reagents. The spontaneous addition leads to a
      3(1)-Cys-PCB adduct, which is characteristic of allophycocyanins and
      phycocyanins, while the addition catalyzed by PecE and PecF leads to a 3(1)-Cys
      PVB adduct which after purification was identical to alpha-PEC. The specificity
      and kinetics of the chromophore additions were investigated with respect to the
      structure of the bilin substrate: The 3-ethylidene-bilins, viz., PCB, its 18
      vinyl analogue phytochromobilin, phycoerythrobilin and its dimethylester, react
      spontaneously to yield the conventional addition products (3-H, 3(1)-Cys), while
      the 3-vinyl-substituted bilins, viz., bilirubin and biliverdin, were inactive.
      Only phycocyanobilin and phytochromobilin are substrates to the addition
      isomerization reaction catalyzed by PecE/F. The slow spontaneous addition of
      phycoerythrobilin is not influenced, and there is in particular no catalyzed
      isomerization to urobilin.

PMID- 11591167
TI  - alpha beta Spectrin coiled coil association at the tetramerization site.
AB  - On the basis of sequence homology studies, it has been suggested that the
      association of human erythrocytes alpha and beta spectrin at the tetramerization
      site involves interactions between helices. However, no empirical details are
      available, presumably due to the experimental difficulties in studying spectrin
      molecules because of its size and/or its structural flexibility. It has been
      speculated that erythrocyte tetramerization involves helical bundling rather than
      coiled coil association. We have used recombinant spectrin peptides to model
      alpha and beta spectrin to study their association at the tetramerization site.
      Two alpha peptides, Sp alpha 1-156 and Sp alpha 1-368, and one beta peptide, Sp
      beta 1898-2083, were used as model peptides to demonstrate the formation of the
      alpha beta complex. We also found that the replacement of R28 in Sp alpha 1-368
      to give Sp alpha 1-368R28C abolished complex formation with the beta peptide.
      Circular dichroism techniques were used to monitor the secondary structures of
      the individual peptides and of the complex, and the results showed that both Sp
      alpha 1-156 and Sp beta 1898-2083 peptides in solution, separately, included
      helices that were not paired with other helices in the absence of their binding
      partners. However, in a mixture of Sp alpha 1-156 and Sp beta 1898-2083 and
      formation of the alpha beta complex, the unpaired helices associated to form
      coiled coils. Since the sequences of these two peptides that are involved in the
      coiled coil association are derived from a native protein, the information
      obtained from this study also provides insight toward a better understanding of
      naturally occurring coiled coil subunit-subunit association.

PMID- 11591169
TI  - The role of nutritional therapy in the treatment of equine Cushing's syndrome and
      laminitis.
AB  - Equine Cushing's syndrome, a relatively common and complex condition, is
      difficult to treat with conventional medicine. Cushing's syndrome involves a
      hyperplasia or adenoma of the anterior pituitary gland. Biochemical alterations
      include increased endogenous cortisol, insulin resistance, elevated
      adrenocorticotrophic hormone, and decreased thyroid hormone levels. Symptoms
      include hirsutism with no loss of the winter coat in summer, refractory
      laminitis, weight problems (over- or underweight), polyuria/polydipsia (Pu/Pd),
      frequent infections, lowered immunity to intestinal parasites, decreased
      intestinal wall integrity, and infertility. Laminitis (an inflammation of the
      laminae of the foot) is a common and often fatal complication of Cushing's
      syndrome that tends to be refractory to conventional treatment. One of the most
      common therapies is phenylbutazone, a non-steroidal anti-inflammatory drug
      (NSAID) known to cause significant changes in the permeability of the intestinal
      wall. Recent research has shown an intestinal bacterial exotoxin to be one of the
      triggering factors in laminitis. By removing phenylbutazone and healing the
      intestinal wall, laminitis becomes more responsive to treatment. Good hoof-care
      combined with nutritional management and the application of other modalities,
      including acupuncture and Chinese and Western herbs, can complete the healing
      process. The successful treatment of equine Cushing's syndrome is one of the best
      examples of treating a disease using the holistic approach. While each case
      requires different combinations of modalities, the outcome is usually positive
      with individually selected treatments.

PMID- 11591170
TI  - Nutrients and botanicals in the treatment of diabetes in veterinary practice.
AB  - Diabetes mellitus can be frustrating to treat in veterinary practice, but
      botanical and nutritional supplements may offer assistance in stabilizing
      difficult patients. While dogs are typically subject to type 1 diabetes, cats
      develop type 2 diabetes as much as 70 percent of the time. Whereas treatment
      adjuncts to insulin may address carbohydrate metabolism from glucose absorption
      to insulin receptor function, success may depend on the type of diabetes present
      in the patient.

PMID- 11591171
TI  - Compromised hepatic detoxification in companion animals and its correction via
      nutritional supplementation and modified fasting.
AB  - Dietary components play a crucial role in the health of companion animals,
      especially those exposed to elevated levels of toxins and free radicals.
      Investigation into animals' hepatic antioxidant and metabolite conjugation
      systems, and the metabolic processes that influence them, provides some
      understanding regarding the relationship of diet to disease prevention and
      treatment. A review of current literature and research publications suggests
      nutritional supplementation can be an effective treatment for animals suffering
      from increased oxidative stress and toxicity. The results of recent in vivo
      assessments, clinical trials, and observational studies show oral supplementation
      with vitamin E, selenium, glutathione, and taurine to be beneficial for both
      maintaining natural antioxidant systems and protecting against a number of
      degenerative diseases associated with free radical damage and toxin exposure. In
      many instances, it has been observed that the introduction of specific nutrients
      positively influences the health status, symptomatic presentation, and life span
      of animals whose natural detoxification systems are compromised.

PMID- 11591172
TI  - Nutritional therapy in the treatment of heart disease in dogs.
AB  - A number of diseases affecting the heart are prevalent in canines. Acquired
      diseases, those which develop over the course of an animal's lifetime (rather
      than congenital defects present at birth), have recently been the subject of
      several studies to determine the efficacy of dietary supplementation on symptom
      presentation, disease severity, and mortality rates. Specifically, coenzyme Q10
      (CoQ10), vitamin E (as alpha-tocopherol), L-carnitine, taurine, and fish oil
      (omega-3 fatty acids) have all been evaluated in the prevention and treatment of
      many types of heart disease in dogs. Other supplements with preliminary evidence,
      meriting further investigation, include magnesium, Crataegus, and the B vitamins.
      Both clinical observation and interventional trials with various breeds have
      provided clear evidence for the benefit of numerous supplements on canine heart
      disease. Appropriate levels of certain dietary nutrients have been shown to
      increase life span, improve life quality, reduce symptoms and physical evidence
      of disease, and decrease mortality rates in these animals.

PMID- 11591173
TI  - Renal disease in small animals: a review of conditions and potential nutrient and
      botanical interventions.
AB  - Nutritional and botanical approaches that may benefit small animals diagnosed
      with renal disease are considered with regard to their effects on renal
      physiology and ability to ameliorate specific pathologies. Suggestions are made
      for water- and fat-soluble vitamins, mushrooms, quercetin, and Western and
      Chinese herbs, based on their activities as free-radical scavengers, immune
      modulators, antimicrobials, anti-emetics, and erythrocyte production stimulators.
      Attention is focused on omega-3 fatty acids from fish and flaxseed, in addition
      to several other nutrients and botanicals. Renal anatomy and physiology is
      reviewed, as well as the etiology of chronic renal disease in small animals, its
      symptomatic presentation, and progression.

PMID- 11591174
TI  - Curcuma longa (turmeric). Monograph.
AB  - Curcuma longa, a perennial herb, is a member of the Zingiberaceae (ginger)
      family. The plant grows to a height of three to five feet, and is cultivated
      extensively in Asia, India, China, and other countries with a tropical climate.
      It has oblong, pointed leaves and bears funnel-shaped yellow flowers. The rhizome
      is the portion of the plant used medicinally; it is usually boiled, cleaned, and
      dried, yielding a yellow powder. Dried Curcuma longa is the source of the spice
      turmeric, the ingredient that gives curry powder its characteristic yellow color.
      Turmeric is used extensively in foods for both its flavor and color. Turmeric has
      a long tradition of use in the Chinese and Ayurvedic systems of medicine,
      particularly as an anti-inflammatory agent, and for the treatment of flatulence,
      jaundice, menstrual difficulties, hematuria, hemorrhage, and colic. Turmeric can
      also be applied topically in poultices to relieve pain and inflammation. Current
      research has focused on turmeric's antioxidant, hepatoprotective, anti
      inflammatory, anticarcinogenic, and antimicrobial properties, in addition to its
      use in cardiovascular disease and gastrointestinal disorders.

PMID- 11591175
TI  - p21(WAF1) is associated with CDK2 and CDK4 protein during HL-60 cell
      differentiation by TPA treatment.
AB  - TPA-treated HL-60 cells are mainly arrested in G1 by p21(WAF1) accumulation. We
      investigate the downstream changes following such accumulation. Increased
      p21(WAF1) is associated with CDK2 and CDK4. pRb is dephosphorylated in the
      presence of p21-CDK2/4 complexes, and the Rb-E2F1 complex increases after TPA
      treatment, whereas the Rb-HDAC1 complex decreases slightly. Our results suggest
      that increased p21(WAF1) is associated with CDK2/4, and that these complexes
      induce pRb dephosphorylation. In turn, hypophosphorylated pRb are mainly
      complexed with E2F1, but HDAC1 appears not to be a key component in this process.

PMID- 11591176
TI  - Cell volume and rate of proliferation, but not protein expression pattern,
      distinguish pup/intimal smooth muscle cells from subcultured adult smooth muscle
      cells.
AB  - Smooth muscle cells from neonatal rats and from injured blood vessels grow with a
      characteristic cobblestone morphology that distinguishes them from adult smooth
      muscle cells. This has led to the proposition that there are two distinct types
      of smooth muscle cells with different proliferative capacity. Here we
      systematically compare the properties of subcultured adult smooth muscle cells in
      culture and clonal lines of cobblestone smooth muscle cells from both neonatal
      rats and injured vessels. The cobblestone smooth muscle cells have a
      significantly smaller average cell volume, estimated using two different flow
      cytometry measurements. However, the two types of smooth muscle cells have
      indistinguishable protein expression patterns when the levels of more than 20
      different proteins (including cytoskeletal proteins, matrix proteins, cytokines,
      cytokine receptors, adhesion molecules and enzymes) are measured by quantitative
      immunofluorescence. Furthermore, in contrast to previous observations, we
      demonstrate that both types of smooth muscle cells secrete a powerful mitogenic
      activity. The higher cell density achieved by the cobblestone smooth muscle cells
      in culture was responsible for the earlier reports that this mitogenic activity
      was secreted only by cobblestone smooth muscle cells. We conclude that many of
      the differences seen between cobblestone smooth muscle cells and adult smooth
      muscle cells in vitro (proliferation rate, morphology, protein expression
      pattern, secretion of mitogenic activity) could be attributable to a stable
      difference in the median cell volume of the cultures.

PMID- 11591177
TI  - Effects of the flavonoid baicalin and its metabolite baicalein on androgen
      receptor expression, cell cycle progression and apoptosis of prostate cancer cell
      lines.
AB  - Recent studies on the Chinese herbal medicine PC SPES showed biological
      activities against prostate cancer in vitro, in vivo and in patients with
      advanced stages of the disease. In investigating its mode of action, we have
      isolated a few of the active compounds. Among them, baicalin was the most
      abundant (about 6%) in the ethanol extract of PC SPES, as determined by HPLC.
      Baicalin is known to be converted in vivo to baicalein by the cleavage of the
      glycoside moiety. Therefore, it is useful to compare their activities in vitro.
      The effects of baicalin and baicalein were studied in androgen-positive and 
      negative human prostate cancer lines LNCaP and JCA-1, respectively. Inhibition of
      cell growth by 50% (ED(50)) in LNCaP cells was seen at concentrations of 60.8 +/-
      3.2 and 29.8 +/- 2.2 microM baicalin and baicalein, respectively. More potent
      growth inhibitory effects were observed in androgen-negative JCA-1 cells, for
      which the ED(50) values for baicalin and baicalein were 46.8 +/- 0.7 and 17.7 +/-
      3.4, respectively. Thus, it appears that cell growth inhibition by these
      flavonoids is independent of androgen receptor status. Both agents (1) caused an
      apparent accumulation of cells in G(1) at the ED(50) concentration, (2) induced
      apoptosis at higher concentrations, and (3) decreased expression of the androgen
      receptor in LNCaP cells.

PMID- 11591178
TI  - Quiescence, cell viability, apoptosis and necrosis of smooth muscle cells using
      different growth inhibitors.
AB  - Smooth muscle cells and endothelial cells play an important role in
      cardiovascular diseases and may therefore be a potential target for gene therapy.
      Most in vitro experiments are performed using proliferating cell cultures.
      Nevertheless, non-dividing cells would represent more realistic in vivo
      conditions for gene therapy. Therefore, a simple method to achieve
      physiologically quiescence in cell cultures is needed for experiments. Growth to
      confluence is sufficient for endothelial cells to reach quiescence, in contrast
      to smooth muscle cells. Alternative techniques were investigated to achieve
      quiescence for smooth muscle cells. N-acetyl-cysteine, heparin, aphidicolin and
      serum-free medium are known inhibitors of smooth muscle cell proliferation and
      were tested for cell viability, necrosis and apoptosis. The inhibition status was
      evaluated counting cells in a cell counter. Toxicity, necrosis and apoptosis were
      determined using FACS analysis. Then, smooth muscle cells and endothelial cells
      were transfected with plasmid containing the beta-galactosidase gene using
      liposomes. Analysis of gene expression in transfected cells included a
      quantitative beta-galactosidase assay and X-gal staining. Growth inhibition was
      achieved with all agents tested. Using N-acetyl-cysteine, only slightly reduced
      growth rates were observed. Aphidicolin stopped cell growth almost immediately,
      but demonstrated enhanced toxicity. The amount of apoptotic and necrotic cells
      was lowest using heparin in the presence of foetal calf serum. Transfection
      experiments using stationary cultures of smooth muscle cells using heparin or
      aphidicolin demonstrated 5-10-fold lower transfection rates compared to
      transfected proliferating cell cultures serving as controls. Transfection
      experiments using stationary cultures of endothelial cells using growth
      inhibition through confluence demonstrated 40-fold lower transfection rates than
      transfected proliferating cell cultures. Transfer efficiency was much lower in
      endothelial cells compared to smooth muscle cells. In conclusion, quiescent cells
      simulate more realistically the in vivo situation and may therefore represent a
      better model for future in vivo experiments based on in vitro findings.

PMID- 11591179
TI  - Cell cycle distribution of primitive haematopoietic cells stimulated in vitro and
      in vivo.
AB  - A novel approach is used to study the proliferating behaviour of primitive
      haematopoietic cell populations in response to different stimuli. A mathematical
      model based on the average proportion of apoptotic, dividing and quiescent cells
      in primitive haematopoietic cell populations is developed to describe the mitotic
      history of 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester-labelled
      cells. The cell cycle distributions in different cytokine-supplemented cultures
      of primitive human and mouse bone marrow cells are determined and compared with
      those found in vivo. The results indicate that a combination of flt-3 ligand,
      Steel factor and interleukin-11 or hyper-interleukin-6 provide a level of
      mitogenic stimulation similar to that existing in vivo after a myeloablative
      radiation dose. The comparison of the cell cycle distribution obtained for
      different cultures of human bone marrow CD34(+)(45RA/71)(-) cells demonstrates
      that the addition of flt-3 ligand in these cultures decreases apoptosis
      significantly but does not reduce quiescence. In addition, in vivo and in vitro,
      it was found that more than 3 days of stimulation are required to recruit a
      maximum number of quiescent cells into active cell cycle. These kinetics of cell
      cycle activation are found to be similar to those identified for the
      haematopoietic stem cells compartment in the same cultures. This mathematical
      analysis provides a useful tool for the development of haematopoietic stem cell
      culture processes for clinical applications.

PMID- 11591180
TI  - Does pregnancy prevent atopy?

PMID- 11591181
TI  - Inhaled sodium cromoglycate in the management of asthma: should it be consigned
      to history?

PMID- 11591182
TI  - H(1)-antihistamines and inflammation.

PMID- 11591183
TI  - The role of IgE in allergen-induced inflammation and the potential for
      intervention with a humanized monoclonal anti-IgE antibody.

PMID- 11591184
TI  - Maternal atopy and parity.
AB  - BACKGROUND: Family size and high birth order were related to the prevalence of
      hayfever and positive skin prick test. However, this association may be explained
      by maternal atopy. We examined the relationship between maternal atopy and the
      number of offspring in three European cohorts of pregnant women. METHODS: The
      mothers and their children (n = 1487) were recruited for the Asthma Multi-centre
      Infants Cohort Study (AMICS). The three concurrent cohorts (Ashford, Kent (UK);
      Menorca island (Spain) and Barcelona city (Spain) followed the same research
      protocol. Maternal and paternal atopy was identified by skin prick tests at
      different times at the three centres. RESULTS: Maternal atopy was inversely
      related to the number of offspring, an association which occurred in each of the
      three cohorts and remained when atopy was defined separately for individual
      allergens (a positive response to testing with either Der p 1 or grass pollen)
      and which was not confounded by maternal age, smoking nor social class (the
      adjusted odds ratios were 0.71, 0.79 and 0.26 for increasing number of offspring,
      P = 0.002). Neither maternal asthma (P = 0.43) nor paternal atopy (P = 0.58) were
      associated with the number of offspring. Maternal atopy was not related to
      reproductive outcomes. CONCLUSIONS: The association between maternal atopy and
      parity challenges the role of family size on child atopy, which should be studied
      in other populations.

PMID- 11591185
TI  - Sodium cromoglycate attenuates pulmonary inflammation without influencing
      bronchial responsiveness in healthy subjects exposed to organic dust.
AB  - BACKGROUND: Inhalation of organic dust from a pig house induces airway
      inflammation and increases bronchial responsiveness to methacholine in healthy
      subjects. OBJECTIVE: To study whether sodium cromoglycate influences the airway
      inflammatory reaction and the increase in airway responsiveness induced by
      inhalation of organic dust. METHODS: Bronchoalveolar and nasal lavages, and
      bronchial methacholine challanges were performed and blood samples were drawn in
      32 healthy subjects before and after exposure to dust in a pig farm. Sodium
      cromoglycate was inhaled (20 mg, twice a day) and administered intranasally (5.2
      mg, twice a day) by 16 and a corresponding placebo was given to the other 16
      healthy controls for two weeks prior to exposure. RESULTS: Exposure induced a
      significant increase in inflammatory cells and soluble components (pro
      inflammatory cytokines, inflammatory mediators) in bronchoalveolar and nasal
      lavage fluid in both groups. The increase in neutrophils, interleukin (IL)-6 and
      tumour necrosis factor (TNF)-alpha as well as myeloperoxidase and soluble
      intracellular adhesion molecule (ICAM)-1 in bronchoalveolar lavage (BAL) fluid
      was significantly reduced by treatment with sodium cromoglycate. Although sodium
      cromoglycate inhalation largely influenced a variety of inflammatory indices in
      bronchoalveolar lavage fluid it had no effect on the increase in bronchial
      responsiveness to methacholine. CONCLUSION: Sodium cromoglycate alters the airway
      inflammatory response to inhaled organic dust without influencing the dust
      induced increase in bronchial responsiveness to methacholine.

PMID- 11591186
TI  - Inhibition of cytokine generation and mediator release by human basophils treated
      with desloratadine.
AB  - BACKGROUND: Desloratadine is a non-sedating, clinically effective, anti-allergic
      therapy that has been shown to exhibit anti-inflammatory properties that extend
      beyond its ability to antagonize histamine at H(1)-receptor sites. This latter
      effect has been shown in vitro to be both IgE-dependent and -independent.
      OBJECTIVE: In this study, we addressed the ability of desloratadine to inhibit
      the in vitro generation of interleukin (IL)-4 and IL-13 from human basophils
      while concurrently comparing its efficacy in preventing mediator release by these
      cells. METHODS: Basophil-enriched suspensions were treated with various
      concentrations of desloratadine for 15 min before stimulating with either anti
      IgE antibody, calcium ionophore, IL-3 or phorbol ester. Histamine (fluorimetry),
      LTC(4) (RIA) and IL-4 (ELISA) were all assayed using the same 4-h culture
      supernatants. IL-13 (ELISA) was measured in supernatants harvested after 20 h
      incubation. IL-4 mRNA expression (dilutional RT-PCR) was also examined. RESULTS:
      Desloratadine was found to be nearly six-seven times more potent in preventing
      the secretion of IL-4 and IL-13 induced by anti-IgE than it was at inhibiting the
      release of histamine and LTC(4). These cytokines were equally inhibited by
      desloratadine following activation with ionomycin despite the lack of an effect
      on the histamine induced with ionomycin. Desloratadine had a lesser effect
      regarding inhibition of the IL-13 secreted in response to IL-3 and PMA. There was
      no evidence that desloratadine mediated its inhibitory effects by causing
      decreased cell viability. Finally, IL-4 mRNA accumulation was remarkably
      inhibited, by as much as 80%, following pretreatment with desloratadine.
      CONCLUSION: While capable of inhibiting histamine and LTC(4) release by human
      basophils, desloratadine is more effective at targeting the signals regulating IL
      4 and IL-13 generation in these cells. This inhibitory effect on cytokine
      generation provides additional evidence that this antihistamine exerts anti
      inflammatory properties.

PMID- 11591187
TI  - Cetirizine inhibits skin reactions but not mediator release in immediate and
      developing late-phase allergic cutaneous reactions. A double-blind, placebo
      controlled study.
AB  - BACKGROUND: Recent reports have indicated cetirizine, a potent H(1)-receptor
      antagonist, to possess a number of anti-inflammatory effects, e.g. inhibition of
      mast cell degranulation and inhibition of leucocyte migration and activation.
      OBJECTIVE: The aim of this study was to compare the effects of cetirizine on skin
      responses and mediator release in intact skin in immediate and developing late
      phase allergic reactions by microdialysis technique. METHODS: Cetirizine 10 mg
      once daily or matching placebo were administered to 10 atopic subjects for 6 days
      followed by a 2-week washout in a randomized, double-blind, placebo-controlled,
      cross-over trial. Immediate skin test responses to allergen, codeine, and
      histamine and late-phase reactions to allergen were assessed. The time course of
      extracellular levels of inflammatory mediators in intact skin were monitored by
      microdialysis techniques using 2 kDa and 3 MDa cut-off fibers, respectively.
      RESULTS: Cetirizine significantly reduced immediate weal and flare reactions to
      allergen, codeine, and histamine. Injection of allergen, but not buffer controls,
      induced a significant release of histamine, tryptase, prostaglandin D(2), total
      protein, and eosinophilic cationic protein. No significant increase of
      leukotriene B(4) and myeloperoxidase was observed. Cetirizine inhibited early
      total protein extravasation by 40%, but this did not reach a significant level.
      None of the inflammatory mediators were significantly inhibited by cetirizine.
      Cetirizine significantly reduced the late-phase skin induration to allergen by
      approximately 30%. CONCLUSION: Cetirizine potently reduced skin responses in
      immediate allergic reactions without inhibition of early mediators. These data
      indicate cetirizine to be a potent H1-receptor antagonist with no effect on mast
      cell activation. It did not inhibit any of the late-phase mediators, but it
      reduced the late skin reaction. These data suggest that mediators other than
      those actually measured may play a significant role in the clinical late-phase
      reaction.

PMID- 11591189
TI  - Prevention of new sensitizations in asthmatic children monosensitized to house
      dust mite by specific immunotherapy. A six-year follow-up study.
AB  - BACKGROUND: Specific immunotherapy (SIT) is a recognized way of treating IgE
      mediated respiratory diseases. The clinical outcome is usually better in allergic
      children than in adults. OBJECTIVE: To increase our knowledge of the ability of
      SIT to prevent the onset of new sensitizations in monosensitized subjects, so far
      poorly documented. METHODS: 134 children (age range 5-8 years), who had
      intermittent asthma with or without rhinitis, with single sensitization to mite
      allergen (skin prick test and serum-specific IgE), were enrolled. SIT was
      proposed to all the children's parents, but was accepted by only 75 of them (SIT
      Group). The remaining 63 children were treated with medication only, and were
      considered the Control Group. Injective SIT with mite mix was administered to the
      SIT Group during the first three years and all patients were followed for a total
      of 6 years. All patients were checked for allergic sensitization(s) by skin prick
      test and serum-specific IgE every year until the end of the follow-up period.
      RESULTS: Both groups were comparable in terms of age, sex and disease
      characteristics. 123 children completed the follow-up study. At the end of the
      study, 52 out of 69 children (75.4%) in the SIT Group showed no new
      sensitization, compared to 18 out of 54 children (33.3%) in the Control Group (P
      < 0.0002). Parietaria, Gramineae and Olea were the most common allergens
      responsible for the new sensitization(s). CONCLUSIONS: According to our data, SIT
      may prevent the onset of new sensitizations in children with respiratory symptoms
      monosensitized to house dust mite (HDM).

PMID- 11591188
TI  - An open audit of montelukast, a leukotriene receptor antagonist, in nasal
      polyposis associated with asthma.
AB  - BACKGROUND: Nasal polyposis occurs frequently in patients with intrinsic asthma,
      especially in those who are aspirin sensitive. It can be difficult to treat
      effectively, even with surgery and regular topical intranasal corticosteroids
      many patients are still symptomatic. OBJECTIVE: To investigate the response to
      montelukast, a leukotriene D4 receptor antagonist, as an add-on therapy to
      topical and inhaled corticosteroids in patients, both aspirin sensitive (AS) and
      aspirin tolerant (AT), with nasal polyposis and asthma. METHODS: Nasal polyposis
      symptoms were assessed by visual analogue scales; nasal polyps were assessed by
      nasendoscopy and via the measurement of nasal volumes by acoustic rhinometry. The
      nasal airway was assessed by nasal inspiratory peakflow (NIPF). Asthma was
      monitored using symptom scores and peak expiratory flow measurements. Aspirin
      sensitivity was assessed by history together with intranasal lysine aspirin
      challenge. Upper and lower airway nitric oxide measurements were made before and
      during treatment. RESULTS: Clinical subjective improvement in nasal polyposis
      occurred in 64% AT (P < 0.01), patients and 50% AS patients (P > 0.05); asthma
      improvement in 87% AT and 61% AS patients (P < 0.05 for both). Objective changes
      in peak flow occurred only in AT patients (P < 0.05). Acoustic rhinometry, nasal
      inspiratory peak flow and nitric oxide levels did not change significantly in any
      group, however, correlations were seen between nitric oxide levels and polyp
      scores and between nitric oxide levels and acoustic rhinometry changes.
      Improvement on montelukast therapy was not associated with any of the following
      variables: age, sex, skin prick test positivity, disease duration or aspirin
      sensitivity. (P > 0.05 for all). CONCLUSION: The findings are consistent with a
      subgroup of nasal polyps/asthma patients in whom leukotriene receptor antagonists
      are effective. This is not related to aspirin sensitivity. Further placebo
      controlled studies need to be undertaken.

PMID- 11591190
TI  - T cell involvement in cutaneous drug eruptions.
AB  - BACKGROUND: The most frequent side-effects of drug therapy are skin eruptions.
      Their pathomechanism is rather unclear. OBJECTIVE: In this prospective study we
      investigated the T cell activation and drug specificity in different forms of
      drug-induced exanthemas from 22 patients. METHODS: During acute drug allergy,
      liver parameters and T cell subset activation in the circulation (up-regulation
      of CD25 and HLA-DR) were evaluated and skin biopsies of the acute lesion
      performed. After recovery, the causative drug was identified by lymphocyte
      transformation (LTT) and scratch-patch tests. RESULTS: Seventeen of 22 (17/22)
      patients had maculo-papular exanthema, 4/22 bullous exanthema and 1/22 urticaria.
      The causative drugs were mainly antibiotics, anti-epileptics and anti
      hypertensives. Up-regulation of HLA-DR on circulating CD4(+) and/or CD8(+) T
      cells was detected in 17 patients, being most marked in patients with bullous
      reactions or hepatic involvement. The LTT was positive in 14/21 analysed and the
      patch test in 7/15. All patients showed lymphocytic infiltration in the skin
      biopsy of the acute lesion. Generally CD4(+) T cells dominated; a higher
      percentage of circulating CD8(+) T cells was found in patients with bullous skin
      reactions or hepatic involvement. CONCLUSION: Our data demonstrate activation and
      drug specificity of T cells in drug-induced skin eruptions. A predominant CD8(+)
      T cell activation leads to more severe (bullous) skin symptoms or liver
      involvement, while predominant activation of CD4(+) cells elicits mainly maculo
      papular reactions.

PMID- 11591192
TI  - The interaction of the polymorphisms in transporter of antigen peptides (TAP) and
      lymphotoxin alpha (LT-alpha) genes and atopic diseases in the Czech population.
AB  - BACKGROUND: Transporter antigen peptide gene (TAP) products are involved in
      antigen processing. These genes, inducible by interferon gamma, as well as
      lymphotoxin alpha (LT-alpha), are located in the HLA region. Their involvement in
      immune response regulation makes them candidate atopy susceptibility genes.
      OBJECTIVE: This study investigates a possible association between previously
      identified polymorphisms within the TAP-1 and LT-alpha genes and clinically
      manifested atopic diseases in the Czech population. METHODS: Caucasian subjects
      of Czech nationality (n = 427) were included in our study. We examined 184
      healthy controls and 243 patients with histories of atopic asthma, allergic
      rhinitis and atopic dermatitis or their combinations. We used the amplification
      refractory mutation system polymerase chain reaction to determine TAP-1 gene
      polymorphisms. LT-alpha genotypes were determined by PCR and restriction analysis
      by NcoI. RESULTS: No significant differences were found in allele or genotype
      frequencies of the LT-alpha gene, as well as in polymorphisms for Val-->Ile at
      codon 333 and Gly-->Asp at codon 637 in the TAP-1 gene between controls and
      patients. However, analysis of the concurrence of the double genotypes of the TAP
      1 polymorphism at codon 333 and the LT-alpha genes showed differences between
      controls and atopic patients (P < 0.02). CONCLUSION: Several reports have
      indicated that different HLA products and genes may be risk factors for or
      protective factors against the development of atopy. We report no association
      between polymorphisms in the LT-alpha and TAP-1 genes alone and atopic diseases
      in the central Europe Caucasian (Czech) population, but there was an interesting
      interaction between the TAP333 and LT-alpha polymorphisms.

PMID- 11591191
TI  - Factors related to allergic sensitization to aeroallergens in a cross-sectional
      study in adults: The Copenhagen Allergy Study.
AB  - BACKGROUND: The factors underlying recent increases in the prevalence of
      respiratory allergy are largely unknown. OBJECTIVE: To assess the association
      between allergic sensitization and several lifestyle/environmental factors.
      METHODS: A cross-sectional population-based study of 15-69-year-olds in
      Copenhagen was carried out in 1990. The participation rate was 77.5% (1112/1435).
      Different lifestyle/environmental factors (explanatory variables) were defined
      based on questionnaire data. Dependent (outcome) variables were skin prick test
      (SPT) positivity or specific IgE positivity to common aeroallergens. Explanatory
      variables associated with outcome in univariate analysis (P < 0.25) were selected
      for multivariate analysis. Subsequently, a final model for each dependent
      variable was obtained by stepwise regression analysis (cut-off for entry/removal
      of variables: P < 0.1). RESULTS: Male sex, young age, low number of siblings, a
      positive family history of hay fever and never smoking, were independently
      associated with both SPT positivity and specific IgE positivity. Furthermore, SPT
      positivity was positively associated with alcohol consumption (dose-response
      relationship only), and negatively associated with previous keeping of a dog in
      the household. The association between alcohol consumption and SPT positivity was
      mainly due to the consumption of wine and remained after adjustment for
      educational level. Specific IgE positivity was furthermore associated with body
      mass index with no apparent dose-response relationship. CONCLUSION: Being male,
      young age, a positive family history of hayfever, low number of siblings and
      never smoking, were independently associated with allergic sensitization. In
      addition, the results indicated a possible relationship of alcohol consumption,
      body mass index and previous keeping of a dog in the household to allergic
      sensitization. There is a need for prospective studies of risk factors for
      respiratory allergy.

PMID- 11591193
TI  - Human mast cell progenitors in peripheral blood from atopic subjects with high
      IgE levels.
AB  - BACKGROUND: It remains unclear whether the number of circulating mast cell
      progenitors is increased in patients with atopic diseases. Distinct genotypes are
      reported to affect mast cell/basophil activation. OBJECTIVE: We compared the
      number and function of mast cell progenitors present in the peripheral blood from
      donors with normal IgE (IgE < 400 U/mL) and those with atopic dermatitis
      accompanied by high serum IgE (IgE > 5000 U/mL). METHODS: Purified peripheral
      blood cells were cultured in serum-free methylcellulose containing stem cell
      factor (SCF), IL-6 plus IL-3. Fresh methylcellulose containing the cytokines was
      layered over every 2 weeks. The cultured mast cells were retrieved from the
      methylcellulose and were functionally analysed. RESULTS: Mast cell colonies were
      distinguished at 6 weeks of culture as other colony types had been degenerated.
      The number of mast cell colony-forming cells varied depending on donors and was
      not significantly increased in peripheral blood from the hyper-IgE atopic
      patients. A significant inversed correlation was found between the number of mast
      cells per one colony and the ages of donors. The cultured mast cells derived from
      atopic patients and those from normal IgE donors equally expressed Fc epsilon RI
      and released histamine through Fc epsilon RI, although IL-4 priming in vitro
      markedly enhanced the function of mast cells regardless of donors. CONCLUSIONS:
      These results indicate that the number of circulating mast cell progenitors may
      be regulated by unknown individual factors unrelated to IgE levels. Mast cell
      function may be regulated largely by environmental factors, such as IL-4, but not
      determined by their progenitors' genotypes.

PMID- 11591194
TI  - Local increase in the number of mast cells and expression of nerve growth factor
      in the bronchus of asthmatic patients after repeated inhalation of allergen at
      low-dose.
AB  - BACKGROUND: Repeated inhalation of allergen at low-dose induces an increase in
      bronchial hyper-responsiveness, without any associated symptom. The concomitant
      events in the bronchus have not been described. OBJECTIVE: We have studied the
      dynamic number of mast cells in the airways of patients with mild asthma before
      and after repeated inhalation of allergen at low-dose and the expression of nerve
      growth factor (NGF), which is reported to promote growth and survival of mast
      cells. METHODS: Twelve patients with mild asthma to cat allergen were enrolled at
      random in a blind placebo-controlled study, and submitted to repeated low-dose
      allergen exposure (1/5 of the provocative dose). Mast cells were immunolocalized
      using an antibody against mast cell tryptase. NGF and its high affinity receptor,
      TrkA, were immunolocalized using anti-NGF and anti-TrkA antibodies, respectively.
      NGF mRNA was quantified by competitive polymerase chain reaction (PCR) after
      reverse transcription of total RNA extracted from bronchial biopsy. NGF protein
      levels were measured by ELISA in bronchoalveolar lavage (BAL) fluid. RESULTS:
      Bronchial mast cell number was increased significantly after allergen exposure as
      compared with before. NGF expression in the bronchus was immunolocalized mainly
      to epithelial cells, but also to fibroblasts, blood vessels, and a few
      infiltrated cells. NGF mRNA levels in bronchial biopsies were increased
      significantly after allergen exposure. The high affinity receptor for NGF, TrkA,
      was immunolocalized to the infiltrated mast cell membrane. CONCLUSION: Our study
      shows that the increase in the number of mast cells and in the expression of NGF
      induced by allergen exposure in the bronchus of asthmatic patients is occurring
      before the onset of symptoms. In addition, our finding of the presence of the
      TrkA receptor on the membrane of the infiltrated mast cell in situ brings
      evidence of the mast cell as a target cell for the growth factor activity of NGF
      in the airways in asthma.

PMID- 11591195
TI  - Immuno-regulatory cytokines in asthma: IL-15 and IL-13 in induced sputum.
AB  - BACKGROUND: The importance of Th2-type lymphocyte function in asthmatic airway
      inflammation is well recognized, but less is known about the factors which
      regulate the function of these lymphocytes in asthma. The macrophage-derived
      cytokine, interleukin (IL)-15 has a number of T cell regulatory properties which
      might be of relevance to asthma and its treatment. OBJECTIVE: The aims were to
      identify and quantify the T cell regulatory cytokine IL-15 in induced sputum
      samples from asthmatic patients, in comparison with IL-13, and to relate the
      levels of these cytokines to treatment with inhaled steroids. METHODS: Induced
      sputum was collected from 16 asthmatics (eight steroid and eight non-steroid
      treated) and eight normal controls. IL-15 and IL-13 levels were measured by
      enzyme-linked immunoassay (ELISA) in sputum. IL-15 levels were also measured in
      sputum cell culture supernatants and localized to specific sputum cells by immuno
      cytochemistry. RESULTS: IL-15 levels were increased and IL-13 levels were
      decreased in sputum fluid from steroid-treated compared with non-steroid-treated
      asthmatics. IL-15 was localized specifically to macrophages and the proportion of
      these cells expressing IL-15 correlated with sputum fluid IL-15 and IL-15 levels
      in cell culture supernatants, and all were higher in the steroid-treated
      asthmatics. CONCLUSION: IL-15 and IL-13 production appears to be reciprocally
      regulated by steroid therapy in asthma patients. The steroid-associated increase
      in IL-15 may regulate a fundamental shift away from an inflammatory Th2-type
      environment in asthma and may be an essential component of the cytokine
      modulation underlying the therapeutic benefit of corticosteroids in this
      condition.

PMID- 11591196
TI  - Difference in exposure to airborne major rat allergen (Rat n 1) and to endotoxin
      in rat quarters according to tasks.
AB  - Endotoxins found in occupational settings constitute a risk factor in the
      severity of respiratory allergic symptoms. OBJECTIVES: To assess the airborne
      concentrations of major rat allergen (Rat n 1) and endotoxin under various
      circumstances. METHODS: We took 483 airborne samples from 12 sites: 114
      individual samples for endotoxin measurements and 113 for Rat n 1, from 38
      workers (nine animal technicians, nine laboratory technicians, nine scientists
      and 11 students); and 256 static samples in rat rooms and experimental rooms,
      with or without disturbance, for simultaneous endotoxin and Rat n 1 measurements.
      Rat n 1 was measured with a two-site monoclonal ELISA and endotoxins with the
      Limulus method. RESULTS: Airborne Rat n 1 and endotoxin were significantly higher
      in rat rooms than in experimental rooms. Animal technicians had the greatest
      exposure to both Rat n 1 and endotoxin. Cage cleaning and rat feeding induced the
      highest exposure to Rat n 1 and endotoxin. Furthermore, we observed no
      significant difference in endotoxin exposure between researchers with or without
      rat contact during the sample period. There was no correlation between the number
      of rats present and airborne endotoxin concentrations. CONCLUSIONS: Exposure to
      airborne Rat n 1 and endotoxin is higher during cleaning and feeding tasks than
      during any other task, we feel that a major source of both is contaminated
      bedding that becomes airborne during disturbance.

PMID- 11591197
TI  - IgE binding components in Tetranychus urticae and Panonychus ulmi-derived crude
      extracts and their cross-reactivity with domestic mites.
AB  - BACKGROUND: Recent investigation has revealed that spider mites such as
      Tetranychus urticae and Panonychus ulmi are important allergens in the
      development of occupational asthma among apple farmers. OBJECTIVE: To evaluate
      IgE binding components in T. urticae and P. ulmi-derived crude extracts and their
      cross-reactivity with Panonychus citri, Tyrophagus putrescentiae and
      Dermatophagoides pteronyssinus in apple cultivating farmers. METHODS: Thirty-one
      apple farmers with positive skin responses to T. urticae or P. ulmi were randomly
      recruited, and specific IgE levels in their sera were measured using ELISA. Cross
      reactivity was evaluated by ELISA inhibition. IgE binding components were
      evaluated by IgE immunoblotting. RESULTS: A total of 11 IgE binding components in
      T. urticae and 10 in P. ulmi were found. Among them, the 17 kDa, 27 kDa, 33 kDa,
      37 kDa, 41 kDa, 56 kDa, and 75 kDa allergens in T. urticae, and the 33 kDa, 41
      kDa, and 51 kDa allergens in P. ulmi were identified as dominant allergens. T.
      urticae-specific IgE binding was completely inhibited by 100 microg/mL of T.
      urticae (99.7%), but only partially inhibited by P. citri (83.0%), P. ulmi
      (71.6%), T. putrescentiae (69.7%), and D. pternonyssinus (60.1%). P. ulmi
      specific IgE binding was completely inhibited by additions of P. citri (92.3%)
      and P. ulmi (91.2%), but only partially inhibited by the addition of T. urticae
      (61.5%), T. putrescentiae (57.7%), and D. pteronyssinus (54.4%). CONCLUSION:
      There were seven dominant allergens found in T. urticae and three in P. ulmi. T.
      urticae- and P. ulmi-specific IgE bindings were partially inhibited by crude
      extracts derived from D. pteronyssinus and T. putrescentiae.

PMID- 11591198
TI  - Validity of specific IgE antibodies in children with egg allergy.
AB  - BACKGROUND: The demonstration of specific IgE antibodies to egg supports the
      existence of allergy to this food, but a correct diagnosis can only be obtained
      after a challenge test. Several studies have assessed different cut-off points in
      the level of these antibodies as predictors of clinical reactivity. OBJECTIVE:
      Validation of the specific IgE antibodies measured by the CAP System Fluorescence
      enzyme immunoassay (FEIA) technique in the diagnosis of egg allergy in children
      under 2 years of age. METHODS: A prospective study of 81 children with suspected
      egg allergy was performed. Specific IgE antibodies was quantified for egg white,
      egg yolk, ovoalbumin and ovomucoid. The diagnostic challenge test was carried out
      following the previously established criteria. The validity of the specific IgE
      antibodies was analysed using children with a negative diagnostic challenge test
      as control group. RESULTS: The prevalence of egg allergy in the group studied was
      79% and egg white was the allergen that showed the greatest diagnostic efficacy.
      The sensitivity and positive predictive value of the prick test and of the CAP to
      egg white were excellent and the specificity and the negative predictive value
      had lower values. A level of > or = 0.35 KU(A)/L for specific IgE antibodies to
      egg white predicted the existence of reaction in 94% of the cases. CONCLUSIONS:
      Quantification of the specific IgE antibodies to egg white is useful in the
      diagnosis of egg allergy. In children under 2 years of age with a background of
      immediate hypersensitivity after egg ingestion and presence of specific IgE
      antibodies to egg white of > or = 0.35 KU(A)/L, diagnostic challenge test is not
      necessary to establish the diagnosis of allergy to this food.

PMID- 11591202
TI  - Epidemiology of Clostridium difficile-associated infections.
AB  - Clostridium difficile is responsible for 15-25% of cases of antibiotic-associated
      diarrhea (AAD) and for virtually all cases of antibiotic-associated
      pseudomembranous colitis (PMC). This anaerobic bacterium has been identified as
      the leading cause of nosocomial infectious diarrhea in adults and can be
      responsible for large outbreaks. Nosocomial C. difficile infection results in an
      increased length of stay in hospital ranging from 8 to 21 days. Risk factors for
      C. difficile-associated diarrhea include antimicrobial therapy, older age (>65
      years), antineoplastic chemotherapy and length of hospital stay. Other
      interventions with high risk associations are enemas, nasogastric tubes,
      gastrointestinal surgery and antiperistaltic drugs. Prospective studies have
      shown that nosocomial transmission of C. difficile is frequent but often remains
      asymptomatic. Patients can be contaminated from environmental surfaces, shared
      instrumentation, hospital personnel hands and infected roommates. Once an
      outbreak starts, C. difficile may be spread rapidly throughout the hospital
      environment where spores may persist for months. Measures that are effective in
      reducing incidence of C. difficile infections and cross-infection include: (i) an
      accurate and rapid diagnosis, (ii) appropriate treatment, (iii) implementation of
      enteric precautions for symptomatic patients, (iv) reinforcement of hand-washing,
      (v) daily environmental disinfection, and (vi) a restrictive antibiotic policy.
      C. difficile is a common cause of infectious diarrhea and should be therefore
      systematically investigated in patients with nosocomial diarrhea.

PMID- 11591199
TI  - Heme oxygenase-1 (HO-1) protein induction in a mouse model of asthma.
AB  - BACKGROUND AND OBJECTIVE: Carbon monoxide (CO) is known to be present in
      measurable quantities in the exhalation of asthmatic patients. Corticosteroid
      treatment resulted in a decrease in exhaled CO levels in asthmatic patients,
      raising the possibility that an increase in exhaled CO concentration reflects
      inflammation of the asthmatic airway. Heme oxygenase-1 (HO-1) protein, also
      called HSP32, is the rate-limiting enzyme in the catabolism of heme to
      biliverdin, free iron and CO. However, it is unknown whether an expression of HO
      1 within the lung tissue is related to allergic airway inflammation. We studied
      the expression of HO-1 in lung tissue and bronchoalveolar lavage cells in a mouse
      model of asthma. METHODS: Ovalbumin (OVA)-sensitized C57BL/6 mice were challenged
      with aerosolized OVA. HO-1 positive cells were identified by immunostaining in
      lung tissue and bronchoalveolar lavage fluid (BALF) after the challenge. RESULTS:
      HO-1 positive cell numbers increased in the subepithelium of the bronchi after
      OVA challenge. In cytospin preparations from BALF after OVA challenge, HO-1 was
      localized to alveolar macrophages. Inside the macrophages, HO-1 reactivity was
      expressed in the cytoplasm, and the perinuclear region in particular. CONCLUSION:
      The expression of HO-1 is increased within the lung tissue in allergic airway
      inflammation. Measurement of HO-1 activity may be clinically useful in the
      management of asthma.

PMID- 11591203
TI  - Laboratory diagnosis of Clostridium difficile disease.
AB  - The laboratory diagnosis of Clostridium difficile-associated disease (CDAD) is
      based on culture and toxin detection in fecal specimens. Culture is performed on
      a commercially available selective media. C. difficile colony morphology is
      typical when viewed under a dissecting microscope. Definitive identification is
      best obtained by gas liquid chromatography. Culture is very sensitive but, when
      used alone without toxin testing, it leads to low specificity and misdiagnosis of
      CDAD when high rates of asymptomatic carriage exist. Toxin detection by a tissue
      culture cytotoxin assay followed by neutralisation with specific antiserum is
      often considered the standard. However, this approach lacks sensitivity and has
      not detected up to 30% of patients with confirmed CDAD. Multiple enzyme
      immunoassays (EIAs) have been introduced by various manufacturers for the
      detection of toxin A alone or for both toxins A and B. Some of these are designed
      to give results in less than 1 h. Comparative studies of EIA kits reported that
      the sensitivity and specificity are slightly lower than cytotoxin assays.
      Toxigenic culture tests C. difficile isolates for toxin production: colonies
      isolated on selective media are tested for in-vitro toxin production either by a
      cytotoxicity assay or by direct EIA. It has higher sensitivity than the
      cytotoxicity assay and equivalent specificity. In the routine laboratory, culture
      and toxin detection should be performed on every specimen and, in culture
      positive and fecal toxin-negative cases, toxigenic cultures should be performed
      on isolated colonies.

PMID- 11591204
TI  - How to detect Clostridium difficile variant strains in a routine laboratory.
AB  - Toxin A-negative, toxin B-positive strains (A-/B+) are the best studied examples
      of Clostridium difficile variant strains. In addition, there are some other
      groups of variant C. difficile strains that produce both toxins (A+/B+) or are
      non-cytotoxic (A-/B-) but differ from the reference strain VPI 10463 in their
      toxin genes. Here we describe two simple methods (amplification of the tcdA gene
      and amplification of the binary toxin gene cdtA) which can be used in rapid
      screening for variant C. difficile strains in collections or in routine
      laboratories.

PMID- 11591205
TI  - The pathogenicity of Clostridium difficile.
AB  - It is now well established that the major virulence factors of C. difficile are
      the two toxins A and B. However, the organism possesses an array of other
      putative virulence factors that may be important for localisation within the
      colon, and in evasion of the immune system. It has been observed that certain
      types of C. difficile are more commonly found causing disease than others, and
      this seems to be independent of toxin production. Is this simply a reflection of
      their abundance in the hospital environment, or is it due to their virulence
      determinants? This review covers our current knowledge of the modes of action of
      toxins A and B at the cellular and molecular level. Many unanswered questions are
      posed that require answers before we can fully understand the pathogenic
      mechanisms of the organism and be in a position to manage better the spectrum of
      diseases it causes.

PMID- 11591206
TI  - Typing of Clostridium difficile.
AB  - Clostridium difficile is primarily recognised as a nosocomially acquired pathogen
      manifesting in gastrointestinal disease subsequent to the patient receiving broad
      spectrum antibiotics. Infection can be sporadic, but outbreaks commonly occur
      within a ward or hospital as a result of cross-infection. Since the 1980s, the
      epidemiology of C. difficile disease has been studied by the application of many
      different typing or fingerprinting methods; these, and the lessons learned, are
      reviewed herein.

PMID- 11591207
TI  - Mathematical modeling of Clostridium difficile infection.
AB  - Clostridium difficile diarrhea is a major cause of morbidity and mortality in
      hospitals. However, the number of cases in an outbreak is usually relatively
      small. This precludes many traditional statistical methods of modeling epidemics.
      Stochastic models are designed to deal with small numbers and are promising
      methods of understanding C. difficile epidemiology. This is illustrated by a
      reversible jump Markov chain Monte Carlo model based on the herd immunity
      hypothesis of C. difficile outbreaks.

PMID- 11591208
TI  - Characteristics of Clostridium difficile strains isolated from asymptomatic
      individuals and from diarrheal patients.
AB  - OBJECTIVES: To characterise genotypes of Clostridium difficile strains isolated
      from asymptomatic individuals and patients with diarrhea. METHODS: Fecal
      specimens from 235 asymptomatic infants <12 months, 76 asymptomatic children 1-11
      years and 132 adult patients with antibiotic-associated and non-antibiotic
      associated diarrhea obtained from Siriraj Hospital, Bangkok from October 1998 to
      April 1999 were examined for C. difficile by cycloserine-cefoxitin-fructose agar
      culture. The presence of the C. difficile toxin A gene was determined by specific
      PCR with the use of primers 5-(CCC AAT AGA AGA TTC AAT ATT AAG CTT)-3 and 5-(GGA
      AGA AAA GAA CTT CTG GCT CAC TCA GGT)-3. All C. difficile isolates were
      subsequently genotyped by pulsed-field gel electrophoresis (PFGE). RESULTS: The
      C. difficile strains were found in 28 (11.9%) asymptomatic infants, 16 (21.1%)
      asymptomatic children and 33 (25%) adult patients. In total, 14 PFGE types and
      eight subtypes designated as types A, B, C, D, E, F, G, H, I, J, K, L, M and N,
      and A1, A2, A3, A4, B1, B2, B3 and E1, respectively, were identified. Only two
      isolates from infants and 18 isolates from adult patients were toxin A gene
      positive by PCR. Both isolates of toxigenic C. difficile were from infants in the
      same ward and were PFGE type B. PFGE type A was the predominant type among all
      toxigenic isolates (12 of 18 isolates) from adult patients. The other PFGE types
      of toxigenic C. difficile found in adult patients were: type A1, one isolate;
      type B, four isolates; and type C, one isolate. Types B2 and D were identified in
      38.5% and 46.2%, respectively, of the toxin A gene-negative isolates of C.
      difficile from infants. CONCLUSIONS: These results revealed the occurrence of
      three distinct clusters from different wards in Siriraj Hospital. The toxigenic
      C. difficile of PFGE type A and related subtypes was a predominant infective
      clone in adult patients, whereas non-toxigenic C. difficile types B2 and D were
      encountered in asymptomatic infants. This information can be useful in
      epidemiologic investigations.

PMID- 11591210
TI  - Clostridium difficile cytotoxin B in adults with diarrhea: a comparison of
      patients treated or not treated with antibiotics prior to infection.
AB  - OBJECTIVE: To study the detection rate of Clostridium difficile cytotoxin B in
      stool specimens from adults with diarrhea as related to previous antimicrobial
      treatment. METHODS: Stool specimens from 802 adult patients with diarrhea and 203
      healthy controls were tested for C. difficile cytotoxin B using a cell
      cytotoxicity assay. Antibiotic susceptibility testing of C. difficile was
      performed with the E test. RESULTS: Of 173 patients treated with antimicrobial
      medication within 5 weeks of onset of diarrhea, 60 (35%) were positive for C.
      difficile cytotoxin B (group A) compared to only 41 (7%) of 629 untreated
      patients (group B) and two of the 203 (1%) healthy controls. Compared to patients
      in group A, patients in group B possessed characteristics not usually connected
      with C. difficile disease. They were generally younger (median age 40 years vs.
      73 years), had been hospitalized less frequently (10% vs. 67%), had more often
      travelled abroad within the previous 2 weeks (46% vs. 1%), and more often had
      multiple enteropathogens (41% vs. 3%). Minimal inhibitory concentrations for
      vancomycin, metronidazole and fucidic acid to C. difficile isolates ranged from
      0.5 to 4 mg/L, from 0.125 to 256 mg/L and 0.25 to 4 mg/L, respectively.
      CONCLUSIONS: The detection rate of C. difficile cytotoxin B in patients with
      diarrhea, not associated with antibiotic treatment, is comparable to that in
      healthy control subjects. It probably merely reflects a carrier state without
      clinical significance.

PMID- 11591209
TI  - Clonal dissemination of a toxin-A-negative/toxin-B-positive Clostridium difficile
      strain from patients with antibiotic-associated diarrhea in Poland.
AB  - OBJECTIVE: To determine the incidence of toxin-A-negative/toxin-B-positive
      Clostridium difficile strains and their genetic relatedness in the feces of
      patients suffering from antibiotic-associated diarrhea (AAD) in Polish hospitals.
      METHODS: C. difficile strains were cultured from patients' stool samples. The
      present study characterises these strains with respect to their cytopathogenicity
      on McCoy cells and the absence of toxin A despite a functional toxin B as
      determined with commercial test kits (Culturette Brand Toxin CD-TCD toxin A test
      and C. difficile Tox A/B test). In addition, PCR using different primer pairs
      aiming at non-repeating or repeating regions of the toxin A and B genes were used
      to confirm the findings. All toxin A(-)B(+) strains were genetically
      characterised by random amplification of polymorphic DNA (RAPD) analysis, PCR
      ribotyping and, in part, pulsed-field gel electrophoresis (PFGE) of DNA
      macrorestriction fragments. RESULTS: We here present the presence of 17 toxin A(
      )B(+) strains among 159 C. difficile strains (11%) isolated from fecal samples
      from 413 patients with antibiotic-associated diarrhea. All 17 strains possessed
      the toxin B gene, demonstrated a cytopathogenic effect on the McCoy cells, and
      were positive in the Tox A/B test. Molecular typing of these 17 C. difficile
      strains revealed that 7 of 17 (41%) toxin A(-)/B(+) C. difficile strains could
      not be discriminated. It appeared that these strains had a genotype that could
      not be distinguished from that of a Japanese control strain. CONCLUSION: Our
      observations imply that a particular genotype of toxin A(-)B(+) C. difficile has
      spread extensively, not only in Poland but possibly even worldwide.

PMID- 11591211
TI  - Clinical microbiological case: a heart transplant recipient with diarrhea and
      abdominal pain. Recurring C. difficile infection.

PMID- 11591212
TI  - Extra-intestinal infections caused by Clostridium difficile.
AB  - The objective of this paper was to investigate the incidence of extra-intestinal
      infections caused by Clostridium difficile. During a 10-year period, the
      microbiology laboratory of our institution isolated 2034 isolates of C.
      difficile. Of the 2034 isolates, 21 (1.08%) were obtained from extra-intestinal
      sources. This represents an incidence of extra-intestinal isolation of four cases
      per 100 000 admissions. We were able to review the records of 17 patients for our
      study. The isolates in 12 patients were obtained from structures or fluids
      anatomically close to the colon and included the following infections:
      peritonitis in five cases (three primary and two secondary), intra-abdominal
      abscesses in three patients and abdominal wound infections in four cases. The
      infections in the other five patients were not in the anatomic vicinity of the
      colon. They included one case with a brain abscess, two episodes of bacteremia
      and two cases of foot infections (one chronic osteomyelitis). In all but one
      case, C. difficile isolation was obtained as part of a polymicrobial flora. The
      isolates were frequently non-toxigenic and the extra-intestinal infections
      occurred without concomitant diarrhea or prior anti-microbial therapy. Out of the
      17 patients, eight died and nine survived. Death could not be directly attributed
      to C. difficile in any of the cases. The isolation of C. difficile outside the
      intestinal tract is very uncommon. Its clinical significance should be
      interpreted with caution.

PMID- 11591214
TI  - FOUNTAIN: a JAVA open-source package to assist large sequencing projects.
AB  - BACKGROUND: Better automation, lower cost per reaction and a heightened interest
      in comparative genomics has led to a dramatic increase in DNA sequencing
      activities. Although the large sequencing projects of specialized centers are
      supported by in-house bioinformatics groups, many smaller laboratories face
      difficulties managing the appropriate processing and storage of their sequencing
      output. The challenges include documentation of clones, templates and sequencing
      reactions, and the storage, annotation and analysis of the large number of
      generated sequences. RESULTS: We describe here a new program, named FOUNTAIN, for
      the management of large sequencing projects http://genetics.hpi.uni
      hamburg.de/FOUNTAIN.html. FOUNTAIN uses the JAVA computer language and data
      storage in a relational database. Starting with a collection of sequencing
      objects (clones), the program generates and stores information related to the
      different stages of the sequencing project using a web browser interface for user
      input. The generated sequences are subsequently imported and annotated based on
      BLAST searches against the public databases. In addition, simple algorithms to
      cluster sequences and determine putative polymorphic positions are implemented.
      CONCLUSIONS: A simple, but flexible and scalable software package is presented to
      facilitate data generation and storage for large sequencing projects. Open source
      and largely platform and database independent, we wish FOUNTAIN to be improved
      and extended in a community effort.

PMID- 11591215
TI  - Cell adhesion and signaling on the fibronectin 1st type III repeat; requisite
      roles for cell surface proteoglycans and integrins.
AB  - BACKGROUND: The first type III repeat of fibronectin is known to be involved in
      fibronectin matrix assembly, and recombinant proteins from this type III repeat
      can inhibit cell proliferation, tumor metastasis and angiogenesis. We have
      analyzed the way rat aortic smooth muscle cells (RASMCs) interact with a
      recombinant protein encompassing a C-terminal portion of the first type III
      repeat of fibronectin (protein III1-C). RESULTS: Cells are able to adhere to and
      spread on III1-C coated on a dish. Both beta1 integrins and cell surface heparan
      sulfate proteoglycans serve as receptors for III1-C. For example, cell attachment
      to III1-C is partially inhibited by agents that block beta1 integrins or by
      heparin. Complete inhibition of cell attachment is seen only when integrin
      blocking agents are combined with heparin. Affinity chromatography revealed the
      binding of proteins that likely represent the integrin beta1 and alpha5 submits
      to a III1-C column. Cell adhesion to III1-C results in robust ERK1/2 activation
      that is blocked by integrin-blocking agents. In addition, cell adhesion to III1-C
      and ERK1/2 activation by III1-C are both inhibited by heparan sulfate but not by
      chondroitin sulfate. Moreover, heparitinase treatment, but not chondroitinase
      treatment of RASMCs results in reduced cell adhesion and ERK1/2 activation.
      Affinity chromatography experiments demonstrated that 35SO4-labeled cell surface
      heparan sulfate proteoglycans bound specifically to III1-C. CONCLUSIONS: The
      results suggest that the 1st type III repeat of fibronectin contains a previously
      unrecognized cell adhesion domain that stimulates robust ERK1/2 activation in
      RASMCs. Cells interact with this domain through cell surface heparan sulfate
      proteoglycans and integrins, and both classes of receptors are required for
      optimal cell adhesion and ERK1/2 activation.

PMID- 11591216
TI  - Evolution and phylogeny of insect endogenous retroviruses.
AB  - BACKGROUND: The genome of invertebrates is rich in retroelements which are
      structurally reminiscent of the retroviruses of vertebrates. Those containing
      three open reading frames (ORFs), including an env-like gene, may well be
      considered as endogenous retroviruses. Further support to this similarity has
      been provided by the ability of the env-like gene of DmeGypV (the Gypsy
      endogenous retrovirus of Drosophila melanogaster) to promote infection of
      Drosophila cells by a pseudotyped vertebrate retrovirus vector. RESULTS: To gain
      insights into their evolutionary story, a sample of thirteen insect endogenous
      retroviruses, which represents the largest sample analysed until now, was studied
      by computer-assisted comparison of the translated products of their gag, pol and
      env genes, as well as their LTR structural features. We found that the three
      phylogenetic trees based respectively on Gag, Pol and Env common motifs are
      congruent, which suggest a monophyletic origin for these elements. CONCLUSIONS:
      We showed that most of the insect endogenous retroviruses belong to a major clade
      group which can be further divided into two main subgroups which also differ by
      the sequence of their primer binding sites (PBS). We propose to name IERV-K and
      IERV-S these two major subgroups of Insect Endogenous Retro Viruses (or Insect
      ERrantiVirus, according to the ICTV nomenclature) which respectively use Lys and
      Ser tRNAs to prime reverse transcription.

PMID- 11591218
TI  - In vivo involvement of polymorphonuclear neutrophils in Leishmania infantum
      infection.
AB  - BACKGROUND: The role of lymphocytes in the specific defence against L. infantum
      has been well established, but the part played by polynuclear neutrophil (PN)
      cells in controlling visceral leishmaniasis was much less studied. In this report
      we examine in vivo the participation of PN in early and late phases of infection
      by L. infantum. RESULTS: Promastigote phagocytosis and killing occurs very early
      after infection, as demonstrated by electron microscopy analyses which show in
      BALB/c mouse spleen, but not in liver, numerous PN harbouring ultrastructurally
      degraded parasites. It is shown, using mAb RB6-8C5 directed against mature mouse
      granulocytes, that in chronically infected mice, long-term PN depletion did not
      enhance parasite counts neither in liver nor in spleen, indicating that these
      cells are not involved in the late phase of L. infantum infection. In acute stage
      of infection, in mouse liver, where L. infantum load is initially larger than
      that in spleen but resolves spontaneously, there was no significant effect of
      neutrophils depletion. By contrast, early in infection the neutrophil cells
      crucially contributed to parasite killing in spleen, since PN depletion,
      performed before and up to 7 days after the parasite inoculation, resulted in a
      ten-fold increase of parasite burden. CONCLUSIONS: Taken together these data show
      that neutrophil cells contribute to the early control of the parasite growth in
      spleen but not in liver and that these cells have no significant effect late in
      infection in either of these target organs.

PMID- 11591219
TI  - Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice.
AB  - BACKGROUND: The presynaptic protein alpha-synuclein is involved in a range of
      neurodegenerative diseases. Here we analyze potential compensatory mechanisms in
      alpha-synuclein null mutant mice. Furthermore, the findings reveal problems that
      may be associated with inbred mouse strains. RESULTS: Expression profiling by
      cDNA array technology in a transgenic mouse model revealed striking differences
      only in the expression level of alpha-synuclein. This was caused by a chromosomal
      deletion of the alpha-synuclein locus in the C57BL/6J inbred strain used for
      backcrossing. However, the deletion is only present in a subpopulation of
      C57BL/6J mice, namely animals from Harlan. No other genes are known to be
      affected by the deletion, which is estimated to be smaller than 2 cM. We propose
      to name this strain C57BL/6S. C57BL/6S animals appear phenotypically normal. They
      show no upregulation of beta-synuclein or gamma-synuclein, excluding a
      compensatory mechanism. Also, the expression of synphilin-1 was unaffected.
      CONCLUSIONS: The C57BL/6S strain should help in the understanding of the
      physiological function of alpha-synuclein and its involvement in
      synucleinopathies. Also, the findings exemplify unexpected complications that may
      arise during the study of transgenic models or inbred strains, in particular when
      combined with genome wide screening techniques.

PMID- 11591220
TI  - Incomplete evidence: the inadequacy of databases in tracing published adverse
      drug reactions in clinical trials.
AB  - BACKGROUND: We would expect information on adverse drug reactions in randomised
      clinical trials to be easily retrievable from specific searches of electronic
      databases. However, complete retrieval of such information may not be
      straightforward, for two reasons. First, not all clinical drug trials provide
      data on the frequency of adverse effects. Secondly, not all electronic records of
      trials include terms in the abstract or indexing fields that enable us to select
      those with adverse effects data. We have determined how often automated search
      methods, using indexing terms and/or textwords in the title or abstract, would
      fail to retrieve trials with adverse effects data. METHODS: We used a sample set
      of 107 trials known to report frequencies of adverse drug effects, and measured
      the proportion that (i) were not assigned the appropriate adverse effects
      indexing terms in the electronic databases, and (ii) did not contain identifiable
      adverse effects textwords in the title or abstract. RESULTS: Of the 81 trials
      with records on both MEDLINE and EMBASE, 25 were not indexed for adverse effects
      in either database. Twenty-six trials were indexed in one database but not the
      other. Only 66 of the 107 trials reporting adverse effects data mentioned this in
      the abstract or title of the paper. Simultaneous use of textword and indexing
      terms retrieved only 82/107 (77%) papers. CONCLUSIONS: Specific search strategies
      based on adverse effects textwords and indexing terms will fail to identify
      nearly a quarter of trials that report on the rate of drug adverse effects.

PMID- 11591221
TI  - Clinical utility of a nested nucleic acid amplification format in comparison to
      viral culture for the diagnosis of mucosal herpes simplex infection in a
      genitourinary medicine setting.
AB  - BACKGROUND: Nested nucleic acid amplification tests are often thought too
      sensitive or prone to generating false positive results for routine use. The
      current study investigated the specificity and clinical utility of a routine
      multiplex nested assay for mucosal herpetic infections. METHODS: Ninety patients,
      categorised into those clinically diagnosed to (a) have and (b) not have herpetic
      infection, were enrolled. Swabs from oral and ano-genital sites were assayed by
      the nested assay and culture and the results assessed against clinical evaluation
      for diagnosing herpetic infections; cell content was also recorded. RESULTS:
      Twenty-six and 64 patients were thought to (a) have and (b) not have mucosal
      herpetic infection. Taking the clinical evaluation as indicating the presence of
      herpetic infection, the nested polymerase chain reaction and culture had
      respective sensitivities of 19/26 (73%) and 12/26 (46%) (Chi2 p = 0.02). There
      was no significant difference in specificities between nPCR62/64 (97%) and
      culture 63/64 (98%) (Chi2 p = 1.0). Cell content was important for viral
      detection by nPCR (Chi2 p = 0.07) but not culture. Nesting was found necessary
      for sensitivity and did not reduce specificity. Assay under-performance appeared
      related to sub-optimal cell content (20%) but may have reflected clinical over
      diagnosis. The results suggest the need for validating specimen cell quality.
      CONCLUSIONS: This study questions the value of routine laboratory confirmation of
      mucosal herpetic infection. The adoption of a more discriminatory usage of
      laboratory diagnostic facilities for genital herpetic infection, taking account
      of cell content, and restricting it to those cases where it actually affects
      patient management, may be warranted.

PMID- 11591222
TI  - Aseptic meningitis in Germany associated with echovirus type 13.
AB  - BACKGROUND: Echoviruses are the commonest cause of aseptic meningitis. Echovirus
      type 13 which has not been isolated in Germany over a long period of time was the
      predominant enterovirus serotype associated with different local outbreaks of
      aseptic meningitis in Germany in 2000. METHODS: Virus isolation was performed
      from cerebrospinal fluid and stools. In order to study the genetic relationship
      of echovirus type 13 isolates, sequence analysis of a part of VP1 (~300 nt) was
      carried out. Isolates from different geographic regions were compared to each
      other as well as to elder viruses (prototype strain from 1953, four isolates from
      1965-1986). RESULTS: Overall, 55 isolates of echovirus type 13 were obtained from
      different parts of Germany. It was shown that the new isolated strains have a
      very high degree of homology on the nucleotide level (> 98%)) but differ
      significantly from the old strains (76-85%). CONCLUSIONS: a) Rare enterovirus
      serotypes can cause serious illness.b) The molecular drift has also been shown
      for other enterovirus serotypes.

PMID- 11591223
TI  - The efficacy of chemical agents in cleaning and disinfection programs.
AB  - BACKGROUND: Due to the growing number of outbreaks of infection in hospital
      nurseries, it becomes essential to set up a sanitation program that indicates
      that the appropriate chemical agent was chosen for application in the most
      effective way. METHOD: For the purpose of evaluating the efficacy of a chemical
      agent, the minimum inhibitory concentration (MIC) was reached by the classic
      method of successive broth dilutions. The reference bacteria utilized were
      Bacillus subtilis var. globigii ATCC 9372, Bacillus stearothermophilus ATCC 7953,
      Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923. The strains of
      Enterobacter cloacae IAL 1976 (Adolfo Lutz Institute), Serratia marcescens IAL
      1478 and Acinetobactev calcoaceticus IAL 124 (ATCC 19606), were isolated from
      material collected from babies involved in outbreaks of infection in hospital
      nurseries. RESULTS: The MIC intervals, which reduced bacteria populations over 08
      log10, were: 59 to 156 mg/L of quaternarium ammonium compounds (QACs); 63 to
      10000 mg/L of chlorhexidine digluconate; 1375 to 3250 mg/L of glutaraldehyde; 39
      to 246 mg/L of formaldehyde; 43750 to 87500 mg/L of isopropanol or ethanol; 1250
      to 6250 mg/L of iodine in polyvinyl-pyrolidone complexes, 150 to 4491 mg/L of
      chlorine-releasing-agents (CRAs); 469 to 2500 mg/L of hydrogen peroxide; and,
      2310 to 18500 mg/L of peracetic acid. CONCLUSIONS: Chlorhexidine showed non
      inhibitory activity over germinating spores. A. calcoaceticus, was observed to
      show resistance to the majority of the agents tested, followed by E. cloacae and
      S. marcescens.

PMID- 11591224
TI  - Heart rate changes during partial seizures: a study amongst Singaporean patients.
AB  - INTRODUCTION: Studies in Europe and America showed that tachycardia, less often
      bradycardia, frequently accompanied partial seizures in Caucasian patients. We
      determine frequency, magnitude and type of ictal heart rate changes during
      partial seizures in non-Caucasian patients in Singapore. METHODS: Partial
      seizures recorded during routine EEGs performed in a tertiary hospital between
      1995 and 1999 were retrospectively reviewed. All routine EEGs had simultaneous
      ECG recording. Heart rate before and during seizures was determined and
      correlated with epileptogenic focus. Differences in heart rate before and during
      seizures were grouped into 4 types: (1) >10% decrease; (2) -10 to +20% change;
      (3) 20-50% increase; (3) >50% increase. RESULTS: Of the total of 37 partial
      seizures, 18 were left hemisphere (LH), 13 were right hemisphere (RH) and 6 were
      bilateral (BL) in onset. 51% of all seizures showed no significant change in
      heart rate (type 2), 22% had moderate sinus tachycardia (type 3), 11% showed
      severe sinus tachycardia (type 4), while 16% had sinus bradycardia (type 1).
      Asystole was recorded in one seizure. Apart from having more tachycardia in
      bilateral onset seizures, there was no correlation between side of ictal
      discharge and heart rate response. Compared to Caucasian patients, sinus
      tachycardia was considerably less frequent. Frequency of bradycardia was similar
      to those recorded in the literature. CONCLUSIONS: Significant heart rate changes
      during partial seizures were seen in half of Singaporean patients. Although sinus
      tachycardia was the most common heart rate change, the frequency was considerably
      lower compared to Caucasian patients. This might be due to methodological and
      ethnic differences. Rates of bradycardia are similar to those recorded in the
      literature.

PMID- 11591225
TI  - The metal coordination of sCD39 during ATP hydrolysis.
AB  - BACKGROUND: The hydrolysis of ATP and ADP by ecto-nucleoside triphosphate
      diphosphohydrolase 1 (CD39) requires divalent cations, like Ca2+ and Mg2+. In
      spite of considerable work, it is not clear whether divalent cations bind to the
      enzyme in the absence of nucleotide or only as nucleotide-Me+2 complex. Here we
      study the protein ligands for Me+2. RESULTS: When VO2+ was used as a substitute
      for Ca2+, the ATPase activity of soluble CD39 was 25% of that with Ca2+ as
      cofactor. Protein ligands of the VO2+-nucleotide complex bound to the catalytic
      site of soluble CD39 were characterized by electron paramagnetic resonance (EPR)
      spectroscopy. The EPR spectrum contained one species designated T with VO2+
      AMPPNP as ligand. Two species D1 and D2 were observed when VO2+-AMPCP was bound
      to soluble CD39. The results suggest that species D1 and D2 represent the metal
      ADP complexes at the catalytic site of soluble CD39 corresponding to the
      intermediate formed during ATP hydrolysis and the substrate for further
      hydrolysis, respectively. CONCLUSIONS: VO2+ can functionally substitute for Ca2+
      as a cofactor of sCD39, and it produces four different EPR features when bound in
      the presence of different nucleotides or in the absence of nucleotide. The metal
      coordination for each conformation corresponding to each EPR species is proposed,
      and the mechanism of sCD39 catalysis is discussed.

PMID- 11591226
TI  - Mutant loxP vectors for selectable marker recycle and conditional knock-outs.
AB  - BACKGROUND: Gene disruption by targeted integration of transfected constructs
      becomes increasingly popular for studies of gene function. The chicken B cell
      line DT40 has been widely used as a model for gene knock-outs due to its high
      targeted integration activity. Disruption of multiple genes and complementation
      of the phenotypes is, however, restricted by the number of available selectable
      marker genes. It is therefore highly desirable to recycle the selectable markers
      using a site-specific recombination system like Cre/loxP. RESULTS: We constructed
      three plasmid vectors (neoR, puroR and bsr), which carry selectable marker genes
      flanked by two different mutant loxP sites. After stable transfection, the marker
      genes can be excised from the genome by transient induction of Cre recombinase
      expression. This excision converts the two mutant loxP sites to an inactive
      double-mutant loxP. Furthermore we constructed a versatile expression vector to
      clone cDNA expression cassettes between mutant loxP sites. This vector can also
      be used to design knock-out constructs in which the floxed marker gene is
      combined with a cDNA expression cassette. This construct enables gene knock-out
      and complementation in a single step. Gene expression can subsequently be
      terminated by the Cre mediated deletion of the cDNA expression cassette. This
      strategy is powerful for analyzing essential genes, whose disruption brings
      lethality to the mutant cell. CONCLUSIONS: Mutant loxP vectors have been
      developed for the recycle of selectable markers and conditional gene knock-out
      approaches. As the marker and the cDNA expression cassettes are driven by the
      universally active and evolutionary conserved beta-actin promoter, they can be
      used for the selection of stable transfectants in a wide range of cell lines.

PMID- 11591227
TI  - Reporting of adverse drug reactions in randomised controlled trials - a
      systematic survey.
AB  - BACKGROUND: Decisions on treatment are guided, not only by the potential for
      benefit, but also by the nature and severity of adverse drug reactions. However,
      some researchers have found numerous deficiencies in trial reports of adverse
      effects. We sought to confirm these findings by evaluating trials of drug therapy
      published in seven eminent medical journals in 1997. METHODS: Literature review
      to determine whether the definition, recording and reporting of adverse drug
      reactions in clinical trials were in accordance with published recommendations on
      structured reporting. RESULTS: Of the 185 trials reviewed, 25 (14%) made no
      mention of adverse drug reactions. Data in a further 60 (32%) could not be fully
      evaluated, either because numbers were not given for each treatment arm (31
      trials), or because a generic statement was made without full details (29
      trials). When adverse drug reactions such as clinical events or patient symptoms
      were mentioned in the reports, details on how they had been recorded were given
      in only 14/95 (15%) and 18/104 (17%) trials respectively. Of the 86 trials that
      mentioned severity of adverse drug reactions, only 42 (49%) stated how severity
      had been defined. The median amount of space used for safety data in the Results
      and Discussion sections was 5.8%. CONCLUSIONS: Trial reports often failed to
      provide details on how adverse drug reactions were defined or recorded. The
      absence of such methodological information makes comparative evaluation of
      adverse reaction rates potentially unreliable. Authors and journals should adopt
      recommendations on the structured reporting of adverse effects.

PMID- 11591228
TI  - Increasing evidence in favour of mandatory fortification with folic acid.

PMID- 11591229
TI  - Use of water-miscible retinyl palmitate as markers of chylomicrons gives earlier
      peak response of plasma retinyl esters compared with oil-soluble retinyl
      palmitate.
AB  - Delayed peak response of plasma retinyl esters (RE) relative to plasma
      triacylglycerols (TAG) and apolipoprotein (Apo) B-48 responses following a fat
      load supplemented with vitamin A raised doubts about the use of vitamin A to
      label dietary-derived lipids and lipoproteins. The present study compared the use
      of water-miscible and oil-soluble retinyl palmitate (RP) as markers of dietary
      derived lipoproteins in healthy subjects along with the measurements of
      postprandial plasma TAG and ApoB-48 responses to investigate whether the delayed
      peak response observed was due to delayed intestinal output of RE from oil-based
      solutions. Nine healthy female subjects were given a standard test meal
      containing a dose (112 mg) of RP in either water-miscible or oil-soluble form in
      random order, on two separate occasions after a 12 h overnight fast. The results
      showed that the mean plasma RE concentrations reached a peak significantly later
      than mean plasma TAG and ApoB-48 concentrations when oil-soluble RP was consumed,
      whereas plasma RE peaked earlier relative to plasma TAG and ApoB-48 responses
      when water-miscible RP was used. The results suggested a more rapid absorption
      with a significantly higher and earlier peak response of plasma RE when water
      miscible RP was consumed. This was in contrast to the delayed initial appearance
      and later sustained higher concentrations of plasma RE during the late
      postprandial period when oil-soluble RP was consumed. The RE response to the
      water-miscible RP showed better concordance with plasma TAG response than that of
      oil-soluble RP.

PMID- 11591230
TI  - Weaning affects lipoprotein lipase activity and gene expression in adipose
      tissues and in masseter but not in other muscles of the calf.
AB  - The nutritional and physiological modifications that occur during the weaning
      period induce adaptations of tissue metabolism in all mammal species. Among the
      adaptations due to weaning in ruminants, the regulation of lipoprotein lipase
      (LPL) activity, one of the rate-limiting steps of fatty acid utilization by
      tissues, was still unknown. The present study aimed at comparing LPL activity and
      gene expression in the heart, seven skeletal muscles and three adipose tissue
      sites between two groups of seven preruminant (PR) or ruminant (R) calves having
      a similar age (170 d), similar empty body weight (194 kg) at slaughter, and
      similar net energy intake from birth onwards. Triacylglycerol content of adipose
      tissues was 16 % lower in R than in PR calves, This could be partly the result
      from a lower LPL activity (-57 %, ). LPL mRNA levels were also lower in R calves
      (-48 % to -68 %, ) suggesting a pretranslational regulation of LPL activity.
      Activity and mRNA levels of LPL did not differ significantly in the heart and
      skeletal muscles except in the masseter in which LPL activity and mRNA levels
      were higher (+50 % and +120 % respectively, ) in the R calves. Regulation of LPL
      in masseter could be explained by the high contractile activity of this muscle
      after weaning due to solid food chewing. In conclusion, weaning in the calf
      affects LPL activity and expression in adipose tissues, but not in skeletal
      muscles except the masseter.

PMID- 11591231
TI  - Ingestion of insoluble dietary fibre increased zinc and iron absorption and
      restored growth rate and zinc absorption suppressed by dietary phytate in rats.
AB  - We examined the effects of ingestion of five types of insoluble fibre on growth
      and Zn absorption in rats fed a marginally Zn-deficient diet (6.75 mg (0.103
      mmol) Zn/kg diet) with or without added sodium phytate (12.6 mmol/kg diet). The
      types of insoluble fibre tested were corn husks, watermelon skin, yam-bean root
      (Pachyrhizus erosus) and pineapple core, and cellulose was used as a control (100
      g/kg diet). Body-weight gain in the cellulose groups was suppressed by 57 % by
      feeding phytate. Body-weight gain in phytate-fed rats was 80 % greater in the
      watermelon skin fibre and yam-bean root fibre group than that in the cellulose
      group. Zn absorption ratio in the cellulose groups was lowered by 46 and 70 % in
      the first (days 7-10) and second (days 16-19) measurement periods with feeding
      phytate. In the rats fed the phytate-containing diets, Zn absorption ratio in the
      watermelon skin, yam-bean root and pineapple core fibre groups was 140, 80 and 54
      % higher respectively than that in the cellulose group, in the second period. Fe
      absorption was not suppressed by phytate, however, feeding of these three types
      of fibre promoted Fe absorption in rats fed phytate-free diets. The concentration
      of soluble Zn in the caecal contents in the watermelon skin fibre or yam-bean
      root fibre groups was identical to that in the control group in spite of a higher
      short-chain fatty acid concentration and lower pH in the caecum. These findings
      indicate that ingestion of these types of insoluble fibre recovered the growth
      and Zn absorption suppressed by feeding a high level of phytate, and factors
      other than caecal fermentation may also be involved in this effect of insoluble
      fibre.

PMID- 11591232
TI  - The effect of calcium intake on bone composition and bone resorption in the young
      growing rat.
AB  - A low Ca intake by both rats and man increases bone resorption, decreases bone
      mass and increases the risk of osteoporosis. The skeletal effect of high Ca
      intakes is less clear, particularly during periods of bone mineral accrual.
      Twenty-four female 5-week-old rats, Wistar strain, were randomized by weight into
      three groups of eight rats each and fed ad libitum a semi-purified diet
      containing 2 (Ca-restricted), 5 (normal) or 20 (Ca-supplemented) g Ca/kg for 3
      weeks. When compared with the normal Ca diet, urinary Ca excretion was unaffected
      by the dietary restriction of Ca for 3 weeks, but was greater (P<0.001) in Ca
      supplemented rats. Urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) levels
      were significantly greater during weeks 2 (Pyr P<0.05, Dpyr P<0.001) and 3 (Pyr
      P<0.01, Dpyr, P<0.001) of dietary Ca restriction, but were unaffected by Ca
      supplementation. Femoral dry weight and the concentration of Mg and P in femora
      were unaffected by dietary Ca concentration. Femoral Ca concentration was reduced
      (P<0.05) in the Ca-restricted group compared with the other two groups. In
      conclusion, these results suggest that increasing dietary Ca intake, well above
      the recommended level, had no effect on bone mineral composition or bone
      resorption (as assessed with urinary pyridinium crosslinks) in young growing
      female rats. In addition, these results confirm the findings of previous studies
      which have shown that bone Ca content in young growing rats was reduced by
      dietary Ca restriction and that this reduction results, at least in part, from an
      increased rate of bone resorption.

PMID- 11591233
TI  - Changes in piglet tissue composition at birth in response to increasing maternal
      intake of long-chain n-3 polyunsaturated fatty acids are non-linear.
AB  - Addition of marine oils containing long-chain n-3 polyunsaturated fatty acids to
      the diet of pregnant sows may reduce piglet mortality. In previous experiments,
      when marine oils have been fed to pregnant sows, improvements in piglet tissue 22
      : 6n-3 status have been accompanied by potentially undesirable decreases in 20 :
      4n-6. The objective of the present experiment was to establish an amount of
      dietary salmon oil which would enhance piglet 22 : 6n-3 status while minimising
      reductions in 20 : 4n-6. Twenty-four pregnant multiparous sows were used in the
      experiment which began on day 60 of pregnancy (gestation length 115 d). To give
      four diets, salmon oil was added in increasing amounts (0, 5, 10 and 20 g/kg
      diet) to a basal diet; the diets were made isoenergetic by adding palm oil to
      each diet to give a total of 20 g oil/kg diet. Diets were offered to the sows in
      fixed amounts (2.5 kg/d) until parturition. Piglet tissue samples (brain, liver
      and retina) were obtained at birth before consumption of colostrum. The greatest
      increase in piglet tissue 22 : 6n-3 proportions occurred between 0 and 5 g salmon
      oil/kg diet, with only small increases between 10 and 20 g salmon oil/kg diet. In
      contrast, tissue 20 : 4n-6 proportions declined progressively as the amount of
      salmon oil fed to the sow increased. In brain, the change in the value 22 : 6n
      3/22 : 5n-6 was greatest between 0 and 5 g salmon oil/kg diet, whereas in liver
      the value increased linearly with added salmon oil. In addition, piglet brain
      weight (g/kg live weight) increased to a maximum at 10 g salmon oil/kg diet. The
      optimum amount of supplementary salmon oil in the current experiment, defined as
      that which gave the greatest response in brain 22 : 6n-3 proportions with minimum
      reduction in 20 : 4n-6,was 10 g salmon oil/kg diet. This corresponds to an intake
      of approximately 2.4 g 20 : 5n-3 plus 3.6 g 22 : 6n-3/d or 0.6 % digestible
      energy.

PMID- 11591234
TI  - Acute effects of dietary fat composition on postprandial plasma bile acid and
      cholecystokinin concentrations in healthy premenopausal women.
AB  - Bile acids derived from intestinal bacterial metabolism and transported to the
      breast in plasma may influence risk of breast cancer. The purpose of the present
      study was to test the hypothesis that fatty acid chain length and degree of
      unsaturation differ with regard to their influence on the postprandial release of
      cholecystokinin (CCK) and the subsequent increase in plasma bile acid
      concentrations that occur following a meal. A randomized crossover design was
      used to compare five high-fat test meals (50 g fat) with a low-fat test meal (15
      g) on plasma bile acid and CCK concentrations in eighteen healthy premenopausal
      women. The high-fat meals were enriched in oleate or palmitate, or linoleate or
      medium-chain triacylglycerols (MCT) or a blend of oleate and long-chain n-3 fatty
      acids. The postprandial increase in plasma CCK concentration was lower on the MCT
      meal compared with all meals and was greater following the linoleate compared
      with the low-fat meal. Plasma bile acid concentrations increased 2-3-fold
      postprandially but the increase was lower following the MCT meal compared with
      the other meals and was greater on the linoleate meal compared with the low-fat
      meal. The postprandial increases in plasma chenodeoxycholic acid concentration
      showed a trend to rise with increasing unsaturation of the test meal. In
      conclusion, meals rich in linoleate are a potent stimulus for CCK release and
      lead to prolonged elevations of plasma bile acids and meals containing MCT
      inhibit CCK release and the subsequent increase in plasma bile acid
      concentrations.

PMID- 11591235
TI  - Effects of two fermentable carbohydrates (inulin and resistant starch) and their
      combination on calcium and magnesium balance in rats.
AB  - Resistant starch and inulin are complex carbohydrates that are fermented by the
      microflora and known to increase colonic absorption of minerals in animals. The
      fermentation of these substrates in the large bowel to short-chain fatty acids is
      the main reason for this increase in mineral absorption. The purpose of the
      present study was to examine the potential synergistic effect of a combination of
      these two fermentable carbohydrates. For this purpose, thirty-two adult male
      Wistar rats weighing 200 g were used in the present study. The rats were
      distributed into four groups, and fed for 21 d a fibre-free basal purified diet
      or diet containing 100 g inulin, or 150 g resistant starch (raw potato starch)/kg
      diet or a blend of 50 g inulin and 75 g resistant starch/kg diet. After an
      adaptation period of 14 d, the rats were then transferred to metabolic cages and
      dietary intake, faeces and urine were monitored for 5 d. The animals were then
      anaesthetized and caecal Ca and Mg absorption were measured. Finally, the rats
      were killed and blood, caecum and tissues were sampled. Ca and Mg levels were
      assessed in diets, faeces, urine, caecum and plasma by atomic absorption
      spectrometry. Our results confirmed that inulin and resistant starch ingestion
      led to considerable caecal fermentation in the three experimental groups compared
      with the control group diet. Moreover, both carbohydrates significantly increased
      the intestinal absorption and balance of Ca and Mg, without altering the plasma
      level of these two minerals. Interestingly, the combination of the studied
      carbohydrates increased significantly the caecal soluble Ca and Mg
      concentrations, the apparent intestinal absorption and balance of Ca, and non
      significantly the plasma Mg level. In conclusion, a combination of different
      carbohydrates showed synergistic effects on intestinal Ca absorption and balance
      in rats. Further studies with other types of carbohydrate combinations should be
      carried out to extend these findings.

PMID- 11591236
TI  - Increasing viscosity of the intestinal contents alters small intestinal structure
      and intestinal growth, and stimulates proliferation of enterotoxigenic
      Escherichia coli in newly-weaned pigs.
AB  - Sources of viscous soluble fibre, such as barley and oats, have often been
      included in the weaning diet of the pig to accelerate development of the large
      intestine. Inclusion of a non-fermentable, viscous compound, sodium
      carboxymethylcellulose (CMC), in a low-fibre weaning diet was tested to assess
      the influence of digesta viscosity on the gut in the absence of increased
      fermentation. Two CMC sources, of low and high viscosity, were added to cooked
      rice-based diet at 40 g/kg total diet. A third control rice diet did not contain
      any CMC. Diets were fed for 13 d following weaning at 3 weeks of age. Addition of
      CMC to the diet significantly increased the intestinal viscosity of digesta
      within the small (P<0.001) and large (P<0.05) intestine. No simple association
      was found between increases in intestinal viscosity and effects on intestinal
      morphology and whole-body growth. The average empty-body-weight gain and the
      small intestinal villus height increased with low-viscosity CMC, but decreased
      with the high-viscosity CMC group. The full large intestinal weight increased in
      all pigs fed CMC. Dietary CMC (both low- and high-viscosity) increased the
      percentage moisture of digesta and faeces, and was associated with increased
      faecal shedding of enterotoxigenic haemolytic Escherichia coli. Feed ingredients
      in weaning diets that excessively increase the viscosity of the intestinal
      digesta may be detrimental to pig health and production.

PMID- 11591237
TI  - Exposure to purified lignan from flaxseed (Linum usitatissimum) alters bone
      development in female rats.
AB  - Due to the potential oestrogenic effects of secoisolariciresinol diglycoside
      (SDG), the mammalian lignan precursor in flaxseed (Linum usitatissimum), we
      hypothesized that exposure to purified SDG during early life would have a
      positive effect on developing bone. This present study determined whether
      exposure to SDG purified from flaxseed during suckling via mother's milk or
      continuously to adolescence (postnatal day (PND) 50) or adulthood (PND 132)
      increased bone mineral content (BMC) or bone strength in female rat offspring.
      Offspring were exposed to basal diet (BD) or one of two doses of SDG (50S, 100S)
      equivalent to that in a 50 or 100 g flaxseed/kg diet during lactation only or
      through to PND 50 or 132. At PND 50 and 132, femurs were analysed for BMC by dual
      energy X-ray absorptiometry and biomechanical strength by a 3-point bending test.
      Compared with BD group, rats exposed to continuous 50S or 100S diet had stronger
      femurs at PND 50 without changes in BMC. At PND 132 there were no differences in
      femur strength despite the fact that continuous exposure to BD resulted in a
      higher BMC than rats exposed to 100S during lactation only or to 50S or 100S
      during lactation through to adulthood. In conclusion, female rat bone is more
      sensitive to the oestrogen-like action of lignans during early life when
      endogenous levels of sex hormones are low, but by adulthood the improved bone
      strength does not persist. Importantly, exposure to purified lignan does not have
      negative effects on bone strength.

PMID- 11591238
TI  - Liver nitrogen movements during short-term infusion of high levels of ammonia
      into the mesenteric vein of sheep.
AB  - Four 40 kg wethers were used in a crossover design to quantify, by arterio-venous
      procedures, the mass transfer of NH3, urea and amino acids (AAs) across the
      portal-drained viscera and the liver during a 31 min infusion of either 0 (C0) or
      1100 (C1100) micromol NH4HCO3/min into the mesenteric vein. In C1100, hepatic NH3
      extraction remained stable at 1214 micromol/min (1.90 micromol/min per g wet
      liver weight), the capacity for hepatic NH3 removal was exceeded by 654
      micromol/min and the incremental (C1100-C0) urea-N release: NH3 -N removal ratio
      increased progressively, from 0.52 to 0.90. The NH4HCO3 infusion reduced total
      branched-chain AA transfer across the portal-drained viscera and total AA-N and
      lysine extraction by the liver. Hepatic release of glutamate was augmented
      ornithine switched from net release to net removal and net splanchnic release of
      free essential AA (44 micromol/min (sed 9.2), ) and branched-chain AA (33
      micromol/min (sed 2.0), ) were reduced to 0.58 of their basal rate. The study
      showed that conversion of excess NH3 to urea during a short-term hepatic NH3
      overload required no additional contribution of AA-N to ureagenesis; essential AA
      and branched-chain AA supply to non-splanchnic tissues was, however, temporarily
      decreased.

PMID- 11591239
TI  - Low iron status and enhanced insulin sensitivity in lacto-ovo vegetarians.
AB  - The efficacy of insulin in stimulating whole-body glucose disposal (insulin
      sensitivity) was quantified using direct methodology in thirty lacto-ovo
      vegetarians and in thirty meat-eaters. All subjects were adult, lean (BMI <23
      kg/m2), healthy and glucose tolerant. Lacto-ovo vegetarians were more insulin
      sensitive than meat-eaters, with a steady-state plasma glucose (mmol/l) of 4.1
      (95 % CI 3.5, 5.0) v. 6.9 (95 % CI 5.2, 7.5; respectively. In addition, lacto-ovo
      vegetarians had lower body Fe stores, as indicated by a serum ferritin
      concentration (microg/l) of 35 (95 % CI 21, 49) compared with 72 (95 % CI 45,
      100) for meat-eaters To test whether or not Fe status might modulate insulin
      sensitivity, body Fe was lowered by phlebotomy in six male meat-eaters to levels
      similar to that seen in vegetarians, with a resultant approximately 40 %
      enhancement of insulin-mediated glucose disposal Our results demonstrate that
      lacto-ovo vegetarians are more insulin sensitive and have lower Fe stores than
      meat-eaters. In addition, it seems that reduced insulin sensitivity in meat
      eaters is amenable to improvement by reducing body Fe. The latter finding is in
      agreement with results from animal studies where, no matter how induced, Fe
      depletion consistently enhanced glucose disposal.

PMID- 11591240
TI  - Short- and long-term effects of calcium and exercise on bone mineral density in
      ovariectomized rats.
AB  - At the level of prevention of bone mineral loss produced by ovariectomy, the aim
      of the present study was to determine the effect produced by supplementation of
      Ca in the diet and a moderate exercise programme (treadmill), simultaneously or
      separately, in ovariectomized rats, an experimental model of postmenopausal bone
      loss. Female Wistar rats (n 110, 15 weeks old) were divided into five groups: (1)
      OVX, rats ovariectomized at 15 weeks of age, fed a standard diet; (2) SHAM, rats
      sham operated at 15 weeks of age, fed a standard diet; (3) OVX-EX, ovariectomized
      rats, fed a standard diet and performing the established exercise programme; (4)
      OVX-Ca, ovariectomized rats fed a diet supplemented with Ca; (5) OVX-EXCa,
      ovariectomized rats with the exercise programme and diet supplemented with Ca.
      The different treatments were initiated 1 week after ovariectomy and were
      continued for 13 weeks for subgroup 1 and 28 weeks for subgroup 2, to look at the
      interaction of age and time passed from ovariectomy on the treatments. Bone
      mineral density (BMD) was determined, at the end of the study, in the lumbar
      spine (L2, L3 and L4) and in the left femur using a densitometer. Bone turnover
      was also estimated at the end of the study, measuring the serum formation marker
      total alkaline phosphatase (AP) and the resorption marker serum tartrate
      resistant acid phosphatase (TRAP). As expected, OVX rats showed a significant
      decrease (P<0.05) in BMD, more pronounced in subgroup 2, and a significant
      increase in AP and TRAP with regard to their respective SHAM group. The
      simultaneous treatment with Ca and exercise produced the best effects on lumbar
      and femoral BMD of ovariectomized rats, partially avoiding bone loss produced by
      ovariectomy, although it was not able to fully maintain BMD levels of intact
      animals. This combined treatment produced a significant increase in AP, both in
      subgroups 1 and 2, and a decrease in TRAP in subgroup 1, with regard to OVX
      group. The exercise treatment alone was able to produce an increase in BMD with
      regard to OVX group only in subgroup 1 of rats (younger animals and less time
      from ovariectomy), but not in subgroup 2. In agreement with this, there was an
      increase of AP in both subgroups, lower than that observed in animals submitted
      to exercise plus Ca supplement, and a decrease of TRAP in subgroup 1, without
      significant changes in this marker in the older rats. Ca treatment did not
      produce any significant effect on BMD in OVX rats in both subgroups of animals,
      showing a decrease of AP and TRAP levels in the younger animals with no
      significant variations in markers of bone remodelling in the older female rats
      compared with their respective OVX group.

PMID- 11591241
TI  - Dietary intake of folate by adolescents and the potential effect of flour
      fortification with folic acid.
AB  - The UK Department of Health recently recommended that flour be fortified with
      folic acid, at 2400 microg/kg. The objectives of the present paper were: to
      determine the consequence of this on folic acid intake of adolescents; to
      determine the level of fortification necessary to achieve an intake of 400
      microg/d in adolescent girls (the amount recommended periconceptionally); to
      estimate the consequence of fortification on folic acid intake of high flour
      consumers; and to report on folate intake of adolescents. Dietary intake of
      folate and flour were determined by analysis of an existing database of the diets
      of 379 English adolescents. The folic acid intake that would result from white
      flour fortification with folic acid at 2400 microg/kg was determined and the
      level of folic acid fortification necessary to achieve an intake of 400 microg/d
      in girls from this source was also calculated. Without flour fortification, 6.9 %
      of girls failed to reach the UK lower reference nutrient intake for total folate.
      Fortification of white flour with folic acid at 2400 microg/kg would result in an
      additional folic acid intake of 191(sem 6) microg/d in girls. To ensure 97 % of
      girls received 400 microg/d from white flour, white flour would need to be
      fortified at a level of 10 430 microg/kg, resulting in intakes of 1260 microg/d
      from flour in the highest (97.5 centile) female white flour consumers and 1422
      microg/d from flour in the highest (97.5 centile) male white flour consumers.

PMID- 11591242
TI  - Affluent adolescent girls of Delhi: eating and weight concerns.
AB  - Despite a dramatic increase in research on eating-related pathologies, gaps
      remain in our understanding of the factors responsible for the development and
      maintenance of dysfunctional attitudes and behaviour related to weight and eating
      among adolescents. A study was therefore conducted to compare eating and weight
      concerns among underweight, normal-weight and obese affluent adolescent girls in
      New Delhi. The sample comprised fifty underweight, fifty normal-weight and thirty
      obese girls, 16-18 years of age. Information was collected about their body image
      perception, weight concerns and eating attitudes by a well-structured
      questionnaire. Dietary intake was determined by 24 h recall and a food-frequency
      questionnaire. Body size was adjudged by measurements of weight, height, waist,
      hip and mid upper arm circumferences, and the BMI and waist : hip ratio were
      determined. Of the subjects, 99.2 % had a gynoid pattern of fat distribution.
      Concerns about excess weight were prevalent among the adolescent girls, even
      among those who were normal-weight and underweight. The level of satisfaction
      with body size decreased with increase in weight. Dieting behaviour was reported
      in a higher number of obese (76.6 %) compared with normal-weight (38 %) and
      underweight (14 %) girls. Of the obese girls, 43.3 % were found to be at a
      significantly (P=0.00109) greater risk of developing anorexia in the future.
      Characteristic dietary features of adolescence, such as missing meals, snacking
      and eating out, were observed. While the diets of most of the subjects were
      adequate in Ca, thiamin, riboflavin and vitamin C, they were found to be
      deficient in energy, protein, Fe, niacin, vitamin A and fibre. Thus, it is
      important to recognize that weight concerns and dissatisfaction with body size
      may pose a threat to a healthy nutritional state, and may develop into precursors
      of a later eating disturbance.

PMID- 11591243
TI  - Grain v. cereal: an impediment to public understanding of food and a study in
      language.

PMID- 11591244
TI  - BFS response to the human fertilisation and embryology authority working group on
      new developments in reproductive technology: in vitro maturation of oocytes.

PMID- 11591245
TI  - Practical problems in clinical embryology.

PMID- 11591248
TI  - Fertility 2000: session reports. Embryology 2.

PMID- 11591246
TI  - Fertility 2000: session reports. Female reproductive tract.

PMID- 11591249
TI  - Fertility 2000: session reports. Assisted conception.

PMID- 11591250
TI  - Allocating fertility services by medical need.
AB  - Infertility services often receive little or no public funding because they are
      perceived not to meet a medical need. This article argues that it is plausible to
      think of fertility treatment as a medical need. Medical needs deserve serious
      consideration in resource allocation. Such needs arise when there is a disruption
      of normal species function (disease), which results in a limitation of fair
      equality of opportunity. Fair equality of opportunity is important because it is
      required for a person's ability to live a good life. Infertility can result in a
      medical need because it can be a disruption of normal species function and can
      result in diminished opportunity, which it is highly relevant to the conception
      of a good life of many people. Infertility services deserve serious consideration
      in resource allocation.

PMID- 11591251
TI  - The role of infertility nurses in ovulation induction programmes.
AB  - The role of the infertility nurse is continually expanding and changing to meet
      the demands of couples undergoing assisted reproduction. This article examines
      the responsibilities infertility nurses have in ovulation induction programmes in
      fertility clinics today. A simple questionnaire was sent to all fertility units
      listed in The Patients' Guide to DI and IVF Clinics. There was a response rate of
      71%. Specialist infertility units had a higher number of nurses available to
      carry out various tasks within the fertility programme compared with other types
      of staff. Members of the nursing staff were involved in initial consultation,
      transvaginal ultrasound scanning, intrauterine inseminations, administration of
      medication, sperm preparation and pregnancy tests. Infertility nurses played a
      major role in ovulation induction programmes. In 39% of units, nurses performed
      intrauterine inseminations alone, in 23% of units they made decisions as to the
      requirement for human chorionic gonadotrophin administration, and in over 77% of
      units transvaginal scans were done by nurses. This role could be even broader,
      assuming adequate training is provided and undertaken. The extended role of
      infertility nurse practitioners allows more continuity of care and better
      understanding of patients' needs and results in the involvement of fewer people
      in the overall care.

PMID- 11591252
TI  - Nursing the clinic and managing emotions in a fertility unit: findings from an
      ethnographic study.
AB  - This paper presents the findings from an ethnographic study of a fertility unit.
      Data were collected using participant observation and semi-structured interviews
      over a period of 2 years. Fifteen patients and 23 members of staff were
      interviewed. Data analysis was completed using a modified thematic analysis. The
      findings indicated that the emotions evoked by infertility and medical treatments
      were powerful and frightening. Patients managed their emotions privately although
      they were conscious of an emotional awareness by nurses, which they described as
      'caring'. Nurses were associated strongly with caring and their role was
      primarily to manage emotions; however, to do this, nurses used non-caring
      (emotional distance) rather than caring. Nurses were responsible for managing
      emotions in the public spaces of the clinics and moved between emotional distance
      and awareness according to the needs of the clinic. In this article, it is argued
      that non-caring was a defence against anxiety about coping with painful feelings
      and that the nursing role was to 'nurse the clinic and the doctor' rather than
      the patient.

PMID- 11591253
TI  - Clinical application of preimplantation genetic diagnosis.
AB  - Preimplantation genetic diagnosis (PGD) is an early alternative to prenatal
      diagnosis that is suitable for a small group of patients who are at substantial
      risk of conceiving a pregnancy affected by a known genetic defect. Four centres
      are licensed to perform PGD in the UK. This article reviews the clinical
      experience of PGD at the Guy's and St Thomas' Centre for Preimplantation Genetic
      Diagnosis, now the busiest unit for PGD in the UK, and compares it with
      information from other centres in Europe. The results from the first 40 cycles of
      treatment and the 12 pregnancies arising from those cycles are detailed. It is
      our belief that PGD should be seen as an extension of a clinical genetic service,
      rather than an arm of assisted conception. Making the distinction between
      treatment for infertility and prevention of genetic defect as part of genetic
      service provision may improve access to health service funding for patients
      deserving of PGD.

PMID- 11591254
TI  - The changing nature of elective laparoscopic surgery: a review over a 7 year
      period in a reproductive surgery unit.
AB  - There was a significant increase in the number of laparoscopic procedures
      performed in the Reproductive and Surgery Unit at the Jessop Hospital for Women
      over the 7 year period from 1991 to 1997. The three most common procedures were
      adhesiolysis/salpingo-ovariolysis, treatment of endometriosis and ovarian
      drilling, which together constituted over 80% of all cases. The duration of
      surgery and the complexity of the cases gradually increased with time. The
      determinants of patients staying overnight after laparoscopic surgery in
      decreasing order of importance were: (i) whether they had undergone surgery in
      the morning or in the afternoon; (ii) the operating time; and (iii) the number of
      entry ports used. Most (75%) of the laparoscopic procedures were performed or
      supervised directly by a consultant. In this study period the major complication
      rate was 0.7%.

PMID- 11591255
TI  - Influence of body mass index and self-administration of hCG on the outcome of IVF
      cycles: a prospective cohort study.
AB  - Final maturation of the oocyte in in vitro fertilization (IVF) cycles is achieved
      through the administration of a timed injection of human chorionic gonadotrophin
      (hCG). The success of mature oocyte retrieval is dependent on serum
      concentrations of the hormone reaching values capable of initiating meiosis and
      triggering the release of the cumulus-oocyte complex into the follicular fluid.
      The objective of this prospective cohort study was to examine the effect of
      adiposity, as measured by body mass index (BMI), on serum concentrations of hCG
      and gonadotrophins and to relate this to IVF outcome. A comparison was also made
      between professionally and non-professionally administered hCG to assess any
      possible effect on cycle parameters. A total of 50 patients with a high BMI (> or
      = 26 kg m(-2)) who underwent IVF treatment at the Assisted Conception Unit, St
      James's University Hospital, Leeds, was recruited prospectively into the study.
      They were matched with 50 patients with a normal BMI (18-25 kg m(-2)) who acted
      as a control group. The two groups were matched for age (mean of 32 years and
      range of 22-42 years) and cause of infertility. Serum gonadotrophins, oestradiol
      and hCG concentrations, measured at the time of oocyte retrieval, and the
      clinical outcome of the two groups were compared. Patients with a high BMI had a
      significantly lower mean serum hCG concentration compared with controls (63.9
      versus 99.6 iu l(-1), P < 0.0003). They also required a higher dosage of
      gonadotrophin (3660 versus 3007 iu) to achieve follicular maturation than the
      controls. Similarly, the high BMI group of patients had higher serum
      concentrations of follicle-stimulating hormone (FSH) (12.3 versus 11.2 iu l(-1))
      and lower oestradiol (3499 versus 3506 pmol l(-1)) compared with controls.
      Patients with a high BMI had significantly fewer oocytes aspirated, resulting in
      a significant decrease in the oocyte:follicle ratio compared with controls (33.9
      versus 41.7, P < 0.05). The fertilization rate (46.2 versus 61.3%, P < 0.05) and
      clinical pregnancy rate per cycle (26.6 versus 37.1%, P < 0.05) were also lower
      in the patients with high BMI compared with those with normal BMI. The
      administration of hCG by the patient or her partner did not have a significant
      effect on clinical outcome. The mean serum hCG at the time of oocyte recovery was
      equivalent in both groups (87.1 versus 89.7 iu l(-1)). Furthermore, the
      oocyte:follicle ratio (0.73 versus 0.72), fertilization rate (46.2 versus 54.2%)
      and clinical pregnancy rate (38.9 versus 36.5%) were similar. These findings
      indicate that high BMI is detrimental to the success of IVF treatment and has an
      important influence on the distribution and metabolism of hCG. The results also
      indicate that non-professional administration of hCG does not compromise cycle
      outcome.

PMID- 11591256
TI  - The effects of female age on fecundity and pregnancy outcome.
AB  - In industrialized countries worldwide, women are delaying childbearing for a
      variety of reasons, including pursuit of career, greater financial independence,
      improved and more accessible contraception and longer life expectancy. In terms
      of fertility and maternity, those aged > or = 35 years are considered to be of
      advanced maternal age and there are usually marked reductions in both the
      fecundity rate for spontaneous conceptions and the success rates with assisted
      conception. These decreases are thought to be due mainly to oocyte ageing, and
      the established success of oocyte donation from younger individuals to older
      recipients supports this contention. For those who achieve a pregnancy at an
      advanced maternal age there is a greater likelihood of aneuploidy (assuming
      conception with the woman's own oocytes), hypertensive and other medical
      disorders, birth by Caesarean section and maternal mortality. However, most of
      the complications associated with advanced maternal age are caused by age-related
      confounding variables, and older premenopausal women in good health should not
      require special attention. The data on perinatal mortality rates are encouraging
      and in the absence of congenital abnormalities perinatal mortality is probably
      not much increased, if at all, in older mothers. Pregnancy is now possible for
      postmenopausal women with the application of oocyte donation, but these
      individuals have a significantly higher likelihood of cardiovascular ageing and
      should be considered at increased risk of vascular complications during
      pregnancy.

PMID- 11591257
TI  - Infertility.

PMID- 11591258
TI  - Conference consensus statement: ethical and research dilemmas for fertility
      preservation in children treated for cancer.

PMID- 11591259
TI  - Reactive oxygen species and sperm.

PMID- 11591260
TI  - Royal college of nursing fertility nurses group regional workshop.

PMID- 11591261
TI  - Infertility: past, present and future -- a personal view.

PMID- 11591262
TI  - Efficacy and safety of long-acting GnRH agonists in in vitro fertilization and
      embryo transfer.
AB  - The introduction of gonadotrophin-releasing hormone (GnRH) agonists combined with
      gonadotrophins is considered to be one of the most significant events in the
      development of in vitro fertilization and embryo transfer (IVF-ET) programmes.
      This article reviews the use of GnRH agonists in IVF-ET programmes and the
      efficacy and safety of long-acting GnRH agonists. The use of agonists results in
      higher clinical pregnancy rates, more supernumerary embryos for cryopreservation
      and allows convenient programming of oocyte recovery. There are different types
      of agonist and ovarian stimulation protocol available for clinical use. Recent
      meta-analysis of the Cochrane database has demonstrated the superiority of the
      long protocols over the short and ultra-short protocols for GnRH agonist use in
      IVF and GIFT. The depot injection offers increased clinical and patient
      compliance and improves efficacy of pituitary downregulation. However, compared
      with short-acting agonists, the depot preparations are associated with a longer
      period of stimulation and higher doses of gonadotrophins. To date, there is no
      evidence of an increased risk of pregnancy wastages or teratogenicity in human
      pregnancies exposed to long-acting agonists.

PMID- 11591263
TI  - Sedation and analgesia for transvaginal oocyte retrieval: an audit resulting in a
      change of clinical practice.
AB  - The aim was to audit the standard of care at oocyte retrieval with respect to the
      analgesia used. Before June 1999, a combination of intramuscular pethidine and
      prochlorperazine was given as a single dose. Many women found this to be
      unsatisfactory and requested general anaesthesia for subsequent oocyte
      retrievals. An intravenous sedation and analgesia regimen was introduced using a
      combination of midazolam and fentanyl. The introduction of this regimen was
      audited and compared with the established regimen. This study describes the
      experience with this technique, its patient acceptability, safety and cost
      implications.

PMID- 11591264
TI  - A physiological replacement for polyvinylpyrrolidone (PVP) in assisted
      reproductive technology.
AB  - The technique of intracytoplasmic sperm injection (ICSI) requires mechanical
      immobilization of the sperm that are to be injected; damage thus caused to the
      sperm membrane is considered to be necessary to activate the sperm for
      fertilization. Mechanical immobilization and the injection procedure are
      facilitated by introducing the sperm into a viscous medium that will hinder
      motility: a solution of polyvinylpyrrolidone (PVP) has been used successfully for
      this purpose. PVP is an artificial polymer, which has been regarded as chemically
      inert, although adverse effects have been reported as a result of its use both in
      vivo and in vitro. Therefore, the use of hyaluronate, the natural component of
      the extracellular matrix of the cumulus-oocyte complex, was investigated as a
      replacement for PVP during ICSI. A solution of hyaluronate was found to be as
      effective as PVP in facilitating the injection procedure, its effect on sperm
      motility was readily reversible, and its use did not affect the outcome of the
      treatment cycles in terms of fertilization, pregnancy and live birth rates. Every
      attempt should be made to eliminate artificial factors in assisted reproductive
      procedures. Hyaluronate, a natural and readily degradable glycosaminoglycan can
      be used as a substitute for the artificial PVP polymer without jeopardising the
      outcome of the treatment cycle.

PMID- 11591265
TI  - Blastocyst transfer for patients with multiple assisted reproduction treatment
      failures: preliminary experience.
AB  - This preliminary study reports the results obtained from a patient group in which
      blastocyst culture and transfer were performed, and discusses the advantages and
      disadvantages of introducing blastocyst transfer in a clinic. Twenty-six patients
      who had failed to achieve a pregnancy in previous in vitro fertilization (IVF)
      and intracytoplasmic sperm injection (ICSI) treatments were offered the choice of
      a fresh cycle with culture to the blastocyst stage. Of the 26 patients who
      elected to attempt blastocyst culture, 11 opted to have transfer on day 2 or day
      3 due to low numbers of embryos. Of the 15 patients who proceeded to blastocyst
      culture, 46.2% of the embryos cultured reached the blastocyst stage or later and
      eight of the patients achieved a clinical pregnancy. More oocytes were collected
      in this patient group, hence the chances of obtaining blastocysts were higher.
      Offering blastocyst culture to patients with a reasonable chance of success who
      have had previous multiple assisted reproduction failures is an acceptable way of
      introducing blastocyst culture into practice.

PMID- 11591266
TI  - Blastocyst culture: myth or magic?
AB  - The development of sequential serum-free culture medium has led to a reported
      increase in implantation rate after transfer of embryos on days 5-6
      (approximately 40%) compared with those achieved after transfer on days 2-3
      (approximately 20%). However, there are numerous uncertainties surrounding
      extended culture that need to be considered. This article examines some of the
      problems and questions considered in relation to the following areas: the
      developmental capacity of the embryo in vitro; the uterine environment after
      embryo transfer; the clinical indications surrounding blastocyst transfer
      including a reduction in multiple pregnancy rate and relevance in preimplantation
      genetic diagnosis (PGD); and the introduction of blastocyst culture into the
      embryology laboratory.

PMID- 11591267
TI  - Adolescent sexual and reproductive health: the challenge for society.
AB  - Within almost all countries of the world there is a growing concern about the
      sexual and reproductive health of adolescents. This concern has resulted from
      either a real or a perceived increase in adolescent sexual activity, coupled with
      high rates of unplanned pregnancies, early childbearing and the transmission of
      sexually transmitted infections, including HIV. Although many adults have
      difficulties in accepting young people as sexual beings, there is now a growing
      consensus that young people need more information and services to help them
      ensure their sexual and reproductive health. Many of the programmes designed to
      make sexual and reproductive health information and services available to young
      people have used 'top down' approaches, based on adult-led risk and lifestyle
      orientation. In such programmes, young people are often looked upon negatively,
      in terms of their problems, rather than positively, in terms of their potential
      and capabilities. This article argues that a focus on the negative aspects of
      adolescent sexual and reproductive health means that young people are seen as
      collections of discrete problems. Furthermore, such approaches tend to view all
      young people as one homogeneous group when in reality adolescents are an
      enormously diverse group, not only in terms of age and gender, but also in terms
      of ability and beliefs. Such approaches therefore fail to address the
      vulnerabilities of particular young people and fail to contextualize sexual
      health within a wider framework of young people's lives. A challenge for the next
      century is to move away from focusing on risks, towards embracing needs and
      rights, and to involve young people in identifying issues and developing
      solutions.

PMID- 11591268
TI  - Semen collection from young cancer patients.

PMID- 11591269
TI  - So you think it won't affect you? Assisted conception, discrimination and the
      Human Rights Act.

PMID- 11591270
TI  - The extended role of the nurse--opportunity or threat?
AB  - Nursing practice is undergoing changes that are both exciting and controversial.
      The UKCC Scope of Professional Practice has encouraged nurses to re-evaluate
      their practice and, as a result, nurses from various fields have expanded their
      roles to meet the changing needs of patients and the profession. Published
      evidence shows that nurses can be as effective as doctors within these expanded
      roles, but that there is a danger that gender issues will cloud the debate
      because of the assumption that all nurses are female and all doctors are male.
      This problem is especially evident when female nurses perform an extended role
      involving male patients, although female doctors are in a similar position and
      work with the same patients without undue comment. The roles of doctors and
      nurses should complement each other, and all practitioners should work for the
      benefit of patients in their care, rather than defending traditional roles and
      hierarchy. There is confusion surrounding accountability of nurses who work in an
      extended role between the medical and the nursing profession, and both the Royal
      College of Nursing and the British Medical Association need to clarify the
      situation. This article looks at the arguments for and against the extended role
      of the nurse specialist and discusses current opinions within the nursing and
      medical fields. The article also describes how nurses at Midland Fertility
      Services have successfully extended their role to encompass ultra-sound-guided
      oocyte retrieval and surgical sperm recovery.

PMID- 11591271
TI  - Clomiphene citrate in the twenty-first century.
AB  - Clomiphene citrate is the drug most commonly prescribed for ovulation induction.
      It is the first choice medication in normogonadotrophic oligo/amenorrhoeic
      infertility (WHO group 2), essentially associated with polycystic ovaries.
      Anovulatory women who are responsive to clomiphene citrate should be treated for
      at least six cycles and the treatment should probably be limited to a maximum of
      12 cycles. It is necessary to monitor at least the first cycle with
      ultrasonography because of the risk of multiple pregnancy and the variable
      response of patients to different doses of clomiphene. In addition, the risk of
      ovarian hyperstimulation syndrome should not be underestimated. More triplets and
      higher order pregnancies result from ovulation induction than from in vitro
      fertilization, and multiple pregnancy has many risks for both mother and babies.
      The role of empirical clomiphene in the treatment of unexplained infertility is
      debatable and the present data are inconclusive. Obesity, hyperandrogenaemia and
      insulin resistance are important factors in clomiphene-resistant patients.
      Failure to ovulate in response to clomiphene has been approached by either
      medical or surgical treatment. An effective alternative medical treatment is
      gonadotrophin injections. Treatment with metformin and the new generation of
      insulin-sensitizing drugs is under evaluation. The most widely used surgical
      treatment today is laparoscopic ovarian drilling, which appears to be as
      effective as gonadotrophin therapy.

PMID- 11591272
TI  - Cryopreservation of human oocytes.
AB  - Cryopreservation is a well established technique by which preimplantation stage
      embryos can be stored for later use. However, it would be preferable to
      cryopreserve unfertilized oocytes to overcome the problems related to the ethical
      and legal status of the embryo. This procedure has been successful in mice, but
      attempts to extend this approach to other species have been less successful. In
      human in vitro fertilization (IVF) in particular, very few live births have been
      reported after the cryopreservation of oocytes. The reason for this lack of
      success is unclear. The widespread contention that compromised oocyte viability
      originates principally from damage to the meiotic spindle induced by
      cryopreservation conditions is unproven. The treatment of large groups of women
      has shown that pregnancies derived from stored oocytes can be achieved in a
      reproducible fashion, although success rates are still lower than those derived
      from frozen embryos. To date, human oocytes have been stored largely by applying
      methods originally designed for cleaving embryos. Therefore, it is reasonable to
      envisage that appropriate modification of current freezing techniques will
      increase survival rates and make oocyte storage an important option in IVF
      treatment.

PMID- 11591273
TI  - Cryopreservation of human sperm.
AB  - Freezing of human sperm is considered a routine procedure in assisted
      reproductive technology (ART) laboratories. This article considers various
      aspects of cryopreservation of human sperm. Human sperm show a specific
      cryophysical behaviour and different sperm freezing protocols have been developed
      to avoid damage to the sperm cells. The damage can range from impaired motility
      and reduced viability to damage to the cellular organelles and effects at the
      molecular level, resulting in an impaired fertilizing potential. As testicular
      sperm are immature and only a small number can be retrieved, special techniques
      are required for successful freezing and thawing of these samples. Banking of
      human sperm has to be performed in a safe and controlled way and different
      guidelines are necessary to ensure that this is achieved.

PMID- 11591274
TI  - Donor insemination: a question of rights.

PMID- 11591275
TI  - Successful pregnancy outcomes after preimplantation genetic diagnosis (PGD) for
      carriers of chromosome translocations.
AB  - Reciprocal translocations are found in about 1 in 500 people, whereas
      Robertsonian translocations occur with a prevalence of 1 in 1000. Balanced
      carriers of these rearrangements, although phenotypically normal, may present
      with infertility, recurrent miscarriage, or offspring with an abnormal phenotype
      after segregation of the translocation at meiosis. Once the translocation has
      been identified, prenatal diagnosis can be offered, followed by termination of
      pregnancies with chromosome imbalance. Couples who have suffered repeated
      miscarriage or those who have undergone termination of pregnancy as a result of
      the translocation carrier status of one partner are looking increasingly to
      preimplantation genetic diagnosis (PGD) as a way of achieving a normal pregnancy.
      Similarly, infertile couples in which one partner is a translocation carrier may
      request PGD to ensure transfer of normal embryos after in vitro fertilization.
      Translocation PGD has been applied successfully in several centres worldwide and
      should now be considered as a realistic treatment option for translocation
      carriers who do not wish to trust to luck for a successful natural outcome.

PMID- 11591276
TI  - Regulation of the transition from research to clinical practice in human assisted
      conception.
AB  - This review discusses the place of regulation in the transition from research to
      clinical practice in human assisted conception, with particular emphasis on the
      United Kingdom and the role of the Human Fertilisation and Embryology Authority
      (HFEA). A contrast is drawn between advances in other areas of medical practice,
      in which the evidence base is considerable, and in assisted conception, in which
      it is often weak. This comparison leads to the central issue: how to balance the
      needs of patients with the need to ensure safety and efficacy in the introduction
      of new techniques. Comfort is derived from biological considerations that
      indicate that early human embryos are remarkably resilient and adaptable to
      challenges to their physiology. Regulatory practice in other countries is
      considered briefly. The review concludes that there are no easy rules or answers
      in managing the transition from research into the clinic, but that bodies such as
      the HFEA have a responsibility to: (i) encourage research to widen the evidence
      base and (ii) err on the side of caution when faced with decisions on licensing
      new techniques.

PMID- 11591277
TI  - [Anesthesia outside the operating theater: relegated to the high seas or luxury
      liners?].

PMID- 11591278
TI  - [Preoperative testing routines for healthy, asymptomatic patients in the Canary
      Islands (Spain)].
AB  - OBJECTIVES: To analyze patterns of routine testing before elective/scheduled
      surgery in healthy/asymptomatic patients classified as ASA I or II according to
      the American Society of Anesthesiologists. MATERIAL AND METHOD: A questionnaire
      on the organization of preoperative testing was completed by anesthesiologists at
      five public hospitals in the Canary Islands. The questionnaire emphasized the
      most commonly ordered screening procedures, such as chest X-rays,
      electrocardiograms, laboratory tests and spirometry. RESULTS: Red cell counts
      were most frequently requested (for 86% of the patients), followed by platelet
      counts (80%) and blood chemistry (75%) and coagulation studies (72%). Least
      requested were urine tests and spirometry. The frequencies of electrocardiogram
      and chest X-ray requests fell between the two extremes, with patient age and the
      presence of certain indications seeming to affect whether those tests would be
      ordered or not. The need for such screening was perceived to increase for
      patients over 40 years of age. The ordering of preoperative tests varied from
      hospital to hospital and among anesthesiologists at a single site in spite of
      established protocols. CONCLUSIONS: Hospitals and individual anesthesiologists
      differ considerably in how they request preoperative tests. The variations can
      not be explained solely by differing patient needs given that respondents were
      contemplating only healthy/asymptomatic individuals undergoing relatively simple
      procedures.

PMID- 11591279
TI  - [Use of the electroencephalographic spectral edge frequency 90 to monitor
      sedation of chronically ill patients].
AB  - INTRODUCTION: The depth of sedation required for patients in critical care units
      varies over time and should be subject to control. The clinical assessment scales
      used at present are inadequate, and several electroencephalographic variables
      have been investigated in recent years with the aim of quantifying depth of
      sedation. One such variable is the spectral edge frequency 90 (SEF90).
      OBJECTIVES: To establish the correlation between SEF90 and the Ramsay score as
      indicators of depth of sedation. To estimate the ability of SEF90 to predict
      sedation and a patient's hemodynamic response during aspiration of secretions
      through the orotracheal tube. PATIENTS AND METHODS: Patients in a surgical
      intensive care unit. The ability of SEF90 to predict a certain Ramsay score was
      assessed by logistic regression. We also calculated the predictive probability
      (Pk) of SEF90 for the appearance of hemodynamic change and of movement in the
      event of endotracheal aspiration. RESULTS: When SEF90 was < 16 Hz, the
      probability of a Ramsay score >= 4 was >= 90% (Pk = 0.91). Neither SEF90 nor the
      Ramsay score predicted hemodynamic response to orotracheal aspiration.
      CONCLUSIONS: SEF90 distinguishes superficial from deep sedation but does not
      differentiate further degrees of depth or the likelihood of hemodynamic
      instability or movement in response to aspiration.

PMID- 11591280
TI  - [Changes in the bispectral index and the spectral edge frequency 90 during
      different phases of anesthesia with sevoflurane].
AB  - INTRODUCTION: Electroencephalographic monitoring is one of the techniques used to
      measure hypnosis during anesthesia. Efforts to find a means to apply this
      monitoring function are justified by cases of intraoperative awakening and are in
      the interest of guaranteeing patient welfare and controlling anesthesia.
      OBJECTIVES: To determine the changes in two electroencephalographic parameters,
      the bispectral index (BIS) and the spectral edge frequency 90 (SEF90), during the
      different phases of anesthesia. Patients and method. Forty-eight patients
      undergoing abdominal surgery were studied prospectively. Anesthesia was induced
      by propofol, fentanyl or sevoflurane. Anesthesia was maintained with sevoflurane
      and O2/N2O at a concentration of 70% to maintain BIS between 40 and 60. Variables
      monitored were heart rate, blood pressure, arterial oxygen saturation (with a
      pulse oximeter), expired CO2 partial pressure, inspired and expired sevoflurane
      partial pressure, esophageal temperature, SEF90 (defined as the frequency below
      which 90% of the power in the electroencephalogram resides) and BIS. All
      variables were recorded during three phases: induction, maintenance and recovery
      from anesthesia. We then performed an analysis of variance, with p < 0.05
      considered significant. RESULTS: During induction mean BIS decreased from 95.6 to
      34.7 after intubation, while SEF90 fell from 20.5 Hz to 11.9 Hz. During
      maintenance BIS, SEF90 and expired sevoflurane partial pressure remained
      constant. During recovery mean BIS increased from 59.2 to 92.3 upon extubation,
      and SEF90 went from 15.1 to 22.2 Hz; although heart rate increased, blood
      pressure did not. The mean electroencephalographic values recorded when movement
      occurred were 77 for BIS (range 58-96) and 18 for SEF90 (range 13-18).
      CONCLUSION: Electroencephalographic monitoring is useful for distinguishing
      between states of consciousness and unconsciousness during anesthesia, and is
      valid for the phases of induction and recovery. BIS values over 58 and SEF90
      values over 13 may indicate inadequate hypnosis.

PMID- 11591281
TI  - [Neurotoxicity of intrathecal lidocaine].
AB  - Lidocaine is a local anesthetic belonging to the amide group and has been
      administered intrathecally for over 40 years. Although no serious complications
      had been attributed to lidocaine before the 1990s, subarachnoid administration is
      now the subject of controversy following its implication in numerous cases of
      neurological complication. The clinical pictures described in the literature are
      cauda equina syndrome, which is mainly associated with continuous subarachnoid
      anesthesia through microcatheters, and transitory neurological symptoms, also
      termed radicular irritation syndrome and associated with single injections. The
      literature reveals a clearly higher incidence of transitory neurological symptoms
      with lidocaine than with other local anesthetics. Although the underlying
      mechanism remains unclear, the main hypotheses being the neurotoxicity of
      lidocaine itself or the malpositioning of the paravertebral musculature due to
      extreme relaxation. The various factors that can lead to neuropathy have been
      widely described in the many articles reporting complications. Arthroscopy and
      lithotomy positions are significantly related to the appearance of symptoms, as
      are early ambulation or the use of small-gauge needles or pencil-point needles.
      Further clinical studies should be undertaken. No consensus on subarachnoid
      administration of lidocaine has emerged, yet no alternative has been demonstrated
      to be safe and to offer similar pharmacological features (short latency, short
      duration of action and good muscle relaxation). Prilocaine, mepivacaine,
      articaine and bupivacaine at low doses have been suggested as alternatives.

PMID- 11591282
TI  - [Cauda equina syndrome after intradural anesthesia with bupivacaine].
AB  - A 70-year-old man developed pain and functional weakness in the lower limbs with
      dysesthesia and urinary retention after subarachnoid anesthesia with 0.5%
      hyperbaric bupivacaine. Neurological and electrophysiological tests and follow
      up, as well as diagnostic images (CAT and MR), ruled out spinal cord lesions. The
      diagnosis was cauda equina syndrome. Cauda equina syndrome is a neurological
      complication of subarachnoid anesthesia. Associated with use of microcatheters
      for continuous subarachnoid anesthesia and 5% hyperbaric lidocaine, cauda equina
      syndrome is rare after a single injection of bupivacaine. Although the
      pathogenesis of cauda equina syndrome is poorly understood, there is agreement on
      the neurotoxicity of local anesthetics, particularly of 5% hyperbaric lidocaine.

PMID- 11591283
TI  - [Improved oxygenation with nitric oxide treatment for hepatopulmonary syndrome
      after a liver transplant].
AB  - A 37-year-old man with cirrhosis of the liver hospitalized for orthotopic liver
      transplant (OLT) was found to have hepatopulmonary syndrome (HPS) during routine
      presurgical assessment. No problems with oxygenation developed during surgery. In
      the early recovery period, however, hypoxemia was observed to be uncorrected in
      spite of gradual normalization of liver function tests. OLT sometimes corrects
      HPS and, therefore, hypoxemia. However, significant decreases in oxygenation
      during recovery have been reported to affect patient morbidity and mortality. We
      therefore started low-dose nitric oxide (NO) inhalation once other possible
      causes of hypoxemia had been ruled out. Oxygenation improved, allowing tubes to
      be removed. Seven months after OLT, home oxygen therapy was still required to
      treat basal hypoxemia. HPS persisted, as confirmed by echocardiogram. Inhaled NO
      contributed to maintenance of adequate oxygenation during the early postoperative
      period, as essential for long-term survival in patients with HPS who undergo OLT.

PMID- 11591284
TI  - [Monitoring of the EEG bispectral index could be a good indicator of the
      neurological evolution of patients in coma of metabolic origin].

PMID- 11591285
TI  - [Incidence of transient neurologic symptoms after subarachnoid anesthesia with
      mepivacaine in ambulatory major surgery].

PMID- 11591286
TI  - [Anesthesia in Prader-Willi syndrome for major surgery for kyphoscoliosis].

PMID- 11591287
TI  - [Non-cardiogenic acute edema of the lung after recurrent air venous embolism].

PMID- 11591288
TI  - [Use of esmolol in patient with portal hypertension].

PMID- 11591289
TI  - [Models of anesthesia practice in Europe].

PMID- 11591292
TI  - [Did we need to show, also in Spain, that cholesterolemia and tobacco are
      cardiovascular risk factors?].

PMID- 11591293
TI  - [Cholesterol and tobacco: classics that withstand the passing of time].

PMID- 11591294
TI  - [Risk factors and coronary morbimortality in a Mediterranean industrial cohort
      over 28 years of follow-up. The Manresa Study].
AB  - OBJECTIVE: To study the incidence and mortality of coronary heart disease (CHD)
      and all-cause mortality in a cohort of men followed during 28 years, and their
      association with serum cholesterol, systolic blood pressure, glycemia, cigarette
      smoking and body mass index measured at baseline. RESEARCH DESIGN AND METHODS: A
      cohort of 1,059 men aged 30 to 59 years and free of cardiovascular diseases at
      baseline in 1968, was examined every five years until 1988. The last examination
      was performed in 1996. Information was collected in 96.4% of the participants.
      RESULTS: Incidence and mortality rates from CHD and from all-causes of death per
      105 person-years of observation were 499.80, 235.80 and 925.33, respectively. At
      the end of follow-up, high levels of serum cholesterol and smoking were
      independently associated with the incidence and mortality from CHD adjusted for
      age, blood pressure, glycemia and BMI. Serum cholesterol, hyperglycemia and
      smoking were independently associated with all-cause mortality. CONCLUSIONS: In
      this industrial cohort of men, with a relatively low incidence of CHD, smoking
      and serum cholesterol at baseline were independently associated with the
      incidence of CHD over 28 years of observation.

PMID- 11591295
TI  - [Thrombogenic and endothelial damage markers in patients with ischemic systolic
      impairment].
AB  - INTRODUCTION: Anticoagulation is rarely indicated in patients with left
      ventricular dysfunction who show an increased risk for thromboembolism. In
      theory, the three arms of the Virchow' triad may be present: abnormal blood flow,
      endothelial damage and prothrombotic markers. The aim of this study was to
      identify the last two arms. PATIENTS AND METHOD: We studied 82 consecutive
      patients with demonstrated ischaemic heart disease and sinus rhythm, and compared
      them with a control group comprised of 32 healthy subjects matched for age and
      sex. None or the patients had had an acute coronary event or hemodynamic
      decompensation within the 3 months prior to inclusion in the study. The plasma
      concentration or von Willebrand factor and fibrin d-dimer and fibrinogen were
      determined as endothelial damage and prothrombotic markers, respectively. A
      fractional shortening less than 29% by echography was defined as ventricular
      systolic dysfunction. RESULTS: The patients showed significantly higher levels of
      von Willebrand factor with respect to the control group (109.2 31.9 vs 85.5
      32.6%, p < 0.01), with no differences in fibrinogen and fibrin d-dimer values.
      Twenty-six patients fulfilled criteria of left ventricular systolic dysfunction.
      Patients with left ventricular dysfunction showed higher fibrinogen (386 118 vs
      322 102 mg/dl, p = 0.03) and fibrin d-dimer (0.36 0.22 vs 0.26 0.10 g/ml; p =
      0.04) levels, with no differences in von Willebrand factor levels. CONCLUSIONS:
      After acute coronary events, patients with ischaemic heart disease show markers
      of endothelial damage. However, patients with left ventricular dysfunction show a
      hypercoagulable state.

PMID- 11591296
TI  - [The influence of angina the week before a first myocardial infarction on short
      and medium-term prognosis].
AB  - INTRODUCTION AND OBJECTIVES: The implications of early angina on the prognosis of
      myocardial infarction are controversial. The aim of this study was to assess the
      effect of angina one week before the first myocardial infarction on short and
      medium-term prognosis. PATIENTS AND METHOD: A total of 290 consecutive patients
      (107 with previous angina and 183 without it) with the first myocardial
      infarction were studied to determine the effect of preceding angina on short and
      medium-term prognosis. Further criteria for inclusion were no previous history of
      angina > 1 week before the first myocardial infarction, and no evidence of prior
      structural cardiopathy. The end points studied were death and congestive heart
      failure in the acute phase of myocardial infarction and during the follow-up.
      RESULTS: Patients with a history of prodromal angina were less likely to
      experience in-hospital death, heart failure or combined end-point (3.7 vs 11.5%;
      4.6 vs 15.8%; 7.5 vs 21.3%) (p = 0.002). There was also a difference between
      groups in the follow-up (4.1 vs 13.2%; p = 0.03). Multivariate analysis confirmed
      that the presence of preinfarction angina was an independent predictor of death
      and heart failure in the acute phase of myocardial infarction as well as in the
      follow-up. CONCLUSIONS: The occurrence of angina one week before the first
      myocardial infarction protects against death and heart failure in the acute phase
      of myocardial infarction as well as in the medium follow-up.

PMID- 11591297
TI  - [Sudden death caused by atheromatous coronary disease in the young].
AB  - INTRODUCTION AND OBJECTIVES: Atheromatous coronary disease (ACD) is the most
      frequent cause of sudden death (SD) in adults. Few studies have focused in SD due
      to ACD in those patients under 35 years old. The aim of this study is to analyze
      the incidence, and clinical and pathological characteristics of ACD as a cause of
      death in young people. MATERIAL AND METHODS: We reviewed all SD cases in people
      from 1-35 years old which occurred in Bizkaia and in which there was a legal
      medical autopsy from 1991 to 1998. A complete autopsy was performed in each case.
      SD due to ACD were analyzed, including pathological antecedents. RESULTS: 19 out
      of 107 SD (18%) occurred by ACD. All of them were males from 27 to 35 years of
      age. According to the male population from 30 to 35 years, the incidence was
      3.7/100,000/year. In two patients ACD was diagnosed before death. Coronary risk
      factors were obtained in 10 cases and prodromal symptoms were described in 5
      (chest pain in 4). In 79% death occurred during routine activity. None of the 19
      patients arrived alive to hospital. In 6 cases multiple coronary disease was
      observed; coronary thrombosis in 8; recent acute ischemic myocardial necrosis in
      4 and old ischemic damage in 7. 18 cases showed cardiac hypertrophy. CONCLUSIONS:
      ACD is an important cause of SD in young males, frequently being the first
      manifestation of the disease. As identification of groups at risk is so difficult
      and death occurs so quickly, primary prevention of ACD, rapid intervention of
      emergency services and educational programs in cardiopulmonar resuscitation for
      normal population are fundamental in reducing the mortality.

PMID- 11591298
TI  - [The non Q wave myocardial infarction in conventional valvular surgery. Diagnosis
      with cardiac troponin I].
AB  - INTRODUCTION: Morbidity and mortality in elective valve surgery is still
      significant. The main cause of death in these patients is cardiogenic shock, of
      which the most frequent etiology is acute myocardial infarction (AMI) with Q wave
      in the ECG. However, there are patients with cardiogenic shock without Q wave in
      the ECG and with rises in CK-MB enzyme that makes us suspect non-Q wave AMI.
      OBJECTIVE: To analyze the use of the determination of cardiac troponin-I, a more
      specific marker of AMI than CK-MB after cardiac surgery, to detect perioperative
      non-Q wave AMI, and to establish its clinical significance. METHODS: A total of
      147 patients without coronary artery disease scheduled for elective valve surgery
      were included. We used, based in anterior publications, ECG (presence or not of
      new Q wave) and cardiac troponin I to define perioperative AMI. Levels of cardiac
      troponin-I were analysed before surgery and 14 hours after. Non-Q wave AMI was
      diagnosed when troponin I was superior to 38.85 ng/ml and there was not a
      phatologic Q wave in ECG. RESULTS: One hundred twenty-three (83.67%) of patients
      did not have AMI, 9 (6.12%) suffered perioperative AMI with Q wave, and 15
      (10.27%) carried out criteria of non-Q wave perioperative AMI. Morbidity and
      mortality in this last group was similar to that in the group with Q wave AMI.
      Morbidity and mortality were minimum in patients without AMI. CONCLUSIONS: This
      study suggest the possibility of in vivo identification of non-Q wave
      perioperative AMI, an entity with important morbidity and mortality in our
      series, with a simple determination of cardiac troponin I 14 hours after surgery.

PMID- 11591299
TI  - [Diastolic dysfunction in human immunodeficiency virus infection].
AB  - AIMS: We sought to determine the prevalence and characteristics of
      echocardiographic abnormalities (systolic and/or diastolic dysfunction,
      pericardial effusion) in patients with human immunodeficiency virus infection
      (HIV) with no symptoms or previous history of cardiac disease, and compare them
      with a healthy control group. PATIENTS AND METHOD: Transthoracic echocardiography
      was performed in 125 patients (73% male, mean age 33.2 +/- 6.6 years) with HIV
      infection without cardiac involvement and 47 age and sex-matched healthy
      volunteers (78% male, 31.6 +/- 7.3 years). The immunologic situation was
      determined by CD4 lymphocyte counts. RESULTS: Abnormal left ventricular
      relaxation and filling patterns (E/A relation 1.31 +/- 0.35 in HIV group, 1.66 +/
      0.38 in control group, p < 0.001; pressure half-time 57.5 +/- 13 in HIV group,
      50.6 +/- 6.6 in control group, p < 0.001), segmental wall-motion abnormalities
      (15%) and pericardial effusion (7.2%) were found in patients with HIV infection.
      Systolic function (EF 64.8 +/- 8.3) and left ventricular dimension (diastolic
      diameter 4.94 +/- 0.55, systolic diameter 3.17 +/- 0.51) showed normal patterns
      and did not significantly differ from those of the control group. CONCLUSIONS:
      Silent echocardiographic abnormalities in patients with HIV infection are
      frequent suggesting a direct myocardial effect of the virus. The development of
      diastolic dysfunction is directly related to a worse immunologic situation.
      Prospective studies are needed to clarify the clinical prognosis of these
      asymptomatic abnormalities.

PMID- 11591300
TI  - [Percutaneous closure of atrial septal defect with the Amplatz device: initial
      result and mid-term follow-up].
AB  - OBJECTIVES: Percutaneous device occlusion of atrial septal defects (ASD) is,
      although with some limitations, an alternative to surgical closure. The aim of
      this study was to evaluate the efficacy and safety of percutaneous ASD closure
      using the Amplatz device. PATIENTS AND METHODS: From October 1999 to March 2000,
      25 children underwent transcatheter closure of ASD at a mean +/- SD age of 8.7 +/
      3.1 years (range 3-15 years) and a mean weight of 31.8 +/- 16.7 kg (range 11-84
      kg). Device selection was based on the stretched diameter of the ASD using the
      PTA OS balloon. The device was implanted under ultrasonographic and radiological
      guidance. All patients showed signs of volume-overload of the right ventricle.
      The ASD was single (n = 21), with two separate holes (n = 2), or cribiform (n =
      2). RESULTS: The median +/- SD size of the device used was 21.7 +/- 5.4 mm (range
      15-36 mm). In twenty-two patients (88%) the device was successfully implanted. A
      repeat echocardiogram was performed the next day before discharge. Two patients
      underwent surgery after deployment of the device due to mitral valve dysfunction
      (n = 1) or residual leak (n = 1). In a patient with a two-hole ASD, another
      device was percutaneously withdrawn, while still attached to the delivery cable
      due to incomplete occlusion. CONCLUSION: a) Transcatheter occlusion with the
      Amplatzer device is an effective treatment for ostium secundum atrial septal
      defects; b) the low complication rate and the short hospitalization period makes
      this procedure the treatment of choice in these patients, and c) ASD which are
      too large, cribiform or with deficient rims may require a different approach.

PMID- 11591301
TI  - [Current status of intracoronary brachytherapy].
AB  - Intracoronary radiation therapy or intracoronary brachytherapy has been developed
      as an attempt to decrease restenosis after percutaneous coronary interventions.
      Two parallel technologies, one employing radioactive stents, the other catheter
      based radiation (using either beta- or gamma- emitters), have been the subject of
      numerous animal and human studies. In vivo intravascular ultrasound imaging
      studies have played a major role in determining the possible mechanism of action
      of intracoronary radiation therapy and the pathogeny of many of the complications
      related to the use of this technique. This manuscript is aimed at revising the
      potential and limitations of intracoronary brachytherapy, as well as at
      summarizing the results of the currently reported clinical trials.

PMID- 11591302
TI  - [Growth factors for therapeutic angiogenesis in cardiovascular diseases].
AB  - Therapeutic angiogenesis based on the administration of growth factors with
      angiogenic activity allows enhancement of collateral vessels able to palliate
      insufficient tissue perfusion secondary to obstruction of native arteries. At
      present, this type of therapy is addressed to patients that fail to respond to
      conventional treatment (surgical or percutaneous revascularization). The most
      extensively investigated angiogenic growth factors are vascular endothelial
      growth factor (VEGF) and fibroblast growth factor (FGF). These cytokines can be
      administered either as recombinant proteins or as the genes encoding for these
      proteins. Both approaches have pros and cons that are under investigation in
      animal models and in clinical studies. Although clinical trials consist so far of
      small, often non-randomized series, preliminary results are promising. For
      example, administration of VEGF or FGF has been associated to objective evidence
      of increased tissue perfusion in patients with myocardial ischemia, and to a
      significant improvement of pain and ischemia in patients with peripheral arterial
      disease. Contrarily to expected, these interventions have been associated to
      scant adverse side effects, although larger clinical trials will be necessary in
      order to prove the safety and effectiveness of these interventions. Nevertheless,
      it seems clear that it is feasible to induce effective therapeutic angiogenesis
      in selected patients without significant associated toxicity.

PMID- 11591304
TI  - [Allergic reaction to streptokinase].

PMID- 11591305
TI  - [Transient complete atrioventricular block following a nonpenetrating chest
      trauma].
AB  - Cardiac contusion may cause disorders of impulse formation and propagation in the
      specific conduction system. Transient complete atrioventricular block following a
      nonpenetrating chest trauma is a rare complication.We describe the case of a
      patient who presented a transient complete atrioventricular block, and later a
      transient right bundle branch block and a left anterior hemiblock, following a
      nonpenetrating chest trauma due to a car accident. The difficulty for diagnosing
      myocardial contusion is pointed out, and the usefulness of the
      electrophysiological study for detecting baseline conduction system disorders is
      discussed.

PMID- 11591306
TI  - [Hemarthrosis as a hemorrhagic complication after thrombolytic treatment].
AB  - Hemorrhage of variable severity is the main complication of thrombolytic
      treatment. We present the case of a rare hemorrhagic location after the use of
      this treatment for acute myocardial infarction, as ankle hemarthrosis. In the
      first twelve hours the patient had a joint hemorrhagic effusion with refractory
      pain and arthrocentesis was required. Recurrence occurred while receiving heparin
      and after discontinuation of heparin perfusion stopped the patient developed
      occlusion of the coronary artery related to the infarct requiring emergency
      angioplasty. We discuss the severity and possible treatment of this situation.

PMID- 11591307
TI  - [Surgical treatment of atrial fibrillation and coronary artery bypass without the
      use of extracorporeal circulation: case report].
AB  - A 71-year-old man presented stable angina due to severe coronariophaty and
      chronic atrial fibrillation. A radial approach for atrial fibrillation and three
      coronary artery bypass grafts were performed without cardiopulmonary bypass. The
      procedure for the arrhythmia ablation was done epicardially with a multipolar
      radiofrequency catheter. Intraoperatively, the patient regained normal sinus
      rhythm, with an uneventful postoperative course. Postoperative echocardiography
      demonstrated the presence of an atrial A wave.

PMID- 11591308
TI  - [Transesophageal echocardiographic diagnosis of a ruptured sinus of valsalva
      aneurysm with right atrium fistula].
AB  - Congenital aneurysms of the sinus of Valsalva are relatively rare, tending to be
      most frequent in adults. Untreated, there is a substantial risk of complication
      due to bacterial endocarditis and, if rupture occurs, rapid and progressive
      cardiac insufficiency is fatal at short term. We report the case of a 53-year-old
      male with a ruptured right sinus of Valsalva aneurysm, resulting in an anomalous
      right atrium fistula. Symptoms presented, clinical diagnosis and, above all,
      transesophageal echocardiography were crucial in the final diagnosis leading to
      an early and satisfactory surgical intervention. Catheterization and angiography
      were not definitive. Echocardiographic data are described and a bibliography of
      relevant research articles is provided.

PMID- 11591309
TI  - [Prevalence of atrial fibrillation in the province of Girona, Spain: the REGICOR
      study].

PMID- 11591313
TI  - [Clopidogrel in acute coronary syndromes with non-ST elevation. Clinical
      implications of the CURE trial].
AB  - The pivotal role of the platelets in the genesis of acute coronary syndromes
      emphasises the importance of an early and sustained antiplatelet therapy. The
      CURE trial shows that clopidogrel in addition to aspirin achieves this double
      goal, with a 20% relative risk reduction in the primary composite endpoint of
      cardiovascular death, myocardial infarction or stroke in the first 30 days. The
      benefits are apparent as early as the first 24 hours of starting the treatment.
      There is also a consistent benefit of clopidogrel across all groups, including
      both high-risk and low-risk patients, which overrides an excess of 6 out of a
      thousand cases treated per year of bleeds, which require transfusion. Several
      clinical implications of the CURE trial are analyzed: the kind of patients who
      benefit more on clopidogrel, how long should treatment with clopidogrel continue,
      cost-benefit consideration, the impact of the findings on the benefit of the use
      of clopidogrel, on the use of glycoprotein IIb/IIIa receptor antagonists,
      clopidogrel pretreatment and long term therapy in patients undergoing
      percutaneous coronary intervention and bleeding risk with surgery.

PMID- 11591314
TI  - [Inflammation and acute coronary syndromes].
AB  - A great variety of stimuli, such as free radicals, oxidized LDL or some bacteria
      or virus infections, can act upon the vascular surface and lead to the
      development of an acute inflammatory reaction. There is more and more evidence
      supporting the hypothesis that the mechanism responsible for the transformation
      of a non-complicated atherosclerotic lesion into an hemorrhagic and ulcerated
      lesion, with the subsequent acute and unstable clinical status, is due to the
      onset of an inflammatory reaction. Many studies have tried to investigate the
      presence of any systemic marker able to predict the prognosis of patients at risk
      from developing acute events, and to distinguish them from those in stable
      status. The increase of the levels of C-reactive-protein has been related to the
      development of acute coronary syndromes, though often the results obtained in the
      different studies have had a quite poor prognostic value when applied to the
      general population. The lack of direct association between the increase of the
      levels of C-reactive-protein and Troponin I seems to rule out the possibility
      that the inflammatory stimulus might be the consequence of an irreversible
      injury, even though there is no doubt that severe ischemia is likely to play an
      active role in this sense.

PMID- 11591315
TI  - Convergence of distinct pathways to heart patterning revealed by the small
      molecule concentramide and the mutation heart-and-soul.
AB  - BACKGROUND: One of the earliest steps in heart formation is the generation of two
      chambers, as cardiogenic cells deployed in the epithelial sheet of mesoderm
      converge to form the nascent heart tube. What guides this transformation to
      organotypic form is not known. RESULTS: We have identified a small molecule,
      concentramide, and a genetic mutation called heart-and-soul (has) that disrupt
      heart patterning. Both cause the ventricle to form within the atrium. Here, we
      show that the has gene encodes PKC lambda. The effect of the has mutation is to
      disrupt epithelial cell-cell interactions in a broad range of tissues.
      Concentramide does not disrupt epithelial interactions, but rather shifts the
      converging heart field rostrally. What is shared between the concentramide and
      has effects is a reversal of the order of fusion of the anterior and posterior
      ends of the heart field. CONCLUSIONS: The polarity of cardiac tube assembly is a
      critical determinant of chamber orientation and is controlled by at least two
      distinct molecular pathways. Combined chemical/genetic dissection can identify
      nodal points in development, of special importance in understanding the complex
      patterning events of organogenesis.

PMID- 11591316
TI  - Positional cloning of heart and soul reveals multiple roles for PKC lambda in
      zebrafish organogenesis.
AB  - BACKGROUND: The Par-3/Par-6/aPKC complex is a key regulator of cell polarity in a
      number of systems. In Drosophila, this complex acts at the zonula adherens
      (adherens junctions) to establish epithelial polarity and helps to orient the
      mitotic spindle during asymmetric neuroblast divisions. In MDCKII cells, this
      complex localizes to the zonula occludens (tight junctions) and appears to
      regulate epithelial polarity. However, the in vivo role of this complex during
      vertebrate embryogenesis is not known, due to the lack of relevant mutations.
      RESULTS: We have positionally cloned the zebrafish heart and soul (has) mutation,
      which affects the morphogenesis of several embryonic tissues, and show that it
      encodes atypical protein kinase C lambda (aPKC lambda). We find that loss of aPKC
      lambda affects the formation and maintenance of the zonula adherens in the
      polarized epithelia of the retina, neural tube, and digestive tract, leading to
      novel phenotypes, such as the formation of multiple lumens in the developing
      intestine. In addition, has mutants display defects in gut looping and endodermal
      organ morphogenesis that appear to be independent of the defects in epithelial
      polarity. Finally, we show that loss of aPKC lambda leads to defects in spindle
      orientation during progenitor cell divisions in the neural retina. CONCLUSIONS:
      Our results show that aPKC lambda is required for the formation and maintenance
      of the zonula adherens during early epithelial development in vertebrates and
      demonstrate a previously undescribed yet critical role for this protein in organ
      morphogenesis. Furthermore, our studies identify the first genetic locus
      regulating the orientation of cell division in vertebrates.

PMID- 11591317
TI  - Kif1C, a kinesin-like motor protein, mediates mouse macrophage resistance to
      anthrax lethal factor.
AB  - BACKGROUND: Inbred mouse strains exhibit striking differences in the
      susceptibility of their macrophages to the effects of anthrax lethal toxin
      (LeTx). Previous data has shown that this difference in susceptibility lies
      downstream of toxin entry into macrophages. A locus controlling this phenotype,
      called Ltxs1, has been mapped to chromosome 11, but the responsible gene has not
      been identified. RESULTS: Here, we report the identification of the Ltxs1 gene as
      Kif1C, which encodes a kinesin-like motor protein of the UNC104 subfamily. Kif1C
      is the only gene in the Ltxs1 interval exhibiting polymorphisms between
      susceptible and resistant strains. Multiple alleles of Kif1C determine the
      susceptibility or resistance of cultured mouse macrophages to LeTx. Treatment of
      resistant macrophages with brefeldin-A (which alters the cellular localization of
      Kif1C) induces susceptibility to LeTx, while ectopic expression of a resistance
      allele of Kif1C in susceptible macrophages causes a 4-fold increase in the number
      of cells surviving LeTx treatment. We also show that cleavage of map kinase
      kinase 3, a target of LeTx proteolysis, occurs in resistant cells. CONCLUSIONS:
      We conclude that mutations in Kif1C are responsible for the differences in the
      susceptibility of inbred mouse macrophages to LeTx and that proper Kif1C function
      is required for LeTx resistance. Since the LeTx-mediated proteolysis of map
      kinase kinase 3 occurs even in resistant cells, Kif1C does not affect cellular
      entry or processing of LeTx and likely influences events occurring later in the
      intoxication pathway.

PMID- 11591318
TI  - A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic
      spindle.
AB  - Pin2/TRF1 was independently identified as a telomeric DNA binding protein (TRF1)
      [1] and as a protein (Pin2) that can bind the mitotic kinase NIMA and suppress
      its ability to induce mitotic catastrophe [2, 3]. Pin2/TRF1 has been shown to
      bind telomeric DNA as a dimer [3-7] and to negatively regulate telomere length [8
      11]. Interestingly, Pin2/TRF1 levels are regulated during the cell cycle, being
      increased in late G2 and mitosis and degraded as cells exit from mitosis [3].
      Furthermore, overexpression of Pin2/TRF1 induces mitotic entry and then apoptosis
      [12]. This Pin2/TRF1 activity can be significantly potentiated by the microtubule
      disrupting agent nocodazole [12] but is suppressed by phosphorylation of
      Pin2/TRF1 by ATM; this negative regulation is important for preventing apoptosis
      upon DNA damage [13]. These results suggest a role for Pin2/TRF1 in mitosis.
      However, nothing is known about how Pin2/TRF1 is involved in mitotic progression.
      Here, we describe a surprising physical interaction between Pin2/TRF1 and
      microtubules in a cell cycle-specific manner. Both expressed and endogenous
      Pin2/TRF1 proteins were localized to the mitotic spindle during mitosis.
      Furthermore, Pin2/TRF1 directly bound microtubules via its C-terminal domain.
      Moreover, Pin2/TRF1 also promoted microtubule polymerization in vitro. These
      results demonstrate for the first time a specific interaction between Pin2/TRF1
      and microtubules in a mitosis-specific manner, and they suggest a new role for
      Pin2/TRF1 in modulating the function of microtubules during mitosis.

PMID- 11591319
TI  - The OLD-1 positive regulator of longevity and stress resistance is under DAF-16
      regulation in Caenorhabditis elegans.
AB  - Aging and limited life span are fundamental biological phenomena observed in a
      variety of species [1]. Approximately 55 genes have been identified that can
      extend longevity when altered in Caenorhabditis elegans [2-5]. These genes
      include an insulin-like receptor (daf-2) and a phosphatidylinositol 3-OH kinase
      (age-1) regulating a forkhead transcription factor (daf-16) [6, 7], as well as
      genes mediating metabolic throughput [8], sensory perception [9], and
      reproduction [10]. Moreover, these mutant alleles both extend life span and
      increase resistance to ultraviolet (UV) radiation [11], heat [12], and oxidative
      stress [13-15], though the stress resistance of clk-1 is controversial. With the
      exception of old-1 and perhaps some other genes [16-19], all of the life
      extension alleles are hypomorphic or nullomorphic. Here, we show that the OLD-1
      transmembrane tyrosine kinase (formerly TKR-1; [16, 20]) is expressed in a
      variety of tissues, is stress inducible, and is a positive regulator of longevity
      and stress resistance. The transcription of old-1 is upregulated in long-lived
      age-1 and daf-2 mutants and is upregulated in response to heat, UV light, and
      starvation. Both RT-PCR and analysis of an OLD-1::GFP tag suggest that old-1
      expression is dependent on daf-16. Importantly, old-1 is required for the life
      extension of age-1 and daf-2 mutants. This study reveals a new system for
      specifying longevity and stress resistance and suggests possible mechanisms for
      mediating life extension by dietary restriction and hormesis.

PMID- 11591320
TI  - Visualization of mPer1 transcription in vitro: NMDA induces a rapid phase shift
      of mPer1 gene in cultured SCN.
AB  - Many physiological and behavioral phenomena are controlled by an internal, self
      sustaining oscillator with a periodicity of approximately 24 hr. In mammals, the
      principal oscillator resides in the suprachiasmatic nucleus (SCN). A light pulse
      during the subjective night causes a phase shift of the circadian rhythm via
      direct glutamatergic retinal afferents to the SCN [1]. Along with the accepted
      theoretical models of the clock, it is suggested that behavioral resetting of
      mammals is completed within 2 hr [2]; however, the molecular mechanism has not
      been elucidated. Here, we show the real-time image of the transcription of the
      circadian-clock gene mPer1 in the cultured SCN by using the transgenic mice that
      carry a luciferase reporter gene under the control of the mPer1 promoter [3]. The
      real-time image demonstrates that the mPer1 promoter activity oscillates robustly
      in a circadian manner and that this promoter activity is reset rapidly (within 2
      3 hr) when a phase shift occurs.

PMID- 11591321
TI  - When more means less: neural activity related to unsuccessful memory encoding.
AB  - The neural correlates of memory encoding have been studied by contrasting neural
      activity elicited by items at the time of learning according to whether they were
      later remembered or forgotten [1]. Previous studies have focused on regions where
      neural activity is greater for subsequently remembered items [2-8]. Here, we
      describe regions where activity is greater for subsequently forgotten items. In
      two experiments that employed the same incidental learning task, activity in an
      overlapping set of cortical regions (posterior cingulate, inferior and medial
      parietal, and dorsolateral prefrontal) was associated with failure on a
      subsequent memory test.

PMID- 11591322
TI  - Insertional polymorphisms of full-length endogenous retroviruses in humans.
AB  - Human endogenous retrovirus K (HERV-K) is distinctive among the retroviruses in
      the human genome in that many HERV-K proviruses were inserted into the human
      germline after the human and chimpanzee lineages evolutionarily diverged [1, 2].
      However, all full-length endogenous retroviruses described to date in humans are
      sufficiently old that all humans examined were homozygous for their presence [1].
      Moreover, none are intact; all have lethal mutations [1, 3, 4]. Here, we describe
      the first endogenous retroviruses in humans for which both the full-length
      provirus and the preintegration site alleles are shown to be present in the human
      population today. One provirus, called HERV-K113, was present in about 30% of
      tested individuals, while a second, called HERV-K115, was found in about 15%.
      HERV-K113 has full-length open reading frames (ORFs) for all viral proteins and
      lacks any nonsynonymous substitutions in amino acid motifs that are well
      conserved among retroviruses. This is the first such endogenous retrovirus
      identified in humans. These findings indicate that HERV-K remained capable of
      reinfecting humans through very recent evolutionary times and that HERV-K113 is
      an excellent candidate for an endogenous retrovirus that is capable of
      reinfecting humans today.

PMID- 11591323
TI  - Cdc42, dynein, and dynactin regulate MTOC reorientation independent of Rho
      regulated microtubule stabilization.
AB  - In migrating adherent cells such as fibroblasts and endothelial cells, the
      microtubule-organizing center (MTOC) reorients toward the leading edge [1-3].
      MTOC reorientation repositions the Golgi toward the front of the cell [1] and
      contributes to directional migration [4]. The mechanism of MTOC reorientation and
      its relation to the formation of stabilized microtubules (MTs) in the leading
      edge, which occurs concomitantly with MTOC reorientation [3], is unknown. We show
      that serum and the serum lipid, lysophosphatidic acid (LPA), increased Cdc42 GTP
      levels and triggered MTOC reorientation in serum-starved wounded monolayers of
      3T3 fibroblasts. Cdc42, but not Rho or Rac, was both sufficient and necessary for
      LPA-stimulated MTOC reorientation. MTOC reorientation was independent of Cdc42
      induced changes in actin and was not blocked by cytochalasin D. Inhibition of
      dynein or dynactin blocked LPA- and Cdc42-stimulated MTOC reorientation. LPA also
      stimulates a Rho/mDia pathway that selectively stabilizes MTs in the leading edge
      [5, 6]; however, activators and inhibitors of MTOC reorientation and MT
      stabilization showed that each response was regulated independently. These
      results establish an LPA/Cdc42 signaling pathway that regulates MTOC
      reorientation in a dynein-dependent manner. MTOC reorientation and MT
      stabilization both act to polarize the MT array in migrating cells, yet these
      processes act independently and are regulated by separate Rho family GTPase
      signaling pathways.

PMID- 11591324
TI  - Delayed and incomplete reprogramming of chromosome methylation patterns in bovine
      cloned embryos.
AB  - Full-term development has now been achieved in several mammalian species by
      transfer of somatic nuclei into enucleated oocytes [1, 2]. Although a high
      proportion of such reconstructed embryos can evolve until the blastocyst stage,
      only a few percent develop into live offspring, which often exhibit developmental
      abnormalities [3, 4]. Regulatory epigenetic markers such as DNA methylation are
      imposed on embryonic cells as normal development proceeds, creating
      differentiated cell states. Cloned embryos require the erasure of their somatic
      epigenetic markers so as to regain a totipotent state [5]. Here we report on
      differences in the dynamics of chromosome methylation between cloned and normal
      bovine embryos before implantation. We show that cloned embryos fail to reproduce
      distinguishable parental-chromosome methylation patterns after fusion and
      maintain their somatic pattern during subsequent stages, mainly by a highly
      reduced efficiency of the passive demethylation process. Surprisingly,
      chromosomes appear constantly undermethylated on euchromatin in morulae and
      blastocysts, while centromeric heterochromatin remains more methylated than that
      of normal embryos. We propose that the abnormal time-dependent methylation events
      spanning the preimplantation development of clones may significantly interfere
      with the epigenetic reprogramming, contributing to the high incidence of
      physiological anomalies occurring later during pregnancy or after clone birth.

PMID- 11591325
TI  - Identification of a novel receptor for B lymphocyte stimulator that is mutated in
      a mouse strain with severe B cell deficiency.
AB  - BLyS (also called BAFF, TALL-1, THANK, and zTNF4), a TNF superfamily member,
      binds two receptors, TACI and BCMA, and regulates humoral immune responses [1-7].
      These two receptors also bind APRIL [7-10], another TNF superfamily member. The
      results from TACI(-/-) and BCMA(-/-) mice suggest the existence of additional
      receptor(s) for BLyS. The TACI knockout gives the paradoxical result of B cells
      being hyperresponsive, suggesting an inhibitory role for this receptor [11, 12],
      while BCMA null mice have no discernable phenotype [13]. Here we report the
      identification of a third BLyS receptor (BR3; BLyS receptor 3). This receptor is
      unique in that, in contrast to TACI and BCMA, BR3 only binds BLyS. Treatment of
      antigen-challenged mice with BR3-Fc inhibited antibody production, indicating an
      essential role for BLyS, but not APRIL, in this response. A critical role for BR3
      in B cell ontogeny is underscored by our data showing that the BR3 gene had been
      inactivated by a discrete, approximately 4.7 kb gene insertion event that
      disrupted the 3' end of the BR3 gene in A/WySnJ mice, which lack peripheral B
      cells.

PMID- 11591326
TI  - Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells.
AB  - The resetting of a somatic epigenotype to a totipotential state has been
      demonstrated by successful animal cloning, via transplantation of somatic nuclei
      into enucleated oocytes. We have established an experimental system, which
      reproduces the nuclear reprogramming of somatic cells in vitro by fusing adult
      thymocytes with embryonic stem (ES) cells. Analysis of the lymphoid-cell-specific
      V-(D)-J DNA rearrangement of the T cell receptor and immunoglobin genes shows
      that the ES cells have hybridized with differentiated cells. In these ES cell
      hybrids, the inactivated X chromosome derived from a female thymocyte adopts some
      characteristics of an active X chromosome, including early replication timing and
      unstable Xist transcription. We also found that an Oct4-GFP transgene, which is
      normally repressed in thymocytes, is reactivated 48 hr after cell fusion. The
      pluripotency of the ES-thymocyte hybrid cells is shown in vivo, since they
      contribute to all three primary germ layers of chimeric embryos. The somatic DNA
      methylation pattern of the imprinted H19 and Igf2r genes is maintained in these
      hybrids, unlike hybrids between ES and EG (embryonic germ) cells in which the
      differential methylation is erased. Thus, ES cells have the capacity to reset
      certain aspects of the epigenotype of somatic cells to those of ES cells.

PMID- 11591327
TI  - Plaudits for stem cell pioneers.

PMID- 11591328
TI  - Humans seek clues from closest kin.
AB  - Genomes: As researchers promote the value of different species in the competition
      for rare sequencing dollars, primate genomics can still make a case in the appeal
      for those funds, reports Heather Dawes.

PMID- 11591331
TI  - Cortical cartography: what's in a map?

PMID- 11591332
TI  - Why do regulators of apoptosis look like bacterial toxins?

PMID- 11591333
TI  - Wakefulness: an eye-opening perspective on orexin neurons.
AB  - Orexin-containing neurons regulate wakefulness, and loss of orexin produces
      narcolepsy. Recent studies of mice lacking orexin neurons have shown that these
      cells also play essential roles in the control of feeding and energy balance.

PMID- 11591335
TI  - Visual perception: sunny side up.
AB  - Illumination, both natural and artificial, typically comes from above. Neurons in
      visual area V4--part of the object-processing pathway in the primate brain--may
      rely on this anisotropy to infer three-dimensional structure from shading cues.

PMID- 11591334
TI  - RNA interference: it's a small RNA world.
AB  - Short RNAs regulate gene expression in many species. Some are generated from any
      double-stranded RNA and degrade complementary RNAs; others are encoded by genes
      and repress specific mRNAs. Both, it turns out, are processed and handled by
      similar proteins. These pathways offer a glimpse into a world of small RNAs.

PMID- 11591336
TI  - Drosophila oogenesis: coordinating germ line and soma.
AB  - A new function for Delta-Notch signaling has been discovered in Drosophila
      oogenesis: Delta expressed in the germ cells activates Notch in the surrounding
      somatic follicle cells to control their differentiation, proliferation and
      morphogenesis.

PMID- 11591337
TI  - Hearing: cortical activation does matter.
AB  - Lesion studies have suggested that the auditory cortex may not be involved in
      many aspects of hearing. A recent report casts doubt on this long-held view by
      showing that reversible inactivation of the auditory cortex leads to a transient
      impairment in tone detection and frequency discrimination.

PMID- 11591338
TI  - Plant meristems: a menage a trois to end it all.
AB  - Regulated termination of stem cell maintenance is required to complete
      reproductive development in plants. Two recent studies have revealed a new
      relationship for some old suspects; the WUSCHEL gene, which promotes
      indeterminancy, is involved as well as the floral regulators LEAFY and AGAMOUS.

PMID- 11591339
TI  - Synaptic plasticity: a molecular memory switch.
AB  - Recent work shows that two molecules with major roles in synaptic plasticity-
      CaMKII and the NMDA receptor--bind to each other. This binding activates CaMKII
      and triggers its autophosphorylation. In this state, it may act as a memory
      switch and strengthen synapses through enzymatic and structural processes.

PMID- 11591340
TI  - Adhesion signaling: how beta-catenin interacts with its partners.
AB  - The multi-functional protein beta-catenin plays essential roles in cell-cell
      adhesion and nuclear signaling. Elucidation of the structures of beta-catenin
      complexes is beginning to clarify how beta-catenin uses the same surface to bind
      its various partners, and provides insights into how these interactions might be
      regulated.

PMID- 11591341
TI  - Apoptotic cell removal.
AB  - Ingestion by professional or amateur phagocytes is the fate of most cells that
      undergo apoptosis. Studies in both Caenorhabditis elegans and mammals are now
      converging to reveal some of the key mechanisms and consequences of this removal
      process. At least seven corpse removal genes in nematodes have mammalian
      equivalents, and represent elements of signaling pathways involved in uptake. In
      mammals, a wide variety of apoptotic cell recognition receptors has been
      implicated and appears to be divided into two categories, involved in tethering
      the apoptotic cell or triggering an uptake mechanism related to macropinocytosis.
      Apoptotic cell removal is normally efficient and non-inflammatory. By contrast,
      the process may become subverted by parasites to yield a more favorable growth
      environment, or in other cases lead to fibrosis. Removal may also clinch the
      apoptotic process itself in cells not yet completely committed to death.

PMID- 11591342
TI  - A Ku bridge over broken DNA.
AB  - The Ku heterodimer is essential for the nonhomologous end-joining pathway of DNA
      double-strand break repair; it both protects the broken ends and recruits some of
      the many proteins required to complete repair. The recently determined structure
      of Ku provides insights into how it can both bind to the DNA ends and allow
      access by the other proteins required to rejoin them.

PMID- 11591345
TI  - Structure of a conjugating enzyme-ubiquitin thiolester intermediate reveals a
      novel role for the ubiquitin tail.
AB  - BACKGROUND: Ubiquitin-conjugating enzymes (E2s) are central enzymes involved in
      ubiquitin-mediated protein degradation. During this process, ubiquitin (Ub) and
      the E2 protein form an unstable E2-Ub thiolester intermediate prior to the
      transfer of ubiquitin to an E3-ligase protein and the labeling of a substrate for
      degradation. A series of complex interactions occur among the target substrate,
      ubiquitin, E2, and E3 in order to efficiently facilitate the transfer of the
      ubiquitin molecule. However, due to the inherent instability of the E2-Ub
      thiolester, the structural details of this complex intermediate are not known.
      RESULTS: A three-dimensional model of the E2-Ub thiolester intermediate has been
      determined for the catalytic domain of the E2 protein Ubc1 (Ubc1(Delta450)) and
      ubiquitin from S. cerevisiae. The interface of the E2-Ub intermediate was
      determined by kinetically monitoring thiolester formation by 1H-(15)N HSQC
      spectra by using combinations of 15N-labeled and unlabeled Ubc1(Delta450) and Ub
      proteins. By using the surface interface as a guide and the X-ray structures of
      Ub and the 1.9 A structure of Ubc1(Delta450) determined here, docking simulations
      followed by energy minimization were used to produce the first model of a E2-Ub
      thiolester intermediate. CONCLUSIONS: Complementary surfaces were found on the E2
      and Ub proteins whereby the C terminus of Ub wraps around the E2 protein
      terminating in the thiolester between C88 (Ubc1(Delta450)) and G76 (Ub). The
      model supports in vivo and in vitro experiments of E2 derivatives carrying
      surface residue substitutions. Furthermore, the model provides insights into the
      arrangement of Ub, E2, and E3 within a ternary targeting complex.

PMID- 11591344
TI  - Structural basis of HIV-1 and HIV-2 protease inhibition by a monoclonal antibody.
AB  - BACKGROUND: Since the demonstration that the protease of the human
      immunodeficiency virus (HIV Pr) is essential in the viral life cycle, this enzyme
      has become one of the primary targets for antiviral drug design. The murine
      monoclonal antibody 1696 (mAb1696), produced by immunization with the HIV-1
      protease, inhibits the catalytic activity of the enzyme of both the HIV-1 and HIV
      2 isolates with inhibition constants in the low nanomolar range. The antibody
      cross-reacts with peptides that include the N terminus of the enzyme, a region
      that is highly conserved in sequence among different viral strains and that,
      furthermore, is crucial for homodimerization to the active enzymatic form.
      RESULTS: We report here the crystal structure at 2.7 A resolution of a
      recombinant single-chain Fv fragment of mAb1696 as a complex with a cross
      reactive peptide of the HIV-1 protease. The antibody-antigen interactions
      observed in this complex provide a structural basis for understanding the origin
      of the broad reactivity of mAb-1696 for the HIV-1 and HIV-2 proteases and their
      respective N-terminal peptides. CONCLUSION: A possible mechanism of HIV-protease
      inhibition by mAb1696 is proposed that could help the design of inhibitors aimed
      at binding inactive monomeric species.

PMID- 11591346
TI  - Free-energy calculations highlight differences in accuracy between X-ray and NMR
      structures and add value to protein structure prediction.
AB  - BACKGROUND: While X-ray crystallography structures of proteins are considerably
      more reliable than those from NMR spectroscopy, it has been difficult to assess
      the inherent accuracy of NMR structures, particularly the side chains. RESULTS:
      For 15 small single-domain proteins, we used a molecular mechanics-/dynamics
      based free-energy approach to investigate native, decoy, and fully extended alpha
      conformations. Decoys were all less energetically favorable than native
      conformations in nine of the ten X-ray structures and in none of the five NMR
      structures, but short 150 ps molecular dynamics simulations on the experimental
      structures caused them to have the lowest predicted free energy in all 15
      proteins. In addition, a strong correlation exists (r(2) = 0.86) between the
      predicted free energy of unfolding, from native to fully extended conformations,
      and the number of residues. CONCLUSIONS: This work suggests that the approximate
      treatment of solvent used in solving NMR structures can lead NMR model
      conformations to be less reliable than crystal structures. This conclusion was
      reached because of the considerably higher calculated free energies and the
      extent of structural deviation during aqueous dynamics simulations of NMR models
      compared to those determined by X-ray crystallography. Also, the strong
      correlation found between protein length and predicted free energy of unfolding
      in this work suggests, for the first time, that a free-energy function can allow
      for identification of the native state based on calculations on an extended state
      and in the absence of an experimental structure.

PMID- 11591347
TI  - Combined EM/X-ray imaging yields a quasi-atomic model of the adenovirus-related
      bacteriophage PRD1 and shows key capsid and membrane interactions.
AB  - BACKGROUND: The dsDNA bacteriophage PRD1 has a membrane inside its icosahedral
      capsid. While its large size (66 MDa) hinders the study of the complete virion at
      atomic resolution, a 1.65-A crystallographic structure of its major coat protein,
      P3, is available. Cryo-electron microscopy (cryo-EM) and three-dimensional
      reconstruction have shown the capsid at 20-28 A resolution. Striking
      architectural similarities between PRD1 and the mammalian adenovirus indicate a
      common ancestor. RESULTS: The P3 atomic structure has been fitted into improved
      cryo-EM reconstructions for three types of PRD1 particles: the wild-type virion,
      a packaging mutant without DNA, and a P3-shell lacking the membrane and the
      vertices. Establishing the absolute EM scale was crucial for an accurate match.
      The resulting "quasi-atomic" models of the capsid define the residues involved in
      the major P3 interactions, within the quasi-equivalent interfaces and with the
      membrane, and show how these are altered upon DNA packaging. CONCLUSIONS: The new
      cryo-EM reconstructions reveal the structure of the PRD1 vertex and the
      concentric packing of DNA. The capsid is essentially unchanged upon DNA
      packaging, with alterations limited to those P3 residues involved in membrane
      contacts. These are restricted to a few of the N termini along the icosahedral
      edges in the empty particle; DNA packaging leads to a 4-fold increase in the
      number of contacts, including almost all copies of the N terminus and the loop
      between the two beta barrels. Analysis of the P3 residues in each quasi
      equivalent interface suggests two sites for minor proteins in the capsid edges,
      analogous to those in adenovirus.

PMID- 11591348
TI  - Solution structure of a cyanovirin-N:Man alpha 1-2Man alpha complex: structural
      basis for high-affinity carbohydrate-mediated binding to gp120.
AB  - BACKGROUND: Cyanovirin-N (CVN) is a novel, 11 kDa cyanobacterial protein that
      potently inhibits viral entry by diverse strains of HIV through high-affinity
      carbohydrate-mediated interactions with the viral envelope glycoprotein gp120.
      CVN contains two symmetry-related carbohydrate binding sites of differing
      affinities that selectively bind to Man(8) D1D3 and Man(9) with nanomolar
      affinities, the carbohydrates that also mediate CVN:gp120 binding. High
      resolution structural studies of CVN in complex with a representative
      oligosaccharide are desirable for understanding the structural basis for this
      unprecedented specificity. RESULTS: We have determined by multidimensional
      heteronuclear NMR spectroscopy the three-dimensional solution structure of CVN in
      complex with two equivalents of the disaccharide Manalpha1-2Manalpha, a high
      affinity ligand which represents the terminal-accessible disaccharide present in
      Man(8) D1D3 and Man(9). The structure reveals that the bound disaccharide adopts
      the stacked conformation, thereby explaining the selectivity for Man(8) D1D3 and
      Man(9) over other oligomannose structures, and presents two novel carbohydrate
      binding sites that account for the differing affinities of the two sites. The
      high-affinity site comprises a deep pocket that nearly envelops the disaccharide,
      while the lower-affinity site comprises a semicircular cleft that partially
      surrounds the disaccharide. The approximately 40 A spacing of the two binding
      sites provides a simple model for CVN:gp120 binding. CONCLUSIONS: The
      CVN:Manalpha1-2Manalpha complex provides the first high-resolution structure of a
      mannose-specific protein-carbohydrate complex with nanomolar affinity and
      presents a new carbohydrate binding motif, as well as a new class of carbohydrate
      binding protein, that facilitates divalent binding via a monomeric protein.

PMID- 11591349
TI  - Structure of E. coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase
      reveals similarity to the purine nucleoside phosphorylases.
AB  - BACKGROUND: 5'-methylthioadenosine/S-adenosyl-homocysteine (MTA/AdoHcy)
      nucleosidase catalyzes the irreversible cleavage of 5'-methylthioadenosine and S
      adenosylhomocysteine to adenine and the corresponding thioribose, 5'
      methylthioribose and S-ribosylhomocysteine, respectively. While this enzyme is
      crucial for the metabolism of AdoHcy and MTA nucleosides in many prokaryotic and
      lower eukaryotic organisms, it is absent in mammalian cells. This metabolic
      difference represents an exploitable target for rational drug design. RESULTS:
      The crystal structure of E. coli MTA/AdoHcy nucleosidase was determined at 1.90 A
      resolution with the multiwavelength anomalous diffraction (MAD) technique. Each
      monomer of the MTA/AdoHcy nucleosidase dimer consists of a mixed alpha/beta
      domain with a nine-stranded mixed beta sheet, flanked by six alpha helices and a
      small 3(10) helix. Intersubunit contacts between the two monomers present in the
      asymmetric unit are mediated primarily by helix-helix and helix-loop hydrophobic
      interactions. The unexpected presence of an adenine molecule in the active site
      of the enzyme has allowed the identification of both substrate binding and
      potential catalytic amino acid residues. CONCLUSIONS: Although the sequence of E.
      coli MTA/AdoHcy nucleosidase has almost no identity with any known enzyme, its
      tertiary structure is similar to both the mammalian (trimeric) and prokaryotic
      (hexameric) purine nucleoside phosphorylases. The structure provides evidence
      that this protein is functional as a dimer and that the dual specificity for MTA
      and AdoHcy results from the truncation of a helix. The structure of MTA/AdoHcy
      nucleosidase is the first structure of a prokaryotic nucleoside N-ribohydrolase
      specific for 6-aminopurines.

PMID- 11591350
TI  - Crystal structure of bisphosphorylated IGF-1 receptor kinase: insight into domain
      movements upon kinase activation.
AB  - BACKGROUND: The insulin-like growth-factor-1 (IGF-1) receptor, which is widely
      expressed in cells that have undergone oncogenic transformation, is emerging as a
      novel target in cancer therapy. IGF-1-induced receptor activation results in
      autophosphorylation of cytoplasmic kinase domains and enhances their capability
      to phosphorylate downstream substrates. Structures of the homologous insulin
      receptor kinase (IRK) exist in an open, unphosphorylated form and a closed,
      trisphosphorylated form. RESULTS: We have determined the 2.1 A crystal structure
      of the IGF-1 receptor protein tyrosine kinase domain phosphorylated at two
      tyrosine residues within the activation loop (IGF-1RK2P) and bound to an ATP
      analog. The ligand is not in a conformation compatible with phosphoryl transfer,
      and the activation loop is partially disordered. Compared to the homologous
      insulin receptor kinase, IGF-1RK2P is trapped in a half-closed, previously
      unobserved conformation. Observed domain movements can be dissected into two
      orthogonal rotational components. CONCLUSIONS: Conformational changes upon kinase
      activation are triggered by the degree of phosphorylation and are crucially
      dependent on the conformation of the proximal end of the kinase activation loop.
      This IGF-1RK structure will provide a molecular basis for the design of selective
      antioncogenic therapeutic agents.

PMID- 11591351
TI  - The structure of an engineered domain-swapped ribonuclease dimer and its
      implications for the evolution of proteins toward oligomerization.
AB  - BACKGROUND: Domain swapping has been proposed as a mechanism that explains the
      evolution from monomeric to oligomeric proteins. Bovine and human pancreatic
      ribonucleases are monomers with no biological properties other than their RNA
      cleavage ability. In contrast, the closely related bovine seminal ribonuclease is
      a natural domain-swapped dimer that has special biological properties, such as
      cytotoxicity to tumour cells. Several recombinant ribonuclease variants are
      domain-swapped dimers, but a structure of this kind has not yet been reported for
      the human enzyme. RESULTS: The crystal structure at 2 A resolution of an
      engineered ribonuclease variant called PM8 reveals a new kind of domain-swapped
      dimer, based on the change of N-terminal domains between the two subunits. The
      swapping is fastened at both hinge peptides by the newly introduced Gln101,
      involved in two intermolecular hydrogen bonds and in a stacking interaction
      between residues of different chains. Two antiparallel salt bridges and water
      mediated hydrogen bonds complete a new interface between subunits, while the
      hinge loop becomes organized in a 3(10) helix structure. CONCLUSIONS: Proteins
      capable of domain swapping may quickly evolve toward an oligomeric form. As shown
      in the present structure, a single residue substitution reinforces the quaternary
      structure by forming an open interface. An evolutionary advantage derived from
      the new oligomeric state will fix the mutation and favour others, leading to a
      more extended complementary dimerization surface, until domain swapping is no
      longer necessary for dimer formation. The newly engineered swapped dimer reported
      here follows this hypothetical pathway for the rapid evolution of proteins.

PMID- 11591352
TI  - Getting the adrenaline going: crystal structure of the adrenaline-synthesizing
      enzyme PNMT.
AB  - BACKGROUND: Adrenaline is localized to specific regions of the central nervous
      system (CNS), but its role therein is unclear because of a lack of suitable
      pharmacologic agents. Ideally, a chemical is required that crosses the blood
      brain barrier, potently inhibits the adrenaline-synthesizing enzyme PNMT, and
      does not affect other catecholamine processes. Currently available PNMT
      inhibitors do not meet these criteria. We aim to produce potent, selective, and
      CNS-active PNMT inhibitors by structure-based design methods. The first step is
      the structure determination of PNMT. RESULTS: We have solved the crystal
      structure of human PNMT complexed with a cofactor product and a submicromolar
      inhibitor at a resolution of 2.4 A. The structure reveals a highly decorated
      methyltransferase fold, with an active site protected from solvent by an
      extensive cover formed from several discrete structural motifs. The structure of
      PNMT shows that the inhibitor interacts with the enzyme in a different mode from
      the (modeled) substrate noradrenaline. Specifically, the position and orientation
      of the amines is not equivalent. CONCLUSIONS: An unexpected finding is that the
      structure of PNMT provides independent evidence of both backward evolution and
      fold recruitment in the evolution of a complex enzyme from a simple fold. The
      proposed evolutionary pathway implies that adrenaline, the product of PNMT
      catalysis, is a relative newcomer in the catecholamine family. The PNMT structure
      reported here enables the design of potent and selective inhibitors with which to
      characterize the role of adrenaline in the CNS. Such chemical probes could
      potentially be useful as novel therapeutics.

PMID- 11591353
TI  - Crystal structure of imidazole glycerol phosphate synthase: a tunnel through a
      (beta/alpha)8 barrel joins two active sites.
AB  - BACKGROUND: Imidazole glycerol phosphate synthase catalyzes a two-step reaction
      of histidine biosynthesis at the bifurcation point with the purine de novo
      pathway. The enzyme is a new example of intermediate channeling by glutamine
      amidotransferases in which ammonia generated by hydrolysis of glutamine is
      channeled to a second active site where it acts as a nucleophile. In this case,
      ammonia reacts in a cyclase domain to produce imidazole glycerol phosphate and an
      intermediate of purine biosynthesis. The enzyme is also a potential target for
      drug and herbicide development since the histidine pathway does not occur in
      mammals. RESULTS: The 2.1 A crystal structure of imidazole glycerol phosphate
      synthase from yeast reveals extensive interaction of the glutaminase and cyclase
      catalytic domains. At the domain interface, the glutaminase active site points
      into the bottom of the (beta/alpha)(8) barrel of the cyclase domain. An ammonia
      tunnel through the (beta/alpha)(8) barrel connects the glutaminase docking site
      at the bottom to the cyclase active site at the top. A conserved "gate" of four
      charged residues controls access to the tunnel. CONCLUSIONS: This is the first
      structure in which all the components of the ubiquitous (beta/alpha)(8) barrel
      fold, top, bottom, and interior, take part in enzymatic function. Intimate
      contacts between the barrel domain and the glutaminase active site appear to be
      poised for crosstalk between catalytic centers in response to substrate binding
      at the cyclase active site. The structure provides a number of potential sites
      for inhibitor development in the active sites and in a conserved interdomain
      cavity.

PMID- 11591354
TI  - Hypertension. Introduction.

PMID- 11591355
TI  - Efficacy of perindopril in the treatment of systemic hypertension.
AB  - The angiotensin-converting enzyme inhibitor, perindopril erbumine, has been
      approved for use in the United States only recently but has been studied
      extensively worldwide over the last decade. Placebo-controlled trials in a wide
      range of patients with hypertension, including the elderly, those with isolated
      systolic hypertension, and those with concomitant diseases such as
      hyperlipidemia, diabetes, cardiac arrhythmia, peripheral arterial occlusive
      disease, nephropathy with proteinuria, and chronic obstructive pulmonary disease,
      have shown that perindopril is highly effective in lowering both systolic and
      diastolic blood pressure (BP). Studies in which BP has been monitored for 24-hour
      intervals show that perindopril (1) has a gradual onset of action, (2) provides
      smooth BP control over its once-daily dosing interval, (3) has a trough-peak
      ratio of about 1, and (4) maintains its antihypertensive efficacy despite missed
      doses. Perindopril increases arterial compliance and reverses left ventricular
      hypertrophy in hypertensive patients. Both of these effects are at least partly
      independent of its ability to lower BP. Perindopril is safe and well tolerated in
      patients with hypertension. Rates of adverse events and discontinuation because
      of such events are low.

PMID- 11591356
TI  - Dosage considerations with perindopril for systemic hypertension.
AB  - Perindopril erbumine is a once-daily angiotensin-converting enzyme (ACE)
      inhibitor that effectively lowers systolic and diastolic blood pressure (BP) in
      patients with mild-to-moderate hypertension. Converted from the prodrug ester
      perindopril, the active diacid perindoprilat is distributed rapidly and
      extensively, primarily to tissues with high ACE activity. Its ability to lower BP
      is comparable to or better than that of other antihypertensive agents, both of
      its own class and other classes, and its trough-peak ratio is consistently
      between 75% and 100%, translating into 24 hours of true efficacy per dose. First
      dose hypotension caused by an initial acute BP depression occurs less frequently
      with perindopril than with other ACE inhibitors, an advantage in volume
      contracted patients and those whose BP is angiotensin II dependent, such as
      patients with congestive heart failure. A missed-dose study showed that most of
      the antihypertensive effect of perindopril remains for 24 to 48 hours after
      dosing, a characteristic that confers protection to patients who miss a dose.
      Perindopril improves the distensibility and compliance of large and small
      arteries, which are compromised in hypertension, and can effect vascular
      remodeling by a mechanism independent of BP lowering. The clinical implications
      of these effects are being investigated in large trials. Perindopril is well
      tolerated in the elderly, and combination therapy with a diuretic was shown to
      yield significant additional BP reduction. Perindoprilat is cleared renally;
      dosage should be adjusted in patients with renal impairment.

PMID- 11591357
TI  - Perindopril treatment for congestive heart failure.
AB  - Congestive heart failure (CHF) is the most common and lethal consequence of
      atherosclerotic cardiovascular disease, with a prevalence estimated between 1%
      and 10%, and very high associated mortality. Preventing the continued progression
      of established heart failure and improving the prognosis for patients with this
      disease is difficult, but angiotensin-converting enzyme (ACE) inhibitors have
      been shown to be effective in reducing mortality in patients with CHF. In a
      review of the worldwide literature of the efficacy and safety of perindopril
      erbumine for the treatment of patients with CHF, once-daily treatment with this
      ACE inhibitor was shown to be effective in patients with CHF of all severities.
      Its use is associated with a low risk of first-dose hypotension and no unwanted
      effects on blood pressure in normotensive patients. Perindopril also improves
      arterial compliance and reverses left ventricular hypertrophy in patients with
      hypertension. It is well tolerated and has no significant effects on heart rate,
      indexes of renal function, or plasma lipid profile. It also has no clinically
      significant interactions with other drugs, including digoxin, likely to be taken
      by patients with CHF.

PMID- 11591358
TI  - Effects of perindopril on cardiovascular remodeling.
AB  - The primary aim in the medical treatment of hypertension is to lower blood
      pressure (BP). A wide variety of agents have proved effective for meeting this
      goal. However, an ideal agent for management of hypertensive patients must also
      meet a number of additional criteria. It should have a significant positive
      impact on conditions that are likely to be associated with elevated BP and that
      are known risk factors for cardiovascular morbidity and mortality. This article
      reviews effects of the long-acting angiotensin-converting enzyme inhibitor
      perindopril erbumine on hypertension-associated blood vessel and myocardial
      remodeling known to be associated with increased cardiovascular risk. Long-term
      treatment with perindopril improves arterial compliance and increases the media
      lumen ratio of peripheral resistance vessels. These effects appear to be at least
      partially independent of BP lowering. Reversal of hypertension-associated
      vascular remodeling with perindopril should decrease afterload and reduce or
      reverse left ventricular hypertrophy. Evaluation of patients who have received
      long-term perindopril therapy has shown this to be the case. This effect of
      perindopril on an important predictor of cardiovascular morbidity and mortality
      may also be partially independent of BP. The combination of treatment with such
      agents as perindopril and methods that permit early detection of vascular changes
      contributing to cardiovascular disease has the potential to markedly improve the
      prognosis for hypertensive patients and others at risk for development of
      cardiovascular disease.

PMID- 11591359
TI  - Safety profile of perindopril.
AB  - Approximately 25% of US adults have high blood pressure (BP). Selection of
      effective and safe antihypertensive therapy for these individuals is an important
      health-care priority. High BP can be treated with a wide range of
      antihypertensive agents from a number of different classes. These drugs may
      differ in their suitability for administration to different subpopulations of
      patients. Results from both clinical trials and postmarketing surveillance
      indicate that the angiotensin-converting enzyme (ACE) inhibitor perindopril
      erbumine is safe and well tolerated in a wide range of patients with
      hypertension. Cough, the most common ACE inhibitor-associated side effect, is
      also the most common clinical adverse event reported for perindopril, but <2% of
      perindopril-treated patients discontinue therapy because of cough. Other adverse
      events often associated with ACE inhibitors, first-dose hypotension and
      hyperkalemia, appear to occur less often with perindopril than with other agents
      in this class. The favorable safety profile for perindopril extends to a wide
      range of patients, including the elderly and those with either heart failure or
      renal disease. Perindopril has no negative effects on lipids in patients with
      hyperlipidemia or on glycemic control in patients with type 2 diabetes mellitus,
      and it reduces proteinuria in patients with renal disease. Perindopril has no
      known clinically significant drug-drug interactions. Thus, perindopril is a safe
      BP-lowering agent with documented tolerability in a wide range of patients with
      hypertension.

PMID- 11591360
TI  - Cellular strategies for proteolytic targeting during migration and invasion.
AB  - Cell migration over or through the extracellular matrix (ECM) is an integral
      feature of both physiological and pathological processes. Regulation of the
      changing cell-ECM interactions involved can be effected by proteolysis and
      requires strict spatial and temporal targeting of proteinase activity. The
      versatile use of different proteinase systems, with a variety of localisation
      mechanisms and cleavage targets, is being revealed by a plethora of studies using
      in vitro models. This mini review reflects the status of our knowledge of
      strategies for the localisation of proteolytic activity effected during cell
      migration.

PMID- 11591361
TI  - The polymerization mechanism of the bacterial cell division protein FtsZ.
AB  - Bacteria and archaea usually divide symmetrically by formation of a septum in the
      middle of the cell. A key event in cell division is the assembly of the FtsZ
      ring. FtsZ is the prokaryotic homolog of tubulin and forms polymers in the
      presence of guanine nucleotides. Here, we specifically address the polymerization
      of FtsZ and the role of nucleotide hydrolysis in polymer formation and
      stabilization. Recent structural and biochemical results are discussed and a
      model for FtsZ polymerization, similar to that for tubulin, is presented.

PMID- 11591362
TI  - Endless healing: TGF-beta, SMADs, and fibrosis.

PMID- 11591363
TI  - Apigenin decreases expression of the myofibroblast phenotype.
AB  - We investigated the effect of the dietary flavonoid apigenin on myofibroblast
      function. We report that in myofibroblasts treated with apigenin, proliferation
      and basal levels of alpha1(I) collagen and alpha-smooth muscle actin mRNAs were
      markedly reduced. Apigenin also attenuated the transforming growth factor-beta
      stimulated increases of alpha1(I) collagen and alpha-smooth muscle actin mRNAs.
      Characterization of the apigenin effects indicates that apigenin reduces both the
      stability of the alpha1(I) collagen mRNA and the rate of transcription of the
      alpha1(I) collagen gene through a cycloheximide-sensitive pathway. Western blot
      analyses indicate that Akt activity is reduced in apigenin-treated
      myofibroblasts.

PMID- 11591364
TI  - Accelerated telomere shortening in Fanconi anemia fibroblasts--a longitudinal
      study.
AB  - Fanconi anemia (FA) is a fatal inherited disease displaying chromosomal
      instability, disturbances in oxygen metabolism and a high burden of intracellular
      radical oxygen species. Oxygen radicals can damage DNA including telomeric
      regions. Insufficient repair results in single strand breaks that can induce
      accelerated telomere shortening. In a longitudinal study we demonstrate that
      telomeric DNA is continuously lost at a higher rate in FA fibroblasts compared to
      healthy controls. Furthermore, we show that this loss is caused rather by an
      increased shortening per cell division in regularly replicating cells than by
      apoptosis.

PMID- 11591365
TI  - Genetic evidence that antibacterial activity of lysozyme is independent of its
      catalytic function.
AB  - A catalytically inactive mutant of hen egg white lysozyme was constructed by site
      directed mutagenesis to elucidate the role of enzymatic activity on its
      antimicrobial activity against Gram-positive bacteria. The catalytic residue
      aspartic acid at position 52 of lysozyme was substituted with serine (D52S-Lz)
      and the mutant cDNA was inserted into a yeast expression vector, pYES-2. Western
      blot analysis indicated that the mutation did not affect secretion of the D52S-Lz
      lysozyme into the medium of the expressing Saccharomyces cerevisiae, INVSC1. In
      addition, circular dichroism and fluorescence spectral analysis revealed no
      change in the structure of D52S-Lz compared to that of wild-type (Wt-Lz)
      lysozyme. The mutation (D52S) abolished the catalytic activity of lysozyme.
      Antimicrobial tests against Staphylococcus aureus and Bacillus subtilis revealed
      that the catalytically inactive D52S-Lz was as bactericidal as the Wt-Lz
      lysozyme. Heat treatment leading to enzyme inactivation had no effect on the
      bactericidal activity of either wild-type or the mutant D52S-Lz lysozyme. The
      binding affinity of D52S-Lz to the isolated peptidoglycan of S. aureus was
      unaffected. Our results provide the first demonstration of direct genetic
      evidence that the antimicrobial activity of lysozyme is operationally independent
      of its muramidase activity, and strongly suggest the antimicrobial action of
      lysozyme is due to structural factors.

PMID- 11591366
TI  - Pim-1 translocates sorting nexin 6/TRAF4-associated factor 2 from cytoplasm to
      nucleus.
AB  - Pim-1, an oncogene product of serine/threonine kinase, has been found to play
      roles in apoptosis induction/suppression, cell-cycle progression and
      transcriptional regulation by phosphorylating the target proteins involved in
      these processes. The target proteins phosphorylated by Pim-1, including p100,
      Cdc25A, PAP-1 and heterochromatin protein 1, have been identified. The precise
      functions of Pim-1, however, are still poorly understood. In this study, we
      identified tumor necrosis factor receptor-associated factor 4-associated factor
      2/sorting nexin 6 (TFAF2/SNX6) as a Pim-1-binding protein, and we found that
      TFAF2/SNX6 was phosphorylated and translocated from the cytoplasm to nucleus by
      Pim-1. This translocation of the protein was not affected by Pim-1-dependent
      phosphorylation. Since sorting nexins, including TFAF2/SNX6, have been reported
      to be located in the cytoplasm or membrane by association with several receptors
      of tyrosine- or serine/threonine-kinase, this is the first report of TFAF2/SNX6
      being located in the nucleus after binding to Pim-1.

PMID- 11591367
TI  - RXR beta isoforms in neuroblastoma cells and evidence for a novel 3'-end
      transcript.
AB  - RXR beta is predominantly involved in retinoid responses in neuroblastoma cells,
      in particular the N-type SH SY 5Y cells and the S-type SH S EP cells, both
      derivatives of a mixed phenotype neuroblastoma cell line. The aim of this study
      was to identify RXR beta isoforms expressed in neuroblastoma cells and to
      characterise a putative novel RXR beta transcript. RXR beta 1 and RXR beta 2 were
      expressed in these neuroblastoma cells. An isoform with an insertion into the
      ligand binding domain, RXR beta(SLSR) (referred to in previous studies as RXR
      beta 3), was expressed at a similar level to RXR beta. A novel RXR beta
      transcript was identified by RNase protection assays and was at least as abundant
      as the expected RXR beta transcript and expressed in other cell types. Evidence
      suggests that this novel transcript was transcribed from an internal promoter
      between exons 5 and 6, contained a retained intron (intron 6) and was
      alternatively spliced with and without the SLSR insertion. These data show that
      the pattern of RXR beta expression is complex. The relative abundance of the
      novel RXR beta transcript suggests that it may be an important aspect of RXR beta
      function or regulation in a range of cell types.

PMID- 11591368
TI  - GD3 glycosphingolipid contributes to Fas-mediated apoptosis via association with
      ezrin cytoskeletal protein.
AB  - Efficiency of Fas-mediated apoptosis of lymphoid cells is regulated, among other
      means, by a mechanism involving its association with ezrin, a cytoskeletal
      protein belonging to the 4.1 family of proteins. In the present work, we provide
      evidence for a further molecule that associates to ezrin in Fas-triggered
      apoptosis, the disialoganglioside GD3. In fact, as an early event, GD3
      redistributed in membrane-associated domains in uropods and co-localized with
      ezrin. Co-immunoprecipitation analyses confirmed this result, indicating a GD3
      ezrin association. Altogether, these results are suggestive for a role of GD3 in
      Fas/ezrin-mediated apoptosis, supporting the view that uropods contain a
      multimolecular signaling complex involved in Fas-mediated apoptosis.

PMID- 11591369
TI  - Interaction of bepridil with the cardiac troponin C/troponin I complex.
AB  - We have investigated the binding of bepridil to calcium-saturated cardiac
      troponin C in a cardiac troponin C/troponin I complex. Nuclear magnetic resonance
      spectroscopy and [(15)N,(2)H]cardiac troponin C permitted the mapping of bepridil
      induced amide proton chemical shifts. A single bepridil-binding site in the
      regulatory domain was found with an affinity constant of approximately 140
      microM(-1). In the presence of cardiac troponin I, bepridil binding to the C
      domain of cardiac troponin C was not detected. The pattern of bepridil-induced
      chemical shifts is consistent with stabilization of more open regulatory domain
      conformational states. A similar pattern of chemical shift perturbations was
      observed for interaction of the troponin I cardiac-specific amino-terminus with
      the cardiac troponin C regulatory domain. These results suggest that both
      bepridil and the cardiac-specific amino-terminus may mediate an increase in
      calcium affinity by interacting with and stabilizing open regulatory domain
      conformations. Chemical shift mapping suggests a possible role for inactive
      calcium-binding site I in the modulation of calcium affinity.

PMID- 11591370
TI  - Evidence for cell surface association between CXCR4 and ganglioside GM3 after
      gp120 binding in SupT1 lymphoblastoid cells.
AB  - CXCR4 (fusin) is a chemokine receptor which is involved as a coreceptor in gp120
      binding to the cell surface. In this study we provide evidence that binding of
      gp120 triggers CXCR4 recruitment to glycosphingolipid-enriched microdomains.
      Scanning confocal microscopy showed a nearly complete localization of CXCR4
      within GM3-enriched plasma membrane domains of SupT1 cells and
      coimmunoprecipitation experiments revealed that CXCR4 was immunoprecipitated by
      IgG anti-GM3 after gp120 pretreatment. These findings reveal that gp120 binding
      induces a strict association between CXCR4 and ganglioside GM3, supporting the
      view that GM3 and CXCR4 are components of a functional multimolecular complex
      critical for HIV-1 entry.

PMID- 11591372
TI  - Activation of ADAM 12 protease by copper.
AB  - Conversion of latent proteases to the active form occurs by various mechanisms
      characteristic for different protease families. Here we report that the
      disintegrin metalloprotease ADAM 12-S is activated by Cu(II). Copper activation
      is distinct from the cysteine switch component of latency: elimination of the
      ADAM 12 cysteine switch by a point mutation in the propeptide had no effect on
      copper activation, whereas mutation of an unpaired cysteine residue in the
      catalytic domain resulted in a mutant form of ADAM 12-S that was insensitive to
      copper. This suggests a multi-step activation mechanism for ADAM 12 involving
      both furin cleavage and copper binding.

PMID- 11591371
TI  - Two distinct isopentenyl diphosphate isomerases in cytosol and plastid are
      differentially induced by environmental stresses in tobacco.
AB  - Two distinct cDNA clones (IPI1 and IPI2) encoding IPI were isolated from
      Nicotiana tabacum. In situ expression of isopentenyl diphosphate isomerase-1
      (IPI1)- and IPI2-green fluorescent protein fusion constructs revealed that IPI1
      and IPI2 were localized in chloroplast and cytosol, respectively. The level of
      IPI1 mRNA was increased under high-salt and high-light stress conditions, while
      that of IPI2 mRNA was increased under high-salt and cold stress conditions. Both
      IPI transcripts were increased in an abscisic acid-independent manner. This is
      the first report of a cytosolic IPI. The results indicated that two distinct IPIs
      were differentially induced in response to stress.

PMID- 11591373
TI  - Ci-opsin1, a vertebrate-type opsin gene, expressed in the larval ocellus of the
      ascidian Ciona intestinalis.
AB  - A novel gene encoding visual pigment, Ci-opsin1, was identified in a primitive
      chordate, the ascidian, Ciona intestinalis. Molecular phylogenetic analysis and
      the exon-intron organization suggest that Ci-opsin1 is closely related to the
      retinal and pineal opsins of vertebrates. During embryogenesis, Ci-opsin1
      transcripts were first detected in part of the brain of mid tailbud embryos; its
      expression was confined to photoreceptor cells of the ocellus (eye spot) in the
      larval brain as development proceeded. These results suggest a common descent of
      the ascidian ocellus and the vertebrate eyes. The ocellus of ascidian larvae may
      represent an ancestral state of the vertebrate eye.

PMID- 11591374
TI  - Changes in mRNA expression profile underlie phenotypic adaptations in creatine
      kinase-deficient muscles.
AB  - We have studied the mechanisms that regulate the remodeling of the glycolytic,
      mitochondrial and structural network of muscles of creatine kinase M (M
      CK)/sarcomeric mitochondrial creatine kinase (ScCKmit) knockout mice by
      comparison of wild-type and mutant mRNA profiles on cDNA arrays. The magnitudes
      of changes in mRNA levels were most prominent in M-CK/ScCKmit (CK(-/-)) double
      mutants but did never exceed those of previously observed changes in protein
      level for any protein examined. In gastrocnemius of CK(-/-) mice we measured a
      2.5-fold increase in mRNA level for mitochondrial encoded cytochrome c oxidase
      (COX)-III which corresponds to the increase in protein content. The level of the
      nuclear encoded mRNAs for COX-IV, H(+)-ATP synthase-C, adenine nucleotide
      translocator-1 and insulin-regulatable glucose transporter-4 showed a 1.5-fold
      increase, also in agreement with protein data. In contrast, no concomitant up
      regulation in mRNA and protein content was detected for the mitochondrial
      inorganic phosphate-carrier, voltage-dependent anion channel and certain
      glycolytic enzymes. Our results reveal that regulation of transcript level plays
      an important role, but it is not the only principle involved in the remodeling of
      mitochondrial and cytosolic design of CK(-/-) muscles.

PMID- 11591375
TI  - Me and my genome.

PMID- 11591376
TI  - Down-regulation of N-myristoyl transferase expression in human T-cell line CEM by
      human immunodeficiency virus type-1 infection.
AB  - The present study focuses on the expression level of N-myristoyl transferase
      (NMT) in the course of human immunodeficiency virus type-1 (HIV-1) infection. HIV
      1 structural proteins were gradually expressed during the process of infection of
      the human T-cell line CEM, whereas the expression levels of NMT subsequently
      decreased under the same conditions. In addition, the chronically HIV-1-infected
      T-cell line CEM/LAV-1 exhibited low expression levels of NMT. We hypothesize that
      the decrease in the expression level of NMT due to HIV-1 infection may be related
      to the virus' strategy that leads to its persistent replication.

PMID- 11591377
TI  - The generation and characterisation of antagonist RNA aptamers to MCP-1.
AB  - Monocyte chemoattractant protein-1 (MCP-1) has been implicated as a powerful pro
      inflammatory mediator and may represent a potentially important, therapeutic
      opportunity for treatment of inflammatory disease and atherosclerosis. To further
      investigate the role of MCP-1 in inflammatory disorders we have isolated a series
      of RNA aptamers that bind specifically to mouse MCP-1. The highest affinity
      aptamers, designated ADR7 and ADR22, have been functionally characterised in
      vitro and in cell based assays. ADR7 and ADR22 have an affinity of 180 pM and 370
      pM respectively for mouse MCP-1, they can antagonise MCP-1 binding to heparin and
      specifically antagonise MCP-1 induced chemotaxis in a cell based assay. An
      interesting feature of ADR22 but not ADR7 is that it is capable of antagonising
      the function of human MCP-1, demonstrating the high level of specificity of these
      aptamers and that the aptamers recognise MCP-1 in different ways. The aptamers
      may be used as a tool to further investigate the role of MCP-1 in inflammatory
      disorders and may also have a role as a therapeutic agent.

PMID- 11591378
TI  - Mechanisms mediating the antiproliferative effects of nitric oxide in cultured
      human airway smooth muscle cells.
AB  - We have characterised the mechanisms involved in the antiproliferative effect of
      NO in human airway smooth muscle cells (HASMC). S-Nitroso-N-acetyl penicillamine,
      a nitric oxide donor, inhibited proliferation in both G(1) and S phases of the
      cell cycle. Additionally, experiments with 8-bromo-cGMP, haemoglobin, a NO
      scavenger and zaprinast, a cGMP-specific phosphodiesterase inhibitor, showed that
      both effects were NO-mediated. The G(1) phase inhibition was cGMP-dependent
      whereas the S phase inhibition was due to a cGMP-independent inhibition of
      ribonucleotide reductase. These results demonstrate that NO inhibits HASMC
      proliferation by cGMP-dependent and -independent mechanisms acting at distinct
      points in the cell cycle.

PMID- 11591379
TI  - Signaling pathways utilized by tumor necrosis factor receptor 1 in adipocytes to
      suppress differentiation.
AB  - Tumor necrosis factor-alpha (TNFalpha) has profound effects on cultured
      adipocytes, one of which is the inhibition of terminal differentiation. Previous
      studies in TNF receptor (TNFR)-deficient preadipocytes have demonstrated that the
      anti-adipogenic effect of both secreted and transmembrane TNFalpha is mediated
      solely by TNFR1. In this study, we performed a structure-function analysis of the
      intracellular domains of TNFR1 and investigated the signaling pathway(s) involved
      in TNFR1-mediated inhibition of adipocyte differentiation. Our results show that
      repression of adipogenesis required the juxtamembrane and death domains and was
      independent of the pathways involving nuclear factor kappaB and neutral
      sphingomyelinase.

PMID- 11591380
TI  - Export of Thermus thermophilus alkaline phosphatase via the twin-arginine
      translocation pathway in Escherichia coli.
AB  - The bacterial twin-arginine translocation (Tat) pathway is distinct from the Sec
      system by its remarkable capacity to export folded enzymes. To address the
      question whether the two systems are capable of translocating homologous enzymes
      catalyzing the same reaction, we cloned the tap gene encoding Thermus
      thermophilus alkaline phosphatase (Tap) and expressed it in Escherichia coli.
      Unlike the alkaline phosphatase of E. coli, which is translocated through the Sec
      system and then activated in the periplasm, Tap was exported exclusively via the
      Tat pathway and active Tap precursor was observed in the cytoplasm. These results
      demonstrate that two sequence and functional related enzymes are exported by
      distinct protein transport systems, which may play an integral role in the
      bacterial adaptation to their environment during the evolution.

PMID- 11591381
TI  - The chaperone activity of trigger factor is distinct from its isomerase activity
      during co-expression with adenylate kinase in Escherichia coli.
AB  - To investigate the molecular chaperone function of trigger factor (TF) and its
      relationship with isomerase activity in vivo, the assisted folding of adenylate
      kinase (AK) by TF in Escherichia coli was examined by measuring the amounts of
      soluble AK produced during co-expression. When the mutant of chicken AK, P17G, is
      expressed in plasmid pBVAK, 95% of the protein is found in inclusion bodies. Co
      expression of AK with TF was achieved using a plasmid pBVAT that allowed
      expression of TF and AK in the same plasmid under separate control. Co-expression
      with TF resulted in an increase in the amount of soluble AK, with a higher
      increase when TF was expressed at higher levels in the cell. Co-expression of AK
      with the two TF mutants, Y221G and F233Y, in which peptidyl-prolyl cis/trans
      isomerase activity was 1% of wild-type, gave the same results as wild-type TF.
      This provides in vivo evidence that the molecular chaperone activity of TF is
      distinct from its isomerase activity.

PMID- 11591382
TI  - Multimerization potential of the cytoplasmic domain of the human cytomegalovirus
      glycoprotein B.
AB  - In the present study the coding sequence of the cytoplasmic tail of the human
      cytomegalovirus glycoprotein B (gB) was expressed. The secondary structure of the
      purified recombinant protein was analyzed by circular dichroism, and the
      quaternary structure was investigated by gel permeation chromatography, and
      electron microscopy. Our data indicate that the cytoplasmic gB domain contains
      alpha-helix structures and assembles into tetramers, suggesting that the
      authentic gB may represent a homotetramer.

PMID- 11591383
TI  - Establishment of CHO cell lines expressing four N-methyl-D-aspartate receptor
      subtypes and characterization of a novel antagonist PPDC.
AB  - To develop an assay system that allows the N-methyl-D-aspartate (NMDA) receptor
      subtype-selective antagonistic potency of drugs, we have established Chinese
      hamster ovary cell lines expressing the four NMDA receptor subtypes
      (GluRepsilon1/zeta1-GluRepsilon4/zeta1) heat-indelibly. Using these clonal cells,
      we found that a novel antagonist, (1S,2R)-1-phenyl-2[(S)-1-aminopropyl]-N,N
      diethylcyclopropanecarboxamide, was less selective for the GluRepsilon1/zeta1:
      the IC(50) values for the GluRepsilon1/zeta1-GluRepsilon4/zeta1 were 41.7, 13.3,
      12.6 and 11.5 microM, respectively, while two well-known antagonists, DL-2-amino
      5-phosphonovaleric acid and ifenprodil, showed the known potency and selectivity
      for each subtype. Thus, the established clonal cells are of use in characterizing
      the pharmacological properties of drugs that act on NMDA receptors.

PMID- 11591384
TI  - The potato tuber transcriptome: analysis of 6077 expressed sequence tags.
AB  - This is the first report of the biosynthetic potential of a tuber storage organ
      investigated by expressed sequence tag sequencing. A cDNA library was generated
      from the mature tuber of field grown potato (Solanum tuberosum var. Kuras).
      Partial sequences obtained from 6077 clones were assembled into 828 clusters and
      1533 singletons. The average read length was 592 bp, and 2254 clones were full
      length. 5717 clones showed homology to genes from other organisms. Genes involved
      in protein synthesis, protein destination and cell defense predominated in tuber
      compared to stolon, shoot and leaf organs. 1063 clones were unique to tuber.
      Transcripts of starch metabolizing enzymes showed similar relative levels in
      tuber and stolon.

PMID- 11591385
TI  - A novel serum chitinase that is expressed in bovine liver.
AB  - Chitinases are ubiquitous chitin-fragmenting hydrolases. They are synthesized by
      a vast array of organisms, including those not composed of chitin. Here, we
      describe a novel serum chitinase (chitin-binding protein b04, CBPb04), which is
      expressed in bovine liver. Although CBPb04 is secreted as an endocrine chitinase,
      it shows higher homology with human gastrointestinal tract exocrine chitinase
      (AMCase) than with macrophage endocrine chitinase (human chitotriosidase). This
      suggests that cows have a specific defense against chitin-containing
      microorganisms. CBPb04 mRNA is expressed in hepatocytes. This is the first report
      of a hepatogenic mammalian chitinase.

PMID- 11591386
TI  - Reliable in vitro measurement of nitric oxide released from endothelial cells
      using low concentrations of the fluorescent probe 4,5-diaminofluorescein.
AB  - 4,5-Diaminofluorescein (DAF-2) and its membrane-permeable derivate DAF-2
      diacetate are fluorescent probes that have been developed to perform real-time
      biological detection of nitric oxide (NO). Their use for intracellular imaging,
      however, has recently been seriously questioned and data using DAF-2 for
      extracellular NO detection at low levels, as for example released from
      endothelial cells, are rare. Here we show that a reliable detection of low levels
      of NO in biological systems by DAF-2 is possible (a) by using low DAF-2
      concentrations (0.1 microM) and (b) by subtracting the DAF-2 auto-fluorescence
      from the measured total fluorescence. The described method allows easy real-time
      detection of endothelial NO formation.

PMID- 11591388
TI  - Toxicity of the bacterial luciferase substrate, n-decyl aldehyde, to
      Saccharomyces cerevisiae and Caenorhabditis elegans.
AB  - This study determined that the bacterial luciferase fusion gene (luxAB) was not a
      suitable in vivo gene reporter in the model eukaryotic organisms Saccharomyces
      cerevisiae and Caenorhabditis elegans. LuxAB expressing S. cerevisiae strains
      displayed distinctive rapid decays in luminescence upon addition of the bacterial
      luciferase substrate, n-decyl aldehyde, suggesting a toxic response. Growth
      studies and toxicity bioassays have subsequently confirmed, that the aldehyde
      substrate was toxic to both organisms at concentrations well tolerated by
      Escherichia coli. As the addition of aldehyde is an integral part of the
      bacterial luciferase activity assay, our results do not support the use of lux
      reporter genes for in vivo analyses in these model eukaryotic organisms.

PMID- 11591387
TI  - Induction of CHOP and apoptosis by nitric oxide in p53-deficient microglial
      cells.
AB  - Excessive nitric oxide (NO) has been implicated in neurotoxicity after stresses
      such as ischemia. NO toxicity is generally thought to be mediated by the DNA
      damage-p53 pathway or mitochondrial dysfunction. We investigated the mechanism of
      NO toxicity by using murine microglial MG5 cells established from p53-deficient
      mice. When MG5 cells were exposed to bacterial lipopolysaccharide plus interferon
      gamma, mRNA and protein for inducible NO synthase (iNOS) were markedly induced,
      and apoptosis occurred. Under these conditions, we found that mRNA and protein
      for CHOP/GADD153, a C/EBP family transcription factor which is involved in
      endoplasmic reticulum (ER) stress-induced apoptosis, are induced. iNOS mRNA was
      induced 2 h after treatment, whereas CHOP mRNA began to increase at 6 h with a
      time lag. CHOP mRNA was also induced by NO donors S-nitroso-N-acetyl-DL
      penicillamine (SNAP) or NOC18, or a peroxynitrite generator 3-(4-morpholinyl)
      sydnonimine hydrochloride (SIN-1). Bip/GRP78, an ER chaperone which is known to
      be induced by ER stress, was also induced by SNAP or SIN-1, indicating that NO
      causes ER stress. These results suggest that NO-induced apoptosis in MG5 cells
      occurs through the ER stress pathway involving CHOP, but is independent of p53.

PMID- 11591389
TI  - Membrane interactions and self-association of the TatA and TatB components of the
      twin-arginine translocation pathway.
AB  - The Escherichia coli Tat system mediates Sec-independent export of protein
      precursors bearing twin-arginine signal peptides. The essential Tat pathway
      components TatA, TatB and TatC are shown to be integral membrane proteins. Upon
      removal of the predicted N-terminal transmembrane helix TatA becomes a water
      soluble protein. In contrast the homologous TatB protein retains weak peripheral
      interactions with the cytoplasmic membrane when the analogous helix is deleted.
      Chemical crosslinking studies indicate that TatA forms at least homotrimers, and
      TatB minimally homodimers, in the native membrane environment. The presence of
      such homo-oligomeric interactions is supported by size exclusion chromatography.

PMID- 11591390
TI  - Functional characterization of the Bag7, Lrg1 and Rgd2 RhoGAP proteins from
      Saccharomyces cerevisiae.
AB  - Rho proteins are down-regulated in vivo by specific GTPase activating proteins
      (RhoGAP). We have functionally studied three Saccharomyces cerevisiae putative
      RhoGAP. By first identifying Rho partners with a systematic two-hybrid approach
      and then using an in vitro assay, we have demonstrated that the Bag7 protein
      stimulated the GTPase activity of the Rho1 protein, Lrg1p acted on the Cdc42 and
      Rho2 GTPases and we showed that Rgd2p has a GAP activity on both Cdc42p and
      Rho5p. In addition, we brought the first evidence for the existence of a sixth
      functional Rho in yeast, the Cdc42/Rac-like GTPase Rho5.

PMID- 11591391
TI  - Inhibition of myogenesis enables adipogenic trans-differentiation in the C2C12
      myogenic cell line.
AB  - C2C12 cells are a well-established model system for studying myogenesis. We
      examined whether inhibiting the process of myogenesis via expression of dominant
      negative (DN) mitogen-activated protein kinase kinase-3 (MKK3) facilitated the
      trans-differentiation of these cells into adipocytes. Cells expressing DN MKK3
      respond to rosiglitazone, resulting in adipocyte formation. The effects of
      rosiglitazone appear to be potentiated through peroxisome proliferator activating
      receptor-gamma. This trans-differentiation is inhibited by the use of the
      phosphoinositide-3 (PI3) kinase inhibitor, LY294002. These results indicate that
      preventing myogenesis through expression of DN MKK3 facilitates adipocytic trans
      differentiation, and involves PI3 kinase signalling.

PMID- 11591392
TI  - Localization of neutral ceramidase in caveolin-enriched light membranes of murine
      endothelial cells.
AB  - Sphingomyelinase (SMase) and ceramidase (CDase) activities participate in
      sphingomyelin (SM) metabolism and have a role in the signal transduction of a
      variety of ligands. In this study evidence is presented that caveolin-enriched
      light membranes (CELMs) of murine endothelial cells, characterized by high SM,
      ceramide (Cer) and cholesterol content, bear acid and neutral SMase as well as
      neutral CDase activities. Localization of neutral CDase in CELMs was confirmed by
      Western analysis. Notably, cell treatment with cyclodextrin, which depleted cell
      cholesterol, did not affect acid or neutral SMase activities but significantly
      enhanced neutral CDase activity in CELMs, indicating a negative role for
      cholesterol in CDase regulation. These findings suggest that neutral CDase is
      implicated, together with SMase activities, in the control of caveolar Cer
      content that may be critical for caveola dynamics.

PMID- 11591393
TI  - Neuroimaging of aging and estrogen effects on central nervous system physiology.
AB  - OBJECTIVE: To review the literature on neuroimaging studies focusing on gender
      differences in the aging process and on the effects of postmenopausal estrogen
      use on the brain. DESIGN: Pertinent studies were identified through a computer
      MEDLINE search. References of selected articles were hand-searched for additional
      citations. CONCLUSION(S): The current literature suggests that estrogen
      replacement may decrease brain white matter lesions, increase cerebral blood
      flow, alter regional brain activation patterns during cognitive processing, and
      have modulatory effects on various neurotransmitter systems. Overall, this points
      to a functional plasticity in higher order brain processing that can be altered
      by gonadal steroids.

PMID- 11591394
TI  - Human embryonic stem cells.

PMID- 11591395
TI  - Does ovarian surgery for endometriomas impair the ovarian response to
      gonadotropin?
AB  - OBJECTIVE: To evaluate the ovarian response to stimulation conducted for IVF
      treatment in women who have undergone conservative surgery for endometriomas.
      DESIGN: Retrospective study with prospective selection of participants and
      controls. SETTING: University infertility clinic. PATIENT(S): A series of 374
      women who underwent in vitro fertilization (IVF). The study group consisted of 85
      patients with ovarian endometriomas who had undergone laparoscopic surgery in an
      attempt to become pregnant, but had failed within a year of surgery. The control
      group consisted of 289 patients with tubal factor infertility. INTERVENTION(S):
      IVF-embryo transfer procedures. MAIN OUTCOME MEASURE(S): Stimulation parameters,
      fertilization, implantation, and pregnancy rates were analyzed in both groups.
      RESULT(S): There was no significant difference between the two groups in
      stimulation parameters or IVF outcome. CONCLUSION(S): A total of 820 cycles were
      analyzed. A similar IVF-ET outcome was observed in patients with endometriosis
      after ablation of endometriomas compared to women with tubal factors. In
      conclusion, endometrioma surgery by internal wall vaporization does not impair
      IVF outcome. The clinical pregnancy rate was respectively 37.4% and 34.6% in the
      endometriosis group and the control group.

PMID- 11591396
TI  - Reproductive outcome in patients with diminished ovarian reserve.
AB  - OBJECTIVE: To compare reproductive outcome between women with normal ovarian
      reserve and women with abnormal ovarian reserve. DESIGN: Retrospective. SETTING:
      Tertiary care center. PATIENT(S): Nine thousand eight hundred and two patients
      who had basal follicle-stimulating hormone (FSH) concentrations measured as part
      of an infertility evaluation. INTERVENTION(S): Monitoring of early pregnancy.
      MAIN OUTCOME MEASURE(S): Pregnancy loss rates, live birth rates. RESULT(S): Of
      1,034 patients with diminished ovarian reserve (DOR) (FSH > or =14.2 IU/L), 28
      (2.7%) conceived. Twenty of these pregnancies (20/28; 71.4%) were lost in the
      first trimester. Pregnancy loss rates in women with DOR were 57.1% in women <35
      years old, 63.5% in women 35-40 years old, and 90.0% in women >40 years old.
      These rates of pregnancy loss were significantly higher compared to age-matched
      patients with normal ovarian reserve. CONCLUSIONS(S): Women with DOR have
      exceedingly high rates of pregnancy loss, regardless of age. Women with
      diminished ovarian reserve should be counseled that, in addition to a low
      probability of conception, live birth rates are poor.

PMID- 11591397
TI  - Controlled ovarian hyperstimulation does not adversely affect endometrial
      receptivity in in vitro fertilization cycles.
AB  - OBJECTIVE: To determine whether exposure of developing endometrium to
      supraphysiologic E2 levels during controlled ovarian hyperstimulation (COH) in
      IVF cycles inhibits endometrial receptivity. DESIGN: Retrospective analysis of
      IVF-ET and ovum donation data. SETTING: Tertiary-care teaching hospital.
      PATIENT(S): Four hundred ten patients <33 years of age undergoing IVF-ET and 181
      anonymous ovum donors (<33 years of age) and their associated ovum recipients.
      MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and delivery rates. RESULT(S):
      Ovarian response to COH (duration of stimulation, peak E2 level, area under the
      curve for E2 exposure, and number of oocytes retrieved) was similar for IVF-ET
      patients and ovum donors. Donors were younger than IVF-ET patients (mean age,
      27.5 +/- 0.2 years vs. 30.4 +/- 0.1 years). A similar number of embryos with
      similar number of blastomeres were transferred in IVF-ET patients and ovum
      recipients. The fragmentation rate at time of transfer differed slightly between
      groups (5.2 +/- 0.2% vs. 4.3 +/- 0.3%). Implantation, pregnancy, and delivery
      rates did not differ between IVF-ET patients and recipients of donor oocytes.
      CONCLUSION(S): Exposure of the developing endometrium to controlled ovarian
      hyperstimulation during IVF cycles does not inhibit embryo implantation or affect
      pregnancy and delivery rates.

PMID- 11591398
TI  - A prospective study of stress among women undergoing in vitro fertilization or
      gamete intrafallopian transfer.
AB  - OBJECTIVE: To evaluate whether baseline or procedural stress during in vitro
      fertilization (IVF) or gamete intrafallopian transfer (GIFT) affects pregnancy or
      live birth delivery rates. DESIGN: Prospective study. SETTING: Seven clinics in
      Southern California between 1993 and 1998. PATIENT(S): One hundred and fifty-one
      women completed two questionnaires. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): The number of oocytes aspirated and fertilized, the number of embryos
      transferred, the achievement of a pregnancy, live birth delivery, and infant
      outcomes. RESULT(S): Positive-affect negative-affect score at baseline negatively
      influenced the number of oocytes retrieved and embryos transferred. A higher
      expectation of pregnancy was associated with greater numbers of oocytes
      fertilized and embryos transferred. At baseline, the risk of no live birth was
      93% lower for women who had the highest positive-affect score compared to those
      with the lowest score. Furthermore, the score on the Infertility Reaction Scale
      was related to negative outcomes in live birth delivery, infant birth weight, and
      multiple births. During the time of the procedure, the PANAS and Bipolar Profile
      of Moods States results were related to the number of oocytes fertilized and
      embryos transferred; stress did not affect pregnancy or delivery. CONCLUSION(S):
      Baseline (acute and chronic) stress affected biologic end points (i.e., number of
      oocytes retrieved and fertilized), as well as pregnancy, live birth delivery,
      birth weight, and multiple gestations, whereas (procedural) stress only
      influenced biologic end points.

PMID- 11591399
TI  - Sex ratio and birth weights of infants born as a result of blastocyst transfers
      compared with early cleavage stage embryo transfers.
AB  - OBJECTIVE: To analyze the birth weights and sex ratio of infants born as a result
      of blastocyst transfer and compare them with data resulting from the transfer of
      early-cleavage stage embryos. DESIGN: Retrospective analysis. SETTING: Monash IVF
      (private in vitro fertilization clinic). PATIENTS(S): One hundred twenty-five
      infertile patients who became pregnant after IVF procedures involving blastocyst
      transfer. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sex ratio and birth
      weights of infants born after blastocyst transfer. RESULT(S): The sex ratio of
      129.6 for infants born after blastocyst transfer was not significantly different
      from the sex ratio calculated from data compiled by NPSU for births resulting
      from early cleavage stage embryo transfers at Monash IVF (100.6) and all other
      assisted conception units in Australia and New Zealand (97.9). No differences
      were observed in the combined mean birth weight of male and female infants born
      as a result of blastocyst transfers and early-cleavage stage embryo transfers.
      CONCLUSION(S): There is no evidence of abnormal fetal growth or a shift in the
      sex ratio for infants born as a result of blastocyst transfer when compared with
      the case of births resulting from early cleavage stage embryo transfers within
      our unit or all other assisted conception units in Australia and New Zealand.

PMID- 11591400
TI  - Anti-annexin V antibodies in patients with early pregnancy loss or implantation
      failures.
AB  - OBJECTIVE: To describe the prevalence of annexin V antibodies (aANX) in women
      with early recurrent pregnancy losses (RPLs) or recurrent IVF-ET failure. DESIGN:
      Retrospective data analysis. SETTING: Tokai University Hospital, Kanagawa, Japan.
      PATIENT(S): Two hundred thirty-eight patients with RPLs, 48 patients with
      recurrent IVF-ET failure and 179 nonpregnant and 120 pregnant control group
      women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): ELISA was used to measure
      autoantibodies to annexin V. RESULT(S): An ELISA system developed for aANX
      revealed a dose-dependent relationship between annexin V and aANX. The
      positive/negative cutoff was set at 7 multiples of the median based on the 99th
      percentile of normal nonpregnant control group patients. Patients with RPLs
      (5.5%) or recurrent IVF-ET failure (8.3%) had a significantly increased incidence
      of aANX (IgG) compared with normal nonpregnant (1.1%) or pregnant control group
      women (0), whereas the prevalence of aANX between both patient groups or between
      both control groups was not statistically different. Specificity was confirmed by
      absorption studies using annexin V and by immunoblots. CONCLUSION(S): Our data
      show that aANX are associated with both RPLs and IVF-ET failure. We propose that
      anti-annexin V antibodies should be considered a risk factor for these
      reproductive failures.

PMID- 11591401
TI  - Is interleukin-3 important in antiphospholipid antibody-mediated pregnancy
      failure?
AB  - OBJECTIVE: To investigate the effect of interleukin-3 (IL-3) on trophoblast
      proliferation and expression of beta2-glycoprotein I. DESIGN: In vitro cell
      culture using primary trophoblasts and the cell lines Jeg-3, Jar, and BeWo.
      SETTING: Department of Obstetrics and Gynaecology, University of Auckland.
      PATIENT(S): Women with normal pregnancies. INTERVENTION(S): Increasing amounts of
      IL-3 were added to cultures of primary human trophoblasts, cell lines, or cells
      treated with a proliferation inhibiting antiphospholipid-like antibody. RNA was
      extracted from primary human trophoblasts or cell lines. MAIN OUTCOME MEASURE(S):
      We examined basal and IL-3-stimulated cellular proliferation by [3H] thymidine
      incorporation assay and secretion of beta2-glycoprotein I into culture medium by
      semiquantitative immunoblot analysis. Reverse transcriptase-polymerase chain
      reaction analysis was used to demonstrate the presence of IL-3 receptor
      transcripts. RESULT(S): The IL-3 treatment did not induce proliferation of highly
      purified primary trophoblast cultures or cell lines but did induce proliferation
      of contaminating CD45+ cells in trophoblast cultures. The IL-3 did not overcome
      the antiproliferative effect of an antiphospholipid-like monoclonal antibody on
      trophoblast. Secretion of beta2-glycoprotein I by trophoblast cultures was time
      dependent but unaltered by IL-3 treatment. CONCLUSION(S): Our results question
      the proposed importance of IL-3 in antiphospholipid antibody-mediated fetal
      death.

PMID- 11591402
TI  - Maternal serum levels of tumor necrosis factor-alpha and interleukin-2 receptor
      in threatened abortion: a comparison with normal and pathologic pregnancies.
AB  - OBJECTIVE: We evaluated tumor necrosis factor-alpha (TNF-alpha) and interleukin-2
      (IL-2) receptor levels in patients with threatened abortion and compared the
      levels with normal and pathologic pregnancies. DESIGN: A prospective,
      nonrandomized, case-control study. SETTING: Academic research setting.
      PATIENT(S): Twenty-two patients with threatened abortion, 18 patients with
      pathologic pregnancies, 20 healthy pregnant women, and 20 nonpregnant women.
      INTERVENTION(S): Maternal serum TNF-alpha and IL-2 receptor levels were measured
      with a solid-phase, two-site chemiluminescent enzyme immunometric assay method.
      MAIN OUTCOME MEASURE(S): TNF-alpha and IL-2 receptor levels. RESULT(S): The mean
      +/- SEM maternal serum IL-2 receptor level for patients with threatened abortion
      was 481.3 +/- 35.7 U/mL, compared with 426.5 +/- 22.4 U/mL in the normal pregnant
      group. There was no statistically significant difference in the mean +/- SEM
      serum TNF-alpha level between the patients with threatened abortion and those
      with normal pregnancies (16.1 +/- 2.7 pg/mL vs. 10.9 +/- 0.8 pg/mL). The mean +/-
      SEM maternal serum IL-2 receptor level was significantly higher in patients with
      pathologic pregnancies than in those with normal pregnancies (506.2 +/- 27.6 U/mL
      vs. 426.5 +/- 22.4 U/mL). The mean +/- SEM maternal serum TNF-alpha level was
      significantly higher in patients with pathologic pregnancies than in those with
      threatened abortion (39.2 +/- 9.5 pg/mL vs. 16.1 +/- 2.7 pg/mL) and normal
      pregnancies (39.2 +/- 9.5 pg/mL vs. 10.9 +/- 0.8 pg/mL). CONCLUSION(S): In
      comparison with normal pregnancies, maternal serum IL-2 receptor and TNF-alpha
      levels were not significantly increased in patients with threatened abortion with
      good outcome.

PMID- 11591403
TI  - Immunohistochemical analysis of the role of angiogenic status in the vasculature
      of peritoneal endometriosis.
AB  - OBJECTIVE: To investigate the angiogenic status of the vasculature in peritoneal
      endometriosis based on macroscopic appearance. DESIGN: Prospective study.
      SETTING: University hospital. PATIENT(S): Patients with peritoneal endometriosis.
      INTERVENTION(S): During laparoscopy, 25 samples of predominantly red peritoneal
      lesions and 27 samples of predominantly black peritoneal lesions were collected
      from a total of 31 patients with endometriosis. Eutopic endometrium from 25
      patients with endometriosis was collected by curettage during laparoscopy or just
      after surgery. MAIN OUTCOME MEASURE(S): A proliferating endothelial cell index
      (PCI) was determined by calculating the percentage of microvessels that contained
      proliferating endothelial cells. A vessel maturation index (VMI) was determined
      by calculating the percentage of microvessels showing colocalization of CD34- and
      alpha-SMA-positive staining. RESULT(S): Peritoneal endometriotic tissues had
      extremely low or null PCI. The VMI of red peritoneal lesions was significantly
      lower than that of black ones. Vessel maturation index of red lesions was higher
      that that of proliferative eutopic endometrium and similar to that of secretory
      eutopic endometrium. CONCLUSION(S): Compared with the case of black peritoneal
      lesions, red lesions had a much higher fraction of immature vessels.

PMID- 11591404
TI  - High omega-3:omega-6 fatty acid ratios in culture medium reduce endometrial-cell
      survival in combined endometrial gland and stromal cell cultures from women with
      and without endometriosis.
AB  - OBJECTIVE: To study the effects of omega-3 and omega-6 polyunsaturated fatty acid
      (PUFA) on in vitro proliferation of endometrial cells and their production of the
      cytokine interleukin-8 (IL-8). DESIGN: In vitro study. SETTING: Obstetrics and
      gynecology department, University of Aberdeen. PATIENT(S): Women attending an
      infertility clinic. INTERVENTION(S): In vitro cell cultures using culture mediums
      supplemented with normal and high ratios of omega-3 PUFA and omega-6 PUFA. MAIN
      OUTCOME MEASURE(S): In vitro survival and production of IL-8 by dispersed
      endometrial cells. RESULT(S): In vitro survival of endometrial cells from women
      with and without endometriosis was significantly reduced in the presence of high
      omega-3:omega-6 PUFA ratios compared with cells incubated in the absence of fatty
      acids, in balanced omega-3:omega-6 PUFA ratios, and in high omega-6:omega-3 PUFA
      ratios. Endometrial cells from women with endometriosis secreted higher
      concentrations of IL-8, especially in the presence of high omega-3:omega-6 PUFA
      ratios. CONCLUSION(S): omega-3 PUFA may have a suppressive effect on the in vitro
      survival of endometrial cells and omega-3 PUFA be useful in the management of
      endometriosis by reducing the inflammatory response and modulating cytokine
      function.

PMID- 11591405
TI  - Early follicular phase hormone levels in relation to patterns of alcohol,
      tobacco, and coffee use.
AB  - OBJECTIVE: To examine the effects of alcohol, caffeine, and tobacco use on early
      follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG). DESIGN:
      Cross-sectional study. SETTING: Academic medical center. PATIENT(S): Four hundred
      ninety-eight women selected from the general population, ages 36-45, who were not
      currently pregnant, breast feeding, or using exogenous hormones. INTERVENTION(S):
      A general questionnaire assessing demography, anthropometry, and smoking habits
      and a standardized dietary questionnaire assessing food and beverage frequencies,
      including sources of alcohol and caffeine. MAIN OUTCOME MEASURE(S): FSH, LH, E2,
      and SHBG levels measured during the early follicular phase of the menstrual
      cycle. RESULT(S): Significant associations observed in a univariate analysis
      included age > or =40 and current smoking associated with higher FSH; higher body
      mass index (BMI) associated with lower SHBG levels; and daily alcohol use,
      cholesterol consumption greater than the median, and coffee use >1 cup/d
      associated with higher E2 levels. In a multivariate model, total caffeine use was
      significantly associated with E2 levels after adjustment for age, BMI, total
      calories, current smoking, alcohol, cholesterol consumption, and day of sampling.
      Early follicular phase E2 increased from 28.2 pg/mL for women consuming < or =100
      mg of caffeine to 45.2 pg/mL for women consuming > or =500 mg of caffeine per
      day, about a 70% increase. CONCLUSION(S): Coffee consumption and total caffeine
      use may increase early follicular phase E2 levels independent of related habits
      of alcohol or tobacco use.

PMID- 11591406
TI  - Influence of insulin and testosterone on adrenocortical steroidogenesis in vitro:
      preliminary studies.
AB  - OBJECTIVE: The mechanisms underlying the adrenal androgen (AA) excess of
      polycystic ovary syndrome (PCOS) remain unclear, although it is possible that the
      adrenocortical dysfunction may be a response to other, extraadrenal factors.
      Consistent with the pathophysiology of PCOS and with in vivo data in normal and
      PCOS women, we have hypothesized that insulin inhibits and that T stimulates AA
      secretion in vitro. DESIGN: In vitro experimental study. SETTING: University
      medical center. PATIENT(S): Normal human adrenals (n = 4 women, ages 25-57 years)
      were obtained with consent at the time of organ donation. INTERVENTION(S): Fresh
      adrenal tissue minces were incubated in serum-free medium with 10-microM
      pregnenolone substrate and 1-microM ACTH-(1-24). Challenge doses of 0.2, 1, 5,
      20, and 100 nM of insulin and 1, 10, 100, 1,000, and 10,000 nM of T were added,
      and the media were sampled after 8 hours of incubation at 37 degrees C, 4% CO2.
      Dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), and cortisol (F) were
      measured by radioimmunoassay (significant effects compared with the case of zero
      dose control). MAIN OUTCOME MEASURE(S): The production of DHEA, DHEAS, and F in
      the media of the adrenal minces was compared between different subjects and at
      different concentrations of T and insulin. RESULT(S): Analysis of the combined
      data from all donors indicated that insulin stimulated DHEAS and suppressed DHEA
      production but had no consistent effect on F. Similar analyses of the combined
      data indicated that T had no significant predictable effect on the production of
      DHEAS, DHEA, or F. When examining donor data individually, insulin and T did
      elicit significant increases and/or decreases in steroid production within
      subjects, although no consistent trends were observed. CONCLUSION(S): On the
      basis of these data, it is clear that extra-adrenal factors such as insulin and T
      have some adrenal regulatory capacity. In general, insulin stimulated DHEAS and
      decreased DHEA production, suggesting that it increases adrenocortical
      sulfotransferase activity. However, although in the individual subjects studied,
      both insulin and T frequently altered the production of DHEAS, DHEA or F, these
      effects did not appear to be uniform or consistent from subject to subject.
      Expanded studies are required to confirm these results.

PMID- 11591407
TI  - Uterorelaxing effects of vaginal progesterone: comparison of two methodologies
      for assessing uterine contraction frequency on ultrasound scans.
AB  - OBJECTIVE: To assess the changes in uterine contractility induced by increasing
      doses of P administered to estrogenized women and to compare two methodologies
      for assessing uterine contraction frequency from ultrasound scans. DESIGN:
      Prospective double-blind parallel study. SETTING: Academic tertiary center.
      PATIENT(S): Infertile women aged 21-39 years with premature ovarian failure.
      INTERVENTION(S): P support set to duplicate the luteal phase was provided every 2
      days by application of 1.125 g of Crinone 4% and 8% or 2.25 g of Crinone 8%,
      containing 45, 90, and 180 mg of P per application, respectively. MAIN OUTCOME
      MEASURE(S): Changes in uterine contraction frequency following exposure to three
      doses of vaginal P on ultrasound scans analyzed by visualizing accelerated image
      sequences and using a previously described three-dimensional (3D)-derived
      approach. RESULT(S): A decrease in uterine contraction frequency reached
      statistical significance on the third day of exposure to P without differences
      between the three dose groups. The two methods for measuring uterine contraction
      frequency on ultrasound scans were equivalent. CONCLUSION(S): At all three doses
      studied, the vaginal P gel Crinone administered to estrogenized women induced a
      profound decrease in uterine contraction frequency that duplicated the changes in
      contractility described in the luteal phase of the menstrual cycle. Analyzing
      uterine contraction frequency on accelerated image sequences is as effective as
      our more complex approach based on identifying contractions on time mode graphs
      electronically reconstructed using 3D-software.

PMID- 11591408
TI  - Inconsistent effects of the proline12 --> alanine variant of the peroxisome
      proliferator-activated receptor-gamma2 gene on body mass index in children and
      adolescent girls.
AB  - OBJECTIVE: To ascertain whether variation in peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma), a nuclear ligand-dependent transcription factor
      affecting both adipocyte differentiation and insulin sensitivity, influences body
      mass index (BMI). DESIGN: Association study. SETTING: Academic research
      environment. PATIENT(S): Children with premature pubic hair and adolescent girls
      with hyperandrogenism. INTERVENTION(S): Assay for P12A and P115Q variants and
      measure BMI. MAIN OUTCOME MEASURE(S): BMI and PPAR-gamma genotypes. RESULT(S):
      Fourteen subjects were heterozygous for P12A; two were homozygous. None carried
      the P115Q allele. No significant differences in BMI or basal androstenedione
      concentrations between P12 carriers and noncarriers were found. Thirty-nine
      subjects had BMI values at two time points; mean BMI was significantly greater in
      the P12A carriers at time point 2. Those P12A carriers obese at time point 1
      became more obese; lean mutation carriers tended to remain lean. Annual rate of
      increase in BMI was significantly greater in the P12A carriers than the
      noncarriers. CONCLUSION(S): Our findings suggest that P12A may be a genetic
      marker indicating risk for obesity persisting into adolescence. Future studies
      are needed to determine whether the divergent effects of P12A persist into
      adulthood, to elucidate the mechanism of this effect, and to replicate our
      findings in other populations.

PMID- 11591410
TI  - Vaginal-cervical epithelial permeability decreases after menopause.
AB  - OBJECTIVE: To determine the effects of menopause (aging and E) on vaginal
      cervical epithelial paracellular permeability. DESIGN: Experimental, basic
      clinical research. SETTING: Academic research environment. PATIENT(S):
      Premenopausal, perimenopausal, and postmenopausal women, aged 35-65 years.
      INTERVENTION(S): Primary to tertiary cultures of normal human ectocervical
      epithelial cells on filters. Cells were outgrown from surgically discarded
      ectocervical minces. MAIN OUTCOME MEASURE(S): Changes in paracellular
      permeability were determined as changes in transepithelial electrical conductance
      and pyranine permeability. RESULT(S): [1] Levels of transepithelial electrical
      conductance and pyranine permeability decreased as women's age advanced. [2]
      Removal of E from the culture medium decreased paracellular permeability.
      Treatment of cells in vitro with 10 nmol/L 17beta-E2 increased transepithelial
      electrical conductance and pyranine permeability, but the effects were additive
      to the age-related decrease in permeability. [3] Coadministration of 100 nmol/L
      tamoxifen blocked the E increase in paracellular permeability in cells of both
      premenopausal and postmenopausal women. CONCLUSION(S): [1] Aging and E deficiency
      decrease independently vaginal-cervical epithelial paracellular permeability. [2]
      The E increase in vaginal-cervical epithelial paracellular permeability in cells
      of postmenopausal women is mediated by the E receptor. [3] The E increase in
      vaginal-cervical epithelial paracellular permeability in cells of postmenopausal
      women is masked by age-related increase in the tight junctional resistance,
      leading to overall decrease in paracellular permeability.

PMID- 11591409
TI  - A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis
      in women with progestin-negative functional hypothalamic amenorrhea.
AB  - OBJECTIVE: To longitudinally evaluate disturbances of the hypothalamic-pituitary
      adrenal (HPA) axis in women with secondary progestin-negative hypothalamic
      amenorrhea. DESIGN: Retrospective cohort study. SETTING: Yokohama City
      University, Yokohama, Japan. PATIENT(S): Twenty-four women with progestin
      negative hypothalamic amenorrhea. INTERVENTION(S): Administration of human
      corticotropin-releasing hormone (hCRH) and treatment with a combination of
      estrogen and progesterone. MAIN OUTCOME MEASURE(S): Plasma cortisol and ACTH
      concentrations and period required for recovery from amenorrhea. RESULT(S):
      Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the
      percent maximum increment (%Cmax) of ACTH were significantly lower in the
      amenorrheic patients compared with the control group patients. The basal cortisol
      was significantly higher, and the %Cmax of cortisol was significantly lower. In
      the 16 patients who recovered from amenorrhea, there was a significant positive
      correlation (Y = 1.93X-10.8, r = 0.629) between the basal cortisol concentrations
      (X) and the period for recovery (Y). The serum E2 gradually increased before
      recovery, and this E2 increase was preceded by changes in the plasma cortisol
      concentration and the %Cmax values of cortisol and ACTH. CONCLUSION(S): The CRH
      test might be useful for evaluating the roles of stress and for estimating the
      period required for recovery in hypothalamic amenorrhea.

PMID- 11591411
TI  - Cyclic changes in expression of mRNA of vascular endothelial growth factor, its
      receptors Flt-1 and KDR/Flk-1, and Ets-1 in human corpora lutea.
AB  - OBJECTIVE: To evaluate the expression of mRNA of vascular endothelial growth
      factor (VEGF), its receptors Flt-1 and KDR/Flk-1, and Ets-1 in human corpora
      lutea. DESIGN: Prospective laboratory study. SETTING: University hospital in
      Japan. PATIENT(S): Women with regular menstrual cycles who underwent
      hysterectomy. INTERVENTION(S): Fifteen corpora lutea were obtained during
      hysterectomy (5 in the early luteal phase, 5 in the mid-luteal phase, and 5 in
      the late luteal phase). MAIN OUTCOME MEASURE(S): Expression of VEGF, Flt-1,
      KDR/Flk-1, and Ets-1 in human corpora lutea on northern blot analysis or
      immunohistochemistry. RESULT(S): Human corpora lutea in early luteal phase and
      mid-luteal phase had high VEGF mRNA expression. Expression of VEGF mRNA was
      significantly reduced in the late luteal phase. Immunohistochemistry showed that
      VEGF protein was expressed mainly in granulosa lutein cells and faintly in thecal
      lutein cells. Staining of VEGF protein was decreased in human corpora lutea in
      the late luteal phase. Expression of Flt-1 and KDR/Flk-1 mRNA was increased in
      the early luteal phase and mid-luteal phase and decreased in the late luteal
      phase. Immunohistochemistry showed that Flt-1 and KDR/Flk-1 proteins were
      expressed mainly in granulosa lutein cells and faintly in thecal lutein cells and
      endothelial cells in the early luteal phase and mid-luteal phase; their protein
      staining was reduced in the late luteal phase. Expression of Ets-1 mRNA changed
      similarly to VEGF and its receptor mRNA in human corpora lutea during the luteal
      phase. CONCLUSION(S): Levels of mRNA of VEGF and its receptors Flt-1 and KDR/Flk
      1 in human luteal cells may be related to luteal function.

PMID- 11591412
TI  - Relationship between expansion of the CAG repeat in exon 1 of the androgen
      receptor gene and idiopathic male infertility.
AB  - OBJECTIVE: To determine whether expansion of CAG repeats in exon 1 of the
      androgen receptor is correlated with impaired spermatogenesis in patients with
      male idiopathic infertility. DESIGN: A retrospective study. SETTING: Medical
      school in Besancon, France. PARTICIPANT(S): Thirty-seven infertile patients with
      azoospermia or oligospermia and 50 fertile controls. INTERVENTION(S): History,
      physical, hormonal assays, semen analysis, and collection of blood samples in
      order to study the androgen receptor's gene. MAIN OUTCOME MEASURE(S): Blood
      samples were collected from each infertile patient and control. The length of the
      CAG repeat segment was evaluated by using polymerase chain reaction (PCR)
      electrophoresis in exon 1 and PCR single-strand conformation polymorphism in
      exons 2-8. RESULT(S): The mean length of the CAG repeats was significantly
      different between infertile and fertile patients (23.91 +/- 0.5 vs. 22.20 +/-
      0.4). No mutation was detected in exons 2-8 of the androgen receptor gene in
      infertile patients. CONCLUSION(S): Expansion of the CAG repeat segment of the
      androgen receptor is correlated with male idiopathic infertility. The number of
      CAG repeats may therefore have a modulatory effect on normal androgen receptor
      function.

PMID- 11591413
TI  - Endometrial osteopontin, a ligand of beta3-integrin, is maximally expressed
      around the time of the "implantation window".
AB  - OBJECTIVE: To analyze endometrial mRNA and protein expression of osteopontin and
      its receptor, beta3-integrin, throughout the menstrual cycle. DESIGN: Study by
      immunohistochemistry, RNase protection assay, and ELISA. SETTING: Academic
      research unit. PATIENT(S): Forty-five regularly cycling women without endometrial
      pathology. INTERVENTION(S): Expression of endometrial osteopontin and beta3
      integrin mRNA was analyzed by RNase protection assay in endometrium, endometrial
      epithelial cells, stromal cells, and endometrial leukocytes (CD45) and by
      immunohistochemistry in frozen sections of endometrium throughout the menstrual
      cycle. Concentration of osteopontin was studied in uterine secretions by ELISA.
      MAIN OUTCOME MEASURE(S): mRNA and protein expression of osteopontin and beta3
      integrin. RESULT(S): Osteopontin mRNA and protein was weakly expressed in the
      proliferative phase and maximally expressed in the mid to late secretory phases
      in endometrium, endometrial epithelial cells, and endometrial leukocytes and in
      uterine secretions. Beta3-integrin mRNA and protein were expressed in stromal
      cells throughout the menstrual cycle and were maximally expressed in epithelial
      cells in the mid to late secretory phases. CONCLUSION(S): Expression of
      osteopontin and its receptor, beta3-integrin, in human endometrial glands and
      osteopontin secretion into the uterine cavity around the time of the
      "implantation window" suggest a role for these proteins in endometrial function
      and implantation.

PMID- 11591415
TI  - Effect of gonadotropin-releasing hormone agonists on monocyte chemotactic protein
      1 production and macrophage infiltration in leiomyomatous uterus.
AB  - OBJECTIVE: The level of monocyte chemotactic protein-1 (MCP-1), a potent
      chemoattractant for monocytes, is fivefold higher in myometrium than in
      leiomyoma. We have previously shown that myometrium from women using GnRH
      agonists (GnRH-a) express the highest levels of MCP-1, which has
      antiproliferative effects on leiomyoma cells. We hypothesized that MCP-1 may have
      a direct paracrine effect in leiomyomatous uterus rather than acting by way of
      chemoattraction of macrophages. DESIGN: Cross-sectional study. SETTING:
      University medical center. PATIENT(S): Women with leiomyoma (n = 32).
      INTERVENTION(S): Immunohistochemical analysis performed in the myometrium and
      leiomyoma of women receiving (n = 11) and not receiving (n = 21) GnRH-a
      treatment. MAIN OUTCOME MEASURE(S): The MCP-1 levels and macrophage counts
      determined by immunohistochemistry in the myometrium and leiomyoma of women
      receiving GnRH-a were compared to the levels and counts in women not receiving
      GnRH-a. RESULT(S): Samples from all 11 patients using GnRH-a revealed strong MCP
      1 staining, whereas staining was only weakly present in 11 and absent in 10
      samples from patients not receiving GnRH-a, revealing a significant difference in
      MCP-1 expression between GnRH-a users versus nonusers (P=.006). The number of
      tissue macrophages between GnRH-a users and nonusers was not significantly
      different. CONCLUSION(S): We found that there is an increase in the MCP-1 protein
      expression in the myometrium of women receiving GnRH-a treatment. On the other
      hand, we have not observed a difference in the macrophage count and distribution
      with GnRH-a treatment, suggesting a potentially direct antiproliferative role for
      MCP-1 rather than acting by means of chemoattraction of macrophages.

PMID- 11591414
TI  - Formation of pinopodes in human endometrium is associated with the concentrations
      of progesterone and progesterone receptors.
AB  - OBJECTIVE: To investigate the relation between the development of endometrial
      pinopodes and the serum concentration of hormones and the distribution of
      estrogen receptor-alpha, estrogen receptor-beta, progesterone receptor A, and
      progesterone receptor B. DESIGN: Prospective clinical study. SETTING: Hospital
      based unit of reproductive health and university-affiliated reproductive research
      laboratories. PATIENT(S): Twenty-seven healthy fertile women with normal
      menstrual cycles. INTERVENTION(S): Urine and blood sampling for hormone
      measurement, vaginal ultrasonography, and endometrial biopsy. MAIN OUTCOME
      MEASURE(S): Appearance of the endometrium on light microscopy, pinopode
      formation, serum levels of luteinizing hormone (LH) and follicle stimulating
      hormone (FSH), and expression of progesterone receptors A and B and estrogen
      receptors alpha and beta. RESULT(S): Pinopode formation and regression were
      closely associated with increases and decreases, respectively, in serum
      progesterone concentration. At pinopode development, levels progesterone
      receptors A and B in the glandular and luminal epithelial cells decreased; this
      effect was mainly dependent on the absence of progesterone receptor B. Serum
      estrogen levels and levels of estrogen receptor alpha and beta did not correlate
      with pinopode formation. CONCLUSION(S): The increase in serum progesterone level
      and down-regulation of progesterone receptor B are important in development of
      pinopodes.

PMID- 11591416
TI  - Distribution of Th1 and Th2 cell populations in human peripheral and decidual T
      cells from normal and anembryonic pregnancies.
AB  - OBJECTIVE: To examine whether maternal immune responses during normal pregnancy
      are Th2 biased and whether there are specific changes when anembryonic pregnancy
      occurs. DESIGN: Prospective study. SETTING: Department of Obstetrics and
      Gynecology at a university hospital. PATIENT(S): We studied 32 pregnant women
      receiving elective abortions of normal pregnancies and 35 women with anembryonic
      pregnancies between 6 weeks and 10 weeks of gestational age. INTERVENTION(S):
      Using the multilabeling capability of three-color flow cytometry, it is possible
      to measure intracellular cytokines and cell surface markers simultaneously to
      determine which cells are the cytokine-producing cells. MAIN OUTCOME MEASURE(S):
      We examined the extent and proportion of mononuclear cells expressing specific T
      cell surface markers and cytokines, interferon gamma, and interleukin 4 in the
      peripheral blood and deciduae. Secreted cytokines in the supernatants after 24
      hour culture were also compared. RESULT(S): During the unstimulated status, the
      proportion of IL-4-secreting cells significantly exceeded that of IFN-gamma
      secreting cells in the peripheral blood and decidua in normal pregnancies and was
      significantly decreased when anembryonic pregnancies occurred. Consequently, the
      Th1/Th2 ratios were increased during anembryonic pregnancies. However, after 24
      hour culture, only another Th2-type cytokine, IL-10, was markedly increased and
      exceeded IFN-gamma secretion in cultures from both the peripheral blood and
      decidua in normal pregnancies. CONCLUSION(S): The decidual T lymphocytes are Th2
      predominant. When anembryonic pregnancy occurs, this Th2 predominance disappears.

PMID- 11591417
TI  - Characterization of D1Pas1, a mouse autosomal homologue of the human AZFa region
      DBY, as a nuclear protein in spermatogenic cells.
AB  - OBJECTIVE: To gain insight into the function of D1Pas1 in spermatogenesis.
      DESIGN: The cellular and subcellular distribution of D1Pas1 protein were
      examined. SETTING: Academic research laboratory. ANIMALS: Swiss Webster and
      C57B1/6J mice. INTERVENTION(S): Antibodies were generated against a D1Pas1 fusion
      protein. Immunoblot analysis was performed on lysates of testicular cells
      separated into enriched populations of spermatogenic cells and fractionated into
      nuclear and cytoplasmic compartments. Immunohistochemistry was performed on
      histological sections of testis from adult and postnatal day 17 mice. MAIN
      OUTCOME MEASURE(S): D1Pas1 protein distribution. RESULT(S): D1Pas1 was expressed
      in germ cells, and its expression was developmentally regulated because it was
      detected specifically in the meiotic and postmeiotic haploid stages of
      spermatogenesis. D1Pas1 protein was predominantly localized in the nucleus, with
      weak cytoplasmic staining. CONCLUSION(S): Nuclear localization of D1Pas1 in the
      testis and its sequence homology to putative RNA helicases suggests a role of
      D1Pas1 in pre-mRNA processing during spermatogenesis. Germ cell expression of
      D1Pas1 and homology to the Y chromosome gene DBY, which is located in an area
      deleted in azoospermia, suggests a potential role for an autosomal gene in the
      regulation of spermatogenesis.

PMID- 11591419
TI  - Assessment of laparoscopic injuries by three methods.
AB  - OBJECTIVE: To compare laparoscopic, gross, and fluorescent assessment of
      laparoscopic pelvic injuries. DESIGN: Experimental prospective study. SETTING:
      Cleveland Clinic Foundation Animal Research Laboratory, Cleveland, Ohio.
      ANIMAL(S): Nonpregnant adult female pigs. INTERVENTION(S): Pelvic organs injured
      with laparoscopic energy sources were assessed laparoscopically, grossly, and
      with a fluorescent indicator and Wood's lamp. MAIN OUTCOME MEASURE(S): Three
      different measurements of each laparoscopic injury. RESULT(S): Assessment of
      injuries by laparoscopy did not differ significantly from gross assessment of
      injuries. In the segments of bowel and bladder that were injured with monopolar
      cautery, the Wood's lamp assessment of the injuries was significantly longer than
      the laparoscopic assessment of the injuries. CONCLUSION(S): Laparoscopic
      assessment of injured ureters, bowel, and bladder appear to be similar to gross
      assessment of these tissues. In tissue where the serosal surface is intact, the
      use of a fluorescent dye and a Wood's lamp provides a clear margin of the injured
      tissue.

PMID- 11591418
TI  - Transvaginal ovarian drilling: a new surgical treatment for improving the
      clinical outcome of assisted reproductive technologies in patients with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of transvaginal ovarian drilling (TVOD) in
      patients with polycystic ovary syndrome (PCOS) who were undergoing IVF treatment.
      DESIGN: Pilot study. SETTING: Reproductive medicine unit. PATIENT(S): Eleven
      patients with PCOS undergoing treatment with assisted reproductive technology
      (ART). INTERVENTION(S): Selection criterion for TVOD was repeated poor
      performance in > or =2 previous IVF cycles. MAIN OUTCOME MEASURE(S): Controlled
      ovarian hyperstimulation parameters, number of eggs collected, fertilization
      rate, embryo cleavage rate, implantation rate, pregnancy rate compared with the
      cycles before TVOD. RESULT(S): In the cycle after TVOD, a significantly higher
      dosage of FSH was used (33.5 +/- 12 IU vs. 52.2 +/- 15 IU) to collect a higher
      number of oocytes in the presence of similar E2 values at the day of hCG
      administration. This resulted in significantly higher fertilization and cleavage
      rates (27% vs. 66% and 54% vs. 72%, respectively). The pregnancy and the
      implantation rates after TVOD were similar to those for normovulatory patients
      undergoing IVF for tubal factor infertility during the study period.
      CONCLUSION(S): Our data suggest that the TVOD is effective in improving IVF
      results in difficult to treat patients with PCOS, and it is less invasive and
      less expensive when compared with laparoscopic ovarian diathermy.

PMID- 11591420
TI  - Avoidance of multiple pregnancies after ovulation induction by supernumerary
      preovulatory follicular reduction.
AB  - OBJECTIVE: To evaluate the effect of supernumerary preovulatory follicular
      reduction as an approach to avoid multiple pregnancies in ovulation induction or
      superovulation cycles. DESIGN: Retrospective study. SETTING: Tertiary referral
      center. PATIENT(S): In 26 cycles, 24 patients underwent ovulation induction or
      superovulation with either clomiphene citrate or hMG. INTERVENTION(S): Selective
      follicle aspiration was performed before hCG administration. MAIN OUTCOME
      MEASURE(S): Clinical pregnancy rate and numbers of multiple pregnancies.
      RESULT(S): A mean number of 4.5 follicles with a diameter > or =15 mm and a mean
      number of 4.5 follicles with a diameter < or =14 mm were observed before hCG
      administration. A mean number of 2.3 follicles with a diameter > or =15 mm and a
      mean number of 1.8 follicles with a diameter < or =14 mm were aspirated before
      the hCG administration. Seven singleton pregnancies (26.9% per cycle) ensued from
      the treatment. CONCLUSION(S): Aspiration of supernumerary follicles after
      ovulation induction or superovulation seems to be a valid approach to avoid
      multiple pregnancies without affecting pregnancy rate.

PMID- 11591421
TI  - Repeated freezing and thawing does not generally alter assay results for several
      commonly studied reproductive hormones.
AB  - OBJECTIVE: To determine the effect of repeated freezing and thawing, and storage
      temperature, on the assay results of commonly measured reproductive hormones, and
      sex hormone-binding globulin (SHBG) in human serum. DESIGN: Prospective
      laboratory study. SETTING: Academic medical center. PATIENT(S): Four men and
      three pregnant women in the third trimester. INTERVENTION(S): Pooled serum from
      men and pregnant females were frozen at either -20 degrees C or -70 degrees C.
      Aliquots were then subjected to repeat freeze/thaw cycles, from 1 to 10 times,
      and assays were performed after the final freeze/thaw cycle. MAIN OUTCOME
      MEASURE(S): Assay results for eight hormones (FSH, LH, PRL, androstenedione (A),
      17alpha-hydroxyprogesterone, P, insulin, and SHBG, as a function of the number of
      freeze/thaw cycles and storage temperature. RESULT(S): Only SHBG in male serum at
      -20 degrees C and P in pregnant serum at -70 degrees C showed statistically
      significant decreases in assay results with repeated freeze/thaw cycles (3.3% and
      1.1% per cycle, respectively). All other analytes did not show significant
      changes as a function of freeze/thaw cycles or storage temperature.
      CONCLUSION(S): There is no consistent or predictable alteration in the results of
      SHBG, or the glycoprotein and steroid hormones evaluated, as a function of
      repeated freeze/thaw or the storage temperature of human serum.

PMID- 11591422
TI  - Successful in vitro fertilization pregnancy after conservative management of
      endometrial cancer.
AB  - OBJECTIVE: To report a successful IVF pregnancy in an infertile couple after
      conservative treatment of endometrial cancer. DESIGN: Case report and literature
      review. SETTING: University teaching hospital. PATIENT(S): A 29-year-old
      infertile white woman. MAIN OUTCOME MEASURE(S): Successful pregnancy after
      conservative management of endometrial cancer. INTERVENTION(S): Grade 1
      endometrial adenocarcinoma diagnosed at hysteroscopy, followed by dilatation and
      curettage (D&C). On follow-up D&C, pathologic examination was normal after high
      dose progesterone therapy. The patient subsequently underwent an IVF cycle with
      transfer of three blastocysts. RESULT(S): The patient delivered triplets by
      cesarean section. Laparoscopic-assisted vaginal hysterectomy and bilateral
      salpingo-oophorectomy was then done. No residual endometrial cancer was evident
      in the hysterectomy specimen, but a 1.1-cm cystic mixed endometrioid and clear
      cell-type adenocarcinoma was discovered in the left ovary. The patient is doing
      well after 3 cycles of chemotherapy; her CA-125 level is normal. The triplets are
      also doing well. CONCLUSION(S): In carefully chosen situations, deferring surgery
      in infertile patients with endometrial cancer may be a viable option permitting
      subsequent successful pregnancy.

PMID- 11591423
TI  - Effect of pretreatment of semen with pokeweed antiviral protein on pregnancy
      outcome in the rabbit model.
AB  - OBJECTIVE: To determine whether artificial insemination of semen pretreated with
      pokeweed antiviral protein, a 29-kD antihuman immunodeficiency virus (HIV)
      protein purified from the leaves of Phytolacca americana, has any adverse effects
      on pregnancy outcome in the rabbit model. DESIGN: Prospective, controlled study.
      SETTING: Center for Advanced Preclinical Sciences at the Parker Hughes Institute.
      ANIMAL(S): Forty-eight female and 12 male New Zealand White rabbits.
      INTERVENTION(S): Fresh pooled semen obtained from 12 bucks was treated for 1 hour
      with and without 100 microg/mL or 1000 microg/mL pokeweed antiviral protein.
      Ovulated does in groups of 16 were artificially inseminated with control and
      pokeweed antiviral protein-treated semen and allowed to complete term pregnancy.
      MAIN OUTCOME MEASURE(S): Proportion of does that became pregnant and delivered
      newborn rabbits; the litter size, weight, growth, and viability of pups until
      lactation day 5. RESULT(S): Pokeweed antiviral protein treatment of semen had no
      adverse effect on gestation length, pregnancy rate, perinatal outcome, growth,
      and development of the offspring. CONCLUSION(S): Pokeweed antiviral protein shows
      clinical potential as a safe, prophylactic antiviral agent in assisted
      reproduction in HIV-1 discordant couples.

PMID- 11591424
TI  - Screening for mutations of the androgen receptor gene in patients with isolated
      cryptorchidism.
AB  - OBJECTIVE: To evaluate the occurrence of mutations of androgen receptor (AR) gene
      in patients with isolated cryptorchidism. DESIGN: Controlled clinical study.
      SETTING: Yamagata University Hospital, Yamagata and Tokyo Electric Power Company
      Hospital, Tokyo, Japan. PATIENT(S): Patients with isolated cryptorchidism (n =
      48) and a control group of men with normal phenotype (n = 20). INTERVENTION(S):
      Blood (lymphocyte DNA). MAIN OUTCOME MEASURE(S): Screening of the AR gene in
      exons 1-8 using single-strand conformational polymorphism analysis. RESULT(S): No
      abnormal band patterns were detected in patients with cryptorchidism or in
      control subjects within the eight exons of the AR gene. CONCLUSION(S): AR gene
      alterations appear to be an unlikely cause of isolated cryptorchidism.

PMID- 11591425
TI  - Demonstration of a mechanism of aneuploidy in human oocytes using Multifluor
      fluorescence in situ hybridization.
AB  - OBJECTIVE: To evaluate the potential of Multifluor fluorescence in situ
      hybridization (M-FISH) for karyotyping the human oocyte and first polar body.
      DESIGN: Prospective case study. SETTING: Research laboratories, university
      hospital. PATIENT(S): A 33-year-old woman with polycystic ovary syndrome who was
      undergoing ovarian stimulation and ICSI. MAIN OUTCOME MEASURE(S): Karyotyping of
      all chromosomes within an oocyte and first polar body, using GV stage oocytes
      matured to metaphase II in vitro. RESULT(S): Oocyte hyperploidy was diagnosed by
      M-FISH to be 23, X +15 cht +19 cht +22 cht. The correspond- ing polar body was
      hypoploid, with a karyotype of 23, X -15 cht -19 cht -22 cht. This was due to
      unbalanced predivision at meiosis I. Reprobing confirmed karyotype assignments
      for chromosomes X, 13, 18, and 21. CONCLUSION(S): The mechanism involved in
      maternally derived aneuploidy can be defined by using M-FISH to simultaneously
      karyotype both oocyte and first polar body chromosomes at metaphase II.
      Multifluor FISH may be useful for investigative studies of maternally derived
      aneuploidy, which is a major cause of preimplantation waste in natural and
      assisted reproduction.

PMID- 11591426
TI  - Live birth after sperm retrieval from a moribund man.
AB  - OBJECTIVE: To report a live birth with IVF-ET and intracytoplasmic sperm
      injection (ICSI) using sperm retrieved from a moribund man being maintained on
      life support systems. DESIGN: Case report. SETTING: Nonprofit private teaching
      hospitals. PATIENT(S): A 27-year-old man who was decorticate after an accident.
      INTERVENTION(S): Epididymal sperm retrieval and sperm cryopreservation, pastoral
      psychologic counseling, and subsequent IVF-ET with ICSI. MAIN OUTCOME MEASURE(S):
      Pregnancy and delivery. RESULT(S): Birth of a healthy child after IVF-ET with
      ICSI and single blastocyst transfer. CONCLUSION(S): First report in peer-reviewed
      medical literature of a live birth after sperm retrieval from a moribund man.

PMID- 11591427
TI  - Is coasting effective for preventing ovarian hyperstimulation syndrome in
      patients receiving a gonadotropin-releasing hormone antagonist during an in vitro
      fertilization cycle?
AB  - OBJECTIVE: To report two cases of coasting during receipt of GnRH antagonists.
      DESIGN: Case report. SETTING: University hospital. PATIENT(S): One 27-year-old
      and one 28-year-old woman, both with risk factors for the ovarian
      hyperstimulation syndrome (OHSS). INTERVENTION(S): Two IVF treatments during
      which hMG treatment was stopped until E2 decreased to a safer level during
      receipt of GnRH antagonist. MAIN OUTCOME MEASURE(S): Development of OHSS and
      pregnancy. RESULT(S): Embryos were transferred in both women. Neither woman
      developed OHSS and one ongoing pregnancy was obtained. CONCLUSION(S): Coasting is
      feasible when a GnRH antagonist is used during IVF. Further studies are needed to
      evaluate its preventive role in OHSS.

PMID- 11591428
TI  - Relationship of parental trauma exposure and PTSD to PTSD, depressive and anxiety
      disorders in offspring.
AB  - This study examined the relationship of parental trauma exposure and PTSD to the
      development of posttraumatic stress disorder (PTSD), depressive and anxiety
      disorders in the adult offspring of Holocaust survivors. One hundred and thirty
      five subjects (55 men and 80 women) were divided into three groups according to
      parental trauma exposure and PTSD: 60 subjects were offspring of Holocaust
      survivors who endorsed having at least one parent with PTSD, 33 were offspring of
      Holocaust survivors who reported having no parent with PTSD, and 42 were
      demographically similar subjects with no parental Holocaust exposure. All
      subjects underwent a comprehensive psychiatric interview in which information
      about lifetime psychiatric diagnoses and exposure to traumatic events was
      obtained. Subjects also completed a checklist based on the 17 DSM-IV symptoms of
      PTSD, to estimate the symptom severity of PTSD in their parents. A presumptive
      diagnosis of parental PTSD was assigned according to DSM-IV criteria. Forward and
      forced entry stepwise logistic regression analyses were used to determine the
      effects of parental exposure, parental PTSD, and the subject's own history of
      trauma in the development of PTSD, depressive, and anxiety disorders in the
      offspring. The findings demonstrate a specific association between parental PTSD
      and the occurrence of PTSD in offspring. Additionally, parental trauma exposure,
      more than parental PTSD, was found to be significantly associated with lifetime
      depressive disorder. The identification of parental PTSD as a risk factor for
      PTSD in offspring of Holocaust survivors defines a sample in which the biological
      and psychological correlates of risk for PTSD can be further examined.

PMID- 11591429
TI  - Reduced olfactory performance in patients with major depression.
AB  - The aim of the present study is to investigate olfactory sensitivity and odor
      evaluations in a homogeneous sample of unipolar depressive patients using pure
      olfactory odors. Twenty-four in-patients with major depressive disorder (MDD)
      were investigated during their acute depressive phase. Eighteen of them
      participated a second time after successful treatment. A group of healthy
      subjects, matched by age, sex, and smoking behavior, served as a control.
      Olfactory sensitivity, as measured by threshold tests, was strongly reduced in
      patients with severe depression. Additional correlative analyses revealed that
      the lowered sensitivity could partly be predicted by high depression scores.
      After successful medical treatment, these sensitivity differences were reduced
      and did not reach the significance level. The subjective odor evaluations
      (valence and intensity ratings) were not markedly changed in general. The results
      reveal that olfactory performance in MDD patients is reduced at an early
      perceptional level of stimulus processing. It is discussed whether this effect
      can be attributed to the close functional connection between the main olfactory
      bulb and the amygdala.

PMID- 11591430
TI  - Panic disorder: the role of the balance system.
AB  - Experimental evidences suggest that Panic Disorder (PD) is characterized by
      abnormalities in respiratory and vestibular functions. We studied balance system
      function in patients with PD and its relationships with CO(2) reactivity and
      clinical characteristics. Nineteen patients with PD with/without agoraphobia
      underwent static posturography and the 35% CO(2) challenge. The severity of
      clinical symptomatology was measured by standardized psychometric scales.
      Patients were free of psychotropic medications during the 2 weeks before the
      study. Different investigators blind to each other carried out the CO(2)
      challenge, static posturography and clinical assessment. Nineteen age and sex
      matched healthy controls underwent static posturography. Body sway velocity and
      length were significantly higher in panic patients than in controls and patients
      showed high percentages of abnormal scores. Patients with two or more abnormal
      scores on static posturography were significantly more agoraphobic than those
      with less than two. Abnormal posturography scores under the eyes-opened was
      related to high anticipatory anxiety, whereas those under eyes-closed was related
      to phobic avoidance. Symptomatological reactivity to CO(2) was significantly
      correlated to abnormal functions of the balance system in the eyes-closed
      condition. Our findings suggest that (1) many patients with PD (5-42%) have
      abnormalities in their balance system function compared with healthy controls (0
      5%), (2) symptomatological reactivity to CO(2) and balance system function in
      patients with PD are correlated only in the eyes-closed condition and (3) there
      is a significant link between agoraphobic avoidance and subclinical abnormal
      function of the balance system network.

PMID- 11591431
TI  - CSF thyrotropin-releasing hormone concentrations differ in patients with
      schizoaffective disorder from patients with schizophrenia or mood disorders.
AB  - OBJECTIVE: To determine if there were differences in CSF-TRH concentrations among
      several acute major psychiatric disorders and to investigate the effects of
      antipsychotic treatment on CSF-TRH levels. METHOD: CSF-TRH concentrations were
      measured in 62 psychiatric inpatients during an acute phase of illness after a
      drug-free period. CSF-TRH measurements were repeated in 14 of these patients
      after 4 weeks of antipsychotic treatment. RESULTS: Post-hoc tests (Tukey HSD)
      revealed significant differences among patients with schizoaffective disorder and
      both schizophrenia (P<0.03) and major depression (P<0.01). There were no
      significant differences between pre and posttreatment levels of CSF-TRH in the 14
      patients treated with conventional agents for 4 weeks (1.54 pg/ml vs. 1.47
      pg/ml). However, patients with a reduction in CSF-TRH concentration had a
      significantly better symptom response measured by the Brief Psychiatric Rating
      Scale (BPRS) positive factor (61% in six subjects) vs. those who had an increase
      in posttreatment CSF-TRH (29% in eight subjects; t=2.2; d.f.=12; P<0.04).
      CONCLUSIONS: These results provide further evidence for a neuromodulatory role
      for TRH and suggest a re-examination of its behavioral effects and interactions
      with brain neurotransmitter systems relevant to major psychotic and mood
      disorders.

PMID- 11591432
TI  - Reliability and validity of the Panic Disorder Severity Scale: replication and
      extension.
AB  - The Panic Disorder Severity Scale (PDSS) is a recently developed seven-item
      instrument to rate overall severity of Panic Disorder. The scale has previously
      shown good psychometric properties in a sample of Panic Disorder patients with no
      more than mild agoraphobia. The purpose of this paper is to confirm reliability
      and validity, to provide an estimate of a cut-score discriminating the presence
      or absence of current DSM-IV Panic Disorder, and to determine the factor
      structure of the instrument. PROCEDURES: 104 psychiatric outpatients, including
      54 with current Panic Disorder, underwent structured diagnostic assessment and
      the PDSS interview. The PDSS was repeated within 3-17 days. RESULTS: we confirmed
      reliability and validity of the instrument and found a one-factor solution fit
      the data. A cut-off score of eight identifies patients with current panic with a
      sensitivity of 83.3%, and a specificity of 64%. CONCLUSION: the PDSS is a simple,
      reliable instrument for use in Panic Disorder studies. A cut-score of eight may
      be useful as a tool to screen patients in settings such as primary care, for
      diagnosis-level symptoms.

PMID- 11591433
TI  - Maintaining reliability in a long-term psychiatric study: an ongoing inter-rater
      reliability monitoring program using the longitudinal interval follow-up
      evaluation.
AB  - The Longitudinal Interval Follow-up Evaluation (LIFE), has been shown to be a
      valid and reliable instrument for characterizing the week-by-week course of
      anxiety disorders examined retrospectively over the period of 1 year. Due to the
      chronic nature of these disorders, there is a need for reliable, valid
      instruments for measuring course over periods of several years if we are to learn
      more about the natural history of these disorders. This paper describes a rater
      monitoring program designed to ensure long-term inter-rater reliability and
      prevent "rater drift". In this program, clinical interviewers score taped
      interviews and are required to maintain a median intra-class correlation
      coefficient (ICC) of at least 0.80 with the other raters. Raters also assess
      tapes from previous years, to ensure that they are using the same diagnostic
      criteria as earlier generations of interviewers. A reliability study was
      conducted to compare psychiatric status ratings (PSRs) collected using biweekly
      telephone interviews with the semi-annual interviews. The ICCs for panic,
      agoraphobia, social phobia, and generalized anxiety disorder were very good to
      excellent. Another reliability study examined the PSRs of subjects who had been
      previously lost to follow-up. ICCs for panic, agoraphobia, generalized anxiety
      disorder and depression were good to excellent. These results show that the LIFE,
      when used in conjunction with an intensive training and rater monitoring system,
      is a reliable instrument for use in longitudinal studies of the course of anxiety
      disorders.

PMID- 11591434
TI  - Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators
      of lipid synthetic genes.
AB  - Roles of sterol regulatory element-binding proteins (SREBPs) have been
      established as lipid synthetic transcription factors especially for cholesterol
      and fatty acid synthesis. SREBPs have unique characteristics. Firstly, they are
      membrane-bound proteins and the N-terminal active portions enter nucleus to
      activate their target genes after proteolytic cleavage, which requires sterol
      sensing molecule, SREBP-activating protein (SCAP) and is crucial for sterol
      regulation. Secondly, they bind and activate sterol-regulatory (SREs) containing
      promoters as well as some E-boxes, which makes SREBPs eligible to regulate a wide
      range of lipid genes. Finally, three isoforms, SREBP-1a-1c, and have different
      roles in lipid synthesis. In vivo studies using transgenic and knockout mice
      suggest that SREBP-1 seems to be involved in energy metabolism including fatty
      acid and glucose/insulin metabolism, whereas SREBP-2 is specific to cholesterol
      synthesis. Future studies will be focused on understanding molecular mechanisms
      sensing cellular sterol and energy states where SREBPs are deeply involved.

PMID- 11591435
TI  - Human metabolism of phytanic acid and pristanic acid.
AB  - Phytanic acid is a methyl-branched fatty acid present in the human diet. Due to
      its structure, degradation by beta-oxidation is impossible. Instead, phytanic
      acid is oxidized by alpha-oxidation, yielding pristanic acid. Despite many
      efforts to elucidate the alpha-oxidation pathway, it remained unknown for more
      than 30 years. In recent years, the mechanism of alpha-oxidation as well as the
      enzymes involved in the process have been elucidated. The process was found to
      involve activation, followed by hydroxylase, lyase and dehydrogenase reactions.
      Part, if not all of the reactions were found to take place in peroxisomes. The
      final product of phytanic acid alpha-oxidation is pristanic acid. This fatty acid
      is degraded by peroxisomal beta-oxidation. After 3 steps of beta-oxidation in the
      peroxisome, the product is esterified to carnitine and shuttled to the
      mitochondrion for further oxidation. Several inborn errors with one or more
      deficiencies in the phytanic acid and pristanic degradation have been described.
      The clinical expressions of these disorders are heterogeneous, and vary between
      severe neonatal and often fatal symptoms and milder syndromes with late onset.
      Biochemically, these disorders are characterized by accumulation of phytanic
      and/or pristanic acid in tissues and body fluids. Several of the inborn errors
      involving phytanic acid and/or pristanic acid metabolism have been characterized
      on the molecular level.

PMID- 11591436
TI  - Lipid biosynthesis as a target for antibacterial agents.
AB  - Fatty acid biosynthesis, the first stage in membrane lipid biogenesis, is
      catalyzed in most bacteria by a series of small, soluble proteins that are each
      encoded by a discrete gene (Fig. 1; Table 1). This arrangement is termed the type
      II fatty acid synthase (FAS) system and contrasts sharply with the type I FAS of
      eukaryotes which is a dimer of a single large, multifunctional polypeptide. Thus,
      the bacterial pathway offers several unique sites for selective inhibition by
      chemotherapeutic agents. The site of action of isoniazid, used in the treatment
      of tuberculosis for 50 years, and the consumer antimicrobial agent triclosan were
      revealed recently to be the enoyl-ACP reductase of the type II FAS. The fungal
      metabolites, cerulenin and thiolactomycin, target the condensing enzymes of the
      bacterial pathway while the dehydratase/isomerase is inhibited by a synthetic
      acetylenic substrate analogue. Transfer of fatty acids to the membrane has also
      been inhibited via interference with the first acyltransferase step, while a new
      class of drugs targets lipid A synthesis. This review will summarize the data
      generated on these inhibitors to date, and examine where additional efforts will
      be required to develop new chemotherapeutics to help combat microbial infections.

PMID- 11591437
TI  - Gene structure, intracellular localization, and functional roles of sterol
      carrier protein-2.
AB  - Since its discovery three decades ago, sterol carrier protein-2 (SCP-2) has
      remained a fascinating protein whose physiological function in lipid metabolism
      remains an enigma. Its multiple proposed functions arise from its complex gene
      structure, post-translational processing, intracellular localization, and ligand
      specificity. The SCP-2 gene has two initiation sites coding for proteins that
      share a common 13 kDa SCP-2 C-terminus: (1) One site codes for 58 kDa SCP-x which
      is partially post-translationally cleaved to 13 kDa SCP-2 and a 45 kDa protein.
      (2) A second site codes for 15 kDa pro-SCP-2 which is completely post
      translationally cleaved to 13 kDa SCP-2. Very little is yet known regarding how
      the relative proportions of the two transcripts are regulated. Although all three
      proteins contain a C-terminal SKL peroxisomal targeting sequence, it is unclear
      why all three proteins are not exclusively localized in peroxisomes. However, the
      recent demonstration that the SCP-2 N-terminal presequence in pro-SCP-2
      dramatically modulated the intracellular targeting coded by the C-terminal
      peroxisomal targeting sequence may account for the observation that as much as
      half of total SCP-2 is localized outside the peroxisome. The tertiary and
      secondary structure of the 13 kDa SCP-2, but not that of 15 kDa pro-SCP-2 and 58
      kDa SCP-x, are now resolved. Increasing evidence suggests that the 58 kDa SCP-x
      and 45 kDa proteins are peroxisomal 3-ketoacyl-CoA-thiolases involved in the
      oxidation of branched chain fatty acids. Since 15 kDa pro-SCP-2 is post
      translationally completely cleaved to 13 kDa SCP-2, relatively little attention
      has been focused on this protein. Finally, although the 13 kDa SCP-2 is the most
      studied of these proteins, because it exhibits diversity of its ligand partners
      (fatty acids, fatty acyl CoAs, cholesterol, phospholipids), new potential
      physiological function(s) are still being proposed and questions regarding
      potential compensation by other proteins with overlapping specificity are only
      beginning to be resolved.

PMID- 11591438
TI  - The direct visuo-motor pathway in mammalian superior colliculus; novel
      perspective on the interlaminar connection.
AB  - The mammalian superior colliculus (SC) is a center controlling the orienting
      behaviors such as saccadic eye movements. The superficial layers receive visual
      inputs and the deeper layers send descending motor command to the brainstem and
      spinal cord. Existence of the interlaminar connection from the superficial to the
      deeper layers has been an issue of debate during the last two decades. Recent
      studies have proved the existence of the interlaminar connection by introducing
      the in vitro slice preparations. When the collicular circuit is disinhibited from
      gamma-amino butyric acid A (GABA(A)) receptor-mediated inhibition, the signal
      transmission through the interlaminar connection is enormously facilitated and
      neurons in the deeper layers exhibit bursting response to stimulation of the
      superficial layer with non-linear amplification mechanism that depends on the
      activation of NMDA-type glutamate receptors. In addition, the cholinergic input
      to the intermediate layer lowers the threshold for the bursting response and
      facilitates the transmission through the interlaminar connection via activation
      of nicotinic receptors. The signal transmission through the interlaminar
      connection may lead to execution of extremely short latency saccades called
      express saccades.

PMID- 11591439
TI  - The effects of dopamine and its antagonists on directional delay-period activity
      of prefrontal neurons in monkeys during an oculomotor delayed-response task.
AB  - To examine the role of dopamine receptors in the memory field of neurons for
      visuospatial working memory in the prefrontal cortex (PFC), dopamine and its
      antagonists (SCH23390 for the D1-antagonist and sulpiride for the D2-antagonist)
      were applied iontophoretically to neurons of the dorsolateral PFC in monkeys that
      performed an oculomotor delayed-response task. In this task, the subject made a
      memory-guided saccade to a remembered target location that had been cued by a
      visuospatial stimulus (right, up, left, or down; 15 degrees in eccentricity)
      prior to a 4-s delay period. We focused here on PFC neurons that showed
      directional delay-period activity; i.e., an increased activity during the delay
      period, the magnitude of which varied significantly with the target location.
      Iontophoretic application of SCH23390 (usually 50 nA) decreased or increased the
      activities of most of these neurons (n=48/62, 77%); most neurons showed a
      decrease (n=43/62, 69%). For the neurons affected by SCH23390, a directional
      index of directional delay-period activity was attenuated by SCH23390, whereas
      the preferred direction was not greatly affected. The decreasing effect of
      SCH23390 was dose-dependent; the extent of the decrease was less with a lower
      dose (20-nA current) than with the ordinary dose (50-nA current), although the
      effect of the lower dose of SCH23390 on delay-period activity was similar in
      nature to that of the ordinary dose of SCH23390. Furthermore, the application of
      dopamine itself augmented directional delay-period activity in most of the
      neurons tested (n=12/16, 75%). Sulpiride did not have any significant effects in
      most of the neurons tested (n=15/17). These results suggest that the activation
      of D1-dopamine receptors play a facilitating role in the memory field of PFC
      neurons for visuospatial working memory processes.

PMID- 11591440
TI  - Serotonin-induced nitric oxide production in the ventral nerve cord of the
      earthworm, Eisenia fetida.
AB  - Effect of serotonin on nitric oxide (NO) production in the ventral nerve cord
      (VNC) of the earthworm Eisenia fetida was investigated by a bio-imaging and an
      electrochemical technique. In the bio-imaging, the spatial pattern of NO
      production in VNC was visualized using an NO-specific fluorescent dye,
      diaminofluorescein-2 diacethyl (DAF-2 DA). Application of serotonin (100 microM)
      increased NO production in VNC by about 65% (P<0.05), compared with basal NO
      production. The increase was mainly from the nitergic neurons in the ventral side
      of VNC. In the electrochemical technique, real-time basal and serotonin-induced
      NO production was estimated with an NO-specific electrode. On the ventral surface
      of VNC, the estimated basal NO production was stable at 200+/-52 nM, and was
      transiently augmented to 840+/-193 nM by the addition of 10 microM serotonin. In
      conclusion, the estimated basal NO production in the earthworm VNC is relatively
      high compared with other nervous systems earlier reported, and transiently
      augmented by serotonin. Our results suggest that NO signaling in VNC is involved
      in neuromodulation by serotonin.

PMID- 11591441
TI  - Neurones in the cervical enlargement of the cat spinal cord antidromically
      activated from sacral segments and the inferior cerebellar peduncle.
AB  - The electrophysiological investigation of neurones located in the cervical
      enlargement of the spinal cord was performed in eight-chloralose anaesthetized
      cats. Neurones were recorded intracellularly or extracellularly and identified by
      antidromic stimulation. The main purpose of the study was to test whether these
      neurones give off collateral branches ascending to the inferior cerebellar
      peduncle and descending to the sacral segments (S1/S2). Recordings were made from
      78 neurones located in medial and central parts of Rexed's laminae VII and VIII
      of C6/C7 segments. Four subpopulations could be distinguished from their patterns
      of propriospinal or supraspinal projections: (a) ascending/descending neurones
      with axons ascending to RB and descending to S1/S2 (23%); (b)
      ascending/descending neurones projecting to RB and the level of Th13 (14%); (c)
      propriospinal neurones descending to Th13 (15%); (d) propriospinal neurones
      descending to S1/S2 (48%). Within these groups, ipsilateral, contralateral and
      bilateral descending projections were observed. The mean axonal conduction
      velocities for descending and ascending collaterals of bidirectional neurones
      were 59 and 39 m/s, respectively. Results suggest that parallel transmission of
      information to supraspinal and spinal centres plays an important role in the
      process of movement coordination.

PMID- 11591442
TI  - Oxytocin mediates the inhibitory action of acute lithium on the morphine
      dependence in rats.
AB  - The role of central oxytocin in inhibitory action of lithium on the development
      of morphine dependence was behavioral investigated in rats. Acute lithium could
      enhance the morphine-induced analgesia in rats with or without chronic morphine
      treatment; this effect could be inhibited by intraventricular injection of
      oxytocin antagonist d (CH(2))(5)-Tyr (Me)-[Orn(8)]-Vasotocin (OVT). Lithium could
      attenuate naloxone-precipitated withdrawal signs in morphine dependent rats. The
      reduction of the expression of naloxone-precipitated withdrawal signs by lithium
      was reversed by ICV of OVT. The lithium significantly inhibited the conditioned
      place preference (CPP) induced by morphine, which inhibitory action of lithium
      could also reverse by ICV injection of OVT. These results suggested that lithium
      might inhibit the physical dependence on morphine as well as psychological
      dependence in rats, and that this inhibitory effect of lithium on the development
      of morphine dependence might be associated with oxytocin systems in the central
      nervous system.

PMID- 11591443
TI  - Electrophysiological and ultrastructural changes in severed motor axons of the
      crayfish.
AB  - In many invertebrates, distal stumps of severed axons degenerate slowly and
      survive for long periods of time; this lengthy process allows the study of the
      physiological and structural changes involved in axonal degeneration processes.
      The following experiments demonstrate a reduction in EPSP amplitude, an increase
      in the distance between neighboring release sites, an extended duration of
      transmitter release, and a doubling in the average number of quanta released per
      stimulus at each release site. Ultrastructural examination of those stumps
      revealed various degrees of glial cell invasion. In the same distal stump, some
      axons were partially filled with glial cells, but adjacent axons could be
      completely filled by them. Glial cell invasion was greater at regions closer to
      the site of axotomy and increased as time progressed. The glia engulfing the
      stumps exhibited hypertrophy and changes in nuclear morphology. The nuclei of
      some of those glia cells were unusually close to the axonal membrane in the
      distal stumps. In spite of these severe morphological changes, the stumps were
      still capable of conducted action potentials and releasing transmitter at their
      synapses.

PMID- 11591444
TI  - Dendritic spatial flicker of local membrane potential due to channel noise and
      probabilistic firing of hippocampal neurons in culture.
AB  - Whole-cell recordings and imaging of dissociated hippocampal neurons stained with
      voltage sensitive dye provide a new microscopic picture of neuronal excitation.
      This is the first attempt to combine imaging of active channel clusters on the
      geometry of live neurons and a theoretical approach. During single somatic action
      potentials and the back-invasion into the neurites, local mean potentials are
      generated at sites of active channel clusters which are unevenly distributed in
      the neuronal membrane. Similar mean membrane potentials are observed in the
      neurites and at the soma. Identical action potentials produce different spatial
      patterns of mean membrane potentials from trial to trial. This spatial
      variability is explained by the stochastic behavior of the channels in the
      clusters. When hippocampal neurons are excited by synaptic inputs, their evoked
      responses are probabilistic and generate variable spatial patterns of mean
      membrane potential trial after trial. Our stochastic model reproduces this random
      behavior by assuming that the voltage fluctuations generated by channel noise are
      added to the synaptic potentials reaching the soma. We demonstrate that the
      probability of action potential initiation depends on the strength of the
      synaptic input, the diameter of the dendrites and the relative positions of the
      channel clusters, of the synapse and of the soma.

PMID- 11591445
TI  - Nonlinear analysis of orthostatic posture in patients with vertigo or balance
      disorders.
AB  - The stabilometry signals involve irregular and unpredictable components. In order
      to identify the hidden dynamics that underlie the multi-link networks consisted
      of the multiple sensory systems, motor components and central integration, we
      applied a nonlinear analysis to these signals. We evaluated the postural control
      differences between eyes open and closed by means of the dynamical closeness
      between two states, known as similarity index, for the patients with vestibular
      disorders. We were able to demonstrate that some patients (eight of 21) showed a
      difference between the conventional and nonlinear measures. Especially, the
      similarity index tended to reflect the clinical course of the vestibular
      compensation and the findings in the patients with benign paroxysmal positional
      vertigo (BPPV) demonstrated that its vestibular function may include various
      pathologies besides canalithiasis. These results suggest that nonlinear analysis
      can elucidate the complex postural control networks and this procedure may also
      be able to provide the new findings of the stabilometry examinations.

PMID- 11591446
TI  - The Lurcher mutation reveals Ca(2+) permeability and PKC modification of the
      GluRdelta channels.
AB  - The physiological function of the GluRdelta subfamily which is one of the
      glutamate receptor (GluR) channel subunits has not yet been clarified, because no
      GluR channel activity has been detected in heterologous expression systems. The
      Lurcher mutation, a point mutation of the GluRdelta2 subunit, converts it into a
      constitutively active and cation-permeating channel. We introduced this mutation
      into GluRdelta1 and GluRdelta2, AMPA-selective, and NMDA-selective GluR channel
      subunits, and characterized their channel properties. It was shown that the
      Lurcher mutation alters the gating properties of AMPA- and NMDA-selective GluR
      channels, but not their cation permeabilities nor metabolic modulations. These
      findings support the idea that the Lurcher mutant homomeric GluRdelta1 channels
      are permeable to Ca(2+) as do the mutant GluRdelta2 channels, reflecting their
      original channel properties. We also found that cation permeability of the mutant
      GluRdelta1 channels was decreased by TPA, a protein kinase C activator. It
      indicates the possibility that phosphorylation by PKC activation may inhibit
      channel with wild-type GluRdelta1 subunit.

PMID- 11591447
TI  - Inhibitory effect of histamine on axonal transport in cultured mouse dorsal root
      ganglion neurons.
AB  - Histamine is important in mediating peripheral sensory information such as
      inflammation, allergic hypersensitivity, and itch. In the present study, using
      video-enhanced microscopy, we investigated the effect of histamine on axonal
      transport in cultured dorsal root ganglion (DRG) neurons of the mouse.
      Application of histamine (100 microM) reversibly reduced the number of particles
      transported within neurites in both anterograde and retrograde directions. The
      histamine H(1)-receptor agonist 2-thiazolylethylamine (100 microM) and the H(3)
      receptor agonist R-alpha-methylhistamine (100 microM) also reduced anterograde
      and retrograde axonal transport, whereas the histamine H(2)-receptor agonist
      dimaprit (100-1000 microM) had no effect. The effect of histamine was partially
      blocked by pretreatment with H(1)-receptor antagonist pyrilamine (1 microM) or
      the H(3)-receptor antagonist thioperamide (1 microM). Pretreatment with a
      combination of pyrilamine (1 microM) and thioperamide (1 microM) completely
      blocked the response to histamine. The H(2)-receptor antagonist cimetidine (1
      microM) was ineffective. These results suggest that histamine inhibits axonal
      transport of cultured mouse DRG neurons via the activation of H(1)- and H(3)
      receptors.

PMID- 11591448
TI  - Apoptosis regulators and their role in tumorigenesis.
AB  - It has become clear that, together with deregulated growth, inhibition of
      programmed cell death (PCD) plays a pivotal role in tumorigenesis. In this
      review, we present an overview of the genes and mechanisms involved in PCD. We
      then summarize the evidence that impaired PCD is a prerequisite for
      tumorigenesis, as indicated by the fact that more and more neoplastic mutations
      appear to act by interfering with PCD. This has made the idea of restoration of
      corrupted 'death programs' an intriguing new area for potential cancer therapy.

PMID- 11591449
TI  - The Id proteins: targets for inhibiting tumor cells and their blood supply.

PMID- 11591450
TI  - Comparative immunohistochemical localisation of GABA(B1a), GABA(B1b) and GABA(B2)
      subunits in rat brain, spinal cord and dorsal root ganglion.
AB  - GABA(B) receptors are G-protein-coupled receptors mediating the slow onset and
      prolonged synaptic actions of GABA in the CNS. The recent cloning of two genes,
      GABA(B1) and GABA(B2), has revealed a novel requirement for GABA(B) receptor
      signalling. Studies have demonstrated that the two receptor subunits associate as
      a GABA(B1)/GABA(B2) heterodimer to form a functional GABA(B) receptor. In this
      study we have developed polyclonal antisera specific to two splice variants of
      the GABA(B1) subunit, GABA(B1a) and GABA(B1b), as well as an antiserum to the
      GABA(B2) subunit. Using affinity-purified antibodies derived from these antisera
      we have mapped out the distribution profile of each subunit in rat brain, spinal
      cord and dorsal root ganglion. In brain the highest areas of GABA(B1a), GABA(B1b)
      and GABA(B2) subunit expression were found in neocortex, hippocampus, thalamus,
      cerebellum and habenula. In spinal cord, GABA(B1) and GABA(B2) subunits were
      expressed in the superficial layers of the dorsal horn, as well as in motor
      neurones in the deeper layers of the ventral horn. GABA(B) receptor subunit
      immunoreactivity in dorsal root ganglion suggested that expression of GABA(B1b)
      was restricted to the large diameter neurones, in contrast to GABA(B1a) and
      GABA(B2) subunits which were expressed in both large and small diameter neurones.
      Although expression levels of GABA(B1) and GABA(B2) subunits varied we found no
      areas in which GABA(B1) was expressed in the absence of GABA(B2). This suggests
      that most, if not all, GABA(B1) immunoreactivity may represent functional GABA(B)
      receptors. Although our data are in general agreement with functional studies,
      some discrepancies in GABA(B1) subunit expression occurred with respect to other
      immunohistochemical studies. Overall our data suggest that GABA(B) receptors are
      widely expressed throughout the brain and spinal cord, and that GABA(B1a) and
      GABA(B1b) subunits can associate with GABA(B2) to form both pre- and post
      synaptic receptors.

PMID- 11591451
TI  - Autoradiographic mapping of the opioid receptor-like 1 (ORL1) receptor in the
      brains of mu-, delta- or kappa-opioid receptor knockout mice.
AB  - The opioid receptor-like 1 (ORL1) receptor shares a high degree of sequence
      homology with the classical mu-, delta- and kappa-opioid receptors and a
      functional mutual opposition between these receptors has been suggested. To
      further address this possible interaction we have used mu-, delta- and kappa
      opioid receptor knockout mice to determine autoradiographically if there are any
      changes in the number or distribution of the ORL1 receptor, labelled with
      [(3)H]nociceptin, in the brains of mice deficient in each of the opioid
      receptors. An up-regulation of ORL1 expression was observed across all brain
      regions in delta-knockouts with cortical regions typically showing a 15-30%
      increase in binding that was most marked in heterozygous mice. In contrast, ORL1
      receptor expression was down-regulated in virtually all brain structures in
      heterozygous kappa-knockouts although the magnitude of this change was not as
      great as for the delta-knockouts. No significant alterations in ORL1 receptor
      expression were observed across brain regions in mu-receptor knockout mice and
      there were no qualitative differences in ORL1 receptor expression in any groups.
      These data suggest there are interactions between the ORL1 system and the
      classical opioid receptors and that the interactions are receptor-specific. The
      greater differences observed in heterozygous mice suggest that these interactions
      might be most relevant when there is only partial loss of receptor function.

PMID- 11591452
TI  - Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS:
      differential location relative to pre- and postsynaptic sites.
AB  - The metabotropic glutamate receptors (mGluRs) have distinct distribution patterns
      in the CNS but subtypes within group I or group III mGluRs share similar
      ultrastructural localization relative to neurotransmitter release sites: group I
      mGluRs are concentrated in an annulus surrounding the edge of the postsynaptic
      density, whereas group III mGluRs are concentrated in the presynaptic active
      zone. One of the group II subtypes, mGluR2, is expressed in both pre- and
      postsynaptic elements, having no close association with synapses. In order to
      determine if such a distribution is common to another group II subtype, mGluR3,
      an antibody was raised against a carboxy-terminus of mGluR3 and used for light
      and electron microscopic immunohistochemistry in the mouse CNS. The antibody
      reacted strongly with mGluR3, but it also reacted, though only weakly, with
      mGluR2. Therefore, to examine mGluR3-selective distribution, we used mGluR2
      deficient mice as well as wild-type mice. Strong immunoreactivity for mGluR3 was
      found in the cerebral cortex, striatum, dentate gyrus of the hippocampus,
      olfactory tubercle, lateral septal nucleus, lateral and basolateral amygdaloid
      nuclei, and nucleus of the lateral olfactory tract. Pre-embedding
      immunoperoxidase and immunogold methods revealed mGluR3 labeling in both
      presynaptic and postsynaptic elements, and also in glial profiles. Double
      labeling revealed that the vast majority of mGluR3 in presynaptic elements is not
      closely associated with glutamate and GABA release sites in the striatum and
      thalamus, respectively. However, in the spines of the dentate granule cells, the
      highest receptor density was found in perisynaptic sites (20% of immunogold
      particles within 60 nm from the edge of postsynaptic membrane specialization)
      followed by a decreasing receptor density away from the synapses (to
      approximately 5% of particles per 60 nm). Furthermore, 19% of immunogold
      particles were located in asymmetrical postsynaptic specialization, indicating an
      association of mGluR3 to glutamatergic synapses. The present results indicate
      that the localization of mGluR3 is rather similar to that of group I mGluRs in
      the postsynaptic elements, suggesting a unique functional role of mGluR3 in
      glutamatergic neurotransmission in the CNS.

PMID- 11591453
TI  - Expression of R-cadherin and N-cadherin by cell groups and fiber tracts in the
      developing mouse forebrain: relation to the formation of functional circuits.
AB  - The expression of R-cadherin and N-cadherin was mapped in the postnatal forebrain
      of the mouse by immunohistochemistry and in situ hybridization. Results show that
      the two molecules are expressed in specific and restricted patterns in numerous
      brain nuclei, gray matter areas and cortical layers that are widely distributed
      throughout the mouse forebrain at postnatal day 1. The expression pattern of R
      cadherin is clearly distinct from that of N-cadherin, but overlap is observed in
      many areas. In many cortical areas, the two cadherins have a laminar-specific
      distribution that varies from region to region. In addition, immunohistochemical
      data revealed expression of R-cadherin protein and N-cadherin protein in the
      neuropil of many brain regions as well as in the axons that travel in fiber
      tracts such as the olfactory tract, the anterior commissure, the corpus callosum,
      the stria terminalis and the fornix. Often, subsets of axons within the same
      fiber tract differentially express R-cadherin and N-cadherin, with partial
      overlap of expression. The targets of the cadherin-immunoreactive fiber bundles
      often contain neuropil as well as cell bodies of neurons that also express the
      same type(s) of cadherin, suggesting that R-cadherin and N-cadherin may be
      involved in target recognition and the establishment of connections.
      Specifically, the expression of R-cadherin and N-cadherin is related to the
      maturation of thalamocortical sensory pathways, corticofugal pathways, and
      pathways associated with the hippocampal complex, the piriform cortex, and the
      amygdala. It is also related to the development of the cell groups associated
      with these pathways.Together, the results from the present study indicate the
      possibility that the selective adhesion of neural structures that express the
      same type(s) of cadherin contributes to the formation of gray matter areas,
      neural circuits and functional connections in the postnatal forebrain of the
      mouse.

PMID- 11591454
TI  - Individual differences in novelty-seeking behavior in rats: a c-fos study.
AB  - Novelty-seeking personality traits have been implicated in substance abuse and
      psychiatric disorders in humans. Novelty-seeking behaviors are also observed in
      rats, and individual rats exhibit substantial differences in expression of these
      behaviors. Thus, some rats exhibit low reactivity to novelty and high anxiety
      like behavior and are termed low responders, while others are hyperresponsive to
      novelty and exhibit low anxiety-like behavior and are termed high responders.
      While we and others had shown differences in patterns of gene expression in high
      and low responding animals at rest, no studies have described their brain
      activation following an anxiety test. We report here that a 5-min exposure to an
      anxiogenic stressor induced distinct patterns of c-fos expression in the brains
      of high and low responding rats. When compared to low responders, high responding
      rats showed low expression of c-fos mRNA in the CA1 area of the hippocampus, but
      high c-fos mRNA levels in the olfactory area, the orbital cortex, the cingulate
      cortex, the dorsal striatum and the paraventricular nucleus of the hypothalamus.
      Given that c-fos is a trans-acting factor, we suggest that the short- and long
      term consequences of the exposure to the anxiogenic stressor may also be
      quantitatively and anatomically different in these two groups of animals. Thus,
      these c-fos results demonstrate how experience may further exaggerate individual
      differences. Animals that differ in emotional reactivity not only exhibit basal
      differences in gene expression, but also react to novelty with different
      molecular responses, further increasing the neuronal differences between them.

PMID- 11591455
TI  - The selective 5-HT(1A) receptor agonist repinotan HCl attenuates histopathology
      and spatial learning deficits following traumatic brain injury in rats.
AB  - The selective 5-HT(1A) receptor agonist Repinotan HCl (BAY x3702) has been
      reported to attenuate cortical damage and improve functional performance in
      experimental models of cerebral ischemia and acute subdural hematoma. Using a
      clinically relevant contusion model of traumatic brain injury, we tested the
      hypothesis that a 4-h continuous infusion of Repinotan HCl (10 microg/kg/h i.v.)
      commencing 5 min post-injury would ameliorate functional outcome and attenuate
      histopathology. Forty isoflurane-anesthetized male adult rats were randomly
      assigned to receive either a controlled cortical impact (2.7 mm tissue
      deformation, 4 m/s) or sham injury (Injury/Vehicle=10, Injury/MK-801=10,
      Injury/Repinotan HCl=10, Sham/Vehicle=10), then tested for vestibulomotor
      function on post-operative days 1-5 and for spatial learning on days 14-18.
      Neither Repinotan HCl nor the non-competitive N-methyl-D-aspartate receptor
      antagonist MK-801, which served as a positive control, improved vestibulomotor
      function on beam balance and beam walk tasks relative to the Injury/Vehicle
      group, but both did significantly attenuate spatial learning and memory deficits
      on a water maze task. Repinotan HCl also reduced hippocampal CA(1) and CA(3)
      neuronal loss, as well as cortical tissue damage, compared to the Injury/Vehicle
      group at 4 weeks post-trauma. No significant difference in histological outcome
      was revealed between the Repinotan HCl- and MK-801-treated groups.These findings
      extend the therapeutic efficacy of Repinotan HCl to a contusion model of
      experimental brain injury and demonstrate for the first time that 5-HT(1A)
      receptor agonists confer neuroprotection and attenuate spatial learning deficits
      following controlled cortical impact injury. This treatment strategy may be
      beneficial in a clinical context where memory impairments are common following
      human traumatic brain injury.

PMID- 11591456
TI  - Altered expression of apolipoprotein E, amyloid precursor protein and presenilin
      1 is associated with chronic reactive gliosis in rat cortical tissue.
AB  - A major characteristic feature of Alzheimer's disease is the formation of
      compact, extracellular deposits of beta-amyloid (senile plaques). These deposits
      are surrounded by reactive astrocytes, microglia and dystrophic neurites.
      Mutations in three genes have been implicated in early-onset familial Alzheimer's
      disease. However, inflammatory changes and astrogliosis are also believed to play
      a role in Alzheimer's pathology. What is unclear is the extent to which these
      factors initiate or contribute to the disease progression. Previous rat studies
      demonstrated that heterotopic transplantation of foetal cortical tissue onto the
      midbrain of neonatal hosts resulted in sustained glial reactivity for many
      months. Similar changes were not seen in cortex-to-cortex grafts. Using this
      model of chronic cortical gliosis, we have now measured reactive changes in the
      levels of the key Alzheimer's disease proteins, namely the amyloid precursor
      protein, apolipoprotein E and presenilin-1. These changes were visualised
      immunohistochemically and were quantified by western blot analysis. We report
      here that chronic cortical gliosis in the rat results in a sustained increase in
      the levels of apolipoprotein E and total amyloid precursor protein. Reactive
      astrocytes in heterotopic cortical grafts were immunopositive for both of these
      proteins. Using a panel of amyloid precursor protein antibodies we demonstrate
      that chronic reactive gliosis is associated with alternative cleavage of the
      peptide. No significant changes in apolipoprotein E or amyloid precursor protein
      expression were seen in non-gliotic cortex-to-cortex transplants. Compared to
      host cortex, the levels of both N-terminal and C-terminal fragments of presenilin
      1 were significantly lower in gliotic heterotopic grafts.The changes described
      here largely mirror those seen in the cerebral cortex of humans with Alzheimer's
      disease and are consistent with the proposal that astrogliosis may be an
      important factor in the pathogenesis of this disease.

PMID- 11591457
TI  - Regulated expression of the neuronal calcium sensor-1 gene during long-term
      potentiation in the dentate gyrus in vivo.
AB  - Neuronal calcium sensor-1 (NCS-1), the mammalian homologue of frequenin, is a
      member of a highly conserved family of neuron-specific calcium-binding proteins
      which has been implicated in exocytosis and in multiple calcium-signalling
      pathways, suggesting a potential involvement in mechanisms of neuronal
      plasticity. Here, using in situ hybridization, we report an increased induction
      of the mRNA encoding NCS-1 in dentate granule cells following the induction of
      long-term potentiation in the awake rat. We show that NCS-1 mRNA levels are
      increased 1 and 3 h after long-term potentiation in an N-methyl-D-aspartate
      receptor-dependent manner, returning to baseline expression levels by 6 h.
      Electroconvulsive stimulation also induced NCS-1 mRNA transcription in the
      dentate gyrus, but at the different time of 6 h post-seizure, returning to
      baseline by 12 h. These results show that regulated expression of the NCS-1 gene
      is part of the transcriptional response associated with activity-dependent
      neuronal plasticity in vivo and suggest a molecular mechanism capable of
      mediating a functional change in synapse sensitivity to calcium and calcium
      signalling pathways after long-term potentiation.

PMID- 11591458
TI  - Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D
      aspartate responses in medium spiny striatal neurons.
AB  - Medium spiny neurons were recorded from striatal slices obtained from mice
      lacking the group I metabotropic glutamate receptor (mGluR) subtype 1 or subtype
      5. In wild-type animals, N-methyl-D-aspartate (NMDA)-induced membrane
      depolarization/inward currents were potentiated in the presence of both the group
      I mGluR agonist 3,5-dihydroxyphenylglycine (3,5-DHPG) and the mGluR5 selective
      agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG). Likewise, in mGluR1 knockout
      mice, both 3,5-DHPG and CHPG were able to potentiate NMDA responses. Conversely,
      in neurons recorded from mGluR5-deficient mice, the enhancement of NMDA responses
      by both 3,5-DHPG and CHPG was absent. Pharmacological analysis performed from rat
      slices confirmed the data obtained with mice. In the presence of the competitive
      mGluR1 antagonist LY367385, the NMDA responses were potentiated in the presence
      of CHPG, whereas the CHPG-induced enhancement was not observed in slices treated
      with the non-competitive mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine.
      As in wild-type mice, in neither of the mGluR1- and mGluR5-deficient mice did
      (2S,1'R,2'R,3'R)-2-(2,3-dicarboxylcyclopropyl)-glycine (1 microM), nor L-serine-O
      phosphate (30 microM) (agonists for group II and III mGluRs, respectively) affect
      the NMDA-evoked responses. In striatal medium spiny neurons, NMDA responses are
      potentiated by endogenous acetylcholine via M1-like muscarinic receptors. Since
      the enhancement of NMDA responses by 3,5-DHPG and by M1-like muscarinic agonists
      was shown to share common post-receptor mechanisms, we verified whether the
      muscarinic potentiation of NMDA responses was affected in these group I mGluR
      deficient mice. Both in mGluR1 and mGluR5 knockout animals, in the presence of
      either muscarine or the M1-like muscarinic receptor agonist McN-A-343, the
      positive modulation of the NMDA-induced membrane depolarization persisted.These
      results confirm the permissive role of group I mGluRs on NMDA responses in
      striatal neurons and reveal that this functional interplay occurs exclusively
      through the mGluR5 subtype. The NMDA-mGluR5 interaction might play an important
      modulatory role in the final excitatory drive from corticostriatal afferents and
      suggests that drugs acting at mGluR5 might prove useful for the treatment of
      movement disorders involving the striatum.

PMID- 11591459
TI  - Mouse model of Parkinsonism: a comparison between subacute MPTP and chronic
      MPTP/probenecid treatment.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is widely used to induce an
      animal model of Parkinsonism. The conventional mouse model, which usually
      involves acute or subacute injections of MPTP, results in a significant but
      reversible loss of dopaminergic functions. We have developed an alternative mouse
      model, in which co-administration of MPTP with probenecid results in the chronic
      loss of striatal dopamine for at least 6 months after cessation of treatment. In
      the present study, we compare the neurochemical, morphological and behavioral
      changes that occur in this alternative, chronic model with those in the
      conventional, subacute model. In the chronic model, we demonstrate an almost 80%
      loss of striatal dopamine and dopamine uptake 6 months after withdrawal from
      treatment. The neurochemical signs match unbiased stereological measures that
      demonstrate gradual loss of substantia nigra neurons. Rotarod performance further
      substantiates these findings by showing a progressive decline in motor
      performance. Based on the comparisons made in this study in mice, the chronic
      MPTP/probenecid model shows considerable improvements over the conventional,
      subacute MPTP model. The sustained alterations in the nigrostriatal pathway
      resemble the cardinal signs of human Parkinson's disease and suggest that this
      chronic mouse model is potentially useful to study the pathophysiology and
      mechanisms of Parkinsonism. It should also prove useful for the development of
      neuroprotection strategies.

PMID- 11591461
TI  - A gradient of plasticity in the amygdala revealed by cortical and subcortical
      stimulation, in vivo.
AB  - Projections to the amygdala from various cortical and subcortical areas terminate
      in different nuclei. In the present study we examined long-term potentiation of
      synaptic transmission in the lateral or the basal amygdaloid nuclei by theta
      burst stimulation of thalamic vs. cortical sensory projections in the
      anesthetized rat. Although both the medial geniculate nucleus and the dorsal
      perirhinal cortex have direct projections to lateral nucleus, only the thalamic
      stimulation induced long-term potentiation of field potentials recorded in the
      lateral nucleus. In contrast, cortical (ventral perirhinal cortex) but not
      thalamic stimulation induced long-term potentiation in the basal nucleus. Since
      the thalamic pathway is believed to process simple/unimodal stimulus features,
      and the perirhinal cortex complex/polymodal sensory representations, the
      dissociation of long-term potentiation in lateral and basal nuclei suggests that
      the basal nucleus may serve as an amygdaloid sensory interface for complex
      stimulus information similar to the role of the lateral nucleus in relation to
      relatively simple representations. Thus plasticity of simple and complex
      representations may involve different amygdala inputs and circuits.

PMID- 11591460
TI  - Lithium suppresses excitotoxicity-induced striatal lesions in a rat model of
      Huntington's disease.
AB  - Huntington's disease is a progressive, inherited neurodegenerative disorder
      characterized by the loss of subsets of neurons primarily in the striatum. In
      this study, we assessed the neuroprotective effect of lithium against striatal
      lesion formation in a rat model of Huntington's disease in which quinolinic acid
      was unilaterally infused into the striatum. For this purpose, we used a dopamine
      receptor autoradiography and glutamic acid decarboxylase mRNA in situ
      hybridization analysis, methods previously shown to be adequate for quantitative
      analysis of the excitotoxin-induced striatal lesion size. Here we demonstrated
      that subcutaneous injections of LiCl for 16 days prior to quinolinic acid
      infusion considerably reduced the size of quinolinic acid-induced striatal
      lesion. Furthermore, these lithium pre-treatments also decreased the number of
      striatal neurons labeled with the terminal deoxynucleotidyl transferase-mediated
      dUTP-biotin nick end labeling assay. Immunohistochemistry and western blotting
      demonstrated that lithium-elicited neuroprotection was associated with an
      increase in Bcl-2 protein levels. Our results raise the possibility that lithium
      may be considered as a neuroprotective agent in treatment of neurodegenerative
      diseases such as Huntington's disease.

PMID- 11591462
TI  - Immunoreactivity to P2X(6) receptors in the rat hypothalamo-neurohypophysial
      system: an ultrastructural study with extravidin and colloidal gold-silver
      labelling.
AB  - The distribution of the purine receptor P2X(6) subtype was studied in the rat
      hypothalamo-neurohypophysial system at the electron microscope level. Receptors
      were visualised with ExtrAvidin peroxidase conjugate and immunogold-silver pre
      embedding immunocytochemistry using a polyclonal antibody against an
      intracellular domain of the receptor. Application of ExtrAvidin labelling
      revealed P2X(6) receptors in subpopulations of: (i) neurosecretory cell bodies,
      neurosecretory and non-neurosecretory axons and dendrites of neurones in the
      paraventricular and supraoptic nuclei; and (ii) pituicytes and neurosecretory
      axons of the neurohypophysis. Some of the neurosecretory granules observed in the
      supraoptic and paraventricular nuclei neurone cell bodies, dendrites and axons as
      well as those in neurohypophysial axons were also positive for the P2X(6)
      receptors. In the paraventricular nucleus, some axons and dendrites of non
      neurosecretory neurones positive for P2X(6) receptors formed synapses between
      themselves. Using the immunogold-silver method, the electron-dense particles
      labelling P2X(6) receptors were found in neurosecretory cell bodies of the
      supraoptic and paraventricular nuclei, in relation to the cytoplasm, endoplasmic
      reticulum, Golgi complex and neurosecretory granules. The particles indicative of
      P2X(6) receptors were also located in neurosecretory and non-neurosecretory axons
      including axonal buttons making synapses with P2X(6)-negative dendrites. In the
      neurohypophysis, the electron-dense particles were localised in a subpopulation
      of pituicytes and neurosecretory axons. In neurohypophysial axons, particles were
      at times seen over the membrane of some neurosecretory granules (immunogold
      label) or microvesicles (immunoperoxidase label). We speculate that the P2X(6)
      receptors at the neurohypophysial level may be implicated not only in hormone
      release from the axon terminals, but also in membrane recycling of the granular
      vesicles and microvesicles.

PMID- 11591463
TI  - Intracranial self-stimulation induces Fos expression in GABAergic neurons in the
      rat mesopontine tegmentum.
AB  - The cholinergic neurons which originate in the mesopontine tegmentum and
      innervate the midbrain ventral tegmental area have been proposed to play a key
      role in intracranial self-stimulation reward. This mesopontine area also contains
      GABA neurons. Detailed information is still lacking, however, about the
      relationship of cholinergic and GABAergic neurons in this region to self
      stimulation reward. Therefore, using double immunostaining for Fos as a marker of
      neuronal activity and choline acetyltransferase as a marker of cholinergic
      neurons, or for Fos and GABA, we investigated whether self-stimulation of the
      medial forebrain bundle induces Fos expression within cholinergic and GABAergic
      neurons in two regions of the mesopontine tegmentum, i.e., pedunculopontine
      tegmental nucleus and laterodorsal tegmental nucleus. Self-stimulation of the
      medial forebrain bundle for 1 h induced a large increase in the number of cells
      expressing Fos in both the pedunculopontine tegmental nucleus and laterodorsal
      tegmental nucleus, when compared to control brains. However, the self-stimulation
      induced expression of Fos was restricted mostly to GABA-, but not choline
      acetyltransferase-, immunostained cells. We also examined, using microdialysis,
      whether self-stimulation increases acetylcholine efflux in the ventral tegmental
      area, a terminal region of the mesopontine tegmentum cholinergic pathway. One
      hour of self-stimulation significantly increased acetylcholine efflux from this
      terminal area. These results indicate that intracranial self-stimulation of the
      medial forebrain bundle may increase acetylcholine release without affecting
      expression of Fos in cholinergic neurons, while the same stimulation may induce
      Fos expression in GABAergic neurons of the mesopontine tegmentum. GABAergic as
      well as cholinergic neurons in this area appear to be activated by self
      stimulation reward in the medial forebrain bundle.

PMID- 11591464
TI  - Mechanothermal nociceptors in the scaly skin of the chicken leg.
AB  - Electrophysiological recordings were made from single sensory mechanothermal
      nociceptive afferent fibres in dissected nerve filaments of the parafibular nerve
      innervating the scaly skin of the lower leg of the chicken. Two classes of
      mechanothermal nociceptors were identified consisting of 34 C fibres (conduction
      velocities 0.45-1.5 m/s, mean 1.08) and nine A-delta fibres (3-15 m/s, mean
      6.34). The C fibre afferents had receptive fields which were circular or
      elliptical in shape and ranged in size from 1 mm in diameter to 4 x 3 mm.
      Thresholds to mechanical stimulation in the C fibre afferents ranged from 0.3 to
      33 g (median 1.5 g) and thermal thresholds were in the range 39-61 degrees C
      (median 49.4 degrees C). Stimulus-response curves to thermal and/or mechanical
      stimulation were recorded from 28 C fibre afferents and subjected to a linear
      regression analysis to determine whether they were best fitted by a linear, log
      or power function. The results were variable and no single function provided the
      best fit for all the responses. Of the fibres tested with both stimulus
      modalities (n=17), only 12 fibres showed the same best fit for both stimuli; in
      the others the best fit regression lines differed between stimuli. The response
      of the A-delta fibres to mechanical and thermal stimulation was very similar to
      the C fibres but the small number of A-delta fibres precluded any detailed
      statistical analysis. Comparison of the physiological properties of the C fibres
      in the leg with those previously identified in the beak showed that those in the
      leg had significantly lower thermal thresholds, but higher mechanical thresholds.
      The possible functional significance of these differences is discussed. These
      findings are also discussed in a comparative context to identify similarities and
      differences between mechanothermal nociceptors in birds and other vertebrates,
      relating these to their possible evolutionary and functional significance.

PMID- 11591466
TI  - Misunderstandings about isochores. Part 1.
AB  - A few months ago the International Human Genome Sequencing Consortium (IHGSC)
      published a 61-page paper on the human genome (IHGSC, Nature 409 (2001) 860).
      Here comments will be presented on some points of the paper that were previously
      investigated in our laboratory, and some misunderstandings and misconceptions
      about the organization and the evolutionary history of the human genome will be
      discussed. A very recent article on the same subject (Eyre-Walker and Hurst, Nat.
      Rev. Genet. 2 (2001) 549) will also be addressed. The present paper is a
      complement to two review articles which were published last year (Bernardi, Gene
      241 (2000) 3; Gene 259(1) (2000) 31).

PMID- 11591467
TI  - Compositional heterogeneity within and among isochores in mammalian genomes. I.
      CsCl and sequence analyses.
AB  - GC level distributions of a species' nuclear genome, or of its compositional
      fractions, encode key information on structural and functional properties of the
      genome and on its evolution. They can be calculated either from absorbance
      profiles of the DNA in CsCl density gradients at sedimentation equilibrium, or by
      scanning long contigs of largely sequenced genomes. In the present study, we
      address the quantitative characterization of the compositional heterogeneity of
      genomes, as measured by the GC distributions of fixed-length fragments. Special
      attention is given to mammalian genomes, since their compartmentalization into
      isochores implies two levels of heterogeneity, intra-isochore (local) and inter
      isochore (global). This partitioning is a natural one, since large-scale
      compositional properties vary much more among isochores than within them. Intra
      isochore GC distributions become roughly Gaussian for long fragments, and their
      standard deviations decrease only slowly with increasing fragment length, unlike
      random sequences. This effect can be explained by 'long-range' correlations,
      often overlooked, that are present along isochores.

PMID- 11591468
TI  - Compositional heterogeneity within and among isochores in mammalian genomes. II.
      Some general comments.
AB  - The presence of long-range correlations and/or mosaicism in DNA sequences results
      in GC fluctuations, even within individual isochores that are much larger than
      expected correlation-free 'random' sequences. Neglecting the presence of such
      fluctuations can lead to incorrect conclusions regarding relative homogeneity or
      isochore borders. In this commentary, we address these and other methodological
      issues raised by the variations in GC level within human isochores. We also
      discuss some recent misconceptions.

PMID- 11591469
TI  - Standard deviations and correlations of GC levels in DNA sequences.
AB  - In a DNA sequence that exhibits long-range correlations, standard deviations
      among the GC levels of its segments can be up to an order of magnitude higher
      than in a sequence consisting of independent, identically distributed
      nucleotides. Conversely, plots of inter-segment standard deviations vs. segment
      length reveal quantitative information about the correlations present in a
      sequence. We present and discuss formulae that relate long-range (power-law)
      correlations between the nucleotides of a sequence to the expected standard
      deviations of the GC levels of its segments, and to the correlations between
      them.

PMID- 11591470
TI  - Similar integration but different stability of Alus and LINEs in the human
      genome.
AB  - Alus and LINEs (LINE1) are widespread classes of repeats that are very unevenly
      distributed in the human genome. The majority of GC-poor LINEs reside in the GC
      poor isochores whereas GC-rich Alus are mostly present in GC-rich isochores. The
      discovery that LINES and Alus share similar target site duplication and a common
      AT-rich insertion site specificity raised the question as to why these two
      families of repeats show such a different distribution in the genome. This
      problem was investigated here by studying the isochore distributions of
      subfamilies of LINES and Alus characterized by different degrees of divergence
      from the consensus sequences, and of Alus, LINEs and pseudogenes located on
      chromosomes 21 and 22. Young Alus are more frequent in the GC-poor part of the
      genome than old Alus. This suggests that the gradual accumulation of Alus in GC
      rich isochores has occurred because of their higher stability in compositionally
      matching chromosomal regions. Densities of Alus and LINEs increase and decrease,
      respectively, with increasing GC levels, except for the telomeric regions of the
      analyzed chromosomes. In addition to LINEs, processed pseudogenes are also more
      frequent in GC-poor isochores. Finally, the present results on Alu and LINE
      stability/exclusion predict significant losses of Alu DNA from the GC-poor
      isochores during evolution, a phenomenon apparently due to negative selection
      against sequences that differ from the isochore composition.

PMID- 11591471
TI  - Isochore chromosome maps of eukaryotic genomes.
AB  - Analytical DNA ultracentrifugation revealed that eukaryotic genomes are mosaics
      of isochores: long DNA segments (>>300 kb on average) relatively homogeneous in
      G+C. Important genome features are dependent on this isochore structure, e.g.
      genes are found predominantly in the GC-richest isochore classes. However, no
      reliable method is available to rigorously partition the genome sequence into
      relatively homogeneous regions of different composition, thereby revealing the
      isochore structure of chromosomes at the sequence level. Homogeneous regions are
      currently ascertained by plain statistics on moving windows of arbitrary length,
      or simply by eye on G+C plots. On the contrary, the entropic segmentation method
      is able to divide a DNA sequence into relatively homogeneous, statistically
      significant domains. An early version of this algorithm only produced domains
      having an average length far below the typical isochore size. Here we show that
      an improved segmentation method, specifically intended to determine the most
      statistically significant partition of the sequence at each scale, is able to
      identify the boundaries between long homogeneous genome regions displaying the
      typical features of isochores. The algorithm precisely locates classes II and III
      of the human major histocompatibility complex region, two well-characterized
      isochores at the sequence level, the boundary between them being the first
      isochore boundary experimentally characterized at the sequence level. The
      analysis is then extended to a collection of human large contigs. The relatively
      homogeneous regions we find show many of the features (G+C range, relative
      proportion of isochore classes, size distribution, and relationship with gene
      density) of the isochores identified through DNA centrifugation. Isochore
      chromosome maps, with many potential applications in genomics, are then drawn for
      all the completely sequenced eukaryotic genomes available.

PMID- 11591472
TI  - Delineating relative homogeneous G+C domains in DNA sequences.
AB  - The concept of homogeneity of G+C content is always relative and subjective. This
      point is emphasized and quantified in this paper using a simple example of one
      sequence segmented into two subsequences. Whether the sequence is homogeneous or
      not can be answered by whether the two-subsequence model describes the DNA
      sequence better than the one-sequence model. There are at least three equivalent
      ways of looking at the 1-to-2 segmentation: Jensen-Shannon divergence measure,
      log likelihood ratio test, and model selection using Bayesian information
      criterion. Once a criterion is chosen, a DNA sequence can be recursively
      segmented into multiple domains. We use one subjective criterion called
      segmentation strength based on the Bayesian information criterion. Whether or not
      a sequence is homogeneous and how many domains it has depend on this criterion.
      We compare six different genome sequences (yeast S. cerevisiae chromosome III and
      IV, bacterium M. pneumoniae, human major histocompatibility complex sequence,
      longest contigs in human chromosome 21 and 22) by recursive segmentations at
      different strength criteria. Results by recursive segmentation confirm that yeast
      chromosome IV is more homogeneous than yeast chromosome III, human chromosome 21
      is more homogeneous than human chromosome 22, and bacterial genomes may not be
      homogeneous due to short segments with distinct base compositions. The recursive
      segmentation also provides a quantitative criterion for identifying isochores in
      human sequences. Some features of our recursive segmentation, such as the
      possibility of delineating domain borders accurately, are superior to those of
      the moving-window approach commonly used in such analyses.

PMID- 11591473
TI  - Structural and functional features of eukaryotic mRNA untranslated regions.
AB  - The crucial role of the non-coding portion of genomes is now widely acknowledged.
      In particular, mRNA untranslated regions are involved in many post
      transcriptional regulatory pathways that control mRNA localization, stability and
      translation efficiency. We review in this paper the major structural and
      compositional features of eukaryotic mRNA untranslated regions and provide some
      examples of bioinformatic analyses for their functional characterization.

PMID- 11591474
TI  - Positively selected amino acid sites in the entire coding region of hepatitis C
      virus subtype 1b.
AB  - To predict the amino acid sites important for the clearance of hepatitis C virus
      (HCV) subtype 1b in vivo, positively selected amino acid sites were detected by
      analyzing the sequence data collected from the international DNA databank. The
      rate of nonsynonymous substitutions per nonsynonymous site was compared with that
      of synonymous substitutions per synonymous site for each codon site in the entire
      coding region. As a result, 13 out of 3010 amino acid sites were found to be
      positively selected. Among the 13 positively selected amino acid sites, eight
      were located in the structural proteins and five were in the nonstructural
      proteins. Moreover, eight were located in B-cell epitopes and two were in T-cell
      epitopes. These observations suggest that both the antibody and the cytotoxic T
      lymphocyte are involved in the clearance of HCV subtype 1b in vivo. These
      positively selected amino acid sites represent candidate vaccination targets for
      HCV subtype 1b.

PMID- 11591475
TI  - Analysis of codon usage diversity of bacterial genes with a self-organizing map
      (SOM): characterization of horizontally transferred genes with emphasis on the E.
      coli O157 genome.
AB  - With increases in the amounts of available DNA sequence data, it has become
      increasingly important to develop tools for comprehensive systematic analysis and
      comparison of species-specific characteristics of protein-coding sequences for a
      wide variety of genomes. In the present study, we used a novel neural-network
      algorithm, a self-organizing map (SOM), to efficiently and comprehensively
      analyze codon usage in approximately 60,000 genes from 29 bacterial species
      simultaneously. This SOM makes it possible to cluster and visualize genes of
      individual species separately at a much higher resolution than can be obtained
      with principal component analysis. The organization of the SOM can be explained
      by the genome G+C% and tRNA compositions of the individual species. We used SOM
      to examine codon usage heterogeneity in the E. coli O157 genome, which contains
      'O157-unique segments' (O-islands), and showed that SOM is a powerful tool for
      characterization of horizontally transferred genes.

PMID- 11591476
TI  - Correlation between sequence conservation of the 5' untranslated region and codon
      usage bias in Mus musculus genes.
AB  - The codon adaptation index (CAI) values of all protein-coding sequences of the
      full-length cDNA libraries of Mus musculus were computed based on the RIKEN mouse
      full-length cDNA library. We have also computed the extent of consensus in
      flanking sequences of the initiator ATG codon based on the 'relative entropy'
      values of respective nucleotide positions (from -20 to +12 bp relative to the
      initiator ATG codon) for each group of genes classified by CAI values. With
      regard to the two nucleotides positions (-3 and +4) known to be highly conserved
      in Kozak's consensus sequence, a clear correlation between CAI values and
      relative entropy values was observed at position -3 but this was not significant
      at position +4, although a significant correlation was found at position -1 of
      the consensus sequence. Further, although no correlation was observed at any
      additional positions, relative entropy values were very high at positions -4, -6,
      and -8 in genes with high CAI values. These findings suggest that the extent of
      conservation in the flanking sequence of the initiator ATG codon including
      Kozak's consensus sequence was an important factor in modulation of the
      translation efficiency as well as synonymous codon usage bias particularly in
      highly expressed genes.

PMID- 11591477
TI  - Preferential usage of some minor codons in bacteria.
AB  - In many bacterial species, such as Deinococcus radiodurans, Haemophilus
      influenzae, and Methanobacterium thermoautotrophicum, some minor codons are
      preferentially used near the initiation codon. Among these codons, there are some
      minor codons that have strong preference for the initiation site in the high
      codon adaptation index (CAI) group (comprising of highly expressed genes) rather
      than in the low CAI genes group (comprising of low expressing genes). In the
      present study, codon usage in the initiation site and in the rest of the gene was
      systematically compared in the 27 complete bacterial genomes and Saccharomyces
      cerevisiae genome. Furthermore, we classified genes into two groups according to
      the CAI values and conducted the same analysis for each of the two groups. Our
      results suggest a role for some minor codons in the initiation site of the
      regulating translation system in many bacteria. We have summarized codons that
      are preferentially used in the initiation site and probably play a role in
      regulating genes expression in these organisms.

PMID- 11591478
TI  - Molecular evolution of the cone visual pigments in the pure rod-retina of the
      nocturnal gecko, Gekko gekko.
AB  - We have isolated a full-length cDNA encoding a putative ultraviolet (UV)
      sensitive visual pigment of the Tokay gecko (Gekko gekko). This clone has 57 and
      59% sequence similarities to the gecko RH2 and MWS pigment genes, respectively,
      but it shows 87% similarity to the UV pigment gene of the American chameleon
      (Anolis carolinensis). The evolutionary rates of amino acid replacement are
      significantly higher in the three gecko pigments than in the corresponding
      chameleon pigments. The accelerated evolutionary rates reflect not only the
      transition from cones to rods in the retina but also the blue-shift in the
      absorption spectra of the gecko pigments.

PMID- 11591479
TI  - Genome-wide chromatin remodeling modulates the Alu heat shock response.
AB  - During heat shock recovery in Hela cells, the level of Alu RNA transiently
      increases with kinetics that approximately parallel the transient expression of
      heat shock protein mRNAs. Coincidentally, there is a transient increase in the
      accessibility of Alu chromatin to restriction enzyme cleavage suggesting that an
      opening and re-closing of chromatin regulates the Alu stress response. Similar
      changes occur in alpha satellite and LINE1 chromatin showing that heat shock
      induces a genome-wide remodeling of chromatin structure which is independent of
      transcription. The increased accessibility of restriction sites within these
      repetitive sequences is inconsistent with a simple lengthening of the nucleosome
      linker region but instead suggests a scrambling of nucleosome positions.
      Chromatin structure and its dynamics account for many of the principal features
      of SINE transcriptional regulation potentially providing a functional rationale
      for the dispersion and high copy number of SINEs.

PMID- 11591480
TI  - Differential stress induction of individual Alu loci: implications for
      transcription and retrotransposition.
AB  - While human Alu repeats can be considered to be members of an extremely large,
      globally regulated, multigene family, each member of this family resides within a
      different sequence context that might uniquely modulate its transcription. Unique
      3' flanking sequences for several transcriptionally active human Alu elements
      were identified by cDNA cloning and used for primer extension analysis to compare
      the basal and stress-induced expression of the corresponding Alu loci. Each of
      six Alu loci investigated exhibits a unique pattern of expression in three
      different human cell lines and in response to stress induction. The sequence
      context surrounding each Alu member uniquely determines its transcriptional
      regulation. In many cases, the individual Alu loci and total Alu RNA exhibit
      opposing patterns of expression implying that local rather than global regulation
      ultimately determines the expression of individual members. Some of the stresses,
      which induce Alu transcription, increase co-expression of LINE1 RNA, another
      requirement for Alu retrotransposition.

PMID- 11591481
TI  - Within-intron correlation with base composition of adjacent exons in different
      genomes.
AB  - Within-intron difference of correlation with base composition of the adjacent
      exons was studied in the genomes of 34 species. For this purpose, GC-percent was
      determined for segments of 50 bp in length taken at both intron margins and in
      the internal part of the intron. It was found that in certain genomes the
      coefficient of correlation with GC-percent of the adjacent exon was significantly
      higher for the intron margin than for the internal part of the intron
      (homeotherms, cereals). Only part of this difference can be explained by unequal
      probability of insertion of transposable elements. Those multicellular organisms
      which have a low or no within-intron difference in correlation with the adjacent
      exons (anamniotes, invertebrates, dicots) show a higher local compositional
      heterogeneity (a greater exon/intron contrast in the GC-content). These results
      are evidence against the mutational bias being a possible explanation for the
      compositional genome heterogeneity. Thus, in the genomes with a high global
      heterogeneity there seems to be a selective force for compliance of intron base
      composition with the adjacent exons. This force is stronger in those parts of the
      intron that are closer to exons. In addition, the previously found positive
      general correlation between the genome size and average intron length was
      confirmed with a much larger dataset. However, within separate phylogenetic
      groups this rule can be broken, as it occurs in the cereals (family Poaceae),
      where a negative correlation was found.

PMID- 11591482
TI  - A model for the involvement of Okazaki fragments maturation in the expansion of
      short tandem repeats.
AB  - We propose a model for the expansion of short tandem repeats (ESTR), a phenomenon
      which has been found to occur in human DNA and is associated with a dozen of
      neuromuscular diseases. The model is based mainly on theoretical considerations
      and recovers experimental data from the literature; it also finds support in
      preliminary results obtained by us in multiprimed polymerase chain reactions
      designed to assess the effects of a downstream primer on the fidelity of the
      elongation of an upstream one. The model links the occurrence of the ESTR to a
      defective maturation of the Okazaki fragments (OF), and in particular to an
      improper processing of their 3' termini. This may occur when the last OF
      approaches the 5' terminus of the previous one in a susceptible region of the
      template. It is postulated here that when a growing OF has progressed past the
      priming region and its main portion has been synthesized, upon approaching its
      conclusion, the final elongation may take place in a region of the template where
      certain triplets are repeated: in that case a series of aberrations on the
      elongation mechanism may occur. These aberrations could involve (a) the
      displacement of the 5' terminus of the penultimate, properly matured OF, enacted
      by the incoming 3' terminus of the last OF, (b) the switch of the latter to the
      displaced strand of the former as template, (c) the fold-back on itself of the
      growing 3' terminus of the last OF, (d) its assumption of an unusual structure
      because of the repetition, and (e) some impairment of its removal by structure
      specific exo-endonuclease(s). Derangements of this last part of the process may
      trigger the ESTR.

PMID- 11591483
TI  - Contribution of sponge genes to unravel the genome of the hypothetical ancestor
      of Metazoa (Urmetazoa).
AB  - Recently the term Urmetazoa, as the hypothetical metazoan ancestor, was
      introduced to highlight the finding that all metazoan phyla including the
      Porifera (sponges) are derived from one common ancestor. Sponges as the
      evolutionarily oldest, still extant phylum, are provided with a complex network
      of structural and functional molecules. Analyses of sponge genomes from
      Demospongiae (Suberites domuncula and Geodia cydonium), Calcarea (Sycon raphanus)
      and Hexactinellida (Aphrocallistes vastus) have contributed also to the
      reconstruction of the evolutionary position of Metazoa with respect to Fungi.
      Furthermore, these analyses have provided evidence that the characteristic
      evolutionary novelties of Metazoa, such as the extracellular matrix molecules,
      the cell surface receptors, the nervous signal transduction molecules as well as
      the immune molecule existing in Porifera, share high sequence and in some aspects
      also functional similarities to related polypeptides found in other metazoan
      phyla. During the transition to Metazoa new domains occurred; as one example, the
      formation of the death domain from the ankyrin is outlined. In parallel, domanial
      proteins have been formed, such as the receptor tyrosine kinases. The metazoan
      essentials have been defined by analyzing and comparing the sponge sequences with
      the related sequences from the metazoans Homo sapiens, Caenorhabditis elegans and
      Drosophila melanogaster, the fungus Saccharomyces cerevisiae and the plant
      Arabidopsis thaliana. The data revealed that those sponge molecules grouped to
      cell adhesion cell recognition proteins are predominantly found in Protostomia
      and Deuterostomia while they are missing in Fungi and Viridiplantae. Moreover,
      evidence is presented allowing the conclusion that the sponge molecules are more
      closely related to the corresponding molecules from H. sapiens than to those of
      C. elegans or D. melanogaster. Especially surprising was the finding that the
      Demospongiae are provided with elements of adaptive immunity.

PMID- 11591484
TI  - Immunolocalization of ClC-K chloride channel in strial marginal cells and
      vestibular dark cells.
AB  - Secretion of K(+) into endolymph depends on a particular constellation of ion
      transport proteins in the apical and basolateral membranes of strial marginal
      cells and vestibular dark cells. One fundamental component is the large chloride
      conductance of the basolateral membrane, which recycles chloride taken up by the
      Na(+)-K(+)-Cl(-) cotransporter in the same membrane. Evidence has been reported
      recently that supports ClC-K, a channel subunit previously thought to be specific
      to the kidney, as being the molecular entity underlying this conductance. We have
      isolated protein from the gerbil kidney, stria vascularis and vestibular
      labyrinth and found by Western blot analysis a 60 kDa band, a 48 kDa band and 54
      and 70 kDa bands, respectively, specifically labeled by ClC-K antibody.
      Subsequent immunohistochemical observations of the inner ear tissues with a
      confocal microscope on fluorescently labeled tissue sections showed the staining
      to be restricted to the basolateral region of strial marginal cells and
      vestibular dark cells. The cochlear staining was distinct from the distribution
      of the Kir4.1 (KCNJ10) K(+) channel, known to be present only in strial
      intermediate cells. These findings support the contention that ClC-K is an
      important component of the basolateral Cl(-) conductance that participates in
      K(+) secretion by these epithelia.

PMID- 11591485
TI  - Expression of midkine in the cochlea.
AB  - Midkine (MK) is one of a new family of heparin-binding growth factors involved in
      the regulation of growth and differentiation. We have analyzed expression of MK
      in the cochlea using ICR mice within 1 day from birth. The expression of MK in
      the cochlea was confirmed by Western blotting and immunohistochemistry. Anti-MK
      immunoreactivity was observed in the stria vascularis, spiral prominence, spiral
      ganglion, and ganglion nerve fibers. These findings suggest that MK plays a role
      in the development of the cochlea.

PMID- 11591486
TI  - Connexin 26 in human fetal development of the inner ear.
AB  - Specialized for intercellular communication, gap junctions have been theorized to
      provide a means (the epithelial and connective tissue gap junction systems) by
      which fluid and ions might be transported for maintenance of high levels of
      endolymphatic K+ [Kikuchi et al., 1994. Acta Otolaryngol. 114, 520-528] in the
      inner ear. A primary constituent of these gap junctions is connexin 26 (Cx26), a
      protein encoded by the gene GJB2 and found in both epithelial and connective
      tissue cells. It has been shown that a mutation in Cx26 accounts for 50% of
      patients with autosomal recessive nonsyndromic hearing loss. In the present
      study, we document the emergence and distribution features of Cx26 through
      various stages (weeks 11-31) of gestation in human, fetal cochleae. Comparative
      patterns of Cx26 distribution are also presented in the mature rat. The cochleae
      were fixed in 4% paraformaldehyde within 2 h post mortem. Immunohistochemical
      studies were performed using a rabbit polyclonal antibody raised against
      synthetic peptide and corresponding with amino acids 108-122. Specimens were
      mounted into paraffin sections. Results show that Cx26-like immunoreactivity is
      evident at a prenatal age of 11 weeks and maintains a high intensity of
      reactivity through 31 weeks of gestation. The appearance of this reactivity
      seemed to modulate in parallel with the onset of development and histological
      maturation as well as provide functional maintenance. In the human fetal cochlea,
      Cx26-like immunoreactivity distribution resembled adult patterns by fetal week
      20. At the completion of morphological development by week 31, reactivity
      appeared to achieve an adult profile of distribution. Descriptions and discussion
      of Cx26 distribution patterns are presented in detail.

PMID- 11591487
TI  - Effects of surgery and other experimental factors on the evaluation of middle ear
      function in gekkonoid lizards.
AB  - This study examines three artificial factors likely to cause variation between
      results from different investigations of auditory function, at least in lizards.
      Controlled tests were performed on gecko lizards, by external laser
      interferometry of the middle ear transfer function at the tympanic membrane (TM).
      In conclusion, studies of middle ear function should examine motion both at the
      insertion of the columella-extracolumella shaft onto the TM, and at the tip of
      the extracolumellar pars inferior, because the internal proportions and function
      of the extracolumellar lever vary among species. At least in scansorial geckos,
      auditory experiments may be conducted with the animal on its back, as this
      posture introduces no acoustic artifacts. Positioning the subject on its belly,
      with the throat resting on the substrate, imposes small but significant artifacts
      on middle ear function. Similar artifacts occur with the belly up but the throat
      loaded with a modeling clay plate. The surgical fenestration of the ventral
      throat wall, common in auditory studies on lizards, causes (at least in
      Eublepharis) artificial enhancement of sensitivity at low frequencies and erratic
      responses at high frequencies.

PMID- 11591488
TI  - Ischemia-reperfusion injury of the cochlea: effects of an iron chelator and
      nitric oxide synthase inhibitors.
AB  - Release of free iron from cellular stores and activation of nitric oxide synthase
      (NOS) has been implicated in a wide variety of cochlear injuries. In order to
      evaluate the effects of deferoxamine (a iron chelator), 3-bromo-7-nitroindazole
      (a relatively selective neuronal NOS (nNOS) inhibitor) or aminoguanidine (a
      relatively selective inducible NOS (iNOS) inhibitor) on the post-ischemic
      cochlear dysfunction, albino guinea pigs were subjected to 30 min ischemia, and
      the threshold shifts of the compound action potential (CAP) from pre-ischemic
      values were compared with those of control animals 4 h after the onset of
      reperfusion. A statistically significant reduction in the post-ischemic CAP
      threshold shift was observed in the animals treated with deferoxamine or 3-bromo
      7-nitroindazole. However, aminoguanidine did not affect the post-ischemic CAP
      threshold shift. These results suggest that free iron and nNOS play deleterious
      roles in the cochlear injury induced by transient ischemia.

PMID- 11591489
TI  - Na,K-ATPase expression in the mouse cochlea is not dependent on the
      mineralocorticoid receptor.
AB  - This study was performed in order to test the hypothesis that the
      mineralocorticoid hormone stimulates the expression of Na,K-ATPase in the cochlea
      of the mouse. Immunohistochemistry was used to investigate the distribution of
      the mineralocorticoid receptor (MR) in the cochlea of the C57Bl/J6 mouse at
      different ages between gestational day 19 and postnatal day 30, and the
      occurrence and distribution of Na,K-ATPase in the inner ear of a mouse with a
      null mutation of the MR. Adult patterns of staining for MR were found as early as
      on gestational day 19 in the cochlea, with small changes thereafter. MR was
      detected in the same structures in the cochlea as Na,K-ATPase in earlier studies,
      where the amount of Na,K-ATPase increased after postnatal day 4. Thus there is
      latency between the increase of MR and the increase of Na,K-ATPase. In the
      cochlea of the MR deficient mouse, antibody labelling of Na,K-ATPase showed no
      significant difference as compared to the control wild type mouse. The hypothesis
      that mineralocorticoid hormone alone via MR stimulates the formation of Na,K
      ATPase in the inner ear could not be confirmed by this study, and other
      regulating mechanisms must be considered.

PMID- 11591490
TI  - Spectrotemporal sensitivities in rat auditory cortical neurons.
AB  - Studies in several mammalian species have demonstrated that auditory cortical
      neurons respond strongly to single frequency-modulated (FM) sweeps, and that most
      responses are selective for sweep direction and/or rate. In the present study, we
      used extracellular recordings to examine how neurons in the auditory cortices of
      anesthetized rats respond to continuous, periodic trains of FM sweeps (described
      previously by deCharms et al., Science 280 (1998) pp. 1439-1444, as moving
      auditory gratings). Consistent with previous observations in owl monkeys, we
      found that the majority of cortical neurons responded selectively to trains of
      either up-sweeps or down-sweeps; selectivity for down-sweeps was most common.
      Periodic responses were typically evoked only by sweep trains with repetition
      rates less than 12 sweeps per second. Directional differences in responses were
      dependent on repetition rate. Our results support the proposal that a combination
      of both spectral and temporal acoustic features determines the responses of
      auditory cortical neurons to sound, and add to the growing body of evidence
      indicating that the traditional view of the auditory cortex as a frequency
      analyzer is not sufficient to explain how the mammalian brain represents complex
      sounds.

PMID- 11591491
TI  - Frequency sensitivity range of the saccule to bone-conducted stimuli measured by
      vestibular evoked myogenic potentials.
AB  - Vestibular evoked myogenic potentials (VEMPs) occurring in cervical muscles after
      intense sound stimulation conducted by air or bone are thought to be a
      polysynaptic response of otolith-vestibular nerve origin. We report the results
      of an experiment to investigate whether acoustic stimulation of the saccule by
      bone conduction produces VEMPs in which response amplitudes are somewhat
      sensitive to stimulus frequency, as appears to be the case with air-conducted
      stimuli. Prior to this we investigated the effect of stimulation repetition rate
      on bone-conducted VEMPs (B-VEMPs) at stimulus frequencies of 200 and 400 Hz with
      five different repetition rates (5, 10, 20, 40, and 80 Hz). B-VEMPs were recorded
      from 12 normal hearing subjects in response to bone-conducted 70 dB (normal
      hearing level), 10-ms tone bursts (rise/fall time=1 ms and plateau time=8 ms) at
      frequencies of 100, 200, 400, 800, 1600 and 3200 Hz. Our study showed that B-VEMP
      amplitudes were highest at 10 Hz but decreased as the repetition rate increased.
      B-VEMP response amplitudes were found to be maximal for stimulus frequencies from
      200 to 400 Hz. This response may contribute to the perception of loud sounds.

PMID- 11591492
TI  - Analysis of elastic properties of outer hair cell wall using shell theory(1).
AB  - In this study, the mechanical properties of the lateral wall of the outer hair
      cell (OHC) are determined theoretically. First, the cell is modeled as a
      cylindrical two-layer shell consisting of the plasma membrane and the cortical
      lattice. When the stiffness of the plasma membrane is set to be 1.0 mN/m based on
      the estimated value of Tolomeo et al. [Biophys. J. 71 (1996) 421-429], and
      Poisson's ratio of the plasma membrane is assumed to be 0.90, the relationships
      between the stiffness, Poisson's ratio and the orthotropism of the cortical
      lattice are obtained by comparing the measurement results of cell inflation by
      Iwasa and Chadwick [J. Acoust. Soc. Am. 92 (1992) 3169-3173] with the numerical
      ones obtained with our model. Next, the obtained relationships between these
      mechanical properties of the cell are applied to the model, and the result of the
      cell length change due to the axial compression measured by Hallworth [J.
      Neurophysiol. 74 (1995) 2319-2329] is compared with that obtained from our
      numerical analysis. As a result, the axial and circumferential stiffnesses of the
      cortical lattice are evaluated to be 4.6 mN/m and 13 mN/m, respectively. Then,
      the contribution of the cortical lattice to the stiffness of the OHC lateral wall
      is examined. When the stiffness of the plasma membrane is less than 1.0 mN/m, the
      mechanical properties of the cortical lattice obtained from the two-layer shell
      model are nearly the same as those of the cell lateral wall obtained from the one
      layer orthotropic shell model. Therefore, it is concluded that the stiffness of
      the cortical lattice is responsible for that of the whole lateral wall of the
      OHC. Moreover, the mechanical properties of the OHC obtained in this study are
      compared with those reported previously, and it is suggested that the one-layer
      orthotropic shell model is sufficient for further analyses of the motility and
      force production of the OHC.

PMID- 11591493
TI  - Acute effect of nicotine on non-smokers: I. OAEs and ABRs.
AB  - This paper is the first in a series of three investigating the role of
      cholinergic mechanisms in the auditory system by assessing the acute effects of
      nicotine, an acetylcholinomimetic drug, on aggregate responses within the
      auditory pathway. In a single-blind procedure, auditory responses were obtained
      from 20 normal-hearing, non-smokers (10 male) under two conditions (nicotine,
      placebo). After the drug session, plasma tests revealed a subject's nicotine
      concentration. The effects of nicotine on early, exogenous responses of the
      auditory system (otoacoustic emissions and auditory brainstem potentials) are
      described in this first paper. Results indicated that transdermal administration
      of nicotine to non-smokers does not significantly affect cochlear activity but
      does acutely affect the neural transmission of acoustic information. Overall,
      otoacoustic emissions were unaffected by transdermal nicotine while wave I of the
      auditory brainstem response was significantly increased in latency and decreased
      in amplitude.

PMID- 11591494
TI  - Acute effect of nicotine on non-smokers: II. MLRs and 40-Hz responses.
AB  - This paper is the second in a series of three investigating the role of
      cholinergic mechanisms in the auditory system by assessing the acute effects of
      nicotine, an acetylcholinomimetic drug, on aggregate responses within the
      auditory pathway. In a single-blind procedure, auditory responses were obtained
      from 20 normal-hearing, non-smokers (10 male) under two conditions (nicotine,
      placebo). The effects of nicotine on central, mesogenous responses of the
      auditory system (middle latency and 40-Hz responses) are described in this second
      paper. Results indicated that transdermal administration of nicotine to non
      smokers does significantly affect the central, neural transmission of acoustic
      information. Na-Pa amplitude and Nb latency of the middle latency response and
      latency measures of the 40-Hz response were acutely altered by the presence of
      nicotine.

PMID- 11591495
TI  - Acute effect of nicotine on non-smokers: III. LLRs and EEGs.
AB  - This paper is the last in a series of three investigating the role of cholinergic
      mechanisms in the auditory system by assessing the acute effects of nicotine, an
      acetylcholinomimetic drug, on aggregate responses within the auditory pathway. In
      a single-blind procedure, auditory responses were obtained from 20 normal
      hearing, non-smokers (10 male) under two conditions (nicotine, placebo). The
      effects of nicotine on long-latency responses of the auditory system and on
      electroencephalograms are described in this paper. Results indicated that
      transdermal administration of nicotine to non-smokers significantly affects the
      afferent and efferent transmission of acoustic information, as well as enhancing
      cortical activation. Long-latency response amplitudes and electroencephalogram
      activity (dominant power and frequencies) were altered by acute doses of
      transdermal nicotine.

PMID- 11591496
TI  - The latency of auditory nerve brainstem evoked responses to air- and bone
      conducted stimuli.
AB  - The auditory nerve brainstem evoked responses (ABRs) to bone conduction (BC)
      stimuli are longer in latency than those to air conduction (AC). In order to
      study the mechanism of this difference, ABR wave I was recorded in experimental
      animals in response to low intensity (0-20 dB above their threshold) logon
      stimuli delivered by BC and by using the same bone vibrator to generate the air
      conducted stimulus. The BC stimuli were delivered to skull bone, and directly to
      the contents of the cranial cavity (brain and cerebrospinal fluid) through a
      craniotomy. ABR wave I in response to BC stimuli delivered to skull bone was
      significantly longer in latency than that to BC delivered on the brain, while
      there was no latency difference between AC stimuli and BC to the brain.
      Furthermore, the vibration (measured with an accelerometer) recorded on the brain
      during BC stimulation of skull bone was always delayed compared to that measured
      on the skull. Thus there is a delay in the transfer of vibratory energy from the
      skull bone to the underlying contents of the cranial cavity. From there, the
      delayed vibrations of the contents of the cranial cavity are transmitted to the
      inner ear. This is probably the mechanism of the longer latency BC response
      compared to the AC response.

PMID- 11591497
TI  - Efficient synthesis of lactosaminylated core-2 O-glycans.
AB  - A series of lactosaminylated oligosaccharides found in mucin type O-glycans was
      synthesized using a generalized block strategy. The synthesis involved the
      addition of a protected lactosamine donor to a partially protected T-disaccharide
      derivative. The nonreducing galactose residues of the deblocked oligosaccharide
      products could be removed by beta-galactosidase from jack bean to produce the
      corresponding GlcNAc terminated compounds. A series of tri- to hexasaccharides
      was thus efficiently produced.

PMID- 11591498
TI  - Microwave assisted synthesis of N-arylphthalamic acids with hyperlipidemic
      activity.
AB  - A series of substituted N-arylphthalamic acids 3a-i has been synthesized by the
      reaction of phthalic anhydride 1 and aryl- or heterocyclic amines 2a-i, in the
      absence of solvents, in a domestic microwave oven. The formation of nine N
      arylphthalamic acids was accomplished in 1-3 min giving excellent yields for
      compounds 3a-g, but moderate yield of compounds 3h and 3i, respectively.
      Compounds 3h and 3i are new. Interestingly, N-arylphthalamic acids 3a-i induced
      hyperlipidemia in Swiss white mice and also increased animals' body weight.

PMID- 11591499
TI  - Synthesis, characterisation and antiamoebic activity of new thiophene-2
      carboxaldehyde thiosemicarbazone derivatives and their cyclooctadiene Ru(II)
      complexes.
AB  - Reaction of new thiosemicarbazones (1-4) derived from thiophene-2-carboxaldehyde
      and cycloalkylaminothiocarbonylhydrazine with [Ru(eta(4)-C8H12)(CH3CN)2Cl2] leads
      to form complexes (1a-4a) of the type [Ru(eta(4)-C8H12)(TSC)Cl2] (where
      TSC=thiosemicarbazone). All the compounds have been characterised by elemental
      analysis, IR, 1H NMR, electronic spectra and thermogravimetric analysis. It is
      concluded that the thionic sulphur and the azomethine nitrogen atom of the
      ligands are bonded to the metal ion. In vitro antiamoebic screening against (HK
      9) strain of Entamoeba histolytica indicated that the Ru(II) complexes of
      thiophene-2-carboxaldehyde thiosemicarbazones were found more active than the
      thiosemicarbazones.

PMID- 11591500
TI  - N,N'-bis[4-(N-alkylamidino)phenyl]homopiperazines as anti-Pneumocystis carinii
      agents.
AB  - The synthesis, anti-Pneumocystis carinii activity and DNA binding properties of
      eight new N,N'-bis[4-(N-alkylamidino)phenyl]homopiperazines are reported.
      Compounds 2 and 8 were the most potent and caused about 70% inhibition of
      Pneumocystis carinii growth in a cell culture model at 1 microM concentrations.

PMID- 11591501
TI  - Design and synthesis of irreversible depsipeptidyl human rhinovirus 3C protease
      inhibitors.
AB  - Novel tripeptidyl C-terminal Michael acceptors with an ester replacement of the
      P(2)-P(3) amide bond were investigated as irreversible inhibitors of the human
      rhinovirus (HRV) 3C protease (3CP). When screened against HRV serotype-14 the
      best compound was shown to have very good 3CP inhibition (k(obs)/[I]=270,000M(
      1)s(-1)) and potent in vitro antiviral activity (EC(50)=7.0nM).

PMID- 11591502
TI  - Naphthalene derivatives: A new series of selective cyclooxygenase-2 inhibitors.
AB  - A new series of potent and selective cyclooxygenase-2 inhibitors have been
      prepared. Some of these compounds show good oral anti-inflammatory activity in
      rats.

PMID- 11591503
TI  - Discovery and initial structure-activity relationships of trisubstituted ureas as
      thrombin receptor (PAR-1) antagonists.
AB  - Thrombin is the most potent agonist of platelet activation, and its effects are
      predominantly mediated by platelet thrombin receptors. Therefore, antagonists of
      the thrombin receptor have potential utility for the treatment of thrombotic
      disorders. Screening of combinatorial libraries revealed 2 to be a potent
      antagonist of the thrombin receptor. Modifications of this structure produced
      11k, which inhibits thrombin receptor stimulated secretion and aggregation of
      platelets.

PMID- 11591504
TI  - The synthesis and properties of new 2-pyrrolylthiones as chelating agents for
      transition metals and technetium.
AB  - A series of new 2-pyrrolylthiones was synthesized and found to be good chelating
      agents for transition metals and technetium.

PMID- 11591506
TI  - Regiospecific phosphohydrolases from Dictyostelium as tools for the
      chemoenzymatic synthesis of the enantiomers D-myo-inositol 1,2,4-trisphosphate
      and D-myo-inositol 2,3,6-trisphosphate: non-physiological, potential analogues of
      biologically active D-myo-inositol 1,3,4-trisphosphate.
AB  - A new de novo synthesis of the enantiomeric pair D-myo-inositol 1,2,4
      trisphosphate and D-myo-inositol 2,3,6-trisphosphate is described. Starting from
      enantiopure dibromocyclohexenediol, several C2 symmetrical building blocks were
      synthesized which gave access to D-myo-inositol 1,2,4,5-tetrakisphosphate and D
      myo-inositol 1,2,3,6-tetrakisphosphate. Exploiting the high regiospecificity of
      two partially purified phosphohydrolases from Dictyostelium, a 5-phosphatase and
      a phytase, the inositol tetrakisphosphates were converted enzymatically to the
      target compounds. Their potential to modulate the activity of Ins3,4,5,6P4 1
      kinase was investigated and compared with the effects of D-myo-inositol 1,3,4
      trisphosphate.

PMID- 11591505
TI  - Synthesis and biological evaluation of novel bisindolylmaleimides that inhibit
      vascular endothelial cell proliferation.
AB  - A novel class of bisindolylmaleimides were synthesized and antiproliferative
      activities (HUVECs and three tumor cell lines) of these compounds were
      investigated. Two water-soluble derivatives, 10 and 12, possessing a
      dimethylaminoalkoxy side chain in their structure, showed interesting activity
      and selectivity on HUVECs proliferation.

PMID- 11591507
TI  - The discovery of sulfonylated dipeptides as potent VLA-4 antagonists.
AB  - Directed screening of a carboxylic acid-containing combinatorial library led to
      the discovery of potent inhibitors of the integrin VLA-4. Subsequent optimization
      by solid-phase synthesis afforded a series of sulfonylated dipeptide inhibitors
      with structural components that when combined in a single hybrid molecule gave a
      sub-nanomolar inhibitor as a lead for medicinal chemistry. Preliminary metabolic
      studies led to the discovery of substituted biphenyl derivatives with low
      picomolar activities. SAR and pharmacokinetic characterization of this series are
      presented.

PMID- 11591508
TI  - Synthesis of N-propargylphenelzine and analogues as neuroprotective agents.
AB  - A series of N(1)- and N(2)-propargylphenelzine derivatives and analogues (1-7)
      was synthesized. In addition to their activity as monoamine oxidase inhibitors,
      two of the compounds, N(1)- and N(2)-propargylphenelzines (3 and 6), were found
      to be potent at preventing DSP-4-induced noradrenaline (NA) depletion in mouse
      hippocampus, suggesting that they have neuroprotective properties.

PMID- 11591509
TI  - alpha-Amino-beta-sulphone hydroxamates as potent MMP-13 inhibitors that spare MMP
      1.
AB  - A series of alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for
      potency versus MMP-13 and selectivity versus MMP-1. Various substituents were
      employed on the alpha-amino group (P(1) position), as well as different groups
      attached to the sulphone group extending into P(1)'. Low nanomolar potency was
      obtained for MMP-13 with selectivity versus MMP-1 of >1000x for a number of
      analogues.

PMID- 11591510
TI  - alpha-Alkyl-alpha-amino-beta-sulphone hydroxamates as potent MMP inhibitors that
      spare MMP-1.
AB  - A series of alpha-alkyl-alpha-amino-beta-sulphone hydroxamates was prepared and
      evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1.
      Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10
      to >1000. Selected compounds were orally bioavailable.

PMID- 11591511
TI  - Small molecule/nucleic acid affinity chromatography: application for the
      identification of telomerase inhibitors which target its key RNA/DNA
      heteroduplex.
AB  - The purpose of this work is to develop methods for identifying high-affinity
      nucleic acid binding species from soluble mixtures of compounds. We have
      developed and applied an affinity chromatography method for identifying small
      molecules with high affinity for the telomerase RNA/DNA duplex. An affinity resin
      was derivatized with an RNA/DNA duplex which represents the key structure that
      forms during telomerase's catalytic cycle. A soluble mixture of compounds was
      applied to this resin and the compounds which bound to the highest extent were
      also confirmed to be the best inhibitors of the enzyme. This correlation of
      affinity for the RNA/DNA duplex with telomerase inhibition both supports the
      duplex as the target of these compounds, and suggests that the affinity method
      may be applied for the identification of higher affinity inhibitors from soluble
      mixtures of compounds.

PMID- 11591512
TI  - Small molecule somatostatin receptor subtype-2 antagonists.
AB  - The first potent small molecule sst2 antagonists are reported. Altering known
      sst2 agonist molecules yielded compounds with high sst2 binding affinity and full
      antagonist activity. Compound 7a, for example, displaced somatostatin binding to
      the sst2 receptor with an IC(50)=2.9 nM and antagonized somatostatin action with
      an IC(50)=29nM.

PMID- 11591513
TI  - Mixed kappa agonists and mu agonists/antagonists as potential
      pharmacotherapeutics for cocaine abuse: synthesis and opioid receptor binding
      affinity of N-substituted derivatives of morphinan.
AB  - A series of new N-substituted derivatives of morphinan was synthesized and their
      binding affinity for the three opioid receptors (mu, delta, and kappa) was
      determined. A paradoxical effect of N-propargyl (MCL-117) and N-(3-iodoprop-(2E)
      enyl) (MCL-118) substituents on the binding affinities for the mu and kappa
      opioid receptors was observed. All of these novel derivatives showed a preference
      for the mu and kappa versus delta binding.

PMID- 11591515
TI  - Synthesis and progesterone receptor antagonist activities of 6-aryl
      benzimidazolones and benzothiazolones.
AB  - Novel 6-aryl benzimidazolones and benzothiazolones were prepared and examined as
      bioisosteres of the recently reported 6-aryl dihydroquinolines (1) for
      progesterone receptor (PR) antagonist activities. PR antagonist activities
      increased when compounds 9c-f possessed a more lipophilic group at position-1 and
      pendent aryl moiety para to NH moiety. Furthermore, conversion of carbonyl moiety
      of 9e,f to the thio-carbonyl led to benzoimidazolethiones 15a,b with
      significantly improved potency and binding affinity.

PMID- 11591514
TI  - 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 2: lead
      optimization affording selective, orally bioavailable compounds with potent anti
      HIV activity.
AB  - Investigations of the structure-activity relationships of 1,3,4-trisubstituted
      pyrrolidine human CCR5 receptor antagonists afforded orally bioavailable
      compounds with the ability to inhibit HIV replication in vitro.

PMID- 11591516
TI  - Synthesis and structure-activity relationships of thiotetronic acid analogues of
      thiolactomycin.
AB  - 3-Acetyl analogues of thiolactomycin, a thiotetronic acid natural product, were
      synthesized and profiled against livestock pathogens. Some analogues showed
      improved activity over thiolactomycin against Staphylococcus aureus and
      comparable activity against Pasteurella multocida. Several semisynthetically
      modified analogues of thiolactomycin showed no improvement in activity over
      thiolactomycin.

PMID- 11591517
TI  - Anti-Trypanosoma activity of some natural stilbenoids and synthetic related
      heterocyclic compounds.
AB  - We report the anti-Chagasic activity of the natural dihydrostilbenoid
      isonotholaenic acid and several simple derivatives, as well as that of some
      representative compounds of related synthetic series, with basic structures of
      benzalphthalides, dihydrostilbamides, isoindoles, phthalazin-1-ones, imidazo[2,1
      a]isoindoles and pyrimido[2,1-a]isoindoles. The evaluation was performed in vitro
      on cultures of epimastigote and trypomastigote forms of Trypanosoma cruzi. Some
      of the tested compounds resulted to be as potent as benznidazole (epimastigotes),
      and others were shown to be more active than gentian violet (trypomastigotes),
      used as reference drugs.

PMID- 11591519
TI  - Simplified catechin-gallate inhibitors of HIV-1 reverse transcriptase.
AB  - Systematic simplification of the molecular structures of epicatechin gallate and
      epigallocatechin gallate to determine the minimum structural characteristics
      necessary for HIV-1 reverse transcriptase inhibition in vitro resulted in several
      compounds that strongly inhibited the native as well as the A17 double mutant
      (K103N Y181C) enzyme, which is normally insensitive to most known nonnucleoside
      inhibitors.

PMID- 11591518
TI  - Potent second generation vinyl sulfonamide inhibitors of the trypanosomal
      cysteine protease cruzain.
AB  - A new family of potent N-alkoxyvinylsulfonamide inhibitors of cruzain have been
      developed. Inhibitor 13 has a second order inactivation rate constant of
      6,480,000s(-1)M(-1) versus cruzain, and is also highly effective against
      Trypanosoma cruzi trypomastigotes in a tissue culture assay.

PMID- 11591520
TI  - Discovery of novel, orally active dual NK1/NK2 antagonists.
AB  - Exploration of the SAR around selective NK2 antagonists, SR48968 and ZD7944, led
      to the discovery that naphth-1-amide analogues provide potent dual NK1 and NK2
      antagonists. ZD6021 inhibited binding of [3H]-NKA or [3H]-SP to human NK1 and NK2
      receptors, with high-affinity (K(i)=0.12 and 0.62nM, respectively). In functional
      assays ZD6021 had, at 10(-7)M, in human pulmonary artery pK(B)=8.9 and in human
      bronchus pK(B)=7.3, for NK1 and NK2, respectively. Oral administration of ZD6021
      to guinea pigs dose-dependently attenuated ASMSP induced extravasation of plasma
      proteins, ED(50)=0.5mg/kg, and NK2 mediated bronchoconstriction, ED(50)=13mg/kg.

PMID- 11591521
TI  - Discovery of heterocyclic ureas as a new class of raf kinase inhibitors:
      identification of a second generation lead by a combinatorial chemistry approach.
AB  - Heterocyclic ureas, such as N-3-thienyl N'-aryl ureas, have been identified as
      novel inhibitors of raf kinase, a key mediator in the ras signal transduction
      pathway. Structure-activity relationships were established, and the potency of
      the screening hit was improved 10-fold to IC(50)=1.7 microM. A combinatorial
      synthesis approach enabled the identification of a breakthrough lead (IC(50)=0.54
      microM) for a second generation series of heterocyclic urea raf kinase
      inhibitors.

PMID- 11591522
TI  - Structure-based design of caspase-1 inhibitor containing a diphenyl ether
      sulfonamide.
AB  - A series of compounds was designed and prepared as inhibitors of interleukin
      1beta converting enzyme (ICE), also known as caspase-1. These inhibitors, which
      employ a diphenyl ether sulfonamide, were designed to improve potency by forming
      favorable interactions between the diphenyl ether rings and the prime side
      hydrophobic region. An X-ray crystal structure of a representative member of the
      diphenyl ether sulfonamide series bound to the active site of caspase-1 was
      obtained.

PMID- 11591523
TI  - Total synthesis and antifungal activity of 9-methoxystrobilurin L as the
      originally proposed 1,4-benzodioxan structure.
AB  - Total synthesis of both enantiomers of 9-methoxystrobilurin L as the originally
      proposed 1,4-benzodioxan structure was successfully achieved. The 1H and 13C NMR
      spectra of synthesized 9-methoxystrobilurin L were compared with those of a
      naturally-occurring sample. It was strongly indicated that naturally-occurring 9
      methoxystrobilurin L has not the originally reported 1,4-benzodioxan structure
      but a 1,5-benzodioxepin structure, the same as previously reported 9
      methoxystrobilurin K. Antifungal activities of the synthesized compounds toward
      several typical fungi were also examined, and they were less active than 9
      methoxystrobilurin K.

PMID- 11591524
TI  - NaBH4 in N-methylpyrrolidone: a safe alternative for hydride displacement
      reaction.
AB  - Enhanced reactivity of NaBH4 was observed as a solution in N-methylpyrrolidone
      (NMP). Thus, a simple protocol for debromination of alkyl bromide and sulfonate
      is devised with NMP as a key solvent. Also described is a new mixed borohydride
      system, NaBH4-LiOTf-NMP, which works as an alternative to NaBH3CN for the SN2
      type displacement. No reports have ever revealed usefulness of NMP in borohydride
      reduction.

PMID- 11591527
TI  - The fibrinolytic system in chronic renal failure.
AB  - BACKGROUND: Patients with chronic renal failure (CRF) face a high risk of
      cardiovascular morbidity and mortality. Impaired fibrinolysis has recently been
      acknowledged to function as a risk factor for cardiovascular ischemic
      complications. Whether changes in fibrinolytic function contribute to the
      increased cardiovascular risk in CRF, however, remains unclear. METHODS: In the
      present study, tissue-plasminogen activator (t-PA) and its main antagonist
      plasminogen activator inhibitor-1 (PAI- 1) were determined in 12 subjects with
      normal renal function (group A) [serum creatinine (Cr) <1.3 mg/dl], 24 patients
      with impaired renal function (Cr 1.3-6.5 mg/dl) (group B) and 22 patients with
      endstage renal disease (ESRD) on hemodialysis (Cr>6.5 mg/dl) (group C). RESULTS:
      Plasma concentrations of PAI-1 and t-PA antigen as well as the PAI-1:t-PA molar
      ratio were unchanged in group B as compared to group A. However, in ESRD patients
      (group C), t-PA concentrations markedly decreased [13.7 +/- 2.9 ng/ml vs. 32.8 +/
      4.7 ng/ml (group B, p <0.01) and 35.4 +/- 8.4 ng/ml (group A, p <0.01)] while
      PAI-1 antigen concentrations remained in the control range. Thus, the PAI-1:t-PA
      molar ratio significantly increased in group C patients [12.4 +/- 4. 0 vs. 6.0 +/
      2.5 (group B; p<0.01) and 4.5 +/- 1.7 (group A; p<0.01]. CONCLUSIONS: From our
      data it may be suggested that fibrinolysis is markedly disturbed in ESRD due to a
      decreased availability of t-PA. Thus, it may be speculated that the development
      of atherothrombotic events in hemodialysis patients is, at least in part, due to
      an impaired fibrinolysis.

PMID- 11591528
TI  - Analysis of 1202 orthopantograms to evaluate the potential of forensic age
      determination based on third molar developmental stages.
AB  - A total of 1202 orthopantograms of young dental patients were analyzed to assess
      the correlation of third molar root development with chronological age. The
      investigated patients were treated at a university dental clinic on an outpatient
      basis, included a variety of demographic characteristics (600 males and 602
      females, 28% of other than central European background), and were 15-24 years old
      when the radiographs were obtained. Radiographs in which more than one third
      molar were either missing due to agenesia or extraction, or not evaluable because
      of deep destruction or marked tilting, were not included in the analysis. Our
      findings show that the growth patterns of third molars, based on seven defined
      stages of root development, did correlate with chronological age; age estimation
      when applied to a specific individual would involve a margin of error of +/- 2-4
      years. There were no significant differences between the left and right jaw
      segments, but the stage of root development was generally more advanced in the
      upper than in the lower third molars. Root development was also more advanced
      among boys than among girls of the same age. There were no apparent differences
      in growth patterns based on national/ethnic background. While only 2.5% of 18
      year-olds revealed fully developed third molars in all four quadrants, this
      percentage leaped to 38.4% among the 21-year-olds. To summarize, while the
      developmental stage of third molars is not per se a highly useful indicator of
      chronological age in juveniles and young adults, it is nevertheless a valuable
      supplementary parameter given the scarcity of other available age indicators.

PMID- 11591529
TI  - Endosonography of insulin-secreting and clinically non-functioning neuroendocrine
      tumors of the pancreas: criteria for benignancy and malignancy.
AB  - OBJECTIVE: Endosonography is a powerful tool in the diagnosis of
      gastroenteropancreatic neuroendocrine tumors. This study was performed in order
      to characterize endosonographic criteria of malignant and benign neuroendocrine
      pancreatic tumors focussing on those typically presented to endocrinologists,
      i.e. insulin-secreting tumors and clinically non-functioning tumors in MEN-1.
      DESIGN: We studied six benign insulinomas, four hormone inactive benign
      neuroendocrine adenomas in MEN-1, and three non-metastatic neuroendocrine
      carcinomas with clinically symptomatic insulin secretion. METHODS: Endosonography
      was performed using Pentax FG 32 UA endosonoscope with a longitudinal 7.5 MHz
      sector array. RESULTS: Tumor diameter was larger in malignant tumors (19 - 70 /
      47.0 +/- 25.9 mm) than in benign lesions (2.3 - 19 / 9.7 +/- 5.8 mm). Hypoechoic
      echogeneity was more or less present in benign and in malignant tumors and could
      not be used as a criteria for differential diagnosis. Heterogeneous or
      multinodular structure on endosonographic imaging however, was an exclusive
      feature of malignant tumors. Echo-free areas representing cystic transformation
      or necrosis and vascular invasion were additional signs of malignancy.
      CONCLUSIONS: Molecular genetic diagnosis of MEN-1 and new therapeutic
      developments such as endoscopic surgery make sufficient imaging procedures in the
      management of neuroendocrine pancreatic tumors mandatory. Besides valid detection
      and exact localization, endosonography provides criteria for benign and malignant
      tumors and thus may be helpful in planning therapeutic strategies.

PMID- 11591530
TI  - Topical application of vitamin A reverses metaplasia of rat vaginal epithelium: a
      rapid and efficient approach to improve mucosal barrier function.
AB  - Retinyl palmitate and its metabolites retinol and retinoic acid control growth
      and epithelial differentiation. Systemic or local vitamin A deficiency induced by
      malnutrition, continuous chemical irritation or locally induced by inflammation
      causes squamous metaplastic changes in the epithelium of mucous membranes. We
      demonstrate that in an animal model topically applied retinyl palmitate can be
      taken up by the mucosal cells independently from the systemic supply. Under in
      vivo conditions metabolic changes in vaginal epithelium of rats were shown to be
      reversed by treatment with topical retinyl palmitate. - After only two days
      treatment squamous metaplastic vaginal epithelium in rats shows a reversal of the
      epithelium into a normal phenotype which continues after cessation of the
      treatment for 7 to 11 days. Higher concentrations and longer retention times lead
      to a statistically significant (p = 0.025) increase in the protection time. These
      data demonstrate that squamous changes induced by vitamin A deficiency can be
      totally reversed with topically applied retinyl palmitate.

PMID- 11591531
TI  - Cigarette smoking among Iranian medical students, resident physicians and
      attending physicians.
AB  - OBJECTIVE: This research assessed the prevalence of cigarette smoking among
      Iranian medical students, resident physicians and attending physicians. METHODS:
      Subjects (532 males and females) were selected randomly from Shiraz university of
      medical sciences and were administered by a questionnaire. FINDINGS: Of the
      participants 16.79% of males and 0.69% of females were smokers. Of the medical
      students, 18.48% of students, 12.5% of pre-externship students, 7.19% of
      externship students and 16.95% of internship students were smokers. Of resident
      physicians 11.11% were smokers. Among attending physicians 7.57% were smokers.
      The most common causes of current cigarette smoking were need (avoid withdrawal
      symptoms), pleasurable purposes and release of tension, respectively. Foreign
      filter tipped cigarette was the most common type of cigarette used. The mean of
      cigarette per day was 6.29 cigarettes and the mean age of starting cigarette was
      19.71 years.

PMID- 11591532
TI  - Lack of association between burning mouth syndrome and hematinic deficiencies.
AB  - The aim of our investigation was to evaluate possible connection between burning
      mouth syndrome and hematinic deficiencies, a hypothesis previously reported in
      the literature with contradictory results. Serum levels of iron, vitamin B12,
      folic acid, calcium and magnesium were determined in 41 (aged 31-87 years, mean
      68,7 yrs) patients with burning mouth syndrome and 35 matched controls (35-83,
      mean 63 yrs). Serum iron levels were determined according to Fairbanks and Klee.
      Levels of vitamin B12 and folic acid were determined on commercially available
      kits (Imx12 and Imx folate assay, Abbot Park lab, IL, USA) on Imx analyser.
      Calcium and magnesium levels were determined using atomic absorption
      spectrophotometry. No statistically significant differences in serum levels of
      iron, folic acid, calcium and magnesium were found between patients with burning
      mouth syndrome and controls. Statistically significant lowered vitamin B12 levels
      were found in patients with burning mouth syndrome. Our results suggest that
      serum deficiencies of iron, folic acid, calcium and magnesium are not etiological
      factor in patients with burning mouth syndrome.

PMID- 11591533
TI  - The "economy class syndrome": problems with the assessment of risk factors for
      venous thromboembolism.

PMID- 11591534
TI  - Can Legionnaires disease be diagnosed by clinical criteria? A critical review.

PMID- 11591535
TI  - Severe community-acquired pneumonia: the need to customize empiric therapy.

PMID- 11591536
TI  - Hypersensitivity pneumonitis: just think of it!

PMID- 11591537
TI  - A simple method to assess postoperative risk.

PMID- 11591538
TI  - Emergency department visits in asthma: should all be prevented?

PMID- 11591539
TI  - Predicting extubation failure: is it in (on) the cards?

PMID- 11591540
TI  - Evaluation of the Winthrop-University Hospital criteria to identify Legionella
      pneumonia.
AB  - STUDY OBJECTIVE: To measure the ability of a set of clinical parameters, the
      Winthrop-University Hospital (WUH) criteria, to identify Legionella pneumonia
      while discriminating against bacteremic pneumococcal pneumonia at the time of
      hospitalization for community-acquired pneumonia (CAP). DESIGN: Retrospective
      case-control study. SETTING: An urban county hospital and a tertiary-care
      Veterans Affairs hospital. PATIENTS: Thirty-seven patients with Legionella
      pneumonia (diagnosed by a positive result of a urinary Legionella antigen test)
      and 31 patients with bacteremic pneumococcal pneumonia. A subgroup of patients
      with all required laboratory criteria were studied further. RESULTS: The WUH
      criteria correctly identified 29 of 37 patients with Legionella pneumonia
      (sensitivity, 78%; 95% confidence interval [CI], 61 to 90%), while successfully
      excluding legionellosis in 20 of 31 patients with bacteremic pneumococcal
      pneumonia (specificity, 65%; 95% CI, 45 to 80%). The positive and negative
      predictive values, adjusted for a relative prevalence of 1:3 between Legionella
      and Streptococcus pneumoniae bacteremia, were 42% (95% CI, 25 to 61%) and 90%
      (95% CI, 74 to 97%), respectively. In the subgroup analysis, the WUH criteria
      were successful in identifying 20 of 23 patients with Legionella pneumonia
      (sensitivity, 87%; 95% CI, 65 to 97%), while excluding legionellosis in 9 of 18
      patients with bacteremic pneumococcal pneumonia (specificity, 50%; 95% CI, 27 to
      73%). The adjusted positive and negative predictive values for a 1:3 relative
      prevalence were 37% (95% CI, 20 to 59%) and 92% (95% CI, 62 to 98%),
      respectively. The predictive values were changed in the directions expected for
      an increased relative prevalence of 1:1. The areas under the receiver operating
      characteristic curves were 0.72 +/- 0.06 for the entire study group and 0.68 +/-
      0.09 for the subgroup. CONCLUSIONS: Although the WUH criteria discriminated
      fairly well between cases (mean +/- SE) and control subjects, the sensitivity is
      not high enough to exclude legionellosis confidently. These results suggest that
      empiric therapy for Legionella pneumonia should be included in the initial
      antibiotic regimen for hospitalized patients with CAP.

PMID- 11591541
TI  - Severe community-acquired pneumonia due to Acinetobacter baumannii.
AB  - STUDY OBJECTIVES: To investigate the clinical, epidemiologic, and microbiological
      characteristics of community-acquired pneumonia (CAP) due to Acinetobacter
      baumannii. METHODS: Retrospective chart and radiographic reviews of all patients
      who were admitted to National Taiwan University Hospital from January 1993 to
      August 1999, fulfilled the criteria for CAP, and had an isolate of A. baumannii
      from blood or pleural fluid at hospital admission. RESULTS: Thirteen patients (9
      men and 4 women; age range, 37 to 85 years) met the criteria. Conditions
      associated with the infection included male gender, old age, alcoholism,
      malignancy, cerebrovascular disease, diabetes mellitus, renal disease, and liver
      cirrhosis. Eleven patients (85%) acquired the infection during the warmer months
      of April to October. Twelve patients (92%) had a fulminant course presenting with
      septic shock and respiratory failure, and 11 patients (85%) needed ventilator
      support and were treated in an ICU. Six patients (46%) had leukopenia. Lobar
      consolidations were found in 12 patients (92%), and pleural effusions were
      present in 4 patients (31%). All patients had positive blood culture results, two
      patients (15%) had positive pleural effusion culture findings, and nine patients
      (69%) positive sputum culture results. All the isolates were susceptible to
      imipenem, and most were susceptible to aminoglycosides, ceftazidime,
      ciprofloxacin, and extended-spectrum penicillins. Eight patients (62%) died. Four
      of the five survivors were initially treated with combination of a third
      generation cephalosporin and an aminoglycoside. CONCLUSION: A. baumannii should
      be considered as a possible etiologic agent in community-acquired lobar pneumonia
      when (1) patients with a fulminant course present during the warmer and more
      humid months of the year, and (2) patients are younger alcoholics. A good sputum
      smear, defined as a Gram stain smear of an adequate sputum specimen that comes
      from the lower respiratory tract and contains > 25 leukocytes per high-power
      (100x) field on microscopic examination, can help early diagnosis and treatment.
      A combination of a third-generation cephalosporin and an aminoglycoside may be
      appropriate empirical therapy.

PMID- 11591542
TI  - AIDS-related alveolar hemorrhage: a prospective study of 273 BAL procedures.
AB  - STUDY OBJECTIVES: To evaluate the frequency and diagnostic significance of
      alveolar hemorrhage (AH) in HIV-infected patients. DESIGN: A 3-year prospective
      cohort study. SETTING: A university hospital in Paris, France. PATIENTS: Two
      hundred forty-three HIV-infected patients undergoing 273 BAL procedures during
      the study period. METHODS: AH was assessed by using the Golde score. Data on the
      patients treated and observed in our institution were collected, as well as on
      their survival rate 12 months after undergoing BAL. Risk factors for AH were
      sought by comparing patients with AH (cases) and those without AH (control
      subjects). RESULTS: AH frequently occurred but usually was subclinical and
      cytologically mild. AH did not alter the 12-month survival rate. AH always was
      associated with at least one specific AIDS-related pulmonary disorder, and the
      following four independent risk factors were identified in a stepwise forward
      logistic regression model: pulmonary Kaposi's sarcoma (KS; odds ratio [OR], 5.3;
      95% confidence interval [CI], 1.8 to 16.7; p = 0.003), cytomegalovirus (CMV)
      pneumonia (OR, 9.8; 95% CI, 1 to 100; p = 0.05), hydrostatic pulmonary edema (OR,
      16.4; 95% CI, 1.8 to 142; p = 0.01), and platelet count < 60,000 cells/microL
      (OR, 5.6; 95% CI, 1.5 to 20; p = 0.009). CONCLUSIONS: AH is frequently diagnosed
      during BAL in HIV-infected patients. Its presence may point to an underlying
      cause, such as pulmonary KS, CMV pneumonia, or hydrostatic pulmonary edema, or to
      triggering factors such as thrombocytopenia.

PMID- 11591543
TI  - Hypersensitivity pneumonitis induced by spores of Lyophyllum aggregatum.
AB  - OBJECTIVES: Lyophyllum aggregatum (LA) is called Shimeji in Japanese and is eaten
      commonly as a mushroom. Shimeji mushrooms are cultivated in an indoor environment
      all year round. This study aimed to clarify the clinical features of
      hypersensitivity pneumonitis (HP) induced by LA. PATIENTS AND SETTING: Ten
      patients showed mild respiratory symptoms including dry cough, sputum, and low
      grade fever. We tried to characterize the clinical features and the findings
      using chest high-resolution CT (HRCT), pulmonary function tests (PFTs), and BAL
      fluid (BALF) tests in patients with HP induced by LA. HP was diagnosed from
      clinical features, HRCT findings, BALF findings, lung histology, and lymphocyte
      stimulation tests (LSTs) for LA. RESULTS: Laboratory findings showed mean (+/-
      SD) elevated levels of C-reactive protein (0.78 +/- 1.3 mg/dL), erythrocyte
      sedimentation rate (48 +/- 23 mm/h), and gamma-globulin (26.9 +/- 7.6%). PFTs
      revealed a slight decrease in the percentage diffusing capacity of the lung for
      carbon monoxide, possibly due to the presence of epithelial granulomas in the
      alveoli. Although 4 of 10 patients showed normal findings on the chest radiograph
      (CXR), chest HRCT findings of all patients showed centrilobular small nodules and
      diffuse ground-glass opacities. The BALF testing revealed an increase in total
      cell counts, showing predominantly activated T lymphocytes. The CD4/CD8 cell
      ratio was significantly decreased (0.5 +/- 0.3). The results of the LSTs were
      positive in seven of seven cases. CONCLUSIONS: Since patients with HP induced by
      LA typically have mild respiratory symptoms and sometimes normal CXR findings,
      their conditions might remain undiagnosed. However, the chest HRCT images showed
      the typical subacute phase of HP.

PMID- 11591544
TI  - Fiberoptic bronchoscopy in allogeneic bone marrow transplantation: findings in
      the era of serum cytomegalovirus antigen surveillance.
AB  - STUDY OBJECTIVES: Pulmonary complications occur in half of allogeneic bone marrow
      transplantation (BMT) patients. The incidence of these complications has been
      reduced by prophylaxis against Pneumocystis carinii pneumonia, preemptive therapy
      in patients at high risk for cytomegalovirus (CMV) reactivation, and, more
      recently, screening for serum CMV antigen. Since fiberoptic bronchoscopy (FOB)
      has historically been the primary diagnostic test to evaluate BMT patients with
      pulmonary disease, a review was performed to determine the impact, if any, that
      current prophylaxis and screening policies may have had on FOB utility. DESIGN:
      The records of 174 adult patients undergoing BMT between January 1997 and
      December 1999 were reviewed to determine the diagnostic yield of FOB and the
      frequency by which FOB altered management. RESULTS: Sixty-one patients underwent
      76 bronchoscopies. FOB was diagnostic in 32 patients (42.1% of cases) and
      directly changed management in 24 patients (31.6% of cases). Half of these
      changes included the withdrawal of an antimicrobial agent. The most common
      findings were infection (32 cases) and diffuse alveolar hemorrhage (6 cases). CMV
      was the most prevalent infection identified, but FOB resulted in the addition of
      antiviral therapy to only two patients. P carinii pneumonia was not diagnosed in
      any patient studied. CONCLUSIONS: These data suggest a changing spectrum of
      pulmonary disease in BMT patients. FOB has limited impact on the diagnoses of CMV
      disease or P carinii pneumonia with current prophylaxis and screening strategies.
      It may be useful in identifying other infectious etiologies and in eliminating
      unnecessary antimicrobials.

PMID- 11591545
TI  - Bronchiolitis obliterans in the 1990s in Korea and the United States.
AB  - STUDY OBJECTIVES: Our current knowledge of pediatric bronchiolitis obliterans
      (BO) is based largely on a few small series of patients that were reported in the
      older literature. In these older cases, the mortality rate was high. This study
      was conducted to investigate the characteristics of pediatric BO cases in two
      different countries. DESIGN: We extracted specific information regarding
      predisposing factors, symptoms and signs, diagnostic studies, treatment, and
      outcome from the medical records of 31 children who received diagnoses of BO at
      four university medical centers in Korea and the United States in the 1990s.
      RESULTS: The large number of Asian children reflects a clustering of cases in
      Korea due to adenovirus and Mycoplasma pneumoniae epidemics. The characteristic
      diagnostic features of BO were present in 29 of 30 high-resolution CT (HRCT)
      studies. Seven of nine children who underwent biopsies had histologic
      confirmations of BO. In two patients whose biopsy results were nondiagnostic, the
      diagnosis was established by HRCT together with pulmonary function testing
      results that were consistent with nonreversible small airways obstruction.
      Fifteen children (48.4%) had evidence of hypoxemia. At present, all but one are
      alive. Patients with elevated severity-of-illness scores were observed to have
      increased likelihoods of lung transplantation or death. CONCLUSIONS: We conclude
      that BO has a good overall prognosis and that the mortality rate has declined
      over the past decade. This could be related primarily to the use of HRCT for
      accurate diagnosis and the availability of pediatric lung transplantation. BO
      cases in Korea were associated with infectious epidemics, whereas those in United
      States had variable predisposing factors.

PMID- 11591546
TI  - Differential cell counts in sputum in respiratory epidemiology: a pilot study.
AB  - BACKGROUND: The aim of this pilot study was to determine whether measuring sputum
      differential cell counts, particularly eosinophils, could be a useful method of
      validating self-reported symptoms suggesting asthma in epidemiologic studies.
      MATERIALS AND METHODS: In this cross-sectional study, we selected four groups of
      adult subjects by reported symptoms and diagnoses from among those previously
      randomly identified in a population study. Subjects were selected with no
      respiratory symptoms ever (normal group), or reporting a diagnosis of asthma
      (asthma group), or reporting recurrent wheezing not diagnosed as asthma (wheeze
      group), or reporting exposure to industrial irritants, but not asthma or wheezing
      (exposed group). Current respiratory symptoms, airway responsiveness to
      methacholine challenge, and sputum cell counts were determined. The study was
      completed by 107 subjects aged 20 to 44 years. RESULTS: There were no significant
      differences in FEV(1) percent predicted, total cell count, and sputum eosinophil
      count among the four groups. Subjects with reported asthma had greater airway
      responsiveness as reflected in a lower bronchial reactivity (BR) index. There was
      a weak correlation between BR index and sputum eosinophils. CONCLUSION: In a
      community setting, induced sputum eosinophil cell counts in subjects reporting
      asthma or wheezing were most often within the normal range and not sufficiently
      often abnormal to be useful in validating a diagnosis of asthma in epidemiologic
      studies.

PMID- 11591547
TI  - Airway inflammation as an assessment of chronic nonproductive cough.
AB  - OBJECTIVES: The possibility that a bronchial inflammatory process could be
      involved with a chronic nonproductive cough without other potential causes such
      as postnasal drip syndrome, bronchial asthma, gastroesophageal reflux, chronic
      bronchitis, bronchiectasis, or the use of angiotensin-converting enzyme
      inhibitors has not been clearly described. We investigated the possibility that a
      chronic nonproductive cough without other potential causes is associated with
      airway inflammation, and if this is so, what the relationship might be between
      this inflammation and the possible etiology of the cough. SUBJECTS: Twenty-five
      adults with chronic nonproductive cough as an isolated symptom over a 3-week
      period, and 5 healthy control subjects were studied. MEASUREMENTS AND RESULTS:
      Clinical assessments, cough scores, methacholine challenges, allergy skin prick
      tests, and bronchoscopies for bronchial biopsies were performed. In the bronchial
      biopsies, the patients were divided into the following two subgroups: 21 patients
      who were infiltrated with eosinophils vs the healthy control group (median, 12.0
      vs. 0.0 cells/mm(2), respectively; p < 0.01); and 4 patients who were infiltrated
      with lymphocytes vs the healthy control group (median, 84.5 vs. 22.0 cells/mm(2),
      respectively; p < 0.01). With the methacholine challenge test, 5 of the 21
      eosinophil-infiltrated patients received diagnoses of cough-variant asthma, and
      the other 16 patients received diagnoses of eosinophilic bronchitis. In the
      lymphocyte-infiltrated group, all four patients received diagnoses of lymphocytic
      bronchitis. CONCLUSIONS: These results suggest that a chronic nonproductive cough
      as an isolated symptom is associated with airway inflammation due to eosinophil
      and lymphocyte infiltration. The causes of the chronic nonproductive cough were
      eosinophilic bronchitis, cough-variant asthma, and lymphocytic bronchitis.

PMID- 11591548
TI  - Application and validation of a computerized cough acquisition system for
      objective monitoring of acute cough: a meta-analysis.
AB  - STUDY OBJECTIVE: The purpose of the meta-analysis was to understand the
      antitussive effect of treatment with dextromethorphan hydrobromide, 30 mg, vs
      placebo over a 3-h treatment period in patients with cough due to uncomplicated
      upper respiratory tract infection (URTI), and to show that the computerized
      system for acquisition and analysis of cough sound was consistent and
      reproducible across the individual studies. STUDY DESIGN: The six studies used
      for the meta-analysis were randomized, double-blind, parallel-group, single-dose,
      placebo-controlled studies with a 3-h postdose cough evaluation period. SETTING:
      One study was conducted in Durban, South Africa, and five studies were conducted
      in Bombay, India. Four studies took place in clinics, and two studies were in
      home studies. PATIENTS: Seven hundred ten adult patients with cough due to
      uncomplicated URTI who were otherwise healthy and who satisfied the
      inclusion/exclusion criteria for the meta-analysis. MEASUREMENTS AND RESULTS: For
      each patient, a standard baseline was calculated pretreatment, then a 3-h
      continuous cough recording was made after treatment was initiated. Five efficacy
      variables were measured in 30-min intervals: cough bouts, cough components, cough
      effort, cough intensity, and cough latency. The meta-analysis showed consistent
      results across most of the studies for each of the efficacy variables. It
      demonstrated significantly greater overall reductions in cough bouts, cough
      components, and cough effort, and an increase in cough latency for patients
      treated with dextromethorphan hydrobromide, 30 mg, vs those treated with placebo.
      CONCLUSION: The results of a meta-analysis of the six clinical studies show that
      the antitussive effect of a single dose of dextromethorphan hydrobromide, 30 mg,
      has been established. The consistent nature of the results shows that the
      computerized cough acquisition and analysis system is a valid and reproducible
      methodology for evaluating cough associated with URTI.

PMID- 11591549
TI  - Patterns and predictors of asthma-related emergency department use in Harlem.
AB  - STUDY OBJECTIVES: To assess the roles of poor access to care, psychological risk
      factors, and asthma severity in frequent emergency department (ED) use. DESIGN: A
      cross-sectional survey. SETTING: Harlem Hospital Center ED and outpatient chest
      clinic. PARTICIPANTS: Three hundred seventy-five adult residents of Harlem, a
      predominantly African-American community in New York City. MEASUREMENTS: Asthma
      severity was assessed by self-reported symptoms using National Asthma Education
      and Prevention Program guidelines, health-care utilization, and psychometric
      scales. RESULTS: Respondents with more severe asthma were more likely to have a
      primary asthma care provider, and to have had more scheduled office visits for
      asthma in the year prior to the interview (mean number of visits for patients
      with severe asthma, 3.6 visits; moderate asthma, 2.4 visits; and mild asthma, 1.7
      visits). Despite having a regular source of care, 69% of respondents identified
      the ED as their preferred source of care; 82% visited the ED more than once in
      the year prior to interview (median, four visits). Persons with moderate or
      severe asthma were 3.8 times more likely to be frequent ED users compared to
      those with mild asthma (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.2
      to 6.6). This was the strongest predictor of frequent ED use. Other predictors of
      ED use were number of comorbid disorders (OR, 1.5; 95% CI, 1.1 to 2.1) and self
      reported global health in the year prior to the ED visit (OR, 1.8; 95% CI, 1.2 to
      2.7). Psychological characteristics were not predictive of frequent ED use when
      controlling for disease severity. CONCLUSIONS: Frequent ED users present with
      serious medical conditions. They do not substitute physician care with ED care;
      they augment it to address serious health needs.

PMID- 11591550
TI  - Elevated concentrations of exhaled hydrogen peroxide in asthmatic patients.
AB  - BACKGROUND: Airway inflammation is important in the development and progression
      of asthma. Activation of inflammatory cells induces a respiratory burst resulting
      in the production of reactive oxygen species, such as H(2)O(2). The aim of this
      study was to measure the concentration of H(2)O(2) in exhaled breath condensate
      and its correlation with airway obstruction, airway hyperresponsiveness, and
      concentration of eosinophil cationic protein (ECP) in serum in 70 steroid-naive,
      atopic patients with unstable asthma (20 men; age range, 18 to 62 years) and 17
      normal subjects (7 men; age range, 19 to 34 years). METHODS: Exhaled H(2)O(2) was
      measured using a colorimetric assay, and the concentration of ECP in serum was
      measured using radioimmunoassay. Airway hyperresponsiveness was expressed as the
      provocative concentration of inhaled histamine causing a 20% fall in FEV(1)
      (PC(20)). RESULTS: In patients with asthma, the mean H(2)O(2) concentration was
      significantly elevated compared to values in normal subjects: 0.127 +/- 0.083
      mol/L vs 0.024 +/- 0.016 mol/L (p < 0.001). There was a significant correlation
      among H(2)O(2) concentration, FEV(1), PC(20), and ECP in serum. CONCLUSION: We
      conclude that exhaled H(2)O(2) is significantly elevated in asthmatic patients.
      This is correlated with disease severity and indirect markers of airway
      inflammation. Measurement of exhaled H(2)O(2) may be useful to assess airway
      inflammation and oxidative stress in asthmatic patients.

PMID- 11591551
TI  - Effect of inhaled budesonide on bronchial hyperresponsiveness in adolescents with
      clinical remission of asthma.
AB  - STUDY OBJECTIVE: Many children with asthma go into long-term clinical remission
      at adolescence, but bronchial hyperresponsiveness (BHR) persists in some of these
      subjects. The regular use of inhaled corticosteroids improves BHR in patients
      with symptomatic asthma. The aim of this study was to determine whether BHR in
      adolescents with asthma remission could be reduced by prolonged treatment with
      inhaled corticosteroids. DESIGN: A randomized, double-blind, placebo-controlled,
      parallel study. PATIENTS: Thirty-seven adolescents with BHR and long-term
      remission of their asthma (neither symptoms nor any medication use during the
      previous 2 years). INTERVENTION: Subjects received inhaled budesonide (two 200
      microg puffs bid; budesonide group, n = 19) or identical placebo (placebo group,
      n = 18) for 9 months. A separate group of patients with symptomatic asthma
      (symptomatic group, n = 19), using the same regimen of budesonide, was also
      studied. MEASUREMENTS AND RESULTS: The provocative concentration of methacholine
      producing a 20% fall in FEV(1) (PC(20)) was measured before and every 3 months
      during treatment. There was no significant difference among the three groups for
      the baseline PC(20). In neither the placebo nor the budesonide group did the
      geometric mean of PC(20) change significantly over the 9-month period. In
      contrast, a significant increase in PC(20) was noted in the symptomatic group as
      a result of the budesonide treatment. CONCLUSION: Our data have shown that
      budesonide inhaled regularly for 9 months did not cause a significant improvement
      in the BHR of adolescents with long-term asthma remission. This suggests that the
      mechanism underlying BHR in this clinical setting may be different from that in
      symptomatic asthma.

PMID- 11591552
TI  - Symptom-limited stair climbing as a predictor of postoperative cardiopulmonary
      complications after high-risk surgery.
AB  - STUDY OBJECTIVE: Thoracotomy, sternotomy, and upper abdominal laparotomy are
      associated with high rate of postoperative cardiopulmonary complications (POCs).
      We hypothesized that symptom-limited stair climbing predicts POCs after high-risk
      surgery. DESIGN: A prospective evaluation of 83 patients undergoing thoracotomy,
      sternotomy, and upper abdominal laparotomy surgery. METHODS: The 52 men and 31
      women completed symptom-limited stair climbing. A separate investigator, blinded
      to the number of flights of stairs climbed, assessed 30-day actual outcomes for
      POCs, including pneumonia, atelectasis, mechanical ventilation for > 48 h,
      reintubation, myocardial infarction, congestive heart failure, arrhythmia,
      pulmonary embolus, and death within 30 days of surgery. The operations performed
      included 31 lobectomies, 6 wedge resections, 3 pneumonectomies, 3 substernal
      thymectomies, 1 substernal thyroidectomy, 23 colectomies, 3 laparotomies, 7
      abdominal aortic aneurysm repairs, 5 esophagogastrectomies, and 1 nephrectomy.
      RESULTS: POCs occurred in 21 of 83 patients (25%) overall, in 9 of 44 patients
      undergoing thoracotomy/sternotomy (20%), and in 12 of 39 patients undergoing
      upper abdominal laparotomy (31%). Of those unable to climb one flight of stairs,
      89% developed a POC. No patient able to climb the maximum of seven flights of
      stairs had a POC. The inability to climb two flights of stairs was associated
      with a positive predictive value of 82% for the development of a POC. The number
      of days in the hospital postoperatively decreased with a patient's increased
      ability to climb stairs. CONCLUSIONS: Symptom-limited stair climbing offers a
      simple, inexpensive means to predict POCs after high-risk surgery.

PMID- 11591553
TI  - Spirometry in surgery for anterior mediastinal masses.
AB  - STUDY OBJECTIVES: To identify the impact of upright and supine spirometry (USS)
      on the choice of anesthesia and outcomes in patients undergoing surgery for
      anterior mediastinal masses (AMMs). DESIGN: Retrospective cohort study. SETTING:
      A referral, tertiary-care, military medical center. PATIENTS: We reviewed the
      records of all patients who underwent surgery for AMMs between June 1994 and
      December 2000 at Walter Reed Army Medical Center. Patients aged > or = 18 years
      who had "anterior mediastinal mass" listed as the preoperative diagnosis, which
      had been confirmed by a preoperative CT scan, and who had available preoperative
      spirometry data were included in our analysis. In cases in which surgery was
      performed more than once on the same individual, only data from the first
      operation were evaluated. MEASUREMENTS: Patient demographics, the results of
      pulmonary function testing, perioperative complications, type of anesthesia, type
      of surgery, and pathology were used in the evaluation. RESULTS: Thirty-seven
      patients (median age, 31 years; age range, 19 to 86 years) were included in the
      final analysis. There were 24 men and 13 women in this group. The mean (+/- SD)
      seated FVC and FEV(1) values for the group were 4.02 +/- 0.75 L (90.7 +/- 13.3%
      predicted) and 3.22 +/- 0.56 L 89.6 +/- 14.2% predicted. Twelve patients (32.4%)
      had USS ordered, and 10 patients (27.0%) had USS performed. USS was ordered
      significantly more frequently in younger and symptomatic patients (p = 0.022 and
      p = 0.005, respectively). Spirometry suggestive of possible upper airway
      obstruction was found in four patients. However, general anesthesia was used in
      all four patients without complications. Only two patients suffered perioperative
      complications. One of these patients had normal USS values but underwent surgery
      under local anesthesia nonetheless. CONCLUSIONS: The recommendation to perform
      USS prior to surgery on AMMs is based on anecdotal data. Our study found that the
      incidence of perioperative complications in surgery for AMMs is low. We also
      found that USS is not ordered in all patients preoperatively and that the results
      do not always alter the anesthetic technique when abnormal. One patient who
      experienced a perioperative complication had normal USS values. Larger studies
      are necessary to further evaluate the utility of USS in surgery for AMMs.

PMID- 11591554
TI  - Increased effective lung volume following lung volume reduction surgery in
      emphysema.
AB  - STUDY OBJECTIVES: Lung volume reduction surgery (LVRS) for emphysema has a
      variable effect on spirometry with improvement linked to increases in lung
      elastic recoil. The mechanism by which recoil increases following LVRS has not
      been described completely. This study examines preoperative and postoperative
      pulmonary function to describe a mechanism for changes in airflow obstruction.
      DESIGN: Change in pulmonary function following LVRS. Setting : Public teaching
      hospital in Australia. PATIENTS: Patients with severe emphysema and pulmonary
      function measurements made before and after LVRS. MEASUREMENTS: Routine pulmonary
      function testing performed with ventilated lung alveolar volume (VA) derived from
      the gas transfer measurement used as a proxy for the effective lung volume.
      RESULTS: Pulmonary function tests from 36 consecutive patients with measurements
      made at the same laboratory were analyzed. The mean FEV(1) was 29.1% predicted
      presurgery and increased following LVRS from 0.900 L (SD, 0.427 L) to 1.283 L
      (SD, 0.511 L; p < 0.0001) and TLC (143% predicted) decreased from 8.19 L (SD,
      1.492 L) to 7.07 L (SD, 1.52 L; p < 0.0001; n = 35). The mean VA increased by
      0.674 L (SD, 0.733 L) from 4.04 to 4.72 L (p < 0.0001; n = 34). The change in
      FEV(1) correlated well with the change in VA (r = 0.63). The change in FEV(1) in
      those patients whose VAs did not increase (n = 7) was not significant.
      CONCLUSIONS: The increase in VA reflects an increase of functional or ventilating
      lung volume and is associated with an improvement in spirometry following LVRS.

PMID- 11591555
TI  - Thorax and lung injuries arising from the two earthquakes in Turkey in 1999.
AB  - STUDY OBJECTIVE: To make a descriptive analysis of the frequency and the type of
      thorax and lung injuries among the casualties of the two devastating earthquakes
      that occurred in Turkey in 1999. DESIGN: Records of the hospitalized patients
      injured in the earthquakes were examined retrospectively. RESULTS: Among the
      total of 356 hospitalized patients, 21 (9.7%) in the Izmit earthquake and 6
      (7.6%) in the Duzce earthquake had thorax and lung injuries. Pneumothorax and rib
      fractures were the two most frequent pathologies and accounted for 50% and 33.3%
      of the injuries, respectively. CONCLUSION: Approximately 10% of the casualties of
      a great earthquake may be expected to have thorax and lung injuries, and
      traumatic chest diseases should be considered in planning the medical response
      strategies.

PMID- 11591556
TI  - Intraoperative photodynamic therapy after pleuropneumonectomy in patients with
      malignant pleural mesothelioma: dose finding and toxicity results.
AB  - OBJECTIVE: To determine the optimal administered dose of meta
      tetrahydroxyphenylchlorin (mTHPC) for intraoperative photodynamic therapy (IPDT)
      in resected malignant pleural mesothelioma (MPM). The primary objective of this
      combination treatment was to improve local tumor control. DESIGN: Phase I/II dose
      escalation study. SETTING: Two Dutch cancer centers. PATIENTS: The study included
      28 patients (2 women, 26 men), with pathologically confirmed MPM. The mean age
      was 57 years (age range, 37 to 68 years), and the World Health Organization
      performance score was 0 to 1. Epithelial mesotheliomas were found in 17 patients,
      a sarcomatous mesothelioma was found in 1 patient, and mixed epithelial
      sarcomatous mesotheliomas were found in 10 patients. METHODS: Patients were
      injected with 0.075 mg/kg (4 patients), 0.10 mg/kg (19 patients), or 0.15 mg/kg
      (5 patients) mTHPC 4 or 6 days before undergoing surgery and IPDT. Complete
      surgical resection (i.e., pleuropneumonectomy) was followed by integral
      illumination with monochromatic light of 652 nm (10 J/cm(2)). The real-time
      fluence rate measurements were performed using four isotropic detectors in the
      chest cavity to calculate the total light dose. RESULTS: Dose-limiting toxicity
      was reached at the level of 0.15 mg/kg mTHPC. Three patients died in the
      perioperative period, and one death was directly related to photodynamic therapy.
      Real-time dosimetry identified 12 patients in whom additional illumination had to
      be given to the diaphragmatic sinuses, which were unavoidably shielded during
      integral illumination. In two patients, illumination was cancelled due to the
      insufficient resectability of the tumor. The median survival time for all 28
      patients was 10 months. Local tumor control, 9 months after treatment, was
      achieved in 13 of the 26 patients treated with IPDT. CONCLUSION: IPDT using
      mTHPC, combined with a pleuropneumonectomy, resulted in local control of disease
      in 50% of the treated cases. The considerable toxicity associated with the
      procedure, however, precludes its recommendation for widespread use. Stricter
      patient selection and improvements of the IPDT technique may reduce the toxicity.

PMID- 11591557
TI  - Preoperative steroid therapy inhibits cytokine production in the lung parenchyma
      in asthmatic patients.
AB  - OBJECTIVES: During or after surgery, asthma attacks due to airway
      hyperresponsiveness (AHR) are likely to occur in patients with bronchial asthma.
      Preoperative administration of corticosteroid for prevention of perioperative
      asthma attacks is useful. We examined the mechanism of prevention of
      perioperative asthma attacks by the preoperative administration of corticosteroid
      in vitro. DESIGN: Five patients with asthma were treated with 20 mg of
      prednisolone orally for 2 preoperative days and 80 mg of methylprednisolone IV
      immediately before and after surgery. In another five patients without asthma, no
      steroids were administered. A noncarcinomatous part of the resected tissue from
      each patient with lung cancer was passively sensitized with the serum of an
      atopic patient. In the patients without asthma, the tissue was treated with or
      without dexamethasone, and then mite antigen was added. MEASUREMENTS: The culture
      supernatant and lung tissue were recovered, and the supernatant was assayed for
      histamine, leukotriene E(4) (LTE(4)), interleukin (IL)-5, and tumor necrosis
      factor (TNF)-alpha. Degranulation of mast cells was measured by tryptase staining
      of the lung tissue, and the expression of messenger RNA (mRNA) of IL-5 and TNF
      alpha was determined by the reverse transcriptase-polymerase chain reaction
      method. RESULTS: While preoperative administration of corticosteroid did not
      suppress the release of histamine and LTE(4) from the lungs of asthmatic
      patients, it completely suppressed IL-5 and TNF-alpha production at the mRNA
      level. The same results were obtained in lung tissues of nonasthmatic patients
      treated in vitro with dexamethasone. CONCLUSIONS: Our results suggest that
      corticosteroid treatment reduces AHR and prevents perioperative attacks of asthma
      primarily by suppressing the production of inflammatory cytokines.

PMID- 11591558
TI  - The effects of an inhaled beta(2)-adrenergic agonist on lower esophageal
      function: a dose-response study.
AB  - STUDY OBJECTIVES: Albuterol, a beta(2)-adrenergic agonist that is commonly used
      to treat asthma, reduces bronchial smooth muscle tone. The pharmacodynamics of
      inhaled albuterol on esophageal function were studied in healthy volunteers.
      DESIGN: A prospective, randomized, placebo-controlled, double-blind crossover
      design. SETTING: An academic medical center. PATIENTS: Nine healthy volunteers
      (five men, four women; age, 22 to 30 years). INTERVENTIONS: Albuterol (2.5 to 10
      mg) or placebo was given via nebulizer. Volunteers were studied at two sessions,
      1 week apart, using a 6-cm manometry assembly and a low-compliance
      pneumohydraulic pump. The percentage of lower esophageal sphincter (LES)
      relaxation, the frequency of transient LES relaxations (TLESRs), and the
      amplitude, duration, and propagation velocity of esophageal contractions were
      measured at 5 and 10 cm above the LES. Dependent measures were evaluated using
      two-way, repeated-measures analysis of variance. MEASUREMENTS AND RESULTS:
      Albuterol therapy reduced LES basal tone in a dose-dependent manner (baseline,
      17.0 +/- 2.6 mm Hg; at 10 mg, 8.9 +/- 2.1 mm Hg; p = 0.01). The frequency of
      TLESRs was not different from placebo (not significant). Albuterol reduced the
      amplitude of esophageal contractions at 5 cm above the LES (baseline, 72.5 +/-
      18.6 mm Hg; at 10 mg, 48.8 +/- 10.0 mm Hg; p<0.05). A significant reduction in
      esophageal body contractile amplitudes was noted at 10 cm (F[1,6] = 7.05;
      p<0.05). CONCLUSIONS: Inhaled albuterol reduced LES basal tone and contractile
      amplitudes in the smooth muscle esophageal body in a dose-dependent manner.
      Inhaled beta(2)-agonists may increase the likelihood of acid reflux in a subset
      of patients who receive cumulative dosing.

PMID- 11591559
TI  - Chronic aspiration without gastroesophageal reflux as a cause of chronic
      respiratory symptoms in neurologically normal infants.
AB  - OBJECTIVE: To describe 13 neurologically normal infants with chronic respiratory
      symptoms who had swallowing dysfunction with silent chronic aspiration without
      gastroesophageal reflux (GER) as the cause of their respiratory symptoms.
      BACKGROUND: Infants with neurologic disorders and infants with GER are known to
      have chronic respiratory symptoms. Isolated swallowing dysfunction and aspiration
      without GER in neurologically normal infants have not been widely reported.
      DESIGN: Retrospective chart review. SETTING: A tertiary pulmonary-care center at
      a children's hospital. PATIENTS: One hundred twelve otherwise healthy infants
      referred for respiratory symptoms who underwent esophageal pH studies and
      videofluoroscopic swallow studies (VSSs). METHODS: The records of infants
      referred between January 1997 and December 1999 to the Department of Pediatric
      Pulmonology who underwent 24-h esophageal pH monitoring and VSS as part of an
      evaluation for recurrent stridor and/or wheezing were reviewed. Significant GER
      was diagnosed if the percentage of time with esophageal pH < 4 was > 6%. Infants
      included in the study presented with recurrent respiratory symptoms, were born at
      term, were neurologically normal, had normal results of esophageal pH studies,
      but had abnormal results of VSSs (n = 13). RESULTS: All 13 infants presented with
      a variety of recurrent respiratory symptoms including wheezing and intermittent
      stridor. Ten of 13 infants had spitting and/or choking episodes with feeding. The
      mean (+/- SD) age at the onset of symptoms was 2.0 +/- 1.6 months, and the mean
      age at VSS was 5.9 +/- 3.4 months. All 13 infants had normal results of 24-h
      esophageal pH studies but had abnormal results for VSSs. All infants had evidence
      of swallowing dysfunction and direct silent aspiration of liquids with thin
      consistency. Six infants also were aspirating liquids with thick and/or semi
      thick consistencies. None of the infants had evidence of structural anomalies on
      esophagograms. Nine infants were treated with thickened food, and in four infants
      oral feedings were stopped. Three of these infants required nasojejunal feeding,
      and one infant required gastrostomy tube feeding. VSSs were repeated every 3
      months. In all infants, swallowing dysfunction resolved within 3 to 9 months. All
      infants tolerated the resumption of oral feeding. Videofluoroscopic documentation
      of the resolution of aspiration was followed by the resolution of respiratory
      symptoms in all infants. CONCLUSION: There is a subgroup of otherwise healthy
      infants, presenting with wheeze and/or stridor, who have isolated swallowing
      dysfunction and silent aspiration as the cause of their respiratory symptoms.

PMID- 11591560
TI  - Effect of acute myocardial infarction on cholesterol ratios.
AB  - OBJECTIVE: In patients with acute myocardial infarctions (MIs), cholesterol
      levels are no longer valid after 24 h from presentation because acute MI causes a
      rapid decline in serum levels of total cholesterol, low-density lipoprotein (LDL)
      cholesterol, and high-density lipoprotein (HDL) cholesterol. The objective of
      this study was to evaluate the effect of acute MI on the total cholesterol/HDL
      cholesterol ratio and the LDL cholesterol/HDL cholesterol ratio. METHODS: The
      study consisted of 45 patients who were admitted to the hospital with acute MIs.
      Serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, and
      triglycerides were determined on day 1 post-MI and day 4 post-MI. The total
      cholesterol/HDL cholesterol ratio and the LDL cholesterol/HDL cholesterol ratio
      were calculated. Serum lipid levels and cholesterol ratios were compared between
      day 1 post-MI and day 4 post-MI. RESULTS: From day 1 post-MI to day 4 post-MI,
      the mean (+/- SD) serum levels of total cholesterol (188.4 +/- 52.5 vs. 170.5 +/-
      57.2 mg/dL, respectively; p = 0.01), LDL cholesterol (120.3 +/- 48.9 vs. 105.9 +/
      43.0 mg/dL, respectively; p = 0.009), and HDL cholesterol (45.0 +/- 18.5 vs 39.3
      +/- 16.1 mg/dL, respectively; p < 0.001) decreased, but the mean serum level of
      triglycerides (119.2 +/- 81.2 vs 149.3 +/- 68.3 mg/dL, respectively; p = 0.006)
      increased. The cholesterol ratios, however, remained unchanged between day 1 post
      MI and day 4 post-MI. The total cholesterol/HDL cholesterol ratio was 4.59 +/-
      1.84 on day 1 post-MI and 4.67 +/- 1.77 on day 4 post-MI (change not
      significant). The LDL cholesterol/HDL cholesterol ratio was 2.96 +/- 1.58 on day
      1 post-MI and 2.99 +/- 1.44 on day 4 post-MI (change not significant).
      CONCLUSION: Acute MI does not affect the cholesterol ratios. Therefore, when the
      absolute levels of serum cholesterol are no longer valid (beyond 24 h after an
      MI), the cholesterol ratios still could be useful for cholesterol risk assessment
      in patients with acute MIs.

PMID- 11591561
TI  - Prognostic power of dobutamine echocardiography after uncomplicated acute
      myocardial infarction in the elderly.
AB  - STUDY OBJECTIVES: To assess the prognostic value of dobutamine-atropine stress
      echocardiography (DSE) after uncomplicated acute myocardial infarction (AMI) in
      elderly patients. DESIGN: We analyzed 59 consecutive patients (42 men) aged > or
      = 70 years (mean +/- SD age, 75 +/- 4 years) who underwent DSE within 10 days
      after uncomplicated AMI. DSE was carried out following the standard protocol.
      Five myocardial responses were considered: (1) negative, (2) sustained
      improvement of contractility, (3) biphasic response (initial improvement followed
      by worsening), (4) worsening of contractility in the infarcted area, and (5)
      worsening at a distance. RESULTS: Mean follow-up duration was 13 +/- 8 months.
      Twenty-one patients had an event: cardiac death (n = 5), myocardial infarction (n
      = 1), heart failure (n = 1), unstable angina (n = 10), and revascularization (n =
      4). Clinical and stress echocardiographic variables previously related to adverse
      prognosis were entered in Cox regression analysis, and the predictors of impaired
      outcome were inducible ischemia during DSE (hazard ratio [HR], 2.97; 95%
      confidence interval [CI], 1.77 to 4.99; p < 0.001) and resting wall motion score
      index (WMSI) > 1.6 (HR, 1.68; 95% CI, 1.02 to 2.77; p = 0.04). After excluding
      revascularization procedures and considering only spontaneous events, the
      following predictors were found: ischemia during DSE (HR, 2.95; 95% CI, 2.78 to
      3.12; p < 0.001) and resting WMSI > 1.6 (HR, 2.53; 95% CI, 1.30 to 4.93; p =
      0.006). CONCLUSIONS: Inducible ischemia during DSE within 10 days after
      uncomplicated AMI predicts an impaired outcome in the elderly.

PMID- 11591562
TI  - Effect of exercise training on postexercise oxygen uptake kinetics in patients
      with reduced ventricular function.
AB  - BACKGROUND: The time required for oxygen uptake (O(2)) to return to baseline
      level (recovery kinetics) is prolonged in patients with reduced ventricular
      function, and the degree to which it is prolonged is related to the severity of
      heart failure, markers of abnormal ventilation, and prognosis. In the present
      study, we sought to determine the effect of exercise training on O(2) recovery
      kinetics in patients with reduced ventricular function. METHODS: Twenty-four male
      patients with reduced ventricular function after a myocardial infarction were
      randomized to either a 2-month high-intensity residential exercise training
      program or to a control group. O(2) kinetics in recovery from maximal exercise
      were calculated before and after the study period and expressed as the slope of a
      single exponential relation between O(2) and time during the first 3 min of
      recovery. RESULTS: Peak O(2) increased significantly in the exercise group (19.4
      +/- 3.0 mL/kg/min vs 25.1 +/- 4.7 mL/kg/min, p < 0.05), whereas no change was
      observed in control subjects. The O(2) half-time in recovery was reduced slightly
      after the study period in both groups (108.7 +/- 33.1 to 102.1 +/- 50.5 s in the
      exercise group and 122.3 +/- 68.7 to 107.5 +/- 36.0 s in the control group);
      neither the change within or between groups was significant. The degree to which
      O(2) was prolonged in recovery was inversely related to measures of exercise
      capacity (peak O(2), watts achieved, and exercise time; r = - 0.48 to - 0.57; p <
      0.01) and directly related to the peak ventilatory equivalents for oxygen (r =
      0.59, p < 0.01) and carbon dioxide (r = 0.57, p < 0.01). CONCLUSION: Two months
      of high-intensity training did not result in a faster recovery of O(2) in
      patients with reduced ventricular function. This suggests that adaptations to
      exercise training manifest themselves only during, but not in, recovery from
      exercise.

PMID- 11591563
TI  - Effect of primary angioplasty on total or subtotal left main occlusion: analysis
      of incidence, clinical features, outcomes, and prognostic determinants.
AB  - BACKGROUND: Although acute left main coronary artery (LMCA) occlusion is a rare
      clinical entity, it carries a very high mortality rate. The purposes of this
      study were to evaluate the effect of primary angioplasty for a severely
      obstructed or totally occluded LMCA, and to determine the incidence, clinical
      features, outcome, and prognostic determinants in this clinical setting.
      MATERIALS AND METHODS: Between May 1993 and July 2000, a total of 740 patients
      with acute myocardial infarction underwent primary angioplasty in our hospital.
      Eighteen of 740 patients (2.4%) with a severely obstructed or totally occluded
      LMCA constituted the population of this study. RESULTS: Seventeen of 18 patients
      (94.4%) experienced pulmonary edema (including 14 patients in cardiogenic shock).
      Six patients (33.3%) sustained sudden death due to malignant ventricular
      tachyarrhythmias. Coronary angiography showed that there were variable grade flow
      of intercoronary collaterals in 12 patients (66.7%), a totally occluded LMCA in 8
      patients (44.4%), an incompletely occluded LMCA in 10 patients (55.6%), and a
      dominant right coronary artery (RCA) in 16 patients (88.9%). Primary angioplasty
      of the LMCA was performed with a 72.2% procedural success rate. Four patients
      (22.2%) received coronary artery bypass surgery after angioplasty. Six patients
      (33.3%) died in the hospital. Two patients died after discharge. Ten of 18
      patients (55.6%) survived in long-term follow-up (mean +/- SD, 44 +/- 14 months).
      Those patients who survived to be discharged had significantly higher combined
      coexisting incidence of intercoronary collaterals, dominant RCA, and incompletely
      occluded LMCA (100% vs 0.0%, p = 0.0006) than those patients who died in the
      hospital. CONCLUSIONS: Acute obstructive LMCA disease generally presented as
      pulmonary edema, cardiogenic shock, or sudden death. Only those who had combined
      coexistence of intercoronary collaterals, a dominant RCA, and an incompletely
      occluded LMCA could survive to be discharged. Our experience suggests that
      primary LMCA angioplasty is a feasible and effective procedure, and it may save
      lives in this clinical setting.

PMID- 11591564
TI  - Effects of dobutamine on critical capillary PO(2) and lactic acidosis threshold
      in patients with cardiovascular disease.
AB  - BACKGROUND: Muscle capillary PO(2) has been found to reach a minimal value, ie, a
      critical capillary PO(2), in the midrange of work capacity in patients with
      cardiovascular disease. However, it is not known if the critical capillary PO(2)
      can be influenced by a change in blood flow response to exercise. This study was
      carried out to determine the effect of changing the blood flow response to
      exercise, using low-dose infusion of dobutamine, on muscle end-capillary PO(2)
      (as approximated by femoral vein PO(2)), lactate concentration, oxygen uptake
      (O(2)), and the relation among these variables. METHODS: Eleven male patients
      with coronary artery disease performed an incremental exercise test on a cycle
      ergometer with and without continuous infusion of dobutamine, 6 microg/kg/min.
      Respiratory gas analysis was performed on a breath-by-breath basis; femoral vein
      blood was sampled every minute through a percutaneous catheter. RESULTS:
      Dobutamine increased resting O(2) and O(2) at the lactic acidosis threshold (LAT)
      but not peak O(2). The femoral vein PO(2) rapidly decreased toward a minimal
      value with increasing work rate (O(2)) irrespective of the infusion of
      dobutamine. After reaching its nadir (critical PO(2)), femoral vein lactate began
      to increase without further decrease in PO(2). Infusion of dobutamine
      significantly increased femoral vein resting PO(2) (27.4 +/- 4.9 mm Hg vs 32.5 +/
      3.8 mm Hg) and critical PO(2) (20.5 +/- 1.5 mm Hg vs 21.9 +/- 1.7 mm Hg), but
      not the PO(2) at peak O(2) (22.1 +/- 3.3 mm Hg vs 22.0 +/- 2.9 mm Hg).
      CONCLUSIONS: Infusion of dobutamine was found to raise the critical PO(2) and LAT
      but not peak O(2). These findings suggest that some of the acute increase in
      blood flow induced by dobutamine infusion benefits exercising muscle by
      increasing capillary PO(2), thereby delaying the onset of lactic acidosis.

PMID- 11591565
TI  - Plasma markers of endothelial dysfunction in pulmonary hypertension.
AB  - STUDY OBJECTIVES: To evaluate and to correlate endothelial cell dysfunction,
      using recently available plasma markers, with the magnitude of pulmonary artery
      pressure in patients with severe pulmonary hypertension (PH). DESIGN: Selected
      plasma markers of endothelial cell dysfunction were studied: nitric oxide (NO),
      thrombomodulin, tissue factor pathway inhibitor, and soluble endothelium,
      leukocyte, and platelet selectins (sE-, sL-, sP-selectins, respectively).
      SETTING: Padova University Hospital and Department of Pathology and Pharmacology,
      Loyola University of Chicago, Chicago, IL. PATIENTS: Fifteen patients had severe
      PH (four men and 11 women; mean age, 49.7 +/- 2.9 years: seven patients had
      primary pulmonary hypertension [PPH] and eight patients had secondary pulmonary
      hypertension [SPH]), and 20 patients were healthy control subjects. MEASUREMENT
      AND RESULTS: In patients with PH, sP- and sE-selectins were elevated, whereas sL
      selectin was lower in comparison with the selectin levels in control subjects.
      However, the differences between patients with PH and control subjects were
      significant only for sL-selectin (p < 0.0001) and sE-selectin (p < 0.03). The NO
      level was significantly lower in patients with PH compared with the NO level in
      control subjects (p < 0.01). No difference in tissue factor pathway inhibitor
      level was noted between control subjects and patients with PH. Only a weak
      correlation was found between thrombomodulin plasma levels and magnitude of
      systolic pulmonary artery pressure (r = -0.528, p < 0.05). CONCLUSIONS: Our data
      are in keeping with the evidence for significant endothelial cell dysfunction in
      patients with PH and the need for chronic anticoagulation believed to increase
      survival in these patients. In addition, these data seem to suggest a need for
      newer agents that are able to increase the antithrombotic endothelial function.

PMID- 11591566
TI  - Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during
      sleep.
AB  - OBJECTIVE: To identify the spectrum of respiratory disturbances during sleep in
      patients with obesity hypoventilation syndrome (OHS) and to examine the response
      of hypercapnia to treatment of the specific ventilatory sleep disturbances.
      DESIGNS AND METHODS: Twenty-three patients with chronic awake hypercapnia (mean
      [+/- SD] PaCO(2), 55 +/- 6 mm Hg) and a respiratory sleep disorder were
      retrospectively identified. Nocturnal polysomnography testing was performed, and
      flow limitation (FL) was identified from the inspiratory flow-time contour.
      Obstructive hypoventilation was inferred from sustained FL coupled with O(2)
      desaturation that was corrected with treatment of the upper airway obstruction.
      Central hypoventilation was inferred from sustained O(2) desaturation that
      persisted after the correction of the upper airway obstruction. Treatment was
      initiated, and follow-up awake PaCO(2) measurements were obtained (follow-up
      range, 4 days to 7 years). RESULTS: A variable number of obstructive sleep
      apneas/hypopneas (ie, obstructive sleep apnea-hypopnea syndrome [OSAHS]) were
      noted (range, 9 to 167 events per hour of sleep). Of 23 patients, 11 demonstrated
      upper airway obstruction alone (apnea-hypopnea/FL) and 12 demonstrated central
      sleep hypoventilation syndrome (SHVS) in addition to a variable number of OSAHS.
      Treatment aimed at correcting the specific ventilatory abnormalities resulted in
      correction of the chronic hypercapnia in all compliant patients (compliant
      patients: pretreatment, 57 +/- 6 mm Hg vs post-treatment, 41 +/- 4 mm Hg [p <
      0.001]; noncompliant patients: pretreatment, 52 +/- 6 mm Hg vs post-treatment, 51
      +/- 3 mm Hg; [difference not significant]). CONCLUSIONS: This study demonstrates
      that OHS encompasses a variety of distinct pathophysiologic disturbances that
      cannot be distinguished clinically at presentation. Sustained obstructive
      hypoventilation due to partial upper airway obstruction was demonstrated as an
      additional mechanism for OHS that is not easily classified as SHVS or OSAHS.

PMID- 11591567
TI  - Predicting sleep-disordered breathing in patients with cystic fibrosis.
AB  - STUDY OBJECTIVES: To examine predictors of sleep-disordered breathing in patients
      with cystic fibrosis (CF) and moderate-to-severe lung disease using a
      comprehensive evaluation of both sleep and daytime function. DESIGN: Cross
      sectional analysis of sleep studies, lung function, respiratory muscle strength,
      and evening and morning arterial blood gas measurements in patients with stable
      CF. A questionnaire addressing sleep quality was administered. Forward stepwise
      regression analysis was used to identify the parameters that best predict sleep
      related desaturation, hypercapnia, and respiratory disturbance. SETTING: Sleep
      investigation unit and lung function laboratory. PATIENTS: Thirty-two patients
      with CF and FEV(1) < 65% predicted, in stable clinical condition. Patients were
      aged 27 +/- 8 years (mean +/- 1 SD) with FEV(1) of 36 +/- 10% predicted, evening
      PaO(2) of 68 +/- 8 mm Hg, and PaCO(2) of 43 +/- 5 mm Hg. RESULTS: Evening PaO(2)
      (p < 0.0001) and morning PaCO(2) (p < 0.01) were predictive of the average
      minimum oxyhemoglobin saturation per 30-s epoch of sleep (r(2) = 0.74; p <
      0.0001). Evening PaO(2) (p < 0.001) was predictive of the rise in transcutaneous
      carbon dioxide (TcCO(2)) seen from non-rapid eye movement (NREM) to rapid eye
      movement (REM) sleep (r(2) = 0.37; p < 0.001). In addition, there was some
      relationship between expiratory respiratory muscle strength and the REM
      respiratory disturbance index (r(2) = 0.22; p < 0.01). CONCLUSION: Evening PaO(2)
      was found to contribute significantly to the ability to predict both sleep
      related desaturation and the rise in TcCO(2) from NREM sleep to REM sleep in this
      subgroup of patients with CF.

PMID- 11591568
TI  - The psychological impact of end-stage lung disease.
AB  - STUDY OBJECTIVES: End-stage lung disease is associated with poor quality of life
      and increased risk for psychological distress. Despite the significant number of
      individuals with end-stage lung diseases, the emotional health of these patients,
      as compared with those with other chronic organ diseases, is not well-known. The
      purpose of this article is to elucidate personality styles and the presence of
      psychopathology in a clinical sample of patients with end-stage lung disease
      presenting for possible lung transplantation. DESIGN: Cross-sectional survey.
      SETTING: Two academic medical center transplant programs. PARTICIPANTS: Two
      hundred forty-three consecutively referred transplant candidates. RESULTS:
      Cluster analysis of the Minnesota Multiphasic Personality Inventory (MMPI)-2
      indicated five different personality styles. The majority of patients evidenced
      mild somatic and depressive symptoms. Approximately one fourth of the sample
      exhibited marked anxiety and mood disturbances. A small cluster also evidenced
      features consistent with an antisocial personality style. CONCLUSIONS: Separate
      and distinct personality styles that could affect quality of life, the need for
      adjunct treatments, and medical compliance emerged from this sample of
      individuals with end-stage lung disease. Results are discussed in light of prior
      research on other end-stage organ conditions and in relation to personality and
      coping theories.

PMID- 11591569
TI  - Ipratropium bromide hydrofluoroalkane inhalation aerosol is safe and effective in
      patients with COPD.
AB  - STUDY OBJECTIVE: To compare the efficacy and safety of ipratropium bromide
      reformulated with the chlorofluorocarbon (CFC)-free propellant hydrofluoroalkane
      (HFA)-134a (ipratropium bromide HFA) to that of the marketed ipratropium bromide
      inhalation aerosol (containing CFC) in patients with COPD. DESIGN: This was a
      randomized, double-blind, parallel-group, placebo-controlled, multicenter trial.
      The primary efficacy parameter was acute bronchodilator response. The primary end
      points were peak change in FEV(1) from baseline and area under the response-time
      curve. SETTING: Thirty-one clinical centers in the United States participated in
      this project. PATIENTS: A total of 507 patients with moderate-to-severe COPD were
      randomized, and 444 patients completed the trial. INTERVENTIONS: Twelve weeks of
      treatment four times daily with one of the following: ipratropium bromide HFA, 42
      microg; ipratropium bromide HFA, 84 microg; HFA placebo; ipratropium bromide
      inhalation aerosol, 42 microg; or CFC placebo. MEASUREMENTS AND RESULTS: Patients
      in all active treatment groups had significant bronchodilator responses as shown
      by increases in mean FEV(1) from baseline of at least 15%. Bronchodilator
      response in all active treatment groups was also significantly more than their
      respective placebo treatments based on FEV(1), area under the time-response curve
      from 0 to 6 h, and peak response. FVC results were similar to those seen with
      FEV(1). There were no significant differences in adverse events, laboratory
      findings, or ECG findings among the treatment groups. CONCLUSIONS: Ipratropium
      bromide HFA, 42 and mgr;g, provided bronchodilation comparable to the marketed
      ipratropium bromide CFC, 42 and mgr;g, over 12 weeks of regular use.

PMID- 11591570
TI  - Predictors of extubation outcome in patients who have successfully completed a
      spontaneous breathing trial.
AB  - BACKGROUND: After patients recovering from respiratory failure have successfully
      completed a spontaneous breathing trial (SBT), clinicians must determine whether
      an artificial airway is still required. We hypothesized that cough strength and
      the magnitude of endotracheal secretions affect extubation outcomes. METHODS: We
      conducted a prospective study of 91 adult patients treated in medical-cardiac
      ICUs who were recovering from respiratory failure, had successfully completed an
      SBT, and were about to be extubated. A number of demographic and physiologic
      parameters were recorded with the patient receiving full ventilatory support and
      during the SBT, just prior to extubation. Cough strength on command was measured
      with a semiobjective scale of 0 to 5, and the magnitude of endotracheal
      secretions was measured as none, mild, moderate, or abundant by a single
      observer. In addition, patients were asked to cough onto a white card held 1 to 2
      cm from the endotracheal tube; if secretions were propelled onto the card, it was
      termed a positive white card test (WCT) result. All patients were then extubated
      from T-piece or continuous positive airway pressure breathing trials. If 72 h
      elapsed and patients did not require reintubation, they were defined as
      successfully extubated. RESULTS: Ninety-one patients with a mean (+/- SE) age of
      65.2 +/- 1.6 years, ICU admission APACHE (acute physiology and chronic health
      evaluation) II score of 17.7 +/- 0.7, and duration of mechanical ventilation of
      5.0 +/- 0.5 days were studied over 100 extubations. Sixteen patients could not be
      extubated, and 2 patients underwent two unsuccessful extubation attempts, for a
      total of 18 unsuccessful extubations. Age, severity of illness, duration of
      mechanical ventilation, oxygenation, rapid shallow breathing index, and vital
      signs during SBTs did not differ between patients with successful extubations vs
      patients with unsuccessful extubations. The WCT result was highly correlated with
      cough strength. Patients with weak (grade 0 to 2) coughs were four times as
      likely to have unsuccessful extubations, compared to those with moderate-to
      strong (grade 3 to 5) coughs (risk ratio [RR], 4.0; 95% confidence interval
      [CI],1.8 to 8.9). Patients with moderate-to-abundant secretions were more than
      eight times as times as likely to have unsuccessful extubations as those with no
      or mild secretions (RR, 8.7; 95% CI, 2.1 to 35.7). Patients with negative WCT
      results were three times as likely to have unsuccessful extubations as those with
      positive WCT results (RR, 3.0; 95% CI, 1.3 to 6.7). Poor cough strength and
      endotracheal secretions were synergistic in predicting extubation failure
      (Rothman synergy index, 3.7; RR, 31.9; 95% CI, 4.5 to 225.3). Patients with
      PaO(2)/fraction of inspired oxygen (P:F) ratios of 120 to 200 (receiving
      mechanical ventilation) were not less likely to be successfully extubated than
      those with P:F ratios of > 200, but those with hemoglobin levels < or = 10 g/dL
      were more than five times as likely to have unsuccessful extubations as those
      with hemoglobin levels > 10 g/dL. CONCLUSIONS: After patients recovering from
      respiratory failure have successfully completed an SBT, factors affecting airway
      competence, such as cough strength and amount of endotracheal secretions, may be
      important predictors of extubation outcomes. Also, a majority (89%) of medically
      ill patients with P:F ratios of 120 to 200 (four of five patients with P:F ratios
      from 120 to 150), values sometimes used to preclude weaning, were extubated
      successfully.

PMID- 11591571
TI  - Systemic inflammatory response syndrome, organ failure, and outcome in critically
      ill obstetric patients treated in an ICU.
AB  - STUDY OBJECTIVES: To determine the incidence of systemic inflammatory response
      syndrome (SIRS) and organ failure and to describe the outcomes in critically ill
      obstetric patients who have been treated in medical ICUs. DESIGN: Retrospective
      review. SETTING: A multidisciplinary ICU at a tertiary-care institution. METHODS:
      We collected data on 74 obstetric patients who were admitted consecutively to the
      ICU from January 1991 through December 1998. Acute physiology and chronic health
      evaluation (APACHE) II scores were calculated. A p value < 0.05 was considered to
      be significant. MEASUREMENTS AND RESULTS: Fifty-eight percent of patients were
      admitted to the ICU postpartum. Their mean (+/- SD) age was 25.9 +/- 7.0 years,
      and 64% were African American and 34% were white. Fifty percent had preexisting
      medical conditions. Their mean APACHE II score was 14.0 +/- 5.9, and their
      predicted mortality rate was 17.6%. The most common reason for admission was
      respiratory insufficiency. Preeclampsia was present in 38% of patients, and
      hemolytic anemia, elevated liver enzymes, and low platelet count syndrome were
      present in 7% of patients. SIRS developed in 59% of patients. Patients with SIRS
      had longer ICU stays (p = 0.0008). Organ failure developed in 65% of patients,
      and ARDS developed in 15% of patients. Invasive mechanical ventilation was
      required in 45% of patients, and pulmonary artery catheterization was required in
      35% of patients. The in-hospital mortality rate was 2.7%. There were five
      spontaneous abortions and eight perinatal deaths. CONCLUSIONS: The most common
      reason for admission to the ICU of critically ill obstetric patients was
      respiratory failure. Despite the severity of illness and the development of SIRS
      and organ failure in most patients, the mortality rate was low.

PMID- 11591572
TI  - Hospital readmission among long-term ventilator patients.
AB  - STUDY OBJECTIVES: Patients experiencing prolonged periods of in-hospital
      mechanical ventilation have been described as long-term ventilator (LTV)
      patients. The purpose of this study was to document the incidence of hospital
      readmission and to identify risk factors for readmission for LTV patients up to 6
      months after hospital discharge. DESIGN: This study was part of a larger
      prospective longitudinal descriptive study of posthospital outcomes for LTV
      patients. SETTING AND PARTICIPANTS: One hundred ninety-nine ICU patients admitted
      to a university medical center, Veterans Administration hospital, or small
      community hospital who required > 96 h of continuous in-hospital mechanical
      ventilation were enrolled. MEASUREMENTS AND RESULTS: Descriptive statistics,
      logistic regression, and survival analytic techniques were used. The 6-month
      hospital readmission rate was 38%. Readmission occurred most often within days 1
      to 60 days (mean, 39.2 days) posthospital discharge. Predictive variables for
      readmission were the following: length of the index hospital stay; length of the
      index mechanical ventilation; and the need for oxygen at hospital discharge.
      Using survival analysis, the age category of 66 to 71 years was statistically
      significant for the relative risk of readmission within the first 30 days of the
      index hospital discharge. CONCLUSIONS: LTV patients should be considered at risk
      for hospital readmission. Further study examining the impact of closer follow-up
      in the first 60 days posthospital discharge is necessary in order to determine
      whether there is a more effective way of reducing the risk of readmission for LTV
      patients.

PMID- 11591573
TI  - Contrast microbubbles improve diagnostic yield in ICU patients with poor
      echocardiographic windows.
AB  - OBJECTIVE: To determine the value of contrast echocardiographic studies in
      patients admitted to ICUs who have poor echocardiographic windows secondary to
      COPD, ventilator use, or inability to obtain optimal positioning for the
      echocardiogram. DESIGN: A prospective comparison study of technically difficult
      patients in the ICU. OUTCOME MEASURE: The total scores for the left ventricle
      (LV) in the two-chamber and four-chamber views were calculated at baseline and
      following injection of 1 to 2 mL of a contrast agent. The mean numbers of
      segments visualized in all patients at baseline and after injection of contrast
      agent were compared to assess the effect on improved visualization. RESULTS:
      Forty consecutive patients underwent echocardiography in the ICU for evaluation
      of LV function. Of these, 25 patients (63%) had poor visualization of the
      endocardium and required IV contrast agent. In these 25 patients, the average
      baseline segmental score was 4.5, compared to 11.6 in patients who received an IV
      contrast agent. Nineteen patients had an average baseline segmental score of 3.9
      and were deemed to have a nondiagnostic study. After administration of IV
      contrast, all patients converted to a diagnostic study, with an average score of
      11.6 segments visualized. CONCLUSIONS: Use of echocardiographic contrast agents
      in selected patients with poor baseline echocardiographic windows in the ICU
      setting significantly enhances segmental LV visualization and yielded 100%
      conversion from nondiagnostic to diagnostic studies.

PMID- 11591574
TI  - Inhibition of monocyte chemoattractant protein-1 expression in cytokine-treated
      human lung epithelial cells by thiazolidinedione.
AB  - STUDY OBJECTIVE: Several lung diseases are characterized by the presence of
      increased numbers of activated macrophages. The recruitment and activation of
      peripheral blood monocytes are potentially critical regulatory events for the
      control of pulmonary inflammation. The chemokine monocyte chemoattractant protein
      (MCP)-1 is a potent chemoattractant for monocytes. MCP-1 is produced by lung
      epithelial cells during the course of inflammatory lung diseases. In the present
      study, we examined the effects of a thiazolidinedione (TZD), which is used to
      improve the insulin resistance of individuals with diabetes mellitus, on MCP-1
      expression in a human lung epithelial cell line, A549. MEASUREMENTS AND RESULTS:
      In A549 cells, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha
      induced endogenous MCP-1 protein secretion and messenger RNA expression. The TZD
      inhibited the increase of MCP-1 secretion by IL-1beta and TNF-alpha treatment.
      The TZD inhibited the expression of MCP-1 messenger RNA with IL-1beta treatment,
      but not with TNF-alpha treatment. This observation was confirmed by the results
      of a monocyte chemotactic assay. The transcriptional activity of human MCP-1
      promoter in A549 cells paralleled the endogenous messenger RNA expression by
      cytokines and TZD treatment. CONCLUSIONS: Our findings indicated that the
      suppression of the expression of MCP-1 could be accomplished by TZD treatment,
      raising the possibility that TZD may be of therapeutic value in several lung
      diseases in which MCP-1 plays an important role.

PMID- 11591575
TI  - Initial evidence of endothelial cell apoptosis as a mechanism of systemic
      capillary leak syndrome.
AB  - BACKGROUND: Systemic capillary leak syndrome (SCLS) is a rare disorder of unknown
      etiology that is characterized by acute recurrent attacks of hypovolemic shock
      commonly following an inflammatory stimulus such as a viral illness. Prophylactic
      therapy is generally ineffective, and the outcome is frequently fatal. METHODS:
      In order to investigate the cellular mechanisms leading to SCLS, we examined the
      effects of sera from two patients with active SCLS on microvascular endothelial
      cell apoptosis in vitro. Apoptosis was determined by morphologic criteria, DNA
      fragmentation, annexin V stain, and by a quantitative photometric assay. The
      apoptotic pathway was investigated by Western blot of endothelial cells lysate
      after exposure to SCLS sera. RESULTS: The sera from patients with active SCLS
      mediated profound apoptosis of microvascular endothelial cells shortly after
      exposure. The exposed microvascular endothelial cells underwent immediate
      apoptosis as evidenced by morphologic changes, plasma membrane phosphatidylserine
      exposure, and by DNA fragmentation. Increased Bax/Bcl-2 ratio in endothelial
      cells exposed to SCLS sera was observed and suggested an oxidation injury as the
      possible mechanism for endothelial apoptosis. This potential mechanism was
      further explored by measuring intracellular reactive oxygen species (ROS)
      following SCLS serum exposure. Sera from both patients caused marked increases in
      ROS, initially detectable at 1 h and persisted for at least 12 h, with control
      serum from healthy subjects showing no effect on basal endothelial cell ROS
      concentrations. CONCLUSION: Components from the sera of patients with active
      systemic capillary leak syndrome in contrast to healthy subject sera mediate
      early and extensive endothelial apoptosis in vitro that is associated with
      oxidation injury. These data represent compelling initial evidence for oxidation
      induced apoptosis as a likely mechanism for endothelial injury leading to SCLS.

PMID- 11591576
TI  - Acoustic imaging of the human chest.
AB  - STUDY OBJECTIVES: A novel method for acoustic imaging of the human respiratory
      system is proposed and evaluated. DESIGN: The proposed imaging system uses
      simultaneous multisensor recordings of thoracic sounds from the chest wall, and
      digital, computer-based postprocessing. Computer simulations and recordings from
      a life-size gelatin model of the human thorax are used to evaluate the system in
      vitro. Spatial representations of thoracic sounds from 8-microphone and 16
      microphone recordings from five subjects (four healthy male adults and one child
      with lung consolidation) are used to evaluate the system in vivo. RESULTS:
      Results of the in vitro studies show that sound sources can be imaged to within 2
      cm, and that the proposed algorithm is reasonably robust with respect to changes
      in the assumed sound speed within the imaged volume. The images from recordings
      from the healthy volunteers show distinct patterns for inspiratory breath sounds,
      expiratory breath sounds, and heart sounds that are consistent with the assumed
      origin of the respective sounds. Specifically, the images support the concept
      that inspiratory sounds are produced predominantly in the periphery of the lung
      while expiratory sounds are generated more centrally. Acoustic images from the
      subject with lung consolidation differ substantially from the images of the
      healthy subjects, and localize the abnormality. CONCLUSIONS: Acoustic imaging
      offers new perspectives to explore the acoustic properties of the respiratory
      system and thereby reveal structural and functional properties for diagnostic
      purposes.

PMID- 11591577
TI  - Invasive arterial BP monitoring in trauma and critical care: effect of variable
      transducer level, catheter access, and patient position.
AB  - OBJECTIVES: (1) To determine the validity of current recommendations for direct
      arterial BP measurement that suggest that the transducer (zeroed to atmosphere)
      be placed level with the catheter access regardless of subject positioning: and
      (2) to investigate the effect of transducer level, catheter access site, and
      subject positioning on direct arterial BP measurement. DESIGN: Prospective,
      controlled laboratory study. SETTING: Large animal laboratory. SUBJECTS: Five
      Yorkshire pigs. INTERVENTIONS: Anesthetized animals had 16F catheters placed at
      three access sites: aortic root, femoral artery, and distal hind limb. Animals
      were placed in supine, reverse Trendelenburg 35 degrees, and Trendelenburg 25
      degrees positions with a transducer placed level to each access site while in
      every position. MEASUREMENTS AND MAIN RESULTS: For each transducer level, five
      systolic and diastolic pressures were measured and used to calculate five
      corresponding mean arterial pressures (MAPs) at each access site. When
      transducers were at the aortic root, MAP corresponding to aortic root pressure
      was obtained in all positions regardless of catheter access site. When
      transducers were moved to the level of catheter access, as current
      recommendations suggest, significant errors in aortic MAP occurred in the reverse
      Trendelenburg position. The same trend for error was noted in the Trendelenburg
      position but did not reach statistical significance. CONCLUSIONS: (1) Current
      recommendations that suggest placing the transducer at the level of catheter
      access regardless of patient position are invalid. Significant errors occur when
      subjects are in nonsupine positions. (2) Valid determination of direct arterial
      BP is dependent only on transducer placement at the level of the aortic root, and
      independent of catheter access site and patient position.

PMID- 11591578
TI  - Autofluorescence bronchoscopy improves staging of radiographically occult lung
      cancer and has an impact on therapeutic strategy.
AB  - BACKGROUND: The ability of conventional CT scans and fiberoptic bronchoscopy to
      localize and properly stage radiographically occult lung cancer (ROLC) in the
      major airways is limited. High-resolution CT (HRCT) scanning and autofluorescence
      bronchoscopy (AFB) may improve the assessment of ROLC before the most appropriate
      therapy can be considered. PATIENTS AND METHODS: We prospectively studied 23
      patients with ROLC, who were referred for intraluminal bronchoscopic treatment
      (IBT) with curative intent. Additional staging with HRCT and AFB was performed
      prior to treatment. Twenty patients were men, 9 patients had first primary
      cancers, and 14 patients had second primary cancers or synchronous cancers.
      RESULTS: HRCT scanning showed that 19 patients (83%) had no visible tumor or
      enlarged lymph nodes. With AFB, only 6 of the 19 patients (32%) proved to have
      tumors < or = 1 cm(2) with visible distal margins. They were treated with IBT. In
      the remaining 13 patients, abnormal fluorescence indicated more extensive tumor
      infiltration than could be seen with conventional bronchoscopy alone. Six
      patients underwent radical surgery for stage T1-2N0 (n = 5) and stage T2N1 (n =
      1) tumors. Specimens showed that tumors were indeed more invasive than initially
      expected. The remaining seven patients technically did not have operable
      conditions, so they were treated with external irradiation (n = 4) and IBT (n =
      3). The range for the time of follow-up for all patients has been 4 to 58 months
      (median, 40 months). The follow-up data underscore the correlation between
      accurate tumor staging and survival. CONCLUSIONS: Our data showed that 70% of
      patients presenting with ROLC had a more advanced cancer than that initially
      diagnosed, which precludes IBT with curative intent. Additional staging with HRCT
      and AFB enabled better classification of true occult cancers. Our approach
      enabled the choice of the most appropriate therapy for each individual patient
      with ROLC.

PMID- 11591579
TI  - Virtual reality bronchoscopy simulation: a revolution in procedural training.
AB  - BACKGROUND: In the airline industry, training is costly and operator error must
      be avoided. Therefore, virtual reality (VR) is routinely used to learn manual and
      technical skills through simulation before pilots assume flight responsibilities.
      In the field of medicine, manual and technical skills must also be acquired to
      competently perform invasive procedures such as flexible fiberoptic bronchoscopy
      (FFB). Until recently, training in FFB and other endoscopic procedures has
      occurred on the job in real patients. We hypothesized that novice trainees using
      a VR skill center could rapidly acquire basic skills, and that results would
      compare favorably with those of senior trainees trained in the conventional
      manner. METHODS: We prospectively studied five novice bronchoscopists entering a
      pulmonary and critical care medicine training program. They were taught to
      perform inspection flexible bronchoscopy using a VR bronchoscopy skill center;
      dexterity, speed, and accuracy were tested using the skill center and an
      inanimate airway model before and after 4 h of group instruction and 4 h of
      individual unsupervised practice. Results were compared to those of a control
      group of four skilled physicians who had performed at least 200 bronchoscopies
      during 2 years of training. Student's t tests were used to compare mean scores of
      study and control groups for the inanimate model and VR bronchoscopy simulator.
      Before-training and after-training test scores were compared using paired t
      tests. For comparisons between after-training novice and skilled physician
      scores, unpaired two-sample t tests were used. RESULTS: Novices significantly
      improved their dexterity and accuracy in both models. They missed fewer segments
      after training than before training, and had fewer contacts with the bronchial
      wall. There was no statistically significant improvement in speed or total time
      spent not visualizing airway anatomy. After training, novice performance equaled
      or surpassed that of the skilled physicians. Novices performed more thorough
      examinations and missed significantly fewer segments in both the inanimate and
      virtual simulation models. CONCLUSION: A short, focused course of instruction and
      unsupervised practice using a virtual bronchoscopy simulator enabled novice
      trainees to attain a level of manual and technical skill at performing diagnostic
      bronchoscopic inspection similar to those of colleagues with several years of
      experience. These skills were readily reproducible in a conventional inanimate
      airway-training model, suggesting they would also be translatable to direct
      patient care.

PMID- 11591580
TI  - Aortic intramural hematoma: an increasingly recognized and potentially fatal
      entity.
AB  - Aortic intramural hematoma (IMH) is related to but is pathologically distinct
      from aortic dissection. In this potentially lethal entity, there is hemorrhage
      into the aortic media in the absence of an intimal tear. Although intimal
      disruption is not present, the prognosis is similar to that of classic aortic
      dissection; therefore, early diagnosis is critical. In this review, symptoms and
      prognosis of aortic IMH are discussed, as well as current diagnostic techniques
      and therapy.

PMID- 11591581
TI  - Treatment of ARDS.
AB  - Improved understanding of the pathogenesis of acute lung injury (ALI)/ARDS has
      led to important advances in the treatment of ALI/ARDS, particularly in the area
      of ventilator-associated lung injury. Standard supportive care for ALI/ARDS
      should now include a protective ventilatory strategy with low tidal volume
      ventilation by the protocol developed by the National Institutes of Health ARDS
      Network. Further refinements of the protocol for mechanical ventilation will
      occur as current and future clinical trials are completed. In addition, novel
      modes of mechanical ventilation are being studied and may augment standard
      therapy in the future. Although results of anti-inflammatory strategies have been
      disappointing in clinical trials, further trials are underway to test the
      efficacy of late corticosteroids and other approaches to modulation of
      inflammation in ALI/ARDS.

PMID- 11591582
TI  - Hypoplastic left-heart syndrome: the first description of the pathophysiology in
      1851; translation of a publication by Dr. Bardeleben from Giessen, Germany.

PMID- 11591583
TI  - A 12-year-old girl with dyspnea and a normal chest radiographic finding.
      Hypersensitivity pneumonitis.

PMID- 11591584
TI  - Bacterial/viral filtration: let the breather beware!
AB  - Most clinicians believe that any device that is marketed as a "bacterial/viral
      filter" must necessarily be capable of capturing any individual bacteria or
      viruses that might be suspended within inhaled or exhaled gases. We were
      surprised to discover that this is, by no means, a justifiable assumption. This
      article describes testing methods that manufacturers employ to generate the often
      misleading efficiency specifications that are claimed for some of these devices.
      We discuss articles that have documented the presence of airborne pathogens in
      the effluent of a ventilator circuit, and characterize the attributes that a
      competent filter must exhibit if it is to succeed in protecting patients and
      caregivers from incidental exposure to bacteria, viruses, aerosolized drugs, and
      endotoxins. This article continues with a discussion of the numbers of particles
      that are commonly produced with commercially available pneumatic nebulizers, the
      comparative performance characteristics of filters and heat/moisture exchanging
      filters (HMEFs), and the success or failure of various brands of HMEFs to comply
      with the guidelines recently developed by the Centers for Disease Control and
      Prevention for the management of patients who are harboring active tuberculosis.
      The presentation concludes with a description of the standards that apply to any
      filter that classifies as a high-efficiency particulate aerosol (HEPA) device,
      and demonstrates that the performance of filters/HMEFs in common clinical use can
      range from approximately 1/50th to > 30-fold the efficiency of a HEPA-grade
      device. Those who frequent the bedside of patients receiving ventilation might
      unwittingly be placing themselves at considerable risk of exposure to infectious
      microaerosols, but methods are available to dramatically decrease those risks.

PMID- 11591585
TI  - Top ten list in sepsis.

PMID- 11591586
TI  - Diffuse pulmonary nodular infiltrates in a renal transplant recipient. Metastatic
      pulmonary calcification.

PMID- 11591587
TI  - First experience with fiberoptically directed wire-guided endobronchial blockade
      in severe pulmonary bleeding in an emergency setting.
AB  - We report the first use of a new wire-guided endobronchial blocker in a critical
      respiratory situation caused by localized pulmonary bleeding. During emergency
      management, it became increasingly difficult to ventilate a multiple-trauma
      patient with a conventional single-lumen tube because of massive bleeding through
      the bronchus of the left lower lobe. Using the Arndt endobronchial blocker set
      (William Cook Europe A/S; Bjaeverskor, Denmark), we were able to prevent the
      spread of hemorrhaging and achieved effective ventilation and marked improvement
      in gas exchange. This new device allows the effective blockade of an isolated
      lobe under direct bronchoscopy to buy time for further intervention.

PMID- 11591588
TI  - Endobronchial foreign body extraction: a new interventional approach.
AB  - Endobronchial foreign bodies are often difficult to diagnose as the cause of
      obstructive pneumonias and atelectasis, but once discovered, they can generally
      be removed, leading to immediate and dramatic resolution of symptoms. The use of
      flexible fiberoptic and rigid bronchoscopy to extract foreign bodies is well
      known. Thoracotomy is generally reserved as a last resort due to the inherent
      risks of the procedure. We describe a new technique for foreign body removal
      utilizing steerable hydrophilic guidewires, standard sheaths, and a snare device
      commonly utilized in intravascular foreign body retrieval.

PMID- 11591589
TI  - Primary pulmonary plasmacytoma: a case report.
AB  - Most extramedullary plasmacytomas are associated with the upper respiratory
      tract. Primary pulmonary plasmacytomas are rare, and the treatment is surgical
      excision. This malignancy advances to multiple myeloma in a minority of patients.
      The patient in our case report is the first to experience renal failure due to
      hematologic monoclonal gammopathy. Postoperatively, serum protein electrophoresis
      reverted to normal.

PMID- 11591590
TI  - Pulmonary edema associated with hyperbaric oxygen therapy.
AB  - We report three cases of pulmonary edema associated with hyperbaric oxygen
      therapy, including one fatality. All three patients had cardiac disease and
      reduced left ventricular (LV) ejection fractions (EFs). Two patients had
      diabetes, and one patient had severe aortic stenosis. Hyperbaric oxygen therapy
      may contribute to pulmonary edema by increasing LV afterload, increasing LV
      filling pressures, increasing oxidative myocardial stress, decreasing LV
      compliance by oxygen radical-mediated reduction in nitric oxide, altering cardiac
      output between the right and left hearts, inducing bradycardia with concomitant
      LV dysfunction, increasing pulmonary capillary permeability, or by causing
      pulmonary oxygen toxicity. We advise caution in the use of hyperbaric oxygen
      therapy in patients with heart failure or in patients with reduced cardiac EFs.

PMID- 11591591
TI  - Stress thallium-201 myocardial scintigraphy in patients with complete occlusion
      of the left main coronary artery.
AB  - Complete occlusion (CO) of the left main coronary artery (LMCA) is a rare but
      often fatal condition. The diagnosis is frequently missed because the signs and
      symptoms are often obscure and diverse. We describe three patients with CO-LMCA
      who showed unusual myocardial scintigraphic findings. The patients had extensive
      right-to-left collateral channels and decreased uptake and washout rates at the
      basal anterior and anterolateral portions of the heart wall during stress
      thallium-201 scintigraphy. The basal anterior to anterolateral portion of the
      heart wall is the most distant from the collateral artery and should be the most
      ischemic area shown during exercise, resulting in this scintigraphic pattern.
      This scintigraphic finding may be useful for the noninvasive diagnosis of CO
      LMCA.

PMID- 11591592
TI  - Stenting to reverse left ventricular ischemia due to left main coronary artery
      compression in primary pulmonary hypertension.
AB  - Angina is a common symptom of severe pulmonary hypertension. Although many
      theories for the source of this pain have been proposed, right ventricular
      ischemia is the one most commonly accepted as the cause. We report on two
      patients with primary pulmonary hypertension who had angina with normal activity
      or on provocation. One patient had severe left ventricular dysfunction. Both were
      found to have severe ostial stenosis of the left main coronary artery as a result
      of compression from a dilated pulmonary artery. Both patients underwent stenting
      of the left main coronary artery with excellent angiographic results, and
      complete resolution of the signs and symptoms of angina and left ventricular
      ischemia. Left ventricular ischemia due to compression of the left main coronary
      artery may be a much more common mechanism of angina and left ventricular
      dysfunction in patients with pulmonary hypertension than previously acknowledged.
      Stenting of the coronary artery can be done safely with the resolution of these
      symptoms.

PMID- 11591593
TI  - Multiple coronary artery-left ventricular fistulas associated with hereditary
      hemorrhagic telangiectasia.
AB  - Coronary artery-left ventricular (LV) fistulas are extremely rare and can cause
      myocardial ischemia from coronary steal. We describe an elderly woman who
      presented with unstable angina from multiple and extensive coronary artery-LV
      fistulas. She also had clinical features suggestive of hereditary hemorrhagic
      telangiectasia (HHT). Association of coronary artery-LV fistulas with HHT has not
      been reported and can pose a management dilemma in view of the risks of extensive
      cardiopulmonary surgery and potential complications of myocardial ischemia,
      stroke, and brain abscess.

PMID- 11591594
TI  - Rescue percutaneous coronary intervention immediately following coronary artery
      bypass grafting.
AB  - Perioperative graft failure after coronary artery bypass graft (CABG) can result
      in acute myocardial infarction with dire clinical consequences. We report a case
      of rescue percutaneous coronary intervention immediately after unsuccessful CABG.
      This approach salvaged the patient from cardiogenic shock and should be
      recognized as a viable alternative to immediate reoperation for certain patients.

PMID- 11591595
TI  - Lung biopsy in pulmonary veno-occlusive disease.

PMID- 11591596
TI  - Inflammation and acute exacerbations of chronic bronchitis.

PMID- 11591597
TI  - Percutaneous dilational tracheostomy vs. open tracheostomy.

PMID- 11591598
TI  - Negative fluid balance as predictor of mortality.

PMID- 11591599
TI  - Does omentoplasty preclude cardiac retransplantation?

PMID- 11591600
TI  - End-of-life literature.

PMID- 11591602
TI  - Pleas from a pulmonary rehabilitation patient.

PMID- 11591601
TI  - Oxygen in costs of COPD treatment.

PMID- 11591605
TI  - Report from the 93rd Cardiovascular and Renal Drugs Advisory Committee Meeting,
      August 9-10, 2001.

PMID- 11591606
TI  - Off-pump coronary bypass surgery: in search of an identity.

PMID- 11591607
TI  - Angiotensin II induces circadian gene expression of clock genes in cultured
      vascular smooth muscle cells.
AB  - BACKGROUND: Daily rhythms of mammalian physiology and endocrinology are regulated
      by circadian pacemakers. The master circadian pacemaker resides in the
      suprachiasmatic nucleus, which is located in the hypothalamus of the brain, but
      circadian oscillators also exist in peripheral tissues. Because many studies have
      demonstrated apparent circadian variations in the frequency of cardiovascular
      disorders, it is of great interest to investigate a possible relation between
      circadian gene expression and cardiovascular function. We examined whether a
      circadian oscillation system exists in the aorta and/or in cultured vascular
      smooth muscle cells (VSMCs). METHODS AND RESULTS: The mRNA levels of clock genes
      were assayed by northern blot analysis. The mouse aorta showed a clear circadian
      oscillation in the expression of mPer2, dbp, and Bmal1. Brief treatment of VSMCs
      with angiotensin II induced a robust increase in mPer2 gene expression, followed
      by a marked reduction in mPer2 mRNA levels and subsequent synchronous cycling of
      mPer2, dbp, and Bmal1 mRNAs. The induction of mPer2 in VSMCs by angiotensin II
      was completely abolished by treatment with CV11947, a specific angiotensin II
      type1 receptor antagonist. CONCLUSIONS: The present results demonstrate that the
      aorta and VSMCs possess a circadian oscillation system which is comparable to
      that of the suprachiasmatic nucleus and that the circadian gene expression in
      VSMCs is induced by angiotensin II through the angiotensin II type1 receptor. Our
      in vitro system will provide a useful tool to further analyze the physiological
      significance of the peripheral clock in cardiovascular function.

PMID- 11591608
TI  - Activation of barium-sensitive inward rectifier potassium channels mediates
      remote dilation of coronary arterioles.
AB  - BACKGROUND: Conducted vasodilation seems to be critical for the functional
      distribution of blood flow in the skeletal muscle microcirculation. However, this
      vasoregulatory phenomenon has not been documented in the coronary
      microcirculation, and its underlying mechanism remains elusive. Because potassium
      ions are potent metabolic vasodilators in the heart, by activating vascular
      inward rectifier K(+) (K(ir)) channels, we tested the hypothesis that coronary
      arterioles exhibit remote vasodilation through activation of this type of
      channel. METHODS AND RESULTS: Porcine coronary arterioles were isolated,
      cannulated, and pressurized for in vitro study. Vessels dilated concentration
      dependently to extraluminal KCl (5 to 20 mmol/L), bradykinin, adenosine,
      pinacidil, and sodium nitroprusside. A K(ir) channel blocker, BaCl(2) (30
      micromol/L), inhibited vasodilatory responses to KCl and bradykinin but not to
      adenosine, pinacidil, or nitroprusside. In a flow chamber, localized
      administration of bradykinin, adenosine, and KCl to the downstream end of the
      arterioles caused approximately 80% dilation at the site of drug application
      (local site) and also produced 30% to 60% dilation at the upstream end of
      arterioles (remote site). Nitroprusside produced a similar dilation at the local
      site but failed to initiate remote vasodilation. In the presence of Ba(2+),
      adenosine still dilated the local site, but the local dilations to bradykinin and
      KCl and the remote dilations to adenosine, bradykinin, and KCl were inhibited.
      CONCLUSIONS: We demonstrated that some modes of local vasodilation can be
      conducted to remote sites in coronary arterioles and that local and remote
      dilations can occur through different vasodilatory mechanisms. Activation of
      K(ir) channels seems critical for some agonist-induced local vasodilations and
      also for the initiation and/or transmission of signals causing remote
      vasodilation.

PMID- 11591609
TI  - In vivo blockade of tumor necrosis factor-alpha accelerates functional
      endothelial recovery after balloon angioplasty.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF) is expressed locally in arteries at
      sites of balloon injury. In vitro studies have shown that TNF inhibits cell cycle
      progression and induces apoptosis in endothelial cells. Accordingly, we performed
      a series of experiments to test the hypothesis that inhibiting TNF could
      accelerate endothelial recovery after angioplasty. METHODS AND RESULTS: TNF
      soluble receptor (TNFsr) has been shown to neutralize the actions of TNF in vitro
      and in vivo. Sprague-Dawley rats received TNFsr versus control IgG through an
      intraperitoneal injection. De-endothelializing balloon injury was then performed,
      and animals were killed after 1 week to evaluate re-endothelialization (Evans
      blue dye staining) and after 2 weeks to evaluate re-endothelialization and
      endothelial function. At both time points, blockade of TNF using TNFsr resulted
      in an increase in re-endothelialization, as measured as absolute area and percent
      area re-endothelialized. TNFsr also accelerated functional endothelial recovery,
      which manifest as an increase in nitric oxide production. Neointimal thickening
      was also shown inhibited. CONCLUSIONS: In vivo blockade of TNF accelerates
      functional endothelial recovery after barotraumatic de-endothelializing injury.
      These findings suggest that locally expressed TNF acts to inhibit functional
      endothelial recovery after angioplasty and that transient blockade of TNF may
      improve the long-term success of angioplasty.

PMID- 11591610
TI  - Multimodal fetal transesophageal echocardiography for fetal cardiac intervention
      in sheep.
AB  - BACKGROUND: The overall performance of available mechanical intravascular
      ultrasound catheters for fetal transesophageal echocardiography during fetoscopic
      fetal cardiac interventions in sheep has been limited by radioelectronic
      interference, low system frame rates, and low acoustic outputs. Therefore, a more
      reliable device is desired for human fetoscopic surgical procedures. METHODS AND
      RESULTS: We assessed the potential of a newly available 10-French phased-array
      intravascular ultrasound catheter for multimodal fetal transesophageal
      echocardiography in 5 fetal sheep between 78 and 98 days of gestation (term, 145
      to 150 d). The intravascular ultrasound catheter was easily inserted through the
      mouth into the esophagus in all 5 sheep fetuses (mean weight, 600 g), and it
      permitted high-quality 2D imaging of the fetal heart in vertical imaging planes
      that were validated by MRI. Color Doppler and pulsed Doppler imaging permitted
      clear assessment of fetal cardiovascular flows and recording of velocity-time
      integral tracings of the fetal heart and great vessels. The vertical imaging
      planes were particularly useful to demonstrate interventional material inside the
      fetal heart and great vessels. CONCLUSIONS: Our early experience with the phased
      array intravascular ultrasound catheter indicates that multimodal fetal
      transesophageal echocardiography has now become possible in these smallest of
      patients.

PMID- 11591611
TI  - Early outcome after off-pump versus on-pump coronary bypass surgery: results from
      a randomized study.
AB  - BACKGROUND: The use of cardiopulmonary bypass during coronary artery bypass
      surgery (CABG) has been associated with substantial morbidity. The recent
      introduction of cardiac stabilizers facilitates CABG without cardiopulmonary
      bypass (off-pump CABG), but it is unknown whether cardiac outcome after off-pump
      surgery is similar to that for the on-pump procedure. METHODS AND RESULTS: In a
      multicenter trial, 281 patients (mean age 61 years, SD 9 years) were randomly
      assigned to off-pump or on-pump CABG. In-hospital results and cardiac outcome and
      quality of life after 1 month are presented. Cardiac outcome was defined as
      survival free of stroke, myocardial infarction, and coronary reintervention. The
      mean numbers of distal anastomoses per patient were 2.4 (SD 1.0) and 2.6 (SD 1.1)
      in the off-pump and on-pump groups, respectively. Completeness of
      revascularization was similar in both groups. Blood products were needed during
      3% of the off-pump procedures and 13% of the on-pump procedures (P<0.01). Release
      of creatine kinase muscle-brain isoenzyme was 41% less in the off-pump group
      (P<0.01). Otherwise, no differences in complications were found postoperatively.
      Off-pump patients were discharged 1 day earlier. At 1 month, operative mortality
      was zero in both groups, and quality of life had improved similarly. In both
      groups, 4% of the patients had recurrent angina. The proportions of patients
      surviving free of cardiovascular events were 93.0% in the off-pump group and
      94.2% in the on-pump group (P=0.66). CONCLUSIONS: In selected patients, off-pump
      CABG is safe and yields a short-term cardiac outcome comparable to that of on
      pump CABG.

PMID- 11591612
TI  - Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human
      endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A
      reductase inhibitor therapy.
AB  - BACKGROUND: Elevated oxidative stress and superoxide anion formation in vascular
      cells could promote conversion of LDL to atherogenic oxidized LDL (oxLDL),
      contributing to endothelial dysfunction and atherosclerosis. As a major source of
      vascular superoxide anion formation, an endothelial NAD(P)H oxidase, similar to
      the leukocyte enzyme, has been identified. METHODS AND RESULTS: To elucidate
      functional differences between NAD(P)H oxidases of endothelial cells and
      leukocytes, DNA sequences of endothelial NAD(P)H oxidase subunits were
      determined. Gp91phox cDNA sequence showed no difference between the 2 cell types.
      Endothelial p67phox cDNA sequence revealed 2 known polymorphisms, which do not
      affect NAD(P)H oxidase function. Next, we analyzed relative mRNA expression of
      NAD(P)H subunits in human umbilical vein endothelial cells (HUVECs) and
      leukocytes using a common cRNA standard in competitive reverse transcription
      polymerase chain reaction. NAD(P)H oxidase subunits p22phox and p47phox are
      expressed at a similar level in both cell types, whereas p67phox (2.5%) and
      gp91phox (1.1%) are expressed at a much lower level in endothelial cells than in
      leukocytes. Differences of gp91phox expression in leukocytes and HUVECs correlate
      with differences in superoxide release. Gp91phox mRNA and endothelial superoxide
      anion formation are induced in response to oxLDL in HUVECs. Furthermore, a lower
      gp91phox mRNA expression was found in internal mammary artery biopsy samples of
      patients with coronary artery disease treated with HMG-CoA reductase inhibitors
      before coronary bypass surgery. CONCLUSIONS: We conclude that oxLDL induces
      proatherosclerotic NAD(P)H oxidase expression and superoxide anion formation in
      human endothelial cells and an antioxidative potential of HMG-CoA reductase
      inhibition via reduction of vascular NAD(P)H oxidase expression.

PMID- 11591613
TI  - Effect of medroxyprogesterone acetate on endothelium-dependent vasodilation in
      postmenopausal women receiving estrogen.
AB  - BACKGROUND: Estrogen increases endothelium-dependent vasodilation in
      postmenopausal women. However, use of progestins in combination with estrogen may
      counter beneficial effects of estrogen on endothelium. We investigated the effect
      of medroxyprogesterone acetate (MPA) on estrogen-induced increase in endothelium
      dependent vasodilation in postmenopausal women. METHODS AND RESULTS:
      Postmenopausal women were treated daily with conjugated equine estrogen (CEE)
      0.625 mg (n=14), CEE 0.625 mg and MPA 2.5 mg (n=15) or CEE 0.625 mg and MPA 5.0
      mg (n=16) for 3 months. Plasma lipids and hormones were measured before and after
      treatment. Vasodilatory responses of the brachial artery were evaluated by
      measuring flow-mediated vasodilation (FMD) and nitroglycerin-induced vasodilation
      by use of high-resolution ultrasonography. Susceptibility of LDL to oxidation was
      analyzed by incubation with CuSO(4) while kinetics of conjugated diene formation
      was monitored. Plasma total and LDL cholesterol concentrations were decreased
      significantly in all groups. CEE increased FMD significantly, from 4.5+/-1.7% to
      8.5+/-2.8% (P<0.001). Addition of MPA reversed this effect in a concentration
      dependent manner (for MPA 2.5 mg, from 5.0+/-3.2% to 6.2+/-3.1%; for MPA 5.0 mg,
      from 4.9+/-3.4% to 3.6+/-3.7%; P=NS for each). No treatment significantly altered
      nitroglycerin-induced dilation. Lag time for conjugated diene formation was
      prolonged significantly in all groups, and the oxidation rate was significantly
      reduced. CONCLUSIONS: Concurrent MPA administration may offset favorable effects
      of estrogen on endothelial function in postmenopausal women. Because MPA did not
      diminish LDL-lowering and antioxidant effects of estrogen, MPA-induced inhibition
      of endothelium-dependent vasodilation may be independent of changes in oxidative
      susceptibility and plasma concentration of LDL.

PMID- 11591614
TI  - Real-time quantification and display of skin radiation during coronary
      angiography and intervention.
AB  - BACKGROUND: Radiographically guided investigations may be associated with
      excessive radiation exposure, which may cause skin injuries. The purpose of this
      study was to develop and test a system that measures in real time the dose
      applied to each 1-cm(2) area of skin, taking into account the movement of the x
      ray source and changes in the beam characteristics. The goal of such a system is
      to help prevent high doses that might cause skin injury. METHODS AND RESULTS: The
      entrance point, beam size, and dose at the skin of the patient were calculated by
      use of the geometrical settings of gantry, investigation table, and x-ray beam
      and an ionization chamber. The data are displayed graphically. Three hundred
      twenty-two sequential cardiac investigations in adult patients were analyzed. The
      mean peak entrance dose per investigation was 0.475 Gy to a mean skin area of 8.2
      cm(2). The cumulative KERMA-area product per investigation was 52.2 Gy/cm(2)
      (25.4 to 99.2 Gy/cm(2)), and the mean entrance beam size at the skin was 49.2
      cm(2). Twenty-eight percent of the patients (90/322) received a maximum dose of
      <1 Gy to a small skin area ( approximately 6 cm(2)), and 13.5% of the patients
      (42/322) received a maximum dose of >2 Gy. CONCLUSIONS: Monitoring of the dose
      distribution at the skin will alert the operator to the development of high-dose
      areas; by use of other gantry settings with nonoverlapping entrance fields,
      different generator settings, and extra collimation, skin lesion can be avoided.

PMID- 11591615
TI  - Parasympathetic neural activity accounts for the lowering of exercise heart rate
      at high altitude.
AB  - BACKGROUND: In chronic hypoxia, both heart rate (HR) and cardiac output (Q) are
      reduced during exercise. The role of parasympathetic neural activity in lowering
      HR is unresolved, and its influence on Q and oxygen transport at high altitude
      has never been studied. METHODS AND RESULTS: HR, Q, oxygen uptake, mean arterial
      pressure, and leg blood flow were determined at rest and during cycle exercise
      with and without vagal blockade with glycopyrrolate in 7 healthy lowlanders after
      9 weeks' residence at >/=5260 m (ALT). At ALT, glycopyrrolate increased resting
      HR by 80 bpm (73+/-4 to 153+/-4 bpm) compared with 53 bpm (61+/-3 to 114+/-6 bpm)
      at sea level (SL). During exercise at ALT, glycopyrrolate increased HR by
      approximately 40 bpm both at submaximal (127+/-4 to 170+/-3 bpm; 118 W) and
      maximal (141+/-6 to 180+/-2 bpm) exercise, whereas at SL, the increase was only
      by 16 bpm (137+/-6 to 153+/-4 bpm) at 118 W, with no effect at maximal exercise
      (181+/-2 bpm). Despite restoration of maximal HR to SL values, glycopyrrolate had
      no influence on Q, which was reduced at ALT. Breathing FIO(2)=0.55 at peak
      exercise restored Q and power output to SL values. CONCLUSIONS: Enhanced
      parasympathetic neural activity accounts for the lowering of HR during exercise
      at ALT without influencing Q. The abrupt restoration of peak exercise Q in
      chronic hypoxia to maximal SL values when arterial PO(2) and SO(2) are similarly
      increased suggests hypoxia-mediated attenuation of Q.

PMID- 11591616
TI  - Dysregulation of peripheral and central chemoreflex responses in Chagas' heart
      disease patients without heart failure.
AB  - BACKGROUND: The peripheral and central chemoreflexes are important autonomic
      mechanisms for regulating breathing and cardiovascular function. Although
      pathological inflammatory infiltration of the peripheral chemoreceptors and
      central nervous system has been reported in Chagas' disease, functional
      evaluation of chemoreflexes has not yet been performed. METHODS AND RESULTS: The
      hypothesis that chemoreflex function is altered in patients with Chagas' heart
      disease (CH) but normal left ventricle function was tested in 12 CH patients and
      13 matched control subjects. The ventilatory rate, minute ventilation, heart
      rate, mean arterial pressure, forearm blood flow, forearm vascular resistance,
      and venous norepi-nephrine responses to hypoxia and hypercapnia were determined.
      During hypoxia, the decrease in oxygen saturation was smaller in CH patients,
      despite a similar ventilatory response between groups. Both groups showed an
      increase in heart rate during hypoxia, but this response was blunted in CH
      patients. Although the mean arterial pressure response to hypoxia was similar in
      both groups, forearm vascular resistance significantly decreased in control
      subjects while remaining unchanged in CH patients. Moreover, a significant
      increase in plasma norepinephrine levels elicited by stimulation of peripheral
      chemoreceptors was observed only in the CH group. During hypercapnia, the
      increase in minute ventilation was smaller in CH patients, who did not exhibit
      the increase in norepinephrine observed in control subjects. CONCLUSIONS: These
      data suggest that CH potentiates respiratory, cardiovascular, and autonomic
      responses to peripheral chemoreceptor activation by hypoxia in patients with
      normal left ventricular function. The ventilatory and sympathetic responses to
      central chemoreceptor activation by hypercapnia, however, are significantly
      blunted.

PMID- 11591617
TI  - Hypothermia after cardiac arrest: feasibility and safety of an external cooling
      protocol.
AB  - BACKGROUND: No proven neuroprotective treatment exists for ischemic brain injury
      after cardiac arrest. Mild-to-moderate induced hypothermia (MIH) is effective in
      animal models. METHODS AND RESULTS: A safety and feasibility trial was designed
      to evaluate mild-to-moderate induced hypothermia by use of external cooling
      blankets after cardiac arrest. Inclusion criteria were return of spontaneous
      circulation within 60 minutes of advanced cardiac life support, hypothermia
      initiated within 90 minutes, persistent coma, and lack of acute myocardial
      infarction or unstable dysrhythmia. Hypothermia to 33 degrees C was maintained
      for 24 hours followed by passive rewarming. Nine patients were prospectively
      enrolled. Mean time from advanced cardiac life support to return of spontaneous
      circulation was 11 minutes (range 3 to 30); advanced cardiac life support to
      initiation of hypothermia was 78 minutes (range 40 to 109); achieving 33 degrees
      C took 301 minutes (range 90 to 690). Three patients completely recovered, and 1
      had partial neurological recovery. One patient developed unstable cardiac
      dysrhythmia. No other unexpected complications occurred. CONCLUSIONS: Mild-to
      moderate induced hypothermia after cardiac arrest is feasible and safe. However,
      external cooling is slow and imprecise. Efforts to speed the start of cooling and
      to improve the cooling process are needed.

PMID- 11591618
TI  - Vasoconstrictor effect of the angiotensin-converting enzyme-resistant, chymase
      specific substrate [Pro(11)(D)-Ala(12)] angiotensin I in human dorsal hand veins:
      in vivo demonstration of non-ace production of angiotensin II in humans.
AB  - BACKGROUND: [Pro(11)(D)-Ala(12)] angiotensin I is an ACE-resistant substrate
      specific for chymase. We used this peptide to determine whether a functionally
      significant non-ACE angiotensin (Ang) II-generating pathway exists in human
      dorsal hand veins. METHODS AND RESULTS: Using a modified Aellig technique, we
      studied the response to Ang I and [Pro(11)(D)-Ala(12)] Ang I in dorsal hand veins
      in vivo in patients with coronary heart disease. We measured the venoconstrictor
      effect of each peptide given before and after a 6.25-mg oral dose of the ACE
      inhibitor captopril or matching placebo. Placebo or captopril was given in a
      double-blind, randomized fashion. Ang I induced a mean+/-SEM venoconstrictor
      response of 45+/-11%, 40+/-10%, 55+/-8%, and 4+/-4% before placebo, after
      placebo, before captopril, and after captopril, respectively. Hence, the response
      to Ang I was reproducible and was reduced significantly only after treatment with
      captopril (P=0.002). [Pro(11)(D)-Ala(12)] Ang I induced a mean venoconstrictor
      response of 42+/-9%, 49+/-9%, 48+/-10%, and 54+/-11% before placebo, after
      placebo, before captopril, and after captopril, respectively. Hence, captopril
      had no significant effect on the response to [Pro(11)(D)-Ala(12)] Ang I.
      CONCLUSIONS: We have demonstrated that [Pro(11)(D)-Ala(12)] Ang I is able to
      induce venoconstriction in humans in vivo. With this specific pharmacological
      probe, we have shown that a non-ACE pathway capable of generating Ang II exists
      in human veins in vivo and is potentially functionally important. This pathway is
      likely to involve the enzyme chymase.

PMID- 11591619
TI  - Differential characteristics of neural circulatory control: early versus late
      after cardiac transplantation.
AB  - BACKGROUND: Reappearance of low-frequency (LF) (+/-0.10 Hz) oscillations in RR
      interval (RR) after cardiac transplantation is indicative of sympathetic efferent
      reinnervation. We hypothesized that restored LF oscillations in RR in heart
      transplant recipients (HTRs) are linked to oscillations in muscle sympathetic
      nerve traffic (MSNA). METHODS AND RESULTS: RR, RR variability, and MSNA were
      recorded 5+/-2 months (n=7, short-term HTRs) and 138+/-8 months (n=7, long-term
      HTRs) after heart transplantation and compared with matched hypertensive patients
      (n=7). A coherence function determined the coupling between LF oscillations in
      MSNA and RR. RR variance did not differ between short-term and long-term HTRs.
      However, LF variability was only 1+/-0.5 ms(2) in the short-term HTRs but was
      15+/-8 ms(2) in the long-term HTRs (P<0.05). Normalized LF variability was also
      higher in the long-term HTRs (40+/-14 normalized unites) versus the short-term
      HTRs (6+/-3 normalized united, P<0.05) but did not differ from the LF variability
      of the hypertensive patients. Long-term HTRs were taking less cyclosporine
      (P<0.01) but had higher MSNA than the short-term HTRs (62+/-7 versus 31+/-7
      burst/min, respectively, P<0.05). Coherence between LF oscillations in MSNA and
      RR was similar in the long-term HTRs (0.59+/-0.11) and the hypertensive patients
      (0.60+/-0.07) and was 3-fold greater than in the short-term HTRs (0.20+/-0.06,
      P<0.05). CONCLUSIONS: Cardiac reinnervation after long-term heart transplantation
      is characterized by a restoration of the coherence between LF oscillations in RR
      and MSNA. Higher MSNA in long-term than in short-term HTRs suggests that time
      elapsed after cardiac transplantation may be a major determinant of sympathetic
      excitation in heart transplant recipients.

PMID- 11591620
TI  - Mildly oxidized LDL induces activation of platelet-derived growth factor beta
      receptor pathway.
AB  - BACKGROUND: Mildly oxidized LDL (moxLDL) is thought to play a role in
      atherogenesis. MoxLDL induces derivatization of cell proteins and triggers a
      variety of intracellular signaling. We aimed to investigate whether moxLDL
      induced protein derivatization may influence the activity of platelet-derived
      growth factor receptor beta (PDGFRbeta), a tyrosine kinase receptor of major
      importance in vascular biology and atherogenesis. METHODS AND RESULTS: In
      cultured rabbit arterial smooth muscle cells, moxLDL induces activation of the
      PDGFRbeta signaling pathway, as shown by PDGFRbeta tyrosine phosphorylation on
      Western blot and coimmunoprecipitation of SH2-containing proteins. The cellular
      events involved in the moxLDL-induced PDGFRbeta activation can be summarized as
      follows. Oxidized lipids from moxLDL trigger two phases of PDGFRbeta activation
      involving two separate mechanisms, as shown by experiments on cultured cells (in
      situ) and on immunopurified PDGFRbeta (in vitro): (1) the first phase may be
      mediated by 4-hydroxynonenal, which induces PDGFRbeta adduct formation and
      subsequent PDGFRbeta activation (antioxidant-insensitive step); (2) the second
      phase involves ceramide-mediated generation of H(2)O(2) (these steps being
      inhibited by tosylphenylalanylchloromethylketone, an inhibitor of ceramide
      formation, and by antioxidant BHT, exogenous catalase, or overexpressed human
      catalase). Because 4-hydroxynonenal-PDGFRbeta adducts are also detected in
      atherosclerotic aortas, it is suggested that this novel mechanism of moxLDL
      induced PDGFRbeta activation may occur during atherogenesis. CONCLUSIONS: MoxLDL
      acts as a local autoparacrine mediator in the vascular wall, and PDGFRbeta acts
      as a sensor for both oxidized lipids and oxidative stress. This constitutes a
      novel mechanism of PDGFRbeta activation in atherosclerotic areas.

PMID- 11591622
TI  - Heme oxygenase-1 inhibits atherogenesis in Watanabe heritable hyperlipidemic
      rabbits.
AB  - BACKGROUND: Heme oxygenase-1 (HO-1) is proposed to have a variety of adaptive
      responses against oxidative stress. To examine the function of HO-1 against
      atherogenesis in vivo, we observed the effects of HO-1 inhibition on
      atherosclerotic lesion formation in Watanabe heritable hyperlipidemic rabbits
      (WHHL). Methods and Results- During 4 weeks of a 1% cholesterol diet, intravenous
      injections of Sn-protoporphyrin IX to inhibit HO-1 (S group, n=10) and saline as
      a control (C group, n=10) were given to 3-month-old WHHL rabbits. The percentages
      of en face atherosclerotic lesion areas in total descending aorta by Sudan IV
      staining (EFA) and the ratio of intima to media in microscopic atherosclerotic
      lesions in the ascending aortas (I/M) were calculated. Two different quantitative
      methods revealed significantly greater atherosclerotic lesions in the S group
      than the C group (EFA, P<0.001; I/M, P<0.005). HO-1 expression in atherosclerotic
      lesions was confirmed by Northern blot and immunohistochemical analyses. The
      dominant cell types expressing HO-1 were macrophages and foam cells, in which
      oxidized phospholipids were also accumulated. HO inhibition increased plasma and
      tissue lipid peroxide levels without affecting plasma lipid co osition.
      CONCLUSIONS: These results suggest the possibilities that HO-1 has
      antiatherogenic properties in vivo and that the antiatherogenic properties of HO
      1 are conducted through the prevention of lipid peroxidation.

PMID- 11591621
TI  - Regulation of endothelial nitric oxide synthase expression in the vascular wall
      and in mononuclear cells from hypercholesterolemic rabbits.
AB  - BACKGROUND: We recently obtained evidence demonstrating that cultured bovine
      endothelial cells contain cytosolic proteins that form complexes with the 3'
      untranslated region of endothelial nitric oxide synthase (eNOS) mRNA and are
      associated with its destabilization. The aim of this study was to determine the
      presence of such proteins and eNOS expression in hypercholesterolemic rabbits as
      an in vivo model of endothelial dysfunction. METHODS AND RESULTS: Endothelium
      dependent relaxation to acetylcholine and the calcium ionophore A23187 was
      reduced in aortic segments from hypercholesterolemic rabbits compared with
      controls. Treatment of hypercholesterolemic rabbits with cerivastatin (0.1 mg. kg
      body wt(-1). d(-1)) restored endothelium-dependent relaxation. Aortic eNOS
      expression was reduced in hypercholesterolemic rabbits and was accompanied by
      enhanced binding activity of a 60-kDa cytosolic protein and reduced stability of
      eNOS mRNA. Cerivastatin treatment upregulated eNOS expression and reduced the
      interaction of the cytosolic protein with the 3'-untranslated region of eNOS
      mRNA. Mononuclear cells from hypercholesterolemic rabbits also showed a marked
      reduction of eNOS expression and eNOS mRNA stability and an increase in binding
      activity of the cytosolic protein, which were also prevented by cerivastatin
      treatment. CONCLUSIONS: These results demonstrate the presence of a 60-kDa
      protein that binds to eNOS mRNA and reductions in eNOS expression in both
      vascular wall and mononuclear cells that are prevented by cerivastatin.

PMID- 11591623
TI  - Single oral dose of geranylgeranylacetone induces heat-shock protein 72 and
      renders protection against ischemia/reperfusion injury in rat heart.
AB  - BACKGROUND: Induction of heat-shock proteins (HSPs) results in cardioprotection
      against ischemic insult. Geranylgeranylacetone (GGA), known as an antiulcer
      agent, reportedly induces HSP72 in the gastric mucosa and small intestine of
      rats. The present study tested the hypothesis that oral GGA would induce HSP72 in
      the heart and thus render cardioprotection against ischemia/reperfusion injury in
      rats. METHODS AND RESULTS: Cardiac expression of HSPs was quantitatively
      evaluated in rats by Western blot analysis. Ten minutes of whole-body
      hyperthermia induced HSP72 expression in the rat hearts. A single oral dose of
      GGA (200 mg/kg) also induced expression of HSP72, which peaked at 24 hours after
      administration. Therefore, isolated perfused heart experiments using a
      Langendorff apparatus were performed 24 hours after administration of 200 mg/kg
      GGA (GGA group) or vehicle (control group). After a 5-minute stabilization
      period, no-flow global ischemia was given for 20, 40, or 60 minutes, followed by
      30 minutes of reperfusion. During reperfusion, the functional recovery was
      greater and the released creatine kinase was less in the GGA group than in the
      control group. Electron microscopy findings revealed that the
      ischemia/reperfusion-induced damage of myocardial cells was prevented in GGA
      treated myocytes. CONCLUSIONS: The results suggest that oral GGA is
      cardioprotective against ischemic insult through its induction of HSP72.

PMID- 11591624
TI  - Chronic phosphocreatine depletion by the creatine analogue beta
      guanidinopropionate is associated with increased mortality and loss of ATP in
      rats after myocardial infarction.
AB  - BACKGROUND: The failing myocardium is characterized by reductions of
      phosphocreatine (PCr) and free creatine content and by decreases of energy
      reserve via creatine kinase (CK), ie, CK reaction velocity (Flux(CK)). It has
      remained unclear whether these changes contribute directly to contractile
      dysfunction. In the present study, myocardial PCr stores in a heart failure model
      were further depleted by feeding of the PCr analogue beta-guanidinopropionate
      (GP). Functional and metabolic consequences were studied. METHODS AND RESULTS:
      Rats were subjected to sham operation or left coronary artery ligation (MI).
      Surviving rats were assigned to 4 groups and fed with 0% (n=7, Sham; n=5, MI) or
      1% (n=7 Sham+GP, n=8 MI+GP) GP. Two additional groups were fed GP for 2 or 4
      weeks before MI. After 8 weeks, hearts were isolated and perfused, and left
      ventricular pressure-volume curves were obtained. High-energy phosphate
      metabolism was determined with (31)P NMR spectroscopy. After GP feeding or MI,
      left ventricular pressure-volume curves were depressed by 33% and 32%,
      respectively, but GP feeding in MI hearts did not further impair mechanical
      function. Both MI and GP feeding reduced PCr content and Flux(CK), but here,
      effects were additive. In MI+GP rats, PCr levels and Flux(CK) were reduced by 87%
      and 94%, respectively. Although ATP levels were maintained in the GP and MI
      groups, ATP content was reduced by 18% in MI+GP hearts. Furthermore, 24-hour
      mortality in GP-prefed rats was 100%. CONCLUSIONS: Rats with an 87% predepletion
      of myocardial PCr content cannot survive an acute MI. Chronically infarcted
      hearts subjected to additional PCr depletion cannot maintain ATP homeostasis.

PMID- 11591625
TI  - Effect of short pulsed nonablative infrared laser irradiation on vascular cells
      in vitro and neointimal hyperplasia in a rabbit balloon injury model.
AB  - BACKGROUND: Neointimal hyperplasia after PTCA is an important component of
      restenosis. METHODS AND RESULTS: Cultures of rabbit endothelial cells and smooth
      muscle cells (SMCs) were irradiated with different doses of nonablative infrared
      (1064-nm) radiation. Normalized viability index detected with nondestructive
      Alamar Blue assay and direct cell count were studied. Our experiments
      demonstrated dose-dependent cytostatic or cytotoxic effects of laser irradiation.
      We also evaluated the long-term effect of endoluminal nonablative infrared laser
      irradiation on neointimal hyperplasia in a rabbit balloon injury model. PTCA of
      both iliac arteries of 23 New Zealand White rabbits was performed. One iliac
      artery was subjected to intra-arterial subablative infrared irradiation via a
      diffuse tip fiber. The contralateral vessel served as control. The diet was
      supplemented with 0.25% cholesterol and 2% peanut oil for 10 days before and 60
      days after PTCA. Morphometry after 60 days showed that intimal areas were 0.76+/
      0.18 and 1.85+/-0.30 mm(2) in the laser and control arteries, respectively
      (P=2.2x10(-11)). CONCLUSIONS: We conclude that nonablative infrared laser
      inhibited neointimal hyperplasia after PTCA in cholesterol-fed rabbits for up to
      60 days.

PMID- 11591627
TI  - Improving coronary heart disease risk assessment in asymptomatic people: role of
      traditional risk factors and noninvasive cardiovascular tests.

PMID- 11591626
TI  - Vasopeptidase inhibitors: a new therapeutic concept in cardiovascular disease?
AB  - The cardiovascular system is regulated by hemodynamic and neurohumoral
      mechanisms. These regulatory systems play a key role in modulating cardiac
      function, vascular tone, and structure. Although neurohumoral systems are
      essential in vascular homeostasis, they become maladaptive in disease states such
      as hypertension, coronary disease, and heart failure. The clinical success of ACE
      inhibitors has led to efforts to block other humoral systems. Neutral
      endopeptidase (NEP) is an endothelial cell surface zinc metallopeptidase with
      similar structure and catalytic site. NEP is the major enzymatic pathway for
      degradation of natriuretic peptides, a secondary enzymatic pathway for
      degradation of kinins, and adrenomedullin. The natriuretic peptides can be viewed
      as endogenous inhibitors of the renin angiotensin system. Inhibition of NEP
      increases levels of atrial natriuretic peptide (ANP), brain natriuretic peptide
      (BNP) of myocardial cell origin, and C-type natriuretic peptide (CNP) of
      endothelial cell origin as well as bradykinin and adrenomedullin. By
      simultaneously inhibiting the renin-angiotensin-aldosterone system and
      potentiating the natriuretic peptide and kinin systems, vasopeptidase inhibitors
      reduce vasoconstriction, enhance vasodilation, improve sodium/water balance, and,
      in turn, decrease peripheral vascular resistance and blood pressure and improve
      local blood flow. Within the blood vessel wall, this leads to a reduction of
      vasoconstrictor and proliferative mediators such as angiotensin II and increased
      local levels of bradykinin (and, in turn, nitric oxide) and natriuretic peptides.
      Preliminary clinical experiences with vasopeptidase inhibitors are encouraging.
      Thus, the combined inhibition of ACE and neutral endopeptidase is a new and
      promising approach to treat patients with hypertension, atherosclerosis, or heart
      failure.

PMID- 11591628
TI  - Microvascular obstruction after nonsurgical septal reduction for the treatment of
      hypertrophic cardiomyopathy.

PMID- 11591629
TI  - Dietary protein and weight reduction: a statement for healthcare professionals
      from the Nutrition Committee of the Council on Nutrition, Physical Activity, and
      Metabolism of the American Heart Association.
AB  - High-protein diets have recently been proposed as a "new" strategy for successful
      weight loss. However, variations of these diets have been popular since the
      1960s. High-protein diets typically offer wide latitude in protein food choices,
      are restrictive in other food choices (mainly carbohydrates), and provide
      structured eating plans. They also often promote misconceptions about
      carbohydrates, insulin resistance, ketosis, and fat burning as mechanisms of
      action for weight loss. Although these diets may not be harmful for most healthy
      people for a short period of time, there are no long-term scientific studies to
      support their overall efficacy and safety. These diets are generally associated
      with higher intakes of total fat, saturated fat, and cholesterol because the
      protein is provided mainly by animal sources. In high-protein diets, weight loss
      is initially high due to fluid loss related to reduced carbohydrate intake,
      overall caloric restriction, and ketosis-induced appetite suppression. Beneficial
      effects on blood lipids and insulin resistance are due to the weight loss, not to
      the change in caloric composition. Promoters of high-protein diets promise
      successful results by encouraging high-protein food choices that are usually
      restricted in other diets, thus providing initial palatability, an attractive
      alternative to other weight-reduction diets that have not worked for a variety of
      reasons for most individuals. High-protein diets are not recommended because they
      restrict healthful foods that provide essential nutrients and do not provide the
      variety of foods needed to adequately meet nutritional needs. Individuals who
      follow these diets are therefore at risk for compromised vitamin and mineral
      intake, as well as potential cardiac, renal, bone, and liver abnormalities
      overall.

PMID- 11591630
TI  - Fluoroscopic diagnosis of native valve endocarditis.

PMID- 11591631
TI  - T-wave shape in clinical research.

PMID- 11591632
TI  - Sex differences in the prognosis of congestive heart failure.

PMID- 11591633
TI  - Angiotensin II type 1 receptor blockers and congestive heart failure.

PMID- 11591634
TI  - Optimal activated clotting time during percutaneous coronary intervention.

PMID- 11591635
TI  - Third abiocor artificial heart implanted in Houston.

PMID- 11591636
TI  - Sharing duties in the family.

PMID- 11591637
TI  - Evolutionarily conserved noncoding DNA in the human genome: how much and what
      for?

PMID- 11591638
TI  - A clone-array pooled shotgun strategy for sequencing large genomes.
AB  - A simplified strategy for sequencing large genomes is proposed. Clone-Array
      Pooled Shotgun Sequencing (CAPSS) is based on pooling rows and columns of arrayed
      genomic clones, for shotgun library construction. Random sequences are
      accumulated, and the data are processed by sequential comparison of rows and
      columns to assemble the sequence of clones at points of intersection. Compared
      with either a clone-by-clone approach or whole-genome shotgun sequencing, CAPSS
      requires relatively few library constructions and only minimal computational
      power for a complete genome assembly. The strategy is suitable for sequencing
      large genomes for which there are no sequence-ready maps, but for which
      relatively high resolution STS maps and highly redundant BAC libraries are
      available. It is immediately applicable to the sequencing of mouse, rat,
      zebrafish, and other important genomes, and can be managed in a cooperative
      fashion to take advantage of a distributed international DNA sequencing capacity.

PMID- 11591639
TI  - Partitioning of tissue expression accompanies multiple duplications of the Na+/K+
      ATPase alpha subunit gene.
AB  - Vertebrate genomes contain multiple copies of related genes that arose through
      gene duplication. In the past it has been proposed that these duplicated genes
      were retained because of acquisition of novel beneficial functions. A more recent
      model, the duplication-degeneration-complementation hypothesis (DDC), posits that
      the functions of a single gene may become separately allocated among the
      duplicated genes, rendering both duplicates essential. Thus far, empirical
      evidence for this model has been limited to the engrailed and sox family of
      developmental regulators, and it has been unclear whether it may also apply to
      ubiquitously expressed genes with essential functions for cell survival. Here we
      describe the cloning of three zebrafish alpha subunits of the Na(+),K(+)-ATPase
      and a comprehensive evolutionary analysis of this gene family. The predicted
      amino acid sequences are extremely well conserved among vertebrates. The
      evolutionary relationships and the map positions of these genes and of other
      alpha-like sequences indicate that both tandem and ploidy duplications
      contributed to the expansion of this gene family in the teleost lineage. The
      duplications are accompanied by acquisition of clear functional specialization,
      consistent with the DDC model of genome evolution.

PMID- 11591640
TI  - Annotation transfer for genomics: measuring functional divergence in multi-domain
      proteins.
AB  - Annotation transfer is a principal process in genome annotation. It involves
      "transferring" structural and functional annotation to uncharacterized open
      reading frames (ORFs) in a newly completed genome from experimentally
      characterized proteins similar in sequence. To prevent errors in genome
      annotation, it is important that this process be robust and statistically well
      characterized, especially with regard to how it depends on the degree of sequence
      similarity. Previously, we and others have analyzed annotation transfer in single
      domain proteins. Multi-domain proteins, which make up the bulk of the ORFs in
      eukaryotic genomes, present more complex issues in functional conservation. Here
      we present a large-scale survey of annotation transfer in these proteins, using
      scop superfamilies to define domain folds and a thesaurus based on SWISS-PROT
      keywords to define functional categories. Our survey reveals that multi-domain
      proteins have significantly less functional conservation than single-domain ones,
      except when they share the exact same combination of domain folds. In particular,
      we find that for multi-domain proteins, approximate function can be accurately
      transferred with only 35% certainty for pairs of proteins sharing one structural
      superfamily. In contrast, this value is 67% for pairs of single-domain proteins
      sharing the same structural superfamily. On the other hand, if two multi-domain
      proteins contain the same combination of two structural superfamilies the
      probability of their sharing the same function increases to 80% in the case of
      complete coverage along the full length of both proteins, this value increases
      further to > 90%. Moreover, we found that only 70 of the current total of 455
      structural superfamilies are found in both single and multi-domain proteins and
      only 14 of these were associated with the same function in both categories of
      proteins. We also investigated the degree to which function could be transferred
      between pairs of multi-domain proteins with respect to the degree of sequence
      similarity between them, finding that functional divergence at a given amount of
      sequence similarity is always about two-fold greater for pairs of multi-domain
      proteins (sharing similarity over a single domain) in comparison to pairs of
      single-domain ones, though the overall shape of the relationship is quite
      similar. Further information is available at http://partslist.org/func or
      http://bioinfo.mbb.yale.edu/partslist/func.

PMID- 11591641
TI  - Understanding the adaptation of Halobacterium species NRC-1 to its extreme
      environment through computational analysis of its genome sequence.
AB  - The genome of the halophilic archaeon Halobacterium sp. NRC-1 and predicted
      proteome have been analyzed by computational methods and reveal characteristics
      relevant to life in an extreme environment distinguished by hypersalinity and
      high solar radiation: (1) The proteome is highly acidic, with a median pI of 4.9
      and mostly lacking basic proteins. This characteristic correlates with high
      surface negative charge, determined through homology modeling, as the major
      adaptive mechanism of halophilic proteins to function in nearly saturating
      salinity. (2) Codon usage displays the expected GC bias in the wobble position
      and is consistent with a highly acidic proteome. (3) Distinct genomic domains of
      NRC-1 with bacterial character are apparent by whole proteome BLAST analysis,
      including two gene clusters coding for a bacterial-type aerobic respiratory
      chain. This result indicates that the capacity of halophiles for aerobic
      respiration may have been acquired through lateral gene transfer. (4) Two regions
      of the large chromosome were found with relatively lower GC composition and
      overrepresentation of IS elements, similar to the minichromosomes. These IS
      element-rich regions of the genome may serve to exchange DNA between the three
      replicons and promote genome evolution. (5) GC-skew analysis showed evidence for
      the existence of two replication origins in the large chromosome. This finding
      and the occurrence of multiple chromosomes indicate a dynamic genome organization
      with eukaryotic character.

PMID- 11591642
TI  - Evolutionarily conserved sequences on human chromosome 21.
AB  - Comparison of human sequences with the DNA of other mammals is an excellent means
      of identifying functional elements in the human genome. Here we describe the
      utility of high-density oligonucleotide arrays as a rapid approach for comparing
      human sequences with the DNA of multiple species whose sequences are not
      presently available. High-density arrays representing approximately 22.5 Mb of
      nonrepetitive human chromosome 21 sequence were synthesized and then hybridized
      with mouse and dog DNA to identify sequences conserved between humans and mice
      (human-mouse elements) and between humans and dogs (human-dog elements). Our data
      show that sequence comparison of multiple species provides a powerful empiric
      method for identifying actively conserved elements in the human genome. A large
      fraction of these evolutionarily conserved elements are present in regions on
      chromosome 21 that do not encode known genes.

PMID- 11591643
TI  - Abundance, distribution, and transcriptional activity of repetitive elements in
      the maize genome.
AB  - Long terminal repeat (LTR) retrotransposons have been shown to make up much of
      the maize genome. Although these elements are known to be prevalent in plant
      genomes of a middle-to-large size, little information is available on the
      relative proportions composed by specific families of elements in a single
      genome. We sequenced a library of randomly sheared genomic DNA from maize to
      characterize this genome. BLAST analysis of these sequences demonstrated that the
      maize genome is composed of diverse sequences that represent numerous families of
      retrotransposons. The largest families contain the previously described elements
      Huck, Ji, and Opie. Approximately 5% of the sequences are predicted to encode
      proteins. The genomic abundance of 16 families of elements was estimated by
      hybridization to an array of 10,752 maize bacterial artificial chromosome (BAC)
      clones. Comparisons of the number of elements present on individual BACs
      indicated that retrotransposons are in general randomly distributed across the
      maize genome. A second library was constructed that was selected to contain
      sequences hypomethylated in the maize genome. Sequence analysis of this library
      indicated that retroelements abundant in the genome are poorly represented in
      hypomethylated regions. Fifty-six retroelement sequences corresponding to the
      integrase and reverse transcriptase domains were isolated from approximately
      407,000 maize expressed sequence tags (ESTs). Phylogenetic analysis of these and
      the genomic retroelement sequences indicated that elements most abundant in the
      genome are less abundant at the transcript level than are more rare
      retrotransposons. Additional phylogenies also demonstrated that rice and maize
      retrotransposon families are frequently more closely related to each other than
      to families within the same species. An analysis of the GC content of the maize
      genomic library and that of maize ESTs did not support recently published data
      that the gene space in maize is found within a narrow GC range, but does indicate
      that genic sequences have a higher GC content than intergenic sequences (52% vs.
      47% GC).

PMID- 11591644
TI  - A novel active L1 retrotransposon subfamily in the mouse.
AB  - Unlike human L1 retrotransposons, the 5' UTR of mouse L1 elements contains tandem
      repeats of approximately 200 bp in length called monomers. Multiple L1
      subfamilies exist in the mouse which are distinguished by their monomer
      sequences. We previously described a young subfamily, called the T(F) subfamily,
      which contains approximately 1800 active elements among its 3000 full-length
      members. Here we characterize a novel subfamily of mouse L1 elements, G(F), which
      has unique monomer sequence and unusual patterns of monomer organization. A
      majority of these G(F) elements also have a unique length polymorphism in ORF1.
      Polymorphism analysis of G(F) elements in various mouse subspecies and laboratory
      strains revealed that, like T(F), the G(F) subfamily is young and expanding.
      About 1500 full-length G(F) elements exist in the diploid mouse genome and, based
      on the results of a cell culture assay, approximately 400 G(F) elements are
      potentially capable of retrotransposition. We also tested 14 A-type subfamily
      elements in the assay and estimate that about 900 active A elements may be
      present in the mouse genome. Thus, it is now known that there are three large
      active subfamilies of mouse L1s; T(F), A, and G(F), and that in total
      approximately 3000 full-length elements are potentially capable of active
      retrotransposition. This number is in great excess to the number of L1 elements
      thought to be active in the human genome.

PMID- 11591645
TI  - A comparative molecular analysis of developing mouse forelimbs and hindlimbs
      using serial analysis of gene expression (SAGE).
AB  - The analysis of differentially expressed genes is a powerful approach to
      elucidate the genetic mechanisms underlying the morphological and evolutionary
      diversity among serially homologous structures, both within the same organism
      (e.g., hand vs. foot) and between different species (e.g., hand vs. wing). In the
      developing embryo, limb-specific expression of Pitx1, Tbx4, and Tbx5 regulates
      the determination of limb identity. However, numerous lines of evidence,
      including the fact that these three genes encode transcription factors, indicate
      that additional genes are involved in the Pitx1-Tbx hierarchy. To examine the
      molecular distinctions coded for by these factors, and to identify novel genes
      involved in the determination of limb identity, we have used Serial Analysis of
      Gene Expression (SAGE) to generate comprehensive gene expression profiles from
      intact, developing mouse forelimbs and hindlimbs. To minimize the extraction of
      erroneous SAGE tags from low-quality sequence data, we used a new algorithm to
      extract tags from -analyzed sequence data and obtained 68,406 and 68,450 SAGE
      tags from forelimb and hindlimb SAGE libraries, respectively. We also developed
      an improved method for determining the identity of SAGE tags that increases the
      specificity of and provides additional information about the confidence of the
      tag-UniGene cluster match. The most differentially expressed gene between our
      SAGE libraries was Pitx1. The differential expression of Tbx4, Tbx5, and several
      limb-specific Hox genes was also detected; however, their abundances in the SAGE
      libraries were low. Because numerous other tags were differentially expressed at
      this low level, we performed a 'virtual' subtraction with 362,344 tags from six
      additional nonlimb SAGE libraries to further refine this set of candidate genes.
      This subtraction reduced the number of candidate genes by 74%, yet preserved the
      previously identified regulators of limb identity. This study presents the gene
      expression complexity of the developing limb and identifies candidate genes
      involved in the regulation of limb identity. We propose that our computational
      tools and the overall strategy used here are broadly applicable to other SAGE
      based studies in a variety of organisms. [SAGE data are all available at GEO
      (http://www.ncbi.nlm.nih.gov/geo/) under accession nos. GSM55 and GSM56, which
      correspond to the forelimb and hindlimb raw SAGE data.]

PMID- 11591646
TI  - Partial deletion of the bovine ED1 gene causes anhidrotic ectodermal dysplasia in
      cattle.
AB  - Anhidrotic ectodermal dysplasia (ED1) is characterized by hypotrichosis, reduced
      number of sweat glands, and incisior anodontia in human, mouse, and cattle. In
      affected humans and mice, mutations in the ED1 gene coding for ectodysplasin 1
      are found. Ectodysplasin 1 is a novel trimeric transmembrane protein with an
      extracellular TNF-like signaling domain that is believed to be involved in the
      formation of hair follicles and tooth buds during fetal development. We report
      the construction of a 480-kb BAC contig harboring the complete bovine ED1 gene on
      BTA Xq22-Xq24. Physical mapping and sequence analysis of the coding parts of the
      ED1 gene revealed that a large genomic region including exon 3 of the ED1 gene is
      deleted in cattle with anhidrotic ectodermal dysplasia in a family of German
      Holstein cattle with three affected maternal half sibs.

PMID- 11591647
TI  - Whole genome comparison of Campylobacter jejuni human isolates using a low-cost
      microarray reveals extensive genetic diversity.
AB  - Campylobacter jejuni is the leading cause of bacterial food-borne diarrhoeal
      disease throughout the world, and yet is still a poorly understood pathogen.
      Whole genome microarray comparisons of 11 C. jejuni strains of diverse origin
      identified genes in up to 30 NCTC 11168 loci ranging from 0.7 to 18.7 kb that are
      either absent or highly divergent in these isolates. Many of these regions are
      associated with the biosynthesis of surface structures including flagella, lipo
      oligosaccharide, and the newly identified capsule. Other strain-variable genes of
      known function include those responsible for iron acquisition, DNA
      restriction/modification, and sialylation. In fact, at least 21% of genes in the
      sequenced strain appear dispensable as they are absent or highly divergent in one
      or more of the isolates tested, thus defining 1300 C. jejuni core genes. Such
      core genes contribute mainly to metabolic, biosynthetic, cellular, and regulatory
      processes, but many virulence determinants are also conserved. Comparison of the
      capsule biosynthesis locus revealed conservation of all the genes in this region
      in strains with the same Penner serotype as strain NCTC 11168. By contrast,
      between 5 and 17 NCTC 11168 genes in this region are either absent or highly
      divergent in strains of a different serotype from the sequenced strain, providing
      further evidence that the capsule accounts for Penner serotype specificity. These
      studies reveal extensive genetic diversity among C. jejuni strains and pave the
      way toward identifying correlates of pathogenicity and developing improved
      epidemiological tools for this problematic pathogen.

PMID- 11591648
TI  - Bayesian analysis of haplotypes for linkage disequilibrium mapping.
AB  - Haplotype analysis of disease chromosomes can help identify probable historical
      recombination events and localize disease mutations. Most available analyses use
      only marginal and pairwise allele frequency information. We have developed a
      Bayesian framework that utilizes full haplotype information to overcome various
      complications such as multiple founders, unphased chromosomes, data
      contamination, and incomplete marker data. A stochastic model is used to describe
      the dependence structure among several variables characterizing the observed
      haplotypes, for example, the ancestral haplotypes and their ages, mutation rate,
      recombination events, and the location of the disease mutation. An efficient
      Markov chain Monte Carlo algorithm was developed for computing the estimates of
      the quantities of interest. The method is shown to perform well in both real data
      sets (cystic fibrosis data and Friedreich ataxia data) and simulated data sets.
      The program that implements the proposed method, BLADE, as well as the two real
      datasets, can be obtained from
      http://www.fas.harvard.edu/~junliu/TechRept/01folder/diseq_prog.tar.gz.

PMID- 11591649
TI  - SSAHA: a fast search method for large DNA databases.
AB  - We describe an algorithm, SSAHA (Sequence Search and Alignment by Hashing
      Algorithm), for performing fast searches on databases containing multiple
      gigabases of DNA. Sequences in the database are preprocessed by breaking them
      into consecutive k-tuples of k contiguous bases and then using a hash table to
      store the position of each occurrence of each k-tuple. Searching for a query
      sequence in the database is done by obtaining from the hash table the "hits" for
      each k-tuple in the query sequence and then performing a sort on the results. We
      discuss the effect of the tuple length k on the search speed, memory usage, and
      sensitivity of the algorithm and present the results of computational experiments
      which show that SSAHA can be three to four orders of magnitude faster than BLAST
      or FASTA, while requiring less memory than suffix tree methods. The SSAHA
      algorithm is used for high-throughput single nucleotide polymorphism (SNP)
      detection and very large scale sequence assembly. Also, it provides Web-based
      sequence search facilities for Ensembl projects.

PMID- 11591650
TI  - A human cDNA expression library in yeast enriched for open reading frames.
AB  - We developed a high-throughput technique for the generation of cDNA libraries in
      the yeast Saccharomyces cerevisiae which enables the selection of cloned cDNA
      inserts containing open reading frames (ORFs). For direct screening of random
      primed cDNA libraries, we have constructed a yeast shuttle/expression vector, the
      so-called ORF vector pYEXTSH3, which allows the enriched growth of protein
      expression clones. The selection system is based on the HIS3 marker gene fused to
      the C terminus of the cDNA insert. The cDNAs cloned in-frame result in histidine
      prototrophic yeast cells growing on minimal medium, whereas clones bearing the
      vector without insert or out-of-frame inserts should not grow on this medium. A
      randomly primed cDNA library from human fetal brain tissue was cloned in this
      novel vector, and using robot technology the selected clones were arrayed in
      microtiter plates and were analyzed by sequencing and for protein expression. In
      the constructed cDNA expression library, about 60% of clones bear an insert in
      the correct reading frame. In comparison to unselected libraries it was possible
      to increase the clones with inserts in the correct reading frame more than
      fourfold, from 14% to 60%. With the expression system described here, we could
      avoid time-consuming and costly techniques for identification of clones
      expressing protein by using antibody screening on high-density filters and
      subsequently rearraying the selected clones in a new "daughter" library. The
      advantage of this ORF vector is that, in a one-step screening procedure, it
      allows the generation of expression libraries enriched for clones with correct
      reading frames as sources of recombinant proteins.

PMID- 11591651
TI  - Mouse BAC ends quality assessment and sequence analyses.
AB  - A large-scale BAC end-sequencing project at The Institute for Genomic Research
      (TIGR) has generated one of the most extensive sets of sequence markers for the
      mouse genome to date. With a sequencing success rate of >80%, an average read
      length of 485 bp, and ABI3700 capillary sequencers, we have generated 449,234
      nonredundant mouse BAC end sequences (mBESs) with 218 Mb total from 257,318
      clones from libraries RPCI-23 and RPCI-24, representing 15x clone coverage, 7%
      sequence coverage, and a marker every 7 kb across the genome. A total of 191,916
      BACs have sequences from both ends providing 12x genome coverage. The average Q20
      length is 406 bp and 84% of the bases have phred quality scores > or = 20. RPCI
      24 mBESs have more Q20 bases and longer reads on average than RPCI-23 sequences.
      ABI3700 sequencers and the sample tracking system ensure that > 95% of mBESs are
      associated with the right clone identifiers. We have found that a significant
      fraction of mBESs contains L1 repeats and approximately 48% of the clones have
      both ends with > or = 100 bp contiguous unique Q20 bases. About 3% mBESs match
      ESTs and > 70% of matches were conserved between the mouse and the human or the
      rat. Approximately 0.1% mBESs contain STSs. About 0.2% mBESs match human finished
      sequences and > 70% of these sequences have EST hits. The analyses indicate that
      our high-quality mouse BAC end sequences will be a valuable resource to the
      community.

PMID- 11591652
TI  - High-resolution BAC-based map of the central portion of mouse chromosome 5.
AB  - The current strategy for sequencing the mouse genome involves the combination of
      a whole-genome shotgun approach with clone-based sequencing. High-resolution
      physical maps will provide a foundation for assembling contiguous segments of
      sequence. We have established a bacterial artificial chromosome (BAC)-based map
      of a 5-Mb region on mouse Chromosome 5, encompassing three gene families:
      receptor tyrosine kinases (PdgfraKit-Kdr), nonreceptor protein-tyrosine type
      kinases (Tec-Txk), and type-A receptors for the neurotransmitter GABA (Gabra2,
      Gabrb1, Gabrg1, and Gabra4). The construction of a BAC contig was initiated by
      hybridization screening the C57BL/6J (RPCI-23) BAC library, using known genes and
      sequence tagged sites (STSs). Additional overlapping clones were identified by
      searching the database of available restriction fingerprints for the RPCI-23 and
      RPCI-24 libraries. This effort resulted in the selection of >600 BAC clones, 251
      kb of BAC-end sequences, and the placement of 40 known and/or predicted genes
      within this 5-Mb region. We use this high-resolution map to illustrate the
      integration of the BAC fingerprint map with a radiation-hybrid map via assembled
      expressed sequence tags (ESTs). From annotation of three representative BAC
      clones we demonstrate that up to 98% of the draft sequence for each contig could
      be ordered and oriented using known genes, BAC ends, consensus sequences for
      transcript assemblies, and comparisons with orthologous human sequence. For
      functional studies, annotation of sequence fragments as they are assembled into
      50-200-kb stretches will be remarkably valuable.

PMID- 11591653
TI  - Protein-protein interaction panel using mouse full-length cDNAs.
AB  - We have developed a novel assay system for systematic analysis of protein-protein
      interactions (PPIs) that is characteristic of a PCR-mediated rapid sample
      preparation and a high-throughput assay system based on the mammalian two-hybrid
      method. Using gene-specific primers, we successfully constructed the assay
      samples by two rounds of PCR with up to 3.6 kb from the first-round PCR
      fragments. In the assay system, we designed all the steps to be performed by
      adding only samples, reagents, and cells into 384-well assay plates using two
      types of semiautomatic multiple dispensers. The system enabled us examine more
      than 20,000 assay wells per day. We detected 145 interactions in our pilot study
      using 3500 samples derived from mouse full-length enriched cDNAs. Analysis of the
      interaction data showed both several significant interaction clusters and
      predicted functions of a few uncharacterized proteins. In combination with our
      comprehensive mouse full-length cDNA clone bank covering a large part of the
      whole genes, our high-throughput assay system will discover many interactions to
      facilitate understanding of the function of uncharacterized proteins and the
      molecular mechanism of crucial biological processes, and also enable completion
      of a rough draft of the entire PPI panel in certain cell types or tissues of
      mouse within a short time.

PMID- 11591654
TI  - DIAN: a novel algorithm for genome ontological classification.
AB  - Faced with the determination of many completely sequenced genomes, computational
      biology is now faced with the challenge of interpreting the significance of these
      data sets. A multiplicity of data-related problems impedes this goal: Biological
      annotations associated with raw data are often not normalized, and the data
      themselves are often poorly interrelated and their interpretation unclear. All of
      these problems make interpretation of genomic databases increasingly difficult.
      With the current explosion of sequences now available from the human genome as
      well as from model organisms, the importance of sorting this vast amount of
      conceptually unstructured source data into a limited universe of genes, proteins,
      functions, structures, and pathways has become a bottleneck for the field. To
      address this problem, we have developed a method of interrelating data sources by
      applying a novel method of associating biological objects to ontologies. We have
      developed an intelligent knowledge-based algorithm, to support biological
      knowledge mapping, and, in particular, to facilitate the interpretation of
      genomic data. In this respect, the method makes it possible to inventory genomes
      by collapsing multiple types of annotations and normalizing them to various
      ontologies. By relying on a conceptual view of the genome, researchers can now
      easily navigate the human genome in a biologically intuitive, scientifically
      accurate manner.

PMID- 11591655
TI  - Ceramic capillaries for use in microarray fabrication.
AB  - We have used ceramic capillary tips generally used in the microelectronics
      industry for the production of DNA microarrays. The ceramic tips improve the
      morphology of microarray elements, allow higher element density, and increase
      printing tip life over the customary slotted stainless-steel pins. Ceramic tips
      are less expensive than steel pins and allow printing from 1536-well sample
      source plates. In this work, we describe experiments that establish printing
      performance of the ceramic tips and hybridization experiments that show that DNA
      hybridization is unaffected by the choice of tip material.

PMID- 11591656
TI  - Chromosome-specific single-locus FISH probes allow anchorage of an 1800-marker
      integrated radiation-hybrid/linkage map of the domestic dog genome to all
      chromosomes.
AB  - We present here the first fully integrated, comprehensive map of the canine
      genome, incorporating detailed cytogenetic, radiation hybrid (RH), and meiotic
      information. We have mapped a collection of 266 chromosome-specific cosmid
      clones, each containing a microsatellite marker, to all 38 canine autosomes by
      fluorescence in situ hybridization (FISH). A 1500-marker RH map, comprising 1078
      microsatellites, 320 dog gene markers, and 102 chromosome-specific markers, has
      been constructed using the RHDF5000-2 whole-genome radiation hybrid panel.
      Meiotic linkage analysis was performed, with at least one microsatellite marker
      from each dog autosome on a panel of reference families, allowing one meiotic
      linkage group to be anchored to all 38 dog autosomes. We present a karyotype in
      which each chromosome is identified by one meiotic linkage group and one or more
      RH groups. This updated integrated map, containing a total of 1800 markers,
      covers >90% of the dog genome. Positional selection of anchor clones enabled us,
      for the first time, to orientate nearly all of the integrated groups on each
      chromosome and to evaluate the extent of individual chromosome coverage in the
      integrated genome map. Finally, the inclusion of 320 dog genes into this
      integrated map enhances existing comparative mapping data between human and dog,
      and the 1000 mapped microsatellite markers constitute an invaluable tool with
      which to perform genome scanning studies on pedigrees of interest.

PMID- 11591657
TI  - Molecular cloning and functional analysis of the MutY homolog of Deinococcus
      radiodurans.
AB  - The mutY homolog gene (mutY(Dr)) from Deinococcus radiodurans encodes a 39.4-kDa
      protein consisting of 363 amino acids that displays 35% identity to the
      Escherichia coli MutY (MutY(Ec)) protein. Expressed MutY(Dr) is able to
      complement E. coli mutY mutants but not mutM mutants to reduce the mutation
      frequency. The glycosylase and binding activities of MutY(Dr) with an A/G
      containing substrate are more sensitive to high salt and EDTA concentrations than
      the activities with an A/7,8-dihydro-8-oxoguanine (GO)-containing substrate are.
      Like the MutY(Ec) protein, purified recombinant MutY(Dr) expressed in E. coli has
      adenine glycosylase activity with A/G, A/C, and A/GO mismatches and weak guanine
      glycosylase activity with a G/GO mismatch. However, MutY(Dr) exhibits limited
      apurinic/apyrimidinic lyase activity and can form only weak covalent protein-DNA
      complexes in the presence of sodium borohydride. This may be due to an arginine
      residue that is present in MutY(Dr) at the position corresponding to the position
      of MutY(Ec) Lys142, which forms the Schiff base with DNA. The kinetic parameters
      of MutY(Dr) are similar to those of MutY(Ec). Although MutY(Dr) has similar
      substrate specificity and a binding preference for an A/GO mismatch over an A/G
      mismatch, as MutY(Ec) does, the binding affinities for both mismatches are
      slightly lower for MutY(Dr) than for MutY(Ec). Thus, MutY(Dr) can protect the
      cell from GO mutational effects caused by ionizing radiation and oxidative
      stress.

PMID- 11591658
TI  - Functional characterization of three GlnB homologs in the photosynthetic
      bacterium Rhodospirillum rubrum: roles in sensing ammonium and energy status.
AB  - The GlnB (P(II)) protein, the product of glnB, has been characterized previously
      in the photosynthetic bacterium Rhodospirillum rubrum. Here we describe
      identification of two other P(II) homologs in this organism, GlnK and GlnJ.
      Although the sequences of these three homologs are very similar, the molecules
      have both distinct and overlapping functions in the cell. While GlnB is required
      for activation of NifA activity in R. rubrum, GlnK and GlnJ do not appear to be
      involved in this process. In contrast, either GlnB or GlnJ can serve as a
      critical element in regulation of the reversible ADP ribosylation of
      dinitrogenase reductase catalyzed by the dinitrogenase reductase ADP-ribosyl
      transferase (DRAT)/dinitrogenase reductase-activating glycohydrolase (DRAG)
      regulatory system. Similarly, either GlnB or GlnJ is necessary for normal growth
      on a variety of minimal and rich media, and any of the proteins is sufficient for
      normal posttranslational regulation of glutamine synthetase. Surprisingly, in
      their regulation of the DRAT/DRAG system, GlnB and GlnJ appeared to be responsive
      not only to changes in nitrogen status but also to changes in energy status,
      revealing a new role for this family of regulators in central metabolic
      regulation.

PMID- 11591659
TI  - Azotobacter vinelandii aldehyde dehydrogenase regulated by sigma(54): role in
      alcohol catabolism and encystment.
AB  - Encystment in Azotobacter vinelandii is induced by n-butanol or beta
      hydroxybutyrate (BHB). We identified a gene, encoding an aldehyde dehydrogenase,
      that was named aldA. An aldA mutation impaired bacterial growth on n-butanol,
      ethanol, or hexanol as the sole carbon source. Expression of aldA increased in
      cells shifted from sucrose to n-butanol and was shown to be dependent on the
      alternative sigma(54) factor. A mutation in rpoN encoding the sigma(54) factor
      also impaired growth on alcohols. Encystment on n-butanol, but not on BHB, was
      impaired in aldA or rpoN mutants, indicating that n-butanol is not an inducer of
      encystment by itself but must be catabolized in order to induce encystment.

PMID- 11591660
TI  - Definition of the Bacillus subtilis PurR operator using genetic and bioinformatic
      tools and expansion of the PurR regulon with glyA, guaC, pbuG, xpt-pbuX, yqhZ
      folD, and pbuO.
AB  - The expression of the pur operon, which encodes enzymes of the purine
      biosynthetic pathway in Bacillus subtilis, is subject to control by the purR gene
      product (PurR) and phosphoribosylpyrophosphate. This control is also exerted on
      the purA and purR genes. A consensus sequence for the binding of PurR, named the
      PurBox, has been suggested (M. Kilstrup, S. G. Jessing, S. B. Wichmand-Jorgensen,
      M. Madsen, and D. Nilsson, J. Bacteriol. 180:3900-3906, 1998). To determine
      whether the expression of other genes might be regulated by PurR, we performed a
      search for PurBox sequences in the B. subtilis genome sequence and found several
      candidate PurBoxes. By the use of transcriptional lacZ fusions, five selected
      genes or operons (glyA, yumD, yebB, xpt-pbuX, and yqhZ-folD), all having a
      putative PurBox in their upstream regulatory regions, were found to be regulated
      by PurR. Using a machine-learning algorithm developed for sequence pattern
      finding, we found that all of the genes identified as being PurR regulated have
      two PurBoxes in their upstream control regions. The two boxes are divergently
      oriented, forming a palindromic sequence with the inverted repeats separated by
      16 or 17 nucleotides. A computerized search revealed one additional PurR
      regulated gene, ytiP. The significance of the tandem PurBox motifs was
      demonstrated in vivo by deletion analysis and site-directed mutagenesis of the
      two PurBox sequences located upstream of glyA. All six genes or operons encode
      enzymes or transporters playing a role in purine nucleotide metabolism.
      Functional analysis showed that yebB encodes the previously characterized
      hypoxanthine-guanine permease PbuG and that ytiP encodes another guanine
      hypoxanthine permease and is now named pbuO. yumD encodes a GMP reductase and is
      now named guaC.

PMID- 11591661
TI  - Comparison of DeltarelA strains of Escherichia coli and Salmonella enterica
      serovar Typhimurium suggests a role for ppGpp in attenuation regulation of
      branched-chain amino acid biosynthesis.
AB  - The growth recovery of Escherichia coli K-12 and Salmonella enterica serovar
      Typhimurium DeltarelA mutants were compared after nutritional downshifts
      requiring derepression of the branched-chain amino acid pathways. Because wild
      type E. coli K-12 and S. enterica serovar Typhimurium LT2 strains are defective
      in the expression of the genes encoding the branch point acetohydroxy acid
      synthetase II (ilvGM) and III (ilvIH) isozymes, respectively, DeltarelA
      derivatives corrected for these mutations were also examined. Results indicate
      that reduced expression of the known global regulatory factors involved in
      branched-chain amino acid biosynthesis cannot completely explain the observed
      growth recovery defects of the DeltarelA strains. In the E. coli K-12 MG1655
      DeltarelA background, correction of the preexisting rph-1 allele which causes
      pyrimidine limitations resulted in complete loss of growth recovery. S. enterica
      serovar Typhimurium LT2 DeltarelA strains were fully complemented by elevated
      basal ppGpp levels in an S. enterica serovar Typhimurium LT2 DeltarelA spoT1
      mutant or in a strain harboring an RNA polymerase mutation conferring a reduced
      RNA chain elongation rate. The results are best explained by a dependence on the
      basal levels of ppGpp, which are determined by relA-dependent changes in tRNA
      synthesis resulting from amino acid starvations. Expression of the branched-chain
      amino acid operons is suggested to require changes in the RNA chain elongation
      rate of the RNA polymerase, which can be achieved either by elevation of the
      basal ppGpp levels or, in the case of the E. coli K-12 MG1655 strain, through
      pyrimidine limitations which partially compensate for reduced ppGpp levels. Roles
      for ppGpp in branched-chain amino acid biosynthesis are discussed in terms of
      effects on the synthesis of known global regulatory proteins and current models
      for the control of global RNA synthesis by ppGpp.

PMID- 11591662
TI  - Role of the crc gene in catabolic repression of the Pseudomonas putida GPo1
      alkane degradation pathway.
AB  - Expression of the alkane degradation pathway encoded in the OCT plasmid of
      Pseudomonas putida GPo1 is induced in the presence of alkanes by the AlkS
      regulator, and it is down-regulated by catabolic repression. The catabolic
      repression effect reduces the expression of the two AlkS-activated promoters of
      the pathway, named PalkB and PalkS2. The P. putida Crc protein participates in
      catabolic repression of some metabolic pathways for sugars and nitrogenated
      compounds. Here, we show that Crc has an important role in the catabolic
      repression exerted on the P. putida GPo1 alkane degradation pathway when cells
      grow exponentially in a rich medium. Interestingly, Crc plays little or no role
      on the catabolic repression exerted by some organic acids in a defined medium,
      which shows that these two types of catabolic repression can be genetically
      distinguished. Disruption of the crc gene led to a six- to sevenfold increase in
      the levels of the mRNAs arising from the AlkS-activated PalkB and PalkS2
      promoters in cells growing exponentially in rich medium. This was not due to an
      increase in the half-lives of these mRNAs. Since AlkS activates the expression of
      its own gene and seems to be present in limiting amounts, the higher mRNA levels
      observed in the absence of Crc could arise from an increase in either
      transcription initiation or in the translation efficiency of the alkS mRNA. Both
      alternatives would lead to increased AlkS levels and hence to elevated expression
      of PalkB and PalkS2. High expression of alkS from a heterologous promoter
      eliminated catabolic repression. Our results indicate that catabolic repression
      in rich medium is directed to down-regulate the levels of the AlkS activator. Crc
      would thus modulate, directly or indirectly, the levels of AlkS.

PMID- 11591663
TI  - Pseudomonas aeruginosa PAO1 kills Caenorhabditis elegans by cyanide poisoning.
AB  - In this report we describe experiments to investigate a simple virulence model in
      which Pseudomonas aeruginosa PAO1 rapidly paralyzes and kills the nematode
      Caenorhabditis elegans. Our results imply that hydrogen cyanide is the sole or
      primary toxic factor produced by P. aeruginosa that is responsible for killing of
      the nematode. Four lines of evidence support this conclusion. First, a transposon
      insertion mutation in a gene encoding a subunit of hydrogen cyanide synthase
      (hcnC) eliminated nematode killing. Second, the 17 avirulent mutants examined all
      exhibited reduced cyanide synthesis, and the residual production levels
      correlated with killing efficiency. Third, exposure to exogenous cyanide alone at
      levels comparable to the level produced by PAO1 killed nematodes with kinetics
      similar to those observed with bacteria. The killing was not enhanced if hcnC
      mutant bacteria were present during cyanide exposure. And fourth, a nematode
      mutant (egl-9) resistant to P. aeruginosa was also resistant to killing by
      exogenous cyanide in the absence of bacteria. A model for nematode killing based
      on inhibition of mitochondrial cytochrome oxidase is presented. The action of
      cyanide helps account for the unusually broad host range of virulence of P.
      aeruginosa and may contribute to the pathogenesis in opportunistic human
      infections due to the bacterium.

PMID- 11591664
TI  - Identification and characterization of Tn4656, a novel class II transposon
      carrying a set of toluene-degrading genes from TOL plasmid pWW53.
AB  - It has been reported that the toluene-degrading (xyl) genes from Pseudomonas
      putida plasmid pWW53 are able to translocate to broad-host-range drug resistance
      plasmid RP4, and pWW53-4 is one of the smallest RP4 derivatives (H. Keil, S.
      Keil, R. W. Pickup, and P. A. Williams, J. Bacteriol. 164:887-895, 1985). Our
      investigation of pWW53-4 in this study demonstrated that such a translocated
      region that is 39 kb long is a transposon. This mobile element, Tn4656, was
      classified as a class II transposon since its transposition occurred by a two
      step process: transposase (TnpA)-mediated formation of the cointegrate and
      resolvase (TnpR)-mediated site-specific resolution of the cointegrate at the two
      copies of the res site. The Tn4656 TnpA and TnpR functions encoded in the
      rightmost 4-kb region were found to be exchangeable with those specified by other
      Tn1721-related class II transposons, including another toluene transposon,
      Tn4653. Sequence analysis of the transposition-related genes and sites of Tn4656
      also supported the hypothesis that this transposon is closely related to the
      Tn1721-related transposons. The lower transposition frequency of Tn4656 has been
      suggested to be due to the unique nucleotide sequence of one of the terminal 39
      bp inverted repeats.

PMID- 11591665
TI  - Iron-sulfur flavoprotein (Isf) from Methanosarcina thermophila is the prototype
      of a widely distributed family.
AB  - A total of 35 homologs of the iron-sulfur flavoprotein (Isf) from Methanosarcina
      thermophila were identified in databases. All three domains were represented, and
      multiple homologs were present in several species. An unusually compact cysteine
      motif ligating the 4Fe-4S cluster in Isf is conserved in all of the homologs
      except two, in which either an aspartate or a histidine has replaced the second
      cysteine in the motif. A phylogenetic analysis of Isf homologs identified four
      subgroups, two of which were supported by bootstrap data. Three homologs from
      metabolically and phylogenetically diverse species in the Bacteria and Archaea
      domains (Af3 from Archaeoglobus fulgidus, Cd1 from Clostridium difficile, and Mj2
      from Methanococcus jannaschii) were overproduced in Escherichia coli. Each
      homolog purified as a homodimer, and the UV-visible absorption spectra were
      nearly identical to that of Isf. After reconstitution with iron, sulfide, and
      flavin mononucleotide (FMN) the homologs contained six to eight nonheme iron
      atoms and 1.6 to 1.7 FMN molecules per dimer, suggesting that two 4Fe-4S or 3Fe
      4S clusters and two FMN cofactors were bound to each dimer, which is consistent
      with Isf data. Homologs Af3 and Mj2 were reduced by CO in reactions catalyzed by
      cell extract of acetate-grown M. thermophila, but Cd1 was not. Homologs Af3 and
      Mj2 were reduced by CO in reactions catalyzed by A. fulgidus and M. jannaschii
      cell extracts. Cell extract of Clostridium thermoaceticum catalyzed CO reduction
      of Cd1. Our database sequence analyses and biochemical characterizations indicate
      that Isf is the prototype of a family of iron-sulfur flavoproteins that occur in
      members of all three domains.

PMID- 11591666
TI  - Identification of the partitioning site within the repABC-type replicon of the
      composite Paracoccus versutus plasmid pTAV1.
AB  - The replicator region of composite plasmid pTAV1 of Paracoccus versutus (included
      in mini-replicon pTAV320) belongs to the family of repABC replicons commonly
      found in plasmids harbored by Agrobacterium and Rhizobium spp. The repABC
      replicons encode three genes clustered in an operon, which are involved in
      partitioning (repA and repB) and replication (repC). In order to localize the
      partitioning site of pTAV320, the two identified incompatibility determinants of
      this mini-replicon (inc1, located in the intergenic sequence between repB and
      repC; and inc2, situated downstream of the repC gene) were PCR amplified and used
      together with purified RepB fusion protein (homologous to the type B partitioning
      proteins binding to the partitioning sites) in an electrophoretic mobility shift
      assay. The protein bound only inc2, forming two complexes in a protein
      concentration-dependent manner. The inc2 region contains two long (14-bp)
      repeated sequences (R1 and R2). Disruption of these sequences completely
      eliminates RepB binding ability. R1 and R2 have sequence similarities with
      analogous repeats of another repABC replicon of plasmid pPAN1 of Paracoccus
      pantotrophus DSM 82.5 and with centromeric sequences of the Bacillus subtilis
      chromosome. Excess RepB protein resulted in destabilization of the inc2
      containing plasmid in Escherichia coli. On the other hand, the inc2 region could
      stabilize another unstable replicon in P. versutus when RepA and RepB were
      delivered in trans, proving that this region has centromere-like activity. Thus,
      it was demonstrated that repA, repB, and inc2 constitute a functional system for
      active partitioning of pTAV320.

PMID- 11591667
TI  - Formation of intermediate transcription initiation complexes at pfliD and pflgM
      by sigma(28) RNA polymerase.
AB  - The sigma subunit of prokaryotic RNA polymerase is an important factor in the
      control of transcription initiation. Primary sigma factors are essential for
      growth, while alternative sigma factors are activated in response to various
      stimuli. Expression of class 3 genes during flagellum biosynthesis in Salmonella
      enterica serovar Typhimurium is dependent on the alternative sigma factor
      sigma(28). Previously, a novel mechanism of transcription initiation at the fliC
      promoter by sigma(28) holoenzyme was proposed. Here, we have characterized the
      mechanism of transcription initiation by a holoenzyme carrying sigma(28) at the
      fliD and flgM promoters to determine if the mechanism of initiation observed at
      pfliC is a general phenomenon for all sigma(28)-dependent promoters. Temperature
      dependent footprinting demonstrated that promoter binding properties and low
      temperature open complex formation are similar for pfliC, pfliD, and pflgM.
      However, certain aspects of DNA strand separation and complex stability are
      promoter dependent. Open complexes form in a concerted manner at pflgM, while a
      sequential pattern of open complex formation occurs at pfliD. Open and initiated
      complexes formed by holoenzyme carrying sigma(28) are generally unstable to
      heparin challenge, with the exception of initiated complexes at pflgM, which are
      stable in the presence of nucleoside triphosphates.

PMID- 11591668
TI  - Gonococcal MinD affects cell division in Neisseria gonorrhoeae and Escherichia
      coli and exhibits a novel self-interaction.
AB  - The Min proteins are involved in determining cell division sites in bacteria and
      have been studied extensively in rod-shaped bacteria. We have recently shown that
      the gram-negative coccus Neisseria gonorrhoeae contains a min operon, and the
      present study investigates the role of minD from this operon. A gonococcal minD
      insertional mutant, CJSD1, was constructed and exhibited both grossly abnormal
      cell division and morphology as well as altered cell viability. Western blot
      analysis verified the absence of MinD from N. gonorrhoeae (MinD(Ng)) in this
      mutant. Hence, MinD(Ng) is required for maintaining proper cell division and
      growth in N. gonorrhoeae. Immunoblotting of soluble and insoluble gonococcal cell
      fractions revealed that MinD(Ng) is both cytosolic and associated with the
      insoluble membrane fraction. The joint overexpression of MinC(Ng) and MinD(Ng)
      from a shuttle vector resulted in a significant enlargement of gonococcal cells,
      while cells transformed with plasmids encoding either MinC(Ng) or MinD(Ng) alone
      did not display noticeable morphological changes. These studies suggest that
      MinD(Ng) is involved in inhibiting gonococcal cell division, likely in
      conjunction with MinC(Ng). The alignment of MinD sequences from various bacteria
      showed that the proteins are highly conserved and share several regions of
      identity, including a conserved ATP-binding cassette. The overexpression of
      MinD(Ng) in wild-type Escherichia coli led to cell filamentation, while
      overexpression in an E. coli minD mutant restored a wild-type morphology to the
      majority of cells; therefore, gonococcal MinD is functional across species. Yeast
      two-hybrid studies and gel-filtration and sedimentation equilibrium analyses of
      purified His-tagged MinD(Ng) revealed a novel MinD(Ng) self-interaction. We have
      also shown by yeast two-hybrid analysis that MinD from E. coli interacts with
      itself and with MinD(Ng). These results indicate that MinD(Ng) is required for
      maintaining proper cell division and growth in N. gonorrhoeae and suggests that
      the self-interaction of MinD may be important for cell division site selection
      across species.

PMID- 11591669
TI  - Cloning, sequencing, and characterization of the iturin A operon.
AB  - Bacillus subtilis RB14 is a producer of the antifungal lipopeptide iturin A.
      Using a transposon, we identified and cloned the iturin A synthetase operon of
      RB14, and the sequence of this operon was also determined. The iturin A operon
      spans a region that is more than 38 kb long and is composed of four open reading
      frames, ituD, ituA, ituB, and ituC. The ituD gene encodes a putative malonyl
      coenzyme A transacylase, whose disruption results in a specific deficiency in
      iturin A production. The second gene, ituA, encodes a 449-kDa protein that has
      three functional modules homologous to fatty acid synthetase, amino acid
      transferase, and peptide synthetase. The third gene, ituB, and the fourth gene,
      ituC, encode 609- and 297-kDa peptide synthetases that harbor four and two amino
      acid modules, respectively. Mycosubtilin, which is produced by B. subtilis ATCC
      6633, has almost the same structure as iturin A, but the amino acids at positions
      6 and 7 in the mycosubtilin sequence are D-Ser-->L-Asn, while in iturin A these
      amino acids are inverted (i.e., D-Asn-->L-Ser). Comparison of the amino acid
      sequences encoded by the iturin A operon and the mycosubtilin operon revealed
      that ituD, ituA, and ituB have high levels of homology to the counterpart genes
      fenF (79%), mycA (79%), and mycB (79%), respectively. Although the overall level
      of homology of the amino acid sequences encoded by ituC and mycC, the counterpart
      of ituC, is relatively low (64%), which indicates that there is a difference in
      the amino acid sequences of the two lipopeptides, the levels of homology between
      the putative serine adenylation domains and between the asparagine adenylation
      domains in the two synthetases are high (79 and 80%, respectively), implying that
      there is an intragenic domain change in the synthetases. The fact that the
      flanking sequence of the iturin A synthetase coding region was highly homologous
      to the flanking sequence that of xynD of B. subtilis 168 and the fact that the
      promoter of the iturin A operon which we identified was also conserved in an
      upstream sequence of xynD imply that horizontal transfer of this operon occurred.
      When the promoter was replaced by the repU promoter of the plasmid pUB110
      replication protein, production of iturin A increased threefold.

PMID- 11591670
TI  - DNA inversion in the tail fiber gene alters the host range specificity of
      carotovoricin Er, a phage-tail-like bacteriocin of phytopathogenic Erwinia
      carotovora subsp. carotovora Er.
AB  - Carotovoricin Er is a phage-tail-like bacteriocin produced by Erwinia carotovora
      subsp. carotovora strain Er, a causative agent for soft rot disease in plants.
      Here we studied binding and killing spectra of carotovoricin Er preparations for
      various strains of the bacterium (strains 645Ar, EC-2, N786, and P7) and found
      that the preparations contain two types of carotovoricin Er with different host
      specificities; carotovoricin Era possessing a tail fiber protein of 68 kDa killed
      strains 645Ar and EC-2, while carotovoricin Erb with a tail fiber protein of 76
      kDa killed strains N786 and P7. The tail fiber proteins of 68 and 76 kDa had
      identical N-terminal amino acid sequences for at least 11 residues. A search of
      the carotovoricin Er region in the chromosome of strain Er indicated the
      occurrence of a DNA inversion system for the tail fiber protein consisting of (i)
      two 26-bp inverted repeats inside and downstream of the tail fiber gene that
      flank a 790-bp fragment and (ii) a putative DNA invertase gene with a 90-bp
      recombinational enhancer sequence. In fact, when a 1,400-bp region containing the
      790-bp fragment was amplified by a PCR using the chromosomal DNA of strain Er as
      the template, both the forward and the reverse nucleotide sequences of the 790-bp
      fragment were detected. DNA inversion of the 790-bp fragment also occurred in
      Escherichia coli DH5alpha when two compatible plasmids carrying either the 790-bp
      fragment or the invertase gene were cotransformed into the bacterium.
      Furthermore, hybrid carotovoricin CGE possessing the tail fiber protein of 68 or
      76 kDa exhibited a host range specificity corresponding to that of carotovoricin
      Era or Erb, respectively. Thus, a DNA inversion altered the C-terminal part of
      the tail fiber protein of carotovoricin Er, altering the host range specificity
      of the bacteriocin.

PMID- 11591671
TI  - Heat-shock-induced proteins from Myxococcus xanthus.
AB  - Optimal conditions for two-dimensional gel electrophoresis of total cellular
      proteins from Myxococcus xanthus were established. Using these conditions, we
      analyzed protein patterns of heat-shocked M. xanthus cells. Eighteen major spots
      and 15 minor spots were found to be induced by heat shock. From N-terminal
      sequences of 15 major spots, DnaK, GroEL, GroES, alkyl hydroperoxide reductase,
      aldehyde dehydrogenase, succinyl coenzyme A (CoA) synthetase, 30S ribosomal
      protein S6, and ATP synthase alpha subunit were identified. Three of the 18 major
      spots had an identical N-terminal sequence, indicating that they may be different
      forms of the same protein. Although a DnaK homologue, SglK, has been identified
      in M. xanthus (R. M. Weimer, C. Creghton, A. Stassinopoulos, P. Youderian, and P.
      L. Hartzell, J. Bacteriol. 180:5357-5368, 1998; Z. Yang, Y. Geng, and W. Shi, J.
      Bacteriol. 180:218-224, 1998), SglK was not induced by heat shock. In addition,
      there were seven substitutions within the N-terminal 30-residue sequence of the
      newly identified DnaK. This is the first report to demonstrate that succinyl CoA
      synthetase, 30S ribosomal protein S6, and ATP synthase alpha subunit are heat
      shock inducible.

PMID- 11591672
TI  - DNA as a nutrient: novel role for bacterial competence gene homologs.
AB  - The uptake and stable maintenance of extracellular DNA, genetic transformation,
      is universally recognized as a major force in microbial evolution. We show here
      that extracellular DNA, both homospecific and heterospecific, can also serve as
      the sole source of carbon and energy supporting microbial growth. Mutants unable
      to consume DNA suffer a significant loss of fitness during stationary-phase
      competition. In Escherichia coli, the use of DNA as a nutrient depends on
      homologs of proteins involved in natural genetic competence and transformation in
      Haemophilus influenzae and Neisseria gonorrhoeae. Homologs of these E. coli genes
      are present in many members of the gamma subclass of Proteobacteria, suggesting
      that the mechanisms for consumption of DNA may have been widely conserved during
      evolution.

PMID- 11591673
TI  - Surface display of recombinant proteins on Bacillus subtilis spores.
AB  - We developed a novel surface display system based on the use of bacterial spores.
      A protein of the Bacillus subtilis spore coat, CotB, was found to be located on
      the spore surface and used as fusion partner to express the 459-amino-acid C
      terminal fragment of the tetanus toxin (TTFC). Western, dot blot and fluorescent
      activated cell sorting analyses were used to monitor TTFC surface expression on
      purified spores. We estimated that more than 1.5 x 10(3) TTFC molecules were
      exposed on the surface of each spore and recognized by TTFC-specific antibodies.
      The efficient surface presentation of the heterologous protein, together with the
      simple purification procedure and the high stability and safety record of B.
      subtilis spores, makes this spore-based display system a potentially powerful
      approach for surface expression of bioactive molecules.

PMID- 11591674
TI  - Chemical structure of a novel aminophospholipid from Hydrogenobacter thermophilus
      strain TK-6.
AB  - The phospholipid composition of Hydrogenobacter thermophilus strain TK-6, an
      obligately chemolithoautotrophic, extremely thermophilic hydrogen bacterium, was
      analyzed. Two of four phospholipids detected from the strain were assumed to be
      phosphatidylinositol and phosphatidylglycerol. An aminophospholipid named PX,
      whose content among the phospholipids was 65%, was found to have a novel chemical
      structure by analysis of the dilyso form with nuclear magnetic resonance and fast
      atom bombardment-mass spectrometry (FAB-MS) and by analysis of the intact PX with
      FAB-MS as 1,2-diacyl-3-O-(phospho-2'-O-(1'-amino)-2',3',4',5'-pentanetetrol)-sn
      glycerol. Structurally similar phospholipids have been identified in
      Methanospirillum hungatei, Methanolacinia paynteri, and Methanogenium cariaci,
      which all belong to the Archaea.

PMID- 11591675
TI  - Contributions of UP elements and the transcription factor FIS to expression from
      the seven rrn P1 promoters in Escherichia coli.
AB  - The high activity of the rrnB P1 promoter in Escherichia coli results from a cis
      acting DNA sequence, the UP element, and a trans-acting transcription factor,
      FIS. In this study, we examine the effects of FIS and the UP element at the other
      six rrn P1 promoters. We find that UP elements are present at all of the rrn P1
      promoters, but they make different relative contributions to promoter activity.
      Similarly, FIS binds upstream of, and activates, all seven rrn P1 promoters but
      to different extents. The total number of FIS binding sites, as well as their
      positions relative to the transcription start site, differ at each rrn P1
      promoter. Surprisingly, the FIS sites upstream of site I play a much larger role
      in transcription from most rrn P1 promoters compared to rrnB P1. Our studies
      indicate that the overall activities of the seven rrn P1 promoters are similar,
      and the same contributors are responsible for these high activities, but these
      inputs make different relative contributions and may act through slightly
      different mechanisms at each promoter. These studies have implications for the
      control of gene expression of unlinked multigene families.

PMID- 11591676
TI  - Regulation of rRNA transcription correlates with nucleoside triphosphate sensing.
AB  - We have previously shown that the activity of the Escherichia coli rRNA promoter
      rrnB P1 in vitro depends on the concentration of the initiating nucleotide, ATP,
      and can respond to changes in ATP pools in vivo. We have proposed that this
      nucleoside triphosphate (NTP) sensing might contribute to regulation of rRNA
      transcription. To test this model, we have measured the ATP requirements for
      transcription from 11 different rrnB P1 core promoter mutants in vitro and
      compared them with the regulatory responses of the same promoters in vivo. The
      seven rrnB P1 variants that required much lower ATP concentrations than the wild
      type promoter for efficient transcription in vitro were defective for response to
      growth rate changes in vivo (growth rate-dependent regulation). In contrast, the
      four variants requiring high ATP concentrations in vitro (like the wild-type
      promoter) were regulated with the growth rate in vivo. We also observed a
      correlation between NTP sensing in vitro and the response of the promoters in
      vivo to deletion of the fis gene (an example of homeostatic control), although
      this relationship was not as tight as for growth rate-dependent regulation. We
      conclude that the kinetic features responsible for the high ATP concentration
      dependence of the rrnB P1 promoter in vitro are responsible, at least in part,
      for the promoter's regulation in vivo, consistent with the model in which rrnB P1
      promoter activity can be regulated by changes in NTP pools in vivo (or by
      hypothetical factors that work at the same kinetic steps that make the promoter
      sensitive to NTPs).

PMID- 11591677
TI  - Regulation of D-alanyl-lipoteichoic acid biosynthesis in Streptococcus agalactiae
      involves a novel two-component regulatory system.
AB  - The dlt operon of gram-positive bacteria comprises four genes (dltA, dltB, dltC,
      and dltD) that catalyze the incorporation of D-alanine residues into the
      lipoteichoic acids (LTAs). In this work, we characterized the dlt operon of
      Streptococcus agalactiae, which, in addition to the dltA to dltD genes, included
      two regulatory genes, designated dltR and dltS, located upstream of dltA. The
      dltR gene encodes a 224-amino-acid putative response regulator belonging to the
      OmpR family of regulatory proteins. The dltS gene codes for a 395-amino-acid
      putative histidine kinase thought to be involved in the sensing of environmental
      signals. The dlt operon of S. agalactiae is mainly transcribed from the P(dltR)
      promoter, which directs synthesis of a 6.5-kb transcript encompassing dltR, dltS,
      dltA, dltB, dltC, and dltD, and from a weaker promoter, P(dltA), which is located
      in the 3' extremity of dltS. We demonstrate that P(dltR), but not P(dlA), is
      activated by DltR in the presence of DltS in D-Ala-deficient LTA mutants
      resulting from insertional inactivation of the dltA gene, which encodes the
      cytoplasmic D-alanine-D-alanyl carrier ligase DltA. Expression of the dlt operon
      does not require DltR and DltS, since the basal activity of P(dltR) is high,
      being 20-fold that of the constitutive promoter P(aphA-3) which directs synthesis
      of the kanamycin resistance gene aphA-3 in various gram-positive bacteria. We
      hypothesize that the role of DltR and DltS in the control of expression of the
      dlt operon is to maintain the level of D-Ala esters in LTAs at a constant and
      appropriate value whatever the environmental conditions. The DltA(-) mutant
      displayed the ability to form clumps in standing culture and exhibited an
      increased susceptibility to the cationic antimicrobial polypeptide colistin.

PMID- 11591678
TI  - Production of two proteins encoded by the Bacteroides mobilizable transposon NBU1
      correlates with time-dependent accumulation of the excised NBu1 circular form.
AB  - NBU1 is a mobilizable transposon that excises from the Bacteroides chromosome to
      form a double-stranded circular transfer intermediate. Excision is triggered by
      exposure of the bacteria to tetracycline. Accordingly, we expected that the
      expression of NBU1 genes would be induced by tetracycline. To test this
      hypothesis, antibodies that recognized two NBU1-encoded proteins, PrmN1 and
      MobN1, were used to monitor production of these proteins. PrmN1 is essential for
      excision, and MobN1 is essential for transfer of the excised circular form. At
      first, expression of the genes encoding these two proteins appeared to be
      regulated by tetracycline, because the proteins were detectable on Western blots
      only after the cells were exposed to tetracycline. However, when the prmN1 gene
      and/or the mobN1 gene was cloned on a multicopy plasmid, production of the
      protein was constitutive. Initially, we assumed that the constitutive expression
      was due to loss of a repressor protein that was encoded by one of the other genes
      on NBU1. Deletions or insertions in the other genes (orf2 and orf3) on NBU1 and
      various integrated NBU1 derivatives abolished production of PrmN1 and MobN1. This
      is the opposite of what should have happened if one or both of these genes
      encoded a repressor. A second possibility was that when NBU1 excised, it
      replicated transiently, increasing the gene dosage of prmN1 and mobN1 and thereby
      producing enough PrmN1 and MobN1 for these proteins to become detectable. In
      fact, after the cells entered late exponential phase the copy number of NBU1
      increased to 2 to 3 copies per cell. Production of PrmN1 and MobN1 showed a
      similar pattern. Any mutation in NBU1 that decreased or prevented excision also
      prevented elevated production of these two proteins. Our results show that the
      apparent tetracycline dependence of the production of PrmN1 and MobN1 is due to a
      growth phase- or time-dependent increase in the number of copies of the NBU1
      circular form.

PMID- 11591679
TI  - Interactive control of Rhodobacter capsulatus redox-balancing systems during
      phototrophic metabolism.
AB  - In nonsulfur purple bacteria, redox homeostasis is achieved by the coordinate
      control of various oxidation-reduction balancing mechanisms during phototrophic
      anaerobic respiration. In this study, the ability of Rhodobacter capsulatus to
      maintain a balanced intracellular oxidation-reduction potential was considered;
      in addition, interrelationships between the control of known redox-balancing
      systems, the Calvin-Benson-Bassham, dinitrogenase and dimethyl sulfoxide
      reductase systems, were probed in strains grown under both photoheterotrophic and
      photoautotrophic growth conditions. By using cbb(I) (cbb form I operon)-, cbb(II)
      , nifH-, and dorC-reporter gene fusions, it was demonstrated that each redox
      balancing system responds to specific metabolic circumstances under phototrophic
      growth conditions. In specific mutant strains of R. capsulatus, expression of
      both the Calvin-Benson-Bassham and dinitrogenase systems was influenced by
      dimethyl sulfoxide respiration. Under photoheterotrophic growth conditions,
      coordinate control of redox-balancing systems was further manifested in ribulose
      1,5-bisphosphate carboxylase/oxygenase and phosphoribulokinase deletion strains.
      These findings demonstrated the existence of interactive control mechanisms that
      govern the diverse means by which R. capsulatus maintains redox poise during
      photoheterotrophic and photoautotrophic growth.

PMID- 11591680
TI  - TspO as a modulator of the repressor/antirepressor (PpsR/AppA) regulatory system
      in Rhodobacter sphaeroides 2.4.1.
AB  - The TspO outer membrane protein of Rhodobacter sphaeroides has been shown to be
      involved in controlling the transcription of a number of genes which encode
      enzymes involved in photopigment biosynthesis and the puc operon. The display of
      regulated genes appears identical to those genes encompassing the PpsR/AppA
      repressor/antirepressor regulon, although the effect of TspO is modest relative
      to that of PpsR/AppA. To directly address the hypothesis that TspO is effective
      through the PpsR/AppA system, we constructed mutant strains with mutations in
      both tspO and appA. In all cases, the phenotypes examined resembled those of the
      appA lesion by itself, leading us to conclude that TspO works through or
      modulates the PpsR/AppA system and acts upstream of the site of action of these
      regulatory proteins. In earlier publications, we had suggested that TspO is
      involved in the efflux of a certain intermediate(s) of the porphyrin biosynthesis
      pathway and that transcriptional regulation of target gene expression could be
      explained by the accumulation of a coactivator of AppA function. Although the
      data reported here do not precisely identify this coactivator, they lend support
      to this hypothesis. We discuss the importance of this form of gene control as the
      result of the recent extension of the TspO system to Sinorhizobium meliloti, as
      described by Davey and de Bruijn (M. E. Davey and F. J. de Bruijn, Appl. Environ.
      Microbiol. 66:5353-5359, 2000). It is therefore possible that this system
      constitutes a more widely, although not universally, demonstrated form of gene
      regulation.

PMID- 11591681
TI  - An archaeal photosignal-transducing module mediates phototaxis in Escherichia
      coli.
AB  - Halophilic archaea, such as Halobacterium salinarum and Natronobacterium
      pharaonis, alter their swimming behavior by phototaxis responses to changes in
      light intensity and color using visual pigment-like sensory rhodopsins (SRs). In
      N. pharaonis, SRII (NpSRII) mediates photorepellent responses through its
      transducer protein, NpHtrII. Here we report the expression of fusions of NpSRII
      and NpHtrII and fusion hybrids with eubacterial cytoplasmic domains and analyze
      their function in vivo in haloarchaea and in eubacteria. A fusion in which the C
      terminus of NpSRII is connected by a short flexible linker to NpHtrII is active
      in phototaxis signaling for H. salinarum, showing that the fusion does not
      inhibit functional receptor-transducer interactions. We replaced the cytoplasmic
      portions of this fusion protein with the cytoplasmic domains of Tar and Tsr,
      chemotaxis transducers from enteric eubacteria. Purification of the fusion
      protein from H. salinarum and Tar fusion chimera from Escherichia coli membranes
      shows that the proteins are not cleaved and exhibit absorption spectra
      characteristic of wild-type membranes. Their photochemical reaction cycles in H.
      salinarum and E. coli membranes, respectively, are similar to those of native
      NpSRII in N. pharaonis. These fusion chimeras mediate retinal-dependent
      phototaxis responses by Escherichia coli, establishing that the nine-helix
      membrane portion of the receptor-transducer complex is a modular functional unit
      able to signal in heterologous membranes. This result confirms a current model
      for SR-Htr signal transduction in which the Htr transducers are proposed to
      interact physically and functionally with their cognate sensory rhodopsins via
      helix-helix contacts between their transmembrane segments.

PMID- 11591682
TI  - Peroxisomal catalase in the methylotrophic yeast Candida boidinii: transport
      efficiency and metabolic significance.
AB  - In this study we cloned CTA1, the gene encoding peroxisomal catalase, from the
      methylotrophic yeast Candida boidinii and studied targeting of the gene product,
      Cta1p, into peroxisomes by using green fluorescent protein (GFP) fusion proteins.
      A strain from which CTA1 was deleted (cta1Delta strain) showed marked growth
      inhibition when it was grown on the peroxisome-inducing carbon sources methanol,
      oleate, and D-alanine, indicating that peroxisomal catalase plays an important
      nonspecific role in peroxisomal metabolism. Cta1p carries a peroxisomal targeting
      signal type 1 (PTS1) motif, -NKF, in its carboxyl terminus. Using GFP fusion
      proteins, we found that (i) Cta1p is transported to peroxisomes via its PTS1
      motif, -NKF; (ii) peroxisomal localization is necessary for Cta1p to function
      physiologically; and (iii) Cta1p is bimodally distributed between the cytosol and
      peroxisomes in methanol-grown cells but is localized exclusively in peroxisomes
      in oleate- and D-alanine-grown cells. In contrast, the fusion protein GFP-AKL
      (GFP fused to another typical PTS1 sequence, -AKL), in the context of CbPmp20 and
      D-amino acid oxidase, was found to localize exclusively in peroxisomes. A yeast
      two-hybrid system analysis suggested that the low transport efficiency of the 
      NKF sequence is due to a level of interaction between the -NKF sequence and the
      PTS1 receptor that is lower than the level of interaction with the AKL sequence.
      Furthermore, GFP-Cta1pDeltankf coexpressed with Cta1p was successfully localized
      in peroxisomes, suggesting that the oligomer was formed prior to peroxisome
      import and that it is not necessary for all four subunits to possess a PTS motif.
      Since the main physiological function of catalase is degradation of H2O2,
      suboptimal efficiency of catalase import may confer an evolutionary advantage. We
      suggest that the PTS1 sequence, which is found in peroxisomal catalases, has
      evolved in such a way as to give a higher priority for peroxisomal transport to
      peroxisomal enzymes other than to catalases (e.g., oxidases), which require a
      higher level of peroxisomal transport efficiency.

PMID- 11591683
TI  - Conditional-replication, integration, excision, and retrieval plasmid-host
      systems for gene structure-function studies of bacteria.
AB  - We have developed a series of powerful and versatile conditional-replication,
      integration, and modular (CRIM) plasmids. CRIM plasmids can be replicated at
      medium or high copy numbers in different hosts for making gene (or mutant)
      libraries. They can be integrated in single copies into the chromosomes of
      Escherichia coli and related bacteria to study gene function under normal
      physiological conditions. They can be excised from the chromosome, e.g., to
      verify that phenotypes are caused by their presence. Furthermore, they can be
      retrieved singly or en masse for subsequent molecular analyses. CRIM plasmids are
      integrated into the chromosome by site-specific recombination at one of five
      different phage attachment sites. Integrants are selected as antibiotic-resistant
      transformations. Since CRIM plasmids encode different forms of resistance,
      several can be used together in the same cell for stable expression of complex
      metabolic or regulatory pathways from diverse sources. Following integration,
      integrants are stably maintained in the absence of antibiotic selection. Each
      CRIM plasmid has a polylinker or one of several promoters for ectopic expression
      of the inserted DNA. Their modular design allows easy construction of new
      variants with different combinations of features. We also report a series of
      easily curable, low-copy-number helper plasmids encoding all the requisite Int
      proteins alone or with the respective Xis protein. These helper plasmids
      facilitate integration, excision ("curing"), or retrieval of the CRIM plasmids.

PMID- 11591684
TI  - Homologues of neisserial heme oxygenase in gram-negative bacteria: degradation of
      heme by the product of the pigA gene of Pseudomonas aeruginosa.
AB  - The oxidative cleavage of heme to release iron is a mechanism by which some
      bacterial pathogens can utilize heme as an iron source. The pigA gene of
      Pseudomonas aeruginosa is shown to encode a heme oxygenase protein, which was
      identified in the genome sequence by its significant homology (37%) with HemO of
      Neisseria meningitidis. When the gene encoding the neisserial heme oxygenase,
      hemO, was replaced with pigA, we demonstrated that pigA could functionally
      replace hemO and allow for heme utilization by neisseriae. Furthermore, when pigA
      was disrupted by cassette mutagenesis in P. aeruginosa, heme utilization was
      defective in iron-poor media supplemented with heme. This defect could be
      restored both by the addition of exogenous FeSO4, indicating that the mutant did
      not have a defect in iron metabolism, and by in trans complementation with pigA
      from a plasmid with an inducible promoter. The PigA protein was purified by ion
      exchange chromotography. The UV-visible spectrum of PigA reconstituted with heme
      showed characteristics previously reported for other bacterial and mammalian heme
      oxygenases. The heme-PigA complex could be converted to ferric biliverdin in the
      presence of ascorbate, demonstrating the need for an exogenous reductant.
      Acidification and high-performance liquid chromatography analysis of the
      ascorbate reduction products identified a major product of biliverdin IX-beta.
      This differs from the previously characterized heme oxygenases in which
      biliverdin IX-alpha is the typical product. We conclude that PigA is a heme
      oxygenase and may represent a class of these enzymes with novel regiospecificity.

PMID- 11591685
TI  - Structures of bacterial flagellar motors from two FliF-FliG gene fusion mutants.
AB  - Flagella purified from Salmonella enterica serovar Typhimurium contain FliG,
      FliM, and FliN, cytoplasmic proteins that are important in torque generation and
      switching, and FliF, a transmembrane structural protein. The motor portion of the
      flagellum (the basal body complex) has a cytoplasmic C ring and a transmembrane M
      ring. Incubation of purified basal bodies at pH 4.5 removed FliM and FliN but not
      FliG or FliF. These basal bodies lacked C rings but had intact M rings,
      suggesting that FliM and FliN are part of the C ring but not a detectable part of
      the M ring. Incubation of basal bodies at pH 2.5 removed FliG, FliM, and FliN but
      not FliF. These basal bodies lacked the C ring, and the cytoplasmic face of the M
      ring was altered, suggesting that FliG makes up at least part of the cytoplasmic
      face of the M ring. Further insights into FliG were obtained from cells
      expressing a fusion protein of FliF and FliG. Flagella from these mutants still
      rotated but cells were not chemotactic. One mutant is a full-length fusion of
      FliF and FliG; the second mutant has a deletion lacking the last 56 residues of
      FliF and the first 94 residues of FliG. In the former, C rings appeared complete,
      but a portion of the M ring was shifted to higher radius. The C-ring-M-ring
      interaction appeared to be altered. In basal bodies with the fusion-deletion
      protein, the C ring was smaller in diameter, and one of its domains occupied
      space vacated by missing portions of FliF and FliG.

PMID- 11591686
TI  - Bacterial two-hybrid analysis of interactions between region 4 of the sigma(70)
      subunit of RNA polymerase and the transcriptional regulators Rsd from Escherichia
      coli and AlgQ from Pseudomonas aeruginosa.
AB  - A number of transcriptional regulators mediate their effects through direct
      contact with the sigma(70) subunit of Escherichia coli RNA polymerase (RNAP). In
      particular, several regulators have been shown to contact a C-terminal portion of
      sigma(70) that harbors conserved region 4. This region of sigma contains a
      putative helix-turn-helix DNA-binding motif that contacts the -35 element of
      sigma(70)-dependent promoters directly. Here we report the use of a recently
      developed bacterial two-hybrid system to study the interaction between the
      putative anti-sigma factor Rsd and the sigma(70) subunit of E. coli RNAP. Using
      this system, we found that Rsd can interact with an 86-amino-acid C-terminal
      fragment of sigma(70) and also that amino acid substitution R596H, within region
      4 of sigma(70), weakens this interaction. We demonstrated the specificity of this
      effect by showing that substitution R596H does not weaken the interaction between
      sigma and two other regulators shown previously to contact region 4 of sigma(70).
      We also demonstrated that AlgQ, a homolog of Rsd that positively regulates
      virulence gene expression in Pseudomonas aeruginosa, can contact the C-terminal
      region of the sigma(70) subunit of RNAP from this organism. We found that amino
      acid substitution R600H in sigma(70) from P. aeruginosa, corresponding to the
      R596H substitution in E. coli sigma(70), specifically weakens the interaction
      between AlgQ and sigma(70). Taken together, our findings suggest that Rsd and
      AlgQ contact similar surfaces of RNAP present in region 4 of sigma(70) and
      probably regulate gene expression through this contact.

PMID- 11591687
TI  - Catalytic function of an alpha/beta hydrolase is required for energy stress
      activation of the sigma(B) transcription factor in Bacillus subtilis.
AB  - The general stress response of Bacillus subtilis is controlled by the sigma(B)
      transcription factor, which is activated in response to diverse energy and
      environmental stresses. These two classes of stress are transmitted by separate
      signaling pathways which converge on the direct regulators of sigma(B), the RsbV
      anti-anti-sigma factor and the RsbW anti-sigma factor. The energy signaling
      branch involves the RsbP phosphatase, which dephosphorylates RsbV in order to
      trigger the general stress response. The rsbP structural gene lies downstream
      from rsbQ in a two-gene operon. Here we identify the RsbQ protein as a required
      positive regulator inferred to act in concert with the RsbP phosphatase. RsbQ
      bound RsbP in the yeast two-hybrid system, and a large in-frame deletion in rsbQ
      had the same phenotype as a null allele of rsbP-an inability to activate sigma(B)
      in response to energy stress. Genetic complementation studies indicated that this
      phenotype was not due to a polar effect of the rsbQ alteration on rsbP. The
      predicted rsbQ product is a hydrolase or acyltransferase of the alpha/beta fold
      superfamily, members of which catalyze a wide variety of reactions. Notably,
      substitutions in the presumed catalytic triad of RsbQ also abolished the energy
      stress response but had no detectable effect on RsbQ structure, synthesis, or
      stability. We conclude that the catalytic activity of RsbQ is an essential
      constituent of the energy stress signaling pathway.

PMID- 11591688
TI  - The coxBAC operon encodes a cytochrome c oxidase required for heterotrophic
      growth in the cyanobacterium Anabaena variabilis strain ATCC 29413.
AB  - Three genes, coxB, coxA, and coxC, found in a clone from a gene library of the
      cyanobacterium Anabaena variabilis strain ATCC 29413, were identified by
      hybridization with an oligonucleotide specific for aa(3)-type cytochrome c
      oxidases. Deletion of these genes from the genome of A. variabilis strain ATCC
      29413 FD yielded strain CSW1, which displayed no chemoheterotrophic growth and an
      impaired cytochrome c oxidase activity. Photoautotrophic growth of CSW1, however,
      was unchanged, even with dinitrogen as the nitrogen source. A higher cytochrome c
      oxidase activity was detected in membrane preparations from dinitrogen-grown CSW1
      than from nitrate-grown CSW1, but comparable activities of respiratory oxygen
      uptake were found in the wild type and in CSW1. Our data indicate that the
      identified cox gene cluster is essential for fructose-dependent growth in the
      dark, but not for growth on dinitrogen, and that other terminal respiratory
      oxidases are expressed in this cyanobacterium. Transcription analysis showed that
      coxBAC constitutes an operon which is expressed from two transcriptional start
      points. The use of one of them was stimulated by fructose.

PMID- 11591689
TI  - Localization of cold shock proteins to cytosolic spaces surrounding nucleoids in
      Bacillus subtilis depends on active transcription.
AB  - Using immunofluorescence microscopy and a fusion of a cold shock protein (CSP),
      CspB, to green fluorescent protein (GFP), we showed that in growing cells
      Bacillus subtilis CSPs specifically localize to cytosolic regions surrounding the
      nucleoid. The subcellular localization of CSPs is influenced by the structure of
      the nucleoid. Decondensed chromosomes in smc mutant cells reduced the sizes of
      the regions in which CSPs localized, while cold shock-induced chromosome
      compaction was accompanied by an expansion of the space in which CSPs were
      present. As a control, histone-like protein HBsu localized to the nucleoids,
      while beta-galactosidase and GFP were detectable throughout the cell. After
      inhibition of translation, CspB-GFP was still present around the nucleoids in a
      manner similar to that in cold-shocked cells. However, in stationary-phase cells
      and after inhibition of transcription, CspB was distributed throughout the cell,
      indicating that specific localization of CspB depends on active transcription and
      is not due to simple exclusion from the nucleoid. Furthermore, we observed that
      nucleoids are more condensed and frequently abnormal in cspB cspC and cspB cspD
      double-mutant cells. This suggests that the function of CSPs affects chromosome
      structure, probably through coupling of transcription to translation, which is
      thought to decondense nucleoids. In addition, we found that cspB cspD and cspB
      cspC double mutants are defective in sporulation, with a block at or before stage
      0. Interestingly, CspB and CspC are depleted from the forespore compartment but
      not from the mother cell. In toto, our findings suggest that CSPs localize to
      zones of newly synthesized RNA, coupling transcription with initiation of
      translation.

PMID- 11591690
TI  - Genetic analysis of the Sinorhizobium meliloti BacA protein: differential effects
      of mutations on phenotypes.
AB  - Sinorhizobium meliloti strains lacking BacA function are impaired in symbiosis
      with alfalfa host plants and display altered sensitivities to a number of
      compounds relative to wild-type strains. With the goal of finding clues to the
      currently unknown biological function(s) of BacA, we carried out a genetic
      analysis to determine which amino acids are critical for protein function and to
      attempt to ascertain whether the multiple phenotypes that result from a bacA-null
      allele were the result of a common cause or whether BacA has multiple functions.
      We have created a set of 20 site-directed mutants in which selected individual
      amino acids in bacA were replaced with glycine residues. The resulting mutants
      were characterized to determine how the various amino acid changes affected a
      number of phenotypes associated with loss of BacA function. Mutants H165G, W182G,
      D198G, and R284G had null phenotypes for all functions assayed, while mutants
      W57G, S83G, S231G, and K350G were indistinguishable from wild-type strains. The
      remaining 12 site-directed mutants demonstrate mixed phenotypic characteristics
      and fall into a number of distinctly different groups. These observations may be
      consistent with a role for BacA in multiple, nonoverlapping functions.

PMID- 11591691
TI  - Functional analysis of genes for biosynthesis of pyocyanin and phenazine-1
      carboxamide from Pseudomonas aeruginosa PAO1.
AB  - Two seven-gene phenazine biosynthetic loci were cloned from Pseudomonas
      aeruginosa PAO1. The operons, designated phzA1B1C1D1E1F1G1 and phzA2B2C2D2E2F2G2,
      are homologous to previously studied phenazine biosynthetic operons from
      Pseudomonas fluorescens and Pseudomonas aureofaciens. Functional studies of
      phenazine-nonproducing strains of fluorescent pseudomonads indicated that each of
      the biosynthetic operons from P. aeruginosa is sufficient for production of a
      single compound, phenazine-1-carboxylic acid (PCA). Subsequent conversion of PCA
      to pyocyanin is mediated in P. aeruginosa by two novel phenazine-modifying genes,
      phzM and phzS, which encode putative phenazine-specific methyltransferase and
      flavin-containing monooxygenase, respectively. Expression of phzS alone in
      Escherichia coli or in enzymes, pyocyanin-nonproducing P. fluorescens resulted in
      conversion of PCA to 1-hydroxyphenazine. P. aeruginosa with insertionally
      inactivated phzM or phzS developed pyocyanin-deficient phenotypes. A third
      phenazine-modifying gene, phzH, which has a homologue in Pseudomonas
      chlororaphis, also was identified and was shown to control synthesis of phenazine
      1-carboxamide from PCA in P. aeruginosa PAO1. Our results suggest that there is a
      complex pyocyanin biosynthetic pathway in P. aeruginosa consisting of two core
      loci responsible for synthesis of PCA and three additional genes encoding unique
      enzymes involved in the conversion of PCA to pyocyanin, 1-hydroxyphenazine, and
      phenazine-1-carboxamide.

PMID- 11591693
TI  - Cloning and characterization of a gene cluster for cyclododecanone oxidation in
      Rhodococcus ruber SC1.
AB  - Biological oxidation of cyclic ketones normally results in formation of the
      corresponding dicarboxylic acids, which are further metabolized in the cell.
      Rhodococcus ruber strain SC1 was isolated from an industrial wastewater
      bioreactor that was able to utilize cyclododecanone as the sole carbon source. A
      reverse genetic approach was used to isolate a 10-kb gene cluster containing all
      genes required for oxidative conversion of cyclododecanone to 1,12-dodecanedioic
      acid (DDDA). The genes required for cyclododecanone oxidation were only
      marginally similar to the analogous genes for cyclohexanone oxidation. The
      biochemical function of the enzymes encoded on the 10-kb gene cluster, the flavin
      monooxygenase, the lactone hydrolase, the alcohol dehydrogenase, and the aldehyde
      dehydrogenase, was determined in Escherichia coli based on the ability to convert
      cyclododecanone. Recombinant E. coli strains grown in the presence of
      cyclododecanone accumulated lauryl lactone, 12-hydroxylauric acid, and/or DDDA
      depending on the genes cloned. The cyclododecanone monooxygenase is a type 1
      Baeyer-Villiger flavin monooxygenase (FAD as cofactor) and exhibited substrate
      specificity towards long-chain cyclic ketones (C11 to C15), which is different
      from the specificity of cyclohexanone monooxygenase favoring short-chain cyclic
      compounds (C5 to C7).

PMID- 11591692
TI  - Acetate and formate stress: opposite responses in the proteome of Escherichia
      coli.
AB  - Acetate and formate are major fermentation products of Escherichia coli. Below pH
      7, the balance shifts to lactate; an oversupply of acetate or formate retards
      growth. E. coli W3110 was grown with aeration in potassium-modified Luria broth
      buffered at pH 6.7 in the presence or absence of added acetate or formate, and
      the protein profiles were compared by two-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Acetate increased the steady-state expression
      levels of 37 proteins, including periplasmic transporters for amino acids and
      peptides (ArtI, FliY, OppA, and ProX), metabolic enzymes (YfiD and GatY), the
      RpoS growth phase regulon, and the autoinducer synthesis protein LuxS. Acetate
      repressed 17 proteins, among them phosphotransferase (Pta). An ackA-pta deletion,
      which nearly eliminates interconversion between acetate and acetyl-coenzyme A
      (acetyl-CoA), led to elevated basal levels of 16 of the acetate-inducible
      proteins, including the RpoS regulon. Consistent with RpoS activation, the ackA
      pta strain also showed constitutive extreme-acid resistance. Formate, however,
      repressed 10 of the acetate-inducible proteins, including the RpoS regulon. Ten
      of the proteins with elevated basal levels in the ackA-pta strain were repressed
      by growth of the mutant with formate; thus, the formate response took precedence
      over the loss of the ackA-pta pathway. The similar effects of exogenous acetate
      and the ackA-pta deletion, and the opposite effect of formate, could have several
      causes; one possibility is that the excess buildup of acetyl-CoA upregulates
      stress proteins but excess formate depletes acetyl-CoA and downregulates these
      proteins.

PMID- 11591694
TI  - Interaction of MutS and Vsr: some dominant-negative mutS mutations that disable
      methyladenine-directed mismatch repair are active in very-short-patch repair.
AB  - In Escherichia coli and related bacteria, the very-short-patch (VSP) repair
      pathway uses an endonuclease, Vsr, to correct T-G mismatches that result from the
      deamination of 5-methylcytosines in DNA to C-G. The products of mutS and mutL,
      which are required for adenine methylation-directed mismatch repair (MMR),
      enhance VSP repair. Multicopy plasmids carrying mutS alleles that are dominant
      negative for MMR were tested for their effects on VSP repair. Some mutS mutations
      (class I) did not lower VSP repair in a mutS(+) background, and most class I
      mutations increased VSP repair in mutS cells more than plasmids containing
      mutS(+). Other plasmid-borne mutS mutations (class II) and mutS(+) decreased VSP
      repair in the mutS(+) background. Thus, MutS protein lacking functions required
      for MMR can still participate in VSP repair, and our results are consistent with
      a model in which MutS binds transiently to the mispair and then translocates away
      from the mispair to create a specialized structure that enhances the binding of
      Vsr.

PMID- 11591695
TI  - Transcription-induced cytosine-to-thymine mutations are not dependent on sequence
      context of the target cytosine.
AB  - We showed previously that transcription of a plasmid-borne kan allele increases C
      to-T mutations in the nontranscribed strand. Using two new plasmid-borne kan
      alleles, one cmp allele, and a chromosomal kan allele, we found in this study
      that transcription-induced mutations are not limited to specific genes, alleles,
      or locations and are likely to be a general property of transcript elongation in
      Escherichia coli.

PMID- 11591696
TI  - Killing effect and antitoxic activity of the Leptospira interrogans toxin
      antitoxin system in Escherichia coli.
AB  - We report the first evidence of a chromosome-encoded toxin-antitoxin locus in
      spirochetes. This locus has been found in the pathogenic spirochete Leptospira
      interrogans and exhibits homologies with the pem/chp loci. The L. interrogans chp
      locus consists of two genes: chpK (for "killer protein") and its upstream partner
      chpI (for "inhibitory protein"). Expression of ChpK in Escherichia coli results
      in the inhibition of bacterial growth. The coexpression of ChpI neutralizes ChpK
      toxicity. By Southern blot analysis, chp homologs were found in all
      representative pathogenic strains of L. interrogans.

PMID- 11591697
TI  - A role for NF-kappa B in the induction of beta-R1 by interferon-beta.
AB  - Previous experiments have suggested that induction of the beta-R1 gene by
      interferon (IFN)-beta required transcription factor ISGF-3 (IFN-stimulated gene
      factor-3) and an additional component. We now provide evidence that nuclear
      factor-kappaB (NF-kappaB) can serve as this component. Site-directed mutagenesis
      of an NF-kappaB binding site in the beta-R1 promoter or over-expression of an
      IkappaBalpha super-repressor abrogated IFN-beta-mediated induction of a beta-R1
      promoter-reporter. IFN-beta treatment did not augment abundance of NF-kappaB but
      did lead to phosphorylation of the p65 NF-kappaB subunit. It is proposed that IFN
      beta-mediated enhancement of the transactivation competence of NF-kappaB
      components is required for inducible transcription of the beta-R1 promoter. These
      results provide a novel insight into the role of NF-kappaB in the transcriptional
      response to IFN-beta.

PMID- 11591698
TI  - Amino acid sequence determinants of extended spectrum cephalosporin hydrolysis by
      the class C P99 beta-lactamase.
AB  - Class C beta-lactamases are commonly encoded on the chromosome of Gram-negative
      bacterial species. Mutations leading to increased expression of these enzymes are
      a common cause of resistance to many cephalosporins including extended spectrum
      cephalosporins. Recent reports of plasmid- and integrin-encoded class C beta
      lactamases are a cause for concern because these enzymes are likely to spread
      horizontally to susceptible strains. Because of their increasing clinical
      significance, it is critical to identify the determinants of catalysis and
      substrate specificity of these enzymes. For this purpose, the codons of a set of
      21 amino acid residues that encompass the active site region of the P99 beta
      lactamase were individually randomized to create libraries containing all
      possible amino acid substitutions. The amino acid sequence requirements for the
      hydrolysis of ceftazidime, an extended spectrum cephalosporin commonly used to
      treat serious infections, were determined by selecting resistant mutants from
      each of the 21 libraries. DNA sequencing identified the residue positions that
      are critical for ceftazidime hydrolysis. In addition, it was found that certain
      amino acid substitutions in the omega-loop region of the P99 enzyme result in
      increased ceftazidime hydrolysis suggesting the loop is an important determinant
      of substrate specificity.

PMID- 11591699
TI  - Negative response elements in keratin genes mediate transcriptional repression
      and the cross-talk among nuclear receptors.
AB  - Very little is known about the mechanisms responsible for the findings that
      binding of nuclear receptors (NR) to some promoter elements leads to
      transcriptional activation, whereas binding to others leads to repression. Case
      in point is the group of epidermal keratin genes and their DNA sequences
      responsible for repression by NR. Keratin response elements (KREs) interact with
      receptors for retinoic acid, thyroid hormone, and glucocorticoids. KREs, by their
      structure and sequence, direct the binding of retinoic acid and thyroid hormone
      as homodimers and glucocorticoids as monomers. Such specific DNA-receptor
      interactions are crucial for the repression signal of transcription. In this
      paper we have analyzed the interactions between the KREs and NR that lead to such
      repression. We have found that KREs are promoter-independent. They not only
      provide a docking platform for the receptors, but also play a key role in
      directing the receptors to bind into particular configurations and coordinating
      the interactions among different receptors. Both an intact KRE and an intact
      receptor DNA-binding domain are necessary for the regulation to occur, which
      emphasizes the importance of interaction between the DNA and NR for proper
      signaling. Furthermore, KREs allow simultaneous binding of multiple receptors,
      thus providing fine-tuning of transcriptional regulation. The DNA/DNA-binding
      domain interactions in keratin promoters exemplify tissue and gene specificity of
      hormone action.

PMID- 11591700
TI  - Tip60 is a co-activator specific for class I nuclear hormone receptors.
AB  - The nuclear hormone receptor superfamily is composed of a group of hormone
      dependent transcription factors that play prominent roles in homeostatic events
      in vertebrates. A prerequisite for steroid hormone receptor activity is the
      binding of co-activator molecules to the activation function-2 domain of the
      receptor. The LXXLL motif/nuclear receptor box, contained within a number of co
      activator molecules, mediates the interaction with nuclear hormone receptors.
      Tip60 (Tat-interactive protein 60 kDa), previously shown to bind to and enhance
      androgen receptor (AR)-mediated transactivation, contains a single nuclear
      receptor box at its extreme C terminus. We demonstrate that unlike members of the
      p160 co-activator family that interact predominantly with the N terminus of the
      AR in an LXXLL motif-independent manner, the LXXLL motif of Tip60 is required and
      is sufficient for AR interaction. Furthermore, by using the mammalian two-hybrid
      system and transient transfection experiments, we show that Tip60 preferentially
      interacts with and up-regulates class I nuclear receptors, suggesting that Tip60
      is a steroid hormone receptor-specific co-activator. We conclude that Tip60 may
      specifically regulate a subset of nuclear hormone receptors, giving an indication
      to how regulated nuclear receptor activation can be achieved.

PMID- 11591701
TI  - Modulation of COX-2 expression by statins in human aortic smooth muscle cells.
      Involvement of geranylgeranylated proteins.
AB  - Cyclooxygenase (COX)-2 and COX-1 play an important role in prostacyclin
      production in vessels and participate in maintaining vascular homeostasis.
      Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)
      reductase, which is crucial in cholesterol biosynthesis. Recently, cholesterol
      independent effects of statins have been described. In this study, we evaluated
      the effect of two inhibitors of HMG CoA reductase, mevastatin and lovastatin, on
      the production of prostacyclin and the expression of COX in human aortic smooth
      muscle cells. Treatment of cells with 25 microm mevastatin or lovastatin resulted
      in the induction of COX-2 and increase in prostacyclin production. Mevalonate,
      the direct metabolite of HMG CoA reductase, and geranylgeranyl-pyrophosphate
      reversed this effect. GGTI-286, a selective inhibitor of
      geranylgeranyltransferases, increased COX-2 expression and prostacyclin
      formation, thus indicating the involvement of geranylgeranylated proteins in the
      down-regulation of COX-2. Furthermore, Clostridium difficile toxin B, an
      inhibitor of the Rho GTP-binding protein family, the Rho selective inhibitor C3
      transferase, and Y-27632, a selective inhibitor of the Rho-associated kinases,
      targets of Rho A, increased COX-2 expression whereas the activator of the Rho
      GTPase, the cytotoxic necrotizing factor 1, blocked interlukin-1alpha-dependent
      COX-2 induction. These results demonstrate that statins up-regulate COX-2
      expression and subsequent prostacyclin formation in human aortic smooth muscle
      cells in part through inhibition of Rho.

PMID- 11591702
TI  - A factor of inducing IgE from a filarial parasite is an agonist of human CD40.
AB  - Immune responses to parasitic helminth are usually characterized by quite
      mysterious phenomena: dominance of Th2-like immunity and antigen-nonspecific IgE
      secretion. We previously purified a factor from Dirofilaria immitis that induces
      antigen-nonspecific IgE in rats and named it DiAg. In the presence of IL-4, DiAg
      induces mouse B cells to secrete IgE, which is antigen-nonspecific polyclonal
      antibody. We investigated the biochemical characteristics of DiAg as a factor of
      inducing IgE in this study. Recombinant DiAg (rDiAg) with interleukin (IL)-4
      induced IgE synthesis in highly purified human normal B cells in vitro cell
      culture systems. The addition of recombinant human soluble CD40 IgG fusion
      protein (rsCD40-Ig) inhibited induction of IgE synthesis by rDiAg with IL-4.
      Monocyte cells were stimulated with rDiAg and recombinant human soluble CD40L
      (rsCD40L); IL-12 and TNF-alpha were induced. The addition of rsCD40-Ig to THP-1
      cells activated with rDiAg and rsCD40L inhibited the production of IL-12. rDiAg
      bound to the monocyte cell membrane fraction and recombinant human soluble CD40;
      this binding of rDiAg was competitively inhibited by addition of rsCD40L.
      Moreover, in CD40-deficient mice, IgE production and MLN-B cell proliferation by
      rDiAg were completely absent. Based on these results, we concluded that DiAg is
      an agonist of CD40.

PMID- 11591703
TI  - Base excision repair intermediates as topoisomerase II poisons.
AB  - Abasic sites are the most commonly formed DNA lesions in the cell and are
      produced by numerous endogenous and environmental insults. In addition, they are
      generated by the initial step of base excision repair (BER). When located within
      a topoisomerase II DNA cleavage site, "intact" abasic sites act as topoisomerase
      II poisons and dramatically stimulate enzyme-mediated DNA scission. However, most
      abasic sites in cells are not intact. They exist as processed BER intermediates
      that contain DNA strand breaks proximal to the damaged residue. When strand
      breaks are located within a topoisomerase II DNA cleavage site, they create
      suicide substrates that are not religated readily by the enzyme and can generate
      permanent double-stranded DNA breaks. Consequently, the effects of processed
      abasic sites on DNA cleavage by human topoisomerase IIalpha were examined. Unlike
      substrates with intact abasic sites, model BER intermediates containing 5'- or 3'
      nicked abasic sites or deoxyribosephosphate flaps were suicide substrates.
      Furthermore, abasic sites flanked by 5'- or 3'-nicks were potent topoisomerase II
      poisons, enhancing DNA scission approximately 10-fold compared with corresponding
      nicked oligonucleotides that lacked abasic sites. These findings suggest that
      topoisomerase II is able to convert processed BER intermediates to permanent
      double-stranded DNA breaks.

PMID- 11591704
TI  - differential L-selectin binding activities of human hematopoietic cell L-selectin
      ligands, HCELL and PSGL-1.
AB  - Expression of L-selectin on human hematopoietic cells (HC) is associated with a
      higher proliferative activity and a more rapid engraftment after hematopoietic
      stem cell transplantation. Two L-selectin ligands are expressed on human HCs, P
      selectin glycoprotein ligand-1 (PSGL-1) and a specialized glycoform of CD44
      (hematopoietic cell E- and L-selectin ligand, HCELL). Although the structural
      biochemistry of HCELL and PSGL-1 is well characterized, the relative capacity of
      these molecules to mediate L-selectin-dependent adhesion has not been explored.
      In this study, we examined under shear stress conditions L-selectin-dependent
      leukocyte adhesive interactions mediated by HCELL and PSGL-1, both as naturally
      expressed on human HC membranes and as purified molecules. By utilizing both
      Stamper-Woodruff and parallel-plate flow chamber assays, we found that HCELL
      displayed a 5-fold greater capacity to support L-selectin-dependent leukocyte
      adherence across a broad range of shear stresses compared with that of PSGL-1.
      Moreover, L-selectin-mediated leukocyte binding to immunopurified HCELL was
      consistently >5-fold higher than leukocyte binding to equivalent amounts of PSGL
      1. Taken together, these data indicate that HCELL is a more avid L-selectin
      ligand than PSGL-1 and may be the preferential mediator of L-selectin-dependent
      adhesive interactions among human HCs in the bone marrow.

PMID- 11591705
TI  - Protein phosphatase 2A interacts with and directly dephosphorylates RelA.
AB  - Nuclear factor-kappa B (NF-kappa B)/Rel transcription factors are key regulators
      of a variety of genes involved in inflammatory responses, growth,
      differentiation, apoptosis, and development. There are increasing lines of
      evidence that NF-kappa B/Rel activity is controlled to a great extent by its
      phosphorylation state. In this study, we demonstrated that RelA physically
      associated with protein phosphatase 2A (PP2A) subunit A (PR65). Both the N- and C
      terminal regions of RelA were responsible for the PP2A binding. RelA co
      immunoprecipitated with PP2A in melanocytes in the absence of stimulation,
      indicating that RelA forms a signaling complex with PP2A in the cells. RelA was
      dephosphorylated by a purified PP2A core enzyme, a heterodimer formed by the
      catalytic subunit of PP2A (PP2Ac) and PR65, in a concentration-dependent manner.
      Okadaic acid, an inhibitor of PP2A at lower concentration, increased the basal
      phosphorylation of RelA in melanocytes and blocked the dephosphorylation of RelA
      after interleukin-1 stimulation. Interestingly, PP2A immunoprecipitated from
      melanocytes was able to dephosphorylate RelA, whereas PP2A immunoprecipitated
      from melanoma cell lines exhibited decreased capacity to dephosphorylate RelA in
      vitro. Moreover, in melanoma cells in which I kappa B kinase activity was
      inhibited by sulindac to a similar level as in melanocytes, the phosphorylation
      state of RelA and the relative NF-kappa B activity were still higher than those
      in normal melanocytes. These data suggest that the constitutive activation of
      RelA in melanoma cells (Yang, J., and Richmond, A. (2001) Cancer Res. 61, 4901
      4909) could be due, at least in part, to the deficiency of PP2A, which exhibits
      decreased dephosphorylation of NF-kappa B/RelA.

PMID- 11591706
TI  - Double prenylation by RabGGTase can proceed without dissociation of the mono
      prenylated intermediate.
AB  - Rab geranylgeranyltransferase (RabGGTase) catalyzes the prenylation of Rab
      proteins. Despite possessing a single active site, RabGGTase is able to add
      geranylgeranyl moieties onto each of the two C-terminal cysteine residues of Rab.
      We have studied the kinetics of Rab double prenylation employing a combination of
      a novel high pressure liquid chromatography (HPLC)-based in vitro prenylation
      assay and fluorescence spectroscopy. Transfer of the first geranylgeranyl group
      proceeds with a k(1) = 0.16 s(-1), while the conversion from singly to double
      prenylated Rab is 4-fold slower (k(2) = 0.039 s(-1)). We found that following the
      first transfer reaction, the conjugated lipid is removed from the active site of
      RabGGTase but mono-prenylated Rab.REP complex remains bound to RabGGTase with a
      K(d) < 1 nm. In contrast to the doubly prenylated Rab7.REP dissociation of the
      mono-prenylated species from RabGGTase was only weakly stimulated by
      phosphoisoprenoid. Based on the obtained rate constants we calculated that at
      least 72% of mono-prenylated Rab molecules proceed to double prenylation without
      dissociating from RabGGTase. The obtained data provides an explanation of how
      RabGGTase discriminates between mono-prenylated intermediate and double
      prenylated reaction product. It also indicates that the phosphoisoprenoid acts
      both as a substrate and as a sensor governing the kinetics of protein.protein
      interactions in the double prenylation reaction.

PMID- 11591707
TI  - An early growth response protein (Egr) 1 cis-element is required for gonadotropin
      releasing hormone-induced mitogen-activated protein kinase phosphatase 2 gene
      expression.
AB  - In pituitary gonadotropes, gonadotropin-releasing hormone (GnRH) activates all
      three major mitogen-activated protein kinase (MAPK) cascades. The MAPKs play key
      roles in transcriptional activation of GnRH-responsive genes. MAPK phosphatases
      (MKPs) are dual specificity protein phosphatases involved in feedback regulation
      of MAPK activity. Previous studies indicate that GnRH activates MKP-2 expression
      in gonadotropes, dependent upon activation of multiple MAPKs and discrete Ca(2+)
      signals. To further understand the transcriptional mechanism(s) of MKP-2
      induction by GnRH, we studied the activity of a 198-nucleotide MKP-2 proximal
      promoter region that supports GnRH responsiveness in reporter gene assays.
      Functional analysis of the MKP-2 promoter confirmed a requirement for the protein
      kinase C-extracellular signal-regulated kinase (ERK) pathway and VGCC-derived
      Ca(2+) signals in transcriptional activation of the MKP-2 gene. However, the
      inhibitory effect of thapsigargin on MKP-2 protein expression previously
      identified was not mediated at the level of promoter activation, suggesting a
      distinct mechanism for the action of thapsigargin-sensitive Ca(2+) signals. MGRE
      (MKP-2 GnRH response element) within the MKP-2 promoter mediated promoter
      activation through the protein kinase C-ERK pathway. The zinc finger
      transcription factor Egr-1 was identified in the MGRE-binding complex. Egr-1/MGRE
      binding was induced by GnRH in an ERK-dependent manner. Transcriptional activity
      of Egr-1 protein was enhanced by GnRH treatment. In addition, overexpression of
      the Egr-interacting protein, NAB1, resulted in increased GnRH-stimulated MKP-2
      gene transcription. Consistent with the putative role of Egr-1 in MKP-2 promoter
      regulation, Egr-1 protein expression closely correlated with the expression of
      MKP-2 protein in alpha T3-1 cells. Together, these data suggest that Egr-1 may be
      a key factor in mediating GnRH-dependent transcriptional activation of the MKP-2
      gene.

PMID- 11591708
TI  - Identification and characterization of a novel member of the heterodimeric amino
      acid transporter family presumed to be associated with an unknown heavy chain.
AB  - We identified a novel amino acid transporter designated Asc-2 (for asc-type amino
      acid transporter 2). Asc-2 exhibited relatively low but significant sequence
      similarity to the members of the heterodimeric amino acid transporters. The
      cysteine residue responsible for the disulfide bond formation between
      transporters (light chains) and heavy chain subunits in the heterodimeric amino
      acid transporters is conserved for Asc-2. Asc-2 is, however, not colocalized with
      the already known heavy chains such as 4F2 heavy chain (4F2hc) or related to
      b(0,+) amino acid transporter (rBAT) in mouse kidney. Because Asc-2 solely
      expressed or coexpressed with 4F2hc or rBAT did not induce functional activity,
      we generated fusion proteins in which Asc-2 is connected with 4F2hc or rBAT. The
      fusion proteins were sorted to the plasma membrane and expressed the function
      corresponding to the Na(+)-independent small neutral amino acid transport system
      asc. Distinct from the already identified system asc transporter Asc-1 which is
      associated with 4F2hc, Asc-2-mediated transport is less stereoselective and did
      not accept some of the high affinity substrates of Asc-1 such as alpha
      aminoisobutyric acid and beta-alanine. Asc-2 message was detected in kidney,
      placenta, spleen, lung, and skeletal muscle. In kidney, Asc-2 protein was present
      in the epithelial cells lining collecting ducts. In the Western blot analysis on
      mouse erythrocytes and kidney, Asc-2 was detected as multiple bands in the
      nonreducing condition, whereas the bands shifted to a single band at lower
      molecular weight, suggesting the association of Asc-2 with other protein(s) via a
      disulfide bond. The finding of Asc-2 would lead to the establishment of a new
      subgroup of heterodimeric amino acid transporter family which includes
      transporters associated not with 4F2hc or rBAT but with other unknown heavy
      chains.

PMID- 11591709
TI  - The murine cysteinyl leukotriene 2 (CysLT2) receptor. cDNA and genomic cloning,
      alternative splicing, and in vitro characterization.
AB  - Two classes of cysteinyl leukotriene receptor, CysLT(1) and CysLT(2), have been
      identified and pharmacologically characterized in human tissues. Although the
      CysLT(1) receptor mediates the proinflammatory effects of leukotrienes in human
      asthma, the physiological roles of CysLT(2) receptor are not defined, and a
      suitable mouse model would be useful in delineating function. We report here the
      molecular cloning and characterization of the mouse CysLT(2) receptor
      (mCysLT(2)R) from heart tissue. mCysLT(2)R cDNA encodes a protein of 309 amino
      acids, truncated at both ends compared with the human ortholog (hCysLT(2)R). The
      gene resides on the central region of mouse chromosome 14 and is composed of 6
      exons with the entire coding region located in the last exon. Two 5'-untranslated
      region splice variants were identified with the short form lacking exon 3 as the
      predominant transcript. Although the overall expression of mCysLT(2)R is very
      low, the highest expression was detected in spleen, thymus, and adrenal gland by
      ribonuclease protection assay, and discrete sites of expression in heart were
      observed by in situ hybridization. Intracellular calcium mobilization in response
      to cysteinyl leukotriene administration was detected in human embryonic kidney
      293T cells transfected with recombinant mCysLT(2)R with a rank order of potency
      leukotriene C(4)(LTC(4) ) = LTD(4)>>LTE(4). [(3)H]LTD(4) binding to membranes
      expressing mCysLT(2)R could be effectively competed by LTC(4) and LTD(4) and only
      partially inhibited by LTE(4) and BAYu9773. The identification of mCysLT(2)R will
      be useful for establishing CysLT(2)R-deficient mice and determining novel
      leukotriene functions.

PMID- 11591710
TI  - High pressure refolding of recombinant human growth hormone from insoluble
      aggregates. Structural transformations, kinetic barriers, and energetics.
AB  - Two different types of insoluble, non-native aggregates of recombinant human
      growth hormone were formed by agitation in buffer or buffer containing 0.75 m
      guanidine HCl (GdnHCl) and characterized by infrared and second derivative UV
      spectroscopies. The degree of secondary structural perturbation was greater in
      the aggregates formed in 0.75 m GdnHCl. Both aggregate types were dissolved and
      refolded using high hydrostatic pressures in combination with either elevated
      temperature or non-denaturing levels of guanidine HCl or urea. The effects of a
      range of temperature, pressure, and chaotrope concentrations were tested and led
      to optimal conditions that approached 100% yield of native protein. The
      aggregates formed in 0.75 m GdnHCl required higher concentrations of urea or
      GdnHCl, or higher temperature or pressure for a yield equivalent to that for
      aggregates formed in buffer alone. Investigation of the effects of pressure,
      temperature, and chaotrope on unfolding of rhGH documented that under conditions
      used for optimal high pressure disaggregation and refolding, the native state is
      greatly favored thermodynamically (e.g. 25 kJ/mol at 2000 bar and 0.75 m GdnHCl).
      Dissolution of aggregates under pressure is a kinetically limited process.
      Comparison of refolding yields in GdnHCl and urea solutions suggest that pressure
      effects on electrostatic interactions do not dominate pressure effects on
      disaggregation. We suggest that non-native hydrogen bonds between protein
      molecules within aggregates of recombinant human growth hormone are responsible
      for the rate-limiting kinetic barrier in pressure-induced disaggregation.

PMID- 11591711
TI  - Constitutive activation of extracellular signal-regulated kinase 2 by synergistic
      point mutations.
AB  - Constitutively active mutant forms of signaling enzymes provide insight into
      mechanisms of activation as well as useful molecular tools for probing downstream
      targets. In this study, point mutations in ERK2 at conserved residues L73P and
      S151D were identified that individually led to 8-12-fold increased specific
      activity and in combination reached 50-fold, indicating synergistic interactions
      between these residues. Examination by mass spectrometry, phosphatase
      sensitivity, and Western blotting revealed that the mutations enhanced ERK2
      activity by facilitating intramolecular autophosphorylation predominantly at Tyr
      185 and to a lesser extent at Thr-183 and that phosphorylation at both sites is
      required for activation. A set of short molecular dynamics simulations were
      carried out using different random seeds to sample locally accessible
      configurations. Simulations of the active mutant showed potential hydrogen
      bonding interactions between the phosphoryl acceptor and catalytic nucleophile,
      which could account for enhanced intramolecular autophosphorylation. In intact
      cells, the ERK2 mutants were functionally active in phosphorylating Elk-1 and
      RSK1 and activating the c-fos promoter. This activity was only partially reduced
      upon treatment of cells with the MKK1/2 inhibitor, U0126, indicating that in vivo
      the mechanism of ERK2 activation occurs substantially through autophosphorylation
      and partially through phosphorylation by MKK1/2.

PMID- 11591712
TI  - Nuclear export of mammalian PERIOD proteins.
AB  - The timing of mammalian circadian rhythm is determined by interlocking negative
      and positive transcriptional feedback loops that govern the cyclic expression of
      both clock regulators and output genes. In mammals, nuclear localization of the
      circadian regulators PER1-3 is controlled by multiple mechanisms, including
      multimerization with PER and CRY proteins. In addition, nuclear entry of
      mammalian PER1 (mPER1) can be regulated by a phosphorylation-dependent masking of
      its nuclear localization signal. Here we present evidence suggesting that nuclear
      localization of PER proteins is a dynamic process determined by both nuclear
      import and previously unrecognized nuclear export pathways. Examination of the
      subcellular localization of a series of truncated mPER1 proteins demonstrated
      that cytoplasmic localization is mediated by an 11-amino acid region with
      homology to leucine-rich nuclear export signals (NESs). Similar sequences were
      identified in mPER2 and mPER3 as well as in several insect PER proteins. The
      putative NESs from mPER1 and mPER2 were able to direct cytoplasmic accumulation
      when fused to a heterologous protein. Mutations in conserved NES residues and the
      nuclear export inhibitor leptomycin B each blocked the function of the NES. Full
      length mPER1 was also exported from microinjected Xenopus laevis oocyte nuclei in
      an NES-dependent manner. The presence of a functional NES in mPER1 and mPER2 as
      well as related sequences in a variety of other PER proteins suggests that
      nuclear export may be a conserved and important feature of circadian regulators.

PMID- 11591713
TI  - Dual role of p300 in the regulation of p53 stability.
AB  - While the function of p300 as a transcriptional co-activator of p53 is well
      documented, its role in the regulation of p53 stability remains ill-defined since
      opposite effects of p300 on p53 levels have been reported. We show here that p300
      stabilizes both p53 and its negative regulator MDM2, thereby enhancing the
      p53/MDM2 negative regulatory loop. Binding of p300 is associated with the
      retention of p53 in the nucleus, which results in the accumulation of p53 in an
      acetylase-independent manner. Stabilization of MDM2, on the other hand, requires
      the acetylase activity of p300. Importantly, MDM2, once expressed, is able to
      reverse the stabilizing effect of p300 on p53. A temperature-permissive p53
      expressing cell line enabled us to demonstrate the completely opposite roles of
      p300 in the regulation of p53 stability, depending on the expression of MDM2.
      Prior to p53 activation, when MDM2 levels are low, p300 acts as a positive
      regulator to increase p53 levels. Upon shifting to permissive temperature,
      however, when MDM2 expression is induced, p300 becomes a negative regulator of
      p53 by stabilizing MDM2 and thereby augmenting MDM2's ability to target p53 for
      degradation.

PMID- 11591714
TI  - Inhibitory mechanisms of tea polyphenols on the ultraviolet B-activated
      phosphatidylinositol 3-kinase-dependent pathway.
AB  - In this study, we investigated the effect of tea polyphenols, (-)
      epigallocatechin-3-gallate or theaflavins, on UVB-induced phosphatidylinositol 3
      kinase (PI3K) activation in mouse epidermal JB6 Cl 41 cells. Pretreatment of
      cells with these polyphenols inhibited UVB-induced PI3K activation. Furthermore,
      UVB-induced activation of Akt and ribosomal p70 S6 kinase (p70 S6-K), PI3K
      downstream effectors, were also attenuated by the polyphenols. In addition to
      LY294002, a PI3K inhibitor, pretreatment with a specific mitogen-activated
      protein/extracellular signal-regulated protein kinases (Erks) kinase 1 inhibitor,
      U0126, or a specific p38 kinase inhibitor, SB202190, blocked UVB-induced
      activation of both Akt and p70 S6-K. Pretreatment with LY294002 restrained UVB
      induced phosphorylation of Erks, suggesting that in UVB signaling, the Erk
      pathway is mediated by PI3K. Moreover, pretreatment with rapamycin, an inhibitor
      of p70 S6-K, inhibited UVB-induced activation of p70 S6-K, but UVB-induced
      activation of Akt did not change. Interestingly, UVB-induced p70 S6-K activation
      was directly blocked by the addition of (-)-epigallocatechin-3-gallate or
      theaflavins, whereas these polyphenols showed only a weak inhibition on UVB
      induced Akt activation. Because PI3K is an important factor in carcinogenesis,
      the inhibitory effect of these polyphenols on activation of PI3K and its
      downstream effects may further explain the anti-tumor promotion action of these
      tea constituents.

PMID- 11591715
TI  - Stimulation of interleukin-8 production in human THP-1 macrophages by
      apolipoprotein(a). Evidence for a critical involvement of elements in its C
      terminal domain.
AB  - In the vessel wall, macrophages are among the cells that upon activation
      contribute to the atherosclerotic process. Low density lipoproteins (LDL) can
      mediate this activation but only after enzymatic or oxidative modification.
      Lipoprotein(a) (Lp(a)) is an LDL variant that has been shown to have an
      atherogenic potential by no clearly established mechanisms. In the present study
      we examined whether native Lp(a) can activate macrophages and, if so, identify
      the structural elements involved in this action. For this purpose, we utilized
      human THP-1 macrophages, prepared by treating THP-1 monocytes with phorbol ester,
      and we exposed them to Lp(a) and its two derivatives, apo(a)-free LDL (Lp(a-))
      and free apo(a). We also studied apo(a) fragments, F1 (N terminus) and F2 (C
      terminus) and subfragments thereof, obtained by leukocyte elastase digestion. By
      Northern blot analyses, Lp(a), but not Lp(a-), caused up to a 12-fold increase in
      interleukin 8 (IL-8) mRNA as compared with untreated cells. Free apo(a) also
      induced the production of IL-8 mRNA; however, the effect was 3-4-fold higher than
      that of Lp(a). The increase in mRNA was associated with the accumulation of IL-8
      protein in the culture medium. F1 had only a minimal effect, whereas F2 was 1.5-2
      fold more potent than apo(a), an activity mostly contained in the Kringle V
      protease region. A monoclonal antibody specific for Kringle V inhibited the
      apo(a)-mediated effect on IL-8. We conclude that Lp(a) via elements contained in
      the C-terminal domain of apo(a) causes in THP-1 macrophages an increased
      production of IL-8, a chemokine with pro-inflammatory properties, an event that
      may be relevant to the process of atherosclerosis.

PMID- 11591716
TI  - Poxvirus infection rapidly activates tyrosine kinase signal transduction.
AB  - Viruses have evolved a number of strategies to gain entry and replicate in host
      target cells that, for human immunodeficiency virus (HIV) and the poxvirus,
      myxoma virus, involve appropriating chemokine receptors. In this report we
      demonstrate that activation of multiple intracellular tyrosine phosphorylation
      events rapidly ensues following virus adsorption to NIH 3T3.CD4.CCR5 cells and
      affects the ultimate level of myxoma virus replication. UV-inactivated myxoma
      virus induces the rapid phosphorylation of CCR5 on tyrosine residues, the
      association of CCR5 with Jaks and p56(lck), and their phosphorylation-activation
      within minutes of virus adsorption. Additionally, we provide evidence for myxoma
      virus-inducible signal transducers and activators of transcription (Stat) and
      insulin receptor substrate (IRS) activation. In contrast to CCR5 activation
      effected by HIV Env protein, these myxoma virus-inducible phosphorylation events
      are not sensitive to pertussis toxin treatment. Moreover, in cells that are non
      permissive for myxoma virus infection, we provide evidence that myxoma virus
      fails to invoke this tyrosine phosphorylation cascade. Consistent with the
      observation that infection of CCR5-expressing cells is blocked by herbimycin A
      and the Jak 2 inhibitor, tyrophostin AG490, we infer that viral infectivity may
      be dependent on non-G-protein-coupled signal transduction pathways triggered by
      the infecting myxoma virus particle. This provides a novel post-binding mechanism
      by which viruses can co-opt a cellular receptor to permit productive virus
      infection.

PMID- 11591717
TI  - Catabolism of pyrimidine nucleotides in the deep-sea tube worm Riftia pachyptila.
AB  - The present study describes the distribution and properties of enzymes of the
      catabolic pathway of pyrimidine nucleotides in Riftia pachyptila, a tubeworm
      living around deep-sea hydrothermal vents and known to be involved in a highly
      specialized symbiotic association with a bacterium. The catabolic enzymes, 5'
      nucleotidase, uridine phosphorylase, and uracil reductase, are present in all
      tissues of the worm, whereas none of these enzymatic activities were found in the
      symbiotic bacteria. The 5'-nucleotidase activity was particularly high in the
      trophosome, the symbiont-harboring tissue. These results suggest that the
      production of nucleosides in the trophosome may represent an alternative source
      of carbon and nitrogen for R. pachyptila, because these nucleosides can be
      delivered to other parts of the worm. This process would complement the source of
      carbon and nitrogen from organic metabolites provided by the bacterial
      assimilatory pathways. The localization of the enzymes participating in
      catabolism, 5'-nucleotidase and uridine phosphorylase, and of the enzymes
      involved in the biosynthesis of pyrimidine nucleotides, aspartate
      transcarbamylase and dihydroorotase, shows a non-homogeneous distribution of
      these enzymes in the trophosome. The catabolic enzymes 5'-nucleotidase and
      uridine phosphorylase activities increase from the center of the trophosome to
      its periphery. In contrast, the anabolic enzymes aspartate transcarbamylase and
      dihydroorotase activities decrease from the center toward the periphery of the
      trophosome. We propose a general scheme of anatomical and physiological
      organization of the metabolic pathways of the pyrimidine nucleotides in R.
      pachyptila and its bacterial endosymbiont.

PMID- 11591718
TI  - Intracellular localization of the Ret finger protein depends on a functional
      nuclear export signal and protein kinase C activation.
AB  - The Ret finger protein (RFP) was identified initially as an oncogene product and
      belongs to a family of proteins that contain a tripartite motif consisting of a
      RING finger, a B box, and a coiled-coil domain. RFP represses transcription by
      interacting with Enhancer of Polycomb and is localized to the cytoplasm or
      nucleus depending on the cell type. Here, we have identified the nuclear export
      signal (NES) located in the coiled-coil region of RFP. Mutation of this NES or
      treatment with leptomycin B abrogated the nuclear export of RFP in NIH3T3 cells.
      In addition, fusion of this NES to other nuclear proteins, such as yeast
      transcription factor Gal4, resulted in their release into the cytoplasm of NIH3T3
      cells. Although the NES function of RFP in HepG2 cells is masked by another
      domain in RFP or by another protein, 12-O-tetradecanoylphorbol-13-acetate
      treatment or overexpression of constitutively active protein kinase Calpha
      (PKCalpha) abrogated masking, leading to the cytoplasmic localization of RFP.
      Furthermore, treatment of NIH3T3 cells with PKC inhibitors blocked the function
      of NES, resulting in nuclear localization of RFP. Thus, the nuclear export of RFP
      is regulated positively by PKC activation. However, RFP was not a direct
      substrate of PKC, and additional signaling pathways may be involved in the
      regulation of nuclear export of RFP.

PMID- 11591719
TI  - In vitro characterization of a purified NS2/3 protease variant of hepatitis C
      virus.
AB  - The cleavage of the hepatitis C virus polyprotein between the nonstructural
      proteins NS2 and NS3 is mediated by the NS2/3 protease, whereas the NS3 protease
      is responsible for the cleavage of the downstream proteins. Purification and in
      vitro characterization of the NS2/3 protease has been hampered by its hydrophobic
      nature. NS2/3 protease activity could only be detected in cells or in in vitro
      translation assays with the addition of microsomal membranes or detergent. To
      facilitate purification of this poorly characterized protease, we truncated the N
      terminal hydrophobic domain, resulting in an active enzyme with improved
      biophysical properties. We define a minimal catalytic region of NS2/3 protease
      retaining autocleavage activity that spans residues 904-1206 and includes the C
      terminal half of NS2 and the N-terminal NS3 protease domain. The NS2/3 (904-1206)
      variant was purified from Escherichia coli inclusion bodies and refolded by gel
      filtration chromatography. The purified inactive form of NS2/3 (904-1206) was
      activated by the addition of glycerol and detergent to induce autocleavage at the
      predicted site between Leu(1026) and Ala(1027). NS2/3 (904-1206) activity was
      dependent on zinc ions and could be inhibited by NS4A peptides, peptides that
      span the cleavage site, or an N-terminal peptidic cleavage product. This NS2/3
      variant will facilitate the development of an assay suitable for identifying
      inhibitors of HCV replication.

PMID- 11591720
TI  - The involvement of HAb18G/CD147 in regulation of store-operated calcium entry and
      metastasis of human hepatoma cells.
AB  - The present study examined the effect of hepatoma-associated antigen HAb18G
      (homologous to CD147) expression on the NO/cGMP-regulated Ca(2+) mobilization and
      metastatic process of human hepatoma cells. HAb18G/CD147 cDNA was transfected
      into human 7721 hepatoma cells to obtain a cell line stably expressing
      HAb18G/CD147, T7721, as demonstrated by Northern blot and immunocytochemical
      studies. 8-Bromo-cGMP (cGMP) inhibited the thapsigargin-induced Ca(2+) entry in a
      concentration-dependent manner in 7721 cells. The cGMP-induced inhibition was
      abolished by an inhibitor of protein kinase G, KT5823 (1 microm). However,
      expression of HAb18G/CD147 in T7721 cells decreased the inhibitory response to
      cGMP. A similar concentration-dependent inhibitory effect on the Ca(2+) entry was
      observed in 7721 cells in response to a NO donor, (+/-)-S-nitroso-N
      acetylpenicillamine (SNAP). The inhibitory effect of SNAP on the thapsigargin
      induced Ca(2+) entry was significantly reduced in HAb18G/CD147-expressing T7721
      cells, indicating a role for HAb18G/CD147 in NO/cGMP-regulated Ca(2+) entry.
      Experiments investigating metastatic potentials demonstrated that HAb18G/CD147
      expressing T7721 cells attached to the Matrigel-coated culture plates and invaded
      through Matrigel-coated permeable filters at the rate significantly greater than
      that observed in 7721 cells. Both the attachment and invasion rates could be
      suppressed by SNAP, and the inhibitory effect of SNAP could be reversed by NO
      inhibitor, N(G)-nitro-l-arginine methyl ester. The sensitivity of the attachment
      and invasion rates to cGMP was significantly reduced in T7721 cells as compared
      with 7721 cells when cells were pretreated with thapsigargin. The difference in
      the sensitivity between the two cells could be abolished by a Ca(2+) channel
      blocker, Ni(2+) (3 mm). These results suggest that HAb18G/CD147 enhances
      metastatic potentials in human hepatoma cells by disrupting the regulation of
      store-operated Ca(2+) entry by NO/cGMP.

PMID- 11591721
TI  - The seven amino acids of human RAMP2 (86) and RAMP3 (59) are critical for agonist
      binding to human adrenomedullin receptors.
AB  - When co-expressed with a receptor activity-modifying protein (RAMP) accessory
      protein, calcitonin receptor-like receptor (CRLR) can function as a calcitonin
      gene-related peptide receptor (CRLR-RAMP1) or an adrenomedullin (AM) receptor
      (CRLR-RAMP2/3). Here we report on the structural domain(s) involved in selective
      AM binding that were examined using various RAMP chimeras and deletion mutants.
      Co-expression of chimeric RAMPs and CRLR in HEK293 cells revealed that residues
      77-101, situated in the extracellular N-terminal domain of human RAMP2 (hRAMP2),
      were crucial for selective AM-evoked cAMP production. More detailed analysis
      showed that deletion of hRAMP2 residues 86-92 significantly attenuated high
      affinity (125)I-AM binding and AM-evoked cAMP production despite full cell
      surface expression of the receptor heterodimer and that deletion of hRAMP3
      residues 59-65 had a similar effect. There is little sequence identity between
      hRAMP3 residues 59-65 and hRAMP2 residues 86-92; moreover, substituting alanine
      for Trp(86) (Ala(87)), Met(88), Ile(89), Ser(90), Arg(91), or Pro(92) of hRAMP2
      had no effect on AM-evoked cAMP production. It thus seems unlikely that any one
      amino acid residue is responsible for determining selective AM binding or that AM
      binds directly to these peptide segments. Instead these findings suggest that the
      respective seven-amino acid sequences confer selectivity either by directly
      contributing to the structure of ligand binding pocket or by allosteric
      modulation of the conformation of CRLR.

PMID- 11591722
TI  - Alternatively folded choriogonadotropin analogs. Implications for hormone folding
      and biological activity.
AB  - Most heterodimeric proteins are stabilized by intersubunit contacts or disulfide
      bonds. In contrast, human chorionic gonadotropin (hCG) and other glycoprotein
      hormones are secured by a strand of their beta-subunits that is wrapped around
      alpha-subunit loop 2 "like a seatbelt." During studies of hCG synthesis in COS-7
      cells, we found that, when the seatbelt was prevented from forming the disulfide
      that normally "latches" it to the beta-subunit, its carboxyl-terminal end can
      "scan" the surface of the heterodimer and become latched by a disulfide to
      cysteines substituted for residues in the alpha-subunit. Analogs in which the
      seatbelt was latched to residues 35, 37, 41-43, and 56 of alpha-subunit loop 2
      had similar lutropin activities to those of hCG; that in which it was latched to
      residue 92 at the carboxyl terminus had 10-20% the activity of hCG. Attachment of
      the seatbelt to alpha-subunit residues 45-51, 86, 88, 90, and 91 reduced lutropin
      activity substantially. These findings show that the heterodimer can form before
      the beta-subunit has folded completely and support the notions that the carboxyl
      terminal end of the seatbelt, portions of alpha-subunit loop 2, and the end of
      the alpha-subunit carboxyl terminus do not participate in lutropin receptor
      interactions. They suggest also that several different architectures could have
      been sampled without disrupting hormone activity as the glycoprotein hormones
      diverged from other cysteine knot proteins.

PMID- 11591723
TI  - Crystal structure of Klebsiella aerogenes UreE, a nickel-binding metallochaperone
      for urease activation.
AB  - UreE is proposed to be a metallochaperone that delivers nickel ions to urease
      during activation of this bacterial virulence factor. Wild-type Klebsiella
      aerogenes UreE binds approximately six nickel ions per homodimer, whereas
      H144*UreE (a functional C-terminal truncated variant) was previously reported to
      bind two. We determined the structure of H144*UreE by multi-wavelength anomalous
      diffraction and refined it to 1.5 A resolution. The present structure reveals an
      Hsp40-like peptide-binding domain, an Atx1-like metal-binding domain, and a
      flexible C terminus. Three metal-binding sites per dimer, defined by structural
      analysis of Cu-H144*UreE, are on the opposite face of the Atx1-like domain than
      observed in the copper metallochaperone. One metal bridges the two subunits via
      the pair of His-96 residues, whereas the other two sites involve metal
      coordination by His-110 and His-112 within each subunit. In contrast to the
      copper metallochaperone mechanism involving thiol ligand exchanges between
      structurally similar chaperones and target proteins, we propose that the Hsp40
      like module interacts with urease apoprotein and/or other urease accessory
      proteins, while the Atx1-like domain delivers histidyl-bound nickel to the urease
      active site.

PMID- 11591724
TI  - Vibrio vulnificus cytolysin induces superoxide anion-initiated apoptotic
      signaling pathway in human ECV304 cells.
AB  - Previous studies showed that exposure to Vibrio vulnificus cytolysin (VVC) caused
      characteristic morphologic changes and dysfunction of vascular structures in
      lung. VVC showed cytotoxicity for mammalian cells in culture and acted as a
      vascular permeability factor. In this study, the underlying mechanisms of VVC
      induced cytotoxicity was investigated on ECV304 cell, a human vascular
      endothelial cell line. When cells were exposed to 0.4 hemolytic units (HU) of
      VVC, consecutive apoptotic events were observed; the elevation of superoxide
      anion (O (-.)(2)), the release of cytochrome c, the activation of caspase-3, the
      cleavage of poly(ADP-ribose) polymerase, and the DNA fragmentation. The
      pretreatment with 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), O(-.)
      2) scavenger, completely abolished O(-.)(2) levels and downstream apoptotic
      events. Moreover, pretreatment with cyclosporin A (CsA), a mitochondrial
      permeability transition inhibitor, was capable of attenuating O(-.)(2)-mediated
      cytochrome c release and caspase-3 activation, and consequent apoptosis.
      Apoptosis, as demonstrated by oligonucleosomal DNA fragmentation and fluorescence
      microscopy, was induced 24 h after VVC treatment, which was also prevented by
      caspase-3 inhibitor, Ac-DEVD-CHO. Caspase-1 inhibitor, Ac-YVAD-CHO, did not
      protect ECV 304 cells from apoptosis. These results suggest a scenario where VVC
      induced apoptosis is triggered by the generation of O(-.)(2), release of
      cytochrome c from mitochondria, activation of caspase-3, degradation of poly(ADP
      ribose) polymerase, and DNA fragmentation. The induction of apoptosis in
      endothelial cells by VVC may provide a pivotal mechanism for understanding the
      pathophysiology of septicemia.

PMID- 11591725
TI  - Activation and deactivation kinetics of alpha 2A- and alpha 2C-adrenergic
      receptor-activated G protein-activated inwardly rectifying K+ channel currents.
AB  - Although G protein-coupled receptor-mediated signaling is one of the best studied
      biological events, little is known about the kinetics of these processes in
      intact cells. Experiments with neurons from alpha(2A)-adrenergic receptor
      knockout mice suggested that the alpha(2A)-receptor subtype inhibits
      neurotransmitter release with higher speed and at higher action potential
      frequencies than the alpha(2C)-adrenergic receptor. Here we investigated whether
      these functional differences between presynaptic alpha(2)-adrenergic receptor
      subtypes are the result of distinct signal transduction kinetics of these two
      receptors and their coupling to G proteins. alpha(2A)- and alpha(2C)-receptors
      were stably expressed in HEK293 cells at moderate ( approximately 2 pmol/mg) or
      high (17-24 pmol/mg) levels. Activation of G protein-activated inwardly
      rectifying K(+) (GIRK) channels was similar in extent and kinetics for alpha(2A)-
      and alpha(2C)-receptors at both expression levels. However, the two receptors
      differed significantly in their deactivation kinetics after removal of the
      agonist norepinephrine. alpha(2C)-Receptor-activated GIRK currents returned much
      more slowly to base line than did alpha(2A)-stimulated currents. This observation
      correlated with a higher affinity of norepinephrine at the murine alpha(2C)- than
      at the alpha(2A)-receptor subtype and may explain why alpha(2C)-adrenergic
      receptors are especially suited to control sympathetic neurotransmission at low
      action potential frequencies in contrast to the alpha(2A)-receptor subtype.

PMID- 11591726
TI  - Identification of sequences within the gamma-carboxylase that represent a novel
      contact site with vitamin K-dependent proteins and that are required for
      activity.
AB  - The vitamin K-dependent (VKD) carboxylase converts clusters of Glu residues to
      gamma-carboxylated Glu residues (Glas) in VKD proteins, which is required for
      their activity. VKD precursors are targeted to the carboxylase by their
      carboxylase recognition site, which in most cases is a propeptide. We have
      identified a second tethering site for carboxylase and VKD proteins that is
      required for carboxylase activity, called the vitamin K-dependent protein site of
      interaction (VKS). Several VKD proteins specifically bound an immobilized peptide
      comprising amino acids 343-355 of the human carboxylase (CVYKRSRGKSGQK) but not a
      scrambled peptide containing the same residues in a different order. Association
      with the 343-355 peptide was independent of propeptide binding, because the VKD
      proteins lacked the propeptide and because the 343-355 peptide did not disrupt
      association of a propeptide factor IX-carboxylase complex. Analysis with peptides
      that overlapped amino acids 343-355 indicated that the 343-345 CVY residues were
      necessary but not sufficient for prothrombin binding. Ionic interactions were
      also suggested because peptide-VKD protein binding could be disrupted by changes
      in ionic strength or pH. Mutagenesis of Cys(343) to Ser and Tyr(345) to Phe
      resulted in 7-11-fold decreases in vitamin K epoxidation and peptide (EEL)
      substrate and carboxylase carboxylation, and kinetic analysis showed 5-6-fold
      increases in K(m) values for the Glu substrate. These results suggest that
      Cys(343) and Tyr(345) are near the catalytic center and affect the active site
      conformation required for correct positioning of the Glu substrate. The 343-355
      VKS peptide had a higher affinity for carboxylated prothrombin (K(d) = 5 microm)
      than uncarboxylated prothrombin (K(d) = 60 microm), and the basic VKS region may
      also facilitate exiting of the Gla product from the catalytic center by ionic
      attraction. Tethering of VKD proteins to the carboxylase via the propeptide
      binding site and the VKS region has important implications for the mechanism of
      VKD protein carboxylation, and a model is proposed for how the carboxylase VKS
      region may be required for efficient and processive VKD protein carboxylation.

PMID- 11591727
TI  - Quantitation of the RNA polymerase II transcription machinery in yeast.
AB  - TAP tags and dot blot analysis have been used to measure the amounts of RNA
      polymerase II transcription proteins in crude yeast extracts. The measurements
      showed comparable amounts of RNA polymerase II, TFIIE, and TFIIF, lower levels of
      TBP and TFIIB, and still lower levels of Mediator and TFIIH. These findings are
      consistent with the presumed roles of the transcription proteins, but do not
      support the idea of their recruitment in a single large complex to RNA polymerase
      II promoters. The approach employed here can be readily extended to quantitative
      analysis of the entire yeast proteome.

PMID- 11591728
TI  - The plasmamembrane calmodulin-dependent calcium pump: a major regulator of nitric
      oxide synthase I.
AB  - The plasma membrane calcium/calmodulin-dependent calcium ATPase (PMCA) (Shull,
      G.E., and J. Greeb. 1988. J. Biol. Chem. 263:8646-8657; Verma, A.K., A.G.
      Filoteo, D.R. Stanford, E.D. Wieben, J.T. Penniston, E.E. Strehler, R. Fischer,
      R. Heim, G. Vogel, S. Mathews, et al. 1988. J. Biol. Chem. 263:14152-14159;
      Carafoli, E. 1997. Basic Res. Cardiol. 92:59-61) has been proposed to be a
      regulator of calcium homeostasis and signal transduction networks of the cell.
      However, little is known about its precise mechanisms of action. Knock-out of
      (mainly neuronal) isoform 2 of the enzyme resulted in hearing loss and balance
      deficits due to severe inner ear defects, affecting formation and maintenance of
      otoconia (Kozel, P.J., R.A. Friedman, L.C. Erway, E.N. Yamoah, L.H. Liu, T.
      Riddle, J.J. Duffy, T. Doetschman, M.L. Miller, E.L. Cardell, and G.E. Shull.
      1998. J. Biol. Chem. 273:18693-18696). Here we demonstrate that PMCA 4b is a
      negative regulator of nitric oxide synthase I (NOS-I, nNOS) in HEK293 embryonic
      kidney and neuro-2a neuroblastoma cell models. Binding of PMCA 4b to NOS-I was
      mediated by interaction of the COOH-terminal amino acids of PMCA 4b and the PDZ
      domain of NOS-I (PDZ: PSD 95/Dlg/ZO-1 protein domain). Increasing expression of
      wild-type PMCA 4b (but not PMCA mutants unable to bind PDZ domains or devoid of
      Ca2+-transporting activity) dramatically downregulated NO synthesis from wild
      type NOS-I. A NOS-I mutant lacking the PDZ domain was not regulated by PMCA,
      demonstrating the specific nature of the PMCA-NOS-I interaction. Elucidation of
      PMCA as an interaction partner and major regulator of NOS-I provides evidence for
      a new dimension of integration between calcium and NO signaling pathways.

PMID- 11591729
TI  - Evidence that Golgi structure depends on a p115 activity that is independent of
      the vesicle tether components giantin and GM130.
AB  - Inhibition of the putative coatomer protein I (COPI) vesicle tethering complex,
      giantin-p115-GM130, may contribute to mitotic Golgi breakdown. However, neither
      this, nor the role of the giantin-p115-GM130 complex in the maintenance of Golgi
      structure has been demonstrated in vivo. Therefore, we generated antibodies
      directed against the mapped binding sites in each protein of the complex and
      injected these into mammalian tissue culture cells. Surprisingly, the injected
      anti-p115 and antigiantin antibodies caused proteasome-mediated degradation of
      the corresponding antigens. Reduction of p115 levels below detection led to COPI
      dependent Golgi fragmentation and apparent accumulation of Golgi-derived
      vesicles. In contrast, neither reduction of giantin below detectable levels, nor
      inhibition of p115 binding to GM130, had any detectable effect on Golgi structure
      or Golgi reassembly after cell division or brefeldin A washout. These
      observations indicate that inhibition of p115 can induce a mitotic-like Golgi
      disassembly, but its essential role in Golgi structure is independent of its
      Golgi-localized binding partners giantin and GM130.

PMID- 11591730
TI  - APAF1 is a key transcriptional target for p53 in the regulation of neuronal cell
      death.
AB  - p53 is a transcriptional activator which has been implicated as a key regulator
      of neuronal cell death after acute injury. We have shown previously that p53
      mediated neuronal cell death involves a Bax-dependent activation of caspase 3;
      however, the transcriptional targets involved in the regulation of this process
      have not been identified. In the present study, we demonstrate that p53 directly
      upregulates Apaf1 transcription as a critical step in the induction of neuronal
      cell death. Using DNA microarray analysis of total RNA isolated from neurons
      undergoing p53-induced apoptosis a 5-6-fold upregulation of Apaf1 mRNA was
      detected. Induction of neuronal cell death by camptothecin, a DNA-damaging agent
      that functions through a p53-dependent mechanism, resulted in increased Apaf1
      mRNA in p53-positive, but not p53-deficient neurons. In both in vitro and in vivo
      neuronal cell death processes of p53-induced cell death, Apaf1 protein levels
      were increased. We addressed whether p53 directly regulates Apaf1 transcription
      via the two p53 consensus binding sites in the Apaf1 promoter. Electrophoretic
      mobility shift assays demonstrated p53-DNA binding activity at both p53 consensus
      binding sequences in extracts obtained from neurons undergoing p53-induced cell
      death, but not in healthy control cultures or when p53 or the p53 binding sites
      were inactivated by mutation. In transient transfections in a neuronal cell line
      with p53 and Apaf1 promoter-luciferase constructs, p53 directly activated the
      Apaf1 promoter via both p53 sites. The importance of Apaf1 as a p53 target gene
      in neuronal cell death was evaluated by examining p53-induced apoptotic pathways
      in primary cultures of Apaf1-deficient neurons. Neurons treated with camptothecin
      were significantly protected in the absence of Apaf1 relative to those derived
      from wild-type littermates. Together, these results demonstrate that Apaf1 is a
      key transcriptional target for p53 that plays a pivotal role in the regulation of
      apoptosis after neuronal injury.

PMID- 11591731
TI  - Functional characterization of the KNOLLE-interacting t-SNARE AtSNAP33 and its
      role in plant cytokinesis.
AB  - Cytokinesis requires membrane fusion during cleavage-furrow ingression in animals
      and cell plate formation in plants. In Arabidopsis, the Sec1 homologue KEULE
      (KEU) and the cytokinesis-specific syntaxin KNOLLE (KN) cooperate to promote
      vesicle fusion in the cell division plane. Here, we characterize AtSNAP33, an
      Arabidopsis homologue of the t-SNARE SNAP25, that was identified as a KN
      interactor in a yeast two-hybrid screen. AtSNAP33 is a ubiquitously expressed
      membrane-associated protein that accumulated at the plasma membrane and during
      cell division colocalized with KN at the forming cell plate. A T-DNA insertion in
      the AtSNAP33 gene caused loss of AtSNAP33 function, resulting in a lethal dwarf
      phenotype. atsnap33 plantlets gradually developed large necrotic lesions on
      cotyledons and rosette leaves, resembling pathogen-induced cellular responses,
      and eventually died before flowering. In addition, mutant seedlings displayed
      cytokinetic defects, and atsnap33 in combination with the cytokinesis mutant keu
      was embryo lethal. Analysis of the Arabidopsis genome revealed two further SNAP25
      like proteins that also interacted with KN in the yeast two-hybrid assay. Our
      results suggest that AtSNAP33, the first SNAP25 homologue characterized in
      plants, is involved in diverse membrane fusion processes, including cell plate
      formation, and that AtSNAP33 function in cytokinesis may be replaced partially by
      other SNAP25 homologues.

PMID- 11591732
TI  - Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells
      and monocytes, regulates angiogenesis and endothelial cell cytokine production.
AB  - A novel secreted cytokine, termed IL-17F, was cloned using nested RACE PCR. This
      cytokine bears homology to IL-17. IL-17F was expressed only in activated CD4(+) T
      cells and activated monocytes. Recombinant human IL-17F did not stimulate the
      proliferation of hematopoietic progenitors or the migration of mature leukocytes.
      However, it markedly inhibited the angiogenesis of human endothelial cells and
      induced endothelial cells to produce IL-2, TGF-beta, and monocyte chemoattractant
      protein-1.

PMID- 11591733
TI  - Cutting edge: the absence of C3 demonstrates a role for complement in Th2
      effector functions in a murine model of pulmonary allergy.
AB  - Asthma is a chronic disease of the lung resulting from airway obstruction.
      Although the initiating causes are not entirely clear, the airway inflammation in
      asthma is associated with Th2 lymphocytes and their cytokines, particularly IL-4,
      which play a prominent role in this disease by regulating airway
      hyperresponsiveness, eosinophil activation, and IgE synthesis. Historically,
      complement was not thought to contribute to the pathogenesis of asthma. However,
      using C3-deficient mice in an allergen-induced model of pulmonary allergy, we
      demonstrate that complement may impact key features of this disease. When
      challenged with allergen, mice deficient in C3 exhibit diminished airway
      hyperresponsiveness and lung eosinophilia. Furthermore, these mice also have
      dramatically reduced numbers of IL-4-producing cells and attenuated Ag-specific
      IgE and IgG1 responses. Collectively, these results demonstrate that C3-deficient
      mice have significantly altered allergic lung responses and indicate a role for
      the complement system in promoting Th2 effector functions in asthma.

PMID- 11591734
TI  - Induction of IL-10 and inhibition of experimental arthritis are specific features
      of microbial heat shock proteins that are absent for other evolutionarily
      conserved immunodominant proteins.
AB  - Bacterial heat shock proteins (hsp) are evolutionary conserved immunodominant
      proteins that manifest amino acid homologies with hsp present in mammalian cells.
      Preimmunization with mycobacterial hsp65 has been found to protect against
      various forms of experimental arthritis. As these protective effects have
      previously been attributed to induction of self homologue cross-reactive T cell
      responses, the question was raised as to whether this protective effect could be
      extended to other highly conserved and immunodominant microbial Ags with
      mammalian homologues. Therefore, we immunized Lewis rats with conserved bacterial
      Ags (superoxide dismutase, aldolase, GAPDH, and hsp70). Although all Ags appeared
      highly immunogenic, we only found a protective effect in experimental arthritis
      after immunization with bacterial hsp70. The protective effect of hsp70 was
      accompanied with a switch in the subclasses of hsp70-specific Abs, suggesting the
      induction of Th2-like response. The most striking difference between immunization
      with hsp70 and all other immunodominant Ags was the expression of IL-10 found
      after immunization with hsp70. Even more, while immunization with hsp70 led to Ag
      induced production of IL-10 and IL-4, immunization with aldolase led to increased
      production of IFN-gamma and TNF-alpha. Thus, the protective effect of conserved
      immunodominant proteins in experimental arthritis seems to be a specific feature
      of hsp. Therefore, hsp may offer unique possibilities for immunological
      intervention in inflammatory diseases.

PMID- 11591735
TI  - Persistence of dominant T cell clones in accepted solid organ transplants.
AB  - Donor/recipient MHC class II matching is beneficial to the survival of allogeneic
      kidneys in humans and swine. In the latter, tolerance to class I-disparate grafts
      can be induced by a short course of immunosuppression, a peripheral mechanism
      that implicates regulatory T cells. Absence of treatment will lead to prompt
      rejection. Rejected grafts are infiltrated by dominant alloaggressive T cells,
      whereas there is still speculation on the specificity and function of T cells
      invading accepted tissues. To characterize the TCR repertoire of graft
      infiltrating T cells (GITC) in accepted kidneys, we have used the RT-PCR-based
      spectratyping technique to assess the length polymorphism of the porcine TCRbeta
      chain complementary-determining region 3 (CDR3). Results show that T cells
      infiltrating accepted kidneys (n = 5) express a restricted polymorphism of the
      CDR3 length, whereas PBL from the same animal have the polymorphic distribution
      of CDR3 lengths found in naive animals; that the skewed Vbeta repertoire in
      accepted grafts involved distinct Vbeta subfamilies in otherwise MHC-identical
      recipient animals; that GITC clonal dominance is not caused by immunosuppression
      because a second kidney, accepted without drug treatment, exhibits the same TCR
      Vbeta CDR3 profiles than those detected in the first graft; and that intragraft
      clonal dominance intensifies with time, indicating progressive preeminence of
      nonaggressive GITC clones. Collectively, these data represent the first example,
      in a preclinical model, of the emergence of nonaggressive intragraft clones,
      which may be involved in the induction/maintenance of local tolerance to
      allogeneic tissues.

PMID- 11591736
TI  - Enhancement of mast cell survival: a novel function of some secretory
      phospholipase A(2) isotypes.
AB  - This study tested the hypothesis that certain secretory phospholipase A(2)
      (sPLA(2)) isotypes act in a cytokine-like fashion through cell surface receptors
      to influence mast cell survival. Initial experiments revealed that sPLA(2)
      activity and sPLA(2) receptor expression are increased, and mast cells lost their
      capacity to maintain membrane asymmetry upon cytokine depletion. Groups IB and
      III, but not group IIA PLA(2), prevented the loss of membrane asymmetry.
      Similarly, group IB prevented nucleosomal DNA fragmentation in mast cells.
      Providing putative products of sPLA(2) hydrolysis to cytokine-depleted mast cells
      did not influence survival. Furthermore, catalytic inactivation of sPLA(2) did
      not alter its capacity to prevent apoptosis. Inhibition of protein synthesis
      using cycloheximide or actinomycin reversed the antiapoptotic effect of sPLA(2).
      Additionally, both wild-type and catalytically inactive group IB PLA(2) induced
      IL-3 synthesis in mast cells. However, adding IL-3-neutralizing Ab did not change
      Annexin V(FITC) binding and only partially inhibited thymidine incorporation in
      sPLA(2)-supplemented mast cells. In contrast, IL-3-neutralizing Ab inhibited both
      Annexin V(FITC) binding and thymidine incorporation in mast cells maintained with
      IL-3. sPLA(2) enhanced phosphoinositide 3'-kinase activity, and a specific
      inhibitor of phosphoinositide 3'-kinase reversed the antiapoptotic effects of
      sPLA(2). Likewise, sPLA(2) increased the degradation of I-kappaBalpha, and
      specific inhibitors of nuclear factor kappa activation (NF-kappaB) reversed the
      antiapoptotic effects of sPLA(2). Together, these experiments reveal that certain
      isotypes of sPLA(2) enhance the survival of mast cells in a cytokine-like fashion
      by activating antiapoptotic signaling pathways independent of IL-3 and probably
      via sPLA(2) receptors rather than sPLA(2) catalytic products.

PMID- 11591737
TI  - Unique signaling properties of B cell antigen receptor in mature and immature B
      cells: implications for tolerance and activation.
AB  - Immature B cells display increased sensitivity to tolerance induction compared
      with their mature counterparts. The molecular mechanisms underlying these
      differences are poorly defined. In this study, we demonstrate unique maturation
      stage-dependent differences in B cell Ag receptor (BCR) signaling, including BCR
      mediated calcium mobilization responses. Immature B cells display greater
      increases in intracellular calcium concentrations following Ag stimulation. This
      has consequences for the induction of biologically relevant responses: immature B
      cells require lower Ag concentrations for activation than mature B cells, as
      measured by induction of receptor editing and CD86 expression, respectively. BCR
      induced tyrosine phosphorylation of CD79a, Lyn, B cell linker protein, and
      phospholipase Cgamma2 is enhanced in immature B cells and they exhibit greater
      capacitative calcium entry in response to Ag. Moreover, B cell linker protein,
      Bruton's tyrosine kinase, and phospholipase Cgamma2, which are crucial for the
      induction of calcium mobilization responses, are present at approximately 3-fold
      higher levels in immature B cells, potentially contributing to increased
      mobilization of calcium. Consistent with this possibility, we found that the
      previously reported lack of inositol-1,4,5-triphosphate production in immature B
      cells may be explained by enhanced inositol-1,4,5-triphosphate breakdown. These
      data demonstrate that multiple mechanisms guarantee increased Ag-induced
      mobilization of calcium in immature B cells and presumably ensure elimination of
      autoreactive B cells from the repertoire.

PMID- 11591738
TI  - Regulation of NKT cells by Ly49: analysis of primary NKT cells and generation of
      NKT cell line.
AB  - TCRalphabeta(+)NK1.1(+) (NKT) cells are known to express various NK cell
      associated molecules including the Ly49 family of receptors for MHC class I, but
      its functional significance has been unclear. Here, we examined the expression of
      Ly49A, C/I and G2 on various NKT cell populations from normal and MHC class I
      deficient C57BL/6 mice as well as their responsiveness to alpha
      galactosylceramide (alpha-GalCer), a potent stimulator of CD1d-restricted NKT
      cells. The frequency and the level of Ly49 expression varied among NKT cells from
      different tissues, and were regulated by the expression of MHC class I and CD1d
      in the host. Stimulation of various NKT cells with alpha-GalCer suggested that
      Ly49 expression inversely correlates with the responsiveness of NKT cells to
      alpha-GalCer. Moreover, alpha-GalCer presented by normal dendritic cells
      stimulated purified Ly49(-), but not Ly49(+), splenic NKT cells, whereas MHC
      class I-deficient dendritic cells presented alpha-GalCer to both Ly49(+) and
      Ly49(-) NKT cells equally well. Therefore, MHC class I on APCs seems to inhibit
      activation of NKT cells expressing Ly49. To further characterize CD1d-restricted
      NKT cells, we generated an alpha-GalCer-responsive NKT cell line from thymocytes.
      The line could only be generated from Ly49(-)NK1.1(+)CD4(+) thymocytes but not
      from other NKT cell subsets, and it lost expression of NK1.1 and CD4 during
      culture. Together, these results indicate the functional significance of Ly49
      expression on NKT cells.

PMID- 11591739
TI  - Neonatal exposure to antigen primes the immune system to develop responses in
      various lymphoid organs and promotes bystander regulation of diverse T cell
      specificities.
AB  - Neonatal exposure to Ag has always been considered suppressive for immunity.
      Recent investigations, however, indicated that the neonatal immune system could
      be guided to develop immunity. For instance, delivery of a proteolipid protein
      (PLP) peptide on Ig boosts the neonatal immune system to develop responses upon
      challenge with the PLP peptide later. Accordingly, mice given Ig-PLP at birth and
      challenged with the PLP peptide as adults developed proliferative T cells in the
      lymph node that produced IL-4 instead of the usual Th1 cytokines. However, the
      spleen was unresponsive unless IL-12 was provided. Herein, we wished to determine
      whether such a neonatal response is intrinsic to the PLP peptide or could develop
      with an unrelated myelin peptide as well as whether the T cell deviation is able
      to confer resistance to autoimmunity involving diverse T cell specificities.
      Accordingly, the amino acid sequence 87-99 of myelin basic protein was expressed
      on the same Ig backbone, and the resulting Ig-myelin basic protein chimera was
      tested for induction of neonatal immunity and protection against experimental
      allergic encephalomyelitis. Surprisingly, the results indicated that immunity
      developed in the lymph node and spleen, with deviation of T cells occurring in
      both organs. More striking, the splenic T cells produced IL-10 in addition to IL
      4, providing an environment that facilitated bystander deviation of responses to
      unrelated epitopes and promoted protection against experimental allergic
      encephalomyelitis involving diverse T cell specificities. Thus, neonatal exposure
      to Ag can prime responses in various organs and sustain regulatory functions
      effective against diverse autoreactive T cells.

PMID- 11591740
TI  - Purification of Ag-specific T lymphocytes after direct peripheral blood
      mononuclear cell stimulation followed by CD25 selection. I. Application to CD4(+)
      or CD8(+) cytomegalovirus phosphoprotein pp65 epitope determination.
AB  - The two main constraints that currently limit a broader usage of T cell therapy
      against viruses are the delay required to obtain specific T cells and the safety
      of the selection procedure. In the present work we developed a generally
      applicable strategy that eliminates the need for APC for timing reasons, and the
      need for infectious viral strains for safety concerns. As a model, we used the
      selection of T lymphocytes specific for the immunodominant CMV phosphoprotein
      pp65. PBMC from healthy seropositive donors were first depleted of IL-2R alpha
      chain CD25(+) cells and were then stimulated for 24-96 h with previously defined
      peptide Ags or with autologous PBMC infected with a canarypox viral vector
      encoding the total pp65 protein (ALVAC-pp65). Subsequent immunomagnetic
      purification of newly CD25-expressing cells allowed efficient recovery of T
      lymphocytes specific for the initial stimuli, i.e., for the already known
      immunodominant epitope corresponding to the peptides used as a model or for newly
      defined epitopes corresponding to peptides encoded by the transfected pp65
      protein. Importantly, we demonstrated that direct PBMC stimulation allowed
      recovery not only of CD8(+) memory T lymphocytes, but also of the CD4(+) memory T
      cells, which are known to be crucial to ensure persistence of adoptively
      transferred immune memory. Finally, our analysis of pp65-specific T cells led to
      the identification of several new helper and cytotoxic epitopes. This work thus
      demonstrates the feasibility of isolating memory T lymphocytes specific for a
      clinically relevant protein without the need to prepare APC, to use infectious
      viral strains, or to identify immunodominant epitopes.

PMID- 11591741
TI  - Peptide length variants p2Ca and QL9 present distinct conformations to L(d)
      specific T cells.
AB  - Recent advances have provided insights into how the TCR interacts with
      MHC/peptide complexes and a rationale to predict optimal epitopes for MHC binding
      and T cell recognition. For example, peptides of nine residues are predicted to
      be optimal for binding to H2-L(d), although 8 mer epitopes have also been
      identified. It has been predicted that 8 mer and 9 mer length variant peptides
      bound to L(d) present identical epitopes to T cells. However, in contrast to this
      prediction, we demonstrate here that the 8 mer peptide p2Ca and its 9 mer length
      variant QL9, extended by an N-terminal glutamine, assume distinct conformations
      when bound to L(d). We generated self-L(d)-restricted CTL clones specific for
      p2Ca that recognize L(d)/QL9 poorly if at all. This result is in sharp contrast
      to what has been observed with L(d)-alloreactive T cells that possess a much
      higher affinity for L(d)/QL9 than for L(d)/p2Ca. Alanine substitutions of the N
      terminal residues of the QL9 peptide rescue detection by these self-L(d)/p2Ca
      specific T cells, but decrease recognition by the L(d)-alloreactive 2C T cell
      clone. In addition, 2C T cell recognition of the p2Ca peptide is affected by
      different alanine substitutions compared with 2C T cell recognition of the QL9
      peptide. These data clearly demonstrate that the p2Ca and QL9 peptides assume
      distinct conformations when bound to L(d) and, furthermore, demonstrate that
      there is flexibility in peptide binding within the MHC class I cleft.

PMID- 11591742
TI  - Induction of CTL and nonpolarized Th cell responses by CD8alpha(+) and CD8alpha(
      ) dendritic cells.
AB  - Two distinct dendritic cell (DC) subpopulations have been evidenced in mice on
      the basis of their differential CD8alpha expression and their localization in
      lymphoid organs. Several reports suggest that CD8alpha(+) and CD8alpha(-) DC
      subsets could be functionally different. In this study, using a panel of MHC
      class I- and/or class II-restricted peptides, we analyzed CD4(+) and CD8(+) T
      cell responses obtained after i.v. injection of freshly purified peptide-pulsed
      DC subsets. First, we showed that both DC subsets efficiently induce specific CTL
      responses and Th1 cytokine production in the absence of CD4(+) T cell priming.
      Second, we showed that in vivo activation of CD4(+) T cells by CD8alpha(+) or
      CD8alpha(-) DC, injected i.v., leads to a nonpolarized Th response with
      production of both Th1 and Th2 cytokines. The CD8alpha(-) subset induced a higher
      production of Th2 cytokines such as IL-4 and IL-10 than the CD8alpha(+) subset.
      However, IL-5 was produced by CD4(+) T cells activated by both DC subsets. When
      both CD4(+) and CD8(+) T cells were primed by DC injected i.v., a similar pattern
      of cytokines was observed, but, under these conditions, Th1 cytokines were mainly
      produced by CD8(+) T cells, while Th2 cytokines were produced by CD4(+) T cells.
      Thus, this study clearly shows that CD4(+) T cell responses do not influence the
      development of specific CD8(+) T cell cytotoxic responses induced either by
      CD8alpha(+) or CD8alpha(-) DC subsets.

PMID- 11591743
TI  - Immunotoxins containing recombinant anti-CTLA-4 single-chain fragment variable
      antibodies and saporin: in vitro results and in vivo effects in an acute
      rejection model.
AB  - Immunotoxins containing recombinant human-derived single-chain fragment variable
      (scFv) reagents (83 and 40) against CTLA-4 (CD152) linked to saporin, a ribosome
      inactivating protein, were prepared and tested on CD3/CD28-activated T
      lymphocytes, MLRs, CTLA-4-positive cell lines, and hemopoietic precursors.
      Immunotoxins induced apoptosis in activated T lymphocytes and were able to
      specifically inhibit MLR between T lymphocytes and dendritic cells. The 83
      saporin immunotoxin also inhibited the T cell activation in an MLR between T
      lymphocytes and an EBV-positive lymphoblastoid B cell line. Toxicity tests on
      hemopoietic precursors showed little or no effects in inhibiting colonies'
      growth. As the 83 scFv Ab was reactive also with activated mouse T lymphocytes,
      83-saporin was tested in a model of tumor rejection consisting of C57BL/6 mice
      bearing a murine H.end endothelioma cell line, derived from DBA/2 mice. The
      lymphoid infiltration due to the presence of the tumor was reduced to a high
      extent, demonstrating that the immunotoxin was actually available and active in
      vivo. Thus, taking the results altogether, this study might represent a new
      breakthrough for immunotherapy, showing the possibility of targeting CTLA-4 to
      kill activated T cells, using conjugates containing scFv Abs and type 1 ribosome
      inactivating protein.

PMID- 11591744
TI  - Inhibition of the death receptor pathway by cFLIP confers partial engraftment of
      MHC class I-deficient stem cells and reduces tumor clearance in perforin
      deficient mice.
AB  - NK cells mediate acute rejection of MHC class I-deficient bone marrow cell (BMC)
      grafts. However, the exact cytotoxic mechanisms of NK cells during acute BMC
      graft rejection are not well defined. Although the granule exocytosis pathway
      plays a major role in NK cell-mediated rejection, alternative perforin
      independent mechanisms also exist. By analyzing the anti-apoptotic effects of
      cellular Fas-associated death domain-like IL-1-converting enzyme-inhibitory
      protein (cFLIP) overexpression, we investigated the possible role of death
      receptor-induced apoptosis in NK cell-mediated cytotoxicity. In the absence of
      perforin, we found that cFLIP overexpression reduces lysis of tumor cells by NK
      cells in vitro and in vivo. In addition, perforin-deficient NK cells were
      impaired in their ability to acutely reject cFLIP-overexpressing TAP-1 knockout
      stem cells. These results emphasize the importance of NK cell death receptor
      mediated killing during BMC grafts in the absence of perforin.

PMID- 11591745
TI  - HIV envelope protein inhibits MHC class I presentation of a cytomegalovirus
      protective epitope.
AB  - CTL recognize peptides that derive from viral protein Ags by proteolytic
      processing and are presented by MHC class I molecules. In this study we tested
      whether coexpression of viral Ags in the same cell leads to competition between
      them. To this end, two L(d)-restricted epitopes derived from HIV-1 envelope gp160
      (ENV) and from CMV pp89 phosphoprotein were coexpressed. HIV ENV strain IIIB, but
      not MN variant, impaired recognition by specific CTL of CMV pp89 epitope 9pp89.
      Susceptibility to inhibition after ENV coexpression was inversely related to the
      amount of antigenic 9pp89 peptide processed from different antigenic constructs.
      In line with it, competition decreased the yield of naturally processed antigenic
      9pp89 peptide bound to MHC class I molecules in coinfected cells. Also, point
      mutants of the presenting MHC class I molecule differed in their competition
      pattern. Collectively, the data imply that competition operates at the step of
      MHC-peptide complex assembly or stabilization. We conclude that, although not the
      rule, in certain combinations there is interference between different Ags
      expressed in the same cell and presented by the same MHC class I allele. These
      studies have implications for vaccine development and for understanding
      immunodominance.

PMID- 11591746
TI  - Activation of CD25(+)CD4(+) regulatory T cells by oral antigen administration.
AB  - CD25(+)CD4(+) T cells are naturally occurring regulatory T cells that are anergic
      and have suppressive properties. Although they can be isolated from the spleens
      of normal mice, there are limited studies on how they can be activated or
      expanded in vivo. We found that oral administration of OVA to OVA TCR transgenic
      mice resulted in a modification of the ratio of CD25(+)CD4(+) to CD25(-)CD4(+)
      cells with an increase of CD25(+)CD4(+) T cells accompanied by a decrease of
      CD25(-)CD4(+) T cells. The relative increase in CD25(+)CD4(+) T cells persisted
      for as long as 4 wk post feeding. We also found that CTLA-4 was dominantly
      expressed in CD25(+)CD4(+) T cells and there was an increase in the percentage of
      CD25(+)CD4(+) T cells expressing CTLA-4 in OVA-fed mice. In contrast to CD25(
      )CD4(+) cells, CD25(+)CD4(+) cells from fed mice proliferated only minimally to
      OVA or anti-CD3 and secreted IL-10 and elevated levels of TGF-beta(1) following
      anti-CD3 stimulation. CD25(+)CD4(+) cells from fed mice suppressed the
      proliferation of CD25(-)CD4(+) T cells in vitro more potently than CD25(+)CD4(+)
      T cells isolated from unfed mice, and this suppression was partially reversible
      by IL-10 soluble receptor or TGF-beta soluble receptor and high concentration of
      anti-CTLA-4. With anti-CD3 stimulation, CD25(+)CD4(+) cells from unfed mice
      secreted IFN-gamma, whereas CD25(+)CD4(+) cells from fed mice did not. Adoptive
      transfer of CD25(+)CD4(+) T cells from fed mice suppressed in vivo delayed-type
      hypersensitivity responses in BALB/c mice. These results demonstrate an Ag
      specific in vivo method to activate CD25(+)CD4(+) regulatory T cells and suggest
      that they may be involved in oral tolerance.

PMID- 11591747
TI  - Visualization and characterization of respiratory syncytial virus F-specific
      CD8(+) T cells during experimental virus infection.
AB  - CTL play a major role in the clearance of respiratory syncytial virus (RSV)
      during experimental pulmonary infection. The fusion (F) glycoprotein of RSV is a
      protective Ag that elicits CTL and Ab response against RSV infection in BALB/c
      mice. We used the strategy of screening a panel of overlapping synthetic peptides
      corresponding to the RSV F protein and identified an immunodominant H-2K(d)
      restricted epitope (F(85-93); KYKNAVTEL) recognized by CD8(+) T cells from BALB/c
      mice. We enumerated the F-specific CD8(+) T cell response in the lungs of
      infected mice by flow cytometry using tetramer staining and intracellular
      cytokine synthesis. During primary infection, F(85-93)-specific effector CD8(+) T
      cells constitute approximately 4.8% of pulmonary CD8(+) T cells at the peak of
      the primary response (day 8), whereas matrix 2-specific CD8(+) T cells
      constituted approximately 50% of the responding CD8(+) T cell population in the
      lungs. When RSV F-immune mice undergo a challenge RSV infection, the F-specific
      CD8(+) T cell response is accelerated and dominates, whereas the primary response
      to the matrix 2 epitope in the lungs is reduced by approximately 20-fold. In
      addition, we found that activated F-specific effector CD8(+) T cells isolated
      from the lungs of RSV-infected mice exhibited a lower than expected frequency of
      IFN-gamma-producing CD8(+) T cells and were significantly impaired in ex vivo
      cytolytic activity compared with competent F-specific effector CD8(+) T cells
      generated in vitro. The significance of these results for the regulation of the
      CD8(+) T cell response to RSV is discussed.

PMID- 11591748
TI  - Resting and activation-dependent ion channels in human mast cells.
AB  - The mechanism of mediator secretion from mast cells in disease is likely to
      include modulation of ion channel activity. Several distinct Ca(2+), K(+), and
      Cl(-) conductances have been identified in rodent mast cells, but there are no
      data on human mast cells. We have used the whole-cell variant of the patch clamp
      technique to characterize for the first time macroscopic ion currents in purified
      human lung mast cells and human peripheral blood-derived mast cells at rest and
      following IgE-dependent activation. The majority of both mast cell types were
      electrically silent at rest with a resting membrane potential of around 0 mV.
      Following IgE-dependent activation, >90% of human peripheral blood-derived mast
      cells responded within 2 min with the development of a Ca(2+)-activated K(+)
      current exhibiting weak inward rectification, which polarized the cells to around
      -40 mV and a smaller outwardly rectifying Ca(2+)-independent Cl(-) conductance.
      Human lung mast cells showed more heterogeneity in their response to anti-IgE,
      with Ca(2+)-activated K(+) currents and Ca(2+)-independent Cl(-) currents
      developing in approximately 50% of cells. In both cell types, the K(+) current
      was blocked reversibly by charybdotoxin, which along with its
      electrophysiological properties suggests it is carried by a channel similar to
      the intermediate conductance Ca(2+)-activated K(+) channel. Charybdotoxin did not
      consistently attenuate histamine or leukotriene C(4) release, indicating that the
      Ca(2+)-activated K(+) current may enhance, but is not essential for, the release
      of these mediators.

PMID- 11591749
TI  - CD4(+)CD25(+) T cells facilitate the induction of T cell anergy.
AB  - T cell anergy is characterized by the inability of the T cell to produce IL-2 and
      proliferate. It is reversible by the addition of exogenous IL-2. A similar state
      of unresponsiveness is observed when the proliferative response of murine
      CD4(+)CD25(-) T cells is suppressed in vitro by coactivated CD4(+)CD25(+) T
      cells. We have developed a suppression system that uses beads coated with anti
      CD3 and anti-CD28 Abs as surrogate APCs to study the interaction of CD4(+)CD25(+)
      and CD4(+)CD25(-) T cells in vitro. CD4(+)CD25(+) T cell-induced suppression, in
      this model, was not abrogated by blocking the B7-CTLA-4 pathway. When the
      CD4(+)CD25(-) T cells were separated from the CD4(+)CD25(+) suppressor cells
      after 24 h of coactivation by the Ab-coated beads, the CD4(+)CD25(-) T cells were
      unable to proliferate or to produce IL-2 upon restimulation. The induction of
      this anergic phenotype in the CD4(+)CD25(-) T cells correlated with the up
      regulated expression of the gene related to anergy in lymphocytes (GRAIL), a
      novel anergy-related gene that acts as a negative regulator of IL-2
      transcription. This system constitutes a novel mechanism of anergy induction in
      the presence of costimulation.

PMID- 11591750
TI  - Hapten addition to an MHC class I-binding peptide causes substantial adjustments
      of the TCR structure of the responding CD8(+) T cells.
AB  - T cell responses against hapten-modified peptides play an important role in the
      pathogenesis of certain diseases, including contact dermatitis and allergy.
      However, the structural features of TCRs recognizing bulky, potentially mobile
      hapten groups remain poorly defined. To analyze the structural basis of TCR
      recognition of defined hapten-modified peptides, the immunodominant octapeptide
      derived from vesicular stomatitis virus nucleoprotein (VSV8) was modified with a
      trinitrophenyl (TNP) group at the primary TCR contact residues (position 4 or 6)
      and used for immunization of mice carrying either the TCR alpha- or beta-chain of
      a VSV8 (unmodified)/H-2K(b)-specific CTL clone as a transgene. Such mice allow
      independent analysis of one TCR chain by maintaining the other fixed. The TCR V
      gene usage of the responding T cell population was specifically altered depending
      upon the presence of the TNP group and its position on the peptide. The CDR3
      sequences of the TNP-modified peptide-specific TCRs showed a preferential J
      region usage in both the CDR3alpha and beta loops, indicating that the J regions
      of both CDR3s are critical for recognition of TNP-modified peptides. In contrast
      to our previous observations showing the prime importance of CDR3beta residues
      encoded by D-segment or N-addition nucleotides for recognition of position 6 of
      unmodified VSV8, our studies of TNP-modified peptides demonstrate the importance
      of the Jbeta region, while the Jalpha region was crucial for recognizing both TNP
      modified and unmodified peptides. These data suggest that different structural
      strategies are utilized by the CDR3alpha and beta loops to allow interaction with
      a haptenated peptide.

PMID- 11591751
TI  - Regression of extensive pulmonary metastases in mice by adoptive transfer of
      antigen-specific CD8(+) CTL reactive against tumor cells expressing a naturally
      occurring rejection epitope.
AB  - In this study, we developed a mouse model of adoptive immunotherapy reflecting
      immune recognition of syngeneic tumor cells naturally expressing an endogenous
      rejection Ag. Specifically, in a pulmonary metastases model, we examined the
      potency and maintenance of an antitumor CD8(+) CTL response in vivo, as well as
      its effectiveness against an "extensive" tumor burden. The approach taken was to
      first generate tumor-specific CTL from mice challenged with the CMS4 sarcoma
      coadministered with anti-CTLA4 mAb, which has been shown to facilitate the
      induction of Ag-specific T cell responses in vivo. An H-2L(d)-restricted nonamer
      peptide, derived from an endogenous murine leukemia provirus was identified as a
      CMS4-reactive CTL epitope based upon the following: CTL cross-recognition of
      another syngeneic tumor cell line (CT26 colon carcinoma) previously characterized
      to express that gene product; sensitization of Ag-negative lymphoblasts or P815
      targets with the peptide; and by cold target inhibition assays. In vivo, the
      adoptive transfer of CMS4-reactive CTL (> or =1 x 10(6)) resulted in nearly the
      complete regression of 3-day established lung metastases. Furthermore, mice that
      rejected CMS4 following a single adoptive transfer of CTL displayed antitumor
      activity to a rechallenge 45 days later, not only in the lung, but also at a s.c.
      distal site. Lastly, the adoptive transfer of CTL to mice harboring extensive
      pulmonary metastases (> 150 nodules) led to a substantial reduction in tumor
      burden. Overall, these data suggest that the adoptive transfer of tumor-specific
      CTL may have therapeutic potential for malignancies that proliferate in or
      metastasize to the lung.

PMID- 11591752
TI  - A schistosome-expressed immunomodulatory glycoconjugate expands peritoneal Gr1(+)
      macrophages that suppress naive CD4(+) T cell proliferation via an IFN-gamma and
      nitric oxide-dependent mechanism.
AB  - Lacto-N-fucopentaose III (LNFPIII) is found in human milk and on the Th2 driving
      helminth parasite Schistosoma mansoni. This pentasaccharide drives Th2-type
      responses in vivo and in vitro when conjugated to a carrier. In an attempt to
      further understand early events in Th1 to Th2 switching, we examined phenotypic
      and functional changes in peritoneal cell populations in BALB/c and SCID mice
      following LNFPIII-dextran injection. We found that i.p. injection with LNFPIII
      dextran resulted in rapid (<20 h) expansion of the Gr1(+) subpopulation of
      F4/80(+)/CD11b(+) peritoneal cells, comprising up to 75% of F4/80(+)/CD11b(+)
      peritoneal cells compared with 18% in uninjected or dextran-injected mice.
      Functionally, these cells suppressed anti-CD3- and anti-CD28-induced
      proliferation of naive CD4(+) T cells. LNFPIII-dextran also expanded functional
      Gr1(+) suppressor macrophages in SCID mice, demonstrating that expansion and
      function of suppressor cells did not require T cells. Suppression in both BALB/c
      and SCID mice was NO and IFN-gamma dependent, as addition of inhibitors of
      inducible NO synthase (N(G)-monomethyl-L-arginine), as well as anti-IFN-gamma
      Abs, restored the ability of CD4(+) T cells to proliferate in vitro. Depletion of
      the F4/80(+) subset of Gr1(+) cells eliminated the suppressive activity of
      peritoneal exudate cells showing that these cells were macrophages. Thus, LNFPIII
      dextran rapidly expands the Gr1(+) suppressor macrophage population in the
      peritoneal cavities of otherwise naive mice. These Gr1(+) cells suppress
      proliferation of naive CD4(+) T cells in an NO-dependent mechanism, and may play
      a regulatory role in the switching of Th1- to Th2-type responses.

PMID- 11591753
TI  - betac cytokine receptor-induced stimulation of cAMP response element binding
      protein phosphorylation requires protein kinase C in myeloid cells: a novel
      cytokine signal transduction cascade.
AB  - We have recently shown that IL-3R occupancy activates a phosphatidylcholine
      specific phospholipase C, and the sustained diacylglycerol accumulation
      subsequently activates protein kinase C (PKC). In human IL-3-dependent myeloid
      cells (TF-1), the novel PKCepsilon isoform regulates bcl-2 expression and cell
      survival. The report of a PKC activatable cAMP response element (CRE) in the bcl
      2 promoter and a role for PKC in bcl-2 expression in B cells led us to the
      hypothesis that PKC phosphorylation activates transcription factor CREB after IL
      3R engagement. We found that IL-3 and GM-CSF induced phosphorylation of CREB on
      Ser(133) in TF-1 cells, and this phosphorylation was blocked by two structurally
      unrelated classes of PKC inhibitors. An inhibitor of cyclic nucleotide-dependent
      kinases did not block this phosphorylation. IL-4, which is biologically active in
      these cells but does not use the beta common subunit, did not phosphorylate CREB
      on Ser(133). Inhibition of mitogen-activated protein kinase kinase activity also
      inhibited IL3-induced CREB phosphorylation. The PKC inhibitors, but not a cyclic
      nucleotide-dependent kinase inhibitor, blocked IL-3 activation of CRE-dependent
      transcription from an egr-1 promoter/chloramphenicol acetyltransferase (CAT)
      reporter construction transiently transfected into TF-1 cells. Finally, TF-1
      cells stably overexpressing PKCepsilon, but not the delta isoform of PKC,
      enhanced CRE-dependent CAT expression from the promoter/reporter construction.
      Therefore, it is likely that a PKCepsilon kinase cascade resulting in CREB
      phosphorylation represents a novel signal transduction cascade for regulating
      cellular gene expression through the beta common cytokine receptor.

PMID- 11591754
TI  - CD4 promotes breadth in the TCR repertoire.
AB  - A diverse population of MHC class II-restricted CD4 lineage T cells develops in
      mice that lack expression of the CD4 molecule. In this study, we show that the
      TCR repertoire selected in the absence of CD4 is distinct, but still overlapping
      in its properties with that selected in the presence of CD4. Immunization of mice
      lacking CD4 caused the clonal expansion of T cells that showed less breadth in
      the range of Ag-binding properties exhibited by their TCRs. Specifically, the CD4
      deficient Ag-specific TCR repertoire was depleted of TCRs that demonstrated low
      affinity binding to their ligands. The data thus suggest a key role for CD4 in
      broadening the TCR repertoire by potentiating productive TCR signaling and clonal
      expansion in response to the engagement of low-affinity antigenic ligands.

PMID- 11591755
TI  - Enhanced immune responses in transgenic mice expressing a truncated form of the
      lymphocyte semaphorin CD100.
AB  - CD100/Sema4D is a 150-kDa transmembrane protein that belongs to the semaphorin
      family. Binding of CD100 to CD72 enhances the immune response by turning off the
      negative signaling effects of CD72. To investigate the physiological functions of
      CD100 in vivo, we generated transgenic mice expressing a truncated form of CD100.
      A large amount of the soluble form of CD100 was detected in the sera of mice
      expressing a truncated form of CD100, although the amount of CD100 was only
      slightly elevated on the surface of B cells. In the mutant mice the development
      of conventional B and T cells appeared normal in terms of the surface marker
      phenotypes, while the number of CD5(+) B-1 cells in the peritoneal cavity
      increased in comparison with wild-type mice. In vitro proliferation and Ig
      production of B cells in response to CD40 stimulation were considerably enhanced
      in mice expressing a truncated form of CD100. Additionally, in vivo both Ab
      responses against T cell-dependent Ags and generation of Ag-specific T cells were
      enhanced. Furthermore, introduction of the CD100-transgene could restore in vitro
      B cell responses as well as in vivo Ab production against T cell-dependent Ag in
      CD100-deficient mice. Collectively, these results not only indicate that CD100
      has an important role in the immune system, but also that the soluble form of
      CD100 released from the cell surface can exert functions in vivo.

PMID- 11591756
TI  - Overcoming the signaling defect of Lyn-sequestering, signal-curtailing
      FcepsilonRI dimers: aggregated dimers can dissociate from Lyn and form signaling
      complexes with Syk.
AB  - Clustering the tetrameric (alphabetagamma(2)) IgE receptor, FcepsilonRI, on
      basophils and mast cells activates the Src-family tyrosine kinase, Lyn, which
      phosphorylates FcepsilonRI beta and gamma subunit tyrosines, creating binding
      sites for the recruitment and activation of Syk. We reported previously that
      FcepsilonRI dimers formed by a particular anti-FcepsilonRI alpha mAb (H10)
      initiate signaling through Lyn activation and FcepsilonRI subunit
      phosphorylation, but cause only modest activation of Syk and little Ca(2+)
      mobilization and secretion. Curtailed signaling was linked to the formation of
      unusual, detergent-resistant complexes between Lyn and phosphorylated receptor
      subunits. Here, we show that H10-FcepsilonRI multimers, induced by adding
      F(ab')(2) of goat anti-mouse IgG to H10-treated cells, support strong Ca(2+)
      mobilization and secretion. Accompanying the recovery of signaling, H10
      FcepsilonRI multimers do not form stable complexes with Lyn and do support the
      phosphorylation of Syk and phospholipase Cgamma2. Immunogold electron microscopy
      showed that H10-FcepsilonRI dimers colocalize preferentially with Lyn and are
      rarely within the osmiophilic "signaling domains" that accumulate FcepsilonRI and
      Syk in Ag-treated cells. In contrast, H10-FcepsilonRI multimers frequently
      colocalize with Syk within osmiophilic patches. In sucrose gradient
      centrifugation analyses of detergent-extracted cells, H10-treated cells show a
      more complete redistribution of FcepsilonRI beta from heavy (detergent-soluble)
      to light (Lyn-enriched, detergent-resistant) fractions than cells activated with
      FcepsilonRI multimers. We hypothesize that restraints imposed by the particular
      orientation of H10-FcepsilonRI dimers traps them in signal-initiating Lyn
      microdomains, and that converting the dimers to multimers permits receptors to
      dissociate from Lyn and redistribute to separate membrane domains that support
      Syk-dependent signal propagation.

PMID- 11591757
TI  - Epitope mapping of the indirect T cell response to allogeneic class I MHC:
      sequences shared by donor and recipient MHC may prime T cells that provide help
      for alloantibody production.
AB  - Indirect allorecognition occurs when T cells recognize donor MHC presented as
      peptide epitopes by recipient APC, but the precise nature of the epitopes
      involved remains unclear. Rejection of rat MHC class I-disparate PVG.R8
      (RT1.A(a)) grafts by PVG.RT1(u) (RT1.A(u)) recipients is mediated by indirectly
      restricted CD4 T cells that provide help for the generation of alloantibody. In
      this study, epitope mapping was performed using a functionally relevant readout
      (alloantibody production) to identify key peptides that prime an indirect
      alloimmune response, leading to graft rejection. PVG.RT1(u) rats were immunized
      with a series of overlapping 15-mer peptides (peptides 1-18) that spanned the
      alpha1 and alpha2 domains of the RT1.A(a) molecule. Several peptides were able to
      accelerate both the alloantibody response to the intact RT1.A(a) Ag and PVG.R8
      heart graft rejection. An immunodominant epitope was identified within the
      hypervariable region of the alpha1 domain. Fine mapping of this region with a
      second series of peptides overlapping by single amino acids confirmed the
      presence of an eight-amino acid core determinant. Additional "subdominant"
      epitopes were identified, two of which were located within regions of amino acid
      homology between the RT1.A(a) and RT1.A(u) molecules and not, as had been
      expected, within other hypervariable regions. The contribution of self-epitopes
      to indirect allorecognition was emphasized by the demonstration that i.v.
      administration of a 15-mer peptide encompassing one of the subdominant self
      determinants diminished the recipient's ability to mount an alloantibody response
      on challenge with intact A(a) alloantigen. Our findings suggest that cryptic self
      epitopes recognized by autoreactive T cells may contribute to allograft rejection
      and should be considered when designing novel strategies for inducing tolerance
      to alloantigen.

PMID- 11591758
TI  - Cytokines regulate the capacity of CD8alpha(+) and CD8alpha(-) dendritic cells to
      prime Th1/Th2 cells in vivo.
AB  - Prior studies have shown that subclasses of dendritic cells (DC) direct the
      development of distinct Th populations in rodents and in humans. In the mouse, we
      have recently shown that administration of Ag-pulsed CD8alpha(-) DC induces a Th2
      type response, whereas injection of CD8alpha(+) DC leads to Th1 differentiation.
      To define the DC-derived factors involved in the polarization of Th responses, we
      injected either subset purified from mice genetically deficient for IFN-gamma, IL
      4, IL-12, or IL-10 into wild-type animals. In this work, we report that DC
      derived IL-12 and IFN-gamma are required for Th1 priming by CD8alpha(+) DC,
      whereas IL-10 is required for optimal development of Th2 cells by CD8alpha(-) DC.
      The level of IL-12 produced by the DC appears to determine the Th1/Th2 balance in
      vivo. We further show that the function of DC subsets displays some flexibility.
      Treatment of DC with IL-10 in vitro induces a selective decrease in the viability
      of CD8alpha(+) DC. Conversely, incubation with IFN-gamma down-regulates the Th2
      promoting capacities of CD8alpha(-) DC and increases the Th1-skewing properties
      of both subsets.

PMID- 11591759
TI  - Impaired activation of islet-reactive CD4 T cells in pancreatic lymph nodes of B
      cell-deficient nonobese diabetic mice.
AB  - Despite the impressive protection of B cell-deficient (muMT(-/-)) nonobese
      diabetic (NOD) mice from spontaneous diabetes, existence of mild pancreatic islet
      inflammation in these mice indicates that initial autoimmune targeting of beta
      cells has occurred. Furthermore, muMT(-/-) NOD mice are shown to harbor a latent
      repertoire of diabetogenic T cells, as evidenced by their susceptibility to
      cyclophosphamide-induced diabetes. The quiescence of this pool of islet-reactive
      T cells may be a consequence of impaired activation of T lymphocytes in B cell
      deficient NOD mice. In this regard, in vitro anti-CD3-mediated stimulation
      demonstrates impaired activation of lymph node CD4 T cells in muMT(-/-) NOD mice
      as compared with that of wild-type counterparts, a deficiency that is correlated
      with an exaggerated CD4 T cell:APC ratio in lymph nodes of muMT(-/-) NOD mice.
      This feature points to an insufficient availability of APC costimulation on a per
      T cell basis, resulting in impaired CD4 T cell activation in lymph nodes of muMT(
      /-) NOD mice. In accordance with these findings, an islet-reactive CD4 T cell
      clonotype undergoes suboptimal activation in pancreatic lymph nodes of muMT(-/-)
      NOD recipients. Overall, the present study indicates that B cells in the
      pancreatic lymph node microenvironment are critical in overcoming a checkpoint
      involving the provision of optimal costimulation to islet-reactive NOD CD4 T
      cells.

PMID- 11591760
TI  - Spatial organization of signal transduction molecules in the NK cell immune
      synapses during MHC class I-regulated noncytolytic and cytolytic interactions.
AB  - The cytolytic activity of NK cells is tightly regulated by inhibitory receptors
      specific for MHC class I Ags. We have investigated the composition of signal
      transduction molecules in the supramolecular activation clusters in the MHC class
      I-regulated cytolytic and noncytolytic NK cell immune synapses. KIR2DL3-positive
      NK clones that are specifically inhibited in their cytotoxicity by HLA-Cw*0304
      and polyclonal human NK cells were used for conjugate formation with target cells
      that are either protected or are susceptible to NK cell-mediated cytotoxicity.
      Polarization of talin, microtubule-organizing center, and lysosomes occurred only
      during cytolytic interactions. The NK immune synapses were analyzed by three
      dimensional immunofluorescence microscopy, which showed two distinctly different
      synaptic organizations in NK cells during cytolytic and noncytolytic
      interactions. The center of a cytolytic synapse with MHC class I-deficient target
      is comprised of a complex of signaling molecules including Src homology (SH)2
      containing protein tyrosine phosphatase-1 (SHP-1). Closely related molecules with
      overlapping functions, such as the Syk kinases, SYK, and ZAP-70, and adaptor
      molecules, SH2 domain-containing leukocyte protein of 76 kDa and B cell linker
      protein, are expressed in activated NK cells and are all recruited to the center
      of the cytolytic synapse. In contrast, the noncytolytic synapse contains SHP-1,
      but is lacking other components of the central supramolecular activation cluster.
      These findings indicate a functional role for SHP-1 in both the cytolytic and
      noncytolytic interactions. We also demonstrate, in three-cell conjugates, that a
      single NK cell forms a cytolytic synapse with a susceptible target cell in the
      presence of both susceptible and nonsusceptible target cells.

PMID- 11591761
TI  - Protection from pulmonary fibrosis in the absence of CCR2 signaling.
AB  - Pulmonary fibrosis can be modeled in animals by intratracheal instillation of
      FITC, which results in acute lung injury, inflammation, and extracellular matrix
      deposition. We have previously shown that despite chronic inflammation, this
      model of pulmonary fibrosis is lymphocyte independent. The CC chemokine monocyte
      chemoattractant protein-1 is induced following FITC deposition. Therefore, we
      have investigated the contribution of the main monocyte-chemoattractant protein-1
      chemokine receptor, CCR2, to the fibrotic disease process. We demonstrate that
      CCR2(-/-) mice are protected from fibrosis in both the FITC and bleomycin
      pulmonary fibrosis models. The protection is specific for the absence of CCR2, as
      CCR5(-/-) mice are not protected. The protection is not explained by differences
      in acute lung injury, or the magnitude or composition of inflammatory cells. FITC
      treated CCR2(-/-) mice display differential patterns of cellular activation as
      evidenced by the altered production of cytokines and growth factors following
      FITC inoculation compared with wild-type controls. CCR2(-/-) mice have increased
      levels of GM-CSF and reduced levels of TNF-alpha compared with FITC-treated
      CCR2(+/+) mice. Thus, CCR2 signaling promotes a profibrotic cytokine cascade
      following FITC administration.

PMID- 11591762
TI  - Endothelial cell costimulation of T cell activation through CD58-CD2 interactions
      involves lipid raft aggregation.
AB  - Human endothelial cells (EC) costimulate CD4(+) memory T cell activation through
      CD58-CD2 interactions. In this study we tested the hypothesis that EC activate
      distinct costimulatory pathways in T cells that target specific transcription
      factors. AP-1, composed of fos and jun proteins, is a critical effector of TCR
      signaling and binds several sites in the IL-2 promoter. EC augment c-fos promoter
      activity in T cells; however, deletion analysis reveals no transcription factor
      binding sites in the promoter uniquely responsive to EC costimulation.
      Overexpression of AP-1 proteins in T cells augments the activity of an AP-1
      luciferase reporter gene equally in the absence or the presence of EC
      costimulation. Interestingly, EC stimulate a similar 2- to 3-fold up-regulation
      of AP-1, NF-AT, NF-kappaB, and NF-IL-2-luciferase reporters. CD2 mAbs completely
      block EC effects on all of these pathways, as well as costimulation of IL-2
      secretion. We conclude that EC costimulation through CD2 does not trigger a
      single distinct costimulatory pathway in T cells, but rather, it amplifies
      several pathways downstream of the TCR. Indeed, we find that early EC
      costimulation acts "upstream" of the TCR by promoting lipid raft aggregation,
      thus amplifying TCR signaling. Soluble CD2 mAbs block EC-induced raft
      aggregation, whereas cross-linking CD2 promotes aggregation. These data are
      consistent with the critical role of CD2 in organizing the T cell-APC contact
      zone.

PMID- 11591763
TI  - Rudimentary TCR signaling triggers default IL-10 secretion by human Th1 cells.
AB  - Understanding the process of inducing T cell activation has been hampered by the
      complex interactions between APC and inflammatory Th1 cells. To dissociate Ag
      specific signaling through the TCR from costimulatory signaling, rTCR ligands
      (RTL) containing the alpha1 and beta1 domains of HLA-DR2b (DRA*0101:DRB1*1501)
      covalently linked with either the myelin basic protein peptide 85-99 (RTL303) or
      CABL-b3a2 (RTL311) peptides were constructed to provide a minimal ligand for
      peptide-specific TCRs. When incubated with peptide-specific Th1 cell clones in
      the absence of APC or costimulatory molecules, only the cognate RTL induced
      partial activation through the TCR. This partial activation included rapid TCR
      zeta-chain phosphorylation, calcium mobilization, and reduced extracellular
      signal-related kinase activity, as well as IL-10 production, but not
      proliferation or other obvious phenotypic changes. On restimulation with
      APC/peptide, the RTL-pretreated Th1 clones had reduced proliferation and secreted
      less IFN-gamma; IL-10 production persisted. These findings reveal for the first
      time the rudimentary signaling pattern delivered by initial engagement of the
      external TCR interface, which is further supplemented by coactivation molecules.
      Activation with RTLs provides a novel strategy for generating autoantigen
      specific bystander suppression useful for treatment of complex autoimmune
      diseases.

PMID- 11591764
TI  - Immunobiological analysis of TCR single-chain transgenic mice reveals new
      possibilities for interaction between CDR3alpha and an antigenic peptide bound to
      MHC class I.
AB  - The interaction between TCRs and peptides presented by MHC molecules determines
      the specificity of the T cell-mediated immune response. To elucidate the
      biologically important structural features of this interaction, we generated TCR
      beta-chain transgenic mice using a TCR derived from a T cell clone specific for
      the immunodominant peptide of vesicular stomatitis virus (RGYVYQGL, VSV8)
      presented by H-2K(b). We immunized these mice with VSV8 or analogs substituted at
      TCR contact residues (positions 1, 4, and 6) and analyzed the CDR3alpha sequences
      of the elicited T cells. In VSV8-specific CTLs, we observed a highly conserved
      residue at position 93 of CDR3alpha and preferred Jalpha usage, indicating that
      multiple residues of CDR3alpha are critical for recognition of the peptide.
      Certain substitutions at peptide position 4 induced changes at position 93 and in
      Jalpha usage, suggesting a potential interaction between CDR3alpha and position
      4. Cross-reactivity data revealed the foremost importance of the Jalpha region in
      determining Ag specificity. Surprisingly, substitution at position 6 of VSV8 to a
      negatively charged residue induced a change at position 93 of CDR3alpha to a
      positively charged residue, suggesting that CDR3alpha may interact with position
      6 in certain circumstances. Analogous interactions between the TCR alpha-chain
      and residues in the C-terminal half of the peptide have not yet been revealed by
      the limited number of TCR/peptide-MHC crystal structures reported to date. The
      transgenic mouse approach allows hundreds of TCR/peptide-MHC interactions to be
      examined comparatively easily, thus permitting a wide-ranging analysis of the
      possibilities for Ag recognition in vivo.

PMID- 11591765
TI  - CXCR3 expression on CD34(+) hemopoietic progenitors induced by granulocyte
      macrophage colony-stimulating factor: II. Signaling pathways involved.
AB  - CXCR3, known to have four ligands (IFN-gamma inducible protein 10 (gamma IP-10),
      monokine induced by IFN-gamma (Mig), I-TAC, and 6Ckine), is predominantly
      expressed on memory/activated T lymphocytes. We recently reported that GM-CSF
      induces CXCR3 expression on CD34(+) hemopoietic progenitors, in which gamma IP-10
      and Mig induce chemotaxis and adhesion. Here we further report that stimulation
      with GM-CSF causes phosphorylation of Syk protein kinase, but neither Casitas B
      lineage lymphoma (Cbl) nor Cbl-b in CD34(+) hemopoietic progenitors can be
      blocked by anti-CD116 mAb. Specific Syk blocking generated by PNA antisense
      completely inhibits GM-CSF-induced CXCR3 expression in CD34(+) progenitors at
      both mRNA and protein as well as at functional levels (chemotaxis and adhesion).
      Cbl and Cbl-b blocking have no such effects. Thus, GM-CSF binds to its receptor
      CD116, and consequently activates Syk phosphorylation, which leads to induce
      CXCR3 expression. gamma IP-10 and Mig can induce Syk, Cbl, and Cbl-b
      phosphorylation in CD34(+) progenitors by means of CXCR3. gamma IP-10 or Mig has
      induced neither chemotaxis nor adhesion in GM-CSF-stimulated Cbl-b-blocked
      CD34(+) hemopoietic progenitors, whereas SDF-1alpha induces both chemotaxis and
      adhesion in these cells. Interestingly, gamma IP-10 and Mig can induce chemotaxis
      and adhesion in GM-CSF-stimulated Syk- or Cbl-blocked CD34(+) hemopoietic
      progenitors. Thus, Cbl-b, but not Syk and Cbl phosphorylation, is essential for
      gamma IP-10- and Mig-induced chemotaxis and adhesion in CD34(+) hemopoietic
      progenitors. This study provides a useful insight into novel signaling
      transduction pathways of the functions of CXCR3/gamma IP-10 and Mig, which may be
      especially important in the cytokine/chemokine environment for mobilization,
      homing, and recruitment during proliferation, differentiation, and maturation of
      hemopoietic progenitor cells.

PMID- 11591766
TI  - The cell type-specific expression of the murine IL-13 gene is regulated by GATA
      3.
AB  - IL-13, a Th2 cell-specific cytokine, is a major effector molecule mediating
      several pathological features of allergic asthma. However, the transcriptional
      regulation of the IL-13 gene remains unclear. Here we demonstrate, by using
      intracellular cytokine staining, that IL-13 is not always coexpressed with other
      Th2 cytokines in normal Th cells on a single cell basis. In addition, we
      identified and cloned a minimal inducible and cell type-specific promoter of the
      murine IL-13 gene. The cell type specificity of the minimal IL-13 promoter is
      mediated by a functionally critical GATA-3 site that binds endogenous GATA-3
      proteins, whereas the induction by PMA/ionomycin is mediated by distinct cis
      acting elements. Furthermore, by expressing GATA-3 in wild-type and c-maf
      transgenic Th1 cells, we demonstrate that the expression of IL-13 is regulated by
      a mechanism distinct from that regulating the expression of IL-4, and that the
      expression of Th1 and Th2 cytokine genes does not have to be mutually exclusive
      in effector Th cells.

PMID- 11591767
TI  - Unique function for carboxyl-terminal domain of Oct-2 in Ig-secreting cells.
AB  - The activity of Ig gene promoters and enhancers is regulated by two related
      transcription factors, Oct-1 (ubiquitous) and Oct-2 (B lineage specific), which
      bind the octamer motif (ATTTGCAT) present in these elements. As Ig promoter
      binding factors, Oct-1 and Oct-2 each work together with a B lymphocyte-specific
      cofactor OCA-B/OBF-1/Bob-1 that interacts with them through their POU (DNA
      binding) domains. Because both can mediate Ig promoter activity in B cells, there
      has been some question as to whether these two octamer-binding factors serve
      distinct functions in lymphocytes. We have shown previously that the silencing of
      B lymphocyte-specific genes in plasmacytoma x T lymphoma hybrids can be prevented
      by preserving Oct-2 expression. The pronounced effect of this transcription
      factor on the phenotype of plasmacytoma x T lymphoma hybrids established a
      critical role for Oct-2 not only in maintaining Ig gene expression, but in
      maintaining the overall genetic program of Ig-secreting cells. In the present
      study, we have explored the functional differences between Oct-1 and Oct-2 using
      chimeric Oct-1/Oct-2 proteins in cell fusion assays. Our results provide further
      evidence for an essential role for Oct-2 in Ig-secreting cells and identify the C
      terminal domain of Oct-2 as responsible for its unique function in these cells.

PMID- 11591768
TI  - Identification of a novel cytokine, ML-1, and its expression in subjects with
      asthma.
AB  - A novel gene, designated ML-1, was identified from a human genomic DNA clone and
      human T cell cDNA sequences. The second exon of ML-1 gene shares significant
      sequence identity with the gene encoding IL-17 (IL-17). ML-1 gene expression was
      up-regulated in activated PBMCs, CD4(+) T cells, allergen-specific Th0, Th1, and
      Th2 clones, activated basophils, and mast cells. Increased expression of the ML-1
      gene, but not IL-17, was seen following allergen challenge in four asthmatic
      subjects, suggesting its role in allergic inflammatory responses. ML-1 from
      transiently transfected COS-7 cells was able to induce gene expression and
      protein production for IL-6 and IL-8 (at 10 ng/ml of ML-1: for IL-6, 599.6 +/-
      19.1 pg/ml; for IL-8, 1724.2 +/- 132.9 pg/ml; and at 100 ng/ml of ML-1: for IL-6,
      1005.3 +/- 55.6 pg/ml; for IL-8, 4371.4 +/- 280.5 pg/ml; p < 0.05 for both doses
      vs baseline) in primary bronchial epithelial (PBE) cells. Furthermore, increased
      expression of ICAM-1 was found in ML-1-stimulated PBE cells (mean fluorescence
      intensity (MFI) = 31.42 +/- 4.39 vs baseline, MFI = 12.26 +/- 1.77, p < 0.05), a
      functional feature distinct from IL-17 (MFI = 11.07 +/- 1.22). This effect was
      not inhibited by a saturating amount of IL-17. These findings demonstrate that ML
      1 is a novel cytokine with a distinct function, and suggest a different receptor
      for ML-1 on PBE cells.

PMID- 11591769
TI  - IL-10 inhibits apoptosis of promyeloid cells by activating insulin receptor
      substrate-2 and phosphatidylinositol 3'-kinase.
AB  - IL-10 is well known to be a potent inhibitor of the synthesis of proinflammatory
      cytokines, but noninflammatory hemopoietic cells also express IL-10Rs. Here we
      show that IL-10 directly affects progenitor myeloid cells by protecting them from
      death following the removal of growth factors. Murine factor-dependent cell
      progenitors cultured in the absence of growth factors were 43 +/- 1% apoptotic
      after 12 h. Addition of IL-10 at a concentration as low as 100 pg/ml
      significantly reduced the apoptotic population to 32 +/- 3%. At 10 ng/ml, IL-10
      caused a 4-fold reduction in the apoptotic population (11 +/- 1%). The anti
      apoptotic activity of IL-10 was significantly inhibited with a neutralizing IL
      10R Ab. Factor-dependent cell progenitor promyeloid cells expressed functional IL
      10Rs, as assessed by precipitation of a 110-kDa protein with an Ab to the IL-10R
      and by the ability of IL-10 to activate Jak1 and Tyk2 and to phosphorylate
      tyrosine 705 on Stat-3. IL-10 increased tyrosyl phosphorylation of insulin
      receptor substrate-2 and stimulated the enzymatic activity of both
      phosphatidylinositol 3'-kinase and Akt. The anti-apoptotic activity of IL-10 was
      blocked by inhibition of phosphatidylinositol 3'-kinase. Wortmannin and LY294002
      also totally inhibited activation of extracellular signal-related kinase (ERK)1/2
      by IL-10. Direct inhibition of ERK1/2 with the mitogen-activated protein
      kinase/ERK kinase inhibitor PD98059 partially, but significantly, impaired the
      anti-apoptotic activity of IL-10. These data establish that activation of the IL
      10R promotes survival of progenitor myeloid cells. This survival-promoting
      activity is totally due to IL-10 stimulating the insulin receptor substrate-2/PI
      3-kinase/Akt pathway, which increases the anti-apoptotic activity of ERK1/2.

PMID- 11591770
TI  - A region of tapasin that affects L(d) binding and assembly.
AB  - Tapasin has been shown to stabilize TAP and to link TAP to the MHC class I H
      chain. Evidence also has been presented that tapasin influences the loading of
      peptides onto MHC class I. To explore the relationship between the ability of
      tapasin to bind to TAP and the MHC class I H chain and the ability of tapasin to
      facilitate class I assembly, we have created novel tapasin mutants and expressed
      them in 721.220-L(d) cells. One mutant has a deletion of nine amino acid residues
      (tapasin Delta334-342), and the other has amino acid substitutions at positions
      334 and 335. In this report we describe the ability of these mutants to interact
      with L(d) and their effects on L(d) surface expression. We found that tapasin
      Delta334-342 was unable to bind to the L(d) H chain, and yet it facilitated L(d)
      assembly and expression. Tapasin Delta334-342 was able to bind and stabilize TAP,
      suggesting that TAP stabilization may be important to the assembly of L(d).
      Tapasin mutant H334F/H335Y, unlike tapasin Delta334-342, bound to L(d).
      Expression of tapasin H334F/H335Y in 721.220-L(d) reduced the proportion of cell
      surface open forms of L(d) and retarded the migration of L(d) from the
      endoplasmic reticulum. In total, our results indicate that the 334-342 region of
      tapasin influences L(d) assembly and transport.

PMID- 11591771
TI  - Differential evolution and stability of epitope-specific CD8(+) T cell responses
      in EBV infection.
AB  - Murine models of lymphocytic choriomeningitis virus infection suggest that the
      memory CD8(+) T cell repertoire is reflective of the CD8(+) T cell repertoire
      generated during acute infection. Less is known regarding the evolution of CD8(+)
      T cell repertoires during human viral infections. We therefore examined epitope
      specific CD8(+) T cell responses in a large cohort of individuals with acute
      through latent Epstein-Barr virus infection. Using 16 of 20 published EBV
      epitopes restricted by HLA-A2, HLA-A3 or HLA-B7, we showed that lytic cycle
      specific CD8(+) T cell responses predominated during acute EBV infection.
      However, whereas HLA-A2(+)-restricted BMLF-1-specific CD8(+) T cell responses
      were maintained through latency, HLA-A2(+)- and HLA-B7(+)-restricted BZLF-1, as
      well as HLA-A3(+)-restricted BRLF-1 CD8(+) T cell responses, were generated but
      not readily maintained. Analyses of CD8(+) T cell responses to EBV latent cycle
      Ags showed delayed detection and lower frequencies of latent epitope-specific
      CD8(+) T cell responses during acute EBV infection, with maintenance of these
      responses 1 yr post-EBV infection. Early BMLF-1 and EBNA-3A epitope-specific
      CD8(+) T cell frequencies did not correlate with their frequencies at 1 yr
      postinfection. Interestingly, populations of EBV-specific CD8(+) T cells were
      stable during 20 mo in our long term EBV-seropositive populations, suggesting
      homeostasis between virus and the host immune system. This study demonstrates
      that CD8(+) T cell repertoires generated during persistent viral infections are
      not simply reflective of the initial pool of CD8(+) T cells and provides evidence
      that the generation of CD8(+) T cell responses to a persistent infection is a
      dynamic process.

PMID- 11591772
TI  - Notch-1 regulates NF-kappaB activity in hemopoietic progenitor cells.
AB  - We investigated the interaction between two elements critical for differentiation
      of hemopoietic cells, the Notch-1 receptor and the transcription factor NF
      kappaB. These factors were studied in hemopoietic progenitor cells (HPC) using
      Notch-1 antisense transgenic (Notch-AS-Tg) mice. DNA binding of NF-kappaB as well
      as its ability to activate transcription was strongly decreased in HPC from Notch
      AS-Tg mice. NF-kappaB-driven transcriptional activity was completely restored
      after transduction of the cells with retroviral constructs containing activated
      Notch-1 gene. HPC from Notch-AS-Tg mice have decreased levels of several members
      of the NF-kappaB family, p65, p50, RelB, and c-Rel and this is due to down
      regulation of the gene expression. To investigate functional consequences of
      decreased NF-kappaB activity in transgenic mice, we studied LPS-induced
      proliferation of B cells and GM-CSF-dependent differentiation of dendritic cells
      from HPC. These two processes are known to be closely dependent on NF-kappaB. B
      cells from Notch-AS-Tg mice had almost 3-fold lower response to LPS than B cells
      isolated from control mice. Differentiation of dendritic cells was significantly
      affected in Notch-AS-Tg mice. However, it was restored by transduction of
      activated Notch-1 into HPC. Taken together, these data indicate that in HPC NF
      kappaB activity is regulated by Notch-1 via transcriptional control of NF-kappaB.

PMID- 11591773
TI  - Enforced expression of GATA-3 severely reduces human thymic cellularity.
AB  - Following bone marrow transplantation, patients often suffer from immune
      incompetence by reduced or late T cell development. Moreover, adult bone marrow
      stem cells have a lower capacity to generate T cells compared with fetal liver-
      and umbilical cord blood-derived progenitors. Therefore, enhancing thymic
      dependent T cell generation might hold great therapeutic potential. GATA-3 is a
      transcription factor that is essential in T cell development. In this study we
      examined the therapeutic potential of GATA-3 to enhance T cell generation by
      overexpressing GATA-3 in T cell progenitors followed by fetal thymic organ
      culture (FTOC). We observed that early during FTOC, there was an enhanced
      differentiation toward the double positive stage of T cell development. From day
      10 of FTOC, however, overexpression of GATA-3 induced a severe reduction in
      thymic cellularity, which probably correlates with the absence of a functional
      TCR-beta chain. We further show that the frequency of apoptosis was increased in
      GATA-3-transduced thymocytes. Despite the absence of a functional TCR-beta chain,
      GATA-3 transduced progenitors were able to differentiate into CD8beta(+) double
      positive thymocytes. This study shows that a strictly regulated expression of
      GATA-3 is essential for normal T cell development and this puts severe
      restrictions on the potential therapeutic use of continuously overexpressed GATA
      3.

PMID- 11591774
TI  - IL-12, STAT4-dependent up-regulation of CD4(+) T cell core 2 beta-1,6-n
      acetylglucosaminyltransferase, an enzyme essential for biosynthesis of P-selectin
      ligands.
AB  - TCR activation of naive T cells in the presence of IL-12 drives polarization
      toward a Th1 phenotype and synthesis of P- and E-selectin ligands.
      Fucosyltransferase VII (Fuc-T VII) and core 2 beta-1,6-N
      acetylglucosaminyltransferase (C2GnT) are critical for biosynthesis of selectin
      ligands. P-selectin glycoprotein ligand-1 is the best characterized ligand for P
      selectin and also binds E-selectin. The contributions of TCR and cytokine
      signaling pathways to up-regulate Fuc-T VII and C2GnT during biosynthesis of E-
      and P-selectin ligands, such as P-selectin glycoprotein ligand 1, are unknown. IL
      12 signals via the STAT4 pathway. Here, naive DO11.10 TCR transgenic and STAT4(-/
      ) TCR transgenic CD4(+) T cells were stimulated with Ag and IL-12 (Th1
      condition), IL-4 (Th2), or neutralizing anti-IL-4 mAb only (Th0). The levels of
      Fuc-T VII and C2GnT mRNA in these cells were compared with their adhesive
      interactions with P- and E-selectin in vitro under flow. The data show IL
      12/STAT4 signaling is necessary for induction of C2GnT, but not Fuc-TVII mRNA,
      and that STAT4(-/-) Th1 cells do not traffic normally to sites of inflammation in
      vivo, do not interact with P-selectin, and exhibit a partial reduction of E
      selectin interactions under shear stress in vitro. Ag-specific TCR activation in
      CD4(+) T cells was sufficient to trigger induction of Fuc-TVII, but not C2GnT,
      mRNA and expression of E-selectin, but not P-selectin, ligands. Thus, Fuc-T VII
      and C2GnT are regulated by different signals during Th cell differentiation, and
      both cytokine and TCR signals are necessary for the expression of E- and P
      selectin ligands.

PMID- 11591775
TI  - TCRA gene rearrangement in immature thymocytes in absence of CD3, pre-TCR, and
      TCR signaling.
AB  - During thymocyte differentiation, TCRA genes are massively rearranged only after
      productively rearranged TCRB genes are expressed in association with pTalpha and
      CD3 complex molecules within a pre-TCR. Signaling from the pre-TCR via the CD3
      complex is thought to be required to promote TCRA gene accessibility and
      recombination. However, alphabeta(+) thymocytes do develop in pTalpha-deficient
      mice, showing that TCRalpha-chain genes are rearranged, either in CD4(-)CD8(-) or
      CD4(+)CD8(+) thymocytes, in the absence of pre-TCR expression. In this study, we
      analyzed the TCRA gene recombination status of early immature thymocytes in
      mutant mice with arrested thymocyte development, deficient for either CD3 or
      pTalpha and gammac expression. ADV genes belonging to different families were
      found rearranged to multiple AJ segments in both cases. Thus, TCRA gene
      rearrangement is independent of CD3 and gammac signaling. However, CD3 expression
      was found to play a role in transcription of rearranged TCRalpha-chain genes in
      CD4(-)CD8(-) thymocytes. Taken together, these results provide new insights into
      the molecular control of early T cell differentiation.

PMID- 11591776
TI  - Chromatin remodeling, measured by a novel real-time polymerase chain reaction
      assay, across the proximal promoter region of the IL-2 gene.
AB  - The structure of chromatin and its remodeling following activation are important
      aspects of the control of inducible gene transcription. The IL-2 gene is induced
      in a cell specific-manner in T cells following an antigenic stimulus. We show,
      using a novel real-time PCR assay, that significant chromatin remodeling of the
      IL-2 proximal promoter region occurred upon stimulation of both the murine EL-4 T
      cell line and primary CD4(+) T cells. Chromatin remodeling appears to be limited
      to the first 300 bp of the proximal promoter region as measured by micrococcal
      nuclease and restriction enzyme accessibility. Time course studies indicated that
      chromatin remodeling was observed at 1.5 h postinduction and was maintained for
      up to 16 h. The remodeling is reversible upon removal of the stimulus. The region
      immediately upstream from the transcription start site, however, remains
      accessible for up to 16 h. Upon restimulation, remodeling occurs much more
      rapidly, consistent with a more rapid rise in IL-2 mRNA levels. Using a number of
      pharmacological inhibitors we show that remodeling is dependent on the presence
      of specific transcription factors, but not on the modification of histones. The
      development of this novel chromatin accessibility assay based on real-time PCR
      has allowed rapid, sensitive, and quantitative measurements on the IL-2 gene
      following cellular activation in both T cell lines and primary cells.

PMID- 11591777
TI  - An ancient lectin-dependent complement system in an ascidian: novel lectin
      isolated from the plasma of the solitary ascidian, Halocynthia roretzi.
AB  - Mannose-binding lectin (MBL) is a C-type lectin involved in the first line of
      host defense against pathogens and it requires MBL-associated serine protease
      (MASP) for activation of the complement lectin pathway. To elucidate the origin
      and evolution of MBL, MBL-like lectin was isolated from the plasma of a
      urochordate, the solitary ascidian Halocynthia roretzi, using affinity
      chromatography on a yeast mannan-Sepharose. SDS-PAGE of the eluted proteins
      revealed a major band of approximately 36 kDa (p36). p36 cDNA was cloned from an
      ascidian hepatopancreas cDNA library. Sequence analysis revealed that the carboxy
      terminal half of the ascidian lectin contains a carbohydrate recognition domain
      (CRD) that is homologous to C-type lectin, but it lacks a collagen-like domain
      that is present in mammalian MBLs. Purified p36 binds specifically to glucose but
      not to mannose or N-acetylglucosamine, and it was designated glucose-binding
      lectin (GBL). The two ascidian MASPs associated with GBL activate ascidian C3,
      which had been reported to act as an opsonin. The removal of GBL-MASPs complex
      from ascidian plasma using Ab against GBL inhibits C3-dependent phagocytosis.
      These observations strongly suggest that GBL acts as a recognition molecule and
      that the primitive complement system, consisting of the lectin-proteases complex
      and C3, played a major role in innate immunity before the evolution of an
      adaptive immune system in vertebrates.

PMID- 11591778
TI  - IL-2 during in vitro priming promotes subsequent engraftment and successful
      adoptive tumor immunotherapy by persistent memory phenotypic CD8(+) T cells.
AB  - Adoptive T cell tumor immunotherapy potentially consists of two protective
      components by the transferred effector cells, the immediate immune response and
      the subsequent development of memory T cells. The extent by which adoptively
      transferred CD8(+) CTL are destined to become memory T cells is ambiguous as most
      studies focus on the acute effects on tumor shortly following adoptive transfer.
      In this study we show that a substantial fraction of the input CTL develop into
      memory cells that reject a s.c. tumor challenge. The use of exogenous IL-2 or a
      combination of IL-2 and IL-4, but not solely IL-4, during the ex vivo culture for
      the CTL inoculation was necessary for efficient development of CD8(+) memory T
      cells. Thus, an important component of adoptive immunotherapy using CTL is the
      production of CD8(+) Ag-specific memory cells which is primarily favored by IL-2
      receptor signaling during ex vivo generation of the effector CTL.

PMID- 11591779
TI  - The pulmonary environment promotes Th2 cell responses after nasal-pulmonary
      immunization with antigen alone, but Th1 responses are induced during instances
      of intense immune stimulation.
AB  - The purpose of this study was to determine the nature of the CD4(+) Th cell
      responses induced after nasal-pulmonary immunization, especially those coinciding
      with previously described pulmonary inflammation associated with the use of the
      mucosal adjuvant, cholera toxin (CT). The major T cell population in the lungs of
      naive mice was CD4(+), and these cells were shown to be predominantly of Th2 type
      as in vitro polyclonal stimulation resulted in IL-4, but not IFN-gamma,
      production. After nasal immunization with influenza Ag alone, Th2 cytokine mRNA
      (IL-4 and IL-5) levels were increased, whereas there was no change in Th1
      cytokine (IL-2 and IFN-gamma) mRNA expression. The use of the mucosal adjuvant,
      CT, markedly enhanced pulmonary Th2-type responses; however, there was also a Th1
      component to the T cell response. Using in vitro Ag stimulation of pulmonary
      lymphocytes, influenza virus-specific cytokine production correlated with the
      mRNA cytokine results. Furthermore, there was a large increase in CD4(+) Th cell
      numbers in lungs after nasal immunization using CT, correlating with the
      pulmonary inflammatory infiltrate previously described. Coincidentally, both
      macrophage-inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta mRNA expression
      increased in the lungs after immunization with Ag plus CT, while only MIP-1beta
      expression increased when mice were given influenza Ag alone. Our study suggests
      a mechanism to foster Th1 cell recruitment into the lung, which may impact on
      pulmonary immune responses. Thus, while Th2 cell responses may be prevalent in
      modulating mucosal immunity in the lungs, Th1 cell responses contribute to
      pulmonary defenses during instances of intense immune stimulation.

PMID- 11591780
TI  - Immunoendocrine interactions during chronic cysticercosis determine male mouse
      feminization: role of IL-6.
AB  - Taenia crassiceps cysticercosis results in an impressive feminization in male
      mice during chronic infection, characterized by increased serum estradiol levels
      100 times their normal values, while those of testosterone and
      dihydrotestosterone are decreased by 85 and 95% respectively. Concomitantly, the
      levels of follicle-stimulating hormone and IL-6 are increased 70 and 90 times
      their normal values in the infected male mice. Since a specific Th1/Th2 shift of
      the immune response has been previously reported during the chronic infection,
      and this shift may be associated with the feminization process, we proposed that
      this shift is induced by immunoendocrine interactions during the disease, and
      this gives way to a change in the initial resistance to the infection in the male
      mice, which become as susceptible as female mice. To confirm this hypothesis, we
      depleted immune system activity in two different ways: total body irradiation and
      neonatal thymectomy. Our results show that when immune system activity is
      depleted using either strategy, the male mice do not feminize, and the levels of
      follicle-stimulating hormone and IL-6 are inhibited. Depletion of IL-6 using IL
      6(-/-) knockout mice does not produce the feminization process stated above,
      while restitution of the IL-6(-/-) knockout, irradiated, and thymectomized mice
      with murine recombinant IL-6 restores the feminization process. Expression of the
      IL-6 gene was found only in the testes and spleen of infected animals. Our
      results illustrate the importance of immunoendocrine interactions during a
      parasitic disease and show a possible new mechanism of parasite establishment in
      an initially resistant host.

PMID- 11591781
TI  - Leishmania amazonensis-dendritic cell interactions in vitro and the priming of
      parasite-specific CD4(+) T cells in vivo.
AB  - The progressive disease following Leishmania amazonensis infection in mice
      requires functional CD4(+) T cells, which are primed to a disease-promoting
      phenotype during the infection. To understand how these pathogenic T cells are
      generated and the role of dendritic cells (DCs) in this process, we use DCs of
      susceptible BALB/c and resistant C3H/HeJ mice to examine parasite-DC interactions
      in vitro as well as the effector phenotype of T cells primed by parasite-exposed
      DCs in vivo. Our results demonstrate that amastigotes and metacyclics efficiently
      enter and activate DCs of both genetic backgrounds. Infection with amastigotes
      fails to induce CD40-dependent IL-12 production, but rather potentiates IL-4
      production in BALB/c DCs. Upon transfer into syngeneic recipients, amastigote
      exposed BALB/c DCs prime parasite-specific Th cells to produce significantly
      higher levels of IL-4 and IL-10 than their C3H/HeJ counterparts. Transfer studies
      with IL-4(-/-) DCs indicate that this enhanced Th2 priming seen in BALB/c mice is
      partially due to the IL-4 production by amastigote-carrying DCs. These results
      suggest that L. amazonensis amastigotes may condition DCs of a susceptible host
      to a state that favors activation of pathogenic CD4(+) T cells, and thereby
      provide a new perspective on the pathogenesis of cutaneous leishmaniasis and
      protozoan parasite-host interactions in general.

PMID- 11591782
TI  - Quantifying the relationship between multiple immunological parameters and host
      resistance: probing the limits of reductionism.
AB  - Although reductionist experimental designs are excellent for identifying cells,
      molecules, or functions involved in resistance to particular microbes or cancer
      cells, they do not provide an integrated, quantitative view of immune function.
      In the present study, mice were treated with either dexamethasone (DEX) or
      cyclosporin A (CyA), and immune function and host resistance were evaluated.
      Multivariate statistical methods were used to describe the relative importance of
      a broad range of immunological parameters for host resistance in mice treated
      with various dosages of DEX. Multiple regression and logistic regression analysis
      indicated that changes in 24 immunological parameters explained a substantial
      portion of the changes in resistance to B16F10 tumor cells or streptococcus group
      B. However, at least 40% of the change in host resistance remained unexplained.
      DEX at all dosages substantially suppressed numerous relevant immunological
      parameters, but significantly decreased resistance to Listeria monocytogenes only
      at the highest dosage. In contrast, CyA substantially decreased resistance to L.
      monocytogenes at dosages that caused relatively minor suppression of just a few
      immunological parameters (unfortunately, CyA data and host resistance data for L.
      monocytogenes were not suitable for multivariate analysis). These results
      illustrate that mathematical models can be used to explain changes in host
      resistance on the basis of changes in immune parameters, and that moderate
      changes in relevant immunological parameters may not produce the types of changes
      in host resistance expected on the basis of results from reductionist
      experimental designs.

PMID- 11591783
TI  - Phosphatidylinositol 3-kinase confers resistance to encephalomyocarditis and
      herpes simplex virus-induced cell death through the activation of distinct
      downstream effectors.
AB  - The Janus kinase/STAT pathway has emerged as the paradigm of IFN-induced
      protection from viral infections. However, the possible participation of other
      signaling proteins in this protection is not clearly understood. In this report,
      we demonstrate that activation of phosphatidylinositol 3-kinase (PI3K) by either
      serum factors or IFNs blocks cell death induced by encephalomyocarditis virus
      (EMCV) and HSV. This increased resistance to virus-induced cell death does not
      involve the activation of the STAT pathway and occurs in the presence of normal
      viral replication. Interestingly, the cell uses two different PI3K regulated
      pathways to block EMCV- and HSV-induced cell death. The increased sensitivity of
      p85alpha(-/-) embryonic fibroblasts to EMCV-induced cell death is specifically
      corrected by overexpression of an activated allele of Akt/protein kinase B, but
      not activated mitogen-activated protein kinase extracellular kinase. Conversely,
      the augmented sensitivity of p85alpha(-/-) cells to HSV-induced cell death was
      compensated for by expression of an activated form of mitogen-activated protein
      kinase extracellular kinase, but not by activated Akt/protein kinase B. We
      conclude from these data that PI3K-activated pathways function in parallel with
      the Janus kinase/STAT pathway to protect cells from the lethal effects of
      viruses.

PMID- 11591784
TI  - A dual-function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand
      trimer induces T cell-mediated protective immunity against colon cancer in
      carcinoembryonic antigen-transgenic mice.
AB  - A carcinoembryonic Ag (CEA)-based DNA vaccine encoding both CEA and CD40 ligand
      trimer achieved effective tumor-protective immunity against murine colon
      carcinoma in CEA-transgenic mice by activating both naive T cells and dendritic
      cells. Peripheral T cell tolerance to CEA was broken in a prophylactic model by
      this novel, dual-function DNA vaccine, whose efficacy was further enhanced by
      boosts with a recombinant Ab-IL-2 fusion protein (huKS1/4-IL-2). These
      conclusions are supported by four lines of evidence. First, a lethal challenge of
      MC38-CEA-KS Ag murine colon carcinoma cells was for the first time completely
      rejected in 100% of experimental animals treated by oral gavage of this DNA
      vaccine carried by attenuated Salmonella typhimurium, followed by five boosts
      with huKS1/4-IL-2. Second, specific activation of dendritic cells was indicated
      by their marked up-regulation in expression of costimulatory molecules B7.1
      (CD80), B7.2 (CD86), and ICAM-1. Third, a decisive increase over control values
      was observed in both MHC class I Ag-restricted cytotoxicity of CTLs from
      successfully vaccinated mice and secretion of proinflammatory cytokines IFN-gamma
      and IL-12. Fourth, activation of CTLs was augmented, as indicated by up
      regulation of activity markers LFA-1, CD25, CD28, and CD69. Taken together, these
      results suggest that a dual-function DNA vaccine encoding CEA and CD40 ligand
      trimer combined with tumor-targeted IL-2 may be a promising strategy for the
      rational development of DNA-based cancer vaccines for future clinical
      applications.

PMID- 11591785
TI  - Distinct CD8 T cell functions mediate susceptibility to histoplasmosis during
      chronic viral infection.
AB  - It has long been recognized that some viral infections result in generalized
      immune suppression. In acute infections, this period of suppressed immunity is
      relatively short. However, chronic infections associated with a prolonged period
      of immune suppression present far greater risks. Here, we examined the role of
      CD8 T cell responses following viral infection in immunity to systemic
      histoplasmosis. Although wild-type mice with systemic histoplasmosis were able to
      control the infection, those simultaneously infected with lymphocytic
      choriomeningitis virus clone 13 showed reduced immunity with greater fungal
      burden and high mortality. The immune suppression was associated with loss of CD4
      T cells and B cells, generalized splenic atrophy, and inability to mount a
      granulomatous response. Removing the anti-viral CD8 T cells in the coinfected
      mice enabled them to reduce the fungal burden and survive the infection. Their
      lymphoid organs were replenished with CD4 T and B cells. In contrast to wild-type
      mice, perforin-deficient mice infected with lymphocytic choriomeningitis virus
      clone 13 and Histoplasma showed an absence of immunopathology, but the animals
      still died. These results show that CD8 T cells can suppress immunity through
      different mechanisms; although immunopathology is perforin-dependent, lethality
      is perforin-independent.

PMID- 11591786
TI  - Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines.
AB  - Virulence in Toxoplasma gondii is strongly influenced by the genotype of the
      parasite. Type I strains uniformly cause rapid death in mice regardless of the
      host genotype or the challenge dose. In contrast, the outcome of infections with
      type II strains is highly dependent on the challenge dose and the genotype of the
      host. To understand the basis of acute virulence in toxoplasmosis, we compared
      low and high doses of the RH strain (type I) and the ME49/PTG strain (type II) of
      T. gondii in outbred mice. Differences in virulence were reflected in only
      modestly different growth rates in vivo, and both strains disseminated widely to
      different tissues. The key difference in the virulent RH strain was the ability
      to reach high tissue burdens rapidly following a low dose challenge. Lethal
      infections caused by type I (RH) or type II (PTG) strain infections were
      accompanied by extremely elevated levels of Th1 cytokines in the serum, including
      IFN-gamma, TNF-alpha, IL-12, and IL-18. Extensive liver damage and lymphoid
      degeneration accompanied the elevated levels of cytokines produced during lethal
      infection. Increased time of survival following lethal infection with the RH
      strain was provided by neutralization of IL-18, but not TNF-alpha or IFN-gamma.
      Nonlethal infections with a low dose of type II PTG strain parasites were
      characterized by a modest induction of Th1 cytokines that led to control of
      infection and minimal damage to host tissues. Our findings establish that
      overstimulation of immune responses that are normally necessary for protection is
      an important feature of acute toxoplasmosis.

PMID- 11591787
TI  - Lack of CCR2 results in increased mortality and impaired leukocyte activation and
      trafficking following infection of the central nervous system with a neurotropic
      coronavirus.
AB  - In the present study, we evaluated the role of CCR2 in a model of viral-induced
      neurologic disease. An orchestrated expression of chemokines, including the CCR2
      ligands monocyte chemoattractant protein-1/CCL2 and monocyte chemoattractant
      protein-3/CCL7, occurs within the CNS following infection with mouse hepatitis
      virus (MHV). Infection of mice lacking CCR2 (CCR2(-/-)) with MHV resulted in
      increased mortality and enhanced viral recovery from the brain that correlated
      with reduced (p < or = 0.04) T cell and macrophage/microglial (determined by
      F4/80 Ag expression, p < or = 0.004) infiltration into the CNS. Moreover, MHV
      infected CCR2(-/-) mice displayed a significant decrease in Th1-associated
      factors IFN-gamma (p < or = 0.001) and RANTES/CCL5 (p < or = 0.002) within the
      CNS as compared with CCR2(+/+) mice. Further, peripheral CD4(+) and CD8(+) T
      cells from immunized CCR2(-/-) mice displayed a marked reduction in IFN-gamma
      production in response to viral Ag and did not migrate into the CNS of MHV
      infected recombination-activating gene (RAG)1(-/-) mice following adoptive
      transfer. In addition, macrophage/microglial infiltration into the CNS of RAG1(-/
      ) mice receiving CCR2(-/-) splenocytes was reduced (p < or = 0.05), which
      correlated with a reduction in the severity of demyelination (p < or = 0.001) as
      compared with RAG1(-/-) mice receiving splenocytes from CCR2(+/+) mice.
      Collectively, these results indicate an important role for CCR2 in host defense
      and disease by regulating leukocyte activation and trafficking.

PMID- 11591788
TI  - High-dose leptin activates human leukocytes via receptor expression on monocytes.
AB  - Leptin is capable of modulating the immune response. Proinflammatory cytokines
      induce leptin production, and we now demonstrate that leptin can directly
      activate the inflammatory response. RNA expression for the leptin receptor (Ob-R)
      was detectable in human PBMCs. Ob-R expression was examined at the protein level
      by whole blood flow cytometry using an anti-human Ob-R mAb 9F8. The percentage of
      cells expressing leptin receptor was 25 +/- 5% for monocytes, 12 +/- 4% for
      neutrophils, and 5 +/- 1% for lymphocytes (only B lymphocytes). Incubation of
      resting PBMCs with leptin induced rapid expression of TNF-alpha and IL-6 mRNA and
      a dose-dependent production of TNF-alpha and IL-6 by monocytes. Incubation of
      resting PBMCs with high-dose leptin (250 ng/ml, 3-5 days) induced proliferation
      of resting cultured PBMCs and their secretion of TNF-alpha (5-fold), IL-6 (19
      fold), and IFN-gamma (2.5-fold), but had no effect on IL-4 secretion. The effect
      of leptin was distinct from, and additive to, that seen after exposure to
      endotoxin or activation by the mixed lymphocyte reaction. In conclusion, Ob-R is
      expressed on human circulating leukocytes, predominantly on monocytes. At high
      doses, leptin induces proinflammatory cytokine production by resting human PBMCs
      and augments the release of these cytokines from activated PBMCs in a pattern
      compatible with the induction of Th1 cytokines. These results demonstrate that
      leptin has a direct effect on the generation of an inflammatory response. This is
      of relevance when considering leptin therapy and may partly explain the
      relationship among leptin, proinflammatory cytokines, insulin resistance, and
      obesity.

PMID- 11591789
TI  - Induction of hypoxia-inducible factor-1alpha and activation of caspase-3 in
      hypoxia-reoxygenated bone marrow stroma is negatively regulated by the delayed
      production of substance P.
AB  - The bone marrow (BM), which is the major site of immune cell development in the
      adult, responds to different stimuli such as inflammation and hemorrhagic shock.
      Substance P (SP) is the major peptide encoded by the immune/hemopoietic modulator
      gene, preprotachykinin-1 (PPT-I). Differential gene expression using a microarray
      showed that SP reduced hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA levels
      in BM stroma. Because long-term hypoxia induced the expression of PPT-I in BM
      mononuclear cells, we used timeline studies to determine whether PPT-I is central
      to the biologic responses of BM stroma subjected to 30-min hypoxia (pO(2) = 35 mm
      Hg) followed by reoxygenation. HIF-1alpha mRNA and protein levels were increased
      up to 12 h. At this time, beta-PPT-I mRNA was detected with the release of SP at
      16 h. SP release correlated with down-regulation of HIF-1alpha to baseline. A
      direct role for SP in HIF-1alpha expression was demonstrated as follows: 1)
      transient knockout of beta-PPT-I showed an increase in HIF-1alpha expression up
      to 48 h of reoxygenation; and 2) HIF-1alpha expression remained baseline during
      reoxygenation when stroma was subjected to hypoxia in the presence of SP.
      Reoxygenation activated the PPT-I promoter with concomitant nuclear translocation
      of HIF-1alpha that can bind to the respective consensus sequences within the PPT
      I promoter. SP reversed active caspase-3, an indicator of apoptosis and
      erythropoiesis, to homeostasis level after reoxygenation of hypoxic stroma. The
      results show that during reoxgenation the PPT-I gene acts as a negative regulator
      on the expression of HIF-1alpha and active caspase-3 in BM stroma subjected to
      reoxygenation.

PMID- 11591790
TI  - The functional role of rho and rho-associated coiled-coil forming protein kinase
      in eotaxin signaling of eosinophils.
AB  - The CC chemokine eotaxin plays a pivotal role in local accumulation of
      eosinophils. Very little is known about the eotaxin signaling in eosinophils
      except the activation of the mitogen-activated protein (MAP) kinase family. The
      p21 G protein Rho and its substrate Rho-associated coiled-coil forming protein
      kinase (ROCK) regulate the formation of stress fibers and focal adhesions. In the
      present study, we studied the functional relevance of Rho and ROCK in eosinophils
      using the ROCK inhibitor (Y-27632) and exoenzyme C3, a specific Rho inhibitor.
      Eotaxin stimulates activation of Rho A and ROCK II in eosinophils. Exoenzyme C3
      almost completely inhibited the ROCK activity, indicating that ROCK is downstream
      of Rho. We then examined the role of Rho and ROCK in eosinophil chemotaxis. The
      eotaxin-induced eosinophil chemotaxis was significantly inhibited by exoenzyme C3
      or Y-27632. Because extracellular signal-regulated kinase (ERK)1/2 and p38 MAP
      kinases are activated by eotaxin and are critical for eosinophil chemotaxis, we
      investigated whether Rho and ROCK are upstream of these MAP kinases. C3 partially
      inhibited eotaxin-induced phosphorylation of ERK1/2 but not p38. In contrast,
      neither ERK1/2 nor p38 phosphorylation was abrogated by Y-27632. Both C3 and Y
      27632 reduced reactive oxygen species production from eosinophils. We conclude
      that both Rho and ROCK are important for eosinophil chemotaxis and reactive
      oxygen species production. There is a dichotomy of downstream signaling pathways
      of Rho, namely, Rho-ROCK and Rho-ERK pathways. Taken together, eosinophil
      chemotaxis is regulated by multiple signaling pathways that involve at least
      ROCK, ERK, and p38 MAP kinase.

PMID- 11591791
TI  - Intracisternally localized bacterial DNA containing CpG motifs induces
      meningitis.
AB  - Unmethylated CpG motifs are frequently found in bacterial DNA, and have recently
      been shown to exert immunostimulatory effects on leukocytes. Since bacterial
      infections in the CNS will lead to local release of prokaryotic DNA, we wanted to
      investigate whether such an event might trigger meningitis. To that end, we have
      intracisternally injected mice and rats with bacterial DNA and oligonucleotides
      containing CpG motifs. Histopathological signs of meningitis were evident within
      12 h and lasted for at least 14 days, and were characterized by an influx of
      monocytic, Mac-3(+) cells and by a lack of T lymphocytes. To study the mechanisms
      whereby unmethylated CpG DNA gives rise to meningitis, we deleted the
      monocyte/macrophage population leading to abrogation of brain inflammation. Also,
      interaction with NF-kappaB using antisense technology led to down-regulation of
      proinflammatory cytokine production and frequency of meningitis. Furthermore,
      specific interactions with vascular selectin expression and inhibition of NO
      synthase led to a significant amelioration of meningitis, altogether indicating
      that this condition is dependent on macrophages and their products. In contrast,
      neutrophils, NK cells, T/B lymphocytes, IL-12, and complement system were not
      instrumental in meningitis triggered by bacterial DNA containing CpG motifs. This
      study proves that bacterial DNA containing unmethylated CpG motifs induces
      meningitis, and indicates that this condition is mediated in vivo by activated
      macrophages.

PMID- 11591792
TI  - Cockroach allergen-induced eosinophilic airway inflammation in HLA-DQ/human
      CD4(+) transgenic mice.
AB  - Airway eosinophilic inflammation is a characteristic feature of allergic asthma.
      Exposure to allergens produced by the German cockroach (Blattella germanica) is a
      risk factor for allergic disease in genetically predisposed individuals, and has
      been linked to an increase in asthma morbidity among cockroach-sensitive inner
      city children. To determine the role and contribution of specific HLA class II in
      the pathogenesis of allergic airway inflammation in cockroach-induced asthma, we
      generated double-transgenic, double-knockout mice expressing human HLA-DQ8, HLA
      DQ6, and CD4 molecules in the absence of mouse class II and mouse CD4. Mice were
      actively immunized and later challenged intranasally with cockroach allergen
      extract. These mice developed bronchoalveolar lavage fluid (BALF) eosinophilia
      and pulmonary eosinophilia. This was accompanied by an increase in total protein
      levels, IL-5, and IL-13 in BALF. There were also elevated levels of cockroach
      specific serum IgG1 and total serum IgE. Histological analysis revealed
      peribronchial and perivascular eosinophilic inflammation in cockroach-treated
      mice. Other pathologic changes in the airways were epithelial cell hypertrophy
      and mucus production. Treatment with anti-DQ mAb significantly reduced pulmonary
      and BALF eosinophilia in cockroach allergen-sensitized mice. Abeta(0) mice and
      transgenic mice expressing human CD4 molecule alone (without class II) or human
      HLA-DQ8 molecule (without CD4) treated in the same fashion showed no eosinophilia
      in bronchoalveolar fluid and no pulmonary parenchymal inflammation. Our results
      provide direct evidence that HLA-DQ molecules and CD4 T cells mediate cockroach
      induced eosinophilic inflammation in the airways.

PMID- 11591793
TI  - Constitutive expression of macrophage-inflammatory protein 2 (MIP-2) mRNA in bone
      marrow gives rise to peripheral neutrophils with preformed MIP-2 protein.
AB  - Macrophage-inflammatory protein 2 (MIP-2) is a major CXC chemokine involved in
      the migration of polymorphonuclear neutrophils (PMNs) to sites of inflammation.
      Although cell culture experiments have identified different cell types that can
      produce MIP-2, the cellular sources in vivo are not clearly defined. By using
      immunohistochemical staining and analysis of chemokine mRNA expression, the
      present study aimed to localize cells producing MIP-2 in tissues of normal mice
      and mice challenged with Yersinia enterocolitica. The results showed a
      constitutive expression of MIP-2 mRNA in bone marrow (BM) of normal mice, but not
      in other organs such as spleen, lung, or liver. MIP-2 protein was found in all
      organs tested but it was exclusively associated with PMNs that stained positive
      with the cell surface marker Gr-1. Bacterial infection caused a 5-fold increase
      in the number of MIP-2-positive PMNs recruited to spleens concomitant with a
      strong increase of splenic MIP-2 mRNA. This correlated well with a 3-fold loss of
      MIP-2-producing cells in BM. Because MIP-2 mRNA expression in PMNs was increased
      after stimulation with TNF, the results indicate that newly recruited PMNs can
      supplement their MIP-2 content through TNF-stimulated transcription. Together,
      the data imply a constitutive production of MIP-2 by a subset of PMNs in BM and
      argue for the possibility of a rapid mobilization of MIP-2 through its storage in
      circulating PMNs.

PMID- 11591794
TI  - Meningeal and perivascular macrophages of the central nervous system play a
      protective role during bacterial meningitis.
AB  - Meningeal (MM) and perivascular macrophages (PVM) constitute major populations of
      resident macrophages in the CNS that can be distinguished from microglial cells.
      So far, there is no direct evidence that demonstrates a possible role of MM and
      PVM in the CNS during normal or pathologic conditions. To elucidate the role of
      the MM and PVM during CNS inflammation, we have developed a strategy using a
      single intraventricular injection of mannosylated clodronate liposomes, which
      results in a complete and selective depletion of the PVM and MM from the CNS.
      Depletion of the MM and PVM during experimental pneumococcal meningitis resulted
      in increased illness, which correlated with higher bacteria counts in the
      cerebrospinal fluid and blood. This was associated with a decreased influx of
      leukocytes into the cerebrospinal fluid, which occurred despite an elevated
      production of relevant chemokines (e.g., macrophage-inflammatory protein-2) and a
      higher expression of vascular adhesion molecules (e.g., VCAM-1). In contrast, the
      higher bacterial counts correlated with elevated production of local and systemic
      inflammatory mediators (e.g., IL-6) indicating enhanced local leukocyte and
      systemic immune activation, and this may explain the worsening of the clinical
      signs. These findings show that the PVM and MM play a protective role during
      bacterial meningitis and suggest that a primary action of these macrophages is to
      facilitate the influx of leukocytes at the blood-brain barrier. More in general,
      we demonstrate for the first time that the PVM and MM play a crucial role during
      inflammation in the CNS.

PMID- 11591795
TI  - Contribution of anaphylatoxin C5a to late airway responses after repeated
      exposure of antigen to allergic rats.
AB  - We attempted to elucidate the contribution of complement to allergic asthma. Rat
      sensitized to OVA received repeated intratracheal exposures to OVA for up to 3
      consecutive days, and pulmonary resistance was then estimated for up to 6 h after
      the last exposure. Whereas the immediate airway response (IAR) in terms of R(L)
      tended to decrease in proportion to the number of OVA exposures, late airway
      response (LAR) became prominent only after three. Although premedication with two
      kinds of complement inhibitors, soluble complement receptor type 1 (sCR1) or
      nafamostat mesylate, resulted in inhibition of the IAR after either a single or a
      double exposure, the LAR was inhibited after the triple. Premedication with a C5a
      receptor antagonist (C5aRA) before every exposure to OVA also inhibited the LAR
      after three. Repeated OVA exposure resulted in eosinophil and neutrophil
      infiltration into the bronchial submucosa which was suppressed by premedication
      with sCR1 or C5aRA. Up-regulation of C5aR mRNA was shown in lungs after triple
      OVA exposure, but almost no up-regulation of C3aR. Pretreatment with sCR1 or
      C5aRA suppressed the up-regulation of C5aR expression as well as cytokine
      messages in the lungs. The suppression of LAR by pretreatment with sCR1 was
      reversed by intratracheal instillation of rat C5a desArg the action of which was
      inhibited by C5aRA. In contrast, rat C3a desArg or cytokine-induced neutrophil
      chemoattractant-1 induced cellular infiltration into the bronchial submucosa by
      costimulation with OVA, but these had no influence on the LAR. These differences
      might be explained by the fact that costimulation with OVA and C5a
      synergistically potentiated IAR, whereas that with OVA and either C3a or cytokine
      induced neutrophil chemoattractant-1 did not. C5a generated by Ag-Ab complexes
      helps in the production of cytokines and contributes to the LAR after repeated
      exposure to Ag.

PMID- 11591796
TI  - Production of colony-stimulating factors and IL-5 by organs from three types of
      mice with inflammatory disease due to loss of the suppressor of cytokine
      signaling-1.
AB  - Organs from neonatal mice dying from IFN-gamma-dependent inflammatory disease
      initiated by loss of the gene encoding the suppressor of cytokine signaling-1
      (SOCS-1) had a normal capacity to produce G-CSF in vitro but a reduced capacity
      to produce GM-CSF, most evident with the lung, and some reduction in the
      production of M-CSF by muscle tissue. In contrast, organs from mice lacking the
      genes for both SOCS-1 and IFN-gamma had a normal capacity to produce CSFs. Organs
      from young adult mice dying with polymyositis and myocarditis that lacked SOCS-1
      but were heterozygous for IFN-gamma had a normal capacity to produce GM-CSF and M
      CSF, but muscle tissue produced significantly increased amounts of G-CSF and IL-5
      with IL-5 production also being elevated for the salivary gland, thymus, and
      heart. Loss of the IFN-gamma gene alone had no impact on organ production of
      these cytokines in vitro. In none of the inflammatory disease models was IL-3
      production detected. The SOCS-1 protein appears to have no direct influence on
      the cellular production of these cytokines and the abnormalities observed either
      depend on the coaction of IFN-gamma, or more likely, are linked with the invasion
      and destruction of tissue by T lymphocytes, macrophages, eosinophils, and
      neutrophils. The ability of local organs to produce these proinflammatory
      cytokines could contribute to the development and progression of these
      inflammatory lesions.

PMID- 11591797
TI  - Critical role for IL-13 in the development of allergen-induced airway
      hyperreactivity.
AB  - Airway hyperresponsiveness to a variety of specific and nonspecific stimuli is a
      cardinal feature of asthma, which affects nearly 10% of the population in
      industrialized countries. Eosinophilic pulmonary inflammation, eosinophil-derived
      products, as well as Th2 cytokines IL-13, IL-4, and IL-5, have been associated
      with the development of airway hyperreactivity (AHR), but the specific
      immunological basis underlying the development of AHR remains controversial.
      Herein we show that mice with targeted deletion of IL-13 failed to develop
      allergen-induced AHR, despite the presence of vigorous Th2-biased, eosinophilic
      pulmonary inflammation. However, AHR was restored in IL-13(-/-) mice by the
      administration of recombinant IL-13. Moreover, adoptive transfer of OVA-specific
      Th2 cells generated from TCR-transgenic IL-13(-/-) mice failed to induce AHR in
      recipient SCID mice, although such IL-13(-/-) Th2 cells produced high levels of
      IL-4 and IL-5 and induced significant airway inflammation. These studies
      definitively demonstrate that IL-13 is necessary and sufficient for the induction
      of AHR and that eosinophilic airway inflammation in the absence of IL-13 is
      inadequate for the induction of AHR. Therefore, treatment of human asthma with
      antagonists of IL-13 may be very effective.

PMID- 11591798
TI  - Adenosine-dependent airway inflammation and hyperresponsiveness in partially
      adenosine deaminase-deficient mice.
AB  - Adenosine is a signaling nucleoside that is elevated in the lungs of asthmatics.
      We have engineered a mouse model that has elevated levels of adenosine as a
      result of the partial expression of the enzyme that metabolizes adenosine,
      adenosine deaminase (ADA). Mice with lowered levels of ADA enzymatic activity
      were generated by the ectopic expression of an ADA minigene in the
      gastrointestinal tract of otherwise ADA-deficient mice. These mice developed
      progressive lung inflammation and damage and died at 4-5 mo of age from
      respiratory distress. Associated with this phenotype was a progressive increase
      in lung adenosine levels. Examination of airway physiology at 6 wk of age
      revealed alterations in airway hyperresponsiveness. This was reversed following
      the lowering of adenosine levels using ADA enzyme therapy and also through the
      use of the adenosine receptor antagonist theophylline, implicating both the
      nucleoside and its receptors in airway physiological alterations. All four
      adenosine receptors were expressed in the lungs of both control and partially ADA
      deficient mice. However, transcript levels for the A(1), A(2B), and A(3)
      adenosine receptors were significantly elevated in partially ADA-deficient lungs.
      There was a significant increase in alveolar macrophages, and monocyte
      chemoattractant protein-3 was found to be elevated in the bronchial epithelium of
      these mice, which may have important implications in the regulation of pulmonary
      inflammation and airway hyperresponsiveness. Collectively, these findings suggest
      that elevations in adenosine can directly impact lung inflammation and
      physiology.

PMID- 11591799
TI  - AMD3100, a potent and specific antagonist of the stromal cell-derived factor-1
      chemokine receptor CXCR4, inhibits autoimmune joint inflammation in IFN-gamma
      receptor-deficient mice.
AB  - Autoimmune collagen-induced arthritis (CIA) in IFN-gammaR-deficient DBA/1 mice
      was shown to be reduced in severity by treatment with the bicyclam derivative
      AMD3100, a specific antagonist of the interaction between the chemokine stromal
      cell-derived factor-1 (SDF-1) and its receptor CXCR4. The beneficial effect of
      the CXCR4 antagonist was demonstrable when treatment was initiated between the
      time of immunization and appearance of the first symptoms. Treatment also reduced
      the delayed-type hypersensitivity response to the autoantigen, collagen type II.
      These observations are indicative of an action on a late event in the
      pathogenesis, such as chemokine-mediated attraction of leukocytes toward joint
      tissues. The notion of SDF-1 involvement was further supported by the observation
      that exogenous SDF-1 injected in periarthritic tissue elicited an inflammatory
      response that could be inhibited by AMD3100. The majority of leukocytes harvested
      from inflamed joints of mice with CIA were found to be Mac-1(+) and CXCR4(+), and
      AMD3100 was demonstrated to interfere specifically with chemotaxis and Ca(2+)
      mobilization induced in vitro by SDF-1 on Mac-1(+)/CXCR4(+) splenocytes. We
      conclude that SDF-1 plays a central role in the pathogenesis of murine CIA, by
      attracting Mac-1(+)/CXCR4(+) cells to the inflamed joints.

PMID- 11591800
TI  - Mature dendritic cells infiltrate the T cell-rich region of oral mucosa in
      chronic periodontitis: in situ, in vivo, and in vitro studies.
AB  - Previous studies have analyzed the lymphoid and myeloid foci within the gingival
      mucosa in health and chronic periodontitis (CP); however, the principal APCs
      responsible for the formation and organizational structure of these foci in CP
      have not been defined. We show that in human CP tissues, CD1a(+) immature
      Langerhans cells predominantly infiltrate the gingival epithelium, whereas
      CD83(+) mature dendritic cells (DCs) specifically infiltrate the CD4(+) lymphoid
      rich lamina propria. In vivo evidence shows that exacerbation of CP results in
      increased levels of proinflammatory cytokines that mediate DC
      activation/maturation, but also of counterregulatory cytokines that may prevent a
      Th-polarized response. Consistently, in vitro-generated monocyte-derived DCs
      pulsed with Porphyromonas gingivalis strain 381 or its LPS undergo maturation, up
      regulate accessory molecules, and release proinflammatory (IL-1beta, PGE(2)) and
      Th (IL-10, IL-12) cytokines. Interestingly, the IL-10:IL-12 ratio elicited from
      P. gingivalis-pulsed DCs was 3-fold higher than that from Escherichia coli-pulsed
      DCs. This may account for the significantly (p < 0.05) lower proliferation of
      autologous CD4(+) T cells and reduced release of IFN-gamma elicited by P.
      gingivalis-pulsed DCs. Taken together, these findings suggest a previously
      unreported mechanism for the pathophysiology of CP, involving the activation and
      in situ maturation of DCs by the oral pathogen P. gingivalis, leading to release
      of counterregulatory cytokines and the formation of T cell-DC foci.

PMID- 11591801
TI  - Overexpression of the Wiskott-Aldrich syndrome protein N-terminal domain in
      transgenic mice inhibits T cell proliferative responses via TCR signaling without
      affecting cytoskeletal rearrangements.
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by
      thrombocytopenia with small platelets, severe eczema, and recurrent infections
      due to defects in the immune system. The disease arises from mutations in the
      gene encoding the WAS protein (WASP), which plays a role as an adaptor molecule
      in signal transduction accompanied by cytoskeletal rearrangement in T cells. To
      investigate the functional domain of WASP, we developed transgenic mice
      overexpressing the WASP N-terminal region (exon 1-5) including the Ena/VASP
      homology 1 (pleckstrin homology/WASP homology 1) domain, in which the majority of
      mutations in WAS patients have been observed. WASP transgenic mice develop and
      grow normally under the specific pathogen-free environment, and showed normal
      lymphocyte development. However, proliferative responses and cytokine production
      induced by TCR stimulation were strongly inhibited in transgenic mice, whereas Ag
      receptor capping and actin polymerization were normal. These findings suggest
      that overexpressed Ena/VASP homology 1 (pleckstrin homology/WASP homology 1)
      domain of WASP inhibits the signaling from TCR without coupling of cytoskeletal
      rearrangement. WASP transgenic mice shown here could be valuable tools for
      further understanding the WASP-mediated processes.

PMID- 11591802
TI  - T cell activation in rheumatoid synovium is B cell dependent.
AB  - Rheumatoid arthritis results from a T cell-driven inflammation in the synovial
      membrane that is frequently associated with the formation of tertiary lymphoid
      structures. The significance of this extranodal lymphoid neogenesis is unknown.
      Microdissection was used to isolate CD4 T cells residing in synovial tissue T
      cell/B cell follicles. CD4 T cells with identical TCR sequences were represented
      in independent, nonadjacent follicles, suggesting recognition of the same Ag in
      different germinal centers. When adoptively transferred into rheumatoid arthritis
      synovium-SCID mouse chimeras, these CD4 T cell clones enhanced the production of
      IFN-gamma, IL-1beta, and TNF-alpha. In vivo activity of adoptively transferred
      CD4 T cells required matching of HLA-DRB1 alleles and also the presence of T
      cell/B cell follicles. HLA-DRB1-matched synovial tissues that were infiltrated by
      T cells, macrophages, and dendritic cells, but that lacked B cells, did not
      support the activation of adoptively transferred CD4 T cell clones, raising the
      possibility that B cells provided a critical function in T cell activation or
      harbored the relevant Ag. Dependence of T cell activation on B cells was
      confirmed in B cell depletion studies. Treatment of chimeric mice with anti-CD20
      mAb inhibited the production of IFN-gamma and IL-1beta, indicating that APCs
      other than B cells could not substitute in maintaining T cell activation. The
      central role of B cells in synovial inflammation identifies them as excellent
      targets for immunosuppressive therapy.

PMID- 11591803
TI  - Apoptosis-inducing human-origin Fcepsilon-Bak chimeric proteins for targeted
      elimination of mast cells and basophils: a new approach for allergy treatment.
AB  - During the past few years, many chimeric proteins have been developed to
      specifically target and kill cells expressing specific surface molecules.
      Generally these molecules carry a bacterial or plant toxin to destroy the
      unwanted cells. The major obstacle regarding these molecules in their clinical
      application is the immunogenicity and nonspecific toxicity associated with
      bacterial or plant toxins. We lately reported a new approach for construction of
      chimeric proteins: we successfully replaced bacterial or plant toxins with human
      apoptosis-inducing proteins. The resulting chimeras were shown to specifically
      induce apoptosis in the target cells. Taking advantage of the human apoptosis
      inducing proteins Bak and Bax as novel killing components, we have now
      constructed new chimeric proteins targeted against the human FcepsilonRI,
      expressed mainly on mast cells and basophils. These cells are the main effectors
      of the allergic response. Treatment of the target cells with the new chimeric
      proteins, termed Fcepsilon-Bak/Bax, had a dramatic effect on cell survival,
      causing apoptosis. The effect was specific to cells expressing the FcepsilonRI of
      both human and, very unexpectedly, also of mouse origin. Moreover, interaction of
      the chimeric proteins with the mast cells did not cause degranulation. Fcepsilon
      Bak/Bax are new chimeric proteins of human origin and, as such, are expected to
      be both less immunogenic and less toxic and, thus, may be specific and efficient
      reagents for the treatment of allergic diseases.

PMID- 11591804
TI  - Unique T cell effector functions elicited by Plasmodium falciparum epitopes in
      malaria-exposed Africans tested by three T cell assays.
AB  - Natural immunity to malaria is characterized by low level CD4 T cell reactivity
      detected by either lymphoproliferation or IFN-gamma secretion. Here we show a
      doubling in the detection rate of responders to the carboxyl terminus of
      circumsporozoite protein (CS) of Plasmodium falciparum by employing three T cell
      assays simultaneously: rapid IFN-gamma secretion (ex vivo ELISPOT), IFN-gamma
      secretion after reactivation of memory T cells and expansion in vitro (cultured
      ELISPOT), and lymphoproliferation. Remarkably, for no individual peptide did a
      positive response for one T cell effector function correlate with any other. Thus
      these CS epitopes elicited unique T cell response patterns in malaria-exposed
      donors. Novel or important epitope responses may therefore be missed if only one
      T cell assay is employed. A borderline correlation was found between anti-CS Ab
      levels and proliferative responses, but no correlation was found with ex vivo or
      cultured IFN-gamma responses. This suggested that the proliferating population,
      but not the IFN-gamma-secreting cells, contained cells that provide help for Ab
      production. The data suggest that natural immunity to malaria is a complex
      function of T cell subgroups with different effector functions and has important
      implications for future studies of natural T cell immunity.

PMID- 11591805
TI  - Identification of HLA-B27-restricted peptides from the Chlamydia trachomatis
      proteome with possible relevance to HLA-B27-associated diseases.
AB  - The association of HLA-B27 with ankylosing spondylitis and reactive arthritis is
      the strongest one known between an MHC class I Ag and a disease. We have searched
      the proteome of the bacterium Chlamydia trachomatis for HLA-B27 binding peptides
      that are stimulatory for CD8(+) cells both in a model of HLA-B27 transgenic mice
      and in patients. This was done by combining two biomathematical computer
      programs, the first of which predicts HLA-B27 peptide binding epitopes, and the
      second the probability of HLA-B27 peptide generation by the proteasome system.
      After preselection, immunodominant peptides were identified by Ag-specific flow
      cytometry. Using this approach we have identified for the first time nine
      peptides derived from different C. trachomatis proteins that are stimulatory for
      CD8(+) T cells. Eight of these nine murine-derived peptides were recognized by
      cytotoxic T cells. The same strategy was used to identify B27-restricted
      chlamydial peptides in three patients with reactive arthritis. Eleven peptides
      were found to be stimulatory for patient-derived CD8(+) T cells, of which eight
      overlapped those found in mice. Additionally, we applied the tetramer technology,
      showing that a B27/chlamydial peptide containing one of the chlamydial peptides
      stained CD8(+) T cells in patients with Chlamydia-induced arthritis. This
      comprehensive approach offers the possibility of clarifying the pathogenesis of
      B27-associated diseases.

PMID- 11591806
TI  - A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived
      factor-1, in the development of bone marrow metastases in neuroblastoma.
AB  - The homing of hemopoietic stem cells to the bone marrow is mediated by specific
      interactions occurring between CXCR4, which is expressed on hemopoietic stem
      cells, and its ligand, stromal cell-derived factor-1 (SDF-1), a CXC chemokine
      secreted by bone marrow stromal cells. In the present study we evaluated the
      possibility that neuroblastoma cells use a mechanism similar to that used by
      hemopoietic stem cells to home to the bone marrow and adhere to bone marrow
      stromal cells. Our study suggests that CXCR4 expression may be a general
      characteristic of neuroblastoma cells. SH-SY5Y neuroblastoma cells express not
      only CXCR4, but also its ligand, SDF-1. CXCR4 expression on SH-SY5Y neuroblastoma
      cells is tightly regulated by tumor cell-derived SDF-1, as demonstrated by the
      ability of neutralizing Abs against human SDF-1alpha to up-regulate CXCR4
      expression on the tumor cells. The reduction in CXCR4 expression following short
      term exposure to recombinant human SDF-1alpha can be recovered as a result of de
      novo receptor synthesis. Recombinant human SDF-1alpha induces the migration of
      CXCR4-expressing SH-SY5Y neuroblastoma cells in CXCR4- and heterotrimeric G
      protein-dependent manners. Furthermore, SH-SY5Y cells interact at multiple levels
      with bone marrow components, as evidenced by the fact that bone marrow-derived
      constituents promote SH-SY5Y cell migration, adhesion to bone marrow stromal
      cells, and proliferation. These results suggest that SH-SY5Y neuroblastoma cells
      are equipped with adequate machinery to support their homing to the bone marrow.
      Therefore, the ability of neuroblastoma tumors to preferentially form metastases
      in the bone marrow may be influenced by a set of complex CXCR4-SDF-1
      interactions.

PMID- 11591807
TI  - Retrovirally transduced human dendritic cells can generate T cells recognizing
      multiple MHC class I and class II epitopes from the melanoma antigen glycoprotein
      100.
AB  - Involvement of tumor-Ag specific CD4(+) and CD8(+) T cells could be critical in
      the generation of an effective immunotherapy for cancer. In an attempt to
      optimize the T cell response against defined tumor Ags, we previously developed a
      method allowing transgene expression in human dendritic cells (DCs) using
      retroviral vectors. One advantage of using gene-modified DCs is the potential
      ability to generate CD8(+) T cells against multiple class I-restricted epitopes
      within the Ag, thereby eliciting a broad antitumor immune response. To test this,
      we generated tumor-reactive CD8(+) T cells with DCs transduced with the melanoma
      Ag gp100, for which a number of HLA-A2-restricted epitopes have been described.
      Using gp100-transduced DCs, we were indeed able to raise T cells recognizing
      three distinct HLA-A2 epitopes within the Ag, gp100(154-162), gp100(209-217), and
      gp100(280-288). We next tested the ability of transduced DCs to raise class II
      restricted CD4(+) T cells. Interestingly, stimulation with gp100-transduced DCs
      resulted in the generation of CD4(+) T cells specific for a novel HLA
      DRbeta1*0701-restricted epitope of gp100. The minimal determinant of this epitope
      was defined as gp100(174-190) (TGRAMLGTHTMEVTVYH). These observations suggest
      that retrovirally transduced DCs have the capacity to present multiple MHC class
      I- and class II-restricted peptides derived from a tumor Ag, thereby eliciting a
      robust immune response against that Ag.

PMID- 11591808
TI  - Secondhand smoke induces allergic sensitization in mice.
AB  - Epidemiological studies have suggested increased prevalence of atopy in children
      of maternal smokers. Although secondhand smoke or environmental tobacco smoke
      (ETS) has been shown to augment allergic responses, its role in atopic
      sensitization is still controversial. We studied whether ETS could initiate a Th2
      response and thus induce primary allergic sensitization. Mice were exposed for 10
      consecutive days to either 1% aerosolized OVA, ETS (5 cigarettes), or both ETS
      and OVA. C57BL/6 mice receiving both ETS and OVA developed OVA-specific IgE and
      IgG1, 12, 14, and 25 days after the initial exposure, whereas those receiving OVA
      alone did not. Thirty days after the initial challenge (20 days after its
      completion), mice were re-exposed to OVA. Bronchoalveolar lavage performed 24 h
      later revealed an influx of eosinophils in the group initially challenged with
      both ETS and OVA, but not in those exposed to ETS alone or OVA alone. Increases
      in IL-5, GM-CSF, and IL-2 were observed in bronchoalveolar lavage from this
      OVA/ETS-exposed group, whereas IFN-gamma levels were significantly inhibited.
      These results suggest that ETS can induce allergic sensitization to a normally
      harmless Ag, and they may explain why secondhand smoke is a major risk factor for
      the development of allergy in children.

PMID- 11591809
TI  - How do you cross an armadillo with a porcupine and other problems that arise from
      naming proteins. By Caveman.

PMID- 11591810
TI  - Endogenous inhibitors of angiogenesis.

PMID- 11591811
TI  - Mechanism and role of PDZ domains in signaling complex assembly.
AB  - PDZ domains are protein-protein recognition modules that play a central role in
      organizing diverse cell signaling assemblies. These domains specifically
      recognize short C-terminal peptide motifs, but can also recognize internal
      sequences that structurally mimic a terminus. PDZ domains can therefore be used
      in combination to bind an array of target proteins or to oligomerize into
      branched networks. Several PDZ-domain-containing proteins play an important role
      in the transport, localization and assembly of supramolecular signaling
      complexes. Examples of such PDZ-mediated assemblies exist in Drosophila
      photoreceptor cells and at mammalian synapses. The predominance of PDZ domains in
      metazoans indicates that this highly specialized scaffolding module probably
      evolved in response to the increased signaling needs of multicellular organisms.

PMID- 11591812
TI  - Targeting of Ran: variation on a common theme?
AB  - The Ran GTPase plays a key role in nucleocytoplasmic transport. In its GTP-bound
      form, it directly interacts with members of the importin beta family of nuclear
      transport receptors and modulates their association with cargo. Work in cell-free
      higher-eukaryote systems has demonstrated additional roles for Ran in spindle and
      nuclear envelope formation during mitosis. However, until recently, no Ran-target
      proteins in these cellular processes were known. Several groups have now
      identified importin beta as one important target of Ran during mitotic spindle
      formation. This finding suggests that Ran uses the same effectors to regulate
      different cellular processes.

PMID- 11591813
TI  - CDK1-mediated phosphorylation of the RIIalpha regulatory subunit of PKA works as
      a molecular switch that promotes dissociation of RIIalpha from centrosomes at
      mitosis.
AB  - Protein kinase A regulatory subunit RIIalpha is tightly bound to centrosomal
      structures during interphase through interaction with the A-kinase anchoring
      protein AKAP450, but dissociates and redistributes from centrosomes at mitosis.
      The cyclin B-p34(cdc2) kinase (CDK1) has been shown to phosphorylate RIIalpha on
      T54 and this has been proposed to alter the subcellular localization of RIIalpha.
      We have made stable transfectants from an RIIalpha-deficient leukemia cell line
      (Reh) that expresses either wild-type or mutant RIIalpha (RIIalpha(T54E)). When
      expressed, RIIalpha detaches from centrosomes at mitosis and dissociates from its
      centrosomal location in purified nucleus-centrosome complexes by incubation with
      CDK1 in vitro. By contrast, centrosomal RIIalpha(T54E) is not redistributed at
      mitosis, remains mostly associated with centrosomes during all phases of the cell
      cycle and cannot be solubilized by CDK1 in vitro. Furthermore, RIIalpha is
      solubilized from particular cell fractions and changes affinity for AKAP450 in
      the presence of CDK1. D and V mutations of T54 also reduce affinity for the N
      terminal RII-binding domain of AKAP450, whereas small neutral residues do not
      change affinity detected by surface plasmon resonance. In addition, only
      RIIalpha(T54E) interacts with AKAP450 in a RIPA-soluble extract from mitotic
      cells. Finally, microtubule repolymerization from mitotic centrosomes of the
      RIIalpha(T54E) transfectant is poorer and occurs at a lower frequency than that
      of RIIalpha transfectants. Our results suggest that T54 phosphorylation of
      RIIalpha by CDK1 might serve to regulate the centrosomal association of PKA
      during the cell cycle.

PMID- 11591814
TI  - Regulation of anchoring of the RIIalpha regulatory subunit of PKA to AKAP95 by
      threonine phosphorylation of RIIalpha: implications for chromosome dynamics at
      mitosis.
AB  - CDK1 phosphorylates the A-kinase regulatory subunit RIIalpha on threonine 54
      (T54) at mitosis, an event proposed to alter the subcellular localization of
      RIIalpha. Using an RIIalpha-deficient leukemic cell line (Reh) and stably
      transfected Reh cell clones expressing wild-type RIIalpha or an RIIalpha(T54E)
      mutant, we show that RIIalpha associates with chromatin-bound A-kinase anchoring
      protein AKAP95 at mitosis and that this interaction involves phosphorylation of
      RIIalpha on T54. During interphase, both RIIalpha and RIIalpha(T54E) exhibit a
      centrosome-Golgi localization, whereas AKAP95 is intranuclear. At mitosis and in
      a mitotic extract, most RIIalpha, but not RIIalpha(T54E), co-fractionates with
      chromatin, onto which it associates with AKAP95. This correlates with T54
      phosphorylation of RIIalpha. Disrupting AKAP95-RIIalpha anchoring or depleting
      RIIalpha from the mitotic extract promotes premature chromatin decondensation. In
      a nuclear reconstitution assay that mimics mitotic nuclear reformation, RIIalpha
      is threonine dephosphorylated and dissociates from AKAP95 prior to assembly of
      nuclear membranes. Lastly, the Reh cell line exhibits premature chromatin
      decondensation in vitro, which can be rescued by addition of wild-type RIIalpha
      or an RIIalpha(T54D) mutant, but not RIIalpha(T54E, A, L or V) mutants. Our
      results suggest that CDK1-mediated T54 phosphorylation of RIIalpha constitutes a
      molecular switch controlling anchoring of RIIalpha to chromatin-bound AKAP95,
      where the PKA-AKAP95 complex participates in remodeling chromatin during mitosis.

PMID- 11591815
TI  - Positive regulation of cell-cell and cell-substrate adhesion by protein kinase A.
AB  - Integrin receptor activation is an important regulatory mechanism for cell
      substrate and cell-cell adhesion. In this study, we explore a signaling pathway
      activated by mAb 12G10, an antibody that can activate beta(1) integrins and
      induce integrin-mediated cell-cell and cell-substrate adhesion. We have found
      that the cAMP-dependent protein kinase (PKA) is required for both mAb 12G10
      induced cell-cell and cell-substrate adhesion of HT-1080 cells. Binding of mAb
      12G10 to beta(1) integrins stimulates an increase in intracellular cAMP levels
      and PKA activity, and a concomitant shift in the localization of the PKA type II
      regulatory subunits from the cytoplasm to areas where integrins expressing the
      12G10 epitope are located. MAb 12G10-induced cell-cell adhesion was mimicked by a
      combination of clustering beta(1) integrins and elevating PKA activity with Sp
      adenosine-3',5'-cyclic monophosphorothioate or forskolin. We also show that two
      processes required for HT-1080 cell-cell adhesion, integrin clustering and F
      actin polymerization are both dependent on PKA. Taken together, our data suggest
      that PKA plays a key role in the signaling pathway, resulting from activation of
      beta(1) integrins, and that this enzyme may be required for upregulation of cell
      substrate and cell-cell adhesion.

PMID- 11591816
TI  - Rho-dependent transfer of Citron-kinase to the cleavage furrow of dividing cells.
AB  - Citron-kinase (Citron-K) is a Rho effector working in cytokinesis. It is enriched
      in cleavage furrow, but how Rho mobilizes Citron-K remains unknown. Using anti
      Citron antibody and a Citron-K Green Fluorescence Protein (GFP)-fusion, we
      monitored its localization in cell cycle. We have found: (1) Citron-K is present
      as aggregates in interphase cells, disperses throughout the cytoplasm in
      prometaphase, translocates to cell cortex in anaphase and accumulates in cleavage
      furrow in telophase; (2) Rho colocalizes with Citron-K in the cortex of ana- to
      telophase cells and the two proteins are concentrated in the cleavage furrow and
      to the midbody; (3) inactivation of Rho by C3 exoenzyme does not affect the
      dispersion of Citron-K in prometaphase, but prevented its transfer to the cell
      cortex, and Citron-K stays in association with the midzone spindles of C3
      exoenzyme-treated cells. To clarify further the mechanism of the Rho-mediated
      transfer and concentration of Citron-K in cleavage furrow, we expressed active
      Val14RhoA in interphase cells expressing GFP-Citron-K. Val14RhoA expression
      transferred Citron-K to the ventral cortex of interphase cells, where it formed
      band-like structures in a complex with Rho. This structure was localized at the
      same plane as actin stress fibers, and they exclude each other. Disruption of F
      actin abolished the band and dispersed the Citron-K-Rho-containing patches
      throughout the cell cortex. Similarly, in dividing cells, a structure composed of
      Rho and Citron-K in cleavage furrow excludes cortical actin cytoskeleton, and
      disruption of F-actin disperses Citron-K throughout the cell cortex. These
      results suggest that Citron-K is a novel type of a passenger protein, which is
      dispersed to the cytoplasm in prometaphase and associated with midzone spindles
      by a Rho-independent signal. Rho is then activated, binds to Citron-K and
      translocates it to cell cortex, where the complex is then concentrated in the
      cleavage furrow by the action of actin cytoskeleton beneath the equator of
      dividing cells.

PMID- 11591817
TI  - Focal adhesion features during myofibroblastic differentiation are controlled by
      intracellular and extracellular factors.
AB  - Transforming growth factor beta (TGFbeta), the most established promoter of
      myofibroblast differentiation, induces ED-A cellular fibronectin and alpha-smooth
      muscle actin expression in fibroblastic cells in vivo and in vitro. ED-A
      fibronectin exerts a permissive action for alpha-smooth muscle actin expression.
      A morphological continuity (called fibronexus), a specialized form of focal
      adhesion, has been described between actin stress fibers that contain alpha
      smooth muscle actin, and extracellular fibronectin, which contains the ED-A
      portion, in both cultured fibroblasts and granulation tissue myofibroblasts. We
      have studied the development of these focal adhesions in TGFbeta-treated
      fibroblasts using confocal laser scanning microscopy, three-dimensional image
      reconstruction and western blots using antibodies against focal adhesion
      proteins. The increase in ED-A fibronectin expression induced by TGFbeta was
      accompanied by bundling of ED-A fibronectin fibers and their association with the
      terminal portion of alpha-smooth muscle actin-positive stress fibers. In
      parallel, the focal adhesion size was importantly increased, and tensin and FAK
      were neoexpressed in focal adhesions; moreover, vinculin and paxillin were
      recruited from the cytoplasmic pool into focal adhesions. We have evaluated
      morphometrically the length and area of focal adhesions. In addition, we have
      evaluated biochemically their content of associated proteins and of alpha-smooth
      muscle actin after TGFbeta stimulation and on this basis suggest a new focal
      adhesion classification, that is, immature, mature and supermature. When TGFbeta
      induced alpha-smooth muscle actin expression was blocked by soluble recombinant
      ED-A fibronectin, we observed that the fragment was localised into the
      fibronectin network at the level of focal adhesions and that focal adhesion
      supermaturation was inhibited. The same effect was also exerted by the ED-A
      fibronectin antibody IST-9. In addition, the antagonists of actin-myosin
      contractility BDM and ML-7 provoked the dispersion of focal adhesions and the
      decrease of alpha-smooth muscle actin content in stress fibers of pulmonary
      fibroblasts, which constitutively show large focal adhesions and numerous stress
      fibers that contain alpha-smooth muscle actin. These inhibitors also decreased
      the incorporation of recombinant ED-A into fibronectin network. Our data indicate
      that a three-dimensional transcellular structure containing both ED-A fibronectin
      and alpha-smooth muscle actin plays an important role in the establishment and
      modulation of the myofibroblastic phenotype. The organisation of this structure
      is regulated by intracellularly and extracellularly originated forces.

PMID- 11591818
TI  - Nuclear membrane protein LAP2beta mediates transcriptional repression alone and
      together with its binding partner GCL (germ-cell-less).
AB  - LAP2beta is an integral membrane protein of the nuclear envelope involved in
      chromatin and nuclear architecture. Using the yeast two-hybrid system, we have
      cloned a novel LAP2beta-binding protein, mGCL, which contains a BTB/POZ domain
      and is the mouse homologue of the Drosophila germ-cell-less (GCL) protein. In
      Drosophila embryos, GCL was shown to be essential for germ cell formation and was
      localized to the nuclear envelope. Here, we show that, in mammalian cells, GCL is
      co-localized with LAP2beta to the nuclear envelope. Nuclear fractionation studies
      reveal that mGCL acts as a nuclear matrix component and not as an integral
      protein of the nuclear envelope. Recently, mGCL was found to interact with the
      DP3alpha component of the E2F transcription factor. This interaction reduced the
      transcriptional activity of the E2F-DP heterodimer, probably by anchoring the
      complex to the nuclear envelope. We demonstrate here that LAP2beta is also
      capable of reducing the transcriptional activity of the E2F-DP complex and that
      it is more potent than mGCL in doing so. Co-expression of both LAP2beta and mGCL
      with the E2F-DP complex resulted in a reduced transcriptional activity equal to
      that exerted by the pRb protein.

PMID- 11591819
TI  - Brefeldin A rapidly disrupts plasma membrane polarity by blocking polar sorting
      in common endosomes of MDCK cells.
AB  - Recent studies showing thorough intermixing of apical and basolateral endosomes
      have demonstrated that endocytic sorting is critical to maintaining the plasma
      membrane polarity of epithelial cells. Our studies of living, polarized cells
      show that disrupting endocytosis with brefeldin-A rapidly destroys the polarity
      of transferrin receptors in MDCK cells while having no effect on tight junctions.
      Brefeldin-A treatment induces tubulation of endosomes, but the sequential
      compartments and transport steps of the transcytotic pathway remain intact.
      Transferrin is sorted from LDL, but is then missorted from common endosomes to
      the apical recycling endosome, as identified by its nearly neutral pH, and
      association with GFP chimeras of Rabs 11a and 25. From the apical recycling
      endosome, transferrin is then directed to the apical plasma membrane. These data
      are consistent with a model in which polarized sorting of basolateral membrane
      proteins occurs via a brefeldin-A-sensitive process of segregation into
      basolateral recycling vesicles. Although disruption of polar sorting correlates
      with dissociation of gamma-adaptin from endosomes, gamma-adaptin does not appear
      to be specifically involved in sorting into recycling vesicles, as we find it
      associated with the transcytotic pathway, and particularly to the post-sorting
      transcytotic apical recycling endosome.

PMID- 11591820
TI  - Syntaxin 1A is delivered to the apical and basolateral domains of epithelial
      cells: the role of munc-18 proteins.
AB  - SNARE (Soluble N-ethyl-maleimide sensitive factor Attachment protein Receptor)
      proteins assemble in tight core complexes, which promote fusion of carrier
      vesicles with target compartments. Members of this class of proteins are
      expressed in all eukaryotic cells and are distributed in distinct subcellular
      compartments. The molecular mechanisms underlying sorting of SNAREs to their
      physiological sites of action are still poorly understood. Here have we analyzed
      the transport of syntaxin1A in epithelial cells. In line with previous data we
      found that syntaxin1A is not transported to the plasma membrane, but rather is
      retained intracellularly when overexpressed in MDCK and Caco-2 cells. Its
      delivery to the cell surface is recovered after munc-18-1 cotransfection.
      Furthermore, overexpression of the ubiquitous isoform of munc-18, munc-18-2, is
      also capable of rescuing the transport of the t-SNARE. The interaction between
      syntaxin 1A and munc-18 occurs in the biosynthetic pathway and is required to
      promote the exit of the t-SNARE from the Golgi complex. This enabled us to
      investigate the targeting of syntaxin1A in polarized cells. Confocal analysis of
      polarized monolayers demonstrates that syntaxin1A is delivered to both the apical
      and basolateral domains independently of the munc-18 proteins used in the
      cotranfection experiments. In search of the mechanisms underlying syntaxin 1A
      sorting to the cell surface, we found that a portion of the protein is included
      in non-ionic detergent insoluble complexes. Our results indicate that the munc-18
      proteins represent limiting but essential factors in the transport of syntaxin1A
      from the Golgi complex to the epithelial cell surface. They also suggest the
      presence of codominant apical and basolateral sorting signals in the syntaxin1A
      sequence.

PMID- 11591821
TI  - Phagocytosis mediated by Yersinia invasin induces collagenase-1 expression in
      rabbit synovial fibroblasts through a proinflammatory cascade.
AB  - We show that the interaction of the Yersinia surface protein, invasin, with
      rabbit synovial fibroblasts mediates bead phagocytosis and induces expression of
      interleukin 1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha) and MMP
      1/collagenase-1 (CL-1). Presentation of invasin as a ligand on the surface of 4.5
      microm beads induced phagocytosis and increased CL-1 expression 20-fold after 24
      hours. By contrast, presentation of invasin as a spreading substrate did not
      induce CL-1 expression. CL-1 induction following phagocytosis of invasin-coated
      beads was mediated by a mechanism dependent on high-affinity binding to beta1
      integrins and the function of the small GTPase RhoA. Expression of a function
      perturbing mutant, RhoAN19, abrogated bead-induced CL-1 expression. RhoA
      activation coupled bead phagocytosis with signal transduction because expression
      of constitutively active mutant RhoV14 was sufficient to trigger CL-1 expression.
      The signal-transduction cascade elicited by bead phagocytosis triggered NFkappaB
      activation, stimulating a proinflammatory cellular response with transient
      increases in TNF-alpha production that peaked at 2 hours and induction of IL
      1alpha that was sustained for at least 10 hours. Inhibition of IL-1alpha function
      by blocking antibodies or IL-1 receptor antagonist showed that IL-1alpha is the
      autocrine intermediary for subsequent CL-1 induction.

PMID- 11591822
TI  - DNA double-strand breaks induce formation of RP-A/Ku foci on in vitro
      reconstituted Xenopus sperm nuclei.
AB  - Replication protein A (RP-A) is involved in DNA replication, repair and
      recombination. It has been demonstrated that RP-A clusters in foci prior to DNA
      replication and redistributes over chromatin during S-phase. Here, we show that
      RP-A foci also form in response to DNA double-strand (ds) breaks produced on
      Xenopus laevis sperm nuclei by restriction enzymes and then reconstituted with
      Xenopus egg high-speed extracts. Ku86 co-localizes with RP-A in the same foci. An
      unscheduled RP-A-dependent DNA synthesis takes place overlapping with RP-A and
      Ku86 foci. Immunoelectron-microscopy analysis reveals that these foci correspond
      to spherical bodies up to 300 nm in diameter, which contain RP-A, Ku86 and DNA.
      In an independent in vitro assay, we incubated linear dsDNA bound to magnetic
      beads with Xenopus egg extracts. Here, also RP-A and Ku cluster in foci as seen
      through immunofluorescence. Both proteins appear to enrich themselves in
      sequences near the ends of the DNA molecules and influence ligation efficiency of
      ds linear DNA to these ends. Thus, the Xenopus in vitro system allows for the
      generation of specific DNA ds breaks, RP-A and Ku can be used as markers for
      these lesions and the repair of this type of DNA damage can be studied under
      conditions of a normal nuclear environment.

PMID- 11591823
TI  - FGF signalling is required for differentiation-induced cytoskeletal
      reorganisation and formation of actin-based processes by podocytes.
AB  - To examine the potential role of fibroblast growth factor (FGF) signalling during
      cell differentiation, we used conditionally immortalised podocyte cells isolated
      from kidneys of Fgf2 mutant and wild-type mice. Wild-type mouse podocyte cells
      upregulate FGF2 expression when differentiating in culture, as do maturing
      podocytes in vivo. Differentiating wild-type mouse podocyte cells undergo an
      epithelial to mesenchymal-like transition, reorganise their actin cytoskeleton
      and extend actin-based cellular processes; all of these activities are similar to
      the activity of podocytes in vivo. Molecular analysis of Fgf2 mutant mouse
      podocyte cells reveals a general disruption of FGF signalling as expression of
      Fgf7 and Fgf10 are also downregulated. These FGF mutant mouse podocyte cells in
      culture fail to activate mesenchymal markers and their post-mitotic
      differentiation is blocked. Furthermore, mutant mouse podocyte cells in culture
      fail to reorganise their actin cytoskeleton and form actin-based cellular
      processes. These studies show that FGF signalling is required by cultured
      podocytes to undergo the epithelial to mesenchymal-like changes necessary for
      terminal differentiation. Together with other studies, these results point to a
      general role for FGF signalling in regulating cell differentiation and formation
      of actin-based cellular processes during morphogenesis.

PMID- 11591824
TI  - M31 and macroH2A1.2 colocalise at the pseudoautosomal region during mouse
      meiosis.
AB  - Progression through meiotic prophase is associated with dramatic changes in
      chromosome condensation. Two proteins that have been implicated in effecting
      these changes are the mammalian HP1-like protein M31 (HP1beta or MOD1) and the
      unusual core histone macroH2A1.2. Previous analyses of M31 and macroH2A1.2
      localisation in mouse testis sections have indicated that both proteins are
      components of meiotic centromeric heterochromatin and of the sex body, the
      transcriptionally inactive domain of the X and Y chromosomes. This second
      observation has raised the possibility that these proteins co-operate in meiotic
      sex chromosome inactivation. In order to investigate the roles of M31 and
      macroH2A1.2 in meiosis in greater detail, we have examined their localisation
      patterns in surface-spread meiocytes from male and female mice. Using this
      approach, we report that, in addition to their previous described staining
      patterns, both proteins localise to a focus within the portion of the
      pseudoautosomal region (PAR) that contains the steroid sulphatase (Sts) gene. In
      light of the timing of its appearance and of its behaviour in sex-chromosomally
      variant mice, we suggest a role for this heterochromatin focus in preventing
      complete desynapsis of the terminally associated X and Y chromosomes prior to
      anaphase I.

PMID- 11591825
TI  - Evidence for a role for a Plasmodium falciparum homologue of Sec31p in the export
      of proteins to the surface of malaria parasite-infected erythrocytes.
AB  - The malaria parasite, Plasmodium falciparum, spends part of its life cycle inside
      the enucleated erythrocytes of its human host. The parasite modifies the
      cytoplasm and plasma membrane of its host cell by exporting proteins beyond the
      confines of its own plasma membrane. We have previously provided evidence that a
      plasmodial homologue of the COPII protein, Sar1p, is involved in the trafficking
      of proteins across the erythrocyte cytoplasm. We have now characterised an
      additional plasmodial COPII protein homologue, namely Sec31p. Recombinant
      proteins corresponding to the WD-40 and the intervening domains of the PfSec31p
      sequence were used to raise antibodies. The affinity-purified antisera recognised
      a protein with an apparent relative molecular mass of 1.6 x 10(5) on western
      blots of malaria parasite-infected erythrocytes but not on blots of uninfected
      erythrocytes. PfSec31p was shown to be largely insoluble in nonionic detergent,
      suggesting cytoskeletal attachment. Confocal immunofluorescence microscopy of
      malaria parasite-infected erythrocytes was used to show that PfSec31p is partly
      located within the parasite and partly exported to structures outside the
      parasite in the erythrocyte cytoplasm. We have also shown that PfSec31p and
      PfSar1p occupy overlapping locations. Furthermore, the location of PfSec31p
      overlaps that of the cytoadherence-mediating protein PfEMP1. These data support
      the suggestion that the malaria parasite establishes a vesicle-mediated
      trafficking pathway outside the boundaries of its own plasma membrane - a novel
      paradigm in eukaryotic biology.

PMID- 11591826
TI  - Endogenously produced urokinase-type plasminogen activator is a major determinant
      of the basal level of activated ERK/MAP kinase and prevents apoptosis in MDA-MB
      231 breast cancer cells.
AB  - Urokinase-type plasminogen activator (uPA) binds to the uPA receptor (uPAR) and
      activates the Ras-extracellular signal-regulated kinase (ERK) signaling pathway
      in many different cell types. In this study, we demonstrated that endogenously
      produced uPA functions as a major determinant of the basal level of activated ERK
      in MDA-MB-231 breast cancer cells. When these cells were cultured in the presence
      of antibodies that block the binding of uPA to uPAR, the level of phosphorylated
      ERK decreased substantially. Furthermore, conditioned medium from MDA-MB-231
      cells activated ERK in MCF-7 cells and this response was blocked by uPA-specific
      antibody. The mitogen-activated protein kinase kinase inhibitor, PD098059,
      decreased expression of uPA and uPAR in MDA-MB-231 cells. Thus, uPA and the uPAR
      ERK signaling pathway form a positive feedback loop in these cells. When this
      feedback loop was disrupted with uPA- or uPAR-specific antibody, uPA mRNA
      specific antisense oligodeoxynucleotides or PD098059, cell growth was inhibited
      and apoptosis was promoted, as determined by the increase in cytoplasmic
      nucleosomes and caspase-3 activity. Treating the cells simultaneously with
      PD098059 and uPA- or uPAR-specific antibody did not further promote apoptosis,
      compared with either reagent added separately, supporting the hypothesis that
      uPAR and ERK are components of the same cell growth/survival-regulatory pathway.
      The ability of uPA to signal through uPAR, maintain an elevated basal level of
      activated ERK and inhibit apoptosis represents a novel mechanism whereby the uPA
      uPAR system may affect breast cancer progression in vivo.

PMID- 11591827
TI  - Inactivation of the checkpoint kinase Cds1 is dependent on cyclin B-Cdc2 kinase
      activation at the meiotic G(2)/M-phase transition in Xenopus oocytes.
AB  - Checkpoint controls ensure chromosomal integrity through the cell cycle. Chk1 and
      Cds1/Chk2 are effector kinases in the G(2)-phase checkpoint activated by damaged
      or unreplicated DNA, and they prevent entry into M-phase through inhibition of
      cyclin B-Cdc2 kinase activation. However, little is known about how the effector
      kinases are regulated when the checkpoint is attenuated. Recent studies indicate
      that Chk1 is also involved in the physiological G(2)-phase arrest of immature
      Xenopus oocytes via direct phosphorylation and inhibition of Cdc25C, the
      activator of cyclin B-Cdc2 kinase. Bearing in mind the overlapping functions of
      Chk1 and Cds1, here we have studied the involvement of Xenopus Cds1 (XCds1) in
      the G(2)/M-phase transition of immature oocytes and the regulation of its
      activity during this period. Protein levels of XCds1 remained constant throughout
      oocyte maturation and early embryonic development. The levels of XCds1 kinase
      activity were high in immature oocytes and decreased at the meiotic G(2)/M-phase
      transition. Consistently, when overexpressed in immature oocytes, wild-type, but
      not kinase-deficient, XCds1 significantly delayed entry into M-phase after
      progesterone treatment. The inactivation of XCds1 depended on the activation of
      cyclin B-Cdc2 kinase, but not MAP kinase. Although XCds1 was not directly
      inactivated by cyclin B-Cdc2 kinase in vitro, XCds1 was inactivated by
      overexpression of cyclin B, which induces the activation of cyclin B-Cdc2 kinase
      without progesterone. Thus, the present study is the first indication of Cds1
      activity in cells that are physiologically arrested at G(2)-phase, and of its
      downregulation at entry into M-phase.

PMID- 11591828
TI  - Face module, face network: The cognitive architecture of the brain revealed
      through studies of face processing.

PMID- 11591829
TI  - Genetic association studies: genes in search of diseases.

PMID- 11591830
TI  - Covert recognition in acquired and developmental prosopagnosia.
AB  - BACKGROUND: Some patients with prosopagnosia have covert recognition, meaning
      that they retain some familiarity or knowledge of facial identity of which they
      are not aware. OBJECTIVE: To test the hypothesis that prosopagnosic patients with
      right occipitotemporal lesions and impaired face perception lack covert
      processing, whereas patients with associative prosopagnosia and bilateral
      anterior temporal lesions possess it. METHODS: Eight patients with prosopagnosia
      were tested with a battery of four face recognition tests to determine their
      ability to discriminate between famous and unknown faces. RESULTS: Measures of
      overt familiarity revealed better residual discrimination in patients with
      acquired prosopagnosia than in those with the developmental form. With forced
      choice methods using famous faces paired with unknown faces, no patient
      demonstrated covert familiarity. However, when the semantic cue of the name of
      the famous face was provided, covert processing was present in all five patients
      with acquired prosopagnosia, including the three with extensive right-sided
      lesions and impaired perceptual discrimination of facial configuration. Sorting
      unrecognized faces by occupation was also performed above chance in three of
      these five patients. In contrast, none of the three patients with developmental
      prosopagnosia had covert processing, even though two demonstrated flawless
      performance on similar tests of name (rather than face) recognition. Overt
      familiarity correlated highly with the degree of covert recognition. CONCLUSIONS:
      Extensive right occipitotemporal lesions with significant deficits in face
      perception are not incompatible with covert face processing. Covert processing is
      absent in developmental prosopagnosia, because this condition likely precludes
      the establishment of a store of accurate facial memories. The presence of covert
      processing correlates with the degree of residual overt familiarity, indicating
      that these are related phenomena.

PMID- 11591831
TI  - Face memory impairments in patients with frontal lobe damage.
AB  - OBJECTIVE: To determine whether damage to prefrontal cortex is associated with
      face memory impairment. BACKGROUND: Neurophysiologic and functional imaging
      studies suggest that prefrontal cortex is a key component of a distributed neural
      network that mediates face recognition memory. However, there have been few
      attempts to examine the impact of frontal lobe damage on face memory performance.
      METHODS: Patients with focal frontal lobe lesions and normal control subjects
      were administered two-alternative forced-choice and single-probe "yes/no" tests
      of recognition memory for novel faces. Retrograde memory was assessed by using
      famous faces as stimuli. RESULTS: Compared with control subjects, patients with
      frontal lobe lesions showed evidence of marked anterograde and relatively mild
      retrograde face memory impairment. In addition, patients with right frontal
      lesions demonstrated increased susceptibility to false recognition, consistent
      with the breakdown of strategic memory retrieval, monitoring, and decision
      functions. CONCLUSIONS: Prefrontal cortex plays an important role in the
      executive control of face memory encoding and retrieval. Left and right
      prefrontal regions seem to make different contributions to recognition memory
      performance.

PMID- 11591832
TI  - Serial EEG during human status epilepticus: evidence for PLED as an ictal
      pattern.
AB  - OBJECTIVE: To analyze the relationship between periodic lateralized epileptiform
      discharges (PLED) and status epilepticus (SE), to evaluate the relationship
      between mortality and periodic patterns, and to determine whether a stereotypic
      sequence of EEG patterns exists during human SE. METHODS: The authors performed a
      prospective clinical and electrographic study comprising 62 episodes of SE, 55
      patients, and 254 ictal/postictal EEG recordings. Serial daily EEG were obtained
      in all cases. RESULTS: Partial SE was the predominant clinical type. Four
      distinct ictal EEG patterns were identified: intermittent EEG seizures (IES),
      merging EEG seizures (MES), continuous ictal discharges (CID), and periodic
      epileptiform discharges (PED) which could be lateralized (PLED) or bilateral
      (PBED). IES was the most common ictal pattern. In the same record, only one
      combination of ictal patterns was observed corresponding to an association of
      PLED or PBED and MES pattern. Serial EEG demonstrated that approximately one
      third of SE resolved before the second EEG, another one-third persisted and
      maintained the same ictal pattern throughout the entire evolution, and the final
      one-third showed variable ictal EEG patterns. PLED were also unequivocally
      associated with epileptic seizures, and in some patients were the initial ictal
      pattern. CONCLUSION: PLED can be an ictal pattern; and, in contrast to previous
      observations, no stereotyped sequence of ictal EEG patterns was found. PLED/PBED
      were not a terminal ictal pattern in every case, and outcome was more related to
      age and etiology than to specific ictal EEG patterns.

PMID- 11591833
TI  - In vivo hippocampal glucose metabolism in mesial temporal lobe epilepsy.
AB  - BACKGROUND: The appearance of decreased 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG)
      uptake in the mesial temporal region in temporal lobe epilepsy may simply reflect
      loss of gray matter due to hippocampal atrophy. Increased partial volume effects
      due to atrophic hippocampi may further increase appearance of hypometabolism.
      METHODS: The authors used a combination of MRI-PET coregistration, with MRI-based
      gray matter segmentation, and partial volume correction to improve the
      examination of hippocampal specific glucose uptake in FDG PET. The goal was to
      determine 1) if relative mesial temporal hypometabolism is an artifact of gray
      matter (hippocampal) atrophy, 2) whether hippocampal metabolism correlates with
      atrophy evaluated on MRI, and 3) if MRI-based partial volume correction
      influences measurement of hippocampal metabolic-volume relationships, including
      epilepsy lateralization. RESULTS: Findings showed that ipsilateral hippocampi of
      mesial temporal lobe epilepsy (MTLE) are relatively hypometabolic per unit of
      gray matter volume, and that hippocampal metabolism directly correlates with
      hippocampal volume. Specifically, partial volume corrected hippocampal metabolism
      correlated strongly (r = 0.613, p < 0.001) with hippocampal volume. Without
      partial volume correction, a weaker, but still significant, correlation was
      present (r = 0.482, p < 0.001). Degree of asymmetry was consistently greater and
      provided higher sensitivity of lateralization with partial volume vs non-partial
      volume corrected metabolic measurements. CONCLUSIONS: Although, decreased
      metabolism may occur in the absence of neuronal cell loss, hippocampal atrophy
      and presumed degree of neuronal cell loss appears to be a primary factor involved
      in the cause of decreased metabolism in epileptogenic hippocampi. Partial volume
      correction is recommended for optimal interpretation of hippocampal structure and
      function relationships.

PMID- 11591834
TI  - Generalized epilepsy with febrile seizures plus: further heterogeneity in a large
      family.
AB  - BACKGROUND: Generalized epilepsy with febrile seizures plus (GEFS(+)) is a
      recently described benign childhood-onset epileptic syndrome with autosomal
      dominant inheritance. The most common phenotypes are febrile seizures (FS) often
      with accessory afebrile generalized tonic-clonic seizures (GTCS, FS(+)). In about
      one third, additional seizure types occur, such as absences, myoclonic, or atonic
      seizures. So far, three mutations within genes encoding subunits of neuronal
      voltage-gated Na(+) channels have been found in GEFS(+) families, one in SCN1B
      (beta(1)-subunit) and two in SCN1A (alpha-subunit). METHODS: The authors examined
      the phenotypic variability of GEFS(+) in a five-generation German family with 18
      affected individuals. Genetic linkage analysis was performed to exclude candidate
      loci. RESULTS: Inheritance was autosomal dominant with a penetrance of about 80%.
      A variety of epilepsy phenotypes occurred predominantly during childhood. Only
      four individuals showed the FS or FS(+) phenotype. The others presented with
      different combinations of GTCS, tonic seizures, atonic seizures, and absences,
      only in part associated with fever. The age at onset was 2.8 +/- 1.3 years.
      Interictal EEG recordings showed rare, 1- to 2-second-long generalized, irregular
      spike-and-wave discharges of 2.5 to 5 Hz in eight cases and additional focal
      parietal discharges in one case. Linkage analysis excluded the previously
      described loci on chromosomes 2q21-33 and 19q13. All other chromosomal regions
      containing known genes encoding neuronal Na(+) channel subunits on chromosomes
      3p21-24, 11q23, and 12q13 and described loci for febrile convulsions on
      chromosomes 5q14-15, 8q13-21, and 19p13.3 were also excluded. CONCLUSION: These
      results indicate further clinical and genetic heterogeneity in GEFS(+).

PMID- 11591835
TI  - The Clomethiazole Acute Stroke Study in tissue-type plasminogen activator-treated
      stroke (CLASS-T): final results.
AB  - OBJECTIVE: To assess the safety of tissue-type plasminogen activator (t-PA) plus
      clomethiazole in patients with acute ischemic stroke and determine the
      feasibility of combination stroke therapy. BACKGROUND: Clomethiazole is a
      neuroprotectant that appeared to improve outcome in patients with clinical
      deficits of a major stroke (total anterior circulation syndrome [TACS]) in a
      previous study, the Clomethiazole Acute Stroke Study (CLASS). Combining a
      neuroprotectant such as clomethiazole with thrombolysis may augment the
      beneficial effects of the two agents. CLASS-t-PA (CLASS-T) was a pilot study to
      explore the safety of the combination and the feasibility of performing
      combination treatment in the setting of acute ischemic stroke. METHODS: In a
      randomized, double-blind design (stratified for age, severity at admission, and
      time since onset of stroke), all patients received 0.9 mg/kg t-PA beginning
      within 3 hours of stroke onset and then either 68 mg/kg clomethiazole (n = 97) IV
      over 24 hours or placebo (n = 93) beginning within 12 hours of stroke onset.
      Patients were followed for 90 days. The main measures of safety were mortality
      and serious adverse events, and the main measure of functional outcome was the
      Barthel Index. RESULTS: The number of serious adverse event reports was 47 in the
      clomethiazole group and 48 in the placebo group. Death during the 90 days after
      treatment occurred in 15 clomethiazole and nine placebo patients (p = 0.26).
      Sedation was reported as an adverse event during therapy in 42% of clomethiazole
      patients vs 13% of placebo patients. The proportion of patients with TACS was 53%
      in the clomethiazole group and 41% in the placebo group. In the TACS subgroup,
      52.9% of the clomethiazole patients scored a Barthel Index greater than 60 vs
      44.7% of placebo patients (odds ratio 1.39; 95% CI 0.60 to 3.23). CONCLUSION: In
      this pilot study, there were no safety concerns related to the combination of t
      PA and clomethiazole. The combination paradigm proved feasible, although many
      patients received clomethiazole several hours after thrombolysis; future studies
      must require prompt administration of the neuroprotectant either before or during
      administration of the thrombolytic. Patients with major strokes (TACS) may have
      the potential to benefit from the combination of t-PA and clomethiazole.

PMID- 11591836
TI  - Relationship between severity of MR perfusion deficit and DWI lesion evolution.
AB  - OBJECTIVE: To assess whether a quantitative analysis of the severity of the early
      perfusion deficit on MRI in acute ischemic stroke predicts the evolution of the
      perfusion/diffusion mismatch and to determine thresholds of hypoperfusion that
      can distinguish between critical and noncritical hypoperfusion. METHODS: Patients
      with acute ischemic stroke were studied in whom perfusion-weighted imaging (PWI)
      and diffusion-weighted imaging (DWI MRI) were performed within 7 hours of symptom
      onset and again after 4 to 7 days. Patients with early important decreases in
      points on the NIH Stroke Scale were excluded. Maps of cerebral blood flow (CBF),
      cerebral blood volume (CBV), and mean transit time (MTT) were created. These
      hemodynamic parameters were correlated with the degree of recruitment of the
      baseline PWI lesion by the DWI lesion. RESULTS: Twelve patients had an initial
      PWI > DWI mismatch of >20%. A linear relationship was observed between the
      initial MTT and the degree of recruitment of the baseline PWI lesion by the DWI
      lesion at follow-up (R(2) = 0.9, p < 0.001). Higher CBV values were associated
      with higher degrees of recruitment (rho = 0.732, p < 0.007). The volume of MTT of
      >4 (R(2) = 0.86, p < 0.001) or >6 seconds (R(2) = 0.85, p < 0.001) predicted
      final infarct size. CONCLUSION: Among patients who have had an acute stroke with
      PWI > DWI, who do not have dramatic early clinical improvement, the degree of
      expansion of the initial DWI lesion correlates with the severity of the initial
      perfusion deficit as measured by the mean transit time and the cerebral blood
      volume.

PMID- 11591837
TI  - Small cerebral aneurysms presenting with symptoms other than rupture.
AB  - BACKGROUND: Recent natural history studies have suggested that unruptured
      intracranial aneurysms smaller than 1 cm have a low risk of rupture. Symptomatic
      aneurysms may be underrepresented in natural history studies because they are
      preferentially treated. The authors compared the number of patients with symptoms
      caused by unruptured intracranial aneurysms smaller than 1 cm treated surgically
      at their institution with similar patients enrolled in the International Study of
      Unruptured Intracranial Aneurysms (ISUIA) from their institution over the same
      time period. METHODS: The records of all unruptured aneurysms treated surgically
      at the Mayo Clinic from 1980 through 1991 were reviewed. There were 97 patients
      with 117 unruptured aneurysms smaller than 1 cm by angiography. Aneurysms with a
      history of rupture or larger than 1 cm on cross-sectional imaging were excluded
      from analysis. The presence and characteristics of symptoms directly attributable
      to the aneurysm were recorded. Comparison was made with patients from the Mayo
      Clinic enrolled in the ISUIA retrospective natural history cohort over the same
      time period. RESULTS: Of the 97 patients studied, 15 presented with symptoms
      other than rupture (15.5%). The symptoms were third nerve deficit (seven
      patients), cerebral ischemia owing to emboli originating from within the aneurysm
      (five patients), and visual acuity loss (three patients). Eleven other aneurysms
      had possibly but not definitively caused symptoms; these were considered
      asymptomatic. No patient from the Mayo Clinic enrolled in the retrospective
      cohort of the ISUIA had a symptomatic aneurysm smaller than 1 cm on both
      angiography and cross-sectional imaging. CONCLUSIONS: Unruptured intracranial
      aneurysms smaller than 1 cm occasionally present with neurologic symptoms. These
      symptoms are typically owing to mass effect on the second and third cranial
      nerves or cerebral ischemia as a result of emboli originating from within the
      aneurysm. Patients with symptomatic unruptured aneurysms less than 1 cm at the
      Mayo Clinic were preferentially treated. Although existing natural history data
      may be applied to most unruptured aneurysms, small symptomatic aneurysms may be
      underrepresented in natural history studies.

PMID- 11591838
TI  - Poststroke dementia: incidence and relationship to prestroke cognitive decline.
AB  - OBJECTIVE: To evaluate the 3-year incidence of poststroke dementia (PSD) and the
      influence of prestroke cognitive decline. METHODS: The authors evaluated
      prestroke cognitive functions in 202 consecutive stroke patients > or =40 years
      old using the Informant Questionnaire on Cognitive Decline in the Elderly
      (IQCODE), with a cut-off of 104 for the diagnosis of dementia. Six months and
      then annually after stroke, dementia was reassessed. The diagnosis of dementia
      was based on the International Classification of Diseases, 10th revision criteria
      in survivors who underwent a visit with a neurologist, or on the IQCODE score
      obtained by telephone contact with the family in survivors who did not.
      Statistics were performed using life-table methods. RESULTS: Thirty-three
      patients were excluded because of prestroke dementia. In the 169 remaining
      patients, the cumulative proportion of patients with dementia was 28.5% at the
      end of the follow-up period, with most of PSD occurring during the first 6
      months. Using multivariate analysis, independent predictors of PSD were aging,
      preexisting cognitive decline, severity of deficit at admission, diabetes
      mellitus, and silent infarcts. Leukoaraiosis was an independent predictor of PSD
      when prestroke cognitive decline was not taken into account. The presumed
      etiology of dementia was vascular dementia (VaD) in two-thirds of patients and AD
      in one-third. CONCLUSIONS: The risk of PSD is high, and increased in patients
      with prestroke cognitive decline, with about one-third of patients meeting the
      criteria for AD and two-thirds meeting the criteria for VaD. These results
      confirm that, in stroke patients, an underlying degenerative pathology may play a
      role in the development of PSD.

PMID- 11591840
TI  - Silent MRI infarcts and the risk of future stroke: the cardiovascular health
      study.
AB  - BACKGROUND: Silent infarcts are commonly discovered on cranial MRI in the
      elderly. OBJECTIVE: To examine the association between risk of stroke and
      presence of silent infarcts, alone and in combination with other stroke risk
      factors. METHODS: Participants (3,324) in the Cardiovascular Health Study (CHS)
      without a history of stroke underwent cranial MRI scans between 1992 and 1994.
      Silent infarcts were defined as focal lesions greater than 3 mm that were
      hyperintense on T2 images and, if subcortical, hypointense on T1 images. Incident
      strokes were identified and classified over an average follow-up of 4 years. The
      authors evaluated the risk of subsequent symptomatic stroke and how it was
      modified by other potential stroke risk factors among those with silent infarcts.
      RESULTS: Approximately 28% of CHS participants had evidence of silent infarcts (n
      = 923). The incidence of stroke was 18.7 per 1,000 person-years in those with
      silent infarcts (n = 67) compared with 9.5 per 1,000 person-years in the absence
      of silent infarcts. The adjusted relative risk of incident stroke increased with
      multiple (more than one) silent infarcts (hazard ratio 1.9 [1.2 to 2.8]). Higher
      values of diastolic and systolic blood pressure, common and internal carotid wall
      thickness, and the presence of atrial fibrillation were associated with an
      increased risk of strokes in those with silent infarcts (n = 53 strokes).
      CONCLUSION: The presence of silent cerebral infarcts on MRI is an independent
      predictor of the risk of symptomatic stroke over a 4-year follow- up in older
      individuals without a clinical history of stroke.

PMID- 11591841
TI  - Sensory symptoms in ipsilateral limbs/body due to lateral medullary infarction.
AB  - OBJECTIVES: To characterize the incidence, topography, and radiologic and
      pathophysiologic findings of ipsilateral sensory symptoms in the limbs/body in
      patients with lateral medullary infarction. METHOD: Between 1994 and 2001, the
      author identified 12 patients with lateral medullary infarction (6.7% of all
      lateral medullary infarction patients) who presented with ipsilateral sensory
      symptoms in the limbs/body in addition to typical lateral medullary syndrome.
      Brain MRI, nerve conduction velocity, and electromyographic studies were
      performed. Twenty-four patients without ipsilateral sensory symptoms were
      included as a control group. Clinical and radiologic findings were compared
      between the two groups. RESULTS: The ipsilateral sensory symptoms were generally
      described as numbness or tightness, predominantly affecting the upper
      extremities, especially distal fingers. Vibration and proprioceptive sensation
      were occasionally impaired. None showed evidence of peripheral neuropathy or
      radiculopathy. The patients with ipsilateral sensory symptoms significantly more
      often had vertigo, nausea/vomiting, severe gait ataxia, hiccup, ipsilateral
      hemiparesis, and caudally located lesions than those without. The caudal lesions
      producing ipsilateral sensory symptoms tended to extend dorsomedially.
      CONCLUSION: Lateral medullary infarction associated with ipsilateral sensory
      symptoms in the limbs/body is an uncommon but distinct variant caused by caudal
      lesions extending dorsomedially that probably involve the ipsilateral dorsal
      column or decussating lemniscal fibers.

PMID- 11591842
TI  - Mitochondrial dysfunction associated with a mutation in the Notch3 gene in a
      CADASIL family.
AB  - BACKGROUND: Cerebral autosomal arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is characterized by recurrent subcortical ischemic
      strokes and dementia caused by mutations in the Notch3 gene. In Drosophila
      melanogaster, Notch signaling has a pleiotropic effect, affecting most tissues of
      the organism during development. OBJECTIVE: To characterize a potential
      mitochondrial dysfunction associated with mutations in the Notch3 gene. METHODS:
      Biochemical, histochemical, molecular, and genetic analyses were performed on
      muscle biopsy specimens and fibroblasts obtained from patients of a Spanish
      family with CADASIL. Additional biochemical and molecular analyses of the
      N(55e11) mutant of D. melanogaster were performed. RESULTS: In muscle biopsy
      specimens, a significant decrease was found in the activity of complex I (NADH
      [reduced form of nicotinamide adenine dinucleotide] dehydrogenase), and in one
      patient, histochemical analysis showed the presence of ragged-red fibers with
      abnormal cytochrome c oxidase staining. Reduced fibroblast activity of complex V
      (ATP synthase) was found. Supporting data on patients with CADASIL, it was found
      that the mutation N(55e11) in Drosophila decreases the activity of mitochondrial
      respiratory complexes I and V. CONCLUSIONS: Mitochondrial respiratory chain
      activity responds, directly or indirectly, to the Notch signaling pathway.
      Mitochondrial dysfunction in patients with CADASIL may be an epiphenomenon, but
      results of this study suggest that the pathophysiology of the disease could
      include a defect in oxidative phosphorylation.

PMID- 11591843
TI  - Effects of IV methylprednisolone on brain atrophy in relapsing-remitting MS.
AB  - BACKGROUND: IV methylprednisolone (IVMP) has been used to treat relapses in
      patients with relapsing-remitting (RR) MS, but its effect on disease progression
      is not known. Furthermore, there are no data on the impact of IVMP on T1 black
      holes or whole-brain atrophy. OBJECTIVE: To determine the effect of IVMP on MRI
      measures of the destructive pathology in patients with RR-MS and secondarily to
      determine the effect of IVMP on disability progression in patients with RR-MS.
      METHODS: The authors conducted a randomized, controlled, single-blind, phase II
      clinical trial of IVMP in patients with RR-MS. Eighty-eight patients with RR-MS
      with baseline Expanded Disability Status Scale (EDSS) scores of < or =5.5 were
      randomly assigned to regular pulses of IVMP (1 g/day for 5 days with an oral
      prednisone taper) or IVMP at the same dose schedule only for relapses (IVMP for
      relapses) and followed without other disease-modifying drug therapy for 5 years.
      Pulsed IVMP was given every 4 months for 3 years and then every 6 months for the
      subsequent 2 years. Patients had quantitative cranial MRI scans at study entry
      and after 5 years and standardized clinical assessments every 4 to 6 months.
      RESULTS: Eighty-one of 88 patients completed the trial as planned, and treatment
      was well tolerated. Baseline demographic, clinical, and MRI measures were well
      matched in the two study arms. Patients on the pulsed IVMP arm received more MP
      than patients on the control arm of the study (p < 0.0001). Mean change in T1
      black hole volume favored pulsed IVMP therapy (+1.3 vs +5.2 mL; p < 0.0001), as
      did mean change in brain parenchymal volume (+2.6 vs -74.5 mL; p = 0.003). There
      was no significant difference between treatment arms in the change in T2 volume
      or annual relapse rate during the study. However, there was significantly more
      EDSS score worsening in the control group, receiving IVMP only for relapses.
      There was a 32.2% reduction (p </= 0.0001) in the probability of sustained EDSS
      score worsening in the pulsed MP arm compared with the relapse treatment arm. At
      the end of the study, EDSS was better in the pulsed MP group (1.7 vs 3.4; p <
      0.0001). Prolonged treatment with pulsed IVMP was safe and well tolerated; only
      two patients dropped out for toxic side effects over 5 years. CONCLUSIONS: In
      patients with RR-MS, treatment with pulses of IVMP slows development of T1 black
      holes, prevents or delays whole-brain atrophy, and prevents or delays disability
      progression. A phase III study of IVMP pulses is warranted.

PMID- 11591844
TI  - Axonal loss in normal-appearing white matter in a patient with acute MS.
AB  - BACKGROUND: Brain imaging studies detect abnormalities in normal-appearing white
      matter in patients with MS. OBJECTIVE: To investigate the histopathologic basis
      for these changes in autopsy tissue from a patient with MS with 9 months' disease
      duration and a terminal brain stem lesion. METHODS: The brain stem and spinal
      cord were analyzed ultrastructurally and immunocytochemically for axons, myelin,
      and activated microglia/macrophages. RESULTS: Pathologic findings were consistent
      with a terminal inflammatory demyelinated lesion at the cervicomedullary
      junction. The ventral spinal cord column, containing descending tracts, exhibited
      22% axonal loss at segment C7, but grossly normal immunostaining for myelin.
      Confocal and electron microscopy revealed myelin sheaths without axonal content
      and initial stages of myelin degradation by activated microglia/macrophages among
      intact myelinated axons. Axonal number and appearance was normal in ascending
      sensory tracts. CONCLUSIONS: These studies confirm axonal degeneration in the
      absence of myelin loss as one histopathologic correlate to abnormal MR findings
      in patients with MS.

PMID- 11591845
TI  - Optimizing the association between disability and biological markers in MS.
AB  - OBJECTIVE: Axonal damage is an important feature of MS pathology and the likely
      substrate of development of progressive disability. Brain volume measurement on
      MRI can be used as an overall marker of tissue damage and axonal loss. The
      authors studied the relation of brain volume measurements with the MS Functional
      Composite (MSFC) in an attempt to improve the clinico-radiologic association.
      METHODS: In 137 patients with MS (80 relapsing-remitting [RR], 36 secondary
      progressive [SP], and 21 primary progressive [PP]) and 12 healthy controls, a
      brain MRI scan was obtained. Patients also underwent MSFC and Expanded Disability
      Status Scale (EDSS) assessments. MRI analysis included determination of
      hypointense T1- and hyperintense T2-weighted lesion load, and two brain volume
      measurements: 1) the parenchymal fraction (PF): whole brain
      parenchyma/intracranial volume; and 2) the ventricular fraction (VF): ventricular
      volume/whole brain parenchyma. RESULTS: The median PF was smaller and the median
      VF larger in the patient group (0.81 for PF and 0.029 for VF) than in the control
      group (0.87 for PF, p < 0.001; and 0.013 for VF, p < 0.01). For the patient
      population, moderate correlations were found between brain volume measurements
      and MSFC (0.36 for PF and -0.40 for VF). Patients with short disease duration
      showed a correlation of MSFC with both brain and lesion volume measurements on
      MRI, whereas patients with long disease duration only showed a correlation with
      brain volume measurements. CONCLUSION: Brain volume measurements are correlated
      with disability as assessed by the MSFC. Although in the early phase of the
      disease the amount of focal demyelination is important, the residual brain volume
      seems to be more relevant in determining disability in later phases of the
      disease.

PMID- 11591846
TI  - Neural and cognitive bases of upper limb apraxia in corticobasal degeneration.
AB  - OBJECTIVE: To investigate the neural and cognitive bases of upper limb apraxia in
      corticobasal degeneration (CBD). METHODS: Eighteen patients with CBD underwent a
      cognitive neuropsychological assessment of apraxia and resting [(18)F]
      fluorodeoxyglucose PET scanning. Two complementary measures of apraxia were
      computed for each modality of gesture production. First, a performance score
      measured error frequency during gesture execution. Second, as a more stringent
      test of the integrity of the praxis system, the correction score measured the
      patient's ability to correct his or her errors on a second attempt. For each
      measure type, a cut-off score for the presence of apraxia was defined with regard
      to healthy controls. Using each cut-off score, the regional cerebral glucose
      metabolism of patients with CBD with apraxia (i.e., performing below cut-off
      score) was compared with that of patients with CBD without apraxia. RESULTS: Mean
      performance scores were below normal values in all modalities. Anterior cingulate
      hypometabolism predominated in patients with CBD who performed below the cut-off
      performance score. At variance, mean correction scores were below normal values
      for gesture imitation only. Hypometabolism in superior parietal lobule and
      supplementary motor area characterized patients with CBD who were unable to
      correct their errors at the same rate as control subjects did. CONCLUSIONS:
      Distinct neural networks underlie distinct aspects of the upper limb apraxic
      deficits in CBD. Extending previous findings of gesture production deficits in
      CBD, the use of complementary measures of apraxic behavior discloses a
      visuoimitative upper limb apraxia in CBD, underlain by a metabolic decrease in a
      parietofrontal neural network.

PMID- 11591847
TI  - Autism in tuberous sclerosis complex is related to both cortical and subcortical
      dysfunction.
AB  - OBJECTIVE: To examine the relationship between autism and epilepsy in relation to
      structural and functional brain abnormalities in children with tuberous sclerosis
      complex (TSC). METHODS: Children with TSC and intractable epilepsy underwent MRI
      as well as PET scans with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) and alpha
      [(11)C]methyl-L-tryptophan (AMT). Based on the results of Autism Diagnostic
      Interview-Revised, Gilliam Autism Rating Scale, and overall adaptive behavioral
      composite (OABC) from Vineland Adaptive Behavior Scale, subjects were divided
      into three groups: autistic (OABC < 70; n = 9), mentally-retarded nonautistic
      (OABC < 70; n = 9), and relatively normal intelligence (OABC > or = 70; n = 8).
      RESULTS: PET studies showed that the autistic group had decreased glucose
      metabolism in the lateral temporal gyri bilaterally, increased glucose metabolism
      in the deep cerebellar nuclei bilaterally, and increased AMT uptake in the
      caudate nuclei bilaterally, compared to the mentally-retarded nonautistic group.
      In addition, a history of infantile spasms and glucose hypometabolism in the
      lateral temporal gyri were both significantly associated with communication
      disturbance. Glucose hypermetabolism in the deep cerebellar nuclei and increased
      AMT uptake in the caudate nuclei were both related to stereotypical behaviors and
      impaired social interaction, as well as communication disturbance. CONCLUSIONS:
      These results suggest that generalized epilepsy in early life and functional
      deficits in the temporal neocortices may be associated with communication delays,
      and that functional imbalance in subcortical circuits may be associated with
      stereotypical behaviors and impaired social interaction in children with TSC.

PMID- 11591848
TI  - Molecular heterogeneity of oligodendrogliomas suggests alternative pathways in
      tumor progression.
AB  - OBJECTIVE: To identify different genetic molecular profiles in oligodendrogliomas
      and to evaluate their prognostic significance. METHODS: The main genetic
      alterations reported in glial tumors were investigated in 26 oligodendrogliomas
      (10 World Health Organization grade II and 16 World Health Organization grade
      III). Correlation between identified molecular changes and pathologic grade or
      clinical course was subsequently analyzed using univariate and multivariate
      statistical analyses. RESULTS: Loss of heterozygosity (LOH) on chromosome 1p,
      19q, and 10; P16/CDKN2A homozygous deletion; EGFR (epidermal growth factor
      receptor) amplification; and TP53 and PTEN mutations were observed in 14 (54%),
      15 (58%), 9 (35%), 7 (27%), 5 (19%), 1 (4%), and 0 cases. LOH 1p and 19q were
      tightly associated (p < 0.0001). A mutual exclusion was found between LOH 1p/19q
      and EGFR amplification (p = 0.01), P16/CDKN2A deletions (p = 0.001), or LOH on
      10q (p = 0.03), suggesting the existence of distinct genetic subsets in
      oligodendrogliomas. On univariate analysis, age <50 years (p = 0.002) and LOH 1p
      (p = 0.01) were associated with a longer progression-free survival (PFS) whereas
      LOH 10q (p = 0.03) and EGFR amplification (p = 0.007) were associated with a
      worse PFS. In multivariate analyses, age <50 years (p = 0.001) and LOH 1p (p =
      0.006) remained independent predictive factors for PFS. CONCLUSION: These results
      provide evidence for two alternative molecular pathways of progression in
      oligodendrogliomas. The first one is associated with loss of 1p and 19q and the
      second one with P16/CDKN2A deletion, 10q loss, and EGFR amplification. The
      findings confirm the value of loss of 1p as predictor of longer progression-free
      survival; in addition, the study demonstrates the unfavorable impact of 10q loss
      and EGFR amplification on the prognosis.

PMID- 11591849
TI  - Immune reactivity in a mouse model of familial ALS correlates with disease
      progression.
AB  - OBJECTIVE: The cause of motor neuron death in ALS is incompletely understood.
      This study aims to define the potential involvement of nonneuronal immune
      inflammatory factors in the destruction of motor neurons in mutant superoxide
      dismutase-1 (SOD1) transgenic mice as a model of ALS. BACKGROUND: The presence of
      activated microglia, IgG and its receptor for Fc portion (FcgammaRI), and T
      lymphocytes in the spinal cord of both patients with ALS and experimental animal
      models of motor neuron disease strongly suggests that immune-inflammatory factors
      may be actively involved in the disease process. METHODS: The expression of
      immune-inflammatory factors was followed in both human mutant (G93A) SOD1
      transgenic mice and human wild-type SOD1 transgenic mice, at different ages (40,
      80, and 120 days). Fixed, frozen, free-floating sections of the lumbar spinal
      cord were stained with antibodies against CD11b, IgG, FcgammaRI, intercellular
      adhesion molecule-1 (ICAM-1), CD3, and glial fibrillary acidic protein. RESULTS:
      The earliest change observed was the upregulation of ICAM-1 in the ventral lumbar
      spinal cord of 40-day-old mutant SOD1 mice. IgG and FcgammaRI reactivities were
      detected on motor neurons as early as 40 days and on microglial cells at later
      stages. Microglial activation was first evident in the ventral horn at 80 days,
      whereas reactive astrocytes and T cells became most prominent in 120-day-old
      mutant SOD1 mice. CONCLUSION: The upregulation of proinflammatory factors during
      early presymptomatic stages as well as the expansion of immune activation as
      disease progresses in mutant SOD1 transgenic mice suggest that immune
      inflammatory mechanisms could contribute to disease progression.

PMID- 11591850
TI  - Sleep-disordered breathing and respiratory failure in acid maltase deficiency.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) and respiratory failure (RF) are
      complications of acid maltase deficiency (AMD), a rare hereditary myopathy.
      OBJECTIVE: To define the relationship between lung and respiratory muscle
      function, to establish incidence and patterns of SDB, and to determine daytime
      predictors of SDB. METHODS: Sitting and supine lung and respiratory muscle
      function tests were obtained in 27 subjects with juvenile and adult AMD (aged 39
      +/- 19 years) and compared with outcomes of polysomnography. RESULTS: Ventilatory
      restriction was present in 17/27 subjects. Inspiratory vital capacity (IVC)
      correlated (p < 0.005) with peak inspiratory muscle pressure (PIP, R = 0.61),
      respiratory muscle strain (P(0.1)/P(0.1max), R = -0.68), and gas exchange by day
      (PaO(2): R = 0.71; PaCO(2): R = -0.64) and night (SaO(2): R = 0.73; P(tc)CO(2): R
      = -0.75). Diaphragm weakness (DW) was present in 13 subjects, 10 of whom had
      hypercapnic RF (PaCO(2) 65 +/- 7 mm Hg), and was associated with longer disease
      course. SDB was found in 13 subjects, 12 with DW. It was characterized by REM
      sleep hypopneas that, as ventilatory restriction worsened, were complemented by
      hypoventilation (P(tc)CO(2) > 50 mm Hg) first in REM sleep, then in non-REM sleep
      (p < 0.005). SDB was predicted by DW (sensitivity 80%, specificity 86%) and
      nocturnal hypoventilation by IVC < 40% (sensitivity 80%, specificity 93%).
      Noninvasive ventilation, instituted for daytime respiratory failure or nocturnal
      hypoventilation, normalized daytime and nocturnal gas exchange (p < 0.005).
      CONCLUSION: Vital capacity correlates with respiratory muscle function in AMD.
      Diaphragm weakness is the major cause of SDB and RF. SDB and nocturnal
      hypoventilation are predictable from daytime function tests.

PMID- 11591851
TI  - Deteriorating parkinsonism and subdural hematomas.

PMID- 11591852
TI  - Pain increases during sympathetic arousal in patients with complex regional pain
      syndrome.
AB  - OBJECTIVE: To investigate the effect of sympathetic arousal on pain and vasomotor
      responses in healthy control subjects and patients with complex regional pain
      syndrome (CRPS), and to determine whether pain increases in patients with
      particular symptoms. METHODS: In experiments 1 and 2, capsaicin was applied to
      the forearm of 24 healthy subjects to induce thermal hyperalgesia. Vascular
      responses were monitored and subjects rated thermal hyperalgesia before and after
      being startled (experiment 1), and before, during, and after mental arithmetic,
      breath holding, forehead cooling, the Valsalva maneuver, and a cold pressor test
      in experiment 2. In a third experiment, sensitivity to heat, cold, and mechanical
      stimulation was investigated in 61 patients with CRPS. Pain ratings and vascular
      and electrodermal responses were recorded after patients were startled and during
      forehead cooling. RESULTS: In experiment 1, thermal hyperalgesia decreased in
      healthy control subjects after they were startled, and digital blood vessels
      constricted symmetrically. In experiment 2, thermal hyperalgesia decreased during
      and after other forms of sympathetic arousal. However, in experiment 3, ratings
      of clinical pain increased during forehead cooling or after being startled in
      over 70% of patients with CRPS. Pain increased most consistently during forehead
      cooling in patients with cold allodynia or punctate allodynia. Digital blood
      vessels constricted more intensely on the symptomatic than the nonsymptomatic
      side in patients with CRPS during sympathetic arousal. CONCLUSIONS: Normal
      inhibitory influences on pain during sympathetic arousal are compromised in the
      majority of patients with CRPS. The augmented vasoconstrictor response in the
      symptomatic limb during sympathetic arousal is consistent with adrenergic
      supersensitivity. An adrenergic sensitivity in nociceptive afferents might
      contribute to pain and hyperalgesia during sympathetic arousal in certain
      patients with CRPS.

PMID- 11591853
TI  - Dopaminergic neurotransmission and restless legs syndrome: a genetic association
      analysis.
AB  - In order to examine the genetic substrate of the dopamine hypothesis in restless
      legs syndrome, we analyzed eight genes coding for receptors and enzymes related
      to dopaminergic transmission, using a population of 92 patients with restless
      legs syndrome and 182 controls matched for ethnic background. No significant
      differences were found in the genotypic or allelic distributions between groups.
      Furthermore, no effect of the loci examined was observed with stratification
      using clinical parameters such as age at onset or periodic leg movements during
      sleep index.

PMID- 11591854
TI  - Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless
      legs syndrome.
AB  - Fourteen drug-naive and 11 levodopa-treated patients with idiopathic restless
      legs syndrome (RLS), and 10 controls age-matched to each RLS group separately
      were examined with polysomnography (PSG), [(123)I]-(N)-(3-iodopropen-2-yl)-2beta
      carbomethoxy-3beta-(4-chlorophenyl) tropane ((123)I-IPT) SPECT, and [(123)I]-(S)
      2-hydroxy-3-iodo-6-methoxy-[(1-ethyl-2-pyrrolidinyl)methyl] benzamide ((123)I
      IBZM) SPECT. Drug-naive and levodopa-treated patients with RLS and controls
      showed similar striatal dopamine transporter and dopamine D(2)-receptor binding,
      the latter declining with age. The authors conclude that striatal dopamine
      transporter and receptor density is normal in drug-naive and levodopa-treated
      patients with RLS.

PMID- 11591855
TI  - SCA8 repeat expansions in ataxia: a controversial association.
AB  - The observation of large SCA8 alleles in healthy control subjects and nonataxic
      patients, together with a lack of segregation of the expanded repeat with ataxia
      in several families, has raised questions about the pathogenic role of the SCA8
      expansion. The authors found allele sizes within the proposed pathogenic range in
      three patients with ataxia of unknown etiology, in two individuals from pedigrees
      with either SCA2 or Friedreich's ataxia, and in two patients with Alzheimer's
      disease. Sizing of SCA8 alleles should not be a routine diagnostic test until its
      etiologic role is clarified and the pathogenic threshold is determined.

PMID- 11591856
TI  - Long-term treatment with recombinant nerve growth factor for HIV-associated
      sensory neuropathy.
AB  - HIV-associated distal sensory polyneuropathy (DSP) is a common complication of
      AIDS. No effective treatment is available. The authors investigated the long-term
      effect (48 weeks) of the neurotrophin nerve growth factor (NGF) in an open-label
      study of 200 subjects with HIV-associated DSP. Similar to their previously
      reported double-blind study, the authors showed that NGF was safe and well
      tolerated and significantly improved pain symptoms. However, there was no
      improvement of neuropathy severity as assessed by neurologic examination,
      quantitative sensory testing, and epidermal nerve fiber density.

PMID- 11591857
TI  - Acute sensory ataxic neuropathy associated with monospecific anti-GD1b IgG
      antibody.
AB  - The authors describe two patients with acute sensory ataxic neuropathy. Both had
      a profound loss of proprioception and generalized areflexia. High titers of
      monospecific anti-GD1b IgG antibody were detected in their sera during the acute
      phase. Sensory ataxia resolved within 2 weeks after the onset. Taken together
      with the induction of experimental sensory ataxic neuropathy sensitized with GD1b
      ganglioside, GD1b may be a target molecule for autoantibody in some patients with
      acute sensory ataxic neuropathy.

PMID- 11591858
TI  - Congenital muscular dystrophy with primary partial laminin alpha2 chain
      deficiency: molecular study.
AB  - The authors report a case of congenital muscular dystrophy with mild
      nonprogressive muscle weakness, white matter hypodensity, and absence of the
      laminin alpha2 chain in muscle fibers with two antibodies, but not with four
      others. They identified mutations in LAMA2, which explain the partial laminin
      alpha2 deficiency. Analysis of this case and two others allows us to refine the
      epitopes of two of the commercial antibodies, and illustrate the importance of
      using antibodies directed against different domains of the protein.

PMID- 11591859
TI  - Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon
      cause in the UK.
AB  - Eleven of 36 families with hypokalemic periodic paralysis (hypoPP) harbored
      mutations in the skeletal muscle calcium channel gene (CACNA1S). The authors
      screened the skeletal muscle sodium channel gene (SCN4A) in the remainder. One
      family harbored a new heterozygous point mutation C2014A in exon 12 (R672S) of
      SCN4A. The authors identified the genetic defect underlying hypoPP in 33% of
      individuals tested. The authors conclude that SCN4A mutations are an uncommon
      cause of hypoPP in this UK population.

PMID- 11591861
TI  - High-grade carotid stenosis detected before general surgery: is endarterectomy
      indicated?
AB  - The risk of stroke in unselected patients and patients with a carotid bruit
      undergoing general anesthesia and surgery is very low. The incremental risk
      related to known carotid stenosis is uncertain. The authors studied 284 patients
      with ultrasound studies before general surgery, 224 of whom demonstrated carotid
      stenosis. Carotid stenosis was related to a perioperative risk of stroke of
      approximately 3.6%. Greater degrees of stenosis did not confer significantly
      higher risk. Although higher than in the unselected population, this risk does
      not appear sufficient to mandate prophylactic endarterectomy.

PMID- 11591860
TI  - Fibromyalgia is common in patients with transformed migraine.
AB  - Fibromyalgia (FM) and transformed migraine (TM) are common chronic pain
      disorders. The authors estimated the prevalence of FM in 101 patients with TM,
      and analyzed its relationship to depression, anxiety, and insomnia. FM was
      diagnosed in 35.6% of cases. Patients with FM had more insomnia, were older, and
      had headaches that were more incapacitating than patients without FM. Insomnia
      and depression predicted FM in patients with TM.

PMID- 11591862
TI  - Prognosis after percutaneous closure of patent foramen ovale for paradoxical
      embolism.
AB  - The long-term risk and risk factors for recurrent embolism after percutaneous
      closure of patent foramen ovale (PFO) were investigated in 152 consecutive
      patients with presumed paradoxical embolism. During follow-up, the actuarial
      freedom from recurrent embolism was 95.1% at 1 year, and 90.6% at 2 and 6 years.
      A residual shunt after percutaneous PFO closure was a predictor for recurrence
      (RR 5.3; 95% CI 1.3 to 21.0; p = 0.02). Randomized trials comparing medical
      treatment with percutaneous PFO closure in the prevention of recurrent embolism
      are in progress.

PMID- 11591863
TI  - Improving patient selection for coagulopathy testing in the setting of acute
      ischemic stroke.
AB  - To improve patient selection for specialized coagulation testing in the setting
      of ischemic stroke, the authors sought to identify factors associated with the
      presence of hypercoagulable states. Of 208 patients with ischemic stroke tested,
      undetermined stroke subtype was significantly associated with the presence of
      coagulopathy, but only 60% were treated with warfarin. The frequency of
      coagulopathy in selected patients with ischemic stroke (5%) is low, and
      establishing the diagnosis did not uniformly influence treatment.

PMID- 11591864
TI  - Status epilepticus due to human parvovirus B19 encephalitis in an immunocompetent
      adult.
AB  - Human parvovirus (HPV) B19 is a rare cause of encephalitis in children and
      immunocompromised adults. The authors describe a case of an otherwise healthy
      woman who developed encephalitis complicated by prolonged status epilepticus.
      Human parvovirus B19 infection was suggested by a prodromal, malar rash and
      established by the presence of specific IgM and IgG antibodies in the patient's
      serum. This is the first reported case of HPV B19 encephalitis in an
      immunocompetent adult.

PMID- 11591865
TI  - rTMS of the unaffected hemisphere transiently reduces contralesional visuospatial
      hemineglect.
AB  - To verify the role of interhemispheric influences on manifestations of neglect,
      the authors investigated the effects of a transient repetitive transcranial
      magnetic stimulation (rTMS)-induced disruption of the unaffected hemisphere on
      contralesional visuospatial neglect in two left- and five right-brain-damaged
      patients. Parietal rTMS of the unaffected hemisphere during the execution of a
      computerized task of bisected line's length judgment transiently decreased the
      magnitude of neglect as expressed in the number of errors.

PMID- 11591866
TI  - Association of a tumor necrosis factor alpha polymorphism with MS susceptibility.

PMID- 11591867
TI  - Ovarian hyperstimulation syndrome with ischemic stroke due to an intracardiac
      thrombus.

PMID- 11591868
TI  - High frequency of the H63D mutation of the hemochromatosis gene (HFE) in
      malignant gliomas.

PMID- 11591869
TI  - Migrainous aura starting several minutes after the onset of subarachnoid
      hemorrhage.

PMID- 11591870
TI  - MRI assessment of spared fibers following callosotomy: a second look.

PMID- 11591872
TI  - Aphasia breaks the news.

PMID- 11591871
TI  - Henry Cavendish: an early case of Asperger's syndrome?

PMID- 11591873
TI  - HTLV-I associated myelopathy/tropical spastic paraparesis with
      pseudohypothyroidism.

PMID- 11591874
TI  - Enhancing analogic reasoning with rTMS over the left prefrontal cortex.

PMID- 11591875
TI  - Hallucinations, REM sleep, and Parkinson's disease: a medical hypothesis.

PMID- 11591876
TI  - Samuel Adams' tremor.

PMID- 11591877
TI  - Noninvasive ventilation allows gastrostomy tube placement in patients with
      advanced ALS.

PMID- 11591879
TI  - Short-term high-fat diet alters substrate utilization during exercise but not
      glucose tolerance in highly trained athletes.
AB  - We determined the effect of a high-fat diet and carbohydrate (CHO) restoration on
      substrate oxidation and glucose tolerance in 7 competitive ultra-endurance
      athletes (peak oxygen uptake [VO(2peak)] 68 +/- 1 ml x kg(-1) x min(-1); mean +/-
      SEM). For 6 days, subjects consumed a random order of a high-fat (69% fat; FAT
      adapt) or a high-CHO (70% CHO; HCHO) diet, each followed by 1 day of a high-CHO
      diet. Treatments were separated by an 18-day wash out. Substrate oxidation was
      determined during submaximal cycling (20 min at 65% VO(2peak)) prior to and
      following the 6 day dietary interventions. Fat oxidation at baseline was not
      different between treatments (17.4 +/- 2.1 vs. 16.1 +/- 1.3 g x 20 min(-1) for
      FAT-adapt and HCHO, respectively) but increased 34% after 6 days of FAT-adapt (to
      23.3 +/- 0.9 g x 20 min(-1), p < .05) and decreased 30% after HCHO (to 11.3 +/-
      1.4 g x 20 min(-1), p < .05). Glucose tolerance, determined by the area under the
      plasma [glucose] versus time curve during an oral glucose tolerance (OGTT) test,
      was similar at baseline (545 +/- 21 vs. 520 +/- 28 mmol x L(-1) x 90 min(-1)),
      after 5-d of dietary intervention (563 +/- 26 vs. 520 +/-18 mmol x L(-1) x 90
      min(-1)) and after 1 d of high-CHO (491 +/- 28 vs. 489 +/- 22 mmol x L(-1) x 90
      min(-1) for FAT- adapt and HCHO, respectively). An index of whole-body insulin
      sensitivity ( S(I), 10000/divided by fasting [glucose] x fasting [insulin] x mean
      [glucose] during OGTT x mean [insulin] during OGTT) was similar at baseline (15
      +/- 2 vs. 17 +/- 5 arbitrary units), after 5-d of dietary intervention (15 +/- 2
      vs. 15 +/- 2) and after 24 h of CHO loading (17 +/- 3 vs. 18 +/- 2 for FAT- adapt
      and HCHO, respectively). We conclude that despite marked changes in the pattern
      of substrate oxidation during submaximal exercise, short-term adaptation to a
      high-fat diet does not alter whole-body glucose tolerance or an index of insulin
      sensitivity in highly-trained individuals.

PMID- 11591880
TI  - Resistance training affects iron status in older men and women.
AB  - OBJECTIVE: To examine the effects of resistance training on hematological and
      selected indices of iron status in 17 women aged 54-71 years and 18 men aged 56
      69 years. DESIGN: Tests and evaluations were done before and after all subjects
      participated in a resistance-training program twice weekly for 12 weeks. RESULTS:
      The resistance training was effective as evidenced by increases in skeletal
      muscle strength of 20 +/- 9% and 23 +/- 13% for the men and women, respectively.
      Hematological parameters and serum iron concentrations were within normal
      clinical ranges and were unchanged by resistance training for both the men and
      the women. Total iron binding capacity (TIBC) and transferrin saturation were
      also unaffected by resistance training in the women but were significantly
      affected in the men. The men showed a decreased TIBC (p < .0001) and an increased
      transferrin saturation (p = .050). Serum ferritin concentrations decreased
      significantly in the women (p = .041) but were unchanged in the men. Transferrin
      receptor concentrations were unaffected by resistance training in the women but
      increased significantly in the men (p = .030). CONCLUSIONS: With resistance
      training, iron status of older men and women changes in a sex specific way.

PMID- 11591881
TI  - Nutritional status of U.S. elite female heptathletes during training.
AB  - This study describes the body composition, dietary nutrient intake, dietary
      practices, and biochemical indices of iron status of elite female American
      heptathletes during training. Four-day diet records and dietary practice
      questionnaires were obtained from 19 female heptathletes (26 +/- 3 years) during
      the training season. Anthropometric measurements and fasting blood samples were
      obtained at the lowest phase of the training cycle. These athletes had a low body
      fat (13.8 +/- 2.7%) and high fat-free mass to height ratios (33.0 +/- 2.0 kg/m).
      Average nutrient intakes were > 67% of the reference intakes for all nutrients
      except vitamin E. Most dietary nutrient densities were higher than NHANES III
      nutrient densities for women 20-29 years old. More than 50% of the athletes took
      vitamin supplements and monitored their hydration status. Fifteen of the 17
      athletes reported a normal menstrual cycle. Markers of biochemical iron status
      were all within the normal range. On average, these athletes were lean with high
      levels of fat free mass, adequate nutrient intakes, and normal biochemical
      indices of iron status. However, individual data reveals considerable variability
      within this group.

PMID- 11591882
TI  - Effect of glycerol-induced hyperhydration on thermoregulation and metabolism
      during exercise in heat.
AB  - This study examined the effect of glycerol ingestion on fluid homeostasis,
      thermoregulation, and metabolism during rest and exercise. Six endurance-trained
      men ingested either 1 g glycerol in 20 ml H2O x kg(-1) body weight (bw) (GLY) or
      20 ml H2O x kg(-1) bw (CON) in a randomized double-blind fashion, 120 min prior
      to undertaking 90 min of steady state cycle exercise (SS) at 98% of lactate
      threshold in dry heat (35 degrees C, 30% RH), with ingestion of CHO-electrolyte
      beverage (6% CHO) at 15-min intervals. A 15-min cycle, where performance was
      quantified in kJ, followed (PC). Pre-exercise urine volume was lower in GLY than
      CON (1119 +/- 97 vs. 1503 +/- 146 ml x 120 min(-1); p < .05). Heart rate was
      lower (p < .05) throughout SS in GLY, while forearm blood flow was higher (17.1
      +/- 1.5 vs. 13.7 +/- 3.0 ml x 100 g tissue x min(-1); p < .05) and rectal
      temperature lower (38.7 +/- 0.1 vs. 39.1 +/- 0.1 degrees C; p < .05) in GLY late
      in SS. Despite these changes, skin and muscle temperatures and circulating
      catecholamines were not different between trials. Accordingly, no differences
      were observed in muscle glycogenolysis, lactate accumulation, adenine nucleotide,
      and phosphocreatine degradation or inosine 5'-monophosphate accumulation when
      comparing GLY with CON. Of note, the work performed during PC was 5% greater in
      GLY (252 +/- 10 vs. 240 +/- 9 kJ; p < .05). These results demonstrate that
      glycerol, when ingested with a bolus of water 2 hours prior to exercise, results
      in fluid retention, which is capable of reducing cardiovascular strain and
      enhancing thermoregulation. Furthermore, this practice increases exercise
      performance in the heat by mechanisms other than alterations in muscle
      metabolism.

PMID- 11591883
TI  - Educational strategies used in increasing fluid intake and enhancing hydration
      status in field hockey players preparing for competition in a hot and humid
      environment: a case study.
AB  - The purpose of the present study was to develop a hydration strategy for use by
      female English field hockey players at the 1998 Commonwealth Games in Malaysia.
      An additional aim was to initiate the process of acclimation. Fifteen elite
      players, mean age (+/-SEM) 24.1 +/- 1.19 years, height 1.67 +/- 0.01 m, and body
      mass 62.8 +/- 1.76 kg, took part in a 5-day training camp immediately prior to
      departure for the Games. In order to develop the hydration strategy, training
      took place under similar environmental conditions to those to be experienced in
      Malaysia (i.e., 32 degrees C, 80% humidity). Acclimation training consisted of 30
      50 min of either continuous, low intensity cycling or high intensity intermittent
      cycling, which more closely replicated the pattern of activity in field hockey.
      Body mass measures taken each morning, and pre and post training, together with
      urine color measures, were used to assess hydration status. Pre-loading with up
      to 1 L of a 3% carbohydrate-electrolyte solution or water immediately prior to
      acclimation training, as well as regular drinks throughout, ensured that players
      avoided significant dehydration, with percent body mass changes ranging from 
      0.34% to +4.24% post training. Furthermore, the protocol used was sufficient to
      initiate the process of acclimation as demonstrated by a significant reduction in
      exercising heart rate and core temperature at all time points by days 4 and 5. In
      conclusion, although labor intensive and time consuming, the camp was successful
      in developing a hydration strategy that players were able to utilize once at the
      Games.

PMID- 11591884
TI  - The effect of whey protein supplementation with and without creatine monohydrate
      combined with resistance training on lean tissue mass and muscle strength.
AB  - Our purpose was to assess muscular adaptations during 6 weeks of resistance
      training in 36 males randomly assigned to supplementation with whey protein (W;
      1.2 g/kg/day), whey protein and creatine monohydrate (WC; 0.1 g/kg/day), or
      placebo (P; 1.2 g/kg/day maltodextrin). Measures included lean tissue mass by
      dual energy x-ray absorptiometry, bench press and squat strength (1-repetition
      maximum), and knee extension/flexion peak torque. Lean tissue mass increased to a
      greater extent with training in WC compared to the other groups, and in the W
      compared to the P group (p < .05). Bench press strength increased to a greater
      extent for WC compared to W and P (p < .05). Knee extension peak torque increased
      with training for WC and W (p < .05), but not for P. All other measures increased
      to a similar extent across groups. Continued training without supplementation for
      an additional 6 weeks resulted in maintenance of strength and lean tissue mass in
      all groups. Males that supplemented with whey protein while resistance training
      demonstrated greater improvement in knee extension peak torque and lean tissue
      mass than males engaged in training alone. Males that supplemented with a
      combination of whey protein and creatine had greater increases in lean tissue
      mass and bench press than those who supplemented with only whey protein or
      placebo. However, not all strength measures were improved with supplementation,
      since subjects who supplemented with creatine and/or whey protein had similar
      increases in squat strength and knee flexion peak torque compared to subjects who
      received placebo.

PMID- 11591885
TI  - Inadvertent doping through supplement use by athletes: assessment and management
      of the risk in Australia.
AB  - Many athletes report using a wide range of special sports foods and supplements.
      In the present study of 77 elite Australian swimmers, 99% of those surveyed
      reported the use of these special preparations, with 94% of swimmers reporting
      the use of non-food supplements. The most popular dietary supplements were
      vitamin or mineral supplements (used by 94% of the group), herbal preparations
      (61%), and creatine (31%). Eighty-seven percent of swimmers reported using a
      sports drink or other energy-providing sports food. In total, 207 different
      products were reported in this survey. Sports supplements, particularly
      supplements presented as pills or other non-food form, are poorly regulated in
      most countries, with little assurance of quality control. The risk of an
      inadvertent "positive doping test" through the use of sports supplements or
      sports foods is a small but real problem facing athletes who compete in events
      governed by anti-doping rules. The elite swimmers in this survey reported that
      information about the "doping safety" of supplements was important and should be
      funded by supplement manufacturers. Although it is challenging to provide such
      information, we suggest a model to provide an accredited testing program suitable
      for the Australian situation, with targeted athlete education about the "sports
      safety" of sports supplements and foods.

PMID- 11591886
TI  - MRP8, a new member of ABC transporter superfamily, identified by EST database
      mining and gene prediction program, is highly expressed in breast cancer.
AB  - BACKGROUND: With the completion of the human draft genome sequence, efforts are
      now devoted to identifying new genes. We have developed a computer-based strategy
      that utilizes the EST database to identify new genes that could be targets for
      the immunotherapy of cancer or could be involved in the multistep process of
      cancer. MATERIALS AND METHODS: Utilizing our computer-based screening strategy,
      we identified a cluster of expressed sequence tags (ESTs) that are highly
      expressed in breast cancer. Northern blot and reverse transcriptase polymerase
      chain reaction (RT-PCR) analyses demonstrated the tissue specificity of the
      computer-generated cluster and comparison with the human genome sequence assisted
      in isolating a full-length cDNA clone. RESULTS: We identified a new gene that is
      highly expressed in breast cancer. This gene is expressed at moderate levels in
      normal breast and testis and at very low levels in liver, brain, and placenta.
      The gene has two major transcripts of 4.5 kb and 4.1 kb. The 4.5-kb transcript is
      very abundant in breast cancer, and has an open reading frame of 1382 amino
      acids. The predicted protein sequence of the 4.5-kb transcript reveals that it
      has high homology with MRP5, a member of multidrug resistant-associated protein
      family (MRP). There are seven reported members in the MRP family; we designate
      this gene as MRP8 (ABCC11). The 4.5-kb MRP8 transcript consists of 31 exons and
      is located in a genomic region of over 80.4 kb on chromosome 16q12.1. The smaller
      4.1-kb transcript of MRP8 is found in testis and may initiate within intron 6 of
      the gene. CONCLUSION: The selective expression of MRP8 (ABCC11), a new member of
      ATP-binding cassette transporter superfamily could be a molecular target for the
      treatment of breast cancer.

PMID- 11591887
TI  - Inhibition of amyloidosis using low-molecular-weight heparins.
AB  - BACKGROUND: Amyloid diseases are characterized by the tissue deposition of
      extracellular proteinaceous material, which results in organ dysfunction and
      death. Colocalization of heparan sulfate (HS) proteoglycans to amyloid deposits
      suggests that they may be an early event in amyloid formation and play an
      important role in fibril formation. Structural analysis has demonstrated that HS
      interacts with amyloidogenic proteins resulting in structural changes that allow
      for an increase in beta-sheet content, possibly enhancing fibrillogenesis. Recent
      studies have shown that small-molecule anionic sulfonates or sulfates can arrest
      inflammation-associated (AA) amyloid induction. MATERIALS AND METHODS: In the
      present study, we examine the effect of low-molecular-weight heparins (LMWHs) on
      the development of amyloid in the mouse model of AA amyloid. In addition, in
      vitro fibril formation assays were performed to determine the effect of LMWHs on
      fibrillogenesis. RESULTS: Injection of mice with clinically relevant doses of
      LMWHs (enoxaparin and dalteparin) demonstrated a reduction in AA amyloid
      deposition. These compounds were capable of arresting the progression of AA
      amyloid and eventually resulting in regression of the amyloid deposits. In vitro
      analysis indicated that LMWHs prevented AA and Abeta peptide fibril formation by
      impeding the structural changes necessary for fibril formation. CONCLUSIONS: Our
      findings suggest that the LMWHs may provide beneficial effects against the
      development of amyloidoses, including Alzheimer's disease.

PMID- 11591889
TI  - Influence of age and gender on the clinical expression of acute intermittent
      porphyria based on molecular study of porphobilinogen deaminase gene among Swiss
      patients.
AB  - BACKGROUND: Acute intermittent porphyria (AIP) is an inherited disorder in the
      heme biosynthetic pathway caused by a partial deficiency of porphobilinogen (PBG)
      deaminase. Clinically, AIP is characterized as acute neurovisceral attacks that
      are often precipitated by exogenous factors such as drugs, hormones, and alcohol.
      An early detection of mutation carriers is essential for prevention of acute
      attacks by avoiding precipitating factors. This study was aimed at analyzing
      genetic defects causing AIP among Swiss families to further investigate aspects
      concerning the clinical expression of the disease. MATERIALS AND METHODS: The
      PBGD gene of index patients from 21 Swiss AIP families was systematically
      analyzed by denaturing gradient gel electrophoresis of polymerase chain reaction
      (PCR) amplified DNA fragments and direct sequencing. RESULTS: Five new mutations
      insA503, del L170, T190I, P241S, and R321H, as well as three known mutations
      (R26H, R173Q and W283X) were detected. Twelve of the 21 index patients (57%)
      carried the prevalent mutation W283X previously found among the Swiss AIP
      population. Family-specific mutations were then screened among relatives of the
      index patients. Among the 107 studied individuals, 58 carried a PBGD gene
      mutation--30 were overt AIP patients and 28 were asymptomatic carriers. The
      apparent rate of overt disease in the study cohort was 52%, which is
      significantly higher than the previously reported penetrance of 10-20%. To
      further examine the clinical expression of AIP, the cumulative life-time risk was
      calculated among 58 mutation-positive individuals after stratifying for age. The
      result shows a linear increase of the percentage of the symptomatic patients with
      age, reaching up to 75% among carriers aged over 60. Moreover, statistical
      analysis of the gender distribution among patients and asymptomatic carriers
      indicated that the disease was more frequently expressed among females than males
      (Fisher's exact test two sided, p= (0.001). CONCLUSIONS: This comprehensive
      search for genetic defects in the PBGD gene confirmed the existence of a
      prevalent mutation W283X among Swiss AIP patients, as well as a number of family
      private mutations. Genetic analysis laid a groundwork for further studies such as
      the effects of gender and age on the clinical expression of AIP.

PMID- 11591888
TI  - Control of the proinflammatory state in cystic fibrosis lung epithelial cells by
      genes from the TNF-alphaR/NFkappaB pathway.
AB  - BACKGROUND: Cystic fibrosis (CF) is the most common, lethal autosomal recessive
      disease affecting children in the United States and Europe. Extensive work is
      being performed to develop both gene and drug therapies. The principal mutation
      causing CF is in the CFTR gene ([Delta F508]CFTR). This mutation causes the
      mutant protein to traffic poorly to the plasma membrane, and degrades CFTR
      chloride channel activity. CPX, a candidate drug for CF, binds to mutant CFTR and
      corrects the trafficking deficit. CPX also activates mutant CFTR chloride channel
      activity. CF airways are phenotypically inundated by inflammatory signals,
      primarily contributed by sustained secretion of the proinflammatory cytokine
      interleukin 8 (IL-8) from mutant CFTR airway epithelial cells. IL-8 production is
      controlled by genes from the TNF-alphaR/NFkappaB pathway, and it is possible that
      the CF phenotype is due to dysfunction of genes from this pathway. In addition,
      because drug therapy with CPX and gene therapy with CFTR have the same common
      endpoint of raising the levels of CFTR, we have hypothesized that either approach
      should have a common genomic endpoint. MATERIALS AND METHODS: To test this
      hypothesis, we studied IL-8 secretion and global gene expression in IB-3 CF lung
      epithelial cells. The cells were treated by either gene therapy with wild-type
      CFTR, or by pharmacotherapy with the CFTR-surrogate drug CPX. CF cells, treated
      with either CFTR or CPX, were also exposed to Pseudomonas aeruginosa, a common
      chronic pathogen in CF patients. cDNA microarrays were used to assess global gene
      expression under the different conditions. A novel bioinformatic algorithm
      (GENESAVER) was developed to identify genes whose expression paralleled secretion
      of IL-8. RESULTS: We report here that IB3 CF cells secrete massive levels of IL
      8. However, both gene therapy with CFTR and drug therapy with CPX substantially
      suppress IL-8 secretion. Nonetheless, both gene and drug therapy allow the CF
      cells to respond with physiologic secretion of IL-8 when the cells are exposed to
      P. aeruginosa. Thus, neither CFTR nor CPX acts as a nonspecific suppressor of IL
      8 secretion from CF cells. Consistently, pharmacogenomic analysis indicates that
      CF cells treated with CPX greatly resemble CF cells treated with CFTR by gene
      therapy. Additionally, the same result obtains in the presence of P. aeruginosa.
      Classical hierarchical cluster analysis, based on similarity of global gene
      expression, also supports this conclusion. The GENESAVER algorithm, using the IL
      8 secretion level as a physiologic variable, identifies a subset of genes from
      the TNF-alphaR/NFkappaB pathway that is expressed in phase with IL-8 secretion
      from CF epithelial cells. Certain other genes, previously known to be positively
      associated with CF, also fall into this category. Identified genes known to code
      for known inhibitors are expressed inversely, out of phase with IL-8 secretion.
      CONCLUSIONS: Wild-type CFTR and CPX both suppress proinflammatory IL-8 secretion
      from CF epithelial cells. The mechanism, as defined by pharmacogenomic analysis,
      involves identified genes from the TNF-alphaR/NFkappaB pathway. The close
      relationship between IL-8 secretion and genes from the TNF-alphaR/NFkappaB
      pathway suggests that molecular or pharmaceutical targeting of these novel genes
      may have strategic use in the development of new therapies for CF. From the
      perspective of global gene expression, both gene and drug therapy have similar
      genomic consequences. This is the first example showing equivalence of gene and
      drug therapy in CF, and suggests that a gene therapy-defined endpoint may prove
      to be a powerful paradigm for CF drug discovery. Finally, because the GENESAVER
      algorithm is capable of isolating disease-relevant genes in a hypothesis-driven
      manner without recourse to any a priori knowledge about the system, this new
      algorithm may also prove useful in applications to other genetic diseases.

PMID- 11591890
TI  - Advanced glycation endproducts: activators of cardiac remodeling in primary
      fibroblasts from adult rat hearts.
AB  - BACKGROUND: Cardiovascular diseases are the leading cause of death in the Western
      world, especially in the elderly. Myocardial fibrosis induced by activated
      cardiac fibroblasts is thought to play a key role in the pathogenesis of
      cardiovascular disease. Accumulation of advanced glycation endproducts (AGEs),
      products of nonenzymatic glycation of proteins, correlate with the stiffness of
      the heart and large vessels. To elucidate a potential role of AGEs as a trigger
      of fibrosis, the effects of AGEs on primary fibroblasts from hearts of adult rats
      were investigated. MATERIAL AND METHODS: The activation of intracellular
      signaling pathways was shown by Western blotting. In addition, the expression of
      genes of the extracellular matrix proteins, metalloproteases (MMPs), their
      inhibitors, and TGF-beta were analyzed by semiquantitative PCR. Activation of
      MMPs were controlled by Zymography. RESULTS: It was shown that treatment of
      cardiac fibroblasts with AGEs leads to an activation of different signaling
      molecules, such as the p38MAP-kinase, the extracellular regulated kinases (ERKs),
      the jun kinase (JNK), as well as transcription factors like ATF-2 and NF-kappaB.
      In addition, the expression and activation of MMP-2, MMP-9, and MMP-13 were
      induced, which may be responsible for tissue remodeling followed by fibrosis.
      CONCLUSION: Due to their effects on the expression and activation of
      metalloproteases, AGEs should be regarded as a potential therapeutic target for
      the prevention of pathologic remodeling.

PMID- 11591891
TI  - Differentiation of myeloid cell lines correlates with a selective expression of
      RIZ protein.
AB  - BACKGROUND: The retinoblastoma-interacting zinc-finger gene RIZ is expressed in
      two forms (RIZ1 and RIZ2) that differ for the presence near the N-terminus of
      RIZ1 of a conserved domain, defined PR (PRDI-BF1-RIZ homology), homologous to a
      similar domain present in other proteins recognized as tumor suppressor gene
      products. The RIZ1 form is usually absent or expressed at low levels in tumor
      cells, whereas RIZ2 is frequently expressed. We investigated a possible
      involvement of RIZ1 in differentiation control using a myeloid cell maturation
      model that is easily modulated by retinoids and other agents. MATERIALS AND
      METHODS: HL60 or NB4 cell lines or patients' leukemic promyelocytes were treated
      with all- trans -retinoic acid or other agents to induce differentiation. RIZ
      gene expression was determined with reverse transcriptase polymerase chain
      reaction (RT-PCR) and RNase protection assay. Immunocytochemistry was performed
      to assess variation of the intracellular distribution of RIZ protein on all-
      trans-retinoic acid treatment. Forced expression of RIZ1 protein was obtained
      with a recombinant adenovirus containing RIZ1 cDNA. RESULTS: Treatment with
      retinoic acid induced a selective expression of RIZ1 in HL60 cell line. Retinoic
      acid effect was maximal at 7 days and correlated to the granulocytic
      differentiation of cells. A similar effect was obtained in retinoic acid
      sensitive NB4 cell line or in patients' leukemic promyelocytes, but not in the
      retinoic acid-resistant cell line NB4.007/6 or in the U937 cell line. Selective
      expression of RIZ1 was also induced by 12-O-tetradecanoyl-phorbol-13-acetate in
      the U937 and HL60 cell lines and by 1,25-dihydroxyvitamin D(3) only in HL60
      cells. In HL60 cells, RIZ1 was also induced by activation of a retinoid alpha
      receptor-independent maturation pathway based on retinoid X receptor agonist and
      protein kinase A synergism. In addition, retinoic acid produced a redistribution
      of the antigen within the nucleus in these cells. Forced expression of RIZ1
      protein induced growth arrest and death of HL60 cells. CONCLUSIONS: The
      correlation between the selective expression of RIZ1 induced by retinoic acid, 12
      O-tetradecanoyl-phorbol-13-acetate, or 1,25-dihydroxyvitamin D(3) and
      differentiation suggested that RIZ protein was involved in myeloid cell
      differentiation induced by these agents.

PMID- 11591893
TI  - Design and in vitro characterization of a single regulatory module for efficient
      control of gene expression in both plasmid DNA and a self-inactivating lentiviral
      vector.
AB  - BACKGROUND: Regulation of transgene expression in target cells represents a
      critical and challenging aspect of gene therapy. Recently, a two-plasmid
      tetracycline-inducible system was developed in which the tetracycline repressor
      (tetR) alone, rather than the tetR-VP16 fusion derivative, was shown to function
      as a potent trans-modulator of a second plasmid that contains two tandem repeats
      of the tetracycline operator (tetO) inserted between the TATA box and the
      transcription start site of the hCMV major immediate-early promoter. A
      technological advance in this area would be the development of a single
      autoregulatory cassette that incorporates both of these components into nonviral
      and viral gene transfer vectors. For the latter, an inducible lentiviral vector
      that is capable of temporal and quantitative control of gene expression in either
      dividing or nondividing cells is highly desirable. MATERIALS AND METHODS: A one
      piece inducible (1Pi) autoregulatory cassette was constructed to provide IRES
      mediated translation of the tetR as well as tight control over the tetO unit
      preventing transcription initiation of the first cistron in the absence of the
      tetracycline. To increase efficiency of tetR-mediated repression, a nuclear
      localization signal was incorporated at the 3' end of the tetR gene. Regulation
      of gene expression at the transcriptional and protein level was analyzed in
      transient transfection experiments using plasmid DNA. Construction of a self
      inactivating lentiviral vector containing this 1Pi cassette allowed the study of
      its long-term effectiveness in primary human cells. RESULTS: The 1Pi
      autoregulatory cassette when incorporated into plasmid DNA allows efficient
      control of the secretable hEGF as well as eGFP expression in a variety of cell
      types. Transient transfection studies demonstrated that the time course of
      repression is different for the 1Pi and two-plasmid system (2Pi). In the 2Pi
      system, greater repression is seen with the first 24-48 hr; however, by 72 hr,
      similar levels of repression with the 1Pi and 2Pi systems are obtained. This
      regulation is reached three times faster when the tetR is modified with a nuclear
      localization signal to direct nascent proteins into the nuclear compartment. In
      addition, stable transduction of human umbilical vein endothelial cells (HUVEC)
      with a self-inactivating lentiviral vector incorporating this single regulator
      cassette provided tetracycline-inducible control of gene expression that is not
      diminished over time and is completely reversible upon removal of tetracycline.
      CONCLUSIONS: These results suggest a model in which the 1Pi autoregulatory system
      reaches a steady state over time, the minimal amount of tetR produced by the
      basal activity of the CMV promoter and accumulated is adequate to replace the
      tetR that is lost over time. These studies also show that the inducible self
      inactivating lentiviral vector can temporally and reversibly regulate transgene
      expression in HUVECs. The use of this transcriptional control unit in both
      nonviral and viral vector delivery systems will constitute an attractive
      technological advance for many gene therapy applications where temporal and
      quantitative control of gene expression is desired. The strengths and limitations
      of the 1Pi system are discussed.

PMID- 11591892
TI  - Combination vascular delivery of herpes simplex oncolytic viruses and amplicon
      mediated cytokine gene transfer is effective therapy for experimental liver
      cancer.
AB  - BACKGROUND: Herpes simplex type I (HSV)-based vectors have been used
      experimentally for suicide gene therapy, immunomodulatory gene delivery, and
      direct oncolytic therapy. The current study utilizes the novel concept of
      regional delivery of an oncolytic virus in combination with or serving as the
      helper virus for packaging herpes-based amplicon vectors carrying a cytokine
      transgene, with the goal of identifying if this combination is more efficacious
      than either modality alone. MATERIALS AND METHODS: A replication competent
      oncolytic HSV (G207) and a replication incompetent HSV amplicon carrying the gene
      for the immunomodulatory cytokine IL-2 (HSV-IL2) were tested in murine syngeneic
      colorectal carcinoma and in rat hepatocellular carcinoma models. Liver tumors
      were treated with vascular delivery of (1) phosphate-buffered saline (PBS), (2)
      G207, (3) HSV-IL2, (4) G207 and HSV-IL2 mixed in combination (mG207/HSV- IL2),
      and (5) G207 as the helper virus for packaging the construct HSV-IL2 (pG207/HSV
      IL2). RESULTS: Tumor burden was significantly reduced in all treatment groups in
      both rats and mice treated with high-dose G207, HSV-IL2, or both (p < 0.02). When
      a low dose of virus was used in mice, anti-tumor efficacy was improved by use of
      G207 and HSV-IL2 in combination or with HSV-IL2 packaged by G207 (p < 0.001).
      This improvement was abolished when CD4(+) and CD8(+) lymphocytes were depleted,
      implying that the enhanced anti-tumor response to low-dose combined therapy is
      immune mediated. CONCLUSIONS: Vascular regional delivery of oncolytic and
      amplicon HSV vectors can be used to induce improved anti-tumor efficacy by
      combining oncolytic and immunostimulatory strategies.

PMID- 11591894
TI  - Effect of passive smoking on theophylline clearance in children.
AB  - The author investigated the effects of passive tobacco smoking on the metabolism
      of theophylline in a pediatric population. In a retrospective analysis of 201
      children admitted to a pediatric unit for asthma, 31 were identified with an
      acute exacerbation of asthma of noninfectious origin in which environmental
      exposure to tobacco smoke could be established. The parents were known smokers
      with a minimum 1-pack-per-day habit. An age-and gender-matched control population
      of children was then identified who had an acute exacerbation of asthma without
      any environmental exposure to tobacco smoke. In addition, the patients in both
      groups received the same dose of intravenous aminophylline for a minimum of 48
      hours to ensure steady-state conditions. Total body clearance of theophylline was
      significantly elevated in the children exposed to environmental tobacco smoke
      (1.36 +/- 0.09 vs. 0.90 +/- 0.04 mL/min per kg, p < 0.0001). Steady-state serum
      levels were significantly lower in the passive smoking group (55.3 +/- 2.8 vs.
      73.2 +/- 3.3 p < 0.00001) for those receiving nearly identical intravenous doses.
      The length of hospital stay was longer in the group exposed to passive smoke (4.4
      +/- 2.6 vs. 2.9 +/- 1.3 days, p < 0.05). The clearance of theophylline is greater
      in asthmatic children exposed to passive tobacco smoke than in asthmatic children
      not exposed to passive tobacco smoke. These findings suggest that passive smoking
      may increase the clearance of other drugs metabolized in a manner similar to
      theophylline.

PMID- 11591896
TI  - Effect of cyclosporine on mycophenolic acid area under the concentration-time
      curve in pediatric kidney transplant recipients.
AB  - Mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF),
      shows substantial interindividual and intraindividual variability. It was
      recently shown that in vitro calcineurin inhibitors alter the bioavailability of
      MPA by dose-dependent inhibition of MPA glucuronidation. The authors
      retrospectively analyzed full 10-point profiles for both MPA and cyclosporine
      (CyA) in 23 pediatric patients receiving MMF and cyclosporine microemulsion
      (Neoral; Novartis Pharmaceuticals Canada; Dorval, Quebec, Canada). Mycophenolic
      acid was measured using a commercially available EMIT (Novartis Pharmaceuticals,
      Canada) assay. As the majority of patients were treated with low doses of
      cyclosporine after adding MMF, the area under the concentration-time curve (AUC)
      for cyclosporine showed a wide scatter ranging from 296 to 6400 ng x h/mL. The
      mean cyclosporine dose was 100 +/- 76 mg/m2 per day (range: 28 to 331). There was
      no correlation between MPA AUC and MPA dose, and there was substantial
      interindividual variation. However, there was a significant negative correlation
      between dose-normalized MPA AUC and cyclosporine AUC ( r2 = 0.23, p < 0.0220).
      When dividing the MPA profiles into two groups (11 and 12 patients) with a CyA
      AUC less than or greater than 1600 ng x h/mL, there was a significantly higher 8
      hour concentration in the patients with the lower CyA AUC, secondary to a higher
      second peak. The data demonstrate that the cyclosporine AUC is a determining
      factor for the MPA AUC and that MPA dose should be reduced when cyclosporine dose
      is reduced to achieve the same MPA AUC. The significantly higher peak in the
      group with a lower CyA profile supports the concept of a dose-dependent
      cyclosporine-induced inhibition of MPA glucuronidation.

PMID- 11591895
TI  - Once-daily versus multiple-daily gentamicin in infants and children.
AB  - In this prospective randomized trial, the efficacy and safety of once-daily
      administration of gentamicin were compared with multiple-daily administration in
      infants and children. In addition, pharmacokinetic variables were calculated.
      Gentamicin therapy was started at a dose of 5 mg/kg per day under individual dose
      or dosage interval adjustments to achieve target levels. Fifty-two infants and
      children aged 1 month (postterm) to 16 years were enrolled. The duration of fever
      from the start of therapy, the percentage decline of C-reactive protein (CRP) on
      day 3 of treatment, and the clinical outcome were used as efficacy parameters.
      Nephrotoxicity was evaluated using creatinine serum levels. Basic characteristics
      in both groups were comparable. A good clinical response was observed in both
      groups. Fever may have resolved faster with multiple-daily administration, but
      this was not statistically significant. The percentage of decline of CRP was also
      comparable in both groups. Nephrotoxicity occurred in six patients, three per
      group. Many patients were too ill or too young to perform hearing tests, but no
      clinical signs of ototoxicity were observed. Mean doses of 6.8 mg/kg per day
      (multiple-daily administration) and 7.3 mg/kg per day (once-daily administration)
      were necessary to meet the target gentamicin levels. Triple-daily doses had to be
      reduced to a twice-daily regimen in 17 of 26 children. Dose and dosage interval
      adaptations can be performed by Bayesian forecasting using a one-compartment
      model with one set of K(e) and V(d) parameters. The authors consider both
      regimens equally effective, with a comparable incidence of nephrotoxicity. A
      starting dose of 6.5 mg/kg once daily is advised.

PMID- 11591897
TI  - In vivo higher glucuronidation of mycophenolic acid in male than in female
      recipients of a cadaveric kidney allograft and under immunosuppressive therapy
      with mycophenolate mofetil.
AB  - Mycophenolate mofetil (MMF), an immunosuppressant drug used in organ
      transplantation to prevent rejection, is being used increasingly in association
      with cyclosporine and tacrolimus. Mycophenolic acid (MPA) is primarily
      metabolized in the liver to its 7-O-glucuronide (MPAG) derivative. The
      concentrations of MPAG in serum are many times the concentrations of MPA.
      Although MPAG has not shown immunosuppressant activity, it was postulated that it
      could displace MPA from its binding sites on albumin and hence increase the
      biologic effects of MPA. This effect could be important for patients with acute
      renal failure; under this condition, MPAG was shown to accumulate. The goal of
      this study was to document the MPAG/MPA concentration ratio in 100 renal
      transplant patients under a mixed immunosuppressive therapy. Further, the study
      addressed the question of whether MPAG can displace MPA in vivo from bound
      albumin in a representative renal transplant patient population under
      immunosuppressive therapy. Levels of MPAG and MPA were measured by high
      performance liquid chromatography. The distribution of the ratios was not
      parametric as it tailed toward elevated values. After a square root
      transformation of the data, parametric analysis was possible. The average
      MPAG/MPA ratio was 15.0 +/- 2.2 for men versus 7.7 +/- 0.9 for women. Men treated
      with MMF and tacrolimus showed a lower ratio than patients treated with MMF and
      cyclosporine, confirming that tacrolimus inhibits glucuronidation of MPA.
      Further, it was determined that at physiologic concentrations, MPAG does not
      increase the amount of free MPA. Because MPAG can favor the elimination of MPA,
      it can be concluded that gender differences and cotreatment with tacrolimus must
      be taken into consideration when MMF is being administered.

PMID- 11591898
TI  - Monitoring of busulfan area under the curve: estimation by a single measurement.
AB  - Because the busulfan area under the concentration-time curve (AUC) has been
      correlated with the outcome of bone marrow transplantation (BMT) and the
      occurrence of veno-occlusive disease after BMT, a rapid determination of AUC is
      needed to ensure its suitable dosage. The present work describes a method based
      on combining aliquots from the 10 blood samples collected for an AUC busulfan
      determination and performing a single determination of the resulting mixture. In
      42 patients undergoing a preparative regimen for bone marrow transplantation this
      combined sample AUC was compared with the regular determined AUC obtained from 10
      consecutive samples drawn at various time intervals after dosing. It is apparent
      that the AUCs calculated by pharmacokinetic analysis using a noncompartmental
      model package and those obtained by analyzing the sample mixture are very similar
      ( r = 0.961). The proposed method allows rapid adjustment of the busulfan dose,
      reducing the number of uncorrected dosages during therapy.

PMID- 11591899
TI  - Plasma concentration of topiramate correlates with cerebrospinal fluid
      concentration.
AB  - The authors examined the ratio between the plasma and the cerebrospinal fluid
      (CSF) concentration of topiramate in 14 adults with epilepsy. Simultaneous trough
      samples of venous blood and CSF were collected and analyzed as total and unbound
      concentrations. Concomitant levels were also analyzed of lamotrigine (n = 5) and
      the relevant oxcarbazepine metabolite, 10-hydroxycarbazepine (n = 3). There was a
      close correlation between the plasma and the CSF concentration for both the total
      and unbound concentration of topiramate. The median CSF/plasma ratio of total
      topiramate was 0.85. The free topiramate concentration in plasma was not
      different from the free topiramate concentration in CSF. The CSF/plasma ratios
      showed little variation and were independent of the plasma level for both the
      total and the unbound levels. The unbound fraction of topiramate was 84% in
      plasma and 97% in CSF. The CSF concentrations of lamotrigine and 10
      hydroxycarbazepine were 50% and 61% of the plasma concentrations, respectively.
      For topiramate, there is a close correlation between the plasma concentration and
      the CSF concentration. There does not seem to be a saturable carrier mechanism
      restricting topiramate transport across the blood-brain barrier. The
      concentration of topiramate in CSF is equal to the unbound proportion of
      topiramate in plasma, implying that the delivery of topiramate to the brain
      occurs via transfer from the unbound plasma pool. Plasma is thus a relevant
      matrix for therapeutic drug monitoring of topiramate.

PMID- 11591900
TI  - Determination of thiopurine methyltransferase activity in human erythrocytes by
      high-performance liquid chromatography: comparison with the radiochemical method.
AB  - The current article describes a new assay to measure thiopurine methyltransferase
      (TPMT) activity from red blood cells. This method is based on the measurement of
      the reaction product 6-methylmercaptopurine (6-MMP) by high-performance liquid
      chromatography (HPLC). 6-MMP is extracted by ethyl acetate with recoveries of
      85%, 80%, 80%, and 92% for 50, 250, 500, and 1,000 ng/100 microL packed red blood
      cells, respectively. 6-MMP was identified and measured by a Zorbax CN column
      installed in an HPLC system. The chromatograms were resolved using a mobile phase
      consisting of 40 mmol/L sodium phosphate buffer (pH 3) and methanol in a gradient
      from 1% to 20% of methanol. Under these conditions 6-MMP is well resolved from
      substrates (6-mercaptopurine and S-adenosyl-L-methionine) and endogenous peaks.
      When the TPMT activity from 20 patients was measured by the HPLC-linked assay and
      the classic radiochemical method, a linear correlation was obtained between both
      procedures ( y = 0.99x + 0.33; x-axis, radiochemical assay; y-axis, HPLC-linked
      assay; r = 0.98). In conclusion, the current report describes a new, reliable,
      safe, and nonradioactive method to measure TPMT activity that is shorter and
      simpler than the previously described ones.

PMID- 11591901
TI  - Glutathione stability in whole blood: effects of various deproteinizing acids.
AB  - High-performance liquid chromatography separation of reduced and oxidized
      glutathione (GSH and GSSG) in biologic samples using electrochemical detection
      offers the convenience of both simultaneous quantitation and simple sample
      preparation. Rapid acidification is required to prevent GSH autooxidation, GSH
      and GSSG degradation, and precipitate proteins that interfere with analysis.
      Currently, little consistency exists in the literature regarding acid selection
      or the feasibility of sample storage before analysis. The purpose of this work
      was to examine the effects of perchloric (PCA), trichloroacetic (TCA),
      metaphosphoric (MPA), and 5-sulfosalicylic (SSA) acids on the short-term
      stability of GSH and GSSG measurements in whole blood. Samples were collected
      from adult volunteers and treated with multiple concentrations of each acid. The
      samples were analyzed immediately and aliquots were stored at -80 degrees C for
      up to 28 days. The suitability of each acid was assessed by percentage change of
      GSH and GSSG from baseline, efficiency of protein removal, and alteration of
      chromatogram characteristics. In general, increasing the acid concentration
      improved sample stability. Nevertheless, SSA did not achieve acceptable sample
      stability at any concentration tested. MPA was found to leave substantial amounts
      of protein in the samples, and TCA may interfere with the peaks of interest.
      Based on these results, a final concentration of 15% PCA is suggested for
      analysis of glutathione in whole blood. Although immediate sample preparation is
      preferred, 15% PCA can maintain sample integrity for 4 weeks after storage at -80
      degrees C.

PMID- 11591902
TI  - Stability of sufentanil in human plasma samples.
AB  - The stability of sufentanil in human plasma kept under various storage conditions
      was investigated. Extraction was performed using solid phase extraction with new
      mixed-mode cation exchange Oasis MCX columns; quantification was carried out
      using gas chromatography equipped with a mass spectrometry detector. When plasma
      was left at 4 degrees C in nonsilanized tubes, concentrations of sufentanil
      decreased significantly during the first hour. In plasma samples kept at -25
      degrees C for 8 hours in nonsilanized glass tubes, a significant decrease of
      sufentanil concentrations was found, with an average loss of 10.1% of the initial
      concentration. A significant decrease occurred when plasma was kept in silanized
      glass tubes for 12 hours at -25 degrees C. The current study emphasizes the
      importance of sampling and storage conditions for an accurate determination of
      sufentanil concentration in plasma.

PMID- 11591903
TI  - Methadone blood concentrations are decreased by the administration of abacavir
      plus amprenavir.
AB  - Abacavir and amprenavir, a nucleoside reverse transcription inhibitor and a
      protease inhibitor, respectively, are new drugs used for the treatment of HIV.
      Methadone blood concentrations were measured in five addict patients receiving
      methadone maintenance therapy before and after introduction of abacavir plus
      amprenavir. The administration of these two drugs for a median period of 14 days
      resulted in a significant reduction (P = 0.043) of methadone concentration, with
      a median decrease to 35% of the original concentration (range 28-87%). Two
      patients reported on several occasions nausea in the morning before the intake of
      the daily methadone dose, which is compatible with withdrawal reaction to
      opioids. Because amprenavir is a cytochrome P4503A4 substrate and is involved in
      the metabolism of methadone, reduction of methadone concentrations could be
      explained by an induction of cytochrome P4503A4.

PMID- 11591904
TI  - Oral contraceptives increase the plasma concentrations of chlorpromazine.
AB  - A 21-year-old female inpatient who was enrolled in a population pharmacokinetic
      study of chlorpromazine was given an oral chlorpromazine dose of 100 mg three
      times daily, and plasma concentrations of chlorpromazine were measured weekly.
      This dose was well tolerated during the first week of therapy. In the second week
      the patient took a combined oral contraceptive; this was followed by severe
      dyskinesias and tremor. Plasma chlorpromazine levels were found to be about
      sixfold higher than those in the first week, although the dose of chlorpromazine
      had not changed. This observation suggests that the oral contraceptive increased
      the plasma concentration of chlorpromazine.

PMID- 11591905
TI  - From beach to bedside: history of the development of sirolimus.

PMID- 11591906
TI  - Therapeutic drug monitoring-guided high teicoplanin dosage regimen required to
      treat a hypoalbuminemic renal transplant patient undergoing continuous venovenous
      hemofiltration.

PMID- 11591907
TI  - [Fifty-two cases of postoperative endophthalmitis treated with one protocol:
      anatomical and functional results].
AB  - PURPOSE: To evaluate our management of postoperative endophthalmitis and compare
      our protocol to the Endophthalmitis Vitrectomy Study's (EVS) recommended
      protocol. PATIENTS AND METHODS: This study comprises 52 patients with
      postoperative endophthalmitis treated with the same protocol in 1996 and 1997.
      Patients were given an intravitreal injection of antibiotics (vancomycin
      amikacin) and steroids (dexamethasone), systemic antibiotics (pefloxacin
      piperracillin), and systemic steroids in bolus. Vitrectomy was not systematic. So
      as not to delay the treatment, cultures were obtained only from an anterior
      chamber paracentesis. RESULTS: Visual acuity was measurable in 86.5% of the
      patients, with 20/100 in 63.4% and 20/40 in 44.2%. Our results are similar to
      those of the EVS even when initial visual acuity was Light Perception.
      CONCLUSION: Our protocol is simple and easy to perform in all ophthalmology
      centers. It is based on intravitreal injection, which must be performed as
      quickly as possible.

PMID- 11591908
TI  - [Change in refraction and topography after penetrating keratoplasty suture
      removal].
AB  - PURPOSE: To study the refractive and topographic modifications induced by
      penetrating keratoplasty suture removal. METHODS: We prospectively studied 80
      corneas from 80 patients who had undergone penetrating keratoplasty. All of the
      eyes were examined before and after all sutures were removed, respectively at
      10.9 5.1 months and 21.5 9.6 months after keratoplasty. Subjective refraction,
      best spectacle-corrected visual acuity (LogMAR units), keratometry, and corneal
      topography using the EyeSys 2000((R)) device (axial tangential and refractive
      power) were recorded. Topographies were classified according to the pattern
      (Bogan classification) and the asphericity shape (prolate and oblate). RESULTS:
      Best spectacle-corrected visual acuity (Log MAR units) increased significantly
      after suture removal (1.1 1.9 lines, plt; 0.001). Suture removal decreased the
      subjective cylinder (5.01 D 2.06 with suture, 4.11 2.08 without suture; p=0.009).
      The change in subjective cylinder correlated with the change in topographic
      pattern(s)=0.67 p<0.001). Conversely to the "bow tie" patterns, the other
      topographic patterns were more frequent after suture removal. The change in
      visual acuity was essentially explained by the change in subjective
      cylinder(s)=0.40 p=0.002). The average central corneal power decreased
      significantly after suture removal by 0.83 to 1.81 D (p<0.001), whereas the
      subjective spherical equivalent increased (hyperopization) (-4.07D 3.73 with
      suture, -3.48 3.40 without suture; p=0.02). The change in central corneal power
      significantly correlated with the change in subjective spherical equivalent
      (r(s)()>0.30 plt; 0.001). The corneal power of the mid-periphery did not
      significantly change after suture removal. Suture removal significantly modified
      the asphericity shape distribution. (majority of prolate shape with suture,
      majority of oblate shape without suture, p<0.001). CONCLUSION: Keratoplasty
      sutures induce a central bulge in the corneal graft. Suture removal induces a
      decrease in the subjective cylinder and it increases the subjective spherical
      equivalent (hyperopization) through a decrease in the central corneal power.
      Suture removal modifies the corneal topographic pattern and shape. Visual acuity
      improvement after suture removal is mainly explained by the decrease in
      subjective astigmatism.

PMID- 11591909
TI  - [Cataract in uveitis patients: extracapsular and intraocular posterior
      implantation results. A retrospective study of 14 eyes].
AB  - PURPOSE: Checking visual results and progression after cataract surgery in
      uveitis patients. METHODS: Fourteen eyes of 13 patients were retrospectively
      studied after cataract extraction from December 1993 to April 1997. We describe
      the surgical procedure followed by the visual outcome of cataract surgery,
      complications, and treatment. RESULTS: Specific uveitic syndromes were determined
      in eight patients. Fuchs' heterochromic iridocyclitis was the cause in three
      cases, ankylosing spondylitis in one case, sarcoidosis in two cases,
      toxoplasmosis in one case and Birdshot chorioretinopathy in one case.
      Phacoemulsification was performed in 10 eyes and a manual extracapsular procedure
      in four eyes. Posterior chamber implantation was performed in 13 cases. Final
      visual acuity improved in 64% cases, from 1 to 8 lines (average 3.5). Eight eyes
      had visual acuity worse than 5/10, attributed to posterior segment abnormalities,
      in particular macular edema, which is the main limiting factor of optimal visual
      recovery. Capsular opacification was the most frequent complication in the
      anterior segment. Endophthalmitis was described in one patient. CONCLUSION:
      Visual results of cataract surgery depend on different uveitic entities and on
      posterior segment abnormalities. Results are generally successful when uveitis is
      not severe and the posterior segment can be carefully observed after cataract
      surgery. Extracapsular cataract extraction and posterior chamber implantation
      seem to be well tolerated if inflammation is perfectly under control before
      surgery.

PMID- 11591910
TI  - [Ocular biometric measurements with a slit-lamp method (Orbscan)].
AB  - PURPOSE: To evaluate the accuracy and reproducibility of the biometric
      measurements obtained with the Orbscan((R)) device in normal eyes. METHODS:
      Anterior chamber depth, axial length, and corneal diameter were studied in 50
      normal eyes of 25 patients using the Orbscan((R)) device and A-Scan
      ultrasonography. For each eye, two exams were done successively and
      reproducibility was calculated by analyzing the difference between both
      measurements. RESULTS: The reproducibility of anterior chamber depth and corneal
      diameter measurements obtained by Orbscan((R)) was high (respectively 0.721.25%
      and 0.831.40%). The anterior chamber depth measurements by Orbscan((R)) and A
      Scan ultrasonography were strongly correlated (rs=0.92;p<0.001). The axial length
      measurement obtained with the Orbscan((R)) device was less reproducible
      (3.554.11%). For the axial length, the Orbscan((R)) measurements and A-Scan
      ultrasonography measurement was poorly correlated. (rs=0.64; p<0.001).
      CONCLUSION: The anterior chamber depth measurement obtained with the Orbscan((R))
      device showed high reproducibility and it was strongly correlated with the
      measurement obtained by A-Scan ultrasonography. Axial length measurement obtained
      with the Orbscan((R)) device was less reproducible and poorly correlated with the
      A-Scan ultrasonography measurement. It was not relevant for clinical application.

PMID- 11591911
TI  - [Surgery for choroidal subfoveal neovascularization in patients with severe
      myopia. Retrospective analysis of 17 patients].
AB  - Treatment of choroidal neovascularization in pathological myopia is still
      controversial. METHODS: A retrospective analysis of 17 patients with severe
      myopia (>-6) and subfoveal choroidal neovascularization who underwent surgical
      removal of choroidal neovascularization, was performed. The patient population
      consisted of 2 groups: 9 patients younger than 50 years and 8 patients older than
      50 years. All the patients underwent vitrectomy with surgical removal of
      subfoveal choroidal neovascularization. RESULTS: We reviewed the postoperative
      clinical and angiographic findings. In group I, visual acuity improved in 4 eyes
      (44%), remained unchanged in 4 eyes (44%) and decreased in one eye. In group II,
      none of the patients had visual improvement, visual acuity remained unchanged in
      6 eyes (71%), and decreased in 2 eyes. CONCLUSION: The visual outcomes in most
      patients in this series were better than their natural history. Surgical removal
      of subfoveal choroidal neovascularization associated with severe myopia may
      provide visual benefit in young patients. A prospective, randomized clinical
      trial is necessary to determine the place of this surgical procedure.

PMID- 11591912
TI  - [Tarsomarginal graft. Indication and results in palpebral surgery].
AB  - A tarsomarginal graft is indicated in eyelid reconstructive surgery particularly
      after tumor resection. We reported the results of a retrospective study during
      the past 13 years with 58 grafts. We found a predominance of basal cell
      carcinomas localised in the lateral third portion of the lid (42%) and in the
      lower eyelid (76%). The mean size was 14mm for the tumor and 9.81mm for the
      graft. Grafts were used to cover a defect larger than 5mm. Complications were
      rare, and mainly involved suture looseness. The Hubner technique gave good
      results; repairing the eyelid without having to make a tarsorraphy and providing
      good cosmetic results. The graft must be covered by a skin flap.

PMID- 11591913
TI  - [Effectiveness of conjunctival autograft transplantation in pterygium surgery].
AB  - INTRODUCTION: Pterygium is a fibrovascular overgrowth of bulbar cunjonctiva over
      the cornea and may produce visual impairment. Many surgical techniques and
      adjunctive therapies have been proposed but recurrence remains frequent.
      MATERIALS AND METHODS: We report a prospective study of 52 eyes treated by limbal
      conjunctival autograft for primary and recurrent pterygium. We compare our
      results with the technique of simple excision performed in 111 cases of pterygium
      (3 being a recurrent pterygium). RESULTS: The mean age of the patients was 45
      years. 30 cases of pterygium were primary (57.7%) and 22 were recurrent (42.3%).
      After an average follow-up of 14 months, the incidence of recurrence was 10%.
      Only 2 of these recurrent cases of pterygium were primary. DISCUSSION:
      Conjunctival autograft is a simple, safe, and highly effective procedure for the
      treatment of pterygium. It reduces the rate of recurrence more than simple
      excision (55.9% after a follow-up of 1 year). CONCLUSION: The introduction of
      limbal conjunctival autograft for the treatment of pterygium meets three main
      goals: safety, good optical outcome and a lower rate of recurrence. This
      procedure could be accepted as a successful technique for cases with recurrent
      pterygium specially in younger patients and when the environment al factors lower
      the development of recurrent pterygium.

PMID- 11591915
TI  - [Corneal crystalline deposits in monoclonal gammapathy: a report of two cases].
AB  - Corneal immunoglobulin deposits are an unusual complication of
      lymphoproliferative affections such as monoclonal gammapathy of indeterminate
      significance, essential cryoglobulinemia, or multiple myeloma. Although uncommon,
      this crystalline keratopathy may be the first clinical sign of these malignant
      disorders. We report two cases of paraproteinic crystalline keratopathy: the
      first case is associated with a multiple myeloma, combined with cryoglobulinemia,
      and the second case with monoclonal gammapathy of indeterminate significance. In
      both cases, corneal crystalline deposits appeared before general clinical
      symptoms. In the first case, the systemic therapy made no change in the
      biomicroscopic aspect of the corneal deposit, despite immunoglobulin level
      normalization in the serum. Conversely, in the second case, we noticed a
      substantial regression of the corneal crystalline deposits as the systemic
      normalization. A review of the literature clarified the variety of clinical dorms
      of paraproteinic crystalline keratopathy, the physiopathogenics hypotheses that
      are currently being discussed, and the possible therapeutic modalities.

PMID- 11591914
TI  - [Idiopathic polypoidal choroidal vasculopathy leading to blindness].
AB  - Idiopathic polypoidal choroidal vasculopathy (IPCV) has recently been recognized
      as a distinct cause of recurrent subretinal hemorrhages and exudates as well as
      multiple hemorrhagic retinal pigment epithelium detachments in the macula. IPCV
      is usually considered to have a good visual prognosis. We report the case of a 44
      year-old woman with particularly severe bilateral macular and peripheral IPCV.
      The patient was followed for 13 years and had final visual acuity of counting
      fingers in the right eye and 20/400 in the left eye. Patients with IPCV with
      macular choroidal neovascularization tend to have a poor visual prognosis. This
      case of IPCV should alert the physician to be particularly attentive to the
      follow-up of these patients.

PMID- 11591916
TI  - [Myelinated nerve fibers associated with cilioretinal artery occlusion].
AB  - Although the myelinated nerve fibers are considered as benign, cases associated
      with retinal vascular abnormalities (telangiectasis, neovascularization, vascular
      occlusions) have recently been reported, suggesting a possible pathogenic
      correlation between these elements. Our observation presents a 44-year-old
      patient, with a sudden decrease of visual acuity in the right eye, discal and
      peridiscal myelinated nerve fibers, associated with cilioretinal artery
      occlusion. The general clinical and laboratory examination, except for a drug
      stabilized arterial hypertension, did not reveal other local or general embolic
      factors. One year later, the decrease in visual acuity had remained unchanged and
      the area of the myelinated nerve fibers had diminished. Based on the association
      between the myelinated nerve fibers, the cilioretinal artery occlusion, the young
      age of the patient, and the absence of other local or general embolic factors, we
      consider there is a possible pathogenic correlation between these elements. The
      action of the myelinated nerve fibers can be explained by a mechanical
      compression, with the disruption of the cilioretinal artery route, a structurally
      vulnerable artery.

PMID- 11591917
TI  - [Foreign bodies in the anterior segment].
AB  - Foreign bodies in the anterior segment are different from those in the posterior
      segment regarding two specific aspects: they are frequently visible so defining
      their exact position is easier and surgical extraction is thus facilitated and
      the prognosis is better. However, infectious risk remains an important concern,
      especially in the case of an intraocular body, and foreign bodies must be
      considered in every anterior segment would. After an epidemiological review,
      foreign bodies of different anterior segment locations are discussed and surgical
      treatment is considered.

PMID- 11591918
TI  - [False hypopyons].

PMID- 11591919
TI  - [A new instrument in eyelid surgery: ptosis forceps with a protected lock].
AB  - We report on a new instrument in eyelid surgery: the ptosis forceps with a
      protected lock. This new device helps the surgeon to dissect the levator muscle
      to facilitate any type of levator surgery. It is particularly useful in the
      adjustment of the superior lid margin level towards the corneoscleral area in
      ptosis surgery with levator resection.

PMID- 11591920
TI  - [Treatment of retrobulbar optic neuropathy in multiple sclerosis].

PMID- 11591921
TI  - [Allergy to contrast materials does exist! Practical considerations].

PMID- 11591922
TI  - [Breast cancer screening campaign].

PMID- 11591923
TI  - [Value of helical CT in Takayasu arteritis].
AB  - In the past, the diagnosis and course of Takayasu arteritis were monitored by
      following angiographic findings, in addition to clinical symptoms and biological
      tests. More recently, cross-sectional imaging techniques especially Computed
      Tomography (CT) depicted mural changes in aorta and main vessels in this disease.
      Within the same acquisition, spiral mode also allows to show luminal changes,
      similarly to conventional angiography. In addition to its diagnostic value
      especially in the early phase of the disease, CT seems accurate in the follow-up
      of treated patients and may be proposed as a therapeutic guide. CT features are
      presented, according to the stage of the disease and the vessels involved.

PMID- 11591924
TI  - [Severe reactions to iodinated contrast agents: is anaphylaxis responsible?].
AB  - PURPOSE: The etiology of severe reactions following injection of iodinated
      contrast agents is the subject of controversy. No consensus has been established
      regarding the management of patients at risk, risk factors and premedication
      because in most cases published no diagnostic exploration has been carried out on
      patients who have experienced a severe reaction. MATERIAL: and Methods. Diagnosis
      of drug anaphylaxis is based on clinical history, proof of mediator release and
      drug-specific IgE antibodies (when the technique is available) or cutaneous tests
      (when direct technique is not available). RESULTS: This approach has been adopted
      for etiologic diagnosis of 5 clinical cases of severe anaphylactoid reactions
      (including one death) following the injection of ionic and non ionic contrast
      agents. Clinical symptoms, biology and cutaneous tests are consistent with
      anaphylaxis. CONCLUSION: Any patient who has had a severe anaphylactoid reaction
      following injection of a contrast agent should undergo an allergological
      assessment to confirm the diagnosis and identify the culprit contrast agent.
      Indeed, no premedication has proved efficient for the prevention of subsequent
      allergic reactions.

PMID- 11591925
TI  - [Strict anteroposterior radiography of the shoulder: value of the assessment of
      rotator cuff tears].
AB  - PURPOSE: To compare the contribution of various radiographic projections in the
      evaluation of impingement syndrome and rotator cuff tears. Materials and method.
      We realized a prospective study in 53 patients with suspected rotator cuff tear,
      evaluated by plain radiographs and arthrography (gold standard). 31 patients were
      men and 22 were women (mean age 51 years). In all patients, anteroposterior
      radiograph, strict anteroposterior straight-beam decubitus view and
      anteroposterior radiograph during Leclercq's maneuver of the affected shoulder
      were obtained. The population was divided into three groups: group 1: normal
      arthrography (n=19), group 2: isolated supraspinatus tendon tear (n=23), group 3:
      rupture of the supraspinatus and infraspinatus tendons (n=11). The acromio
      humeral space was measured on all these views and differences between the three
      groups were statistically analyzed. RESULTS: There is a significant statistical
      difference between the height of the acromio-humeral space found in patients with
      isolated tear of the supraspinatus tendon and those with a tear extending to the
      infraspinatus tendon (p=0.0001). The ROC methodology showed a better accuracy of
      the strict anteroposterior straight-beam decubitus view in cases of wide ruptures
      of the rotator cuff, and this for a selected threshold value of 6 mm. CONCLUSION:
      Strict anteroposterior straight-beam decubitus view, seems to be easy to realize,
      cheap, reproducible and very powerful in the preoperative assessment of patients
      with suspected rotator cuff tendon tear. It allows an excellent visualization of
      the acromioclavicular joint.

PMID- 11591926
TI  - [Imaging of primary carcinoid tumor of the pancreas].
AB  - PURPOSE: To describe the imaging features of primary carcinoid tumors of the
      pancreas. Materials and Methods. The sonographic and computed tomographic
      examinations of six patients with pathologically proven primary carcinoid tumor
      of the pancreas were retrospectively reviewed. RESULTS: In all cases, sonography
      showed hypoechoic and well circumscribed tumors. CT scan demonstrated
      hypoattenuating tumors on noncontrast images, with variable enhancement on
      postcontrast images. Small tumors (less than 2cm in diameter) were homogeneous
      whereas larger tumors were heterogeneous with areas of cystic necrosis. In two
      cases, enlarged lymph nodes were found in association with ascitis. In one case,
      hepatic metastases were present. CONCLUSION: Primary carcinoid tumors of the
      pancreas display various and non specific imaging features. Small tumors are
      likely to be homogeneous and hypervascular whereas larger tumors are
      heterogeneous and hypovascular.

PMID- 11591927
TI  - [Dosimetry comparison of pelvimetry methods using conventional radiographs and
      CT].
AB  - PURPOSE: To determine the fetal and maternal exposure to radiation by use of
      thermoluminescent dosimeters in order to compare conventional and CT-scan X-ray.
      Materials and methods. Dosimetry was performed with an anthropomorph phantom.
      Thermoluminescent dosimeters were positioned on the surface and in the depth of
      the phantom. Digital radiography of the pelvis was performed according to a
      standard technique. CT-scan of the pelvis was performed according to the
      Buthiau's technique. RESULTS: With CT, the dose reached 0.31 to 4.95 mGy, with a
      dose of 2.32 mGy for the fetal gonads. With standard technique, the doses reached
      0.03 to 0.39 mGy, with a dose of 0.39 mGy for the fetal gonads. CONCLUSION: With
      CT the fetus and the mother were exposed to 1/10th of the total dose delivered
      using conventional X-rays and the dose distribution was more homogenous.

PMID- 11591928
TI  - [Bile duct papillomatosis: unrecognized preoperative diagnosis].
AB  - The diffuse biliary or pancreatic papillomatosis is a rare pathology. Reported
      cases in the literature underscore the difficulties of preoperative diagnosis of
      these lesions, their extensive nature, their tendency to relapse, and their
      malignant potential. The case that we report differs by the isolated involvement
      of the biliary tract and by the increasing role of imaging (MRCP) for diagnosis
      and follow-up.

PMID- 11591930
TI  - [Traumatic atlanto-occipital dislocation with regressive tetraparesia].
AB  - We report a case of traumatic atlantooccipital dislocation in a 31 year old
      woman, with regressive quadriparesia after orthopedic stabilization.

PMID- 11591929
TI  - [Calcific retropharyngeal tendinitis: unusual diagnosis].
AB  - Acute calcific retropharyngeal tendinitis is a rare entity that often is
      initially misdiagnosed a retropharyngeal abscess and treated with IV
      administration of antibiotics. In our 2 cases, imaging enabled a correct
      diagnosis to be made. Two patients were admitted to the hospital with dysphagia,
      severe neck discomfort and fever. Lateral radiographs of the cervical spine and
      CT were obtained in both cases, while MRI was obtained in one case. Calcification
      of the prevertebral muscles was demonstrated by CT in both cases, and detected on
      lateral radiographs in only one case. Soft tissue swelling was noted at CT and
      MRI. A clinical diagnosis of calcific retropharyngeal tendinitis may be difficult
      to achieve and a definitive diagnosis can be confirmed at imaging studies.

PMID- 11591931
TI  - [Fluid-fluid level in a non functioning and hemorragic neuro-endocrine islet-cell
      tumor of the pancreas: MRI features].
AB  - The authors report the MR features of a non functioning and hemorragic islet-cell
      tumor of the pancreas. This tumor was composed of a central cystic component with
      a fluid-fluid level seen on T1- and T2-weighted images and a peripheral
      hypervascular soft tissue component which showed hyperintensity on T2-weighted
      images with fat saturation.

PMID- 11591932
TI  - [Sural false aneurysm disclosing the presence of Behcet's disease].
AB  - The authors report the case of a 35 year old patient that presented acutely with
      a false aneurysm of the tibioperoneal trunk diagnosed at Doppler US and CT
      angiography. Behcet's disease was considered because of a prior history of
      recurrent phlebitis, the presence of bipolar aphthae and a biological
      inflammatory syndrome. This case is of interest for two reasons: first, the
      atypical location of the false aneurysm, and second, the value of less invasive
      imaging techniques, namely Doppler US and CT angiography.

PMID- 11591933
TI  - [Quid? Capillary leak syndrome].

PMID- 11591936
TI  - Laparoscopic hepatectomy for hepatocellular carcinoma.
AB  - BACKGROUND: No reports exist on the role of laparoscopic hepatectomy in the short
      and long-term outcomes of patients with hepatocellular carcinoma (HCC). We
      present our results from using laparoscopic hepatectomy for HCC and discuss the
      importance of this procedure. METHODS: To investigate the role of laparoscopic
      hepatectomy in the short- and long-term outcomes, 17 patients with HCC who
      underwent laparoscopic hepatectomy (laparoscopic hepatectomy group) were compared
      with 38 patients who underwent conventional open hepatectomy (open hepatectomy
      group) during the same period. RESULTS: No differences in operation time, blood
      loss, rate of blood transfusion, or incidence of postoperative complications were
      found between the two groups. The postoperative hospital stay for the
      laparoscopic hepatectomy group was significantly shorter than for the open
      hepatectomy group. With long-term prognosis, no difference was found in survival
      rate and disease-free survival rate between the two groups. No recurrence was
      found in the stump of the remaining liver after laparoscopic hepatectomy.
      CONCLUSIONS: Laparoscopic hepatectomy has resulted in a better short-term outcome
      after surgery than conventional open hepatectomy. The long-term prognosis in the
      laparoscopic hepatectomy group was similar to that in the open hepatectomy group.
      Therefore, laparoscopic hepatectomy can be a new alternative for treatment of
      cirrhotic patients with HCC when patients are strictly selected.

PMID- 11591937
TI  - Laparoscopically assisted resection of choledochal cyst and Roux-en-Y
      reconstruction.
AB  - Laparoscopic surgery for a congenital choledochal cyst was accomplished in five
      of eight adult patients for whom it was attempted (63%). Creation of a Roux-en-Y
      jejunal limb by midline minilaparotomy and hepaticojejunostomy using a
      laparoscopic sewing instrument facilitated the procedure. BACKGROUND: Congenital
      choledochal cyst is a good indication for laparoscopic surgery. However, only two
      case reports are available at this writing. METHODS: Eight adult patients, ages
      19 to 61 years (mean, 32.6 years), underwent laparoscopically assisted resection
      of the choledochal cyst and Roux-en-Y hepaticojejunostomy. RESULTS: The whole
      procedure was accomplished in five patients (63%). The duration of the procedure
      ranged from 525 to 680 min (average, 616 min). Open conversion in three patients
      was necessitated by severance of a small common hepatic duct because of
      disorientation caused by previous laparoscopic cholecystectomy, electrocautery
      injury to the common channel distal to the anomalous pancreaticobiliary junction,
      or heavy adhesion around the cyst secondary to recent severe cholangitis.
      Creation of a Roux-en-Y jejunal limb by midline minilaparotomy and
      hepaticojejunostomy using a laparoscopic sewing instrument facilitated the
      procedure. CONCLUSIONS: Laparoscopically assisted resection of the choledochal
      cyst and hepaticojejunostomy are technically feasible and deserve further
      clinical trials.

PMID- 11591940
TI  - The effects of pneumoperitoneum and patient position on hemodynamics during
      laparoscopic cholecystectomy.
AB  - BACKGROUND: The purpose of this study was to prospectively examine the combined
      effects of pneumoperitoneum and the reverse Trendelenberg position on cardiac
      hemodynamics during laparoscopic cholecystectomy. METHODS: Thirty-nine patients
      undergoing laparoscopic cholecystectomy as performed by a single surgeon were
      enrolled in the study. Hemodynamic data were collected continuously using a
      transthoracic bioimpedance monitor. All patients were subjected to insufflation
      pressures of 15 mmHg. Data were examined using mixed analysis of variance
      (ANOVA). RESULTS: Cardiac index fell 11% with induction of anesthesia (p < 0.05),
      with stroke volume decreasing 7.2% (p < 0.05). Insufflation caused significant
      decreases in stroke volume (SV) left ventricular end diastolic volume (LVEDV) but
      not cardiac index (CI). Placing the patients in the reverse Trendelenberg
      position caused no significant changes in these parameters. There were no
      significant differences between ASA (American Society of Anesthesiologists)
      classes I and II patients when compared to ASA III patients. CONCLUSIONS:
      Patients undergoing laparoscopic cholecystectomy experience significant
      hemodynamic depression. The effect of general anesthesia is the most profound.
      Insufflation of the abdomen caused more mild hemodynamic effects in our study.
      The addition of a reverse Trendelenberg position did not alter the patient's
      hemodynamic status.

PMID- 11591939
TI  - Helium and other alternative insufflation gases for laparoscopy.
AB  - BACKGROUND: Carbon dioxide (CO(2)) is currently the insufflation gas of choice
      for laparoscopy. It fulfills most of the requirements for an ideal insufflation
      gas, being colorless, noninflammable, and rapidly excreted from the circulation.
      However, its use is associated with adverse cardiorespiratory effects, especially
      in patients with preexisting cardiorespiratory compromise. METHODS: The
      descriptive review of relevant literature, moreover, has been proposed that it
      increases the incidence of port site (wound) metastases from abdominal cancers
      when used during oncological surgery. In addition, it may cause postoperative
      pain due to peritoneal irritation, and its use is associated with physiological
      and immunological impairment. Hence, there is scope for the investigation of
      alternative insufflation gases. Other possibilities include gasless laparoscopy,
      helium, nitrous oxide, (N(2)O), and argon. Helium insufflation has been used
      extensively in animal models but only to a limited extent in humans. In
      experimental studies, it has been shown to produce fewer changes in
      cardiorespiratory and intraperitoneal immunological status than CO(2)
      insufflation, and its use is associated with less spread of tumors to port sites
      in a variety of small animal tumor models. However, helium also has the potential
      for some adverse effects. Helium pneumothorax probably resolves more slowly than
      CO(2) pneumothorax, and helium gas embolism is tolerated poorly in animal models.
      The clinical significance of these potential problems has yet to be determined.
      CONCLUSIONS: Although the use of alternative gases appears to be promising,
      further evaluation is needed within both clinical and laboratory settings before
      their routine clinical use can be supported.

PMID- 11591941
TI  - Major and minor injuries during the creation of pneumoperitoneum. A multicenter
      study on 12,919 cases.
AB  - BACKGROUND: Lap Group Roma was established in 1999 to promote and control the
      development of laparoscopic surgery in the area of Rome and its province.
      Complications during the creation of pneumoperitoneum were given a high priority
      of investigation, and a retrospective enquiry was immediately carried out.
      METHODS: A questionnaire about all laparoscopic surgical practice performed from
      January 1994 to December 1998 was sent to the supervisors of 28 centers of
      general surgery in the area of Rome and its province participating to the Lap
      Group Roma, requesting demographics, type of procedure for the creation of
      pneumoperitoneum, type and timing of operation, and major vascular, visceral, and
      minor vascular injuries related to the creation of pneumoperitoneum. RESULTS: The
      questionnaire was returned by 57% of the centers, for a total of 12,919
      laparoscopic procedures. The type of procedure used to create the
      pneumoperitoneum involved a standard closed approach (Veress needle + first
      trocar) in 82% of the cases, an open (Hasson) approach in 9% of the cases, and
      the use of an optical trocar in 9% of the cases. There were seven major vascular
      injuries (0.05%), eight visceral lesions (0.06%), and nine minor vascular lesions
      (0.07%), for an overall morbility of 0.18%. There was no death related to these
      complications. The rate of complications differed significantly (p < 0.0001)
      depending on the type of approach used. It was 0.27% with the optical trocar (3
      of 1,009 cases), 0.18% with the closed approach (20 of 10,664 cases), and 0.09%
      with the open approach (1 of 1,135 cases). CONCLUSIONS: There is no foolproof
      technique for the creation of pneumoperitoneum, and this inquiry confirms the
      need of a constant search for prevention and early treatment of complications
      encountered during this obligatory phase of any laparoscopic approach. A well
      conducted and prolonged prospective audit of clinical practice could help in
      identifying the risk factors that can make an alternative approach (open or video
      controlled) preferable to the widely used closed approach.

PMID- 11591942
TI  - Use of the optical access trocar for safe and rapid entry in various laparoscopic
      procedures.
AB  - BACKGROUND: The use of the Veress needle in laparoscopy to create the
      pneumoperitoneum has inherent risks; it may cause vascular and visceral injuries.
      The open technique is compromised by the leakage of carbon dioxide and can also
      be time consuming. One alternative is to enter the abdomen using an optical
      trocar under direct view. Our aim was to determine whether the optical access
      trocar can be used to effect a safe and rapid entry in various laparoscopic
      procedures. METHODS: Over a 4-year period, the Optiview trocar was used for
      initial entry in 650 laparoscopic procedures. The procedures included
      cholecystectomy (n = 282), transabdominal inguinal hernia repair (n = 76),
      radiofrequency ablation of liver tumors (n = 73), adrenalectomy (n = 54),
      appendectomy (n = 41), colorectal surgery (n = 39), and various other procedures
      (n = 85). The following parameters were analyzed: presence of previous abdominal
      operations, site and duration of entry, and complications. RESULTS: Of the 650
      patients, 156 (24%) had had previous abdominal operations. In 25 cases, previous
      trocar sites were reused for optical access. The optical trocar was inserted at
      the umbilicus in 495 patients (76%), in the right upper quadrant in 77 (12%), in
      the left upper quadrant in 26 (4%), in the upper midline in eight (1%), in the
      right lower quadrant in six (0.9%), and in the left lower quadrant in three
      (0.5%). In 35 patients undergoing posterior adrenalectomy, optical trocars were
      used to enter Gerota's space. Mean (SD) entry times were 92 (45) sec at the
      umbilical site, 114 (30) sec at the back, and 77 (35) sec at the remaining sites.
      Complications (0.3%) included one injury to the bowel and one injury to the
      gallbladder; however, they were recognized and repaired immediately. CONCLUSIONS:
      To our knowledge, this report comprises the largest series in which the optical
      access trocar was used for laparoscopic surgery. This device provides the basis
      for a safe and fast technique for initial trocar placement: it also has the
      potential to reduce costs. Thanks to our favorable experience, the optical trocar
      method has become the standard technique for abdominal access in our laparoscopic
      practice since 1995.

PMID- 11591943
TI  - Improved functional outcome and more rapid return to normal activity following
      laparoscopic hernia repair.
AB  - BACKGROUND: The laparoscopic repair of inguinal hernias remains a controversial
      subject. Advantages in terms of reduced postoperative pain and improved
      functional status have been demonstrated in some studies and refuted in others.
      We performed a prospective study of a group of young healthy patients to measure
      pain levels and time to return to normal activity following totally
      extraperitoneal laparoscopic (TEP) hernia repair and compared these outcomes to
      those seen following conventional anterior repair. METHODS: A total of 151
      patients were entered into a prospective nonrandomized study. Forty-eight
      patients underwent anterior repair; 103 underwent TEP repair. Patients were
      followed at 2 and 6 weeks to assess their level of function on a five-point
      scale. Their use of pain medication was also assessed, and total days away from
      work and days until return to full activity were documented. RESULTS: The open
      group returned to work at 11.5 days and to full activity at 26.7 days. The TEP
      group returned to work at 6.4 days and to full activity at 14.2 days (p < 0.001
      for both data). There was no statistically significant difference in the use of
      pain medication. The TEP group reported better functional status at 2 weeks than
      the open group. At 6 weeks, this difference was no longer statistically
      significant. CONCLUSION: As compared to conventional open repair, TEP hernia
      repair offers advantages in postoperative function and an earlier return to full
      activity.

PMID- 11591944
TI  - A randomized controlled trial to determine the effect of humidified carbon
      dioxide (CO2) insufflation on postoperative pain following thoracoscopic
      procedures.
AB  - BACKGROUND: It has previously been shown that the insufflation of humidified gas
      during laparoscopy results in less postoperative pain than is observed following
      the use of dry gas. Experimental evidence also suggests that dry gas insufflation
      during thoracoscopy results in greater structural injury to the pleura than
      occurs with the use of humidified gas. The present study was designed to
      determine the effect of humidified gas insufflation on postoperative pain
      following thoracoscopic procedures. METHODS: Forty consecutive patients were
      prospectively randomized. Twenty patients were insufflated with humidified carbon
      dioxide (CO(2)), and 20 control patients received standard dry CO(2). RESULTS:
      The patients' analogue pain score was significantly lower following humidified
      gas insufflation compared to dry gas insufflation when assessed at 6 h
      postoperatively, as well as on the 1st, 2nd, 3rd, and 14th postoperative days.
      The postoperative morphine consumption was lower in the humidified group than it
      was in the control group. The incidence of respiratory complications was
      identical for both groups. CONCLUSION: The use of humidified gas appears to
      reduce postoperative pain but not the rate of respiratory complications.

PMID- 11591945
TI  - Laparoscopic inguinal hernia repair.
AB  - BACKGROUND: We performed a prospective study to evaluate the safety and efficacy
      of laparoscopic hernia repair in our hospital. METHODS: A total of 2500
      consecutive laparoscopic transabdominal hernia repairs (TAPP) were performed in
      1952 patients. Their average age was 59 years. We used a mesh. 12 x 15cm.
      RESULTS: The average operating time was 32 mins. We had a recurrence rate of
      1.04%. There were 89 complications (3.56%). Three were bladder injuries, one of
      which necessitated conversion to an open laparotomy. Three of 38 hematomas
      required open exploration. Three patients were reoperated because of nerve
      irritation. An incarcerated trocar hernia occurred in six cases. There was one
      wound infection at the umbilical incision. There were no infections or
      incompatibility reactions at the mesh. The complication rate declined over time.
      At the same time, the rate of recurrence decreased as we acquired more experience
      in laparoscopic hernia repair. CONCLUSION: Laparoscopic hernia repair can be
      performed safely, with low rates of recurrences and few complications are low.
      This technique achieves good results combined with the benefits of minimal
      invasive procedures.

PMID- 11591946
TI  - The impact of gas laparoscopy on abdominal plasminogen activator activity.
AB  - BACKGROUND: The impairment of intestinal perfusion following induction of a
      pneumoperitoneum may lead to a reduction of peritoneal tissue plasminogen
      activator (tPA) activity and a concomitant increased risk of adhesion formation.
      METHODS: Pigs were laparotomized to take peritoneal biopsy specimens from the
      cecum, the ileum, and the abdominal wall. A 15 mmHg pneumoperitoneum was
      established for 3 h by the insufflation of carbon dioxide (group 2, n = 6) or
      helium (group 3, n = 6). Group 1 (n = 7) received no gas insufflation. After a 2
      h recovery period, additional tissue samples were harvested. Specific tPA
      activity was then determined in the tissue extracts. RESULTS: During surgery,
      specific tPA activity decreased in all the samples. As compared with the control
      group (100%), this reduction was strongly aggravated in the cecum (-67.6%, p <
      0.05) and the ileum (-70.8%) of the CO2 group but only slightly aggravated in the
      helium group. The parietal peritoneum was not specifically affected by gas
      insufflation. CONCLUSION: The use of a pneumoperitoneum with carbon dioxide
      significantly affects peritoneal tPA activity and thus may represent a stimulus
      for adhesion formation.

PMID- 11591947
TI  - Outpatient laparoscopic adrenalectomy in patients with Conn's syndrome.
AB  - BACKGROUND: [corrected] We set out to record the operative times of an
      experienced laparoscopic team and assess the feasibility of outpatient
      laparoscopic adrenalectomy when optimal anesthesia was also offered to all
      patients. METHODS: The study included 13 patients with aldosterone/cortisone
      hypersecretion and/or adrenal gland tumors, excluding those with
      pheochromocytoma. They had to live within 30 min travel from the hospital, and
      adult company had to be present at home. All patients received general
      intravenous anesthesia with propofol and remifentanil and were given keterolac,
      propacetamol, droperidol, and ondansetron as prophylaxis against postoperative
      pain and nausea. Laparoscopic adrenalectomy was performed by the transabdominal
      lateral flank approach. Postoperatively, all patients were contacted by phone in
      the evening and the next morning. RESULTS: All 13 patients were discharged 3-6 h
      postoperatively. None were readmitted; thus, the day care success was 100%. The
      mean operative time was 38 min (range, 35-112). Patient satisfaction was
      excellent in all but one case, due to pain on the 1st postoperative day.
      CONCLUSION: Laparoscopic adrenalectomy can be a fast operation. It is feasible
      and safe and yields satisfactory results for patients as an outpatient procedure
      when the necessary surgical experience and optimal anesthesia are both available.

PMID- 11591948
TI  - Thoracoscopic splanchnicectomy for the relief of pain due to chronic
      pancreatitis.
AB  - BACKGROUND: Many methods have been advocated for control of pain in patients
      suffering from chronic pancreatitis. Some patients may be considered for
      pancreatic denervation. This study was performed to evaluate the effect of
      thoracoscopic splanchnicetomy (TS) on pain intensity and many of the common daily
      functions in patients with intractable pain due to chronic pancreatitis. METHODS:
      Twenty-four thoracoscopic splanchnicectomies were performed on twenty patients.
      To assess pain severity and the impact of the pain, all patients completed short
      form using 0-10 numeric rating scale. To describe and compare the adequacy of
      analgesic management before and after TS the Pain Management index was used.
      Patients were evaluated one day prior to the operation and on monthly basis for 6
      months after the procedure. RESULTS: Pain was reduced after the operation
      significantly (p <0,001) and all but four patients had consistent pain relief
      during the postoperative follow-up. Four patients had recurrence of pain 3 months
      after left- sided TS; after undergoing TS on the opposite side, they were
      relieved of pain. The degree to which pain interfered common daily functions
      decreased significantly (p < 0,001) after surgery, and the adequacy of the
      analgesic management improved. CONCLUSIONS: Thoracoscopic splanchnicectomy is a
      simple, minimally invasive, save procedure that appears to offer relief from
      pain, allow recovery of daily activities and improve the adequacy of the
      analgesic management.

PMID- 11591949
TI  - Gasless laparoscopic-assisted ileostomy or colostomy closure using an abdominal
      wall-lifting device.
AB  - BACKGROUND: Restoration of intestinal continuity in patients with ileostomy after
      total colectomy or with colostomy after Hartmann's procedure is a major
      operation. Herein we illustrate the validity of gasless laparoscopically assisted
      reversal using abdominal wall lifting. METHODS: The operation was performed on 10
      patients from February 1997 to May 1999. Seven of them had a left iliac stoma
      after a Hartmann resection, and three had an ileostomy after total colectomy.
      RESULTS: The laparoscopic reversal was completed in eight patients; the two
      others were converted to an open procedure. Three major complications occurred
      (30%). There were no deaths. The average operation time was 192 min (range, 125
      265). Time of discharge from surgery averaged 9.5 days. Mean follow-up of these
      patients was 12 months and negative. CONCLUSIONS: Laparoscopically assisted ileo-
      or colorectal anastomosis without pneumoperitoneum and using a laparotenser can
      be considered for the reversal of patients with ileostomy or colostomy. Even
      taking the high rate of intraoperative or postoperative complications into
      consideration, the advantages that make such a laparoscopic approach suitable
      include reduced trauma related to a second major abdominal operation, reduced
      postoperative pain, and fewer cutaneous tissues exposed to bacterial
      contamination. Moreover, the use of a laparotenser makes it possible to operate
      on elderly patients with cardiovascular diseases. In the absence of
      pneumoperitoneum, it becomes possible to use traditional instruments, with a
      consequent reduction in costs.

PMID- 11591950
TI  - Cellular and humoral inflammatory response after laparoscopic and conventional
      colorectal resections.
AB  - BACKGROUND: Surgical trauma and anesthesia are known to cause transient
      postoperative suppression of the immune system. In randomized controlled trials,
      it has been shown that laparoscopic colorectal resections have short-term
      benefits not observed with conventional colorectal resections. We hypothesized
      that these benefits were due to the reduction in surgical trauma, leading to a
      diminished cytokine response and less depression of cell-mediated immunity after
      laparoscopy. METHODS: In a prospective randomized trial, colorectal cancer
      patients without evidence of metastatic disease underwent either laparoscopic (n
      = 20) or conventional (n = 20) tumor resection. Postoperative immune function was
      assessed by measuring the white blood cell (WBC) count, the CD4+ and CD8+
      lymphocytes, the CD4+/CD8+/ratio, and the HLA-DR expression of CD14+ monocytes.
      In addition, the production of interleukin-6 (IL = 6) and TNF-a were measured
      after ex vivo stimulation of mononuclear blood cells with lipopolysaccharide
      (LPS) and compared to the plasma levels of these cytokines. Postoperative mean
      levels of the immunologic parameters for the two groups were calculated and
      compared using the Mann-Whitney U test. RESULTS: Preoperatively, there were no
      differences between the two groups in terms of patient characteristics or
      immunologic parameters. Although the postoperative peak concentrations of white
      blood cells were significant lower in the laparoscopic group than the
      conventional group (p < 0.05), there were no differences between the two groups
      in the subpopulation of lymphocytes (CD4+, CD8+). HLA-DR expression of CD14+
      monocytes was lower in the conventional group on the 4th postoperative day (p <
      0.05). The laparoscopic group showed higher values in cytokine production of
      mononuclear blood cells after LPS stimulation. Postoperative plasma peak
      concentrations of IL-6 and TNF-a were lower after laparoscopic resection.
      CONCLUSION: Postoperative cell-mediated immunity was better preserved after
      laparoscopic than after conventional colorectal resection. Cellular cytokine
      production was preserved only in the laparoscopic group, while cytokine plasma
      levels were significantly higher in the conventional group. These findings may
      have important implications for the use of laparoscopic colorectal resection,
      especially in patients with malignant disease.

PMID- 11591951
TI  - Carbon dioxide pneumoperitoneum reduces levels of TNF-a mRNA in the brain, liver,
      and peritoneum in mice.
AB  - BACKGROUND: Cytokines are important regulators of the biological response to
      surgical stress. The aim of this study was to determine whether the CO(2)
      pneumoperitoneum would change the expression of TNF-a mRNA in the visceral
      organs, including the brain, in mice. METHODS: Mice were randomly assigned to one
      of six groups: control, anesthesia alone, insufflation with carbon dioxide,
      insufflation with air, laparotomy by short incision, or laparotomy by long
      incision. The brain, liver, jejunum, and peritoneum were harvested either 3 or 24
      h after surgery. Levels of TNF-a mRNA in each tissue was measured by
      semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).
      RESULTS: The air insufflation group showed higher TNF-a mRNA levels in the brain
      and liver than the short-incision group. Levels of TNF-a mRNA in the brain,
      liver, and peritoneum were lower in the CO(2) pneumoperitoneum group than in the
      air insufflation group. Plasma IL-6 and catecholamine in the urine were lower in
      the CO(2) pneumoperitoneum group than the air insufflation group. CONCLUSION:
      Reduced synthesis of TNF-a in the visceral organs, including the brain, is
      correlated with a less marked biologic response to laparoscopic surgery.

PMID- 11591952
TI  - Mini-laparoscopic cholecystectomy vs laparoscopic cholecystectomy.
AB  - BACKGROUND: We set out to assess the safety and efficacy of mini-laparoscopic
      cholecystectomy (MLC) in uncomplicated situations. METHODS: MLC was performed on
      30 consecutive selected patients (< 60 years old, ASA I-II, uncomplicated
      cholecystectomy) with one 12-mm and three 3-mm ports. The total operating time,
      conversion rate, degree of postoperative pain, duration of postoperative hospital
      stay, complications, and cosmetic results were all reviewed and compared with 30
      cases of consecutive conventional laparoscopic cholecystectomy (LC). RESULTS:
      None of the patients in either group required conversion to open cholecystectomy.
      No complications were observed. The operating time and duration of hospital stay
      were similar in both groups. The level of postoperative pain was lower in the MLC
      group (p < 0.001). More patients in the MLC group expressed satisfaction with the
      cosmetic result (p < 0.05). CONCLUSIONS: MLC was shown to be feasible in
      uncomplicated situations. Furthermore, it was associated with less pain and
      produced better cosmetic results than conventional LC. Randomized studies are
      still needed to confirm these findings.

PMID- 11591953
TI  - Laparoscopic autopsies.
AB  - BACKGROUND: In recent years, autopsy consent rates have fallen nationwide. In our
      institution they have declined from 15% to 7% in 10 years. We perceived that
      family reluctance to grant permission for autopsy was related to the invasiveness
      of the open procedure, so we began to do autopsies by needle biopsy, with an
      increase in consents to 25% during the first year. However, the procedure is
      inherently inaccurate, so we recently have introduced minimally invasive
      laparoscopic autopsy. METHODS: From July through October 1999, needle biopsy was
      performed on 25 patients who died at our institution, which was followed by
      laparoscopic evaluation. Consent for full conventional autopsy had been granted
      in nine cases, and these then were performed. Data from these autopsies were
      compared with those from the laparoscopic procedures. RESULTS: Of the patients
      for whom consent was obtained for open autopsy, there was complete agreement as
      to cause of death between the laparoscopic and conventional procedures. In one
      case, a liver hemangioma was missed by laparoscopy, and in two other cases, colon
      polyps were not discovered. Biopsies of internal organs were accurately performed
      on the pancreas, kidneys, and adrenals, all of which had been troublesome for
      needle biopsy alone. CONCLUSIONS: Laparoscopic autopsy is much more acceptable to
      the families of patients than the conventional form, resulting in a higher
      consent rate. On the basis of our study group, this procedure provides accurate
      data concerning the cause of death. In addition, performing these autopsies gives
      surgical residents invaluable training in laparoscopic skills.

PMID- 11591954
TI  - Laparoscopic-assisted formation of a colon neovagina.
AB  - We report the laparoscopic formation of a colon neovagina following radical
      hysterectomy with subtotal colpectomy and radiotherapy in a 43-year-old woman who
      wished to resume normal vaginal sexual intercourse. The rectum was transected by
      a laparoscopic stapling device, preserving the inferior mesenteric and the
      superior rectal artery. By suprapubic mini-laparotomy, the rectosigmoid colon was
      eventerated and transected 8 cm above the staple line. Following colorectal
      anastomosis, the isolated bowel segment was rotated 180 degrees and placed on the
      right side of the anastomosis. A 12-mm trocar was introduced, transvaginally, and
      the isolated bowel segment was sutured to the vaginal resection margin. There
      were no peri- or postoperative complications. Six months after surgery, a
      stenotic area at the entrance to the neovagina was incised. At 12 months after
      primary surgery, the neovagina allowed normal sexual activity. Laparoscopically
      assisted formation of a colon neovagina is a surgical alternative for vaginal
      reconstruction that can be performed successfully even in irradiated patients.

PMID- 11591955
TI  - An overview of videostreaming on the Internet and its application to surgical
      education.
AB  - The Information Age has endowed mankind with a wealth of new technologies.
      Applications of these technologies are being developed to facilitate content
      exchange between individuals and institutions. Internet streaming is an exciting
      new technology that allows multimedia content to be stored and sent over the
      Internet, and medical educators are challenged to harness the potential of
      streaming for educational enhancement. This article helps to define streaming,
      examining its potential for surgical education.

PMID- 11591956
TI  - A versatile tool for exposure in minimally invasive surgery.
AB  - BACKGROUND: Endoscopic surgery in a major cavity in the body requires space for
      manipulation and presentation of the target organ or site. For coronary artery
      grafting on the working heart, additional local cardiac wall immobilization is
      indispensible. METHODS: A passive hydraulic arm was developed to be mounted on
      the operating table rail. The development focused on the arm's versatility,
      durability, flexibility in manipulation, and extreme stiffness when in position.
      RESULTS: The arm was flexible and easy to manipulate. The tip did not move during
      tightening, and the arm was stiff once tightened. The arm was successfully used
      in small and full access beating heart coronary bypass grafting, through the
      latter(i.e., sternotomy) for multivessel revascularization. Immobilization and
      presentation were achieved by suction fixation, allowing accurate anastomosis
      suturing. CONCLUSIONS: The arm enabled effective target site presentation and
      stabilization on the working heart. According to these observations, it may be
      useful as a basic tool for endoscopic surgery.

PMID- 11591958
TI  - The routine use of diagnostic laparoscopy in the intensive care unit.
AB  - BACKGROUND: Delay in the diagnosis of intraabdominal pathology is a major
      contributor to the morbidity and mortality of intensive care unit (ICU) patients.
      Laparoscopy is a valuable diagnostic tool that can be used safely and efficiently
      in the evaluation of intraabdominal processes that may be difficult to diagnose
      with conventional methods. Our goal was to show that laparoscopy performed at the
      bedside in the ICU could be used as a routine diagnostic tool in the evaluation
      of critically ill patients, just as computed tomography (CT), ultrasonography
      (US), and radiography are. METHODS: We present 11 patients who underwent 12
      bedside examinations in the ICU of a community teaching hospital. Several
      different surgeons with varying degrees of laparoscopic experience performed
      these procedures over a 1-year period. RESULTS: Four patients had previously
      undergone recent abdominal operations. Nontherapeutic laparotomy was avoided in
      six patients because of diagnostic laparoscopy. One patient also underwent a
      therapeutic maneuver at the time of diagnostic laparoscopy. None of the patients
      required general anesthesia, although local anesthetics and sedation with
      midazolam or propofol were used. One patient underwent the procedure without
      endotracheal intubation. There were no complications or mortalities directly
      related to the procedure. CONCLUSION: We conclude that bedside laparoscopy in the
      ICU under local anesthesia is a diagnostic and potentially therapeutic tool that
      can be used safely in the work-up of potential abdominal pathology in critically
      ill patients.

PMID- 11591959
TI  - Laparoscopic surgery for inflammatory bowel disease.
AB  - BACKGROUND: Common laparoscopic colorectal procedures in patients with Crohn's
      disease include ileocolic resection and subtotal colectomy. The aim of this study
      was to compare and contrast the results of these two procedures. METHODS:
      Patients who underwent one of these procedures between June 1992 and January 1999
      were identified and included in the study. Statistical analysis was performed
      using the Mann-Whitney test, Student's t-test, or Fisher's exact test. RESULTS:
      In all 109 patients (63 women and 46 men) with an average age of 36.7 years
      (range, 15-74) underwent ileocolic resection (ICR), while 21 patients (16 women
      and five men) with an average age of 36.5 years (range, 18-77) underwent subtotal
      colectomy (STC) (p = NS). There were 14 intraoperative complications, eight (7%)
      in the ICR group and six (29%) in the STC group (p = 0.01). Total operative time
      was 167 min (range, 90-285) in the ICR group and 231 min (range, 140-340) in the
      STC group (p < 0.01). Despite this difference in operating time, the hospital
      stays were very similar at 8.8 days (range, 3-27) and 8.8 days (range, 3-14) (p =
      NS). In 19 (17%) of the ICR patients and five (24%) of the STC patients, their
      procedure was converted to a laparotomy (p = NS). In the ICR group, 20 of the
      patients (18%) had surgery-related postoperative complications, including five
      anastomotic leaks. In the STC group, six of the patients (29%) had surgery
      related complications, including two anastomotic leaks (p = NS). CONCLUSION:
      Although STC is a far more extensive procedure than ICR, the overall
      postoperative complication rate is not significantly different between the two
      groups; however, we found that there were more intraoperative complications
      associated with STC.

PMID- 11591960
TI  - Increased incidence of colorectal adenomas in follow-up evaluation of patients
      with newly diagnosed hyperplastic polyps.
AB  - BACKGROUND: Although adenomatous polyps have been established clearly as
      precursor lesions for most cases of colorectal cancer, the role, if any, of
      hyperplastic polyps remains uncertain. The aim of the current study was to
      determine whether a patient with an index finding of hyperplastic polyp on
      colonoscopy is at increased risk for adenomatous polyps. METHODS: We conducted a
      retrospective cohort study using the records of a single surgeon's colonoscopic
      experience over a 20-year period (June 1973 to December 1994). Patients found to
      have hyperplastic lesions on index colonoscopy were compared with those who had
      "clean" index colonoscopies. The two groups were compared for the subsequent
      diagnosis of adenomatous polyps on follow-up colonoscopies. Those with cancer or
      adenomas at index colonoscopy or in their history were excluded. We used Cox
      proportional hazard modeling with subsequent adenoma or cancer diagnosis at
      follow-up colonoscopy as the outcome, controlling for age and gender. RESULTS: We
      identified 42 patients for whom hyperplastic polyps were the only colorectal
      neoplasms found on the index examination, in contrast to 362 control patients who
      had a "clean" index examination. In this cohort study, patients found to have
      only hyperplastic polyps on initial examination had a rate of subsequent adenoma
      diagnoses (42%) twice that of patients with a clean initial colonoscopy (21%).
      Mean follow-up time was 4.3 years. The relative rate ratio was 2.0 (95%
      confidence interval, 1.2-3.4). CONCLUSIONS: This study suggests that patients
      found to have hyperplastic polyps on initial colonoscopic examination may have
      twice the risk of adenomas on follow-up colonoscopy, as compared with those who
      have clean initial examinations. If this finding is borne out in larger
      prospective studies, surveillance strategies may need to be modified accordingly.

PMID- 11591961
TI  - Sensitivity of double contrast barium enema and colonoscopy for the detection of
      colorectal neoplasms.
AB  - BACKGROUND: Double contrast barium enema (DCBE) is the examination carried out
      most frequently for investigation of patients with large bowel symptoms. The aim
      of this study was to compare the sensitivity of DCBE and colonoscopy for the
      detection of colorectal cancer and neoplastic polyps >/= 1 cm. METHODS: All
      patients undergoing DCBE (1389) or colonoscopy (1081) as the primary
      investigation for large bowel symptoms or for cancer or polyp surveillance in the
      first 9 months of 1997 at a large teaching hospital were included in this study.
      At 1 and 2 years following investigation, a computerized search of appropriate
      diagnosis and procedure codes to detect any missed cancers or polyps was
      performed for all patients with a normal investigation. RESULTS: Almost 19% of
      patients in both groups went on to have an additional large bowel investigation
      over the 2-year period. In the DCBE group, 47 patients (3.5%) had a cancer
      diagnosed; eight of them had been missed at the primary investigation
      (sensitivity 83%). In the colonoscopy group, 37 patients (3.4%) had a cancer; one
      of them had been missed at the primary investigation (sensitivity 97.5%).
      Neoplastic polyps >/= 1 cm were diagnosed in 1.6% of the DCBE group and in 7.7%
      of the colonoscopy group, with sensitivities of 21.7% and 91.4%, respectively.
      Nine patients (0.6%) had a false positive diagnosis of cancer in the DCBE group;
      one had an iatrogenic bowel perforation following flexible sigmoidoscopy.
      CONCLUSIONS: Where adequate facilities and expertise exist, colonoscopy should be
      the investigation of choice for most patients with large bowel symptoms
      suggestive of neoplastic disease.

PMID- 11591962
TI  - Decompressive colonoscopy with intracolonic vancomycin administration for the
      treatment of severe pseudomembranous colitis.
AB  - BACKGROUND: We explored the potential of early decompressive colonoscopy with
      intracolonic vancomycin administration as an adjunctive therapy for severe
      pseudomembranous Clostridium difficile colitis with ileus and toxic megacolon.
      METHODS: We reviewed the symptoms, signs, laboratory tests, radiographic
      findings, and outcomes from the medical records of seven patients who experienced
      eight episodes of severe pseudomembranous colitis with ileus and toxic megacolon.
      All seven patients underwent decompressive colonoscopy with intracolonic
      perfusion of vancomycin. RESULTS: Fever, abdominal pain, diarrhea, abdominal
      distention, and tenderness were present in all patients. Five of seven patients
      were comatose, obtunded, or confused, and six of the seven required ventilatory
      support. The white blood cell count was greater than 16,000 in seven cases (six
      patients). Colonoscopy showed left-side pseudomembranous colitis in one patient,
      right-side colitis in one patient, and diffuse pseudomembranous pancolitis in
      five patients. Two patients were discharged with improvement. Five patients had
      numerous medical problems leading to their death. Complete resolution of
      pseudomembranous colitis occurred in four patients. One patient had a partial
      response, and two patients failed therapy. CONCLUSION: Colonoscopic decompression
      and intracolonic vancomycin administration in the management of severe, acute,
      pseudomembranous colitis associated with ileus and toxic megacolon is feasible,
      safe, and effective in approximately 57% to 71% of cases.

PMID- 11591963
TI  - Comparison of laparoscopic, open, and converted appendectomy for perforated
      appendicitis.
AB  - BACKGROUND: Perforated appendicitis is associated with a significant risk of
      postoperative abdominal and wound infection. Only a few controversial studies
      evaluate the role of laparoscopy in perforated appendicitis. The significance of
      conversion from laparoscopy to open appendectomy for perforated appendicitis is
      not well defined. Statistical analysis was performed using Student's t-test.
      METHODS: Data on 52 patients with perforated appendicitis were prospectively
      collected and retrospectively reviewed. Among these patients, 18 had laparoscopic
      appendectomies (LA); 24 had open appendectomies (OA); and 10 had converted
      appendectomies (CA). The indications for either method were based on the
      attending surgeons's philosophy. Laparoscopic appendectomy was performed using a
      retrograde stapler technique. Operative time, hospital stay, ability to tolerate
      a liquid diet, and postoperative infectious complications were documented.
      RESULTS: No statistically significant difference in the operative time in minutes
      was found between the LA (114 +/- 29.3), CA (120.0 +/- 32.2), and OA (105.8 +/-
      64.1) groups (p = NS). There was no statistically significance difference in
      length of stay (days) between the LA (9.2 +/- 4.1), OA (10.5 +/- 3.3), and CA
      (10.0 +/- 1.8) groups. The wound infection rate was less frequent in the LA group
      (0%) than in 0A (14%) and CA (10%) groups. The rate of intra-abdominal abscess
      infections (IAAs) and ileus were 22% and 28%, respectively, in LA group, 38% and
      29%, respectively, in OA group, and 60% and 50%, respectively, in CA group.
      CONCLUSIONS: No difference in the rate of postoperative intra-abdominal abscesses
      exists between laparoscopic and open appendectomy for perforated appendicitis.
      Wound infections and ileus complicate the postoperative course of patients after
      laparoscopic appendectomy less frequently than after open appendectomy. The
      conversion of laparoscopic to open appendectomy for perforated appendicitis is
      associated with increased postoperative morbidity.

PMID- 11591964
TI  - Risk factors and the prevalence of trocar site herniation after laparoscopic
      fundoplication.
AB  - BACKGROUND: Although there have been case reports describing trocar site
      herniation after laparoscopic fundoplication, its overall prevalence and the risk
      factors for its development are unclear. METHODS: The records of 320 patients
      undergoing primary laparoscopic fundoplication as treatment for gastroesophageal
      reflex disease (GERD) or hiatal hernia between 1991 and 1999 were reviewed
      retrospectively. Placement of the initial supraumbilical trocar was by the open
      Hassan technique in all patients. RESULTS: Nine patients (five male) with a mean
      age 54 years (range, 37-75) developed trocar site herniation, for an overall
      prevalence of 3%. The mean interval between surgery and diagnosis was 12 months
      (range, 4-21). In all patients, the hernia occurred at the supraumbilical camera
      port site. Patients with trocar hernias tended to have a higher body mass index
      (BMI) than those without hernias (mean BMI, 29.4 kg/m2 vs 27.2 kg/m2, p = 0.13).
      None of the patients developed intestinal obstruction as a consequence of
      herniation. To date, all but one of the hernias have been repaired. Six of them
      required the insertion of a prosthetic mesh. CONCLUSIONS: The prevalence of
      trocar site herniation after laparoscopic fundoplication was minimal at 3%. All
      hernias occurred at the midline supraumbilical port, the only site where open
      trocar insertion was employed. As a consequence of these observations, we have
      developed a new method of open trocar placement. This method utilizes a
      paramedian skin incision and separate fascial incisions through anterior and
      posterior rectus sheathes, with retraction of the rectus abdominis muscle
      laterally.

PMID- 11591965
TI  - Influence of handle design on the surgeon's upper limb movements, muscle
      recruitment, and fatigue during endoscopic suturing.
AB  - BACKGROUND: Thus far, little has been done to investigate the kinematics (motion
      analysis) and kinetics (muscle work, muscle fatigue, comfort) of surgeons during
      laparoscopic surgery. Therefore, we set out to study these ergonomic aspects of
      task performance in the dominant upper limb of surgeons during endoscopic
      suturing. METHODS: Three different handles - conventional finger loop, rocker,
      and ball handle prototype - were compared in a study involving 10 surgeons
      suturing porcine enterotomies with each of the three instruments. The endpoints
      were performance parameters, motion analysis and muscle work, and fatigue of the
      surgeon's dominant upper limb; subjective scores for comfort level and
      maneuverability were also elicited from the subjects. RESULTS: Task quality and
      efficiency during endoscopic suturing, were significantly better with the ball
      and rocker handle needle drivers than with the finger loop instrument, with lower
      angular velocity at the elbow and shoulder joints, more pronation, and less
      supination. The integrated muscle work was much lower for both the rocker and the
      ball handles. Significant muscle fatigue, especially of the arm flexors and
      deltoid, was observed only with finger loop instruments. Comfort and
      maneuverability rating scores were higher with both handles than with the
      conventional finger loop. The ball handle was easier to maneuver, but it was
      somewhat less comfortable than the rocker system. CONCLUSION: A different pattern
      of joint movements, a reduction in muscle power exerted during endoscopic
      suturing, and hence an absence of muscle fatigue were documented with ergonomic
      needle drivers (rocker and ball) when compared to the conventional finger loop
      instruments. These differences translate to better and more efficient task
      performance with enhanced comfort.

PMID- 11591966
TI  - Reliability of the Dundee Endoscopic Psychomotor Tester (DEPT) for dominant hand
      performance.
AB  - BACKGROUND: The Dundee Endoscopic Psychomotor Tester (DEPT) was developed as a
      means of obtaining an objective assessment of endoscopic performance using a
      single hand. This paper evaluates the reliability of the system. METHODS: Twenty
      medical students were tested on the DEPT for four runs using the dominant hand.
      Test-retest reproducibility and coefficient alpha to measure the internal
      consistency were used as indexes of the reliability of the DEPT system. RESULTS:
      A positive correlation was found between different runs in all outcome measures
      of the DEPT. Coefficient a was > 0.7 for all parameters. CONCLUSION: DEPT
      provides a reliable method for the objective assessment of single-handed
      endoscopic performance in terms of aiming and force exerted on the target plate.

PMID- 11591967
TI  - Laparoscopic assisted percutaneous drainage of infected pancreatic necrosis.
AB  - BACKGROUND: Percutaneous drainage of infected pancreatic fluid collections is
      often unsuccessful. Alternatively, open necrosectomy techniques are very morbid.
      We hypothesized that in selected cases, laparoscopic techniques could be used to
      facilitate percutaneous drainage of the residual particulate necrosectum and
      avoid a laparotomy. We report our experience with laparoscopic assisted
      retroperitoneal debridement as an adjunct to percutaneous drainage for patients
      with infected pancreatic necrosis. METHODS: Case studies were reviewed
      retrospectively. We analyzed the course of six patients undergoing laparoscopic
      assisted debridement of infected pancreatic necrosis after failure of
      percutaneous drainage. With the drains and computed tomography (CT) scan used as
      a guide, laparoscopic debridement of the necrosectum was performed. RESULTS:
      Between November 1995 and December 1999, six patients were treated with this
      method. In four patients, laparoscopic assisted percutaneous drainage was
      successful. Two patients required open laparotomy. Complications included a self
      limited enterocutaneous fistula and a small flank hernia. No deaths occurred.
      CONCLUSIONS: This early, limited experience has demonstrated the feasibility of
      laparoscopic assisted percutaneous drainage for infected pancreatic necrosis.
      With this technique, two-thirds of our patients avoided the morbidity of a
      laparotomy.

PMID- 11591968
TI  - Laparoscopic cardiomyotomy and anterior partial fundoplication for achalasia.
AB  - BACKGROUND: Although surgical myotomy is considered the gold standard, many
      different treatments have been advocated for achalasia. There are now a number of
      reports of cardiomyotomy being performed laparoscopically. METHODS: This is a
      prospective study of 82 patients (47 male and 35 female; median age, 47 years)
      who underwent laparoscopic cardiomyotomy and anterior partial fundoplication for
      achalasia. RESULTS: Four of the 82 procedures required conversion to open
      surgery, all during the early stages of the series, and two required early
      reoperation for a postoperative problem. The median operating time was 80 min
      (range, 32-210). the median hospital stay was 3 days (range, 2-18), and normal
      physical activity was resumed after a median of 2 weeks (range, 3 days to 12
      weeks). Follow-up ranged up to 8 years (median, 2). Postoperatively, symptoms of
      dysphagia (to both solids and liquids), heartburn, odynophagia, chest pain,
      regurgitation, and cough were significantly reduced in all patients. The median
      overall satisfaction score (graded from 0 to 10, with 10 representing total
      satisfaction) was 9 (range, 0-10), and 90% of patients were highly satisfied with
      the surgical outcome. CONCLUSION: Laparoscopic cardiomyotomy with anterior
      partial fundoplication achieves excellent symptomatic relief for patients with
      achalasia, and it can be performed with minimal morbidity.

PMID- 11591970
TI  - Outcomes of laparoscopic fundoplication for gastroesophageal reflux disease and
      paraesophageal hernia.
AB  - BACKGROUND: Laparoscopic fundoplication has become the standard for operative
      treatment of gastroesophageal reflux disease (GERD). METHODS: We reviewed our
      experience with 1,000 consecutive patients receiving laparoscopic fundoplication
      for GERD (n = 882) or paraesophageal hernia (n = 118) between October 1991 and
      July 1999. Patients with achalasia and failed fundoplication were excluded from
      analysis. All the patients were evaluated preoperatively by upper endoscopy,
      esophageal manometry, and barium swallow. After 1994, 24-h pH monitoring was
      performed selectively in patients with extraesophageal symptoms and/or those
      without erosive esophagitis. There were 490 men 510 women in this review. Their
      mean age was 49 years. Procedures performed were 360 degrees floppy
      fundoplication (n = 879), 360 degrees fundoplication without fundus mobilization
      (Rossetti) (n = 22), 270 degrees posterior fundoplication (n = 96), and anterior
      fundoplication (n = 2). Esophageal lengthening procedure (Collis gastroplasty)
      was performed in combination with fundoplication in 15 patients. In seven
      patients the treatment was converted to open fundoplication. OUTCOMES: The
      average length of hospitalization was 2.2 days, and 136 patients stayed longer
      than 2 days. Major complications occurred in 21 patients: esophageal perforation
      (n= 10), acute paraesophageal herniation (n = 4), splenic bleeding (n = 2),
      cardiac arrest (n = 1), pneumonia (n = 3), and testicular abscess (n = 1).
      Additional operations were required to manage the complications in 14 patients
      (70%): Four of these procedures were performed emergently, and 10 patients
      underwent reoperation between 6 h and 10 days. There were three deaths, all of
      which involved elderly patients with paraesophageal hernia. There were 35 late
      failures requiring reoperation for recurrence of GERD or development of new
      symptoms: The treatment of 32 patients was revised laparoscopically, and 4
      patients required laparotomy. Beyond 1 year (median follow-up period, 27 months),
      94% of the reviewed patients were satisfied with their surgical outcome.

PMID- 11591969
TI  - Laparoscopic Heller myotomy relieves dysphagia in patients with achalasia and low
      LES pressure following pneumatic dilatation.
AB  - BACKGROUND: Although pneumatic dilatation is said to relieve dysphagia in
      achalasia if it decreases lower esophageal sphincter (LES) pressure to 10 mmHg (n
      = 23); group C, no previous balloon dilatation and LES pressure >10 mmHg (n =
      25). All patients underwent a laparoscopic Heller myotomy and Dor fundoplication.
      The severity of dysphagia was gauged on a scale of 0-4. RESULTS: In group A, LES
      pressure was 7 +/- 2 mmHg preoperatively and 8 +/- 3 mmHg postoperatively; the
      dysphagia score was 3.3 +/- 0.7 preoperatively and 0.9 +/- 1.1 postoperatively.
      Eighty-nine percent of patients had excellent or good results. In group B, LES
      pressure was 23 +/- 8 mmHg preoperatively and 10 +/- 1 mmHg postoperatively; the
      dysphagia score was 3.3 +/- 0.7 preoperatively and 0.3 +/- 0.5 postoperatively.
      All patients had excellent or good results. In group C, LES pressure was 23 +/-
      11 mmHg preoperatively and 14 +/- 12 mmHg postoperatively; the dysphagia score
      was 3.6 +/- 0.6 preoperatively and 0.2 +/- 0.5 postoperatively. All patients had
      excellent or good results. CONCLUSIONS: These results show that (a) a LES
      pressure of <10 mmHg after pneumatic dilatation does not guarantee relief of
      dysphagia, and (b) laparoscopic Heller myotomy relieves dysphagia in most
      patients with a postdilatation LES pressure <10 mmHg. Thus, a laparoscopic Heller
      myotomy is indicated if dilatation does not relieve dysphagia, even if LES
      pressure has been decreased to <10 mmHg. Esophagectomy should be reserved for the
      occasional failure of this simpler operation.

PMID- 11591971
TI  - Outcomes analysis of laparoscopic cholecystectomy in the extremely elderly.
AB  - BACKGROUND: A study was conducted to determine whether extremely elderly
      patients, age 80 years or older, were at higher risk for adverse outcomes from
      laparoscopic cholecystectomy than patients younger than 80 years. METHODS:
      Laparoscopic cholecystectomy was attempted in 421 patients age 65 years or older
      from 1989 through 1999. The patients were divided into two groups: group 1 (age
      65-79 years; n = 351) and group 2 (age, 80-95 years; n = 70). A prospective
      database was analyzed for mean +/- standard deviation and using Student's t-test
      and chi-square analysis. RESULTS: Advanced age (group 2) was associated with a
      higher mean American Society of Anesthesiology (ASA) class (2.7 vs 2.3; p <
      0.001) and a greater incidence of common bile duct stones (43% vs 26%; p < 0.01),
      as compared with those of younger age (group 1). Mean operative times in group 2
      were 106 +/- 45 min as compared with 96 +/- 38 min in group 1, a difference that
      is not significant. The extremely elderly (group 2) had a four-fold higher rate
      of conversion to open cholecystectomy (16% vs 4%) and a longer mean postoperative
      hospital stay (2.1 vs 1.4 days). Grades 1 and 2 complications also were more
      common in group 2: grade 1: group 1, 8.8% vs group 2, 17% and grade 2: group 1,
      4.3% vs group 2, 7.1% (p < 0.05). One patient in group 1 had a myocardial
      infarction 13 days postoperatively, and two deaths occurred in the extremely
      elderly group within 30 days postoperatively. CONCLUSIONS: Laparoscopic
      cholecystectomy in the extremely elderly is associated with more complications
      and a higher rate of conversion to open cholecystectomy than in elderly
      individuals younger than 80 years. The greater chance of encountering a severely
      inflamed or scarred gallbladder and common bile duct stones as well as increasing
      comorbidities likely account for these differences in outcome.

PMID- 11591972
TI  - Long-term follow-up of thoracoscopic splanchnicectomy for chronic pancreatitis
      pain.
AB  - BACKGROUND: Thoracoscopic splanchnicectomy (SPL) has been reported to give
      excellent short-term pain relief in chronic pancreatitis. This study
      prospectively evaluates the long-term efficacy of SPL in pancreatitis patients.
      METHODS: Chronic pancreatitis patients with severe pain unrelieved by standard
      therapy completed a standard 10-point analogue pain scale prior to surgery and at
      postoperative visits. Midline and left-sided pain was treated with left SPL;
      right-sided pain was treated with right SPL. If pain recurred on the
      contralateral side, contralateral SPL was done. RESULTS: Fifteen patients
      underwent SPL. Eleven of them required narcotics preoperatively. Follow-up is
      complete and ranges from 4.2 to 6.1 years (median, 5.75). All patients had
      constant pain prior to surgery. Following SPL, it decreased in the short term to
      a mean of 3.9 attacks a month. At long-term follow-up, the mean number of attacks
      was 8.6 per month. Preoperatively, the mean score for worst pain within the last
      2 months was 9.1. This score decreased to 3.9, but at long-term follow-up it had
      increased to near preoperative values (8.6). Current severity of pain decreased
      from 7.2 preoperatively to 2.9 at short-term follow-up, but at long-term follow
      up it had increased. The degree of disability decreased from 9.1 preoperatively
      to 5.1 at short-term follow-up, but in the long term it increased toward
      preoperative values. Although eight patients were narcotic free at early follow
      up, only three remained narcotic free in the long-term. CONCLUSION: Thoracoscopic
      SPL offers short-term relief of pain from chronic pancreatitis, but the relief is
      not durable in most cases. Similarly, there are short-term improvements in degree
      of disability, mood, and freedom from narcotic use that are not sustained in the
      long-term. Nevertheless, two-thirds of patients stated that they would have the
      surgery again.

PMID- 11591973
TI  - Effects of helium pneumoperitoneum in pregnant ewes.
AB  - BACKGROUND: Previous animal studies have demonstrated that a carbon dioxide
      (CO(2)) pneumoperitoneum in pregnant ewes causes maternal and fetal acidosis,
      decreased uterine blood flow (UtBF), and fetal hypertension. This study was
      undertaken to determine whether helium (He) produces these same effects when used
      as an insufflating gas. METHODS: Six gravid ewes, at 116 to 120 days gestation,
      underwent catheterization of the maternal femoral artery and vein and the fetal
      hindlimb artery and vein, as well as insertion of a uterine artery flow probe.
      After a 6-day recovery period, the animals were anesthetized; a Hasson trocar was
      placed; and an He pneumoperitoneum was established (10 mmHg for 30 min followed
      by 15 mmHg for 30 min). The following parameters were recorded at baseline and at
      preset time points: maternal and fetal heart rate (HR), blood pressure (BP),
      arterial blood gasses, maternal end-tidal CO(2) (EtCO2), and UtBF. The percentage
      of change over time was determined for each variable. The results were compared
      with results previously obtained in control animals and in animals undergoing
      CO(2) pneumoperitoneum. Statistical significance was determined by repeated
      measures analysis of variance (ANOVA). RESULTS: The following statistically
      significant changes were found. CONCLUSIONS: Like CO(2), He used for
      pneumoperitoneum resulted in decreased UtBF and fetal hypertension because of
      increased intra-abdominal pressure. Unlike a CO(2), He used for pneumoperitoneum
      does not cause maternal or fetal acidosis, indicating that the metabolic effects
      seen with CO(2) are the result of the specific gas used. Therefore, He may be a
      safer gas than CO(2) to use for laparoscopic procedures in pregnant patients.

PMID- 11591975
TI  - Video-assisted resection of pulsative midesophagus diverticula.
AB  - BACKGROUND: Pulsative diverticula located in the midesophagus occur rarely.
      Surgical treatment is indicated for symptomatic diverticula. This study evaluated
      a new minimally invasive method of treatment. METHODS: Three women, ages 69 to 73
      years, underwent resections of diverticula via a thoracoscopic access. No major
      complications were observed. Preoperative symptoms such as dysphagia,
      regurgitation, aspiration, loss of weight, and retrosternal pain were not
      reported at follow-up assessment 3 to 60 months after surgery. The patients were
      highly satisfied with the functional results. CONCLUSIONS: According to our
      results, minimally invasive treatment of midesophagus diverticula by
      thoracoscopic resections may be performed with excellent outcome.

PMID- 11591974
TI  - Lymphatic mapping improves staging during laparoscopic colectomy for cancer.
AB  - BACKGROUND: Recently, lymphatic mapping (LM) of the sentinel lymph node (SN) has
      been coupled with ultrastaging methods to diagnose nodal micrometastases from
      colorectal cancer (CRC). We have developed a technique for LM at the time of
      laparoscopic colon resection (LCR). METHODS: Between August 1996 and February
      2000, 11 patients with small early-stage CRC underwent laparoscopic LM and LCR.
      The primary tumor/polyp site was visualized through a colonoscope and either
      tattooed preoperatively with a carbon dye (India ink), or stained
      intraoperatively by peritumoral injection of isosulfan blue dye. Immediately
      after intraoperative injection of blue dye, efferent lymphatic channels were
      visualized through the laparoscope and followed to the SN. Each blue-stained SN
      was marked with a suture or clip. RESULTS: In all 11 cases, laparoscopic LM
      identified between one and three SN draining the primary tumor. LM added ~15-20
      min to the operating time. The SN correctly reflected the nodal status of the
      entire specimen in all cases. In the one node-positive case, micrometastases were
      found only in an SN and only after cytokeratin immunohistochemistry (CK-IHC). In
      four cases, LM demonstrated unexpected primary lymphatic drainage that prompted
      an increase in the margins of resection. CONCLUSIONS: LM during laparoscopic
      colectomy for CRC may be useful to mark the primary tumor site and to demonstrate
      lymphatic drainage that can alter the margins of resection. Focused examination
      of SN identifies occult micrometastases that up-stage CRC.

PMID- 11591976
TI  - Association between laparoscopic abdominal surgery and postoperative symptoms of
      raised intracranial pressure.
AB  - Animal models have illustrated that a carbon dioxide (CO(2)) pneumoperitoneum can
      cause a rise in intracranial pressure (ICP). This study investigated key symptoms
      and signs of raised ICP in 39 patients after laparoscopic abdominal surgery and
      compared them with a control group of 33 patients after open operations. The
      findings show that the incidence of headache and nausea was significantly higher
      in the laparoscopic group than in the control subjects. End-tidal CO(2) levels
      were recorded, and no significant difference was found between patients and
      control subjects. We conclude that these results could be explained by raised
      intracranial pressure exacerbated by the CO(2) pneumoperitoneum, and that this
      effect is not mediated by raised expiratory CO(2) levels intraoperatively.

PMID- 11591977
TI  - Study comparing sutures and nonpenetrating titanium clips for arteriotomy closure
      after embolectomy.
AB  - BACKGROUND: The vascular closure staple (VCS) clip applier system is an
      alternative to suture for closing arteriotomies and performing vascular
      anastomoses. This study was designed to evaluate the possible advantages of its
      use in closing arteriotomies after embolectomy. METHODS: In this study, 26
      patients with upper or lower extremity embolism underwent embolectomy, and the
      arteriotomy was closed using either VCS clips (group A) or sutures (group B).
      RESULTS: The time required for arteriotomy closure with clips (11.2 +/- 2.7s) was
      considerably shorter than the time required with sutures (241.2 +/- 48.7s; p <
      0.0001), resulting also in shorter clamp times (380.8 +/- 127.3s vs 612.7 +/-
      112.6 s; p < 0.0001). No hemodynamically significant stenoses or pseudoaneurysms
      were detected at the arteriotomy sites in any of the patients up to 1 year after
      embolectomy. CONCLUSIONS: The VCS clip applier system, a quick and easy method
      for closing arteriotomies, is as safe as sutures in terms of narrowing of the
      artery and formation of pseudoaneurysm.

PMID- 11591978
TI  - Elevated intrahepatic pressures and decreased hepatic tissue blood flow prevent
      gas embolus during limited laparoscopic liver resections.
AB  - BACKGROUND: As new techniques are emerging for laparoscopic liver resections,
      concerns have been raised about the development of gas embolus related to the
      CO(2) pneumoperitoneum. We hypothesized that elevated intrahepatic vascular
      pressures and decreased hepatic tissue blood flow (LQB) would prevent gas embolus
      during laparoscopic liver resections under conventional pneumoperitoneum.
      METHODS: Intrahepatic vascular pressures and LQB were measured in nine pigs with
      varying CO(2) pneumoperitoneum. Gas embolus was determined after hepatic incision
      by monitoring pulmonary arterial pressure (PAP), hepatic venous PCO(2), systemic
      blood pressure (SBP), and suprahepatic vena cava ultrasound. RESULTS: As the
      pneumoperitoneum was increased from 0 to 15 mmHg, intrahepatic vascular pressures
      increased significantly (p < 0.05), while LQB decreased significantly (p < 0.05).
      A 2.0-cm hepatic incision at 4, 8, 15, and 20mmHg produced no ultrasound evidence
      of gas embolus and no changes in PAP, SBP, or hepatic venous PCO(2) (p = NS).
      CONCLUSION: These data suggest that the risk of significant embolus under
      conventional pneumoperitoneum is minimal during laparoscopic liver resections.

PMID- 11591979
TI  - The role of video-assisted thoracoscopic surgery in the diagnosis of the small
      peripheral pulmonary nodule.
AB  - BACKGROUND: The use of imaging techniques to detect small peripheral pulmonary
      nodules often results in a missed diagnosis. Thoracoscopy had limited application
      until recently, when advances in technology allowed thoracic surgeons greater
      visualization and mobility within the chest. METHODS: Between September 1992 and
      June 1997, 81 patients were treated for small peripheral pulmonary nodules by
      pulmonary wedge excision using video-assisted thoracoscopic techniques. The
      patients were 39 men and 42 women with an average age of 59.5 years. RESULTS: A
      definitive diagnosis was obtained in all cases. Malignancies were found in 44
      patients (55%), which involved primary lung cancer in 28 patients and metastatic
      lesions in 16 patients. The rate of malignancy in nodules measuring 1 cm or less
      was 18%. There was no operative mortality or morbidity. CONCLUSIONS: We conclude
      that video-assisted thoracoscopic lung biopsy is a more effective and less
      invasive diagnostic tool for small peripheral pulmonary nodules.

PMID- 11591980
TI  - Early clinical outcomes after subfascial endoscopic perforator surgery (SEPS) and
      saphenous vein surgery in chronic venous insufficiency.
AB  - BACKGROUND: Subfascial endoscopic perforator surgery (SEPS) has recently become
      popular as a minimally invasive way to treat chronic venous insufficiency (CVI)
      of the lower extremities. We report the early clinical outcomes of SEPS and
      saphenous vein surgery in a prospective series of Chinese patients who presented
      with severe CVI. METHODS: All patients referred to our hospital for the
      management of severe CVI (class IV disease or above) after January 1998 underwent
      SEPS using an ultrasonic scalpel in conjunction with saphenous vein surgery. All
      patients were followed up prospectively to assess ulcer healing, ulcer
      recurrence, and symptoms after SEPS. Clinical outcome was evaluated by the
      scoring system suggested by the Consensus Committee of the American Venous Forum
      on Chronic Venous Disease. RESULTS: Over a 24-month period, we performed 36 SEPS
      on 31 patients. Nineteen lower extremities (53%) had active or healing ulcers.
      Sapheno-femoral ligation was also performed in 33 limbs (92%). Four limbs (11%)
      developed superficial wound infection, and two (6%) had saphenous nerve
      dysesthesia. The mean clinical score and disability score decreased from 8.42 to
      3.42 and 1.45 to 0.31 respectively, after a median follow-up of 14 months (range,
      6-22) (p < 0.005). Eleven ulcers (58%) healed within 6 weeks after surgery. At 1
      year follow-up, ulcer recurrence was found in two legs (11%). CONCLUSION: SEPS is
      safe and feasible. Early clinical results have shown a promising outcome in
      patients with severe chronic venous insufficiency.

PMID- 11591981
TI  - Gasless laparoscopy could avoid alterations in hepatic function.
AB  - BACKGROUND: In a previous clinical study, we showed that the duration and level
      of pneumoperitoneum are responsible for changes in hepatic function during
      laparoscopic procedures. These findings encouraged us to evaluate hepatic
      function during laparoscopy with and without carbon dioxide (CO(2))
      pneumoperitoneum in a clinical setting. METHODS: We performed 63 laparoscopic
      cholecystectomies and 30 non-hepatobiliary laparoscopic procedures in 93
      consecutive patients with normal preoperative liver function tests. The
      anesthesiologic protocol was uniform, using drugs at low hepatic metabolism. We
      performed laparoscopic cholecystectomies in 43 patients with a pneumoperitoneum;
      in the remaining 20, we used a gasless technique. We randomized the 43
      laparoscopic cholecystectomies into 23 performed with pneumoperitoneum at 14 mmHg
      and 20 performed at 10 mmHg. All non-hepatobiliary laparoscopic procedures were
      performed with a pneumoperitoneum of 14 mmHg. The postoperative serologic levels
      of AST, ALT, and bilirubin, and the prothrombin time were measured at 6, 24, 48,
      and 72 h. The alterations in the serologic hepatic tests were then related to the
      type of procedure, its duration, and the level of pneumoperitoneum. RESULTS: The
      study group was comprised of 93 patients, 39 male and 54 female, with a mean age
      of 50.5 years (range, 15-74). There were no deaths. There was no morbidity in the
      pneumoperitoneum group, but there was one case of accidental omental injury
      during the placement of the abdominal, wall retractor in the gasless group. All
      patients had postoperative changes in serologic hepatic tests. Slow return to
      normality occurred 48 or 72 h after the operation. The increase in AST and ALT
      was statistically significant and correlated to the level and duration of
      pneumoperitoneum. The serologic change in the gasless group were significantly
      lower than in the laparoscopic cholecystectomy group with pneumoperitoneum at 14
      mmHg. There was no statistically significant difference between the gasless group
      and the laparoscopic cholecystectomy group with pneumoperitoneum at 10 mmHg.
      There was a statistically the significant increase in the non-hepatobiliary
      laparoscopy group over the gasless group, despite the absence of hepatobiliary
      injuries in the first group. No symptoms were related to these serologic hepatic
      changes. CONCLUSIONS: The gasless technique causes smaller alterations in
      serological hepatic parameters than pneumoperitoneum at 14 mmHg. By contrast, the
      gasless technique and low-pressure pneumoperitoneum have the same effect on
      hepatic function. Therefore, the use of a subcutaneous abdominal wall retractor
      combined with a low-pressure pneumoperitoneum is recommended for patients with
      severe hepatic failure. Transaminases

PMID- 11591983
TI  - Surgical treatment for abdominal neuroblastoma in the laparoscopic era.
AB  - BACKGROUND: The role of laparoscopy in children with cancer has not been fully
      defined. The aims of this study were to develop an optimal surgical procedure for
      the treatment of abdominal neuroblastoma in the laparoscopic era and to evaluate
      the advantages and disadvantages of laparoscopy in the pediatric population.
      METHODS: Since July 1997, 37 children were diagnosed with abdominal neuroblastoma
      at our center, and 44 surgical procedures were performed on them. Patients with
      advanced neuroblastoma underwent laparoscopic biopsy, open biopsy, and delayed
      primary or second-look excision, whereas early neuroblastoma cases had either
      laparoscopic or open excision. We compared the length of the operation,
      intraoperative blood loss, length of hospital stay, complications, and time to
      start postoperative feeding and chemotherapy for the laparoscopic and open
      surgery groups. RESULTS: Length of stay and time to postoperative feeding and
      chemotherapy were significantly lower in the laparoscopic group than the open
      surgery group. However, there were no significant differences between the two
      groups in length of operation and intraoperative blood loss. CONCLUSION:
      Laparoscopic biopsy and excision of abdominal neuroblastoma are effective and
      efficient surgical procedures in children.

PMID- 11591982
TI  - Laparoscopic partial or cortical-sparing adrenalectomy by dividing the adrenal
      central vein.
AB  - BACKGROUND: We perform laparoscopic partial adrenalectomy without sectioning the
      adrenal central vein has been described because it is important to preserve this
      vein in the remnant adrenal gland in order to maintain its function. In this
      article, we describe our technique for laparoscopic partial or cortical-sparing
      adrenalectomy by dividing the adrenal central vein. METHODS: The procedures were
      performed in four patients with aldosterone-producing adenomas (APA) and two
      patients with pheochromocytomas. RESULTS: There were no postoperative
      complications. At follow-up, adrenal 131I-adosterol scintigrams showed that
      remnant adrenal function had been preserved in all cases. CONCLUSION: Since the
      vascular bed adjacent to the remnant adrenal gland is integral to the
      preservation of its function, it is important to perform procedures that do not
      separate the remnant adrenal gland from the retroperitonium space. Because the
      operative field is clearly visualized on the high-magnification video monitor,
      this delicate procedure can be performed with a high degree of accuracy via the
      laparoscopic approach. We consider this operative technique to be useful for
      selected cases.

PMID- 11591984
TI  - Bilateral internal thoracic artery harvesting under robotic video-assistance.
AB  - BACKGROUND: Following upon the recent development of minimally invasive coronary
      robotic surgery, we set out to evaluate the feasibility of bilateral internal
      mammary artery (IMA) harvesting using the voice-controlled AESOP 2000 video
      assisted robot. METHODS: The robot is placed on the right side of the patient.
      The left IMA is first totally video-harvested, with the arm of the robot crossing
      over the patient to reach the left chest. The voice-controlled movement of the
      arm allows the surgeon to obtain the best video image of the artery. After
      completion of the dissection, the arm is positioned on the right part of the
      chest. The right IMA is then harvested using the same technique. RESULTS: Two
      patients underwent harvest of a bilateral IMA using this technique. The time of
      dissection was 52 min and 86 min, respectively. CONCLUSION: This technique allows
      a more precise, faster, tremor-free dissection, as compared to a conventional
      thoracoscopic harvesting.

PMID- 11591985
TI  - An unusual case of gastric volvulus after laparoscopic paraesophageal hernia
      repair.
AB  - Laparoscopic surgery for paraesophageal hernia is well accepted. However, the
      complications of this relatively new procedure have not been thoroughly
      investigated. Only four cases of recurrent volvulus after paraesophageal hernia
      repair have been reported. A 52-year-old man presented with a large right-side
      paraesophageal hernia. He experienced a retroperitoneal midgastric volvulus
      despite correct orientation of the stomach distally and proximally. We report an
      unusual complication that seems congenital in origin. Diagnostic and corrective
      measures are suggested.

PMID- 11591986
TI  - Agenesis of the gallbladder associated with Gilbert's syndrome.
AB  - A case of gallbladder agenesis associated with Gilbert's syndrome in a 52-year
      old man with a striking family history of cholelithiasis is reported. The
      diagnosis of Gilbert's syndrome was made 30 years earlier, whereas the anomaly of
      the gallbladder was manifested when the patient, at the age of 34 years, started
      complaining of abdominal symptoms suggestive of biliary tract disease. Diagnostic
      confirmation was accomplished by magnetic resonance cholangiography, thus
      avoiding laparotomy, whereas conventional hepatobiliary imaging studies and
      laparoscopy could not achieve a definite diagnosis. No other malformations were
      detected. To our knowledge, this is the first report of an association between
      gallbladder agenesis and Gilbert's syndrome. Such association may be incidental
      or could represent the occurrence of a concomitant metabolic error in adults with
      isolated agenesis of the gallbladder.

PMID- 11591987
TI  - Gallbladder injury in blunt abdominal trauma.
AB  - A 36-year-old woman was admitted to the hospital for an abdominal blunt trauma.
      At ultrasound (US) and computed tomography (CT), a gallbladder lesion was
      suspected, along with a tear of the liver. The patient was submitted to a
      diagnostic laparoscopy. The gallbladder was partially avulsed and bile was
      infiltrated in the hepatoduodenal ligament. Intraoperative cholangiography and
      Kocher's maneuver excluded other lesions. Laparoscopic cholecystectomy was
      performed, but due to severe hemorrhage from the liver tear, the operation was
      converted to an open procedure. Gallbladder lesions in blunt trauma are rare
      occurrences, but they are often associated with other organ injuries. US and CT
      scan are valuable for their diagnosis, but if a lesion is suspected, diagnostic
      laparoscopy is advisable in stable patients. It should be accompanied by a cystic
      duct cholangiography and a Kocher's maneuver to evaluate the integrity of the
      biliary tree. Laparoscopic cholecystectomy is generally feasible. Associated
      lesions require laparotomy when they are not amenable to laparoscopic treatment.

PMID- 11591988
TI  - Abdominal ultrasonography reveals the perforation site of duodenal ulcers.
AB  - Regardless of whether or not the laparoscopic approach is used, the simple
      closure using an omental patch is considered to be preferable to other surgical
      therapies for a duodenal ulcer perforation. We used abdominal ultrasonography
      (US) to identify the perforation site of the duodenal ulcer. To our knowledge,
      this is the first report describing how the perforation site of duodenal ulcers
      can be identified using US. Three patients diagnosed with perforated duodenal
      ulcers based on abdominal computed tomography and abdominal radiographic findings
      were scheduled for surgery. Under general anesthesia, US demonstrated free air on
      the liver and a "fish-eye sign" when the anterior or lateral wall was perforated.
      We performed a simple closure using an omental patch through a skin incision
      measuring only 3 cm in diameter above the area showing the fish-eye sign. The
      postoperative recovery was no different from that seen when a laparoscopic
      approach is used at our hospital. Even though the laparoscopic procedure is still
      the surgical modality of choice, the US technique allows for a successful
      diagnosis without invasive examinations. We believe that most surgeons and/or
      radiologists should try to detect the fish-eye sign using US as the diagnostic
      modality of first choice if they suspect a duodenal ulcer perforation. This
      technique allows us to mark the perforation site accurately before surgery.

PMID- 11591989
TI  - Laparoscopic fenestration and modified marsupialization of posttraumatic splenic
      cysts using a harmonic scalpel.
AB  - In recent years, the advanced laparoscopic experience has revolutionized surgery
      and fostered the expansion of the indications for minimally invasive surgery in
      the diagnosis and treatment of all intra-abdominal pathology. Total splenectomy,
      which traditionally was the procedure of choice in the treatment of symptomatic
      nonparasitic splenic cysts, recently has been changed to a more conservative
      approach by many authors [1, 5, 9]. The conservative methods preserve immunologic
      function of the spleen and prevent the potentially fatal postsplenectomy sepsis
      complications [9]. We successfully performed laparoscopic fenestration and
      modified marsupialization of these cysts using a harmonic scalpel on two patients
      with symptomatic splenic psuedocysts.

PMID- 11591990
TI  - Treatment of postoperative bronchobiliary fistula by nasobiliary drainage.
AB  - Bronchobiliary fistula (BBF) is a rare condition. It may present as a
      complication of echinococcal or amebic liver disease. Management of such a
      fistula can be very difficult and is often associated with a high rate of
      morbidity and mortality. We report the case of a 70-year-old woman who presented
      with a BBF after a one-stage operation for hydatid cysts of the liver and lung
      that were approached via thoracotomy and transdiaphragmatic incision. The cause
      of the BBF was an inflammatory collection in the residual liver cavity due to
      inadequate drainage. This collection eroded the sutured diaphragm, and because of
      the existing adhesions, it perforated directly into the bronchial system at the
      area of the previous cystectomy. Initially, endoscopic sphincterotomy was
      performed to achieve biliary decompression by equalizing intrabiliary and
      duodenal pressure, but no significant improvement was seen. Subsequently,
      nasobiliary drainage was instituted by means of an endoscopically inserted,
      nasobiliary catheter, which further reduced biliary pressure and facilitated
      biliary flow to the duodenum, as opposed to the fistulous tract. The fistula was
      successfully closed in a short time. This conservative method reduces the risks
      of reoperation. Therefore, it should be considered the treatment of choice in the
      management of bronchobiliary fistula.

PMID- 11591991
TI  - Laparoscopic distal pancreatectomy for blunt injury to the pancreas. A case
      report.
AB  - Laparoscopic pancreatic resection has not been reported for traumatic injuries to
      the pancreas. We present the case of a laparoscopic distal pancreatectomy
      performed on a 10-year-old boy after he sustained a distal transection of the
      pancreas due to blunt abdominal trauma. The spleen and its vessels were
      preserved. The patient was sent home on postoperative day 3 without any
      postoperative complications. Performing an advanced laparoscopic pancreatic
      procedure is feasible, in the trauma setting, particularly in children.

PMID- 11591992
TI  - Laparoscopy of a traumatic rupture of a dysontogenetic splenic cyst. A case
      report.
AB  - The role of laparoscopy in the stepped approach to the diagnosis and treatment of
      blunt abdominal trauma has not yet been fully elucidated. Despite the use of a
      variety of imaging modalities, it can still be difficult to make a proper
      evaluation in cases where there are questionable abdominal injuries. In
      particular, when there is a discrepancy between a bland clinical picture and the
      results of diagnostic imaging procedures, laparoscopy should be given preference
      over laparotomy, provided the patient's circulatory situation is stable. Herein
      we describe a case in which laparoscopy allowed the detection and treatment of a
      traumatic rupture of a dysontogenetic splenic cyst that had mimicked a rupture of
      the spleen on both the ultrasound (US) and computed tomography (CT) images.

PMID- 11591993
TI  - Videoendoscopic surgery combined with a minimal sternotomy for removing a thyroid
      tumor extending into the mediastinum. A case report.
AB  - We report the case of a 55-year-old man with a giant goiter descending to the
      mediastinum. Video-endoscopic surgery combined with a minimal sternotomy was
      performed to remove a thyroid tumor. In the course of our dissection of the
      subplatysmal space, an endoscopic approach was applied to avoid incisions of the
      neck. Three trocars were inserted from the anterior chest wall, and carbon
      dioxide (CO2) was insufflated at a pressure of 5 mmHg to create a working space.
      This technique improves the cosmesis of thyroidectomies and cervical operations.

PMID- 11591994
TI  - Mediastinal pancreatic pseudocyst in a child. A thoracoscopic approach.
AB  - Mediastinal pancreatic pseudocyst is a rare occurrence in children and may be
      difficult to diagnose. Internal drainage via a cystenterostomy and a simple
      external drainage are two of the treatment options that are currently employed.
      We describe the case of an 11-year-old boy with a mediastinal pseudocyst who was
      treated via a thoracoscopic approach using an original pulmonary exclusion. The
      pseudocyst disappeared in 15 days and there has been no recurrence. No adjuvant
      treatment was necessary. Endoscopic retrograde cholangiopancreatography (ERCP)
      was useful in establishing the etiology (pancreas divisum). We believe that the
      thoracoscopic approach is a reproducible, simple, and safe procedure for the
      treatment of mediastinal pseudocysts. The technique may represent a valid
      alternative to cystogastrostomy.

PMID- 11591995
TI  - Bladder injury during diagnostic laparoscopy. A case report.
AB  - We report the case of a bladder injury that was incurred during diagnostic
      laparoscopy in a 19-year-old man with hepatomegaly, neuropsychiatric
      disturbances, and urinary retention whose final diagnosis was Wilson's disease.
      In order to define the nature of his hepatomegaly, the patient underwent
      laparoscopy. However, the lack of recognition of urinary retention by the
      operator and the absence of cooperation by the patient caused bladder injury
      during the insertion of the Veress needle, resulting in the leakage of a yellow
      fluid consistent with urine. Since the injury was small, it was managed with
      antibiotics and bladder drainage, alone and deemed not to require surgical
      repair. We also discuss potential risk factors and describe some approaches that
      can help to avoid this laparoscopic complication.

PMID- 11591996
TI  - Laparoscopic transabdominal suspension sutures.
AB  - A limited number of access ports used in laparoscopic surgery may impair the
      ability of the surgeon to achieve adequate retraction and exposure, or to
      stabilize "moving targets" while operating on nonfixed organs. Solutions such as
      adding more ports or using a hand-assisted technique have the disadvantages of
      being more invasive, possibly creating a cumbersome situation of multiple
      instruments in a limited working space. We describe a useful technique for
      retraction and stabilization with the use of temporary sutures that pass through
      the abdominal wall. Although not new, this technique is not widely known or used,
      and laparoscopic surgeons may find it useful for a variety of applications.

PMID- 11591997
TI  - Editorial on laparoscopic adjustable gastric banding one-sided.

PMID- 11591999
TI  - Stapled and nonstapled laparoscopic transabdominal preperitoneal inguinal hernia
      repair.

PMID- 11592001
TI  - A critical look at an editorial judgment.

PMID- 11592002
TI  - Perforated subhepatic appendicitis in the laparoscopic era.

PMID- 11592003
TI  - SAGES and surgical education: assuring that history does not repeat itself.

PMID- 11592005
TI  - [Viagra and ophthalmology].

PMID- 11592006
TI  - [Variability of ocular response to drugs].

PMID- 11592007
TI  - [Diode laser contact transscleral cyclophotocoagulation].

PMID- 11592008
TI  - [Analysis of eye disease and adaptation of visual aids in low vision patients:
      review of 1,000 cases].
AB  - PURPOSE: To study the success of visual rehabilitation in a group of 1,000
      patients with low vision. METHOD: Clinical data on visual rehabilitation was
      studied in 1,000 subsequent patients suffering from visual impairment. Study
      focused on ocular disease, improvement in visual acuity and successful use of
      visual aids. A statistical analysis of results is presented. RESULTS: 25 cases
      dropped out due to issues in primary diagnosis. Remaining 975 patients were
      assigned to 9 groups: age-related macular degeneration (339) diabetic retinopathy
      (264 cases), myopic maculopathy (195 cases), glaucoma (96 cases), congenital
      maculopathy (39 cases), retinal detachment (12 patients), retinitis pigmentosa
      (13 cases), macular pucker (6 patients) and a miscellaneous group of 11 cases.
      The overall success in the improvement in visual acuity was 98% except for a
      group of patients with retinitis pigmentosa where a rate of only 46% success
      (p<0.01) was observed. 76% of cases finally accepted visual rehabilitation aids.
      CONCLUSIONS: The usefulness of visual rehabilitation in low vision patients is
      confirmed, with the exception of retinitis pigmentosa cases, probably due to
      features of the disease itself. The design of visual aids should be improved in
      order to benefit a greater number of patients.

PMID- 11592009
TI  - [Comparison of 2 lacrimal punctal occlusion methods].
AB  - PURPOSE: To study and compare two methods for canalicular occlusion: Cautery and
      Punctal Patch. METHOD: The study included fourty patients divided in two groups
      of 20 patients. The end point was 4 occluded puncti. The first group underwent
      deep cauterization resulting in occlusion of the full vertical aspect of the
      canaliculus. The second group underwent punctal patch technique for canalicular
      occlusion. Differential parameters were the following: time of intervention, ease
      of use, risks and precision. In the post operatory, discomfort, subjective and
      objective improvement in ocular surface as well as long term result of each
      technique was analysed. RESULTS: Time of intervention was longer for punctal
      patch compared to cautery. Both methods exhibited similar ease of use and
      improvement in ocular surface. Precision was high in punctal patch technique
      showing complete and final occlusion and no punctum needed reopening, while
      cautery technique presented 20% rate of reopening intervention. Postoperatory
      discomfort and irritation were remarkably evident with punctal technique, while
      minimal in cautery technique. CONCLUSION: Survival analysis after one year follow
      up, showed a higher rate of advantages for punctal patch technique over cautery
      technique.

PMID- 11592011
TI  - [Results in the treatment of acute endophthalmitis by vitrectomy using limbal
      incision].
AB  - PURPOSE: To describe the results obtained in the treatment of acute onset
      endophthalmitis after cataract surgery in our center using vitrectomy with
      corneal limbal incisions. METHODS: Study carried out in 12 patients with acute
      endophthalmitis after cataract surgery in whom a posterior vitrectomy by limbic
      incisions was performed followed by intravitreal injections of antibiotics
      (vancomycin + ceftazidime/amikacin) with systemic and topical antibiotic and
      corticosteroid treatment in the post-operative period. RESULTS: The incidence of
      endophthalmitis in our center was 0.92%. The most frequently isolated
      microorganism was Staphylococcus epidermidis (4 cases, 33.33%). Four cases were
      negative (33.33%). A visual acuity equal to or greater than 0.5 at three months
      was obtained in 6 patients (50%). Only one case required a second administration
      of intravitreal injections. One patient suffered vitreal hemorrhaging in the post
      operative period, and no other complications were observed in the remaining
      patients. CONCLUSIONS: We consider that vitrectomy through limbal incisions is a
      valid alternative for acute onset endophthalmitis treatment.

PMID- 11592010
TI  - [Posterior segment intraocular foreign bodies. Clinical and epidemiological
      features].
AB  - OBJECTIVES: To evaluate the epidemiologic factors, associated ocular involvement
      and visual results in patients with intraocular foreign bodies lodged in the
      posterior segment. METHODS: In this retrospective study, the clinical records of
      21 patients admitted to the hospital with intraocular foreign bodies between
      August 1994 and March 1998 were reviewed and evaluated in regards to age, gender,
      type of injury, foreign body nature, need for surgical intervention,
      complications and final visual acuity. RESULTS: All the patients were males, with
      a mean age of 38.7 years and an average follow-up period of 15.04 months. The
      foreign bodies were caused by work accidents in 2/3 of the cases and 71.4%
      involved ferromagnet metal. Sixteen patients underwent vitrectomy to remove the
      intraocular foreign body. Final visual acuity was equal to or greater than 0.4 in
      57.9% of the patients and there was no light perception in 15.7%. The principal
      late complications were retinal detachment (19.04%), pthisis bulbi (14.2%) and
      cataracts (9.5%). CONCLUSIONS: Most of the intraocular foreign bodies are found
      in young males as a consequence of work accidents. Most patients require
      vitrectomy to remove the foreign body and even though good visual results are
      obtained in many cases, other cases suffer severe visual loss.

PMID- 11592012
TI  - [The Autocad system for planimetric study of the optic disc in glaucoma:
      technique and reproducibility study].
AB  - PURPOSE: To develop a lens planimetry technique for the optic disc using AutoCAD.
      To determine variability magnitude of the optic disc morphological measurements.
      METHODS: We employed AutoCAD R.14.0 Autodesk: image acquisition, contour
      delimitation by multiple lines fitting or ellipse adjustment, image
      sectorialization and measurements quantification (optic disc and excavation,
      vertical diameters, optic disc area, excavation area, neuroretinal sector area
      and Beta atrophy area). Intraimage or operator and interimage o total
      reproducibility was studied by coefficient of variability (CV) (n=10) in normal
      and myopic optic discs. RESULTS: This technique allows to obtain optic disc
      measurement in 5 to 10 minutes time. Total or interimage variability of
      measurements introduced by one observer presents CV range from 1.18-4.42.
      Operator or intraimage measurement presents CV range from 0.30-4.21. Optic disc
      contour delimitation by ellipse adjustment achieved better reproducibility
      results than multiple lines adjustment in all measurements. CONCLUSIONS: Computer
      assisted AutoCAD planimetry is an interactive method to analyse the optic disc,
      feasible to incorporate to clinical practice. Reproducibility results are
      comparable to other analyzers in quantification optic disc morphology. Ellipse
      adjustment improves results in optic disc contours delimitation.

PMID- 11592013
TI  - [Bioadhesives in ocular surgery].
AB  - PURPOSE: To evaluate the histological inflammatory activity that bioadhesives
      such as fibrin, cyanoacrylate, unsutured valved closure and suturing, generate
      when applied on scleral tissue. METHODS: We used a total of 80 eyes of 80 white
      rabbits which we divided into 8 groups of ten eyes each and distributed according
      to the two periods of time (1 week and 30 days) and four technique used for
      closure: 10/0 nylon suture, sutureless self-sealing, cyanoacrylate glue
      (Histoacryl), and fibrin glue (Tissucol). ANOVA was used for the statistical
      study of histological inflammation. Descriptive statistical analysis was used for
      the study of the degree of healing. RESULTS: After 7 days, the fibrin bioadhesive
      led to greater inflammatory response than did the other techniques (p<0.001). The
      cyanoacrylate adhesive caused less inflammatory activity than did suturing
      material (p<0.005). On day 30, the inflammatory reaction generated by the fibrin
      and cyanoacrylate adhesives was greater than of the suturing and self valved
      closure technique (p<0.005). After 7 days, the degree of healing with the suture,
      sutureless technique and cyanoacrylate adhesive was incomplete, while healing was
      moderate with the fibrin glue. After 30 days the degree of healing with
      cyanoacrylate glue was incomplete. At this time the degree of healing, with the
      suture, sutureless technique and fibrin adhesive was complete. CONCLUSIONS:
      Fibrin causes greater inflammatory reaction than do the other techniques. The
      cyanoacrylate adhesive shows a biological tolerance identical to the suture
      technique. This shows that cyanoacrylate bioadhesives are a viable alternative to
      suturing in scleral surgery.

PMID- 11592014
TI  - [Unilateral papilledema in pseudotumor cerebri].
AB  - CASE REPORT: We describe a fifty year old woman who complained of headache and
      transient blurring vision in her left eye. Visual acuity was normal and there was
      no pupillary defect. Ophthalmoscopy revealed left optic disc edema, whereas the
      right eye was tipified as normal. After discarding an ocular or orbital
      condition, neuroimaging and lumbar puncture leaded to diagnosis of Pseudotumor
      Cerebri. Symptoms improved after Acetazolamide treatment and lumbar punctures. A
      more detailed fundoscopy, as suggested ocular ultrasonography and CT scanner
      findings, revealed a mild papilledema in the other eye. DISCUSSION: Unilateral or
      apparently unilateral papilledema are sometimes signs of intracranial
      hypertension. Our case report highlights the difficult diagnosis of highly
      asimmetric papilledemas, and the possible delay of a neurological study.

PMID- 11592015
TI  - [Intra-bleb pigmentation after phacoemulsification].
AB  - CASE REPORT: We report the finding of an intense intra-bleb pigmentation 24 hours
      after uncomplicated phacoemulsification in an eye with previous trabeculectomy.
      In the follow-up, considerable reduction in degree of pigmentation was observed
      and intraocular pressure remained under control without medication. DISCUSSION:
      Intra-bleb pigmentation after trabeculectomy or phacotrabeculectomy has been
      recently reported by Wanichwecharungruang; however it has never been mentioned
      after isolated phacoemulsification. It is usually related with intraoperative
      pigment dispersion. A preexisting thin bleb provides a clear view of intra-bleb
      pigmentation, that appears associated with a successful filtration.

PMID- 11592016
TI  - [Crystalline extraction in progressive myopia].

PMID- 11592017
TI  - [Twenty-seven centuries of biotherapy. Tobit, the first ophthalmologist].

PMID- 11592018
TI  - [Nitrous Oxide - End of an Era - a Specific German Discussion].

PMID- 11592019
TI  - [Local anesthetics and bronchial hyperreactivity].

PMID- 11592020
TI  - [Implantable cardioverter-defibrillators, indications, function and
      anesthesiological aspects].

PMID- 11592021
TI  - [Central venous cannulation - always with ultrasound support?].
AB  - Central Venous Cannulation - Always with Ultrasound Support?.Ultrasound guided
      puncture (UGP) improves success and complication rates of central venous
      cannulation. By some authors UGP with imaging devices are strongly recommended
      for all cannulations of subclavian or internal jugular veins. In order to review
      the current literature a computer based abstract search in Medline was performed
      for the period from January 1972 to May 2000 limited by the key words
      "catheterization, central venous catheter, internal jugular vein, subclavian
      vein, axillary vein, femoral vein, ultrasound, ultrasonography, Site-Rite und
      Smart Needle". UGP of the internal jugular vein was recommended in 29 prospective
      randomized studies, 21 prospective and three retrospective studies as well as in
      several clinical reports. UGP of the subclavian vein was supported by only 4
      studies, whereas two studies did not show any improvement of puncture results
      with UGP. Due to the visualisation of the vessel and the cannula imaging
      techniques represent the "gold standard". However, with conventional Doppler
      devices nearly the same success rates can be obtained. It does not seem to be
      justified to perform every central venous cannulation with Doppler or ultrasound
      support. Each anaesthetist and intensive care physician should be able to perform
      central venous cannulation without a Doppler or ultrasound device. However, in
      cases of abnormal anatomy UGP can be helpful to prevent complications. Especially
      children, patients with coagulation disorders and physicians with limited
      experience in central venous cannulation can benefit from UGP.

PMID- 11592022
TI  - [Actions of Antithrombin (AT): experimental and clinical results].

PMID- 11592023
TI  - [200 years of nitrous oxide--at the end of an era?].

PMID- 11592024
TI  - 200 years of nitrous oxide (laughing gas)--and the end of an era?
AB  - The history of nitrous oxide is more than 200 years old and its clinical use as
      anaesthetic is more than 150 years old. The symposium discussed the question
      whether nitrous oxide should maintain its traditional role as a component of the
      anaesthetic breathing gas in everdays anaesthetic procedure or whether there are
      indications not to continue the regular use of nitrous oxide. As a matter of fact
      the continued use of nitrous oxide will not change its clinical pharmacology and
      one may argue that every year of additional experience with this drug is likely
      to increase the safety of its application. However, one has steadily to judge the
      risks of this drug against its alternatives and these have changed dramatically
      over the past decades. The new anaesthesia machines allow the combination of
      oxygen and air as breathing gas, there are new inhalational agents (e. g.
      desflurane, xenon) as controllable as nitrous oxide and new i. v. agents. As a
      conclusion of these developments the Department of Anaesthesiology at the
      Universitat Erlangen-Nurnberg has decided to cease the traditional use of nitrous
      oxide.

PMID- 11592025
TI  - [Toxicity of nitrous oxide].

PMID- 11592026
TI  - [Clinical pharmacology of nitrous oxide].

PMID- 11592027
TI  - [Xenon and other volatile anesthetic agents- mode of action].

PMID- 11592028
TI  - [Alternatives to nitrous oxide-desflurane].

PMID- 11592029
TI  - [Low flow systems with and without nitrous oxide].

PMID- 11592030
TI  - [Tension pneumothorax after subclavian vein puncture for icd-implantation without
      cardiopulmonary effects].

PMID- 11592031
TI  - [Rt-PA in fulminant perioperative lung embolism--don't beat a dead horse!].

PMID- 11592032
TI  - [Rt-PA in fulminant perioperative lung embolism--don't beat a dead horse! reply].

PMID- 11592033
TI  - Nonsense and frameshift mutations in ZFHX1B, encoding Smad-interacting protein 1,
      cause a complex developmental disorder with a great variety of clinical features.
AB  - Mutations in ZFHX1B, encoding Smad-interacting protein 1 (SIP1), have been
      recently reported to cause a form of Hirschsprung disease (HSCR). Patients with
      ZFHX1B deficiency typically show mental retardation, delayed motor development,
      epilepsy, microcephaly, distinct facial features, and/or congenital heart
      disease, in addition to the cardinal form of HSCR. To investigate the breadth of
      clinical variation, we studied DNA samples from six patients with clinical
      profiles quite similar to those described elsewhere for ZFHX1B deficiency, except
      that they did not have HSCR. The results showed the previously reported R695X
      mutation to be present in three cases, with three novel mutations-a 2-bp
      insertion (760insCA resulting in 254fs262X), a single-base deletion (270delG
      resulting in 91fs107X), and a 2-bp deletion (2178delTT resulting in 727fs754X)
      newly identified in the other three. All mutations occurred in one allele and
      were de novo events. These results demonstrate that ZFHX1B deficiency is an
      autosomal dominant complex developmental disorder and that individuals with
      functional null mutations present with mental retardation, delayed motor
      development, epilepsy, and a wide spectrum of clinically heterogeneous features
      suggestive of neurocristopathies at the cephalic, cardiac, and vagal levels.

PMID- 11592034
TI  - Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital
      muscular dystrophy with secondary laminin alpha2 deficiency and abnormal
      glycosylation of alpha-dystroglycan.
AB  - The congenital muscular dystrophies (CMD) are a heterogeneous group of autosomal
      recessive disorders presenting in infancy with muscle weakness, contractures, and
      dystrophic changes on skeletal-muscle biopsy. Structural brain defects, with or
      without mental retardation, are additional features of several CMD syndromes.
      Approximately 40% of patients with CMD have a primary deficiency (MDC1A) of the
      laminin alpha2 chain of merosin (laminin-2) due to mutations in the LAMA2 gene.
      In addition, a secondary deficiency of laminin alpha2 is apparent in some CMD
      syndromes, including MDC1B, which is mapped to chromosome 1q42, and both muscle
      eye-brain disease (MEB) and Fukuyama CMD (FCMD), two forms with severe brain
      involvement. The FCMD gene encodes a protein of unknown function, fukutin, though
      sequence analysis predicts it to be a phosphoryl-ligand transferase. Here we
      identify the gene for a new member of the fukutin protein family (fukutin related
      protein [FKRP]), mapping to human chromosome 19q13.3. We report the genomic
      organization of the FKRP gene and its pattern of tissue expression. Mutations in
      the FKRP gene have been identified in seven families with CMD characterized by
      disease onset in the first weeks of life and a severe phenotype with inability to
      walk, muscle hypertrophy, marked elevation of serum creatine kinase, and normal
      brain structure and function. Affected individuals had a secondary deficiency of
      laminin alpha2 expression. In addition, they had both a marked decrease in
      immunostaining of muscle alpha-dystroglycan and a reduction in its molecular
      weight on western blot analysis. We suggest these abnormalities of alpha
      dystroglycan are caused by its defective glycosylation and are integral to the
      pathology seen in MDC1C.

PMID- 11592036
TI  - Parent-specific complementary patterns of histone H3 lysine 9 and H3 lysine 4
      methylation at the Prader-Willi syndrome imprinting center.
AB  - The Prader-Willi syndrome (PWS)/Angelman syndrome (AS) region, on human
      chromosome 15q11-q13, exemplifies coordinate control of imprinted gene expression
      over a large chromosomal domain. Establishment of the paternal state of the
      region requires the PWS imprinting center (PWS-IC); establishment of the maternal
      state requires the AS-IC. Cytosine methylation of the PWS-IC, which occurs during
      oogenesis in mice, occurs only after fertilization in humans, so this
      modification cannot be the gametic imprint for the PWS/AS region in humans. Here,
      we demonstrate that the PWS-IC shows parent-specific complementary patterns of H3
      lysine 9 (Lys9) and H3 lysine 4 (Lys4) methylation. H3 Lys9 is methylated on the
      maternal copy of the PWS-IC, and H3 Lys4 is methylated on the paternal copy. We
      suggest that H3 Lys9 methylation is a candidate maternal gametic imprint for this
      region, and we show how changes in chromatin packaging during the life cycle of
      mammals provide a means of erasing such an imprint in the male germline.

PMID- 11592035
TI  - Evidence for a susceptibility gene, SLEV1, on chromosome 17p13 in families with
      vitiligo-related systemic lupus erythematosus.
AB  - Both systemic lupus erythematosus (SLE) and vitiligo are autoimmune disorders
      that have strong evidence of complex genetic contributions to their etiology,
      but, to date, efforts using genetic linkage to find the susceptibility genes for
      either phenotype have met with limited success. Since autoimmune diseases are
      thought to share at least some of their genetic origins, and since only a small
      minority (16 of 92) of the European-American pedigrees multiplex for SLE in our
      collection have one or more affected members with vitiligo, we hypothesized that
      these pedigrees might be more genetically homogeneous at loci important to both
      SLE and vitiligo and, hence, have increased power for detection of linkage. We
      therefore evaluated genomewide microsatellite-marker-scan data for markers at an
      average marker density of approximately 11 cM in these 16 European-American
      pedigrees and identified a significant linkage at 17p13, where the maximum
      multipoint parametric LOD score was 3.64 (P<4.3x10(-5)) and the nonparametric
      linkage score was 4.02 (P<2.8x10(-5)), respectively. The segregation behavior of
      this linkage suggests a recessive mode of inheritance with a virtually
      homogeneous genetic effect in these 16 pedigrees. These results support the
      hypotheses that SLE and vitiligo may share important genetic effects and that
      sampling on the basis of clinical covariates dramatically improves power to
      identify genetic effects.

PMID- 11592037
TI  - [Linkage disequilibrium analysis of chromosome 22 and schizophrenia in a Chinese
      population].
AB  - OBJECTIVE: To explore the molecular genetic relations of chromosome 22 and
      schizophrenia and locate the susceptibility gene of schizophrenia. METHODS: Six
      dinucleotide tandem repeat loci on chromosome 22 were chosen to analyze 126
      affected sib-pair nuclear families of schizophrenia in Chinese population by
      fluorescent labeled auto-mated genotyping and transmission/ disequilibrium
      test(TDT). RESULTS: The TDT-chi square value of IL2Rbeta was 25.30(P=0.01), which
      suggests there is linkage disequilibrium between IL2R beta and schizophrenia. The
      P vaules of the other five loci (D22S944, D22S264, D22S303, D22S278 and CYP2D6)
      were greater than 0.05. CONCLUSION: A susceptive gene of schizophrenia may be
      located in IL2Rbeta locus or adjacent region.

PMID- 11592038
TI  - [Chromosomal aberration analyzed by comparative genomic hybridization in
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To identify genetic alteration in primary sporadic nasopharyngeal
      carcinoma(NPC) in Hunan. METHODS: Comparative genomic hybridization was applied
      to investigate the genomic imbalance in a series of 20 cases of primary
      nasopharyngeal carcinomas. RESULTS: The common chromosomal alterations included
      gains of chromosomes 1q, 2, 3q, 7q,8q,12 as well as losses of chromosomes 3p, 9p,
      11q, 16q. CONCLUSION: There are multiple regions of chromosomes with copy number
      changes in NPC. The tumor suppressor genes and oncogenes on these regions may be
      involved in the development and progress of nasopharyngeal carcinoma.

PMID- 11592039
TI  - [Complex segregation analysis of systemic lupus erythematosus].
AB  - OBJECTIVE: To explore the genetic model of systemic lupus erythematosus(SLE).
      METHODS: Complex segregation analysis was performed by using statistical analysis
      for genetic epidemiology-REGTL(SAGE-REGTL). The genetic model and gene frequency
      were estimated. 300 pedigrees with SLE were collected from 300 patients as
      probands. RESULTS: The complex segregation analysis found the genetic model of
      SLE to be additive,the gene frequency 0.336. The authors believe the possibility
      of some different modes coexisting under different circumstances. The genetic
      effect on young man is stronger than that on old one. CONCLUSION: This study
      suggests that the genetic mode of SLE could be the major gene trait, and additive
      mode is the best fitted one.

PMID- 11592040
TI  - [A preliminary study of loss of heterozygosity on chromosome 14 in glioblastoma].
AB  - OBJECTIVE: In order to locate the deletion areas probably harboring tumor
      suppressor genes on chromosome 14 and provide clues for discovering novel tumor
      suppressor genes. METHODS: Fourteen loci on chromosome 14 were examined to detect
      loss of heterozygosity(LOH) in 20 cases of glioblastoma(GBM) by PCR based
      microsatellite polymorphism analyses, in which fluorescence-labeled primers and
      Perkin Elmer 377 DNA Sequencer were applied. RESULTS: 50% informative cases of
      GBM displayed LOH on chromosome 14; 38.2% of informative loci showed LOH in our
      series, in which the most frequent LOH was observed at locus D14S65(57.1%) on
      14q31-32.3 and in the chromosomal region from locus D14S63 (46.7%) to
      D14S74(47.1%) on 14q21-24.1. 32% of informative cases displayed LOH on 14p and
      50% on 14q. No microsatellite instability was observed. CONCLUSION: Loss of
      genetic material on chromosome 14q may play an important role in molecular
      genetic pathogenesis of GBM. The chromosomal regions at D14S65 on 14q31-32.3 and
      from D14S63 to D14S74 on 14q21-24.1 may harbor novel tumor suppressor genes
      associated with GBM.

PMID- 11592041
TI  - [Characteristics of APC gene mutations in colorectal tumors].
AB  - OBJECTIVE: To investigate the mutational features of adenomatous polyposis coli
      (APC) gene and their possible arising mechanism in colorectal tumors. METHODS:
      PCR-based IVSP assay (in vitro synthesized protein test) and sequence analysis
      were used to determine somatic mutations of whole APC gene in 115 cases with non
      familial adenomatous polyposis(non-FAP) colorectal tumors. RESULTS: Seventy-six
      mutated cases with 101 mutations were confirmed in the study. Analysis of the
      spectra of APC mutations revealed that frameshift mutations were more common than
      point ones(56% vs 44%), ninety-one percent of them being insertions/deletions of
      1-2 bp, particularly single A (61%) and 51% of point mutations locating at CpG
      sites. In comparison with sporadic tumors, hereditary nonpolyposis colorectal
      cancer (HNPCC) was found to have more frameshift mutations (69% vs 52%, P<0.05),
      less point mutations at CpG site (31% vs 50%, P<0.05), and a slightly lower
      frequency of mutations(53% vs 67%, P>0.05). There was no difference in mutational
      distribution of segment 3 between them (38% vs 46%, P>0.05). It was also found
      that 15 cases(20%) had double mutations with distance ranging from 7 to 1443 bp,
      suggesting the coexistance of allelic and non-allelic mutations. CONCLUSION:
      Based on the mutational spectra of APC gene in colorectal tumors, it can be
      concluded that most of gene mutations are probably related to DNA mismatch repair
      deficiency, and the APC mutational patterns of HNPCC and sporadic tumors are
      quite different. The reason of coexistance of allelic and non-allelic mutations
      needs to be investigated.

PMID- 11592042
TI  - [Analysis of apoA IV gene VNTR polymorphism in Chinese endogenous
      hypertriglyceridemics].
AB  - OBJECTIVE: To search the variation of apoA IV gene and its relation to endogenous
      hypertriglyceridemia (HTG) in Chinese population. METHODS: Forty- seven
      endogenous hypertriglyceridemics and 48 healthy subjects from a population of
      Chinese Han nationality in Chengdu area were studied using sequencing of apoA IV
      gene amplified by polymerase chain reaction (PCR). RESULTS: The frequency of
      (CTGT)(3) allele in Chinese control group was significantly different from that
      reported in German Caucasians (0.253 vs 0.607, P<0.01) and in Italian Caucasians
      (0.253 vs 0.522, P<0.01), but not different from that reported in Japanese (0.253
      vs 0.262, P>0.05). The frequency of (CTGT)(3) allele showed no significant
      difference between normal control and HTG groups(0.223 vs 0.281,P>0.05). In the
      healthy control group, the subjects with genotype 3/3 of VNTR site had a higher
      serum mean concentration of LDLC as compared to those with genotype 3/4 (3.698 +/
      0.67 mmol/L vs 2.974 +/- 0.54 mmol/L, P<0.05). CONCLUSION: The results suggest
      that VNTR polymorphism in apoA IV gene is associated with healthy control
      subjects to some extent in Chinese population.

PMID- 11592043
TI  - [Sequencing-based typing of HLA-DPB1 and DQB1 exon 2 in patients with type 1
      diabetes mellitus].
AB  - OBJECTIVE: To investigate the correlation between type 1 diabetes mellitus
      susceptibility and HLA-DPB1 and DQB1 genes in Shandong Han population. METHODS:
      HLA-DPB1 and DQB1 genes analysis were performed by sequencing-based typing in 52
      type 1 diabetes mellitus patients and 38 normal controls. RESULTS: The frequency
      of DPB1*2201 in diabetics was significantly higher than that in controls(26.92%
      vs 5.26%, P<0.01), but the frequency of DPB1*0402 in diabetics was significantly
      lower than that in controls(11.54% vs 34.21%, P<0.01). The frequencies of
      DQB1*0201, *0303 and *0604 in diabetics were higher than those in controls
      (24.04% vs 10.53%, P< 0.01; 22.12% vs 6.58%, P<0.05; 19.23% vs 7.89%, P<0.05),
      while the frequency of DQB1*0301 in diabetics was significantly lower than that
      in controls (4.81% vs 25.00%, P<0.01). CONCLUSION: DPB1*2201, DQB1*0201, *0303
      and *0604 may be susceptible alleles, and DPB1*0402 and DQB1*0301 may be
      protective alleles in patients with type 1 diabetes mellitus.

PMID- 11592044
TI  - [The association between SA gene and essential hypertension in Han Chinese].
AB  - OBJECTIVE: To evaluate the linkage of SA gene locus to essential hypertension(EH)
      in affected Han Chinese sib pairs and to ascertain the association of SA gene
      CT79 polymorphism with essential hypertension in Han Chinese hypertensives.
      METHODS: In Han Chinese at Shanghai, 96 random individuals, 80 essentially
      hypertensive sib pairs with hypertensive family history, 200 essential
      hypertensives with hypertensive family history and 200 normotensive control(NC)
      subjects without such family history were enrolled in these serial studies. MF
      PCR-SSCP technique was applied to detect the frequency distributions of SA gene
      microsatellite D16S3046, D16S3136 and D16S3068. The linkage of SA gene locus to
      essential hypertension was analyzed by Green's IBS for affected siblings. SA gene
      variant was screened by PCR-SSCP- silver staining and confirmed by DNA
      sequencing, then an association study was performed to determine whether such
      variant was associated with essential hypertension. RESULTS: The frequency
      distributions of SA gene microsatellites D16S3046, D16S3136 and D16S3068 were of
      high polymorphism. The polymorphism information contents of D16S3046, D16S3136
      and D16S3068 were 0.86, 0.82 and 0.80, and the heterozygosities 0.88, 0.71 and
      0.77. The linkage of SA gene locus to essential hypertension was not observed;
      the linkage analysis t values of D16S3046,D16S3136 and D16S3068 were 0.972, 0.622
      and 0.236, and the P values 0.384, 0.543 and 0.871, respectively. The C two head
      right arrow T substitution was confirmed, but there was no association of such
      variant with essential hypertension. The frequency distributions of genotypes and
      alleles in the hypertensive group were not significantly different from those in
      the normotensive group (P>0.05). CONCLUSION: SA gene is not linked to or
      associated with essential hypertension in Han Chinese. SA gene may not be a
      susceptible gene contributing to the development of essential hypertension in Han
      Chinese.

PMID- 11592045
TI  - [The role of beta3-adrenergic receptor Trp/Arg mutation in childhood obesity].
AB  - OBJECTIVE: To understand with greater clearness the role of beta3- adrenergic
      receptor Trp/Arg mutation in childhood obesity. METHODS: One hundred and seventy
      seven children, aged 6-12 years, were selected. The genotype was detected by
      restricted fragment length polymorphism, the children's dietaries were surveyed
      by a 3-day recalling and recording method. Their height, weight were measured,
      and the data on their living habits were collected from their parents. RESULTS:
      The intake of total amount of food and energy of obese children were higher in
      children with Trp/Trp genotype, but there was no difference between the obese and
      non-obese children with Trp/Arg genotype. Among children with the Trp/Arg
      genotype, obese children were less active and did less exercise, they slept more,
      but there was no difference among children with Trp/Trp genotype. CONCLUSION: The
      children with beta3-AR Trp/Arg mutation may become obese because of the low
      energy metabolism; less active and exercise may increase the risk of obesity.

PMID- 11592046
TI  - [Association of apolipoprotein E gene polymorphism with early-onset coronary
      heart disease and its effect on plasma lipid levels].
AB  - OBJECTIVE: To detect the association of apolipoprotein E(apoE) gene polymorphism
      with early-onset coronary heart disease(CHD) and to evaluate the effect of apoE
      gene polymorphism on plasma lipid levels. METHODS: The apoE genotypes of 52 early
      onset CHD patients (aged 38-55 years), 161 aged CHD patients and 180 controls
      were determined by PCR-RFLP. Plasma lipid levels were measured by using routine
      methods. RESULTS: Five genotypes of apoE, E3/3, E4/4, E3/2, E4/3 and E4/2 were
      detected in this study. Statistically differences in apoE4/3 and epsilon4
      frequencies between early-onset and aged CHD patients and controls were seen
      (P<0.05). The frequency of epsilon4 in the early-onset CHD patients was higher
      than that in the aged CHD patients. epsilon4 and epsilon2 alleles also
      differently affected the plasma total cholesterol and low density lipoprotein
      cholesterol levels. CONCLUSION: These results suggest that apoE gene polymorphism
      is in association with the occurrence and development of early-onset CHD and it
      affects the plasma lipid levels.

PMID- 11592047
TI  - [Allele sequences and population genetics of pentanucleotide tandem repeat
      D6S957].
AB  - OBJECTIVE: Pentanucleotide tandem repeat loci are useful markers of short tandem
      repeat (STR) for genetic analysis. We focused on the analysis of the DNA sequence
      for each allele at the pentanucleotide STR locus D6S957 in order to understand
      their structures in the human genome and to construct human allelic ladder, which
      is necessary for forensic DNA typing. In order to evaluate the forensic
      applicability of D6S957, we investigated the genotype distributions and allele
      frequencies in major ethnic groups. METHODS: A total of 230 samples from
      unrelated individuals were analyzed by PCR. Allele determination was carried out
      by comparison with a sequenced human allelic ladder made in-house. An example of
      each allele was sequenced on an ABI 377 automated sequencer. RESULTS: This
      pentanucleotide STR exhibited a minimal amount of stutter and provided easily
      interpretable results. Eight alleles were found in these populations. No evidence
      of deviation from Hardy-Weinberg equilibrium was observed. In 64 confirmed
      father/mother/child triplets no mutation events were observed. The mutation rate
      was indirectly estimated at 2.5 x 10(-5) using a maximum likelihood method.
      CONCLUSION: D6S957 is a useful marker for forensic casework and paternity
      analysis.

PMID- 11592048
TI  - [The study of PAI-1 promotor region gene polymorphism in cerebrovascular
      disease].
AB  - OBJECTIVE: To investigate the relationship between the plasminogen activator
      inhibitor-1(PAI-1) gene polymorphism and cerebrovascular disease and detect
      whether it plays an important role in the pathogenesis of cerebrovascular
      disease. METHODS: Peripheral blood leukocytes samples were collected from 60
      normal controls, 65 patients with acute cerebral infarction (CI) and 31
      hypertensives complicated with cerebral hemorrhage. The 4G/5G allele polymorphism
      in the PAI-1 gene promotor region of the leukocytes was genotyped by polymerase
      chain reaction. The plasma PAI-1 activity was assayed by ELISA. RESULTS: The
      plasma PAI-1 activity level in the CI group was significantly higher than those
      in the other two groups. PAI-1 level in 4G allele homozygous genotype was
      significantly higher than the PAI-1 levels in 4G/5G heterozygous and 5G
      homozygous. Although PAI-1 level was higher in 4G/5G heterozygous genotype than
      in 5G homozygous, the difference was not statistically significant. There were
      significant differences between acute cerebral infarction PAI-1 gene polymorphism
      and controls (P<0.05), and the frequencies of 4G/4G genotype in patients with
      acute cerebral infarction (43.08%) were higher than those in normal controls
      (20.00%, P<0.05). There were no significant differences between hypertensives
      complicated with hemorrhage (25.81%) and controls (P>0.05), and the PAI-1 levels
      of the 4G/4G genotype in the female patients with CI were higher than those in
      the male patients with CI of the same genotype. CONCLUSION: The results suggest
      that PAI-1 gene polymorphism may be a susceptible factor to acute cerebral
      infarction in Chinese, and 4G allele homozygous genotype may be the major risk
      factor for acute cerebral infarction, and it may be especially an independent
      risk factor of cerebral infarction in female patients.

PMID- 11592049
TI  - [Mutations of mitochondrial 12S rRNA gene in type 2 diabetes].
AB  - OBJECTIVE: To investigate mutations at points 1310, 1438 and 1442 of
      mitochondrial 12S rRNA gene in Chinese type 2 diabetes and screen for new
      mutations associated with type 2 diabetes in this area. METHODS: The
      mitochondrial DNAs (mtDNAs) of 86 patients with type 2 diabetes and those of 70
      normal controls were analyzed using PCR-SSCP and PCR product direct sequencing
      technique. RESULTS: One patient was found with the mitochondrial DNA G --> A
      mutation at point 1438, and one with the G two head right arrow A mutation at
      point 1442, whereas none of the normal controls was found to have mutation at
      these two points. No C --> T mutation at nucleotide pair 1310 of the
      mitochondrial 12S rRNA gene was identified. CONCLUSION: The G --> A mutation at
      points 1438 and 1442 is likely to be associated with the development of type 2
      diabetes; the occurrence of the C -->T mutation at point 1310 is probably rare in
      the blood cells, and the development of type 2 diabetes may be related to
      heterogeneity in mitochondrial genetic changes.

PMID- 11592050
TI  - [Analysis of several genes using primer extension preamplification based on
      individual cell].
AB  - OBJECTIVE: To analyze several genes at the same time in one individual cell using
      primer extension preamplification (PEP). METHODS: The whole genome of individual
      cell was preamplified by PEP using 10 base random oligonucleotides. The
      aliquots(5 mu liter) from PEP were used to amplify SRY, ZP(3), RhCE, RhD and F
      VIII genes by nested PCR. RESULTS: The five genes could be amplified following
      PEP-PCR. Lymphocyte of four genotypes were diagnosed by PEP-PCR; correct
      diagnoses were obtained in 95.6%. CONCLUSION: At least five genes can be analyzed
      by PEP-PCR based on one individual cell in this laboratory. This method could be
      used in preimplantation genetic diagnosis and noninvasive prenatal diagnosis.

PMID- 11592051
TI  - [Gene diagnosis of factor VIII gene inversion by LD-PCR for 60 patients with
      severe hemophilia A].
AB  - OBJECTIVE: To identify factor VIII(F VIII) gene inversion among 60 patients with
      severe hemophilia A (HA) in Tianjin region. METHODS: DNA was extracted from
      peripheral blood of HA patients; F VIII gene inversion was identified by long
      distance-polymerase chain reaction(LD-PCR) and 0.6% agarose gel electrophoresis.
      Those with only 11 kb band were diagnosed as the cases of F VIII gene inversion.
      Those with only 12 kb band were identified as wild type(non-inversion), and those
      with both 11 kb and 12 kb bands were recognized as inversion carriers. RESULTS:
      There were 21 patients with F VIII gene inversion, accounting for 35% of the 60
      patients with severe HA. CONCLUSION: LD-PCR can be used to detect the F VIII gene
      inversion directly; it is an effective method for the gene diagnosis of severe
      hemophilia A.

PMID- 11592052
TI  - [Progress in researches on the molecular genetics of facioscapulohumeral muscular
      dystrophy].
AB  - Facioscapulohumeral muscular dystrophy(FSHD) is an autosomal dominant
      neuromuscular disorder characterized by progressive weakness of the facial,
      shoulder and upper arm muscles. The major gene involved has been mapped to
      chromosome 4q35. There is the evidence for genetic heterogeneity. The FSHD-
      associated DNA rearrangements are due to deletions of integral copies of the 3.3
      kb tandem repeated unit from the subtelomeric region on chromosome 4q35. A
      valuable molecular diagnostic test for FSHD has been created with the use of p13E
      11 probe to detect the EcoR I/Bln I double digestion fragment which is usually
      smaller in FSHD patient than in normal indivdual. Since the FSHD gene has not
      been identified yet, the exact molecular pathogenesis of FSHD remains unclear.
      The hypothesis of position effect variegation has been postulated as the
      underlying genetic mechanism of FSHD. FRG1 (FSHD region gene 1) from human
      chromosome 4q35 is identified as a candidate gene for FSHD. A significant
      correlation between the size of rearrangements associated with FSHD and the
      clinical phenotype has been found. The various rearrangement fragment size may
      explain the wide range of clinical severity in FSHD.

PMID- 11592053
TI  - Peptide/benzodiazepine hybrids as ligands of CCK(A) and CCK(B) receptors.
AB  - The (neuro)hormones gastrin and cholecystokinin (CCK) share a common C-terminal
      tetrapeptide amide sequence that has been recognized as the message portion while
      the N-terminal extensions are responsible for the CCK(A) and CCK(B) receptor
      subtype selectivity and avidity. 1,4-Benzodiazepine derivatives are potent and
      selective antagonists of these receptors, and according to comparative molecular
      field analysis, the structures of these nonpeptidic compounds could well mimic
      the message sequence of the peptide agonists at least in terms of spatial array
      of the aromatic residues. Docking of a larger series of low molecular weight
      nonpeptide antagonists to a homology modeling derived CCK(B) receptor structure
      revealed a consensus binding mode that is further validated by data from site
      directed mutagenesis studies of the receptors. Whether this putative binding
      pocket of the nonpeptide antagonists is identical to that of the message portion
      of the peptide agonists, or whether it is distinct and spatially separated, or
      overlapping, but with distinct interaction sites, is still object of debate.
      Using a 1,4-benzodiazepine core amino-functionalized at the C3 position, related
      tryptophanyl derivatives were synthesized as mimics of the tetrapeptide and
      subsequently extended N-terminally with gastrin and CCK address sequences. All
      hybrid constructs were recognized as antagonists by the CCK(A) and CCK(B)
      receptors, but their address portions were incapable of enhancing in significant
      manner selectivity and avidity. Consequently, the binding of the
      peptide/benzodiazepine hybrids has to be dictated mainly by the benzodiazepine
      moiety, which apparently prevents optimal interactions of the address peptides
      with extracellular receptor subdomains. These findings would strongly support the
      view of distinct binding sites for the message portion of the peptide agonists
      and the benzodiazepine-based nonpeptide antagonists.

PMID- 11592054
TI  - Nonionic amphiphilic polymers derived from Tris(hydroxymethyl)-acrylamidomethane
      keep membrane proteins soluble and native in the absence of detergent.
AB  - A new family of amphipols-amphiphilic polymers designed to form water-soluble
      complexes with membrane proteins-was synthesized by free-radical telomerization
      of Tris(hydroxymethyl)-acrylamidomethane (THAM) and derivatized THAM. Some of
      these polymers were found to prevent aggregation and denaturation of two model
      membrane proteins, bacteriorhodopsin and cytochrome b(6) f, in the absence of
      detergent micelles.

PMID- 11592055
TI  - Structural basis of DNA recognition by anticancer antibiotics, chromomycin A(3),
      and mithramycin: roles of minor groove width and ligand flexibility.
AB  - Anticancer antibiotics, chromomycin A(3) (CHR) and mithramycin (MTR), inhibit
      cellular processes like transcription and replication, by binding reversibly to
      double-stranded DNA via minor groove, in the presence of bivalent metal ions like
      Mg(2+) with GC base specificity. Here, we have attempted to assess the roles of
      two parameters-namely DNA groove dimension and flexibility of the ligand-in the
      structural recognition between the ligands, (drug)(2)Mg(2+) and DNA. For the
      purpose we have employed three synthetic oligonucleotides with minor groove width
      lying between B- and A-type structures as model DNA sequences: d(GCGCGCGC)(2) in
      B-form, d(CCGGCGCCGG)(2) in B-form with unusual wide minor groove, and
      (GGGGCCCC)(2) in A-form. Association of the (drug)(2)Mg(2+) with the oligomers
      have been probed using spectroscopic techniques like absorbance, fluorescence,
      and CD. The binding and thermodynamic parameters for the different association
      processes have also been characterized. Major conclusions from the above studies
      are as follows. Groove size of the oligomers influences the conformation of the
      bound ligand. A saccharide dependent variation in structural rigidity of the
      ligands, (MTR)(2)Mg(2+) and (CHR)(2)Mg(2+), has been observed that leads to
      differences in the energetics of recognition of the same DNA sequence by the two
      ligands. In contrast to (CHR)(2)Mg(2+), higher flexibility in (MTR)(2)Mg(2+)
      makes its conformation in the DNA bound form less sensitive to the groove
      dimension of DNA.

PMID- 11592056
TI  - Study on the packing geometry, stoichiometry, and membrane interaction of three
      analogs related to a pore-forming small globular protein.
AB  - A de novo designed pore-forming small globular protein (SGP) with antitumor
      activity consists of four helices: 3 basic amphipathic helices composed of Leu
      and Lys surrounding a central hydrophobic helix composed of oligoalanine. These
      helices are connected by a beta-turn-forming sequence and two beta-turn
      unfavorable ones (S. Lee, T. Kiyota, T. Kunitake, E. Matsumoto, S. Yamashita, K.
      Anzai, and G. Sugihara Biochemistry 1997, Vol. 36, pp. 3782-3791). In the present
      work, we designed and synthesized three new SGP analogs in order to study the
      stoichiometric packing geometry and stability of SGP. The replacement of alanines
      in the central helix of SGP with leucines (SGP-L), which make the helix much
      larger in size and more hydrophobic, resulted in an equilibrium of monomeric
      trimeric structure. The replacement of some Lys residues by Glu residues in the
      hydrophilic regions of the amphipathic helices (SGP-E) led to a decrease in
      helical content and the formation of an equilibrium of monomeric-trimeric
      structure. The alteration of beta-turn regions with Gly residues, which makes
      these regions flexible (SGP-G), established an equilibrium of monomeric-dimeric
      states in buffer. The hydrophobic alpha-helix of SGP-L penetrated into the lipid
      bilayers in a manner that stabilized model membranes and biomembranes, whereas
      the central helices of SGP-G and -E destabilized them by forming channels. SGP
      and its analogs may be a useful model to study the role of the hydrophobic and
      hydrophilic regions in the formation of monomer-oligomer of proteins and to
      better understand the insertion of membrane targeting proteins into biomembranes.

PMID- 11592057
TI  - Mechanical characterization of network formation during heat-induced gelation of
      whey protein dispersions.
AB  - The formation of gel network structures during isothermal heating of whey protein
      aqueous dispersions was probed by mechanical spectroscopy. It was anticipated
      that the pathway of the sol-to-gel transition of whey protein dispersions is
      quite different from that of ordinary cross-linking polymers (e.g., percolation
      type transition), since aqueous solutions of native whey proteins have been shown
      to be highly structured even before gelation, in our previous study. At 20
      degrees C, aqueous dispersions of beta-lactoglobulin, the major whey protein, and
      those of whey protein isolate (WPI), a mixture of whey proteins, exhibited solid
      like mechanical spectra, i.e., the predominant storage modulus G' over the loss
      modulus G", in a certain range of the frequency omega (1-100 rad/s), regardless
      of the presence or absence of added NaCl. The existence of the added salt was,
      however, a critical factor for determining transitions in mechanical spectra
      during gelation at 70 degrees C. beta-Lactoglobulin dispersions in 0.1 mol/dm(3)
      NaCl maintained the solid-like nature during the entire gelation process and,
      after passing through the gelation point, satisfied parallel power laws (G'
      approximately G" approximately omega(n)) that have been proposed for a critical
      gel (i.e., the gel at the gelation point) that possesses a self-similar or
      fractal network structure. In contrast, beta-lactoglobulin dispersions without
      added salt exhibited a transition from solid-like [G'(omega) > G"(omega)] to
      liquid-like [G'(omega) < G"(omega)] mechanical spectra before gelation, but no
      parallel power law behavior was recognized at the gelation point. During extended
      heating time (aging), beta-lactoglobulin gels with 0.1 mol/dm(3) NaCl showed
      deviations from the parallel power laws, while spectra of gels without added NaCl
      approached the parallel power laws, suggesting that post-gelation reactions also
      significantly affect gel network structures. A percolation-type sol-to-gel
      transition was found only for WPI dispersions without added salt.

PMID- 11592058
TI  - CD antigens 2001.

PMID- 11592059
TI  - IL-10 mediates susceptibility to Leishmania donovani infection.
AB  - Human visceral leishmaniasis (VL) results in a severe and potentially fatal
      systemic disease, accompanied by cellular immune depression. The production of IL
      10 correlates with ongoing disease and it has been suggested that the cellular
      immune depression that accompanies active disease may be due to a predominance of
      IL-10 production rather than a lack of IFN-gamma production, which is essential
      for optimal macrophage activation and parasite elimination. To examine the role
      of IL-10 in resistance during L. donovani infection (a causative agent of VL),
      the course of infection was examined in mice lacking the gene for IL-10. BALB/c
      IL-10-/-, as well as C57BL/6 IL-10-/- mice, were highly resistant to L. donovani
      infection, as evidenced by liver parasite burdens which were tenfold lower than
      those in control mice after 14 days of infection. Enhanced resistance was
      accompanied by increased production of IFN-gamma and nitric oxide in BALB/c IL-10
      /- mice. Susceptibility to infection in BALB/c IL-10-/- mice was enhanced
      following in vivo treatment with a neutralizing antibody to IFN-gamma or IL-12.
      Together these studies demonstrate for the first time that IL-10 is a critical
      component of the immune response that inhibits resistance to L. donovani.

PMID- 11592060
TI  - Peroxisome proliferator-activated receptor gamma activators affect the maturation
      of human monocyte-derived dendritic cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma ), a member of the
      nuclear receptor superfamily, has recently been described as a modulator of
      macrophage functions and as an inhibitor of T cell proliferation. Here, we
      investigated the role of PPARgamma in dendritic cells (DC), the most potent
      antigen-presenting cells. We showed that PPARgamma is highly expressed in
      immature human monocyte-derived DC (MDDC) and that it may affect the
      immunostimulatory function of MDDC stimulated with lipopolysaccharide (LPS) or
      via CD40 ligand (CD40L). We found that the synthetic PPARgamma agonist
      rosiglitazone (as well as pioglitazone and troglitazone) significantly increases
      on LPS- and CD40L-activated MDDC, the surface expression of CD36 (by 184% and
      104%, respectively) and CD86 (by 54% and 48%), whereas it reduces the synthesis
      of CD80 (by 42% and 42%). Moreover, activation of PPARgamma resulted in a
      dramatic decreased secretion of the Th1-promoting factor IL-12 in LPS- and CD40L
      stimulated cells (by 47% and 62%), while the production of IL-1beta, TNF-alpha,
      IL-6 and IL-10 was unaffected. Finally, PPARgamma ligands down-modulate the
      synthesis of IFN-gamma -inducible protein-10 (recently termed as CXCL10) and
      RANTES (CCL5), both chemokines involved in the recruitment of Th1 lymphocytes (by
      49% and 30%), but not the levels of the Th2 cell-attracting chemokines,macrophage
      derived chemokine (CCL22) and thymus and activation regulated chemokine (CCL17),
      in mature MDDC. Taken together, our data suggest that activation of PPARgamma in
      human DC may have an impact in the orientation of primary and secondary immune
      responses by favoring type 2 responses.

PMID- 11592061
TI  - Sequences associated with the mouse Smu switch region are important for
      immunoglobulin heavy chain transgene expression in B cell development.
AB  - Analyses of H-chain transgenes have indicated that sequences situated between the
      mu intronic enhancer and the Cmu exons are important for mu gene expression. We
      have analyzed several variant mu transgenes and find that a sequence element
      located within or just upstream of Smu is important for mu transgene expression
      in both immature and mature B cells. This Smu -associated element appears to be
      required for functional mu expression in small, resting pre-B cells but not in
      proliferating pre-B cells. Our results also indicate that this element is
      responsible for previously reported differential transgene expression in resting
      and activated/proliferating mature B cells. However, our studies of knockout mice
      show that deletion of the Smu -associated element from the endogenous IgH locus
      does not alter early B cell maturation. This indicates that other elements within
      the H-chain locus can replace the function of the Smu -associated element at
      least to the mature B cell stage. Surprisingly, we also find that Smu deletion in
      the IgH locus does not affect levels of the sterile germ-line mu transcripts that
      are involved in B cell class switching, even though S-region sequences have been
      indicated to be important for the production of analogous germ-line transcripts
      for other isotypes.

PMID- 11592062
TI  - Vascular adhesion protein-1 (VAP-1) mediates lymphocyte-endothelial interactions
      in chronic kidney rejection.
AB  - The pathogenesis of chronic kidney rejection characterized by persistent low
      level inflammation and intimal thickening of the arteries in the graft remains
      poorly understood. We studied whether two important endothelial adhesion
      molecules, vascular adhesion molecule-1 (VAP-1) and peripheral node addressin
      (PNAd), would contribute to the lymphocyte recruitment into the rejected organ.
      VAP-1 was found to be present both in the normal kidney and prominently also in
      the chronically rejected kidneys. In the kidney VAP-1 was a homodimeric
      sialoglycoprotein expressed in peritubular capillaries, but not on glomerular
      endothelium or on tubular cells. In contrast, PNAd was absent from all kidney
      samples, indicating that kidney inflammation differs from other sites of chronic
      inflammation. Blocking of VAP-1 with mAbs abolished > 50 % of lymphocyte binding
      to renal vessels in rejected kidney in in vitro adhesion assays. Levels of
      circulating soluble VAP-1 (sVAP-1) decreased back to normal levels in patients
      with well-functioning transplants. These results are the first evidence that VAP
      1 is able to mediate leukocyte binding into a rejected organ. Thus, anti-adhesive
      therapies targeting VAP-1 may be useful in controlling chronic kidney graft
      rejection.

PMID- 11592063
TI  - LAP, a lymphocyte activation gene-3 (LAG-3)-associated protein that binds to a
      repeated EP motif in the intracellular region of LAG-3, may participate in the
      down-regulation of the CD3/TCR activation pathway.
AB  - The threshold, extent and termination of TCR activation is controlled in part by
      inhibitory co-receptors expressed on activated T cells. The lymphocyte activation
      gene product (LAG-3), a ligand for MHC class II molecules co-caps with the
      CD3/TCR complex and inhibits cell proliferation and cytokine secretion in
      response to CD3 signaling. We first investigated whether LAG-3 is localized in
      activated T cells in detergent-resistant membrane rafts enriched in
      glycosphingolipids and cholesterol. We showed that both LAG-3 and MHC class II
      are present in the cell fraction of glycosphingolipid-rich complexes (GSL
      complexes) before the assembly of the immunological synapse by CD3/TCR complex
      cross-linking. Using the LAG-3 intracytoplasmic region as bait in the yeast two
      hybrid cloning system, we next identified a novel protein termed LAP for LAG-3
      associated protein. LAP is encoded by a 1.8-kb RNA message in lymphocytes and
      encodes a 45-kDa protein that is expressed in most tissues. We showed that LAP
      binds specifically in vitro and in vivo to the Glu-Pro (EP) repeated motif
      present in the LAG-3 intracytoplasmic region. LAP also binds to the EP motif of
      another functionally important receptor, the PDGFR. Thus, LAP is a candidate
      molecule for a new type of signal transduction and/or coupling of clustered rafts
      to the microtubule networks that could explain how negative signaling of co
      receptors may occur through molecules devoid of any immunoreceptor tyrosine-based
      inhibitory motif consensus sequence.

PMID- 11592064
TI  - "Tolerosomes" are produced by intestinal epithelial cells.
AB  - The development of immunological tolerance to orally fed antigens depends on the
      sampling, processing and transportation events followed in the intestinal
      epithelium. We present here a description of a "tolerosome": a supra-molecular,
      exosome-like structure assembled in and released from the small intestinal
      epithelial cell. The tolerosome is a approximately 40 nm large vesicular
      structure that carries MHC class II (MHC II) with bound antigenic peptides
      sampled from the gut lumen. Tolerosomes isolated from serum shortly after antigen
      feeding or from an in vitro pulsed intestinal epithelial cell line are fully
      capable of inducing antigen specific tolerance in naive recipient animals.
      Purified tolerosomes represent a structure by which fed antigens can be
      efficiently presented to the immune system. Removal of the tolerosomes from serum
      by ultracentrifugation or absorption of MHC II results in abrogated tolerance
      development.

PMID- 11592065
TI  - Tissue-specific segregation of TCRgamma delta+ NKT cells according to phenotype
      TCR repertoire and activation status: parallels with TCR alphabeta+NKT cells.
AB  - Whereas the majority of NKT cells in the mouse express an alpha beta TCR
      (NKTalpha beta cells), a small subset of NKT cells express a gamma delta TCR
      (NKTgamma delta). Here we have systematically analyzed the phenotype, TCR
      repertoire and activation status of NKTgamma delta cells in the thymus, liver,
      spleen and bone marrow of normal C57BL/6 mice. Our data indicate that NKTgamma
      delta cells segregate in a tissue-specific manner according to these parameters.
      While most NKTgamma delta cells in the thymus and liver have a recently activated
      CD62L(lo) phenotype and a TCR repertoire that is heavily biased to Vgamma1.1 and
      Vdelta6.3, the majority of NKTgamma delta cells in the spleen and bone marrow are
      CD62L(hi) and have a much less biased TCR repertoire. Moreover, expression of NK
      markers is high on NKTgamma delta cells in spleen and bone marrow but low in
      thymus and liver. Collectively our results reveal a tissue-specific segregation
      of NKTgamma delta cells that is strikingly similar to that recently described for
      CD1d-dependent and Cd1d-independent NKTalpha beta cells. We therefore propose
      that chronic TCR activation by tissue-specific endogenous ligands is a generic
      property of NKT cells of both the alpha beta and gamma delta lineages.

PMID- 11592066
TI  - Immunization with the adjuvant MF59 induces macrophage trafficking and apoptosis.
AB  - The mechanisms associated with the immunostimulatory activity of vaccine
      adjuvants are still poorly understood. We have undertaken a study to determine
      whether antigen-presenting cell trafficking is modified by administration of the
      submicron emulsion adjuvant MF59. We investigated the fate of inflammatory
      macrophages after intramuscular injection of the antigen herpes simplex virus gD2
      with fluorescence-labeled MF59. A homogeneous population of macrophages
      infiltrated the muscle, internalized adjuvant and expressed markers
      characteristic of mature macrophages over a 48-h period. Macrophage influx to the
      injection site was reduced by 70% in mice deficient for the chemokine receptor 2
      (CCR2). Two distinct cell populations were shown to contain fluorescence-labeled
      MF59 in the draining lymph node at 48 h post injection. The first population had
      a round morphology, exhibited bright fluorescence, was located in the subcapsular
      sinus, and was apoptotic. The second population had a dendritic morphology, was
      weakly fluorescent, and was located in the T cell area where adjuvant-containing
      apoptotic bodies identified by TUNEL labeling were present. We propose that lymph
      node-resident dendritic cells can acquire antigen and MF59 after intramuscular
      immunization by uptake of the apoptotic macrophages.

PMID- 11592067
TI  - Valpha gene replacement in a TCRalpha knock-in mouse.
AB  - Using a TCRalpha chain knock-in mouse, we demonstrate that V-gene replacement can
      operate in the T cell receptor alpha locus. Functional TCRalpha chain transcripts
      generated by Valpha-gene replacement at the site of the Valpha-embedded heptamer
      were identified in splenic T cells. This finding shows that Valpha-gene
      replacement can likely be used to shape the peripheral T cell repertoire. The
      conservation of the embedded heptamer in most Valpha segments adds support to the
      notion that V-gene replacement is a mechanism maintained to diversify the immune
      system and that argues that it is common to B and T cells.

PMID- 11592068
TI  - Synergistic effect of IFN-gamma and human cytomegalovirus protein UL40 in the HLA
      E-dependent protection from NK cell-mediated cytotoxicity.
AB  - Human CMV (HCMV) has evolved several strategies to evade the immune system of the
      infected host. Here, we investigated the role of the HCMV-encoded protein UL40 in
      the modulation of NK cell lysis. UL40 carries in its leader sequence a nonameric
      peptide similar to that found in many HLA class I molecules leader sequences.
      This peptide up-regulates the expression of HLA-E, the ligand for the NK cell
      inhibitory receptor CD94/NKG2A. The UL40-encoded HLA-E-binding peptide was
      present in all HCMV clinical (4636, 13B, 109B, 3C) and laboratory (AD169) strains
      analyzed. However, transfection of UL40 in different cell lines (293T, 721.221,
      K562) did not consistently confer protection from NK lysis (as measured using NKL
      and the newly generated NK line Nishi), despite a moderate up-regulation of HLA
      E. Interestingly, combined transfection and treatment with IFN-gamma increased
      the inhibitory effect, via an HLA-E- and CD94/NKG2A-dependent mechanism. Although
      cells transfected with UL40 derived from either AD169 or 3C showed protection
      from NK cell lysis, infection of fibroblasts with the viruses resulted in a
      strong inhibition only with the clinical strain 3C. Our results suggest that UL40
      and IFN-gamma-dependent up-regulation of HLA-E is only one possible mechanism to
      avoid NK cell recognition of HCMV infected cells.

PMID- 11592069
TI  - High expression and autoinduction of monocyte chemoattractant protein-1 in
      scleroderma fibroblasts.
AB  - Systemic sclerosis (SSc) is a connective tissue disease with unknown etiology
      characterized by excessive deposition of extracellular matrix in the skin as well
      as various internal organs. In the early stages of SSc, inflammatory infiltrates
      of mononuclear cells are found in the dermis, which is associated with increased
      collagen synthesis produced by activated fibroblasts. Monocyte chemoattractant
      protein-1 (MCP-1) is a predominant monocyte chemoattractant secreted by a variety
      of cell types, and recent in vivo and in vitro studies suggest the involvement of
      MCP-1 in tissue fibrosis. Here we demonstrate that cultured scleroderma
      fibroblasts, compared to fibroblasts from control skin, spontaneously express
      significantly elevated MCP-1 levels. Interestingly, exogenously administered MCP
      1 stimulated autoinduction of MCP-1 mRNA. This effect was specific to scleroderma
      fibroblasts and abrogated by actinomycin D. These findings suggest that MCP-1
      plays an important role in the induction of scleroderma by MCP-1 release from
      fibroblasts, which results in recruitment of monocytes to the skin. Moreover,
      increased responsiveness of scleroderma fibroblasts to MCP-1 could result in a
      continuation of the fibrotic response.

PMID- 11592070
TI  - Frequency, heterogeneity and encephalitogenicity of T cells specific for myelin
      oligodendrocyte glycoprotein in naive outbred primates.
AB  - Auto-reactive T cells present in healthy subjects remain in a state of
      unresponsiveness, but may trigger autoimmunity under various situations. Although
      myelin oligodendrocyte glycoprotein (MOG) is a potential target antigen in
      multiple sclerosis (MS), MOG-reactive T cell responses are present in the blood
      of both healthy subjects and MS-affected individuals. To investigate the disease
      inducing potential and regulation of these autoreactive T cells in healthy
      outbred populations, we have characterized MOG-reactive T cell clones obtained by
      limiting dilution from peripheral blood of unimmunized C. jacchus marmosets. We
      report an extraordinarily high prevalence of circulating MOG-reactive T cells in
      these naive animals (2.6 +/- 1.4 / 10(5) PBMC), and a broadly diverse repertoire
      of epitope recognition encompassing at least three regions within the
      extracellular domain of MOG. Adoptive transfer of a MOG21-40-specific T cell
      clone resulted in mild clinical experimental allergic encephalomyelitis,
      characterized pathologically by rare foci of inflammation and minimal
      demyelination. We conclude that MOG-reactive T cells are present in healthy
      primates at a highly prevalent frequency, and are potentially capable of
      triggering central nervous system autoimmunity. Expansion of these autoreactive T
      cells must be tightly controlled to maintain immune homeostasis in healthy
      individuals.

PMID- 11592071
TI  - An abrupt and concordant initiation of apoptosis: antigen-dependent death of CD8+
      CTL.
AB  - The ability of CD8+ cytotoxic T lymphocytes (CTL) to clear viral infections may
      be limited when high avidity CTL encounter supra-optimal antigen density on
      antigen-presenting cells (APC) and undergo antigen-dependent apoptosis of CTL
      (ADAC). Previously, we have shown ADAC in CD8+ populations to be Fas independent,
      TNF-alpha receptor 2 (TNFR2) mediated, caspase dependent, and accompanied by a
      decrease in Bcl-2. We now employ flow cytometry to follow ADAC within individual
      CD8+ cells to demonstrate that the intense TCR signal induced in high avidity CTL
      by supra-optimal antigen density results 8 - 16 h later in a caspase-independent
      TNFR2 down-modulation that is directly related to the stimulating APC antigen
      density and concludes in a rapid onset of apoptosis by 18 - 24 h. Individual CTL
      undergoing apoptosis exhibit a dramatic and concurrent: (1) positive staining
      with Annexin V and propidium iodide; (2) transformation to a smaller cell size
      characteristic of apoptosis; and (3) a nearly complete loss of Bcl-2, c-IAP1, and
      TRAF2. We conclude that the antigen-dependent apoptosis of CD8+ CTL occurs when a
      tandem TCR/TNFR2 signal initiates an abrupt and concordant onset of multiple
      apoptotic events.

PMID- 11592072
TI  - Influence of enterotoxin on mucosal intranet: selective inhibition of extrathymic
      T cell development in intestinal intraepithelial lymphocytes by oral exposure to
      heat-labile toxin.
AB  - We tested the possibility that heat-labile enterotoxin of Escherichia coli (LT)
      affects the development of extrathymic T cells in the intraepithelial lymphocyte
      (IEL) compartment. After oral administration of LT, the number of extrathymic
      CD8alphaalpha+ IEL was selectively and significantly diminished when compared
      with the corresponding cells in phosphate-buffered saline-fed control mice. To
      clarify the mechanism behind this selective reduction of CD8alphaalpha+ IEL, we
      analyzed the expression of essential cytokines and their corresponding receptors
      for the mucosal intranet formed by intestinal epithelial cells (IEC) and IEL. The
      expression levels of stem cell factor, interleukin (IL)-7, and IL-15 in IEC, and
      their corresponding receptors, i. e. c-kit, IL-7 receptor, and IL-15 receptor, in
      CD8alphaalpha+ IEL were reduced following oral feeding with LT. These findings
      suggest that LT negatively regulates development of CD8alphaalpha+ IEL via the
      disruption of mucosal intranet-associated cytokine and cytokine receptors, which
      are required for the development and/or expansion of extrathymically developed T
      cells. Further, LT-induced destruction of the mucosal intranet resulted in the
      impairment of IEC generation via an increase of apoptosis.

PMID- 11592073
TI  - Direct activation of dendritic cells by the malaria parasite, Plasmodium chabaudi
      chabaudi.
AB  - A primary infection of mice with Plasmodium chabaudi chabaudi (AS) is
      characterized by a rapid and marked inflammatory response. Typically, IL-12, TNF
      alpha and IFN-gamma are produced in the spleen, and are transiently present in
      plasma. The cells involved in this early response are unknown. Here we show that
      dendritic cells derived from GM-CSF-stimulated mouse bone marrow cultures produce
      TNF-alpha within 30 min of exposure to P.c.chabaudi schizonts. IL-6, IL-12p40 and
      p70 follow this. The production of these cytokines was not dependent on the
      presence of T cells or NK cells and did not require CD40. Incubation of dendritic
      cells with P.c.chabaudi schizonts also resulted in up-regulation of MHC class II,
      CD40 and CD86 but not CD80. In contrast to some strains of the human parasite, P.
      falciparum, P.c. chabaudi (AS) did not inhibit the up-regulation of MHC class II,
      CD86 or CD40 induced by LPS. Therefore, the erythrocytic stages of P.c.chabaudi
      are able to activate dendritic cells directly. The consequences of such an
      interaction could be rapid activation of TH1 cells and induction of immunity, and
      in the event of a large response also induction of TNF-alpha associated
      pathology.

PMID- 11592074
TI  - Regulation of ST2L expression on T helper (Th) type 2 cells.
AB  - T1/ST2L, an IL-1 receptor homologue, is selectively expressed on murine Th2 cells
      and specific anti-ST2L antibodies can profoundly modulate the Th1/Th2 balance in
      vivo. Naive CD4+ T cells do not express ST2L but do so on activation with
      specific antigen in the presence of IL-4 or when stimulated with low doses of
      antigen in the absence of exogenously added IL-4. Similarly enhanced ST2L
      expression occurred after stimulation of Th2 cells with antigen or the mitogen
      ConA in the presence of APC. Restimulation of Th2 cells in the presence of IFN
      gamma led to a decreased expression of ST2L to below basal levels. Conversely,
      Th2 cells cultured with IL-4 led to increased ST2L expression. The reduced
      expression of ST2L in response to high doses of antigen is also reversed by the
      neutralization of IFN-gamma. Using an ST2L promoter/luciferase reporter gene
      construct, we show that the distal but not proximal ST2L promoter is responsible
      for specific gene expression in Th2 cells. IL-4 enhances, whereas IFN-gamma
      suppresses ST2L expression via direct modulation of the distal promoter of the
      ST2L gene. These data provide a mechanistic explanation for the selective
      expression of ST2L on Th2 cells.

PMID- 11592075
TI  - Efficient assembly of recombinant major histocompatibility complex class I
      molecules with preformed disulfide bonds.
AB  - The expression of major histocompatibility class I (MHC-I) crucially depends upon
      the binding of appropriate peptides. MHC-I from natural sources are therefore
      always preoccupied with peptides complicating their purification and analysis.
      Here, we present an efficient solution to this problem. Recombinant MHC-I heavy
      chains were produced in Escherichia coli and subsequently purified under
      denaturing conditions. In contrast to common practice, the molecules were not
      reduced during the purification. The oxidized MHC-I heavy chain isoforms were
      highly active with respect to peptide binding. This suggests that de novo folding
      of denatured MHC-I molecules proceed efficiently if directed by preformed
      disulfide bond(s). Importantly, these molecules express serological epitopes and
      stain specific T cells; and they bind peptides specifically. Several denatured
      MHC-I heavy chains were analyzed and shown to be of a quality, which allowed
      quantitative analysis of peptide binding. The analysis of the specificity of the
      several hundred human MHC haplotypes, should benefit considerably from the
      availability of pre-oxidized recombinant MHC-I.

PMID- 11592076
TI  - Variant isoforms of CD44 are required in early thymocyte development.
AB  - The earliest T cells homing to the thymus (CD3-CD4loCD8-) express CD117 (c-kit),
      CD43 (leukosialin), and the integrins CD11a (alphaL), CD11b (alphaM), CD29
      (beta1), CD49f (alpha6), and CD44. Using reagents specific for CD44 variant
      isoforms (CD44v), we demonstrated that CD44v were expressed on virtually all
      early thymocytes,whereas cells carrying only the standard molecule (CD44s, not
      containing any variant domains), which is ubiquitously found on mature
      lymphocytes later, are very sparse. The expression of CD44v was closely
      correlated with CD43 and CD117 and was restricted to the CD3-CD4loCD8- stage.
      CD44v were detected on lymphocyte progenitor populations in the fetal blood,
      liver, thymus and spleen, as well as in the adult bone marrow. Functional studies
      demonstrated that only cells expressing CD44v from fetal liver and adult bone
      marrow could efficiently populate fetal thymic stroma and develop into mature T
      cells. In fetal thymic organ cultures anti-CD44v antibodies specifically blocked
      thymocyte development. We also present evidence that CD44v were required for the
      initial interaction of hematopoietic progenitor cells with the thymic stroma. Our
      data imply that CD44v are not only a useful marker for hematopoietic progenitors,
      but also play a functional role in the initiation of thymocyte development.

PMID- 11592077
TI  - Activation through CD40 ligation induces functional Fas ligand expression by
      Langerhans cells.
AB  - Langerhans cells (LC) are professional antigen-presenting cells of dendritic cell
      (DC) lineage and are critical for the induction of primary immune responses in
      skin. Following antigenic stimulation, LC migrate to regional lymph nodes and
      induce antigen-specific activation of T cells. After primary expansion, the
      majority of T cells undergo Fas/Fas ligand (FasL)-mediated apoptotic cell death,
      thereby suppressing their excessive expansion. Although recent investigations
      have indicated an immunoregulatory function for DC, whether LC could be involved
      in Fas/FasL-mediated suppression of activated T cells is still unclear. In this
      study, we found that LC express FasL after activation triggered through CD40
      molecules on their surface, but not by stimulation with LPS or IFN-gamma. The
      functional significance of FasL expression by LC was demonstrated using two
      different assays for apoptosis induced in Jurkat cells. The apoptosis in Jurkat
      cells was completely blocked by anti-FasL blocking antibody, suggesting a
      Fas/FasL-mediated mechanism. These results indicate a new feedback mechanism to
      down-regulate T cell activation by LC through the interaction of the TNF
      receptor/ligand superfamily, CD40/CD40L and Fas/FasL.

PMID- 11592078
TI  - Interleukin-2 enhances the natural killer cell response to Herceptin-coated
      Her2/neu-positive breast cancer cells.
AB  - The Her2/neu (c-erbB-2) oncogene encodes a 185-kDa protein tyrosine kinase which
      is overexpressed in 20% of breast adenocarcinomas and is recognized by a
      humanized anti-Her2/neu monoclonal antibody (mAb) (rhu4D5 or Herceptin). Natural
      killer (NK) cells are capable of mediating antibody-dependent cell cytotoxicity
      (ADCC) against antibody-coated targets via their expression of a low-affinity
      receptor for IgG (FcgammaRIII or CD16). NK cells can be expanded in cancer
      patients via the administration of low-dose interleukin-2 (IL-2) and become
      potent cytotoxic effectors following exposure to high doses of IL-2. We tested IL
      2-activated NK cells against Her2/neu+ (MCF-7Her2/neu) and Her2/neu- (MDA-468)
      breast cancer cell lines in a 4-h 51Cr-release cytotoxicity assay in the presence
      or absence of rhu4D5 mAb (effector : target ratio = 10 : 1). Specific lysis of
      rhu4D5-coated MCF-7Her2/neu and MDA-468 target cells by IL-2-activated NK cells
      was 35% and 3%, respectively (p < 0.05). Lysis was less than 5% when targets were
      treated with either the non-humanized mu4D5 mAb or control huIgG. Lysis of rhu4D5
      coated MCF-7Her2/neu cells was inhibited by 80 % when NK cells were pre-treated
      with an anti-Fc receptor antibody prior to use in the cytotoxicity assay.
      Enhanced ADCC of MCF-7Her2/neu target cells was seen when the effector cells
      consisted of mononuclear cells obtained from a patient demonstrating significant
      expansion of NK cells secondary to therapy with low-dose IL-2. Serum from
      patients receiving infusions of rhu4D5 mAb could substitute for exogenous
      antibody in the ADCC assay. NK cells activated by rhu4D5-coated tumor cells in
      the presence of IL-2 also produced large amounts of IFN-gamma with concomitant up
      regulation of cell-surface activation markers CD25 and CD69. These results lend
      support to the concurrent use of rhu4D5 mAb and IL-2 therapy in patients with
      cancers that express the Her2/neu oncogene.

PMID- 11592079
TI  - Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for
      plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high
      amounts of IL-12.
AB  - Human plasmacytoid dendritic cells (DC) (PDC, CD123+) and myeloid DC (MDC,
      CD11c+) may be able to discriminate between distinct classes of microbial
      molecules based on a different pattern of Toll-like receptor (TLR) expression.
      TLR1-TLR9 were examined in purified PDC and MDC. TLR9, which is critically
      involved in the recognition of CpG motifs in mice, was present in PDC but not in
      MDC. TLR4, which is required for the response to LPS, was selectively expressed
      on MDC. Consistent with TLR expression, PDC were susceptible to stimulation by
      CpG oligodeoxynucleotide (ODN) but not by LPS, while MDC responded to LPS but not
      to CpG ODN. In PDC, CpG ODN supported survival, activation (CD80, CD86, CD40, MHC
      class II), chemokine production (IL-8, IP-10) and maturation (CD83). CD40 ligand
      (CD40L) and CpG ODN synergized to activate PDC and to stimulate the production of
      IFN-alpha and IL-12 including bioactive IL-12 p70. Previous incubation of PDC
      with IL-3 decreased the amount of CpG-induced IFN-alpha and shifted the cytokine
      response in favor of IL-12. CpG ODN-activated PDC showed an increased ability to
      stimulate proliferation of naive allogeneic CD4 T cells, butTh1 polarization of
      developing T cells required simultaneous activation of PDC by CD40 ligation and
      CpG ODN. CpG ODN-stimulated PDC expressed CCR7, which mediates homing to lymph
      nodes. In conclusion, our studies reveal that IL-12 p70 production by PDC is
      under strict control of two signals, an adequate exogenous microbial stimulus
      such as CpG ODN, and CD40L provided endogenously by activated T cells. Thus, CpG
      ODN acts as an enhancer of T cell help, while T cell-controlled restriction to
      foreign antigens is maintained.

PMID- 11592080
TI  - Scheduled kinetics of cell proliferation and phenotypic changes during immature
      thymocyte generation.
AB  - Precursor CD4-CD8- (DN) thymocytes rearrange their TCR-beta genes, and only those
      which succeed in beta-selection subsequently expand and differentiate into
      immature CD4+CD8+ (DP) thymocytes. The cell subsets corresponding to the
      successive steps of this transition can be defined in terms of CD44 and CD25
      expression. We partially synchronized the differentiation process by eliminating
      cycling cells with the anti-mitotic agent demecolcine. Using in vivo pulse
      labeling with bromodeoxyuridine, we determined the order of entry into DNA
      synthesis of the different DN and transitory (CD4-/lo CD8+) cell subsets. Two
      independent proliferation phases were identified. The first cells to enter the
      cell cycle were CD44-CD25lo, and CD4/CD8/TCR-/BrdU four-color staining showed
      that they all expressed a low density of the TCR-beta chain, an element of the
      pre-TCR (the TCR-alpha locus is still in germ-line configuration at this stage).
      Cycling of CD44+CD25+ cells was detected later, and no starting point was
      observed at the CD44-CD25hi stage. CD8 expression was immediately detectable in
      cycling cells, but they took 24 h to reach the DP stage. The study of TCR-Calpha
      deficient mice showed that beta gene rearrangement occurred once proliferation
      had ceased at the DP stage, and that it had no influence on the DN-DP transition.
      These data show that precursor thymocytes undergo two independent waves of
      expansion, and that the second wave is restricted to cells capable of pre-TCR
      expression.

PMID- 11592081
TI  - NK cell functions restrain T cell responses during viral infections.
AB  - NK cell functions for regulation of T cell responses were evaluated during acute
      viral infections. In vivo depletion studies established that the presence of NK
      cells in murine cytomegalovirus (MCMV)-infected immunocompetent mice negatively
      affected CD4 and CD8 T cell IFN-gamma expression, bromodeoxyuridine (BrdU)
      incorporation, and expansion. To evaluate NK cell effects, under conditions when
      NK cells do not control viral replication, experiments were performed using
      lymphocytic choriomeningitis virus (LCMV). Depletion of NK cells did not affect
      LCMV-elicited T cell responses in immunocompetent mice; however, the presence of
      NK cells did inhibit CD4 T cell IFN-gamma production, BrdU incorporation, and
      expansion in infected MHC class I- and CD8 T cell-deficient beta2M-/- mice.
      Together, the results reveal a previously unappreciated immunoregulatory role of
      NK cells for downstream T cell responses.

PMID- 11592082
TI  - p38 MAP kinase activity modulates alpha beta T cell development.
AB  - Reciprocal interactions between bone marrow derived precursor cells and the
      thymic environment lead to the generation of the complete repertoire of diverse
      and functional T cells. We have previously shown that p38 MAP kinase is activated
      in response to intrathymic signals in thymocytes. In this report we provide
      evidence that p38 MAP kinase activity is essential for pre-TCR-mediated
      transition of thymocytes from the CD4- CD8- to the CD4+ CD8+ stage of
      development. In the absence of p38 MAP kinase activity differentiation of alpha
      beta T cells, but not gamma delta T cells, was blocked.

PMID- 11592083
TI  - Design of a polyepitope construct for the induction of HLA-A0201-restricted HIV 1
      specific CTL responses using HLA-A*0201 transgenic, H-2 class I KO mice.
AB  - HLA-A*0201 transgenic, H-2D(b)/mouse beta2-microglobulin double-knockout mice
      were used to compare and optimize the immunogenic potential of 17HIV 1
      derived,HLA-A0201-restricted epitopic peptides. A tyrosine substitution in
      position 1 of the epitopic peptides, which increases both their affinity for and
      their HLA-A0201 molecule stabilizing capacity, was introduced in a significant
      proportion, having verified that such modifications enhance their immunogenicity
      in respect of their natural antigenicity. Based on these results, a 13
      polyepitope construct was inserted in the pre-S2 segment of the hepatitis B
      middle glycoprotein and used for DNA immunization. Long-lasting CTL responses
      against most of the inserted epitopes could be elicited simultaneously in a
      single animal with cross-recognition in several cases of their most common
      natural variants.

PMID- 11592084
TI  - Distinct ligand binding properties of Mac-2-binding protein and mouse cyclophilin
      [correction of mousephilin] C-associated protein.
AB  - Human Mac-2-binding protein (Mac-2-BP) is a secreted glycoprotein that is widely
      expressed. It binds to the human macrophage-associated lectin Mac-2 and has been
      suggested to have a role in host defence. Mouse cyclophilin C-associated protein
      (mCyCAP) is also a secreted glycoprotein that binds with high affinity to
      cyclophilin C in the absence of the immunosuppressive drug cyclosporin A. The two
      proteins share a similar domain structure and considerable sequence identity,
      including a highly conserved scavenger receptor cysteine-rich domain, and both of
      them exert their function within the immune system. To elucidate whether these
      molecules are also functional homologues, we compared their ligand binding
      properties using cell lines which express Mac-2-BP or mCyCAP as well as
      transfected cell lines stably expressing mCyCAP or a mutant version lacking the
      scavenger domain. These experiments show that Mac-2-BP is unable to bind to
      either human or mouse cyclophilin C and thatmCyCAP cannot bind to Mac-2. The
      scavenger domain is not required for the interaction between mCyCAP and
      cyclophilin C. We conclude that these proteins may be part of a larger family of
      proteins of immunological importance in which closer functional homologues might
      exists.

PMID- 11592085
TI  - The role of ICAM-1 molecule in the migration of Langerhans cells in the skin and
      regional lymph node.
AB  - ICAM-1 (CD54) plays an important role in the cell-cell interaction and migration
      of leukocytes. Previous studies have shown that ICAM-1 is involved in
      inflammatory reactions and that a defect in ICAM-1 gene inhibits allergic contact
      hypersensitivity. This study indicates that the migration of hapten presenting
      Langerhans cells into the regional lymph nodes was significantly reduced in ICAM
      1-deficient mice compared to wild-type C57BL/6 mice. The reduced number of
      dendritic cells in regional lymph nodes did not result from abnormal migration of
      Langerhans cells into the skin of ICAM-1-deficient mice. The concentration and
      distribution of Langerhans cells in the naive skin of ICAM-1-deficient mice was
      equal to that of wild-type mice. Following hapten sensitization, Langerhans cell
      migration out of the skin and recruitment of fresh Langerhans cells back to the
      epidermis was not affected in ICAM-1-deficient mice. Further experiments
      demonstrated that ICAM-1 deficiency on lymphatic endothelium rather than on
      dendritic cells was responsible for the reduced migration of Langerhans cells
      into draining lymph nodes. This study indicates that ICAM-1 regulates the
      migration of dendritic cells into regional lymph nodes but not into or out of the
      skin.

PMID- 11592086
TI  - Analysis of the oligomeric requirement for signaling by CD40 using soluble
      multimeric forms of its ligand, CD154.
AB  - We describe the construction of a novel soluble dodecameric form of CD154 (CD40
      ligand) that is more effective than trimeric tCD154 in triggering B cell
      activation. Dodecameric surfactant protein (SP)-D-CD154 was more potent than
      tCD154 in inducing B cell proliferation over a wide range of concentrations. At
      saturating concentrations, the level of proliferation triggered by SP-D-CD154 was
      fourfold higher than that achieved with tCD154. Moreover, stimulation with
      dodecameric CD154 induced higher levels of the costimulatory molecules ICAM-1 and
      CD86. The higher activity of dodecameric CD154 when compared to trimeric CD154 is
      unlikely to be due to differences in their avidity for CD40, since both forms
      bound to CD40 strongly. Therefore, the extent of receptor clustering directly
      regulates signaling by CD40.

PMID- 11592087
TI  - Different requirements for alpha-galactosylceramide and recombinant IL-12
      antitumor activity in the treatment of C-26 colon carcinoma hepatic metastases.
AB  - The glycolipid alpha-galactosylceramide (alpha-GalCer), ligand of NKT cells, has
      been recently shown to induce antitumor immunity in mice through the induction of
      IL-12 production by dendritic cells. In the present study we compared alpha
      GalCer and rIL-12 antitumor activities in the treatment of hepatic metastases of
      the C-26 murine colon carcinoma. We show that in immunocompetent mice the two
      molecules display similar efficacy, whereas in mice knockout (KO) for beta2
      microglobulin (beta2m), IFN-gamma or IL-12p40, alpha-GalCer antitumor activity is
      severely impaired. Conversely,in all such KO mice, rIL-12 retains its efficacy.
      In this context, the IL-12 effect relies on NK cell function since it is
      abrogated by antibodies to NK1.1, expressed by both NK and NKT cells, but not in
      beta2m KO mice that lack NKT and CD8 T cells, but have a perfectly functional NK
      cell population. Furthermore, in IFN-gamma and IL-12p40 double KO mice, exogenous
      rIL-12 completely loses antitumor efficacy, suggesting the existence of an IFN
      gamma-independent IL-12 effect that does require the presence of endogenous IL
      12p40 chain.

PMID- 11592088
TI  - TGF-beta1 and donor dendritic cells are common key components in donor-specific
      blood transfusion and anti-class II heart graft enhancement, whereas tolerance
      induction also required inflammatory cytokines down-regulation.
AB  - Heart allograft tolerance in adult recipients can be induced in the LEW.1W to
      LEW.1A congeneic strain combination by pre-graft donor-specific blood transfusion
      (DST). Long-term survivors accept LEW.1W graft but reject third party skin
      grafts. As tolerant recipients of heart allografts showed an increase in anti
      donor class II antibodies, we hypothesize that these antibodies could be
      instrumental in tolerance induction. However, anti-donor MHC class II alone
      prolonged graft survival but did not induce heart allograft tolerance in this
      combination. We analyzed the immune response patterns in heart allograft
      recipients following the injection of anti-donor class II antibodies
      (prolongation) or DST priming (tolerance). As suggested by the different
      phenomena, several immunological patterns were strikingly different between the
      two models. In strong contrast to DST-tolerant recipients, at 5 days after
      transplantation, neither Th1/Th2 nor inflammatory cytokines were inhibited in
      recipients treated with anti-donor class II antibodies, in which only
      prolongation of graft survival was induced. Nevertheless, in both models,
      depletion of resident dendritic cells (DC) from donor hearts inhibited tolerance
      induction (DST) or shortened allograft survival (anti-donor class II antibodies).
      Moreover, TGF-beta1 was not down-regulated and administration of neutralizing
      anti-TGF-beta1 antibody, which inhibited tolerance induction (DST), also
      shortened allograft survival (anti-donor class II antibodies). These results
      suggest that, in these two MHC class II-restricted models, both TGF-beta1 and
      donor DC have a pivotal role in prolonging graft survival. However, in the days
      following transplantation, further inhibition of inflammatory cytokine
      production, particularly Th1 and macrophage-derived cytokines is required for
      tolerance induction.

PMID- 11592089
TI  - CD56bright cells differ in their KIR repertoire and cytotoxic features from
      CD56dim NK cells.
AB  - In this study we present new differential characteristics of NK cells expressing
      CD56 surface antigen in low (CD56dim) or high (CD56bright) density. In contrast
      to CD56bright NK cells CD56dim cells express killer cell immunoglobulin (Ig)-like
      receptors (KIR) such as CD158a, CD158b, and NKB1. However, c-type lectin-like
      receptors (KLR) CD94/NKG2 and CD161 are present on both subsets. The ability to
      form conjugates with susceptible targets is approximately twice as strongly
      pronounced in CD56dim vs. CD56bright NK cells. Last but not least, granules of
      CD56dim cells contain about tenfold more perforin and granzyme A enabling
      potentially more effective cytolysis compared to CD56bright NK cells. On the
      other hand, CD56bright NK cells are superior in producing the proinflammatory
      cytokines IFN-gamma (28.5% vs. 20.8%, p<0.05) and TNF-alpha (28% vs. 15.8%,
      p<0.001). The different NK cell populations retained their specific phenotype in
      vitro during culture in the presence of IL-2 contradicting that they simply
      display different stages of maturity. Taken together our data support the view
      that CD56bright cells are specialized NK cells that regulate immunological
      response mechanisms rather by cytokine supply than by their cytotoxic potential.
      The poor cytolytic capacity of CD56bright NK cells can be explained by weak
      ability in forming conjugates with target cells and low contents of perforin and
      granzyme A in their granules.

PMID- 11592090
TI  - Matrix metalloproteinases: a multifunctional group of molecules.
AB  - The matrix metalloproteinases are a large group of zinc-containing proteases with
      a central role in the degradation of all types of extracellular matrix. Increased
      matrix degradation is a characteristic feature of several disease processes, most
      notably tumour invasion; it is now widely recognized that this group of proteases
      has a key role in facilitating invasion and metastasis. However, it is also
      becoming increasingly recognized that the matrix metalloproteinases are a
      multifunctional group of biologically important molecules with diverse roles in
      normal cell growth, differentiation, and cell regulation, and with involvement in
      the early stages of tumourigenesis. Some of these regulatory functions may be
      distinct from the matrix-degrading capabilities of this group of enzymes.

PMID- 11592091
TI  - The androgen receptor gene and its influence on the development and progression
      of prostate cancer.
AB  - Prostate adenocarcinoma has the highest incidence of any malignancy and is the
      second leading cause of cancer-related deaths in men in industrialized countries.
      The development and progression of prostate cancer are dependent on testosterone
      and dihydrotestosterone; the androgen receptor is the vehicle through which these
      androgens exert their regulation on prostate cellular proliferation and
      differentiation. As a result, much effort has been devoted to elucidating the
      role of the androgen receptor in prostate cancer. The CAG and GGN trinucleotide
      repeats in exon 1 of the androgen receptor gene have been linked to prostate
      cancer risk and progression in some studies. Also, androgen receptor gene
      amplification may be a mechanism of prostate cancer cell adaptation to hormonal
      therapy. In addition, androgen receptor somatic mutations can result in receptors
      that have altered binding specificity when compared with wild-type receptors and
      heightened affinity for hormones other than testosterone and dihydrotestosterone.
      Gene amplification and somatic mutations, coupled with the fact that various
      growth factors have been shown to stimulate androgen receptor activity
      independently of androgens, may enable prostate cancer cells to grow despite
      testicular-androgen ablation. Unfortunately, current medical therapy for
      metastatic prostate cancer is deficient, hormone-refractory prostate cancer is a
      major obstacle in treatment, and, as a result, prostate cancer mortality is still
      significant. Further study of the function of the androgen receptor will offer a
      better understanding of prostate cancer pathogenesis and progression, aiding the
      development of more effective treatments for this disease.

PMID- 11592093
TI  - MnSOD expression is less frequent in tumour cells of invasive breast carcinomas
      than in in situ carcinomas or non-neoplastic breast epithelial cells.
AB  - Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme capable of
      neutralizing superoxide anion molecules. In previous studies it has been
      suggested to suppress both tumour proliferation and apoptosis. This study
      investigated 65 invasive, 50 in situ and 19 benign hyperplastic breast lesions
      for its immunohistochemical expression. MnSOD expression was also tested with in
      situ hybridization. To study cell proliferation, apoptosis and their association
      with MnSOD expression the neoplastic breast lesions were immunostained with a
      monoclonal antibody to Ki-67 and the extent of apoptosis in them was determined
      by the TUNEL method. 32/65 (49%) of the invasive ductal carcinomas, 41/50 (82%)
      of the in situ and 15/19 (79%) of the benign hyperplasias expressed the MnSOD
      protein. There were significantly more MnSOD positive cases in in situ carcinoma
      and in benign hyperplasia than in invasive carcinoma (p=0.00016 and p=0.022,
      respectively). Positivity was also more frequently found in non-neoplastic ductal
      and acinar epithelial cells than in invasive carcinoma. On the other hand,
      neoplastic epithelial cells of invasive and in situ carcinoma showed strong
      positivity more often than the epithelial cells of benign hyperplasia or non
      neoplastic epithelium. In breast lesions, MnSOD positivity did not associate with
      proliferation or apoptosis. The lower frequency of MnSOD positive cases in
      invasive breast carcinoma suggests that the lack of its expression might
      contribute to the development of an invasive breast carcinoma phenotype and that
      it could in this way operate as a tumour suppressor gene, as previously
      suggested.

PMID- 11592092
TI  - MMP-19: cellular localization of a novel metalloproteinase within normal breast
      tissue and mammary gland tumours.
AB  - Matrix metalloproteinases (MMPs) are instrumental in promoting and facilitating
      the spread of malignant diseases and in the de novo formation of blood vessels.
      This study has mapped the immunoreactivity of a novel, angiogenesis-related
      metalloproteinase--MMP-19--in normal breast tissue and in benign and malignant
      breast lesions and compared this pattern of expression with that of MMP-2. In the
      normal resting mammary gland, MMP-19 was strongly expressed in the myoepithelial
      layer of the ductal system; the alveolar and ductal epithelia displayed
      considerable, but lobule-specific, variations in labelling intensity. MMP-19 was
      also present within the smooth muscle and endothelial layers of large and medium
      sized blood vessels, as well as within capillary walls. In benign lesions, all
      tumour cells and their surrounding vasculature were uniformly and strongly
      immunoreactive for MMP-19. Progression towards an invasive phenotype and
      neoplastic dedifferentiation led to the disappearance of MMP-19 from tumour cells
      and blood vessels and a concomitant rise in the levels of MMP-2. In vitro
      experiments conducted with isolated smooth muscle cells cultivated on a solid
      substratum, or within the interstices of a collagen matrix, indicated that the
      expression of MMP-19 is influenced by the architecture of the surrounding
      extracellular matrix.

PMID- 11592094
TI  - Expression of the p53 homologues p63 and p73 in multiple simultaneous gastric
      cancer.
AB  - The tumour-suppressor protein p53 has recently been shown to belong to a family
      that includes two structurally related proteins, p63 and p73. This study
      investigated the status of p53 and its two homologues in multiple simultaneous
      gastric carcinomas. Expression and mutation of p53, p73 and p63 including the two
      major isotypes TAp63 and black triangleNp63, were examined by direct DNA
      sequencing, in situ hybridization, western blotting and immunohistochemistry in
      68 gastric carcinomas of 32 patients. The results obtained were correlated with
      pathohistological stage (according to UICC(16)) and several other
      histopathological factors and finally with patient survival. p53 mutations were
      detected in 23/68 carcinomas (34%) from 18 patients with a discordant mutation
      pattern. Independently of p53 mutation status, p73 transcripts and protein
      expression were found in 33/68 carcinomas from 24 patients. p63 positivity was
      found in 21 patients; 25 out of 68 tumours expressed p63. The number of cells
      containing p63 and their distribution depend on the degree of tumour
      differentiation. High grade carcinomas of the diffuse type exhibited a
      significantly higher p63 expression. In intestinal metaplasia and atrophic
      gastritis, an increase of TAp63 and black triangleNp63 staining was also
      observed. Specific mutations of p73 or p63 causing amino acid substitutions were
      not identified. Neither p53, p73 nor p63 were related to prognosis. p73 and p63
      have rarely been found to be mutated in gastric carcinomas, but both proteins
      were expressed in only a subset of tumours. The status of these p53 homologues
      was discordant in all patients with multiple simultaneous gastric carcinomas. The
      increased expression of p63 (TAp63 and black triangleNp63) in less well
      differentiated gastric carcinomas may indicate that p63 can act to promote
      neoplastic growth in the gastric epithelium.

PMID- 11592095
TI  - Mechanisms of oncogenesis in colon versus rectal cancer.
AB  - Observations support the theory that development of left- and right-sided
      colorectal cancers may involve different mechanisms. This study investigated
      different genes involved in oncogenesis of colon and rectal cancers and analysed
      their prognostic value. The study group comprised 35 colon and 42 rectal cancers.
      Rectal cancer patients had been treated with standardized surgery performed by an
      experienced rectal cancer surgeon. Mutation analysis was performed for p53 in
      eight colon cancers and for APC and p53 in 22 rectal cancers. MLH1, MSH2, Bcl-2,
      p53, E-cadherin and beta-catenin were investigated by immunohistochemistry in all
      colorectal tumours. APC mutation analysis of the MCR showed truncating mutations
      in 18 of 22 rectal tumours (82%), but the presence of an APC mutation was not
      related to nuclear beta-catenin expression (p=0.75). Rectal cancers showed
      significantly more nuclear beta-catenin than colon cancers (65% versus 40%,
      p=0.04). p53 mutation analysis corresponded well with p53 immunohistochemistry
      (p<0.001). Rectal cancers showed significantly more immunohistochemical
      expression of p53 than colon cancers (64% versus 29%, p=0.003). In rectal
      cancers, a significant correlation was found between positive p53 expression and
      worse disease-free survival (p=0.008), but not in colon cancers. Cox regression
      showed that p53-expression (p=0.03) was an independent predictor for disease-free
      survival in rectal cancers. This study concluded that rectal cancer may involve
      more nuclear beta-catenin in the APC/beta-catenin pathway than colon cancer
      and/or nuclear beta-catenin may have another role in rectal cancer independently
      of APC. The p53-pathway seems to be more important in rectal cancer, in which it
      also has independent prognostic value. When prognostic markers are investigated
      in larger series, differences in biological behaviour between colon and rectal
      cancer should be considered.

PMID- 11592096
TI  - Quantitative analysis of IL-10 and IFN-gamma mRNA levels in normal cervix and
      human papillomavirus type 16 associated cervical precancer.
AB  - Human papillomavirus type 16 is a major factor in cervical carcinogenesis.
      Inappropriate cytokine synthesis may direct the local immune response away from a
      type-1 (cellular) pattern and may subsequently contribute to the development and
      progression of precancer. Quantitative reverse transcription-polymerase chain
      reaction (RT-PCR) using a competitive mimic was carried out to determine type-1
      (interferon gamma (IFN-gamma)) and type-2 (interleukin-10 (IL-10)) cytokine mRNA
      levels in whole cervical specimens (without microdissection) from seven normal
      and nine HPV-16 positive CIN formalin-fixed paraffin-embedded tissues.
      Microdissection was used to measure separately the epithelial and sub-epithelial
      levels of IFN-gamma and IL-10 mRNAs in 11 specimens of normal cervix and 25 HPV
      16 positive CIN (nine CIN 1, seven CIN 2 and nine CIN 3). IFN-gamma mRNA was
      lower in CIN than normal (p=0.04). IL-10 mRNA level in CIN was significantly
      higher (p=0.005) than in normal cervix (before microdissection). Epithelial IFN
      gamma mRNA showed a significant decrease in all grades of CIN (median=3.58)
      compared with normal (7.74) (p<0.05), but there was no significant difference
      between the grades. A significant decrease in sub-epithelial IFN-gamma mRNA was
      found in CIN 1(9.81), CIN 2 (3.82) and CIN 3 (4.62) compared with normal cervix
      (27.35) (p<0.05). Also, sub-epithelial IFN-gamma mRNA was significantly lower in
      CIN 2 and CIN 3 than in CIN 1 (p=0.005 and 0.0005, respectively). IL-10 was
      detected in the epithelium of only one of 11 normal and one of 25 CIN, but sub
      epithelial IL-10 was significantly higher in CIN 2 (0.08) and CIN 3 (0.26) than
      in normal (0.00) (p=0.036 and 0.0032, respectively). There was no significant
      difference in the sub-epithelial level of IL-10 between normal and CIN 1 (0.00)
      (p=0.96). Our results suggest that reduced epithelial and sub-epithelial IFN
      gamma, as well as increased sub-epithelial IL-10 synthesis may play a role in the
      development and progression of HPV-16 associated cervical precancer.

PMID- 11592097
TI  - mRNA markers of breast cancer nodal metastases: comparison between mammaglobin
      and carcinoembryonic antigen in 248 patients.
AB  - Histological detection of axillary lymph node metastases is still the most
      valuable prognostic parameter for breast cancer, but about 30% of node-negative
      patients relapse within five years, suggesting that current methods are
      inadequate for identifying metastatic disease. More sensitive, PCR-based methods
      for the detection of metastatic cells are now available, enabling the
      amplification of cancer cell-specific mRNA messages by the RT-PCR assay. An ideal
      tumour marker, consistently expressed in tumour samples and not at all in normal
      lymph nodes, remains to be identified. The present study first investigated the
      expression of seven mRNA markers, CEA, CK19, c-Met, mammaglobin, MUC-1, beta1-
      >GalNAc-T and p97, selected on the basis of their previously reported specificity
      for breast cancer cells. Eighteen lymph nodes were examined from patients without
      tumours. Only mammaglobin mRNA and CEA mRNA were not expressed in normal nodes.
      All of the other markers showed a band of expression in 17%-55% of cases,
      indicating that they are not breast cancer-specific. CEA mRNA and mammaglobin
      mRNA expression could be detected in 15/20 (75%) and 19/20 (95%) primary breast
      carcinomas, respectively. The expression of mammaglobin mRNA and CEA mRNA was
      then compared in axillary lymph nodes from 248 consecutive breast cancer
      patients, 89 with histologically documented lymph node metastasis and 159 without
      histological evidence of metastatic disease. Ninety-seven per cent of the
      patients with histologically involved nodes showed expression of mammaglobin
      mRNA, whereas CEA mRNA was expressed in 79% of these cases. In the group of
      patients with histologically negative lymph nodes, 46 (29%) and 32 (20%) were
      found to be positive for mammaglobin and CEA expression, respectively, indicating
      the presence of metastases not detected by routine histological examination of
      one lymph node section. These results show that both mammaglobin RT-PCR and CEA
      RT-PCR are useful tools for the detection of breast cancer metastases in axillary
      lymph nodes. The detection sensitivity of the mammaglobin RT-PCR is far superior
      to that of the CEA RT-PCR, allowing the diagnosis of occult metastases in nearly
      one-third of cases.

PMID- 11592098
TI  - The pattern of expression of the microtubule-binding protein RHAMM/IHABP in
      mammary carcinoma suggests a role in the invasive behaviour of tumour cells.
AB  - Intracellular hyaluronic acid binding protein (RHAMM/IHABP), which was recently
      identified as a novel member of the microtubule-associated protein (MAP) family,
      has the capacity to interact not only with microtubules but also with
      microfilaments. The molecule, which is known to be expressed in mammary carcinoma
      cells, might, through virtue of its intracellular interactions, influence tumour
      cell morphology and motility. This possibility was examined in a series of 189
      mammary carcinomas by immunohistochemistry, using a polyclonal antibody to
      RHAMM/IHABP. Tumours were selected to include approximately equal numbers of
      consecutive grade I, II and III ductal carcinomas and invasive lobular
      carcinomas. Higher grade tumours had significantly lower expression of
      RHAMM/IHABP in the cytoplasm (p=0.02), but significantly increased expression in
      trabeculae (p=0.002) and further enhancement at the tumour island edges
      (p=0.002). Tumours of infiltrating lobular type had stronger expression in the
      overall cytoplasm (p=0.02) and trabeculae (p=0.08) than carcinomas of ductal
      type. The presence of strong trabecular expression was associated with a reduced
      overall survival time (p=0.017). These results suggest that RHAMM/IHABP
      expression may contribute to the motility and invasiveness of a tumour cell sub
      population in breast cancers.

PMID- 11592099
TI  - Laminin alpha2 chain (merosin M chain) distribution and VEGF, FGF(2), and
      TGFbeta1 gene expression in angiogenesis of supraglottic, lung, and breast
      carcinomas.
AB  - The prognostic significance of vessel quantification in human solid tumours is
      still debated, due to the presence of multiple factors modulating neoangiogenesis
      and the invasiveness of neoplastic cells. This study examined ten supraglottic
      squamous carcinomas, ten non-small cell lung carcinomas (three squamous, five
      bronchioloalveolar, two adenocarcinomas), and nine classic (NOS) invasive ductal
      breast carcinomas. The properties studied in these tumours were vascularity; the
      immunohistochemical distribution of adhesion molecules such as alpha2beta1,
      alpha3beta1, alpha4beta1, alpha5beta1, alpha6beta4, and ICAM-1 in endothelial
      cells; extracellular matrix proteins (ECMPs) and laminin alpha2 chain (merosin M
      chain) in basal membranes of vessels; and gene expression of vascular endothelial
      growth factor (VEGF), basic fibroblast growth factor (FGF2), and transforming
      growth factor beta1 (TGFbeta1), by in situ hybridization. Independently of tumour
      type and vascularity, laminin alpha2 chain expression was observed in the basal
      membranes of a limited proportion of vessels. In vitro experiments demonstrated
      laminin alpha2 chain expression mainly in early endothelial cell cultures,
      suggesting that laminin alpha2 chain expression in vivo can be considered a
      marker of early angiogenesis. Stromal and parenchymal vascularity was associated
      with laminin alpha2 chain expression in supraglottic carcinomas, whereas in the
      other tumours, laminin alpha2 chain-positive vessels were observed only in the
      stroma. In supraglottic carcinomas, VEGF-positive cells were mainly represented
      by neoplastic cells, whereas in the other tumours, the great majority of VEGF
      positive cells were macrophages and fibroblasts. FGF2- and TGFbeta1-positive
      cells were macrophages and fibroblasts in all tumours. These observations suggest
      that in addition to the quantification and distribution of vessels, evaluation of
      their maturation may contribute to a better understanding of the role of
      angiogenesis in the growth and spread potential of solid tumours. In this regard,
      in supraglottic carcinomas, parenchymal angiogenesis seems to be regulated mainly
      by neoplastic cells, which may help to explain their high metastatic potential;
      in solid tumours of different histogenesis, different cells might be responsible
      for modulating tumour angiogenesis.

PMID- 11592100
TI  - hTERT expression in sporadic renal cell carcinomas.
AB  - Human telomerase is a specialized reverse transcriptase that catalyses telomeric
      repeat addition at the ends of chromosomes. Activation of this enzyme is one of
      the key steps in cell immortalization and carcinogenesis, and one of its
      components, hTERT, is considered as the rate-limiting factor. While telomerase
      activity was found to be prognostically relevant in various cancers, results
      obtained from renal cell carcinomas (RCC) failed to show any correlation with the
      usual prognostic factors. The aim of the study was to reassess the role of
      telomerase and its hTERT component in the biological behaviour of RCC using new
      quantitative techniques, such as the quantitative evaluation of hTERT mRNA level
      by a real-time RT-PCR procedure and the measuring of telomerase activity by an
      ELISA TRAP assay. Since experimental evidence supports a relationship between
      cell proliferation or c-myc expression and telomerase, the proliferation index
      and c-myc mRNA levels were also studied. Forty-one RCC (29 conventional renal
      cell carcinomas (CRCC), 10 papillary RCC and two urothelial carcinomas) were
      studied. In 73% of cases, normalized hTERT mRNA expression was significantly
      higher in the tumour sample than in the normal tissue. Telomerase activity was
      detected in 63% of RCC, while corresponding normal tissue was always negative.
      Analysis of correlations showed firstly that both telomerase activity and hTERT
      mRNA level were lower in the group of CRCC versus non-CRCC (TRAP: 0.3+/-0.1
      versus 0.6+/-0.2, p<0.05; hTERT/PO mRNA: 5+/-3 versus 37+/-8, p<0.001,
      respectively); secondly, that in the group of CRCC, hTERT mRNA expression level
      was correlated with the stage of the tumour (p=0.01); and thirdly, that no
      correlation was observed between c-myc mRNA level and hTERT mRNA level. In
      conclusion, these results support the involvement of telomerase in RCC and the
      potential interest of hTERT mRNA quantification.

PMID- 11592101
TI  - Adamantinoma-like Ewing's sarcoma and Ewing's-like adamantinoma. The t(11; 22),
      t(21; 22) status.
AB  - Adamantinoma of the long bones and Ewing's sarcoma are two malignant tumours
      between which, at first sight, there seems to be no morphological and clinical
      relationship. Both tumours, however, are known to express cytokeratins.
      Adamantinoma is a tumour of true epithelial nature, predominantly expressing
      cytokeratins 14 and 19. Ewing's sarcoma, believed to be from neuroectodermal
      origin, like other mesenchymal tumours, can aberrantly express cytokeratin 8 and
      18. In the literature there are some reports of tumours showing clinical and/or
      morphological overlap between adamantinoma and Ewing's sarcoma, suggesting a
      possible relationship. These studies are mostly based on the epithelioid
      configuration of these lesions and their cytokeratin expression on
      immunohistochemistry. This raises the question of whether there is occasionally a
      morphological similarity between adamantinoma and Ewing's sarcoma, or whether
      there is a common genetic background. The Ewing's sarcoma/primitive peripheral
      neuroectodermal tumour (PNET) family is characterized in 90-95% of cases by a
      t(11; 22) and in 5-10% of cases by t(21; 22). In the few reports in the
      literature on cytogenetic investigations on adamantinoma, these translocations
      were never found using classical karyotyping. This study investigated the
      putative presence of t(11; 22) and t(21; 22) in 14 cases of adamantinoma by RT
      PCR. These translocations were not found in any of these cases. The results
      support the view that these tumours are genetically and clinically distinct, but
      may eventually show overlapping morphological and immunohistochemical features.

PMID- 11592102
TI  - beta-catenin nuclear expression correlates with cyclin D1 overexpression in
      sporadic desmoid tumours.
AB  - The immunohistochemical expression of beta-catenin, cyclin D1, Ki-67 and PCNA was
      Examined in 38 cases of sporadic extra-abdominal or abdominal-wall desmoid
      tumours without familial adenomatous polyposis (FAP), to evaluate the hypothesis
      that the accumulated beta-catenin within the nuclei could affect the regulation
      of the cyclin D1 gene. There was a statistically significant correlation between
      beta-catenin accumulation and cyclin D1 overexpression (p=0.029). Each group with
      beta-catenin accumulation or cyclin D1 overexpression showed a higher PCNA-LI
      than those without, the difference being statistically significant (p=0.007,
      p=0.004, respectively). Differential PCR was also performed to detect
      amplification of the cyclin D1 gene and mutational analysis was undertaken for
      exon 3 of the beta-catenin gene. Amplification of the cyclin D1 gene was observed
      in 13 out of 22 cases (59.1%). There were nine-point mutations in 7 out of 18
      cases (38.9%). The distribution of beta-catenin mutation fell within a wide
      range, from codon 21 to codon 67. In conclusion, beta-catenin nuclear expression
      correlated with cyclin D1 overexpression in sporadic desmoid tumours, which could
      be an in vivo model system for the APC-beta-catenin-Tcf pathway. In addition,
      beta-catenin mutations in desmoid tumours occurred at an unusually wide range of
      sites within the gene.

PMID- 11592103
TI  - Bone marrow contributes to renal parenchymal turnover and regeneration.
AB  - In order to establish whether extra-renal cells contribute to the turnover and
      repair of renal tissues, this study examined kidneys of female mice that had
      received a male bone marrow transplant and kidney biopsies from male patients who
      had received kidney transplants from female donors. By using in situ
      hybridization to detect Y-chromosomes it could be demonstrated that circulating
      stem cells frequently engraft into the kidney and differentiate into renal
      parenchymal cells. In the human renal grafts it was confirmed that some of the
      recipient-derived cells within the kidney exhibited a tubular epithelial
      phenotype, by combining in situ hybridization with immunostaining for the
      epithelial markers CAM 5.2 and the lectin Ulex europaeus. Female mouse recipients
      of male bone marrow grafts showed co-localization of Y-chromosomes and tubular
      epithelial markers Ricinus communis and Lens culinaris, and a specific cytochrome
      P450 enzyme (CYP1A2) indicating an appropriate functional capability of clustered
      newly formed marrow-derived tubular epithelial cells. Y-chromosome-containing
      cells were observed within glomeruli, with morphology and location appropriate
      for podocytes. Within the murine kidney, these Y-chromosome-positive cells were
      negative for the mouse macrophage marker F4/80 antigen and leukocyte common
      antigen, but were vimentin-positive. The presence of bone marrow-derived cells
      was noted in both histologically normal mouse kidneys and in human transplanted
      kidneys suffering damage from a variety of causes. These data indicate that bone
      marrow cells contribute to both normal turnover of renal epithelia and
      regeneration after damage, and it is suggested that this could be exploited
      therapeutically.

PMID- 11592104
TI  - Plasminogen activator inhibitor-1 as a measure of vascular remodelling in breast
      cancer.
AB  - The generation of urokinase plasminogen activator (uPA) by tumours is an
      important pathway for neoplastic cell invasion and metastasis. Indeed in several
      tumour types, elevated levels of uPA, its receptor (uPAR) or its inhibitor
      plasminogen activator inhibitor-1 (PAI-1) is associated with a poorer prognosis.
      Since endothelial cells also use this proteolytic system to remodel the
      extracellular matrix during angiogenesis and since angiogenesis, as assessed by
      microvessel density, is also a predictor of patient survival, this study was
      designed to investigate the relationship between angiogenesis and the urokinase
      system in breast tumours. The aims were to assess whether the uPA, uPAR and/or
      PAI-1 correlates with angiogenic activity and could therefore be a useful
      objective clinical measure of tumour neovascularization; and to clarify whether
      the poor outcome associated with high levels of the urokinase system is due to
      its association with angiogenesis. The study also sought to examine the
      relationship between the uPA system and vessel remodelling using loss of a
      basement membrane epitope (LH39) normally associated with established
      capillaries. The cytosolic levels of uPA, PAI-1 and uPAR were therefore measured
      by enzyme linked immunoabsorbent assay, together with tumour vascularity, in 136
      well-characterized invasive breast carcinomas. There were significant
      relationships between uPA and uPAR (Spearman r=0.37, p<0.0001), uPA and PAI-1
      (Spearman r=0.19, p=0.03) and between uPAR and PAI-1 (Spearman r=0.23 p=0.01). A
      significant correlation was also observed between PAI-1 and vessel remodelling
      (Spearman r=0.34, p=0.04), patient age (p=0.01), nodal status (p=0.047) and
      tumour grade (p=0.04), but no association between tumour vascularity and PAI
      (p=0.96), uPA (p=0.69) or uPAR (p=0.81) was present. No significant association
      was seen between any of the urokinase variables and expression of the angiogenic
      factor thymidine phosphorylase. Furthermore, no significant associations were
      found between any of the studied parameters and overall survival in a univariate
      analysis of the cancer patients. A multivariate Cox proportional hazard model of
      overall survival showed that uPA (p=0.15), but not uPAR (p=0.52) or PAI-1
      (p=0.61), gave no additional prognostic information. These findings show that uPA
      may work via an independent pathway to angiogenesis and therefore combined
      blockade of uPA and angiogenesis may have additional therapeutic benefits. It
      also shows, as recently demonstrated in animal models, that PAI-1 may be a key
      regulator of vascular remodelling in human cancer.

PMID- 11592105
TI  - Oxidative modifications of LDL increase its binding to extracellular matrix from
      human aortic intima: influence of lesion development, lipoprotein lipase and
      calcium.
AB  - Retention of atherogenic lipoproteins in the arterial intima by extracellular
      matrix (ECM) is assumed to occur during early atherogenesis and its further
      development. Low density lipoprotein (LDL) trapped in the intima may undergo
      oxidative modifications, which initiate a chain reaction in atherogenesis.
      Lipoprotein lipase (LPL) has been found to mediate the binding of native and
      oxidized LDL to ECM produced by cultured cells and to contribute to foam cell
      formation by mildly oxidized LDL. In this study ECM, isolated from human aortic
      intima with different atherosclerotic lesions, was used for the first time to
      measure the binding to it in vitro of native and differently oxidized 125I-LDL.
      Oxidation of 125I-LDL increased its binding to the ECM, which was most prominent
      with the material isolated from intima at the early stage of atherogenesis. With
      the progression of atherosclerosis, the ability of the isolated intimal ECM to
      bind native and oxidized 125I-LDL decreased, and strongly oxidized 125I-LDL
      decreased more than native and moderately oxidized 125I-LDL. LPL increased the
      binding of moderately oxidized 125I-LDL to the ECM more than native 125I-LDL,
      while it had only a small effect on strongly oxidized 125I-LDL. LPL-mediated
      binding of native and oxidized 125I-LDL decreased with the development of
      atherosclerotic lesions. Calcium ions also increased the binding of LDL to the
      ECM. This enhanced binding increased with the extent of LDL oxidation, especially
      at the early stage of atherogenesis, and decreased with lesion progression. These
      data suggest that the ability of ECM to retain LDL in arterial intima depends on
      LDL oxidation status and changes with the progression of atherogenesis. In
      addition, LPL and calcium ions may participate in the retention of LDL in vivo.

PMID- 11592106
TI  - Upregulation of tenascin and TGFbeta production in a type II alveolar epithelial
      cell line by antibody against a pulmonary auto-antigen.
AB  - Type II alveolar epithelial cells express a 70-90 kDa antigen to which
      circulating auto-antibodies have been previously identified in patients with
      cryptogenic fibrosing alveolitis (CFA). In vitro experiments have been conducted
      with a rabbit polyclonal antibody raised to this auto-antigen, and the type II
      epithelial cell line A549. This study examined possible effects that interaction
      of this antibody with type II epithelial cells might have on the production of
      cytokines and extracellular matrix components that may be important in the
      pathogenesis of CFA. There was a significant increase in TGFbeta and tenascin,
      but not IL4, production by the A549 cells after culture with the immune serum.
      Further experiments showed that after 72 hours in culture, the antibody decreased
      A549 cell number in a complement-dependent process, which appeared to be
      cytostatic rather than cytolytic. These results indicate in vitro biological
      activity for this antibody and suggest a possible in vivo role for auto-antibody
      to type II epithelial cells in the pathogenesis of CFA.

PMID- 11592107
TI  - Spontaneous plaque rupture and secondary thrombosis in apolipoprotein E-deficient
      and LDL receptor-deficient mice.
AB  - Apolipoprotein E-deficient (apoE(-/-)) and LDL receptor-deficient (LDLR(-/-))
      mice develop extensive atherosclerosis, but the occurrence of spontaneous plaque
      rupture and secondary thrombosis in these models has not been established. The
      goal of this study was to provide histological evidence of acute complications of
      atherosclerotic lesions in these mice and to assess their prevalence.
      Complications of atherosclerosis were initially studied in aortas of control mice
      which died during previous intervention studies. Coronary arteries and the aortic
      origin were then systematically assessed in serial sections through the heart of
      apoE(-/-) and LDLR(-/-) mice. Aortic plaque rupture and/or thrombi were seen in 3
      of 82 untreated mice from past intervention studies. Screening of heart sections
      of 33 older apoE(-/-) mice (age 9-20 months) showed extensive atherosclerosis in
      one or more coronary arteries of 18 animals. In three coronary arteries, the
      presence of blood-filled channels within advanced atherosclerotic lesions
      suggested previous plaque disruption/thrombotic events followed by
      recanalization. In the aortic origin of the same mice, four deep plaque ruptures
      (or erosions reaching necrotic core areas) and a large thrombus originating from
      the core of a disrupted atherosclerotic lesion were observed. Although plaque
      ruptures/deep erosions were far less frequent than in human populations, these
      observations demonstrate that spontaneous plaque rupture and secondary thrombosis
      do occur in apoE(-/-) and LDLR(-/-) mice. These mice may therefore be suitable
      for studying factors contributing to thrombotic complications of atherosclerosis.
      However, the frequent absence of a clearly defined single fibrous cap in murine
      coronary lesions limits their usefulness as a model of fibrous cap rupture.

PMID- 11592108
TI  - Copper-associated liver disease in North Ronaldsay sheep: a possible animal model
      for non-Wilsonian hepatic copper toxicosis of infancy and childhood.
AB  - Indian childhood cirrhosis (ICC), endemic Tyrolean infantile cirrhosis (ETIC) and
      idiopathic copper toxicosis (ICT), are clinically and pathologically
      indistinguishable liver disorders of infants and young children linked with
      exogenous copper and with increasing evidence for a genetic predisposition. North
      Ronaldsay sheep are a primitive breed which have adapted to a copper impoverished
      environment (<5 ppm) and display an abnormal sensitivity to copper poisoning when
      transferred to a copper replete (11 ppm) habitat. The aetiological parallels
      prompted a study of copper-associated liver disease in North Ronaldsay sheep
      (RCT) to see if the pathology could contribute to the understanding of the
      childhood disorder. A retrospective study was performed in which the livers of 22
      mainland-bred North Ronaldsay sheep were compared with three island-bred sheep
      and categorized for liver copper content and pathomorphology. It was found that
      all the mainland sheep had accumulated liver copper (>300 microg/g), in contrast
      to the island sheep, although 10 sheep with increased liver copper (mean 600 SD
      270 microg/g) showed no evidence of liver damage. A further 10 sheep with liver
      copper (mean 1276 SD 508 microg/g) exhibited periportal to panlobular
      histochemical copper retention, a periportal and/or panlobular pericellular
      fibrosis, a mixed inflammatory infiltrate and cholangioplasia. Steatosis was
      absent and regeneration was in abeyance. Finally, two sheep (liver copper >2000
      microg/g) had a more active hepatitis with a florid pericellular, panlobular
      fibrosis and cirrhosis. Electron microscopy identified large numbers of collagen
      producing hepatic stellate (Ito) cells in periportal regions. The pathological
      findings were sufficiently reminiscent of ICC, ETIC and ICT to warrant further
      exploration of RCT as a putative animal model. The North Ronaldsay sheep liver
      may be a useful tool for the investigation of copper-induced fibrogenesis.

PMID- 11592109
TI  - Potential roles for tumor necrosis factor and nuclear factor-kappaB in seizure
      activity.

PMID- 11592110
TI  - Lovastatin treatment decreases mononuclear cell infiltration into the CNS of
      Lewis rats with experimental allergic encephalomyelitis.
AB  - Mononuclear cell infiltration into the CNS and induction of inflammatory
      cytokines and iNOS in diseases like multiple sclerosis (MS) and experimental
      allergic encephalomyelitis (EAE) have been implicated in subsequent disease
      pathogenesis and progression. We report that Lovastatin treatment blocks the
      clinical disease and induction of inflammatory cytokines and iNOS in spinal cords
      of MBP induced EAE rats. A significant number of the infiltrating cells in CNS
      were ED1+ cells of monocyte/macrophage lineage. To understand the mechanism of
      efficacy of Lovastatin against EAE, we examined the effect of Lovastatin on the
      transmigration of mononuclear cells into EAE spinal cord. The data presented here
      documents that Lovastatin treatment attenuates the transmigration of mononuclear
      cells possibly by down regulating the expression of LFA-1, a ligand for ICAM, in
      endothelial-leukocyte interaction. These results indicate that Lovastatin
      treatment prevents infiltration by mononuclear cells into the CNS of rats induced
      for EAE, thereby lessening the histological changes and clinical signs and thus
      ameliorating the disease. These observations indicate that Lovastatin treatment
      may be of therapeutic value against inflammatory disease process associated with
      infiltration of activated mononuclear cells into the tissue.

PMID- 11592112
TI  - Diminished frequency of interleukin-10-secreting, T-cell receptor peptide
      reactive T cells in multiple sclerosis patients might allow expansion of
      activated memory T cells bearing the cognate BV gene.
AB  - T cells responsive to T-cell receptor (TCR) determinants may regulate pathogenic
      Th1 responses in patients with multiple sclerosis (MS) through interleukin (IL)
      10-dependent bystander suppression. In this study, innate IL-10- and interferon
      (IFN)-gamma-secreting T cells responsive to TCR peptides were quantified in
      peripheral blood mononuclear cells of MS patients and healthy controls (HC) using
      the ELISPOT assay. Most HC had vigorous IL-10 but low IFN-gamma frequencies to
      BV5S2 and BV6S1 peptides. In contrast, MS patients had significantly lower IL-10
      frequency responses to the TCR peptides but normal responses to concanavalin A.
      Patients undergoing TCR-peptide vaccination had moderate responses that
      fluctuated in concert with vaccination. In an MS patient and HC, expression of
      BV6S1 by activated memory T cells was inversely associated with the presence of
      IL-10-secreting BV6S1-reactive T cells. These results suggest that MS patients
      have diminished frequencies of innate TCR-reactive T cells that may allow
      oligoclonal expansion of activated autoreactive Th1 effector cells expressing
      cognate V genes.

PMID- 11592111
TI  - Vitamin E suppression of microglial activation is neuroprotective.
AB  - Neurotoxic microglial-neuronal interactions have been implicated in the
      pathogenesis of various neurodegenerative diseases such as Alzheimer's disease,
      and vitamin E has been shown to have direct neuroprotective effects. To determine
      whether vitamin E also has indirect neuroprotective effects through suppression
      of microglial activation, we used a microglial-neuronal coculture.
      Lipopolysaccharide (LPS) treatment of a microglial cell line (N9) induced a time
      dependent activation of both p38 mitogen-activated protein kinase (p38 MAPK) and
      nuclear factor-kappaB (NFkappaB), with consequent increases in interleukin-1alpha
      (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO)
      production. Differentiated neuronal cells (PC12 cells treated with nerve growth
      factor) exhibited marked loss of processes and decreased survival when cocultured
      with LPS-activated microglia. Preincubation of microglia with vitamin E
      diminished this neurotoxic effect, independently of direct effects of the
      antioxidant on the neuronal cells. Microglial NO production and the induction of
      IL-1alpha and TNFalpha expression also were attenuated by vitamin E. Such
      antiinflammatory effects of vitamin E were correlated with suppression of p38
      MAPK and NFkappaB activation and were mimicked by an inhibition of either p38
      MAPK (by SB203580) or NFkappaB (by decoy oligonucleotides). These results suggest
      that, in addition to the beneficial effects of providing direct antioxidant
      protection to neurons reported by others, vitamin E may provide neuroprotection
      in vivo through suppression of signaling events necessary for microglial
      activation.

PMID- 11592113
TI  - Domoic acid-induced neuronal damage in the rat hippocampus: changes in apoptosis
      related genes (bcl-2, bax, caspase-3) and microglial response.
AB  - Domoic acid (DA), a potent neurotoxin, administered intravenously (0.75 mg/kg
      body weight) in adult rats evoked seizures accompanied by nerve cell damage in
      the present study. Neuronal degeneration and microglial reaction in the
      hippocampus were investigated, and the temporal profile of bcl-2, bax, and
      caspase-3 genes in cell death or survival was assessed following the
      administration of DA. Nissl staining showed darkly stained degenerating neurons
      in the hippocampus following the administration of DA at 1-21 days, the
      degeneration being most severe at 5 days. Ultrastructural study in CA1 and CA3
      regions of hippocampus revealed two types of neuronal degeneration, cells that
      exhibited swollen morphology and shrunken electron-dense cells. Immunoreactivity
      of Bcl-2 and Bax was increased considerably at 16 hr and 24 hr in the neurons of
      the hippocampus following DA administration. No significant change was observed
      in the immunoreactivity of caspase-3 in the controls and DA-treated rats at any
      time interval. Microglial cells in the hippocampus showed intense immunoreaction
      with the antibodies OX-42 and OX-6 at 1-21 days after DA administration,
      indicating the up-regulation of complement type 3 receptors and major
      histocompatibility complex type II antigens for increased phagocytic activity and
      antigen presentation, respectively. Terminal deoxynucleotidyl-transferase
      mediated dUTP nick end labeling (TUNEL) showed occasional positive neurons in the
      CA1 and CA3 regions at 5 days after DA administration, with no positive cells in
      the controls. RT-PCR analysis revealed that bcl-2 and bax mRNA transcripts in the
      hippocampus were significantly increased at 16 hr and gradually decreased at 24
      hr following the administration of DA. Although bax and bcl-2 mRNA expression is
      rapidly induced at early stages, in situ hybridization analysis revealed complete
      loss of bcl-2, bax, and caspase-3 mRNA at 24 hr after DA administration in the
      region of neuronal degeneration in the hippocampus. These results indicate that
      the pattern of neuronal degeneration observed during DA-induced excitotoxic
      damage is mostly necrotic.

PMID- 11592114
TI  - Time course studies on the effectiveness of tetrodotoxin in reducing consequences
      of spinal cord contusion.
AB  - Focal injection of the sodium channel blocker tetrodotoxin (TTX) into the injury
      site at either 5 or 15 min after a standardized thoracic contusion spinal cord
      injury (SCI) reduces white matter pathology and loss of axons in the first 24 hr
      after injury. Focal injection of TTX at 15 min after SCI also reduces chronic
      white matter loss and hindlimb functional deficits. We have now tested the
      hypothesis that the reduction in chronic deficits with TTX treatment is
      associated with long-term preservation of axons after SCI and compared both acute
      (24 hr) and chronic (6 weeks) effects of TTX administered at 15 min prior to and
      5 min or 4 hr after SCI. Our results indicate a significant reduction of acute
      white matter pathology in rats treated with TTX at 15 min before and 5 min after
      injury but no effect when treatment was delayed until 4 hr after contusion.
      Compared with injury controls, groups treated with TTX at 5 min and 4 hr after
      injury did not show a significant deficit reduction, nor was there a significant
      sparing of white matter at 6 weeks compared with injury controls. In contrast,
      the group treated with TTX at 15 min before SCI demonstrated significantly
      reduced hindlimb functional deficits beginning at 1 week after injury and
      throughout the 6 weeks of the study. This was associated with a significantly
      higher axon density in the ventromedial white matter at 6 weeks. The results
      demonstrate that blockade of sodium channels preserves axons from loss after SCI
      and points to the importance of time of administration of such drugs for
      therapeutic effectiveness.

PMID- 11592115
TI  - Tau and HMW tau phosphorylation and compartmentalization in apoptotic neuronal
      PC12 cells.
AB  - In the Alzheimer disease brain, the microtubule-associated protein tau is
      hyperphosphorylated. There is also evidence that apoptotic-like processes may
      contribute to the neuronal loss in AD. In an apoptotic model that involves
      replating neuronal PC12 cells without serum and nerve growth factor (NGF), tau
      was hyperphosphorylated. During replating, however, neurites are removed. Here,
      differentiated cells were maintained in serum-free media before growth factor
      removal, thus maintaining neuritic processes during the apoptotic process and
      allowing for evaluation of neuritic changes. Tau phosphorylation, evaluated by
      immunoblotting and immunocytochemistry, was compared with various measures of
      cell death. Compared with control, NGF-deprived cells exhibited gradual and
      consistent increases of lactate dehydrogenase release over a 5-day period and a
      peak of caspase-3 activity at Day 2 after NGF removal. Nuclear staining
      demonstrated chromatin condensation in NGF-deprived cells. Apoptotic cells had
      thickened, tortuous, and shortened neuritic processes compared with control
      cells. Immunoblotting showed an increase in both tau and high molecular weight
      (HMW) tau phosphorylation during the apoptotic process. Immunoreactivity of both
      tau isoforms shifted from the detergent insoluble cytoskeleton to the detergent
      soluble compartment in the apoptotic cells. The microtubule binding of both tau
      isoforms from apoptotic cells also was impaired. Immunoblotting of purified
      plasma membrane showed preferential association of HMW tau with the plasma
      membrane during apoptosis. Also, plasma membrane-associated HMW tau was more
      phosphorylated during apoptosis. Immunocytochemistry demonstrated increased tau
      phosphorylation in most apoptotic cells, especially in the neurites. Tau was,
      however, dephosphorylated cells in the last stages of apoptosis.

PMID- 11592116
TI  - Channel activity of deamidated isoforms of prion protein fragment 106-126 in
      planar lipid bilayers.
AB  - Using the lipid bilayer technique, we have found that age-related derivatives,
      PrP[106-126] (L-Asp108) and PrP[106-126] (L-iso-Asp108), of the prion protein
      fragment 106-126 (PrP[106-126] (Asn108)) form heterogeneous ion channels. The
      deamidated isoforms, PrP[106-126] (L-Asp108) and PrP[106-126] (L-iso-Asp108),
      showed no enhanced propensity to form heterogeneous channels compared with
      PrP[106-126] (Asn108). One of the PrP[106-126] (L-Asp108)- and PrP[106-126] (L
      iso-Asp108)-formed channels had three kinetic modes. The current-voltage (I-V)
      relationship of this channel, which had a reversal potential, E(rev), between -40
      and -10 mV close to the equilibrium potential for K+ (E(K)-35 mV), exhibited a
      sigmoidal shape. The value of the maximal slope conductance (g(max)) was 62.5 pS
      at positive potentials between 0 and 140 mV. The probability (P(o)) and the
      frequency (F(o)) of the channel being open had inverted and bell-shaped curves,
      respectively, with a peak at membrane potential (V(m)) between -80 and +80 mV.
      The mean open and closed times (T(o) and T(c)) had inverted bell-shaped curves.
      The biophysical properties of PrP[106-126] (L-Asp108)- and PrP[106-126] (L-iso
      Asp108)-formed channels and their response to Cu(2+) were similar to those of
      channels formed with PrP[106-126] (Asn108). Cu(2+) shifted the kinetics of the
      channel from being in the open state to a "burst state" in which rapid channel
      activities were separated by long durations of inactivity. The action of Cu(2+)
      on the open channel activity was both time-dependent and voltage-dependent. The
      fact that Cu(2+) induced changes in the kinetics of this channel with no changes
      in the conductance of the channel indicated that Cu(2+) binds at the mouth of the
      channel. Consistently with the hydrophilic and structural properties of PrP[106
      126], the Cu(2+)-induced changes in the kinetic parameters of this channel
      suggest that the Cu(2+) binding site could be located at M(109) and H(111) of
      this prion fragment.

PMID- 11592117
TI  - Estrogen stimulates brain-derived neurotrophic factor expression in embryonic
      mouse midbrain neurons through a membrane-mediated and calcium-dependent
      mechanism.
AB  - We have provided evidence that 17beta-estradiol (E) synthesized in the midbrain
      promotes the differentiation of midbrain dopamine neurons through nonclassical
      steroid action. Because these developmental effects resemble those reported for
      brain-derived neurotrophic factor (BDNF), we hypothesized that E influences
      dopaminergic cell differentiation through a BDNF-dependent mechanism. Competitive
      RT-PCR and ELISA techniques were employed to study first the developmental
      pattern of BDNF and trkB expression in the mouse midbrain. BDNF protein/mRNA
      levels peaked postnatally, whereas trkB did not fluctuate perinatally. To prove
      the hypothesis that E regulates BDNF expression in vivo, fetuses and newborns
      were treated with the aromatase antagonist CGS 16949A. CGS 16949A exposure
      reduced midbrain BDNF mRNA/protein levels. The coapplication of CGS 16949A and E
      abolished this effect. Midbrain cultures from mouse fetuses were used to
      investigate intracellular signaling mechanisms involved in transmitting E
      effects. Estrogen increased expression of BDNF but not of other neurotrophins. As
      concerns the related signaling mechanism, these effects were antagonized by
      interrupting intracellular Ca(2+) signaling with BAPTA and thapsigargin but not
      by the estrogen receptor antagonist ICI 182,780. Insofar as E effects on BDNF
      mRNA expression were inhibited by cycloheximide, it appears likely that other,
      not yet characterized intermediate proteins take part in the estrogenic
      regulation of BDNF expression. We conclude that E exerts its stimulatory effect
      on the differentiation of dopaminergic neurons by coordinating BDNF expression.
      This particular E effect appears to be transmitted through Ca(2+)-dependent
      signaling cascades upon activation of putative membrane estrogen receptors.

PMID- 11592118
TI  - Distribution of intraventricularly administered antiamyloid-beta peptide (Abeta)
      antibody in the mouse brain.
AB  - There is considerable interest in utilizing the intracerebroventricular (icv)
      route of administration of antibodies in the brain for various studies and for
      the therapy of malignancies, but very little is known about the anatomic extent
      of distribution of the antibody in brain after injection into the third
      ventricle. To explore the potential for icv administration of antiamyloid-beta
      peptide (Abeta) in reducing Abeta toxicity in brain in Alzheimer's disease, we
      first mapped the time course and path of transit of horseradish peroxidase (HRP)
      labeled antibody. The results show that, after a single injection into the mouse
      third venticle, the HRP-labeled antibody is localized within the
      microvasculature, first that of the corticohippocampal region close to the site
      of injection at 3 hr. By 24 hr, the antibody is distributed throughout the
      hippocampus and frontoparietal cortex close to the injection site, as well as in
      the deep and outer cerebral cortex and cerebellar cortex remote from the
      injection site. The injected antibody is almost entirely removed by 4 days.
      Therefore, the antibody had diffused throughout all the brain by 24 hr, showing
      the feasibility of small quantities of anti-Abeta antibody infused into the third
      ventricle to reach extracellular epitopes throughout the brain parenchyma
      rapidly.

PMID- 11592119
TI  - Activation of the peroxisome proliferator-activated receptor-alpha enhances cell
      death in cultured cerebellar granule cells.
AB  - Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a member of the
      steroid hormone receptor superfamily. In rodents, PPARalpha alters genes involved
      in cell cycle regulation in hepatocytes. Some of these genes are implicated in
      neuronal cell death. Therefore, in this study, we examined the toxicological
      consequence of PPARalpha activation in rat primary cultures of cerebellar granule
      neurons. Our studies demonstrated the presence of PPARalpha mRNA in cultures by
      reverse transcriptase-polymerase chain reaction. After 10 days in vitro,
      cerebellar granule neuron cultures were incubated with the selective PPARalpha
      activator 4-chloro-6-(2,3-xylidino)2-pyrimidinylthioacetic acid (Wy-14,643). The
      inherent toxicity of Wy-14,643 and the effect of PPARalpha activation following
      toxic stimuli were assessed. In these studies, neurotoxicity was induced through
      reduction of extracellular [KCl] from 25 mM to 5.36 mM. We observed no inherent
      toxicity of Wy-14,643 (24 hr) in cultured cerebellar granule cells. However,
      after reduction of [KCl], cerebellar granule cell cultures incubated with Wy
      14,643 showed significantly greater toxicity than controls. These results suggest
      a possible role for PPARalpha in augmentation of cerebellar granule neuronal
      death after toxic stimuli.

PMID- 11592120
TI  - Effect of liposomes containing cerebroside and cerebroside sulfate on
      cytoskeleton of cultured oligodendrocytes.
AB  - Oligodendrocytes (OLs) and the myelin produced by them are enriched in two
      glycosphingolipids, galactosylceramide (GalC) and its sulfated form, cerebroside
      sulfate (CBS). We showed earlier that these two glycolipids in opposed liposomal
      membranes or in methanol solution can adhere to each other. Here we have examined
      the potential effect of an interaction between GalC/CBS in apposed membranes of
      oligodendrocytes (OLs) by incubating cultured OLs with GalC/CBS-containing
      liposomes and observing the effect on the membrane sheets produced by OLs and on
      the distribution of OL constituents using fluorescent antibodies and confocal
      microscopy. The GalC/CBS-containing liposomes caused redistribution or a decrease
      in the density of anti-GalC and anti-MBP staining but had no effect on the
      density or distribution of staining by anti-PI(4,5)P(2) that remained uniformly
      distributed in the membrane sheets. There was no apparent change in the area of
      the membrane sheets nor in the amount of MBP in OL membranes, as determined by
      slot blots. In addition, the GalC/CBS-containing liposomes caused
      depolymerization of microtubules and actin filaments suggesting that the
      interaction of GSL-containing liposomes with the extracellular surface of the OL
      caused transmission of a signal across the membrane. Because these two
      glycolipids can adhere to each other across apposed membranes, the liposomal
      glycolipids may be interacting with a GalC/CBS-enriched signaling domain in the
      OL plasma membrane.

PMID- 11592121
TI  - Selective effect of hypothyroidism on expression of myelin markers during
      development.
AB  - Thyroid hormones are critical for maturation of the central nervous system. In a
      previous study, we showed a change in the pattern of mature myelinated nerve
      fibers by 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) in developing
      hypothyroid animals, which suggests a possible role for thyroid hormones in
      myelin compaction. The classical myelin markers myelin basic protein (MBP) and
      proteolipidic protein (PLP) are expressed later in oligodendroglial development,
      when myelin sheath formation is in progress. A myelin constituent designated
      myelin-associated/oligodendrocytic basic protein (MOBP) has been identified and
      related to myelin compaction. We assessed the developmental sequence of
      appearance of CNPase, MBP, MOPB, and PLP proteins in cerebellum (Cb) and corpus
      callosum (cc) in an experimental hypothyroidism model. The appearance of both
      MOBP isoforms occurred at postnatal day (P)25 and P30 in cc and Cb, respectively,
      followed by an increase with age in the control group. However, all the MOBP
      isoforms were weakly detectable in both regions at P30 from the hypothyroid (H)
      group, and the higher molecular weight isoform remains decreased in cc, even at
      P90. The developmental pattern of expression of CNPase, MBP, and PLP proteins was
      also delayed in the H group. CNPase and MBP expression was recovered in cc and
      Cb, whereas PLP remained below control levels at P90 in cc. Our data show that
      the experimental hypothyroidism affects the developmental pattern of the
      oligodendrocytic/myelin markers. Furthermore, thyroid hormone may modulate
      specific genes, as demonstrated by permanent down-regulation of MOBP and PLP
      expression in adulthood.

PMID- 11592122
TI  - Altered circadian cortisol secretion in Alzheimer's disease: clinical and
      neuroradiological aspects.
AB  - We determined circadian salivary cortisol levels in 18 outpatients affected by
      probable Alzheimer's disease (AD) and looked for a possible correlation with both
      cognitive impairment and brain CT scan findings. The diagnosis of probable AD was
      made according to the NINCDS-ADRDA criteria. The severity of cognitive impairment
      was quantified using the Mini Mental State Examination (MMSE) and the Global
      Deterioration Scale (GDS). Cortisol levels were measured on saliva samples
      collected at 08:00 AM and 08:00 PM. For each sample, a duplicate cortisol
      measurement was performed on 50 microl of saliva by means of a modified
      commercial radioimmunoassay kit. At the same time, 11 of the 18 AD patients
      enrolled also underwent a brain CT scan to estimate cerebral atrophy by using
      linear indexes. The mean value of cortisol levels was significantly higher in AD
      patients than in controls at both the morning and the evening measurements, and
      the circadian fluctuation of cortisol was less marked in AD patients than in
      controls, although this difference did not reach statistical significance.
      Morning cortisol levels were significantly correlated to both the MMSE and the
      GDS scores. A significant correlation was also found between morning cortisol
      levels and all the cerebral atrophy indexes. By contrast, no correlation was
      observed between evening cortisol levels or cortisol circadian fluctuations and
      either cognitive impairment or cerebral atrophy. In conclusion, despite the
      potential biases deriving from the small sample and the limitations of the CT
      scan study, our results suggest that, in AD patients, hypercortisolemia is
      correlated with severity of the disease.

PMID- 11592123
TI  - Enhancement of learning capacity and cholinergic synaptic function by carnitine
      in aging rats.
AB  - The effects of a carnitine derivative, acetyl-L-carnitine (ALCAR), on the
      cognitive and cholinergic activities of aging rats were examined. Rats were given
      ALCAR (100 mg/kg) per os for 3 months and were subjected to the Hebb-Williams
      tasks and a new maze task, AKON-1, to assess their learning capacity. The
      learning capacity of the ALCAR-treated group was superior to that of the control.
      Cholinergic activities were determined with synaptosomes isolated from the
      cortices. The high-affinity choline uptake by synaptosomes, acetylcholine
      synthesis in synaptosomes, and acetylcholine release from synaptosomes on
      membrane depolarization were all enhanced in the ALCAR group. This study
      indicates that chronic administration of ALCAR increases cholinergic synaptic
      transmission and consequently enhances learning capacity as a cognitive function
      in aging rats.

PMID- 11592124
TI  - Brain amino acid metabolism and ketosis.
AB  - The relationship between ketosis and brain amino acid metabolism was studied in
      mice that consumed a ketogenic diet (>90% of calories as lipid). After 3 days on
      the diet the blood concentration of 3-OH-butyrate was approximately 5 mmol/l
      (control = 0.06-0.1 mmol/l). In forebrain and cerebellum the concentration of 3
      OH-butyrate was approximately 10-fold higher than control. Brain [citrate] and
      [lactate] were greater in the ketotic animals. The concentration of whole brain
      free coenzyme A was lower in ketotic mice. Brain [aspartate] was reduced in
      forebrain and cerebellum, but [glutamate] and [glutamine] were unchanged. When
      [(15)N]leucine was administered to follow N metabolism, this labeled amino acid
      accumulated to a greater extent in the blood and brain of ketotic mice. Total
      brain aspartate ((14)N + (15)N) was reduced in the ketotic group. The
      [(15)N]aspartate/[(15)N]glutamate ratio was lower in ketotic animals, consistent
      with a shift in the equilibrium of the aspartate aminotransferase reaction away
      from aspartate. Label in [(15)N]GABA and total [(15)N]GABA was increased in
      ketotic animals. When the ketotic animals were injected with glucose, there was a
      partial blunting of ketoacidemia within 40 min as well as an increase of brain
      [aspartate], which was similar to control. When [U-(13)C(6)]glucose was injected,
      the (13)C label appeared rapidly in brain lactate and in amino acids. Label in
      brain [U-(13)C(3)]lactate was greater in the ketotic group. The ratio of brain
      (13)C-amino acid/(13)C-lactate, which reflects the fraction of amino acid carbon
      that is derived from glucose, was much lower in ketosis, indicating that another
      carbon source, i.e., ketone bodies, were precursor to aspartate, glutamate,
      glutamine and GABA.

PMID- 11592125
TI  - Ammonia-induced production of free radicals in primary cultures of rat
      astrocytes.
AB  - Elevated levels of ammonia in blood and brain result in derangement of cerebral
      function. Recently, lipid peroxidation and oxidative stress have been implicated
      in ammonia neurotoxicity. Because ammonia is primarily detoxified in astrocytes,
      we postulated that pathophysiological concentrations of ammonia might induce free
      radical formation in these cells. To test this hypothesis, we examined the extent
      of free radical production in primary cultures of astrocytes that had been
      preloaded with the fluorescent dye 5- (and 6-)carboxy-2',7'
      dichlorodihydrofluorescein diacetate (DCFDA). DCFDA fluorescence was found to be
      increased in a dose-dependent manner when astrocytes were exposed to 1, 5, and 10
      mM NH(4)Cl. This phenomenon was transitory; it peaked at 2.5 min after exposure
      and declined subsequently. By 2 hr after treatment, DCFDA fluorescence was below
      control level. Addition of catalase or superoxide dismutase to 5 mM NH(4)Cl
      treated astrocytes reduced free radical formation. Pretreatment with 3 mM
      methionine sulfoximine, an inhibitor of glutamine synthetase, also suppressed
      free radical formation by 5 mM NH(4)Cl. The results of this study suggest that
      elevated concentrations of ammonia induce the formation of free radicals in
      astrocytes and that this process is associated with the synthesis of glutamine.
      We propose that astrocyte-derived free radicals may be responsible for some of
      the pathophysiological changes associated with hyperammonemic conditions.

PMID- 11592126
TI  - Blood-brain barrier preservation in the in vitro isolated guinea pig brain
      preparation.
AB  - The morphofunctional preservation of the blood-brain barrier (BBB) was evaluated
      in the isolated guinea pig brain maintained in vitro by arterial perfusion.
      Electron microscopy evaluation after 5 hr in vitro demonstrated that cerebral
      capillaries and BBB specializations in this preparation retain features
      compatible with structural integrity. BBB-impermeable and -permeable atropine
      derivatives arterially perfused to antagonize carbachol-induced fast oscillatory
      activity confirmed the functional preservation of the BBB in vitro. To study BBB
      function further, changes in extracellular K+ concentration during arterial
      perfusion of a high-K+ solution were measured with K+-sensitive electrodes
      positioned in the cortex and, as control, at the brain venous outlet, where the
      solution perfused through the brain arterial system was collected. After 5 hr in
      vitro, the [K+](o) values measured during high-K+ perfusion in the piriform and
      entorhinal cortices were 5.02 +/- 0.17 mM (mean +/- SE) and 5.2 +/- 0.21 mM,
      respectively (n = 6). Coperfusion of the high-K+ solution with the Na+/K+ pump
      blocker ouabain (10 microM; n = 4) induced consistently spreading depression
      preceded by a rise in [K+](o). Finally, sporadic, isolated spots of extravasation
      of the fluorescent marker fluorescein isothiocyanate (FITC)-dextran
      preferentially circumscribed to deep cortical layers was observed in brains
      perfused with FITC-dextran after 5 hr in vitro. The study demonstrates that the
      in vitro isolated guinea pig brain is viable for studying cerebrovascular
      interactions and BBB permeability of compounds active in the central nervous
      system.

PMID- 11592127
TI  - Cannabinoid receptor agonist WIN 55,212-2 inhibits rat cortical dialysate gamma
      aminobutyric acid levels.
AB  - The effects of the cannabinoid receptor agonist WIN 55,212-2 (0.1-5 mg/kg i.p.)
      on endogenous extracellular gamma-aminobutyric acid (GABA) levels in the cerebral
      cortex of the awake rat was investigated by using microdialysis. WIN 55,212-2 (1
      and 5 mg/kg i.p.) was associated with a concentration-dependent decrease in
      dialysate GABA levels (-16% +/- 4% and -26% +/- 4% of basal values,
      respectively). The WIN 55,212-2 (5 mg/kg i.p.) induced-inhibition was
      counteracted by a dose (0.1 mg/kg i.p.) of the CB(1) receptor antagonist
      SR141716A, which by itself was without effect on cortical GABA levels. These
      findings suggest that cannabinoids decrease cortical GABA levels in vivo, an
      action that might underlie some of the cognitive and behavioral effects of acute
      exposure to marijuana.

PMID- 11592130
TI  - Graphical Abstract.

PMID- 11592128
TI  - Dorsal root ganglia neurite extension is inhibited by mechanical and chondroitin
      sulfate-rich interfaces.
AB  - Glial scar formation plays a critical role in the regenerative failure in the
      central nervous system of adult mammals through the formation of mechanical or
      biochemical barriers as a result of its molecular composition. In this study, we
      report an in vitro model to study growth-cone behavior at controlled 3D
      interfaces using layered agarose hydrogels. The behavior of growth cones from
      embryonic day 9 (E9) chick dorsal root ganglia (DRGs) at interfaces that were
      mismatched in terms of their elasticity or chondroitin sulfate content was
      quantitatively determined. A mechanical barrier formed by the elasticity mismatch
      of layered agarose gels greatly influenced the ability of neurites from E9 DRGs
      to cross the 3D interface. To form chondroitin sulfate-rich interfaces,
      chondroitin sulfate B was covalently coupled to agarose hydrogel. Compared with
      unmodified agarose gels, the presence of CS-B-modified agarose gels at the
      interface significantly inhibited E9 DRGs neurites. After treatment of CS-B
      modified agarose gels with chondroitinase ABC, the inhibitory effects of CS-B at
      the interface were significantly decreased. The effect of doping CS-B gels with
      laminin 1 (LN-1)-coupled agarose gels was investigated as a potential strategy to
      overcome inhibitory interfaces. When CS-B agarose gels were doped with LN-1
      coupled agarose gels, DRG neurite's ability to cross 3D interfaces was
      significantly enhanced compared with that of non-LN-1-containing interfaces
      presenting equivalent CS-B. Our in vitro model may be used to study the influence
      of individual components of glial scar on inhibition as well as to design
      strategies to overcome this inhibition.

PMID- 11592131
TI  - Catalyzed Asymmetric Arylation Reactions.
AB  - Addition and substitution reactions with carbon nucleophiles are fundamental
      processes in organic synthesis, and the development of general catalytic
      asymmetric variants thereof is still a major challenge today. In contrast to
      enantioselective alkyl transfer reactions, the corresponding arylations have not
      yet reached a high level of maturity. The existing protocols are either of no
      general applicability or are limited in terms of selectivity. This article
      summarizes established routes for catalytic asymmetric aryl transfer together
      with the latest developments in this area. The scope and limitations of this
      reaction are discussed.

PMID- 11592132
TI  - Investigating and Engineering Enzymes by Genetic Selection.
AB  - Natural enzymes have arisen over millions of years by the gradual process of
      Darwinian evolution. The fundamental steps of evolution-mutation, selection, and
      amplification-can also be exploited in the laboratory to create and characterize
      protein catalysts on a human timescale. In vivo genetic selection strategies
      enable the exhaustive analysis of protein libraries with 10(10) different
      members, and even larger ensembles can be studied with in vitro methods.
      Evolutionary approaches can consequently yield statistically meaningful insight
      into the complex and often subtle interactions that influence protein folding,
      structure, and catalytic mechanism. Such methods are also being used increasingly
      as an adjunct to design, thus providing access to novel proteins with tailored
      catalytic activities and selectivities.

PMID- 11592133
TI  - Not a Library I am grateful to Albert Eschenmoser, Sylvie Coyaud, and Henning
      Hopf for their comments. 

PMID- 11592134
TI  - Medicinal Chemistry: Challenges and Opportunities.

PMID- 11592135
TI  - Catalytic C-H Activation of sp(3) C-H Bonds in alpha-Position to a Nitrogen Atom
      Two New Approaches I thank Professor E. Winterfeldt for his generous support of
      my research. 

PMID- 11592136
TI  - Going Beyond sigma Complexation: Nonclassical Interligand Interactions of Silyl
      Groups with Two and More Hydrides Financial support from the Russian Fund for
      Basic Research is gratefully acknowledged. 

PMID- 11592137
TI  - Synthesis and Structural Characterization of the First Uranium Cluster Containing
      an Isopolyoxometalate Core The authors gratefully acknowledge support provided by
      the Division of Chemical Sciences, Office of Basic Energy Sciences (LANL and
      LBNL), and the LANL Laboratory Directed Research and Development Program. 

PMID- 11592138
TI  - Rational Molecular Design and EPC Synthesis of a Type VI beta-Turn Inducing
      Peptide Mimetic This work was supported by the BMBF and the Fonds der Chemischen
      Industrie. EPC=enantiomerically pure compound. 

PMID- 11592140
TI  - Zero-Strain Intercalation Cathode for Rechargeable Li-Ion Cell.

PMID- 11592139
TI  - Atomic Force Microscope Studies on Condensation of Plasmid DNA with
      Functionalized Fullerenes This research was supported by Grant-in-Aid for
      Specially Promoted Research from Ministry of Education, Culture, Sports, Science,
      and Technology. 

PMID- 11592141
TI  - Aromatic Mercury Clusters in Ancient Amalgams Work done at Utah State University
      is supported by the donors to The Petroleum Research Fund, administered by the
      American Chemical Society. Work done at Iowa State University is supported by
      Basic Energy Sciences, the U.S. Department of Energy. Work done at Washington
      State University is supported by the National Science Foundation (DMR-0095828)
      and performed at the W. R. Wiley Environmental Molecular Sciences Laboratory, a
      national scientific user facility sponsored by DOE's Office of Biological and
      Environmental Research and located at Pacific Northwest National Laboratory,
      which is operated for DOE by Battelle. 

PMID- 11592142
TI  - Allosteric Fluoride Anion Recognition by a Doubly Strapped Porphyrin This work
      was funded by the Department of Energy, by a contract through Bechtel Nevada, and
      the Office of Naval Research. M.T. thanks the Ministry of Education, Science and
      Culture of Japan for financial support and Prof. Itaru Hamachi and Mr. Masato
      Ikeda at Kyushu University for helpful discussions. 

PMID- 11592143
TI  - Radical Shuttling in a Protein: Ribose Pseudorotation Controls Alkyl-Radical
      Transfer in the Coenzyme B(12) Dependent Enzyme Glutamate Mutase This work was
      supported by the Osterreichische Akademie der Wissenschaften (APART fellowship
      614), the Osterreichische Fonds zur Forderung der wissenschaftlichen Forschung
      (FWF-project 11599), and the European Commission (TMR project number ERB 4061 PL
      95-0307). Crystallographic data were collected at the EMBL-beamline BW7B at DESY
      in Hamburg, Germany. We thank the beamline scientists for their assistance, and
      Ingrid Dreveny, Gunter Gartler, Gerwald Jogl, and Oliver Sauer for their help
      during data collection. This research emerged from a collaboration with Prof. W.
      Buckel (Marburg) who supplied us with clones of the glutamate mutase proteins. 

PMID- 11592144
TI  - "Carving on the Nanoscale": Polymers for the Site-Specific Dissolution of Calcium
      Phosphate Financial support by the Max Planck Society is gratefully acknowledged
      We thank Dr. H. Colfen, MPI Golm and Dr. H. Schnablegger, Universitat Hamburg,
      for helpful discussions. 

PMID- 11592145
TI  - A Large, Novel Polyoxotungstate: [As$?rm{^{III}_{6}}$W(65)O(217)(H(2)O)(7)](26-)
      U.K. thanks the American University of Beirut for research support via a URB
      grant. We thank Nebebech Belai for recording the NMR spectrum. Figures 1-4 were
      generated by Diamond Version 2.1b (copyright Crystal Impact GbR). 

PMID- 11592146
TI  - Catalytic C-C Bond Formation through Selective Activation of C-F Bonds N
      Heterocyclic Carbenes, Part 30. This work was supported by the Deutsche
      Forschungsgemeinschaft (DFG), the Bayerischer Forschungsverbund Katalyse
      (FORKAT), and the Fonds der Chemischen Industrie (studentships for V.P.W.B. and
      T.W.). We thank K. Ofele, TU Munchen, and F. L. Taw, UNC Chapel Hill, for helpful
      discussions. Part 29: W. A. Herrmann, V. P. W. Bohm, C. W. K. Gstottmayr, M.
      Grosche, C.-P. Reisinger, T. Weskamp, J. Organomet. Chem. 2001, 617/618, 616-628.

PMID- 11592147
TI  - Oxidative Opening of Cycloalkanols: An Efficient Entry to omega-Iodocarbonyl
      Compounds This research was supported by DGES (Grant PB97-1271). F.G.-B. thanks
      FICYT for a fellowship. 

PMID- 11592148
TI  - Chromium-Copper Exchange of Fischer Carbene Complexes: X-Ray Crystal Structure of
      a [Cu{=CR(1)(OR(2))}(MeCN)(Et(2)O)][PF(6)] Complex This work was supported by
      DGICYT (PB97-1271) and CICYT (BQU2000-0219). O.L. thanks the Fonds der Chemischen
      Industrie for a postdoctoral fellowship. 

PMID- 11592149
TI  - Fmoc-Compatible Solid-Phase Peptide Synthesis of Long C-Terminal Peptide
      Thioesters The authors are grateful to the ETH-Zurich and Novartis Pharma AG for
      support of this work. Fmoc=9-fluorenylmethoxycarbonyl. 

PMID- 11592150
TI  - Pt(II) Binding to N1 of Cytosine: Strengthening the Watson-Crick Pair with
      Guanine and yet Confining Its pH Existence Range This work was supported by the
      Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. 

PMID- 11592151
TI  - Electrochemical Regeneration of Low-Valent Indium(I) Species as Catalysts for C-C
      Bond Formations This work was supported by the Deutsche Forschungsgemeinschaft.
      We thank Prof. W. Schnick, W. Wunschheim, and S. Rannabauer for the measurement
      of the Raman spectra. 

PMID- 11592152
TI  - Synthesis and Properties of the First [4.4]Ferrocenophane-1,3,15,17-tetrayne This
      work was supported by the Fonds der Chemischen Industrie, the Dr. Otto Rohm
      Gedachtnisstiftung, and the Degussa AG. We thank Frau Sabine Foro for her
      assistance in the crystal-structure analysis, and Dr. Jan Friedrich (MPI fur
      Polymerforschung, Mainz) and Dipl.-Chem. Jorg Classen (Universitat Heidelberg)
      for undertaking the cyclic voltammetric measurements. 

PMID- 11592153
TI  - New Building Blocks in Amide Chemistry-N-Lithiobis(trimethylstannyl)amine and N
      Lithiotrimethylstannyl(trimethylsilyl)amine This work was supported by the
      Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. 

PMID- 11592154
TI  - Highly Selective Catalyst Systems for the Hydroformylation of Internal Olefins to
      Linear Aldehydes This work was supported by Oxeno Olefinchemie GmbH and the State
      of Mecklenburg-West Pommerania. Dr. C. Fischer and Mrs. S. Buchholz are thanked
      for their excellent technical support. 

PMID- 11592155
TI  - Nucleophilic Trapping of pi-Allylpalladium Intermediates Generated by
      Carbopalladation of Bicyclopropylidene: A Novel Three-Component Reaction
      Cyclopropyl Building Blocks in Organic Synthesis, Part 73. This work was
      supported by the Fonds der Chemischen Industrie and Bayer AG. We are indebted to
      Dr. B. Knieriem, Gottingen, for his careful proofreading of the final manuscript.
      Part 72: A. de Meijere, M. von Seebach, S. I. Kozhushkov, S. Cicchi, T. Dimoulas,
      A. Brandi, Eur. J. Org. Chem. 2001, in press; Part 71: A. de Meijere, S. I.
      Kozhushkov, D. Faber, V. Bagutskii, R. Boese, T. Haumann, R. Walsh, Eur. J. Org.
      Chem. 2001, in press. 

PMID- 11592156
TI  - Insertion Reactions of Nitriles into the P-C Bond of [(eta(1)
      C(5)Me(5))P{W(CO)(5)}(2)]-A Novel Approach to Phosphorus-Containing Heterocycles
      This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der
      Chemischen Industrie. M. Schiffer thanks the Fonds der Chemischen Industrie for a
      PhD fellowship. 

PMID- 11592157
TI  - Asymmetric Catalysis in Diversity-Oriented Organic Synthesis: Enantioselective
      Synthesis of 4320 Encoded and Spatially Segregated Dihydropyrancarboxamides We
      thank the National Institute of General Medical Sciences (GM-52067) for support
      of this research, and Dr. John Tallarico and Max Narovlyansky at the ICCB for
      generously providing resin for the library synthesis. We thank Dr. Helen
      Blackwell and Lucy Perez for expert help with library encoding. We are grateful
      to Prof. Eric Jacobsen and Prof. Scott Denmark for the use of their chiral
      stationary phase high pressure liquid chromatograph and supercritical fluid
      chromatograph, respectively. The Harvard ICCB is supported by Merck & Co., Merck
      KGaA, the Keck Foundation, and the National Cancer Institute. R.A.S. is a
      Research Associate and S.L.S. is an Investigator with the Howard Hughes Medical
      Institute at the Department of Chemistry and Chemical Biology, Harvard
      University. 

PMID- 11592158
TI  - Decoding Products of Diversity Pathways from Stock Solutions Derived from Single
      Polymeric Macrobeads H.E.B. and L.P. contributed equally to this work. We thank
      the National Institute of General Medical Sciences (GM-52067) for the support of
      this research. We are especially grateful to Dr. Andrew Tyler for expert mass
      spectroscopy support. The Harvard ICCB is supported by Merck & Co., Merck KGaA,
      the Keck Foundation, and the National Cancer Institute. H.E.B. is supported by a
      postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical
      Research (sponsored by Merck & Co.). L.P. is a Research Fellow, and S.L.S. is an
      Investigator with the Howard Hughes Medical Institute at the Department of
      Chemistry and Chemical Biology, Harvard University. 

PMID- 11592159
TI  - Highly Enantioselective Hydrogenation of Acyclic Imines Catalyzed by Ir-f
      Binaphane Complexes This work was supported by a NIH grant and a Dreyfus Teaching
      Scholar Award. We acknowledge a generous loan of precious metals from Johnson
      Mathey Inc. and a gift of chiral GC columns from Supelco. 

PMID- 11592160
TI  - Porous Polymer Films and Honeycomb Structures Made by the Self-Organization of
      Well-Defined Macromolecular Structures Created by Living Radical Polymerization
      Techniques We acknowledge a DAAD (German Academic Exchange Service) Scholarship
      (HSPIII) for Dr. M. H. Stenzel-Rosenbaum. 

PMID- 11592161
TI  - Rapid Access to Diverse Arrays of Chiral 3,4-Diazaphospholanes We thank the
      Department of Energy, Office of Basic Energy Sciences for financial support of
      this work. All crystal-structure determinations were performed by Dr. Doug Powell
      or Dr. Ilyea Guzei. The cone-angle measurements were made with the gracious
      assistance of Dr. David White of the UNC-Wilmington. 

PMID- 11592162
TI  - Acentric Extended Solids by Self Assembly of 4,4'-Bipyrazolyls The authors
      gratefully acknowledge support from the Deutsche Forschungsgemeinschaft and the
      Sachsisches Staatsministerium fur Wissenschaft und Kunst. 

PMID- 11592163
TI  - Multicarbocycle Formation Mediated by Arenoporphyrin 1,4-Diradicals: Synthesis of
      Picenoporphyrins This work was supported by grant CHE-99-04076 from the U.S.
      National Science Foundation and grant HL-22252 from the U.S. National Institutes
      of Health. The Bruker SMART 1000 diffractometer was funded in part by NSF
      Instrumentation grant CHE-98-08259. 

PMID- 11592164
TI  - Olefin Metathesis with 1,1-Difluoroethylene This work was funded by the U.S.
      National Science Foundation. T.M.T. also acknowledges the U.S. Department of
      Defense for a NDSEG graduate fellowship. We thank L. M. Henling (Caltech) for
      contributions to the crystallography and M. S. Sanford (Caltech) for assistance
      with magnetization-transfer experiments. 

PMID- 11592165
TI  - A Unique Asymmetric [Mn$?rm{^{II}_{3}}$] Triple-Stranded Helicate from a
      Symmetric Pentadentate Ligand Financial support by the European Union, under
      contract HPMF-CT-1999-00113 (Marie Curie Fellowship to G.A.), the WFMO (J.R.),
      and the CW-NOW (A.L.S.) is thankfully acknowledged. 

PMID- 11592166
TI  - A Free-Energy Relationship between the Rate of Acidic Hydrolysis of Glycosides
      and the pK(a) of Isofagomines We thank Ib Thomsen, Xifu Liang, Steen U. Hansen
      and Huizhen Liu for providing us with compound samples, and the Lundbeck
      Foundation and Danish Natural Science Research Council (THOR programme) for
      financial support. 

PMID- 11592167
TI  - A Disilane Containing Two Heptacoordinate Silicon Atoms and Dithiocarboxylate
      Ligands This work was partially supported by a Grant-in-Aid for Scientific
      Research on Priority Area "Creation of Delocalized Electronic Systems" from the
      Ministry of Education, Science, Sports and Culture, Japan (No. 12020215). We also
      thank Shin-etsu Chemical Co., Ltd. and Tosoh Finechem Corporation for gifts of
      organosilicon and alkyllithium compounds, respectively. 

PMID- 11592168
TI  - Generation and Stabilization of D(6h) and C(2v) Valence Tautomeric Structures of
      the Rhodizonate Dianion in Hydrogen-Bonded Host Lattices This work was supported
      by the Hong Kong Research Grants Council Earmarked Grant (CUHK 4206/99P). 

PMID- 11592169
TI  - A Practical and Highly Efficient Aminohydroxylation of Unsaturated Carboxylic
      Acids We thank the National Institute of General Medical Sciences, the National
      Institutes of Health (GM 28384), National Science Foundation (CHE-9985553), and
      the W. M. Keck Foundation for financial support. We are also grateful to Prof. M.
      G. Finn, Dr. Wallace Pringle, and Dr. A. Erik Rubin for many helpful discussions.

PMID- 11592170
TI  - Palladium-Catalyzed Synthesis of Aryl Ketones from Boronic Acids and Carboxylic
      Acids or Anhydrides We thank M. Rossig and L. Winkel for technical assistance,
      Prof. Dr. M. T. Reetz for generous support and constant encouragement, and the
      DFG for financial support. 

PMID- 11592171
TI  - A Polyhedral Aluminum Compound with an Al(4)C(4)N(4) Framework This work was
      supported by the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen
      Industrie, and the Gottinger Akademie der Wissenschaften. 

PMID- 11592172
TI  - Anion-Templated Syntheses of Rhombohedral Silver-Alkynyl Cage Compounds.

PMID- 11592173
TI  - The Self-Assembly of an Unexpected, Unique Supramolecular Triangle Composed of
      Rigid Subunits This research was supported by the National Science Foundation
      (CHE-9818472) and the Austrian Foundation for Scientific Research (FWF) through
      an Erwin Schrodinger Fellowship for M. Schweiger. 

PMID- 11592174
TI  - Microencapsulated Palladium Catalysts: Allylic Substitution and Suzuki Coupling
      Using a Recoverable and Reusable Polymer-Supported Palladium Catalyst This work
      was partially supported by a Grant-in-Aid for Scientific Research from the
      Ministry of Education, Science, Sports, and Culture, Japan. R.A. thanks the JSPS
      fellowship for Japanese Junior Scientists. 

PMID- 11592175
TI  - A Light-Harvesting tert-Phosphane Ligand Bearing a Ruthenium(II) Polypyridyl
      Complex as Substituent.

PMID- 11592176
TI  - The Hexaphosphapentaprismane P(6)C(4)tBu(4): A "Jaws-Like" Cage Molecule That
      Bites! We thank the EPSRC (M.D.F., J.F.N.), the AEC of Syria, Damascus
      (M.M.A.K.), The Royal Society (J.F.N., L.N.), and FKFP-0029/2000 (L.N.) for
      financial support. 

PMID- 11592177
TI  - One Site Fits All: SpectroscopyNOW.

PMID- 11592179
TI  - Graphical Abstract.

PMID- 11592180
TI  - An Allosteric Ribozyme Regulated by Doxycyline This work was supported by Aventis
      Gencell and by a grant from the Volkswagen Foundation (Priority program
      "conformational control") to M.F. We thank M. Blind, G. Mayer, D. Proske, and G.
      Sengle (Universitat Bonn) for helpful discussions as well as J. Crouzet, J. F.
      Mayaux, and M. Finer (Aventis Gencell) for support. 

PMID- 11592181
TI  - A Large 24-Membered-Ring Germanate Zeolite-Type Open-Framework Structure with
      Three-Dimensional Intersecting Channels This work was supported by the NSF of
      China (Grant No. 29873012 and 29925309), National Education Ministry, State Key
      Basic Research Program of PRC (G2000048001) Shanghai Science Foundation, and the
      Key Laboratory of Inorganic Hydrothermal Synthesis, Jilin University. We thank
      Prof. S. Feng and Dr. Z. Shi for invaluable discussions. 

PMID- 11592182
TI  - Chameleon States: High-Valent Metal-Oxo Species of Cytochrome P450 and Its
      Ruthenium Analogue The research in HU was sponsored by the Binational German
      Israeli Foundation (GIF) and by the Israeli Ministry of Science, Culture and
      Sport. Partial support by the US National Science Foundation (CHE-9814301) to
      J.T.G. is acknowledged. F.O. thanks the EU for a Marie Curie Fellowship. 

PMID- 11592183
TI  - Carbohydrate-Based Antibiotics: A New Approach to Tackling the Problem of
      Resistance.
AB  - Recent interest in the problem of antibiotic resistance has led to the
      identification of new targets and strategies for antibiotic discovery. Among
      these efforts, the development of small molecules as antibiotics to target
      carbohydrate receptors or carbohydrate-modifying enzymes represents a new
      direction. This review covers recent work in this regard and discusses the impact
      of each strategy on the development of drug resistance. Particularly interesting
      targets include unique cell-surface carbohydrates, the transglycosylase involved
      in peptidoglycan biosynthesis, and bacterial RNA. With a greater understanding of
      the genome of different bacteria as well as advances in functional genomics and
      proteomics, we can expect the discovery of a variety of targets for the
      development of novel antibiotics.

PMID- 11592184
TI  - "Non-VSEPR" Structures and Bonding in d(0) Systems.
AB  - Under certain circumstances, metal complexes with a formal d(0) electronic
      configuration may exhibit structures that violate the traditional structure
      models, such as the VSEPR concept or simple ionic pictures. Some examples of such
      behavior, such as the bent gas-phase structures of some alkaline earth dihalides,
      or the trigonal prismatic coordination of some early transition metal
      chalcogenides or pnictides, have been known for a long time. However, the number
      of molecular examples for "non-VSEPR" structures has increased dramatically
      during the past decade, in particular in the realm of organometallic chemistry.
      At the same time, various theoretical models have been discussed, sometimes
      controversially, to explain the observed, unusual structures. Many d(0) systems
      are important in homogeneous and heterogeneous catalysis, biocatalysis (e.g.
      molybdenum or tungsten enzymes), or materials science (e.g. ferroelectric
      perovskites or zirconia). Moreover, their electronic structure without formally
      nonbonding d orbitals makes them unique starting points for a general
      understanding of structure, bonding, and reactivity of transition metal
      compounds. Here we attempt to provide a comprehensive view, both of the types of
      deviations of d(0) and related complexes from regular coordination arrangements,
      and of the theoretical framework that allows their rationalization. Many
      computational and experimental examples are provided, with an emphasis on
      homoleptic mononuclear complexes. Then the factors that control the structures
      are discussed in detail. They are a) metal d orbital participation in sigma
      bonding, b) polarization of the outermost core shells, c) ligand repulsion, and
      d) pi bonding. Suggestions are made as to which of the factors are the dominant
      ones in certain situations. In heteroleptic complexes, the competition of sigma
      and pi bonding of the various ligands controls the structures in a complicated
      fashion. Some guidelines are provided that should help to better understand the
      interrelations. Bent's rule is of only very limited use in these types of
      systems, because of the paramount influence of pi bonding. Finally, computed and
      measured structures of multinuclear complexes are discussed, including possible
      consequences for the properties of bulk solids.

PMID- 11592185
TI  - Catalytic Allylic Oxidation of Alkenes Using an Asymmetric Kharasch-Sosnovsky
      Reaction.
AB  - Kharasch and Sosnovsky reported the allylic oxidation of alkenes to give racemic
      allylic benzoates. This could be achieved efficiently using a tert-butyl perester
      as the oxidant, in the presence of a copper or cobalt salt. The use of C(2)
      symmetric bis(oxazoline) ligands in the presence of copper(I) triflate with
      cyclic olefinic substrates gave the first synthetically useful asymmetric
      variant. The enantioselective control was good (up to 84 % ee) although yields
      were variable. In all cases the facial preference of the newly formed C-O bond
      was the same giving an S configuration at the allylic stereocenter. Lower
      stereocontrol was observed for large-ring alkenes and substantially reduced
      enantioselectivities were found with open-chain alkenes. This reaction has been
      further screened using a variety bis(oxazoline) and proline-derived ligands,
      which give a direct correlation between the chirality of the ligand and the
      enantioselectivity obtained. Individual substrates were found to be extremely
      sensitive to both the ligand structure and copper salt used as well as the
      presence of additives such as zinc, hydrazine, and molecular sieves.

PMID- 11592186
TI  - Encapsulated, Sandwiched, or Sticking Out: Closed-Shell Interactions of d(10)
      Metal Centers with Thallium(I).

PMID- 11592187
TI  - [Al(15)(&mgr;(3)-O)(4)(&mgr;(3)-OH)(6)(&mgr;-OH)(14)(hpdta)(4)](3-)-A New Al(15)
      Aggregate Which Forms a Supramolecular Zeotype
      H(5)hpdta=HOCH(2)[CH(2)N(CH(2)COOH)(2)](2). 

PMID- 11592188
TI  - Noyori's Hydrogenation Catalyst Needs a Lewis Acid Cocatalyst for High Activity
      We thank Mr. Christian Dambouwy, Thales Technologies AG, Zurich, Switzerland, for
      experimental work to compare the effects of various combinations of bases and
      salts. Additionally, we thank Mr. Holgar Sellner in the group of Prof. D. Seebach
      for assistance in ee measurements, and Sebastian D. Friess for carefully
      correcting the German version of this manuscript. 

PMID- 11592189
TI  - Bioreduction of AuCl(4)(-) Ions by the Fungus, Verticillium sp. and Surface
      Trapping of the Gold Nanoparticles Formed D.M. and S.S. thank the Council of
      Scientific and Industrial Research (CSIR), Government of India, for financial
      assistance. 

PMID- 11592190
TI  - Directed Evolution of an Enantioselective Enzyme through Combinatorial Multiple
      Cassette Mutagenesis.

PMID- 11592191
TI  - Superparamagnetic Triblock Copolymer/Fe(2)O(3) Hybrid Nanofibers NSERC of Canada
      is acknowledged for sponsoring this research. Dr. R. Yamdagni and Ms. Q. Wu are
      thanked for help with the use of their NMR magnet. Dr. Zhao Li is thanked for
      performing the TGA analysis. G.L. thanks the NSF of China for a distinguished
      Young Investigator's grant. 

PMID- 11592192
TI  - Thermally Stable Homogeneous Catalysts for Alkane Dehydrogenation S.O. thanks the
      German Academic Exchange Service (DAAD) for financing a research stay with W.C.K.
      in the USA. This work was supported by the National Science Foundation (CHE
      9800184 to M.B.H.), by the University of California Energy Institute and
      University of California Santa Barbara (to W.C.K.), and by the German Research
      Association (DFG, to M.W.H). We thank Dr. R. Mynott and Mrs. C. Wirtz, MPI fur
      Kohlenforschung, for NMR spectroscopic investigations. 

PMID- 11592193
TI  - Nickel-Catalyzed Homoallylation of Aldehydes in the Presence of Water and
      Alcohols We thank Mr. Y. Ohhama, NMR Facility, for his outstanding technical
      assistance. Financial support from the Ministry of Education, Science, Sports,
      and Culture, Japanese Government, Grant-in-Aid for Scientific Research B, is
      acknowledged. 

PMID- 11592194
TI  - High-Resolution NMR Spectroscopy of the beta-Amyloid(1-28) Fibril Typical for
      Alzheimer's Disease.

PMID- 11592195
TI  - A Demonstration of Anion Templation and Selectivity in Pseudorotaxane Formation
      We thank the EPSRC and the University of Reading for funds for the Image Plate
      System and the Natural Sciences and Engineering Research Council of Canada for
      financial support to Dr. Wisner. 

PMID- 11592196
TI  - Practical Approach to the Meerwein-Ponndorf-Verley Reduction of Carbonyl
      Substrates with New Aluminum Catalysts This work was partially supported by a
      Grant-in-Aid for Scientific Research from the Ministry of Education, Culture,
      Sports, Science and Technology, Japan. 

PMID- 11592197
TI  - Novel Three-Component Coupling Using Aluminum Tris(2,6-diphenylphenoxide) (ATPH):
      The Same Synthetic Strategy Leads to trans- and cis-Jasmonates.

PMID- 11592198
TI  - The First Platinum Formyl, a Member of a Series of Hexanuclear Clusters
      Exhibiting a Rare Structure We thank the Ministero dell'Universita e della
      Ricerca Scientifica e Tecnologica (MURST), Programmi di Interesse Nazionale, 2000
      2001, for financial support. 

PMID- 11592199
TI  - Short Hydrogen Bonds, Circular Dichroism, and Over-Estimates of Peptide Helicity
      We thank BBSRC for financial support (grant 42/B1524). 

PMID- 11592200
TI  - Orientation Dependence of Energy Transfer in an Anthracene-Porphyrin Donor
      Acceptor System This work was supported by CSIR and DST (New Delhi, India). We
      thank Dr. T. P. Radhakrishnan for many helpful discussions. 

PMID- 11592201
TI  - Design and Synthesis of a Protein Catenane This work was supported by The Skaggs
      Institute for Chemical Biology, The Sloan Foundation, and NIH-GM570132 (PED). We
      thank Dr. Songpong Deechongkit for assistance with the analytical ultracentrifuge
      and CD measurements. 

PMID- 11592202
TI  - A Highly Efficient Chain-Extension Process in the Systematic Syntheses of
      Carotenoid Natural Products This work was supported by the RRC program of MOST
      and KOSEF. 

PMID- 11592203
TI  - Dehydrogenation of [{(silox)(3)Nb}(2)(eta-1,2;eta-5,6-C(8)H(8))]
      (silox=tBu(3)SiO) to [{(silox)(3)Nb}(2)(eta-1,2;eta-5,6-C(8)H(6))] and Its
      Subsequent Alkene-to-Alkylidene Rearrangement We thank the US National Science
      Foundation for support of this research. 

PMID- 11592204
TI  - Enantioselective Total Synthesis of the Cyclophilin-Binding Immunosuppressive
      Agent Sanglifehrin A This work was financially supported by Eli Lilly and Company
      and a Robert Mayer Graduate Fellowship (to M.D.). We thank Prof. K. C. Nicolaou
      for providing authentic spectra of 1. 

PMID- 11592205
TI  - Rational Design and X-ray Molecular Structure of the First Irido-Cryptand and
      Encapsulation of a Tetrafluoroborate Anion The CNRS and UPMC are gratefully
      acknowledged for supporting this work. We thank Prof. D. Davoust and Dr. E.
      Condamine (IRCOF-Universite de Rouen, France) for carrying out the special
      (13)C{(19)F} NMR experiments on a 600 MHz Bruker instrument equipped with a TXO
      probe (13)C/(19)F,(1)H. 

PMID- 11592206
TI  - High Turnover Numbers for the Catalytic Selective Epoxidation of Alkenes with 1
      atm of Molecular Oxygen We acknowledge T. Hayashi (The University of Tokyo), M.
      Wada (Nippon Shokubai Co., Ltd.), and Y. Sumita (Nippon Shokubai Co., Ltd.) for
      their help with experiments. This work was supported in part by a Grant-in-Aid
      for Scientific Research from the Ministry of Education, Science, Sports and
      Culture of Japan. 

PMID- 11592207
TI  - Cleavage of the C(alkyl)-C(aryl) Bond of [Pd-CH(2)CMe(2)Ph] Complexes This work
      was supported by the Direccion General de Ensenanza Superior e Investigacion
      Cientifica (Project 1FD97-0919), the Ministerio de Educacion y Ciencia (PFPI
      grant to D. del Rio), and the Junta de Andalucia. J. A. L. thanks the CONACYT and
      the University of Guanajuato (Mexico) for a fellowship. 

PMID- 11592208
TI  - A Readily Available, Highly Potent E-Selectin Antagonist.

PMID- 11592209
TI  - Acids and Bases in One Pot while Avoiding Their Mutual Destruction We gratefully
      acknowledge support from the Israel Science Foundation (grant 96-98-2) and from
      the Infrastructure (Tashtiot) Project of the Israel Ministry for Science, Arts
      and Sports; and from the German-Israeli Foundation for Scientific Research and
      Development (Grant No. I-530.045.05/97). 

PMID- 11592210
TI  - Photonic Transduction of a Three-State Electronic Memory and of Electrochemical
      Sensing of NADH by Using Surface Plasmon Resonance Spectroscopy This study is
      supported by the Israel Science Foundation administered by The Israel Academy of
      Sciences and Humanities. NADH=1,4-dihydronicotinamide adenine dinucleotide. 

PMID- 11592212
TI  - Unichemo Protection: A Concept for Chemical Synthesis This work was supported by
      the Danish National Research Foundation. 

PMID- 11592211
TI  - Convergent Synthesis of Digitoxin: Stereoselective Synthesis and Glycosylation of
      the Digoxin Trisaccharide Glycal This research was supported by the U.S. National
      Institutes of Health (CA-59703). F.E.M. also thanks Novartis Pharmaceuticals for
      unrestricted additional funding (Grant Program for the Support of Academic
      Research in Synthetic Organic Chemistry). 

PMID- 11592213
TI  - An Asymmetric Synthesis of C-2-epi-Hygromycin A We thank the National Science
      Foundation and the National Institute of Health, General Medical Sciences, for
      their generous support of our programs. O.D. thanks the Association pour la
      Recherche contre le Cancer (ARC) for a postdoctoral fellowship. Mass spectra were
      kindly provided by the Mass Spectrometry Facility, University of San Francisco,
      supported by the NIH Division of Research Resources.

PMID- 11592214
TI  - Supramolecular Hydrogen-Bonded Oligo(p-phenylene vinylene) Polymers This work was
      supported by Netherlands Organization for Scientific Research (NWO) and the Royal
      Netherlands Academy of Arts and Sciences. The authors thank Michel Fransen for
      the synthesis of the starting materials, Joost van Dongen and Xiamwen Lou for
      matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MS
      measurements, Pascal Jonkheijm for atomic force microsopy (AFM) measurements, and
      Dr. Rint Sijbesma for fruitful and helpful discussions. Prof. Dr. Jan C. Hummelen
      is acknowledged for a generous gift of phenyl-[6,6]-C(61)-butyric acid methyl
      ester (PCBM). 

PMID- 11592215
TI  - Synthesis of the (+)-C26-C40 Domain of the Azaspiracids by a Novel Double
      Intramolecular Hetero-Michael Addition Strategy This work was supported by the
      United States National Institute of Environmental Health Sciences (NIEHS; grant
      number ES10615), NIH, and by Bristol-Myers Squibb (CJF). Its contents are solely
      the responsibility of the authors and do not necessarily represent the official
      views of the NIEHS, NIH, or BMS. We thank Dr. A. B. Dounay and Dr. G. Florence
      for critical reading of the manuscript. 

PMID- 11592216
TI  - Total Synthesis of Fostriecin (CI-920) We thank Professor Andrew G. Myers and
      Scott E. Schaus for helpful discussions, and Dr. Alexandra E. Gould and Isabel K.
      Reichardt for important preliminary experimental work. We also thank Dr. Robert
      J. Schultz of the Drug Synthesis and Chemistry Branch, Developmental Therapeutics
      Program, Division of Cancer Treatment and Diagnosis, National Cancer institute,
      for a sample of natural fostriecin. This work was supported by the NIH (GM
      59316), and by Beinecke Memorial and NSF predoctoral fellowships to D.E.C. 

PMID- 11592217
TI  - A Practical and Green Chemical Process: Fluoroalkyldistannoxane-Catalyzed
      Biphasic Transesterification.

PMID- 11592218
TI  - A Mild and Effective Method for the Transesterification of Carboxylic Acid Esters
      P.B. and R.M. are grateful to the Land Baden-Wurttemberg for a scholarship from
      the Landesgraduiertenforderung. 

PMID- 11592219
TI  - Total Synthesis of Hamigerans: Part 1. Development of Synthetic Technology for
      the Construction of Benzannulated Polycyclic Systems by the Intramolecular
      Trapping of Photogenerated Hydroxy-o-quinodimethanes and Synthesis of Key
      Building Blocks This work was financially supported by the National Institutes of
      Health (USA) and The Skaggs Institute for Chemical Biology, and grants from
      Abbott, Amgen, ArrayBiopharma, Boehringer-Ingelheim, Glaxo, Hoffmann-La Roche,
      DuPont, Merck, Pfizer, and Schering Plough. 

PMID- 11592220
TI  - Total Synthesis of Hamigerans: Part 2. Implementation of the Intramolecular Diels
      Alder Trapping of Photochemically Generated Hydroxy-o-quinodimethanes; Strategy
      and Completion of the Synthesis This work was financially supported by the
      National Institutes of Health (USA) and The Skaggs Institute for Chemical
      Biology, and grants from Abbott, Amgen, ArrayBiopharma, Boehringer-Ingelheim,
      Glaxo, Hoffmann-La Roche, DuPont, Merck, Pfizer, and Schering Plough. 

PMID- 11592221
TI  - The Influence of Excess Ammonia on the Mechanism of the Reaction of Boron
      Trichloride with Ammonia-An Ab Initio Molecular Dynamics Study This work was
      supported by the Deutsche Forschungsgemeinschaft in the framework of the
      Sonderforschungsbereich 408 "Anorganische Festkorper ohne Translationssymmetrie".
      We thank Mauro Boero from the Joint Research Center for Atom Technology, Tsukuba
      (Japan) for the reoptimization of the Martins-Troullier pseudopotentials for
      boron and chlorine, as well as the John-von-Neumann-Institut fur Computing,
      Julich, for making computer time available to us. 

PMID- 11592222
TI  - DNA-Directed Functionalization of Colloidal Gold with Proteins This work was
      supported by Deutsche Forschungsgemeinschaft and Fonds der Chemischen Industrie.
      We thank Prof. D. Blohm for helpful discussions and generous support. 

PMID- 11592223
TI  - The Unusual Formation of Iron Silicide by Reaction of Iron with SiCl(4) This work
      was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
      Industrie. We thank Dr. Kopke, Institut fur Mineralogie, Universitat Hannover,
      for the microprobe analyses. 

PMID- 11592224
TI  - Gold Pentafluoride: Structure and Fluoride Ion Affinity This work was supported
      by the Deutsche Forschungsgemeinschaft and the Fond der Chemischen Industrie. 

PMID- 11592225
TI  - DNA Polymerase Selectivity: Sugar Interactions Monitored with High-Fidelity
      Nucleotides This work was supported by a grant from the Deutsche
      Forschungsgemeinschaft. We thank Professor Dr. Michael Famulok for his continuing
      support. 

PMID- 11592226
TI  - The Azatriquinenamine Trimer-A Novel Proton Chelate Azatriquinanes, Part 3. This
      work was financially supported by the University of Nottingham and the Polish
      State Committee for Scientific Research (grant DS/8231-4-0097-1). We also thank
      the EPSRC National Crystallography Service, University of Southampton, for data
      collection. Part 2: Ref [4]. 

PMID- 11592227
TI  - Web Site: How To Find Your Way in a Metabolic Network.

PMID- 11592228
TI  - Treatment of early stage squamous-cell carcinoma of the glottic larynx:
      endoscopic surgery or cricohyoidoepiglottopexy versus radiotherapy.
AB  - BACKGROUND: Both surgery and radiotherapy are recognized treatments of T1-T2
      squamous cell carcinoma of the larynx. We retrospectively analyze and compare the
      oncological outcome of patients treated in a single institution, either by
      endoscopic surgery or partial supracricoid laryngectomy versus radiation therapy.
      METHODS: The medical records of 156 patients treated between 1983 and 1996 with
      either surgery (n = 75) or radiotherapy (n = 81) were reviewed. Male to female
      ratio, median age, and T-stage distribution were comparable. RESULTS: With a
      median follow-up time of 59 months, the 5-year cause-specific survival rate of
      93% was identical for both groups. The actuarial incidence of metachronous second
      primaries was 7% at 5 years. Local control at 5 years remained 84% after surgery
      and 77% after radiotherapy. Anterior commissure infiltration was shown to
      represent a negative predictive factor of local control for radiotherapy (p
      =.01). Salvage treatment brought ultimate local control to 96% of patients after
      surgery and 94% after radiation therapy with long-term laryngeal preservation
      rate altered significantly (p =.05) in the group of patients who received
      radiotherapy (90.1% vs 97.4%). CONCLUSION: The treatment of laryngeal cancer is
      always a compromise between oncological efficiency and preservation of function.
      Our data suggest that, assuming proper selection of patients, radiation therapy
      and surgery yield similar local control and survival rates. The functional
      disadvantages after surgery are moderate and clearly counterbalanced by a
      significant decrease in long-term laryngeal preservation rate after
      radiotherapeutic treatment.

PMID- 11592229
TI  - Management of advanced mandibular osteoradionecrosis with free flap
      reconstruction.
AB  - BACKGROUND: The purpose of this study was to assess the effectiveness of free
      tissue transfer for treatment of advanced mandibular osteoradionecrosis (ORN) in
      head and neck cancer patients. METHODS: We reviewed 29 patients who were treated
      for advanced mandibular ORN by radical resection and reconstruction with free
      flaps at our institution. All patients had either failed to respond to
      conservative treatment, including hyperbaric oxygen therapy and debridement or
      had pathological fracture due to ORN. RESULTS: Twenty-four vascularized bone (17
      fibula, five iliac, and two scapula), four rectus abdominis myocutaneous, and one
      radial forearm fasciocutaneous free flaps were used. The complications occurred
      in 6 of 29 patients (21%). A total of four flaps (14%) were lost. The mean follow
      up was 2 years 9 months. All patients had complete resolution of ORN symptoms. No
      evidence of ORN recurrence was observed in any patient. CONCLUSION: For advanced
      osteoradionecrosis of the mandible, radical resection followed by reconstruction
      using free flap provides a reliable means of obtaining good wound healing with
      acceptable aesthetic and functional results.

PMID- 11592230
TI  - Functional reconstruction of the lateral face after ablative tumor resection: use
      of free muscle and musculocutaneous flaps.
AB  - BACKGROUND: Wide resection of tumors of the middle third of the face often
      results in complex three-dimensional defects and facial paralysis either due to
      removal of the facial nerve within the tumoral tissue or to extensive resection
      of the facial muscles. METHODS: We report the cases of three patients who
      underwent wide excision of tumors of the cheek region, operations that resulted
      in tissue defects and facial palsy. Defect reconstruction and facial reanimation
      was accomplished in one stage through functional muscle transplantation. RESULTS:
      Follow-up of more than 1 year showed good symmetry at rest and reanimation of the
      corner of the mouth in all cases, but one patient, in which the ipsilateral
      facial main trunk was used as motor nerve supply to the transplanted muscle,
      developed significant muscle contracture and binding of the cheek skin.
      CONCLUSIONS: Every effort should be made to optimize the functional and cosmetic
      outcomes of neurovascular muscle transfers through precise planning and careful
      execution of the intricate details of the surgical technique for muscle
      transplantation.

PMID- 11592231
TI  - Preoperative magnetic resonance angiography in fibular-free flap reconstruction
      of head and neck defects.
AB  - BACKGROUND: Conventional angiography has been recommended for imaging of the leg
      prior to fibular-free flap harvest. Magnetic resonance angiography (MRA) offers a
      similar level of accuracy at no risk to the patient and at a lower cost. METHODS:
      Thirty-two patients who were considered for fibular-free flap were
      retrospectively reviewed. Preoperative MRA of the lower extremities was performed
      on all patients and used to evaluate vessel patency. The decision of free flap
      donor site was based upon MRA findings. RESULTS: The choice of side harvested was
      changed in four (12.5%) patients and the fibula was excluded as a donor site in
      three patients (9%). Flap design was altered in one patient found to have
      abnormally short peroneal arteries. The usual correlation between palpable distal
      pulses and proximal patent arteries was found to be unreliable. All 29 patients
      underwent successful free flap reconstruction with no ischemic complications.
      CONCLUSIONS: Preoperative MRA is useful when choosing the side of fibular
      harvesting and in excluding patients from the fibula as a donor site. We feel
      that the cost of obtaining preoperative imaging is outweighed by avoiding
      potential ischemic complications and additional operating room time with no risk
      to the patient's health.

PMID- 11592232
TI  - Loss of imprinting and loss of heterozygosity on 11p15.5 in head and neck
      squamous cell carcinomas.
AB  - BACKGROUND: IGF2 and H19 are reciprocal imprinted genes with paternal and
      maternal monoallelic expression, respectively. This is interesting, because IGF2
      is known as a growth factor, and H19 encodes a RNA with putative tumor suppressor
      action. Furthermore, IGF2 and H19 are linked genes located on chromosome 11p15.5,
      a common site of loss of heterozygosity in human cancers. METHODS: We performed
      an allelic-typing assay using a PCR-RFLP-based method for identification of
      heterozygous informative cases in head and neck squamous cell carcinomas. Tumoral
      total RNA was extracted from each of the heterozygotes and further studied by RT
      PCR analysis. RESULTS: We detected the expression of the IGF2 gene in 10 of 10
      informative cases. Two cases exhibited LOI of the IGF2 gene as evidenced by
      biallelic expression, and in another case, LOH was coupled with monoallelic
      expression of this growth factor. LOI for the H19 gene was observed in 1 of 14
      informative samples analyzed. In this case, we also detected parallel monoallelic
      expression of the IGF2 gene. Down-regulation of the H19 gene was observed in 10
      of 14 cases. CONCLUSION: These findings support the hypothesis that H19 may be a
      tumor suppressor gene involved in head and neck carcinogenesis. Furthermore, our
      data showed that genetic and epigenetic changes at 11p15.5 could lead to abnormal
      expression of imprinted genes in HNSCC.

PMID- 11592233
TI  - Nicotine affects the signaling of the death pathway, reducing the response of
      head and neck cancer cell lines to DNA damaging agents.
AB  - BACKGROUND: Growing evidence suggests that tobacco can affect the responsiveness
      of cancer cells to treatment, particularly those of head and neck cancer. This
      article describes the effects of nicotine on the signaling of the death pathway,
      resulting in a decreased cytotoxicity of various anticancer agents such as
      cisplatin and gamma-radiation. METHODS: Colony-forming assays (CFA), using the
      head and neck cancer cell lines UMSCC10b and UMSCC5 and DNA fragmentation assays,
      were used to determine the effect of nicotine on cytotoxicity of various
      anticancer agents, whereas PCR and a JNK activity test were used to study the
      effect of nicotine on message expression levels and activity of the JNK signaling
      pathway. RESULTS: Nicotine consistently reduced the cytotoxic effect of DNA
      damaging agents, such as cisplatin, UV, and gamma radiation, in UMSCC10b cells,
      increasing their IC(50) values by twofold, 1.7-fold, and 1.8-fold, respectively.
      These results were confirmed in a second squamous cell carcinoma cell line
      (UMSCC5), demonstrating an increase in IC(50) values for cDDP by twofold and 1.9
      fold in the UMSCC10b andUMSCC5, respectively. In addition, nicotine reduced the
      DNA fragmentation 48 h after cDDP exposure in UMSCC10b and UMSCC5 cell lines by
      30% and 33%, respectively. The latter, however, was not the result of an effect
      of nicotine on either the uptake of cDDP or repair of the cDDP-DNA-adducts. To
      further substantiate the adverse effect of nicotine, the JNK and gadd153
      signaling pathways were studied. JNK activity was decreased by 1.8-fold, as well
      as the expression of its downstream target c-jun (1.9-fold), when tumor cells
      were exposed to cisplatin in the presence of nicotine. In addition, the gadd153
      message was affected and reduced by 1.8-fold. CONCLUSIONS: Nicotine adversely
      affects the cytotoxicity of DNA-damaging agents. Nicotine does not interfere with
      the repair of the damage but directly affects the signaling of the death pathway,
      reducing the signaling of the JNK1 pathway. The latter results in a decrease in
      efficacy of the anticancer treatment in tumors exposed to nicotine.

PMID- 11592234
TI  - Improving the functional outcome of Tucker's reconstructive laryngectomy.
AB  - BACKGROUND: The goal of reconstructive laryngectomy addressing glottic carcinoma,
      as described by Tucker, is twofold: achieve local control and preserve as much as
      possible the physiological laryngeal function. METHODS: The study consisted of
      long-term assessment of oncological, deglutitory, and vocal outcome in 34
      patients following Tucker's reconstructive laryngectomy. Postoperative follow-up
      included fiberscopic examination, videoradiography, and voice assessment after
      speech rehabilitation. RESULTS: The 5-year overall survival rate was 92% +/- 5%.
      Fiberscopic examination and videoradiography contributed to observing and
      understanding the rehabilitation process and impairment to its progress. Two main
      compensatory movements were identified: the anticipatory backward movement of the
      tongue base (50%) and the anticipatory upward laryngeal motion (15%). Both
      movements occurred simultaneously at the beginning of the pharyngeal stage of the
      swallow (35%). The median duration prior to tracheostomy tube removal was 14
      days. Swallowing of solids resumed on day 9 (median), and liquid intake (water
      and soup) resumed on day 12 (median). The median duration of hospitalization was
      16 days. Following speech rehabilitation, the latest follow-up visit measured as
      follows: the mean conversational voice intensity at 64 dB (range, 57-79 dB); the
      mean maximum intensity at 87 dB (range, 78-96 dB); the minimum intensity at 54 dB
      (range, 45-65 dB); the mean maximum phonation time at 16 seconds (range, 10-29
      seconds); and the mean phonation quotient at 284 mL/second (range, 205-341
      mL/second). According to our classification, voice spectral analysis revealed 19
      class-III patients, 12 class-II patients, and three class-I patients. CONCLUSION:
      Tucker's reconstructive laryngectomy is reliable in terms of both the oncological
      and functional outcome. Fiberscopic examination and videoradiography are two
      complementary methods for assessing postoperative deglutition.

PMID- 11592235
TI  - The pectoralis major myocutaneous flap: Is the subclavicular route safe?
AB  - BACKGROUND: The pectoralis major myocutaneous flap has a proven track record as a
      reconstructive tool, but excessive bulk and a limited arc of rotation can be
      problematic. Although this can be addressed by passing the pedicle deep to the
      clavicle, some authors consider that this modification may compromise the flap.
      This prospective study therefore sought to compare the supraclavicular and
      subclavicular routes with particular emphasis on potential vascular sequelae.
      METHODS: One-hundred patients were randomly allocation into two groups. Following
      flap harvest, the pedicle was passed in either a supraclavicular or subclavicular
      plane depending upon allocation. The survival rate and complications of each flap
      were assessed at 1 month. RESULTS: Total flap necrosis occurred in three (7.0%)
      of the subclavicular flaps and two (3.5%) of the supraclavicular flaps. This
      difference was not significant (p =.77). Likewise no statistical difference was
      noted between the rates of partial flap necrosis, fistula formation infection, or
      secondary hemorrhage in either group. CONCLUSIONS: The subclavicular route
      addresses the problem of pectoralis major myocutaneous flap bulk and may increase
      the arc of rotation of the flap without significantly compromising its vascular
      supply.

PMID- 11592236
TI  - Significance and management of thyroid lesions in lymph nodes as an incidental
      finding during neck dissection.
AB  - BACKGROUND: The incidental discovery of thyroid lesions in lymph nodes during a
      lymph node dissection performed for a separate primary head and neck tumor is an
      unusual clinical entity. Its discovery has led to controversy regarding its
      significance and management. METHODS: We identified five patients over the years
      1991-1999 with this finding. All five patients were subsequently treated with a
      total thyroidectomy and a level VI lymph node dissection. RESULTS: Pathological
      examination revealed three papillary carcinomas and level VI lymph node
      metastases in the two patients who had carcinoma in their thyroid glands. All
      five patients are presently free of their primary and thyroid disease on follow
      up examinations. CONCLUSIONS: These patients should be addressed with additional
      work-up and surgery if metastatic thyroid cancer is documented in the lymph node.
      We offer a diagnostic algorithm that may aid in further work-up and treatment in
      these unusual cases.

PMID- 11592237
TI  - Prediction of depression 6 months to 3 years after treatment of head and neck
      cancer.
AB  - BACKGROUND: Head and neck cancer and its treatment can have important
      psychosocial implications. Many patients become depressed. The aim of this
      prospective study is to examine whether pretreatment variables can be used to
      predict depression up to 3 years after treatment. METHODS: Head and neck cancer
      patients (n = 197) treated with surgery and/or radiotherapy completed both before
      and after treatment a questionnaire including items on social support, coping,
      depressive symptoms, physical functioning, and physical symptoms. RESULTS: Eight
      pretreatment variables (tumor stage, sex, depressive symptoms, openness to
      discuss cancer in the family, available appraisal support, received emotional
      support, tumor-related symptoms, and size of the informal social network) were
      used to calculate a risk score to determine which patients were depressed at 6
      months to 3 years after treatment (positive predicted value, 58%; negative
      predicted value, 83%). CONCLUSIONS: Eight pretreatment variables can be used to
      predict accurately those head and neck cancer patients who are likely to become
      depressed up to 3 years after treatment.

PMID- 11592238
TI  - Characterization of a spontaneously arising murine squamous cell carcinoma (SCC
      VII) as a prerequisite for head and neck cancer immunotherapy.
AB  - BACKGROUND: To develop novel therapeutic approaches for patients with head and
      neck malignancies, poorly immunogenic murine models of squamous cell carcinoma
      (SCC) need to be defined. METHODS: The phenotype, growth characteristics, and
      responsiveness to tumor-specific T-cell transfer of a spontaneously arising
      murine SCC (SCC VII) were characterized. RESULTS: SCC VII expresses major
      histocompatibility complex (MHC) class I molecules yet is resistant to tumor
      specific T-cell killing and relatively insensitive to killing mediated by
      lymphokine-activated killer (LAK) cells. Intradermal tumors are reproducibly
      established after vaccination of 5 x 10(4) cells, and systemic micrometastases
      are apparent after intravenous administration of 2.5 x 10(4) cells. Immunotherapy
      of 3-day lung metastases using tumor-specific T cells and systemic interleukin-2
      (IL-2) was ineffective in reducing the number of metastases in vivo. CONCLUSIONS:
      SCC VII is a poorly immunogenic murine squamous cell cancer, which represents an
      ideal model for preclinical testing of immunotherapeutic approaches for patients
      with SCC of the upper aerodigestive tract.

PMID- 11592239
TI  - Surgical treatment of cervical node metastases from squamous carcinoma of the
      upper aerodigestive tract: evaluation of the evidence for modifications of neck
      dissection.
AB  - BACKGROUND: This review article examines the role of the different types of neck
      dissection in the treatment of squamous carcinoma metastases to the cervical
      nodes. METHODS: A critical evaluation of the literature on the pathologic basis,
      oncologic effectiveness, and functional outcome of neck dissection. RESULTS:
      Pathologic data show preferential metastasis to different lymph node levels, in
      N0- and N+-staged disease, depending on the primary tumor site. Comparative
      studies on control of regional metastases suggest that modified radical is no
      less effective than radical neck dissection, but there is insufficient data to
      draw firm conclusions on the role of selective neck dissection. Selective and
      modified radical dissections result in less shoulder disability than radical neck
      dissection. CONCLUSIONS: Modified radical neck dissection is supported by
      pathologic and clinical evidence in N1- and 2-staged disease. There may be a role
      for selective dissection, but there is a need for more information on oncologic
      outcome. Prospective multicenter systematic data collection on the outcome of
      neck dissection is a pragmatic alternative to a trial.

PMID- 11592240
TI  - Resurfacing of the nasopharynx after nasopharyngectomy using a free radial
      forearm flap.
AB  - BACKGROUND: Nasopharyngectomy is emerging as an important treatment option for
      salvaging locally recurrent nasopharyngeal carcinoma (NPC). After
      nasopharyngectomy, resurfacing the nasopharynx and covering the internal carotid
      artery is important to minimize the risk of infection, osteoradionecrosis, and
      carotid rupture. Previous authors have advocated the use of free grafts of skin
      and mucosa for this purpose but have also described significant rates of partial
      and total graft failure. METHODS: We believe that the best and most reliable way
      to resurface the nasopharynx is with vascularized tissue, and our preference is
      for the use of a free radial forearm flap. To illustrate our approach, we present
      two patients who underwent nasopharyngectomy by means of a maxillary swing
      approach and who had resurfacing of the surgical defect with a free radial
      forearm flap. RESULTS: Both patients had complete en bloc resection of tumor
      followed by the insetting of a free radial forearm flap to reline the surgical
      defect. Both flaps remained completely viable, and both patients achieved
      successful resurfacing of the entire nasopharynx. The morbidity of surgery was
      minimal, and there were no perioperative complications. On assessment 1 year
      later, the free radial forearm flap continues to reline the entire
      neonasopharynx, and the long-term functional recovery after surgery is excellent.
      CONCLUSION: Resurfacing the nasopharynx after nasopharyngectomy with a free
      radial forearm flap aids healing and minimizes the risk of complications. The
      morbidity of surgery is minimal and the functional recovery is excellent.

PMID- 11592241
TI  - Functions of vitamins beyond recommended dietary allowances. Proceedings of a
      European Academy of Nutritional Sciences workshop. 1997, Nice, France.

PMID- 11592242
TI  - Editorial comment: Coronary artery disease and HIV infection--should we be
      concerned?

PMID- 11592244
TI  - Editorial comment: Factitious HIV syndrome-back to basics in diagnosis.

PMID- 11592243
TI  - Editorial comment: Perinatal trials and prophylaxis decision making in 2001.

PMID- 11592245
TI  - Hormones and cancer: new insights, new challenges.

PMID- 11592246
TI  - Gathering the big picture II.

PMID- 11592247
TI  - Is Canada's Medicare system sustainable? A review of recent policy
      recommendations.

PMID- 11592248
TI  - Letters of reference to remain confidential.

PMID- 11592249
TI  - Aramark profile. Lynda Cranston, Chief Executive Officer, Canadian Blood
      Services. Interview by Cynthia Martin.

PMID- 11592250
TI  - The editor interviews ... Kevin Keough, Chief Scientist, Health Canada. Interview
      by Dr. Peggy Leatt.

PMID- 11592251
TI  - The order of ventricular excitation in human bundle-branch block. 1932.

PMID- 11592252
TI  - 1st Congress of the DFG graduate seminar: Cell-cell Interaction in Reproduction,
      and 5th Dies Andrologicus. Marburg, Germany, 25 November 2000. Abstracts.

PMID- 11592253
TI  - Proceedings of the Symposium on Mass Spectrometric Methods of Trace Element
      Analysis, and 16th ICP-MS Users Meeting, 18-21 September 2000, Julich, Germany.
      Special issue dedicated to Professor Dr. Hans-Joachim Dietze on the occasion of
      his 65th birthday.

PMID- 11592254
TI  - Educate patients, cut return asthma visits.

PMID- 11592255
TI  - Comparative West Nile virus detection in organs of naturally infected American
      Crows (Corvus brachyrhynchos).
AB  - Widespread deaths of American Crows (Corvus brachyrhynchos)were associated with
      the 1999 outbreak of West Nile (WN) virus in the New York City region. We
      compared six organs from 20 crow carcasses as targets for WN virus detection.
      Half the carcasses had at least one positive test result for WN virus infection.
      The brain was the most sensitive test organ; it was the only positive organ for
      three of the positive crows. The sensitivity of crow organs as targets for WN
      virus detection makes crow death useful for WN virus surveillance.

PMID- 11592256
TI  - Nipah virus among military personnel involved in pig culling during an outbreak
      of encephalitis in Malaysia, 1998-1999.

PMID- 11592257
TI  - New AIDS cases, deaths hold steady: CDC report.

PMID- 11592258
TI  - AIDS vaccines show promise in primates.

PMID- 11592259
TI  - Once-daily venlafaxine extended release (XR) vs. fluoxetine for the treatment of
      depression.

PMID- 11592261
TI  - Anticholinergic poisoning secondary to custom medicine in Vanuatu.

PMID- 11592262
TI  - Why and when are seizures bad for the brain?

PMID- 11592263
TI  - The natural history of refractory idiopathic thrombocytopenic purpura.

PMID- 11592265
TI  - Complex aortic valve surgery: Introduction.

PMID- 11592264
TI  - Attribution of posttransplantation toxicity to methotrexate regarding genotype of
      methylenetetrahydrofolate reductase gene (MTHFR) polymorphism needs further
      clarification.

PMID- 11592266
TI  - Visual vignette: acanthosis nigricans.

PMID- 11592267
TI  - Elements of precaution: recommendations for the regulation of food biotechnology
      in Canada.

PMID- 11592269
TI  - XXVI Congress of the Society of Biomechanics. Marseille, France, 13-14 September
      2001. Abstracts.

PMID- 11592268
TI  - [Oxaliplatin (Eloxatin). Progress in cancer therapy].

PMID- 11592270
TI  - ACOG Committee Opinion. Guidelines for relationships with industry. Number 259,
      October 2001. (Replaces No. 182, April 1997).

PMID- 11592271
TI  - ACOG Committee Opinion. Circumcision. Number 260, October 2001.
AB  - The American College of Obstetricians and Gynecologists supports the current
      position of the American Academy of Pediatrics that finds the existing evidence
      insufficient to recommend routine neonatal circumcision. Given this circumstance,
      parents should be given accurate and impartial information to help them make an
      informed decision. There is ample evidence that newborns circumcised without
      analgesia experience pain and stress. If circumcision is performed, analgesia
      should be provided.

PMID- 11592272
TI  - ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical
      management guidelines for obstetrician-gynecologists. Number 31, October 2001.
      (Replaces Technical Bulletin number 206, June 1995; Committee Opinion number 172,
      May 1996; Committee Opinion number 187, September 1997; Committee Opinion number
      198, February 1998; and Committee Opinion number 251, January 2001).
AB  - Preterm birth is the second leading cause of neonatal mortality in the United
      States (1) (second only to birth defects), and preterm labor is the cause of most
      preterm births (2). Neonatal intensive care has improved the survival rate for
      babies at the cusp of viability, but it also has increased the proportion of
      survivors with disabilities. The incidence of multiple births also has increased
      along with the associated risk of preterm delivery (4). Interventions to delay
      preterm delivery in these settings have not shown conclusive effectiveness.
      Because the morbidity of babies born after 34-35 weeks of gestation has
      diminished, most efforts to identify preterm deliveries have focused on
      deliveries before this age. This document describes the various methods proposed
      for predicting preterm birth and the evidence for their roles in clinical
      practice.

PMID- 11592273
TI  - Congress of Nephrology 2001. Joint scientific meeting of the Gesellschaft fur
      Nephrologie and the Deutsche Arbeitsgemeinschaft fur Klinische Nephrologie.
      September 29-October 2, 2001. Abstracts.

PMID- 11592274
TI  - Abstracts of the 33rd Nordic Meeting of Gastroenterology, 24th Meeting of
      Endoscopy, 12th Nordic Meeting of Gastrointestinal Motility, and the Annual
      Endoscopy/Gastroenterology Nurses'/Assistants' Meeting. Reykjavik, Iceland, 9-12
      June 2001.

PMID- 11592275
TI  - Society for In Vitro Biology membership directory 1999-2000.

PMID- 11592276
TI  - [Ultraschall 2001. 25th Three-country meeting of the Swiss, German, and Austrian
      Societies for Ultrasound in Medicine. 26-29 September 2001, Nurnberg. Abstracts].

PMID- 11592277
TI  - Abstracts of the 2000 and 2001 meetings of the Gesellschaft fur Biochemie und
      Molekularbiologie.

PMID- 11592278
TI  - Abstracts of the joint meeting of the Swiss Society of Pharmacology and
      Toxicology, the German Society for Experimental and Clinical Pharmacology and
      Toxicology, the Austrian Pharmacological Society. 1-2 October 20001, Berne,
      Switzerland.

PMID- 11592279
TI  - Pathological Society of Great Britain and Ireland 183rd meeting. 3-6 July 2001.
      Abstracts.

PMID- 11592280
TI  - Significant achievement awards: An integrated program of culture-sensitive health
      care for refugees and immigrants--the Mental Health Division of the Community
      University Health Care Center in Minneapolis.

PMID- 11592282
TI  - 18th European Congress of Pathology. Berlin, Germany, September 8-13, 2001.
      Abstracts.

PMID- 11592281
TI  - Significant achievement awards: A unique approach to mental health care for young
      children--the Multnomah County, Oregon, Early Childhood Mental Health Program.

PMID- 11592283
TI  - Reconstitution in lipid bilayer of smooth muscle cation channels activated
      through a GTP-binding protein.
AB  - Reconstitution of G-protein-coupled receptor activated cation channels into the
      lipid bilayer was attempted with plasma membrane vesicles prepared from guinea
      pig ileal smooth muscle using the purification technique previously applied to
      the large conductance Ca2+-dependent and ATP-sensitive K+ channels (Toro et al.,
      1990). Under Na+-rich conditions, incorporation of plasma membrane vesicles into
      the bilayer produced GTPgammaS (100 microM)-activatable channel activities that
      are inhibited by GDPbetaS (1 mM), sensitive to Ca2+ and enhanced by
      depolarization. The reversal potential and unitary conductance (tens of
      picosiemens) of these channels varied in a manner dependent on Na+ concentration,
      but not affected by Cl-. These results strongly indicate that the reconstituted
      channels activated by GTPgammaS belong to a class of voltage-dependent, Ca2+
      sensitive cation-selective channels that are activated through a G-protein, and
      correspond most likely to the muscarinic receptor-activated cation channels
      previously identified in the same preparation. These results also suggest
      potential usefulness of bilayer incorporation technique to investigate the
      receptor-operated cation channels in smooth muscle.

PMID- 11592284
TI  - Changes in Ca2+ signaling and contractile protein isoforms in smooth muscle cells
      from guinea pig ileum during culture.
AB  - Single smooth muscle cells (SMCs) isolated from guinea pig ileum using
      collagenase and papain were cultured on laminin-coated dishes in MEM containing
      fetal calf serum. Temporal changes in intracellular calcium ion concentration in
      response to carbachol and to ATP were investigated using fluo-3/AM and
      fluorescence microscopy. It was observed that carbachol caused an increased
      intracellular calcium ion in freshly isolated single SMCs but a reduced or
      negative response of cultured SMCs before confluence. On the other hand, ATP was
      observed to cause an increase in the calcium ion content of SMCs throughout the
      culture. SDS-PAGE and Western blot analyses revealed changes in the expression of
      contractile proteins as follows. l-Caldesmon and non-muscle type myosin heavy
      chain (NMHC) (considered to be marker molecules for dedifferentiation in smooth
      muscle cells) and non-muscle type tropomyosin were not observed in freshly
      isolated single SMCs. l-Caldesmon and NMHC appeared in the cultured SMCs within 2
      days and the tropomyosin isoform was observed 6 days following seeding.
      Simultaneously, smooth muscle type myosin heavy chain (SMHC) decreased strikingly
      and the 41 kDa tropomyosin monomer was lost. The content of alpha-actin decreased
      gradually to a minimum on day 6 when non-muscle type tropomyosin appeared, and
      the cells began to proliferate rapidly. These results suggest that the loss of
      contractility in cultured smooth muscle cells is more closely related to changes
      in contractile protein profiles than to receptor-mediated signal transduction and
      that in addition to NMHC and l-caldesmon, non-muscle type tropomyosin may be
      useful as a marker molecule for de-differentiation of smooth muscle cells.

PMID- 11592286
TI  - [Abstracts of the XXXI Congress of the Spanish Society of Nephrology. 29
      September-3 October 2001, Zaragoza].

PMID- 11592285
TI  - Hypertension and impairment of endothelium-dependent relaxation of arteries from
      spontaneously hypertensive and L-NAME-treated Wistar rats.
AB  - Effects of chronic treatment of normotensive Wistar rats with N(omega)-nitro-L
      arginine methyl ester (L-NAME) on blood pressure and on endothelium-dependent
      relaxation of the aorta, carotid and iliac arteries were studied. The endothelium
      dependent relaxation was compared in arteries from normotensive Wistar Kyoto rats
      (WKY) and genetically hypertensive rats (stroke-prone spontaneously hypertensive
      rats, SHRSP). Chronic treatment of normotensive Wistar rats with L-NAME caused an
      elevation of blood pressure. The elevated blood pressure at 15 weeks of age was
      significantly higher in these animals than that of untreated Wistar rats, but
      lower than that of SHRSP. Endothelium-dependent relaxation of the arteries
      induced by acetylcholine (ACh) was almost abolished by chronic treatment with L
      NAME. The remaining small relaxation in arteries from L-NAME-treated rats was
      completely inhibited by application of L-NAME (10(-4) M). In such preparations,
      higher concentrations of ACh induced a contraction, which was abolished by
      removal of the endothelium or by an application of indomethacin (10(-5) M).
      Endothelium-independent relaxation induced by sodium nitroprusside was similar
      between preparations from untreated and L-NAME-treated Wistar rats. Endothelium
      dependent relaxation was significantly impaired in preparations from SHRSP, when
      compared with that in those from WKY. However, the impairment was less prominent
      in preparations from SHRSP than in those from L-NAME-treated rats. These results
      suggest that the impairment of endothelium-dependent relaxation in the arteries
      from L-NAME-treated rats is not due to the elevated blood pressure resulting from
      the chronic treatment, and that impairment of NO synthesis by the endothelium
      does not play a major role in the initiation of hypertension in SHRSP.

PMID- 11592287
TI  - Abstracts of the American College of Rheumatology 65th meeting and the
      Association of Rheumatology Health Professionals 36th meeting. November 10-15,
      2001. San Francisco, California, USA.

PMID- 11592288
TI  - Texas Dental Association 2001-2002 directory of members.

PMID- 11592289
TI  - IXth Congress of the European Society for the Study and Prevention of Infant
      Death. Prenatal health care and postnatal development. Istanbul, Turkey, 2-6
      October 2001. Abstracts.

PMID- 11592290
TI  - American Society for Gravitational and Space Biology Fourth Annual Meeting.
      October 20-23, 1988, Grand Hyatt Hotel, Washington, D.C. Program and abstracts.

PMID- 11592291
TI  - Evolution of French programs in the space life sciences.

PMID- 11592292
TI  - Plans and future directions of the German life sciences program.
AB  - The German life sciences program covers three disciplines: 1) medicine, 2)
      biology, and 3) biological processing. The overall objectives are to acquire
      expertise in manned flight techniques and to enable scientists to conduct
      qualified scientific research by use of the specific space environment. To
      achieve these goals the German government provides the scientific community with
      national and international flight opportunities.

PMID- 11592293
TI  - International cooperation in the field of space life sciences: European Space
      Agency's (ESA) perspectives.
AB  - International cooperation in life sciences, as in any other of the space research
      fields, takes place at two distinct levels: scientist to scientist, or agency to
      agency. This article is more concerned with the agency to agency level, which
      involves the arrangements made between two partners for the flying of experiments
      and/or hardware on space missions. International cooperation is inherent to the
      European Space Agency (ESA), since it consists of 13 member states (Austria,
      Belgium, Denmark, France, Ireland, Italy, the Netherlands, Norway, Spain, Sweden,
      Switzerland, United Kingdom, and West Germany) and one associated member,
      Finland. ESA also has special cooperative arrangements with Canada. Life sciences
      research in ESA is carried out within the Microgravity Research Program, an
      optional program to which member states (in this case all but Austria and
      Ireland) contribute "a la carte," and receive their "share" accordingly.
      Therefore, many of the activities are naturally linked to international
      arrangements within the member states, and also to arrangements between the
      agencies, with life sciences being the dominant activity between NASA and ESA.

PMID- 11592294
TI  - Future prospects for space life sciences from a NASA perspective.
AB  - As the U.S. Space Program lifted off the ground again on September 29, 1988,
      along with it came the return of scientific possibilities for the U.S. space
      science community. The end of that mission, STS-26, marked a new beginning for
      NASA. The success of STS-26 was critical to the dreams and careers of many
      people. Many of those dreams had been put on hold and, in fact, were fading as
      the U.S. watched the rest of the world move ahead rapidly with attempts to gain
      access to the limited and precious laboratory of space.

PMID- 11592295
TI  - Analysis of pharyngeal swallowing in healthy subjects.
AB  - The Biomechanics of pharyngeal swallowing was investigated by videofluorography
      in 10 healthy subjects (9 men and 1 woman) during swallowing of 3 ml of fluid
      contrast medium and a small spoonful of jelly contrast medium. The items measured
      were the sequential movement of the hyoid bone: hyoid bone angle; epiglottis
      angle: antero-posterior diameters of the thyroid cartilage, larynx, hypopharynx,
      and pharyngoesophageal junction: and transport time of the swallowed bolus. It
      was concluded that the movement of the hyoid bone and thyroid cartilage and the
      angle of the epiglottis were important for evaluation of pharyngeal swallowing,
      and that the antero-posterior and vertical movement of the hyoid bone showed a
      significant relationship to transport time of the swallowed bolus as far as the
      esophagus, which was within 400 msec on average.

PMID- 11592296
TI  - Extra-articular avulsion fracture of the distal phalanx of the ring finger--a
      case report.
AB  - This report describes a rare case of extra-articular avulsion fracture of the
      flexor digitorum profundus tendon in a 59-year-old man is reported. A large
      avulsed fragment of bone was localized by radiography on the volar side of the
      middle phalanx. The avulsed bone fragment had torn the A4 pulley and had been
      caught by the C2 pulley. The fracture was extra-articular. The avulsed fragment
      was fixed using a fragment fixation screw. This case was classified as a subtype
      of type 3 according to Leddy's classification. Only 10 cases of type 3 injury
      have been reported, and none of them clearly involved an extra-articular
      fracture.

PMID- 11592297
TI  - Preliminary study for sentinel lymph node identification with Tc-99m tin colloid
      in patients with esophageal or gastric cancer.
AB  - The purpose of this study is to determine whether a lymph node identified with
      high radioisotope (RI) activity is a sentinel node. We studied 26 patients with
      either esophageal or gastric cancer whose preoperative imaging studies showed no
      lymph node metastasis. Before surgery, Tc-99m tin colloid was injected via
      endoscopy into the submucosa. In lymph nodes dissected at surgery, RI activity
      was measured by a scintillation counter, and metastatic status was examined by
      hematoxylin-eosin staining. The number of dissected nodes was 45 +/- 15 (mean +/-
      SD) per patient, and the number of nodes with high RI activity was 4 +/- 1. Nodal
      metastasis occurred in 11 of 26 patients. In 9 of these 11 patients, metastatic
      foci were found in one or more nodes with high RI activity. In one of the 2
      remaining patients, endoscopic clipping was applied just above the injection
      sites, and in the other patient, the tumor invasion was beyond the muscle layer.
      For further analysis, the case with clipping was excluded, and only those in
      which the tumor invasion was confined within the muscle layer were evaluated. Six
      of 18 patients in this analysis showed nodal metastasis. Each of the 6 patients
      had at least one node that showed high RI activity and that was positive for
      metastasis. We conclude that when tumor invasion remains within the muscle layer,
      lymph nodes with high RI activity can be regarded as sentinel nodes.

PMID- 11592298
TI  - Tsutsugamushi disease in Kanagawa Prefecture, Japan: clinical report of two cases
      and survey of other incidences in 1998.
AB  - Tsutsugamushi disease is characterized by the early appearance of a black crust
      at the bitten area and the subsequent development of macular or macropapular rush
      on the whole body with high fever. While treatment with tetracycline derivatives
      and chloramphenicols is effective, delayed diagnosis or inappropriate treatment
      will lead to fatality. In this report, we describe two typical cases of
      tsutsugamushi disease and discuss other incidences in Kanagawa Prefecture, Japan,
      in 1998. One of the present two patients was diagnosed to be a case of the new
      type by Kawasaki strain of Rickettsia tsutsugamushi, while responsible strain was
      not identified for the other case. Since the disease is spreading widely even to
      suburban areas, we emphasize the need to consider the possible diagnosis of
      tsutsugamushi disease in patients with generalized eruption and high fever.

PMID- 11592299
TI  - NADH-dependent dehydroascorbate reductase in the rabbit lens.
AB  - The present investigation demonstrates the existence of NADH-dependent
      dehydroascorbate (DHA) reductase activity in the soluble fraction of the rabbit
      lens. This DHA reductase was specific for NADH, and its apparent Km values for
      DHA and NADH were 5.7 mM and 4.0 microM, respectively. In a gel filtration of the
      lens soluble fraction on a Sephadex G-75 superfine column, the NADH-dependent DHA
      reductase activity was eluted at the oligomeric betaL1-crystallin fraction, which
      may also contain lambda-crystallin (a rabbit-specific crystallin). Furthermore,
      about 80% of protein fractions separated from the betaL1-crystallin fraction by
      DEAE-cellulose ion-exchange column chromatography exhibited DHA reductase
      activity. In the SDS-PAGE analysis of the protein fractions with DHA reductase
      activity, 32-33, 27 and 25 kDa protein subunits were commonly identified. These
      results suggest that oligomers of beta-crystallin and/or lambda-crystallin
      subunits may be associated with the DHA reductase activity. The present paper
      also discusses that the function of the reductase may be to enhance the
      antiphotoxidation capacity of the lens.

PMID- 11592300
TI  - Biological and clinical relevance of Laminin-5 in cancer.
AB  - The occurrence of metastases is the hallmark of cancer. Development of metastasis
      severely affects prognosis and survival. It limits or discourages therapeutic
      interventions since no therapies are available to block or prevent cancer
      invasion. In order to invade, epithelial cancer cells need to penetrate through
      the basement membrane (BM) and remove extra-cellular matrix (ECM) tissue
      boundaries. In this context, proteases play a key role since they can either
      degrade or process the ECM components and thereby support cancer cell invasion.
      Laminin-5 (Ln-5) is an ECM protein, expressed predominantly in the BM structure,
      that promotes static adhesion and hemidesmosome formation. However, it also
      stimulates cell migration and/or invasion after having been cleaved by matrix
      metalloproteinases (MMPs) such as MMP-2 and MT1-MMP. Based on its dual functions,
      it would be intriguing to elucidate the role that Ln-5 plays in cancer cell
      motility and metastasis. One possibility is that MMPs, secreted by cancer cells
      or by neighbouring stromal cells, can cleave the gamma2 chain of Ln-5 deposited
      along the advancing edge of tumors. Ln-5, and in particular its gamma2 chain, has
      been found to be preferentially expressed in the cytoplasm of epithelial human
      cancer cells located at the advancing edge of the tumor. Such a distribution,
      which is restricted only to malignancies, suggests that the gamma2 chain may be
      implicated in epithelial cancer growth and invasion. Although the clinical
      significance of this finding is not yet clear, it seems often to be associated
      with a more aggressive and invasive cancer phenotype. This article will review
      the current body of evidence implicating the Ln-5 molecule, and in particular its
      gamma2 chain, as an important player in the tumor cascade and progression to
      metastatic disease. This will then be followed by a discussion of the presented
      data and its limitations. Finally, suggestions will be provided to improve the
      current state of knowledge in the field and future implications will be briefly
      discussed.

PMID- 11592301
TI  - Antibodies to PAI-1 alter the invasive and migratory properties of human tumour
      cells in vitro.
AB  - Recent reports suggest that elevated levels of plasminogen activator inhibitor-1
      (PAI-1) may contribute to tumour progression. The studies reported here were
      designed to help elucidate PAI-1's contribution to the invasive and migratory
      phenotype. Antibodies to PA-1 dose-dependently, and significantly, inhibited the
      invasive and migratory potential of human HT1080 fibrosarcoma cells, as did an
      antibody to uPA and the plasmin inhibitor aprotinin. Invasion of the human
      melanoma cell line, BLM, was also attenuated by the anti-PAI-1 monoclonal
      antibody MAI-12. The non-invasive human melanoma cell line, IF6, which does not
      express uPA, provided further confirmation of PAI-1 and uPA's role as, upon
      transfection with uPA, this cell line attained an invasive phenotype, which was
      again attenuated by MAI-12. Although antibodies to PAI-1 did not affect the
      adhesion of HT1080 cells to vitronectin, the antibody to uPA reduced their
      attachment. Addition of exogenous PAI-1, however, prevented HT1080 cell adhesion
      (IC50 180 nM) and promoted cell detachment from vitronectin. Furthermore melanoma
      cells transfected with a uPA variant, which had an impaired interaction with PAI
      1, were not invasive and had impaired binding to vitronectin. These data
      highlight the importance of a balanced proteolysis and suggest an additional role
      for PAI-1 distinct from its role in proteolysis. These data also suggest that uPA
      and PAI-1 may co-operate in the migratory process by respectively facilitating
      the attachment to, and subsequent detachment from, vitronectin in the
      extracellular matrix. These results support the clinical findings and indicate
      that modulation of PAI-1 activity may be of therapeutic benefit for the treatment
      of cancer.

PMID- 11592302
TI  - Magnetic resonance imaging for the evaluation of a novel metastatic orthotopic
      model of human neuroblastoma in immunodeficient mice.
AB  - Neuroblastoma is the second most common solid tumor in children. So far few tumor
      models for this cancer have been reported in mice. We have created a murine tumor
      model for studying human neuroblastoma based on surgical orthotopic implantation
      in scid mice. Small fragments of subcutaneous tumors of SK-N-BE(2) human
      neuroblastoma cells expressing enhanced green fluorescent protein were surgically
      implanted near the left adrenal gland of scid mice. One hundred percent of the
      animals (n = 21) successfully implanted developed a large retroperitoneal tumor
      and became moribund between 22 and 57 days after implantation (mean survival time
      = 41 days). At the time of sacrifice the presence of bone marrow metastasis was
      detected by RT-PCR for green fluorescent protein in 95% of the cases. The growth
      of small tumor implants could be easily visualized and quantified by surveillance
      MR imaging, with a resolution of 117 x 117 x 750 microm in two orthogonal planes
      allowing accurate volume measurements, as well as assessment of necrosis and
      tissue invasion. This novel model should be a valuable tool to study the biology
      and therapeutic approaches to neuroblastoma.

PMID- 11592303
TI  - Immunolocalization of matrix metalloproteinases and their inhibitors in clinical
      specimens of bone metastasis from breast carcinoma.
AB  - Matrix metalloproteinases (MMPs) are essential in several stages of the
      metastatic process, and in normal bone development and remodeling. We explored
      whether the interaction between tumor cells and bone leads to changes in MMP and
      tissue inhibitor of MMP (TIMP) expression thus affecting osteolysis in metastatic
      bone disease. Using immunohistochemistry we have investigated the MMP/TIMP
      expression in tumor cells, fibroblasts, osteoblasts and osteoclasts. Thirty one
      specimens of bone metastasis from breast carcinoma were stained for MMP-1, -2, 
      9, MT1-MMP and TIMP-1, and -2 and compared with staining in normal breast tissue,
      primary breast carcinoma and normal bone. Specimens came from patients in three
      clinical scenarios: from open biopsies without or with pathological fracture, or
      bone marrow biopsies containing tumor from patients with pancytopenia but without
      clinical evidence of osteolysis. By bone histomorphometry the latter group showed
      a heavy tumor load not different from the open biopsy groups but displayed little
      active bone resorption and low numbers of osteoclasts. Cell type-specific
      MMP/TIMP expression was observed and the staining patterns were comparable
      between the three groups of patients. Though no major differences in the MMP/TIMP
      staining of tumor cells and fibroblasts were observed between bone metastasis and
      primary tumor, we showed that tumor cells do express MMPs capable of degrading
      bone matrix collagen. The number and activity of osteoclasts and osteoblasts was
      increased dramatically in bone metastases, their MMP/TIMP profiles, however, were
      not different from normal bone, suggesting that the mechanism of bone degradation
      by osteoclasts is not different from normal bone remodelling.

PMID- 11592304
TI  - The role of constitutive NF-kappaB activity in PC-3 human prostate cancer cell
      invasive behavior.
AB  - The purpose of this study was to determine if increased NF-kappaB activity of
      highly invasive PC-3 cells contributed to their invasive behavior. Increased NF
      kappaB activity has been observed in several malignant tumors and it may have an
      important role in tumorigenesis, progression and chemotherapy resistance. By
      serial selection, we obtained invasion variant PC-3 cell sublines. The PC-3 High
      Invasive cells invade readily through a Matrigel reconstituted basement membrane
      while PC-3 Low Invasive cells have low baseline invasion activity. In these
      studies, we discovered that NF-kappaB DNA binding activity was increased in PC-3
      High Invasive cells when compared to PC-3 Low Invasive cells by electrophoretic
      mobility shift assay (EMSA). Gel supershift assays showed a 4-fold increase in
      p65 containing complexes and a 2.2-fold increase in the p50 containing complexes
      in the PC-3 High Invasive cells. Luciferase reporter assays showed that NF-kappaB
      dependent transcription activity was increased 10.2 +/- 2.5-fold in the highly
      invasive cells (P < 0.002). The PC-3 High Invasive cells showed a constitutive
      increase in phospho-IkappaB alpha and introduction of the super-repressor IkappaB
      alpha S32/36A inhibited NF-kappaB activity to 19.2 +/- 2.5 percent of control
      transfected cells (P < or = 0.001). The IkappaBa super-repressor reduced the
      basement membrane invasion of PC-3 High Invasive cells from 6.2 +/- 1.1 to 3.8 +/
      0.4 percent (P < 0.002) with no decrease in cell viability or proliferation.
      These results demonstrate that increased NF-kappaB activity contributed directly
      to the invasive behavior of PC-3 High Invasive prostate cancer cells.

PMID- 11592305
TI  - Organ-specificity of the extravasation process: an ultrastructural study.
AB  - The process of extravasation of the high metastatic Lewis lung carcinoma line was
      examined in different organs. Four of the five organs (liver, lungs, brain and
      adrenals) represent the most frequent metastatic sites in humans. In the case of
      each organ 150-350 tumor cells were analysed. The interaction of tumor cells with
      endothelial cells and the basement membrane showed significant differences
      between the organs. In the liver and lungs, endothelial cells were found to
      migrate onto the surface of the tumor cells, resulting in the removal of tumor
      cells from the circulation. The process was initiated by development of
      cytoplasmic projections on the luminal surface of the endothelial cells. In the
      liver only half of the tumor cells showed basement membrane degradation even
      after 24 h, although 6 h after injection 40% of the tumor cells were sequestered
      from the circulation. In the adrenals and brain, tumor cells were not covered by
      endothelial cells instead, limited retraction of endothelial cells was followed
      by penetration of the basement membrane. In the kidney both types of tumor cell
      endothelial cell interactions were observed, but the process of extravasation was
      not completed, stopping as the tumor cells reached the basement membrane or the
      mesangial matrix. The time course of tumor cell extravasation also showed
      significant differences between the organs. The process was most rapid in case of
      the liver and adrenals. By 6 h 40-50% of the tumor cells were in the process of
      extravasation or were in an extracapillary position. These organs are
      preferential metastatic sites of this tumor line. The time of extravasation was
      much longer in the other organs (lungs 16 h, brain 48 h), for which this tumor
      line shows no preference. CONCLUSIONS: (1) Type and duration of tumor cell
      extravasation differ between the organs. (2) The time needed to reach
      extraluminal position, but not the type of extravasation correlates with the
      organ preference. (3) Endothelial cells of the lungs and liver can play a much
      more active role in the process of extravasation than previously suggested. (4)
      Tumor cells can complete the metastatic process without reaching a complete
      extracapillary position; contact with the basement membrane or extracellular
      matrix seems to be sufficient.

PMID- 11592307
TI  - Expression of angiogenesis-related genes in ovarian carcinoma--a
      clinicopathologic study.
AB  - Angiogenic factors play a role in tumor growth and spread. The object of this
      study was to analyze the correlation between mRNA expression of angiogenesis
      related genes and disease outcome in advanced-stage ovarian carcinomas. Sections
      from 66 primary ovarian carcinomas and metastatic lesions from 41 patients
      diagnosed with advanced stage ovarian carcinoma (FIGO stages III-IV) were
      evaluated for expression of basic fibroblast factor (bFGF), interleukin-8 (IL-8),
      and vascular endothelial growth factor (VEGF) using mRNA In Situ Hybridization
      (ISH). Patients were divided in two groups based on disease outcome. Long-term
      survivors (17 patients) and short-term survivors (24 patients) were defined using
      a double cut-off of 36 months for disease-free survival (DFS) and 60 months for
      overall survival (OS). Mean follow-up period was 70 months. The mean values for
      DFS and OS were 116 and 133 months for long-term survivors, as compared to 3 and
      21 months for short-term survivors, respectively. Expression of bFGF mRNA, most
      often intense, was detected in tumor and stromal cells in the majority of cases.
      Weak expression of IL-8 mRNA was detected in both cell compartments, while VEGF
      mRNA expression was limited to few cases. Primary tumors displayed higher bFGF
      and IL-8 mRNA expression. However, these differences did not reach statistical
      significance (P > 0.05). bFGF, IL-8 and VEGF mRNA expression in both tumor and
      stromal cells was comparable in tumors of long-term and short-term survivors, and
      showed no correlation with disease outcome in survival analysis (P > 0.05). bFGF
      is the major angiogenic factor expressed in ovarian carcinoma at the mRNA level.
      mRNA expression of VEGF, bFGF, and IL-8 does not appear to be a predictor of
      disease outcome in advanced-stage ovarian carcinoma.

PMID- 11592306
TI  - TGFbeta1 stimulates the secretion of matrix metalloproteinase 2 (MMP2) and the
      invasive behavior in human ovarian cancer cells, which is suppressed by MMP
      inhibitor BB3103.
AB  - The present study investigated the modulatory role of transforming growth factor
      beta 1 (TGFbeta1) on the secretion of matrix metalloproteinases (MMPs) and tested
      whether the altered secretion of MMPs could directly affect the invasive behavior
      of ovarian cancer cells. To this aim, human ovarian cancer SKOV3 cells were
      treated once with vehicle or various concentrations of TGFbeta1 for 24 h.
      Gelatinase activities in conditioned media were analyzed by zymography and
      densitometry. TGFbeta1 dose-dependently stimulated the secretion of a 68-kDa
      gelatinase, which was characterized as an MMP because its activity was inhibited
      by a metalloproteinase inhibitor 1,10-phenanthroline, and by a synthetic MMP
      inhibitor BB3103. In addition, we used aminophenylmercuric acetate (APMA) to
      activate latent gelatinases. APMA time-dependently decreased the activity of 68
      kDa gelatinase, and increased the activities of 64- and 62-kDa gelatinolytic
      bands. The 68-kDa gelatinase was further characterized as MMP2 (gelatinase A) by
      immunoblotting analysis. We then tested TGFbeta1 effect on the invasive potential
      of SKOV3 cells as assessed by the migration ability through reconstituted
      basement membrane, and further investigated whether TGFbeta1 may act through
      modulating the MMP activity to affect ovarian cancer cell invasion. The results
      show that TGFbeta1 stimulated the invasive behavior of SKOV3 cells, and that MMP
      inhibitor BB3103 abrogated this effect of TGFbeta1. In conclusion, this study
      indicates that TGFbeta1 may act partly through stimulating the secretion of MMP
      in promoting the invasive behavior of human ovarian cancer cells. Furthermore,
      this work supports the idea that specific MMP inhibitors of the hydroxamate class
      could be therapeutically useful in controlling cancer cell invasion/metastasis.

PMID- 11592308
TI  - Partial purification of a liver-derived tumor cell growth inhibitor that
      differentially inhibits poorly-liver metastasizing cell lines: identification as
      an active subunit of arginase.
AB  - Organ specific tumor metastasis is thought in part to require the ability of
      metastatic cells to respond to target-organ-associated growth factors or to avoid
      the effects of target organ associated growth inhibitors. We previously found
      that murine and rat liver-conditioned media inhibited the growth of the poorly
      liver metastasizing murine RAW117-P large-cell lymphoma cells more than their
      highly liver-metastasizing RAW117-H10 counterparts. Using a six step
      chromatographic procedure, the major RAW117-P cell proliferation inhibitor from a
      rat liver extract was purified. The factor displayed a Mr of approximately 35,000
      and an isoelectric point > 8.5. This material inhibited the growth of many cells
      at high concentration; however, in dose-response studies it displayed a higher
      IC50 for highly-liver metastatic murine RAW117-H10 lymphoma and human KM12SM
      colon carcinoma cells than for their poorly-liver metastatic counterparts.
      Attempts to identify the growth inhibitor led to the supplementation of tissue
      culture inhibitor assays with various components, including excess amino acids,
      and this was found to completely abrogate the factor's activity. Specifically,
      the addition of excess arginine resulted in the complete cellular recovery from
      inhibitor exposure. This tentatively identified the liver growth inhibitor as the
      enzyme arginase, a Mr approximately 10,000 multisubunit protein. A microtiter
      plate-based assay for arginase was developed and the purification repeated using
      human liver as a source of activity and the human KM12C colon carcinoma line as a
      target. The growth inhibitory and arginase activities were found to co-purify,
      identifying the factor as arginase. Highly-metastatic cells displayed no ability
      to preferentially inactivate or inhibit the activity of arginase, but they did
      they display slightly greater amounts of intracellular arginine. The liver is a
      major site of arginase localization as the enzyme is required for the functioning
      of the urea cycle. The results indicate that certain liver-colonizing tumor cells
      can escape, to a degree, the proliferation-damping effects of arginine depletion.

PMID- 11592311
TI  - FDA exploring safety aspects of cloned animals.

PMID- 11592309
TI  - The relationship of BRMS1 and RhoGDI2 gene expression to metastatic potential in
      lineage related human bladder cancer cell lines.
AB  - We have recently characterized a human bladder cancer cell line T24 and a more
      aggressive lineage related variant of it, T24T. To gain further insights, we have
      studied their metastatic ability in an in vivo model system. Results show that
      T24 forms significantly fewer [4/12 (1/11) mice had metastases with 1-2
      lesions/mouse] metastasis in SCID/bg mice than T24T [14/14 (6/6) mice had
      metastases with a mean of 24-28 lesions/mouse]. To begin exploring the mechanisms
      underlying this difference, we evaluated the mRNA and protein expression levels
      of metastasis-suppressor genes, known to be important in the progression of other
      cancers, in our model of bladder cancer progression. A higher mRNA expression of
      BRMS1, a metastasis suppressor in breast cancer, was observed in T24 cells. In
      addition, RhoGDI2 mRNA expression was only observed in T24 when compared to T24T,
      suggesting that Rho activation might play a significant role in the metastatic
      cascade. However, a basal level mRNA expression of KISS1, described as metastasis
      suppressor in melanoma and breast, was observed in both the lines and had
      slightly higher expression in T24T. No difference of Nm23-H1, KAI1, MKK4/SEK1 and
      E-Cadherin protein levels were noted between these two lines. In summary, it
      appears that the T24/T24T paired cell lines constitute a useful model for the
      study of human bladder cancer metastasis that will allow both the discovery and
      mechanistic evaluation of genes potentially involved in this process.

PMID- 11592312
TI  - Researchers home in on leishmaniasis vaccine.

PMID- 11592310
TI  - Platelet-endothelial cell adhesion molecule-1 (CD31) redistributes from the
      endothelial junction and is not required for the transendothelial migration of
      melanoma cells.
AB  - We have examined the role of platelet-endothelial cell adhesion molecule-1 (PECAM
      1/CD31) during the transendothelial migration of melanoma cells using a novel in
      vitro system. Comparable studies have suggested the involvement of PECAM-1 in
      leukocyte transendothelial migration. Such studies have been confirmed using in
      vivo models of inflammation. These studies prompted us to examine the role of
      PECAM-1 in tumor cell transendothelial migration. Anti-PECAM-1 monoclonal
      antibodies, known to block leukocyte transendothelial migration, were tested in
      co-cultures of human melanoma cells seeded on a monolayer of human lung
      microvascular endothelial cells. None of these antibodies inhibited the
      transmigration of melanoma cells. Moreover, confocal microscopy revealed the
      dissolution of the PECAM-1 adhesion complexes in the endothelial junctions
      associated with melanoma cells and the lack of PECAM-1 in heterotypic contacts
      between transmigrating melanoma cells and adjacent endothelial cells. These data,
      therefore, indicate that PECAM-1 is not required for the transendothelial
      migration of melanoma cells.

PMID- 11592313
TI  - Involvement of microbial respiratory pathogens in acute interstitial pneumonia in
      feedlot cattle.
AB  - OBJECTIVE: To evaluate viral and bacterial respiratory pathogens and Mycoplasma
      spp isolated from lung tissues of cattle with acute interstitial pneumonia (AIP)
      and cattle that had died as a result of other causes. SAMPLE POPULATION: 186
      samples of lung tissues collected from cattle housed in 14 feedlots in the
      western United States. PROCEDURE: Lung tissues were collected during routine
      postmortem examination and submitted for histologic, microbiologic, and
      toxicologic examinations. Histologic diagnoses were categorized for AIP,
      bronchopneumonia (BP), control samples (no evidence of disease), and other
      disorders. RESULTS: Cattle affected with AIP had been in feedlots for a mean of
      1272 days before death, which was longer than cattle with BP and control cattle.
      Detection of a viral respiratory pathogen (eg, bovine respiratory syncytial virus
      [BRSV], bovine viral diarrhea virus, bovine herpesvirus 1, or parainfluenza virus
      3) was not associated with histologic category of lung tissues. Bovine
      respiratory syncytial virus was detected in 8.3% of AIP samples and 24.0% of
      control samples. Histologic category was associated with isolation of an aerobic
      bacterial agent and Mycoplasma spp. Cattle with BP were at greatest risk for
      isolation of an aerobic bacterial agent and Mycoplasma spp. CONCLUSIONS AND
      CLINICAL RELEVANCE: Analysis of these results suggests that AIP in feedlot cattle
      is not a consequence of infection with BRSV. The increased, risk of isolation of
      an aerobic bacterial agent from cattle with AIP, compared with control cattle,
      may indicate a causal role or an opportunistic infection that follows development
      of AIP.

PMID- 11592314
TI  - Association of 3-methyleneindolenine, a toxic metabolite of 3-methylindole, with
      acute interstitial pneumonia in feedlot cattle.
AB  - OBJECTIVE: To compare concentrations of 3-methyleneindolenine (3MEIN) in lung
      tissues obtained from feedlot cattle that died as a result of acute interstitial
      pneumonia (AIP) and cattle that died as a result of other causes and to compare
      blood concentrations of 3MEIN in healthy feedlot cattle and feedlot cattle with
      AIP. STUDY POPULATION: Blood samples and lung tissues collected from 186 cattle
      housed in 14 feedlots in the western United States. PROCEDURE: Samples of lung
      tissues were collected during routine postmortem examination and submitted for
      histologic, microbiologic, and toxicologic examination. Blood samples were
      collected from cattle with clinical manifestations of AIP and healthy penmates.
      Histologic diagnoses were categorized as AIP, bronchopneumonia (BP), control
      samples, and other disorders. Concentrations of 3MEIN were determined in lung
      tissues and blood samples, using an ELISA. RESULTS: Concentrations of 3MEIN in
      lung tissues were significantly greater in AIP and BP samples, compared with
      control samples. Absorbance per microgram of protein did not differ between BP
      and AIP samples. Blood concentrations of 3MEIN were significantly greater in
      cattle with AIP, compared with healthy cattle or cattle with BP. Odds of an
      animal with AIP being a heifer was 3.1 times greater than the odds of that animal
      being a steer. CONCLUSIONS AND CLINICAL RELEVANCE: Increased pulmonary production
      of 3MEIN may be an important etiologic factor in feedlot-associated AIP.

PMID- 11592315
TI  - Effect of orally administered cimetidine and ranitidine on abomasal luminal pH in
      clinically normal milk-fed calves.
AB  - OBJECTIVE: To characterize the change of pH in the abomasal lumen throughout a 24
      hour period, to determine whether pH of the abomasal body differs from pH of the
      pyloric antrum, and to determine whether oral administration of cimetidine and
      ranitidine alters pH of the abomasal lumen in milk-fed calves. ANIMALS: 5 male
      dairy calves (4 Holsteins-Friesian, 1 Ayrshire), 5 to 15 days old. PROCEDURE:
      Cannulas were surgically positioned in the abomasal body and pyloric antrum of
      each calf. Calves received the following treatments in a randomized crossover
      design: milk replacer (60 ml/kg of body weight, q 12 h [untreated control
      calves]), milk replacer and cimetidine (50 or 100 mg/kg, q 8 h), or milk replacer
      and ranitidine (10 or 50 mg/kg, q 8 h). The pH of the abomasal body and pyloric
      antrum was measured for 24 hours, using miniature glass pH electrodes. RESULTS:
      Suckling of milk replacer immediately increased abomasal luminal pH from 1.4 to
      6.0, followed by a gradual decrease to preprandial values by 6 hours. Preprandial
      and postprandial pH values were not significantly different between the abomasal
      body and pyloric antrum, indicating lack of pH compartmentalization in the
      abomasum of milk-fed calves. Administration of cimetidine and ranitidine caused a
      significant dose-dependent increase in mean 24-hour abomasal luminal pH.
      CONCLUSIONS AND CLINICAL RELEVANCE: Abomasal acid secretion in milk-fed calves is
      mediated in part by histamine type-2 receptors. Cimetidine and ranitidine may be
      efficacious in the treatment of abomasal ulcers in milk-fed calves.

PMID- 11592316
TI  - Telomere length and telomerase activity in canine mammary gland tumors.
AB  - OBJECTIVE: To measure telomere length and telomerase activity in naturally
      occurring canine mammary gland tumors. SAMPLE POPULATION: 27 mammary gland tumor
      specimens obtained during resection or necropsy and 12 mammary gland tissue
      specimens obtained from healthy (control) dogs. PROCEDURE: Telomere length in
      tissue specimens was measured by use of restriction endonuclease digestion and
      Southern blot analysis. Telomerase activity was measured by use of a telomeric
      repeat amplification protocol assay. RESULTS: Telomere length in mammary gland
      tumors ranged from 11.0 to 21.6 kilobase pairs (kbp; mean +/- SEM, 14.5+/-0.5
      kbp) but did not differ among tumor types. Telomeres in mammary gland tumors were
      slightly shorter than in normal tissue specimens, but telomere length could not
      be directly compared between groups, because mean age of dogs was significantly
      different between groups. Age was negatively correlated with telomere length in
      control dogs but was not significantly correlated with length in affected dogs.
      Telomerase activity was detected in 26 of 27 mammary gland tumors and in 4 of 12
      normal tissue specimens. However, telomerase activity and telomere length were
      not correlated in tumor specimens. CONCLUSIONS AND CLINICAL RELEVANCE: Telomere
      length is maintained in canine mammary gland tumors regardless of the age of the
      affected dog. Measurement of telomere length may be a useful tool for monitoring
      the in vivo effects of telomerase inhibitors in dogs with tumors.

PMID- 11592317
TI  - Effects of exogenous insulin on glucose tolerance in alpacas.
AB  - OBJECTIVE: To evaluate the effects of exogenous insulin on clearance of exogenous
      glucose in alpacas. ANIMALS: 7 adult castrated male alpacas. PROCEDURE: Prior to
      each of 2 trials, food was withheld for 8 hours. Glucose (0.5 g/kg of body
      weight) was then administered by rapid IV infusion. During 1 of the trials,
      regular insulin (0.2 U/kg, IV) was also administered 15 minutes later. Blood was
      collected immediately before (0 minutes) and 15, 20, 25, 30, 45, 60, 90, 120,
      180, and 240 minutes after glucose administration. Plasma concentrations of
      glucose and lactate were determined, and glucose fractional turnover rate and
      plasma half-life were calculated. RESULTS: Insulin treatment caused a significant
      increase in fractional turnover rate of glucose and plasma lactate concentration.
      Plasma glucose concentrations were less in insulin-treated alpacas from 30
      minutes after glucose administration (15 minutes after insulin administration)
      until the conclusion of each trial, compared with nontreated alpacas. In
      addition, plasma glucose concentration in insulin-treated alpacas returned to
      baseline values 1 hour sooner than in the nontreated group. CONCLUSIONS AND
      CLINICAL RELEVANCE: Glucose uptake in alpacas improves after insulin treatment,
      suggesting that administration of exogenous insulin will increase the therapeutic
      and decrease the pathologic effects of exogenous glucose administered to
      hypoglycemic alpacas. However, alpacas and other New World camelids should be
      monitored carefully during treatment with glucose or insulin, because these
      species appear to be partially insulin resistant.

PMID- 11592318
TI  - In vitro experimental study of the effect of radial shortening and ulnar
      ostectomy on contact patterns in the elbow joint of dogs.
AB  - OBJECTIVE: To determine effects of incremental radial shortening and subsequent
      ulnar ostectomies on joint surface contact patterns in a canine elbow joint
      model. SAMPLE POPULATION: Paired forelimbs from 9 adult dogs. PROCEDURE: Joint
      casting was performed by placement of colored polymethylmethacrylate in the elbow
      joint cavity and loading in a materials testing system at physiologic angle and
      load. Joint casting was performed in unaltered specimens, after radial
      shortening, and after subsequent distal ulnar ostectomy, proximal ulnar
      ostectomy, and proximal ulnar ostectomy with intramedullary pinning. Computer
      aided analysis of photographs of proximal radial and ulnar articular surfaces
      without joint casts was performed before and after each casting procedure.
      RESULTS: All increments of radial shortening changed the size and location of
      radial and ulnar contact areas. The radial contact area became smaller, the
      anconeal contact area disappeared, the medial coronoid contact area migrated
      craniolaterally, and the lateral projection of the coronoid process became a
      contact area. A proximal ulnar ostectomy stabilized with an intramedullary pin
      restored normal contact area size and location and restored continuity of the
      radial and coronoid contact areas across the radioulnar articulation in 6 of 10
      specimens. A midshaft ulnar ostectomy, distal to the level of the radioulnar
      ligament, had no effect on contact patterns. A proximal ulnar ostectomy without
      stabilization resulted in varus deformity during loading. CONCLUSIONS AND
      CLINICAL RELEVANCE: Proximal radial shortening, which creates articular step
      incongruity, changes the location and size of the radioulnar contact areas.
      Dynamically stabilized ulnar ostectomies proximal to the radioulnar ligament
      restore contact patterns in vitro.

PMID- 11592319
TI  - Effects of beta-aminopropionitrile on equine tendon metabolism in vitro and on
      effects of insulin-like growth factor-I on matrix production by equine tenocytes.
AB  - OBJECTIVE: To investigate effects of beta-aminopropionitrile and a combination of
      insulin-like growth factor (IGF)-I and beta-aminopropionitrile on metabolism of
      equine tendon fibroblasts. SAMPLE POPULATION: Flexor tendon explants from 3
      horses. PROCEDURE: Explants received 1 of 4 treatments (control, IGF-I, beta
      aminopropionitrile, and IGF-I/beta-aminopropionitrile) for 10 days, and message
      expression for collagen types I and III was assessed by use of in situ
      hybridization. Histologic findings, new protein production, and quantitative
      determinations of glycosaminoglycan, DNA, and de novo collagen synthesis were
      made. RESULTS: Insulin-like growth factor-I stimulated an anabolic response in
      tendon. Collagen synthesis and glycosaminoglycan and DNA content of explants were
      all increased. Beta-aminopropionitrile significantly suppressed collagen
      synthesis, which was not ameliorated by concurrent IGF-I treatment. Beta
      aminopropionitrile caused alterations in cell morphology characterized by large
      round cells with eccentric nuclei and decreased density of collagen fibers.
      Protein production and collagen type-III mRNA expression were reduced in these
      cells. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with beta-aminopropionitrile
      resulted in decreased production of protein and collagen synthesis, which could
      be expected to suppress tendon healing. The negative effects of beta
      aminopropionitrile could not be abrogated by addition of IGF-I to the medium.
      Treatment resulted in alterations in cell morphology and matrix consistency,
      which could further delay tendon healing. Beta-aminopropionitrile may impair
      tendon healing at a cellular level by decreasing collagen production or
      increasing rate of degradation of existing matrix. Because of reduced
      crosslinking during beta-aminopropionitrile treatment, in combination with
      transiently decreased tensile strength, alterations in collagen content and
      structure may weaken the healing tendon.

PMID- 11592320
TI  - Effects of exercise on the diameter of collagen fibrils in the central core and
      periphery of the superficial digital flexor tendon in foals.
AB  - OBJECTIVE: To determine the effects of exercise on collagen fibril diameter
      distribution in the superficial digital flexor tendon (SDFT) of foals. ANIMALS:
      43 Dutch Warmblood foals. PROCEDURE: From 1 week until 5 months of age, group-1
      foals (n = 14) were housed in stalls and not exercised, group-2 foals (14) were
      housed in stalls but were exercised, and group-3 foals (15) were maintained at
      pasture. Biopsy specimens were collected from the SDFT at 2 months, and 8 foals
      in each group were euthanatized at 5 months. Remaining foals were housed together
      in a loose stall and paddock until euthanatized at 11 months. After euthanasia,
      specimens were collected from the SDFT; all specimens were analyzed by use of
      electron microscopy. Collagen fibrillar index (CFI), mass average diameter
      (MAvD), and area dependent diameter (ADD) were compared among groups. RESULTS:
      Exercise-related differences in fibril distribution were not detected among
      groups at 2 months. At 5 months, ADD in peripheral specimens was significantly
      greater in group 1 than group 3. At 11 months, MAvD in core specimens was
      significantly less in group 3, compared with the other groups. However, in
      peripheral specimens, MAvD was significantly less in groups 2 and 3. CONCLUSIONS
      AND CLINICAL RELEVANCE: Collagen fibril restructuring in the SDFT of foals is in
      part an exercise-driven process. Withholding exercise may cause a delay in fibril
      development that can be partially overcome by increasing exercise at a later age.
      Exercise type may also affect remodeling of the SDFT in foals.

PMID- 11592321
TI  - Development and evaluation of a highly sensitive and specific blocking enzyme
      linked immunosorbent assay and polymerase chain reaction assay for diagnosis of
      bovine leukemia virus infection in cattle.
AB  - OBJECTIVE: To develop a blocking ELISA for detection of bovine leukemia virus
      (BLV) antibodies that is comparable to a radioimmunoprecipitation (RIP) assay, to
      evaluate use of this ELISA for identification of BLV-infected herds, and to
      develop a polymerase chain reaction (PCR) assay for direct diagnosis of infection
      with BLV. SAMPLE POPULATION: Serum samples and pooled bulk-tank milk samples from
      cattle. PROCEDURE: The blocking ELISA was developed, using BLV gp51 as antigen,
      captured by a selected bovine polyclonal serum. A nested PCR was conducted with
      primers specific for a segment of the pol region of the BLV genome. RESULTS:
      Sensitivity and specificity of the ELISA were comparable to those of the RIP
      assay. Use of the ELISA on pooled milk samples allowed identification of herds in
      which prevalence of BLV infection among lactating cows was as low as 2.5%. Pooled
      milk samples from BLV-free herds did not react in the ELISA. All cattle that had
      positive results for the nested PCR had BLV antibodies, but cattle with
      consistantly low antibody titers required examination of sequential DNA samples
      to detect viral sequences. None of the 63 antibody-negative cattle had positive
      results for the PCR. CONCLUSIONS AND CLINICAL RELEVANCE: This ELISA is a highly
      specific and sensitive assay for the detection of BLV antibodies in serum and
      milk samples of cattle. Examination of pooled milk samples with the ELISA
      provides a reliable, practical, and economic procedure for identification of BLV
      infected herds. The nested PCR also constitutes a specific procedure for direct
      diagnosis of infection with BLV.

PMID- 11592322
TI  - Telomerase activity as a marker for malignancy in feline tissues.
AB  - OBJECTIVE: To establish the diagnostic significance of the telomeric repeat
      amplification protocol (TRAP) assay in detecting feline malignancies. SAMPLE
      POPULATION: Solid tissue specimens collected from 33 client-owned cats undergoing
      diagnostic or therapeutic procedures at the University of Illinois Veterinary
      Medical Teaching Hospital between July 1997 and September 1999 and an additional
      20 tissue samples were collected from 3 clinically normal control cats
      euthanatized at the conclusion of an unrelated study. PROCEDURE: The TRAP assay
      was used for detection of telomerase activity. Each result was compared to its
      respective histopathologic diagnosis. RESULTS: Twenty-nine of 31 malignant and 1
      of 22 benign or normal tissue samples had telomerase activity, indicating 94%
      sensitivity and 95% specificity of the TRAP assay in our laboratory. CONCLUSIONS
      AND CLINICAL RELEVANCE: The diagnostic significance of telomerase activity has
      been demonstrated in humans and recently in dogs by our laboratory. We tested
      feline samples to determine whether similar patterns of telomerase activity
      exist. On the basis of our results, the TRAP assay may be clinically useful in
      providing a rapid diagnosis of malignancy in cats. The telomerase enzyme may also
      serve as a therapeutic target in feline tumors.

PMID- 11592323
TI  - Use of sample size for estimating efficacy of a vaccine against an infectious
      disease.
AB  - OBJECTIVE: To determine the sample size necessary to evaluate the efficacy of a
      vaccine in a population. PROCEDURE: An equation was coded into a computer
      spreadsheet to compare the traditional sample size calculation with that needed
      when evaluating the efficacy of a vaccine applied in a population. RESULTS: The
      traditional approach used to conservatively estimate sample size necessary to
      detect a given difference in group proportions potentially greatly underestimates
      the number of animals needed for vaccine efficacy (VE) trials. In VE trials, it
      is necessary to estimate the effect of population-level vaccination prior to
      estimating sample size. In VE trials, as incidence proportion in the population
      or herd decreases or VE decreases, necessary sample size increases. CONCLUSIONS
      AND CLINICAL RELEVANCE: In designing a clinical or field trial, such as one to
      evaluate the efficacy of a vaccine against an infectious disease in a population,
      one needs to approach sample size calculations in a nontraditional manner. The
      proportion of the population vaccinated, disease transmission dynamics, and VE
      will affect the incidence in the nonvaccinated and vaccinated groups and, hence,
      sample size. Thus, estimation of the effect of the vaccination on the population
      must be made prior to calculating sample size. Otherwise, sample size and the
      power to identify VE will be insufficient.

PMID- 11592324
TI  - Model formulation and determination of in vitro parameters of a noninvasive
      method to calculate flexor tendon forces in the equine forelimb.
AB  - OBJECTIVE: To describe a method to calculate flexor tendon forces on the basis of
      inverse dynamic analysis and an in vitro model of the equine forelimb and to
      quantify parameters for the model. SAMPLE POPULATION: 38 forelimbs of 23 horses
      that each had an estimated body mass of > or = 500 kg. PROCEDURE: Longitudinal
      limb sections were used to determine the lines of action of the tendons.
      Additionally, limb and tendon loading experiments were performed to determine
      mechanical properties of the flexor tendons. RESULTS: The study quantified the
      parameters for a pulley model to describe the lines of action. Furthermore,
      relationships between force and strain of the flexor tendons and between fetlock
      joint angle and suspensory ligament strain were determined, and the ultimate
      strength of the tendons was measured. CONCLUSION AND CLINICAL RELEVANCE: The
      model enables noninvasive determination of forces in the suspensory ligament,
      superficial digital flexor tendon, and distal part of the deep digital flexor
      (DDF) tendon. In addition, it provides a noninvasive measure of loading of the
      accessory ligament of the DDF tendon for within-subject comparisons. However,
      before application, the method should be validated. The model could become an
      important tool for use in research of the cause, prevention, and treatment of
      tendon injuries in horses.

PMID- 11592325
TI  - Sensitivity analysis and application to trotting of a noninvasive method to
      calculate flexor tendon forces in the equine forelimb.
AB  - OBJECTIVE: To test the sensitivity to measurement and modeling errors of a method
      for noninvasive calculation of flexor tendon forces in the equine forelimb and to
      calculate tendon forces for Dutch Warmblood horses during trotting. SAMPLE
      POPULATION: A normative set of kinematic and ground-reaction force (GRF) data
      obtained from horses during trotting in another study. PROCEDURE: Forces in the
      flexor tendons were calculated from the data set before and after addition of
      fixed relative and absolute errors. Amount of error was based on normal accuracy
      of the variables. A similar analysis was performed for a measure of strain of the
      accessory ligament of the deep digital flexor tendon. RESULTS: The only errors
      that had a substantial influence on accuracy were modeling errors in the
      mechanical properties of the suspensory ligament and measurement errors in the
      point of application of the GRF and position of the marker on the distal
      interphalangeal joint. Influence of the measurement errors could be minimized by
      applying usual correction methods. CONCLUSIONS AND CLINICAL RELEVANCE: After
      correction of measurement errors, the method can be used to calculate mean tendon
      forces for a group of horses and to evaluate the influence of factors such as
      surface properties, type of shoe, speed, and fatigue on tendon forces. The method
      could become an important tool for use in research on the cause, prevention, and
      treatment of tendon injuries in horses.

PMID- 11592326
TI  - Spatial distribution of seropositivity to the causative agent of granulocytic
      ehrlichiosis in dogs in California.
AB  - OBJECTIVE: To assess spatial and temporal patterns of seroprevalence among dogs
      in California to the causative agent of granulocytic ehrlichiosis (GE). SAMPLE
      POPULATION: Sera of 1,082 clinically normal dogs from 54 of 59 counties in
      California in 1997 to 1998. PROCEDURES: Serum-specific IgG reactivity to
      Ehrlichia equi was assessed by use of an immunofluorescent antibody assay, using
      E. equi-infected horse neutrophils as substrate. Data were analyzed, using a
      geographic information system. Spatial analysis of seroprevalence included first
      order Bayesian analysis of seroprevalence and second order analysis of clustering
      by K-function and Cuzick-Edwards tests. Monthly seroprevalence among dogs was
      examined by use of regression on monthly densities of Ixodes pacificus adults and
      nymphs. RESULTS: Seroprevalence among dogs to E. equi was 8.68%. Data were
      seasonally bimodal with highest prevalence in winter (when adult ticks were
      abundant) and a secondary peak in late spring (corresponding to nymphal ticks).
      Humboldt County had the highest seroprevalence (47.3%), and other northern coast
      range counties had seroprevalence from 15 to 30%. CONCLUSIONS AND CLINICAL
      RELEVANCE: The patchy distribution of exposure to Ehrlichia organisms is a subset
      of the distribution of the tick vector. This may reflect enzootic cycles or
      climatic or historical factors that limited the range of the disease. Dogs,
      horses, and humans from north coast range counties in California are at increased
      risk of GE. These data provide a background for assessing risk of infection in
      horses and dogs, depending on geographic location. Dogs may be sentinels for
      assessing risk of GE in humans.

PMID- 11592327
TI  - Pharmacokinetics of fluconazole following intravenous and oral administration and
      body fluid concentrations of fluconazole following repeated oral dosing in
      horses.
AB  - OBJECTIVE: To determine the pharmacokinetics of fluconazole in horses. ANIMALS: 6
      clinically normal adult horses. PROCEDURE: Fluconazole (10 mg/kg of body weight)
      was administered intravenously or orally with 2 weeks between treatments. Plasma
      fluconazole concentrations were determined prior to and 10, 20, 30, 40, and 60
      minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after
      administration. A long-term oral dosing regimen was designed in which all horses
      received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24
      hours for 10 days. Fluconazole concentrations were determined in aqueous humor,
      plasma, CSF, synovial fluid, and urine after administration of the final dose.
      RESULTS: Mean (+/- SD) apparent volume of distribution of fluconazole at steady
      state was 1.21+/-0.01 L/kg. Systemic availability and time to maximum plasma
      concentration following oral administration were 101.24+/-27.50% and 1.97+/-1.68
      hours, respectively. Maximum plasma concentrations and terminal half-lives after
      IV and oral administration were similar. Plasma, CSF, synovial fluid, aqueous
      humor, and urine concentrations of fluconazole after long-term oral
      administration of fluconazole were 30.50+/-23.88, 14.99+/-1.86, 14.19+/-5.07,
      11.39+/-2.83, and 56.99+/-32.87 microg/ml, respectively. CONCLUSIONS AND CLINICAL
      RELEVANCE: Bioavailability of fluconazole was high after oral administration to
      horses. Long-term oral administration maintained plasma and body fluid
      concentrations of fluconazole above the mean inhibitory concentration (8.0 mg/ml)
      reported for fungal pathogens in horses. Fluconazole may be an appropriate agent
      for treatment of fungal infections in horses.

PMID- 11592328
TI  - Number of Cryptosporidium parvum oocysts or Giardia spp cysts shed by dairy
      calves after natural infection.
AB  - OBJECTIVE: To determine the total number of Cryptosporidium parvum oocysts and
      Giardia spp cysts shed by dairy calves during the period when they are most at
      risk after natural infection. ANIMALS: 478 calves naturally infected with C.
      parvum and 1,016 calves naturally infected with Giardia spp. PROCEDURE: Oocysts
      or cysts were enumerated from fecal specimens. Distribution of number of oocysts
      or cysts versus age was used to determine the best fitting mathematic function.
      Number of oocysts or cysts per gram of feces for a given duration of shedding was
      computed by determining the area under the curve. Total number of oocysts or
      cysts was calculated by taking the product of the resultant and the expected mass
      of feces. RESULTS: Intensity of Cparvum oocyst shedding was best described by a
      second-order polynomial function. Shedding increased from 4 days of age, peaked
      at day 12, and then decreased. An infected 6-day-old calf would produce 3.89 x
      10(10) oocysts until 12 days old. Pattern of shedding of Giardia spp cysts was
      best described by exponential functions. Intensity of shedding increased from 4
      days of age, peaked at day 14, and then decreased. An infected calf would produce
      3.8 x 10(7) cysts from day 50 until day 56. CONCLUSIONS AND CLINICAL RELEVANCE:
      The large number of oocysts and cysts shed indicates that shedding by dairy
      cattle poses a risk for susceptible calves and people. Estimates reported here
      may be useful to aid in designing cost-effective strategies to manage this risk.

PMID- 11592329
TI  - Effects of dietary fat and L-carnitine on plasma and whole blood taurine
      concentrations and cardiac function in healthy dogs fed protein-restricted diets.
AB  - OBJECTIVE: To evaluate plasma taurine concentrations (PTC), whole blood taurine
      concentrations (WBTC), and echocardiographic findings in dogs fed 1 of 3 protein
      restricted diets that varied in fat and L-carnitine content. ANIMALS: 17 healthy
      Beagles. DESIGN: Baseline PTC and WBTC were determined, and echocardiography was
      performed in all dogs consuming a maintenance diet. Dogs were then fed 1 of 3
      protein-restricted diets for 48 months: a low-fat (LF) diet, a high-fat and L
      carnitine supplemented (HF + C) diet, or a high-fat (HF) diet. All diets
      contained methionine and cystine concentrations at or above recommended
      Association of American Feed Control Officials (AAFCO) minimum requirements.
      Echocardiographic findings, PTC, and WBTC were evaluated every 6 months. RESULTS:
      The PTC and WBTC were not significantly different among the 3 groups after 12
      months. All groups had significant decreases in WBTC from baseline
      concentrations, and the HF group also had a significant decrease in PTC. One dog
      with PT and WBT deficiency developed dilated cardiomyopathy (DCM). Taurine
      supplementation resulted in significant improvement in cardiac function. Another
      dog with decreased WBTC developed changes compatible with early DCM. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results revealed that dogs fed protein-restricted diets
      can develop decreased taurine concentrations; therefore, protein-restricted diets
      should be supplemented with taurine. Dietary methionine and cystine
      concentrations at or above AAFCO recommended minimum requirements did not prevent
      decreased taurine concentrations. The possibility exists that AAFCO recommended
      minimum requirements are not adequate for dogs consuming protein-restricted
      diets. Our results also revealed that, similar to cats, dogs can develop DCM
      secondary to taurine deficiency, and taurine supplementation can result in
      substantial improvement in cardiac function.

PMID- 11592330
TI  - Development of a functional scoring system in dogs with acute spinal cord
      injuries.
AB  - OBJECTIVES: To develop and compare the reliability of 2 methods of scoring pelvic
      limb gait in dogs recovering from thoracolumbar spinal cord injuries and to use
      this scoring system to determine the rate and level of functional recovery of
      dogs with acute thoracolumbar intervertebral disk herniations. ANIMALS: 46 dogs
      with spinal cord injuries resulting from intervertebral disk herniations.
      PROCEDURE: Dogs' gaits were videotaped at different time intervals after injury.
      In phase 1 of the study, the stages of recovery of pelvic limb function were
      identified, and a numeric scoring system was devised to reflect that recovery. In
      phase 2, pelvic limb gait was scored by different observers, using a numeric and
      a visual analog scale. Intra- and interobserver coefficients of variability of
      both methods were compared. In phase 3, pelvic limb function was scored, using
      the numeric scale at various intervals after acute thoracolumbar disk
      herniations. RESULTS: The numeric scale was significantly more reliable than the
      visual analog scale when both intra- and interobserver coefficients of
      variability were evaluated. Dogs that were paraplegic with no deep pain sensation
      recovered at different rates during the first 3 months, whereas dogs that were
      paraplegic with deep pain sensation typically recovered within 1 month of injury.
      CONCLUSIONS: Pelvic limb gait of dogs recovering from thoracolumbar spinal cord
      injuries can be reliably quantified, using a numeric scale. This scale will
      facilitate the performance of clinical trials aimed at improving the outcome of
      acute spinal cord injuries.

PMID- 11592331
TI  - Effects of intra-articular injections of bufexamac suspension in healthy horses.
AB  - OBJECTIVE: To evaluate the effects of intra-articular (IA) injections of
      bufexamac in horses, focusing particularly on the effects of bufexamac on
      articular cartilage. ANIMALS: 20 Standardbreds. PROCEDURE: Horses were randomly
      allocated into 4 groups consisting of 5 horses each, and 20, 60, or 100 mg of
      bufexamac or 1 ml of sterile saline (0.9% NaCl) solution (control) was injected
      into 1 intercarpal joint at weekly intervals for 6 treatments (days 0, 7, 14, 21,
      28, and 35). Clinical signs and results of hematologic, serum biochemical, and
      synovial fluid (SF) analyses and radiography were used to evaluate treatment
      effects. On day 49, all horses were euthanatized; gross necropsy and histologic
      examinations of internal organs and articular tissues were performed.
      Glycosaminoglycan concentration of the articular cartilage was evaluated in
      safranin O-stained sections by use of a semiquantitative microspectrophotometric
      method. RESULTS: No systemic signs were observed. Temporary mild to moderate heat
      and effusion were the only clinical signs observed in a number of joints after IA
      injections and more often only in the 100 mg group, compared with controls. The
      100 mg dose resulted in significant increases in SF WBC counts, with relative
      neutrophilia and SF total protein concentration 24 hours after injection (day 1).
      No lesions suggestive of toxic effects were detected at necropsy or on histologic
      examination. No changes in articular cartilage glycosaminoglycan concentration
      were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Six injections of 20, 60, or
      100 mg of bufexamac at weekly intervals did not cause any untoward systemic or
      local effects. These data suggest that bufexamac is a safe nonsteroidal anti
      inflammatory drug for IA administration in horses.

PMID- 11592332
TI  - Cytologic and biochemical changes associated with inoculation of amniotic fluid
      and meconium into lungs of neonatal rats.
AB  - OBJECTIVE: To evaluate the effect of homologous amniotic fluid and meconium
      inoculated intratracheally into the lungs of neonatal rats. ANIMALS: 153 male 7
      day-old Fischer-344 rats. PROCEDURE: Amniotic fluid was obtained by cesarean
      section from the uterus of pregnant rats and meconium was collected at the time
      of birth from the gastrointestinal tract of neonatal rats. Neonatal rats were
      randomly allocated into 5 treatment groups. Two groups received 0.05 ml of saline
      (0.9% NaCl) solution; the third and fourth groups received 0.05 ml of 50% or 100%
      amniotic fluid, respectively; the fifth group was inoculated with 0.05 ml of a
      20% suspension of meconium. Six or 7 rat pups/group were euthanatized by
      exsanguination under halothane anesthesia at postinoculation days 1, 3, 7, and
      14. The magnitude of injury and inflammatory response was determined by
      biochemical and cytologic analyses of bronchoalveolar lavage fluid. RESULTS:
      Inoculation with saline solution and amniotic fluid did not induce pulmonary
      injury or inflammatory response. Inoculation with meconium induced significant (P
      < 0.01) injury and inflammatory response, characterized by the release of
      cytosolic enzymes and recruitment of neutrophils in the lung. CONCLUSIONS: Saline
      solution is an innocuous vehicle that can be safely used in intratracheal
      inoculations in neonatal rats. Homologous amniotic fluid, despite containing
      keratin and epidermal cells, does not cause acute injury or inflammation in the
      lung. In contrast, meconium acts as a toxic substance injuring respiratory cells
      and causing a vigorous but transient leukocytic inflammatory reaction in the
      lungs.

PMID- 11592333
TI  - Effect of carprofen on hemostatic variables in dogs.
AB  - OBJECTIVE: To evaluate the effect of carprofen on hemostatic variables in
      clinically normal dogs. ANIMALS: 12 clinically normal Labrador Retrievers.
      PROCEDURE: 10 dogs (6 females, 4 males) received carprofen (2.2 mg/kg of body
      weight, PO, q 12 h) for 5 days. Two dogs (untreated control group; 1 female, 1
      male) did not receive carprofen. Hemostatic variables (platelet count, activated
      partial thromboplastin time, prothrombin time, fibrinogen, platelet aggregation,
      and bleeding time) were assessed for all dogs prior to treatment, on day 5 of
      treatment, and 2 and 7 days after discontinuation of the drug (days 7 and 12).
      Serum biochemical variables and Hct were assessed prior to treatment and on days
      5 and 12. RESULTS: In dogs receiving carprofen, platelet aggregation was
      significantly decreased, and onset of aggregation was significantly delayed on
      days 5, 7, and 12, compared with pretreatment values. Activated partial
      thromboplastin time was significantly increased on days 5, 7, and 12 over
      pretreatment values in treated dogs, but values remained within reference ranges.
      Significant differences were not detected in buccal mucosal bleeding time, other
      serum biochemical and hemostatic variables, or Hct, compared with pretreatment
      values and the internal control group. CONCLUSIONS AND CLINICAL RELEVANCE:
      Administration of carprofen for 5 days causes minor but not clinically important
      alterations in hemostatic and serum biochemical variables in clinically normal
      Labrador Retrievers. Carprofen is commonly used to treat osteoarthritis and
      chronic pain in dogs, but prior to this study, its effect on platelet aggregation
      and hemostatic variables was unknown.

PMID- 11592334
TI  - Calcium sensitivity of force production and myofibrillar ATPase activity in
      muscles from Thoroughbreds with recurrent exertional rhabdomyolysis.
AB  - OBJECTIVE: To determine whether the basis for recurrent exertional rhabdomyolysis
      (RER) in Thoroughbreds lies in an alteration in the activation and regulation of
      the myofibrillar contractile apparatus by ionized calcium. ANIMALS: 4
      Thoroughbred mares with RER and 4 clinically normal (control) Thoroughbreds.
      PROCEDURES: Single chemically-skinned type-I (slow-twitch) and type-II (fast
      twitch) muscle fibers were obtained from punch biopsy specimens, mounted to a
      force transducer, and the tensions that developed in response to a series of
      calcium concentrations were measured. In addition, myofibril preparations were
      isolated from muscle biopsy specimens and the maximal myofibrillar ATPase
      activity, as well as its sensitivity to ionized calcium, were measured. RESULTS:
      Equine type-I muscle fibers were more readily activated by calcium than were type
      II muscle fibers. However, there was no difference between the type-II fibers of
      RER-affected and control horses in terms of calcium sensitivity of force
      production. There was also no difference between muscle myofibril preparations
      from RER-affected and control horses in calcium sensitivity of myofibrillar
      ATPase activity. CONCLUSIONS AND CLINICAL RELEVANCE: An alteration in
      myofibrillar calcium sensitivity is not a basis for pathologic contracture
      development in muscles from RER-affected horses. Recurrent exertional
      rhabdomyolysis in Thoroughbreds may represent a novel heritable defect in the
      regulation of muscle excitation-contraction coupling or myoplasmic calcium
      concentration.

PMID- 11592335
TI  - Evaluation of ultrastructural changes associated with encephalomyocarditis virus
      in the myocardium of experimentally infected piglets.
AB  - OBJECTIVE: To evaluate the ultrastructural changes and localization of
      encephalomyocarditis virus (EMCV) and viral pathogenesis in the myocardium of
      experimentally infected piglets. ANIMALS: Eight 20-day-old piglets. PROCEDURE:
      Six piglets were inoculated oronasally with 5 ml (10(6) median tissue culture
      infective dose/ml) of EMCV suspension, and 2 were used as uninfected controls.
      Piglets were euthanatized or died between postinoculation days 1 and 3. Samples
      of heart tissue from all piglets were evaluated histologically, by virus
      isolation, and by use of immunohistochemistry and electron microscopy. RESULTS:
      All infected piglets had gross or microscopic lesions of interstitial
      myocarditis. immunohistochemically, EMCV antigen was detected in the cytoplasm of
      cardiac muscle cells, Purkinje fibers, and endothelial cells and in the nucleus
      of cardiac muscle cells and Purkinje fibers. Ultrastructural lesions were
      characterized by degeneration and necrosis of cardiac muscle cells and Purkinje
      fibers. Virus was present intracytoplasmically in cardiac muscle cells, Purkinje
      fibers, and endothelial cells of capillaries and intranuclearly in cardiac muscle
      cells. The cell membranes of the Purkinje fibers and endothelial cells had
      distinct protrusions that contained virus particles. In control piglets, no
      lesions were found, and no EMCV antigen was detected. CONCLUSIONS: Localization
      of EMCV intracytoplasmically or intranuclearly in various myocardial cells may
      well reflect the sites of viral proliferation. The presence of virus particles in
      cell membrane protrusions and in vacuoles within the lumen of capillaries
      indicates that virus is released not only by disintegration of the host cell but
      also via exocytosis.

PMID- 11592336
TI  - Effect of a valine residue at codon 352 of the VP2 capsid protein on in vivo
      replication and pathogenesis of Aleutian disease parvovirus in mink.
AB  - OBJECTIVE: To determine whether a group of 3 genetic differences in the
      nonstructural protein (NS1) or 1 genetic difference in the structural protein
      (VP2) of Aleutian disease parvovirus (ADV) is responsible for an increase in the
      in vivo replication and pathogenicity of G/U-8, a chimera of ADV-G
      (nonpathogenic) and ADV-Utah (pathogenic), compared with G/U-10. ANIMALS: 32
      eight-month-old female sapphire mink (Mustela vison). PROCEDURE: Chimeric viruses
      were constructed, propagated in vitro, and used to inoculate mink. Antiviral
      antibody responses, presence of serum viral nucleic acid, and serum gamma
      globulin concentrations were monitored for 120 days following inoculation.
      Histologic examination of the liver, kidneys, spleen, and mesenteric lymph nodes
      was performed after necropsy. RESULTS: A chimera containing only the 3 amino acid
      substitutions in NS1 did not elicit measurable responses indicative of
      replication or pathogenicity in inoculated mink. Serum antiviral antibody
      responses, frequency of detection of viral nucleic acid in serum, gamma globulin
      response, and histologic changes in mink inoculated with chimeras containing a
      valine residue at codon 352 (352V) of VP2 capsid were increased, compared with
      values from mink inoculated with chimeric viruses that did not contain 352V.
      CONCLUSIONS AND CLINICAL RELEVANCE: A valine residue at codon 352 in the VP2
      capsid protein of ADV affects in vivo viral replication and pathogenicity. This
      amino acid may be part of an incompletely defined pathogenic determinant of ADV.
      Further characterization of the pathogenic determinant may allow future
      development of focused preventive and therapeutic interventions for Aleutian
      disease of mink.

PMID- 11592337
TI  - Effects of antibiotics on morphologic characteristics and migration of canine
      corneal epithelial cells in tissue culture.
AB  - OBJECTIVE: To determine effects of commonly used ophthalmic antibiotics on
      cellular morphologic characteristics and migration of canine corneal epithelium
      in cell culture. SAMPLE POPULATION: Corneal epithelial cells harvested from
      corneas of 12 euthanatized dogs and propagated in cell culture. PROCEDURE: Cells
      were treated with various antibiotics after a defect was created in the
      monolayer. Cellular morphologic characteristics and closure of the defect were
      compared between antibiotic-treated and control cells. RESULTS: Cells treated
      with ciprofloxacin and cefazolin had the greatest degree of rounding, shrinkage,
      and detachment from plates. Cells treated with neomycin-polymyxin B-gramicidin
      and gentamicin sulfate had rounding and shrinkage but with less detachment. Cells
      treated with tobramycin and chloramphenicol grew similarly to control cells. On
      the basis of comparisons of defect circumference between control cells and cells
      exposed to antibiotics, tobramycin affected cellular migration the least.
      CONCLUSIONS AND CLINICAL RELEVANCE: Effects of ciprofloxacin and cefazolin on
      morphologic characteristics of canine corneal epithelial cells in vitro should be
      taken into consideration before using these antibiotics for first-line of
      treatment for noninfected ulcers. Of the antibiotics tested that have a primarily
      gram-negative spectrum of coverage, gentamicin inhibited corneal epithelial cell
      migration and had greater cytopathologic effects than tobramycin did. For
      antibiotics with a gram-positive coverage, chloramphenicol had no cytopathologic
      effects on cells in comparison to cefazolin, which caused most of the cells to
      shrink and detach from the plate. Polymyxin B-neomycin-gramicidin was midrange in
      its effects on cellular morphologic characteristics and migration.

PMID- 11592338
TI  - Pharmacokinetics of EF5 [2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3
      pentafluoropropyl) acetamide] in human patients: implications for hypoxia
      measurements in vivo by 2-nitroimidazoles.
AB  - OBJECTIVES: Pharmacokinetic studies were performed on the first 28 patients
      enrolled in a phase I trial to determine the ability of EF5 [2-(2-nitro-1-H
      imidazolI-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] to detect hypoxia in
      human tumors in the absence of patient toxicity. METHODS: EF5 was made in
      purified form and formulated for intravenous injection by the National Cancer
      Institute. After obtaining consent from the patients, EF5 was administered and
      blood samples were drawn at various times over approximately 48 h. For most
      patients it was possible to collect total urine at approximately 8-h intervals.
      EF5 in plasma and urine was analyzed by high-performance liquid chromatography.
      RESULTS: EF5's plasma concentration followed a simple exponential decay following
      infusion. The plasma half-life was 11.7 +/- 2.6 h (+/- SD) and was not affected
      by drug dose (9 to 28 mg/kg), fractional urine recovery, patient weight or
      gender. Absolute plasma values suggested even biodistribution of the drug
      throughout the soft tissue with a volume of distribution equal to 0.56 l/ kg.
      Despite the relatively high lipid partition coefficient (logP = 0.6), EF5 was
      excreted primarily (up to 70%) via kidney clearance. No drug metabolites (e.g.
      retaining the 2-nitroimidazole chromophore) were detected in either plasma or
      urine. No toxicity was found at drug doses adequate to detect tumor hypoxia.
      CONCLUSIONS: Currently held paradigms of 2-nitroimidazole metabolism (e.g.
      clearance rate and toxicity as affected by octanol/ water partition coefficient)
      are discussed. The results reported herein suggest that EF5 is biologically
      stable with predictable pharmacokinetics. EF5's consistent half-life and
      clearance properties will allow quantitative analysis of EF5 binding relative to
      tissue oxygen levels.

PMID- 11592339
TI  - Synergistic interaction between topotecan and microtubule-interfering agents.
AB  - PURPOSE: Topotecan is a topoisomerase I inhibitor with demonstrated anticancer
      activity in preclinical and clinical studies. The purpose of the present study
      was to evaluate drug-drug interactions in therapeutic regimens that would combine
      topotecan with microtubule-interfering agents, such as Taxol and vinblastine.
      METHODS: The cytotoxic activities of various drug combinations and schedules of
      administration were measured in a colon cancer cell line using the MTT assay.
      Western blot and flow cytometry were performed to determine the effects of Taxol
      and vinblastine on topoisomerase I and Bcl-xL protein levels and cell cycle
      distribution. RESULTS: Brief incubation of colon cancer cells with low
      concentrations of either Taxol or vinblastine increased the efficacy of a
      subsequent treatment with topotecan. Preincubation of cells with vinblastine or
      Taxol reduced by 10- to 40-fold the concentration of topotecan necessary to
      induce a 50% decrease in cell survival. The effects were maximal when the cells
      were treated for 5 h with microtubule-interfering agents and then incubated for
      19 h in drug-free medium before the addition of topotecan. Under these
      conditions, both Taxol and vinblastine caused an increase in topoisomerase I
      protein levels, fraction of S phase cells, and extent of Bcl-xL phosphorylation
      immediately prior to the addition of topotecan. All these factors may contribute
      to the increased efficacy of topotecan observed with sequential therapy.
      CONCLUSION: Combinations of topotecan and microtubule-interfering agents result
      in synergistic anticancer activity when the drugs are administered sequentially.
      The promising preclinical data presented here encourage clinical testing of these
      drug combinations using a sequential schedule of administration.

PMID- 11592340
TI  - Bioavailability study of oral and intravenous OGT 719, a novel nucleoside
      analogue with preferential activity in the liver.
AB  - PURPOSE: Although oral fluoropyrimidine prodrugs are increasingly being
      administered in preference to intravenous nucleoside analogues in cancer
      chemotherapy, their activation in malignant liver tissue may be insufficient. OGT
      719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue,
      preferentially localized in hepatocytes and hepatoma cells via the
      asialoglycoprotein receptor. The aim of this study was to assess the systemic
      bioavailability of this rationally designed drug in 16 patients with advanced
      solid cancers. METHOD: Crossover pharmacokinetic study of oral (400 or 800 mg)
      and intravenous (250 mg/m2) OGT 719. RESULTS: Linear pharmacokinetics and oral
      bioavailability of approximately 25% were observed at the dose levels used in
      this study. Like other 5-FU prodrugs, considerable interpatient variability was
      observed in bioavailability following oral dosing. The mean half-life for oral
      doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were
      demonstrated. CONCLUSION: The systemic bioavailability and half-life of oral OGT
      719 are sufficient to merit dose escalation studies with frequent daily dosing.
      Subsequent efficacy studies should be performed in patients with primary and
      secondary liver malignancies.

PMID- 11592341
TI  - Plasma pharmacokinetics and bioavailability of 1-(2-chloroethyl)-3-sarcosinamide
      1-nitrosourea after intravenous and oral administration to mice and dogs.
AB  - PURPOSE: Chloroethylnitrosoureas are among the most widely used chemotherapeutic
      agents for the treatment of brain tumors. SarCNU (1-(2-chloroethyl)3
      sarcosinamide-1-nitrosourea) is an investigational nitrosourea analogue that has
      shown greater antitumor activity and a more favorable toxicity profile than 1,3
      bis(2-chloroethyl)-1-nitrosourea in preclinical studies. The purpose of the
      present study was to characterize the plasma pharmacokinetics and oral
      bioavailability of SarCNU in mice and dogs treated by intravenous infusion and
      gastric intubation. METHODS: SarCNU was administered to mice by i.v. injection or
      orally at doses ranging from 10 to 100 mg/kg. Plasma samples were obtained from
      groups of five animals at each time-point at intervals ranging from 3 min to 2.5
      h after dosing. A group of three male beagle dogs were treated with Sar CNU 10
      mg/kg given both by i.v. infusion and orally in a crossover design. The
      concentration of SarCNU in plasma was measured by high-performance liquid
      chromatography. RESULTS: During the initial 90 min after i.v. injection to mice,
      SarCNU was eliminated from plasma in a monoexponential manner with a mean half
      life of 9.8 +/- 0.8 min. The total plasma clearance was 47.3 +/- 8.7 ml/min per
      kg and the apparent volume of distribution was 0.7 +/- 0.1 l/kg. SarCNU exhibited
      linear pharmacokinetic behavior following both i.v. and oral administration of
      doses ranging from approximately 10 to 100 mg/kg. Peak plasma levels provided by
      a dose of 100 mg/kg given by the i.v. and oral routes were 142.4 microg/ml (0.5
      min) and 27.8 microg/ml (9.8 min), respectively. The mean oral bioavailability of
      the drug was 57.3 +/- 12.6% in mice. In comparison, the disposition of SarCNU in
      dogs after rapid i.v. injection was biexponential, with half-lives of 5.4 +/- 8.4
      min and 40.8 +/- 9.0 min for the initial and terminal disposition phases,
      respectively. Mean values of the total plasma clearance and apparent volume of
      distribution were 17.8 +/- 1.8 ml/min per kg and 1.1 +/- 0.3 l/kg, respectively.
      The Cmax was 18.5 +/- 6.5 microg/ml after i.v. injection and 8.5 0.4 microg/ml
      after oral administration of a 10 mg/kg dose. Oral bioavailability of the drug in
      dogs (71.7 +/- 21.2%) was greater than that observed in mice. CONCLUSIONS: SarCNU
      exhibited linear and consistent pharmacokinetics in mice and dogs with very good
      oral bioavailability in both species. These findings support the rationale for
      evaluating SarCNU given by the oral route of administration in phase I clinical
      trials.

PMID- 11592342
TI  - Hepatic arterial and intravenous administration of 1,25-dihydroxyvitamin D3-
      evidence of a clinically significant hepatic first-pass effect.
AB  - PURPOSE: We have previously shown that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]
      inhibits the proliferation of a number of human cancers, including colorectal and
      hepatocellular carcinoma, both of which affect the liver and are major causes of
      cancer death. However, the clinical use of 1,25(OH)2D3 and analogues has been
      restricted by the development of hypercalcaemia upon systemic administration. We
      hypothesized that a clinically significant hepatic first-pass effect may exist
      upon the administration of 1,25(OH)2D3 as a hepatic arterial infusion, and that
      such an effect may allow high levels of 1,25(OH)2D3 to be delivered to the liver
      whilst avoiding high systemic levels. METHODS: To examine this hypothesis, two
      groups of Landrace pigs were given identical doses of 1,25(OH)2D3 as continuous
      infusions, one group systemically, the other as a hepatic arterial infusion.
      Serum levels of 1,25(OH)2D3, calcium, phosphate and a number of liver and kidney
      function tests were performed regularly. RESULTS: Concentrations of 1,25(OH)2D3
      and calcium remained normal in the hepatic arterial infusion animals, in contrast
      to the intravenous infusion animals which developed elevated levels of
      1,25(OH)2D3 and hypercalcaemia. Hepatic arterial infusion of 1,25(OH)2D3 did not
      produce any adverse effects upon renal or hepatic function. CONCLUSION: The
      present findings support the existence of a clinically significant hepatic first
      pass effect when 1,25(OH)2D3 is administered as a continuous hepatic arterial
      infusion. Hepatic arterial infusion of 1,25(OH)2D3 has great potential in the
      treatment of hepatic cancers.

PMID- 11592343
TI  - A phase I and pharmacologic study of 9-aminocamptothecin administered as a 120-h
      infusion weekly to adult cancer patients.
AB  - PURPOSE: To define the toxicity profile and the recommended phase II doses of 9
      aminocamptothecin (9-AC) administered as a weekly 120-h infusion. METHODS: 9-AC
      was administered over 120 h weekly to 55 adult cancer patients with solid tumors
      over doses ranging from 0.41 to 0.77 mg/m2 per day in a phase I and pharmacologic
      study. 9-AC formulated in dimethylacetamide/polyethylene glycol (DMA) was
      administered on a 3 of 4-week schedule, and the newer colloidal dispersion (CD)
      formulation was given on a 2 of 3-week schedule. RESULTS: Overall, 193 courses of
      therapy were administered over 122 dose levels. On the 3 of 4-week schedule, 9-AC
      DMA infused at > or = 0.6 mg/m2 per day for 120 h weekly produced dose-limiting
      neutropenia, thrombocytopenia, and diarrhea, or resulted in 1-2-week treatment
      delays. Shortening treatments to 2 of 3 weeks resulted in dose-limiting
      neutropenia and fatigue at infusion rates > 0.72 mg/m2 per day. The ratio of 9-AC
      lactone to total (carboxylate + lactone) drug plasma concentrations at steady
      state was 0.15 +/- 0.07. Clinical toxicities and drug pharmacokinetics were not
      substantially different between the DMA and CD formulations. One objective
      response was observed in a patient with bladder cancer and minor responses were
      observed in patients with lung and colon cancers. Plasma area under the
      concentration versus time curve for 9-AC lactone modestly correlated with the
      degree of thrombocytopenia (r=0.51) using a sigmoid Emax pharmacodynamic model.
      CONCLUSION: The recommended phase II dose for the 9-AC DMA formulation is 0.48
      mg/m2 per h over 120 h for 3 of 4 weeks and for the 9-AC CD formulation is 0.6
      mg/m2 per day over 120 h for 2 of 3 weeks. Both regimens were well tolerated and
      feasible to administer.

PMID- 11592344
TI  - Bioavailability of penclomedine and systemic exposure to 4-O-demethylpenclomedine
      in patients receiving oral and intravenous penclomedine.
AB  - PURPOSE: Oral administration of penclomedine was investigated based on
      preclinical studies indicating that an oral schedule of penclomedine treatment
      may prevent the neurotoxicity observed in phase I studies of an intravenous
      (i.v.) formulation, possibly by reducing maximum plasma concentrations (Cmax) of
      the neurotoxic parent species. METHODS: Penclomedine was administered i.v. (200
      mg/m2) and orally (250 mg/m2) in alternate sequences to patients with solid tumor
      malignancies. Plasma concentrations of parent drug and the principal metabolite,
      4-O-demethylpenclomedine, were determined by a reversed-phase HPLC assay.
      RESULTS: Penclomedine was detectable in the plasma of all patients within 1 h of
      oral penclomedine treatment and Cmax was reached within 1 to 4 h. Consistent with
      the hypothesis that an oral schedule of administration may circumvent
      neurotoxicity, a paired data analysis demonstrated a significant reduction in
      Cmax values following oral administration (P=0.017). However the magnitude of
      this reduction was highly variable. Similarly an extensive range in the relative
      exposure to both parent drug and metabolite were observed. The bioavailability of
      penclomedine ranged from 28% to 98% (median 73%). CONCLUSIONS: Oral penclomedine
      does produce systemic exposure, but substantial interpatient variability in
      absorption and systemic exposure is present which may limit the clinical role of
      the oral route of administration.

PMID- 11592345
TI  - Carboplatin and paclitaxel interact antagonistically in a megakaryoblast cell
      line--a potential mechanism for paclitaxel-mediated sparing of carboplatin
      induced thrombocytopenia.
AB  - PURPOSE: Clinical observation has shown that paclitaxel ameliorates the
      antiplatelet toxicity of carboplatin when the two drugs are combined, although
      antitumour activity and white cell toxicity are at least additive. We
      hypothesized that this is due to an interaction between the two drugs at the
      level of the platelet precursor. METHODS: We measured inhibition of growth of the
      megakaryoblast cell line MEG-01 following exposure to paclitaxel and carboplatin
      singly or combined. Drug interaction was assessed by median effect analysis.
      RESULTS: An antagonistic interaction was observed, and this was most marked at
      drug concentrations giving a low level of growth inhibition (P < 0.002, sign
      test). The interaction was not sequence-dependent. There was no significant
      difference in whole-cell accumulation of platinum or the amount of platinum
      adducts on DNA following combined treatment in comparison with carboplatin alone.
      CONCLUSIONS: These results provide the first evidence of an antagonistic
      interaction between paclitaxel and carboplatin in a platelet precursor and
      provide an explanation for the platelet-sparing effect of the combination of
      these chemotherapeutic agents. While the mechanisms underlying the interaction
      described in this report are yet to be fully elucidated, this study provides
      evidence that the antagonism between paclitaxel and carboplatin in MEG-01 cells
      is not due to reduced platination of DNA.

PMID- 11592346
TI  - Effect of probenecid on ventricular cerebrospinal fluid methotrexate
      pharmacokinetics after intralumbar administration in nonhuman primates.
AB  - PURPOSE: Intrathecal methotrexate (MTX) achieves high concentrations in the
      cerebrospinal fluid (CSF) following intralumbar administration. However, peak
      ventricular CSF MTX concentrations are highly variable and are < 10% of those
      achieved with intraventricular dosing. The objectives of this study were to
      evaluate the effect of intralumbar and intravenous probenecid on ventricular CSF
      MTX concentrations after intralumbar administration of MTX, and to compare the
      pharmacokinetics of MTX after intralumbar and intraventricular administration.
      METHODS: Nonhuman primates (Macaca mulatta) with permanently implanted catheters
      in the lateral and fourth ventricles received 0.5 mg intraventricular (lateral
      ventricle) MTX, or 0.5 mg intralumbar MTX with and without intralumbar or
      intravenous probenecid. Animals were kept prone for 1 h after MTX administration,
      and ventricular CSF was sampled up to 48 h from a fourth ventricular Ommaya
      reservoir. MTX concentrations were measured using the dihydrofolate reductase
      enzyme inhibition assay. Area under the ventricular CSF MTX concentration-time
      curve (AUC) was used as a measure of MTX exposure. RESULTS: Peak ventricular CSF
      MTX concentrations and AUCs were highly variable after intralumbar MTX
      administration. Ventricular CSF MTX AUCs increased by a mean of 3.2-fold after
      the addition of intralumbar probenecid. Intravenous administration of probenecid
      did not result in an increase in ventricular CSF MTX AUCs. Asymptomatic
      pleocytosis was observed in all animals after intralumbar probenecid
      administration. Ventricular CSF MTX concentrations and AUCs were less variable
      after intraventricular administration of MTX. CONCLUSION: The administration of
      intralumbar but not intravenous probenecid increases the ventricular CSF MTX
      exposure after intralumbar MTX administration.

PMID- 11592347
TI  - Limited sampling models for CPT-11, SN-38, and SN-38 glucuronide.
AB  - PURPOSE: We developed limited sampling models (LSMs) for predicting the area
      under the curve (AUC) of irinotecan (CPT-11) and its metabolites SN-38 and SN-38
      glucuronide (SN-38G). PATIENTS AND METHODS: Regression models were developed
      based on data from a phase I clinical trial involving 34 patients with advanced
      solid tumor malignancies who received CPT-11 as a 90-min infusion on an every 3
      week dosing schedule. Multiple stepwise regression procedures were supplemented
      by all possible subsets regression analysis. Alternative clinically based and
      empirically derived LSMs were determined via model validation assessment
      including bootstrap simulation testing. RESULTS: The best LSMs for CPT-11 AUC
      included concentrations recorded at the end of infusion and 4 h later with an
      option to include a blood draw at 7.5 h from infusion start. For SN-38 and SN-38G
      AUC, optimal LSMs included the additional metabolite concentration at 48 h after
      infusion. The LSMs were able to predict most patient AUC values to within 10% of
      the true value. CONCLUSION: CPT-11 AUC can be modeled with acceptable accuracy
      using only two or three plasma concentration time-points. A variety of LSM
      alternatives provided comparable accuracy in predicting AUC. Given the wide
      variety of LSM alternatives, clinical considerations and patient burden become
      more important performance parameters than statistical considerations for the
      choice of time-points in constructing LSMs.

PMID- 11592348
TI  - Therapeutic activity of the topoisomerase I inhibitor J-107088 [6-N-(1
      hydroxymethyla-2-hydroxyl) ethylamino-12,13-dihydro-13-(beta-D-glucopyranosyl) 
      5H-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7(6H)-dione]] against pediatric and
      adult central nervous system tumor xenografts.
AB  - PURPOSE: The in vivo antitumor activity of a novel topoisomerase I inhibitor, J
      107088, was tested in athymic nude mice bearing subcutaneous or intracranial
      pediatric and adult malignant CNS tumor-derived xenografts. METHODS: J-107088 was
      administered to animals on days 1-5 and 8-12 via intraperitoneal injection at a
      dose of 54 mg/kg (162 mg/m2) per day in 10% dimethyl sulfoxide in 0.9% saline.
      The xenografts evaluated were derived from a childhood glioblastoma multiforme (D
      456 MG), a childhood medulloblastoma (D-341 MED), an adult anaplastic astrocytoma
      (D-54 MG), an adult glioblastoma multiforme (D-245 MG), and a procarbazine
      resistant subline of D-245 MG [D-245 MG (PR)]. RESULTS: J-107088 produced
      regressions and significant growth inhibition in all five of the xenograft lines
      growing subcutaneously. Growth delays ranged from 7.6 days with D-245 MG to 62.1
      days with D-456 MG (P < 0.001). J-107088 also produced an 83% increase in
      survival in mice bearing intracranial D-456 MG (P < 0.001). CONCLUSION: These
      results indicate that J-107088 may be active in the treatment of childhood and
      adult malignant brain tumors and provide the rationale for initiation of clinical
      trials with this agent.

PMID- 11592350
TI  - Managing up, over, and across.
AB  - The challenges of managing up in a merging organization that is structured as a
      matrix and provides services to others in a network organization are described.
      Managing up in the merging organization, which may be characterized by
      instability, jockeying for position, conflicts of organizational cultures,
      inconsistent or conflicting policies, and a lack of vision, calls for the
      development of relationships, support for the merger, a focus on pharmaceutical
      care, and consideration of all factions. Managers are advised to be aware of
      shifts of power and to focus on issues rather than people when forced to take a
      "side." Identifying bosses, keeping multiple bosses satisfied, and avoiding upper
      level politics are challenges posed by managing over in the matrix organization.
      Recommended strategies include communicating with and understanding each boss,
      developing relationships, and keeping the goals and visions of the organization
      in mind. Managers in a matrix organization should remember to whom they
      ultimately report and should be honest with their primary boss about conflicts.
      Managing across may be complicated by differences in the objectives of network
      institutions, the customer-based relationship among these institutions, and the
      need for a vision that clearly recognizes mutual responsibilities. Establishing a
      relationship that benefits both institutions, tailoring services to institutions,
      specifying the services to be provided in a contract, developing relationships,
      and checking regularly on the quality of services are among the strategies for
      managing across. Services should not merely be transplanted from one institution
      to another, and relationships that are not mutually beneficial should be re
      evaluated. Specific challenges, strategies, and cautions are associated with
      managing up in a merging organization, over in a matrix organization, and across
      in a network organization, but success in any of these situations requires
      vision, a strong team, influence, a strong network of relationships, effective
      communication, the ability to focus on goals, and a history of delivering on
      promises.

PMID- 11592349
TI  - Cisplatin and escalating doses of paclitaxel and epirubicin in advanced ovarian
      cancer. A phase I study.
AB  - PURPOSE: The combination of paclitaxel and cisplatin is considered the standard
      regimen for advanced ovarian cancer (AOC). A meta-analysis has shown that the
      incorporation of anthracyclines into first-line chemotherapy might improve long
      term survival by 7-10%. We designed a phase I-II study in patients with AOC using
      a combination of a fixed dose of cisplatin with paclitaxel and epirubicin both
      given at escalating doses every 3 weeks. The objectives of this study were to
      determine both the maximum tolerated dose (MTD) and the antitumor activity of
      this combination. METHODS: Six different dose levels were planned. The starting
      doses were cisplatin 75 mg/m2, paclitaxel 140 mg/m2, and epirubicin 50 mg/m2. The
      doses of paclitaxel were escalated in 20-mg/m2 increments, alternating with 20
      mg/m2 increments of epirubicin. Ten patients with AOC entered the phase I study.
      Three patients each were enrolled at level I and level II and four patients at
      level III, and at each level, 15 courses were administered. Patients received a
      median of five courses. RESULTS: Nonhematological toxicity was generally mild,
      except for grade 3 mucositis in one course at levels II and III, and grade 3
      vomiting in one course at levels I and III. Hematological toxicities were grade 3
      4 neutropenia in 60%, 47% and 60% of courses at levels I, II and III,
      respectively, and grade 3 anemia in one course at level III. At level III two of
      four patients developed a dose-limiting toxicity which was grade 4 neutropenia
      lasting more than 1 week. CONCLUSIONS: The MTD was reached at level II with
      cisplatin 75 mg/m2, paclitaxel 160 mg/m2, and epirubicin 50 mg/m2. The phase II
      part of the study is currently ongoing.

PMID- 11592351
TI  - Managing up to maximize medicare reimbursement for outpatient care.
AB  - An example of managing up through participation in a multidisciplinary team
      tasked with maximizing reimbursement under the Medicare ambulatory patient
      classification (APC) system is described. Medicare's new system of payment for
      hospital outpatient services replaces the cost-based reimbursement model of the
      past with a technical payment based on the outpatient evaluation and management
      level. Individual institutions are responsible for developing criteria for
      defining technical visit levels. Managers at the New England Medical Center
      formed a team to develop these criteria. The team outlined components of the
      patient visit that qualified as technical costs, such as the use of space at a
      facility, medical and surgical supplies, and nonphysician professional services.
      Team members then contacted each of the center's clinics to identify specific
      services that met these criteria. After formulating the technical visit level
      criteria, the team determined who would assign the technical visit level, wrote
      policies and procedures, and trained staff. The APC team also assessed billing
      procedures, focusing particularly on the accuracy of the charge master and the
      use of proper codes and billing units for pass-through drugs. The team continues
      to monitor its results by reviewing payments received from Medicare and auditing
      high-risk areas. The APC team used the principles of managing up to maximize
      Medicare reimbursement for outpatient visits.

PMID- 11592352
TI  - Operational and financial principles of managing up.

PMID- 11592353
TI  - Persuasion as a strategy for managing up.
AB  - Managing up and the effective use of persuasion are described. Managing up
      involves the use of relationships built on respect, understanding, and effective
      communication. Persuasion is an important strategy for managing up; its elements
      include establishing credibility, framing goals on common ground, vividly
      reinforcing your position, and connecting emotionally. Persuasive strategies that
      should be avoided include using hard-sell tactics, refusing to compromise,
      relying on strong arguments alone, surprising the boss in front of others, and
      assuming that persuasion is a one-shot effort. The use of supporting data helps
      establish credibility. Anticipating important data elements and locating
      published outcome data and experience at peer institutions that support a
      proposed plan of action increase the likelihood of the plan's acceptance. The
      plan and supporting data should be presented clearly and concisely. Once a
      proposal is approved, delivering what has been promised and following through
      with measurements of effectiveness are critical for enhancing credibility and
      increasing the likelihood of future successes. Persuasion is one key to working
      synergistically with an organization's upper-level management.

PMID- 11592354
TI  - Managing up in times of financial crisis.
AB  - The use of managing up in an institution's time of financial crisis is described.
      The goals of crisis management include survival, maintaining quality and service,
      learning issues and impacts, supporting the team, and preparing for the aftermath
      as the crisis subsides. Survival calls for a commitment by leaders to remain
      focused, and to maintain and support the management team. Pharmacy directors must
      be able to adapt to chaos and to the limited information disseminated by senior
      leadership. Identifying the underlying cause of the crisis, which may not be
      directly related to the measures taken to resolve it, is also critical to
      survival. Among the keys to maintaining quality and service are keeping the staff
      focused on patient care and maintaining credibility by sharing all information
      that is available. Pharmacy directors need to maintain the confidence of their
      staff members and to encourage them to do the best they can with the resources
      available. Taking the initiative to acquire appropriate data, to translate that
      data into relevant information, and to seek benchmarks for comparison is also
      important. Once the crisis has passed, attention must be given to updating and
      maintaining databases, supporting the staff, and improving morale. Scenario
      planning can help identify measures that might be taken if another crisis should
      develop. Using principles of managing up can prepare pharmacy directors for
      optimal response to an institutional financial crisis.

PMID- 11592355
TI  - The bone and joint decade: a catalyst for progress.

PMID- 11592356
TI  - Rheumatology and the health of the workforce.

PMID- 11592357
TI  - Demyelinating and neurologic events reported in association with tumor necrosis
      factor alpha antagonism: by what mechanisms could tumor necrosis factor alpha
      antagonists improve rheumatoid arthritis but exacerbate multiple sclerosis?

PMID- 11592358
TI  - Two-year, blinded, randomized, controlled trial of treatment of active rheumatoid
      arthritis with leflunomide compared with methotrexate. Utilization of Leflunomide
      in the Treatment of Rheumatoid Arthritis Trial Investigator Group.
AB  - OBJECTIVE: Three 6-12-month, double-blind, randomized, controlled trials have
      shown leflunomide (LEF; 20 mg/day, loading dose 100 mg x 3 days) to be effective
      and safe for the treatment of rheumatoid arthritis (RA). This analysis of the
      North American trial assessed whether the clinical benefit evident at month 12
      was sustained over 24 months of treatment with LEF as compared with the efficacy
      and safety of methotrexate (MTX), an equivalent disease-modifying antirheumatic
      drug, at 24 months. METHODS: The year-2 cohort, comprising patients continuing
      into the second year of treatment with > or = 1 dose of study medication and > or
      = 1 followup visit after week 52, consisted of 235 patients (LEF n = 98; placebo
      n = 36; MTX n = 101). The mean (+/- SD) maintenance dose of LEF was 19.6 +/- 1.99
      mg/day in year 2 and that of MTX was 12.6 +/- 4.69 mg/week. Statistical analyses
      used an intent-to-treat (ITT) approach. Statistical comparisons of the active
      treatments only were prospectively defined in the protocol. RESULTS: In total,
      85% and 79% of LEF and MTX patients, respectively, who entered year 2 completed
      24 months of treatment. From month 12 to month 24, the American College of
      Rheumatology improvement response rates of > or = 20% (LEF 79% versus MTX 67%; P
      = 0.049), > or = 50% (LEF 56% versus MTX 43%; P = 0.053), and > or = 70% (LEF 26%
      versus MTX 20%; P = 0.361) were sustained in both of the active treatment groups.
      The mean change in total Sharp radiologic damage scores at year 2 compared with
      year 1 and baseline (LEF 1.6 versus MTX 1.2) showed statistically equivalent
      sustained retardation of radiographic progression in the active treatment groups.
      Maximal improvements evident at 6 months in the Health Assessment Questionnaire
      (HAQ) disability index (HAQ DI) and the physical component score of the Medical
      Outcomes Survey 36-item short form were sustained over 12 months and 24 months;
      improvement in the HAQ DI with LEF4(-0.60) was statistically significantly
      superior to that with MTX (-0.37) at 24 months (P = 0.005). Over 24 months in the
      ITT cohort, serious treatment-related adverse events were reported in 1.6% of the
      LEF-treated patients and 3.7% of the MTX-treated patients. Frequently reported
      adverse events included upper respiratory tract infections, diarrhea, nausea and
      vomiting, rash, reversible alopecia, and transient liver enzyme elevations.
      CONCLUSION: The safety and efficacy of LEF and MTX were maintained over the
      second year of this 2-year trial. Both active treatments retarded radiographic
      progression over 24 months. LEF was statistically significantly superior to MTX
      in improving physical function as measured by the HAQ DI over 24 months of
      treatment. Results indicate that LEF is a safe and effective initial treatment
      for active RA, with clinical benefit sustained over 2 years of treatment without
      evidence of new or increased toxicity.

PMID- 11592359
TI  - Control of rheumatoid arthritis by oral tolerance.
AB  - OBJECTIVE: Previous randomized controlled trials for treatment of rheumatoid
      arthritis (RA) with acid-soluble chicken and bovine type II collagen (CII) have
      produced conflicting results. This randomized, double-blind, controlled trial
      examined the therapeutic effect of bovine CII tablets in RA. METHODS: CII tablets
      were prepared by adsorption onto a lactose base. Patients with a duration of RA
      of > or = 2 years and who had failed treatment with at least 1 slow-acting drug
      were recruited, provided that they had active arthritis. Patients were randomly
      assigned to receive either 0.05 mg, 0.5 mg, or 5 mg of CII or placebo daily for 6
      months. All slow-acting drugs were stopped at least 4 weeks before starting CII,
      although prednisolone was permitted at dosages < 10 mg/day. Clinical assessments
      were performed at screening and at 0, 1, 4, 8, 12, 16, 20, and 24 weeks of
      treatment. RESULTS: Fifty-five patients were recruited. Initially, there were no
      significant differences in mean Disease Activity Scores between groups. At 24
      weeks, there was a significant difference (P = 0.041, by Kruskal-Wallis analysis
      of variance); the major components of this difference were attributable to
      relatively large decreases in the 0.5 mg CII group (19% of initial values) and to
      minimal decreases in patients receiving placebo (3% of initial values). Twenty
      patients had American College of Rheumatology 20% responses; 11 of these were in
      the 0.5 mg CII group and 3 were in each of the other groups, a significant
      difference (chi2 = 14.6, P = 0.002). There was no significant difference in any
      clinical measure between the placebo, 0.05 mg CII, and 5 mg CII groups. There
      were no side effects associated with CII treatment. CONCLUSION: Treatment with
      0.5 mg/day of bovine CII is well tolerated and produces small, but significant,
      disease improvement in RA. However, the therapeutic window is narrow. The
      difference between our results and those of other trials may relate to the dose,
      species, and formulation of the CII.

PMID- 11592360
TI  - Morbidity and mortality in rheumatoid arthritis patients with prolonged and
      profound therapy-induced lymphopenia.
AB  - OBJECTIVE: Therapies that deplete lymphocytes often improve symptoms in patients
      with otherwise refractory autoimmune disease but may result in long-term
      lymphopenia, the consequences of which are uncertain. To assess the impact of
      prolonged lymphopenia on morbidity and mortality, we studied patients who had
      previously received lymphocytotoxic monoclonal antibody (mAb) therapy for
      rheumatoid arthritis (RA). METHODS: Fifty-three patients who received the
      lymphocytotoxic mAb CAMPATH-1H between 1991 and 1994 in the United Kingdom were
      assessed for mortality and infectious and malignant morbidity, by interview and
      case-note review. In addition, patients were monitored via the National Health
      Service Central Registry, to verify notification of death. Peripheral blood
      lymphocyte subsets were analyzed by flow cytometry. A retrospective, matched
      cohort study of mortality was also performed with 102 control subjects selected
      from the European League Against Rheumatism database, which comprises patients
      with rheumatic disorders who have received immunosuppressive drugs. RESULTS:
      There was profound and persistent peripheral blood lymphopenia in the mAb-treated
      patients, affecting predominantly the CD4+ subset. Median CD4+, CD8+, and CD19+
      peripheral blood lymphocyte counts at 73-84 months after therapy were 185
      cells/microl, 95 cells/microl, and 115 cells/microl, respectively. At a median
      followup of 71 months (range 14-90), 13 patients had died (24.5%), compared with
      18% of the matched controls, providing a mortality rate ratio of 1.45 (95%
      confidence interval 0.65-3.13). During 283 patient-years of followup, there were
      36 infections classified as major (12.7 per 100 patient-years). The causes of
      death and the spectrum of infections documented were similar to those expected in
      a hospital-based RA cohort. Patients who received more than 1 course of therapy
      had more severe lymphopenia than did patients who received a single course, but
      this did not have an impact on mortality or morbidity. CONCLUSION: Despite the
      occurrence of profound and long-lasting lymphopenia following treatment with
      antilymphocyte mAb therapy for RA, this therapy is not associated with a large
      excess of mortality nor with an unusual spectrum of infections, at least during a
      medium-term period of followup. These data are also relevant to patients
      receiving lymphocytotoxic mAb therapy for other indications, and to patients
      receiving other lymphodepleting therapies such as autologous stem cell
      transplantation.

PMID- 11592361
TI  - The relationship between disease activity, joint destruction, and functional
      capacity over the course of rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the relationship between functional capacity, disease
      activity, and joint destruction over the course of rheumatoid arthritis (RA).
      METHODS: The followup data on 378 patients with early RA (duration <1 year),
      included in an open, prospective study since 1985 at the Department of
      Rheumatology of the University Medical Center Nijmegen, were used. Functional
      capacity, disease activity, and joint destruction were assessed using the Health
      Assessment Questionnaire disability index (HAQ DI), the Disease Activity Score
      (DAS), and a modification of the sharp radiographic damage score, respectively.
      Multiple linear regression was used to model the data collected at 0, 3, 6, and 9
      years after study start, to investigate which variables influenced functional
      capacity during the disease course. A general linear mixed model for longitudinal
      data, which included the variables identified as significant in the multiple
      linear regression models and several interaction terms between the variables, was
      run. RESULTS: On average, the functional capacity of the patients, as measured by
      the HAQ DI, worsened over the course of the disease after an initial improvement.
      After an initial reduction in the extent of disease activity, the mean DAS
      remained more or less stable over the course of the disease. The mean modified
      sharp joint damage score worsened over the course of the disease, with a slower
      progression rate later in the disease. In the multiple linear regression at 0, 3,
      and 6 years after study start, disease activity was found to be an important
      factor influencing functional capacity, and at 6 and 9 years, joint damage had an
      important effect on functional capacity. Furthermore, at 6 and 9 years, there was
      an interaction effect of joint destruction with disease activity. In the general
      linear mixed model, disease activity, joint damage, and an interaction effect of
      disease activity and joint damage were the main factors explaining functional
      capacity. CONCLUSION: The effect of disease activity and joint destruction on
      functional capacity changes over the course of the disease. In early RA,
      functional capacity is most associated with disease activity, and in late
      disease, with joint damage.

PMID- 11592362
TI  - Power Doppler ultrasonography for assessment of synovitis in the
      metacarpophalangeal joints of patients with rheumatoid arthritis: a comparison
      with dynamic magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the effectiveness of power Doppler ultrasonography (PDUS)
      for assessing inflammatory activity in the metacarpophalangeal (MCP) joints of
      patients with rheumatoid arthritis (RA), using dynamic magnetic resonance imaging
      (MRI) as a reference method. METHODS: PDUS and dynamic MRI were performed on 54
      MCP joints of 15 patients with active RA and on 12 MCP joints of 3 healthy
      controls. PDUS was performed with a LOGIQ 500 unit by means of a 7-13-MHz linear
      array transducer. Later the same day, MRI was performed with a 1.0T MR unit. A
      series of 24 coronal T1-weighted images of the second through the fifth MCP
      joints was obtained, with intravenous injection of gadolinium
      diethylenetriaminepentaacetic acid after the fourth image (dynamic MRI). From the
      MR images, the rate of early synovial enhancement (RESE; defined as the relative
      enhancement per second during the first 55 seconds postinjection) was calculated
      and compared with the flow signal on PDUS, which was scored as present or absent.
      RESULTS: In RA patients, flow signal on PDUS was detected in 17 of 54 MCP joints
      examined. Postcontrast MR images revealed an RESE of > or = 1.0%/second in 18 of
      54 RA MCP joints. PDUS showed no flow in 47 of 48 MCP joints with an RESE of
      <1.0%/second and revealed flow in 16 of 18 MCP joints with an RESE of > or =
      1.0%/second. Using dynamic MRI as a reference, PDUS had a sensitivity of 88.8%
      and a specificity of 97.9%. CONCLUSION: PDUS was reliable for assessing
      inflammatory activity in the MCP joints of RA patients, using dynamic MRI as the
      standard. PDUS and clinical assessment of joint swelling/tenderness were only
      weakly correlated.

PMID- 11592363
TI  - Matrix metalloproteinase 9, apoptosis, and vascular morphology in early
      arthritis.
AB  - OBJECTIVE: To examine matrix metalloproteinase 9 (MMP-9) in the synovial fluid
      (SF) and synovial membrane (SM) in relation to vascular endothelial cell (EC)
      apoptosis, vascular endothelial growth factor (VEGF), and SM vascular pattern.
      METHODS: Thirty-four patients underwent needle arthroscopy of the knee joint; 12
      had early rheumatoid arthritis (RA), 12 had early psoriatic arthritis (PsA), and
      10 had osteoarthritis (OA). The early RA and early PsA patients were matched for
      disease activity. SF levels of MMP-9 and VEGF were measured by an enzyme-linked
      immunosorbent assay, and EC apoptosis was measured by TUNEL assay. MMP-9
      expression was examined in SM by immunohistochemistry. Synovial tissue explants
      were stimulated with VEGF, and MMP-9 levels were measured in the supernatants.
      The synovial vascular pattern was recorded. RESULTS: SF MMP-9 levels were
      significantly higher in early PsA patients than in early RA patients; OA patients
      had minimal levels. MMP-9 levels correlated with blood vessel morphology and SF
      VEGF levels. MMP-9 expression was greater in early PsA SM than in early RA SM,
      but the difference was not significant. In contrast however, EC apoptosis was
      greater in early RA SM than in early PsA SM. MMP-9 levels increased 2-fold and 9
      fold, respectively, in SM explant culture supernatants on day 7 in response to
      stimulation with 25 ng/ml and 50 ng/ml of VEGF. CONCLUSION: SF MMP-9 levels
      correlate with the pattern of SM neovascularization and SF VEGF levels in early
      inflammatory arthritis, and VEGF increases MMP-9 production by SM. Endothelial
      cell apoptosis, however, appears to be more prevalent in early RA. This
      combination of factors may explain the pattern of differential angiogenesis in
      these arthritides.

PMID- 11592364
TI  - Presence of a population of CD20+, CD38- B lymphocytes with defective
      proliferative responsiveness in the synovial compartment of patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To provide a comprehensive understanding of the humoral immune
      response that takes place at the site of inflammation in rheumatoid arthritis
      (RA), we studied the functional properties of synovial B cells. In particular,
      the response to various modes of mitogen stimulation was investigated. METHODS:
      Purified synovial fluid (SF) B cells were cultured in the presence of CD40 ligand
      (CD40L)-expressing fibroblasts and cytokines, activated T cells, or phorbol
      myristate acetate (PMA)/ionomycin. Proliferation was determined by 3H-thymidine
      incorporation. Release of intracellular calcium was studied by flow cytometry.
      RESULTS: The inflamed joints of RA patients contained a population of CD20+,CD38-
      B cells with dramatically impaired mitogen responsiveness. Although the Ig
      producing capacity was intact, these cells failed to proliferate in response to
      (a) CD40 in the presence of interleukin-2 (IL-2) and IL-10, (b) activated T
      cells, or (c) stimulation via the B cell receptor. Moreover, SF CD20+,CD38- B
      cells revealed a defective B cell receptor-induced Ca2+ influx, reminiscent of
      anergic B cells. Release of intracellular Ca2+ by ionomycin in the presence of
      the protein kinase C activator PMA did not restore the proliferative capacity.
      These findings indicate blockades in the proximal and distal intermediates
      involved in mitogen signaling. CONCLUSION: SF CD20+,CD38- B cells have
      functionally impaired proliferative responsiveness. The capacity of these cells
      to respond to activation by the production of Ig supports the notion that these
      cells might serve as Ig-producing effector cells and, as such, play a role in the
      pathophysiology of RA.

PMID- 11592365
TI  - Epitope specificity of clonally expanded populations of CD8+ T cells found within
      the joints of patients with inflammatory arthritis.
AB  - OBJECTIVE: To investigate the hypothesis that clonality of synovial T cells from
      patients with rheumatoid arthritis is at least partly due to the presence of
      virus-specific T cells expressing a restricted repertoire of T cell receptors
      (TCRs). METHODS: Using fluorescently labeled HLA class I-peptide tetramers,
      populations of virus-specific CD8+ T cells were identified in samples of
      peripheral blood and synovial fluid taken from 4 patients with inflammatory
      arthritis. The TCR repertoire of the virus-specific T cells in the synovial fluid
      was analyzed using a panel of TCR beta variable region-specific monoclonal
      antibodies. Where T cells expressing a particular Vbeta chain dominated the
      response to a viral epitope, the sequences of these Vbeta chains were derived
      from sorted populations of antigen-specific T cells by reverse transcription
      polymerase chain reaction. RESULTS: CD8+ T cells specific for Epstein-Barr virus,
      cytomegalovirus, and influenza virus were enriched in synovial fluid compared
      with peripheral blood. Clonal or oligoclonal populations of CD8+ T cells were
      found to dominate the responses to these viral epitopes in synovial fluid.
      CONCLUSION: The results support the hypothesis that restricted T cell receptor
      usage by large populations of virus-specific T cells provides one explanation for
      the presence of clonally expanded CD8+ T cells within the joints of patients with
      inflammatory arthritis. Thus, T cell clonality at a site of inflammation may
      reflect enrichment for memory T cells specific for foreign antigens, rather than
      proliferation of autoreactive T cells specific for self antigens.

PMID- 11592366
TI  - Highly enhanced expression of the disintegrin metalloproteinase MDC15
      (metargidin) in rheumatoid synovial tissue.
AB  - OBJECTIVE: The aim of the study was to analyze the expression of the disintegrin
      metalloproteinase MDC15 (metargidin, or ADAM15) at the messenger RNA (mRNA) and
      protein levels in synovial tissue from osteoarthritis (OA) and rheumatoid
      arthritis (RA) patients compared with normal specimens. METHODS: Conventional
      immunohistochemistry and confocal laser scanning microscopy of
      immunofluorescently stained sections, as well as in situ hybridization
      experiments and reverse transcription-polymerase chain reaction were performed
      for analyses of MDC15 expression on normal, OA, and RA synovial tissue specimens.
      RESULTS: In normal synovium, MDC15 expression was detectable at a very low level.
      MDC15 expression was considerably increased in OA-derived tissue samples, whereas
      a maximum of signal intensity for MDC15 mRNA and protein was seen in the RA
      lining layer. The CD68+ macrophage-like synoviocytes (type A) and the CD68-
      fibroblast-like synoviocytes (type B) were positive for MDC15. Moreover, a very
      strong expression of MDC15 was also found in CD138+ plasma cells in all RA
      tissues as well as in OA specimens that contained areas of mononuclear cell
      infiltrates. CD20+ B cells and CD4+ and CD8+ T cells, however, did not exhibit
      expression of MDC15, either in the synovial tissue in situ or in preparations of
      circulating lymphocytes made from the peripheral blood of RA patients or healthy
      controls. CONCLUSION: Our results demonstrate high levels of MDC15 expression in
      macrophage-like and fibroblast-like synoviocytes as well as in plasma cells as a
      histologic feature most prominent in RA synovial tissue compared with normal or
      OA synovial tissue. This suggests a potential role of MDC15 in the pathogenesis
      of cartilage destruction in inflammatory joint disease.

PMID- 11592367
TI  - Raised serum vascular endothelial growth factor levels are associated with
      destructive change in inflammatory arthritis.
AB  - OBJECTIVE: To determine whether elevated levels of the angiogenic cytokine
      vascular endothelial growth factor (VEGF), detected on presentation to an early
      arthritis clinic, are associated with the development of chronic and erosive
      arthritis. METHODS: Concentrations of VEGF and its soluble receptor, soluble fms
      like tyrosine kinase 1 (sFlt-1), were measured by enzyme-linked immunosorbent
      assay in serum samples from patients with early (<2 years from onset) arthritic
      symptoms in the peripheral joints, namely early rheumatoid arthritis (RA), self
      limiting arthritis (viral, reactive, and idiopathic inflammatory arthritis), or
      psoriatic arthritis. In addition, measurements were made in random samples from
      patients with longstanding (>3 years from symptom onset) RA treated with disease
      modifying antirheumatic drugs, from patients with osteoarthritis (OA), and from
      patients with polyarthralgia without arthritis, as well as from nonarthritic
      controls. RESULTS: Serum VEGF levels at presentation were elevated in patients
      with inflammatory arthritis (RA, psoriatic, and self-limiting arthritis) as well
      as in patients with OA, in comparison with nonarthritic controls. Moreover, serum
      VEGF concentrations were significantly higher in patients with early RA than in
      patients with self-limiting arthritis. Serum VEGF levels at presentation in
      patients with early RA correlated significantly with the development of
      radiographic damage after 1 year. Improvement in the clinical symptoms of RA was
      associated with a reduction in serum VEGF levels. Serum sFlt-1 levels were raised
      in patients with early and longstanding RA and in those with self-limiting
      arthritis, and correlated positively with the serum VEGF concentrations in
      patients with inflammatory arthritis. CONCLUSION: These findings implicate the
      proangiogenic cytokine VEGF in the persistence of inflammatory arthritis, and
      support the hypothesis that expansion of the synovial vasculature is important
      for the development of joint destruction in RA.

PMID- 11592368
TI  - Comparison of the prevalence of knee osteoarthritis between the elderly Chinese
      population in Beijing and whites in the United States: The Beijing Osteoarthritis
      Study.
AB  - OBJECTIVE: To estimate the prevalence of radiographic and symptomatic knee
      osteoarthritis (OA) in a population-based sample of elderly subjects in Beijing,
      China and compare it with that reported in the Framingham (Massachusetts) OA
      Study. METHODS: We recruited a sample of persons age > or = 60, using door-to
      door enumeration in randomly selected neighborhoods in Beijing. Subjects
      completed a home interview including questions on knee symptoms and a hospital
      examination including knee radiographs obtained during weight bearing. The
      protocol was identical to that used in the Framingham OA Study. A reader read
      intermingled Beijing and Framingham Study films to ensure high reliability. We
      defined a subject as having radiographic knee OA when the Kellgren/Lawrence grade
      was > or = 2 in at least 1 knee. Symptomatic knee OA was recorded as present when
      knee pain was reported and the symptomatic knee had radiographic OA. We estimated
      the prevalence of these entities in elderly subjects in Beijing and compared it
      with OA prevalence in Framingham, using an age-standardized prevalence ratio.
      RESULTS: Of 2,180 age-eligible Beijing subjects contacted, knee radiographs were
      obtained in 1,787 (82.0%). The prevalence of radiographic knee OA was 42.8% in
      women and 21.5% in men. Symptomatic knee OA occurred in 15.0% of women and 5.6%
      of men. Compared with women of the same age in Framingham, women in Beijing had a
      higher prevalence of radiographic knee OA (prevalence ratio 1.45, 95% confidence
      interval 1.31-1.60) and of symptomatic knee OA (prevalence ratio 1.43, 95%
      confidence interval 1.16-1.75). The prevalence of knee OA in Chinese men was
      similar to that in their white US counterparts (for radiographic OA, prevalence
      ratio 0.90; for symptomatic OA, prevalence ratio 1.02). CONCLUSION: Using
      identical methods and definitions to evaluate the prevalence of OA across
      populations, we found, surprisingly, that older Chinese women have a higher
      prevalence of knee OA than women in Framingham, Massachusetts. The prevalence in
      men was comparable. Possible explanations for these differences range from
      genetic differences to heavy physical activity among Chinese.

PMID- 11592369
TI  - Magnetic resonance imaging-based assessment of cartilage loss in severe
      osteoarthritis: accuracy, precision, and diagnostic value.
AB  - OBJECTIVE: To examine the in vivo accuracy and precision of magnetic resonance
      imaging (MRI)-based assessment of cartilage loss in patients with severe
      osteoarthritis (OA) of the knee. METHODS: High-resolution MRI images of the
      tibial cartilage were obtained in 8 patients prior to total knee arthroplasty,
      using a water-excitation gradient-echo MRI sequence (acquisition time 6 minutes
      19 seconds; spatial resolution 1.2 x 0.31 x 0.31 mm3). The MRI measurements were
      repeated after joint repositioning. The precision of the cartilage volume and
      thickness computations was determined after 3-dimensional reconstruction. During
      surgery, the tibial plateaus were resected, and the MRI data were compared with
      water displacement of surgically retrieved cartilage. RESULTS: The standard
      deviation (coefficient of variation) of repeated tibial cartilage volume
      measurements was 56 mm3 (5.5%) medially and 59 mm3 (3.8%) laterally. The
      deviation from surgically removed tissue was -13%, on average, with a high linear
      correlation between both methods (r = 0.98). In patients with varus OA, the
      tissue loss was estimated to be 1,290 mm3 in the medial tibia and 1,150 mm3 in
      the lateral tibia, compared with the data in healthy volunteers. CONCLUSION:
      Noninvasive quantitative MRI-based analysis of cartilage morphometry in severe OA
      is accurate, precise, and displays high potential diagnostic value.

PMID- 11592370
TI  - Interleukin-1, tumor necrosis factor alpha, and interleukin-17 synergistically up
      regulate nitric oxide and prostaglandin E2 production in explants of human
      osteoarthritic knee menisci.
AB  - OBJECTIVE: In osteoarthritis (OA), a combination of biochemical and biomechanical
      factors may damage both menisci and articular cartilage. Nitric oxide (NO) and
      prostaglandin E2 (PGE2) have been implicated as mediators of inflammation in OA.
      The goals of this study were to determine if menisci from patients with OA
      produce NO and PGE2, and if the proinflammatory cytokines interleukin-1beta (IL
      1beta), tumor necrosis factor a (TNFalpha), and IL-17 augment NO and PGE2
      production by these tissues. METHODS: Menisci were obtained from 17 patients (age
      47-75 years) undergoing total knee replacement for OA. Tissue explants were
      cultured alone or with IL-1beta, IL-17, or TNFalpha, and the release of NO and
      PGE2 from the tissue as well as the presence of type 2 nitric oxide synthase
      (NOS2) and cyclooxygenase 2 (COX-2) antigens were measured. RESULTS: All menisci
      constitutively produced NO, and significant increases in NO production were
      observed in the presence of IL-1beta, TNFalpha, or IL-17 (P < 0.05). The
      combination of IL-17 and TNFalpha significantly increased NO production compared
      with either cytokine alone. Basal and cytokine-stimulated NO synthesis was
      inhibited by the NOS inhibitors NG-monomethyl-L-arginine or N-3
      aminoethylbenzylacetamidine (1400W). IL-1beta significantly increased PGE2
      production. The combination of IL-1beta and TNFalpha had an additive effect on
      PGE2 production, while addition of IL-17 to TNFalpha or IL-1beta synergistically
      enhanced PGE2 production. Inhibition of NO production by 1400W significantly
      increased IL-1beta-stimulated PGE2 production, and inhibition of PGE2 production
      by the COX-2 inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide
      significantly increased IL-17-stimulated NO production. CONCLUSION: Menisci from
      humans with OA spontaneously produced NO and PGE2 in a manner that was
      synergistically or additively augmented by cytokines. NO and PGE2 exhibited
      reciprocal regulatory effects on one another, suggesting that pharmaceutical
      agents designed to inhibit NOS2 or COX-2 production may in fact be influencing
      both pathways.

PMID- 11592371
TI  - Activation of procollagenases is a key control point in cartilage collagen
      degradation: interaction of serine and metalloproteinase pathways.
AB  - OBJECTIVE: Bovine and human cartilages in explant culture respond to
      proinflammatory cytokines with the up-regulation of procollagenases. In
      stimulated bovine nasal cartilage (BNC), >90% of collagen is released by day 14
      of culture, but collagen release is rarely seen before day 7. The aim of this
      study was to investigate if activation of procollagenases is a rate-limiting step
      in cartilage collagen breakdown. METHODS: BNC and human articular cartilage
      explants were cultured with interleukin-1alpha (IL-1alpha) and/or oncostatin M
      (OSM) with or without test reagents. Collagen levels were determined by assay of
      hydroxyproline. Collagenase activity was measured using the diffuse fibril assay.
      RESULTS: The addition of procollagenase activators, matrix metalloproteinase 3
      (MMP-3), and APMA to IL-1alpha/OSM-stimulated BNC resulted in early release of
      collagen. The release with APMA was completely blocked by the addition of tissue
      inhibitor of metalloproteinases 1. This shows that procollagenases are present
      early in the culture period, but cartilage collagen breakdown does not happen
      until activation occurs. The addition of plasminogen to IL-1alpha/OSM-stimulated
      cartilage produced early collagen release in bovine and a significant increase in
      human cartilage. Thus, plasminogen activators (PAs) are present and convert
      plasminogen to plasmin, a known activator of several MMPs, including
      collagenases. Addition of alpha1-proteinase inhibitor or a urokinase-type PA
      inhibitor, 7-amino-4-chloro-3-(3-isothiureidopropoxy) isocoumarin, partially
      blocked the breakdown of collagen from IL-1alpha/OSM-treated bovine cartilage.
      This suggests that serine proteinases are involved in the activation cascades of
      procollagenases that result in cartilage collagen breakdown. CONCLUSION: The
      activation of procollagenases is a key control point in cartilage collagen
      breakdown, and serine proteinase pathways activate MMPs.

PMID- 11592372
TI  - Predominance of Th1 immune response in diffuse proliferative lupus nephritis.
AB  - OBJECTIVE: Lupus nephritis, which shows various histologic patterns, is a serious
      complication of systemic lupus erythematosus (SLE). We previously demonstrated
      the importance of Thl cell-mediated immune response in patients with diffuse
      proliferative lupus nephritis (DPLN). The aim of this study was to examine the
      relationship between the peripheral blood Th1/Th2 balance and the intrarenal
      immune response. METHODS: The Th1:Th2 ratio in peripheral blood was measured by
      intracellular staining for cytokines with flow cytometry. Immunohistochemical
      analysis of renal biopsy specimens was performed to clarify the characterization
      of local infiltrating cells in 3 groups of subjects: SLE patients with World
      Health Organization (WHO) class IV nephritis (DPLN) (group I; n = 13), SLE
      patients with WHO class V nephritis (group II; n = 9), and patients with minor
      glomerular lesions (group III; n = 7). In addition, the histologic activity index
      and chronicity index were evaluated and correlated with the Th1:Th2 ratio.
      RESULTS: Immunohistochemical studies showed higher numbers of CD68+ macrophages,
      CD3 + T cells, and interferon-gamma-positive cells in group I than in groups II
      or III. Renal tissues from patients in group I also showed up-regulation of
      expression of osteopontin and CD40, with a small number of infiltrating T cells
      expressing interleukin-4. Overall, the Thl:Th2 ratio in group I patients (SLE
      with DPLN) was high and correlated significantly with the histologic activity
      index, but not with the chronicity index. CONCLUSION: We have identified a
      predominance of Thl-type response in both peripheral and renal tissues of
      patients with DPLN, suggesting that the peripheral blood Thl:Th2 ratio directly
      reflects the local histopathologic findings. In patients with lupus nephritis,
      the peripheral blood Th1:Th2 ratio could be useful as a parameter that reflects
      the renal histologic activity or the strength of the local Thl response.

PMID- 11592373
TI  - Microchimerism in a female patient with systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a serious multisystem disease that has a
      striking propensity to affect women. The cause of SLE remains elusive.
      Fetomaternal cell trafficking, or the passage of fetal cells into the maternal
      circulation, is now a well-established phenomenon. In addition, fetal cells have
      been implicated in the development of preeclampsia and in the pathogenesis of
      scleroderma. We undertook this study to determine whether fetomaternal cell
      trafficking might also be involved in pathogenic processes in SLE. Fluorescence
      in situ hybridization analysis was performed using X and Y chromosome-specific
      probes on affected and unaffected tissue obtained at autopsy from a woman who had
      previously given birth to 2 males and who had died of complications of SLE. The
      goal of the analysis was to detect the presence of male cells of putative fetal
      origin. Male cells were found in every histologically abnormal tissue type that
      was examined, but were not found in histologically normal tissue. These data
      suggest that fetal cells may be associated with SLE. It is unclear whether their
      presence may be related to disease causation, an effect of disease progression,
      or unrelated to disease pathology. However, this case study is an important step
      toward understanding the potential relationship between fetomaternal cell
      trafficking and SLE pathology.

PMID- 11592374
TI  - Clinical images: Libman-Sacks endocarditis.

PMID- 11592375
TI  - Efficacy of etanercept in the treatment of the entheseal pathology in resistant
      spondylarthropathy: a clinical and magnetic resonance imaging study.
AB  - OBJECTIVE: To determine the effect of tumor necrosis factor alpha (TNFalpha)
      blockade with etanercept on the clinical manifestations of resistant
      spondylarthropathy (SpA) and on axial and peripheral entheseal lesions using
      magnetic resonance imaging (MRI). METHODS: We performed a descriptive
      longitudinal study of 10 SpA patients, all of whom had active inflammatory back
      pain and peripheral involvement. Patients were treated with 25 mg subcutaneous
      etanercept twice weekly for 6 months. Clinical assessments included entheseal
      count, visual analog scale (VAS) scores for spinal pain during the day and night,
      VAS scores for entheseal pain, the Bath Ankylosing Spondylitis Functional Index
      (BASFI), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the
      Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. MRI scans of
      sacroiliac (SI) joints, the lumbar spine, and affected peripheral joints were
      performed using a 1.5T scanner employing T1-weighted, T2-weighted fat-suppressed
      (FS), and T1-weighted FS postgadolinium sequences at baseline and at 6 months.
      Enthesitis and associated osteitis were scored semiquantitatively in pre- and
      posttreatment scans. RESULTS: There was a statistically significant improvement
      in all clinical and functional parameters (P = 0.008 for VAS spinal pain score
      during the day and for VAS spinal pain score during the night, P = 0.008 for the
      BASFI, and P = 0.005 for the BASDAI) as well as in quality of life (P = 0.005 for
      the ASQoL) at 6 months. Nine patients had a total of 44 MRI-detectable entheseal
      lesions. These were seen in the SI joints in 6 patients (n = 15 lesions), in the
      lumbar or cervical spine in 9 patients (n = 22 lesions), and in peripheral joints
      in 5 patients (n = 7 lesions). Overall, 86% of MRI-detected entheseal lesions
      either regressed completely or improved. No new lesions developed. CONCLUSION:
      These findings suggest that TNFalpha blockade with etanercept is markedly
      effective in controlling the clinical manifestations of SpA that is resistant to
      disease-modifying antirheumatic drugs. This is associated with marked improvement
      of enthesitis and associated osteitis pathology as determined by MRI.

PMID- 11592376
TI  - Influence of HLA-DR phenotype on the risk of hepatitis C virus-associated mixed
      cryoglobulinemia.
AB  - OBJECTIVE: Circumstances predisposing hepatitis C virus (HCV)-infected patients
      to develop mixed cryoglobulinemia (MC), which may manifest as a small-vessel
      systemic vasculitis (MC vasculitis), remain unclear. Previous studies have failed
      to demonstrate a clear role of either viral factors (genotype, viral load) or
      host factors (lymphocytes or immunoglobulin subsets). This study was undertaken
      to examine a possible role of HLA class II alleles in HCV-associated MC. METHODS:
      One hundred fifty-eight HCV-infected patients, of whom 76 had MC (56 with type II
      MC and 20 with type III MC) and 82 did not have MC, were studied prospectively.
      MC vasculitis was noted in 35 HCV-infected patients with type II IgMkappa
      containing cryoglobulins. HLA-DRB1 and HLA-DQB1 polymorphism was analyzed by
      hybridization using allele-specific oligonucleotides, after gene amplification.
      The odds ratio (OR) was calculated with Woolf's method. Then, using multivariate
      analysis, demographic, biologic, immunologic, virologic, and liver histologic
      factors associated with the presence of MC and MC vasculitis were investigated.
      RESULTS: HLA-DR11 was significantly more frequent in patients with type II MC
      than in those without MC (41.1% versus 17.1%; OR 3.4, corrected P [Pcorr] =
      0.017), regardless of the presence of vasculitis accompanying the MC (37.1% of
      those with MC vasculitis, 34.1% of those with MC but no vasculitis). HLA-DR7 was
      less frequent in HCV-infected patients with MC than in those without MC (13.2%
      versus 30.5%; OR 0.34, P = 0.012, Pcorr not significant), with a particularly
      lower frequency in those with type II MC and those with MC vasculitis (12.5% and
      8.6%, respectively). There was no significant difference in HLA-DQB1 distribution
      between the different patient groups. By univariate and multivariate analysis,
      HLA-DR11 was the only positive predictive factor, besides female sex and advanced
      age, for the presence of MC and HCV-associated MC vasculitis (OR 2.58).
      CONCLUSION: Our results indicate that the presence of the DR11 phenotype is
      associated with a significantly increased risk for the development of type II MC
      in patients with chronic HCV infection. In contrast, HLA-DR7 appears to protect
      against the production of type II MC. These results suggest that the host's
      immune response genes may play a role in the pathogenesis of HCV-associated MC.

PMID- 11592377
TI  - Cognitive function in fibromyalgia patients.
AB  - OBJECTIVE: To evaluate fibromyalgia (FM) patients for the presence of cognitive
      deficits and to test the hypothesis that abnormalities would fit a model of
      cognitive aging. METHODS: We studied 3 groups of patients: FM patients without
      concomitant depression and in the absence of medications known to affect
      cognitive function (n = 23), age- and education-matched controls (n = 23), and
      education-matched older controls who were individually matched to be 20 years
      older (+/- 3 years) than the FM patients (n = 22). We measured speed of
      information processing, working memory function, free recall, recognition memory,
      verbal fluency, and vocabulary. We correlated performance on cognitive tasks with
      FM symptoms, including depression, anxiety, pain, and fatigue. We also determined
      if memory complaints were correlated with cognitive performance. RESULTS: As
      expected, older controls performed more poorly than younger controls on speed of
      processing, working memory, free recall, and verbal fluency. FM patients
      performed more poorly than age-matched controls on all measures, with the
      exception of processing speed. FM patients performed much like older controls,
      except that they showed better speed of processing and poorer vocabulary.
      Impaired cognitive performance in FM patients correlated with pain complaints,
      but not with depressive or anxiety symptoms. FM patients reported more memory
      problems than did the older and younger controls, and these complaints correlated
      with poor cognitive performance. CONCLUSION: Cognitive impairment in FM patients,
      particularly memory and vocabulary deficits, are documented in the study.
      Nevertheless, the intact performance on measures of information processing speed
      suggests that the cognitive deficits are not global. FM patients' complaints
      about their memory are likely to be legitimate, since their memory function is
      not age appropriate.

PMID- 11592378
TI  - Hemarthrosis: an unusual complication of type 1 neurofibromatosis.
AB  - Type 1 neurofibromatosis is one of the most common autosomal-dominant disorders
      and often includes orthopedic manifestations. We report the case of a 48-year-old
      woman with hemarthrosis caused by a popliteal cyst infiltrated by a diffuse
      neurofibroma associated with angiodysplasia. Surgical resection of this tumor was
      followed by postoperative hemorrhagic complications.

PMID- 11592379
TI  - Prospective evaluation of magnetic resonance imaging and physical examination
      findings in patients with greater trochanteric pain syndrome.
AB  - OBJECTIVE: This study examined patients with greater trochanteric pain syndrome
      (GTPS) to determine the prevalence of gluteus medius pathology by utilizing
      magnetic resonance imaging (MRI), and to evaluate the presence of Trendelenburg's
      sign, pain on resisted hip abduction, and pain on resisted hip internal rotation
      as predictors of a gluteus medius tear in this group of patients. METHODS: Twenty
      four subjects with clinical features consistent with GTPS were recruited. A
      standard physical assessment was performed at study entry, including assessment
      of the 3 specific physical signs. Following this initial assessment, MRI of the
      affected hip was performed. A 1.5T whole body MRI system was utilized, with T1
      and T2 fast spin-echo sequences performed in the coronal and axial planes. All MR
      images were reviewed in random order by a single radiologist. In 12 patients, the
      3 physical signs were assessed at study entry and at 2 months by the same
      observer and the intraobserver reliability for each of the signs was calculated.
      RESULTS: All subjects were women (median age 58 years, range 36-75 years). The
      median duration of symptoms was 12 months (range 12-60 months). MRI findings were
      as follows: 11 patients (45.8%) had a gluteus medius tear, 15 patients (62.5%)
      had gluteus medius tendinitis (pure tendinitis in 9 patients and tendinitis with
      a tear in 6 patients), 2 patients had trochanteric bursal distension, and 1
      patient had avascular necrosis of the femoral head. Trendelenburg's sign was the
      most accurate of the 3 physical signs in predicting a tendon tear, with a
      sensitivity of 72.7% and a specificity of 76.9%. Moreover, Trendelenburg's sign
      was the most reliable measure, with a calculated intraobserver kappa of 0.676
      (95% confidence interval 0.270-1.08). CONCLUSION: The results support the
      hypothesis that gluteus medius tendon pathology is important in defining GTPS. In
      this series, trochanteric bursal distension was uncommon and did not occur in the
      absence of gluteus medius pathology. The physical findings suggest that
      Trendelenburg's sign is the most sensitive and specific physical sign for the
      detection of gluteus medius tears, with an acceptable intraobserver reliability.
      Further delineation with MRI, especially in patients with a positive
      Trendelenburg's sign, is recommended prior to any consideration of surgery in
      this group of patients. Finally, with the pathology of this condition defined,
      the challenge will be to devise and assess, by randomized controlled trial, an
      appropriate treatment strategy for this group of patients.

PMID- 11592380
TI  - Defective Fas ligand-mediated apoptosis predisposes to development of a chronic
      erosive arthritis subsequent to Mycoplasma pulmonis infection.
AB  - OBJECTIVE: To determine whether defective T cell apoptosis is associated with the
      development of a chronic arthritis subsequent to mycoplasma infection, and to
      determine whether deletion of T cells can prevent the development of this
      arthritis. METHODS: B6 wild-type (B6-+/+), B6-lpr/lpr, and B6-gld/gld mice were
      infected with Mycoplasma pulmonis. The severity of lymphocytic infiltration and
      joint damage was evaluated, and the degree of recovery of viable mycoplasma from
      the spleen and joints was determined. Antigen-presenting cells derived from Fas
      mutant lpr mice (lpr-APC) were transfected ex vivo with an adenovirus (Ad) vector
      to yield lpr-APC expressing high levels of Fas ligand (lpr-APC-AdFasL), which in
      turn were transferred intraperitoneally into M pulmonis-infected B6-gld/gld mice.
      The development of arthritis subsequent to M pulmonis infection and the induction
      of apoptosis of cells within the synovial tissue and lymph nodes of lpr-APC
      AdFasL-treated B6-gld/gld mice were determined. RESULTS: Infection of B6-lpr/lpr
      and B6-gld/gld mice with M pulmonis resulted in an acute-phase inflammation of
      the synovium that later developed into a chronic erosive arthritis. Similar
      infection of B6-+/+ mice resulted only in an acute joint inflammatory response
      that resolved. Chronic arthritis in B6-gld/gld mice and B6-lpr/lpr was not due to
      persistent infection, since there were no differences in the rates of clearance
      of M pulmonis from the joints of B6-gld/gld or B6-lpr/lpr mice compared with B6
      +/+ mice. Treatment of infected B6-gld/gld mice with lpr-APC-AdFasL resulted in a
      significantly decreased incidence of chronic arthritis that was associated with a
      decrease in lymph node T cells, but not with apoptosis of synovial T cells or
      fibroblasts. CONCLUSION: Defective Fas/FasL-mediated apoptosis of T cells is an
      important factor that rendered arthritis-resistant B6 mice susceptible to the
      development of a chronic erosive arthritis subsequent to mycoplasma infection. In
      vivo lpr-APC-AdFasL cell-gene therapy is a safe and effective method for
      inhibiting the development of this arthritis.

PMID- 11592381
TI  - Treatment of murine collagen-induced arthritis by ex vivo extracellular
      superoxide dismutase gene transfer.
AB  - OBJECTIVE; Superoxide dismutase (SOD) is a potent antiinflammatory enzyme that
      has received growing attention for its therapeutic potential. This study was
      undertaken to examine the efficacy of extracellular SOD (EC-SOD) gene therapy in
      murine collagen-induced arthritis. METHODS: Embryonic DBA/1 mouse fibroblasts
      were infected with a recombinant retrovirus expressing human EC-SOD. DBA/1 mice
      that had been treated with type II collagen were administered subcutaneous
      injections of 2 x 10(7) EC-SOD-expressing fibroblasts on day 29, when symptoms of
      arthritis were already present. The severity of arthritis in individual mice was
      evaluated in a double-blind manner; each paw was assigned a separate clinical
      score, and hind paw thickness was measured with a caliper. Mice were killed on
      day 50 for histologic examination of the joints. RESULTS: High serum
      concentrations of EC-SOD were maintained for at least 7 days. Mice treated with
      the transgene exhibited significant suppression of clinical symptoms such as
      disabling joint swelling, deformity, and hind paw thickness, compared with the
      untreated group (mean +/- SD maximum clinical score in the untreated and the
      transgene-treated groups 2.71 +/- 1.08 and 1.35 +/- 1.22, respectively; P < 0.01,
      and hind paw thickness 3.04 +/- 0.18 mm and 2.56 +/- 0.12 mm, respectively; P <
      0.05). Histologic abnormalities, including destruction of cartilage and bone,
      infiltration of mononuclear cells, and proliferation of synovial cells, were also
      markedly improved in the EC-SOD-treated mice compared with the control group
      (histopathologic score 7.50 +/- 1.13 and 4.13 +/- 1.88 in the untreated and
      transgene-treated groups, respectively; P < 0.05). CONCLUSION: These results
      indicate that EC-SOD gene transfer may be an effective form of therapy for
      rheumatoid arthritis.

PMID- 11592382
TI  - Enhancement of collagen-induced arthritis in female mice by estrogen receptor
      blockage.
AB  - OBJECTIVE: To determine whether estrogen-mediated suppression of collagen-induced
      arthritis (CIA) in mice acts via the nuclear estrogen receptors (ERs). METHODS:
      CIA was induced in noncastrated normal (B10.Q x DBA/1)F1 (QD) female mice. The
      mice were treated with the ER antagonist ICI 182,780, which binds to both ERalpha
      and ERbeta, either on days 2, 6, 10, and 14 or on days 14, 18, 22, and 26 after
      type II collagen (CII) immunization. The effects of treatment and development of
      arthritis were correlated with the estrus cycle by inspection of vaginal smears
      (VS). By a combination of treatments with both estriol (E3) and ICI 182,780
      during the time of expected onset of CIA in castrated QD female mice, the
      protective effect of E3 in CIA was analyzed. RESULTS: Treatment with ICI 182,780
      of QD female mice immunized with CII triggered an earlier onset of arthritis
      during the period when the estrus cycle was blocked. The arthritis-modulating
      effect of ICI 182,780 was even obtained at doses that were insufficient to block
      estrus cycling, as observed in the VS response. E3 is an estrogen with low
      estrogenic potency but with a relatively potent antiarthritis effect. Doses of
      ICI 182,780 that were suboptimal for blocking estrus cycling blocked the E3
      mediated suppression of CIA in castrated female mice. CONCLUSION: These findings
      show that estrogen-induced suppression of CIA is mediated via the nuclear ERs and
      is operating at physiologic, possibly even subphysiologic, levels of estrogens.

PMID- 11592383
TI  - Interleukin-17 enhances tumor necrosis factor alpha-induced synthesis of
      interleukins 1,6, and 8 in skin and synovial fibroblasts: a possible role as a
      "fine-tuning cytokine" in inflammation processes.
AB  - OBJECTIVE: To compare the singular and combined effects of tumor necrosis factor
      alpha (TNFalpha), interleukin-1beta (IL-1beta), and IL-17 on messenger RNA (mRNA)
      expression, translation, and secretion of IL-6, IL-8, and IL-1beta in
      fibroblasts. METHODS: Fibroblasts were stimulated with the relevant cytokine(s),
      pulse labeled with 35S-methionine, and the newly synthesized proteins were
      immunoprecipitated and subjected to sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Gene expression was determined by Northern blot analysis.
      Secreted proteins were detected by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: IL-17 alone was a weaker stimulator of the transcription, translation,
      and secretion of other interleukins than was TNFalpha or IL-1beta. IL-17 (10
      ng/ml) stimulated the expression of IL-6 mRNA by 1.3-fold, while TNFalpha (1
      ng/ml) increased it by 3.7-fold, and IL-1beta (0.1 ng/ml) increased it by >30
      fold. Unlike TNFalpha and IL-1beta, IL-17 hardly affected the expression of IL-8
      and IL-1beta mRNA. Translation of IL-6 was 6.2 times greater with IL-17, but
      TNFalpha and IL-1beta stimulated it 28.9- and 174-fold, respectively. ELISA
      measured secretion of IL-6 and IL-8 increased by 6.7 and 5.8 times, respectively,
      with IL-17, compared with 52 and 269 times with TNFalpha stimulation and 1,356
      and 1,084 times with IL-1beta stimulation. Yet, when IL-17 was combined with
      other cytokines, these activities were stimulated much beyond the sum of the
      individual effects. The combination of IL-17 and TNFalpha induced the expression
      of IL-6 or IL-1beta mRNA 7 times more than their additive stimulation, and that
      of IL-8 mRNA 3.8 times more. Likewise, the secretion of IL-6 and IL-8 was 20
      times and 5 times higher, respectively, than expected. This synergism started
      after 4 hours of combined treatment, and decayed after 24-48 hours regardless of
      cytokine presence. It could be blocked with anti-IL-17 but not with anti-IL-1.
      CONCLUSION: Our findings suggest that the primary role of IL-17 is to synergize
      with TNFalpha and to fine-tune the inflammation process. Therefore, IL-17 may be
      a potential target for therapeutic intervention.

PMID- 11592384
TI  - Inhibition of bone resorption in vitro and prevention of ovariectomy-induced bone
      loss in vivo by flurbiprofen nitroxybutylester (HCT1026).
AB  - OBJECTIVE: Inhibitors of prostaglandin production, such as nonsteroidal
      antiinflammatory drugs (NSAIDs), and pharmacologic nitric oxide (NO) donors, such
      as organic nitrates, have been suggested to protect against bone loss in both
      humans and experimental animals. Recently, a new class of nitrosylated NSAID
      (known as NO-NSAIDs) has been developed, which combines the properties of a NO
      donor with those of a cyclooxygenase (COX) inhibitor. This study investigated the
      effects of one of these compounds, flurbiprofen nitroxybutylester (HCT1026), on
      bone metabolism in vitro and in vivo. METHODS: The effects of HCT1026 on
      osteoclast formation and resorption were determined in vitro using cocultures of
      primary mouse osteoblasts and osteoclasts. The effect of HCT1026 in vivo was
      assessed using a mouse model of ovariectomy-induced bone loss. RESULTS: HCT1026
      was significantly more efficacious than the parent compound, flurbiprofen, at
      inhibiting osteoclast formation and bone resorption in vitro, and these effects
      could not be reproduced by combinations of flurbiprofen with a variety of NO
      donors. Studies in vivo showed that HCT1026 protected against ovariectomy-induced
      bone loss by inhibiting osteoclastic bone resorption, whereas flurbiprofen at
      similar concentrations was ineffective. CONCLUSION: These data indicate that
      HCT1026 is a potent inhibitor of bone resorption in vitro and protects against
      ovariectomy-induced bone loss in vivo by a novel mechanism that appears to be
      distinct from its NO donor properties and from its inhibitory effects on COX
      activity. We conclude that HCT1026 may be of clinical value in the prevention and
      treatment of inflammatory diseases such as rheumatoid arthritis, which are
      characterized by joint inflammation as well as periarticular and systemic bone
      loss.

PMID- 11592385
TI  - Triptolide, a novel diterpenoid triepoxide from Tripterygium wilfordii Hook. f.,
      suppresses the production and gene expression of pro-matrix metalloproteinases 1
      and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in
      human synovial fibroblasts.
AB  - OBJECTIVE: Various extracts of the Chinese herbal remedy Tripterygium wilfordii
      Hook. f. (TWHF) have been reported to be therapeutically efficacious in
      rheumatoid arthritis (RA) in China, but their mechanism of action remains
      unclear. We investigated the effect of triptolide, a diterpenoid triepoxide from
      TWHF, on the production of pro-matrix metalloproteinase 1 (proMMP-1; or
      procollagenase 1 or pro-interstitial collagenase 1), proMMP-3 (or prostromelysin
      1), tissue inhibitors of metalloproteinases (TIMPs), and proinflammatory
      cytokines in human synovial fibroblasts and J774A.1 mouse macrophages. METHODS:
      Human synovial fibroblasts and mouse macrophages were cultured with interleukin
      1alpha (IL-1alpha) or lipopolysaccharide (LPS) in the presence or absence of
      triptolide. The production of proMMPs 1 and 3, TIMPs 1 and 2, cyclooxygenase 1
      (COX-1) and COX-2, prostaglandin E2 (PGE2), IL-1beta, and IL-6 was assayed by
      Western blot analysis and enzyme-linked immunosorbent assay. Gene expression of
      proMMPs 1 and 3, TIMPs 1 and 2, COX-1 and COX-2, IL-1alpha, IL-1beta, tumor
      necrosis factor alpha (TNFalpha), and IL-6 was also monitored by Northern blot
      analysis and reverse transcriptase-polymerase chain reaction. RESULTS: Triptolide
      suppressed the IL-1alpha-induced production of proMMPs 1 and 3 and decreased
      their messenger RNA levels in human synovial fibroblasts. In contrast, the IL
      1alpha-induced gene expression and production of TIMPs 1 and 2 were further
      augmented by triptolide in the synovial cells. Triptolide also inhibited the IL
      1alpha-induced production of PGE2 by selectively suppressing the gene expression
      and production of COX-2, but not those of COX-1. In addition, triptolide
      suppressed the LPS-induced production of PGE2 in mouse macrophages. Furthermore,
      the gene expression of IL-1alpha, IL-1beta, TNFalpha, and IL-6, as well as the
      production of IL-1beta and IL-6, were inhibited by triptolide in the LPS-treated
      mouse macrophages. CONCLUSION: We have demonstrated for the first time that the
      therapeutic effects of TWHF in RA are due in part to the novel chondroprotective
      effect of triptolide via the direct suppression of the production of proMMPs 1
      and 3 and the simultaneous up-regulation of TIMPs in IL-1-treated synovial
      fibroblasts. Triptolide's interference with gene expression of proinflammatory
      cytokines and its known inhibitory effects on PGE2 production are also probably
      very effective.

PMID- 11592386
TI  - The molecular mechanism of action of the antiresorptive and antiinflammatory drug
      clodronate: evidence for the formation in vivo of a metabolite that inhibits bone
      resorption and causes osteoclast and macrophage apoptosis.
AB  - OBJECTIVE: The primary aims of this study were to determine whether clodronate
      and liposome-encapsulated clodronate are metabolized to adenosine 5'-(beta,gamma
      dichloromethylene) triphosphate (AppCCl2p) by osteoclasts and macrophages in
      vivo, and to determine whether intracellular accumulation of this metabolite
      accounts for the antiresorptive and antimacrophage effects of clodronate. To
      compare the mechanism of action of clodronate and alendronate, effects on protein
      prenylation in osteoclasts and macrophages in vivo were also assessed. METHODS:
      High-performance liquid chroma-tography-mass spectrometry was used to determine
      whether rabbit osteoclasts (purified ex vivo with immunomagnetic beads)
      metabolize clodronate, and whether rat peritoneal macrophages metabolize liposome
      encapsulated clodronate, following in vivo administration. The effects of
      clodronate and AppCCl2p on bone resorption, osteoclast number, and apoptosis in
      vitro were compared. Using an antibody to the unprenylated form of RaplA, effects
      on protein prenylation were assessed by Western blot analysis of osteoclast and
      peritoneal macrophage lysates from bisphosphonate-treated animals. RESULTS:
      AppCCl2p could be detected in extracts from osteoclasts purified from clodronate
      treated rabbits. Intracellular accumulation of AppCCl2p caused a reduction in the
      number of osteoclasts, increased osteoclast apoptosis, and inhibited bone
      resorption in vitro. These effects were indistinguishable from those of
      clodronate. Liposome-encapsulated clodronate was also metabolized to AppCCl2p by
      rat peritoneal macrophages in vivo. Liposome-encapsulated clodronate caused an
      increase in peritoneal macrophage apoptosis in ex vivo cultures that was
      indistinguishable from the increase in apoptosis caused by liposome-encapsulated
      AppCCl2p. Unlike alendronate, clodronate and its metabolite did not affect
      prenylation of the small GTPase RaplA in osteoclasts or macrophages in vivo.
      CONCLUSION: These results provide the first direct evidence that the
      antiinflammatory and antiresorptive effects of clodronate on macrophages and
      osteoclasts in vivo occur via the intracellular formation of AppCCl2p.

PMID- 11592387
TI  - Monocyte chemoattractant protein 1 gene regulatory region polymorphism and serum
      levels of monocyte chemoattractant protein 1 in Japanese patients with Kawasaki
      disease.

PMID- 11592388
TI  - Detection of the single-base substitution -174 G-->C in the interleukin-6 gene by
      real-time polymerase chain reaction: comment on the article by Moos et al.

PMID- 11592389
TI  - Roger D. Kornberg--Felix Hoppe-Seyler Lecture 2001.

PMID- 11592390
TI  - The eukaryotic gene transcription machinery.
AB  - Seven purified proteins may be combined to reconstitute regulated, promoter
      dependent RNA polymerase II transcription: five general transcription factors,
      Mediator, and RNA polymerase II. The entire system has been conserved across
      species from yeast to humans. The structure of RNA polymerase II, consisting of
      10 polypeptides with a mass of about 500 kDa, has been determined at atomic
      resolution. On the basis of this structure, that of an actively transcribing RNA
      polymerase II complex has been determined as well.

PMID- 11592391
TI  - Paper of the year 2000: award to Eva Estebanez-Perpina and Pablo Fuentes-Prior.

PMID- 11592392
TI  - GABA(C) receptors: a molecular view.
AB  - In the central nervous system inhibitory neurotransmission is primarily achieved
      through activation of receptors for gamma-aminobutyric acid (GABA). Three types
      of GABA receptors have been identified on the basis of their pharmacological and
      electrophysiological properties. The predominant type, termed GABA(A), and a
      recently identified GABA(C) type, form ligand-gated chloride channels, whereas
      GABA(B) receptors activate separate cation channels via G proteins. Based on
      their homology to nicotinic acetylcholine receptors, GABA(C) receptors are
      believed to be oligomeric protein complexes composed of five subunits in a
      pentameric arrangement. To date up to five different GABA(C) receptors subunits
      have been identified in various species. Recent studies have shed new light on
      the biological characteristics of GABA(C) receptors, including the chromosomal
      localization of its subunit genes and resulting links to deseases, the cloning of
      new splice variants, the identification of GABA(C) receptor-associated proteins,
      the identification of domains involved in subunit assembly, and finally
      structure/function studies examining functional consequences of introduced
      mutations. This review summarizes recent data in view of the molecular structure
      of GABA(C) receptors and presents new insights into the biological function of
      this protein in the retina.

PMID- 11592393
TI  - Recent advances in plant MAP kinase signalling.
AB  - Mitogen activated protein kinases (MAPK) are important mediators in signal
      transmission, connecting the perception of external stimuli to cellular
      responses. MAPK cascades are involved in signalling various biotic and abiotic
      stresses, like wounding and pathogen infection, temperature stress or drought,
      but are also involved in mediating the action of some plant hormones, such as
      ethylene and auxin. Moreover, MAPKs have been implicated in cell cycle and
      developmental processes. In Arabidopsis mutant screens and in vivo assays several
      components of plant MAPK cascades have been identified. This review gives an
      update of recent advances in plant MAPK signalling and discusses the emerging
      mechanisms of some selected MAPK pathways.

PMID- 11592394
TI  - The chemical biology of Ras lipidation.
AB  - In this review, we summarize the successful interplay between three disciplines,
      organic synthesis, biophysics and cell biology, in the study of protein
      lipidation and its relevance to targeting of proteins to the plasma membrane of
      cells in molecular detail. Highlighting the example of the Ras proteins, we show
      how the development of new synthetic methodologies paved the road to the
      synthesis of lipidated peptides and--by a combination of chemical and molecular
      biological techniques--lipidated proteins as molecular tools. We further give an
      overview of the results of the biophysical properties and biological activities
      of the molecules synthesized by means of this interdisciplinary approach. This
      successful combination of different disciplines led to a better understanding of
      the selective targeting of Ras and related lipoproteins to the plasma membrane.

PMID- 11592395
TI  - This is the end: processing, editing and repair at the tRNA 3'-terminus.
AB  - The generation of a mature tRNA 3'-end is an important step in the processing
      pathways leading to functional tRNA molecules. While 5'-end processing by RNase P
      is similar in all organisms, generation of the mature 3'-terminus seems to be
      more variable and complex. The first step in this reaction is the removal of 3'
      trailer sequences. In bacteria, this is a multistep process performed by endo-
      and exonucleases. In contrast, the majority of eukaryotes generate the mature
      tRNA 3'-end in a single step reaction, which consists of an endonucleolytic cut
      at the tRNA terminus. After removal of the 3'-trailer, a terminal CCA triplet has
      to be added to allow charging of the tRNA with its cognate amino acid. The enzyme
      catalyzing this reaction is tRNA nucleotidyltransferase, homologs of which have
      been found in representatives of all three kingdoms. Furthermore, in metazoan
      mitochondria, some genes encode 3'-terminally truncated tRNAs, which are restored
      in an editing reaction in order to yield functional tRNAs. Interestingly, this
      reaction is not restricted to distinct tRNAs, but seems to act on a variety of
      tRNA molecules and represents therefore a more general tRNA repair mechanism than
      a specialized editing reaction. In this review, the current knowledge about these
      crucial reactions is summarized.

PMID- 11592396
TI  - Binding of IRE-BP to its cognate RNA sequence: SFM studies on a universal RNA
      backbone for the analysis of RNA-protein interaction.
AB  - We have used an RNA consisting of the potato spindle tuber viroid (PSTVd) and 240
      bp of double-stranded RNA derived from the GUS gene as a backbone for scanning
      force microscope (SFM) studies on RNA binding proteins. The in vitro transcribed
      RNA forms a rod-like structure of apparent 130 nm in length with a completely
      base paired central part flanked by the incompletely paired viroid helix with
      bulges on both sides. The termini of the molecule consist of loops such that no
      blunt or staggered RNA ends are exposed. Suitable, asymmetrical restriction sites
      in the construct allow for the insertion of sequences of interest, e. g. protein
      binding sites. We have inserted the IRE (iron responsive element) sequence into
      the construct and have used in vitro transcripts to study binding of IRE-BP.
      Relative binding frequencies show that 70% of the protein binds to the expected
      site in the molecule while only a slightly enhanced binding is observed at the
      termini. In the GUS-PSTVd-IRE backbone, the orientation of the molecule is easily
      determined by IRE-BP binding. It thus provides a versatile tool to study specific
      as well as preferential interaction of other proteins with sequences or
      structures inserted into a different part of the molecule.

PMID- 11592397
TI  - PAF67, a novel protein that is associated with the initiation-competent form of
      RNA polymerase I.
AB  - Mammalian RNA polymerase I (Pol I) is a multisubunit enzyme that is decorated
      with accessory proteins, termed PAFs (polymerase-associated factors). The
      presence or absence of distinct PAFs may account for the functional differences
      of distinct fractions of cellular Pol I, and suggests that PAFs could be targets
      of regulatory pathways. Here we describe and functionally characterize PAF67, a
      novel 67 kDa protein that is tightly associated with a subpopulation of cellular
      Pol I. Both PAF67-containing and -deficient Pol I transcribe non-specific
      templates with similar efficiency, however, only the enzyme that contains PAF67
      is capable of specifically transcribing rDNA templates. PAF67 co-localizes with
      Pol I in the nucleolus at sites of active rDNA transcription, indicating that
      PAF67 serves a role in rDNA transcription initiation. The results suggest that
      association of PAF67 with the 'core' enzyme endows Pol I with the capability to
      assemble into a productive transcription initiation complex at the rDNA promoter.

PMID- 11592398
TI  - Characterization of RNase P holoenzymes from Methanococcus jannaschii and
      Methanothermobacter thermoautotrophicus.
AB  - The partial purification and basic biochemical characterization of the RNase P
      holoenzymes of two species of methanogenic Archaea, Methanothermobacter
      thermoautotrophicus (previously Methanobacterium thermoautotrophicum strain
      deltaH) and Methanococcus jannaschii, are described. The properties of these
      enzymes, particularly buoyant density in Cs2SO4 and recent information about the
      subunit composition of the archaeal enzymes, suggest that RNase P enzymes in
      Archaea are much more alike than earlier studies in Sulfolobus acidocaldarius and
      Haloferax volcanii suggested.

PMID- 11592399
TI  - Identification of functional regions of guanylate cyclase-activating protein 1
      (GCAP1) using GCAP1/GCIP chimeras.
AB  - Guanylate cyclase-activating protein 1 (GCAP1) and guanylate cyclase-inhibitory
      protein (GCIP) are calmodulin-related Ca2+-binding proteins expressed in
      vertebrate photoreceptor cells. GCAP1 activates photoreceptor guanylate cyclase 1
      (GC1) at low free [Ca2+] (<50 nM, in the light), but inhibits it at physiological
      high [Ca2+] (1 microM, in the dark). GCIP, a Ca2+-binding protein from frog
      retina, inhibits GC1 at approximately 1 microM [Ca2+], but is unable to stimulate
      cyclase at low [Ca2+]. In this study, we probed the interaction between GCAP1 and
      GC1 by producing GCAP1/GCIP chimeras and tested their capability to stimulate
      GC1. We prepared eight pairs of constructs in which the N-terminal portions of
      GCIP and GCAP1 were successively replaced by corresponding domains of GCAP1, and
      GCIP, respectively. The expressed proteins were purified and tested for
      stimulation of GC1 at 50 nM [Ca2+], and their ability to competitively inhibit
      GC1 stimulation by a Ca2+-insensitive GCAP1 mutant, GCAP1-tm, at high [Ca2+].
      While all GCAP1/GCIP chimeras competitively inhibited GC1 stimulation at high
      [Ca2+] by GCAP1-tm, several of the GCIP/GCAP1 chimeras had no effect. A chimera
      consisting of residues 1-20 of GCIP and 21-205 of GCAP1 had no effect on GC1 at
      low [Ca2+], suggesting that the N-terminal region MGNIMDGKSVEELSSTECHQ, which has
      no sequence similarity to GCIP, is among the key components necessary for GC1
      stimulation. A GCAP1/GCIP chimera consisting of residues 1-43 (including
      nonfunctional EF1) of GCAP1 and residues 56-206 of GCIP stimulated GC1 at low
      [Ca2+] and inhibited GC1 at high [Ca2+], suggesting that the essential components
      required to transform an inhibitory to an activating protein are contained within
      the N-terminal region of GCAP1 (residues 1-43).

PMID- 11592400
TI  - Cooperativity of binding epitopes and receptor chains in the BMP/TGFbeta
      superfamily.
AB  - Bone morphogenetic proteins (BMP) are dimeric factors initiating several distinct
      signaling cascades by binding to two types of transmembrane serine/threonine
      kinase receptors (BRI and BRII), and are thus regulating several steps in
      embryonal development and adult tissue homeostasis. BMP-2 contains two
      symmetrical pairs of juxtaposed epitopes: the wrist epitope with high affinity to
      BRI consists of residues from both BMP-2 monomers, while the knuckle epitope
      resembles the low affinity site for BRII and comprises residues from only one
      monomer. Here we generated heterodimeric BMP-2 muteins with one monomer mutant in
      either epitope I for BRI (eI-) or epitope II for BRII (eII-) and the second
      monomer wild type for receptor interactions (m-). These muteins (B2eI-/B2m- and
      B2eII-/B2m-) were analyzed by biosensor analysis as well as by measuring their
      biological activity and compared to their homodimeric forms (either wild type or
      mutant). Depletion of only one epitope II results in the loss of biological
      activity as measured byalkaline phosphatase (ALP) activity and Smad induced
      reportergene assays. However, depletion of only one epitope I shows a reduction
      of ALP activity to about 25%, while the activation of the Smad pathway remained
      normal. Homomeric muteins are non-functional for both Smad and ALP activation.
      This suggests that two functional epitopes II have to be present on one BMP-2
      molecule for receptor activation. Futhermore, both pathways (Smad and ALP) are
      triggered differently by distinct BMP-receptor complexes. Heteromeric BMP-2
      mutants therefore allow a distinguishable manipulation of either pathway and thus
      represent important tools for the generation of specific BMP-2 antagonists or
      agonists.

PMID- 11592402
TI  - Functional expression and characterization of odorant receptors using the Semliki
      Forest virus system.
AB  - The human olfactory system can recognize and discriminate a large number of
      different odorant molecules. The detection of chemically distinct odorants starts
      with the binding of an odorant ligand to a specific receptor protein on the
      olfactory neuron cell surface. To address the problem of olfactory perception at
      a molecular level, we have expressed and characterized different olfactory
      receptors with several expression systems. Here we provide the first
      documentation of functional expression of odorant receptors using the Semliki
      Forest virus system. The human odorant OR 17-40 receptor and the rat 17 receptor
      were functionally expressed in vertebrate kidney cells (HEK293) using recombinant
      Semliki Forest viruses. Receptors were expressed as a fusion protein with the N
      terminal membrane import sequence of the guinea pig serotonin receptor.
      Experiments employing the Ca2+-sensitive dye fura-2 revealed a fast, transient
      increase in the [Ca2+]i after application of the specific agonists helional and
      octanal to HEK293 cells infected with viruses containing RNA for the human
      odorant OR 17-40 receptor and the rat 17 receptor, respectively.

PMID- 11592401
TI  - Cyclo19,31[D-Cys19]-uPA19-31 is a potent competitive antagonist of the
      interaction of urokinase-type plasminogen activator with its receptor (CD87).
AB  - Urokinase-type plasminogen activator (uPA) represents a central molecule in
      pericellular proteolysis and is implicated in a variety of physiological and
      pathophysiological processes such as tissue remodelling, wound healing, tumor
      invasion, and metastasis. uPA binds with high affinity to a specific cell surface
      receptor, uPAR (CD87), via a well defined sequence within the N-terminal region
      of uPA (uPA19-31). This interaction directs the proteolytic activity of uPA to
      the cell surface which represents an important step in tumor cell proliferation,
      invasion, and metastasis. Due to its fundamental role in these processes, the
      uPA/uPAR-system has emerged as a novel target for tumor therapy. Previously, we
      have identified a synthetic, cyclic, uPA-derived peptide, cyclo19,31uPA19-31, as
      a lead structure for the development of low molecular weight uPA-analogues,
      capable of blocking uPA/uPAR-interaction [Burgle et al., Biol. Chem. 378 (1997),
      231-237]. We now searched for peptide variants of cyclo19,31uPA19-31 with
      elevated affinities for uPAR binding. Among other tasks, we performed a
      systematic D-amino acid scan of uPA19-31, in which each of the 13 L-amino acids
      was individually substituted by the corresponding D-amino acid. This led to the
      identification of cyclo19,31[D-Cys19]-uPA19-31 as a potent inhibitor of uPA/uPAR
      interaction, displaying only a 20 to 40-fold lower binding capacity as compared
      to the naturally occurring uPAR-ligands uPA and its amino-terminal fragment.
      Cyclo19,31[D-Cys19]-uPA19-31 not only blocks binding of uPA to uPAR but is also
      capable of efficiently displacing uPAR-bound uPA from the cell surface and to
      inhibit uPA-mediated, tumor cell-associated plasminogen activation and fibrin
      degradation. Thus, cyclo19,31[D-Cys19]-uPA19-31 represents a promising
      therapeutic agent to significantly affect the tumor-associated uPA/uPAR-system.

PMID- 11592403
TI  - Biophysical characterization of lipopolysaccharide and lipid A inactivation by
      lactoferrin.
AB  - The interaction of bacterial endotoxins (LPS Re and lipid A, the 'endotoxic
      principle' of LPS) with the endogenous antibiotic lactoferrin (LF) was
      investigated using various physical techniques and biological assays. By applying
      Fourier-transform infrared (FTIR) spectroscopy, we find that LF binds to the
      phosphate group within the lipid A part and induces a rigidification of the acyl
      chains of LPS. The secondary structure of the protein - as monitored by the amide
      I band - is, however, not changed. Concomitant with the IR data, scanning
      calorimetric data indicate a sharpening of the acyl chain phase transition. From
      titration calorimetric and zeta potential data, saturation of LF binding to LPS
      was found to lie at a [LF]:[LPS] ratio of 1:3 to 1:5 M from the former and 1:10 M
      from the latter technique. X-ray scattering data indicate a change of the lipid A
      aggregate structure from inverted cubic to multilamellar, and with fluorescence
      (FRET) spectroscopy, LF is shown to intercalate by itself into phospholipid
      liposomes and may also block the lipopolysaccharide-binding protein (LBP)-induced
      intercalation of LPS. The LPS-induced cytokine production of human mononuclear
      cells exhibits a decrease due to LF binding, whereas the coagulation of amebocyte
      lysate in the Limulus test exhibited concentration-dependent changes. Based on
      these results, a model for the mechanisms of endotoxin inactivation by LF is
      proposed.

PMID- 11592404
TI  - Zinc induces apoptosis that can be suppressed by lanthanum in C6 rat glioma
      cells.
AB  - Zinc ions have both essential and toxic effects on mammalian cells. Here we
      report the ability of zinc to act as an inducer of apoptosis in C6 rat glioma
      cells. Incubation with 150 to 300 microM ZnCl2 caused cell death that was
      characterized as apoptotic by internucleosomal DNA fragmentation, formation of
      apoptotic bodies, nuclear fragmentation and breakdown of the mitochondrial
      membrane potential. On the other hand, zinc deprivation by the membrane permeable
      chelator TPEN [N,N,N',N',-tetrakis (2-pyridyl-methyl)-ethylenediamine] also
      induced programmed death in this cell line, indicating the existence of
      intracellular zinc levels below and above which apoptosis is induced. Zinc
      induced apoptosis in C6 cells was independent of major signaling pathways
      (protein kinase C, mitogen activated protein kinase and guanylate cyclase) and
      protein synthesis, but was increased by facilitating zinc uptake with the
      ionophore pyrithione. Lanthanum(III)chloride was also able to increase the net
      zinc uptake, but nevertheless apoptotic features and zinc toxicity were reduced.
      Remarkably, lanthanum suppressed the zinc-induced breakdown of the mitochondrial
      membrane potential. We conclude that in C6 cells lanthanum acts in two different
      ways, as a promoter of net zinc uptake and as a suppressor of zinc-induced
      apoptosis.

PMID- 11592405
TI  - Functional dissection of trigger factor and DnaK: interactions with nascent
      polypeptides and thermally denatured proteins.
AB  - In Escherichia coli, the ribosome-associated Trigger Factor (TF) cooperates with
      the DnaK system in the folding of newly synthesized cytosolic polypeptides. Here
      we investigated the functional relationship of TF and DnaK by comparing various
      functional properties of both chaperones. First, we analyzed the ability of TF
      and DnaK to associate with nascent polypeptides and full-length proteins released
      from the ribosome. Toward this end, we established an E. coli based
      transcription/translation system containing physiological ratios of TF, DnaK and
      ribosomes. In this system, TF can be crosslinked to nascent polypeptides of
      sigma32. No TF crosslink was found to full-length sigma32, which is known to be a
      DnaK substrate. In contrast, DnaK crosslinked to both nascent and full-length
      sigma32. DnaK crosslinks critically depended on the type of chemical crosslinker.
      Crosslinks represent specific substrate-chaperone interactions since they relied
      on the association of the nascent polypeptides with the substrate binding pocket
      of DnaK. While DnaK is known to be the major chaperone to prevent protein
      aggregation under heat shock conditions, we found that TF did not prevent
      aggregation of thermally unfolded proteins in vitro and was not able to
      complement the heat-sensitive phenotype of a deltadnaK52 mutant in vivo. These
      data indicate that TF and DnaK show strong differences in their ability to
      prevent aggregation of denatured proteins and to associate with native like
      substrates, but share the ability to associate with nascent polypeptides.

PMID- 11592406
TI  - A persulfurated cysteine promotes active site reactivity in Azotobacter
      vinelandii Rhodanese.
AB  - Active site reactivity and specificity of RhdA, a thiosulfate:cyanide
      sulfurtransferase (rhodanese) from Azotobacter vinelandii, have been investigated
      through ligand binding, site-directed mutagenesis, and X-ray crystallographic
      techniques, in a combined approach. In native RhdA the active site Cys230 is
      found persulfurated; fluorescence and sulfurtransferase activity measurements
      show that phosphate anions interact with Cys230 persulfide sulfur atom and
      modulate activity. Crystallographic analyses confirm that phosphate and
      hypophosphite anions react with native RhdA, removing the persulfide sulfur atom
      from the active site pocket. Considering that RhdA and the catalytic subunit of
      Cdc25 phosphatases share a common three-dimensional fold as well as active site
      Cys (catalytic) and Arg residues, two RhdA mutants carrying a single amino acid
      insertion at the active site loop were designed and their phosphatase activity
      tested. The crystallographic and functional results reported here show that
      specific sulfurtransferase or phosphatase activities are strictly related to
      precise tailoring of the catalytic loop structure in RhdA and Cdc25 phosphatase,
      respectively.

PMID- 11592407
TI  - The catechol 1,2 dioxygenase system of Acinetobacter radioresistens: isoenzymes,
      inductors and gene localisation.
AB  - Two different isozymes (Iso A and Iso B) of catechol 1,2 dioxygenase (C1,2O) were
      isolated from cultures of A. radioresistens grown in two different media,
      containing phenol and benzoate respectively. In the phenol medium the bacteria
      expressed about 90% of Iso A, whereas in the benzoate medium the Iso A/Iso B
      ratio was 40:60. The two proteins have different molecular masses, isoelectric
      points and N-terminal sequences that are not consistent with simple post
      translational modifications. Furthermore, their behaviour differs at high
      temperatures (42 degrees C-47 degrees C) and at moderately acidic pH (pH 6.0):
      Iso A proved to be the more stable under conditions of environmental stress.
      Hybridisation analysis with an A. calcoaceticus catA-derived probe revealed that
      A. radioresistens C1,2O proteins are encoded by two chromosomally located genes.
      Bidimensional electrophoresis (2DE) maps of crude extracts of cells grown in
      different carbon sources (phenol, benzoate and acetate) clearly demonstrated a
      differential induction pattern for the two proteins. The hypothesis of a double
      set of genes, one for benzoate catabolism and the other for phenol catabolism, is
      discussed, and analogies are drawn with other known C1,2Os.

PMID- 11592408
TI  - A structural role for Asp83 in the photoactivation of rhodopsin.
AB  - Asp83 is a highly conserved residue in the second transmembrane domain of visual
      pigments and many members of other G protein-coupled receptor subfamilies. Upon
      illumination, the rod visual pigment rhodopsin proceeds through various
      intermediate states (Batho<-->BSI<-->Lumi<-->Meta I<-->Meta II). Meta II
      represents the active state of rhodopsin, which binds and activates the G protein
      transducin. Evidence has been presented that Asp83 participates in the formation
      of Meta II and undergoes a change in H-bonding. To investigate whether this role
      of Asp83 requires its proton-donating capacity and/or its H-bonding capability,
      we constructed the mutants D83C and D83N. Both mutants appear to effectively
      activate transducin, indicating that Asp83 is not essential for signal
      transduction. Differential effects of the mutations D83C and D83N are observed in
      the spectral properties and the pH sensitivity of the Meta I-->Meta II
      transition. In general, D83C behaves much more like wild-type than D83N. We
      conclude that the structural role of Asp83 also involves the acidic nature of its
      carboxyl group. In addition, the participation in Meta II formation of Cys83 in
      D83C manifests itself as a change in the vibrational properties of the sulfhydryl
      group, demonstrating that the -SH group can be used as a non-invasive probe for
      local structural changes.

PMID- 11592409
TI  - Photo-CIDNP 13C magic angle spinning NMR on bacterial reaction centres: exploring
      the electronic structure of the special pair and its surroundings.
AB  - Photochemically induced dynamic nuclear polarisation (photo-CIDNP) in intact
      bacterial reaction centres has been observed by 13C-solid state NMR under
      continuous illumination with white light. Strong intensity enhancement of 13C NMR
      signals of the aromatic rings allows probing the electronic ground state of the
      two BChl cofactors of the special pair at the molecular scale with atomic
      selectivity. Differences between the two BChl cofactors are discussed. Several
      aliphatic 13C atoms of cofactors, as well as 13C atoms of the imidazole ring of
      histidine residue(s), show nuclear-spin polarisation to the same extent as the
      aromatic nuclei of the cofactors. Mechanisms and applications of polarisation
      transfer are discussed.

PMID- 11592410
TI  - Pyrimidine-2,4,6-Triones: a new effective and selective class of matrix
      metalloproteinase inhibitors.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that have
      been implicated in various disease processes. Different classes of MMP
      inhibitors, including hydroxamic acids, phosphinic acids and thiols, have been
      previously described. Most of these mimic peptides and most likely bind in a
      similar way to the corresponding peptide substrates. Here we describe pyrimidine
      triones as a completely new class of metalloprotease inhibitors. While the
      pyrimidine-trione template is used as the zinc-chelating moiety, the substituents
      have been optimized to yield inhibitors comparable in their inhibition efficiency
      of matrix metalloproteinases to hydroxamic acid derivatives such as batimastat.
      However, they are much more specific for a small subgroup of MMPs, namely the
      gelatinases (MMP-2 and MMP-9).

PMID- 11592411
TI  - Effects of selected metal ions on photodegradation of organophosphorus pesticides
      sensitized by humic acids.
AB  - Selected metal ions having paramagnetic property were found to exert inhibition
      effects on aquatic photodegradation of organophosphorus pesticides sensitized by
      humic acids, according to the increasing order of Cr(III) < Co(II) < Mn(II) <
      Cu(II). Basic factors dominating the metal-ion effects were clarified on the
      basis of the fluorescence quenching as well as radical scavenging abilities of
      metal ions complexed with humic acids.

PMID- 11592412
TI  - Seasonal patterns of non-terpenoid C6-C10 VOC emission from seven Mediterranean
      woody species.
AB  - The seasonal pattern of non-terpenoid C6-C10 VOC emission by seven Mediterranean
      woody species (Bupleurum fruticosum, Cistus albidus, Pinus halepensis, Arbutus
      unedo, Erica arborea, Quercus coccifera, and Q. ilex) was studied under field
      conditions. Branch chamber samples were sorbed on carbotrap and analyzed by
      thermal desorption in combination with GC-MS. These non-terpenoid C6-C10 VOC
      emissions were large, almost of similar magnitude to those of terpenes. Overall,
      maximum values were recorded in spring and summer (up to 12 microg g(-1) DM h(-1)
      in Q. ilex) and minimum values in autumn and winter (up to 5 microg g(-1) DM h(
      1) in Q. ilex). These C6-C10 VOC emissions represented 2.82% of the
      photosynthetic C fixation in summer and 0.22% in winter. Some compounds such as 2
      ethoxyethyl acetate were emitted by most species, others such as 3-hexen-1-ol,
      phenol or decanal were significantly emitted only by few species. The greatest
      diversity of emitted non-terpenoid C6-C10 VOCs was observed in spring and in Q.
      ilex. Temperature seemed a strong driver of these seasonal changes but other
      species-specific and seasonal factors seem involved. These results indicate that
      C6-C10 non-terpenoid VOCs contribute a rather significant fraction of the total
      biogenic VOC flux from these Mediterranean species, especially in spring and
      summer, and therefore should be considered in VOC emission inventories and in
      model predictions of tropospheric chemistry.

PMID- 11592413
TI  - The occurrence of xenoestrogens in the Elbe river and the North Sea.
AB  - The xenoestrogens Bisphenol A (BPA), p-alkylphenols and p-alkylphenol ethoxylates
      were determined in water samples of the North Sea, the Elbe river, and its
      tributaries Schwarze Elster, Mulde, Saale and the Weisse Elster. The sampling
      sites of the Elbe river reached from Schmilka at the German-Czech border to
      Cuxhaven at the estuary. Samples of the North Sea were taken in the German Bight.
      Additionally, freshly deposed sediments of the River Elbe and its tributaries
      were analyzed. Partitioning coefficients of these compounds for the distribution
      between suspended particulate matter (SPM) and the aqueous phase were calculated
      for samples of the River Elbe at sampling site Geesthacht. The analytical
      procedure consisted of liquid-liquid extractions of the acidified water samples
      using dichloromethane. Sediments and SPM samples were extracted by Accelerated
      Solvent Extraction with n-hexane/acetone. Following a clean-up by HPLC, the
      analytes were derivatized with heptafluorobutyric acid anhydride and quantified
      using GC-MSD. The concentration ranges of the compounds analyzed in water samples
      of the Elbe river were as follows (in ng l(-1)): BPA 9-776, alkylphenols 10-221
      and alkylphenol ethoxylates 18-302. In sediment samples the concentrations were
      (in microg kg(-1) dry mass): BPA 66-343, alkylphenols 17-1378 and alkylphenol
      ethoxylates 30-1797. In samples of the North Sea the concentrations were
      generally about 1 order of magnitude lower. As shown by the concentration
      profiles following the River Elbe into the North Sea, the Elbe river must be
      considered as a major pollution source for the North Sea concerning the compounds
      analyzed. The SPM/water-partitioning coefficients calculated (mean values)
      amounted to: BPA 4.50, alkylphenols 5.52-5.58 and alkylphenol ethoxylates 5.60
      6.38. A comparison of the results with data from other surface waters showed that
      concentrations of these xenoestrogens in the River Elbe and its tributaries were
      relatively low. The evaluation of the data based on the lowest observable effect
      concentration (LOEC) for alkylphenols (endpoint: vitellogenin synthesis in male
      trout) indicated that the concentrations were well below the effectivity
      threshold.

PMID- 11592414
TI  - Isomer specific syntheses of chlorinated catechols and guaiacols relevant to pulp
      bleaching.
AB  - A variety of chlorinated catechols and guaiacols relevant to pulp bleaching were
      synthesized by employing fundamental differences in the acidities of phenolic
      hydroxyl groups in chlorinated catechols, and directive effects in guaiacols.

PMID- 11592415
TI  - Formation of volatile halogenated by-products during chlorination of isoproturon
      aqueous solutions.
AB  - The present paper deals with the formation of volatile halogenated by-products
      (POX) during the chlorination (160 mg/l) of aqueous solutions of the herbicide
      isoproturon (40 mg/l). Chlorination reactions have been carried out over 48 h, at
      ambient temperature, at two pHs (6 and 9) and in the presence or not of bromide
      ions (80 mg/l). The main results obtained have been as follows: (1) in the
      presence of bromide, isoproturon degradation is rather fast and it results
      affected by pH, complete isoproturon degradation is achieved within 1 and 15 min
      at pH 6 and 9, respectively; (2) in the absence of bromide herbicide degradation
      is slow (complete degradation is achieved within 180 min) and it is not affected
      by pH; (3) at pH 6, regardless of the presence of bromide, the maximum amount of
      POX formed is low (approximately 15 micromol X-/l) and remains constant during
      the reaction; (4) at pH 9 the amount of POX formed is far greater and
      continuously increases during the reaction, reaching a value of about 110
      micromol X-/l after 48 h; (5) two different groups of by-products have been
      identified by solid phase micro extraction (SPME)-gas chromatography (GC)-mass
      spectrometry (MS) for the reactions carried out with or without bromide; among
      them, aliphatic as well as aromatic by-products containing chlorine, bromine or
      both halogens are present even though the most abundant are halogenated-methane
      derivatives (haloforms); pH value affects the amount of these by-products but
      does not modify their chemical nature.

PMID- 11592416
TI  - Comparison of methods for determination of volatile organic compounds in drinking
      water.
AB  - Comparison of four methods including liquid-liquid extraction (LLE), direct
      aqueous injection (DAI), purge and trap (PAT) and head space (HS) were carried
      out in this work for determination of volatile organic compounds (VOCs) including
      trihalomethanes (THMs) in drinking water. This comparison is made especially to
      show the advantages and disadvantages and specifically the different detection
      limits (DL) that can be obtained for a given type of analysis. LLE is applicable
      only for determination of the THMs concentrations, while DAI, PAT, HS methods
      with different DL each of them are applicable for all VOCs, with PAT to be the
      most sensitive. Sampling apparatus and procedure for all these methods except of
      PAT are very simple and easy, but possible disadvantages for LLE and DAI are the
      low sensitivity and especially the detection only of THMs with LLE.

PMID- 11592417
TI  - Pyrolysis of oil sludge in a fluidised bed reactor.
AB  - The oil sludge of tanker cleaning was pyrolysed in fluidised bed reactors. Three
      experiments were conducted in a laboratory plant and two on a technical plant.
      Separation of oil from the solids and distribution of the oil products were
      investigated at temperatures from 460 degrees C to 650 degrees C. Between 70% and
      84% of the oil could be separated from the solids. Distribution of the oil
      products depended on the feed material and the pyrolysis conditions. The higher
      the temperature the more the oil was cracked into low boiling compounds. Under
      the conditions of pyrolysis carbon reduced gridiron to iron. Thus some solid
      fractions were pyrophoric and oxidised with high heat generation. Therefore the
      solid products have to be turned into inert substances. The fluidised bed
      pyrolysis is an adequate process to recycle oil sludge with high yields.

PMID- 11592418
TI  - Patterns in content of phenolic compounds in leaves of mountain birches along a
      strong pollution gradient.
AB  - The contents of individual low-molecular weight phenolic compounds (LMWPs) in
      mountain birch, Betula pubescens ssp. czerepanovii, leaves collected during 1996
      1998 in six plots 7-65 km south of the nickel-copper smelter at Monchegorsk, Kola
      Peninsula, NW Russia, were reported. A high-performance liquid chromatography
      electrospray ionisation-mass spectrometry (HPLC-ESI-MS) was used for the rapid
      identification of low-molecular weight phenolics. Quantification was performed by
      the analytical high-performance liquid chromatography with UV-detection. Contents
      of (+)-catechin and some gallic acid derivatives decreased significantly, and
      contents of flavonol glycosides slightly increased with the distance from the
      smelter. Hydroxycinnamic acid derivatives remained unaffected. These changes in
      birch leaf phenolics are probably related to the effect of environmental
      contamination on the biosynthetic reactions both in the shikimate and
      phenylpropanoid pathways.

PMID- 11592419
TI  - Investigation of the permeability of humic molecules using zeta potential
      measurements.
AB  - Zeta potential measurements have been performed on colloidal humate in the
      presence of differing concentrations of sodium ions at pH = 6.0. A series of
      calculations has been performed in which the radius of the humic colloid was
      varied until the predicted surface potential was equal to the experimentally
      determined zeta potential. The results of the calculations showed that as the
      ionic strength increases, the apparent radius of the colloid decreases. Similar
      calculations in which a model colloid was treated as a rigid sphere, i.e., the
      radius of the colloid was kept constant, failed to simulate the observed zeta
      potential measurements.

PMID- 11592420
TI  - The Henry's law coefficient of 2-nitrophenol over the temperature range 278-303
      K.
AB  - Although 2-nitrophenol has been identified as an important environmental chemical
      there is scarcity in the literature regarding the temperature dependence of its
      Henry's law coefficient, H. Here a bubble purge method was used to measure H for
      2-nitrophenol over the temperature range 278-303 K. A novel approach in the data
      treatment allowed correction of the data for non-equilibrium partitioning in the
      apparatus to obtain the true equilibrium H value. The experimentally derived
      temperature-dependent expression for H of 2-nitrophenol is lnH (M atm(-1)) =
      (6290/T (K)) - 16.6. The standard enthalpy and entropy of gas-to-liquid transfer
      for 2-nitrophenol in aqueous solution are -52.3 +/- 8.1 kJ mol(-1) and -138 +/-
      28 J mol(-1) K(-1), respectively. (Errors are 95% confidence intervals.)

PMID- 11592421
TI  - Chemical characteristics of organic aerosol in Bab-Ezzouar (Algiers).
      Contribution of bituminous product manufacture.
AB  - The organic compositions of atmospheric particulate matter from Bab-Ezzouar
      (Algiers) have been investigated to assess the air pollution levels suspected to
      be caused by asphalt product and yeast manufactures. After a medium-volume air
      sampling, soxhlet extraction, alumina elution and HPLC separation, the extracts
      were analysed by high-resolution gas chromatography (HRGC) and gas chromatography
      coupled to mass spectrometry (GC-MS). The composition of n-alkane and polycyclic
      aromatic hydrocarbons (PAH) fractions reflected the petrogenic origin from the
      emission of asphalt materials production in addition to vascular plant wax
      emissions. In contrast, microbial activities seemed to play the main role for the
      presence of n-alkanoic acids at Bab-Ezzouar. The sole nitrated polycyclic
      aromatic hydrocarbons (NPAH) observed, i.e., 2-nitrofluoranthene (2NFA), was very
      likely to arise from gas-phase photochemical reaction of parent PAH in the
      atmosphere. The total aerial levels ranged from 75 to 206 ng m(-3) for n-alkanes,
      from 153 to 345 ng m(-3) for n-alkanoic acids and from 44 to 100 ng m(-3) for PAH
      and NPAH. Although the samples were collected during the hot season, the levels
      of these pollutants seemed to be important and of environmental concern,
      especially for PAH species.

PMID- 11592422
TI  - Investigations on the sorption of phenols to dissolved organic matter by a QSAR
      study.
AB  - The sorption of various phenols to Aldrich-HA and BSA was investigated by solid
      phase microextraction (SPME). The Aldrich-HA sorption with log K(DOC)-values
      between 2 and 3 was determined, whereas the sorption to BSA with log K(DOC)
      values between 2 and 6 was much stronger. To enable an estimation of sorption
      constants a QSAR model was investigated. The linear free energy relationship
      (LFER) model showed a good correlation between the sorption constants and the log
      K(OW)-values with correlation coefficients of R = 0.910 and R = 0.878 for Aldrich
      HA and BSA, respectively.

PMID- 11592423
TI  - The evolution of the pH in Europe (1986-1997) using panel data.
AB  - The temporal evolution of pH values in precipitation over Europe during the
      period 1986-1997 is examined using panel data. The use of panel data techniques
      allows us to determine the temporal evolution of groups of stations rather than
      analyzing the temporal behavior of each of them. The analysis reveals three
      different temporal patterns: Peripheral, Central and French. We find a
      significant increasing trend (P < 0.00001) in both Peripheral and Central
      patterns. The annual increases are +0.057 pH-units yr(-1) and +0.022 pH-units yr(
      1) respectively. However the French pattern is characterized by a significant
      decreasing trend (P < 0.004) and the annual decrease is -0.022 pH-units yr(-1).
      The standard errors of panel data estimates are around 47% smaller than those of
      classical pooling and 32% smaller than aggregate time-series regression. The use
      of panel data produces higher R2 values than classical pooling and aggregate
      data. This technique takes into account the individual heterogeneity, allows a
      larger number of data points and improves the efficiency of the estimates. In
      general, the policies of governments to reduce pollutant emissions seem to be
      effective.

PMID- 11592424
TI  - A review of the environmental fate and aquatic effects of a series of C4 and C8
      oxo-process chemicals.
AB  - Environmental fate and aquatic effects data were examined for a series of C4
      (butyl acetate, 1-butanol, isobutyl alcohol) and C8 (2-ethylhexanol and 2
      ethylhexanoic acid) oxo-process chemicals. Manufacturing of these chemicals
      requires enclosed equipment, so environmental releases are generally limited to
      volatilization during their use, handling or transport. C4 compounds are more
      soluble and volatile, and would bind to soil and sediment to a lesser extent than
      C8 compounds. All five compounds were readily biodegradable based on OECD and
      APHA tests conducted up to 28 days. Atmospheric photo-oxidation half-lives range
      from 0.43 to 3.8 days. Toxicity data show that all five compounds pose generally
      low concern to fish, invertebrates, algae, and microorganisms. Overall, the data
      show that inadvertent releases of these compounds into the environment would be
      rapidly biodegraded in soil and water, volatilize to the atmosphere subject to
      photo-oxidation, while any residues remaining in water would pose a negligible
      threat to aquatic life.

PMID- 11592425
TI  - Sources of PM10 and sulfate aerosol at McMurdo Station, Antarctica.
AB  - Source contributions to PM10 and sulfate aerosol at McMurdo Station, Antarctica
      during the austral summers of 1995-1996 and 1996-1997 were estimated using
      Chemical Mass Balance (CMB) receptor modeling. The average PM10 (particles with
      aerodynamic diameters less than 10 microm) concentration at Hut Point, located
      less than 1 km downwind of downtown McMurdo, was 3.4 microg/m3. Emissions
      profiles were determined for potentially important aerosol source types in
      McMurdo: exposed soil, power generation, space heating, and surface vehicles.
      Soil dust, sea salt, combustion emissions, sulfates, marine biogenic emissions as
      methanesulfonate, and nitrates contributed 57%, 15%, 14%, 10%, 3%, and 1%,
      respectively, of average estimated PM10 at Hut Point (3.2 microg/m3). Soil dust,
      sea salt, and combustion sources contributed 12%, 8%, and 20%, respectively, of
      the average PM10 sulfate concentration of 0.46 microg/m3. Marine biogenic sources
      contributed 0.17 microg/m3 (37%). The remaining sulfate is thought to have come
      from emissions from Mt. Erebus or hemispheric pollution sources.

PMID- 11592426
TI  - Humic complexes of diethyl phthalate: molecular modelling of the sorption
      process.
AB  - The sorption mechanisms and complex formation between humic acid (HA) and a
      successively increasing number of diethyl phthalate (DEP) molecules have been
      studied theoretically using molecular mechanics, the number (n) of DEP molecules
      being varied from 1 to 30. The energy components of the single HA x nDEP
      complexes have been used as explanatory variables in a principal component
      analysis for exploring the presence of similarities/dissimilarities in the
      energetic properties of the individual xenobiotic complexes. The sorption can be
      explained in terms of a two-step mechanism. Absorption takes place as long as the
      host humic acid structure offers (a) enough internal docking space and (b)
      favorable interactions (energy release) with the guest molecule. This takes place
      for up to 7 DEP molecules. Further increase in the number to 30 DEP molecules
      will, due to the lack of free available internal voids, lead to surface
      controlled adsorption. The two-step sorption process apparently results in (a) a
      linear increase in energy gain by DEP bonds, and similarly (b) a constant
      incremental rise in molecular properties of the complexes such as volume and
      surface area. Three outstanding observations emerge: (1) Structural features at
      the atomic level (nanochemistry), such as partial atomic charges and high
      aromaticity of the humic acid, are observed to be dominating the intermolecular
      interactions in the complexes at the specific sorption sites. (2) Torsional
      relief and favorable changes in bonding energy also prevail for the growing
      complex. The latter indicates both the structural flexibility of the HA host and
      the stabilizing effect of DEP on the complex, by filling of the voids within the
      HA molecule. (3) The intermolecular forces are described mainly by hydrogen bonds
      (electrostatic energy) and interactions between dipole-dipole, such as carboxylic
      functions and uncharged moieties such as aromatic rings (van der Waals energy).

PMID- 11592427
TI  - Depth profiles of volatile halogenated hydrocarbons in seawater in the Bay of
      Bengal.
AB  - Measurements were made of bromocarbons (CHBr3 and CH2Br2), iodocarbons (CH2I2 and
      CH2ClI), and dimethylsulfide (DMS, CH3SCH3) in seawater collected from the Bay of
      Bengal under tropical stratified conditions. These compounds showed different
      depth profiles, characteristic of each group. CH2I2 and CH2ClI showed very
      similar depth profiles to chlorophyll-a, suggesting their production by
      phytoplankton followed by rapid decay in seawater. The CH2I2 maximum at a depth a
      little below the CH2ClI maximum was consistent with its more significant
      photolytic decay. The bromocarbons were less localized in their distributions
      than were the iodocarbons, suggesting their longer residence time in seawater
      after their release from phytoplankton. Both of these profiles were different
      from the pattern of DMS, which had its maxima above the chlorophyll-a maximum
      layer near the surface.

PMID- 11592428
TI  - Factors on the formation of disinfection by-products MX, DCA and TCA by
      chlorination of fulvic acid from lake sediments.
AB  - [3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone] (MX) and chlorinated
      acetic acids such as dichlorinated acetic acid (DCA) and trichlorinated acetic
      acid (TCA) have always been the focus of disinfection by-products (DBPs) studies.
      In order to find out the influences of reaction time, TOC, chlorine dose, pH and
      temperature on the formation of MX, DCA and TCA, we extracted fulvic acid (FA)
      from the sediment of Tai Lake, and conducted simulated chlorination of samples
      rich in FA. Results showed positive relationship between TOC and the yields of
      MX, DCA and TCA. But the influences of pH, chlorine dose, reaction time, and
      temperature are quite complex. The optimal chlorination condition for the
      formation of MX is pH = 2, T = 45 degrees C, C/Cl2 = 1/4, t = 12 h. Lower pH,
      longer time, greater chlorine dose can result in greater yield of both DCA and
      TCA, and there is a strong linear relationship between the formation of DCA and
      TCA.

PMID- 11592429
TI  - Fate of the herbicide 14C-terbuthylazine in Brazilian soils under various
      climatic conditions.
AB  - 14C-terbuthylazine was applied to three Brazilian soils in closed aerated
      laboratory microcosms, both under standardized and under natural Brazilian
      climate conditions. Volatilization from soil to air, leaching from soil to
      percolate water, and transport from upper to deeper soil layers were higher in
      sandy soil than in clay soil and in organic soil. Mineralization of 14C
      terbuthylazine to 14CO2 was higher in sandy soil than in clay and organic soils
      under standardized climatic conditions, whereas it was higher in organic soil
      than in sandy soil under Brazilian summer conditions. Under natural Brazilian
      summer conditions, leaching as well as vertical transport within the soil were
      enhanced as compared to standardized climate conditions comprising lower
      precipitation rates; volatilization was strongly reduced under high irrigation
      conditions.

PMID- 11592430
TI  - Historical aspects and perspectives in homocysteine research.

PMID- 11592431
TI  - The importance of hyperhomocysteinemia as a risk factor for diseases: an
      overview.
AB  - Hyperhomocysteinemia is the result of a disturbed methionine metabolism. It
      results from enzyme and/or vitamin deficiency. Epidemiological studies have
      proven, that hyperhomocysteinemia is a risk factor for atherosclerotic
      cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous
      thrombosis. Conflicting results come from prospective studies. Trials which are
      now in progress may clarify the "causality" of high homocysteine concentrations
      and will assess the value of homocysteine-lowering therapy. The induction of the
      atherogenic process by hyperhomocysteinemia seems to be associated with an
      alteration of endothelial and smooth muscle cell function leading to an
      accelerated formation of reactive oxygen species. An increased endothelial
      expression of adhesion molecules will then lead to an enhanced deposition of
      oxidized LDL in the vessel wall with the formation of foam cells. Additionally,
      hyperhomocysteinemia interferes with the coagulation system and thus also has
      prothrombotic effects. There is a high prevalence of hyperhomocysteinemia as a
      sign of a vitamin deficiency in elderly subjects which strongly increases with
      age. Elderly people have a high frequency of vitamin B12 deficiency which can be
      diagnosed more reliably by the measurement of serum methylmalonic acid (MMA)
      level than by serum vitamin B12. Subjects following a strict vegetarian diet also
      have a high prevalence of hyperhomocysteinemia caused by functional vitamin B12
      deficiency (increased MMA level). Last but not least, hyperhomocysteinemia is a
      factor in the pathogenesis of neural tube defects and pre-eclampsia. An early
      diagnosis of vitamin B12 deficiency is important for the prevention of
      neurological damages. Homocysteine should be measured in patients with a history
      of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia,
      in renal patients, in obese subjects, in elderly people, in postmenopausal women,
      and in early pregnancy. A specific diagnosis of an underlying vitamin deficiency
      is important for adequate treatment. Individuals with homocysteine level >12
      micromol/l should increase and/or supplement their dietary intake of vitamins.

PMID- 11592432
TI  - Pre-analytical conditions affecting the determination of the plasma homocysteine
      concentration.
AB  - In the past decade, moderately elevated homocysteine concentration has achieved
      wide-spread recognition as an independent risk factor for vascular diseases, such
      as stroke and peripheral vascular disease, as well as for an impaired nutritional
      status. In general, EDTA plasma is used for the determination of homocysteine.
      However, from the pre-analytical point of view it is important, that, when plasma
      is not separated from blood cells within 30 minutes, homocysteine levels increase
      in samples significantly by about 10% per hour. This 10% increase is very
      important, because the normal range is between 5 and 15 micromol/l and moderately
      elevated homocysteine concentrations above 15 micromol/l may signify an increased
      risk of vascular disease. These preliminary cut-off points show that there is
      only a small difference between normal and moderately elevated homocysteine
      concentrations. Most blood samples are obtained outside the hospital, and in
      these cases homocysteine concentrations will be falsely elevated, if no
      precautions are taken, such as immediate centrifugation and separation of plasma
      and cells. This aspect is critical both for clinical studies and in patient care
      outside the hospital. But even in the hospital it is difficult to separate plasma
      and cells within 30 minutes. In the past, different approaches were adopted to
      solve this problem. Potential stabilisers were sodium fluoride (4 g/l) and 3
      deazaadenosine (100 micromol/l). Sodium fluoride initially increased the
      homocysteine concentration, which dropped below the initial values after 72 h. On
      the other hand, 3-deazaadenosine stabilised homocysteine concentrations for 24 h,
      but increased it within 72 h by roughly 10%. However, this stabiliser is
      restricted to HPLC technology but does not work reliably with immunoassays. Lysis
      of blood stabilised homocysteine, but homocysteine concentrations were
      systematically lower requiring totally new reference ranges. In addition, acidic
      citrate (0.5 mol/l) was evaluated, which seems to stabilise plasma homocysteine
      concentrations at ambient temperatures for several hours. However, small but
      systematic deviations at baseline are observed. This stabilisation procedure does
      not interfere with immunoassays. Because immunoassays will be the future method
      of choice for robust and easy to perform homocysteine measurements, because they
      easily allow the analyses of high sample numbers, homocysteine stabilisation in
      whole blood is still an important matter. It must be solved before homocysteine
      determinations are introduced as a general screening for vascular risk factors in
      non-specialist laboratories.

PMID- 11592433
TI  - Total plasma homocysteine and related amino acids in end-stage renal disease
      (ESRD) patients measured by gas chromatography-mass spectrometry--comparison with
      the Abbott IMx homocysteine assay and the HPLC method.
AB  - Increased concentrations of homocysteine probably contribute to the high
      cardiovascular morbidity and mortality in hemodialysed end-stage renal disease
      (ESRD) patients and are determined by a variety of factors such as age, residual
      renal function, and vitamin status. Fasting plasma concentrations of total
      homocysteine, methionine, cysteine, and cystathionine were determined by gas
      chromatography-mass spectrometry (GC-MS) in 131 ESRD patients receiving daily
      oral folate (160-320 microg) and vitamin B6 (10-20 mg) supplements.
      Concentrations of homocysteine determined by GC-MS were compared with those
      measured by high-performance liquid chromatography (HPLC) and an
      immunofluorescence method (IMx analyzer) using Passing-Bablok regression
      analysis. Mean plasma concentration of total homocysteine determined by GC-MS
      (28.7+/-11.9 micromol/l [mean+/-SD]) was significantly lower than that determined
      by HPLC (34.0+/-14.5 micromol/l; p<0.001) or IMx (32.4+/-13.9 micromol/l;
      p<0.001). A close correlation existed between GC-MS and HPLC (r=0.931; y=1.203
      x+0.279) and GC-MS and IMx (r=0.896; y=1.105 x+0.766). Linear regression analysis
      showed positive correlations between plasma concentrations of homocysteine and
      cysteine (r=0.434; p<0.001) and homocysteine and cystathionine (r=0.187;
      p=0.032). Plasma concentrations of homocysteine correlated negatively with folate
      (r=-0.281; p=0.001) and vitamin B12 (r=-0.229; p=0.009). GC-MS proved to be a
      sensitive and reliable method for the determination of total plasma homocysteine
      and related amino acids. Despite vitamin supplementation, ESRD patients requiring
      chronic maintenance hemodialysis, have high plasma concentrations of
      homocyst(e)ine which seems to be metabolized mainly within the transsulfuration
      pathway, while remethylation to methionine seems to be disturbed.

PMID- 11592434
TI  - Is hyperhomocysteinemia due to the oxidative depletion of folate rather than to
      insufficient dietary intake?
AB  - Hyperhomocysteinemia is considered as a risk factor for cardiovascular diseases.
      Usually, an inverse relationship exists between homocysteine and folate levels,
      and supplementation with folate lowers homocysteine concentrations in patients.
      Therefore, hyperhomocysteinemia is mainly ascribed to the insufficient dietary
      intake of folate. Hyperhomocysteinemia has also been observed in infections and
      inflammatory diseases. Oxidative stress appears to be involved in the
      pathogenesis of these disorders, and associations have been found between
      homocysteine and e.g., neopterin concentration. Increased neopterin concentration
      indicates immune system activation and also allows an estimate of thus elicited
      oxidative stress. It may be relevant that the active cofactor, tetrahydrofolate,
      is very susceptible to oxidation. Immunologically induced oxidative stress could
      lead to folate depletion resulting in hyperhomocysteinemia. Thus,
      hyperhomocysteinemia in patients can be considered as an indirect consequence of
      hyperconsumption of antioxidant vitamins during prolonged states of immune
      activation.

PMID- 11592435
TI  - Hyperhomocysteinemia in advanced age.
AB  - Nutritional deficiency does not fit the view of life in an affluent society and
      in fact typical diseases resulting from a deficiency of vitamins are actually a
      rarity. On the other hand, elderly people must be regarded as an essential risk
      group for vitamin deficiency because of various influence factors. The frequency
      of lowered vitamin concentrations in the blood increases with age. However,
      knowledge on the consequences for this population is insufficient, especially for
      hyperhomocysteinemia. Investigations have yielded the following results: 1.
      Hyperhomocysteinemia often occurs with advanced age; 2. Impairment of physical
      condition or social situation seems to increase the risk of hyperhomocysteinemia;
      3. Administration of the vitamins B6, B12 and folate causes a significant
      decrease of elevated serum homocysteine concentrations in older persons.
      Homocysteine-lowering treatment should improve the prevention of chronic
      diseases. The question is which effects can be expected from such treatment in
      the elderly. Because of its great importance for both the persons concerned and
      society in general hyperhomocysteinemia in advanced age requires further
      systematic examination.

PMID- 11592436
TI  - Genetic defects as important factors for moderate hyperhomocysteinemia.
AB  - The genes for the enzymes methylenetetrahydrofolate reductase (MTHFR), methionine
      synthase (MS), methionine synthase reductase (MSR) and cytathionine-beta-synthase
      (CBS) play an important role in homocysteine metabolism. Rare mutations in these
      genes cause severe hyperhomocysteinemia and clinical symptoms. Growing interest
      has focused on common mutations with moderate effects on homocysteine levels. We
      studied 280 subjects of different age groups for the following mutations:
      MTHFR677C-->T and 1298A-->C, MS2756A-->G, MSR66A-->G and the 68 bp insertion in
      the CBS gene. The median value for homocysteine increased significantly with age
      (median homocysteine levels: 7.5, 12.4 and 16.5 micromol/l in the age groups 20
      43, 65-75 and 85-96 years, respectively). The genotypes of the MTHFR677C-->T
      mutation were associated with differences in plasma homocysteine levels, but
      without reaching significance. Individuals homozygous for the MTHFR677C-->T
      mutation had a 2.3 micromol/l higher median homocysteine level compared to
      individuals with the wild-type allele. This effect was pronounced in combination
      with low folate levels and abolished with higher folate in plasma. For the other
      three mutations no association with homocysteine values could be determined. The
      analysis of homocysteine metabolite cystathionine by backward regression analysis
      revealed a significant correlation of the MS2756A-->G mutation with cystathionine
      level. This increase could indicate a disturbed remethylation. In summary, larger
      and homogeneous study populations are necessary to quantify the small effects of
      common mutations on homocysteine levels. This may also be the reason that no
      effects of genetic interactions between two genotypes were observed.

PMID- 11592437
TI  - Heterogeneity of the association between plasma homocysteine and atherothrombotic
      disease: insights from studies of vascular structure and function.
AB  - Among individuals with severe hyperhomocysteinaemia, there is a striking
      heterogeneity in the severity of the clinical features. This observation
      demonstrates that factors must exist that modulate the relationship between
      hyperhomocysteinaemia and clinical disease. Investigations of the association
      between mild-to-moderate hyperhomocysteinaemia and atherothrombotic disease also
      suggest heterogeneity in the association between plasma homocysteine levels and
      1) clinical disease; 2) angiographic and echographic estimates of the extent of
      atherosclerosis; 3) arterial stiffness; 4) endothelial function; and 5)
      procoagulant status. The commonly held view that homocysteine is a vasculotoxic
      substance that promotes atherogenesis by causing endothelial damage is
      incomplete, because it cannot explain this heterogeneity. I suggest that
      homocysteine may have both prothrombotic and proatherogenic properties, but that
      there are strong, as yet unidentified enhancing and protective factors, the
      prevalence of which may differ among populations. This concept could account for
      some of the observed heterogeneity. Identifying these factors would be of major
      clinical importance and would provide crucial mechanistic insights.

PMID- 11592438
TI  - Hyperhomocysteinemia as a risk factor for venous thrombosis.
AB  - Classical homocystinuria is associated with arterial vascular diseases and venous
      thrombosis. In the last decade, several studies have been published indicating
      that even mild hyperhomocysteinemia is a risk factor for venous thrombosis. The
      677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an
      important cause of mild hyperhomocysteinemia, but this polymorphism does not seem
      to be a risk factor for venous thrombosis. Studies on the interaction between
      hyperhomocysteinemia and other thrombotic risk factors are conflicting. Little is
      known about the pathophysiology of venous thrombosis in hyperhomocysteinemia.
      Several mechanisms proposed for vascular disease may be applied to venous
      thrombosis as well. However, up to now there is no satisfying model which might
      explain a thrombophilic state at plasma homocysteine concentrations in the range
      of mild hyperhomocysteinemia. The results of a first clinical intervention study
      are expected in 2002. As the results are pending, clinicians could perform
      homocysteine measurements in patients with venous thrombosis if screening for
      thrombophilia is indicated. Vitamin supplementation could be prescribed if
      homocysteine levels are elevated. However, the patient should be informed about
      the uncertainty of the benefits of vitamin supplementation.

PMID- 11592439
TI  - Hyperhomocysteinaemia in patients with peripheral arterial occlusive disease.
AB  - In the Western world, cardiovascular disease is still the most common cause of
      death. Over the past decade it has become clear that apart from common risk
      factors, high concentrations of total homocysteine are relavant to the process of
      atherosclerosis, especially in the development of premature vascular disease.
      Hyperhomocysteinaemia (HHC) can be found in 25-32% of the patients with premature
      peripheral arterial occlusive disease (PAD). Retrospective and prospective
      studies, evaluating the clinical course of patients with PAD, showed significant
      associations between high concentrations of total homocysteine and the severity
      of atherosclerosis and with a more rapid disease progression and mortality rates.
      HHC can be treated with vitamin B6 and folic acid. Although there may be
      indications that there is a protective effect of treatment, prospective
      randomized clinical trials are urgently needed to unravel the role of HHC and its
      treatment in patients with premature PAD.

PMID- 11592440
TI  - Homocysteine, vascular dementia and Alzheimer's disease.
AB  - There is some evidence from recent observational studies that
      hyperhomocysteinemia is a risk factor for cognitive dysfunction, including
      Alzheimer's disease and vascular dementia. There are only a few intervention
      studies, and the results are disappointing for such a frequent disease.
      Prospective double-blind and placebo-controlled intervention studies are not
      available. If homocysteine-lowering therapy will be in the running for the
      prevention and treatment of dementia, we must be able to diagnose the disease at
      a preclinical stage (i.e. 5 or 10 or 20 years before the disease becomes
      clinically overt for Alzheimer's disease). At the moment, there are insufficient
      data to support a vitamin B12, B6 or folate therapy in the prevention or
      treatment of patients with dementia.

PMID- 11592441
TI  - Homocysteine in cerebrovascular disease: an independent risk factor for
      subcortical vascular encephalopathy.
AB  - Hyperhomocysteinemia is a risk factor for obstructive large-vessel disease. Here,
      we studied plasma concentrations of homocysteine and vitamins in patients
      suffering from subcortical vascular encephalopathy (SVE), a cerebral small-vessel
      disease leading to dementia. These results were compared to the homocysteine and
      vitamin plasma concentrations from patients with cerebral large vessel disease
      and healthy control subjects. Plasma concentrations of homocysteine, vascular
      risk factors and vitamin status (B6, B12, folate) were determined in 82 patients
      with subcortical vascular encephalopathy, in 144 patients with cerebral large
      vessel disease and in 102 control subjects. Patients with SVE, but not those with
      cerebral large-vessel disease, exhibited pathologically increased homocysteine
      concentrations in comparison with control subjects without cerebrovascular
      disease. Patients with SVE also showed lower vitamin B6 values in comparison to
      subjects without cerebrovascular disease. Logistic regression analysis showed
      that homocysteine is associated with the highest risk for SVE (odds ratio 5.7; CI
      2.5-12.9) in comparison to other vascular risk factors such as hypertension, age
      and smoking. These observations indicate that hyperhomocysteinemia is a strong
      independent risk factor for SVE.

PMID- 11592443
TI  - Hyperhomocysteinemia in chronic renal failure patients: relation to nutritional
      status and cardiovascular disease.
AB  - A moderate increase in plasma total homocysteine (tHcy) is considered to be an
      independent risk factor for cardiovascular disease (CVD) in the general
      population. Almost all chronic renal failure (CRF) patients have plasma
      concentration of tHcy that is elevated 3 to 4 times above normal. The prevalence
      of CVD, diabetes mellitus, malnutrition and hypoalbuminemia is high in CRF
      patients. Previous investigations have focused on the role of vitamin status on
      plasma tHcy in CRF patients, but little information exists on the influence of
      nutritional status and hypoalbuminemia on plasma tHcy in CRF, although a
      substantial fraction of tHcy (>70%) is protein-bound, mainly to albumin. Our
      study in patients with end-stage renal disease showed that more than 90% of the
      patients had elevated plasma tHcy levels, which were higher in patients with
      normal nutritional status than in malnourished patients. Moreover, plasma tHcy
      was inversely correlated with subjective global nutritional assessment (high
      values denote malnutrition) and positively correlated with serum albumin and
      protein intake. Hence, it seems likely that serum-albumin is a strong determinant
      of plasma tHcy in CRF patients and this may contribute to the lower tHcy levels
      in malnourished patients. Patients with diabetes mellitus had lower serum-albumin
      and plasma tHcy than non-diabetic patients, irrespective whether they were
      malnourished or not. Patients with CVD had lower (although still elevated) plasma
      tHcy levels than those without CVD. An explanation may be that the prevalence of
      diabetes mellitus, malnutrition and hypoalbuminema, i.e. factors that decrease
      tHcy, was higher in patients with CVD, which may explain why they had less
      elevated values. Assuming that hyperhomocysteinemia carries an independent risk
      of CVD, this implies that almost all CRF patients are exposed to this risk. CRF
      patients with CVD had a higher prevalence of malnutrition, hypoalbuminemia and
      diabetes mellitus, which was associated with a lower plasma Hcy level. This may
      explain why plasma tHcy was lower (although still abnormally high) in patients
      with CVD than in patients without CVD. The lower tHcy levels in CVD patients do
      not contradict the assumption that hyperhomocysteinemia is a risk factor for CVD
      since almost all patients are exposed to this risk, and other factors might be
      present that confound the relationship between the absolute tHcy levels and CVD.
      Our findings imply that nutritional status and serum albumin, as well as the
      presence of diabetes mellitus, should be taken into consideration when evaluating
      tHcy as a risk factor for CVD in CRF patients.

PMID- 11592442
TI  - Vascular dysfunction in hyperhomocyst(e)inemia. Implications for atherothrombotic
      disease.
AB  - Elevated plasma homocyst(e)ine is currently accepted as a major, independent risk
      factor for atherosclerosis and venous thrombosis. Even moderate
      hyperhomocyst(e)inemia is prospectively associated with increased risk of
      mortality in patients with cardiovascular disease. However, the underlying
      mechanisms resulting in vascular damage are not clearly defined. The endothelium
      exerts fundamental control on the vascular tone, coagulation and fibrinolysis.
      Injury to the endothelium followed by dysfunction is an early key event preceding
      manifestation of vessel pathology. Acute and chronic exposure of endothelium to
      homocyst(e)ine induces impairment of endothelial function associated with altered
      homeostasis and morphologic changes of the vessel wall. Investigations of the
      role of homocyst(e)ine in the endothelium-dependent function in healthy subjects
      and cardiovascular patients have recently added important clinical insight with
      implications for the treatment of cardiovascular disease. Importantly, the
      damaging effects of hyperhomocyst(e)inemia on endothelial function are, at least
      in part, reversible in patients with established vascular disease, supporting
      further the hypothesis that homocyst(e)ine-lowering through vitamin
      supplementation may have vasoprotective effects.

PMID- 11592444
TI  - Homocysteine, cystathionine, methylmalonic acid and B-vitamins in patients with
      renal disease.
AB  - Moderate hyperhomocysteinemia is very frequent in renal patients. Aside from
      homocysteine (HCY) itself, the metabolites methylmalonic acid (MMA) and
      cystathionine (CYS) supply further information about disturbances in HCY
      metabolism. In two groups of renal patients, transplant and hemodialysis
      patients, we measured HCY, MMA and CYS and evaluated their diagnostic value for
      impaired HCY metabolism due to vitamin deficiency and renal insufficiency. We
      investigated serum samples from 63 transplant patients and 38 patients undergoing
      hemodialysis. HCY, MMA and CYS were assayed by gas chromatography-mass
      spectrometry, vitamin B6 by HPLC, B12 and folate by chemiluminescence
      immunoassay. The determination of HCY, MMA, and CYS in renal patients provides
      specific information about intracellular disturbances of HCY metabolism. The
      frequency of increased metabolite levels in renal patients was much higher than
      the frequency of lowered vitamin concentrations in serum. Furthermore, the
      metabolite levels in transplant patients were only moderately increased, whereas
      they were strongly increased in patients on hemodialysis (HCY 19.2 vs. 28.8
      micromol/l, MMA 292 vs. 1025 nmol/l, CYS 733 vs. 2711 nmol/l). Our findings may
      support the use of MMA determination in the diagnosis of vitamin B12 deficiency
      in renal patients. Compared to vitamin B12 deficiency, renal dysfunction itself
      appears to cause only a modest elevation in serum MMA. Regression analysis
      revealed that the moderate elevation of HCY and CYS in transplant patients is
      mainly a consequence of impaired remethylation of HCY to methionine with
      activated transsulfuration, whereas the mildly elevated MMA level is attributable
      to renal dysfunction. In patients on hemodialysis, all three metabolites were
      markedly elevated, indicating a strongly disturbed HCY metabolism. Based on a
      backward regression, we discovered that the HCY metabolism was strongly disturbed
      by renal insufficiency and vitamin deficiency. The markedly elevated HCY level
      was mainly attributable to functional vitamin B12 deficiency indicated by high
      MMA, and the strong CYS elevation was due to renal dysfunction and inhibition of
      this pathway by low levels of vitamin B6. In conclusion, besides HCY, the
      determination of MMA and CYS levels supports an early diagnosis of B-vitamin
      deficiency in renal patients. MMA is a more sensitive indicator of intracellular
      vitamin B12 deficiency than vitamin B12 in serum.

PMID- 11592445
TI  - Hyperhomocysteinemia is related to residual glomerular filtration and folate, but
      not to methylenetetrahydrofolate-reductase and methionine synthase polymorphisms,
      in supplemented end-stage renal disease patients undergoing hemodialysis.
AB  - Glomerular filtration is one of the major determinants of plasma total
      homocysteine (tHcy). To evaluate the respective roles of residual glomerular
      filtration (by measuring a specific protein marker, cystatin C), genetic
      polymorphisms and nutritional status in tHcy blood levels in end-stage renal
      disease patients (ESRD) under hemodialysis and supplemented with folate, we
      measured tHcy, folate, vitamin B12 (B12), creatinine, cystatin C, albumin and C
      reactive protein and determined the polymorphism of methylenetetrahydrofolate
      reductase (MTHFR) (C677T and A1289C) and of methionine synthase (MS) (A2756G) in
      114 ESRD patients before hemodialysis and 76 control subjects. All patients
      received a folate supplementation of 700 microg/day. Hyperhomocysteinemia was
      observed in all patients and exceeded the upper normal limit by 2-fold in 52.4%
      of the patients. Serum folate was significantly increased and the B12 level was
      not different from controls. Folate, Cystatin C and creatinine were significantly
      correlated to tHcy, while no correlation was found between tHcy, albumin and C
      reactive protein. No difference in genotype frequency between ESRD patients and
      controls was found for MTHFR A1289C and MS A2756G. The MTHFR 677TT genotype was
      less frequent and was associated with a significantly higher tHcy level in
      patients. Folate and residual glomerular filtration estimated by cystatin C and
      creatinine levels were two independent determinants of tHcy in ESRD patients.
      These data suggest that hyperhomocysteinemia is a consequence as well as a
      complicating factor of renal failure.

PMID- 11592446
TI  - Effect of treatment of hypothyroidism on the plasma concentrations of neuroactive
      steroids and homocysteine.
AB  - Autoimmune thyroiditis with hypothyroidism is frequently accompanied by symptoms
      of psychiatric disorders and atherogenic changes in lipid metabolism. Recent
      studies suggest that some neuroactive steroids and homocysteine are involved in
      the pathophysiology of both disorders. Homocysteine metabolism may be affected by
      some steroids. We were interested if the treatment of hypothyroidism would affect
      the above factors. We studied plasma concentrations of allopregnanolone,
      pregnenolone sulfate, dehydroepiandosterone and its sulfate, progesterone,
      estradiol and homocysteine in 14 patients (12 women, 2 men) during the 3-month
      treatment with levothyroxine. Steroids and thyroid function were monitored by
      measuring thyrotropin, free triiodothyronine, free thyroxine and levels of
      thyroid antimicrosomal antibodies and antibodies to thyroglobulin. We have found
      that with the restoration of the thyrotropin level, free triiodothyronine, free
      thyroxine and homocysteine levels decreased, but the levels of steroids were not
      significantly altered. Steroid concentrations correlated negatively with the
      level of thyroid antimicrosomal antibodies.

PMID- 11592447
TI  - Hyperhomocysteinaemia and human reproduction.
AB  - Mild hyperhomocysteinaemia has been identified as a risk factor for arterial
      disease and venous thrombosis. In 1991, elevated homocysteine concentrations were
      also suggested to be associated with neural tube defects (NTD). Since then this
      relationship has been reported frequently, as well as the relationship between
      NTD and the 677 C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR)
      gene. Meanwhile, disturbances in the homocysteine metabolism have also been
      reported as a risk factor for early pregnancy loss and for other congenital birth
      defects. However, besides embryonic or foetal consequences, hyperhomocysteinaemia
      has also been described as a cause of maternal obstetric complications such as
      pre-eclampsia. This review is concerned with the role of hyperhomocysteinaemia in
      human reproduction.

PMID- 11592448
TI  - Homocysteine in postmenopausal women and the importance of hormone replacement
      therapy.
AB  - Homocysteine (Hcy) has been shown to damage the vascular endothelial cells,
      contributing to atherothrombosis. The increase in plasma Hcy levels with natural
      menopause suggests a close relationship between Hcy metabolism and estrogen
      status and proposes one of the mechanisms through which menopause unfavorably
      affects cardiovascular disease risk in women. In addition to the prevention of
      osteoporosis, hormone replacement therapy (HRT) lowers Hcy levels in
      postmenopausal women. The first report by van der Mooren et al., demonstrated in
      an uncontrolled study a significant reduction (11%) in fasting serum Hcy level
      after 6 months of treatment with sequentially combined estradiol-dydrogesterone
      therapy in 21 healthy postmenopausal women. This effect was particularly evident
      in women with initially elevated baseline serum Hcy concentrations. Similar
      results were found in other studies in which women were treated with various
      transdermal as well as oral HRT regimens, although two studies could not confirm
      these findings. All these studies were uncontrolled, and three of them consisted
      of a relatively small number of participants. Therefore, they remained
      inconclusive. Three randomized controlled trials on HRT and Hcy were published to
      date, confirming that postmenopausal HRT reduces circulating levels of Hcy.
      Current and recent HRT use is associated with a slight increased risk of breast
      cancer. As a result of this, research has centered on finding compounds that can
      prevent the consequences of estrogen deficiency, without the potential risk of
      HRT. Raloxifene, referred to as a Selective Estrogen Receptor Modulator (SERM),
      has the potential as a viable alternative to HRT. Recently, two randomized
      controlled trials demonstrated that raloxifene lowers plasma Hcy levels in
      postmenopausal women, similar to the reduction obtained with HRT. Little is known
      about the mechanisms underlying the HRT-associated lowering of plasma Hcy.
      Proposed mechanisms relate to an increase in kidney methionine synthase activity
      or may be related to the transamination of methionine. We conclude that HRT
      decreases plasma Hcy levels in postmenopausal women and that the strongest
      reductions can be achieved in women with the highest concentrations.

PMID- 11592449
TI  - Does a single vitamin B-supplementation induce functional vitamin B-deficiency?
AB  - In a pilot study we measured the effect of three different combinations of the
      vitamins B6, folate and B12 on the serum concentrations of homocysteine,
      cystathionine and methylmalonic acid in five healthy young men without
      hyperhomocysteinemia. The results indicate that there are still undescribed
      interactions between vitamin B6 and folate, suggesting that these two vitamins
      should be given together to avoid depletion of the one not given. With regard to
      the well known metabolic pathways of methionine and cysteine, this confirms the
      hypothesis that a combined supplementation with the vitamins B6 and folate (and
      B12) is superior to folate alone in order to lower homocysteine.

PMID- 11592450
TI  - Palma de Mallorca meeting tackles issues of calibration and verification.

PMID- 11592451
TI  - Authorship is broken.

PMID- 11592452
TI  - Boundary violations: a culture-bound syndrome.
AB  - A backlash against the self-actualizing psychotherapy movements of the 1960s and
      1970s in concert with recent concerns about professional sexual misconduct has
      led some forensic psychiatrists to redefine many routine components of therapy as
      boundary behaviors. This concern has been followed by the development of
      conservative guidelines for how therapists should conduct themselves at the newly
      defined boundary crossings so as to avoid "violations." The slippery-slope
      argument that seemingly innocuous boundary crossings may lead inexorably to
      professional sexual misconduct has lent an urgency and legitimacy to the
      guideline enterprise, obscuring the perspective that the newly postulated
      boundaries do not represent the consensus of practitioners in the field.
      Otherwise highly controversial claims about what is ethical and proper behavior
      in psychotherapy gain a mantle of incontrovertibility when linked to predictions
      that ignoring published boundary guidelines will result in damage to patient and
      litigation against therapist. In this article, three widely advanced boundary
      guidelines are examined (therapist neutrality, therapist anonymity, and stable
      fee policy) for coherence and relevance to the richly diverse practice of
      psychotherapy.

PMID- 11592453
TI  - Commentary: boundaries, culture, and psychotherapy.

PMID- 11592454
TI  - Commentary: treatment boundaries--flexible guidelines, not rigid standards.

PMID- 11592455
TI  - Commentary: the therapeutic process and professional boundary guidelines.

PMID- 11592456
TI  - Is serial homicide really increasing?
AB  - Close examination of the available crime data reveals little scientific support
      for the widely held belief that serial homicide is frequent and increasing. The
      author argues that the dramatic changes in homicide clearance rates, incidence of
      murders with unknown motives, and victim gender data point to a likely increase,
      not in serial murder, but in contract murder. This type of killing appears to be
      having a significant impact on society; yet there has been a complete absence of
      forensic psychiatric study of this crime, a circumstance that needs to change.

PMID- 11592457
TI  - A clinical study of competency to consent to treatment in pediatrics.
AB  - A 19-item competency questionnaire for pediatric patients (CQ-Peds) was used to
      evaluate competency to consent to treatment in pediatric outpatients and
      inpatients at two university hospitals. Sixty-nine consecutive English-speaking
      pediatric outpatients were studied at Hospital A, and 23 consecutive English
      speaking pediatric inpatients were studied at Hospital B. Demographic data were
      statistically analyzed using the chi-square test, and there were no significant
      differences between the competent and incompetent groups (using CQ-Peds scores
      and cutoffs). CQ-Peds scores correlated highly with age (r = .947, p < .003;
      Outpatient Hospital A). Using the Child Behavior Checklist (CBCL) and the
      Pediatric Symptom Checklist (PSC) as a screen for psychopathology, the presence
      of psychiatric disturbance, per se, did not correlate with low CQ-Peds scores,
      nor was there a statistical difference between children from Spanish-speaking
      households and those from English-speaking households (Inpatient Hospital B).
      Overall, the children scored well on the CQ-Peds and demonstrated a good
      appreciation for their illnesses and treatment. The CQ-Peds score correlated
      highly with the that on the Wechsler Intelligence Scale for Children Revised
      Edition (WISC-R) vocabulary, comprehension, and similarities subtests and also
      with the Wide-Range Achievement Test-III (WRAT-III) reading assessment score
      (Inpatient Hospital B).

PMID- 11592458
TI  - Seclusion practice in a Canadian forensic psychiatric hospital.
AB  - In this study, seclusion practice was examined in a multilevel, secure
      psychiatric hospital, serving federally sentenced individuals in the Prairie
      Region, as defined by the Correctional Service of Canada. Between August 1996 and
      February 1999, 183 patients (27.7% of total admissions) were secluded on 306
      occasions. The mean duration of seclusion was 90.3 hours (minimum I hour; maximum
      908 hours). A higher proportion of female patients (60%) was secluded than of
      male patients (25%). Sixty-five percent of the patients were secluded once, 29.5
      percent two to four times, and 5.5 percent more than four times. Suicidal threats
      and self-harm gestures were the reasons for initiating seclusion in 27.4 percent
      of cases. Patients with diagnosed substance-related disorders accounted for 40.8
      percent of all seclusion episodes, whereas those with schizophrenia and related
      psychoses accounted for 28.1 percent. These findings suggest that seclusion
      remains a relatively common intervention in some disturbed patients in a forensic
      setting.

PMID- 11592459
TI  - The phantom expert: unconsented use of an expert's name and/or testimony, as a
      legal strategy.
AB  - The authors explore the forensic, legal, and ethical issues involved in a
      spectrum of attorney practices involving designating experts without notifying
      them. Recommendations are offered for dealing with this unethical practice,
      including exposure of the practice, reportage to bar association ethics
      committees, and continued open discussion and research.

PMID- 11592460
TI  - Boundary violation ethics: some conceptual clarifications.
AB  - The practices of both forensic psychiatry and clinical psychiatry appear to
      require and to use, in boundary-violation discourse, a special way of referring
      to the heightened attention to the ethics of interpersonal exchange. But this
      discourse and the judgments it expresses are each in need of closer scrutiny. A
      variety of factors make the determination of certain actions to be boundary
      violations unclear, including the range of alleged boundary-violating behavior,
      ambiguities in the fundamental metaphor of boundaries violated or transgressed,
      and confusion about the explanatory status of the value judgments boundary
      violation language is used to express. In addition, disputes and disagreements
      regarding boundary-violation judgments require analysis--an analysis undertaken
      in this article through appeal to theories of professional role morality. Noted
      also is the significance of gender in boundary-violation ethics.

PMID- 11592462
TI  - Law and psychiatry: the totalitarian experience.

PMID- 11592461
TI  - Semyon Gluzman and the unraveling of Soviet psychiatry.

PMID- 11592463
TI  - Withholding, seducing, and threatening: a pilot study of further attorney
      pressures on expert witnesses.

PMID- 11592464
TI  - Sexually violent predator II: the sequel.

PMID- 11592465
TI  - Clinical and forensic aspects of postpartum disorders.

PMID- 11592466
TI  - Introduction: the need for a multidimensional and multidisciplinary approach.
AB  - This special issue combines contributions from several disciplines within the
      social sciences on how to understand long-term use or dependency on various kinds
      of psychotropics. It emphasizes the need for a multidisciplinary approach in
      order to understand the complexity of such long-term use. The papers in this
      issue will base their arguments on psychological, sociological, anthropological,
      clinical, and social pharmacy perspectives. Different disciplines focus specially
      on certain topics. For example, psychology can help us to understand what kind of
      mental processes that are involved in the development of long-term tranquillizer
      use. Sociology, anthropology and social pharmacy have a particular contribution
      to make in helping us, in different ways, to understand the social meanings of
      psychotropic drug use.

PMID- 11592467
TI  - Identity, cognitive structure, and long-term tranquillizer use: a
      multidimensional approach.
AB  - The article discusses different theoretical perspectives that are relevant in
      analysing long-term tranquillizer use. The theories mentioned are, e.g.,
      behavioral theory models, cognitive models, humanistic and existential models,
      transpersonal identity models, psychodynamic reasoning, sociological and
      anthropological perspectives. A multidimensional model focusing on the connection
      between identity structure and long-term tranquillizer use is presented. The
      article argues for the use of mixed methodological strategies, e.g., quantitative
      and qualitative methods. The implications of the 'actor-spectator paradox" for
      the analysis of data are also discussed in some detail.

PMID- 11592468
TI  - Experiences of long-term tranquillizer use: a psychodynamic perspective.
AB  - The aim of the article is to analyse narrative descriptions and experiences of
      long-term tranquillizer use. The analysis is based on a Danish in-depth study of
      50 informants with a self-diagnosed dependency on tranquillizers. The theoretical
      analysis is dependent on psychodynamic reasoning. Further, the psychodynamic
      perspective is integrated within a multi-dimensional model that considers
      biological, cognitive, identity, gender and social learning factors. The analysis
      reveals the possibility of achieving a detailed understanding of the dynamic
      processes involved in the development of long-term tranquillizer use. Important
      themes frequently mentioned in the clients' descriptions are traumatic childhood
      experiences, identity problems, life crises in adulthood and difficulties in
      stopping taking psychotropic drugs.

PMID- 11592469
TI  - Long-term users of psychotropic drugs: embodying masculinized stress and
      feminized nerves.
AB  - This article examines long-term users of psychotropic drugs (43 men and 57 women)
      and their views on women's and men's reasons for using these drugs. The data came
      from written statements (N= 56) given on open-ended questions from a survey of
      users and from taped interviews with 10 respondents. Men's accounts expressed a
      notion of men as experiencing external pressures which created "masculinized
      stress." On the one hand, this stress could be handled with alcohol, while, on
      the other hand, the use of psychotropic drugs indicated a loss of men's assumed
      self-regulatory power and autonomy. Women related the reasons for their
      psychotropic drug use to their experience of emotional labor. Nevertheless, they
      did not tend to identify the psychological consequences of their experience as
      related to work. Rather, they labelled these as health consequences--women being
      more "emotional" than men and suffering from "nerves." These lay accounts reflect
      the representations of gender-specific psychological distinctions and the effort
      to construct gender-specific etiologies.

PMID- 11592470
TI  - Evaluation of programs for the treatment of benzodiazepine dependency.
AB  - Programs for the treatment of benzodiazepine dependency differ in a number of
      ways. Their outcome goals, for example, vary. In some of the programs the
      reduction or the elimination of benzodiazepine use is the main objective. In
      others a reduction in anxiety and depression among patients is regarded as much
      more important than decreasing benzodiazepine use. These differences in goals
      make comparative evaluations difficult. Further, the type of clients recruited to
      the programs are often dissimilar. However, it is still possible and valuable to
      make comparative evaluations of the numerous programs. The aims of published
      evaluations differ. Most evaluations are directed towards outcome data. Only in a
      few studies has the aim been to analyze the dynamic treatment process. To achieve
      more reliable and valid evaluations it is necessary to get data which describe
      the process and the results from both the clients' and the therapists'
      perspectives and combining different research strategies.

PMID- 11592471
TI  - Benzodiazepines as a social problem: the case of halcion.
AB  - This paper uses the case study of the crisis surrounding the benzodiazepine
      sleeping tablet Halcion (triazolam). particularly in the UK and US, to assess the
      explanatory value of the developmental model of drugs as a social problem first
      outlined by Gabe and Bury (9). It is argued that the case study supports the
      value of the model's three stage approach of emergence, legitimation and state
      response but that further comparative work needs to be undertaken with prescribed
      drugs other than benzodiazepines in order to substantiate fully the claim that
      the model represents a "natural history" of drugs as a social problem.

PMID- 11592472
TI  - Mass media representations as drug information for patients: the prozac
      phenomenon.
AB  - Results of a 20-year study of mass media representations of antidepressant
      medications and their use are presented. The recent Prozac phenomenon stands out
      as a primary example of media-generated drug information for patients. Various
      forms of mass media are important in providing perceptions of the effects,
      benefits, and safety of these new antidepressant drugs. Clinical research,
      however, suggests that the latest generation of antidepressant medications is no
      more effective in treating depressive symptoms than the first generation,
      tricyclic antidepressants. Yet, these new antidepressants have become the model
      drug not only for treating depression, but also for cosmetic psychopharmacology.

PMID- 11592473
TI  - Balancing diversion control and medical necessity: the case of prescription drugs
      with abuse potential.
AB  - Narcotics and other prescription drugs play a significant and legitimate role in
      medical practice. The illicit use of prescribed medicines, however, remains a
      major problem. This paper examines the effectiveness of two drug diversion
      control programs, multiple copy prescriptions programs (MCPP) and electronic data
      transfer (EDT) systems, and their impact on medical practice. Current evidence
      demonstrates that these programs decrease prescription drug use, with much of the
      decrease due to declines in inappropriate use. MCPPs appear more effective than
      EDT in preventing diversion. More research is needed. however, to assess their
      effects on medical practice, particularly patient quality of care.

PMID- 11592474
TI  - Becoming a problematic consumer of narcotics.
AB  - Based on participant observation studies of problematic consumers of narcotics in
      Stockholm, Sweden, this paper presents a life-history model illuminating why the
      research subjects started using narcotics and continued to do so. The model
      consists of four stages. The first two are initiated before the individual begins
      taking drugs. and lead to the development of a drastically negative self-image.
      The third stage consists of consciously breaching societal norms, thereby
      provoking responses which confirm and consolidate the negative self-image. In the
      fourth stage still more drastic deviant behavior and an increasingly negative
      self-image mutually reinforce each other.

PMID- 11592475
TI  - Toward an integrative approach in the analysis of dependency problems.
AB  - This article takes some preliminary steps towards an integrated analysis of
      dependency problems e.g., long-term tranquillizer use, alcohol dependence,
      problematic use of narcotics. It argues for the need to outline important
      theoretical, epistemological, and methodological prerequisites in the analysis of
      the complex dynamic developmental processes involved in dependency problems. The
      dynamic process leading to dependence can be studied by the aid of an artificial
      science neural network approach in combination with a mixed method strategy
      including a clarification of a combination of different epistemological
      positions. It is intended that the empirical output of this complex strategy will
      provide a starting point for a new theoretical analysis which, in turn, will lead
      to new and more relevant input variables in the neural network approach that will
      help us to extend our knowledge of the dynamic processes leading to dependency.

PMID- 11592476
TI  - Epilogue: drawing together the threads and perspectives on the long-term use of
      psychotropics.
AB  - The aims of the epilogue are to draw together the threads in this issue by
      reviewing some themes presented in the previous chapters and to consider the
      relationship between the perspectives mentioned. The implications of a
      multidimensional perspective for future research, treatment and prevention are
      discussed. It is emphasized that the social sciences have an important part to
      play in helping us understand long-term use of psychotropics. The social sciences
      provide insights of importance for research, treatment and prevention of
      dependency on psychotropics, and also, may help us deal better with these kind of
      problems in the future.

PMID- 11592477
TI  - Species-specific evolution of repeated DNA sequences in great apes.
AB  - DNA sequencing reveals that the genomes of the human, gorilla and chimpanzee
      share more than 98% homology. Comparative chromosome painting and gene mapping
      have demonstrated that only a few rearrangements of a putative ancestral
      mammalian genome occurred during great ape and human evolution. However,
      interspecies representational difference analysis (RDA) of the gorilla between
      human and gorilla revealed gorilla-specific DNA sequences. Cloning and sequencing
      of gorilla-specific DNA sequences indicate that there are repetitive elements.
      Gorilla-specific DNA sequences were mapped by fluorescence in-situ hybridization
      (FISH) to the subcentromeric/centromeric regions of three pairs of gorilla
      submetacentric chromosomes. These sequences could represent either ancient
      sequences that got lost in other species, such as human and orang-utan, or, more
      likely, recent sequences which evolved or originated specifically in the gorilla
      genome.

PMID- 11592478
TI  - Chromosome evolution in the annual killifish genus Cynolebias and mitochondrial
      phylogenetic analysis.
AB  - Extensive chromosome variation involving Robertsonian and non-Robertsonian
      changes were proposed to explain chromosomal evolution within killifishes of the
      aplocheiloid group belonging to the order Cyprinodontiforms. In the present work
      we describe the karyotypes of four Cynolebias species and analyze chromosome
      changes by means of mitochondrial phylogenetic studies, including 10 taxa of this
      genus. Diploid numbers varied from 48 to 44 and the number of chromosome arms
      from 50 to 54. Molecular phylogenetic analyses allow us to corroborate previous
      hypothesis about chromosome evolution in aplocheiloid fishes. The tree topology
      based on a combined dataset of mitochondrial cytochrome b and 12S genes shows
      that recent cladogenetic events within the genus Cynolebias could have occurred
      by allopatric or 'in-situ' differentiation involving chromosomal rearrangements.
      Our analyses of approximately 10% of mitochondrial genome can be helpful in
      determining these recent cladogenetic events but it showed limited phylogenetic
      resolution at intermediate levels of divergence. This can be explained in part by
      the high levels of DNA sequence divergence (ranging from 0.015 to 0.245) detected
      at intrageneric level. Different methodological approaches suggest that
      chromosomal changes in Cynolebias have occurred during their differentiation,
      supporting the hypothesis that the unresolved basal polytomy could be the result
      of rapid speciation events, like a true 'star polytomy'.

PMID- 11592479
TI  - An uncommon condition for a sex chromosome system in Characidae fish.
      Distribution and differentiation of the ZZ/ZW system in Triportheus.
AB  - Triportheus is a neotropical freshwater Characidae fish that has a well
      differentiated ZZ/ZW sex chromosome system. The W chromosome of this genus
      contains a large amount of heterochromatin and is smaller than the Z chromosome.
      This contrasts with other ZW fish systems where the W chromosome is larger in
      size due to increased heterochromatin. All species of Triportheus that have been
      studied cytologically (about 50% of the known species for this genus, from some
      of the major South American hydrographic basins) share this sex chromosome
      system, indicating a probable synapomorphic condition not present in other genera
      of the large Characidae family. However, while the Z chromosome appears to be
      largely conserved, the W chromosome shows a differential evolution with
      morphological differentiations not only among species, but also among populations
      from the same hydrographic basin, and with some species presenting a greater
      homology between the W and the Z chromosomes than others.

PMID- 11592480
TI  - Absence of Z-chromosome inactivation for five genes in male chickens.
AB  - In order to examine if Z-chromosome inactivation, which is analogous to X
      chromosome inactivation in mammals, takes place in male birds having ZZ sex
      chromosomes, five Z-linked genes of chickens which are expressed in both sexes in
      certain tissues were selected: i.e. genes for growth hormone receptor, nicotinic
      acetylcholine receptor beta3, aldolase B, beta1,4-galactosyltransferase I, and
      iron-responsive element-binding protein (also known as cytosolic aconitase).
      Antisense or sense riboprobe was prepared from an intronic sequence of each gene
      and subjected to fluorescence in situ hybridization to nascent transcripts of
      each gene in a nucleus. Each antisense riboprobe hyridized to two spots of
      nascent RNA which corresponded to its gene loci on the two Z chromosomes in a
      majority of nuclei in a tissue of the male. The efficiency of detection of two
      spots per nucleus was comparable to that for the glyceraldehyde-3-phosphate
      dehydrogenase gene, an autosomal housekeeping gene. These results suggest
      strongly that Z-chromosome inactivation, i.e. virtual silence of transcription at
      one of the alleles, does not take place for these five Z-linked genes in male
      chickens.

PMID- 11592481
TI  - Additional locus of rDNA sequence specific to the X chromosome of the liverwort,
      Marchantia polymorpha.
AB  - The molecular cytogenetic organization of 17S ribosomal RNA genes (17S rDNA), a
      part of the 45S rDNA repeat, was investigated on the chromosomes of the liverwort
      Marchantia polymorpha using fluorescence in-situ hybridization (FISH). The
      numbers of 17S rDNA loci visualized in female and male chromosomes were ten and
      nine. respectively. This heterogeneous localization was due to the presence of an
      additional 17S rDNA locus on the X chromosome and its absence on the Y
      chromosome. The signal on the X chromosome covered almost the entire region of
      its long arm. The other nine signals were observed on the same loci of respective
      autosomes in both sexes. Southern hybridization analysis revealed an additional
      band including 17S rDNA exclusively on EcoRI digested female genomic DNA
      supporting the existence of an additional 17S rDNA locus on the X chromosome.

PMID- 11592482
TI  - Efficient in-vitro transfer of a 60-Mb mammalian artificial chromosome into
      murine and hamster cells using cationic lipids and dendrimers.
AB  - Non-integrating artificial chromosomes represent a potentially promising approach
      to ex-vivo and in-vivo gene therapy applications. These large vectors require an
      efficient means for delivery to target cells. We have evaluated a panel of twenty
      one commercially available transfection agents for their ability to mediate the
      in-vitro transfer of a 60-Mb murine artificial chromosome consisting of mouse
      major satellite DNA and a payload including a marker gene (hygromycin B) and a
      reporter gene (lacZ). A rapid screening procedure utilizing iododeoxyuridine
      incorporated artificial chromosomes facilitated the assessment of different
      transfection conditions. The results were confirmed by cytogenetic analysis of
      positively transfected clones. By transfecting both hamster lung fibroblast cells
      (V79-4) and murine connective tissue cells [L-M(TK-)], the best results were
      obtained using either Superfect (cationic dendrimer) or LipofectAMINE 2000
      (cationic lipid) with protocols adapted for metaphase chromosome preparation.
      Transfection efficiencies of 10(-4)-10(-2) (0.01-1%) were routinely observed, and
      recipient cells were able to maintain expression of the reporter gene over the
      total length of the experiment. This represents a significant advance over our
      previous attempts at mass-transfection of artificial chromosomes using microcell
      fusion, where we routinely achieved efficiencies at least two orders of
      magnitudes less than reported here. These data are particularly noteworthy given
      that lipid-mediated gene transfer typically involves transfecting millions of
      plasmids (1 microg of DNA from a 5 kb plasmid is approximately 1.2 x 10(11)
      copies) to each cell whereas the much larger artificial chromosomes comprise only
      a one-to-one ratio, yet achieve transfection efficiencies of (10(-2)-10(-1)),
      that is, comparable to our results. These data suggest that artificial
      chromosomes containing therapeutic genes can be successfully delivered to target
      cells in vitro using well-established transfection agents.

PMID- 11592483
TI  - Histone H3 phosphorylation of mammalian chromosomes.
AB  - Inferences about the role and location of phosphorylated histone H3 are derived
      primarily from biochemical studies. A few direct observations at chromosome level
      have shown that phosphorylation begins at the site of heterochromatin and spreads
      throughout the chromosome. However, a comparative study of chromosomes of mouse
      (L929 cells), Chinese hamster (CHO 9 cells) and the Indian muntjac (male cells)
      reveals some distinguishable details among mammalian species. Whereas the L929
      cells exhibit the typical pattern of phosphorylation at the region of centromeric
      heterochromatin associated with the active centromere, the heterochromatin blocks
      associated with the inactive centromeres also show label of about equivalent
      intensity. Throughout the cell cycle, heterochromatin exhibits sharper (denser)
      and better defined label than does euchromatin which expresses somewhat diffuse
      label. The centromere constriction on biarmed chromosomes, originating in
      Robertsonian translocations, appears phosphorylated in some, if not all
      chromosomes. A similar situation was found for the CHO 9 cells indicating that
      phosphorylation does include the region in which H3 is supposedly replaced by
      CENP-A. An interesting feature of the CHO cell line was the dense label at and
      near the telomeres; this feature was not observed in either the mouse or the
      Indian muntjac. The centromere regions of the Indian muntjac chromosomes showed
      three sites of label in the multicentric X chromosome and two each on chromosome
      pair number 1 and Y2; the sites coinciding with the reaction sites of
      antikinetochore antibodies. Also, the X and Y, chromosomes of Indian muntjac show
      intense phosphorylation at the sites of secondary constrictions. The chromosomes
      of all three species were phosphorylated throughout the cell cycle. As the
      chromosomes started to decondense during anaphase, heavy phosphorylation was
      observed in the form of discontinuous beaded structures indicating partial
      despiralization of the chromosome. Interestingly, when cells had completed
      karyokinesis and resolved into two independent nuclei, the phosphorylation was
      observed at the midbody. At this stage, the cytoplasm appeared to be again
      phosphorylated.

PMID- 11592484
TI  - The 5S rDNA of mussels Mytilus galloprovincialis and M. edulis: sequence
      variation and chromosomal location.
AB  - The 5S ribosomal DNA of the mussels Mytilus galloprovincialis and M. edulis was
      amplified by PCR using contiguous primers. The most general 5S rDNA amplification
      pattern consisted of several products in both mussels. Two main PCR products of
      about 250 bp and 760 bp were cloned and sequenced, revealing two classes of 5S
      rDNA units. These were characterized as containing an identical coding region of
      119 bp but with highly divergent spacers. Clones of each unit type exhibited
      minimal differences except those of the large unit of M. edulis. The sequences
      analysed of the two mussels possess the same coding region and only six fixed
      base changes on the spacers. FISH, carried out with specific probes, consistently
      showed hybridization signals on the largest metacentric pair (two differentiated
      sites) and with variable frequency on two other metacentric pairs (one site on
      each pair). Differences in the 5S rDNA distribution between both mussels were not
      found. In M. edulis, chromosomes carrying 18S-28S rDNA were also identified by
      FISH. These correspond to two submetacentric-subtelocentric pairs, as was
      previously reported in M. galloprovincialis, demonstrating that the two rDNA
      multigene families are located on different chromosome pairs in these mussels.

PMID- 11592485
TI  - Transcriptional activity of an inversion split NOR in barley (Hordeum vulgare
      L.).
AB  - The transcriptional activity of NORs in a new structural mutant of barley (PK-88
      4) was studied based on the positive reaction of NORs of metaphase chromosomes
      with AgNO3 and the number and size of silver-stained nucleoli in somatic
      interphase cells and meiocytes. PK-88-4 proved to contain a pericentric inversion
      that split NOR 7 into two unequal parts residing in the opposite arms of the
      reconstructed chromosome 7(5). This chromosomal rearrangement enables testing of
      intrachromosomal suppression of NORs and provides insight into the mechanisms of
      intraspecific nucleolar dominance. Both parts of the split NOR proved to be
      transcriptionally active, and are not subject to intrachromosomal nucleolar
      dominance. Thus, translocation-induced intraspecific nucleolar dominance is
      probably the result of interaction of NOR6 and NOR7 or other genetic factors
      located on the NOR-bearing chromosomes 6(6H) and 7(5H).

PMID- 11592486
TI  - Chromosomal localization of the genes encoding SCNN1A, BTG1, IFNG and MAOA on
      chicken chromosome 1 by fluorescence in-situ hybridization.

PMID- 11592487
TI  - Implantation of bacteria from human pulpal necrosis and translocation from root
      canals in gnotobiotic mice.
AB  - The aim of this study was to determine whether microorganisms recovered from
      infected human root canals were able to survive and translocate to a local lymph
      node when experimentally inoculated into the root canal system of germ-free mice.
      The microorganisms isolated from two patients with pulpal necrosis were
      inoculated in two groups of experimental animals; group I (Gemella morbillorum)
      and group II (Bifidobacterium adolescentis, Fusobacterium nucleatum, and
      Clostridium butyricum). G. morbillorum showed the highest frequency of
      colonization and translocation to the draining lymph node. In group II only F.
      nucleatum and C. butyricum colonized and translocated when inoculated in tri
      association. When the bacteria from group II were inoculated in monoinfection all
      three species colonized the root canal of germ-free mice and translocated to the
      draining lymph node, but with different frequencies. We conclude that selective
      mechanisms occur in which some bacterial species are fit to survive, multiply,
      and translocate in the germ-free mouse model.

PMID- 11592488
TI  - Radiographic evaluation of periradicular repair after endodontic treatment of
      dog's teeth with induced periradicular periodontitis.
AB  - Eighty-four root canals of premolars from six dogs were left open for 7 days, and
      then sealed and followed for 45 days until periradicular periodontitis developed.
      The root canals were then treated endodontically using 5.25% sodium hypochlorite
      as the irrigating solution. After instrumentation, all root canals were filled
      with a calcium hydroxide-based antibacterial dressing (Calen PMCC or Calasept)
      that was left in place for 30 days. After this period the root canals were filled
      with gutta-percha cones and a root canal sealer (Sealapex or AH Plus)--group I:
      Calen PMCC + Sealapex; group II: Calasept + Sealapex; group III: Calen PMCC + AH
      Plus; and group IV: Calasept + AH Plus. Periapical radiographs of the teeth were
      made after root canal filling and after 90, 180, 270, and 360 days. Radiographic
      images were digitalized by scanning, and the Mocha program was used to measure
      the periapical lesions. Analysis showed that the lesions of groups I to III were
      statistically similar reduction in size, whereas group IV had a smaller reduction
      in lesion size (p < 0.05).

PMID- 11592489
TI  - In vitro evaluation of a calcium phosphate cement root canal filler/sealer.
AB  - An in vitro dye leakage study was performed to compare the apical leakage of a
      fill with injectable calcium phosphate cement (CPC) filler/sealer and a master
      silver cone with leakage from a fill of Sealapex sealer and laterally condensed
      gutta-percha. Ten instrumented, extracted, single-rooted human teeth were
      obturated with either laterally condensed gutta-percha and Sealapex as the sealer
      or with a single master cone and the CPC paste sealer. Additional teeth were
      included in the study to serve as controls. The teeth were placed in 1% poly-R
      dye solution (pH 7.0) for 5 days. After the teeth were longitudinally sectioned
      apical leakage of dye was measured. There were no significant differences between
      the CPC and Sealapex groups. The single cone CPC procedure provided an adequate
      apical seal against dye penetration. Should retreatment become necessary the
      single cone may be removed to provide access for instrumentation.

PMID- 11592490
TI  - Susceptibilities of Enterococcus faecalis biofilms to some antimicrobial
      medications.
AB  - Enterococcus faecalis has been suggested to be an important etiological agent in
      endodontic failures. The purpose of this study was to evaluate the effectiveness
      of chlorhexidine- or antibiotics-based medications in eliminating E. faecalis
      biofilms. One-day and three-day biofilms of E. faecalis were induced on cellulose
      nitrate membrane filters. Each biofilm-containing membrane was thoroughly covered
      with 1 ml of the test medications and incubated for 1 day at 37 degrees C.
      Treated biofilms were then aseptically transferred to vials containing a
      neutralizing agent in saline solution and vortexed. Suspensions were 10-fold
      diluted, seeded onto Mitis salivarius agar plates, and the colony-forming units
      counted after 48 h of incubation. There were significant differences between the
      formulations tested. The association of clindamycin with metronidazole
      significantly reduced the number of cells in 1-day biofilms. However of all
      medications tested, only 2% chlorhexidine-containing medications were able to
      thoroughly eliminate most of both 1-day and 3-day E. faecalis biofilms.

PMID- 11592491
TI  - Evaluation of functional GABA(B) receptors in dental pulp.
AB  - Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that is elevated
      in inflamed human dental pulp. Because GABA agonists are antihyperalgesic in
      other tissue, it is possible that GABA agonists have similar effects in dental
      pulp assuming that this tissue contains GABA receptors. We tested the hypothesis
      that dental pulp contains functional GABA(B) receptors using a GTPgamma35S
      binding assay. This is a functional assay because GTPgamma35S will be bound to
      cell membranes only when activation of metabotropic receptors has lead to binding
      and activation of their associated G(alpha)-proteins via release of GDP and
      binding of the GTPgamma35S. Baclofen, a GABA(B) agonist, evoked GTPgamma35S
      binding in both human and bovine dental pulp. This was mediated by the GABA(B)
      receptor because it was blocked by the selective antagonist phaclofen in both
      tissues. The presence of GABA and its receptor, GABA(B), suggests that this
      system may be relevant in the production or management of endodontic pain.

PMID- 11592492
TI  - The continuous locking suture technique.
AB  - The continuous locking suture technique is described for use in endodontic
      surgery. The technique is an effective way to close Ochsenbein-Luebke flaps. The
      importance of the assistant's role is described. The technique's advantages and
      disadvantages are discussed.

PMID- 11592493
TI  - A comparison of mesial molar root canal preparations using two engine-driven
      instruments and the balanced-force technique.
AB  - The purpose of this study was to compare the effects of two engine-driven, nickel
      titanium instrument systems with hand files in the final shape of slight and
      moderately curved canals. A total of 72 mesial roots of extracted human
      mandibular molars were divided into three groups: ProFile .04 taper, Pow-R rotary
      systems, and Flex-R hand-filing technique. The roots were mounted and cross
      sectioned at two different horizontal levels using a modified Bramante technique.
      Pre- and postinstrumented cross-sectional roots were imaged, recorded, and
      computer analyzed. Results showed that, at the middle third, in almost all
      groups, there was a tendency of cutting more toward the mesial side with only one
      exception: Pow-R cut more to the distal side (danger zone) (p < 0.02). At the
      apical third, Flex-R (p < 0.03) and ProFile (0.001) transported to the mesial
      side (danger zone) when the curvature increased. When the three techniques were
      compared analyzing each side and considering the two groups of curvature, at the
      middle third in the moderately curved-canal group, Flex-R cut statistically more
      than Pow-R toward the lingual side. The other comparisons showed no statistically
      significant difference. When the techniques were compared in relation with the
      degree of curvature, in the apical third, ProFile .04 cut statistically more
      toward the mesial side in the moderately curved canal group than in the slightly
      curved canal group. The other comparisons showed no statistically significant
      difference. Canal preparation time was shorter with hand instrumentation (p <
      .05) in a few instances.

PMID- 11592496
TI  - Implants versus the natural tooth--stand up for what we know is right.

PMID- 11592494
TI  - Removal of fractured posts using ultrasonic vibration: an in vivo study.
AB  - The purpose of this study was to determine the effectiveness of ultrasonic
      vibration in the removal of fractured posts from teeth under true clinical
      conditions. Thirty patients (16 men and 14 women with a mean age of 51 yr, SD
      13.13) had ultrasonic vibration applied to the side of a fractured post fragment
      after creation of a small gutter around the fragment. A piezoelectric ultrasonic
      scaler was used to apply the vibration for two 15-s periods and then 30-s periods
      until the post fragment became loose. There was a significant correlation (r =
      0.52, p = 0.003) between the cemented length of post fragment (mean length 3.8
      mm, SD 1.39) and the time of ultrasonic vibration application (mean time 2.05
      min, SD 1.62), but the correlation between post diameter and ultrasonic time did
      not reach statistical significance (r = 0.35, p = 0.059). The mean ultrasonic
      time was approximately 25% of that found in previous studies on post removal from
      extracted teeth probably because of suboptimal cementation of posts in the
      clinical situation.

PMID- 11592497
TI  - SW-163C and E, novel antitumor depsipeptides produced by Streptomyces sp. I.
      Taxonomy, fermentation, isolation and biological activities.
AB  - Novel depsipeptides, SW-163C and E were isolated from the culture broth of an
      actinomycete strain. The producing organism, designated as SNA15896, was
      identified as a member of Streptomyces from its morphological and cultural
      characteristics. SW-163C and E exhibited potent antitumor activities against
      various tumor cell lines in vitro and against murine leukemia P388 in vivo. The
      compounds also showed antimicrobial activities.

PMID- 11592498
TI  - SW-163C and E, novel antitumor depsipeptides produced by Streptomyces sp. II.
      Structure elucidation.
AB  - SW-163C and E are novel antitumor antibiotics, which belong to quinomycin family,
      isolated from the culture broth of Streptomyces sp. SNA15896. These compounds
      were determined to be cyclic depsipeptides having 3-hydroxyquinaldic acid as a
      chromophore and a sulfur-containing intramolecular cross linkage through various
      spectroscopic analyses.

PMID- 11592499
TI  - TMC-205 a new transcriptional up-regulator of SV40 promoter produced by an
      unidentified fungus. Fermentation, isolation, physico-chemical properties,
      structural determination and biological activities.
AB  - A new transcriptional up-regulator designated TMC-205 was discovered from the
      fermentation broth of an unidentified fungal strain TC 1630 by using an SV40
      promoter-luciferase reporter assay. Based on spectroscopic analyses, its
      structure was determined to be (E)-6-(3-methyl-1,3-butadienyl)- H-indole-3
      carboxylic acid. Expression of the luciferase activity was activated ca. 2-, 4-,
      and 6-fold by 1, 10, and 100 microM TMC-205, respectively. TMC-205 activated the
      transcriptional activity in a manner dependent on the presence of the enhancer
      element of SV40 in its promoter region.

PMID- 11592500
TI  - Cladospolide D, a new 12-membered macrolide antibiotic produced by Cladosporium
      sp. FT-0012.
AB  - A new antibiotic termed cladospolide D was isolated along with the known
      cladospolides A and B from the fermentation broth of Cladosporium sp. FT-0012 by
      solvent extraction, ODS column chromatography and preparative HPLC. The structure
      of cladospolide D was deduced to be (E)-2-dodecen-5-hydroxy-11-olide-4-one.
      Cladospolide D showed antifungal activity against Pyricularia oryzae and Mucor
      racemosus.

PMID- 11592501
TI  - Effects of aflastatin A, an inhibitor of aflatoxin production, on aflatoxin
      biosynthetic pathway and glucose metabolism in Aspergillus parasiticus.
AB  - Aflastatin A inhibits aflatoxin production by Aspergillus parasiticus via an
      unknown mechanism. We found that aflastatin A clearly inhibited production of
      norsolorinic acid, an early biosynthetic intermediate of aflatoxin, at a
      concentration of 0.25 microg/ml. Reverse-transcriptase polymerase chain reaction
      (RT-PCR), and real-time quantitative PCR (TaqMan PCR) experiments indicated that
      the transcription of genes encoding aflatoxin biosynthetic enzymes (pksA, ver-1,
      and omtA) and a gene encoding a regulatory protein for expression of the
      biosynthetic enzymes (aflR) were significantly reduced by the addition of
      aflastatin A. We also found that aflastatin A elevated the glucose consumption
      and ethanol accumulation by A. parasiticus, and repressed transcription of genes
      involved in ethanol utilization. These results suggest that aflastatin A inhibits
      a very early step in aflatoxin biosynthesis prior to the transcription of aflR
      and can influence glucose metabolism in the fungus.

PMID- 11592503
TI  - Synthesis and antibacterial activity of the tricyclic ketolides TE-802 and its
      analogs.
AB  - The novel 6-O-methyl tricyclic ketolides TE-802 and its analogs were synthesized
      by two successive cyclization reactions, 11,12-cyclic carbamate formation by
      intramolecular Michael addition and 9,11-diazaheptene ring construction by
      intramolecular dehydration reaction. These new tricyclic ketolides exhibited good
      in vitro antibacterial activity against not only erythromycin-susceptible strains
      but also erythromycin-resistant Staphylococcus aureus and Streptococcus
      pneumoniae, which are problematic pathogens of nosocomial and community-acquired
      respiratory tract infections, respectively.

PMID- 11592502
TI  - Potent antimalarial activities of polyether antibiotic, X-206.
AB  - In the course of our screening program to discover antimalarial antibiotics,
      which are active against drug resistant Plasmodium falciparum in vitro and
      rodents infected with P. berghei in vivo, from the culture broth of
      microorganisms, we found a selective and potent active substance produced by an
      actinomycete strain K99-0413. It was identified as a known polyether antibiotic,
      X-206. We also compared the in vitro antimalarial activities and cytotoxicities
      of 12 known polyethers with X-206. Among them, X-206 showed the most selective
      and potent inhibitory effect against both drug resistant and sensitive strains of
      P. falciparum. Comparison of biological activities and ion-affinities of the
      above antibiotics suggests that monovalent cations play an important biological
      role for the intracellular growth of P. falciparum in parasitized erythrocytes.
      Moreover, X-206 showed potent in vivo antimalarial activity on the rodent model,
      though the therapeutic window was narrow compared with its selective toxicity in
      vitro. These observations are the first report of antimalarial activity of X-206.

PMID- 11592504
TI  - New bioactive cyclopentenone derivatives as inhibitors of the IL-6 dependent
      signal transduction.

PMID- 11592505
TI  - Inhibition of ribonucleotide reductase activity by IC202C.

PMID- 11592506
TI  - Obstetrical brachial plexus palsy: an analysis of 105 cases.
AB  - Obstetrical brachial plexus palsy (OBPP) remains a dramatic consequence after
      complicated childbirth. An increasing number of methods are being developed for
      the physical therapy and the early repair of the nerve lesions in OBPP, including
      neuroma excision and nerve grafting, neurolysis and neurotization. Secondary
      deformities of the shoulder, forearm, and hand can be reconstructed using soft
      tissue and skeletal procedures. In this article we analyze our approach to 105
      patients to obtain optimal functional outcome in patients with OBPP.

PMID- 11592507
TI  - Assessment of protein-energy malnutrition in children with chronic arthritis.
AB  - Protein-energy malnutrition (PEM) has been estimated to occur in 10 to 50% of
      children with juvenile chronic arthritis (JCA). Thirty-eight children with JCA
      were evaluated and their nutritional status determined, and they were compared
      with 23 healthy sex and age-matched children as controls. A standardized, 9
      parameter comprehensive nutritional assessment profile was used. The simple
      anthropometric measurements, height and weight for age, were abnormal in 30% and
      27% of the patients, respectively. A detailed evaluation revealed that 71% had
      abnormal somatic protein stores, and that they also had significantly low levels
      of visceral protein stores, when compared to their healthy peers. The results
      were consistent with the fact that inflammation put the JCA patients at
      significant risk for developing complicated malnutrition and it might result in
      PEM without any obvious signs of malnutrition. A nutritional screening test would
      be very useful in detecting early PEM in children with chronic arthritis.

PMID- 11592508
TI  - Fiberoptic flexible bronchoscopy via the laryngeal mask airway in children.
AB  - The laryngeal mask airway (LMA) is a new device for controlling the airway during
      many procedures. Aside from its use in different kinds of surgical procedures,
      fiberoptic flexible bronchoscopy can also be performed easily with this mask in
      children under sedation. This procedure was performed via LMA in 36 children
      (aged 2-16 years) who suffered from different kinds of respiratory diseases and
      were seen at Hacettepe University Ihsan Dogramaci Children's Hospital, Pediatric
      Chest Disease Unit, during a seven-month period. The procedure was performed with
      success and no complications occurred. To the best of our knowledge, this is the
      first report from Turkey on flexible bronchoscopic evaluation via LMA in children
      with different kinds of respiratory diseases. We suggest that this technique can
      be used safely.

PMID- 11592509
TI  - Preliminary pediatric transesophageal echocardiography experiences.
AB  - With transesophageal echocardiography (TEE), a new echocardiographic window is
      obtained which enables cardiologists to explore the heart from the esophagus and
      stomach. However, the procedure, when first undertaken, may present certain
      difficulties for the cardiologist in interpreting the anatomical findings and
      approaching a diagnosis. We thus convey our first experiences and results of TEE
      in 107 pediatric patients. Transesophageal echocardiography (TEE) was performed
      in 107 pediatric patients at our institution between December 1998-February 2001,
      using the standard techniques and following the standard criteria suggested by
      the American heart Association. The mean age of 54 male (50.5%) and 53 female
      (49.5%) patients was 7.8 years. Intubation difficulty was experienced in four
      cases. In one case, while drawing the transducer back from the esophagus, it
      kinked at the hypopharynx. None of the cases had major hemorrhage or esophageal
      rupture, and only a few cases had minor pharyngeal injuries or hemorrhages. We
      used TEE in detecting vegetations in patients with possible endocarditis, and
      evaluating the prosthetic valves and abnormal pulmonary venous return. We also
      used TEE to clarify preooperative anatomical details, postoperative complications
      and residual defects of complex congenital cardiac anomalies. Transcattheter
      closure of 47 secundum atrial septal defects (ASD)'s and a muscular ventricular
      septal defect (VSD) (both during patient selection and during the procedure) were
      accomplished under TEE guidance. As the pediatric cardiologists gain more
      experience in performing TEE, this technique will have a wider and more effective
      use in the pediatric population.

PMID- 11592510
TI  - Overdiagnosis of pneumonia in children.
AB  - The aim of this study was to reevaluate patients diagnosed as pneumonia in our
      outpatient clinic in an effort to determine whether these patients really had
      pneumonia and needed antibiotic therapy. Over a 14-month period, 119 children who
      were diagnosed as pneumonia were prospectively evaluated. In order to find a
      relationship, specificity and sensitivity were defined. The diagnosis of
      pneumonia was ruled out in 48 of the 119 (40%) patient included. An incorrect
      diagnosis of pneumonia was made in 40% of cases and antibiotics were prescribed
      unnecessarily in 85%. Tachypnea, which had a specificity of 99% and sensitivity
      of 61%, was the most important criteria in diagnosing pneumonia. We believe that
      children who present with cough only do not always need antibiotic treatment.
      Tachypnea and auscultation findings are important criteria for diagnosing and
      treating pneumonia.

PMID- 11592511
TI  - Screening for tuberculosis in a primary school in Ankara.
AB  - Tuberculosis is still an important health problem in developing countries. A
      screening program was conducted upon learning that one of the teachers of a
      primary school in Ankara was diagnosed to have active pulmonary tuberculosis. A
      total of 341 students in the same building with the index case were screened for
      tuberculosis. There were 109 students with positive tuberculin test reaction. A
      higher ratio of tuberculin test positivity among the students of the teacher with
      active tuberculosis versus students vaccinated with BCG one year previously
      according to the routine vaccination program was determined. Isoniazid
      prophylaxis was given to the students with positive tuberculin test. The study
      shows the importance of an urgent work-up of index cases and their environment to
      prevent the spread of tuberculosis.

PMID- 11592512
TI  - Serum lipid peroxidation levels in small-for-gestational-age babies.
AB  - The levels of lipid peroxidation in sera of asymmetric small-for-gestational-age
      (SGA) babies at the second hour of life were investigated. Lipid peroxidation
      levels, measured as malondialdehyde (MDA), were 3.3 +/- 1.1 and 3.9 +/- 1.2
      mmol/L in SGA and appropriate-for-gestational age (AGA) groups, respectively. The
      difference was not significant (p>0.05). This result may indicate that free
      radical scavengers are sufficient in SGA babies.

PMID- 11592513
TI  - Complications of the two major operations of Hirschsprung's disease: a single
      center experience.
AB  - This study was designed to determine and compare the results of the Duhamel and
      Swenson procedures. The hospital records of patients who had undergone the
      Swenson or Duhamel operation over a 17-year period were reviewed and the patients
      were contacted for a final evaluation. The early and late complications of these
      operations were defined and compared. It was determined that the Swenson
      operation had been performed in 138 patients and the Duhamel in 59. Among the
      various complications, such as wound infection, dehiscence, anastomotic leak,
      adhesive intestinal obstruction, pelvic abscess, intraabdominal abscess, mucosal
      prolapsus, anastomotic stricture and fistulas, only the anastomotic stricture
      showed significantly higher percentages in patients who had undergone the Swenson
      procedure. When urinary incontinence, enterocolitis, soiling and constipation
      were considered, there was no significant difference between these two groups.
      There was one death in the Swenson group and none in the Duhamel group. The
      authors suggest the Duhamel operation as a simpler and safer method for the
      treatment of Hirschsprung's disease.

PMID- 11592514
TI  - Socioeconomically advantaged infants attending a university well-child clinic in
      Ankara: are they breast-feeding optimally?
AB  - This longitudinal observational study aimed to determine the rates of initiation,
      duration and correlates of breast-feeding by mothers living in a
      socioeconomically advantaged urban environment in Turkey. Healthy, term infants
      born at Ankara University Faculty of Medicine Hospital who would be brought to
      the well-child clinic regularly for at least 12 months were enrolled. Data on
      feeding practices were obtained at the 1st, 2nd, 3rd, 4th, 5th, 6th, 9th and 12th
      month well child care visits. Breast-feeding outcome was categorized based on
      recommendations by the World Health Organization (WHO). The majority of the 295
      participating mothers were older than 20 years, high school graduates, and lived
      in apartment housing, and 54.6% were employed. The rates of breast-feeding were
      97.9%, 90.1%, 76.9% and 36.9% at 1, 4, 6 and 12 months, respectively, and rates
      of exclusive breast-feeding were 89.8%, 59.3% and 2.0% at 1, 4 and 6 months,
      respectively. At 6 months 69.8% of infants were receiving cow's milk and by 12
      months only 23.4% of the infants had been breast-fed according to WHO
      recommendations. Neither gender; birth weight of infant; age, education, parity,
      previous breast-feeding experience of mother; nor the status of living as
      extended versus nuclear family were related to breast-feeding outcome. Mothers
      who were working (RR: 3.89, 95% CI: 1.42-10.65) and those who had less than 4
      months postpartum leave from work (RR: 4.20, 95% CI: 2.16-8.17) were more likely
      to not breast-feed optimally. The results of this study indicate that even where
      breast-feeding is normative behavior, it may not be optimally practiced, leading
      to potentially detrimental nutrition for infants. Promotion of breast-feeding
      even in advantaged urban populations is needed.

PMID- 11592515
TI  - The impact of pre- and perinatal factors on attention-deficit and disruptive
      behavior disorders.
AB  - Diagnosis of attention-deficit and disruptive behavior disorders defines a group
      of disorders which have common properties. This group consists of attention
      deficit hyperactivity disorder, conduct disorder and oppositional defiant
      disorder. In order to differentiate these disorders, which share similar
      properties, it is important to verify the existing differences. In this respect,
      differences between and distribution of perinatal factors in these three
      disorders were investigated. The study was conducted in the Child Psychiatry and
      Pediatric Neurology Departments over a 20-month period. Two hundred and seventy
      children out of 1,556 attendant with various complaints were diagnosed to have
      one of the following disorders: 121 had attention-deficit hyperactivity disorder,
      50 had oppositional defiant disorder and 99 had conduct disorder. The prenatal
      and perinatal data of the patients were evaluated retrospectively by a
      neonatologist. With regard to the investigated parameters, none showed any
      significant difference between the three groups when compared. The three
      disorders, which share many similarities in terms of the symptoms, also show
      similarities in terms of perinatal factors. Since we did not find any study
      similar in design, our results, although statistically not significant, are
      discussed in light of the little data available.

PMID- 11592516
TI  - Gaucher disease type I: analysis of two cases with thalassemic facies and
      pulmonary arteriovenous fistulas.
AB  - Here we report two unusual patients with Gaucher disease type I. Both girls
      admitted with hepatosplenomegaly, growth retardation, and anemia at four and 2.5
      years of age, and Gaucher cells were seen on bone marrow aspirates. Thalassemic
      face was first noted at 8 and 11 years of age, respectively, with frontal bossing
      and maxillary hypertrophia. Although they had unconjugated hyperbilirubinemia,
      high reticulocytes, polychromasia, and normoblasts on peripheral smear, other
      laboratory tests for hemolytic disease were negative. Radiological examination
      revealed typical bone involvement of Gaucher disease, as well as costal
      enlargement and obliteration of paranasal sinuses, the latter two reported in
      hemolytic diseases. Cyanosis, digital clubbing and recurrent lung infections led
      to contrast echocardiography that revealed diffuse pulmonary arteriovenous
      shunting in both. Diagnosis was confirmed by low leukocyte beta glucosidase
      levels and mutations N370S7/L444P (Case 1) and N370S/? (Case 2). These features,
      all reported for the first time, may show a new clinical course in Gaucher
      disease.

PMID- 11592517
TI  - Abetalipoproteinemia: a case report.
AB  - Abetalipoproteinemia is a rare autosomal recessive disorder characterized by
      steatorrhea, poor weight gain, acanthocytosis and retinitis pigmentosa. Here we
      peresent a six-month-old patient with abetaliporoteinemia. He had a history of
      chronic diarrhea from the first month of life. He was cachectic and his motor
      development was delayed. Microscopic examination of the stool revealed fat. Mild
      anemia with reticulocytosis, acanthocytosis, low triglyceride, low cholesterol,
      low-density lipoprotein, high-density lipoprotein, and apolipoprotein A and B
      were detected. Ophthalmological examination was normal. Peroral jejunal capsule
      biopsy revealed normal villi and significant lipid deposition in the cytoplasm of
      affected cells. The patient was given large doses of vitamins E and A.

PMID- 11592518
TI  - A case of Netherton's syndrome with cerebral infarction.
AB  - Netherton's syndrome, a rare congenital disease of childhood, is characterized by
      variable cutaneous erythematous eruptions with different manifestations. A five
      year-old boy, who presented with ichthyosis linearis circumflexa, atopic
      manifestations and pili torti, had spastic hemiparesia due to cerebral
      infarction. Netherton's syndrome can easily be misdiagnosed as Leiner's disease,
      generalized psoriasis or nonbullous congenital ichthyosiform erythroderma,
      especially in the neonatal period, because of its nonspecific clinical and
      histological features. Pediatricians should consider this syndrome in the
      differential diagnosis of the generalized erythematous skin disorders of
      childhood associated with various abnormalities.

PMID- 11592519
TI  - Complex partial seizure mimicking psychotic reaction in an adolescent.
AB  - A previously healthy 15-year-old boy initially diagnosed to have acute psychotic
      reaction had a history of a single generalized seizure and prolonged amnestic
      states of varying intensity and duration. An ictal electroencephalogram (EEG)
      showed bitemporal ictal discharges starting from the left side. Carbamazepine was
      started. A magnetic resonance imaging (MRI) obtained on the 10th day of the
      antiepileptic therapy showed increased signal intensity on the T2 weighted
      images. The patient's memory function markedly improved during 10 months' follow
      up with antiepileptic treatment, although he described brief attacks of
      dizziness. A repeat MRI examination showed normal findings. The amnesticstates
      were thought to be due to frequent complex partial seizures, and transient MRI
      changes to hippocampal edema. This case illustrates the importance of epileptic
      disorders in the differential diagnosis of psychiatric conditions.

PMID- 11592520
TI  - Megakaryocyte emperipolesis in a child with chronic neutropenia: an unusual
      coexistence.
AB  - The term emperipolesis defines the temporary presence of one cell within
      another's cytoplasm. In clinical use, megakaryocyte emperipolesis is the
      penetration of hematopoietic cells into the cytoplasm of megakaryocytes. The
      pathophysiological significance of megakaryocyte emperipolesis is uncertain. It
      has been described in association with neoplastic disorders, and in a few
      instances in idiopathic thrombocytopenic purpura, iron deficiency anemia,
      bleeding, and during the administration of recombinant human granulocyte colony
      stimulating factor. However, megakaryocyte emperipolesis in a patient with
      chronic neutropenia has not been reported. In the current report, emperipolesis
      of hematopoietic cells within megakaryocytes in a boy with chronic neutropenia is
      described and the possible mechanisms are discussed.

PMID- 11592521
TI  - Anomalous origin of one pulmonary artery branch from ascending aorta ("so-called
      hemitruncus"): report of an additional case treated surgically.
AB  - The aortic origin of one pulmonary artery branch, so-called hemitruncus, is a
      rare congenital anomaly with poor prognosis. In this report, an additional
      patient is presented. The patient, a 60-day-old male infant with the right
      pulmonary artery originating from the ascending aorta was operated successfully.
      Postoperative catheterization demonstrated normal flow to the right lung and
      pulmonary artery pressure decreased to normal level.

PMID- 11592522
TI  - Noncompaction of the right ventricle following Senning repair.
AB  - A three-year-old boy presented with generalized edema, respiratory distress,
      prominent right ventricular impulse and hepatosplenomegaly. He had undergone
      Senning repair at one year of age. On his echocardiography, there were numerous
      prominent trabeculations and deep intertrabecular recesses measuring
      approximately 5 mm in depth along the free wall and right ventricular apex.
      Echogenicity of the endocardial surface was increased suggesting a fibrotic
      process in progress. Intertrabecular recesses were observed to be filling from
      the ventricle by color Doppler which is consistent with noncompaction. Various
      semilunar valve obstructions were shown to be responsible for the persistence of
      deep endomyocardial spaces surrounded by exeggerated hypertrophy of the
      trabeculae. This report presents the echocardiographic findings of right
      ventricular cardiomyopathy associated with dextroposition of the great arteries
      following Senning operation resembling noncompaction. Thus, this rare entity
      needs to be clarified regarding morphological criteria in distinction from other
      cardiomyopathies.

PMID- 11592523
TI  - A case of osteopetrosis with pelvic ectopic spleen: an unusual association.
AB  - A three-month-old girl was admitted to the hospital with a history of pallor. On
      physical examination, the liver was enlarged and a solid mass was palpated in the
      left abdomen. Laboratory evaluation revealed anemia and thrombocytopenia. Bone
      marrow was hypocellular with reduced number of megakaryocytes. Radiographic
      findings and scintigraphic study of the long bones were consistant with
      osteopetrosis. In the imaging studies, including ultrasonography, computerized
      tomography, magnetic resonance imaging and scintigraphic study, an ectopic spleen
      expanded into the bony pelvis was observed. We report here unique case of
      infantile osteopetrosis associated with pelvic ectopic spleen.

PMID- 11592524
TI  - Thoracoschisis associated with diaphragmatic hernia in a 31-week-old stillbirth.
AB  - Thoracoschisis is a very rare congenital anomaly and is frequently found with
      other congenital defects the of limbs and the abdominal wall as a part of limb
      body wall complex (LBWC). Early vascular disruption, amnion rupture and intrinsic
      embryonic maldevelopment are related to the pathogenesis of this complex. We
      present a case of thoracoschisis with ipsilateral diaphragmatic hernia. This case
      had none of the associated anomalies which are seen in LBWC. By ultrasonography
      performed at 31 weeks' gestation the fetus was misdiagnosed as gastroschisis. In
      this report we discuss the pathogenetic mechanism of LBWC and our case.

PMID- 11592525
TI  - Bilateral subpleural ectopic brain tissue in a 23-week-old fetus.
AB  - Bilateral lesions were seen in the subpleural region in a 23-week-old aborted
      male fetus. This fetus was not macerated and showed no central nervous system
      abnormality on physical examination and vertebral magnetic resonance imaging
      (MRI). Postmortem examination revealed bilateral, paravertebral, subpleural,
      circumscribed, yellowish-white, fluent lesions 2.5 x 1 x 1 cm in size. These
      lesions were localized on the upper part of both lungs and there was no other
      internal malformation. Histological examination of lesions showed adult neurones
      and well-differentiated neural tissue with white and gray matter, choroid plexus,
      ependymal structures and, rarely, some peripheral neural cells in addition to
      immature neuroectodermal cells. These cells were more mature than those in the
      brain tissue.

PMID- 11592526
TI  - Apoptosis and anti-apoptosis signalling in glaucomatous retinopathy.
AB  - PURPOSE: Recent studies in the post-mortem human retina have suggested that
      apoptosis contributes to retinal ganglion cell (RGC) loss in glaucoma. If
      apoptosis contributes significantly to glaucomatous RGC loss, and if the specific
      apoptosis signalling pathways for glaucomatous apoptosis can be determined,
      agents that interrupt or oppose the signalling have the potential to slow the
      progression of glaucoma. METHODS: Recent data in animal models indicate that
      mitochondrially-dependent apoptosis contributes to RGC loss in glaucoma.
      Mitochondrially-dependent apoptosis involves proteins like BAX that increase
      mitochondrial membrane permeability and promote apoptosis and proteins like BCL-2
      that decrease mitochondrial membrane permeability and reduce apoptosis. New
      protein synthesis induced by the alpha-2 agonist, brimonidine, prevents decreases
      in the levels of BCL-2 and thereby reduces mitochondrially-dependent apoptosis.
      CONCLUSIONS: Brimonidine appears to maintain BCL-2 levels by supporting the
      activity of an intrinsic anti-apoptosis signalling system that involves
      phosphorylation of protein kinase B. Phosphorylated protein kinase B appears to
      counteract the apoptosis signalling mechanisms which operate in glaucomatous
      retina.

PMID- 11592527
TI  - Animal and culture models of glaucoma for studying neuroprotection.
AB  - PURPOSE: Neuroprotection aims to treat nervous system disease by maintaining the
      health and function of neurons. The final proof of the neuroprotective strategy
      relies on randomized, controlled clinical trials, but the choice of which agents
      to study for these trials depends on studies in the laboratory using culture and
      animal models. Most culture models for studying ocular neuroprotection use
      retinal cells, and a range of mechanisms can be studied in culture, e.g. axotomy
      and serum or growth factor deprivation. METHODS: A variety of animal models are
      available for studying neuroprotection as possible therapy for glaucomatous optic
      neuropathy. Those most closely related to glaucoma are probably associated with
      moderate elevation of the intraocular pressure to levels similar to those seen in
      patients with untreated glaucomatous optic neuropathy. CONCLUSIONS: Care should
      be taken when applying the results of these models to humans, and there is no
      single criterion for deciding which culture or animal model is most relevant to
      the clinical situation. The most important feature is whether the model's results
      correlate with clinical results, and this information will only become available
      over time, as randomized clinical trials are completed.

PMID- 11592528
TI  - Alpha-2 adrenergic receptor agonists are neuroprotective in experimental models
      of glaucoma.
AB  - PURPOSE: The glaucomas are characterized by chronic progressive ganglion cell
      loss over many years. A drug with neuroprotective activity should increase the
      resistance of retinal ganglion cells (RGC) to chronic stress or injury and
      therefore enhance survival. Brimonidine is a highly selective and potent alpha-2
      adrenergic receptor agonist, which lowers intra-ocular pressure (IOP) and is
      neuroprotective. Immunohistochemistry data have shown that the specific receptor
      targets, the alpha-2 receptors, are located in the inner retina. METHODS:
      Brimonidine 0.1 mg/kg given intraperitoneally promoted RGC survival compared with
      vehicle using the optic nerve crush model even when administered up to 24 hours
      before injury. Using the chronic ocular hypertensive rat model, brimonidine 1
      mg/kg/day (with osmotic pump) significantly prevented the loss of RGCs when
      compared with vehicle or timolol. This ability was due to the neuroprotective
      action of brimonidine, since it did not affect IOP. In addition, brimonidine 0.1
      mg/day reached concentrations in the retina of Sprague-Dawley rats within 30
      minutes of injection, which was sufficient to activate the alpha-2 receptor (> or
      = 2 nM) and maintained these concentrations for 6 hours. CONCLUSIONS: Having
      demonstrated that: a. the specific receptor target of brimonidine is located in
      the retina, which is important for optic neuroprotection, b. the agent shows
      neuroprotective ability in animal models, c. pharmacological concentrations of
      the drug can be reached in the retina, clinical trial has been initiated to
      determine whether brimonidine is neuroprotective in patients with nonarteritic
      ischaemic optic neuropathy.

PMID- 11592529
TI  - Brimonidine's neuroprotective effects against transient ischaemia-induced retinal
      ganglion cell death.
AB  - PURPOSE: Brimonidine is a lowering pressure agent currently used in glaucoma.
      This chronic degenerative condition is characterised by neuronal death, and an
      agent which offers neuroprotection may slow down or impede the progression of
      neuronal cell death. METHODS: The effects of brimonidine (BMD) on the short- and
      long-term survival of retinal ganglion cells (RGCs) after transient retinal
      ischaemia are reported here using a rat model. The fluorescent tracer Fluorogold
      (FG) was applied to both superior colliculi to retrogradely label RGCs. A ninety
      minute period of ischaemia was induced and densities of surviving RGCs were
      estimated over time by counting FG-labelled RGCs in 12 standard regions of each
      retina. RESULTS: Seven days after inducing transient ischaemia, there was loss of
      approximately half of the RGC population. Topical pre-treatment with 0.1% or 0.5%
      BMD prevented ischaemia-induced RGC death. CONCLUSIONS: These results indicate
      that optimal neuroprotective effects against the early loss of RGCs are seen with
      0.1% or 0.5% BMD. Ischaemia-induced RGC loss continued between day 7 and day 21
      in the vehicle treated groups and amounted to approximately 25% of the RGC
      population. Topical pre-treatment with 0.1% or 0.5% BMD was also effective in
      reducing the slow loss of RGCs.

PMID- 11592530
TI  - Electrophysiological approaches for early detection of glaucoma.
AB  - PURPOSE: While elevated intraocular pressure (IOP) is a major risk factor for
      glaucoma, only about 1% of patients with 25 mmHg develop the condition each year.
      Since a sizeable proportion of the ganglion cells are already lost when the
      visual field losses are apparent, the aim is to identify patients with elevated
      IOP in whom glaucoma damage is incipient before visual field changes occur.
      METHODS: This report concerns early diagnosis of glaucoma with
      electrophysiological techniques, rather than with monitoring the disease using
      various available psychophysical and morphological methods. Visual
      electrophysiology offers a wide range of tools to assess function layer-by-layer
      along the visual pathway. Their clinical value for early detection of glaucoma
      will be discussed. The pattern electroretinogram (PERG), a direct functional
      indicator of retinal ganglion cell function, is markedly affected by glaucoma,
      and in longitudinal studies the PERG correctly indicated eyes at risk before
      manifest glaucoma occurred. CONCLUSIONS: Consequently, this report will
      concentrate on the PERG. Less proven, but promising measures like the "photopic
      negative response", the motion visually evoked potential (VEP) and the multifocal
      VEP will also be touched upon.

PMID- 11592531
TI  - Measuring structural changes in the optic nerve head and retinal nerve fibre
      layer.
AB  - PURPOSE: Assessing structural changes in the optic nerve is fundamental to the
      diagnosis and follow-up of glaucoma. Many clinical decisions are based on the
      determination of stability or non-stability of glaucomatous damage. Retinal nerve
      fibre layer (RNFL) and optic disc photographs are very useful in clinics but
      their assessment is based on subjective evaluation. METHODS: Confocal scanning
      laser ophthalmoscope and confocal scanning laser polarimetry are available and
      allow objective and quantitative analysis of the optic nerve. These instruments
      are currently being assessed for their use in glaucoma follow-up. CONCLUSIONS:
      This article summarises their advantages and limitations in performing the
      difficult task of detecting progression or changes over time.

PMID- 11592532
TI  - Evaluation of glaucomatous visual field loss with locally condensed grids using
      fundus-oriented perimetry (FOP).
AB  - PURPOSE: We compared detection rates of glaucomatous visual field defects (VFDs)
      between a conventional rectangular stimulus grid and locally condensed test point
      arrangements in morphologically suspicious regions. METHODS: Humphrey Field
      Analyzer model 630 (HFA I, program 30-2 with a rectangular 6 degrees x 6 degrees
      grid) was used as the conventional perimetric method. Individual local test-point
      condensation was realized by fundus-oriented perimetry (FOP) on the Tuebingen
      Computer Campimeter (TCC). RESULTS: Of a total of 66 glaucoma patients, or
      suspected sufferers, 23 showed normal findings and 27 showed pathological
      findings with both methods. In 15 cases we found normal visual fields in HFA 30
      2, whereas FOP revealed early glaucomatous functional damage. Only one case
      showed pathological HFA results, while FOP was normal. Detection rates of VFDs
      significantly differed between the two methods (p < 0.001; sign test).
      CONCLUSIONS: FOP, using individually condensed test grids, significantly
      increases detection rates of glaucomatous VFDs in morphologically suspicuous
      areas compared with a conventional HFA 30-2 technique using equidistant
      rectangular (6 degrees x 6 degrees) test point arrangements.

PMID- 11592533
TI  - Beta-adrenergic antagonists in the treatment of glaucoma.
AB  - PURPOSE: Beta-blockers have been used since the late 1970's as 'first-choice' in
      the treatment for glaucoma. Since the introduction of new molecules in clinical
      routine, the current role of beta-blockers in glaucoma therapy has been
      rediscussed. In particular, concerns have been raised regarding their actual
      safety profile. METHODS: This review will focus on the latest advances on the
      efficacy and safety profiles of non-selective beta-blockers. CONCLUSIONS: The
      data provided will help to trace a more appropriate role for beta-blockers in
      glaucoma therapy.

PMID- 11592534
TI  - Influence of topical brimonidine on visual field in glaucoma.
AB  - PURPOSE: We evaluated the efficacy of topical brimonidine in visual field
      preservation and/or improvement in eyes undergoing controlled glaucoma. METHODS:
      Seventy eyes of patients were trained with two different visual field test
      strategies: The Octopus Tendency Oriented Perimetry (TOP) G1 and the Frequency
      Doubling Technology (FDT) 30 degrees. Following 2-4 months of brimonidine
      treatment, there were significant improvements in visual field, as assessed using
      the TOP G1 strategy (p = 0.003). The FDT 30 degrees test revealed no
      statistically significant differences. CONCLUSIONS: These data support the
      results of other studies, which indicate that brimonidine may increase mean
      sensitivity in visual field tests. Since it is known that the control of
      intraocular pressure does not fully protect glaucomatous eyes from visual field
      loss, it is possible that the neuroprotective qualities of brimonidine may
      contribute to visual field preservation in glaucomatous eyes.

PMID- 11592535
TI  - Neuroprotection as a treatment for glaucoma: pharmacological and immunological
      approaches.
AB  - PURPOSE: Primary open-angle glaucoma is a chronic, progressive optic neuropathy
      associated with a gradual decline in visual functions, which may lead to
      blindness. METHODS: In most cases, the optic neuropathy is associated with
      increased intraocular pressure. However, it is now generally accepted, that
      normalization of pressure, although necessary, is often not sufficient as a
      remedial measure. This is because of the existence of additional risk factors,
      some of which emerge as a consequence of the initial damage. This situation is
      reminiscent of the response to a traumatic axonal insult: some of the damage is
      immediate and is caused by the insult itself, while some is secondary and is
      caused by a deficiency of growth-supportive factors as well as by toxic factors
      derived from the damaged tissue. Accordingly, we have suggested that glaucoma may
      be viewed as a neurodegenerative disease and consequently is amenable to any
      therapeutic intervention applicable to these diseases. CONCLUSIONS: There is
      evidence that neuroprotection can be achieved both pharmacologically and
      immunologically. Pharmacological intervention (e.g. by using selective alpha-2
      adrenergic receptor agonists) neutralizes some of the effects of the nerve
      derived toxic factors and possibly increases the ability of the remaining healthy
      neurons, at any given time, to cope with the stressful conditions. Immunological
      intervention boosts the body's own repair mechanisms for counteracting the
      toxicity of physiological compounds acting as stress signals.

PMID- 11592536
TI  - Brimonidine (Alphagan): a clinical profile four years after launch.
AB  - The early information on the clinical efficacy, safety, and tolerability of
      brimonidine 0.2% were obtained from studies that compared brimonidine monotherapy
      with timolol and betaxolol. These studies showed its intra-ocular pressure
      lowering efficacy to be comparable with timolol and superior to betaxolol. The
      data from the timolol studies showed consistent results after four years. These
      findings have been confirmed by additional studies in the clinical setting. More
      recently, several clinical trials have been completed investigating the role of
      brimonidine as adjunctive medication to beta-blockers and as replacement therapy
      to other intraocular pressure lowering compounds. When added to beta-blockers,
      brimonidine is superior to dorzolamide, similar in efficacy but better tolerated
      than pilocarpine, and more predictable than latanoprost. Data from replacement
      studies have indicated that there may be advantages in replacing rather than
      adding medications in the treatment of glaucoma.

PMID- 11592537
TI  - Personal preferences of obstetricians towards childbirth.
AB  - Our objective was to determine obstetricians' personal choices in relation to
      modes of delivery and long-term outcomes. A structured confidential survey was
      mailed out to all Australian and New Zealand Fellows, Members, and Australian
      Trainees with The Australian and New Zealand Journal of Obstetrics and
      Gynaecology November 1999 edition. The response rate overall was 26% (478).
      Eleven per cent (54) chose to have an elective Caesarean section (ECS) in the
      absence of any clinical indication. The most common reason for this was fear of
      faecal and urinary incontinence (82%). Two-thirds (318) were agreeable to
      patients requesting an ECS in this same setting. Twenty-six per cent said they
      would choose ECS if the estimated fetal weight (EFW) was > 4000 g which more than
      doubled to 55% (261) if EFW was > 4500 g. Ventouse delivery was the most popular
      method of assisted rotational delivery at 45% (214) followed closely by
      Keilland's forceps at 40% (189). Caesarean section (CS) was chosen by only 14%
      (65) in this scenario. ECS was the preferred method for breech delivery at 38%
      (181) followed by trial of breech delivery at 23% (109). Thirty-two per cent
      (154) of respondents would attempt external cephalic version prior to deciding
      mode of delivery. Respondents felt the most important factors for postnatal
      incontinence included: antenatal incontinence (64%), length of second stage > one
      hour (50%), forceps delivery (46%), and EFW > 4000 g at term (44%).

PMID- 11592538
TI  - Team midwife care: maternal and infant outcomes.
AB  - The aim of this study was to add additional information on intervention rates and
      maternal and infant outcomes of team midwife care to previous reports which have
      suggested this model of care can be associated with a reduction in medical
      interventions during labour and birth with no statistically significant influence
      on maternal and infant outcomes. The study was designed as a randomised
      controlled trial, with 495 women randomised to team midwife care being compared
      to 505 women randomsed to standard care. The study revealed no statistical
      differences between team midwife care and standard care in medical interventions,
      maternal health and infant health. These findings suggest that team midwifery as
      it is practised in this study is a safe alternative for women.

PMID- 11592539
TI  - The management of extremely premature infants and the perceptions of viability
      and parental counselling practices of Australian obstetricians.
AB  - The attitudes of Australian obstetricians to the resuscitation of extremely
      premature infants are reported. A structured questionnaire including questions
      regarding antenatal parent counselling, resuscitation practices, survival rates
      and personal attitudes about life support was distributed to obstetricians
      working in Australian hospitals with a Level 3 nursery Eighty-nine (48% response
      rate) replies were received from 12 units located in seven major cities.
      Obstetricians are more likely to discuss resuscitation with prospective parents
      with increasing gestation with a major shift occurring at 23-24 weeks' gestation.
      They strive for consensus with parents regarding resuscitation options and they
      act upon the opinion of both the prospective parents and their paediatric
      colleagues. Threat of litigation rarely influences the decision to limit
      resuscitation of an extremely preterm infant. Obstetricians may underestimate the
      prognosis for extremely preterm infants. The data presented offer useful insights
      into current attitudes and practice of tertiary hospital obstetricians.

PMID- 11592540
TI  - Antenatal counselling, resuscitation practices and attitudes among Australian
      neonatologists towards life support in extreme prematurity.
AB  - A questionnaire survey of Australian neonatologists was conducted to ascertain
      their antenatal counselling and resuscitation practices, and attitudes towards
      life support in the extremely preterm infant. This study showed that in antenatal
      parental counselling, whether a paediatrician was given the opportunity to
      participate depends on the gestation at the time of the threatened preterm
      delivery The counselling employed almost invariably covered mortality and
      morbidity. The obstetrician's opinion was considered to be of utmost importance.
      Both financial and moral obligations were found to be of little importance in
      counselling and resuscitation. Only one-third of institutions had guidelines for
      limiting resuscitation. The onus remained on the neonatologists concerning which
      infant to resuscitate, and the level of the resuscitation to be conducted. In
      Australia, resuscitation at birth was restricted to infants of 23 weeks'
      gestation or above, and neonatologists did not believe the legal system has a
      role to play in limiting or mandating resuscitation of extremely preterm infants.
      Neither were they concerned with the threat of litigation when they decide to
      limit resuscitation. The majority of neonatologists agreed with their
      institution's approach to life support in extremely preterm infants. One grey
      area was the question of withholding assisted feeding in an infant for which the
      decision to withdraw life support has been made. Australia lacked a current
      consensus policy on selective non-treatment. The establishment of national
      guidelines would be helpful to aid Australian obstetricians and neonatologists in
      their clinical practice.

PMID- 11592541
TI  - Relationship between birthweight and repeated courses of antenatal
      corticosteroids.
AB  - A retrospective study was conducted in a university teaching hospital to review
      the association between birthweight and the number of courses of antenatal
      corticosteroids received in 236 singleton pregnancies. Those pregnancies
      complicated with pregnancy-induced hypertension, preeclampsia, diabetes mellitus
      and intrauterine growth restriction were excluded. The results showed that the
      birthweight ratio (calculated as the baby's birthweight divided by the median
      birthweight for that gestational age) was negatively correlated with the number
      of courses of corticosteroids received. Further, exposure to four or more courses
      of antenatal corticosteroids was associated with a significant reduction in
      birthweight ratio and a three-fold increase in the risk of being small-for-dates
      compared to those exposed to one to three courses.

PMID- 11592542
TI  - Screening for gestational diabetes mellitus: can we be more efficient?
AB  - In a retrospective review of 471 patients screened for gestational diabetes
      mellitus (GDM) in a community laboratory, we compared 50 g polycose screening
      test results with those of the 75 g oral glucose tolerance test (GTT). The rate
      of GDM diagnosis was compared using criteria promulgated by the New Zealand
      Society for Study of Diabetes (NZSSD), Australian Diabetes in Pregnancy Society
      (ADIPS) and World Health Organisation (WHO). In those with borderline screening
      results (7.8-8 mmol/L) the rate of GDM diagnosis using NZSSD criteria was low
      (2.8%) compared with higher screening test results (> or = 8.1 mmol/L), where the
      rate was 7.4%. Corresponding rates were 7.5% and 13.5% using ADIPS criteria and
      5.6% and 12.4% using WHO criteria. The predictive value of a positive 50 g
      screening test is therefore low, especially for the higher New Zealand criteria.
      In women with borderline screening results no subject had a two-hour plasma
      glucose of 9.0 mmol/L or more on oral GTT. This suggests that the current
      screening cut-off of 7.8 mmol/L might be raised to 8.1 mmol/L, resulting in a 25%
      reduction in the number of glucose tolerance tests. Those with significant risk
      factors such as macrosomia, however, still warrant greater clinical suspicion and
      closer follow-up.

PMID- 11592543
TI  - Comparison of transvaginal ultrasound, saline infusion sonography and
      hysteroscopy to investigate postmenopausal bleeding and unscheduled bleeding on
      HRT.
AB  - A study was conducted to compare transvaginal ultrasound (TVS), saline infusion
      sonography (SIS) and outpatient hysteroscopy for examining the uterine cavity in
      women with postmenopausal bleeding and unscheduled bleeding on hormone
      replacement therapy (HRT). Fourty Subjects agreed to undergo TVS, SIS and
      hysteroscopy in addition to endometrial sampling. The abnormalities detected by
      each imaging method were recorded together with the discomfort (visual analogue
      scale). Thirty women completed all three imaging procedures. In 18 cases TVS
      suggested an abnormal cavity. SIS and hysteroscopy were of similar efficacy in
      clarifying the nature of this, and confirmed an abnormality in 12 cases (40%).
      TVS was significantly less painful than the other procedures (p < 0.001). SIS and
      hysteroscopy were associated with pain scores similar to endometrial sampling.
      These findings justify the need for a large randomised trial of TVS, SIS,
      hysteroscopy and endometrial sampling, in order to develop the most appropriate
      strategy for investigating postmenopausal bleeding and unscheduled bleeding on
      HRT.

PMID- 11592544
TI  - Ten-year review of hysterectomy morbidity and mortality: can we change direction?
AB  - The medical records of all women who underwent hysterectomy for benign disease
      performed between 1986 and 1995 were reviewed to ascertain the incidence of
      morbidity and mortality of abdominal, vaginal, and laparoscopically assisted
      vaginal hysterectomy at a university teaching hospital. A total of 1940
      hysterectomies were performed during this period; 74% of hysterectomies were
      performed abdominally, 24% vaginally and 2% were laparoscopically assisted. In
      80% of the patients uterine leiomyomas, adenomyosis, dysfunctional uterine
      bleeding or uterine prolapse were the indications for hysterectomy The overall
      complication rate was 44% for abdominal hysterectomy (AH) and 27.3% for vaginal
      hysterectomy (VH). An unintended major surgical procedure was required in 3% and
      1% of women undergoing AH and VH respectively The rate of return to the operating
      room for haemostasis was 0.6% for AH and 0.2% for VH. The AH group was four times
      more likely than the VH group to require surgical intervention (36% versus 9%) at
      readmission. Vaginal hysterectomy was associated with a lower febrile morbidity
      and minor complication rate. Prophylactic antibiotics reduced the febrile
      morbidity for VH and AH by 50% (Student's t-test, p = 0.02) and 40% (Student's t
      test, p < 0.001) respectively The overall mortality rate was 1.5 per 1000.

PMID- 11592545
TI  - Factors influencing the choice of hysterectomy.
AB  - A retrospective review of women undergoing hysterectomy between May 1998 and
      April 2000 was performed. Multiple logistic regression analysis was used to
      identify factors influencing the choice of hysterectomy performed. Two
      independent factors, the surgeons' expertise and the concomitant adnexal surgery,
      had a strong influence on the decision-making process regarding type of
      hysterectomy Generalist gynaecologists tended to perform either an abdominal
      hysterectomy (AH) or a vaginal hysterectomy (VH) while non-generalist
      gynaecologists were more likely to perform laparoscopic hysterectomy (LH).
      Patients undergoing a hysterectomy along with adnexal surgery had a far greater
      chance of undergoing either an AH or a LH as opposed to a VH. In addition,
      patients who had bigger uterus were more likely to undergo an AH versus a VH as
      compared to those with a small uterus. Patients aged 50 or older had more chance
      of undergoing a VH than a LH.

PMID- 11592546
TI  - Total laparoscopic hysterectomy with laparosonic coagulating shears: a
      retrospective report of 200 consecutive cases.
AB  - Despite 10 years of intensive education and training in Australia only around 14%
      of hysterectomies are performed with laparoscopic assistance. In particular total
      laparoscopic hysterectomy (TLH) has a poor penetration rate because of perceived
      technical difficulties that include instrumentation, prolonged operating times
      and an increase in complications. We present a series of 200 consecutive cases of
      TLH with very good results and propose that because of the many advantages that
      this technique offers that it should become the standard procedure for benign
      uterine disease.

PMID- 11592547
TI  - Laparoscopic assisted Doderlein hysterectomy: initial experience in a provincial
      Australian centre.
AB  - Despite the theoretical advantages that laparoscopic hysterectomy techniques
      offer, this is not a commonly performed operation in Australia. The
      laparoscopically assisted Doderlein hysterectomy is a technique that offers
      significant advantages in speed, ease of performance, and low cost. We describe
      our technique and results of the first 36 cases performed for a range of clinical
      indications and uterine weights, using widely available and non-disposable
      equipment. Operating time (including adjunctive operations) varied from 48 to 165
      minutes and no significant complications were encountered.

PMID- 11592548
TI  - The advantages of microlaparoscopic left upper quadrant entry in selected
      patients.
AB  - We describe a series of cases where microlaparoscopic left upper quadrant (LUQ)
      entry was used as the primary peritoneal entry site in patients considered
      unsuitable for initial port placement through the umbilicus. Microlaparoscopic
      LUQ entry is becoming a standard technique in gynaecological laparoscopic surgery
      and appears to provide a safe alternative entry site in selected patients.

PMID- 11592549
TI  - Is the irritable bladder associated with anterior compartment relaxation? A
      critical look at the 'integral theory of pelvic floor dysfunction'.
AB  - The 'integral theory of pelvic floor dysfunction', first proposed by Petros and
      Ulmsten in 1990, claims that anterior vaginal wall relaxation is associated with
      symptoms of urgency, frequency, nocturia and urge incontinence. A retrospective
      study was designed to test this hypothesis. Imaging data and urodynamic reports
      from 272 women suffering from symptoms of lower urinary tract dysfunction were
      evaluated. Opening of the retrovesical angle, bladder neck descent, urethral
      rotation and descent of a cystocele during Valsalva were used to quantify
      anterior vaginal wall laxity. None of the tested parameters were associated with
      symptoms and signs of detrusor overactivity On the contrary, patients with higher
      grades of urethral and bladder descent were less likely to suffer from nocturia
      and urge incontinence and were less likely to have sensory urgency and detrusor
      instability diagnosed on urodynamic testing. The findings of this study therefore
      do not support this hypothesis of the 'integral theory'.

PMID- 11592550
TI  - Variation in cervical cancer screening by region, socio-economic, migrant and
      indigenous status in women in New South Wales.
AB  - The purpose of this study was to estimate the extent of association of cervical
      screening in NSW women with socio-economic status (SES), rurality, and
      proportions of non-English speaking background (NESB) and Indigenous status. Data
      on women who had at least one Pap test over two years (January 1998-December
      1999) were obtained from the NSW Pap test Register. Each local government area
      (LGA) was allocated to categories of population proportions of NESB and
      Indigenous status, a rurality classification based on population density and
      remoteness, and to an SES quintile. The odds ratios (OR) of having a Pap test
      were estimated and confounding adjusted by multiple logistic regression analysis.
      Implied Pap test rates in urban NESB and in rural Indigenous women were estimated
      from the modelled estimates. The adjusted OR for a Pap test in large rural
      centres (1.14) was significantly higher than those for metropolitan or capital
      city residents (0.9 and 1.0 respectively). Adjusted OR for a Pap test in other
      rural centres (0.73) and other remote areas (0.64) were significantly lower than
      those for metropolitan or capital city residents. In urban populations the lowest
      OR were in areas with both low SES and high proportion of NESB. The lowest OR for
      Pap screening in rural populations occurred in the most remote areas with the
      highest proportion of Indigenous women. For urban NESB women the biennial Pap
      test rate was estimated as 50%, and for rural Indigenous women 29%, compared with
      the NSW average of 59%.

PMID- 11592551
TI  - Oestrogen, glycogen and vaginal candidiasis.
AB  - Our aim was to relate vaginal candidiasis to vaginal oestrogenisation. First, the
      incidence was determined (subjected to chi-square analysis) of vaginal Candida
      albicans infection in 339 consecutive dermogynaecology clinic patients aged 55
      years and over, of whom 142 were using and 197 were not using oestrogen. Second,
      the ability of Candida species to utilise glycogen as a sole nutrient source was
      studied by performing assimilation tests using yeast nitrogen broth as a basal
      medium. infection on initial presentation compared with 4% in the cohort not
      using oestrogen (p < 0.001). All 34 isolates of C. albicans assimilated glycogen.
      Twenty-six non-albicans species of Candida tested did not assimilate glycogen. In
      this study of postmenopausal women, there was a highly significant relationship
      between the usage of oestrogen and the occurrence of C. albicans infection. The
      production of glycogen by oestrogen stimulated epithelial maturation provides an
      attractive substrate for C. albicans.

PMID- 11592552
TI  - Methadone and the pregnant user: a matter for careful clinical consideration.
AB  - The practice of placing all pregnant heroin users on methadone as the treatment
      of choice needs to be questioned. While it may be suitable for those who
      stabilise their illicit heroin use at or shortly after conception, its
      suitability for those who show little movement away from regular heroin use and
      its associated lifestyle is more circumspect. Neonates of women who continue
      heroin use throughout pregnancy are likely to be below birthweight and/or
      premature. As a consequence, they are in a less than optimal condition to cope
      with the additional assault caused by prescribed methadone such as neonatal
      withdrawal. This may help explain why the relative risk of neonatal mortality in
      women who continue illicit heroin use during pregnancy and are prescribed
      methadone, is greater than for those who continue to use heroin but are not
      prescribed methadone. Clinicians must take the time of maternal presentation and
      the likelihood of continued maternal heroin use into consideration when
      determining who is suitable for methadone and whether a reduced level of
      methadone will suffice. A number of different clinical scenarios are identified
      and possible management strategies discussed. The need to develop innovative
      services appropriate for pregnant women who continue regular heroin use, and for
      well-designed studies that define best practice for the management of these women
      is evident.

PMID- 11592553
TI  - Oestrogen therapy in the management of vesicovaginal fistula.

PMID- 11592554
TI  - Delayed presentation of uterine perforation and haemorrhagic shock 10 days after
      surgical termination of pregnancy.

PMID- 11592555
TI  - A case of intramural pregnancy: the importance of differentiation from fibroid
      uterus.

PMID- 11592556
TI  - Fetal congenital complete heart block: prophylaxis with intravenous gammaglobulin
      and treatment with dexamethasone.
AB  - We report a case of complete fetal heart block in a 35-year-old Chinese woman
      known to be positive for anti-SSA/Ro and anti-SSB/La antibodies. She had fetal
      hydrops leading to intrauterine death in her first pregnancy Prophylactic
      intravenous immunoglobulin, given at 14 and 18 weeks' gestation, as well as oral
      dexamethasone, commenced at 24 weeks' gestation, allowed continuation of the
      pregnancy until 34 completed weeks of gestation. An external pacemaker was
      inserted in the baby on the first day of life. Two-and-a-half months later, a
      permanent pacemaker was inserted.

PMID- 11592557
TI  - Amniotic fluid embolism during Caesarean section under spinal anaesthesia. Is
      sympathetic blockade a risk factor?

PMID- 11592558
TI  - Term viable abdominal pregnancy: a case report and review.

PMID- 11592559
TI  - Failed conservative management of cervical pregnancy despite falling beta-HCG.

PMID- 11592560
TI  - Sheehan's syndrome--acute presentation with hyponatraemia and headache.

PMID- 11592561
TI  - Malignant mixed Mullerian tumour of the cervix treated with concurrent
      chemoradiation.
AB  - Malignant mixed Mullerian tumours of the cervix are very uncommon. Of the 26
      cases reported in the literature only 8 consist of homologous sarcoma with
      squamous cell carcinoma. Historically, treatment has been with radiation or
      surgery or a combination of both. We describe a locally advanced case treated
      with concurrent chemoradiation.

PMID- 11592562
TI  - The length of time it takes to deliver a baby by emergency Caesarean section.

PMID- 11592563
TI  - Doping with growth hormone.
AB  - Triggered by the Olympic games in Sydney last year, many articles in the press
      suggested that recombinant human growth hormone (hGH) is one of the most popular
      performance enhancing drugs used by athletes. However, any hard facts on hGH
      abuse were provided by Australian customs officers--and not by laboratory
      assessment. The lack of an official test for hGH doping together with the
      widespread rumours on its tremendous beneficial effects seem to make this
      compound attractive for athletes. From a scientific point of view, there are two
      major questions about this issue: First, as there is no controlled study
      demonstrating a profound effect of hGH administration on workload capacity in
      healthy adults, why do athletes use hGH? Second, how could the application of a
      substance naturally occurring in the human body be detected? Both aspects are
      discussed in this article.

PMID- 11592564
TI  - Intrauterine diabetic environment confers risks for type 2 diabetes mellitus and
      obesity in the offspring, in addition to genetic susceptibility.
AB  - Numerous studies have reported that offspring whose mothers had type 2 diabetes
      mellitus (DM) are more likely to develop type 2 DM, impaired glucose tolerance,
      and obesity at an early age than offspring whose fathers had DM. Exposure to the
      diabetic intrauterine environment has been shown to be an important risk factor
      for all these conditions. To what extent transmission of type 2 DM from mother to
      offspring is the effect of genetic inheritance and to what extent it is the long
      term consequence of exposure to maternal hyperglycemia is still uncertain. There
      are, of course, interactions between the diabetic intrauterine environment and
      genetics. Several data in experimental animals as well as in humans suggest,
      however, that exposure of the fetus to the mother's DM confers a risk for type 2
      DM and obesity that is above any genetically transmitted susceptibility. In the
      Pima Indian population much of the increase in childhood type 2 DM can be
      attributed to the diabetic intrauterine environment. This suggests that intensive
      glucose control during pregnancy might have extended beneficial effects,
      contributing to a decrease in the prevalence of childhood type 2 DM.

PMID- 11592565
TI  - Variable presentation of X-linked adrenal hypoplasia congenita.
AB  - We present a family with X-linked adrenal hypoplasia congenita (AHC) due to a
      truncation mutation in the DAX1 gene. The three patient reports demonstrate
      variable clinical and biochemical features at presentation. They presented with
      adrenal crises at 3 years, 4 weeks, and 3 weeks. Mineralocorticoid deficiency
      preceded glucocorticoid deficiency in patient 3 and an early ultrasound indicated
      normal sized adrenal tissue. Genetic analysis showed that potential female
      carriers were unaffected.

PMID- 11592566
TI  - Sustained benefits of growth hormone on body composition, fat utilization,
      physical strength and agility, and growth in Prader-Willi syndrome are dose
      dependent.
AB  - BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS)
      are accompanied by abnormal body composition resembling a growth hormone (GH)
      deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion,
      suggesting a possible therapeutic role for GH treatment. While recent studies
      have demonstrated short-term benefits of treatment with GH, a critical question
      is whether beneficial changes persist or wane with prolonged therapy, and whether
      these effects on body composition are dose-dependent as seen in adult GH
      deficiency. OBJECTIVES AND METHODS: After 24 months of GH theapy at a dose of 1
      mg/m2/day ("standard dose"), the effects of 12 additional months of GH treatment
      at varying doses (0.3-1.5 mg/m2/day) on growth, body composition, strength and
      agility, pulmonary function, resting energy expenditure (REE), and fat
      utilization were assessed in 46 children with PWS. Percent body fat, lean muscle
      mass, and bone mineral density (BMD) were measured by dual X-ray absorptiometry
      (DXA). Indirect calorimetry was used to determine REE and to calculate
      respiratory quotient (RQ). RESULTS: During months 24-36 of GH therapy, further
      changes in body composition (decrease in fat mass, and increase in lean body
      mass), growth velocity, and REE occurred with standard and higher-dose GH therapy
      (1.5 mg/m2/day), but not with lower dose GH (0.3 mg/m2/day). Prior improvements
      in BMD, and strength and agility, which occurred during the initial 24 months,
      were sustained during the additional 12 months (to 36 months) regardless of dose.
      CONCLUSIONS: Salutary and sustained GH-induced changes in growth, body
      composition, and physical function in children with PWS require GH doses of >0.3
      mg/m2/day. Conversely, BMD increased during the additional 12 months of therapy
      regardless of GH dose. Lower doses of GH, effective in improving body composition
      in adults with GHD, do not appear to be effective in children with PWS.

PMID- 11592567
TI  - Insufficient adrenarche in patients with combined pituitary hormone deficiency
      caused by a PROP-1 gene defect.
AB  - Adrenarche was evaluated in five patients, aged 17.4 +/- 3 years, with combined
      pituitary hormone deficiency (CPHD), caused by a PROP-1 gene defect.
      Adrenocorticotrophic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate
      (DHEAS) were determined prior to and following the administration of
      corticotropin-releasing hormone (CRH) in four of the five patients, while only
      basal values of ACTH, cortisol and DHEAS were determined in the fifth. In the
      four patients in whom a CRH test was carried out, the mean basal values of
      cortisol, ACTH and DHEAS were 289 +/- 140 nmol/l, 4.5 +/- 1.7 pmol/l and 0.26 +/-
      0.36 micromol/l, respectively. The corresponding post-CRH peak values were 584 +/
      204 nmol/l, 12.7 +/- 3.9 pmol/l and 0.43 +/- 0.41 micromol/l. In the fifth
      patient, basal ACTH, cortisol and DHEAS values were 4 pmol/l, 411 nmol/l, and
      2.33 micromol/l, respectively. Thus the basal and post CRH values of DHEAS (a
      marker of adrenarche) were low for age, while basal and post-CRH cortisol and
      ACTH values were within normal limits. For the interpretation of these findings
      two hypotheses can be proposed: 1) The PROP-1 gene is only expressed in the
      pituitary, and the role of PROP-1 is related to the maturation of the cells which
      synthesize the presumed adrenal androgen stimulating hormone (AASH). 2) The PROP
      1 gene is also expressed in the adrenal cortex and, when defective, the zona
      reticularis does not function appropriately. Regardless of the interpretation

PMID- 11592569
TI  - Maternal and fetal serum insulin-like growth factor-I (IGF-I) IGF binding protein
      3 (IGFBP-3), leptin levels and early postnatal growth in infants born
      asymmetrically small for gestational age.
AB  - This study was planned to investigate the relationship between birth weight and
      insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), and leptin
      levels in neonates with normal growth (appropriate for gestational age: AGA) and
      retarded growth (small for gestational age: SGA); and to evaluate these growth
      factors' effects in early postnatal growth. All newborns were full-term:
      gestational age 3,841 weeks. Of 50 neonates, 25 were SGA. IGF-I, IGFBP-3 and
      leptin levels were measured in maternal serum and venous cord blood at birth and
      at 15 days of life of neonates using specific RIAs. Maternal serum leptin
      concentrations were significantly higher than cord blood leptin concentrations (p
      < 0.001). Maternal serum IGF-I, IGFBP-3 and leptin levels did not show
      correlations with birth weight. In contrast, there were significantly positive
      correlations between birth weight and venous cord blood IGF-I, IGFBP-3 and leptin
      levels (p < 0.001). In the SGA group, the newborns with a slow postnatal growth
      pattern had lower umbilical cord serum IGF-I levels compared with newborns with a
      normal growth pattern. A similar result was also found in the AGA group. Similar
      results were not found for serum leptin and IGFBP-3. In conclusion, cord blood
      IGF-I, IGFBP-3 and leptin levels play an important role in the regulation of
      fetal and neonatal growth. It is likely that IGF-I has a more important role than
      the other factors in early postnatal growth.

PMID- 11592568
TI  - Syndrome of congenital adrenocortical unresponsiveness to ACTH. Report of six
      patients.
AB  - Familial glucocorticoid deficiency (FGD) or unresponsiveness to ACTH at the
      receptor level is a rare autosomal recessive hereditary syndrome characterized by
      a low cortisol level despite high serum ACTH concentration. Aldosterone levels
      are normal. The clinical entity generally presents in the first year of life with
      skin hyperpigmentation and hypoglycemic convulsions. Cortisol response to
      exogenous ACTH is also absent. Unresponsiveness to ACTH may be due to a mutation
      in the ACTH receptor; sometimes no mutation is found. We discuss the clinical and
      laboratory findings and genetic studies in six patients with a diagnosis of FGD.
      A homozygous V142L mutation was detected in three of the patients and a
      homozygous D103N mutation was detected in two patients.

PMID- 11592570
TI  - Relationships between levels of leptin and hematological parameters in healthy
      term infants.
AB  - In order to evaluate the role of leptin in neonatal hematological parameters, we
      studied the serum concentrations of leptin in relation to blood hemoglobin,
      leukocyte and platelet values in 30 healthy term infants. We also studied the
      serum concentrations of IGF-I and IGFBP-3 in relation to leptin concentrations.
      The mean concentrations of leptin, IGF-I and IGFBP-3 were 1.63 +/- 1.09, 24.65 +/
      10.04 and 976.05 +/- 214.50, respectively, at birth. A positive correlation was
      observed between leptin concentrations and birth weights of the infants. As no
      relationship could be found between concentrations of leptin and blood
      hemoglobin, leukocyte and platelet values, we could not determine any involvement
      of leptin in the regulation of physiologial hemoglobin, leukocyte and platelet
      concentrations at birth.

PMID- 11592571
TI  - Recombinant growth hormone treatment in short patients with thalassemia major:
      results after 24 and 36 months.
AB  - Treatment with recombinant growth hormone (rhGH), 0.6 IU/kg/week s.c., previously
      successfully conducted for one year, was continued in 15 (Group A) and 8 (Group
      B) short thalassemia major patients with reduced GH reserve, for two and three
      years, respectively. In Group A, height for chronological age (Ht SDSCA)
      increased significantly (p = 0.021) from the start of treatment, but the positive
      effect was only apparent because of the concomitant slight worsening of height
      for bone age (Ht SDSBA). Median deltaHt SDSCA/deltaHt SDSBA was <1.0 with respect
      to both the start (0.87) and the end of the first year of rhGH therapy (0.89).
      IGF-I levels increased significantly (p = 0.043) compared with values both at the
      start and at the end of the first year of rhGH therapy. In Group B neither Ht
      SDSCA nor Ht SDSBA differed statistically from starting values, the former having
      a positive trend and the latter a negative one. Median deltaHt SDSCA/deltaHt
      SDSBA was 0.92 with respect to the start, and 0.94 with respect to the end of the
      second year. IGF-I levels increased significantly (p = 0.043) with respect to
      starting values. Our data show that the encouraging results described from the
      first year of rhGH treatment did not persist during the second and third years,
      and we conclude that this is because increase in bone age with continued
      treatment is equal to, or slightly greater than the height age increase. We
      propose that patients with thalassemia major with short stature should receive
      rhGH treatment for only one year, and that more prolonged treatment should be
      reserved for selected adolescents who have psychological problems due to
      shortness; for these patients growth acceleration could represent the main goal,
      even if this leads to a substantially unchanged or slightly decreased final
      height.

PMID- 11592572
TI  - Assessment of the current status of iodine prophylaxis in Bosnia and Herzegovina
      Federation.
AB  - Assessment of the status of iodine prophylaxis was studied in 5,523
      schoolchildren randomly selected in all cantons in Bosnia and Herzegovina
      Federation (BHF). According to the iodine content of household salt samples, all
      cantons of BHF were divided into two groups: Group A: 95.5% of the salt used is
      produced in the Tuzla plant, in which the salt is iodized at 5-15 mg KI/kg salt,
      and 4.5% of the salt used is produced in the Pag plant, in which the salt is
      iodized at 20-30 mg KI/kg of salt, and Group B: 19.9% of the salt used is
      produced in the Tuzla plant and 80.1% in the Pag plant. In Group A the amount of
      iodine in salt was significantly lower than in Group B (11.4 mg/kg vs 18.9 mg/kg,
      P < 0.001). In Group A the prevalence of goiter was significantly higher than in
      Group B (32.6% vs 19.7%, P < 0.001). The highest prevalence of goiter was in
      Bosnian Podrinje Canton (51.2%) and Central Bosnian Canton (42.6%) while the
      lowest was in West Herzegovina Canton (12.9%). Significantly higher
      concentrations of urinary iodine were found in Group B than in Group A (82.6
      microg/l vs 75.2 microg/l, P < 0.001). In Group A the percentage of urine samples
      below 50 microg/l iodine was significantly higher than in Group B (35.6% vs
      26.9%, P < 0.001), but there was no difference in the percentage of urine samples
      with iodine values less than 100 microg/l (70.7 microg/l vs 68.25 microg/l, P >
      0.05). We conclude that FBH is an iodine deficient area and that the improvement
      of iodine prophylaxis is urgently required, primarily by increasing salt iodine
      content to 20-30 mg/kg, in order to eradicate endemic goiter.

PMID- 11592573
TI  - Profiles of obese children presenting for metabolic evaluation.
AB  - BACKGROUND: Obesity, increasingly prevalent among children, causes major
      morbidities, among which is earlier onset of type 2 diabetes mellitus (DM).
      METHODS: We reviewed charts of children aged 3 to 18 years (n=106). The
      population was divided into four age groups. Anthropomorphic measurements, family
      history, diet and exercise patterns, and selected endocrine/metabolic
      measurements were recorded, and descriptive statistics were calculated. RESULTS:
      Obesity in one or both parents correlated with a higher percent of ideal body
      weight (IBW) (p = 0.01). Fifty-eight percent of the children had first- or second
      degree relatives with a history of type 2 DM; 9% had relatives with type 1 DM.
      Fifty-four percent had dieted and exercised regularly. Mean onset of obesity was
      at 4.2 +/- 0.9 years. Mean cholesterol was elevated at 176 mg/dl. Average BMI was
      26.6 in the youngest children (Group 1; normal mean for this age approximately
      15.5), and increased to 37.8 in adolescents (Group 4; normal mean approximately
      21). Elevated TSH was present in <1% of the population. The number of patients
      with an abnormal insulin: glucose ratio (>1:4) increased with age. CONCLUSIONS:
      Childhood obesity in children is correlated with family histories of obesity and
      DM. Thyroid dysfunction is seldom found, although mild hypercholesterolemia and
      insulin insensitivity are prevalent, especially among adolescents.

PMID- 11592574
TI  - Effect of growth hormone treatment on hypoglycemia in a patient with both hepatic
      glycogen synthase and isolated growth hormone deficiencies.
AB  - A 7 year-old boy presenting with growth retardation, fasting hypoglycemia and
      ketoacidosis was diagnosed as having both idiopathic growth hormone (GH)
      deficiency and hepatic glycogen synthase (GS) deficiency caused by a homozygous
      mutation in exon 5 of the liver glycogen synthase gene (GYS-2). After four years
      of treatment with recombinant human GH, height increased from -4.9 SDS to -2.05
      SDS which is near his target height of -1.6 SDS. The GH treatment, however, did
      not prevent the fasting hypoglycemia. Blood glucose levels were only normalized
      after avoiding fasting intervals of more than five hours and the frequent feeding
      of protein-rich meals according to the guidelines for treatment of hepatic GS
      deficiency.

PMID- 11592575
TI  - Gliclazide-induced hepatitis, hemiplegia and dysphasia in a suicide attempt.
AB  - The drugs used to treat diabetes mellitus are diverse and include several
      classes. One class is sulfonylureas which primarily cause serum glucose reduction
      by stimulating the release of preformed insulin from the pancreatic islets.
      Gliclazide, a second generation sulfonylurea, is used to control glycemic levels
      in non-insulin-dependent diabetes mellitus. We report a 14 year-old non-diabetic
      girl who developed hepatitis, hemiplegia and dysphasia after ingestion of an
      overdose of gliclazide (20 mg/kg/day) in a suicide attempt. Our purpose is to
      draw attention to the severity of gliclazide-induced neurological signs. To the
      best of our knowledge, gliclazide-induced hemiplegia and dysphasia have not been
      previously reported in the literature.

PMID- 11592576
TI  - Neonatal goiter caused by expectorant usage.
AB  - A female newborn was admitted with the symptoms of mild respiratory distress,
      protruding tongue, hypotonicity, cutis marmorata, sclerema, myxedema, abdominal
      distension, and feeding problems on the first day of life. She had a huge neck
      mass, a large anterior and posterior fontanel, and hoarse cry. She had no
      umbilical hernia or jaundice. A history of maternal potassium iodine
      (expectorant) usage without doctor's advice was obtained; the mother had not
      attended a clinic throughout the pregnancy. On ultrasonographic examination, the
      thyroid right lobe was 53 x 31 mm and the left lobe was 34 x 31 mm. The results
      of thyroid hormone tests on the first day were as follows: T3 20 ng/dl (normal:
      32-216 ng/dl), T4 0.9 microg/dl (11.8-22.6 microg/dl), TSH 120 mIU/l (2.5-13.3
      mIU/l). This patient is presented to emphasize the role of hypothyroidism in drug
      induced neonatal goiter and to discuss the possibility of a life-threatening
      effect of congenital goiter, i.e. respiratory tract obstruction.

PMID- 11592577
TI  - Idiopathic hypothalamic dysfunction with precocious puberty and adipsic
      hypernatremia first presenting in adolescence.
AB  - BACKGROUND: Idiopathic hypothalamic dysfunction is a rare syndrome that has been
      described in young children. This syndrome is characterized by a disturbance of
      thirst regulation with hypernatremia, hyperosmolarity, and altered hypothalamic
      function. PATIENT REPORT: At age 6 years the reported patients presented with
      precocious puberty, by age 12 years she had hypernatremia presumed secondary to
      central diabetes insipidus and was treated with DDAVP, and at age 14 was
      identified to have hyperprolactinemia. At age 19 she presented with serum sodium
      of 185 mg/dl during an episode of illness associated with dehydration. After
      hydration, her sodium remained elevated. Arginine vasopressin was measurable but
      inappropriate to serum sodium, while urinary cyclic AMP response to vasopressin
      was appropriate. CONCLUSIONS: This is the first case of precocious puberty
      identified in association with the more classic features of idiopathic
      hypothalamic dysfunction, including later-onset hypernatremia, poor
      thermoregulatory function, obesity, and hyperprolactinemia.

PMID- 11592578
TI  - Neonatal hyperthyroidism in infants of mothers previously thyroidectomized due to
      Graves' disease.
AB  - Neonatal hyperthyroidism generally arises as a result of active maternal Graves'
      disease via transplacental passage of thyroid stimulating immunoglobulins (TSI).
      On occasions, production of these antibodies may continue after thyroid ablation,
      either surgically or with radioiodine therapy. We present data concerning three
      patients (two of them twins) whose mothers had previously undergone near-total
      thyroidectomy prior to conception. Two of the neonates had neonatal
      hyperthyroidism due to persistence of TSI in the mother, and the third due to
      relapse of the maternal Graves' disease during pregnancy. We recommend monitoring

PMID- 11592579
TI  - Primary hyperparathyroidism in an infant with three parathyroid glands and
      pulmonary calcinosis.
AB  - A 2 month-old male infant presented with severe hypercalcemia due to parathyroid
      hyperplasia. A total parathyroidectomy and partial heterotopic
      autotransplantation were carried out. Hypercalcemia recurred two months later.
      Normocalcemia was re-established after removing one half of the implanted tissue.
      Despite two separate surgical explorations and several imaging studies, including
      99mTc-sestamibi scintigraphy, ultrasonography, and MRI, only three parathyroid
      glands were found. Severe pulmonary calcinosis has not previously been reported
      in children with PHPT. In conclusion, developmental variations of the parathyroid
      glands may be difficult to identify with present imaging techniques. This may
      pose difficulties in management of PHPT. The present report describes pulmonary
      calcinosis as a sequela which can cause additional morbidity in these infants.

PMID- 11592580
TI  - Asymmetric crying facies and congenital hypothyroidism: report of two patients.
AB  - A congenital asymmetric crying facies (ACT) is caused by congenital hypoplasia or
      agenesis of the depressor anguli oris muscle. Associations of this facial defect
      with major congenital anomalies have been reported, most commonly in the
      cardiovascular system and less frequently involving the genitourinary,
      musculoskeletal, cervicofacial, respiratory, and rarely, the endocrine system. It
      is also well known that congenital hypothyroidism may be associated with other
      congenital malformations, especially with cardiac defects. Two newborn infants
      who had ACF associated with congenital heart defect and congenital hypothyroidism
      are described. To the best of our knowledge the association of ACF and congenital
      hypothyroidism has not previously been published.

PMID- 11592581
TI  - A variation of vitamin D deficiency in children.

PMID- 11592582
TI  - Diet of Belgian children with diabetes mellitus.

PMID- 11592583
TI  - Influence of tilapia mast cell lysate on vascular permeability.
AB  - Kinetics of vascular permeability was determined by measuring the amount of Evans
      blue leaked into the tilapia mast cell (tMC)-lysate injection site. Injection
      with tMC lysate enhanced the vascular permeability. The response consisted of
      three distinct phases, the first started immediately after the injection, the
      second started at about 2 h, reaching its maximum at 4 h, and the third response
      started at 12 h and continued for more than 24 h. Heating of the tMC lysate at
      100 degrees C for 10 min had no effect on the first response, while the second
      response was significantly reduced by heating at 50 degrees C for 10 min. The
      tMCs seem to have two kinds of factors that enhance vascular permeability. The
      tMC lysate induced Ca2+ uptake by cultured tilapia endothelial cells, indicating
      that tMC products directly activate the endothelial cells and increase vascular
      permeability similar to products of mammalian mast cells. These results indicate
      that with respect to influence on vascular permeability tilapia mast cells
      resemble the mast cells of mammals.

PMID- 11592584
TI  - Flow cytometric assessment of haemocyte sub-populations in the European flat
      oyster, Ostrea edulis, haemolymph.
AB  - The morphology and functions of haemocytes from the haemolymph of the European
      oyster, Ostrea edulis, were analysed by flow cytometry on the basis of cellular
      structures and incorporation of fluorescent markers. O. edulis circulating
      haemocytes appear to be composed of one to three cell populations based on cell
      size and granularity, with many individual variations. Analysis of haemocytes
      after propidium iodide staining indicated that the majority of oyster haemocytes
      are alive after sampling. The phagocytic activity level of haemocytes was
      analysed using fluorescent beads and this cell activity varied greatly depending
      on the oysters. The use of 3,3'dihexyloxacarbocyanine iodide (DIOC6) allowed the
      demonstration of several cell populations on the basis of labelled intensity. One
      to three cell sub-populations can be observed depending on the oysters. The
      haemocytes characterised by high granularity showed a strong fluorescence
      intensity related to high mitochondrial activity.

PMID- 11592585
TI  - Effect of macrophages and serum of fish susceptible or resistant to epizootic
      ulcerative syndrome (EUS) on the EUS pathogen, Aphanomyces invadans.
AB  - Epizootic ulcerative syndrome (EUS) is one of the most destructive diseases of
      fresh and brackish water farmed and wild fish in the Asia-Pacific region. The in
      vitro germination and growth of the propagules of the EUS pathogen, Aphanomyces
      invadans (= A. piscicida), were assessed in the presence of the head-kidney
      macrophages, serum, and serum heated to inactivate complement proteins, of three
      EUS-susceptible and one resistant fish species. The susceptible species were:
      striped snakehead (Channa striata), giant gourami (Osphronemus gouramy) and
      silver barb [Barbodes (= Puntius) gonionotus], and the resistant species was Nile
      tilapia (Oreochromis niloticus). Fish of all species were acclimatised to either
      low temperature (20 degrees C +/- 1.6) at which EUS is known to occur, or to high
      temperature (32 degrees C +/- 5.0) at which EUS does not occur, except for giant
      gouramis which were only studied at low temperature. The respiratory burst of the
      macrophages was assessed in the presence of A. invadans or the stimulant phorbol
      myristate acetate (PMA), and compared to that of controls. Anti-A. invadans
      antibody concentrations were assessed in all species except silver barbs. All
      assays were carried out at the same temperature, regardless of the temperature
      that the fish were kept at. Macrophages of all species other than snakeheads
      inhibited fungal germination at both temperatures, though only silver barb and
      gourami macrophages could inhibit germling growth. PMA increased the respiratory
      burst in nearly all cases. The respiratory burst in the presence of A. invadans
      was consistently lower than that of controls, though the difference was only
      significant in the case of snakeheads. The respiratory burst of all macrophage
      treatments was higher at a low temperature. Except in the case of PMA-stimulated
      macrophages, regressions between respiratory burst and inhibitory action were
      only found in susceptible species, suggesting that the respiratory burst is
      important in those species, but is unable to prevent the proliferation of A.
      invadans. Serum inhibited fungal germination in all cases other than low
      temperature tilapia, indicating that the EUS resistance of tilapia is not due to
      the serum. Inhibition of germling growth by serum only occurred in silver barbs
      and gourami. Heated serum did not inhibit germination in any case except that of
      high temperature snakehead, and in fact stimulated germination in the case of
      tilapia. Heating serum did not affect the growth inhibiting activity of silver
      barbs and gouramis, but it stimulated growth in some groups. At high temperatures
      snakeheads had high anti-A. invadans antibody concentrations, which may explain
      the inhibitory activity of their heated serum. A role for complement and
      antibodies in defence against A. invadans in susceptible species is suggested.

PMID- 11592586
TI  - Immunity to viral haemorrhagic septicaemia (VHS) following DNA vaccination of
      rainbow trout at an early life-stage.
AB  - Rainbow trout fry of average weight 0.5 g were vaccinated against viral
      haemorrhagic septicaemia (VHS) by intramuscular injection of 1 microg of plasmid
      DNA encoding the VHS virus glycoprotein gene. Challenge with a lethal dose of
      virus at two different time points, 9 and 71 days post-vaccination respectively,
      revealed that a highly protective and lasting immunity was established shortly
      after vaccination, in accordance with earlier experiments with larger fish. The
      defence mechanisms activated by the DNA vaccine are thus functional at an early
      life-stage in rainbow trout.

PMID- 11592587
TI  - Hypercapnic hypoxia compromises bactericidal activity of fish anterior kidney
      cells against opportunistic environmental pathogens.
AB  - Acute hypoxia can cause massive fish and shellfish mortality. Less clear is the
      role that chronic sublethal hypoxia might play in aquatic animal health. This
      study tested whether production of reactive oxygen species (ROS) and bactericidal
      activity of fish phagocytic cells are suppressed under the conditions of
      decreased oxygen and pH and increased carbon dioxide which occur in the blood and
      tissue of animals exposed to sublethal hypoxia. Anterior head kidney (AHK) cells
      of the mummichog, Fundulus heteroclitus, were exposed in parallel to normoxic
      (pO2=45 torr, pCO2=3.8 torr, pH=7.6) or hypoxic (pO2=15 torr, pCO2=8.0 torr,
      pH=7.0) conditions and stimulated with a yeast cell wall extract, zymosan. or
      live Vibrio parahaemolyticus. Hypercapnic hypoxia suppressed zymosan-stimulated
      ROS production by 76.0% as measured in the chemiluminescence assay and by 58.5%
      in the nitroblue tetrazolium (NBT) assay. The low O2, high CO2 and low pH
      conditions also suppressed superoxide production by 75.0 and 47.3% as measured by
      the NBT assay at two different challenge ratios of cells:bacteria (1:1 and 1:10,
      respectively). In addition to its effects on ROS production, hypercapnic hypoxia
      also reduced bactericidal activity by 23.6 and 72.5% at the 1:1 and 1:10
      challenge ratios, respectively. Low oxygen levels alone (pO2=15 torr, pCO2=0.76
      torr, pH=7.6) did not significantly compromise the killing activity of cells
      challenged with equal numbers of V. parahaemolyticus. At the higher 1:10
      AHK:bacteria challenge ratio, low oxygen caused a small (26.3%) but significant
      suppression of bactericidal activity as compared to aerial conditions (pO2=155
      torr, pCO2=0.76 torr, pH=7.6). This study demonstrates that while hypoxia alone
      has detrimental effects on immune function, suppression of phagocytic cell
      activity is compounded by naturally occurring conditions of hypercapnia and low
      pH, creating conditions that might be exploited by opportunistic pathogens. These
      results indicate that the adverse health effects of chronic hypercapnic hypoxia
      might greatly exceed the effects of low oxygen alone.

PMID- 11592588
TI  - Lysozyme activity and protein concentration in the haemolymph of the flat oyster
      Ostrea edulis (L.).
AB  - Lysozyme activity and protein concentration in the haemolymph of the flat oyster
      Ostrea edulis were investigated. These biochemical constituents of the haemolymph
      could be an indication of the physiological condition and vitality of the defence
      system of an animal. Haemolymph protein and lysozyme in oysters were examined
      over an 18 month period to determine their relationship with the strain of
      oyster, the season, the site, and parasitism by Bonamia ostreae. Haemolymph
      protein concentration exhibited seasonal fluctuations and varied between strains.
      Levels of protein in oysters highly infected with B. ostreae were slightly
      depressed but not significantly so. Haemolymph lysozyme varied greatly between
      individuals but no correlation was found between lysozyme levels and infection of
      oysters by B. ostreae.

PMID- 11592589
TI  - A transglutaminase involved in the coagulation system of the freshwater crayfish,
      Pacifastacus leniusculus. Tissue localisation and cDNA cloning.
AB  - The crayfish haemolymph can form stable and insoluble clots by a transglutaminase
      (TGase)-catalysed crosslinking reaction between the soluble clotting protein
      molecules from the plasma. The crayfish haemocytes, both semigranular and
      granular cells, as well as the muscle tissue, contain TGase activity, whereas the
      hepatopancreas and plasma have no TGase activity. A 3199 bp cDNA encoding a TGase
      was isolated from a crayfish haemocyte cDNA library. The deduced protein
      comprises 766 amino acid residues and has a calculated molecular mass of between
      85,930 and 86,034 kDa due to four amino acid variations. This gene is expressed
      as a single 4.9 kb transcript exclusively in the haemocytes and at very low
      levels in muscle and the hepatopancreas. Sequence comparison shows that this
      TGase has significant similarities to other TGases from invertebrates and
      mammals.

PMID- 11592590
TI  - Effect of Tetramicra brevifilum (Microspora) infection on respiratory-burst
      responses of turbot (Scophthalmus maximus L.) phagocytes.
AB  - In vitro assays were performed to investigate microsporidian-induced
      intracellular and extracellular production of reactive oxygen species (ROS) by
      peritoneal-exudate adherent (PEA) cells from turbot. ROS production was
      quantified using the fluorescent reagents OxyBURST Green H2HFF BSA
      (extracellular) and OxyBURST Green H2DCFDA succinimidyl ester (intracellular).
      Five days before assay, the cells had been elicited in vivo by intraperitoneal
      injection of sodium thioglycollate or spores of Tetramicra brevifilum.
      Elicitation with spores led to a marked increase in the proportion of neutrophils
      among PEA cells. PEA cells from normal turbot showed considerable extracellular
      and intracellular ROS production in response to microsporidian spores. By
      contrast, PEA cells from microsporidian-infected turbot showed considerably
      reduced extracellular and intracellular ROS production in response to
      microsporidian spores. Extracellular ROS production was affected by the addition
      of infected turbot serum to the assay medium, regardless of whether the PEA cells
      had been obtained from normal or infected fish. The presence of microsporidian
      infected turbot serum significantly reduced intracellular ROS production by PEA
      cells elicited with microsporidian spores. These results suggest that (a)
      microsporidian spores partially suppress the repiratory-burst response of turbot
      phagocytes; and (b) infected turbot serum contains substances capable of
      modulating the respiratory-burst response of turbot phagocytes to microsporidian
      spores.

PMID- 11592591
TI  - Bone disease in primary biliary cirrhosis: independent indicators and rate of
      progression.
AB  - BACKGROUND/AIMS: To identify indicators of osteoporosis and to determine the rate
      of bone loss in patients with primary biliary cirrhosis (PBC). METHODS: Bone
      mineral density of the lumbar spine and hip was measured at annual intervals over
      7 years of follow-up in 176 patients with PBC. RESULTS: Osteoporosis (t-score
      below -2.5) was found in 20% of patients and occurred 32.1 times more frequently
      in patients with PBC than expected. Patients with histologic stage 3 or 4 disease
      had a 5.4-fold increased risk of osteoporosis compared to patients with stage 1
      or 2. Age, body mass index, advanced stage (3 or 4), and history of fractures
      were the only independent indicators of osteoporosis. After 3 years of follow up,
      the rate of bone loss in patients with stage 1 or 2 increased and equaled that
      seen in patients with stage 3 or 4. Serum bilirubin level was the only variable
      independently associated with the rate of bone loss over time. CONCLUSIONS:
      Severity of the liver disease contributes significantly to the severity of bone
      disease in PBC. PBC patients who are older, thinner and have more advanced liver
      disease may have the most benefit from bone density measurements and treatment
      for their osteoporosis.

PMID- 11592592
TI  - Apolipoprotein E polymorphism, a marker of disease severity in primary biliary
      cirrhosis?
AB  - BACKGROUND/AIMS: To determine whether the apolipoprotein E (apo-E) polymorphism
      is associated with the risk of primary biliary cirrhosis (PBC), the severity of
      the disease and its response to ursodeoxycholic acid (UDCA) therapy. METHODS: The
      apo-E genotype was determined in 72 PBC patients. Genotype and allele
      distributions were compared with those found in the French general population.
      Laboratory parameters obtained before and after 1- and 4-year UDCA treatment were
      compared according to the apo-E allele carrier status. RESULTS: Apo-E allele and
      genotype distributions were similar between PBC patients and the general
      population. At the time of diagnosis, the epsilon4 allele carriers were younger
      (P < 0.05), had higher bilirubin (P < 0.05) and IgG (P < 0.001) levels and a
      lower prothrombin index (P < 0.01) than epsilon2 (homozygous + heterozygous) or
      epsilon3 homozygous allele carriers. After 4-year UDCA therapy, the decrease in
      serum alkaline phosphatase and in alanine and aspartate aminotransferase
      activities was lower in percentage in the epsilon4 than in other epsilon allele
      carriers (P < 0.01). CONCLUSIONS: Although apo-E polymorphism does not appear to
      confer susceptibility to PBC, it probably influences PBC progression and response
      to UDCA. The epsilon4 allele may identify patients with high risk of severe
      disease and poor response to treatment.

PMID- 11592593
TI  - Early shifts of adrenal steroid synthesis before and after relief of short-term
      cholestasis.
AB  - BACKGROUND/AIMS: Chronic inflammatory diseases are characterised by a relative
      reduction of cortisol and adrenal androgens. The time point of appearance of
      these alterations is not known. Cholestasis may be a model of short-term
      inflammation to study early alterations of steroidogenesis. METHODS: We
      investigated 18 patients with cholestasis before and after therapeutic abolition
      of cholestasis (compared to nine control subjects, Co). RESULTS: Serum tumour
      necrosis factor (TNF) was increased in cholestatic patients as compared to Co (P
      at least <0.01). Co as compared to cholestatic patients without tumours had
      elevated levels of plasma adrenocorticotropic hormone (ACTH) and serum
      dehydroepiandrosterone sulfate (DHEAS) but serum cortisol levels were similar.
      Levels of ACTH and DHEAS in relation to serum IL-6 or TNF were higher in Co as
      compared to the cholestatic subgroup without tumours, whereas serum cortisol in
      relation to these cytokines was similar. In both subgroups of cholestatic
      patients, we observed the typical inflammation-dependent shift of adrenal
      hormones into the direction of cortisol in relation to DHEAS. Cholestatic
      patients with malignant tumours demonstrated an intermediate response pattern.
      CONCLUSIONS: Short-term cholestasis for 5-12 days induced marked alterations of
      adrenal steroidogenesis which partly resemble the changes observed in chronic
      inflammatory diseases.

PMID- 11592594
TI  - The prognostic value of histology in the assessment of patients with Budd-Chiari
      syndrome.
AB  - BACKGROUND/AIMS: It is unclear whether treatment of patients with Budd-Chiari
      syndrome (BCS) should be based on liver histology, as large histopathological
      studies have not been performed. We investigated the relationship between the
      histopathological findings and survival. METHODS: We studied the clinical
      features and findings on biopsy specimens in 45 patients with BCS who were
      admitted to four tertiary referral medical centers. Histological findings, i.e.
      congestion, necrosis, inflammation and fibrosis, were graded. Survival was
      assessed in relation to histological findings and clinical features at the time
      of diagnosis as well as in relation to subsequent treatment with or without
      portosystemic shunting. RESULTS: Centrilobular congestion, centrilobular
      necrosis, lobular inflammation and portal inflammation were not significantly
      related to survival. In addition, there was no association between either
      pericentral or periportal fibrosis and survival. Univariate analysis revealed
      that the prothrombin time and Child-Pugh score were significantly related to
      survival (P = 0.005 and Ptrend = 0.02, respectively). Multivariate analysis
      yielded the Child-Pugh score, serum alanine aminotransferase (ALT) and treatment
      with portosystemic shunting as independent prognostic indicators. CONCLUSIONS: We
      found no evidence for a relationship between early liver pathology and survival.
      Child-Pugh score, serum ALT and portosystemic shunting appeared to be prognostic
      indicators for patients with BCS.

PMID- 11592595
TI  - Venesection therapy of insulin resistance-associated hepatic iron overload.
AB  - BACKGROUND/AIMS: The association of hepatic iron overload with metabolic
      disorders has been coined as the insulin resistance-associated hepatic iron
      overload syndrome (IR-HIO). METHODS: Fifty-six IR-HIO patients were phlebotomized
      either weekly (n = 14) or bimonthly (n = 42) and compared with C282Y homozygotes
      and with ten IR-HIO patients treated by a low calorie diet alone. RESULTS: In
      venesected patients, the median amount of mobilized iron was 0.6 g in 2.8 months
      in females and 1.8 g in 5 months in males. Mobilized iron did not differ
      depending on the frequency of venesections or HFE genotype. When compared with
      C282Y homozygotes, IR-HIO patients had a similar amount of mobilized iron, but
      three-fold serum ferritin levels. The presenting symptoms (chronic fatigue and/or
      polyarthralgias) improved in 6/7 patients. Phlebotomies were well tolerated. In
      patients treated by a low calorie diet, serum ferritin levels remained stable.
      CONCLUSIONS: In IR-HIO patients, body iron stores are significantly increased,
      overestimated by serum ferritin, not modified by a low calorie diet, and safely
      removed by phlebotomies. Based on these data and on studies indicating that iron
      excess is associated with increased risk for hepatic fibrosis, cancer and
      cardiovascular disorders, venesection therapy can be recommended in IR-HIO
      patients.

PMID- 11592596
TI  - Role of small-conductance Ca2+-dependent K+ channels in in vitro nitric oxide
      mediated aortic hyporeactivity to alpha-adrenergic vasoconstriction in rats with
      cirrhosis.
AB  - BACKGROUND/AIMS: In vitro studies have shown that cirrhotic aortas are
      hyporeactive to the contractile effect of vasoconstrictors because upregulated
      endothelial nitric oxide-synthase (NOS) overproduces nitric oxide (NO). Although
      stimulation of endothelial small-conductance Ca2+-dependent K+ (SK(Ca)) channels
      may elicit vasorelaxation in normal arteries, the role of these channels in
      cirrhosis-induced hyporeactivity is unknown. Thus, the aim of the present study
      was to investigate the role of endothelial SK(Ca) channels in cirrhosis-induced,
      NO-mediated, in vitro aortic hyporeactivity to alpha1-adrenergic
      vasoconstrictors. METHODS: Isolated thoracic aortas from cirrhotic and normal
      rats were used. The effects of apamin, a selective SK(Ca) channel blocker, were
      measured on the vascular reactivity to phenylephrine. In addition, SK(Ca) channel
      protein expression was studied. The effects of iberiotoxin and charybdotoxin,
      blockers of other K(Ca) channels, were also studied in cirrhotic aortas. RESULTS:
      Apamin suppressed cirrhosis-induced aortic hyporeactivity to phenylephrine in an
      endothelium-dependent, NOS-inhibitor-sensitive manner. SK(Ca) channel protein was
      overexpressed in cirrhotic aortic walls. Iberiotoxin abolished cirrhosis-induced
      aortic hyporeactivity to phenylephrine in an endothelium-dependent but NOS
      inhibitor-resistant manner. Charybdotoxin did not induce any significant increase
      in phenylephrine-elicited contraction. CONCLUSIONS: In cirrhotic aortas, the
      overexpression and overactivity of endothelial SK(Ca) channels contributes to in
      vitro NO-mediated hyporeactivity to the contractile action of alpha1-adrenergic
      agonists.

PMID- 11592597
TI  - Identification of osmosensitive and ammonia-regulated genes in rat astrocytes by
      Northern blotting and differential display reverse transcriptase-polymerase chain
      reaction.
AB  - BACKGROUND/AIMS: The hepatic encephalopathy (HE) is in part the result of
      astrocyte swelling with alterations of glial function. Detoxification of ammonia
      may be one mechanism by which astrocyte swelling is triggered in HE. METHODS: The
      differential display polymerase chain reaction (DDRT-PCR) and Northern blot
      analysis were used for study the functional consequence of cell volume changes
      and ammonia on gene expression in primary rat astrocytes. RESULTS: Differentially
      expressed cDNA products were identified with about 92% homology to genes coding
      for mouse proline rich protein expressed in brain (PRTB), rat clusterin, elongin,
      and human Kelch motif containing protein. As shown by Northern blot analysis,
      PRTB and clusterin mRNA levels were upregulated by 19-64% after 4-8 h by both
      ammonia and hypoosmolarity. Elongin mRNA expression increased by 97% in response
      to ammonia but slightly by hypoosmolarity. Further, hypoosmotic exposure for 1-24
      hours but not ammonia led to an increase of 80% in KMCP mRNA levels. CONCLUSIONS:
      The identification of these genes offers the opportunity to identify unrecognized
      molecular mechanisms of HE. The finding that several genes are induced by both,
      hypoosmolarity and ammonia, supports the view that astrocyte swelling is a major,
      but not the only pathogenetic event in HE.

PMID- 11592598
TI  - Transglutaminase-mediated cross-linking is involved in the stabilization of
      extracellular matrix in human liver fibrosis.
AB  - BACKGROUND/AIMS: Lysyl oxidase-mediated cross-linking contributes to the
      stabilization of collagen in liver fibrosis. We have investigated
      transglutaminase-mediated cross-linking, to determine if it participates in the
      stabilization of extracellular matrix in human liver fibrosis. METHODS:
      Transglutaminase activity was assessed in vitro by incorporation of biotinylated
      amine into liver proteins. The product of the transglutaminase-catalyzed cross
      linking reaction, Nepsilon(gamma-glutamyl)lysine, and the extracellular proteins
      cross-linked by it, were localized by immunohistochemistry in fibrotic livers.
      The cross-linked complexes were extracted from liver tissue, immunopurified and
      characterized by Western blot. RESULTS: Transglutaminase, detected by
      immunohistochemistry, Western blot and by enzymatic activity, was found in higher
      amounts in fibrotic than in normal liver. The Nepsilon(gamma-glutamyl)lysine
      cross-link, undetectable in normal liver, was present extracellularly in fibrotic
      liver, where it was co-distributed with osteonectin, mostly in inflammatory areas
      submitted to an intense remodeling. Cross-linking of osteonectin by
      transglutaminase was confirmed by Western blot. In parasitic fibrosis
      transglutaminase also originates from the parasite. CONCLUSIONS: Transglutaminase
      mediated cross-linking occurs in liver extracellular matrix during the early,
      inflammatory, stage of liver fibrosis, whereas cross-linking by pyridinoline
      occurs mostly later in the fibrotic process. This could lead to the development
      of new anti-fibrotic treatments targeted to a specific stage of fibrosis.

PMID- 11592599
TI  - Effect of angiotensin II type 1 receptor blockade on experimental hepatic
      fibrogenesis.
AB  - BACKGROUND/AIMS: The aim of this study was to investigate whether in the liver,
      as in other tissues, there is evidence that angiotensin II, acting via the
      angiotensin II type 1 receptor (AT1-R), plays a role in fibrogenesis. METHODS:
      Sprague-Dawley rats were divided into three groups; sham, bile duct ligated (BDL)
      and BDL + AT1-R antagonist, irbesartan. Real time RT-PCR was utilised to assess
      gene expression of the AT1 receptor, TGF-beta1 and alpha1 (I) collagen in the
      liver. TGF-beta1 and alpha1 (I) collagen mRNA expression and localisation were
      also assessed by in situ hybridisation. TGF-beta1 activity was assessed by using
      the TGF-beta inducible gene product betaig-h3. Fibrosis was assessed by the
      Knodell scoring system, tissue hydroxyproline content and picro-sirius red
      staining. RESULTS: Real time RT-PCR revealed that there was a 6-fold up
      regulation in AT1 receptor expression in BDL animals compared with shams. This
      was associated with marked increases in TGF-beta1, betaig-h3 and alpha1 (I)
      collagen gene expression which were attenuated by AT1-RA treatment. However, AT1
      RA therapy produced no significant change in liver histology or hydroxyproline
      content. CONCLUSIONS: These results suggest that in the liver angiotensin II may
      play an important role in the fibrogenic response to injury. However, whether
      treatment with an AT1-RA will be of therapeutic benefit remains to be determined.

PMID- 11592600
TI  - Modulation of collagen XVIII/endostatin expression in lobular and biliary rat
      liver fibrogenesis.
AB  - BACKGROUND/AIMS: The liver is the major source of collagen XVIII (C18), the
      precursor of the angiogenesis inhibitor endostatin. In human liver C18 is mainly
      expressed by hepatocytes. However, its quantitative and temporospatial expression
      patterns during liver fibrogenesis are unknown. METHODS: We used RNA
      quantification and in situ hybridization combined with cell-specific markers to
      study C18 compared to procollagen alpha1(I) and tissue inhibitor of
      metalloproteinases-1 (TIMP-1) mRNA expression in acute (single dose of CCl4) and
      chronic (biliary) rat liver fibrogenesis. RESULTS: C18 transcripts were only
      found in hepatocytes and bile duct epithelia of normal and fibrotic livers, and
      occasionally in arterial myocytes and hepatic stellate cells. 72 h after CCl4
      injection, C18 mRNA levels remained unchanged, while procollagen alpha1(I) mRNA
      was increased at 72 h and TIMP-1 mRNA peaked at 12 h (P < 0.05). In biliary
      fibrosis C18 mRNA levels increased 1.8-fold, contrasting with 20- and 4-fold
      elevated procollagen alpha1(I) and TIMP-1 transcript levels, respectively.
      CONCLUSIONS: Hepatocytes and bile duct epithelia are the predominant sources of
      C18 in normal and fibrotic rat liver. Contrary to procollagen alpha1(I) and TIMP
      1, C18 expression remains constant in acute fibrogenesis and is upregulated in
      biliary fibrosis. Modulation of epithelial C18 expression and its processing to
      endostatin could allow a liver-specific anticancer therapy.

PMID- 11592601
TI  - Antifibrotic effect of silymarin in rat secondary biliary fibrosis is mediated by
      downregulation of procollagen alpha1(I) and TIMP-1.
AB  - BACKGROUND/AIMS: Silymarin reduces hepatic collagen accumulation by 35% in rats
      with secondary biliary cirrhosis. The aim of the present study was to explore its
      antifibrotic mechanism. METHODS: Thirty female adult Wistar rats were allocated
      to (1) bile duct occlusion, (2) bile duct occlusion and oral silymarin at 50
      mg/kg per day, and (3) sham operation and oral silymarin at 50 mg/kg per day.
      Steady-state mRNA levels for procollagen alpha1(I), tissue inhibitor of
      metalloproteinases-1 (TIMP-1), and transforming growth factor (TGF) beta1 were
      determined by multi-probe ribonuclease protection assay. RESULTS: After 6 weeks
      of bile duct occlusion, liver collagen content was increased 12-fold, when
      compared with the sham-operated controls. These animals displayed 17-, 6.5- and
      16-fold higher transcript levels for procollagen alpha1(I), TIMP-1 and TGFbeta1
      (P < 0.01). Silymarin downregulated elevated procollagen alpha1(I), TIMP-1 and
      TGFbeta1 mRNA levels by 40-60% (P < 0.01). These lowered hepatic profibrogenic
      transcript levels correlated with decreased serum levels of the aminoterminal
      propeptide of procollagen type III. CONCLUSIONS: Silymarin suppresses expression
      of profibrogenic procollagen alpha1(I) and TIMP-1 most likely via downregulation
      of TGFbeta1 mRNA in rats with biliary fibrosis. The serum procollagen type III
      propeptide level mirrors profibrogenic mRNA expression in the liver.

PMID- 11592602
TI  - Quantitation of hepatic hepatitis C virus RNA in patients with chronic hepatitis
      C. Relationship with severity of disease, viral genotype and response to
      treatment.
AB  - BACKGROUND/AIMS: To determine the correlation between hepatic hepatitis C virus
      (HCV) RNA and histological lesions, viral genotype or response to alpha
      interferon therapy. METHODS: Forty-three patients with chronic hepatitis C (14
      sustained responders (SR) and 29 non-sustained responders (NSR)) were studied. A
      liver tissue sample was obtained before and 1 year after treatment. Quantitation
      of hepatic HCV-RNA was performed by competitive PCR. RESULTS: Before treatment,
      HCV-RNA was detectable in all liver samples. There was no association between
      hepatic HCV-RNA and the severity of liver lesions. There was a significant
      association between old age and hepatic HCV-RNA (P = 0.03). There was an
      association, at the limit of significance, between genotype 1 and high hepatic
      HCV-RNA amounts (15 x 106 and 4.1 x 10(6) copies/g, P = 0.05). Pre-treatment
      hepatic HCV-RNA amounts were lower in SRs than in others (0.65 x 10(6) and 13.2 x
      10(6) copies/g, P = 0.0002). After treatment, no liver HCV-RNA was detectable in
      the SRs while in the NSRs, the HCV-RNA amounts were unchanged. CONCLUSIONS: The
      amount of hepatic HCV-RNA is correlated to genotype and response to interferon
      therapy but not to histologic lesions. Hepatic HCV-RNA clearance is observed in
      SRs, suggesting viral eradication.

PMID- 11592603
TI  - Long-term efficacy of interferon alpha-2b and lamivudine in combination compared
      to lamivudine monotherapy in patients with chronic hepatitis B. An Italian
      multicenter, randomized trial.
AB  - BACKGROUND/AIMS: To evaluate the therapeutic efficacy of interferon alpha-2b and
      lamivudine in combination compared to lamivudine monotherapy in patients with
      chronic hepatitis B. METHODS: One hundred and fifty-one patients were randomly
      assigned to receive either recombinant interferon alpha-2b (nine million units
      three times per week) and lamivudine (100 mg/daily per os) for 24 weeks or
      lamivudine alone (100 mg/daily per os) for 52 weeks. Patients were followed up
      for a further 48 weeks. RESULTS: Sustained HBeAg seroconversion with undetectable
      serum levels of HBV DNA was observed in 25 of 76 patients (33%) treated with the
      combination therapy and in 11 of 75 patients (15%) treated with monotherapy
      (P=0.014). Histological improvement defined as a reduction of at least two points
      in the inflammation score as compared with pretreatment score was observed in 35
      of 76 patients (46%) treated with combination therapy and in 20 of 75 patients
      (27%) treated with monotherapy (P=0.021). Both therapeutic regimens were well
      tolerated. CONCLUSIONS: Six-month treatment with interferon alpha-2b and
      lamivudine in combination appeared to increase the rate of sustained HBeAg
      seroconversion compared to 1-year lamivudine monotherapy. However, the potential
      benefit of combining lamivudine and interferon should be investigated further in
      studies with different regimens of combination therapy.

PMID- 11592604
TI  - The natural history of primary biliary cirrhosis: of genes and cooperation.

PMID- 11592605
TI  - Cytokines and neuroendocrine dysregulation in obstructive cholestasis:
      pathophysiological implications.

PMID- 11592606
TI  - Lamivudine-interferon combination therapy for chronic hepatitis B: further
      support but no conclusive evidence.

PMID- 11592607
TI  - Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona
      2000 EASL conference. European Association for the Study of the Liver.

PMID- 11592608
TI  - Abnormal hepatic enhancement on CT in congestive heart failure.

PMID- 11592609
TI  - Steatosis in chronic hepatitis C: can weight reduction improve therapeutic
      efficacy?

PMID- 11592610
TI  - Bronchoconstrictive properties of inhaled 8-epi-PGF2alpha in healthy and heaves
      susceptible horses.
AB  - The 8-epi-PGF2alpha is a marker of oxidative stress which is increased in lungs
      of asthmatic humans and heaves-susceptible horses. 8-Epi-PGF2alpha has also been
      demonstrated to be an in vitro and in vivo bronchoconstrictor in humans and
      rodents. We hypothesised that inhaled 8-epi-PGF2alpha was a bronchoconstrictor in
      healthy and heaves-susceptible horses in clinical remission. The effect on
      ventilatory mechanics of nebulised 8-epi-PGF2alpha was compared to that of
      PGF2alpha and U46619, a thromboxane A2 agonist. Pulmonary resistance (R(L)) and
      dynamic compliance (Cdyn) were assessed in six healthy horses and in six heaves
      susceptible horses in clinical remission before (baseline) and immediately after
      a single inhalation challenge of 1 mg 8-epi-PGF2alpha PGF2alpha, or U46619 and
      placebo. R(L) and Cdyn were unchanged after inhalation of 8-epi-PGF2alpha in
      healthy horses. In heaves-susceptible horses, 8-epi-PGF2alpha induced a
      significant increase of R(L) and a significant decrease of Cdyn when compared to
      baseline values. Differences between R(L) and Cdyn values after 8-epi-PGF2alpha
      inhalation and those of placebo inhalation were not significant. Differences with
      healthy horses were not significant. PGF2alpha and U46619 induced a significant
      bronchoconstriction in healthy (R(L) and Cdyn versus baseline) and heaves
      susceptible horses (R(L) and Cdyn, versus baseline and placebo), the R(L)
      increase in heaves-susceptible horses after PGF2alpha inhalation was
      significantly higher than that in healthy horses. Our results suggest that 8-epi
      PGF2alpha is not a bronchoconstrictor in healthy horses, and a bronchoconstrictor
      far less efficient than PGF2alpha and U46619 at the same dose in heaves
      susceptible horses.

PMID- 11592611
TI  - Herd factors associated with the seroprevalences of Actinobacillus
      pleuropneumoniae serovars 2, 3 and 9 in slaughter pigs from farrow-to-finish pig
      herds.
AB  - This cross-sectional epidemiologic study was conducted in 150 randomly selected
      farrow-to-finish pig herds to investigate descriptive epidemiological
      characteristics of infections with three different serovars of Actinobacillus
      pleuropneumoniae, and to identify risk factors for the within-herd
      seroprevalences of these serovars. Different farm characteristics (n = 28) were
      examined as potential risk factors for the percentage of pigs with antibodies
      against serovars 2, 3 and 9. The presence of antibodies was measured using an
      indirect ELISA. Logistic regression analyses were used to assess the associations
      between the potential risk factors and the proportion of seropositive pigs. The
      median within-herd seroprevalences were 95% (range: 0-100%), 100% (range: 10
      100%), and 35% (range: 0-100%) for serovars 2, 3, and 9, respectively. There was
      a positive association (P < 0.001) between each of these serovars. The within
      herd seroprevalence of serovar 2 was significantly higher in farms that purchased
      gilts from > or = 2 origin herds (OR = 2.33; P < 0.05) and in farms with poor
      biosecurity measures (OR = 4.62; P < 0.05). The proportion of pigs seropositive
      for serovar 3 was significantly higher when tested pigs were slaughtered in May
      August and in November-December (OR = 5.96; P < 0.001), in herds without a
      growing unit (OR = 2.63; P < 0.01), and in herds with a direct air-entry into the
      finishing unit (OR = 1.92; P < 0.05). The within-herd seroprevalence of serovar 9
      increased significantly in herds with poor biosecurity measures (OR = 1.76; P <
      0.05). The study documented that infections with A. pleuropneumoniae serovars 2,
      3, and 9 were very common in the selected herds, and that the sero
      epidemiological characteristics and risk factors showed some variation depending
      on the serovar. The purchase policy of gilts and biosecurity measures are risk
      factors that can be improved fairly easily on pig farms.

PMID- 11592612
TI  - The negative effects of the residues of ivermectin in cattle dung using a
      sustained-release bolus on Aphodius constans (Duft.) (Coleoptera: Aphodiidae).
AB  - This paper reports the findings of two trials into the effects of the treatment
      of cattle with ivermectin slow-release (SR) bolus on the larval development of
      the dung beetle Aphodius constans Duft. Rectal faecal samples were collected
      prior to treatment and every 3 and 2 weeks in a first and second trial,
      respectively, and up to 156 days post-administration of the SR bolus. Faecal
      ivermectin concentration reached a peak at 63 days post-treatment (1427 ng g(-1))
      and ivermectin was detected up to 147 days post-treatment in the first trial (7.2
      ng g(-1)). First stage larvae of A. constans were reared with control or
      contaminated dung and adult beetles were counted after emergence. In the first
      trial, the comparison of pairwise samples showed that ivermectin prevented the
      development of larval A. constans until day 105, while at day 135 the rate of
      emergence was still significantly lower than the corresponding series of control
      (p < 0.05). In the second trial, the difference between control and treated
      series remained significant until 143 days post-treatment, with no emergence
      until 128 days post-administration of SR bolus to cattle. These results show the
      negative effect of ivermectin on the development of larval A. constans, even at a
      low concentration (38.4 ng g(-1)). The administration of ivermectin sustained
      release bolus to cattle was highly effective in killing dung beetle larvae for
      approximately 143 days after treatment. The results were similar when dung was
      obtained from a single animal kept alone, or from a blending of faecal pats
      obtained from a group of animals kept in field conditions during the whole trial
      period.

PMID- 11592613
TI  - Immortalized goat milk epithelial cell lines replicate CAEV at high level.
AB  - Primary milk epithelial cells were isolated from CAEV-uninfected goats and three
      cell lines designated TIGMEC-1, TIGMEC-2 and TIGMEC-3 were established. The three
      cell lines retained their morphological characteristics of epithelial cells and
      expressed specific epithelial cytokeratin marker as well as the immortalizing
      SV40 large T antigen. The kinetics of growth of TIGMEC1, TIGMEC2 and TIGMEC3 cell
      lines showed a doubling time of 24-48 hours while the parental cell lines became
      senescent after the passage 6 in cell culture. Like the parental primary cells,
      the three cell lines were found to be highly sensitive to CAEV-pBSCA, an
      infectious molecular clone of CAEV-CO strain, and to a French isolate CAEV-3112.
      TIGMEC cell lines infected with CAEV-pBSCA became chronically infected producing
      high virus titers in absence of cytopathic effects. These cell lines may be
      useful for study of the possible physiological alterations in mammary epithelial
      cells infected with small ruminant lentiviruses and their consequences on milk
      quality. On an other hand, these cell lines can be used to study their role in
      virus transmission and pathogenesis.

PMID- 11592614
TI  - Monitoring porcine reproductive and respiratory syndrome virus infection status
      in swine herds based on analysis of antibodies in meat juice samples.
AB  - An indirect ELISA test was developed as a novel tool aimed at monitoring the herd
      infection status of swine herds. Meat juice samples from pig carcasses were
      analysed for the presence of antibodies against porcine reproductive and
      respiratory syndrome virus (PRRSV). A study of samples from herds with known PRRS
      status was undertaken. The PRRS status of the herds was evaluated based on the
      analysis of blood samples by another serological test (blocking ELISA) capable of
      differentiating between infection with PRRSV of the American type and European
      type. The specificity of the indirect ELISA test on meat juice samples was 0.98.
      The sensitivity of the test depended on the type of the PRRSV strain involved.
      The apparent prevalence in herds infected with the American type of PRRSV was
      0.44. The apparent prevalence in herds infected with the European type of PRRSV
      was 0.64. Herd level sampling and herd level criteria for assessing the PRRS
      status of herds by the new test were developed. Herds were classified as PRRS
      negative or PRRS seropositive based on 10 meat juice samples collected randomly
      at slaughter throughout a 3-month-period. Herd PRRS status classification by the
      indirect ELISA was validated in 47 herds by collection of blood samples from the
      herds. Eighteen herds were classified as PRRS negative by both test systems.
      Twenty-nine herds were classified as PRRS seropositive by both test systems.
      Acceptable herd classification was achieved using this test.

PMID- 11592615
TI  - Determination of selamectin in dog plasma by high performance liquid
      chromatography with automated solid phase extraction and fluorescence detection.
AB  - A method is described for the determination of selamectin in dog plasma, using
      High-Performance Liquid Chromatography (HPLC) with fluorescence detection
      (excitation and emission wavelengths fixed at 355 and 465 nm, respectively). The
      fluorescent derivative was obtained by condensation reaction with trifluoroacetic
      anhydride and N-methylimidazole. The method employs 1 mL plasma samples and gives
      linear calibration graphs (r = 0.999) over the concentration range studied (0.5
      50 ng mL(-1)). Automatic solid phase extraction using the benchmate procedure was
      used for sample preparation. This method permits the determination of selamectin
      at levels as low as 0.1 ng mL(-1) and its suitability was demonstrated by a
      pharmacokinetic study on a dog receiving the therapeutic dose (Spot-on
      administration).

PMID- 11592616
TI  - Pathological and immunohistochemical study of the abomasum and abomasal lymph
      nodes in goats experimentally infected with Haemonchus contortus.
AB  - Histopathological changes and the distributions of T and B lymphocytes and IgG
      producing plasma cells were recorded in the abomasum and abomasal lymph nodes of
      goats 3, 7 and 21 weeks post-infection (wpi) after an experimental infection with
      H. contortus. The low rate of worm recovery by 3 wpi (5.6%) might have been due
      to larvae death as suggested by the presence of granulomas in the abomasal mucosa
      at 3 and 7 wpi, or simply due to a poor larval establishment. Marked increase in
      the secretion of mucus by mucous cells together with an abundant infiltration of
      eosinophils, mast cells, CD3+ T lymphocytes, CD79a+ B cells, IgG+ plasma cells
      and globule leukocytes were recorded in the abomasal mucosa, especially at 7 wpi.
      Except for the globule leukocytes, this reaction decreased substantially by week
      21, suggesting this cell type may have been involved in rejection of adult
      nematodes. The abomasal lymph nodes showed marked hyperplasia, particularly of
      CD79a+ B cells and IgG+ plasma cells in all infected goats. These reactions may
      have been responsible for the reduction in the number of worms found in the
      abomasum between 3 and 7 wpi.

PMID- 11592617
TI  - Agglutination-separation reactions of red blood cells sensitized with Newcastle
      disease virus: quantities, agglutination characteristics, and serology of altered
      virus and HN spikes released following neuraminidase reactivation.
AB  - Red blood cells (RBC) become sensitized following the elution of strain 575
      Newcastle disease virus (NDV). The neuraminidase (NA) in the haemagglutinin (HA)
      sialic acid configuration is inactive. The HA on sensitized RBC agglutinates
      normal RBC. The sialic acid on normal RBC initiated reactivation of the NA-a
      newly described function. Then normal-sensitized RBC agglomerates separated at 37
      degrees C in the irreversible agglutination-separation (AS) reactions. With
      separation the AS products. HN spikes (150-200 kDa) and altered NDV, which
      contain fewer HN spikes than intact allantoic NDV, were removed from the
      sensitized RBC and the NDV membrane. Extraction of HN spikes from the membrane
      required more sialic acid than the removal of AS products from RBC. Thus 2
      reactions were delineated for the orderly removal. Amounts of each released AS
      product suggest the source of the HN spikes. AS reactions and ether treatment of
      NDV increased the HA titres up to 19.2 fold. HA-sialic acid configurations were
      estimated by the amounts of normal RBC agglutinated by sensitized RBC and also by
      agglutination with fetuin. Elution of B1 vaccine, HN spikes from ether-treated
      NDV as well as AS products separated on sephadex resulted in incompletely
      sensitized RBC; fewer configurations were titrated with normal RBC; all failed to
      respond to anti-NA antibody. In contrast, sensitized RBC or suspensions of 575
      NDV, but not the B1 vaccine strain, responded to both anti-NA and anti-HA
      antibody. Sensitization, slow elution, and responding to anti-NA antibody, which
      was accompanied by fluorescent foci on sensitized RBC, required intact NDV and
      the infrequent HA-sialic acid configuration. The NA was inactive for the HA
      sialic acid configuration but cleaved fetuin, indicating substrate specificity.
      An inactive NA would allow time for fusion and NDV penetration rather than
      elution by an active NA early in NDV infection.

PMID- 11592618
TI  - Influence of HMB (beta-hydroxy-beta-methylbutyrate) on antibody secreting cells
      (ASC) after in vitro and in vivo immunization with the anti-Yersinia ruckeri
      vaccine of rainbow trout (Oncorhynchus mykiss).
AB  - In practice, protection of fish against disease by immunization is of limited
      effectiveness. Therefore, research is concentrated on how to improve the potency
      and efficacy of vaccines and how to optimally activate the cell-mediated immunity
      and the specific antibody response. In the present study, the influence of HMB
      (beta-Hydroxy-beta-methylbutyrate) on the antibody secreting cells (ASC) after
      both in vitro and in vivo immunization of rainbow trout (Oncorhynchus mykiss)
      with the anti-yersiniosis vaccine was studied. For in vitro immunization, the
      spleens from 160 fish were sampled and placed each in 35 mm sterile wells with
      medium containing HMB at concentrations of 0, 0.1, 1, 5, 10, 25, 50 or 100
      microg/mL of medium. The spleens from 80 fish were injected with the vaccine and
      incubated at 14 degrees C for 10 days. For the in vivo study, fish were fed
      pellets containing HMB at doses of 0, 10, 25 and 50 mg/kg bw per day. After 2
      weeks of HMB supplementation, the fish were immunized by intraperitoneal
      injection of the vaccine. At 7, 14, 18, 21, 28 and 35 days after immunization,
      pronephros were taken from 10 fish in each group for testing. When analyzed by
      the ELISPOT assay, HMB increased the number of splenic ASC after in vitro
      immunization at concentrations between 10 and 100 microg/mL (P < 0.05). Dietary
      HMB also increased the number of total and specific ASC when the fish were
      vaccinated in vivo. In conclusion, the results of the present study showed that
      HMB increases the levels of specific ASC after both in vitro and in vivo
      immunization of rainbow trout with the anti-Yersinia ruckeri vaccine.

PMID- 11592619
TI  - Myocastor coypus as a reservoir host of Fasciola hepatica in France.
AB  - To clarify the role of the nutria Myocastor coypus in the epidemiology of
      domestic fasciolosis in Loire-Atlantique (department of western France), 438
      nutrias were trapped in 9 humid areas of the department and 304 nutrias were
      trapped in 3 farms where Fasciola hepatica was present; all animals were
      necropsied. Liver flukes were found in 160 nutrias: 38 nutrias randomly taken in
      the department (8.7%) and 122 trapped in fasciolosis areas (40.1%). The average
      parasitic burden was 5.7 flukes per nutria. Sixty-five percent of the liver
      flukes measured more than 18 mm (size of sexual maturity). The coproscopic
      examinations carried out on 144 infected nutrias showed that 90% of the infected
      nutrias shed fluke eggs. The hatching rate was 39.6%. Two groups of 100 Lymnaea
      truncatula snails, originating from 2 different populations, were exposed to F.
      hepatica miracidiae hatched from eggs collected from infected nutrias. The
      prevalence of the infection was 74% and 58.6% in the 2 groups of snails. The
      average redial burden was 6.2 rediae per snail. The total number of metacercariae
      was 72.4 metacercariae per snail producing cercariae. Two groups of 5 sheep were
      orally infected by 150 metacercariae of nutria or sheep origin, respectively. The
      installation rates of F. hepatica in sheep were respectively 31.6% and 29.6% for
      the two groups. Specific antibody kinetics of sheep were similar whether the
      metacercariae were of nutria or sheep origin. M. coypus allows the complete
      development of F. hepatica and releases parasitic elements that are infective for
      domestic ruminants. Because of its eco-ethologic characteristics, the nutria
      could be a potential wild reservoir of F. hepatica in France.

PMID- 11592620
TI  - Toxicokinetics of ergovaline in the horse after an intravenous administration.
AB  - The toxicokinetics of ergovaline (an ergopeptine mycotoxin present in some
      grasses infected with endophytic fungus of the genus Neotyphodium) were studied
      after intravenous administration of a single dose of 15 microg/kg bwt in four
      gelding horses. Plasma ergovaline concentrations were measured by high
      performance liquid chromatography, and the kinetic data were described by a three
      compartment model. The elimination half-life and the total clearance of
      ergovaline were found to be 56.83 +/- 13.48 min and 0.020 +/- 0.004 L/min x kg,
      respectively. According to the toxicological data previously reported in the
      horse, and in spite of the very low dose administered, clinical signs were
      observed, including excessive coolness of the ears and the nose, excessive
      sweating and prostration.

PMID- 11592621
TI  - Formation of a direction map by projection learning using Kohonen's self
      organization map.
AB  - In this paper, we propose a modification of Kohonen's self-organization map (SOM)
      algorithm. When the input signal space is not convex, some reference vectors of
      SOM can protrude from it. The input signal space must be convex to keep all the
      reference vectors fixed on it for any updates. Thus, we introduce a projection
      learning method that fixes the reference vectors onto the input signal space.
      This version of SOM can be applied to a non-convex input signal space. We applied
      SOM with projection learning to a direction map observed in the primary visual
      cortex of area 17 of ferrets, and area 18 of cats. Neurons in those areas
      responded selectively to the orientation of edges or line segments, and their
      directions of motion. Some iso-orientation domains were subdivided into selective
      regions for the opposite direction of motion. The abstract input signal space of
      the direction map described in the manner proposed by Obermayer and Blasdel
      [(1993) J Neurosci 13: 4114-4129] is not convex. We successfully used SOM with
      projection learning to reproduce a direction-orientation joint map.

PMID- 11592622
TI  - Balanced neurons: analysis of leaky integrate-and-fire neurons with reversal
      potentials.
AB  - A new technique is presented for analyzing leaky integrate-and-fire neurons that
      incorporates reversal potentials, which impose a biologically realistic lower
      bound to the membrane potential. The time distribution of the synaptic inputs is
      modeled as a Poisson process. The analysis is carried out in the Gaussian
      approximation, which comparison with numerical simulations confirms is most
      accurate in the limit of a large number of inputs. The hypothesis that the
      observed variability in the spike times of cortical neurons is caused by a
      balance of excitatory and inhibitory synaptic inputs is supported by the results
      for the coefficient of variation of the interspike intervals. Its value decreases
      with both increasing numbers and amplitude of inputs, and is consistently lower
      than 1.0 over a wide range of realistic parameter values. The dependence of the
      output spike rate upon the rate, number, and amplitude of the synaptic inputs, as
      well as upon the value of the inhibitory reversal potential, is given.

PMID- 11592623
TI  - Epileptiform activity in a neocortical network: a mathematical model.
AB  - A simple mathematical model describing the generation and propagation of
      epileptiform activity in a cerebral cortical network is presented. The model
      consists of a system of nonlinear delay differential equations. Physiological
      properties are taken into account as nonlinear transmission of signals at the
      synapse, temporal and spatial summation of incoming signals at the soma, active
      membrane characteristics, and dendritic and axonal propagation times. The
      influence of the connectivity and the temporal parameters on the oscillatory
      properties of the model is studied. The computer simulations are in agreement
      with experimental observations in cortical networks: whereas a weak excitatory or
      strong inhibitory synaptic connection strength produces a stationary status with
      short-lasting responses to external stimuli, increases in excitation or decreases
      in inhibition induce spontaneous and stimulus-evoked rhythmic discharges.
      Synaptic burst-like activity is observed only for an intermediate range of
      excitatory and inhibitory connection strengths and external inputs. The form and
      duration of the bursts can also be controlled by the temporal parameters. The
      results demonstrate that relatively simple mathematical equations are sufficient
      to model some of the network properties underlying the generation and propagation
      of epileptiform activity.

PMID- 11592624
TI  - Noise-induced transition in excitable neuron models.
AB  - We studied the influence of noisy stimulation on the Hodgkin-Huxley neuron model.
      Rather than examining the noise-related variability of the discharge times of the
      model--as has been done previously--our study focused on the effect of noise on
      the stationary distributions of the membrane potential and gating variables of
      the model. We observed that a gradual increase in the noise intensity did not
      result in a gradual change of the distributions. Instead, we could identify a
      critical intermediate noise range in which the shapes of the distributions
      underwent a drastic qualitative change. Namely, they moved from narrow unimodal
      Gaussian-like shapes associated with low noise intensities to ones that spread
      widely at large noise intensities. In particular, for the membrane potential and
      the sodium activation variable, the distributions changed from unimodal to
      bimodal. Thus, our investigation revealed a noise-induced transition in the
      Hodgkin-Huxley model. In order to further characterize this phenomenon, we
      considered a reduced one-dimensional model of an excitable system, namely the
      active rotator. For this model, our analysis indicated that the noise-induced
      transition is associated with a deterministic bifurcation of approximate
      equations governing the dynamics of the mean and variance of the state variable.
      Finally, we shed light on the possible functional importance of this noise
      induced transition in neuronal coding by determining its effect on the spike
      timing precision in models of neuronal ensembles.

PMID- 11592625
TI  - The effect of subthreshold prepulses on the recruitment order in a nerve trunk
      analyzed in a simple and a realistic volume conductor model.
AB  - The influence of subthreshold depolarizing prepulses on the threshold current-to
      distance and the threshold current-to-diameter relationship of myelinated nerve
      fibers has been investigated. A nerve fiber model was used in combination with
      both a simple, homogeneous volume conductor model with a point source and a
      realistic, inhomogeneous volume conductor model of a monofascicular nerve trunk
      surrounded by a cuff electrode. The models predict that a subthreshold
      depolarizing prepulse will desensitize Ranvier nodes of fibers in the vicinity of
      the cathode and thus cause an increase in the threshold current of a subsequent
      pulse to activate these fibers. If the increase in threshold current of the
      excited node is large enough, the excitation will be accompanied by a strong
      hyperpolarization of adjacent nodes, preventing the propagation of action
      potentials in these fibers. As fibers close to the electrode are more
      desensitized by prepulses than more distant ones, it is possible to stimulate
      distant fibers without stimulating such fibers close to the electrode. Moreover,
      as larger fibers are more desensitized than smaller ones, smaller fibers have
      lower threshold currents than larger fibers up to a certain distance from the
      electrode. The realistic model has provided an additional condition for the
      application of this method to invert nerve fiber recruitment, i.e., real or
      virtual anodes should be close to the cathode. When using a cuff electrode for
      this purpose, in the case of monopolar stimulation the cuff length (determining
      the position of the virtual anodes) should not exceed twice the internodal length
      of the fibers to be blocked. Similarly, the distance between cathode and anodes
      should not exceed the internodal length of these fibers when stimulation is to be
      applied tripolarly.

PMID- 11592626
TI  - Frequency response functions and information capacities of paired spider
      mechanoreceptor neurons.
AB  - Pseudorandom white-noise stimulation followed by direct spectral estimation was
      used to obtain linear frequency response and coherence functions from paired, but
      dynamically different, spider mechanosensory neurons. The dynamic properties of
      the two neuron types were similar with either mechanical or electrical
      stimulation, showing that action potential encoding dominates the dynamics. Phase
      lag data indicated that action potential initiation occurs more rapidly during
      mechanical stimulation, probably in the distal sensory dendrites. Total
      information capacity, calculated from coherence, as well as information per
      action potential, were both similar in the two types of neurons, and similar to
      the few available estimates from other spiking neurons. However, information
      capacity and information per action potential both depended strongly on neuronal
      firing rate, which has not been reported before.

PMID- 11592627
TI  - Sensitivity of basic oscillatory mechanisms for pattern generation and detection.
AB  - Intrinsic oscillators are the basic building blocks of central pattern
      generators, which model the neural circuits underlying pattern generation.
      Coupled intrinsic oscillators have been shown to synchronize their oscillatory
      frequencies and to maintain a characteristic pattern of phase relationships.
      Recently, oscillatory neurons have also been identified in sensory systems that
      are involved in decoding phase information. It has been hypothesized that the
      neural oscillators are part of neural circuits that implement phase-locked loops
      (PLLs), which are well-known electrical circuits for temporal decoding. Thus,
      there is evidence that intrinsic neural oscillators participate in both temporal
      pattern generation and temporal pattern decoding. The present paper investigates
      the dynamics underlying forced oscillators and forced PLLs, using a single
      framework, and compares both their stability and sensitivity characteristics. In
      particular, a method for assessing whether an oscillatory neuron is forced
      directly or indirectly, as part of a PLL, is developed and applied to published
      data.

PMID- 11592628
TI  - Generalized dimension of the intersection between EEGs.
AB  - The generalized dimension defined by [Mandelbrot (1995) J Fourier Anal Appl
      special J.P. Kahane issue: 409-432] was applied to studying the interrelationship
      between various parts of human cerebral cortex in different functional
      conditions. Taking EEG signals from different brain areas as different sets, the
      generalized dimensions of their intersections were calculated to describe the
      interrelationship between them. The results showed that the generalized
      dimensions of intersections in different brain states decreased according to the
      following order: rest with eyes open, closed, light sleep, and deep sleep. The
      generalized dimensions of intersections related to the left or right temporal
      lobe were higher than the others when the subjects was doing mental arithmetic,
      and there was a decrease when the subjects listened to soft classical music. In
      addition, it was found that there was a noticeable difference in singular spectra
      between epileptic patients and normal subjects, irrespective of whether the
      epileptic patient was experiencing a seizure or not.

PMID- 11592629
TI  - Mixed state on a sparsely encoded associative memory model.
AB  - We analyzed symmetric mixed states corresponding to the so-called concept
      formation on a sparsely encoded associative memory model with 0-1 neurons. Three
      types of mixed states--OR, AND, and a majority decision--are described as typical
      examples. Each element of the OR mixed state is composed of corresponding memory
      pattern elements by means of the OR operation. The other two types are similarly
      defined. By analyzing their equilibrium properties through self-consistent signal
      to-noise analysis and computer simulation, we found that the storage capacity of
      the OR mixed state diverges in a sparse limit, but that the other states do not
      diverge. In addition, we found that the optimal threshold values, which maximize
      the storage capacity for the memory pattern and the OR mixed state, coincide with
      each other in the spare limit. We conclude that the OR mixed state is a
      reasonable representative of mixed state in the sparse limit.

PMID- 11592630
TI  - Stenotrophomonas maltophilia interaction with human epithelial respiratory cells
      in vitro.
AB  - Bacteria of Stenotrophomonas maltophilia have been isolated with increasing
      frequency from the airways of cystic fibrosis (CF) patients, usually following P.
      aeruginosa infections, but their adherence to human epithelial respiratory cells
      has never been investigated. In this study, various S. maltophilia strains were
      seen to adhere to epithelial respiratory cells in vitro, mainly along
      intercellular junctions. Bacteria could also enter into host cells, as determined
      by the gentamicin exclusion assay and transmission electron microscopy. Cells co
      incubated with P. aeruginosa and S. maltophilia exhibited a significantly
      decreased adherence of these latter bacteria. No decrease in S. maltophilia
      adherence was observed when co-infection was carried out with heat-killed P.
      aeruginosa or when respiratory cells were first incubated with P. aeruginosa,
      before incubation with S. maltophilia. Our data suggest that P. aeruginosa
      infections do not account for the increased prevalence of S. maltophilia in CF
      patient airways, that thermolabile products from P. aeruginosa can control the
      adherence of S. maltophilia to respiratory cells and also that these two bacteria
      do not compete for cell receptors.

PMID- 11592631
TI  - Chemotaxis of oral treponemes toward sera and albumin of rabbit.
AB  - The motility and chemotaxis of human oral spirochetes Treponema denticola ATCC
      35404, T. medium ATCC 700293, and T. vincentii ATCC 35580 were examined by a
      capillary assay method. Of five sera three human oral treponemes were dominantly
      chemoattractant to the rabbit serum. The checkerboard analysis of chemotaxis
      toward rabbit serum clearly showed that the motile T. denticola cells swam toward
      the culture media containing higher concentrations of the rabbit serum. T.
      denticola chemotaxis to the rabbit serum was clearly reduced by heating serum,
      and rabbit albumin contributed by 60 to 70% to its chemotaxis to the rabbit
      serum. Western blotting analysis demonstrated that these treponemes possessed
      rabbit albumin-binding polypeptides with approximate molecular sizes of 65 kDa
      and 70 kDa. Immunoelectron microscopy demonstrated that a 65 kDa rabbit albumin
      binding polypeptide was located on the outer envelopes, suggesting that the
      rabbit albumin-binding polypeptide is responsible for chemotaxis toward rabbit
      serum.

PMID- 11592632
TI  - Iron-Mediated regulation of alkaline proteinase production in Pseudomonas
      aeruginosa.
AB  - We analyzed the regulation by iron of alkaline proteinase (AP) production in
      Pseudomonas aeruginosa. Extracellular AP production was detected from the mid
      logarithmic to the stationary phase by an antibody-based assay system, and was
      strongly repressed by iron in the medium. This repression was shown by Northern
      hybridization and primer extension to occur at the level of transcription. The
      primer extension analysis revealed that the start point of transcription of AP
      gene was the nucleotide position -84 from the start point of translation.
      Furthermore, we investigated whether this transcriptional repression involved
      PvdS protein. Using the mutant strain of pvdS, the alternative sigma factor gene
      revealed that the PvdS protein is required for the full expression of AP, and a
      previous study showed that expression of pvdS is also repressed by iron.
      Therefore, we thought that one mechanism of repression of AP production operated
      through reduction of the PvdS protein level. Purified AP decomposed the
      transferrin, and released iron from it. Purified AP added to the medium
      containing transferrin as the only iron source enhanced the growth of P.
      aeruginosa. Moreover, mutation in the AP gene decreased the growth rate in the
      medium containing the transferrin as the only iron source. These results clearly
      indicated that AP expression should occur in a free-iron-deficient environment
      and emphasized the importance of AP to iron acquisition in the infection site.

PMID- 11592633
TI  - CD3- bone marrow cells augment the generation of cytotoxic T lymphocytes showing
      a preference for the X-chromosome linked gene product of stimulator cells.
AB  - Responder cells, composed of both a limited number of nylon wool-passed lymph
      node (NW-LN) cells and an excess number of CD3+ cell-depleted bone marrow (CD3-
      BM) cells from the same strain of mice, were stimulated with allogeneic spleen
      cells in vitro. The CD3- BM cells augmented the generation of allogeneic major
      histocompatibility complex (MHC) class I specific cytotoxic T lymphocytes (CTL)
      from NW-LN cells. C3H/He (H-2k, C3H background) responder cells were stimulated
      with either B10.D2 (H-2d, B10 background) or BALB/c (H-2d, BALB background)
      spleen cells. In the former stimulation, the CTL induced lysed B10.D2 target
      cells more efficiently than the BALB/c cells. Furthermore, these CTL lysed more
      (B10.D2 x BALB/c) F1 male target cells than (BALB/c x B10.D2) F1 male. In the
      latter stimulation, the CTL lysed more BALB/c than B10.D2 cells, and more
      (BALB/c) x B10.D2) F1 male than (B10.D2 x BALB/c) F1 male. The reciprocal mixed
      lymphocyte cultures (MLC) were carried out, in which BALB/c responder cells were
      stimulated with either C3H/He or B10.BR (H-2k, B10 background) spleen cells. In
      the former stimulation, the CTL induced lysed more C3H/He or (C3H/He x B10.BR) F1
      male target cells than B10.BR or (B10.BR x C3H/He) F1 male, and in the latter,
      the reciprocal results were obtained. These results suggested that the CTL
      induced had a preference for the X-chromosome linked gene products (Xlgp),
      besides the specificity for the allogeneic MHC class I, of the mice used as
      stimulator.

PMID- 11592634
TI  - Plasminogen activator production in a rat model of Pneumocystis carinii
      pneumonia.
AB  - Several studies have indicated that the serine protease urokinase-plasminogen
      activator (uPA) is an important factor in host defense against pulmonary
      pathogens. To gain a better insight into the role of uPA in Pneumocystis carinii
      (P. carinii) pneumonia (PCP), we evaluated PA production in alveolar macrophages
      (AMs) obtained from rats with steroid-induced PCP. Treatment with cortisone
      acetate favored PCP in 91% of rats. In the bronchoalveolar lavage (BAL) samples
      of immunosuppressed rats both with and without PCP, we observed a decrease in uPA
      activity as well as a decrease in cell number. Urokinase-PA production by AMs was
      reduced in rats treated with cortisone alone. However, an increase in cell
      associated uPA was observed in rats with PCP. This increase appears to be
      produced in response to P carinii infection. In fact, when AMs obtained from
      untreated healthy or immunosuppressed uninfected rats were challenged with P
      carinii, a significant increase in PA activity in cell lysates was observed,
      though a lower response was obtained in cortisone-treated animals. Our results
      suggest that healthy AMs respond to the presence of P carinii with an increase in
      uPA production and that this response in immunodepressed rat-AMs is partially
      impaired.

PMID- 11592635
TI  - Detection of virulence associated genes in clinical strains of vibrio mimicus.
AB  - A total of 42 clinical strains of Vibrio mimicus were examined for the presence
      of virulence associated genes toxR, toxS, toxT, tcpP, ctx and tcpA by PCR assay.
      Almost all strains were shown to have the toxR gene, while the toxS gene was
      found in 27 strains. On the other hand, five strains possessed both toxT and tcpP
      genes, but others had neither. Only two strains were positive for amplification
      of the ctx gene, whereas no PCR product with tcpA primers was detected. The
      results indicate the incomplete copies of virulence cascade in V mimicus strains.
      The pathogenesis and epidemic potential of this species is also discussed.

PMID- 11592636
TI  - Characteristics of macrolide-resistant Mycoplasma pneumoniae strains isolated
      from patients and induced with erythromycin in vitro.
AB  - Some patients with Mycoplasma pneumoniae infection are clinically resistant to
      antibiotics such as erythromycin, clarithromycin, or clindamycin. We isolated M.
      pneumoniae from such patients and found that one of three isolates showed a point
      mutation in the 23S rRNA gene. Furthermore, 141 EM-sensitive clinical isolates of
      M. pneumoniae were cultured in broth medium containing 100 microg/ml of
      erythromycin (EM). Among 11 EM-resistant strains that grew in the medium, point
      mutations in the 23S rRNA were found in 3 strains at A2063G, 5 strains at A2064G
      and 3 strains at A2064C. The relationship between the point mutation pattern of
      these EM-resistant strains and their resistance phenotypes to several macrolide
      antibiotics was investigated.

PMID- 11592639
TI  - Amplified detection of DNA and analysis of single-base mismatches by the
      catalyzed deposition of gold on Au-nanoparticles.
AB  - A novel amplification route for DNA detection based on the deposition of gold on
      a 10 nm Au-colloid/avidin conjugate label acting as a 'seeding' catalyst, is
      described. Microgravimetric quartz-crystal-microbalance measurements are employed
      to transduce the catalyzed deposition of gold on the piezoelectric crystals.
      Three different DNA detection schemes are described: (i) analysis of a 27-base
      nucleic acid fragment; (ii) analysis of the entire M13phi DNA (7229 bases); and
      (iii) detection of a single-base mismatch in a DNA. Ultrasensitive detection of
      DNA is accomplished by the catalyzed deposition of gold, detection limit
      approximately 1 x 10(-15) M.

PMID- 11592642
TI  - Separation and determination of protocatechuic aldehyde and protocatechuic acid
      in Salivia miltorrhrza by capillary electrophoresis with amperometric detection.
AB  - Capillary electrophoresis with amperometric detection was applied to separate and
      determine protocatechuic aldehyde and protocatechuic acid in Salivia miltorrhrza
      preparations. The electrode used was a 0.3 mm diameter carbon disk electrode
      fixed in a wall-jet with amperometric detection. Under the optimum conditions,
      the two analytes were separated completely within 8 min. Excellent linearity was
      obtained in the concentration ranges of 0.25-100.0 microg ml(-1) and 0.50-100.0
      microg ml(-1) for protocatechuic aldehyde and protocatechuic acid, respectively.
      The detection limits were 0.10 microg ml(-1) of protocatechuic aldehyde and 0.25
      microg ml(-1) of protocatechuic acid, which were found to be lower than those of
      other methods that determine protocatechuic aldehyde (3,4-dihydroxybenzaldehyde)
      and protocatechuic acid (3,4-dihydrobenzoic acid) simultaneously. The mean
      recoveries of protocatechuic aldehyde and protocatechuic acid were 97.4% and
      103.3%. This method has been successfully applied to monitor these two components
      in real samples such as Salivia miltorrhrza and its two traditional Chinese
      medicinal preparations.

PMID- 11592643
TI  - Determination of the active ingredients in Gastrodia rhizoma by capillary
      electrophoresis with electrochemical detection.
AB  - A simple, reliable and reproducible method, based on capillary electrophoresis
      (CE) with electrochemical detection (ED), for the determination of five active
      ingredients and three carbohydrates in extracts of Gastrodia rhizoma is described
      in this work. The main active ingredients are gastrodin, 4-hydroxybenzyl alcohol,
      vanillyl alcohol, 4-hydroxybenzylaldehyde and vanillin. Operated in a wall-jet
      configuration, a 300 microm diameter carbon disc electrode was used as a working
      electrode, with a good response at +1000 mV (vs. SCE) for 4-hydroxybenzyl
      alcohol, vanillyl alcohol, 4-hydroxybenzylaldehyde and vanillin; a 300 microm
      diameter copper disc electrode exhibits a good response at +650 mV (vs. SCE) for
      gastrodin, sucrose, glucose and fructose. Under optimum conditions, 4
      hydroxybenzyl alcohol, vanillyl alcohol, 4-hydroxybenzylaldehyde and vanillin in
      100 mmol l(-1) borate buffer (pH 9.2) and gastrodin, sucrose, glucose and
      fructose in 50 mmol l(-1) sodium hydroxide buffer were baseline separated within
      18 min. The response was linear over two orders of magnitude with a detection
      limit (S/N = 3) in the range 3 x 10(-7)-1.8 x 10(-6) mol l(-1) for all eight
      analytes. This method was successfully used in the analysis of traditional
      Chinese medicine, and the assay results were satisfactory.

PMID- 11592644
TI  - Multiresidue analysis of pesticides in vegetables and fruits using two-layered
      column with graphitized carbon and water absorbent polymer.
AB  - A high-throughput multiresidue analysis of pesticides in non-fatty vegetables and
      fruits was developed. The method consisted of a single extraction and a single
      clean-up procedure. Food samples were extracted with ethyl acetate and the
      mixture of extract and food dregs were poured directly into the clean-up column.
      The clean-up column consisted of two layers of water-absorbent polymer (upper)
      and graphitized carbon (lower), which were packed in a reservoir (75 ml ) of a
      cartridge column. The polymer removed water in the extract while the carbon
      performed clean-up. In a recovery test, 110 pesticides were spiked and average
      recoveries were more than 95% from spinach and orange. Most pesticides were
      recovered in the range 70-115% with RSD usually < 10% for five experiments. The
      residue analyses were performed by the extraction of 12 pesticides from 13
      samples. The two methods resulted in similar residue levels except chlorothalonil
      in celery, for which the result was lower with the proposed method. The results
      confirmed that the proposed method could be applied to monitoring of pesticide
      residue in foods.

PMID- 11592645
TI  - Phenolics in selected European hardwood species by liquid chromatography
      electrospray ionisation mass spectrometry.
AB  - The phenols in beech (Fagus sylvatica), birch (Betula pendula) and ash (Fraxinus
      excelsior) wood dusts were compared using a mass spectrometer fitted with an
      electrospray ionisation interface with liquid chromatographic separation.
      Hardwood dust is a carcinogen, and an analysis of the polyphenol profile is a
      useful method for identifying the dust source in workplace air. The mass
      spectrometer was operated in both the negative and positive ion modes. Phenolic
      compounds were identified by comparing mass spectra and retention times from
      liquid chromatography with those for standard compounds and data in the
      literature. The phenol contents of the studied wood species varied considerably,
      and only a few common compounds were found in them.

PMID- 11592647
TI  - Detection of aflatoxins (G(1-2), B(1-2)), sterigmatocystin, citrinine and
      ochratoxin A in samples contaminated by microbes.
AB  - A method is described for the simultaneous determination of common aflatoxins
      (G1, G2, B1, B2) and their precursor sterigmatocystin, and also citrinine and
      ochratoxin A. The method was applied to a building material matrix artificially
      contaminated with mycotoxin-producing fungi. The method includes extraction,
      sample pre-treatment and reversed-phase HPLC separation with tandem mass
      spectrometric identification and quantification using electrospray ionisation on
      a quadrupole ion trap mass analyser (ESI-MS-MS). Aqueous methanol was used in the
      initial extraction and solvent partitioning and solid phase extraction in the
      purification of samples. The HPLC separation was run on-line with the ESI-MS-MS
      detection. The limit of quantification of the procedure was 200 ng for all
      compounds. Recoveries of the sample pre-treatment varied from 28 to 99%. The
      average compound- and concentration-dependent accuracy and precision (RSD) were
      21 and 113%, respectively. The method includes small sample volumes
      (approximately 1 g in 20 ml) and few, non-labour intensive, sample treatment
      steps. It should allow for a high throughput of samples with good prospects of
      automation.

PMID- 11592648
TI  - Dot-blot amperometric genosensor for detecting a novel determinant of beta
      lactamase resistance in Staphylococcus aureus.
AB  - A new electrochemical hybridisation genosensor for the detection of resistant
      bacteria has been developed. This device relies on the immobilisation of a 50-mer
      oligonucleotide target, unique to a novel determinant of beta-lactamase
      resistance in Staphylococcus aureus, onto an electrochemical transducer. This
      genosensor is based on a concept adapted from classical dot-blot DNA analysis,
      but implemented in an electrochemical biosensor configuration. Amperometric
      transduction and an enzyme label method, that increases the genosensor
      sensitivity, are the main features of this new approach. In addition to the
      adapted dot-blot format, a double hybridisation assay, in which two different
      labelled probes were used, is reported. This procedure, if combined with
      polymerase chain reaction (PCR), allows determination of the genotype of an
      antibiotic-resistant organism in a shorter time than that required to perform
      traditional phenotypic susceptibility testing. Its characteristics are ideal for
      implementation in a kit form.

PMID- 11592650
TI  - Spectrophotometric bioanalytical flow-injection system for control of
      hemodialysis treatment.
AB  - A spectrophotometric flow-injection analysis (FIA) system for monitoring clinical
      hemodialysis is demonstrated. The role of a dialysate urea detector incorporated
      in this bioanalytical system is played by an optical flow-through biosensor based
      on Prussian Blue film with chemically linked urease forming a monomolecular layer
      of the enzyme. This pH-enzyme optode-FIA system is useful for the selective
      determination of post-dialysate urea in the range of concentration corresponding
      to its level in real clinical samples (2-16 mmol l(-1)). This bioanalytical
      system allows the analysis of about 15 samples of spent dialysate per hour. The
      operational and storage stabilities of the applied biosensor are longer than 2
      weeks and 2 months, respectively. Clinical evaluation of the bioanalytical system
      was performed.

PMID- 11592651
TI  - Real-time monitoring of formaldehyde-induced DNA-lysozyme cross-linking with
      piezoelectric quartz crystal impedance analysis.
AB  - A novel method for monitoring, in real time, the formaldehyde (FA)-induced DNA
      protein cross-linking process with the piezoelectric quartz crystal impedance
      (PQCI) technique is proposed. The method was used to monitor FA-induced DNA
      lysozyme cross-link formation. Lysozyme was directly immobilized on the silver
      electrode surface of a piezoelectric quartz crystal by adsorption. The lysozyme
      coated piezoelectric sensor was in contact with FA and DNA solutions. The time
      courses of the resonant frequency and equivalent circuit parameters of the sensor
      during the cross-linking were simultaneously obtained and are discussed in
      detail. On the basis of the feature of the multi-dimensional information provided
      by the PQCI technique, it was concluded that the observed frequency decrease
      could be mainly ascribed to the mass increase resulting from the cross-linking.
      According to the frequency decrease with time, the kinetics of the cross-linking
      process were quantitatively studied. A piezoelectric response model for the cross
      linking was theoretically derived. Fitting the experimental data to the model,
      the kinetic parameters, such as the binding and dissociation rate constants (k(1)
      and k(-1)) and the cross-linking equilibrium constant (Ka), were determined. At
      37 degrees C, the k(1), k(-1) and Ka values obtained were 7.0 (+/-0.1) x 10(-5)
      (microg ml(-1))(-1) s(-1), 6.6 (+/-0.1) x 10(-3) s(-1) and 1.06 (+/-0.02) x 10(
      2) (microg ml(-1))(-1), respectively.

PMID- 11592653
TI  - Determination of indomethacin polymorphic contents by chemometric near-infrared
      spectroscopy and conventional powder X-ray diffractometry.
AB  - A chemoinfometric method for the quantitative determination of the crystal
      content of indomethacin (IMC) polymorphs, based on Fourier-transform near
      infrared (FT-NIR) spectroscopy, was established. A direct comparison of the data
      with those collected using the conventional powder X-ray diffraction method was
      performed. Pure alpha and gamma forms of IMC were prepared using published
      methods. Powder X-ray diffraction profiles and NIR spectra were recorded for six
      kinds of standard material with various contents of the gamma form of IMC.
      Principal component regression (PCR) analyses were performed on the basis of the
      normalized NIR spectral sets of standard samples with known contents of the gamma
      form of IMC. A calibration equation was determined to minimize the root mean
      square error of the prediction. The predicted gamma form contents were
      reproducible and had a relatively small standard deviation. The values of the
      gamma form contents predicted by the two methods were in close agreement. The
      results indicated that NIR spectroscopy provides an accurate quantitative
      analysis of crystallinity in polymorphs compared with the results obtained by
      conventional powder X-ray diffractometry.

PMID- 11592654
TI  - Microwave treatment of biological samples for methylmercury determination by high
      performance liquid chromatography-cold vapour atomic fluorescence spectrometry.
AB  - A simple and rapid microwave-assisted alkaline digestion procedure was developed
      in combination with high performance liquid chromatography-ultraviolet post
      column oxidation-cold vapour atomic fluorescence spectrometric detection for
      methylmercury determination in biological tissues. Since the stability of
      methylmercury in methanolic potassium hydroxide solution under microwave
      irradiation was verified, the microwave-assisted extraction procedure was
      optimized in terms of quantitative recovery of methylmercury and minimum time
      required. The alkaline extracts were subjected to clean-up steps with
      dichloromethane and hydrochloric acid in order to reduce matrix interferences in
      methylmercury determination. The effects of matrix interferences were checked by
      comparison of the slopes corresponding to calibration and standard addition
      curves. The accuracy of the method was evaluated by the analysis of two
      biological certified reference materials, NRC TORT-2 and BCR 463. The results
      obtained by the proposed method were in good agreement with the certified values
      of methylmercury concentration in both materials. The detection limit was 10
      microg kg(-1) and the relative standard deviation was < 8% for methylmercury
      concentrations ranging from 0.15 to 3.0 mg kg(-1).

PMID- 11592658
TI  - Rapid flow injection spectrophotometric determination of monofluorophosphates in
      toothpastes after on-line hydrolysis by alkaline phosphatase immobilized on a
      cellulose nitrate membrane.
AB  - A new, rapid flow injection (FI) method is reported for the spectrophotometric
      determination of monofluorophosphate (MFP) ions in toothpastes. MFP ions are
      hydrolyzed on-line by alkalinephosphatase (APase) immobilized on a cellulose
      nitrate membrane, prior to injection in the FI system. The yielded orthophosphate
      ions are determined spectrophotometrically (lambda(max) = 690 nm) using the
      molybdenum blue approach. The chemical and FI variables that affected the
      enzymatic reaction were studied and optimized. A study of interferences was also
      carried out. The proposed method is very precise (s(r) = 0.7% at 1.0 x 10(-4) mol
      l(-1) MFP, n = 12), fast (sampling rate of 72 h(-1)) and allows the determination
      of MFP ions in the range of 4.0 x 10(-5) to 6.0 x 10(-4) mol l(-1) with a
      satisfactory 3sigma detection limit of 4.0 x 10(-6) mol l(-1). The application of
      the proposed FI method to toothpaste samples yielded accurate results (e(r) <
      2.0%) compared with a potentiometric reference procedure.

PMID- 11592660
TI  - Pathway HUDs: are they viable?
AB  - We describe two experiments that examine 3D pathway displays in a head-up
      location for aircraft landing and taxi. We address both guidance performance and
      pilot strategies in dividing, focusing, and allocating attention between flight
      path information and event monitoring. In Experiment 1 the 3D pathway head-up
      display (HUD) was compared with a conventional 2D HUD. The former was found to
      produce better guidance, with few costs to event detection. Some evidence was
      provided that attentional tunneling of the pathway HUD inhibits the detection of
      unexpected traffic events. In Experiment 2, the pathway display was compared in a
      head-up versus a head-down location. Excellent guidance was achieved in both
      locations. A slight HUD cost for vertical tracking in the air was offset by a HUD
      benefit for event detection and for lateral tracking during taxi (i.e., on the
      ground). The results of both experiments are interpreted within the framework of
      object- and space-based theories of visual attention and point to the conclusion
      that pathway HUDs combine the independent advantages of pathways and HUDs,
      particularly during ground operations. Actual or potential applications include
      understanding the costs and benefits of positioning a 3D pathway display in a
      head-up location.

PMID- 11592661
TI  - Visual search for traffic signs: the effects of clutter, luminance, and aging.
AB  - Latency and eye movement measures were used to examine the effects of aging,
      clutter, and luminance on visual search for traffic signs embedded in digitized
      images of driving scenes. Initially 14 older and 14 younger observers classified
      daytime and nighttime traffic scenes as containing low or high amounts of
      clutter. Next, an independent sample of 14 younger and 14 older participants
      searched for traffic signs contained within these scenes. Errors were more common
      among the elderly. Search efficiency declined with increased clutter and with
      aging. However, relative to the young, older adults did not suffer
      disproportionately as a result of increased clutter. The methods developed might
      be profitably employed to assess sign conspicuity and sign acquisition during
      driving.

PMID- 11592662
TI  - Asymmetric performance in the cocktail party effect: implications for the design
      of spatial audio displays.
AB  - An experiment was conducted to determine the extent to which hemispheric
      specialization is manifested in the performance of tasks in which listeners are
      required to attend to one of several simultaneously spoken speech communications.
      Speech intelligibility and response time were measured under factorial
      combinations of the number of simultaneous talkers, the target talker hemifield,
      and the spatial arrangement of talkers. Intelligibility was found to be mediated
      by all of the independent variables. Results are discussed in terms of the design
      of adaptive spatial audio interfaces for speech communications. Actual or
      potential applications of this research include the design of adaptive spatial
      audio interfaces for speech communications.

PMID- 11592663
TI  - Use of warnings in an attentionally demanding detection task.
AB  - The study assessed the use of binary warnings in a detection task with high
      attentional demands. Participants in the experiment had to decide whether to
      continue or halt production based on a briefly displayed number that indicated a
      temperature level. The short time that the number was displayed required that
      participants focus on the display area. Participants were rewarded for production
      when the system was intact and were heavily penalized for decisions to produce
      under dangerous temperature levels. Color-coded warning cues (green for safe, red
      for danger) were displayed to the participants prior to number presentation. The
      experimental conditions differed in the validity of the cue and in the
      probability of red cues. Results showed significant learning for all conditions.
      Participants tended to ignore the nonvalid and low-validity cues and rely only on
      highly valid cues. However, the mere existence of cues affected participants'
      general tendency to take risks. Actual or potential applications of this research
      include improving systems that require operators to devote attention to complex
      tasks while receiving and responding to warnings.

PMID- 11592664
TI  - Information order and outcome framing: an assesment of judgment bias in a
      naturalistic decision-making context.
AB  - Findings that decision makers can come to different conclusions depending on the
      order in which they receive information have been termed the "information order
      bias." When trained, experienced individuals exhibit similar behaviors; however,
      it has been argued that this result is not a bias, but rather, a pattern-matching
      process. This study provides a critical examination of this claim. It also
      assesses both experts' susceptibility to an outcome framing bias and the effects
      of varying task loads on judgment. Using a simulation of state-of-the-art ship
      defensive systems operated by experienced, active-duty U.S. Navy officers, we
      found no evidence of a framing bias, while task load had a minor, but systematic
      effect. The order in which information was received had a significant impact,
      with the effect being consistent with a judgment bias. Nonetheless, we note that
      pattern-matching processes, similar to those that produce inferential and
      reconstructive effects on memory, could also explain our results. Actual or
      potential applications of this research include decision support system
      interfaces or training programs that might be developed to reduce judgment bias.

PMID- 11592665
TI  - Incidental memory and navigation in panoramic virtual reality for electronic
      commerce.
AB  - Recently much effort has been dedicated to designing and implementing World Wide
      Web sites for virtual shopping and e-commerce. Despite this effort, relatively
      little empirical work has been done to determine the effectiveness with which
      different site designs sell products. We report three experiments in which
      participants were asked to search for products in various experimental e-commerce
      sites. Across the experiments participants were asked to search in either QTVR
      (QuickTime Virtual Reality), hypertext, or pictorially rich hypertext
      environments; they were then tested for their ability to recall the products seen
      and to recognize product locations. The experiments demonstrated that when using
      QTVR (Experiments 1, 2, and 3) or pictorial environments (Experiment 2),
      participants retained more information about products that were incidental to
      their goals. In two of the experiments it was shown that participants navigated
      more efficiently when using a QTVR environment. The costs and benefits of using
      3D virtual environments for on-line shops are discussed. Actual or potential
      applications of this research include support for the development of e-commerce
      design guidelines.

PMID- 11592666
TI  - Management by consent in human-machine systems: when and why it breaks down.
AB  - This study examined the effects of conflict type, time pressure, and display
      design on operators' ability to make informed decisions about proposed machine
      goals and actions in a management-by-consent context. A group of 30 B757 pilots
      were asked to fly eight descent scenarios while responding to a series of air
      traffic control clearances. Each scenario presented pilots with a different
      conflict that arose from either incompatible goals contained in the clearance or
      inappropriate implementation of the clearance by automated flight deck systems.
      Pilots were often unable to detect these conflicts, especially under time
      pressure, and thus failed to disallow or intervene with proposed machine actions.
      Detection performance was particularly poor for conflicts related to clearance
      implementation. These conflicts were most likely to be missed when automated
      systems did more than the pilot expected of them. Performance and verbal protocol
      data indicate that the observed difficulties can be explained by a combination of
      poor system feedback and pilots' difficulties with generating expectations of
      future system behavior. Our results are discussed in terms of their implications
      for the choice and implementation of automation management strategies in general
      and, more specifically, with respect to risks involved in envisioned forms of
      digital air-ground communication in the future aviation system. Actual or
      potential applications of this research include the design of future data link
      systems and procedures, as well as the design of future automated systems in any
      domain that rely on operator consent as a mechanism for human-machine
      coordination.

PMID- 11592667
TI  - Menu design with visual momentum for compact smart products.
AB  - Users of compact smart products with small screens often have trouble learning
      the menu structure. If they cannot master the menu structure, users are not able
      to fully utilize the products. It is argued in this paper that using visual
      momentum in menu representation design helps users develop effective mental maps
      of menu structures and promotes learning of the user interface. To assess the
      effect of visual momentum in this study, four types of menu representations were
      developed. Additionally, two menu hierarchies, two types of function key layout,
      and two types of function key labeling were assessed to examine the effects of
      menu dimension and compatibility. Experimental results indicated that
      participants using a partial menu map with visual momentum design performed the
      best, and participants using a partial menu map without visual momentum performed
      the poorest, even worse than those-using command-only representation. The results
      also showed that the menu navigation problem appeared to be particularly
      significant with a deep menu hierarchy. Actual or potential applications of this
      research include menu representation design for compact smart products.

PMID- 11592668
TI  - Haptic force-feedback devices for the office computer: performance and
      musculoskeletal loading issues.
AB  - Pointing devices, essential input tools for the graphical user interface (GUI) of
      desktop computers, require precise motor control and dexterity to use. Haptic
      force-feedback devices provide the human operator with tactile cues, adding the
      sense of touch to existing visual and auditory interfaces. However, the
      performance enhancements, comfort, and possible musculoskeletal loading of using
      a force-feedback device in an office environment are unknown. Hypothesizing that
      the time to perform a task and the self-reported pain and discomfort of the task
      improve with the addition of force feedback, 26 people ranging in age from 22 to
      44 years performed a point-and-click task 540 times with and without an
      attractive force field surrounding the desired target. The point-and-click
      movements were approximately 25% faster with the addition of force feedback
      (paired t-tests, p < 0.001). Perceived user discomfort and pain, as measured
      through a questionnaire, were also smaller with the addition of force feedback (p
      < 0.001). However, this difference decreased as additional distracting force
      fields were added to the task environment, simulating a more realistic work
      situation. These results suggest that for a given task, use of a force-feedback
      device improves performance, and potentially reduces musculoskeletal loading
      during mouse use. Actual or potential applications of this research include human
      computer interface design, specifically that of the pointing device extensively
      used for the graphical user interface.

PMID- 11592669
TI  - Effect of computer keyboard slope and height on wrist extension angle.
AB  - The goal of this study was to determine the systematic effect that varying the
      slope angle of a computer keyboard along with varying keyboard height (relative
      to elbow height) have on wrist extension angle while typing. Thirty participants
      typed on a keyboard whose slope was adjusted to +15 degrees, +7.5 degrees, 0
      degrees, -7.5 degrees, and -15 degrees. The height of the keyboard was set up
      such that participants' wrists were at the same height as their elbows, above
      their elbows, and four cm below their elbows. Results showed that as keyboard
      slope angle moved downward from +15 degrees to -15 degrees, mean wrist extension
      decreased approximately 13 degrees (22 degrees at +15 degrees slope to 9 degrees
      at -15 degrees slope). Keyboard height had a similar effect with mean wrist
      extension decreasing from 21.8 degrees when the keyboard was lower than elbow
      height, to 7.3 degrees when the keyboard was higher than elbow height. Potential
      application of this research includes the downward sloping of computer keyboards,
      which could possibly be beneficial in the prevention of musculoskeletal disorders
      affecting the wrist.

PMID- 11592670
TI  - Auditory localization under sustained +Gz acceleration.
AB  - The ability to localize a virtual sound source in the horizontal plane was
      evaluated under varying levels of sustained (+Gz) acceleration. Participants were
      required to judge the locations of spatialized noise bursts in the horizontal
      plane (elevation 0 degrees) during exposure to 1.0, 1.5, 2.5, 4.0, 5.5, and 7.0
      +Gz. The experiment was conducted at the U.S. Air Force Research Laboratory's
      Dynamic Environment Simulator, a three-axis centrifuge. No significant increases
      in localization error were found between 1.0 and 5.5 +Gz; however, a significant
      increase did occur at the 7.0 +Gz level. In addition, the percentage of
      front/back confusions did not vary as a function of +Gz level. Collectively,
      these results indicate that the ability to localize virtual sound sources is well
      maintained at various levels of sustained acceleration. Actual or potential
      applications include the incorporation of spatial audio displays into the human
      computer interface for vehicles that are operated in acceleration environments.

PMID- 11592671
TI  - The influence of stimulants, sedatives, and fatigue on tunnel vision: risk
      factors for driving and piloting.
AB  - A computerized task was used in two studies to examine the influence of
      stimulants, sedatives, and fatigue on single-target and divided-attention
      responses in different parts of the visual field. The drug effects were evaluated
      over time with repeated behavioral and subjective measures against ascending and
      descending drug levels. In the first study, 18 fully rested participants received
      placebo, alprazolam (0.5 mg), and dextroamphetamine (10 mg). Alprazolam impairs
      performance, whereas dextroamphetamine induces enhancement and tunnel vision.
      Study 2 exposed 32 participants to fatigue and no fatigue with a repeated
      measures crossover design. Four independent groups subsequently received placebo,
      dextroamphetamine (10 mg), caffeine (250 mg), or alcohol (.07%). Under fatigue,
      stimulants have no performance-enhancing effects, whereas impairment from alcohol
      is severe. Under no fatigue, alcohol has a modest effect, caffeine has no effect,
      and dextroamphetamine significantly enhances divided-attention performance
      coincident with tunnel vision. Participants rate all drug effects more
      stimulating and less sedating while fatigued. Implications for transportation
      safety are discussed. Actual or potential applications of this research include
      driver and pilot training.

PMID- 11592672
TI  - Multichannel auditory search: toward understanding control processes in
      polychotic auditory listening.
AB  - Two experiments are presented that serve as a framework for exploring auditory
      information processing. The framework is referred to as polychotic listening or
      auditory search, and it requires a listener to scan multiple simultaneous
      auditory streams for the appearance of a target word (the name of a letter such
      as A or M). Participants' ability to scan between two and six simultaneous
      auditory streams of letter and digit names for the name of a target letter was
      examined using six loudspeakers. The main independent variable was auditory load,
      or the number of active audio streams on a given trial. The primary dependent
      variables were target localization accuracy and reaction time. Results showed
      that as load increased, performance decreased. The performance decrease was
      evident in reaction time, accuracy, and sensitivity measures. The second study
      required participants to practice the same task for 10 sessions, for a total of
      1800 trials. Results indicated that even with extensive practice, performance was
      still affected by auditory load. The present results are compared with findings
      in the visual search literature. The implications for the use of multiple
      auditory displays are discussed. Potential applications include cockpit and
      automobile warning displays, virtual reality systems, and training systems.

PMID- 11592673
TI  - A comparative atomic force microscopy study on living skin fibroblasts and liver
      endothelial cells.
AB  - Atomic force microscopy (AFM) has been used to image a wide variety of cells and
      has proven to be successful in cellular imaging, by comparing results obtained by
      AFM with SEM or TEM. The aim of the present study was to investigate further the
      conditions for AFM imaging of living cells and compare the results with those
      obtained by SEM. We chose to image skin fibroblast and liver sinusoidal
      endothelial cells of two different sources, because these cells have been well
      described and characterized in earlier studies. AFM imaging of living cells
      mainly reveals submembranous structures, which could not be observed by SEM. This
      concerns the visualization of the overall cytoskeletal architecture and
      organelles, without the necessity of any preparative steps. The AFM study of
      living cells allows a time lapse study of dynamic changes of the actin
      cytoskeleton under the influence of the cytoskeleton-disturbing drug cytochalasin
      B in cells that can be followed individually during the process. However, softer
      samples, such as the fenestrated parts of living rat liver sinusoidal endothelial
      cells in culture could not be visualized. Apparently, these cell parts are
      disrupted due to tip-sample interaction in contact mode. To avoid the lateral
      forces and smearing artefacts of contact mode AFM, non-contact imaging was
      applied, resulting in images of higher quality. Still, endothelial fenestrae
      could not be visualized. In contrast, contact imaging of immortomouse liver
      sinusoidal endothelial cells, which are devoid of fenestrae, could easily be
      performed and revealed a detailed filamentous cytoskeleton.

PMID- 11592674
TI  - Prospects of atomic resolution imaging with an aberration-corrected STEM.
AB  - We investigated high-resolution scanning transmission electron microscope (STEM)
      images obtained from a microscope equipped with a spherical aberration corrector.
      The probe size (full-width at half-maximum) is reduced to 0.76 A at 200 kV by
      assuming the fifth-order spherical aberration coefficient C5 = 100 mm. For the
      simulation we have used the recently developed scheme for a STEM image simulation
      based on the Fast Fourier Transform (FFT) multislice algorithm. The peak-to
      background (P/B) ratio of the high-angle annular dark-field (HAADF) image is
      significantly improved at a thin specimen region. Although the P/B ratio becomes
      worse at a thicker region, the resolution is kept high even at such a region. An
      almost true HAADF signal will be obtained even from a weak-scattering phosphorous
      column in InP [001] when the background is subtracted. In the bright-field image
      the coherent character of elastic scattering is suppressed by averaging over a
      large convergence angle, making the specimen effectively self-luminous. The claim
      that HAADF imaging is relatively insensitive to a defocus as well as a specimen
      thickness is valid only qualitatively, and a detailed image simulation will be
      required for a quantitative analysis as in the case of the conventional
      transmission electron microscope. It was noted that the delta function
      approximation for the object function may not be applicable for a very fine
      probe, and that the achievable resolution of the HAADF imaging will be limited by
      the widths of the high-angle thermal diffuse scattering potential.

PMID- 11592675
TI  - Light element analysis in oxycarbonate superconductors using EELS.
AB  - Elemental analysis in an oxycarbonate superconductor ((Cu,N,C)Sr2CaCu2Oy) is
      conducted using transmission electron microscope-electron energy-loss
      spectroscopy with detector-gain correction. The gain correction enables highly
      sensitive elemental analysis and precise measurement of energy-loss near edge
      structures (ELNESs). It is found that carbon is included as a CO3 group, because
      the carbon K-edge in the oxycarbonate shows the same ELNES observed from CaCO3.
      Nitrogen ELNES is similar to that of Sr(NO3)2, so nitrogen is contained as a NO3
      group. Although both CO3(2-) and NO3- have similar planar atomic arrangements,
      the nitrogen ELNES observed is different from that of carbon. EEL spectrum
      simulation based on DV-Xalpha method is used to interpret the difference.

PMID- 11592676
TI  - The structure of Si nanocrystals on SiC.
AB  - Si nanocrystals grown on cubic SiC have been characterized using high-resolution
      transmission electron microscopy. At lower temperatures nanocrystals grow in two
      different orientations, whereas at higher temperatures they grow in a single
      preferred orientation. The nanocrystals are shown to be unstrained; in some cases
      possibly due to the presence of a thin amorphous wetting layer.

PMID- 11592677
TI  - A method for characterizing carbon nanotubes.
AB  - High-resolution transmission electron microscopy and electron energy-loss
      spectroscopy of a multi-walled carbon nanotube (MWCNT) at elevated temperatures
      were studied. Although the observation was carried out at 200 kV, the crystal
      structures of the MWCNT were observed without introducing defects. In addition,
      contamination on the MWCNT, such as nanobubbles, was removed during the
      observation at 600 degrees C. In this paper, we report the observation conditions
      and experimental results. The experimental results obtained both at 600 degrees C
      and at room temperature were compared.

PMID- 11592678
TI  - Applying secondary ion mass spectrometry to the analysis of elements in goblet
      cells of conjunctiva.
AB  - We investigated the location of elements in the goblet cells of rat conjunctiva
      by analyzing ion images produced by secondary ion mass spectrometry (SIMS) and
      comparing them with those produced by energy dispersive X-ray analyser (EDX).
      Conjunctivas of normal Spraque-Dawley rats were quenched in propane prechilled
      liquid nitrogen. Semi-thin sections were made with a cryo-ultramicrotome, freeze
      dried, carbon-coated and observed under a light microscope, SIMS and scanning
      electron microscope (SEM). In the element analysis by SIMS, images of positive
      ions were examined with an O2+ primary ion source and images of negative ions
      with a Ga+ ion source. The same sections were observed and analysed with SEM-EDX.
      Morphological features and images of elements with SIMS and EDX were compared.
      Na, Mg, K, and Ca were detected as positive ions and OH, CN, P, S, and Cl as
      negative ions with SIMS, but C, N, O, Na, Mg, P, S, Cl, K, and Ca were detected
      with EDX. The spatial resolution of SIMS in element location was higher than that
      of EDX. Many elements were clearly located in the goblet cells on ion images by
      SIMS. Element ion images were demonstrated more densely in goblet cells than in
      other parts within conjunctiva and by SIMS compared to EDX. SIMS is a useful
      method for the detection of elements and their locations in ocular tissues and
      cells.

PMID- 11592679
TI  - The osteoblastic phenotype in calcium-depleted and calcium-repleted rats: a
      structural and histomorphometric study.
AB  - In a previous report we showed that young rats fed a calcium-free diet for 28
      days developed severe hypocalcaemia and showed a significant increase in serum
      alkaline phosphatase activity. The main histological and cytochemical changes
      exhibited by these animals in bone of the metaphyseal primary spongiosa were: (1)
      hyperplasia of osteoblasts, (2) an increase in the frequency of tartrate
      resistant acid phosphatase (TRAP)-positive osteoblasts apposed to osteoid, and
      (3) an excessive amount of osteoid tissue. In addition to typical osteoblasts,
      there was a subpopulation of osteoblast-like cells with coated pits, lysosome
      like bodies and large cytoplasmic processes. In the present study, we
      investigated how the above parameters change when calcium-depleted rats are
      placed on a normal diet for 7 days. Such a regimen normalized calcium
      concentration and alkaline phosphatase activity in the serum. The osteoid
      thickness returned to normal and, in some areas, was fully calcified. Most
      osteoblasts no longer showed TRAP activity and their ultrastructure was similar
      to that found in controls. Despite an intense alkaline phosphatase activity, some
      of them still exhibited a number of macrophagic characteristics. They were TRAP
      positive, and showed electron-dense bodies in the cytoplasm facing bone, an
      abundance of coated pits, calcified spicules impinging on the cell membrane and
      large processes extending into the mineralized matrix. We concluded that calcium
      deficiency causes hyperplasia of osteoblasts in primary spongiosa and an increase
      in expression of TRAP. It also induces changes in their phenotype characterized
      by the acquisition of macrophagic cellular features. While TRAP activity is
      normalized by calcium repletion, macrophagic characteristics persist. These
      results suggest that the osteoblast can modulate its phenotype according to its
      physiological status.

PMID- 11592680
TI  - Swelling of capillary endothelial cells and cardiomyocytes in the ischaemic
      myocardium of artificially arrested canine hearts.
AB  - To establish whether coronary perfusion with cardioplegic solutions results in
      better intraischaemic structural preservation of endothelial cells than of
      cardiomyocytes, we determined intraischaemic swelling of these two cell types in
      hearts differently arrested during global ischaemia at 5 degrees C. Cardiac
      arrest was induced in situ by aortic cross clamping or by additional coronary
      perfusion with various cardioplegic solutions. Parameters for cellular swelling
      were determined, i.e. barrier thickness of capillary endothelial cells and sum of
      the volume fractions (V(V)) of free sarcoplasm and mitochondria (V(VSp) + V(VMi))
      in cardiomyocytes. In order to test the intraischaemic relative increase of
      cellular volume in both cell types, regression analyses were performed. The
      results show that the relative intraischaemic volume increase was similar in both
      cell types after perfusion with histidine-tryptophan-ketoglutarate solution, and
      significantly less pronounced in capillary endothelial cells after perfusion with
      University of Wisconsin solution. In hearts arrested with St. Thomas' Hospital
      solution, a significantly higher volume increase was determined in capillary
      endothelial cells. Thus, capillary endothelium does not generally show a higher
      structural preservation than cardiomyocytes during ischaemia. Instead, volume
      regulation in both types of cells depends on the type of cardioplegic solution
      used. These results should be taken into consideration in human transplantation
      medicine.

PMID- 11592681
TI  - Suppressed localization of a major autolysin on Staphylococcus aureus treated
      with tetracycline.
AB  - Surface localization of a major autolysin (atl gene product, ATL) on
      Staphylococcus aureus treated with tetracycline (TC, 4MIC: 1.56 microg ml(-1))
      was examined using the protein A-gold labelling method. No labelling was noted on
      the surface of the next septal region, but it was observed on the previous septal
      region. In contrast, on untreated cells the gold particles were found not only
      along the septal surface, but also on the next septal region. These findings
      agree with those obtained from both ultrathin and whole-mount specimens,
      indicating that TC inhibits the localization of ATL in the next septal region.
      They further support the suggestion that ATL localization on the cell surface is
      closely associated with the cell cycle. When S. aureus was treated with otherwise
      lytic concentrations of penicillin G (PCG, 4MIC: 0.02 microg ml(-1)) in the
      presence of TC, the distribution of the label on the cell surface was found to be
      very similar to that on the TC-treated organisms. This suggests that the
      inhibitory effect of TC on PCG-induced lysis was not due to complete loss of ATL
      on the cell surface but instead to inhibition of ATL localization in the next
      septal region.

PMID- 11592682
TI  - Localization of receptor activator of NFkappaB ligand, RANKL, in periodontal
      tissues during experimental movement of rat molars.
AB  - The receptor activator of NFkappaB ligand, RANKL, is one of the key regulatory
      molecules in osteoclast formation and function. We examined RANKL localization in
      the periodontal tissues during experimental movement of rat molars. To produce
      orthodontic force, an elastic band was inserted between the upper first and
      second molars for 4 days, and the dissected maxillae were subjected to light and
      electron microscopic immunocytochemical examination for RANKL. Expression of
      RANKL protein was detected in osteoblasts, osteocytes, fibroblasts, and
      osteoclasts mostly located in resorption lacunae. In osteoblasts, osteocytes, and
      fibroblasts, RANKL localization was mainly observed in the cytoplasm, the
      cisternae of rough endoplasmic reticulum and along plasma membranes. In
      osteoclasts, RANKL was expressed along the ruffled, border membranes and in the
      cytoplasm, including the clear zone. These results suggest that during tooth
      movement, osteoclast differentiation and activation are regulated, at least in
      part, by RANKL, possibly produced by osteoblasts/stromal cells and osteoclasts
      themselves in the periodontal tissues.

PMID- 11592683
TI  - New analytical techniques in food science.
AB  - In this review, some of the latest analytical techniques that are being used for
      the study and characterization of food are examined. This work intends to provide
      an updated overview (including works published up to June 1999) on the principal
      applications of such techniques together with their main advantages and drawbacks
      in food analysis. Some future developments of these systems and their foreseeable
      application in food characterization are also discussed. The reviewed techniques
      are those based on spectroscopic, biological, separation, and electrochemical
      procedures. Moreover, some relevant facts on new systems for sample preparation
      and on-line couplings are also given.

PMID- 11592684
TI  - Advances in the development of functional foods from buckwheat.
AB  - Buckwheat originated in North or East Asia and is widely adapted in North
      America. It has been grown since at least 1000 BC in China. It has very strong
      adaptability to adverse environments with a very short growing span. Many
      varieties are growing around the world, but mainly in the north hemisphere.
      Currently the most common buckwheat spice is Fagopyrum esculentum Moench (common
      buckwheat or sweet buckwheat), while Fagopyrum tartaricum is also available in
      some mountainous regions. Many nutraceutical compounds exist in buckwheat seeds
      and other tissues. Buckwheat has been used and will be better used as an
      important raw material for functional food production. In this review we focus on
      works related to the development of functional foods from common buckwheat,
      Fagopyrum esculentum Moench. A lot of research has be conducted in the
      functionalities and properties of buckwheat proteins, flavonoids, flavones,
      phytosterols, thiamin-binding proteins, and other rare compounds in buckwheat
      seeds. Buckwheat proteins have unique amino acid composition with special
      biological activities of cholesterol-lowering effects, antihypertensition
      effects, and improving the constipation and obisity conditions by acting similar
      as to dietary fiber and interrupting the in vivo metabolisms. The trypsin
      inhibitors isolated from buckwheat seeds are heat stable and can cause poor
      digestion if they are not suitably cooked before consumption. The allergenic
      proteins existing in the buckwheat seeds and their derivatives were reviewed with
      respect to their chemical and biochemical characteristics as well as the
      physiological reactions after digestion. Some possible mechanisms involved in
      these effects are discussed in this review. Experiments, both with animal models
      and with human beings, revealed that buckwheat flour can improve diabetes,
      obesity, hypertension, hypercholesterolemia and constipation. Methods to exploit
      buckwheat seeds and flour to produce highly effective nutraceuticals are also
      reviewed.

PMID- 11592685
TI  - Issues in the substantiation process of health claims.
AB  - Attempts are being made at the international level within the framework of the
      Codex Alimentarius to establish guidelines for health claims. An important issue
      that has to be addressed is the process of substantiating any health claim.
      Previous papers have addressed aspects relating to the development and regulatory
      control of functional foods and certain issues relating to claims. This paper
      addresses several issues concerning the substantiation of health claims through
      the examination of the regulations and guidelines in several countries. They
      include (1) importance of human- and product-based studies; (2) concept of
      scientific consensus; (3) authorization of claim wording; (4) availability of
      scientific evidence to public (confidentiality). The paper finally proposes a
      system based on generic and innovative health claims.

PMID- 11592686
TI  - Gelatin: a valuable protein for food and pharmaceutical industries: review.
AB  - Many works have appeared in various scientifically reputable journals and
      publications worldwide that seem to have made potential or satisfactory
      contribution to our knowledge on the functions and utilization of gelatin--an
      important source of animal protein. Irrespective of these worldwide publications,
      room still exists for more work to be done to fully understand the utilization,
      chemical, biological, physical and functional properties of gelatin. Chemical and
      enzymatic modifications as well as biological studies should be undertaken with
      accuracy to be able to extend the utilization of gelatin in food and
      pharmaceuticals.

PMID- 11592687
TI  - Fluid phase and receptor-mediated endocytosis in Paramecium primaurelia by
      fluorescence confocal laser scanning microscopy.
AB  - In ciliated protozoa, most nutrients are internalized via phagocytosis by food
      vacuole formation at the posterior end of the buccal cavity. The uptake of small
      sized molecules and external fluid through the plasma membrane is a localized
      process. That is because most of the cell surface is internally covered by an
      alveolar system and a fibrous epiplasm, so that only defined areas of the cell
      surface are potential substance uptake sites. The purpose of this study is to
      analyze, by fluorescence confocal laser scanning microscopy, the relationship
      between WGA (Triticum vulgaris agglutinin) and dextran internalization in
      Paramecium primaurelia cells blocked in the phagocytic process, so that markers
      could not be internalized via food vacuole formation. WGA, which binds to surface
      constituents of fixed and living cells, was used as a marker for membrane
      transport and dextran as a marker for fluid phase endocytosis. After 3 min
      incubation, WGA-FITC is found on plasma membrane and cilia, and successively
      within small cytoplasmic vesicles. After a 10-15 min chase in unlabeled medium,
      the marked vesicles decrease in number, increase in size and fuse with food
      vacuoles. This fusion was evidenced by labeling food vacuoles with BSA-Texas red.
      Dextran enters the cell via endocytic vesicles which first localize in the
      cortical region, under the plasma membrane, and then migrate in the cytoplasm and
      fuse with other endocytic vesicles and food vacuoles. When cells are fed with WGA
      FITC and dextran-Texas red at the same time, two differently labeled vesicle
      populations are found. Cytosol acidification and incubation in sucrose medium or
      in chlorpromazine showed that WGA is internalized via clathrin vesicles, whereas
      fluid phase endocytosis is a clathrin-independent process.

PMID- 11592688
TI  - An atomic force microscopy investigation of protein crystal surface topography.
AB  - Tapping mode atomic force microscopy was employed to study the surface structure
      of different protein crystals in a liquid environment. The (101) face of hen egg
      white lysozyme crystals and the (111) face of horse spleen ferritin crystals were
      studied. On the (101) face of lysozyme crystals we observed islands delimitated
      by micro-steps and elongated in the [010] direction. The elongation direction
      coincides with the preferential growth direction predicted by a growth model
      reported in the literature. The islands observed on the ferritin (111) face are
      also delimitated by micro-steps but have circular symmetry. Sectioning of the
      images allowed us to measure the step heights. The surface free energy was
      estimated from the growth step morphology. Molecular resolution was achieved for
      ferritin crystals, showing a hexagonal surface packing, as expected for the
      molecular lattice of a (111) face in a fcc crystal.

PMID- 11592689
TI  - Dynamical transition of myoglobin in a crystal: comparative studies of X-ray
      crystallography and Mossbauer spectroscopy.
AB  - The crystallographic normal mode refinements of myoglobin at a wide range of
      temperature from 40 K to 300 K were carried out to study the temperature
      dependence of the internal atomic fluctuations. The refinement method decomposes
      the mean square displacement from the average position, (deltar2), into the
      contributions from the internal degrees of freedom and those from the external
      degrees of freedom. The internal displacements show linear temperature dependence
      as (deltar2)=alphaT+beta, throughout the temperature range measured here, and
      exhibit no obvious change in the slope alpha at the dynamical transition
      temperature (Tc=ca. 180 K). The slope alpha is practically the same as the value
      predicted theoretically by normal mode analysis. Such linear dependence is
      considered to be due to the following reason. The crystallographic Debye-Waller
      factor represents the static distribution caused by convolution of temperature
      dependent normal mode motions and a temperature-independent set of the
      conformational substates. In contrast, Mossbauer absorption spectroscopy shows a
      clear increase in the gradient alpha at Tc. This difference from X-ray
      diffraction originates from the incoherent nature of the Mossbauer effect
      together with its high-energy resolution, which yields the self-correlation, and
      the temporal behavior of individual Fe atoms in the myoglobin crystal.

PMID- 11592690
TI  - Molecular dynamics simulation of n-dodecyl phosphate aggregate structures.
AB  - Aggregates of n-dodecyl phosphate present an attractive model system of simple
      phospholipid amphiphile supramolecular structures for study by molecular dynamics
      simulation, since these systems have previously been studied experimentally under
      various conditions. A detailed molecular dynamics description of the properties
      of planar bilayer membranes (as a model for unilamellar vesicular membranes) and
      spherical micelles under various simulated conditions is presented. It is shown
      that the united-atom model of GROMOS96 applying the force-field parameter set
      43A2 for biomolecular systems yields properties in agreement with experimental
      ones in most cases. Hydrogen bonding plays a role in stabilizing the bilayer
      aggregates at low pH, but not for the micelles, which are energetically favoured
      at high pH. NMR -S(CD) order parameters for a lipid bilayer system, the diffusion
      of amphiphiles within aggregates and of counterions, and lifetimes of hydrogen
      bonds between amphiphiles and to water are estimated from the MD simulations.

PMID- 11592691
TI  - Chlorophyll transition dipole moment orientations and pathways for flow of
      excitation energy among the chlorophylls of the major plant antenna, LHCII.
AB  - We have attempted in this work an assignment of the Qy dipole moment orientations
      for all the chlorophylls in the major plant antenna, light-harvesting complex II
      (LHCII). Information that has recently become available through a structural
      model of the LHCII, site-directed mutagenesis, and spectroscopy of both LHCII and
      CP29 has been evaluated to model the electronic excited state structure in the
      presence of chlorophyll-chlorophyll and chlorophyll-protein interactions. An
      assignment has been obtained which satisfactorily reproduces the polarized linear
      absorption characteristics. The assignment proposed has also been found to be
      adequate in reproducing the time scales of the energy transfer processes. The
      pathways for the flow of excitation energy among the chlorophylls of the complex
      have been suggested in the context of identity and orientation assignments.

PMID- 11592692
TI  - Hetero-association of caffeine and aromatic drugs and their competitive binding
      with a DNA oligomer.
AB  - NMR spectroscopy has been used to elucidate the molecular basis of the action of
      caffeine (CAF) on the complexation with DNA of mutagens such as ethidium bromide,
      propidium iodide, proflavine and acridine orange, and anticancer drugs such as
      actinomycin D and daunomycin. The hetero-association of CAF and each of the
      aromatic ligands in 0.1 mol L(-1) phosphate buffer (pD=7.1) has been investigated
      as a function of concentration and temperature by 500 MHz 1H NMR spectroscopy and
      analysed in terms of a statistical-thermodynamic model, in which molecules form
      indefinite aggregates for both self-association and hetero-association. The
      analysis leads to determination of the equilibrium constants of hetero
      association and to the values of the limiting chemical shifts of the
      heteroassociation of CAF with each of the aromatic molecules. The hetero
      association constants between CAF and each of the aromatic drugs/dyes are found
      to be intermediate in magnitude between those for self-association of CAF and the
      corresponding drug/dye. The most probable structures of the 1:1 CAF + ligand
      hetero-association complexes have been determined from the calculated values of
      the induced limiting chemical shifts of the drug protons. Knowledge of the
      equilibrium constants for self-association of CAF and the aromatic ligands, for
      their hetero-association and their complexation with a DNA fragment, the
      deoxytetranucleotide 5'-d(TpGpCpA), enabled the relative content of each of the
      CAF-ligand and CAF-ligand-d(TGCA) complexes to be calculated as a function of CAF
      concentration in mixed solutions. It is concluded that, on addition of CAF to the
      solution, the decrease in binding of drug or mutagen with DNA is due both to
      competition for the binding sites by CAF and the aromatic molecules, and to
      formation of CAF-ligand hetero-association complexes in the mixed solution; the
      relative importance of each process depends on the drug or mutagen being
      considered.

PMID- 11592693
TI  - EPR studies of iso-1-cytochrome c: effect of temperature on two-component spectra
      of spin label attached to cysteine at positions 102 and 47.
AB  - Wild-type iso-1-cytochrome c from Saccharomyces cerevisiae containing naturally
      occurring cysteine at position 102 and mutated protein S47C (derived from the
      protein in which C102 had been replaced by threonine) were labeled with cysteine
      specific methanethiosulfonate spin label. Continuous wave (CW) electron
      paramagnetic resonance (EPR) was used to examine the effect of temperature on the
      behavior of the spin label in the oxidized and reduced forms of wild-type
      cytochrome c and in the oxidized form of the mutated protein. The computer
      simulations revealed that the CW EPR spectrum for each form of cytochrome c
      consists of at least two components [a fast (F) and a slow (S) component], which
      differ in the values of the rotational correlation times tauRparallel
      (longitudinal rotational correlation time) and tauRperpendicular (transverse
      rotational correlation time) and that the relative contributions of the F and S
      components of the spectra change with temperature. In addition, the values of the
      rotational correlation times (tauRparallel and tauRperpendicular) for the F
      component appear to change much more dramatically with the temperature than the
      respective values for the S component. A large difference between the behavior of
      the oxidized and reduced wild-type spin-labeled cytochromes c indicates that the
      temperature-induced unfolding of the protein in the region around C102 progresses
      more rapidly when cytochrome c is in the oxidized form.

PMID- 11592694
TI  - On the validity of the two-cells model in the analysis of passive electrical
      properties of gap-junction connected cells.
AB  - It is a rather extended practice to derive electrophysiological data (membrane
      and contact conductances) from experimental data for gap-junction tissues
      assuming that electrical connections are reduced to cell pairs. It is here shown
      that, if the length constant is sufficiently large, the mentioned procedure can
      lead to qualitatively incorrect results.

PMID- 11592695
TI  - Comparison of energy components of proteins from thermophilic and mesophilic
      organisms.
AB  - In order to infer the energetic determinants of thermophilic proteins, molecular
      mechanics calculations were applied to five proteins from thermophilic eubacteria
      and their mesophilic homologs. The energy function includes a hydration term as
      well as the electrostatic contribution from the solvent in addition to the usual
      conformational energy terms. We calculated energy values for three different
      states of each protein: the native, near-native, and unfolded structures. The
      energy difference and its components between pairs of these states were compared.
      The hypothetical near-native structures have almost the same backbone
      conformation as the native structure but with largely distorted side-chain
      packing, thus enabling us to extract the energy components important for
      stabilizing the native backbone topology itself, irrespective of structural
      details. It was found that the sum of the electrostatic and hydration energies,
      although of large positive values, were consistently lower for the thermophilic
      proteins than for their mesophilic counterparts. This trend was observed in the
      energy difference not only between the native and unfolded structures, but also
      between the near-native and unfolded structures. In contrast, the energy
      components regarding side-chain packing did not show any clear tendency. These
      results suggest that the thermophilic proteins are stabilized so that the precise
      packing of the native structure does not significantly affect the stability.
      Implications of this conclusion are also discussed.

PMID- 11592696
TI  - Mutations stabilizing an open conformation within the external region of the
      permeation pathway of the potassium channel KcsA.
AB  - Four subunits of the bacterial Streptomyces lividans protein KcsA form a K+
      channel which can be functionally reconstituted in vitro. Here we show that
      substitution of the tyrosine residue 82 by cysteine, valine or threonine, but not
      by glycine, led to functional channel types. Like the wild-type (WT) and an L81C
      channel, the mutant channels exhibit an internal pH-sensitive side and are cation
      selective. Based on the relative positions of the blocker tetraethylammonium
      within the electric field, the external entryways of the channels are concluded
      to have similar dimensions. For inward currents, the WT and the mutant channels
      vary in the occupancy of their subconductance states and concomitantly in their
      mean currents. Rectification properties are scarcely (L81C), little (Y82C) or
      considerably (Y82T and Y82V) altered. The data suggest that the amino acid type
      in position 82 stabilizes to varying degrees an open conformation within the
      external region of the permeation pathway.

PMID- 11592697
TI  - Experimental herpes-like viral infections in marine bivalves: demonstration of
      interspecies transmission.
AB  - Since 1972, herpes-like virus infections have been reported in several marine
      bivalve species around the world. Viral detection was often associated with high
      mortality rates in larvae and spat. To determine whether a single virus is able
      to infect different bivalve host species, we carried out experimental
      transmission assays. As a first step, 8 assays were performed to infect axenic
      Crassostrea gigas larvae with virus from infected C. gigas larvae using a
      previously described protocol. The protocol appeared reliable and PCR was
      confirmed as a powerful technique for detecting viral DNA in experimentally
      infected oysters. The defined protocol was then applied to infect different
      bivalve species. Interspecies viral transmission was demonstrated under
      laboratory conditions. The same phenomenon may occur in private hatcheries and
      may be promoted by intensive rearing conditions. This hypothesis is reinforced by
      reports of concomitant mortalities in the larvae of several bivalve species and
      by the first molecular analysis of infected larval samples.

PMID- 11592698
TI  - Streptococcus iniae inhibition of apoptosis of nonspecific cytotoxic cells: a
      mechanism of activation of innate immunity in teleosts.
AB  - Nonspecific cytotoxic cells (NCC) may provide innate anti-bacterial resistance
      against Streptococcus iniae infections in tilapia. The mechanism of immunity
      would be elaboration and release of various cytokines, augmentation of
      inflammation and amplification of increased antigen processing. To investigate
      bacterial regulation of NCC function, 2 different processes of cellular pathology
      were examined: apoptosis and necrosis. Different isolates of S. iniae from
      diseased teleosts, a dolphin and a human were tested. All isolates were examined
      for their ability to produce apoptosis and/or necrosis on freshly purified
      tilapia NCC and on a tilapia continuous cell line (i.e. TMB-8 cells). Two
      different isolates (9033 and 173) inhibited the outer membrane expression of
      phosphatidylserine (PS) by NCC, an early sign of apoptosis. This occurred at 4 h
      post-treatment and lasted throughout the 24 h treatment period. All other
      isolates either did not differ from control levels or produced a small increase
      in PS expression by NCC. The early reduction in PS expression occurred
      concomitantly with increased necrosis associated with nonspecific DNA
      fragmentation. Two-color flow cytometry (Annexin-V vs propidium iodide staining)
      demonstrated the specificity of Annexin-V binding. Experiments were also done to
      determine the effects of S. iniae on TMB-8 cells. Treated TMB-8 cells did not
      produce appreciable Annexin-V binding. Compared to the ATCC strain, 9033 produced
      high levels of necrosis-associated DNA fragmentation of TMB-8 cells at 4 and 8 h
      post-treatment. These data indicated that different isolates of S. iniae may
      regulate NCC anti-bacterial resistance by causing reduced levels of programmed
      cell death (PCD), increased necrosis and associated enhancement of inflammatory
      responses. Understanding the relevance of these bacterial effects on NCC may be
      an important consideration in the evaluation of isolates used in vaccine/
      bacterin production.

PMID- 11592699
TI  - Is Aeromonas hydrophila the dominant motile Aeromonas species that causes disease
      outbreaks in aquaculture production in the Zhejiang Province of China?
AB  - The significance of Aeromonas hydrophila in association with disease outbreaks in
      aquaculture production in the Zhejiang province of China was investigated.
      Bacteriological examination of moribund fish and crabs resulted in 95 bacterial
      isolates: 88 bacterial isolates from fish and 7 isolates from crabs. PCR and
      traditional biochemical methods were used for identification of A. hydrophila.
      Out of 69 motile aeromonads, 35 isolates were identified as A. hydrophila by
      biochemical tests. However, 6 of those were not identified as A. hydrophila by a
      species specific PCR method. Serotyping revealed 2 dominant serotypes (O9 and
      O97) among A. hydrophila isolates. The data presented show that approximately 42%
      of the motile aeromonads isolated from disease outbreaks among various fish
      species were A. hydrophila. It is noteworthy that A. hydrophila accounted for
      more than 50% of the isolated aeromonands isolated from crucian carp Carassius
      carassius and Wuchang bream Megalobrama amblycephala with haemorrhagic
      septicaemia. Although this species was the most frequently isolated organism from
      internal organs of diseased fish and crabs in the present study, other motile
      Aeromonas spp. were also found. The PCR assay was useful in preventing
      misidentification of A. hydrophila, which may occur when only phenotypic tests
      are employed.

PMID- 11592700
TI  - Evidence that infectious stages of Tetracapsula bryosalmonae for rainbow trout
      Oncorhynchus mykiss are present throughout the year.
AB  - Proliferative kidney disease (PKD) is a hyperplastic condition of the lymphoid
      tissue of salmonids infected with the spores of Tetracapsula bryosalmonae, a
      myxozoan parasite formerly designated PKX, which has recently been described as a
      parasite of several species of bryozoans. The occurrence of PKD is generally
      associated with seasonal increase in water temperature, with research indicating
      that transmission of the disease does not occur below 12 to 13 degrees C. This
      suggested that the infectious stages are absent from about November to
      March/April. Here we document the transmission of PKD at water temperatures and
      seasons previously considered to be non permissive for PKD infection. The
      exposure of naive rainbow trout Oncorhynchus mykiss (Walbaum) to PKD-infected
      water ranging from 8 to 13 degrees C during the Autumn, Winter and early Spring,
      resulted in the infection of kidney interstitium once the trout were transferred
      to 16 degrees C. In addition, cohabitation studies were conducted with the
      bryozoan host Fredericella sultana collected from a river at times of low
      seasonal temperatures because this bryozoan species overwinters as living
      colonies. Cohabitation of trout with colonies of F sultana in parasite-free city
      water at 16 degrees C, also led to renal lymphoid tissue infection with the
      parasite and even to nephromegaly. Our results provide evidence that the
      infectious stages of T bryosalmonae for rainbow trout were present in the water
      throughout the entire year and that the impact of temperature on the development
      of PKD is primarily a result of the kinetics of Tetracapsula multiplication in
      bryozoan and fish hosts.

PMID- 11592701
TI  - Relations between histopathology and parasitaemias in Oncorhynchus mykiss
      infected with Cryptobia salmositica, a pathogenic haemoflagellate.
AB  - One group (n = 50) of juvenile rainbow trout Oncorhynchus mykiss was inoculated
      intraperitoneally with 2000 (low dose [LD]) and another group (n = 50) with
      20,000 (high dose [HD]) Cryptobia salmositica fish(-1). The histopathology was a
      generalised inflammatory reaction, and lesions were in connective tissues and in
      the reticulo-endothelial system. In the LD group, the first lesions were observed
      in the liver, gills and spleen at 2 wk post infection (pi) while in the HD group
      they were in the liver and gills at 1 wk pi. Endovasculitis and mononuclear cell
      infiltration were observed at 3 wk pi in the HD group. These were followed by
      tissue necrosis and extravascular infiltration of parasites at 4 wk pi. The
      severity of lesions was directly related to parasitaemias in the blood and
      extravascular location of parasites. In the HD group, the most extensive tissue
      necrosis was at 4 wk pi and in the LD group it was 6 to 7 wk pi. Necrosis in the
      vital organs (liver, kidney and depletion of the haematopoeitic tissues) and
      anaemia were probably in part responsible for mortality of fish during acute
      disease. Regeneration and replacement of necrotic tissues were seen at 7 to 9 wk
      pi in the HD group, and it was most noticeable in haematopoietic and reticular
      tissues. These occurred during the recovery phase of the disease and were
      associated with significant reduction in blood parasitaemia.

PMID- 11592702
TI  - Philasterides dicentrarchi (Ciliophora, Scuticociliatida) as the causative agent
      of scuticociliatosis in farmed turbot Scophthalmus maximus in Galicia (NW Spain).
AB  - Two outbreaks of scuticociliatosis affecting farmed turbot Scophthalmus maximus
      in Galicia are described. Moribund fish showed cutaneous ulcers, darkened skin,
      swimming behaviour alterations, exophthalmos, and/or abdominal distension as a
      result of accumulation of ascitic fluid in the body cavity. Ciliates were
      detected in fresh mounts of practically all organs and tissues, including the
      blood and ascitic fluid. Histopathological studies revealed severe encephalitis
      and meningitis (associated with different degrees of softening or liquefaction of
      the brain), necrosis of the hepatic parenchyme, severe oedema of the intestinal
      wall, degeneration of muscle fibres, hyperplasia of the branchial epithelium,
      and/or vascular and perivascular inflammation. In some cases, parasites are
      surrounded by abundant monocytic and lymphocytic infiltrate. We report the
      morphological and biometric characteristics of this ciliate, which allow
      identification as Philasterides dicentrarchi. We discuss possible routes of entry
      into the host, and environmental factors possibly facilitating infection.

PMID- 11592703
TI  - Parasitism by the protozoan Perkinsus atlanticus favours the development of
      opportunistic infections.
AB  - It has been suggested that opportunistic pathogens could contribute to the
      mortality of Perkinsus atlanticus-infected clams. Examination of Tapes
      semidecussatus clams from the northern Mediterranean coast of Spain revealed that
      while 86% of the clams heavily infected with P. atlanticus were co-infected by
      bacteria and/or viruses, neither non-infected nor lightly P. atlanticus-infected
      specimens had bacterial or viral infections. The bacteria, which had a Gram
      negative cell wall, were always located in the apical pole of gill epithelial
      cells and enclosed within membranous compartments. Bacteria-containing cells were
      hypertrophied and showed dysplasia with loss of cilia and microvilli. The viruses
      shared ultrastructural, morphologic and cytopathic characteristics of a
      polyomavirus. Viral particles with icosahedral symmetry were found in both the
      cytoplasm and the nucleus of numerous cell types. Virus-infected cells showed
      severe alterations, including hypertrophy, reduction of the intracellular
      compartments and extrusion of the nuclear envelope. Moreover, gill epithelial
      cells showed disorganization and swelling of the apical region, which affected
      the ciliary structure. Our findings show that P. atlanticus parasitism favours
      the development of opportunistic infections which have detrimental effects in
      this clam population.

PMID- 11592704
TI  - Actinosporean infections in oligochaetes in a river system in southwest Ireland
      with descriptions of three new forms.
AB  - Sediment samples were collected in April, June and August 1998 from a river in
      southwest Ireland. A total of 1,836 oligochaete specimens were collected from
      these sediments, and examined for actinosporean infections. Actinosporean
      infected oligochaetes have been determined, symptoms and course of infection have
      been considered and the spores released from them have been described. Spore
      characteristics for each actinosporean were defined and the prevalence of
      infection in each oligochaete species was also determined. The overall prevalence
      of infection with actinosporeans within the oligochaete sample was approximately
      2%. Seven types were distinguished, belonging to echinactinomyxon,
      aurantiactinomyxon and neoactinomyxum forms, from Tubifex ignotus, Lumbriculus
      variegatus and Limnodrilus hoffmeisteri, and compared with actinosporean types
      previously reported in the literature. Three of these forms have not been
      previously described, while the other 4 are morphologically and morphometrically
      similar to known forms. These actinosporeans may be stages in myxozoan life
      cycles.

PMID- 11592705
TI  - Infectious hematopoietic necrosis virus antibody profiles in naturally and
      experimentally infected Atlantic salmon Salmo salar.
AB  - Atlantic salmon Salmo salar naturally and experimentally exposed to infectious
      hematopoietic necrosis virus (IHNV) in British Columbia, Canada, developed
      antibodies against the virus. More than 50% of the fish exposed to IHNV remained
      seropositive for several months after the IHN epizootic had subsided. The virus
      itself could not be detected in asymptomatic fish once the fish had recovered
      from IHN. The persistence of IHNV-specific antibodies in a large percentage of
      Atlantic salmon, from 4 different populations that survived an outbreak of IHN,
      and the lack of IHNV-specific antibodies in fish with no history of the disease,
      suggests that serology may be a useful tool for determining previous exposure to
      the virus. It may be important to determine whether Atlantic salmon have been
      infected with IHNV because, although the virus is difficult to detect in
      asymptomatic fish, an incidental finding suggests it may persist in a small
      number of fish after the outbreak has subsided. Furthermore, the presence of
      seropositive fish would be an indication that the virus may be enzootic at a
      farm, and such information would thus aid producers with stocking decisions.

PMID- 11592706
TI  - First published record of the pathogenic monogenean parasite Neobenedenia melleni
      (Capsalidae) from Australia.
AB  - The monogenean Neobenedenia melleni (MacCallum, 1927) Yamaguti 1963 is a well
      known and virulent pathogen in culture conditions recorded from the skin of many
      teleost fish species worldwide. Until now, N. melleni has not been reported from
      wild or cultured fish in Australian waters. This study documents a recent
      outbreak of N. melleni that occurred on Lates calcarifer (barramundi) cultivated
      in sea cages in Hinchinbrook Channel between Hinchinbrook Island and mainland
      Queensland, Australia, which resulted in the loss of 200,000 fish (50 tonnes).
      The origin of this outbreak is unclear because N. melleni has not been recorded
      from any wild host species in Australia and strict quarantine regulations exclude
      the possibility of its introduction on imported fish. We propose that N. melleni
      occurs naturally on wild populations of some teleost species in Australian waters
      and that the few surveys of wild fish conducted along the east coast have failed
      to report this species. The possibility that uncharacteristically low water
      temperatures led to the outbreak is discussed.

PMID- 11592707
TI  - Transgenics, uncertainty and public credibility.

PMID- 11592708
TI  - Over-expression of the murine pIgR gene in the mammary gland of transgenic mice
      influences the milk composition and reduces its nutritional value.
AB  - The polymeric immunoglobulin receptor (pIgR) transports dimeric IgA (dIgA) across
      epithelial cells lining mucosal and glandular tissues, including the mammary
      gland. Four transgenic mouse lines were generated, overexpressing the murine pIgR
      gene in the epithelial cells of their mammary glands under control of the
      regulatory sequences of the bovine alphas1-casein gene. Ten to 270-fold over
      expression of the IgA receptor was achieved. The pIgR transgenic line 3644,
      having the highest pIgR transgene expression, had a markedly altered milk
      composition compared to non-transgenic mice. In the other three transgenic lines
      the milk composition, other than SC levels, were not changed. In the milk of line
      3644 a protein of 31 kD was lacking and a new protein of 11 kD appeared at
      relatively high levels. The 31 kD protein was identified as k-casein and the 11
      kD protein as serum amyloid A-1 (SAA1). The nutritional value of the milk of
      females from transgenic line 3644 was dramatically impaired as shown by the
      retarded growth and development of the pups, leading to death two weeks after
      birth.

PMID- 11592709
TI  - Rapid screening for dominant negative mutations in the beet necrotic yellow vein
      virus triple gene block proteins P13 and P15 using a viral replicon.
AB  - Point mutations were introduced into the genes encoding the triple gene bock
      movement proteins P13 and P15 of beet necrotic yellow vein virus (BNYVV).
      Mutations which disabled viral cell-to-cell movement in Chenopodium quinoa were
      then tested for their ability to act as dominant negative inhibiters of movement
      of wild-type BNYVV when expressed from a co-inoculated BNYVV RNA 3-based
      replicon. For P13, three types of mutation inhibited the movement function: non
      synomynous mutations in the N- and C-terminal hydrophobic domains, a mutation at
      the boundary between the N-terminal hydrophobic domain and the central
      hydrophilic domain (mutant P13-A12), and mutations in the conserved sequence
      motif in the central hydrophilic domain. However, only the 'boundary' mutant P13
      A12 strongly inhibited movement of wild-type virus when expressed from the co
      inoculated replicon. Similar experiments with P15 detected four movement
      defective mutants which strongly inhibited cell-to-cell movement of wild-type
      BNYVV when the mutants were expressed from a co-inoculated replicon. Beta
      vulgaris transformed with two of these P15 mutants were highly resistant to
      fungus-mediated infection with BNYVV.

PMID- 11592710
TI  - Uniform GFP-expression in transgenic medaka (Oryzias latipes) at the F0
      generation.
AB  - A green fluorescent protein (GFP) cDNA flanked by inverted terminal repeats (ITR)
      of adeno-associated virus was constructed. The construct sharply improved the
      efficiency and specificity of the transient expression of genes driven by two
      general promoters (cytomegalovirus and medaka beta-actin) and one muscle-specific
      promoter (zebrafish alpha-actin) in transgenic medaka. In addition, treatment
      with ITR sequence-containing constructs resulted in a dramatic increase in the
      number of embryos showing uniform GFP-expression at F0. Of the GFP-positive
      embryos, 34.6% (81/234), 10% (10/60), and 18% (38/212) showed homogenous GFP
      expression for the derivative constructs of the cytomegalovirus, alpha-actin, and
      beta-actin promoters, respectively. As a result of uniform GFP-expression, green
      fluorescence in founders was (a) extended for an entire lifetime without
      degradation, and (b) transmitted as a genetic trait to F1 and F2 progeny of some
      transgenic lines via Mendelian inheritance. A Southern blot analysis revealed a
      random integration of the transgene into the genome of founders and progeny in
      both head-to-tail and tail-to-tail concatemerization patterns. Interestingly,
      some transgenic medaka with uniform and strong fluorescence could be visually
      noticeable to the unaided eye.

PMID- 11592711
TI  - FLP/FRT-mediated restoration of normal phenotypes and clonal sectors formation in
      rolC transgenic tobacco.
AB  - Site-specific recombination systems have been shown to excise transgene DNA
      sequences positioned between their cognate target sites, and thus be used to
      generate clonal sectors in transgenic plants. Here we characterized clonal
      sectors derived from genetic reversion of rolC (A. rhizogenes)--induced
      vegetative and reproductive phenotypes, mediated by FLP recombinase from S.
      cerevisiae, in tobacco. The constitutive expression of rolC induces pleiotropic
      effects including reduced apical dominance and plant height, lanceolate and pale
      green leaves and small, male-sterile flowers. Two transgenic male-sterile tobacco
      lines (N. tabacum, Samsun NN) expressing a 35sP-rolC gene construct flanked by
      two FRT (FLP recombinase target) sites, were cross-pollinated with pollen from a
      constitutive 35sP-FLP expressing line. Three main phenotypes were generated in
      result of recombinase-mediated excision of the 35sP-rolC locus in the F1 (FLP x
      FRT-35sP-rolC-FRT) hybrid progenies: (a) restoration of male fertility,
      associated with reversion to normal leaf phenotypes prior to flower bud
      formation, (b) development of normal and fertile lateral shoot sectors on the
      background of rolC-type plants, (c) restoration of partially fertile flowers,
      associated with display of peripheral normal leaf sectors surrounding rolC-type
      inner-leaf tissues, consistent with periclinal chimeras. These results, supported
      by DNA molecular analysis, indicate that site-specific recombination might be
      used as a relatively efficient tool for generation of transgenic periclinal
      chimeric plants.

PMID- 11592713
TI  - Expression and characterization of monocot rice cytosolic CuZnSOD protein in
      dicot Arabidopsis.
AB  - Cytosolic CuZnSOD removes deleterious superoxides from plant cells. In order to
      understand its function better, we sought to express a monocot CuZnSOD gene in
      transgenic Arabidopsis. We constructed a transgene using the CaMV 35S promoter to
      express a rice cytosolic CuZnSOD gene in Arabidopsis and generated over 200
      transformants. A 16 kD polypeptide, the same size as the native rice CuZnSOD
      polypeptide, was detected in the transgenic Arabidopsis. Interestingly, two forms
      of rice CuZnSOD, rSODI and rSODII, having the same dimeric size, were detected in
      the transgenic plants. rSODII protein was relatively abundant but had low
      specific activity. In contrast, rSODI protein was relatively rare and had high
      specific activity. Inter-conversion of rSODI and rSODII could be achieved by the
      addition and removal of copper ions into the purified recombinant SOD and to the
      leaf extract of transgenic plants. Our analysis indicates that rSODI most likely
      corresponds to native rice CuZnSOD that has incorporated the Cu and Zn ions
      required for full activity, whereas the less active rSODII form may not have
      properly incorporated the necessary copper ions.

PMID- 11592712
TI  - Expression of the human insulin gene in the gastric G cells of transgenic mice.
AB  - The goal of this study was to engineer gastrin-producing G cells of the gastric
      antrum to produce insulin. A pGas-Ins chimeric gene in which the gastrin promoter
      drives expression of the human insulin gene was constructed and was validated by
      transient transfection of GH4 and AGS cells. RT-PCR analysis and sequencing
      revealed three forms of differentially spliced insulin mRNA in GH4 cells
      transiently transfected by pGas-Ins. Gas-Ins transgenic mice were generated
      utilizing this chimeric gene. Northern blot analysis, in situ hybridization, and
      immunohistochemistry demonstrated expression of the human insulin gene
      specifically in antral G cells. Northern blot analysis demonstrated that the
      shortest of the insulin mRNA three forms is predominantly expressed in stomach
      tissue. RT-PCR analysis also showed expression of the transgene in colon,
      pancreas, and brain tissues that was undetectable by northern analysis. We
      conclude that gastrin promoter can be used for targeting expression of human
      insulin to antral G cells and that antral G cells can express human insulin.
      Further refining of the chimeric gene design is required to enhance expression.

PMID- 11592714
TI  - Dramatically accelerated growth and extraordinary gigantism of transgenic mud
      loach Misgurnus mizolepis.
AB  - Transgenic mud loaches (Misgurnus mizolepis), in which the entire transgene
      originated from the same species, have been generated by microinjecting the mud
      loach growth hormone (mlGH) gene fused to the mud loach beta-actin promoter. Out
      of 4,100 eggs injected, 7.5% fish derived from the injected eggs showed
      dramatically accelerated growth, with a maximum of 35-fold faster growth than
      their non-transgenic siblings. Many fast-growing transgenic individuals showed
      extraordinary gigantism: their body weight and total length (largest fish
      attained to 413 g and 41.5 cm) were larger and longer than even those of 12-year
      old normal broodstock (maximum size reached to 89 g and 28 cm). Of 46 transgenic
      founders tested, 30 individuals transmitted the transgene to next generation with
      a wide range of germ-line transmission frequencies ranging from 2% to 33%. The
      growth performance of the subsequent generation (F1) was also dramatically
      accelerated up to 35-fold, although the levels of enhanced growth were variable
      among transgenic lines. Three transgenic germ-lines up to F4 were established,
      showing the expected Mendelian inheritance of the transgene. Expression of GH
      mRNA in many tissues was detected by RT-PCR analyses. The time required to attain
      marketable size (10 g) in these transgenic lines was only 30-50 days after
      fertilization, while at least 6 months in non-transgenic fish. Besides growth
      enhancement, significantly improved feed-conversion efficiency up to 1.9-fold was
      also observed.

PMID- 11592716
TI  - My affair with TR.

PMID- 11592715
TI  - Transgenic radish (Raphanus sativus L. longipinnatus Bailey) by floral-dip method
      -plant development and surfactant are important in optimizing transformation
      efficiency.
AB  - Transgenic radish (Raphanus sativus L. longipinnatus Bailey) plants were produced
      from the progeny of plants which were dipped into a suspension of Agrobacterium
      carrying both the beta-glucuronidase (gusA) gene and a gene for resistance to the
      herbicide Basta (bar) between T-DNA border sequences. The importance of
      development of the floral-dipped plant and presence of surfactant in the
      inoculation medium were evaluated in terms of transgenic plant production. Plants
      dipped at the primary bolt stage of growth, into a suspension of Agrobacterium
      containing 0.05% (v/v) Silwet L-77 resulted in optimum transformation efficiency,
      with 1.4% from 1110 seeds. The presence of Pluronic F-68 or Tween 20 in the
      inoculation medium was beneficial towards transgenic plant output compared to
      treatments without surfactant. Putative transformed T1 plants were efficiently
      selected by spraying with 0.03% (v/v) Basta and all herbicide-resistant plants
      tested positive for GUS activity when analysed both histochemically and
      fluorometrically. Southern analysis revealed that both the gusA and bar genes
      integrated into the genome of transformed plants and segregated as dominant
      Mendelian traits. These results demonstrate that radish can be genetically
      modified for the improvement of this important vegetable crop.

PMID- 11592717
TI  - Modulation of protein synthesis in rabbit inner cell mass-derived cells by FGF-2.
AB  - Gastrulation is a critical step in vertebrate development, that depends on
      synergistic effects of several signalling molecules, including fibroblast growth
      factor-2 (FGF-2). To follow this phenomenon in vitro we isolated rabbit inner
      cell masses (ICMs) at embryonic day 4 and we exposed ICM-derived cells to FGF-2.
      Then, we analysed the quantitative differences in rates of protein synthesis from
      day 3 to day 5 of culture by two-dimensional (2D) gel electrophoresis. Here we
      show that both up- and down-regulation of protein synthesis took place in ICM
      derived cells upon their exposure to FGF-2. The effect of FGF-2 was most
      pronounced at day 4 of culture, when the changes were very much in favour of a
      set of down-regulated proteins. To test the significance of this period of time
      for FGF-2-mediated regulation of protein synthesis, cells were grown without FGF
      2 and then they were pulse-treated with FGF-2 at the end of day 4. When compared
      to the continuous culture with FGF-2, the FGF-2 pulse resulted in a quite
      indistinguishable pattern of up- and down-regulated proteins. Thus, the readiness
      of ICM-derived cells to accept and respond to the FGF-2 signals may be of limited
      duration.

PMID- 11592718
TI  - Increase of plasma eCG binding rate after administration of repeated high dose of
      eCG to cows.
AB  - Equine chorionic gonadotrophin (eCG) is still used to promote follicular growth
      in cattle and, more recently with an increased frequency of administration, in
      ovum pick-up protocols. The aim of this experiment was to verify the possible
      effect of high frequency of administration on the immune response to eCG. The
      profiles of eCG binding rate, in the blood of two groups (A, B) of 4 primiparous
      cross breed beef cows (3-3.5 years old) submitted weekly for 5 to 10 weeks to
      repeated high doses (1000-2000 IU) of equine chorionic gonadotrophin, are
      presented in this paper. A sensitive radiometric method was used to detect
      antibodies in plasma. The profiles clearly indicated a marked increase of eCG
      binding rate after 3 to 5 injections of the exogenous hormone to the females. The
      statistical analysis of the results established that treatments induced a
      significant increase (P < 0.01) in binding rates after 6 and 3 injections in
      group A and B respectively. These binding rates remained elevated for at least 1
      week following the last injection and decreased afterwards. The values of plasma
      binding rates following repeated eCG administration differed significantly
      between groups (0.90+/-1.04 and 1.04+/-0.11 for groups A and B before treatment
      versus 11.77+/-0.92, 6.70+/-0.85 for groups A and B after treatment, P < 0.01)
      and from one cow to another (P < 0.01) with some cows presenting no significant
      immune response while others were more reactive against the hormone (at least 3
      injections).

PMID- 11592719
TI  - Sperm quality and reproductive traits in male offspring of female rabbits exposed
      to lindane (gamma-HCH) during pregnancy and lactation.
AB  - Fifteen Grimaud female hybrid rabbits, 135 days old and weighting an average of
      3.74+/-0.01 kg each, were administered an oral dose of 1 mg x kg(-1) body weight
      of Lindane during gestation and lactation period. Fertility rate, libido, volume
      of ejaculate, concentration and morphology of spermatozoa were investigated to
      test the effects of the treatment on reproductive traits of first generation male
      rabbits. Ultrastructure of abnormal spermatozoa was described by Transmission
      Electron Microscopy and the different abnormalities were quantified. The results
      obtained indicate that low dose exposure of Lindane has effects on spermatozoa
      ultrastructure that proved to be susceptible to the treatment with the pesticide
      (cytoplasmic droplets: 5.3% in control group and 10.3% in Lindane group, P < or =
      0.05; coiled tails: 1.3% in control group and 4.3% in Lindane group, P < or =
      0.05) and could be utilised as a good marker of toxicity.

PMID- 11592720
TI  - The effects of alpha-lactalbumin and whey protein concentrate on alpha-amino
      acids, calcium and phosphorus levels in blood and gastrointestinal tract of rats.
AB  - The effects of two dietary proteins on alpha-amino acids, calcium and phosphorus
      concentrations in plasma, stomach and intestine were investigated in rats trained
      to consume, in a single two-hour daily meal, diets containing a-lactalbumin
      (alpha-la) or whey protein concentrate (WPC) for two weeks. The results indicated
      that the concentrations of calcium and phosphorus in the gastrointestinal tract
      and that of a-amino acids in portal vein were not significantly influenced by the
      nature of diets. The amount of alpha-amino acids in the gastrointestinal tract of
      rats fed on WPC diet was significantly (p < 0.001) higher than that of alpha-la
      group. The levels of insoluble calcium and insoluble phosphorus in the small
      intestine were significantly (p < 0.001) higher in alpha-la group than in WPC
      group. These results indicated that the kinetics of alpha-amino acids, calcium
      and phosphorus were differently influenced by the nature of diet ingested, the
      sampling time and the sites of sample collections.

PMID- 11592721
TI  - Sheep embryos derived from FSH/eCG treatment have a lower in vitro viability
      after vitrification than those derived from FSH treatment.
AB  - In the non breeding period, the effect of two superovulatory treatments (eCG/FSH
      in single dose or FSH alone in four decreasing doses) on the production of embryo
      quality following in vitro viability after vitrification procedures was
      investigated using forty-four adult Sarda breed ewes. In sheep treated with
      eCG/FSH, the mean number of corpora lutea was significantly (P < 0.05) higher
      (11.8+/-4.0 vs. 8.05+/-3.8), although the recovery rate was significantly (P <
      0.01) lower (74.6 vs. 59.9) than with FSH alone. After vitrification (ethylene
      glycol and glycerol) was repeated three times, the rates of re-expansion at first
      and second warming were significantly (P < 0.01) higher in embryos derived from
      FSH alone than in those with both gonadotrophins (94.9 and 41.9 vs. 72.8 and
      18.6) and after the last vitrification the hatched blastocyst rates were 22.5 and
      7.6. After differential stain, blastocysts derived from FSH alone showed a mean
      number of cells significantly higher than blastocysts from eCG/FSH (184.2 vs.
      157.7). It was concluded that superovulatory treatment with eCG/FSH may increase
      the ovarian responses compared with FSH alone, but these embryos showed a
      reduction in viability rates after repeated vitrification.

PMID- 11592722
TI  - Reproductive performance of multiparous rabbit lactating does: effect of lighting
      programs and PMSG use.
AB  - This study aims to determine if Pregnant Mare Serum Gonadotrophin (PMSG), used
      for oestrous synchronization in multiparous lactating does, could be replaced by
      one of the following lighting schedules without impairing reproductive
      performance: (a) 12-h L (light)/12-h D (dark) or (b) 8-h L/16-h D, until day 6
      before artificial insemination (AI), when in both cases photoperiod was changed
      to 16-h L/8-h D and maintained until the day of AI, and in the following 4 days
      post Al the light hours were progressively reduced to the initial schedules. Two
      groups of 20 does each were respectively submitted to one of the lighting
      schedules specified above. All does were artificially inseminated in 6
      consecutive cycles at 42 days intervals. In the first, third and fifth AIs, PMSG
      (20 IU/doe via sc 48 h before AI) was used in the two groups of does, whereas in
      the second, fourth and sixth Als no hormonal treatment was used. Degree of
      oestrous synchronization (also referred in text as sexual receptivity) was
      estimated by the colour of the vulva at AI. Reproductive performance of does was
      evaluated based on fertility (kindling rates), prolificity, mortality at birth,
      mortality at 21 days post birth, weight of the litter at 21 days post birth and
      number of weaned rabbits. Oestrous was better synchronized when PMSG was used
      with any of the two lighting programs. Without using PMSG, a photoperiod of 12-h
      L/12-h D until 6 days before AI resulted in a better sexual receptivity of does
      than 8-h L/16-h D. Fertility, prolificity, mortality of young rabbits at 21 days,
      the weight of the litters at 21 days and the number of weaned rabbits did not
      vary with the lighting program and were not affected by the PMSG treatment.
      Mortality at birth, however, was higher (+1 dead kit per litter) in litters
      housed under a light program of 12-h L/12-h D. Global productivity (number of
      weaned rabbits per 100 inseminated does) was better when using PMSG, for both
      lighting schedules. When using a photoperiod of 12-h L/12-h D until 6 days before
      AI, and omitting the PMSG treatment, global productivity was scarcely reduced,
      however, it was considerably impaired when using a photoperiod of 8-h L/16-h D
      until 6 days before AI and no PMSG treatment.

PMID- 11592723
TI  - Utilisation of phytate phosphorus by rumen bacteria in a semi-continuous culture
      system (Rusitec) in lactating goats fed on different forage to concentrate
      ratios.
AB  - Experimental data on phytate phosphorus utilisation by ruminants are scarce. The
      aim of this study was to estimate the phytase activity of rumen micro-organisms
      when phytate phosphorus supply is high. A semi-continuous culture system
      fermentor (RUSITEC) was used. The inoculum was obtained from eight goats fed on
      either high or low forage level diets. Experimental buffers only differed by the
      nature of phosphorus monosodium phosphate vs. corn sodium phytate. The nylon bags
      containing 15 g DM of substrate were removed after a 48-hour incubation period.
      The system was maintained for 15 days: 5 days for adaptation, in order to obtain
      a steady state, and 10 days for sampling and recording. No significant
      differences were observed for DM digestibility, gas production, pH, N-NH3, and
      SCFA for the different treatments. Bacterial efficiency of phytate phosphorus
      utilisation was significantly higher (p < 0.001) with organic P, but remained
      lower than the data usually reported in the literature. These results may be
      explained by the relative saturation of bacterial phytase activity when the
      buffer contains a high level of phytate phosphorus.

PMID- 11592724
TI  - Birth of piglets after OPS vitrification and transfer of compacted morula stage
      embryos with intact zona pellucida.
AB  - In swine, five to six days post-insemination, morulae and blastocysts are
      collected together after uterine flushing. The purpose of this study was to
      vitrify zona pellucida-intact morulae with Open Pulled Straw (OPS) technology and
      obtain piglets after transfer. Morulae (200) were vitrified after a two-step
      equilibration in ethylene glycol, dimethyl sulfoxide and sucrose in Hepes
      buffered TCM199 + 20% NBCS medium (TCM). 2-6 morulae were loaded into OPS and
      plunged into liquid nitrogen. At embryo warming, a three-step dilution with
      decreasing concentrations of sucrose was applied. In each of 10 recipients, 20
      morulae were transferred surgically. Day 25, gestation rate and the farrowing
      rate were 80% and 70%, respectively. The pregnant recipients farrowed from 1 to 8
      piglets and the survival of total transferred embryos was 13%. Although survival
      rates are still compromised, OPS technology is therefore appropriate to
      cryopreserve porcine morulae with intact zona pellucida.

PMID- 11592725
TI  - Genomic and functional characterization of polyunsaturated fatty acid
      biosynthesis in Caenorhabditis elegans.
AB  - The biosynthetic pathway for polyunsaturated fatty acids in the model animal
      Caenorhabditis elegans was examined in the context of the completed genome
      sequence. The genomic organization and location of seven desaturase genes and one
      elongase activity, all previously identified by functional characterization, were
      elucidated. A pathway for the biosynthesis of polyunsaturated fatty acids in C.
      elegans was proposed based on these genes. The role of gene duplication in enzyme
      evolution and proliferation is discussed.

PMID- 11592726
TI  - Conjugated linoleic acid supplementation in humans: effects on fatty acid and
      glycerol kinetics.
AB  - Recent studies with mouse adipocytes have shown that dietary conjugated linoleic
      acid (CLA) may reduce body fat by increasing lipolysis. The present study
      examined the effect of CLA supplementation on fatty acid and glycerol kinetics in
      six healthy, adult women who were participating in a controlled metabolic ward
      study. These women were fed six CLA capsules per day (3.9 g/d) for 64 d following
      a baseline period of 30 d. The subjects were confined to a metabolic suite for
      the entire 94-d study, where diet and activity were controlled and held constant.
      The rate of appearance (Ra) of glycerol, which indicates lipolytic rates, was
      similar at baseline and after 4 wk of CLA supplementation at rest (1.87 +/- 0.21
      and 2.00 +/- 0.39 micromol/kg/min, respectively) and during exercise (7.12 +/-
      0.74 and 6.40 +/- 0.99 micromol/kg/min, respectively). Likewise, the Ra of free
      fatty acids (FFA) was not significantly different after 4 wk of dietary CLA at
      rest (2.72 +/- 0.06 and 2.74 +/- 0.12 micromol/kg/min, respectively) or during
      exercise (6.99 +/- 0.40 and 5.88 +/- 0.29 micromol/kg/min, respectively). CLA
      supplementation also had no effect on the percentage of FFA released from
      lipolysis that were re-esterified. The apparent rate of FFA re-esterification was
      65.2 +/- 4.2% at rest and 32.1 +/- 3.44% during exercise. Four weeks of CLA
      supplementation had no significant effect on fatty acid or glycerol metabolism in
      healthy, weight-stable, adult women.

PMID- 11592727
TI  - Conjugated linoleic acid supplementation in humans--metabolic effects.
AB  - Supplementation with conjugated linoleic acid (CLA) induces a number of
      physiological effects in experimental animals, including reduced body fat
      content, decreased aortic lipid deposition, and improved serum lipid profile.
      Controlled trials on the effects of CLA in humans have hitherto been scarce. The
      aim of this study was to evaluate the effects of supplementation with CLA in
      healthy humans on anthropometric and metabolic variables and on the fatty acid
      composition of serum lipids and thrombocytes. Fifty-three healthy men and women,
      aged 23-63 yr, were randomly assigned to supplementation with CLA (4.2 g/d) or
      the same amount of olive oil during 12 wk in a double-blind fashion. The
      proportion of body fat decreased (-3.8%, P< 0.001) in the CLA-treated group, with
      a significant difference from the control group (P = 0.050). Body weight, body
      mass index, and sagittal abdominal diameter were unchanged. There were no major
      differences between the groups in serum lipoproteins, nonesterified fatty acids,
      plasma insulin, blood glucose, or plasminogen activator inhibitor 1 (PAI-1). In
      the CLA group the proportions of stearic, docosatetraenoic, and docosapentaenoic
      acids increased in serum lipids and thrombocytes, while proportions of palmitic,
      oleic, and dihomo-gamma-linolenic acids decreased, causing a decrease of the
      estimated delta-6 and delta-9 and an increase in the delta-5 desaturase
      activities. These results suggest that supplementation with CLA may reduce the
      proportion of body fat in humans and that CLA affects fatty acid metabolism. No
      effects on body weight, serum lipids, glucose metabolism, or PAI-1 were seen.

PMID- 11592728
TI  - Serum cholesterol predictive equations with special emphasis on trans and
      saturated fatty acids. an analysis from designed controlled studies.
AB  - The effects of dietary trans fatty acids on serum total and low density
      lipoprotein (LDL) cholesterol have been evaluated by incorporating trans fatty
      acids into predictive equations and comparing their effects with the effects of
      the individual saturated fatty acids 12:0, 14:0, and 16:0. Trans fatty acids from
      partially hydrogenated soybean oil (TRANS V) and fish oil (TRANS F) were included
      in previously published equations by constrained regression analysis, allowing
      slight adjustments of existing coefficients. Prior knowledge about the signs and
      ordering of the regression coefficients was explicitly incorporated into the
      regression modeling by adding lower and upper bounds to the coefficients. The
      amounts of oleic acid (18:1) and polyunsaturated fatty acids (18:2, 18:3) were
      not sufficiently varied in the studies, and the respective regression
      coefficients were therefore set equal to those found by Yu et al. [Yu, S., Derr,
      J., Etherton, T.D., and Kris-Etherton, P.M. (1995) Plasma Cholesterol-Predictive
      Equations Demonstrate That Stearic Acid Is Neutral and Monounsaturated Fatty
      Acids Are Hypocholesterolemic, Am. J. Clin. Nutr. 61, 1129-1139]. Stearic acid
      (18:0), considered to be neutral, was not included in the equations. The
      regression analyses were based on results from four controlled dietary studies
      with a total of 95 participants and including 10 diets differing in fatty acid
      composition and with 30-38% of energy (E%) as fat. The analyses resulted in the
      following equations, where the change in cholesterol is expressed in mmol/L and
      the change in intake of fatty acids is expressed in E%: delta Total cholesterol =
      0.01 delta(12:0) + 0.12 delta(14:0) + 0.057 delta(16:0) + 0.039 delta(TRANS F) +
      0.031 delta(TRANS V) - 0.0044 delta(18:1) - 0.017 delta(18:2, 18:3) and deltaLDL
      cholesterol = 0.01 delta(12:0) + 0.071 delta(14:0) + 0.047 delta(16:0) + 0.043
      delta(TRANS F) + 0.025 delta(TRANS V) - 0.0044 delta(18:1) - 0.017 delta(18:2,
      18:3). The regression analyses confirm previous findings that 14:0 is the most
      hypercholesterolemic fatty acid and indicate that trans fatty acids are less
      hypercholesterolemic than the saturated fatty acids 14:0 and 16:0. TRANS F may be
      slightly more hypercholesterolemic than TRANS V or there may be other
      hypercholesterolemic fatty acids in partially hydrogenated fish oil than those
      included in the equations. The test set used for validation consisted of 22 data
      points from seven recently published dietary studies. The equation for total
      cholesterol showed good prediction ability with a correlation coefficient of
      0.981 between observed and predicted values. The equation has been used by the
      Norwegian food industry in reformulating margarines into more healthful products
      with reduced content of cholesterol-raising fatty acids.

PMID- 11592729
TI  - Comparative bioavailability of dietary alpha-linolenic and docosahexaenoic acids
      in the growing rat.
AB  - Animal and human studies have indicated that developing mammals fed only alpha
      linolenic acid (18:3n-3) have lower docosahexaenoic acid (22:6n-3) content in
      brain and tissue phospholipids when compared with mammals fed 18:3n-3 plus 22:6n
      3. The aim of this study was to test the hypothesis that low bioavailability of
      dietary 18:3n-3 to be converted to 22:6n-3 could partly explain this difference
      in fatty acid accretion. For that purpose, we determined the partitioning of
      dietary 18:3n-3 and 22:6n-3 between total n-3 fatty acid body accumulation,
      excretion, and disappearance (difference between the intake and the sum of total
      n-3 fatty acids accumulated and excreted). This was assessed using the
      quantitative method of whole-body fatty acid balance in growing rats fed the same
      amount of a 5% fat diet supplying either 18:3n-3 or 22:6n-3 at a level of 0.45%
      of dietary energy (i.e., 200 mg/100 g diet). We found that 58.9% of the total
      amount of 18:3n-3 ingested disappeared, 0.4% was excreted in feces, 21.2%
      accumulated as 18:3n-3 (50% in total fats and 46% in the carcass-skin
      compartment), and 17.2% accumulated as long-chain derivatives (14% as 22:6n-3 and
      3.2% as 20:5n-3 + 22:5n-3). Similar results were obtained from the
      docosahexaenoate balance (as % of the total amount ingested): disappearance,
      64.5%; excretion, 0.5%; total accumulation, 35% with 30.1% as 22:6n-3. Thus, rats
      fed docosahexaenoate accumulated a twofold higher amount of 22:6n-3, which was
      mainly deposited in the carcass-skin compartment (68%). Similar proportions of
      disappearance of dietary 18:3n-3 and 22:6n-3 lead us to speculate that these two
      n-3 polyunsaturated fatty acids were beta-oxidized in the same amount.

PMID- 11592730
TI  - Hyperthyroidism affects lipid metabolism in lactating and suckling rats.
AB  - Two per thousand pregnant women have hyperthyroidism (HT), and although the
      symptoms are attenuated during pregnancy, they rebound after delivery, affecting
      infant development. To examine the effects of hyperthyroidism on lactation, we
      studied lipid metabolism in maternal mammary glands and livers of hyperthyroid
      rats and their pups. Thyroxine (10 microg/100 g body weight/d) or vehicle-treated
      rats were made pregnant 2 wk after commencement of treatment and sacrificed on
      days 7, 14, and 21 of lactation with the litters. Circulating triiodothyronine
      and tetraiodothyronine concentrations in the HT mothers were increased on all
      days. Hepatic esterified cholesterol (EC) and free cholesterol (FC) and
      triglyceride (TG) concentrations were diminished on days 14 and 21. Lipid
      synthesis, measured by incorporation of [3H]H2O into EC, FC, and TG, fatty acid
      synthase, and acetyl CoA carboxylase activities increased at day 14, while
      incorporation into FC and EC decreased at days 7 and 21, respectively. Mammary FC
      and TG concentrations were diminished at day 14; incorporation of [3H]H2O into TG
      decreased at days 7 and 21, and incorporation of [3H]H2O into FC increased at day
      14. In the HT pups, growth rate was diminished, tetraiodothyronine concentration
      rose at days 7 and 14 of lactation, and triiodothyronine increased only at day
      14. Liver TG concentrations increased at day 7 and fell at day 14, while FC
      increased at day 14 and only acetyl CoA carboxylase activity fell at day 14.
      Thus, hyperthyroidism changed maternal liver and mammary lipid metabolism, with
      decreased lipid concentration in spite of increased liver rate of synthesis and
      decreases in mammary synthesis. These changes, along with the mild
      hyperthyroidism of the litters, may have contributed to their reduced growth
      rate.

PMID- 11592731
TI  - Evidence for specific ceramidase present in the intestinal contents of rats and
      humans.
AB  - A neutral ceramidase activity stimulated by bile salt was previously identified
      in the intestinal content. Recently, bile salt stimulated lipase (BSSL) was found
      to have ceramidase activity. It is unknown whether the ceramidase activity
      previously found is attributable to BSSL. To address this question, we compared
      the behaviors of high quaternary aminoethyl (HQ) anion exchange chromatography,
      the distributions, the stability, and the responses to lipase inhibitor between
      ceramidase and pancreatic BSSL. The proteins from whole small intestinal contents
      of humans and rats were precipitated by acetone and dissolved in 20 mM Tris
      buffer pH 8.2. These proteins had neutral ceramidase activity but not BSSL
      activity against p-nitrophenyl acetate. When the proteins were subject to HQ
      chromatography, two peaks of ceramidase activity were identified, which had acid
      and neutral pH optima, respectively. Neither of them had BSSL activity against p
      nitrophenyl acetate. Western blot using BSSL antiserum failed to identify BSSL
      protein in the fractions with high neutral ceramidase activity. In rat intestinal
      tract, pancreatic BSSL activity was high in the duodenum and declined rapidly in
      the small intestine, whereas neutral ceramidase activity was low in the duodenum
      and maintained a high level until the distal part of the small intestine. In
      addition, orlistat, the inhibitor of lipase, abolished human BSSL activity
      against p-nitrophenyl acetate and slightly reduced its activity against ceramide
      but had no inhibitory effect on ceramidase activity isolated by HQ
      chromatography. In conclusion, we provide the evidence for a specific ceramidase
      other than pancreatic BSSL present in the intestinal content. The enzyme may play
      important roles in digestion of dietary sphingolipids.

PMID- 11592732
TI  - Docosahexaenoic acid modulates phorbol ester-induced activation of extracellular
      signal-regulated kinases 1 and 2 in NIH/3T3 cells.
AB  - Phosphorylation of extracellular signal-regulated kinases (ERK1/ERK2) has been
      implicated in cell proliferation of mammalian cells. In the present study, we
      investigated the role of docosahexaenoic acid (DHA) in the modulation of
      ERK1/ERK2 phosphorylation, stimulated either with phorbol 12-myristate 13-acetate
      (PMA) or transforming growth factor-alpha (TGFalpha) in NIH/3T3 cells. We
      observed that both PMA and TGFalpha induced ERK1/ERK2 phosphorylation within 5
      min of stimulation. PMA acts upstream of MEK and via activation of protein kinase
      C (PKC), as GF109203X, a potent PKC inhibitor, and U0126, a MEK inhibitor,
      abolished its actions on ERK1/ERK2 phosphorylation. TGFalpha did not act via PKC
      because GF109203X failed to curtail the degree of ERK1/ERK2 phosphorylation in
      these cells. DHA alone failed to induce the phosphorylation of these mitogen
      activated protein (MAP) kinases; however, this fatty acid significantly curtailed
      the PMA- but not TGFalpha-induced MAP kinase enzyme activity and phosphorylation
      in NIH/3T3 cells. Furthermore, we observed that DHA significantly inhibited PMA
      induced translocation of two PKC isoforms, PKC alpha and PKC epsilon, from
      cytosol to plasma membrane. Interestingly, DHA failed to inhibit the PMA-induced
      translocation PKC delta isoform in these cells. Furthermore, DHA decreased PMA
      induced proliferation of NIH/3T3 cells. In this study, we show for the first time
      that DHA inhibits MAP kinase ERK1/ERK2) activation and proliferation of NIH/3T3
      cells via its inhibitory action on PKC alpha and epsilon isoforms.

PMID- 11592733
TI  - Incubation of lipid emulsions with plasma lipoproteins modifies the fluidity of
      each particle.
AB  - Lipid emulsions (LE) contain triglyceride (TG)-rich particles (TGRP) and
      phospholipid-rich particles (PLRP). Various lipid and protein exchanges take
      place during in vitro incubations of LE with lipoproteins. These composition
      changes affect physical properties of particles. The aim of this study was to
      determine the role of different LE particles and the effect of TG composition on
      physical modifications. Low density lipoproteins (LDL: 1.025 < d < 1.040 g/mL) or
      high density lipoproteins (HDL: 1.085 < d< 1.150 g/mL) were incubated with the
      following four LE or their TGRP or PLRP, which were manufactured with the same
      phospholipid emulsifier: long-chain triglycerides (LCT): 100% soybean oil; medium
      chain triglycerides (MCT)/LCT (MCT/LCT, 5:5, w/w); FO (100% fish oil); and MLF541
      (MCT/LCT/FO, 5:4:1, by wt). After incubation, modified LE particles and
      lipoproteins were analyzed by fluorescence polarization. Observed physical
      modifications were significant in emulsion particles (ordering effect) but not in
      lipoproteins and also were significant for TG composition effect. Since intact
      emulsion contained a large excess of TGRP over PLRP, it is not surprising that
      intact emulsion had the same behavior as TGRP alone, and that PLRP had the same
      physical characteristics as lipoproteins. TG loss and cholesterol and protein
      acquisitions by emulsion particles rigidify their envelope. The two emulsions
      containing FO were less ordered after incubation. In conclusion, incubation of LE
      with lipoproteins changes physical properties of each kind of particle, and TG
      composition of the emulsion affects emulsion particle changes but has no effect
      on LDL and HDL. These order modifications induce more effective exchanges between
      LE particles and lipoproteins and modify their metabolism; HDL changes may
      increase the reverse cholesterol transport.

PMID- 11592734
TI  - Comparative studies on individual isomeric 18:1 acids in cow, goat, and ewe milk
      fats by low-temperature high-resolution capillary gas-liquid chromatography.
AB  - The trans- as well as the cis-18:1 isomer profiles were established in cow, goat,
      and ewe cheese fats, with the assumption that these are representative of the
      corresponding milks. Argentation thin-layer chromatography was combined with low
      temperature high-resolution gas-liquid chromatography on 100-m highly polar
      capillary columns, thus adding precision to earlier data for these species.
      Despite differences in the absolute content of trans-18:1 isomers between
      species, the relative profiles were essentially similar. Except for the minor
      trans delta6-delta8 group, all trans-18:1 isomers with their ethylenic bonds
      between positions delta4 and delta16 (including the resolved critical pair
      delta13/delta14) were separated and quantitated individually. As expected,
      vaccenic (trans delta9-18:1) acid was the main isomer, accounting for as much as
      37 to 50% of the total fraction. It was observed that the goat trans-18:1 isomer
      profile was usually rather close to that of cows in winter (barn feeding),
      whereas that of the ewe shows a seasonal dependence. The trans-18:1 profile of
      ewe milk fats from this study resembles that of cows in the transition period
      between winter and summer (pasture) feeding. Regarding the cis-18:1 acid
      fraction, two isomers (oleic and cis-vaccenic acids) accounted for ca. 97% of
      that fraction for the three species, with the cis-delta12 isomer ranked third.
      The analytical procedure employed here appears a convenient alternative to
      oxidative-based procedures (generally ozonolysis), taking less time and
      alleviating some drawbacks of the latter procedure.

PMID- 11592735
TI  - Enrichment of eggs with n-3 polyunsaturated fatty acids: effects of vitamin E
      supplementation.
AB  - Eggs enriched with n-3 polyunsaturated fatty acids (PUFA) could contribute to
      dietary intake of these healthful fatty acids (FA). Because n-3 PUFA are highly
      susceptible to peroxidation, a first part of the study with Leghorn laying hens
      was carried out to investigate the influence of different levels of fish oil (0,
      0.7, 1.4, 2.8, or 5.6%, respectively) in the diet on n-3 PUFA, cholesterol,
      vitamin E, and lipid peroxidation product contents in eggs. Addition of fish oil
      to a complete diet based on wheat, rye, tapioca, and soybean constituents
      containing 11 IU vitamin E/kg resulted in increased n-3 PUFA content in egg yolk,
      mainly due to accumulation of docosahexaenoic acid. Cholesterol was not altered
      up to 2.8% fish oil in the diet. The vitamin E content of the yolk was
      insufficient for the protection of PUFA from peroxidation. Addition of up to 2.8%
      fish oil to laying hen diets increased the n-3 PUFA content of yolks with a
      concomitant imbalance between vitamin E and PUFA, leading to increased levels of
      cytotoxic aldehydic lipid peroxidation products such as malondialdehyde (MDA). In
      a second part of the studies, the balance between vitamin E, PUFA, and lipid
      peroxidation was analyzed during the period of storage of n-3 PUFA-enriched eggs
      produced after feeding the laying hens with 1.5% fish oil diets with different
      concentrations of vitamin E (0, 5, 10, 20, 40, 80, 160 IU/kg). Storage of eggs
      resulted in a marked loss of vitamin E in yolk. In stored eggs, the cytotoxic
      lipid peroxidation products MDA, 4-hydroxynonenal, and 4-hydroxyhexenal were
      reduced in response to vitamin E supplementation. To prevent the increase of
      cytotoxic aldehydic lipid peroxidation during production and storage of n-3 PUFA
      enriched eggs, a high vitamin E supplementation with at least 80 IU vitamin E/kg
      is needed.

PMID- 11592736
TI  - Diferuloylputrescine and p-coumaroyl-feruloylputrescine, abundant polyamine
      conjugates in lipid extracts of maize kernels.
AB  - Extraction of corn bran or corn fiber with polar solvents such as methylene
      chloride, ethanol or chloroform/methanol yielded common lipids and two unknown
      high-performance liquid chromatography (HPLC) peaks, each with an ultraviolet
      absorbance maximum at 320 nm. HPLC-mass spectrometry revealed that the unknowns
      were diferuloylputrescine (DFP) and p-coumaroyl-feruloylputrescine (CFP). When
      compared to extracts of corn fiber (a pericarp-enriched fraction from the wet
      milling of corn), comparable extracts of corn bran (a pericarp- enriched fraction
      from the dry milling of corn) yielded three- to eightfold higher levels of DFP
      and CFP. Extraction of corn bran or fiber with an accelerated solvent extractor
      revealed that elevated temperatures greatly enhanced the extraction of DFP and
      CFP by methylene chloride and ethanol. "Corn bran oil," prepared by extraction of
      corn bran with hot methylene chloride, contained 14 wt% DFP and 3 wt% CFP.
      However, when hexane was used as a solvent, accelerated solvent extraction of the
      corn bran or fiber did not extract any DFP or CFP. Extraction of wheat bran or
      psyllium hulls with hot methylene chloride did not yield any detectable DFP or
      CFP. Because it has been suggested that polyamine conjugates such as DFP and CFP
      may function as natural pesticides, a rapid method was developed to purify them
      so that their biological activity could be evaluated.

PMID- 11592737
TI  - The genus Thapsia as a source of petroselinic acid.
AB  - We describe the results from the isolation and structural identification of the
      acylglycerol constituents of fruits from wild plants belonging to different
      species of Thapsia (Apiaceae). The isolated lipid fractions were analyzed and
      characterized by chemical, chromatographic, and spectroscopic means. In
      particular, 13C nuclear magnetic resonance data allowed the identification of
      petroselinic acid as the major fatty acid esterified to glycerol in the fruit
      oils from all the plant samples. This was also confirmed by gas chromatography
      (GC) and GC-mass spectrometry analyses of fatty acid methyl and butyl esters
      derivatives from Thapsia oil. The genus Thapsia should be regarded as a useful
      source for the extraction of petroselinic acid, which represents an important
      oleochemical raw material.

PMID- 11592739
TI  - Prevention: whose responsibility is it?

PMID- 11592738
TI  - Characterization of lipoxygenase oxidation products by high-performance liquid
      chromatography with electron impact-mass spectrometric detection.
AB  - Lipoxygenase (LOX) is an enzyme that oxygenates polyunsaturated fatty acids to
      their corresponding hydroperoxy derivatives. For example, LOX found in plants
      produce the corresponding 13- and 9-hydroperoxide derivatives of linoleic acid
      (13-HPOD and 9-HPOD). Identification of the HPOD products is usually accomplished
      by using gas chromatography with mass spectrometric (MS) detection, which
      requires extensive derivatization of the thermally unstable hydroperoxy group.
      Here we report a high-performance liquid chromatographic method in combination
      with electron impact (EI)-MS detection that separates and characterizes the HPOD
      isomers generated by soybean LOX type I oxygenation of linoleic (LA) and
      linolenic acids as well as HPOD products produced by photosensitized oxidation of
      LA. The method does not required derivatization of the hydroxyperoxide group, and
      location of its position can be determined by the EI-MS fragmentation pattern.
      The method has been used for the analysis of HPOD produced by action of partially
      purified LOX from the micro-alga Chlorella pyrenoidosa on LA. The study suggests
      the presence of two LOX isozymes in the micro-alga that oxygenate LA to its 13
      HPOD and 9-HPOD derivatives. Moreover, the 9-LOX isozyme under anaerobic
      conditions cleaves 13-HPOD to 13-oxo-tridecadienoic acid and pentane but does not
      cleave 9-HPOD.

PMID- 11592740
TI  - Prevention: who should pay for it?

PMID- 11592741
TI  - Melanoma 2001.

PMID- 11592742
TI  - Acute  pharyngeal infections.

PMID- 11592743
TI  - Insomnia: therapeutic approach.
AB  - Insomnia is a common complaint. Transient and short-term insomnias usually result
      from stress or the use of certain pharmaceuticals or drugs and may be managed by
      reduced caffeine use, behavioral means, and/or pharmacologic treatment. Long-term
      insomnia is often a symptom of a medical or psychiatric condition or a primary
      sleep disorder. A diagnostic workup is expected; treatment should focus on the
      causative condition, as well as addressing the sleep problem itself. Established
      medications for the symptomatic treatment of insomnia include benzodiazepines,
      zolpidem, zaleplon, and certain antidepressant or occasionally antihistaminic
      drugs.

PMID- 11592744
TI  - Sleep histories are seldom documented on a general medical service.
AB  - BACKGROUND: Sleep disorders are common, but the frequency of sleep history
      documentation in hospitalized patients is unknown. METHODS: We reviewed 442
      initial histories and physical examinations recorded by 122 house officers and 47
      medical students in 208 consecutive general medicine ward patients. RESULTS: Any
      reference to sleep was recorded in only 18 patients (9%), including 12 of 141
      (9%) with conditions associated with obstructive sleep apnea. Sleep histories
      were recorded more often in women (13% vs 4%) and less often than histories of
      cigarette smoking or alcohol use. Medical students recorded such histories more
      often than did house officers. Patients with sleep histories more often had pulse
      oximetry (78% vs 37%), pulmonary function testing (11% vs 1%), arterial blood gas
      analysis (67% vs 30%), or electrocardiograms (78% vs 49%). CONCLUSIONS: Sleep
      histories are documented infrequently in hospitalized patients. Patients with a
      recorded sleep history more often have tests that suggest increased concerns
      about cardiorespiratory risk and/or a different process of care.

PMID- 11592745
TI  - Anal melanoma: an aggressive malignancy masquerading as hemorrhoids.
AB  - Anal melanoma is a devastating malignancy easily confused with benign
      hemorrhoids. Physician unfamiliarity with this bleeding rectal lesion can lead to
      delays in diagnosis and therapy. Four cases of anal melanoma, all initially
      mistaken for hemorrhoids, have been documented in the past 4 years at our
      institution. Despite surgical intervention and chemoimmunotherapy, each patient
      succumbed to widely metastatic disease. Average survival was 15.2 months. The
      clinical, pathologic, surgical, and oncologic features of anal melanoma are
      reviewed to enhance physician recognition of this unusual anorectal disorder.

PMID- 11592746
TI  - Lemierre's syndrome.
AB  - We describe a 32-year-old woman who had temperatures increasing over 7 days from
      100.7 degrees F to 104.0 degrees F. She had an upper respiratory infection and
      swelling of the left side of the neck. She was diagnosed with Lemierre's
      syndrome.

PMID- 11592747
TI  - Erectile dysfunction: update and options in primary care.

PMID- 11592748
TI  - Hypertension 2001: how will JNC VII be different from JNC VI?

PMID- 11592749
TI  - Get a handle on resistance before it gets a handle on you: the PROTEKT US
      Surveillance Study. Prospective Resistant Organism Tracking and Epidemiology for
      Ketolide Telithromycin.

PMID- 11592750
TI  - Rheumatoid arthritis--update on new therapies.

PMID- 11592751
TI  - What's in a name change?

PMID- 11592752
TI  - Does a lipid clinic increase compliance with National Cholesterol Education
      Program Treatment Guidelines? Report of a case-matched controlled study.
AB  - Despite a national effort to promote measurement of cholesterol levels in adults,
      previous studies have shown that poor control is the norm. We sought to determine
      the effects of implementation of a structured lipid treatment program. Forty-one
      clinic-managed patients were matched with similar control patients. Clinic
      patients had more risk factors overall and therefore lower low-density
      lipoprotein (LDL) goals. They had significantly greater LDL reduction after the 6
      month visit, resulting in a lower final LDL level. The percentage of patients
      reaching the LDL goal recommended by the National Cholesterol Education Program
      (NCEP) was the primary endpoint of the study. The NCEP guidelines were followed
      more frequently within the clinic, and significantly more clinic patients were
      treated to NCEP LDL goal than control patients. When indicated, medication was
      more frequently used and titrated in clinic patients. This study shows the
      efficacy of an organized lipid treatment clinic in management of dyslipidemia.

PMID- 11592753
TI  - Prenatal screening for Tay-Sachs disease by Louisiana obstetricians: a survey
      study.
AB  - BACKGROUND: Tay-Sachs disease has been reported to be more prevalent in the Cajun
      population of Louisiana. METHODS: Questionnaires were mailed to 744
      obstetricians; 151 responded. RESULTS: Of the 151 responding physicians, 95 (63%)
      reported that they do not routinely screen their prenatal patients for Tay-Sachs
      disease. Of the 52 responding obstetricians in New Orleans, 29 (58%) offer
      screening; 8 of 23 obstetricians (32%) in Acadiana (southwest Louisiana) and 19
      of 72 (27%) of the remaining Louisiana obstetricians routinely screen their
      patients. Of 46 obstetricians in practice less than 10 years, 22 (48%) offer
      screening; of 105 in practice longer, 35 (33%) offer screening. Of 100
      obstetricians trained in Louisiana, 32 (32%) offer screening, compared with 25 of
      51 (49%) of those trained elsewhere. CONCLUSIONS: Most practicing obstetricians
      in Louisiana are not routinely offering Tay-Sachs screening to their prenatal
      patients. Screening may depend on location of practice, duration of practice, and
      place of training.

PMID- 11592754
TI  - Comorbid illness and the early detection of cancer.
AB  - BACKGROUND: Comorbidity may be associated with later detection of cancer.
      METHODS: Incident cases of colorectal, breast, and prostate cancer and melanoma
      were determined from the 1994 Florida state tumor registry (N = 32,074). The
      relationship between comorbidity and late stage at diagnosis was examined using
      multiple logistic regression. RESULTS: Patients with comorbid conditions had
      greater odds of late stage diagnosis for each of the four cancers (colorectal,
      melanoma, breast, and prostate). Higher mortality rates were observed among
      patients with comorbid illness, not as a result of later stage at diagnosis, but
      rather due to their underlying disease. CONCLUSIONS: Comorbidity was associated
      with later stage diagnosis. Further research is needed to determine mechanisms by
      which comorbidity might influence stage at diagnosis.

PMID- 11592755
TI  - Follow-up survey of children and adolescents with chest pain.
AB  - BACKGROUND: The purposes of this study were to identify the outcome of chest pain
      in children and to identify the incidence of recurrent chest pain and the need
      for further medical services. METHODS: A telephone survey was conducted of
      pediatric patients evaluated in the cardiology clinic for chest pain. RESULTS: In
      the majority of patients (53 of 55), chest pain was thought to be noncardiac in
      origin. Fifteen patients were offered therapy, and all followed the therapy. Most
      (10 of 15) thought the therapy was helpful. Forty-one (75%) were satisfied with
      the explanation given to them. Twenty-six had recurrent chest pain, 12 had pain
      that was severe, 13 thought the pain interfered with daily activities, and 10
      sought further medical care. With the secondary evaluation of chest pain, the
      diagnosis changed in 9 of 10 cases. CONCLUSION: Chest pain in children is
      generally benign. However, chest pain can be recurrent and severe, interfering
      with activities of daily life.

PMID- 11592756
TI  - Tooth and periodontal disease: a review for the primary-care physician.
AB  - Dental diseases are widespread and are often underrecognized and treated. Caries
      and periodontal disease are common dental conditions that cause the majority of
      tooth loss. Although these conditions are preventable, many persons do not
      receive regular dental care and have acute problems when seen by their physician.
      Dental diseases frequently affect patients with multiple systemic disorders,
      including autoimmune disorders, diabetes, and human immunodeficiency virus (HIV)
      infection. The presence of dental disease may trigger inflammatory responses and
      have systemic consequences. Since dental disease affects almost all individuals,
      physicians should be able to recognize common conditions such as caries,
      periodontal disease, pulpitis, and dental abscess. In addition to initiating
      treatment and appropriate dental referrals, physicians should be familiar with
      the management of antibiotics and medications in the perioperative period.
      Another important role for physicians is to help reduce the societal and economic
      impact of these diseases through patient education and prevention.

PMID- 11592757
TI  - Salvage surgery.
AB  - Salvage surgery is an essential method in the armamentarium of the surgeon caring
      for the severely injured patient. The patient in unstable condition with multiple
      abdominal injuries is a challenge, even to the most experienced trauma surgeon.
      The first priority should be to control major vascular injuries and other sources
      of bleeding that are immediately life-threatening. Often after massive blood
      loss, the deadly triad of hypothermia, acidosis, and coagulopathy is present.
      Additional time in the operating room often worsens these physiologic parameters
      and patient outcome. Once surgically correctable bleeding has been addressed,
      such patients are best served by cessation of the operation, packing of the
      abdomen, and transfer to the intensive care unit. Resuscitative steps should then
      be taken. Once the physiologic derangement has been corrected, the patient can
      undergo definitive operative procedures.

PMID- 11592758
TI  - Successful treatment of cryptococcal osteomyelitis and paraspinous abscess with
      fluconazole and flucytosine.
AB  - A patient with thoracic cryptococcal osteomyelitis was treated successfully with
      the combination of fluconazole and flucytosine. This is the first reported case
      of cryptococcal osteomyelitis successfully treated with fluconazole and
      flucytosine.

PMID- 11592759
TI  - Sarcoidosis manifested as hypercalcemic pancreatitis.
AB  - Sarcoidosis is a multisystem disease of unknown etiology and with protean
      manifestations. Pancreatic involvement is unusual, with only a few case reports
      in the literature. Granulomatous infiltration is the usual cause. This case
      report describes an unusual presentation of sarcoidosis as hypercalcemic
      pancreatitis.

PMID- 11592760
TI  - Intravascular lymphoma presenting with clinical features of cholecystitis.

PMID- 11592761
TI  - Striae gravidarum as a predictor of vaginal lacerations at delivery.

PMID- 11592762
TI  - Phase II study of S-1, a novel oral fluorouracil, in advanced non-small-cell lung
      cancer.
AB  - The purpose of this study was to evaluate the efficacy and safety of a novel oral
      anticancer fluoropyrimidine derivative, S-1, in patients receiving initial
      chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC).
      Between June 1996 and July 1998, 62 patients with NSCLC who had not received
      previous chemotherapy for advanced disease were enrolled in this study. 59
      patients (22 stage IIIB and 37 stage IV) were eligible for the evaluation of
      efficacy and safety. S-1 was administered orally, twice daily, after meals. 3
      dosages of S-1 were prescribed according to body surface area (BSA) so that they
      would be approximately equivalent to 80 mg m(-2)day(-1): BSA < 1.25 m(2), 40 mg
      b.i.d.; BSA> or =1.25 but <1.5 m(2); 50 mg b.i.d., and BSA> or =1.5 m(2): 60 mg
      b.i.d. One cycle consisted of consecutive administration of S-1 for 28 days
      followed by a 2-week rest period, and cycles were repeated up to 4 times. The
      partial response (PR) rate of the eligible patients was 22.0% (13/59); (95%
      confidence interval: 12.3-34.7%). A PR was observed in 22.7% (5/22) of the stage
      IIIB patients and 21.6% (8/37) of the stage IV patients. The median response
      duration was 3.4 months (1.1-13.7 months or longer). Grade 4 neutropenia was
      observed in one of the 59 patients (1.7%). The grade 3 or 4 toxicities consisted
      of decreased haemoglobin level in 1.7% of patients (1/59), neutropenia in 6.8%
      (4/59), thrombocytopenia in 1.7% (1/59), anorexia in 10.2% (6/59), diarrhoea in
      8.5% (5/59), stomatitis in 1.7% (1/59), and malaise in 6.8% (4/59), and their
      incidences were relatively low. There were no irreversible, severe or unexpected
      toxicities. The median survival time (MST) of all patients was 10.2 months (95%
      confidence interval: 7.7-14.5 months), and the one-year survival rate was 41.1%.
      The MST of the stage IIIB patients was 7.9 months, and that of the stage IV
      patients was 11.1 months. The one-year survival rates of the stage IIIB and IV
      patients were 30.7% and 47.4%, respectively. S-1 was considered to be an active
      single agent against NSCLC. Further study of S-1 with other active agents is
      warranted.

PMID- 11592763
TI  - A prognostic model for ovarian cancer.
AB  - About 6000 women in the United Kingdom develop ovarian cancer each year and about
      two-thirds of the women will die from the disease. Establishing the prognosis of
      a woman with ovarian cancer is an important part of her evaluation and treatment.
      Prognostic models and indices in ovarian cancer should be developed using large
      databases and, ideally, with complete information on both prognostic indicators
      and long-term outcome. We developed a prognostic model using Cox regression and
      multiple imputation from 1189 primary cases of epithelial ovarian cancer (with
      median follow-up of 4.6 years). We found that the significant (P< or = 0.05)
      prognostic factors for overall survival were age at diagnosis, FIGO stage, grade
      of tumour, histology (mixed mesodermal, clear cell and endometrioid versus serous
      papillary), the presence or absence of ascites, albumin, alkaline phosphatase,
      performance status on the ZUBROD-ECOG-WHO scale, and debulking of the tumour.
      This model is consistent with other models in the ovarian cancer literature; it
      has better predictive ability and, after simplification and validation, could be
      used in clinical practice.

PMID- 11592764
TI  - The treatment of advanced renal cell cancer with high-dose oral thalidomide.
AB  - Thalidomide is reported to suppress levels of several cytokines, angiogenic and
      growth factors including TNF-alpha, basic fibroblast growth factor (bFGF),
      vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). The resulting
      anti-angiogenic, immunomodulatory and growth suppressive effects form the
      rationale for investigating thalidomide in the treatment of malignancies. We have
      evaluated the use of high-dose oral thalidomide (600 mg daily) in patients with
      renal carcinoma. 25 patients (all men; median age, 51 years; range 34-76 years)
      with advanced measurable renal carcinoma, who had either progressed on or were
      not suitable for immunotherapy, received thalidomide in an escalating schedule up
      to a maximum dose of 600 mg daily. Treatment continued until disease progression
      or unacceptable toxicity were encountered. 22 patients were assessable for
      response. 2 patients showed partial responses (9%; 95% CI: 1-29), 7 (32%; 95% CI:
      14-55) had stable disease for more than 6 months and a further 5 (23%; 95% CI: 8
      45) had stable disease for between 3 and 6 months. We also measured levels of TNF
      alpha, bFGF, VEGF, IL-6 and IL-12 before and during treatment. In patients with
      SD > or = 3 months or an objective response, a statistically significant decrease
      in serum TNF-alpha levels was demonstrated (P = 0.05). The commonest toxicities
      were lethargy (> or = grade II, 10 patients), constipation (> or = grade II, 11
      patients) and neuropathy (> or = grade II, 5 patients). Toxicities were of
      sufficient clinical significance for use of a lower and well tolerated dose of
      400 mg in currently accruing studies.

PMID- 11592765
TI  - Adult height and risk of breast cancer: a possible effect of early nutrition.
AB  - The relationship of breast cancer to early reproductive development and height
      suggests that fetal and childhood nutrition may be important in its aetiology.
      Caloric restriction sufficient to reduce adult height may reduce breast cancer
      risk. During World War II (WWII) there was a marked reduction in average caloric
      intake in Norway that resulted in greater nutritional diversity. We hypothesized
      that a positive association between height and risk of breast cancer would be
      stronger among women who were born during this period than among women born
      before or after the war. A total of 25 204 Norwegian women were followed up for
      approximately 11 years, and 215 incident cases of breast cancer were registered.
      We found the strongest positive association between height and breast cancer
      among women born during WWII: women in the tallest tertile (>167 cm) had a
      relative risk of 2.5 (95% confidence interval = 1.2-5.5) compared with the
      shortest (< or = 162 cm). Among women born before or after the war we found no
      clear association with height. The association with height in the WWII cohort may
      imply a role for early nutrition in breast cancer aetiology.

PMID- 11592766
TI  - Lifetime physical activity and risk of breast cancer.
AB  - We conducted a case-control study of 394 women with breast cancer and 788 control
      women (91% response) to investigate the association of lifetime physical activity
      with mainly menopausal breast cancer risk. After controlling for potential
      confounders, the odds ratios (95% confidence intervals) for increasing quartiles
      of lifetime physical activity were 1.00 (referent), 0.91 (0.60-1.37), 0.91 (0.60
      1.39), and 1.10 (0.73-1.67), respectively; P, trend = 0.47. We also separately
      examined physical activity at ages 12-18, 19-34, 35-49 and > or =50 years; no
      significant trends were observed in any age group. These data do not support a
      role of physical activity in preventing breast cancer.

PMID- 11592767
TI  - HPV types and cofactors causing cervical cancer in Peru.
AB  - We conducted a hospital-based case-control study in Peru of 198 women with
      histologically confirmed cervical cancer (173 squamous cell carcinomas and 25
      cases of adenocarcinoma/adenosquamous carcinoma) and 196 control women.
      Information on risk factors was obtained by personal interview. Using PCR-based
      assays on exfoliated cervical cells and biopsy specimens, HPV DNA was detected in
      95.3% of women with squamous cell carcinoma and in 92.0% of women with
      adenocarcinoma/adenosquamous carcinoma compared with 17.7% in control women. The
      age-adjusted odds ratio was 116.0 (95% Cl = 48.6-276.0) for squamous cell
      carcinoma and 51.4 (95% Cl = 11.4-232.0) for adenocarcinoma/adenosquamous
      carcinoma. The commonest types in women with cervical cancer were HPV 16, 18, 31,
      52 and 35. The association with the various HPV types was equally strong for the
      two most common types (HPV 16 and 18) as for the other less common types. In
      addition to HPV, long-term use of oral contraceptives and smoking were associated
      with an increased risk. HPV is the main cause of both squamous cell carcinoma and
      adenocarcinoma in Peruvian women.

PMID- 11592768
TI  - Long-lasting reduction of risk of colorectal cancer following screening
      endoscopy.
AB  - Several studies have suggested that incidence and mortality of colorectal cancer
      (CRC) may be strongly reduced for up to 10 years by endoscopic screening with
      removal of precancerous lesions, but so far there are no data on risk reduction
      beyond this period. We assessed long-term reduction of CRC risk following
      screening endoscopy in a statewide population-based case-control study in
      Saarland, Germany. Lifetime history of screening endoscopy was compared between
      320 cases with CRC aged 45-80 and 263 controls with other forms of cancer
      recruited from the same population. Potential confounding factors were controlled
      for by multiple logistic regression. 11% of cases compared to 27% of controls had
      a history of endoscopy for screening purposes (adjusted odds ratio (OR) = 0.28,
      95% confidence interval (CI): 0.16-0.48). This strong risk reduction was also
      seen (OR = 0.41, 95% CI: 0.19-0.89) in subjects who had their last screening
      endoscopy more than 10 years ago (median: 18.9 years). Long term (> 10 years
      since last screening) risk reduction appeared to be particularly strong for
      advanced (Dukes C or D) CRC (OR = 0.19, 95% CI: 0.06-0.64). We conclude that risk
      reduction by screening endoscopy is long lasting, in particular with respect to
      advanced CRC.

PMID- 11592769
TI  - Are retinol, vitamin C, vitamin E, folate and carotenoids intake associated with
      bladder cancer risk? Results from the Netherlands Cohort Study.
AB  - In the Netherlands Cohort Study among 120 852 subjects aged 55-69 years at
      baseline (1986), the association between vitamins and carotenoids intake, vitamin
      supplement use, and bladder cancer incidence was examined. Exposure status was
      measured with a food-frequency questionnaire. After 6.3 years of follow-up, data
      from 569 cases and 3123 subcohort members were available for case-cohort
      analyses. The age-, sex-, and smoking-adjusted relative risks (RRs) for retinol,
      vitamin E, folate, a-carotene, b-carotene, lutein and zeaxanthin, and lycopene
      were 1.04, 0.98, 1.03, 0.99, 1.16, 1.11, and 1.08, respectively, comparing
      highest to lowest quintile of intake. Only vitamin C (RR: 0.81, 95% CI: 0.61
      1.07, P-trend = 0.08), and b-cryptoxanthin intake (RR: 0.74, 95% CI: 0.53-1.03, P
      trend < 0.01) were inversely associated with bladder cancer risk. The association
      with vitamin C disappeared after adjustment for b-cryptoxanthin but not vice
      versa. The RRs for supplemental use of vitamin A, C or E compared to no use were
      around unity. We conclude that dietary or supplemental intake of vitamin A,
      vitamin C, vitamin E, and intake of folate, and most carotenoids are not
      associated with bladder cancer. In this study, only b-cryptoxanthin intake
      appeared to be inversely associated.

PMID- 11592770
TI  - Obesity and renal cell cancer--a quantitative review.
AB  - Obesity has been associated with an increased risk of renal cell cancer among
      women, while the evidence for men is considered weaker. We conducted a
      quantitative summary analysis to evaluate the existing evidence that obesity
      increases the risk of renal cell cancer both among men and women. We identified
      all studies examining body weight in relation to kidney cancer, available in
      MEDLINE from 1966 to 1998. The quantitative summary analysis was limited to
      studies assessing obesity as body mass index (BMI, kg m(-2)), or equivalent. The
      risk estimates and the confidence intervals were extracted from the individual
      studies, and a mixed effect weighted regression model was used. We identified 22
      unique studies on each sex, and the quantitative analysis included 14 studies on
      men and women, respectively. The summary relative risk estimate was 1.07 (95% CI
      1.05-1.09) per unit of increase in BMI (corresponding to 3 kg body weight
      increase for a subject of average height). We found no evidence of effect
      modification by sex. Our quantitative summary shows that increased BMI is equally
      strongly associated with an increased risk of renal cell cancer among men and
      women.

PMID- 11592771
TI  - Insulin-like growth factor-I and prostate cancer: a meta-analysis.
AB  - Some, but not all, epidemiological found have shown that high circulating levels
      of insulin-like growth factor-I (IGF-I) are associated with an increased risk of
      prostate cancer. We performed a meta-analysis on all the studies reported so far
      to evaluate this association. In our Medline search, 14 case-control studies were
      identified. A standard protocol abstracted information for each study. Hedges'
      standardized mean difference (HSMD) and odds ratio (OR) were used to estimate the
      effect of IGF-I and IGF-binding proteins (IGFBP-3). The combined data showed that
      circulating levels of IGF-I were significantly higher in prostate cancer patients
      (HSMD = 0.194). The OR for prostate cancer was 1.47 (95% confidence interval (CI)
      1.23-1.77) among men with high IGF-I compared to those with low IGF-I. The OR was
      1.26 (95% CI 1.03-1.54) for IGFBP-3. Circulating levels of IGF-I and IGFBP-3 are
      likely to be higher in prostate cancer patients than in the controls. These
      findings support the suggestion that high IGF-I and IGFBP-3 are associated with
      an increased risk of prostate cancer.

PMID- 11592772
TI  - Second primary neoplasms among 53 159 haematolymphoproliferative malignancy
      patients in Sweden, 1958-1996: a search for common mechanisms.
AB  - The Swedish Family-Cancer Database was used to analyse site-specific risk of
      second primary malignancies following 53 159 haematolymphoproliferative disorders
      (HLPD) diagnosed between 1958 and 1996. Standardized incidence ratio (SIR) of a
      second malignancy was calculated as the ratio of observed to expected numbers of
      second malignancies by applying site-, sex-, age-, period-, residence- and
      occupation-specific rates in the corresponding population in the Database to the
      appropriate person-years at risk. Among 18 960 patients with non-Hodgkin's
      lymphoma (NHL), there was over a 3-fold significant increase in cancer of the
      tongue, small intestine, nose, kidney and nervous system, squamous cell carcinoma
      (SCC) of the skin, NHL, Hodgkin's disease (HD) and lymphoid and myeloid
      leukaemia. Among 5353 patients with HD, there was over a 4-fold significant
      increase in cancer of the salivary glands, nasopharynx and thyroid, NHL and
      myeloid leukaemia, and over a 1.6-fold increase in cancer of the stomach, colon,
      lung, breast, skin (melanoma and SCC), nervous system and soft tissues and
      lymphoid leukaemia. Among 28 846 patients with myeloma and leukaemia, there was a
      significant increase in cancer of the skin, nervous system and non-thyroid
      endocrine glands and all HLPD except for myeloma. Our findings showed some
      clustering between first and second primaries among Epstein-Barr virus-,
      ultraviolet radiation- and immunosuppression-related cancers.

PMID- 11592773
TI  - Telomerase activity of the Lugol-stained and -unstained squamous epithelia in the
      process of oesophageal carcinogenesis.
AB  - Up-regulation of telomerase has been reported in many cancers. Our aim was to
      characterize telomerase activity in various states of the oesophagus to
      facilitate better understanding of carcinogenesis of oesophageal squamous cell
      carcinoma. During endoscopic examinations, we obtained 45 Lugol-stained normal
      epithelia, 31 Lugol-unstained epithelia (14 oesophagitis, 7 mild dysplasia, 5
      severe dysplasia and 5 intramucosal cancer) and 9 advanced cancer. Telomerase
      activity was semi-quantified by a telomeric repeat amplification protocol using
      enzyme-linked immunosorbent assay, and expression of human telomerase reverse
      transcriptase mRNA was examined by in situ hybridization. In the Lugol-stained
      normal epithelia, telomerase activity increased in proportion to the increase of
      severity of the accompanying lesions, with a rank order of advanced cancer,
      intramucosal cancer, mild dysplasia and oesophagitis. In the Lugol-unstained
      lesions and advanced cancer, telomerase activity was highest in advanced cancer.
      Up-regulation of telomerase in normal squamous epithelium may be a marker of
      progression of oesophageal squamous cell carcinoma.

PMID- 11592774
TI  - GalNAc glycoprotein expression by breast cell lines, primary breast cancer and
      normal breast epithelial membrane.
AB  - Over-expression of N-acetylgalactosamine glycoproteins as detected by binding of
      the lectin from Helix pomatia (HPA), is associated with metastatic competence and
      poor patient prognosis in a range of human adenocarcinomas. These glycoproteins
      remain poorly characterised, and their functional role has yet to be elucidated.
      This study describes characterisation of a range of human breast/breast cancer
      cell lines for the expression of the N-acetylgalactosaminylated glycoproteins of
      interest, and their comparison with normal breast epithelium and a range of
      clinical breast carcinoma samples. Confocal and light microscopy studies revealed
      cytochemical HPA-binding patterns consistent with a fundamental disruption in
      normal glycobiosynthetic pathways attending increasing metastatic potential. We
      report the most complete comparative analysis of HPA-binding ligands from
      cultured breast cells, clinical breast carcinoma samples and normal breast
      epithelium to date. Lectin blotting identified 11 major HPA-binding glycoprotein
      bands common to both clinical tumour samples and breast cell lines and 6 of these
      bands were also expressed by samples of normal breast epithelium, albeit at much
      lower levels. Moreover, very marked quantitative but not qualitative differences
      in levels of expression consistent with metastatic capability were noted.

PMID- 11592775
TI  - Expression of COX-2 and PGE synthase and synthesis of PGE(2)in endometrial
      adenocarcinoma: a possible autocrine/paracrine regulation of neoplastic cell
      function via EP2/EP4 receptors.
AB  - This study was designed to investigate the possible role of cyclo-oxygenase-2
      (COX-2) and prostaglandin E(2)(PGE(2)) in endometrial adenocarcinoma. COX-2 RNA
      expression was confirmed in various grades of adenocarcinoma by ribonuclease
      protection assay. COX-2 and microsomal glutathione-dependent prostaglandin E
      synthase (mPGES) expression and PGE(2)synthesis were localised to the neoplastic
      epithelial cells and endothelial cells. In order to establish whether PGE(2)has
      an autocrine/paracrine effect in adenocarcinomas, we investigated the expression
      of 2 subtypes of PGE(2)receptors, namely EP2 and EP4, by real time quantitative
      PCR. Expression of EP2 and EP4 receptors was detected in adenocarcinomas from all
      grades of differentiation and was significantly higher than that detected in
      normal secretory phase endometrium (P< 0.01). The fold induction of expression in
      adenocarcinoma compared with normal secretory phase endometrium was 28.0 +/- 7.4
      and 52.5 +/- 10.1 for EP2 and EP4 receptors respectively. Immunohistochemistry
      localised the site of expression of EP4 receptor in neoplastic epithelial cells
      and in the endothelium of carcinomas of all grades of differentiation. Finally,
      the functionality of the EP2/EP4 receptors was assessed by investigating cAMP
      generation following in vitro culture of adenocarcinoma tissue in the presence or
      absence of 300 nM PGE(2). cAMP production in response to PGE(2)was significantly
      higher in carcinoma tissue than that detected in normal secretory phase
      endometrium (3.42 +/- 0.46 vs 1.15 +/- 0.05 respectively; P< 0.001). In
      conclusion, these data suggest that PGE(2)may regulate neoplastic cell function
      in an autocrine/paracrine manner via the EP2/EP4 receptors.

PMID- 11592776
TI  - Carbonyl reductase as a significant predictor of survival and lymph node
      metastasis in epithelial ovarian cancer.
AB  - We have recently reported a novel function for carbonyl reductase (CR), namely,
      its ability to modulate the metastatic potential of malignant mouse cells.
      Because there are currently no data addressing a similar function for CR in human
      cancers, the aim of this study was to assess a correlation between survival and
      metastasis, and CR level in epithelial ovarian cancer. Using anti-CR antibody,
      immunohistochemical staining was performed on 73 epithelial ovarian cancers, 13
      borderline malignant tumours, and 25 benign ovarian tumours for a total of 111
      specimens. The combined rate for strongly and weakly positive reactions for CR
      was 32.0% for benign tumours, 38.5% for borderline malignant tumours, and 61.6%
      for ovarian cancers. The CR-positive rate was 35.7% (weakly positive alone) for
      ovarian cancers with retroperitoneal lymph node (RLN) metastasis and 67.8% for
      those without RLN metastasis (P< 0.05). The 5-year survival rate was 62.7% for
      the patients with CR-negative cancer and 86.1% for those with CR-positive cancer
      (P< 0.05). The present results indicate that decreased CR expression in
      epithelial ovarian cancer is associated with RLN metastasis and poor survival.

PMID- 11592777
TI  - Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western
      patients.
AB  - Colorectal carcinoma is uncommon in Egypt, but a high proportion of cases occurs
      before age 40 years and in the rectum. We compared the molecular pathology of 59
      representative Egyptian patients aged 10-72 to Western patients with sporadic,
      young-onset, or hereditary non-polyposis colorectal cancer syndrome (HNPCC)
      associated carcinoma and found significant differences. Most Egyptian cancers
      were rectal (51%) and poorly differentiated (58%). High levels of microsatellite
      instability (MSI-H) were frequent (37%) and attributable in some cases (36%) to
      methylation of the promoter of the hMLH1 mismatch repair gene, but no MSI-H
      cancer had loss of hMSH2 mismatch repair gene product of the type seen with
      germline hMSH2 mutation in HNPCC. K-ras mutation was uncommon (11%). In subset
      analyses, high frequencies of MSI-H in rectal carcinomas (36%) and p53 gene
      product overexpression in MSI-H cancers (50%) were found. MSI-H and K-ras
      mutation in Egyptians under age 40 were unusual (17% and 0%, respectively), and
      schistosomiasis was associated with MSI and K-ras mutation. Cluster analysis
      identified 2 groups: predominantly young men with poorly differentiated mucinous
      and signet-ring cell colorectal carcinoma lacking K-ras mutation; older patients
      who had well- or moderately differentiated adenocarcinoma often with MSI-H, K-ras
      mutation and schistosomiasis. Our findings show that the molecular pathology of
      colorectal cancer in older as well as younger Egyptians has unique differences
      from Western patients, and schistosomiasis influences the molecular pathogenesis
      of some tumours.

PMID- 11592778
TI  - Soluble Fas ligand released by colon adenocarcinoma cells induces host lymphocyte
      apoptosis: an active mode of immune evasion in colon cancer.
AB  - Expression of membrane-bound Fas ligand (mFasL) on colon cancer cells serves as a
      potential mechanism to inhibit host immune function by inducing apoptosis of host
      lymphocytes. Membrane-bound FasL can be cleaved and released as a soluble
      mediator (sFasL), which may spread the apoptosis induction effect. Our study
      examined whether colon adenocarcinoma cells release sFasL, and induce apoptosis
      of host lymphocytes without direct cell-cell contact. In 12 consecutive patients
      with colon adenocarcinoma mFasL was identified in the tumours, sFasL was measured
      in the sera and apoptosis identified in tumour-infiltrating and peripheral blood
      lymphocytes. To analyse the function of sFasL, colon cancer cells were primarily
      cultured; sFasL was isolated from supernatants, measured, incubated with Fas
      bearing Jurkat cells, and the resulting apoptosis was analysed. Serum levels of
      sFasL were significantly elevated in all colon cancer patients with mFasL
      expression in tumour tissues (n = 8). In these patients, the number of apoptotic
      lymphocytes was significantly increased within tumour and peripheral blood.
      Furthermore, sFasL was present in the corresponding supernatants and induced
      apoptosis of Jurkat cells in a dose-dependent manner. These findings suggest that
      mFasL-positive colon cancer cells release sFasL, and thus may induce apoptosis of
      host lymphocytes as a potential mechanism for immune evasion.

PMID- 11592779
TI  - Early to late sparing of radiation damage to the parotid gland by adrenergic and
      muscarinic receptor agonists.
AB  - Damage to salivary glands after radiotherapeutic treatment of head and neck
      tumours can severely impair the quality of life of the patients. In the current
      study we have investigated the early-to-late pathogenesis of the parotid gland
      after radiation. Also the ability to ameliorate the damage using pretreatment
      with adrenergic or muscarinic receptor agonists is studied. Rats were locally
      irradiated with or without i.p. pretreatment with phenylephrine (alpha
      adrenoceptor agonist, 5 mg kg(-1)), isoproterenol (beta-adrenoceptor agonist, 5
      mg kg(-1)), pilocarpine (4 mg kg(-1)), methacholine (3.75 mg kg(-1)) (muscarinic
      receptor agonists) or methacholine plus phenylephrine. Parotid salivary flow
      rate, amylase secretion, the number of cells and gland histology were monitored
      sequentially up to 240 days postirradiation. The effects were described in 4
      distinct phases. The first phase (0-10 days) was characterised by a rapid decline
      in flow rate without changes in amylase secretion or acinar cell number. The
      second phase (10-60 days) consists of a decrease in amylase secretion and is
      paralleled by acinar cell loss. Flow rate, amylase secretion and acinar cell
      numbers do not change in the third phase (60-120 days). The fourth phase (120-240
      days) is determined by a further deterioration of gland function but an increase
      in acinar cell number, albeit with poor tissue morphology. All drug pretreatments
      used could reduce radiation effects in phase I and II. The protective effects
      were lost during phase IV, with the exception of methacholine plus phenylephrine
      pretreatment. The latter combination of drugs ameliorated radiation-damage
      throughout the entire follow-up time. The data show that combined pre-irradiation
      stimulation of muscarinic acetylcholine receptors with methacholine plus alpha
      adrenoceptors with phenylephrine can reduce both early and late damage, possibly
      involving the PLC/PIP2 second messenger pathways. This opens perspectives for the
      development of clinical applicable methods for long-term sparing of parotid
      glands subjected to radiotherapy of head and neck cancer patients.

PMID- 11592780
TI  - A change in microsatellite instability caused by cisplatin-based chemotherapy of
      ovarian cancer.
AB  - To clarify the mechanism of acquired CDDP resistance in ovarian cancer, we
      compared the microsatellite instability (MSI) by the amplification of 10
      microsatellite loci and immunohistochemical detection of hMSH2 and hMLH1
      expression between the primary resected tumours and the secondary resected
      residual tumours after 5 or 6 courses of CDDP-based chemotherapy in the 24 cases
      of ovarian cancer. Of the 24 primary resected tumours, 9 (37.5%) showed MSI (7
      cases of MSI-L, 2 cases of MSI-H), while 15 (72.5%) were microsatellite stable
      tumours (MSS). The primary tumours also had MSI in the residual tumours after
      CDDP-based chemotherapy. However, all of the cases with MSS in the primary
      resected tumours exhibited MSI (2 cases were MSI-L, and 13 cases were MSI-H) in
      the residual tumours after CDDP-based chemotherapy (P< 0.001). Furthermore, 11
      (73.3%) of these cases which changed from MSS to MSI also had a change in the
      expression of hMLH1 from positive to undetectable (P< 0.001). Our data suggest
      that tumour MSI changes during CDDP-based chemotherapy, and that the loss of
      hMLH1 expression is one of the factors that has the greatest effect on this
      transformation.

PMID- 11592781
TI  - PDEPT: polymer-directed enzyme prodrug therapy. I. HPMA copolymer-cathepsin B and
      PK1 as a model combination.
AB  - Polymer-directed enzyme prodrug therapy (PDEPT) is a novel two-step antitumour
      approach using a combination of a polymeric prodrug and polymer-enzyme conjugate
      to generate cytotoxic drug selectively at the tumour site. In this study the
      polymeric prodrug N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-Gly-Phe-Leu
      Gly-doxorubicin conjugate PK1 (currently under Phase II clinical evaluation) was
      selected as the model prodrug, and HPMA copolymer-cathepsin B as a model for the
      activating enzyme conjugate. Following polymer conjugation (yield of 30-35%) HPMA
      copolymer-cathepsin B retained approximately 20-25% enzymatic activity in vitro.
      To investigate pharmacokinetics in vivo,(125)I-labelled HPMA copolymer-cathepsin
      B was administered intravenously (i.v.) to B16F10 tumour-bearing mice. HPMA
      copolymer-cathespin B exhibited a longer plasma half-life (free cathepsin B
      t(1/2alpha)= 2.8 h; bound cathepsin B t(1/2alpha)= 3.2 h) and a 4.2-fold increase
      in tumour accumulation compared to the free enzyme. When PK1 (10 mg kg(-1)dox
      equiv.) was injected i.v. into C57 mice bearing subcutaneously (s.c.) palpable
      B16F10 tumours followed after 5 h by HPMA copolymer-cathepsin B there was a rapid
      increase in the rate of dox release within the tumour (3.6-fold increase in the
      AUC compared to that seen for PK1 alone). When PK1 and the PDEPT combination were
      used to treat established B16F10 melanoma tumour (single dose; 10 mg kg(-1)dox
      equiv.), the antitumour activity (T/C%) seen for the combination PDEPT was 168%
      compared to 152% seen for PK1 alone, and 144% for free dox. Also, the PDEPT
      combination showed activity against a COR-L23 xenograft whereas PK1 did not.
      PDEPT has certain advantages compared to ADEPT and GDEPT. The relatively short
      plasma residence time of the polymeric prodrug allows subsequent administration
      of polymer-enzyme without fear of prodrug activation in the circulation and
      polymer-enzyme conjugates have reduced immunogenicity. This study proves the
      concept of PDEPT and further optimisation is warranted.

PMID- 11592783
TI  - Effect of exogenous melatonin on hepatic energetic status during
      ischemia/reperfusion: possible role of tumor necrosis factor-alpha and nitric
      oxide.
AB  - BACKGROUND: This study was designed to determine if the very potent antioxidant
      melatonin is able to reduce organ damage and improve energetic status in an in
      situ liver ischemia/reperfusion model. MATERIALS AND METHODS: Total hepatic
      ischemia was induced in rats by occlusion of the hepatic artery, portal vein, and
      bile duct. A portojugular shunt was inserted. After 60 min of ischemia,
      reperfusion was established for a period of 120 min. Rats were assigned to one
      group receiving systemic melatonin administration or to another receiving only
      normal saline. Variables were observed at preischemia, after 60 min of ischemia,
      and at 30, 60, and 120 min of reperfusion. RESULTS: Energy charge, measured as
      the arterial ketone body ratio, showed higher values in the melatonin group
      during the first 60 min of reperfusion. Rises in plasma nitrite, tumor necrosis
      factor (TNF)-alpha, aspartate aminotransferase, alanine aminotransferase, lipid
      peroxidation products, and inducible nitric oxide synthase (iNOS) expression were
      less severe with melatonin. Linear regression analysis demonstrated a significant
      correlation between nitrites and arterial ketone body ratio (R(2) = 0.2454). Bile
      production was higher with melatonin. Seven-day survival rates were 52% for
      control, 80% for melatonin, and 100% for sham groups. CONCLUSIONS: Exogenous
      melatonin is capable of preserving the functional and energetic status during
      ischemia/reperfusion which is associated with reduced concentrations of TNF-alpha
      and inhibited expression of iNOS and NO production. This improvement may be due
      to an adequate preservation of the hepatic mitochondrial redox status.

PMID- 11592782
TI  - Effects of the combination of camptothecin and doxorubicin or etoposide on rat
      glioma cells and camptothecin-resistant variants.
AB  - From the rat C6 glioma cell line in culture, we selected camptothecin-resistant
      variants by growth in the presence of increasing amounts of this drug (C6(CPT10),
      C6(CPT50)and C6(CPT100), growing respectively with 10, 50 and 100 ng ml(
      1)camptothecin). The degree of resistance to camptothecin ranged between 15-fold
      (C6(CPT10)) and 30-fold (C6(CPT50)and C6(CPT100)). The C6(CPT10)cell line
      presented a collateral sensitivity to etoposide (3.6-fold), while the
      C6(CPT50)and C6(CPT100)cell lines were cross-resistant to etoposide (1.8-fold)
      The resistant lines were characterised by a two-fold reduced content and
      catalytic activity of topoisomerase I, and C6(CPT50)and C6(CPT100)presented a
      significant increase in topoisomerase IIalpha content and catalytic activity and
      a marked overexpression of P-glycoprotein. We explored the cytotoxicity of
      combinations of a topoisomerase I inhibitor (camptothecin) and a topoisomerase II
      inhibitor (doxorubicin or etoposide) at several molar ratios, allowing the
      evaluation of their synergistic or antagonistic effects on cell survival using
      the median effect principle. The simultaneous combination of camptothecin and
      doxorubicin or etoposide was additive or antagonistic in C6 cells, slightly
      synergistic in the C6(CPT10)line and never more than additive in the C6(CPT50)and
      C6(CPT100)cell lines. The sequential combination of doxorubicin and camptothecin
      gave additivity in the order camptothecin --> doxorubicin and antagonism in the
      order doxorubicin --> camptothecin. Clinical protocols combining a topoisomerase
      I and a topoisomerase II inhibitor should be considered with caution because
      antagonistic effects have been observed with combinations of camptothecin and
      doxorubicin.

PMID- 11592784
TI  - Hypothermia induces T-cell production of immunosuppressive cytokines.
AB  - BACKGROUND: Hypothermia is associated with increased postoperative infectious
      complications. We hypothesized that hypothermia suppresses the inflammatory
      response by altering T-cell cytokine production from a proinflammatory to an
      antiinflammatory profile, thus explaining the increased susceptibility to
      infectious complications associated with perioperative hypothermia. METHODS:
      Forty rats were randomized to either a Hypothermia (30 degrees C) or Control (38
      degrees C) group. Blood samples taken at baseline and after 8 h of
      thermoregulation were stimulated with phorbol 12-myristate 13-acetate and
      ionomycin. Interleukin (IL)-2 receptor expression and intracellular IL-10
      production were measured using monoclonal antibodies and flow cytometry in CD4
      and CD8 T cells. Differences in IL-10 production and IL-2 receptor expression for
      stimulated samples in the Hypothermia and Control groups were compared. RESULTS:
      Stimulated CD4 cells demonstrated an antiinflammatory cytokine expression profile
      after hypothermia. Intracellular IL-10 production increased in the Hypothermia
      group but remained the same in the Control group (% change = 40 [3,87] and 2 [
      36,26], respectively; P = 0.043). The increase in IL-2 receptor expression
      observed in the control group was suppressed after hypothermia (% change =
      12[8,30] and 1 [-3,13], respectively; P = 0.026). We observed a greater increase
      in IL-10 production by CD8 cells from hypothermic animals than in those from
      control animals (% change = 41 [-8,90] and -4 [-40,5], respectively; P = 0.019).
      CD8 IL-2 receptor expression in hypothermic animals was similar to that of
      control animals (% change = 23 [-7,37] vs 25 [2,80], respectively; P = 0.32).
      CONCLUSIONS: Hypothermia induced an antiinflammatory T-cell cytokine profile.

PMID- 11592785
TI  - Bimodal concentration-dependent effect of thrombin on endothelial cell
      proliferation and growth factor release in culture.
AB  - BACKGROUND: The role of thrombin in the stimulation of endothelial cell (EC)
      proliferation is controversial. The aim of this study was to investigate if
      thrombin regulates cell proliferation and production of platelet-derived growth
      factor (PDGF), bovine fibroblast growth factor (bFGF), and transforming growth
      factor beta(1) (TGF-beta(1)) by bovine aortic ECs. METHODS: ECs, obtained from
      thoracic aortas of calves, were stimulated with thrombin at various
      concentrations (from 0.05 to 1.0 IU/ml) in serum free culture. Mitogenic activity
      of thrombin on ECs was determined by tritiated thymidine uptake. The release of
      PDGF, bFGF, and TGF-beta(1) was assessed by ELISA. PDGF release was confirmed by
      Western blot and bFGF and TGF-beta(1) mRNA expression was determined by
      polymerase chain reaction (PCR). RESULTS: Thrombin at high concentrations did not
      cause any increase in EC proliferation after 72 h of culture and induced
      inhibition of EC proliferation after 96 h and 8 days of culture. It induced a
      decrease in PDGF release and an increase in TGF-beta(1) release. Thrombin at low
      concentrations induced a significant increase in EC proliferation at 72 h, 96 h,
      and 8 days of culture. It induced an increase in PDGF release and a decrease in
      TGF-beta(1) release. bFGF release was higher than control at all thrombin
      concentrations. These data were confirmed by Western blot and PCR studies.
      CONCLUSIONS: Thrombin regulates EC growth through the inhibition of EC
      proliferation at high concentrations and through the stimulation of EC
      proliferation at low physiological concentrations. EC proliferation is partially
      mediated by autocrine production of PDGF, bFGF, and TGF-beta(1).

PMID- 11592786
TI  - Racial differences in breast cancer survival: the effect of residual disease.
AB  - BACKGROUND: A survival difference has been seen in numerous studies between
      African-American (AA) and Caucasian (C) women with breast cancer. The purpose of
      this study was to elucidate the differences in patient characteristics and
      outcomes between AA and C women with breast cancer in our population. METHODS: We
      performed a retrospective analysis of 1345 women with newly diagnosed breast
      cancer who were entered into our tumor registry from October 1980 to December
      1998. RESULTS: The association between race and stage at presentation was
      significant, as was the difference in the overall median survival between C and
      AA women. The data revealed no significant differences in survival between C and
      AA women presenting with Stage I or II disease. However, the differences between
      the median survival times for AA and C women presenting with Stage III and IV
      disease were both highly significant. A significantly lower percentage of AA
      women became "disease free" after initial therapy as compared with C women (P <
      0.001). Interestingly, when data were stratified by stage, only in Stage III and
      IV were there significant differences between the races for becoming disease
      free. CONCLUSIONS: AA women tend to present at a later stage and have poorer
      survival from later-stage disease as compared with C women. The poorer survival
      appears to be related to the decreased ability to achieve disease-free status in
      AA women with advanced disease. The underlying causes of this difference in
      treatment outcome need further evaluation.

PMID- 11592787
TI  - Cyclosporine directly causes oxidative stress and promotes Epstein-Barr virus
      transformation of human B cells.
AB  - BACKGROUND: We have previously shown that oxidative stress alone can promote
      transformation of human B cells infected with Epstein-Barr virus (EBV) in vitro,
      an accepted model mimicking posttransplant lymphoproliferative disorders (PTLDs).
      Our laboratory has investigated the direct effects of cyclosporine A (CyA) as an
      oxidant promoting B-cell transformation and we have proposed that CyA directly
      promotes B-cell transformation and that this effect can be blocked by
      antioxidants. METHODS: Human splenocytes were prepared by centrifugation and
      plating technique to provide a greater than 80% pure preparation of B cells that
      was used for the direct oxidative stress experiments. These cells were cocultured
      with CyA (500 ng/ml) and hydrogen peroxide (H(2)O(2), 0.15 mM) with or without
      antioxidant vitamin E (40 microM). Oxidative stress was evaluated by using a
      commercial lipid hydroperoxide (LPO) assay kit. In another set of three separate
      experiments, human B lymphocytes infected with EBV were cultured with CyA (500
      ng/ml), H(2)O(2) (0.15 mM), and vitamin E (40 microM). B-Cell transformation by
      EBV was evaluated by counting colony number and [(3)H]-thymidine incorporation.
      RESULTS: At therapeutic concentrations, CyA (500 ng/mL) had an oxidative effect
      on human splenocytes in vitro, similar to the effect of H(2)O(2) (90 and 97%
      increases, respectively in LPO production over control P < 0.005), which was
      abrogated by the addition of vitamin E. Similarly, both CyA and H(2)O(2) promoted
      transformation of B cells infected with EBV(75 and 108% increases respectively in
      colony counts over control, P < 0.005). This effect was also blocked by vitamin
      E. CONCLUSIONS: Both CyA and H(2)O(2) have a direct oxidative effect on human B
      cells and cause promotion of EBV-induced transformation of B cells. These effects
      are blocked by the antioxidant vitamin E. These findings may have future
      therapeutic implications for PTLDs.

PMID- 11592788
TI  - 1,25-(OH(2))D(3) alters the transforming growth factor beta signaling pathway in
      renal tissue.
AB  - BACKGROUND: 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) plays an important role
      in regulating immune responses, in addition to its effects on bone metabolism.
      The cytokine transforming growth factor beta (TGF-beta) regulates diverse
      biological processes, including cellular proliferation and differentiation,
      immune modulation, and modulation of extracellular matrix deposition. 1,25
      (OH)(2)D(3) interacts in vitro with Smad proteins, important regulators of TGF
      beta signal transduction. We hypothesized that exogenous 1,25-(OH)(2)D(3) would
      alter levels of TGF-beta(1) and TGF-beta(1) signaling proteins in renal tissue.
      METHODS: C57BL6 mice and Lewis rats were placed on diets with or without 1,25
      (OH)(2)D(3) for 14 days. Renal lysates were examined for TGF-beta(1), vitamin D
      receptor (VDR), and Smad3 protein levels using a cell proliferation assay and
      Western blot analysis. Coimmunoprecipitation was used to determine if any
      interaction between VDR and Smad3 proteins occurs in vivo. Reverse transcription
      polymerase chain reaction (RT-PCR) was used to assess messenger RNA (mRNA) levels
      for all of these molecules. RESULTS: Vitamin D supplementation decreased VDR and
      Smad3 protein levels. Coimmunoprecipitation of VDR and Smad3 revealed a Smad3-VDR
      interaction in vivo. Vitamin D-treated rats had a significant (P = 0.001)
      reduction in bioactive renal TGF-beta(1). RT-PCR demonstrated no difference in
      mRNA expression for either VDR or TGF-beta(1). CONCLUSION: Our results suggest
      that vitamin D has a significant effect in regulating levels of bioactive TGF
      beta(1) and appears to affect aspects of the TGF-beta(1) signaling system. These
      effects, in combination with the immunomodulatory actions of vitamin D, may alter
      the evolution of chronic rejection in renal transplants.

PMID- 11592789
TI  - Activator protein 1 activation following hypoosmotic stress in HepG2 cells is
      actin cytoskeleton dependent.
AB  - BACKGROUND: Following hypoosmotic stress-induced cell volume change, the actin
      cytoskeleton reorganizes itself. The role of this reorganization in the
      activation of the phosphatidylinositol 3-OH-kinase/protein kinase B/activator
      protein 1 (PI-3-K/PKB/AP-1) proliferative signaling cascade is unknown. Focal
      adhesion kinase (FAK) participates in the cytoskeleton-based activation of PI-3
      K. We hypothesized that hypoosmotic stress-induced activation of PKB and AP-1 in
      HepG2 cells is dependent on an intact actin cytoskeleton and subsequent FAK
      phosphorylation. METHODS: HepG2 cells were incubated for 1 h with or without 20
      microM cytochalasin D, an actin disrupter, and were then exposed for up to 30 min
      to hypoosmotic medium (200 mOsm/L) to induce swelling. Tumor necrosis factor
      alpha (1.4 nM) and medium alone served as positive and negative controls,
      respectively. Western blots measured cytoplasmic phosphorylated or total FAK and
      PKB. EMSAs measured nuclear AP-1. All experiments were performed in triplicate.
      RESULTS: Exposure to hypoosmotic stress resulted in activation of the following
      signaling messengers in a sequential fashion: (1) phosphorylation of FAK occurred
      by 2 min, (2) phosphorylation of PKB occurred by 10 min, (3) nuclear
      translocation of AP-1 occurred by 30 min. All three signaling events were
      abolished when these cells were pretreated with cytochalasin D. CONCLUSION: Actin
      reorganization following hypoosmotic stress is essential for the FAK-mediated
      activation of the PI-3-K/PKB/AP-1 proliferative cascade. These data delineate a
      possible mechanism by which the cell swelling-induced cytoskeletal changes can
      initiate proliferative signal transduction in human liver cancer.

PMID- 11592790
TI  - Therapeutic efficacy of the polymyxin-like peptide ranalexin in an experimental
      model of endotoxemia.
AB  - BACKGROUND: A rat model was used to investigate the efficacy of a polycationic
      peptide, the polymyxin-like ranalexin, in the prevention of lethality in a rat
      model of septic shock. The effect of ranalexin was compared with those of
      polymyxin B and imipenem. METHODS: Adult male Wistar rats (weight range: 250-300
      g) were used for all the experiments. The study included five groups: an
      uninfected control group C(0), an untreated control group C(1), and three drug
      treated groups that received 1 mg/kg ranalexin (group 2), 20 mg/kg imipenem
      (group 3), and 3 mg/kg polymyxin B (group 4). Rats, with the exception of the
      uninfected control group (C(0)), were given an intraperitoneal injection of 2 x
      10(10) colony-forming units of Escherichia coli. Each group included 15 animals.
      Bacterial growth in abdominal exudate and plasma; endotoxin and tumor necrosis
      factor alpha (TNF-alpha) concentrations in plasma, and mortality were evaluated.
      RESULTS: Results were evaluated 48 h after inoculation. Ranalexin, imipenem, and
      polymyxin B significantly reduced the lethality (survival was 93.3, 80.0, and
      93.3%, respectively) and the growth of E. coli both in abdominal fluid and plasma
      compared with saline treatment. Ranalexin showed higher antimicrobial activity
      than polymyxin B and imipenem and, at the same time, exhibited an antiendotoxin
      activity similar to that of polymyxin B (< or =0.015 EU/mL). Finally, ranalexin
      and polymyxin B significantly reduced plasma TNF-alpha levels (< or =4 pg/mL).
      CONCLUSION: Monodose ranalexin treatment prevents bacterial growth, endotoxemia,
      and mortality in rats with septic shock.

PMID- 11592791
TI  - Healing of traumatic diaphragm injuries: comparison of laparoscopic versus open
      techniques in an animal model.
AB  - BACKGROUND: Minimally invasive surgical techniques have become routinely applied
      to the evaluation and treatment of patients with isolated diaphragmatic injuries
      due to penetrating trauma. The objective of the study was to compare the healing
      of diaphragm injuries as determined by macroscopic inspection, histologic
      appearance, and tensile strength following repair by open suturing, laparoscopic
      suturing, and laparoscopic stapling techniques in an animal model. METHODS: Using
      a pig model, three injuries were created and repaired in each hemidiaphragm of
      five animals, for a total of 30 lacerations. These injuries were repaired using
      single-layer open repair, single-layer laparoscopic repair, or laparoscopic
      stapling. After a 6-week healing period the animals were sacrificed. The gross
      integrity, histologic appearance using H+E and trichrome satins, and tensile
      strength of each repair were assessed. RESULTS: All injuries were grossly intact
      without dehiscence or herniation. Histologic examination revealed no difference
      in the collagen deposition between the three groups. The tensile strengths of
      each type of repair were similar. CONCLUSION: Laparoscopic techniques used to
      repair diaphragmatic injuries allow for adequate healing equivalent to open
      sutured repairs. Simple approximation of the peritoneum with laparoscopic staples
      allows full-thickness healing of these injuries.

PMID- 11592792
TI  - Elevated intestinal fatty acid binding protein and gastrointestinal complications
      following cardiopulmonary bypass: a preliminary analysis.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) is associated with poorly understood
      alterations in gastrointestinal (GI) perfusion. Intestinal fatty acid binding
      protein (IFABP), a cytosolic protein uniquely located in mature small-intestinal
      enterocytes, has been shown to be a sensitive biochemical marker of early
      intestinal ischemia when assayed in urine. We hypothesized that if significant
      small-intestinal ischemia occurs with CPB, then urine IFABP levels should be
      concomitantly elevated. METHODS: Twenty-nine patients (15 low risk and 14 high
      risk) undergoing cardiac surgery with CPB were studied prospectively. Serial
      urine IFABP levels were measured and results were correlated with clinical
      outcomes. RESULTS: None of the low-risk patients had IFABP elevations or
      experienced GI complications. Five of the high-risk patients had IFABP
      elevations, and three of the five developed GI complications. Within the high
      risk cohort, the only significant difference between patients with or without
      IFABP elevations was the GI complication rate (P = 0.03). Overall, patients with
      IFABP elevations had a significantly higher mean ASA class and significant
      increases in mean CPB and aortic cross-clamp times, mean time to oral intake,
      median ICU and postoperative lengths of stay, and GI complications. CONCLUSIONS:
      In low-risk bypass patients, small-bowel mucosal perfusion appeared to be
      maintained, while in the high-risk population, 21% of the patients sustained
      clinically significant mucosal compromise. In this pilot study, urine IFABP was
      100% sensitive and 92% specific with respect to GI complications. Since elevated
      urine IFABP concentrations appeared to correlate with clinical GI complications,
      urine IFABP may be a useful marker to identify the patient at risk for postbypass
      GI complications.

PMID- 11592793
TI  - Rat aortic smooth muscle cell density affects activation of MAP kinase and Akt by
      menadione and PDGF homodimer BB.
AB  - Mitogen-activated protein kinases (MAPK) and protein kinase B (PKB or Akt) are
      major signal transduction molecules regulating cell proliferation,
      differentiation, and apoptosis. We examined how cultured rat aortic vascular
      smooth muscle cells (VSMC) at different cell densities respond to selected
      stimuli and how this is reflected in the two distinct (MAPK and Akt) and yet
      cross-talking signaling pathways. VSMC were cultured to 100% confluence, reaching
      contact inhibition, and to 60-70% confluence, as sparse, proliferating cells.
      They were treated with menadione (an intracellular generator of O(-2)) and/or
      platelet-derived growth factor homodimer BB (PDGF). In sparse cells, menadione or
      PDGF alone activated ERK, and together the effect was synergistic, whereas in
      confluent cells menadione's and PDGF's activations of ERK were, at most,
      additive. Activation of the upstream ERK kinase (MEK-1) paralleled ERK activation
      except in sparse cells in which the synergistic effects of menadione and PDGF on
      ERK could not be fully accounted for by MEK-1 activation. Another member of the
      MAPK family, p38, did not show significant changes. Akt activation by PDGF alone
      was present under both cell culture conditions; Akt activation is blocked by
      menadione. Co-incubation with the reducing agent dithiothreitol or calcium
      chelators (EDTA/EGTA) inhibited partially or completely menadione's effects on
      MEK/ERK and Akt pathways, as well as menadione's effects on PDGF-induced ERK and
      Akt activations. These data suggest that in VSMC, the state of cell confluence
      determines how distinct pathways of MAPK activation cross talk. In addition while
      PDGF may function as a survival factor by inducing Akt activation, menadione
      could promote apoptosis by inhibiting PDGF-induced Akt activation independent of
      cell density. The effects of menadione, but not those of PDGF, are more dependent
      on the cellular redox status and extracellular calcium.

PMID- 11592794
TI  - Fetal rat amniotic fluid: transforming growth factor beta and fibroblast collagen
      lattice contraction.
AB  - BACKGROUND: In several mammalian animal models, early-gestational-age fetal
      wounds heal without scar, but wounds of late gestational age heal with scar. This
      change in wound healing phenotype can be a result of both intrinsic (i.e.,
      cellular characteristics) and extrinsic (i.e., environmental) factors. Our
      question was: Does amniotic fluid (AF) influence the change from scarless to scar
      forming repair in the rat? METHODS: Rat AF was investigated for its modulation of
      fibroblast-populated collagen lattice (FPCL) contraction and morphological
      changes of adult fibroblasts. AF was also assayed for transforming growth factor
      beta (TGF-beta) levels. Adult rat dermal fibroblasts in monolayer and
      incorporated into FPCLs were incubated with AF additions from gestational age 14,
      16, 18, and 21 days at 10% (v/v). RESULTS: Day 14 AF significantly stimulated
      FPCL contraction, but AF of 16, 18, and 21 days inhibited FPCL contraction.
      Fluorescence histology identified microtubules and microfilaments in AF treated
      adult rat dermal fibroblasts. The staining pattern of microtubules in Day 14 AF
      treated fibroblasts showed denser structures at the cell center. Cells incubated
      with Day 16 or 18 AF showed fine peripheral microtubules. A mink lung epithelial
      cell bioassay was used to analyze concentrations of TGF-beta in AF. TGF-beta
      levels were greatly elevated in Day 14 AF, but were relatively low in Day 16, 18
      and 21 AF. The inhibitor of FPCL contraction from AF of Days 16, 18, and 21 was
      not identified. CONCLUSION: It is proposed that the robust expression of TGF-beta
      or cytoskeletal changes induced by Day 14 AF contributes to enhanced FPCL
      contraction.

PMID- 11592795
TI  - Effect of harvesting and sorting on beta-1 integrin in canine microvascular
      cells.
AB  - BACKGROUND: The goal of seeding prosthetic conduits with endothelial cells (ECs)
      has focused attention on the role of EC adhesion molecules. Cell preparation
      techniques may affect adhesion molecule expression and graft seeding. METHODS:
      Using fluorescent antibody labeling and flow cytometric analysis, this study
      examined the effectsof monolayer detachment (scraping vs trypsinization), timing
      of immunolabeling (pre- vs postdetachment), gene transfection (transfected vs
      nontransfected), and cell selection (antibiotic vs fluorescence sorting)
      techniques on beta-1 integrin expression in canine microvascular EC (K9MVEC).
      RESULTS: Cell scraping resulted in a significantly higher beta-1 integrin mean
      fluorescence intensity than did cell trypsinization (P < 0.05). No difference was
      observed with immunolabeling prior to versus following monolayer harvesting. Gene
      transfection had no significant effect on beta-1 integrin expression. No
      advantage was observed between cell selection methods (P > 0.05). CONCLUSION:
      This study suggests that the monolayer harvesting technique employed has a
      significant impact on beta-1 integrin quantification by flow cytometric analysis.
      Furthermore, microvascular EC expression of beta-1 integrin was not adversely
      affected by gene transfection.

PMID- 11592796
TI  - Prevention of postsurgical adhesions with an autocrosslinked hyaluronan
      derivative gel.
AB  - BACKGROUND: ACP gel is a new crosslinked derivative of hyaluronic acid (HA) that
      displays the biocompatibility properties of its original polymer but has a higher
      viscosity. It has been demonstrated in an animal model that the gel reduces
      adhesions after gynecological surgery. The aim of the present study was therefore
      to investigate the efficacy of ACP gel in increasing viscosity for the prevention
      of adhesions after abdominal surgery. METHODS: The antiadhesive effect of ACP gel
      was tested in a controlled randomized study using a standardized animal model of
      abdominal surgery involving the creation of defects in the parietal peritoneum
      and muscular fascia and cecal abrasion. The animals (100 female New Zealand white
      rabbits) were randomly allocated into five treatment groups to receive: ACP gel
      (1, 2, 4, and 6%) on the injured area or no ACP gel (control). The incidence of
      adhesions and their grade (score 0-11) were blindly evaluated 10 weeks after
      surgery. RESULTS: The percentages of adhesion-free animals were 60, 84, 90, and
      84% in the 1, 2, 4, and 6% ACP gel concentration groups, respectively, versus 15%
      in the control group (P = 0.001). The mean adhesion scores were 3.00 +/- 0.91,
      1.37 +/- 0.75, 0.65 +/- 0.45, and 1.16 +/- 0.64 in the 1, 2, 4, and 6% ACP gel
      groups, respectively, versus 7.70 +/- 0.83 in the control group (P < 0.001).
      CONCLUSION: ACP gel prevents postsurgical abdominal adhesions even at a 1%
      concentration. This finding may be of clinical importance in situations in which
      large volumes of antiadhesive solution are required.

PMID- 11592800
TI  - Inflammatory bowel disease. I. Genetic epidemiology.

PMID- 11592801
TI  - Inflammatory bowel disease. II. Gene mapping.

PMID- 11592802
TI  - Consequences of complexity within biological networks: robustness and health, or
      vulnerability and disease.

PMID- 11592803
TI  - Heterozygosity: an expanding role in proteomics.
AB  - The human genome sequence provides the framework for understanding the biology of
      human cell function. The next step is to intensify the investigation of protein
      function in the context of complex biological systems. Cellular functions are
      carried out by molecular complexes acting in concert rather than by single
      molecules or single reactions. Parallels have been drawn between scale-free
      nonbiologic networks and functionally interconnected metabolic pathways in the
      cell. Modeling of metabolic networks, in which functional modules or subnetworks
      represent individual related pathways, will lead to the prediction of protein
      function in the larger context of a complex system. Depending on the robustness
      of these metabolic networks, single-gene defects alone or in combination with
      other gene defects and the environment have the potential for invoking a spectrum
      of alterations in the integrity of a given network. The overall purpose of this
      review is to highlight the importance of simple heterozygosity for one pathogenic
      mutation or combinatorial heterozygosity for two or more mutations within or
      between individual genes in altering the stability of metabolic networks. Several
      forms of heterozygosity are considered, e.g., intra- and interallelic
      heterozygosity and double heterozygosity. The concepts of synergistic
      heterozygosity, loss of heterozygosity, and mitochondrial DNA heteroplasmy also
      are discussed in relation to the quantitative effects of coexisting mutations on
      the phenotypic expression of disease.

PMID- 11592804
TI  - U.S. newborn screening policy dilemmas for the twenty-first century.
AB  - Newborn screening has traditionally referred to biochemical testing for inherited
      disorders, generally metabolic in origin, that are usually correctable by dietary
      or drug interventions. As new tests have been developed, state public health
      newborn screening systems have slowly evolved without the benefit of national
      policies. Thus, newborn screening program changes, when viewed nationally, have
      been uncoordinated. The net result has been unequally applied mandated screening
      and, consequently, unequal availability of related public health disease
      prevention services. Technological advances in laboratory testing over the past
      10 years have resulted in limited program changes in some state newborn screening
      systems, and even greater program disparities. A recent Newborn Screening Task
      Force identified numerous issues of concern and proposed elements for a plan of
      action involving public health programs, healthcare providers, and consumers.
      This minireview details past policy history in newborn screening and identifies
      some of the current issues confronting programs as they seek to move ahead with
      the technologies and medical treatments for the twenty-first century.

PMID- 11592805
TI  - Dystrophin and muscular dystrophy: past, present, and future.
AB  - Duchenne muscular dystrophy was described in the medical literature in the early
      1850s but the molecular basis of the disease was not determined until the late
      1980s. The cloning of dystrophin led to the identification of a large complex of
      proteins that plays an important, although not yet well understood, role in
      muscle biology. Concomitant with the elucidation of the function of dystrophin
      and its associated proteins has been the pursuit of therapeutic options for
      muscular dystrophy. Although there is still no cure for this disorder, great
      advances are being made in the areas of gene introduction and cell transplant
      therapy.

PMID- 11592806
TI  - Fragile X syndrome: a model of gene-brain-behavior relationships.

PMID- 11592807
TI  - Genetic dissection of familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL) is the most common genetic hyperlipidemia
      in man. FCHL is characterized by familial clustering of hyperlipidemia and
      clinical manifestations of premature coronary heart disease, i.e., before the age
      of 60. Although FCHL was delineated about 25 years ago, at present the FCHL
      phenotype and its complex genetics are not fully understood. Initially, the
      familial aggregation of high plasma total cholesterol and triglyceride levels,
      with a bimodal distribution of triglycerides, was taken as evidence of a dominant
      mode of inheritance. However, it is now clear that the genetics of FCHL is more
      complex, and it has been suggested that FCHL is heterogeneous. Several approaches
      can be taken to identify genes contributing to the disease phenotype in complex
      genetic disorders either by studying the disease in the human situation or by
      using animal models. Recent reports have shown that a combination of genetic
      linkage studies, association studies, and differential gene expression studies
      provides a useful tool for the genetic dissection of complex diseases. Therefore,
      the genetic strategies that will be used to dissect the genetic background of
      FCHL are reviewed.

PMID- 11592808
TI  - Genetic disorders of cholesterol biosynthesis in mice and humans.
AB  - Over the past few years, the number of identified inborn errors of cholesterol
      biosynthesis has increased significantly. The first inborn error of cholesterol
      biosynthesis to be characterized, in the mid 1980s, was mevalonic aciduria. In
      1993, Irons et al. ( 1 ) (M. Irons, E. R. Elias, G. Salen, G. S. Tint, and A. K.
      Batta, Lancet 341:1414, 1993) reported that Smith-Lemli-Opitz syndrome, a classic
      autosomal recessive malformation syndrome, was due to an inborn error of
      cholesterol biosynthesis. This was the first inborn error of postsqualene
      cholesterol biosynthesis to be identified, and subsequently additional inborn
      errors of postsqualene cholesterol biosynthesis have been characterized to
      various extent. To date, eight inborn errors of cholesterol metabolism have been
      described in human patients or in mutant mice. The enzymatic steps impaired in
      these inborn errors of metabolism include mevolonate kinase (mevalonic aciduria
      as well as hyperimmunoglobulinemia D and periodic fever syndrome), squalene
      synthase (Ss-/- mouse), 3beta-hydroxysteroid Delta14-reductase (hydrops-ectopic
      calcification-moth-eaten skeletal dysplasia), 3beta-hydroxysteroid dehydrogenase
      (CHILD syndrome, bare patches mouse, and striated mouse), 3beta-hydroxysteroid
      Delta8,Delta7-isomerase (X-linked dominant chondrodysplasia punctata type 2,
      CHILD syndrome, and tattered mouse), 3beta-hydroxysteroid Delta24-reductase
      (desmosterolosis) and 3beta-hydroxysteroid Delta7-reductase (RSH/Smith-Lemli
      Opitz syndrome and Dhcr7-/- mouse). Identification of the genetic and biochemical
      defects which give rise to these syndromes has provided the first step in
      understanding the pathophysiological processes which underlie these malformation
      syndromes.

PMID- 11592809
TI  - Targeting tumor angiogenesis with gene therapy.
AB  - A recent target of cancer gene therapy is tumor angiogenesis. An appealing
      feature of gene therapy targeting the tumor vasculature is that it is readily
      accessible, particularly when the carrier and its gene are administered
      systemically. Several gene-based viral and nonviral therapies that target tumor
      angiogenesis have demonstrated the "proof of principle" of antiangiogenic therapy
      in preclinical models. The utility of antiangiogenic gene therapy in a clinical
      setting will depend in large part on developing vectors with minimal toxicity and
      with increased in vivo transfection efficiency. In this review, we discuss the
      current status and future directions of antiangiogenic gene therapy.

PMID- 11592810
TI  - Application of positron emission tomography for evaluation of metabolism and
      blood flow in human brain: normal development, aging, dementia, and stroke.

PMID- 11592811
TI  - Nonketotic hyperglycinemia (glycine encephalopathy): laboratory diagnosis.
AB  - Nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder of glycine
      metabolism caused by a defect in the glycine cleavage enzyme complex (GCS). GCS
      is a complex of four proteins encoded on four different chromosomes. In classical
      neonatal NKH, levels of cerebrospinal fluid (CSF) glycine and CSF/plasma glycine
      ratio are very high but the CSF results, in particular, may be more difficult to
      interpret in later-onset, milder, or otherwise atypical NKH. Enzymatic
      confirmation of NKH requires a liver sample. Delineation of which protein of the
      complex is defective is necessary to screen for mutations in the appropriate
      gene. Except for Finnish NKH patients, few recurrent mutations have yet been
      found, although analysis of the P-protein gene (the site of the defect in the
      majority of patients) is at an early stage. Prenatal diagnosis by GCS assay in
      chorionic villus biopsies is not completely reliable and will be replaced by
      molecular analysis in families where the mutations are known.

PMID- 11592812
TI  - Queuosine modification of tRNA: a case for convergent evolution.
AB  - Queuosine is a hypermodified nucleoside found in position 34, the anticodon
      wobble position, of four tRNA species. This modification is distributed with near
      uniformity across all life forms found on this planet. Yet the molecular
      mechanisms involved with accomplishing this ubiquitous posttranscriptional
      modification of tRNA are dramatically different between prokaryotic and
      eukaryotic organisms, which suggests that these were formed by convergent
      evolution of a fundamental life process essential to nearly all life forms. This
      minireview describes the differences between these modification systems and
      points to a new direction for developing research on the molecular function
      queuosine-modified tRNA in diverse species.

PMID- 11592813
TI  - Influences of adenosine on the fetus and newborn.
AB  - Few signaling molecules have the potential to influence the developing mammal as
      the nucleoside adenosine. In contrast to most neurotransmitters, adenosine is
      released by all cells and is present in all tissues. The adenosinergic system is
      therefore not dependent on the presence of mature synaptic structures or an
      intact autonomic nervous system for its release. However, similar to other
      signaling molecules, adenosine levels are dynamically regulated and increase with
      increased tissue activity, hypoxia, or stress. Local adenosine concentrations
      thus provide a "humoral barometer" of acute changes in cellular physiology. The
      receptors that transduce adenosine action include A1, A2a, A2b, and A3 adenosine
      receptors. These receptors differ in their affinities for adenosine and in
      patterns of tissues expression. During development A1 adenosine receptors (A1ARs)
      are especially important, and A1ARs are among the earliest receptors expressed in
      the embryonic brain and heart. In the developing heart, the adenosinergic system
      is the dominant regulator of fetal cardiac function and A1AR activation inhibits
      cardiac cell division leading to cardiac hypoplasia. In the forming central
      nervous system, A1AR activation potently inhibits the development of axons and
      can lead to leukomalacia. These recent data suggest that adenosine is an
      important modulator of mammalian development.

PMID- 11592814
TI  - Tetrahydrobiopterin deficiencies without hyperphenylalaninemia: diagnosis and
      genetics of dopa-responsive dystonia and sepiapterin reductase deficiency.
AB  - DOPA responsive dystonia (DRD) and sepiapterin reductase (SR) deficiency are
      inherited disorders of tetrahydrobiopterin (BH4) metabolism characterized by the
      signs and symptoms related to monoamine neurotransmitter deficiency. In contrast
      to classical forms of BH4 deficiency DRD and SR deficiency present without
      hyperphenylalaninemia and thus cannot be detected by the neonatal screening for
      phenylketonuria (PKU). While DRD is mostly caused by autosomal dominant mutations
      in the GTP cyclohydrolase I gene (GCH1), SR deficiency is an autosomal recessive
      disease. The most important biochemical investigations for the diagnosis of these
      neurological diseases includes CSF investigations for neurotransmitter
      metabolites and pterins as well as neopterin and biopterin production in cytokine
      stimulated fibroblasts. Discovery of SR deficiency opened new insights into
      alternative pathways of the cofactor BH4 via carbonyl, aldose, and dihydrofolate
      reductases. As a consequence of the low dihydrofolate reductase activity in the
      brain, dihydrobiopterin intermediate accumulates and inhibits tyrosine and
      tryptophan hydroxylases and uncouples nitric oxide synthase (nNOS), leading to
      neurotransmitter deficiency and possibly also to neuronal cell death.

PMID- 11592815
TI  - Sequence and functional analysis of GLUT10: a glucose transporter in the Type 2
      diabetes-linked region of chromosome 20q12-13.1.
AB  - We have carried out a detailed sequence and functional analysis of a novel human
      facilitative glucose transporter, designated GLUT10, located in the Type 2
      diabetes-linked region of human chromosome 20q12-13.1. The GLUT10 gene is located
      between D20S888 and D20S891 and is encoded by 5 exons spanning 26.8 kb of genomic
      DNA. The human GLUT10 cDNA encodes a 541 amino acid protein that shares between
      31 and 35% amino acid identity with human GLUT1-8. The predicted amino acid
      sequence of GLUT10 is nearly identical in length to the recently described GLUT9
      homologue, but is longer than other known members of the GLUT family. In
      addition, we have cloned the mouse cDNA homolog of GLUT10 that encodes a 537
      amino acid protein that shares 77.3% identity with human GLUT10. The amino acid
      sequence probably has 12 predicted transmembrane domains and shares
      characteristics of other mammalian glucose transporters. Human and mouse GLUT10
      retain several sequence motifs characteristic of mammalian glucose transporters
      including VP497ETKG in the cytoplasmic C-terminus, G73R[K,R] between TMD2 and
      TMD3 (PROSITE PS00216), VD92RAGRR between TMD8 and TMD9 (PROSITE PS00216),
      Q242QLTG in TMD7, and tryptophan residues W430 (TMD10) and W454 (TMD11), that
      correspond to trytophan residues previously implicated in GLUT1 cytochalasin B
      binding and hexose transport. Neither human nor mouse GLUT10 retains the full
      P[E,D,N]SPR motif after Loop6 but instead is replaced with P186AG[T,A]. A PROSITE
      search also shows that GLUT10 has lost the SUGAR TRANSPORT 2 pattern (PS00217), a
      result of the substitution G113S in TMD4, while all other known human GLUTs
      retain the glycine and the pattern match. The significance of this substitution
      is unknown. Sites for N-linked glycosylation are predicted at N334ATG between
      TMD8 and TMD9 and N526STG in the cytoplasmic C-terminus. Northern hybridization
      analysis identified a single 4.4-kb transcript for GLUT10 in human heart, lung,
      brain, liver, skeletal muscle, pancreas, placenta, and kidney. By RT-PCR
      analysis, GLUT10 mRNA was also detected in fetal brain and liver. When expressed
      in Xenopus oocytes, human GLUT10 exhibited 2-deoxy-D-glucose transport with an
      apparent Km of approximately 0.3 mM. D-Glucose and D-galactose competed with 2
      deoxy-D-glucose and transport was inhibited by phloretin. The gene localization
      and functional properties suggest a role for GLUT10 in glucose metabolism and
      Type 2 diabetes.

PMID- 11592816
TI  - Pancreatic islet transplantation for diabetes: successes, limitations, and
      challenges for the future.

PMID- 11592817
TI  - Expression profiles of COUP-TF, DAX-1, and SF-1 in the human adrenal gland and
      adrenocortical tumors: possible implications in steroidogenesis.
AB  - Chicken ovalbumin upstream promoter-transcription factor (COUP-TF), DAX-1, and
      steroidogenic factor-1 (SF-1) are orphan members of the nuclear hormone receptor
      superfamily. COUP-TF and DAX-1 have been shown to negatively regulate the
      transcriptional activity of SF-1, a steroidogenic cell-specific activator of
      various steroidogenic cytochrome P450 genes. We therefore examined the expression
      levels and immunolocalization of COUP-TF, DAX-1, and SF-1 in human adrenal gland
      (NL) and adrenocortical adenomas, and compared the results with CYP17 expression
      levels and its enzyme activities to study their potential correlation with
      adrenocortical steroidogenesis. In NL (n = 10), expressions of COUP-TF, DAX-1,
      and SF-1 were detected in the nuclei of adrenocortical cells, but not in the
      medulla. In cortisol-producing adenomas causing Cushing syndrome (CS, n = 20),
      CYP17 expression was upregulated (298 +/- 2% vs NL 98 +/- 4%), whereas expression
      levels of both COUP-TFs (COUP-TFI, 52 +/- 5% vs NL 98 +/- 4%; COUP-TFII, 18 +/-
      4% vs NL 98 +/- 4%) and DAX-1 (42 +/- 4% vs NL 100 +/- 4%) were reduced. In
      deoxycorticosterone-producing adenomas (DOC, n = 2), on the other hand, CYP17
      expression was extremely reduced (8 and 12% vs NL 98 +/- 4%), whereas DAX-1
      expression increased markedly (350 and 360% vs NL 100 +/- 4%). Expression levels
      of SF-1 did not differ between NL (100 +/- 8%) and CS (106 +/- 10%), but its
      expression appeared to be decreased in DOC (25 and 20%). These results showed
      CYP17 expression to be upregulated and downregulated in CS and DOC, respectively,
      in a manner reciprocal to that of its repressors, COUP-TF and/or DAX-1. In
      summary, the results indicate that co-localization of COUP-TF, DAX-1, and SF-1 in
      NL was lost in adrenocortical tumors and that these orphan receptors play an
      important role in the regulation of steroidogenesis in human adrenals.

PMID- 11592818
TI  - Characterization of the murine gene corresponding to human Hermansky-Pudlak
      syndrome type 3: exclusion of the Subtle gray (sut) locus.
AB  - Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism and a
      bleeding diathesis due to absent platelet dense bodies. In addition to exhibiting
      considerable phenotypic variation, this autosomal recessive disorder displays
      locus heterogeneity. One causative gene is HPS1, coding for a protein of unknown
      function and resulting in HPS-1 disease, common in northwest Puerto Rico. A
      second HPS-causing gene is ADTB3A, coding for the beta3A subunit of adaptor
      complex-3 (AP-3, a coat protein complex) and resulting in HPS-2 disease. Each of
      these HPS subtypes has a murine counterpart, specifically pale ear for HPS-1 and
      pearl for HPS-2. Recently, the HPS3 gene, responsible for HPS-3 disease in a
      genetic isolate of central Puerto Rico, was isolated and characterized. Its
      location on human chromosome 3q24 suggested that the mouse model corresponding to
      HPS-3 disease might be subtle gray. To examine this possibility, we determined
      the mouse HPS3 sequence, its genomic organization, and its amino acid sequence,
      which shares 95.8% identity with the human protein. We demonstrated that the
      subtle gray mouse produces a normal size and amount of HPS3 mRNA and has an
      entirely normal sequence in every exon and intron/exon boundary. Furthermore,
      subtle gray exhibits a normal contingent of platelet dense bodies. Together,
      these data eliminate subtle gray as a murine model for HPS-3 disease and suggest
      that other mouse models be examined.

PMID- 11592819
TI  - Arginine 387 of human isovaleryl-CoA dehydrogenase plays a crucial role in
      substrate/product binding.
AB  - Isovaleryl-CoA dehydrogenase (IVD) is a homotetrameric flavoenzyme, which
      catalyzes the conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA and transfers
      electrons to the electron-transferring flavoprotein, and is a member of the acyl
      CoA dehydrogenase (ACD) enzyme family. Human IVD crystal structure with a bound
      substrate analogue shows the guanidino group of Arg387, a conserved residue among
      other members of the ACD enzyme family, juxtaposed to a phosphate oxygen of the
      4'-phosphopantothiene moiety of the substrate analogue. Site-directed mutagenesis
      was used to investigate the role of Arg387 in substrate binding and enzyme
      function. Replacing this residue with Lys, Ala, Gln, or Glu resulted in stable
      proteins. Spectrophotometric substrate binding assays indicated that the
      Arg387Lys mutant was able to form the charge-transfer complex intermediate with
      similar efficiency to wild type, while the rest of the mutants were significantly
      less able to properly form this intermediate. However, the Km of the isovaleryl
      CoA for the Arg387Lys mutant was 20.3 compared to 1.5 microM for the wild type.
      The Km for the rest of the mutants were 75.6, 195, and 550 microM, respectively.
      The catalytic efficiency per mole of FAD was 20.3, 3.3, 2.0, and 0.34 for the
      mutants, respectively, compared to 260 microM(-1) x min(-1) for the wild type.
      These results substantiate the important role of Arg387 in anchoring the
      substrate, and are consistent with the hypothesis that residues distant from the
      active site are important for stabilizing the enzyme:substrate/product complex,
      and could play an important role in the mechanism of the enzyme-catalyzed
      reaction.

PMID- 11592820
TI  - Structure of the PCCA gene and distribution of mutations causing propionic
      acidemia.
AB  - Propionyl-CoA carboxylase (PCC, EC 6.4.1.3) is a mitochondrial, biotin-dependent
      enzyme that functions in the catabolism of branched-chain amino acids, fatty
      acids with odd-numbered chain lengths, and other metabolites. It catalyzes the
      ATP-dependent carboxylation of propionyl-CoA to d-methylmalonyl-CoA. PCC is
      composed of two types of subunits, likely as alpha4beta4 or alpha6beta6, with the
      alpha subunit containing the covalently bound biotin prosthetic group. A genetic
      deficiency of PCC activity causes propionic acidemia, a potentially fatal disease
      with onset in severe cases in the newborn period. Affected patients may have
      mutations of either the PCCA or PCCB gene. In this study, we have determined the
      structure of the human PCCA gene which, at the present time, is only partially
      represented in the databases. Based on reported ESTs and confirmed by RT-PCR, we
      also redefine the translation initiation codon to a position 75 nucleotides
      upstream of the currently accepted initiation codon. We show the distribution of
      mutations, including three identified in this study, and renumber all reported
      mutations to count from the new initiation codon. The gene spans more than 360 kb
      and consists of 24 exons ranging from 37 to 335 bp in length. The introns range
      in size from 104.bp to 66 kb. We have also determined the nucleotide sequence of
      approximately 1 kb of the 5'-flanking region upstream of the ATG translation
      initiation site. The proximal 400 bp of the 5'-flanking region shows a high G + C
      content (67%) and is part of a putative 1-kb CpG island that extends into exon 1
      and part of intron 1. The putative promoter lacks a TATA box but contains two AP
      1 sites and a conservatively defined consensus GC box, the latter characteristic
      of the core binding sequence of the Sp1 transcription factor.

PMID- 11592821
TI  - Aberrant mRNA splicing associated with coding region mutations in children with
      carnitine-acylcarnitine translocase deficiency.
AB  - This report describes three infants with genetic defects of carnitine
      acylcarnitine translocase (CACT), an inner mitochondrial membrane carrier that is
      essential for long-chain fatty acid oxidation. Two of the patients were of
      European and Chinese origin; the third was from consanguineous Turkish parents.
      CACT activity was totally deficient in cultured skin fibroblasts from all three
      patients. Patient 1 was heterozygous for a paternal frameshift mutation (120 del
      T in exon 1) and a maternal lariat branch point mutation (-10 T --> G in intron
      2). Patient 2 was heterozygous for the same lariat branch point (-10T --> G
      intron 2) mutation, derived from the father, and a maternal frameshift mutation
      (362 del G in exon 3). Patient 3 was homozygous for a frameshift mutation (306
      del C in exon 3). All of the three frameshift mutations give rise to the same
      stop codon at amino acid residue 127 which is predicted to cause premature
      protein truncation. In addition, cDNA transcript analysis showed that these
      coding sequence mutations also increase the amount of aberrant mRNA splicing and
      exon skipping at distances up to 7.7 kb nucleotides from mutation sites. The data
      suggest that the stability of mRNA transcripts is decreased or the frequency of
      aberrant splicing is increased in the presence of CACT coding sequence mutations.
      These results confirm that CACT is the genetic locus of the recessive mutations
      responsible for the fatal defects of fatty acid metabolism previously associated
      with deficiency of translocase activity in these three cases.

PMID- 11592822
TI  - Evaluation of pharmacological induction of fatty acid beta-oxidation in X-linked
      adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is an inherited neurometabolic disorder
      associated with elevated levels of saturated unbranched very-long-chain fatty
      acids (VLCFA; C > 22:0) in plasma and tissues, and reduced VLCFA beta-oxidation
      in fibroblasts, white blood cells, and amniocytes from X-ALD patients. The X-ALD
      gene (ABCD1) at Xq28 encodes the adrenoleukodystrophy protein (ALDP) that is
      related to the peroxisomal ATP-binding cassette (ABCD) transmembrane half
      transporter proteins. The function of ALDP is unknown and its role in VLCFA
      accumulation unresolved. Previously, our laboratory has shown that sodium 4
      phenylbutyrate (4PBA) treatment of X-ALD fibroblasts results in increased
      peroxisomal VLCFA beta-oxidation activity and increased expression of the X-ALD
      related protein, ALDRP, encoded by the ABCD2 gene. In this study, the effect of
      various pharmacological agents on VLCFA beta-oxidation in ALD mouse fibroblasts
      is tested. 4PBA, styrylacetate and benzyloxyacetate (structurally related to
      4PBA), and trichostatin A (functionally related to 4PBA) increase both VLCFA
      (peroxisomal) and long-chain fatty acid [LCFA (peroxisomal and mitochondrial)]
      beta-oxidation. Isobutyrate, zaprinast, hydroxyurea, and 5-azacytidine had no
      effect on VLCFA or LCFA beta-oxidation. Lovastatin had no effect on fatty acid
      beta-oxidation under normal tissue culture conditions but did result in an
      increase in both VLCFA and LCFA beta-oxidation when ALD mouse fibroblasts were
      cultured in the absence of cholesterol. The effect of trichostatin A on
      peroxisomal VLCFA beta-oxidation is shown to be independent of an increase in
      ALDRP expression, suggesting that correction of the biochemical abnormality in X
      ALD is not dependent on pharmacological induction of a redundant gene (ABCD2).
      These studies contribute to a better understanding of the role of ALDP in VLCFA
      accumulation and may lead to the development of more effective pharmacological
      therapies.

PMID- 11592823
TI  - Structure-function analyses of a common mutation in blacks with transferase
      deficiency galactosemia.
AB  - We previously identified a missense mutation at amino acid 135 of human galactose
      1-phosphate uridyltransferase (hGALT) in which a leucine (TTG) was substituted
      for a serine (TCG), S135L. This mutation was common in black patients with
      galactosemia and homozygotes (S135L/S135L) had no GALT activity or protein in
      their erythrocytes or lymphoblasts. However, there was residual GALT activity and
      protein in their leukocytes, and they had near normal total body [13C]galactose
      oxidation to 13CO2 in breath. To evaluate the biochemical mechanism(s) producing
      these effects, we overexpressed hGALT proteins with site-directed mutations in
      this nonconserved amino acid in a GALT-minus Escherichia coli. Enzyme activities
      detected in bacterial lysates overexpressing either S135 (wild type), A135, C135,
      H135, L135, S132-H135, T135, or Y135 were 100, 4.7, 3.0, 4.0, 2.7, 0.7, 35.4, and
      1.4%, respectively. Only the threonine substitution (S135T) had significant
      enzyme activity in these lysates. There was also decreased abundance of all
      mutant proteins in the lysates exposed to bacterial proteolysis during
      preparation and analysis. This added the variable of bio-instability to analysis
      of enzyme activities in lysates. To further characterize the catalytic role of
      serine at amino acid 135 and to differentiate bio-instability from impaired
      catalysis by the leucine substitution, we purified wild-type and L135-hGALT
      proteins to homogeneity and analyzed identical amounts of enzyme protein. We
      found that the apparent Vmax of the purified L135-hGALT protein was significantly
      reduced from 80 +/- 5.9 to 5.8 +/- 1.8 micromol glucose 1-phosphate
      released/min/mg hGALT protein with no increase in KM for galactose 1-phosphate
      for the second displacement. The first displacement reaction, although three
      orders of magnitude slower, was similar between the wild type and L135-hGALT. We
      conclude that a hydroxyl group on amino acid 135 is required for the catalysis of
      uridyl transfer from UDP-glucose to UDP-galactose in the presence of galactose 1
      phosphate, and plays a role in the bio-stability of hGALT.

PMID- 11592824
TI  - Characterization of a murine high-affinity thiamine transporter, Slc19a2.
AB  - Thiamine-responsive megaloblastic anemia with deafness and diabetes (TRMA) is a
      rare autosomal recessive disorder of thiamine transport. Previous studies have
      demonstrated that the disease is caused by mutations in the SLC19A2 gene encoding
      a high-affinity thiamine transporter. We hypothesize that thiamine transport,
      mediated by SLC19A2, plays a role in the development and or maintenance of
      several organ systems, in particular the erythropoietic, auditory, and glucose
      homeostasis systems. To investigate the transporter further, we cloned the murine
      Slc19a2 locus and characterized the resulting protein. Murine Slc19a2 is a 498
      amino acid protein, with 12 predicted transmembrane domains. The gene spans
      approximately 13kb with 6 exons, structurally identical to that of the human
      homolog. We localized the Slc19a2 gene to mouse chromosome 1, a region syntenic
      to human chromosome 1q23 that contains the TRMA locus. Transient expression of
      Slc19a2 in HEK293T cells resulted in specific uptake of [3H] thiamine, confirming
      a thiamine transporter function. Western blot analysis of mouse tissues reveals a
      wide distribution of Slc19a2 protein. Immunohistochemistry studies indicate that
      Slc19a2 is expressed on the cell surface and intracellularly, and is specifically
      localized to a subpopulation of cells in cochlea, small intestine, and pancreas.

PMID- 11592827
TI  - Lentiviral vectors approach the clinic but fall back: National Institutes of
      Health Recombinant DNA Advisory Committee review of a first clinical protocol for
      use of a lentiviral vector.

PMID- 11592825
TI  - Effect of triplet repeat expansion on chromatin structure and expression of DMPK
      and neighboring genes, SIX5 and DMWD, in myotonic dystrophy.
AB  - Myotonic dystrophy (DM), an autosomal dominant neuromuscular disease, is
      associated with expansion of a polymorphic (CTG)n repeat in the 3'-untranslated
      region of the DM protein kinase (DMPK) gene. The repeat expansion results in
      decreased levels of DMPK mRNA and protein, but the mechanism for this decreased
      expression is unknown. Loss of a nuclease-hypersensitive site in the region of
      the repeat expansion has been observed in muscle and skin fibroblasts from DM
      patients, indicating a change in local chromatin structure. This change in
      chromatin structure has been proposed as a mechanism whereby the expression of
      DMPK and neighboring genes, sine oculis homeobox (Drosophila) homolog 5 (SIX5)
      and dystrophia myotonica-containing WD repeat motif (DMWD), might be affected. We
      have developed a polymerase chain reaction (PCR)-based method to assay the
      chromatin sensitivity of the region adjacent to the repeat expansion in somatic
      cell hybrids carrying either normal or affected DMPK alleles and show that
      hybrids carrying expanded alleles exhibit decreased sensitivity to PvuII
      digestion in this region. Semiquantitative multiplex reverse transcriptase PCR
      (RT/PCR) assays of gene expression from the chromosomes carrying the expanded
      alleles showed marked reduction of DMPK mRNA, partial inhibition of SIX5
      expression from a congenital DM chromosome, and no reduction of DMWD mRNA. Nested
      RT/PCR analysis of DMPK mRNA from somatic cell hybrids carrying the repeat
      expansions revealed that most of the DMPK transcripts expressed from the expanded
      alleles lacked exons 13 and 14, whereas full-length transcripts were expressed
      predominantly from the normal alleles. These results suggest that the CTG repeat
      expansion leads to a decrease in DMPK mRNA levels by affecting splicing at the 3'
      end of the DMPK pre-mRNA transcript.

PMID- 11592829
TI  - Stanfield Rogers: insights into virus vectors and failure of an early gene
      therapy model.

PMID- 11592830
TI  - Infection of purified nuclei by adeno-associated virus 2.
AB  - Adeno-associated virus 2 (AAV), a nonpathogenic human parvovirus, requires co
      infection with a helper virus for its optimal replication. Although AAV possesses
      a broad host range, certain cell types lack the machinery necessary for efficient
      entry into the cell and intracellular trafficking of AAV into the nucleus, where
      the viral second-strand DNA synthesis must occur before gene expression. We have
      demonstrated that in less-permissive mouse fibroblasts, the virus fails to
      transport to the nucleus due to altered endocytic processing. However, relatively
      little is known about the intracellular site of viral uncoating and transport of
      the virion across the nuclear envelope. Here, we provide evidence that AAV can
      efficiently enter intact nuclei purified from both permissive and less-permissive
      cell types. Furthermore, entry into the nucleus is time- and temperature
      dependent, but is not saturable and seems to occur independently of the nuclear
      pore complex. We also demonstrate that purified nuclei contain all of the
      machinery necessary for uncoating and viral second-strand DNA synthesis even in
      the absence of a helper virus. These studies provide new insights into the basic
      biology of AAV and may also have implications for the optimal use of AAV vectors
      in human gene therapy.

PMID- 11592831
TI  - Noninvasive optical imaging of firefly luciferase reporter gene expression in
      skeletal muscles of living mice.
AB  - The ability to monitor reporter gene expression noninvasively offers significant
      advantages over current techniques such as postmortem tissue staining or enzyme
      activity assays. Here we demonstrate a novel method of repetitively tracking in
      vivo gene expression of firefly luciferase (FL) in skeletal muscles of mice using
      a cooled charged coupled device (CCD) camera. We first show that the cooled CCD
      camera provides consistent and reproducible results within +/-8% standard
      deviation from mean values, and a detection sensitivity (range tested: 1 x 10(4) 
      1 x 10(9) plaque form-ing units (pfu)) of 1 x 10(6) pfu of E1-deleted adenovirus
      expressing FL driven by a cytomegalovirus promoter (Ad-CMV-FL). The duration and
      magnitude of adenoviral mediated (1 x 10(9) pfu) FL gene expression were then
      followed over time. FL gene expression in immunocompetent Swiss Webster mice
      peaks within the first 48 hours, falls by 98% after 20 days, and persists for
      >150 days. In contrast, FL activity in nude mice remains elevated for >110 days.
      Finally, transduced Swiss Webster and nude mice were sacrificed to show that the
      in vivo CCD signals correlate well with in vitro luciferase enzyme assays
      (r(2)=0.91 and 0.96, respectively). Our findings demonstrate the ability of the
      cooled CCD camera to sensitively and noninvasively track the location, magnitude,
      and persistence of FL gene expression. Monitoring of gene therapy studies in
      small animals may be aided considerably with further extensions of this
      technique.

PMID- 11592832
TI  - Adenovirus-mediated gene therapy for corneal clouding in mice with
      mucopolysaccharidosis type VII.
AB  - Recent advances in systemic treatments for mucopolysaccharidosis have led to
      therapies that improve the multiple somatic features of this disease, but the
      therapeutic effect on ocular manifestations such as corneal clouding is not
      satisfactory. Here, we administered an adenovirus expressing human beta
      glucuronidase (AxCAhGUS) into the anterior chamber or intrastromal region of the
      cornea in mice with mucopolysaccharidosis type VII (B6/MPSVII), and successfully
      treated corneal clouding of MPSVII. When we injected AxCAhGUS into the anterior
      chamber of the eyes, cells expressing beta-glucuronidase (GUSB) were located
      mainly in the trabecular meshwork as well as in all corneal regions, and
      subsequent pathological corrections in the cornea were achieved. Widespread
      transgene expression was also observed when we administered AxCAhGUS inside the
      cornea after lamellar keratotomy, and rapid elimination of the lysosomal storage
      in the corneal keratocytes occurred. Furthermore, intrastromal vector
      administration did not generate significant levels of anti-adenovirus
      neutralizing antibodies, and secondary vector administration was effective. Based
      on these observations, we conclude that it is worth developing a treatment
      strategy for corneal clouding in mucopolysaccharidosis based on direct
      intraocular administration of adenoviral vectors.

PMID- 11592833
TI  - Combined administration of plasmids encoding IL-4 and IL-10 prevents the
      development of autoimmune diabetes in nonobese diabetic mice.
AB  - Studies of animals with spontaneous autoimmune diabetes have revealed that
      autoreactive T cells that mediate islet beta-cell destruction belong to the Th1
      subset (producing IL-2 and IFN-gamma), whereas regulatory T cells are Th2 type
      (producing IL-4 and IL-10). Here, we evaluate the effect of combined delivery of
      plasmid DNA encoding IL-4 and IL-10 using a degradable, cationic polymeric
      carrier, poly[gamma-(4-aminobutyl)-L-glycolic acid] (PAGA), in nonobese diabetic
      (NOD) mice. In the liver of NOD mice, we detected mouse Il4 and Il10 mRNA 5 days
      after intravenous injection of both PAGA-Il4 and PAGA-Il10 plasmid complexes. We
      found that 6 weeks after injection, 75% of observed islets were intact compared
      with less than 3% in the control group. Furthermore, in the treatment group, only
      5% of the islets were severely infiltrated by the lymphocytes compared with over
      30% in the control group. We measured glucose levels weekly up to the age of 32
      weeks, revealing that co-injection of PAGA-Il4 and PAGA-Il10 plasmids prevented
      the development of diabetes in 75% of the treated animals. Thus, combined
      administration of mouse Il4 and Il10 plasmids prevents the development of
      autoimmune diabetes in NOD mice.

PMID- 11592834
TI  - Slow accumulation of plasmid in muscle cells: supporting evidence for a mechanism
      of DNA uptake by receptor-mediated endocytosis.
AB  - Intramuscular plasmid DNA injection results in long-term but low and variable
      expression of the injected genes. Optimization is difficult because the mechanism
      of naked DNA uptake by the cells in vivo is not yet determined. Here we used
      injections of plasmid DNA encoding luciferase to further characterize this
      mechanism. We analyzed the kinetics of naked DNA uptake by means of DNase I or
      heparin injections, using the level of luciferase expression as the indicator of
      DNA uptake. We demonstrated that in vivo heparin inhibits DNA uptake without
      affecting the expression of DNA internalized by means of electric pulses.
      Inhibition by heparin is dose dependent and compatible with the competition for
      the binding to a receptor. As shown also with DNase I, DNA uptake by muscle cells
      is slow: a progressive accumulation of the DNA in the myofibers can be found for
      at least 4 hours after naked DNA injection. Physical presence of DNA molecules
      during the uptake period, but not later, was confirmed by the facilitation of DNA
      uptake with appropriate electric pulses. Therefore, uptake proceeds for the
      entire time during which intact DNA is present in the extracellular compartment.
      Our results support evidence for a DNA uptake mechanism based on receptor
      mediated endocytosis.

PMID- 11592835
TI  - Functional effect of adeno-associated virus mediated gene transfer of aromatic L
      amino acid decarboxylase into the striatum of 6-OHDA-lesioned rats.
AB  - In animal models of Parkinson's disease, gene transfer of aromatic L-amino acid
      decarboxylase (AADC) leads to an increase in the capacity of the striatum to
      decarboxylate exogenous L-DOPA. However, the functional effects of enhanced L
      DOPA to dopamine conversion have not been explored. Here, we show that following
      adeno-associated virus (AAV)-AADC transduction, the transgenic AADC is able to
      decarboxylate exogenous L-DOPA more efficiently so that a dose of L-DOPA
      ineffective before gene transfer elicits a motor asymmetry (rotational behavior)
      following gene transfer. Furthermore, rotation scores showed a strong correlation
      with AADC activity in the lesioned striatum, thus allowing for behavioral
      screening of successful gene transfer in the brain. In animals receiving AAV2
      AADC, dopamine production was restored to 50% of normal levels 12 weeks after the
      infusion. Microdialysis experiments demonstrated an in vivo enhanced conversion
      of L-DOPA to dopamine, but no storage capacity as dopamine was released to the
      extracellular space in a continuous, nonregulated fashion. In addition to the
      potential clinical benefit of improving decarboxylation efficiency in Parkinson's
      disease, our approach may be relevant for the treatment of AADC deficiency, a
      rare, autosomal recessive disorder causing a severe movement disorder and
      progressive cognitive impairment.

PMID- 11592836
TI  - Gene therapy of a mouse model of protoporphyria with a self-inactivating
      erythroid-specific lentiviral vector without preselection.
AB  - Successful treatment of blood disorders by gene therapy has several
      complications, one of which is the frequent lack of selective advantage of
      genetically corrected cells. Erythropoietic protoporphyria (EPP), caused by a
      ferrochelatase deficiency, is a good model of hematological genetic disorders
      with a lack of spontaneous in vivo selection. This disease is characterized by
      accumulation of protoporphyrin in red blood cells, bone marrow, and other organs,
      resulting in severe skin photosensitivity. Here we develop a self-inactivating
      lentiviral vector containing human ferrochelatase cDNA driven by the human
      ankyrin-1/beta-globin HS-40 chimeric erythroid promoter/enhancer. We collected
      bone marrow cells from EPP male donor mice for lentiviral transduction and
      injected them into lethally irradiated female EPP recipient mice. We observed a
      high transduction efficiency of hematopoietic stem cells resulting in effective
      gene therapy of primary and secondary recipient EPP mice without any selectable
      system. Skin photosensitivity was corrected for all secondary engrafted mice and
      was associated with specific ferrochelatase expression in the erythroid lineage.
      An erythroid-specific expression was sufficient to reverse most of the clinical
      and biological manifestations of the disease. This improvement in the efficiency
      of gene transfer with lentiviruses may contribute to the development of
      successful clinical protocols for erythropoietic diseases.

PMID- 11592837
TI  - Repression of GAD autoantigen expression in pancreas beta-Cells by delivery of
      antisense plasmid/PEG-g-PLL complex.
AB  - It was previously reported that silencing of the expression of glutamic acid
      decarboxylase (GAD) in transgenic nonobese diabetic (NOD) mice completely
      protected islet beta-cells against development of diabetes. This suggests that
      the repression of GAD autoantigen by somatic gene delivery can prevent autoimmune
      destruction of pancreatic beta-cells. To repress GAD expression in islet beta
      cells, we delivered an antisense GAD mRNA expression plasmid (pRIP-AS-GAD) using
      poly(ethylene glycol)-grafted poly-L-lysine (PEG-g-PLL) as a gene carrier. In a
      gel retardation assay, the pRIP-AS-GAD/PEG-g-PLL complex was completely retarded
      above a weight ratio of 1:1.5 (plasmid: PEG-g-PLL). PEG-g-PLL protected the
      plasmid DNA from DNase I for more than 60 minutes. In a reporter gene
      transfection assay, PEG-g-PLL showed the highest transfection efficiency at a
      weight ratio of 1:3. We also transfected pRIP-AS-GAD/PEG-g-PLL complex into a GAD
      producing mouse insulinoma (MIN6) cell line. The antisense mRNA was expressed
      specifically in beta-cells and expression was dependent on glucose level. The
      repression of GAD after transfection of pRIP-AS-GAD was confirmed by immunoblot
      assay. In addition, in vivo expression of antisense RNA in pancreas was confirmed
      by RT-PCR after intravenous injection of the complex into mice. Therefore, our
      study revealed that the pRIP-AS-GAD/PEG-g-PLL system is applicable for the
      repression of GAD autoantigen expression.

PMID- 11592838
TI  - Antitumor activity of cationic lipid complexed with immunostimulatory DNA.
AB  - We previously reported that treatment of intraperitoneal tumors with complexes of
      cationic lipid and noncoding plasmid DNA leads to the development of a specific,
      cytotoxic T-cell response correlating with the rejection of established tumor
      cells as well as subsequent tumor re-challenge. Here, focusing on an
      intraperitoneal AB12 mesothelioma model, we show that the anticancer effects of
      the lipid:DNA complex are associated with DNA containing immunostimulatory CpG
      motifs. Complexes prepared with cationic lipid and bacterial plasmid DNA,
      Escherichia coli genomic DNA fragments, or synthetic immunostimulatory CpG
      oligodeoxynucleotides provided a substantial survival benefit, whereas eukaryotic
      DNA and methylated bacterial DNA had little or no therapeutic activity.
      Alternative inflammatory stimuli such as thioglycolate, poly(I:C), and incomplete
      or complete Freund's adjuvant failed to reproduce the antitumor activity obtained
      with the lipid:DNA complex. The innate immune response triggered by lipid:DNA
      complexes led to the development of a systemic immune response against tumor
      cells that allowed animals to reject tumors not only at the intraperitoneal
      treatment site, but also at a distal subcutaneous site. These data demonstrate
      that immunostimulatory DNA complexed with cationic lipid is a potent inducer of
      innate and adaptive immune responses against tumor cells and represents a
      potentially useful tool in the immunotherapy of cancers for which tumor
      associated antigens have not been identified.

PMID- 11592839
TI  - Human and mouse IFN-beta gene therapy exhibits different anti-tumor mechanisms in
      mouse models.
AB  - Previously, we suggested that local human interferon-beta (IFN-beta) gene therapy
      with replication-defective adenoviral vectors can be an effective cancer
      treatment. Clinical trials to treat cancers with adenovirus expressing the human
      IFN-beta gene (IFNB1) has been planned. As a continued effort to explore the
      mechanisms of action of human IFN-beta gene therapy that can occur in the
      clinical setting, we tested mouse IFN-beta gene therapy in human xenograft tumors
      in both ex vivo and in vivo models. Delivery of the mouse IFN-beta gene (Ifnb)
      caused tumor inhibition; this effect was dependent on the indirect anti-tumor
      activities of IFN-beta, notably a stimulation of natural killer cells. IFN-beta
      does not show cross-species activity in its anti-proliferative effect and mouse
      IFN-beta does not cause as significant an anti-proliferative effect on mouse
      tumor cells as human IFN-beta causes on human tumor cells. Therefore, we believe
      that mouse models using either human IFN-beta or mouse IFN-beta gene transfer do
      not capture all aspects of the action of adenovirus-mediated human IFN-beta gene
      therapy that may be present in the clinical setting. Due to its multiple
      mechanisms of action, human IFN-beta gene therapy may be effective in treating
      human cancers that are either sensitive or resistant to the direct anti
      proliferative effect of IFN-beta.

PMID- 11592840
TI  - High-level, beta-catenin/TCF-dependent transgene expression in secondary
      colorectal cancer tissue.
AB  - There is an urgent need for improved therapies for inoperable metastatic colon
      cancer. Gene-directed enzyme prodrug therapy (GDEPT) using adenovirus vectors
      works well in preclinical models of this disease, but successful clinical
      application is hampered by an inability to construct vectors that express at high
      levels in infected tumor cells but not in infected normal cells. Constitutive
      activation of beta-catenin-dependent gene expression is almost certainly a key
      causative event in the genesis of colon and some other cancers. Here we have
      exploited this oncogenic defect to design a synthetic promoter, CTP1, that, in
      contrast to currently available tumor-selective promoters, is both highly active
      in cancer cells and highly cancer-cell-specific. CTP1 directs high-level beta
      galactosidase expression in freshly isolated biopsies of secondary colon cancer,
      but is not detectably active in associated normal liver tissue. We also
      demonstrate that CTP1 can direct high-level, tumor-specific therapeutic gene
      expression in vivo. Intratumoral injection of an adenovirus vector encoding
      Escherichia coli nitroreductase driven by CTP1 efficiently sensitized SW480
      xenografts to the prodrug CB1954, whereas systemic vector and prodrug
      administration produced no apparent signs of toxicity. CTP1 may form the basis
      for effective, targeted gene therapy of metastatic colon cancer and other tumors
      with deregulated beta-catenin/T cell factor.

PMID- 11592841
TI  - A single-step affinity column for purification of serotype-5 based adeno
      associated viral vectors.
AB  - Here we describe a single-step affinity column for purification of vectors based
      on adeno-associated virus type 5 (AAV5). A sialic-acid-rich protein called mucin
      was covalently attached to Sepharose and was found to bind AAV5 vectors. Elution
      with high salt efficiently recovered highly active vectors of greater purity than
      what is achieved with CsCl(2) sedimentation.

PMID- 11592842
TI  - Multigene lentiviral vectors based on differential splicing and translational
      control.
AB  - Lentiviral vectors, so far, have been optimized for the expression of a single
      open reading frame. Certain practical applications of gene therapy will, however,
      require expression of multiple genes. The goal of this study was to explore the
      feasibility of directing expression of two marker genes from a lentiviral vector.
      We designed two types of multigene lentiviral vectors. First, we used a strategy
      based on the natural splicing signals of HIV-1, by which multiple mRNAs are
      generated from a single transcriptional unit. A second strategy was construction
      of a polycistronic mRNA using a translational cis-acting element, the
      encephalomyocarditis virus internal ribosome entry site (IRES). Our studies show
      that the inclusion of multiple genes in lentiviral vectors does not result in
      reduction in virus titers or in the loss of ability to infect nondividing cells.
      We introduced mutations in tat and/or rev to test whether splicing modulates the
      relative levels of expression of reporter genes. We also developed a truncated
      version of tat, which is devoid of the apoptosis-associated domain. Inclusion of
      this tat mutant in a lentiviral vector resulted in the generation of virus with
      titers similar to those of lentivirus vectors expressing wild-type tat.

PMID- 11592843
TI  - Expanding AAV packaging capacity with trans-splicing or overlapping vectors: a
      quantitative comparison.
AB  - Recombinant adeno-associated (rAAV) viral vectors hold great therapeutic
      potential for human diseases. However, a relatively small packaging capacity
      (less than 5 kb) has limited the application of rAAV for certain diseases such as
      cystic fibrosis and Duchenne muscular dystrophy. Here we compared two
      mechanistically distinct approaches to overcome packaging restraints with rAAV
      vectors. The trans-splicing approach reconstitutes gene expression from two
      independent rAAV vectors, each encoding unique, nonoverlapping halves of a
      transgene. This process requires intermolecular concatamerization and subsequent
      splicing between independent vectors. A distinct overlapping vector approach uses
      homologous recombination between overlapping regions in two independent vectors.
      Using the beta-galactosidase gene as template, trans-splicing approaches were
      threefold (in primary fibroblasts) and 12-fold (in muscle tissue) more effective
      in generating full-length transgene products than the overlapping vector
      approach. Nevertheless, the efficiency of trans-splicing remained moderate at
      approximately 4.3% (for muscle) and 7% (for fibroblasts) of that seen with a
      single vector encoding the full-length transgene. The efficiency of trans
      splicing was augmented 1185-fold by adenoviral E4, but not E2a, gene products.
      This augmentation was much less pronounced with the overlapping vectoring
      approach (12-fold). Trans-splicing and overlapping vector approaches are two
      viable alternatives to expand rAAV packaging capacity.

PMID- 11592844
TI  - Dendritic spine hypoplasticity and downregulation of reelin and GABAergic tone in
      schizophrenia vulnerability.
AB  - In this review, we will first present a brief overview of the current
      understanding of: (a) the biology of reelin; (b) the putative reelin signaling
      pathways via integrin receptor stimulation; (c) the cytosolic adapter protein
      DAB1, which appears to be operative in the transduction of reelin's pleiotropic
      actions in embryonic, adolescent, and adult brain; (d) the regulation of
      GABAergic function, including some aspects of GABAergic system development; and
      (e) dendritic spine function and its role in the regulation of synaptic
      plasticity. We argue that a downregulation of reelin expression occurring in
      prefrontal cortex and in every brain structure of schizophrenia patients so far
      studied may be associated with a decrease in dendritic spine expression that in
      turn may provide an important reduction of cortical function as documented by the
      downregulation of glutamic acid decarboxylase67 (GAD67) expression, which might
      be secondary to a reduction of GABAergic axon terminals. This hypothesis is
      supported by a genetic mouse model of reelin haploinsufficiency that replicates
      the above-described dendritic and presynaptic GABAergic defects documented in
      schizophrenia brains.

PMID- 11592845
TI  - Prion diseases: what is the neurotoxic molecule?
AB  - A great deal of effort has been devoted during the past 20 years to defining the
      chemical nature of prions, the infectious agents responsible for transmissible
      spongiform encephalopathies. In contrast, much less attention has been paid to
      elucidating how prions actually damage the central nervous system. Although it is
      commonly assumed that PrP(Sc), the protein constituent of infectious prions, is
      the primary culprit, increasing evidence indicates that this may not be the case.
      Several alternative molecular forms of PrP are reasonable candidates for the
      neurotoxic species in prion diseases, although it is still too early to tell
      whether these or other ones will turn out to be the true instigating factors. The
      cellular pathways activated by neurotoxic forms of PrP that ultimately result in
      neuronal death are also being investigated, and several possible mechanisms have
      been uncovered, including the operation of quality control processes in the
      endoplasmic reticulum. Elucidating the distinction between the infectious and
      neurotoxic forms of PrP has important implications for designing therapy of prion
      diseases, as well as for understanding pathogenic mechanisms operative in other
      neurodegenerative disorders and the role of prion-like states in biology.

PMID- 11592846
TI  - GDNF protects against aluminum-induced apoptosis in rabbits by upregulating Bcl-2
      and Bcl-XL and inhibiting mitochondrial Bax translocation.
AB  - Direct (intracisternal) injection of aluminum complexes into rabbit brain results
      in a number of similarities with the neuropathological and biochemical changes
      observed in Alzheimer's disease and provides the opportunity to assess early
      events in neurodegeneration. This mode of administration induces cytochrome c
      release from mitochondria, a decrease in Bcl-2 in both mitochondria and
      endoplasmic reticulum, Bax translocation into mitochondria, activation of caspase
      3, and DNA fragmentation. Coadministration of glial cell neuronal-derived factor
      (GDNF) inhibits these Bcl-2 and Bax changes, upregulates Bcl-XL, and abolishes
      the caspase-3 activity. Furthermore, treatment with GDNF dramatically inhibits
      apoptosis, as assessed by the TUNEL technique for detecting DNA damage. Treatment
      with GDNF may represent a therapeutic strategy to reverse the neuronal death
      associated with Alzheimer's disease and may exert its effect on apoptosis
      regulatory proteins.

PMID- 11592848
TI  - Expression pattern of the Rett syndrome gene MeCP2 in primate prefrontal cortex.
AB  - Dysfunction of the prefrontal cortex may contribute to the autistic features and
      mental retardation of Rett syndrome, a neuropsychiatric condition caused by
      mutations of the gene encoding methyl-CpG-binding protein 2 (MeCP2). Because
      nothing is known about the expression of MeCP2 and other chromatin-associated
      factors in primate brain, we studied in monkey prefrontal cortex and murine
      cerebral cortex expression patterns of MeCP2 and of macrohistone H2A (MacroH2A),
      which like MeCP2 is associated with transcriptionally silent chromatin. In both
      species, MeCP2 and MacroH2A appeared to be ubiquitously expressed by cortical
      neurons, including projection neurons and GABAergic interneurons. In the adult
      monkey, MeCP2 expression was robust throughout all layers of the prefrontal
      cortex but it was limited in fetal monkeys at embryonic day 110 to the deeper
      cortical layers and the subplate. These results suggest that MeCP2 may be
      important for neuronal maintenance in the developing and in the mature primate
      prefrontal cortex, consistent with the previously reported phenotype of MeCP2
      null mutant mice.

PMID- 11592847
TI  - Attenuation of Zn2+ neurotoxicity by aspirin: role of N-type Ca2+ channel and the
      carboxyl acid group.
AB  - Synaptically released Zn2+ ions enter into neurons primarily through voltage
      gated Ca2+ channels (VGCC) or N-methyl-d-aspartate (NMDA) receptors, which can
      mediate pathological neuronal death. We studied the possibility (and underlying
      mechanisms) that aspirin, known to prevent NMDA neurotoxicity, would also
      attenuate Zn2+ neurotoxicity. Administration of 3 to 10 mM aspirin, in cortical
      cell cultures, attenuated the evolution of neuronal death following exposure to
      300 microM Zn2+ for 30 min. This neuroprotective effect of aspirin was
      attributable to the prevention of Zn2+ ion entry. Aspirin interfered with inward
      currents and an increase in [Ca2+]i through VGCC and selective binding of omega
      conotoxin, sensitive to N-type Ca2+ channel. The omega-conotoxins GVIA or MVIIC,
      the selective inhibitors of N-type Ca2+ channels, attenuated Zn2+ neurotoxicity.
      Aspirin derivatives lacking the carboxyl acid group did not reduce Zn2+
      neurotoxicity. The present findings suggest that aspirin prevents Zn2+-mediated
      neuronal death by interfering with VGCC, and its action specifically requires the
      carboxyl acid group.

PMID- 11592849
TI  - Oxidation of Abeta and plaque biogenesis in Alzheimer's disease and Down
      syndrome.
AB  - The processes involved with beta-amyloid (Abeta) degradation and clearance in
      human brain are not well understood. We hypothesized that the distribution of
      oxidatively modified Abeta, as determined by an affinity-purified antibody in the
      entorhinal and frontal cortices of Alzheimer's disease (AD), Down syndrome (DS),
      nondemented elderly control cases, and canine brain, would provide insight into
      the mechanisms of Abeta accumulation. Based upon plaque counts, oxidized Abeta
      was present within 46-48% of diffuse and primitive plaques and 98% of cored
      plaques. Dense punctate deposits of oxidized Abeta were distributed throughout
      the neuropil in AD and DS brains but were also present within controls with mild
      neuropathology and isolated cognitive impairments. Confocal studies indicate that
      punctate oxidized Abeta deposits were within activated microglia. Oxidatively
      modified Abeta may reflect the efforts of microglial cells to take up and degrade
      Abeta. Oxidative modification of Abeta may be an early event in Abeta
      pathogenesis and may be important for plaque biogenesis.

PMID- 11592850
TI  - Impaired glutamate uptake in the R6 Huntington's disease transgenic mice.
AB  - Huntington's disease (HD) is a late-onset neurodegenerative disease for which the
      mutation is CAG/polyglutamine repeat expansion. The R6 mouse lines expressing the
      HD mutation develop a movement disorder that is preceded by the formation of
      neuronal polyglutamine aggregates. The phenotype is likely caused by a widespread
      neuronal dysfunction, whereas neuronal cell death occurs late and is very
      selective. We show that a decreased mRNA level of the major astroglial glutamate
      transporter (GLT1) in the striatum and cortex of these mice is accompanied by a
      concomitant decrease in glutamate uptake. In contrast, the expression of the
      glutamate transporters, GLAST and EAAC1, remain unchanged. The mRNA level of the
      astroglial enzyme glutamine synthetase is also decreased. These changes in
      expression occur prior to any evidence of neurodegeneration and suggest that a
      defect in astrocytic glutamate uptake may contribute to the phenotype and
      neuronal cell death in HD.

PMID- 11592851
TI  - A murine dopamine neuron-specific cDNA library and microarray: increased COX1
      expression during methamphetamine neurotoxicity.
AB  - Due to brain tissue heterogeneity, the molecular genetic profile of any
      neurotransmitter-specific neuronal subtype is unknown. The purpose of this study
      was to purify a population of dopamine neurons, construct a cDNA library, and
      generate an initial gene expression profile and a microarray representative of
      dopamine neuron transcripts. Ventral mesencephalic dopamine neurons were purified
      by fluorescent-activated cell sorting from embryonic day 13.5 transgenic mice
      harboring a 4.5-kb rat tyrosine hydroxylase promoter-lacZ fusion. Nine-hundred
      sixty dopamine neuron cDNA clones were sequenced and arrayed for use in studies
      of gene expression changes during methamphetamine neurotoxicity. A neurotoxic
      dose of methamphetamine produced a greater than twofold up-regulation of the
      mitochondrial cytochrome c oxidase polypeptide I transcript from adult mouse
      substantia nigra at 12 h posttreatment. This is the first work to describe a gene
      expression profile for a neuronal subtype and to identify gene expression changes
      during methamphetamine neurotoxicity.

PMID- 11592852
TI  - Expression and activation of matrix metalloproteinase-2 and -9 in rat brain after
      transient focal cerebral ischemia.
AB  - Matrix metalloproteinases (MMPs) degrade the extracellular matrix and carry out
      key functions during development and after injury. By means of zymography,
      Western blot and immunohistochemistry, we studied MMP-2 (gelatinase A) and MMP-9
      (gelatinase B) in rat brain after focal cerebral ischemia. The control rat brain
      showed constitutive MMP-2 and, to a lesser extent, MMP-9, which were mainly
      present as prozymogens. MMP-2 protein was located in the cell body of neurons,
      glia, and endothelium, whereas MMP-9 was associated to neurons and myelinated
      fibre tracts. Ischemia greatly increased MMP activation in two temporal waves, in
      the first one, MMP-9 protein was induced from 4 h to 4 days, and also a small and
      short-lasting increase in MMP-2 was detected at 4 h. The second wave showed a
      massive increase in MMP-2 protein expression and activation by day 4, which was
      compatible with abundant MMP-2 in reactive microglia/macrophages. Our results are
      compatible with progressive induction of MMP-9 proform, likely in neurons,
      shortly after ischemia. For MMP-2, the results suggest a discrete production
      immediately after reperfusion, while a very enhanced expression and activation of
      MMP-2 attributable to microglia/macrophages occurs on day 4, and it might
      contribute to the phagocytic action of these reactive cells.

PMID- 11592853
TI  - Gene expression profiling in postmortem Rett Syndrome brain: differential gene
      expression and patient classification.
AB  - The identification of mutations in the transcriptional repressor methyl-CpG
      binding protein 2 (MECP2) gene in Rett Syndrome (RTT) suggests that an
      inappropriate release of transcriptional silencing may give rise to RTT
      neuropathology. Despite this progress, the molecular basis of RTT
      neuropathogenesis remains unclear. Using multiple cDNA microarray technologies,
      subtractive hybridization, and conventional biochemistry, we generated
      comprehensive gene expression profiles of postmortem brain tissue from RTT
      patients and matched controls. Many glial transcripts involved in known
      neuropathological mechanisms were found to have increased expression in RTT
      brain, while decreases were observed in the expression of multiple neuron
      specific mRNAs. Dramatic and consistent decreases in transcripts encoding
      presynaptic markers indicated a specific deficit in presynaptic development.
      Employing multiple clustering algorithms, it was possible to accurately segregate
      RTT from control brain tissue samples based solely on gene expression profile.
      Although previously achieved in cancers, our results constitute the first report
      of human disease classification using gene expression profiling in a complex
      tissue source such as brain.

PMID- 11592854
TI  - Potential role of endogenous brain-derived neurotrophic factor in long-term
      neuronal reorganization of the superior colliculus after bilateral visual
      deprivation.
AB  - The role of the brain-derived neurotrophic factor (BDNF), the BDNF receptor
      (TrkB), and the glutamic acid decarboxylase (GAD67) after neonatal, bilateral
      nerve deafferentiation during postnatal development was investigated in the rat
      superior colliculus (SC). BDNF and GAD67 mRNA expression were significantly
      increased in optic (Op) and intermediate gray (InG) layers at 5, 8, 15, and 21
      days after birth, but not in adult animals. However, TrkB mRNA expression was not
      modified at any time tested. At 15 days, where changes in BDNF and GAD67 mRNAs
      were more evident, an upregulation of the NMDAR(1A) mRNA glutamate receptor in
      the Op and InG, a modification in the pattern of synaptic zinc in the superficial
      layers of SC, and an increased synaptophysin immunoreactivity in the Op was
      found. This indicates the existence of a synergic mechanism between BDNF and NMDA
      to determine refinement of connections after the loss of visual input in SC.

PMID- 11592855
TI  - Prominent stress response of Purkinje cells in Creutzfeldt-Jakob disease.
AB  - To examine the role of stress-related 70-kDa heat shock proteins (Hsp-s) in
      Creutzfeldt-Jakob disease (CJD), we performed immunocytochemistry to detect Hsp
      72 and Hsp-73, together with the abnormal (PrP(Sc)) and the presumed cellular
      form (PrP(C)) of the prion protein, and TUNEL method to measure cellular
      vulnerability in different brain regions in CJD and control cases. While Hsp-73
      showed uniform distribution in all the examined samples, an increase in the
      number of Purkinje cells with prominent accumulation of Hsp-72 in the CJD group
      was observed. These neurons also showed intense PrP(C) staining, but TUNEL
      positive nuclei were only detected in the granular (Hsp-72-negative) cell layer.
      Fewer cells of the inferior olivary nucleus were immunoreactive for Hsp-72 in CJD
      than in control cases, and regions showing severe spongiform change and gliosis
      exhibited fewer Hsp-72-immunoreactive neurons. Our results indicate that
      accumulation of the inducible Hsp-72 in certain cell types may be part of a
      cytoprotective mechanism, which includes preservation of proteins like PrP(C).

PMID- 11592856
TI  - A cholesterol-lowering drug reduces beta-amyloid pathology in a transgenic mouse
      model of Alzheimer's disease.
AB  - Clinical, epidemiological, and laboratory studies suggest that cholesterol may
      play a role in the pathogenesis of Alzheimer's disease (AD). Transgenic mice
      exhibiting an Alzheimer's beta-amyloid phenotype were treated with the
      cholesterol-lowering drug BM15.766 and tested for modulation of beta-amyloid
      levels. BM15.766 treatment reduced plasma cholesterol, brain Abeta peptides, and
      beta-amyloid load by greater than twofold. A strong, positive correlation between
      the amount of plasma cholesterol and Abeta was observed. Furthermore, drug
      treatment reduced the amyloidogenic processing of the amyloid precursor protein,
      suggesting alterations in processing in response to cholesterol modulation. This
      study demonstrates that hypocholesterolemia is associated with reduced Abeta
      accumulation suggesting that lowering cholesterol by pharmacological means may be
      an effective approach for reducing the risk of developing AD.

PMID- 11592857
TI  - The neuronal calcium sensor protein VILIP-1 is associated with amyloid plaques
      and extracellular tangles in Alzheimer's disease and promotes cell death and tau
      phosphorylation in vitro: a link between calcium sensors and Alzheimer's disease?
AB  - To investigate whether the observed association of intracellular neuronal calcium
      sensor (NCS) proteins with amyloid plaques and neurofibrillar tangles in
      Alzheimer brains is linked to a possible neuroprotective or neurotoxic activity
      of the protein, we performed cytotoxicity tests in PC12 cells transfected with
      the calcium sensor protein VILIP-1 (visinin-like protein) and the calcium buffer
      protein calbindin-D28K. Whereas VILIP-1 expression enhanced the neurotoxic effect
      of ionomycin already at low ionophore concentrations, calbindin-D28K protected
      against ionomycin-induced cytotoxicity only at high ionomycin and therefore
      calcium concentrations. However, in double-transfected cells calbindin-D28K
      rescued VILIP-1-mediated cytotoxicity at low ionomycin concentrations. Since
      VILIP-1 was found to be associated with fibrillar tangles in Alzheimer brains, we
      tested whether VILIP-1 has an influence on tau hyperphosphorylation. VILIP-1
      expression enhanced hyperphosphorylation of tau protein compared to
      nontransfected or calbindin-D28K-transfected cells. These results raise the
      possibility that the observed reduction in VILIP-1-expressing cells may indicate
      a selective vulnerability of these neurons and that the calcium sensor protein is
      involved in the pathophysiology of Alzheimer's disease. The calcium sensor
      protein may influence tau phosphorylation and have a role in calcium-mediated
      neurotoxicity opposed to the previously discovered protective effect of calcium
      buffer proteins.

PMID- 11592858
TI  - New patterns of intracortical projections after focal cortical stroke.
AB  - Cortical strokes alter functional maps but associated changes in connections have
      not been documented. The neuroanatomical tracer biotinylated dextran amine (BDA)
      was injected into cortex bordering infarcts 3 weeks after focal strokes in rat
      whisker barrel (somatosensory) cortex. The mirror locus in the opposite
      hemisphere was injected as a control. After 1 week of survival, brains were
      processed for cytochrome oxidase (CO)-, Nissl-, and BDA-labeled neurons. Cortex
      bordering the infarct (peri-infarct cortex) had abnormal CO and Nissl structure.
      BDA-labeled neurons were plotted and projections were analyzed quantitatively.
      Animals with small strokes had intracortical projections, arising from peri
      infarct cortex, not seen in normal hemispheres: the overall orientation was
      statistically significantly different from and rotated 157 degrees relative to
      the controls. Compared to the controls, significantly fewer cells were labeled in
      the thalamus. Thus, after focal cortical stroke, the peri-infarct cortex is
      structurally abnormal, loses thalamic connections, and develops new horizontal
      cortical connections by axonal sprouting.

PMID- 11592859
TI  - Pharmacological control of platelet function.
AB  - Advancement in the understanding of the mechanisms of platelet activation, as
      well as the development of new techniques for studying platelet function, have
      led to the availability of new classes of platelet inhibiting drugs. Initially,
      characterization of arachidonic acid metabolism in platelets furthered an
      understanding of the utility of cyclooxygenase inhibitors, most notably aspirin.
      The discovery and characterization of platelet receptors such as the adenosine
      diphosphate (ADP) receptor and glycoprotein IIb/IIIa has been associated with the
      development of novel classes of anti-platelet drug, such as thienopyridine
      derivatives and glycoprotein IIb/IIIa receptor antagonists, respectively. Future
      development in receptor pathway inhibitors also includes glycoprotein Ib/IX as
      well as the potential use of platelet signaling pathway inhibitors.

PMID- 11592860
TI  - Fish as model in pharmacological and biological research.
AB  - Fish represent the oldest and most diverse classes of vertebrates, comprising
      around the 48% of the known member species in the subphylum Vertebrata. There are
      many scientific fields that use fish as models in research, including respiratory
      and cardiovascular research, cell culture, ecotoxicology, ageing, pharmacological
      and genetic studies.

PMID- 11592861
TI  - Flow cytometry, a useful tool for detecting the lethal effect of pentamidine on
      Leishmania viannia complex promastigote forms.
AB  - Flow cytometry (FC), combined with propidium iodide as supravital colorant, was
      used to study Leishmania(subgenus Viannia)panamensis [L (V) panamensis] complex
      strain susceptibility to meglumine antimoniate, sodium stibogluconate and
      pentamidine. Despite all drugs examined being leishmanicidal to axenic forms in
      in vitro trials (in the presence of macrophages), axenic amastigotes directly
      exposed to these drugs were highly resistant under our experimental conditions. A
      direct lethal effect on promastigotes, detectable by FC, was only obtained with
      pentamidine after in vitro treatment of both promastigotes and axenic amastigotes
      with the drugs. Pentamidine's rapid lethal effect, as detected by FC, could be
      further confirmed in short- and long-term parasite cultures after exposure to a
      drug. FC's suitability for measuring L (V) panamensis complex's promastigote
      susceptibility to pentamidine, shortly after in vitro drug exposure, might be
      useful in monitoring clinical trials with this drug and facilitating rapid
      pentamidine-resistant natural isolate identification.

PMID- 11592862
TI  - The effect of methionine-enkephalin on nitric oxide release in mice is age and
      gender related.
AB  - Gender- and age-related differences in nitric oxide (NO) release and in response
      to drugs of abuse has been reported in both humans and experimental animals. So
      far, we have demonstrated in vivo methionine-enkephalin- (MENK-) modulated NO
      release in mice. However, no data on the influence of age and gender on this
      immunomodulatory effect of MENK have been reported. In this study we examined the
      influence of age (2, 4, 8 month old mice) and gender (male and female mice) on
      MENK-induced NO release of mouse peritoneal macrophages (PEMs) of the CBA strain
      of mice. NO release was not age but was gender related in that males generally
      produced more NO than females. The effect of MENK on NO release was age
      (demonstrated only in mature 4 and 8 month old mice) and gender related in that
      it could be observed only in female mice. Apoptotic cells that paralleled the
      increase of NO in MENK-treated female mice were, however, observed also in male
      mice although MENK was in males without effect. These data provide evidence that
      some immunomodulatory properties of MENK are age and gender related which may be
      relevant to the potential use of MENK in adjuvant therapy for immunocompromised
      status.

PMID- 11592863
TI  - The antioxidant effect of rebamipide on oxygen free radical production by H.
      pylori-activated human neutrophils: in comparison with N-acetylcysteine, ascorbic
      acid and glutathione.
AB  - Helicobacter pylori(H. pylori)-activated neutrophils produce the oxygen-derived
      free radicals (OFRs) which play an important role in gastric mucosal cell damage.
      Rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid)
      is an antiulcer compound, which protects gastric mucosa against OFR-mediated
      injury. In order to investigate the effects of rebamipide on OFR production and
      to compare the antioxidant activity of rebamipide with those of three known
      antioxidants, N-acetylcysteine (AC), ascorbic acid (Vit C) and glutathione (GSH),
      the antioxidant activities were determined by luminol-dependent chemiluminescence
      (ChL) assay and pyrogallol autoxidation assay. The ChL value was markedly
      elevated immediately after the addition of H. pylori into the medium containing
      neutrophils. The antioxidant activity of 1.0 mM rebamipide was greater than that
      of 0.1 mM rebamipide in the luminol-dependent ChL assay, while in the pyrogallol
      autoxidation assay, the antioxidant activity of 1.0 mM rebamipide was similar to
      that of 0.1 mM rebamipide. Rebamipide inhibited OFR generation in the pyrogallol
      autoxidation assay, with the potency being in the order of GSH > Vit C >
      rebamipide > AC. In the luminol-dependent ChL assay, the antioxidant activity of
      rebamipide was the greatest among them. These results indicate that rebamipide is
      a potent antioxidant and scavenges OFRs produced by H. pylori effectively in
      luminol-dependent ChL assays.

PMID- 11592864
TI  - Inhibition of cholesterol biosynthesis in cultured fibroblasts by D003, a mixture
      of very long chain saturated fatty acids.
AB  - The present study was undertaken to investigate the effects of D003, a mixture of
      very long chain saturated fatty acids isolated and purified from sugar cane wax,
      on cholesterol biosynthesis in cultured fibroblasts. Cholesterol biosynthesis is
      regulated through feedback regulation of at least two sequentially acting
      enzymes, 3-hydroxy-3-methyl coenzyme A (HMG-CoA) synthase and reductase. They are
      up-regulated when sterol levels fall and down-regulated when sterol levels rise.
      The exposure of cultured fibroblasts to a lipid-depleted medium (LDM) and D003
      (0.05-50 microg ml(-1)) for 12 h inhibited, in a dose-dependent manner,
      cholesterol biosynthesis from 14C-labelled acetate (33-68%). The addition of D003
      at concentrations inhibiting cholesterol biosynthesis from labelled acetate
      significantly decreased incorporation of radioactivity from 3H2O into sterols,
      but not from 14C-mevalonate. These data indicate that D003 inhibits cholesterol
      biosynthesis by interfering with early steps of cholesterol biosynthetic pathway.
      We reasoned that D003 acts directly on HMG-CoA reductase, the main regulatory
      enzyme of cholesterol biosynthetic pathway. However, when enzyme activity was
      measured in cell extracts in the presence of various concentrations of D003 (0.5
      50 microg ml(-1)), reductase activity was not inhibited. Thus, there was no
      evidence for a competitive or non-competitive inhibition of enzyme activity by
      D003. Treatment with D003 significantly suppressed (68%) the enzyme up-regulation
      when cells were cultured in LDM, which suggests a depression of de novo synthesis
      of HMG-CoA reductase and/or a stimulation of its degradation. However, since the
      suppressive action of D003 on cholesterol biosynthesis was observed in metabolic
      conditions under which synthase up-regulation was also enhanced, we cannot rule
      out a possible effect of D003 on HMG-CoA synthase. Thus, further studies are
      needed to clarify the precise mechanism of the inhibitory effect of D003 on
      cholesterol biosynthesis.

PMID- 11592865
TI  - Effects of ischaemic stress on leukocyte activation processes in patients with
      chronic peripheral occlusive arterial disease: role of L-propionyl carnitine
      administration.
AB  - An open study was carried out to assess whether, in patients with occlusive
      peripheral arterial disease (PAD), ischaemic stress induced by maximal physical
      exercise is associated with leukocyte activation processes, and to evaluate the
      effects of L-propionyl carnitine (LPC) administration on such processes. Fifteen
      patients with occlusive PAD (stage II-A), with a mean pain-free walking distance
      (PWD) of 199 +/- 70.66 m were orally treated with 2000 mg/day LPC for 2 months.
      Serum levels of E-selectin, P-selectin, L-selectin, intercellular adhesion
      molecule-1 (ICAM-1) and vascular cell adhesion molecule-I (VCAM-1) were measured
      at rest and after the performance of a treadmill walking test (treadmill speed
      3.5 km h(-1), inclination 12%) in the untreated condition, and again after
      treatment with LPC. Significant increases of these factors were observed after
      maximal exercise compared with resting values. Such increase was significantly
      reduced after LPC treatment compared with the untreated condition. This study
      shows that ischaemia induced by maximal stress is associated with leukocyte
      activation processes, and that LPC is capable of modulating these processes. LPC,
      therefore, may have a protecting role during ischaemia.

PMID- 11592866
TI  - Spironolactone and captopril attenuates isoproterenol-induced cardiac remodelling
      in rats.
AB  - The role of renin-angiotensin-aldosterone system in cardiac remodelling was
      studied in isoproterenol-induced cardiac hypertrophy in rats. The effects of
      captopril and spironolactone were compared. Isoproterenol treatment increased
      ventricular to body weight ratio (4.6 vs 3.7) and collagen area (22.6 vs 8.2%),
      and reduced systolic (89.93 vs 107.5 mm Hg) and diastolic (59.6 vs 70.8 mm Hg)
      pressure. In these animals, captopril decreased systolic (67.4 mm Hg) and
      diastolic pressure (31.9 mm Hg), whereas spironolactone regressed systolic
      pressure to control values (101.2 mm Hg). Captopril and spironolactone prevented
      cardiac hypertrophy (4.01 and 3.95). However, only spironolactone prevented
      myocardial fibrosis (11.3%).

PMID- 11592867
TI  - Effect of vitamin C supplementation against cisplatin-induced toxicity and
      oxidative DNA damage in rats.
AB  - Antitumor agents are used as a common therapy against some kinds of cancer.
      However, as with many agents that have mammalian cell toxicity as a target,
      physiological adverse effects can occur such as nephrotoxicity and genotoxicity
      that can be induced in non-tumor cells by generating activated oxygen species,
      which attack the DNA frequently resulting in oxidative DNA damage. To diminish
      the undesirable side-effects of therapy and to reduce the levels of oxidative DNA
      damage, it is recommended for patients to ingest food supplements and vitamins
      combinations containing substantial amounts of antioxidants. In the present
      study, we investigated the effects of cisplatin and vitamin C on the renal
      toxicity and on the oxidative DNA damage. Rats were co-treated with the
      chemotherapeutic agent cisplatin (5 mg kg(-1) body weight) and dietary doses of
      vitamin C (50 and 100 mg kg(-1) body weight). Results demonstrated that depending
      on the treatment protocol, we observed alterations in parameters such as body
      weight, urinary volume and urinary creatinine, indicating some kidney toxicity.
      We also observed changes in the urinary levels of 8-OHdG, suggesting possible
      oxidative DNA damage.

PMID- 11592868
TI  - Effect of trapidil, an antiplatelet and vasodilator agent on gentamicin-induced
      nephrotoxicity in rats.
AB  - This study was carried out to evaluate the effect of trapidil, an antiplatelet
      and vasodilator drug, on the nephrotoxicity by an aminoglycoside, gentamicin, in
      rats. Forty female Wistar rats were divided into six different groups. One group
      served as a control group and the other groups were treated as follows:
      gentamicin (50 mg kg(-1) twice daily)-treated, gentamicin plus trapidil (4 or 20
      mg kg(-1) daily)-treated and only trapidil-treated (4 or 20 mg kg(-1) daily)
      groups. Serum urea, creatinine and nitrite/nitrate levels were measured.
      Moreover, histopathological as well as electron microscopic examinations were
      performed. At a lower dose (4 mg kg(-1)) trapidil did not prevent the development
      of renal tubular damage by gentamicin. However, a higher dose of trapidil (20 mg
      kg(-1)) inhibited the ability of gentamicin to increase the levels of creatinine
      and urea. Furthermore, both light and electron microscopic evaluation confirmed
      the nephroprotective effect of the higher dose of trapidil. The level of the
      stable nitric oxide (NO) metabolite, nitrite, was also increased by trapidil. In
      conclusion, trapidil at a higher dose may protect against gentamicin
      nephrotoxicity. The mechanism underlying trapidil nephroprotection is not known,
      but may result from the antagonism of platelet-derived growth factor (PDGF),
      vasodilatation, inhibition of trombosit aggregation, and/or NO release.

PMID- 11592869
TI  - Baclofen prevents hypoxia-induced consolidation impairment for passive avoidance
      in rats.
AB  - We investigated the effects of baclofen, a selective GABA-B receptor agonist, on
      certain behaviours in rats after short-term hypoxia, as a model of experimentally
      induced amnesia. Baclofen given intraperitoneally (i.p.) in a dose of 0.25 mg kg(
      1) increased the number of crossings and bar approaches in the open field, but
      was ineffective in the passive avoidance tests; it also shortened the time spent
      in open arms and reduced the number of open arms entries in an elevated 'plus'
      maze, being a measure of anxiety. Hypoxia (2% O2, 98% N2) within 4 min profoundly
      impaired locomotor activity, consolidation and retrieval of conditioned
      responses, and exhibited a proaxiogenic effect in the elevated 'plus' maze in
      rats--it reduced the time spent in open arms and the number of entries to closed
      and open arms. Baclofen's effect on locomotor and exploratory activity was
      substantially impaired after hypoxia, i.e. rats exhibited a significant reduction
      in those activities. This agonist of GABA-B receptor used before hypoxia
      significantly improved consolidation, but had no effect on retrieval. In the
      elevated 'plus' maze rats pre-treated with baclofen and then subjected to hypoxia
      prolonged the time spent in open arms, reduced the time spent in closed arms, and
      increased the number of entries to the arms, i.e. exhibited anxiolytic effect. We
      conclude, therefore, that baclofen improved consolidation of passive avoidance in
      rats undergoing hypoxia.

PMID- 11592871
TI  - A self-folding metallocavitand.
AB  - The synthesis and characterization of novel metallocavitand 6 are described. This
      is a covalent hybrid of a deepened, self-folding cavity and a Zn-phenanthroline
      fragment. Host 6 features a large molecular cavity of approximately 8 x 10 A
      dimensions, and the metal binding site is directed in toward the cavity. Binding
      abilities of the metallocavitand in solution was demonstrated for quinuclidine 11
      and Dabco 12 using UV-vis and 1H NMR spectroscopy. Intramolecular hydrogen bonds
      at the upper rims of cavitand 6 resist the unfolding of the inner cavities and
      thereby increase the energetic barrier to guest exchange. The exchange is slow on
      the NMR time scale (at ambient temperatures, CD2Cl2), and kinetically stable
      complexes result. Both the polyaromatic cavity and metallosite participate
      simultaneously in the binding event. Zinc-containing deep cavities may be
      attractive as catalytic chambers for hydrolysis and esterification.

PMID- 11592870
TI  - The rise and fall of compartmental analysis.
AB  - The concept of compartment evolved in the contexts of radioactivity, physiology,
      pharmacology and tracer kinetics. Recently compartmental models have been
      compared with 'physiological models', even though in most cases the same, or
      stricter hypotheses, are necessary for the validity of these latter models. This
      paper shows that the methods of compartmental analysis are valid only if some
      specific hypotheses are valid.

PMID- 11592873
TI  - Asymmetric mono-oxazine: an inevitable product from Mannich reaction of
      benzoxazine dimers.
AB  - The Mannich reaction is detailed, which was carried out on benzoxazine dimers
      under various conditions, that is, temperature, reaction time, and solvents.
      Against our expectation, in any condition, instead of generating a disubstitution
      oxazine compound, the reaction gives a product with only a single oxazine ring, a
      mono-oxazine benzoxazine dimer, as characterized by FT-IR, 1H NMR, 13C NMR, 2D
      NMR (1H-1H COSY, 1H-13C HMQC, and 1H-13C HMBC), and EA. The asymmetrical reaction
      is found to be based on the original structure of the benzoxazine dimer which has
      two phenol rings in a different stability as clarified by X-ray structure
      analysis of the single crystal. All types of benzoxazine dimers indicate the
      specific structure with a pair of inter- and intramolecular hydrogen bonds. The
      bond distance indicates that the intramolecular hydrogen bonding is very strong,
      while the packing structure emphasizes the high stability of the dimer unit and
      implies the deactivation of one phenol ring in the benzoxazine dimer. In this
      contribution, we demonstrate one of the quite rare examples, showing how the
      stereostructure of the reactant molecule is an important factor to control the
      reaction and give an asymmetric product which we never expected when considering
      only the chemical formula.

PMID- 11592872
TI  - Synthesis and biological evaluation of analogues of the antibiotic pantocin B.
AB  - Strains of the bacteria Erwinia herbicola produce antibiotics that effectively
      control E. amylovora, the bacterial pathogen responsible for the plant disease
      fire blight. Pantocin B was the first of these antibiotics to be characterized,
      and a flexible synthesis of various analogues is reported. Embedded in the
      "pseudo-tripeptide" backbone of pantocin B are a methylenediamine and a methyl
      sulfone, both unusual structural features in natural products. The peptidic
      nature of pantocin B facilitated a series of structure-activity relationship
      studies that probed the roles of these functional groups in determining the
      biological activity of pantocin B. A clear demarcation of the roles between the N
      and C-terminal portions of the antibiotic was determined as a result of the
      structure-activity relationship studies. The N-terminal L-alanyl group is needed
      for cellular import but not for interaction with the intracellular target, the
      arginine biosynthetic enzyme N-acetylornithine aminotransferase. The
      methylenediamine and methyl sulfone portions were found to be essential for
      antibiotic activity, presumably due to extensive interactions with N
      acetylornithine aminotransferase.

PMID- 11592874
TI  - Bimolecular kinetic studies with high-temperature gas-phase 19F NMR:
      cycloaddition reactions of fluoroolefins.
AB  - A gas-phase NMR kinetic technique has been used for the first time to obtain
      accurate measurements of rate constants of some bimolecular, second-order
      cycloaddition reactions. As a test of the potential use of this technique for the
      study of second-order reactions, the rate constants and the activation parameters
      for the cyclodimerization reactions of chlorotrifluoroethylene (CTFE) and
      tetrafluoroethylene (TFE) were determined in the temperature range 240-340
      degrees C, using a commercial high-temperature NMR probe. Obtaining excellent
      agreement of the results with published data, the technique was then applied to
      the reaction of 1,1-difluoroallene with 1,3-butadiene, the results of which
      indicate that the use of gas-phase NMR for reaction kinetics is particularly
      valuable when a reagent is available only in small amounts and in cases where
      there are several competing processes occurring simultaneously. The major
      processes observed in this reaction are regioselective [2+2] and [2+4]
      cycloadditions, whose rates and activation parameters were determined [k2 = 9.3 x
      10(6) exp(-20.1 kcal x mol(-1)/RT) L/mol(-1) x s(-1) and k3 = 1.2 x 10(6) exp(
      18.4 kcal x mol(-1)/RT) L/mol(-1) x s(-)(1), respectively] in the temperature
      range 130-210 degrees C.

PMID- 11592875
TI  - Electropolymerization of Pd(II) complexes containing phosphinoterthiophene
      ligands.
AB  - A series of Pd complexes of 3'-diphenylphosphino-2,2':5'2' '-terthiophene (1a,
      dppterth) in which the metal is coordinated in three different modes have been
      prepared and electropolymerized, resulting in the formation of conductive thin
      films. In [Pd2(mu-Cl2)(dppterth-P,C3)2] (3a) the metal is P,C-coordinated, in
      [PdCl2(dppterth-P)2] (4a) the coordination is monodentate via the phosphine, and
      in [Pd(dppterth-P,C3)(dppterth-P,S1)][PF6] (5a) both P,C- and P,S-coordination
      modes are found. In 5a, the coordinated thiophene is hemilabile and may be
      displaced by reaction with more strongly coordinating ligands such as
      isocyanides. To probe the effect of blocking the alpha-position of the terthienyl
      moiety with methyl groups, 3'-diphenylphosphino-5-methyl-2,2':5'2' '-terthiophene
      (1b, Me-dppterth) and 3'-diphenylphosphino-5,5' '-dimethyl-2,2':5'2' '
      terthiophene (1c, Me2-dppterth) were prepared, and the corresponding series of Pd
      complexes was synthesized. One of these complexes, [Pd(Me2-dppterth-P,C3)(Me2
      dppterth-P,S1)][PF6] (5c), has been crystallographically characterized. The
      electropolymerized films prepared from 5a react with isonitriles, and shifts in
      the absorption spectra of the electropolymerized materials are observed upon
      reaction. A Pd complex has also been prepared from 5-diphenylphosphino-2,2':5'2'
      '-terthiophene (2, 5dppterth), and this complex has been electropolymerized. All
      the electropolymerized thin films have been characterized using EDX analysis,
      which demonstrates good correspondence with the elemental analysis of the
      respective monomers, and the maximum conductivities of the films are near 10(-4)
      S x cm(-1). Comparing the electropolymerization behavior of the complexes, along
      with their electrochemical and spectroscopic data, allows conclusions to be drawn
      regarding the involvement of pi-delocalization and the metal group in the
      conductivity of the materials.

PMID- 11592876
TI  - FR901464: total synthesis, proof of structure, and evaluation of synthetic
      analogues.
AB  - The natural product FR901464 (1) was isolated by the Fujisawa Pharmaceutical Co.
      and shown to have intriguing biological properties including impressive antitumor
      activity. In this paper we describe the first total synthesis of 1 in full
      detail. A chiral building block synthetic strategy was used to assemble the
      target: optically active components were generated using asymmetric catalytic
      reactions, and these fragments were coupled together at a late stage in a
      convergent synthesis. In particular, a versatile, asymmetric hetero-Diels-Alder
      (HDA) reaction was developed in the context of this synthesis and used with great
      effectiveness for the preparation of the two densely functionalized pyran rings.
      The flexible nature of the synthetic route also allowed us to prepare a series of
      analogues of 1. These compounds were used to prove the relative stereochemistry
      of the natural product as well as to probe the importance of certain structural
      features of FR901464 with regard to biological activity.

PMID- 11592877
TI  - Theoretical, thermodynamic, spectroscopic, and structural studies of the
      consequences of one-electron oxidation on the Fe-X bonds in 17- and 18-electron
      Cp*Fe(dppe)X complexes (X = F, Cl, Br, I, H, CH3).
AB  - The compounds Cp*Fe(dppe)X ([Fe]X) and the corresponding cation radicals [Fe*]X*+
      are available for the series X = F, Cl, Br, I, H, CH3. This has allowed for a
      detailed investigation of the dependence of the nature of Fe-X bonding on the
      identity of X and the oxidation state (charge) of the complex. Cyclic voltammetry
      demonstrates that the electrode potentials for the [Fe]X0/+ couples decrease in
      the order I > Br > Cl > H > F > CH3. An "inverse halide order" is seen, in which
      the most electronegative X leads to the most easily oxidized complex. This
      suggests that F is the best donor among the halides. The halide trend is also
      reflected in NMR spectroscopic data. Mossbauer spectroscopy data also suggest
      that the F ligand is a strong donor (relative to H and CH3) in [Fe*]X*+. DFT
      calculations on CpFe(dpe)X ([Fe]X) model complexes nicely reproduce the trend in
      the electrode potentials for the [Fe*]X0/+ couples. Analysis of the theoretical
      data within the halogen series indicates that the energy of the [Fe]X HOMO does
      not correlate with the extent of its Fe(d(pi))-X(p(pi)) antibonding character,
      which varies in the order I > Br > Cl > F, but rather depends on the
      destabilizing electrostatic effect caused by X. This effect varies in the order F
      > Cl > Br > I. A thermochemical cycle that incorporates the [Fe*]X0/+ and
      [Fe*]0/+ electrode potentials was used to investigate the effect of the oxidation
      state of the complex on the homolytic bond dissociation energy (BDEhom), defined
      for the processes Fe-X --> Fe* + X* and Fe-X*+ --> Fe*+ + X*. For all X, it was
      found that a one-electron oxidation leads to a weakening of the Fe-X bond. This
      trend was reproduced by the DFT calculations. On the other hand, IR nu(Fe-X)
      spectroscopy data showed an increase in the stretching frequencies for X = H and
      Cl upon oxidation. X-ray crystallographic data showed a shortening of the Fe-Cl
      bond upon oxidation. The trends in IR and Fe-Cl bond distances were reproduced in
      the DFT calculations. The combined data therefore suggest that oxidation leads to
      weaker, but shorter, Fe-X bonds. A second thermochemical cycle was applied to
      investigate the effect of the one-electron oxidation on the heterolytic bond
      dissociation energies (BDEhet), defined for the processes Fe-X --> Fe+ + X- and
      Fe-X*+ --> Fe2+ + X-. In this case, the oxidation led to bond strengthening in
      all cases. The computed BDE values have been analyzed within Ziegler's transition
      state methodology and decomposed into two components, one electrostatic and one
      covalent, describing the interaction between the unrelaxed fragments. In all the
      computed BDEhom and BDEhet values of the [Fe]X models the electrostatic component
      is important. This helps to understand their respective variations upon
      oxidation.

PMID- 11592878
TI  - Adsorption dynamics of gases and vapors on the nanoporous metal organic framework
      material Ni2(4,4'-bipyridine)3(NO3)4: guest modification of host sorption
      behavior.
AB  - This study combines measurements of the thermodynamics and kinetics of guest
      sorption with powder X-ray diffraction measurements of the nanoporous metal
      organic framework adsorbent (host) at different adsorptive (guest) loadings. The
      adsorption characteristics of nitrogen, argon, carbon dioxide, nitrous oxide and
      ethanol and methanol vapors on Ni2(4,4'-bipyridine)3(NO3)4 were studied over a
      range of temperatures as a function of pressure. Isotherm steps were observed for
      both carbon dioxide and nitrous oxide adsorption at approximately 10-20% of the
      total pore volume and at approximately 70% of total pore volume for methanol
      adsorption. The adsorption kinetics obey a linear driving force (LDF) mass
      transfer model for adsorption at low surface coverage. At high surface coverage,
      both methanol and ethanol adsorption follow a combined barrier
      resistance/diffusion model. The rates of adsorption in the region of both the
      carbon dioxide and methanol isotherm steps were significantly slower than those
      observed either before or after the step. X-ray diffraction studies at various
      methanol loadings showed that the host structure disordered initially but
      underwent a structural change in the region of the isotherm step. These isotherm
      steps are ascribed to discrete structural changes in the host adsorbent that are
      induced by adsorption on different sites. Isotherm steps were not observed for
      ethanol adsorption, which followed a Langmuir isotherm. Previous X-ray
      crystallography studies have shown that all the sites are equivalent for ethanol
      adsorption on Ni2(4,4'-bipyridine)3(NO3)4, with the host structure undergoing a
      scissoring motion and the space group remaining unchanged during adsorption. The
      activation energies and preexponential factors for methanol and ethanol
      adsorption were calculated for each pressure increment at which the linear
      driving force model was obeyed. There was a good correlation between activation
      energy and ln(preexponential factor), indicating a compensation effect. The
      results are discussed in terms of reversible adsorbate/adsorbent (guest/host)
      structural changes and interactions and the adsorption mechanism. The paper
      contains the first evidence of specific interactions between guests and
      functional groups leading to structural change in flexible porous coordination
      polymer frameworks.

PMID- 11592879
TI  - Experimental evidence for the noninnocence of o-aminothiophenolates: coordination
      chemistry of o-iminothionebenzosemiquinonate(1-) pi-radicals with Ni(II), Pd(II),
      Pt(II).
AB  - The ligand 2-mercapto-3,5-di-tert-butylaniline, H[L(AP)], an o-aminothiophenol,
      reacts with metal(II) salts of Ni and Pd in CH3CN or C2H5OH in the presence of
      NEt3 under strictly anaerobic conditions with formation of beige to yellow cis
      [M(II)(L(AP))2] (M = Ni (1), Pd (2)) where (L(AP))1- represents the o
      aminothiophenolate(1-) form. The crystal structure of cis
      [Pd(II)(L(AP))2][HN(C2H5)3][CH3CO2] has been determined by X-ray crystallography.
      In the presence of air the same reaction produces dark blue solutions from which
      mixtures of the neutral complexes trans/cis-[M(II)(L(ISQ))2] (M = Ni (1a/1b), Pd
      (2a/2b), and Pt (3a/3b)) have been isolated as dark blue-black solid materials.
      By using HPLC the mixture of 3a/3b has been separated into pure samples of 3a and
      3b, respectively; (L(ISQ))1- represents the o-iminothionebenzosemiquinonate(1-)
      pi-radical. The structures of 1a.dmf and 3a.CH2Cl2 have also been determined. All
      compounds are square-planar and diamagnetic. 1H NMR spectroscopy established the
      cis <==> trans equilibrium of 1a/1b, 2a/2b, and 3a/3b in CH2Cl2 solution where
      the isomerization rate is very fast for the Ni, intermediate for the Pd, and very
      slow for the Pt species. It is shown that the electronic structures of 1a/1b,
      2a/2b, 3a, and 3b are best described as diradicals with a singlet ground state.
      The spectro- and electrochemistries of all complexes display the usual full
      electron transfer series where the monocation, the neutral species, the mono- and
      dianions have been spectroscopically characterized. X-band EPR spectra of the
      monocations [1a/1b]+ and [3a]+ support the assignment of an oxidation-state
      distribution as predominantly [M(II)(L(ISQ))(L(IBQ))]+ where (L(IBQ))0 represents
      the o-iminothionequinone level. In contrast, the EPR spectra of the monoanions
      [1a/1b]- and [3a]- indicate an [M(II)(L(ISQ))(L(AP)-H)]- distribution but with a
      significant contribution of the [M(I)(L(ISQ))(2)]- resonance hybrid; (L(AP)-H)2-
      represents the o-imidothiophenolato(2-) oxidation level. Analysis of the
      geometric features of 120 published structures of complexes containing ligands of
      the o-aminothiophenolate type show that high precision X-ray crystallography
      allows to discern the differing protonation and oxidation levels of these
      ligands. o-Aminothiophenolates are unequivocally shown to be noninnocent ligands;
      the (L(ISQ))1- radical form is quite prevalent in coordination compounds and the
      electronic structure of a number of published complexes must be reconsidered.

PMID- 11592880
TI  - Steric barrier to bathorhodopsin decay in 5-demethyl and mesityl analogues of
      rhodopsin.
AB  - Absorbance difference spectra were recorded from 20 ns to 1 micros after 20
      degrees C photoexcitation of artificial visual pigments derived either from 5
      demethylretinal or from a mesityl analogue of retinal. Both pigments produced an
      early photointermediate similar to bovine bathorhodopsin (Batho). In both cases
      the Batho analogue decayed to a lumirhodopsin (Lumi) analogue via a blue-shifted
      intermediate, BSI, which formed an equilibrium with the Batho analogue. The
      stability of 5-demethyl Batho, even though the C8-hydrogen of the polyene chain
      cannot interact with a ring C5-methyl group to provide a barrier to Batho decay,
      raises the possibility that the 5-demethylretinal ring binds oppositely from
      normal to form a pigment with a 6-s-trans ring-chain conformation. If 6-s-trans
      binding occurred, the ring C1-methyls could replace the C5-methyl in its
      interaction with the chain C8-hydrogen to preserve the steric barrier to Batho
      decay, consistent with the kinetic results. The possibility of 6-s-trans binding
      for 5-demethylretinal also could account for the unexpected blue shift of 5
      demethyl visual pigments and could explain why 5-demethyl artificial pigments
      regenerate so slowly. Although the mesityl analogue BSI's absorption spectrum was
      blue-shifted relative to its pigment spectrum, the blue shift was much smaller
      than for rhodopsin's or 5-demethylisorhodopsin's BSI. This suggests that
      increased C6-C7 torsion may be responsible for some of BSI's blue shift, which is
      not the case for mesityl analogue BSI either because of reduced spectral
      sensitivity to C6-C7 torsion or because the symmetry of the mesityl retinal
      analogue precludes having 6-s-cis and 6-s-trans conformers. The similarity of the
      mesityl analogue BSI and native BSI lambda(max) values supports the idea that BSI
      has a 6-s angle near 90 degrees, a condition which could disconnect the chain
      (and BSI's spectrum) from the double bond specifics of the ring.

PMID- 11592882
TI  - Two photon absorption properties of 1,3,5-tricyano-2,4,6-tris(styryl)benzene
      derivatives.
AB  - Two-photon absorption (TPA) properties of 1,3,5-tricyano-2,4,6
      tris(styryl)benzene derivatives have been investigated. Comparison of the
      absorption and fluorescence spectra reveals that these compounds show large
      Stokes shifts, which increase gradually as the conjugation length increases. One
      photon absorption and excitation spectra are similar except that the latter
      exhibit several peaks near lambda(max). It is also found that the one- and two
      photon-induced fluorescence excitation spectra are quite similar, which indicates
      that the one- and two-photon allowed-excited states are the same. The peak TPA
      cross section values (delta(max)) measured with nanosecond pulses by the two
      photon-induced fluorescence method are in the range (50-2620) x 10(-50) cm4
      s/photon. The delta(max) value increases as the donor strength and conjugation
      length increase. A linear relationship is observed between delta(max) and beta,
      and this delta-beta relationship is found to serve as a useful synthetic strategy
      for the design of novel TPA dyes with the octupolar structure.

PMID- 11592881
TI  - Modeling furanose ring dynamics in DNA.
AB  - Determination of the conformational flexibility of the furanose ring is of vital
      importance in understanding the structure of DNA. In this work we have applied a
      model of furanose ring motion to the analysis of deuterium line shape data
      obtained from sugar rings in solid hydrated DNA. The model describes the angular
      trajectories of the atoms in the furanose ring in terms of pseudorotation
      puckering amplitude (q) and the pseudorotation puckering phase phi. Fixing q, the
      motion is thus treated as Brownian diffusion through an angular-dependent
      potential U(phi). We have simulated numerous line shapes varying the adjustable
      parameters, including the diffusion coefficient D, pseudorotation puckering
      amplitude q, and the form of the potential U(phi). We have used several forms of
      the potential, including equal double-well potentials, unequal double-well
      potentials, and a potential truncated to "second order" in the Fourier series. To
      date, we have obtained best simulations for both equilibrium and nonequilibrium
      (partially relaxed) solid-state deuterium NMR line shapes for the sample [2' '
      2H]-2'-deoxycytidine at the position C3 (underlined) in the DNA sequence
      [d(CGCGAATTCGCG)]2, using a double-well potential with an equal barrier height of
      U(0) = 5.5k(B)T ( approximately 3.3 kcal/mol), a puckering amplitude of q = 0.4
      A, and a diffusion coefficient characterizing the underlying stochastic jump rate
      D = 9.9 x 10(8) Hz. Then the rate of flux for the C-D bond over the barrier,
      i.e., the escape velocity or the overall rate of puckering between modes, was
      found to be 0.7 x 10(7) Hz.

PMID- 11592883
TI  - On the apparently anomalous distance dependence of charge-transfer rates in 9
      amino-6-chloro-2-methoxyacridine-modified DNA.
AB  - From previous thermal and photoinduced charge-transfer reactions in duplex DNA
      there is accumulative evidence for an attenuation parameter beta of the distance
      dependence in the range 0.6-0.8 A(-1), with the exception of one specific system
      exhibiting beta = 1.5 A(-1) which is reinvestigated in this paper. Femtosecond to
      nanosecond time-resolved pump-probe spectroscopy has been used to follow
      photoinduced charge-shift dynamics in DNA duplexes containing a covalently
      appended, protonated 9-alkylamino-6-chloro-2-methoxyacridine chromophore. This
      acridine derivative (X+) resides in the DNA duplex at a specific abasic site,
      which is highly defined as reflected in the monoexponentiality of the kinetics.
      In the presence of only neighboring A:T base pairs, no charge transfer occurs
      within the excited-state lifetime (18 ns) of the chromophore. However, the
      presence of a guanine nucleobase as either a nearest neighbor or with one
      interspersed A:T base pair does result in fluorescence quenching. In the case of
      nearest neighbors, the intermediate radical state X* is formed within 4 ps and
      decays on the 30 ps time scale. Placing one A:T base pair between the X+ and
      guanine slows down the forward transfer rate by 3 orders of magnitude,
      corresponding to an apparent beta value of >2.0 A(-1). This dramatic decrease in
      the rate is due to a change in charge-transfer mechanism from a (nearly)
      activationless to a thermally activated regime in which the forward transfer is
      slower than the back transfer and the X* state is no longer observed. These
      observations indicate that the distance dependence of charge injection in the X+
      labeled DNA duplex is not solely caused by a decrease in electronic couplings but
      also by a concomitant increase of the activation energy with increasing distance.
      This increase in activation energy may result from the loss of driving force due
      to excited-state relaxation competing with charge transfer, or reflect distance
      dependent changes in the energetics, predominantly of the low-frequency
      reorganization energy in this charge-shift reaction, on purely electrostatic
      grounds. To test the hypothesis of distance-dependent activation energy, guanine
      has been replaced by 7-deazaguanine, its easier-to-oxidize purine analogue. In
      these duplexes, a similar change of charge-transfer mechanism is found. However,
      consistent with an a priori larger driving force this change occurs at a larger
      donor-acceptor separation than in the X+-guanine systems. Independent of the
      detailed contributions to the distance-dependent activation energy, this
      phenomenon illustrates the complex nature of experimental beta values.

PMID- 11592884
TI  - Conformational dynamics of the transcriptional regulator CooA protein studied by
      subpicosecond mid-infrared vibrational spectroscopy.
AB  - CooA, which is a transcriptional regulator heme protein allosterically triggered
      by CO, is studied by femtosecond visible-pump mid-IR-probe spectroscopy.
      Transient bleaching upon excitation of the heme in the Soret band is detected at
      approximately 1979 cm(-1), which is the absorption region of the CO bound to the
      heme. The bleach signal shows a nonexponential decay with time constants of 56
      and 290 ps, caused by the rebinding of the CO to the heme. About 98% of
      dissociated CO recombines geminately. The geminate recombination rate in CooA is
      significantly faster than those in myoglobin and hemoglobin. The angle of the
      bound CO with respect to the porphyrin plane is calculated to be about 78 degrees
      on the basis of the anisotropy measurements. A shift of the bleached mid-IR
      spectrum of the bound CO is detected and has a characteristic time of 160 ps. It
      is suggested that the spectral shift is caused by a difference in the frequency
      of the bound CO in different protein conformations, particularly in an active
      conformation and in an intermediate one, which is on the way toward an inactive
      conformation. Thus, the biologically relevant conformation change in CooA was
      traced. Possible assignment of the observed conformation change is discussed.

PMID- 11592885
TI  - 1H and 13C NMR investigation of the influence of nonligated residue contacts on
      the heme electronic structure in cyanometmyoglobin complexes reconstituted with
      centro- and pseudocentrosymmetric hemins.
AB  - The 1H and 13C chemical shifts for the heme methyls of low-spin, ferric sperm
      whale cyanometmyoglobin reconstituted with a variety of centrosymmetric and
      pseudocentrosymmetric hemins have been recorded and analyzed to shed light on the
      nature of heme-protein contacts, other than that of the axial His, that modulate
      the rhombic perturbation to the heme's in-plane electronic asymmetry. The very
      similar 1H dipolar shifts for heme pocket residues in all complexes yield
      essentially the same magnetic axes as in wild type, and the resultant dipolar
      shifts allow the direct determination of the heme methyl proton and 13C contact
      shifts in all complexes. It is demonstrated that, even when the magnetic axes and
      anisotropies are known, the intrinsic uncertainties in the orientational
      parameters lead to a sufficiently large uncertainty in dipolar shift that the
      methyl proton contact shifts are inherently significantly less reliable
      indicators of the unpaired electron spin distribution than the methyl 13C contact
      shifts. The pattern of the noninversion symmetry in 13C contact shifts in the
      centro- or pseudocentrosymmetric hemes is shown to correlate with the positions
      of aromatic rings of Phe43(CD1) and His97(FG3) parallel to, and in contact with,
      the heme. These results indicate that such pi-pi interactions significantly
      perturb the in-plane asymmetry of the heme pi spin distribution and cannot be
      ignored in a quantitative interpretation of the heme methyl 13C contact shifts in
      terms of the axial His orientation in b-type hemoproteins.

PMID- 11592886
TI  - Is there a minimum size for aqueous doubly charged metal cations?
AB  - A major feature of the chemistry of multiply charged solvated metal ions is
      dissociative charge transfer. It happens because the second ionization potential
      (IP) of a metal atom usually exceeds the first IP of a solvent molecule. This
      raises the issue of whether there is a minimum number of ligands below which the
      species would charge-separate spontaneously. To elucidate this, doubly charged
      aqueous cations of most common divalent metals (group 2 elements Mn, Fe, Co, Ni,
      Zn, Cd, and Cu) have been generated using electrospray and examined by collision
      induced dissociation in a triple-quadrupole mass spectrometer. We have clearly
      observed the monoaqua complexes for all aforementioned doubly charged metal ions,
      except Be for which the smallest complex found is the dihydrate. We have also
      systematically revisited the matter of critical size--the maximum number of
      ligands at which dissociative charge transfer is competitive with simple ligand
      loss.

PMID- 11592887
TI  - Negative differential resistance behavior in conjugated molecular wires
      incorporating spacers: a quantum-chemical description.
AB  - Recent experimental studies have demonstrated that single molecules or a small
      number of self-assembled molecules can perform the basic functions of traditional
      electronic components, such as wires and diodes. In particular, molecular wires
      inserted into nanopores can be used as active elements for the fabrication of
      resonant tunneling diodes (RTDs), whose I/V characteristics reveal a Negative
      Differential Resistance (NDR) behavior (i.e., a negative slope in the I/V curve).
      Here, quantum-chemical calculations are used to describe on a qualitative basis
      the mechanism leading to NDR in polyphenylene-based molecular wires incorporating
      saturated spacers. This description is based on the characterization of the
      evolution of the wire electronic structure as a function of a static electric
      field applied along the molecular axis, which simulates the driving voltage
      between the two electrodes in the RTD devices. We illustrate that the main
      parameters controlling the NDR behavior can be modulated through molecular
      engineering of the wires.

PMID- 11592888
TI  - [2+2] versus [3+2] addition of metal oxides across C=C double bonds: toward an
      understanding of the surprising chemo- and periselectivity of transition-metal
      oxide additions to ketene.
AB  - The peri-, chemo-, stereo-, and regioselectivity of the addition of the
      transition-metal oxides OsO4 and LReO3 (L = O-, H3PN, Me, Cp) to ketene were
      systematically investigated using density-functional methods. While metal-oxide
      additions to ethylene have recently been reported to follow a [3+2] mechanism
      only, the calculations reveal a strong influence of the metal on the
      periselectivity of the ketene addition: OsO4 again prefers a [3+2] pathway across
      the C=C moiety whereas, for the rhenium oxides LReO3, the [2+2] barriers are
      lowest. Furthermore, a divergent chemoselectivity arising from the ligand L was
      found: ReO4- and (H3PN)ReO3 add across the C=O bond while MeReO3 and CpReO3 favor
      the addition across the C=C moiety. The calculated energy profile for the MeReO3
      additions differs from the CpReO3 energy profile by up to 45 kcal/mol due to the
      stereoelectronic flexibility of the Cp ligand adopting eta5, eta3, and eta1
      bonding modes. The selectivity of the cycloadditions was rationalized by the
      analysis of donor-acceptor interactions in the transition states. In contrast,
      metal-oxide additions to diphenylketene probably follow a different mechanism: We
      give theoretical evidence for a zwitterionic intermediate that is formed by
      nucleophilic attack at the carbonyl moiety and undergoes a subsequent cyclization
      yielding the thermodynamically favored product. This two-step pathway is in
      agreement with the results of recent experimental work.

PMID- 11592889
TI  - Single-molecule vibrations, conformational changes, and electronic conductivity
      of five-membered heterocycles.
AB  - Using an ultrahigh vacuum scanning tunneling microscope (STM), we have explored
      the interactions of isolated five-membered heterocycles, pyrrole, thiophene,
      pyrrolidine, and tetrahydrothiophene, with the Cu(001) surface at 9 K.
      Pyrrolidine was also studied on the Ag(001) surface. Important distinctions in
      bonding, vibrational spectra, and vibrationally mediated negative differential
      resistance were observed with the aid of single-molecule inelastic electron
      tunneling spectroscopy (STM-IETS).

PMID- 11592890
TI  - Room-temperature alkyl-alkyl Suzuki cross-coupling of alkyl bromides that possess
      beta hydrogens.

PMID- 11592891
TI  - Dehydration reactions in water. Surfactant-type Bronsted acid-catalyzed direct
      esterification of carboxylic acids with alcohols in an emulsion system.

PMID- 11592892
TI  - Origins of asymmetric amplification in autocatalytic alkylzinc additions.

PMID- 11592893
TI  - Guest intercalation at corrugated surface of host monolayer crystal on water:
      cholesteryl-L-glutamate and water-soluble amino acids.

PMID- 11592895
TI  - Using a synthetic receptor to create an optical-sensing ensemble for a class of
      analytes: a colorimetric assay for the aging of scotch.

PMID- 11592894
TI  - Detection of aminium ion intermediates: N-cyclopropyl versus N-carboxymethyl
      groups as reporters.

PMID- 11592896
TI  - An experimental and computational analysis of the formation of the terminal
      nitrido complex (eta3-Cp*)2Mo(N)(N3) by elimination of N2 from Cp*2Mo(N3)2: the
      barrier to elimination is strongly influenced by the exo versus endo
      configuration of the azide ligand.

PMID- 11592898
TI  - Toward the biaxial nematic phase of low molar mass thermotropic mesogens:
      substantial molecular biaxiality in covalently linked rod-disk dimers.

PMID- 11592897
TI  - Nanomolar E-selectin inhibitors: 700-fold potentiation of affinity by multivalent
      ligand presentation.

PMID- 11592899
TI  - Complete structure of the mycolactones.

PMID- 11592900
TI  - Fluorous triphasic reactions: transportative deprotection of fluorous silyl
      ethers with concomitant purification.

PMID- 11592901
TI  - Human cytosolic iron regulatory protein 1 contains a linear iron-sulfur cluster.

PMID- 11592902
TI  - High-field EPR characterization of manganese reconstituted superoxide dismutase
      from Rhodobacter capsulatus.

PMID- 11592903
TI  - Discovery of a catalytic asymmetric phosphorylation through selection of a
      minimal kinase mimic: a concise total synthesis of D-myo-inositol-1-phosphate.

PMID- 11592904
TI  - Design, synthesis, and utility of a support-bound tert-butanesulfinamide.

PMID- 11592905
TI  - A crystallographically characterized nine-coordinate calcium-phosphocitrate
      complex as calcification inhibitor in vivo.

PMID- 11592906
TI  - Total synthesis of pamamycin-607.

PMID- 11592907
TI  - An efficient, single-source molecular precursor to silicoaluminophosphates.

PMID- 11592909
TI  - A hot molecule as an intermediate in multiphoton reactions: first photoinduced
      reactions of biphenylene.

PMID- 11592908
TI  - Biological relevance of metal binding before protein folding.

PMID- 11592910
TI  - Are heterogeneous catalysts precursors to homogeneous catalysts?

PMID- 11592911
TI  - Process characterization for metal-affinity chromatography of an Fc fusion
      protein: a design-of-experiments approach.
AB  - The utility of a design-of-experiments approach was investigated for process
      characterization of a metal-affinity chromatographic purification process for an
      Fc fusion protein. This approach gave a better understanding of some of the key
      process variables as well as robustness for this step in the purification
      process. Single-variable experiments were employed to screen some of the
      potentially important variables in this step. Ranges for these variables were set
      based on prior experience in clinical manufacturing with similar processes.
      Following these experiments, a fractional factorial study was employed to further
      investigate the most important variables and their interactions. Key operational
      variables that had an impact on step yield and eluate purity were identified. In
      addition, the study helped identify a worst-case scenario for the step purity and
      helped assure that the rest of the process would successfully purify the product.
      This paper demonstrates the utility of a design-of-experiments approach for the
      characterization and validation of process chromatography steps in downstream
      processing. In addition, this study emphasizes the utility of robustness studies
      early in process development and establishes a strategy for future robustness
      studies.

PMID- 11592912
TI  - Enhanced thermal stability of an alkaline protease, AprP, isolated from a
      Pseudomonas sp. by mutation at an autoproteolysis site, Ser-331.
AB  - The thermal stability of the alkaline protease extracellular subtilisin-type
      serine protease (AprP) from Pseudomonas sp. KFCC 10818 was improved by altering
      an amino acid residue at an autoproteolytic cleavage site. N-terminal sequence
      analysis of the autoproteolytic products of the protein revealed the presence of
      two cleavage sites, Ser-307 and Ser-331. To increase the thermal stability of the
      enzyme, serine residues of these sites were replaced with aspartate. The S331D
      mutant enzyme was successfully purified and characterized whereas the S307D
      mutant was not. The half-lives of the S331D mutant at 55 degrees C and 60 degrees
      C were 1.5 and 2.4 times longer than that of the wild-type enzyme, respectively.
      In addition, the catalytic efficiency was also enhanced.

PMID- 11592913
TI  - Characterization of trichobakin, a type I ribosome-inactivating protein from
      Trichosanthes sp. Bac Kan 8-98.
AB  - We have isolated a genomic clone encoding trichobakin (TBK), a type I ribosome
      inactivating protein from the plant Trichosanthes sp. Bac Kan 8-98 (family
      Cucurbitaceae), by PCR using specific primers designed from the cDNA sequences of
      alpha-trichosanthin. The sequence encoding mature TBK was constructed in the pET
      21d(+) vector for overexpression in Escherichia coli strain BL21(DE3). The
      recombinant protein was purified to homogeneity by CM-Sepharose chromatography on
      FPLC with a final yield of about 55 mg/l of culture. The protein has a molecular
      mass of about 27 kDa, as shown by SDS/PAGE and matrix-assisted laser-desorption
      ionization MS. It was found that the protein inhibited luciferase mRNA
      translation in the rabbit reticulocyte cell-free system with an IC(50) value
      (that which causes a 50% reduction of residual translational activity) of about
      3.5 pM. The rRNA N-glycosidase activity of the protein was also proved at the
      above-mentioned concentration after rRNAs were treated with acid aniline.

PMID- 11592914
TI  - Production of dextran from sucrose by a newly isolated strain of Leuconostoc
      mesenteroides (PCSIR-3) with reference to L. mesenteroides NRRL B-512F.
AB  - A newly isolated strain of Leuconostoc mesenteroides (PCSIR-3) produced a
      different dextran compared with that of L. mesenteroides NRRL B-512F. Different
      media compositions used for dextran production showed that media containing
      CaCl(2) produced dextran in higher quantities compared with other media. The
      viscosity of the dextran produced in different media varied in nature. Dextran
      from media 1 and 2 was of higher molecular mass compared with that from media 3,
      4 and 5. Dextran production is also effected by the sucrose concentration in the
      media. The higher the initial concentration of sucrose, the higher is the yield
      of dextran produced per unit volume; however, the percentage conversion of
      sucrose into dextran decreases. A continuous drop in pH was associated with
      growth and dextran production. The yield of dextran increases during the growth
      phase and maximum yield was obtained at the end of the exponential phase. Dextran
      produced by L. mesenteroides PCSIR-3 is quite different from the dextran produced
      by NRRL B-512F. Maximum dextran production from L. mesenteroides PCSIR-3 occurs
      in 18 h compared with 12 h for NRRL B-512F.

PMID- 11592915
TI  - Improvement of tagatose conversion rate by genetic evolution of thermostable
      galactose isomerase.
AB  - To enhance the isomerization rate of galactose into tagatose, a thermostable
      galactose isomerase, which was isolated from bacteria growing in a hot spring,
      was genetically improved using the error-prone PCR method. From 500 mutant
      clones, a clone showing improved conversion activity was selected. The sequence
      of the selected clone had five amino acid changes: His(228)-->Asp, Gly(384)-
      >Asp, Ser(393)-->Thr, Lys(428)-->Asn and Asp(475)-->Lys. The improved galactose
      isomerase had an 11-fold higher reaction rate than the original.

PMID- 11592916
TI  - Nisin production from Lactococcus lactis A.T.C.C. 7962 using supplemented whey
      permeate.
AB  - The influence of pH control and aeration (20% dissolved oxygen) on nisin
      production in a supplemented cheese whey permeate was examined during batch
      fermentation with Lactococcus lactis subsp. lactis A.T.C.C. 7962. A maximum nisin
      activity of 5280 i.u./ml of medium was observed in the raw extract of nisin after
      9 h of fermentation with a constant pH at 4.9. However, the fermentation was
      continued until 24 h, when a decrease in the nisin activity was observed. The pH
      control did not influence the nisin production and aeration of the culture medium
      increased cell growth (biomass) but not nisin activity. The yeast Kluyveromyces
      marxianus, used as an alternative method to control pH, has not been efficient.

PMID- 11592917
TI  - Expression, purification, immunological characterization and application of
      Escherichia coli-derived hepatitis C virus E2 proteins.
AB  - The envelope glycoprotein E2 of hepatitis C virus (HCV) has been shown to bind
      human target cells. Anti-E2 antibodies have been associated with both recovery
      from natural infection in humans and protection from challenge with homologous
      HCV in chimpanzees. Therefore E2 has become a major target for the development of
      anti-HCV vaccines. Two E2 fragments [amino acids (aa) 450-565 and aa 385-565]
      derived from a subtype 1b HCV genome were expressed as N-terminally hexahistidine
      tagged proteins in Escherichia coli and purified to over 85% purity. Both
      proteins were specifically recognized by homologous hepatitis-C-patient's serum
      on Western blotting, suggesting that these E. coli-derived E2 proteins displayed
      E2-specific antigenicity. E2-116 (aa 450-565) elicited strong antibody responses
      in BALB/c mice and rabbits. Rabbit antiserum raised against renatured E2-116
      (R(E2-116R)) was able to recognize subtype 1b and 1a E2 glycoproteins expressed
      in mammalian cells on Western blotting. E2-181 (aa 385-565) reacted with 40% of
      anti-HCV(+) patients' sera in ELISA. R(E2-116R) and E2-181 were successfully used
      in preliminary modified vaccinia virus Ankara- and DNA-based E2 vaccine studies
      for detecting antigen expression in vitro and assessing induced humoral immune
      responses in mice. The E2 proteins and rabbit antiserum reported here could find
      wider applications in the development of effective diagnostic, prophylactic and
      therapeutic measures against HCV.

PMID- 11592919
TI  - Stability enhancement of Escherichia coli penicillin G acylase by glycosylation
      with yeast mannan.
AB  - Penicillin G acylase (PGA) from Escherichia coli was cross-linked with mannan
      dialdehydes. Conjugates were prepared with molecular masses varying from 140 to
      580 kDa and containing from 18 to 50% (w/w) saccharides, the values depending on
      the reaction conditions (mannan/enzyme ratio), and by using mannans with
      different degrees of oxidation and weight-average molecular mass (M macro(w)).
      The pH- and thermo-stability of all preparations of glycosylated enzyme were
      improved remarkably, whereby the influence of the character of the linked mannan
      dialdehyde, its content, as well as the molecular mass of prepared
      glycoconjugates, on the stability of PGA, was evaluated. PGA glycosylated with
      the most oxidized mannan up to an M(w) of 490 kDa, containing 41% (w/w)
      saccharides, and retaining 90% of its original catalytic activity, showed the
      highest stability. The half-life of this PGA preparation increased significantly:
      13-fold at pH 3, 7-fold at pH 10, and 3.5-fold at pH 8 (all at 37 degrees C),
      compared with the native enzyme. At higher temperatures (50 degrees C) even more
      significant stabilization was evident, a 16-fold increase in half-life, from 18
      min to 289 min, at pH 8, being measured.

PMID- 11592918
TI  - Safety and preliminary immunogenicity of the recombinant outer membrane protein
      P64k of Neisseria meningitidis in human volunteers.
AB  - P64k is a meningococcal protein from Neisseria meningitidis that has been
      obtained by recombinant DNA technology. Recombinant P64k has been extensively
      characterized by physicochemical and immunological methods. Lately this protein
      has been found to act as a versatile immunological carrier for weak antigens in
      mice. In the present work, a Phase I clinical trial was carried out in healthy
      volunteers who received three inoculations of either placebo or recombinant P64k
      (20 or 50 microg). No severe adverse events occurred during the trial. Only mild
      adverse events in ten volunteers were observed. At 1 month after the third dose,
      15 out of 18 volunteers (83.3%) who received the recombinant antigen had a P64k
      specific antibody titre > or =1:100, as detected by ELISA. A fourth dose, given 9
      months after the third one, elicited a potent booster immune response in P64k
      vaccinees. Accordingly, these P64k formulations were considered safe and
      immunogenic in healthy human volunteers.

PMID- 11592920
TI  - Omapatrilat normalizes renal function curve in spontaneously hypertensive rats.
AB  - BACKGROUND: The present study was designed to analyze the chronic renal response
      to omapatrilat, a new vasopeptidase inhibitor, in spontaneously hypertensive rats
      (SHR). To that end, the renal and blood pressure response to a 4-day salt loading
      protocol was analyzed and the respective chronic renal curves constructed.
      RESULTS: In non treated animals, and under normal sodium intake (around 2
      mEq/day), mean arterial pressure (MAP), was significantly higher in the SHR as
      compared with the controls (WKY). After increasing salt intake (8 times normal),
      MAP did not change significantly in any group and the animals reached a normal
      sodium balance in four days. In a second group of animals, omapatrilat was given
      orally for 15 days at the dose of 40 mg/kg/day in the drinking water. In these
      omapatrilat-treated animals, and under normal sodium intake, MAP was
      significantly lower in both groups, although the antihypertensive effect was much
      greater in the SHR, so that the MAP of the SHR group was completely normalized
      and similar to the WKY-treated group. The subsequent elevation of sodium intake
      did not significantly elevate MAP in any group and the animals could manage the
      sodium excess as well as the non treated groups. CONCLUSIONS: These results
      indicate that chronic treatment with omapatrilat normalizes blood pressure in SHR
      without affecting adversely the renal ability to eliminate a sodium load. Chronic
      treatment with omapatrilat resets the chronic pressure natriuresis relationship
      of the SHR to a normal level, thus without altering the normal salt-independence
      of this arterial hypertension model.

PMID- 11592922
TI  - Preimplantation genetics: an explanation for poor human fertility?

PMID- 11592921
TI  - Collection of corneal impression cytology directly on a sterile glass slide for
      the detection of viral antigen: an inexpensive and simple technique for the
      diagnosis of HSV epithelial keratitis - a pilot study.
AB  - BACKGROUND: Herpes simplex keratitis (HSK) is a sight threatening ocular
      infection and occurs worldwide. A prompt laboratory diagnosis is often very
      useful. Conventional virology techniques are often expensive and time consuming.
      We describe here a highly economical, simple, rapid and sensitive technique for
      the collection of impression cytology, for the laboratory diagnosis of HSK.
      METHODS: Fifteen patients with a clinical diagnosis of HSK (either dendritic or
      geographic ulcers) and five patients with other corneal infections (Mycotic
      keratitis, n = 3, Bacterial keratitis, n = 2) were included in the study. Corneal
      impression cytology specimens were collected using a sterile glass slide with
      polished edges instead of a membrane, by pressing the surface of one end of the
      slide firmly, but gently on the corneal lesion. Additionally, corneal scrapings
      were collected following the impression cytology procedure. Impression cytology
      and corneal scrapings were stained by an immunoperoxidase or immunofluorescence
      assay for the detection of HSV-1 antigen using a polyclonal antibody to HSV-1.
      Corneal scrapings were processed for viral cultures by employing a shell vial
      assay. RESULTS: This simple technique allowed the collection of adequate corneal
      epithelial cells for the detection of HSV-1 antigen in a majority of the
      patients. HSV-1 antigen was detected in 12/15 (80%) cases while virus was
      isolated from 5/15 (33.3%) patients with HSK. All the patients with a clinical
      diagnosis of HSK (n = 15) were confirmed by virological investigations (viral
      antigen detection and/or viral cultures). HSV-1 antigen was detected in the
      impression cytology smears and corneal scrapings in 11/15 (73.3%) and 12/15 (80%)
      of the patients, respectively (P = 1.00). None of the patients in the control
      group were positive for viral antigen or virus isolation. Minimal background
      staining was seen in impression cytology smears, while there was some background
      staining in corneal scrapings stained by the immunoassays. CONCLUSIONS:
      Collection of impression cytology on a sterile glass slide is a simple, rapid and
      inexpensive technique for the diagnosis of HSK. Immunological techniques applied
      on such smears provide virological results within 2-5 hours. This technique could
      be modified for use in the diagnosis of other external eye diseases, which needs
      further evaluation.

PMID- 11592923
TI  - A multistep process for the dispersal of a Y chromosomal lineage in the
      Mediterranean area.
AB  - In this work we focus on a microsatellite-defined Y-chromosomal lineage (network
      1.2) identified by us and reported in previous studies, whose geographic
      distribution and antiquity appear to be compatible with the Neolithic spread of
      farmers. Here, we set network 1.2 in the Y-chromosomal phylogenetic tree, date it
      with respect to other lineages associated with the same movements by other
      authors, examine its diversity by means of tri- and tetranucleotide loci and
      discuss the implications in reconstructing the spread of this group of
      chromosomes in the Mediterranean area. Our results define a tripartite phylogeny
      within HG 9 (Rosser et al. 2000), with the deepest branching defined by alleles T
      (Haplogroup Eu10) or G (Haplogroup Eu9) at M172 (Semino et al. 2000), and a
      subsequent branching within Eu9 defined by network 1.2. Population distributions
      of HG 9 and network 1.2 show that their occurrence in the surveyed area is not
      due to the spread of people from a single parental population but, rather, to a
      process punctuated by at least two phases. Our data identify the wide area of the
      Balkans, Aegean and Anatolia as the possible homeland harbouring the largest
      variation within network 1.2. The use of recently proposed tests based on the
      stepwise mutation model suggests that its spread was associated to a population
      expansion, with a high rate of male gene flow in the Turkish-Greek area.

PMID- 11592924
TI  - Length variability and interspersion patterns of the HRAS1 minisatellite: a new
      approach for the reconstruction of human population relationships.
AB  - During recent years the HRAS1 minisatellite has been analysed by several authors
      because of its putative association with cancer susceptibility. The aim of this
      report is to test the usefulness of this minisatellite in investigating human
      population relationships. We have studied 370 chromosomes from two well
      differentiated populations: Galicia (North-west Iberia) and South-east Africa, as
      well as available data on allele length gene frequencies. The fragment analysis
      results show a strong tendency to differentiate between non-African and African
      populations. In spite of the usefulness of fragment analysis, the minisatellite
      variant repeat (MVR) approach of the HRAS1 minisatellite appears to be a more
      powerful method for use in human population studies, due to the high level of
      diversity of its interspersion pattern structures. In addition, this approach has
      allowed us to define some new structural characteristics of this minisatellite.
      Four different major groups of human HRAS1 minisatellite alleles could be
      distinguished following a structural criterion based on the MVR code.
      Furthermore, the characterisation of the HRAS1 minisatellite in chimpanzees
      revealed clear differences when compared to humans, not only with respect to the
      allele size but also to the internal structure.

PMID- 11592925
TI  - An HLA class-II allele frequent in Eskimos and Amerindians is found in the
      Tyrolean Ice Man.
AB  - DNA was extracted from specimens derived from the calcaneus of the Tyrolean Ice
      Man under sterile conditions in a laboratory, where no DNA extractions and PCR
      experiments had been performed before. Agarose gel electrophoresis and ethidium
      bromide staining did not reveal any evidence of genomic DNA in the preparation
      obtained, indicating a high degree of DNA degradation. Nevertheless, we performed
      PCR amplifications with this sample using primer pairs specific for HLA class II
      alleles. HLA-DRB and DQB1 alleles were amplified in a nested PCR approach. In one
      of the reactions, we observed a distinct amplification product, which we directly
      sequenced. By comparing the obtained nucleotide sequence with a database of HLA
      alleles we assigned the HLA-DRB1*1402 type to the amplified sample. None of the
      investigators involved possesses this allele, indicating that no contamination
      with modern DNA had occurred. The HLA-DRB1*1402 allele is extremely rare in
      Europe, but is common in Inuits and South American Indians and has previously
      only once been identified in the laboratory.

PMID- 11592926
TI  - Replication studies in longevity: puzzling findings in Danish centenarians at the
      3'APOB-VNTR locus.
AB  - In Danes we replicated the 3'APOB-VNTR gene/longevity association study
      previously carried out in Italians, by which the Small alleles (less than 35
      repeats) had been identified as frailty alleles for longevity. In Danes, neither
      genotype nor allele frequencies differed between centenarians and 20-64-year-old
      subjects. However, when Danish and Italian data were compared, a significant
      difference (p = 0.0004) was found between the frequencies of Small alleles in
      youths, which disappeared in centenarians (p = 0.290). Furthermore, the
      demographic-genetic approach revealed in Danes a significant gene-sex interaction
      relevant to Long alleles (more than 37 repeats). The different findings in
      Denmark and Italy suggest that gene/longevity associations are population
      specific, and heavily affected by the population-specific genetic and
      environmental history.

PMID- 11592927
TI  - Coeliac disease: follow-up linkage study provides further support for existence
      of a susceptibility locus on chromosome 11p11.
AB  - Susceptibility to coeliac disease has a strong genetic component. The HLA
      associations have been well described but it is clear that other genes outside
      this region must also be involved in disease development. Two previous genome
      wide linkage studies using the affected sib pair method produced conflicting
      results. Our own family based linkage study of 16 highly informative pedigrees
      identified 17 possibly linked regions, each of which produced a result
      significant at p & 0.05 or less. We have now investigated these 17 regions in a
      larger set of pedigrees using more finely spaced markers. Fifty multiply affected
      families were studied, comprising the 16 pedigrees from the original genome
      screen plus 34 new highly informative pedigrees. A total of 128 microsatellite
      markers were genotyped with an average spacing between markers of 5 cM. Two-point
      and three-point linkage analysis using classical and model free methods
      identified five potential susceptibility loci with heterogeneity lod scores >
      2.0, at 6p12, 11p11, 17q12, 18q23 and 22q13.3. The most significant was a
      heterogeneity lod of 2.6 at D11S914 on chromosome 11p11. This marker maps to a
      position implicated in one of the two previous genome scans and taken together
      these results provide strong support for the existence of a susceptibility locus
      in this region.

PMID- 11592928
TI  - Grade-of-membership sibpair linkage analysis maps IDDM11 to chromosome 14q24.3
      q31.
AB  - We demonstrate the use of Grade-of-membership (GoM) (Manton et al. 1994) for
      sibpair linkage analysis: GoM was used to map the IDDM11 locus to the region of
      chromosome 14q24.3 identified by Field et al. (1996). Haplotype groups were
      constructed from sib pair information on the number of shared alleles. The sample
      consisted of 578 sibling pairs found in 246 multiplex IDDM families. Both
      siblings were diabetic in 53% of the pairs (AA). Pair members could share 0, 1 or
      2 alleles IBS at each of eight linked marker loci spanning IDDM11. Three model
      based groups best represented the data on allele sharing: the groups corresponded
      to 'No', 'One' and 'Two' shared haplotypes for the region. Group 'Two' was larger
      (37% vs. 25%, p < 0.0001) and more homogeneous (p < 0.0001) than expected by
      chance consistent with the IDDM11 locus being a determinant of diabetes in
      multiplex families. Genetic linkage of IDDM to the region was demonstrated by a
      19% increase in the proportion of AA pairs over the haplotype groups: 'No', 42%;
      'One', 49%; 'Two', 61%, p = 0.0005, representing a 43% relative increase.

PMID- 11592930
TI  - Abstracts of the annual meeting of the International Society for Interferon and
      Cytokine Research. ISICR 2001. October 7-11, 2001. Cleveland, Ohio, USA.

PMID- 11592929
TI  - Sampling variance and distribution of the D' measure of overall gametic
      disequilibrium between multiallelic loci.
AB  - The development of the theory of estimation of gametic disequilibrium for
      multiallelic systems is particularly necessary, since a large number of the
      genetic markers available at present are highly polymorphic multiallelic systems.
      The D' coefficient is one of the most commonly used measures of the extent of
      overall disequilibrium between all possible pairs of alleles at two multiallelic
      loci. Nevertheless, the sampling properties of this measure of overall
      disequilibrium, are to date, unknown. In this work, we have derived explicit
      expressions by large-sample theory to compute the approximate sampling variance
      of Dhat' between pairs of multiallelic loci, when samples of haplotypes are taken
      from populations. Formulae for calculating the asymptotic sampling variance were
      checked by Monte Carlo simulation. In addition, the magnitude of the sampling
      variance of Dhat' was investigated under different scenarios of disequilibrium
      between multiallelic loci. Extensive simulations were also carried out for
      describing the sampling distribution of Dhat', conditioned on the sample size,
      number of alleles and their frequencies, and disequilibrium components. It was
      found that the sampling distribution of Dhat' generally approaches well the
      theoretical normal distribution for experimental sample sizes, particularly when
      loci have many alleles. Disequilibrium data between microsatellite loci of human
      chromosome 11p are used for illustration. These investigations increase
      substantially our knowledge about this widely used measure of overall
      disequilibrium, which is relevant to evaluate disequilibrium between multiallelic
      loci in populations.

PMID- 11592934
TI  - Ethics, revisited.

PMID- 11592935
TI  - Alternative splicing and diversity of renal transporters.
AB  - The growing molecular identification of renal transporter genes is revealing that
      alternative splicing is common among transporters. In this paper, I review the
      physiological consequences of alternative splicing in some genes encoding renal
      transporters in which spliced isoforms have recently been identified. In some
      cases, the spliced isoforms resulted in nonfunctional proteins, which, however,
      possess a dominant negative effect on the cotransporter function, suggesting that
      the presence of such isoforms can be important in the functional regulation of
      the transporter. In most transporter genes, however, the spliced isoforms have
      been shown to be functional, resulting in a variety of physiological
      consequences, including, for example, changes in the polarization of isoforms to
      the apical or basolateral membrane, changes in pharmacological or kinetic
      properties, and changes in tissue distribution or intrarenal localization. In
      some cases, although the spliced isoform is functional, the consequence of
      splicing is still unknown. Different regulation among isoforms is an interesting
      possibility. Thus the diversity of several renal transporters is enhanced by
      alternative splicing mechanisms.

PMID- 11592936
TI  - Targeted disruption of the bradykinin B(2) receptor gene in mice alters the
      ontogeny of the renin-angiotensin system.
AB  - Angiotensin II type 1 (AT(1)) receptor knockout (KO) mice exhibit an activated
      kallikrein-kinin system (KKS) that serves to attenuate the severity of the renal
      vascular phenotype in these mice (Tsuchida S, Miyazaki Y, Matsusaka T, Hunley TE,
      Inagami T, Fogo A, and Ichikawa I, Kidney Int 56: 509-516, 1999). Conversely,
      gestational high salt suppresses the fetal renin-angiotensin system (RAS) and
      provokes aberrant renal development in bradykinin B(2)-KO mice (El-Dahr SS,
      Harrison-Bernard LM, Dipp S, Yosipiv IV, and Meleg-Smith S, Physiol Genomics 3:
      121-131, 2000). Thus the cross talk between the RAS and KKS may be critical for
      normal renal maturation. To further define the developmental interactions between
      the KKS and RAS, we examined the consequences of B(2) receptor gene ablation on
      the expression of RAS components. Renal renin mRNA levels are 50% lower in
      newborn B(2)-KO than wild-type (WT) mice. Also, the age-related decline in renin
      mRNA is greater in B(2)-KO than WT mice (3.5- vs. 2-fold, P < 0.05). Although
      renal angiotensinogen (Ao) protein levels are higher in newborn B(2)-KO than WT
      mice, Ao mRNA levels are not, suggesting accumulation of Ao as a result of
      decreased renin-mediated cleavage. Similar age-related increases (8-fold) in
      angiotensin I-converting enzyme (ACE) activity are observed in B(2)-KO and WT
      mice. Renal AT(1) protein levels are not different in B(2)-KO and WT mice.
      Furthermore, the developmental increases in renal kallikrein mRNA and enzymatic
      activity are more pronounced in B(2)-KO compared with WT mice (mRNA: 8- vs. 3
      fold; activity: 13- vs. 6-fold, P < 0.05). We conclude that 1) bradykinin
      stimulates renin gene expression, 2) renal kallikrein is regulated via a negative
      feedback loop involving the B(2) receptor, and 3) Ao, ACE, and AT(1) are not
      bradykinin-target genes.

PMID- 11592937
TI  - Simvastatin reverses impaired regulation of renal oxygen consumption in
      congestive heart failure.
AB  - Nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS)
      regulates renal O(2) consumption. This mechanism is impaired in heart and kidney
      of dogs with heart failure (CHF). Simvastatin, an inhibitor of 3-hydroxy-3
      methylglutaryl-CoA reductase, increases eNOS expression in the endothelium.
      Therefore, we studied whether simvastatin treatment could restore the regulation
      of renal O(2) consumption by stimulators of NO production in dogs with CHF. Renal
      O(2) consumption was measured after stimulation of NO production with bradykinin,
      ramiprilat, or amlodipine or the NO donor S-nitroso-N-acetylpenicillamine (SNAP).
      Simvastatin delayed the time to euthanasia in dogs with CHF (35 +/- 1.0 vs. 29 +/
      1.2 days; P < 0.01). In normal dogs, bradykinin (10(-4) M), ramiprilat (10(-4)
      M), amlodipine (10(-5) M), and SNAP (10(-4) M) significantly reduced O(2)
      consumption in the renal cortex (-31.8 +/- 0.9, -30.3 +/- 1.1, -30.1 +/- 2.0, 
      46.9 +/- 1.0%) and renal medulla (-29.7 +/- 2.1, -33.0 +/- 2.7, -30.8 +/- 2.2, 
      46.8 +/- 1.1%). Responses to bradykinin, ramiprilat, and amlodipine were
      significantly attenuated in CHF but were partially or completely restored by
      simvastatin. Responses to SNAP were unaffected. These data demonstrate that
      treatment with simvastatin improves renal production of NO in CHF, restoring the
      normal regulation of renal O(2) consumption by NO.

PMID- 11592938
TI  - Rho-kinase regulates myosin II activation in MDCK cells during recovery after ATP
      depletion.
AB  - Alterations in the actin cytoskeleton of renal tubular epithelial cells during
      periods of ischemic injury and recovery have important consequences for normal
      cell and kidney function. Myosin II has been demonstrated to be an important
      effector in organizing basal actin structures in some cell types. ATP depletion
      in vitro has been demonstrated to recapitulate alterations of the actin
      cytoskeleton in renal tubular epithelial cells observed during renal ischemia in
      vivo. We utilized this reversible cell culture model of ischemia to examine the
      correlation of the activation state and cellular distribution of myosin II with
      disruption of actin stress fibers in Madin-Darby canine kidney (MDCK) cells
      during ATP depletion and recovery from ATP depletion. We found that myosin II
      inactivation occurs rapidly and precedes dissociation of myosin II from actin
      stress fibers during ATP depletion. Myosin II activation temporally correlates
      with colocalization of myosin II to reorganizing stress fibers during recovery
      from ATP depletion. Furthermore, myosin activation and actin stress fiber
      formation were found to be Rho-associated Ser/Thr protein kinase dependent during
      recovery from ATP depletion.

PMID- 11592939
TI  - NO decreases thick ascending limb chloride absorption by reducing Na(+)-K(+)-2Cl(
      ) cotransporter activity.
AB  - We have reported that nitric oxide (NO) inhibits thick ascending limb (THAL)
      chloride absorption (J(Cl(-))). NaCl transport in the THAL depends on apical
      Na(+)-K(+)-2Cl(-) cotransporters, apical K(+) channels, and basolateral Na(+)
      K(+)-ATPase. However, the transporter inhibited by NO is unknown. We hypothesized
      that NO decreases THAL J(Cl(-)) by inhibiting the Na(+)-K(+)-2Cl(-)
      cotransporter. THALs from Sprague-Dawley rats were isolated and perfused.
      Intracellular sodium ([Na(+)](i)) and chloride concentrations ([Cl(-)](i)) were
      measured with sodium green and SPQ, respectively. The NO donor spermine NONOate
      (SPM) decreased [Na(+)](i) from 13.5 +/- 1.2 to 9.6 +/- 1.6 mM (P < 0.05) and
      also decreased [Cl(-)](i) (P < 0.01). We next tested whether NO decreases Na(+)
      K(+)-2Cl(-) cotransporter activity by measuring the initial rate of Na(+)
      transport. In the presence of SPM in the bath, initial rates of Na(+) entry were
      49.6 +/- 6.0% slower compared with control rates (P < 0.05). To determine whether
      NO inhibits apical K(+) channel activity, we measured the change in membrane
      potential caused by an increase in luminal K(+) from 1 to 25 mM using a potential
      sensitive fluorescent dye. In the presence of SPM, increasing luminal K(+)
      concentration depolarized THALs to the same extent as it did in control tubules.
      We then tested whether a change in apical K(+) permeability could affect NO
      induced inhibition of THAL J(Cl(-)). In the presence of luminal valinomycin,
      which increases K(+) permeability, addition of SPM decreased THAL J(Cl(-)) by
      41.2 +/- 10.4%, not significantly different from the inhibition observed in
      control tubules. We finally tested whether NO alters the affinity or maximal rate
      of Na(+)-K(+)-ATPase by measuring oxygen consumption rate (QO(2)) in THAL
      suspensions in the presence of nystatin in varying concentrations of Na(+). In
      the presence of 10.5 mM Na(+), nystatin increased QO(2) to 119.1 +/- 19.2 and
      125.6 +/- 23.4 nmol O(2). mg protein(-1). min(-1) in SPM- and furosemide-treated
      tubules, respectively. In the presence of 145 mM extracellular Na(+), nystatin
      increased QO(2) by 104 +/- 7 and 94 +/- 20% in NO- and furosemide-treated
      tubules, respectively. We concluded that NO decreases THAL J(Cl(-)) by inhibiting
      Na(+)-K(+)-2Cl(-) cotransport rather than inhibiting apical K(+) channels or the
      sodium pump.

PMID- 11592941
TI  - ATP inhibits Mg(2+) uptake in MDCT cells via P2X purinoceptors.
AB  - Nucleotides have diverse effects on water and electrolyte reabsorption within the
      distal tubule of the nephron. As the distal tubule is important in control of
      renal Mg(2+) balance, we determined the effects of ATP on cellular Mg(2+) uptake
      in this segment. The effects of ATP on immortalized mouse distal convoluted
      tubule (MDCT) cells were studied by measuring Mg(2+) uptake with fluorescence
      techniques. The mean basal Mg(2+) uptake rate was 165 +/- 6 nM/s. ATP inhibited
      basal Mg(2+) uptake and hormone-stimulated Mg(2+) entry by 40%. Both P2X (P2X1
      P2X5 subtypes) and P2Y2 receptor subtypes were identified in MDCT cells using
      differential RT-PCR. Activation of both receptor subtypes with selective agonists
      increased intracellular Ca(2+) concentration, P2X purinoceptors by ionotropic
      gated channels, and P2Y receptors via G protein-mediated intracellular Ca(2+)
      release. The more relatively selective P2X agonists [beta,gamma-methylene ATP
      (beta,gamma-Me-ATP) and 2'- and -3'-O-(4-benzoyl-benzoyl)-ATP] inhibited arginine
      vasopressin (AVP)- and parathyroid hormone (PTH)-mediated Mg(2+) uptake whereas
      agonists more selective for P2Y purinoceptors (UTP, ADP, and 2-methylthio-ATP)
      were without effect. Removal of extracellular Ca(2+) diminished beta,gamma-Me-ATP
      mediated increase in intracellular Ca(2+) and inhibition of AVP-stimulated Mg(2+)
      entry. We conclude from this information that ATP inhibited Mg(2+) uptake in MDCT
      cells through P2X purinoceptors expressed in this distal convoluted tubule cell
      line.

PMID- 11592940
TI  - Adenosine A(2A) and A(2B) receptor activation of erythropoietin production.
AB  - We have examined the effects of adenosine receptors and protein kinases A and C
      in the regulation of erythropoietin (Epo) production using hepatocellular
      carcinoma (Hep3B) cells in culture and in vivo in normal mice under normoxic and
      hypoxic conditions. CGS-21680, a selective adenosine A(2A) agonist, significantly
      increased levels of Epo in normoxic Hep3B cell cultures and in serum of normal
      mice under both normoxic and hypoxic conditions. CGS-21680 also produced a
      significant increase in Epo mRNA levels in Hep3B cell cultures. SCH-58261, a
      selective adenosine A(2A) receptor antagonist, significantly inhibited the
      increase in medium levels of Epo in Hep3B cell cultures exposed to hypoxia (1%
      O(2)). Enprofylline, a selective adenosine A(2B) receptor antagonist,
      significantly inhibited the increase in plasma levels of Epo in normal mice
      exposed to hypoxia. Chelerythrine chloride, an antagonist of protein kinase C
      activation, significantly inhibited hypoxia-induced increases in serum levels of
      Epo in normal mice. A model is presented for adenosine in hypoxic regulation of
      Epo production that involves kinases A and C and phospholipase A(2) pathways.

PMID- 11592942
TI  - Complement C5b-9 induces cyclooxygenase-2 gene transcription in glomerular
      epithelial cells.
AB  - In rat membranous nephropathy, complement C5b-9 induces glomerular epithelial
      cell (GEC) injury and proteinuria, which is partially mediated by eicosanoids.
      Rat GEC in culture express cyclooxygenase (COX)-1 constitutively, whereas COX-2
      expression is induced by C5b-9. Both isoforms contribute to complement-induced
      prostaglandin generation. The present study addresses mechanisms of complement
      induced COX-2 expression in GEC. Downregulation of protein kinase C (PKC) blunted
      complement-induced upregulation of COX-2 mRNA. Complement and phorbol 12
      myristate 13-acetate (PMA) both stimulated COX-2 promoter activity. C5b-9
      activated c-Jun NH(2)-terminal kinase (JNK), and inhibition of JNK activity by
      transfection of a kinase-inactive JNK1 partially inhibited complement-induced
      (but not PMA-induced) COX-2 promoter activation. Conversely, a constitutively
      active mitogen-activated protein or extracellular signal-regulated kinase kinase
      kinase (MEKK)-1, a kinase upstream of JNK, increased COX-2 promoter activity.
      MEKK-induced COX-2 promoter activation was not affected by downregulation of PKC
      and was augmented by PMA. Thus, in GEC, PKC and JNK pathways contribute
      independently to complement-induced COX-2 expression. Nuclear factor-kappaB was
      also activated by complement in GEC but did not contribute to complement-induced
      COX-2 upregulation.

PMID- 11592943
TI  - Mechanism of heme oxygenase-1 gene induction by curcumin in human renal proximal
      tubule cells.
AB  - Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation,
      releasing iron, carbon monoxide, and biliverdin. Induction of HO-1 occurs as an
      adaptive and protective response to several inflammatory stimuli. The
      transcription factor activator protein-1 (AP-1) has been implicated in the
      activation of the HO-1 gene. To elucidate the molecular mechanism of HO-1
      induction, we examined the effects of diferuloylmethane (curcumin), an inhibitor
      of the transcription factor AP-1. Surprisingly, curcumin by itself was a very
      potent inducer of HO-1. Curcumin has anti-inflammatory, antioxidant, and
      renoprotective effects. To evaluate the mechanism of curcumin-mediated induction
      of HO-1, confluent human renal proximal tubule cells were exposed to curcumin (1
      8 microM). We observed a time- and dose-dependent induction of HO-1 mRNA that was
      associated with increased HO-1 protein. Coincubation of curcumin with actinomycin
      D completely blocked the upregulation of HO-1 mRNA. Blockade of nuclear factor
      kappaB (NF-kappaB) with an IkappaBalpha phosphorylation inhibitor attenuated
      curcumin-mediated induction of HO-1 mRNA and protein. These data demonstrate that
      curcumin induces HO-1 mRNA and protein in renal proximal tubule cells. HO-1
      induction by curcumin is mediated, at least in part, via transcriptional
      mechanisms and involves the NF-kappaB pathway.

PMID- 11592944
TI  - Effects of plasma proteins on sieving of tracer macromolecules in glomerular
      basement membrane.
AB  - It was found previously that the sieving coefficients of Ficoll and Ficoll
      sulfate across isolated glomerular basement membrane (GBM) were greatly elevated
      when BSA was present at physiological levels, and it was suggested that most of
      this increase might have been the result of steric interactions between BSA and
      the tracers (5). To test this hypothesis, we extended the theory for the sieving
      of macromolecular tracers to account for the presence of a second, abundant
      solute. Increasing the concentration of an abundant solute is predicted to
      increase the equilibrium partition coefficient of a tracer in a porous or fibrous
      membrane, thereby increasing the sieving coefficient. The magnitude of this
      partitioning effect depends on solute size and membrane structure. The osmotic
      reduction in filtrate velocity caused by an abundant, mostly retained solute will
      also tend to elevate the tracer sieving coefficient. The osmotic effect alone
      explained only about one-third of the observed increase in the sieving
      coefficients of Ficoll and Ficoll sulfate, whereas the effect of BSA on tracer
      partitioning was sufficient to account for the remainder. At physiological
      concentrations, predictions for tracer sieving in the presence of BSA were found
      to be insensitive to the assumed shape of the protein (sphere or prolate
      spheroid). For protein mixtures, the theoretical effect of 6 g/dl BSA on the
      partitioning of spherical tracers was indistinguishable from that of 3 g/dl BSA
      and 3 g/dl IgG. This suggests that for partitioning and sieving studies in vitro,
      a good experimental model for plasma is a BSA solution with a mass concentration
      matching that of total plasma protein. The effect of plasma proteins on tracer
      partitioning is expected to influence sieving not only in isolated GBM but also
      in intact glomerular capillaries in vivo.

PMID- 11592945
TI  - Bufo marinus bladder H-K-ATPase carries out electroneutral ion transport.
AB  - Bufo marinus bladder H-K-ATPase belongs to the Na-K-ATPase and H-K-ATPase
      subfamily of oligomeric P-type ATPases and is closely related to rat and human
      nongastric H-K-ATPases. It has been demonstrated that this ATPase transports K(+)
      into the cell in exchange for protons and sodium ions, but the stoichiometry of
      this cation exchange is not yet known. We studied the electrogenic properties of
      B. marinus bladder H-K-ATPase expressed in Xenopus laevis oocytes. In a HEPES
      buffered solution, K(+) activation of the H-K-ATPase induced a slow-onset inward
      current that reached an amplitude of approximately 20 nA after 1-2 min. When
      measurements were performed in a solution containing 25 mM HCO at a PCO(2) of 40
      Torr, the negative current activated by K(+) was reduced. In noninjected oocytes,
      intracellular alkalization activated an inward current similar to that due to B.
      marinus H-K-ATPase. We conclude that the transport activity of the nongastric B.
      marinus H-K-ATPase is not intrinsically electrogenic but that the inward current
      observed in oocytes expressing this ion pump is secondary to intracellular
      alkalization induced by proton transport.

PMID- 11592946
TI  - Expression of the urate transporter/channel is developmentally regulated in human
      kidneys.
AB  - Recombinant protein prepared from cDNA cloned from rat kidney and its human
      homolog function as urate transporter/channels in lipid bilayers. Using the
      antibody (anti-uricase) that detected the rat cDNA clone, we now demonstrate that
      normal human kidneys contain an immunoreactive protein of identical size to that
      in rat kidney (36-37 kDa), presumably the human urate transporter/channel (hUAT).
      The amount of hUAT in kidney homogenates increases progressively from 13 wk of
      gestation to the early postnatal period. During gestation, hUAT expression is
      confined to the cytoplasm of proximal tubules of Stage III and/or IV nephrons.
      However, at 1 yr of age hUAT is primarily located subapically and within brush
      borders of proximal tubules. Xenopus laevis oocytes and differentiated A6 cells
      injected with cRNA and transfected with cDNA of hUAT, respectively, demonstrated
      a similar pattern: hUAT is not detected in oocytes but is abundantly expressed in
      cytoplasm and plasma membranes of A6 cells. These data imply that different
      developmental factors regulate the initiation of cytoplasmic hUAT expression and
      subsequent insertion into human proximal tubule brush-border membranes.

PMID- 11592947
TI  - Renal ischemic injury results in permanent damage to peritubular capillaries and
      influences long-term function.
AB  - Acute episodes of severe renal ischemia result in acute renal failure (ARF).
      These episodes are followed by a characteristic recovery and repair response,
      whereby tubular morphology and renal function appear completely restored within
      approximately 1 mo. However, the chronic effects of such an injury have not been
      well studied. Male rats were subjected to 60-min bilateral ischemia followed by
      reperfusion, yielding a characteristic injury. Postischemic animals manifested
      severe diuresis, peaking at 1 wk postinjury (volume: >45 ml/day, ARF vs. 18
      ml/day, sham; P < 0.05). Urine flow subsequently declined but remained
      significantly elevated vs. sham animals for a 40-wk period. The prolonged
      alteration in urinary concentrating ability was attributable, in part, to a
      diminished capacity to generate a hypertonic medullary interstitium. By week 16,
      proteinuria developed in the post-ARF group and progressed for the duration of
      the study. Histological examination revealed essentially normal tubular
      morphology at 4 and 8 wk postinjury but the development of tubulointerstitial
      fibrosis at 40 wk. Transforming growth factor (TGF)-beta1 expression was elevated
      at 40 wk, but not at 4 and 8 wk postinjury. Microfil analysis revealed an
      approximately 30-50% reduction in peritubular capillary density in the inner
      stripe of the outer medulla at 4, 8, and 40 wk in post-ARF groups vs. sham
      animals. In addition, post-ARF rats manifested a significant pressor response to
      a low dose of ANG II (15 ng x kg(-1) x min(-1)). We hypothesize that severe
      ischemic injury results in a permanent alteration of renal capillary density,
      contributing to a urinary concentrating defect and the predisposition toward the
      development of renal fibrosis.

PMID- 11592948
TI  - Transcriptional regulation of heme oxygenases by HIF-1alpha in renal medullary
      interstitial cells.
AB  - The present study was designed to test the hypothesis that hypoxia-inducible
      factor-1alpha (HIF-1alpha)-mediated transcriptional activation contributes to
      increased expression of heme oxygenase (HO) genes in renal medullary interstitial
      cells (RMICs). By Northern blot analysis, HO-1 mRNA expression was found to
      significantly increase in response to reduction of PO(2) in culture medium.
      However, HO-2 mRNA was not altered by hypoxia. This hypoxia-induced upregulation
      of HO-1 mRNA was significantly blocked by HIF-1alpha inhibition with ferrous
      ammonium sulfate. To further determine the role of HIF-1alpha in the activation
      of HO-1, the inducers of HIF-1alpha were used to address whether induction of HIF
      1alpha stimulates HO-1 mRNA expression. Both desferrioxamine and CoCl(2) markedly
      increased HIF-1alpha mRNA and protein levels and resulted in the upregulation of
      HO-1 mRNA but not HO-2. Furthermore, inhibition of HIF-1alpha degradation by CBZ
      LLL, an inhibitor of ubiquitin-proteasome, significantly increased HIF-1alpha
      protein and HO-1 mRNA but not HO-2 in these cells. Using cis-element
      oligodeoxynucleotide transfection to specifically decoy HIF-1alpha and block HIF
      1alpha binding, increased mRNA expression of HO-1 in response to hypoxia and
      CoCl(2) was attenuated. In vitro nuclear run-on assays further confirmed that
      hypoxia and alterations of HIF-1alpha mRNA or protein levels significantly
      affected the formation of HO-1 mRNA. Taken together, our results indicate that HO
      1, but not HO-2, is transcriptionally activated by hypoxia through HIF-1alpha
      mediated mechanism in RMICs. This hypoxia-induced transcriptional activation may
      be one of the important mechanisms mediating increased expression of HO-1 in the
      renal medulla.

PMID- 11592949
TI  - Effects of all-trans retinoic acid on renin-angiotensin system in rats with
      experimental nephritis.
AB  - We previously demonstrated that all-trans retinoic acid (RA) preserves glomerular
      structure and function in anti-Thy1.1 nephritis (Wagner J, Dechow C, Morath C,
      Lehrke I, Amann K, Floege J, and Ritz E. J Am Soc Nephrol 11: 1479-1489, 2000).
      Because the renin-angiotensin system (RAS) contributes to renal damage, we 1)
      studied retinoid-specific effects on its components and 2) compared the effects
      of all-trans-RA with those of the AT(1)-receptor blocker candesartan. Rats were
      pretreated for 3 days before injection of the OX-7 antibody and continued with
      treatment with either vehicle or daily injections of 10 mg/kg all-trans-RA only
      (study 1) or 10 mg/kg body wt all-trans-RA, 1 mg/kg candesartan, or both (study
      2) for an additional 7 days. The blood pressure increase observed in anti-Thy1.1
      nephritic rats was equally normalized by all-trans-RA and candesartan (P < 0.05).
      In nephritic rats, mRNAs of angiotensinogen and angiotensin-converting enzyme
      (ACE) in the kidney were unchanged, but renin mRNA was lower (P < 0.01). Renal
      and glomerular AT(1)-receptor gene and protein expression levels were higher in
      anti-Thy1.1 nephritic rats (P < 0.05). In the renal cortex of nephritic rats,
      pretreatment with all-trans-RA significantly reduced mRNAs of all the examined
      RAS components, but in the glomeruli it increased ACE gene and protein expression
      (P < 0.01). In nephritic rats, candesartan reduced the number of glomerular cells
      and mitoses (P < 0.05) less efficiently than all-trans-RA (P < 0.01). Both
      substances reduced cellular proliferation (proliferating cell nuclear antigen)
      significantly (P < 0.05). No additive effects were noted when both compounds were
      combined. In conclusion, all-trans-RA influences the renal RAS in anti-Thy1.1
      nephritis by decreasing ANG II synthesis and receptor expression. The beneficial
      effect of retinoids may be explained, at least in part, by reduction of RAS
      activity.

PMID- 11592950
TI  - Immunolocalization of electrogenic sodium-bicarbonate cotransporters pNBC1 and
      kNBC1 in the rat eye.
AB  - The human NBC1 gene encodes two electrogenic sodium-bicarbonate cotransport
      proteins, pNBC1 and kNBC1, which are candidate proteins for mediating
      electrogenic sodium-bicarbonate cotransport in ocular cells. Mutations in the
      coding region of the human NBC1 gene in exons common to both pNBC1 and kNBC1
      result in a syndrome with a severe ocular and renal phenotype (blindness, band
      keratopathy, glaucoma, cataracts, and proximal renal tubular acidosis). In the
      present study, we determined the pattern of electrogenic sodium-bicarbonate
      cotransporter protein expression in rat eye. For this purpose, pNBC1- and kNBC1
      specific antibodies were generated and used to detect these NBC1 protein variants
      by immunoblotting and immunocytochemistry. pNBC1 is expressed in cornea,
      conjunctiva, lens, ciliary body, and retina, whereas the expression of kNBC1 is
      restricted to the conjunctiva. These results provide the first evidence for
      extrarenal kNBC1 protein expression. The data in this study will serve as a basis
      for understanding the molecular mechanisms responsible for abnormalities in
      ocular electrogenic sodium-bicarbonate cotransport in patients with mutations in
      the NBC1 gene.

PMID- 11592951
TI  - Autoradiographic analysis and regulation of angiotensin receptor subtypes AT(4),
      AT(1), and AT((1-7)) in the kidney.
AB  - Receptor autoradiography revealed that angiotensin AT(4) receptors were
      abundantly expressed in normal mammalian (mouse, rat, gerbil, guinea pig, rabbit)
      and avian (sparrow, chicken, turkey) kidneys and were more extensively
      distributed than previously reported (including proximal and distal segments of
      the nephron, interstitium, renal artery, vein, and ureter). Angiotensin AT(4)
      receptors were generally found to be more abundant than angiotensin AT(1)
      receptors in mammalian kidneys, whereas angiotensin AT((1-7)) receptors were not
      detected in either mammalian or avian kidneys. Rats subjected to various chronic
      treatments were found to preferentially decrease kidney AT(4) receptor density
      (furosemide, puromycin aminonucleoside, nitro-L-arginine methyl ester), decrease
      kidney AT(1) receptor density (bilateral ureteral obstruction), or increase
      kidney AT(1) receptor distribution in the inner medulla (water diuresis). These
      results indicate that the AT(4) receptor can be expressed in numerous cell types
      within the normal kidney of several species. Furthermore, several models of renal
      dysfunction and injury have been identified that selectively alter kidney AT(4)
      density and may potentially aid in elucidating the role of this novel angiotensin
      receptor system in renal function.

PMID- 11592952
TI  - Oxidative and nitrosative stress in acute renal ischemia.
AB  - Generation of reactive oxygen species and nitric oxide in hypoxia-reperfusion
      injury may form a cytotoxic metabolite, peroxynitrite, which is capable of
      causing lipid peroxidation and DNA damage. This study was designed to examine the
      contribution of oxidative and nitrosative stress to the renal damage in ischemic
      acute renal failure (iARF). iARF was initiated in rats by 45-min renal artery
      clamping. This resulted in lipid peroxidation, DNA damage, and nitrotyrosine
      modification confirmed both by Western and immunohistochemical analyses. Three
      groups of animals were randomly treated with an inhibitor of inducible nitric
      oxide synthase (NOS), L-N(6)-(1-iminoethyl)lysine (L-Nil), cell-permeable
      lecithinized superoxide dismutase (SOD), or both. Each treatment resulted in
      amelioration of renal dysfunction, as well as reduced nitrotyrosine formation,
      lipid peroxidation, and DNA damage, thus suggesting that peroxynitrite rather
      than superoxide anion is responsible for lipid peroxidation and DNA damage.
      Therefore, in a separate series of experiments, a scavenger of peroxynitrite,
      ebselen, was administered before the reperfusion period. This treatment resulted
      in a comparable degree of amelioration of iARF. In conclusion, the present study
      provides the first attempt to elucidate the role of peroxynitrite in initiation
      of the cascade of lipid peroxidation and DNA damage to ischemic kidneys. The
      results demonstrate that L-Nil, lecithinized SOD, and ebselen treatments improve
      renal function due to their suppression of peroxynitrite production or its
      scavenging, consequently preventing lipid peroxidation and oxidative DNA damage.

PMID- 11592953
TI  - AQP2 is a substrate for endogenous PP2B activity within an inner medullary AKAP
      signaling complex.
AB  - We have demonstrated that inner medullary collecting duct (IMCD) heavy endosomes
      purified from rat kidney IMCD contain the type II protein kinase A (PKA)
      regulatory subunit (RII), protein phosphatase (PP)2B, PKCzeta, and an RII-binding
      protein (relative molecular mass ~90 kDa) representing a putative A kinase
      anchoring protein (AKAP). Affinity chromatography of detergent-solubilized
      endosomes on cAMP-agarose permits recovery of a protein complex consisting of the
      90-kDa AKAP, RII, PP2B, and PKCzeta. With the use of small-particle flow
      cytometry, RII and PKCzeta were localized to an identical population of
      endosomes, suggesting that these proteins are components of an endosomal
      multiprotein complex. (32)P-labeled aquaporin-2 (AQP2) present in these PKA
      phosphorylated endosomes was dephosphorylated in vitro by either addition of
      exogenous PP2B or by an endogenous endosomal phosphatase that was inhibited by
      the PP2B inhibitors EDTA and the cyclophilin-cyclosporin A complex. We conclude
      that IMCD heavy endosomes possess an AKAP multiprotein-signaling complex similar
      to that described previously in hippocampal neurons. This signaling complex
      potentially mediates the phosphorylation of AQP2 to regulate its trafficking into
      the IMCD apical membrane. In addition, the PP2B component of the AKAP-signaling
      complex could also dephosphorylate AQP2 in vivo.

PMID- 11592954
TI  - Claudin-2 is selectively expressed in proximal nephron in mouse kidney.
AB  - The proximal nephron possesses a leaky epithelium with unique paracellular
      permeability properties that underlie its high rate of passive NaCl and water
      reabsorption, but the molecular basis is unknown. The claudins are a large family
      of transmembrane proteins that are part of the tight junction complex and likely
      form structural components of a paracellular pore. To localize claudin-2 in the
      mouse kidney, we performed in situ hybridization using an isoform-specific
      riboprobe and immunohistochemistry using a polyclonal antibody directed against a
      COOH-terminal peptide. Claudin-2 mRNA and protein were found throughout the
      proximal tubule and in the contiguous early segment of the thin descending limb
      of long-looped nephrons. The level of expression demonstrated an axial increase
      from proximal to distal segments. In confocal images, the subcellular
      localization of claudin-2 protein coincided with that of the tight junction
      protein ZO-1. Our findings suggest that claudin-2 is a component of the
      paracellular pathway of the most proximal segments of the nephron and that it may
      be responsible for their uniquely leaky permeability properties.

PMID- 11592955
TI  - Role of COX-2-derived metabolites in regulation of the renal hemodynamic response
      to norepinephrine.
AB  - The objective of this study was to examine the role of cylcooxygenase (COX)-2
      derived prostaglandins (PG) in modulating the renal hemodynamic effects of
      norepinephrine (NE) during low or normal sodium intake. The relative contribution
      of each COX isoform in producing the PG that attenuate the renal NE effects
      during normal sodium intake was also evaluated. The renal response to three doses
      of NE (50, 100, and 250 ng. kg(-1). min(-1)) was evaluated in anesthetized dogs
      pretreated with vehicle, a selective COX-2 inhibitor (nimesulide), or a
      nonselective COX inhibitor (meclofenamate). Intrarenal infusion of the two lower
      doses of NE in vehicle-pretreated dogs with normal sodium intake (n = 8) elicited
      an increase in renal vascular resistance (RVR; 21 and 34%) without inducing
      changes in glomerular filtration rate (GFR). The highest dose of NE in this group
      induced a further increment in RVR (113%) and a decrease in GFR (33%).
      Pretreatment with nimesulide in dogs with normal sodium intake (n = 7) did not
      modify the NE-induced increments in RVR but enhanced the decreases in GFR induced
      by the three NE doses (12, 26, and 64%). The renal hemodynamic response to NE in
      meclofenamate-pretreated dogs with normal sodium intake (n = 7) was similar to
      that found in dogs pretreated with nimesulide. Infusion of the lowest dose of NE
      to vehicle-pretreated dogs with low sodium intake (n = 6) did not modify GFR and
      elicited an increase in RVR (42%). Infusion of the second and third doses of NE
      led to a decrease in GFR (35 and 91%) and a rise in RVR (82 and 587%). Infusion
      of the first two doses of NE in nimesulide-pretreated dogs with low sodium intake
      (n = 5) induced a fall in GFR (64 and 92%) and an increase in RVR (174 and
      2,293%) that were greater (P < 0.05) than those induced by NE in vehicle
      pretreated dogs. The elevation in the urinary excretion rates of PGE(2) and 6
      keto-PGF(1alpha) elicited by NE was prevented in the nimesulide-pretreated dogs.
      Our results show that COX-2 inhibition potentiates the renal hemodynamic effects
      of NE and propose that the PG involved in modulating them are mainly derived from
      COX-2 activity.

PMID- 11592956
TI  - Urea and hypertonicity increase expression of heme oxygenase-1 in murine renal
      medullary cells.
AB  - Epithelial cells derived from the mammalian kidney medulla are responsive to urea
      at the levels of signal transduction and gene regulation. Hybridization of RNA
      harvested from control- and urea-treated murine inner medullary collecting duct
      (mIMCD3) cells with a cDNA expression array encoding stress-responsive genes
      suggested that heme oxygenase (HO)-1 mRNA was upregulated by urea. RNase
      protection assay confirmed this upregulation; hypertonicity also increased HO-1
      mRNA expression but neither hypertonic NaCl nor urea were effective in the
      nonrenal 3T3 cell line. The effect on HO-1 expression appeared to be
      transcriptionally mediated on the basis of mRNA half-life studies and reporter
      gene analyses using the promoters of both human and chicken HO-1. Although urea
      signaling resembles that of heavy metal signaling in other contexts, the effect
      of urea on HO-1 transcription was independent of the cadmium response element in
      this promoter. Urea-inducible HO-1 expression was sensitive to antioxidants but
      not to scavengers of nitric oxide. Urea also upregulated HO-1 protein expression
      and pharmacological inhibition of HO-1 action with zinc protoporphyrin-sensitized
      mIMCD3 cells to the adverse effects of hypertonicity but not to urea. Coupled
      with the prior observation of others that HO-1 expression increases along the
      renal corticomedullary gradient, these data suggest that HO-1 expression may
      comprise an element of the adaptive response to hypertonicity and/or urea in
      renal epithelial cells.

PMID- 11592957
TI  - Inhibition of phosphatidylinositol 4-kinase results in a significant reduced
      respiratory burst in formyl-methionyl-leucyl-phenylalanine-stimulated human
      neutrophils.
AB  - The effects of phenylarsine oxide and a monoclonal antibody directed against type
      II phosphatidylinositol 4-kinase (PI4K) on the N-formyl-methionyl-leucyl
      phenylalanine (fMLP)-stimulated respiratory burst and the PI4K activity in
      neutrophils were investigated. Fluorescence microscopic imaging showed that the
      antibody labeled with IANBD amide (N,N'-dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2
      oxa-1,3-diazol-4-yl)ethylenediamine) could enter into the cytosol possibly by
      endocytosis. It was found that the antibody inhibited the fMLP-stimulated
      respiratory burst but had little effect on the phorbol myristate acetate
      activated respiratory burst in neutrophils, whereas phenylarsine oxide inhibited
      both. It was found that even at higher concentration, the antibody could not
      completely inhibit the cell response. Using cells preincubated with human
      immunoglobulin G of the same concentration as the control, the maximal inhibition
      of the fMLP-stimulated respiratory burst by the antibody against type II PI4K was
      found to be about 70%, whereas the PI4K activity was inhibited by only about 40%.
      The discrepancy in depressing the cell response and the enzyme activity may be
      the result of depletion of the phosphatidylinositol 4,5-bisphosphate or
      phosphatidylinositol 3,4,5-trisphosphate pools during the incubation of cells
      with the antibody. Both the 40% inhibition of PI4K activity and 70% depression of
      the respiratory burst by the type II PI4K antibody may imply that at least 40% of
      the phosphatidylinositol 4,5-biphosphate was synthesized promptly by all forms of
      PI4K and phosphatidylinositol-4-phosphate 5-kinase in the fMLP-activated cells.
      The results suggest that PI4K plays a central role in either phospholipase C or
      PI3K signaling and that PI3K, PI4K, and phosphatidylinositol 4-phosphate 5-kinase
      must be considered as an integrated family for the phosphatidylinositol 3,4,5
      trisphosphate initiated signaling.

PMID- 11592958
TI  - Nitric oxide suppresses the expression of Bcl-2 binding protein BNIP3 in
      hepatocytes.
AB  - Nitric oxide (NO) is not only an important signaling molecule, but it also
      regulates the expression of a number of genes in the liver. We have previously
      shown that apoptosis in hepatocytes exposed to tumor necrosis factor-alpha and
      actinomycin D is prevented by NO derived from the inducible nitric-oxide synthase
      (iNOS), by mechanisms that are both dependent on and independent of modulation of
      cyclic guanosine monophosphate (cGMP) subsequent to activation of soluble
      guanylyl cyclase (sGC). We hypothesize that one mechanism by which NO exerts
      these effects is by regulating the expression of genes involved in apoptosis. We
      used differential display-polymerase chain reaction to isolate NO-regulated genes
      in hepatocytes from iNOS knockout mice (to eliminate endogenous inducible NO
      production). Using this analysis, we identified a NO-suppressed gene fragment
      homologous with the pro-apoptotic Bcl-2 binding protein BNIP3. Northern analysis
      confirmed the NO-dependent suppression of BNIP3 in cultured cells. Similarly, the
      NO donor S-nitroso-N-acetyl-dl-penicillamine (1-1000 microm) down-regulated the
      expression of BNIP3 in both iNOS knockout and wild-type hepatocytes. This effect
      of NO was reversed by the sGC inhibitor 1H-(1,2,4)-oxadiazole[4,3-a]quinoxalon-1
      one (ODQ),suggesting the involvement of the sGC/cGMP pathway in the modulation of
      BNIP3 by NO. We propose that suppression of BNIP3 expression is one sGC/cGMP
      dependent mechanism by which NO might affect the process of hepatocyte apoptosis.

PMID- 11592960
TI  - Regulation of GTP hydrolysis on ADP-ribosylation factor-1 at the Golgi membrane.
AB  - The interaction of the coatomer coat complex with the Golgi membrane is initiated
      by the active, GTP-bound state of the small GTPase ADP-ribosylation factor 1
      (ARF1), whereas GTP hydrolysis triggers coatomer dissociation. The hydrolysis of
      GTP on ARF1 depends on the action of members of a family of ARF1-directed GTPase
      activating proteins (GAPs). Previous studies in well defined systems indicated
      that the activity of a mammalian Golgi membrane-localized ARF GAP (GAP1) might be
      subjected to regulation by membrane lipids as well as by the coatomer complex.
      Coatomer was found to strongly stimulate GAP-dependent GTP hydrolysis on a
      membrane-independent mutant of ARF1, whereas we reported that GTP hydrolysis on
      wild type, myristoylated ARF1 loaded with GTP in the presence of phospholipid
      vesicles was coatomer-independent. To investigate the regulation of ARF1 GAPs
      under more physiological conditions, we studied GTP hydrolysis on Golgi membrane
      associated ARF1. The activities at the Golgi of recombinant GAP1 as well as
      coatomer-depleted fractions from rat brain cytosol resembled those observed in
      the presence of liposomes; however, unlike in liposomes, GAP activities on Golgi
      membranes were approximately doubled upon addition of coatomer. By contrast,
      endogenous GAP activity in Golgi membrane preparations was unaffected by
      coatomer. Cytosolic GAP activity was partially reduced following immunodepletion
      of GAP1, indicating that GAP1 plays a significant although not exclusive role in
      the regulation of GTP hydrolysis at the Golgi. Unlike the activities of the
      mammalian proteins, the Saccharomyces cerevisiae Glo3 ARF GAP displayed activity
      at the Golgi that was highly dependent on coatomer. We conclude that ARF GAPs in
      themselves can efficiently stimulate GTP hydrolysis on ARF1 at the Golgi, and
      that coatomer may play an auxiliary role in this reaction, which would lead to an
      increased cycling rate of ARF1 in COPI-coated regions of the Golgi membrane.

PMID- 11592959
TI  - Lactosylceramide is essential for the osteoclastogenesis mediated by macrophage
      colony-stimulating factor and receptor activator of nuclear factor-kappa B
      ligand.
AB  - Glycosphingolipids and their metabolites play important roles in a variety of
      biological processes. Several signal molecules are localized in a glycolipid
      enriched microdomain on the cell surface, and their signals are regulated by the
      glycolipid composition. However, the function of glycolipids in
      osteoclastogenesis has not been clearly understood. We found that D-threo-1
      phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), a glucosylceramide
      synthase inhibitor, completely inhibits the osteoclast formation induced by
      macrophage-colony-stimulating factor and receptor activator of nuclear factor
      kappa B ligand (RANKL) in a dose-dependent manner. Expression of RANK, the
      receptor of RANKL, induced by macrophage colony-stimulating factor, was reduced
      markedly in D-PDMP-treated cells. d-PDMP also inhibited the phosphorylation of
      the inhibitor of nuclear factor-kappa B and extracellular signal-regulated kinase
      1/2 induced by RANKL. In several experiments with the addition of glycolipids to
      D-PDMP-treated purified bone marrow cells, lactosylceramide (LacCer) strongly
      affected the differentiation into tartrate-resistant acid phosphatase
      mononucleated cells, but not positive multinucleated cells. GM3 and GM1 also
      recovered, but less effectively compared with LacCer. Moreover, exogenous LacCer
      recovered the reduced expression of RANK and the phosphorylation of inhibitor of
      NF-kappa B and extracellular signal-regulated kinase 1/2 after stimulation by
      RANKL at the same level of cells without D-PDMP treatment. Our data suggest that
      glycosphingolipids, especially LacCer, are necessary for the initiation step of
      RANKL-induced osteoclastogenesis.

PMID- 11592961
TI  - The immunoglobulin heavy chain locus of the duck. Genomic organization and
      expression of D, J, and C region genes.
AB  - The region of the duck IgH locus extending from upstream of the proximal
      diversity (D) segment to downstream of the constant gene cluster has been cloned
      and mapped. A sequence contig of 48,796 base pairs established that the
      organization of the genes is D-J(H)-mu-alpha-upsilon. No evidence for a
      functional homologue (or remnant) of a delta gene was found. The alpha gene is in
      inverted transcriptional orientation; class switch to IgA expression thus
      requires inversion of the approximately 27-kilobase pair region that includes
      both mu and alpha genes. The secreted forms of duck alpha and mu are each encoded
      by 4 constant region exons, and the hydrophobic C-terminal regions of the
      membrane receptor forms of alpha and mu are encoded by one and two transmembrane
      exons, respectively. Putative switch (S) regions were identified for duck mu and
      upsilon by comparison with chicken Smu and Supsilon sequences and for duck alpha
      by comparison with mouse Salpha. The duck IgH locus is rich in complex variable
      number tandem repeats, which occupy approximately 60% of the sequenced region,
      and occur at a much higher frequency in the IgH locus than in other sequenced
      regions of the duck genome.

PMID- 11592962
TI  - Transactivation of the epidermal growth factor receptor is involved in 12-O
      tetradecanoylphorbol-13-acetate-induced signal transduction.
AB  - The mechanism of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor
      promotion is still not well understood even though it is thought to be related to
      the protein kinase C/mitogen-activated protein kinase/AP-1 pathway. Recently, TPA
      was also found to induce epidermal growth factor receptor (EGFR) activity. Here,
      we investigated whether the EGFR is a necessary component for TPA-induced signal
      transduction associated with tumor promotion. We demonstrated that potent
      inhibitors of the EGFR, PD153035 and AG1478, blocked TPA-induced phosphorylation
      of extracellular signal-regulated kinases (ERKs), AP-1 activity, and cell
      transformation. Egfr gene deficiency blocked TPA-induced ERK activity and AP-1
      binding activity. The blocking of the ectodomain of the EGFR by a monoclonal
      antibody depressed TPA-induced ERK activity and AP-1 DNA binding activity. The
      use of a neutralizing antibody for heparin-binding EGF, one of the ligands of
      EGFR, blocked TPA-induced phosphorylation of ERKs. BB-94, a potent inhibitor of
      matrix metalloproteinases, which are activators of ectodomain shedding of EGFR
      ligands, also blocked TPA-induced ERK activity, AP-1 DNA binding, and cell
      transformation but had no effect on EGF-induced signal transduction. Anti-EGFR,
      anti-heparin-binding EGF, and BB-94 each blocked TPA-induced EGFR
      phosphorylation, but only anti-EGFR could block EGF-induced EGFR phosphorylation.
      Based on these results, we conclude that the EGFR is required for mediating TPA
      induced signal transduction. EGFR transactivation induced by TPA is a mechanism
      by which the EGFR mediates TPA-induced tumor promotion-related signal
      transduction.

PMID- 11592963
TI  - A conformationally sensitive residue on the cytoplasmic surface of serotonin
      transporter.
AB  - Serotonin transporter (SERT) contains a single reactive external cysteine residue
      at position 109 (Chen, J. G., Liu-Chen, S., and Rudnick, G. (1997) Biochemistry
      36, 1479-1486) and seven predicted cytoplasmic cysteines. A mutant of rat SERT
      (X8C) in which those eight cysteine residues were replaced by other amino acids
      retained approximately 32% of wild type transport activity and approximately 56%
      of wild type binding activity. In contrast to wild-type SERT or the C109A mutant,
      X8C was resistant to inhibition of high affinity cocaine analog binding by the
      cysteine reagent 2-(aminoethyl)methanethiosulfonate hydrobromide (MTSEA) in
      membrane preparations from transfected cells. Each predicted cytoplasmic cysteine
      residue was reintroduced, one at a time, into the X8C template. Reintroduction of
      Cys-357, located in the third intracellular loop, restored MTSEA sensitivity
      similar to that of C109A. Replacement of only Cys-109 and Cys-357 was sufficient
      to prevent MTSEA sensitivity. Thus, Cys-357 was the sole cytoplasmic determinant
      of MTSEA sensitivity in SERT. Both serotonin and cocaine protected SERT from
      inactivation by MTSEA at Cys-357. This protection was apparently mediated through
      a conformational change following ligand binding. Although both ligands bind in
      the absence of Na(+) and at 4 degrees C, their ability to protect Cys-357
      required Na(+) and was prevented at 4 degrees C. The accessibility of Cys-357 to
      MTSEA inactivation was increased by monovalent cations. The K(+) ion, which is
      believed to serve as a countertransport substrate for SERT, was the most
      effective ion for increasing Cys-357 reactivity.

PMID- 11592964
TI  - Potent inhibition of NFAT activation and T cell cytokine production by novel low
      molecular weight pyrazole compounds.
AB  - NFAT (nuclear factor of activated T cell) proteins are expressed in most immune
      system cells and regulate the transcription of cytokine genes critical for the
      immune response. The activity of NFAT proteins is tightly regulated by the
      Ca(2+)/calmodulin-dependent protein phosphatase 2B/calcineurin (CaN).
      Dephosphorylation of NFAT by CaN is required for NFAT nuclear localization.
      Current immunosuppressive drugs such as cyclosporin A and FK506 block CaN
      activity thus inhibiting nuclear translocation of NFAT and consequent cytokine
      gene transcription. The inhibition of CaN in cells outside of the immune system
      may contribute to the toxicities associated with cyclosporin A therapy. In a
      search for safer immunosuppressive drugs, we identified a series of 3,5
      bistrifluoromethyl pyrazole (BTP) derivatives that block Th1 and Th2 cytokine
      gene transcription. The BTP compounds block the activation-dependent nuclear
      localization of NFAT as determined by electrophoretic mobility shift assays.
      Confocal microscopy of cells expressing fluorescent-tagged NFAT confirmed that
      the BTP compounds block calcium-induced movement of NFAT from the cytosol to the
      nucleus. Inhibition of NFAT was selective because the BTP compounds did not
      affect the activation of NF-kappaB and AP-1 transcription factors. Treatment of
      intact T cells with the BTP compounds prior to calcium ionophore-induced
      activation of CaN caused NFAT to remain in a highly phosphorylated state.
      However, the BTP compounds did not directly inhibit the dephosphorylation of NFAT
      by CaN in vitro, nor did the drugs block the dephosphorylation of other CaN
      substrates including the type II regulatory subunit of protein kinase A and the
      transcription factor Elk-1. The data suggest that the BTP compounds cause NFAT to
      be maintained in the cytosol in a phosphorylated state and block the nuclear
      import of NFAT and, hence, NFAT-dependent cytokine gene transcription by a
      mechanism other than direct inhibition of CaN phosphatase activity. The novel
      inhibitors described herein will be useful in better defining the cellular
      regulation of NFAT activation and may lead to identification of new therapeutic
      targets for the treatment of autoimmune disease and transplant rejection.

PMID- 11592965
TI  - The amino-terminal domain of the vacuolar proton-translocating ATPase a subunit
      controls targeting and in vivo dissociation, and the carboxyl-terminal domain
      affects coupling of proton transport and ATP hydrolysis.
AB  - The 100-kDa "a" subunit of the vacuolar proton-translocating ATPase (V-ATPase) is
      encoded by two genes in yeast, VPH1 and STV1. The Vph1p-containing complex
      localizes to the vacuole, whereas the Stv1p-containing complex resides in some
      other intracellular compartment, suggesting that the a subunit contains
      information necessary for the correct targeting of the V-ATPase. We show that
      Stv1p localizes to a late Golgi compartment at steady state and cycles
      continuously via a prevacuolar endosome back to the Golgi. V-ATPase complexes
      containing Vph1p and Stv1p also differ in their assembly properties, coupling of
      proton transport to ATP hydrolysis, and dissociation in response to glucose
      depletion. To identify the regions of the a subunit that specify these different
      properties, chimeras were constructed containing the cytosolic amino-terminal
      domain of one isoform and the integral membrane, carboxyl-terminal domain from
      the other isoform. Like the Stv1p-containing complex, the V-ATPase complex
      containing the chimera with the amino-terminal domain of Stv1p localized to the
      Golgi and the complex did not dissociate in response to glucose depletion. Like
      the Vph1p-containing complex, the V-ATPase complex containing the chimera with
      the amino-terminal domain of Vph1p localized to the vacuole and the complex
      exhibited normal dissociation upon glucose withdrawal. Interestingly, the V
      ATPase complex containing the chimera with the carboxyl-terminal domain of Vph1p
      exhibited a higher coupling of proton transport to ATP hydrolysis than the
      chimera containing the carboxyl-terminal domain of Stv1p. Our results suggest
      that whereas targeting and in vivo dissociation are controlled by sequences
      located in the amino-terminal domains of the subunit a isoforms, coupling
      efficiency is controlled by the carboxyl-terminal region.

PMID- 11592966
TI  - Relative roles of albumin and ceruloplasmin in the formation of homocystine,
      homocysteine-cysteine-mixed disulfide, and cystine in circulation.
AB  - Disulfide forms of homocysteine account for >98% of total homocysteine in plasma
      from healthy individuals. We recently reported that homocysteine reacts with
      albumin-Cys(34)-S-S-cysteine to form homocysteine-cysteine mixed disulfide and
      albumin-Cys(34) thiolate anion. The latter then reacts with homocystine or
      homocysteine-cysteine mixed disulfide to form albumin-bound homocysteine
      (Sengupta, S., Chen, H., Togawa, T., DiBello, P. M., Majors, A. K., Budy, B.,
      Ketterer, M. E., and Jacobsen, D. W. (2001) J. Biol. Chem. 276, 30111-30117). We
      now extend these studies to show that human albumin, but not ceruloplasmin,
      mediates the conversion of homocysteine to its low molecular weight disulfide
      forms (homocystine and homocysteine-cysteine mixed disulfide) by thiol/disulfide
      exchange reactions. Only a small fraction of homocystine is formed by an
      oxidative process in which copper bound to albumin, but not ceruloplasmin,
      mediates the reaction. When copper is removed from albumin by chelation, the
      overall conversion of homocysteine to its disulfide forms is reduced by only 20%.
      Ceruloplasmin was an ineffective catalyst of homocysteine oxidation, and
      immunoprecipitation of ceruloplasmin from human plasma did not inhibit the
      capacity of plasma to mediate the conversion of homocysteine to its disulfide
      forms. In contrast, ceruloplasmin was a highly efficient catalyst for the
      oxidation of cysteine and cysteinylglycine to cystine and bis(-S
      cysteinylglycine), respectively. However, when thiols (cysteine and homocysteine)
      that are disulfide-bonded to albumin-Cys(34) are removed by treatment with
      dithiothreitol to form albumin-Cys(34)-SH (mercaptalbumin), the conversion of
      homocysteine to its disulfide forms is completely blocked. In conclusion, albumin
      mediates the formation of disulfide forms of homocysteine by thiol/disulfide
      exchange, whereas ceruloplasmin converts cysteine to cystine by copper-dependent
      autooxidation.

PMID- 11592967
TI  - The stage-regulated expression of Leishmania mexicana CPB cysteine proteases is
      mediated by an intercistronic sequence element.
AB  - The tandemly arranged CPB genes of Leishmania mexicana are polycistronically
      transcribed and encode cysteine proteases that are differentially stage-specific;
      CPB1 and CPB2 are expressed predominantly in metacyclics, whereas CPB3-CPB18 are
      expressed mainly in amastigotes. The mechanisms responsible for this differential
      expression have been studied via gene analysis and re-integration of individual
      CPB genes, and variants thereof, into a CPB-deficient parasite mutant. Comparison
      of the nucleotide sequences of the repeat units of CPB1 and CPB2 with CPB2.8
      (typical of CPB3-CPB18) revealed two major regions of divergence as follows: one
      of 258 base pairs (bp) corresponding to the C-terminal extension of CPB2.8;
      another, designated InS, of 120 bp, with insertions totaling 57 bp, localized to
      the intercistronic region downstream of CPB1 and CPB2. Cell lines expressing
      CPB2.8 or CPB2 with the 3'-untranslated region and intercistronic sequence of
      CPB2.8 showed up-regulation in amastigotes. Conversely, metacyclic-specific
      expression occurred with CPB2 or CPB2.8 with the 3'-untranslated region and
      intercistronic sequence of CPB2. Moreover, the InS down-regulated expression in
      amastigotes of a reporter gene integrated into the CPB locus. It is proposed that
      the InS mediates metacyclic-specific stage-regulated expression of CPB by
      affecting the maturation of polycistronic pre-mRNA. This is the first well
      defined cis-regulatory element implicated in post-transcriptional stage-specific
      gene expression in Leishmania.

PMID- 11592968
TI  - Curcumin, a molecule that inhibits the Ca2+-ATPase of sarcoplasmic reticulum but
      increases the rate of accumulation of Ca2+.
AB  - Curcumin, an important inhibitor of carcinogenesis, is an inhibitor of the ATPase
      activity of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum (SR).
      Inhibition by curcumin is structurally specific, requiring the presence of a pair
      of -OH groups at the 4-position of the rings. Inhibition is not competitive with
      ATP. Unexpectedly, addition of curcumin to SR vesicles leads to an increase in
      the rate of accumulation of Ca(2+), unlike other inhibitors of the Ca(2+)-ATPase
      that result in a reduced rate of accumulation. An increase in the rate of
      accumulation of Ca(2+) is seen in the presence of phosphate ion, which lowers the
      concentration of free Ca(2+) within the lumen of the SR, showing that the effect
      is not passive leak across the SR membrane. Rather, simulations suggest that the
      effect is to reduce the rate of slippage on the ATPase, a process in which a
      Ca(2+)-bound, phosphorylated intermediate releases its bound Ca(2+) on the
      cytoplasmic rather than on the lumenal side of the membrane. The structural
      specificity of the effects of curcumin on ATPase activity and on Ca(2+)
      accumulation is the same, and the apparent dissociation constants for the two
      effects are similar, suggesting that the two effects of curcumin could follow
      from binding to a single site on the ATPase.

PMID- 11592969
TI  - Structure of UDP complex of UDP-galactose:beta-galactoside-alpha -1,3
      galactosyltransferase at 1.53-A resolution reveals a conformational change in the
      catalytically important C terminus.
AB  - UDP-galactose:beta-galactosyl alpha-1,3-galactosyltransferase (alpha3GT)
      catalyzes the transfer of galactose from UDP-alpha-d-galactose into an alpha-1,3
      linkage with beta-galactosyl groups in glycoconjugates. The enzyme is expressed
      in many mammalian species but is absent from humans, apes, and old world monkeys
      as a result of the mutational inactivation of the gene; in humans, a large
      fraction of natural antibodies are directed against its product, the alpha
      galactose epitope. alpha3GT is a member of a family of metal-dependent retaining
      glycosyltransferases including the histo-blood group A and B synthases. A crystal
      structure of the catalytic domain of alpha3GT was recently reported (Gastinel, L.
      N., Bignon, C., Misra, A. K., Hindsgaul, O., Shaper, J. H., and Joziasse, D. H.
      (2001) EMBO J. 20, 638-649). However, because of the limited resolution (2.3 A)
      and high mobility of the atoms (as indicated by high B-factors) this structure
      (form I) does not provide a clear depiction of the catalytic site of the enzyme.
      Here we report a new, highly ordered structure for the catalytic domain of
      alpha3GT at 1.53-A resolution (form II). This provides a more accurate picture of
      the details of the catalytic site that includes a bound UDP molecule and a Mn(2+)
      cofactor. Significantly, in the new structure, the C-terminal segment (residues
      358-368) adopts a very different, highly structured conformation and appears to
      form part of the active site. The properties of an Arg-365 to Lys mutant indicate
      that this region is important for catalysis, possibly reflecting its role in a
      donor substrate-induced conformational change.

PMID- 11592970
TI  - The molecular interactions of heat shock protein 47 (Hsp47) and their
      implications for collagen biosynthesis.
AB  - Heat shock protein 47 (Hsp47) is a procollagen/collagen-specific molecular
      chaperone protein derived from the serpin family of proteins and essential for
      the early stages of collagen biosynthesis. In this paper, the results of an
      extensive biophysical analysis of mature recombinant mouse Hsp47 show the
      existence of both a structurally mesostable monomer with a 5-strand A-sheet
      and/or a hyperstable trimer; both states have biological activity. It is also
      demonstrated that Hsp47 is able to bind to a monomeric and partially folded
      conformation collagen mimic peptide (PPG)(10). Upon peptide binding Hsp47 has the
      capacity to induce the peptide backbone to fold into a polyproline type II
      conformation. Induction of this conformation results in (PPG)(10) peptides
      associating into higher order assemblies with increased stability compared with
      the monomeric peptide alone. These assemblies are similar to those observed by
      others (Go, N., and Suezaki, Y. (1973) Biopolymers 12, 1927-1930; Engel, J.,
      Chen, H. T., Prockop, D. J., and Klump, H. (1977) Biopolymers 16, 601-622) when
      the peptide is dissolved at high concentration and are proposed to be long chains
      of peptides in a collagen-like configuration. Examination of the biophysical
      characteristics of both monomeric and trimeric Hsp47-(PPG)(10) complexes is also
      used to determine that the peptide-binding site does not reside in strand 4
      position of sheet A, as observed for other serpins (Skinner, R., Chang, W. S. W.,
      Jin, L., Pei, X., Huntington, J. A., Abrahams, J. P., Carrell, R. W., and Lomas,
      D. A. (1998) J. Mol. Biol. 283, 9-14), leaving earlier proposals of a binding
      site near helix A viable.

PMID- 11592971
TI  - Lipoprotein sorting signals evaluated as the LolA-dependent release of
      lipoproteins from the cytoplasmic membrane of Escherichia coli.
AB  - Escherichia coli lipoproteins are anchored to either the inner or outer membrane
      through fatty acyl chains covalently attached to an N-terminal cysteine.
      Aspartate at position 2 functions to retain lipoproteins in the inner membrane,
      although the retention is perturbed depending on the residue at position 3. We
      previously revealed that LolCDE and LolA play critical roles in this lipoprotein
      sorting. To clarify the sorting signals, the LolA-dependent release of
      lipoprotein derivatives having various residues at positions 2 and 3 was examined
      in spheroplasts. When the residue at position 3 was serine, only aspartate at
      position 2 caused the retention of lipoproteins in spheroplasts. We then examined
      the release of derivatives having aspartate at position 2 and various residues at
      position 3. Strong inner membrane retention occurred with a limited number of
      species of residues at position 3. These residues were present at position 3 of
      native lipoproteins having aspartate at position 2, whereas residues that
      inhibited the retention were not. It was also found that a strong inner membrane
      retention signal having residues other than aspartate at position 2 could be
      formed through the combination of the residues at positions 2 and 3. These
      results indicate that the inner membrane localization of native lipoproteins is
      ensured by the use of a limited number of strong inner membrane retention
      signals.

PMID- 11592972
TI  - A response calculus for immobilized T cell receptor ligands.
AB  - To address the molecular mechanism of T cell receptor (TCR) signaling, we have
      formulated a model for T cell activation, termed the 2D-affinity model, in which
      the density of TCR on the T cell surface, the density of ligand on the presenting
      surface, and their corresponding two-dimensional affinity determine the level of
      T cell activation. When fitted to T cell responses against purified ligands
      immobilized on plastic surfaces, the 2D-affinity model adequately simulated
      changes in cellular activation as a result of varying ligand affinity and ligand
      density. These observations further demonstrated the importance of receptor cross
      linking density in determining TCR signaling. Moreover, it was found that the
      functional two-dimensional affinity of TCR ligands was affected by the chemical
      composition of the ligand-presenting surface. This makes it possible that cell
      bound TCR ligands, despite their low affinity in solution, are of optimal two
      dimensional affinity thereby allowing effective TCR binding under physiological
      conditions, i.e. at low ligand densities in cellular interfaces.

PMID- 11592973
TI  - Density-dependent competition and selection on immune function in genetic lizard
      morphs.
AB  - Density-dependent territorial interactions have been suggested to cause
      immunosuppression and thereby decrease fitness, but empirical support from
      natural populations is lacking. Data from a natural lizard population (Uta
      stansburiana) showed that breeding females surrounded by many territorial
      neighbors had suppressed immune function. Furthermore, variation in immunological
      condition had different effects on the fitness of the two heritable female throat
      color morphs in this population. These interactive fitness effects caused
      correlational selection between female throat color and immune responsiveness.
      Population genetic theory predicts that this should have lead to the buildup and
      preservation of a genetic correlation between female morphotype and immunological
      condition. Accordingly, the throat color of a female was genetically correlated
      (r(A) = -1.36; SE = 0.55) with her daughter's immune responsiveness.

PMID- 11592974
TI  - Plant defense in the absence of jasmonic acid: the role of cyclopentenones.
AB  - The Arabidopsis opr3 mutant is defective in the isoform of 12-oxo-phytodienoate
      (OPDA) reductase required for jasmonic acid (JA) biosynthesis. Oxylipin
      signatures of wounded opr3 leaves revealed the absence of detectable 3R,7S-JA as
      well as altered levels of its cyclopentenone precursors OPDA and dinor OPDA. In
      contrast to JA-insensitive coi1 plants and to the fad3 fad7 fad8 mutant lacking
      the fatty acid precursors of JA synthesis, opr3 plants exhibited strong
      resistance to the dipteran Bradysia impatiens and the fungus Alternaria
      brassicicola. Analysis of transcript profiles in opr3 showed the wound induction
      of genes previously known to be JA-dependent, suggesting that cyclopentenones
      could fulfill some JA roles in vivo. Treating opr3 plants with exogenous OPDA
      powerfully up-regulated several genes and disclosed two distinct downstream
      signal pathways, one through COI1, the other via an electrophile effect of the
      cyclopentenones. We conclude that the jasmonate family cyclopentenone OPDA (most
      likely together with dinor OPDA) regulates gene expression in concert with JA to
      fine-tune the expression of defense genes. More generally, resistance to insect
      and fungal attack can be observed in the absence of JA.

PMID- 11592975
TI  - A high-speed atomic force microscope for studying biological macromolecules.
AB  - The atomic force microscope (AFM) is a powerful tool for imaging individual
      biological molecules attached to a substrate and placed in aqueous solution. At
      present, however, it is limited by the speed at which it can successively record
      highly resolved images. We sought to increase markedly the scan speed of the AFM,
      so that in the future it can be used to study the dynamic behavior of
      biomolecules. For this purpose, we have developed a high-speed scanner, free of
      resonant vibrations up to 60 kHz, small cantilevers with high resonance
      frequencies (450-650 kHz) and small spring constants (150-280 pN/nm), an
      objective-lens type of deflection detection device, and several electronic
      devices of wide bandwidth. Integration of these various devices has produced an
      AFM that can capture a 100 x 100 pixel(2) image within 80 ms and therefore can
      generate a movie consisting of many successive images (80-ms intervals) of a
      sample in aqueous solution. This is demonstrated by imaging myosin V molecules
      moving on mica (see http://www.s.kanazawa-u.ac.jp/phys/biophys/bmv_movie.htm).

PMID- 11592976
TI  - Role of p42/p44 mitogen-activated-protein kinase and p21waf1/cip1 in the
      regulation of vascular smooth muscle cell proliferation by nitric oxide.
AB  - The purpose of this study was to determine the involvement of the p42/p44 mitogen
      activated protein kinase (MAPK) pathway and induction of p21(waf1/cip1) in the
      antiproliferative effects of nitric oxide (NO) on rat aortic smooth muscle cells
      (RASMC). NO, like alpha-difluoromethylornithine (DFMO), interferes with cell
      proliferation by inhibiting ornithine decarboxylase (ODC) and, therefore,
      polyamine synthesis. S-nitroso-N-acetylpenicillamine or (Z)-1-[N-(2-aminoethyl)-N
      (2-aminoethyl)-amino]-diazen-1-ium-1,2-diolate inhibited RASMC growth at
      concentrations as low as 3 microM, and DFMO elicited effects at concentrations of
      100 microM or greater. The cytostatic effect of NO and DFMO was prevented by the
      MAPK kinase 1/2 inhibitors PD 098,059 or U0126. This finding suggests that the
      p42/p44 MAPK pathway is involved in the inhibition of RASMC proliferation by NO.
      Western blot analysis revealed that treatment of RASMC with NO or DFMO leads to
      activation of p42/p44 MAPK and induction of p21(waf1/cip1). This effect was
      prevented by MAPK kinase 1/2 inhibitors, suggesting that induction of
      p21(waf1/cip1) depended on activation of p42/p44. Moreover, activation of p42/p44
      and induction of p21(waf1/cip1) were prevented by exogenous putrescine but not
      ornithine, suggesting this effect was due to the inhibition of ODC by NO or DFMO.
      Finally, activation of p42/p44 MAPK and induction of p21(waf1/cip1) were cGMP
      independent. Neither 1H-(1,2,4)oxadiazolo[4,3-alpha]quinoxalin-1-one nor
      zaprinast influenced the cytostatic effect of NO or DFMO or their ability to
      activate these signal transduction pathways. These observations suggest that
      inhibition of ODC and accompanying putrescine production are the underlying
      mechanisms by which NO and DFMO activate the MAPK pathway to promote induction of
      p21(waf1/cip1) and consequent inhibition of cell proliferation.

PMID- 11592977
TI  - TAFII55 binding to TAFII250 inhibits its acetyltransferase activity.
AB  - The general transcription factor, TFIID, consists of the TATA-binding protein
      (TBP) associated with a series of TBP-associated factors (TAFs) that together
      participate in the assembly of the transcription preinitiation complex. One of
      the TAFs, TAF(II)250, has acetyltransferase (AT) activity that is necessary for
      transcription of MHC class I genes: inhibition of the AT activity represses
      transcription. To identify potential cellular factors that might regulate the AT
      activity of TAF(II)250, a yeast two-hybrid library was screened with a TAF(II)250
      segment (amino acids 848-1279) that spanned part of its AT domain and it's the
      domain that binds to the protein, RAP74. The TFIID component, TAF(II)55, was
      isolated and found to interact predominantly with the RAP74-binding domain.
      TAF(II)55 binding to TAF(II)250 inhibits its AT activity. Importantly, the
      addition of recombinant TAF(II)55 to in vitro transcription assays inhibits
      TAF(II)250-dependent MHC class I transcription. Thus, TAF(II)55 is capable of
      regulating TAF(II)250 function by modulating its AT activity.

PMID- 11592978
TI  - Sonic hedgehog restricts adhesion and migration of neural crest cells
      independently of the Patched- Smoothened-Gli signaling pathway.
AB  - In the vertebrate embryo, neural cell types are organized spatially along the
      dorsoventral axis of the neural tube and differ by expression of cell-intrinsic
      determinants and by their adhesive and locomotory properties. Thus, dorsally,
      neural crest cells (NCC) show a strong propensity to disperse and migrate,
      whereas cells situated ventrally are highly cohesive and poorly motile. Members
      of the bone morphogenetic proteins have been shown to exert a dual role in the
      specification of dorsal neuroepithelial cells and in the dispersion of NCCs. To
      test whether Sonic hedgehog (Shh), another signaling molecule involved in the
      patterning of the ventral neural tube, might also contribute to the control of
      the adhesive and migratory potential of neuroepithelial cells, we analyzed the
      effect of ectopic Shh on NCC dispersion from neural tube explants cultured in
      vitro. The addition of Shh to the migration substrate of NCC caused inhibition of
      their dispersion. The effect of Shh on cell migration was reversible and was not
      accounted for by alterations of the specification, delamination, proliferation,
      and survival of NCCs but could be essentially attributed to a decreased cell
      substrate adhesion mediated by integrins. In addition, Shh activity on cell
      migration was mediated by a specific N-terminal region of the molecule and was
      independent from the signaling cascade elicited by the Patched-Smoothened
      receptor and involving the Gli transcription factors. Our study therefore reveals
      an unanticipated role for Shh in regulating adhesion and migration of
      neuroepithelial cells that is discernable from its inductive, mitogenic, and
      trophic functions.

PMID- 11592979
TI  - Elimination of ergovaline from a grass-Neotyphodium endophyte symbiosis by
      genetic modification of the endophyte.
AB  - The fungal endophytes Neotyphodium lolii and Neotyphodium sp. Lp1 from perennial
      ryegrass (Lolium perenne), and related endophytes in other grasses, produce the
      ergopeptine toxin ergovaline, among other alkaloids, while also increasing plant
      fitness and resistance to biotic and abiotic stress. In the related fungus,
      Claviceps purpurea, the biosynthesis of ergopeptines requires the activities of
      two peptide synthetases, LPS1 and LPS2. A peptide synthetase gene hypothesized to
      be important for ergopeptine biosynthesis was identified in C. purpurea by its
      clustering with another ergot alkaloid biosynthetic gene, dmaW. Sequence analysis
      conducted independently of the research presented here indicates that this gene
      encodes LPS1 [Tudzynski, P., Holter, K., Correia, T., Arntz, C., Grammel, N. &
      Keller, U. (1999) Mol. Gen. Genet. 261, 133-141]. We have cloned a similar
      peptide synthetase gene from Neotyphodium lolii and inactivated it by gene
      knockout in Neotyphodium sp. Lp1. The resulting strain retained full
      compatibility with its perennial ryegrass host plant as assessed by
      immunoblotting of tillers and quantitative PCR. However, grass-endophyte
      associations containing the knockout strain did not produce detectable quantities
      of ergovaline as analyzed by HPLC with fluorescence detection. Disruption of this
      gene provides a means to manipulate the accumulation of ergovaline in endophyte
      infected grasses for the purpose of determining the roles of ergovaline in
      endophyte-associated traits and, potentially, for ameliorating toxicoses in
      livestock.

PMID- 11592980
TI  - Arg-735 of the 100-kDa subunit a of the yeast V-ATPase is essential for proton
      translocation.
AB  - The vacuolar (H(+))-ATPases (V-ATPases) are ATP-dependent proton pumps that
      acidify intracellular compartments and pump protons across specialized plasma
      membranes. Proton translocation occurs through the integral V(0) domain, which
      contains five different subunits (a, d, c, c', and c"). Proton transport is
      critically dependent on buried acidic residues present in three different
      proteolipid subunits (c, c', and c"). Mutations in the 100-kDa subunit a have
      also influenced activity, but none of these residues has proven to be required
      absolutely for proton transport. On the basis of previous observations on the F
      ATPases, we have investigated the role of two highly conserved arginine residues
      present in the last two putative transmembrane segments of the yeast V-ATPase a
      subunit (Vph1p). Substitution of Asn, Glu, or Gln for Arg-735 in TM8 gives a V
      ATPase that is fully assembled but is totally devoid of proton transport and
      ATPase activity. Replacement of Arg-735 by Lys gives a V-ATPase that, although
      completely inactive for proton transport, retains 24% of wild-type ATPase
      activity, suggesting a partial uncoupling of proton transport and ATP hydrolysis
      in this mutant. By contrast, nonconservative mutations of Arg-799 in TM9 lead to
      both defective assembly of the V-ATPase complex and decreases in activity of the
      assembled V-ATPase. These results suggest that Arg-735 is absolutely required for
      proton transport by the V-ATPases and is discussed in the context of a revised
      model of the topology of the 100-kDa subunit a.

PMID- 11592981
TI  - Tsetse immune responses and trypanosome transmission: implications for the
      development of tsetse-based strategies to reduce trypanosomiasis.
AB  - Tsetse flies are the medically and agriculturally important vectors of African
      trypanosomes. Information on the molecular and biochemical nature of the
      tsetse/trypanosome interaction is lacking. Here we describe three antimicrobial
      peptide genes, attacin, defensin, and diptericin, from tsetse fat body tissue
      obtained by subtractive cloning after immune stimulation with Escherichia coli
      and trypanosomes. Differential regulation of these genes shows the tsetse immune
      system can discriminate not only between molecular signals specific for bacteria
      and trypanosome infections but also between different life stages of
      trypanosomes. The presence of trypanosomes either in the hemolymph or in the gut
      early in the infection process does not induce transcription of attacin and
      defensin significantly. After parasite establishment in the gut, however, both
      antimicrobial genes are expressed at high levels in the fat body, apparently not
      affecting the viability of parasites in the midgut. Unlike other insect immune
      systems, the antimicrobial peptide gene diptericin is constitutively expressed in
      both fat body and gut tissue of normal and immune stimulated flies, possibly
      reflecting tsetse immune responses to the multiple Gram-negative symbionts it
      naturally harbors. When flies were immune stimulated with bacteria before
      receiving a trypanosome containing bloodmeal, their ability to establish
      infections was severely blocked, indicating that up-regulation of some immune
      responsive genes early in infection can act to block parasite transmission. The
      results are discussed in relation to transgenic approaches proposed for
      modulating vector competence in tsetse.

PMID- 11592982
TI  - Correction of the retinal dystrophy phenotype of the RCS rat by viral gene
      transfer of Mertk.
AB  - The Royal College of Surgeons (RCS) rat is a widely studied animal model of
      retinal degeneration in which the inability of the retinal pigment epithelium
      (RPE) to phagocytize shed photoreceptor outer segments leads to a progressive
      loss of rod and cone photoreceptors. We recently used positional cloning to
      demonstrate that the gene Mertk likely corresponds to the retinal dystrophy (rdy)
      locus of the RCS rat. In the present study, we sought to determine whether gene
      transfer of Mertk to a RCS rat retina would result in correction of the RPE
      phagocytosis defect and preservation of photoreceptors. We used subretinal
      injection of a recombinant replication-deficient adenovirus encoding rat Mertk to
      deliver the gene to the eyes of young RCS rats. Electrophysiological assessment
      of animals 30 days after injection revealed an increased sensitivity of treated
      eyes to low-intensity light. Histologic and ultrastructural assessment
      demonstrated substantial sparing of photoreceptors, preservation of outer segment
      structure, and correction of the RPE phagocytosis defect in areas surrounding the
      injection site. Our results provide definitive evidence that mutation of Mertk
      underlies the RCS retinal dystrophy phenotype, and that the phenotype can be
      corrected by treatment of juvenile animals. To our knowledge, this is the first
      demonstration of complementation of both a functional cellular defect
      (phagocytosis) and a photoreceptor degeneration by gene transfer to the RPE.
      These results, together with the recent discovery of MERTK mutations in
      individuals with retinitis pigmentosa, emphasize the importance of the RCS rat as
      a model for gene therapy of diseases that arise from RPE dysfunction.

PMID- 11592983
TI  - Mono(ADP-ribosyl)ation of 2'-deoxyguanosine residue in DNA by an apoptosis
      inducing protein, pierisin-1, from cabbage butterfly.
AB  - Pierisin-1 is a potent apoptosis-inducing protein derived from the cabbage
      butterfly, Pieris rapae. It has been shown that pierisin-1 has an A small middle
      dotB structure-function organization like cholera or diphtheria toxin, where the
      "A" domain (N-terminal) exhibits ADP-ribosyltransferase activity. The present
      studies were designed to identify the target molecule for ADP-ribosylation by
      pierisin-1 in the presence of beta-[adenylate-(32)P]NAD, and we found DNA as the
      acceptor, but not protein as is the case with other bacteria-derived ADP
      ribosylating toxins. ADP-ribosylation of tRNAs from yeast was also catalyzed by
      pierisin-1, but the efficiency was around 110 of that for calf thymus DNA.
      Pierisin-1 efficiently catalyzed the ADP-ribosylation of double-stranded DNA
      containing dG small middle dotdC, but not dA small middle dotdT pairs. The ADP
      ribose moiety of NAD was transferred to the amino group at N(2) of 2'
      deoxyguanosine to yield N(2)-(alpha-ADP-ribos-1-yl)-2'-deoxyguanosine and its
      beta form, which were determined by several spectral analyses including (1)H- and
      (13)C-NMR and mass spectrometry. The chemical structures were also ascertained by
      the independent synthesis of N(2)-(D-ribos-1-yl)-2'-deoxyguanosine, which is the
      characteristic moiety of ADP-ribosylated dG. Using the (32)P-postlabeling method,
      ADP-ribosylated dG could be detected in DNA from pierisin-1-treated HeLa cells,
      in which apoptosis was easily induced. Thus, the targets for ADP-ribosylation by
      pierisin-1 were concluded to be 2'-deoxyguanosine residues in DNA. This finding
      may open a new field regarding the biological significance of ADP-ribosylation.

PMID- 11592984
TI  - Natural killer T cells reactive to a single glycolipid exhibit a highly diverse T
      cell receptor beta repertoire and small clone size.
AB  - CD1d-restricted natural killer (NK) T cells reactive with the glycolipid alpha
      galactosylceramide (alpha-GalCer) are a distinct lymphocyte sublineage. They
      express an invariant Valpha14-Jalpha18 T cell receptor (TcR), but the role of the
      beta chain has been controversial. Here, we have used CD1d tetramers to identify
      and isolate NK T cells based on their antigen specificity. In mice lacking
      germline Vbeta8, most of the alpha-GalCer-reactive T cells express either Vbeta2
      or Vbeta7, strong Vbeta selection being revealed by the lack of an increase in
      other Vbeta regions. By contrast to the selection for complementarity determining
      region (CDR) 3beta sequences in some anti-peptide responses, alpha-GalCer
      reactive T cells have polyclonal CDR3beta sequences. There is little CDR3beta
      sequence redundancy between organs or individual mice, and, surprisingly, there
      also is no evidence for organ-specific CDR3beta sequence motifs. These data argue
      against a T cell receptor-mediated self-reactivity for tissue-specific CD1d-bound
      ligands. Each NKT clone is represented by only 5-10 cells. This clone size is
      similar to naive conventional T cells, and much lower than that reported for
      memory T cells, although NK T cells have an activated/memory phenotype.

PMID- 11592986
TI  - Statistical equilibrium predictions of jets and spots on Jupiter.
AB  - An equilibrium statistical theory of coherent structures is applied to
      midlatitude bands in the northern and southern hemispheres of Jupiter. The theory
      imposes energy and circulation constraints on the large-scale motion and uses a
      prior distribution on potential vorticity fluctuations to parameterize the small
      scale turbulent eddies. Nonlinearly stable coherent structures are computed by
      solving the constrained maximum entropy principle governing the equilibrium
      states of the statistical theory. The theoretical predictions are consistent with
      the observed large-scale features of the weather layer if and only if the prior
      distribution has anticyclonic skewness, meaning that intense anticyclones
      predominate at small scales. Then the computations show that anticyclonic
      vortices emerge at the latitudes of the Great Red Spot and the White Ovals in the
      southern band, whereas in the northern band no vortices form within the zonal
      jets. Recent observational data from the Galileo mission support the occurrence
      of intense small-scale anticyclonic forcing. The results suggest the possibility
      of using equilibrium statistical theory for inverse modeling of the small-scale
      characteristics of the Jovian atmosphere from observed features.

PMID- 11592985
TI  - A model for gene therapy of human hereditary lymphedema.
AB  - Primary human lymphedema (Milroy's disease), characterized by a chronic and
      disfiguring swelling of the extremities, is associated with heterozygous
      inactivating missense mutations of the gene encoding vascular endothelial growth
      factor C/D receptor (VEGFR-3). Here, we describe a mouse model and a possible
      treatment for primary lymphedema. Like the human patients, the lymphedema (Chy)
      mice have an inactivating Vegfr3 mutation in their germ line, and swelling of the
      limbs because of hypoplastic cutaneous, but not visceral, lymphatic vessels.
      Neuropilin (NRP)-2 bound VEGF-C and was expressed in the visceral, but not in the
      cutaneous, lymphatic endothelia, suggesting that it may participate in the
      pathogenesis of lymphedema. By using virus-mediated VEGF-C gene therapy, we were
      able to generate functional lymphatic vessels in the lymphedema mice. Our results
      suggest that growth factor gene therapy is applicable to human lymphedema and
      provide a paradigm for other diseases associated with mutant receptors.

PMID- 11592987
TI  - Brain-specific expression of an exogenous gene after i.v. administration.
AB  - The treatment of brain diseases with gene therapy requires the gene to be
      expressed throughout the central nervous system, and this is possible by using
      gene targeting technology that delivers the gene across the blood-brain barrier
      after i.v. administration of a nonviral formulation of the gene. The plasmid DNA
      is targeted to brain with pegylated immunoliposomes (PILs) using a targeting
      ligand such as a peptidomimetic mAb, which binds to a transporting receptor on
      the blood-brain barrier. The present studies adapt the PIL gene targeting
      technology to the mouse by using the rat 8D3 mAb to the mouse transferrin
      receptor. Tissue-specific expression in brain and peripheral organs of different
      exogenous genes (beta-galactosidase, luciferase) is examined at 1-3 days after
      i.v. injection in adult mice of the exogenous gene packaged in the interior of
      8D3-PIL. The expression plasmid is driven either by a broadly expressed promoter,
      simian virus 40, or by a brain-specific promoter taken from the 5' flanking
      sequence of the human glial fibrillary acidic protein (GFAP) gene. The transgene
      is expressed in both brain and peripheral tissues when the simian virus 40
      promoter is used, but the expression of the exogenous gene is confined to the
      brain when the transgene is under the influence of the brain-specific GFAP
      promoter. Confocal microscopy colocalizes immunoreactive bacterial beta
      galactosidase with immunoreactive GFAP in brain astrocytes. These studies
      indicate that tissue-specific gene expression in brain is possible after the i.v.
      administration of a nonviral vector with the combined use of gene targeting
      technology and tissue-specific gene promoters.

PMID- 11592989
TI  - When zero is not zero: the problem of ambiguous baseline conditions in fMRI.
AB  - By using blocked and rapid event-related functional MRI studies of memory, we
      explored the implications of using rest periods as a baseline condition in
      functional MRI studies. Activity in the medial temporal lobe (as well as in other
      brain regions) was substantially higher during rest than during several
      alternative baseline conditions. The effect of this elevated activity during rest
      was to reduce, eliminate, or even reverse the sign of the activity during task
      conditions relevant to memory functions. The results demonstrate that periods of
      rest are associated with significant cognitive activity and, therefore, provide a
      nonoptimal baseline for memory tasks. These results were observed not only when
      relatively long blocks of rest were used (experiment 1), but also when rest
      consisted of the short null trials typically used in rapid event-related designs
      (experiment 2). The findings have important implications for the design and
      interpretation of a wide range of fMRI studies of cognition.

PMID- 11592988
TI  - Tetrahymena proteins p80 and p95 are not core telomerase components.
AB  - Telomeres provide stability to eukaryotic chromosomes and consist of tandem DNA
      repeat sequences. Telomeric repeats are synthesized and maintained by a
      specialized reverse transcriptase, termed telomerase. Tetrahymena thermophila
      telomerase contains two essential components: Tetrahymena telomerase reverse
      transcriptase (tTERT), the catalytic protein component, and telomerase RNA that
      provides the template for telomere repeat synthesis. In addition to these two
      components, two proteins, p80 and p95, were previously found to copurify with
      telomerase activity and to interact with tTERT and telomerase RNA. To investigate
      the role of p80 and p95 in the telomerase enzyme, we tested the interaction of
      p80, p95, and tTERT in several different recombinant expression systems and in
      Tetrahymena extracts. Immunoprecipitation of recombinant proteins showed that
      although p80 and p95 associated with each other, they did not associate with
      tTERT. In in vitro transcription and translation lysates, tTERT was associated
      with telomerase activity, but p80 and p95 were not. p80 bound telomerase RNA as
      well as several other unrelated RNAs, suggesting p80 has a general affinity for
      RNA. Immunoprecipitations from Tetrahymena extracts also showed no evidence for
      an interaction between the core tTERT/telomerase RNA complex and the p80 and p95
      proteins. These data suggest that p80 and p95 are not associated with the bulk of
      active telomerase in Tetrahymena.

PMID- 11592990
TI  - A newly discovered bacterium associated with parthenogenesis and a change in host
      selection behavior in parasitoid wasps.
AB  - The symbiotic bacterium Wolbachia pipientis has been considered unique in its
      ability to cause multiple reproductive anomalies in its arthropod hosts. Here we
      report that an undescribed bacterium is vertically transmitted and associated
      with thelytokous parthenogenetic reproduction in Encarsia, a genus of parasitoid
      wasps. Although Wolbachia was found in only one of seven parthenogenetic Encarsia
      populations examined, the "Encarsia bacterium" (EB) was found in the other six.
      Among seven sexually reproducing populations screened, EB was present in one, and
      none harbored Wolbachia. Antibiotic treatment did not induce male production in
      Encarsia pergandiella but changed the oviposition behavior of females. Cured
      females accepted one host type at the same rate as control females but
      parasitized significantly fewer of the other host type. Phylogenetic analysis
      based on the 16S rDNA gene sequence places the EB in a unique clade within the
      Cytophaga-Flexibacter-Bacteroid group and shows EB is unrelated to the
      Proteobacteria, where Wolbachia and most other insect symbionts are found. These
      results imply evolution of the induction of parthenogenesis in a lineage other
      than Wolbachia. Importantly, these results also suggest that EB may modify the
      behavior of its wasp carrier in a way that enhances its transmission.

PMID- 11592991
TI  - Segmentation gene product Fushi tarazu is an LXXLL motif-dependent coactivator
      for orphan receptor FTZ-F1.
AB  - Orphan receptors for whom cognate ligands have not yet been identified form a
      large subclass within the nuclear receptor superfamily. To address one aspect of
      how they might regulate transcription, we analyzed the mode of interaction
      between the Drosophila orphan receptor FTZ-F1 (NR5A3) and a segmentation gene
      product Fushi tarazu (FTZ). Strong interaction between these two factors was
      detected by use of the mammalian one- and two-hybrid interaction assays without
      addition of ligand. This interaction required the AF-2 core and putative ligand
      binding domain of FTZ-F1 and the LXXLL motif of FTZ. The requirement of these
      elements was further confirmed by examination of their target gene expression in
      Drosophila embryos and observation of a cuticle phenotype in transgenic fly lines
      that express mutated factors. In Drosophila cultured cells, FTZ is required for
      FTZ-F1 activation of a FTZ-F1 reporter gene. These results reveal a resemblance
      in the mode of interaction between FTZ-F1 and FTZ and that of nuclear receptor
      coactivator and indicate that direct interaction is required for regulation of
      gene expression by FTZ-F1. Thus, we propose that FTZ may represent a category of
      LXXLL motif-dependent coactivators for nuclear receptors.

PMID- 11592993
TI  - Selfish responses by clone invaders.

PMID- 11592992
TI  - Navigating the human transcriptome.

PMID- 11592994
TI  - Perceptual training: a tool for both modifying the brain and exploring it.

PMID- 11592995
TI  - Morphological properties of atmospheric aerosol aggregates.
AB  - Ultrafine particles (smaller than about 0.1 microm) are often emitted from
      combustion and other high-temperature processes in the form of fractal-like
      aggregates composed of solid nanoparticles. Results of a study of atmospheric
      aggregates are reported. Particles were collected on transmission electron
      microscope grids fitted on the last two stages of a single-jet eight-stage low
      pressure impactor for periods of a few minutes. Photomicrographs of transmission
      electron microscope grids from the impactor stages were analyzed to obtain the
      fractal dimension (D(f)) and prefactor (A) for aggregates. D(f) increased from
      near 1 to above 2 as the number of primary particles making up the aggregates
      increased from 10 to 180. Total particle concentrations in size ranges roughly
      equivalent to the low-pressure impactor stages were measured with a mobility
      analyzer and condensation particle counter. In one set of measurements, the
      fraction of the particles present as aggregates was about 60% for particles with
      aerodynamic diameters between 50 and 75 nm and 34% for the range 75 to 120 nm.
      The total aggregate concentration in the 50- to 120-nm size range was about 400
      ml(-1). The primary particles that make up atmospheric aggregates are more
      polydisperse than soot aggregates generated from a single laboratory source, an
      ethane/oxygen flame. Most measurements were made in the Los Angeles area, where
      the aggregates may represent a signature for diesel emissions. Rural aggregate
      concentrations in the size range 50 to 120 nm were less than 1% of the
      concentrations at urban sites. The data will permit better estimates of
      atmospheric aggregate residence times, transport, and deposition in the lung,
      optical extinction, and heterogeneous nucleation.

PMID- 11592996
TI  - Hierarchical self-assembly of chiral rod-like molecules as a model for peptide
      beta -sheet tapes, ribbons, fibrils, and fibers.
AB  - A generic statistical mechanical model is presented for the self-assembly of
      chiral rod-like units, such as beta-sheet-forming peptides, into helical tapes,
      which with increasing concentration associate into twisted ribbons (double
      tapes), fibrils (twisted stacks of ribbons), and fibers (entwined fibrils). The
      finite fibril width and helicity is shown to stem from a competition between the
      free energy gain from attraction between ribbons and the penalty because of
      elastic distortion of the intrinsically twisted ribbons on incorporation into a
      growing fibril. Fibers are stabilized similarly. The behavior of two rationally
      designed 11-aa residue peptides, P(11)-I and P(11)-II, is illustrative of the
      proposed scheme. P(11)-I and P(11)-II are designed to adopt the beta-strand
      conformation and to self-assemble in one dimension to form antiparallel beta
      sheet tapes, ribbons, fibrils, and fibers in well-defined solution conditions.
      The energetic parameters governing self-assembly have been estimated from the
      experimental data using the model. The 8-nm-wide fibrils consist of eight tapes,
      are extremely robust (scission energy approximately 200 k(B)T), and sufficiently
      rigid (persistence length l(fibril) approximately 20-70 microm) to form nematic
      solutions at peptide concentration c approximately 0.9 mM (volume fraction
      approximately 0.0009 vol/vol), which convert to self-supporting nematic gels at c
      > 4 mM. More generally, these observations provide a new insight into the generic
      self-assembling properties of beta-sheet-forming peptides and shed new light on
      the factors governing the structures and stability of pathological amyloid
      fibrils in vivo. The model also provides a prescription of routes to novel
      macromolecules based on a variety of self-assembling chiral units, and protocols
      for extraction of the associated energy changes.

PMID- 11592997
TI  - Femtosecond dynamics of flavoproteins: charge separation and recombination in
      riboflavine (vitamin B2)-binding protein and in glucose oxidase enzyme.
AB  - Flavoproteins can function as hydrophobic sites for vitamin B(2) (riboflavin) or,
      in other structures, with cofactors for catalytic reactions such as glucose
      oxidation. In this contribution, we report direct observation of charge
      separation and recombination in two flavoproteins: riboflavin-binding protein and
      glucose oxidase. With femtosecond resolution, we observed the ultrafast electron
      transfer from tryptophan(s) to riboflavin in the riboflavin-binding protein, with
      two reaction times: approximately 100 fs (86% component) and 700 fs (14%). The
      charge recombination was observed to take place in 8 ps, as probed by the decay
      of the charge-separated state and the recovery of the ground state. The time
      scale for charge separation and recombination indicates the local structural
      tightness for the dynamics to occur that fast and with efficiency of more than
      99%. In contrast, in glucose oxidase, electron transfer between flavin-adenine
      dinucleotide and tryptophan(s)/tyrosine(s) takes much longer times, 1.8 ps (75%)
      and 10 ps (25%); the corresponding charge recombination occurs on two time
      scales, 30 ps and nanoseconds, and the efficiency is still more than 97%. The
      contrast in time scales for the two structurally different proteins (of the same
      family) correlates with the distinction in function: hydrophobic recognition of
      the vitamin in the former requires a tightly bound structure (ultrafast
      dynamics), and oxidation-reduction reactions in the latter prefer the formation
      of a charge-separated state that lives long enough for chemistry to occur
      efficiently. Finally, we also studied the influence on the dynamics of protein
      conformations at different ionic strengths and denaturant concentrations and
      observed the sharp collapse of the hydrophobic cleft and, in contrast, the
      gradual change of glucose oxidase.

PMID- 11592998
TI  - Femtosecond dynamics of a drug-protein complex: daunomycin with Apo riboflavin
      binding protein.
AB  - In this contribution, we report studies of the primary dynamics of the drug
      protein complexes of daunomycin with apo riboflavin-binding protein. With
      femtosecond resolution, we observed the ultrafast charge separation between
      daunomycin and aromatic amino acid residues of the protein, tryptophan(s).
      Electron transfer occurs from tryptophan(s) to daunomycin with two reaction
      times, 1 ps and 6 ps, depending on the local complex structure. The formation of
      anionic daunomycin radical is crucial for triggering a series of chemical
      reactions in redox cycling. One of the subsequent reactions is the reduction of
      dioxygen to form active superoxide by the reduced daunomycin. This catalytic
      process was found to occur within 10 ps. In the absence of dioxygen, charge
      recombination takes a much longer time, more than 100 ps. These results, along
      with similar findings in DNA and nucleotides, elucidate that the ultrafast
      generation of reduced daunomycin radicals by photoactivation is a primary step
      for the observed photoenhancement of drug cytotoxicity by several orders of
      magnitude. We also studied the dependence of the dynamics on protein
      conformations at different ionic strengths and denaturant concentrations. We
      observe a sharp transition from the tertiary structure to the unfolding state at
      2 M of denaturant concentration.

PMID- 11592999
TI  - Photochemically enhanced binding of small molecules to the tumor necrosis factor
      receptor-1 inhibits the binding of TNF-alpha.
AB  - The binding of tumor necrosis factor alpha (TNF-alpha) to the type-1 TNF receptor
      (TNFRc1) plays an important role in inflammation. Despite the clinical success of
      biologics (antibodies, soluble receptors) for treating TNF-based autoimmune
      conditions, no potent small molecule antagonists have been developed. Our
      screening of chemical libraries revealed that N-alkyl 5-arylidene-2-thioxo-1,3
      thiazolidin-4-ones were antagonists of this protein-protein interaction. After
      chemical optimization, we discovered IW927, which potently disrupted the binding
      of TNF-alpha to TNFRc1 (IC(50) = 50 nM) and also blocked TNF-stimulated
      phosphorylation of Ikappa-B in Ramos cells (IC(50) = 600 nM). This compound did
      not bind detectably to the related cytokine receptors TNFRc2 or CD40, and did not
      display any cytotoxicity at concentrations as high as 100 microM. Detailed
      evaluation of this and related molecules revealed that compounds in this class
      are "photochemically enhanced" inhibitors, in that they bind reversibly to the
      TNFRc1 with weak affinity (ca. 40-100 microM) and then covalently modify the
      receptor via a photochemical reaction. We obtained a crystal structure of IV703
      (a close analog of IW927) bound to the TNFRc1. This structure clearly revealed
      that one of the aromatic rings of the inhibitor was covalently linked to the
      receptor through the main-chain nitrogen of Ala-62, a residue that has already
      been implicated in the binding of TNF-alpha to the TNFRc1. When combined with the
      fact that our inhibitors are reversible binders in light-excluded conditions, the
      results of the crystallography provide the basis for the rational design of
      nonphotoreactive inhibitors of the TNF-alpha-TNFRc1 interaction.

PMID- 11593000
TI  - Aragonite crystallization in primary cell cultures of multicellular isolates from
      a hard coral, Pocillopora damicornis.
AB  - The foundation of marine coral reef ecosystems is calcium carbonate accumulated
      primarily by the action of hard corals (Coelenterata: Anthozoa: Scleractinia).
      Colonial hard coral polyps cover the surface of the reef and deposit calcium
      carbonate as the aragonite polymorph, stabilized into a continuous calcareous
      skeleton. Scleractinian coral skeleton composition and architecture are well
      documented; however, the cellular mechanisms of calcification are poorly
      understood. There is little information on the nature of the coral cell types
      involved or their cooperation in biocalcification. We report aragonite
      crystallization in primary cell cultures of a hard coral, Pocillopora damicornis.
      Cells of apical coral colony fragments were isolated by spontaneous in vitro
      dissociation. Single dissociated cell types were separated by density in a
      discontinuous Percoll gradient. Primary cell cultures displayed a transient
      increase in alkaline phosphatase (ALP) activity, to the level observed in intact
      corals. In adherent multicellular isolate cultures, enzyme activation was
      followed by precipitation of aragonite. Modification of the ionic formulation of
      the medium prolonged maintenance of isolates, delayed ALP activation, and delayed
      aragonite precipitation. These results demonstrate that in vitro crystallization
      of aragonite in coral cell cultures is possible, and provides an innovative
      approach to investigate reef-building coral calcification at the cellular level.

PMID- 11593001
TI  - Thermodynamics of the interplay between magnetism and high-temperature
      superconductivity.
AB  - Copper-oxide-based high-temperature superconductors have complex phase diagrams
      with multiple ordered phases. It even appears that the highest superconducting
      transition temperatures for certain cuprates are found in samples that display
      simultaneous onset of magnetism and superconductivity. We show here how the
      thermodynamics of fluid mixtures-a touchstone for chemistry as well as hard and
      soft condensed matter physics-accounts for this startling observation, as well as
      many other properties of the cuprates in the vicinity of the instability toward
      "striped" magnetism.

PMID- 11593002
TI  - Nuclear envelope proteomics: novel integral membrane proteins of the inner
      nuclear membrane.
AB  - The nuclear envelope (NE) is one of the least characterized structures of
      eukaryotic cells. The study of its functional roles is hampered by the small
      number of proteins known to be specifically located to it. Here, we present a
      comprehensive characterization of the NE proteome. We applied different
      fractionation procedures and isolated protein subsets derived from distinct NE
      compartments. We identified 148 different proteins by 16-benzyl dimethyl
      hexadecyl ammonium chloride (16-BAC) gel electrophoresis and matrix-assisted
      laser desorption ionization (MALDI) mass spectrometry; among them were 19
      previously unknown or noncharacterized. The identification of known proteins in
      particular NE fractions enabled us to assign novel proteins to NE substructures.
      Thus, our subcellular proteomics approach retains the screening character of
      classical proteomic studies, but also allows a number of predictions about
      subcellular localization and interactions of previously noncharacterized
      proteins. We demonstrate this result by showing that two novel transmembrane
      proteins, a 100-kDa protein with similarity to Caenorhabditis elegans Unc-84A and
      an unrelated 45-kDa protein we named LUMA, reside in the inner nuclear membrane
      and likely interact with the nuclear lamina. The utility of our approach is not
      restricted to the investigation of the NE. Our approach should be applicable to
      the analysis of other complex membrane structures of the cell as well.

PMID- 11593003
TI  - Distinctive higher-order chromatin structure at mammalian centromeres.
AB  - The structure of the higher-order chromatin fiber has not been defined in detail.
      We have used a novel approach based on sucrose gradient centrifugation to compare
      the conformation of centromeric satellite DNA-containing higher-order chromatin
      fibers with bulk chromatin fibers obtained from the same mouse fibroblast cells.
      Our data show that chromatin fibers derived from the centromeric domain of a
      chromosome exist in a more condensed structure than bulk chromatin whereas
      pericentromeric chromatin fibers have an intermediate conformation. From the
      standpoint of current models, our data are interpreted to suggest that satellite
      chromatin adopts a regular helical conformation compatible with the canonical 30
      nm chromatin fiber whereas bulk chromatin fibers appear less regularly folded and
      are perhaps intermittently interrupted by deformations. This distinctive
      conformation of the higher-order chromatin fiber in the centromeric domain of the
      mammalian chromosome could play a role in the formation of heterochromatin and in
      the determination of centromere identity.

PMID- 11593004
TI  - Neutrophils employ the myeloperoxidase system to generate antimicrobial
      brominating and chlorinating oxidants during sepsis.
AB  - The myeloperoxidase system of neutrophils uses hydrogen peroxide and chloride to
      generate hypochlorous acid, a potent bactericidal oxidant in vitro. In a mouse
      model of polymicrobial sepsis, we observed that mice deficient in myeloperoxidase
      were more likely than wild-type mice to die from infection. Mass spectrometric
      analysis of peritoneal inflammatory fluid from septic wild-type mice detected
      elevated concentrations of 3-chlorotyrosine, a characteristic end product of the
      myeloperoxidase system. Levels of 3-chlorotyrosine did not rise in the septic
      myeloperoxidase-deficient mice. Thus, myeloperoxidase seems to protect against
      sepsis in vivo by producing halogenating species. Surprisingly, levels of 3
      bromotyrosine also were elevated in peritoneal fluid from septic wild-type mice
      and were markedly reduced in peritoneal fluid from septic myeloperoxidase
      deficient mice. Furthermore, physiologic concentrations of bromide modulated the
      bactericidal effects of myeloperoxidase in vitro. It seems, therefore, that
      myeloperoxidase can use bromide as well as chloride to produce oxidants in vivo,
      even though the extracellular concentration of bromide is at least 1,000-fold
      lower than that of chloride. Thus, myeloperoxidase plays an important role in
      host defense against bacterial pathogens, and bromide might be a previously
      unsuspected component of this system.

PMID- 11593005
TI  - Crystal structure of the central region of bovine fibrinogen (E5 fragment) at 1.4
      A resolution.
AB  - The high-resolution crystal structure of the N-terminal central region of bovine
      fibrinogen (a 35-kDa E(5) fragment) reveals a remarkable dimeric design. The two
      halves of the molecule bond together at the center in an extensive molecular
      "handshake" by using both disulfide linkages and noncovalent contacts. On one
      face of the fragment, the Aalpha and Bbeta chains from the two monomers form a
      funnel-shaped domain with an unusual hydrophobic cavity; here, on each of the two
      outer sides there appears to be a binding site for thrombin. On the opposite
      face, the N-terminal gamma chains fold into a separate domain. Despite the
      chemical identity of the two halves of fibrinogen, an unusual pair of adjacent
      disulfide bonds locally constrain the two gamma chains to adopt different
      conformations. The striking asymmetry of this domain may promote the known
      supercoiling of the protofibrils in fibrin. This information on the detailed
      topology of the E(5) fragment permits the construction of a more detailed model
      than previously possible for the critical trimolecular junction of the
      protofibril in fibrin.

PMID- 11593006
TI  - Life on carbon monoxide: X-ray structure of Rhodospirillum rubrum Ni-Fe-S carbon
      monoxide dehydrogenase.
AB  - A crystal structure of the anaerobic Ni-Fe-S carbon monoxide dehydrogenase (CODH)
      from Rhodospirillum rubrum has been determined to 2.8-A resolution. The CODH
      family, for which the R. rubrum enzyme is the prototype, catalyzes the biological
      oxidation of CO at an unusual Ni-Fe-S cluster called the C-cluster. The Ni-Fe-S C
      cluster contains a mononuclear site and a four-metal cubane. Surprisingly,
      anomalous dispersion data suggest that the mononuclear site contains Fe and not
      Ni, and the four-metal cubane has the form [NiFe(3)S(4)] and not [Fe(4)S(4)]. The
      mononuclear site and the four-metal cluster are bridged by means of Cys(531) and
      one of the sulfides of the cube. CODH is organized as a dimer with a previously
      unidentified [Fe(4)S(4)] cluster bridging the two subunits. Each monomer is
      comprised of three domains: a helical domain at the N terminus, an alpha/beta
      (Rossmann-like) domain in the middle, and an alpha/beta (Rossmann-like) domain at
      the C terminus. The helical domain contributes ligands to the bridging
      [Fe(4)S(4)] cluster and another [Fe(4)S(4)] cluster, the B-cluster, which is
      involved in electron transfer. The two Rossmann domains contribute ligands to the
      active site C-cluster. This x-ray structure provides insight into the mechanism
      of biological CO oxidation and has broader significance for the roles of Ni and
      Fe in biological systems.

PMID- 11593007
TI  - A tumor necrosis factor alpha- and interleukin 6-inducible protein that interacts
      with the small subunit of DNA polymerase delta and proliferating cell nuclear
      antigen.
AB  - A cDNA encoding a protein of 36 kDa, polymerase delta-interacting protein 1
      (PDIP1), that interacts with the small subunit (p50) of DNA polymerase delta (pol
      delta) was identified in a two-hybrid screen of a HepG2 cDNA library by using p50
      as bait. The interaction of PDIP1 with p50 was confirmed by pull-down assays, and
      a similar assay was used to demonstrate that PDIP1 interacts directly with the
      proliferating cell nuclear antigen (PCNA). PCNA and p50 bound to PDIP1
      simultaneously, and PDIP1 stimulated pol delta activity in vitro in the presence,
      but not the absence, of PCNA, suggesting that PDIP1 also interacts functionally
      with both p50 and PCNA. Subcellular localization studies demonstrated that PDIP1
      is a nuclear protein that colocalizes with PCNA at replication foci. A putative
      PCNA-binding motif was identified within the C terminus of PDIP1, and a synthetic
      peptide containing this PCNA-binding motif was shown to bind PCNA by far-Western
      analysis. Northern analysis demonstrated that PDIP1 mRNA is present in a wide
      variety of human tissues. PDIP1 was found to be highly homologous to a previously
      identified protein, B12 [Wolf, F. W., Marks, R. M., Sarma. V., Byers, M. G.,
      Katz, R. W., Shows, T. B. & Dixit, V. M. (1992) J. Biol. Chem. 267, 1317-1326],
      one of the early response genes induced by tumor necrosis factor alpha. PDIP1
      synthesis can also be induced by tumor necrosis factor alpha and by IL-6,
      cytokines essential for liver regeneration after loss of hepatic tissue. It is
      suggested that PDIP1 provides a link between cytokine activation and DNA
      replication in liver as well as in other tissues.

PMID- 11593008
TI  - Visualization of protein S1 within the 30S ribosomal subunit and its interaction
      with messenger RNA.
AB  - S1 is the largest ribosomal protein, present in the small subunit of the
      bacterial ribosome. It has a pivotal role in stabilizing the mRNA on the
      ribosome. Thus far, S1 has eluded structural determination. We have identified
      the S1 protein mass in the cryo-electron microscopic map of the Escherichia coli
      ribosome by comparing the map with a recent x-ray crystallographic structure of
      the 30S subunit, which lacks S1. According to our finding, S1 is located at the
      junction of head, platform, and main body of the 30S subunit, thus explaining all
      existing biochemical and crosslinking data. Protein S1 as identified in our map
      has a complex, elongated shape with two holes in its central portion. The N
      terminal domain, forming one of the extensions, penetrates into the head of the
      30S subunit. Evidence for direct interaction of S1 with 11 nucleotides of the
      mRNA, immediately upstream of the Shine-Dalgarno sequence, explains the protein's
      role in the recognition of the 5' region of mRNA.

PMID- 11593009
TI  - Functional analysis of mutant and wild-type Drosophila origin recognition
      complex.
AB  - The origin recognition complex (ORC) is the DNA replication initiator protein in
      eukaryotes. We have reconstituted a functional recombinant Drosophila ORC and
      compared activities of the wild-type and several mutant ORC variants. Drosophila
      ORC is an ATPase, and our studies show that the ORC1 subunit is essential for ATP
      hydrolysis and for ATP-dependent DNA binding. Moreover, DNA binding by ORC
      reduces its ATP hydrolysis activity. In vitro, ORC binds to chromatin in an ATP
      dependent manner, and this process depends on the functional AAA(+) nucleotide
      binding domain of ORC1. Mutations in the ATP-binding domain of ORC1 are unable to
      support cell-free DNA replication. However, mutations in the putative ATP-binding
      domain of either the ORC4 or ORC5 subunits do not affect either of these
      functions. We also provide evidence that the Drosophila ORC6 subunit is directly
      required for all of these activities and that a large pool of ORC6 is present in
      the cytoplasm, cytologically proximal to the cell membrane. Studies reported here
      provide the first functional dissection of a metazoan initiator and highlight the
      basic conserved and divergent features among Drosophila and budding yeast ORC
      complexes.

PMID- 11593010
TI  - Functional cloning and characterization of a UDP- glucuronic acid decarboxylase:
      the pathogenic fungus Cryptococcus neoformans elucidates UDP-xylose synthesis.
AB  - UDP-xylose is a sugar donor required for the synthesis of diverse and important
      glycan structures in animals, plants, fungi, and bacteria. Xylose-containing
      glycans are particularly abundant in plants and in the polysaccharide capsule
      that is the major virulence factor of the pathogenic fungus Cryptococcus
      neoformans. Biosynthesis of UDP-xylose is mediated by UDP-glucuronic acid
      decarboxylase, which converts UDP-glucuronic acid to UDP-xylose. Although this
      enzymatic activity was described over 40 years ago it has never been fully
      purified, and the gene encoding it has not been identified. We used homology to a
      bacterial gene, hypothesized to encode a related function, to identify a
      cryptococcal sequence as putatively encoding a UDP-glucuronic acid decarboxylase.
      A soluble 47-kDa protein derived from bacteria expressing the C. neoformans gene
      catalyzed conversion of UDP-glucuronic acid to UDP-xylose, as confirmed by NMR
      analysis. NADH, UDP, and UDP-xylose inhibit the activity. Close homologs of the
      cryptococcal gene, which we termed UXS1, appear in genome sequence data from
      organisms ranging from bacteria to humans.

PMID- 11593011
TI  - Length-dependent stability and strand length limits in antiparallel beta -sheet
      secondary structure.
AB  - Designed peptides that fold autonomously to specific conformations in aqueous
      solution are useful for elucidating protein secondary structural preferences. For
      example, autonomously folding model systems have been essential for establishing
      the relationship between alpha-helix length and alpha-helix stability, which
      would be impossible to probe with alpha-helices embedded in folded proteins.
      Here, we use designed peptides to examine the effect of strand length on
      antiparallel beta-sheet stability. alpha-Helices become more stable as they grow
      longer. Our data show that a two-stranded beta-sheet ("beta-hairpin") becomes
      more stable when the strands are lengthened from five to seven residues, but that
      further strand lengthening to nine residues does not lead to further beta-hairpin
      stabilization for several extension sequences examined. (In one case, all
      threonine extension, there may be an additional stabilization on strand
      lengthening from seven to nine residues.) These results suggest that there may be
      an intrinsic limit to strand length for most sequences in antiparallel beta-sheet
      secondary structure.

PMID- 11593012
TI  - High intranuclear mobility and dynamic clustering of the splicing factor U1 snRNP
      observed by single particle tracking.
AB  - Uridine-rich small nuclear ribonucleoproteins (U snRNPs) are components of the
      splicing machinery that removes introns from precursor mRNA. Like other splicing
      factors, U snRNPs are diffusely distributed throughout the nucleus and, in
      addition, are concentrated in distinct nuclear substructures referred to as
      speckles. We have examined the intranuclear distribution and mobility of the
      splicing factor U1 snRNP on a single-molecule level. Isolated U1 snRNPs were
      fluorescently labeled and incubated with digitonin-permeabilized 3T3 cells in the
      presence of Xenopus egg extract. By confocal microscopy, U1 snRNPs were found to
      be imported into nuclei, yielding a speckled intranuclear distribution. Employing
      a laser video-microscope optimized for high sensitivity and high speed, single U1
      snRNPs were visualized and tracked at a spatial precision of 35 nm and a time
      resolution of 30 ms. The single-particle data revealed that U1 snRNPs occurred in
      small clusters that colocalized with speckles. In the clusters, U1 snRNPs resided
      for a mean decay time of 84 ms before leaving the optical slice in the direction
      of the optical axis, which corresponded to a mean effective diffusion coefficient
      of 1 microm(2)/s. An analysis of the trajectories of single U1 snRNPs revealed
      that at least three kinetic classes of low, medium, and high mobility were
      present. Moreover, the mean square displacements of these fractions were
      virtually independent of time, suggesting arrays of binding sites. The results
      substantiate the view that nuclear speckles are not rigid structures but highly
      dynamic domains characterized by a rapid turnover of U1 snRNPs and other splicing
      factors.

PMID- 11593013
TI  - Inactivation of the endoplasmic reticulum protein translocation factor, Sec61p,
      or its homolog, Ssh1p, does not affect peroxisome biogenesis.
AB  - Peroxisomes are single membrane-bound organelles present in virtually all
      eukaryotes. These organelles participate in several important metabolic
      processes, and defects in peroxisome function and biogenesis are a significant
      contributor to human disease. Several models propose that peroxisomes arise from
      the endoplasmic reticulum (ER) in a process that involves the translocation of
      "group I" peroxisomal membrane proteins into the ER, the exit of these group I
      peroxisomal membrane proteins from the ER by vesicle budding, and the formation
      of nascent peroxisomes from vesicles containing the group I peroxisomal membrane
      proteins. A central prediction of these models is that the formation of nascent
      peroxisomes requires protein translocation into the ER. Sec61p is an essential
      component of the ER translocon, and we show here that loss of Sec61p activity has
      no effect on peroxisome biogenesis. In addition, loss of the SEC61-related gene,
      SSH1, also has no effect on peroxisome biogenesis. Although some proteins may
      enter the ER independently of Sec61p or Ssh1p, none are known, leading us to
      propose that peroxisome biogenesis may not require protein import into the ER,
      and by extension, transfer of proteins from the ER to the peroxisome.

PMID- 11593014
TI  - The human decatenation checkpoint.
AB  - Chromatid catenation is actively monitored in human cells, with progression from
      G(2) to mitosis being inhibited when chromatids are insufficiently decatenated.
      Mitotic delay was quantified in normal and checkpoint-deficient human cells
      during treatment with ICRF-193, a topoisomerase II catalytic inhibitor that
      prevents chromatid decatenation without producing topoisomerase-associated DNA
      strand breaks. Ataxia telangiectasia (A-T) cells, defective in DNA damage
      checkpoints, showed normal mitotic delay when treated with ICRF-193. The mitotic
      delay in response to ICRF-193 was ablated in human fibroblasts expressing an
      ataxia telangiectasia mutated- and rad3-related (ATR) kinase-inactive ATR allele
      (ATR(ki)). BRCA1-mutant HCC1937 cells also displayed a defect in ICRF-193-induced
      mitotic delay, which was corrected by expression of wild-type BRCA1.
      Phosphorylations of hCds1 or Chk1 and inhibition of Cdk1 kinase activity, which
      are elements of checkpoints associated with DNA damage or replication, did not
      occur during ICRF-193-induced mitotic delay. Over-expression of cyclin B1
      containing a dominant nuclear localization signal, and inhibition of Crm1
      mediated nuclear export, reversed ICRF-193-induced mitotic delay. In combination,
      these results imply that ATR and BRCA1 enforce the decatenation G(2) checkpoint,
      which may act to exclude cyclin B1/Cdk1 complexes from the nucleus. Moreover,
      induction of ATR(ki) produced a 10-fold increase in chromosomal aberrations,
      further emphasizing the vital role for ATR in genetic stability.

PMID- 11593015
TI  - Lipid rafts are required for GLUT4 internalization in adipose cells.
AB  - It has been recently reported that insulin recruits a novel signaling machinery
      to lipid rafts required for insulin-stimulated GLUT4 translocation [Baumann, A.,
      Ribon, V., Kanzaki, M., Thurmond, D. C., Mora, S., Shigematsu, S., Bickel, P. E.,
      Pessin, J. E. & Saltiel, A. R. (2001) Nature 407, 202-207, 2000; Chiang, S. H.,
      Baumann, C. A., Kanzaki, M., Thurmond, D. C., Watson, R. T., Neudauer, C. L.,
      Macara, I. G., Pessin, J. E. & Saltiel, A. R. (2001) Nature 410, 944-948]. We
      have assessed the role of lipid rafts on GLUT4 traffic in adipose cells. High
      GLUT4 levels were detected in caveolae from adipocytes by two approaches, the
      mechanical isolation of purified caveolae from plasma membrane lawns and the
      immunogold analysis of plasma membrane lawns followed by freeze-drying. The role
      of lipid rafts in GLUT4 trafficking was studied by adding nystatin or filipin at
      concentrations that specifically disrupt caveolae morphology and inhibit caveolae
      function without altering clathrin-mediated endocytosis. These caveolae
      inhibitors did not affect the insulin-stimulated glucose transport. However, they
      blocked both the GLUT4 internalization and the down-regulation of glucose
      transport triggered by insulin removal in 3T3-L1 adipocytes. Our data indicate
      that lipid rafts are crucial for GLUT4 internalization after insulin removal.
      Given that high levels of GLUT4 were detected in caveolae from insulin-treated
      adipose cells, this transporter may be internalized from caveolae or caveolae may
      operate as an obligatory transition station before internalization.

PMID- 11593016
TI  - Proteomic method identifies proteins nitrated in vivo during inflammatory
      challenge.
AB  - Inflammation in asthma, sepsis, transplant rejection, and many neurodegenerative
      diseases associates an up-regulation of NO synthesis with increased protein
      nitration at tyrosine. Nitration can cause protein dysfunction and is implicated
      in pathogenesis, but few proteins that appear nitrated in vivo have been
      identified. To understand how this modification impacts physiology and disease,
      we used a proteomic approach toward targets of protein nitration in both in vivo
      and cell culture inflammatory disease models. This approach identified more than
      40 nitrotyrosine-immunopositive proteins, including 30 not previously identified,
      that became modified as a consequence of the inflammatory response. These targets
      include proteins involved in oxidative stress, apoptosis, ATP production, and
      other metabolic functions. Our approach provides a means toward obtaining a
      comprehensive view of the nitroproteome and promises to broaden understanding of
      how NO regulates cellular processes.

PMID- 11593017
TI  - Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link
      between cancer and aging.
AB  - Mammalian cells can respond to damage or stress by entering a state of arrested
      growth and altered function termed cellular senescence. Several lines of evidence
      suggest that the senescence response suppresses tumorigenesis. Cellular
      senescence is also thought to contribute to aging, but the mechanism is not well
      understood. We show that senescent human fibroblasts stimulate premalignant and
      malignant, but not normal, epithelial cells to proliferate in culture and form
      tumors in mice. In culture, the growth stimulation was evident when senescent
      cells comprised only 10% of the fibroblast population and was equally robust
      whether senescence was induced by replicative exhaustion, oncogenic RAS,
      p14(ARF), or hydrogen peroxide. Moreover, it was due at least in part to soluble
      and insoluble factors secreted by senescent cells. In mice, senescent, much more
      than presenescent, fibroblasts caused premalignant and malignant epithelial cells
      to form tumors. Our findings suggest that, although cellular senescence
      suppresses tumorigenesis early in life, it may promote cancer in aged organisms,
      suggesting it is an example of evolutionary antagonistic pleiotropy.

PMID- 11593018
TI  - Functional communication between endogenous BRCA1 and its partner, BARD1, during
      Xenopus laevis development.
AB  - The breast and ovarian susceptibility protein 1 (BRCA1) heterodimerizes with its
      structural relative, the BRCA1-associated RING domain protein (BARD1), which may
      have tumor suppressing function in its own right. Both proteins have evolved from
      a common evolutionary ancestor, and both exist in Xenopus laevis where, similar
      to their mammalian homologs, they form functional heterodimers. Depleting frog
      embryos of either BARD1 or BRCA1 led to similar and widely defective
      developmental phenotypes as well as depletion of the other polypeptide due to its
      decreased stability. Thus, each protein, in part, controls the abundance,
      stability, and function of the other, and these effects are heterodimerization
      dependent. The interdependent nature of BRCA1 and BARD1 function supports the
      view that BARD1/BRCA1 heterodimers play a major role in breast and ovarian cancer
      suppression.

PMID- 11593019
TI  - Chromosomal inversions and the reproductive isolation of species.
AB  - Recent genetic studies have suggested that many genes contribute to differences
      between closely related species that prevent gene exchange, particularly hybrid
      male sterility and female species preferences. We have examined the genetic basis
      of hybrid sterility and female species preferences in Drosophila pseudoobscura
      and Drosophila persimilis, two occasionally hybridizing North American species.
      Contrary to findings in other species groups, very few regions of the genome were
      associated with these characters, and these regions are associated also with
      fixed arrangement differences (inversions) between these species. From our
      results, we propose a preliminary genic model whereby inversions may contribute
      to the speciation process, thereby explaining the abundance of arrangement
      differences between closely related species that co-occur geographically. We
      suggest that inversions create linkage groups that cause sterility to persist
      between hybridizing taxa. The maintenance of this sterility allows the species to
      persist in the face of gene flow longer than without such inversions, and natural
      selection will have a greater opportunity to decrease the frequency of
      interspecies matings.

PMID- 11593020
TI  - Multidimensional epistasis and the disadvantage of sex.
AB  - Sex is thought to facilitate accumulation of initially rare beneficial mutations
      by allowing simultaneous allele replacements at many loci. However, this
      advantage of sex depends on a restrictive assumption that the fitness of a
      genotype is determined by fitness potential, a single intermediate variable to
      which all loci contribute additively, so that new alleles can accumulate in any
      order. Individual-based simulations of sexual and asexual populations reveal that
      under generic selection, sex often retards adaptive evolution. When new alleles
      are beneficial only if they accumulate in a prescribed order, a sexual population
      may evolve two or more times slower than an asexual population because only
      asexual reproduction allows some overlap of successive allele replacements. Many
      other fitness surfaces lead to an even greater disadvantage of sex. Thus, either
      sex exists in spite of its impact on the rate of adaptive allele replacements, or
      natural fitness surfaces have rather specific properties, at least at the scale
      of intrapopulation genetic variability.

PMID- 11593021
TI  - Quantitative mutant analysis of viral quasispecies by chip-based matrix-assisted
      laser desorption/ ionization time-of-flight mass spectrometry.
AB  - RNA viruses exist as quasispecies, heterogeneous and dynamic mixtures of mutants
      having one or more consensus sequences. An adequate description of the genomic
      structure of such viral populations must include the consensus sequence(s) plus a
      quantitative assessment of sequence heterogeneities. For example, in quality
      control of live attenuated viral vaccines, the presence of even small quantities
      of mutants or revertants may indicate incomplete or unstable attenuation that may
      influence vaccine safety. Previously, we demonstrated the monitoring of oral
      poliovirus vaccine with the use of mutant analysis by PCR and restriction enzyme
      cleavage (MAPREC). In this report, we investigate genetic variation in live
      attenuated mumps virus vaccine by using both MAPREC and a platform (DNA
      MassArray) based on matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF) mass spectrometry. Mumps vaccines prepared from the Jeryl Lynn strain
      typically contain at least two distinct viral substrains, JL1 and JL2, which have
      been characterized by full length sequencing. We report the development of assays
      for characterizing sequence variants in these substrains and demonstrate their
      use in quantitative analysis of substrains and sequence variations in mixed virus
      cultures and mumps vaccines. The results obtained from both the MAPREC and MALDI
      TOF methods showed excellent correlation. This suggests the potential utility of
      MALDI-TOF for routine quality control of live viral vaccines and for assessment
      of genetic stability and quantitative monitoring of genetic changes in other RNA
      viruses of clinical interest.

PMID- 11593022
TI  - The contribution of 700,000 ORF sequence tags to the definition of the human
      transcriptome.
AB  - Open reading frame expressed sequences tags (ORESTES) differ from conventional
      ESTs by providing sequence data from the central protein coding portion of
      transcripts. We generated a total of 696,745 ORESTES sequences from 24 human
      tissues and used a subset of the data that correspond to a set of 15,095 full
      length mRNAs as a means of assessing the efficiency of the strategy and its
      potential contribution to the definition of the human transcriptome. We estimate
      that ORESTES sampled over 80% of all highly and moderately expressed, and between
      40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced
      tissue, the breast, the 130,000 ORESTES generated are derived from transcripts
      from an estimated 70% of all genes expressed in that tissue, with an equally
      efficient representation of both highly and poorly expressed genes. In this
      respect, we find that the capacity of the ORESTES strategy both for gene
      discovery and shotgun transcript sequence generation significantly exceeds that
      of conventional ESTs. The distribution of ORESTES is such that many human
      transcripts are now represented by a scaffold of partial sequences distributed
      along the length of each gene product. The experimental joining of the scaffold
      components, by reverse transcription-PCR, represents a direct route to transcript
      finishing that may represent a useful alternative to full-length cDNA cloning.

PMID- 11593023
TI  - DNA ligase IV-deficient cells are more resistant to ionizing radiation in the
      absence of Ku70: Implications for DNA double-strand break repair.
AB  - Vertebrate cells have evolved two major pathways for repairing DNA double-strand
      breaks (DSBs), homologous recombination (HR) and nonhomologous DNA end-joining
      (NHEJ). To investigate the role of DNA ligase IV (Lig4) in DSB repair, we knocked
      out the Lig4 gene (LIG4) in the DT40 chicken B-lymphocyte cell line. The LIG4(-/
      ) cells showed a marked sensitivity to X-rays, bleomycin, and VP-16 and were more
      x-ray-sensitive in G(1) than late S or G(2)/M, suggesting a critical role of Lig4
      in DSB repair by NHEJ. In support of this notion, HR was not impaired in LIG4(-/
      ) cells. LIG4(-/-) cells were more x-ray-sensitive when compared with KU70(-/-)
      DT40 cells, particularly at high doses. Strikingly, however, the x-ray
      sensitivity of KU70(-/-)/LIG4(-/-) double-mutant cells was essentially the same
      as that of KU70(-/-) cells, showing that Lig4 deficiency has no effect in the
      absence of Ku. These results indicate that Lig4 is exclusively required for the
      Ku-dependent NHEJ pathway of DSB repair and that other DNA ligases (I and III) do
      not substitute for this function. Our data may explain the observed severe
      phenotype of Lig4-deficient mice as compared with Ku-deficient mice.

PMID- 11593024
TI  - Identification of a conserved erythroid specific domain of histone acetylation
      across the alpha-globin gene cluster.
AB  - We have analyzed the pattern of core histone acetylation across 250 kb of the
      telomeric region of the short arm of human chromosome 16. This gene-dense region,
      which includes the alpha-globin genes and their regulatory elements embedded
      within widely expressed genes, shows marked differences in histone acetylation
      between erythroid and non-erythroid cells. In non-erythroid cells, there was a
      uniform 2- to 3-fold enrichment of acetylated histones, compared with
      heterochromatin, across the entire region. In erythroid cells, an approximately
      100-kb segment of chromatin encompassing the alpha genes and their remote major
      regulatory element was highly enriched in histone H4 acetylated at Lys-5. Other
      lysines in the N-terminal tail of histone H4 showed intermediate and variable
      levels of enrichment. Similar broad segments of erythroid-specific histone
      acetylation were found in the corresponding syntenic regions containing the mouse
      and chicken alpha-globin gene clusters. The borders of these regions of
      acetylation are located in similar positions in all three species, and a sharply
      defined 3' boundary coincides with the previously identified breakpoint in
      conserved synteny between these species. We have therefore demonstrated that an
      erythroid-specific domain of acetylation has been conserved across several
      species, encompassing not only the alpha-globin genes but also a neighboring
      widely expressed gene. These results contrast with those at other clusters and
      demonstrate that not all genes are organized into discrete regulatory domains.

PMID- 11593025
TI  - Nuclear relocation of a transactivator subunit precedes target gene activation.
AB  - Murine erythroleukemia (MEL) cells are a model system to study reorganization of
      the eukaryotic nucleus during terminal differentiation. Upon chemical induction,
      MEL cells undergo erythroid differentiation, leading to activation of globin gene
      expression. Both processes strongly depend on the transcriptional activator NF
      E2. Before induction of differentiation, both subunits of the NF-E2 heterodimer
      are present, but little DNA-binding activity is detectable. Using
      immunofluorescence microscopy, we show that the two NF-E2 subunits occupy
      distinct nuclear compartments in uninduced MEL cells; the smaller subunit NF
      E2p18 is found primarily in the centromeric heterochromatin compartment, whereas
      the larger subunit NF-E2p45 occupies the euchromatin compartment. Concomitant
      with the commitment period of differentiation that precedes globin gene
      activation, NF-E2p18, along with other transcriptional repressors, relocates to
      the euchromatin compartment. Thus, relocation of NF-E2 p18 may be a rate-limiting
      step in formation of an active NF-E2 complex. To understand the mechanisms of NF
      E2 localization, we show that centromeric targeting of NF-E2p18 requires
      dimerization, but not with an erythroid-specific partner, and that the
      transactivation domain of NF-E2p45 may be necessary and sufficient to prevent its
      localization in centromeric heterochromatin. Finally, using fluorescence in situ
      hybridization, we show that, upon differentiation, the beta-globin gene loci
      relocate away from heterochromatin compartments to euchromatin. This relocation
      correlates with both transcriptional activation of the globin locus and
      relocation of NF-E2p18 away from heterochromatin, suggesting that these processes
      are linked.

PMID- 11593026
TI  - The maternal effect gene, abnormal oocyte (abo), of Drosophila melanogaster
      encodes a specific negative regulator of histones.
AB  - The abnormal oocyte (abo) gene of Drosophila melanogaster is a peculiar maternal
      effect gene whose mutations cause a maternal-effect lethality that can be rescued
      by specific regions of heterochromatin during early embryogenesis. Here we show
      that abo encodes an evolutionary conserved chromosomal protein that localizes
      exclusively to the histone gene cluster and binds to the regulatory regions of
      such genes. We also show a significant increase of histone transcripts in eggs of
      abo mutant mothers and a partial rescue of the abo maternal-effect defect by
      deficiencies of the histone gene cluster. On the basis of these results, we
      suggest that the Abo protein functions specifically as a negative regulator of
      histone transcription and propose a molecular model to account for the ability of
      heterochromatin to partially rescue the abo maternal-effect defect. Our model
      proposes that increased doses of specific heterochromatic regions titrate out
      abnormally high levels of histones present in embryos from mutant abo mothers and
      that a balanced pool of histones is critical for normal embryogenesis in
      Drosophila.

PMID- 11593027
TI  - The role of binding domains for dsRNA and Z-DNA in the in vivo editing of minimal
      substrates by ADAR1.
AB  - RNA editing changes the read-out of genetic information, increasing the number of
      different protein products that can be made from a single gene. One form involves
      the deamination of adenosine to form inosine, which is subsequently translated as
      guanosine. The reaction requires a double-stranded RNA (dsRNA) substrate and is
      catalyzed by the adenosine deaminase that act on dsRNA (ADAR) family of enzymes.
      These enzymes possess dsRNA-binding domains (DRBM) and a catalytic domain. ADAR1
      so far has been found only in vertebrates and is characterized by two Z-DNA
      binding motifs, the biological function of which remains unknown. Here the role
      of the various functional domains of ADAR1 in determining the editing efficiency
      and specificity of ADAR1 is examined in cell-based assays. A variety of dsRNA
      substrates was tested. It was found that a 15-bp dsRNA stem with a single base
      mismatch was sufficient for editing. The particular adenosine modified could be
      varied by changing the position of the mismatch. Editing efficiency could be
      increased by placing multiple pyrimidines 5' to the edited adenosine. With longer
      substrates, editing efficiency also increased and was partly due to the use of
      DRBMs. Additional editing sites were also observed that clustered on the
      complementary strand 11-15 bp from the first. An unexpected finding was that the
      DRBMs are not necessary for the editing of the shorter 15-bp substrates. However,
      mutation of the Z-DNA-binding domains of ADAR1 decreased the efficiency with
      which such a substrate was edited.

PMID- 11593028
TI  - CD26-mediated signaling for T cell activation occurs in lipid rafts through its
      association with CD45RO.
AB  - CD26 is a T cell activation antigen that contains dipeptidyl peptidase IV
      activity and is known to bind adenosine deaminase. The mechanism by which CD26
      costimulation potentiates T cell receptor-mediated T cell activation, leading to
      subsequent exertion of T cell effector function, is still not clearly defined. In
      this article, we demonstrate that CD26 localizes into lipid rafts, and targeting
      of CD26 to rafts is necessary for signaling events through CD26. Importantly,
      aggregation of CD26 by anti-CD26 mAb crosslinking also causes coaggregation of
      CD45 into rafts. Moreover, we show that CD26 directly binds to the cytoplasmic
      domain of CD45. Our results therefore indicate a mechanism whereby CD26
      engagement promotes aggregation of lipid rafts and facilitates colocalization of
      CD45 to T cell receptor signaling molecules p56(Lck), ZAP-70, and TCRzeta,
      thereby enhancing protein tyrosine phosphorylation of various signaling molecules
      and subsequent interleukin-2 production.

PMID- 11593029
TI  - HIV-1 Nef impairs MHC class II antigen presentation and surface expression.
AB  - HIV-1-infected cells can avoid cytotoxic T lymphocyte killing by Nef-mediated
      down-regulation of surface MHC I. Here, we show that HIV-1 Nef inhibits MHC II
      restricted peptide presentation to specific T cells and thus may affect the
      induction of antiviral immune responses. Nef mediates this effect by reducing the
      surface level of mature (i.e., peptide-loaded) MHC II while increasing levels of
      immature MHC II, which are functionally incompetent because of their association
      with the invariant chain. Nef was the only HIV-1 gene product to possess this
      capacity, which was also observed in the context of the whole HIV-1 genome. Other
      proteins of the endocytic pathway were not affected by Nef expression, suggesting
      that Nef effects on MHC II did not result from a general alteration of the
      endocytic pathway. Response patterns to previously characterized mutations of Nef
      differed for Nef-induced modulation of mature and immature MHC II. Furthermore,
      the doses of Nef required to observe each of the two effects were clearly
      different, suggesting that Nef could affect MHC II peptide presentation through
      distinct mechanisms. Cooperation between those mechanisms may enable Nef to
      efficiently inhibit MHC II function.

PMID- 11593030
TI  - Secreted MD-2 is a large polymeric protein that efficiently confers
      lipopolysaccharide sensitivity to Toll-like receptor 4.
AB  - Toll-like receptor 4 (TLR4), the principal signaling receptor for
      lipopolysaccharide (LPS) in mammals, requires the binding of MD-2 to its
      extracellular domain for maximal responsiveness. MD-2 contains a leader sequence
      but lacks a transmembrane domain, and we asked whether it is secreted into the
      medium as an active protein. As a source of secreted MD-2 (sMD-2), we used
      culture supernatants from cells stably transduced with epitope-tagged human MD-2.
      We show that sMD-2 exists as a heterogeneous collection of large disulfide-linked
      oligomers formed from stable dimeric subunits and that concentrations of sMD-2 as
      low as 50 pM enhance the responsiveness of TLR4 reporter cells to LPS. An MD-2
      like activity is also released by monocyte-derived dendritic cells from normal
      donors. When coexpressed, TLR4 indiscriminately associates in the endoplasmic
      reticulum/cis Golgi with different-sized oligomers of MD-2, and excess MD-2 is
      secreted into the medium. We conclude that normal and transfected cells secrete a
      soluble form of MD-2 that binds with high affinity to TLR4 and that could play a
      role in regulating responses to LPS and other pathogen-derived substances in
      vivo.

PMID- 11593031
TI  - TNF-alpha -dependent maturation of local dendritic cells is critical for
      activating the adaptive immune response to virus infection.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is well recognized for its role in
      mediating innate immune responses. However, the mechanisms of TNF-alpha that
      influence the adaptive immune response to virus infections are not well
      understood. In this study, we have investigated the role of TNF-alpha in
      activating the cellular and humoral responses to systemic viral challenge with
      recombinant replication-defective adenovirus (rAd). Evaluation of T cell function
      in TNF-alpha-deficient (TNFKO) mice revealed impaired virus-specific
      proliferation of T cells derived from the draining lymph nodes of the liver.
      Analysis of dendritic cells (DC) isolated from local draining lymph nodes after
      systemic challenge showed that DC from TNFKO mice were relatively immature
      compared with those from strain-matched wild-type mice. In vitro, TNF-alpha was
      required to mature DC efficiently during virus-mediated stimulation. Adoptive
      transfer of primed, mature DC into TNFKO mice restored T cell responses and
      reconstituted anti-adenovirus antibody responses. Thus, TNF-alpha plays a
      significant role in the maturation of DC after adenovirus challenge both in vitro
      and in vivo, highlighting the importance of this innate cytokine in activating
      adaptive immunity to viral challenge.

PMID- 11593032
TI  - Specific treatment of autoimmunity with recombinant invariant chains in which
      CLIP is replaced by self-epitopes.
AB  - The invariant chain (Ii) binds to newly synthesized MHC class II molecules with
      the CLIP region of Ii occupying the peptide-binding groove. Here we demonstrate
      that recombinant Ii proteins with the CLIP region replaced by antigenic self
      epitopes are highly efficient in activating and silencing specific T cells in
      vitro and in vivo. The Ii proteins require endogenous processing by antigen
      presenting cells for efficient T cell activation. An Ii protein encompassing the
      epitope myelin basic protein amino acids 84-96 (Ii-MBP84-96) induced the model
      autoimmune disease experimental allergic encephalomyelitis (EAE) with a higher
      severity and earlier onset than the peptide. When applied in a tolerogenic
      manner, Ii-MBP84-96 abolished antigen-specific T cell proliferation and
      suppressed peptide-induced EAE more effectively than peptide alone. Importantly,
      i.v. administration of Ii proteins after EAE induction completely abrogated the
      disease, whereas peptides only marginally suppressed disease symptoms. Ii fusion
      proteins are thus more efficient than peptide in modulating CD4(+) T cell
      mediated autoimmunity, documenting their superior qualities for therapeutic
      antigen delivery in vivo.

PMID- 11593033
TI  - Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of
      the Pkd1 gene.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst
      formation in the kidney, liver, and pancreas and is associated often with
      cardiovascular abnormalities such as hypertension, mitral valve prolapse, and
      intracranial aneurysms. It is caused by mutations in PKD1 or PKD2, encoding
      polycystin-1 and -2, which together form a cell surface nonselective cation ion
      channel. Pkd2-/- mice have cysts in the kidney and pancreas and defects in
      cardiac septation, whereas Pkd1(del34) -/- and Pkd1(L) -/- mice have cysts but no
      cardiac abnormalities, although vascular fragility was reported in the latter.
      Here we describe mice carrying a targeted mutation in Pkd1 (Pkd1(del17
      21betageo)), which defines its expression pattern by using a lacZ reporter gene
      and may identify novel functions for polycystin-1. Although Pkd1(del17-21betageo)
      +/- adult mice develop renal and hepatic cysts, Pkd1(del17-21betageo) -/- embryos
      die at embryonic days 13.5-14.5 from a primary cardiovascular defect that
      includes double outflow right ventricle, disorganized myocardium, and abnormal
      atrio-ventricular septation. Skeletal development is also severely compromised.
      These abnormalities correlate with the major sites of Pkd1 expression. During
      nephrogenesis, Pkd1 is expressed in maturing tubular epithelial cells from
      embryonic day 15.5. This expression coincides with the onset of cyst formation in
      Pkd1(del34) -/-, Pkd1(L) -/-, and Pkd2-/- mice, supporting the hypothesis that
      polycystin-1 and polycystin-2 interact in vivo and that their failure to do so
      leads to abnormalities in tubule morphology and function.

PMID- 11593034
TI  - Targeting tissue factor on tumor vascular endothelial cells and tumor cells for
      immunotherapy in mouse models of prostatic cancer.
AB  - The efficacy and safety of an immunoconjugate (icon) molecule, composed of a
      mutated mouse factor VII (mfVII) targeting domain and the Fc effector domain of
      an IgG1 Ig (mfVII/Fc icon), was tested with a severe combined immunodeficient
      (SCID) mouse model of human prostatic cancer and an immunocompetent mouse model
      of mouse prostatic cancer. The SCID mice were first injected s.c. with a human
      prostatic tumor line, forming a skin tumor that produces a high blood titer of
      prostate-specific antigen and metastasizes to bone. The icon was encoded in a
      replication-incompetent adenoviral vector that was injected directly into the
      skin tumor. The tumor cells infected by the vector synthesize and secrete the
      icon into the blood, and the blood-borne icon binds with high affinity and
      specificity to mouse tissue factor expressed on endothelial cells lining the
      lumen of the tumor vasculature and to human tissue factor expressed on the tumor
      cells. The Fc domain of the icon activates a cytolytic immune attack against
      cells that bind the icon. The immunotherapy tests in SCID mice demonstrated that
      intratumoral injections of the adenoviral vector encoding the mfVII/human Fc icon
      resulted in long-term regression of the injected human prostatic tumor and also
      of a distant uninjected tumor, without associated toxicity to the mice.
      Comparable results were obtained with a SCID mouse model of human melanoma. At
      the end of the experiments the mice appeared to be free of viable tumor cells.
      This protocol also could be efficacious for treating cancer patients who have
      vascularized tumors.

PMID- 11593035
TI  - PS1 N- and C-terminal fragments form a complex that functions in APP processing
      and Notch signaling.
AB  - Presenilin proteins play critical roles in the proteolytic processing of both
      Notch and amyloid precursor protein (APP). Presenilin itself undergoes
      endoproteolytic processing to generate an N-terminal and C-terminal fragment. As
      demonstrated previously, overexpression of presenilin 1 (PS1) holoprotein does
      not change the levels of the N-terminal and C-terminal fragments (NTF and CTF).
      When we coexpress the PS1 NTF and CTF, marked increases in the cellular levels of
      these fragments are seen. By coexpressing the PS1 NTF and CTF, we demonstrate
      conclusively that a noncovalent complex of the NTF and CTF is the active species
      of presenilin. However, although the PS1 NTF/CTF complex is necessary for gamma
      secretase activity, it is not sufficient. Independent overexpression of the PS1
      NTF and CTF was also used to show that the Asp-257 and Asp-385 mutations in PS1
      decrease Abeta production by a direct effect on gamma-secretase activity and not
      by the inhibition of PS1 endoproteolysis.

PMID- 11593036
TI  - Suppressor of cytokine signaling 3 (SOCS-3) protects beta -cells against
      interleukin-1beta - and interferon-gamma -mediated toxicity.
AB  - Suppressor of cytokine signaling 3 (SOCS-3) is a negative feedback regulator of
      IFN-gamma signaling, shown up-regulated in mouse bone marrow cells by the
      proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor
      alpha (TNF-alpha), and IFN-gamma. IL-1beta and IFN-gamma alone, or potentiated by
      TNF-alpha, are cytotoxic to the insulin producing pancreatic beta-cells and beta
      cell lines in vitro and suggested to contribute to the specific beta-cell
      destruction in Type-1 diabetes mellitus (T1DM). Using a doxycycline-inducible
      SOCS-3 expression system in the rat beta-cell line INS-1, we demonstrate that the
      toxic effect of both IL-1beta or IFN-gamma at concentrations that reduced the
      viability by 50% over 3 days, was fully preventable when SOCS-3 expression was
      turned on in the cells. At cytokine concentrations or combinations more toxic to
      the cells, SOCS-3 overexpression yielded a partial protection. Whereas SOCS-3
      mediated inhibition of IFN-gamma signaling is described in other cell systems,
      SOCS-3 mediated inhibition of IL-1beta signaling has not previously been
      described. In addition we show that SOCS-3 prevention of IL-1beta-induced
      toxicity is accompanied by inhibited transcription of the inducible nitric oxide
      synthase (iNOS) by 80%, resulting in 60% decreased formation of the toxic nitric
      oxide (NO). Analysis of isolated native rat islets exposed to IL-1beta revealed a
      naturally occurring but delayed up-regulated SOCS-3 transcription. Influencing
      SOCS-3 expression thus represents an approach for affecting cytokine-induced
      signal transduction at a proximal step in the signal cascade, potentially useful
      in future therapies aimed at reducing the destructive potential of beta-cell
      cytotoxic cytokines in T1DM, as well as other cytokine-dependent diseases.

PMID- 11593037
TI  - Comparison of mechanisms of action of luteinizing hormone-releasing hormone
      (LHRH) antagonist cetrorelix and LHRH agonist triptorelin on the gene expression
      of pituitary LHRH receptors in rats.
AB  - The mechanisms through which luteinizing hormone (LH)-releasing hormone (LHRH)
      antagonists suppress pituitary gonadotroph functions and LHRH-receptor (LHRH-R)
      expression are incompletely understood. Consequently, we investigated the direct
      effect of LHRH antagonist cetrorelix in vitro on the expression of the pituitary
      LHRH-R gene and its ability to counteract the exogenous LHRH and the agonist
      triptorelin in the regulation of this gene. We also compared the effects of
      chronic administration of cetrorelix and triptorelin on the LHRH-R mRNA level and
      gonadotropin secretion in ovariectomized (OVX) and normal female rats. The
      exposure of pituitary cells in vitro to 3-min pulses of 1 nM LHRH or 0.1 nM
      triptorelin for 5 h increased the LHRH-R mRNA level by 77-88%. Continuous
      perfusion of the cells with 50 nM cetrorelix did not cause any significant
      changes, but prevented the stimulatory effect of LHRH pulses on the receptor mRNA
      expression. In OVX rats, 10 days after administration of a depot formulation of
      cetrorelix, releasing 100 microg of peptide daily, the elevated LHRH-R mRNA level
      was decreased by 73%, whereas daily injection of 100 microg of triptorelin caused
      a 41% suppression. In normal female rats, cetrorelix treatment suppressed the
      LHRH-R mRNA level by 33%, but triptorelin increased it by 150%. The highly
      elevated serum LH levels in OVX rats and the normal LH concentration of cycling
      rats were rapidly and completely suppressed by cetrorelix. Triptorelin decreased
      the serum LH in OVX rats to the precastration level, but had no effect on basal
      LH in normal rats. Our results confirm that LHRH antagonists, such as cetrorelix,
      inhibit the gene expression of pituitary LHRH-R indirectly, by counteracting the
      stimulatory effect of LHRH. A rapid suppression of serum LH by LHRH antagonists
      would be advantageous in the treatment of sex hormone-dependent tumors and other
      conditions.

PMID- 11593038
TI  - Regulation of human heme oxygenase in endothelial cells by using sense and
      antisense retroviral constructs.
AB  - Our objective was to determine whether overexpression and underexpression of
      human heme oxygenase (HHO)-1 could be controlled on a long-term basis by
      introduction of the HO-1 gene in sense (S) and antisense (AS) orientation with an
      appropriate vector into endothelial cells. Retroviral vector (LXSN) containing
      viral long terminal repeat promoter-driven human HO-1 S (LSN-HHO-1) and LXSN
      vectors containing HHO-1 promoter (HOP)-controlled HHO-1 S and AS (LSN-HOP-HHO-1
      and LSN-HOP-HHO-1-AS) sequences were constructed and used to transfect rat lung
      microvessel endothelial cells (RLMV cells) and human dermal microvessel
      endothelial cells (HMEC-1 cells). RLMV cells transduced with HHO-1 S expressed
      human HO-1 mRNA and HO-1 protein associated with elevation in total HO activity
      compared with nontransduced cells. Vector-mediated expression of HHO-1 S or AS
      under control of HOP resulted in effective production of HO-1 or blocked
      induction of endogenous human HO-1 in HMEC-1 cells, respectively. Overexpression
      of HO-1 AS was associated with a long-term decrease (45%) of endogenous HO-1
      protein and an increase (167%) in unmetabolized exogenous heme in HMEC-1 cells.
      Carbon monoxide (CO) production in HO-1 S- or AS-transduced HMEC-1 cells after
      heme treatment was increased (159%) or decreased (50%), respectively, compared
      with nontransduced cells. HO-2 protein levels did not change. These findings
      demonstrate that HHO-1 S and AS retroviral constructs are functional in enhancing
      and reducing HO activity, respectively, and thus can be used to regulate cellular
      heme levels, the activity of heme-dependent enzymes, and the rate of heme
      catabolism to CO and bilirubin.

PMID- 11593039
TI  - Dynamic copy choice: steady state between murine leukemia virus polymerase and
      polymerase-dependent RNase H activity determines frequency of in vivo template
      switching.
AB  - We recently proposed a dynamic copy-choice model for retroviral recombination in
      which a steady state between the rates of polymerization and RNA degradation
      determines the frequency of reverse transcriptase (RT) template switching. The
      relative contributions of polymerase-dependent and polymerase-independent RNase H
      activities during reverse transcription and template switching in vivo have not
      been determined. We developed an in vivo trans-complementation assay in which
      direct repeat deletion through template switching reconstitutes a functional
      green fluorescent protein gene in a retroviral vector. Complementation in trans
      between murine leukemia virus Gag-Pol proteins lacking polymerase and RNase H
      activities restored viral replication. Because only polymerase-independent RNase
      H activity is present in this cell line, the relative roles of polymerase
      dependent and -independent RNase H activities in template switching could be
      determined. We also analyzed double mutants possessing polymerase and RNase H
      mutations that increased and decreased template switching, respectively. The
      double mutants exhibited low template switching frequency, indicating that the
      RNase H mutations were dominant. Trans-complementation of the double mutants with
      polymerase-independent RNase H did not restore the high template switching
      frequency, indicating that polymerase-dependent RNase H activity was essential
      for the increased frequency of template switching. Additionally, trans
      complementation of RNase H mutants in the presence and absence of hydroxyurea,
      which slows the rate of reverse transcription, showed that hydroxyurea increased
      template switching only when polymerase-dependent RNase H activity was present.
      This is, to our knowledge, the first demonstration of polymerase-dependent RNase
      H activity in vivo. These results provide strong evidence for a dynamic
      association between the rates of DNA polymerization and polymerase-dependent
      RNase H activity, which determines the frequency of in vivo template switching.

PMID- 11593040
TI  - Poly(ADP-ribose) glycohydrolase mediates oxidative and excitotoxic neuronal
      death.
AB  - Excessive activation of poly(ADP-ribose) polymerase 1 (PARP1) leads to NAD(+)
      depletion and cell death during ischemia and other conditions that generate
      extensive DNA damage. When activated by DNA strand breaks, PARP1 uses NAD(+) as
      substrate to form ADP-ribose polymers on specific acceptor proteins. These
      polymers are in turn rapidly degraded by poly(ADP-ribose) glycohydrolase (PARG),
      a ubiquitously expressed exo- and endoglycohydrolase. In this study, we examined
      the role of PARG in the PARP1-mediated cell death pathway. Mouse neuron and
      astrocyte cultures were exposed to hydrogen peroxide, N-methyl-d-aspartate
      (NMDA), or the DNA alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).
      Cell death in each condition was markedly reduced by the PARP1 inhibitor
      benzamide and equally reduced by the PARG inhibitors gallotannin and nobotanin B.
      The PARP1 inhibitor benzamide and the PARG inhibitor gallotannin both prevented
      the NAD(+) depletion that otherwise results from PARP1 activation by MNNG or
      H(2)O(2). However, these agents had opposite effects on protein poly(ADP
      ribosyl)ation. Immunostaining for poly(ADP-ribose) on Western blots and neuron
      cultures showed benzamide to decrease and gallotannin to increase poly(ADP
      ribose) accumulation during MNNG exposure. These results suggest that PARG
      inhibitors do not inhibit PARP1 directly, but instead prevent PARP1-mediated cell
      death by slowing the turnover of poly(ADP-ribose) and thus slowing NAD(+)
      consumption. PARG appears to be a necessary component of the PARP-mediated cell
      death pathway, and PARG inhibitors may have promise as neuroprotective agents.

PMID- 11593041
TI  - SNARE-complex disassembly by NSF follows synaptic-vesicle fusion.
AB  - Soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE)
      mediated fusion of synaptic vesicles with the presynaptic-plasma membrane is
      essential for communication between neurons. Disassembly of the SNARE complex
      requires the ATPase N-ethylmaleimide-sensitive fusion protein (NSF). To determine
      where in the synaptic-vesicle cycle NSF functions, we have undertaken a genetic
      analysis of comatose (dNSF-1) in Drosophila. Characterization of 16 comatose
      mutations demonstrates that NSF mediates disassembly of SNARE complexes after
      synaptic-vesicle fusion. Hypomorphic mutations in NSF cause temperature-sensitive
      paralysis, whereas null mutations result in lethality. Genetic-interaction
      studies with para demonstrate that blocking evoked fusion delays the accumulation
      of assembled SNARE complexes and behavioral paralysis that normally occurs in
      comatose mutants, indicating NSF activity is not required in the absence of
      vesicle fusion. In addition, the entire vesicle pool can be depleted in shibire
      comatose double mutants, demonstrating that NSF activity is not required for the
      fusion step itself. Multiple rounds of vesicle fusion in the absence of NSF
      activity poisons neurotransmission by trapping SNAREs into cis-complexes. These
      data indicate that NSF normally dissociates and recycles SNARE proteins during
      the interval between exocytosis and endocytosis. In the absence of NSF activity,
      there are sufficient fusion-competent SNAREs to exocytose both the readily
      released and the reserve pool of synaptic vesicles.

PMID- 11593042
TI  - Shifts in cortical representations predict human discrimination improvement.
AB  - We report experiments combining assessment of spatial tactile discrimination
      behavior and measurements of somatosensory-evoked potentials in human subjects
      before and after short-term plastic changes to demonstrate a causal link between
      the degree of altered performance and reorganization. Plastic changes were
      induced by a Hebbian coactivation protocol of simultaneous pairing of tactile
      stimuli. As a result of coactivation, spatial discrimination thresholds were
      lowered; however, the amount of discrimination improvement was variable across
      subjects. Analysis of somatosensory-evoked potentials revealed a significant, but
      also variable shift in the localization of the N20-dipole of the index finger
      that was coactivated. The Euclidean distance between the dipole pre- and post
      coactivation was significantly larger on the coactivated side (mean 9.13 +/- 3.4
      mm) than on the control side (mean 4.90 +/- 2.7 mm, P = 0.008). Changes of polar
      angles indicated a lateral and inferior shift on the postcentral gyrus of the
      left hemisphere representing the coactivated index finger. To explore how far the
      variability of improvement was reflected in the degree of reorganization, we
      correlated the perceptual changes with the N20-dipole shifts. We found that the
      changes in discrimination abilities could be predicted from the changes in dipole
      localization. Little gain in spatial discrimination was associated with small
      changes in dipole shifts. In contrast, subjects who showed a large cortical
      reorganization also had lowest thresholds. All changes were highly selective as
      no transfer to the index finger of the opposite, non-coactivated hand was found.
      Our results indicate that human spatial discrimination performance is subject to
      improvement on a short time scale by a Hebbian stimulation protocol without
      invoking training, attention, or reinforcement. Plastic processes related to the
      improvement were localized in primary somatosensory cortex and were scaled with
      the degree of the individual perceptual improvement.

PMID- 11593043
TI  - An analysis of neural receptive field plasticity by point process adaptive
      filtering.
AB  - Neural receptive fields are plastic: with experience, neurons in many brain
      regions change their spiking responses to relevant stimuli. Analysis of receptive
      field plasticity from experimental measurements is crucial for understanding how
      neural systems adapt their representations of relevant biological information.
      Current analysis methods using histogram estimates of spike rate functions in
      nonoverlapping temporal windows do not track the evolution of receptive field
      plasticity on a fine time scale. Adaptive signal processing is an established
      engineering paradigm for estimating time-varying system parameters from
      experimental measurements. We present an adaptive filter algorithm for tracking
      neural receptive field plasticity based on point process models of spike train
      activity. We derive an instantaneous steepest descent algorithm by using as the
      criterion function the instantaneous log likelihood of a point process spike
      train model. We apply the point process adaptive filter algorithm in a study of
      spatial (place) receptive field properties of simulated and actual spike train
      data from rat CA1 hippocampal neurons. A stability analysis of the algorithm is
      sketched in the. The adaptive algorithm can update the place field parameter
      estimates on a millisecond time scale. It reliably tracked the migration, changes
      in scale, and changes in maximum firing rate characteristic of hippocampal place
      fields in a rat running on a linear track. Point process adaptive filtering
      offers an analytic method for studying the dynamics of neural receptive fields.

PMID- 11593044
TI  - Increased anxiety and synaptic plasticity in estrogen receptor beta -deficient
      mice.
AB  - Estrogens are powerful modulators of neuronal physiology and in humans may affect
      a broad range of functions, including reproductive, emotional, and cognitive
      behaviors. We studied the contribution of estrogen receptors (ERs) in modulation
      of emotional processes and analyzed the effects of deleting ERalpha or ERbeta in
      mice. Behavior consistent with increased anxiety was observed principally in
      ERbeta mutant females and was associated with a reduced threshold for the
      induction of synaptic plasticity in the basolateral amygdala. Local increase of 5
      hydroxytryptamine 1a receptor expression in medial amygdala may contribute to
      these changes. Our data show that, particularly in females, there is an important
      role for ERbeta-mediated estrogen signaling in the processing of emotional
      behavior.

PMID- 11593045
TI  - The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive
      cardiomyopathy.
AB  - Stress-induced mitogen-activated protein kinase (MAP) p38 is activated in various
      forms of heart failure, yet its effects on the intact heart remain to be
      established. Targeted activation of p38 MAP kinase in ventricular myocytes was
      achieved in vivo by using a gene-switch transgenic strategy with activated
      mutants of upstream kinases MKK3bE and MKK6bE. Transgene expression resulted in
      significant induction of p38 kinase activity and premature death at 7-9 weeks.
      Both groups of transgenic hearts exhibited marked interstitial fibrosis and
      expression of fetal marker genes characteristic of cardiac failure, but no
      significant hypertrophy at the organ level. Echocardiographic and pressure-volume
      analyses revealed a similar extent of systolic contractile depression and
      restrictive diastolic abnormalities related to markedly increased passive chamber
      stiffness. However, MKK3bE-expressing hearts had increased end-systolic chamber
      volumes and a thinned ventricular wall, associated with heterogeneous myocyte
      atrophy, whereas MKK6bE hearts had reduced end-diastolic ventricular cavity size,
      a modest increase in myocyte size, and no significant myocyte atrophy. These data
      provide in vivo evidence for a negative inotropic and restrictive diastolic
      effect from p38 MAP kinase activation in ventricular myocytes and reveal specific
      roles of p38 pathway in the development of ventricular end-systolic remodeling.

PMID- 11593046
TI  - Translation of chloroplast psbA mRNA is regulated by signals initiated by both
      photosystems II and I.
AB  - Light controls the translation of several mRNAs in fully developed chloroplasts
      via at least two regulatory pathways. In the first, the light signal is
      transduced as a thiol-mediated signal that modulates translation in parallel to
      light intensity. The second light-controlled pathway, termed priming, is a
      prerequisite to the thiol-mediated regulatory pathway. Light regulation is rapid
      and requires intrachloroplast photoreceptor(s). To delineate the signaling
      pathways controlling each of these regulatory events, we assayed the effect of
      photosynthetic inhibitors and electron donors on the translation of chloroplastic
      psbA mRNA. We show that the thiol-mediated signal is generated by photosystem I
      and transduced by vicinal dithiol-containing proteins. We also found that the
      priming signal probably initiates on reduction of plastoquinone. These findings
      suggest that translation of chloroplast psbA mRNA is controlled by both linear
      photosynthetic electron transport, exerted by the reduction of the ferredoxin
      thioredoxin system, and the relative activities of photosystems I and II,
      signaled by the redox state of the plastoquinone pool. These data underscore the
      function of the light-capturing reactions of photosynthesis as chloroplast
      photoreceptors.

PMID- 11593047
TI  - Mammalian Bax-induced plant cell death can be down-regulated by overexpression of
      Arabidopsis Bax Inhibitor-1 (AtBI-1).
AB  - We recently isolated the AtBI-1 (Arabidopsis Bax Inhibitor-1) gene, the
      expression of which suppressed Bax-induced cell death in yeast. To determine
      whether the same is true in the plant system, transgenic Arabidopsis plants
      overexpressing Bax protein under a dexamethasone (DEX)-inducible promoter were
      generated. On DEX treatment, such transgenic plants exhibited marked cell death
      at the whole-plant level, cell shrinkage, membranous destruction, and other
      apoptotic phenotypes. Transgenic Bax plants were retransformed with a vector
      containing the AtBI-1 gene (tagged with green fluorescent protein) under the
      control of the cauliflower mosaic virus 35S promoter. Plants expressing both Bax
      and AtBI-1 were able to maintain growth on DEX-treatment by sustaining
      intracellular integrity. Thus, we present here direct genetic evidence that the
      plant antiapoptotic protein AtBI-1 is biologically active in suppressing the
      mammalian Bax action in planta.

PMID- 11593048
TI  - Different patterns of human discrimination learning for two interaural cues to
      sound-source location.
AB  - Two of the primary cues used to localize the sources of sounds are interaural
      level differences (ILDs) and interaural time differences (ITDs). We conducted two
      experiments to explore how practice affects the human discrimination of values of
      ILDs and ongoing ITDs presented over headphones. We measured discrimination
      thresholds of 13 to 32 naive listeners in a variety of conditions during a
      pretest and again, 2 weeks later, during a posttest. Between those two tests, we
      trained a subset of listeners 1 h per day for 9 days on a single ILD or ITD
      condition. Listeners improved on both ILD and ITD discrimination. Improvement was
      initially rapid for both cue types and appeared to generalize broadly across
      conditions, indicating conceptual or procedural learning. A subsequent slower
      improvement stage, which occurred solely for the ILD cue, only affected
      conditions with the trained stimulus frequency, suggesting that stimulus
      processing had fundamentally changed. These different learning patterns indicate
      that practice affects the attention to, or low-level encoding of, ILDs and ITDs
      at sites at which the two cue types are processed separately. Thus, these data
      reveal differences in the effect of practice on ILD and ITD discrimination, and
      provide insight into the encoding of these two cues to sound-source location in
      humans.

PMID- 11593049
TI  - Cell signalling - the proteomics of it all.
AB  - A challenge for biomedical scientists today is to arrive at an understanding of
      cellular behavior on a global scale. The advent of DNA microarrays has greatly
      facilitated discovery of gene expression profiles associated with different
      cellular states. The problem of understanding cellular signaling at the level of
      the interacting proteins is in some ways more challenging. Ashman et al. discuss
      the current methods available for studying protein interactions on a global
      scale, as well as directions for the future. Technical hurdles exist at many
      stages, from the isolation of protein complexes, to the determination of their
      composition, to the software and databases needed to analyze the results of large
      scale, high-throughput datasets. Ashman et al. suggest that, with advances in
      technology and cooperation among academia and industry, a global protein
      interaction map that underlies cellular behavior will emerge as an essential
      resource for basic and applied research.

PMID- 11593050
TI  - Identification of cell signaling molecules by expression cloning.
AB  - Using expression cloning one can isolate proteins with specific biological
      functions. This methodology can be adapted for the identification of novel
      players in the regulation of cell signaling. Here, we describe an expression
      cloning strategy to identify suppressors of Ras signaling. This screen is based
      on the observation that the activation of the small guanosine triphosphate (GTP)
      binding protein H-Ras initiates a mitogen-activated protein kinase (MAPK)
      dependent signaling pathway that inactivates integrin ligand binding. Our
      strategy depends on flow cytometry and a monoclonal antibody that recognizes
      integrin activation states. Flow cytometry enhances the screen's sensitivity
      thereby allowing us to examine function quantitatively at the level of a single
      cell millions of times in one screen. The following protocol provides a detailed
      method for the isolation of proteins that regulate cell signaling.

PMID- 11593052
TI  - Phase II study of high-dose megestrol acetate in platinum-refractory epithelial
      ovarian cancer.
AB  - Our objective was to determine the efficacy of megestrol acetate in the treatment
      of platinum-refractory epithelial ovarian cancer (EOC), and to evaluate the
      toxicities and quality of life (QOL) associated with this therapy. Patients with
      platinum-resistant epithelial ovarian cancer were treated with megestrol acetate
      (800 mg/day) orally for 28 days and then 400 mg/day for a minimum of 28 days
      before being assessed ready for evaluation of response to therapy. Patients who
      demonstrated a complete response (CR), partial response (PR) or stable disease
      were continued in the study until there was objective evidence of disease
      progression. All patients who went off study were followed up at regular
      intervals, every 2 months, to assess overall survival. Thirty-six patients were
      enrolled. Response was observed in seven of 36 patients (three CR and four PR).
      The response rate was 19.4% (95% CI 9-36). Four of the responders had the
      endometrioid cell type, while two were clear cell carcinoma and one was
      serouscystadenocarcinoma. All three CR patients had the histology of endometrioid
      carcinoma with the tumors located in the pelvis. Median survival of the study
      population was 5.8 months. Median survival in the responders was 12 months, while
      median survival in the non-responders was 5.5 months. Median progression-free
      survival in the responders was 8.3 months, while median progression-free survival
      in the non-responders was only 2 months. The majority of patients gained weight
      and had a fair quality of life score during treatment. The only toxicity observed
      was alopecia (grade 1) in four patients. We conclude that megestrol acetate has
      modest but definite activity in patients with platinum-refractory EOC,
      particularly in a small subset of the endometrioid subtype with limited disease
      in the pelvis. Only minimal toxicity was observed and the patients had a fair QOL
      score during the treatment.

PMID- 11593051
TI  - Phase I trial of weekly gemcitabine at 3-h infusion in refractory, heavily
      pretreated advanced solid tumors.
AB  - Gemcitabine (2',2'-difluorodeoxycytidine) is a nucleoside analog with antitumor
      activity against a variety of malignancies. The critical enzyme cytidine kinase
      is saturated at plasma concentrations achieved after a 30-min infusion at
      conventional doses. Prolonged infusion time may yield higher intracellular dFdCTP
      concentrations. A phase I study was designed to determine the maximum tolerated
      dose (MTD) of gemcitabine, given by infusion for 3 h, in heavily pretreated
      patients. Twenty-seven patients (13 head and neck cancer, seven sarcoma, three
      esophageal cancer, three non-small-cell lung cancer and one ovarian cancer) were
      enrolled. Twenty patients were defined as refractory at first- or second-line
      chemotherapy. Four different entry dose levels (300, 400, 450 and 500 mg/m(2))
      were evaluated for gemcitabine administered on days 1, 8 and 15 of a 28-day
      cycle. The MTD was defined as 450 mg/m(2), with granulocytopenia,
      thrombocytopenia and asthenia being dose limiting. The maximum grade III/IV
      patient toxicities for hemoglobin, leukocytes, neutrophils and platelets for all
      doses were 7, 19, 19 and 11%, respectively. Non-hematological toxicities included
      asthenia, nausea/vomiting and diarrhea. Thus, gemcitabine administered at a fixed
      3-h infusion was well tolerated up to 450 mg/m(2) in heavily pretreated patients.
      Myelosupression and asthenia were dose-limiting toxicities.

PMID- 11593053
TI  - Efficacy and toxicity of bendamustine in patients with relapsed low-grade non
      Hodgkin's lymphomas.
AB  - Low-grade non-Hodgkin's lymphomas (NHL) are very sensitive to a broad range of
      chemotherapeutic and biological agents. Relapses, however, occur even after
      aggressive cytostatic combinations in first-line therapy. Therefore, effective
      and well-tolerated salvage therapies are very important. In this single
      institution trial, the efficacy and toxicity of bendamustine in the treatment of
      relapsed low-grade NHL was investigated. Fifty-eight patients with low-grade NHL
      pretreated with different cytostatic regimens were included. All patients
      received bendamustine at 120 mg/m(2) as a 1-h infusion on 2 consecutive days. The
      treatment was repeated every 3 weeks until complete remission (CR), partial
      remission (PR) or stable disease (SD) was confirmed on two consecutive cycles.
      Efficacy and toxicity were evaluated in 52 patients: CR was induced in 11%, PR in
      62% and SD in another 10% of the patients. No response to treatment was seen in
      17%. The median duration of remission was 16 months and the median survival time
      was 36 months. Side effects were generally mild, and restricted to
      myelosuppression, gastrointestinal toxicity and allergic reactions. Bendamustine
      proved to be very effective and was well tolerated in pretreated patients with
      relapsed or primary resistant low-grade NHL.

PMID- 11593054
TI  - Pamidronate-induced remission of pain associated with hypertrophic pulmonary
      osteoarthropathy in chemoendocrine therapy-refractory inoperable metastatic
      breast carcinoma.
AB  - We describe an extremely rare case of a woman with pulmonary metastatic disease
      from breast cancer, who presented with features of hypertrophic pulmonary
      osteoarthropathy (HPOA). Pain associated with HPOA may be extremely disabling and
      resistant to treatment. Treatment with pamidronate, an inhibitor of osteoclastic
      bone resorption, given every 2 weeks by i.v. drip infusion, led to rapid
      disappearance of uncontrolled pain caused by HPOA.

PMID- 11593055
TI  - Bryostatin 1 induces differentiation and potentiates the antitumor effect of
      Auristatin PE in a human pancreatic tumor (PANC-1) xenograft model.
AB  - Pancreatic cancer has the worst prognosis of all cancers with a dismal 5-year
      survival rate. Hence, there is a tremendous need for development of new and
      effective therapy for this tumor. In an earlier study we reported a potent
      antitumor activity of Auristatin PE (AuriPE) against pancreatic tumor. In
      addition, we have also reported that bryostatin 1 (bryo1) induces differentiation
      of leukemia cells, but the effect of bryo1 has not been investigated in
      pancreatic tumors. This is the first report where we demonstrate that bryo1
      induces differentiation and potentiates the antitumor effect of AuriPE in a human
      pancreatic tumor (PANC-1) xenograft model. A xenograft model was established by
      injecting the PANC-1 cells s.c. in severe combined immune deficient (SCID) mice.
      After development of the s.c. tumors, tumors were dissected and small fragments
      were transplanted in vivo to new SCID mice, with a success rate of 100% and a
      doubling time of 4.8 days. The SCID mouse xenograft model was used to test the in
      vivo differentiation effect of bryo1 and its efficacy when given alone or in
      combination with AuriPE. Sections from paraffin-embedded tumors excised from
      untreated (control) SCID mice revealed typical poorly differentiated
      adenocarcinoma of the pancreas. Interestingly, sections of s.c. tumors taken from
      bryo1-treated mice revealed carcinomas that were much lower grade and less
      aggressive, and displayed prominent squamous and glandular differentiation. In
      this study, the tumor growth inhibition (T/C), activity score and cure rate for
      bryo1, AuriPE and bryo1+AuriPE were 80%, (+) and 0/4; 0.0%, (++++) and 3/5; and
      0.0%, (++++) and 3/4, respectively. Mice treated with either AuriPE or
      bryo1+AuriPE were free of tumors for more than 150 days and were considered
      cured. The use of bryo1 as a novel differentiating agent and its combination with
      AuriPE should be further explored for the treatment of adenocarcinoma of the
      pancreas.

PMID- 11593056
TI  - Combination of oxaliplatin and irinotecan on human colon cancer cell lines:
      activity in vitro and in vivo.
AB  - The in vitro and in vivo combination of oxaliplatin and irinotecan was
      investigated in a panel of four human colon cancer cell lines and their
      counterpart xenografts. In vitro and in vivo experiments demonstrated a
      synergistic or additive interaction in three cell lines (HCT-116, HCT-8 and HT
      29) and an antagonism in SW-620 cells. Since there were clearly opposite
      interactions depending on the cell line, we further investigated cellular
      determinants possibly involved in the interaction between the two drugs in HCT-8
      and SW-620 cells. Irinotecan slowed down the early platinum-DNA adducts repair (1
      h after oxaliplatin exposure) in the presence of irinotecan only in HCT-8 cells
      (p=0.03, n=3). Moreover, a decrease of the expression of two proteins of the
      nucleotide excision repair (NER) system, ERCC1 and XPA, was observed. None of
      these effects was seen in SW-620 cells. Irinotecan induced apoptosis with an
      increase of poly(ADP-ribose) polymerase (PARP) cleavage in SW-620 cells (60
      versus 7% basal level). Pretreatment of these cells with oxaliplatin abolished
      the increase in PARP cleavage induced by irinotecan (29%). In HCT-8 cells, a very
      little PARP cleavage was observed whatever the drug treatment. The persistence of
      platinum-DNA adducts in the presence of irinotecan could be due to a direct
      impact of irinotecan on NER gene expression or to an indirect effect on
      topoisomerase I activity. Complementary studies are required to determine if the
      cellular parameters identified in this study could be translated at the clinical
      level to predict clinical response after combined treatment with oxaliplatin and
      irinotecan in humans.

PMID- 11593057
TI  - Response of short-term cultures derived from human malignant glioma to
      aziridinylbenzoquinone, etoposide and doxorubicin: an in vitro phase II trial.
AB  - The relative resistance of malignant glioma to chemotherapy makes the
      identification of new cytotoxic drugs critically important. The use of short-term
      cultures derived from these tumors to screen drugs at doses that can be attained
      within human intracranial tumors provides a model system that should be capable
      of identifying effective drugs suitable for clinical evaluation. The sensitivity
      of a panel of short-term cultures derived from 22 malignant astrocytoma and four
      malignant oligodendroglioma was assessed to aziridinylbenzoquinone (AZQ),
      etoposide and doxorubicin (DOX) using a [(35)S] methione uptake assay. The ID(50)
      of each culture was compared to the levels of drug which could be achieved in the
      tumor using standard doses. There was marked heterogeneity between cultures in
      response to each drug. Whilst there was no evidence that cultures derived from
      grade III astrocytoma were more sensitive to any of the drugs than cultures
      derived from grade IV astrocytoma, cultures derived from oligodendroglioma tended
      to be more sensitive to the alkylating agent AZQ, but not to either of the other
      drugs. The sensitivity of these short-term cultures at concentrations that can be
      achieved in situ corresponded well with the clinical efficacy of AZQ and
      etoposide. Although DOX appeared to be toxic to human gliomas cells in vitro, its
      limited penetration into the intact brain would seem to preclude its use i.v.,
      but it is likely to be effective if local drug delivery techniques could be
      employed. The study suggests that short-term cultures derived from malignant
      glioma should be used to screen investigational agents for potential clinical
      efficacy.

PMID- 11593058
TI  - Inhibition of growth and metastases of MDA-MB-435 human estrogen-independent
      breast cancers by an antagonist of growth hormone-releasing hormone.
AB  - Antagonists of growth hormone-releasing hormone (GH-RH) inhibit the growth of
      various cancers by mechanism(s) that include the suppression of the insulin-like
      growth factors (IGF)-I and/or -II. In this study, nude mice bearing orthotopic
      implants of MDA-MB-435 human estrogen-independent breast carcinoma received 39
      days of therapy with GH-RH antagonist JV-1-36 (20 microg/day). The treatment
      significantly inhibited tumor growth by 71.1% (p<0.01) and nullified the
      metastatic potential of MDA-MB-435 cells. Four of eight control mice (50%)
      developed metastases in the lymph nodes and one (12.5%) in the lung, but none of
      the animals receiving JV-1-36 showed metastatic spread. GH-RH antagonist JV-1-36
      inhibited the growth of MDA-MB-435 cells in vitro, while IGF-I stimulated it.
      However, mRNA for IGF-I or -II was not detected in MDA-MB-435 cells, indicating
      that the suppression of autocrine IGFs may not be involved in the
      antiproliferative mechanism. Using ligand competition assays with (125)I-labeled
      GH-RH antagonist JV-1-42, specific high-affinity binding sites for GH-RH were
      found on tumor membranes. Reverse transcription-polymerase chain reaction
      revealed the expression of mRNA for GH-RH receptor splice variant-1 in MDA-MB-435
      tumors. Our results suggest that the antitumorigenic action of GH-RH antagonists
      on MDA-MB-435 breast cancer could be direct and mediated by tumoral GH-RH
      receptors.

PMID- 11593059
TI  - Establishment and characterization of adriamycin-resistant human colorectal
      adenocarcinoma HCT-15 cell lines with multidrug resistance.
AB  - The multidrug resistance (MDR) phenotype, either intrinsic and/or acquired, is
      discussed in relation to several MDR-associated markers such as P-glycoprotein (P
      gp) encoded by mdr1, multidrug-resistance-associated protein (MRP) encoded by MRP
      and lung-resistance-associated protein (LRP) encoded by LRP. Well-characterized
      in vitro models are required to elucidate the mechanisms of MDR. The aim of the
      present study is the establishment of a drug-resistant subline from human
      colorectal adenocarcinoma HCT-15 that intrinsically expresses moderate levels of
      P-gp, MRP and LRP. Three adriamycin-resistant sublines (HCT-15/ADM1, HCT-15/ADM2
      and HCT-15/ADM2-2) were established by stepwise exposure in growth medium that
      was supplemented with 25-200 ng/ml adriamycin-resulting in a 2.2- to 7.8-fold
      increase in IC(50) values by using the XTT assay. They were cross-resistant to
      MDR-related drugs, epirubicin, mitoxantrone, vincristine, etoposide and taxol,
      but not the MDR-unrelated drug, mytomycin C. The resistance to adriamycin was
      confirmed in vivo by a lack of sensitivity in athymic nude mice. Gene expression
      data for mdr1/P-gp, MRP/MRP and LRP/LRP on both mRNA and protein levels
      demonstrated that the molecules contributing to MDR in resistant sublines are
      mainly P-gp and partially MRP. The newly established adriamycin-resistant
      sublines of HCT-15 will provide clinically relevant tools to investigate how to
      overcome drug resistance and elucidate possible mechanisms of acquired MDR in
      human colon cancer.

PMID- 11593060
TI  - Tumor cytotoxicity of peritoneal macrophages induced by OK-432.
AB  - In the present study we investigated the enhancement of cytotoxicity of
      peritoneal macrophages induced by OK-432. Rats received an i.p. injection of OK
      432 at doses of 0.1, 0.5 or 1.0 KE/rat. Two days later, rats were sacrificed and
      peritoneal macrophages were isolated. Then the number of macrophages was counted,
      and the macrophages were analyzed for their lactic dehydrogenase (LDH) activity,
      acid phosphatase (ACP) activity, phagocytic activity, secretion of nitric oxide
      (NO) and cytotoxicity. The number of peritoneal macrophages, the activity of LDH
      and ACP, phagocytic activity, NO secretion, and cytotoxicity were increased with
      the increasing doses of OK-432. The results suggested that OK-432 enhanced tumor
      cytotoxicity of peritoneal macrophages by three steps. The first step is to
      attract a great number of macrophages into the peritoneal cavity. The second step
      is to enhance the phagocytic and eliminating function of these macrophages. The
      last step is to increase the non-contact cytotoxicity of macrophages.

PMID- 11593061
TI  - INTRODUCTION.

PMID- 11593063
TI  - Pediatric heart failure management: solving the puzzle.

PMID- 11593064
TI  - Cellular and molecular aspects of myocardial dysfunction.
AB  - Disruption of any one of a large number of balanced systems that maintain
      cardiomyocyte structure and function can cause myocardial dysfunction. Such
      disruption can occur either in response to acute stresses such as cardiac surgery
      with cardiopulmonary bypass and cross-clamping of the aorta or because of more
      chronic stresses resulting from factors such as genetic abnormalities, infection,
      or chronic ischemia. Several currently available therapies such as beta
      adrenergic receptor agonists and antagonists, phosphodiesterase inhibitors,
      angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and
      other agents affect cardiomyocytes in ways that are more far reaching than
      initially appreciated when these agents were first introduced into clinical
      practice. As our knowledge and understanding of myocardial dysfunction increases,
      particularly in the neonatal and pediatric patient, we will be able to further
      target interventions to highly specific perturbations of cellular function and
      individual genetic variability.

PMID- 11593065
TI  - Managing low cardiac output syndrome after congenital heart surgery.

PMID- 11593066
TI  - Heart failure in pediatric septic shock: utilizing inotropic support.
AB  - Septic shock presents a unique challenge in the pediatric patient. Sepsis
      stimulates the release of inflammatory mediators that can compromise cardiac
      function. Oxygen extraction abnormalities, diminished responses to adrenergic
      agonists, and impaired ventricular function often result. After fluid
      resuscitation and antibiotic therapy, careful cardiovascular assessment is needed
      to administer appropriate inotropic and vasoactive drugs.

PMID- 11593067
TI  - Optimizing treatment for chronic congestive heart failure in children.
AB  - Treatment strategies for chronic heart failure in children have generally been
      extrapolated from studies in adults with heart failure. This presentation reviews
      the existing knowledge and recommendations regarding the treatment of chronic
      heart failure in adults and the information that is available in children.
      Medications currently recommended for use in adults include diuretics, digoxin,
      angiotensin-converting enzyme inhibitors, and beta-blockers. These
      recommendations are based on results from large, randomized, multicenter trials.
      Anecdotal evidence suggests similar beneficial effects of these medications in
      children. The fact that the etiologies, pathophysiology, and physiologic
      consequences of heart failure in children often differ greatly from those in
      adults, however, justifies the development of prospective, randomized trials to
      evaluate these medications specifically in children. Findings from these types of
      studies will provide critical information for developing guidelines for the
      appropriate treatment of children with chronic heart failure.

PMID- 11593069
TI  - Selective serotonin reuptake inhibitor antidepressants: cardiovascular
      complications--sorting through findings.

PMID- 11593070
TI  - Olanzapine as long-term adjunctive therapy in treatment-resistant bipolar
      disorder.
AB  - The aim of this study was to estimate the long-term effectiveness of olanzapine
      as adjunctive therapy in patients with bipolar disorder who exhibited an
      inadequate response to mood stabilizers. Twenty-three Research Diagnostic
      Criteria (RDC) patients with bipolar I and II were assessed by means of the
      Schedule for Affective Disorders and Schizophrenia and entered if they gave their
      consent to participate. All of them had experienced frequent relapses, residual
      subsyndromal symptoms, and inadequate responses to other drugs, such as lithium,
      valproate, or carbamazepine. While maintaining other drugs, they all received
      open-label, increasing doses of olanzapine, until achieving clinical response.
      Other drugs were maintained. The patients were assessed several consecutive times
      from baseline to the endpoint with the Clinical Global Impressions (CGI) scale
      for use in bipolar illness. Records of recurrences, hospitalizations, and side
      effects were also collected. The last-observation-carried-forward analysis showed
      that there was a significant reduction of CGI scores after the introduction of
      olanzapine, either in manic symptoms (p = 0.0015), depressive symptoms (p =
      0.0063), or global symptoms (p = 0.0003). The most frequent adverse events were
      somnolence (17%) and weight gain (13%). The mean dose of olanzapine at the end of
      the 43-week follow-up was 8.1 mg/day. Olanzapine may be a useful medication for
      the long-term adjunctive treatment of patients with bipolar disorder who exhibit
      a poor response to mood stabilizers, such as lithium, valproate, or
      carbamazepine. These results suggest mood-stablizing properties of olanzapine.

PMID- 11593071
TI  - Tolerability of combined treatment with lithium and paroxetine in patients with
      bipolar disorder and depression.
AB  - Patients with bipolar disorder are often prescribed lithium in combination with a
      selective serotonin reuptake inhibitor. Doubts still remain, however, about the
      safety of the combination, particularly with regard to the risk of developing a
      serotonin syndrome. The authors retrospectively evaluated the safety of the
      combination of lithium and paroxetine when the two medications were sequentially
      prescribed in patients with bipolar disorder. The authors examined a sample of 17
      patients with bipolar disorder who were treated with lithium during a depressive
      episode and who required paroxetine as an adjunctive antidepressant to ongoing
      lithium treatment. Averaging across all subjects, no statistically significant
      increase was found for any of the somatic symptoms that were assessed before and
      after paroxetine was added to ongoing lithium therapy. Examining the clinical
      records of each patient in detail; however, four patients who developed
      significant adverse events, possibly related to an emerging serotonin syndrome
      were identified. Clinicians should be aware of the possible development of a
      serotonin syndrome among patients in whom paroxetine is added to ongoing lithium
      treatment.

PMID- 11593072
TI  - Clozapine enhances neurocognition and clinical symptomatology more than standard
      neuroleptics.
AB  - Neurocognition and clinical symptomatology were evaluated in 27 patients with
      schizophrenia during a double-blind, placebo-controlled, cross-over study
      involving clozapine, an atypical antipsychotic agent, and haloperidol, a
      conventional neuroleptic. Patients were assessed 5 to 6 weeks after initiation of
      each phase. Clinical symptomatology, based on Brief Psychiatric Rating Scale and
      Scale for the Assessment of Negative Symptoms ratings, markedly improved after
      treatment with both haloperidol and clozapine. The beneficial effects of
      clozapine were statistically significantly greater than the effects from the
      haloperidol treatment. Regarding neurocognition, both agents proved efficacious
      in improving performance on nearly all measures compared with placebo. In
      addition, as compared with haloperidol, clozapine significantly improved
      performance on Trails B, Verbal Fluency, and measures of delayed verbal memory,
      and it tended to increase performance on most measures. Additional analyses
      indicated that the improvement on neurocognitive measures was not because of
      symptom amelioration; rather, neurocognitive deficits seem to be an intrinsic
      enduring feature of schizophrenia. The superiority of clozapine over haloperidol
      may be related to clozapine's unique psychopharmacologic profile.

PMID- 11593074
TI  - Clinical predictors of drug response in obsessive-compulsive disorder.
AB  - The aim of this study was to evaluate which clinical variables might influence
      the antiobsessional response to proserotonergic drugs in a sample of patients
      with obsessive-compulsive disorder (OCD). One hundred fifty-nine patients with
      DSM-IV OCD underwent a 12-week standardized treatment with fluvoxamine,
      clomipramine, citalopram, or paroxetine. According to treatment response, defined
      as a reduction of the Yale-Brown Obsessive Compulsive Scale total score >35%,
      patients were divided into two groups. Ninety patients (56.6%) responded to
      treatment and 69 (43.4%) did not. Responders had a significantly higher frequency
      of positive family history for OCD (FH-OCD) in their first-degree relatives,
      whereas nonresponders had an earlier onset and a higher frequency of "poor
      insight" subtype and somatic obsessions. The predictive value of all these
      variables was tested by a stepwise logistic regression analysis that confirmed
      poor insight and FH-OCD to be the best predictors of poor and good drug treatment
      response, respectively. These preliminary findings need additional investigations
      toward a better definition of the genetic and biological heterogeneity of
      patients with OCD, and they underlie the importance of collecting the insight
      score and family history for psychiatric disorders in the pretreatment
      assessment.

PMID- 11593073
TI  - A placebo-controlled pilot study of the ampakine CX516 added to clozapine in
      schizophrenia.
AB  - CX516, a positive modulator of the glutamatergic alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid receptor, improves performance in tasks
      requiring learning and memory in animals. CX516 was added to clozapine in 4-week,
      placebo-controlled, dose-finding (N = 6) and fixed-dose (N = 13) trials. CX516
      was tolerated well and was associated with moderate to large, between-group
      effect sizes compared with placebo, representing improvement in measures of
      attention and memory. These preliminary results suggest that CX516 and other
      "ampakines" hold promise for the treatment of schizophrenia.

PMID- 11593075
TI  - Lack of effect of citalopram on the steady-state pharmacokinetics of
      carbamazepine in healthy male subjects.
AB  - Carbamazepine, a drug used in the treatment of seizure disorders, and citalopram,
      a highly selective serotonin reuptake inhibitor used for the treatment of
      depression and other psychiatric disorders, are both metabolized predominantly by
      the cytochrome P4503A4 isozyme. In this study, the effect of subchronic
      administration of citalopram on the steady-state pharmacokinetics of
      carbamazepine was evaluated in 12 healthy male subjects. Carbamazepine was
      administered orally twice daily as a 100-mg dose from days 1 to 3, as a 200-mg
      dose twice a day from days 4 to 6, and as a 400-mg dose once a day from days 7 to
      35. Citalopram, 40 mg, administered once daily, was added to the carbamazepine
      dosing regimen on days 22 to 35. The steady-state plasma concentration profiles
      of carbamazepine and its active metabolite, carbamazepine 10,11-epoxide, on day
      35 (in the presence of steady-state levels of citalopram) were compared to the
      corresponding carbamazepine and epoxide metabolite profiles on day 21 (in the
      absence of citalopram). No significant differences were found between mean steady
      state values for maximal drug concentration, area under the curve, or time of
      maximal concentration values for carbamazepine and its epoxide metabolite before
      and after the addition of citalopram to the daily carbamazepine dosing regimen (p
      > 0.05). These results suggest that the use of citalopram in patients stabilized
      on carbamazepine should not produce clinically significant changes in
      carbamazepine plasma concentrations.

PMID- 11593076
TI  - Drug glucuronidation in clinical psychopharmacology.
AB  - Glucuronidation is a phase II metabolic process and one of the most common
      pathways in the formation of hydrophilic drug metabolites. At least 33 families
      of uridine diphosphate-glucuronosyltransferases have been identified in vitro,
      and specific nomenclature similar to that used to classify the cytochrome (CYP)
      P450 system has been established. The UGT1 and UGT2 subfamilies represent the
      most important of these enzymes in human drug metabolism. Factors affecting
      glucuronidation include the following: cigarette smoking, obesity, age, and
      gender. In addition, several drugs have been found in vitro to be substrates,
      inhibitors, or inducers of UGT enzymes. Induction or inhibition of both UGT and
      CYP isoforms may occur simultaneously. Some important drug interactions involving
      glucuronidation have been documented and others can be postulated. This review
      summarizes the relevant literature pertaining to drug glucuronidation and its
      implications for clinical psychopharmacology.

PMID- 11593077
TI  - Rapid reversal of psychotic depression using mifepristone.
AB  - The rationale for treating psychotic major depression with glucocorticoid
      receptor (GR) antagonists is reviewed. Five patients with psychotic major
      depression were given 600 mg of mifepristone in a 4-day, double-blind, placebo
      controlled crossover study. All the patients completed the protocol and adverse
      effects were not observed or reported. All of the five patients showed
      substantial improvements in their Hamilton Rating Scale for Depression scores
      while they were receiving mifepristone, and four of the five patients showed
      substantial improvement in their Brief Psychiatric Rating Scale scores. Little,
      if any, improvement was seen with placebo. These preliminary results suggest that
      short-term use of GR antagonists may be effective in the treatment of psychotic
      major depression and that additional study, perhaps using higher doses or more
      treatment days, seems warranted.

PMID- 11593078
TI  - Dextroamphetamine for cocaine-dependence treatment: a double-blind randomized
      clinical trial.
AB  - A properly implemented agonist treatment regimen should improve retention and
      reduce illicit drug use. Cocaine-dependent subjects (N = 128) were enrolled in a
      12-week randomized, double-blind, placebo-controlled trial. In the multistage
      dosing design, subjects initially received placebo (PBO) or 15 to 30 mg of
      dextroamphetamine sulfate, sustained-release capsules. At week 5, the dose
      doubled to 30 mg or 60 mg for active groups. Subjects attended the clinic twice a
      week, provided urine samples, obtained medication, and had one behavioral therapy
      session a week. Retention was best for the 15- to 30-mg group, whereas the
      proportion of benzoylecgonine-positive urine screens was, from lowest to highest,
      30 to 60 mg, 15 to 30 mg, and PBO at study end. Dosing must be refined. The
      results provide support for additional examination of the agonist model in
      psychostimulant-dependence treatment.

PMID- 11593079
TI  - Cognitive improvements in psychotic subjects treated with "Seroquel" (quetiapine
      fumarate): an exploratory study.

PMID- 11593080
TI  - Pancreatitis and cholestatic hepatitis induced by risperidone.

PMID- 11593081
TI  - St. John's wort: effect on CYP2D6 activity using dextromethorphan-dextrorphan
      ratios.

PMID- 11593082
TI  - Predictors of sertraline discontinuation syndrome in anorexia nervosa.

PMID- 11593083
TI  - A case of ginseng-induced mania.

PMID- 11593084
TI  - Mirtazapine treatment of obsessive-compulsive disorder.

PMID- 11593085
TI  - Anxiolytic effects of vigabatrin in panic disorder.

PMID- 11593086
TI  - Concurrent use of oral contraceptives with antidepressants for premenstrual
      syndromes.

PMID- 11593087
TI  - Time versus frequency domain techniques for assessing baroreflex sensitivity.
AB  - BACKGROUND: Newer techniques to evaluate baroreflex sensitivity (BRS) are based
      on the analysis of blood pressure (BP) and heart rate (HR) time series in the
      time or frequency domain. These novel approaches are steadily gaining popularity,
      since they do not require injection of vasoactive substances, nor do they rely on
      a complex experimental set-up. AIM: This review outlines and compares some basic
      features of the latest methods to assess spontaneous baroreflex function.
      RESULTS: Modern techniques for the estimation of spontaneous BRS are based on a
      variety of signal processing schemes and derive information on the baroreflex
      function from different perspectives. Thus factors such as respiration and other
      non-stationary agents may have different influences on the estimates provided by
      each of these approaches. Notwithstanding such individual specificity, however,
      it has been observed that in several physiological and pathophysiological
      conditions these techniques often provide comparable information on BRS changes
      over time, particularly when the estimates are averaged over time windows of a
      few minutes. CONCLUSIONS: Due to the general agreement in the pattern of BRS
      among most modern methods, it seems reasonable to employ the most validated of
      these techniques, for which data obtained in several studies are already
      available.

PMID- 11593088
TI  - Sympathetic modulation of blood pressure variability.
AB  - Although sympathetic nervous activity (SNA) displays oscillations synchronous
      with the heart beat and respiration, and between 0.1-0.4 Hz, it is apparent that
      each of these frequencies does not have the same effect on the vasculature.
      Frequencies above 1 Hz do not produce oscillations in the vasculature but instead
      contribute to the mean level of vasoconstriction. Slower oscillations in SNA
      result in a cycle of vasoconstriction and vasodilation within the vasculature,
      the amplitude of which, generally decreases with increasing frequency. Some
      studies indicate that, within the same species, differences exist in the
      frequency responses between vascular beds, such as the skin and gut. This
      differential responsiveness is also found between the medullary and cortical
      vasculature regions of the rabbit kidney. Low-pass filter properties have been
      described in the iliac circulation of rats, and evidence has been provided that
      noradrenaline reuptake mechanisms are not the frequency limiting step of the
      vasculature response. Recent studies on isolated rat vascular smooth muscle cells
      suggest that sympathetic modulation of vascular tone is limited by the alpha
      adrenoceptor signal transduction into the cells and not by an intrinsic inability
      of the cells to contract and relax at higher rates.

PMID- 11593089
TI  - Renin-angiotensin-sympathetic crosstalks in hypertension: reappraising the
      relevance of peripheral interactions.

PMID- 11593090
TI  - Hypertension in South African adults: results from the Demographic and Health
      Survey, 1998.
AB  - OBJECTIVES: To determine the prevalence and treatment status of hypertension in
      South Africa. DESIGN: National cross-sectional survey. SETTING: 13 802 randomly
      selected South Africans, 15 years and older, were visited in their homes in 1998.
      METHODS: Trained fieldworkers completed questionnaires on lifestyle and chronic
      diseases, measured blood pressure with an Omron manometer and recorded chronic
      drug utilization. Drugs were classified using the Anatomical Therapeutic Chemical
      index. RESULTS: The mean systolic blood pressure for men and women was 123 mmHg
      (SE 0.37) and 119 mmHg (SE 0.36), while the mean diastolic level was 76 mmHg (SE
      0.25) and 75 mmHg (SE 0.20), respectively. When using a cut-off point of 140/90
      mmHg the hypertension prevalence rate (age-adjusted to the South African
      Population, Census 1996) was 21% for both genders. Using the current cut-off
      point (160/95 mmHg) for South Africa, the prevalence rate was 11% for men and 14%
      for women. For men with hypertension, the level of awareness, taking
      antihypertensive medication and having controlled blood pressure (< 160/95 mmHg)
      were 41, 39 and 26% respectively, while for women these rates were 67, 55 and 38%
      respectively. CONCLUSIONS: This survey revealed high levels of hypertension in
      the South African community with inadequate treatment status.

PMID- 11593091
TI  - High blood pressure and associated cardiovascular risk factors in France.
AB  - OBJECTIVE: To estimate, with respect to age and gender, the prevalence of high
      blood pressure (BP) in treated and non-treated subjects and its association with
      other cardiovascular risk factors. DESIGN: A cross-sectional study. SETTING:
      Healthcare centres in the centre of France. PARTICIPANTS: All subjects (n =
      61,108) who had a free health check-up, between February 1995 and September 1996.
      MAIN OUTCOME MEASURES: High BP (systolic blood pressure (SBP) > 140 mmHg,
      diastolic blood pressure (DBP) > 90 mmHg or antihypertensive therapy); diabetes
      (fasting glucose plasma concentration > 1.26 g/l or antidiabetic therapy);
      hypercholesterolaemia (total cholesterol > 2 g/l or lipid-lowering therapy);
      hypertriglyceridaemia (fasting triglycerides plasma concentration > 2 g/l or
      triglyceridaemia-lowering therapy); overweight (body mass index >or= 25 kg/m2);
      abdominal fat distribution (waist to hip ratio > 0.9 in males and > 0.8 in
      females). RESULTS: Prevalence of high BP was 37.7% in males and 22.2% in females.
      BP was normalized in 29.7% of treated males and 44.1% of treated females. High BP
      was associated with at least another cardiovascular risk factor in 83.8% of the
      males and 76.7% of the females with high BP. Hypercholesterolaemia was the most
      frequently associated risk factor. Except smoking, the prevalence of each
      cardiovascular risk factor was shown to increase with the severity of
      hypertension. Two or more other cardiovascular risk factors were present in 22.9%
      of the males and 9.8% of the females with high BP. CONCLUSIONS: Rate of high BP,
      even in treated subjects, is high. More than three out of four subjects with high
      BP have at least one other cardiovascular risk factor.

PMID- 11593092
TI  - Long-term effects of exercise on blood pressure and lipids in healthy women aged
      40-65 years: The Sedentary Women Exercise Adherence Trial (SWEAT).
AB  - OBJECTIVES: To evaluate the long-term effects of regular moderate or vigorous
      intensity exercise on blood pressure and blood lipids in previously sedentary
      older women. DESIGN: Subjects were randomly assigned to either a supervised
      centre-based (CB) or a minimally supervised home-based (HB) exercise program,
      initially for 6 months. Within each program, subjects were further randomized to
      exercise either at moderate (40-55% heart rate reserve, HRres) or vigorous
      intensity (65-80% HRres). After 6 months, all groups continued a HB moderate or
      vigorous exercise program for another 12 months. METHODS: Healthy, sedentary
      women (aged 40-65 years) (n = 126) were recruited from the community. Subjects
      exercised three times per week for 30 min. They were evaluated at baseline, 6, 12
      and 18 months. RESULTS: There was a significant fall of 2.81 mmHg in systolic
      blood pressure (P = 0.049) and 2.70 mmHg in diastolic blood pressure (P = 0.004)
      after correction for age and baseline values with moderate exercise, but not with
      vigorous-intensity exercise. When this analysis was repeated with the change in
      body mass included, the results were unchanged. After correction for potential
      confounding factors, there was a significant fall in total cholesterol and low
      density lipoprotein cholesterol with vigorous but not moderate exercise at 6
      months (P < 0.05) but not at 18 months. CONCLUSIONS: In this largely normotensive
      population of older women, a moderate, but not vigorous exercise program,
      achieved sustained falls in resting systolic and diastolic blood pressure over 18
      months. The study demonstrates that, in older women, moderate intensity exercise
      is well accepted, sustainable long-term and has the health benefit of reduced
      blood pressure.

PMID- 11593093
TI  - Role of weight loss and polyunsaturated fatty acids in improving metabolic
      fitness in moderately obese, moderately hypertensive subjects.
AB  - OBJECTIVE: While the exact regulatory interactions between blood pressure (BP)
      and obesity are not completely understood, weight loss provides an alternative to
      pharmacological treatment of hypertension. The intent of this repeated measures
      study of mild-moderate hypertensive, moderately obese subjects (34 females/18
      males) was to determine if the reduction in BP following weight loss could be
      further affected by modifying the fatty acid (FA) composition of the hypocaloric
      diet. METHODS: BP, insulin sensitivity (Si), and lipid parameters were assessed
      before and after a 10-week calorie-restricted period. Subjects were randomized to
      one of three dietary groups differing in FA composition. Reduced body weight was
      maintained for a further 4 weeks and body composition assessment, BP and heart
      rate measurements were repeated. RESULTS: Weight loss (10%) in obese hypertensive
      subjects resulted in substantial improvements in BP, Si and lipid profile. There
      was no additional effect on the reduction in BP by the type of FA consumed in the
      diet. Following weight loss, there was a trend for omega-3 FAs to have a
      protective effect on fat-free mass loss (compared to omega-6 FA Group and
      saturated FA Group) and a trend to further enhance Si. There were significant
      improvements in circulating lipid profiles independent of the dietary FA
      intervention following the weight loss. The improvements in BP and body
      composition were maintained during the weight-loss maintenance period. The type
      of fat consumed had minor differential effects on some of the measured metabolic
      outcomes. CONCLUSION: These results provide strong support for modest weight loss
      as a treatment for hypertension.

PMID- 11593094
TI  - Twenty-four hour ambulatory blood pressure in the Hypertension Optimal Treatment
      (HOT) study.
AB  - BACKGROUND AND AIMS: The Hypertension Optimal Treatment (HOT) study showed that
      when antihypertensive treatment reduces diastolic blood pressure well below 90
      mmHg, there can be a further reduction of cardiovascular events, particularly
      myocardial infarction, with no evidence of a J-shaped curve at lower pressures.
      Office measurement, however, gives no information about blood pressure outside
      the office. This paper describes a HOT substudy in which patients underwent both
      office measurement and 24 h ambulatory blood pressure monitoring. METHODS: The
      mean age of the substudy population was 62 +/- 7 years. Substudy patients were
      treated for a median period of 2 years. All received the dihydropyridine calcium
      antagonist felodipine, while some also received an ACE-inhibitor, a beta-blocker
      or a diuretic. Average 24 h, day and night ambulatory blood pressure values were
      computed at baseline (n = 277) and during treatment (n = 347): 112 patients had
      been randomized to a target office diastolic blood pressure <or= 90 mmHg, 117 to
      <or= 85 mmHg and 118 to <or= 80 mmHg. Additional analyses included computation
      of: (1) trough-to-peak ratio and (2) the smoothness index (the ratio between the
      average of the 24 hourly blood pressure reductions after treatment and its
      standard deviation). RESULTS: Taking the subgroup as a whole, baseline 24 h
      average blood pressures (146 +/- 18/90 +/- 10 mmHg) were significantly and
      markedly lower than office blood pressures (170 +/- 14/105 +/- 3 mmHg, P < 0.01).
      Office, 24 h, day and night blood pressures were all significantly reduced by
      treatment, but there was a smaller fall in ambulatory, than in office pressures.
      The between group differences in office blood pressure were smaller than those
      observed in the overall HOT sample. Between-group differences in 24 h blood
      pressure were even smaller. Trough-to-peak ratios and smoothness indices were
      lowest in the highest blood pressure target group and highest in the lowest blood
      pressure target group. Office and ambulatory blood pressures were similar in the
      groups randomized to placebo (n = 170) or acetylsalicylic acid (n = 177).
      CONCLUSION: In conclusion, in the HOT study, treatment reduced not only office
      but also ambulatory blood pressure throughout the 24 h. The reduction was less
      marked for ambulatory than for office blood pressure.

PMID- 11593095
TI  - The influence of the method of data analysis on the reported accuracy of
      automated blood pressure measuring devices.
AB  - OBJECTIVE: To show that different methods of data analysis affect the grading
      that blood pressure measuring devices achieve according to the British
      Hypertension Society (BHS)-protocol. METHODS: Based on the somewhat unclear
      description of the exact method of data analysis in the BHS-protocol four
      different methods can be discerned. The effect on the grading-results is
      calculated for these four different options. RESULTS AND CONCLUSIONS: It is shown
      that using these four different options the achieved grade can range for
      diastolic blood pressure from C (option 1) to almost A (option 4) and for
      systolic blood pressure from D (option 1) to B (option 4). Different researchers
      may well have used different methods. Option 1 is the method that should be used.
      Also it is stated that the systematic error and the standard deviation of
      differences (SDD) are measures that give more insight to describe a device's
      performance. Calculating the grades after correction for the systematic error
      shows its influence and that of the SDD on the reported accuracy of a blood
      pressure measuring device.

PMID- 11593096
TI  - Tyrosine hydroxylase antisense gene therapy causes hypotensive effects in the
      spontaneously hypertensive rats.
AB  - We investigated the effect of antisense oligodeoxynucleotides (AS ODN) against
      tyrosine hydroxylase (TH) on hypertension and sympathetic nervous system activity
      in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) in SHR
      treated with TH AS ODN (50, 200 microg/rat, i.v.) was significantly lower than
      that of control SHR. Epinephrine and norepinephrine levels, TH activity, and TH
      protein levels in the adrenal medulla of SHR were reduced concomitant with TH AS
      ODN treatment-induced changes in SBP. In contrast, TH AS ODN (200 microg/rat) had
      no effect on SBP in Wistar-Kyoto rats (WKY), despite significantly decreased
      catecholamine levels, TH activity, and TH protein levels. These findings suggest
      that peripheral systemic injection of TH AS ODN may be effective as hypotensive
      therapy in SHR.

PMID- 11593097
TI  - Association between the endothelin-1 gene Lys198Asn polymorphism blood pressure
      and plasma endothelin-1 levels in normal and pre-eclamptic pregnancy.
AB  - OBJECTIVE: This study examined the frequency of the Lys198Asn polymorphism in the
      endothelin-1 (ET-1) gene in women with pre-eclampsia and normal pregnancy; and
      its contribution to levels of plasma ET-1 and blood pressure. DESIGN AND METHODS:
      This was a retrospective study examining the frequency of the ET-1 Lys198Asn
      polymorphism in 72 proteinuric pre-eclamptics and 81 normal pregnant women.
      Height, weight, blood pressure and plasma ET-1 were measured antenatally and at 6
      weeks post-partum. Using specific mutagenic primers, the frequency of the G/G
      (normal), G/T heterozygote and T/T (mutant) genotypes of the Lys198Asn
      polymorphism were examined. RESULTS: The polymorphism was not associated with pre
      eclampsia. However, in the combined pregnant groups after correction for BMI and
      group, a significant effect of the T-allele (T/T,G/T) on systolic blood pressure
      was found (121 +/- 1.5 mmHg compared with 116 +/- 1.3 mmHg in the G/G
      homozygotes). A significant interaction was found between the T-allele and
      pregnancy in determining systolic blood pressure, so that the effect was no
      longer seen post-partum. Pregnant women with the T/T genotype had significantly
      elevated plasma ET-1 levels 5.8 pg/ml [confidence interval (CI) 3.7-9.1] compared
      with 3.1 pg/ml (CI 2.6-3.8) in the G/T heterozygotes and 3.6 pg/ml (CI 3.0-4.1)
      in the normal G/G homozygotes. CONCLUSION: The Lys198Asn polymorphism does not
      directly contribute to the incidence of pre-eclampsia. However, the association
      of the T-allele with raised blood pressure and the T/T genotype with increased
      plasma ET-1 levels suggest that this polymorphism may interact with other genes
      or environmental factors to sensitize pregnant women to develop pre-eclampsia.

PMID- 11593098
TI  - Angiotensin converting enzyme gene polymorphism predicts blood pressure response
      to angiotensin II receptor type 1 antagonist treatment in hypertensive patients.
AB  - OBJECTIVES: To determine whether polymorphisms in the renin-angiotensin system
      can predict blood pressure-lowering response to antihypertensive treatment; more
      specifically, in response to treatment with irbesartan or atenolol. DESIGN AND
      METHODS: Eighty-six patients with hypertension were randomized to double-blind
      treatment with either the angiotensin II type 1 receptor antagonist irbesartan or
      the beta1 adrenergic receptor blocker atenolol and followed for 3 months. We
      analysed angiotensinogen T174M and M235T, angiotensin converting enzyme (ACE) I/D
      and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood
      pressure reduction. RESULTS: The mean reductions in blood pressure were similar
      for both treatments. In the irbesartan group, individuals homozygous for the ACE
      gene I allele showed a greater reduction in diastolic blood pressure, exceeding
      those with the D allele (-18 +/- 11 SD versus -7 +/- 10 mmHg, P = 0.0096). This
      was not the case during treatment with atenolol, and the interaction term between
      type of treatment and ACE II genotype was significant (P = 0.0176). The
      angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related
      to the response to treatment. CONCLUSIONS: ACE genotyping predicted the blood
      pressure-lowering response to antihypertensive treatment with irbesartan but not
      atenolol. Thus, specific genotypes might predict the response to specific
      antihypertensive treatment.

PMID- 11593099
TI  - Effects of ET(A) - and ET(B)-receptor antagonists on regional kidney blood flow,
      and responses to intravenous endothelin-1, in anaesthetized rabbits.
AB  - OBJECTIVE: To determine the roles of endothelin (ET)-receptor subtypes in the
      effects of exogenous and endogenous ETs on regional kidney blood flow in
      anaesthetized rabbits. DESIGN AND METHODS: The effects on regional kidney blood
      flow of the ET(A) antagonist BQ610, and the ET(B) antagonist BQ788, were tested.
      We also examined the effects of intravenous and renal arterial bolus doses of ET
      1, and how these responses are modified by pretreatment with BQ610 and BQ788.
      RESULTS: BQ610 reduced mean arterial pressure (MAP, 3%), and increased total
      renal blood flow (RBF, 10%), cortical perfusion (CBF, 11%) and medullary
      perfusion (MBF, 16%). BQ788 increased MAP (6%) and reduced RBF (16%) and CBF
      (13%) but not MBF. The effects of BQ788 were abolished by pretreatment with
      BQ610. Intravenous ET-1 (300 ng/kg) reduced RBF and CBF, but increased MBF. BQ788
      potentiated ET-1 mediated reductions in CBF, and abolished increases in MBF.
      BQ610 blunted reductions in RBF and CBF produced by ET-1, but did not
      significantly affect MBF responses. The renal vascular effects of intravenous ET
      1 were mimicked by lower doses (1-30 ng/kg) administered into the renal artery.
      CONCLUSIONS: Endogenous ETs act at ET(A)-receptors to reduce MBF and CBF, but
      ET(B)-receptors have little direct role in physiological control of renal
      haemodynamics. Bolus doses of ET-1 act at ET(B)-receptors in the kidney to
      increase MBF. The effects of bolus ET-1 on the cortical vasculature appear to
      result from the competing influences of ET(A)-mediated vasoconstriction and ET(B)
      mediated vasodilatation.

PMID- 11593100
TI  - Transient involvement of endothelin in hypertrophic remodeling of small arteries.
AB  - OBJECTIVE: This study was designed to evaluate the capacity of norepinephrine
      (NE) to induce hypertrophic remodeling of small arteries in rats, and to
      determine the involvement of endothelin (ET) to initiate and maintain it. DESIGN
      AND RESULTS: Treatment with NE (2.5 microg/kg per min) for 14 or 28 days produced
      a similar inward hypertrophic remodeling, characterized by a smaller lumen, but
      increased media thickness and cross-sectional area. Arterial stiffness was
      reduced. Histological evaluation confirmed the hypertrophic nature of remodeling.
      Concomitant administration of LU135252 (ET-receptor antagonist) for the first 14
      days of NE administration prevented the development of hypertrophy, without
      altering arterial mechanics. Treatment with the same antagonist from day 14 to
      day 28 of NE or angiotensin II (Ang II) treatment failed to regress established
      vascular hypertrophy. In contrast, normalization of arterial structure was
      observed with prazosin, an alpha-adrenergic blocker. Endothelin content in small
      mesenteric arteries showed a transient elevation following chronic NE
      administration. CONCLUSIONS: Increased circulating NE levels are associated with
      hypertrophic remodeling of small arteries, in which ET plays an initiating role.
      However, the maintenance of vascular hypertrophy is ET-independent, either in the
      presence of augmented circulating levels of NE or Ang II. Thus, early rather than
      late treatment with ET-receptor antagonists may be a preferable approach to limit
      small artery-mediated end-organ damage in cardiovascular diseases.

PMID- 11593101
TI  - Treatment with irbesartan or atenolol improves endothelial function in essential
      hypertension.
AB  - OBJECTIVES: To investigate if antihypertensive treatment could improve
      endothelium-dependent vasodilatation in hypertensive patients, and whether the
      angiotensin II subtype-1 (AT1)-receptor antagonist irbesartan and the beta1
      receptor antagonist atenolol would differ in this respect. SUBJECTS AND METHODS:
      Thirty-four patients (28 men and six women) with mild-to-moderate essential
      hypertension (diastolic blood pressure 90-120 mmHg) were randomized to once daily
      150-300 mg irbesartan or 50-100 mg atenolol in a double-blind fashion, preceded
      by a placebo run-in period. Forearm blood flow (FBF) was assessed by venous
      occlusion plethysmography during local intra-arterial infusions of methacholine
      and sodium nitroprusside, to evaluate endothelium-dependent and endothelium
      independent vasodilatation, respectively. Measurements of FBF were undertaken at
      the end of the run-in placebo period and repeated after 3 months of active
      antihypertensive treatment. RESULTS: Irbesartan and atenolol induced a similar
      decline in blood pressure (from 171/107 to 158/98 mmHg, P < 0.05), and improved
      endothelium-dependent vasodilatation (e.g. an increase in FBF response to 4
      microg/min methacholine from 325 +/- 29% to 411 +/- 41%, P < 0.05), with no
      difference between the two study drugs. No significant changes in endothelium
      independent vasodilatation were induced by irbesartan or by atenolol.
      CONCLUSIONS: The present study shows that 3 months of antihypertensive therapy
      with irbesartan or atenolol improves endothelium-dependent vasodilatation.

PMID- 11593102
TI  - The impaired glutathione system and its up-regulation by sulforaphane in vascular
      smooth muscle cells from spontaneously hypertensive rats.
AB  - The glutathione (GSH) system plays an important role in reducing oxidative
      stress, the increase of which has been linked to the pathogenesis of
      hypertension. The aims of this study were to investigate: (1) whether the GSH
      system was impaired in aortic smooth muscle cells (SMCs) from spontaneously
      hypertensive rats (SHR), and (2) whether this system could be up-regulated by the
      phase-2 enzyme inducers, sulforaphane and t-butylhydroquinone (t-BHQ). Basal
      levels of cellular GSH, GSH-reductase and GSH-peroxidase were significantly lower
      in SMCs from SHR than from normotensive Wistar-Kyoto (WKY) rats. Heme oxygenase-1
      (HO-1) was significantly higher in SHR SMCs, which correlated with the higher
      oxidative stress experienced by these cells. No differences were observed in the
      basal activity of GSH-S-transferase nor in the ability to synthesize GSH between
      SMCs from these two strains. Sulforaphane (0.05-1 micromol/l) and t-BHQ (10-100
      micromol/l) induced significant and concentration-dependent increases in cellular
      GSH levels, HO-1 protein content and activities of GSH-reductase and GSH
      peroxidase in SMCs from both rat strains. Upregulation of phase 2 enzymes
      correlated with a decrease in oxidative stress experienced by the SMCs,
      particularly with SHR. We conclude that SHR SMCs experience greater oxidative
      stress than WKY SMCs and that malfunction of the GSH system contributes to the
      enhanced oxidative stress in SHR SMCs.

PMID- 11593103
TI  - Angiotensin converting enzyme inhibition improves cardiac neuronal uptake of
      noradrenaline in spontaneously hypertensive rats.
AB  - OBJECTIVES: It has been shown that a diminished sympathetic activity contributes
      to the hypotensive and cardioprotective actions of angiotensin converting enzyme
      (ACE) inhibitors (ACEI). Besides an inhibition of central sympathetic tone and
      peripheral noradrenaline release, we hypothesized that the interactions of ACEI
      with the sympathetic system may include a modulation of neuronal catecholamine
      uptake by peripheral nerves. DESIGN: We investigated the influence of fosinopril
      on noradrenergic uptake into cardiac neurones in vitro and in vivo in acute and
      chronic models. METHODS AND RESULTS: Acute administration of fosinoprilat to
      isolated perfused rat hearts increased the extraction of [3H]-noradrenaline from
      the perfusate by 39%. Treatment (14 days) of spontaneously hypertensive rats
      (SHR) with fosinopril (20 mg/kg per day) enhanced the cardiac uptake of i.v.
      administered [3H]-noradrenaline by 28%. The endogenous left ventricular content
      of noradrenaline was increased by 49% after an antihypertensive treatment of SHR
      with fosinopril (20 mg/kg per day). Identical increases in cardiac noradrenaline
      stores (53%) were observed in SHR treated with a blood pressure ineffective dose
      of fosinopril (0.2 mg/kg per day). The myocardial content of adrenaline was
      increased in parallel to noradrenaline after both dose regimes. CONCLUSIONS: It
      is concluded that ACEI increases neuronal uptake of catecholamines in SHR in a
      blood pressure-independent manner. This effect occurs acutely and is independent
      of central sympathetic activity. Therefore, we hypothesize that ACEI modulate the
      activity of the cardiac noradrenaline transporter by direct activation. The
      improved uptake of noradrenaline may contribute to the antihypertensive and
      cardioprotective effects of ACEI.

PMID- 11593104
TI  - Inhibitory effect of the angiotensin converting enzyme inhibitors captopril and
      enalapril on the conversion of procollagen to collagen.
AB  - OBJECTIVE AND DESIGN: Angiotensin converting enzyme inhibitors are reported to
      inhibit the collagen accumulation involved in left ventricular hypertrophy. We
      tested the effect of captopril and enalapril on the conversion of procollagen to
      collagen in short-term tissue cultures in order to study the possible mechanisms
      by which the antifibrotic effect of this group of inhibitors takes place.
      METHODS: We employed short-term cartilage and tendon tissue cultures to monitor
      the conversion of procollagen to collagen. After pulse-labelling with [14C]
      proline, the cultures were incubated further with the test compounds in different
      concentrations for a 180 min chase period. The reaction was stopped and
      radioactive collagenous peptides were analysed by gel electrophoresis. The
      amounts of collagenous proalpha and alpha chains were estimated, and the
      inhibition of procollagen to collagen conversion was calculated relative to 0 min
      control (100% inhibition) and 180 min control (0% inhibition) samples. RESULTS:
      Inhibition (50%) was obtained with 7 mmol/l captopril and 22 mmol/l enalapril in
      the cartilage cultures. Both compounds seemed to inhibit the conversion in
      clearly lower concentrations in tendon cultures, 4 mmol/l and 7 mmol/l,
      respectively, were sufficient for 50% inhibition. Angiotensin I, II, saralasin
      and bradykinin did not have any effect on conversion at 3.5, 9, 2 and 4 mmol/l
      concentrations, respectively. CONCLUSION: The peptidase inhibitors captopril and
      enalapril are able to inhibit the conversion of procollagen to collagen, which is
      a proteolytic process, possibly by inhibiting the specific procollagen proteases.
      Whether this phenomenon is involved in the antifibrotic property of angiotensin
      converting enzyme inhibitors warrants further study, as does the question of
      whether new antifibrotic agents could be developed on this basis.

PMID- 11593105
TI  - Role of AT1 and AT2 receptor subtypes in salt-sensitive hypertension induced by
      sensory nerve degeneration.
AB  - OBJECTIVE: To define the role of the type 1 angiotensin II (AT1) and type II
      (AT2) receptors in the development of salt-sensitive hypertension induced by
      sensory nerve degeneration. DESIGN AND METHODS: Neonatal Wistar rats were given
      capsaicin 50 mg/kg s.c. on the first and second days of life. After weaning, male
      rats were divided into six groups and treated for 3 weeks with: control + high
      sodium diet (4%, CON-HS), capsaicin pretreatment + normal sodium diet (0.5%, CAP
      NS), CAP-HS, CAP + HS + candesartan (10 mg/kg per day) (CAP-HS-CAN), CAP + HS +
      PD 123319 (30 mg/kg per day) (CAP-HS-PD), and capsaicin pretreatment + high
      sodium diet + candesartan + PD 123319 (CAP-HS-CAN-PD). Mean arterial pressure
      (MAP) was measured by carotid arterial catheterization. Urinary Na+
      concentrations were determined by using a flame atomic absorption
      spectrophotometer. Levels of calcitonin gene-related peptide (CGRP) in dorsal
      root ganglia (DRG) and plasma renin activity (PRA) were determined by
      radioimmunoassay. RESULTS: CGRP contents in DRG were decreased by capsaicin (P <
      0.05). MAP was higher in CAP-HS rats compared with all the other groups (P <
      0.05). The 24 h urine and sodium excretion increased when a high salt diet was
      given, but they were lower in CAP-HS and CAP-HS-CAN than in CON-HS (P < 0.05).
      PRA was suppressed in CON-HS and CAP-HS compared with CAP-NS, but it was higher
      in CAP-HS than in CON-HS (P < 0.05). CONCLUSION: Insufficiently suppressed PRA by
      high salt intake may contribute to increased salt sensitivity and account for
      effectiveness of candesartan in lowering blood pressure in this model.
      Furthermore, PD 123319 attenuates the development of hypertension in salt-loaded
      rats neonatally treated with capsaicin, indicating that the AT2 receptor
      contributes to the increase in blood pressure.

PMID- 11593106
TI  - Alpha1-adrenergic receptor subtypes in peripheral blood lymphocytes of essential
      hypertensives.
AB  - OBJECTIVE: The expression of alpha1-adrenergic receptor subtypes in peripheral
      blood lymphocytes was investigated in 28 essential hypertensive patients as well
      as in the peripheral blood lymphocytes and aorta of spontaneously hypertensive
      rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. METHODS: Alpha1-adrenergic
      receptors were quantified by radioligand binding assays, employing [3H]-prazosin
      as the radioligand in association with compounds displaying different degrees of
      selectivity for alpha1A-, alpha1B- and alpha1D-adrenergic receptor subtypes.
      RESULTS: The affinity of [3H]-prazosin binding was similar in peripheral blood
      lymphocytes of different stage essential hypertensive and normotensive subjects
      or of SHR and age-matched normotensive WKY rats as well as in the aortas of SHR
      and WKY rats. The radioligand binding assay revealed no change in the expression
      of alpha1-adrenergic receptors in peripheral blood lymphocytes of essential
      hypertensives compared with normotensive subjects; a moderate decrease of alpha1B
      adrenergic receptors and an increase of alpha1D-adrenergic receptors. The
      relative densities of the alpha1-adrenergic receptor subtypes were similar in the
      three groups of essential hypertensives. In peripheral blood lymphocytes and in
      aorta of SHR, [3H]-prazosin binding was significantly reduced compared with
      normotensive WKY rats. The expression of alpha1-adrenergic receptor subtypes in
      peripheral blood lymphocytes of SHR was similar to that found in peripheral blood
      lymphocytes of essential hypertensives. CONCLUSIONS: Changes of lymphocyte alpha1
      adrenergic receptor subtypes in essential hypertensives are similar to those
      observed in lymphocytes and vascular tissues of animal models of hypertension.
      This suggests that assays of lymphocyte alpha1-adrenergic receptors may represent
      an indirect marker of their involvement in essential hypertension.

PMID- 11593107
TI  - Comparative effects of losartan and irbesartan on serum uric acid in hypertensive
      patients with hyperuricaemia and gout.
AB  - OBJECTIVE: Losartan has been shown to increase urinary uric acid excretion and
      hence to lower serum uric acid levels. The purposes of the present study were:
      (1) to evaluate the effects of losartan on serum uric acid in hypertensive
      patients with hyperuricemia and gout, (2) to compare the effects of losartan with
      those of irbesartan, another angiotensin II receptor antagonist and (3) to
      evaluate whether losartan 50 mg b.i.d. has a greater impact on serum uric acid
      levels than losartan 50 mg once a day. METHODS: Thirteen hypertensive patients
      with hyperuricaemia and gout completed this prospective, randomized, double
      blind, cross-over study. Uric acid-lowering drugs were stopped 3 weeks before the
      beginning of the study. Patients were randomized to receive either losartan 50 mg
      or irbesartan 150 mg once a day, for 4 weeks. During this phase, a placebo was
      given in the evening. After 4 weeks, the dose was increased to losartan 50 mg
      b.i.d., or irbesartan 150 mg b.i.d. for another 4 week period. Subsequently, the
      patients were switched to the alternative treatment modality. Enalapril (20 mg
      o.d.) was given during the run-in period and between the two treatment phases.
      Serum and urinary uric acid were measured at the beginning and at the end of each
      treatment phase. RESULTS: Our results show that losartan 50 mg once daily
      decreased serum uric acid levels from 538 +/- 26 to 491 +/- 20 micromol/l (P <
      0.01). Irbesartan had no effect on serum uric acid. Increasing the dose of
      losartan from 50 mg o.d. to 50 mg twice a day, did not further decrease serum
      uric acid. This may in part be due to a low compliance to the evening dose as
      measured with an electronic device. Indeed, whatever the prescribed drug, the
      mean compliance of the evening dose was always significantly lower than that of
      the morning dose. The uricosuric effect of losartan appears to decrease with time
      when a new steady state of lower serum uric acid is reached. CONCLUSIONS: In
      contrast to irbesartan, losartan was uricosuric and decreased serum uric acid
      levels. Losartan 50 mg b.i.d. did not produce a greater fall in serum uric acid
      than losartan once a day. Losartan might be a useful therapeutic tool to control
      blood pressure and reduce serum uric acid levels in hypertensive patients with
      hyperuricaemia and gout.

PMID- 11593108
TI  - Changes of retinal neurons and glial fibrillary acid protein immunoreactive
      astrocytes in spontaneously hypertensive rats.
AB  - OBJECTIVE: The influence of arterial hypertension on retinal neurons and glial
      fibrillary acid protein (GFAP) immunoreactive astrocytes was investigated in
      spontaneously hypertensive rats (SHRs). METHODS: The retinas of 4- and 6-month
      old SHRs and age-matched Wistar-Kyoto rats (WKY) were investigated. A group of
      SHRs, treated from 4 to 6 months with the hypotensive drug hydralazine, was also
      examined. Microanatomical and immunohistochemical techniques associated with
      image analysis and the terminal deoxyribonucleotidyl transferase (TdT)-mediated
      biotin-16-dUTP nick-end labelling (TUNEL) technique for apoptosis or necrosis
      were used, as well as astrocyte molecular biology (Western blot) techniques.
      RESULTS: In 4-month-old SHR and WKY rats, retinal morphology and the number of
      retinal neurons and of GFAP-immunoreactive astrocytes were similar, with the
      exception of the occurrence of 1% of TUNEL-positive ganglionic neurons in SHRs.
      In 6-month-old SHRs a decrease of retinal volume and of the number of ganglionic
      neurons and photoreceptors was observed, compared with age-matched normotensive
      WKY rats or younger SHR and WKY rats. Two per cent of ganglionic neurons and 5%
      of photoreceptors were also TUNEL positive. In 6-month-old SHRs, hypertrophic
      perivascular GFAP-immunoreactive astrocytes were found, whereas their number was
      unchanged compared to younger cohorts or WKY rats. An increased expression of
      GFAP was also noticeable in SHRs by Western blot analysis. Hypotensive treatment
      with hydralazine partly countered retinal changes occurring in SHRs. CONCLUSIONS:
      The occurrence of neuronal and astroglial changes when a stable hypertension was
      developed, and their sensitivity to antihypertensive treatment, suggest that they
      may represent a hypertension-related phenomenon.

PMID- 11593109
TI  - A random comparison of fosinopril and nifedipine GITS in patients with primary
      renal disease.
AB  - OBJECTIVE: To investigate in a random comparison the capacity of an angiotensin
      converting enzyme inhibitor (fosinopril), and that of a long-acting
      dihydropiridine (nifedipine GITS) to modify the decay in renal function in
      patients with primary renal disease, exhibiting a progressive increase in serum
      creatinine during the previous 2 years. METHODS: A randomized, open-label,
      multicenter study with a minimum follow-up of 3 years. A total of 241 patients
      were included in the study. All of them were hypertensive and had a 25% or at
      least 0.5 mg/dl increase in the value of serum creatinine during the 24 months
      prior to entering the study. Initial doses of fosinopril and nifedipine GITS were
      10 and 30 mg respectively, and titration to 30 and 60 mg was performed if needed
      to obtain the expected blood pressure goal (< 140/90 mmHg). Furosemide, atenolol,
      and doxazosin were added as second, third, and fourth drugs if necessary, for
      blood pressure control. The primary end-point of the study was the appearance of
      double the serum creatinine values and/or the need to enter a dialysis programme.
      Secondary end-points were cardiovascular events, death, changes in 24 h
      proteinuria, and the evolution of serum creatinine. Data reflect the analysis
      performed by intention to treat. RESULTS: Mean age of the group was 54 +/- 14,
      and 59% were males. Primary glomerulonephritis (31%), nephrosclerosis (26%) and
      polycystic kidney disease (19%) were the three most frequent diagnostic findings.
      After 3 years of follow-up, 21% (27/127) of patients treated with fosinopril, and
      36% (40/112) of those receiving nifedipine GITS presented a primary end-point,
      (OR 0.47, 95% confidence intervals 0.26-0.84, P = 0.01). Renal survival was
      significantly better when fosinopril constituted the first step therapy (P =
      0.002). These results did not seem to be influenced by the type of primary renal
      disease. Proteinuria decreased at the end of the study by a mean of 57% in the
      fosinopril group and increased by 7% in the group receiving dihydropiridine.
      Blood pressure control did not differ among groups for diastolic values. During
      follow-up, however, the patients receiving ACEi showed systolic blood pressure
      values 4-6 mmHg lower. CONCLUSION: In patients with chronic renal failure and
      hypertension due to primary renal disease, fosinopril significantly differed from
      nifedipine GITS by its capacity to slow the progressive decay in renal function.
      The drugs also differed by their capacity to lower blood pressure. The better
      control, in particular of systolic blood pressure, in the fosinopril arm could
      have contributed in a relevant manner to the attainment of a better outcome when
      the ACEi was employed.

PMID- 11593110
TI  - Renal protective effects of chronic exercise and antihypertensive therapy in
      hypertensive rats with chronic renal failure.
AB  - OBJECTIVES: Patients with chronic renal failure are restricted to mild physical
      activity and tend to a lack of exercise. However, there have been few reports
      regarding the influence of chronic exercise on the progression of renal disease.
      Similarly, there are few animal models concerned with the effect of exercise
      training on improving renal function. Therefore, we assessed the renal effects of
      moderate chronic treadmill exercise in a remnant kidney model of spontaneously
      hypertensive rats (SHR) with chronic renal failure. We also assessed the effects
      of exercise and antihypertensive therapy on renal function. DESIGN AND METHODS:
      Eight-week-old SHR were subjected to 5/6 nephrectomy by removal of the left
      kidney and excision of two-thirds of the right kidney. The rats were divided into
      four groups: (i) no exercise (Non-EX); (ii) moderate exercise with treadmill
      running (20 m/min, 0 grade incline for 60 min) (EX); (iii) EX with an angiotensin
      converting enzyme (ACE) inhibitor, enalapril (2 mg/kg per day, i.p.); and (iv) EX
      with an angiotensin receptor antagonist, losartan (5 mg/kg per day, i.p.), for 4
      weeks. RESULTS: Chronic EX significantly attenuated the increase in proteinuria
      (P < 0.01) and significantly protected against increases in the index of
      glomerular sclerosis (IGS). Both enalapril and losartan with EX significantly
      decreased blood pressure (P < 0.001), and further decreased the IGS. In the
      stepwise multiple regression analysis, only antihypertensive drug remained in the
      model as a significant predictor of IGS (P < 0.0001). In contrast, exercise,
      antihypertensive drug and mean systolic blood pressure (weeks 1-4) remained in
      the model as a significant predictors of mean proteinuria (weeks 1-4) (all P <
      0.0001). CONCLUSIONS: These results suggest that exercise does not worsen renal
      function and has renal-protective effects in this model of rats. Moreover, the
      antihypertensive therapy has additional renal-protective effects in this model of
      rats.

PMID- 11593111
TI  - Relation of QT interval and QT dispersion to echocardiographic left ventricular
      hypertrophy and geometric pattern in hypertensive patients. The LIFE study. The
      Losartan Intervention For Endpoint Reduction.
AB  - OBJECTIVE: In hypertensive patients, left ventricular hypertrophy (LVH) predicts
      increased mortality, in part due to an increased incidence of sudden death.
      Repolarization-related arrhythmogenesis may be an important mechanism of sudden
      death in hypertensive patients with LVH. Increased QT interval and QT dispersion
      are electrocardiographic (ECG) measures of ventricular repolarization, and also
      risk markers for ventricular tachyarrhythmias. We assessed the relation of QT
      intervals and QT dispersion to echocardiographically determined left ventricular
      (LV) mass and geometry in a large population of hypertensive patients with ECG
      evidence of LVH. METHODS: QT intervals and QT dispersion were determined from
      baseline 12-lead ECGs in 577 (57% male; mean age 65 +/- 7 years) participants in
      the LIFE study. LV mass index (LVMI) and geometric pattern were determined by
      echocardiography and QT interval duration and QT dispersion were assessed in
      relation to gender-specific LVMI quartiles. RESULTS: In both genders, increasing
      LVMI was associated with longer rate-adjusted QT intervals. QT dispersion
      measures showed a weaker association with LVMI quartiles. Both concentric and
      eccentric LVH were associated with increased QT interval duration and QT
      dispersion. These relations remained significant after controlling for relevant
      clinical variables. CONCLUSIONS: In hypertensive patients with ECG evidence of
      LVH, increased LVMI and LVH are associated with a prolonged QT interval and
      increased QT dispersion. These findings suggest that an increased vulnerability
      to repolarization-related ventricular arrhythmias might in part explain the
      increased risk of sudden death in hypertensive patients with increased LV mass.

PMID- 11593112
TI  - Relation of hemodynamics and risk factors to ventricular-vascular interactions in
      the elderly: the Cardiovascular Health Study.
AB  - OBJECTIVE: To investigate the interaction between left ventricular (LV) geometry,
      carotid structure and arterial compliance in relation to hemodynamic stimuli and
      risk factors (plasma cholesterol, body mass index, insulin resistance, smoking
      habit, age, sex and race). DESIGN: Cross-sectional. METHODS: Echocardiography and
      carotid ultrasound were performed in 2375 elderly subjects without signs or
      history of prevalent cardiovascular disease, diabetes or renal disease (795 men;
      298 non-whites; 1215 hypertensive), from the cohort of the Cardiovascular Health
      Study. Arterial compliance was estimated by the prognostically validated ratio of
      stroke volume to pulse pressure (SV/PP) as the percent deviation (Delta%) from
      the value predicted by individual age, heart rate and body weight. RESULTS:
      Intima-medial thickness (IMT) was higher in the presence of LV hypertrophy (LVH)
      in normotensive and hypertensive subjects and was greatest in the presence of
      concentric LVH. Maximum carotid lumen diameter (CLD) was also higher in the
      presence of LVH (and was greatest with eccentric LVH, in association with
      relatively high values for stroke volume). After adjusting for blood pressure,
      maximum carotid lumen diameter was directly correlated with stroke volume, and
      IMT to LV mass (all P < 0.001). Similarly, IMT was also related to maximum
      carotid lumen diameter, independently of prevalent risk factors (P < 0.001).
      SV/PP-Delta% was reduced in both groups with concentric LV remodeling (both P <
      0.0001) or concentric LVH (both P < 0.05). Adjusting for risk factors did not
      affect these associations in normotensives, but made them insignificant in
      hypertensives. In normotensives, IMT was inversely related to SV/PP-Delta% (P <
      0.001), independently of risk factors, whereas no significant relation was found
      in hypertensives. CONCLUSIONS: The magnitudes of carotid intima-medial thickness
      and lumen diameter parallel levels of LV mass and geometry, and are directly
      related to stroke volume and arterial stiffness; this interaction is most evident
      in the presence of normal blood pressure, whereas it is affected by other
      cardiovascular risk factors when arterial hypertension is present.

PMID- 11593113
TI  - Ventricular production of natriuretic peptides and ventricular structural
      remodeling in hypertensive heart failure.
AB  - OBJECTIVES: Brain natriuretic peptide (BNP) is a strong predictor of left
      ventricular (LV) hypertrophy (LVH) and dysfunction. However, our recent studies
      suggested that LVH is not necessarily associated with enhanced production of BNP
      in hypertension. This study aimed to clarify the relation of the characteristics
      of hypertrophy with the degree of gene expression of BNP in the developmental
      process of hypertensive heart failure. METHODS: Serial changes in LV geometry,
      histology and atrial natriuretic peptide (ANP) and BNP mRNA levels, were assessed
      in a hypertensive heart failure model using Dahl salt-sensitive rats (n = 24). We
      further studied effects of alpha1-receptor antagonist (doxazosin: 1 mg/kg per
      day, n = 5) and angiotensin II type 1 receptor (AT1R) antagonist (candesartan
      cilexetil: 1 mg/kg per day, n = 5). RESULTS: The BNP mRNA level was not elevated
      at the compensatory hypertrophic stage when ANP mRNA level was elevated. BNP mRNA
      level was increased with further progression of hypertrophy and development of
      fibrosis. AT1R blockade prevented such fibrosis and further progression of
      hypertrophy with normalization of BNP mRNA levels. Compensatory hypertrophy was
      not suppressed; therefore, ANP mRNA level, although decreased, was still beyond
      the normal level. The alpha1-receptor blockade slightly attenuated LV hypertrophy
      with a slight decrease in ANP mRNA levels. LV fibrosis was not prevented, and the
      BNP mRNA level was not decreased. CONCLUSIONS: BNP gene expression is not
      enhanced by initial compensatory hypertrophy, but is enhanced by LV fibrosis and
      late stage progression of hypertrophy dependent on AT1R-mediated signaling
      pathway.

PMID- 11593114
TI  - Relation between clinical and therapeutic variables and quality of life in
      hypertension.
AB  - OBJECTIVE: Study the relation between quality of life (QoL) and various clinical,
      therapeutic and sociodemographic variables in treated hypertensive patients.
      MATERIAL AND METHODS: A prospective study was carried out in 92 primary care
      centres in Spain. A total of 269 hypertensive patients were selected and 106
      healthy normotensive individuals were included as controls. At the time of
      inclusion a wide range of clinical variables was documented. QoL was assessed at
      baseline and 1 month after the intensification of antihypertensive therapy, using
      a self-administered, specific hypertension, 56-item questionnaire in addition to
      the generic EuroQoL-5D. RESULTS: QoL was poorer among the hypertensive subjects
      than among the normotensive individuals, even adjusting for the differences
      observed between the groups (age, sex, education and working status). The same
      was found with the EuroQol-5D. In the hypertensive subjects, after applying a
      multiple regression equation, only four variables significantly retained their
      negative impact on QoL: sex (female), greater organ damage and higher heart rate
      and weight. After the intensification of antihypertensive therapy with
      irbesartan, QoL improved significantly. Neither the presence of side-effects
      during the month of follow-up, nor the degree of BP reduction showed a
      significant impact on QoL, although the latter came close to statistical
      significance. CONCLUSIONS: Hypertensive patients have significantly poorer QoL
      than normotensive subjects, even with adjustment for differences. In
      hypertensives, QoL is affected by some clinical variables that might help us to
      identify those with worse QoL. Intensification of antihypertensive therapy
      produced a positive impact on QoL.

PMID- 11593115
TI  - Fetal nutrition: how we become what we are.

PMID- 11593116
TI  - Large-volume paracentesis in the management of ascites in children.
AB  - BACKGROUND: Large-volume paracentesis has been evaluated for both therapeutic and
      diagnostic purposes in the management of ascites in cirrhotic adults. There are
      no published data relating to the safety, efficacy, or methods of this procedure
      in children. The objective of this study was to characterize the authors' initial
      experience with large-volume paracentesis (> 50 ml/kg of ascites) for removal of
      tense abdominal ascites in the pediatric population. METHODS: Retrospective chart
      review was performed of 21 large-volume paracentesis sessions in seven children
      (ages 6 months-18 years) with tense ascites that did not respond to other
      measures. RESULTS: Mean volume removed was 3,129 +/- 2,966 ml (mean +/- standard
      deviation) or 118 +/- 56 ml/kg over 2.9 +/- 3.7 hours by a 16-gauge intravascular
      catheter in 6 sessions, by an 18-gauge intravascular catheter in three sessions,
      and by a 15-gauge fenestrated, stainless-steel paracentesis needle in 12
      sessions. Large-volume paracenteses performed with the paracentesis needle had
      significantly shorter duration of drainage and faster flow rates than those
      performed with the intravascular catheter. The only complication encountered was
      decreased urine output in one session. CONCLUSIONS: Large-volume paracentesis is
      a safe and effective therapeutic method for managing tense abdominal ascites in
      children. The use of the paracentesis needle significantly improved the speed and
      efficiency of large-volume paracentesis compared with the intravascular catheter.

PMID- 11593117
TI  - Screening for celiac disease in children with recurrent abdominal pain.
AB  - BACKGROUND: The clinical presentation of celiac disease--a life-long gluten
      intolerance--may be characterized by chronic abdominal pain. The objective of
      this study was to determine if children with recurrent abdominal pain had a
      higher prevalence of antiendomysial antibodies (a serologic marker of celiac
      disease) compared with healthy children. METHODS: Children with recurrent
      abdominal pain and healthy control participants were recruited from the offices
      of community pediatricians. Serum samples were drawn and antiendomysial
      antibodies were measured in both groups. Demographic data included age, gender,
      height, and weight. RESULTS: A total of 200 children were recruited, of whom 173
      (87%) had serum samples drawn. Of these, 92 were children with recurrent
      abdominal pain and 81 were control participants. Only 2 of the 173 samples (1.2%)
      were positive for antiendomysial antibody. The frequency of antiendomysial
      antibody positivity in children with recurrent abdominal pain was 1 in 92 (1%;
      95% confidence interval, 0-6%) compared with 1 in 81 (1%; 95% confidence
      interval, 0-7%) in control participants. CONCLUSIONS: This community-based case
      control study found no association between recurrent abdominal pain and the
      prevalence of antiendomysial antibody. Therefore, these data do not support
      screening for celiac disease in the child with classic recurrent abdominal pain
      in the primary care setting.

PMID- 11593118
TI  - Intake and blood levels of fatty acids in treated patients with phenylketonuria.
AB  - BACKGROUND: Investigators in Italy and Spain have suggested that therapy for
      patients with phenylketonuria (PKU) may result in essential fatty acid (EFA)
      deficiency. Objectives of this study were to determine if the diets of patients
      with PKU in the United States provided adequate EFA intakes and whether patients
      could form long-chain polyunsaturated fatty acids. METHODS: Patients (1-13 years
      of age) with classic PKU undergoing therapy and their non-PKU sibling closest in
      age were compared. Nutrient intakes were calculated from 3-day diet diaries.
      Fatty acids in plasma and erythrocytes were identified and quantified. Paired t
      tests compared results for the patients and their non-PKU siblings. RESULTS:
      Twenty-eight patients and 26 siblings were studied. Mean fat intake was greatest
      by siblings (34.8 +/- 1.3% of energy) and lowest by Phenyl-Free-fed patients
      (19.5 +/- 1.2% of energy; P < 0.05). Fat intake (30.4 +/- 1.8% of energy) by
      Phenex-fed patients did not differ from that of siblings. Percentage of energy
      ingested as C18:2n-6 and C18:3n-3 did not differ significantly between patients
      and siblings. No clinically significant, consistent differences were found in
      fatty acid levels (wt%) in plasma or erythrocytes between patients with PKU and
      siblings. CONCLUSIONS: No patient in this study exhibited a Holman index of EFA
      deficiency. Siblings ingested animal protein containing C20:5n-3 and C22:6n-3
      fatty acids, and this may account for their greater wt% of these plasma and
      erythrocyte fatty acids. Because patients with PKU do not ingest fatty acids >C18
      but C20:4n-6, C20:5n-3, and C22:6n-3 were found in their plasma and erythrocytes,
      in vivo synthesis from C18:2n-6 and C18:3n-3 appears to occur. Lack of EFA
      deficiency in patients in this study may be the result of the use of canola and
      soy oils containing C18:2n-6 and C18:3n-3 rather than olive oil in the diets.

PMID- 11593119
TI  - Effects of therapy with lansoprazole on intestinal permeability and inflammation
      in young cystic fibrosis patients.
AB  - BACKGROUND: Defective pancreatic bicarbonate secretion with low intestinal pH or
      intestinal inflammation of any origin increase intestinal permeability in cystic
      fibrosis (CF). METHODS: In this open study, the authors evaluated the effect of a
      proton-pump inhibitor on intestinal permeability and inflammation in 14 young,
      pancreatic-insufficient CF patients. Permeability was measured by a three-sugar
      permeability test before and after 1 year of lansoprazole use, and urinary nitric
      oxide (NO) oxidation products were assessed before and during that year as a
      marker of inflammation. RESULTS: After 1 year of lansoprazole use, median urinary
      recovery percentages changed from 2.5% to 1.7% (P = 0.064), from 24.9% to 24.5%
      (no significance), and from 10.5% to 11.1% (no significance) for lactulose,
      mannitol, and L-rhamnose, respectively. Despite the fact that the median urinary
      excretion ratios decreased from 0.108 to 0.083 (P = 0.03) and from 0.246 to 0.176
      (P = 0.016) for lactulose and mannitol and for lactulose and rhamnose,
      respectively, they both remained increased. Median urinary NO products-to
      creatinine ratios were 0.287 for CF patients before lansoprazole and 0.130 for
      healthy control participants (P = 0.002). Although there was a tendency toward a
      decrease in the NO products-to-creatinine ratio during treatment, this was not
      significant at the end point. CONCLUSIONS: Intestinal permeability is
      considerably increased in CF patients and is partly corrected after the use of a
      proton-pump inhibitor for 1 year, which may point to a harmful effect of the acid
      luminal contents on the tight junctional related paracellular permeability
      pathway. The start and end values for the NO products-to-creatinine ratio in CF
      patients were not significantly different, but were considerably increased when
      compared with control participants (P = 0.002).

PMID- 11593120
TI  - Contamination of gastrostomy feeding systems in children in a home-based enteral
      nutrition program.
AB  - BACKGROUND: There are few data concerning the risk of contamination of enteral
      feeding systems via gastrostomy in children, and none for conditions that pertain
      to home-based care. METHODS: To investigate the risk of contamination of enteral
      feeding systems during the home-based care of 20 children receiving gastrostomy
      tube feeding, five samples were taken for analysis: two samples before the
      enteral feeding period (gastrostomy, enteral feeding system) and three after this
      period (gastrostomy, distal giving set, liquid remained in container).
      Microorganisms were identified and counted. Different factors were studied to
      elucidate their role in bacterial colonization: acid suppressive therapy,
      gastrostomy tube or button, hanging feeding time, rate of enteral feeding,
      gastric pullulation and retrograde contamination, manipulation error, and use of
      open or closed enteral feeding systems. RESULTS: Overgrowth was defined as a
      microorganismal load exceeding 10(4) colony-forming units (cfu)/mL. Overgrowth
      was present in 85% of gastrostomy samples before enteral nutrition started. Most
      microorganisms belonged to gastric flora. Some bacteria had an environmental
      origin or derived from cutaneous flora. Forty-five percent of the lines showed
      overgrowth at the end of enteral nutrition period, mainly with the same
      microorganism found in the gastrostomy. Closed enteral bags remained sterile,
      even if manipulation error occurred. Duration, rate of enteral feeding, and acid
      suppression treatment were not risk factors for overgrowth. CONCLUSIONS:
      Retrograde contamination of gastrostomy feeding systems occurs frequently. The
      preferential use of closed enteral feeding systems is recommended for home-based
      enteral nutrition programs.

PMID- 11593121
TI  - Hepatobiliary and pancreatic complications of ascariasis in children: a study of
      seven cases.
AB  - OBJECTIVES: This study presents seven cases of severe hepatobiliary and
      pancreatic complications of ascariasis in children. The authors describe the
      clinical, laboratory, and imaging findings, as well as the patients' clinical
      evolution. METHODS: These cases were studied within a period of approximately 1
      year and included children younger than 11 years (mean age, 4.4 years). The
      authors reviewed their medical history and evaluated the results of their main
      diagnostic examinations. RESULTS: All of the patients had vomiting, abdominal
      pain, pallor, and abdominal distension at presentation. Passage of Ascaris
      lumbricoides in stool occurred in five cases, emesis with worms in three, fever
      in three, and hepatomegaly in two. Five patients had pancreatitis, of which two
      were necrohemorrhagic and one had pseudocyst of the pancreas. In three patients,
      A. lumbricoides was present in the pancreatic duct. Two patients had hepatic
      abscess (28.6%), and one of them also had cholangitis. One of the patients with
      pancreatitis also had signs of cholecystitis at presentation. CONCLUSIONS:
      Ultrasonography was the imaging diagnostic method of choice and demonstrated the
      presence of A. lumbricoides in the biliary and the pancreatic ducts, as well as
      signs of pancreatitis, cholecystitis, and hepatic abscess. Endoscopic retrograde
      cholangiopancreatography, used to confirm the diagnosis, was a fundamental
      procedure in the treatment, allowing the removal of worms from the biliary duct
      in four of seven patients.

PMID- 11593122
TI  - Serologic markers of untreated celiac disease in Libyan children: antigliadin,
      antitransglutaminase, antiendomysial, and anticalreticulin antibodies.
AB  - BACKGROUND: There are, as yet, no data available about the incidence of celiac
      disease in Libya. The aim of this study was to test the occurrence of serologic
      markers in a group of Libyan children with positive clinical and histologic
      findings indicative of celiac disease diagnosis. METHODS: Thirty-nine children
      with untreated celiac disease and 50 healthy school children, all younger than 14
      years, were included in the study. Enzyme-linked immunosorbent assay for
      immunoglobulin G and immunoglobulin A (IgA) antigliadin, antitissue
      transglutaminase, and anticalreticulin antibodies was used to evaluate the
      serologic markers of the celiac patients. Immunoglobulin A antiendomysial
      antibodies were detected by indirect immunofluorescence using human umbilical
      cord tissue. RESULTS: Clinical symptoms at presentation were weight loss (82%),
      abdominal distension (61.5%), diarrhea or steatorrhea (59%), pallor (41%),
      abdominal pain (20.5%), constipation (15%), vomiting (10%), and short stature
      (7.7%). Most of these symptoms disappeared after introduction of a gluten-free
      diet. Of 39 patients, only 23 (59%) were endomysium positive and positive also in
      all other serologic markers. The second group of patients with positive clinical
      and biopsy findings but antiendomysial antibody-negative findings was subdivided
      into two subgroups according to the IgA antigliadin antibody results. Individuals
      in the IgA gliadin-negative subgroup also lacked IgA autoantibodies. CONCLUSIONS:
      The authors' findings stress the importance of serologic testing not only for
      screening but also for confirmation of celiac disease.

PMID- 11593123
TI  - Intestinal motility in an in vivo rat model of intestinal ischemia-reperfusion
      with special reference to the effects of nitric oxide on the motility changes.
AB  - BACKGROUND: To clarify the relation between intestinal ischemia-reperfusion (IR)
      and dysmotility, the authors investigated changes in the motility pattern in the
      duodenum and jejunum in an in vivo rat model of IR when artery- (and vein-) fed
      jejunum was clamped transiently. The authors also studied the effect of nitric
      oxide on the motility changes in this model by means of the administration of L
      NAME (N(G)-nitro-L-arginine methyl ester) or S-methylisothiourea sulfate (SMT).
      MATERIALS AND METHODS: A force transducer was sutured onto the serosal side of
      the duodenum or jejunum. After a 3-to 4-day recovery period, contractions were
      recorded during periods of preischemia, ischemia (60 minutes), and reperfusion
      (90 minutes). An intestinal IR was produced by clamping and releasing the
      mesenteric artery and vein with artery forceps. RESULTS: In the jejunum, there
      was a prolongation in the duration of contraction and there were decreases in the
      number of contractions (NC) during the IR. When treated with L-NAME, no decrease
      in the NC was observed during the 45 to 90 minutes after reperfusion. S
      methylisothiourea sulfate did not affect the IR-induced motility changes
      significantly. In the duodenum, there was a prolongation in the duration of
      contraction and a decrease in the NC and AC only during the reperfusion. L-NAME
      or S-methylisothiourea sulfate inhibited the decreases in the NC during the
      reperfusion. CONCLUSIONS: Intestinal IR causes motility changes in the ischemic
      site during the IR and in the nonischemic site during the reperfusion. The IR
      induced motility changes partly depend on nitric oxide production.

PMID- 11593124
TI  - Gastric electrical activity and gastric emptying in preterm newborns fed standard
      and hydrolysate formulas.
AB  - BACKGROUND: Because infant formulas containing hydrolyzed cow milk protein are
      used to reduce feeding intolerance and to improve gastric emptying, the effect on
      gastrointestinal motility of a hydrolysate formula was compared with that of a
      standard preterm formula. METHODS: Thirty-six preterm newborns with a gestational
      age of 32.2 +/- 2.3 weeks were assigned randomly to standard formula or
      hydrolyzed formula. Cutaneous electrogastrography and ultrasound examination of
      gastric emptying were performed simultaneously to evaluate gastrointestinal
      motility before and after the test meal. All recording sessions were performed 1
      week after infants had reached full enteral feeding. RESULTS: No significant
      difference in gastrointestinal symptoms was noted in the newborns fed the
      different formulas. In particular, regurgitation and vomiting were observed in
      78% versus 64% of preterm newborns after standard and hydrolyzed formula,
      respectively (Fisher exact test, not significant). No differences were found in
      terms of gastric electrical activity and gastric emptying time between the two
      groups. CONCLUSIONS: It seems unnecessary to use hydrolysate formulas to improve
      motility in preterm infants.

PMID- 11593125
TI  - Pediatric "PSC-IBD": a descriptive report of associated inflammatory bowel
      disease among pediatric patients with psc.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) in adults with primary sclerosing
      cholangitis (PSC) is characterized by pancolonic involvement, a high frequency of
      rectal sparing, and an increased risk of pouchitis and colorectal neoplasia. The
      clinical features of IBD in pediatric patients with PSC have not been well
      described. The aim of this study was to characterize the frequency, clinical
      features, and natural history of IBD in pediatric patients diagnosed with PSC.
      METHODS: A retrospective chart review was performed for all patients 18 years of
      age or younger diagnosed with PSC seen at the Mayo Clinic between 1975 and 1999.
      Endoscopic and histologic features and surgical and postsurgical outcomes were
      recorded. RESULTS: Fifty-two children with PSC were identified. Forty-three
      patients (84%) were also diagnosed with IBD. In 36 of 43 cases, there was a
      sufficient diagnostic evaluation to allow a detailed review. Thirty-two of 36
      patients (89%) had ulcerative colitis and 4 of 36 patients (11%) had Crohn's
      disease. In 4 of 36 patients (11%), IBD was asymptomatic. Although the most
      frequent endoscopic presentation of IBD was universal colitis, endoscopic rectal
      sparing was frequently noted (27% of colonoscopic studies). Of the four patients
      diagnosed with Crohn disease, in none did perianal, fistulizing, or stricturing
      disease develop. Proctocolectomy was performed in six patients (17%); three
      operations were performed for dysplasia. Pouchitis complicated four of the five
      ileal pouch-anal anastomoses procedures. CONCLUSIONS: Among pediatric patients
      (1) PSC without IBD is uncommon; (2) asymptomatic IBD may be associated with PSC;
      (3) because the time to dysplasia may be accelerated, once the diagnosis of IBD
      is made in the setting of PSC, heightened endoscopic surveillance may be
      indicated; (4) pouchitis occurs frequently in these patients.

PMID- 11593126
TI  - Clinical relevance of precore and basal core promoter variants of hepatitis B
      virus during natural hepatitis B e antigen seroconversion may be overstated.
AB  - BACKGROUND: Clinical relevance of nucleotide changes in precore and basal core
      promoters in the hepatitis B virus genome during hepatitis B e antigen
      seroconversion may be overstated. The authors investigated the existence and
      changes in the relative proportion of variants to wild virus that occur with
      seroconversion. METHODS: Sera from 30 school-aged long-term hepatitis B virus
      carriers, including 11 tested before and after seroconversion during 1 to 8 years
      of follow-up, were evaluated for variations in nucleotide sequences of the basal
      core promoter (T1762 and A1764), precore region (A1869), and carboxyl-terminus of
      the X region of the hepatitis B virus genome using an amplification refractory
      mutation detection system with mutant-specific primers. RESULTS: All variants
      were found to already exist before seroconversion at various wild-type/mutant
      ratios. The positive rates of these variants were not changed with loss of
      hepatitis B e antigen. Although there was a relative increase in the
      concentration of these mutants in wild-type/mutant mixed populations, most
      patients with only a wild-type population maintained the same pattern after loss
      of hepatitis B e antigen. CONCLUSIONS: Our results indicate that hepatitis B
      virus exists as a quasi species, and correlations of nucleotide sequences with
      clinical and serologic findings must be done with caution.

PMID- 11593127
TI  - Effect of feeding yogurt versus milk in children with acute diarrhea and
      carbohydrate malabsorption.
AB  - BACKGROUND: The aim of this study was to compare the effect of infant formula and
      the same formula subjected to microbial fermentation (yogurt) on the duration of
      diarrhea in young children with acute watery diarrhea, with or without reducing
      substances in stools. METHODS: One hundred twelve well-nourished children, aged 3
      to 24 months, who were admitted to the hospital with acute watery diarrhea were
      included in a randomized trial. After appropriate rehydration, they were fed
      either an infant formula (group M, n = 56) or the same formula fermented with
      Lactobacillus bulgaricus and Streptococcus thermophilus (group Y, n = 56). The
      two feedings were comparable in lactose concentration (40 to 42 g/L), pH 4.5,
      flavor, and texture. The groups were subdivided into those with or without
      reducing sugars in stools at presentation. The presence of reducing sugars in
      stool was used as a marker of carbohydrate malabsorption. RESULTS: Group M and
      group Y had comparable clinical characteristics at admission, including the
      number of patients with reducing sugars in stools (n = 31 in group M and 27 in
      group Y). The success rate (cessation of diarrhea and appropriate weight gain 7
      days after enrollment into the study) was similar in both groups (82% in group M
      vs. 84% group Y). Clinical failure was 3.6% in both groups. The percentage of
      patients withdrawn from the study for medical reasons (5.4% in group M vs. 7.1%
      in group Y) or withdrawn at the parents' request (8.9% in group M vs. 5.4% in
      group Y) was similar. Duration of diarrhea and number of stools were
      significantly less in group Y compared with group M. Forty-eight hours after
      inclusion, diarrhea was still present in 62% of group M versus in 35% of group Y
      (P < 0.002). In children with reducing sugars in stools, the rate of success
      (82%) was similar in groups M and Y, but the duration of diarrhea and number of
      stools per day were significantly decreased in group Y. Forty-height hours after
      inclusion, diarrhea was still present in 75% of group M patients and in 20% of
      group Y patients who had reducing substances in the stool. CONCLUSION: Young
      children with acute watery diarrhea, without malnutrition or associated disease,
      can be equally well treated with feeding of either infant formula or yogurt.
      Yogurt feeding is associated with a clinically relevant decrease in stool
      frequency and duration of diarrhea in children who have reducing sugars in
      stools.

PMID- 11593128
TI  - Experience with an anesthesiologist interventional model for endoscopy in a
      pediatric hospital.
AB  - BACKGROUND: Endoscopy is now a routine part of the work-up for many patients with
      gastrointestinal symptoms. Adults tolerate these procedures well, with either no
      sedation or a relatively light level. In contrast, children often require deep
      sedation or a general anesthetic to successfully perform these procedures.
      Therefore, pediatric endoscopies may require more time, personnel, and monitoring
      equipment to provide optimal conditions for the patient. The goals of this
      retrospective case series were to describe the anesthesia times and recovery
      duration of the different procedures, the types and amounts of medications
      commonly used, and the types and rates of complications experienced. METHODS:
      Patients (2,306) who underwent endoscopy in the Arkansas Children's Hospital
      endoscopy suite during a 4-year period were identified. A random sample of 720
      charts was reviewed retrospectively. RESULTS: Patients ranged in age from younger
      than 1 year to 29 years. Patients most often had abdominal pain or multiple
      gastrointestinal symptoms. Sixty-eight percent of patients underwent
      esophagogastroduodenoscopies; 30% colonoscopy or a combination of the two. Ninety
      five percent of patients received a propofol-based anesthetic. Midazolam,
      fentanyl, and alfentanil were frequently used as supplemental agents.
      Complications occurred infrequently and were airway related. All complications
      were easily treated, with no adverse sequelae. CONCLUSIONS: This model of
      anesthesiologist-provided sedation/anesthesia for gastrointestinal endoscopy
      procedures has been extremely successful in the Arkansas Children's Hospital and
      has served to heighten awareness of many issues surrounding sedation and
      anesthesia outside of the operating room, while ensuring a high level of care is
      provided.

PMID- 11593129
TI  - Height and weight fail to detect early signs of malnutrition in children with
      cystic fibrosis.
AB  - BACKGROUND: Many children with cystic fibrosis grow poorly and are malnourished.
      This study was undertaken to determine whether extensive anthropometry could
      detect early signs of malnutrition in prepubertal children with cystic fibrosis
      to prevent deficits in height and weight. METHODS: Height, weight, six skin folds
      (triceps, subscapular, supraspinale, abdominal, front thigh, and medial calf) and
      five girths (arm relaxed, forearm, chest, thigh, and calf) were measured in a
      cross-sectional study of children aged 6 to 11 years with cystic fibrosis.
      RESULTS: The children with cystic fibrosis were shorter and lighter for their age
      and gender than those in the reference groups. The mean weight and height z
      scores for the girls with cystic fibrosis were lower than those for the boys,
      significantly so for z weight ( P < 0.05). Although, the mean percent ideal body
      weight value of 98.6% suggested that the children with cystic fibrosis were
      adequately nourished, most of the measures of muscularity and adiposity of the
      children with cystic fibrosis were significantly lower than those of the
      reference group ( P < 0.05). The z scores of the anthropometric measures revealed
      that the deficit in muscularity of the children with cystic fibrosis was
      relatively much greater than the deficit in adiposity. CONCLUSIONS: The percent
      ideal body weight index does not seem to be an adequate measure of nutritional
      status in children with cystic fibrosis. Anthropometric assessments should
      include skin-fold and circumference measurements of numerous sites on the upper
      and lower body, the trunk, and the limbs to detect deterioration in nutritional
      status early. Early detection of deficits in nutritional status may result in the
      adverse effects of malnutrition on height and weight, and possibly clinical
      status, being prevented.

PMID- 11593130
TI  - The buried bumper syndrome complicating percutaneous endoscopic gastrostomy in
      children.

PMID- 11593131
TI  - Atypical celiac disease presenting as obesity-related liver dysfunction.

PMID- 11593132
TI  - A case of glycogen storage disease IA with multiple hepatic tumors managed by
      transcatheter arterial embolization and an acarbose diet.

PMID- 11593133
TI  - Headache during mesalamine therapy: a case report of mesalamine-induced
      pseudotumor cerebri.

PMID- 11593134
TI  - A rare cause of hepatomegaly: 3-hydroxy-3-methylglutaryl coenzyme-a lyase
      deficiency.

PMID- 11593136
TI  - Disappearance of macroamylasemia in a celiac patient after treatment with a
      gluten-free diet.

PMID- 11593135
TI  - Are children with cystic fibrosis who are treated with a proton-pump inhibitor at
      risk for vitamin B(12) deficiency?
AB  - BACKGROUND: In a recent study, the authors demonstrated the beneficial effect of
      proton-pump inhibitors (PPI) on fat malabsorption and bone mineral content in
      children with cystic fibrosis (CF). Prolonged use of PPI could result in vitamin
      B(12) deficiency as a consequence of impaired release of vitamin B(12) from food
      in a nonacid environment. The aim of this study was to evaluate the vitamin B 12
      status of CF patients either treated with a PPI or not by measuring vitamin B(12)
      and homocysteine blood levels, the latter being a sensitive indicator of vitamin
      B(12) deficiency. METHODS: The study population consisted of 20 CF patients, 11
      patients treated with a PPI for at least 2 years and 9 patients not treated with
      a PPI, and 10 healthy, age-matched control participants. Homocysteine blood
      levels were measured by high-performance liquid chromatography, and vitamin B(12)
      levels were measured by a competitive protein-binding assay. RESULTS: Vitamin
      B(12) levels were significantly higher in both CF groups compared with the
      control participants (PPI+, P = 0.02; PPI-, P = 0.009). There was no significant
      difference in vitamin B(12) levels between both CF groups. Homocysteine levels
      were normal and similar in all groups. CONCLUSIONS: Cystic fibrosis patients
      treated with a PPI for at least 2 years show no signs of vitamin B(12)
      deficiency.

PMID- 11593137
TI  - Antibodies to human tissue transglutaminase for the diagnosis of celiac disease.

PMID- 11593138
TI  - Nutritional knowledge of obese and nonobese children.

PMID- 11593139
TI  - Other experience with H. pylori therapy.

PMID- 11593140
TI  - Celiac disease and HLA-DQ2 association in patients with Turner syndrome.

PMID- 11593141
TI  - [Collagenous colitis. A study of 11 cases].
AB  - BACKGROUND: Collagenous colitis (CC) is a rare large bowel inflammatory disorder.
      The aim of this retrospective study was to analyze extra-digestive manifestations
      of CC, associated systemic diseases, clinical course and response to therapeutic
      regimens. PATIENTS AND METHODS: Between 1989 and 1999, eleven patients were
      diagnosed as having CC, in two Departments of Internal Medicine and
      Gastroenterology, on the basis of usual criteria: chronic watery diarrhea,
      endoscopic examination showing normal findings and subepithelial collagen band
      thicker than 10 micrometer. RESULTS: Ten women and one man, age 39 to 88 years
      (mean: 66.6), had had their diarrhea for 1 to 240 months before diagnosis (mean:
      48). Associated extra-digestive manifestations were: weight loss (3 cases out of
      11), inflammatory arthralgia (4 cases), fever (2 cases), pelvispondylitis (2
      cases), autoimmune thyroiditis (2 cases), and Sharp syndrome (1 cases).
      Laboratory abnormalities were: inflammatory syndrome (3 cases), anemia (5 cases),
      hypogammaglobulinemia (3 cases), and hypoalbuminemia (4 cases). Stool cultures
      and parasite examination were negative in all patients. Therapy used successively
      for CC until resolution of chronic diarrhea (uncontrolled with symptomatic
      treatment) was: sulfasalazine in 7 patients (beneficial (B) in 5 out of 7), 5
      aminosalicylic acid in 6 (B: 2/6), corticosteroids in 2 (B: 2/2), azathioprine in
      1 (B: 1/1). After a mean follow-up of 18 months (range: 1-72), resolution of CC
      was observed in 8 out of 11 patients. DISCUSSION: Mean characteristics of CC
      were: female predominance (91%), presence of extra-digestive manifestations
      (36%); mucosal inflammation with subepithelial collagen band and frequent
      association to rheumatic or autoimmune diseases suggest an immune basis for CC.
      Usefulness of systematic colon biopsies is underlined. Clinical course is often
      favorable with sulfasalazine and 5-aminosalicylate acid. Corticosteroids are
      rarely used.

PMID- 11593142
TI  - [Diabetic foot ulcers: anti-infectious strategies].
AB  - Infection is a common problem in diabetic patients with foot ulcers. The
      diagnosis of infection is not always easy to establish, but must be made for
      proper therapeutic decision making. In addition to local care, search for
      arteriopathy and strict control of blood glucose, treatment of infected foot
      ulcers requires an appropriate anti-infectious strategy. We developed diagnostic
      and therapeutic decisional algorithms from data available in the literature in
      order to establish a management strategy for different clinical situations. The
      fundamental role of clinical assessment is underlined and the different causal
      microorganisms are recalled, together with the anti-microbial activity and bone
      concentrations of the main antibiotics used. An optimal anti-infection work-up
      can undoubtedly significantly reduce the number of amputations in diabetic
      patients.

PMID- 11593143
TI  - [Hereditary non polyposis colorectal cancer].
AB  - Hereditary non polyposis colorectal cancer (HNPCC) is characterized by an excess
      of early colorectal carcinomas, preferentially located on the ascending colon,
      associated with a variety of extracolonic cancers. The recent demonstration of
      germline mutations in DNA mismatch repair genes in HNPCC patients enhanced the
      interest due to the syndrome. Molecular genetic testing of HNPCC has become
      available, and should help physicians to recommend specific modalities for the
      surveillance and the management of patients with such a high cancer risk.

PMID- 11593144
TI  - [Role of the pathologist in management of familial cancers].
AB  - Pathologists have long been in charge of the morphological analysis of human
      cancers, and have been used to be at the end of a chain in the diagnostic
      procedure. With the search for somatic mutations and new prognostic markers, the
      pathologists have become key-members in oncogenetics. New modalities for tissue
      fixation, microdissection of tumors, and forwarding of specimens to the molecular
      biologists are therefore requested. Two examples are presented to illustrate the
      need for tumor DNA, with the diagnostic utility of a microsatellite testing as a
      prescreening test in HNPCC tumors, and the search for new prognostic markers in
      some inherited predispositions to breast cancers.

PMID- 11593145
TI  - [Molecular diagnostic techniques in oncogenetics].
AB  - A few definitions Exploration methods (unknown mutations) Diagnostic methods
      (known mutations) New technologies and perspectives What should be done when no
      mutation can be identified? Research strategies in oncogenitics

PMID- 11593146
TI  - [Ethical issues in oncogenetics].
AB  - Thanks to progress in molecular genetics, we now have new powerful tools allowing
      certain or highly presumptive prediction of disease course. The impact on medical
      practice has been disconcerting. These tools may be very helpful for many
      patients and families concerned by genetic diseases. For health professionals,
      the new knowledge must be handled with care to discern the true patient benefit.
      The patient-doctor relationship - from information delivery, with its known or
      unknown effects on the individual patient and his/her family and offspring, to
      the new prospects for gene therapy - must be conducted in a spirit of free
      exchange allowing responsible real life decision making. Living necessarily
      implies taking risks, but also trusting human capacity to establish mutual
      relationships on the basis of trust, fellowship and fraternity.

PMID- 11593147
TI  - [Colon cancer and nutritional genetics: modifier genes].
AB  - About 5% of colon cancer cases correspond to classic hereditary monogenic
      mendelian transmission involving at least 8 major genes of predisposition to this
      tumor. Genes with more moderate effects, in association with other genes can
      contribute to the occurrence of sporadic polygenic forms. These genes confer
      susceptibility to environmental factors and can play the role of aggravating or
      protective modifier genes in the different hereditary forms. Foods can interact
      with these genes and modulate their expression. Moreover sequence variations
      (polymorphisms) in these genes may also be responsible for slower or more rapid
      metabolism of nutrients leading to toxic or carcinogenic compounds. If some
      foods, or "pharmafoods" can have beneficial effects in some individuals with a
      particular subtype of the disease, others can be inefficient or even detrimental
      in patients with the same disease but with a different genetic origin or if the
      genetic background is different. Moreover tumorigenic processes are diverse.
      Tumor progression depends on genetic and environmental factors different from
      tumor initiation and on the site of the tumor along the colon tract. Interactions
      with the gut flora, the lymphoid system and specific features of growth of the
      colon mucosa are also important parameters. Today with a formidable genetic
      knowledge arising from the genome project, new epidemiological data integrating
      the genetic data for multiple markers and a better knowledge of the tumorigenic
      processes involved, a new discipline is emerging. "Nutrigenetics" which is the
      study of hereditary basis of individual variations in response to foods opens for
      the oncoming decade the era of a personalised predictive medecine based on a
      nutrition adapted to the genetic make up of each of us.

PMID- 11593148
TI  - [Acute hepatitis and drug dermatitis due to fenofibrate (Secalip)].

PMID- 11593149
TI  - [Anaphylactic shock induced by celecoxib].

PMID- 11593151
TI  - [Update on legionellosis].

PMID- 11593152
TI  - [Bronchopulmonary disease in drug abusers].
AB  - Drug abuse is a growing problem in industrialized countries, opening the way to
      new diseases of the respiratory tract. It has been demonstrated that regular
      inhalation of cannabis has the same consequences as tobacco smoking. The same
      cannot be said for other drugs. Cocaine, amphetamines or crack expose the patient
      to particular toxic effects: in addition to barotrauma related to the
      administration route, syndromes of acute respiratory distress have been
      described. These result either from bronchial reactions, asthma exacerbation or
      eosinophil bronchopneumonia, or alveolar involvement: intra-alveolar bleeding,
      pulmonary edema or organized pneumonia. Respiratory complications induced by
      opiates, often used in injections, are related to central alveolar
      hypoventilation and/or the development of injury from pulmonary edema or
      pneumonia. The pathophysiology of these lesions is not perfectly understood.
      Besides these specific conditions, infection is a major problem in drug abusers,
      irrespective of the drug: bacterial pneumonia, tuberculosis, HIV infection are
      much more frequent in this high-risk group. Finally repeated intravenous
      injections of various drugs designed for oral intake can lead to severe
      complications such as pulmonary hypertension or toxic interstitial lung disease.
      Summarizing, respiratory diseases in drug abuses can take on a wide range of
      quite complex presentations. Occasional or regular use of illicit drugs can lead,
      not exceptionally, to severe respiratory complications requiring rapid
      management. Knowledge of the principal complications and the appropriate
      diagnostic procedures is indispensable.

PMID- 11593153
TI  - [Neoadjuvant chemoradiotherapy and peroperative radiotherapy for non-small-cell
      lung cancer of the apex. A study of 5 cases].
AB  - The management of superior sulcus tumors with Pancoast 's syndrome is not well
      defined, especially in view of their low frequency. Even if surgery performed by
      "en bloc" resection of the tumor and the chest wall is recommended, neoadjuvant
      treatment could have a potential benefit on the resecability and pain control. We
      report five cases of Pancoast tumors (NSCLC), treated by radiotherapy and
      chemotherapy before surgery. Four tumors was on stage IIIb. A regimen with
      radiotherapy (50 Gy) and chemotherapy (cisplatinum + etoposide) was initially
      performed. Four tumors were resected, with 2 complete pathologic responses and
      good control on pain. Three patients received radiotherapy during surgery. No
      toxic reaction was observed. This regimen may be discussed with locally advanced
      tumors and poor prognosis.

PMID- 11593154
TI  - [Psychological profile of patients with COPD: contribution of Semiometry].
AB  - Patients with chronic bronchitis often ignore, or pretend to ignore, their
      disease and generally consult very late. The physician's advice is often quite
      vague and centered on smoking. One of the objectives of this study was to better
      understand the psychological profile of patients with chronic bronchitis in order
      to better apprehend the patient-physician relationship and therapeutic options.
      Semiometry was designed to overcome the problem encountered by physicians who
      would like to understand who their patients are without directly asking them. The
      concept is based on submitting very ordinary words to these subjects and asking
      them whether they like the word or not. An analysis of their responses allows a
      very deep understanding of their psychological profile. Briefly, the patient
      physician relationship is quite difficult in COPD. The patient "brings" the
      disease to the physician, "putting" it in his hands and asking him to cure it
      without having to do anything concerning himself, his life or his behavior. The
      physician is called on to answer this challenge that can be expressed as "trying
      to get the patient to play the game without getting caught".

PMID- 11593155
TI  - [Active tracheo-bronchial caseous tuberculosis. Ten patients].
AB  - BACKGROUND: We report 10 cases of active endobronchial tuberculosis in female
      patients. PATIENTS AND METHODS: Diagnosis of endobronchial tuberculosis was
      established by demonstrating the presence of Koch bacilli in the bronchial
      washings or at pathology examination of a bronchial mucosa biopsy. Follow-up was
      available for 5 of the 10 cases. RESULTS: These women were aged 19 to 756 years.
      Clinical signs included persistent cough (n=10), wheezing (n=10), dyspnea (n=5),
      dysphonia (n=4) and fever (n=8). Chest x-ray was normal in 4 cases but showed
      condensation in 4 others with infiltration of the superior lobe in 2 cases.
      Bronchoscopy findings were characteristic with a thick layer of white caseum on
      the mucosa. Koch bacilli were found in all bronchial wash specimens. Pathology
      examination confirmed the diagnosis of tuberculosis in 5 of the 10 cases.

PMID- 11593156
TI  - [Fatal toxic respiratory epitheliolysis. Subacute tracheo-bronchial desquamation
      in Stevens-Johnson syndrome].
AB  - Acute bronchial mucosal sloughing related to Toxic Epidermal Necrolysis (Lyell
      syndrome) is widely reported in literature. On the contrary severe respiratory
      involvement is rare in post-infectious or toxic Epitheliolysis (Stevens-Johnson
      syndrome). There is no well-known predictive sign of bronchial epithelium
      involvement. An 18-year-old patient was admitted for Stevens-Johnson syndrome
      related to sulfasalazine (salazosulfapyridine). There were no respiratory signs.
      An acute respiratory failure occurred 36 hours after from admission due to an
      obstructive and desquamative necrosis of the tracheobronchial epithelium. We
      purpose that a fiberoptic laryngoscopy should be performed even in non-dyspneic
      patients suffering from Stevens-Johnson syndrome if hypersecretion is present.
      Fiberoptic bronchoscopy can be helpful in these cases.

PMID- 11593157
TI  - [Beginning rheumatoid arthritis revealed during bronchiectasis surinfections.
      Value of cyclic antibiotherapy?].
AB  - Incidence of symptomatic bronchiectasis (BR) occurs in around 2% in patients with
      late rheumatoid arthritis (RA). Its seems that the association BR-RA could be a
      worsening factor for outcome of RA patients. A 58-year-old woman without dry
      syndrome, suffering from bronchial purulence over one year was admitted to the
      Department of Pneumology for hemoptysis and arthritis (knees, ankles, and
      wrists). Three prior episodes of inflammatory articular pain had occurred after
      transient bronchial purulence or pneumonitis. CT-scan showed bilateral
      bronchiectasis. Diagnosis of early RA was proved after the third episode of
      bronchial purulence related to a strain of Haemophilus influenzae. A strain of
      Coxiella burnetii was probably responsible for one of the three bronchial
      surinfections. Latex and Waaler Rose tests were transiently positive during the
      first episode, and became positive after the third one. At that time, RA was
      relevant in view of ARA criteria. Cyclic prophylactic antibiotic regimens could
      be proposed to patients suffering from RA-BR association, in contrast to the
      cases of patients with isolated BR. This approach could prevent destabilization
      of RA and reinforce of anti-rheumatic therapy. Activation and release of
      cytokines (NFk-B, TNF-alpha), and/or bacterial epitopes seems to be directly
      responsible for the articular destabilization.

PMID- 11593158
TI  - [Localized tracheobronchial amyloidosis: a rare cause of pseudo-asthma].
AB  - Localized tracheobronchial amyloidosis is an uncommon disease of unknown cause.
      Bronchial amyloid deposits can occur as focal nodules or multifocal infiltration
      of the submucosa. Clinical signs are not specific and the chest x-ray is usually
      normal. Diagnosis is rarely evoked before bronchial biopsies are done. We report
      a case of tracheobronchial amyloidosis disclosed by asthmatiform dyspnea. The
      diagnosis was obtained at bronchial fibroscopy performed as part of the work-up
      for secondary pneumonia.

PMID- 11593159
TI  - [Bilateral alveolar opacity].

PMID- 11593160
TI  - Conflict of interest in peer-reviewed journals.

PMID- 11593161
TI  - Exploring health-related quality of life in patients with diseases of the ear,
      nose, and throat: a multicenter observational study.
AB  - OBJECTIVES: This study was undertaken to explore which diseases of the ear, nose,
      and throat impact daily functioning of patients in an outpatient setting and to
      observe how specific demographic variables affect health-related quality of life
      (HRQOL) in these patients. METHODS: This multicenter observational study was
      conducted anonymously during a 6-week period at outpatient clinics in adults > or
      = 18 years of age. The Short Form-12 (SF-12) was used to assess HRQOL.
      Demographic and clinical variables were recorded for each patient. RESULTS: In
      data from 5806 patients, the SF-12 physical component score was 43.8, and the
      mental component score was 49.4. SF-12 physical and emotional functioning scores
      for ENT patients were poorer than established standards (50 +/- 10) for the U.S.
      population (P < 0.001). CONCLUSIONS: ENT diseases adversely affect the HRQOL in
      patients visiting their otolaryngologist. Clinical and demographic variables are
      important considerations in the measurement of HRQOL.

PMID- 11593162
TI  - Bariatric surgery for treatment of sleep apnea syndrome in 15 morbidly obese
      patients: long-term results.
AB  - OBJECTIVE: To evaluate the long-term outcomes of bariatric surgery with respect
      to respiratory disturbance index (RDI) in sleep apnea syndrome (SAS). DESIGN:
      Case series with long-term follow-up (1 to 12 years). SETTING: Private clinic in
      an academic tertiary referral center. PATIENTS: Fifteen morbidly obese patients
      (10 men, 5 women) who were referred for the treatment of severe SAS.
      INTERVENTION: For all 15 patients who presented with severe SAS, nasal positive
      airway pressure breathing was either not available or was not tolerated by the
      patient; therefore, bariatric surgery was performed as a means of treatment for
      SAS. MAIN OUTCOME MEASURES: RDIs and minimum oxygen saturation were measured both
      preoperatively and postoperatively (1 to 12 years after surgery). RESULTS: Weight
      loss ranged from 60 to 220 pounds (27 to 100 kg). RDI decreased by at least 55%
      in each patient, and all patients with tracheostomies (8 of 15) had their
      tracheostomy tubes removed. Average RDI preoperatively was 96.9 and average RDI
      postoperatively was 11.3. Results were similar for all 15 patients in that
      minimum oxygen saturation increased during sleep from an average preoperative
      minimum oxygen saturation of 58.7% to an average postoperative minimum oxygen
      saturation of 85.2%. CONCLUSIONS: Bariatric surgery as a means of treating SAS in
      the morbidly obese provides effective long-term reduction in RDI. Bariatric
      surgery also significantly improves minimum oxygen saturation in morbidly obese
      patients with SAS. Biliopancreatic bypass is more effective in reducing RDI to
      normal values than vertical banded gastroplasty.

PMID- 11593163
TI  - A multi-institutional study of radiofrequency volumetric tissue reduction for
      OSAS.
AB  - OBJECTIVES: Radiofrequency volume reduction (RFTVR) is a minor procedure directed
      at reducing the tongue base volume to treat obstructive sleep apnea. Subjective
      and objective treatment effectiveness was evaluated. STUDY DESIGN AND SETTING:
      Two separate prospective, matched, nonrandomized, open enrollment treatment
      groups (RFTVR, n = 73 and nasal continuous positive airway pressure (CPAP, n =
      99) were concurrently enrolled in a multicenter study. RESULTS: Fifty-six (76.7%)
      RFTVR completed PSG with a mean 5.4 +/- 1.8 treatments (13,394 +/- 5459 joules).
      Perioperatively, acute pain was mild to moderate; edema, mucosal erosion,
      paresthesia, tinnitus were infrequent; and speech, swallowing taste, or throat
      irritation were unchanged. Self-reported outcomes did not differ between RFTVR
      and CPAP groups. Mean apnea/hypopnea index decreased (40.5 +/- 21.5 to 32.8 +/-
      22.6 events/hr, P < 0.01). Electrolyte solution injected predicted results (r =
      0.43, P < 0.001). The most severe complication was abscess (1.1%). CONCLUSION:
      RFTVR improves apnea/hypopnea index. Improvement may be related to solution
      injected with treatment. RFTVR and CPAP clinical outcomes improvement were
      similar. CLINICAL SIGNIFICANCE: In mild obstructive sleep apnea, treatment of
      symptomatic outcomes with RFTVR may be an alternative to CPAP.

PMID- 11593164
TI  - Temperature-controlled radiofrequency tissue volume reduction in the human soft
      palate.
AB  - OBJECTIVE: To validate the use of temperature-controlled radiofrequency energy
      applied to the soft palate in a multicenter setting for reduction of snoring in a
      minimally morbid manner. METHODS: Prospective, nonrandomized multicenter study of
      113 patients who had a respiratory disturbance index less than 15 and minimum
      oxygen saturation not less than 85% and who were seeking treatment for habitual
      disruptive snoring. Patients were given either single or multiple lesions to the
      soft palate during each treatment session. RESULTS: Patients received 1978 J on
      average with an overall average of 2.4 treatments. Snoring scores went from an
      average of 7.8 (visual analog scale (VAS), 0-10) pretreatment to 3.2
      posttreatment. Pain was minimal, averaging 1.7 (VAS 0-10) on days 1 to 6.
      Complications were few and transient, and mild. CONCLUSIONS: The multiple lesion
      protocol was the most successful; reducing snoring from 7.6 to 2.7, on a VAS with
      an average of 1232 J delivered over 1.6 treatments. Temperature-controlled
      radiofrequency was found to be a minimally invasive, well-tolerated procedure
      that was safe and efficacious in this study group.

PMID- 11593165
TI  - Incidence of pulmonary edema after tracheotomy for obstructive sleep apnea.
AB  - OBJECTIVE: The phenomenon of postobstructive pulmonary edema (POPE) has been
      associated with the relief of upper airway obstruction, which itself is
      fundamental to the pathophysiology of obstructive sleep apnea (OSA). A review of
      patients with OSA undergoing tracheotomy was performed to characterize this
      process. STUDY DESIGN: Retrospective chart review of study patients with OSA
      undergoing tracheotomy and of control patients without OSA undergoing tracheotomy
      for unrelated problems. Chest radiographs were reviewed in a double-blind fashion
      to score posttracheotomy changes in pulmonary status. SETTING: Academic tertiary
      referral center. RESULTS: Thirty (67%) of 45 OSA patients treated by tracheotomy
      had evidence of POPE, whereas only 5 (20%) of 25 control group patients had
      increased pulmonary edema. The remaining 15 (33%) of 45 OSA patients and 20 (80%)
      of 25 control patients had either no change or an improved pulmonary status.
      Those with OSA that developed POPE were mostly graded as having mild pulmonary
      edema (22/30, 73%). Far fewer were graded as having moderate pulmonary edema
      (6/30, 20%), and fewer still with severe pulmonary edema (2/30, 7%). Two (7%) of
      45 patients with severe POPE died of complications related to cor pulmonale in
      the postoperative period. CONCLUSION: Results support maintaining a high index of
      suspicion for the development of postobstructive pulmonary edema in patients
      treated for OSA. Treatment options, such as positive pressure ventilation and
      diuresis, and an increased awareness of this condition may help reduce the
      morbidity and mortality associated with treatment of this disease.

PMID- 11593166
TI  - Pharyngoesophageal pressure monitoring in sleep apnea syndrome.
AB  - OBJECTIVES: This study tests the sensitivity and the specificity of overnight
      pharyngoesophageal pressure measurement for identification and classification of
      obstructive sleep apnea (OSA). METHODS: Fifty-nine snoring patients undergoing
      polysomnography were invited to have simultaneous pharyngoesophageal manometry.
      We used a soft silicone catheter with 4 microtip pressure sensors at different
      levels. RESULTS: The apnea hypopnea indexes (AHIs) measured by the 2 methods were
      highly correlated (r = 0.971). Manometry was 100% sensitive and specific in
      excluding OSA and identifying severe OSA. It was 90% sensitive in identifying
      moderate OSA and 80% sensitive in identifying mild OSA. CONCLUSION: Overnight
      ambulatory pharyngoesophageal manometry is a reliable tool for the exclusion of
      OSA and identification of severe OSA. It has additional advantages of localizing
      the level of obstruction and identifying the upper airway resistance syndrome and
      can be performed at home. It is cost-effective when compared with polysomnography
      and may aid in treatment selection for individual patients.

PMID- 11593167
TI  - Intrinsic nasal muscles and their electromyographic evaluation after external
      septorhinoplasty.
AB  - OBJECTIVES: Rhinoplastic surgery is performed for the improvement in the
      appearance of the nose, but it should not cause any detrimental effect on the
      intrinsic muscles. This study was conducted to evaluate the influence of the
      external rhinoplasty on intrinsic nasal muscles. METHODS: Twenty-one patients
      were operated on by external septorhinoplasty. Functions of the nasal muscles
      were assessed by electromyography in response to voluntary nasal movements in
      patients before and after surgery. RESULTS: Postoperative electromyographic
      activities of the muscles were significantly less than preoperative measurements
      for all movements. CONCLUSION: Influence of the surgical incisions, alterations
      of the sites of origin and/or insertion of the muscles, and the postoperative
      healing process can be incriminated for the decreased muscular activity. Nasal
      muscle function requires a better appreciation and respect for the achievement of
      the best aesthetic and functional results. The nasal valve reconstructive
      procedures should be applied routinely to compensate for this inevitable muscular
      involvement.

PMID- 11593168
TI  - Late-phase allergy and eustachian tube dysfunction.
AB  - OBJECTIVE: This study investigated the role of late-phase allergy in the
      development of otitis media with effusion. METHODS: Brown Norway rats were
      sensitized to ovalbumin and later challenged transtympanically. Eustachian tube
      ventilatory function was assessed 2, 4, 8, 24, 28, and 32 hours postchallenge by
      measuring passive opening and closing pressures, active clearance of positive and
      negative middle ear pressure, and mucociliary clearance. RESULTS: The results
      demonstrate that exposure to transtympanic allergen induces eustachian tube
      dysfunction and subsequent formation of effusion. Allergic animals showed
      significant increases in passive and active opening pressures, as well as a
      decreased ability to actively clear middle ear pressure. Finally, the mucociliary
      was significantly impaired in all sensitized rats exposed to transtympanic
      allergen. CONCLUSION: These findings demonstrate that late-phase allergy leads to
      significant eustachian tube dysfunction and subsequent formation of effusion by
      impairing the ventilatory and clearance functions of the eustachian tube.

PMID- 11593169
TI  - Inhalant allergy and Meniere's disease: Use of electrocochleography and
      intranasal allergen challenge as investigational tools.
AB  - INTRODUCTION: In an earlier study, we demonstrated the feasibility of using
      electrocochleography (ECoG) to document changes in inner ear function objectively
      after intranasal challenge of patients with inhalant allergy (with no prior
      immunotherapy) and Meniere's disease, using the antigen to which they were most
      sensitive. OBJECTIVE: We expand on this earlier study and continue to investigate
      the feasibility of this model in a subset of patients with inhalant allergy and
      Meniere's disease after immunotherapy. STUDY DESIGN: Prospective study of 11
      patients identified with both Meniere's disease and inhalant allergy in the
      practices of 2 neurotologists at our institution. Patients underwent a baseline
      ECoG, followed by intranasal challenge with the allergen to which they were most
      sensitive. This was followed by a second ECoG. RESULTS: Six of 11 patients had at
      least 1 year of immunotherapy (group 1), and 5 of 11 had had 0 to 6 months of
      immunotherapy (group 2). Four of 6 group 1 patients had a >15% increase in SP/AP
      ratio after immunotherapy. In group 2, 2 patients increased the SP/AP in at least
      1 ear. No patient with a normal ECoG experienced vestibular symptoms after
      allergen challenge, whereas 2 of group 1 and 2 of group 2 had vestibular symptoms
      with abnormal ECoGs. CONCLUSION: This protocol is a useful tool for investigating
      the relationship of inhalant allergy and Meniere's disease, but needs a larger
      group of patients and further study to draw valid statistical conclusions.

PMID- 11593170
TI  - Experimental trauma to the malar eminence: fracture biomechanics and injury
      patterns.
AB  - OBJECTIVES: To document patterns of facial fractures after trauma to the malar
      eminence and to elucidate biomechanical factors relevant to the injury patterns.
      STUDY DESIGN AND SETTING: Studies were conducted on 14 cadaver heads. Study
      variables included impact velocity, contact area, impact force, and zygomatic
      skin thickness. Bony fractures and clinical injury patterns were documented. A
      fracture severity rating scale was devised and statistically correlated to the
      study variables using regression ANOVA analysis. RESULTS: A broad spectrum of
      facial fracture patterns was found. Skin thickness and surface area did not
      correlate with fracture severity (P = 0.67, P = 0.83, respectively). Impact force
      demonstrated a trend toward significance (P = 0.14). Velocity was most
      correlative with fracture severity (P = 0.07). A critical threshold velocity (3.5
      m/s) was found to correlate with the most severe fracture patterns. CONCLUSIONS:
      A broad spectrum of facial fracture patterns was demonstrated after experimental
      trauma to the malar eminence. Contact surface area and zygomatic skin thickness
      were not found to be significant factors in fracture severity. Velocity, rather
      than impact force, was most correlative with fracture severity. The most severe
      fracture patterns were elicited by velocities above 3.5 m/s.

PMID- 11593171
TI  - Diving after stapedectomy: clinical experience and recommendations.
AB  - OBJECTIVES: Much controversy exists concerning the risk of inner ear barotrauma
      after stapes surgery in scuba and sky divers. Uniform consensus has not been
      established regarding poststapedectomy barorestrictions. The purpose of this
      study was (1) to determine the prevalence of adverse auditory and/or vestibular
      sequelae in patients after stapedectomy related to scuba and sky diving, and (2)
      to offer recommendations on barometric exposure after stapes surgery. STUDY
      DESIGN: Survey questionnaires were mailed to 2222 patients who had undergone
      stapedectomies at a single tertiary otologic referral center between 1987 and
      1998. Two hundred eight of the initial 917 respondents (22.7%) had snorkeled,
      scuba, or sky dived after stapes surgery, and 140 of these responded to a second
      questionnaire detailing dive protocols, otologic symptoms, and their relationship
      to the diving activities. Of the 140, 28 had scuba or sky dived. Their survey
      data were analyzed and their medical records were reviewed. RESULTS: Four of the
      22 scuba divers (18.1%) experienced otologic symptoms at the time of diving.
      These included otalgia on descent (3/22; 13.6%), tinnitus (1/22; 4.5%), and
      transient vertigo on initial submersion (1/22; 4.5%). One patient had sudden
      sensorineural hearing loss and vertigo develop 3 months after scuba diving, which
      he related to noise exposure. He was subsequently found to have a perilymph
      fistula, which was successfully repaired. Of the 9 patients who sky dived, 2
      patients (22.2%) reported otologic symptoms during the dive. No significant
      diving-related long-term effects indicative of labyrinthine injury were seen in
      any of the 28 patients. CONCLUSIONS: Stapedectomy does not appear to increase the
      risk of inner ear barotrauma in scuba and sky divers. These activities may be
      pursued with relative safety after stapes surgery, provided adequate eustachian
      tube function has been established.

PMID- 11593172
TI  - Implications of sound levels generated by otologic devices.
AB  - OBJECTIVE: Exposure to loud noise can result in sensorineural hearing loss. In
      otology, a wide variety of devices are used that have significant noise output,
      both to the operator and the patient. This study quantifies and compares the
      sound pressure levels (SPL) of a variety of otologic instruments. METHODS: Using
      a calibrated sound pressure level meter, the peak and impulse sound pressure
      levels of several otologic instruments were determined at 1 cm from their
      application to human temporal bones. Devices measured were an air-powered drill
      with a cutting burr, an electric micro-drill, and KTP, CO(2), and erbium lasers.
      RESULTS: Impulse sound pressure levels for the KTP laser, CO(2) laser,
      microdrill, air-powered drill and erbium laser were 67, 71, 90, 105, and 105 dBA,
      respectively. Peak sound pressure levels were 81, 89, 102, 118, and 132 dBA,
      respectively. CONCLUSIONS: Use of the KTP laser, CO(2) laser, and microdrill
      result in impulse levels of less than 100 dBA. Although the impulse levels of the
      erbium laser and the air-powered drill were equivalent, the peak sound pressure
      levels of the erbium laser were significantly higher. These high sound pressure
      levels may increase the chance for hearing loss. Like any tool, lasers and drills
      have benefits and risks. The results of this study demonstrate significant
      differences in SPLs of common otologic lasers and drills. Although noise-induced
      hearing loss is a function of both SPL and duration of exposure, surgeons should
      consider these differences when selecting and applying these tools, especially
      when used on or adjacent to the ossicular chain and stapes footplate.

PMID- 11593173
TI  - Changes in external ear resonance after 3 types of surgery in the patients with
      chronic otitis media.
AB  - OBJECTIVE: This study was designed to identify the external ear resonance
      characteristics of patients with tympanic membrane perforation and to investigate
      subsequent changes in external ear resonance, depending on the length of the
      postoperative period and which of 3 different types of operation was performed:
      tympanoplasty with canal wall-up mastoidectomy, epitympanoplasty, and canal wall
      down mastoidectomy. STUDY DESIGN AND SETTING: A total of 227 ears of 188 patients
      and 96 control ears comprised the study. We measured the gain and frequency of
      the first peak of external ear resonance with a real ear analyzer. RESULTS: Gain
      and frequency of the first peak recorded in the preoperative group did not differ
      from those of the control group. However, negative peaks appeared around 1 to 1.5
      kHz in half of these ears. The gain increased markedly in all 3 postoperative
      groups. The canal wall-down mastoidectomy and epitympanoplasty groups showed
      significantly lower frequencies compared with the tympanoplasty with canal wall
      up mastoidectomy and control groups, but there was no difference between them.
      The increased gain diminished over time, but the peak gain did not equalize with
      that of the controls, even after 15 months. CONCLUSIONS: Additional gain should
      be considered of around 1 to 1.5 kHz for hearing aid users with tympanic membrane
      perforation. Postoperative changes in external ear resonance should be expected
      in patients with chronic otitis media, suggesting that fine readjustments of the
      hearing aid may be necessary.

PMID- 11593174
TI  - The external approach for submucosal lesions of the larynx.
AB  - OBJECTIVE: The surgical excision of benign submucosal lesions of the larynx can
      be performed using a variety of techniques including direct laryngoscopy and
      external approaches. We propose that small submucosal lesions of the larynx can
      be removed via the external approach without a tracheotomy. STUDY DESIGN:
      Retrospective chart review. SETTING: Six patients at The Long Island Jewish
      Medical Center and at the New York University School of Medicine underwent an
      external approach for the removal of benign submucosal laryngeal lesions without
      tracheotomies. Lesions included a mixed laryngopyocele, an internal
      laryngopyocele, a mixed laryngocele, a paraganglioma, a neurilemmoma and a
      lymphoma. Follow-up ranged from 1 to 9 years. RESULTS: All patients were female
      with an average age of 72. No patient required a tracheotomy. One patient
      remained intubated for 24 hours postoperatively to ensure an adequate airway.
      Mild dysphagia was noted in all patients, but it was short-lived and did not
      require alternate methods of alimentation. There have been no recurrences of
      disease. CONCLUSION: The external approach without tracheotomy allows for good
      exposure with minimal functional disability for the removal of benign submucosal
      lesions of the larynx.

PMID- 11593175
TI  - Proton pump inhibitor resistance in the treatment of laryngopharyngeal reflux.
AB  - OBJECTIVE: To describe the occurrence of relative proton pump inhibitor (PPI)
      drug resistance in the treatment of laryngopharyngeal reflux (LPR). STUDY DESIGN
      AND SETTING: A retrospective review was performed for 1053 consecutive adults
      undergoing double-probe (simultaneous esophageal and pharyngeal) pH testing in
      our laboratory. Two hundred five patients who had pH studies performed while
      taking at least a daily dose of PPI therapy were identified; 167 qualified for
      further analysis. The pH data was reviewed for the presence of abnormalities in
      either esophageal or pharyngeal acid exposure to evaluate drug efficacy. RESULTS:
      Forty-four percent (74/167) of the study patients demonstrated abnormal levels of
      acid exposure. Results were further analyzed to compare failure rates based on
      different dosage regimens. Patients on once daily doses of PPI failed at a rate
      of 56%, with lower failure rates for higher-dose regimens. CONCLUSIONS: A
      significant number of LPR patients on PPI therapy demonstrate relative drug
      resistance.

PMID- 11593176
TI  - Globe sparing orbital exenteration.
AB  - OBJECTIVE: Orbital exenteration has long been the oncologic standard for
      malignant craniofacial lesions that invade the periorbita/orbit from adjacent
      locations. Although oncologically sound, this radical surgical procedure is
      cosmetically disfiguring for all patients. Most of the reconstructive options
      available are complex, requiring further surgery and/or expense. We herein
      introduce an alternative surgical technique for radical orbital surgery that
      spares the globe, thereby allowing an early, aesthetic appearance at a nominal
      cost. STUDY DESIGN AND SETTING: Twenty consecutive patients requiring an
      oncologic orbital exenteration and meeting the indications for the new procedure
      underwent surgery at a tertiary care medical center. Follow-up ranged from 1 to 6
      years. RESULTS: Only 1 patient recurred in the orbit due to an error in patient
      selection. There was no surgical morbidity resulting from the globe-sparing
      technique itself. CONCLUSION: Globe-sparing orbital exenteration is a one-step,
      oncologically sound, aesthetically superior, low-cost alternative for those
      patients requiring radical orbital surgery and reconstruction.

PMID- 11593177
TI  - Laryngeal compartmentalization after radiation therapy in a canine model.
AB  - OBJECTIVE: We set out to study the effects of radiation therapy on laryngeal
      tissue barriers in a canine model as described by Welsh. STUDY DESIGN: India ink
      was injected into 1 vocal fold on irradiated and nonirradiated canine larynges.
      RESULTS: The india ink dye spread more prominently into the supraglottis of the
      irradiated specimens by submucosal lymphatics. Larger dye volumes simulating
      larger tumor bulk spread to the contralateral larynx in irradiated specimens.
      CONCLUSION: Conservation laryngeal surgery for laryngeal carcinoma is a popular
      method of treatment. Some surgeons advocate partial laryngectomy for radiation
      failures; in other instances, it is the primary modality of treatment. These
      findings suggest a cautious approach when planning conservative laryngeal surgery
      after radiation therapy failures of glottic carcinoma.

PMID- 11593178
TI  - Patterns of spread in recurrent head and neck squamous cell carcinoma.
AB  - OBJECTIVE: To examine the pattern of spread regarding recurrent disease in
      primary head and neck squamous cell carcinoma. STUDY DESIGN AND SETTING: A
      retrospective study reviewed 128 patients who underwent primary tumor resection
      and postoperative radiation and/or chemoradiation for squamous cell carcinoma at
      Loyola University Medical Center from July 1993 to August 1998. Patterns of
      spread of recurrent disease were grouped according to site of recurrence and
      compared with the histopathology. RESULTS: Of 128 patients, 40 (32%) had
      recurrent disease, 22 (17%) died without disease, and 66 (51%) are disease free.
      Although the recurrences in patients who were N0 were primarily local-regional
      (8/11), the majority of recurrences in patients that were N+ with extracapsular
      nodal spread involved distant sites (18/24); 17/18 involved metastasis to the
      lung. SIGNIFICANCE: This study gives the first report at our institution of
      patterns of spread in recurrent head and neck squamous cell cancer and compares
      these patterns within subgroups of patients based on the extent of neck disease
      at the time of primary surgical resection. CONCLUSION: Not only was there a
      higher rate of recurrent disease in patients with extracapsular nodal spread,
      there was a much higher involvement of distant metastatic sites as opposed to
      local-regional recurrence more often seen with the N0 neck. The most common site
      of distant metastasis was the lung.

PMID- 11593179
TI  - Laryngotracheal reconstruction in subglottic stenosis: an ancient problem still
      present.
AB  - BACKGROUND: Subglottic stenosis is an ancient but persistent problem as a cause
      of airway obstruction. The etiology and the results of surgical treatment with
      thyrotracheal anastomosis were reviewed. METHODS: Fifty-six patients with
      subglottic stenosis were studied. All were subjected to laryngotracheal
      reconstruction by thyrotracheal anastomosis with partial resection of the
      cricoid. RESULTS: Of all 56 cases of subglottic stenosis, 48 (86%) had history of
      previous tracheal intubation, and only 8 (14%) had different non-neoplastic
      obstructive processes such as scleroma, direct injury, hamartoma, and
      amyloidosis. Immediate results were good in all cases. After 1 year follow-up,
      results of thyrotracheal anastomosis were successful in 44 (91%). In 4 other
      cases a restenosis was observed. Eight patients were lost to follow-up.
      CONCLUSIONS: Subglottic stenosis is still frequent after tracheal intubation, but
      other causes must be considered. Laryngotracheal reconstruction with
      thyrotracheal anastomosis with partial cricoid resection was feasible with good
      results in 91% of the cases with follow-up, but this procedure must be performed
      by a skilled surgical team.

PMID- 11593180
TI  - Meniere's disease in military aircrew.

PMID- 11593181
TI  - Cochlear implant for deafness and blindness from meningitis.

PMID- 11593182
TI  - Chondroma of the bony external auditory canal.

PMID- 11593183
TI  - Vestibular stimulation after cochlear implantation in common cavity deformity.

PMID- 11593184
TI  - Temporal bone histopathology after treatment by a large amount of cisplatin: a
      case study.

PMID- 11593185
TI  - Atypical presentations of cat scratch disease in the head and neck.

PMID- 11593186
TI  - Complicated cirrhosis of the liver in patients with head and neck cancer.

PMID- 11593187
TI  - Synchronous contralateral oral and cervical ranula.

PMID- 11593188
TI  - Lingual granular cell tumor.

PMID- 11593189
TI  - Parapharyngeal foreign body.

PMID- 11593190
TI  - Thyroglossal duct cyst causing intralaryngeal obstruction.

PMID- 11593191
TI  - Malignant eccrine spiradenoma of the neck: a case report.

PMID- 11593192
TI  - Benign cystic teratoma of the parotid gland.

PMID- 11593193
TI  - Presentation of prostatic adenocarcinoma with cervical lymphadenopathy: two case
      reports and review of the literature.

PMID- 11593194
TI  - Lingual thyroid associated with chronic cough.

PMID- 11593195
TI  - Antimicrobial treatment guidelines for acute bacterial rhinosinusitis.

PMID- 11593197
TI  - Paroxetine in the treatment of tinnitus.

PMID- 11593199
TI  - Estimation of left ventricular end-diastolic pressure by color M-mode Doppler
      echocardiography and tissue Doppler imaging.
AB  - OBJECTIVES: The aim of this study was to estimate left ventricular end-diastolic
      pressure (LVEDP) noninvasively by tissue Doppler imaging and color M-mode
      echocardiography. MATERIAL AND METHODS: We studied 3 groups of patients who were
      proven by angiography to be free of significant coronary artery lesions (<40%
      stenosis) with an LVEDP < 10 mm Hg (group A: n = 24; 16 men, 18 women; mean age
      +/- SD = 55 +/- 13 years), an LVEDP of 10 to 15 mm Hg (group B: n = 21; 17 men, 4
      women; mean age 56 +/- 11 years), or an LVEDP > 15 mm Hg (group C: n = 35; 20
      men, 15 women; mean age 58 +/- 9 years). Tissue Doppler imaging of the lateral
      mitral annulus and color M-mode imaging of the mitral valve in the apical 4
      chamber view were obtained with an echocardiographic system. Early and late
      diastolic velocities (Em and Am, respectively), Em deceleration time (EmDT), Am
      time (Am-t), and mitral propagation velocity time delay (VpDT) were measured in
      each patient. RESULTS: In group A, sensitivity and specificity for EmDT < or =
      100 ms, Am-t < or = 90 ms, Em/Am > or = 1, and VpDT < or = 45 ms were found to be
      0.57 and 0.89, 0.66 and 0.88, 0.86 and 0.92, and 0.73 and 0.89, respectively. In
      group B, sensitivity and specificity for EmDT 100 to 120 ms, Am-t 90 to 110 ms,
      Em/Am 1 to 0.5, and VpDT 45 to 60 ms were found to be 0.57 and 0.84, 0.69 and
      0.82, 0.66 and 0.75, and 0.55 and 0.83, respectively. In group C, sensitivity and
      specificity for EmDT > 120 ms, Am-t > 110 ms, Em/Am < 0.5, and VpDT > 60 ms were
      found to be 0.88 and 0.81, 0.71 and 0.80, 0.86 and 0.72, and 0.78 and 0.86,
      respectively. CONCLUSION: The EmDT, Am-t, Em/Am, and VpDT measurements obtained
      noninvasively by left ventricular tissue Doppler imaging and mitral flow
      propagation velocity were found to be useful in the estimation of LVEDP.

PMID- 11593200
TI  - Age-dependent changes in regional diastolic function evaluated by color Doppler
      myocardial imaging: a comparison with pulsed Doppler indexes of global function.
AB  - The goals of this study were to evaluate possible normal age-related changes in
      regional myocardial relaxation as detected by color Doppler myocardial imaging
      (CDMI) velocities and to compare the extent of any such changes with age-induced
      changes in global diastolic function. In 80 healthy subjects (aged 21 to 72
      years, equally subdivided by decades) the mitral flow velocities in early
      diastole (E) and atrial contraction (A) were recorded as were the velocities of
      left ventricular (LV) motion of early (EDV) and late diastole (LDV) in the 16
      standard LV segments, and their ratios were calculated. In healthy persons
      younger than 40 years, all segments showed an EDV/LDV ratio > 1, whereas in
      healthy persons aged 40 years or older the mean EDV of all segments decreased,
      and the mean LDV increased, resulting in a significant decrease of the mean
      EDV/LDV ratio with age. Values of EDV/LDV ratios were higher than E/A ratios (P
      <.0001), but their changes with age correlated well with each other (r = 0.805).
      With increasing age, an EDV/LDV ratio <1 was observed more often in basal
      segments (P <.001, compared with mid and apical segments) and less often in
      segments of anteroseptal and posterior walls viewed from the parasternal window.
      The presence of >50% segments with an EDV/LDV ratio <1 was associated with an E/A
      ratio <1. Regional diastolic function indexes as evaluated by CDMI changed with
      increasing age in a heterogeneous way and influenced global diastolic function
      parameters.

PMID- 11593201
TI  - Association between myocardial right ventricular relaxation time and pulmonary
      arterial pressure in chronic obstructive lung disease: analysis by pulsed Doppler
      tissue imaging.
AB  - This study assessed right ventricular function in chronic obstructive lung
      disease and pulmonary hypertension by Doppler tissue imaging. Doppler
      echocardiography of the right ventricle and Doppler tissue imaging of the
      tricuspid annulus were performed in 63 subjects: 20 healthy controls, 20 with
      lung disease, and 23 with both lung disease and pulmonary hypertension. Two
      dimensional tricuspid systolic plane excursion was lower in patients with
      pulmonary hypertension than in the other 2 groups. Doppler tricuspid inflow
      measurements distinguished patients in both of the diseased groups from the
      control subjects, but they did not differentiate patients with pulmonary
      hypertension from those without it. The ratio of peak E-wave to peak A-wave
      velocities derived by Doppler tissue imaging was significantly lower and the
      myocardial acceleration time longer in both groups of lung disease than in the
      control group. Only myocardial relaxation time distinguished the 3 groups (all P
      <.01); a gradual increase in time occurred, with the shortest time seen in
      controls, a longer time in patients with chronic obstructive lung disease without
      pulmonary hypertension, and the longest time in patients with lung disease and
      pulmonary hypertension. In the overall population including subjects with at
      least minimal tricuspid regurgitation, myocardial relaxation time was positively
      related to pulmonary systolic pressure. In conclusion, Doppler tissue imaging
      distinguishes subsets of patients affected by lung disease with or without
      pulmonary hypertension and identifies patients with different levels of pulmonary
      artery systolic pressure.

PMID- 11593202
TI  - Analysis of systolic and diastolic time intervals during dobutamine-atropine
      stress echocardiography: diagnostic potential of the Doppler myocardial
      performance index.
AB  - Systolic and especially diastolic Doppler time intervals may be early markers of
      myocardial ischemia inducible by dobutamine-atropine stress echocardiography
      (DASE). We postulated that the Doppler myocardial performance index (MPI) may
      help differentiate ischemic from nonischemic responses. Hemodynamic and Doppler
      echocardiography variables were measured prospectively at every stress level of
      DASE in 32 patients (mean age 67 +/- 13 years). Adequate recordings were obtained
      in 27 patients; 13 had an ischemic response (group I) and 14 a nonischemic
      response (group II). Heart rate differed between groups at baseline. At
      equivalent peak stress, left ventricular wall motion score index was
      significantly greater and ejection fraction lower in group I patients. Of the
      Doppler variables, only the MPI consistently differed between groups,
      irrespective of the number of stress levels compared. The Doppler MPI may be a
      useful adjunct to wall motion analysis in the detection of myocardial ischemia
      during DASE.

PMID- 11593203
TI  - The importance of pulmonary venous flow measurement for evaluating left
      ventricular end-diastolic pressure in patients with coronary artery disease in
      the early stage of diastolic dysfunction.
AB  - Transmitral flow pattern assessed by pulsed Doppler echocardiography is widely
      used to evaluate left ventricular end-diastolic pressure (LVEDP). A restrictive
      mitral flow pattern is well recognized as a finding of severely elevated LVEDP.
      On the other hand, an abnormal relaxation pattern can be interpreted many ways.
      For example, some patients who display an abnormal relaxation pattern have a mild
      impairment of left ventricular (LV) relaxation as a result of aging, and others
      have severely impaired LV diastolic function. To evaluate LVEDP in patients with
      abnormal relaxation mitral filling patterns, we studied 55 patients who had
      coronary artery disease with abnormal relaxation pattern who underwent elective
      cardiac catheterization. We recorded the transmitral and pulmonary venous flow
      velocity curves and measured the duration of the mitral A wave (MAd) and
      pulmonary venous reversal wave during atrial contraction (PAd). Positive
      correlations were found between PAd and LVEDP (r = 0.65, P <.01) and between PAd
      MAd and LVEDP (r = 0.7, P <.0001); however, MAd was not significantly correlated
      with LVEDP. In conclusion, PAd must be measured for an accurate evaluation of LV
      end-diastolic pressure in patients with an abnormal relaxation pattern in the
      transmitral flow velocity curve.

PMID- 11593204
TI  - The validation of volumetric real-time 3-dimensional echocardiography for the
      determination of left ventricular function.
AB  - The objective of this study was to validate a real-time 3-dimensional
      echocardiography (3DE) technique for the determination of left ventricular (LV)
      volume and ejection fraction (EF). In 10 mongrel dogs, an electromagnetic flow
      (EMF) probe was placed on the aorta, and the thorax was closed. Transthoracic
      imaging was performed during multiple hemodynamic conditions (n = 58) with
      simultaneous measurement of stroke volume (SV) with the use of EMF. From the
      volumetric data set, LV volumes were manually traced off-line by 2 independent
      observers with an apical rotation method (6 planes) and a conventional method
      (biplane) in a subset of conditions. This tracing technique was also evaluated in
      18 human subjects in whom the calculated EF values were compared with values
      derived by multigated radionuclide angiography (MUGA). Excellent correlation and
      close limits of agreement were noted between SV measured by 3DE and EMF (r =
      0.93) in dogs. In comparison with EMF-derived SV, 3DE provided better correlation
      than the biplane method (r = 0.93 versus r = 0.61). Interobserver and
      intraobserver variabilities were comparable (r = 0.94 and r = 0.94,
      respectively). In a comparison of MUGA-derived EF values and those obtained by
      3DE in human subjects, 3DE provided better correlation than the biplane method (r
      = 0.94 versus r = 0.85). Real-time 3DE accurately measures left ventricular
      volumes transthoracically over a wide range of hemodynamic conditions in dogs and
      accurately determines EF in humans.

PMID- 11593205
TI  - Real-time 3-dimensional echocardiographic evaluation of left ventricular volume:
      correlation with magnetic resonance imaging--a validation study.
AB  - BACKGROUND: The purpose of our study was to validate the ability of real-time 3
      dimensional echocardiography (RT3D) to measure cardiac volume. METHODS: We
      studied 25 patients with various cardiac disorders who had a regular heart rhythm
      and a good precordial echocardiographic window. Each patient underwent complete
      transthoracic echocardiography (TTE), RT3D, and magnetic resonance imaging (MRI)
      studies. Left ventricular dimension was calculated from slices of the whole left
      ventricle obtained by 7 different equidistant azimuth tilts. Planimetry of the
      endocardial (for volume data) and epicardium (for mass data) surface was
      performed for each azimuth tilt. The left ventricular end-diastolic volume
      (LVEDV) and the left ventricular end-systolic volume (LVESV) were calculated. The
      cardiac mass data were derived with the formula (Epicardial volume - LVEDV) x
      1.055. The parameters of LVEDV, LVESV, stroke volume, ejection fraction, and
      cardiac mass were compared with those derived from MRI. RESULTS: No statistically
      significant differences were found between the data from RT3D and MRI (P > or
      =.05). Good correlations were found between these two methods for left ventricle
      volume and mass measurements (r from 0.92 to 0.99). However, a weaker correlation
      was found with larger chamber sizes because extrapolation was necessary for the
      volume of myocardial segments that were not covered by the small sector angle.
      CONCLUSIONS: For data acquisition, RT3D is faster than either TTE or MRI. It is
      also better than MRI for measuring cardiac volume and mass. To improve results
      with larger cardiac chamber sizes, enlargement of the sector angle will be
      necessary.

PMID- 11593206
TI  - Accuracy and reproducibility of coronary flow rate assessment by real-time
      contrast echocardiography: in vitro and in vivo studies.
AB  - Real-time myocardial contrast echo (MCE) provides the potential to assess
      myocardial blood flow from time-intensity refilling curves after high-energy
      bubble destruction. This study validated the accuracy of this approach and the
      effect of specific examination variables and instrument settings on results. The
      effects of examination depth and angle as well as dynamic range, pulse repetition
      frequency, and line density were assessed with the use of in vitro incremental
      flow rates produced in an in vitro tissue phantom. In vivo recordings of real
      time imaging with an infusion of a contrast agent (Optison) were obtained in 7
      open-chest dogs with graded left anterior descending artery stenosis at baseline
      and during adenosine hyperemia, and were compared with flow probe measurements.
      After bubble destruction, time-intensity data were fitted to an exponential
      function, and the rate of intensity increase (b) and peak plateau intensity (A)
      were derived from refilling curves. In vivo real-time values for b, but not A,
      correlated closely with flow probe measures (r = 0.93). A similar correlation for
      b was observed in vitro (r = 0.98). The correlation between flow rate and b was
      influenced by several examination variables, including depth, angle, and
      instrument settings. Real-time MCE provides accurate quantification of coronary
      flow by assessing the rate of microbubble refilling. However, this parameter may
      be affected by several examination and instrument variables. Therefore, real-time
      MCE refilling measures are best applied by comparing baseline values with those
      of stress studies.

PMID- 11593207
TI  - Compensatory responses of left atrial conduit flow to atrial fibrillation with
      acute myocardial infarction in a canine model.
AB  - The aim of this study was to examine the interaction of acute atrial fibrillation
      (Af) and acute myocardial infarction (AMI) on left atrial (LA) and left
      ventricular (LV) filling in atrioventricular (A-V) sequential paced, open chest,
      anesthetized dogs. Left atrial conduit function was determined from pulmonary
      venous flow (PVF) and detailed analysis of early diastolic flow with the use of
      micromanometers and transmitral Doppler echocardiography. We studied 8 dogs with
      regular ventricular rates to avoid the confounding effect of ventricular
      arrhythmia in Af. In the control stage, Af increased the diastolic PVF volume to
      the left atrium compared with that during regular A-V pacing (from 0.58 +/- 0.11
      mL/beat to 0.70 +/- 0.13 mL/beat, P <.05), as a compensatory response to the
      impaired systolic PVF volume (from 0.56 +/- 0.12 mL/beat to 0.41 +/- 0.11
      mL/beat, P <.05). As a result, cardiac output was maintained. However, in the AMI
      stage, Af decreased cardiac output (from 0.95 +/- 0.32 L/min to 0.80 +/- 0.23
      L/min, P <.05 versus AMI with A-V pacing), and decreased diastolic PVF volume
      (from 0.46 +/- 0.13 mL/beat to 0.33 +/- 0.14 mL/beat, P <.05 versus AMI with A-V
      pacing). These changes were associated with a prolonged LV isovolumic pressure
      decay rate. Our study demonstrates that Af does not affect cardiac output in the
      setting of normal LV function at a controlled ventricular rate because enhanced
      LA conduit flow compensates for impaired LA reservoir function. In contrast, in
      the setting of AMI, the compensatory response to Af is attenuated because of
      abnormal LV relaxation, resulting in a decrease in cardiac output.

PMID- 11593208
TI  - Harmonic imaging in fetal echocardiography.
AB  - Noncontrast harmonic imaging (HI) has been shown to improve image quality in
      adults with poor acoustic windows. The utility of fetal echocardiography may be
      limited by suboptimal acoustic windows, and the use of HI in fetal
      echocardiography has not previously been defined. The purpose of this study was
      to compare the quality of fundamental imaging (FI) and HI in fetal
      echocardiography. Sixty-two fetal echocardiograms, including 44 (71%) with
      limited acoustic windows, were performed with the use of FI and HI. Image quality
      and visualization of the ventricles, valves, and the aortic and ductal arches
      were evaluated and compared between FI and HI. Mean HI scores were higher than
      mean FI scores for all the structures evaluated. Compared with FI, HI improved
      the image quality and visualization of cardiac structures in this group of
      fetuses with predominantly suboptimal acoustic windows. Harmonic imaging is a
      useful adjunct to FI in echocardiography, and the benefits of HI extend to
      cardiac imaging in the fetus.

PMID- 11593209
TI  - Intramyocardial hematoma mimicking abnormal left ventricular trabeculation.
AB  - Intramyocardial hematoma may present as a tumor or pseudoaneurysm on
      echocardiography. A 68-year-old man was admitted with a subacute posterior wall
      infarction complicated by ventricular fibrillation. Echocardiography showed
      isolated left ventricular abnormal trabeculations, a finding suggesting an
      associated skeletal muscle disorder, in the lateral wall. At cardiac surgery,
      performed 6 weeks later because of severe 3-vessel disease, an intramyocardial
      hematoma of the lateral wall was excised, and myocardial and skeletal muscle
      biopsies were taken, which showed neither isolated left ventricular abnormal
      trabeculations nor skeletal muscle disorder. Postoperatively, echocardiography
      revealed no abnormal trabeculations.

PMID- 11593210
TI  - Giant left atrium secondary to tight mitral stenosis leading to acquired
      Lutembacher syndrome: a case report with emphasis on role of echocardiography in
      assessment of Lutembacher syndrome.
AB  - Lutembacher syndrome is an unusual clinical entity of congenital secundum atrial
      septal defect in combination with rheumatic mitral stenosis. Although this
      classic form is seldom seen by the adult cardiologist, spontaneous Lutembacher
      syndrome as discussed later or the iatrogenic variant is not infrequently
      encountered. The pathophysiologic, clinical, and hemodynamic differences of
      mitral valve disease in the presence of atrial septal defect compared with
      isolated mitral stenosis are highlighted in this case review. Special emphasis
      has also been given to echocardiographic evaluation of this syndrome complex,
      particularly in the setting of percutaneous mitral valvuloplasty, which produces
      the iatrogenic form of Lutembacher syndrome.

PMID- 11593211
TI  - Unusual echocardiographic views of bicuspid and tricuspid pulmonic valves.
AB  - The pulmonary artery is typically seen on transthoracic echocardiography in its
      longitudinal axis. Therefore, short axis views of the pulmonic valve leaflets are
      not generally obtained, and the distinction between tricuspid and bicuspid
      pulmonic valves is difficult or impossible. Bicuspid pulmonic valve is one cause
      of pulmonic stenosis, which is especially common in tetralogy of Fallot.
      Presented here are 2 patients in whom the orientation of the pulmonary artery was
      unusual, and the pulmonic valve was seen en face. The first patient had tetralogy
      of Fallot and a bicuspid pulmonic valve. The severe obstruction to right
      ventricular outflow was infundibular. The second patient had severe stenosis of a
      tricuspid pulmonic valve, which was treated with balloon valvuloplasty. These
      unusual views of the pulmonic valve leaflets were obtained because of anterior
      displacement of the pulmonary artery, and precise anatomic delineation of the
      problem in each case was possible with transthoracic echocardiography.

PMID- 11593212
TI  - Patent foramen ovale presenting as platypnea-orthodeoxia: diagnosis by
      transesophageal echocardiography.
AB  - Platypnea-orthodeoxia is a rare syndrome that is often associated with
      interatrial shunting through a patent foramen ovale or atrial septal defect. We
      describe the case of a 65-year-old woman with progressive dyspnea and hypoxia
      when standing and walking, which was relieved by assuming the recumbent position.
      The diagnosis was confirmed by tilt-table transesophageal echocardiography
      demonstrating a large right-to-left shunt through a patent foramen ovale while
      the patient was in a semiupright position and no significant shunt while in a
      recumbent position. This case demonstrates that platypnea-orthodeoxia caused by a
      patent foramen ovale can be clearly demonstrated by the technique of contrast
      transesophageal echocardiography performed on a tilt table.

PMID- 11593213
TI  - Eustachian valve endocarditis caused by Streptococcus viridans.
AB  - A 76-year-old man was admitted for ethanol detoxification. He was found to be in
      atrial fibrillation with a rapid ventricular response that was refractory to
      electrical and chemical cardioversion attempts. The patient subsequently
      developed respiratory distress. A transesophageal echocardiogram revealed a
      vegetation attached to the eustachian valve and blood cultures grew Streptococcus
      viridans. After treatment with appropriate antibiotics, the patient converted to
      sinus rhythm with sotalol hydrochloride, and the eustachian valve vegetation
      resolved. This is the first reported case of eustachian valve endocarditis caused
      by S viridans.

PMID- 11593214
TI  - Left atrioventricular plane motion response during dobutamine echocardiography.

PMID- 11593216
TI  - The patient behind the image.

PMID- 11593217
TI  - Incidence of major cardiovascular events in black patients with normal myocardial
      stress perfusion study results.
AB  - BACKGROUND: Previous studies have shown that the risk of major cardiovascular
      events at 1 year is less than 1% in patients with normal myocardial stress
      perfusion study results. However, the racial distribution of patients enrolled in
      these studies is not known. Hence, the prognostic value of normal stress
      perfusion study results in black patients is not well established. Our objective
      was to determine the incidence of major cardiovascular events in black patients
      with normal stress perfusion study results over a 12-month period. METHODS AND
      RESULTS: We searched the nuclear cardiology database at our institution for all
      black patients who had normal stress perfusion study results between January 1990
      and December 1996. We excluded patients with a history of coronary
      revascularization, valvular heart disease, cardiomyopathy, congenital heart
      disease, left bundle branch block, or pre-excitation syndrome. Patients were
      followed up for at least 12 months from the time of inclusion. A total of 592
      patients were enrolled and were followed up for 18 +/- 6 months (mean +/- SD). Of
      these, 388 underwent treadmill exercise testing, 155 underwent dipyridamole
      stress testing, and the remainder underwent dobutamine stress testing. Perfusion
      studies were performed in all patients with thallium 201 single photon emission
      computed tomography imaging. During the follow-up period, 11 cardiac deaths and 7
      myocardial infarctions (MIs) occurred. The incidence of cardiac deaths was 1.2%
      per year, and that of nonfatal MIs was 0.8% per year. The total incidence of
      major cardiovascular events was 2% per year. In patients who underwent treadmill
      exercise testing, the incidence of major cardiovascular events was 1% per year.
      Performance of a pharmacologic stress test and a prior MI were significantly
      associated with death or nonfatal MI (P <.05). CONCLUSIONS: The overall incidence
      of major cardiovascular events in black patients after normal exercise perfusion
      study results were obtained was low (1%). However, black patients who had normal
      perfusion study results but underwent pharmacologic stress testing or had a
      history of MI were at intermediate risk. These patients require close
      surveillance for major cardiovascular events.

PMID- 11593218
TI  - Tolerance and diagnostic accuracy of an abbreviated adenosine infusion for
      myocardial scintigraphy: a randomized, prospective study.
AB  - BACKGROUND: The objectives of this study were 2-fold: (1) to determine the
      tolerance of adenosine perfusion tomography with the use of an abbreviated (3
      minute) infusion in comparison to the standard (6-minute) infusion, and (2) to
      assess the relative diagnostic accuracy of a 3-minute adenosine infusion in
      patients referred for arteriography. An abbreviated adenosine infusion may
      decrease the frequency and duration of side effects and be a more cost-effective
      alternative. METHODS AND RESULTS: We prospectively randomized 599 patients
      undergoing adenosine myocardial perfusion tomography to either a 3-minute or 6
      minute adenosine infusion at 140 microg/kg per minute. Among the 599 enrolled
      patients, 142 subsequently underwent coronary angiography. Patients randomized to
      the 3-minute adenosine infusion tolerated the procedure better than those
      randomized to the standard infusion (P <.01). Flushing, headache, neck pain, and
      atrioventricular block were all significantly less frequent (P <.01) with the
      abbreviated infusion. Moreover, patients receiving the abbreviated infusion had
      less hypotension and tachycardia (P <.05). The sensitivity of the test for
      detection of coronary artery disease was 88% for both the 3- and 6-minute
      infusions. In patients with abnormal scan results, perfusion defect size was
      slightly larger in those receiving a 6-minute infusion versus those receiving a 3
      minute infusion (P =.05). CONCLUSIONS: An abbreviated 3-minute adenosine
      infusion, in combination with perfusion tomography, has similar sensitivity for
      detection of coronary artery disease and is better tolerated than the standard 6
      minute infusion.

PMID- 11593219
TI  - Usefulness of distinct activity thresholds according to baseline regional
      asynergy for predicting functional recovery in patients with chronic coronary
      artery disease and left ventricular dysfunction: a study with nitrate-enhanced
      sestamibi gated SPECT.
AB  - BACKGROUND: The role of gated single photon emission computed tomography (SPECT)
      in improving viability detection with the use of perfusion imaging is uncertain.
      This study aimed to verify whether the classification of baseline regional
      dysfunction with gated SPECT helps to predict functional recovery with the use of
      quantitative perfusion imaging. METHODS AND RESULTS: Resting nitrate-enhanced
      sestamibi gated SPECT was performed in 31 patients with left ventricular
      dysfunction, who later underwent coronary revascularization. With the use of a 16
      segment model, tracer activity was quantified, and wall motion and thickening
      were estimated with a 4-point scoring scheme. Reversible dysfunction was assessed
      with follow-up gated SPECT. According to receiver operating characteristic curve
      analysis, the best overall cutoff for predicting reversible dysfunction in
      asynergic segments was 50% of peak activity or greater, with 83% sensitivity, 54%
      specificity, and 64% accuracy. When the segments were divided according to wall
      motion in resting gated SPECT, the optimal activity cutoff was greater than 68%
      for hypokinetic and 50% or greater for adyskinetic segments. With the use of 2
      thresholds, the overall sensitivity remained good (76%), whereas specificity
      increased to 73% (P <.0005) and accuracy to 74% (P <.02). CONCLUSIONS: Regional
      dysfunction assessment directly on perfusion images permits use of different
      activity thresholds with an improvement over a single cutoff for all asynergic
      segments. Therefore combining perfusion and functional data with nitrate-enhanced
      gated SPECT at rest appears to be a promising approach for viability detection.

PMID- 11593220
TI  - Electrocardiographic evolution after Q-wave anterior myocardial infarction:
      correlations between QRS score and changes in left ventricular perfusion and
      function.
AB  - BACKGROUND: In the thrombolytic era, conflicting data have been reported on the
      usefulness of the QRS score in estimating the amount of left ventricular (LV)
      damage after acute myocardial infarction (MI). METHODS AND RESULTS: We correlated
      the QRS score with the extent of LV hypoperfusion and ejection fraction (EF) in
      95 consecutive male patients with a first anterior Q-wave MI; the 6-month
      evolution of QRS score and changes in LV perfusion and function were also
      compared. The Selvester-Wagner QRS score was computed from the digitized 12-lead
      electrocardiogram, both at predischarge and 6 months later; at the same time,
      resting sestamibi first-pass ventriculography and single photon emission computed
      tomography imaging were performed. A reduction in QRS score occurred at 6 months
      (6.7 +/- 3.4 vs 7.8 +/- 2.9 at predischarge; P <.001); the perfusion defect
      extent also decreased (P <.01), and LV EF improved (P <.05). At predischarge, no
      correlation was found between QRS score and hypoperfusion extent or EF; in
      contrast, a weak correlation was observed 6 months later (r = 0.55; P <.001; and
      r = 0.48; P <.01, respectively). QRS score changes from predischarge to 6 months
      showed limited accuracy in predicting clinically meaningful changes of perfusion
      or EF (receiver operating characteristic area under the curve, 0.58 and 0.61,
      respectively). Thrombolytic therapy did not influence the relationship between
      QRS score and scintigraphic findings. CONCLUSIONS: In patients with recent
      anterior Q-wave MI, QRS scoring showed a weak, delayed correlation with the
      amount of LV damage, as estimated by radionuclide techniques. Spontaneous changes
      in QRS score from predischarge to 6 months seem to be of limited value in
      identifying patients with late improvement in LV perfusion and function.

PMID- 11593221
TI  - Assessment of left ventricular diastolic function with electrocardiography-gated
      myocardial perfusion SPECT: comparison with multigated equilibrium radionuclide
      angiography.
AB  - BACKGROUND: Technetium-labeled myocardial perfusion tracers allow the
      simultaneous assessment of myocardial perfusion and left ventricular function by
      electrocardiography (ECG)-gated myocardial perfusion single photon emission
      computed tomography (SPECT). This study evaluates left ventricular systolic and
      diastolic function by ECG-gated SPECT with the use of higher framing (32 frames
      per cardiac cycle) data acquisition. METHODS AND RESULTS: After receiving an
      injection of technetium 99m tetrofosmin, 48 patients with cardiac diseases were
      examined by ECG-gated myocardial perfusion SPECT with a 3-headed gamma camera.
      During gated data collection, 32 frames per cardiac cycle were acquired over 360
      degrees in 60 steps, each of which consisted of 60 beats. Immediately thereafter,
      the 32 frames taken at each projection angle were combined into 16-frame and 8
      frame data sets. Left ventricular end-diastolic volume (LVEDV, in milliliters),
      left ventricular end-systolic volume (LVESV, in milliliters), and left
      ventricular ejection fraction (LVEF, percentage) were automatically calculated
      from the 32-frame, 16-frame, and 8-frame gated data sets. Left ventricular time
      volume curves from the 3 data sets were generated by Fourier curve fitting
      analysis with the use of 3 harmonics, and then peak filling rate (PFR, per
      second) was measured. Twenty-nine patients also underwent multigated equilibrium
      radionuclide angiography (ERNA) to determine the LVEF and PFR. Combining the 32
      frame data into 16-frame and 8-frame data sets from the 48 patients generated a
      smaller LVEDV and a larger LVESV, and LVEF was significantly lower in accordance
      with the decreasing number of frames. Compared with ERNA studies (n = 29), the
      Bland-Altman method showed underestimated LVEFs and larger 95% limits of
      agreement in lower framing gated SPECT. CONCLUSIONS: Left ventricular functional
      parameters obtained from 32-frame gated SPECT correlated closely with those
      determined by ERNA studies. ECG-gated SPECT with 32-frame data can provide
      comprehensive information with which to evaluate many types of cardiac diseases.

PMID- 11593222
TI  - Estimation of coronary flow reserve with the use of dynamic planar and SPECT
      images of Tc-99m tetrofosmin.
AB  - BACKGROUND: We developed a noninvasive method to examine coronary flow reserve
      with technetium 99m tetrofosmin based on the microsphere model. According to the
      microsphere model, myocardial blood flow (MBF) can be calculated by MBF = q /
      integral C(t)dt, where q is myocardial activity and C(t) is tracer concentration
      in blood. Because the ratio of integral C(t)dt at stress to rest is equal to the
      ratio of the first transit count in the pulmonary artery (PA) and attenuation
      factors were canceled out, we calculated the increase ratio of MBF (MBF(IR)).
      METHODS AND RESULTS: After injection of dipyridamole, tetrofosmin was injected as
      a bolus and serial dynamic planar images were obtained to measure the first
      transit count in PA (PAC). Myocardial single photon emission computed tomography
      was performed to measure the regional myocardial count (RMC). MBF(IR) was
      calculated as [(RMCs x PACr)/(RMCr x PACs) - 1] x 100, where r and s denote
      resting and stress conditions, respectively. In contrast, the increase in the
      myocardial uptake ratio (MUR(IR)) was defined as (RMCs x SCr/RMCr x SCs - 1) x
      100, where SC is syringe count of tracer. The results were as follows: (1) The
      mean MBF of healthy subjects was 46.9% +/- 22.8%. (2) MBF(IR) of the infarcted
      region and ischemic region was significantly decreased (8.3% +/- 12.2% and 11.2%
      +/- 11.9%, respectively; P <.001). (3) MUR(IR) was significantly lower than
      MBF(IR) (14.1% +/- 21.2%; P <.001). (4) MBF(IR) decreased according to the heart
      rate at rest (r = 0.47; P <.05). CONCLUSIONS: MBF(IR) is a potential parameter
      with which to evaluate coronary flow reserve when the changes of arterial input
      function during stress are considered.

PMID- 11593223
TI  - A precise, three-dimensional atlas of myocardial perfusion correlated with
      coronary arteriographic anatomy.
AB  - To map precise myocardial perfusion anatomy, we correlated detailed coronary
      arteriographic anatomy for every coronary artery and all secondary branches in
      the heart that had flow-limiting stenosis with corresponding specific,
      circumscribed, myocardial perfusion defects by positron emission tomography.
      Eight hundred ninety-five patients with abnormal coronary arteriograms showing
      any visible coronary artery narrowing of greater than 10% diameter stenosis
      underwent positron emission tomography perfusion imaging at rest and after
      dipyridamole stress; the data obtained were processed automatically into 3
      dimensional topographic displays of relative radionuclide uptake in anterior,
      septal, left lateral, and inferior quadrant views, without attenuation artifacts,
      depth-dependent resolution, or spatial distortion of polar displays. The
      selection criterion for detailed anatomic analysis was the presence of a
      discrete, localized, moderate to severe, dipyridamole-induced perfusion defect,
      defined by automated algorithms as 1 quadrant view outside 2 SDs of healthy
      control subjects with which a specific stenotic coronary artery and/or its
      secondary branches could be correlated unequivocally on the coronary arteriogram
      for mapping precise perfusion anatomy, not for determining sensitivity or
      specificity. Because the anatomy of myocardial perfusion is inherently not
      statistical data, the results are presented as a summary atlas and series of
      individual cases that illustrate myocardial perfusion anatomy. Because the
      patterns of myocardial perfusion anatomy were derived from a large number of
      subjects, the atlas provides generalized information, not previously published,
      that correlates detailed arteriographic anatomy with perfusion anatomy including
      secondary diagonal, marginal, and posterior descending branches of the coronary
      arteries.

PMID- 11593224
TI  - Manipulating the mouse genome: approaches and applications.

PMID- 11593226
TI  - Radionuclide monitoring of left ventricular function.

PMID- 11593225
TI  - Regulation of the coronary vasomotor tone: What we know and where we need to go.
AB  - The control of coronary blood flow has been studied for decades, but despite our
      extensive efforts, the critical regulators of flow are largely unknown. One
      purpose of this review is to summarize some recent concepts about the control of
      coronary flow and also point out areas where additional knowledge must be
      acquired. A second purpose of this review is to highlight the need for additional
      noninvasive measurements of flow that undoubtedly will require further evolution
      of contemporary technologies, and also application of specific methods toward
      noninvasive measurements of coronary blood flow. Only after the development of
      such measurements will the scientific community begin to understand the
      intricacies of the regulation of coronary flow in human beings.

PMID- 11593227
TI  - Volatility in the diagnostic markets: is there a "new economy" of testing?

PMID- 11593228
TI  - Estimation of coronary flow reserve: can SPECT compete with other modalities?

PMID- 11593229
TI  - Racial disparities in cardiovascular health care: unfulfilled exSPECTations?

PMID- 11593230
TI  - Use of gated SPECT to identify a case in which tracer activity arising from the
      right ventricular free wall led to overestimation of the amount of viability
      within the septal wall.

PMID- 11593231
TI  - Rectal prolapse.

PMID- 11593232
TI  - GDNF acutely modulates excitability and A-type K(+) channels in midbrain
      dopaminergic neurons.
AB  - Glial cell line-derived neurotrophic factor (GDNF) prevents lesion-induced death
      of midbrain dopaminergic neurons, but its function in normal brain remains
      uncertain. Here we show that GDNF acutely and reversibly potentiated the
      excitability of cultured midbrain neurons by inhibiting transient A-type K(+)
      channels. The effects of GDNF were limited to large, tyrosine hydroxylase (TH)
      positive dopaminergic neurons, and were mediated by mitogen associated protein
      (MAP) kinase. Application of GDNF also elicited a MAP kinase-dependent
      enhancement of the excitability in dopaminergic neurons in midbrain slice. These
      results demonstrate an acute regulation of GDNF on ion channels and its
      underlying signaling mechanism, and reveal an unexpected role of GDNF in normal
      midbrain dopaminergic neurons.

PMID- 11593233
TI  - Visualizing synapse formation in arborizing optic axons in vivo: dynamics and
      modulation by BDNF.
AB  - Dynamic developmental changes in axon arbor morphology may directly reflect the
      formation, stabilization and elimination of synapses. We used dual-color imaging
      to study, in the live, developing animal, the relationship between axon
      arborization and synapse formation at the single cell level, and to examine the
      participation of brain-derived neurotrophic factor (BDNF) in synaptogenesis.
      Green fluorescent protein (GFP)-tagged synaptobrevin II served as a marker to
      visualize synaptic sites in individual fluorescently labeled Xenopus optic axons.
      Time-lapse confocal microscopy revealed that although most synapses remain
      stable, synapses are also formed and eliminated as axons branch and increase
      their complexity. Most new branches originated at GFP-labeled synaptic sites.
      Increasing BDNF levels significantly increased both axon arborization and synapse
      number, with BDNF increasing synapse number per axon terminal. The ability to
      visualize central synapses in real time provides insights about the dynamic
      mechanisms underlying synaptogenesis, and reveals BDNF as a modulator of
      synaptogenesis in vivo.

PMID- 11593234
TI  - Temporal and rate representations of time-varying signals in the auditory cortex
      of awake primates.
AB  - Because auditory cortical neurons have limited stimulus-synchronized responses,
      cortical representations of more rapidly occurring but still perceivable stimuli
      remain unclear. Here we show that there are two largely distinct populations of
      neurons in the auditory cortex of awake primates: one with stimulus-synchronized
      discharges that, with a temporal code, explicitly represented slowly occurring
      sound sequences and the other with non-stimulus-synchronized discharges that,
      with a rate code, implicitly represented rapidly occurring events. Furthermore,
      neurons of both populations displayed selectivity in their discharge rates to
      temporal features within a short time-window. Our results suggest that the
      combination of temporal and rate codes in the auditory cortex provides a possible
      neural basis for the wide perceptual range of temporal information.

PMID- 11593235
TI  - Sinus pericranii in the frontal region: a case report.
AB  - Sinus pericranii is a rare vascular anomaly. A case of sinus pericranii at the
      nasion with an orbital extension is presented. The drainage was into the superior
      sagittal sinus. The pathogenesis is discussed and the literature is reviewed.

PMID- 11593236
TI  - Motor and somatosensory evoked potentials in a primate model of experimental
      spinal cord injury.
AB  - Motor and somatosensory evoked potentials (MEP and SSEP) were compared after
      experimental spinal cord injury in Bonnet monkeys (macaca radiata). The MEP and
      SSEP changes following graded injuries were related to clinical outcome. Eight
      healthy mature monkeys with a mean weight of 4.2 + 0.9 Kg were chosen for the
      study. Graded spinal cord injury was caused using 50, 100, 200, 300 gm-cm force
      by modified Allens' weight drop device. MEP and SSEP recordings were done before
      injury and at 0, 2, 4 and 6 hours after injury and on the 7th postoperative day.
      Neurological assessment was done at 24 hours and on the 7th day following injury.
      50, 100, 200 gm-cm force caused partial injuries and 300 gm-cm force caused
      severe spinal cord injury. The predictive value of MEP and SSEP following partial
      injuries was 80% and 66.67% respectively. Both MEP and SSEP were 100% predictive
      in severe injury. MEP and SSEP monitoring can therefore be complementary to each
      other in predicting the neurological outcome in partial injuries to the spinal
      cord.

PMID- 11593237
TI  - Micro embolic signals in patients with cerebral ischaemic events.
AB  - The aim of this study was to evaluate the occurrence of micro embolic signals
      (MES) in patients with a cerebral ischaemia using transcranial doppler monitoring
      and to find out its diagnostic relevance. We prospectively performed bilateral
      multigated transcranial doppler monitoring from both middle cerebral arteries in
      359 patients with an acute or recent (<4 weeks) cerebral ischaemic event, and in
      182 control subjects without a cerebral ischaemic event. MES were analysed
      according to the standardised protocol. Patients with cerebral ischaemic events
      had a significantly higher (p<0.00001) rate of MES occurrence (31.8%) than
      control subjects (5.5%). MES were detected significantly higher in patients with
      partial or total anterior circulation infarcts (39.1%) than in those with lacunar
      infarcts (26.0%) or transient ischaemic attacks (27.3%). A correlation of MES and
      neuroimaging finding was also tried. TCD was found to have a predictive role in
      microemboli monitoring, predominantly in patients with large vessel territory
      infarction.

PMID- 11593238
TI  - Intracranial haemorrhage resulting from unsuspected choriocarcinoma metastasis.
AB  - A retrospective analysis of clinicopathological data of 10 patients with
      clinically unsuspected cerebral metastatic choriocarcinoma was carried out. All
      patients were young adult females. History of preceding pregnancy/abortion was
      forthcoming in 5 cases but none had a prior history of abnormal gestation.
      Features of raised intracranial tension followed by hemiparesis were the
      commonest presenting symptoms. A clinicoradiologic diagnosis of intracerebral
      haemorrhagic mass, either primary or secondary to tumour bleed, cortico-venous
      thrombosis or arteriovenous malformation, was entertained in 8 out of 10 cases.
      In other two cases, ring enhancing lesions prompted the diagnosis of
      granulomatous masses. Eight patients were operated upon, of whom two died after
      short hospital stay, and were autopsied. All had haemorrhagic masses noted at
      surgery/autopsy. Accurate diagnosis of metastatic choriocarcinoma was established
      only by histologic examination of these haemorrhages. This report emphasizes the
      importance of considering metastatic choriocarcinoma as an important differential
      diagnosis of haemorrhagic intracerebral lesions in women of child bearing age
      group. Measurement of serum/CSF level of HCG in suspected cases helps to
      implement early therapy. The diagnostic value of histopathologic examination of
      surgically resected blood clots in determining aetiology of intracerebral
      haemorrhagic masses is highlighted.

PMID- 11593239
TI  - Cysts of the central nervous system : a clinicopathologic study of 145 cases.
AB  - Non-neoplastic, non-inflammatory cysts of the central nervous system may cause
      symptoms because of pressure, rupture or secondary inflammation. A total of 145
      cases of cysts were reviewed during a study period of 12 years. The clinical
      details and histological features were noted in all cases. During this period 53
      epidermoid cysts, 16 dermoid cysts, 38 colloid cysts, 23 arachnoid cysts, 5
      neurenteric cysts, 5 ependymal and glial cysts, 2 Rathke's cleft cysts and 3
      unclassified cysts were encountered. The possible histogenesis is also discussed.

PMID- 11593240
TI  - Spinal congenital dermal sinus: an experience of 23 cases over 7 years.
AB  - Spinal congenital dermal sinus is a rare entity, which supposedly results from
      the failure of neuroectoderm to separate from the cutaneous ectoderm during the
      process of neurulation. The present study was undertaken to know the clinical
      profile of these patients, to study associated anomalies and to assess the
      results of surgical intervention. We had 23 patients with male : female ratio of
      9:16. Only 2 patients were below 2 years of age and most cases (16) were between
      2-16 years (mean age =10.2 years). Lumbar region (17 cases) was most frequently
      involved, followed by lumbosacral and thoracic region in 3 patients each. Only
      three patients were asymptomatic at the time of presentation. Most of the cases
      presented with evidence of neural compression or tethered cord syndrome. Only one
      case presented with spinal abscess. The motor, sensory and autonomic deficits
      were seen in 20, 11 and 12 patients respectively. Scoliosis and CTEV (congenital
      talipus equino varus) were the common associated anomalies. MRI revealed
      associated dysraphic state of spinal cord in 21(>90%) cases. All patients
      underwent surgical exploration and repair of dysraphic state and excision of the
      sinus. None of the asymptomatic patients deteriorated. Overall 8 patients
      improved, 14 got their neurological status stabilized, including 3 asymptomatic
      cases. Only one patient deteriorated. Postoperative wound infection was seen in 2
      cases. As age advances, the chance of developing neurological deficit increases.
      Associated dysraphic state should be looked for and treated simultaneously, using
      microsurgical technique, whenever possible. It is better to treat all these cases
      with aggressive surgical intervention before the neurological deficits appear.

PMID- 11593241
TI  - Single flap fronto-temporo-orbito-zygomatic craniotomy for skull base lesions.
AB  - Surgery was performed, through single flap fronto-temporo-orbito-zygomatic
      approach in 22 patients with skull base lesions. In two of these patients, this
      approach was combined with a transpetrosal approach. The pathological spectrum
      consisted of trigeminal neurofibromas (5), spheno-orbital meningiomas (4),
      carotico-ophthalmic aneurysms (4), basilar top aneurysms (2), cavernous sinus
      haemangiomas (2), invasive pituitary tumours (2) and one patient each of
      metastatic adenocarcinoma of the cavernous sinus, transcranial fungal granuloma
      and tubercular granuloma of the cavernous sinus. Of the 14 tumours, 10 were
      excised totally/near totally while a subtotal excision was achieved in four.
      Removal of the anterior clinoid process facilitated the clipping of all the
      carotico-ophthalmic aneurysms. One basilar top aneurysm was wrapped and the other
      clipped. One patient of fungal granuloma died of fungal meningitis and one
      patient of basilar top aneurysm expired as a result of thalamic infarct. The
      advantages of this approach included excellent exposure of the skull base
      lesions, making the dissection distance shorter and wider, minimal brain
      retraction and easy replacement of the single bone flap.

PMID- 11593242
TI  - Extended frontobasal approach to the skull base.
AB  - The extended frontobasal approach provides an adequate midline exposure from the
      anterior cranial fossa to the sphenoclival region. Between November 1991 and
      August 1999, 13 patients with extensive anterior and anterolateral skull base
      tumours extending to supra and parasellar regions, cavernous sinus and
      sphenoclival regions were operated upon using this approach alone (7 patients) or
      in combination with subtemporal -infratemporal (4 patients) or transfacial (2
      patients) approaches. Gross total excision was performed in 8 patients while in 4
      patients with malignant tumours and in a patient with extensive skull base fungal
      granuloma, only partial excision was possible. Basal repair was performed using
      pedicled pericranium, temporalis muscle or fascia lata. The complications
      included increase in the cranial nerve paresis, endophthalmitis, facial oedema,
      CSF leak, frontal haematoma and internal carotid artery injury. This study
      reviews the operative technique, the indications and the complications of
      extended frontobasal approach.

PMID- 11593243
TI  - Intracranial infective aneurysms: angiographic evaluation with treatment.
AB  - Infective intracranial aneurysms are relatively uncommon. They develop due to
      septic embolisation of the vasa vasorum or lumen of the artery, with resultant
      focal arteritis and necrosis, leading to aneurysm formation. They are an
      important cause for intracranial haemorrhage. Six cases of infective aneurysms
      are described. A focus of infection could be detected in all the patients.
      Surgery was done in three cases, out of which two patients made significant
      recovery, while one patient died in the immediate postoperative period. Out of
      the three cases, treated conservatively with antibiotic therapy, there was total
      resolution on follow up angiogram in two, while one patient was lost to follow
      up.

PMID- 11593244
TI  - Effect of methyl prednisolone on sensory motor functions in tuberculous
      meningitis.
AB  - A prospective hospital based study was undertaken to study the effect of methyl
      prednisolone therapy on sensory and motor functions in tuberculous meningitis
      (TBM). The patients with TB meningitis seen during 1994-1998 were studied. CT
      scan, motor evoked potential (MEP) to upper and lower limbs; and median and
      tibial somatosensory evoked potentials (SEP) were carried out in all the
      patients. Outcome was defined at the end of 3 months into poor, partial or
      complete recovery on the basis of Barthel index score. Inj methyl prednisolone
      (MPS) 500 mg IV was given to 21 patients followed by oral tapering dose of
      prednisolone over one month in addition to 4 drug anti-tubercular treatment. The
      control group comprised of 16 patients who received 4 drugs anti-tubercular
      therapy without any corticosteroid. These groups were comparable with respect to
      their age, stage of meningitis, Glasgow coma scale score and radiological
      findings. In MPS group, CMCT was abnormal in 9 and SEPs in 7 patients. In the
      control group, these were abnormal in 9 and 5 patients respectively. Three months
      after the therapy the frequency of improvement, deterioration and stationary
      evoked potential (EP) changes were also noted in both the groups. Diversity of
      evoked potential changes were also noted. Evoked potential changes were neither
      significantly different between the groups nor there was any beneficial effect
      shown in MPS group at 3 months. On the contrary, the control group fared
      significantly better than the MPS group. Initial MEP and SEP abnormalities were
      however related to 3 months outcome (p<0.01).

PMID- 11593245
TI  - A study of factors delaying hospital arrival of patients with acute stroke.
AB  - Thrombolytic therapy for acute ischaemic stroke has recently become available in
      India but its success depends on initiating the treatment in the narrow
      therapeutic time window. There is commonly a delay of several hours before
      patients with acute stroke seek medical attention. A prospective study was
      conducted to assess the factors influencing this delay in admission of acute
      stroke cases. 110 cases (71 males, 39 females) of acute stroke that arrived
      within 72 hours at our hospital casualty were recruited. A standardized
      structured questionnaire was given to patients or their attendants. The median
      time to casualty arrival was 7.66 hours with 25% cases arriving within 3 hours
      and 49 % cases within 6 hours. Distance from hospital, contact with a local
      doctor and low threat perception of symptoms of stroke were independent factors
      associated with delay in arrival. Living in city, presence of family history and
      older age were associated with early arrival. There was no correlation with
      patients' or attendants' sex, educational status, history of previous stroke or
      transient ischaemic attack, subtype or severity of stroke, time of stroke and
      availability of transport. Adequate measures need to be taken to improve the
      public awareness of stroke and the role of local doctors.

PMID- 11593246
TI  - Vasculitic neuropathy in HIV infection: a clinicopathological study.
AB  - Vasculitis causing peripheral neuropathy may be the first sign of HIV infection.
      We report four such cases in whom the onset of peripheral neuropathy led to the
      detection of HIV infection. Two patients presented with features of mononeuritis
      multiplex, while the other two had a lumbosacral polyradiculopathy. A prior
      history of blood transfusion was forthcoming in one of the patients. Sural nerve
      biopsies in all the four cases and the muscle biopsy in two, histologically
      showed evidence of vasculitis. Immunohistochemically, the viral antigen was not
      demonstrable in any of the biopsies, but on electron microscope, virus-like
      particles were identifiable in the Schwann cell cytoplasm and the perivascular
      macrophages in one case. To the best of our knowledge, this is the only report
      that has documented the virus in the Schwann cells as well as the perivascular
      macrophages lending credence to the fact that these viruses are neurotropic as
      well as lymphotropic. Immunoglobulin deposits were not demonstrable in any of the
      cases, suggesting that direct viral invasion may have a role in the pathogenesis
      of peripheral nerve vasculitis.

PMID- 11593247
TI  - Serum cobalamin levels in dementias.
AB  - The present study attempts to find a correlation between low serum B-12 levels
      and dementias. A total of 178 patients of dementia were seen at the cognitive
      disorder clinic from 1996 to 1998. Serum B-12 levels were studied in 100
      patients. 15 patients (39.5%) of Alzheimer's dementia had reduced B-12 levels,
      while only 5 patients (13.9%) with vascular dementias and 3 patients (11.5%) with
      other types of dementias had reduced levels. The incidence of low serum B-12 was
      statistically significant in the Alzheimer's group when compared with the other
      groups, individually as well as combined together (p<0.05). The aetiopathogenesis
      and significance of these findings is discussed and the literature is reviewed.

PMID- 11593248
TI  - Febrile status epilepticus as the first presentation of cortical developmental
      malformation: report of 2 cases.
AB  - Cortical developmental malformations are an important cause for epilepsy. The
      epileptic disorder usually begins with sporadic seizures, followed by gradually
      increasing seizure frequency and culminating in epilepsia partialis continua. We
      report the de-novo occurrence of focal status epilepticus accompanying
      hyperpyrexia in two male children, aged 18 months and 4 years. One child had
      prior neuro-developmental delay, while in the other, developmental milestones
      were normal. In both instances, there were no seizures prior to the presenting
      neurological illness. Cerebrospinal fluid examination was normal in both the
      cases. Magnetic resonance imaging revealed extensive pachygyria in one patient
      and focal cortical thickening in the other. Therefore, cortical developmental
      malformation may be suspected as an underlying aetiology in children presenting
      with de-novo status epilepticus and hyperpyrexia.

PMID- 11593249
TI  - Disappearing cystic cerebellar medulloblastoma: the ghost tumour.
AB  - A case of medulloblastoma, which disappeared following steroid administration and
      a single sitting of radiotherapy (8Gy) is presented. At surgical exploration
      tumour was not found, multiple biopsies were negative. Post operative CT scan too
      did not show the tumour. Five months later, tumour reappeared in left cerebellar
      lobe in cystic and solid form. Patient was reoperated and tumour was
      decompressed. The biopsy showed medulloblastoma. To our knowledge,
      medulloblastomas are not known to be completely responsive to either of these
      modalities.

PMID- 11593250
TI  - Traumatic distal anterior cerebral artery aneurysm in a child: a case report.
AB  - Traumatic intracranial aneurysms constitute less than 1% of all intracranial
      aneurysms. A case of traumatic distal anterior cerebral artery aneurysm in 18
      months old child, treated successfully by microsurgical excision of aneurysm is
      being reported, along with review of the literature.

PMID- 11593251
TI  - Pituitary tuberculoma--a case report.
AB  - Pituitary tuberculomas, mimicking adenomas are very unusual. We describe a rare
      case of a patient with an exclusively intrasellar mass, and who presented with
      severe headaches and loss of libido. The lesion was approached trans-sphenoidally
      and pathological examination revealed a tuberculoma. Complete removal was
      achieved and the patient followed on anti-tuberculous therapy.

PMID- 11593252
TI  - Intramedullary neurenteric cyst in mid thoracic spine in an adult: a case report.
AB  - Neurenteric cysts are very rare, particularly in adults. These are congenital
      intraspinal cysts of endodermal origin. A 67 years old man, presenting with
      backache and paraesthesiae of one and half years' duration, followed by subacute
      flaccid paraplegia, developing in a week is described. MRI revealed
      intramedullary cyst at T7. He underwent emergency thoracic laminectomy and
      complete excision of the cyst. Histopathology confirmed a neurenteric cyst. In
      view of their rarity, peculiarity in terms of age, location and presentation, we
      report this case.

PMID- 11593253
TI  - Dural arteriovenous malformation: a rare cause of epilepsy in childhood.
AB  - A 3 year and 6 month old girl with epilepsy associated with dural arteriovenous
      malformation (DAVM), diagnosed on the MRI, is presented to emphasise the
      importance of DAVM in the aetiology of childhood epilepsy.

PMID- 11593254
TI  - Reversible posterior leukoencephalopathy syndrome: a report of 2 cases.
AB  - Reversible posterior leukoencephalopathy syndrome (RPLE) is an increasingly
      recognised disorder, most commonly associated with malignant hypertension,
      toxaemia of pregnancy or the use of immunosuppressive agents. Two cases of RPLE
      syndrome occurring in the setting of accelerated hypertension and eclampsia are
      described. Both patients had seizures, altered sensorium and typical findings on
      neuroimaging. They had complete clinical and radiological recovery. The clinical
      course, pathophysiology and neuroimaging features of RPLE syndrome are discussed.

PMID- 11593255
TI  - Suprasellar tuberculoma presenting with diabetes insipidus and hypothyroidism--a
      case report.
AB  - Suprasellar tuberculomas are exceptionally rare and are even rarer in children. A
      case of suprasellar tuberculoma in a five year old male child who presented with
      diabetes insipidus, hypothyroidism and visual field defect is described. Deranged
      CSF parameters, imaging findings of a suprasellar rounded, peripherally enhancing
      lesion with thickening of the pituitary stalk, led to an accurate diagnosis of
      tuberculosis. The patient responded well to antituberculous treatment and an
      unnecessary surgery was avoided.

PMID- 11593256
TI  - Lorazepam: an adjuvant therapy in patients with seizure and heliotaxis.
AB  - Photosensitive epilepsy is a type of reflex epilepsy. Five percent of epileptics
      are photosensitive, i.e. they show photoconvulsive response (PCR) during
      intermittent photic stimulation. Patients with photogenic or photosensitive
      epilepsy have seizures with flickering light. They also exhibit heliotaxis.
      Sodium valproate and ethosuximide are the common drugs used. Even though
      benzodiazepines are useful, the specific effect of lorazepam is not mentioned. We
      report 5 cases of photosensitive epilepsy with inadequate response to usual
      antiepileptic drugs who had complete or near complete remission with lorazepam.

PMID- 11593257
TI  - Reversible neurologic manifestations after glycerol: a short report.
AB  - A 46 year old male inadvertently consumed 500 ml of glycerol and presented with
      altered sensorium, focal neurologic signs and generalised seizures. He was
      managed conservatively and recovered fully within 48 hours. The case highlights
      the rare presentations of overdosage and neurologic effects with glycerol, an
      otherwise safe drug used in neurology.

PMID- 11593258
TI  - Acute transverse myelitis following electrical injury: a short report.
AB  - We report a 30 years lady who developed transverse myelitis following an
      accidental electric shock and later recovered completely.

PMID- 11593259
TI  - Cerebellopontine angle meningioma with acquired chiari and syringomyelia:
      neuroimage.

PMID- 11593260
TI  - Frontopolar and anterior temporal cortex activation in a moral judgment task:
      preliminary functional MRI results in normal subjects.
AB  - OBJECTIVE: To study the brain areas which are activated when normal subjects make
      moral judgments. METHOD: Ten normal adults underwent BOLD functional magnetic
      resonance imaging (fMRI) during the auditory presentation of sentences that they
      were instructed to silently judge as either "right" or "wrong". Half of the
      sentences had an explicit moral content ("We break the law when necessary"), the
      other half comprised factual statements devoid of moral connotation ("Stones are
      made of water"). After scanning, each subject rated the moral content, emotional
      valence, and judgment difficulty of each sentence on Likert-like scales. To
      exclude the effect of emotion on the activation results, individual responses
      were hemodynamically modeled for event-related fMRI analysis. The general linear
      model was used to evaluate the brain areas activated by moral judgment. RESULTS:
      Regions activated during moral judgment included the frontopolar cortex (FPC),
      medial frontal gyrus, right anterior temporal cortex, lenticular nucleus, and
      cerebellum. Activation of FPC and medial frontal gyrus (BA 10/46 and 9) were
      largely independent of emotional experience and represented the largest areas of
      activation. CONCLUSIONS: These results concur with clinical observations
      assigning a critical role for the frontal poles and right anterior temporal
      cortex in the mediation of complex judgment processes according to moral
      constraints. The FPC may work in concert with the orbitofrontal and dorsolateral
      cortex in the regulation of human social conduct.

PMID- 11593261
TI  - Internal carotid artery stenosis: comparison of duplex scan and magnetic
      resonance angiography with digital subtraction angiography.
AB  - OBJECTIVE: We compare duplex scan (DS) and magnetic resonance angiography (MRA)
      with digital angiography (DGA) in respect to accuracy in measuring internal
      carotid artery (IC) stenosis in symptomatic patients. METHOD: Ten symptomatic
      patients with IC stenosis greater than 70% previously diagnosed by DS were
      submitted to another DS and to both MRA and DGA. Both ICs from each patient
      (total 20 ICs) were evaluated by physicians blinded for the results of other
      tests. DS and MRA were compared with DGA, using the intraclass correlation
      coefficient (r) and its 95% confidence interval (95% ci). For each diagnostic
      test, the study group (20 Ics) was also divided in surgical patients (IC stenosis
      between 70 and 99%) and non surgical patients, using kappa concordance
      coefficient (k) to compare the results. RESULTS: Main comparisons are: DS and
      DGA, r = 0.71 (0.4 - 0.87); MRA and DGA, r = 0.61 (0.25 - 0.82). After division
      into surgical vs. non-surgical groups, k = 0.857 (p < 0.0001) between DS and DGA;
      and k = 0.545 (p = 0.003) between MRA and DGA. Most DS and MRA errors occurred in
      IC sub-occlusions. CONCLUSION: The results suggest that when they are used
      together, DS and non-contrast MRA may substitute DGA in the evaluation of
      patients for IC stenosis surgery, except when there is discordance between their
      results or when the methods show sub-occlusive stenosis.

PMID- 11593262
TI  - Comparison between the NASCET method and subjective visual impression in the
      evaluation of internal carotid artery stenosis.
AB  - OBJECTIVE: To evaluate the accuracy of subjective visual impression (SVI) of an
      experienced neuro-radiologist in the measurement of the degree of internal
      carotid artery (IC) stenosis evaluated by digital angiography (DGA). METHOD: Ten
      symptomatic patients with internal carotid stenosis greater than 70% in a
      previous duplex scan were submitted to DGA. The degree of stenosis in both sides
      (symptomatic and asymptomatic) were evaluated by the same neuro-radiologist who
      gave his SVI and applied the NASCET method immediately after. Both methods were
      compared using the intraclass correlation coefficient (r) and its 95% confidence
      interval (95% ci). For each method, the sample (20 ICs) was also divided in
      surgical (stenosis between 70 and 99%) and non surgical ICs, using kappa
      concordance coefficient (k) to compare the results. RESULTS: The results
      comparing the 20 values obtained by each method are: r = 0.90 (95% ci: 0.77
      0.96). Dividing the sample in surgical and non surgical ICs, k = 0.857, p <
      0.0001; sensitivity = 100% (39.6%-100%); specificity = 93.8% (67.7%-99.7%);
      positive predictive value = 80% (29.9%-98.9%); negative predictive value = 100%
      (74,7%-100%). CONCLUSION: The SVI may be used by at least some experienced
      neuroradiologists as a preliminary tool to evaluate the degree of IC stenosis
      with DGA, but a standardised and well established method should be routinely
      performed.

PMID- 11593263
TI  - Risk factors and outcome in 100 patients with aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Clinical and surgical outcome of patients with subarachnoid hemorrhage
      (SAH) due to ruptured aneurysm were assessed in comparison to pre-operative data
      and risk factors such as previous medical history, clinical presenting condition,
      CT findings and site of bleeding. METHODS: We evaluated 100 consecutive patients
      with aneurysmal SAH. Gender, color, history of hypertension, smoking habit, site
      and size of aneurysm, admittance and before surgery Hunt Hess scale, need for
      cerebro-spinal fluid shunt, presence of complications during the surgical
      procedure, Glasgow Outcome Scale, presence of vasospasm and of rebleeding were
      assessed and these data matched to outcome. For statistical analysis, we applied
      the chi-squared test or Fisher's test using the pondered kappa coefficient.
      Kruskal-Wallis test was used for comparison of continue variables. Tendency of
      proportion was analyzed through Cochran-Armitage test. Significance level adopted
      was 5%. RESULTS: Patients studied were mainly white, female, without previous
      history of hypertension and non-smokers. Upon hospital admittance, grade 2 of
      Hunt-Hess scale was most frequently observed (34%), while grade 3 of Fisher scale
      was the most prevalent. Single aneurysms were most frequent at anterior
      circulation, between 12 and 24 mm. The most frequent Glasgow Outcome Scale
      observed was 5 (60%). Hunt Hess upon the moment of surgery and presence of
      complications during surgical procedure showed positive correlation with clinical
      outcome (p=0.00002 and p=0.001, respectively). Other variables were not
      significantly correlated to prognosis. Tendency of proportion was observed
      between Hunt-Hess scale and Fisher scale. CONCLUSION: Among variables such as
      epidemiological data, previous medical history and presenting conditions of
      patients with ruptured aneurysms, the Hunt-Hess scale upon the moment of surgery
      and the presence of surgical adversities are statistically related to degree of
      disability.

PMID- 11593264
TI  - Myasthenia gravis in children: analysis of 18 patients.
AB  - Myasthenia gravis (MG) in childhood is rare comprising 10 to 20 % of all
      myasthenic patients. We studied 18 patients with MG whose first symptoms started
      from 1 to 12 years of age, followed at the Department of Neurology of the UNIFESP
      EPM, from January 1983 to August 1997. There were 10 girls and 8 boys (1.2:1).
      Eleven patients (61%) presented moderate or severe generalized disease and 4
      (22%) had at least one myasthenic crisis. EMG with supramaximal repetitive nerve
      stimulation was diagnostic in 8 (47%) out of 17 patients, and chest CT was normal
      in 14 patients. Seropositivity to acetylcholine receptor antibodies was found in
      81.6% (9 out of 11 tested) and the levels had no relation to clinical severity.
      Nine out of 16 patients (56%) worsened with pyridostigmine alone and were treated
      with prednisone. Four out of those nine continued worsening despite steroids and
      were subjected to thymectomy (all showed thymic lymphoid follicular hyperplasia).
      Three patients (75%) improved markedly after thymectomy and one (25%) worsened,
      eventually getting better with intravenous immunoglobulin and oral azathioprine.
      MG treatment, using all resources available, has to be individualized for each
      child.

PMID- 11593265
TI  - Focusing on dissociated motor development in Brazilian children.
AB  - Dissociated motor development (DMD) is considered when the baby starts
      independent walking late, with normality of the other fields of development.
      There is evidence that babies with DMD present an atypical crawling pattern and
      hypotonia. To investigate the frequency and characteristics of DMD, neurological
      examination was performed monthly in 177 healthy full-term babies from 6 months
      age, in urban and rural zone samples in Brazil. Among 20 children with atypical
      crawling, none presented hypotonia neither did they start independent walking
      late. The means of the ages at the beginning of atypical crawling and independent
      walking acquisitions, 7.40 mo (SD 1.4) and 12.76 mo (SD 2.5) respectively, did
      not differ from the group with crossed crawling pattern. Thus, in this sample of
      Brazilian healthy children we did not find cases with DMD.

PMID- 11593266
TI  - Developmental milestones of vertically HIV infected and seroreverters children:
      follow up of 83 children.
AB  - The aim of the study was to detect neurological abnormalities in human
      immunodeficiency virus (HIV) infected children. This was achieved by a
      prospective evaluation, from November/1995 to April/2000, of 43 HIV infected
      children (group I) and 40 HIV seroreverters children (group II) through
      neurological exam and neurodevelopmental tests: Denver Developmental Screening
      Test (DDST) and Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone
      Scale (CAT/CLAMS). A control group (III), of 67 children, were evaluated by
      CAT/CLAMS. Hyperactivity, irritability and hypotonia were the findings on
      neurological examination, without statistical differences between group I and II.
      On CAT/CLAMS, the group I developmental quotient (DQ) was significantly lower
      than the other groups. The same occurred in DDST, with group I presenting
      significantly more failures than group II. Nineteen HIV children of group I had
      brain computed tomographic scan, with abnormalities in three of them (basal
      ganglia calcification, white matter hypodensity and asymmetry of lateral
      ventricles). We conclude that in HIV infected children a neurodevelopment delay
      occur early in the disease, and it can be detected by screening tests.

PMID- 11593267
TI  - Ocular cysticercosis: an epidemiological study.
AB  - The objective of the research was to verify the incidence of the ocular form of
      cysticercosis among the patients who consulted professionals of the field, during
      the first statistic inventory accomplished in the State of Parana, Brazil. The
      1996 research was performed through a questionnaire sent to all 220 members of
      Parana Ophthalmology Association and to the 17 members of Pathology and Cytology
      Department of the Parana Medical Association. A pre-stamped envelop for the
      return of the answers was included in the package. We received 99 answers from
      ophthalmologists and 10 answers from pathologists. Retrospective and
      epidemiological research about the incidences of the ocular cysticercosis in the
      State of Parana, added to national related published reports, rendered 95 cases
      probably acquired in Parana, 71 of the cases were referred in this research and
      24 in prior publication. The most frequent localization was vitreous and
      subretinal, as literature had already pointed out.

PMID- 11593268
TI  - Evaluation of headache intensity in migrainous patients with visual handicap
      through the tactile analogical scale (TAS).
AB  - The tactile analogue scale (TAS) was elaborated to be used in blind subjects or
      those who can not use the vision during their crises. The objective of this study
      was to characterize, from TAS, the architecture of migraine attacks in subjects
      with visual disability. For that, 11 migrainous with visual disturb (MVD)
      subjects were studied and 22 migrainous subjects with no visual disability as a
      control group. All patients fulfilled the criteria for migraine and the patients
      of the group studied showed visual acuteness less than 20/200. To evaluate the
      results, the patients of the group MVD were subdivide within two groups,
      according to their visual acuteness: subgroup A subjects with subnormal vision
      and subgroup B amaurotic ones. In subgroup A measurement 46 attacks with average
      of the migraine attacks of the 56.50 mm, in the subgroup B 45 attacks with
      average of the 59.58 mm and in the control group 92 attacks with average of the
      49.88 mm. When subgroup B and control group were compared there was a significant
      statistic difference (p=0.022). Through these outcomes we can observe that the
      migrainous subjects with no visual afference show a higher pain intensity during
      the migraine crises comparing to those subjects with no visual handicap. The
      study suggests that, as in other forms of sensibility, the total visual loss can
      also interfere in the nociceptive control of the pain during the migraine
      attacks.

PMID- 11593269
TI  - Dexamethasone decreases migraine recurrence observed after treatment with a
      triptan combined with a nonsteroidal anti-inflammatory drug.
AB  - BACKGROUND AND OBJECTIVES: Triptans are effective drugs for the acute treatment
      of migraine. However, 30-40% of the patients commonly present recurrence before
      24 hours therefore requiring another dose. Nonsteroidal anti-inflammatory drugs
      (NSAID) such as tolfenamic acid and naproxen sodium combined with sumatriptan
      have demonstrated efficacy in reducing recurrence observed with the single use of
      this drug. Steroids also have been suggested to treat refractory migraine and
      status migranosus. The aim of this study was to evaluate whether patients
      presenting frequent recurrence with the combination triptan plus NSAID, would
      decrease it with the association of dexamethasone. METHOD: Twenty three patients,
      17 women and 6 men with migraine according to IHS criteria were prospectively
      studied. All patients presented frequent recurrence (> or= 60%, mean recurrence
      rate 74,8%) with the single use of sumatritpan 100 mg or zolmitriptan 2,5 mg or
      rizatriptan 10mg in at least 5 consecutive attacks, and didn't present a
      reduction of the recurrence rate superior than 20% with the combination of
      tolfenamic acid 200 mg or rofecoxib 25 mg in at least 5 other consecutive attacks
      (mean recurrence rate 60%). The patients had to treat 6 consecutive moderate or
      severe migraine attacks with their usual combination plus 4 mg of dexamathasone
      with a maximum of twice a week, and fill out a diary reporting headache
      parameters. RESULTS: Twenty patients, 16 women and 4 men completed the study. Of
      those who completed the study, 11 took rizatriptan plus rofecoxib, 4 rizatriptan
      plus tolfenamic acid, 3 zolmitriptan plus rofecoxib, 1 zolmitriptan plus
      tolfenamic acid and 1 patient took sumatriptan plus tolfenamic acid, having the
      20 patients taken as a third medication, a single tablet of 4 mg of
      dexamethasone. All patients took oral formulations and none presented vomiting
      after that. Among all 20 patients, one female and one male patient presented
      recurrence in 3 out of the 6 attacks (50%) while the remaining 18 patients
      revealed recurrence in 1 or 2 treated attacks (mean 23,4%) (p<0,001). CONCLUSION:
      We concluded that the judicious use of oral dexamethasone might be useful for a
      limited population of migraine patients still presenting recurrence with the
      combination of a triptan and a NSAID. Case-control studies and studies with a
      randomized double-blind design are necessary to confirm these observations.

PMID- 11593270
TI  - Knowledge and attitudes toward epilepsy among primary, secondary and tertiary
      level teachers.
AB  - The attitudes toward people with epilepsy are influenced by the degree of
      knowledge of the condition. Teachers usually do not receive any formal
      instruction on epilepsy during their training. This study was done to access
      three hundred teachers' knowledge and attitudes toward epilepsy by answering a
      questionnaire in order to quantify their knowledge, attitude and practice toward
      epilepsy. Almost all the teachers had heard about epilepsy yet could not
      demonstrate discrimination among the students. Some teachers still thought that
      epilepsy was contagious. A few others either objected to having epileptic
      children in their classes or did not think that an epileptic child could achieve
      higher studies. The knowledge about the clinical characteristics and initial
      procedures to attend a person during a seizure was unsatisfactory. We conclude
      that schools should offer some kind of knowledge or assistance in health services
      and physicians must ensure that these teachers have sufficient knowledge of
      epilepsy. Also general public education campaigns should be encouraged in this
      field.

PMID- 11593271
TI  - Seizure's outcome after cortical resections including the face and tongue
      rolandic areas in patients with refractory epilepsy and normal MRI submitted to
      subdural grids' implantation.
AB  - PURPOSE: To study the seizure's outcome in patients with refractory epilepsy and
      normal MRI submitted to resections including the rolandic cortex. METHODS: Four
      adult patients were studied. All patients had motor or somatosensory simple
      partial seizures and normal MRI and were submitted to subdural grids'
      implantation with extensive coverage of the cortical convexity (1 in the non
      dominant and 3 in the dominant hemisphere). RESULTS: ECoG was able to define
      focal areas of seizures' onset in every patient. All patients were submitted to
      resection of the face and tongue motor and sensitive cortex; two patients had
      resections including the perirolandic cortex and 2 had additional cortical
      removals. Three patients are seizures' free and one had a greater then 90%
      reduction in seizure frequency. CONCLUSION: Resections including the face and
      tongue rolandic cortex can be safely performed even within the dominant
      hemisphere.

PMID- 11593272
TI  - The G209A mutation in the alpha-synuclein gene in Brazilian families with
      Parkinson's disease.
AB  - A missense G209A mutation of the alpha-synuclein gene was recently described in a
      large Contursi kindred with Parkinson's disease (PD). The objective of this study
      is to determine if the mutation G209A of the alpha-synuclein gene was present in
      10 Brazilian families with PD. PD patients were recruited from movement disorders
      clinics of Brazil. A family history with two or more affected in relatives was
      the inclusion criterion for this study. The alpha-synuclein G209A mutation assay
      was made using polymerase chain reaction and the restriction enzyme Tsp45I. Ten
      patients from 10 unrelated families were studied. The mean age of PD onset was
      42.7 years old. We did not find the G209A mutation in our 10 families with PD.
      Our results suggest that alpha-synuclein mutation G209A is uncommon in Brazilian
      PD families.

PMID- 11593273
TI  - Tics and Tourette syndrome: clinical evaluation of 44 cases.
AB  - We evaluated 44 patients with tics and Tourette's syndrome (TS) emphasising the
      age of onset of symptoms, sex, classification and localization of tics,
      associated symptoms and signs and comorbidities. Thirty-three patients (75.2%)
      had TS defined criteria whereas 10 (22.7%) had chronic motor and/or vocal tics.
      Simple motor tics were found in 43 cases (97.7%), mainly affecting the eyes
      (43.2%), mouth (43.2%), face (34.1%). Simple vocal tics occurred in 33 (75%).
      Coprolalia was found in just 6 cases (13.6%) and copropraxia in just 2 (4.5%).
      Obsessive compulsive disorder and/or symptoms were found in 26 cases (59.1%) and
      attention deficit in 17 (38.6%). Eighteen patients (40.9%) had other disorders,
      such as alcoholism, tabagism, drug abuse, affective disorders, anxiety, sleep and
      learning disorders. The data obtained are similar to those found by other
      authors. We highlight the low frequency of coprolalia, as well as the associated
      neuropsychiatric disorders.

PMID- 11593274
TI  - [Gilles de la Tourette syndrome: a clinical study on 58 cases].
AB  - Gilles de la Tourette's syndrome (GTS) is a neuropsychiatric disorder with a
      childhood onset and is characterized by motor and vocal tics. Fifty-eight
      patients with GTS were evaluated during a period of three years. Thirty-six
      patients were male and twenty two female, with an age range of 7 to 51 years
      (mean 20.33 years). The male to female ratio was 1.6:1. The age of onset ranged
      from 3 to 15 years (mean 7.81 years). Seventy nine percent of the patients
      presented motor tics as the initial symptom of the disease. In terms of complex
      tics, coprolalia was present in 27.6% of the patients; copropraxia in 20.1%;
      palilalia in 20.1%; ecolalia in 27.6%; and ecopraxia in 27,6%. Associated
      manifestations, such as attention deficit, hyperactivity disorder and obsessive
      compulsive disorder were present in 25.8% and 39.6%, respectively. Sensory
      phenomena were present in 54.8% of the patients.

PMID- 11593275
TI  - [Idiopathic facial paralysis (Bell's palsy): a study of 180 patients].
AB  - The objective of this study was to analyze some clinical and epidemiologic
      aspects, as well as the follow up of 180 patients with Bell's palsy. In the study
      population there was a predominance of female (66.7%). Two peaks of incidence in
      the age distribution were identified: third-fourth and sixth decades of life. In
      the group of 180 patients there were 198 events of facial paralysis, 17
      recurrences and in one patient the paralysis was bilateral at the onset. In 15
      patients (8.3%) there were recurrences of the facial paralysis, in 12 cases
      (70.6%) the recurrences were ipsilateral. The left side of the face was involved
      in 55.6% of the cases. In eight patients the paralysis occurred during pregnancy
      (n=5) or puerperium (n=3). As associated conditions we found: arterial
      hypertension (11.7%), diabetes mellitus (11.1%), pregnancy or puerperium (4.4%;
      6.7% in the women), and neurocysticercosis (1.1%). In 72.8% of the cases no
      association with such conditions was found. In 22.8% of the patients some kind of
      sequelae were identified: hemifacial spasm (12.8%), partial recovery of the motor
      deficit (10.6%), syndrome of the crocodile tears (3.3%), sincinetic contraction
      (2.8%), and the Marcus Gunn inverse phenomenon (1.1%). In conclusion, this study
      shows that the idiopathic facial paralysis may lead to important sequelae in more
      than 20% of the patients.

PMID- 11593276
TI  - [Stroke in young adults: analysis of 164 patients].
AB  - We retrospectively analyzed the epidemiological features of 164 out-clinic
      patients with a first-onset stroke between 15 and 49 years old. Ischemic stroke
      occurred in 141 patients, hemorrhagic stroke in 16 patients, and venous
      thrombosis in 7 patients. Forty-eight percent of ischemic strokes were
      atherothrombotic, but no etiology was found in 32% of patients with ischemic
      stroke. Systemic arterial hypertension was the most frequent etiology in the
      hemorrhagic stroke group. The most frequent risk factors were systemic arterial
      hypertension, smoking, hypercholesterolemia, alcoholism and diabetes mellitus.
      Although stroke in young adults deserves some specific etiological investigation,
      we found that ordinary risk factors such as hypertension, tobacco use,
      hypercholesteremia and diabetes were prevalent in our population. It seems that
      prevention campaigns should be the target of our work.

PMID- 11593277
TI  - [Meningiomas of the cavernous sinus: the surgical resectability and
      complications].
AB  - The optimal management for patients with cavernous sinus meningiomas is to
      evacuate tumor without causing mortality or morbidity. The records of 16
      patients, including 11 women and 5 men ranging in age from 31 to 63 years,
      underwent surgical treatment for this condition were reviewed. Completeness of
      tumor resection, cranial nerve morbidity, complications, mortality, the internal
      carotid artery encasement and outcome were studied. Total removal was achieved in
      six patients. Of ten patients who underwent subtotal resection there was one
      death and four were sent to radiotherapy. Morbidity was 24% for cranial nerves
      controlling extraocular motor function; trigeminal nerve function did not improve
      after surgical treatment. Symptomatic recurrence occurred in two patients who
      underwent subtotal tumor resection and in one who underwent complete tumor
      resection. The average follow-up period was of 26 months. According to our
      findings, we conclude: 1) the resectability of meningiomas of cavernous sinus
      depends on the degree of internal carotid artery involvement; 2) total resection
      of meningiomas confined in cavernous sinus is rare; 3) morbidity of the cranial
      nerves is significant; 4) subtotal resection is an effective mean to obtain
      control of the disease.

PMID- 11593278
TI  - [Subcortical hyperintensities on magnetic resonance imaging: a comparison of
      normal and depressed elderly subjects].
AB  - Previous studies reported that depressed subjects had more signal
      hyperintensities on magnetic resonance imaging scans than control subjects, but
      the subjects had cerebrovascular disease risk factors. This study used subjects
      with a history of major depression and matched comparison subjects, screened to
      exclude cerebrovascular risk factors, to determine whether depressed subjects had
      more white matter hyperintensities and other lesions. We evaluated the prevalence
      and severity of MRI signal hyperintensities in 30 elderly depressed patients and
      20 controls matched for age. Deep matter hyperintensities, periventricular
      hyperintensities and subcortical gray hyperintensities were rated on a standard 0
      3 scale by two radiologists blind to clinical diagnosis. No significant
      differences were found between groups for the presence of subcortical gray
      matter, deep white matter and periventricular hyperintensities. These findings
      suggest that cerebrovascular disease risk factors most likely mediated the
      relationship between depression and hyperintensities in previous studies.

PMID- 11593279
TI  - [Correlation between diagnostic hypothesis and result of cranial computed axial
      tomography].
AB  - The use of computed axial tomography (CT) in the investigation of neurologic
      disorders is attractive for its disponibility in the health services. However,
      the indications of the exam and the correlation with the clinical features has
      not been frequently studied. We study correlation between the requests of CT and
      the findings reported by the radiologist, in 367 exams performed from 07/1995 to
      07/ 1996. The mean age was 31.7 +/- 22.9 years. The CT were requested in
      decrescent order of frequency by the Services of Neurology (36.2%), Emergency
      room (17.4%), Pediatric Neurology (16.9%) and Internal Medicine (5.9%). The CT
      was more indicated in cases of seizures (30%), headache (26.2%), motor impairment
      (20.2%) and reduction of conscience level (16.9%). The main hypothetic diagnosis
      were "to discard anatomic lesions" (9.0%), not specified stroke (8.2%) and
      neurocisticercosis (8.2%). The result of the CT was normal in 50.4% of the exams
      specially those requested in cases of headache (94.4%), seizures (71.4%) and "to
      discard anatomic lesions"(66.7%). The more frequently CT abnormalities were
      hydrocephalus (5.4%), ischemic stroke (5.4%) and neoplasm (3.5%) The greatest
      rates of correlation were among those to discard anatomic lesions (66,7%),
      hydrocephalus (50%), ischemic stroke (50%) and hematoma (50%). We concluded that
      CT is more helpful if more clinical data is provided in the request form, so
      aiding the radiologist in the final report.

PMID- 11593280
TI  - [Topiramate: an experience in children with partial epilepsy].
AB  - Topiramate (TPM) is a new drug currently used in Brazil. We verified the clinical
      responses to TPM in children under 15 years-old. We started with 12.5 mg/day (1-7
      mg/kg/day) and the doses increased 12,5 mg each week. Eleven children were
      studied, 9 females and 2 males, from 3 to 14 years-old with partial epilepsy
      associated to different etiological factors. Only one patient had an intense
      abdominal pain. The patients had weekly or daily seizures and after began TPM 1
      patient stayed free from seizures, 5 improved more than 75% in frequency, 1
      patient improved more than 50% and 3 had no control. A good control of seizures
      was achieved with a low dose of TPM as monotherapy and add-on therapy with
      carbamazepine even in severe cases.

PMID- 11593281
TI  - [Clinical profile and criteria for the diagnosis of schistosomal
      myeloradiculopathy].
AB  - During 20 year period (1972-1992) 56 patients with a diagnosis of schistosomal
      myeloradiculopathy were admitted in three hospitals of Belo Horizonte-Minas
      Gerais. Data from patients were collected retrospectively from their medical
      records. In all cases, the diagnosis was inferred in a presumably way and was
      based on the following considerations: 1) the finding of low thoracic/upper
      lumbar neurological symptoms; 2) positive epidemiology for schistosomiasis; 3)
      demonstration of exposure to schistosomiasis through parasitologic or serologic
      techniques; and 4) the exclusion of other known causes of transverse myelitis and
      myeloradiculitis. Several clinical and epidemiological aspects were studied to
      determine the diagnosis profiles of the schistosomal myeloradiculopathy in this
      sample and are presented in this paper. In recognizing the many problems in
      diagnosis of schistosomal myeloradiculopathy we emphasize how important is
      thinking about this entity and criteria to improve diagnostic evaluation are
      suggested.

PMID- 11593282
TI  - [Cerebrovascular disease and neurocysticercosis].
AB  - We report three cases of stroke secondary to neurocysticercosis. The first one is
      a 36 years old man with bilateral middle cerebral artery occlusions who had
      presented acute right hemiparesia and aphasia. MRI demonstrated several enhancing
      subarachnoid cysts surrounding the occluded vessels, a right parietal racemose
      cyst and a left temporal large infarction area. Angiographic study showed total
      occlusion of left middle cerebral artery and a subtotal occlusion of right middle
      cerebral artery. The second one is a 42 years old man with vasculitis of small
      cortical vessels who presented with headache, seizures and focal neurological
      deficit. CT scan demonstrated several calcifications and a left temporal
      infarction area. Cerebral angiographic study was normal. The third case was a
      woman, 53 years old, with a past history of six stroke events and an actual
      behavior disturbance and seizures. MRI demonstrated several cortical and
      subcortical infarction areas and cisternal cysts. Angiographic study showed
      diffuse arteritis of basilar and carotid arterial system. In all three cases CSF
      study showed linfomonocitic pleocytosis and positive ELISA for cysticercosis.

PMID- 11593283
TI  - Reversible posterior leucoencephalopathy syndrome associated with bone marrow
      transplantation.
AB  - Reversible posterior leucoencephalopathy syndrome (RPLS) has previously been
      described in patients who have renal insufficiency, eclampsia, hypertensive
      encephalopathy and patients receiving immunosuppressive therapy. The mechanism by
      which immunosuppressive agents can cause this syndrome is not clear, but it is
      probably related with cytotoxic effects of these agents on the vascular
      endothelium. We report eight patients who received cyclosporine A (CSA) after
      allogeneic bone marrow transplantation or as treatment for severe aplastic anemia
      (SSA) who developed posterior leucoencephalopathy. The most common signs and
      symptoms were seizures and headache. Neurological dysfunction occurred preceded
      by or concomitant with high blood pressure and some degree of acute renal failure
      in six patients. Computerized tomography studies showed low-density white matter
      lesions involving the posterior areas of cerebral hemispheres. Symptoms and
      neuroimaging abnormalities were reversible and improvement occurred in all
      patients when given lower doses of CSA or when the drug was withdrawn. RPLS may
      be considered an expression of CSA neurotoxicity.

PMID- 11593284
TI  - Hereditary spastic paraplegia associated with thin corpus callosum.
AB  - Autosomal recessive hereditary spastic paraplegia (AR-HSP) associated with thin
      corpus callosum was recently described in Japan, and most families were linked to
      chromosome 15 q13-15. We report two patients from two different Brazilian
      families with progressive gait disturbance starting at the second decade of life,
      spastic paraparesis, and mental deterioration. One patient presented cerebellar
      ataxia. Magnetic resonance imaging (MRI) of the head of both patients showed a
      thin corpus callosum. AR-HSP with a thin corpus callosum is a rare disorder,
      mainly described in Japanese patients. We found only 4 Caucasian families with AR
      HSP with thin corpus callosum described in the literature. Further studies
      including additional Caucasian families of AR-HSP with thin corpus callosum are
      required to delineate the genetic profile of this syndrome in occidental
      countries.

PMID- 11593285
TI  - Hemorrhage in cerebral metastasis from angiosarcoma of the heart: case report.
AB  - The purpose of this article is to describe the clinical and pathological features
      of metastatic angiosarcoma in the central nervous system. Only a few cases of
      cerebral metastasis from angiosarcoma of the heart have been recorded in the
      literature; particularly related to intracerebral hemorrhage. A case of secondary
      cerebral angiosarcoma of the heart in a 33 years old man is presented. The
      initial symptoms were headache, vomiting, lethargy and aphasia. There was a mass
      in the left temporal lobe with hemorrhage and edema on the computerized
      tomography (CT). After 24 hours the neurological status worsened and another CT
      scan showed rebleeding on the tumor area. He underwent an emergency craniotomy
      but died two days after. Considering the longer survival of sarcoma patients with
      new modalities of treatment, the incidence of brain metastasis may increase,
      demanding a better preventive and more aggressive approach. Besides, due to the
      hemorrhagic nature of such lesions, we suggest the immediate surgery to prevent a
      fast and lethal evolution because rebleeding.

PMID- 11593286
TI  - Reversal of severe SPECT asymmetry after venous extra-intracranial high flow
      bypass in a patient submitted to therapeutic internal carotid occlusion: case
      report.
AB  - Therapeutic occlusion of the internal carotid artery is the main option for the
      treatment of the symptomatic intracavernous internal carotid artery aneurysms,
      but the issue of the best way of doing the balloon test occlusion (BTO) regarding
      prediction of future ischemic events remains debatable. Single photon emission
      computerized tomography (SPECT) has been offered as one of the best option of
      monitoring regional cerebral blood flow (rCBF) during the BTO, where severe
      asymmetry is predictive of delayed ischemia. We describe a case of important
      SPECT asymmetry during BTO clinically negative and its complete reversal with
      carotid occlusion after extra-intracranial bypass with high flow safenous vein
      bypass between the cervical carotid artery and the middle cerebral artery.

PMID- 11593287
TI  - Complete remission of epileptic psychosis after temporal lobectomy: case report.
AB  - We report a case of a female patient with refractory complex partial seizures
      since 15 years of age, recurrent postictal psychotic episodes since 35 which
      evolved to a chronic refractory interictal psychosis and MRI with right mesial
      temporal sclerosis (MTS). After a comprehensive investigation (video-EEG
      intensive monitoring, interictal and ictal SPECT, and a neuropsychological
      evaluation including WADA test) she was submitted to a right temporal lobectomy.
      Since then, she has been seizure-free with remission of psychosis, although with
      some persistence of personality traits (hiperreligiosity, viscosity) which had
      been present before surgery. This case supports the idea that temporal lobectomy
      can be a safe and effective therapeutic measure for patients with MTS, refractory
      epilepsy and recurrent postictal epileptic psychosis or interictal epileptic
      psychosis with postictal exacerbation.

PMID- 11593288
TI  - Orbital apex syndrome due to aspergillosis: case report.
AB  - We report the case of a 73-year-old female who presented facial numbness and pain
      in the first division of the trigeminal nerve, ptosis, diplopia and visual loss
      on the right side for the previous four months. The neurological, radiological
      and histological examination demonstrated a rare case of invasive fungal
      aspergillosis of the central nervous system, causing orbital apex syndrome, later
      transformed in temporal brain abscess. She died ten months later due to
      respiratory and renal failure in spite of specific antimycotic therapy.

PMID- 11593289
TI  - Machado-Joseph disease versus hereditary spastic paraplegia: case report.
AB  - Machado-Joseph disease (MJD) is the most common autosomal dominant
      spinocerebellar ataxia and presents great phenotypic variability. MJD presenting
      with spastic paraparesis was recently described in Japanese patients. We report
      the case of 41-year-old woman with the phenotype of complicated hereditary
      spastic paraplegia. Her father died at the age of 56 years due to an undiagnosed
      progressive neurological disease that presented parkinsonism. She had an expanded
      allele with 66 CAG repeats and a normal allele with 22 repeats in the gene of
      MJD. MJD should be considered in the differential diagnosis of autosomal dominant
      complicated HSP. A patient with the phenotype of complicated HSP and relatives
      with other clinical features of a neurodegenerative disease should raise the
      suspicion of MJD.

PMID- 11593290
TI  - [Moebius syndrome: case report].
AB  - In the last few years we have been able to diagnose a larger number of cases of
      Moebius syndrome, perhaps due to its increased incidence--since a number of
      environmental factors have been related to the genesis of the syndrome. Out of
      the cases evaluated in two specialized ambulatory, it is worthwhile to mention
      one of them due to an uncommon association with cortical heterotopy, among others
      malformations.

PMID- 11593291
TI  - [Cerebral venous thrombosis and homocystinuria: case report].
AB  - Homocystinuria presenting as cerebral venous thrombosis is not usual. We report
      on a 13-year-old boy who was admitted to the hospital due to severe headache,
      nausea, vomiting and fever (38 degrees C). The patient was Marfan like and
      presented left hemiparesis and meningeal irritation sings. He was mentally
      retarded, had severe myopia, and had right lens dislocation one month before.
      Cranial CT scan was suggestive of cerebral venous infarct. MRI and magnetic
      resonance angiography showed venous infarcts more prominent in the right thalamic
      projection with hemorrhagic transformation and multiple foci of cortical
      (occipital and parietal bilaterally) deep parietal and left capsular bleeding,
      secondary of thrombosis of the transverse and sigmoid venous sinuses. High levels
      of homocysteine were detected in the blood and urine. Homocystinuria is an
      autosomal recessive inborn error of methionine metabolism caused by cystathionine
      beta-synthase defect in most cases. We discuss the clinical and radiological
      findings in this patient, analyzing the pathophysiology of the thrombotic events
      related to homocystinuria.

PMID- 11593292
TI  - [Occult intrasacral meningocele: case report].
AB  - Intrasacral meningoceles are rare conditions that can cause symptoms of nerve
      root compression. We report a case of a 18-year-old female, who presented with
      urinary incontinence. The neurological and urological evaluation revealed lack of
      detrusor muscle reflex. This finding supported the hypothesis of spinal
      disraphism. Magnetic resonance image revealed an intrasacral meningocele. The
      patient was submitted to surgical excision of the lesion without postoperative
      complications. In the present paper, the pathogenesis, clinical picture,
      neuroradiological findings and surgical treatment are discussed.

PMID- 11593293
TI  - [Fatal necro-hemorrhagic pancreatitis related to sodium valproate: case report].
AB  - Among the idiosyncratic reactions related to VPA, pancreatitis is the most rare
      and less remembered even though its potentially fatal course. We report the case
      of a 5 year-old boy with epilepsy treated with VPA 40 mg/kg/day associated with
      CBZ 20 mg/kg/day and PB 3 mg/kg/day, admitted for vomiting, abdominal pain, low
      grade fever, abdominal tension and amylasis of 288 UI. On evolution presented
      upper digestive hemorrhage, shock and amylasis of 564 UI. The patient was
      submitted to exploratory laparotomy with findings of hemorrhagic ascitis,
      retroperitoneal hematoma, increased volume of pancreas with edema and hemorrhage
      leading to diagnosis of necro-hemorrhagic pancreatitis and a fatal course.
      Pancreatic complications are well known complications related to VPA treatment
      and may vary between asymptomatic hyperamilasemy to fatal acute pancreatitis. The
      characteristics of our patient correlates with the data on literature: we found 7
      similar cases reported, 4 of which died.

PMID- 11593294
TI  - [Cerebellar abscess treated by clinical management: case report].
AB  - We report a case of cerebellar abscess secondary to chronic otitis and localized
      in the right cerebellar hemisphere, in a pediatric patient. The abscess was
      treated only by antibiotic therapy, evolving to complete clinical and
      radiological resolution, without neurosurgical intervention. We also discuss the
      pathogenesis, histopathogenesis, clinical manifestations and the forms of
      treatment of CNS abscesses.

PMID- 11593295
TI  - [Laryngeal dystonia].

PMID- 11593296
TI  - Preeclampsia: from epidemiological observations to molecular mechanisms.
AB  - Preeclampsia is the main cause of maternal mortality and is associated with a
      five-fold increase in perinatal mortality in developing countries. In spite of
      this, the etiology of preeclampsia is unknown. The present article analyzes the
      contradictory results of the use of calcium supplementation in the prevention of
      preeclampsia, and tries to give an explanation of these results. The proposal of
      an integrative model to explain the clinical manifestations of preeclampsia is
      discussed. In this proposal we suggest that preeclampsia is caused by
      nutritional, environmental and genetic factors that lead to the creation of an
      imbalance between the free radicals nitric oxide, superoxide and peroxynitrate in
      the vascular endothelium. The adequate interpretation of this model would allow
      us to understand that the best way of preventing preeclampsia is the
      establishment of an adequate prenatal control system involving adequate
      antioxidant vitamin and mineral supplementation, adequate diagnosis and early
      treatment of asymptomatic urinary and vaginal infections. The role of infection
      in the genesis of preeclampsia needs to be studied in depth because it may
      involve a fundamental change in the prevention and treatment of preeclampsia.

PMID- 11593297
TI  - Molecular characterization of DDX26, a human DEAD-box RNA helicase, located on
      chromosome 7p12.
AB  - DEAD-box proteins comprise a family of ATP-dependent RNA helicases involved in
      several aspects of RNA metabolism. Here we report the characterization of the
      human DEAD-box RNA helicase DDX26. The gene is composed of 14 exons distributed
      over an extension of 8,123 bp of genomic sequence and encodes a transcript of 1.8
      kb that is expressed in all tissues evaluated. The predicted amino acid sequence
      shows a high similarity to a yeast DEAD-box RNA helicase (Dbp9b) involved in
      ribosome biogenesis. The new helicase maps to 7p12, a region of frequent
      chromosome amplifications in glioblastomas involving the epidermal growth factor
      receptor (EGFR) gene. Nevertheless, co-amplification of DDX26 with EGFR was not
      detected in nine tumors analyzed.

PMID- 11593298
TI  - Ectonucleotidase activities in Sertoli cells from immature rats.
AB  - Sertoli cells have been shown to be targets for extracellular purines such as ATP
      and adenosine. These purines evoke responses in Sertoli cells through two
      subtypes of purinoreceptors, P2Y2 and P A1. The signals to purinoreceptors are
      usually terminated by the action of ectonucleotidases. To demonstrate these
      enzymatic activities, we cultured rat Sertoli cells for four days and then used
      them for different assays. ATP, ADP and AMP hydrolysis was estimated by measuring
      the Pi released using a colorimetric method. Adenosine deaminase activity (EC
      3.5.4.4) was determined by HPLC. The cells were not disrupted after 40 min of
      incubation and the enzymatic activities were considered to be ectocellularly
      localized. ATP and ADP hydrolysis was markedly increased by the addition of
      divalent cations to the reaction medium. A competition plot demonstrated that
      only one enzymatic site is responsible for the hydrolysis of ATP and ADP. This
      result indicates that the enzyme that acts on the degradation of tri- and
      diphosphate nucleosides on the surface of Sertoli cells is a true ATP
      diphosphohydrolase (EC 3.6.1.5) (specific activities of 113 +/- 6 and 21 +/- 2
      nmol Pi mg(-1) min(-1) for ATP and ADP, respectively). The ecto-5'-nucleotidase
      (EC 3.1.3.5) and ectoadenosine deaminase activities (specific activities of 32 +/
      2 nmol Pi mg(-1) min(-1) for AMP and 1.52 +/- 0.13 nmol adenosine mg(-1) min(
      1), respectively) were shown to be able to terminate the effects of purines and
      may be relevant for the physiological control of extracellular levels of
      nucleotides and nucleosides inside the seminiferous tubules.

PMID- 11593299
TI  - In vitro cytotoxicity of the LDE: daunorubicin complex in acute myelogenous
      leukemia blast cells.
AB  - Acute myelogenous leukemia (AML) blast cells show high-affinity degradation of
      low-density lipoprotein (LDL), suggesting an increased expression of cellular LDL
      receptors. LDE is a lipid microemulsion easily synthesized in vitro which is
      known to mimic the metabolic pathway of LDL. We used LDE as a carrier for
      daunorubicin and assayed the cytotoxicity of the complex using AML blast cells
      since RT-PCR analysis showed that AML cells express LDL receptor mRNA. The
      LDE:daunorubicin complex killed 46.7% of blast cells and 20.2% of normal bone
      marrow cells (P<0.001; Student t-test). Moreover, this complex destroyed AML
      blast cells as efficiently as free daunorubicin. Thus, LDE might be a suitable
      carrier of chemotherapeutic agents targeting these drugs to neoplastic cells and
      protecting normal tissues.

PMID- 11593300
TI  - In vivo and in vitro effect of imipramine and fluoxetine on Na+,K+-ATPase
      activity in synaptic plasma membranes from the cerebral cortex of rats.
AB  - The effects of in vivo chronic treatment and in vitro addition of imipramine, a
      tricyclic antidepressant, or fluoxetine, a selective serotonin reuptake
      inhibitor, on the cortical membrane-bound Na+,K+-ATPase activity were studied.
      Adult Wistar rats received daily intraperitoneal injections of 10 mg/kg of
      imipramine or fluoxetine for 14 days. Twelve hours after the last injection rats
      were decapitated and synaptic plasma membranes (SPM) from cerebral cortex were
      prepared to determine Na+,K+-ATPase activity. There was a significant decrease
      (10%) in enzyme activity after imipramine but fluoxetine treatment caused a
      significant increase (27%) in Na+,K+-ATPase activity compared to control (P<0.05,
      ANOVA; N = 7 for each group). When assayed in vitro, the addition of both drugs
      to SPM of naive rats caused a dose-dependent decrease in enzyme activity, with
      the maximal inhibition (60-80%) occurring at 0.5 mM. We suggest that a)
      imipramine might decrease Na+,K+-ATPase activity by altering membrane fluidity,
      as previously proposed, and b) stimulation of this enzyme might contribute to the
      therapeutic efficacy of fluoxetine, since brain Na+,K+-ATPase activity is
      decreased in bipolar patients.

PMID- 11593301
TI  - Comparison of the quantitative competitive and semiquantitative RT-PCR methods
      for the determination of interferon-gamma mRNA levels in AIDS-free HIV-infected
      individuals.
AB  - IFN-gamma mRNA expression was evaluated in nonstimulated peripheral blood
      mononuclear cells (PBMC) of HIV-infected and seronegative individuals using
      quantitative competitive and semiquantitative RT-PCR and the sensitivity of these
      methods was compared. A significant correlation was found between quantitative
      competitive and semiquantitative RT-PCR in samples of both HIV-seronegative (P =
      0.004) and HIV-infected individuals (P = 0.0004). PBMC from HIV-infected
      individuals presented a remarkable increase of IFN-gamma mRNA expression, as
      determined by both types of RT-PCR methods. Semiquantitative RT-PCR even without
      an internal standard is also acceptable for measuring cytokine mRNA expression,
      but less reliable if small amounts are quantified. Moreover, we found that
      increased IFN-gamma mRNA expression is independent of CD4+ cell count in AIDS
      free HIV-infected patients.

PMID- 11593302
TI  - Obese women on a low energy rice and bean diet: effects of leucine, arginine or
      glycine supplementation on protein turnover.
AB  - This study examined if leucine, arginine or glycine supplementation in adult
      obese patients (body mass index of 33 +/- 4 kg/m(2)) consuming a Brazilian low
      energy and protein diet (4.2 MJ/day and 0.6 g protein/kg) affects protein and
      amino acid metabolism. After four weeks adaptation to this diet, each subject
      received supplements of these amino acids (equivalent to 0.2 g protein kg(-1)
      day(-1)) in random order. On the seventh day of each amino acid supplementation,
      a single-dose 15N-glycine study was carried out. There were no significant
      differences in protein flux, synthesis or breakdown. The protein flux (grams of
      nitrogen, gN/9 h) was 55 +/- 24 during the nonsupplemented diet intake and 39 +/-
      10, 44 +/- 22 and 58 +/- 35 during the leucine-, glycine- and arginine
      supplemented diet intake, respectively; protein synthesis (gN/9 h) was 57 +/- 24,
      36 +/- 10, 41 +/- 22 and 56 +/- 36, respectively; protein breakdown (gN/9 h) was
      51 +/- 24, 34 +/- 10, 32 +/- 28 and 53 +/- 35, respectively; kinetic balance
      (gN/9 h) was 3.2 +/- 1.8, 4.1 +/- 1.7, 3.4 +/- 2.9 and 3.9 +/- 1.6. There was no
      difference in amino acid profiles due to leucine, arginine or glycine
      supplementation. The present results suggest that 0.6 g/kg of dietary protein is
      enough to maintain protein turnover in obese women consuming a reduced energy
      diet and that leucine, arginine or glycine supplementation does not change
      kinetic balance or protein synthesis.

PMID- 11593303
TI  - Ambulatory blood pressure and Doppler echocardiographic indexes of borderline
      hypertensive men presenting an exaggerated blood pressure response during dynamic
      exercise.
AB  - Borderline hypertension (BH) has been associated with an exaggerated blood
      pressure (BP) response during laboratory stressors. However, the incidence of
      target organ damage in this condition and its relation to BP hyperreactivity is
      an unsettled issue. Thus, we assessed the Doppler echocardiographic profile of a
      group of BH men (N = 36) according to office BP measurements with exaggerated BP
      in the cycloergometric test. A group of normotensive men (NT, N = 36) with a
      normal BP response during the cycloergometric test was used as control. To assess
      vascular function and reactivity, all subjects were submitted to the cold pressor
      test. Before Doppler echocardiography, the BP profile of all subjects was
      evaluated by 24-h ambulatory BP monitoring. All subjects from the NT group
      presented normal monitored levels of BP. In contrast, 19 subjects from the
      original BH group presented normal monitored BP levels and 17 presented elevated
      monitored BP levels. In the NT group all Doppler echocardiographic indexes were
      normal. All subjects from the original BH group presented normal left ventricular
      mass and geometrical pattern. However, in the subjects with elevated monitored BP
      levels, fractional shortening was greater, isovolumetric relaxation time longer,
      and early to late flow velocity ratio was reduced in relation to subjects from
      the original BH group with normal monitored BP levels (P<0.05). These subjects
      also presented an exaggerated BP response during the cold pressor test. These
      results support the notion of an integrated pattern of cardiac and vascular
      adaptation during the development of hypertension.

PMID- 11593304
TI  - The cognitive subscale of the "Alzheimer's Disease Assessment Scale" in a
      Brazilian sample.
AB  - The cognitive subscale of the "Alzheimer's Disease Assessment Scale" (ADAS-Cog)
      is widely used for the evaluation of dementia and is very popular in dementia
      drug trials because of the characteristics of the scale. The objective of the
      present study was to adapt the ADAS-Cog for use for the Brazilian population. A
      major problem is that education is variable, a fact that may influence
      performance in cognitive evaluation. This study was conducted on a control group
      (CG) of 96 subjects (25 males and 71 females aged 68 +/- 8.6 years) and on 44
      Alzheimer's disease (AD) patients (19 males and 25 females aged 72 +/- 6.4 years)
      with mild dementia (Clinical Dementia Rating score 1). For statistical analysis
      groups were divided into three educational levels: I, 0-4 years of schooling (65
      CG/20 AD); II, 5-11 years of schooling (19 CG/7 AD), and III, 12 or more years of
      schooling (12 CG/17 AD). The battery was applied according to original
      instructions. Total mean score for CG and AD was 10.9 and 22.9 for level I, 7.8
      and 22.4 for level II, and 6.2 and 15.4 for level III, respectively. These
      results indicate that our version of the ADAS-Cog is useful to identify mild
      dementia, though there may be an overlapping when comparing high education
      demented with low education non-demented subjects.

PMID- 11593305
TI  - Mirtazapine versus fluoxetine in the treatment of panic disorder.
AB  - Mirtazapine is an antidepressant whose side effect profile differs from that of
      first-line agents (selective serotonin reuptake inhibitors) used in the treatment
      of panic disorder. The present study compared the effect of mirtazapine and
      fluoxetine in the treatment of panic disorder in a double-blind, randomized,
      flexible-dose trial conducted with outpatients. After a 1-week single-blind
      placebo run-in, 27 patients entered an 8-week double-blind phase in which they
      were randomly assigned to treatment with either mirtazapine or fluoxetine. Both
      groups improved significantly in all but one efficacy measure (P < or = 0.01).
      ANOVA showed no significant differences between the two treatment groups in
      number of panic attacks, Hamilton Anxiety Scale or Sheehan Phobic Scale, whereas
      measures of patient global evaluation of phobic anxiety were significantly
      different between groups (F1,20 = 6.91, P = 0.016) favoring mirtazapine. For the
      22 patients who completed the study, the mean daily dose of mirtazapine was 18.3
      +/- 1.3 vs 14.0 +/- 1.0 mg for fluoxetine at the endpoint. Weight gain occurred
      more frequently in the mirtazapine group (50 vs 7.7%, P = 0.04) and nausea and
      paresthesia occurred more often in the fluoxetine group (P = 0.01). Results
      suggest that mirtazapine has properties that make it attractive for the treatment
      of panic disorder.

PMID- 11593306
TI  - Interleukin 8 as a vaso-occlusive marker in Brazilian patients with sickle cell
      disease.
AB  - Sickle cell disease has a worldwide distribution and is a public health problem
      in Brazil. Although vaso-occlusive crisis (VOC) is one of the most important
      clinical features of the disease, there are still several steps of its
      pathogenesis which are unknown. The increase of the chemotactic factor
      interleukin 8 (IL-8) has been reported to be involved in sickle cell disease
      crisis, but this has not been demonstrated conclusively. In the present study we
      analyzed serum IL-8 levels by ELISA and hematological parameters and hemoglobin
      patterns by standard techniques in 23 (21 SS and 2 SC) Brazilian patients with
      sickle cell syndromes during VOC caused by different inducing factors, 22 (21 SS
      and 1 SC) sickle cell patients out of crisis, and 11 healthy controls. Increased
      IL-8 levels were observed in 19 of 23 VOC patients (79.2%), 3 of them with more
      than 1,000 pg/ml. Seventeen of 22 (77.3%) non-crisis patients showed low IL-8
      levels (less than 15 pg/ml). Healthy controls had low IL-8 levels. A significant
      difference in serum IL-8 levels was observed between crisis and non-crisis sickle
      cell patients (P<0.0001). There was no correlation between IL-8 levels and
      hematological data or hemoglobin patterns. High serum IL-8 levels were observed
      in VOC patients independently of the crisis-inducing factor. We conclude that in
      the studied population, IL-8 concentration may be a useful VOC marker, although
      the mechanism of the pathogenic process of sickle cell VOC syndromes remains
      unclear.

PMID- 11593307
TI  - Development according to pubertal stage in Brazilian children and adolescents
      with short-term diabetes.
AB  - The anthropometric status and metabolic control of 51 recently diagnosed
      Brazilian schoolchildren with type 1 diabetes (DM1), during the first 5 years of
      the disease, were compared with those of normal children (60 girls and 132 boys)
      belonging to the same environmental condition and pubertal stage. Metabolic
      control was evaluated on the basis of fasting plasma glucose (FPG) and HbA1c
      levels. The criteria of the National Center for Health Statistics were used for
      anthropometric evaluation. FPG (205 +/- 51 mg/dl for girls vs 200 +/- 34 mg/dl
      for boys) and % above upper normal limit of median HbA1c (1.8% for girls vs 2.5%
      for boys with diabetes) were not significantly different during follow-up. The Z
      score of the last height evaluation was lower in the girls' group (-0.14 vs 
      0.53, P<0.05). By forward stepwise analysis, the Z-score of the initial height
      was statistically significant as a determinant factor for height at the end of
      the study in both girls and boys with DM1. The Z-score of weight at last
      evaluation was not different from that at diagnosis in either sex. However,
      analysis according to pubertal stage showed a tendency to a weight increase in
      the girls. The weight recovery and height loss in girls with DM1 follows the
      trend of the normal Brazilian population.

PMID- 11593308
TI  - Frequent occurrence of nicotinic acetylcholine receptors in GABAergic neurons of
      the chick visual system.
AB  - Double-labeling immunohistochemical methods were used to investigate the
      occurrence of the alpha8 and alpha5 nicotinic receptor subunits in presumptive
      GABAergic neurons of the chick nervous system. Nicotinic receptor
      immunoreactivity was often found in cells exhibiting GABA-like immunoreactivity,
      especially in the visual system. The alpha8 subunit appeared to be present in
      presumptive GABAergic cells of the ventral lateral geniculate nucleus, nucleus of
      the basal optic root of the accessory optic system, and the optic tectum, among
      several other structures. The alpha5 subunit was also found in GABA-positive
      neurons, as observed in the lentiform nucleus of the mesencephalon and other
      pretectal nuclei. The numbers of alpha8- and alpha5-positive neurons that were
      also GABA-positive represented high percentages of the total number of neurons
      containing nicotinic receptor labeling in several brain areas, which indicates
      that most of the alpha8 and alpha5 nicotinic receptor subunits are present in
      GABAergic cells. Taken together with data from other studies, our results
      indicate an important role of the nicotinic acetylcholine receptors in the
      functional organization of GABAergic circuits in the visual system.

PMID- 11593309
TI  - The effect of porphyrins on normal and transformed mouse cell lines in the
      presence of visible light.
AB  - Photodynamic therapy consists of the uptake of a photosensitizing dye, often a
      porphyrin, by tumor tissue and subsequent irradiation of the tumor with visible
      light of an appropriate wavelength matched to the absorption spectrum of the
      photosensitizing dye. This class of molecules produces reactive oxygen species
      when activated by light, resulting in a direct or indirect cytotoxic effect on
      the target cells. Photodynamic therapy has been used in the treatment of cancer
      but the technology has a potential for the treatment of several disease
      conditions mainly because of its selectivity. However, it is not clear why the
      porphyrins are retained preferentially by abnormal tissue. This paper describes a
      study of the effect of the association of porphyrin and visible light on two
      mouse fibroblast cell lines: A31, normal cells and B61, an EJ-ras transformed
      variant of A31. Two water-soluble porphyrins were used, a positively charged one,
      tetra(N-methyl-4-pyridyl)porphyrin chloride, and a negatively charged one,
      tetra(4-sulfonatophenyl)porphyrin-Na salt (TPPS4) in order to assess the effect
      on cell survival. The results suggest that the B61 cell line is more sensitive to
      incubation with the anionic porphyrin (TPPS4) followed by light irradiation and
      that the anionic porphyrin is more efficient in killing the cells than the
      cationic porphyrin.

PMID- 11593310
TI  - Effects of terpineol on the compound action potential of the rat sciatic nerve.
AB  - Terpineol, a volatile terpenoid alcohol of low toxicity, is widely used in the
      perfumery industry. It is an important chemical constituent of the essential oil
      of many plants with widespread applications in folk medicine and in aromatherapy.
      The effects of terpineol on the compound action potential (CAP) of rat sciatic
      nerve were studied. Terpineol induced a dose-dependent blockade of the CAP. At
      100 microM, terpineol had no demonstrable effect. At 300 microM terpineol, peak
      to-peak amplitude and conduction velocity of CAP were significantly reduced at
      the end of 180-min exposure of the nerve to the drug, from 3.28 +/- 0.22 mV and
      33.5 +/- 7.05 m/s, respectively, to 1.91 +/- 0.51 mV and 26.2 +/- 4.55 m/s. At
      600 microM, terpineol significantly reduced peak-to-peak amplitude and conduction
      velocity from 2.97 +/- 0.55 mV and 32.8 +/- 3.91 m/s to 0.24 +/- 0.23 mV and 2.72
      +/- 2.72 m/s, respectively (N = 5). All these effects developed slowly and were
      reversible upon 180-min washout.

PMID- 11593311
TI  - Effect of L-arginine, dimercaptosuccinic acid (DMSA) and the association of L
      arginine and DMSA on tissue lead mobilization and blood pressure level in
      plumbism.
AB  - Lead (Pb)-induced hypertension is characterized by an increase in reactive oxygen
      species (ROS) and a decrease in nitric oxide (NO). In the present study we
      evaluated the effect of L-arginine (NO precursor), dimercaptosuccinic acid (DMSA,
      a chelating agent and ROS scavenger), and the association of L-arginine/DMSA on
      tissue Pb mobilization and blood pressure levels in plumbism. Tissue Pb levels
      and blood pressure evolution were evaluated in rats exposed to: 1) Pb (750 ppm,
      in drinking water, for 70 days), 2) Pb plus water for 30 more days, 3) Pb plus
      DMSA (50 mg kg(-1) day(-1), p.o.), L-arginine (0.6%, in drinking water), and the
      combination of L-arginine/DMSA for 30 more days, and 4) their respective matching
      controls. Pb exposure increased Pb levels in the blood, liver, femur, kidney and
      aorta. Pb levels in tissues decreased after cessation of Pb administration,
      except in the aorta. These levels did not reach those observed in nonintoxicated
      rats. All treatments mobilized Pb from the kidney, femur and liver. Pb
      mobilization from the aorta was only effective with the L-arginine/DMSA
      treatment. Blood Pb concentrations in Pb-treated groups were not different from
      those of the Pb/water group. Pb increased blood pressure starting from the 5th
      week. L-arginine and DMSA treatments (4th week) and the combination of L
      arginine/DMSA (3rd and 4th weeks) decreased blood pressure levels of intoxicated
      rats. These levels did not reach those of nonintoxicated rats. Treatment with L
      arginine/DMSA was more effective than the isolated treatments in mobilizing Pb
      from tissues and in reducing the blood pressure of intoxicated rats.

PMID- 11593312
TI  - Actions of Crotalus durissus terrificus venom and crotoxin on the isolated rat
      kidney.
AB  - Many studies have reported the occurrence of lethal acute renal failure after
      snakebites. The aim of the present investigation was to determine alterations in
      renal function produced by Crotalus durissus terrificus venom and crotoxin as
      well as the histological alterations induced by these venoms. Isolated kidneys
      from Wistar rats weighing 240 to 280 g were perfused with Krebs-Henseleit
      solution containing 6 g% of previously dialyzed bovine serum albumin. The effects
      of Crotalus durissus terrificus venom and crotoxin were studied on glomerular
      filtration rate (GFR), urinary flow (UF), perfusion pressure (PP) and percentage
      sodium tubular transport (%TNa+). The infusion of Crotalus durissus terrificus
      venom (10 microg/ml) and crotoxin (10 microg/ml) increased GFR (control80 = 0.78
      +/- 0.07, venom80 = 1.1 +/- 0.07, crotoxin80 = 2.0 +/- 0.05 ml g(-1) min(-1),
      P<0.05) and UF (control80 = 0.20 +/- 0.02, venom80 = 0.32 +/- 0.03, crotoxin80 =
      0.70 +/- 0.05 ml g(-1) min(-1), P<0.05), and decreased %TNa+ (control100 = 75.0
      +/- 2.3, venom100 = 62.9 +/- 1.0, crotoxin80 = 69.0 +/- 1.0 ml g(-1) min(-1),
      P<0.05). The infusion of crude venom tended to reduce PP, although the effect was
      not significant, whereas with crotoxin PP remained stable during the 100 min of
      perfusion. The kidneys perfused with crude venom and crotoxin showed abundant
      protein material in the urinary space and tubules. We conclude that Crotalus
      durissus terrificus venom and crotoxin, its major component, cause acute
      nephrotoxicity in the isolated rat kidney. The current experiments demonstrate a
      direct effect of venom and crotoxin on the perfused isolated kidney.

PMID- 11593313
TI  - GLUT4 protein expression in obese and lean 12-month-old rats: insights from
      different types of data analysis.
AB  - GLUT4 protein expression in white adipose tissue (WAT) and skeletal muscle (SM)
      was investigated in 2-month-old, 12-month-old spontaneously obese or 12-month-old
      calorie-restricted lean Wistar rats, by considering different parameters of
      analysis, such as tissue and body weight, and total protein yield of the tissue.
      In WAT, an approximately 70% decrease was observed in plasma membrane and
      microsomal GLUT4 protein, expressed as microg protein or g tissue, in both 12
      month-old obese and 12-month-old lean rats compared to 2-month-old rats. However,
      when plasma membrane and microsomal GLUT4 tissue contents were expressed as g
      body weight, they were the same. In SM, GLUT4 protein content, expressed as
      microg protein, was similar in 2-month-old and 12-month-old obese rats, whereas
      it was reduced in 12-month-old obese rats, when expressed as g tissue or g body
      weight, which may play an important role in insulin resistance. Weight loss did
      not change the SM GLUT4 content. These results show that altered insulin
      sensitivity is accompanied by modulation of GLUT4 protein expression. However,
      the true role of WAT and SM GLUT4 contents in whole-body or tissue insulin
      sensitivity should be determined considering not only GLUT4 protein expression,
      but also the strong morphostructural changes in these tissues, which require
      different types of data analysis.

PMID- 11593314
TI  - Bronchiolitis obliterans and other late onset non-infectious pulmonary
      complications in hematopoietic stem cell transplantation.
AB  - Pulmonary complications develop in 30-60% of hematopoietic stem cell transplants
      (HSCT). The main, late onset, non-infectious complications include Bronchiolitis
      obliterans (BO), Bronchiolitis obliterans organizing pneumonia (BOOP), and
      idiopathic pneumonia syndrome (IPS). BO and BOOP occur almost exclusively in
      allogeneic HSCT, and have 61% and 21% mortality rates, respectively. BOOP
      responds favorably to corticosteroids. IPS has less than 15% 1-year survival.

PMID- 11593315
TI  - High-dose carboplatin with etoposide in patients with recurrent thymoma: the
      Indiana University experience.
AB  - Thymoma is a chemotherapy-sensitive tumor with a 30-50% 5-year survival in
      previously untreated patients. Unfortunately, durable CRs with salvage
      chemotherapy are rarely observed. We initiated a phase II trial of high-dose
      carboplatin and etoposide in patients with relapsed thymoma or thymic carcinoma.
      All patients had progressive disease (PD) after initial or salvage chemotherapy,
      but were not cisplatin-refractory. PBSCs were mobilized using 10 microg/kg/day G
      CSF. Patients received carboplatin 700 mg/m(2) and etoposide 750 mg/m(2) i.v. on
      days -5, -4, -3. Five patients were enrolled and evaluated after tandem
      transplants 4 weeks apart. All patients had pleural-based and lung parenchymal
      metastasis, one or two prior surgeries and two or more courses of prior cisplatin
      based chemotherapy regimens. Chemotherapy was well tolerated, although grade IV
      hematological toxicity occurred in all patients. Progression-free survival
      following HDC ranged from 3.5 to 16.5 months. One patient maintained a CR for
      12.8 months, then died from an unrelated cause. With a minimum of 2 years follow
      up for all patients, three of five patients remain alive at 26+, 36+, and 49+
      months. High-dose carboplatin and etoposide in relapsed thymoma is feasible with
      acceptable toxicity; however, these limited data do not appear superior to
      standard-dose salvage therapy.

PMID- 11593316
TI  - Effect of interleukin (IL)-12 and IL-15 on apoptosis and proliferation of
      umbilical cord blood mononuclear cells.
AB  - Decreased graft-versus-host disease (GVHD) in cord blood (CB) transplantation may
      be attributed to the immunological immaturity and susceptibility to apoptosis of
      CB mononuclear cells (MNCs). Cytokines like interleukin (IL)-12 and IL-15 may be
      used for in vivoadministration or ex vivo expansion of lymphoid cells for more
      rapid recovery following stem cell transplant, and for providing a graft-versus
      leukemia (GVL) effect. We investigated the effects of IL-12 and IL-15, alone or
      in combination on apoptosis and proliferation of both CB and adult peripheral
      blood (APB) MNCs, with particular emphasis on CB CD4+, CD8+ and CD56+ lymphocyte
      subpopulations. The results of our study indicated that: (1) the combination of
      IL-12+IL-15 resulted in a greater degree of CB and APB apoptosis than either
      cytokine alone; (2) the level of both spontaneous and cytokine-induced apoptosis
      by IL-12 and/or IL-15 are greater in CB MNCs than in APB MNCs using TUNEL assays;
      (3) IL-15 is superior to IL-12 in enhancing the proliferative response in CB and
      APB MNCs; (4) the combination of IL-12+IL-15, but not either cytokine alone,
      significantly enhanced apoptosis in CD8+ and CD56+ CB subsets, but not in CD4+ CB
      subsets; (5) IL-12 or IL-15 alone resulted in increased proliferation in CD4+,
      CD8+ and CD56+ CB subsets, with IL-12+IL-15 producing the greatest increase of
      proliferation in all three CB subsets; and (6) IL-15 and/or IL-12 significantly
      upregulate Fas (CD95) expression on CB T and NK cells. These findings may have
      therapeutic implications when designing cytokine therapy in patients receiving CB
      transplant.

PMID- 11593317
TI  - A short course of induction chemotherapy followed by two cycles of high-dose
      chemotherapy with stem cell rescue for chemotherapy naive metastatic breast
      cancer: sequential phase I/II studies.
AB  - Two cycles of high-dose chemotherapy with stem cell support (HDC) may increase
      the total dose delivered and dose intensity. A brief induction phase and
      different non-cross-resistant agents for each HDC cycle were used to avoid drug
      resistance. Twenty-six women with metastatic BC had induction and stem cell
      mobilization with two cycles of doxorubicin/G-CSF given every 14 days. Patients
      with stable disease or better after induction received HD CTCb followed by HD
      melphalan and dose-escalated paclitaxel. At 475 mg/m(2) of paclitaxel by 24-h
      infusion, dose-limiting transient peripheral sensory neuropathy was encountered.
      No toxic deaths occurred. Complete and near complete response after completion of
      therapy was achieved in 22 (85%) of 26 patients. The median EFS was 38 months.
      The median OS has not yet been reached. At a median follow-up of 33 (25-43)
      months, actuarial EFS and OS were 54% (95% confidence interval (CI), 39-69%) and
      69% (95% CI, 56-79%), respectively. This double transplant approach lasts only 14
      weeks and is feasible, safe, and tolerable. Whilst selection biases may in part
      contribute to favorable EFS and OS, a randomized comparison of standard therapy
      vs double transplant in both metastatic and locally advanced breast cancer is
      warranted.

PMID- 11593318
TI  - Autologous stem cell transplantation for non-Hodgkin's lymphoma: comparison of
      radiation-based and chemotherapy-only preparative regimens.
AB  - The aim of this study was to compare toxicity and efficacy of total body
      irradiation (TBI), cyclophosphamide (CY) and etoposide (E) (TBI/CY/E) vs
      busulfan, melphalan and thiotepa (Bu/Mel/T) in patients receiving autologous stem
      cell infusion (ASCI) for malignant lymphoma (NHL). Between September 1990 and
      July 1998, 351 patients with NHL were treated with TBI/CY/E (n = 221) or Bu/Mel/T
      (n = 130) followed by ASCI. Patients in first, or second remission, first
      responding or untreated relapse were defined as having less advanced disease
      before transplantation. The median follow-up was 5 years (range 1-9) and 3.5
      years (1-6) for patients receiving TBI/CY/E and Bu/Mel/T, respectively. The
      cumulative probabilities of survival, event-free survival (EFS) and relapse at 5
      years were 44%, 32%, 49% following TBI/CY/E and 42%, 34% and 42% following
      Bu/Mel/T. The probability of EFS at 5 years for patients who had prior dose
      limiting radiation (n = 59) was 32% after Bu/Mel/T therapy. Transplant-related
      mortality was 16% for TBI/CY/E and 21% for Bu/Mel/T. In univariate and
      multivariate analyses, more advanced disease status was associated with poor
      outcome (TBI/CY/E: RR 0.70, CI 0.50 to 0.97 P = 0.04; Bu/Mel/T: RR 0.61, CI 0.39
      to 0.97 P = 0.03). No significant differences in toxicities and outcomes were
      observed between these two regimens despite the inclusion of patients who had
      received dose-limiting irradiation in the Bu/Mel/T regimen.

PMID- 11593319
TI  - Lymphocyte reconstitution following non-myeloablative hematopoietic stem cell
      transplantation follows two patterns depending on age and donor/recipient
      chimerism.
AB  - The effect of mixed chimerism on the pace of post-transplant immune
      reconstitution is unknown. Using flow cytometry, recall and neo-antigen vaccine
      responses, and T cell receptor recombination excision circle (TREC)
      quantification, we evaluated phenotypic and functional characteristics of T and B
      cells in nine patients following non-myeloablative, HLA-identical peripheral
      blood stem cell transplantation for chronic granulomatous disease. Engraftment of
      T cell, B cell, and myeloid lineages proceeded at similar paces within each
      patient, but engraftment kinetics segregated patients into two groups: adults,
      who became full donor T cell chimeras before 6 months (rapid engrafters) and
      children, who became full donor T cell chimeras after 6 months or not at all
      (slow engrafters). Quantitative B cell recovery was achieved by 6 weeks after
      transplantation in children, but was delayed until 1 year in adults. Early
      quantitative B cell recovery was not accompanied by an early humoral immune
      response to tetanus toxoid (TT). Emergence of TT-specific T cell responses
      coincided with naive T cell reconstitution, as measured by CD4/CD45RA T cell
      recovery and TREC quantification. These data suggest that immune reconstitution
      occurs faster in pediatric patients who have prolonged mixed hematopoietic
      chimerism compared to adults, who have rapid donor stem cell engraftment.

PMID- 11593320
TI  - The utility of plasma polymerase chain reaction for human herpes virus-6 among
      pediatric bone marrow transplant recipients: results of a pilot study.
AB  - We evaluated the utility of plasma polymerase chain reaction (PCR) for
      surveillance of human herpes virus 6 (HHV-6) infection among pediatric bone
      marrow transplant (BMT) recipients. We used a prospective, non-interventional
      design involving a study group and controls. BMT recipients and healthy controls
      were evaluated. BMT subjects had HHV-6 PCR done biweekly for 12 weeks post
      transplantation, while a single PCR test was done on controls. For the PCR assay,
      EDTA blood was collected and DNA extracted from whole blood and cell-free plasma
      using standard procedures. The PCR was first performed on DNA from whole blood
      and if a positive result was obtained, the test was repeated on the DNA from the
      plasma. Thirty BMT recipients (13 autologous and 17 allogeneic) were enrolled, on
      whom a total of 156 PCR tests were performed, while six tests were done on six
      healthy controls. The median age of BMT subjects was 6.2 years (range 0.5-17.5
      years). The median age of the control subjects was 6.6 years (range 2-10 years).
      Among asymptomatic BMT patients who had PCR surveillance, the positivity rate was
      3.3% (1/30) on whole blood and 0% (0/30) on plasma. None of the six healthy
      subjects had a positive PCR test on whole blood. During the period of the
      surveillance study, 14 patients had diagnostic evaluations for HHV-6 disease
      because of clinical symptoms. Two of these patients were diagnosed with disease
      associated with HHV-6 (graft failure and encephalitis) and had positive PCR tests
      on whole blood and plasma and whole blood and cerebrospinal fluid, respectively.
      We conclude that despite the fact that HHV-6 seropositivity rates are high among
      children, the frequency of HHV-6 plasma PCR positivity is low in pediatric BMT
      subjects who are asymptomatic for HHV-6 disease. Given that a positive test on
      plasma is consistent with active infection, this increases the utility of the PCR
      test as a diagnostic aid in evaluating syndromes presumed to be due to HHV-6 in
      pediatric bone marrow transplant recipients.

PMID- 11593321
TI  - Respiratory virus infections after stem cell transplantation: a prospective study
      from the Infectious Diseases Working Party of the European Group for Blood and
      Marrow Transplantation.
AB  - Community-acquired respiratory virus infections are a cause of mortality after
      stem cell transplantation (SCT). A prospective study was performed at 37 centers
      to determine their frequency and importance. Additional cases were also collected
      to allow the analysis of risk factors for severe infection. Forty episodes were
      collected in the prospective study and 53 additional episodes through subsequent
      case collection. The frequency of documented respiratory virus infections was
      3.5% among 819 allogeneic and 0.4% among 1154 autologous SCT patients
      transplanted during the study period. The frequency of lower respiratory tract
      infections (LRTI) was 2.1% among allogeneic and 0.2% among autologous SCT
      patients. The mortality within 28 days from diagnosis of a respiratory viral
      infection was 1.1% among allogeneic SCT while no autologous SCT patient died. The
      deaths of five patients (0.6%) were directly attributed to a respiratory virus
      infection (three RSV; two influenza A). On multivariate analysis, lymphocytopenia
      increased the risk for LRTI (P = 0.008). Lymphocytopenia was also a significant
      risk factor for LRTI in patients with RSV infections. The overall mortality in
      RSV infection was 30.4% and the direct RSV-associated mortality was 17.4%. For
      influenza A virus infection, the corresponding percentages were 23.0% and 15.3%.
      This prospective study supports the fact that community-acquired respiratory
      virus infections cause transplant-related mortality after SCT.

PMID- 11593322
TI  - A randomised trial comparing cytomegalovirus antigenemia assay vs screening
      bronchoscopy for the early detection and prevention of disease in allogeneic bone
      marrow and peripheral blood stem cell transplant recipients.
AB  - Preemptive antiviral therapy is often employed for CMV prevention following
      allogeneic BMT. Two common strategies are a screening bronchoscopy for CMV post
      BMT or regular CMV antigenemia testing with ganciclovir administration for a
      positive result. In a randomised trial, we prospectively compared the efficacy of
      these two preemptive strategies. Consecutive patients were randomised to either a
      bronchoscopy for CMV on day 35 post BMT or weekly CMV antigenemia testing. If the
      bronchoscopy was positive for CMV, patients received preemptive ganciclovir for 8
      10 weeks. If the antigenemia was positive for CMV, patients received a minimum of
      2 weeks of preemptive ganciclovir. The primary endpoint was the development of
      active CMV disease. One hundred and eighteen allogeneic BMT patients were
      enrolled (60 in the antigenemia arm and 58 in the bronchoscopy arm). The two
      groups were comparable with respect to baseline demographic data, underlying
      disease, conditioning regimen, and immunosuppression. Active CMV disease
      developed in 7/58 (12.1%) patients in the bronchoscopy arm vs 1/60 patients
      (1.7%) in the CMV antigenemia arm (P = 0.022). Based on the screening test, 13.8%
      of patients received preemptive ganciclovir in the bronchoscopy arm vs 48.3% of
      patients in the antigenemia arm (P < 0.001). There was no significant difference
      in the rate of graft-versus-host disease, bacteremia, invasive fungal infections
      or mortality between the two groups. Preemptive therapy based on regular CMV
      antigenemia monitoring is superior to screening bronchoscopy for the prevention
      of CMV disease after allogeneic BMT.

PMID- 11593323
TI  - Infectious complications within the first year after nonmyeloablative allogeneic
      peripheral blood stem cell transplantation.
AB  - Nonmyeloablative peripheral blood stem cell transplantation (PBSCT) is a novel
      therapeutic strategy for patients with malignant and non-malignant hematologic
      diseases. Infectious complications of this procedure have not been previously
      well described. Data on 12 patients transplanted at a tertiary care center were
      collected prospectively and verified retrospectively. Neutropenia developed in a
      third of patients, lasting for a median of 5 days. All patients developed some
      degree of graft-versus-host disease, as intended. Most patients achieved full
      chimerism by week 5. Bacterial infections occurred in two patients (17%).
      Cytomegalovirus (CMV) viremia occurred in five patients (42%) at a median of 80
      days; none had received CMV prophylaxis. Viremia was associated with fever and
      fatigue in three patients, possible gastrointestinal involvement in one patient
      and was asymptomatic in one patient. All viremic patients responded to
      intravenous ganciclovir therapy. No fungal infections were documented. No
      patients died as a result of infection. The incidence of CMV viremia in our
      patients was high, but the incidence of invasive disease due to CMV was low. The
      best strategy to prevent CMV in patients undergoing nonmyeloablative PBSCT
      remains to be determined, but strategies employed in traditional allogeneic bone
      marrow transplantation should be considered in these patients.

PMID- 11593324
TI  - Patterns of Leydig cell insufficiency in adult males following bone marrow
      transplantation for haematological malignancies.
AB  - Gonadal and sexual function are key to quality of life following bone marrow
      transplantation (BMT), but no large studies have been published on Leydig cell
      (LC) function in adults. LC insufficiency (LCI) can cause premature andropause
      with its consequences including sexual morbidity from diminished libido and
      erectile dysfunction (ED). In addition, LCI can result in generalised fatigue and
      even osteopenia. We reviewed gonadal function pre-transplant (immediately prior
      to BMT) and at 3-18 months post BMT in 117 patients who underwent BMT for a
      variety of haematological malignancies. The patients presented with variable
      degrees of symptoms of LCI, such as fatigue, diminished sex drive and libido or
      ED. The results suggest that the patients sustained severe gonadal damage to both
      their germ cells (GC) as well as the LC compartment (P < 0.001). We characterised
      two distinct functional subsets of LC insufficiency: Type I: compensated type
      with high LH and normal T levels and low T/LH ratio: (n = 102); and type II:
      uncompensated type (premature andropause) with high LH and low testosterone
      levels with low T/LH ratio (n = 15). Although type II patients had more severe LC
      damage than type I, patients in both groups were symptomatic. We recommend that
      symptomatic patients in both groups may benefit from a therapeutic trial with
      testosterone replacement treatment (TRT) for 3-6 months.

PMID- 11593325
TI  - Gender-associated differences in the quality of life after allogeneic BMT.
AB  - The purpose of this study was to compare the quality of life (QOL) of male and
      female allogeneic BMT recipients. One hundred and nine BMT patients participated
      in this cross-sectional survey and completed the following instruments:
      Functional Assessment of Cancer Treatment (FACT-BMT version 3), shortened version
      of Profile of Mood States (POMS), MOS Survey of Social Support, and A Brief
      Measure of Social Support (SSQ6). Independent of the time post-BMT, perceived
      physical well-being, age at BMT, and education, females reported worse emotional
      well-being and more fatigue than males. Females also indicated more tiredness and
      less quality sleep. Males were found to experience less satisfaction with social
      support regardless of marital status. On the other hand, married males were more
      satisfied with their sexual life, more interested in sexual relationships, and
      more sexually active compared to married females. However, no significant
      differences between males and females were found in terms of overall physical,
      functional, and social well-being assessed by the FACT-BMT. The present results
      indicated that important gender differences exist among allogeneic BMT recipients
      which need to be addressed when designing post-treatment intervention programs
      for BMT recipients.

PMID- 11593326
TI  - Standardisation of multiplex fluorescent short tandem repeat analysis for
      chimerism testing.
AB  - To evaluate the origin of cells after allogeneic haematopoietic stem cell
      transplantation we optimised and evaluated two commercially available systems
      (AmpFlSTR Profiler Plus and GenePrint Powerplex-16) which are based on multiplex
      fluorescent short tandem repeat (STR) analysis. A standard procedure for
      interpretation of electropherographs was found essential to obtain reproducible
      results. On the basis of the relative length of donor and recipient alleles, TYPE
      I (no shared alleles are used to calculate chimerism), TYPE-II (one shared and
      one unshared allele is used to calculate chimerism) or TYPE-III (not informative)
      allelic distribution types were distinguished. Also, stutter peaks were
      recognised as an important criterion to exclude a marker for analysis.
      Intralaboratory and multicentre evaluation of the AmpFlSTR Profiler Plus system
      showed that mixed blood samples could be determined with an absolute deviation of
      less than 2%. A sensitivity threshold was set at 5% for TYPE-I and 10% for TYPE
      II markers since relative imprecision increases at low chimerism values. No
      significant difference of calculated chimerism values was observed between STR
      markers shared between both systems. By monitoring 26 allogeneic peripheral blood
      stem cell transplants, the applicability of the proposed method was demonstrated.

PMID- 11593327
TI  - Allogeneic bone marrow transplantation-mediated transfer of specific immunity
      against Toxocara canis associated with excessive IgE.
AB  - A girl with myelodysplastic syndrome (RAEB-T) received HLA-identical bone marrow
      from her younger brother after myeloablative treatment with busulfan and
      cyclophosphamide. After bone marrow transplantation, fever, exanthema, pruritus,
      and a pulmonary infiltrate were treated symptomatically. Bacterial cultures
      remained negative. Leukocyte engraftment began on day 10, and all blood cell
      populations proved to be of donor origin on FISH analysis. Increasing IgE levels
      (21 000 U/ml) on day 14 after BMT, positive RAST, specific IgG-antibodies, and
      missing Toxocara (T.) canis antigens in the recipient indicated donor-derived
      seroconversion. Before BMT, the recipient had been negative for T. canis in
      routine parasitological screening, and the donor proved to be positive for T.
      canis antibody by ELISA. This report suggests that the transfer of IgE immunity
      in the absence of detectable antigens may be responsible for IgE-mediated
      symptoms consistent with toxocara infection and confirms the need for parasite
      screening in donor medical examinations.

PMID- 11593328
TI  - Successful bone marrow transplantation for severe aplastic anemia following
      orthotopic liver transplantation: long-term follow-up and outcome.
AB  - Severe aplastic anemia (SAA) is well described in children following liver
      transplantation for fulminant hepatic failure (FHF) secondary to non-A, non-B,
      non-C hepatitis, and is associated with a high mortality rate. Successful
      immunosuppressive treatment of SAA following liver transplantation has been
      reported, but death from infectious complications is not uncommon. We report the
      8-year follow-up of a 3.5-year-old boy who underwent successful HLA-identical
      sibling donor bone marrow transplant for SAA 7 months following orthotopic liver
      transplant for non-A, non-B, non-C hepatitis. His post-bone marrow
      transplantation course was uneventful with no evidence of liver toxicity. Eight
      months following BMT he developed renal cell carcinoma metastatic to lymph nodes
      which was treated surgically. Six years following BMT he developed a
      mucoepidermoid carcinoma of the parotid gland also treated surgically. Despite
      these malignancies, he is currently well 8 years following liver and bone marrow
      transplantation, without signs of GVHD, growth failure or liver graft rejection.
      This is the first report of long-term follow-up of bone marrow transplantation
      for SAA following liver transplantation. The occurrence of two subsequent
      malignancies in this child underscores the need for close follow-up of future
      similar cases.

PMID- 11593329
TI  - Quality control for the diagnosis of Toxoplasma gondii reactivation in SCT
      patients using PCR assays.

PMID- 11593330
TI  - Growth suppression of established human osteosarcoma lung metastases in mice by
      aerosol gene therapy with PEI-p53 complexes.
AB  - Lung metastases are a frequent complication of osteosarcoma and a treatment that
      would reduce the severity of this complication would be of great benefit to
      patients. We have used a formulation consisting of polyethyleneimine (PEI) and a
      p53 gene administered in aerosol to treat established lung micrometastases as a
      model of human osteosarcoma in nude mice. The SAOS-LM6 cell line, a metastatic
      derivative of the p53 null SAOS-2 line, expresses high levels of p53 protein
      after in vitro transfection with PEI-p53 complexes as determined by ELISA, and
      transfection with both p53wt and the p53 variant, p53-CD(1-366) in vitro, results
      in a marked inhibition of SAOS-LM6 cell proliferation. Aerosol delivery of
      plasmid DNA containing either the p53 gene or a p53-CD(1-366) variant gene
      formulated with PEI to mice resulted in highly significant reductions in the
      numbers and size of tumors (P<.001), the total number of tumor foci in the lungs
      (P<.001) and the size of individual tumor nodules in treated animals compared to
      untreated, PEI only-treated and PEI-CAT-treated control animals. The different
      tissues examined did not reveal any signs of toxicity or inflammation after
      repeated exposure to PEI-DNA. The aerosol delivery of PEI-based formulations of
      p53 or synthetic p53 variant genes represents a promising new strategy for the
      treatment of established human osteosarcoma lung metastases. The noninvasive
      nature of aerosol delivery coupled with low toxicity also make this therapeutic
      approach potentially appropriate for combination therapy with either radio- or
      chemotherapy.

PMID- 11593331
TI  - Prostate-specific targeting using PSA promoter-based lentiviral vectors.
AB  - The prostate-specific antigen (PSA) promoter is known to be highly tissue
      specific. Although its tissue specificity has been confirmed, its efficiency of
      gene transcription is significantly lower compared to known nonspecific viral
      promoters. These lower levels of promoter activity therefore pose a problem when
      developing an efficacious gene vector for prostate cancer gene therapy. Thus,
      selecting an appropriate therapeutic gene and vector system to carry the gene
      driven by the PSA promoter (PSAP) is important. In the studies described here, a
      human immunodeficiency virus (HIV)-1-based lentiviral vector carrying either the
      enhanced green fluorescent protein (EGFP) reporter or the diphtheria toxin A
      (DTA) gene was constructed. The results demonstrate that the PSA promoter in a
      lentiviral vector drives genes in prostate cells with satisfactory efficacy and
      specificity. The tissue-specific expression of the DTA protein efficiently
      eradicates LNCaP prostate cells in culture. We also infected prostate cancer
      cells and control cells carried by nude mice with the EGFP lentiviral vector.
      Significant numbers of EGFP-positive LNCaP cells were detected in all the mice
      bearing these tumors, but no EGFP-positive control cells were detected in any
      other mouse tissue. The high levels of expression in prostate cells, compared
      with the low levels of background expression in other cells, show that the PSAP
      lentiviral vector could be a potential useful tool for gene therapy of metastatic
      prostate cancer.

PMID- 11593332
TI  - Endothelial cell-based systemic gene therapy of metastatic melanoma.
AB  - Cancer metastasis accounts for a significant proportion of morbidity and
      mortality in patients. Effective means of treating disseminated disease remains
      elusive. The purpose of this study was to determine whether genetically modified
      endothelial cells (GMEC) can selectively target and deliver recombinant
      therapeutic molecules to sites of tumor metastases. Following the establishment
      of lung metastases of 4T1 mammary tumor in mice, intravenously (i.v.)
      administered, lacZ transgene-expressing endothelial cells (lacZ-GMEC) accumulated
      at the tumor sites. An average of 32% and 90% of the pulmonary metastases were X
      gal stained following one and three tail vein injections of 10(5) lacZ-GMEC,
      respectively. The linear pattern of X-gal staining seen within the tumor sites
      and the histological appearance of the tumor vasculature were consistent with the
      incorporation of lacZ-GMEC into blood vessels. In C57Bl/6 mice harboring lung
      metastases of melanoma, the administration of three sequential i.v. injections of
      10(5) endothelial cells expressing a human interleukin 2 transgene abrogated the
      tumor metastases and prolonged survival of the animals. These results demonstrate
      that i.v.-administered GMEC can selectively accumulate, survive, and stably
      express exogenous genes at multiple tumor sites. These findings support a role
      for i.v.-administered GMEC as a potential therapeutic strategy for the systemic
      treatment of cancer metastases.

PMID- 11593333
TI  - Heat-inducible TNF-alpha gene therapy combined with hyperthermia using magnetic
      nanoparticles as a novel tumor-targeted therapy.
AB  - Heat-induced therapeutic gene expression is highly desired for gene therapy to
      minimize side effects. Furthermore, if the gene expression is triggered by heat
      stress, combined therapeutic effects of hyperthermia and gene therapy may be
      possible. We combined TNF-alpha gene therapy driven by the stress-inducible
      promoter, gadd 153, with hyperthermia using magnetite cationic liposomes (MCLs).
      In nude mice, MCLs induced cell death throughout much of the tumor area on
      heating under an alternating magnetic field. This heat stress also resulted in a
      3-fold increase in TNF-alpha gene expression driven by the gadd 153 promoter as
      compared with that of nonheated tumor. TNF-alpha gene expression was also
      observed in the peripheral area where the hyperthermic effect was not enough to
      cause cell death. The combined treatment strongly arrested tumor growth in nude
      mice over a 30-day period, suggesting potential for cancer treatment.

PMID- 11593334
TI  - Immunogenicity of nonreplicating recombinant vaccinia expressing HLA-A201
      targeted or complete MART-1/Melan-A antigen.
AB  - The effect on immunogenicity of different tumor T cell epitope formulations was
      evaluated in vitro using nonreplicating recombinant vaccinia vector expressing
      two forms of the melanoma-associated MART-1/Melan-A antigen. The first
      recombinant virus expressed a minigene encoding a fusion product between an
      endoplasmic reticulum (ER)-targeting signal and the HLA-A201 binding 27-35
      peptide. The second viral construct encoded the complete MART-1/Melan-A protein.
      The capacity of HLA-A201 cells infected with either viral construct to generate
      and to stimulate MART-1/Melan-A 27-35 specific cytotoxic T-lymphocytes (CTL), was
      comparatively characterized. The results obtained here with a tumor antigen
      confirmed the capacity of vaccinia virus-encoded ER-minigene to generate a very
      strong antigenic signal. In cytotoxicity assays, recognition of target cells
      infected with high amounts of both recombinant viruses with activated specific
      CTL clones, resulted in similar lytic activity. With regard to calcium
      mobilization, TCR down-regulation, IFN-gamma release, and T cell proliferation
      assays, the targeted epitope elicited 10- to 1000-fold stronger responses.
      Remarkably, the immunogenic difference between the two formulations, in their
      respective capacity to generate CTL from naive HLA-A2 peripheral blood
      mononuclear cells in vitro as measured by tetramer detection, was lower (2- to 3
      fold). Recombinant vectors expressing complete antigens have demonstrated their
      capacity to generate specific responses and such vaccines might take advantage of
      a broader potential of presentation. However, as demonstrated here for the HLA
      A201-restricted MART-1/Melan-A immunodominant epitope, nonreplicative vaccinia
      virus expressing ER-targeted minigenes appear to represent a significantly more
      immunogenic epitope vaccine formulation.

PMID- 11593335
TI  - Temozolomide enhances herpes simplex virus thymidine kinase/ganciclovir therapy
      of malignant glioma.
AB  - Gene therapy for malignant glioma with the herpes simplex virus thymidine
      kinase/ganciclovir (HSV-tk/GCV) system is already in the stage of clinical
      trials, but still needs major improvement to achieve greater clinical efficacy.
      The aim of this study was to determine whether combining HSV-tk/GCV gene therapy
      with temozolomide (TMZ), an alkylating drug clinically proven to be efficient in
      recurrent high-grade gliomas, would result in enhanced antitumor effect in
      malignant glioma in culture and in vivo. Human U87MG glioblastoma (GBM) cells
      with or without expression of HSV-tk were treated with different concentrations
      of GCV, TMZ, or both drugs. Cell viability was accessed by an automated
      microplate assay (MTT). The isobologram method and the combination index (CI)
      method of Chou-Talalay were used to measure the interactions between the two
      drugs when applied simultaneously. U87-tk and control U87 cells (5x10(6) each)
      were implanted in the flanks of nude mice, and animals were treated with GCV or
      TMZ or with both drugs. All tumors were measured and weighed at specified time
      points. IC(50) for GCV was 511 microM in control U87 cells and 14.3 microM in U87
      tk cells, resulting in 35.7-fold increase of toxicity in the HSV-tk-expressing
      cells. TMZ had an IC(50) of 20.2 mM in control cells and 2.35 mM in U87-tk cells,
      resulting in 8.6-fold increase in sensitivity of the HSV-tk-expressing cells. TMZ
      and HSV-tk/GCV actions were synergistic (CI<1) in both control and U87-tk cells
      with higher synergism in U87-tk cells at high effect levels. Tumors expressing
      HSV-tk and treated with TMZ and GCV were significantly smaller than those treated
      by TMZ, but not by GCV. There was also a significant difference between the
      weight of HSV-tk expressing versus control tumors treated with TMZ, with GCV, or
      with both drugs. These data demonstrate synergism between HSV-tk/GCV and TMZ and
      higher sensitivity against TMZ in HSV-tk-expressing GBM cells. The potential
      importance for clinical studies combining both local tumor gene therapy and
      systemic chemotherapy should be explored further.

PMID- 11593336
TI  - Selection of drug-resistant transduced cells with cytosine nucleoside analogs
      using the human cytidine deaminase gene.
AB  - Hematopoietic toxicity produced by most anticancer drugs limits their potential
      for curative therapy. We have shown previously that the human cytidine deaminase
      (CD) gene can confer drug resistance in murine bone marrow cells (BMCs) to the
      nucleoside analog, cytosine arabinoside (ARA-C). In the present study, as the
      first objective we showed that the CD gene can also render drug resistance in
      BMCs to related analogs, 2',2'-difluorodeoxycytidine (dFdC) and 5
      azadeoxycytidine (5-AZA-CdR). As a second objective, we investigated the
      potential of ex vivo selection with cytosine nucleoside analogs of CD-transduced
      BMC. The goal of this approach was to enrich the fraction of CD-transduced BMCs
      so as to increase the transgene expression and level of drug resistance before
      transplantation. This strategy may have the potential to circumvent the problem
      in clinical gene therapy of low level of gene transfer and adequate long-term
      gene expression. Using a bicistronic retroviral vector containing the CD and the
      green fluorescent protein (CDiGFP), we transduced murine L1210 leukemic cells.
      All three analogs, ARA-C, dFdC, and 5-AZA-CdR were demonstrated in vitro to
      enrich (>95%) the population of leukemic cells expressing the GFP transgene.
      However, with CD-transduced primary murine BMCs cultivated at high cell density
      we observed that in vitro selection with ARA-C was not possible due to release of
      CD into the culture medium at amounts that were sufficient to inactivate the
      analog. The CD-containing medium produced a chemoprotective effect on mock BMCs
      as shown by lack of significant growth inhibition in the presence of ARA-C.
      However, at low cell density in a cell mixture containing CD-transduced cells,
      the mock BMCs showed marked drug sensitivity to ARA-C as determined by clonogenic
      assay. Selection with ARA-C was shown to significantly increase the CD enzyme
      activity in transduced BMC. These results suggest that CD gene has the potential
      to be a good selectable marker and a possible tool for chemoprotection in cancer
      gene therapy.

PMID- 11593338
TI  - Highlights of the Second International Symposium on Genetic Anticancer Agents.

PMID- 11593341
TI  - Effects of health measurements and health information in youth and young
      adulthood in dietary intake--20-y study results from the Amsterdam Growth and
      Health Longitudinal Study.
AB  - BACKGROUND: The Amsterdam Growth and Health Longitudinal Study (AGAHLS) is a 20 y
      observational study concerning biological, psychological and lifestyle risk
      factors for cardiovascular disease and osteoporosis. In the AGAHLS two cohorts
      can be distinguished: the so-called Multi-Measurement Group (MMG), which received
      eight repeated measurements, and a Bi-Measurement Group (BMG), which received two
      measurements, one at the beginning and one at the end of the 20 y period.
      OBJECTIVE: In health-related longitudinal research, the outcomes of the study may
      be influenced by the measurements themselves and the health information provided.
      It was hypothesized that the repeated measurements and the health information
      given to the MMG would result in a more healthy dietary intake in comparison to
      the BMG. DESIGN: The MMG consisted of 164 subjects and the BMG consisted of 90
      subjects. At the start of the study, subjects were teenagers of 13-y-old. The
      hypothesis was tested with use of regression analysis, analysing group
      differences in mean individual change scores. RESULTS: Only the MMG showed a
      significantly larger decrease in the intake of mono- and disaccharides compared
      to the BMG. CONCLUSIONS: The effect of the repeated measurements and the health
      information provided on dietary intake was relatively small, since it was only
      one out of the 14 nutrients that differed between the MMG and the BMG.

PMID- 11593342
TI  - Alcohol drinking and risk of non-Hodgkin's lymphoma.
AB  - OBJECTIVE: To analyse the relation between alcohol intake and the risk of non
      Hodgkin's lymphoma (NHL). DESIGN: Hospital-based case-control study. SETTINGS:
      The greater Milan area and the province of Pordenone, Northern Italy. SUBJECTS:
      Cases were 446 (256 men and 190 women) with histologically confirmed incident
      NHL, and controls were 1295 (791 men and 504 women) with acute non-neoplastic
      conditions. RESULTS: Compared to non-drinkers, the odds ratio (OR) was 0.92 for
      <3 drinks per day, 0.98 for 3-6 drinks, and 1.02 for > or =7 drinks per day. Wine
      drinking was also not associated with risk, and the OR was 0.85 for drinkers of >
      or =7 drinks/day compared to non-drinkers. Beer and spirit intake was also not
      associated with NHL risk. CONCLUSIONS: Our study, based on a population with
      relatively high alcohol intakes, indicates that there is no appreciable
      association between intake of various alcoholic beverages and the risk of NHL.
      SPONSORSHIP: Italian Association for Research on Cancer, Milan, Italy.

PMID- 11593343
TI  - Very-long-chain omega-3 fatty acids as markers for habitual fish intake in a
      population consuming mainly lean fish: the EPIC cohort of Gipuzkoa. European
      Prospective Investigation into Cancer and Nutrition.
AB  - OBJECTIVE: To assess the relationship between habitual fish intake and fatty acid
      levels in serum as well as in the LDL fractions of serum phospholipids and
      cholesteryl esters. DESIGN: Cross-sectional study. SETTING: Cohort of Gipuzkoa
      (Basque Country, northern Spain) included in the European Prospective
      Investigation into Cancer and Nutrition (EPIC) project. SUBJECTS: Random sample
      of 120 healthy volunteers of both sexes aged 35-65 y, divided into various
      consumption groups according to daily fish intake. METHODS: Data on habitual
      intake over the previous year was collected by trained interviewers by means of a
      computerized questionnaire based on the diet history method. Fasting venous blood
      samples were drawn and fatty acids were measured by gas-liquid chromatography.
      RESULTS: Lean fish accounted for 78% of all fish consumption in the highest
      consumption group (>115 g/day) and for 60% in the lowest (<31 g/day). The mean
      concentrations of omega-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic
      acid (EPA, C20:5, omega-3), and docosahexaenoic acid (DHA, C22:6, omega-3) in
      serum and in the LDL fractions of serum phospholipids and cholesteryl esters
      increased significantly from the lowest to the highest fish consumption
      categories. Fish intake showed a statistically significant relationship with
      omega-3 PUFA, EPA and DHA in serum and in the LDL fractions of serum
      phospholipids and cholesteryl esters both in the simple linear regression
      analysis and in a multiple regression model adjusted by age, body mass index
      (BMI) and vegetable intake. CONCLUSIONS: Habitual fish intake is reflected in the
      content of EPA and DHA in serum and in the LDL phospholipid and cholesteryl
      esters fractions. The concentrations of very-long-chain omega-3 fatty acids are
      useful biomarkers for dietary fish intake, mainly lean fish. SPONSORSHIP: Europe
      Against Cancer Programme of the European Union (agreement SOC 97 200302 05F02);
      'Fondo de Investigaciones Sanitarias', Spanish Ministry of Health (FIS grant
      99/0024-05); Government of the Basque Country; and 'Fundacion Cientifica de la
      Asociacion Espanola contra el Cancer'.

PMID- 11593344
TI  - Unusually high prevalence rates of obesity in four Mexican rural communities.
AB  - OBJECTIVE: To establish the nutritional status of previously studied rural
      populations. DESIGN AND SUBJECTS: A total of 139 households with 245 males and
      301 females from four relatively isolated Mexican rural communities were randomly
      selected to be surveyed in 1996. RESULTS: Underweight was not a problem in either
      children or adults. In children <5 y only three (4.2%) were stunted but the age-
      and sex-specific distributions of body mass index (BMI) in children showed 17% of
      boys and 19% of girls exceeded the proposed International Obesity Task Force
      limits for classifying the overweight. Triceps skinfold values were similar to
      NHANESI values for white USA children. Of the adult men 42% were overweight (BMI
      25.0-29.9) and 9% obese; 40% of adult women were overweight and a further 33%
      obese. Adjusting BMI values with corrected total heights by relating them to
      measured knee height reduced the BMI of women >50 y by 2.0 units; the male data
      were essentially unchanged. The prevalence of abdominal obesity in women, based
      on waist measurements and WHO cut-off points was high with 25% of women having
      elevated values despite a normal BMI; 43% of the overweight women had substantial
      increases in waist measurements, indicative of high risk, as did 91% of obese
      women. The men's waist measurements were greater in relation to both BMI and body
      fat but the prevalence of values in excess of the suggested sex-specific WHO
      limits was less than half that of women. CONCLUSIONS: The high prevalence of
      overweight and obesity is now evident in poor and relatively isolated rural
      communities of Mexico. SPONSORSHIP: The Chronic Disease Office, from the Ministry
      of Health in Mexico partially financed this study.

PMID- 11593345
TI  - Complementary feeding practices and dietary intakes from complementary foods
      amongst weanlings in rural Malawi.
AB  - OBJECTIVE: The objectives of this study were to estimate the quantity and
      nutritive quality of the complementary diet in rural Malawi, and to identify
      feeding practices, nutrients and dietary modifiers of iron and zinc
      bioavailability that may limit the quality of the diet. DESIGN: This cross
      sectional study design included an anthropometric survey, a feeding practices
      questionnaire, and an interactive, 24 h recall dietary data survey. SETTING: Four
      rural villages in Balaka district, southern Malawi. SUBJECTS: Mothers resident in
      the study communities with breastfed children aged up to 24 months were eligible.
      RESULTS: Stunting was prevalent among these weanlings. Maize was the predominant
      food source, with limited contribution of animal foods. Deficits in dietary
      energy and several nutrients were found when compared to estimated needs. When
      expressed per kg body weight, energy intakes appeared adequate. The
      bioavailability of zinc was low due to a high phytate:zinc molar ratio. Iron
      bioavailability was also low due to low intake of absorption enhancers such as
      meat/fish/poultry protein and ascorbic acid. Dietary quality was poorest for 6 to
      8-month-old infants. CONCLUSIONS: Iron, zinc and calcium were the most limiting
      nutrients to the quality of the diet, partly exacerbated by the poor
      bioavailability of iron and zinc. Increased total intake and bioavailability of
      iron and zinc would improve the complementary diets. SPONSORSHIP: This study was
      funded by the Thrasher Research Fund, Salt Lake City, Utah, USA.

PMID- 11593346
TI  - Intake of sweet foods and counts of cariogenic microorganisms in obese and normal
      weight women.
AB  - OBJECTIVE: To study the intake of sweet foods in obese and normal-weight women,
      while also taking menstrual cycle effects on eating behaviour into consideration.
      An objective test of the intake of sugar-containing foods was introduced by
      measuring salivary counts of mutans streptococci and lactobacilli. DESIGN: A
      cross-sectional comparison of the intake of sweet foods in obese and normal
      weight women. The obese women were also studied longitudinally after 10 weeks in
      a weight reduction programme. SUBJECTS: Obese (n=72, body mass index (BMI) 42.0+/
      5.2 kg/m2) and normal-weight women (n=67, BMI 22.2+/-1.6 kg/m2) participated.
      RESULTS: Mutans streptococci in saliva were higher in obese than in normal-weight
      women (P<0.0001), although the reported habitual daily intake of sweet foods did
      not differ. Of the menstruating women, 80% of the obese subjects and 62% of the
      normal-weight ones (P<0.05) reported periods during the menstrual cycle with an
      'extra large' intake of sweet foods; these intakes were higher in obese than in
      normal-weight women (P<0.01). The obese women reduced their intake of sweet foods
      after 10 weeks of weight reduction, although these changes were not pronounced
      enough to significantly affect the counts of cariogenic microorganisms.
      CONCLUSIONS: In contrast to most previous cross-sectional studies, this study
      shows that obese women have a higher intake of sweet foods, especially pre
      menstrually. This was indicated by higher salivary counts of cariogenic
      microorganisms. SPONSORSHIP: Karolinska Institute Research Funds.

PMID- 11593347
TI  - Homocysteine and methylmalonic acid levels in pregnant Nepali women. Should
      cobalamin supplementation be considered?
AB  - OBJECTIVE: The aim of this study was to investigate homocysteine and
      methylmalonic acid levels as markers of functional cobalamin and folate status in
      pregnant Nepali women. DESIGN: Cross-sectional study. SETTING: Patan Hospital,
      Kathmandu, Nepal. SUBJECTS: A sub-sample (n=382) of all pregnant women (n=2856)
      coming for their first antenatal visit in a 12 month period, 1994-1995. The
      selection of the sub-sample was based on maternal haematocrit values, categorised
      into three groups: severely, moderately and non-anaemic women. As serum levels of
      total homocysteine (s-tHcy) and methylmalonic acid (s-MMA) were similar in the
      three groups, pooled data are presented. Women who had already received
      micronutrient supplementation (n=54) were excluded. The remaining women (n=328)
      were included in the statistical analysis. RESULTS: Overall mean values (+/-s.d.)
      of s-tHcy and s-MMA were 9.5 (+/-4.2) micromol/l and 0.39 (+/-0.32) micromol/l,
      respectively. Elevated s-tHcy (>7.5 micromol/l) was found in 68% of the women,
      while 61% had elevated s-MMA (>0.26 micromol/l). Low s-cobalamin values (<150
      pmol/l) were observed in 49% of the women, while only 7% had low s-folate values
      (< or =4.5 nmol/l). s-tHcy was significantly correlated with s-MMA (r=0.28,
      P<0.001), s-cobalamin (r=-0.30, P<0.001) and s-folate (r=-0.24, P<0.001). s-MMA
      was significantly associated with s-cobalamin (r=-0.40, P<0.001), but not with s
      folate. CONCLUSIONS: Functional cobalamin deficiency was very common in the study
      population, while functional folate deficiency was rather uncommon. We suggest
      considering cobalamin supplementation to pregnant Nepali women. SPONSORSHIP: The
      Norwegian Research Council and the Norwegian Universities Committee for
      Development, Research and Education.

PMID- 11593349
TI  - Evaluation of dietary quality in relationship to nutritional and lifestyle
      factors in elderly people of the US Framingham Heart Study and the European
      SENECA study.
AB  - OBJECTIVE: To evaluate dietary quality of European and American elderly subjects
      using different derivatives of dietary patterns (dietary scores and clusters) and
      to investigate the relationship of these approaches to nutritional and lifestyle
      factors. DESIGN: Data from the cross-sectional SENECA baseline study and
      Framingham Heart Study (original cohort and offspring) were used for data
      analysis. Food intake data were summarised into dietary clusters and into dietary
      scores (Healthy Diet Indicator and Mediterranean Diet Score). These measures of
      dietary quality were then tested for associations with lifestyle factors and
      measures of nutritional status. SUBJECTS/SETTING: The study population, aged 70
      77 y, consisted of 828 subjects from Framingham, MA (USA) and 1282 subjects from
      the following European centres: Hamme, Belgium; Roskilde, Denmark; Padua, Italy;
      Culemborg, The Netherlands; Vila Franca de Xira, Portugal; Betanzos, Spain; and
      Yverdon, Burgdorf and Bellinzona, Switzerland. RESULTS: Dietary intake varied
      widely across the European and American research centres. In general, Southern
      European centres and Framingham had higher mean diet scores, indicating a higher
      dietary quality, than Northern European centres (MD-scores: 4.2-4.4 vs 2.7-3.5).
      Cluster analysis identified the following five dietary patterns characterised by:
      (1) sugar and sugar products; (2) fish and grain; (3) meat, eggs and fat; (4)
      milk and fruit; and (5) alcohol intake. The meat, eggs and fat pattern had
      significantly lower average dietary quality, as measured with all three diet
      scores than all other groups except the alcohol group. The fish and grain group
      had significantly better Mediterranean diet scores than all other groups.
      CONCLUSIONS: Dietary scores and dietary clusters are complementary measures to
      classify dietary quality. The associations with nutritional and lifestyle factors
      indicate the adequate categorisation into dietary quality groups. SPONSORSHIP:
      European Union, US Department of Agriculture, Agriculture Research Service, under
      agreement (58-1950-9-001), Haak Bastiaanse-Kuneman Foundation.

PMID- 11593348
TI  - Short-term changes of cardiovascular risk factors after a non-pharmacological
      body weight reduction program.
AB  - OBJECTIVE: To test the short-term effectiveness of a 3 week hospital-based body
      weight reduction (BWR) program on selected coronary heart disease (CHD) risk
      factors in obese subjects. DESIGN: Intervention study to assess the modifications
      in CHD risk factor scores estimated according to Framingham risk factor
      categories (age, total cholesterol, high density lipoprotein (HDL) cholesterol,
      blood pressure, diabetes and smoking). SETTING: 3rd Division of Metabolic
      Diseases, Italian Institute for Auxology, Piancavallo (VB), Italy. SUBJECTS: Two
      hundred and sixty-eight obese patients (43 men, 225 women, age range 19-81 y;
      body mass index (BMI) range 30-67). INTERVENTION: The BWR program consisted of a
      3 week integrated energy-restricted diet (1200-1800 kcal/day), associated with
      moderate aerobic exercise, psychological counselling and educational lectures.
      RESULTS: Substantial reductions of total cholesterol (16.7%), HDL cholesterol
      (14.8%), systolic (11.2%) and diastolic blood pressure (8.7%) were observed at
      the end of the intervention, even with relatively moderate decrease in weight
      (4.1%) and in persistence of elevated BMI (over 40 kg/m2). The mean CHD
      Framingham score decreased by 16.1%, from 7.8 to 6.2. The BWR-induced changes
      were similar in both sexes, and across strata of age and BMI. CONCLUSIONS: The
      full-time participation of the patients in the hospital-based, integrated BWR
      program may explain the positive clinical outcome in all the subgroups
      considered, although the long-term results need to be quantified. SPONSORSHIPS:
      Partially supported by Progetti di Ricerca Corrente, Istituto Auxologico
      Italiano, IRCCS, Milan, Italy.

PMID- 11593350
TI  - Effects of regular ingestion of black tea on haemostasis and cell adhesion
      molecules in humans.
AB  - OBJECTIVE: To assess the effects in humans of regular ingestion of black tea on
      haemostasis-related variables and cell adhesion molecules. DESIGN: Twenty-two
      subjects were recruited from the general population to a randomised-controlled
      crossover study. Subjects stopped drinking tea, apart from that provided, for the
      duration of the study. During a 4-week baseline period all subjects drank 5
      cups/day (250 ml) of hot water. The effects of 5 cups/day of black tea for 4
      weeks were then compared with hot water. Platelet aggregation in response to
      three doses of collagen and ADP, plasma concentrations of coagulation and
      fibrinolytic factors (fibrinogen, factor VII, tPA, PAI-1) and plasma
      concentrations of cell adhesion molecules (soluble P-selectin, E-selectin, ICAM
      1, VCAM-1) were assessed twice, one week apart, at the end of each period. Twenty
      four hour urinary concentration of 4-O-methylgallic acid (4OMGA), assessed once
      at the end of each period, was used as a marker of black tea polyphenol intake.
      RESULTS: The 24 h urinary excretion of 4OMGA was increased during regular
      ingestion of black tea in comparison to hot water (P<0.0001). Black tea resulted
      in lower soluble P-selectin (P=0.01) in comparison to hot water, but did not
      influence other adhesion molecules. Soluble P-selectin was significantly
      correlated with mean collagen-stimulated platelet aggregation at baseline
      (r=0.61, P=0.003), and during regular ingestion of hot water (r=0.70, P<0.0001)
      and black tea (r=0.51, P=0.01). However, platelet aggregation was not different
      between the black tea and hot water periods for collagen- or ADP-stimulated
      aggregation at any dose. Coagulation and fibrinolytic factors were also not
      different between periods. CONCLUSIONS: The effect of black tea on soluble P
      selectin provides a potential mechanism for cardiovascular benefits of regular
      ingestion of tea. SPONSORSHIP: This study was supported by grants from the Tea
      Trade Health Research Association and the National Heart Foundation of Australia.

PMID- 11593351
TI  - Giessen Wholesome Nutrition Study: relation between a health-conscious diet and
      blood lipids.
AB  - OBJECTIVE: To study in humans the relationship between a diet consistent with
      most of the current recommendations for the prevention of nutrition-related
      diseases (Wholesome Nutrition) and the blood lipid profile (total cholesterol,
      LDL-, HDL-cholesterol, LDL/HDL-ratio, triglycerides). DESIGN: Cross-sectional
      study with two diet groups. SETTING: Former West Germany. SUBJECTS: Healthy women
      (n=243, aged 25-65 y) adhering to Wholesome Nutrition for at least 5 y
      (subdivided into 111 ovo-lacto vegetarians and 132 low-meat eaters) and an
      according control group of 175 women eating an average German mixed diet. They
      were all recruited through an advertisement campaign and selected on the basis of
      their food consumption. RESULTS: Considering potential confounders, the Wholesome
      Nutrition subgroups had higher HDL-cholesterol levels than the control group. No
      differences were observed for total cholesterol and LDL-cholesterol. For LDL/HDL
      ratio and triglycerides the effect of diet was dependent on interaction terms.
      With increasing risk factors (age or body mass index (BMI)) the Wholesome
      Nutrition subgroups showed more favourable blood lipids. CONCLUSIONS: Women
      eating a preventive diet on a long-term basis exhibit more favourable blood lipid
      profiles than women consuming an average mixed diet. This is particularly obvious
      for HDL-cholesterol in the presence of certain risk factors and when an ovo-lacto
      vegetarian version is practised. SPONSORSHIP: Eden Foundation, Bad Soden,
      Germany.

PMID- 11593352
TI  - Variations in the measurement of resting energy expenditure in children with
      cystic fibrosis.
AB  - OBJECTIVE: To investigate in children with cystic fibrosis (CF) and children
      without CF: (1) the test-retest reproducibility of a 20 min resting energy
      expenditure (REE) measurement; and (2) the long-term reproducibility of REE
      measurements in children with CF using longitudinal data. DESIGN: Cross-sectional
      study and longitudinal cohort. SETTING: A tertiary referral paediatric hospital.
      SUBJECTS: A total of 31 (11 male, 20 female) children (aged 12.8+/-3.6 y) with CF
      and 32 (14 male, 18 female) healthy children without CF (aged 12.2+/-2.3 y) were
      enrolled in the short-term reproducibility study. Long-term REE measurement
      reproducibility was assessed in another 14 children (5 male, 9 female) with CF,
      comparing their initial REE measurement with a subsequent measurement 1-2 y
      later. METHODS: All children had measurements of height, weight, skinfold
      thickness and indirect calorimetry. RESULTS: There was no statistically
      significant difference in REE between repeated measurements in children with CF
      (mean+/-s.d., 6240+/-1280 and 6220+/-1315 kJ/24 h) and in the children without CF
      (6040+/-956 and 6015+/-943 kJ/24 h). For the children with CF, the intraclass
      correlation coefficient was 0.99 and for children without CF the intraclass
      correlation coefficient was 0.97. The measurement errors were 119 and 177 kJ,
      respectively. Approximately 80% of the variation in REE in the CF group and 70%
      in the group without CF was explained by fat-free mass (FFM). Analysis of the
      longitudinal CF data show there was no difference in REE between a child's first
      measurement (5140+/-1140 kJ) and their subsequent measurement (5460+/-1190 kJ),
      after adjustment for changes in body size between the measurements. CONCLUSION:
      This study has demonstrated that a short-term 20 min REE measurement is
      reproducible and therefore valid in children with CF and children without CF.
      These results also indicate that in children with CF, long-term REE measurements
      are reproducible.

PMID- 11593353
TI  - The development of waist circumference percentiles in British children aged 5.0
      16.9 y.
AB  - OBJECTIVE: To develop waist circumference percentile curves for British children
      and to compare these curves with those from other countries. DESIGN: Cross
      sectional study. SETTING: School-aged population. SUBJECTS: A representative
      sample of school children from the geographical regions of Great Britain,
      approximately in proportion to their age distribution. The sample population
      consisted of 8355 children (3585 males, 4770 females) with ages ranging between
      5.0 and 16.9 y. INTERVENTIONS: Waist circumferences were measured with a flexible
      non-elastic tape and waist circumference percentiles were constructed and
      smoothed using the LMS method. MAIN OUTCOME MEASURES: Smoothed waist
      circumference percentile curves. RESULTS: Mean waist circumference increased with
      age in both boys and girls. For girls, curves began to plateau after the age of
      13 y whereas, for boys, waist percentile curves continued to increase more
      sharply after this age. However, these curves mainly reflect the patterns of
      waist circumference in Caucasian children. CONCLUSIONS: These curves represent
      the first waist circumference percentiles for British children and could be used
      provisionally for both clinical and possibly epidemiological use, although they
      should be validated against equivalent longitudinal data. SPONSORSHIP: This
      project has been sponsored by UNL Diversity and Development Fund.

PMID- 11593354
TI  - The effect of replacing dietary saturated fat with polyunsaturated or
      monounsaturated fat on plasma lipids in free-living young adults.
AB  - OBJECTIVE: To examine, in free-living adults eating self-selected diets, the
      effects on plasma cholesterol of substituting saturated fat rich foods with
      either n-6 polyunsaturated or monounsaturated fat rich foods while at the same
      time adhering to a total fat intake of 30-33% of dietary energy. DESIGN: Two
      randomised crossover trials. SETTING: General community. SUBJECTS: Volunteer
      sample of healthy free-living nutrition students at the University of Otago.
      Trial I, n=29; and trial II, n=42. INTERVENTIONS: In trials I and II participants
      were asked to follow for 2(1/2) weeks a diet high in saturated fat yet with a
      total fat content that conformed to nutrition recommendations (30-33% energy).
      During the 2(1/2) week comparison diet, saturated fat rich foods were replaced
      with foods rich in n-6 polyunsaturated fats (trial I) whereas in trial II the
      replacement foods were rich in monounsaturated fats. Participants were asked to
      maintain a total fat intake of 30-33% of energy on all diets. MAIN OUTCOME
      MEASURES: Energy and nutrient intakes, plasma triglyceride fatty acids, and
      plasma cholesterol. RESULTS: When replacing saturated fat with either n-6
      polyunsaturated fat or monounsaturated fat, total fat intakes decreased by 2.9%
      energy and 5.1% energy, respectively. Replacing saturated fat with n-6
      polyunsaturated fat (trial I) lowered plasma total cholesterol by 19% [from 4.87
      (0.88) to 3.94 (0.92) mmol/l, mean (s.d.)], low density lipoprotein cholesterol
      by 22% [from 2.87 (0.75) to 2.24 (0.67) mmol/l], and high density lipoprotein
      cholesterol by 14% [from 1.39 (0.36) to 1.19 (0.34) mmol/l], whereas replacing
      saturated fat with monounsaturated fat (trial II) decreased total cholesterol by
      12%, low density lipoprotein cholesterol by 15%, and high density lipoprotein
      cholesterol by 4%, respectively. The change in the ratio of total to high density
      lipoprotein cholesterol was similar during trial I and trial II. CONCLUSIONS:
      Young adults are very responsive to dietary-induced changes in plasma cholesterol
      even when an isocaloric replacement of saturated fat with n-6 polyunsaturated or
      monounsaturated fat is not achieved. Replacing saturated fat with either n-6
      polyunsaturated or monounsaturated fat is equally efficacious at reducing the
      total to high density lipoprotein cholesterol ratio. SPONSORSHIP: University of
      Otago, Meadow Lea Ltd.

PMID- 11593355
TI  - Relation between arachidonic acid and docosahexaenoic acid in maternal and
      neonatal blood.

PMID- 11593356
TI  - Overexpression of human insulin-like growth factor-I promotes new tissue
      formation in an ex vivo model of articular chondrocyte transplantation.
AB  - Articular cartilage, the tissue that forms the gliding surface of joints, has a
      poor regenerative capacity. Insulin-like growth factor-I (IGF-I) is a polypeptide
      that is anabolic and mitogenic for cartilage. Transfection of articular
      chondrocytes with an expression plasmid vector containing the cDNA for human IGF
      I under the control of the cytomegalovirus promoter/enhancer led to expression of
      the transgene and synthesis of biologically relevant amounts of IGF-I protein.
      Transplantation of transfected articular chondrocytes on to the surface of
      articular cartilage explants led to the formation of a new tissue layer on the
      cartilage explant surface. The new tissue was characterized by the presence of
      type II collagen and proteoglycan and by the absence of type I collagen,
      consistent with hyaline-like cartilage. The tissue formed by the chondrocytes
      expressing IGF-I was thicker and contained more cells than controls transfected
      with an expression plasmid vector containing the Escherichia coli (E. coli) beta
      galactosidase (lacZ) gene. Transplantation of articular chondrocytes that
      overexpress human IGF-I also increased DNA synthesis and the synthesis of
      glycosaminoglycans by the underlying explant cartilage chondrocytes. These
      results identify a mechanism by which IGF-I may simultaneously promote
      chondrogenesis and shift cartilage homeostasis in an anabolic direction. The data
      further suggest that therapeutic growth factor gene transfer may be applicable to
      articular cartilage.

PMID- 11593357
TI  - Expression of HGF/NK4 in ovarian cancer cells suppresses intraperitoneal
      dissemination and extends host survival.
AB  - Peritoneal dissemination is the most frequent progression pathway of ovarian
      cancer and is therefore a key step to improve the prognosis. NK4, a large part of
      the alpha-chain of hepatocyte growth factor, is known to inhibit cancer cell
      migration. To characterize the function of NK4 and investigate its potential role
      in gene therapy of ovarian cancer, we introduced NK4 cDNA to an ovarian cancer
      cell line HRA and investigated its effects both in vitro and in vivo. HRA cells
      were transfected with either NK4 or luciferase-expression plasmids. After
      selection, NK4-expressing HRA cells (HRA/NK4) and the control cells (HRA/LUC)
      were obtained. NK4 was detected in the culture supernatant of HRA/NK4 by Western
      analysis. Migration capabilities of the cells were evaluated in vitro by scratch
      wound healing assay. The number of migrated cells was significantly smaller in
      the HRA/NK4 cultures than that in the control cultures (HRA or HRA/LUC). Also,
      the culture supernatant of HRA/NK4 significantly suppressed migration of control
      cells. This suppressive effect was observed when NK4-expressing cells were mixed
      with control cells at the ratio of 25% or more. In the in vivo experiments, HRA
      transfectants were injected intraperitoneally. The number of intraperitoneal
      tumors of HRA/NK4 was much smaller than that of control. In mice injected with
      HRA/NK4, ascites formation was suppressed and the survival was significantly
      prolonged. These findings suggest that NK4-mediated gene therapy can improve the
      prognosis of ovarian cancer by suppressing peritoneal dissemination.

PMID- 11593358
TI  - Organ distribution of gene expression after intravenous infusion of targeted and
      untargeted lentiviral vectors.
AB  - Lentiviral vectors represent an attractive technology platform from which to
      develop a targetable injectable gene delivery system for transduction of specific
      cell populations in vivo, irrespective of their cell cycle status. Targeted HIV-1
      based lentiviral vectors were generated by pseudotyping them with chimeric murine
      leukemia virus (MLV) envelope glycoproteins displaying N-terminal targeting
      polypeptides. Vectors displaying an EGF polypeptide were fully infectious on EGF
      receptor-negative cells, but were inactive on cells with abundant EGF receptors
      (inverse targeting). Receptor-mediated inactivation of gene transfer was overcome
      by competing the EGF receptors on the target cells with soluble EGF or by
      removing the displayed EGF domain from the surface of the vector particles by
      factor Xa cleavage of a specific protease substrate engineered into its tethering
      linker (protease targeting). Intravenous infusion of nontargeted HIV-1 vectors
      led to maximal luciferase activity in liver and spleen with moderate or minimal
      activity in heart, skeletal muscle, lung, brain, kidney, ovaries and bone marrow.
      In contrast, intravenous EGF-displaying vectors were expressed maximally in
      spleen with very low level luciferase expression detectable in liver (EGF
      receptor rich). Liver transduction by the EGF-displaying vector was restored by
      pretreating the animals with soluble EGF suggesting that these vectors are
      inversely targeted to spleen.

PMID- 11593359
TI  - Prediction and optimization of gene transfection and drug delivery by
      electroporation.
AB  - Although electroporation is widely used for laboratory gene transfection and
      gaining increased importance for nonviral gene therapy, it is generally employed
      using trial-and-error optimization schemes for lack of methods to predict
      electroporation's effects on cells. Therefore, we used a statistical approach to
      quantitatively predict molecular uptake and cell viability following
      electroporation and show that it predicts both in vitro and in vivo results for a
      wide range of molecules, including DNA, in 60 different cell types.
      Mechanistically, this broad predictive ability suggests that electroporation is
      mediated primarily by lipid bilayer structure and only secondarily by cell
      specific characteristics. For gene therapy applications, this approach should
      facilitate rational design of electroporation protocols.

PMID- 11593360
TI  - Systemic administration of naked plasmid encoding hepatocyte growth factor
      ameliorates chronic renal fibrosis in mice.
AB  - The progression of chronic renal diseases is considered as an irreversible
      process that eventually leads to end-stage renal failure characterized by
      extensive tissue fibrosis. At present, chronic renal fibrosis is incurable and
      the incidence of affected patients is on the rise worldwide. In this study, we
      demonstrate that delivery of hepatocyte growth factor (HGF) gene via systemic
      administration of naked plasmid vector markedly ameliorated renal fibrosis in an
      animal model of chronic renal disease induced by unilateral ureteral obstruction.
      A high level of exogenous HGF protein was detected in the obstructed kidneys
      following intravenous injection of naked plasmid encoding human HGF. Delivery of
      human HGF gene induced a sustained activation of extracellular signal-regulated
      kinases-1 and -2 in the obstructed kidneys. Exogenous HGF expression dramatically
      inhibited alpha-smooth muscle actin expression, attenuated renal interstitial
      accumulation and deposition of collagen I and fibronectin. In addition, exogenous
      HGF suppressed renal expression of pro-fibrogenic cytokine TGF-beta1 and its type
      I receptor in vivo. These results suggest that systemic administration of naked
      plasmid vector introduces a high level of exogenous HGF to the diseased kidneys,
      and that HGF gene transfer may provide a novel therapeutic strategy for
      amelioration of chronic renal fibrosis in vivo.

PMID- 11593361
TI  - Adenoviral vector-mediated insulin gene transfer in the mouse pancreas corrects
      streptozotocin-induced hyperglycemia.
AB  - Therapy for type 1 diabetes consists of tight blood glucose (BG) control to
      minimize complications. Current treatment relies on multiple insulin injections
      or an insulin pump placement, beta-cell or whole pancreas transplantation. All
      approaches have significant limitations and have led to the realization that
      novel treatment strategies are needed. Pancreatic acinar cells have features that
      make them a good target for insulin gene transfer. They are not subject to
      autoimmune attack, a problem with pancreas or islets transplantation, they are
      avidly transduced by recombinant adenoviral vectors, and capable of exporting a
      variety of peptides into the portal circulation. Recombinant adenoviral vectors
      were engineered to express either wild-type or furin-modified human insulin cDNA
      (AdCMVhInsM). Immunodeficient mice were made diabetic with streptozotocin and
      injected intrapancreatically with the vectors. BG and blood insulin levels have
      normalized after administration of AdCMVhInsM. Immunohistochemistry and electron
      microscopy showed the presence of insulin in acinar cells throughout the pancreas
      and localization of insulin molecules to acinar cell vesicles. The data clearly
      establish a relationship between intrapancreatic vector administration, decreased
      BG and elevated blood insulin levels. The findings support the use of pancreatic
      acinar cells to express and secrete insulin into the blood stream.

PMID- 11593362
TI  - Noninvasive, quantitative imaging in living animals of a mutant dopamine D2
      receptor reporter gene in which ligand binding is uncoupled from signal
      transduction.
AB  - The dopamine D2 receptor (D2R) has been used in adenoviral delivery systems and
      in tumor cell xenografts as an in vivo reporter gene. D2R reporter gene
      expression has been non-invasively, repetitively and quantitatively imaged by
      positron emission tomography (PET), following systemic injection of a positron
      labeled ligand (3-(2'-[18F]-fluoroethyl)-spiperone; FESP) and subsequent D2R
      dependent sequestration. However, dopamine binding to the D2R can modulate cyclic
      AMP levels. For optimal utilization of D2R as a reporter gene, it is important to
      uncouple ligand-binding from Gi-protein-mediated inhibition of cAMP production.
      Mutation of Asp80 or Ser194 produces D2Rs that still bind [3H]spiperone in
      transfected cells. The D2R80A mutation completely eliminates the ability of the
      D2R to suppress forskolin-stimulated cAMP accumulation in response to dopamine,
      in cells transfected with a D2R80A expression plasmid and in cells infected with
      replication-defective adenovirus expressing D2R80A. The D2R194A mutation
      substantially reduces, but does not completely eliminate, dopamine modulation of
      cAMP levels. Cultured cells infected with adenoviruses expressing D2R and D2R80A
      demonstrated equivalent [3H]spiperone binding activity. Moreover, hepatic FESP
      sequestration is equivalent, following intravenous injection of adenoviruses
      expressing D2R and D2R80A. The D2R80A mutant, which can no longer modulate cAMP
      levels following ligand binding, has full capability as a PET reporter gene.

PMID- 11593363
TI  - Adenovirus-mediated transfer of heme oxygenase-1 cDNA attenuates severe lung
      injury induced by the influenza virus in mice.
AB  - Heme oxygenase-1 (HO-1) is an inducible heat shock protein that regulates heme
      metabolism to form bilirubin, ferritin and carbon monoxide. Based on recent
      evidence that HO-1 is involved in the resolution of inflammation by modulating
      apoptotic cell death or cytokine expression, the present study examined whether
      overexpression of exogenous HO-1 gene transfer provides a therapeutic effect on a
      murine model of acute lung injury caused by the type A influenza virus. We
      demonstrate herein that the transfer of HO-1 cDNA resulted in (1) suppression of
      both pathological changes and intrapulmonary hemorrhage; (2) enhanced survival of
      animals; and (3) a decrease of inflammatory cells in the lung. TUNEL analysis
      revealed that HO-1 gene transfer reduced the number of respiratory epithelial
      cells with DNA damage, and caspase assay suggested that HO-1 suppressed lung
      injury via a caspase-8-mediated pathway. These findings suggest the feasibility
      of HO-1 gene transfer to treat lung injury induced by a pathogen commonly seen in
      the clinical setting. Since oxidative stress and lung injury are involved in many
      lung disorders, such as pneumonia induced by a variety of microorganisms and
      pulmonary fibrosis, HO-1 may be useful for wider clinical applications in gene
      therapy targeting lung disorders including acute pneumonia and pulmonary
      fibrosis.

PMID- 11593364
TI  - Highly efficient gene transfer into murine liver achieved by intravenous
      administration of naked Epstein-Barr virus (EBV)-based plasmid vectors.
AB  - Naked plasmid DNA (pDNA) injection could become an alternative procedure to viral
      and nonviral gene delivery systems. We have previously shown that Epstein-Barr
      virus (EBV)-based plasmid vectors containing the EBV nuclear antigen 1 (EBNA1)
      gene and the oriP sequence enable quite high and long-lasting expression in
      various in vitro and in vivo transfection systems. The EBV-based plasmids were
      intravenously injected into mice via their tail vein under high pressure. A large
      amount of the marker gene product was expressed in the liver; as much as 320
      microg of luciferase was demonstrated per gram of liver at 8 to 24 h after a
      single injection with 10 microg of DNA. More than 70% of liver cells stained with
      X-gal when beta-gal gene was transferred. The expression level was significantly
      higher than that obtained by conventional pDNA lacking the EBNA1 gene and oriP.
      On day 35 after the transfection, the expression from the EBV-based plasmid was
      approximately 100-fold stronger than the conventional pDNA gene expression. Both
      the EBNA1 gene and oriP are a prerequisite for the augmentation of the
      transfection efficiency. These results suggest that the intravascular
      transfection with naked EBV-based plasmid may provide a quite efficient, simple
      and convenient means to transduce therapeutic genes in vivo into the liver.

PMID- 11593366
TI  - Breastmilk: it's not just for breakfast anymore!

PMID- 11593367
TI  - A comparison of the safety of cupfeedings and bottlefeedings in premature infants
      whose mothers intend to breastfeed.
AB  - OBJECTIVE: To compare the safety of cupfeeding, an alternative feeding method, to
      bottlefeeding, the current standard of artificial feeding in the United States,
      in preterm infants whose mothers intend to breastfeed. STUDY DESIGN: In a
      prospective, randomized crossover study, 56 infants <or=34 weeks at birth, whose
      mothers indicated a desire to breastfeed, were studied. Skin-to-skin care and
      attempts at breast were encouraged frequently when babies were physiologically
      stable. When infants were >or=34 weeks' corrected gestational age, the order of
      the first two non-breast oral feedings was randomized by coin toss to one
      cupfeeding and one bottlefeeding. Trained Neonatal Intensive Care Unit nurses
      provided the feedings. Heart rate, respiratory rate, and oxygen saturation were
      recorded at 1-minute intervals for 10 minutes before and during the feeding.
      Volume taken, time required to complete the feed, and any apnea, bradycardia,
      choking, or spitting episodes were recorded. RESULTS: Heart rate (p<0.0001) and
      respiratory rate (p<0.0001) increased and oxygen saturation decreased (p=0.0002)
      during both cup and bottlefeedings compared to pre-feeding baselines. The amount
      of change in these three parameters from baseline to feeding period was similar
      for both feeding methods. The fraction of O(2) saturation <90% during baseline
      compared to the study period was different between these two feeding methods
      (p=0.02). There was a 10-fold increase in desaturations <90% during bottlefeeds
      compared to no change during cupfeeds. When comparing cupfeeding periods to
      bottlefeeding periods, heart rates were higher (p=0.009) and oxygen saturations
      lower (p=0.02) during bottlefeeds. There were no differences between methods in
      respiratory rate, choking, spitting or apnea, and bradycardia. Volumes taken were
      lower (p=0.001) and duration of feeds longer (p=0.002) during cupfeedings.
      CONCLUSION: During cupfeedings, premature infants are more physiologically
      stable, with lower heart rates, higher oxygen saturations, and less
      desaturations, than during bottlefeedings. However, cupfed infants took less
      volume, over more time, than bottlefed for these initial feedings. Based on
      better physiologic stability and no difference in untoward effects, cupfeeding is
      at least as safe, if not safer, than bottlefeeding in this population. This study
      supports the use of cupfeeding as a safe alternative feeding method for premature
      infants learning to breastfeed.

PMID- 11593368
TI  - Association of human milk feedings with a reduction in retinopathy of prematurity
      among very low birthweight infants.
AB  - INTRODUCTION: With the increased survival of very low birthweight (VLBW) infants,
      weighing less than 1500 g at birth, the incidence of retinopathy of prematurity
      (ROP), a significant cause of blindness among children in the United States, is
      also increasing. Preterm infants with a positive diagnosis of ROP during the
      perinatal period are at increased risk for ocular abnormalities and for deficits
      in visual function during later periods of development. Human milk has many
      antioxidant constituents including inositol, vitamin E, and beta-carotene that
      may protect against the development of ROP. OBJECTIVE: The objective of this
      study was to examine the effect of human milk feedings on the incidence of ROP
      among VLBW infants. STUDY DESIGN: Observational cohort study. PARTICIPANTS: We
      identified 283 VLBW infants admitted to the Georgetown University Medical Center
      Neonatal Intensive Care Unit (NICU) from January 1992 through September 1993. All
      infants surviving to receive enteral feeding and ophthalmologic examinations for
      ROP (n=174) were included in the analysis. METHODS: Type of feeding (human milk
      versus exclusive formula), presence of ROP, and potential confounding variables
      were abstracted retrospectively from medical records. ROP was present if any
      stage of ROP was diagnosed at any age during the initial NICU hospitalization;
      each case was counted once based on the worse severity of ROP in either eye.
      Multiple logistic regression was used to control for confounders. MAIN OUTCOME
      MEASURE: ROP. RESULTS: Major predictors of ROP were similar in both feeding
      groups including gestational age, days on mechanical ventilation, and total
      number of days on supplemental oxygen. The incidence of ROP differed
      significantly by type of feeding (human milk -41.0% vs. formula -63.5%, p=0.005).
      Human milk feeding independently correlated with a reduced odds of ROP (OR: 0.42,
      95% CI: 0.19 to 0.93) (p=0.03), controlling for gestational age, duration of
      supplemental oxygen therapy, 5-minute Apgar score, and race. Human milk feeding
      independently correlated with a reduced odds of ROP (OR: 0.46, 95% CI: 0.18 to
      0.91) (p=0.03), controlling for birthweight, duration of supplemental oxygen
      therapy, 5-minute Apgar score, and race. CONCLUSION: Human milk feeding among
      VLBW infants was associated with a lower incidence of ROP compared to exclusively
      formula-fed VLBW infants after adjusting for confounding variables.

PMID- 11593369
TI  - Reduction of donor exposures in premature infants by the use of designated
      adenine-saline preserved split red blood cell packs.
AB  - OBJECTIVE: Critically ill neonates frequently require multiple small volume red
      blood cell (RBC) transfusions. RBC units assigned to individual infants, used
      sequentially in small aliquots until the original expiration date, can
      substantially reduce donor exposures. In 1993, adenine-saline solution (AS-3) was
      introduced by the Canadian Red Cross as the red cell storage medium to replace
      citrate-phosphate-dextrose-adenine anticoagulant-preservative solution (CPDA-1).
      We surveyed the safety and efficacy of using AS-3 split packs, stored up to 35
      days, for premature infants. STUDY DESIGN: Units of packed cells were aseptically
      welded to three satellite bags using a sterile connecting device. When blood was
      requested for a small volume transfusion, the first satellite bag was used and
      the others were set aside for the same baby, for use up until their expiration
      date of 35 days. RESULTS: Over a 1-year period, 56 infants received a total of
      263 AS-3 transfusions from 97 donors, with a mean of 4.7 transfusions and 1.7
      donor exposures per infant. Following a 7-ml/kg RBC transfusion, mean rise in
      hematocrit (hct) was 0.04, regardless of the age of the unit, mean change in
      serum potassium was -0.16 mmol/l and mean change in total bilirubin was +1.86
      micromol/l. The posttransfusion hct was not reduced with the use of the older red
      cell packs. CONCLUSION: Designated AS-3-preserved split RBC packs effectively
      limit donor exposures, can safely be used for neonatal small volume transfusions,
      and give a constant transfusion effect after up to 35 days of storage.

PMID- 11593370
TI  - The relationship between hematocrit and bleeding time in very low birth weight
      infants during the first week of life.
AB  - OBJECTIVES: The bleeding time is a measurement of platelet and capillary
      interaction following a small standardized cutaneous incision. In adults, anemia
      causes a prolongation of the bleeding time, and we hypothesized that the same
      would be true in very low birth weight (VLBW) infants during their first week of
      life. STUDY DESIGN: Template bleeding times, using the Surgicutt Newborn device,
      were performed on 20 VLBW weight infants <or=7 days old, before, and again
      following a clinically ordered erythrocyte transfusion. RESULTS: Neonates who had
      pretransfusion hematocrits <or=0.28 l/l had longer bleeding times, which fell
      164+/-25 seconds (mean+/-SD; p<0.0001) following transfusion. Patients with
      pretransfusion hematocrits >0.28 l/l had no significant reduction in bleeding
      time following transfusion. CONCLUSIONS: In VLBW infants, during their first week
      of life (the time when their risk of intraventricular hemorrhage is greatest), a
      low hematocrit is associated with a significant prolongation in the bleeding
      time.

PMID- 11593371
TI  - The effects of intrauterine cocaine exposure on the respiratory status of the
      very low birth weight infant.
AB  - OBJECTIVES: This study examined the effects of intrauterine cocaine exposure on
      very low birth weight infants with respect to their surfactant requirement and
      need for ventilatory support. STUDY DESIGN: A retrospective cohort study was
      conducted on infants with birth weight between 750 and 1500 g admitted to the
      neonatal intensive care unit between January 1992 and January 1995. RESULTS: Of
      the 149 infants studied, 48 infants were exposed only to cocaine and 101 infants
      had no drug exposure. There were no significant differences between the two
      groups for gestational age, sex, abruptio placenta, prolonged rupture of
      membranes, and antenatal steroid usage. The cocaine-exposed group had a
      significantly greater birth weight (1190 vs. 1109, p<0.02), less prenatal care
      (48% vs. 14%, p<0.00007), older maternal age (30 vs. 24, p<0.00002), more black
      race (79% vs. 57%, p<0.01), and more rapid plasma reagin (RPR) positivity (25%
      vs. 2%, p<0.00006). There were no significant differences in median APGAR scores,
      or incidence of necrotizing enterocolitis, retinopathy of prematurity (ROP),
      intraventricular hemorrhage (IVH), and bronchopulmonary dysplasia (BPD) between
      the two groups. Cocaine-exposed infants received surfactant treatment less often
      (73% vs. 48%, p<0.0035), received fewer mean doses of surfactant (0.4 vs. 10.0,
      p<0.0014), and were intubated less frequently (44% vs. 65%, p<0.012). There was
      no significant difference between groups for intubation at 24 and 48 hours and
      for the development of bronchopulmonary dysplasia. CONCLUSION: Perinatal cocaine
      exposure appears to have some significant short-term effects on the need for
      surfactant replacement therapy and need for initial intubation in respiratory
      distress syndrome (RDS) but no overall effect on the development of BPD.

PMID- 11593372
TI  - Purulence and gram-negative bacilli in tracheal aspirates of mechanically
      ventilated very low birth weight infants.
AB  - OBJECTIVE: Tracheal aspirates (TAs) from mechanically ventilated very low birth
      weight (VLBW) infants are frequently obtained during the evaluation of suspected
      sepsis, tracheitis, or ventilator-associated pneumonia (VAP). Purulence and
      bacteria in Gram stain of bronchopulmonary secretions are considered signs of
      respiratory infection, and medical decisions are made on the assumption that they
      are predictors of positive bacterial tracheal cultures (TCs). The purpose of this
      retrospective investigation was to establish the relationship of purulence and
      bacteria in TA from ventilated VLBW infants with positive TC and to identify its
      clinical significance. STUDY DESIGN: One hundred and seventy consecutively born
      VLBW infants (1996 to 1998) who remained on mechanical ventilation longer than 1
      week were studied. Demographic, laboratory, and clinical data were obtained from
      hospital medical records. Purulence, defined by the number of polymorphonuclear
      leukocytes (PMNs) per low power field (LPF), was reported as light (<25 PMNs/LPF)
      or moderate/heavy (>or=25 PMNs/LPF) for every TA. RESULTS: Purulence was absent
      in 469 of 646 (72%) TA taken from 170 infants. Light purulence was present in 17%
      and moderate/heavy purulence in 11%. TCs were positive in 58% of non-purulent,
      94% of light, and 100% of moderate/heavy purulent TA. Bacteria on Gram stain were
      present in 12% of non-purulent, 70% of light purulent, and 83% of moderate/heavy
      purulent TA. Moderate/heavy purulence in TA was predictive of a positive TC with
      Gram-negative bacilli (GNB) with 70% sensitivity, 100% specificity, 100% positive
      predictive value, and 67% negative predictive value. Purulence in TA, as well as
      GNB airway colonization, became more frequent as mechanical ventilation
      progressed and was not associated with a particular GNB species. There were 79
      infants who never had purulent TA and 91 who, at some time during the
      hospitalization, did. At the time of first purulent TA, 65 (71%) of 91 infants
      were asymptomatic. Twenty-six infants (29%) had clinical deterioration for which
      they underwent sepsis work-up. Three had blood stream infection, 5 VAP, 5
      tracheitis, and 13 respiratory complications of non-infectious etiology. Four of
      five VAP infants died; all others survived. CONCLUSION: In VLBW infants,
      purulence in TA is associated with prolonged endotracheal intubation and is
      temporally related to GNB airway colonization. At the time of the first purulent
      TA, the majority of mechanically ventilated VLBW infants are asymptomatic. Only a
      few symptomatic VLBW infants had nosocomial respiratory infection. Understanding
      the clinical significance of purulence and GNB in TA from this unique patient
      population is important for management and prognosis, and it may decrease concern
      for infection and the associated use of antibiotics.

PMID- 11593373
TI  - Rapid spectrophotometric measurements of total bilirubin in intact and hemolyzed
      neonatal blood: a feasibility study.
AB  - BACKGROUND: Conventional methods for measuring the total bilirubin concentration
      in blood require the use of serum or plasma, but physically separating red blood
      cells from plasma by centrifugation is a time-consuming and potentially dangerous
      process that does not lend itself to rapid, near-patient testing. Therefore, we
      have sought to determine whether spectrophotometric measurements of total
      bilirubin concentration are feasible in unaltered whole blood. METHODS: We
      modified an Hb-Quick hemoglobinometer (Avox Systems, Inc., San Antonio, TX), a
      relatively new, portable, battery-powered instrument that uses disposable
      cuvettes and a reagentless system to measure total hemoglobin in nonhemolyzed,
      whole blood. The prototype consisted of an Hb-Quick equipped with light-emitting
      diodes with emissions at five different wavelengths to measure total bilirubin
      and total hemoglobin. Using blood samples from neonates with suspected
      hyperbilirubinemia, we made measurements on plasma from centrifuged samples and
      on hemolyzed and nonhemolyzed aliquots of the same blood samples. RESULTS: In the
      first series of experiments, we compared the Unistat bilirubinometer's readings
      with the prototype's measurements of bilirubin in plasma. There was a close
      linear correlation between the prototype's measurements and those of the
      reference instrument (slope=1.01, r(2)=0.991). Subsequently, we used the
      prototype's measurements on plasma as the reference method and compared them with
      readings on hemolyzed and nonhemolyzed aliquots of each sample. Readings on
      hemolyzed and nonhemolyzed aliquots were significantly correlated with the
      measurements in plasma, but the regression lines did not have a slope of 1.
      However, when the measurements on hemolyzed and nonhemolyzed blood were scaled
      appropriately to compensate for the fact that red cells "dilute" the bilirubin in
      plasma, the correlation coefficients improved, and there was then a 1:1
      relationship between the measurements in whole blood and plasma. CONCLUSIONS:
      These preliminary findings demonstrate the feasibility of developing a portable
      instrument to measure total bilirubin in unaltered whole blood. The advantages of
      this method are speed, elimination of centrifugation or other sample preparation,
      and instrument portability. The disadvantage is that the concentration units are
      unconventional, i.e., milligrams of bilirubin per volume of whole blood. However,
      the instrument can be programmed to display the total bilirubin concentration in
      traditional units, e.g., milligrams of bilirubin per volume of plasma.

PMID- 11593374
TI  - Evaluation of the effectiveness of the standardized neonatal resuscitation
      program.
AB  - OBJECTIVE: To determine if health care personnel trained in the Neonatal
      Resuscitation Program (NRP) used the NRP guidelines in the resuscitation of
      newborn babies. To determine differences between self-reporting and documentation
      of resuscitation in medical records. STUDY DESIGN: Using a validated
      questionnaire, individuals participating in resuscitation of newborns voluntarily
      phoned and answered questions on an Interactive Voice Response (IVR) system. The
      study was undertaken in level II hospitals in Southern Alberta with 7500
      deliveries per year. RESULTS: Of the 5155 babies delivered during the study, 16%
      required resuscitation (bag and mask ventilation 10.6%, intubation for meconium
      or intermittent positive pressure ventilation, IPPV, 3.6%, cardiac massage, CM,
      0.3%, epinephrine 0.1%, naloxone 6.9%). Of babies whose interventions could be
      assessed, bag and mask was correct in 99%, endotracheal intubation for IPPV in
      100%, and CM in 100%. Only 75% of babies had meconium managed correctly and 92%
      had naloxone administered according to guidelines. There were more instances
      where IVR (48) reported a procedure, which was not charted versus charted and not
      reported by IVR (21). Educational needs identified by IVR included skills of
      resuscitation and NRP indications for management. CONCLUSION: Bag and mask
      ventilation and intubation for neonatal resuscitation are more common than
      previously reported. Management of the meconium-stained baby and use of naloxone
      require further education. Compared to charts, use of IVR system allows more
      complete documentation with rationale of interventions and identification of
      continuing educational needs.

PMID- 11593375
TI  - ROP--forme fruste.

PMID- 11593376
TI  - Mechanical ventilation during pregnancy using a helium-oxygen mixture in a
      patient with respiratory failure due to status asthmaticus.
AB  - The authors present a 15-year-old with a second trimester intrauterine pregnancy
      who developed respiratory failure as the result of status asthmaticus and the
      development of the adult respiratory distress syndrome. Mechanical ventilation
      was provided with a combination of oxygen and helium to facilitate gas exchange
      and limit peak inflating pressures. The physiologic basis for helium's potential
      beneficial effects on gas exchange are reviewed. Previous reports concerning the
      use of helium during mechanical ventilation as well as the techniques of delivery
      are discussed.

PMID- 11593377
TI  - Disseminated Bipolaris spicifera in a neonate.
AB  - We report a premature infant with disseminated fungal infection identified as
      Bipolaris spicifera. The infant was born at 23 4/7 weeks' gestation, weighing 780
      g. At day of life (DOL) 7 erythematous areas on the back were noticed that
      progressed to black, necrotic skin lesions. A shave biopsy showed invasive fungal
      organisms that were identified by culture as B. spicifera. The lesions progressed
      despite aggressive surgical debridement and antifungal therapy. On autopsy,
      fungal organisms found throughout the internal organs confirmed disseminated
      disease with B. spicifera. This organism is now more often recognized as a human
      pathogen; however, this is the first reported case in a neonate.

PMID- 11593378
TI  - Can congenital CMV infection lead to intracranial hemorrhage?

PMID- 11593379
TI  - Bilateral thalamic lesions in a newborn with intrauterine asphyxia after maternal
      cardiac arrest--a case report with literature review.
AB  - Hypoxic-ischemic brain damage in preterm and term infants is one major cause of
      neonatal neurologic morbidity. Depending on the gestational age and the extent of
      hypoxia, different pathologic findings have been observed. Hypoxic-ischemic
      lesion of the thalamus is the least common form of cerebral injury. Although long
      term outcome with spastic or extrapyramidal cerebral palsy is known, clinical
      features in the neonatal period are not well described. We report an infant with
      bilateral hypoxic-ischemic thalamic lesions after maternal cardiac arrest at 28
      weeks of gestation. Clinical features and diagnostic results of our patient are
      compared to information given in the literature to define the clinical entity of
      hypoxic-ischemic thalamic lesions in neonates better.

PMID- 11593380
TI  - Mycotic pseudoaneurysm of abdominal aorta in premature infant.

PMID- 11593381
TI  - Diaphragmatic hernia with homolateral limb reduction.

PMID- 11593383
TI  - Dephosphorylated hypoxia-inducible factor 1alpha as a mediator of p53-dependent
      apoptosis during hypoxia.
AB  - Under hypoxia, HIF-1alpha binds to aryl hydrocarbon receptor nuclear translocator
      (ARNT, also called HIF-1beta) to activate expression of genes important for cell
      survival. Alternatively, HIF-1alpha can bind to the tumor suppressor p53 and
      promote p53-dependent apoptosis. Here we show that the opposite functions of HIF
      1alpha are distinguished by its phosphorylation status. Two distinguishable forms
      of HIF-1alpha, phosphorylated and dephosphorylated, were induced during hypoxia
      induced apoptosis. The phosphorylated HIF-1alpha was the major form that bound to
      ARNT. Ectopically expressed ARNT was consistently able to enhance HIF-1alpha
      phosphorylation in a binding-dependent manner. In contrast, the dephosphorylated
      HIF-1alpha was the major form that bound to p53. Depletion of the
      dephosphorylated HIF-1alpha, by using the Hsp90 inhibitor geldanamycin A that had
      little effect on the phosphorylated HIF-1alpha expression, suppressed p53
      induction and subsequent apoptosis. Depletion of dephosphorylated HIF-1alpha also
      prevented hypoxia-induced nuclear accumulation of HDM2, a negative regulator of
      p53. Our results indicate that the functions of HIF-1alpha varied with its
      phosphorylation status and that dephosphorylated HIF-1alpha mediated apoptosis by
      binding to and stabilizing p53.

PMID- 11593384
TI  - Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells.
AB  - FasL and TNF-related apoptosis-inducing ligand (TRAIL) belong to a subgroup of
      the TNF superfamily which induce apoptosis by binding to their death domain
      containing receptors. In the present study we have utilized a panel of seven cell
      lines derived from human malignant gliomas to characterize molecular pathways
      through which FasL and TRAIL induce apoptosis in sensitive glioma cells and the
      mechanisms of resistance in cell lines which survive the death stimuli. Our
      findings indicate that FADD and Caspase-8 are essential for FasL and TRAIL
      mediated apoptosis in glioma cells. One sensitive cell line (D270) can be
      protected from FasL and TRAIL induced death by anti-apoptotic Bcl-2 family
      members while another (D645) cannot, implying that these lines may represent
      glioma examples of type II and type I cells respectively. For the first time we
      demonstrate resistance to FasL but not to TRAIL within the one glioma cell line.
      Furthermore, we report distinct mechanisms of resistance within different glioma
      lines, including downregulation of Caspase-8 in U373MG. Cycloheximide sensitized
      four of the resistant cell lines suggesting the presence of labile inhibitors.
      None of the known apoptosis inhibitors examined accounted for the observed
      resistance, suggesting novel inhibitors may exist in glioma cells.

PMID- 11593385
TI  - The anti-apoptotic role of interleukin-6 in human cervical cancer is mediated by
      up-regulation of Mcl-1 through a PI 3-K/Akt pathway.
AB  - Interleukin-6 (IL-6), a multifunctional cytokine, has recently been implicated in
      human cervical cancer, though the mechanism remains elusive. This study
      demonstrates that the anti-apoptotic protein Mcl-1 and IL-6 was concomitantly
      expressed in human cervical cancer tissues and cell lines, but not in normal
      cervix tissues. Upon IL-6 treatment, Mcl-1, but not other Bcl-2 family members,
      was rapidly up-regulated peaking at 4-8 h in human cervical cancer C33A cells.
      Supporting this observation, using anti-IL-6 or anti-IL-6 receptor antibody to
      interrupt the IL-6 autocrine loop in SiHa cells significantly reduced cellular
      level of Mcl-1. This study hypothesizes that the expression of Mcl-1 in cervical
      cancer cells is regulated by IL-6. The matter of which signaling pathways
      transduced by IL-6 is responsible for the Mcl-1 up-regulation is further
      investigated herein. Blocking the STAT3 or MAPK pathway with dominant-negative
      mutant STAT3F or the MEK inhibitor PD98059 failed to inhibit IL-6-mediated Mcl-1
      expression. Meanwhile, the IL-6-induced Mcl-1 up-regulation was effectively
      abolished by treatment with PI 3-K inhibitors, LY294002. Additionally,
      overexpression of dominant-negative (dn) Akt in C33A cells could inhibit the IL-6
      induced increase of Mcl-1. Finally, overexpression of IL-6 in C33A cells caused a
      markable resistance to apoptosis induced by doxorubicin or cisplatin. Transient
      transfection of IL-6-overexpressed cells with a mcl-1 antisense vector, leading
      to the attenuation of their apoptosis-resistant activity. In conclusion, the data
      herein suggest that IL-6 regulated the mcl-1 expression via a PI 3-K/Akt
      dependent pathway that may facilitate the oncogenesis of human cervical cancer by
      modulating the apoptosis threshold.

PMID- 11593386
TI  - WNT pathway and mammary carcinogenesis: loss of expression of candidate tumor
      suppressor gene SFRP1 in most invasive carcinomas except of the medullary type.
AB  - Secreted Frizzled-related protein 1 (SFRP1) encodes a member of a protein family
      that contains a cysteine-rich domain similar to the WNT-binding site of Frizzled
      receptors and regulates the WNT pathway. The WNT pathway is frequently altered in
      human cancers. We have defined the pattern of SFRP1 mRNA expression in the
      progression of breast cancer. We show that SFRP1 is expressed in the epithelial
      component of normal breast, in the in situ component of ductal carcinomas and is
      lost in more than 80% of invasive breast carcinomas except the medullary type.
      Loss of SFRP1 expression is correlated with the presence of hormonal receptors.
      Conversely, the maintenance of SFRP1 in carcinomas is correlated with the
      presence of lymphoplasmocytic stroma. No significant association was observed
      between SFRP1 status and the level of apoptosis in tumoral cells.

PMID- 11593387
TI  - p53 and its homologues, p63 and p73, induce a replicative senescence through
      inactivation of NF-Y transcription factor.
AB  - Recent studies have identified two p53 homologues, p63 and p73. They activate p53
      responsive promoters and induce apoptosis when overexpressed in certain human
      tumors. Here, we report that p63, like p53 and p73, induces replicative
      senescence when expressed in a tetracycline-regulated manner in EJ cells lacking
      a functional p53. In addition to transcription activation of p53-responsive
      genes, we found that p63 and p73 repress transcription of the cdk1 and cyclin B
      genes, both of which are irreversibly repressed in senescent human fibroblast. In
      transient transfection assay, p63 and p73 repress the cdk1 promoter regardless of
      the presence of a dominant negative mutant form of p53. Furthermore, we found
      that DNA binding activity of NF-Y transcription factor, which is essential for
      transcription of the cdk1 and cyclin B genes and inactivated in senescent
      fibroblast, is significantly decreased by expression of either of p53, p63, or
      p73. Since NF-Y binds to many promoters besides the cdk1 and cyclin B promoters,
      inactivation of NF-Y by p53 family genes may be a general mechanism for
      transcription repression in replicative senescence.

PMID- 11593388
TI  - Cooperative and redundant effects of STAT5 and Ras signaling in BCR/ABL
      transformed hematopoietic cells.
AB  - The Akt, Ras and STAT5 signaling pathways have each been linked to transformation
      of hematopoietic cells by BCR/ABL. However the relative contributions of these
      signaling pathways to BCR/ABL mediated cytokine-independent survival,
      proliferation and resistance to DNA damage-induced apoptosis have not been
      systematically defined. Here we report that activation of either Akt, Ras or
      STAT5 confers cytokine-independent survival to IL-3 dependent BaF3 cells. Ras or
      STAT5, but not Akt, also drives cytokine-independent proliferation and imparts
      sustained resistance to DNA damage-induced apoptosis. We also show that dominant
      negative (DN) inhibition of STAT5, but not Ras or Akt, significantly reduces
      resistance to DNA damage-induced apoptosis in BCR/ABL transformed BaF3 cells.
      Whereas inhibition of STAT5 or Ras alone does not compromise cytokine-independent
      proliferation of BaF3-BCR/ABL cells, simultaneous blockade of both STAT5 and Ras
      reduces proliferation and maximally sensitizes BaF3-BCR/ABL cells to DNA damage
      induced by gamma-irradiation, suggesting a cooperative role for these two
      signaling pathways in BCR/ABL transformation. The anti-apoptotic properties of
      BCR/ABL can be partly explained by an increase in the expression of Pim-1 and Bcl
      XL, as ectopic expression of these STAT5 target genes imparts both cytokine
      independent survival and partial gamma-radiation resistance. These data
      illustrate both cooperative and redundant effects of STAT5 and Ras signaling in
      BCR/ABL transformed cells, with STAT5 playing a dominant role in resistance to
      DNA damage-induced apoptosis.

PMID- 11593389
TI  - Activation of the interferon-inducible protein kinase PKR by hepatocellular
      carcinoma derived-hepatitis C virus core protein.
AB  - Hepatitis C virus (HCV) is a major etiological agent of chronic liver disease and
      hepatocellular carcinoma (HCC). We demonstrate herewith that HCV core proteins
      encoded by sequences isolated from HCC tumor tissues, but not those derived from
      their non-tumor counterparts in the same liver, co-localise in vitro and in vivo
      and co-immunoprecipitate with PKR in hepatocytic Huh7 cells. We show that this
      association in fact augments the autophosphorylation of PKR and the
      phosphorylation of the translation initiation factor eIF2alpha, which are two
      markers of PKR activity. The present study therefore identifies a novel model of
      virus-cell interactions whereby a viral protein, the HCV core, activates PKR
      activity.

PMID- 11593390
TI  - Nrh, a human homologue of Nr-13 associates with Bcl-Xs and is an inhibitor of
      apoptosis.
AB  - In search of human homologues of the anti-apoptotic protein Nr-13, we have
      characterized a human EST clone that potentially encodes a protein, which is the
      closest homologue of Nr-13 among the Bcl-2 family members, to date known, in
      humans. Phylogenetic analyses suggest Human nrh, Mouse diva/boo and Quail nr-13
      to be orthologous genes. The nrh gene has the same overall organization as nr-13
      and diva/boo with one single intron interrupting the ORF at the level of the Bcl
      2-homology domain BH2. RT-PCR-based analysis of nrh expression indicated that
      this gene is preferentially expressed in the lungs, the liver and the kidneys.
      Interestingly, two in frame ATG codons can lead potentially to the synthesis of
      two products, one of them lacking 10 aminoacids at the N-terminal end. Sequence
      alignment with Nr-13 and Diva/Boo in addition to secondary structure prediction
      of the nrh transcript suggested that the shortest protein will be preferentially
      synthetized. Immunohistochemical analyses have revealed that Nrh is associated
      with mitochondria and the nuclear envelope. Moreover, Nrh preferentially
      associates with the apoptosis accelerator Bcl-Xs and behaves as an inhibitor of
      apoptosis both in yeast and vertebrate cells.

PMID- 11593391
TI  - Defects in transcription coupled repair interfere with expression of p90(MDM2) in
      response to ultraviolet light.
AB  - Ultraviolet (UV) irradiation transiently stabilizes p53 through a mechanism that
      may require a decrease in the activity of the ubiquitin ligase, p90(MDM2).
      Conversely, the recovery of low levels of p53 following UV exposure may depend on
      an increase in p90(MDM2). The level of p90(MDM2) is increased by UV light
      following the p53-dependent induction of an internal mdm2 promoter, P2. If this
      induction of mdm2 were critical for the recovery of low levels of p53 following
      UV exposure, defects in mdm2's transcription would result in a prolonged increase
      in p53. Cells defective in transcription coupled repair (TCR) maintain high
      levels of p53 for a prolonged period following UV exposure. Such cells also have
      defects in general transcription after UV irradiation. We investigated whether
      TCR-deficient cells express diminished levels of mdm2 mRNA and p90(MDM2)
      following UV exposure. We found that transcription of mdm2 was reduced in TCR
      deficient cells. The uninducible mdm2 promoter, P1, was more sensitive to the
      inhibitory effects of UV irradiation than the P2 promoter. The decrease in
      transcription from the P1 promoter was sufficient to reduce the level of
      p90(MDM2) and correlated with a prolonged increase in p53. Thus, p53-independent
      transcription of mdm2 appears critical to p53's regulation.

PMID- 11593392
TI  - Sensitization for death receptor- or drug-induced apoptosis by re-expression of
      caspase-8 through demethylation or gene transfer.
AB  - Resistance of tumors to treatment with cytotoxic drugs, irradiation or
      immunotherapy may be due to disrupted apoptosis programs. Here, we report in a
      variety of different tumor cells including Ewing tumor, neuroblastoma, malignant
      brain tumors and melanoma that caspase-8 expression acts as a key determinant of
      sensitivity for apoptosis induced by death-inducing ligands or cytotoxic drugs.
      In tumor cell lines resistant to TRAIL, anti-CD95 or TNFalpha, caspase-8 protein
      and mRNA expression was decreased or absent without caspase-8 gene loss.
      Methylation-specific PCR revealed hypermethylation of caspase-8 regulatory
      sequences in cells with impaired caspase-8 expression. Treatment with the
      demethylation agent 5-Aza-2'-deoxycytidine (5-dAzaC) reversed hypermethylation of
      caspase-8 resulting in restoration of caspase-8 expression and recruitment and
      activation of caspase-8 at the CD95 DISC upon receptor cross-linking thereby
      sensitizing for death receptor-, and importantly, also for drug-induced
      apoptosis. Inhibition of caspase-8 activity also inhibited apoptosis
      sensitization by 5-dAzaC. Similar to demethylation, introduction of caspase-8 by
      gene transfer sensitized for apoptosis induction. Hypermethylation of caspase-8
      was linked to reduced caspase-8 expression in different tumor cell lines in vitro
      and, most importantly, also in primary tumor samples. Thus, these findings
      indicate that re-expression of caspase-8, e.g. by demethylation or caspase-8 gene
      transfer, might be an effective strategy to restore sensitivity for chemotherapy-
      or death receptor-induced apoptosis in various tumors in vivo.

PMID- 11593393
TI  - Induction of FGF receptor 2-IIIb expression and response to its ligands in
      epithelial ovarian cancer.
AB  - Epithelial ovarian cancers (EOCs) arise in the Ovarian Surface Epithelium (OSE).
      This tissue is a simple, poorly committed mesothelium which exhibits
      characteristics of epithelial and mesenchymal cells when grown in culture. In
      contrast, EOCs frequently exhibit properties of complex epithelial tissues of the
      female reproductive tract, such as oviductal, endometrial and cervical epithelia,
      and show induction of expression of epithelial markers such as E-cadherin.
      Fibroblast Growth Factor Receptor 2 isoform IIIb (FGF receptor 2-IIIb) is a
      spliced variant of FGF receptor 2 that binds the ligands FGF-1 and FGF-7 with
      high affinity, and is expressed exclusively by epithelial cells. We have studied
      the expression of FGF receptor 2-IIIb and its ligands in primary cultures of
      normal human OSE, EOC cell lines and snap frozen tissue from EOCs. Expression of
      FGF receptor 2-IIIb mRNA is undetectable in normal OSE, but is expressed in 16/20
      (80%) of EOCs. FGFs 1 and 7 mRNAs are expressed in normal OSE, whilst only 4/20
      (20%) and 12/20 (60%) of EOCs demonstrated expression for these ligands
      respectively. However, FGF-7 protein was detected in 70% (mean level=0.7 ng/ml)
      of ascitic fluids obtained from patients with EOC. FGFs 1 and 7 stimulate DNA
      synthesis in EOC cell lines that express FGF receptor 2-IIIb. Moreover, DNA
      synthesis in these cell lines can be partially blocked by blocking antisera to
      FGFs 1 and 7. It is suggested that induction of expression of FGF receptor 2-IIIb
      may play a role in the development of EOCs by rendering the OSE susceptible to
      paracrine and/or autocrine stimulation by its requisite FGF ligands.

PMID- 11593394
TI  - Ectopic expression of Cdk6 circumvents transforming growth factor-beta mediated
      growth inhibition.
AB  - Transforming growth factor-beta (TGF-beta) induced growth arrest of cells
      involves regulation of the activities of both D- and E-type cyclin kinase
      complexes thought to be mediated primarily by the regulation of p15(Ink4b) and
      p27(Kip1) cyclin kinase inhibitors. We show here that TGF-beta downregulates Cdk6
      and that transient and stable expression of Cdk6 in Mv1Lu mink epithelial cells
      overrides TGF-beta mediated arrest. The main effect of the ectopic Cdk6
      expression was to sequester TGF-beta induced p15(Ink4b) and to maintain more
      p27(Kip1) in cyclin D-complexes preventing the complete shift of p27(Kip1) to
      Cdk2 invoked by TGF-beta. This led to the presence of an active cyclinD-Cdk6
      p27(Kip1) complex and partially active cyclin E-Cdk2 complex and resulted in the
      failure of TGF-beta to fully arrest Mv1Lu cell growth. Though dominant negative
      Cdk6, expressed similarly in the cells, sequestered both p15(Ink4b) and
      p27(Kip1), it lacks kinase activity and was unable to override the TGF-beta
      arrest. The results demonstrate that downregulation of Cdk6 kinase is required
      for the enforcement of the G(1)-phase arrest by TGF-beta and results in changes
      in association of the p15(Ink4b) and p27(Kip1) inhibitors with D- and E-type
      cyclin kinase complexes.

PMID- 11593395
TI  - Chk2 tumour suppressor protein in human spermatogenesis and testicular germ-cell
      tumours.
AB  - Chk2 is a transducer of DNA damage signals and a tumour suppressor whose germ
      line mutations predispose to diverse tumour types. Unlike its downstream targets
      such as the p53 tumour suppressor, the expression patterns of Chk2 in tissues and
      tumours remain unknown. As DNA breaks occur commonly during gametogenesis, and
      p53 is wild-type and overexpressed in testicular cancer, we examined abundance
      and localisation of the Chk2 protein during normal development of human testes,
      and at various stages of germ-cell tumour (GCT) pathogenesis. Our results show
      that Chk2 is abundant in foetal germ cells and adult spermatogonia, yet only
      weakly expressed or lacking during the meiotic and later stages of
      spermatogenesis. High levels of Chk2 are detected in the majority of GCTs
      including all pre-invasive carcinoma-in-situ lesions, contrary to variable
      expression and even lack of Chk2 in subsets of invasive GCTs and some teratoma
      structures, respectively. Together with our analyses of cell culture models,
      these results indicate that downmodulation or lack of Chk2 is not simply
      attributable to quiescence or differentiation, they suggest a role for Chk2 in
      mitotic rather than meiotic divisions, support the concept of foetal origin of
      GCTs, and have implications for protein-based screening for tumour-associated
      aberrations of Chk2.

PMID- 11593396
TI  - Identification of a prostate-specific G-protein coupled receptor in prostate
      cancer.
AB  - Membrane receptors coupled to heterotrimeric G-proteins play an essential role in
      the transmission of signals from the extracellular environment to the cytoplasm
      of the cell. A wide variety of external stimuli, including neurotransmitters,
      hormones, phospholipids, photons, odorants, taste ligands, and growth factors,
      can activate specific members of the G-protein coupled receptors (GPCRs). Besides
      essential functions in fully differentiated cells and tissues, GPCRs are also
      involved in embryogenesis, tissue regeneration, cell growth stimulation, and cell
      proliferation. In this study, we identified a novel prostate-specific G-protein
      coupled receptor that interacts with Galpha(12) in our yeast two-hybrid assays.
      The expression of the receptor protein is highly restricted to human prostate
      tissues using multiple-tissue Northern blot analysis, and tissue expression
      array. Furthermore, the expression of prostate-specific receptor is increased
      significantly in prostate tumors in comparison with the matched normal prostate
      tissues using PCR and Southern blot analysis, suggesting a potential role of this
      tissue-specific G-protein coupled receptor in prostate cancer development.

PMID- 11593397
TI  - Suppression of cell spreading by v-Crk requires Ras-MEK-MAP kinase signaling.
AB  - We investigated the attachment and spreading of v-Crk-transformed cells, v
      Crk3Y1, on fibronectin. Transformation by v-Crk virtually suppressed the
      spreading, but not the attachment, of cells on fibronectin. This suppression of
      cell spreading was not correlated with the suppression of integrin alpha5 and
      beta1 expression. However, the spreading of v-Crk3Y1 on fibronectin was
      dramatically restored by either expression of dominant-negative Ras or treatment
      with manumycin A, a Ras farnesyltransferase inhibitor. Moreover, both expression
      of dominant-negative MEK1 and treatment of cells with U0126, a MEK1 inhibitor,
      restored the cell spreading of v-Crk3Y1. In contrast, neither treatment with
      LY294002, a PI3K inhibitor, nor expression of dominant-negative C3G showed no
      effect on cell spreading on fibronectin. Taken together, our results suggest
      that, among multiple signaling pathways activated by v-Crk, the Ras-MEK1-MAP
      kinase cascade plays a pivotal role in the suppression of cell spreading on
      fibronectin, but C3G and the PI3 kinase do not.

PMID- 11593398
TI  - Functional interaction of Yaf2 with the central region of MycN.
AB  - MYCN is often amplified in advanced-stage neuroblastomas with the consequence of
      enhanced MycN protein expression. By employing the yeast two-hybrid system we
      found that Yaf2 binds to the central region of MycN. Binding was also seen in
      vitro and in vivo. Ectopically expressed Yaf2, like MycN, is localized in the
      nuclei of neuroblastoma cells. Endogenous Yaf2 is expressed in all three tested
      neuroblastoma cell lines, all of which also express MycN. Yaf2 was able to
      enhance MycN-mediated transactivation from an E-box promoter, deletion of the
      Yaf2 binding region in MycN abrogates this effect. Thus, the binding of Yaf2 to
      the central region of MycN is functional in mammalian cells.

PMID- 11593399
TI  - Chromosomal localization and promoter analysis of the adenomatous polyposis coli
      binding protein RP1.
AB  - The EB1/RP1 family is a new protein family that is characterized by the ability
      of its members to serve as interacting partners for the adenomatous polyposis
      coli (APC) tumour suppressor protein and tubulin. Data obtained with highly
      conserved yeast homologues suggest that the EB1/RP1 protein family promotes
      cytoplasmic microtubule dynamics and contributes to the sensor mechanism
      controlling the cytokinesis checkpoint during mitosis. However, the precise
      function of this protein family in mammalian cells has not been elucidated so far
      and remains unclear. Here, we report on the genomic localization of the RP1 gene
      and the characterization of the corresponding promoter. The RP1 gene was found to
      be encoded on chromosome 18q21, a locus which is altered or deleted in up to 50%
      of all patients with colorectal cancer. Promoter analysis revealed that the RP1
      gene is under the control of a strong promoter that was 10 times more active in
      mammalian cells when compared to SV40 promoter. Members of the cyclic AMP
      response element binding protein family (CREB1 and CREB2) could be identified as
      transcription factors binding specifically within the RP1 promoter sequence.

PMID- 11593400
TI  - Genomic organization, complex splicing pattern and expression of a human septin
      gene on chromosome 17q25.3.
AB  - The Ov/Br septin gene, which is also a fusion partner of MLL in acute myeloid
      leukaemia, is a member of a family of novel GTP binding proteins that have been
      implicated in cytokinesis and exocytosis. In this study, we describe the genomic
      and transcriptional organization of this gene, detailing seventeen exons
      distributed over 240 kb of sequence. Extensive database analyses identified
      orthologous rodent cDNAs that corresponded to new, unidentified 5' splice
      variants of the Ov/Br septin gene, increasing the total number of such variants
      to six. We report that splicing events, occurring at non-canonical sites within
      the body of the 3' terminal exon, remove either 1801 bp or 1849 bp of non-coding
      sequence and facilitate access to a secondary open reading frame of 44 amino
      acids maintained near the end of the 3' UTR. These events constitute a novel
      coding arrangement and represent the first report of such a design being
      implemented by a eukaryotic gene. The various Ov/Br proteins either differ
      minimally at their amino and carboxy termini or are equivalent to truncated
      versions of larger isoforms. Northern analysis with an Ov/Br septin 3' UTR probe
      reveals three transcripts of 4.4, 4 and 3 kb, the latter being restricted to a
      sub-set of the tissues tested. Investigation of the identified Ov/Br septin
      isoforms by RT-PCR confirms a complex transcriptional pattern, with several
      isoforms showing tissue-specific distribution. To date, none of the other human
      septins have demonstrated such transcriptional complexity.

PMID- 11593401
TI  - The mechanism of cell cycle regulation by v-Src.
AB  - The tyrosine kinase oncoprotein v-Src can overcome the requirements for serum
      growth factors and anchorage which restrain normal cell growth. Here we
      investigated the biochemical mechanisms whereby v-Src induces quiescent cells to
      enter S phase in the absence of serum mitogens. Activating a temperature
      sensitive v-Src in quiescent cells sequentially induced cyclins D1, E and A and
      also down regulated p27. We addressed whether p27 down regulation was required to
      activate cyclin D1/CDK4/6 or cyclin E/CDK2 by engineering cells with inducible
      p27. Both S phase entry and activation of cyclin/CDKs were inhibited by over
      expression of p27. Using cells engineered with inducible p16 we showed that
      Cyclin D/CDK4/6 activity was required for v-Src to increase expression of cyclin
      A but not cyclin E. To determine which downstream kinases mediated these effects
      of v-Src we added pharmacological inhibitors of phosphatidylinositol 3-kinase
      (PI3-K), LY294002 or mitogen activated protein kinase kinase (MEK), U0126. PI3-K
      was required for v-Src to activate MEK and MEK was required for v-Src to increase
      expression of cyclins D1 and E. However, the MEK inhibitor prevented p27 protein
      down regulation whereas the PI3-K inhibitor did not. This was because reduced PI3
      K activity lead to proteolytic degradation of p27.

PMID- 11593402
TI  - Common and reversible regulation of wild-type p53 function and of ribosomal
      biogenesis by protein kinases in human cells.
AB  - Two specific inhibitors of cyclin-dependent kinase 2 (Cdk2), roscovitine and
      olomoucine, have been shown recently to induce nuclear accumulation of wt p53 and
      nucleolar unravelling in interphase human untransformed IMR-90 and breast tumor
      derived MCF-7 cells. Here, we show that the early response of MCF-7 cells to
      roscovitine is fully reversible since a rapid restoration of nucleolar
      organization followed by an induction of p21(WAF1/CIP1), a downregulation of
      nuclear wt p53 and normal cell cycle resumption occurs if the compound is removed
      after 4 h. Interestingly, similar reversible effects are also induced by the
      casein kinase II (CKII) inhibitor, 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole. Upon short-term treatment also, both compounds
      significantly, but reversibly, reduce the level of 45S precursor ribosomal RNA.
      Cells exposed to the two types of protein kinase inhibitors for longer times keep
      exhibiting altered nucleolar and wt p53 features, yet they strikingly
      differentiate in that most roscovitine-treated cells fail to ever accumulate high
      levels of p21(WAF1/CIP1) in contrast with DRB-treated ones. In both cases,
      however, the cells eventually fall into an irreversible state and die. Moreover,
      we found that constitutive overexpression of p21(WAF1/CIP1) alters the nucleolar
      unravelling process in the presence of DRB, but not of roscovitine, suggesting a
      role for this physiological Cdk inhibitor in the regulation of nucleolar
      function. Our data also support the notion that both roscovitine- and DRB
      sensitive protein kinases, probably including Cdk2 and CKII, via their dual
      implication in the p53-Rb pathway and in ribosomal biogenesis, would participate
      in coupling cell growth with cell division.

PMID- 11593403
TI  - Induction of ser15 and lys382 modifications of p53 by blockage of transcription
      elongation.
AB  - Blockage of transcription has been shown to induce the tumor suppressor p53 in
      human cells. We here show that RNA synthesis inhibitors blocking the
      phosphorylation of the carboxyl terminal domain (CTD) of RNA polymerase II, such
      as DRB and H7, induced rapid nuclear accumulation of p53 proteins that were not
      phosphorylated at ser15 or acetylated at lys382. In contrast, agents that inhibit
      the elongation phase of transcription, such as UV light, camptothecin or
      actinomycin D, induced the accumulation of nuclear p53 proteins that were
      modified at both of these sites. Furthermore, using a panel of DNA repair
      deficient cells we show that persistent DNA lesions in the transcribed strand of
      active genes are responsible for the induction of the ser15 and lys382
      modifications following UV-irradiation. We conclude that inhibition of
      transcription is sufficient for the accumulation of p53 in the nucleus regardless
      of whether the ser15 site of p53 is phosphorylated or not. Importantly, blockage
      of the elongation phase of transcription triggers a distinct signaling pathway
      leading to p53 modifications on ser15 and lys382. We propose that the elongating
      RNA polymerase complex may act as a sensor of DNA damage and as an integrator of
      cellular stress signals.

PMID- 11593404
TI  - Early development of polycystic kidney disease in transgenic mice expressing an
      activated mutant of the beta-catenin gene.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is common and is a major
      cause of renal failure. Although the genetics of ADPKD are well known and have
      led to the discovery of polycystins, a new protein family, the pathogenesis of
      the disease remains largely unknown. Recent studies have indicated that the beta
      catenin signaling pathway is one of the targets of the transduction pathway
      controlled by the polycystins. We have generated transgenic mice that overproduce
      an oncogenic form of beta-catenin in the epithelial cells of the kidney. These
      mice developed severe polycystic lesions soon after birth that affected the
      glomeruli, proximal, distal tubules and collecting ducts. The phenotype of these
      mice mimicked the human ADPKD phenotype. Cyst formation was associated with an
      increase in cell proliferation and apoptosis. The cell proliferation and
      apoptotic indexes was increased 4-5-fold and 3-4-fold, respectively, in cystic
      tubules of the transgenic mice compared to that of littermate controls. Our
      findings provide experimental genetic evidence that activation of the Wnt/beta
      catenin signaling pathway causes polycystic kidney disease and support the view
      that dysregulation of the Wnt/beta-catenin signaling is involved in its
      pathogenesis.

PMID- 11593405
TI  - Apoptosis induction in prostate cancer cells by a novel gene product, pHyde,
      involves caspase-3.
AB  - A novel gene, pHyde, was recently cloned from Dunning rat prostate cancer cells.
      A recombinant adenovirus containing pHyde cDNA gene (AdpHyde) was generated to
      investigate the biological function of pHyde protein. AdpHyde inhibited the
      growth of human prostate cancer cells. Apoptosis was induced in AdpHyde
      transduced cells as demonstrated by DAPI (4', 6-diamino-2-phenylindole), TUNEL
      (terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling) staining,
      and flow cytometry assays. Apoptosis was also induced in human xenograft prostate
      cancer tumors growing in nude mice following treatment with AdpHyde. AdpHyde
      transduction resulted in a dose-dependent stimulation of caspase-3 activity in
      DU145 cells which was blocked by DEVD (succinyl-Asp-Glu-Val-Asp-aldehyde) and VAD
      (benzyloxycarbonyl - Val - Ala - Asp -fluoromethylketone), inhibitors
      specifically against caspase-3. Moreover, cancer cells that lacked expression of
      endogenous caspase-3 were not or barely inhibited by pHyde. These results taken
      together suggest that pHyde inhibits cancer growth by inducing apoptosis through
      a caspase-3 dependent pathway.

PMID- 11593406
TI  - Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple
      myeloma.
AB  - Previous studies demonstrate that interleukin-6 (IL-6) mediates growth and
      survival in human multiple myeloma (MM) cells via the MEK/MAPK and JAK/STAT
      signaling pathways, respectively. IL-6 also confers protection against
      Dexamethasone (Dex)-induced apoptosis via activation of protein tyrosine
      phosphatase (SHP2). In the current study, we characterized IL-6 triggered
      phophatidylinositol-3 kinase/Akt kinase (PI3-K/Akt) signaling in MM cells. IL-6
      induces Akt/PKB phosphorylation in a time and dose dependent manner in MM.1S MM
      cells. IL-6 also induced phosphorylation of downstream targets of Akt, including
      Bad, GSK-3beta, and FKHR, confirming Akt activation. Inhibition of Akt activation
      by the PI3-K inhibitor LY294002 partially blocked IL-6 triggered MEK/MAPK
      activation and proliferation in MM.1S cells, suggesting cross-talk between PI3-K
      and MEK signaling. We demonstrate that Dex-induced apoptosis in MM.1S cells is
      mediated by downstream activation of caspase-9, with resultant caspase-3
      cleavage; and conversely, that IL-6 triggers activation of PI3-K and its
      association with SHP2, inactivates caspase-9, and protects against Dex-induced
      apoptosis. LY294002 completely abrogates this signaling cascade, further
      confirming the importance of PI3-K/Akt signaling in conferring the protective
      effect of IL-6 against Dex-induced apoptosis. Finally, we show that IL-6
      triggered PI3-K/Akt signaling in MM.1S cells inactivates forkhead transcriptional
      factor (FKHR), with related G1/S phase transition, whereas LY294002 blocks this
      signaling, resulting in upregulation of p27(KIP1) and G1 growth arrest. Our data
      therefore suggest that PI3-K/Akt signaling mediates growth, survival, and cell
      cycle regulatory effects of IL-6 in MM.

PMID- 11593407
TI  - A "no-hybrids" screen for functional antagonizers of human p53 transactivator
      function: dominant negativity in fission yeast.
AB  - We have developed a functional "no-hybrids" screen in the fission yeast
      Schizosaccharomyces pombe based on the transcription transactivator activity of
      human p53. The screen can be used to identify antagonizers and modulators of p53
      activity. Expression of functional full-length human p53 is conditionally lethal
      to the screen reporter strains. Co-expression of specific inhibitory proteins
      promotes cell survival and growth. We have validated the "no-hybrids" system by
      (a) successful modeling of human wild-type p53 interaction with SV40 large T
      antigen, Mdm2 and a panel of tumor-derived human p53 mutants, (b) demonstrating
      the screening system's efficiency through identification of a dominant negative
      fragment of p53 itself in a library screen context and (c) using Drosophila p53
      to demonstrate that the system can detect evolutionarily distant p53 homologues
      based on their transactivator activity. The "no-hybrids" screen will be of
      utility in searches for p53 function-modulators of both cellular and viral
      origin.

PMID- 11593408
TI  - MMTV promoter hypomethylation is linked to spontaneous and MNU associated c-neu
      expression and mammary carcinogenesis in MMTV c-neu transgenic mice.
AB  - The erbB family of receptor tyrosine kinases is frequently implicated in
      neoplasia. Amplification and overexpression of erbB2/neu has been found in 20 to
      40% of human breast cancers. Previous studies using MMTV/c-neu transgenic mice
      have linked rat neu overexpression to mammary tumor development. In this study,
      we provide evidence that rat neu overexpression in mammary tumors of MMTV/c-neu
      transgenic mice is always associated with demethylation of the MMTV promoter,
      whereas the normal mammary glands of these transgenic mice always contain
      specific methylated regions of the MMTV promoter. In addition, after exposure to
      N-methyl-N-nitrosourea (MNU), the latency of mammary tumor development is
      significantly reduced and again is also associated with MMTV promoter
      demethylation. Thus, the transition from methylation to hypomethylation of the
      MMTV promoter induces high-level expression of c-neu and appears to be a
      prerequisite for transformation from normal to malignant mammary epithelium,
      either spontaneously or after carcinogen exposure. Expression of transgenic c-neu
      from the demethylated MMTV promoter appears to be an early event that allows
      outgrowth of mammary epithelium predisposed to malignant transformation.

PMID- 11593409
TI  - The tyrosine phosphatase SHP-2 is required for mediating phosphatidylinositol 3
      kinase/Akt activation by growth factors.
AB  - SHP-2 is a ubiquitously expressed non-transmembrane tyrosine phosphatase with two
      SH2 domains. Multiple reverse-genetic studies have indicated that SHP-2 is a
      required component for organ and animal development. SHP-2 wild-type and
      homozygous mutant mouse fibroblast cells in which the N-terminal SH2 domain was
      target-deleted were used to examine the function of SHP-2 in regulating
      Phosphatidylinositol 3-Kinase (PI3K) activation by growth factors. In addition,
      SHP-2 and various mutants were introduced into human glioblastoma cells as well
      as SHP-2(-/-) mouse fibroblasts. We found that EGF stimulation and EGFR
      oncoprotein (DeltaEGFR) expression independently induced the co
      immunoprecipitation of the p85 subunit of PI3K with SHP-2. Targeted deletion of
      the N-terminal SH2 domain of SHP-2 severely impaired PDGF- and IGF-induced Akt
      phosphorylation. Ectopic expression of SHP-2 in U87MG gliobastoma cells elevated
      EGF-induced Akt phosphorylation, and the effect was abolished by mutation of its
      N-terminal SH2 domain. Likewise, the reconstitution of SHP-2 expression in the
      SHP-2(-/-) cells enhanced Akt phosphorylation induced by EGF while rescuing that
      induced by PDGF and IGF. Further lipid kinase activity assays confirmed that SHP
      2 modulation of Akt phosphorylation correlated with its regulation of PI3K
      activation. Based on these results, we conclude that SHP-2 is required for
      mediating PI3K/Akt activation, and the N-terminal SH2 domain is critically
      important for a "positive" role of SHP-2 in regulating PI3K pathway activation.

PMID- 11593410
TI  - Ultraviolet light-induced DNA damage triggers apoptosis in nucleotide excision
      repair-deficient cells via Bcl-2 decline and caspase-3/-8 activation.
AB  - Ultraviolet (UV) light is a potent mutagenic and genotoxic agent. Whereas DNA
      damage induced by UV light is known to be responsible for UV-induced
      genotoxicity, its role in triggering apoptosis is still unclear. We addressed
      this issue by comparing nucleotide excision repair (NER) deficient 27-1 and 43-3B
      Chinese hamster (CHO) cells with the corresponding wild-type and ERCC-1
      complemented cells. It is shown that NER deficient cells are dramatically
      hypersensitive to UV-C induced apoptosis, indicating that DNA damage is the major
      stimulus for the apoptotic response. Apoptosis triggered by UV-C induced DNA
      damage is related to caspase- and proteosome-dependent degradation of Bcl-2
      protein. The expression of other members of the Bcl-2 family such as Bax, Bcl
      x(L) and Bak were not affected. Bcl-2 decline is causally involved in UV-C
      induced apoptosis since overexpression of Bcl-2 protected NER deficient cells
      against apoptosis. We also demonstrate that caspase-8, caspase-9 and caspase-3
      are activated and PARP is cleaved in response to unrepaired UV-C induced DNA
      damage. Caspase-8 activation occurred independently of CD95 receptor activation
      since CD95R/FasR and CD95L/FasL were not altered in expression, and transfection
      of transdominant negative FADD failed to block apoptosis. Overall, the data
      demonstrate that UV-C induced non-repaired DNA damage triggers apoptosis in NER
      deficient fibroblasts involving components of the intrinsic mitochondrial damage
      pathway.

PMID- 11593411
TI  - In vivo complex formation of PU.1 with HDAC1 associated with PU.1-mediated
      transcriptional repression.
AB  - We previously reported that overexpression of PU.1, a member of the Ets family of
      transcription factors, induces differentiation inhibition and apoptosis
      associated with c-Myc down-regulation in murine erythroleukemia (MEL) cells. To
      understand the molecular mechanism by which c-Myc is down-regulated due to
      overexpression of PU.1, we performed luciferase reporter assays using the mouse c
      myc promoter. PU.1 repressed the activities of not only the c-myc promoter but
      also several other promoters. Experiments with deletion mutants of PU.1 revealed
      that the C-terminal region spanning amino acids (aa) 123-272 including the PEST
      and ETS domains but not the activation domain was sufficient for this
      transcriptional repression. It was unlikely that the repression was due to
      sequestration of a limited amount of CBP/p300 nor pCAF, because overexpression of
      these co-activators did not relieve PU.1-mediated transcriptional repression.
      Instead, it was found that the C-terminal aa 101-272 of PU.1 formed a complex
      with mSin3A and HDAC1 in vivo, which was speculated to be associated with the
      repression. The C-terminal region of PU.1 also formed a complex with the basic
      transcription factor TBP in vitro and in vivo. Our results suggest that
      overexpression of PU.1 induces transcriptional repression in several gene
      promoters including the c-myc promoter which may be mediated by its complex
      formation with HDACs.

PMID- 11593412
TI  - Increased and correlated nuclear factor-kappa B and Ku autoantigen activities are
      associated with development of multidrug resistance.
AB  - In this study, we investigated possible engagement of NF-kappaB and Ku
      autoantigen (Ku) activation in development of multidrug resistance (MDR) and
      circumvention of MDR by modulation of NF-kappaB and Ku. The NF-kappaB activity
      and NF-kappaB p65 subunit level were constitutively higher in MDR cells than in
      drug-sensitive parental cells. Interestingly, a faster running NF-kappaB DNA
      binding complex was identified as Ku, a DNA damage sensor and a key double strand
      break repair protein, and was positively correlated with the NF-kappaB activity
      in MDR cells and Ku- or both subunits of NF-kappaB-transfected cells. Also both
      NF-kappaB and Ku activities were activated or inhibited by treatment with
      etoposide (VP-16) or MG-132 (a proteasome inhibitor), respectively. Furthermore,
      PKA inhibitor suppressed markedly the constitutive and drug-induced activities of
      NF-kappaB and Ku in MDR cells and subsequently potentiated the cytotoxic activity
      of anticancer drugs. Our results proposed that the NF-kappaB and Ku activation
      could be one of multi-factorial MDR mechanism, and PKA inhibitor, likely via
      inhibition of NF-kappaB and Ku activities, could enhance the effectiveness of
      anticancer drugs against MDR cells with high activities of NF-kappaB and Ku.

PMID- 11593413
TI  - Protein phosphatase 2A interacts with the Src kinase substrate p130(CAS).
AB  - In this study, we report that the Src substrate Cas (p130 Crk-associated
      substrate) associates with protein phosphatase 2A (PP2A), a serine/threonine
      phosphatase. We investigated this interaction in cells expressing a temperature
      sensitive mutant form of v-Src. v-Src activation (by shifting cells from the
      nonpermissive to the permissive temperature) led to an increase in the tyrosine
      phosphorylation of v-Src and Cas, as well as in the association between v-Src and
      Cas. v-Src has previously been shown to bind to PP2A and to phosphorylate the
      catalytic subunit of PP2A, resulting in inhibition of phosphatase activity. We
      found that the association between v-Src and PP2A decreased as cells were shifted
      to the permissive temperature. In contrast, the levels of PP2A that co
      immunoprecipitated with Cas increased when v-Src was activated. We obtained
      similar results in pull-down experiments with immobilized Microcystin, a PP2A
      inhibitor. Serine/threonine phosphorylation of Cas has previously been shown to
      occur in a cell cycle regulated matter. Treatment of NIH3T3 cells with okadaic
      acid, a PP2A inhibitor, augments the serine/threonine phosphorylation of Cas that
      occurs at mitosis. Furthermore, PP2A dephosphorylates serine residues on Cas in
      vitro. Taken together, our results suggest that PP2A may be involved in the cell
      cycle-specific dephosphorylation of Cas.

PMID- 11593414
TI  - Msh2 DNA mismatch repair gene deficiency and the food-borne mutagen 2-amino-1
      methy1-6-phenolimidazo [4,5-b] pyridine (PhIP) synergistically affect mutagenesis
      in mouse colon.
AB  - Msh2 deficiency and food-borne carcinogen PhIP have been implicated as genetic
      and environmental factors, respectively, in human colon carcinogenesis. It is not
      clear whether loss of one or both alleles of Msh2 gene increases the mutational
      sensitivity in colon when exposed to environmental carcinogens. In the current
      study, Msh2(+/-)/lacI and Msh2(-/-)/lacI double transgenic mice were treated with
      PhIP and mutations in the lacI gene were studied in the colon. The spontaneous
      mutation frequency (MF) is approximately eightfold higher in Msh2(-/-) mice than
      in Msh2(+/+) mice, while Msh2(+/-) mice display similar levels of spontaneous
      mutation as the Msh2 wild type mice. PhIP induced a significant increase in MF in
      all genotypes of mice. However, induced MF is much higher in Msh2(-/-) mice
      compared to Msh2(+/+) and Msh2(+/-) mice. Msh2(+/-) mice displayed an increased
      level of G:C>T:A transversions and -1 frameshifts upon PhIP treatment. In
      contrast, loss of both Msh2 alleles mainly results in increased frequency of
      G:C>A:T transitions when exposed to PhIP. These results suggest that a defect in
      mismatch repair may result in an enhanced sensitivity from exposure to a dietary
      carcinogen. It also provides insight into interaction between genetic and
      environmental factors in human carcinogenesis.

PMID- 11593415
TI  - Constitutively active Akt is an important regulator of TRAIL sensitivity in
      prostate cancer.
AB  - TRAIL/Apo-2L is a member of the tumor necrosis factor superfamily and has
      recently been shown to induce apoptosis in cancer cells, but not in normal cells.
      In nude mice injected with human tumors, TRAIL reduces the size of these tumors
      without side effects. Akt promotes cell survival and block apoptosis. Some
      prostate cancer cells express high levels of Akt due to lack of active lipid
      phosphatase PTEN, a negative regulator of PI-3 kinase pathway, which may be
      responsible for drug resistance. The objective of this paper is to investigate
      the intracellular molecules that regulate TRAIL resistance. We have examined
      caspase-8 activity, BID cleavage, Akt activity, mitochondrial membrane potential
      (DeltaPsi(m)) and apoptosis in prostate cancer (LNCap, PC-3, PC-3M and DU145)
      cells treated with or without TRAIL. PC-3, PC-3M and DU145 cells are sensitive to
      TRAIL, whereas LNCap cells are resistant. LNCap cells express the highest level
      of constitutively active Akt, which is directly correlated with TRAIL resistance.
      TRAIL activates caspase-8 in all the cell lines. Downregulation of constitutively
      active Akt by PI-3 kinase inhibitors (wortmannin and LY-294002), dominant
      negative Akt or PTEN, renders LNCap cells sensitive to TRAIL. Inhibition of TRAIL
      sensitivity occurs at the level of BID cleavage. Inhibition of protein synthesis
      by cycloheximide also causes LNCap cells sensitive to TRAIL. Overexpression of
      Bcl-2 or Bcl-X(L) inhibits TRAIL-induced DeltaPsi(m) and apoptosis.
      Overexpression of constitutively active Akt in PC-3M cells (express very low
      levels of constitutively active Akt) restores TRAIL resistance. These data
      suggest that elevated Akt activity protects LNCap cells from TRAIL-induced
      apoptosis, and the PI-3 kinase/Akt pathway may inhibit apoptotic signals by
      inhibiting processing of BID. Thus, constitutively active Akt is an important
      regulator of TRAIL sensitivity in prostate cancer.

PMID- 11593416
TI  - c-myc box II mutations in Burkitt's lymphoma-derived alleles reduce cell
      transformation activity and lower response to broad apoptotic stimuli.
AB  - In addition to c-myc rearrangement, over 50% of Burkitt's lymphoma cases present
      clustered mutations in exon 2, where many of the functional activities of c-Myc
      protein are based. This report describes the functional consequences induced by
      tumour-derived c-myc mutations located in c-myc box II. Two mutated alleles were
      studied, focusing on the P138C mutation, and compared to wild-type c-myc. The c
      Myc transformation, transactivation and apoptosis activities were explored based
      on cells over-expressing c-Myc. While the transcriptional activation activity was
      not affected, our experiments exploring the anchorage-independent growth capacity
      of c-Myc-transfected Rat1a cells showed that c-Myc box II mutants were less
      potent than wild-type c-Myc in promoting cell transformation. Considering the
      possibility that these mutations could be interfering with the ability of c-Myc
      to promote apoptosis, we tested c-Myc-transfected Rat1a fibroblasts under several
      conditions: serum deprivation-, staurosporine- and TNFalpha-induced cell death.
      Interestingly, the mutated alleles were characterized by an overall decrease in
      ability to mediate apoptosis. Our study indicates that point mutations located in
      c-Myc box II can decrease the ability of the protein to promote both
      transformation and apoptosis without modifying its transactivating activity.

PMID- 11593417
TI  - Frequent allelic imbalance at the ATM locus in DNA multiploid colorectal
      carcinomas.
AB  - DNA multiploidy may involve specific DNA ploidy states with respect to genetic
      alterations such as oncogenes, tumor suppressor gene mutation and microsatellite
      instability. To clarify the role of DNA multiploidy in colorectal cancer, we
      analysed allelic imbalance involving the ATM gene, localized to chromosome 11q22
      23 and thought to be involved in genetic stability, in a series of multiploid
      colorectal carcinomas. In addition, p53 gene mutation (exons 5-8) and allelic
      imbalance at 11q24 loci distal to the ATM locus were also examined. The crypt
      isolation technique coupled with DNA cytometric sorting and polymerase chain
      reaction assay using 10 microsatellite markers tightly linked to the ATM gene
      were used to study ATM allelic imbalance in 55 colorectal carcinomas (15 diploid,
      13 aneuploid, 27 multiploid). While allelic imbalance at the ATM locus was rarely
      observed in diploid and aneuploid carcinomas, multiploid carcinomas exhibited a
      high frequency of ATM allelic imbalance. In multiploid carcinoma samples, diploid
      subpopulations showed a smaller range of allelic imbalance at the loci tested
      compared to aneuploid subpopulations that demonstrated allelic imbalance over a
      relatively large region. Also, the frequency of AI at 11q24 showed a similar
      tendency to that at the ATM locus for each DNA ploidy state. An association
      between p53 gene mutation and ATM allelic imbalance in multiploid carcinoma was
      also observed. Our results suggest that ATM allelic imbalance and p53 gene
      mutations occur during the progression from diploid to aneuploid cell populations
      in multiploid colorectal carcinomas.

PMID- 11593418
TI  - G2 phase cell cycle arrest in human skin following UV irradiation.
AB  - The contribution of the short wavelength ultraviolet (UV) component of sunlight
      to the aetiology of skin cancer has been widely acknowledged, although its direct
      contribution to tumour initiation or progression is still poorly understood. The
      loss of normal cell cycle controls, particularly checkpoint controls, are a
      common feature of cancer. UV radiation causes both G1 and G2 phase checkpoint
      arrest in vitro cultured cells. In this study we have investigated the cell cycle
      responses to suberythemal doses of UV on skin. We have utilized short-term whole
      organ skin cultures, and multi parameter immunohistochemical and biochemical
      analysis to demonstrate that basal and suprabasal layer melanocytes and
      keratinocytes undergo a G2 phase cell cycle arrest for up to 48 h following
      irradiation. The arrest is associated with increased p16 expression but no
      apparent p53 involvement. This type of organ culture provides a very useful model
      system, combining the ease of in vitro manipulation with the ability to perform
      detailed molecular analysis in a normal tissue environment.

PMID- 11593419
TI  - Protein phosphatase 1alpha-mediated stimulation of apoptosis is associated with
      dephosphorylation of the retinoblastoma protein.
AB  - Protein phosphatase 1 (PP1) plays important roles in many different aspects of
      cellular activities including cell cycle control. One important function of PP1
      is to activate the retinoblastoma protein pRB. Here we show that pRB is one of
      PP1's downstream targets during apoptosis. When HL-60 cells synchronized at the
      G1/S boundary were treated with pro-apoptotic cytosine arabinoside (araC),
      PP1alpha protein increased twofold and PP1 activity about 30% within 1 h. This
      was followed by pRB dephosphorylation, pRB cleavage by caspases, DNA
      fragmentation, the appearance of cells with <2n DNA content and finally, dying
      and dead cells. In vitro, pRB was protected from caspase-3 digestion by prior Cdk
      mediated phosphorylation, whereas PP1alpha converted phospho-pRB into an
      efficient substrate for caspase-3. Introduction of active PP1alpha into HL-60
      cells by electroporation was sufficient to induce characteristics of apoptosis.
      Similarly, araC-resistant cells, normally unable to die in response to araC,
      initiated apoptosis when electroporated with active PP1alpha. This was also
      accompanied by pRB cleavage. In contrast, introduction of inhibitor-2 delayed the
      onset of araC-induced apoptosis, whereas concomitant introduction of PP1alpha and
      inhibitor-2 completely prevented PP1alpha-induced apoptosis. These results
      suggest that dephosphorylation of key proteins by PP1alpha may be crucial for the
      initiation of apoptosis and further support the concept of PP1 serving as a
      potential target for anti-cancer therapy.

PMID- 11593420
TI  - BRCA1 and GADD45 mediated G2/M cell cycle arrest in response to antimicrotubule
      agents.
AB  - BRCA1 is a tumour suppressor gene implicated in the predisposition to early onset
      breast and ovarian cancer. We have generated cell lines with inducible expression
      of BRCA1 to evaluate its role in mediating the cellular response to various
      chemotherapeutic drugs commonly used in the treatment of breast and ovarian
      cancer. Induction of BRCA1 in the presence of Taxol and Vincristine resulted in a
      dramatic increase in cell death; an effect that was preceded by an acute arrest
      at the G2/M phase of the cell cycle and which correlated with BRCA1 mediated
      induction of GADD45. A proportion of the arrested cells were blocked in mitosis
      suggesting activation of both a G2 and a mitotic spindle checkpoint. In contrast,
      no specific interaction was observed between BRCA1 induction and treatment of
      cells with a range of DNA damaging agents including Cisplatin and Adriamycin.
      Inducible expression of GADD45 in the presence of Taxol induced both G2 and
      mitotic arrest in these cells consistent with a role for GADD45 in contributing
      to these effects. Our results support a role for both BRCA1 and GADD45 in
      selectively regulating a G2/M checkpoint in response to antimicrotubule agents
      and raise the possibility that their expression levels in cells may contribute to
      the toxicity observed with these compounds.

PMID- 11593421
TI  - High mobility group I (Y) proteins bind HIPK2, a serine-threonine kinase protein
      which inhibits cell growth.
AB  - The HMGI proteins (HMGI, HMGY and HMGI-C) have an important role in the chromatin
      organization and interact with different transcriptional factors. The HMGI genes
      are expressed at very low levels in normal adult tissues, whereas they are very
      abundant during embryonic development and in several experimental and human
      tumours. In order to isolate proteins interacting with the HMGI(Y) proteins, a
      yeast two-hybrid screening was performed using the HMGI(Y) protein as bait. This
      analysis led to the isolation of homeodomain-interacting protein kinase-2
      (HIPK2), a serine/threonine nuclear kinase. HIPK2 co-immunoprecipitates with the
      HMGI(Y) protein in 293T cells. The interaction between HIPK2 and HMGI(Y) occurs
      through the PEST domain of HIPK2 and it is direct because in vitro translated
      HIPK2 binds HMGI(Y). We also show that HIPK2 is able to phosphorylate the HMGI(Y)
      protein by an in vitro kinase assay. In order to understand a possible role of
      HIPK2 gene in cell growth we performed a colony assay which showed an impressive
      HIPK2 inhibitory effect on normal thyroid cells. Flow cytometric analysis would
      indicate the block of cell growth at the G2/M phase of the cell cycle. Since
      normal thyroid cells do not express detectable HMGI(Y) protein levels, we assume
      that the HIPK2 inhibitory effect is independent from the interaction with the
      HMGI(Y) protein.

PMID- 11593422
TI  - Point mutations and overexpression of Ron induce transformation, tumor formation,
      and metastasis.
AB  - The receptor tyrosine kinase Ron is a member of the receptor family that includes
      the proto-oncogene Met and the avian oncogene Sea. The interaction of Ron with
      its ligand, known as hepatocyte growth factor-like protein (HGFL) or macrophage
      stimulating protein (MSP), induces crucial cellular responses including invasive
      growth, proliferation, cell scattering, and branching morphogenesis. Based on the
      homology and functional similarities between Met and Ron it was hypothesized that
      Ron may be important in tumor formation and metastasis. To test this hypothesis,
      wild-type mouse Ron and three mutant forms of Ron containing mutations similar to
      those found in the Met gene in human hereditary papillary renal carcinoma (HPRC),
      were expressed in NIH3T3 cells. A transformed phenotype was produced in cell
      lines expressing either wild-type Ron or the mutated Ron proteins. Further, these
      cell lines displayed oncogenic potential by exhibiting increased proliferation
      and constitutive phosphorylation of Ron. These cell lines were also tested for
      the ability to form solid tumors. Cells expressing wild-type Ron and the three
      proteins with single amino acid substitutions were highly tumorigenic in vivo. In
      a model of experimental metastasis, two of the cell lines with altered Ron
      protein formed highly aggressive tumors in the lungs. These results suggest that
      Ron may be an aggressive oncogene when either overexpressed or when activated by
      mutation.

PMID- 11593423
TI  - Role of LXCXE motif-dependent interactions in the activity of the retinoblastoma
      protein.
AB  - Cell cycle control by pRb requires the integrity of the pocket domain, which is a
      region necessary for interactions with a variety of proteins, including E2F and
      LXCXE-motif containing proteins. Through knowledge of the crystal structure of
      pRb we have prepared a panel of pRb mutant derivatives in which a cluster of
      lysine residues that demark the LXCXE peptide binding domain were systematically
      mutated. One of the mutant derivatives, Rb6A, exhibits significantly reduced
      LXCXE-dependent interactions with HPV E7, cyclinD1 and HDAC2, but retained LXCXE
      independent binding to E2F. Consistent with these results, Rb6A could down
      regulate E2F-1-dependent activation of different E2F responsive promoters, but
      was compromised in Rb-dependent repression. Most importantly, Rb6A retained wild
      type growth arrest activity, and colony forming activity similar to wild-type
      pRb. It is compatible with these results that directly targeting HDAC2 to E2F
      responsive promoters as an E2F/HDAC hybrid protein failed to effect cell cycle
      arrest. These results suggest that LXCXE-dependent interactions are not essential
      for pRb to exert growth arrest.

PMID- 11593424
TI  - Protection against chemotherapy-induced cytotoxicity by cyclin-dependent kinase
      inhibitors (CKI) in CKI-responsive cells compared with CKI-unresponsive cells.
AB  - Inactivation of the retinoblastoma (Rb) protein caused by gene mutation,
      association with oncoproteins from small DNA viruses, mutational inactivation of
      p16(Ink4a), or overexpression of cyclin D is a common feature of many human
      cancer cells and is causally associated with the aberrant proliferation control
      of cancer cells; whereas normal cells maintain an integrated cell cycle machinery
      and are subject to cell cycle checkpoint control by cyclin-dependent kinase (CDK)
      inhibitors (CKIs). To determine whether this difference can be translated into a
      therapeutic advantage to protect normal cells from adverse cytotoxicity caused by
      chemotherapy, we established cell model systems for ecdysone-inducible expression
      of p16(Ink4a), p21(Waf1), and p27(Kip1) in one CKI-responsive cell line (A431
      human vulvar epidermoid carcinoma cells with functional Rb) and one CKI
      unresponsive cell line (SiHa human cervical cancer cells with nonfunctional Rb).
      Expression of p16(Ink4a), p21(Waf1), or p27(Kip1) in both SiHa and A431 cells
      strongly inhibited CDK2 activity, indicating functional expression of the CDK
      inhibitors in both cell lines. However, only in A431 cells did expression of
      p16(Ink4a), p21(Waf1), or p27(Kip1) cause Rb dephosphorylation, arrest cell cycle
      traversal, and potently inhibit cell proliferation. Induction of p16(Ink4a),
      p21(Waf1), or p27(Kip1) in SiHa cells failed to cause Rb dephosphorylation or to
      arrest cell cycle traversal, and such induction only minimally inhibited cell
      proliferation. We then compared the chemosensitivity of clones derived from these
      two cell lines when the CKIs were and were not induced. Induction of p16(Ink4a),
      p21(Waf1), or p27(Kip1) conferred strong resistance to paclitaxel- or cisplatin
      mediated cytotoxicity on the CKI-responsive A431 cells but not on the CKI
      unresponsive SiHa cells. Our results support a novel chemotherapy strategy for
      treating patients with Rb pathway-impaired cancers by concurrent administration
      of chemotherapy with CKIs as chemoprotective agents for normal cells.

PMID- 11593425
TI  - Damaged microtubules can inactivate BCL-2 by means of the mTOR kinase.
AB  - Rapamycin, a specific inhibitor of the serine/threonine mTOR kinase, markedly
      inhibited both cell growth and apoptosis in human B-cell lines. Besides arresting
      cells in G(1) by increasing p27(kip1), rapamycin tripled the cellular level of
      the BCL-2 protein. The activity was dose-dependent and specific for the p27(kip1)
      and BCL-2 proteins. Rapamycin did not affect bcl-2 mRNA although it increased
      cellular BCL-2 concentration by inhibiting phosphorylation, a mechanism
      initiating the decay process. To add new insight, we combined rapamycin treatment
      with treatment by taxol, which, by damaging microtubules, can phosphorylate BCL-2
      and activate apoptosis. It was found that the mTOR kinase was activated in cells
      treated with taxol or with nocodazole although it was inhibited in cells pre
      treated with rapamycin. BCL-2 phosphorylation, apoptosis and hyperdiploidy were
      also inhibited by rapamycin. In contrast, taxol-induced microtubule stabilization
      or metaphase synchronization were not inhibited by rapamycin. Taken together,
      these findings indicate that mTOR belongs to the enzymatic cascade that, starting
      from damaged microtubules, phosphorylates BCL-2. By regulating apoptosis, in
      addition to the control of a multitude of growth-related pathways, mTOR plays a
      nodal role in signaling G(1) and G(2)-M events.

PMID- 11593426
TI  - Enhanced expression and activity of DNA polymerase beta in human ovarian tumor
      cells: impact on sensitivity towards antitumor agents.
AB  - DNA polymerase beta, one of the most inaccurate DNA synthesizing enzymes, has
      been shown to confer genetic instability when up-regulated in cells, a situation
      found in several human cancers. Here, we demonstrated that enhanced activity and
      expression of this enzyme occur in the human ovarian tumor 2008/C13*5.25 cells,
      which are resistant to the antitumor agent cisplatin and hypersensitive to 6
      thioguanine. We found that translesion synthesis across platinated DNA crosslinks
      as well as increased incorporation into DNA of 6-thioguanine took place in the
      2008/C13*5.25 cells compared to the parental 2008 cells. Such features being
      molecular signatures of DNA polymerase beta, these findings suggest that
      deregulation of its expression in cancer cells may contribute to the modulation
      of the response to antitumor treatments and therefore to tumor progression.

PMID- 11593427
TI  - Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation.
AB  - We have previously reported that the Jak2 tyrosine kinase but not Jak1 is
      tyrosine phosphorylated in the absence of IL-3 in Bcr-Abl positive M3.16 cells,
      which are rendered IL-3 independent by BCR-ABL gene expression. We have explored
      the involvement of Jak2 tyrosine phosphorylation in Bcr-Abl oncogenic effects.
      Our results indicate that Jak2 became tyrosine-phosphorylated in a number of cell
      lines expressing Bcr-Abl, when maintained in medium lacking IL-3, whereas Bcr-Abl
      negative cells lacked Jak2 tyrosine phosphorylation. Jak2 was poorly tyrosine
      phosphorylated in cells expressing the SH2 deletion mutant of Bcr-Abl compared to
      either wild-type Bcr-Abl or its SH3 deletion mutant. Moreover, tyrosine
      phosphorylation of Jak2 by Bcr-Abl was inhibited by the Abl tyrosine kinase
      inhibitor, STI 571, in a dose-dependent manner. This inhibition of Bcr-Abl kinase
      by the drug did not interfere with the ability of Jak2 and Bcr-Abl to form a
      complex. Studies with deletion mutants of Bcr-Abl indicated that the C-terminal
      domain of Abl within Bcr-Abl was involved in complex formation with Jak2.
      Similarly, GST-Abl pull-down assays confirmed the strong binding to Jak2 by the C
      terminus of Abl. Jak2 peptide substrate studies indicated that the Bcr-Abl and
      Abl tyrosine kinases specifically phosphorylated Y1007 of Jak2 but only poorly
      phosphorylated Y1008. Phosphorylation of Y1007 of Jak2 is known to be critical
      for its tyrosine kinase activation. Tyrosine residue 1007 of Jak2 was
      phosphorylated in 32Dp210 cells as measured by Western blotting with a
      phosphotyrosine 1007 sequence-specific antibody. A kinase-inactive Jak2 mutant
      blocked the colony forming ability of K562 cells. Tumor formation of K562 cells
      in nude mice was similarly inhibited by this kinase-inactive Jak2 mutant. This
      inhibition was independent of Stat5 tyrosine phosphorylation. Furthermore,
      tyrosine-phosphorylated Jak2 was detected in blood cells from CML patients in
      blast crisis but not in a normal marrow sample. In summary, these findings
      provide strong evidence that the Jak2 tyrosine kinase is a critical factor in Bcr
      Abl malignant transformation.

PMID- 11593428
TI  - Oral cancer in vivo gene expression profiling assisted by laser capture
      microdissection and microarray analysis.
AB  - Large scale gene expression profiling was carried out on laser capture
      microdissected (LCM) tumor and normal oral epithelial cells and analysed on high
      density oligonucleotide microarrays. About 600 genes were found to be oral cancer
      associated. These oral cancer associated genes include oncogenes, tumor
      suppressors, transcription factors, xenobiotic enzymes, metastatic proteins,
      differentiation markers, and genes that have not been implicated in oral cancer.
      The database created provides a verifiable global profile of gene expression
      during oral carcinogenesis, revealing the potential role of known genes as well
      as genes that have not been previously implicated in oral cancer.

PMID- 11593429
TI  - Deregulated c-Myb expression in murine myeloid leukemias prevents the up
      regulation of p15(INK4b) normally associated with differentiation.
AB  - Deregulated expression of the proto-oncogene c-myb, which results from provirus
      integration, is thought to be responsible for transformation in a set of murine
      leukemia virus (MuLV)-induced myeloid leukemias (MML). We reported recently that
      this transcription factor promotes proliferation by directly transactivating c
      myc and inhibits cell death through its up-regulation of Bcl-2 (Schmidt et al.,
      2000). To understand more about how these cells become transformed we looked at
      how they deal with cellular pathways inducing growth arrest. Specifically, we
      were interested in the expression of the tumor suppressor gene Cdkn2b
      (p15(INK4b)) in MML because this gene is expressed during myeloid differentiation
      and its inactivation by methylation has been shown to be important for the
      development of human acute myeloid leukemia. mRNA levels for p15(INK4b) and
      another INK4 gene p16(INK4a) were examined in monocytic Myb tumors and were
      compared with expression of the same genes in c-myc transformed monocytic tumors
      that do not express c-Myb. The Cdkn2a (p16(INK4a)) gene was generally not
      expressed in either tumor type, an observation explained by methylation or
      deletion in the promoter region. Although Cdkn2b (p15(INK4b)) mRNA was expressed
      in the Myc tumors, many transcripts were aberrant in size and contained only exon
      1. Surprisingly, in the majority of the Myb tumors there was no p15(INK4b)
      transcription and neither deletion nor methylation could explain this result.
      Additional experiments demonstrated that, in the presence of constitutive c-Myb
      expression, the induction of p15(INK4b) mRNA that accompanies differentiation of
      M1 cells to monocytes does not occur. Therefore, the transcriptional regulator c
      Myb appears to prevent activation of a growth arrest pathway that normally
      accompanies monocyte maturation.

PMID- 11593430
TI  - HER2/Neu-mediated activation of the ETS transcription factor ER81 and its target
      gene MMP-1.
AB  - In this study, we show that the ETS transcription factor ER81 directly binds to
      and activates the promoter of the matrix metalloproteinase gene, MMP-1. Further,
      the oncoprotein HER2/Neu synergizes with ER81 to stimulate MMP-1 transcription.
      The activation of ER81 by HER2/Neu is mediated by MAP kinases, which
      phosphorylate ER81 in its N-terminal activation domain. Four respective
      phosphorylation sites have been identified. Blocking phosphorylation at these
      sites decreases ER81 transcriptional activity, which can be further diminished by
      abolishment of phosphorylation at two non-MAP kinase sites. Altogether, our
      results reveal mechanisms of how phosphorylation of ER81 regulates the expression
      of target genes such as MMP-1, which may be important for many physiological
      processes from embryogenesis to adulthood as well as for tumor metastasis.

PMID- 11593431
TI  - MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic
      AMP-dependent protein kinase in lymphocytes.
AB  - AML1-MTG8 chimeric oncogene is generated in acute myelogenous leukemia with
      t(8;21), and seems to be responsible for the pathogenesis of the disease.
      However, the role of MTG8 is ambiguous. Here we found that MTG8 interacted with
      the regulatory subunit of type II cyclic AMP-dependent protein kinase (PKA
      RIIalpha). The binding site of MTG8 was NHR3 domain, and that of RIIalpha was the
      N-terminus for interacting with PKA anchoring proteins (AKAPs). NHR3 contains a
      putative alpha-amphipathic helix which is characteristic in binding of AKAPs with
      RII. Indirect immunofluorescence microscopy showed that MTG8 and RIIalpha were
      overlapped at the centrosome-Golgi area in lymphocytes. These findings suggest
      that MTG8 may function as an AKAP at the centrosome-Golgi area in lymphocytes.

PMID- 11593432
TI  - Identification of human cancer-related genes by naturally occurring Hepatitis B
      Virus DNA tagging.
AB  - Proviral tagging has been used in animals as a powerful tool for cancer genetics.
      We show that a similar approach is possible in patients with hepatocellular
      carcinoma (HCC) infected by Hepatitis B Virus (HBV), a human pararetrovirus which
      may act by insertional mutagenesis. In this work, the HBV genome is used as a
      probe to identify cancer-related genes. By using HBV-Alu-PCR, we obtained 21
      HBV/cellular DNA junctions from 18 different patients. In six of 21, we found the
      HBV DNA integrated into a cellular gene: (1) Sarco/Endoplasmic Reticulum Calcium
      ATPase1 Gene; (2) Thyroid Hormone Receptor Associated Protein 150 alpha Gene; (3)
      Human Telomerase Reverse Transcriptase Gene; (4) Minichromosome Maintenance
      Protein (MCM)-Related Gene; (5) FR7, a new gene expressed in human liver and
      cancer tissues; and (6) Nuclear Matrix Protein p84 Gene. Seven junctions
      contained unique cellular sequences. In the remaining eight, the HBV DNA was next
      to repetitive sequences, five of them of LINE1 type. The cellular genes targeted
      by HBV are key regulators of cell proliferation and viability. Our results show
      that studies on HBV-related HCCs allow to identify cellular genes involved in
      cancer. We therefore propose this approach as a valuable tool for functional
      cancer genomic studies in humans.

PMID- 11593433
TI  - Bias in detection of instability of the (C)8 mononucleotide repeat of MSH6 in
      tumours from HNPCC patients.
AB  - Recently, we and others reported instability in the (C)8 repeat in exon 5 of MSH6
      as a preferential target for somatic mutations in tumours from MSH6 germline
      mutation carriers. Here, we report that in 45% of tumours from MLH1, MSH2 and
      MSH6 germline mutation carriers no sequence change in the (C)8 repeat of MSH6 was
      found upon DNA sequencing analysis of PCR products with a shift in
      electrophoresis mobility. Using "standard" PCR primers a high frequency of
      instability (50-86%) of the (C)8 repeat was found, but using a modified PCR
      reverse primer, accomplishing modulation of non-templated addition of adenine
      during in vitro PCR amplification by the Taq polymerase, a markedly lower
      frequency of instability was found in tumours from MLH1, MSH2 and MSH6 mutation
      carriers (6, 13 and 40%, respectively). Furthermore, a significant difference of
      the frequency of instability of the (C)8 repeat in tumours from MSH6 mutation
      carriers was found compared to MLH1, MSH2 mutation carriers. These results might
      have important implications for the detection of instability of other short
      mononucleotide repeats, e.g. TGFbetaRII, BAX, IGFRII, PTEN, BRCA2.

PMID- 11593434
TI  - Loss of heterozygosity analysis defines a 3-cM region of 15q commonly deleted in
      human malignant mesothelioma.
AB  - Previous comparative genomic hybridization and allelic loss analyses demonstrated
      frequent deletions from 15q11.1-15 in malignant mesothelioma. Recurrent losses of
      15q11-22 have also been reported in several other tumor types such as breast and
      colorectal cancers. To more precisely map the commonly deleted region, we have
      performed a high density loss of heterozygosity analysis of 46 malignant
      mesotheliomas, using 26 polymorphic microsatellite markers spanning the entire
      long arm of chromosome 15. Allelic loss from 15q was observed in 22 of 46 (48%)
      cases. These analyses have defined a minimally deleted region of approximately 3
      cM, which was confirmed to reside at 15q15 by fluorescence in situ hybridization
      analysis with yeast artificial chromosome probes. No tumor suppressor genes have
      been reported to map to this site. The minimally deleted region identified in
      this investigation overlaps those observed in other kinds of cancer, and is the
      smallest site of recurrent 15q loss identified to date in human tumors. The
      identification of this commonly deleted site implicates a putative tumor
      suppressor gene(s) at 15q15 involved in diverse forms of human neoplasia.

PMID- 11593435
TI  - Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis.
AB  - Mutation of the adenomatous polyposis coli (APC) gene and the subsequent
      dysregulation of beta-catenin are well-documented abnormalities in familial
      adenomatous polyposis (FAP), as well as sporadic polyposis. Intriguingly,
      overexpression of the integrin-linked kinase (ILK) has been shown to modulate
      beta-catenin subcellular localization and function. However, the significance of
      this finding for human carcinogenesis remains unclear. Here, we report the
      increased biochemical activity and expression of ILK protein in polyps from FAP
      patients. Furthermore, dramatic increases in ILK immunoreactivity were observed
      in all abnormal crypts from sporadic polyps, when compared with the normal
      appearing crypts within the same resected specimens. As sulindac and aspirin are
      the two most important therapeutic/chemopreventative agents demonstrated in
      colorectal carcinogenesis, in both humans and animals, further investigation
      revealed that these non-steroidal anti-inflammatory drugs (NSAIDs) target ILK and
      ILK-mediated events in vivo. These include inhibition of, both the biochemical
      activation of ILK, inhibition of serine 9 GSK3beta phosphorylation and the
      enhancement of TCF-4 transcriptional activity. In conclusion, ILK protein
      hyperexpression appears to be an early event in colonic polyposis. Additionally,
      ILK signaling is shown to undergo modulation by sulindac (and aspirin) for the
      first time, indicating that it is likely to be one of the targets affected by
      these agents in vivo.

PMID- 11593436
TI  - Overexpression of candidate tumor suppressor gene FUS1 isolated from the 3p21.3
      homozygous deletion region leads to G1 arrest and growth inhibition of lung
      cancer cells.
AB  - Recently we identified FUS1 as a candidate tumor suppressor gene (TSG) in the 120
      kb 3p21.3 critical region contained in nested lung and breast cancer homozygous
      deletions. Mutation of FUS1 is infrequent in lung cancers which we have confirmed
      in 40 other primary lung cancers. In addition, we found no evidence for FUS1
      promoter region methylation. Because haploinsufficiency or low expression of Fus1
      may play a role in lung tumorigenesis, we tested the effect of exogenously
      induced overexpression of Fus1 protein and found 60-80% inhibition of colony
      formation for non-small cell lung cancer lines NCI-H1299 (showing allele loss for
      FUS1) and NCI-H322 (containing only a mutated FUS1 allele) in vitro. By contrast,
      a similar level of expression of a tumor-acquired mutant form of FUS1 protein did
      not significantly suppress colony formation. Also, induced expression of Fus1
      under the control of an Ecdysone regulated promoter decreased colony formation
      75%, increased the doubling time twofold, and arrested H1299 cells in G1. In
      conclusion, our data are consistent with the hypothesis that FUS1 may function as
      a 3p21.3 TSG, warranting further studies of its function in the pathogenesis of
      human cancers.

PMID- 11593437
TI  - Activation of the RacGTPase inhibits apoptosis in human tumor cells.
AB  - The small GTP-binding protein Rac is a downstream effector of the oncogene
      product p21-ras. Rac is involved in actin polymerization, Jun kinase activation,
      and intracellular superoxide anion production, through distinct pathways in tumor
      cells. Here we investigated the role of activated Rac in the response of tumor
      cells to apoptosis triggered by anti-cancer drugs or the cell surface death
      receptor CD95. Using M14 melanoma cells stably transfected with a constitutively
      active form of Rac1, we show that activated Rac inhibits tumor cell response to
      apoptosis. The inhibitory effect of activated Rac on apoptotic signaling is
      mediated by the interaction of Rac with intracellular oxidase and the subsequent
      production of superoxide, which is supported by experiments performed with M14
      and NIH3T3 cells transiently transfected with the loss-of-function mutants of Rac
      in an activated RacV12 background. Consistent with these findings, we also
      demonstrate that inhibition of the Rac pathway in the HaRas-expressing T24
      bladder carcinoma cell line induces a decrease in superoxide anion concentration,
      and results in a significant increase in tumor cell sensitivity to apoptosis.
      These findings demonstrate the existence of a novel Rac-dependent survival
      pathway mediated by intracellular superoxide in tumor cells.

PMID- 11593438
TI  - Evaluate! Evaluate!

PMID- 11593439
TI  - Evaluation of an inter-organizational prevention program against injuries among
      the elderly in a WHO Safe Community.
AB  - The aim of the study was to evaluate the outcome of a participatory community
      based prevention program against injuries among the elderly. A population-based
      quasi-experimental design was used with pre- and post-implementation measurements
      in an intervention and a control area. The program was based on cross-sectoral
      participation in detecting and taking action against injuries among the elderly.
      Change in the relative risk of injury was estimated by the odds ratio. Morbidity
      in moderately (AIS 2) severe injury in the study area was reduced from 46 per
      1000 population years to 25 per 1000 population years (odds ratio 0.55; 95%
      confidence interval 0.46-0.65), while the minor (AIS 1) injuries increased (odds
      ratio 1.55; 95% confidence interval 1.21-1.91). The risk of severe or fatal (AIS
      3-6) injuries remained constant. In the study area, only a slight decrease in the
      total morbidity rate was observed (odds ratio 0.87; 95% confidence interval 0.77
      0.99). In the control area, there was no evident change in the total morbidity
      rates. Falls decreased or showed a tendency to decrease in the age groups 65 to
      79-y-old in the study area, while they increased in the older age group. The
      results indicate that no sharp boundaries should be drawn between safety
      education, physical conditioning, environmental adjustments and secondary
      prevention measures when planning safety promotion among the elderly. Future
      studies should address these issues along with the methodological complexity
      associated with assessment of participatory community-based safety promotion
      programs.

PMID- 11593440
TI  - A cost-benefit analysis of the community-based injury prevention programme in
      Motala, Sweden--a WHO Safe Community.
AB  - The objective in this study was to calculate costs and benefits caused by a safe
      community injury prevention programme in Motala, Sweden. The study design was a
      quasi-experimental evaluation involving an intervention population and a non
      random control population. All injuries were recorded before and after an
      intervention programme. The presented calculations show that costs of injuries in
      a societal perspective decreased from 116 million Swedish Crowns (SEK) to 96
      million SEK, while the cost for the intervention was estimated at approximately
      10 million SEK. Thus, the safe community injury prevention programme in Motala
      should be judged as cost-effective.

PMID- 11593441
TI  - Mortality and quality of life after trochanteric hip fracture.
AB  - The objective was to evaluate the survival and some aspects of the quality of
      life of patients with trochanteric hip fracture after long-term follow-up in
      comparison with the age- and sex-matched controls without fracture. Two hundred
      consecutive patients (mean age at fracture 77 y) with trochanteric hip fractures
      were compared with the age- and sex-matched controls representing an average
      population from the same area. After a mean 7 y follow-up period a questionnaire
      concerning their place of residence, ambulation, causes leading to impairment,
      need for locomotor aids and management of activities in daily living (ADL)
      functions was sent to the surviving patients and controls. Mortality increased
      gradually being 4.5 percent above the control level one month after the fracture,
      6.0 percent above at three months, 3.5 percent above at one year, 4.5 percent
      above at two years, 6.5 percent above at five years and 9.0 percent above at six
      years. Thirty (48%) of the surviving 62 patients and 83 (90%) of the 92 surviving
      controls were living in their own homes and 2 (3%) and 4 (4%) in service
      apartments respectively. Seventeen (27%) of patients alive were institutionalized
      in a chronic care hospital unit and 13 (21%) in an old people's home as compared
      with 2 (2%) and 3 (3%) of the controls respectively. Twenty-two (35%) of the
      patients and 73 (79%) of the controls were able to move about independently. The
      patients were significantly worse at ADL-management, required more home help and
      had fewer social contacts and outdoor hobbies than the controls. In conclusion
      surgically-treated trochanteric hip fractures markedly increase mortality rate,
      reduce independence and impair walking ability and ADL-functions, and thus
      seriously affect the health-related quality of life of the patients. This fact
      should be considered in the planning of the healthcare of elderly people.

PMID- 11593442
TI  - Life expectancies for individuals with psychiatric diagnoses.
AB  - The aim of the study was to estimate life expectancies in different diagnostic
      groups for individuals treated as inpatients at Swedish psychiatric clinics. All
      individuals, older than 18 y and alive on the first of January 1983, who had been
      registered in the National Hospital Discharge Registry by a psychiatric clinic in
      1978-82, were monitored for mortality during 1983 by using the National Cause of
      Death Registry. The study group consisted of 91 385 men and 77 217 women. The
      patients were divided into nine diagnostic groups according to the principal
      diagnosis registered at the latest discharge. Actuarial mathematics was used to
      construct life expectancy tables, which present the number of years expected to
      live, by gender and diagnostic group. Expectancies of life were significantly
      shortened for both genders and in all nine diagnostic groups (with one
      exception). Mental disorders in general are life shortening. This fact should be
      recognised in community health when setting health priorities. It should also be
      addressed in curricula as well as in treatment and preventive programmes.

PMID- 11593443
TI  - Mortality trends from oral cancer in Andalusia, Spain, 1975-1998.
AB  - Morbidity and mortality rates from oral cancer appear to be on the rise among
      developed countries throughout the world during the last decades. The object of
      the present study was to investigate the recent changes in the mortality from
      oral cancer in the more than seven million inhabitants of Andalusia, Spain. Data
      on the number of deaths by oral cancer from 1975 to 1998 were obtained from
      annual publications by the Statistics Institute. Crude, age-standardized,
      truncated, cumulative and age-specific rates of mortality were calculated by
      gender as well as potential years of life lost rates. Poisson regression models
      were fitted in order to quantify the influence of age and year of death on the
      mortality rates by gender.Age-adjusted mortality rates increased from 2.79 in
      1975-79 to 3.41 in 1995-98 in males and from 0.39 to 0.45 in females during the
      same period. Increases were more marked when comparing the truncated age-adjusted
      rates. Relative risks increased with age from 2.35 to 23.12 in 55 to 64-y-old and
      85-y-old males respectively, and from 2.91 to 21.50 in 55 to 64-y-old and 85-y
      old females respectively, when comparing with the 35-54-y-old age group. There
      was an interaction between age at death and year of death in males but not in
      females. Mortality from oral cancer increased in males in Andalusia over the
      study period, simultaneous to an important change in the pattern of occurrence by
      age. There was a cohort effect in males and females across the studied time
      interval.

PMID- 11593444
TI  - Workplace conditions predict the risk of premature death and functional
      dependence after retirement--results of a gerontological follow-up study in
      Germany.
AB  - Between 1983 and 1985, 595 employees who were entering retirement in East Germany
      were given a medical examination and asked to assess their workplace conditions.
      Ten years later, we examined whether occupational predictors were associated with
      death and functional dependence among the study participants and assessed how the
      surviving pensioners coped with activities and instrumental activities of daily
      living. We assigned the occupational factors reported between 1983 and 1985 to
      two scales: demands and resources. Multiple logistic regression analyses were
      carried out to examine the association of occupational and medical predictors
      with the outcome variables death and functional dependence. Workplace resources
      but not demands were significantly associated with a reduced chance of death in
      women, independent of medical diagnoses. For men neither of these associations
      were verified. Concerning functional dependence individual items such as 'control
      over work content' (for both sexes) significantly reduced the risk of developing
      ADL-dependence. The associations remained stable after medical diagnoses were
      additionally taken into consideration. The results of our study highlight the
      influence of occupational factors beyond working life and support the importance
      of starting geriatric health promotion before retirement age.

PMID- 11593445
TI  - Factors associated with the condoning of female genital mutilation among
      university students.
AB  - Female genital mutilation (FGM) is practiced in Egypt, despite its recent ban,
      generally in rural and uneducated communities, under unsanitary conditions and by
      non-medical personnel. Immediate and long-term complications are frequent. The
      aim of this study was to gain insight into what beliefs or knowledge are
      conducive to supporting FGM. One thousand and seventy university students in
      Cairo, Egypt were randomly selected. A 32-item questionnaire was used to
      interview students regarding their knowledge and attitudes toward FGM.
      Multivariable analyses were performed to find factors associated with being
      against the abolishment of FGM.The response rate was 95% (n=1020). Twenty-eight
      percent of the students support FGM. The most significant factors associated with
      the condoning of FGM were believing FGM has a religious basis (OR=2.53),
      disagreeing that FGM is a custom with no other basis (OR=2.59), not believing it
      is harmful (OR=4.11), and ignoring that it is usually followed by complications
      (OR=5.14). Even in an educated population, a considerable amount of ignorance
      concerning FGM exists. Widespread education about FGM is important to dispel the
      myths that surround its practice and to bring the practice to an end.

PMID- 11593446
TI  - Prenatal screening for Down's syndrome: some psychosocial implications of a
      'screening for all' policy.
AB  - The National Screening Committee of the Department of Health has made
      recommendations to the Government advising that prenatal screening for Down's
      syndrome should be offered to all pregnant women regardless of their age. As most
      women over 35 are already offered some form of testing, affected pregnancies in
      younger women will account for the majority of any increased overall detection
      rate. Therefore, while a 'screening for all' policy will offer wider reproductive
      choices to more women, it is likely to specifically increase the number of young
      women experiencing termination of pregnancy for abnormality. A number of inter
      dependent factors predispose some women to high levels of psychological distress
      following termination, and a combination of these factors is most likely to be
      found in the very young. In addition, very young women often have little
      knowledge of prenatal testing and may be more likely to accept screening
      presented as 'routine' without considering the consequences. At the point where
      decisions about diagnostic testing or termination are made, more specialised
      support may be indicated for some very young women. If the UK National Screening
      Committee's recommendations are taken forward therefore, service providers should
      ensure suitable support is available for some of their more vulnerable clients.

PMID- 11593447
TI  - Tetanus immunization in pregnant women: evaluation of maternal tetanus
      vaccination status and factors affecting rate of vaccination coverage.
AB  - The objectives of this study were to determine the tetanus vaccination status for
      pregnant women, and to examine the effects of various factors on tetanus toxoid
      (TT) vaccination coverage during pregnancy in reproductive-age women. Four
      hundred and ninety-three postpartum women who had live births at a hospital in
      Ankara were interviewed and information was collected on the mothers'
      sociodemographic characteristics, TT vaccination history, and prenatal care
      during the pregnancy studied. The rates for no vaccination, one-dose vaccination,
      and two-dose vaccination were 53.3%, 18.9%, and 27.8%, respectively. The
      vaccinated women (with at least one dose) were significantly younger, of lower
      parity, and had attended more prenatal care visits than the unvaccinated women.
      Of the women who attended at least one prenatal care check-up, only about half
      were vaccinated. Significantly more rural women were vaccinated against tetanus
      than urban women. Current vaccination rates with TT during pregnancy were found
      to be well below universal levels. Turkey needs to launch effective mass media
      campaigns that target urban and suburban populations, and inform and motivate
      women to request vaccination against tetanus.

PMID- 11593450
TI  - Huntington disease phenocopy is a familial prion disease.
AB  - Huntington disease (HD) is a common autosomal dominant neurodegenerative disease
      with early adult-onset motor abnormalities and dementia. Many studies of HD show
      that huntingtin (CAG)n repeat-expansion length is a sensitive and specific marker
      for HD. However, there are a significant number of examples of HD in the absence
      of a huntingtin (CAG)n expansion, suggesting that mutations in other genes can
      provoke HD-like disorders. The identification of genes responsible for these
      "phenocopies" may greatly improve the reliability of genetic screens for HD and
      may provide further insight into neurodegenerative disease. We have examined an
      HD phenocopy pedigree with linkage to chromosome 20p12 for mutations in the prion
      protein (PrP) gene (PRNP). This reveals that affected individuals are
      heterozygous for a 192-nucleotide (nt) insertion within the PrP coding region,
      which encodes an expanded PrP with eight extra octapeptide repeats. This reveals
      that this HD phenocopy is, in fact, a familial prion disease and that PrP repeat
      expansion mutations can provoke an HD "genocopy." PrP repeat expansions are well
      characterized and provoke early-onset, slowly progressive atypical prion diseases
      with an autosomal dominant pattern of inheritance and a remarkable range of
      clinical features, many of which overlap with those of HD. This observation
      raises the possibility that an unknown number of HD phenocopies are, in fact,
      familial prion diseases and argues that clinicians should consider screening for
      PrP mutations in individuals with HD-like diseases in which the characteristic HD
      (CAG)n repeat expansions are absent.

PMID- 11593452
TI  - [The influence of psychosocial factors on the immune system
      (psychoneuroimmunology) and their role for the incidence and progression of
      cancer].
AB  - Psychoneuroimmunological research investigates the influence of psychosocial
      factors on the immune systems. We reviewed clinical studies dealing with the
      following three topics: life events, psychological/psychopathological factors and
      social support, and their influence on cellular and humoral immune activity.
      There is strong evidence that stressful life events (especially losses) have a
      decreasing effect on immunity. Depression has a similar effect and may be the
      mediator between life events and the immune systems. Results dealing with the
      influence of social support on immune functions are still inconclusive. In the
      second part, we reviewed prospective studies concerning the role of psychosocial
      factors on cancer incidence and progression. Most of the life event studies
      reviewed have methodological problems, thus the results are heterogenous. There
      is some evidence that psychological/psychopathological factors can promote cancer
      progression. This is even more obvious in case of insufficient social support.

PMID- 11593451
TI  - Large upward bias in estimation of locus-specific effects from genomewide scans.
AB  - The primary goal of a genomewide scan is to estimate the genomic locations of
      genes influencing a trait of interest. It is sometimes said that a secondary goal
      is to estimate the phenotypic effects of each identified locus. Here, it is shown
      that these two objectives cannot be met reliably by use of a single data set of a
      currently realistic size. Simulation and analytical results, based on variance
      components linkage analysis as an example, demonstrate that estimates of locus
      specific effect size at genomewide LOD score peaks tend to be grossly inflated
      and can even be virtually independent of the true effect size, even for studies
      on large samples when the true effect size is small. However, the bias diminishes
      asymptotically. The explanation for the bias is that the LOD score is a function
      of the locus-specific effect-size estimate, such that there is a high correlation
      between the observed statistical significance and the effect-size estimate. When
      the LOD score is maximized over the many pointwise tests being conducted
      throughout the genome, the locus-specific effect-size estimate is therefore
      effectively maximized as well. We argue that attempts at bias correction give
      unsatisfactory results, and that pointwise estimation in an independent data set
      may be the only way of obtaining reliable estimates of locus-specific effect-and
      then only if one does not condition on statistical significance being obtained.
      We further show that the same factors causing this bias are responsible for
      frequent failures to replicate initial claims of linkage or association for
      complex traits, even when the initial localization is, in fact, correct. The
      findings of this study have wide-ranging implications, as they apply to all
      statistical methods of gene localization. It is hoped that, by keeping this bias
      in mind, we will more realistically interpret and extrapolate from the results of
      genomewide scans.

PMID- 11593453
TI  - [Cortisol in night-urine: Introduction of a research method in
      psychoneuroendocrinology].
AB  - Cortisol is one of the major parameters investigated in
      psychoneuroendocrinological research, but the methods employed for sample
      collecting are often unsatisfactory. A suitable method of sample collection
      should allow for the integrative assessment of long-term changes of the HPA
      system, should be non-invasive, and should not exceed the subject's compliance.
      The assessment of cortisol in night-urine fulfils these demands; although this
      method has been occasionally employed, it has not yet been described
      systematically. For the first time a detailed description is given here that
      allows for a standardized replication. In ten previous studies and three
      investigations of our own this method has been successfully applied to detect
      changes in the cortisol excretion of patients with endocrinological and
      psychiatric disorders as well as in subjects under conditions of psychosocial
      stress. The determination of cortisol in night-urine represents an ideal method
      for the assessment of changes in the basal HPA-activity in numerous areas of
      psychoneuroendocrinological research, e.g. field and screening studies in natural
      environment, clinical studies in psychiatry and especially follow-up studies in
      psychotherapy research.

PMID- 11593455
TI  - [Psychosocial stress induces molecular and structural alterations in the brain -
      How animal experiments help to understand pathomechanisms of depressive
      illnesses].
AB  - Affective disorders are accompanied by central nervous changes that may lead to
      diseases of brain and peripheral organs. To gain an insight into neurobiological
      mechanisms that underlie such diseases we are studying tree shrews (Tupaia
      belangeri). This animal model is based on the fact that male tree shrews are very
      territorial and that under laboratory conditions, two males establish a clear
      social rank order with a dominant and a subordinate animal. In the visual
      presence of the dominant, the subordinate shows all typical signs of stress with
      pronounced activation of the hypothalamic-pituitary-adrenal axis and of the
      sympathetic nervous system. If there are daily confrontations with the dominant
      during a time period of several weeks, the subordinate experiences chronic
      psychosocial stress. Tree shrews can be regarded as a suitable animal model to
      investigate the neurobiological basis of affective disorders since (1) behavioral
      and endocrine symptoms of subordinates resemble those of depressive patients, (2)
      antidepressant treatments lead to an improvement of symptoms, and (3) also in
      humans chronic stress can lead to depression. Using this model we showed that
      chronic stress induces changes in the morphology of hippocampal pyramidal
      neurons, affects neurogenesis in the hippocampal formation, and changes the
      expression of glucocorticoid, serotonergic and noradrenergic receptors in the
      brain. These changes depend on the duration of the stress period with some of the
      alterations being reversible whereas others persist during a longer time period.
      Since the above receptors modulate neuronal activity, the stress induced
      alterations lead to an impairment of neuronal activity in distinct brain regions.

PMID- 11593454
TI  - [The influence of daily psychosocial stressors and associated emotions on the
      dynamic course of urine cortisol and urine neopterin in systemic lupus
      erythematosus: Experience taken from two "integrative single-case studies"].
AB  - Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized
      by flare-ups, the cause of which is unknown. According to new stress concepts,
      two "integrative single-case studies" have been conducted in order to gather
      evidence about whether daily stressful incidents and associated emotions
      interfere with the dynamics of urine cortisol and urine neopterin in SLE.
      Patients under study collected their urine at home, for a period of at least 50
      days, on a daily basis, divided into day and night urine. Additionally, patients
      filled out questionnaires twice a day to determine their emotional state, life
      style and disease activity. Each week, patients were examined clinically and
      interviewed to identify the past week's stressors using the Incidents and Hassles
      Inventory (IHI, Brown and Harris). Statistical analysis of the serial data was
      performed using time-series analysis according to Box and Jenkins. In both
      "integrative single-case studies" we were able to demonstrate that stressful
      incidents predicted an increase in urine neopterin 36 hours (Case 1) to 60 hours
      (Case 2) later (p < 0.05). Additionally, in Case 1 the neopterin levels were
      highly associated with stress resulting from the weekly examinations and
      interviews. Furthermore, in Case 2 it turned out that depending on their
      predictability stressful incidents were preceded by a decrease in urine cortisol
      12 hours earlier or were followed by a decrease in urine cortisol 36 hours later.
      And finally, emotional irritation was highly correlated with the course of urine
      neopterin. In Case 2 irritation led to an increase in urine neopterin 84 hours
      later. There were no clinical signs of SLE during both prospective studies. In
      conclusion, our results validate the idea of "integrative single-case studies" as
      a new "bio-psycho-social" approach in psychoneuroimmunology. Further studies with
      SLE patients as well as with healthy probands will be necessary in order to both
      strengthen and generalize these results.

PMID- 11593456
TI  - [The competent cell - the immune system as a metaphor, sign, language and
      culture].
AB  - We investigated how the progressive function of the metaphor, the model world of
      signs, language and culture, link the cell's immunological knowledge with a
      perceivable concept of the body. Using ethnomethodologically oriented, partly
      interpretative text analysis, we examined the lymphocyte stimulation test, word
      clusters in immunology and other medical specialties, the linguistic presentation
      of the body in German, American and the internet, the presentation of the "self"
      of the cell in biology and immunology, and protocols of oncological out-patient
      interviews and chatrooms. When an abstract sign model is created, then the
      existence of a "negotiable", "competent" and "tolerant" immune cell is
      predominated by the concept of a cell and much less by elements of the body.
      Thus, the passive, spatial-anatomical concept of the body can be overcome and the
      position of the microscopically describable inner observer achieved. This is
      related to the American concept of a body that can be formed at will from
      animated individual parts. This model immune system impresses upon physical life
      and also provides a new metaphor for human interaction in accordance with the
      pattern of immunocompetent cells.

PMID- 11593457
TI  - [Psychodynamic therapy in chronic pain patients: a systematic review].
AB  - Psychoanalysis has made fundamental contributions to our understanding of
      somatoform pain disorder; however, psychodynamic therapy procedures have not been
      accorded their due recognition in the treatment of chronic pain. This is due to
      the inadequate differential indication for the employment of psychodynamic
      treatment methods, on the one hand, and to the refusal of most of the
      psychoanalysts to modify the standard psychoanalytic procedures in accordance
      with the requirements of pain treatment. This article reviews evidence of the
      modification of psychodynamic therapy procedures and their outcome in chronic
      pain patients in the context of past research. We conducted a systematic computer
      based literature research employing MEDLINE, EVIDENCE BASED MEDICINE, and PSYNDEX
      data-bases between 1980 and 2000. Psychodynamic therapy procedures are indicated
      in the first instance for patients with psychic co-morbidity and those with
      somatoform pain disorder. A modification of the psychotherapeutic technique,
      involving an approach that is more structured and is also rather supportive at
      least at the beginning, is necessary. While employing psychodynamic methods in
      the treatment of pain patients, greater importance should be attached to the
      physical level and to the 'holding function' of the therapist than is usually the
      case with the conventional psychoanalytic therapy procedures.

PMID- 11593458
TI  - [Videotape preparation of patients before hip replacement surgery improves
      mobility after three months].
AB  - Long-term follow-up investigations of the effect of psychological preparation on
      postoperative physical outcome measures have very rarely been done. In this study
      a three-month follow-up of a previous investigation of videotape preparation
      before hip replacement surgery is reported. 100 patients who previously
      participated in a randomized controlled study received physical examination and x
      ray of the hip joint three months after the operation. The mobility of the
      replaced hip joint was recorded as well as ossifications of the joint. Prepared
      patients showed a significantly higher improvement of internal rotation,
      rotational range of motion, and abduction, compared to the controls. The effect
      sizes ranged between 21% and 32% and, thus, were of clinical relevance. Prepared
      patients showed less ossifications (15%) that controls (22%), this difference was
      not significant. For the first time it could be demonstrated that psychological
      preparation before surgery can not only improve short-term and psychosocial
      outcome parameters, but also long-term physical measures. The reason for this
      effect remains to be investigated.

PMID- 11593459
TI  - [A critique of the construct "alexithymia" and its measurement--the weakness of
      self-report and the opportunities of an objective assessment approach].
AB  - Approximately thirty years ago the term alexithymia was coined but it is still
      open which characteristics have to be considered core symptoms of alexithymia. A
      selective review of recent expert definitions reveals dynamism in defining the
      alexithymia construct. At present, the self-report Toronto-Alexithymia-Scales
      (TAS) are the most frequently used measures of alexithymia. Empirical findings
      regarding various aspects of validity (factorial, concurrent, and experimental
      construct validity data) question the validity of the Toronto-Alexithymia-Scales.
      Alexithymia as measured by the TAS appears not to be consistently related to
      physiological, affect decoding or affective vigilance characteristics. The
      heterogeneity of the results could be due to the fact that non-alexithymic
      persons such as depressed or socially anxious individuals yield high scores on
      the TAS; on the other hand self-report appears to be in principle a
      methodologically inadequate approach for the assessment of alexithymia. Objective
      or direct measures of alexithymic characteristics as the Levels of Emotional
      Awareness Scale or the prototypicity analysis of mood diaries based on adjective
      checklists seem to be promising assessment methods for future research.

PMID- 11593460
TI  - [Hysterical symptoms and the body in old age].
AB  - The psychological significance of the body changes in the course of a person's
      life. Using clinical cases it was examined how conversion symptoms influence
      these changes. Elder patients having conversion symptoms hardly perceive the
      aging processes of the body. Based on the assumption that the body self develops
      in the course of a life through internalization processes and that the body
      scheme is influenced and becomes more concrete through cognitive processes (e.g.
      experiences with illness) the body self and the body scheme become increasingly
      separate. The conversion with pseudoneurological symptoms is characterized by the
      cognitively perceived body image, the body scheme, through which normally also
      the aging processes become conscious. Since the conversion requires the body
      scheme to portray psychic conflicts the somatogenic organization function (Heuft)
      is repealed and as a result the aging processes of the body and therefore aging
      are not dealt with adequately.

PMID- 11593461
TI  - [Psychobiological aspects of anorexia nervosa].
AB  - In the long term anorexia nervosa has after toxicomania the second highest
      lethality of all psychiatric disorders. The genesis of this eating disorder may
      be found in a combination of biological, cultural, familial and intrapsychic
      factors. Long-term investigations have not only verified the seriousness of the
      prognosis of lethality but have also demonstrated that depressive illness,
      compulsive behaviour and addiction quite often supersede anorexia nervosa. It
      therefore seems justified to assume biological pathomechanisms as co-factors both
      in triggering the disease as well as in the chronification of this illness.
      Besides the discussion on a genetic disposition based on results of twin- and
      family research, psychobiological models of appetite and satiation behavior based
      on known neuropeptides and neurotransmitters are presented with regard to the
      development of anorexia nervosa.

PMID- 11593462
TI  - The quick confusion scale in the ED: comparison with the mini-mental state
      examination.
AB  - The Quick Confusion Scale (QCS) is a 6-item battery of questions focusing on
      orientation, memory, and concentration weighted to yield a top score of 15.
      Analysis of the QCS compared with the Mini-Mental State Examination (MMSE) is
      needed to determine if the QCS is a valid marker of cognitive mental status. The
      MMSE and the QCS were administered to a convenience sample of 205 patients
      presenting to the emergency department. Exclusions included head trauma,
      multisystem trauma, Glasgow Coma Scale less than 15, non-English speaking,
      education level less than 8 years, contact or droplet isolation, acute illness,
      or incomplete data for reasons such as restricted patient access. Mean scores
      were 24.8(SD = 4.7; range 2-30) on the MMSE and 11.89 (SD = 3.5; range 0-15) on
      the QCS. QCS scores were significantly correlated (r = .783) with MMSE scores.
      The QCS appears comparable with the MMSE and is quicker to administer.

PMID- 11593463
TI  - Emergency physician practice and steroid use in the management of acute
      exacerbations of asthma.
AB  - This study seeks to determine patterns of emergency physician (EP) practice
      regarding steroid use in the management of acute asthma attacks in the emergency
      department (ED), and to compare practices of academic and private practice EPs.
      Two hundred eight questionnaires were mailed to academic and private practice
      EPs. The survey requested information regarding the preferred initial route (oral
      or intravenous) for steroid administration; the initial dose of steroid; the
      preferred steroid regimen for outpatient management; and whether or not inhaled
      steroids were routinely prescribed at the time of discharge. The overall response
      rate was 74%; 91% for the academic EPs and 56% for private practice EPs. Sixty
      five percent (99/143) of all EPs used the intravenous route for their initial
      dose of steroids. A significantly greater percentage of private practice EPs
      (45/58 or 78%) used intravenous steroids compared with academic EPs (54/95 or
      57%; P = .009). A total of 41% (63/153) of EPs used a tapering steroid regime for
      outpatient therapy; a significantly greater percentage (34/58 or 59%; P = .0006)
      of private practice EPs used a tapering regimen of steroids compared with
      academic EPs (29/95 or 31%). A total of 32%(31) academic and 34% (20) private
      practice EPs prescribed inhaled steroids as part of their routine discharge
      instructions. Emergency physician practice patterns regarding initial steroid
      route of administration and dose, and outpatient-dosing regimens are variable.
      Only a minority of EPs prescribe steroid metered dose inhalers as part of their
      outpatient management of asthma.

PMID- 11593464
TI  - Management of multiple burn casualties in a high volume ED without a verified
      burn unit.
AB  - The objective of the study was to evaluate the effectiveness of triage,
      treatment, and transfer interventions on multiple burn casualties managed in a
      high volume ED that does not have a verified in-hospital burn unit. The charts of
      11 male patients injured in a 1999 foundry explosion and brought to Baystate
      Medical Center (BMC), a level I trauma center, were reviewed. All patients
      sustained deep partial and full thickness burns. The injury severity score (ISS)
      ranged from 9 to 75. Five patients had total body surface area (TBSA) burns of
      10% to 50% and 6 patients had TBSA burns of 70% to 95%. Transfer times from the
      scene to BMC ranged from less than 5 minutes to 22 minutes. All 11 were initially
      triaged, resuscitated, and evaluated at BMC. Of the 9 patients transferred to
      verified burn units, 8 were intubated, 6 of 6 had negative abdominal ultrasounds,
      4 had undergone escharatomies, and 1 had undergone bronchoscopy before transfer.
      Nine critically injured burn patients with ISS of 9 to 75 were transferred from
      BMC to verified burn units. For 8 of these patients, the average time from
      triage, evaluation, and treatment to transfer was 2 hours. The ninth patient was
      initially admitted overnight then promptly transferred after re-evaluation of his
      hand burns indicated a need for more specialized care. Two of 9 transferred
      patients, both with ISS of 75 died. Although 7 other patients had prolonged and
      complex courses, none of their subsequent complications were referable to missed
      injuries from this transferring facility. The resources and expertise of a high
      volume ED without an in-hospital burn unit can be effectively used in the initial
      resuscitation and treatment of multiple burn casualties. Coordinated responses
      among emergency medicine, trauma, anesthesia, and nursing personnel are
      instrumental to the rapid triage, resuscitation, and treatment of critically
      injured burn patients. Future disaster planning should incorporate a clearly
      demarcated, ED command center led by an easily identifiable "captain of the
      ship," as well as more accurate patient identification systems and improved
      communications with family members.

PMID- 11593465
TI  - Improving emergency medical services for children with special health care needs:
      does training make a difference?
AB  - This study evaluated the impact of a paramedic training program on emergency
      medical services (EMS) responses for children with special health care needs. EMS
      responses for children with a congenital or acquired condition or a chronic
      physical or mental illness, were reviewed. Responses, related to the child's
      special health care need, involving paramedics who had completed our training
      program were compared with responses with paramedics not participating in the
      training. There was significantly more advanced life support treatment for
      responses with paramedics completing the training program compared with other
      responses. However, there was no significant difference in transport to a
      hospital or in-hospital admission between these 2 groups. This finding suggests
      that existing EMS protocols may play a more important role in emergency treatment
      and transport of children with special health care needs than specialized
      training of already certified paramedics.

PMID- 11593466
TI  - The prevalence and implications of incidental findings on ED abdominal CT scans.
AB  - We reviewed reports from 321 consecutive emergency department (ED) noncontrast,
      helical "renal stone" abdominal CT scans obtained at a single medical center
      between April 1996 to June 1997 for incidental findings. Incidental findings were
      common (45% of scans), and approximately half were rated of "moderate" or
      "serious" concern by 2 independent reviewers (kappa = 0.72). ED records indicated
      that only 21% of incidental findings were documented, and only 11 (18%) of cases
      with findings of "moderate/severe" concern had evidence of follow-up on hospital
      chart review. Although work-up of these 11 cases did not yield any serious
      diagnoses, many potentially serious incidental findings without follow-up remain
      worrisome.

PMID- 11593467
TI  - Presentation and symptom predictors of coronary heart disease in patients with
      and without diabetes.
AB  - The aims of this prospective, observational study were to compare: (1) symptom
      presentation of coronary heart disease (CHD) between patients with and without
      diabetes and (2) symptom predictors of CHD in patients with and without diabetes.
      We directly observed 528 patients with symptoms suggestive of CHD as they
      presented to the ED of a 900-bed cardiac referral center in the northeastern
      United States. There were no significant differences in symptom presentation of
      CHD between patients with and without diabetes, although patients with diabetes
      were slightly more likely to present with shortness of breath (P = .056).
      Patients with diabetes reported their symptoms to be more severe compared with
      those without diabetes (P = .036). Neck/throat pain and arm/shoulder pain were of
      borderline significance in predicting CHD in patients with diabetes (P = .059 and
      P = .052, respectively). Classic chest symptoms and diaphoresis were independent
      predictors of CHD in patients without diabetes (P = .002 and P = .049,
      respectively). The perceived severity of symptoms was not predictive of CHD in
      patients with or without diabetes. Symptoms thought to be diagnostic of CHD are
      not helpful in patients with diabetes. Future research should focus on
      identifying more useful predictors of CHD in patients with diabetes.

PMID- 11593468
TI  - Vital signs fail to correlate with hemoperitoneum from ruptured ectopic
      pregnancy.
AB  - The objective was to determine correlation between vital signs and hemoperitoneum
      in ruptured ectopic pregnancy. A retrospective chart review of ectopic
      pregnancies at our urban county hospital between 1990 and 1998 was conducted.
      Fifty-one cases met inclusion criteria. Mean minimum systolic blood pressure
      (SBP) 89mmHg (range 40-118), mean maximum heart rate (HR) 101 beats/min (range 62
      156). Mean volume of hemoperitoneum 1,050 mL (range 400-2,000 mL). Correlation
      between vital signs and volume of hemoperitoneum was poor (R(2) = 0.04 for HR,
      R(2) = 0.1 for SBP). Association of tachycardia with hypotension was also poor
      (R(2) = 0.1). Extreme individual variations were observed. If surgical decisions
      were made on the basis of hypotension, 38% of patients could have received either
      inappropriate additional studies or surgical approach. Patients with normal vital
      signs had a 20% chance of having class IV blood loss at surgery. HR and blood
      pressure do not correlate well with volumes of hemoperitoneum from ruptured
      ectopic pregnancy.

PMID- 11593469
TI  - Inhaled nitrous oxide versus placebo as an analgesic and anxiolytic adjunct to
      peripheral intravenous cannulation.
AB  - The objective was to determine whether an inhaled 50:50 mixture of nitrous oxide
      and oxygen (N(2)O/O(2)) provides significant pain and anxiety relief during
      intravenous cannulation in healthy adults. The study was conducted at the ED of a
      military teaching hospital. Participants included adult volunteers aged 18 to 50
      years. Excluded were those with allergy to N(2)O, anemia, cardiac disease,
      pregnancy, asthma, or bone marrow disorder. A prospective, randomized, double
      blind, placebo-controlled crossover design was used comparing a 50:50 mixture of
      N(2)O/O(2) versus O(2). After recording baseline nonhatched 100mm visual analog
      scales (VAS) for pain and anxiety, subjects inhaled gas 1 for 120 seconds,
      followed by antecubital intravenous cannulation, discontinuance of gas and VAS
      rating of procedural pain and anxiety. After 15 minutes, the experiment was
      repeated with gas 2. Ten subjects would detect a 12mm difference in pain or
      anxiety with a standard deviation of 10 mm, an alpha error under 0.05 and a power
      over 80%. Differences between VAS were compared by matched 2-tailed t-test.
      Eleven subjects were enrolled. One withdrew because of dizziness while inhaling
      gas (N(2)O). The 10 remaining subjects reported significantly less pain
      (N(2)O/O(2) 14.5mm, SD 18; O(2) 34.3mm, SD 23.4; P < .01) and anxiety (N(2)O/O(2)
      - 7.9mm, SD 7.8; O(2) 6.0mm, SD 11.6; P < .02) when inhaling N(2)O/O(2) than when
      inhaling O(2) alone. N(2)O/O(2) provided significant pain and anxiety reductions
      during intravenous cannulation. Some patients may experience adverse perceptions
      while using N(2)O, limiting its utility. Further studies defining the role of
      N(2)O as an anxiolytic agent, efficacy in actual patients, and cost comparisons
      with intravenous conscious analgesia/sedation, are warranted.

PMID- 11593470
TI  - Emergency management of the nonviable intrauterine pregnancy.
AB  - Fetal death early in gestation is common. Patients in the first trimester of
      pregnancy with abdominal pain or vaginal bleeding often present to the emergency
      department for care. Over the past 20 years, the technology available to confirm
      or exclude the diagnosis of a nonviable pregnancy has improved dramatically.
      These improvements have altered the diagnostic approach to these patients and
      have lead to a change in the terminology used to categorize the pregnancy status.
      In addition, the therapeutic options available to manage patients with a
      confirmed nonviable pregnancy have expanded greatly. In this article, we re
      evaluate the classification scheme used to categorize patients with first
      trimester pain or bleeding given the improved technology that is available to the
      emergency physician today. We discuss the role of ultrasound and biochemical
      markers in confirming or excluding the diagnosis of a nonviable pregnancy.
      Finally, we review the therapeutic options, including expectant, surgical as well
      as medical management that are available once the diagnosis of a nonviable
      intrauterine pregnancy has been confirmed.

PMID- 11593471
TI  - The role of alcohol in asthma: a review of clinical and experimental studies.
AB  - Asthma is among the most common ED diagnoses. Asthma exacerbations are generally
      treated by medications that cause bronchodilation and those that reduce airway
      inflammation. The effect of alcohol on asthma has been studied by investigators
      with mixed results. Some studies have reported that alcohol has a beneficial
      effect on asthma; others report worsening of symptoms. It has been suggested in
      some quarters that additives in alcoholic drinks cause bronchoconstriction and
      that pure ethanol has a salutary effect on asthma. If further research bears out
      this supposition, ethanol may play a limited therapeutic role in asthma that is
      refractory to other therapy. Emergency physicians should counsel asthmatic
      patients to avoid alcoholic beverages because they may cause an exacerbation of
      asthma.

PMID- 11593472
TI  - Prominent R wave in lead V1: electrocardiographic differential diagnosis.
AB  - Tall lead V1 (tall RV1), defined as an R/S ratio equal to or greater than 1, is
      not an infrequent occurrence in emergency department patients. This
      electrocardiographic finding exists as a normal variant in only 1% of patients.
      Physicians should therefore be familiar with the differential diagnosis for this
      important QRS configuration. The electrocardiographic entities which can present
      with this finding include right bundle branch block, left ventricular ectopy,
      right ventricular hypertrophy, acute right ventricular dilation (acute right
      heart strain), type a Wolff-Parkinson-White syndrome, posterior myocardial
      infarction, hypertrophic cardiomyopathy, progressive muscular dystrophy,
      dextrocardia, misplaced precordial leads, and normal variant. Various cases are
      presented to highlight the different causes of the tall RV1.

PMID- 11593473
TI  - Electrocardiographic manifestations of pulmonary embolism.
AB  - The electrocardiogram (ECG) may be entirely normal in the patient with pulmonary
      embolism (P/E); alternatively, any number of rhythm and/or morphologic
      abnormalities may be observed in such a patient. The abnormal ECG may deviate
      from the norm with alterations in rhythm, in conduction, in axis of the QRS
      complex, and in the morphology of the P wave, QRS complex, and ST segment/T wave.
      The electrocardiographic findings associated with PE are numerous, including
      arrhythmias (sinus tachycardia, atrial flutter, atrial fibrillation, atrial
      tachycardia, and atrial premature contractions), nonspecific ST segment/T wave
      changes, T wave inversions in the right precordial leads, rightward QRS complex
      axis shift and other axis changes, S1Q3 or S1Q3T3 pattern, right bundle branch
      block, and acute cor pulomnale. This review focuses on the ECG and the various
      abnormalities seen in the patient with PE.

PMID- 11593474
TI  - Cerebral air embolism after central venous catheterization.

PMID- 11593475
TI  - Diabetic ketoacidosis with alkalemia.

PMID- 11593476
TI  - Splenic laceration caused by chronic posttraumatic diaphragmatic hernia.

PMID- 11593477
TI  - Pneumoperitoneum, pneumoretroperitoneum, and pneumomediastinum caused by
      laryngeal fracture after multiple trauma.

PMID- 11593478
TI  - Unilateral testicular torsion in a neonate.

PMID- 11593479
TI  - Argyria in the ED.

PMID- 11593480
TI  - Sudden death from anomalous coronary artery in an 11-year-old child.

PMID- 11593481
TI  - Dilute diquat death.

PMID- 11593483
TI  - Abdominal pain and lactic acidosis with ethylene glycol poisoning.

PMID- 11593482
TI  - Renal infarction: a rare complication of cocaine abuse.

PMID- 11593484
TI  - Low dose intravenous ketamine as an analgesic: a pilot study using an
      experimental model of acute pain.

PMID- 11593485
TI  - Stenotrophomonas maltophilia meningitis - a rare cause of headache in the ED.

PMID- 11593486
TI  - Observation unit evaluation of low risk drug-related chest pain.

PMID- 11593487
TI  - Introduction: entering the era of daily hemodialysis.

PMID- 11593488
TI  - Daily hemodialysis efficiency: an analysis of solute kinetics.
AB  - Increasing the frequency of hemodialysis increases its efficiency, which causes
      the popular dialysis yardstick, single-pool Kt/V, to underestimate the dose just
      as it overestimates the dose of less frequent dialysis. The frequency dependence
      of hemodialysis can be explained by examining solute kinetics. Several factors,
      including the logarithmic fall in solute concentration and solute disequilibrium
      within the patient, account for the improved efficiency of both daily
      hemodialysis and continuous peritoneal dialysis, but to fully explain the marked
      difference in clinical targets for dosing peritoneal versus hemodialysis, one
      must go outside the realm of urea kinetics. Solutes that dialyze easily, such as
      urea, but diffuse less readily within the patient, require a 2-compartment model
      to accurately predict their concentration profiles and to measure efficiency.
      When applied to appropriately selected solutes, the model can account for the
      difference in clinical targets and can explain the failure of other indices, such
      as middle molecule clearance, eKt/V, and EKR, to account for the differences. A
      cumulative toxic effect of these relatively secluded compounds might offer a
      better explanation of uremic toxicity and an objective rationale for increasing
      dialysis frequency and time. Simplified methods for measuring the dose of
      dialysis fail when the patient is treated more often than 3 times per week, but 2
      new and independently derived methods that include parameters to account for the
      improved efficiency have been developed for measuring frequent dialysis. The new
      expressions of dose as a weekly analog of urea clearance are similar in magnitude
      and independent of frequency, giving present-day clinicians a choice of methods
      to compare 2 to 7 treatments per week. The kinetic behavior of solutes removed by
      dialysis and the new expressions of dose support the subjective improvement
      reported by patients, many of whom have embraced a transition to more frequent
      and prolonged hemodialysis.

PMID- 11593489
TI  - Hemeral (daily) hemodialysis.
AB  - Hemodialysis is generally performed 3 times per week, a treatment prescription
      not based on optimizing the physiology of the normal kidney that maintains body
      homeostasis by removing water and waste products continuously and efficiently.
      Peritoneal dialysis might be continuous but it is not efficient. Daily
      hemodialysis is both frequent and efficient and theoretically should be superior
      to other forms of dialysis for renal replacement therapy. There is again a
      growing interest in daily hemodialysis (it was originally described in 1969), and
      a number of investigators in North America and Europe are using it. As yet, there
      have been no randomized prospective studies comparing hard outcomes in patients
      dialyzed by conventional 3-times-per-week hemodialysis with those treated with
      daily hemodialysis (either short high-efficiency or long, slow nocturnal). The
      London, Ontario, study is the first attempt to obtain comparative data. It is a 3
      year study to compare daily dialysis patients with cohort controls. To date, the
      study shows that short daily dialysis does provide more dialysis based on Kt/V
      than standard therapy. However, predialysis blood urea values are not different
      because of improved nutrition (increased normalized protein from nitrogen
      appearance (nPNA) and serum albumin levels). Anemia is improved with less
      erythropoeitin usage in the study group. Phosphate control is good, but no better
      than by conventional dialysis and phosphate binders are still required unlike
      patients receiving nocturnal dialysis. Blood pressure and volume management is
      better with daily dialysis. So far, the study patients show a trend to less
      morbidity than their controls, but differences are not (as yet) statistically
      different. Blood access in daily dialysis dose not cause problems. Quality of
      life is significantly increased in a number of areas with daily dialysis. The
      economic impact of daily dialysis is not yet known; the general premise is that
      the higher dialysis costs attributable to an increment in treatments will be
      offset by increased wellness and less morbidity with the subsequent beneficial
      impact on drugs, hospitalizations, and so on. The provision of daily dialysis in
      the home has attractive economic implications. A considerable growth for this
      superior form of therapy is expected.

PMID- 11593490
TI  - Nocturnal home hemodialysis in North America.
AB  - Nocturnal home hemodialysis (NHD) was made possible in the 1960s by fail-safe
      monitoring, the Scribner shunt, and low-resistant Kiil dialyzer allowing
      hemodialysis without a blood pump. In London, Sheldon was the first to use
      overnight home hemodialysis. The Lynchburg NHD program and Lisa Murphy, a
      dietician in Bender's NHD program in Kansas City, developed a questionnaire for
      short daily hemodialysis and NHD. The questionnaire was sent to all known daily
      hemodialysis programs in North America. Some advances in nocturnal home
      hemodialysis since 1994 include: improvement in teaching methods, preventing
      disconnects and air emboli, preventing catheter infections, and using
      arteriovenous fistulas and grafts for access. As of January 2001, there were 13
      centers in North America performing daily nocturnal home hemodialysis caring for
      115 patients. Since 1997, all programs performing NHD have validated Pierratos'
      reported results, showing improvement in quality of life, better blood pressure
      control with fewer medications, reduced Epogen usage, reduced hospitalizations,
      control of phosphorous without binders, and a greater sense of hope for patients.
      Even though this new modality is safe and better for selected patients with ESRD,
      dialysis providers in Canada and the United States cannot afford to offer NHD
      within the present reimbursement scheme.

PMID- 11593491
TI  - Daily hemodialysis: a nursing perspective.
AB  - Daily hemodialysis can be performed in the center or at home for varying lengths
      of time. Short daily hemodialysis (SDHD) can be defined as one and one half- to
      three-hour treatments performed 6 days per week. Nocturnal hemodialysis (NHD) is
      performed for 6 to 10 hours, 5 to 7 nights per week. Patient selection criteria
      can range from basic requirements, such as the ability to communicate, to medical
      necessity related to comorbid conditions. Central venous catheters (CVCs), mature
      arteriovenous fistulas, and synthetic grafts have been used successfully for
      daily dialysis therapies, although documented experience with grafts is somewhat
      limited. Documented nursing issues surrounding these therapies are very limited.
      Few changes are required to adapt daily dialysis to the in-center environment.
      Patient training strategies and scheduling for the home application vary between
      institutions, but the core approaches remain the same. Daily hemodialysis
      therapies can be integrated easily into existing home hemodialysis programs with
      very little extra effort. This article discusses nursing issues and provides
      relevant information for those who are interested in incorporating daily
      hemodialysis (DHD) therapies into their program.

PMID- 11593492
TI  - Technical considerations for short daily home hemodialysis and nocturnal home
      hemodialysis.
AB  - Technical considerations for daily short home hemodialysis and nocturnal home
      hemodialysis plays an important role in the long-term success of such programs.
      The equipment must be selected based on the patient and program requirements.
      System maintenance programs and patient education procedures must be developed to
      ensure patient safety and compliance with the various standards. Technical
      staffing for these and similar programs are largely dependent on equipment
      complexity and reliability. A suggested starting point would be one technologist
      per 10 home patients. Remote treatment monitoring is optional but if decidedly
      required, providing a broad schedule of monitoring coverage is highly
      recommended, thereby allowing the patient flexibility with treatment times.

PMID- 11593493
TI  - The economics of daily dialysis.
AB  - Research suggests that daily hemodialysis improves clinical outcomes and patient
      quality of life when compared with conventional hemodialysis; however, little is
      known about its economic impact. In this article, we review the literature on the
      costs of daily hemodialysis (n = 170). We also present updated results from an
      economic model we constructed that compares 1-year treatment costs for short
      daily in-center, short daily at-home, nocturnal, and conventional hemodialysis.
      Clinical parameters for the model were drawn from our review of the clinical
      literature. Resource use during daily hemodialysis was modeled after the
      experience of 2 ongoing programs in the United States, a short daily program in
      California (n = 26) and a nocturnal program in Virginia (n = 13). Reports from
      the literature and our economic model suggest daily hemodialysis might provide
      better outcomes and savings when compared with conventional hemodialysis.
      However, larger, longer controlled studies are needed to see if daily dialysis
      fulfills these promises. We discuss several issues researchers should keep in
      mind in designing future studies about the economics of daily dialysis.

PMID- 11593494
TI  - Daily hemodialysis: a dialysis provider perspective.
AB  - Regardless of size, ownership or corporate structure, the goal of the dialysis
      provider is to deliver the best renal substitution therapy in the safest and most
      convenient manner, at a cost commensurate with reimbursement. This paper reviews
      the available data on daily hemodialysis, focusing on its ability to satisfy this
      goal. In addition, it examines the potential influence of frequency, time, and
      dose of dialysis on clinical outcomes of various series over the last 3 decades.
      The available data strongly suggest the clinical benefits of daily hemodialysis,
      but are not sufficient to show statistically better outcomes. Under the present
      reimbursement system, daily hemodialysis is not economically feasible in the
      United States. Prospective clinical trials designed to prove the benefits of
      these therapies and justify their reimbursement are needed.

PMID- 11593495
TI  - Daily hemodialysis: challenges and opportunities in the delivery and financing of
      end-stage renal disease patient care.
AB  - Daily/home hemodialysis is the latest technologic advance in the care of end
      stage renal disease (ESRD) patients, and promises improved clinical outcomes and
      quality of life. Should these benefits prove to be true, an increasing number of
      patients will be interested in this modality of care, raising challenges and
      opportunities for providers of care and payers, as well as patients themselves.
      For patients to have access to this and other new forms of technology to treat
      ESRD, it will be necessary to re-examine the current care delivery and financing
      systems and reconfigure these so that the incentives of best clinical practice
      and outcomes are properly aligned with appropriate and sensible cost constraint.

PMID- 11593496
TI  - Appointment of statistical editor and quality of statistics in a small medical
      journal.
AB  - AIM: To test if the appointment of a statistical editor improves the quality of
      manuscripts published in a small general medical journal. METHODS: Retrospective
      review of all manuscripts containing statistical data published in the Croatian
      Medical Journal between 1992 and 2000 (n=241). Statistical analysis and its
      presentation were assessed by a single observer. RESULTS: Before the appointment
      of statistical editor in 1996, 97 manuscripts with statistical data were
      published. Statistics was not satisfactory in 52 (54%) of them, including 26
      definite errors in analysis and 43 in presentation. After the appointment of
      statistical editor, 144 manuscripts containing statistical data were published.
      Statistics was not satisfactory in 91 (63%) of them, with 51 definite errors in
      analysis and 69 in presentation. Out of 144 manuscripts, the editor-in-chief sent
      out 30 (21%) for statistical review. Statistics was not satisfactory in 25 of
      them, including 11 definite errors in analysis and 17 in presentation.
      Statistical editors comments improved three manuscripts. If the authors had
      acknowledged all statistical editors suggestions, 9 more manuscripts would have
      been improved. Statistical editor had a total of 195 comments on 30 published
      manuscripts. Most numerous were the comments concerning the presentation of the
      statistical analysis (51%), followed by the general comments (26%), comments on
      analysis (11%), study design (8%), and interpretation (4%). CONCLUSION:
      Appointment of a statistical editor is not a guarantee of improvement of
      statistics in small journals. Other measures are necessary, including strict
      editorial policy on statistical review, monitoring of revised manuscript
      versions, and enrollment of formally trained biostatisticians.

PMID- 11593497
TI  - Medical migration.
AB  - The issue of professional migration, however emotional it may have become, ought
      not to be regarded in moralizing terms. The history of western medicine is the
      history of migrating physicians. A doctor who moves from a locality to another to
      take up a new assignment there cannot be said to have "abandoned his patients".
      This emotional bond has become the victim of specialization and of
      depersonalization of medical services and not of medical migration, brain drain
      or otherwise. The primary reason for medical migration is not financial; the
      desire to migrate usually begins with the desire to learn. Professionals crave in
      the first line for professional satisfaction. The migration of medical manpower
      cannot be stopped with administrative measures and will not be stopped by
      exhortations and appeals, moralization and condemnations. Brain drain is a global
      phenomenon and has always been so. A country which loses its professionals, its
      doctors, should examine the social relationships within the profession and should
      investigate whether the opportunities for deriving professional satisfaction from
      everyday work exist or whether these have been thwarted by the hierarchy,
      conservatism, cronyism and the general lack of comprehension of what good medical
      care is about.

PMID- 11593498
TI  - Endothelin mediates phospholipase C stimulation in the proximal tubule during
      initiation of compensatory renal growth in adult rats.
AB  - AIM: Mechanisms that initiate compensatory renal growth following unilateral
      nephrectomy are incompletely understood. An early event following unilateral
      nephrectomy is the activation of phospholipase C in the apical membrane of the
      proximal tubule, mediated by an unknown agonist. We tested the hypothesis that
      endothelin is responsible for the stimulation of phospholipase C in rat proximal
      tubule following unilateral nephrectomy. METHODS: Compensatory renal growth was
      induced in adult male rats by unilateral nephrectomy. 1,2-Diacylglycerol, a
      product of phospholipase C activation, was measured in renal cortical slices and
      isolated proximal tubules, respectively, 20 min following unilateral nephrectomy,
      or after incubation of the slices or proximal tubules with plasma from
      unilaterally nephrectomized or sham-operated rats. RESULTS: Twenty min following
      unilateral nephrectomy, an increase in 1,2-diacylglycerol concentration occurred
      in the renal cortex. Bosentan, a nonselective endothelin receptor antagonist, as
      well as an anti-endothelin-1 antibody administered intravenously, completely
      inhibited this 1,2-diacylglycerol accumulation in renal cortex. Incubation of
      renal cortical slices with plasma from unilaterally nephrectomized or bilaterally
      nephrectomized rats, stimulated 1,2-diacylglycerol production in isolated
      proximal tubule apical membranes. Again, bosentan prevented the increase evoked
      by incubation with plasma from unilaterally nephrectomized rats. Finally,
      concentration of endothelin-1 increased in renal cortex in response to unilateral
      nephrectomy. CONCLUSION: These results make evident the role of endothelin in
      stimulation of phospholipase C in proximal tubule following unilateral
      nephrectomy, suggesting participation of the endothelin system during the
      initiation of the compensatory renal growth.

PMID- 11593499
TI  - Relaxant effect of oxytocin on isolated human oviduct.
AB  - AIM: Oxytocin produces concentration-dependent relaxation of isolated isthmus and
      ampulla of human oviduct precontracted by histamine. The aim of our study was to
      investigate whether this oxytocin effect was specific and by which receptors it
      was mediated. METHODS: We investigated effects of oxytocin and its antagonists on
      isolated isthmus and ampulla of the uterine tubes from 20 women who underwent
      surgery for uterine fibroids. Selective vasopressin and oxytocin antagonists were
      used to treat isolated preparations of the tubes. RESULTS: In a concentration
      dependent manner, oxytocin enhanced spontaneous relaxation of both isthmus
      (EC50=1.23+/-0.03 x 10(-7) mol/L) and ampulla (EC50=1.04+/-0.26 x 10(-7) mol/L)
      precontracted by histamine. Neither predominantly selective vasopressin V1
      receptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylene-propionyl1,0
      metyr2,arg8]-vasopressin (1.0 x 10(-9)-1.0 x 10(-7) mol/L), nor predominantly
      selective vasopressin V2 antagonist, [1-(beta-mercapto-beta,beta
      cyclopentamethylene-propionic acid), 2-D-isoleucine, 4-D-isoleucine]-arginine
      vasopressin (1.0 x 10(-9)-1.0 x 10(-7) mol/L) affected significantly the
      relaxation of isolated ampulla and isthmus produced by oxytocin. On the other
      hand, [Deamino-Cys1,D-Tyr (Et)2, Thr4, Orn8]-oxytocin, a selective blocker of
      oxytocin receptors, produced in a concentration-dependent manner (6.7 x 10(-9)
      mol/L, 2.0 x 10(-8) mol/L, and 6.7 x 10(-7) mol/L) significant shifts of the
      concentration-response curves of relaxation for oxytocin to the right in isolated
      preparations of both the ampulla and the isthmus. The values of pA2 for [Deamino
      Cys1,D-Tyr (Et)2, Thr4, Orn8]-oxytocin calculated from constrained Schilds plot
      were 8.08+/-1.53 for ampulla and 7.94+/-0.67 for isthmus. CONCLUSION: Oxytocin
      relaxes smooth muscles in human oviduct through a specific effect on oxytocin
      receptors.

PMID- 11593500
TI  - Lipoprotein lipase gene polymorphism and lipid profile in patients with
      hypertriglyceridemia.
AB  - AIM: To assess lipid profile and the genotype distribution of lipoprotein lipase
      gene polymorphism at Pvu II polymorphic site within the intron between exons 6
      and 7 in patients with hypertriglyceridemia. METHODS: Pvu II polymorphism was
      determined in 116 hypertriglyceridemic patients and 50 normolipidemic controls
      from Zagreb, Croatia. DNA was extracted from peripheral blood mononuclear cells.
      Polymerase chain reaction was used for amplification of 6th intron, which was
      then restricted with Pvu II-restriction endonuclease. Serum lipid and lipoprotein
      fractions were determined by standard enzymatic methods. Cholesterol
      concentrations in HDL subfractions, HDL2 and HDL3, were determined after
      precipitation with polyethyleneglycol. Apolipoproteins (apo) A-I and B were
      determined by immunonephelometry. RESULTS: Triglycerides showed a positive
      correlation with total cholesterol (r=0.222, 95% CI=0.041-0.389, p=0.017) and
      inverse correlation with HDL-cholesterol (r= -0.278, 95% CI= -0.449 to -0.088,
      p=0.005), especially with HDL3-cholesterol (r= -0.333, 95% CI= -0.497 to -0.147,
      p=0.001). The respective frequencies for genotypes /, +/, and +/+ were 22, 58,
      and 36 in the patient group, and 17, 17, and 16 in the control group. Serum
      triglycerides in the patient group, expressed as median in mmol/L, were 3.30
      (range, 2.60-10.90), 3.60 (range, 2.50-21.50), and 3.99 (range, 2.50-15.56),
      respectively. Serum concentration of triglycerides differed significantly between
      the +/+ and / genotype (p=0.043). CONCLUSION: There is an association between
      genetic variation at the locus for lipoprotein lipase and high serum triglyceride
      levels. This might prove useful in the detection of individuals susceptible to
      the development of hypertriglyceridemia, as well as a marker in the analysis of
      this genetic defect in patient families.

PMID- 11593501
TI  - AlphaB-crystallin expression in celiac disease - a preliminary study.
AB  - AIM: To investigate immunohistochemically alphaB-crystallin expression and
      distribution in biopsy sections of the small intestine of patients with celiac
      disease, and the relationship, if there is any, between the expression of this
      heat shock protein and the degree of mucosal atrophy. METHODS: Biopsy specimens
      of 22 subjects (12 celiac patients and 10 "normal" individuals) were investigated
      by immunoperoxidase screening procedures using monoclonal antibodies to detect
      the presence of alphaB-crystallin. Sections from each case were stained with
      hematoxylin and eosin to assess mucosal morphology. RESULTS: The epithelial cells
      of the small intestine stained more intensively for alphaB-crystallin in patients
      with celiac disease than in "normal" patients. The quantity and degree of
      intensity of immunohistochemically demonstrable alphaB-crystallin and its
      intracellular distribution in the duodenal mucosa of the patients with celiac
      disease were closely related to the degree of villus atrophy. There was a strong
      correlation between the number of patients with celiac disease and percentage
      staining score of alphaB-crystallin per total score (Pearson's r = 0.754, p =
      0.123). The mean percentage score per total score was 20% among the patients with
      celiac disease. On the other hand, there was a weak negative correlation between
      the number of normal controls and percentage score per total score (Pearson's r= 
      0.126, p = 0.437). The mean percentage score per total score was 4.6% among the
      normal controls. AlphaB-crystallin stained the supra-nuclear region of the
      enterocytes with a 75% sensitivity and 71% specificity. CONCLUSION: AlphaB
      crystallin, a stress response protein, is expressed in the small intestinal
      mucosa of patients with celiac disease, and the degree of mucosal atrophy
      compares significantly with the intensity of expression of alphaB-crystallin. We
      therefore conclude that an inappropriate stress response involving this heat
      shock protein within the mucosa itself may be crucial as an initiating event in
      the architectural derangement of the mucosal damage associated with celiac
      disease.

PMID- 11593502
TI  - Hand transplantation follow-up.

PMID- 11593503
TI  - Screening recommendation for women taking tamoxifen.

PMID- 11593505
TI  - Development of a universal immunoenzyme quantitative assay for detecting
      amplified products of nucleic acid and its preliminary application in hepatitis C
      virus.
AB  - OBJECTIVE: To develop a universal quantitative immunoenzyme assay (EIA) for
      detecting amplified products of nucleic acid and its application in hepatitis C
      virus (HCV). METHODS: The appropriate cycle number of amplification was selected
      to stop polymerase chain reaction (PCR) before the "plateau stage". At the same
      time, primers HCV (3) of the second PCR were modified with biotin so that the
      amplified products were labeled. The products were diluted and subsequently added
      to the streptavidin-coated wells, and the biotinylated products were captured,
      followed by denaturation of NaOH, and non-biotinylated strands were removed.
      Hybridization was performed by adding the specific probe labeled with
      fluorescein. Finally antifluorescein horse radish peroxidase (HRP) conjugates
      were added, after washing, 3, 3', 5, 5',-tetramethylbenzidine (TMB) was added to
      the wells and then measured on a microplate reader. RESULTS: EIA detection of
      amplified products of HCV showed that this assay was rapid, sensitive, specific
      and accurate. Correlation between the initial number of viral template and the
      EIA of amplified products was good. We also prospectively investigated the
      response to interferon in five patients with HCV coinfection. Results showed that
      this assay could be used as a guidance to the clinical therapy in directing the
      use of antiviral drugs. CONCLUSIONS: This assay could be widely used as a
      universal technique for the quantitative detection of amplified products of all
      nucleic acid (such as virus, bacterium) and other human genes (such as HLA B27),
      it has vast vistas.

PMID- 11593504
TI  - A randomized double-blind placebo-controlled study of lamivudine in the treatment
      of patients with chronic hepatitis B virus infection.
AB  - OBJECTIVE: To evaluate the effect of lamivudine on the loss of serum hepatitis B
      virus (HBV) DNA, HBeAg/antiHBe seroconversion and ALT levels in chronic hepatitis
      B patients and its safety profile and tolerance compared with placebo. METHODS:
      Four hundred and twenty-nine patients with chronic HBV infection as defined by
      positive HBsAg, HBeAg and HBV DNA were enrolled and randomized into lamivudine
      and placebo groups. Three hundred and twenty-two patients received lamivudine 100
      mg daily and 107 patients received placebo treatment for 12 weeks. Then, all
      patients were offered a further 9-month open label lamivudine treatment. The
      efficacy and safety were evaluated with clinical, biochemical, hematological and
      virological parameters. RESULTS: During the 12-week treatment period, 92.2% of
      lamivudine treated patients became HBV DNA negative (below 1.6 pg/ml) compared
      with only 14.1% of those receiving placebo (P < 0.01). At the end of 12 week, the
      sustained negative rate for HBV DNA in the lamivudine treated group was 78.5%
      compared with the placebo group (11.1%; P < 0.01). There was a trend to a high
      proportion of patients treated with lamivudine to lose HBeAg (8.1%) and develop
      antiHBe (10.2%) than treated with placebo (5.3% and 6.4% respectively), but this
      difference was not statistically significant. Patients with elevated ALT levels
      at baseline became normal in 60. 3% of the lamivudine treated group compared with
      the placebo group where only 27.5% were normal (P < 0.01). Lamivudine was well
      tolerated in a dose of (100 mg daily) and the overall incidence of adverse events
      was similar to that of the placebo. CONCLUSIONS: Lamivudine (100 mg daily) is
      very effective in the inhibition of HBV replication, indicated by the rapid loss
      of serum HBV DNA, and often accompanied by a decrease of serum ALT levels.
      Lamivudine is well tolerated without severe adverse events during treatment.

PMID- 11593506
TI  - Study on vertical transmission of Chlamydia trachomatis using PCR and DNA
      sequencing.
AB  - OBJECTIVE: To investigate the vertical transmission rate of Chlamydia trachomatis
      (CT) in Chongqing, China. METHODS: Specimens taken from 278 women and from their
      79 infants were examined by cell culture, polymerase chain reaction (PCR) and DNA
      sequence analysis. Chlamydia trachomatis was isolated in McCoy cell culture. CT
      DNA was extracted with a modified Nal method. After cloning, recombinant plasmids
      were used for sequence analysis with the dideoxy chain termination method.
      RESULTS: 10.8% (30/278) of the cervical cultures of pregnant women were positive
      for Chlamydia trachomatis, while the positive rate tested by PCR was 14.0%
      (39/278). The vertical transmission rate of Chlamydia trachomatis was 55.0%
      (11/20). The incidences of conjunctivitis and pneumonia in infants with Chlamydia
      trachomatis positive mothers were 27.3% and 18.2%, respectively. DNA sequences of
      Chlamydia trachomatis isolated from the cervix of a mother and the nasopharynx of
      her baby were identical. CONCLUSION: Chlamydia trachomatis infection is quite
      common in Chongqing, China. Our report is the first report of CT vertical
      transmission proved by DNA sequence analysis.

PMID- 11593507
TI  - Relationship of vascular remodeling and restenosis after interventional therapy:
      an experimental study on rabbit atherosclerotic iliac artery model.
AB  - OBJECTIVE: To evaluate the relative contribution of every part of vascular wall
      to lumen area loss after angioplasty. METHODS: Angioplasty was performed on
      rabbits iliac atherosclerosis model. Histomorphometric results of histological
      cross-sectional areas from target vessels of animals killed immediately after
      angioplasty (acute group, n = 20) were compared with those of the same areas from
      animals killed 4 weeks after the procedure (chronic group, n = 23), when
      restenosis occurred in this model. If taking 30% diameter decrease as restenosis
      criteria, the chronic group was further divided into two subgroups (nonrestenosis
      subgroup [NRS, n = 9] and restenosis subgroup [RS, n = 14]) and their
      histomorphometric results were also compared. RESULTS: The lumen area decreased
      by 0.48 mm2 from acute group to chronic group (acute group 0.86 +/- 0.23 mm2 vs
      chronic group 0.38 +/- 0.20 mm2, P < 0.001). Over the same period intimal area
      increased by 0.12 mm2 and the area circumscribed by inner elastic lamina (IEL
      area) decreased by 0.36 mm2. Intimal hyperplasia could only explain 25% of the
      later lumen area loss. We further found a more significant IEL area decrease in
      RS subgroup than in NRS subgroup (0.68 +/- 0.35 mm2 vs 0.94 +/- 0.14 mm2, P <
      0.05), despite the same intimal area (0.39 +/- 0.16 mm2 vs 0.41 +/- 0.31 mm2, P =
      NS). The different lumen area between RS subgroup and NRS subgroup (0.27 +/- 0.10
      mm2 vs 0.55 +/- 0.10 mm2, P < 0.001) was predominantly due to the greater IEL
      shrinking in RS subgroup. CONCLUSION: Our data indicate that later lumen area
      loss after angioplasty results from both intimal hyperplasia and arterial
      shrinking (remodeling), but the latter plays a much greater role.

PMID- 11593508
TI  - Studies on renin-2 gene in transgenic rats.
AB  - OBJECTIVE: To determine the function of, in vivo, renin and its role in the
      pathogenesis of hypertension. METHODS: A renin-2 gene restriction map was
      constructed by endonuclease digestion and Southern blotting hybridization.
      Transgenic rats were produced via microinjection method. RESULTS: The 24 kb
      fragments containing mouse full-length ren-2 and its flanking sequence were
      cleaved by single enzymes (EcoR I, Kpn I and BamH I) and combined enzymes (EcoR
      I/Kpn I, Kpn I/BamH I and BamH I/EcoR I), respectively. The digests were
      electrophoresed in 0.8% agarose plates and transferred onto NC membranes.
      Radioactive 735 bp and 1400 bp probes obtained from half and full-length renin-1
      cDNA were used in southern blotting hybridization. According to the
      electrophoresis and hybridization patterns, a ren-2 restriction map was
      constructed. 1603 fertilized rat ova after injection with purified 24 kb renin-2
      gene were implanted into the oviducts of 81 pseudopregnant recipients in about 20
      ova per female rat. 306 progenies were obtained from 50 foster mothers (average
      of pregnancies was 56.6%). 248 survived pups were identified by PCR analysis and
      Southern hybridization, and eight positive rats were found to be the transgenic
      rats (founder, F). All of them carried long fragments (24 kb) of renin-2 gene
      with normal blood pressure. Preliminary breeding and screening were carried out
      in the founder. Total survival pups (17.8%) and overall efficiencies (1%) were
      harvested as the same as those reported in the literatures. A systemic
      observation and the problems occurred during production of transgenic rats were
      also described besides the technique procedure used in this study. CONCLUSIONS:
      Mapping of full-length murine ren-2 can be used in investigation of the structure
      and function of the gene. The results denoted that the ren-2 transgenic rats were
      successfully established in this study and the technique used in the production
      of transgenic rats was proved to be valid in leading to wide-spread application
      of transgenic technique to many other related researches.

PMID- 11593509
TI  - An animal and clinical study on the change of neuropeptide Y release evoked by
      electrical stimulation and myocardial ischemia.
AB  - OBJECTIVE: To investigate the change characteristics of neuropeptide Y (NPY)
      release during acute myocardial ischemia period. METHODS: The animal test was
      carried out in in situ perfused guinea pig hearts with intact sympathetic
      innervation. Electrical stimulation-evoked exocytotic release of NPY during
      ischemia and reperfusion was tested by radioimmunoassay (RIA). The plasma NPY
      concentrations were measured in patients with acute myocardial infarction (AMI)
      and angina pectoris (AP) in different times. RESULTS: Electric stimulation of the
      left ganglion in guinea pig heart evoked an exocytic release of neuropeptide Y.
      Stimulation after 20 minutes of global ischemia (S2), compared with control
      period stimulation (S1) produced the inhibition of NPY to a certain extent
      (S2/S1: 0.72, P < 0.05), whereas the inhibition of NPY release disappeared after
      5 minutes reperfusion (with S2/S1 of 1.01, P > 0.05). Ischemia alone, without the
      electric stimulation, did not apparently induce NPY release. The clinical test
      found that the plasma NPY level was increased significantly during the acute
      ischemia attack period of coronary heart disease (CHD). The plasma NPY level
      reached peak (136.3 +/- 66.5 pg/ml) in patients during the first day after AMI.
      It began to decrease from the third day and came to normal level in the end of
      the first week. The plasma NPY level was 159.3 +/- 98.5 pg/ml in AP patients
      during angina attack. After two weeks treatment, the plasma NPY level was
      decreased to 118.9 +/- 54.3 pg/ml (P < 0.05). CONCLUSIONS: The NPY release of
      global ischemia have some relation with sympathetic nerve activity. At the early
      stage of ischemia, NPY release is inhibited to some degree and the inhibition
      factors will fade away on reperfusion. NPY interferes with the pathogenesis and
      the pathophysiolgy.

PMID- 11593510
TI  - Aldosterone biosynthesis in extraadrenal tissues.
AB  - OBJECTIVE: To determine whether extraadrenal tissues synthesize aldosterone in
      addition to vascular tissue and brain. METHODS: Ex vivo kidney perfusion was
      performed in normal Wistar rats, ACEI pretreated and adrenalectomized rats prior
      to the perfusion experiment. After equilibration for 30 minutes, 120 ml of
      perfusate was collected and subjected to reverse-phase HPLC and then aldosterone
      was measured by RIA. By RT-PCR and Southern blot the expression of aldosterone
      synthase gene-CYP11B2 mRNA was studied in both kidney tissue and cultured renal
      tubular epithelial cell, lung and liver tissues. In situ hybridization was used
      to identify the cell types of liver and lung expressing CYP11B2 mRNA. RESULTS:
      Production of aldosterone in the kidney perfusate was not changed in
      adrenalectomized rats although it was decreased in the group pretreated with ACEI
      perindopril. By RT-PCR and Southern blot the expression of CYP11B2 mRNA was
      demonstrated in both kidney tissue and cultured renal tubular epithelial cell. We
      have also identified CYP11B2 mRNA expression in liver and lung of rats. In situ
      hybridization showed that CYP11B2 mRNA was localized in the endoplasm of liver
      fat-storing cell (Ito cells) and type II alveolar cells of lung. CONCLUSIONS:
      These studies prove that kidney, liver and lung are able to produce aldosterone.

PMID- 11593511
TI  - PCR assay for the inversion causing severe Hemophilia A and its application.
AB  - OBJECTIVE: To develop a new technique based on long distance polymerase chain
      reaction (LD-PCR) to replace Southern blotting method to detect Factor VIII
      (FVIII) gene inversion leading to severe Hemophilia A (HA) and carrier. METHODS:
      Four primers P, Q, A&B were designed and synthesized. P&Q is specific for 5' and
      3' flanking regions of F8A1 respectively. A&B is specific for 5' and 3' flanking
      regions of F8A2/F8A3 respectively. LD-PCR with 3 primers and 3 temprature was set
      up, optimized and used to detect the inversion. RESULTS: The LD-PCR with primers
      P, Q, A&B, P, Q&B and P, Q&A can be used to detect the gene inversion and
      discriminate carrier from wild type. A blind analysis of 53 DNA samples from HA
      families was carried out by the LD-PCR and Southern blotting respectively. Two
      sets of the results were completely identical. They were 23 cases of inversion,
      27 cases of wild type and 3 cases of carriers. The sensitivity and specificity of
      LD-PCR are both 100%. Three inversion hemizygotes and 4 female carriers were
      identified from 5 HA families by the LD-PCR technology. CONCLUSIONS: The LD-PCR
      with primer P, Q&B or P, Q, A&B can be used to detect the gene inversion and the
      carrier of inversion. Compared with Southern blotting, this technique is simple,
      rapid, inexpensive, more sensitive, accurate and non-isotopic.

PMID- 11593512
TI  - Effects of ischemic preconditioning on reperfusion arrhythmias and
      electrophysiology in isolated rat hearts: it is not a role of KATP(+) channels.
AB  - OBJECTIVE: To investigate the effects of ischemic preconditioning (PC) and ATP
      sensitive K+ channels (KATP(+) opener nicorandil on reperfusion arrhythmias and
      electrophysiology. METHODS: Langendorff-perfused rat hearts were subjected to
      ischemic PC with three cycles of 2 minutes of global ischemia or infusion of
      KATP(+) opener nicorandil with subsequent 5 minutes global ischemia and
      reperfusion. The incidence of reperfusion arrhythmias, ventricular fibrillation
      threshold (VFT), effective refractory period (ERP) and monophasic action
      potential duration (MAPD) of the left and right ventricles were compared to those
      from control rat hearts. RESULTS: The results indicated that PC reduced the
      incidence of total arrhythmias and ventricular fibrillation during reperfusion (P
      < 0.05, vs controls). PC markedly delayed the onset of arrhythmia after
      reperfusion (P < 0.01, vs controls). PC significantly enhanced the VFT values
      during reperfusion and shortened the ERP and the MAPD during ischemia. VFT was
      restored more rapidly than that in controls. KATP+ opener nicorandil neither
      reduced the incidence of total arrhythmias and VF nor delayed arrhythmia onset.
      Nicorandil shortened ERP and MAPD90 without enhancing the VFT values, and VFT
      returned to normal as slowly as that in controls. CONCLUSIONS: We conclude that
      PC protects the globally ischemic rat hearts from reperfusion arrhythmias. The
      antiarrhythmic effect of PC is likely to be related to a significant increase of
      VFT. KATP(+) opener nicorandil has no potential antiarrhythmic action and KATP(+)
      channels may not play a major role in the antiarrhythmic effects of ischemic PC
      in isolated rat hearts.

PMID- 11593513
TI  - Hepatic radioembolization with Yttrium-90 glass microspheres for treatment of
      primary liver cancer.
AB  - OBJECTIVE: To study the clinical results of hepatic radioembolization with
      Yttrium-90 (90Y) glass microspheres in the treatment of primary liver cancer.
      METHODS: Seventeen patients with liver cancer were treated with glass
      microspheres from August 1996 to May 1998. Hepatic radioembolization with 90Y and
      lipiodol-ultrafluid was used. Percutaneous port-catheter system (PCS)
      implantations via femoral artery were performed in 12 patients. RESULTS: In the
      17 patients, their mean ratio of absorbed doses between tumor and normal liver
      was 2.4:1. CT showed a significant reduction in tumor size in 11 of the 17
      patients. Average survival was 19.5 months. The indwelling catheters of all the
      12 patients were patent and no catheter tip locations were found. CONCLUSIONS:
      90Y glass microsphere is one of the best radioisotopes. Not only good responses
      to the therapy of 90Y glass microspheres can be achieved in patients with
      metastatic liver cancer, but also in those with primary liver cancer, specially
      the localized or hypervascular mass. The patients with massive arterioportal
      shunt should not be limited to this form of radiation therapy. The percutaneous
      PCS implantation via the femoral artery is a new passageway for the treatment of
      primary liver cancer with 90Y glass microspheres and other interventional
      therapy.

PMID- 11593514
TI  - Endovascular embolization of traumatic carotid cavernous fistulas.
AB  - OBJECTIVE: To analyze the effectiveness of endovascular embolization on treatment
      of traumatic carotid-cavernous fistula (TCCF). METHODS: From 1986 to 1997, 482
      cases of traumatic carotid-cavernous fistula were treated by endovascular
      embolization in the Beijing Neurosurgical Institute. Several kinds of balloon
      catheter were used for embolization. External carotid-cavernous fistulas and rare
      carotid-cavernous fistulas (CCF) with minute leakage were treated by
      cyanoacrylate or coils. Although artery approach was applied in most cases (477
      cases), vein approach showed its own advantages in some special cases. RESULTS:
      We found a special "bileakage sign" indicating multileakage of TCCF, which was
      never mentioned before. All 482 cases were embolized successfully, and 405 cases
      maintained the patency of internal carotid artery (ICA). No treatment-related
      deaths occurred and the symptoms and signs of 462 cases were relieved after
      embolization. Emergency embolization was needed in some conditions such as
      serious epistaxis, delayed or repeated subdural hematoma, and rapid visual
      impairment. CONCLUSION: Endovascular embolization of TCCF is a safe and efficient
      method. Carefully selected operation time, operative approach, and materials are
      the essential factors to reach a best result.

PMID- 11593515
TI  - Minimally modified low-density lipoprotein induces monocyte chemotactic protein-1
      expression in vivo and a novel model for monocyte adhesion to arterial intima.
AB  - OBJECTIVE: To test whether minimally modified low-density lipoprotein (MM-LDL)
      can stimulate the arterial cells expressing MCP-1 in vivo and thus induce
      monocyte adherence to endothelium. METHODS: An animal model was constructed to
      study the function of MM-LDL in vivo. MM-LDL (600 micrograms/ml) was perfused
      into a segment of the femoral artery of rabbits (both ends of which were occluded
      with removable ligatures). After exposure to MM-LDL for 2 h, the arterial
      segments were taken out 6 or 18 h later. The arteries were subjected to in situ
      hybridization with 35S-labeled antisense monocyte chemotactic protein-1 (MCP-1)
      RNA probe and processed for scanning electron microscopy. RESULTS: The expression
      of MCP-1 mRNA of the arterial endothelial cells and smooth muscle cells were
      increased by 60% and 90% 6 h after perfusion and had a 3.2 folds and 1.6 folds
      increase 18 h after perfusion respectively as compared with control (arteries
      perfused with saline). There was also apparent monocyte adherence to the
      endothelium observed by scanning electron microscopy. CONCLUSION: MM-LDL can
      stimulate vascular cells in expressing MCP-1 mRNA and enhance monocyte adherence
      to endothelium in vivo.

PMID- 11593516
TI  - Effect of cytokines on in vitro bone resorption by cells isolated from giant cell
      tumor of bone.
AB  - OBJECTIVE: To investigate the effect of cytokines on in vitro bone resorption by
      cells isolated from giant cell tumor of bone. METHODS: Mononuclear stromal cells
      and multinucleated giant cells (MGC) were isolated from 11 cases of giant cell
      tumor of bone (GCT) and their bone resorption capability in an in vitro cell-bone
      resorption model were tested. Expressions of some cytokines were detected by
      immunohistochemistry, Western blotting analysis and Enzyme-linked immunoabsorbent
      assay (ELISA) in the GCT. RESULTS: The results showed that MGCs of GCT had
      capability to resorb bone matrix directly. Fibroblast-like stromal cells (FC)
      could not only resorb bone matrix directly, but also secret unknown factors to
      facilitate bone resorption of MGC. Exogenous TNF-alpha could significantly
      increase the bone resorption by both kinds of stromal cells, while exogenous IL-1
      did not. Expression rate of M-CSF and level of TNF-alpha in GCT were higher than
      in osteosarcoma and normal serum. CONCLUSIONS: The characteristic bone resorption
      behavior of GCT might be caused by its three major cell components. The M-CSF and
      TNF-alpha could promote their bone resorption capability.

PMID- 11593517
TI  - Effects of nerve growth factor on nitric oxide-mediated neurotoxicity in primary
      cortical cultures.
AB  - OBJECTIVE: To observe the effects of nerve growth factor (NGF) on nitric oxide
      (NO) release and constitutive nitric oxide synthase (cNOS) gene expression in
      oxygen/glucose deprived cortical neuron cultures. METHODS: Neuron viability was
      measured to assay NGF effect. The content of NO and the expression of cNOS mRNA
      were determined by spectrofluorometric method and Northern blot respectively.
      RESULTS: There were a marked increase of neuronal death and NO release in
      oxygen/glucose deprived cultures for 24 h. NOS inhibitor, NG-nitro-L-arginine
      methyl ester (NAME) 100 mumol.L-1 and NGF 50, 100 micrograms.L-1, significantly
      increased neuronal surviving and decreased NO release. However, NGF (50, 100
      micrograms.L-1) had no significant effects on neurotoxicity induced by sodium
      nitroprusside (SNP) 300 mumol.L-1 in cortical cultures. Hemoglobin (Hb), which
      binds NO, completely prevented hypoxia/hypoglycemia- or SNP-induced cell death
      and NO release at 500 mumol.L-1. NGF 100 micrograms.L-1 significantly attenuated
      cNOS gene expression. CONCLUSION: NO can mediate the neurotoxicity of
      hypoxia/hypoglycemia, and NGF can protect cortical neurons against oxygen/glucose
      deprivation-induced toxicity via inhibiting the activity of cNOS and suppressing
      the release of NO.

PMID- 11593518
TI  - Dietary L-arginine attenuates expression of vascular cell adhesion molecule-1 in
      the aortae of hypercholesterolemic rats.
AB  - OBJECTIVE: To determine whether the antiatherogenic effect of L-arginine is due
      to an inhibition of vascular cell adhesion molecule-1 (VCAM-1) expression in the
      aortae of hypercholesterolemic rats. METHODS: Twenty-four male Wistar rats were
      randomized into three groups: Group NC with normal diet (NC, n = 8), Group CC
      with 4% cholesterol and 1% cholic acid diet (CC, n = 8), Group AC with 4%
      cholesterol and 1% cholic acid diet supplemented with 3% L-arginine HCl in the
      drinking water (AC, n = 8). Eight weeks later, the blood samples were collected
      for biochemical studies, and the aortae were harvested for RT-PCR and
      immunohistochemical studies. RESULTS: The results showed that dietary L-arginine
      supplementation reduced expression of VCAM-1 in protein level and mRNA level.
      CONCLUSION: Inhibitory effect of dietary supplementation of L-arginine on VCAM-1
      expression may be one of the mechanisms of its antiatherosclerosis.

PMID- 11593519
TI  - Mechanical and histological analysis of bone-pedicle screw interface in vivo:
      titanium versus stainless steel.
AB  - OBJECTIVE: To investigate the differences in bone interface between titanium and
      stainless steel pedicle screws in the lumbar spine. METHODS: Eighteen adult mini
      pigs that underwent total laminectomy, posterolateral spinal fusion (L4-L5) were
      randomly selected to receive stainless steel (9) or titanium pedicle screw
      devices (9). In both groups, the devices were CCD (Sofamore Danek) type with the
      same size and shape. The postoperative observation time was 3 months. Screws from
      L4 were harvested along their long axis of pedicle for histomorphometric study.
      Bone-screw interface and bone volume from thread were examined using linear
      intercept techniques. Mechanical testing (torsional test and pull-out test) was
      performed on the screws from L5. RESULTS: The titanium screw group had a
      significantly higher maximum torque (P < 0.05) and angle related stiffness (P <
      0.05) measured by torsional test. In the pull-out tests, no differences were
      found between the two groups in relation to the maximum load, stiffness and
      energy to failure. Direct bone contact with the screw in percentage was 29.4% for
      stainless steel and 43.8% for titanium (P < 0.05). No differences in the bone
      purchase between the vertebral body part and pedicle part were found. CONCLUSION:
      Pedicle screws made of titanium have a better bone-screw interface binding than
      screws made of stainless steel. Torsional tests are more informative for bone
      screw interface study. Pull-out tests seem less valuable when comparing bone
      purchase of screws made from different materials.

PMID- 11593520
TI  - Clinicopathologic, immunophenotypic and ultrastructrual analyses of ATLL patients
      with cutaneous involvement.
AB  - OBJECTIVE: To study 4 cases of adult T-cell leukemia/lymphoma (ATLL) associated
      with cutaneous lesions for clinicopathology, immunophenotype, human T-cell
      leukemia/lymphoma virus type I (HTLV-I) provirus DNA and their ultrastructure. At
      the same time, HTLV-I provirus DNA of ATLL patients were also compared with 18
      cases of cutaneous lymphoma (CL), two cases of actinic reticuloid as well as two
      cases of lymphocytic infiltration. METHODS: Immunohistochemistry studies were
      carried out on the infiltrating cells using monoclonal antibodies against CD45
      RO, CD20, CD68 on paraffin-embedded sections by ABC method and using monoclonal
      antibodies against CD3, CD4 and CD8 with indirect immunofluorescence (IIF) on
      frozen sections. Skin biopsies were examined by electron microscope. Serum and
      bone marrow cells were tested for antibodies against HTLV-I-associated antigen by
      IIF, and HTLV-I provirus DNA was examined by PCR method. RESULTS: The research
      showed four patients with ATLL manifesting cutaneous lesions, were subsequently
      found with additional systemic symptoms, as extensively enlarged superficial
      lymph node, abnormal increased IL-2 receptor, flower-like cells in their
      peripheral blood and marrow. The HTLV-I provirus DNA was positive in the
      peripheral blood, bone marrow, cutaneous lesions and lymph node biopsy specimens
      by using PCR amplification of specific HTLV-I fragment while 18 cases of the CL
      were negative for HTLV-I. The special ultrastructure of skin lesions was also
      found in ATLL patients. CONCLUSIONS: The cutaneous involvement in ATLL is a type
      of cutaneous T cell lymphoma (CTCL) but shows some differential immunological
      markers for differential diagnosis. The examination of HTLV-I antibodies or HTLV
      I provirus DNA is necessary for diagnosis of ATLL. The ultrastructural
      characteristics in skin lesions of ATLL were of atypical lymphocytes and
      mononuclear cells invading the epidermis, and the mononuclear cells are
      possessing the phagocytic function and phagocytizing the degenerated epidermic
      cells or lymphocytes.

PMID- 11593521
TI  - Resistant mechanisms of Candida albicans to fluconazole.
AB  - OBJECTIVE: To detect the resistant mechanisms of Candida albicans to fluconazole
      (FCZ) at molecular biology level, since the resistance mechanisms of azole
      antifungal agents have been the focus of attention these years. METHODS: Thirty
      two FCZ-resistant C. albicans were selected as our test strains (MICs > or = 64
      micrograms/ml). With 14-alpha-demethylase gene (ERG16 gene, target enzyme
      encoding gene of azoles) as our object, we chose six sets of primers from the
      ERG16 gene to amplify the interested fragments, and conducted Southern blot
      hybridization, restriction fragment length polymorphism (RFLP), and single strand
      conformation polymorphism (SSCP) analysis for the fragments which were amplified
      by the six sets of primers, and pre-resistant sensitive strains were used as
      controls. Three representative fragments, A66, D66 and E78, were selected to be
      cloned and sequenced. RESULTS: The polymerase chain reaction (PCR) amplification
      showed that several tested strains were negative for some primers. However, our
      Southern blot analysis reminded that their resistance did not result from the
      lack of target enzyme coding gene. SSCP analysis showed that differences were
      noted between the resistant and sensitive strains and inter-resistant strains.
      Statistical analysis showed that the most variable sequence lied in the amplifier
      of the sixth pair of primer, and all the tested 32 strains showed positive
      results. In the 11 mutation points we found, five resulted in amino acid
      alterations. It is likely that one or more mutational alterations (alone or in
      combination) might lead to the expression of an enzyme highly resistant to the
      inhibitory action of FCZ which in turn is responsible for the FCZ resistant trait
      in these strains. CONCLUSION: One or more mutational alterations might lead to
      the azole resistant trait in this strains.

PMID- 11593522
TI  - Epidemiological progresses of hemorrhagic fever with renal syndrome in China.
AB  - PURPOSE: To summarize the major achievements of Chinese work on the epidemiology
      and prevention of hemorrhagic fever with renal syndrome (HFRS) in recent years,
      and to give a general review on the present situation of HFRS in China. DATA
      SOURCES: Reviews and papers published in Chinese journals, relevant to the
      objectives, written or collected by the author; and the research work of the
      author. STUDY SELECTION: An outline was drafted according to the purpose given
      above, and the relevant materials and data were grouped together into different
      items outlined. DATA EXTRACTION: All the materials and data extracted were
      published or specially assessed. RESULTS: HFRS was first recognized in the
      northeastern China in 1931. It has been found prevalent also in many other parts
      of China since 1955, and presently, 28 out of 31 provinces (autonomous regions,
      or municipalities) have been proved to be its endemic areas. The total number of
      cases is 1,256,431 from 1950 to 1997, with 44,304 death (3.53%). 50-100 thousands
      of cases could be registered annually since 1981 when the presence of the Rattus
      type HFRS was first identified serologically in China, with the highest peak in
      1986 (115,985 cases). Three types of endemicity have been differentiated: the
      Apodemus-type, the Rattus-type and the mixed type of the two, by their peculiar
      seasonal distributions of cases and by methods of serotyping (HI, MAbs serotyping
      kits). The epidemiologic features of the Rattus-type HFRS are quite different
      from that of the Apodemus-type. 67 species of vertebrates were found to harbor
      hantavirus antigen or antibodies, but the chief or primary reservoir hosts are
      Apodemus agrarius and Rattus norvegicus only. Besides the commonly recognized
      enzootic mode of transmission (via contacts with the reservoir rodents or their
      excreta), mite transmission (including certain species of gamasid mites, and
      chigger mites) has been identified as the potential vectors and reservoir hosts
      with HFRS. Vertical transmission had been found in pregnant patients with HFRS,
      and in all three chief host rodents (Apodemus agrarius, Rattus norvegicus, the
      laboratory rats). The relatively high inapparent infection rates in the
      population of endemic areas of the Rattus-type HFRS after big outbreaks (8%-20%)
      are suggested to play a significant role in the gradual decline of the incidence
      of HFRS in that areas. Three kinds of inactivated vaccines against HFRS (the
      golden hamster kidney cell vaccine, the Mongolian gerbil kidney cell vaccine and
      the purified suckling mouse brain vaccine) have been successively developed and
      proved highly effective in the prevention of HFRS. CONCLUSION: Chinese workers on
      the epidemiology and prevention of HFRS in China have accomplished great
      achievements since 1981. As the relatively high annual incidence of HFRS
      sustained in recent years, control measures have to be reinforced. Many problems
      of HFRS and hantavirus infections are still not well understood or unclear, such
      as the poly-host nature, and the multi-modes of transmission, the natural history
      of hantaviruses and their genetic variation occurred in nature etc. The task for
      effective control of HFRS and the research on its epidemiology in China should be
      held on a high priority.

PMID- 11593523
TI  - Endocarditis caused by Stenotrophomonas maltophilia.

PMID- 11593524
TI  - Human DNA oncogenic viruses and their transforming protein interactions with cell
      cycle control proteins.
AB  - PURPOSE: Both oncogenic viruses and cell cycle control proteins are fast-growth
      research areas. More and more evidence indicates that virus infection and
      replication are often associated with apoptosis and interfere with cell cycle
      pathways. To understand the mechanisms by which viral proteins regulate apoptosis
      and target the cellular pathways may lead to the development of new remedies for
      some cancers. DATA SOURCES: English literature searched by MEDLINE from January
      1995 to August 1998. STUDY SELECTION AND DATA EXTRACTION: More than one hundred
      research papers published in these areas over the past three years. Only new and
      important breakthroughs in these papers are selected. The review focuses on DNA
      viruses associated with the development of human cancers. RESULTS AND
      CONCLUSIONS: Some DNA viruses contain oncogenic proteins which transform normal
      cells in vitro and induce tumors in animals. These viral proteins target the
      cellular pathways and block apoptosis induced by receptors or in response to
      signal transduction. Viral interference with host cell apoptosis leads to
      enhanced viral replication and may promote carcinogenesis. Oncogenes and tumor
      suppressor genes, such as Retinoblastoma (RB) and p53, play important roles in
      regulation of these interactions.

PMID- 11593525
TI  - Medulloblastoma.
AB  - OBJECTIVE: To elucidate the diagnosis, treatment and prognosis of medulloblastoma
      in both children and adults. METHODS: A retrospective review was conducted in 80
      patients with medulloblastoma confirmed pathologically during the period of 1984
      and 1995. Multivariate analysis and comparison were made of the therapeutic
      effects of operation, radiotherapy and chemotherapy as well as the survival
      period. RESULTS: There were 42 males and 38 females with average age at diagnosis
      being 9.1 years in children and 25.1 years in adults. All patients were operated
      on to remove the tumour. Cerebral aqueduct re-opening was got through in 54 cases
      (67.5%), and Torkilsen's shunt was carried out at the same time for the rest
      patients. Seventeen patients had ventriculoperitoneal shunt, and 13 of them were
      performed after surgical excision of the tumour. Complete follow-up information
      was obtained in 61 patients (76%) for a period of 6 months to 14 years. During
      the follow-up, 27 patients received postoperative craniospinal irradiation, and
      27 local radiation. Fourteen patients were subjected to adjuvant chemotherapy.
      The overall 5-year and 10-year survival rates were 50.5% and 27.89% respectively.
      The 5-year survival rate was higher in adults than in children (P < 0.05),
      whereas the 10-year survival rate was similar. Thirty-two patients died of
      relapse or metastasis between 6 months and 10 years after initial surgical
      therapy, and the mean recurrence time was 3.5 years. CONCLUSIONS: Operation and
      postoperative regular radiotherapy were important therapeutic modalities for
      medulloblastoma. Total or subtotal removal of the tumour combined with
      craniospinal radiotherapy can improve patients' survival rate. The survival
      period of medulloblastoma patients is consistent with Collins' law, that is, the
      period of risk for survival is the age at initial diagnosis plus 9 months. Only
      few patients can gain long-term survival.

PMID- 11593526
TI  - Quality of life of patients with mild hypertension treated with captopril: a
      randomized double-blind placebo-controlled clinical trial.
AB  - OBJECTIVE: To determine the quality of life (QOL) of mild hypertensive patients
      treated with captopril as compared to placebo. METHODS: This is a randomized,
      double-blind, placebo-controlled clinical trial held in the out-patient clinic of
      Zhong Shan Hospital. Adult patients aged from 28 to 75 years with mild
      hypertension defined as diastolic blood pressure from 90 to 105 mm Hg were the
      inclusion criteria of the study. There were 278 patients who were eligible to
      enter the study. They were randomized to receive captopril or placebo 25 to 50 mg
      bid for 12 weeks. Change of QOL was compared both quantitatively and
      qualitatively between captopril and placebo groups. Change of blood pressure and
      side effects were also compared. RESULTS: With intention-to-treat analysis,
      significantly more improved QOL patients could be found qualitatively in patients
      with captopril treatment (45.3% vs 23.7%, P = 0.0002 for physical health domain;
      48.9% vs 26.6%, P = 0.0002 for mental health domain; 33.8% vs 11.5%, P = 0.0001
      for general function domain). Quantitatively, the change of score of mental
      health, general function and total QOL of captopril (3.18 +/- 5.90; 1.65 +/-
      4.43; 7.84 +/- 11.03) were significantly higher than those of placebo (1.32 +/-
      5.13, P = 0.00004; 0.64 +/- 3.45, P = 0.0008; 4.19 +/- 10.33, P = 0.0025
      respectively), and the change of score of physical health domain (3.01 +/- 5.26
      vs 2.23 +/- 4.79, P = 0.044) was of borderline statistical significant
      difference. Blood pressure was significantly lowered by captopril than by placebo
      (P = 0.000). CONCLUSION: Compared with the placebo, captopril is not only
      effective in lowering blood pressure, as has been established, but also effective
      in improving QOL in mild hypertensives.

PMID- 11593527
TI  - Effects of Curcuma Longa on proliferation of cultured bovine smooth muscle cells
      and on expression of low density lipoprotein receptor in cells.
AB  - OBJECTIVE: To investigate the inhibitory effects of aqueous turmeric extract
      (AqT) and serum of rats orally treated with ethanol extract of turmeric (SeT) on
      proliferation of vascular smooth muscle cells (VSMC) and its effects on the
      expression of low density lipoprotein receptor (LDL-R) antigen on the surface of
      smooth muscle cells. METHODS: Enzyme-linked immunosorbent assay (ELISA) for the
      expression of LDL-R protein and thiazolyl blue (MTT) assay for the proliferation
      of VSMC were used in this study. RESULTS: Both aqueous turmeric extract (AqT) and
      serum of rats orally treated with ethanol extract of turmeric (SeT) could inhibit
      10% serum activated proliferation of VSMC. The inhibition shown in both
      experiments was dose-dependent with an inhibitory rate of 18.9% at 20 mg/ml AqT
      and rate of 20.1% at 10% SeT respectively. AqT up-regulated the expression of LDL
      R protein with a highest rate at 5 mg/ml AqT in 3% lipoprotein deficient serum
      (LPDS). SeT did not show significant effect on the expression of LDL-R on the
      surface of VSMC. CONCLUSION: The extracts of turmeric may be extended to decrease
      the risk of atherosclerosis (AS).

PMID- 11593528
TI  - Electrophoresis of creatine kinase isoforms: a highly sensitive fluorescence
      scanning method.
AB  - OBJECTIVE: To develop an agarose electrophoretic method for creatine kinase (CK)
      isoforms, using highly sensitive fluorescence scanning. METHODS: A discontinuous
      buffer system was used. Electrophoresis on agarose gel was performed under
      constant current and low voltage. CK isoforms were separated within 30 minutes
      and detected by fluorescence scanning. RESULTS: There were no significant
      differences when the activities of CK-MM were between 853.0 U/L and 14.0 U/L and
      those of CK-MB between 152.0 U/L and 2.4 U/L. The detection limits of stain
      method for CK-MM and CK-MB isoforms were 36.0 U/L and 12.3 U/L, respectively;
      while those of fluorescence method were 12.0 U/L and 2.1 U/L. The experimental
      results showed good precision for CK-MM isoforms, as well for CK-MB isoforms and
      isoenzymes. CONCLUSION: An agarose electrophoretic method has been developed to
      measure CK isoenzymes and isoforms clinically. This method is rapid, simple,
      sensitive, highly reproducible and inexpensive. It is suitable for general
      laboratories.

PMID- 11593529
TI  - Study of activity of promoter from mouse alpha 2(I) procollagen gene.
AB  - OBJECTIVE: To clarify the segment and sequence in mouse alpha 2(I) procollagen
      gene which are responsible for high transcriptional activity during fibrogenesis.
      METHODS: This study was focused on further fractional analysis of 2 kb-length
      mouse alpha 2(I) procollagen gene promoter activity. Six chimeric genes were
      constructed in which various lengths of sequences between 2000 bp upstream of the
      start of transcription of the mouse alpha 2 (I) procollagen gene and 54 bp
      downstream of this site were fused to chloramphenicol acetyltransferase (CAT)
      reporter gene. These recombinant plasmids were transfected transiently to
      collagen-producing cells (NIH/3T3) and non-collagen-producing cells (COS7) with
      liposomal transfection method. The activities of putative promoters were observed
      and compared by means of CAT measurement in the transfected cells. RESULTS: The
      highest and partial cell specific CAT expression was observed in construction
      driven by -780 to  bp fragment. The construction containing sequence deleted the
      proximal 500 bp from the transcription start site and part of exon I, and
      resulted in the lowest CAT expression. CONCLUSIONS: Some essential elements might
      exist in the 500 bp fraction proximal to transcription start site and part of
      exon I in mouse alpha 2(I) procollagen gene. The high potential promoter sequence
      between -780 bp from the start of transcription site and  bp from this site is of
      great significance in our following study of searching for specific DNA-binding
      proteins in activated collagen-producing cells.

PMID- 11593530
TI  - The clinical and epidemiological significance of serum PreS1/anti-PreS1 in HBV
      infection.
AB  - OBJECTIVE: To investigate whether PreS1 antigen and/or anti-PreS1 antibody in
      serum might have some significance different from routine hepatitis B virus (HBV)
      markers in hepatitis B virus infection. METHODS: Forty-six acute hepatitis B
      patients and 377 chronic persistent hepatitis patients were examined to assess
      the clinical significance of serum PreS1/anti-PreS1. HBV family clustering
      analysis was carried out in a village in Shanghai suburb area, and case-control
      study on role of PreS1 in HBV spreading was undertaken in Tangshan, Hebei
      province. RESULTS: PreS1 in HBsAg positive sera from chronic persistent hepatitis
      patients correlated with HBV DNA (P < 0.05), while the presence of PreS2 in HBsAg
      positive sera was much more common than that of PreS1 and had no correlation with
      HBeAg or HBV DNA. Among 46 patients with acute hepatitis B, the appearance of
      anti-PreS1 antibody in serum correlated with the disappearing or decreasing of
      both PreS1 and ALT. In antiviral treatment, PreS1 antigen turned negative much
      earlier than PreS2 and HBsAg in acute hepatitis B patients' sera. Family
      clustering analysis suggested that people with PreS1 positive in serum were more
      infective than those with HBsAg positive alone (P < 0.01). The case-control study
      showed that chronic hepatitis B patients with PreS1 positive in serum played a
      much more important role in HBV spreading than those with PreS1 negative (P <
      0.01) and asymptomatic HBsAg carriers (P < 0.01), and the odds ratios (OR) were
      3.8 and 3.2, respectively. CONCLUSIONS: Serum PreS1 closely correlates with
      active virus replication, and PreS1/anti-PreS1 status indicates the outcome of
      acute hepatitis B. The serum PreS1/anti-PreS1 marker is of some significance in
      HBV epidemiology as well.

PMID- 11593531
TI  - Effects of Kupffer cells stimulated by triglyceride and very low-density
      lipoprotein on proliferation of rat hepatic stellate cells.
AB  - OBJECTIVE: To study the effects of triglyceride, very low-density lipoprotein
      (VLDL), and Kupffer cell-conditioned medium (KCCM) derived from triglyceride and
      VLDL treatment on proliferation of rat hepatic stellate cells (HSC). METHODS: HSC
      and Kupffer cells were isolated and cultured from liver of Wistar rats by in situ
      perfusion with proteinase and collagenase, and density gradient centrifugation
      with Nycodenz; HSC and Kupffer cells were identified by immunohistochemistry,
      endocytosis, and ultrastructure, etc. Kupffer cells were incubated with
      triglyceride (25 micrograms/ml) and VLDL (25 micrograms/ml) for 24 hours, KCCM
      were prepared, and MTT colorimetric assay was detected for HSC proliferation.
      RESULTS: HSC proliferation was 0.1894 +/- 0.0316 (12.5 micrograms/ml), 0.1637 +/-
      0.0243 (25 micrograms/ml), 0.1450 +/- 0.0264 (50 micrograms/ml), 0.1212 +/-
      0.0275 (100 micrograms/ml), 0.1226 +/- 0.0138 (200 micrograms/ml) and 0.0990 +/-
      0.0163 (400 micrograms/ml) in the presence of triglyceride and was 0.1583 +/-
      0.0314 (6.25 micrograms/ml), 0.1642 +/- 0.0269 (12.5 micrograms/ml), 0.1834 +/-
      0.0498 (25 micrograms/ml), 0.1964 +/- 0.0287 (50 micrograms/ml) and 0.2202 +/-
      0.0284 (100 micrograms/ml) in presence of VLDL, respectively. Compared with the
      control, HSC proliferation at 400 micrograms/ml of triglyceride was lower (P <
      0.01), but at 12.5 micrograms/ml of triglyceride and 25, 50, 100 micrograms/ml of
      VLDL higher (P < 0.05 or 0.01); HSC proliferation was 0.1569 +/- 0.0144, 0.1924
      +/- 0.0113 and 0.1871 +/- 0.0116 in the presence of KCCM, KCCM + triglyceride and
      KCCM + VLDL, respectively. Compared with the control and KCCM, KCCM +
      triglyceride and KCCM + VLDL might promote HSC proliferation (P < 0.01); there
      was no statistical significance between KCCM + triglyceride and KCCM + VLDL (P >
      0.05); KCCM was greater in HSC proliferation than the control, but there was no
      significant change (P > 0.05). CONCLUSIONS: Triglyceride, VLDL, and KCCM
      stimulated by triglyceride and VLDL might promote HSC proliferation and be
      associated with fatty liver and hepatic fibrogenesis.

PMID- 11593532
TI  - Expression of autotaxin mRNA in human hepatocellular carcinoma.
AB  - OBJECTIVE: To investigate the expression of autotaxin (ATX) mRNA existed in the
      human hepatocellular carcinoma (HCC), and whether there is relation between the
      level of ATX expression and clinicopathological features of HCC. METHODS: Five
      normal liver tissues and 32 histologically verified HCC specimens were obtained.
      Semi-quantitative reverse transcription polymerase chain reaction was used to
      detect mRNA expression of ATX. RESULTS: ATX was expressed in all 32 HCC and 5
      normal liver tissues. The mean expression level of ATX gene in HCC samples was
      higher than that in normal liver tissues (68.23% +/- 15.31% vs. 31.97% +/- 8.05%,
      P < 0.001). Patients were divided into two groups: low ATX HCC (15 cases) and
      high ATX HCC (17 cases) by the cutoff point of median value. Intrahepatic
      metastasis, vascular invasion and poor differentiation were more frequently noted
      in HCC patients with high ATX expression than in patients with low ATX
      expression. CONCLUSION: ATX gene was found to be overexpressed in some HCC and
      correlated with HCC development and metastases.

PMID- 11593533
TI  - Diagnosis of gastroesophageal reflux disease in elderly subjects using 24-hour
      esophageal pH monitoring.
AB  - OBJECTIVE: To evaluate the relationship between the parameters of 24-hour
      esophageal pH monitoring and gastroesophageal reflux disease (GERD) among elderly
      subjects. METHODS: Twenty-four-hour esophageal pH monitoring was carried out in
      20 elderly subjects without apparent GERD symptoms (controls) and 69 suspected
      GERD subjects. RESULTS: Normal values of the parameters from 20 elderly controls
      were obtained. Percent of total time, percent of supine time and percent of
      upright time in which the pH was < 4 (indicating reflux) were less than 3.3%,
      1.4%, 5.5%, respectively. The number of reflux episodes and episodes lasting
      longer than 5 minutes were less than 65 and 2 times respectively. The values
      obtained in 66 GERD suspected subjects were significantly different from those in
      normal controls. The differences of reflux parameters between the esophagitis
      group and non-esophagitis group, such as percent of total time with pH < 4,
      percent of supine time with pH < 4 and number of reflux lasting longer than 5
      minutes were also significant. CONCLUSIONS: About 51.6% patients (34/66) with
      reflux symptoms but without endoscopic evidence of esophagitis were definitely
      diagnosed as GERD by esophageal pH monitoring. Duration of esophageal acid
      exposure correlated with the severity of GERD.

PMID- 11593534
TI  - Schedule-dependent reversion of cisplatin resistance by 5-fluorouracil in a
      cisplatin-resistant human lung adenocarcinoma cell line A549DDP.
AB  - OBJECTIVE: To study the schedule-dependent reversion of cis
      diamminedichloroplatinum (CDDP) resistance by 5-fluorouracil (5-Fu) in a CDDP
      resistant human lung adenocarcinoma cell line A549DDP. METHODS: Dimethylthiazol
      dipheryltetrazolium bromide (MTT) assay and immunocytochemistry were used.
      RESULTS: After the A549DDP was treated with CDDP, followed immediately by
      exposure to 5-Fu, cytotoxicity of CDDP increased 1.8 fold. After pretreatment of
      A549DDP with 5-Fu, followed immediately by exposure to CDDP, the cytotoxicity of
      CDDP increased 3.9 fold. After pretreatment of A549DDP with 5-Fu, after a 24- or
      48-hour drug-free interval, followed by exposure to CDDP, the cytotoxicity of
      CDDP increased 20 and 250 fold, respectively, and the A549DDP was rendered more
      sensitive than its parental cell line A549. In parallel with the increased
      cytotoxicity, the cellular GSH content was significantly reduced at 24 or 48-hour
      after 5-Fu pretreatment. However, depletion of GSH by buthionine sulfoximine
      (BSO) only resulted in partial reversion of CDDP resistance. 5-Fu could also
      inhibit the expression of MRP, but had no effect on the expression of GST pi. The
      effect of 5-Fu on the parental cell line A549 was much smaller than that in
      A549DDP. CONCLUSION: Scheduled administration of 5-Fu can reverse CDDP resistance
      completely through reduction of GSH and inhibition of MRP expression.

PMID- 11593535
TI  - Effect of ionizing radiation on liver mitochondrial respiratory functions in
      mice.
AB  - OBJECTIVE: To investigate the radiation effect on mitochondria of the mouse liver
      in vivo. METHODS: Livers of BALB/c mice were squeezed out through openings cut on
      the upper abdomen and radiation doses were delivered only to the livers.
      Radiation effects on the structure and function of liver mitochondria were
      evaluated from both respiratory control ratio (RCR) and ADP/O (adenosine 5'
      diphosphate/oxygen) ratio supported by two substrates, succinate and
      glutamate/malate mixtures. RESULTS: The data showed that both state 3 and state 4
      respiratory rates were significantly decreased concomitantly with the increase of
      radiation dose up to 20 Gy. Succinate-supported, but not glutamate/malate
      supported, respiratory control ratio, was also decreased with the increase of
      radiation dose. ADP/O ratios measured from the support of both succinate and
      glutamate/malate were not changed by gamma-radiation. This differential radiation
      damage indicated that respiratory control ratio was more vulnerable to radiation
      than oxidative phosphorylation. CONCLUSIONS: Although the functional integrity of
      ATP synthetic machinery of the mitochondria was not perturbed by ionizing
      radiation under 20 Gy, the structural integrity of mitochondrial membrane might
      be affected by ionizing radiation at a dose-dependent manner.

PMID- 11593536
TI  - Experimental observation of effects of triclabendazole on Paragonimus westermani
      infection in dogs.
AB  - OBJECTIVE: To observe the therapeutic effects of triclabendazole in the treatment
      of dogs with Paragonimiasis westermani. METHODS: Six dogs were experimentally
      infected, each with 100 metacercariae of Paragonimus westermani intraperitoneally
      and divided into untreated and treated groups, 3 dogs were treated orally with
      triclabendazole 100 mg/kg.d-1 for 2 consecutive days on day 170 after infection.
      Stool egg count was done by Stoll method. All dogs were killed on day 38 after
      treatment and the number of worm cysts and worms in the lungs were examined by
      naked eye and microscopically. RESULTS: Stool eggs became negative from day 7 to
      day 14 after starting chemotherapy in treated dogs. The numbers of worm cysts in
      the lungs of untreated dogs were 18, 24 and 24 on necropsy, while those in the
      treated dogs were 10, 7 and 4, respectively. The numbers of adult worms in the
      untreated dogs were 38, 51 and 42, while in the treated dogs only 2 small adult
      worms were found in one dog and no worm was found in the other two dogs. The mean
      worm reduction rate was 98.5%. CONCLUSION: Triclabendazole is highly effective
      against Paragonimus westermani in experimentally infected dogs.

PMID- 11593537
TI  - A diagnostic kit to screen individuals with glucose-6-phosphate dehydrogenase
      defect and its application on anti-malaria spot in the countryside.
AB  - OBJECTIVE: To prepare a kit for screening individuals with glucose-6-phosphate
      dehydrogenase (G6PD) defect. The kit is easy to use and to get the fast as well
      as reliable results. Especially it is suitable for the anti-malaria spots usually
      located in the remote countryside where no electricity is available. METHODS: The
      double filter paper method and other 2 techniques, the quantitative method and
      the single filter paper method, were used to determine G6PD activity in 70
      samples of human erythrocytes. It was found that the results of the double filter
      paper method and those of the single filter paper method in the first 8 hours
      after the drying of the blood-soaked filter paper were consistent with those of
      the quantitative method. When a piece of blood-soaked paper is left under room
      temperature more than 24 hours, G6PD in the erythrocytes deteriorated
      spontaneously and consequently the number of positive cases increased along with
      the elapse of time. RESULTS: Satisfactory results were achieved when the kit was
      used to screen cases of G6PD defect from 151 farmers who were receiving anti
      malaria therapy. The kit was made according to a technique named "double filter
      paper" method. CONCLUSIONS: These findings suggest that the double filter paper
      method can reveal the level of G6PD activity and the results are rapidly obtained
      when the method is used on the anti-malaria spot.

PMID- 11593538
TI  - Combination of all-trans retinoic acid with butyric acid and its prodrugs
      markedly enhancing differentiation of human acute promyelocytic leukemia NB4
      cells.
AB  - OBJECTIVE: To use NB4, an authentic human acute promyelocytic leukemia cell line,
      as well as the marrow cells from patients with acute promyelocytic leukemia
      (APL), containing the PML/RAR alpha fusion gene and fused protein to examine the
      growth inhibition and cytodifferentiation induced by all-trans retinoic acid
      (ATRA), butyric acid (BA) and its prodrug tributyrin (TB) either as a single
      agent or in combinations. METHODS: NB4 and APL cells were cultured in presence of
      ATRA, BA and TB respectively either as a single agent or in combinations at
      various concentration ratio. Cell growth was measured and myeloid differentiation
      was determined by morphology and the percentage of positive nitroblue tetrazolium
      reduction (NBT) on consecutive days over the whole process of culture. RESULTS:
      NB4 cells can be induced by ATRA alone and synergistically induced by the
      combinations of BA or TB with ATRA to differentiate. The synergy was reflected by
      a remarkable decrease in the effective concentration of ATRA required in the
      combinations in comparison with it as a sole agent. The combinations also
      shortened the time for the cells to reach the same level of maturation as that
      needed for ATRA alone. The potentiation on ATRA-induced differentiation of NB4
      cells seemed depending on an appropriate concentration ratio of each inducer in
      the combinations and the time of action. A preliminary result of in vitro
      induction of primarily cultured leukemic cells from APL patients by the combined
      inducers was promising. CONCLUSION: The combinations of ATRA with BA or TB at an
      appropriate ratio may improve the clinical outcome of differentiation therapy for
      APL patients.

PMID- 11593539
TI  - P2Z purinoceptor, a special receptor for apoptosis induced by ATP in human
      leukemic lymphocytes.
AB  - OBJECTIVE: To investigate the role of purinergic P2Z receptors for apoptosis of
      human leukemic lymphocytes mediated by extracellular adenosine triphosphate
      (ATP). METHODS: A total of 13 B-chronic lymphocytic leukemia (CLL) patients were
      studied. Exposure of leukemic lymphocytes with (n = 8) or without (n = 5) P2Z
      receptors to ATP, benzoylbenzoic-ATP (BzATP), 2-methylthio-ATP (2MeSATP),
      adenosine-5' [gamma-thio] triphosphate (ATP-gamma S), and other nucleosides for 8
      h in vitro. Apoptosis was detected by electron microscopy (EM), agarose gel
      electrophoresis, and the quantitative assay-TdT assay. RESULTS: Apoptosis was
      detected only in leukemic lymphocytes with P2Z receptors. Using a quantitative
      assay, ATP-induced DNA strand breaks were found to occur specifically with BzATP,
      ATP and 2MeSATP, but not for analogue ATP-gamma S nor other nucleosides.
      Meanwhile, ATP-induced DNA fragmentation was fully blocked by pretreatment with
      oxidized ATP (OxATP), a compound recently shown to block P2Z receptors. Also, it
      is shown that the Ca2+/calmodulin complex plays a role in the regulation of the
      apoptosis induced by ATP on CLL cells, because an antagonist of this complex, 1
      [N, O-bis (5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62)
      was found to inhibit the ATP-induced apoptosis. Furthermore, choline, an
      inhibitor of phospholipase D (PLD), is first shown to partially inhibit ATP
      induced apoptosis. CONCLUSION: These data indicate that P2Z receptors on
      lymphocytes play an important role in the apoptosis induced by ATP in vitro.

PMID- 11593541
TI  - Intercellular adhesion molecule-1 and accumulation of eosinophils in nasal polyp
      tissue.
AB  - OBJECTIVE: To investigate the relationship between intercellular adhesion
      molecule-1 (ICAM-1) and the accumulation of eosinophils in nasal polyp tissue to
      better understand the mechanism of airway eosinophilic inflammation. METHODS: The
      expression of ICAM-1 and its natural ligand, lymphocyte function-associated
      antigen-1 (LFA-1), in normal nasal mucosa from 6 controls and in nasal polyp
      tissue from 19 patients with nasal polyposis were determined with
      immunohistochemistry. With dual immunohistochemistry and May-Griunwald Giemsa
      stain (MGG), the expression of LFA-1 and infiltrating eosinophils in nasal polyp
      tissue was observed. RESULTS: The expression of ICAM-1 and LFA-1 was stronger in
      the nasal polyp tissue than in normal nasal mucosa. There was a positive
      relationship between the infiltration of eosinophils and the expression of LFA-1
      on eosinophils. CONCLUSION: Accumulation of eosinophils in nasal polyp tissue is
      associated with the counter-effect between adhesion molecules and its ligand on
      eosinophils.

PMID- 11593540
TI  - Interrelation between nitric oxide and endothelin-1 in an experimental acute
      hypoxia in rats and its intervention.
AB  - OBJECTIVES: To study the interrelation between nitric oxide (NO) and endothelin-1
      (ET1) in experimental acute hypoxic rats, and to evaluate the mechanism of acute
      hypoxic pulmonary hypertension affected by NO and ET1 and its intervention.
      METHODS: Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase
      histochemical staining method, Griess biochemical assay and radioimmune assay
      were applied to investigate the changes of nitric oxide syntheses (NOS), NO and
      ET1 in normal, hypoxic, and L-Arginine (L-Arg) and dexamethasone treated hypoxic
      rats. RESULTS: In normal rats, the NOS stain was localized in pulmonary vascular
      endothelium, and in the hypoxic rats, the activity of NOS was significantly
      lower. The level of plasma NO was significantly lower during acute hypoxia, but L
      Arg as well as dexamethasone could prevent the drop of plasma NO. The level of
      plasma ET1 rose up significantly in the acute hypoxic rats, but after L-Arg
      therapy, it was significantly reduced, however, dexamethasone could not affect
      plasma ET1. The level of plasma cyclic guanosine monophosphate (cGMP) was
      significantly lower in the acute hypoxic rats, and L-Arg could prevent the drop
      of plasma cGMP, but dexamethasone could not prevent the drop of plasma cGMP.
      CONCLUSIONS: NO and ET1 may modulate hypoxic pulmonary hypertension and acute
      hypoxia can result in acute hypoxic pulmonary hypertension. L-Arg can reverse the
      acute hypoxic pulmonary hypertension. Further study is needed if dexamethasone is
      beneficial in acute hypoxic diseases. NO may play an important role in physiology
      of the lung and acute hypoxic diseases.

PMID- 11593542
TI  - Effect of donor antigen-trichosnthin conjugate in induction of mouse to rat
      cardiac xenografting tolerance.
AB  - OBJECTIVE: To investigate the special effect of donor antigen-trichosnthin (TCS)
      conjugate on depleting the immune reactive cells that respond to xenograft, and
      thus inducing specific xenograft tolerance. METHODS: Rat anti-mouse antibodies
      coupled sepharose-4B beads were used to purify mouse H-2 antigens by affinity
      chromatography. Those purified H-2 antigens were conjugated with TCS by
      heterobifunctional reagents SPDP [3-(2-pyridyldithio) propionic acid
      hydroxysuccinimide ester] and 2-IT (2-iminothiolane). The specific inhibition
      function of Ag-TCS to recipient's immune cells was measured in vitro. Ag-TCS
      conjugate (200 micrograms/kg, i.v.) was administered to the recipients (rats) 4
      days prior to cardiac xenotransplantation of mouse to rat. RESULTS: In vitro, the
      proliferation of immune reactive cells in the recipients pretreated with Ag-TCS
      was inhibited. The Ag-TCS conjugate significantly prolonged the cardiac survival
      time (6.88 +/- 1.36 days) compared with cyclosporine A (CsA) group (2.83 +/- 0.75
      days) (P < 0.01). CONCLUSION: Donor Ag-TCS conjugate can induce specific
      tolerance to xenograft.

PMID- 11593543
TI  - Proliferative activity in cervical intraepithelial neoplasia and cervical
      carcinoma.
AB  - OBJECTIVE: To detect the proliferative activity of cervical cells in cervical
      intraepithelial neoplasia (CIN) and cervical carcinoma by using proliferating
      cell nuclear antigen (PCNA) immunohistochemistry and mitotic index (MI). METHODS:
      Sixty specimens of CIN and cervical carcinoma from patients treated at the
      Obstetrics and Gynaecology Hospital, Shanghai Medical University, were analyzed.
      Among them, 8 were CIN I-II, 16 CIN III, 18 squamous carcinoma, and 18
      adenocarcinoma. Serial 4 microns sections were prepared for haematoxylin and
      eosin (HE) staining to observe mitotic figure and pathological grading and for
      immunohistochemical staining of PACN which was performed by murine monoclonal
      antibody PC 10 (DAKO-PCNA). RESULTS: PCNA index (PI) and MI of CIN III and
      cervical carcinoma were significantly higher than those of normal cervix and CIN
      I-II. PI and MI increased with progress of disease. In addition, higher level of
      PI was correlated with higher level of MI, and higher levels of PI and MI were
      related with higher histological grade. However, there was no significant
      relationship between PI, MI, clinical staging, and lymph node metastases.
      CONCLUSION: PCNA and mitotic figure are useful for evaluating proliferative
      activity in CIN and cervical carcinoma, and could be used to distinguish CIN III
      from CIN I-II and evaluate the malignant potential of tumour tissues.

PMID- 11593544
TI  - Mifepristone in treating ectopic pregnancy.
AB  - OBJECTIVE: To explore the effect of mifepristone in treating ectopic pregnancy.
      METHODS: Thirty-eight patients with ectopic pregnancy and without tubal rupture
      or tubal abortion, aged between 23 and 46 years, were studied. The stage of
      amenorrhoea ranged from 34 to 51 days. The patients took mifepristone at a dosage
      2 times anti-early pregnancy dosage. The symptoms, and serum human chorionic
      gonadotropin (beta-hCG) levels were monitored, and ultrasonic examination
      performed at regular intervals. RESULTS: Thirty-seven of 38 patients were cured,
      the success rate being 97.4%. CONCLUSION: Mifepristone is safe and effective to
      treat ectopic pregnancy.

PMID- 11593545
TI  - Assessment of serial changes of bone mineral density at lumbar spine and femoral
      neck before and after liver transplantation.
AB  - OBJECTIVE: To assess serial changes of bone mass before and after orthotopic
      liver transplantation (OLT). METHODS: Consecutive bone mineral density (BMD) of
      lumbar spine (L2-L4) and femoral neck in 38 patients with chronic liver failure
      within 2 months before OLT, 6, 12 and 24 months after OLT was determined using
      dual energy X-ray absorptiometry. RESULTS: 29% of 38 patients before OLT had
      osteoporosis (BMD below 2 standard deviate). BMD levels at L2-L4 and femoral neck
      decreased and incidence of osteoporosis increased in the first 6 months after
      OLT. Over beyond 6 months post-OLT BMD levels at L2-L4 increased to just slightly
      above the pretransplant level and incidence of osteoporosis decreased from 36.8%
      (6 months after OLT) to 7.9% (24 months after OLT). Although BMD levels at
      femoral neck by 12 and 24 months after OLT gradually increased, BMD levels at
      femoral neck were still lower than those before OLT. CONCLUSIONS: There was
      already a low bone mass in patients with chronic liver disease before OLT and
      liver transplantation induced a marked and rapid bone loss.

PMID- 11593546
TI  - MRI imaging appearance of lumbosacral agenesis.

PMID- 11593547
TI  - Growth hormone deficiency in adults and clinical use of recombinant human growth
      hormone.
AB  - OBJECTIVE: To review the modern recognition of growth hormone deficiency (GHD) in
      adults and the beneficial effects of growth hormone (GH) treatment in such cases.
      DATA SOURCES AND METHODS: Most published original articles about GH and GHD in
      recent domestic and world wide related literatures were available. STUDY
      SELECTION: More than 65 originally identified articles were reviewed and 29 were
      selected that especially addressed the stated purpose. RESULTS: Treatment of GHD
      in adult human beings became an option following the development of rhGH and the
      numerous reports on the effect of rhGH therapy in such patients. The syndrome of
      GH deficiency in adults principally comprises abnormalities in body composition,
      cardiovascular risk factor, and psychological well-being. In comparison with
      normal individuals, these patients have increased total-body fat mass
      (particularly visceral adiposity), reduced muscle mass, reduced muscle strength
      exercise performance, and reduced bone mass. The psychological dysfunction
      comprises self-reported reduction in energy, mood, and sleep, along with
      objective reductions in marital and socioeconomic performance. CONCLUSION: The
      evidence that rhGH administration may be beneficial for the prevention, as well
      as treatment, of various clinical situations.

PMID- 11593548
TI  - Immunological studies on the cellular phenotype involved in corneal allograft
      rejection.
AB  - OBJECTIVE: To investigate the cellular phenotype involved in corneal allograft
      rejection using wholemounts analysis. METHODS: Corneal transplantation was
      performed between Sprague Dawley (SD) and Wistar rats. Corneal wholemounts were
      prepared from control rats and those after corneal transplantation on day 7 and
      12. Immunohistochemical stain was performed on these wholemounts using monoclonal
      antibodies to transforming growth factor beta 1(TGF-beta 1), CD3, CD4, CD8, B
      lymphocytes, macrophages, dendritic cells and major histocompatibility complex
      (MHC) class II antigen. RESULTS: Corneal allograft rejection started on day 7 and
      reached its maximum from 10 to 14 days after corneal transplantation. Presence of
      TGF-beta 1-, CD3-, CD4-, CD8-, MHC class II-positive cells, macrophages and
      dendritic cells were noted at the limbus of both SD rats and Wistar rats. No
      positive cell was present in the central cornea of normal rats. All positive
      cells but B lymphocyte were noted in large numbers in the cornea after corneal
      allograft transplantation. Marked staining for TGF-beta 1 was noted during graft
      rejection. CONCLUSION: The corneal wholemounts technique provides a good
      visualization for the cellular phenotype involved in corneal allograft rejection.
      A variety of cells including TGF-beta 1, CD3, CD4, CD8, MHC class II antigen
      positive cells, macrophages and dendritic cells are involved in corneal allograft
      rejection. TGF-beta 1-positive cell might be an important immunosuppressive
      factor after corneal transplantation and also involved in the induction of
      fibrosis.

PMID- 11593549
TI  - Experimental study of growth of trabecular cells on the filters and hydraulic
      conductivity.
AB  - OBJECTIVES: To search the method of culturing human trabecular cells (HTC) on a
      filter support so as to provide a model to study the hydraulic conductivity of
      HTC in vivo. METHODS: The third passage of HTC was cultured on a nylon filter;
      after that we measured the rate of different irrigations through the filter with
      HTC [Lp, microliter/(min.mm Hg.cm2)]. RESULTS: HTC could continuously grow on the
      filters. The normal Lp was 10.45 microliters/(min.mm Hg.cm2). Irrigated by the
      solution of epinephrine (EPI) or dexamethasone (DEX), Lp of HTC were higher than
      that in controls of the same cultural time, while after being exposed to DEX for
      a few days, Lp was significantly decreased. CONCLUSIONS: (1) More information of
      hydraulic conductivity and effects of pharmacologic agents on HTC could be got
      from the dynamic filtery model; (2) EPI could improve the conductivity of HTC
      while DEX could have the same effect in early period.

PMID- 11593550
TI  - Treatment of early giant retinal tears with domestic perfluorodecalin and
      perfluoropropane.
AB  - OBJECTIVE: To explore the methods of lens-sparing (without lensectomy), non
      silicone oil tamponade and no scleral buckling for treatment of early giant
      retinal tears. METHODS: Thirteen cases of early retinal detachment of
      proliferative vitreoretinopathy (PVR) grade C2-D1, with giant tear extending from
      135 degrees to 270 degrees were chosen. Transscleral cryotherapy was first
      applied to treat each end of the giant tear up to the oral serrate. And then
      conventional three-port pars plana vitrectomy was performed. Perfluorodecalin
      liquid was injected to manipulate the flap of the retinal tear. The flap with no
      cryotherapy before was treated with endolaser or cryotherapy under optimal visual
      condition, then air-fluid was exchanged completely and C3F8 was injected
      properly. RESULTS: With a mean follow-up of 8.2 months, the retina was reattached
      completely in 12 eyes. Success rate was 92.3%, and visual acuity improved. Most
      postoperative complications were slight. The retina failed to reattach only in 1
      case with severe vitreous blood. CONCLUSIONS: In treating early retinal giant
      tears without severe PVR, the lens-sparing, non-silicone oil tamponade and no
      scleral bucking are helpful to simplify operation and to improve the success rate
      of the retinal surgery and to yield satisfactory outcome of visual acuity.
      Besides, it can also avoid the initial side effects of silicone oil tamponade and
      diopter irregularity after lensectomy.

PMID- 11593551
TI  - Corneal topographic analysis after excimer photorefractive keratectomy.
AB  - OBJECTIVE: To evaluate the corneal surface changes and visual quality after
      excimer photorefractive keratectomy (PRK) for myopia. METHODS: Corneal
      topographic analysis was performed on 23 patients (38 eyes) with myopia after PRK
      at the 1-, 3-, 6- month postoperative follow-up visits. RESULTS: The corneal
      sphericity was changed after excimer PRK. As time went on, the mean surface
      regularity index (SRI) and the surface asymmetry index (SAI) decreased gradually,
      and the corneal surface became more smooth; mean simulated keratoscope readings
      (SimK) showed a gradual restoration. At the 6-month postoperative examination,
      corneal topography showed four main patterns of ablation: round or oblong (50%),
      collar-button (23.68%), semicircular (18.42%) and central island (7.9%). Patterns
      of ablation were correlated with visual acuity. CONCLUSION: The quantitative
      analysis of corneal topography is essential for evaluating corneal surface
      changes after PRK and helpful in the surgical design of PRK and in predicting the
      refractive outcome with greater precision.

PMID- 11593552
TI  - Ultrasound biomicroscopic study on changes of ocular anterior segment structure
      after topical application of cycloplegia.
AB  - OBJECTIVES: To observe the changes of the ocular anterior segment structure and
      the relationship between the intraocular pressure (IOP) and these changes after
      the topical application of cycloplegia using ultrasound biomicroscope (UBM),
      especially to observe the changes of ciliary body thickness, ciliary process
      thickness and ciliary process-lens distance. METHODS: The quantitative
      measurement with UBM and the measurement of IOP were performed before and after
      the topical application of 2% homatropine solution in 48 normal eyes. The results
      were statistically analyzed. RESULTS: In the parameters showing the changes of
      the anterior chamber angle after topical use of 2% homatropine solution, both the
      trabecular iris angle and the angle opening distance 250 decreased. The iris
      thickness 1 increased. The anterior chamber became deeper and the iris-lens
      contact distance became shorter. All these differences were statistically
      significant (P < 0.05). In the parameters showing the changes of ciliary body,
      the ciliary body thickness and the ciliary process thickness decreased. The
      scleral ciliary body angle increased. The iris-zonule distance decreased and the
      ciliary process-lens distance increased. All these differences were statistically
      significant (P < 0.05). The IOP increased from 17.63 +/- 3.45 mm Hg to 18.23 +/-
      3.53 mm Hg after topical use of 2% homatropine solution, but the difference was
      not statistically significant (P > 0.05). CONCLUSIONS: After the topical use of
      cycloplegia, the anterior chamber becomes deeper. The anterior chamber angle
      becomes narrower, and the ciliary body becomes thinner and moves backward and the
      ciliary process-lens distance increases. By using UBM the structures of the
      ocular anterior segment in the living state can be observed and measured
      quantitatively. The ultrasound biomicroscopic imaging has its advantages in the
      morphological study of the ocular anterior segment.

PMID- 11593553
TI  - Structure and function of alleles in the 3' end region of human apoB gene.
AB  - OBJECTIVE: To study the structure of alleles in the 3' end of the apoB gene in
      Han, Mongolian and Tibetan populations in China as well as the roles in the
      regulation of gene expression. METHODS: DNA were obtained from human leukocytes
      by phenol-chloroform extraction and ethanol precipitation. PCR were carried out
      in a 50 microliters volume containing 50 ng genomic DNA as template. The Ssp1
      digested products were loaded on a gradient acrylamide gel and run for 3 hours.
      The constructs containing alleles were tested in cultured HepG2 and HeLa cells
      using transient assays. RESULTS: Sixteen alleles with different repeat number
      were characterized. All of the alleles varying from HVE22 to HVE52, allele HVE34
      was the most common (58.4%), followed by allele HVE36 (13.8%) and HVE32 (10.5%).
      258 PCR products were digested with Ssp1 and run in 4-12% PAGE. We detected the
      fragments of 266bp, 91 bp, 61 bp and 39 bp in almost all samples. The small
      alleles (including HVE22, HVE24, HVE26 and HVE36) decreased the expressive
      activity of the luciferase reporter, in contrary, the large alleles (including
      HVE44, HVE46 and HVE48) elevated obviously the expressive activity of the
      luciferase reporter. CONCLUSIONS: More alleles with different number of tandem
      repeats in 3' end of apoB gene exist in the Chinese populations. The alleles in
      3' end minisatellite of human apoB gene could control the expression of the gene
      itself.

PMID- 11593554
TI  - Association of polymorphism of apolipoprotein E gene with coronary heart disease
      in Han Chinese.
AB  - OBJECTIVE: To investigate the association between apolipoprotein E (apoE) gene
      polymorphism and coronary heart disease(CHD) in Han Chinese. METHODS: Apo E
      genotype was examined with the methods of hot start polymerase chain reaction
      (PCR) and restriction isotyping in samples of 113 unrelated Chinese healthy
      individuals and 93 patients with CHD. The relation of the gene polymorphism of
      apoE and levels of serum lipids, lipoproteins, and apolipoproteins was also
      studied. RESULTS: The results showed that the epsilon 4/3 genotype was more
      frequent in CHD cases than in control subjects (31.2% vs. 11.5%, P < 0.01). The
      frequency of the epsilon 4 allele in CHD cases was significantly higher than in
      control subjects (17.2% vs 7.5%, P < 0.01). The epsilon 4 allele was associated
      with high concentrations of serum TC (r = 0.265, P < 0.05), LDL-C (r = 0.266, P <
      0.05), and apoB (r = 0.360, P < 0.01). CONCLUSIONS: Hot start PCR assay is
      considered a rapid and simple technique for apoE genotyping. This method is
      suitable for routine laboratories and large scale population studies. Genetic
      polymorphism of the apoE gene might contribute to the determination of serum
      lipid profile and the development of CHD among Han Chinese.

PMID- 11593555
TI  - Enhancing effects of silkworm expressed recombinant human macrophage colony
      stimulating factor on hematopoietic recovery of irradiation-injured mice.
AB  - OBJECTIVE: To study the hematopoietic enhancing effects of recombinant human
      macrophage colony-stimulating factor (rhM-CSF) expressed in silkworm. METHOD:
      Balb/c mice were irradiated with sublethal dose of 60 Co gamma-rays and then
      administered intraperitoneally with silkworm expressed rhM-CSF (1000 U per
      individual for 7 days) in treatment group or with normal saline (for 7 days as
      well) in control group. The hematopoietic recovery of irradiation mice was
      observed by comparing peripheral white blood cell (WBC) counts, differential
      counts of WBC and bone marrow hematopoietic progenitor cell colony forming assay
      in soft agar at different time after irradiation. RESULTS: The total WBC counts
      (x 10(9)/L) of treatment group at day 15 and 20 after irradiation(3.42 +/- 1.20,
      5.56 +/- 2.50, respectively) were significantly higher than those of control
      group (2.03 +/- 0.90, 3.72 +/- 2.30; both P < 0.05). On days 10, 15, 20, 25 and
      30 after irradiation, the monocyte counts (x 10(9)/L) of treatment group (0.08 +/
      0.06, 0.16 +/- 0.10, 0.48 +/- 0.35, 0.47 +/- 0.21 and 0.33 +/- 0.17,
      respectively) were all significantly higher than those of control group (0.025 +/
      0.016, 0.05 +/- 0.04, 0.23 +/- 0.16, 0.33 +/- 0.19 and 0.17 +/- 0.13; all P <
      0.05). On days 15, 20 and 25, the granulocyte count (X 10(9)/L) of treatment
      group (1.03 +/- 0.61, 2.18 +/- 1.19 and 3.28 +/- 1.09) were also higher than
      those of control group (0.62 +/- 0.37, 1.40 +/- 0.99 and 2.20 +/- 0.74; all P <
      0.05). On day 9 after irradiation, the bone marrow CFU-GM yield of control group
      (19 +/- 11/10(6) cells) was significantly lower than that of treatment group (78
      +/- 30/10(6) cells, P < 0.05). CONCLUSION: rhM-CSF expressed in silkworm could
      accelerate hematopoietic recovery in irradiated mice.

PMID- 11593556
TI  - Preliminary study on application of artificial neural network to the diagnosis of
      Alzheimer's disease with magnetic resonance imaging.
AB  - OBJECTIVE: Artificial neural network is first used in the measurement study of
      brain of Alzheimer's disease using MRI, and a completely new pattern
      discriminating method is adopted, so as to take advantage of MRI to diagnose and
      identify AD patients. METHODS: 12 patients with probable AD (aged 65.33 +/- 8.62
      years) and 36 normal controls matched with age and gender (aged 65.81 +/- 74.37
      years) were studied. MRI are performed on Siemens Magnetom IMPACT 1.0 T; eight
      interesting brain structures including sixteen regions (left and right) indices
      are measured and studied; SPSS software and BP network software made by authors
      respectively were used to process and analyze the measured data. RESULTS: Using
      artificial neural network to the same regions and data, both the sensitivity and
      accuracy were found higher than using the traditional discrimination function
      analysis method; the indices of amygdala, hippocampus, parahippocampal gyrus,
      temporal lobe, and temporal horn, these five structures could completely
      differentiate AD from normal controls; new cases were successfully diagnosed.
      CONCLUSIONS: Artificial neural network combining with MRI is probable to become a
      useful and reliable clinical tool to diagnose AD patients.

PMID- 11593557
TI  - Cerebral amyloid angiopathy with dementia: clinicopathological studies of 17
      cases.
AB  - OBJECTIVES: To study clinicopathologically 17 cases of cerebral amyloid
      angiopathy (CAA) with dementia and to investigate the possible neuropathology of
      this disorder. METHODS: Of 362 autopsy cases, 17 who had had dementia with proved
      CAA were studied. Hematoxylin and eosin, Congo red, Bodian and beta/A4 protein
      immunohistochemical stain were used. Brain sections were observed under light
      microscopy and polarized light microscopy. The amyloid was confirmed by positive
      Congo red stain with apple-green birefringence under polarized light and positive
      beta/A4 immunohistochemical stain. The severity of amyloid deposit was graded as
      slight, moderate and severe. RESULTS: In the 17 cases of CAA associated with
      dementia, Alzheimer's disease was found in 3 cases, Pick's disease in 1, multi
      infarct dementia in 6, multi-hemorrhage dementia in 4, and pure CAA in 3.
      CONCLUSIONS: CAA not only is closely related to Alzheimer's disease, but also
      causes cortical multiple small infarcts and hemorrhagic lesions, which lead to
      dementia. Moreover, pure CAA may produce dementia through hypoperfusion of the
      cortex by CAA-related hyalinization and stenosis of the arteries, which lead to
      the loss of cortical neurons.

PMID- 11593558
TI  - Gene deletion and carrier detection in the family of Becker muscular dystrophy by
      short tandem repeat sequence polymorphism.
AB  - OBJECTIVE: To type haplotypes among the patients, carriers and normal offspring
      in a family of males with Becker muscular dystrophy in one generation by allelic
      fragment length polymorphism analysis. METHODS: Deletion analysis of the patients
      were performed using multiplex polymerase chain reaction (PCR) of amplification
      with 9 dystrophin exon primers. Intragenic short tandem repeat (STR) sequence
      (STR44, STR45, STR49 and STR50) were amplified by PCR to analyse allelic fragment
      length polymorphisms in the members of the family. RESULTS: The deletions of
      exons 17, 19 and 45, as well as deletions of allelic fragments at the loci of
      STR44 and STR45 were determined in the patients. Hemizygosity at those two loci
      were detected and carrier status ascertained in the mother of the patients. The
      normal haplotypes were typed in the sister of the patients. CONCLUSION: The
      method of STR sequence polymorphism analysis can determine haplotypes at normal
      status or at risk status. It would be used in prenatal diagnosis and carrier
      detection in the families of Duchenne and Becker muscular dystrophy.

PMID- 11593559
TI  - Normalization of auditory evoked potential and visual evoked potential in
      patients with idiot savant.
AB  - OBJECTIVE: To investigate the variations of auditory evoked potentials (AEP) and
      visual evoked potentials (VEP) of patients with idiot savant (IS) syndrome.
      METHODS: Both AEP and VEP were recorded from 7 patients with IS syndrome, 21
      mentally retarded (MR) children without the syndrome and 21 normally age-matched
      controls, using a Dantec concerto SEEG-16 BEAM instrument. RESULTS: Both AEP and
      VEP of MR group showed significantly longer latencies (P1 and P2 latencies of
      AEP, P < 0.01; N1 and N2 latencies of VEP, P < 0.01/0.05), lower P2 amplitudes (P
      < 0.01) and higher P3 amplitudes (P < 0.01), as compared with normal controls.
      But none of above-mentioned changes was found with IS group. Almost all MR
      patients (90.1%) presented P4 component in both AEP and VEP, which was also in
      sharp contrast with its incidence in other 2 groups (IS: 14.3%; normal controls:
      9.5%). CONCLUSION: Patients with idiot savant syndrome presented normalized AEP
      and VEP.

PMID- 11593560
TI  - Enzyme-linked immunoelectrotransfer blotting analysis of human serologic
      responses to infective hookworm larval antigen.
AB  - OBJECTIVE: To explore the possibility of using specific antigens for
      immunodiagnosis of hookworm disease in endemic area. METHOD: Infective third
      stage larvae of the canine hookworm, Ancylostoma caninum (A. caninum), were
      prepared as the source of antigen. Enzyme-linked immunoelectrotransfer blotting
      (EITB) was employed as an immunodiagnostic method. RESULTS: Two immunodominant
      bands of hookworm antigens (42 kDa and 55 kDa) were recognized by the sera of
      hookworm-infected patients (serum dilution 1:200; antigen centrifuged at 36,000
      r/m for 20 minutes, but not by sera from negative controls. CONCLUSION: The 42
      kDa and 55 kDa A. caninum antigens might be the specific antigens that could be
      used for immunodiagnosis of hookworm disease in endemic area.

PMID- 11593561
TI  - Aberrant expression of growth factor Wnt-5A in six urinary malignant cell lines.
AB  - OBJECTIVE: To investigate the expression of growth factor Wnt-5A in urinary tumor
      cell lines. METHODS: By semi-quantitative RT-PCR (reverse transcriptase
      polymerase chain reaction), the expression of Wnt-5A in six urinary malignant
      cell lines, one primary cultured renal fibroblast and one case of normal human
      renal tissue was detected using Gel Doc 1000 computer controlled molecular
      analysis system. RESULTS: The expression of Wnt-5A in-urinary tumor cell lines
      was much higher than that in primary cultured renal fibroblasts (PRF) and normal
      human renal tissue (NRT). The levels of Wnt-5A mRNA were different between six
      malignant cell lines. CONCLUSION: The overexpression of growth factor Wnt-5A has
      a potential effect on the oncogenesis of urinary malignancies.

PMID- 11593562
TI  - Important role of cardiac spect imaging in patients undergoing percutaneous
      transluminal coronary angioplasty.
AB  - OBJECTIVE: To examine the utilization and contribution of cardiac perfusion scans
      to patients undergoing percutaneous transluminal coronary angioplasty. METHODS:
      From July 1996 to January 1998, 34 patients underwent percutaneous transluminal
      coronary angioplasty and cardiac SPECT imaging was studied. Twenty-five patients
      had pre-procedure SPECT scans. The agreement between angioplasty strategies and
      SPECT findings of ischemia and hypokinesia was examined. RESULTS: When
      radionuclide imaging was performed before revascularization procedures, 84% of
      the patients had intervention strategies guided by scan findings. Perfusion scan
      findings including extent and severity of ischemia, degree of hypokinesia
      directed the selection of target vessel for angioplasty in the patient subgroup
      with multi-vessel disease. Post-angioplasty radionuclide cardiac scans were
      performed only on symptomatic patients, demonstrating ischemia and hypokinesia in
      most of them, conceivably reflected the selection bias. CONCLUSION: We recommend
      routine pre- and post-angioplasty radionuclide imaging with multigated scans for
      wall motion assessment for all patients receiving coronary intervention.

PMID- 11593563
TI  - Early detection of persistent trophoblastic tumour by serum human chorionic
      gonadotrophin monitoring after molar pregnancy.
AB  - OBJECTIVE: To study the outcome of a multi-centred post-molar pregnancy serum
      human chorionic gonadotrophin (hCG) surveillance programme. METHODS: Patients
      recruited into the multi-centred post-molar serum hCG surveillance programme
      between 1988 and 1996 were studied. The clinical data were obtained from medical
      records and computer database. RESULTS: There were 616 patients in the study.
      Twenty-five (11%) of 224 patients with molar pregnancy and 28 (7%) of 392
      patients with partial molar pregnancy were diagnosed to have persistent
      trophoblastic tumour (PTT) requiring chemotherapy. Of the 53 patients treated for
      PTT, 58.5% received intravenous methotrexate (MTX), 22.6% received both MTX and
      actinomycin D, and 19% received CHAMOC, a multiple chemotherapeutic regimen. Four
      patients receiving single drug had to change the regimen because of poor
      response, and all recovered and remained well. There were 3 cases of recurrence,
      one in each group of patients receiving single, dual or multiple agents. One
      patient died because of treatment complication. The rest were well with a mean
      follow-up of 42 months. CONCLUSIONS: Post-molar serum hCG surveillance is
      important to detecting persistent trophoblastic activity. Early treatment of PTT
      by the appropriate chemotherapy has a near hundred percent cure and prevents the
      progression of PTT into more advanced trophoblastic malignancy such as
      choriocarcinoma.

PMID- 11593564
TI  - Therapeutic efficacy of transcatheter arterial embolization of primary
      hepatocellular carcinoma: discrepancy in different histopathologic subtypes.
AB  - OBJECTIVE: To evaluate preliminarily the therapeutic efficacy of transcatheter
      arterial embolization (TAE) for different histopathologic subtypes of primary
      hepatocellular carcinoma (HCC). METHODS: A retrospective study of 226 patients
      with histopathologically diagnosed primary HCC was performed. The patients were
      treated with either single TAE, surgical resection of tumor alone, or TAE
      combined with surgical resection. Follow-up information was achieved in 157 of
      226 patients. Comparative analyses of survival data and image findings were
      performed with correlation to histopathologic classification and different
      therapeutic methods, respectively. RESULTS: Eight histopathologic subtypes of
      primary HCC were found in this group, including HCC of trabecular pattern,
      pseudoglandular pattern, fibrolamellar HCC and sclerosing HCC, as well as HCC of
      clear cell, of small cell, poorly differentiated or undifferentiated HCC, and
      hormonally active HCC. The accumulated survival rate for these 157 patients was
      74.52% of 1 year, 53.50% of 2 years, 31.85% and 14.01% of 3 and 5 years,
      respectively. Fibrolamellar HCC and clear cell HCC had relatively higher survival
      rate (25.00% and 33.22% of 5 years, respectively) than that of other subtypes,
      and the median survival time of the latter was 71 months. The mean survival time
      was 25.06 months (SE = 1.87) in single TAE group, 30.38 (SE = 2.05) months in
      surgical resection, and 72 months (SE = 6.90) in TAE combined with resection.
      CONCLUSIONS: Discrepancies do exist in therapeutic effect of different subtypes
      of HCC. In this study, clear cell HCC was more sensitive to TAE than other
      subtypes, and, in contrast, small cell HCC and poorly differentiated or
      undifferentiated HCC were of lower sensitivity to TAE.

PMID- 11593565
TI  - Surgical treatment of trigeminal neurinomas.
AB  - OBJECTIVE: To investigate the best surgical approach for the removal of
      trigeminal neurinomas (TNs). METHODS: A retrospective analysis of 75' patients
      with TNs in Huashan Hospital was carried out. RESULTS: In the early group (1978
      1984), a series of conventional intradural approaches were used; in the late
      group (1985-1995), an epidural approach via the skull-base craniotomy was used.
      Total tumor removal was achieved in 58% (20/35) of patients in the early group
      and 80% (32/40) in the late group (P < 0.025). Temporary and permanent cranial
      nerve morbidity were 62.7% and 37% in the early group and 28.1% and 10% in the
      late group (P < 0.001). CONCLUSION: The best microsurgical approach for the
      removal of trigeminal neurinomas except those confined to the posterior fossa is
      epidural approach or epidurotransduro-transtentorial approach via the skull-base
      craniotomy.

PMID- 11593566
TI  - Combination of intraoperative embolization with surgical resection for treatment
      of giant cerebral arteriovenous malformation.
AB  - OBJECTIVE: To reduce the risk of surgical resection of giant arteriovenous
      malformation (AVM) (> 6.0 cm) and prevent normal perfusion pressure breakthrough
      (NPPB) for lowering the postoperative mortality. METHODS: During the operation
      under barbiturate anesthesia, the proximal end of the feeding arteries were
      ligated at first, and 0.5 ml isobutyl 12-cyanoacrylate (IBCA) with 0.5 ml 5%
      glucose was injected into the vessels towards the AVM, then the malformed vessels
      were resected totally. Postoperative digital subtraction angiography of the four
      vessels was performed in all patients. RESULTS: 50 patients with giant AVM
      survived after operation, only 6 (12.0%) had transient neurological dysfunction
      and 44 (88.0%) recovered after a follow-up of 6-36 months. No patient suffered
      from normal perfusion pressure breakthrough (NPPB). CONCLUSIONS: The embolization
      could block the arteriovenous shunts sufficiently to decrease the blood flow away
      from the normal areas of the brain so as to prevent the incidence of intra- and
      postoperative rebleeding, especially in NPPB. Therefore, the combination of
      intraoperative embolization with surgical resection is an effective strategy in
      the treatment of giant cerebral AVMs, which make it operable for those used to be
      regarded as inoperable cases.

PMID- 11593567
TI  - Circumferential resection and "Z"-shape plastic end-to-end anastomosis of canine
      trachea.
AB  - OBJECTIVE: To prevent anastomotic stricture of the trachea. METHODS: Forty young
      mongrel dogs, weighing 5-7 kg, were randomly divided into two groups:
      experimental group and control group, with 20 dogs in each group. Four tracheal
      rings were removed from each dog. In the experimental group, two "Z"-shape
      tracheoplastic anastomoses were performed on each dog, one on the anterior wall
      and the other on the membranous part of the trachea. In the control group, each
      dog received only simple end-to-end anastomosis. Vicryl 3-0 absorbable suture and
      OB fibrin glue were used for both groups. All dogs were killed when their body
      weight doubled. RESULTS: The average sagittal stenotic ratio were 1.20 +/- 0.12
      for the experimental group and 0.83 +/- 0.05 for the control group. The average
      cross-sectional area stenotic ratio were 0.90 +/- 0.12 and 0.69 +/- 0.09 and T
      values were 8.71 and 4.57 for the two groups (P < 0.01). CONCLUSION: "Z"-shape
      tracheoplasty is superior to simple end-to-end anastomosis in preventing
      anastomotic stricture of canine trachea.

PMID- 11593568
TI  - Immunohistochemical study of P75NGFR in Hirschsprung's disease.

PMID- 11593569
TI  - Recurrent haemoptysis secondary to tracheopathia osteoplastica.

PMID- 11593570
TI  - Pleomorphic adenoma of the larynx: report of two cases.

PMID- 11593571
TI  - Investigation of long-term preservation of pancreatic islets.
AB  - OBJECTIVE: To develop a method for maintaining viability and function of islets
      of Langerhans during the long-term preservation. METHODS: We encapsulated Wistar
      Furth (WF) rat islets in hydrophilic macrobeads (diameter 6-8 mm) made with
      agarose and collagen, then preserved them at 37 degrees C in a humidified
      atmosphere of air and 5% CO2 for different time, and compared unencapsulated
      islets with encapsulated islets for their insulin secretion capability in vitro.
      At the same time, we have investigated their viability and insulin secreting
      function in vivo. RESULTS: Initially, there was no statistically significant
      difference in the insulin secretion values between the encapsulated and
      unencapsulated WF rat islets. While the unencapsulated islet insulin secretion
      decreased significantly within 2 weeks, the preserved and encapsulated islets
      maintained their viability and ability of insulin secretion for 40 weeks. In the
      in vivo study, the diabetic state was reversed in 92.8% of recipients
      transplanted with preserved macroencapsulated islets. The mice maintained
      normoglycemia for 157.6 +/- 49.3 days, at which point these macrobeads were
      retrieved. Glucose tolerance curves in the recipient mice were similar to those
      of normal mice. CONCLUSIONS: These results indicate that it is a good method for
      long-term preservation of islets by encapsulating islets in agarose and collagen,
      and then culturing them at 37 degrees C in a humidified atmosphere of air and 5%
      CO2 before transplantation.

PMID- 11593573
TI  - Amplified fragment length polymorphism analysis on D5S436 locus and its
      application to linkage analysis in gene diagnosis of asthma.
AB  - OBJECTIVES: To detect the polymorphism of D5S436 locus, and to carry out an
      amplified fragment length polymorphism (Amp-FLP) genotyping linkage analysis in
      asthma families. METHODS: Allele and genotype frequencies of the high polymorphic
      D5S436 locus were determined in 92 unrelated Chinese individuals by using
      polymerase chain reaction (PCR). The amplified fragments were separated by
      denaturing polyacrylamide gel electrophoresis and silver staining techniques.
      RESULTS: Eight alleles and 22 genotypes were observed in this population. The
      heterozygosity was 78.26%. The polymorphism information content (PIC) was 0.76.
      Amp-FLP genotyping linkage analyses were carried out in four asthma families,
      demonstrating that the locus was inherited according to Mendel's law and had a
      clear result. CONCLUSION: The PIC of D5S436 is high in Chinese individuals, so it
      could be used as a genetic marker of asthma in Chinese and might be useful in the
      gene diagnosis of asthma.

PMID- 11593572
TI  - Reversal of aberrant splicing of beta-thalassemia allele by antisense RNA in
      vitro and in vivo.
AB  - OBJECTIVE: To investigate the reversal of aberrant splicing of beta-thalassemia
      allele (IVS-2-654 C-->T, beta 654) by antisense RNA in vitro and in vivo.
      METHODS: The vector expressing antisense RNA which targeted against the aberrant
      splice sites of beta 654 pre-mRNA was constructed in pcDNA3, and then used to
      repair the defective splicing of the mutant pre-mRNA in an in vitro transcription
      and splicing system, as well as in HeLa beta 654 cells and cultured beta 654
      erythroid cells by lipid-mediated DNA-transfection method. The effect of the
      antisense RNA was identified by RT-PCR mediated mRNA quantitative assay as well
      as globin chain microbiosynthesis. RESULTS: The antisense RNA decreased the
      aberrant splicing product and restored the correct splicing pattern in vitro and
      in vivo efficiently. In the in vitro transcription and splicing system, the level
      of normally spliced mRNA [beta/(beta + beta*)] increased from 0.25 to 0.60. In
      cultured HeLa beta 654 cells, the level of beta/(beta + beta*) increased from
      0.07 to 0.43 on the 15th day after transfection. In cultured beta 654 erythroid
      cells, the level of mRNA [beta/(beta + beta*)] increased from 0.19 to 0.58 on the
      8th day after transfection in beta 654/beta 654 erythroid cells, from 0.02 to
      0.38 in beta 654/beta 41-42 erythroid cells, and from 0.45 to 0.83 in beta
      654/beta A erythroid cells, respectively. Correspondingly, the ratios of globin
      chain (beta/alpha) biosynthesis increased from 0.16 to 0.52 on the 8th day after
      transfection in beta 654/beta 654 erythroid cells, 0.05 to 0.36 in beta 654/beta
      41-42 erythroid cells, and 0.42 to 0.81 in beta 654/beta A erythroid cells,
      respectively. The splicing pattern did not show significant changes as compared
      to the untreated, as well as to the control antisense fragment. CONCLUSIONS:
      Antisense RNA transcribed from the expression vector described here could
      efficiently suppress the aberrant splicing pattern of beta 654 mutant mRNA and
      restore the correct splicing pathway in vitro and in vivo, leading to the
      improvement of globin chain biosynthesis in thalassemic cells. Our antisense
      strategy provides an alternative approach to the gene therapy of beta
      thalassemia.

PMID- 11593574
TI  - Gene polymorphisms of the renin-angiotensin system in essential hypertension.
AB  - OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) gene,
      angiotensinogen (AGT) gene and angiotensin II receptor 1 (AT1R) gene are
      implicated in Chinese essential hypertension (EH). METHODS: The case-control and
      haplotype-based haplotype relative risk (HHRR) study consisted of 169 essential
      hypertensive subjects (HT), 152 normotensive controls (NT) and 62 families. The
      polymorphisms of insertion/deletion (I/D) allele of ACE gene and the
      microsatellite allele of AT1R gene were determined in DNA extracted from
      peripheral blood leukocytes by polymerase chain reaction (PCR). The variants of
      AGT gene were screened by PCR-single strand conformation polymorphism (PCR-SSCP)
      analysis and further identified by cloning and sequencing. RESULTS: The
      significant association between EH and D allele of ACE gene was found (P < 0.05).
      The difference of the microsatellite allele distribution of AT1R gene between HT
      and NT groups was statistically significant (P < 0.005). By contrast, the
      distribution of A-20C genotype of AGT gene was almost identical in HT and NT
      groups. No significant linkage disequilibrium was observed between A-20C and
      M235T in AGT gene. CONCLUSIONS: D allele of ACE gene might correlate with a
      predisposing factor for EH. The microsatellite allele of AT1R gene might be
      linkage disequilibrium with an unidentified variant that contributes to the
      development of EH. A-20C of AGT gene is not a major genetic determinant of EH.

PMID- 11593575
TI  - All-trans retinoic acid reduces intimal thickening after balloon angioplasty in
      atherosclerotic rabbits.
AB  - OBJECTIVE: To investigate the effects of oral administration of all-trans
      retinoic acid (ATRA) on inhibition of intimal thickening after balloon
      angioplasty in the rabbit iliac artery atherosclerotic model. METHODS: Iliac
      atherosclerosis was induced in 24 rabbits, and balloon angioplasty was performed.
      At angioplasty, 24 rabbits were randomly divided into four groups (n = 6 per
      group): Group 1: controls not receiving oral ATRA administration; Group 2:
      receiving oral ATRA (0.6 mg.kg-1.d-1) administration beginning 1 week prior to
      angioplasty and continuing for 4 weeks; Group 3: receiving oral ATRA (0.6 mg.kg
      1.d-1) administration beginning immediately after angioplasty and continuing for
      4 wk; Group 4: receiving oral ATRA (0.6 mg.kg-1.d-1) administration beginning 1
      wk after angioplasty and continuing for 4 wk. Values of cross-sectional area,
      ratio of intimal/medial area and thickness were determined by a computer-based
      morphometric system, and cell proliferative activity was assessed by 3H-thymidine
      incorporation. RESULTS: Both the cross-sectional area and the ratio of
      intimal/medial area and thickness were significantly reduced by ATRA
      administration compared with control group (P < 0.01). The inhibitory effect is
      less potent when ATRA is administered 1 week before angioplasty. The ATRA
      inhibitory effect when administered 1 week after angioplasty is not different
      significantly form that when administered immediately after angioplasty. The 3H
      thymidine incorporation was also decreased in ATRA-treated rabbits compared with
      controls (P < 0.01). CONCLUSIONS: Oral ATRA administration can be effective in
      inhibiting intimal thickening after balloon angioplasty. It is reasonable that
      ATRA should be administered immediately after angioplasty.

PMID- 11593576
TI  - A rapid one-step method of EIA for detection of circulating antigen of
      Schistosoma japonicum.
AB  - OBJECTIVE: To establish a highly sensitive serologic method for detecting the
      circulating antigen of Schistosoma japonicum for the diagnosis of this disease
      and the evaluation of drug therapy effect. METHODS: A set of complex support made
      of polyvinyl-chloride (PVC) film slide, adsorbed with specific antibody, was used
      to test serum samples collected from cases with schistosomiasis japonica, by
      adding specific enzyme conjugate and substrate tetra-methyl benzidine (TMB) with
      3% H2O2 in 10:0.1, developed or prepared in our laboratory. Tests were carried
      out with the set on cases with malaria, paragonimiasis, clonorchiasis, visceral
      leishmaniasis and cysticercosis as well as normal individuals as control. Serum
      sample of 50 microliters was used in each test and reacted with reagents at room
      temperature for 30 minutes. The color of positive reaction was blue while
      negative reaction was colorless. RESULTS: Positive rate among cases with
      schistosomiasis japonica was 100% (45/45) in acute stage, 94.8% (530/559) in
      early chronic stage and 52.4% (66/126) in late stage. False positive reaction was
      found neither among all normal individuals (0/513), nor among cases of 155 with
      malaria, 120 with clonorchiasis, 24 with visceral leishmaniasis and 110 with
      cysticercosis, except one among 29 cases with paragonimiasis (1/29). CONCLUSIONS:
      The rapid one-step enzyme immunoassay (EIA) to detect circulating schistosome
      antigen (CSA) has been well established in our laboratory with high sensitivity
      and good specificity as well as reproducibility. The reaction result can be read
      easily even in field conditions without power supply. Moreover, the assay is time
      saving, simple to handle and suitable for the diagnosis of schistosomiasis
      japonica and evaluation of drug therapeutic effect in practice in the control
      program of the disease.

PMID- 11593577
TI  - Suppressing effect of substance P receptor antagonist on sound evoked potentials
      recorded from the guinea pig cochlea.
AB  - OBJECTIVE: To investigate the regulation of SP in the cochlea function. METHODS:
      Ten adult guinea pigs were used as experimental animals. The perilymph space of
      the guinea pigs cochlea was perfused with artificial perilymph solution
      containing 1 microgram/microliter SP receptor antagonist (D-Arg1, D-Pro2, D
      Trp7,9, Leu11)-SP (1-11) at a rate of 2.5 microliters/min for 10 min while
      monitoring cochlear potentials evoked by 4 kHz tone burst. RESULTS: The perfusion
      of SP antagonist resulted in a suppression of the compound action potential of
      the auditory nerve (CAP, N1-P1), a prolongation of the N1 latency at threshold
      and suprathreshold levels, an elevation of the CAP threshold. CONCLUSIONS: These
      results suggest that SP might play a role as a transmitter or modulator in the
      cochlear function.

PMID- 11593578
TI  - Repair of stricture of cervical esophagus with platysma myocutaneous flaps.
AB  - OBJECTIVE: To observe the effect of repairing stricture of the cervical esophagus
      with platysma myocutaneous flaps. METHODS: Fifteen patients with stricture of the
      cervical esophagus were treated by repair with platysma myocutaneous flaps. The
      causes of stricture included anastomotic stenosis of the cervical esophagus after
      colon graft transplantation due to esophageal caustic injury (12 patients),
      anastomotic stenosis after stomach transposition due to resection of the upper
      esophageal cancer (2), and stricture caused by limited erosive injury of the
      cervical esophagus (1). The lengths of stricture were about 3.5-4.5 cm. The
      stricture was incised longitudinally. The platysma myocutaneous flaps about 4 cm
      5 cm x 6 cm-7 cm were resected and were transposed to repair the stricture.
      RESULTS: All flaps survived and no death or serious complications occurred after
      operation. All patients gained normal functions in swallowing food. CONCLUSION:
      Repairing stricture of the cervical esophagus with platysma myocutaneous flaps is
      simple, safe and effective.

PMID- 11593579
TI  - Postoperative radiotherapy for stage I thymoma: a prospective randomized trial in
      29 cases.
AB  - OBJECTIVE: To determine the effect of postoperative radiotherapy on stage I
      thymoma. METHODS: Twenty-nine patients with stage I thymoma younger than 65
      years, treated between August 1981 and January 1996 were included in this study.
      All patients were randomly assigned into two groups: surgery alone (13 patients)
      and surgery with postoperative radiotherapy (16). Staging was based on the
      surgical and pathologic criteria that the tumor had a complete capsule and
      without capsular invasion microscopically. Adjuvant radiotherapy was started
      within 4 weeks after surgery. Megavolage radiation, using the isocentric
      technique, was administered through an anterior field and/or two anterior oblique
      wedge fields. For the patients with lymphocytic predominant type, the dose was 50
      Gy in 25 daily fractions for 5 weeks; for the patients with epithelial cell type
      or mixed type, the dose was 60 Gy in 30 daily fractions for 6 weeks. The survival
      rates were estimated by the Kaplan-Meier method. RESULTS: There was no recurrence
      and metastasis in either group. No acute and late radiological injuries were
      found among the patients receiving radiotherapy postoperatively. The 5-year and
      10-year survivals were both 92% for the patients treated by surgery alone.
      However, the survival rates for patients who received radiotherapy were both 88%.
      There was no difference in the survivals in these two groups. Of the 3 died
      patients, 1 died of myasthenia gravis and 2 of intercurrent illness. No
      significant correlation was found between myasthenia gravis and radiotherapy.
      CONCLUSIONS: Postoperative radiotherapy is unnecessary for the patients with
      stage I thymoma. No relation is found between radiotherapy and myasthenia gravis.

PMID- 11593580
TI  - Interstitial brachytherapy using iridium-192 for malignant brain tumors: clinical
      results.
AB  - OBJECTIVE: To determine the effects and toxicity of interstitial brachytherapy
      using iridium-192 on brain malignant gliomas. METHODS: Between January 1992 and
      January 1995, 56 patients with anaplastic astrocytoma and glioblastoma multiforme
      were treated with stereotactic brachytherapy using temporary high-activity
      iridium-192 sources. RESULTS: The median survival for patients receiving
      brachytherapy was 28 months. The survival rates at 1, 2, 3 years were 92.8%,
      83.9% and 71.4% respectively. CONCLUSIONS: Brachytherapy may improve the control
      of local tumor and prolong the survival, when used in deep malignant brain
      gliomas, by temporary implanted high doses of iridium-192 sources.

PMID- 11593581
TI  - Swine model of arterial bifurcation aneurysm.
AB  - OBJECTIVE: To create an arterial bifurcation aneurysm model in swine and evaluate
      it with digital subtraction angiography (DSA). METHODS: Ten swine were used for
      constructing the arterial bifurcation aneurysm models. Seven pigs underwent
      subsequent intraarterial DSA. Both surgical procedure and transarterial
      angiography were carried out under anesthesia with mechanical ventilation after
      tracheal intubation. RESULTS: Bifurcation aneurysms were surgically created in
      ten animals. After surgical procedure, 2 pigs died from aneurysmal rupture and
      one died of anesthetic overdose. DSA was performed in all other 7 animals and it
      demonstrated 6 patent aneurysms and one occluded. Three of the 6 patent
      bifurcation aneurysms were wide-necked and 3 were narrow-necked. CONCLUSION:
      Arterial bifurcation aneurysm model can be successfully constructed in swine. It
      will provide us with an in vivo model to observe and develop therapeutic devices,
      teach endovascular techniques, and study aneurysmal hemodynamics.

PMID- 11593582
TI  - Dose-related effect of irradiation on circadian rhythm of cellular messengers in
      neural and immune system of mouse.
AB  - OBJECTIVE: To explore toxic effect of gamma-irradiation on circadian rhythms of
      cAMP and cGMP in signal pathway between the central nuclei and peripheral
      lymphocyte. METHODS: 60Co gamma-ray of 0.5 Gy and 5.0 Gy was applied to groups of
      mice at each circadian timepoint of a day. 24 hours after the irradiation, the
      pineal and suprachiasmatic nuclei (SCN) were removed, and the T lymphocytes in
      blood were separated by a step-centrifugal and nylon-filter treatment, for
      measurements of cAMP and cGMP by using the RIA procedure. The results were
      expressed as circadian rhythms of the cAMP/cGMP ratio derived from the Cosinor
      analysis. RESULTS: The daily average cAMP/cGMP ratio in cells of SCN, pineal,
      serum and lymphocyte changed according to the dose of irradiation at which the
      mice were exposed. The high dose of 5 Gy increased the ratio, and the low dose of
      0.5 Gy decreased the ratio. There was a significant difference of cAMP/cGMP
      levels between the irradiated and the control groups, as well as between CT00:00
      and CT12:00 of a day. In addition, the peak phases of the cAMP/cGMP ratio at the
      low-dose groups appeared in advance from about 2 to 8 hours, whereas those at the
      high-dose groups were delayed from about 3 to 6 hours in comparison to that of
      the normal mice. CONCLUSION: Toxic effect of gamma-irradiation on the cAMP/cGMP
      circadian rhythm in the central nuclei and peripheral lymphocyte could be
      characterized by a low-dose hormesis.

PMID- 11593583
TI  - Urinary cross-linked N-telopeptides of type I collagen and bone metabolic
      diseases.
AB  - OBJECTIVE: To evaluate the type I collagen cross-linked N-telopeptide (NTx)
      levels in human urine as an indicator of bone resorption rate in different ages,
      sex and in bone metabolic diseases. METHODS: Urinary NTx was determined by
      immunoassay in 591 Beijing healthy subjects aged from 0 to 86 years and 379
      patients with bone metabolic diseases. RESULTS: The levels of urinary NTx were
      significantly higher in children than in adults (P < 0.001) and higher in boys
      than in girls (P < 0.01) and increased 1.4-2.2 times in postmenopausal females
      than in men and premenopausal women. Urine NTx had a positive linear correlation
      with urine HOP/Cr (r = 0.778, P < 0.01) and Ca/Cr ratio (r = 0.320, P < 0.01),
      and a negative linear correlation with age (r = -0.523, P < 0.01) and lumbar
      spine BMD (r = -0.426, P < 0.01). The levels of urine NTx increased for 3.6 times
      in pregnancy, 1.5 times in osteoporosis, 1.9 times in fragility fracture, 3.6
      times in chronic renal failure, 2.1 times in rickets and 7.2 times in multiple
      myeloma compared to age matched controls. CONCLUSIONS: NTx in urine is a specific
      and sensitive indicator of bone resorption and is able to distinguish normal
      premenopause from late osteoporotic patients. NTx could be used as diagnostic
      information about metabolic bone diseases, and to monitor antiresorptive therapy.

PMID- 11593584
TI  - Factors involved in the neuronal death during postischemic reperfusion:
      experimental study in rabbits.
AB  - OBJECTIVE: To explore the main pathogenic factors in the development of neuronal
      death during normothermic reperfusion in rabbits. METHODS: Ninety-six New Zealand
      rabbits were randomly allocated into two groups: group I served as non-ischemic
      controls; group II served as postischemic normothermic reperfusion models.
      Complete cerebral ischemia was induced by the four-vessel model for 30 minutes.
      After ischemia, rabbits in group II were further divided into three subgroups
      according to the duration of reperfusion: subgroup A, 30 minutes; subgroup B, 180
      minutes and subgroup C, 360 minutes. Twenty-eight biochemical parameters in the
      brain were measured, and neuronal changes were observed by histomorphological
      assessment. Neurons of 12 regions were differentiated into four types: type A
      (normal), type B (mildly damaged), type C (severely damaged) and type D
      (necrotic). Bivariate correlate analysis between the levels of biochemical
      parameters and the percentages of each type of neurons was carried out. RESULTS:
      The main parameters involved in the progressive decrement of type A neurons were
      VIP, beta-EP, PGI2, T3, T4 and Na+, K(+)-ATPase; in the increment of type B were
      beta-EP and TXB2; in the increment of type C were GLU and TXB2/PGI2 respectively;
      in the stepwise increment of percentages of type D neurons were T4, Na+, K(+)
      ATPase, GLU, T3 and VIP (P < 0.05). CONCLUSION: The main factors involved in the
      development of neuronal death during postischemic normothermic reperfusion in
      rabbits include hypermetabolism, deactivation of Na+, K(+)-ATPase, release of
      excitatory amino acids and disorder of neuropeptides.

PMID- 11593585
TI  - Expression of endothelial cell IgG Fc receptors and markers on various cultures.
AB  - OBJECTIVE: To determine and compare the expression of endothelial cell IgG Fc
      receptors (Fc gamma R) and markers on various kinds of cultures. METHODS: Human
      breast microvascular endothelial cells (HMVEC), human aortic endothelial cells
      (HAEC), human umbilical vein endothelial cells (HUVEC) and canine aortic
      endothelial cells (CAEC) were stimulated with cytokines tumor necrosis factor
      alpha (TNF-alpha) and interferon-gamma (IFN-gamma). The binding of anti-Fc gamma
      receptor (Fc gamma R) type I, II and III antibodies was measured using an enzyme
      linked immunosorbent assay (ELISA). The constitutive expression of endothelial
      cell markers was examined using anti-von Willebrand factor antibodies, Dil-low
      density lipoprotein (Dil-Ac-LDL) and fluorescein isothiocyanate (FITC)-labeled
      ulex europaeus agglutinin-1. RESULTS: The binding of anti-Fc gamma R II was
      significantly increased by the simultaneous stimulation with TNF-alpha and IFN
      gamma on all three types of human endothelial cells (ECs), but not on canine
      endothelial cells. Enhanced Fc gamma R II expression was most significant when
      human ECs were cultured in endothelial cell basal medium (ECBM). However, the
      expression of Fc gamma R II on CAECs could not be induced by human cytokines even
      after they were cultured in ECBM for 3 passages. Endothelial cells also showed
      diversity for the constitutive expression of classic markers. CONCLUSIONS: This
      study demonstrate that cytokines TNF-alpha and IFN-gamma enhance low-affinity Fc
      gamma R expression on human endothelial cells in vitro. The results indicate that
      heterogeneity of endothelial cells exists not only on constitutive expression but
      also on stimulative expression.

PMID- 11593586
TI  - Augmentation of antitumor effect of adenovirus-mediated CD suicide gene therapy
      by cotransfer of interleukin 2 gene in melanoma-bearing mice.
AB  - OBJECTIVE: To investigate the antitumor effect of combined adenovirus encoding E.
      coli cytosine deaminase (AdCD) and adenovirus encoding murine interleukin 2 (AdIL
      2) on murine melanoma. METHODS: C57BL/6 mice were inoculated s.c. with B16F10
      melanoma cells and 3 days later received injections of AdCD and/or AdIL-2 at the
      site of tumor inoculation followed by administration of 5-flurocytosine (5FC) 300
      mg/kg per day for 10 days. RESULTS: Mice receiving AdCD/5FC/AdIL2 therapy
      developed tumors more slowly and survived much longer when compared with mice
      treated with AdCD/5FC, AdIL2, AdlacZ/5FC, or PBS. Immunological analysis
      illustrated that combined treatment could enhance NK activity and CTL activity.
      Flow cytometry demonstrated that AdCD/5FC/AdIL2 therapy increased the expression
      of MHC-1 and CD80 molecules on freshly isolated tumor cells. The CD4+ and CD8+ T
      cell infiltration in the tumor increased significantly after the combined
      therapy. CONCLUSIONS: Our data showed that combined transfer of CD suicide gene
      and IL-2 gene could inhibit the tumor growth more significantly. The increased
      specific and non-specific antitumor immunity might be responsible for the
      enhanced therapeutic effect.

PMID- 11593587
TI  - Antibody response to E2 glycoprotein induced in mice by immunization with plasmid
      DNA containing sequence derived from a Chinese genotype III/2a isolate of
      hepatitis C virus.
AB  - OBJECTIVE: To induce antibody response against E2 glycoprotein derived from a
      Chinese genotype III/2a isolate of hepatitis C virus (HCV) in BALB/C mice by
      plasmid DNA-based immunization. METHODS: Plasmid p3W14 containing E2/NS1 gene
      derived from a Chinese genotype III/2a isolate of HCV, which was verified to
      express 70 kDa E2 glycoprotein in NIH3T3 cells, was used for direct intramuscular
      injection in BALB/C mice. Specific antibody to E2 glycoprotein was detected by
      recombinant E2 protein. RESULTS: Specific anti-E2 antibody could be detected in
      mice inoculated with p3W14(5/6). Titer of antibody ranged from 1:15 to 1:120.
      CONCLUSION: Successfully inducing anti-E2 antibody in mice by plasmid DNA-based
      immunization containing E2/NS1 gene from a Chinese genotype III/2a isolate of HCV
      is the first time in China.

PMID- 11593588
TI  - Holistic approach to health education on AIDS.
AB  - OBJECTIVE: To identify a method for health education using the example of an
      educational seminar on AIDS prevention and control at Hebei Medical University in
      China, 1994. METHODS: Our goal is the theoretical formulation of a unified
      community approach for problem solving through the combination of the self
      regulative approach and the case analytical approach. "Quality improvement",
      "essential quality" and "human ecosystems" provide the basic ideas for better
      understanding the integration of culture, science and technology within the
      "cultural norm". RESULTS: The present seminar was successfully organized for
      Chinese medical students based on the theme of "living with AIDS". Through this
      program, we identified that self regulative and case analytical approach were
      major issues for holistic approach to health education. We also identified that a
      community approach provides the scientific basis for health education in the
      community. CONCLUSIONS: The present paper generates a healthcare paradigm for
      surveillance in health/medical education. Through a better understanding of
      community approach, we related "community care" (emphasizing self, mutual,
      professional and institutional care) to the "practical norm"; and "preventive
      epidemiology" (emphasizing the unification of quality and quantity, as well as
      systems and population) to the "research norm".

PMID- 11593589
TI  - Diffusion MRI studies of experimental animal models and patients with stroke.
AB  - PURPOSE: This overview summarises the diffusion magnetic resonance imaging (MRI)
      results both from the experimental animal model studies and clinical
      investigations in acute cerebral ischemic stroke. DATA SOURCES: An English
      literature searched using MEDLINE (1990-1997). STUDY SELECTION: Over 80 papers
      and reviews published in the last eight years and our partial results were
      selected. RESULTS AND CONCLUSIONS: Diffusion weighted magnetic resonance imaging
      (DWI) has been extensively used to study acute cerebral ischemia both in
      experimental animal models and in patients. DWI yields signal intensity contrast
      modulated by water molecular self-diffusion. By recording a series of DWI with
      different amplitudes of the displacement encoding gradient, the apparent
      diffusion coefficient (ADC) can be quantitatively mapped. DWI combined with
      quantitative ADC mapping can provide earlier and more precise evaluation of the
      ischemic zones. However, the biophysical mechanisms behind the decreased ADC in
      acute cerebral ischemia are still not fully understood.

PMID- 11593590
TI  - Hot spot mutations of hepatitis B virus pre-C/C gene and its promotor in Chinese
      patients and the clinical implications.
AB  - OBJECTIVE: To study if the functions of C gene and its promotor are related to
      the pathogenesis of hepatitis B and to describe their hot spot mutations in
      Chinese patients. DATA SOURCES: We have studied this subject in recent years. A
      mini-review is based on some unpublished works. DATA SELECTION: The sequence data
      of C gene and core promotor (cp) of hepatitis B virus (HBV) were analysed in the
      asymptomatic carriers (AsC) and the patients of hepatitis with various severity.
      RESULTS: Pre-C A1896 mutation occurred in 67% of anti-HBe-positive and 38% of
      HBeAg-positive cases. All were chronic infections. In C gene, 8 missense
      mutations in the segment of codon 48-60, and 28 in codon 84-101 were found, more
      in severe patients. The cp mutations of nt 1762 and nt 1764 occurred more in
      HBeAg-negative than in positive cases (49% vs 20%), and more in patients than in
      AsC (56% vs 10%). CONCLUSIONS: A1896 often occurred in nature infection course.
      The cp and clustering C gene mutations would more frequently lead to prolonged
      active infection and advanced liver diseases.

PMID- 11593591
TI  - Clinical hereditary characteristics in nasopharyngeal carcinoma through Ye
      Liang's family cluster.
AB  - OBJECTIVE: To investigate the incidence of nasopharyngeal carcinoma (NPC) and the
      clinical characteristics in this family through a long-term follow-up, and to
      seek the hereditary factor of NPC. This research was also designed to provide
      some clinical data for etiological study. METHODS: A genealogical tree of Ye
      Liang's family was drawn and reported in 1972 after a complete survey. Further
      follow-up from that time to 1997 was performed. Human leucocyte antigens (HLA)
      were investigated, and physical follow-up was done in domestic members of this
      family. For oversea members of this family, correspondence follow-up was
      performed. RESULTS: In the last 25 years, the incidence of malignancies in Ye
      Liang's family increased from 10 cases to 18 cases, and incidence of NPC
      increased from 9 cases to 15 cases. In this family, not only multiple
      malignancies have been found in the second generation, but also NPC has been
      found in the third generation. HLA-[A2-B46] haplotype was correlated with
      occurrence of NPC. CONCLUSIONS: Dominant racial predilection and family cluster
      in NPC implied that NPC is a heredity-related cancer which might involve
      multifactorial disorders in carcinogenesis. Further research on etiology of NPC
      should be focused on hereditary factor. Detection of inherited factors should be
      performed for forecast of carcinogenesis and reduction of NPC occurrence.

PMID- 11593592
TI  - Sternal cleft and ectopia cordis: a case report.

PMID- 11593593
TI  - The impact of codon 54 variation in intestinal fatty acid binding protein gene on
      the pathogenesis of diabetes mellitus in Chinese.
AB  - OBJECTIVE: To investigate whether or not the intestinal fatty acid binding
      protein gene (FABP2)-Ala54Thr variation is related to non-insulin dependent
      diabetes mellitus (NIDDM), obesity, dyslipidemia and glucose stimulated insulin
      secretion (GSIS) in Chinese. METHODS: The FABP2-Ala54Thr variation was detected
      by PCR/Hhal digestion in 231 Chinese subjects (116 with normal glucose tolerance
      (NGT), 54 with impaired glucose tolerance (IGT) and 61 with NIDDM). Plasma
      glucose, insulin and C-peptide levels before and after 75 g glucose load as well
      as fasting lipid profile were determined. RESULTS: (1) The Ala54 and Thr54 allele
      frequencies in Chinese were 0.71 and 0.29 respectively; (2) The FABP2-Ala54Thr
      variation was neither associated with fasting and post-challenged plasma glucose
      levels nor with NIDDM; (3) This variation was neither associated with fasting
      lipid profile nor with obesity; (4) The IGT subjects with genotype Thr54(+)
      (Thr54 homozygotes and heterozygotes) had lower fasting, 2-hour and total C
      peptide levels and smaller AUC representing lesser C-peptide secretion after
      glucose challenge than those with genotype Thr54(-) (Ala54 homozygotes) (P =
      0.04, 0.03, 0.01 and 0.01 respectively). The serum insulin levels changed in the
      same tendency. CONCLUSIONS: The glucose stimulated insulin secretion (GSIS)
      reserve of islet beta-cells is more limited in subjects with FABP2-Thr54(+)
      genotype than in those with FABP2-Thr54(-) genotype. It suggests that FABP2-codon
      54 variation might contribute to the insufficient insulin secretion in the
      development of NIDDM in Chinese.

PMID- 11593594
TI  - [Elevating the standards for the treatment of mass burn casualties].

PMID- 11593595
TI  - [Implementation of "four-early principle" to raise the successful rate in mass
      burn casualties].
AB  - OBJECTIVE: To evaluate the feasibility and result of "four-early principle" in
      the treatment of mass burn casualties. METHODS: During the last 12 years, a total
      of 155 burn patients were admitted in 18 groups, and the following principles
      were implemented; early rapid fluid resuscitation during shock stage for delayed
      resuscitation patients; early tracheostomy to assist air passage humidification
      and lavation for moderate and severe inhalation injury; planning escharectomy and
      grafting during shock stage in patients with extensive deep burns; emphasizing
      early stage enteral nutritional support. RESULTS: The successful rate of
      treatment was raised, and the incidence of complications decreased in mass
      casualties with serious burn after implementing early stage treatment principles.
      CONCLUSION: The application of "four-early principle" on the treatment of mass
      burn casualties is feasible and effective.

PMID- 11593596
TI  - [Treatment of mass burns].
AB  - OBJECTIVE: Present paper aims at summing up the experience from 42 cases over a
      four year period(1993-1997) in ten events of mass burn casualties. METHODS: 42
      cases were analyzed retrospectively, in whom 15 cases sustained III degree burn
      over 50% TBSA. Among them 7 cases had III degree burn over 70% and 3 cases with
      III degree burn over 90%. RESULTS: One case (70% TBSA) died of acute respiratory
      distress syndrome on third postburn day. Another (III degree 70%) died of acute
      renal failure on seventh postburn day. The remaining 40 cases were successfully
      cured. CONCLUSION: Experiences gained in burn care in these ten mass casualties
      included: sending forward the medical expertise to the site of disaster;
      airlifting to accelerate transportation, adequate resuscitation in shock stage;
      early massive excision of eschar and skin grafting; control of burn infection;
      prevention of Curling ulcer hemorrhage, emphasis on supportive therapy; and the
      establishment of a skin bank.

PMID- 11593597
TI  - [Experiences of early management of mass burn casualties].
AB  - OBJECTIVE: Inquire into the effective method of treatment to mass burn
      casualties. METHODS: The experiences of 22 batches of mass burns (403 cases) were
      reviewed. RESULTS: 1. The receiving hospital should take effective measures for
      initial care, and report to the higher health department. 2. Health department
      should send additional specialists to the hospital if necessary, and a leader
      should be appointed. 3. Ambulances with special pass or helicopter should be
      deployed to ensure dispatch of the helpers. 4. Emphasis on local hospital's
      initial treatments, including fluid resuscitation, establishment of an adequate
      airway, early wound management to prevent and premature dissolution of eschar. 5.
      Proper triage of patients, and severe burn patients should be hospitalized to
      burn units with adequate facilities. 6. Transportation: Patients can be
      transferred along where there are good transportation facilities, with fluid
      resuscitation, on the other hand, when transportation if poorly developed,
      transfer the patients after fluid resuscitation until the general condition
      becomes stable. CONCLUSION: 1. Mass burn casualties can be handled with
      satisfactory results if emergency care and professional treatment are well
      organized. 2. Mass burn casualties are usually caused by human errors, therefore
      they can be prevented.

PMID- 11593598
TI  - [The scapular free flap crossing the dorsal midline].
AB  - OBJECTIVE: A large defect needs a large flap to repair. This clinical study was
      to explore the possibility and safeness of transferring the extended scapular
      free flap. METHOD: We have used the transverse scapular flap to reconstruct large
      defects in the mandibular or cervical region in 8 patients. The flap was designed
      to cross the midline of the back as far as 15 cm. The largest flap measured 31 x
      34 cm. RESULTS: Of the 8 flaps, six survived completely; local epidermal necrosis
      appeared in two. CONCLUSION: The free scapular flap supplied by a single
      circumflex scapular vascular pedicle can be safely extended beyond the midline of
      the back. The flap axis is the horizontal branch of the circumflex scapular
      vessel.

PMID- 11593599
TI  - [Repairing the defects of volar surface of distal finger with a reverse insular
      fascial flap of dorsum of juxta positioned digit].
AB  - OBJECTIVE: To introduce a method for one-stage repair of skin defects of the
      volar surface of distal finger or fingers. METHODS: The reverse fascial flap was
      designed and created on the dorsum of the juxta positioned digit, and it was then
      rotated 180 degrees to cover the defects of the volar surface of the distal
      finger. Since May 1992, a total of 20 reverse fascial flaps were used to treat 14
      patients. RESULTS: All flaps survived except one with partial necrosis. Follow-up
      of one half to one year showed satisfactory results functionally and
      cosmetically. The finger is plump but not swollen. CONCLUSION: The method is easy
      and effective. The surgical treatment requires short time and causes little pain.
      The flap has good blood supply, suitable thickness, softness and resistance to
      wear and tear.

PMID- 11593600
TI  - [Clinical applications of the anterolateral skin flap and the fascial flap in the
      lower leg].
AB  - OBJECTIVE: To introduce the applied anatomy, operative method and clinical
      application of the anterolateral skin flap and fascial flap of the lower leg.
      METHODS: Anatomic dissection was performed on 14 adult cadavers' legs and one
      amputated lower limb. The origin, course and distribution of cutaneous branches
      of the superficial peroneal vessels were traced. Four types of anterolateral
      flaps were designed in the lower leg including the island skin flap, the island
      fascial flap, the rectangular flap, and the cross-leg flap. Since 1988, twenty
      six cases of leg defects(21 patients), chronic osteomyelitis of the tibia(3
      cases) and defects on the back of the opposite heel and ankle(2 cases) were
      treated with the operative methods. RESULTS: All the flaps survived. Primary
      healing occurred in 23 and secondary in 3 cases. Twenty cases were followed-up
      for 4 months to 5 years. The flaps were growing well, the tibia fracture healed 3
      months after the treatment and the chronic osteomyelitis of tibia had no
      recurrence. CONCLUSION: This flap is a useful method for repairing various
      defects in the leg and adjacent regions. It is simple, safe and reliable in
      manipulation and has minimal influence to the donor site.

PMID- 11593602
TI  - [The study and application of the alar cartilage ring in the treatment of
      deformities of unilateral cleft lip nose].
AB  - OBJECTIVE: To explore the possible pathogenesis and to look for effective
      reconstructive procedures of unilateral cleft lip nose. METHODS: The author has
      had a detailed comparative study by comparing the cartilaginous skeleton of 20
      normal cadaver specimens with that of one unilateral cleft lip stillborn, as well
      as intraoperative findings of 24 clinical patients. RESULTS: There are two alar
      cartilaginous rings, namely alar cartilaginous fibrous ring and alar
      cartilaginous muscular ring, in external nose. Both rings are hypoplastic in the
      cleft lip patients. According to the findings, the author designed and applied a
      new operation procedure to reconstruct alar cartilage ring for 24 patients from
      1994 to 1997. An acceptable short-term results were found. CONCLUSION: Alar
      cartilaginous fibrous ring and alar cartilaginous muscular ring are very
      important anatomic structures to maintain the shape of the lower part of the
      nose. Hypoplasia of these rings is an important factor leading to deformities of
      the nose. It is very important to reconstruct alar cartilage ring for the
      patients with unilateral cleft lip nose.

PMID- 11593601
TI  - [Orbicularis oculi muscle suspension and orbital septum fixation in
      blepharoplasty].
AB  - OBJECTIVE: The study is to correct all the deformities of the lower eyelid. There
      is a regressive keletonization of the orbit as the soft-tissue covering of the
      lower eyelid skin and orbicularis oculi descend downward due to loss of tone, and
      the orbital fat herniates through a weakened septum orbital, resulting in an
      infraorbital crease. METHODS: We suspend the orbicularis oculi muscle and fix the
      orbital septum in blepharoplasty. RESULTS: This method has been used in 32
      patients with satisfactory results in recent years. CONCLUSION: The technique can
      improve all the deformities of the baggy eyelids and achieve long-lasting
      youthful countenance.

PMID- 11593603
TI  - [Study of the local anatomy and clinical practice about rhytidectomy of
      nasolabial fold].
AB  - OBJECTIVE: A technique is introduced to improve the operative result of
      rhytidectomy of the nasolabial fold. METHODS: Regional anatomy was studied on 10
      adult cadavers together with histological examinations of tissue sections to
      investigate the formation mechanism of the nasolabial fold. 13 patients were
      operated on using a new technique of nasolabial fold rhytidectomy. RESULTS:
      Prolonged and repeated movements of the facial mimetic muscles produce a shearing
      force between the skin-subcutaneous tissue and the SMAS-mimetic muscles, causing
      relative motion of adjacent tissues with different structure at the site of the
      nasolabial fold, thus producing the nasolabial fold. In clinical application of
      the finding, the nasolabial folds of 13 patients were corrected with remarkable
      early and long-term results postoperatively. CONCLUSION: The operation should be
      performed between SMAS and the subcutaneous tissue. SMAS should be incised along
      the zygomatic major muscle. The fibro-fatty zygomatic pad should be replaced
      anatomically and the zygomatic ligament be reconstructed.

PMID- 11593604
TI  - [The periareolar incision technique for reduction mammoplasty].
AB  - OBJECTIVE: A technique is introduced to reduce the scar of classic reduction
      mammoplasty. METHODS: Two concentric circles were designed with the nipple in the
      centre. The skin between the two circles was deepithelized. Then the glandular
      tissues situated mainly in the lateral superior quadrant are resected. Finally,
      round block suturing is made. Eight patients were operated on with this method.
      RESULTS: The operative results were satisfactory with inconspicuous periareolar
      scar. CONCLUSION: Periareolar round block reduction mammoplasty is a simple,
      practical and easy method.

PMID- 11593605
TI  - [Hard palate lengthening by palatal suture expansion: an experimental study in
      dogs].
AB  - OBJECTIVE: Scar contraction and lack of bony support for soft palate in
      traditional surgery of cleft palate are main causes of a shortening soft palate
      and its developmental deficiency. The wound and scar also lead to aberration of
      facial growth. In order to resolve these problems, lengthening of hard palate by
      transverse palatal suture expansion was studied. METHODS: Six mongrel dogs of 8
      week age were used in the study. Amalgam markers were implanted in the hard
      palate of the animal. A NiTi-shaped memory alloy (NiTi-SMA) arch wire with a
      force level of 600 g was used to expand the palato-maxillary suture with a
      retention period of 8 weeks. The dogs were killed at the age of 36 weeks. Serial
      X-ray and cephalometry were used to investigate the changes. RESULTS: The suture
      expansion was generally completed in 4 weeks. The distance of separation of the
      palatine bone and maxilla was 1.0 to 1.5 cm. Premaxilla became protrusive
      significantly at the beginning of the suture expansion, then restored gradually
      to its original position. The length of hard palate increased 4.6 to 5.9 mm by
      dry skull measurement. CONCLUSION: Hard palate could be permanently lengthened
      anterior-posteriorly by transverse palatal suture expansion.

PMID- 11593606
TI  - [Histological study and stereologic analysis of membranous versus endochondral
      onlay bone grafts].
AB  - OBJECTIVE: The experimental study was to determine the differences in changes in
      the onlay bone grafts of different embryonic origin. METHODS: The study was
      designed to compare the potential for appositional bone growth in membranous and
      endochondral onlay grafts in New-Zealand rabbits and a rhesus monkey. Results
      were assessed with volumetric measurement, histological examinations and
      stereologic analysis with double-fluorochrome labeling technique. RESULTS: For
      the membranous and endochondral bone grafts, the volumetric retention rate was
      (78.4 +/- 3.5)% and (56.0 +/- 5.1)% respectively. The mineralization apposition
      rate (MAR) was (3.6 +/- 0.8) microns/d and (0.92 +/- 0.33) micron/d; the osteoid
      seam width (OSW) was (14.56 +/- 2.69) microns and (7.38 +/- 2.20) microns; the
      tetracycline uptake rate(TUA) was (91.22 +/- 2.69)% and (51.28 +/- 4.11)%,
      respectively. CONCLUSION: 1. It was found that the membranous bone graft
      maintained its volume to a significantly greater extent than the endochondral
      bone graft; 2. Membranous bone grafts exhibited higher survival rate and greater
      activity than endochondral bone grafts; 3. Different changes were also found in
      the two recipient sites. There was more powerful bone regenerative reaction in
      the recipient bed of the membranous bone graft than the endochondral one.

PMID- 11593607
TI  - [Changes in TGF-beta 1 and type I, III procollagen gene expression in keloid and
      hypertrophic scar].
AB  - OBJECTIVE: The expression of mRNA for TGF-beta 1, type I, III procollagen in
      keloid and hypertrophic scar was investigated in order to elucidate the
      pathogenesis of and the difference between keloid and hypertrophic scar. METHOD:
      Dot-blot hybridization analysis was used to examine the type I, III procollagen
      and the expression levels of steady-state mRNA. In situ hybridization allowed
      direct assessment of the distribution of TGF-beta 1 mRNA in the tissue. RESULTS:
      1. Our study indicated that the expression level of mRNA for TGF-beta 1
      significantly increased in keloid and hypertrophic scar compared with normal scar
      and normal skin. 2. In keloid tissues, type I precollagen mRNA expression was
      selectively increased. However, in hypertrophic scar, type I and III collagen
      mRNAs expressions were simultaneously increased. CONCLUSION: TGF-beta 1 plays an
      important role in the pathogenesis of keloid and hypertrophic scarring. It
      implicates that distinct molecular mechanisms are operative in the development of
      keloid and hypertrophic scarring.

PMID- 11593608
TI  - [Effects of intralesional injection of kenalog or interferon alpha-2b on PDGF BB
      gene expression in situ of hypertrophic scars].
AB  - OBJECTIVE: The study is to determine whether kenalog or interferon alpha-2b
      inhibits fibroblast growth in hypertrophic scars through decreasing PDGF. METHOD:
      Six patients with hypertrophic scars received intralesional injection of kenalog
      or interferon alpha-2b. On the 3rd and 7th day after injection, scar samples from
      each patient were collected and PDGF mRNA expressions in situ were studied.
      RESULTS: 1. On the 7th day after intralesional injection of kenalog or interferon
      alpha-2b, expressions of PDGF BB mRNAs decreased significantly (P < 0.01).
      However, on the 3rd day the expressions of PDGF BB mRNAs of the intralesional
      injected area and non-injected area were not significantly different (P > 0.05).
      2. Gene expressions of PDGF BB in situ were higher in hypertrophic scars than in
      normal skin. CONCLUSION: The mechanism of kenalog or interferon alpha-2b in
      ameliorating hypertrophic scar is to reduce mitosis and prohibit proliferation of
      fibroblasts in hypertrophic scars by inhibiting PDGF gene expression.

PMID- 11593609
TI  - [Performing escharectomy following "clinical guidelines" in extensively burned
      patients during burn shock stage].
AB  - OBJECTIVE: To verify the practicability of performing escharectomy on extensively
      burned patients during shock stage following the clinical guidelines only.
      METHOD: Sixty-five burn patients with total body surface area(TBSA) over 30%
      received resuscitation to prevent and treat burn shock without hemodynamic
      monitoring. Clinical indexes of optimal resuscitation, such as a urine volume 80
      to 100 ml/h, heart rate around 100 to 110/min, respiration rate 20 to 24/min,
      significant alleviation of thirst, sense of nausea and vomiting, clear mentality,
      Hb < or = 150 g/l and Hct < or = 0.50 were adopted as guidelines, under which
      thirty-three patients underwent escharectomy and grafting during burn shock stage
      (group A). For comparison, other 32 patients received escharectomy 96 hr after
      injury(group B). The incidences of sepsis and MODS were analyzed. Plasma samples
      from 12 patients in group A and 9 patients in group B were assayed at interval
      for LPS, TNF, IL-6 and IL-8. RESULTS: All 33 patients in group A were in stable
      condition, and the incidence of sepsis was lower (34.4%) than that in group
      B(56.3%). The incidence of MODS and the mortality of patients in group A was
      lower than those in group B. Levels of LPS, TNF, IL-6 and IL-8 in plasma were
      lower in group A as compared with those in group B. CONCLUSION: The results show
      that escharectomy could be performed during shock stage under clinical guidelines
      with reasonable safety.

PMID- 11593610
TI  - [Effects of NGF and CNTF on NO level in brain of burn rats].
AB  - OBJECTIVE: To investigate the injurious effects of NO to the brain and protective
      effect of NGF and CNTF following burn injury in rats. METHODS: Following
      intubation of the lateral cerebroventricle, the rats were divided into four
      groups:sham burn, burn, burn + NGF, burn + CNTF. The contents of NO in various
      parts of brain in rats with 30% TBSA third degree scald were measured. RESULTS:
      The contents of NO were increased in burned rats. NGF and CNTF could lower the
      contents of NO. CONCLUSION: The brain injury caused by burns may be associated
      with increase of NO. The protective effect of NGF and CNTF on the brain of burn
      rats may be related to lowering of NO.

PMID- 11593611
TI  - [A study of the relationship between dynamic blood rheologic changes and the
      fluid resuscitation in burn patients].
AB  - OBJECTIVE: To further study the relationship between hemor rheologic changes and
      fluid resuscitation in patients with burn and treatment of anemia after burns.
      METHODS: 238 case of burn patients were divided into four groups. In which
      patients with major burn were allocated to group C and D according to different
      methods of fluid resuscitation and treatment of anemia. RESULTS: Abnormal
      hemorrheologic parameters could be corrected when transfusion of fresh whole
      blood and traditional herb medicines were given within 24-48 hours after burn
      injury. CONCLUSION: Dynamic observation of hemorrheologic changes is one of
      important index in monitoring burn shock and guiding fluid resuscitation. Blood
      transfusion and traditional medicine can improve abnormal blood rheologic
      parameters, effectively correct anemia when given early.

PMID- 11593612
TI  - [The time course and tissue distribution of endotoxin in rats after thermal
      injury].
AB  - OBJECTIVE: To observe the time course and tissue distribution of endotoxin, and
      to evaluate the potential role of local endotoxin in mediating multiple organ
      damage following burns. METHODS: Wistar rats were subjected to a 35 percent full
      thickness scald injury. They were grouped according to time of sacrifice: no
      burn, and 12, 24, 48, 72 hours postburn. Tissue specimens from liver, kidneys,
      lungs and intestine were aseptically harvested to determine tissue endotoxin
      levels. In addition, blood samples were obtained for measurement of organ
      function parameters. RESULTS: It was found that endotoxin levels in liver, spleen
      and lungs increased markedly after thermal injury, with the highest level in
      liver. Meanwhile, serum GPT, GOT, CK-MB levels, and pulmonary
      myeloperoxidase(MPO) activities markedly elevated after scald injury, reaching a
      maximum between 12 and 24 hours. Intestinal diamine oxidase(DAO) activities
      tended to decrease at various time points postburn. In addition, there were
      highly positive correlations between pulmonary endotoxin levels and MPO
      activities, and also between renal endotoxin levels and serum Cr values.
      CONCLUSION: Burn injury per se can result in gut-derived endotoxin translocation
      which is mainly distributed to the liver, spleen and lungs. Endotoxin accumulated
      in local sites may play an important role in mediating multiple organ damage
      secondary to major burns.

PMID- 11593613
TI  - [The effect of intestinal ischemia/reperfusion on increased sensitivity to
      endotoxin and its potential mechanism].
AB  - OBJECTIVE: To investigate the effect of intestinal ischemia/reperfusion injury
      (I/R) on increased sensitivity to endotoxin and its potential mechanism(s).
      METHODS: Sprague-Dawley rats underwent 45 minutes of superior mesenteric artery
      occlusion followed by reperfusion. Twelve hours after reperfusion, endotoxin
      (Escherichia coli LPS, 1.5 mg/kg) was injected intravenously and rats were killed
      12 hours later for measurement of organ function parameters. Also, in vitro study
      was performed to determine LPS-induced tumor necrosis factor (TNF)release in
      whole blood. RESULTS: LPS injection after I/R resulted in marked hemodynamic
      dysfunction and multiple organ damage(P < 0.01), while no significant or only
      minor changes in organ function parameters were observed in both I/R and LPS
      groups. In whole blood, monoclonal antibody to CD14 significantly blocked the
      release of TNF at low LPS concentration (< or = 10 ng/ml), and this response was
      dose dependent. Moreover, TNF release in LPS-stimulated whole blood obtained
      after I/R was inhibited to a significantly greater degree than that in baseline
      blood samples or sham-operation group(P < 0.05-0.01). CONCLUSION: Splanchnic
      artery occlusion followed by reperfusion could lead to increased sensitivity to
      the subsequent LPS challenge, which may be associated with a shift toward CD14
      dependent mechanism(s).

PMID- 11593614
TI  - [An experimental study of metacresol burn].
AB  - OBJECTIVE: To study the characteristics of metacresol burn. METHODS: Metacresol
      of 99.6% was used. The animals were randomly separated into control group,
      excision group, topical SD-Ag group, saturated sodium sulfate wet compress group,
      and warm running water flushing group. RESULTS: It was proved that metacresol
      could not only cause deep burns to skin but also penetrate skin and to produce
      impairment of functions of the main internal organs of the body, as shown by
      abnormalities in blood BUN, GPT, GOT, GGT, and AKP. Pathological changes were
      also found in the liver, heart, brain, kidney, and skin with light and electron
      microscopy. CONCLUSION: Through comparison of the four different treatment
      methods for metacresol burns, it is concluded that excision of the wound followed
      by skin grafting should be done as early as possible to minimize absorption of
      the chemical. Topical application of SD-Ag or sodium sulfate wet compress, and
      flushing with running water can alleviate direct injury to skin. Drugs to protect
      the heart, liver, and kidney should be used for a longer period than usual.

PMID- 11593615
TI  - [The change in bacterial flora and antibiotic resistance of bacteria of burn
      patients in our hospital during 1986-1996].
AB  - OBJECTIVE: In this article we investigated and analyzed the pathogenetic bacteria
      of burn infection and their drug resistance in recent 5 years from 1991. METHODS:
      The patients are divided into 2 groups. The 1st group is from June 1986 to May
      1991, and the 2nd group is from June 1991 to June 1996. Blood culture and burn
      wound bacteria culture were done, and bacteria and their drug sensitivity were
      analyzed. RESULTS: In blood culture, Micrococcus had risen to rank the top
      (21.6%), while Staphylococcus aureus fell to rank the third. Among these G+ cocci
      comprised 56.5%, and G- bacilli 30.1%. In burn wound culture, Pseudomonas
      aeruginosa with rate of 18.1% was still in the 1st place. Enterobacter cloacae
      was in the 2nd place with the rate of 13.1%. Among these G- bacilli comprised
      58.6%, G+ cocci 35.3%. Micrococcus enterobacter cloacae, Pseudomonas maltophilia,
      fecal Staphylococcus and candida albicans increased remarkably. CONCLUSION: The
      changes of pathogenetic bacteria of burn infection and bacteria drug resistance
      have certain relations with the wide usage of broad spectrum antibiotics such as
      cefazidime and imipenem.

PMID- 11593616
TI  - [Uses of homologous dermis graft in burn wounds].

PMID- 11593617
TI  - [Reconstruction of anus in low rectum cancer operation].
AB  - OBJECTIVE: While low rectum cancer being resected with Mile's operation, the anus
      was reconstructed in situ simultaneously. METHODS: Thirty cases of artificial
      anus were perfectly reconstructed in situ with transferring of the gracilis and
      invaginating of the end of the sigmoid for the outer and inner sphincter of the
      anus. The artificial rectum valve was used for the rectum angle. RESULTS: The
      rate of excellent and good operative results reached 90.63%. CONCLUSION: The
      results show that this method is suitable for radical operation of low rectum
      cancer and functional incapacitation of the anus from other diseases as well.

PMID- 11593618
TI  - [Determination of scalp ER and AR of patients with male pattern baldness and the
      effects of hair transplantation on them].
AB  - OBJECTIVE: To study the role of sex hormone receptor capacity of the scalp in
      male pattern baldness(MPB). METHODS: Estrogen receptor(ER) and androgen
      receptor(AR) assays were performed using fluorescent steroid hormone conjugate
      technique (FSHCT) in hairness and bald scalp in 8 patients with MPB. Changes of
      ER and AR capacity in recipient and donor sites of hair transplantation in MPB
      scalps were examined. RESULTS: The percentage of AR staining cells in the outer
      root sheath, sebaceous gland and bulb papilla of the lesional scalps was
      significantly higher than that of hairness scalps (P < 0.01). The percentage of
      ER positive cells in the outer root sheath of lesional scalps increased
      significantly (P < 0.01). CONCLUSION: Changes of contents of sex hormone
      receptors(SHR) in some sensitive area of the scalp induce MPB.

PMID- 11593619
TI  - [Progress in the treatment for nasolacrimal duct obstruction].

PMID- 11593620
TI  - [The role of beta-ray induced fibroblasts apoptosis on the inhibition of
      hypertrophic scar].
AB  - OBJECTIVE: To investigate the role of beta-ray induced apoptosis of the
      fibroblasts on the inhibition of hypertrophic scar. METHODS: A series of patients
      with hypertrophic scar were grouply treated with a certain dose beta-ray. A
      liopic sample was taken in each patients. Its was then examined with MTT[3-(4,5
      dimethylthiazol.-2-yl)-2,5-dipheny1 terazolium-bromide] technique for deciding
      the inhibition rate of the fibroblasts, with electron microscope technique, DNA
      agarose gel electrophoresis and flow cytometry for evaluating the morphological
      and biochemical characteristics of the fibroblast. RESULTS: The beta-ray
      radiation resulted in significant inhibition of the fibroblast. The features of
      fibroblast apoptosis(e.g.: apoptotic bodies, DNA ladders band and hypodiploid DNA
      peak) could be seen in the group with lower does (10 Gy). The features of
      fibroblast necrosis could also be found in the group with higher does(20 Gy).
      CONCLUSIONS: The beta-ray radiation could have the effect for inhibiting the
      proliferation of scar-derived fibroblast, but with dose dependence. It could be
      used for the treatment and(or) the prevention of hypertrophic scar.

PMID- 11593621
TI  - [The study of expression and distribution of PCNA in hypertrophic scar tissue].
AB  - OBJECTIVE: To analyze the expression and the distribution of proliferation cell
      nuclear antigen (PCNA) in hypertrophic scar for identifying its certain
      characteristics during the fibroblast proliferation. METHODS: Bioptic samples
      were taken form 12 cases of hypertrophic scar, 8 cases of matured scars and 20
      cases of controlled normal skin. Each sample was immunohistochemically stained
      and examined with monoclonal antibody[PCNA(pc10)] technique. The level of PCNA
      expression was decided for evaluation of the fibroblast proliferation. RESULTS:
      The level of PCNA in the hypertrophic scar(45.4 +/- 12.3) was significantly
      higher than mature scar(17.4 +/- 6.2), also normal skin(13.5 +/- 4.1, P < 0.01).
      But, there was no significant deference between the matured scar and the normal
      skin. The PCNA intracellular particles may sometimes be bound in the
      keratinocytes and the fibroblasts of some connective tissue. CONCLUSION: The
      fibroblast proliferation in the hypertrophic scar has kept a high level. During
      the process of hypertrophic scar formation it may play an important role.

PMID- 11593622
TI  - [A study on the expressions and the correlation of TGF-beta and alpha-SMA in
      scars].
AB  - OBJECTIVE: To detect the expressions of TGF-beta(TGF-beta 1, TGF-beta 2, TGF-beta
      3) and alpha-SMA and to investigate the probable effects of TGF-beta in the
      formation of hypertrophic scars as well as the expression of alpha-SMA in the
      scars. METHODS: 28 samples of hypertrophic scars, 19 samples of flat scars and 16
      samples of normal skin have been examined immunohistochemically for the
      expressions of TGF-beta and alpha-SMA. Then a statistical and correlative
      analysis was carried out among the groups based on patient age, sex and scarring
      time. RESULTS: 1. TGF-beta and alpha-SMA have no expression in normal skin, but
      have varied expressions in hypertrophic scars and flat scars. 2. TGF-beta 1, TGF
      beta 2 and alpha-SMA expressed highly in hypertrophic scar in comparison with
      normal skin and flat scar with a significantly statistical difference (P < 0.01).
      3. There was a high expression of TGF-beta 3 in the flat scar and some
      hypertrophic scar that were from the female group or the scar over one year. 4.
      There was no statistical difference between the groups of teenage and adults. 5.
      The correlative analysis of TGF-beta to alpha-SMA demonstrated that the algebraic
      value of TGF-beta 1 + TGF-beta 2 - TGF-beta 3 correlates positively to alpha-SMA
      (r = 0.57). TGF-beta 3 correlates negatively to alpha-SMA(r = -0.80).
      CONCLUSIONS: 1. The formation and contraction of scar result from the synergic
      effects of TGF-beta 1, TGF-beta 2 and TGF-beta 3. TGF beta 1, TGF-beta 2
      correlate the hyperplasia and contraction of scar, whereas TGF-beta 3 correlates
      the maturing of scar. To suppress the expression of TGF-beta 1, TGF-beta 2 or
      promote the expression of TGF-beta 3 would be beneficial to prevention of
      hyperplasia and contraction of scar. 2. It is reasonable to postulate that the
      female have stronger resistance to scar hyperplasia in that they have stronger
      expression of TGF-beta 3, which deserves further clinical observation and
      investigation. 3. The age has no influence on the expression of TGF-beta and
      alpha-SMA.

PMID- 11593623
TI  - [The effects of PDGF-AB on pro alpha 1 (III). mRNA expression of fibroblasts].
AB  - OBJECTIVE: To investigate the mechanism of PDGF-AB to promote wound healing and
      its role during the process of scar formation. METHODS: In vitro cultured
      fibroblasts of human normal skin and hypertrophic scar were treated with PDGF-AB.
      The expression of Pro alpha 1 (III) mRNA of the fibroblasts was evaluated by in
      situ hybridization technique. RESULTS: PDGF-AB could increase Pro alpha 1 (III)
      mRNA expression of fibroblasts of both normal skin and hypertrophic scar in a
      dose-dependent manner. However, the effect of PDGF-AB on hypertrophic scar
      fibroblasts was stronger. CONCLUSIONS: PDGF-AB may promote wound healing by
      stimulating extracellular matrix synthesis, e.g. collagen. PDGF-AB may also play
      a role in scar formation through collagen deposition.

PMID- 11593624
TI  - [Applied anatomy of the transverse rectus abdominis musculocutaneous (TRAM) flap
      in relation to the eleventh or twelfth thoracic nerve].
AB  - OBJECTIVE: To observe the distribution of the terminal branches of the eleventh
      and twelfth thoracic nerve(T11, T12) for the anatomical basis and operation key
      points of the transverse rectus abdominis musculocutaneous(TRAM) flap with T11,
      T12. METHODS: The anterior abdominal wall was investigated through anatomical
      dissection in 22 embalmed cadavers. RESULTS: Cutaneous nerve distribution in the
      TRAM flap came mainly from T11, T12. They run obliquely between transverse
      abdominis and obliquus internus abdominis muscle. At the lateral edge of the
      rectus abdominis, they piece the anterior rectus sheath into the muscle. While
      supplying the muscle they pass on to supply the anterior rectus sheath and the
      overlying skin. CONCLUSION: It is possible to preserve T11, T12 in the TRAM flap,
      which would favour rapid return of flap sensation.

PMID- 11593625
TI  - [Exploration of the mechanism of skin expansion].
AB  - OBJECTIVE: In order to explore the mechanism of skin expansion technique (SET).
      METHODS: Domestic dogs were used in this experiment. The epidermal mitotic
      activity, capillary blood flow change of the expanded flap were observed with
      microspectrophotometer and radioactive microsphere technique. RESULTS: 1. The
      epidermis of expanded skin was significantly thicker than that of other groups (P
      < 0.05). 2. The epidermal mitotic activity was elevated significantly(P < 0.01).
      3. The capillary blood flow of expanded flaps increased significantly (P < 0.01).
      CONCLUSIONS: 1. The surplus skin produced by SET is the result of replication,
      not compensation. 2. SET increases skin blood flow, therefore enlarges the
      survival area of an expanded flap.

PMID- 11593626
TI  - [A special software for area and volume measurement and 3D image of skin
      expander].
AB  - OBJECTIVE: A special software for measuring expanded skin area and volume and
      creating a 3D image of skin expander protrusion has been introduced. METHODS: The
      3D coordinates of all the points on the surface were obtained by means of
      interpolation in computer, according to its base, central horizontal and vertical
      sections that should be adopted in advance. This software was programmed with C
      language and performed in Microsoft Windows. RESULTS: The area, volume, and 3D
      image were acquired according to 3D coordinates. The deviation of the software
      measurement was less than 4% of actual sizes at most in our reliability
      demonstration. CONCLUSION: This software, combined with our protocol of
      conversion from tridimensional surface to a plane reported previously, makes up a
      preferable scheme in this field.

PMID- 11593627
TI  - [Relation of venous drainage and inadequate circulation in the rat pedicled TRAM
      flap model].
AB  - OBJECTIVE: To evaluate the circulatory characteristics of the TRAM flap because
      the vascular supply to lateral portion of the conventional TRAM (zone 4)
      occasionally may become compromised resulting in necrosis of fat tissue or
      requiring segmental excision of the poor perfused tissue. METHODS: In this study,
      we designed a rat pedicled TRAM flap model with either inadequate arterial or
      venous circulation. The skin paddle was photographed and the survival areas were
      measured on the tenth postoperative day. RESULTS: The results showed that the
      group with poor arterial inflow of the flap, which resulted from ligation of the
      superior deep epigastric artery, exhibited skin necrosis in zone 1 and 2. Venous
      stasis due to selective ligation of the venous pedicle resulted in necroses of a
      major area in the lateral part of the flap, especially in zone 4. However, venous
      stasis may be alleviated by an additional cutaneous venous return system.
      CONCLUSIONS: Our results demonstrated that conventional rat TRAM flap with poor
      arterial inflow differs from that with venous stasis in terms of manifestations
      and extent of inadequate circulation. Necrosis of the lateral portion of human
      TRAM flaps may therefore be attributed to problems of venous stasis. Such
      problems might then be ameliorated by creating an additional cutaneous venous
      return system.

PMID- 11593628
TI  - [Experimental study of lymph node flap transplantation for treatment of
      lymphedema].
AB  - OBJECTIVE: We investigated the treatment of lymphedema by using lymph node flap.
      METHODS: Upper limbs' lymphedema model in 14 rabbits were divided into two
      groups. They were treated with lymph node flap transplantation and general flap
      transplantation. RESULTS: Lymph node transplantation can reduce lymphedema and
      general flap transplantation can not significantly reduce lymphedema. CONCLUSION:
      Lymph node flap can be used to treat extremity's lymphedema.

PMID- 11593629
TI  - [Experimental study on selective thrombolytic activity of pro-urokinase].
AB  - OBJECTIVE: To evaluate the valve of pro-urokinase as a selective thrombolytic
      agent in microsurgery. METHODS: The levators muscle model in rats was used to
      investigate the effect of pro-urokinase on dissolving ischemic thrombi and
      fibrinogenolytic activities in circulation by local infusion. The tissue
      microcirculation, pathologic appearance of rat lungs and muscles, and general
      fibrinogenolytic activities were observed. RESULTS: The thrombolytic rate of pro
      urokinase was 92.3% (P < 0.05), the positive rate of D-dime was 83.3%(P < 0.05).
      No significant change of alpha 2-PI was observed on general fibrinogenolytic
      activities(P > 0.05). CONCLUSIONS: It is suggested that pro-urokinase can be used
      to dissolve the thrombi in microcirculation of free tissue transplantation
      without affect general fibrinogenolytic activities. It is safe to use pro
      urokinase in free tissue transplantation.

PMID- 11593630
TI  - [One-stage correction of the contracted eye socket and orbitozygomatic
      hypoplasia].
AB  - OBJECTIVE: In order to simultaneous correct the contracted eye socket and
      orbitozygomatic hypoplasia that caused by early ophthalmectomy and radiotherapy.
      METHODS: The one-stage surgical procedure for eye socket reconstruction and bone
      graft coverage included rotation of a postauricular skin flap and a temporal
      fascial flap. Hydroxyapatite implant was inserted as an onlay bone graft
      substitute to enlarge the orbitozygomatic region. RESULTS: In 16 cases using this
      method, the results were satisfactory and encouraging with minor complications.
      CONCLUSION: This procedure is effective for radiated complex deformities in
      paraorbit and eye socket.

PMID- 11593631
TI  - Changing pattern of heart diseases in Shanghai from the 1950s to 1980s.
AB  - OBJECTIVE: To determine the pattern of dynamic change in types of heart diseases
      in the past 4 decades for providing a reference to treatment and prevention of
      heart diseases in China. METHODS: All adult cardiac patients admitted to the
      Zhong Shan Hospital and Hua Shan Hospital from 1948 to 1989 were analyzed. The
      constituent ratio of different heart diseases in the 1950s, 1960s, 1970s and
      1980s was compared. RESULTS: The percentage of heart diseases among medical
      inpatients increased in each of the recent 4 decades, from 9.89%, 15.69%, 20.90%
      to 23.54% respectively. The constituent ratio of different heart diseases
      changed, coronary heart disease constituted the highest proportion, next came
      rheumatic heart disease, and congenital heart disease was in third place.
      Congenital heart disease, myocarditis, cardiac dysrhythmia without organic heart
      disease, cardiomyopathy and endocarditis increased, rheumatic heart disease,
      pulmonary heart disease and hypertensive heart disease apparently decreased;
      syphilitic heart disease could rarely be encountered. CONCLUSION: China is now
      facing a low overall death rate, a long life expectancy and an aging population.
      The incidence of heart diseases increased gradually and patterns of heart
      diseases kept changing. The overall trend is that heart diseases which were not
      related to infection are increasing while heart diseases related to bacterial
      infection are decreasing.

PMID- 11593632
TI  - A comparative study on the effects of low dose of tPA and different regimens of
      intravenous urokinase in acute myocardial infarction.
AB  - OBJECTIVE: To compare the effects of low dose of recombinant tissue-type
      plasminogen activator (tPA) with those of conventional dose of urokinase (UK) and
      assess the influence of different regimens of intravenous UK in patients with
      acute myocardial infarction (AMI). METHODS: Eighty patients with AMI were
      randomized to 50 mg of tPA (Group I; n = 26) using an accelerating approach or
      1.0-1.5 million U of UK (Group II; n = 54). UK was administered as a single bolus
      injection of whole dose (Group IIa; n = 26) or half dose bolus injection followed
      by half dose infusion (Group IIb; n = 28). All patients underwent coronary
      arteriography 90 min after the initiation of intravenous thrombolysis, and the
      infarct-related coronary artery (IRA) patency was evaluated. Cardiac events
      during hospitalization were recorded and predischarge left ventricular function
      was determined by two-dimensional echocardiography. RESULTS: The IRA patency rate
      was significantly higher in Group I (88.4%) than in Group II (53.7%) (P < 0.01).
      Group I patients had less cardiac events during hospitalization (11.5% vs 33.3%)
      and greater improvement in left ventricular function than Group II patients.
      However, these angiographic, left ventricular functional and prognostic
      parameters did not significantly differ between Group IIa and Group IIb.
      CONCLUSIONS: Thrombolysis after AMI with low dose of intravenous tPA exerts
      better angiographic and clinical effects than that with conventional dose of UK.
      The thrombolytic effects of UK were not affected by different regimens of
      intravenous administration of the agent.

PMID- 11593633
TI  - Transvenous pectoral implantation of single lead implantable cardioverter
      defibrillator.
AB  - OBJECTIVE: To report our initial experience of transvenous pectoral implantation
      of single lead implantable cardioverter defibrillator (ICD) in fifteen patients.
      METHODS: Fifteen patients (male 13, female 2, mean age of 51.7 years), including
      dilated cardiomyopathy in 4, hypertrophic cardiomyopathy in 2, coronary artery
      disease in 5 and syncope of unknown etiology in 2, underwent ICD implantation.
      Indications for ICD implantation were ventricular fibrillation (8 patients) and
      refractory ventricular tachycardia (7 patients). All patients had syncope out of
      hospital. The ICD system were Medtronic Jewel active can in 5 patients (Model
      7219C in 2, 7220C in 3) and CPI Ventak PRxIII in 9 patients. For active can,
      shocks were delivered through distal coil to ICD shell and for PRxIII through the
      endotak lead of proximal to distal coil. Successful implantation criteria was 2
      consecutive defibrillation at less than 24 J. RESULTS: All 15 patients had
      successful implantation using single lead ICD system in catheter laboratory. The
      mean defibrillation threshold was 12.8 J (5-15 J) and R wave was 9.9 mV (3.7-14.6
      mV). All devices were of pectoral implantation. No operative and perioperative
      complications occurred. In 7.6 months (1-18 months) of follow-up, 3 patients had
      VT terminated by antitachycardia pacing (ATP) and 1 patient VF terminated by
      shock. CONCLUSION: Transvenous pectoral implantation of single lead ICD is easy
      to perform and has high defibrillation efficacy and should be a preferred
      approach.

PMID- 11593634
TI  - The surgical treatment of lung cancer: a retrospective analysis of 2004 cases.
AB  - OBJECTIVE: To summarise the clinical results of surgical treatment of 2004 cases
      of lung cancer over a period of 33 years and to evaluate the main influencing
      factors for long-term results. METHODS: 2004 patients treated at our department
      were included in this study. The pathological classification proposed and revised
      by WHO in 1982 was used. The TNM (tumour, nodes, and metastasis classification)
      system of staging proposed and modified by UICC (International Union Against
      Cancer) in 1987 was followed. Pearson's Chi-square test was used in comparing
      variables. RESULTS: There were 1571 men and 433 women, with a man to woman ratio
      of 3.6:1. The pathological findings were squamous cell carcinoma (944 cases,
      47.1%), adenocarcinoma (694, 34.6%), small cell carcinoma (167, 8.3%),
      adenosquamous cell carcinoma (78, 3.9%), large cell carcinoma (22, 1.1%),
      alveolar cell carcinoma (17, 0.8%) and miscellaneous carcinoma (82, 4.1%). The p
      TNM staging in 1721 resected cases was: stage 0 (2 cases, 0.1%), stage I (860,
      50%), stage II (407, 23.6%), staging IIIa (396, 23.0%), stage IIIb (35, 2.0%) and
      stage IV (21, 1.2%). The overall resection rate was 85.9% (1721/2004) and the
      complication rate was 15.7% (271/1721). The 30-day mortality was 1.3% (22/1721).
      The 5-, 10- and 15-year survival rates were 38.8%, 31.6% and 21.8%, respectively.
      Factors influencing the long-term survival rate included the nature of resection,
      the mode of resection, presence or absence of lymph gland metastasis, tumour size
      and degree of extension, pathological type and p-TNM staging. CONCLUSIONS:
      Surgery is recommended for stage I, II and IIIa non-small cell lung cancer and
      for stage I and II small cell lung cancer. Meticulous preoperative staging
      process is important. Bronchoplastic resection is recommended to replace
      pneumonectomy whenever the conditions are permissible.

PMID- 11593635
TI  - Diagnosis and treatment of splanchnic artery aneurysms: a report of 57 cases.
AB  - OBJECTIVE: To evaluate the diagnosis and treatment of splanchnic artery
      aneurysms. METHODS: A retrospective study of our case records from 1957 to 1997
      was carried out. Fifty-seven patients with splanchnic artery aneurysms were
      involved in this study with 62 aneurysms, including hepatic aneurysm (14
      patients), gastric and pancreaticoduodenal aneurysm (13), splenic aneurysm (14),
      renal aneurysm (6), superior mesenteric aneurysm (3), inferior mesenteric
      aneurysm (1), truncus coeliacus (3) and epiploic arterial aneurysm (3). Among
      them, 5 patients had multiple aneurysms; 29 had massive bleeding of spontaneous
      rupture into the biliary tract (14 patients), the upper gastrointestinal tract
      (10), and the peritoneal and retroperitoneal cavity (5). RESULTS: Preoperative
      diagnosis was confirmed by arteriography in 37 patients, digital subtraction
      angiography (DSA) in 2, and magnetic resonance angiography (MRA) in 2. Among the
      46 patients who underwent surgical intervention, 9 died. Splanchnic arterial
      embolotherapy was performed in 6 patients. CONCLUSION: Splanchnic artery
      aneurysms have a potential for rupture with life-threatening hemorrhage. Clinical
      assessment of these lesions before operation is very difficult. The most valuable
      examination is selective arteriography of the splanchnic artery (including DSA).
      Surgical treatment is a safe and effective procedure. Embolic therapy may be the
      method of choice for selected splanchnic artery aneurysms. Prognosis of this
      disorder depends on the anatomic location of aneurysms, primary disease and
      general condition of patients.

PMID- 11593636
TI  - A review on studies of smoking and coronary heart disease in China and Hong Kong.
AB  - PURPOSE: To document and review all the published reports on smoking and coronary
      heart disease (CHD) in China and Hong Kong, and to estimate the risks of CHD due
      to smoking. DATA SOURCES: Papers cited in Medline, Chinese Biomedical Literature
      Disc and Chinese Medical Current Contents, references in review papers,
      conference papers and abstracts. STUDY SELECTION: All published reports which had
      findings on smoking and CHD were included. DATA EXTRACTION: Reports on 13 cross
      sectional, 16 case-control and 13 prospective studies were included. Available
      data on risk estimates from 23 studies were extracted and pooled odds ratios (OR)
      and relative risks (RR) were calculated using Mantel-Haenszel's methods. RESULTS:
      In China in 1970s, most results, which were from cross-sectional studies, did not
      show an association between smoking and CHD. In the 1980s, most case control
      studies found an association but the prospective studies did not. In the 1990s,
      there was stronger evidence from prospective studies mainly in men. The relative
      risk was about 1.90 in men and about 2.50-3.50 in women although the 95%
      confidence interval for the latter was wide. Dose response relationships were
      observed in 12 studies. In Hong Kong, there were one cross-sectional and two case
      control studies. CONCLUSIONS: The existing evidence supports that smoking is a
      cause of CHD in Chinese, particularly in men. More data in women are needed to
      quantify the risk more precisely. The risk estimates probably indicate only the
      early stage of a growing tobacco epidemic.

PMID- 11593637
TI  - Relationship between serum antisperm antibodies and anticardiolipin antibodies
      and clinical pregnancy outcome in an in vitro fertilization and embryo transfer
      program.
AB  - OBJECTIVE: To study the influence of maternal immunological factors on clinical
      pregnancy outcome in an in vitro fertilization and embryo transfer (IVF-ET)
      program. METHODS: One hundred and fifty IVF-ET treatment cycles from November
      1995 to November 1996 were studied. The indication for IVF-ET treatment was
      bilateral blocked tubes. Serum antisperm antibodies and anticardiolipin
      antibodies were measured using enzyme-linked immunosorbent assay (ELISA).
      Cleavage rate and successful pregnancy rate in relation to antibody status of
      infertile women after IVF-ET treatment were assessed. RESULTS: Lower cleavage
      rate (64.2% +/- 32.1%) was found in 44 cycles of antisperm antibody seropositive
      women, compared with 84.8% +/- 18.7% in 106 cycles of seronegative women (P <
      0.05). The clinical pregnancy rate was 31.8% in antisperm antibody-positive
      cycles and 20.8% in negative cycles (P > 0.05). The abortion rates of the two
      groups were similar (P > 0.05). Lower pregnancy rate (9.5%) was found in 21
      cycles of serum anticardiolipin antibody-positive group, compared with 26.3% in
      129 cycles of seronegative women (P < 0.05). Of patients with bio-chemical
      pregnancy and no pregnancy, 20.0% and 16.2%, respectively, had seropositive
      anticardiolipin antibody, compared with 5.6% of patients with clinical pregnancy
      (P < 0.05). CONCLUSION: Serum immunological factors may play a part in clinical
      pregnancy outcome in IVF-ET.

PMID- 11593638
TI  - Prevention of intrauterine infection by hepatitis B virus with hepatitis B immune
      globulin: efficacy and mechanism.
AB  - OBJECTIVE: To evaluate the efficacy of hepatitis B immune globulin (HBIG) in
      preventing intrauterine infection by hepatitis B virus (HBV) and to investigate
      its mechanism. METHODS: Forty-eight pregnant women positive for hepatitis B
      surface antigen (HBsAg) were randomly divided into 2 groups. The 34 women in the
      study group were injected with HBIG during pregnancy; the other 14 women were
      controls. Maternal blood samples were taken before HBIG injection and at
      delivery. Neonatal blood samples were taken within 24 hours after birth before
      HBIG and hepatitis B vaccine were given. HBsAg and antibody to HBsAg (anti-HBs)
      were tested by radioimmunoassay. RESULTS: None of the 35 newborns (including 2
      twins) in the study group was positive for HBsAg, but 3 (21%) in the control
      group were positive (P = 0.02). The HBsAg titers in the women in the study group
      decreased after HBIG injection. Of the 35 newborns in the study group, 32 (91%)
      were positive for anti-HBs. CONCLUSION: Systematic injections of HBIG during
      pregnancy may prevent intrauterine HBV infection, the mechanism of which may be
      reduction of maternal HBV virernia and production of fetal passive immunity.

PMID- 11593639
TI  - The relationship between the c-jun mRNA expression and apoptosis of neurons in
      rat brain following perinatal ischemic-hypoxia.
AB  - OBJECTIVE: To investigate the relationship between c-jun mRNA and apoptosis of
      neurons following perinatal ischemic-hypoxia. METHODS: We set up a fetal rat
      model of perinatal ischemic-hypoxia by ligating unilateral uterine horn vessel of
      pregnant Wistar rats (21-day gestation). The contralateral horn vessel was not
      ligated and the fetuses in these uteri served as controls. Rat pups were
      delivered by cesarean section at the end of ischemic hypoxic insult and then the
      rats' brain tissues were collected in different points of time. In situ
      hybridization and TUNEL methods were used to detect the c-jun mRNA expression and
      neural cells apoptosis separately. RESULTS: The expression of c-jun mRNA in brain
      tissues began at 15 minutes, reached the first peak at 1-2 hours after ischemic
      hypoxic insult and reduced gradually after 4 hours and the second peak at 24th
      hour after insult, gradually disappeared till 72nd hour. There were very low c
      jun mRNA expression of hippocampus in the control group 24 h after birth.
      Meanwhile, we observed that the apoptosis of neuronal cells in cerebral cortex
      was much more than that in the control group. CONCLUSION: The increases of
      immediate early gene c-jun expression and the cell apoptosis could be induced by
      perinatal ischemic-hypoxia. The higher expression of c-jun mRNA might induce the
      transcription of its target gene, especially, so called "death related genes",
      which would be a promoter for cell apoptosis.

PMID- 11593640
TI  - Carpal tunnel syndrome: a retrospective analysis of 262 cases and a one to one
      matched case-control study of 61 women pairs in relationship between manual
      housework and carpal tunnel syndrome.
AB  - OBJECTIVES: To get a more comprehensive recognition about carpal tunnel syndrome
      (CTS), especially the manual housework as its risk factor, and to facilitate
      early diagnosis and proper treatment. METHODS: 262 CTS patients (396 CTS hands)
      were analyzed retrospectively. A 1:1 matched case-control study of 61 woman pairs
      in relationship between manual housework and the occurrence of CTS was carried
      out. RESULTS: In 262 CTS patients, 84% were female, and the dominant hand was
      more frequently affected; repetitive and forceful movement of the hand and wrist
      might be associated with CTS. Typical clinical manifestations include pain and
      paresthesia in the median nerve territory, but 75.3% of our 396 CTS hands had all
      five digits involved. Conduction abnormalities appeared selectively in the median
      nerve distal to the wrist. In the case-control study, for manual washing, rolling
      or kneading dough, and knitting woolen sweater, the odds ratios (OR) of CTS
      between high and low intensities were 3.86 (95% confidence interval 1.79-8.33,
      chi 2 = 11.76, P < 0.01), 6.25 (95% confidence interval 2.50-15.63, chi 2 =
      15.21, P < 0.01) and 1.13 (95% confidence interval 0.57-2.22, chi 2 = 0.125, P >
      0.05) respectively; and those between long and short duration (i.e. the number of
      years engaging in these manual housework) were 2.33 (95% confidence interval 0.63
      8.64, chi 2 = 1.6, P > 0.05), 1.88 (95% confidence interval 0.81-4.38, chi 2 =
      2.13, P > 0.05) and 1 (chi 2 = 0, P > 0.05). CONCLUSIONS: The diagnosis of CTS
      requires confirmation of illness history, symptoms and signs with objective
      electrodiagnostic tests. Manual washing and rolling or kneading dough might be
      associated with the onset of CTS.

PMID- 11593641
TI  - Neurotrophic factors increase tyrosine hydroxylase immunoreactive cell density of
      fetal mesencephalic cells.
AB  - OBJECTIVE: To hibernate fetal ventral mesencephalic tegmental (VMT) cells from
      Spraque-Dawley rats E-15 for 5 days at 4 degrees C in either hibernation media
      (HM) or in conditioned hibernation media (CHM) supplemented with trophic factors
      such as epidermal growth factor (EGF 200 ng/ml), basic fibroblast growth factor
      (bFGF 100 ng/ml), recombinant human brain derived neurotrophic factor (rhBDNF 20
      micrograms/ml), recombinant human glial cell-derived neurotrophic factor (rhGDNF
      20 micrograms/ml), fetal calf serum (FCS 9%), or human placental cord serum (HPCS
      10%). METHODS: The percent of cell viability and the density of tyrosine
      hydroxylase immunoreactive (THir) cells in fetal striatal-VMT co-culture were
      determined. RESULTS: The viability of fetal striatal cells (0.8 +/- 0.104) was
      slightly higher than that of fetal VMT cells (0.7 +/- 0.072) at 0-time point
      (F17,1 = 4.677; P = 0.045). After 5 days of hibernation, the viability of fetal
      VMT cells reduced by 30% (F7,1 = 88.493; P < 0.001) in HM. However, THir-cell
      density reduced by more than 90% as compared to the freshly harvested VMT cells
      (F7,1 = 179.944; P < 0.001). CHM with HPCS, bFGF, EGF, BDNF, and GDNF showed
      higher THir-cell density than that of HM or CHM supplemented with FCS (P <
      0.001). CONCLUSION: Supplementation of appropriate trophic factors for hibernated
      fetal VMT cells promotes cell viability and the subsequent expression of THir
      cell density.

PMID- 11593643
TI  - The protective effect of vitamin E on gastric mucosal injury in rats with
      cirrhosis of the liver.
AB  - OBJECTIVE: To evaluate the functional and morphologic features of stomach in
      liver cirrhosis model and the cytoprotective effects of Vitamin E. METHODS:
      Experimental cirrhosis was induced in rats by subcutaneous administration of 0.4
      ml CCl4 (diluted 1:4 with olive oil) per kilogram of body weight twice a week for
      12 weeks. Rats were divided into three groups. Group 1 was control. Group 2
      consisted cirrhotic rats induced by CCl4 and Group 3 cirrhotic rats treated with
      Vitamin E (intramuscularly 100 mg/kg per day during study). At the end of 12
      weeks, gastric mucosal injury was produced by instillation of absolute alcohol
      via an orogastric tube. After 3 hours, each animal was sacrificed. The stomachs
      were macroscopically, microscopically and biochemically analyzed. RESULTS:
      Macroscopic and microscopic area of gastric mucosal injury were significantly
      larger in cirrhotic rats (P < 0.05). Gastric mucosal injury was more serious in
      cirrhotic rats as compared with Group 1. With vitamin E treatment, tissue
      Malondialdehyde (MDA) and glutathione [GSH (X)] levels were significantly lower
      in group 3 as compared with group 2 (P < 0.001). CONCLUSION: Gastric mucosa in
      cirrhotic rats has distinctive histological and functional abnormalities. These
      abnormalities can be reversed by Vitamin E or other antioxidants.

PMID- 11593642
TI  - Killing effect of interleukin-2 and interferon-alpha activated leukemic bone
      marrow in remission on K562 leukemic cells.
AB  - OBJECTIVE: To evaluate the killing effect of interleukin-2 (IL-2) and interferon
      alpha (IFN-alpha) activated bone marrow cells on K562 cells. METHODS: Semi-solid
      colony and 3H-TdR incorporating method were used. RESULTS: Bone marrow from
      leukemia patients in remission was activated in vitro with IL-2 for 3 days. The
      activated bone marrow (ABM) displayed killing effects of 0.31-2.30 logs on K562
      cells. This killing effect was further increased to 0.30-3.15 logs when IFN-alpha
      added with IL-2 to the marrow for activation. IL-2 alone or in combination with
      IFN-alpha showed no inhibition of CFU-GM and K562 cells. Compared with IL-2 or
      IFN-alpha alone, the combination of the two cytokines could more effectively
      maintain the killing effect of ABM on leukemic cells. CONCLUSIONS: IFN-alpha can
      augment the purging effect of IL-2 ABM and combination of the two cytokines can
      effectively maintain the cytotoxicity of ABM.

PMID- 11593644
TI  - Expression of ICAM-1, B7.1 and TPO on human thyrocytes induced by IFN-alpha.
AB  - OBJECTIVE: To detect expression of intercellular adhesion molecule-1 (ICAM-1),
      B7.1 and thyroid peroxidase (TPO) on thyrocyte and study the possible mechanism
      of interferon-alpha (IFN-alpha) in the pathogenesis of autoimmune thyroid disease
      (AITD). METHODS: Thyrocytes were cultured from 6 normal persons. Antigen
      expression on thyrocytes induced by cytokines was examined using
      immunofluorescence staining with flow cytometer. RESULTS: IFN-alpha significantly
      stimulated the expression of ICAM-1, B7.1 and TPO, as compared with those of
      control group. IFN-gamma markedly enhanced the expression of HLA-DR and ICAM-1,
      but not B7.1. Prolactin (PRL) resulted in increased expression of ICAM-1, B7.1,
      as well as overexpression of TPO, which is more significant than that stimulated
      by IFN-alpha. CONCLUSIONS: Thyroid autoimmunity induced by IFN-alpha is
      associated with the expression of ICAM-1, B7.1 and TPO. IFN-gamma could not
      induce the expression of B7.1, therefore it is not an initiator in AITD. In
      addition, we should pay more attention to PRL which possibly plays an important
      role in the initiation and perpetuation of postpartum thyroiditis.

PMID- 11593645
TI  - Cloning and expression of beta 2-glycoprotein 1 recognized by antiphospholipid
      antibodies and its clinical investigation.
AB  - OBJECTIVE: To investigate cloning and expression of beta 2-glycoprotein 1 (beta
      2GP1) recognized by antiphospholipid antibodies and to study the clinical
      significance of anti-beta 2GP1 antibodies in patients with autoimmune disease.
      METHODS: By using reverse transcription-PCR method, two kinds of expression
      plasmid which expressed beta 2GP1 and the fifth domain of beta 2-glycoprotein 1
      (beta 2GP1-D5) proteins respectively were constructed in this study. Their
      antigenic activities were identified by immunoblots using rabbit anti-beta 2GP1
      antibodies. Anti-r beta 2GP1 and anti-r beta 2GP1-D5 antibodies in the 112
      patents were detected by ELISA using r beta 2GP1 and r beta 2GP1-D5 as coating
      antigens. RESULTS: A significant correlation in statistics (r = 0.667, P < 0.01)
      between the levels of anti-r beta 2GP1 and anticardiolipin antibodies (aCL) was
      found. The presence of anti-r beta 2GP1 antibodies was associated with an
      increased frequency of history of thrombosis and/or recurrent abortion. Anti-r
      beta 2GP1 assay provided better specificity than conventional aCL assay. The
      binding of anti-r beta 2GP1 from the sera of patients with antiphospholipid
      syndrome (APS) to r beta 2GP1 was inhibited by r beta 2GP1-D5. Meanwhile, of 28
      patients who had positive anti-r beta 2GP1 antibodies in sera, 27 (96.4%) had
      positive anti-r beta 2GP1-D5 antibodies. CONCLUSION: It is indicated that
      antigenic epitope of beta 2 GP1 might be located in its fifth domain. Detection
      of anti-r beta 2GP1 antibodies may be of potential value for evaluating the risk
      of thrombosis and/or other APS associated symptom.

PMID- 11593646
TI  - Identification of mutation in a candidate gene for hereditary multiple exostoses
      type II.
AB  - OBJECTIVES: To identify possible mutations in our previously cloned candidate
      gene for hereditary multiple exostoses type II (EXT2) in affected members of EXT
      families so as to confirm that it is the disease-causing gene. METHODS: The
      mutation was detected first by single strand conformational polymorphism (SSCP)
      of all coding exons of the candidate gene and then by sequencing analysis.
      RESULTS: After analyzing 37 patients from 20 Chinese EXT families by SSCP and DNA
      sequencing analysis, one 2-bp insertion mutation was identified in this candidate
      gene in affected members of an EXT family. This mutation resulted in the
      frameshift and generated a truncated gene product consisting of 105 amino acids.
      CONCLUSIONS: The identification of the mutation in the candidate gene indicates
      that this novel gene is responsible for EXT2 (one of the disease-causing gene of
      EXT).

PMID- 11593647
TI  - The change of insulin-like growth factor-1 in diabetic patients with neuropathy.
AB  - OBJECTIVE: To evaluate the possible relationship between insulin-like growth
      factor-1 (IGF-1) and diabetic neuropathy (DNP). METHODS: Sixty-nine patients with
      Type 2 non-insulin-dependent diabetes (54 with peripheral neuropathy and 15
      without neuropathy) were observed. Normal controls were 34 non-diabetic persons.
      Diabetic peripheral neuropathy diagnosis was carried out taking into account
      results of NS, ND, NC and AF. After an overnight fast, blood was taken for IGF-1,
      glucose, hemoglobin Alc, C-peptide, and insulin. Plasma IGF-1 was measured by
      radioimmunoassay (RIA) method. RESULTS: The neuropathic group had significantly
      lower levels for IGF-1 (86.43 ng/ml +/- 45.18 ng/ml) compared to normal controls
      (119.68 ng/ml +/- 89.42 ng/ml) (P < 0.05), and to diabetic patients without
      neuropathy (113.75 ng/ml +/- 66.58 ng/ml) (P < 0.05). No significant difference
      was found between diabetic non-neuropathic group and normal control subjects (P <
      0.05). In diabetic subjects there was a positive correlation (gamma = 0.27, P <
      0.05) between IGF-1 and beat to variation in heart rate. There were negative
      correlation between IGF-1 and postprandial blood glucose (gamma = -0.3, P <
      0.05), and aspartic acid translocase (gamma = -0.27, P < 0.05). CONCLUSION: In
      diabetic patients with peripheral neuropathy there are abnormalities of IGF-1
      that may contribute to the pathogeneses of diabetic neuropathy.

PMID- 11593648
TI  - Combating hepatocellular carcinoma with an integrated approach.
AB  - This short review summarizes an integrated approach to new methods of managing
      hepatocellular carcinoma (HCC) developed at our centre. HCC-specific isoforms of
      alpha-fetoprotein were detected by isoelectric focusing and their value in the
      differential diagnosis of early HCC on a background of chronic liver disease has
      been shown. Selective internal radiation therapy using yttrium-90 (90 Y)
      microspheres has been shown to be an effective treatment for inoperable HCC in a
      phase I and II study. A partition model for estimating the radiation doses from
      the 90 Y microspheres to the tumour and the non-tumorous liver during the therapy
      was then formulated, verified by correlating with intraoperative dosimetry, and
      evaluated in clinical settings. This permits 90 Y microspheres to be administered
      safely without the need of an open surgery and a randomized therapeutic
      controlled trial is in progress. Another randomized controlled trial using iodine
      131 Lipiodol as a post-operative adjuvant therapy, aiming at reducing the
      recurrence rate is also on-going. HCC may be more effectively combated with a
      better understanding of its pathogenesis from chronic liver disease.

PMID- 11593649
TI  - Massive lipoma of the scrotum.

PMID- 11593650
TI  - Leptomeningeal carcinomatosis: an unusual cause of headache in bronchial
      carcinoma.

PMID- 11593651
TI  - Unilateral approach to posterior retrocrural coeliac plexus block.

PMID- 11593652
TI  - Non-invasive assessment of myocardial risk and infarct area in canine model of
      myocardial reperfusion by intravenous contrast echocardiography.
AB  - OBJECTIVE: To evaluate the newly developed perfluoropropene-filled echo-contrast
      agent (FCT-188) in non-invasive assessment of risk areas (RA) and infarct areas
      (IA) with intravenous myocardial contrast echocardiography (MCE) in canine model
      of ischemia followed by reperfusion. METHODS: Eight chest-opened Beagle dogs with
      a 90-minute ischemia followed by a 240-minute reperfusion were studied. MCE was
      performed after a bolus injection of FCT-188 (0.025 ml/kg, i.v.) into a
      superficial vein of the forelimb at baseline, 20 minutes after occlusion, and 4 h
      after reperfusion to non-invasively assess the left ventricular myocardium area
      (LVMA), myocardial ischemic risk area (RA), and infarct area (IA) in a short-axis
      view of left ventricle. The accuracy of detecting myocardial perfusion with
      intravenous MCE was further assessed by in vitro myocardial staining of the
      matched cross-sections. Both RA and IA were expressed as percent of LVMA.
      RESULTS: LVMA, RA, IA, and IA/RA ratio were accurately assessed by MCE (LVMA:
      6.60 cm2 +/- 0.76 cm2; RA: 35.7% +/- 6.68%; IA: 21.0% +/- 13.2%; IA/RA: 60.3% +/-
      31.4%; n = 7) as compared with those of the matched cross-section (LVMA: 6.81 cm2
      +/- 0.73 cm2, P = 0.062; RA: 35.3% +/- 9.9%, P = 0.84; IA: 25.10% +/- 14.5%, P =
      0.07; IA/RA: 68.0% +/- 22.2%, P = 0.28, respectively). There was a significant
      correlation of MCE-assessed IA/RA ratio and its corresponding pathologically
      determined finding in vitro (Y = 1.21 x -21.6, r = 0.73, P = 0.015). No
      significant changes of electrocardiogram (ECG), mean artery pressures (MAP),
      pulmonary artery pressures (PAP), and pulmonary artery wedge pressures (PAWP)
      were found between pre- and post-intravenous injection of FCT-188 at each time
      point. CONCLUSION: These indicate that FCT-188 can be used to assess risk areas
      and infarct areas accurately and non-invasively with intravenous MCE in the
      canine model of a 90-minute ischemia followed by a 240-minute reperfusion and
      might have potential significance for non-invasive assessment of myocardial
      reperfusion clinically.

PMID- 11593654
TI  - [Evaluation of the safety of tissue engineering products].

PMID- 11593653
TI  - Detection of group C rotavirus antigen in bile duct and liver tissues of an
      infant with extrahepatic biliary atresia.

PMID- 11593655
TI  - [An initial experiment study on allogenic tissue engineered cartilage].
AB  - OBJECTIVE: To investigate the formation of engineered cartilage in vivo with
      allogenic chondrocytes. METHODS AND MATERIALS: Joint cartilage from ewe embryos
      (Pregnancy: 100 days) was isolated and digested to obtain dissociated
      chondrocytes. Mixed chondrocytes with biomaterials (Pluronic 127) at the density
      50 x 10(6)/ml, then implant the allograft complex subcutaneously. Collect the
      novel tissue every two weeks along for six months, weigh and stain (HE, Safranin
      O, Masson's trichrome) the sample tissues individually to evaluate the
      characteristics of novel tissue. RESULT: Novel cartilage can regenerate in
      allograft animals, with similar histological properties of chondrocytes,
      aminoglycin and collagen distribution to normal cartilage. The novel cartilage
      observed histologically showed apparent surrounding inflammatory cells in two and
      four week and the tissue of cartilage came to mature since the sixth week, with
      less inflammatory reaction, but not disappeared. CONCLUSION: Novel cartilage can
      generate in allograft animals with tissue engineering approach, with certain
      immunoreaction surrounding. Such reaction will be weakened gradually with time.

PMID- 11593656
TI  - [Biomicrocapsule membrane for cell and tissue transplantation].
AB  - OBJECTIVE: To Provide a simple and safe way in protecting living cells from
      immune rejection for transplantation therapies. METHODS: Enclose cells in
      Alginate-poly-l-lysine (APA) biomicrocapsules which have to be satisfied the
      following requirements: 1. biocompatibility, 2. strength, 3. permeability.
      RESULTS: The transplanted cells survived and had prominence therapy function in
      experimental animals. CONCLUSIONS: Biomicrocapsules are feasible tools for cells
      immune-transplantation.

PMID- 11593658
TI  - [Human umbilical cord used for wrapping hydroxyapatite orbital implant--animal
      experiment and clinical observation].
AB  - OBJECTIVE: Hydroxyapatite (HA) sphere is admitted to be the best orbital implant
      today, but it can cause some complications, such as conjunctival erosion and
      implant exposure. The causes of these complications include HA's mechanical and
      chemical stimulation to the conjunctiva. In order to protect conjunctiva against
      HA's invasion, most authors suggest wrapping the HA sphere with some material.
      The wrapping materials usually are autogenous or heterogeneous sclera or fascia.
      These materials are either unavailable or unaccepted by patients. This study was
      made on human umbilical cord tissue as the wrapping material of HA sphere.
      METHOD: Hydroxyapatite spheres enveloped in human umbilical cord tissue were
      inserted in ten rabbits' orbits. At 1, 2 weeks and 1, 2, 3, 6, 8, 10, 12 and 14
      months after implantation, the conjunctival sac was examined. Then the HA sphere
      was removed and examined with a scanning electron microscope. Fifteen patients
      received HA orbital implants enveloped in human umbilical cord from September
      1996 To December 1997. The pre- and post-operative photographs of the sockets,
      the implant motility were analysed. RESULTS: The animal experiment showed that
      the umbilical cord was tightly adherent to the HA sphere and orbital tissue. The
      fibro-vascular tissue gradually invaded the interconnecting pores of the sphere
      after implantation. None of the 15 patients had orbital infection or implant
      extrusion during an average follow-up of 10 months (range of 8-12 months). Three
      patients had conjunctival erosion, which was well treated. All patients have
      cosmetically satisfactory motility of the prosthesis. CONCLUSION: Human umbilical
      cord tissue can be used as wrapping material of hydroxyapatite orbital implant.

PMID- 11593657
TI  - [Application of polyester fiber heart patches to secondary intraorbital
      implantation of hydroxyapatite spheres].
AB  - OBJECTIVE: To observe the effect of intraorbital implantation of hydroxyapatite
      spheres wrapped with polyester fiber heart patches. METHOD: According to the
      rectus contraction points four rectus were found and the rectus valves were
      created in anophthalmos. Then the hydroxyapatite sphere wrapped by the polyester
      fiber heart patch was inserted in the orbit. RESULT: There were 13 cases in this
      group. Of them 11 patients showed very good operative results, Local poor healing
      of bulbar conjunctiva and fascia occurred in 2 patients. The wound in one patient
      healed very well after a simple repairing operation and in the other the wound
      healed spontaneously without any special treatments. CONCLUSION: The effect of
      secondary intraorbital implantation of hydroxyapatite spheres wrapped by
      polyester fiber heart patches is positive. The polyester fiber heart patch is
      safe, reliable, cheap, very convenient in use and easy to obtain. It is a better
      substitute for sclera which is used to wrap the HA sphere.

PMID- 11593659
TI  - [Application of the scrotal axial skin flap in hypospadias repair].
AB  - OBJECTIVE: To present a new and reliable method for treatment of failed
      hypospadias repair. METHOD: The scrotal axial skin flap based on anterior scrotal
      vessels was designed and used in reconstruction of the urethra. 7 patients with
      failed hypospadias repair have been treated with this method since 1996. RESULT:
      There was no any complication in all the patients. CONCLUSION: The advantages of
      this method are that the flap has good blood supply and the potentiality of
      growth. It is suitable for treatment of hypospadias, especially the failed
      hypospadias repair.

PMID- 11593660
TI  - [Urethra fistula repair without using a urethral stent].
AB  - OBJECTIVE: To report the experience in fistula repair without a urethral stent.
      METHOD: During the operation, the wound after approximating the epithelium was
      made twice the diameter of the fistula. Then an adjacent flap was turned over to
      cover and close the fistula. 50 fistulae in 37 patients were repaired without
      using a urethral stent after the operation. RESULT: There has been no recurrence
      in the past 7 years. CONCLUSION: This method is one of the best ways for fistula
      repair and has a bright prospect in application.

PMID- 11593661
TI  - [The second dorsal metacarpal artery flap with distant pivot point].
AB  - OBJECTIVE: To introduce a modified flap pedicled with the second dorsal
      metacarpal artery. METHOD: Seven thumb wounds were repaired with the second
      dorsal metacarpal artery flap. The size of the flap ranged from 1 cm x 3 cm to 2
      cm x 4 cm, and the length of the vascular pedicle was 6 to 7 cm. RESULT: All
      flaps survived and the results were satisfactory. CONCLUSION: This method is an
      option for repairing thumb defects when the local skin flap or island flap on the
      index and middle finger is not available.

PMID- 11593662
TI  - [Cleft palate repair of infants with 32 cases].
AB  - OBJECTIVE: To search a proper time for cleft palate repair. METHODS: Thirty-two
      patients with unilateral and bilateral cleft palate, aged from 25 days to 3
      months, were undergoing the cleft palate repair. The surgical risk was analyzed
      perioperatively. The speech function and the maxillary development were also
      evaluated after the operation. RESULTS: All of the cases were successfully
      repaired with less bleeding, quicker recovery, shorter operative time and less
      psychological injury. The speech function and the maxillary development were very
      well. CONCLUSION: A patient, even under 3 months age, could also be a good
      candidates for cleft palate repairing when the general condition was good.

PMID- 11593663
TI  - [Precise determine the position of the opposite upper lid after correcting the
      congenital unilateral ptosis and their relationship].
AB  - OBJECTIVE: The good results should be obtained after correction of the congenital
      unilateral ptosis for bilateral eyes. METHODS: A formula was made and determined
      the position of the opposite upper lid according to Hering's law. RESULTS: Thirty
      two patients with congenital unilateral ptosis were operated. The correct rate is
      94.12% according to the formula and the control is 66.67%. CONCLUSION: The
      position of the opposite upper lid should be determined after the ptosis eye
      corrected before operation in order to obtain a good results.

PMID- 11593664
TI  - [Analysis of complications of augmentation mammaplasty in 12 patients].
AB  - OBJECTIVE: To reduce complications and to improve the long-term results of
      augmentation mammaplasty. METHOD: Twelve patients who had complications during a
      period of 1 to 13 years after augmentation mammaplasty were studied. The fibrous
      capsule of the breast implant was examined pathologically. RESULTS: 12 patients
      (15 breasts) were included in the study. Of the nine patients with unilateral
      augmentation mammaplasty, four had 1 complication; four had 2 complications and
      one had 3 complications. Of the three patients with bilateral augmentation
      mammaplasty, two had the same complication, one had 3 complications. Every
      complication has its pathologic and clinical characteristics. CONCLUSION: Many
      measures are important for reducing complications including strict surgical
      manipulation, proper selection of good implants, preferred submuscular insertion,
      whole capsulectomy for prosthesis rupture or leak and through hemostasis, proper
      bandage, massage and follow-up et al.

PMID- 11593665
TI  - [Inhibiting effect of antisense oligodeoxynucleotide of alpha 1(I) Precollagen
      gene on hypertrophic scar in an animal model].
AB  - OBJECTIVE: To study the effect of antisense oligodeoxynucleotide (ODN) of alpha
      1(I) precollagen gene on hypertrophic scar in an animal model. METHOD:
      Hypertrophic scar was explanted in athymic mice. The effect of antisense
      oligodeoxynucleotide 1 and 2 on the animal model and the inhibition of ODN1 and
      ODN2 were observed. RESULT: It was showed that antisense oligo (ODN1, 21 bp)
      located 5'end from the translation start region and antisense oligo (ODN2, 22 bp)
      between the first exon and the first intron could effectively inhibit scar
      hypertrophy. However the control groups showed no inhibition. CONCLUSION:
      Antisense oligodeoxynucleotide could effectively inhibit scar hypertrophy by
      inhibiting the synthesis of type I collagen protein.

PMID- 11593666
TI  - [The effects on melanoma and immunological mechanism of human interferon-alpha
      gene therapy by fibroblasts].
AB  - OBJECTIVE: To establish a model of fibroblast cell-mediated human IFN-alpha gene
      therapy for anti-melanoma. METHODS: BMGNeo-IFN-alpha DNA was transferred into
      NIH3T3 fibroblasts by the liposome method. The clone secreting the highest level
      of IFN-alpha was selected and implanted to mice intraperitoneally. RESULTS: From
      12 hours after implantation, IFN-alpha activity could be detected in serum of the
      animal and was sustained for a long time. We used the model to treat the nude
      mice inoculated with melanoma and found that the growth of M21 cells was
      inhibited obviously. CONCLUSIONS: The results demonstrated that fibroblasts could
      successfully transfer and express hIFN-alpha gene in vivo and the fibroblast cell
      mediated gene therapy could be used to treat human melanoma.

PMID- 11593667
TI  - [Anatomy in relation to posterior maxillary osteotomy].
AB  - OBJECTIVE: The most common site of haemorrhage in maxillary osteotomies is the
      posterior maxilla. Better understanding of the anatomy of this region would
      minimize possible vascular complications. The aim of this study is to investigate
      the anatomy of posterior maxilla and establish safety guidelines for Le Fort I
      osteotomy. METHOD: Thirty dry human skulls were selected for direct measurement
      and computerized image analysis. RESULTS: Synosteosis of the pterygomaxillary
      junction was noted in 10% of the samples. The height of the pterygomaxillary
      junction was 13.15 mm. The height from the inferior point of the pterygomaxillary
      junction to the inferior point of the maxillary tuberosity was 5.25 mm. The
      height from the superior point of the pterygomaxillary junction to the inferior
      point of the maxillary tuberrosity was 18.05 mm. The average distance from the
      piriform rim to the descending palatine canal was 35.25 mm. The width of the
      pterygoid process was 12.34 mm. The average length from the zygo-alveolar ridge
      to the pterygomaxillary junction was 25.47 mm. The average length from anterior
      nasal spine to the posterior nasal spine was 46.27 mm, and the angle between the
      descending palatine canal and the palate plane was 58 degrees 47'. CONCLUSIONS:
      The study is to provide further understanding of the posterior maxillary anatomy
      in relation to the bone-cut design of Le fort I osteotomy and to create clinical
      safety guidelines in order to avoid damaging the descending palatine vessels.

PMID- 11593668
TI  - [Current status of biomedical engineering].

PMID- 11593669
TI  - [Study of human tissue engineering cartilage].
AB  - OBJECTIVE: To investigate the technique of human tissue-engineered cartilage and
      to study the medical collagen membrane of guided tissue regeneration (GTR) as the
      carrier of in vitro chondrocytes culture. METHODS: Tissue engineering technique
      was used to make human Tissue-engineered cartilage, which was examined
      histologically and functionally. RESULTS: It was found that the chondrocytes
      seeded on the medical collagen membrane of GTR grew well. A layer of milk white
      and cartilage-like tissue grew on the surface of medical collagen membrane of GTR
      after 1 week. It was demonstrated that the cartilage-like tissue was strong
      enough to be transferred after being implanted for 8 weeks. The cartilage-like
      tissue was proved to be human tissue engineered cartilage by HE stain and Alcian
      blue-poncean S stain. The chondrocytes could secrete chondroitin sulfate as
      proved by Lev-Spicer stain. CONCLUSIONS: The medical collagen membrane of GTR has
      characteristics of three-dimensional structure and cell reticular function, and
      it has the possibility to be developed as a natural scaffold for tissue
      engineering. The results indicate that it is possible to make human tissue
      engineered cartilage with tissue-engineering technique.

PMID- 11593670
TI  - [Repair of rectovaginal fistula using pudendal-thigh flap pedicled on the
      obturator artery].
AB  - OBJECTIVE: This is to introduce a new method for repair of rectovaginal fistual.
      METHODS: On the basis of an anatomical study a new type of the pudendal-thigh
      flap pedicled on the obturator artery has been designed to repair rectovaginal
      fistual. RESULTS: 4 patients were treated with this method. All flaps survived
      and the fistula between vagina and rectum was closed primarily. CONCLUSIONS: The
      advantages of the pudendal-thigh flap pedicled on the obturator artery include:
      1. Good blood supply; 2. Relative thin and hairless; 3. Perfect hiding of the
      donor site. We think that it is one of the best methods of rectovaginal fistula
      repair.

PMID- 11593671
TI  - [One-stage vagina reconstruction using free flaps].
AB  - OBJECTIVE: To investigate the feasibility of vagina reconstruction using a free
      flap. METHODS: The dorsal pedal flap and the posterior leg flap have been used
      for vagina reconstruction in 25 cases. RESULTS: All of the operations were
      successful. Postoperative follow-up of the patients for 6 months to 6 years
      showed that the reconstructed vagina was satisfactory anatomically and
      physiologically. The vagina wall was not only pliable but also elastic. The
      married patients enjoyed their sexual life. Two of them have given birth to
      babies. CONCLUSIONS: Vagina reconstruction with a free flap as a new method can
      be performed successfully. The patients are happy with the operative results, as
      there is no scar left around the pudendum.

PMID- 11593672
TI  - [Combined treatment of pseudohermaphroditism].
AB  - OBJECTIVE: To diagnose and treat female pseudohermaphroditism caused by 21
      hydroxylase deficiencies. METHODS: Four female patients with 21-hydroxylase
      deficiencies have received combined treatment of reconstructive surgery and
      supplementary glucocorticoid in our hospital since 1990. RESULTS: The patients
      obtained a female external genitalia through the operation. Various symptoms
      resulted from 21-hydroxylase deficiency were improved with glucocorticoid
      therapy. CONCLUSION: A satisfying result can be achieved for
      pseudohermaphroditism by combination of surgery and medicine.

PMID- 11593673
TI  - [Applied anatomy of arterial supply for the soft palate].
AB  - OBJECTIVE: The correct design of a myomucosal or mucosal flap of the soft palate
      in the surgical procedure for cleft palate and velopharyngeal incompetence should
      be made with a thorough knowledge of the arterial supply for the soft palate,
      which is an important premise for functional rehabilitation of the soft palate
      postoperatively. METHODS: Anatomical dissection was undertaken in 14 cadavers (10
      normal adults, 2 normal newborns and 2 newborns with cleft lip & palate). The
      arteriography and histological studies have been used in 10 newborn and 6 aborted
      fetuses. RESULTS: The results showed that the arterial supply of the soft palate
      is multi-original and the principal artery is the ascending palatal artery. Its
      anterior and posterior branches are myomucosal perforators. The other vessels to
      supply the soft palate are direct mucosal branches, which include the lesser
      palatine artery, the palatal branch of the ascending pharyngeal artery and the
      tonsillar artery. All above arteries anastomose under the mucosal, muscular and
      fascial layers in the soft palate. In cleft cases, all arteries in the soft
      palate are displaced anterior-laterally because of the deformities of the palatal
      muscles and bone structure. CONCLUSIONS: This study supports the facts that the
      major blood supply of the soft palate comes from ascending palatine artery and
      the generous arterial anastomosis of the velum allows it to tolerate the proper
      dissection during palatoplasty. We believe that decreasing the damage of the
      intrapalatal vascular supply by carefully dissection around the hamulus is very
      important to prevent wound break down, muscular fibrosis, flap failure, and also
      is the basis of design for surgical procedure and postoperative functional
      recovery in cleft palate patients.

PMID- 11593674
TI  - [The superficial vein, cutaneous nerve and its nutrient vessels in the forearm:
      anatomic study and the clinical implication].
AB  - OBJECTIVE: To provide an anatomic basis for designing the flap pedicled with
      neurocutaneous nutrient vessels, and for further understanding of this flap and
      its relations with other local venous flaps. METHODS: Microanatomy and red-and
      blue latex injection transparency method were applied to study 1. The medial
      antebrachial cutaneous nerve (MACN), the lateral antebrachial cutaneous nerve
      (LACN) and their nutrient vessels; 2. The relationship between the basilic vein
      and MACN and its nutrient vessels; and 3. The relationship between the cephalic
      vein and LACN and its nutrient vessels. RESULTS: MACN is vascularized by
      paraneural vessels and LACN is by both paraneural vessels and the long artery.
      MACN is accompanied by its paraneural vessels and the basilic vein, so do LACN by
      its nutrient vessels and the cephalic vein. The distance range from the cutaneous
      nerve to its accompanying superficial vein is less than 1 cm, to its paraneural
      vessels is less than 0.4 cm; and the distance range from the paraneural vessel to
      the superficial vein is about 0.3-1.2 cm. CONCLUSIONS: A flap pedicled with
      cutaneous nutrient vessels could be designed along a superficial vein. The type
      of flap might be different because of the different neurocutaneous blood supply.
      Some locally transferred venous flap might be a flap pedicled with neurocutaneous
      nutrient vessels.

PMID- 11593675
TI  - [The orthognathic treatment of developmental mandibular asymmetry].
AB  - OBJECTIVE: To explore the methods of orthognathic treatment for the developmental
      mandibular asymmetry to simultaneously achieve satisfactory facial appearance and
      oral functions and to prevent recurrence of the deformity. METHODS: 37 cases of
      developmental mandibular asymmetry have been treated in past seven years. The
      type of the deformity, the management of the cases, and the effects of therapy
      were summarized in this paper. RESULTS: According to the type of the asymmetric
      deformity, different means were used. After treatment, all the patients obtained
      satisfactory facial appearance and oral function. CONCLUSIONS: During the
      orthognathic treatment, it is important to simultaneously ameliorate facial
      appearance and achieve good oral function. It should be diagnosed before surgery
      whether the development of the deformity is steady or not. The correction of
      skeleton and soft tissues must be performed by stages.

PMID- 11593676
TI  - [Total nose reconstruction with a reversed mandibular flap pedicled with the
      facial artery].
AB  - OBJECTIVE: To investigate the method to repair different kinds of nasal defects.
      METHODS: The reversed mandibular flap pedicled with the facial artery was used.
      RESULTS: The treatment was completed in one stage and the results were
      satisfactory in 6 cases. The reconstructed noses showed good shape. CONCLUSIONS:
      Total nose reconstruction using a reversed mandibular flap is a new operation
      design and technique. The recipient and the donor sites are very close. The flap
      with excellent blood supply has a good colour and textural match. The operative
      procedure and flap transferring are easy.

PMID- 11593677
TI  - [Skin sparing incision mastectomy and immediate TRAM flap breast reconstruction].
AB  - OBJECTIVE: In order to achieve a high-quality reconstructed breast, we improved
      the operation method using the skin sparing incision mastectomy and immediate
      TRAM flap breast reconstruction. METHODS: Patients with duct carcinoma in situ
      were selected to undergo mastectomy with a skin sparing incision. The site of the
      previous biopsy incision was marked around the areola, and then the preferred
      skin sparing incision included the nipple-areola complex and a margin around the
      biopsy site for the non-ptotic breast. The excised skin was replaced as precisely
      as possible with the TRAM flap skin immediately. While the mastectomy was being
      performed the TRAM flap was incised and elevated. The pedicled or free TRAM flap
      has been used for 34 patients. Nipple-areola reconstruction was made at the
      second stage. RESULTS: The results of the skin sparing breast reconstruction are
      better than other breast reconstruction techniques in the breast's shape, colour,
      sensation, symmetry and incision scar. CONCLUSIONS: Skin sparing incision
      mastectomy with immediate TRAM flap breast reconstruction technique is an ideal
      breast reconstructive method for the patients with breast duct carcinoma in situ.
      The advantages of the method include 1. The TRAM flap is an autograft without
      rejection; 2. The reconstructed breast has good shape and better sensation than
      other autograft reconstructive techniques since most breast skin has been spared;
      3. The symmetry of the reconstructed breast with the contralateral breast is
      improved.

PMID- 11593678
TI  - [Clinical application of the first metacarpal fasciocutaneous flap].
AB  - OBJECTIVE: To report the application of the first metacarpal fasciocutaneous flap
      in repairing digital soft tissue defects. METHODS: The first metacarpal
      fasciocutaneous flap was designed to repair the lesions of the thumb, index,
      middle and ring fingers in 14 cases. The blood supply of the flap originates from
      the branches of the radial pollicis artery at the metacarpophalangeal joint and
      the venous drainage is to the cephalic vein through the deep pollicis vein and
      dorsal pollicis vein. RESULTS: All the flaps survived successfully except that
      one survived partly, two had cyanosis and blister. Followed-up for 3 to 12 months
      showed the flaps had sensation with good texture and thickness. CONCLUSIONS: The
      first metacarpal fasciocutaneous flap can be used to repair the lesions of the
      thumb, index, middle and ring fingers. It has following advantages: 1. reliable
      blood supply; 2. convenient dissection and 3. less damage of the donor site.

PMID- 11593679
TI  - [The experimental study on acute and chronic expansion of the facial nerve].
AB  - OBJECTIVE: To investigate and compare the feasibility of acute and chronic
      expansion of the facial nerve so as to provide referable parameters for clinical
      practice. METHODS: Buccal branches of rabbits' facial nerve were expanded with
      the expander designed and manufactured by us. The nerve was elongated 10 mm per
      10 min in the acute group, and 1.5-2.0 mm per day in the chronic group. The nerve
      injury due to expansion, the nerve retraction after expansion and the limit of
      elongation were investigated. When the expansion was completed, 1.0 cm segments
      of the nerve in both acute and chronic groups were removed and epineurium
      neurorrhaphy was performed. The same length of the nerve in the control group was
      resected and replanted. Electromyogram(EMG) and nerve conductive velocity (NCV)
      were measured at the 15th week of expansion to assess the function of the
      repaired nerve. The pathological changes were also observed. RESULTS: 1. The
      nerve retracted obviously during the first hour after expansion. The difference
      were significant between the acute group (37.6 +/- 4.5)% and the chronic group
      (8.2 +/- 2.1)%. 2. Excluding the retraction portion, the limit elongation was
      (18.7 +/- 2.4)% and (31.8 +/- 2.4)% in acute and chronic group respectively. 3.
      To get the same elongation within the limit, nerve injury was more severe
      pathologically in the acute group than in the chronic one at the end of the
      expansion while EMG and NCV were not different considerably. 4. Within the limit
      elongation, the same result of neurorrhaphy was gained in the acute, chronic and
      the control groups. CONCLUSIONS: Acute expansion of the facial nerve is feasible.
      When the defect is less than 20% of the nerve, acute expansion is indicated. When
      it is over 20% but less than 30%, a chronic method should be taken into
      consideration. The same outcome of repair should be gained if the expansion is
      within the limit elongation.

PMID- 11593680
TI  - [Histochemical study and classification of facial muscles fibers].
AB  - OBJECTIVE: To study the histological and histochemical characteristics of the
      facial muscle fiber. METHODS: Seven biopsy specimens of the facial muscle from
      twelve patients were stained with histochemical method. The diameter and the
      histochemical type of the fibers were analysed by staining of M-ATP ase and NADA
      TR. Type I and type II fibers were evaluated respectively by means of computer
      assisted image analysis. RESULTS: The fiber diameter is between 24.3-63.9
      microns. According to the quantity of fiber I, facial muscles may be classified
      into three groups: 1. Phasic muscle contains less than 20 percent of type I
      fibers; 2. Intermediate muscle contains 21 to 40 percent of type I fibers; 3.
      Tonic muscle contains 41 to 69 percent of type I fibers. CONCLUSION: The results
      of the study show that the histological and histochemical difference of facial
      muscles may have significance in facial paralysis restoration.

PMID- 11593681
TI  - [Study on type I and type III procollagen mRNA and in situ collagen proteins
      expressions in hypertrophic scars after intralesional Kenalog treatment].
AB  - OBJECTIVE: This is to investigate the mechanism of effects of Kenalog on type I
      and III collagen syntheses and degradation in hypertrophic scars. METHODS:
      Intralesional injection of Kenalog was performed on 6 patients with hypertrophic
      scars. On the 3rd day and 7th day after the treatment, 6 samples from the 6
      patients each were collected and type I and III collagen proteins and in situ
      procollagen mRNA expressions were studied by means of immunohistochemistry and
      molecular biology. RESULTS: On the 7th day after intralesional injection of
      Kenalog, type I collagen proteins reduced (P < 0.05) and type III collagen
      proteins did not reduced significantly (P > 0.05). On the 3rd day after
      intralesional injection of Kenalog, both type I and type III procollagen mRNA
      expressions were significantly inhibited and on the 7th day both procollagen mRNA
      expressions decreased further. CONCLUSIONS: Intralesional Kenalog may inhibit
      type I procollagen mRNA expression more than type III. Gene expressive intensions
      of type I and III procollagen were higher in hypertrophic scars than in normal
      skin.

PMID- 11593682
TI  - [Progress in the study of tissue engineering of bone and cartilage].

PMID- 11593683
TI  - [Removing excess fat in plastic surgery].

PMID- 11593685
TI  - [Surgical resection of giant hemangioma].
AB  - OBJECTIVE: Through the operative experiences in 45 cases of giant hemangioma, it
      is elucidated that the operative procedure for hemangioma is an effective,
      radical method of treatment. METHODS: 1. Preoperative DSA can establish the
      diagnosis, delineate the range of lesion and facilitate the design of operation.
      2. "Dissection over the false capsule" is applied in the operation. 3. The
      operative wound, is repaired with a plastic procedure. RESULTS: Of the 45
      patients primary cure was obtained in 27, and secondary cure in 13 with effective
      rate of 89 percent. The followed-up was as long as 8 years with excellent
      results. CONCLUSIONS: The establishment of operative scheme is chiefly based on
      preoperative DSA, and the success is fundamentally determined by complete
      dissection over the so-called "false capsule" around the tumour during operation.
      This procedure can totally remove the tumour, eliminate recurrence and fulfil the
      purpose of radical resection, which is worthy of wide application.

PMID- 11593684
TI  - [Inner-hemangioma ligation and pingyangmycin injection in hemangioma (with 30
      cases report)].
AB  - OBJECTIVE: To provide a simple and safe surgical approach in treating cavernous
      and racemose hemangioma. METHODS: First cross-ligate the hemangioma, as to divide
      the tumor into independent compartments, them inject pingyangmycin into the
      compartments respectively. RESULTS: There are 30 cases in this group (35
      hemangiomas). Twenty-four cases (28 hemangiomas) were totally cured, accounting
      for 80%; Six cases were improved (7 hemangiomas) for 20%; There was no
      ineffective case. CONCLUSION: "Inner-hemangioma ligation and injection of
      pingyangmycin" has broad surgical indications, with desirable outcome in treating
      cavernous and racemose hemangioma, especially those unsuitable for surgery, or
      ineffective simply by inner-hemangioma injection.

PMID- 11593686
TI  - [Ehancement of tissue expansion in guinea pig by local delivery of chemical
      agents using a new type expander].
AB  - OBJECTIVE: To search for the new method to increase the rate of tissue expansion.
      METHODS: A new type of double-lumen expander was buried in the back of guinea
      pig. Through the expander chemical agents (papaverine) were delivered. RESULTS:
      The new expander could effectively deliver chemical agents. In comparison with
      the control group, the blood flow, survival length and the length to width ratio
      of the expanded flap in the experimental group increased statistically. The
      immediate retraction ratio of the flap decreased significantly. The epidermis was
      thicker while the dermis was not significant different from the control. The
      panniculus carnosus was significant thinner in the expanded group than the
      unexpanded group. The deep connective tissue was statistically thinner in the
      group using the new type expander. CONCLUSION: The new type of expansion method
      could accelerate tissue expansion rate and improve the quality of expanded skin
      and flap.

PMID- 11593687
TI  - [Experiment research on the mechanism of skin contracture after expansion].
AB  - OBJECTIVE: The aim of this study is to observe the repairing process of skin
      chronic injury due to expansion and explore the mechanism of skin contracture
      after expansion. METHODS: 20 dogs used in this study were divided randomly into
      four groups. Skin samples were collected from the back of dogs when expansion
      finished and 3 months, 6 months, 1 year after expansion. Normal skim from the
      other side on the back of dogs was used as control group. The dermal
      ultrastructure was observed by electriscope. The expression of alpha-SMA in
      dermis at different stage has been analyzed by immunohistochemistry, and the
      concentration of intracellular free Ca2+ in the fibroblast has been measured by
      Fura-2 fluorescen indicator. Meanwhile we constructed a 3-dimension system in
      vitro to analyze the afgfect of different cell density and collagen concentration
      to fibroblast contracture. RESULTS: (1) The microfilment in fibroblast was
      fragile, and the features of myofibroblast was absent, the collagen fibers were
      returned to reticular arrangement along with time. One after expansion few of the
      collagen remained irregular in arrangement and aparse. (2) After expansion the
      concentration of Ca2+ increased significantly. (3) In 3-D culture system the
      density of fibroblasts positively corresponded to fibroblast contracture and the
      collagen concentration negatively corresponded to it. CONCLUSION: After expansion
      the dog skin has a structure between scar tissue and thoroughly regeneration
      skin. Dermal fibroblast is the dynamic source of the skin contracture, meanwhile
      the density of fibroblast and collagen concentration are two essential factors
      during skin contracture.

PMID- 11593688
TI  - [Analyzing study of complications of tissue expansion related to the injectable
      system].
AB  - OBJECTIVE: To analyze the complications of tissue expansion related to its
      injectable system. METHODS: One hundred and ninety six patients were followed up
      and analyzed for the complications of the tissue expansion concerned to its
      injectable system. The management of these complications was also reviewed.
      RESULTS: There were five kinds of the complications(with the occurrence of 32%)
      related to the injectable system in this group patients. The highest frequency of
      the complications occurred in the implantation stage. Further management was also
      documented well. CONCLUSION: The complications of tissue expansion related to the
      injectable system occurred commonly and should be paid more attention on them.

PMID- 11593689
TI  - [Maintenance of foot sensory function by end-to-side neurorrhaphy].
AB  - OBJECTIVE: The purpose of this paper is to introduce the experience in
      maintaining or reconstructing foot sensory function after harvesting skin flap
      from the leg. METHODS: After dissecting the fasciacutaneous flap in the medial
      leg, the end-to-side neurorrhaphy was performed between the distal saphenous
      nerve and the sural nerve. When the retrograde-flow neurocutaneous island flap
      was raised, the end-to-side neurorrhaphy was carried out between the sural nerve
      carried by the flap and the cutaneous nerve of the foot dorsum. Also a less
      important cutaneous nerve branch can be harvested and implanted into the
      denervated flap in the foot with the other end of the nerve sutured to the
      lateral side of the cutaneous nerve of the foot dorsum. RESULTS: This operation
      was performed on three patients. Postoperative follow-up of 9 to 36 months
      revealed good results. CONCLUSION: This technique is simple and effective.

PMID- 11593690
TI  - [Anatomical study and clinical application of a leg flap pedicle-included with
      cutaneous nerve and its concomitant vessels].
AB  - OBJECTIVE: To investigate the blood supply patterns and the clinical liability of
      a leg flap pedicle-included with cutaneous nerve and its concomitant vessels.
      METHODS: Fresh cadaver legs with thirty-two in infants and two in adults were
      anatomically examined after the intravenous injection of the red Chlorinated Poly
      Vingl Choride (CPVC). Five patients with the soft tissue defects were selected
      for the treatment with the flap pedicle-included with the cutaneous nerve and its
      concomitant vessels. RESULTS: Four main cutaneous nerves were found in the leg
      after they perforated the deep fascia out. They were companioned with their
      concomitant vessels with different blood-supply pateeerns, which the upper part
      of the leg was in an axial pattern and the lower part was in a "chain-type
      anastomosing" pattern. Following the above-mentioned findings, five cases were
      successfully treated with this led flap. CONCLUSIONS: The leg flap should be
      designed along the cutaneous nerve and its concomitant vessels. When the flap is
      applied in the area of blood supply with "chain-type anastomosing" pattern, the
      deep fascia should also be included in the flap.

PMID- 11593691
TI  - [Reconstructing the limb end defects with a free mini-flap, a report of 18
      cases].
AB  - OBJECTIVE: Some operative procedures were introduced for repairing hand or foot
      defects using the free mini-flap from the finger or toe. METHODS: Eighteen cases
      of finger tip or foot wound were treated with the free mini-flap and vessel
      anastomosis. The size of the flap was 2 cm x 1 cm to 6 cm x 4 cm and the length
      of the pedicle was 2 to 4 cm. RESULTS: All the eighteen free mini-flaps survived
      and the results were satisfactory. CONCLUSION: The method of the mini-flap is a
      good option for covering of thumb, finger or foot defects when a local or an
      island flap is not available.

PMID- 11593692
TI  - [Correlation between endothelin, nitric oxide and microcirculation in super
      thinned skin flap in pig].
AB  - OBJECTIVE: To investigate the influence of the endothelin (ET) and the nitric
      oxide (NO) on the microcirculation of a super-thinned skin flap. METHODS: With
      pig, a super-thinned skin flap, only including subdermal vascular networks, was
      raised and sutured back on its bed on one flank of each pig, and on the other
      flank a traditional skin flap was also formed for the controlled group. A laser
      Doppler Flowmeter was used for evaluation of the blood circulation before and
      after the operation. The endothelin and the nitric oxide of the flap were
      examined after certain times of the operation. Furthermore, the necrosis of each
      flap was decided 7 days after the operation. RESULTS: The ET and NO were
      significantly increasing after 1 hour of the operation in both of the groups (the
      peak value of ET at 6 hours and NO at 3 hours after the operation). However, the
      ET in the super-thinned flap group was significantly lower at 1, 3, 6 hours after
      the operation, compared with the centrolled group (P < 0.05), but the NO measured
      meantime was significantly higher than the control (P < 0.05). The blood flow of
      the super-thinned flap was significantly higher than the control flap separately
      at 1, 3, 6 hours after the operation (P < 0.01). The survival of the super
      thinned flap increased about 35% more than the control. There was a negative
      correlation existed between the ET and the blood flow, as well as a positive
      correlation between the NO and the blood flow. CONCLUSION: This study has
      indicated that the changes of the ET and NO in the flaps, especially in the super
      thinned flap, have strongly correlated with their microcirculation. The highter
      survival rate of the super-thinned flap might owes to the mechanism which the ET
      in the flap produces less while the NO more, Compared with the traditional skin
      flap.

PMID- 11593693
TI  - [Experimental study on revascularization of subdermal vascular network thin
      flap].
AB  - OBJECTIVE: To investigate the survival mechanism of subdermal vascular network
      thin flap (SVNF). METHODS: 24 rabbits were divided into three groups, in which
      the SVNF, subdermal vascular network skin graft and the traditional random flap
      were created respectively. Tissue hyalinization technique was used to find out
      the differences of vascular architecture between the three groups at the 1st-7th
      day, and the 14th day postoperatively. RESULTS: The results showed that the blood
      supply reestablished earlier in SVNF group than the other two groups. CONCLUSION:
      There is a zone of rapid and intensive angiogenesis in the mid-part of SVNF known
      as "intermediary pedicle". This is the anatomic basis of the early pedicle
      division and superior survival ratio of SVNF.

PMID- 11593694
TI  - [Autogenous costochondral graft applied in the reconstruction of the
      temporomandibular joint].
AB  - OBJECTIVE: To study the surgical treatment of ankylosis of the temporomandibular
      joint. METHODS: Autogenous costochondral grafts were applied in the
      reconstruction of the temporomandibular joint in 27 cases with condyle ankylosis
      from 1988-1998. The follow up period was 1-10 years. The pre- and post-operative
      degree of mouth opening and the TMJ function was examined. RESULTS: Postoperative
      mouth opening was improved up to 2 cm in the 27 cases. All the results were
      successful without recrudescence of condyle ankylosis. CONCLUSION: The use of
      autogenous costochondral grafts in TMJ reconstruction is the best method in the
      treatment of TMJ ankylosis.

PMID- 11593695
TI  - [The diagnosis and treatment of microgenia].
AB  - OBJECTIVE: This article is to elucidate the indications of horizontal advancement
      osteotomy of the mandible or bone grafting for microgenia. METHODS: After
      understanding the characteristics of a patient's inferior one-third facial
      malformation through physical and cephalometric measurement, we correct the
      malformation of moderate or serious degree with osteotomy genioplasty. RESULTS:
      Eight patients received the operation and obtained good results. CONCLUSION:
      Understanding the characteristics of microgenia and choosing a rational method is
      the prerequisite for a good operative result.

PMID- 11593696
TI  - [Repair of soft tissue defect of the hand with a fascia lata flap by
      microvascular anastomosis].
AB  - OBJECTIVE: This is to report the clinical experience in repair of the soft tissue
      defects of the hand using a free fascia lata flap and skin graft. METHODS: Eight
      cases of soft tissue defects of the hand were repaired with a fascia lata flap by
      means of microvascular anastomosis. The size of the fascia lata flap ranged from
      2.5 cm x 7 cm to 6 cm x 16 cm. RESULTS: All the fascia lata flaps survived
      completely with satisfactory results. CONCLUSION: The flap is nourished by the
      descending branch of the lateral femoral circumflex artery and seems to have a
      constant vascular supply and a long pedicle. The dissection of the flap is easy.
      The flap is thin and very suitable for repair of soft tissue defects of the hand.

PMID- 11593697
TI  - [Lower lid blepharoplasty by using the principles of plastic surgery and the
      technique of orbital fat release].
AB  - OBJECTIVE: To create a new method for lower lid blepharoplasty in order to
      prevent the complication of lower lid ectropion after the operation. METHODS:
      Eight patients with 16 eyelids were undergoing the lower lid blepharoplasty with
      the use of plastic surgery principles and the technique of orbital fat release.
      The following-ups were carried out in each patient. RESULTS: Eight patients with
      16 eyelids were treated with the above-mentioned technique. The satisfactory
      results were achieved with good appearance. CONCLUSION: The above-mentioned
      technique is a safe, simple and effective method for the lower lid
      blepharoplasty.

PMID- 11593698
TI  - [The effects of beta-aminopropionitrile on the proliferation in cultrured human
      hypertrophic scar fibroblasts].
AB  - OBJECTIVE: To observe the effects of BAPN on the proliferation in cultured human
      hypertrophic scar fibroblasts. METHODS: By means of colorimetric MTT(tetrazolium)
      assay and flow cytometry, we tried to find the effects of BAPN with different
      concentrations and different time on the proliferation in cultured human
      hypertrophic scar fibroblasts. RESULTS: Concentrations of BAPN 0.074, 0.222,
      0.667, 2.0, 6.0 mg/ml could inhibit proliferation in cultured human hypertrophic
      scar fibroblasts, but had no effects on cultured human normal dermal fibroblasts.
      Its ID50 is 2.53 mg/ml. CONCLUSIONS: BAPN could inhibit proliferation in cultured
      human hypertrophic scar fibroblasts and was dependent on concentration and time.

PMID- 11593699
TI  - [The expression level of the transfected hEGF gene to cultured human epidermal
      cells].
AB  - OBJECTIVE: To study the stable expression levels of cultured human epidermal
      cells transfected with a hEGF-plasmid. METHODS: The 60%-70% confluent cultured
      human epidermal cells were transfected with a pBK-Signal-EGF plasmid-construct
      mediated by lipofectAMINE. After screening of G418 successfully transfected,
      clone forming cells were picked and subcultured for several weeks. To detect hEGF
      expression levels and to determine long term transgenic stability a specific
      ELISA was used. RESULTS: (1) hEGF plasmid constructs were successfully introduced
      into cultured human epidermal cells. (2) Transgenic expression still persisted
      after four subcultures. (3) hEGF expression levels could be detected in the
      medium over a six-week period. CONCLUSIONS: The stable expression of hEGF was
      obtained after gene transfected with the pBK-Signal-EGF plasmid mediated by
      lipofectAMINE.

PMID- 11593700
TI  - [Cosmetic surgery of cheek and anatomy buccal fat pad].

PMID- 11593701
TI  - [Laparoscopic radical prostatectomy--initial 10 cases].
AB  - PURPOSE: We report the clinical results and efficacy of laparoscopic radical
      prostatectomy for localized prostate cancer. PATIENTS AND METHODS: Between
      December, 1999 and June, 2000 we performed transperitoneal laparoscopic radial
      prostatectomy on 10 patients with T1 or T2 organ confined prostate cancer
      according to the techniques as described by Guillonneau et al. Different points
      were as follows: 1) We placed double J catheters during surgery to prevent
      ureteral injury. 2) We treated dorsal vein complex using an Endo-GIA-stapler. 3)
      We dissected the bladder neck from the prostate using an ultrasound scalpel in
      the manner to preserve the bladder neck. RESULT: We could not completed
      laparoscopic prostatectomy on two patients because of massive bleeding from
      dorsal vein and consuming too much time to suture urethra-bladder anastomosis.
      The average operating time in all cases was 8.1 hours including 1.8 hours in
      laparoscopic pelvic lymphadenectomy. The average estimated blood loss in all
      cases was 859 ml. There were 2 surgical complications with bladder injury and
      port site hernia. The histological examination revealed prostate cancer; pT2pNO
      in 8, pT3pNO in 2. The surgical margin and lymph nodes were negative in all
      patients. The duration of an indwelling catheter ranged from 5 to 40 days mean 17
      days. The duration to recovery of normal micturition was 6 to 90 days, mean 40
      days. CONCLUSION: Long-term follow-up and extensive studies are necessary to
      evaluate the efficacy of this procedure. It might provide shorter duration of an
      indwelling catheter and earlier recovery of normal micturition as compared with
      the conventional open surgery.

PMID- 11593703
TI  - [Outcome of neonates born with unilateral multicystic dysplastic kidneys].
AB  - AIMS: To review our experience of neonates with unilateral multicystic dysplastic
      kidneys (MCDKs) and to plan how to manage this anomaly. PATIENTS AND METHODS:
      Forty-eight neonates (30 boys, 18 girls) with unilateral MCDK were referred to
      our institute between August 1991 and February 1999. Urological evaluation was
      performed by USG, VCUG and radionuclide study. Follow-up period was 15 month to
      106 months (Ave. 54 months). RESULTS: Forty-five of 48 (93.8%) MCDKs were found
      prenatally. No surgical procedure was performed in utero. Seven (14.6%) had low
      grade vesicoureteral reflux (ipsilateral 5, contralateral 2). Dilation of
      contralateral upper urinaly tract was detected in 16 (33.3%) neonates and
      diuretic renography revealed 4PUJ obstruction and 2 mid-ureteral stenosis.
      Although 29 of 48 (60.4%) MCDKs were large, no neonate showed mass effect which
      caused vomiting or dyspnea. All MCDKs except two, which removed because of
      ipsilateral ureterocele or ectopic ureter, were followed conservatively. Two boys
      had nephrectomy when they became 5-year-old on their parent's request. Surgical
      correction of contralateral urinary tract anomaly, 3 pyeloplasty and 2 end-to-end
      ureteral anastomosis, was performed. All neonates but one with contralateral
      hypodysplastic kidney had good renal function. Neither hypertension nor malignant
      tumor had occurred. CONCLUSION: These findings suggest that neonates with
      unilateral MCDKs can be treated conservatively only if they have no contralateral
      serious anomaly. Surgical intervention is not necessary for unilateral MCDKs
      before and after birth but socially and/or economically it depends on patients'
      request.

PMID- 11593702
TI  - [Retrospective evaluation of PSA density for selection of biopsy candidates with
      prostate specific antigen in the gray zone].
AB  - PURPOSE: We examined the usefulness of prostate specific antigen density (PSAD)
      for selection of biopsy candidate with prostate specific antigen levels between
      4.1 and 10.0 ng./ml. in prostate cancer screening retrospectively. MATERIALS AND
      METHODS: The screening was conducted on male candidates in Natori city, aged 55
      years or older, for 6 years from 1994 through 1999. We could analyze serum PSA
      levels and PSA density in 118 men with PSA levels between 4.1 and 10.0 ng./ml.
      All of 118 men underwent ultrasound guided systematic prostate biopsy regardless
      of findings of digital rectal examination and transrectal ultrasound. Prostate
      volume was estimated by transrectal ultrasound measurements using the prolate
      ellipse formula (pi/6 x length x width x height). PSAD was calculated by dividing
      serum PSA level by prostate volume. Serum PSA levels were determined by Tandem-R
      assay. RESULTS: In 118 men, twenty-five men had prostate cancer. There was no
      significant difference in mean PSA between those with prostate cancer and those
      without prostate cancer, but the difference was significant in the mean PSA
      density (mean 0.26 and 0.16, respectively, p < 0.0001). Receiver operating
      characteristic curves for PSA and PSAD demonstrated superior benefit for PSAD in
      118 men. A sensitivity, a specificity, a positive predictive value and a negative
      predictive value of PSAD cut-off of 0.15 were 88%, 52.7%, 33.3% and 94.2%. PSAD
      cut-off of 0.18 showed the highest sum of sensitivity and specificity, which gave
      a sensitivity of 80%, a specificity of 72%, a positive predictive value of 43.5%
      and a negative predictive value of 93.1%. PSAD cut-off of 0.15 would seem to be
      preferable to cut-off of 0.18 because of less cancer missing. CONCLUSIONS:
      Although further studies are needed to determine optimal cut-off value to be used
      in clinical practice, PASD seems to be useful for the selection of biopsy
      candidates with PSA levels of 4.1 to 10.0 ng./ml. in the prostate cancer
      screening.

PMID- 11593704
TI  - [Treatment of phimosis with betamethasone ointment in children].
AB  - OBJECTIVE: We evaluated the efficacy of betamethasone ointment in the treatment
      of childhood phimosis and determined the most effective concentration of
      betamethasone. MATERIAL AND METHODS: Between August 1996 and May 2000, 69
      patients (median age 3.0, range 0-12) presented to our department with severe
      phimosis (grade 4, Tsugaya's classification), and were enrolled in this study and
      treated with betamethasone ointment for 4 weeks. The ointment was applied on the
      narrowed preputial skin twice a day by parents. During the first week, parents
      were asked not to retract the foreskin. After this period, parents were
      encouraged to retract the foreskin gently and without intense tension. The
      concentration of betamethasone were 0.12%, 0.05% and 0.025%. If the patients
      become to be able to retract foreskin satisfactory, we consider the state as
      complete response. If he become to be able to retract to allow partial exposure
      of the glans, we consider the state as partial response. We compared the efficacy
      among each of the concentrations, and at 3 months after the end of the treatment,
      we also assessed the adverse effects and recurrence. RESULTS: The overall success
      rate was 85.5%. Success rates with 0.12%, 0.05% and 0.025% ointment were 96.8%,
      82.8% and 55.6%, respectively (p = 0.0001). The 0.12% ointment was most
      effective. Recurrence was observed in 3 patients (4.3%). No adverse effects were
      observed in any of the patients. CONCLUSIONS: Treatment with betamethasone
      ointment is very effective, easy and safe. We recommend betamethasone ointment as
      the first treatment of choice for childhood phimosis.

PMID- 11593705
TI  - [A case of gastrointestinal stromal tumor of rectum, difficult to differentiate
      from leiomyosarcoma of prostate].
AB  - A 70 year-old male was seen at the hospital with the chief complaints of frequent
      miction and incomplete urinary retention. A hen's egg-sized firm mass was
      palpable in anterior wall of rectum by digital rectal examination. Intravenous
      urography showed severe bilateral hydronephroureter. Transrectal ultrasound, CT
      scan and MRI revealed a mass with 5 cm in diameter between prostate and rectum,
      and the margin of them were unclear. On needle biopsy of the tumor,
      leiomyosarcoma of the prostate was suspected. We performed radical cytectomy and
      created continent urinary reserver. Because the tumor and rectum could not be
      lysed, part of the rectum was resected. Histological examination showed
      gastrointestinal stromal tumor (GIST) of rectum. GIST of rectum is a rare entity,
      and in case of contact with the prostate, it is difficult to differentiate from
      leiomyosarcoma of prostate.

PMID- 11593706
TI  - [Penile skin metastasis of gastric carcinoma associated with prostate carcinoma:
      a case report].
AB  - Skin metastasis of internal carcinoma is a rare situation and its risk is
      reported as 0.7-9%. The site of skin metastasis is more popular at upper part of
      the body such as neck and face. We report a case of perineal and penile skin
      metastases of gastric carcinoma associated with prostatic carcinoma. A 72-year
      old man, who underwent total gastrectomy for gastric carcinoma 4 years ago, was
      found to have sclerotic change at perineal and penile skin. As his serum PSA
      level was 10.6 ng/ml, transrectal prostate biopsy and penile skin biopsy were
      performed. The prostate tissue pathologically demonstrated moderately
      differentiated adenocarcinoma and it was positive for both anti-PSA and anti-CEA
      antibody by immunohistochemical staining. The skin tissue was found to be
      infiltrative adenocarcinoma, negative for PSA and positive for CEA, which was
      compatible with the primary gastric carcinoma specimen. The patient had been
      treated for 7 months with administration of Doxifluridine and injection of LH-RH
      agonist, but died for progression of gastric carcinoma. A risk of skin metastasis
      of gastric carcinoma is reported as 6%, however, its metastasis to perineal and
      penile skin is the first case reported in the literature.

PMID- 11593707
TI  - [A case of adult neuroblastoma arising in the retroperitoneal space].
AB  - Neuroblastoma, common in children, rarely develops in adults. We recently treated
      a patient with adult neuroblastoma. A 34-year-old man complained of a swelling in
      right inguinal region. CT scan showed swelling of retroperitoneal and inguinal
      lymph nodes, and bone scintigram by 99mTc-HMDP showed an abnormal uptake in the
      swollen lymph nodes. Chemotherapy with CDDP (cisplatinum), VP-16 (etoposide), BLM
      (bleomycin), ADM (adriamycin) was not effective. Histopathological examination of
      a biopsy specimen revealed neuroblastoma. Another chemotherapy with CPM
      (cyclophosphamide), VCR (vincristine), ADM, DTIC (dacarbazine), CDDP, VP-16 was
      effective in decreasing the tumor size. Further high dose chemotherapy with CPM,
      ADM, CDDP, VP-16 combined with peripheral blood stem cell transplantation led to
      almost complete disappearance of the tumor and normalization of blood tumor
      markers (neuron specific enolase and immunosuppressive acidic protein).
      Retroperitoneal lymph node dissection demonstrated well-differentiated
      neuroblastoma in the excised tissue. Six months postoperatively, the tumor
      recurred in the pelvic cavity. Although chemotherapy and radiotherapy were given,
      he died of the disease 12 months postoperatively.

PMID- 11593708
TI  - [Laparoscopic extraperitoneal bladder diverticulectomy: an initial case report].
AB  - We report a case with a large bladder diverticulum caused by the bladder outlet
      obstruction, which was successfully treated with laparoscopic extraperitoneal
      diverticulectomy. The patient was a 71-year-old man, who had had dysuria,
      micturition pain and cloudy urine. We found the patient to have benign prostatic
      hyperplasia and a large diverticulum of the bladder. We removed the diverticulum
      by laparoscopic procedure and then the prostate by transurethral resection on
      September 24th, 1998. Before the diverticulectomy, we placed a ureteral stent in
      the left ureter and 8Fr Foley catheters in the diverticulum and bladder. A
      working space was made by dilation using a balloon dilator. After removing the
      diverticulum, we made 5 stitches to close the bladder wall. After the surgery, a
      22Fr Foley catheter was placed and removed on the 9th postoperative day. Patient
      had a satisfactory micturition and was discharged on the postoperative 15th day.
      Laparoscopic diverticulectomy might be a modality for symptomatic bladder
      diverticulum, because it is minimally invasive and can completely remove bladder
      diverticulum.

PMID- 11593709
TI  - [Renal transplant blood flow measurement using ultrasonic contrast agents].
AB  - We studied the renal transplant blood flow using an ultrasonic contrast agent.
      The contrast medium was injected intravenously and produced blood flow
      enhancement for at least 60 seconds. Measurements were made from the recorded
      Doppler spectra. Fourteen renal transplant recipients were investigated by color
      Doppler echography. Blood flow in the interlobular artery could be analyzed in
      all patients using a contrast, agent, as compared with 2 patients (14%) by a
      conventional method. The average maximum and minimum flow velocity of the
      interlobular arteries were 0.15 m/sec and 0.04 m/sec. In conclusion, an
      ultrasonic contrast agent is useful to accurately evaluate peripheral blood
      supply in renal transplants.

PMID- 11593710
TI  - [Continuous epidural administration of droperidol for the prevention of
      postoperative nausea].
AB  - Continuous antiemetic effect of epidural droperidol was evaluated by prospective,
      double-blinded study using 145 ASA physical status I-II patients undergoing major
      gynecological surgery. All patients received bolus epidural infusion of
      buprenorphine at the end of the operation and continuous epidural infusion of
      buprenorphine for 48 hours. Patients were divided into 3 groups, 49 patients of
      Group I received placebo, 50 patients of Group II received only bolus doses of
      droperidol 2.5 mg and the remaining 46 patients of Group III received continuous
      epidural infusion of droperidol 10 mg in 48 hours. Visual analogue scales for
      nausea, the incidence of emetic episodes and side effects were evaluated at 3 hr,
      24 hr and 48 hr postoperatively. The scores for nausea were significantly lower
      in Group III (P < 0.05) compared with Group I 24 hr after the operation. The
      incidence of emesis was significantly lower in Group III (P < 0.05) as compared
      with Group I and II 48 hr after the operation. Extrapyramidal side effects and
      sedative effects were not observed in any patients. The continuous epidural
      administration of droperidol is effective in prevention of postoperative nausea
      and vomiting and the effect lasts during its infusion with no side effects.

PMID- 11593711
TI  - [Effect of intra-operative propofol administration on post-operative serum lipid
      concentrations].
AB  - Propofol in emulsion formulation is widely used for anesthesia during operation
      and sedation in ICU. We investigated the effect of propofol used as a main
      anesthetic on post-operative serum lipid concentration. Nineteen patients with
      ASA physical status I or II scheduled for elective operations were enrolled in
      this study. We measured triglycerides and total cholesterol (pre-operatively,
      post-operatively and on post-operative day 1) along with AST, ALT and T-Bil (pre
      operatively and on post-operative day 1). Intraoperative infusion rate of
      propofol was 6.9 +/- 2.64 mg.kg-1.hr-1. Serum triglyceride concentration
      increased significantly post-operatively (P < 0.05). Serum total cholesterol
      concentration decreased significantly post-operatively and on post-operative day
      1 (P < 0.05). Serum AST concentration increased significantly on post-operative
      day 1. But there were no significant changes in ALT and T-Bil concentration.
      Additionally, no significant correlation was found between intraoperative
      infusion rate of propofol and difference in pre- and post-operative triglyceride
      concentrations (r = 0.44). The soya bean oil content of propofol solution is
      equivalent to that of 10% fat solution. With 10% fat infusion rates of below 0.1
      mg.kg-1.hr-1 (equall to propofol 10 mg.kg-1.hr-1), serum lipid concentration did
      not increase. But our results suggested that serum triglyceride concentration may
      increase significantly post-operatively after intra-operative propofol infusion
      at a rate of 4-9 mg.kg-1.hr-1.

PMID- 11593712
TI  - [Perioperative management of the patient with von Willebrand's disease].
AB  - A 67-year-old man with von Willebrand's disease, was referred to our hospital for
      operation of the lung cancer. He underwent right upper lobectomy of the lung and
      mediastinal lymph node dissection under general anesthesia. Three days before
      surgery, 1-desamino-8-D-arginine-vasopressin (DDAVP) was infused with good
      response of bleeding time shortening from 6 minutes to 3 minutes. Therefore,
      immediately before operation, DDAVP was infused. During the operation bleeding
      tendency was observed. Heat-treated factor VIII concentration and fresh frozen
      plasma were administered. Bleeding tendency was controlled. Total blood loss was
      613 ml. During intraoperative and postoperative period, factor VIII activity and
      von Willebrand factor (vWF) activity were kept at adequate levels (factor VIII:
      105-150%; vWF: 65-225%). The postoperative course was uneventful and he was
      discharged 18 days after the operation.

PMID- 11593713
TI  - [Acute myocardial infarction in the postoperative period in an elderly man with
      low coronary risk factor before the operation].
AB  - An 86-year-old man complicated by severe asthma developed myocardial infarction
      after the operation of abdominal aortic aneurysm. Emergency coronary angiography
      (CAG) revealed 99% stenosis of main trunks of left coronary artery (LMT). Because
      the patient had been without major coronary risk factors, it was difficult to
      predict coronary lesions preoperatively. Elderly patients have frequently latent
      complications not detected by usual consultation. Therefore, in elderly patients,
      we have to evaluate each individual risk factor more rigidly, and perform more
      thorough preoperative tests, including CAG.

PMID- 11593714
TI  - [A case of diaphragmatic paralysis in a patient with diabetes mellitus after
      surgery in prolonged prone position].
AB  - A 56-year-old woman with diabetes mellitus was scheduled for bilateral kidney
      lithotomy. She was in the prone position for about seven hours during operation.
      At the end of operation, arterial blood gas analysis showed PaO2 64 mmHg and
      PaCO2 44 mmHg under 100% oxygen inhalation through a face mask, and the chest x
      rays showed elevation of the right diaphragm. Her trachea was intubated again.
      The right diaphragm returned to the preoperative level by positive pressure
      ventilation on supine position. Hypoxemia disappeared when the patient was placed
      in the sitting position, and the trachea was extubated. The right diaphragm
      returned to the normal level on the 1st postoperative day, but hypoxia continued
      until the 6th postoperative day with the patient on supine position. We speculate
      that the diaphragmatic paralysis was caused by over-extension of the neck for a
      prolonged period, and that the patient might have been susceptible to nerve
      injury due to underlying diabetes mellitus.

PMID- 11593715
TI  - [Preparation of a manual for treatment of patients refusing blood transfusion].
AB  - We prepared a concise and simple manual for the treatment of a patient refusing
      blood transfusion. In this manual, we present the idea that our medical staff
      will respect the intention of adult patients but not the intention of juveniles
      below 18 years of age. If an unconscious adult patient is carrying a blood
      refusal card, we would regard the card as a document indemnifying the hospital
      from responsibility and we would treat the patient without blood transfusion.
      However, we would treat a juvenile patient below 18 years of age with blood
      transfusion if necessary, even if they and their parents refused blood
      transfusion. By following the manual, we can cope with the patient who refuses
      blood transfusion, promptly and precisely and we are rarely prosecuted by them.
      We respect the right of patients to make decisions regarding medical treatment
      and to resolve problems regarding medical expenses. We recommend that all medical
      institutions prepare a manual for the treatment of the patient refusing blood
      transfusion and officially announce the institution's policies on this matter.

PMID- 11593716
TI  - [Annual report of perioperative mortality and morbidity for the year 1999 with a
      special reference to anesthetic methods at Certificated Training Hospitals of
      Japanese Society of Anesthesiologists].
AB  - The Committee on Operating Room Safety of Japanese Society of Anesthesiologists
      (JSA) sends annually confidential questionnaires of perioperative mortality and
      morbidity to Certificated Training Hospitals of JSA. This report is on
      perioperative mortality and morbidity in 1999 with a special reference to
      anesthetic methods. Four hundred and sixty-seven hospitals reported the number of
      cases referred to anesthetic methods and total numbers of cases were 727,723. The
      incidences of cardiac arrest per 10,000 cases due to all etiology are estimated
      to be 6.77 cases in average, 5.33 cases in inhalation anesthesia, 34.26 cases in
      total intravenous anesthesia (TIVA), 5.26 cases in inhalation anesthesia plus
      epidural or spinal or conduction block, 5.29 cases in TIVA plus epidural or
      spinal or conduction block, 0.73 cases in spinal with continuous epidural block
      (CSEA), 2.85 cases in epidural anesthesia, 1.63 cases in spinal anesthesia, 2.53
      cases in conduction block and 46.51 cases in other methods. However, the
      incidences of cardiac arrest per 10,000 cases totally attributable to anesthesia
      are estimated to be 0.78 case in average, 0.51 case in inhalation anesthesia,
      1.35 cases in TIVA, 0.97 case in inhalation anesthesia plus epidural or spinal or
      conduction block, 1.51 cases in TIVA plus epidural or spinal or conduction block,
      0.73 case in CSEA, 1.71 cases in epidural anesthesia, 0.54 case in spinal
      anesthesia, 2.52 cases in conduction block and 1.08 cases in other methods. The
      incidences of severe hypotension per 10,000 cases due to all etiology are
      estimated to be 16.64 cases in average, 13.61 cases in inhalation anesthesia,
      100.36 cases in TIVA, 13.32 cases in inhalation anesthesia plus epidural or
      spinal or conduction block, 9.07 cases in TIVA plus epidural or spinal or
      conduction block, 3.65 cases in CSEA, 6.26 cases in epidural anesthesia, 7.31
      cases in spinal anesthesia, 2.52 cases in conduction block and 28.12 cases in
      other methods. On the other hand, the incidences of cardiac arrest per 10,000
      cases totally attributable to anesthesia are estimated to be 2.40 cases in
      average, 1.65 cases in inhalation anesthesia, 0.81 cases in TIVA, 3.92 cases in
      inhalation anesthesia plus epidural or spinal or conduction block, 2.77 cases in
      TIVA plus epidural or spinal or conduction block, 2.56 cases in CSEA, 3.42 cases
      in epidural anesthesia, 2.71 cases in spinal anesthesia, zero case in conduction
      block and zero case in other methods. The incidences of severe hypoxia per 10,000
      cases due to all etiology are estimated to be 5.32 cases in average, 6.7 cases in
      inhalation anesthesia, 9.17 cases in TIVA, 5.16 cases in inhalation anesthesia
      plus epidural or spinal or conduction block, 4.53 cases in TIVA plus epidural or
      spinal or conduction block, 2.56 cases in CSEA, zero case in epidural anesthesia,
      1.08 cases in spinal anesthesia, zero case in conduction block and 1.08 cases in
      other methods. On the other hand, the incidences of severe hypoxia per 10,000
      cases totally attributable to anesthesia are estimated to be 2.39 cases in
      average, 3.22 cases in inhalation anesthesia, 2.43 cases in TIVA, 2.26 cases in
      inhalation anesthesia plus epidural or spinal or conduction block, 2.77 cases in
      TIVA plus epidural or spinal or conduction block, zero case in CSEA, zero case in
      epidural anesthesia, 0.54 cases in spinal anesthesia, zero case in conduction
      block and 1.08 cases in other methods. The mortality rates of cardiac arrest per
      10,000 cases due to all etiology are estimated to be 3.56 cases in average, 2.82
      cases in inhalation anesthesia, 24.55 cases in TIVA, 1.4 cases in inhalation
      anesthesia plus epidural or spinal or conduction block, 1.51 cases in TIVA plus
      epidural or spinal or conduction block, zero cases in CSEA, 0.57 cases in
      epidural anesthesia, 0.27 cases in spinal anesthesia, zero case in conduction
      block and 42.18 cases in other methods. On the other hand, the mortality rates of
      cardiac arrest per 10,000 cases totally attributable to anesthesia are estimated
      to be 0.08 case in average, 0.09 case in inhalation anesthesia, 0.27 case in
      TIVA, 0.05 case in inhalation anesthesia plus epidural or spinal or conduction
      block, zero case in TIVA plus epidural or spinal or conduction block, zero case
      in CSEA, 0.57 case in epidural anesthesia, zero case in spinal anesthesia,
      conduction block and other methods. The outcomes of cardiac arrest totally
      attributable to anesthesia are 70.2% of full recovery without any sequelae, 10.5%
      of death within 7 days, 1.8% of vegetative state and 17.5% of unknown results
      while the outcome of critical events including severe hypotension and severe
      hypoxia totally attributable to anesthesia is 94.9% of full recovery without any
      sequelae, 0.4% of death within 7 days, 0.2% of vegetative state and 4.5% of
      unknown results. These results indicate that there are no differences in
      mortality and morbidity totally attributable to anesthesia among anesthetic
      methods in 1999 at Certificated Training Hospitals of Japan Society of
      Anesthesiologists.

PMID- 11593717
TI  - [Effects of low reactive level laser, linear polarized light and Xenon-ray
      irradiation on the stellate ganglion in dogs].
AB  - The aim of this study was to clarify the influence of low reactive level laser,
      linear polarized light and Xenon-ray irradiation on stellate ganglion activity in
      dogs. Under general anesthesia, the right stellate ganglion was exposed by
      thoracotomy. After stabilization of the hemodynamic parameters, the following
      baseline measurements were taken: mean arterial pressure (MAP), heart rate (HR),
      and right brachial artery blood flow (BABF). Experiment 1: The stellate ganglion
      was directly irradiated for 10 min with low reactive level laser, linear
      polarized light or Xenon-ray. The hemodynamic parameters were measured for 60 min
      after each irradiation. Immediately after the irradiation study, stellate
      ganglion blockade (SGB) with 0.5% mepivacaine 1.0 ml was performed. Experiment 2:
      After confirming a decrease in BABF by direct electrical stimulation on the
      stellate ganglion, the stellate ganglion was directly irradiated with low
      reactive level laser, linear polarized light or Xenon-ray. The hemodynamic
      parameters were measured for 60 min after each irradiation. Immediately after the
      irradiation study with 0.5% mepivacaine 1.0 ml was performed. The hemodynamic
      parameters were also measured for 60 min after SGB. The changes in variables were
      not statistically significant after each irradiation in the experiment 1 and 2.
      After SGB, a significant decrease in HR and a significant increase in BABF
      occurred in the experiment 1 and 2. In conclusion, this study demonstrated that
      irradiation with low reactive level laser, linear polarized light and Xenon-ray
      of the stellate ganglion did not induce sympathetic blockade in dogs.

PMID- 11593718
TI  - [Effects of enflurane on respiratory neurons of the pre-Botzinger complex in
      medullary slices of neonatal rats].
AB  - Volatile anesthetics depress respiration and neuronal activity of the central
      nervous system. Recently, a limited region of the ventral medulla (pre-Botzinger
      complex; PBC) has been assumed to be the core of respiratory rhythm generation.
      The transverse brainstem slice preparation containing PBC was used in neonatal
      rats to investigate the effects of enflurane on respiratory neurons. Enflurane
      significantly depressed the frequency and the amplitude of spontaneous
      respiratory bursts in a concentration-dependent manner. In the presence of the
      GABAA antagonist bicuculline (20 microM) and the glycine antagonist strychnine (1
      microM), the effectiveness of enflurane in reducing the activity of PBC
      diminished by 50%. These results suggest that the enflurane-induced decrement of
      spontaneous activity of respiratory neurons is partly caused by an increase in
      synaptic inhibition.

PMID- 11593719
TI  - [The effects of the fat component of propofol solution of ketogenesis during
      propofol anesthesia].
AB  - To examine the effects of the fat component in propofol solution on the fat
      metabolism during propofol anesthesia, we measured the urine ketone body (UKB)
      and blood concentrations of 3-hydroxybutyrate (3-OHBA) and glucose. The
      anesthesia was maintained with propofol, fentanyl, and vecuronium. Infusion fluid
      without glucose was used while we measured the concentration of 3-OHBA. UKB was
      detected only when the concentration of 3-OHBA was more than 400 mumol.ml-1. The
      blood concentration of 3-OHBA increased in proportion to the total amount of
      propofol solution, while UKB did not show any such relationship. Furthermore, the
      rate of increase of 3-OHBA was larger in the group whose concentration of 3-OHBA
      was higher than the normal range. The blood concentration of glucose ranged
      within the normal fasting level. There were no cases who needed special treatment
      for hyperketonemia in this study. We concluded that 3-OHBA was a more sensitive
      indicator of ketogenesis than UKB, and that ketogenesis was accelerated both by
      propofol anesthesia with the lipidemic solution of propofol and by fasting before
      surgery. The acceleration of ketogenesis was especially marked in the patients
      with hyperketonemia.

PMID- 11593720
TI  - [The influence of baricity on differential blockade with 0.5% bupivacaine spinal
      anesthesia].
AB  - We evaluated the influence of baricity on differential blockade during spinal
      anesthesia using isobaric or hyperbaric 0.5% bupivacaine. Forty ASA-PS I-II
      patients scheduled for elective surgery (orthopedic, lower abdominal and
      urologic) were divided into two groups; group H, using hyperbaric 0.5%
      bupivacaine, and group I, using isobaric 0.5% bupivacaine. Spinal anesthesia was
      performed in lateral decubitus position, using a 25-gauge Quincke needle at L2-3
      interspace, and 0.5% bupivacaine 2.0 ml was injected for 10 seconds. Patients
      were turned to supine position soon after the spinal anesthesia and the block
      levels were examined every 5 min for 30 min. Sympathetic blockade was detected by
      observer's hand, the loss of cold sensation by alcohol sponge and the loss of
      pain sensation by pinprick. Complete motor blockade was detected by modified
      Bromage scale. Significant higher sensory blockade and large number of complete
      motor block were observed in group H. Differential blockade between sympathetic
      and sensory was significant and lasted 30 min in group I, but lasted only 15 min
      in group H.

PMID- 11593721
TI  - [Analysis of difficult tracheal intubation in patients with first and second
      brachial arch syndrome].
AB  - We experienced 87 anesthetic managements of 26 patients with first and second
      brachial arch syndrome in the past 20 years. We analyzed retrospectively the
      occurrence of difficulty in tracheal intubation with these patients. The
      incidence of difficult intubation was as high as 39.5% of the cases. Furthermore
      it was quite difficult to place endotracheal tube, especially in younger children
      undergoing oral procedure. We examined the correlation among classification of
      mandibular hypoplasia (Pruzansky classification), the fusion of cervical spines
      and the degrees of difficulty in intubation for 16 patients who had had
      radiographs of skull, but we found no correlation among them. But in all the 3
      patients with the fusion of cervical spines, intubation was difficult. Therefore,
      we must perform radiographic assessment of the fusion of the cervical spine.

PMID- 11593722
TI  - [Anesthesia for electroconvulsive therapy during pregnancy--a case report].
AB  - We experienced anesthetic management for ECT in a patient with psychiatric
      disease during the third trimester of pregnancy. The 24 year-old patient had been
      on oral antipsychotics prescribed to treat schizophrenia for ten years. Her signs
      and symptoms deteiorated during pregnancy in spite of increased doses of
      antipsychotics. With tocolytic agent administered intravenously, anesthesia was
      induced by intravenous thiamylal immediately followed by intravenous
      suxamethonium for muscle relaxation. Alternative current was applied on both side
      of the head after the sufficient anesthesia had been obtained. The patient
      received intermittent mandatory ventilation by breathing mask with 100% oxygen
      during the procedure. Along with monitoring of maternal hemodynamic variables and
      arterial oxygen saturation (Spo2), fetal heart rate and uterine contraction were
      recorded by cardiotocogram throughout the procedure. At the first two treatments,
      the patient showed neither significant uterine contraction nor fetal heart rate
      changes. At the third treatment, continuous uterine contraction refractory to
      tocolysis was recorded for six minutes, resulting in fetal bradycardia. At the
      sixth treatment, general anesthesia was induced and maintained by sevoflurane in
      oxygen followed by suxamethonium for muscle relaxation. The uterine contraction
      was remarkably diminished and fetal heart rate remained unchanged during the
      procedure. In conclusion, inhalation anesthesia is beneficial for ECT in the last
      stage of pregnancy to reduce uterine contraction by potential uterine relaxation
      effect of anesthetics.

PMID- 11593723
TI  - [Sedative premedication is necessary for infants in anesthetic induction under
      the presence of mother].
AB  - We examined the necessity of sedative premedication for elective operation of
      childhood when induction was performed beside the mother. One hundred and nine
      patients (aged from 2 to 8 years) were assigned randomly to two groups; midazolam
      (0.5 mg.kg-1, orally, n = 56) was administered 45 min before induction in Group
      M, and vehicle was administered (n = 53) in Group C. The differences between the
      two groups about their calmness and behavior were investigated using double blind
      method, and analyzed according to their ages, as infants (2 to 4 years),
      kindergarteners (5 to 6 years) and school children (7 to 8 years). The
      significantly higher incidences of agitation or alertness were observed in
      infants of Group C (P < 0.05) and all other patients were calm and well sedated.
      We conclude that sedative premedication is necessary in infants even if induction
      is performed beside patient's mothers.

PMID- 11593724
TI  - [Is the bronchoscopic criteria of early lung cancer valid?].
AB  - We studied the validity of the bronchoscopic criteria of the early lung cancer
      using the surgical specimen excised between 1980 and 1999. Twenty-four cases with
      squamous cell carcinoma of the lung of clinical stage I were located subsegmental
      or more proximal bronchi and trachea, and the size less than 20 mm in greatest
      dimension. We histopathologically investigated the endoscopic features in
      relation to the width of superficial extent, the depth of cancer invasion, and
      lymph node metastasis. Tumors of the thickened type lesions less than 20 mm in
      greatest dimension showed no invasion into the cartilaginous layer and no lymph
      node metastasis. On the other hand, in the nodular and polypoid types, invasion
      beyond the cartilaginous layer was observed more or less, and lymph node
      metastasis was observed in 1 case. These cases would not be suitable for
      bronchoscopic (photodynamic) therapy. In conclusion, the bronchoscopic criteria
      of early lung cancer is valid in the thickened type, but not in the nodular type
      or polypoid type.

PMID- 11593725
TI  - [Ultrasonographical approach for the diagnosis on the depth of invasion in early
      bronchogenic squamous cell carcinoma].
AB  - It is important to evaluate the depth of invasion to determine the appropriate
      treatment for roentgenographically occult bronchogenic squamous cell carcinoma
      (ROSCC). In order to evaluate the actual significance of TUS as a diagnostic tool
      of intraluminal carcinoma invasion, we have conducted a prospective trial. TUS
      was performed on 29 lesions of ROSCCs. We ultrasonographically classified the
      degree of the depth of intraluminal invasion into 2 groups; A: "inside of
      cartilaginous layer" and B: "cartilaginous layer or over". The patients were
      treated by irradiation, photodynamic therapy (PDT) or surgical resection.
      Clinicopathological findings and response to the treatment were compared with
      this ultrasonographical classification. In the evaluation of invasion within
      cartilage, the sensitivity was 88.2%, the specificity was 77.8%, the accuracy was
      84.6%, and the positive predictive value was 88.2%. With TUS, the decision of
      treatment modality would be more appropriate.

PMID- 11593726
TI  - [Contrivance for frozen section diagnosis of early minute lung cancer during
      operation].
AB  - We reported the technique of pathological diagnosis for minute lung cancer lesion
      of early stage during operation. Target lesion for our technique may be less than
      1 cm in size and not be detected by palpation. Our technique may superior to
      usual method of frozen section of tissue specimen without fixation. At first,
      resected lung specimen was fixed by injection of 20% formalin solution subsequent
      warming by microwave oven for 40 seconds. Almost all lesions may be detected in
      proper thickness of specimen. Specimen was washed out and steeped in the 20% of
      sucrose solution for 30 to 60 seconds in order to avoid crystallization of water
      that was contained within lung specimen. Then thin sliced section of specimen was
      made by Cryostat in usual method. The minute cancer lesion was able to detect
      more easy than usual method of making frozen section of specimen. Formalin fixed
      and sucrose steeped frozen section may be able to evaluate the surgical margin
      from cancer exactly than the section made by non-fixed specimen.

PMID- 11593727
TI  - [Relationship between Noguchi's classification for small adenocarcinomas of the
      lung and tumor markers in serum].
AB  - We evaluated the relationship between Noguchi's classification for small
      adenocarcinomas of the lung and tumor markers in serum (CEA, Cyfra, SLX, CA 19-9,
      CA 125). Fifty surgically resected small peripheral adenocarcinomas measuring 2
      cm or less in greatest diameter were examined. The tumors were divided into three
      groups on the basis of Noguchi's classification: group AB of tumors belonging to
      Noguchi's classification A or B, group C of tumors belonging to Noguchi's
      classification C, and group DEF of tumors belonging to Noguchi's classification
      D, E, or F. The level of serum CEA was higher in group DEF (5.9 +/- 7.6 ng/ml)
      than in group AB (2.3 +/- 2.4 ng/ml) and group C (2.0 +/- 1.3 ng/ml). There were
      no differences in the levels of the other serum tumor markers among the three
      groups. The incidences of anormality in serum CEA and Cyfra were higher in group
      DEF (6/18 and 6/18, respectively) than in group AB (1/7 and 0/7) and group C
      (1/25 and 1/25). Although a high level of serum CEA or Cyfra is a strong
      indication that the tumor is Noguchi's classification D, E, or F of pulmonary
      adenocarcinoma, it is difficult to classify small adenocarcinomas by Noguchi's
      classification using a serum tumor marker level.

PMID- 11593728
TI  - [Fluoroscopy-assisted thoracoscopic surgery after computed tomography-guided
      bronchoscopic barium marking: a minimally invasive treatment for small peripheral
      early adenocarcinoma of the lung].
AB  - We developed a marking technique and subsequent thoracoscopic wedge resection as
      a diagnostic procedure for small peripheral lung nodule and a treatment for small
      peripheral early lung cancer. Fluoroscopy-assisted thoracoscopic surgery after
      computed tomography-guided bronchoscopic barium marking. Through CT-guided
      bronchoscopy, barium marking is done at just central to the target lesion.
      Thoracoscopic surgery is performed some days later. The barium marking was
      grasped in the forceps and resected by endostaplers under both intraoperative
      fluoroscopic and thoracoscopic guidance. All the lesions could be resected with
      enough surgical margin. This minimally invasive surgery is indicated for small
      peripheral in situ adenocarcinoma of the lung.

PMID- 11593729
TI  - [Current condition of early peripheral lung cancer and related problems].
AB  - Early peripheral lung cancer is defined as a tumor whose diameter is within 20 mm
      and that has not metastasized to lymph nodes. We developed thoracoscopic surgery
      (two windows method) in 1993. We have been conducting this thoracoscopic surgery
      in early peripheral lung cancers to identify possible indications as well as to
      clarify problems related to early peripheral lung cancer. The subjects of this
      study were 176 tumors, with diameters within 30 mm, including 97 lung cancers
      with diameters within 20 mm. Of the 97 tumors 20 mm or less in diameter, 18 were
      N 1 or more severe (N 1, 8 cases: N 2, 10 cases). One patient (N 2) died of bone
      metastasis and two patients died due to diseases other than lung cancer. Nearly
      20% of the patients with tumors 20 mm or less were in the advanced stage,
      suggesting that mediastinal lymph node resection is necessary. Based on these
      results, it is advisable to define tumors with a diameter of no more than 10 mm
      as early peripheral lung cancer.

PMID- 11593730
TI  - [Result of surgical treatment to early stage peripheral non-small cell lung
      cancer].
AB  - In the lung cancer, the announcement of the definition, the clinical behavior and
      the treatment result of the central early stage lung cancer, especially in situ
      lung cancer, have been seen. However, the definition and a clinicopathological
      concept of the peripheral lung cancer are still uncertain. The so-called small
      lung cancer of the tumor diameter 20 mm or less are peripheral lung
      adenocarcinoma. These patients' prognosis is excellent better, in contradiction
      to the prognosis of the patients with positive for pleural involvement or vessels
      invasion is worse. We studied the clinicopathological features, the Noguchi's
      classification, and prognosis of the 101 patients with small lung adenocarcinoma
      which were performed the operation, and refere about the selection of the
      operation method including the VATS and the limited operation.

PMID- 11593731
TI  - [Acceptable definition of peripheral early lung cancer].
AB  - This study was conducted to evaluate the outcome of 88 patients who underwent
      surgical resection for peripheral non-small cell lung cancers less than 20 mm in
      diameter. Twenty-one cases with lesions smaller than 10 mm had no lymph node
      metastasis, intrapulmonary metastasis, pleural dissemination, or distant
      metastasis. The 5-year survival rate of them was 100%. However, 67 patients with
      tumors larger than 10 mm showed lymph node metastasis in 14 cases, intrapulmonary
      metastasis in 3, pleural dissemination in 2 and distant metastasis in 1. And the
      5-year survival rates of patients with tumor dimensions of < or = 15 mm and < or
      = 20 mm were 77.9% and 74.4%, respectively. In addition, patients having
      adenocarcinoma categorized A and B by Noguchi's classification had no lymph node
      metastasis, intrapulmonary metastasis, pleural dissemination, or distant
      metastasis, and showed 100% of 5-year survival rate. To be defined as early
      cancers in terms of curability, it is thought that the 5-year survival rate of
      the patients with them is over 95%. Therefore, these results suggest that tumors
      smaller than 10 mm or adenocarcinoma less than 20 mm in diameter diagnosed as
      Noguchi's A and B are considered as peripheral early lung cancers.

PMID- 11593732
TI  - [Clinicopathological study of early peripheral adenocarcinoma of the lung].
AB  - Fifty surgically resected small peripheral adenocarcinomas measuring 20 mm or
      less in greatest diameter were reviewed according to Noguchi classification
      (1995). Type A (localized bronchioloalveolar carcinoma: LBAC) and type B (LBAC
      with foci of structural collapse of alveoli) showed no lymph node metastasis and
      in these two types, 5-year survival was 100%. Histologic types A and B in Noguchi
      classification are thought to be early peripheral adenocarcinoma. By further
      evaluation of preoperative imaging diagnosis, operative procedure and
      pathological study patients with early peripheral adenocarcinoma would be able to
      become candidates for limited surgery (segmentectomy or partial resection).

PMID- 11593733
TI  - [Less invasive surgery for the small size peripheral lung cancer: an indication
      and a review of VATS (video-assisted thoracic surgery) lobectomy].
AB  - According to increment of detection of the "small" size peripheral lung cancer
      measuring less than 20 mm in the greatest dimension, the "less" invasive VATS
      lobectomy has became widespread among the general thoracic surgeon. To decide on
      the indication of VATS lobectomy, the frequency of nodal metastasis and
      recurrence were examined in relation to size of the tumor. The diagnostic
      accuracy of nodal status in clinical and pathological examinations was 88% in the
      group with tumors less than 20 mm, 79% in the 21 to 30 mm group and 63% in the c
      T2 group, respectively. Also, recurrencies were experienced more frequently in c
      T2 (44%) than in c-T1 (19%). In our department, the VATS lobectomy was introduced
      under the condition as follows; the clinical stage should be limited to T1N0M0.
      Intraoperative histological examination of the locoregional lymph nodes is
      required to avoid the risk of local recurrence. In these limited conditions, the
      survival rate of VATS lobectomy is slightly superior to that of the standard
      thoracotomy in a same clinical stage. In the future, the application of this
      procedure should be investigated in older patients, and in more advanced cases.

PMID- 11593734
TI  - [Intentional limited operation for minute peripheral adenocarcinoma of the lung].
AB  - The purpose of this report is to evaluate the limited operation for peripheral
      minute adenocarcinoma of the lung. Firstly, 44 cases (47 lesions) of surgically
      resected minute peripheral lung adenocarcinoma, 10 mm or less in diameter, were
      reviewed using Noguchi's classification, and the correlation between high
      resolution CT (HRCT) images and the clinicopathological features was examined
      retrospectively. All type A and B adenocarcinomas (n = 14) had no recurrence and
      all cases were the air containing type by HRCT. Lymph node metastasis and
      lymphatic/vascular involvement were detected with type C, D, E, F and 3 cases
      among them were died for recurrence. Based on those results, from April 2000,
      intentional limited operation was prospectively performed for 14 patients (16
      lesions) with peripheral nodule showing ground-glass opacity on HRCT. The
      pathological findings were type A (n = 9), type B (n = 5), and atypical
      adenomatous hyperplasia was one case (If the findings were confirmed type C, D,
      E, F by permanent section diagnosis, VATS lobectomy will be performed). We
      recommend limited operation should be performed in only type A or B
      adenocarcinoma and permanent section diagnosis is necessary to determine whether
      or not.

PMID- 11593735
TI  - [Preoperative PDT for early stage lung cancer accompanied with infiltration to
      the central airway].
AB  - For the treatment of central type lung cancers, it is often necessary to perform
      bronchoplasty or bi-lobectomy even in early stage cases in which tumor invasion
      is found at the bronchial bifurcation. To solve this contradictory situation, we
      applied PDT for central type early stage lung cancer to reduce the extent of
      superficial infiltration, enabling a simple surgical technique or decreasing the
      amount of resected lung parenchyma. Among 7 patients, the simplification of
      surgical technique and reduction of the range of resection were possible in 2
      cases each respectively. However, these objectives were not satisfied in the
      remaining 3 cases and the operations performed were those that had been
      originally scheduled before PDT. The current problems are the establishment of
      appropriate laser irradiation technique and accurate assessment for extension of
      invasion.

PMID- 11593736
TI  - [Order-made therapy for early lung cancer patients].
AB  - To give optimal treatment to the patients with early lung cancer, we are trying
      to establish two new techniques to select the patients of poor prognosis and
      sensitive to the chemotherapy. To pick up the patients of poor prognosis
      nevertheless the early stage of their lung cancer, we are developing a new method
      to detect cancer cells floating in the peripheral blood flow with RT-PCR using
      cancer specific mRNA. To choose optimal chemotherapy regimens, we have
      established a new chemosensitivity testing (collagen gel droplet embedded culture
      drug sensitivity test: CDDST) for non-small cell lung cancer (NSCLC). Median
      survival time (MST) of the patients (n = 11) with unresectable NSCLC, who were
      given optimal chemotherapy according to CDDST, was 15.8 months and MST of those
      (n = 16) who did not have any sensitive agents according to CDDST was 5.6 months.
      There was significant difference between these two groups (p = 0.0048; logrank).

PMID- 11593737
TI  - [Thoracoscopic lung resection for a peripheral lung cancer by a single surgeon
      with a voice-controlled robot].
AB  - Thirty patients with a peripheral lung cancer underwent consecutive thoracoscopic
      lung resections with a voice-controlled robot between October 1998 and February
      2001. The patients with a high risk such as cardio-pulmonary dysfunction or the
      patients aged 80 years or older were included. Patients with stage I cancer of
      the right lung in which lobectomy with lymph node dissection was anticipated were
      also included. Thirty thoracoscopic procedures were performed by a single surgeon
      using a voice-controlled robot. Thoracoscopic lung resection by a single surgeon
      with a voice-controlled robot was achieved in 27 patients. The postoperative
      follow-up period ranged from 3 months to 42 months. In all patients,
      thoracoscopic procedures without no need for a human assistant were achieved.
      There were no survival differences between the wedge resection group and
      lobectomy group, in the patients having adenocarcinoma and patients having
      squamous cell carcinoma, and elderly patients and young group patients.
      Complications related or unrelated to the maneuvers of a voice-controlled robot
      were not noted. Postoperative complications occurred in 4 patients (atelectasis
      2, postoperative dementia 2). All of the events resolved within one week.
      Thoracoscopic lung resection such as wedge resection or lobectomy by a single
      surgeon with a voice-controlled robot may be feasible in selected patients with
      lung cancers. Its application must be confirmed by further studies.

PMID- 11593738
TI  - [Surgical treatment of chronic pulmonary thromboembolism caused by a cavernous
      hemangioma at the lower limb].
AB  - A 48-years old man complained of dyspnea and was admitted to the hospital. Chest
      enhanced CT confirmed the presence of the thrombus in the pulmonary artery.
      Cardiac catheterization showed severe pulmonary hypertension (mean PAP 75 mmHg).
      ATIII level, protein C and S antigen were within normal range. Anticardiolipin
      antibody and lupus anti-coagulant determination were negative. He was diagnosed
      as chronic pulmonary thromboembolism, and underwent pulmonary
      thromboendarterectomy via median sternotomy under deep hypothermic intermittent
      circulatory arrest. At the same time IVC filter was inserted. The origin of the
      thrombus was not detected before operation, but after surgery, MR angiography of
      total body showed a cavernous hemangioma at left lower limb. We speculated this
      lesion was the origin of pulmonary embolism.

PMID- 11593739
TI  - [A case report of the dissecting aneurysm of ascending aorta, which was surmised
      to be developed after aortic valve replacement].
AB  - Bentall operation was performed for the ascending aortic dissection in the
      patient of a 70-year old man, who had undergone aortic valve replacement (AVR)
      for aortic valve regurgitation 7 years ago. At the AVR, the diameter of the
      ascending aorta was 50 mm on CT. During the follow up period after AVR, the
      ascending aorta was gradually developed to 95 mm in diameter without any
      symptoms. During the reoperation, entry was recognized on the prior aortotomy
      reinforced with felt-strips and the intimal flap was thickened. These situations
      suggested that the aortic dissection might be occurred just or early after AVR,
      and the reinforcement of aortotomy using felt-strips and AVR could not prevent
      progression of aortic root enlargement and dissection. From some previous reports
      about ascending aortic dissection after AVR, an adequate surgical treatment for a
      dilated ascending aorta (40-50 min) should be required at the same time of AVR.

PMID- 11593740
TI  - [An unconscious patients with ascending aortic aneurysm accompanied by aortic
      regurgitation successfully treated by emergency operation after cardiopulmonary
      resuscitation].
AB  - A-37-year-old woman in shock condition was transferred to our hospital after
      cardiopulmonary resuscitation for ventricular fibrillation. She was unconscious
      and suspected of suffering ischemic brain damage, with pathologic reflexes and
      weak brain stem reflexes. Brain CT scan showed cerebral edema without hemorrhage
      or infarction and an electroencephalograph revealed slow alpha-theta waves. Chest
      CT scan and echocardiogram showed ascending aortic aneurysm with sever aortic
      regurgitation. An emergent operation was performed for progression of heart
      failure. There were no distortion or dilatation of the sinus of Valsalva and
      annuloaortic ectasia and aortic valve leaflets were almost normal. We considered
      that the aortic valve dysfunction was cause by dilatation of the sinotubular
      junction. Ascending aortic and aortic valve replacement were carried out to
      shorten cardiopulmonary bypass time and to prevent the progression of brain
      damage. Mild hypothermia was employed as a neuroprotective procedure for three
      days after surgery. The patient's neurological symptoms, which were right
      hemiparesis, facial apraxia and motor aphasia, improved and she was discharged
      from the hospital on foot without any neurological complications on the 47th
      postoperative day and returned to work after two months.

PMID- 11593741
TI  - [A structural view of signal transduction: extracellular matrix-receptor/adhesion
      molecule-cytoskeleton].

PMID- 11593742
TI  - [Signal transduction of growth factor mediated by heparin/heparan sulfate].

PMID- 11593743
TI  - [Structural studies of the proteins targeting to adhesion molecules and
      receptors].

PMID- 11593744
TI  - [Membrane associating protein domains: a new paradigm of phosphoinositide binding
      domains].

PMID- 11593745
TI  - [Cofilin family and gelsolin family: the protein fold which severs actin
      filaments].

PMID- 11593746
TI  - [Auto-inhibition mechanism of proteins in signal transduction].

PMID- 11593747
TI  - [Structure and function of membrane, rafts, and their associated proteins].

PMID- 11593748
TI  - [Recent advance on the study of memory and gene expression: roles of protein
      synthesis on the early phase of cerebellar LTD].

PMID- 11593749
TI  - [The mechanism for dendritic localization of alpha CaMKII mRNA].

PMID- 11593751
TI  - [Acquisition of structural data of biological macromolecules: how to utilize
      PDB].

PMID- 11593750
TI  - [Post sequence genome analysis of Escherichia coli].

PMID- 11593752
TI  - [The mechanism of enhanced platelet intracellular calcium mobilization stimulated
      by serotonin--in the pathophysiology of mood disorders].
AB  - It has been reported that platelet intracellular calcium (Ca) response stimulated
      by serotonin (5-HT) is enhanced in unmedicated patients with some types of mood
      disorders compared to normal subjects. However, the mechanism of this enhancement
      has not been elucidated. In this study, at first, I examined whether the enhanced
      5-HT-induced Ca response was specific to some types of mental disorder. Then, the
      relationship between the 5-HT-induced platelet intracellular Ca rise and the
      density of 5-HT2A receptors on the platelets of normal subjects was investigated.
      Furthermore, effects of modulators of two main signal transduction systems,
      protein kinase C (PKC) and calmodulin (CaM), on 5-HT-induced platelet
      intracellular Ca response in the platelets of normal subjects were examined. As a
      result, the specificity to bipolar disorder among several psychiatric disorders
      was observed in enhanced 5-HT-induced Ca mobilization. There was no correlation
      between Ca response to 5-HT and the Bmax of 5-HT2A receptors. Pretreatment with
      PKC activator (PMA) dose-dependently reduced the Ca response induced by 5-HT,
      while pretreatment with CaM antagonist (10-30 microM W-7), myosin light chain
      kinase inhibitor (30 microM ML-9) or Ca/CaM-dependent protein kinase II inhibitor
      (10 microM KN-93) increased the Ca response with no remarkable changes in basal
      Ca level. But PKC inhibitors (bisindolylmaleimide II and staurosporine) failed to
      increase the Ca response at every dose. Pre-incubation with 10 mM lithium reduced
      the enhanced Ca response to 5-HT induced by 30 microM W-7. These findings suggest
      the possibility that calmodulin dysfunction might be involved in the mechanism of
      enhanced intracellular Ca response to 5-HT in bipolar disorder.

PMID- 11593753
TI  - [Expression of beta 2 glycoprotein I, the major target antigen for anti
      cardiolipin antibodies, in human endothelium].

PMID- 11593754
TI  - [Effect of hypothermia on apoptosis in neuronal cells].

PMID- 11593755
TI  - [Myocyte apoptosis in catecholamine-induced cardiomyopathy].

PMID- 11593756
TI  - [Analysis of the pathogenesis of organ specific autoimmune diseases in transgenic
      rats carrying the env-pX gene of HTLV-I].

PMID- 11593757
TI  - [GRK mRNA expression of peripheral lymphocytes reflects the severity of
      congestive heart failure].

PMID- 11593758
TI  - [Mechanism of expression of matrix metalloproteinase-23 (MMP-23) in rat ovary].

PMID- 11593760
TI  - [The 26th meeting of the Hokkaido Society for Rheumatology].

PMID- 11593759
TI  - [Talks on evaluation of students' writing (discussion)].
AB  - We talked about the evaluation of students' writing; this is thought to be
      difficult for teachers. We have a class "history of medicine" for freshmen in the
      second semester of the medical course. Students give lecture by themselves on
      famous historical persons in medicine such as Hippocrates, Vesalius, Pasteur and
      Sackett, referring to their historical significance in present medicine. As the
      final work of the subject they write report on "clinical medicine or medical
      researches 20 years in future and myself". We talked generally about educational
      evaluation in various aspects, concerning the methods for writing. We discussed
      mainly on two themes--ability to write and originality in thinking. We give a
      larger point to the originality, which correlates to ability to write, though we
      feel difficult in evaluating students' originality only by reading their reports.
      We also emphasize the importance of active interaction between students and
      teachers, and to evaluate educational activities of teachers in Japanese
      universities.

PMID- 11593761
TI  - Perspectives on the integrative functions of the 'sympatho-adrenomedullary
      system'.
AB  - An historic survey is given of the gradual change of views and concepts
      concerning how the sympatho-adrenomedullary system is organized and operates:
      While it for nearly a century was considered to merely exhibit more or less
      generalized activation-inhibition responses, experimental studies during the last
      50 years have revealed how it instead constitutes a highly sophisticated
      instrument for control, engaged in a variety of differentiated response patterns
      by which the brain controls events in major organ systems, down to include their
      cellular-molecular levels of organisation.

PMID- 11593762
TI  - The three-dimensional structure of neurons in the guinea pig inferior mesenteric
      and pelvic hypogastric ganglia.
AB  - The three-dimensional (3-D) morphology of sympathetic inferior mesenteric
      ganglion (IMG) neurons and sympathetic-parasympathetic pelvic hypogastric
      ganglion (PHG) neurons was studied using confocal laser scanning microscopy. Cell
      bodies of IMG neurons were disc-shaped and were arranged orderly in layers. The
      dendritic arbor of individual neurons was confined to a plane with a thickness
      that did not exceed the thickness of the parent cell body. The actual dendritic
      surface area (71,400 micron 2) and volume (81,500 micron 3) of the IMG neurons
      were up to 100-fold larger than previously reported for similar sympathetic
      neurons using data of 2-D measurements and estimations of the third dimension.
      PHG neurons had a much smaller dendritic surface area (4100 micron 2) and volume
      (2400 micron 3) compared to IMG neurons. The ratio dendritic/somal surface area
      for individual IMG and PHG neurons ranged from 5:1 to 14:1 and from 0.1:1 to 6:1,
      respectively. The total dendritic path-length was 8-42 times greater for IMG than
      for PHG neurons. Neurons in the IMG were either stellate with radiating dendrites
      or bipolar-shaped with dendrites emerging from the two poles of the cell body.
      Neurons in the PHG were of two morphological types. One type (nearly 2/3 of all
      the imaged PHG neurons) had two to seven relatively long dendrites and an axon;
      the other type had only one to three short unbranched dendrites and an axon. The
      spatial organization of neurons within the ganglia and the structural features of
      individual neurons are likely to have important implications regarding
      connectivity patterns between neurons within the ganglion as well as on how
      information is processed by the ganglion.

PMID- 11593764
TI  - Transneuronal retrograde dual viral labelling of central autonomic circuitry:
      possibilities and pitfalls.
AB  - Viral retrograde transneuronal labelling has become an important neuroanatomical
      tract-tracing tool for characterization of limbic neuronal networks. Recently,
      dual viral retrograde transneuronal labelling has been introduced; a method
      employing differential transgene expression of two genetically engineered virus
      strains to identify double infected cells with selective antibodies. In this way,
      interactions of parallel networks can be revealed. The use of this method will
      increase the understanding of the function of the limbic system, for example in
      the maintenance of metabolic homeostasis, but is associated with limitations
      related to the use of genetically engineered virus strains. Virulence, speed of
      replication and retrograde transport may be affected by the insertion or deletion
      of genes in the viral genome. Moreover, the rate of replication and transport can
      be affected by the immune system of the host and competition between the two
      viruses. There may be selective affinity of the virus strain for the sympathetic
      or parasympathetic systems. False negative results are the most important risk in
      dual viral labelling addressed in this review. Several control experiments are
      presented that can help to reduce the risk of obtaining false negative results.

PMID- 11593763
TI  - Activation of adenosine A1 receptors by drugs to lower plasma glucose in
      streptozotocin-induced diabetic rats.
AB  - To examine the role of the adenosine A1 receptor in glucose regulation in the
      absence of insulin, the present study investigated the changes of plasma glucose
      in male streptozotocin-induced diabetic rats (STZ-diabetic rats) using
      dipyridamole to increase endogenous adenosine and N6-cyclopentyladenosine (CPA)
      to activate the adenosine A1 receptor. Intravenous injections of dipyridamole or
      CPA induced a dose-dependent decrease of plasma glucose in fasting STZ-diabetic
      rats. Plasma glucose lowering action of dipyridamole, like that of CPA, was
      inhibited in a dose-dependent manner by pre-treatment with 8-cyclopentyl-1,3
      dipropylxanthine (DPCPX) or 8-(p-sulfophenyl)theophylline (8-SPT) at which block
      the adenosine A1 receptors. Action of the adenosine A1 receptors can thus be
      considered. In isolated skeletal muscle, CPA enhanced the glucose uptake in a
      concentration-dependent manner. Blockade of this action by DPCPX and 8-SPT again
      supported the mediation of the adenosine A1 receptor. Also, CPA produced an
      increase of glycogen synthesis in isolated soleus muscle. Moreover, CPA decreased
      plasma triglyceride and cholesterol levels significantly in STZ-diabetic rats.
      These results suggest that activation of adenosine A1 receptors can increase
      glucose utilization in peripheral tissues by increasing tissue uptake and
      glycogen synthesis to lower plasma glucose in rats lacking insulin.

PMID- 11593765
TI  - The sympathetic adrenomedullary system, but not the hypothalamic-pituitary
      adrenal axis, participates in aorta adaptive response to stress: nitric oxide
      involvement.
AB  - Stress induced a decrease in the reactivity of the aorta to noradrenaline (NA),
      as a consequence of an endothelial nitric oxide (NO) system hyperactivity. The
      main characteristic of the stress response is activation of the hypothalamic
      pituitary-adrenal (HPA) axis and sympathetic adrenomedullary (SA) system. The
      participation of the HPA axis and SA system in the decreased reactivity to NA in
      the aorta of rats exposed to 4-h immobilization was investigated. Concentration
      response relationships for NA were obtained in the aorta, with and without
      endothelium, isolated from normal and stressed rats, following these procedures:
      (1) in the absence and presence of L-NAME; (2) after adrenalectomy (ADX) or not,
      in the absence or presence of L-NAME; (3) ADX rats treated or not with
      corticosterone; (4) ADX associated with stress; and (5) treated or not with
      reserpine. The reactivity of aorta without endothelium was unaffected by the
      procedures. The reactivity of aorta with endothelium was decreased by either
      stress or ADX. This effect was reversed by both L-NAME and corticosterone. ADX
      did not potentiate the decrease in the aorta reactivity induced by stress.
      Reserpine did not change the reactivity of aorta with endothelium from normal
      rats, but prevented the decrease in reactivity induced by stress. It is concluded
      that the HPA axis participates in endothelium-dependent modulation of aorta
      reactivity in normal conditions and that the SA system participates in
      hyperactivity of the endothelial NO-system induced by stress, which is
      responsible for the decreased aorta reactivity to NA.

PMID- 11593766
TI  - Nonlinear measures of heart rate time series: influence of posture and controlled
      breathing.
AB  - In this study, we investigated measures of nonlinear dynamics and chaos theory in
      regards to heart rate variability in 27 normal control subjects in supine and
      standing postures, and 14 subjects in spontaneous and controlled breathing
      conditions. We examined minimum embedding dimension (MED), largest Lyapunov
      exponent (LLE) and measures of nonlinearity (NL) of heart rate time series. MED
      quantifies the system's complexity, LLE predictability and NL, a measure of
      deviation from linear processes. There was a significant decrease in complexity
      (P < 0.00001), a decrease in predictability (P < 0.00001) and an increase in
      nonlinearity (P = 0.00001) during the change from supine to standing posture.
      Decrease in MED, and increases in NL score and LLE in standing posture appear to
      be partly due to an increase in sympathetic activity of the autonomous nervous
      system in standing posture. An improvement in predictability during controlled
      breathing appears to be due to the introduction of a periodic component.

PMID- 11593767
TI  - Heterogeneity in mechanisms underlying vasodilatory responses in small arteries
      of the rat hepatic mesentery.
AB  - We have characterised nerve-mediated vasodilations in small arteries of the rat
      hepatic mesentery. Stimulation of sympathetic nerves (10 Hz, 10 s) produced a
      vasodilation which was abolished by the beta-adrenoceptor antagonist, propranolol
      (2 x 10(-6) M), but was unaffected by NG-nitro-L-arginine methyl ester (L-NAME,
      10(-5) M). Stimulation of sensory nerves produced a large vasodilation that was
      abolished by capsaicin (10(-6) M). This vasodilation was unaffected by L-NAME
      (10(-5) M), but significantly reduced by the calcitonin gene related peptide
      (CGRP) antagonist, CGRP8-37 (10(-6) M), or inhibition of adenylate cyclase
      (SQ22356, 2 x 10(-5) M; 2',5'-dideoxyadenosine, 2 x 10(-4) M). Stimulation of
      cholinergic nerves produced a small vasodilation which was significantly reduced
      by scopolamine (10(-6) M). Expression of mRNA for CGRP1 receptors, muscarinic m2,
      m3 and m5 receptors and neurokinin1 (NK1) and NK3, receptors was detected.
      Perivascular nerves were immunoreactive for CGRP and substance P. No role was
      found for substance P, neuronal NO, ATP or adenosine in nerve-mediated responses.
      L-NAME (10(-5) M) potentiated vasoconstrictions following sympathetic nerve
      stimulation. This effect was reversed by L-arginine (10(-3) M) and cromakalim
      (10(-6) M) and mimicked by glybenclamide (10(-5) M), thus implicating KATP
      channels. Vasodilation in response to sensory nerve stimulation was directly
      proportional to the level of preconstriction, while vasodilation in response to
      neurogenic or applied acetylcholine was inhibited at high levels of
      preconstriction. We hypothesize that, under conditions of intensive
      vasoconstriction, some endothelial-dependent vasodilations may be less important
      than vasodilations activated directly through the smooth muscle.

PMID- 11593768
TI  - [Thoughts on hospital length of stay after tonsillectomy].

PMID- 11593769
TI  - [Allergies: deficits in diagnosis and therapy].

PMID- 11593770
TI  - [Hemorrhage after tonsillectomy. Analysis of 229 cases].
AB  - BACKGROUND: In Germany a hospital stay of 6 days following tonsillectomy is
      recommended. Our retrospective study aimed to evaluate the incidence of
      hemorrhage following tonsillectomy with regard to the safety of a shorter
      hospital stay. PATIENTS AND METHODS: 5474 patients of our clinic who underwent
      tonsillectomy between 1988 and 1998 were enrolled in our study. Additionally, 65
      patients with hemorrhage following tonsillectomy elsewhere were included.
      RESULTS: Postoperative hemorrhage occurred in 145 (2.65%) of our patients, 7
      patients underwent recurrent treatment, in 97% suture ligation was sufficient.
      Primary bleeding (< 24 h) occurred in 79.7% of our patients. A 42-month old boy
      died at home due to massive bleeding 6 days following surgery. In this particular
      case, we strictly recommended postpone dismission because the boy had recurrent
      episodes of bleeding the days before. Postoperative hemorrhage after
      tonsillectomy performed elsewhere had to be treated in most cases 7-8 days
      postoperatively. Suture ligation of bleeding vessels was not sufficient in 21%
      and ligature of the external carotid artery mandatory. In these cases were
      usually found signs of deep necrosis. CONCLUSION: Due to the risk of life
      threatening bleeding tonsillectomy should be performed as an inpatient procedure.
      The time of hospital stay should be related to the results obtained by self
      evaluation and definition of risk factors. Readmission of patients with
      hemorrhage after dismission should be recommended. The follow-up has to be
      extended as long as the healing process continues.

PMID- 11593771
TI  - [Otalgia and tinnitus in patients with craniomandibular dysfunctions].
AB  - AIMS OF THE STUDY: The high prevalence of ear, nose, and throat symptoms in
      patients with craniomandibular disorders seems to depend on the connection
      between both phenomena. The present study evaluates the connection between
      craniomandibular disorders (CMD) and otalgia or tinnitus, investigates the
      correlation between specific diagnoses of CMD with otalgia or tinnitus, and
      estimates the effects of treatment of CMD on these ear symptoms. PATIENTS AND
      METHODS: The information from case histories, clinical examinations, and
      treatment results of 221 patients with CMD were coded and evaluated by computer.
      All patients received conservative treatment with occlusal splints, training in
      self-observation of parafunction, massage of the masticatory muscles, and heat
      therapy. At least 1 year after the first examination, all patients were
      reevaluated. According to their complaints, the patients could be divided into
      three groups: (1) CMD patients without ear symptoms (n = 134 = 61%), (2) CMD
      patients with otalgia (n = 80 = 37%), and (3) CMD patients with tinnitus (n = 8 =
      3.8%) (one patient with tinnitus and otalgia). RESULTS: Otalgia correlated
      significantly with CMD and the specific CMD diagnoses of anterior disk
      displacement (ADD) without reduction and osteoarthrosis. Of the reevaluated
      patients with otalgia, 90% had no ear pain and 10% reported reduced or less
      frequent ear pain. Only one of the eight cases with tinnitus noted reduced
      noises; the remaining seven perceived no influence on their ear noises from
      therapy. CONCLUSIONS: Due to the treatment results, otalgia has to be interpreted
      as a possible symptom of CMD and not as a separate diagnosis.

PMID- 11593772
TI  - [Hyperbaric oxygenation in early treatment of sudden deafness].
AB  - BACKGROUND: The treatment of sudden deafness with hyperbaric oxygenation (HBO) is
      a new method, which is a routine application in some German centers and subject
      to contraindications can be assessed as relatively reliable. PATIENTS AND
      METHODS: In a retrospective study, data were analyzed from 49 patients who had
      received primary HBO therapy because of sudden deafness (up to 3 weeks old). In
      comparison to the standard infusion therapy according to Michel, the primary HBO
      therapy led to inferior results (no change in hearing: right ear 63.88%, left ear
      60.98%; improvement in hearing: right ear 22.49%, left ear 21.71%; decrease in
      hearing: right ear 13.64%, left ear 17.32%). RESULTS: Considering the spontaneous
      remission of sudden deafness, neither the results of the infusion therapy nor
      those of the hyperbaric oxygenation surpass the rate of complete spontaneous
      remission. On the basis of our research, primary treatment of "fresh" sudden
      deafness with hyperbaric oxygenation cannot be recommended. CONCLUSIONS: The
      question remains open whether HBO as a secondary treatment for sudden deafness
      leads to improvements for the patient after unsuccessful standard therapy.

PMID- 11593774
TI  - [Possible treatments of glottic spasm].

PMID- 11593773
TI  - [Transplants from the shoulder-back region].
AB  - BACKGROUND: In spacious or multilayered tissue losses and cases of multiple
      locations of defects, a large amount of tissue with different components such as
      skin, fatty tissue, and muscle is required for proper reconstruction. A donor
      area which can meet these demands is the shoulder-back region with the
      subscapular vessel, which arises from the axillary artery. PATIENTS AND METHODS:
      We report our clinical experience with 12 patients in whom we reconstructed
      defects with transplants from this region. RESULTS: Our anatomic investigation
      and measurements provided proof of a constant anatomy of the vessels with a
      length of the vascular pedicle and a vascular diameter suitable for microvascular
      anastomosis. Based on our clinical experience, the scapular, parascapular, and
      latissmus dorsi muscle transplants are very suitable for the reconstruction of
      very large superficial defects or for the augmentation of multilayered defects of
      the upper aerodigestive tract. CONCLUSIONS: A main advantage of the transplants
      from the shoulder and back region is the possibility of combining several
      transplants with a wide variety of tissue combinations with one vascular pedicle
      for a single-step reconstruction of multiple defects of the oral cavity and the
      pharynx.

PMID- 11593775
TI  - [Combined radiochemotherapy in locally advanced nasopharyngeal carcinoma].
AB  - BACKGROUND: Nasopharyngeal cancer (NPC) is a tumor of epidermoid origin with an
      entirely different biological behavior than other carcinoma of the head and neck
      region. PATIENTS/METHODS: A retrospective analysis was performed in 93 cases with
      locally advanced NPC treated with induction chemotherapy followed by radiation
      therapy (RT; 79 patients) or concomitant RT and chemotherapy. RESULTS: Totally 66
      patients (71%) achieved a complete response (CR), 68% of the patients treated
      with induction chemotherapy followed by RT, 86% with concomitant
      chemoradiotherapy. After a median follow-up of 5.5 years 28 out of these 66
      relapsed, 25 of them locoregionally. Median time to progression was 22.5 months,
      median overall survival (OS) 45 months, 5-year actuarial survival was 41.5%. Age,
      T and N classification, histological type and type of chemotherapy were
      independent significant factors for OS. CONCLUSIONS: Combined chemotherapy and RT
      in patients with locally advanced NPC result in a high CR rate. The main problem
      remains the locoregional control. Randomized studies are needed in order to
      define the optimal use of chemotherapy in combination with RT.

PMID- 11593776
TI  - [Rare audiometry findings in progressive, monosymptomatic low frequency
      deafness].
AB  - BACKGROUND: Objective audiometric methods such as the measurement of otoacoustic
      emissions and auditory evoked potentials (click evoked and notched-noise auditory
      evoked brainstem potentials, auditory evoked cortical potentials) can provide
      helpful information. However, information derived from the individual test is
      limited and each method contains specific restrictions. To illustrate the
      possible audiometric pitfalls this work presents a case history. CASE REPORT: The
      puretone audiometry showed a severe hearing loss at low frequencies up to 2 kHz,
      a slight hearing loss for higher frequencies up to 6 kHz and almost normal
      hearing thresholds above 6 kHz. Transitory evoked otoacoustic emissions could not
      be detected. While the auditory evoked brainstem responses (ABR) using click
      stimuli showed a normal pattern no reproducible responses could be derived using
      the notched-noise technique. Auditory evoked cortical potentials exhibited a
      normal N1/P2-complex and were detectable down to stimulus levels 0-20 dB above
      the individual hearing threshold. DISCUSSION: Click-evoked auditory evoked
      brainstem potentials are widely regarded as the "gold-standard" of objective
      audiometry. The example presented in this work shows that in special cases it may
      provide false negative results. In these special cases auditory tone-evoked
      cortical potentials may provide better objective information. When objectively
      assessing the determination of the hearing threshold it may be necessary not only
      to use all electrophysiological measurements but also to know their methodical
      restrictions and pitfalls.

PMID- 11593777
TI  - [Mesenchymal chondrosarcomas of the facial skull].
AB  - A 13-year-old girl suffered from a mesenchymal chondrosarcoma of the left
      maxilla. The therapeutic options and the prognosis for this disease are described
      with respect to the currently known 72 cases in the literature. Mesenchymal
      chondrosarcomas are rare tumors of the bone and soft tissue. The first clinical
      symptom is a painless swelling of the facial skull. They occur largely in the 2nd
      and 3rd decades of life, preferentially in males. Radiological criteria for the
      identification of this type of tumor include focal ossification areas which are
      accompanied by non-calcified regions. Complete surgical removal of the tumor is
      the therapy of choice. Pre- and postoperative chemotherapy can have a beneficial
      effect. The final outcome of the disease is difficult to evaluate since late
      complications (e.g., reoccurrence and/or metastases) appear even after 20 years
      and only a small number of cases have been reported. At present, the 5-year
      survival rate is reported to be 54-82% and the 10-year rate 28-56%.

PMID- 11593778
TI  - [Differential perilymph fistula diagnosis].
AB  - If sudden unilateral deafness accompanied by vertigo and spontaneous nystagmus on
      the afflicted side occurs during birth, a perilymph fistula with rupture of the
      round window membrane caused by pressure has to be considered. A 35-year-old
      pregnant patient was presented with the aforementioned symptoms on the day she
      gave birth to triplets. During examination, surditas and a paranasal
      hyposensitivity were found on the right side. Furthermore, a spontaneous
      nystagmus on the affected side occurred which was not suppressed by fixation. The
      nystagmus was apparent as a direction-fixed gaze nystagmus. Saccades during
      smooth pursuit testing as well as a lack of the auriculofacial reflex during
      contralateral stimulation of the deaf ear could be observed. Magnetic resonance
      imaging (MRI) of the skull revealed a fresh hemorrhagic cavernoma of the
      cerebellar pedunculi. This rare lesion caused a nerve compression of the fifth
      and eighth cranial nerve due to perifocal edema. Neurosurgical intervention was
      not necessary because of subsequent spontaneous resorption of the lesions and
      abatement of the deafness within a few days.

PMID- 11593779
TI  - [Unilateral exophthalmos and pulse synchronous mechanical noise via the orbits.
      Post-traumatic cavernous sinus fistula].

PMID- 11593780
TI  - [Noninvasive evaluation of laryngeal function].

PMID- 11593781
TI  - [Therapeutic freedom versus scientific mandatory cost saving].

PMID- 11593782
TI  - [Tinnitus retraining therapy. Indications and treatment goals].

PMID- 11593783
TI  - [Three infants with epidural hematoma].
AB  - Three infants, two boys aged 10 months and one girl aged 5 months, developed
      drowsiness and emesis within a few hours of a fall (after which they had not lost
      consciousness). Radiological examination revealed an epidural haematoma which was
      treated with emergency decompression. The children subsequently made a good
      recovery. An epidural haematoma is a potentially life-threatening event. More
      than 20% of all cases of epidural haematoma occur in childhood. In contrast with
      distinct symptoms in most adults and older children, an epidural haematoma in
      infancy can have a minimum of symptoms. The open fontanelle means compression
      occurs less rapidly, but consequently blood loss can be greater, leading to acute
      anaemia, hypovolaemic shock and consumptive coagulopathy.

PMID- 11593784
TI  - [Erythromycin for premature rupture of membranes is beneficial for infant].
AB  - In the 'Overview of the role of antibiotics in curtailing labour and early
      delivery' (ORACLE I)-trial in women with premature rupture of membranes, the use
      of erythromycin was found to be associated with a decrease in the primary
      composite outcome (neonatal death, chronic lung disease or major cerebral
      abnormality on ultrasound; p = 0.08) and in single adverse neonatal outcomes (p =
      0.02) when compared to placebo. The positive results were more significant in the
      singleton group (p = 0.02 for the composite outcome), while no effects were found
      in twin pregnancies. The combination of amoxycillin and clavulanic acid, with or
      without erythromycin, was associated with some improvements in outcome, but was
      also accompanied by a higher rate of neonatal necrotising enterocolitis. Another
      trial (ORACLE II) found no effects of antibiotic use in women with premature
      labour with intact membranes. Although both trials were of good quality, the
      stratification into singleton and twin pregnancies should have been done more
      consistently. Because premature rupture of membranes in singleton pregnancies is
      more likely to be associated with a pre-existing infection than in multiple
      pregnancies, the potential benefit of treatment with antibiotics is larger in
      singleton pregnancies.

PMID- 11593785
TI  - [Urinary tract infections in women with diabetes mellitus].
AB  - Women with diabetes mellitus (DM) have asymptomatic bacteriuria (ASB) and urinary
      tract infections (UTIs) more frequently than women without DM. For type 1
      diabetes mellitus, risk factors for asymptomatic bacteriuria include a longer
      duration of diabetes, peripheral neuropathy and macroalbuminuria. For type 2
      diabetes, the risk factors are higher age, macroalbuminuria and a recent
      symptomatic UTI. Poorly-controlled diabetes and residual urine after urination
      are no risk factors. The most important risk factor for a UTI in type 1 diabetes
      patients is sexual intercourse. In type 2 diabetes patients the major risk factor
      is the presence of asymptomatic bacteriuria. This higher prevalence does not
      appear to be based on a difference in virulence of the causative microorganism.
      Differences in host response may explain this higher prevalence: E. coli with
      type 1 fimbriae adhere better to uroepithelial cells in women with DM than to
      those in women without DM; women with DM and ASB have lower urinary cytokine
      concentrations and leukocyte counts compared to women without DM and ASB; in
      vitro studies show that E. coli grow better when glucose is present in urine.
      There is no consensus on whether ASB should be treated in these patients. There
      are indications that UTIs in diabetes patients should be treated as complicated
      UTIs.

PMID- 11593786
TI  - [Primary pulmonary hypertension: new treatment options].
AB  - Primary pulmonary hypertension (PPH) is a rare, progressive and life-threatening
      pulmonary vascular disease of unknown aetiology, which results in elevated
      pulmonary vascular resistance, pulmonary hypertension and eventually right
      ventricle failure. PPH occurs in all age groups, but most frequently in women
      aged 20-30 years old. The mean survival after the onset of symptoms is 2-3 years.
      Although the disease remains incurable at present, major advances in treatment
      options have been made during the last 10 years. This had led to a considerable
      improvement in extended survival and the quality of life in a substantial number
      of PPH patients. At present the most important treatment options include
      anticoagulants, calcium channel antagonists, chronic prostacyclin therapy (cost
      of this only reimbursed by health insurers in the Netherlands since 1999) and if
      needs be lung or heart-lung transplantation. Chronic continuous intravenous
      administration of epoprostenol is burdensome for the patient and requires
      adequate patient selection and a well-developed intramural and extramural
      infrastructure.

PMID- 11593787
TI  - [From gene to disease; risk factors for venous thrombosis: factor V Leiden and
      prothrombin 20210A].
AB  - Venous thromboembolic disease is an important clinical entity, in which both
      acquired and genetic risk factors play a causative role. Genetic factors which
      increase thrombotic risk consist of rare heterogeneous loss-of-function mutations
      in coagulation-inhibitory factors, such as antithrombin, protein S and C, and
      more common, but unique, gain-of-function mutations in coagulation factors V and
      II, so-called factor V-Leiden and prothrombin 20210A. The genetic defect
      underlying factor V-Leiden is a guanine (G) to adenine (A) mutation in the factor
      V gene, causing substitution of arginine at position 506 by glutamine, thereby
      providing resistance to proteolytic cleavage by activated protein C (APC). In the
      prothrombin 20210A allele a G to A mutation at nucleotide 20210 in the 3'
      untranslated region of the prothrombin gene is associated with increased
      prothrombin levels. The APC-resistance assay is used to screen for the presence
      of factor V-Leiden. Both factor V-Leiden and prothrombin 20210A are diagnosed by
      DNA analysis.

PMID- 11593788
TI  - [Diagnostic image (56) Barrett epithelium of esophagus in early carcinoma].
AB  - Barrett epithelium of the esophagus in a 63-year-old man with early carcinoma,
      detected at regular endoscopy.

PMID- 11593789
TI  - [Few ethnic differences in acute pediatric problems: 10 years of acute care in
      the Sophia Children's Hospital in Rotterdam]].
AB  - OBJECTIVE: To evaluate whether there are differences in acute general paediatric
      problems and their severity between children with different ethnic backgrounds.
      DESIGN: Descriptive. METHOD: The following information was registered for
      patients who visited the paediatric emergency department at the Sophia Children's
      Hospital in Rotterdam, the Netherlands (1988 through to 1997): demographics,
      reason for encounter, diagnoses, diagnostics performed and follow-up. Ethnicity
      was determined by patient's surname. Analyses were performed using the chi 2
      test, non-parametric Kruskal-Wallis test and multiple logistic regression.
      RESULTS: Fifty-one percent of all patients belonged to one of the ethnic minority
      groups. Infection-related problems were seen more often in Turkish (45%) and
      Moroccan (46%) children than in Dutch children (41%). Of those children with
      infection-related problems, the Turkish children were less likely to need X-rays
      (odds ratio: 0.73), laboratory diagnostics (0.72), an outpatient follow-up (0.79)
      or hospital admission (0.74). On the other hand, Moroccan paediatric patients
      were admitted slightly more frequently (to the intensive care department) and
      were more likely to have a lower respiratory tract infection (1.65). CONCLUSIONS:
      There were some differences between Dutch children and ethnic minorities in terms
      of the reasons for encounter and the severity of the problem. Compared with Dutch
      children, Turkish children presented with less severe infection-related problems,
      while Moroccan children had more severe infection problems.

PMID- 11593790
TI  - [Sarcoma of the thoracic wall following mastitis radiotherapy 38 years
      previously].
AB  - A 62-year-old woman presented with a feeling of pressure between her shoulder
      blades. Physical examination and laboratory test showed no abnormalities.
      Conventional X-ray of the thorax showed, by chance, a condensation of the second
      rib. CT scan showed a solitary lesion at the same location. Patient's history
      mentioned post-partum mastitis 38 years earlier, for which she was treated with X
      ray therapy of about 4 to 5 Gray in 1 fraction. A partial rib resection was
      performed prior to diagnosis. The histopathological diagnosis was stage IA
      chondrosarcoma. It was excised in toto and an uneventful disease course ensued.
      In the past, X-ray therapy was used for many different benign diseases. Many
      doctors nowadays are not aware of this. This case illustrates that radiotherapy
      for benign disease can give rise to post irradiation sarcomas. Long-term follow
      up of an irradiated region is essential for early diagnosis and may lead to
      higher cure rates.

PMID- 11593792
TI  - [Death certificates and the role of municipal coroner and the attending physician
      in natural and unnatural deaths in the Netherlands].

PMID- 11593791
TI  - [Candidate vaccine against urinary tract infections].
AB  - Urinary tract infections (UTIs) are an important medical problem for women. The
      most common uropathogen is Escherichia coli. The adherence of E. coli to the
      uroepithelium is mediated by the FimH adhesin, a minor component of type-1
      fimbriae. This is the initial step in the pathogenesis of UTIs. Recently, a
      candidate vaccine has been developed, based on this FimH adhesin. In animal
      studies and in a phase 1 study, this vaccine has proven to be both immunogenic
      and safe. In this era of increasing resistance to antibiotics, such a method of
      prevention is of high importance.

PMID- 11593793
TI  - [Visual impairment due to optic neuropathy in 2 patients on amiodarone, and
      ethambutol and isoniazide therapy, respectively].

PMID- 11593794
TI  - [Diagnostic steps in disk dislocations and other frequent illnesses of the
      temporomandibular joint].
AB  - Modern diagnosis of the temporomandibular joint (TMJ) consists of multiple steps,
      based on each other and amplifying one another. The first step is the clinical
      functional analysis, respecting general medical as well as specific dental
      aspects. If need arises electronic axiography, recording the movement of TMJ
      hingeaxis, is being added as well as occlusal analysis on mounted plaster casts.
      In case of open questions at this point of analysis, magnetresonance- and
      computer-tomographic imaging is brought in. The present paper is an overview
      describing the current step by step diagnosis of TMJ disorders, with special
      attention to luxation-reduction mechanism in the joints.

PMID- 11593795
TI  - [Diagnostic imaging of the normal anatomy of the temporomandibular joint].
AB  - Computed tomography (CT) and magnetic resonance imaging (MRI) are well
      established imaging modalities to examine the TMJ. MRI is superior to CT in
      delineating the morphological architecture of the TMJ, not only in cases of
      normal anatomy, inflammation or tumors, but also if dysfunction of the TMJ is
      present. This review article presents anatomy as well as imaging strategies of
      the TMJ.

PMID- 11593796
TI  - [Internal derangement of the temporomandibular joint].
AB  - Internal Derangement is one of the most common disorders of the Temporomandibular
      joint. It is defined as an abnormal anatomical relationship between the discus
      articularis and the other structures of the temporomandibular joint. More than
      2/3 of patients with clinical symptoms of the temporomandibular joint have an
      internal derangement. The most frequent finding in internal derangement is an
      anterior dislocation of the disc with reduction after mouth opening. In more
      severe cases a complete anterior dislocation is found without reduction of the
      disc. Internal derangement is a risk factor for developing osteoarthritis with
      remodeling of the condylus and the fossa mandibularis. The most important
      modalities of radiologic diagnosis are arthrography, CT and MRI. The diagnosis of
      craniofacial dysfunction has been improved dramatically by modern imaging
      techniques, which have become essential tools for primary diagnostic and
      evaluation after conservative or surgical therapy. MRI has become the gold
      standard.

PMID- 11593797
TI  - [Non-neoplastic arthropathies of the temporomandibular joint].
AB  - The pathologic conditions that involve the TMJ are similar to those conditions
      that involve other joints in the body. Therefore, many of the radiologic
      characteristics are also similar. Nevertheless, because of the complex structure
      and function of this small joint, it is essential to know the variety of diseases
      that can involve the temporomandibular joint. It is also important to understand
      that functionally both TMJ's act as a single unit and that any alteration in
      function caused by a pathologic process on one side may lead to dysfunction on
      the contralateral side. It is essential that the radiologist is familiar with the
      principles of TMJ function as well as TMJ pathology.

PMID- 11593798
TI  - [Traumatic temporomandibular joint injuries].
AB  - Injuries of the temporomandibular joint are mostly due to injuries or fractures
      of the mandibular condyle. Fractures of the skull base involving the
      temporomandibular joint are rare. Classification of fractures refers to their
      anatomical positions and the presence or absence of a luxation. Further, it is
      important whether the fracture is intra- or extra-capsular. The primary imaging
      method should be orthopantomography. As for therapy planning, especially surgery,
      also evaluation of soft tissue is necessary, computed tomography is the imaging
      method of choice. For diagnosis of complications or internal derangement of the
      temporomandibular joint, magnetic resonance imaging is to be recommended.

PMID- 11593799
TI  - [Neoplasms of the temporomandibular joint (TMJ). Diagnosis, differential
      diagnosis and intervention].
AB  - PURPOSE: To evaluate the effectiveness of diagnostic and interventional
      radiological techniques for neoplastic lesions of the temporomandibular joint
      (TMJ). MATERIAL AND METHODS: Modern diagnosis of the TMJ is based on the clinical
      use of conventional X-ray techniques, computed tomography (CT), magnetic
      resonance imaging (MRI) and interventional techniques like biopsies, vascular
      occlusion and ablation. RESULTS: Conventional X-ray still forms the basic
      diagnostic procedure applied in open and closed mouth position. CT improves the
      diagnostic information and serves as the standard diagnostical instrument for
      cartaliganeous or osseous neoplastic lesions. MRI evaluates soft tissue
      infiltration in multiplanar techniques and high spatial resolution.
      Interventional vascular and ablative techniques improve the treatment of
      neoplastic disorders. CONCLUSION: Radiological diagnostic procedures are
      essentials for the diagnosis and intervention of neoplastic lesions of the
      temporomandibular joint.

PMID- 11593800
TI  - [Postoperative temporomandibular joint diagnosis].
AB  - Postoperative management of patients suffering from symptoms of the
      temporomandibular joint does not differ considerably from the one of preoperative
      examination protocols. Knowledge of previous surgery helps to plan patient work
      up and to interpret normal postoperative findings (eminectomy, discectomy,
      susceptibility artefacts from metallic residues...) and typical complications
      (intraarticular loose bodies, dislocations, avascular necrosis, foreign body
      granulomatous reactions) appropriately.

PMID- 11593801
TI  - [Treatment strategy in functional temporomandibular joint changes].
AB  - In the management of functional disturbances of the stomatognathic system
      symptomatic and causal therapeutic methods can be distinguished. Symptomatic
      therapy encompasses medication, physical methods (heat, cold, radiation, TENS) in
      combination with physiotherapy and emergency splint. After one or two weeks of
      symptomatic therapy the patient should be free of pain allowing precise
      diagnostic procedures followed by causal therapy managing muscular problems,
      joint pathology and occlusal disturbances. Splint therapy is used to establish a
      therapeutic joint position according to articulator mounting. After splint
      therapy prosthodontic and/or orthodontic treatment is needed to restore
      occlusion. Interdisciplinary management in the therapy of functional disturbances
      of the stomatognathic system is of utmost importance due to the relationship
      between chewing muscles, neck muscles and body posture. In addition to splint
      therapy, physiotherapy, logopedic therapy, myofunctional therapy, psychologic and
      psychiatric intervention is performed.

PMID- 11593802
TI  - [Recurrent epigastric pain with weight loss and loss of appetite].

PMID- 11593803
TI  - [Ultrasound anatomy of the shoulder joint during the growth period].
AB  - AIM OF STUDY: It is the aim of this investigation to describe the normal
      ultrasonographical appearance of the glenohumeral joint in childhood. METHODS:
      Ultrasound investigation was performed in 20 healthy children aged between 6
      weeks and 19 years (median: 6 years) using 12 MHz linear probes. A dynamic
      examination of both shoulders was carried out. Probe positions according to
      standard planes were used, and attention was paid to visualise the growth
      regions. RESULTS: Ultrasound images of the periarticular soft tissue in children
      do not differ markedly from those in adults. However, there are basic structural
      differences of the epiphyseal and apophyseal regions. In the newborn period the
      proximal humeral epiphysis mainly consists of cartilage and changes to the adult
      shape after the appearance of three secondary ossification centers and growth
      plates. Interestingly, the chondral buds of the acromion or coracoid process
      offer additional imaging facilities for ultrasound examination in children.
      CONCLUSIONS: Ultrasound examination of the glenohumeral joint in children offers
      a more precise evaluation when compared to adults, due to the presence of
      additional ultrasonographical "windows" and depiction of parts of the humeral
      epiphysis. This imaging technique is well tolerated by children.

PMID- 11593804
TI  - [Diagnosis of bone metastasis with whole body MRI?].

PMID- 11593805
TI  - [The endoleak problem in endoluminal therapy].
AB  - Endovascular treatment of aortic aneurysms with stent grafts was performed
      increasingly in recent years. The most frequent complication after endovascular
      therapy of aortic aneurysms is an endoleak. In case of a persistent endoleak,
      diameter of the aneurysm is increasing with a high risk of aneurysm ruptur.
      Diagnostic tools are spiral computed tomography and angiography. Spiral computed
      tomography is the most sensitive method for the diagnosis of an endoleak ad
      should be performed with a biphasic acquisition. In- and outflow of sidebranches
      can be identified correctly with selective angiography in 86%. Perigraft
      endoleaks should be treated in any case. Patent side branches generally are
      observed over a period of 6 months. After 6 months approximately half of these
      endoleaks are thrombosed. Is there an increasing of the diameter of the aneurysm
      or any changing in the morphology of the aneurysm there is an indication for
      embolisation of these sidebranches of the aneurysmal sac. Preinterventional
      embolisation of patent sidebranches is under discussion. Type I endoleaks can be
      managed by additional stent-graft implantation or coil embolisation. In case of
      type II endoleaks in- ad outflow vessels should be embolised with coils. Therapy
      of type III endoleak is performed mostly by additional stent-graft placement. The
      total incidence of secondary interventions in the Eurostar-study was nearly 10%
      per year.

PMID- 11593806
TI  - [Radiologic diagnosis of the gallbladder and bile ducts. 2: Extra- and
      intrahepatic obstruction, value of diagnostic methods].

PMID- 11593807
TI  - [Problems of dental diseases among young residents of the Archangelsk region].
AB  - Dental examinations (according to WHO methods) were carried out in 447 youths
      aged 18-19 years, residents of Northern Russia, in Archangelsk before army
      service, and 500 students of Northern Medical University. Dental health of young
      people was characterized by high incidence and prevalence of caries (9.4.31%, CDL
      = 5.94), periodontal diseases, maxillodental abnormalities (72.18%), high
      percentage of lost teeth (8.75) in the CDL structure, poor oral hygiene (OHI-S
      index 3.68), and high level of need in all types of dental care, this
      demonstrating poor organization of health improving measures for young people
      before military service. Poor dental health in young people aged 18-19 years is
      one of the causes making them unfit for army service or fit with limitations (47
      subjects for categories C, D in 1996-1998, 100-198 subjects annually for category
      B).

PMID- 11593808
TI  - [Incidence of diseases with temporary disability among dentists].
AB  - Incidence of diseases involving temporary disability among dentists in Tver is
      81.2 cases and 939.2 days per 100 workers; according to the data of sociological
      interviews (with consideration for chronic diseases and self-treatment cases over
      3 years), it is 120.5 cases per 100 workers. The percentage of dentists with
      chronic diseases is 69.9, which is lower than recorded in medical files (21.4%).
      This indicates a high percentage of nonrecorded diseases which are self-treated.

PMID- 11593809
TI  - [Attitude to health in patients with cardiovascular disability].

PMID- 11593810
TI  - [On integral criterion of public health].

PMID- 11593811
TI  - [Methodological approaches to the reform of the municipal public health system].

PMID- 11593812
TI  - [Public health reform in the Novgorod region: main results and prospects].

PMID- 11593813
TI  - [Economic efficiency of computer monitoring of health].
AB  - Presents the method of computer monitoring of health, based on utilization of
      modern information technologies in public health. The method helps organize
      preventive activities of an outpatient clinic at a high level and essentially
      decrease the time and money loss. Efficiency of such preventive measures,
      increased number of computer and Internet users suggests that such methods are
      promising and further studies in this field are needed.

PMID- 11593814
TI  - [Public health systems and methods of their financing].
AB  - A correlation between type of the state as regards public consciousness
      (authoritarian, liberal, democratic) and type of public health is disclosed. The
      type of public health determines the ways of its financing (centralized
      management, tariff regulation, and free prices) and forms of regulation of
      financial flows in public health.

PMID- 11593815
TI  - [Integral evaluation of socio-hygienic status of preschool children].

PMID- 11593817
TI  - [Complex of measures aimed at prevention of breast cancer].
AB  - Comprehensive approach to prevention, detection, and treatment of pretumor
      diseases of mammary glands was practiced in a region of a city with 52,000 female
      population during 15 years. Local therapists and gynecologists were involved in
      the work, which resulted in 2.5 time decrease in the incidence of edematous
      infiltrative breast cancers, increase in the number of older patients, and
      decrease of mortality from 42.7 to 24.4%.

PMID- 11593816
TI  - [Organizational forms of primary health care in Uzbekistan].
AB  - Some management aspects in improvement of primary health care in Uzbekistan are
      analyzed. The scope and types of activities of primary health centers in the
      rural regions and their role in organization of medical care of the rural
      population are discussed. Data on morbidity structure is analyzed by the rate of
      consultations in the rural health centers. Municipal (makhalla) medical centers
      were set up in cities for making basic medical care easier available for city
      (makhalla) residents; a system of urgent medical care has been created.
      Republican Research Center of Urgent Medical Care has been created in Uzbekistan
      with branches in all regions and in Karakalpakstan Republic and departments of
      urgent medical care in all central regional and city hospital with ambulance;
      they are financed completely from the state budget.

PMID- 11593818
TI  - [Medical and organizational aspects of medical counseling to would-be medical
      students at institutions of higher learning].
AB  - Modern higher school requires great physical, intellectual, and psychoemotional
      efforts from students. Adolescent health is a most important prerequisite for
      higher education and work in accordance with the specialization acquired at
      higher school. Therefore, the priority task in students' health preservation
      today is improvement of the continuity and quality of physicians' activities as
      regards medical vocational counselling of adolescent children and young people.

PMID- 11593819
TI  - [Training of the modern clinical physician and public health managers].
AB  - Arguments of Russian and foreign specialists that the activities of a modern
      physician are based on knowledge, habits and skills of a clinician and
      experience, habits and skills of a manager are discussed. The author proves that
      managing skills acquired by physician as an element in his/her professional
      activity through experience should be supplemented by knowledge of modern theory
      and practice of management. In the twenty-first century modern theory and
      practice of management should become a universal basis and element of
      professional cooperation of clinical physicians, physicians working in
      administration of public health organs and institutions, and public health
      economists.

PMID- 11593820
TI  - [Experience gained in the establishing of the regional disease control system].

PMID- 11593821
TI  - [Experience in accreditation of medical facilities in the Altai region].

PMID- 11593822
TI  - [Organization of medico-social care of elderly and senile individuals].

PMID- 11593823
TI  - [Intentions of the authors of The 1835 Code and realities of the curriculum of
      The Medical Department of Moscow University in 1837-45].

PMID- 11593824
TI  - [Health status and delivery of medical services among various groups of the
      population in the republic of Sakha (Yakutia)].
AB  - Disease prevalence is analyzed on the basis of questionnaires distributed among
      the population of Sakha (Yakutia) Republic. The following population groups were
      distinguished: aborigines (Yakuts and Russians) and newcomers, each with specific
      health status. The worst health characteristics were detected in Russians and
      newcomers. These health parameters form as a result of difficulties in life
      support in comparison with other population groups; medical care system requires
      special attention as a factor promoting health formation.

PMID- 11593825
TI  - [Medical institutions at orthodox convents as contribution to public health in
      pre-revolutionary Russia].

PMID- 11593826
TI  - [Medical information in the "Florine Economy"].

PMID- 11593827
TI  - Construction-related nosocomial infections in patients in health care facilities.
      Decreasing the risk of Aspergillus, Legionella and other infections.
AB  - Construction and renovation projects in health care facilities are a risk for
      certain patients, particularly those who are immunocompromised. A proactive
      approach must be taken to limit construction-related nosocomial infections. This
      requires having a multidisciplinary team, supported by administration, to plan
      and implement preventive measures throughout the duration of the construction
      project. The ICP should be an active team member in all phases of the project.
      The ICP plays a major role by providing education to personnel; ensuring that
      preventive measures are identified, initiated, and maintained; and carrying out
      surveillance for infections in patients. By ensuring that the appropriate
      preventive measures are in place and clear lines of communication exist among the
      personnel, patient safety will be enhanced.

PMID- 11593828
TI  - Continuity of care--going out of style?

PMID- 11593829
TI  - Between the hammer and the anvil?

PMID- 11593830
TI  - Proton pump inhibitors: perspectives of patients and their GPs.
AB  - BACKGROUND: There is growing concern with the rapid increase in prescribing
      proton pump inhibitor drugs (PPIs) for a variety of gastrointestinal disorders,
      and the escalating costs associated with this trend. Explanations have included
      that general practitioners (GPs) prescribe PPIs inappropriately and that patients
      demand PPIs and use them as a way of avoiding having to make lifestyle changes.
      AIM: To compare the perspectives of GPs and their patients on the need for PPIs,
      to examine the pressure to prescribe, and to examine the effect of PPIs on
      lifestyle. DESIGN OF STUDY: Qualitative comparative study based on semi
      structured interviews. SETTING: Twenty-six GPs in seven practices in the West
      Midlands and 82 of their patients on repeat prescriptions for PPIs. METHOD:
      Interviews were conducted covering a wide range of topics, including: experience,
      cause, course, and outcome of stomach problems; effectiveness of PPIs; and role
      of lifestyle in controlling symptoms. The transcripts were studied repeatedly to
      look for the occurrence and distribution of material relating to these issues, as
      well as other responder-driven issues. Codebooks were devised to enable a simple
      categorisation and systematic comparison of cases. RESULTS: GPs and patients
      agreed about the severity and unpleasantness of stomach symptoms for which PPIs
      were prescribed. While GPs and patients regarded PPIs as a very effective
      treatment, GPs rated their efficacy more highly than patients. Half of the GP
      interviews reproduced the stereotype of the demanding patient and of patients
      using PPIs to support unhealthy lifestyles. There was little evidence from
      patient interviews to support either stereotype. Doctors underestimated patient
      concerns about side-effects, safety, and long-term use of PPIs, and the
      willingness of patients to achieve the minimum effective dose by experimenting
      with their treatment. GPs felt that the pressure to prescribe PPIs was outweighed
      by the pressure not to prescribe, and most GPs had responded to the call to cut
      the prescribing of PPIs. Different strategies were employed to cut prescribing,
      including the wholesale switching of patients on a treatment dose of one brand of
      PPI to a maintenance dose of a cheaper brand of PPI, known as 'double switching'.
      CONCLUSION: The stereotypes of 'profligate prescriber', 'demanding patient', and
      'adverse lifestyle', as explanations for the increase in the prescribing of PPIs,
      were not upheld. The stereotype of patients demanding PPIs may arise from GPs'
      internal pressure to prescribe being externalised onto patients. The extent to
      which health behaviour contributes to gastric disorders needs to be established
      empirically. Labelling PPI patients as having a poor lifestyle may be used as a
      means of reducing legitimate need for PPIs. Current policy relating to switching
      of dose and brand of PPI should be reviewed.

PMID- 11593831
TI  - An exploration of the value of the personal doctor-patient relationship in
      general practice.
AB  - BACKGROUND: Within the context of general practice, continuity of care creates an
      opportunity for a personal doctor-patient relationship to develop which has been
      associated with significant benefits for patients and general practitioners
      (GPs). Continuity of care is, however, threatened by trends in the organisational
      development of primary health care in the United Kingdom and its intrinsic role
      within general practice is currently the subject of debate. AIMS: To determine
      how many patients report having a personal doctor and when this is most valued,
      to compare the value of a personal doctor-patient relationship with that of
      convenience, and to relate these findings to a range of patient, GP, and practice
      variables. DESIGN OF STUDY: Cross sectional postal questionnaire study. SETTING:
      Nine hundred and ninety-six randomly selected adult patients from a stratified
      random sample of 18 practices and 284 GP principals in Oxfordshire. METHOD:
      Qualitative interviews with patients and GPs were conducted and used to derive a
      parallel patient and GP questionnaire. Each patient (100 from each practice) was
      invited to complete a questionnaire to evaluate their experience and views
      concerning personal care. All GP principals currently practising in Oxfordshire
      were sent a similar questionnaire, which also included demographic variables.
      RESULTS: Overall, 75% of patients reported having at least one personal GP. The
      number of patients reporting a personal GP in each practice varied from 53% to
      92%. Having a personal doctor-patient relationship was highly valued by patients
      and GPs, in particular for more serious, psychological and family issues when 77
      88% of patients and 80-98% of GPs valued a personal relationship more than a
      convenient appointment. For minor illness it had much less value. CONCLUSIONS:
      Patients and GPs particularly value a personal doctor-patient relationship for
      more serious or for psychological problems. Whether a patient has a personal GP
      is associated with their perception of its importance and with factors which
      create an opportunity for a relationship to evolve.

PMID- 11593832
TI  - A qualitative study of older people's views of out-of-hours services.
AB  - BACKGROUND: Out-of-hours primary care services continues to change with the
      growth of general practitioner (GP) co-operatives and the more recent development
      of NHS Direct. While older people are more likely to have increased needs for
      such services, evidence suggests that they are reluctant users of GP out-of-hours
      services. AIM: To explore older people's experiences and perceptions of different
      models of general practice out-of-hours services. DESIGN OF STUDY: Focus group
      methodology, with qualitative data analysis undertaken using a grounded theory
      (Framework) approach. SETTING: Thirty people aged between 65 and 81 years old
      from community groups based in south east London. METHOD: Four focus groups were
      held, each with between five and 12 participants. Each focus group session lasted
      90 minutes and was audiotape-recorded with the permission of the participants.
      The tapes were transcribed verbatim. RESULTS: Two related themes were identified.
      First, attitudes to health and healthcare professionals with reference to the use
      of health services prior to the establishment of the NHS, a stoical attitude
      towards health, and not wanting to make excessive demands on health services.
      Second, the experience of out-of-hours care and the perceived barriers to its
      use, including the use of the telephone and travelling at night. Participants
      preferred contact with a familiar doctor and were distrustful of telephone
      advice, particularly from nurses. CONCLUSIONS: Older people appear reluctant to
      make use of out-of-hours services and are critical of the trend away from out-of
      hours care being delivered by a familiar GP. With increasing numbers of older
      people in the population it is important to consider steps to address their
      reluctance to use out-of-hours and telephone advice services, particularly those
      based around less personal models of care.

PMID- 11593833
TI  - How general practice patients with emotional problems presenting with somatic or
      psychological symptoms explain their improvement.
AB  - BACKGROUND: The emotional problems of patients presenting only somatic symptoms
      are frequently not detected by general practitioners (GPs), yet clinical outcomes
      have often been found to be no different from emotional problems directly
      presented. AIM: To compare clinical outcomes and attributions for improvement of
      patients with emotional problems presenting only somatic symptoms to GPs, with
      patients directly presenting emotional problems. DESIGN OF STUDY: Survey of
      patients with General Health Questionnaire (GHQ) scores in the symptomatic range,
      with follow-up after three months of a repeat GHQ and a questionnaire of
      patients' attributions for improvement. SETTING: A sample of 152 adult patients
      from nine general practices in North and East London. METHOD: Consecutive
      patients were invited to complete an adapted GHQ prior to their consultation. The
      consultations were audiotaped and coded to indicate the extent to which
      psychological discussion took place, as against discussion of other issues. The
      GPs recorded whether they considered each patient to be emotionally disturbed or
      psychiatrically ill at the time of the consultation, to assess GP detection of
      emotional disturbance. To form the initial sample, interviews were conducted one
      to five days after the consultation with patients who intended to present with
      either psychological or somatic problems, with a follow-up questionnaire after
      three months. RESULTS: A total of 106 patients provided follow-up information, of
      whom 57 presented psychological problems directly at initial consultation and 49
      presented only somatic symptoms. There were no differences in clinical outcome at
      three months between the two groups. Somatic presenters who improved were more
      likely than psychological presenters to attribute improvement to change in their
      physical health (68% versus 31%) while psychological presenters were more likely
      to attribute improvement to the GP's listening and counselling in the
      consultation (44% versus 18%). Other attributions for improvement, such as
      passage of time, change in life circumstances, support of family and friends,
      medication, and 'working through problems myself', were equally common in both
      groups. CONCLUSIONS: Patients with emotional problems presenting only somatic
      symptoms have equivalent clinical outcomes to patients presenting psychological
      problems directly, but are more likely to attribute emotional improvements to
      change in their physical health. For some such emotionally disturbed patients it
      may be sufficient for GPs to treat the physical health problems and to reassure
      the patient, without attempting to treat the underlying emotional disturbance.

PMID- 11593834
TI  - Perspectives of people with enduring mental ill health from a community-based
      qualitative study.
AB  - BACKGROUND: The views of people with enduring mental ill health have received
      limited exploration. Existing work has largely focused on patients in specialist
      mental health settings, rather than on a wider range of patients in the
      community. AIM: To explore experiences and perceptions of health care of people
      with enduring mental ill health. DESIGN OF STUDY: A community-based qualitative
      study using theoretical sampling, in-depth interviews, and grounded methodology.
      SETTING: A total of 34 responders registered with four general practices, serving
      five wards with a mean Townsend Deprivation Score of 7.75. METHOD: Subjects were
      chosen using a theoretical sampling framework and they participated in one-to-one
      interviews which were audiotaped. Themes were identified and developed by reading
      transcripts, then they were further refined and classified manually by open
      coding into key categories using a grounded approach. RESULTS: The primary goal
      of the responders was to enhance, sustain, and take control of their mental
      health. The building of positive therapeutic relationships with professionals
      based upon effective communication, trust, and continuity were important to
      achieving this aim. However, the settings in which their health care took place
      could affect responders' attempts to deal with social stigma. Experiences of
      social isolation, socioeconomic privation, and stigmatisation were often
      pervasive. These compromised responders' opportunities and their capacity to
      enhance their mental health, compounding their illness and marginalisation.
      CONCLUSIONS: This study shows the potential of health professionals to empower
      people with enduring mental ill health, by attending to the quality of
      communication and continuity of care they provide and to where this takes place.
      It further underlines a need to address the social stigma and exclusion this
      group experiences.

PMID- 11593835
TI  - Randomised controlled trial of tailored strategies to implement guidelines for
      the management of patients with depression in general practice.
AB  - BACKGROUND: Various methods are available for implementing change in the clinical
      behaviour of general practitioners (GPs). Although passive dissemination of
      information is generally ineffective, other methods can be variably effective.
      Few studies have investigated the impact of tailored methods. AIM: To determine
      whether methods tailored to overcome obstacles to change using psychological
      theories are more effective than dissemination alone in the implementation of
      guidelines for depression among GPs. DESIGN OF STUDY: Randomised controlled
      trial. SETTING: Sixty general practices in England; 30 GPs in the control group,
      34 in the intervention group. METHOD: Practitioners identified patients
      presenting with depression before and after the implementation of guidelines
      (control group n = 192 in the first data collection, n = 181 in the second;
      intervention group n = 210 in the first data collection and n = 197 in the
      second). The main outcome measures were: record of adherence to guideline
      recommendations in clinical records; proportion of patients with Beck Depression
      Inventory (BDI) score less than 11 at 16 weeks after diagnosis. RESULTS: In
      comparison with the control group, in the group of GPs receiving tailored
      implementation, there were increases in the proportions of patients assessed for
      suicide risk. In the intervention group, the proportion of patients with BDI
      scores of less than 11 at 16 weeks increased. CONCLUSION: Obstacles to
      implementation can be identified and strategies tailored to address them. The
      findings indicate a new approach for research to understand and develop methods
      of implementation.

PMID- 11593836
TI  - Aspirin use for the prevention of cardiovascular disease: the British Women's
      Heart and Health Study.
AB  - Low dose aspirin is effective, safe, and economical in the secondary prevention
      of cardiovascular disease. We have found that only one-third of post-menopausal
      women with cardiovascular disease are using aspirin and that the majority of
      women who are using aspirin are doing so for primary prevention. Improvements in
      this area of medical practice are both necessary and feasible.

PMID- 11593837
TI  - Telerheumatology--diagnostic accuracy and acceptability to patient, specialist,
      and general practitioner.
AB  - This study examines the diagnostic accuracy and acceptability of telemedicine in
      the field of rheumatology. One hundred patients had a telephone and televisual
      consultation and the results were compared with a face-to-face consultation.
      While the telephone consultations were often unsatisfactory, the televisual
      consultations were highly accurate (97%) and acceptable to patients, general
      practitioners, and specialists.

PMID- 11593838
TI  - A healthy disposition? The use and limitations of the characteristics approach to
      general practice research.
AB  - A range of easily identifiable characteristics is often used by researchers and
      general practitioners to categorise primary care practices. In the United
      Kingdom, for example, practices can be defined as dispensing, single-handed or
      training. The availability of routinely collected data has led to a growing
      research literature that links practice characteristics to their workload,
      performance and costs. This paper examines the use and limitations of this
      'characteristics approach' and argues that this type of research is often
      undertaken because it is easy to perform rather than because it is the most
      appropriate way to study primary care. Using this approach may lead to failure to
      do the following: to account for the environmental factors that determine the
      effects particular characteristics manifest; to identify the true relationships
      between the observed characteristics; to control for changes in the effects of
      characteristics over time; to differentiate between the behaviour of individual
      members of a group with the same characteristic and that of the group as a whole;
      to assign the correct causality to relationships between practice
      characteristics, workloads, performance, and costs. The characteristics approach
      should be used with great caution by general practice researchers.

PMID- 11593839
TI  - Health inequalities and deprivation.

PMID- 11593841
TI  - Health inequalities and deprivation.

PMID- 11593840
TI  - Health inequalities and deprivation.

PMID- 11593842
TI  - Health inequalities and deprivation.

PMID- 11593843
TI  - Health inequalities and deprivation.

PMID- 11593844
TI  - Pitfalls of 'inert' ingredients.

PMID- 11593845
TI  - Pitfalls of 'inert' ingredients.

PMID- 11593847
TI  - Frequent attenders in general practice.

PMID- 11593846
TI  - Frequent attenders in general practice.

PMID- 11593848
TI  - Patients and doctors with hearing difficulties.

PMID- 11593850
TI  - Chronic fatigue syndrome.

PMID- 11593849
TI  - Chlamydia trachomatis: opportunistic screening in primary care.

PMID- 11593851
TI  - Recruitment of practices to primary care trials.

PMID- 11593852
TI  - Culture and history in psychiatric diagnosis and practice.
AB  - A brief review of the history of Western psychiatry underscores how happenings in
      Anglo European societies during the early modern and modern era impacted on
      regional populations in the midst of profound demographic, social and political
      economic change. Such factors along with cultural conventions created an amalgam
      of behavior problems: social responses to these under the aegis administrative
      bodies gave rise to the discipline and profession of psychiatry. Central tenets
      that we take for granted as facts about psychiatric disorders (e.g., their
      manifestations, natural history, diagnosis) were shaped by historical and
      cultural influences. Psychiatry may outline a science of the psyche and its
      disturbances but it also reflects a cultural interpretation about personal
      experience, responsibility, social behavior, and the requirements for social
      order. The cultural character of the psychiatric enterprise itself, just as much
      as the characteristics of its disorders, constitute the subject matter of
      cultural psychiatry. Events during the late eighteenth and nineteenth centuries
      in Anglo European societies gave rise to psychiatry. First, there took place the
      differentiation of psychiatric disorders from the pool of human social and
      behavior problems. Second, and in relation to this, a segment of the medical
      profession was accorded (or appropriated) a social mandate and acquired an
      obligation to treat victims of mental disorders. The historical sociology of
      psychiatry constitutes one aspect of cultural psychiatry. The second covers
      developments during the latter part of the twentieth century. At this juncture,
      psychiatry became the target of labeling theorists in sociology, cultural
      relativists in anthropology, antipsychiatrists from within the discipline itself,
      and revisionist and critical historians of psychiatry. An outgrowth of this is
      the perspective that underscores the important role played by values, ideas, and
      world-views in how individuals experience and carry out their lives, phenomena
      that are critical to the expression, interpretation, diagnosis, and treatment of
      psychiatric disorders. That the science and practice of modern psychiatry
      incorporate an ethnocentric, Anglo European bias or slant on psychopathology is
      an integral assumption of cultural psychiatry. By describing how other non
      Western systems of psychiatry have operated, for example, their theories and
      practices, one gains a further appreciation of the important role of culture in
      shaping Western psychiatry. This is taken up in an article by Fabrega elsewhere
      in this issue where concepts and practices of traditional Chinese and Indian
      medicine that pertain to mental health and illness are reviewed.

PMID- 11593853
TI  - Culture in DSM-IV, ICD-10, and evolving diagnostic systems.
AB  - The past decade has shown interesting attempts to articulate the cultural
      framework of psychiatric diagnosis. Most distinctive in this regard has been the
      culture presence in DSM-IV. Less substantial concerning culture has been the core
      ICD-10. Of high cultural interest are the national and international adaptations
      of ICD-10 because of their aim at articulating universality with local realities
      and needs. The WPA International Guidelines for Diagnostic Assessment exhibits an
      innovative diagnostic system that combines standardized multiaxial and
      personalized idiographic formulations with pointed attention to culture
      considerations. Finally, this article outlines some culture-informed
      recommendations for the development of future diagnostic systems.

PMID- 11593854
TI  - From diversity to unity. The classification of mental disorders in 21st-century
      China.
AB  - Psychiatric disease constructs represent social constructs and genuine states of
      distress that have biopsychosocial sources. As such, they have social uses
      peculiar to the social groups in which they are created and legitimized. This is
      as true in the United States as in the rest of the world. The DSM schema, for
      instance, is so organized that every possible mental condition is listed as a
      disease to legitimate remuneration to practitioners from private medical
      insurance and government programs. This particular social use may be irrelevant
      to other societies where health care is financed differently. The CCMD-3 system
      represents an attempt at global unification and preservation of features that are
      salient for local application. Compared with its previous editions, noticeable
      changes have been made to render it in tune with international usage. This
      remarkable speed of adaptation speaks to the global flows of information
      technology and China's openness under rapid economic reform. It also demonstrates
      that the middle-aged cohort of more pragmatic Chinese psychiatric leaders who
      headed the CCMD-3 task force are now less vulnerable to the domination of the
      most senior generation of Chinese psychiatrists. Having been trained in the
      Russian system of psychiatry and gone through the various periods of national
      shame that traumatized China, they used to be very cautious about adopting
      foreign technology in general. This is why much less harmonization with the ICD
      10 occurred with the CCMD-2-R, when the responsible task force was, for better or
      worse, dominated by these senior psychiatrists. Nonetheless, as Stengel and
      Sartorius remarked, an international classification must not aim to oust or
      replace regional classifications that serve valuable functions in the local
      contexts. No single classificatory system, Kirmayer submits, will suffice for all
      purposes--the correct diagnostic scheme is the one that accomplishes its explicit
      pragmatic aim by addressing the relevant level of description. The particular
      additions (e.g., travelling psychosis, culture-related mental disorders),
      deletions (e.g., depressive neurosis, pathologic gambling, avoidant and
      borderline personality disorders), retentions (e.g., unipolar mania, neurosis,
      hysteria, homosexuality), and epistemologic variations (e.g., somatoform
      disorder, neurasthenia) of diagnostic categories reflect exactly this
      simultaneous need to globalize and to take account of the changing reality of
      illness in contemporary China. Stengel advised that "no psychiatric
      classification can help being partly etiological and partly symptomatological,
      because these are the criteria by which psychiatrists distinguish mental
      disorders from each other." To an extent, the CCMD-3 is a critique of certain
      nosologic assumptions of Western psychiatry, such as the feasibility of a neo
      Kraepelinian taxonomy grounded exclusively in symptomatology across all
      diagnostic categories, and the validity of syndromic architectures based on a
      firm adherence to the mind-body dichotomy. From this angle of vision, local
      systems of classification such as the CCMD-3 may offer an opportunity for needed
      reflections by North American psychiatrists who have simply taken the DSM-IV
      schema for granted. Sartorius reckoned that a classification is a way of seeing
      the world at a point in time. A deep study of the CCMD-3 is thus an avenue for
      achieving an understanding of the contemporary Chinese mind and the social
      realities in China. The remarkable diversity of China at present, namely, a
      Communist Party dominated state socialist political structure but the most
      rapidly growing capitalist economy in the world, guarantees that Chinese people's
      social and moral experience of illness will continue to change. The study of such
      culture-specific categories as travelling psychosis, neurasthenia, qigong-induced
      mental disorder, and dysfunctional homosexuality sheds light on the larger
      sociomoral processes and destabilizing changes in subjectivity that are occurring
      in this most populous country in the world.

PMID- 11593855
TI  - The Latin American guide for psychiatric diagnosis. A cultural overview.
AB  - The ICD-10 Classification of Mental and Behavioral Disorders is being accepted by
      most countries and by the World Psychiatric Association as the international
      standard in the field for statistical reporting and for clinical care and
      research. Emerging now, however, is the need to harmonize international
      communication with recognition of cultural diversity and specific local
      requirements. Latin American psychiatrists hold a long-standing commitment to the
      formulation of a reliable and valid diagnostic system in international
      psychiatry. Examples of important Latin American contributions include the
      pioneering use of explicit operational criteria in diagnostic methodology by
      Horwitz and Marconi in Chile, and the proposal of a multiaxial diagnostic
      formulation by Leme-Lopes in Brazil. In recent times, two main Latin American
      efforts at developing diagnostic adaptations to the international classification
      in psychiatry have emerged. One is the Cuban Glossary of Psychiatry, already in
      its third edition, and the second is a more ambitious project to develop the
      Latin American Guide for Psychiatric Diagnosis (GLADP). Departing from the
      experience gained by the Cuban psychiatry and keeping ICD-10 as the basis for
      nosological organization of mental disorders, the GLADP is being developed with
      the contributions of psychiatrists and other mental health professionals from
      most countries in Latin America. The GLADP comprises 4 parts: (I) historical and
      cultural framework of Latin American psychiatry; (II) a comprehensive diagnostic
      process and formulation, (III) psychiatric nosology (including ICD-10 major
      classes of disorders and Latin American cultural syndromes); and (IV) appendixes
      (including, a lexicologic glossary, concepts and proposals for future study, and
      bibliography). This is an overview of the basic principles and dimensions for
      psychiatric diagnosis in Latin America, with an emphasis on its cultural
      framework.

PMID- 11593856
TI  - Culture and schizophrenia and other psychotic disorders.
AB  - The comparative study of schizophrenia and related disorders across cultures has
      come a long way since Kraepelin advocated its cause, following his trip to Java
      at the beginning of the last century. The principal development since then has
      been the burgeoning of interest in the field, culminating in innovative and
      ambitious international collaborative research by the WHO. Despite reservations
      about covert ideology or about the more overt methodologic difficulties, the
      balance of evidence from these and similar studies suggests that: It is feasible
      to conduct such research despite the numerous hazards. There is a certain
      uniformity to the way schizophrenia presents globally; there are equally
      significant cultural differences. The outcome of schizophrenia appears to be
      better in developing, than developed cultures; reasons for this are far from
      clear, nevertheless, it can be safely assumed that culturally-determined
      processes, whether social or environmental, are partly responsible. Overall, the
      study of schizophrenia in different cultures has proved useful in establishing
      the pancultural and the culture-specific properties of this and related
      disorders.

PMID- 11593857
TI  - Affective disorders in cultural context.
AB  - This article reviews epidemiologic and ethnographic evidence for the cultural
      shaping of the causes, symptomatology, and course of affective disorders. Cross
      cultural research demonstrates much overlap of depression with anxiety,
      somatoform, and dissociative disorders, raising questions about the universality
      of the prototypical representation of depression in North American psychiatry.
      Culture-specific symptoms may lead to under-recognition or misidentification of
      syndromes of mania and depression in many ethnocultural groups. Cultural idioms
      of distress may employ symptoms related to affective disorders to express
      sentiments and perceptions that do not in themselves indicate psychopathology.
      Socially mediated cognition about the self and specific modes of interpersonal
      interaction influence the course of depression. This article discusses some
      implications of these findings for the recognition and treatment of affective
      disorders among culturally diverse populations in primary care and mental health
      care settings.

PMID- 11593858
TI  - Culture and substance abuse.
AB  - Although inhaling is commonly thought of as a novel form of drug use, it has been
      customary for centuries with finely ground tobacco or with a wide variety of
      hallucinogenic powdered plant derivatives in tropical South America (de Rios).
      Nose pipes facilitate snuffing in some cultures, and in others, drugs are blown,
      by turn, through tubes into the nostrils of companions. Pictorial evidence
      illustrates the use of enemas as an alternative means of ingesting drugs,
      especially among a few pre-Columbian Indian populations in Central and South
      America. In light of the rapidity of absorption from the bowels to the
      bloodstream, one may wonder why it has been so little used (or at least reported)
      in recent years. Even within the modern, urban United States, the verbs drink,
      smoke, and eat have variously been used to characterize variant means of
      ingesting drugs. Dire predictions about a generation of hopeless "crack babies"
      have not been confirmed, but differential treatment and punishment of users has
      resulted in the unjust imprisonment of many more blacks and for longer periods,
      even though whites are more numerous among drug users.

PMID- 11593859
TI  - Culture and child psychiatric disorders. A Nigerian perspective.
AB  - This article has reviewed some critical aspects of the sociocultural framework
      informing the life and health of Nigerian children and adolescents. Expectations
      on individual and social functioning and on the role of extended families have
      been highlighted. Cultural influences on the manner and circumstances of
      assessing health problems and on development, presentation, and course of child
      psychiatric disorders have been outlined. Approaches and strategies for
      therapeutic invention have been summarized, with attention given to primary,
      secondary, and tertiary prevention, and to the organization of therapy and
      counseling aimed at satisfying goals and needs of children and adolescents in
      Nigeria. Even just adequate epidemiologic data, ordinarily considered to be the
      hallmark of evidence-based scientific statements on child and adolescent
      psychiatric disorders, are infrequent in Africa in general, and in Nigeria in
      particular, because of sociopolitical and dire economic factors. The latter
      affects the availability of resource personnel and results in lack of
      infrastructural facilities, which are needed for the identification of accurate
      health indicators in the continent. The challenge is, therefore, great. Local
      officials, psychiatrists, and other mental health professionals must work in
      partnership with each other and with international institutions such as the World
      Psychiatric Association and the World Health Organization to advance the study of
      the cultural framework of illness and health towards upgrading clinical care and
      health promotion of children and adolescents in Nigeria, and more generally, in
      the whole of Africa.

PMID- 11593860
TI  - Psychotherapy in cultural contexts.
AB  - This article examines gender politics, culture, and race, as well as therapy and
      social transition, as they relate to psychotherapy in cultural contexts. Examples
      of gender politics in Kenya and Somalia are discussed. Rites of passage as they
      relate to psychiatric illness also are discussed. "Therapeutic cure" as defined
      in various cultures also is reviewed.

PMID- 11593862
TI  - Culture and the organization of psychiatric care.
AB  - Health care systems of the 21st century confront the confluence of two important
      forces that conform their policies regarding culture. On the one hand, population
      demographics announce increasing diversity; on the other, a rising knowledge base
      regarding the impact of culture on mental health awaits to be incorporated into
      actual clinical practices nationwide. As regulators and payors incorporate this
      knowledge into their practices, standards and guidelines, the dream of mental
      health cultural parity will come somewhat closer to fulfillment. In this article,
      we have aimed to review how the integration of developing knowledge and evolving
      standards may contribute to such fulfillment.

PMID- 11593861
TI  - Culture and psychopharmacology.
AB  - In this brief review the authors strive to provide a broad overview of various
      factors that impinge on psychopharmacotherapeutic practices. The literature
      revealed an impressive progress in research focusing on the delineation of the
      biologic mechanisms responsible for cross-ethnic variations in psychotropic
      metabolism and effects. With the field progressing at an accelerating pace, there
      is little doubt that in the coming decade clinicians will be provided with a
      detailed map showing the prevalence and distribution of genetic polymorphisms of
      most, if not all, of the drug-metabolizing enzymes, and clinicians also will have
      an overall picture on what these polymorphisms mean clinically. At the same time,
      clinicians should also start to have a good grasp on the meaning of the
      variations of the genes that encode therapeutic targets of psychotropics (e.g.,
      neurotransmitter transporters and receptors). Such genetic fingerprinting, which
      will soon become a clinical reality, will provide tremendous help in ensuring
      that pharmacotherapies are increasingly more individually tailored, taking into
      consideration each patients genetic makeups that vary substantially across ethnic
      groups. As exciting as these new developments will be, they are dwarfed by the
      challenges ahead on the cultural side of the equation. Issues that are still
      awaiting further clarification include the following: How do we assess patients'
      beliefs and expectations related to psychotropic treatment? How do we minimize
      the communication gaps between patients and clinicians who are often from
      divergent sociocultural backgrounds? To what extent, and in what ways, do
      cultural (environmental) factors interact with biologic factors, and what might
      be the most efficient way to systematically assess such interactions? Data that
      have emerged in the past several decades clearly indicate the importance of
      culture and ethnicity in influencing patients' psychopharmacological response. It
      is expected that continuing progress in the near future will bring a better
      understanding on the way these cultural and biologic processes, separately and in
      interaction with each other, mediate treatment responses. Such knowledge will be
      crucial for the optimal pharmacotherapeutic care of for the majority of patients
      who will increasingly be of diverse ethnic and cultural backgrounds and will
      represent a significant contribution to the field of psychopharmacology as a
      whole.

PMID- 11593863
TI  - Mental health and illness in traditional India and China.
AB  - Biomedical knowledge underlies the science of all national systems of psychiatry
      and is integral to international psychiatry. It is grounded in Western systems of
      thought, values, and world views. In assessing the cultural and national
      presuppositions of contemporary psychiatry, it is desirable to analyze other
      systems of practice. In this article, some of the characteristics of ancient, non
      Western traditions of mental health and approaches to mental illness are
      discussed. In reviewing salient characteristics of the approach to mental health
      and illness of India and China, one is provided with a vivid illustration of the
      interplay between culture and a system of psychiatric practice. The secular and
      essentially impersonal features of modern biomedical psychiatry contrast with the
      spiritual, value-laden, but also naturalistic basis of ancient traditions and
      approaches to mental health and illness.

PMID- 11593864
TI  - Culture, spirituality, and mental health. The forgotten aspects of religion and
      health.
AB  - Modern psychiatry has neglected the spiritual dimension of the human mind and the
      teleologic concept of illness as meaningful sufferings by clinging to the
      traditional causality principle and rationalistic orientations without clarifying
      the concepts of religion, spirituality, culture, and mental health. The Jungian
      viewpoint may bridge the age-old gap in the West between belief and science.

PMID- 11593865
TI  - Culture and urban mental health.
AB  - The previous panoramic view provides sufficient evidence that cultural
      understanding of urban realities and expressions of their impact on mental health
      are necessary for a successful approach to mental health in cities. The issues go
      beyond understanding how urban realties and cultural issues differ in New York
      from Jakarta; every city has a variety of unwritten cultural norms that permeate
      every aspect of its mental health. Unless these norms are understood within the
      dynamic structure of city living, any attempt to intervene on mental health
      programs will be doomed to failure. Understanding the cultural blueprint of a
      city, however, is only the first step, as we need to shed our cultural
      assumptions while we consider contextual socioeconomic and political factors for
      each city. Finally we need to adapt our western view of cultural values and how
      citizens function or do not function within the urban environments. Because each
      city in is its own culturally specific entity, the three steps outlined
      previously can help create an accurate portrait of what is needed to implement
      culturally sensitive changes. A paradigm shift, laid on a bicurcated foundation,
      on the one hand a locally attuned awareness of urban cultural dimensions and on
      the other educational programs based on extensive knowledge of worldwide problems
      such as stigma, gender-specific issues, disability, and the plight of vulnerable
      populations can potentially have far reaching implications on mental health
      policy changes addressing the cultural needs of cities. Urban mental health is
      poised to be one of the central issues for the next few decades, because of the
      size of the world urban population and because of the protean nature of its
      problems. Cultural factors interplay with urban dynamics in a unique, at times
      creative, other times destructive, fashion. Under conditions of socioeconomic
      disadvantage vulnerable individuals who lack adaptive mechanisms may become
      mentally ill or experience an exacerbation of their mental illness. Understanding
      how cultural dynamics articulate with adaptation to urban life may greatly
      enhance our ability to properly assess and treat mental disorders in cities. In
      the assessment and treatment of patients living in urban areas contextual
      cultural factors rather than being merely complementary assume a preeminent if
      not crucial role.

PMID- 11593866
TI  - Cultural psychiatry: international perspectives. Epilogue.
AB  - The psychiatry of the 21st century will have to be different from the psychiatry
      of the 20th century. The latter began its journey in a socially,
      compartmentalized world in which sharp categories and boundaries for the
      definition of mental illness were assumed to be relevant. International
      psychiatry completed its hegemonic hold over the territory of mental health and
      illness with a commanding home-stretch run of success borne in the confidence and
      optimism of its neurobiologic and culture free program and agenda. The world in
      which psychiatry now exists, however is changing rapidly and will continue to
      change and so of necessity will the practice of psychiatry need to change. This
      issue offers a guidelines and a vision of the direction that should be followed.
      Migration and transnational communication and awareness of cultural differences
      are changing the character of communities around the world. These changes
      considered in the context of world wide political economic factors are bringing
      into close physical and symbolic juxtaposition persons from distinct nations and
      ethnic groups. Clashes in world views, attitudes, spiritual orientation, and
      general philosophic and moral outlook are becoming ever-present realities of
      urban centers around the world. In traditional contexts and among persons who do
      not physically migrate, the power of communications media manages to
      psychologically migrate them; that is, to challenge their local, native cultural
      traditions about mental health with the scientific perspectives about mental
      health and illness. Advances in the social and cultural sciences have underscored
      ways in which assumptions of reductionism and universalism need to be chastened
      with an appreciation of human differences and humane considerations as these
      relate to mental health problems. The science of psychiatry of the 21st century
      will have to accomodate to this new creolized world of ethnic pluralism, cultural
      differences, and clashing perspectives between the traditional and the modern.
      The boundaries, categories, and the conceits governing the closed neurobiologic
      international program and agenda will need to be modified and broadened by the
      addition, sensitivity to and appreciation of cultural differences. This issue has
      reviewed the efforts of scholars around the world who are all deeply committed to
      the goals of the old international psychiatry but judge that a new vision and
      idiom is needed. A responsive international cultural psychiatry is based on a
      blending and integration of all facets of knowledge of the behavioral sciences,
      from biology, pharmacology, genetics on through sociology and cultural
      anthropology. In a new idiom it seeks to provide to all communities of the globe
      the best that the science of psychiatry has to offer in the areas of prevention,
      diagnosis, and treatment. The best psychiatry possible translates as providing
      expert scientific diagnosis and therapy in light of an appreciation of the role
      played by cultural factors in shaping human behavior. Contributors have covered
      the broad terrain of clinical psychiatry in a selective way giving emphasis to
      demographic, regional, and national needs in areas of mental health planning and
      therapy. The reviews of empirical issues and the formulation of conceptual areas
      needing further clarification provide a perspective of what a culturally
      sensitive and responsive international psychiatry should consist of.

PMID- 11593867
TI  - [Perioperative complications in cardiac risk patients. The power of anesthesia to
      decide?].

PMID- 11593868
TI  - [The cardiac risk patient in anesthesia].
AB  - Perioperative cardiac morbidity is one of the main challenges to the
      anaesthesiologist. Because of demographic changes and the increased prevalence of
      coronary artery disease (CAD) in elderly patients, the number of those at risk is
      increasing. Special attention has to be paid to patients bearing an increased
      risk where CAD has not been proven preoperatively because they represent the
      majority. The use of the "Revised Cardiac Risk Index", which includes patient
      related as well as surgery-related risk, is recommended as its predictive value
      is validated to be very high. Additional preoperative testing is indicated only
      in those patients at intermediate risk where functional status is poor or
      unclear. In those with clearly high risk, possibility and urgency of an
      intervention related to their cardiac disease must be weighed against urgency and
      invasiveness of planned non-cardiac surgery. Regarding prophylactic perioperative
      therapy, only beta-blockers can be recommended on a sufficient basis of clinical
      data. This treatment is of special value in patients with poor functional status
      and those undergoing vascular surgery. Postoperative continuation of beta
      blockade for five to seven days is essential to its success. The usefulness of
      alpha-2-blockers is not equally well-proven so far. Prevention of perioperative
      hypothermia can reduce cardiac risk. In addition, there is increasing evidence
      that thoracic epidural anaesthesia decreases cardiovascular morbidity and
      mortality.

PMID- 11593869
TI  - [Quality management in postoperative pain therapy].
AB  - BACKGROUND: Deficits in quality of postoperative pain management are not caused
      by the complexity of the medical problem or shortage of suitable drugs but by
      difficulties in organization and hospital structures. Moreover, there is no
      consensus on how to measure the quality of pain management. Quality management
      programs consist of strategies to overcome such difficulties and to increase
      quality continuously. This study reports the implementation of a quality
      management program to improve postoperative pain management at a university
      hospital. METHODS: An interdisciplinary task force consisting of nursing staff,
      anesthesiologists, surgeons, and members of the hospital pharmacy was set up.
      This task force interviewed patients and performed an analysis of current
      deficits (phase 1). Then, primary and secondary outcome parameters were defined
      to measure quality of pain management, and strategies were defined to implement
      improvements (phase 2). These referred to aspects of organization,
      standardization, and responsibility. One of the main intentions was the
      involvement of nursing staff. After implementation (phase 3), a second analysis
      was performed (phase 4). This was followed by a continuous assessment of
      parameters indicating quality of procedures and results which were fed back to
      all participants (phase 5). RESULTS: After implementation of the program (phase
      4), significantly more patients reported no or mild (NRS < 4) postoperative pain
      (40.2% vs 30.1%) compared to phase 1. Also, patients' satisfaction with pain
      therapy improved significantly. The proportion of patients without pain treatment
      decreased by one-third. Opioids were given more frequently and more often
      intravenously. In contrast, the proportion of i.m. injections decreased from 20%
      to 5%. Continuous assessment of up to now more than 4,900 patients helped to
      identify possible reasons for problems and to maintain overall quality of pain
      management. DISCUSSION: Tools of quality management consisting of deficit
      analysis, definition of outcome parameters, implementation of improving
      strategies, post-intervention analysis and continuous feed-back may be
      successfully used to improve postoperative pain therapy. Changes in organization
      of medical management seem to be more important than medical or technical
      aspects. Similar strategies might be used to increase quality of other medical
      procedures.

PMID- 11593870
TI  - [Atkinson's retrobulbar anesthesia. A quality control study].
AB  - PURPOSE OF THE STUDY: Recognized local and systemic complications of retrobulbar
      anaesthesia (RA) are well known. The purpose of this study was to determine which
      clinical signs predict the success of the RA technique. METHODS: We prospectively
      investigated 500 consecutive patients scheduled for elective eye surgery for
      cataracts and for vitreoretinal procedures. Anaesthesia was administered using
      the Atkinson RA technique while for preoperative quality control, the following
      parameters were recorded: chemosis, eye motility, preservation of vision, active
      eyelid movement, and burning caused by disinfection. For analysis, a
      multidimensional model designed to be useful for forecasting results of the
      anaesthetic outcome was used. The RA was labeled as a "success" when no
      supplementary anaesthetics were required. "Partial success" was defined as an
      incomplete RA with supplementary subconjunctival anaesthetic requirement or an
      anaesthetic given in the form of eyedrops. In the case of "RA failure", the RA
      had to be repeated. RESULTS: The success rate for RA was higher for cataract
      operations than for glaucoma operations. The success rate was not associated with
      the choice of the local anaesthetic, the application of ocular, compression, or
      the anaesthetists and surgeons who performed the RA. Burning caused by
      disinfectant, lid opening and temporal eye motility were found not to be
      associated with a successful outcome. The presence of chemosis had no influence
      on the success of anaesthesia. CONCLUSIONS: The results of this study
      demonstrated that prognostic factors such as defined existing clinical signs, are
      early predictors of the success of the Atkinson RA.

PMID- 11593871
TI  - [Injection pain from propofol-MCT-LCT in children. A comparison with propofol
      LCT].
AB  - OBJECTIVES: This prospective, randomised, double-blind study was designed to
      compare the incidence and intensity of pain on injection of propofol formulated
      in a mixture of medium- and long-chain triglycerides, Propofol-MCT/LCT 1%
      (Propofol-Lipuro, B. Braun, Germany) with propofol in a commonly used emulsion of
      long-chain triglycerides, Propofol-LCT 1% (Disoprivan, Zeneca) in children
      undergoing elective surgical procedures. METHODS: After approval of the local
      ethics committee 40 children, aged 7-14 years, were enrolled in the study.
      Premedication was with 5-10 mg diazepam orally one hour before induction of
      anesthesia. In the beginning 20% of the calculated dose of Propofol for induction
      was injected into a separate venous cannula in a dorsal vein of the hand;
      patients were observed for expressing pain spontaneously during injection
      patients or were asked to describe the sensations after 10 s. Withdrawal of the
      arm during injection was also noted. RESULTS: Significantly more children
      reported pain on injection of propofol-LCT compared to Propofol-MCT/LCT (25% vs,
      10%) and significantly more children retracted their arm during injection of
      propofol-LCT (40% vs. 10%). IMPLICATIONS: Propofol-MCT/LCT 1% (Propofol-Lipuro)
      for induction of anesthesia produced significantly less pain on injection and
      significantly less drawing back of the arm when compared to Propofol-LCT
      (Disoprivan). Thus, with respect to pain on injection Propofol-MCT/LCT appears to
      be superior to Propofol-LCT in children aged 7-14 years.

PMID- 11593872
TI  - [A lost Seldinger technique guide wire as the cause of deep venous thrombosis].
AB  - Five months after the initial abdominal surgery, a female patient presented with
      a deep venous thrombosis of the right leg. A guide wire, lost during perisurgical
      insertion of a central venous catheter using Seldinger's technique, was
      identified and surgically removed. The guide wire had previously remained
      undetected despite regular radiological controls. The article presents details of
      the case together with a review of the literature regarding potential
      complications of Seldinger's technique. Common reasons and possible options for
      preventive and therapeutic strategies will be discussed.

PMID- 11593873
TI  - [The effect of volume status of the right-left shunt in a patient with a patent
      foramen ovale].
AB  - This is a description of the anaesthetic management of a patient with a flow
      patent foramen ovale undergoing intramedullary nailing of the femur. In order to
      detect the flow patent foramen ovale, we used transoesophageal echocardiography.
      During the ventilation maneuver with positive airway pressure of 20 cmH2O, a
      right-to-left interatrial shunt was observed. After the administration of 500 ml
      hydroxy-starch solution (6%) intravenously, detection of the right-to-left shunt
      flow was no longer possible. This case report shows that the volume status in a
      patient with a patent foramen ovale could influence the right to left interatrial
      shunt during general anaesthesia.

PMID- 11593874
TI  - [Evidence-based medicine?].

PMID- 11593875
TI  - [Evidence-based medicine and the systematic review in perioperative medicine].
AB  - The aim of Evidence-based medicine (EBM) is the unbiased and systematic
      identification and synthesis of valid scientific data. These best-evidence data
      may then be used for clinical decision-making. The systematic review is the most
      important tool of EBM and gives a specific answer to a specific question. More
      than 200 systematic reviews have been published in perioperative medicine. They
      treat complications and risks related to anaesthesia, postoperative and labour
      analgesia, nausea and vomiting, regional anaesthesia, blood transfusion and
      fluids replacement, and resuscitation. The majority of these systematic reviews
      are of good quality. In the specific settings of perioperative medicine the
      number of systematic reviews has become so important that recommendations for
      evidenced-based strategies of prevention and therapy can be formulated.

PMID- 11593876
TI  - [German Anesthesia Congress 2001. Nurenburg, June 13-16, 2001].

PMID- 11593877
TI  - The rotameter and the waterwheel.
AB  - The publication imparts information about the personal life and professional
      sphere of activity of J.A. Segner, Karl Kuppers, Maximilian Neu, Hans Bunte, and
      Felix Meyer, as far as they were involved with the invention of devices for
      measuring gas flow, especially their involvement in testing the introduction of
      Rotameters into the medical field. The knowledge that the threat of deportation
      in October 1940, due to his Jewish background and in view of the politics of the
      National Socialists at the time, led to Maximilian Neu's committing suicide, is
      of added historical interest. Together with biographical details, the role played
      by the Institute of Research in Karlsruhe and the establishment of the Rotameter
      site in Aachen is presented. The historical outline finishes with a short report
      of the author's first experience with Rotameters at the Nuffeld Department of
      Anaesthetics, Oxford University during the Second World War and with his
      subsequent efforts to introduce Rotameters into anesthesia equipment design in
      the United States.

PMID- 11593878
TI  - [Fulminant pulmonary embolism following cesarean section. Remarks on the paper of
      U. Grundmann et al., Anaesthesist (2000) 49:1034-1037].

PMID- 11593879
TI  - [Anesthesia for cesarean section and existing inoperable intracerebral angioma.
      Remarks on the paper of M. Raber, Anaesthesist (2000) 49:907-908].

PMID- 11593881
TI  - [Preoperative fasting].

PMID- 11593880
TI  - [Extra myocardial work with of reduction of O2 consumption: end of an illusion.
      Reply to Habler O. et al. (2000). Acute normovolemic hemodilution (ANH). Effect
      of ANH on the diastolic function of the left ventricle. Anaesthesist 49: 939
      948].

PMID- 11593882
TI  - [Removal of dentures for anesthesia].

PMID- 11593883
TI  - [Anesthesiologic management in laser surgical procedures in otorhinolaryngology].

PMID- 11593884
TI  - The end of the beginning: complexity and craftsmanship and the era of sustained
      work on patient safety.

PMID- 11593885
TI  - Patient safety and computerized medication ordering at Brigham and Women's
      Hospital.
AB  - BACKGROUND: Medications are important therapeutic tools in health care, yet
      creating safe medication processes is challenging for many reasons. Computerized
      physician order entry (CPOE), one important way that technology can be used to
      improve the medication process, has been in place at Brigham and Women's Hospital
      (BWH; Boston) since 1993. CPOE AT BWH: The CPOE application, designed and
      developed internally by the BWH information systems team, allows physicians and
      other clinicians to enter all patient orders into the computer. Physicians enter
      85% of orders, with the remainder entered electronically by other clinicians.
      CPOE AND SAFE MEDICATION USE: The CPOE application at BWH includes several
      features designed to improve medication safety--structural features (for example,
      required fields, use of pick lists), enhanced workflow features (order sets,
      standard scales for insulin and potassium), alerts and reminders (drug-drug and
      drug-allergy interaction checking), and adjunct features (the pharmacy system,
      access to online reference information). RESULTS AT BWH: Studies of the impact of
      CPOE on physician decision making and patient safety at BWH include assessment of
      CPOE's impact on the serious medication error and the preventable adverse drug
      event rate, the impact of computer guidelines on the use of vancomycin, the
      impact of guidelines on the use of heparin in patients at bed rest, and the
      impact of dosing suggestions on excessive dosing. CONCLUSION: CPOE and several
      forms of clinical decision support targeted at increasing patient safety have
      substantially decreased the frequency of serious medication errors and have had
      an even bigger impact on the overall medication error rate.

PMID- 11593886
TI  - Developing and deploying a patient safety program in a large health care delivery
      system: you can't fix what you don't know about.
AB  - BACKGROUND: The Veterans Administration (VA) identified patient safety as a high
      priority issue in 1997 and implemented the Patient Safety Improvement (PSI)
      initiative throughout its entire health care system. In spring 1998 the External
      Panel on Patient Safety System Design recommended alternative methods to enhance
      reporting and thereby improve patient safety. REDESIGNING THE PSI INITIATIVE: The
      VA began redesigning the PSI initiative in late 1998. The dedicated National
      Center for Patient Safety (NCPS) was established. Using the panel's
      recommendations as a jumping-off point, NCPS began to identify known and
      suspected obstacles to implementation (such as possible punitive consequences and
      additional workload). NCPS adopted a prioritization scoring method, the Safety
      Assessment Code (SAC) Matrix, for close calls and adverse events, which requires
      assessing the event's actual or potential severity and the probability of
      occurrence. The SAC Matrix specifies actions that must be taken for given scores.
      Use of the SAC score permits a consistent handling of reports throughout the VA
      system and a rational selection of cases to be considered. A system for
      performing a root cause analysis (RCA) was developed to guide caregivers at the
      frontline. This system includes a computer-aided tool, a flipbook containing a
      series of six questions, and reporting of the findings back to the reporter. The
      final step requires that the facility's chief executive officer "concur" or
      "nonconcur" on each recommended corrective action. The RCA team outlines how the
      effectiveness of the corrective action will be evaluated to verify that the
      action has had the intended effect, and it ascertains that there were no
      unintended negative consequences. IMPLEMENTATION: Based on successful
      implementation in two pilots, full-scale national rollout to the 173 facilities
      began in April 2000 and was concluded by the end of August 2000. NCPS supplied 3
      days of training for individuals at each facility. The training included didactic
      components, an introduction to human factors engineering concepts, and small- and
      large-group simulation exercises. Facility leaders were reminded of the necessity
      to reinforce the point that assignment to an RCA team was considered an important
      duty. DISCUSSION: It is essential to design and implement a system that takes
      into account the concerns of the frontline personnel and is aimed at being a tool
      for learning and not accountability. The system must have as its primary focus
      the dissemination of positive actions that reduce or eliminate vulnerabilities
      that have been identified, not a counting exercise of the number of reports.

PMID- 11593887
TI  - The organizational costs of preventable medical errors.
AB  - BACKGROUND: Preventable medical errors are associated with additional costs that
      tend to be borne by patients, but little is known about organizational costs
      associated with such errors. Two composite case studies (a fall and a delay in
      diagnosis) were used to identify the organizational costs of preventable medical
      errors. ANALYSIS: Legal, marketing, and organizational costs--direct, indirect,
      and long term--were associated with each of the preventable medical errors. A
      model was generated to examine the theoretical relationship between the costs and
      four determinants of corporate performance--price, wages, cost of capital, and
      efficiency. DISCUSSION: Organizations may also have a financial incentive to
      improve patient safety, for beyond patient and societal costs, preventable
      medical errors appear to account for significant legal, marketing, and
      operational costs for the organizations that deliver health care. Some of these
      costs are not so much the cost of the error but the costs of organizational
      responses to the error. Three broad areas of inquiry could be used to test the
      model and improve our understanding of the organizational costs of errors: market
      response to patient safety interventions, before/after studies of interventions,
      and case-control studies. SUMMARY AND CONCLUSION: Health care leaders have a
      moral imperative to implement systems that reduce medical errors and improve
      patient safety. An understanding of the costs associated with medical errors may
      help leaders understand the importance of patient safety from a financial
      perspective, develop measures to evaluate the impact of patient safety
      initiatives, and efficiently allocate resources to address this important health
      concern.

PMID- 11593888
TI  - A continuous improvement process for health providers of victims of domestic
      violence.
AB  - BACKGROUND: Health care providers can play an important role in the prevention of
      domestic violence through established processes of identification, safety
      assessment, validation, documentation, and referral. In 1998 the Safe Family
      Project, funded by University Health System (UHS), affiliated with University of
      Texas Health Science Center at San Antonio, provided for a clinical review of
      existing services for victims of domestic violence. A subsequent review of the
      health system's policy and clinical practice supported the need for resources and
      training and for an improved care process for victims of domestic violence. THE
      CONTINUOUS IMPROVEMENT PROCESS (CIP) MODEL: UHS adapted the Shewhart cycle of
      activities popularly referred to as PDSA (plan change, do change, study results,
      act on results), a systematic, process-focused approach to achieving continuous
      and measurable improvement, as its CIP model, and it formed a process improvement
      team. This process led to translation of research findings into best practice
      guidelines for treatment of domestic violence and staff education. RESULTS:
      Significant improvements were made in the overall qualitative chart reviews,
      although the diagnostic coding (using ICD-9 codes and e-codes) did improve. The
      CIP can be replicated in other settings to improve the care of victims of
      domestic violence. DISCUSSION: The CIP effort is being extended to outpatient
      facilities, and managers have requested that the training manual be replicated
      and placed throughout UHS as a resource manual. Other activities are intended to
      improve prevention of domestic violence and intervention when it occurs.

PMID- 11593889
TI  - The Patient Care Notebook: quality improvement on a rehabilitation unit.
AB  - BACKGROUND: Shortened lengths of stay in acute and rehabilitation hospitals,
      continuing financial pressures on all postacute care services, and increasing out
      of-pocket health care costs for patients and families challenge rehabilitation
      hospitals' patient education and discharge planning processes. Spaulding
      Rehabilitation Hospital (Boston) introduced a patient care notebook in a 15-bed
      satellite unit and pilot tested its contribution to the patient education and
      discharge planning process. DEVELOPING THE NOTEBOOK: The three-ring binder
      notebook included sections on medical appointments and phone numbers,
      understanding illness and medical care, coping with illness, physical activities,
      recommendations for the home, and community resources, with both standard and
      patient-specific information. RESULTS: Most of the patients and caregivers who
      received the notebooks found them to be helpful, and most staff indicated that
      the notebook improved the teaching process. Telephone calls to the unit after
      home discharges decreased form 28 calls for 11 discharges to 6 calls for 21
      discharges after the notebook began to be used regularly. DISCUSSION: Staff felt
      that the process of using the notebook helped focus attention on teaching during
      the entire course of a patient's hospitalization rather than just a day or two
      before discharge. The patient care notebook process is being introduced to the
      entire hospital and to all patients, regardless of discharge location and the
      patient's literacy or proficiency with English. CONCLUSION: In using the
      notebook, the QI team, and the entire unit staff, learned about the complexities
      of QI, patient education, and discharge planning. The notebook process was
      implemented throughout the hospital a little more than a year after the
      completion of the pilot project.

PMID- 11593890
TI  - Births to teenagers in the United States, 1940-2000.
AB  - OBJECTIVES: This report presents trends in national birth rates for teenagers,
      with particular focus on the decade of the 1990s. The percent change in rates for
      1991-2000 is presented for the United States, and the change for 1991-99 is
      presented for States. METHODS: Tabular and graphical descriptions of the trends
      in teenage birth rates for the Nation and each State, by age group, race, and
      Hispanic origin, are discussed. RESULTS: Birth rates for teenagers 15-19 years
      generally declined in the United States since the late 1950s, except for a brief,
      but steep, upward climb in the late 1980s until 1991. The 2000 rate (49 births
      per 1,000) is about half the peak rate recorded in 1957 (96 per 1,000). Still the
      U.S. rate is considerably higher than rates for other developed countries. During
      the 1990s rate declines were especially large for black teenagers. State-specific
      rates fell significantly in all States for ages 15-19 and 15-17 years, and in all
      but three States for ages 18-19 years. Overall the range of decline in State
      rates for ages 15-19 years was 11 to 36 percent. For teenagers 15-17 years, the
      range of decline by State was 13 to 43 percent. Reductions by State were largest
      for black teenagers 15-19 years, with rates falling 40 percent or more in seven
      States. The factors accounting for these declines include decreased sexual
      activity reflecting changing attitudes towards premarital sex, increases in
      condom use, and adoption of newly available hormonal contraception, implants, and
      injectables.

PMID- 11593891
TI  - [Treatment results in 25 patients with Graves' ophthalmopathy between 1998 and
      2001].
AB  - In our outpatient clinic 25 patients with Graves' ophthalmopathy were treated, 21
      women, mean age 58.8 years (range 19-74 years) and 4 men, mean age 47.5 years
      (range 38-56 years). In the female group two showed euthyroid Graves'
      ophthalmopathy and one Hashimoto's disease; in the male group one showed
      euthyroid ophthalmopathy. Treatment was done depending on the findings of the
      NOSPECS-classification in identical way for each group. Final results were
      obtained three and six months after therapy, at that time all patients were
      euthyroid. In five patients (two men and three women) sicca-treatment was
      sufficient because the ophthalmopathy improved by therapy of the thyroid disease
      only. Three women were treated by oral steroids over three months and had a
      complete remission. Nine women were treated by oral steroids and external
      radiation, six of them showed major improvement but in one case orbital
      decompression had to be done. Somatostatin therapy was done over six months in
      six women who showed no change after oral steroids plus radiation. Out of them
      five showed major improvement but in spite of a positive octreoscan in one case
      orbital surgery had to be performed. Two men were treated by oral steroids and
      external radiation without change of disease, somatostatin therapy was not done
      because of a negative octreoscan. With the exception of one nonsmoking woman in
      whom orbital surgery had to be done, the treatment results were worse in smokers.

PMID- 11593892
TI  - [Ablative therapy for immune hyperthyroidism in patients with ophthalmopathy].
AB  - The influence of ablative treatment of Graves' disease on the course of endocrine
      ophthalmopathy is discussed controversially. Data are inhomogeneous, because some
      studies were performed retrospectively, some prospectively, because of different
      follow up periods and different patient groups. In principal near total resection
      seems to influence endocrine ophthalmopathy in a positive way, due to the removal
      of thyroid antigen. Most studies also demonstrate that treatment using
      radioiodine has a negative influence on ophthalmopathy, because the course of
      disease is worsening in up to one third of patients. There is also consensus that
      treatment of Graves' disease with radioiodine should be performed only by
      concomitant administration of glucocorticoids. The early administration of L
      thyroxine after radio-iodine therapy of Graves' disease seems to have a positive
      influence on the course of disease, whereas additional treatment with methimazole
      has no positive influence on endocrine ophthalmopathy.

PMID- 11593893
TI  - [Endocrine orbitopathy--eye muscule surgery].
AB  - Extraocular muscles show a typical involvement in Graves' disease, thus inducing
      a characteristic pattern of motility disorders and diplopia. Therapy of choice of
      fibrotic changed muscles is the operation, usually performed by recessions under
      local or even topical anesthesia.

PMID- 11593894
TI  - [Indication and technique of orbital enlargement in the treatment of endocrine
      ophthalmopathy].
AB  - Typical symptoms in endocrine ophthalmopathy are a result of an interstitial
      swelling of the ocular muscles and of the volume increase of the postbulbar fat
      and connective tissue. Clinically, we find a spectrum that reaches from
      infiltration of the eyelid and conjunctival tissue, exophthalmos, swelling of the
      muscles with diplopia, damage to the cornea till to involvement of the optic
      nerve with loss of vision. Regarding functional impairment of the optic nerve,
      orbital decompression represents an operative ultimate ratio. The surgical
      principle is based on the decompression within one or usually several orbital
      walls occasionally in combination with a sagittal enlargement of the eye socket
      by osteotomy and advancement of the orbital rims. As rule of thumb is considered:
      The reduction of the exophthalmos is proportional to the number of decompressed
      walls and amounts to 2-3 mm per decompressed orbital wall. A reduction of
      exophthalmos going beyond that can be obtained by advancement of the orbital
      rims.

PMID- 11593895
TI  - [Orbital decompression in endocrine orbitopathy: advantages and disadvantages of
      different methods].
AB  - Based on the disease activity score, current indications for orbital
      decompression are described. After that, all contemporary decompression
      techniques are mentioned and their advantages and disadvantages are described.
      Transpalpebral fat resection is also included. Results (reduction of proptosis,
      complications) are presented for the coronal and transconjunctival (swinging
      eyelid and transcaruncular orbitotomy) approach used by the author and discussed
      in comparison with other methods.

PMID- 11593896
TI  - [Endocrine orbitopathy--diagnosis].
AB  - Various modifications of classic Werner classification for endocrine orbitopathy
      are used. The application of this NOSPECS-scheme on the ocular and periocular
      changes in Graves' disease is discussed.

PMID- 11593897
TI  - [Interactions of fibroblasts, adipocytes and immunocompeent cells in the
      pathogenesis of endocrine ophthalmopathy].
AB  - Graves' ophthalmopathy is thought to result from a complex interplay of genetic
      and environmental factors. Various genes including those coding for HLA may
      determine a patient's susceptibility to the disease and its severity, but in
      addition numerous and often unknown environmental factors may determine its
      course. The orbital immune process is thought to be initiated, on the background
      of a permissive immunogenetic milieu, by circulating T cells directed against
      certain antigens on thyroid follicular cells that also recognize antigenic
      epitopes which are shared by tissues contained in the orbital space. Analysis of
      variable region genes of T cell antigen receptors in orbital T cells of patients
      with active Graves' ophthalmopathy has revealed limited variability of TcR V gene
      usage, suggesting that antigen-driven selection and/or expansion of specific T
      cells may occur during the early stages of Graves' ophthalmopathy. T cell
      recruitment into the orbital tissues is facilitated by certain chemokines and
      cytokines, which attract T cells by stimulating the expression of several
      adhesion molecules (e.g. ICAM-1, VCAM-1, CD44) in vascular endothelium and
      connective tissue cells. Adhesion molecules are known to be important for a
      variety of interactions between immunocompetent cells, preadipocyte fibroblasts
      and adipocytes. In addition, these molecules play a central role in lymphocyte
      activation and localization, facilitating antigen recognition, T cell
      costimulation, and various effector-target cell functions at the inflammatory
      sites, which result in amplification of the cellular immune process in active
      Graves' ophthalmopathy. T cells and macrophages populate the orbital space and
      release a number of cytokines (most likely a Th-1-type spectrum) into the
      surrounding tissues. Cytokines, oxygen free radicals and fibrogenic growth
      factors, released both from infiltrating inflammatory and residential cells, act
      upon orbital preadipocytes in a paracrine and autocrine manner to stimulate
      adipogenesis, fibroblast proliferation, glycosaminoglycan synthesis, and the
      expression of immunomodulatory molecules. Smoking, a well-known aggravating
      factor in Graves' ophthalmopathy, may aggravate tissue hypoxia and exert
      important immunomodulatory and pro-oxidant effects. Differentiation of orbital
      preadipocyte fibroblasts into mature adipocytes expressing increased levels of
      TSHR may also be driven by stimulation with circulating or locally produced
      cytokines or effectors. TSHR-directed autoantibodies or T cells may thus play a
      direct role promoting adipogenesis, glycosaminoglycan synthesis and expression of
      immunomodulatory proteins within the orbits. Once the net effect of these changes
      has come to increase the volume of the fatty connective tissues within the orbit,
      then proptosis, extraocular muscle dysfunction, and periorbital congestion will
      ensue.

PMID- 11593899
TI  - [Radiotherapy of endocrine orbitopathy--state of the art].
AB  - Since several decades, radiotherapy is included in the multimodal treatment
      concept of Graves' disease. By using orbital irradiation alone or in combination
      with oral corticosteroids up to two thirds of the patients respond to the
      treatment and achieve improvement of soft tissue signs and extraocular muscle
      impairment.

PMID- 11593898
TI  - [Conservative therapy in endocrine orbitopathy: "State of the art"].
AB  - This review describes the state of the art of the conservative therapeutical
      approach of thyroid associated eye disease. Radiotherapy, surgery and ablative
      therapy of thyroid ophthalmopathy are discussed elsewhere in this issue of Acta
      Med Austriaca. All forms of therapy have to be adjusted to the severeness of the
      eye disease. The assessment of the severeness of this ailment can be difficult.
      Therefore, the impact of scoring systems like the "Clinical Activity Score" is
      pointed out. Treatment of thyroid dysfunction is the widely accepted first
      therapeutic measure. Additional supportive local therapy is usually sufficient in
      patients with only mild activity of endocrine ophthalmopathy. Glucocorticoids
      applied via different routes in various dose regimens are the therapy of first
      choice in (moderately) severe forms of the disease. Reported response rates for
      the oral form of therapy are about 63%, for the intravenously applied very high
      doses (given only in very severe forms of the disease) nearly 77%. Cyclosporin
      has been shown to be more efficient in combination with oral glucocorticoids in
      patients with moderately severe eye disease than glucocorticoids alone. Patients
      need a close follow up since both drugs have considerable side effects. An
      alternative treatment with high-dose intravenous immunoglobulins seems to have
      less side effects, but has the disadvantage of bearing the danger of serious
      infections as all plasma derived products and of being extremely expensive.
      Finally, preliminary data of new treatment modalities with the immunomodulators
      pentoxifylline and methotrexat are presented. These drugs have been tested so far
      with good success in patients with severe endocrine ophthalmopathy and
      unresponsive to other forms of treatment.

PMID- 11593900
TI  - [Therapy with somatostatin analogs in patient with orbitopathy and positive
      Octreoscan].
AB  - We prospectively evaluated 28 persons with active endocrine ophthalmopathy and
      positive sonographic criteria (A-mode) on extraocular eye muscles. To evaluate
      somatostatin-receptor status SPECT of the orbits was performed with a double
      headed rotating gamma camera after application of 110 MBq 111-In-Pentreotide. 9
      patients (12/56 eyes respectively) showed a marked uptake ratio (> 2 in circular
      ROIs by semiquantitative calculation) and were selected for lanreotide (30 mg
      i.m. every 14 d) treatment. 5 individuals had control scan after clinical
      progression which became positive in two of them. All but one tolerated modest
      side-effects of lanreotide treatment (diarrhea). Therapy was discontinued after 3
      10 months when thyroid eye disease had lead to fibrotic stage. This subgroup,
      with the exception of two women, who received corticosteroids additionally,
      presented stable disease. One of those had to be sent to surgery because of
      endangered optical nerve. Clinical ophthalmological control showed promising
      results in patients receiving somatostatin analogues at early stage when positive
      on octreo-scan.

PMID- 11593901
TI  - [Oxygen deficiency and erythropoietin].
AB  - Reduced oxygenation activates specific expression of erythropoietin (EPO) and
      other hypoxia-regulated genes. The cellular response to hypoxia is mediated by
      the hypoxia-inducible factor-1 (HIF-1). Unregulated overexpression of EPO results
      in a hematocrit value of about 80%; transgenic mice were shown to adapt to this
      polyglobulia.

PMID- 11593902
TI  - [Epidemiological study of risk factors for Mycoplasma bovis infections in
      fattening calves].
AB  - To establish the role of Mycoplasma bovis as an agent of respiratory disease in
      fattening calves, an epidemiologic study was undertaken. A recently validated
      commercially available ELISA was used to diagnose M. bovis infection by
      seroconversion in paired sera obtained for each animal at entry in the fattening
      herd and at follow-up seven weeks later. Management data as well as relevant
      clinical and epidemiological variables were prospectively recorded. The overall
      seroconversion rate observed among the 415 calves in 23 fattening herds on 13
      farms was 54.7%. Significant risk factors for seroconversion were the mixing of
      fattening herds of different age groups (risk ratio RR 1.70, 95% confidence
      interval (CI) 1.48 to 1.96), and the presence of at least one seropositive animal
      in the fattening herd (RR: 2.02; CI: 1.69 to 2.40). The proportion of clinical
      episodes of respiratory disease attributable to M. bovis infection was 50.3%. The
      average weight gain during the observation period was reduced by 7.6% in
      seroconverting calves and these animals had about 2 times more antibiotics
      prescribed by a veterinarian than calves remaining negative for M. bovis
      throughout follow-up (RR 1.83). Maternal antibodies against M. bovis were
      detected in 39% of newborn calves born from seronegative cows and had a half-life
      of 20 days, potentially limiting the usefulness of vaccines against M. bovis in
      this age group.

PMID- 11593903
TI  - [Orthodontic correction of a complex malocclusion of the canine teeth of dento
      alveolar and skeletal origin using a model cast device in the upper jaw of the
      dog].
AB  - Malocclusion of the canines, which in dogs is frequent and often has a congenital
      pattern, remains a challenge to treat. Steeply positioned lower jaw canines are
      corrected by means of a specifically designed orthodontic intervention. The case
      at hand was characterized by a combination of a slight skeletal distal bite and
      compensatory distal tilt of the entire premaxilla (retrusion, caudal tilt) with a
      mesial tilt of the canines in the upper jaw (rostral and anterior tilt). An
      individual solution was found which resulted in a functional adjustment of both
      upper and lower jaws. A model cast device which included both appropriately
      tilted areas and screws to ensure distal adjustment solved the problem.

PMID- 11593904
TI  - [What is your diagnosis? Keratoacanthoma].

PMID- 11593905
TI  - [Interstitial iodine 125 therapy in localized prostatic carcinoma. Results at the
      Utrecht University].
AB  - At the Utrecht University Hospital Netherlands the preliminary results of
      perineal implantation of I-125 seeds in patients with cancer of the prostate were
      evaluated prospectively. In the period from October 1989 to December 1998, a
      total of 249 patients with localized carcinoma of the prostate were treated with
      perineal implantation of I-125 seeds. Follow-up was every 3-6 months. Results
      regarding progression and complicantions were collected prospectively.
      Progression of the disease was observed in 54 patients: 13 died from carcinoma,
      41 are living with proven relapse. 18 died from intercurrent disease. 25
      developed a local recurrence, 22 a distant relapse, 19 patients only showed a
      rise of prostate specific antigen level, without further symptoms. Acute side
      effects from the urethra were observed in 22 patients: prolonged dysuria in 18,
      acute retention in 4 and urethral stenosis in 3.9 patients had surgical treatment
      of micturition disorders. Four patients suffered from reversible intestinal
      problems. Summarizing perineal I-125 implantation causes few complications and
      may constitute an alternative to external irradiation as well as to radical
      prostatectomy in the treatment of localized carcinoma of the prostate.

PMID- 11593906
TI  - [Natural disease course in untreated early prostatic carcinoma--the Orebro
      Study].
AB  - In a population-based study for prostate cancer, performed in one county in
      Sweden, without screening, disease progression and survival were evaluated. 642
      patients with prostate cancer of any stage consecutively were diagnosed between
      1977 and 1984 at a mid-age of 72 years with complete follow-up. Among 300
      patients with a diagnosis of localized disease (T0-T2) 223 with well
      differentiated histology were treated with hormones only, if they had symptoms of
      tumor progression. In this group the 15-year survival rate, corrected for causes
      other than prostate cancer, was 81%. 77 other patients with localized disease
      received primary treatment with radiotherapy (n = 75) or radical prostatectomy (n
      = 2) +/- hormonal treatment. The survival rate corrected for other causes than
      prostate cancer was identical. In a multivariate analysis, tumor grade turned out
      to be a strong predictor of progression and death due to prostate cancer. The low
      disease--specific mortality rate, especially in patients with highly and
      moderately differentiated tumors, means that any therapy intended for patients
      with early prostate cancer must be evaluated in clinical trials with untreated
      controls for comparison. Without reliable prognostic indicators an aggressive
      approach to all patients with early disease would entail substantial
      overtreatment.

PMID- 11593907
TI  - [Surgical therapy of prostatic carcinoma].
AB  - Radical prostatectomy (RPE) is considered to be the "gold standard" for the
      treatment of localized prostate cancer regardless the fact that up to now no
      prospective randomized trial has compared surgery against radiotherapy,
      brachytherapy or a surveillance strategy. Success of RPE mainly depends on
      patient selection. For patients without extraprostatic tumor growth results of
      RPE are excellent with a rate of 80-90% of patients without biochemical
      recurrence during a 10 year follow up. Despite current staging modalities
      including digital rectal examination, preoperative prostate specific antigen and
      Gleason score of the biopsy between 23-53% of patients will experience PSA
      recurrence during a 10 year follow up. Taken together all sources of presurgical
      information, accuracy of predicting pathological stage it 70%. Decision towards
      or against RPE based on this data may be difficult in the individual patient
      because it is unclear from which possible chance or percentage of cure RPE is the
      adequate treatment. Proper selection of patients is the key to success for
      surgical treatment of localized prostate cancer but we need more accurate
      information including molecular biology technology to predict the biological
      behavior of the tumor.

PMID- 11593908
TI  - [Low dose brachytherapy with seeds--an interdisciplinary therapy alternative to
      radical prostatectomy].
AB  - Prostate cancer is together with the carcinoma of the lung the most common cancer
      in the western world. Better screening methods especially the introduction of PSA
      (prostate specific antigen) in the beginning of the 90's has increased the early
      detection rate. In the United States only 30% of prostate tumors were in their
      early stages before the introduction of PSA-screening as compared to 60%
      nowadays. The early detection also increased the rate of younger men amongst
      these patients. Patient demands have increased with respect to incontinence and
      impotence especially amongst those young patients. Radical prostatectomy still is
      the gold standard for therapy of localized prostate cancer. Better operating
      techniques have decreased the side effect rate of this operations but many
      patients still do not undergo this operation because they fear these side
      effects. Originating from the USA the low dose rate brachytherapy (LDR) using
      permanent seeds had a renaissance in recent years. In 1999 alone more than 40,000
      patients were successfully operated using this technique. 10 year data published
      in 1998 showed similar results as compared to a multitude of radical
      prostatectomy studies and superior results to most of the published external beam
      studies with significantly less side effects. In Germany and western Europe more
      and more centers start with LDR-brachytherapy. In contrary to the U.S. where
      brachytherapy is mostly performed as an outpatient procedure, nearly all European
      centers do only inpatient brachytherapy. Only very few centers perform outpatient
      procedures; the first results are very encouraging showing few complications and
      a very high standard of quality of the treatment.

PMID- 11593909
TI  - [Physical brachytherapy planning].
AB  - The treatment of prostate cancer, confined to the gland, with high conformal
      doses to the target volume and sparing of bladder, rectum and urethra at the same
      time can be achieved by interstitial brachytherapy. Close cooperation of
      urologist and radiologist, together with the physical treatment planning have
      improved the clinical results significantly. The ongoing development of new
      radioactive isotopes and of dedicated computerized treatment planning systems
      have resulted in a renaissance of the interstitial treatment. "Preplanning" i.e.
      preoperative treatment planning can be performed precisely and fast. Improved
      ultrasound techniques allow during the perineal template guided seed implantation
      a realtime dose calculation resulting in an improved seed placement. CT- or MRI
      based "postplanning" guarantees for early postoperative dose documentation and
      quality assurance. 2-dimensional as well as 3-dimensional dose distributions
      superposed to anatomical structures and dose volume histograms (DVH) allow for
      dose optimization and quality decision. 192Ir with high activity is used for the
      high dose rate (HDR) afterloading treatment as a boost after external
      radiotherapy. 125I and 103Pd as well are used as permanent implants to boost
      external irradiation. If fast growing low grade tumors should be treated with
      103Pd permanent implant and slow growing tumors with 125I is discussed
      controversialy. About 50 to 100 seeds are implanted. The implanted patients are
      allowed to leave the hospital as there is sufficient shielding by the surrounding
      normal tissue. Postplanning is based on CT- or MRI for dose documentation and
      quality assurance. For 125I treatments the activity-dose-relation was redefined
      since 1995 (TG43 protocol). Similar corrections seem to be necessary for 103Pd
      treatments.

PMID- 11593910
TI  - [Treatment error or erroneous treatment? Theodor Kocher and total excision of the
      thyroid gland 1883-1914].

PMID- 11593911
TI  - [Combined treatment in asthma].

PMID- 11593912
TI  - [Asthma risk factors].
AB  - OBJECTIVE: To study the magnitude of risk factors known for asthma in 6-10 year
      old children. MATERIAL AND METHODS: This is a case- and control-study with 6-10
      year-old children; 58 were asthmatic and 117 were control, with a relation 2:1.
      Asthmatic patients were recruited from consult of immuno-allergies department and
      control patients, from familial medicine consult of Hospital de Especialidades
      71, IMSS. Indirect (mother) and directed surveys were applied, they were of
      multiple option for exploring the most known in literature-risk factors.
      Statistical management was performed by odds ratio with confidence interval of
      95%. RESULTS: The following variables were considered risk factors: ingestion of
      artificial colorants before having 1 year old (OR = 13.2), living in an urban
      area (OR = 7.74), maternal smoking during pregnancy (OR = 2.4), wool contact
      before having 1 year old (OR = 2.11), passive smoking exposure during pregnancy
      (OR = 1.486) and feeding with industrialized milk (OR = 1.2). CONCLUSIONS:
      Environmental risk factors are very important in our population, as well as early
      ablactation; however, ingestion before having 1 year old of allergens as egg,
      chocolate, orange and mango was not considered risk factor.

PMID- 11593913
TI  - [Clinical and spirometric correlation with home allergens and with pollutants].
AB  - INTRODUCTION: Environmental contamination causes an increase in respiratory
      symptoms, especially in patients with asthma. The severity of allergic asthma in
      children is associated with the presence of intradomicilliary aeroallergens and
      intramural contaminants. OBJECTIVE: Correlation to clinical abnormalities,
      spyrometryand skin test with the intradomiciliary pollution. MATERIALS AND
      METHODS: Children who participated ranged in age from 6 to 15 years, attended
      public schools, and were classified as healthy and asthmatic. A questionnaire was
      applied to them, as well as a clinical history, spirometry, skin tests, and an
      environmental study at home. RESULTS: Fifty-seven children were studied, of 10
      years of age (+/- 3). Group 1 (23 healthy children): Positive skin tests, dust
      66.6%, cockroaches 66.6%, mites 33.3%, cat 33.3%, dog 4.3%. Principal clinical
      symptoms were cough 91.3%, wheezing 78.3%, respiratory difficulty 39.1% with a
      morning predominance of 78.3%. Spirometry showed an obstructive pattern in 30.5%.
      Group 2 (34 asthmatic children): Positive skin tests, mites 52.1%, dust 47.8%,
      cockroach 21.7%, cat 21.7%, dog 4.3%, passive exposure to tobacco smoke 79.5%.
      Principal clinical symptoms were cough 91.3%, respiratory 82.3%, wheezing 79.4%,
      predominantly at night 70.5%. Spirometry showed obstructive pattern in 67.7%.
      CONCLUSIONS: Children with asthma present great contact and sensitivity for
      intradomicilliary allergens such as mites in household dust, proteins from cat,
      dog, and cockroach feces, in addition to greater frequency of passive smoking. It
      is important to point out that these factors can be modifiable at low cost, thus
      presenting the conditions for a better quality of life for the patient and
      diminishing costs of medical attention.

PMID- 11593915
TI  - [Prevalence and asthma risk factors in municipalities of the State of Guerrero,
      Mexico].
AB  - OBJECTIVE: To determine the incidence and the principal risk factors cause of
      asthma in scholar children between 4 to 6 years old and in adolescents students
      between 13 to 14 years old in six municipalities in Guerrero State, Mexico.
      MATERIAL AND METHOD: A cross-sectional study was carried out with 6,136 students
      (both groups) in the Acapulco municipality on the second semester of 1999 and
      with 1,128 students in municipalities near to Acapulco in the first semester of
      year 2000. The procedure was to use the questionnaire ISAAC to interview the
      mothers of the children between 4 to 6 years old, and apply directly interviews
      to the 12 to 14 years old group. The study was carried out in public school with
      the more social recognition. RESULTS: Asthma prevalence in the Acapulco
      municipality was 33.55%. Detected in girls 34.8% and 32.0% in boys. In the rural
      municipalities near Acapulco the asthma prevalence was of 31.8%. Detected in
      girls 34.0% and 29.2% in boys. One of the principal risk factory cause of
      incidence in the urban area of Acapulco was the presence of the cement factory.
      In the rural area near Acapulco the principal risk factor was the common presence
      of cotton toys. A very high asthma incidence was identified in the studied
      municipalities. The principal group affected was the students between 13 to 14
      years old without a remarkable difference between gender in the urban areas.

PMID- 11593914
TI  - [Immediate reaction to latex: comparison between skin test and IgE determination
      with ELISA].
AB  - BACKGROUND: Development of latex hypersensitivity type 1 response mediated by IgE
      depends on exposition intensitivity and genetic predisposition. Clinical
      manifestations are urticaria, rhinoconjunctivitis, asthma and anaphylaxis.
      OBJECTIVE: The aim of the study was to determine the frequency of latex immediate
      skin reactivity on allergy patients from 1-15 yr old from Hospital Infantil de
      Mexico. METHODS: A clinical, prospective trial was performed between november
      1998 and april 1999. During the study we documented 629 patients with allergy. Of
      them 30 had positive skin prick test (SPT) to latex according to Aas
      classification and 30 with negative SPT were randomly chosen as control group.
      Both groups were similar with respect to diagnosis, age, and sex characteristics.
      RESULTS: 629 children's with SPT, 30 had positive skin princk test (4.76%), 15
      men and 15 women, with an average age of 8.9 years. For groups 1-5 years of age.
      The group age 6-10 years 6.21% and that of age 11-15 8.9%. Atopia antecedent
      73.3%. For rhinitis and asthma diagnostic 63%, rhinitis 13%, asthma 20%,
      conjunctivitis 20%, atopic dermatitis and anaphylaxis 3.3%, urticaria 6.6%.
      Surgery antecedent 30%. 100% used a sucking, 93% used a latex toy the
      relationship of symptoms with the use of latex was 6.6%. Statistica1 ana1ysis was
      performed using: Nonparametric correlations the Kendall's tau-b: 0.329 and
      Spearman's rho 0.348 correlation is significant. CONCLUSION: It does exist a
      correlation between SPT and test for latex-especific IgE antibodies, the older
      the patient, the higher frequency of latex reaction, history of atopy is the
      mayor risk factor.

PMID- 11593916
TI  - [Effect of naproxen on serum concentrations of IL-I, IL-6, and TNF in patients
      with osteoarthritis].
AB  - AIMS: Non-steroid anti-inflammatory drugs can inhibit bone loss and preserve bone
      mineral density in in vitro models by inhibiting prostaglandins and inflammatory
      cytokines. Naproxen inhibits prostaglandin and cytokine biosynthesis. Our
      objective was to assess the effect of naproxen on the serum levels of IL-I, IL-6
      and TNF in 18 patients with osteoarthritis. MATERIAL AND METHOD: Two groups of
      nine patients each were formed randomly. One of them received naproxen 10 mg/kg
      BW bid for 2 weeks, and the other received placebo and paracetamol as needed.
      Cytokines were measured before and 2 weeks after naproxen administration by ELISA
      test. RESULTS: Serum IL-I and IL-6 levels were reduced in the group receiving
      naproxen, suggesting a reduction of the degenerative changes in the patients with
      osteoarthritis, that may prevent the progression of the disease.

PMID- 11593917
TI  - University of Iowa's top-to-bottom site upgrade.

PMID- 11593918
TI  - New Eastern Maine Healthcare site takes aim at Maine's health challenges.

PMID- 11593919
TI  - Getting the most from your Internet news releases.

PMID- 11593920
TI  - Baptist Health buys health information but maintains its own branding.

PMID- 11593921
TI  - Myocyte death and myocyte regeneration in the failing human heart.

PMID- 11593922
TI  - Ion current alterations in myocardial hypertrophy.

PMID- 11593923
TI  - Different patterns of pulmonary venous flow in myocardial hypertrophy:
      hypertrophic cardiomyopathy versus athlete's heart.

PMID- 11593924
TI  - Coronary vasodilator reserve in left ventricular hypertrophy.

PMID- 11593925
TI  - Anti-vimentin antibodies are an independent predictor of transplant-associated
      coronary artery disease following cardiac transplantation.

PMID- 11593926
TI  - Early risk factors for transplant coronary artery disease and cardiac allograft
      failure.

PMID- 11593927
TI  - Inflammatory markers of ischemic coronary syndromes.

PMID- 11593928
TI  - Genetics and early-onset myocardial infarction.

PMID- 11593929
TI  - Influence of advanced glycation end-products in the development of
      atherosclerosis.

PMID- 11593930
TI  - Oxidative elements in the pathogenesis of atherosclerosis.

PMID- 11593931
TI  - Ischemia-reperfusion and microvascular dysfunction: implications for salvage of
      jeopardized myocardium and reduction of infarct size.

PMID- 11593932
TI  - Interaction between the endothelium and blood cells in acute coronary syndromes.

PMID- 11593933
TI  - Endothelial dysfunction and heart failure.

PMID- 11593934
TI  - Mechanisms of inotropic effects induced by nitric oxide.

PMID- 11593935
TI  - Recent advances in the diagnosis and treatment of diabetic cardiomyopathy.

PMID- 11593936
TI  - Maintaining corneal integrity how the "window" stays clear.
AB  - The anterior surface of the eye is composed of the cornea, conjunctiva, and the
      zone between the two called the limbus. The cornea must maintain optical clarity
      to retain good vision. However, the ocular surface is vulnerable to trauma,
      microbial infection, and exposure to environmental toxins. This places the
      cornea, especially, at risk for disruptions of the epithelial barrier and
      subsequent immunopathological events. Cell-cell and cell-matrix attachment
      junctions incorporating adhesion molecules ensure that the epithelial barrier
      remains intact. Protein components of the basement membrane, including laminins,
      are vital to the adhesion of corneal epithelial cells to the underlying stroma
      and function to enhance the strength of the bond between epithelium and
      connective tissue. Epithelial cells also play an early and crucial role in the
      initiation of ocular surface responses should a potentially antigenic molecule
      enter into deeper corneal tissues. For example, epithelial cells may produce and
      release cytokines such as interleukin-1 (IL-1). The delicate balance between the
      matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases
      (TIMPs) are central to mechanisms regulating dissolution of the extracellular
      matrix that may be a consequence of infection or wound healing. Adhesion
      molecules, cytokines and chemokines, and MMPs and TIMPs thus participate in the
      corneal response to immunologic challenge or wounding. They may also be involved
      in corneal pathologies associated with genetic diseases, diabetes, and vitamin A
      deficiency. In addition these molecules are components of cellular pathways
      underlying the clinical complications often observed with contact lens wear and
      refractive surgeries used to improve visual acuity.

PMID- 11593937
TI  - A social categorization approach to distributive justice: social identity as the
      link between relevance of inputs and need for justice.
AB  - What are relevant inputs or criteria for judging entitlements in a given
      situation? As will be argued, an answer to this central problem of distributive
      justice must consider the perceiver's self-definition and structuring of the
      social context, in terms of social categorizations. The construal of the primary
      category of potential recipients is particularly important as its prototypical
      dimensions are likely criteria for entitlement judgments. Its representation
      depends on the perceiver's salient identity. Two studies yielded support for this
      perspective. In Study 1, students regarded their psychology department's
      distinctive quality as more important for psychologists than an out-group's
      quality. When highly identified, they perceived a psychologist who outperformed
      another on the in-group quality to have a higher entitlement to a job. In Study
      2, German participants regarded the European Union's (EU) denial of EU membership
      to Turkey as more just the more prototypically European they thought Germany was,
      in contrast to Turkey; and, in turn, they did so the more strongly they
      identified as Germans. The findings suggest that relevance of inputs and, thus,
      the justice motive are based on identity concerns.

PMID- 11593938
TI  - The affective and memorial components of distinctiveness-based illusory
      correlations.
AB  - Two studies were conducted to test a model of the distinctiveness-based illusory
      correlation (IC) phenomenon that suggests there are two components operating with
      ICs: cognitive memorial, and affective. In Expt 1 (N = 118), two stimulus arrays
      were developed that were equivalent in regards to valence (good or bad extremity)
      but differed in regards to the affect dimension (high or low emotional
      intensity). Consistent with predictions drawn from the proposed model, the
      magnitude of the IC effect was higher in the high emotional intensity than in the
      low emotional intensity condition, but only significantly so on the measures
      (estimation and general evaluation) that have been hypothesized to be most
      sensitive to the affective component. In Expt 2 (N = 52), the affective qualities
      were matched and the valence properties varied in two stimulus arrays. As
      predicted, the IC effect differed significantly between conditions only on the
      measure (assignment) thought to be most sensitive to the memorial component. The
      results are discussed in terms of the implications of the findings for the
      proposed mechanisms of illusory correlation.

PMID- 11593939
TI  - 'Hooligans' abroad? Inter-group dynamics, social identity and participation in
      collective 'disorder' at the 1998 World Cup Finals.
AB  - During the 1998 Football World Cup Finals in France, English supporters were,
      once again, involved in major incidents of collective 'disorder'. Explanations
      for these incidents concentrated on the conflictual norms held by 'hooligans'. In
      contrast, Scottish supporters attending the tournament displayed norms of non
      violence, explained by the popular press in terms of the absence of 'hooligans'.
      This study challenges this tendency to explain the presence or absence of
      'disorder' in the context of football solely in terms of the presence or absence
      of 'hooligan' fans. Using data obtained from an ethnographic study of both
      Scottish and English supporters attending the tournament (N = 121), we examine
      the processes through which ordinarily 'peaceful' supporters would or would not
      become involved in collective conflict. In line with the Elaborated Social
      Identity Model (ESIM) of crowd behaviour, the analysis highlights the role of the
      intergroup context. Where out-group activity was understood as illegitimate in in
      group terms, in-group members redefined their identity such that violent action
      toward out-group members came to be understood as legitimate. By contrast, where
      there was no out-group hostility, in-group members defined themselves through an
      explicit contrast with the 'hooligan' supporters of rival teams. This analysis
      represents an advance on previous studies of crowd behaviour by demonstrating how
      the ESIM can account for not only the presence, but also the absence, of
      collective 'disorder'.

PMID- 11593940
TI  - Cultural variation in hemifacial asymmetry of emotion expressions.
AB  - Photographs of hemifacial composites (left-left, right-right and normal
      presentation, right-left) of these cultures (Japanese, Oriental Indian and North
      American) displaying six emotions (happy, sad, fear, anger, surprise, disgust)
      and a neutral state were administered successively (one by one) as well as
      simultaneously (three hemifacial photographs of an expression at a time) to
      observers for judgment on a 5-point scale in terms of distinctiveness of
      expression. Observers' judgments were treated with a culture of expressor x sex
      of expressor x facial presentation x emotion category mixed factorial ANOVA.
      Cultures did not vary for their distinctiveness of facial expressions, suggesting
      universality in this respect. Culture-specificity was, however, observed with
      respect to hemifacial asymmetry and valence of emotion expressions: (1) Japanese
      showed a right hemifacial bias for positive and left hemifacial bias for negative
      emotions; Indians and North Americans showed left hemifacial bias for all
      emotions, and (2) negative emotion expressions were least distinctly identifiable
      in Japanese faces followed by Indian and North American faces.

PMID- 11593941
TI  - Identifiability and self-presentation: computer-mediated communication and
      intergroup interaction.
AB  - This research investigated the intergroup properties of hostile 'flaming'
      behaviour in computer-mediated communication and how flaming language is affected
      by Internet identifiability, or identifiability by name and e-mail
      address/geographical location as is common to Internet communication. According
      to the Social Identity Model of Deindividuation Effects (SIDE; e.g. Reicher,
      Spears, & Postmes, 1995) there may be strategic reasons for identifiable groups
      members to act in a more group-normative manner in the presence of an audience,
      to gain acceptance from the in-group, to avoid punishment from the out-group, or
      to assert their identity to the out-group. For these reasons, it was predicted
      that communicators would produce more stereotype-consistent (group-normative)
      descriptions of out-group members' behaviours when their descriptions were
      identifiable to an audience. In one archival and three experimental studies, it
      was found that identifiability to an in-group audience was associated with higher
      levels of stereotype-consistent language when communicators described anonymous
      out-group targets. These results extend SIDE and suggest the importance of an in
      group audience for the expression of stereotypical views.

PMID- 11593942
TI  - Broadcasting the royal role: constructing culturally situated identities in the
      Princess Diana Panorama interview.
AB  - We examine critically the two traditions of work that have informed discursive
      approaches to identity: social constructionism and conversation analysis. Within
      both strands, identity is theorized as a flexible phenomenon that is situated in
      conversations. But although constructionists locate identity within the social,
      such work remains at a theoretical and rather abstract level and often fails to
      interrogate the discursive practices through which identity is constituted.
      Conversely, this attention to the occasioning of identity in everyday talk is
      precisely the focus of the second, conversation analytic strand of work. Whereas
      constructionists attend to the wider cultural positioning of identities,
      conversation analysts resist commenting upon the social significance of what is
      constructed in interaction. Conversation analysis is therefore limited by its
      restricted notion of culture in the study of the situated social self. Despite
      the apparent conflict between these approaches, we suggest that a synthesis of
      the two provides a comprehensive framework for analysing identity. Drawing upon
      the BBC Panorama interview between Martin Bashir and Princess Diana, we explore
      how culturally situated identities are located in this conversational context. We
      conclude that analysts must not only attend to the micro-level organization of
      identities but also engage in a wider understanding of the cultural framework
      within which they are located.

PMID- 11593943
TI  - An existentialist view on mortality salience effects: personal hardiness, death
      thought accessibility, and cultural worldview defence.
AB  - Two studies examined the possible moderating role of hardiness on reactions to
      mortality salience inductions. A sample of 240 Israeli undergraduate students
      completed a hardiness scale, were exposed to a mortality salience or control
      induction, and then either rated the severity and punishment of 10 social
      transgressions (Study 1, N = 120) or performed a word-stem completion task, which
      tapped the accessibility of death-related thoughts (Study 2, N = 120). Results
      indicated that a mortality salience induction led to more severe judgments of
      social transgressions as well as to more severe punishments than a control
      induction only among participants scoring low in the hardiness scale. However, a
      mortality salience induction led to a higher cognitive accessibility of death
      related thoughts than a control condition regardless of participants' hardiness
      scores. The discussion emphasizes the importance of considering inner resources
      when examining reactions to mortality reminders.

PMID- 11593944
TI  - Group variability judgments: investigating the context-dependence of
      stereotypicality and dispersal judgments.
AB  - This study explores the context-dependent nature of perceptions of group
      variability by examining how ingroup and outgroup ratings are affected by asking
      participants (N = 237) to rate these groups either on their own or together. In
      key respects, it replicates the design utilized by Haslam, Oakes, Turner, and
      McGarty (1995). However, several features of the present study's design were
      distinctive and intended to address methodological issues raised in the original.
      First, an alternative to the Katz-Braly procedure was adopted such that the
      measure of 'stereotypicality' referred to the applicability of both stereotypic
      and counter-stereotypic attributes. Second, a measure of 'dispersion' was also
      employed. The data show that ingroup stereotypicality was, as predicted, affected
      by a manipulation of context, while outgroup stereotypicality was not. No effects
      of context on the dispersion measures were obtained for either the ratings of the
      ingroup or the outgroup. The relationship between stereotypicality and dispersal
      measures of variability is discussed.

PMID- 11593945
TI  - Generalisability and classical test theory analyses of Koppitz's scoring system
      for human figure drawings.
AB  - BACKGROUND: Scoring systems to evaluate children's human drawings for
      intellectual maturity have been found to have good intra- and inter-scorer
      reliability. However, there is some evidence (McCarthy, 1944) that such scores
      may not be stable over time. AIM: The aim of the study was to investigate raters
      and occasions as potential sources of error in children's Draw-a-Person scores
      using generalisability and classical test theory. SAMPLE: The sample consisted of
      85 school children (45 girls and 40 boys) aged between 8 years 1 month to 9 years
      and 7 months. METHOD: The Koppitz Draw-A-Person (1968) test was administered as a
      class test on two occasions with exactly a two-week interval between the
      occasions. All the children's drawings were scored by the same four raters.
      RESULTS: Generalisability analyses of the Koppitz scores indicated that the
      variance components for raters and its interaction with both persons and
      occasions were very small, suggesting that very little measurement error was
      associated with the raters. However, the estimated variance component for the
      interaction of persons by occasions was substantial. With four raters and two
      occasions the generalisability coefficient was .47. These results were consistent
      with the classical test theory analysis which indicated generally high inter
      rater reliabilities but a low test-retest reliability, based on a composite of
      the four raters. CONCLUSION: If satisfactory levels of
      reliability/generalisability are to be achieved with the Koppitz scoring system
      children have to be tested on several occasions.

PMID- 11593946
TI  - An examination of situational interest and its sources.
AB  - BACKGROUND: Situational interest is articulated theoretically as a construct
      associated with five dimensional sources: novelty, challenge, attention demand,
      exploration intention, and instant enjoyment. AIMS: This study aimed to examine
      the influence of the dimensional sources on situational interest. It was
      hypothesised that the dimensional sources function differently to contribute to
      situational interest and that the influence of a source might be mediated by
      others. SAMPLE: Two samples of 7th, 8th, and 9th grade students were used in the
      study. There were 281 students (57% male, 43% female) in the first sample and 191
      (47% male, 53% female) in the second. METHOD: Students in Sample A evaluated
      situational interest and the dimensional sources in tasks of analysing jogging
      and gymnastic stunts on video. Those in Sample B evaluated them in tasks of
      learning basketball. Correlation and regression analyses and path analyses were
      used to test the theoretical model. RESULTS: Instant Enjoyment determined
      situational interest. Exploration and Novelty had positive influences on
      situational interest via enhancing Instant Enjoyment. Challenge showed little
      influence. The path analyses for both samples confirmed the inter-dimensional
      mediation effects of the sources. CONCLUSION: The analysed data support the
      hypotheses. The dimensional sources had unequal influences on situational
      interest and the mediation effects among themselves at times strengthened or
      weakened each other's influences. The findings suggest that to increase
      situational interest, educators should offer students ample exploratory
      opportunities during student-task interaction that can lead to instant enjoyment
      for learning.

PMID- 11593947
TI  - Optimism, hostility, and adjustment in the first year of high school.
AB  - BACKGROUND: The period of transition to high school is marked by large variations
      in student adjustment patterns. Many students make successful adjustments but
      others do not and are at risk of developing hostile attitudes towards their
      school environment. AIMS: This study sought to investigate the role of optimism
      and pessimism in predicting the extent of hostility students express towards
      school. SAMPLE: The sample consisted of 102 students who completed questionnaires
      at the beginning of the school year, and also in the last term of their first
      year at high school. METHODS: Students responded to questionnaires assessing
      their levels of (a) dispositional optimism and pessimism, (b) personal
      expectancies for the occurrence of specific negative events, and (c) depression
      and anxiety. Additional data concerning hostility to school, perceived classroom
      involvement, and student adjustment (self-reported and teacher-reported) to
      school measures were collected at the end of the year. RESULTS: In general, the
      girls reported greater levels of positive adjustment than boys. It was found that
      optimism together with expectations of negative events accounted for 21% of the
      variance in school hostility. In addition, optimism was significantly related to
      classroom involvement and to students' self-reported adjustment. Teachers'
      ratings of student adjustment were related only to gender. Only 15 (12 male, 3
      female) of the 102 students were clearly hostile towards the school. CONCLUSIONS:
      We conclude that young people are vulnerable to adjustment problems when levels
      of dispositional optimism are not sufficiently strong to counteract high
      expectations about the possibility of specific negative events occurring.

PMID- 11593948
TI  - Predicting early grade retention: a longitudinal investigation of primary school
      progress in a sample of rural South African children.
AB  - BACKGROUND: One hundred and fifty rural South African children, newly enrolled in
      Grade 2 in 1994, were retraced in 1998 when they were scheduled to have entered
      Grade 7. Only 39% of the cohort had progressed smoothly to Grade 7; more than a
      third (36%) had left their original primary school, and 25% had been retained at
      least once. AIMS: The present study investigated factors that were measurable at
      the start of Grade 2 which proved useful in predicting subsequent retention.
      METHOD: Details of children's academic progress from Grade 1 in 1993 through all
      subsequent years including 1998 were collected. Predictor variables included age
      at school entry, sex of child, nutritional status, academic achievement in Grade
      1, cognitive test status at Grade 2, teacher assessments of children's behaviour,
      and biographical variables such as caregiver education and household size.
      RESULTS: Rural children's experience of primary school was relatively disrupted.
      For those who remained in the same school, a relatively good predictive model for
      retention was built, with Grade 1 academic achievement as well as caregiver
      education, and cognitive test scores being important predictors. CONCLUSIONS:
      Results corroborate those of developed world studies, in showing that early
      academic achievement is a strong predictor of retention. In addition, they
      highlight the importance of early curriculum mastery--rather than broader
      cognitive skills--for smooth progression through school.

PMID- 11593949
TI  - Approaches to study of three Chinese national groups.
AB  - BACKGROUND: Although numerous studies have examined the learning approaches of
      Chinese students, very few comparative studies have been carried out with Chinese
      students from different nations. AIMS: The present research was designed to
      identify differences in study approach between Chinese university students drawn
      from Malaysia, Singapore, and Hong Kong. SAMPLES: The sample consisted of 192
      Chinese students with 89 students from Malaysia (43 males and 46 females), 65
      students from Hong Kong (41 males and 24 females), and 38 students from Singapore
      (12 males and 26 females). METHOD: All students completed Entwistle and Ramsden's
      (1983) Approaches to Studying Inventory by rating on a 4-point Likert scale how
      well each of the 64 items described their own learning behaviour. RESULTS: The
      hypotheses that, in comparison with their respective counterparts, Malaysian
      Chinese students would identify themselves as being more dependent in their
      learning, Singaporean students as being more adept in presenting ideas/concepts
      in a clear and systematic fashion, and Hong Kong students as being more anxious
      in their learning approach, were all supported. However, the hypothesis that Hong
      Kong students would be more strategic in their learning approach than their
      national counterparts was not supported. CONCLUSIONS: Based on the significant
      differences in learning approaches noted among the different Chinese subgroups,
      caution must therefore be taken against forming fixed conceptualisations of
      cultural characteristics and considerable care be given in sample definition and
      selection in cross-cultural research.

PMID- 11593950
TI  - Identifying and assessing the conceptions of teaching of secondary school physics
      teachers in China.
AB  - BACKGROUND: Recent research indicates that how lecturers think about the nature
      of teaching influences both the way they teach and the way their students learn
      and ultimately the learning outcomes they achieve. Such research has primarily
      been conducted at the tertiary level in Western countries and its relevance for
      school teaching and in non-Western contexts has yet to be demonstrated. AIMS:
      Study 1 aimed to develop a model of the conceptions of teaching of Chinese
      secondary school teachers of physics and an instrument to assess these
      conceptions. Study 2 then tested the reliability and within-construct validity of
      responses to the latter and the relationships between teaching experience and
      gender and teaching conceptions were investigated. SAMPLE: The interview sample
      in Study 1 comprised 18 teachers of physics in Guangdong, China. The instrument
      was administrated to 450 physics teachers from the province in Study 2. METHOD:
      An in-depth emic approach involving both interviews and classroom observations
      was utilised to develop the model. Confirmatory factor analysis was used to test
      the fit of responses to the instrument to the proposed model. RESULTS: Five lower
      order conceptions (Knowledge Delivery, Exam Preparation, Ability Development,
      Attitude Promotion, and Conduct Guidance) and two higher order orientations
      (Moulding and Cultivating) were identified. Responses to the instrument were
      found to be of satisfactory internal consistency reliability and to fit the
      expected underlying factor model. Neither teaching experience nor gender was
      found to be related to conceptions of teaching. CONCLUSIONS: The model developed
      differed in some respects from those found in the Western tertiary literature due
      probably to cultural factors which emphasise more an affective, moral view of
      teaching and to a school contextual emphasis on exams. The instrument developed
      had very adequate psychometric properties and seems promising as a tool for
      assessing teaching conceptions in future research within China and across
      cultures.

PMID- 11593951
TI  - Learning-related behaviours versus cognitive ability in the academic performance
      of Vincentian children.
AB  - BACKGROUND: The few studies of children's academic performance in developing
      countries have largely focused on effects of early risks and cognitive ability
      and usually neglected other factors such as attention and anxiety. Previously, we
      reported that scores on the Learning Behaviour Scale (LBS) and the Revised
      Behaviour Problem Checklist (RBPC) were correlated with academic scores and
      achievement test scores for village children in St Vincent, the West Indies.
      AIMS: We examined the stability of LBS and RBPC scores and their ability to
      predict academic and achievement scores in the same population. SAMPLE:
      Vincentian village children, ages 6-12, participated in the study: 65
      participated in the one-year sample and 68 participated in the two-year sample.
      METHOD: Children completed a curriculum-based achievement test and the Raven
      Coloured Progressive Matrices. Teachers completed the LBS and an adjusted RBPC
      and reported children's academic scores in 1998 and 1999. RESULTS: LBS scores
      were stable over one year and RBPC scores were stable over two years. LBS, RBPC,
      and Raven scores predicted achievement and academic scores. For both academic
      scores and achievement test scores, the greatest improvement in prediction came
      when the RBPC's attention and anxiety subscales were added to regression models.
      CONCLUSIONS: Results provide additional support for the finding that Caribbean
      village children's academic performance is greatly influenced by attention and
      anxiety problems, not just their cognitive ability. Despite cultural differences,
      LBS and RBPC scores were as predictive of academic performance in this population
      as in American populations. The best way to improve academic performance for
      these children may be to reduce attention problems.

PMID- 11593952
TI  - Analysis of repertory grids in clinical practice.
AB  - OBJECTIVES: This paper illustrates the use of several different forms of analysis
      of repertory grid data, using a case study of a client who completed repertory
      grids at various stages of therapy. METHOD: Participants in a survivors' group
      completed grids before and after therapy and at 3- and 6-month follow-up. Grids
      from one of the participants, who had been sexually abused as a child, are
      presented using different levels of analysis: visual inspection of the raw grid;
      analysis of dissimilarities between pairs of elements or constructs; hierarchical
      cluster analysis of elements and constructs both separately and combined;
      principal components analysis; biplot representation of elements and constructs
      combined; multidimensional scaling analysis and unfolding analysis. The latter
      two methods also provide ways of presenting a combined analysis of a number of
      grids. Computer packages are reviewed, and SYSTAT commands are presented to
      perform the analyses. RESULTS: The review of methods illustrates how different
      levels of analysis can usefully back up clients' own accounts of progress through
      therapy, from detailed analysis of individual ratings in the raw grid, through
      analyses that pull out structural patterns at the expense of detail, to the broad
      sweep provided by methods that combine data from a number of grids. CONCLUSIONS:
      Analysis of repertory grids completed at various stages of therapy can provide
      useful qualitative information on progress, but can also provide some simple
      quantitative measures (such as Self-Ideal Self discrepancy as a measure of self
      esteem) to track progress. Different forms of analysis can be informative,
      highlighting different aspects of progress, but also allowing checks on adequacy
      and goodness-of-fit of particular analyses.

PMID- 11593953
TI  - Interpretation of congruent and incongruent affective communications in paranoid
      schizophrenia.
AB  - OBJECTIVES: It was hypothesized that people with paranoid schizophrenia would
      differ from depressed and normal participants in their interpretation of complex
      communications in which the affect conveyed verbally was either congruent or
      incongruent with the affect conveyed non-verbally. DESIGN: A 3 (group) x 3
      (positive, negative, neutral facial expression) x 3 (positive, negative, neutral
      verbal content) experimental design was used. There were eight participants per
      group, and the paranoid and depressed groups comprised inpatients in an acute
      psychiatric facility for either their first or second psychiatric episode.
      METHODS: Participants, tested individually, were asked to interpret the affect
      conveyed by the various communications presented. RESULTS: All participants
      interpreted most of the communications in a similar way. Paranoid schizophrenia
      patients, however, differed in their interpretation of communications in which
      negative feelings were expressed verbally. In contrast to both the normal and
      depressed groups, the paranoid schizophrenia group interpreted these
      communications as virtually devoid of any affect whatsoever. CONCLUSIONS:
      Paranoid schizophrenia patients show an information-processing bias in response
      to communications involving both congruent and incongruent negative verbal
      content. It is not obvious why the bias observed would be specific to negative
      verbal messages and not extend to negative non-verbal messages. Replication and
      further study are required.

PMID- 11593954
TI  - Social cognition and subclinical paranoid ideation.
AB  - OBJECTIVE: A number of cognitive biases have been identified relevant to
      persecutory thought (e.g. exaggerated self-serving bias). Moreover, findings of
      increased depressed mood in conjunction with high levels of self-esteem have
      contributed to theories of persecutory ideation (e.g. Bentall, Kinderman, Kaney,
      1994). Using a nonclinical sample, the present study sought to expand upon
      previous research by examining the linear relationship between persecutory
      ideation and multiple clinical and social cognitive variables. DESIGN: A cross
      sectional design was used. Correlational and multiple regression analyses were
      conducted. METHOD: One hundred and ninety-three undergraduate students were
      administered a battery of questionnaires which assessed the following domains:
      Paranoid ideation, depression, social anxiety, self-monitoring, attributional
      style and self-esteem. RESULTS: Higher levels of paranoid ideation were
      significantly associated with greater depressed mood, social anxiety and
      avoidance, evaluation apprehension, self-monitoring and lower self-esteem. There
      were no significant associations between paranoid ideation and attributional
      biases. CONCLUSIONS: These findings suggest that mood, anxiety and perceptions of
      the self are related to paranoid ideation in a nonclinical sample. These findings
      are tempered, however, by studying a nonclinical sample and the self-report
      measures of paranoid ideation that might be assessing multiple aspects of
      paranoid thought (e.g. ideas of reference).

PMID- 11593955
TI  - Effects of visuospatial tasks on desensitization to emotive memories.
AB  - OBJECTIVES: Intrusive memories of extreme trauma can disrupt a stepwise approach
      to imaginal exposure. Concurrent tasks that load the visuospatial sketchpad
      (VSSP) of working memory reduce the vividness of recalled images. This study
      tested whether relief of distress from competing VSSP tasks during imaginal
      exposure is at the cost of impaired desensitization. DESIGN: This study examined
      repeated exposure to emotive memories using 18 unselected undergraduates and a
      within-subjects design with three exposure conditions (Eye Movement, Visual
      Noise, Exposure Alone) in random, counter-balanced order. METHOD: At baseline,
      participants recalled positive and negative experiences, and rated the vividness
      and emotiveness of each image. A different positive and negative recollection was
      then used for each condition. Vividness and emotiveness were rated after each of
      eight exposure trials. At a post-exposure session 1 week later, participants
      rated each image without any concurrent task. RESULTS: Consistent with previous
      research, vividness and distress during imaging were lower during Eye Movements
      than in Exposure Alone, with passive visual interference giving intermediate
      results. A reduction in emotional responses from Baseline to Post was of similar
      size for the three conditions. CONCLUSION: Visuospatial tasks may offer a
      temporary response aid for imaginal exposure without affecting desensitization.

PMID- 11593956
TI  - Future-directed thinking in eating disorders.
AB  - OBJECTIVES: The aim of the study was to examine future-directed thinking in
      individuals with eating disorders, given the possible role of such cognitions in
      the maintenance of anorexia nervosa and bulimia nervosa. METHOD: Twenty-six
      anorexics, 18 bulimics and 34 female controls were interviewed using the 'Future
      Thinking Task', assessing quantitative and qualitative aspects of positive and
      negative anticipated events. RESULTS: Patients with anorexia nervosa had similar
      levels of positive future-oriented cognitions and significantly more negative
      future-oriented cognitions than controls. The most common positive themes in this
      group concerned the social/interpersonal and leisure/pleasure domains. The
      negative theme most commonly mentioned by anorexics was that of their own health,
      followed by the social/interpersonal domain, whereas controls were most
      preoccupied with achievement/failure and a broad range of other issues. Bulimics
      had significantly fewer positive future-oriented cognitions and significantly
      more negative future-oriented cognitions than controls, most commonly concerning
      the patient's own health. CONCLUSION: In anorexia nervosa, anticipated positive
      future outcomes may to some extent help to maintain the disorder; however, these
      patients are also highly preoccupied with the possibility of negative future
      outcomes, i.e. a failure of recovery. Bulimia nervosa sufferers are relatively
      hopeless about their future. The clinical implications of these findings are
      discussed.

PMID- 11593957
TI  - The effects of specific retrieval instruction on social problem-solving in
      depression.
AB  - OBJECTIVES: We examine the proposal that social problem-solving in depression may
      be improved with the retrieval of specific autobiographical memories. DESIGN AND
      METHODS: Social problem-solving was assessed with the Means-End Problem-Solving
      task (MEPS; Platt & Spivack, 1975a). Depressed and non-depressed participants
      were required either to retrieve a specific memory prior to generating a MEPS
      solution (primed condition) or to report on the memories retrieved during MEPS
      performance after giving their MEPS solution (non-primed condition). Participants
      also judged whether the memories retrieved had been helpful or unhelpful for the
      process of solution generation. RESULTS: In both depressed and non-depressed
      individuals, priming increased specific memory retrieval but did not improve MEPS
      performance. An interaction between depression and priming revealed that priming
      increased the retrieval of helpful memories in the depressed sample. CONCLUSIONS:
      Specificity is not, in itself, a sufficient retrieval aim for successful social
      problem-solving. However specific memory priming may be beneficial in depression
      because it facilitates the recognition of memories which are helpful for problem
      solving.

PMID- 11593958
TI  - The Challenging Behaviour Scale (CBS): development of a scale for staff caring
      for older people in residential and nursing homes.
AB  - OBJECTIVES: A review of behavioural rating scales identified the need for a
      measure of resident behaviours that staff in care homes for older people find
      difficult to manage. A 25-item, broad-based rating scale, the Challenging
      Behaviour Scale (CBS), was developed to meet this need and its psychometric
      properties were examined. DESIGN: Cross-sectional surveys. METHODS: Ratings of
      484 residents, living in 16 homes across England, were used to examine four
      methods of collecting inter-rater reliability data. Ratings of 382 residents
      living in 13 homes were used to evaluate criterion validity and to establish
      norms. Six further homes were used to explore qualitatively the validity of the
      suggested norms. Ratings of 98 residents living in four further homes were used
      to examine concurrent validity. The predictive validity of the CBS 'challenge'
      score was evaluated, using time-sampled direct observation of challenging
      behaviour in 237 residents, living in 11 homes. RESULTS: The scale records staff
      reports of the incidence, frequency and 'management difficulty' of resident
      behaviour and it can also identify 'challenging residents' through a computed
      score. It has good internal consistency, good test-retest reliability and
      adequate validity. Inter-rater reliability is good when staff receive training or
      when staff groups of at least three, of mixed qualifications, complete the scale.
      Norms are suggested for prospective studies of the prevalence of challenging
      behaviour. CONCLUSIONS: The CBS is quick to complete and may have potential for
      the evaluation of psychosocial interventions in care settings. It is, as far as
      we know, the first staff observational rating scale that is based on the reports
      of care staff, who constitute the backbone of residential care provision.
      Suggestions for improvements in criterion and content validity are outlined.

PMID- 11593959
TI  - The revised version of the Screen for Child Anxiety Related Emotional Disorders
      (SCARED-R): treatment sensitivity in an early intervention trial for childhood
      anxiety disorders.
AB  - OBJECTIVES: The revised version of the Screen for Childhood Anxiety Related
      Emotional Disorders (SCARED-R) is a recently developed self-report questionnaire
      for measuring DSM-IV defined anxiety disorder symptoms in children. The current
      study examined the treatment sensitivity of the SCARED-R. METHODS: Thirty-six
      children (aged 8-13 years) who fulfilled the criteria for generalized anxiety
      disorder, separation anxiety disorder, and/or social phobia received either group
      or individual cognitive-behavioural treatment. Children completed the SCARED-R
      and a traditional measure of childhood anxiety, the State-Trait Anxiety Inventory
      for Children (STAIC), at three points in time: (1) 6 months before treatment
      (i.e. baseline), (2) pre-treatment, and (3) post-treatment. RESULTS: Results
      showed that children's SCARED-R and STAIC scores did not change from baseline to
      pre-treatment, but significantly declined from pre-treatment to post-treatment.
      An additional finding of the present study was that group and individual CBT were
      equally effective in reducing children's anxiety symptoms. CONCLUSIONS: It can be
      concluded that the SCARED-R reliably taps treatment effects and thus should be
      regarded as a useful self-report index of childhood anxiety in clinical and
      research settings. Furthermore, the data support the notion that CBT should be
      generally regarded as an efficacious intervention for anxiety disordered
      children.

PMID- 11593960
TI  - Diagnosis of Helicobacter pylori infection by stool antigen test in southern
      Taiwan.
AB  - Helicobacter pylori (H. pylori) has been found to be associated with various
      gastrointestinal diseases. Confirmation of H. pylori infection includes invasive
      and non-invasive methods. There has been increasing interest in noninvasive tests
      recently. However, the geographical differences among H. pylori strains have been
      emphasized recently and the H. pylori strain in Taiwan showed a high cagA
      positive result and different vacA subtype when compared with those of Western
      countries. The aim of this study is to access and compare the reliability and the
      diagnostic accuracy of the stool H. pylori antigen tests by spectrophotometry and
      by the visual method, especially in Southern Taiwan. Thirty-two patients (18 men
      and 14 women; age range: 23-91 y/o, mean: 50.5 y/o) who underwent gastroendoscopy
      at Kaohsiung Medical University Hospital were enrolled in this study. H. pylori
      infection status was confirmed by culture or two positive test results on CLO
      test, histology and 13C-urea breath test (13C-UBT). The exclusion criteria
      included previous gastrointestinal tract surgery, use of antibiotics, proton pump
      inhibitor or compounds containing bismuth within 1 month of the study. Among
      them, 14 patients were with duodenal ulcer (DU), 4 with gastric ulcer (GU), 12
      with non-ulcer dyspepsia, and 2 with GU and DU. Those patients had their stool
      collected for ELISA tests of H. pylori stool antigen (HpSA). The HpSA tests were
      positive in 16 of 18 patients diagnosed as H. pylori positive, and negative in 13
      of 14 patients as H. pylori negative. The sensitivity and specificity were 88.9%
      and 92.9% respectively. The positive and negative predictive values were 94.1%
      and 86.7% respectively. The concordance of HpSA accessed by spectrophotometry and
      visual method is 100%, which makes this test even easier and cheaper. We
      concluded that stool HpSA test is a noninvasive, accurate, reliable, rapid and
      easy way to diagnose H. pylori infection in Southern Taiwan, either by
      spectrophotometry or by visual assessment.

PMID- 11593962
TI  - Arginase levels are increased in patients with rheumatoid arthritis.
AB  - Arginase and nitric oxide synthase (NOS) compete for the same substrate, L
      arginine. The reciprocal regulation of arginase and NOS in L-arginine
      metabolizing pathways has recently been demonstrated. Since NOS is involved in
      the inflammation of human arthritides, we hypothesized that this reciprocal
      regulation might also occur within the inflamed synovium. The present study shows
      that both serum arginase activity and protein levels were significantly higher in
      patients with rheumatoid arthritis (RA) than in patients with systemic lupus
      erythematosus (SLE) or osteoarthritis (OA) or in healthy controls. Arginase
      protein concentrations in supernatants of monocyte cultures from RA patients were
      also significantly higher than in those from SLE or OA patients or healthy
      controls. In RA patients, there was a significant correlation between the serum
      concentrations of arginase protein and rheumatoid factor (r = 0.82, p < 0.0001).
      These data indicate that increased arginase production is seen in RA patients,
      but not in other immune-related diseases, suggesting that increased arginase
      production is unique to, and may play an important role in, the pathogenesis of
      RA disease.

PMID- 11593961
TI  - Immunohistochemical localization of deleted-in-colon-cancer (DCC) protein in
      human epithelial, neural, and neuro-endocrine tissues in paraffin sections with
      antigen retrieval.
AB  - A gene called deleted in colon cancer (DCC) has been identified on a region of
      chromosome 18, which is deleted in 70% of colorectal cancers. The DCC gene
      encodes a protein belonging to the immunoglobulin superfamily with similarity to
      the N-CAM transmembrane proteins, and it is a putative tumor-suppressor gene.
      Alternative splicing of transcripts of transmembrane proteins, including N-CAM,
      is know to occur, resulting in different isoforms of the protein. Using a
      polyclonal antibody against the DCC gene product, we have demonstrated, by
      antigen retrieval immunostaining, the presence of a DCC protein isoform on the
      cell surface of goblet cells in the G-I tract, cytoplasm of squamous epithelium
      in the skin & esophagus and transitional epithelium in the urinary bladder,
      ductal glandular epithelium of endometrium, endocervix, prostate, gall bladder
      and breast, cytoplasm of neuron in the cerebral cortex and Purkinje cells in the
      cerebellum. In addition, we also demonstrated DCC protein expression in
      neuroendocrine cells including argentaffin cells of the stomach, small intestine,
      appendix and colon, C cells of thyroid gland, chromaffin cells of the adrenal
      gland, islets of Langerhans in the pancreas and neurons of the sympathetic
      ganglion. This restrictive distribution suggests the DCC gene products may be
      abundant expression in neuroendocrine cells of human tissue.

PMID- 11593963
TI  - The influence of professional commitment on turnover intention.
AB  - This study investigated the influence of professional commitment on turnover
      intentions of nurses. The study also examined the relationships between
      demographic data, work-related variables and the professional commitment. The
      self-administered questionnaires were distributed to one fifth of Southern
      Taiwan's population of nurses (n = 4,000). A total of 2,543 subjects completed
      the questionnaires with a 63.6% response rate. The nurses exhibited a medium-high
      degree of overall professional commitment. Age, salary, years in profession and
      years in organization were correlated significantly with professional commitment
      by Pearson's correlation. There were significant correlations between
      professional commitment and marital status, educational level, status of the
      youngest child, level of position, and family support in Spearman's correlations.
      Family support, age, level of position and status of hospital were the
      significant predictors in the final regression analysis model. The discriminant
      analysis showed that 45.4% of nursing professional commitment was correctly
      classified in predicting intention to leave the profession and 33.1% in
      predicting the intention to leave the organization. The study recommended that
      nursing professional commitment is an important moderator to affect the turnover
      intention of staff nurses.

PMID- 11593964
TI  - Two episodes of ethylene oxide poisoning--a case report.
AB  - Ethylene oxide is used as a sterilizer, a solvent, a plasticizer and in the
      manufacture of special solvents, antifreeze, polyester resins and non-ionic
      surfactants. Its toxicity is caused by an alkylating reaction with most organic
      substances in the body. Four workers, without any protection, managed the leakage
      of ethylene oxide from the collecting tank improperly on July 29, 2000. In the
      same factory, the overflow of ethylene oxide in process resulted in leakage of
      ethylene oxide again on Aug. 7, 2000. Two workers were poisoned despite wearing
      full-face respirators with ethylene oxide approved canisters. In these two
      events, the workers all smelled an ether-like odor. Six workers experienced
      nausea, vomiting, chest tightness, shortness of breath, dizziness, cough and
      ocular irritation. One worker had transient loss of consciousness. Oxygen therapy
      and supportive care were used. Patients were discharged in stable condition. The
      permissible exposure limit of ethylene oxide in air is 1 ppm as an eight hour
      TWA. Above 50 ppm, the odor threshold, a positive-pressure supplied air
      respirator is needed to protect the worker. Full-face respirators with ethylene
      oxide approved canisters could not protect our cases who smelled the odor and
      were exposed to an unknown concentration. It is important to wear positive
      pressure self-contained breathing apparatuses equipped with full facepieces to
      clean up the contamination area and rescue the patients.

PMID- 11593965
TI  - Congenital multiple plaque-like glomangiomyoma in trunk--a case report.
AB  - Congenital glomus tumor is a rare variant of glomus tumor, and glomangiomyoma is
      the least frequent histological type of glomus tumor. We present a case of
      congenital multiple plaque-like glomangiomyoma in an 11-year-old child with
      multiple diffuse plaques on his right lateral trunk. Histopathologic study showed
      a picture of typical glomus cell undergoing transition to smooth muscle cell.
      After literature review, this might be the first case report of congenital
      multiple plaque-like glomus tumor in trunk with histological appearance of a
      glomangiomyoma.

PMID- 11593966
TI  - Endometrioma in a cesarean section scar--a case report.
AB  - Scar endometriosis remains quite rare and there is only one case report in the
      literature of plastic surgery. We present a case of endometrioma appearing on the
      cesarean section scar. The classic symptom was a painful scar that became swollen
      and more tender during menstruation. The cause of surgical scar endometriosis is
      believed to be iatrogenic transplantation of endometrium to the surgical wound.
      Surgical excision remains the treatment of choice. This entity must be kept in
      mind by plastic surgeons evaluating patients who present with soft-tissue masses
      of the abdominal wall in the setting of previous combined hysterectomy and
      abdominoplasty.

PMID- 11593967
TI  - Hand-assisted laparoscopic radical nephrectomy of renal cell carcinoma--a case
      report.
AB  - A 62-year-old female patient with chronic medical history of DM and hypertension
      was admitted due to traffic accident. She was asymptomatic until 5 days before
      admission. She was referred to our medical center with an abdominal CT revealing
      left renal tumor. The diameter of the renal mass was 50 mm. On ultrasonographic
      examination, a heterogenous lesion over the left kidney was noted. Renal scanning
      showed a cold nodule in the left kidney. Hand-assisted laparoscopic
      transperitoneal radical nephrectomy was performed smoothly. The kidney was
      removed from the hand port in the supraumbilical skin incision with a volume of
      14 x 7 x 6 cm3 and weight of 570 gm. The operation time was 5 hours, blood loss
      was 200 cc, and no significant change of blood pressure was noted during the
      surgery. The patient's postoperative course was uneventful. The pathological
      report of this mass was renal cell carcinoma.

PMID- 11593968
TI  - Transluminal imaging with perspective volume rendering of computed tomographic
      angiography for the delineation of cerebral aneurysms.
AB  - Transluminal imaging with perspective volume rendering of computed tomographic
      angiography was used to investigate three patients with unruptured cerebral
      aneurysms. Selective changes in the opacity chart of computed tomography values,
      based on a spiked peak curve, represented the contour of the vessel and
      aneurysmal walls as a series of rings, and allowed a transluminal view from
      outside or inside the vessel lumen through the spaces between the rings. This
      imaging technique provided direct visualization of the underlying structures and
      an extensive perspective view of the cerebral aneurysms, including the parent
      arteries and surrounding bony structures, through the overlying vessel and
      aneurysmal walls. Transluminal imaging may be a useful method for the extra- and
      intraluminal diagnosis of a cerebral aneurysm, and for simulation of the
      interventional and surgical procedures considered for cerebral aneurysms.

PMID- 11593969
TI  - Asymptomatic brain tumor detected at brain check-up.
AB  - Brain check-up was performed in 4000 healthy subjects who underwent medical and
      radiological examinations for possible brain diseases in our hospital from April
      1996 to March 2000. Magnetic resonance imaging revealed 11 brain tumors which
      consisted of six meningiomas, three pituitary adenomas, one astrocytoma, and one
      epidermoid cyst. The detection rate of incidental brain tumor in our hospital was
      0.3%. Nine patients underwent surgery, with one case of morbidity due to
      postoperative transient oculomotor nerve paresis. The widespread use of brain
      check-up may increasingly detect asymptomatic brain tumors. Surgical indications
      for such lesions remain unclear, and the strategy for treatment should be
      determined with consideration of the patient's wishes.

PMID- 11593970
TI  - Spontaneous thrombosis of intracavernous internal carotid artery aneurysm and
      parent artery occlusion in patients with positive balloon test occlusion--two
      case reports.
AB  - Two patients with giant intracavernous internal carotid artery (ICA) aneurysms
      were intolerant to balloon test occlusion of the ICA, and later developed
      spontaneous thrombosis of the aneurysm and the parent ICA without ischemic
      sequelae. Case 1: A 60-year-old female with a giant right intracavernous ICA
      aneurysm presented with right abducens nerve paresis. An unsuccessful
      extracranial-to-intracranial bypass graft operation was complicated by transient
      postoperative ophthalmoplegia. The patient did not tolerate balloon test
      occlusion of the right ICA after attempted bypass surgery, and was treated
      conservatively. The patient presented with acute onset of headache 3 years later.
      Case 2: A 50-year-old female with a giant right intracavernous ICA aneurysm
      presented with right abducens nerve paresis. The patient was managed
      conservatively after a positive balloon test occlusion of the right ICA. The
      patient suffered transient hypopituitarism and acute onset of headache 2 years
      later. Spontaneous thrombosis of the aneurysms and occlusion of the parent ICA
      were found in both patients. Neither had major hemispheric infarcts, but the
      first patient had asymptomatic infarcts, which were presumed to be thromboembolic
      in nature. Patients with intracavernous ICA aneurysms who have positive balloon
      test occlusions appear to develop tolerance to spontaneous and gradual occlusion
      of the ICA without significant sequelae. However, these patients have an
      increased risk of developing embolic infarctions. The role for anticoagulation
      and repeat hemodynamic tests remains unclear.

PMID- 11593971
TI  - Endarterectomy for narrowing of the external carotid artery in a patient who
      underwent extracranial-intracranial bypass for occlusion of the internal carotid
      artery--case report.
AB  - A 56-year-old man had undergone extracranial-intracranial (EC-IC) bypass surgery
      for occlusion of the right internal carotid artery. Six years later, he
      complained of transient episodes of numbness in the left arm, occurring
      periodically over the previous 3 months. Neuroimaging showed the right external
      carotid artery was severely narrowed and cerebral blood flow (CBF) was diffusely
      low. Endarterectomy of the right external carotid artery was performed.
      Postoperative CBF was markedly improved, suggesting that EC-IC bypass became
      effective again by endarterectomy of a parent artery.

PMID- 11593972
TI  - Primitive trigeminal artery variant aneurysm treated with Guglielmi detachable
      coils--case report.
AB  - A 69-year-old woman had suffered from diplopia on right lateral gaze for the last
      4 months due to right abducens nerve paresis. Right carotid angiography showed a
      cavernous internal carotid artery (ICA) aneurysm of 17 x 16 x 14 mm size and a
      primitive trigeminal artery (PTA) variant supplying the territory of the
      posterior inferior cerebellar artery. Intraluminal occlusion of the aneurysm was
      performed with 15 Guglielmi detachable coils. The flow of the PTA variant and the
      ICA was preserved. Right abducens nerve paresis improved partially. PTA variant
      is a primitive artery originating from the cavernous ICA supplying the cerebellum
      without opacification of the basilar artery. Only four of the 67 cases of PTA
      variant were associated with an aneurysm of the PTA variant. The possibility of
      this rare association should be considered when treating cavernous portion
      aneurysm because of the risk of cerebellar ischemia.

PMID- 11593973
TI  - Cerebral ischemic complications following intracranial bleeding in patients with
      moyamoya disease--three case reports.
AB  - Three patients with bleeding-type moyamoya disease suffered ischemic
      complications following their first episode of intracranial bleeding. The
      patients presented with intraventricular hemorrhage and suffered cerebral
      infarction on the 14th, 16th, and 11th days after the ictus, respectively. The
      clinical records revealed no obvious hypotension before progression to infarction
      and suggested that dehydration accelerated by the administration of hyperosmotic
      drugs was a contributing factor to the infarction. Two patients underwent
      superficial temporal artery-middle cerebral artery anastomoses in the chronic
      stages and have never experienced further ischemic complications. The other
      patient died despite receiving intensive care. Hemodynamic reserve may be
      severely impaired in patients with bleeding-type moyamoya disease. Adequate
      control of hydration is important to prevent cerebral infarction after
      intracranial bleeding in patients with moyamoya disease.

PMID- 11593974
TI  - Basilar artery vasculitis secondary to sphenoid sinusitis--case report.
AB  - A 35-year-old male presented with basilar artery vasculitis secondary to sphenoid
      sinusitis manifesting as rapidly deteriorating symptoms including consciousness
      disturbance and right hemiparesis. Computed tomography (CT) on admission showed
      sphenoid sinusitis without intracranial lesion. Emergency angiography
      demonstrated basilar artery stenosis. The neurological deterioration was
      considered to be caused by ischemia of the perforating arteries branching from
      the stenotic portion of the basilar artery. The patient was treated with
      urokinase infusion through a microcatheter just proximal to the stenosis 3 hours
      after the onset of the symptoms. His consciousness level and right hemiparesis
      markedly improved immediately after the procedure. Magnetic resonance (MR)
      imaging on day 5 revealed that extension of the sphenoid sinusitis into the
      prepontine cistern had formed an abscess which was attached to the clivus. The
      basilar artery was embedded in the abscess at the angiographic stenosis.
      Cerebrospinal fluid (CSF) analysis showed white blood cell count of 601/mm3 with
      82% neutrophils, 89.2 mg/dl protein, and 31 mg/dl glucose. No causative organism
      in the CSF could be identified by smear or culture. Early MR imaging and CSF
      examination are recommended when patients present with both ischemic symptoms
      involving the basilar artery and opacification of the sphenoid sinus on CT to
      identify basilar artery vasculitis secondary to sphenoid sinusitis.

PMID- 11593975
TI  - Transcondylar fossa approach to treat ventral foramen magnum meningioma--case
      report.
AB  - A 41-year-old female presented with a meningioma of the craniocervical junction
      manifesting as tetraparesis and vesicourethral dysfunction. Neuroradiological
      examinations showed a homogeneous enhanced mass lesion extending from the foramen
      magnum to the upper aspect of the second vertebral body. The tumor was totally
      removed via the transcondylar fossa approach, which is one type of the lateral
      approach. She was discharged without neurological deficits. The transcondylar
      approach is often utilized for lesions that occupy the ventral portion around the
      foramen magnum. The transcondylar fossa approach, a variation of the
      transcondylar approach, is a refined technique which obtains a closely similar
      surgical working field. Use of the transcondylar fossa approach remains
      controversial when treating patients with little brain stem dislocation, a small
      condylar fossa, and a protruding occipital condyle, but the approach can easily
      be converted to the transcondylar approach. The transcondylar fossa approach
      could become a standard method to access the craniocervical junction.

PMID- 11593976
TI  - Interhemispheric cyst causing leg monoparesis in the elderly--case report.
AB  - A 64-year-old female presented with a rare case of interhemispheric cerebral cyst
      manifesting as progressive monoparesis in the right lower extremity for 2 years.
      Surgical excision of the cyst wall was performed and communication to the
      subdural space was created. Postoperatively, the cyst was greatly reduced in
      size, and the neurological signs and symptoms were markedly improved.
      Interhemispheric cyst often presents with motor disturbances such as hemisparesis
      or paraparesis. These symptoms tend to progress slowly and sometimes years are
      required for a proper diagnosis. Interhemispheric cyst can also cause slowly
      progressive monoparesis in the lower extremity.

PMID- 11593977
TI  - Modified draping to avoid fluid leakage in cranial surgery--technical note.
AB  - Contamination under draping due to leakage of fluid from the surgical field
      should be avoided to maintain cleanness. A modified draping method was developed
      using standard draping materials but with an irrigation pouch applied directly to
      the scalp. The present method prevents fluid leakage along the scalp, increases
      surgeon comfort, and reduces postoperative room cleaning.

PMID- 11593978
TI  - A new detection algorithm for implantable cardioverter defibrillator.
AB  - One of the most important subsystems of implantable cardioverter defibrillator
      (ICD) is the sensing stage, since it determines the sensitivity and specificity
      of the device to detect the heart rate and the underlying arrhythmia. This paper
      aims to investigate a new detection algorithm for ICD, which operates fully
      automatically. The algorithm ARGUS was implemented as a computer model and tested
      with intracardiac electrograms recorded (band-pass: 0.05 to 500 Hz; sampling
      rate: 1-4 kHz) under different rhythm condition like sinus rhythm (n = 18),
      atrial tachycardia (n = 16), and ventricular tachycardia as well as fibrillation
      (n = 139) during electrophysiological tests or ICD implantation. The results of
      the tests were visually inspected on a beat-to-beat basis. In total 31,934 events
      were classified by the algorithm (18,758 as long intervals (LI) with cycle length
      > 300 ms; 13,176 as short intervals (SI)). 195 out of the 13,176 SI and 572 out
      of 18,758 LI were incorrectly classified (SI: 1.48%; LI: 3.05%). In conclusion
      the new algorithm yield high sensitivity (99.9%) and specificity (97.0%) as known
      from conventional ICD algorithms but need no manual adjustments.

PMID- 11593979
TI  - Polygraphic belt with force-sensing expander for physiological tests on
      cosmonauts.
AB  - To study cardiorespiratory and neuromotor functions in cosmonauts a novel belt
      with embedded polygraphic sensors and a force sensing expander were developed.
      The sensors are: a three-electrode ECG/impedance plethysmographic system to
      capture cardiac and respiratory activity, two triaxial accelerometers to record
      limb micromotions and an IR reflex-sensor to detect peripheral pulse waves. The
      expander consists of an elastic cable in series with a load cell to measure the
      extension force and to adjust the extensions by visual feedback. The cable
      stiffness was chosen rather high (150-200 N/m) in order to induce involuntary
      limb oscillations at higher extension levels. The equipment was tested in MIR
      spaceflights and is projected for physiological tests on the ISS.

PMID- 11593980
TI  - The effect of an addition of sodium hydrogenphosphate to poly(D,L)lactide-
      results of in vitro examinations.
AB  - Aim of the study was to examine the influence of sodium hydrogenphosphate (NaP)
      on the pH value and the mechanical characteristics of degrading poly(D,L)lactide
      (PDLLA). Test rods of PDLLA with or without NaP amounting to 1, 10, 25 or 50 mol
      per 100 mol lactate, the degradation product of PDLLA, were produced by injection
      molding. Molecular weight and bending strength of the rods were measured before
      and after an accelerated in vitro-test (55 degrees C, Ringer's solution (RS)).
      For a long-time degradation test PDLLA-rods with or without 1 mol% NaP were
      placed in RS or Soerensen buffer solution (SB, pH 7.4) at 37 +/- 1 degrees C.
      Measurements of pH and determination of length, volume and weight of the samples
      were done in 2-4 week intervals up to the 52nd week after incubation. A pH-drop
      was measured in RS or SB containing pure PDLLA after 28 or 36 weeks respectively.
      Stabilization of the pH value due to admixed NaP delayed the degradation related
      pH drop for 8 weeks in RS or SB. A strong increase of length, volume and weight
      was measured in PDLLA + NaP-rods. In conclusion minimal stabilization of pH but
      also an increase of outer dimensions of the samples was found due to the
      admixture of NaP to PDLLA. Thus, an addition of substantially higher amounts than
      1 mol% NaP in PDLLA can not be recommended, regardless of the positive effects on
      pH stabilization.

PMID- 11593981
TI  - [Muscle efficiency in total shoulder prosthesis implantation: dependence on
      position of the humeral head and rotator cuff function].
AB  - Modern shoulder prostheses permit an anatomic reconstruction of the joint,
      although the biomechanical advantages are not proven. The goal of this study was
      to investigate the relationship between position of the humeral head and function
      of the shoulder prosthesis (muscle efficiency). Shoulder elevation-motion and
      rotator cuff defects were simulated in vitro in a robot-assisted shoulder
      simulator. The EPOCA Custom Offset shoulder prosthesis (Argomedical AG, Cham, CH)
      was implanted in seven normal shoulders (77 +/- 20 kg, 55 +/- 14 years). Active
      elevation was simulated by hydraulic cylinders, and scapulothoratic motion by a
      specially programmed industrial robot. Muscle efficiency (elevation-angle/muscle
      force of the deltoid muscle) was measured in anatomic (ANA), medialised (MED) and
      lateralised (LAT) positions of the humeral head, with or without rotator cuff
      muscle deficiency. Medialisation increased efficiency by 0.03 +/- 0.04 deg/N (p =
      0.022), lateralisation decreased it by 0.04 +/- 0.06 deg/N (p = 0.009).
      Supraspinatus muscle deficiency increased the deltoid force required to elevate
      the arm, and thus decreased efficiency (ANA p = 0.091, MED p = 0.018, LAT p =
      0.028). The data confirm that the position of the humeral head affects the
      mechanics of total shoulder arthroplasty. Medialisation increases efficiency of
      the deltoid muscle and may prove useful in compensating isolated supraspinatus
      muscle deficiency. Lateralisation, in contrast, leads to an unfavorable
      situation.

PMID- 11593982
TI  - [Evaluating the stability of fracture fixation systems: mechanical device for
      evaluation of 3-D stiffness in vitro].
AB  - Different fixation systems are used for fracture and defect treatment. A
      prerequisite for complication free healing is sufficient mechanical stability of
      the osteosynthesis. In vitro investigations offer the possibility of both
      analysing and assessing the pre-clinical fixation stability. Due to the complex
      loading environment in vivo, stiffness analysis should include a complete
      determination of the stiffness under standardised conditions. Based on a
      mathematical procedure to calculate the 3-D stiffness, a mechanical testing
      device for the 3-D loading of fixation systems was designed and integrated in the
      existing test set-up. The set-up consisted of a material testing machine to
      produce the necessary loads and an optical measurement device to detect the
      resulting inter-fragmentary movements. To validate the testing device, the 3-D
      stiffness matrices of different Ilizarov fixator configurations were determined
      and compared. The good reproducibility of the test was reflected in the small
      intra-individual variability of the stiffness components. A distinct direction
      dependence of the fixator stiffness was observed. Increasing the number of rings
      led to a stiffness increase of up to 50%, especially in bending. The presented
      testing device allows a complete standardised determination of the stiffness of
      different fixation systems. It considers the direction dependence of the
      stiffness and creates a prerequisite for a more direct implant comparison.

PMID- 11593983
TI  - [Identification of wear particles of joint prostheses in tissues using laser
      microprobe mass analysis (LAMMA)].
AB  - The definite identification of wear particles from joint prostheses is of great
      importance for the development of joint replacement, as the type and quantity of
      different wear particles gives information on the wear resistance of implant
      materials. From the types of prostheses nowadays in use polyethylene wear of the
      sockets, bone cement wear, metallic and ceramic wear can be generated. Whereas
      polyethylene wear can be easily identified by its bright luminescence in
      polarized light and its characteristic configuration, the distinction of the
      small granular wear particles of the bone cement, metal and ceramic by light
      microscope is difficult. The laser microprobe mass analysis (LAMMA) is a method,
      which allows the analysis of single light microscopically detectable wear
      particles in tissues. Not only contrast medium particles of the bone cements
      (zirconium oxide or barium sulfate) but also metallic and aluminum oxide
      particles could be definitely identified within the pseudocapsules as well as in
      regional lymph nodes by LAMMA-analysis, whereby the bone cement wear
      predominated. In addition, the distinction between organic substances (as blood
      degradation products), which may appear similar to wear particles in
      configuration and colour, and the foreign material is also possible with this
      method.

PMID- 11593984
TI  - Timing of analog research in medicinal chemistry.
AB  - Analog research plays an important role in medicinal chemistry. Having identified
      a new target in molecular biology many similar lead compounds are synthesized
      resulting in closely related products on the market. Another approach is the
      further optimising of an existing drug in order to improve on the original. In
      some cases these two approaches overlap. The question of timing and the
      importance of analog research are analyzed in this paper.

PMID- 11593985
TI  - Novel thrombin inhibitors with azaphenylalanine scaffold.
AB  - In this paper the synthesis and antithrombotic activity of a series of novel
      thrombin inhibitors with azaphenylalanine scaffold are described. By systematic
      structural modifications for this series we have identified optimal groups for
      achieving nanomolar potency, that led to potent inhibitors of thrombin with Ki
      values up to 11 nM.

PMID- 11593986
TI  - beta-Lactam derivatives as enzyme inhibitors: derivatives of (E)-2-[(RS)-1-(4
      methoxyphenyl)-2-oxo-4-phenylazetidin-3-ylidene]propionic acid.
AB  - The 1,4-diaryl disubstituted azetidin-2-one (beta-lactam) 1 is transformed into
      the 3-methylidene derivative (E)-2-[(RS)-1-(4-methoxyphenyl)-2-oxo-4
      phenylazetidin-3-ylidene]propionic acid (3), and then, using the DCC/NHS method
      reacted with amino acid esters and dipeptide esters forming 3-(peptidyl)-beta
      lactams 5 and 7. Structures and properties are evaluated mainly by spectroscopic
      methods and discussed. As molecular modeling experiments might suggest a
      potential activity as inhibitors of PPE(HLE), a number of selected compounds has
      been tested in an enzyme assay. But none of them showed any remarkable inhibitory
      activity. Evaluation of the data was done with the new program EnKinPlot.

PMID- 11593987
TI  - Synthesis and antibacterial activity of 5- and 6-hydroxy substituted 4
      aminoquinolines and derivatives.
AB  - The synthesis and antimicrobial activity of 4-amino-8-methylquinolines 8, 11
      substituted with a hydroxy- or methoxy-group at 5- and at 6-position have been
      investigated. The title compounds could be prepared by a six-step procedure
      according to the literature starting from commercially available anilines 1. The
      novel 4-aminoquinolines 8,11 exhibited slight antibacterial activity against Gram
      positive and Gram-negative bacteria.

PMID- 11593988
TI  - [Ring cleavage of N-methoxypyridinium salts by amines].
AB  - The 3- and 4-cyano-1-methoxypyridinium salts 1 and 2 reacted with primary and
      secondary, aliphatic and aromatic amines via ring cleavage to the 5-aminopenta
      2,4-dienaloxime ethers 3-10, which were examined concerning their
      stereochemistry. Contrary to literature no uniform all-trans type products
      resulted, but the ring opened compounds 3, 4, 7 and 8 contained a cis double bond
      due to the initial cyclic compound. Partially the corresponding configuration
      isomers differed only slightly in the energy contents and according to the
      solvent an equilibrium was observed. Therefore the configuration of the products
      seems to depend sensitively on the reaction parameters.

PMID- 11593989
TI  - A stability-indicating proton nuclear magnetic resonance spectroscopic method for
      the analysis of propantheline bromide in pharmaceutical samples.
AB  - A rapid, specific and accurate proton nuclear magnetic resonance (1H NMR)
      spectroscopic method was developed for the simultaneous quantitative analysis of
      propantheline bromide and its degradation product, xanthanoic acid, in bulk
      materials and tablets. 1,3,5-Trinitrobenzene served as an internal standard and
      deuterochloroform was used as the solvent for the analytical samples. The
      quantities of propantheline bromide and xanthanoic acid were calculated on the
      basis of the integrals for signals of the methine proton of propantheline at 5.09
      ppm, the methine proton of xanthanoic acid at 4.99 ppm, and the aromatic protons
      of the internal standard at 9.39 ppm. The accuracy of the method was established
      through the analysis of synthetic mixtures containing the parent compound, its
      degradation product and the internal standard. An excellent agreement was
      verified between the assay results and the quantities of the various compounds in
      the mixtures. The mean +/- SD recovery values for propantheline bromide and
      xanthanoic acid from a set of 10 synthetic mixtures were 99.6 +/- 0.8% and 98.9
      +/- 1.8%, respectively. The assay of 10 lots of commercial propantheline bromide
      tablets by 1H NMR spectroscopy indicated drug and degradate contents in the
      ranges 97.1-99.8% and 0.1-0.9%, respectively. In addition, the proposed
      analytical method was found suitable for detecting the formation of xanthanoic
      acid from propantheline bromide in aqueous media in concentrations below 0.1% of
      that of the parent compound.

PMID- 11593990
TI  - [Protein analysis of enzyme tablets].
AB  - Enzyme tablets with butyrylcholine esterase (CHE) and peroxidase (POD) partly
      lose enzymatic activity during compaction at a pressure of 495 MPa. Compared to
      solutions of the original enzyme, no changes of ultraviolet absorbance and
      fluorescence intensity in the tablet solutions were found. Only small changes
      were observed in the far ultraviolet circular dichroism spectra. Neither missing
      nor additional bands were detected with polyacrylamide gel electrophoresis.
      Heated (150 degrees C) solid starting material with CHE and POD showed still part
      of its original enzymatic activity. The ultraviolet absorbance increased with
      continued heating until precipitation occurred. The circular dichroism spectra
      are changed clearly.

PMID- 11593992
TI  - Time-controlled release pseudoephedrine tablets: bioavailability and in vitro/in
      vivo correlations.
AB  - In chronopharmacotherapy, circadian changes in disease symptoms are taken into
      account. Press-coated, time-controlled release tablets containing pseudoephedrine
      hydrochloride as a model drug have been formulated and the suitability of this
      highly soluble drug in relation to the new drug delivery system was evaluated.
      Hydroxypropylmethylcellulose was used in the coat of the tablet to adjust drug
      release. If such a formulation was administered in the evening it would have
      maximal effect in the early morning, and would be useful for the treatment of
      nocturnal symptoms. Two cross-over, single-dose bioavailability studies were
      carried out on eight healthy volunteers. A dissolution test method was developed
      to establish level A and level C in vitro/in vivo correlation for four
      formulations. With a low viscosity grade of polymer, peak concentrations were
      achieved after five hours. The drug was absorbed much more slowly from tablets
      containing a high viscosity grade polymer, with a plasma peak at ten hours. For
      further development of the drug delivery system described, a dissolution test
      method at pH 7.2 at a rotation speed of 150 min-1 is recommended on the basis of
      level A in vitro/in vivo correlation.

PMID- 11593991
TI  - Transdermal absorption of phytoestrogens.
AB  - The transdermal absorption of the isoflavones, daidzein and genistein, applied on
      the skin in olive oil was studied in vivo. The concentrations of the isoflavones
      and their metabolites were monitored in plasma and urine by GC-MS methods. It was
      found that the concentration of genistein in plasma was 3-fold higher than the
      plasma concentration of daidzein. In contrast, daidzein excretion was 2-3-fold
      higher than that of genistein in urine. The excretion rate of the studied
      phytoestrogens in urine and their concentration in plasma was significantly
      decreased after repeated transdermal application. The urinary recovery of
      administered daidzein and genistein after the first application was 15.9% and
      7.7%, respectively and this dropped to 1.6% and 0.7% after the second
      application. The results obtained might suggest that daidzein and genistein are
      captured in the skin following repeated transdermal application.

PMID- 11593993
TI  - Design and in vitro evaluation of a mucoadhesive oral delivery system for a model
      polypeptide antigen.
AB  - A novel mucoadhesive drug carrier system has been generated which protects a
      model polypeptide antigen from degradation by the most abundant intestinal
      proteases. The enzyme inhibitors antipain, chymostatin and elastatinal,
      respectively, were covalently attached to the mucoadhesive polymer sodium
      carboxymethylcellulose (NaCMC) and the inhibitory efficacy of the resulting
      polymer-inhibitor conjugates was evaluated in vitro. When these inhibitor
      conjugates were combined with the thiolated polymer polycarbophil-cysteine (PCP
      Cys), 95.8 +/- 3.8% (mean +/- SD, n = 3) of the incorporated model antigen
      ovalbumin (OVA) was protected from enzymatic degradation within 90 min incubation
      in the presence of an artificial intestinal fluid containing the pancreatic
      serine proteases trypsin, chymotrypsin and elastase. Replacing the CMC-inhibitor
      conjugates in the dosage form by unmodified CMC significantly reduced the
      protective effect to 78.8 +/- 4.7% (mean +/- SD, n = 3), whereas incorporation of
      the model antigen in a CMC dosage form omitting PCP-Cys protected 72.5 +/- 3.2%
      (mean +/- SD, n = 3) of OVA from degradation within a 90 min incubation period.
      Further, the incorporation of PCP-Cys resulted in higher cohesiveness within the
      dosage form and controlled drug release of the antigen for a time period of more
      than 9 h. Results suggest that a delivery system combining thiolated polymer and
      polymer-inhibitor conjugates improves the metabolic stability of the model
      polypeptide antigen and may therefore be a useful tool for oral protein
      vaccination.

PMID- 11593994
TI  - Influence of adjuvants on the dissolution profile of tablets containing high
      doses of spray-dried extract of Maytenus ilicifolia.
AB  - A 2(3) factorial design was used in order to evaluate the influence of some
      adjuvants on the dissolution profile of tablets containing high doses of Maytenus
      ilicifolia spray-dried extract. Tablets were prepared on a single punch tablet
      press using 15 mm flat punches by individual direct compression of 650 mg from
      each formulation containing 375 mg of the spray-dried extract. The factors
      investigated were disintegrant (croscarmellose sodium or sodium starch
      glycolate), lubricant (colloidal silicon dioxide or magnesium stearate) and
      filler/binder (microcrystalline cellulose or lactose). The dissolution profiles
      were analyzed to determine the dissolution kinetics, the dissolution half-lives
      (t50%), the similarity factor (f2) and the dissolution efficiency (DE %), which
      was selected as the response criteria to evaluate the factorial design. The
      results revealed that in spite of the high content of spray-dried powder in the
      tablets, the dissolution profiles of the extract did depend on the adjuvant used.
      The filler/binder had the most important effect on the dissolution efficiency of
      the tablets.

PMID- 11593995
TI  - Solubilization of bromhexine hydrochloride in aqueous lecithin dispersions.
      Physicochemical characterization of interactions between drug and carrier.
AB  - In aqueous systems bromhexine hydrochloride (Br-HCl) has a poor solubility (4.54
      mg/g) and displays no amphiphilic character e.g. self association. Therefore the
      drug is molecularly dispersed in water until the solubility product of Br-HCl is
      exceeded. Solubilization of Br-HCl is linearly increased on addition of lecithin;
      calculations show that 10 mg Phospholipon 90G (P 90G) enable solubilization of
      additional 1.25 mg Br-HCl after the solubility product of Br-HCl has been
      exceeded. This means that four to five phospholipid molecules are needed for the
      solubilization of one drug molecule. Ternary systems with P 90G concentrations up
      to 20% have a lamellar microstructure. The systems are multilamellar vesicle
      dispersions as polarisation microscopy, transmission electron microscopy and
      small-angle X-ray diffractometry suggest. Furthermore, Br-HCl solubilization
      leads to a significant reduction of the interlamellar distance d and increases
      the elastic properties of the systems. 31P NMR data provide evidence that Br-HCl
      is solubilized within the lipophilic part of the phospholipid bilayer.

PMID- 11593996
TI  - Oxidation of lovastatin in the solid state and its stabilization with natural
      antioxidants.
AB  - Oxidative instability of the hydroxy methylglutaryl Co-A reductase inhibitor
      lovastatin in the solid state and stabilization with natural antioxidants
      (ascorbic acid, rutin, gallic acid, quercetin and caffeic acid) was investigated.
      Lovastatin in the solid state and binary mixtures with 10% (w/w), 25% (n/n),
      12.5% (n/n) and 6.3% (n/n) of each of the antioxidants were prepared. Oxidation
      experiments were performed on the scanning calorimeter using dynamic oxygen
      atmosphere. The amount of non-oxidized lovastatin was determined using HPLC. The
      results of the experiments have shown that lovastatin is unstable to oxidation
      under higher temperatures and in the presence of oxygen, and that some
      antioxidants markedly stabilize the drug. The most significant antioxidative
      effect was seen with caffeic acid and rutin, followed by gallic acid and
      quercetin. Ascorbic acid was only moderately effective. The results prove that
      flavonoids do have significant antioxidative potential. This phenomenon can be
      used to improve oxidative stability of drugs such as lovastatin which are
      sensitive to the presence of oxygen.

PMID- 11593998
TI  - Synthesis and cytotoxicity of 1-phenyl-3,3-diacetoxy-1-propene.

PMID- 11593997
TI  - Structurally related immunological effects of triterpenoid saponins.
AB  - The influence of the triterpenoid saponins 1-10 has been investigated on murine
      spleenocytes in the lymphocyte transformation test and on murine macrophages in
      an phagocytosis assay. The lymphocyte transformation test and the phagocytosis
      assay showed that the tested compounds have no stimulating effect. However, a
      significant inhibition of lymphocyte proliferation by the triterpenoid saponins
      2, 6 and 10 was demonstrated.

PMID- 11593999
TI  - [Nitramine analogues of ibuprofen].

PMID- 11594000
TI  - Sustained drug delivery system based on a cationic polymer and an anionic
      drug/cyclodextrin complex.

PMID- 11594001
TI  - Renin-angiotensin system inhibitors--implications in the metabolism of the
      reactive oxygen species.

PMID- 11594002
TI  - Antioxidant activity of rhamnazin-4'-O-beta-[apiosyl(1-->2)] glucoside in the
      brain of aged rats.

PMID- 11594003
TI  - [Clinical and microbiological study of adult periodontal disease].
AB  - The aim of this study was to carry out a microbiological evaluation of sites with
      and without clinical evidence of moderate and severe periodontitis and their
      correlation with clinical parameters. A total of 52 disease sites and 10 healthy
      sites were selected according to clinical criteria. The following clinical
      indexes were measured for all the sites: plaque index, gingival index, blood on
      probing, depth on probing and insertion level. Samples of subgingival plaque were
      collected for culture and for differential counts of microbial morphotypes. In
      disease sites the most frequently isolated were: Prevotella intermedia/nigrescens
      (65%), Porphyromonas gingivalis (23%), Actinobacillus actinomycetemcomitans
      (23%), Fusobacterium nucleatum (10%) and Peptostreptococcus sp. (31%). The
      aerobic gram-positive microflora was predominant in healthy sites. Significant
      differences were observed in microbial morphotypes between healthy and disease
      sites: cocci 18.71% and 78.90%, motile rods 46.12% and 16.70%, total spirochetes
      26.48% and 2.80%, respectively. The presence of motile rods, spirochetes and P.
      intermedia/nigrescens were the parameters with most sensitivity to suspect
      periodontal disease. There were significant differences in the subgingival
      microflora between healthy and disease sites in patients with moderate and severe
      periodontitis.

PMID- 11594004
TI  - [Typing and evaluation of hydrocarbon-degrading activity of a bacterial strain
      isolated from the Bahia Blanca estuary, Argentina].
AB  - During screening for oil-degrading bacteria in sediments of Bahia Blanca estuary,
      a bacterial strain was isolated which uses a limited number of organic compounds,
      especially lineal hydrocarbons. The goals of this study were to characterize the
      strain and to evaluate its activity on crude oil. Based on phenotypic
      characteristics and the analysis of 16S rDNA sequences, it was determined that
      the strain is strongly related to Alcanivorax borkumensis. The strain was
      cultured, under quasicontinuous conditions, with crude oil as sole source of
      carbon and energy. After 30 days of incubation, n-alkane decrease reached 86%.
      The isoalkanes pristane and phitane were degraded more slowly, but a decrease of
      about 63% was obtained. The strain studied would be useful for the bioremediation
      of the local coasts, so that this study will be continued in order to obtain its
      successful application in the environment.

PMID- 11594005
TI  - [Streptococcus pneumoniae: evolution of antibiotic resistance in a pediatric
      hospital in Cordoba, Argentina].
AB  - The wide variety of prevalence of antimicrobial resistant Streptococcus
      pneumoniae in different countries confirms the importance of determining local
      patterns of resistance. From 1992 to 2000, we studied the pattern of
      antimicrobial resistance in S. pneumoniae and its evolution along the years,
      using 468 strains isolated in the Hospital de Ninos de Cordoba. A total of 177
      isolates (37.8%) were not susceptible to penicillin, with 19% intermediate and
      18.8% resistant strains. High and intermediate resistance levels to cefotaxime
      were 4.9% and 10.9%, respectively. Decreased susceptibility to
      trimethoprim/sulfamethoxazole (TMS), erythromycin, chloramphenicol, and rifampin
      was found in 194 isolates (41.5%), 32 (6.8%), 13 (2.8%) and 3 (0.6%),
      respectively. No isolates resistant to vancomycin were detected. The most
      commonly combined resistance patterns were: penicillin/TMS (35.6%) and
      penicillin/TMS/cefotaxime (11.8%). This study highlights the increased rate of
      drug resistant S. pneumoniae during the last years, and the importance of
      antimicrobial resistance surveillance of adequate empirical therapy involving
      local and regional susceptibility patterns.

PMID- 11594006
TI  - Theiler virus-GDVII strain (TMEV-GDVII) infection of cultured astrocytes. An
      image analysis of its effects on cell activation.
AB  - Our original aim was to determine whether dBcAMP-induced activation of cultured
      astrocytes affected the course of subsequent viral infection. After 2 h exposure
      of 2-day-old first subculture of mouse astrocytes to dBcAMP 1 mM, cell monolayers
      grown in glass coverslips of Leighton tubes were inoculated with 10(3) PFU of
      Theiler virus-GDVII strain (TMEV-GDVII). At 9 days post-infection (pi), viral
      infectivity persisted in supernatants from dBcAMP-treated cultures, but was no
      longer detectable in non-stimulated controls. The relatively spared astroglial
      monolayer at day 1 pi, hardly affected by progressive viral cytolytic effect, was
      chosen for immunolabeled cell count, whether by viral antigen or GFAP. To this
      end, 20 fields for each coverslip were digitalized at 250x final magnification.
      In dBcAMP treated cultures, viral antigen(+) cells were fewer and lower in
      percentage versus infected cultures lacking stimulation. As regards GFAP
      staining, stimulation or infection per se induced a greater number and percentage
      of labeled astrocytes. According to morphometric characterization, such increase
      was due to a greater number of process-bearing astrocytes. It may be concluded
      that, regardless of previous dBcAMP treatment, early TMEV-GDVII infection
      enhanced immunocytochemical and morphological differentiation in cultured
      astrocytes.

PMID- 11594007
TI  - [Molecular characterization of autochthonous clinical isolates of Histoplasma
      capsulatum var. capsulatum using RAPD-PCR].
AB  - The aim of our work was to determine the genotypic relatedness among H.
      capsulatum isolates from Argentinian patients with or without AIDS and isolates
      from other sources and geographic origins. We analyzed band patterns of 16
      isolates obtained by RAPD-PCR, 11 Argentinian clinical isolates (8 from patients
      with AIDS and 3 from patients without AIDS), 2 strains from the CDC, 2 isolates
      from Mexico and one isolate from Uruguay. With the band patterns obtained, we
      built a dendrogram, which showed 3 major groups. Group I contained 2 isolates
      from Mexico, group II 1 strain from CDC and group III included 13 isolates, and
      was divided into 4 subgroups. Subgroup IIIa contained 2 isolates from patients
      with and without AIDS. Subgroup IIIb included isolates from patients without AIDS
      from Chaco. Subgroup IIIc contained 7 isolates from Argentina (from Buenos Aires
      province) and the Uruguayan isolate (6 isolates from patients with AIDS).
      Subgroup IIId included only one strain from CDC. All the Argentinian and the
      Uruguayan isolates went into group III, subgroups IIIa, IIIb and IIIc. This is a
      preliminary study; however, a relatedness of the RAPD-PCR band patterns and the
      geographic origin was observed. Although there might be a probable association
      between immunocompromised patients with AIDS and infective capability of some H.
      capsulatum isolates, further studies with a larger number of isolates from
      different sources and geographic origins are necessary to confirm these results.

PMID- 11594008
TI  - [Cryptosporidium y Giardia in surface water].
AB  - The aim of this work was to determine Giardia and Cryptosporidium levels in
      surface water used either as recreational or drinking water source, and to
      estimate the relationship with bacteriological and physicochemical parameters
      determining water quality. This study was carried out during 22 months, in Santa
      Fe and Santo Tome cities (Santa Fe Province, Argentina). Cryptosporidium from
      100% of the recreational samples (44-2404 oocysts/100 l) and from 92% of water
      sources (< 20-539 oocysts/100 l) was detected, while Giardia was found in lower
      concentrations and frequencies: 72% (< 20-670 cysts/100 l) and 31% (< 20-65
      cysts/100 l), respectively. Statistically significant relationships were found
      between these parasites and organic matter, turbidity and bacteriological
      indicators of contamination (Escherichia coli, streptococci, Enterococcus spp,
      Pseudomonas aeruginosa). These relationships, however, vary according to the
      sampling place, the source and levels of contamination.

PMID- 11594009
TI  - [Utility of prolonged incubation and terminal subcultures of blood cultures from
      immunocompromised patients].
AB  - The value of blind terminal subcultures (7 and 30 days) and prolonged incubation
      (30 days) of blood cultures from immunosuppressed patients was analyzed in the
      Fundacion Favaloro, the Fundacion para la Lucha contra las Enfermedades
      Neurologicas de la Infancia and the Hospital de Ninos Ricardo Gutierrez. A total
      of 2707 blood cultures and 369 patients were included (transplantation of solid
      organs 154, oncohematologic disorders 106 and solid tumors 109). Bact-Alert
      bottles were incubated at 35 degrees C for 30 days in the Bact-Alert System.
      Bottles with positive signals were routinely removed, and aliquots of the broth
      were Gram stained and subcultured aerobically in chocolate agar and Sabouraud
      agar. A total of 136 bacteremic episodes were obtained. The positivization time
      of blood cultures was 81.6% at 24 h, 93.3% at 48 h, 94.5% at 72 h and 97.7%
      within 7 days. Only 3 (2.2%) episodes were positive by blind terminal subcultures
      and 1 (0.75%) by prolonged incubation (14 days). The median time and range of
      positivization in hours were 13.8 and 2.2-168, respectively. The microorganisms
      isolated were coagulase negative staphylococci (n = 24), Klebsiella pneumoniae (n
      = 22), Staphylococcus aureus (n = 21), Escherichia coli (n = 18), Acinetobacter
      spp (n = 9), Candida spp (n = 8), Pseudomonas aeruginosa (n = 6), Enterobacter
      cloacae (n = 5), Stenotrophomonas maltophilia (n = 5), Enterococcus faecalis,
      Salmonella spp and Capnocytophaga sputigena (n = 2), Enterobacter aerogenes,
      Enterococcus faecium, Citrobacter diversus, Candida albicans, Klebsiella oxytoca,
      Chryseomonas luteola, Serratia marcescens, Abiotrophia spp, Campylobacter jejuni,
      Moraxella catarrhalis, Moraxella urethralis, Neisseria sicca, beta hemolytic
      group G streptococci, Rhodococcus equi, Micrococcus spp, Cryptococcus neoformans
      and Streptococcus mitis (n = 1). In our experience, blind terminal subcultures
      and prolonged incubation of blood cultures from immunosuppressed patients are
      unnecessary and cost expensive.

PMID- 11594010
TI  - [HTLV-I/II seroprevalence and risk factors associated with infection in a blood
      donor population in Cordoba, Argentina].
AB  - In this study we have determined the seroprevalence of infections by HTLV-I/II in
      the blood donor population from the city of Cordoba. A total of 5476 blood donor
      sera were screened for HTLV-I/II antibodies by particle agglutination assay (PA)
      (SERODIA HTLV-I, Fujirebio INC, Tokyo, Japan). The reactive sera samples were
      confirmed by an "in house" indirect immunofluorescence assay (IFA). 14 out of
      5476 blood donors studied were PA reactive and were confirmed positive by IFA,
      showing a prevalence of 0.26% (95% confidence interval: 0.126%-0.394%). All the
      positive samples, except one, met the criteria for HTLV-I. Although one HTLV-I
      infected donor was an intravenous drug abuser and two donors were born in highly
      endemic areas for HTLV-I, no specific risk factors were identified among the
      others. The demonstration that HTLV-I circulates in blood donor population of
      Cordoba, points out that the systematic screening of blood for HTLV-I/II
      antibodies must be implemented in the blood banks, in an attempt to prevent the
      spread of infections with this oncogenic virus in Argentina.

PMID- 11594011
TI  - The challenges to intimacy and sexual relationships for gay men in HIV
      serodiscordant relationships: a pilot study.
AB  - Human Immunodeficiency Virus (HIV) infection and disease progression create
      imbalance in long-term, HIV-serodiscordant, gay male relationships, particularly
      in sexual relations and issues of physical and emotional intimacy. Stage of
      disease progression and worldview of the couple both affect the relationship and
      its survival. To redress imbalance, partners employ a range of coping strategies
      and techniques. This article explores these issues in the context of HIV
      serodiscordant gay couples and how they preserve their relationships in the face
      of these unique challenges. For workers who provide psychotherapeutic and
      community support for people with HIV and for their partners, the results of this
      study may be helpful in recognizing stress factors for couples, and tailoring
      support services to the needs of both partners. Overall, this study provides a
      basis for further work examining the dynamics of serodiscordant relationships.

PMID- 11594012
TI  - Secondary traumatic stress, psychological distress, sharing of traumatic
      reminiscences, and marital quality among spouses of Holocaust child survivors.
AB  - In this study, we examined the issue of secondary traumatic stress (STS) among
      spouses of Holocaust survivors who were children during the World War II. STS is
      defined as comprising the same components as posttraumatic stress disorder
      (PTSD), except that the person evidencing the symptoms has not actually been
      exposed to the traumatic event(s), but has developed them as a result of caring
      for someone with PTSD. Participants were 90 couples who completed self-report
      questionnaires regarding posttraumatic symptoms, psychological distress, and
      marital quality. The results showed that about one-third of the spouses suffered
      from some degree of STS symptoms. Secondary traumatic stress symptoms and
      psychological distress among spouses were significantly related to hostility,
      anger, paranoia, and interpersonal sensitivity in the survivor, but unrelated to
      whether the survivor had shared his/her reminiscences with the spouse. Female
      spouses were found to suffer more distress than male spouses, especially when
      their partner suffered high levels of PTSD. The results suggest that STS is, to a
      large degree, related to the demands of living with a symptomatic survivor,
      possibly more than to the empathic element thought to be central to this
      syndrome.

PMID- 11594013
TI  - Ten adaptive strategies for family and work balance: advice from successful
      families.
AB  - Despite negative media images and social dynamics insensitive to the lives of
      many dual-career couples, research shows that these families are largely healthy
      and thriving. In this study, we investigated the adaptive strategies of middle
      class, dual-earner couples (N = 47) with children that are successfully managing
      family and work. Guided by grounded-theory methodology, analysis of interview
      data revealed that these successful couples structured their lives around 10
      major strategies: Valuing family, striving for partnership, deriving meaning from
      work, maintaining work boundaries, focusing and producing at work, taking pride
      in dual earning, prioritizing family fun, living simply, making decisions
      proactively, and valuing time. Each adaptive strategy is defined and illustrated
      through the participants' own words. Clinical applications for therapists working
      with dual-earner couples are offered.

PMID- 11594014
TI  - Beyond enmeshment: evidence for the independence of intrusiveness and closeness
      caregiving in married couples.
AB  - In a 1996 article on family theory, we (Green & Werner) proposed that family
      enmeshment should not be equated with high cohesion and that the construct of
      enmeshment fails to discriminate between two distinct relationship processes:
      Closeness-caregiving and intrusiveness. In this study, our model of these two
      independent dimensions of family connectedness was tested by assessing spouses
      from 264 couples, using the California Inventory for Family Assessment (CIFA).
      The CIFA scales showed acceptable reliability. Significant interspouse validity
      correlations also were obtained. As predicted by our theory, factor analyses
      distinguished dimensions of intrusiveness (blurring of boundaries) from
      dimensions of closeness-caregiving (such as warmth and nurturance). On all but
      two factors, behaviors of only one spouse (but not of both) had interpretable
      loadings. That is, in most areas, the two spouses' behaviors did not load
      together to form meaningful factors. The latter finding suggests that family
      systems theory--with its central notion of reciprocally contingent behaviors
      between family members--may be useful in understanding only a few dimensions of
      spouses' behavior (such as reciprocal aggression) whereas personality-in-context
      theories may be better for understanding most other dimensions (such as warmth
      and nurturance).

PMID- 11594015
TI  - Making sense in conversations about learning disabilities.
AB  - This article describes an integrative, multisystem clinical approach to the
      psychological and relational problems that develop around learning disabilities.
      Positioned in relationships with children, families, and schools, the therapist
      addresses the emotions, interpersonal conflicts, and problematic beliefs that
      contribute to problems. Using clinical skills to contain and relieve painful
      emotions, the therapist soothes "inflammation at the boundaries" of relationships
      among children, families, and schools, depolarizing conflicts within and between
      systems. Familiar with developmental and educational psychology and developmental
      neurobiology, the therapist makes this specialized knowledge intelligible to
      children, families, and teachers. This article describes two specific methods,
      the chart of strengths and weaknesses and the map of learning functions, which
      facilitate communication of specialized knowledge about children with learning
      disabilities. The therapist uses expert knowledge to help members of the
      treatment system transform blaming, helpless, or hopeless interpretations of the
      problem into more hopeful constructions, which support healthy development.

PMID- 11594016
TI  - AAMFT Master Series tapes: an analysis of the inclusion of feminist principles
      into family therapy practice.
AB  - Content analysis of 23 American Association for Marriage and Family Therapy
      Master Series tapes was used to determine how well feminist behaviors have been
      incorporated into "ideal" family therapy practice. Feminist behaviors were
      infrequent, being evident in fewer than 3% of time blocks in event sampling and
      10 of 39 feminist behaviors of the Feminist Family Therapist Behavior Checklist.
      These eminent therapists most often dealt with empowerment of male clients and
      management of power differentials in the therapeutic relationship in a relatively
      feminist manner, but they tended to hold women responsible for family issues,
      endorsed traditional rather than egalitarian relationships, and overlooked how
      the social context affects families. Several of the therapists were blatantly
      sexist in their treatment of female clients, communicating disrespect of and
      pathologizing them. The few tapes portraying effective incorporation of feminist
      principles in family therapy indicate that a handful of behaviors are key to this
      approach.

PMID- 11594017
TI  - Comparisons of marriage and family therapists, psychologists, psychiatrists, and
      social workers on job-related measures and reactions to managed care in Iowa.
AB  - This study compares marriage and family therapists (MFTs) to psychologists,
      psychiatrists, and social workers on job-related measures, such as job autonomy,
      job satisfaction, burnout, and intention to stay in their present position, as
      well as on reactions to a managed care initiative in the state of Iowa. Findings
      indicate that MFTs scored significantly lower than other practitioners on job
      autonomy and intention to stay in their present position, but there were no
      differences in job satisfaction or burnout. Marital and family therapists also
      reported less dissatisfaction with the managed care initiative than
      psychiatrists, although virtually all practitioners were dissatisfied with the
      managed-care program. These findings indicate some dissatisfaction within the MFT
      profession and may be relevant to practitioners seeking to change or expand their
      practice, as well as to the needs of MFTs in their training programs.

PMID- 11594018
TI  - Marriage and family therapists evaluate managed mental health care: a qualitative
      inquiry.
AB  - This study examined the experiences of 26 marriage and family therapists working
      in managed mental health care. A qualitative strategy was used to explore
      therapists' perspectives regarding practice in a managed care environment. Using
      an open-ended, semi-structured, mailed questionnaire four themes emerged from the
      data. These are the adaptations of clinical practice, issues of treatment
      duration/abandonment, effects of managed care on the therapeutic relationship,
      and issues of diagnosis. Recommendations are drawn from the findings and
      discussed.

PMID- 11594019
TI  - When approved is not enough: development of a supervision consultation model.
AB  - The dramatic increase in the literature that addresses family therapy training
      and supervision over the last decade has been predominantly in the area of
      theory, rather than practice. This article describes the development of a meta
      supervisory learning context for approved supervisors and provides examples of
      interactions between supervisors that subsequently influenced both therapy and
      supervision. We delineate the assumptions that inform our work and offer specific
      guidelines for supervisors who wish to implement a similar model in their own
      contexts. We provide suggestions for a proactive refiguring of supervision that
      may have profound effects and benefits for supervisors and supervisees alike.

PMID- 11594020
TI  - Postmodernism in marriage and family therapy training: doctoral students'
      understanding and experiences.
AB  - The purpose of this study is to advance our understanding of how doctoral
      students perceive postmodernism's influence in the field of Marriage and Family
      Therapy (MFT). According to the literature, postmodernism has had a profound
      impact on many fields, including MFT. However, tracking of how postmodernism is
      actually being rendered in theory, research, practice, and training warrants
      investigation. This study utilized focus group interviews to investigate the
      perceptions of MFT doctoral students. Findings suggest that while participants
      are attracted to postmodern tenets, they also report feeling a mixture of
      liberation and excitement with confusion and fear regarding how postmodernism is
      influencing MFT models of therapy.

PMID- 11594021
TI  - Do we really understand? An experiential exercise for training family therapists.
AB  - This paper presents an experiential exercise for training beginning marriage and
      family therapists, as well as several adaptations of the format. The basic
      exercise consists of role playing a therapy session in which the people playing
      the clients speak a language that is not understood by the therapist-in-training.
      Although the therapist cannot understand the clients, the clients can understand
      the therapist. This exercise assists students to become more cognizant of the
      need to be cautious and curious in the cocreation of meaning in therapy. In
      addition, this exercise builds confidence and clinical skills, such as learning
      about nonverbal communication while observing process.

PMID- 11594022
TI  - Comparative sensitivity of three populations of the cladoceran Moinodaphnia
      macleayi to acute and chronic uranium exposure.
AB  - Assessment of differences in the response of three different populations of the
      tropical cladoceran Moinodaphnia macleayi to uranium exposure was evaluated. The
      populations tested included a laboratory stock (maintained for 10 years), a wild
      population collected from Bowerbird Billabong (an uncontaminated environment),
      and a population collected from Djalkmara Billabong (a relatively contaminated
      environment with elevated levels of uranium), located on the Ranger uranium mine
      site, Jabiru East, NT, Australia. Chronic and acute toxicity of uranium was
      determined for all three populations. The no-observed-effect-concentration (NOEC;
      reproduction) and lowest observed-effect-concentration (LOEC; reproduction) for
      uranium ranged between 8-31 micrograms L-1 and 20-49 micrograms L-1,
      respectively, for all three populations. The 48 h EC50 (immobilization-lethality)
      for uranium ranged between 160-390 micrograms L-1 for all three populations.
      There was little difference in the response of the three populations of M.
      macleayi to acute and chronic uranium exposure, although the response of the
      laboratory population to chronic uranium exposure appeared more variable than the
      "wild" populations. There was no apparent tolerance in the population of M.
      macleayi obtained from Djalkmara Billabong when exposed to elevated levels of
      uranium. M. macleayi was significantly more sensitive to uranium exposure than
      other species previously tested. It was concluded that the sensitivity of the
      laboratory population (to uranium) is still representative of natural M. macleayi
      populations.

PMID- 11594023
TI  - The cross-sectional study of the health effects of occupational exposure to
      carbon disulfide in a Chinese viscose plant.
AB  - This article presents results of carbon disulfide exposure assessment in a
      Chinese viscose rayon factory and represents the cross-sectional study beginning
      phase of the occupational epidemiological project. The authors measured external
      exposure levels to carbon disulfide at a Chinese viscose rayon factory and
      monitored results as internal exposure indexes by testing urine samples of
      workers exposed to carbon disulfide levels. The rate at which carbon disulfide is
      metabolized by exposed subjects was demonstrated by 2-thio-thiazolidine-4
      carboxylic acid (TTCA) concentrations in urine of exposed subjects, which was
      studied to determine best time points for internal exposure sampling. Carbon
      disulfide concentrations in the air of the workplace were analyzed with gas
      chromatography with flame photometric detector (GC-FPD); presence of TTCA in
      urine samples of subjects was determined using a modified high-performance liquid
      chromatography method. Kinetics of TTCA excretion was studied by analysis at
      different time points during and after exposure of workers to carbon disulfide. A
      total of 155 personal samples were obtained. Carbon disulfide concentration at
      staple viscose hall was found to be 13.72 +/- 1.12 mg/m3 in terms of geometric
      mean and geometric standard deviation. Carbon disulfide concentration at filament
      spinning hall was found to be 20.05 +/- 1.33 mg/m3. TTCA values of subjects at
      staple spinning hall were 1.18 +/- 0.43 and 1.07 +/- 0.38 mg/g creatinine for
      subjects working at filament spinning hall. The best time for TTCA sampling is at
      the end of the exposure-working shift.

PMID- 11594024
TI  - Tests for the toxicity assessment of cyanobacterial bloom samples.
AB  - Cyanobacterial (blue-green algal) blooms are one of the common consequences of
      the increasing eutrophication of surface waters. The production of cyanobacterial
      toxins and their presence in drinking and recreational waters represents a
      growing danger to human and animal health. Due to a lack of toxin standards and
      to resource limitations on the wide-scale use of analytical methods (e.g., high
      performance liquid chromatography, enzyme-linked immunosorbent assay (ELISA)) in
      cyanobacterial toxin monitoring, it is necessary to assess and to develop
      additional methods for their detection and estimation. Microbiotests using
      invertebrates offer a possible approach for the inexpensive and straightforward
      detection and assessment of cyanobacterial bloom toxicity. Three microbiotests
      with: Thamnocephalus platyurus, Daphnia magna, and Spirostomum ambiguum were
      examined with bloom samples containing hepatotoxic microcystin-LR and up to five
      additional microcystin variants. Two kinds of cyanobacterial bloom sample
      preparations were tested: crude extracts (CE) and purified extracts (PE). The
      highest toxicity was found when CE was used for microbiotests. The sensitivity of
      microorganisms decreased from S. ambiguum to T. platyurus and to D. magna. A
      statistically significant correlation was found between microcystin concentration
      and T. platyurus biotest, and between mouse bioassay and S. ambiguum results.
      Addition of Me2SO (1%, v/v) is a possible method to increase the sensitivity of
      the microorganisms for microcystin-LR.

PMID- 11594025
TI  - Extraction and purification of the zwitterions cylindrospermopsin and
      deoxycylindrospermopsin from Cylindrospermopsis raciborskii.
AB  - The hepatotoxin cylindrospermopsin (CYN) has been isolated from the
      cyanobacterium Cylindrospermopsis raciborskii (C. raci.). Efforts to study this
      toxin have been hampered by the time-consuming requirement to extract it from
      cultures of the organism. It is usually extracted from lyophilized cells
      collected from a laboratory culture. Our preliminary work suggested far more of
      the toxin is available in solution in the culture media than in the cells
      collected. We have therefore investigated the use of commercially available solid
      phase extraction sorbents to extract CYN from culture media in which C. raci. has
      been grown. A range of reverse phase and ion-exchange sorbents were tested across
      a range of pHs for their ability to retain CYN without success. Subsequently,
      graphitized carbon cartridges were found to retain CYN strongly. Elution with 5%
      formic acid in methanol allowed the CYN to be regained for final purification by
      HPLC. Deoxy-CYN, an analog of CYN can also be extracted using this procedure.

PMID- 11594026
TI  - Development of a field bioassay for the side-effects of herbicides on vascular
      plants using Brassica napus and Poa annua.
AB  - A field bioassay method has been developed for assessing side-effects of
      herbicides on Brassica napus and Poa annua. The test method aims at effects
      outside the target area, up to 20 m from the treated parcel. Experiments were
      conducted in the field and in a glasshouse with the herbicides atrazin,
      bentazone, diquat, glyphosate, and r(4-chloro-2-methylphenoxyacetic acid) MCPA.
      An iterative procedure was used with the aim of developing a sound test
      procedure. The resulting method appeared to be very sensitive. Pesticide drift
      was measured using water-sensitive paper. Effects were sometimes found below the
      detection limit of this method (at 8 m from the treated parcel with moderate wind
      speeds of 3-5 m/s). The sensitivity of the test and the test conditions are
      discussed and an optimized method is presented.

PMID- 11594027
TI  - Cell-free protein synthesis inhibition assay for the cyanobacterial toxin
      cylindrospermopsin.
AB  - The cyanobacterial toxin cylindrospermopsin (CYN) is known to be a potent
      inhibitor of protein synthesis. This paper describes the use of a rabbit
      reticulocyte lysate translation system as a protein synthesis inhibition assay
      for CYN. A dose response curve for protein synthesis inhibition by CYN was
      constructed and was modeled to a sigmoidal dose response curve with variable
      slope (R2 = 0.98). In this assay, CYN has an IC50 of 120 nM [95% confidence
      limits (Cl) = 111-130 nM] with a detection limit in the region of 50 nM in the
      assay solution. Application of the assay allows quantification of toxin samples
      within the range 0.5-3.0 microM (200-1200 micrograms/L) CYN. To assess the
      usefulness of this assay, a range of toxic and nontoxic Cylindrospermopsis
      raciborskii extracts, including both laboratory strains and environmental
      samples, were assayed by protein synthesis inhibition. These CYN quantifications
      were then compared to quantifications obtained by high performance liquid
      chromatography (HPLC) and HPLC-tandem mass spectrometry (HPLCMS-MS). The results
      demonstrate that the protein synthesis inhibition assay correlates well with both
      HPLCMS-MS (r2 = 0.99) and HPLC (r2 = 0.97) quantifications. We conclude that this
      is an accurate and rapid assay for the measurement of cylindrospermopsin in
      cyanobacterial extracts.

PMID- 11594028
TI  - Identification of genes implicated in toxin production in the cyanobacterium
      Cylindrospermopsis raciborskii.
AB  - Cylindrospermopsis raciborskii is a bloom-forming cyanobacterium found in both
      tropical and temperate climates which produces cylindrospermopsin, a potent
      hepatotoxic secondary metabolite. This organism is notorious for its association
      with a significant human poisoning incident on Palm Island, Australia, which
      resulted in the hospitalization of 148 people. We have screened 13 C. raciborskii
      isolates from various regions of Australia and shown that both toxic and nontoxic
      strains exist within this species. No association was observed between
      geographical origin and toxin production. Polyketide synthases (PKSs) and peptide
      synthetases (PSs) are enzymes involved in secondary metabolite biosynthesis in
      cyanobacteria. Putative PKS and PS genes from C. raciborskii strains AWT205 and
      CYP020B were identified by PCR using degenerate primers based on conserved
      regions within each gene. Examination of the strain-specific distribution of the
      PKS and PS genes in C. raciborskii isolates demonstrated a direct link between
      the presence of these two genes and the ability to produce cylindrospermopsin.
      Interestingly, the possession of these two genes was also linked. They were also
      identified in an Anabaena bergii isolate that was demonstrated to produce
      cylindrospermopsin. Taken together, these data suggest a likely role for these
      determinants in secondary metabolite and toxin production by C. raciborskii.

PMID- 11594029
TI  - Testing the toxicity of influents to activated sludge plants with the Vibrio
      fischeri bioassay utilising a sludge matrix.
AB  - To protect the bioceonosis within activated sludge, a method of predicting the
      toxic effect of influents to the biological treatment stage of waste water
      treatment plants, based on DIN method 38412 L 34, has been developed. A
      population of the luminescent marine bacterium Vibrio fischeri was incorporated
      into a sludge testing matrix derived from a model laboratory and real activated
      sludge plants. The sludge was challenged with different concentrations of pure
      toxicants and complex aqueous samples, and light output by V. fischeri monitored.
      The results were compared to toxicant testing in the absence of sludge (standard
      test). The modified method was found to be less sensitive for some toxicants
      tested than the standard DIN and other bioluminescent tests, but considered more
      realistic as it provides buffering and takes into account sorption which can
      affect the sensitivity of the test towards some compounds. The method is
      comparable in terms of ease of use, speed, reproducibility and cost effectiveness
      to standard V. fischeri luminescence methods.

PMID- 11594030
TI  - Effects of Cu+2 and pH on the fitness of Ceriodaphnia dubia (Richard 1894)
      (Crustacea, Cladocera) in microcosm experiments.
AB  - An important disturbance of anthropogenic origin frequently occurring in
      freshwater ecosystems is a rise in the concentration of heavy metals in solution,
      among which copper stands out due to its known toxicity. However, the study of
      the chemical behavior of copper in solution is highly dependent on pH. In this
      study, the effect of ionic copper on the fitness of Ceriodaphnia dubia was
      assessed in microcosm experiments under different conditions of Cu+2 and pH. Two
      groups of experiments were conducted: effects on survival and fecundity, and
      effects on population dynamics. In the former, both pH and copper concentrations
      were manipulated. On the other hand, only the concentration of biologically
      available ionic copper was manipulated whereas pH was maintained constant in the
      population dynamics experiments. There was an agreement between both sets of
      experiments in terms of their results, showing important toxic effects of copper
      as evidenced through significant differences between controls and treatments in
      survival and fecundity. Mean age of first reproduction was delayed, and both the
      number of neonates produced per female and number of broods decreased with the
      increase in the concentration of copper. R0 was always lower at pH 6 than at pH 8
      and was negatively related to the increment in the concentration of copper under
      either pH. A significant effect on population dynamics at 5 micrograms l-1 of
      copper sulfate was found and the extinction of the population at 20 micrograms l
      1 of copper sulfate. New values of toxicity from copper are proposed, and the
      potential effects that an increment in copper could have on the communities that
      occupy a central position in aquatic food webs are discussed.

PMID- 11594031
TI  - Effect of zinc and benzalkonium chloride on Nitrosomonas communis and potential
      nitrification in soil.
AB  - A bacterial contact assay is described which uses a chemoautotrophic
      microorganism, Nitrosomonas communis (strain Nm2) to evaluate the biological
      effect of contaminated soils. The effects of two toxicants on the ammonium
      oxidation activity of the autochthonous microbial population in the soil are
      compared with inhibition of the same biological response in the new monospecies
      bioassay. Experiments were performed using soil samples dosed with organic and
      inorganic contaminants (benzalkonium chloride and zinc) to demonstrate the mode
      of operation and the sensitivity of the bioassay. The EC50 values of zinc and
      benzalkonium chloride were calculated to be 171 and 221 mg kg-1 soil,
      respectively. The toxic response provided by the bioassay can thus predict the
      effect of soil pollutants on the autochthonous nitrifying bacteria.

PMID- 11594032
TI  - The toxicities of a polyunsaturated fatty acid and a microcystin to Daphnia
      magna.
AB  - Polyunsaturated fatty acids (PUFAs) are essential components of zooplankton
      diets. However, studies with PUFAs from cyanobacteria indicate toxic properties.
      We investigated the toxicity of the PUFA gamma-linolenic acid and the
      cyanobacterial peptide toxin microcystin-LR to Daphnia. The PUFA was acutely
      toxic at a concentration of 9 micrograms ml-1. The effect of microcystin-LR was
      not statistically significant at the concentration used (3 micrograms ml-1), but
      an additive effect with the PUFA was observed. Relative to LC50-values of well
      known pollutants, the PUFA was intermediately toxic. The activity equaled that of
      microcystin-LR, which is commonly treated as one of the most potent
      cyanobacterial toxins. Our results suggest that the toxic properties of PUFAs
      deserve more attention.

PMID- 11594033
TI  - Pink snapper (Pagrus auratus) as a bioindicator of aquatic. Environmental health
      in Western Australia.
AB  - Pink snapper (Pagrus auratus), an endemic Western Australian fish species, was
      tested for its potential as a bioindicator of aquatic environmental health. Mixed
      function oxygenase (MFO) induction (as a biomarker of exposure), and sorbitol
      dehydrogenase (SDH) activity (as a biomarker of liver damage) were of special
      interest to the study as these biochemical tools have not been validated for any
      Western Australian fish species. Juvenile pink snapper were injected
      intraperitoneally (i.p.) with 0, 10, 100, 500, and 1000 micrograms PCB-126 per
      kilogram. Fish were sacrificed 10 days postinjection, and livers and blood
      samples were collected for MFO and SDH analysis, respectively. Doses of 10 and
      100 micrograms PCB-126 per kilogram caused the highest MFO induction, while doses
      of 0 and 1000 micrograms PCB-126 per kilogram did not result in higher MFO
      activity relative to carrier-injected control fish. SDH activities were not
      significantly different among treatments indicating that hepatocellular damage
      was not responsible for the reduced MFO activity at the highest dose. The result
      of the study demonstrates that pink snapper may potentially be used as a
      bioindicator species in Western Australia when MFO is used as a biomarker.

PMID- 11594034
TI  - Cancer research in the 21st century.

PMID- 11594035
TI  - Isolation of disease-associated genes through genome analysis and their clinical
      application.

PMID- 11594036
TI  - Development of new surgical treatments in spinal surgery: expansive open-door
      laminoplasty and percutaneous nucleotomy.
AB  - The outstanding achievements of two renowned spine surgeons, who are alumni of
      the Department of Orthopaedic Surgery, Keio University, are described. Anterior
      decompression followed by fusion and laminectomy had been the standard techniques
      for cervical myelopathy due to disc herniation, spondylosis and ossification of
      the posterior longitudinal ligament. However, both techniques were not without
      certain comorbidities. Dr. Kiyoshi Hirabayashi devised an epoch-making expansive
      open-door laminoplasty, in which both sufficient posterior decompression and
      preservation of cervical stability are achieved simultaneously with reduced risk
      of such complications. Dr. Sadahisa Hijikata is the pioneer of a totally new
      concept treatment, percutaneous nucleotomy, for lumbar disc herniation, one of
      the most prevailing diseases that cause low back pain and sciatica. He devised
      this technique to avoid prolonged conservative treatment with associated
      suffering of the patients and to minimize the chance of morbidity that is
      occasionally associated with an open surgery. This technique, together with
      chemonucleolysis, has led to the establishment of intradical or intermediate
      treatments which lie between conservative and surgical treatments. Both
      techniques have not only brought the relief of pain and suffering in numerous
      patients, but have also opened the door to the development of many new modified
      procedures and technologies. Most importantly, these two techniques still remain
      as the most viable choice among various similar modifications. The rationale,
      indictions, technique as well as the present status and future perspective for
      these two innovative yet fundamental techniques are introduced and discussed.

PMID- 11594037
TI  - Percutaneous coronary intervention: current perspective.
AB  - More than 20 years have passed since percutaneous transluminal coronary
      angioplasty (PTCA) was introduced for the treatment of coronary artery disease.
      During the first decade, PTCA outcome had improved significantly. However, acute
      occlusive complications and restenosis remained as significant limitations of the
      procedure. During the second decade, new procedures, such as stents and
      atherectomy (directional coronary atherectomy, and Rotablator) had been
      introduced and had a significant impact on the outcome of percutaneous coronary
      intervention (PCI). In addition to the improvements in the equipment, the use of
      glycoprotein IIb/IIIa inhibitors to prevent platelet aggregation has reduced
      procedure-related complications. PCI continues to evolve with new developments
      such as distal protection devices to prevent distal embolism, brachytherapy and
      drug-eluting stents to prevent restenosis. These new technologies may play a
      significant role in expanding the applications of PCI in the future.

PMID- 11594038
TI  - Leeds-Keio artificial ligament: a new concept for the anterior cruciate ligament
      reconstruction of the knee.
AB  - The features of the Leeds-Keio artificial ligament, which was developed as a
      collaborative project between the University of Leeds in the UK and Keio
      University, are introduced. The ligament is made of polyester, and has a mesh
      structure. The diameter of the polyester fibers is 22 microns. The ligament has a
      tensile strength sufficient for anterior cruciate ligament (ACL) reconstruction,
      and fatigue tests have shown satisfactory durability of the ligament. The
      stiffness of the Leeds-Keio artificial ligament is about 200 N/mm, which is
      similar to the natural ACL. A combination of a bone plug and stapling is used for
      the bone fixation, taking into consideration the strength in both the initial
      mechanical fixation and the long term fixation. From an animal study, it was
      shown that fibrous tissue was induced around the artificial ligament, and the
      collagen fibers became aligned in the longitudinal direction of the ligament. For
      the clinical experience, one-hundred and thirty five cases were reviewed. The
      Lachaman sign disappeared in 87.4%, and the pivot shift sign disappeared in
      88.1%. Side-to-side difference of anterior displacement of the knee, measured
      with a KT-2000 knee arthrometer at 30 degrees of flexion, was less than 3 mm in
      85.9%. More than 90% of the patients experienced full range of motion. Thus, from
      the clinical results, it can be concluded that reasonable stability was obtained
      with the operation. If the Leeds-Keio artificial ligament may not be the perfect
      substitute for the ACL, both experimental and clinical studies indicate that it
      represents a major forward step in the history of knee ligament surgery.

PMID- 11594039
TI  - Development of endoscopic surgery for the minimally invasive treatment of
      digestive and other diseases.
AB  - Minimally invasive surgery has rapidly changed the performance of surgical
      practice in a wide range of surgical specialities in the last decade of the 20th
      century. The marked progress in endoscopic surgery has been conducted especially
      in general and digestive surgery. The Department of Surgery, School of Medicine,
      Keio University has contributed to the development and establishment of
      endoscopic surgery in every subspeciality of general and digestive surgery. Our
      achievements include the development of original methods for laparoscopic wedge
      gastrectomy and endoscopic thyroidectomy, establishment of surgical techniques in
      endoscopic surgery for esophageal, gastric, colorectal and hepatobiliary
      diseases, and the introduction of robotics and tele-communicative technologies to
      endoscopic surgery.

PMID- 11594040
TI  - Sudden death due to cardiovascular disorders: a review of the studies on the
      medico-legal cases in Tokyo.
AB  - The Tokyo Metropolitan Government has a medical examiner system, in which all
      cadavers classified as "unusual death" in the city of Tokyo should be examined,
      and if necessary, autopsied to determine the cause of death. Of about 10,000
      unusual deaths examined per year, two thirds are usually determined to have died
      of natural causes. The most common cause of sudden natural death is ischemic
      heart disease, especially acute myocardial infarction. Pathological examination,
      however, proves acute myocardial ischemia in only one third of autopsies.
      Subarachnoid hemorrhage and intracerebral hemorrhage, acute myocarditis and
      cardiomyopathies and aortic dissection/aneurysm as well as pulmonary
      thromboembolism are frequent causes of death in medical examiner cases. Both
      pathological and socio-medical problems associated with these diseases are
      discussed.

PMID- 11594041
TI  - Inhibition of nitric oxide production during global ischemia ameliorates ischemic
      damage of pyramidal neurons in the hippocampus.
AB  - We examined the relationship between nitric oxide (NO) production and delayed
      neuronal death (DND), in the rat hippocampus induced by 21 minutes of transient
      global ischemia produced by the occlusion of both of the common carotid arteries
      combined with systemic hypotension. NO production during ischemia and reperfusion
      was investigated by quantifying the nitrite (NO2-) levels of the in vivo
      microdialysis samples collected ever 3 minutes from the hippocampus. To determine
      the origin of NO production, we studied the effects of the focal administration
      of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the constitutive NO
      synthase (NOS). We also carried out systemic administration of a selective
      neuronal NOS inhibitor, 7-nitroindazole (7-NI). Rats were grouped as follows:
      group 1 (n = 22), vehicle; group 2 (n = 19), L-NAME; group 3 (n = 12), 7-NI; and
      group 4 (n = 12), a sham operation. The role of NO in the hippocampal DND was
      investigated histologically one week after ischemia. The level of NO production
      was significantly decreased in groups 2 and 3 as compared to group 1 in which NO
      production was significantly increased (p < 0.05). The density of remaining
      neurons in the CA1 area was significantly reduced only in group 1 (p < 0.01).
      Taken together, it can be concluded that NO production by neuronal NOS during
      ischemia and reperfusion resulted in DND in the CA1 region of the rat
      hippocampus.

PMID- 11594042
TI  - Newer skin signs of systemic disease.
AB  - The skin is a well-known reflection of internal disease states. It provides the
      astute clinician with clues that lead to the diagnosis of systemic illness. While
      skin disease is rarely life-threatening, serious morbidity and mortality may be
      avoided by early recognition of subtle cutaneous signs signaling internal
      problems. The recent literature was reviewed to glean new findings that either
      added new associations to older syndromes or described completely new diseases.
      While entire books are written regarding the "Skin Signs of Internal Disease",
      this article focuses only on the newest of such findings.

PMID- 11594044
TI  - The depression dilemma. When the "baby blues" turns into much more.

PMID- 11594043
TI  - Developmental changes and ocular dominance plasticity in the visual cortex.
AB  - There is a shift in ocular dominance of cells recorded in the visual cortex which
      occurs after closure of one eye during a critical period lasting from eye opening
      to puberty. Three criteria distinguish factors that are crucially related to
      ocular dominance plasticity: 1) the factor should be more concentrated or active
      at the peak of the critical period; 2) dark rearing, which makes the cortex less
      plastic early in the critical period and more plastic late in the critical
      period, should have a similar effect on the factor, and 3) antagonists or
      inhibitors of the factor should block ocular dominance plasticity. The second
      criterion can be used to distinguish activity-related factors that may simply
      increase or decrease with development from factors that are more specifically
      related to plasticity. Two factors currently fulfill these criteria, namely N
      methyl-D-asparate (NMDA) receptors and protein kinase A (PKA). PKA and NMDA
      receptors are linked through calcium, since calcium influx through the NMDA
      receptor increases the production of cyclic AMP by calcium-sensitive adenylate
      cyclase, which in turn activates PKA. PKA is specifically involved, since protein
      kinase G and protein kinase C antagonists do not inhibit ocular dominance
      plasticity. However, NMDA agonists and PKA activators by themselves are not known
      to bring back plasticity. Thus there may be two or more pathways for ocular
      dominance plasticity acting in parallel with each other: for example,
      metabotropic glutamate receptors may act in parallel with NMDA receptors to
      change calcium levels within the cell.

PMID- 11594045
TI  - Increasing mammography screenings among African Americans.

PMID- 11594046
TI  - Case of the month. Aberrant placement of central venous catheter in a thymic
      vein.

PMID- 11594048
TI  - Cationic dye-sensitized degradation of sodium hyaluronate through photoinduced
      electron transfer in the upper excited state.
AB  - The formation of ground-state complexes of methylene blue (MB) and thionine (TN)
      with sodium hyaluronate (NaHA) was clearly observed by means of absorption
      spectra in aqueous solution. Irradiation of the complexes using 313 nm light
      caused significant degradation of NaHA under oxygen and argon. However, the use
      of visible light over 400 nm, which gives the lowest excited singlet state of the
      cationic dyes, caused no degradation. MB and TN were more efficient sensitizers
      for the degradation of NaHA than rose bengal (RB), although RB is a more
      efficient singlet oxygen (1O2) sensitizer than the cationic dyes. Under similar
      conditions the polysaccharides with carboxyl groups, such as alginic acid and
      polygalacturonic acid, also photodecomposed. However, the polysaccharides without
      carboxyl groups, such as pullulan and methyl cellulose, did not. The irradiation
      of the polysaccharides in the presence of powdered titanium dioxide as a
      photocatalyst to generate the hydroxyl radical (.OH) in aerated aqueous solution
      caused the fragmentation of all the polymers. It was confirmed that methyl
      viologen, an electron-accepting sensitizer, formed a charge-transfer complex with
      NaHA, the irradiation of which caused the efficient degradation of NaHA. In the
      presence of beta- and gamma-cyclodextrins the MB- and TN-sensitized
      photodegradation of NaHA was markedly suppressed. This was probably due to the
      formation of the inclusion complexes comprising the cationic dyes and the
      cyclodextrins. On the basis of the results obtained we propose that the cationic
      dye-sensitized degradation of NaHA involves a photoinduced electron-transfer
      process between the upper excited dyes and the ground-state NaHA and that .OH and
      1O2 do not participate in the degradation.

PMID- 11594049
TI  - Competition between vibrational relaxation and photochemistry: relevance of
      vibronic quantum effects.
AB  - Two molecules showing photochemistry but no fluorescence have been investigated
      at 80 K in a rigid matrix regarding the behavior of the quantum yield for bond
      fragmentation as a function of the vibrational/vibronic level and electronic
      excited state. A new equation was developed to determine the photochemical
      quantum yield under ambient conditions (80 K). The levels/bands involved were
      those within a given vibrational progression, in different progressions as well
      as in combination. The yield was low (phi = 0.1) with excitation into the n = 0
      level of S1 but very rapidly increased with excitation into higher levels whether
      they were harmonics or combination levels. A parallel result was observed upon
      excitation into S2. Vibrational relaxation/deactivation occurs only between
      levels of the same vibrational progression. Deactivation from the 0 level of S2
      does not occur via levels of S1. The photochemically active modes correspond to
      the vibrational modes present in the region of the molecule where bond breakage
      occurs. These results add further proof of the complex nature and number of
      processes that can occur within excited states of photochemically active
      molecules.

PMID- 11594047
TI  - Prevention of respiratory syncytial virus infection in high risk infants.
AB  - The incidence of serious RSV illness in premature infants and in infants with CLD
      can be reduced. Prophylaxis in infants with CHD and cystic fibrosis seem prudent
      as well, and clinical trials are currently under way to evaluate the use of
      Synagis in these high-risk groups. Synagis is preferred for most high-risk
      children because of its ease of administration, safety and effectiveness. The
      dose for Synagis is 15 mg/kg i.m. monthly during RSV season.

PMID- 11594050
TI  - Electrocyclic rearrangement of pentamethylcyclooctapyrimidine-2,4-diones:
      reaction pathway into a 9,11-diazapentacyclo-[6.4.0.0(1,3).0(2,5).0(4,8)]dodecane
      system and a 9,11-diazapentacyclo [6.4.0.0(1,3).0(2,6).0(4,8)]dodecane system.
AB  - Photolysis of 6-chloro-1,3-dimethyluracil and mesitylene in the presence of
      trifluoroacetic acid (TFA) at low temperature gave 1,3,5,7,9- and 1,3,6,8,10
      pentamethylcyclooctapyrimidine-2,4-diones (1b, 1c). Sequential photoreaction of
      the former (1b) resulted in the formation of 9,11
      diazapentacyclo[6.4.0.0(1,3).0(2,5).0(4,8)]dodecane-2,4-dione (2b) by way of 9
      exo-methylene derivative (7b) and cyclobutaquinazoline (8b). On the other hand,
      UV-irradiation of 1c led to the bond shift isomer (5c) whose photolysis in the
      presence of TFA gave rise to the formation of the
      [6.4.0.0(1,3).0(2,6).0(4,8)]dodecane isomer (3c).

PMID- 11594051
TI  - Isomerization of DNA-bound distilbazolium ligand induced by electron transfer
      from photoexcited tris(1,10-phenanthroline)Ru(II).
AB  - The ability of the DNA duplex to behave as an efficient organized medium for cis
      trans isomerization induced by electron transfer (ET) has been explored.
      Isomerization studies, luminescence quenching and DNA photocleavage assays show
      that photoexcited Ru(1,10-phenanthroline [phen])3(2+) transfers an electron to
      E,Z1,4-bis[2-(1-methylpyridinium-4-yl)vinyl]benzene (E,Z pMPVB), which
      subsequently undergoes one-way isomerization to E,E pMPVB. The unusual feature of
      the system is manifested by the lack of friction that is usually imposed on the
      photoisomerizable ligand by highly organized media. The apparent rate of ET in
      DNA increases when compared with the homogeneous solution. However, after
      correction for the local concentration of the reagents onto the biopolymer, the
      rate constant becomes independent of the DNA concentration and is at least 4 x
      10(2) times smaller than that in the homogeneous aqueous solution. Using the
      photoinduced isomerization system, a large enhancement in the efficiency of
      single-strand break formation was found in plasmid DNA over that for
      Ru(phen)3(+2) alone using irradiation at lambda > 480 nm.

PMID- 11594053
TI  - Sunlight induces N epsilon-(carboxymethyl)lysine formation from glycated
      polylysine-iron(III) complex.
AB  - Sunlight was found to strongly induce the formation of N epsilon
      (carboxymethyl)lysine (CML) from glycated polylysine in the presence of Fe(III)
      ion. The initial step of this Fe(III)-catalyzed CML formation was noted to be
      similar to that of blueprint photography as was confirmed by the production of
      Turnbull's blue in sunlight-exposed glycated human serum albumin ferricyanide
      solution in the presence of Fe(III). Based on this, photoinduced oxidative C-C
      bond cleavage of the Amadori compound was assumed to be initiated by
      photochemical single electron transfer front ligand to Fe(III) in the Fe(III)
      Amadori compound complex affording the Fe(II)-Amadori compound radical
      intermediate, which eventually yields either CML or active oxygen species. CML is
      thus a useful oxidative stress marker. The mechanism proposed here would explain
      the high accumulation of CML in lens protein and skin actinic elastosis.

PMID- 11594052
TI  - Photostabilization of butyl methoxydibenzoylmethane (Avobenzone) and ethylhexyl
      methoxycinnamate by bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S),
      a new UV broadband filter.
AB  - It is now well documented that chronic UVA exposure induces damage to human skin.
      Therefore, modern sunscreens should not only provide protection from both UVB and
      UVA radiation but also maintain this protection during the entire period of
      exposure to the sun. UVA filters, however, are rare and not sufficiently
      photostable. We investigated the effect of the introduction of a new UV filter,
      bis-ethylhexyloxyphenol methoxyphenyl triazine (Tinosorb S), in oil in water
      sunscreen formulations on the photostability of butyl methoxydibenzoylmethane
      (Avobenzone [AVB]) after irradiation with an optically filtered Xenon arc source
      (UV irradiance adjusted at 1 mean effective dose [MED]/min). With
      spectrophotometrical methods to assess the sun protection factor (SPF) and UVA
      ratio and chromatographical methods to determine the amount of UV filters
      recovered after irradiation we showed that Tinosorb S prevented the
      photodegradation of AVB in a concentration-dependent way, leading to a sustained
      SPF and UVA ratio even after irradiation with doses of up to 30 MED. Since AVB
      was shown to destabilize ethylhexyl methoxycinnamate (EHM) we tested the effect
      of Tinosorb S in sunscreens containing this UV filter combination. Here too
      Tinosorb S showed photoprotective properties toward both UV filters. Thus,
      Tinosorb S can be used successfully to improve the photostability and efficiency
      of sunscreens containing AVB and EHM.

PMID- 11594054
TI  - Effect of cloud on UVA and exposure to humans.
AB  - The daily autumn and winter ultraviolet-A (320-400 nm) (UVA) exposures and 6 min
      UVA irradiance data for a southern hemisphere subtropical site (Toowoomba,
      Australia, 27.6 degrees S, 151.9 degrees E) are presented. This data is used to
      quantify the effect of cloud on UVA using an integrated sky camera and radiation
      system. Additionally, an estimate of the effect of enhanced UVA exposure on
      humans is made. The measurement system consisted of broad-band visible-infrared
      and UVA sensors together with a sun tracking, wide-angle video camera. The mean
      daily June exposure was found to be 409 kJ m-2. Under the constraints of the
      uncertainty of both the UVA measurement system and clear-sky model, one case of
      enhanced UVA irradiance was found. Three cases of cloud enhancement of daily UVA
      exposure, approaching clear-sky levels, were also determined using a calculated
      clear-sky envelope. It was also determined that for a fulltime outdoor worker the
      additional UVA exposure could approach approximately that of one third of a full
      winter's day. For indoor workers with an outside lunch break of 12:00-1:00 P.M.
      the additional UVA exposure was on an average 6.9 kJ m-2 over three cloud
      enhanced days. To the authors' knowledge this is the first paper to present some
      evidence of cloud-enhanced UVA human exposure.

PMID- 11594055
TI  - Evaluation of sunscreen protection in human melanocytes exposed to UVA or UVB
      irradiation using the alkaline comet assay.
AB  - The in vivo assessment of sunscreen protection does not include the
      photogenotoxicity of UVA or UVB solar radiation. Using the comet assay we have
      developed a simple and rapid technique to quantify sunscreen efficacy against DNA
      damage induced by UV light. Cutaneous human melanocytes from primary cultures
      were embedded in low-melting point (LPM) agarose and exposed to UVA (0.8 J/cm2)
      or to UVB (0.06 J/cm2) through a quartz slide covered with 10 microL volumes of
      sunscreens. DNA single-strand breaks induced directly by UVA at 4 degrees C and
      indirectly through nucleotide excision repair by UVB following a 35 min
      incubation period at 37 degrees C were quantified using the comet assay. Tail
      moments (TM) (tail length x %tail DNA) of 100 cells/sample were determined by
      image analysis. DNA damage was evaluated with a nonlinear regression analysis on
      the normalized distribution frequencies of TM using a chi 2 function. The
      coefficients of genomic protection (CGP) were defined as the percentage of
      inhibition of DNA lesions caused by the sunscreens. Twenty-one sunscreens were
      evaluated, and the calculated CGP were compared with the in vivo sun protective
      factor (SPF) and with the protection factor UVA (PFA). Nonlinear relationships
      were found between SPF and CGPUVB and between PFA and CGPUVA.

PMID- 11594056
TI  - Melanin offers protection against induction of cyclobutane pyrimidine dimers and
      6-4 photoproducts by UVB in cultured human melanocytes.
AB  - The goal of this investigation was to correlate the melanin content in human
      pigmentary cells with the generation of UVB-induced photoproducts and to examine
      the relationship between the melanin content and the removal of the
      photoproducts. Cultured melanocytes from light-skinned individuals synthesized
      less melanin and produced more cyclobutane pyrimidine dimers and 6-4
      photoproducts upon UVB exposure than did melanocytes from black skin. Tyrosine
      stimulated melanogenesis provided protection against DNA damage in both cell
      types. In another set of pigmented cell lines a ratio between eumelanin and
      pheomelanin was determined. The assessment of association between DNA damage
      induction and the quantity and quality of melanin revealed that eumelanin
      concentration correlated better with DNA protection than pheomelanin. Skin type-I
      and skin type-VI melanocytes, congenital nevus (CN)-derived cells and skin type
      II melanocytes from a multiple-melanoma patient were grown in media with low or
      high L-tyrosine concentration. The cells were irradiated with 200 J/m2 UVB, and
      the levels of the photoproducts were determined immediately and after 6 and 24 h.
      Once again the induction of the photoproducts was mitigated by increased
      melanogenesis, and it was inversely correlated with the skin type. No significant
      differences were found for the removal of photoproducts in the cultures of skin
      types I and VI and CN cells. No indications of a delay in the removal of
      photoproducts in the melanocytes from the multiple-melanoma patient were found
      either.

PMID- 11594057
TI  - CP43', the isiA gene product, functions as an excitation energy dissipator in the
      cyanobacterium Synechococcus sp. PCC 7942.
AB  - Under conditions of iron deficiency certain cyanobacteria induce a chlorophyll
      (Chl)-binding protein, CP43', which is encoded by the isiA gene. We have
      previously suggested that CP43' functions as a nonradiative dissipator of light
      energy. To further substantiate its functional role an isiA overexpression
      construct was introduced into the genome of a cyanobacterium Synechococcus sp.
      PCC 7942 (giving isiAoe cells). The presence of functional CP43' in isiAoe cells
      was confirmed by Western blot as well as by the presence of a characteristic
      blueshift of the red Chl a absorption peak and a notable increase in the 77 K
      fluorescence peak at 685 nm. Compared to wild-type cells isiAoe cells, with
      induced CP43', had both smaller functional antenna size and decreased yields of
      room temperature Chl fluorescence at various light irradiances. These
      observations strongly suggest that isiAoe cells, with induced CP43', have an
      increased capacity for dissipating light energy as heat. In agreement with this
      hypothesis isiAoe cells were also more resistant to photoinhibition of
      photosynthesis than wild-type cells. Based on these results we have further
      strengthened the hypothesis that CP43' functions as a nonradiative dissipator of
      light energy, thus protecting photosystem II from excessive excitation under iron
      deficient conditions.

PMID- 11594058
TI  - Nonphotosynthetic reduction of the intersystem electron transport chain of
      chloroplasts following heat stress. The pool size of stromal reductants.
AB  - The properties of a negative transient signal (negative peak) observed during the
      first seconds of the induction of the photoacoustic (PA) signal in dark-adapted
      barley leaves treated with methyl viologen (MV) and diuron and then exposed to
      high temperatures have been examined. Under those conditions no electron donation
      from photosystem II (PSII) occurred, and electron flow through PSI could be
      supported only by soluble reductants located in the chloroplast stroma. The
      negative peak was observed only if the PA signal had been monitored at low, and
      not high, frequencies. The peak obviously originated from the oxygen consumption
      by PSI. The size of the peak increased as the temperature of preheating was
      raised from 39 to 45 degrees C. The size of the peak decreased exponentially with
      a half-time of 3.7 s during illumination under low light. This decrease was found
      to be much faster under strong light. The recovery of the peak during dark
      acclimation required several minutes. It is concluded that the negative peak
      reflects the oxygen consumption supported by stromal reductants, their pool being
      rapidly exhausted under light in the presence of MV. The maximal size of the pool
      was calculated as 140 eq: P700 in dark-adapated leaves.

PMID- 11594059
TI  - Time-dependent changes in the carotenoid composition and preferential binding of
      spirilloxanthin to the reaction center and anhydrorhodovibrin to the LH1 antenna
      complex in Rhodobium marinum.
AB  - Carotenoids were isolated from the cells of Rhodobium marinum, and their
      structures were determined by mass spectrometry and 1H nuclear magnetic resonance
      spectroscopy; the carotenoids include lycopene, rhodopin, anhydrorhodovibrin,
      rhodovibrin and spirilloxanthin. Time-dependent changes in the carotenoid
      composition in the reaction center (RC) and the light-harvesting complex 1 (LH1)
      were traced by high-performance liquid chromatography analysis of the extracts.
      The carotenoid composition changed according to the spirilloxanthin biosynthetic
      pathway. However, spirilloxanthin having the longest conjugated chain was always
      preferentially bound to the RC, and anhydrorhodovibrin and other precursors to
      the LH1.

PMID- 11594060
TI  - Comparison of photosensitizer (AIPcS2) quantification techniques: in situ
      fluorescence microsampling versus tissue chemical extraction.
AB  - A noninvasive in situ fluorescence-based method for the quantification of the
      photosensitizer chloroaluminum disulfonated phthalocyanine was compared to the
      highly accurate but nonreal time ex vivo spectrofluorometry method. Our in vivo
      fluorescence technique is designed to allow real-time assessment of
      photosensitizer in tumor and normal tissues and therefore temporally optimal
      light delivery. Laser-induced fluorescence was used to measure photosensitizer
      concentration from multiple microscopic regions of tissue. Ex vivo chemical
      extraction was used to quantify photosensitizer concentration in the same volume
      of tissue. The amount of photosensitizer in the vascular and/or parenchymal
      compartments of skeletal muscle and liver was determined by quantifying
      fluorescent signal in vivo, ex vivo and after blood removal. Confocal microscopy
      was used to spatially document photosensitizer localization 30 min and 24 h after
      delivery. While a linear correlation can exist between the fluorescence intensity
      measured by our fiber-optic bundle system and actual tissue concentration,
      temporal changes to this calibration line exist as the photosensitizer changes
      its partitioning fraction between the blood (vasculature) and the tissue
      parenchyma. In situ photosensitizer fluorescence microsampling (dosimetry)
      systems can be performed in real time and linearly correlated to actual tissue
      concentration with minimal intertissue variance. Tissue-specific differences may
      require temporal alterations in the calibration.

PMID- 11594061
TI  - Comparison of the effects of different antiviral treatments on the antioxidant
      systems of stroma-free hemoglobin.
AB  - The effect of virus inactivation by 1,9-dimethylmethylene blue (DMMB)
      phototreatment, methylene blue (MB) phototreatment or heat on the activities of
      antioxidant systems of stroma-free hemoglobin (SFH) was studied. DMMB
      photoinactivated human immunodeficiency virus by > 3.69 log10 under conditions
      that inactivated 3.33 log10 of vesicular stomatitis virus (VSV). Under conditions
      which inactivated VSV by 6.10 log10 (1.37 J/cm2 irradiation and 2 microM DMMB),
      there was little change in the methemoglobin (Met-Hb) formation, concentration of
      reduced glutathione (GSH), or superoxide dismutase (SOD), catalase (CAT) or
      glutathione peroxidase (GPX) activities. However, the activity of glutathione
      reductase (GR) was decreased by 77%. Under conditions that inactivated VSV by
      5.69 log10 (1.37 J/cm2 irradiation and 24 microM MB) there was little effect of
      MB phototreatment on SOD, CAT, GPX and GSH activities. However, GR activity was
      decreased by 74% and Met-Hb content reached 3.98%. Under conditions that
      inactivated VSV by more than 6.20 log10 (60 degrees C for 2 min), virucidal heat
      treatment resulted in 27% Met-Hb formation and decreased GPX activity by 43%. No
      significant decline in SOD, CAT or GR activities or GSH concentration was
      observed. These results suggest that, compared with heat treatment and MB
      phototreatment, virucidal DMMB treatment preserves not only the oxidative state
      of hemoglobin but also the antioxidant systems against superoxide and hydrogen
      peroxide, although the reduced GR activity may limit the quenching capacity of
      antioxidants in DMMB-treated SFH.

PMID- 11594062
TI  - Isoflavonoid compounds from red clover (Trifolium pratense) protect from
      inflammation and immune suppression induced by UV radiation.
AB  - Isoflavones derived from many edible plants have been reported to possess
      significant antioxidant, estrogenic and tyrosine kinase inhibitory activity.
      Genistein has been found previously to provide protection from oxidative damage
      induced by UV radiation both in vitro and following dietary administration. We
      have therefore examined the potential of a number of isoflavones from red clover
      (Trifolium pratense) and some metabolically related compounds to offer protection
      from UV irradiation in hairless mice by topical application after UV exposure. We
      show that whereas the primary isoflavones, daidzein, biochanin A and
      formononetin, were inactive, 20 microM lotions of genistein and the metabolites
      equol, isoequol and the related derivative dehydroequol had powerful potential to
      reduce the inflammatory edema reaction and the suppression of contact
      hypersensitivity induced by moderate doses of solar-simulated UV radiation. For
      equol the protection was concentration dependent and 5 microM equol markedly
      reduced the UV-induced inflammation but abrogated the UV-induced
      immunosuppression. Equol protected similarly from immunosuppression induced by
      the putative epidermal mediator, cis-urocanic acid (UCA), indicating a potential
      mechanism of action involving inactivation of this UV-photoproduct. Since
      immunosuppression induced by both UV radiation and by cis-UCA appears to be an
      oxidant-dependent response our observations support the actions of these
      topically applied isoflavones and their metabolites as antioxidants. They also
      indicate that lotions containing equol, unlike topical UV sunscreens, more
      readily protect the immune system from photosuppression than from the
      inflammation of the sunburn reaction, even when applied after exposure, and thus
      such compounds may have a future role as sun-protective cosmetic ingredients.

PMID- 11594063
TI  - Suppression of UVB-induced cutaneous erythema by a previous UVB exposure.
AB  - People who vacation in sunny places are exposed to the sun on multiple occasions
      at least on a daily basis. The clinical assessment of sun exposure is erythema in
      the first 48 h after exposure and pigmentation at times greater than 3-5 days.
      The purpose of this investigations was to determine the extent to which
      consecutive erythemogenic exposures result in additive erythema responses.
      Studies were conducted in which volunteers were first exposed to a graded series
      of fluences of UVB radiation and then on subsequent days (1-3 days) the same
      sites along with the surrounding unexposed skin were challenged with varying
      fluences of UVB radiation. The erythema reactions were assessed clinically and
      were objectively documented with diffuse reflectance spectroscopy. The sites that
      received two exposures always showed a reduced erythema response compared to a
      single erythemogenic exposure. The suppression of erythema was more pronounced
      when the second exposure was given 48 h after the first. The erythema suppression
      was maximal when the first exposure was at 1.3 minimum erythema dose (MED). The
      pigment response to the first exposure was completely suppressed for fluences
      less than 1.5 MED. We thus provide evidence for a decoupling of the classical
      sequence of erythema-pigmentation response. We also show that the erythema
      induced by a second exposure may be substantially suppressed by an earlier
      exposure, and that this cannot be due to melanin photoprotection or due to
      substantial thickening of the stratum corneum. We propose that the cause may be
      some diffusible element of yet unknown origin.

PMID- 11594064
TI  - Correlation between the loss of the chaperone-like activity and the oxidation,
      isomerization and racemization of gamma-irradiated alpha-crystallin.
AB  - Alpha-crystallin possesses a molecular chaperone-like activity that prevents
      proteins from aggregating; however, the mechanism of this activity is not well
      known. Here we have taken gamma-irradiated alpha-crystallin and studied the
      relationship between the decrease in chaperone-like activity and the
      modifications such as oxidation, isomerization and racemization of amino acids in
      this molecule. We found that the chaperone-like activity of alpha-crystallin
      decreased with increasing gamma irradiation. After 4000 Gy gamma irradiation the
      activity of alpha-crystallin was reduced to 40% of the level of nonirradiated,
      native alpha-crystallin. The circular dichroism spectrum showed that the
      secondary structure of the irradiated alpha-crystallin had not changed. However,
      its tertiary structure appeared to change following more than 1000 Gy
      irradiation. Sodium dodecyl sulfatepolyacrylamide gel electrophoresis also
      indicated that cross-linking of alpha-crystallin increased with increasing
      radiation doses. Irradiated and nonirradiated alpha-crystallin was subjected to
      trypsin digestion and peptide analysis by reverse-phase high-performance liquid
      chromatography and mass and sequence analysis. Depending on the radiation dose,
      Met-1 of alpha A-crystallin was oxidized to methionine sulfoxide. In addition,
      Asp-151 of alpha A-crystallin was isomerized to the beta-Asp form after
      irradiation, and racemization of Asp-151 decreased. Thus, the loss of the
      chaperone-like activity of alpha-crystallin is related to changes in its
      isomerization, oxidation and racemization.

PMID- 11594065
TI  - Environmental effects on the photochemistry of A2-E, a component of human retinal
      lipofuscin.
AB  - Several retinal dystrophies are associated with the accumulation of lipofuscin, a
      pigment mixture, in the retinal pigment epithelium (RPE). One of the major
      fluorophores of this mixture has been identified as the bis-retinoid pyridinium
      compound, A2-E. Because this compound absorbs incident radiation that is
      transmitted by the anterior segment of the human eye, photophysical and
      photochemical studies were performed to determine if A2-E could photosensitize
      potentially damaging reactions. Steady-state fluorescence measurements indicate
      that the fluorescence emission maximum and quantum yield are very sensitive to
      the chemical environment and a correlation between these two parameters and the
      solvent dielectric constant is observed. Time-resolved absorption experiments of
      A2-E in pure organic solvents showed no formation of transient species on the
      timescale of our experiments. However, when these measurements were repeated for
      A2-E in Triton X-100 micelles, a short-lived (tau approximately 14 microseconds),
      weak absorption was observed. This species is quenched by oxygen (k = 2 x 10(9) M
      1 s-1) and by the addition of the antioxidants, cysteine and N,N,N',N'
      tetramethylphenylenediamine. Quenching of this species by 2,3,5
      trimethylhydroquinone results in the formation of the 2,3,5-trimethylsemiquinone
      free radical and an increase in yield of the A2-E-derived species. Sensitization
      of the A2-E triplet excited state indicates that the species observed in micelles
      upon direct excitation is not consistent with the triplet excited state. Based on
      these data we tentatively assign this absorption to a free radical. In the RPE
      these initial processes can ultimately lead to damage to the tissue through the
      formation of peroxides and other oxidized species.

PMID- 11594066
TI  - Pharaonis phoborhodopsin binds to its cognate truncated transducer even in the
      presence of a detergent with a 1:1 stoichiometry.
AB  - Pharaonis phoborhodopsin (ppR) (also pharaonis sensory rhodopsin II) is a
      receptor of the negative phototaxis of Natronobacterium pharaonis. ppR forms a
      complex with its pharaonis halobacterial transducer (pHtrII), and this complex
      transmits the light signal to the sensory system in the cytoplasm. The expressed
      C-terminal-His tagged ppR and C-terminal-His tagged truncated pHtrII (t-Htr) in
      Escherichia coli (His means the 6x histidine tag) form a complex even in the
      presence of 0.1% of n-dodecyl-beta-D-maltoside, and the M-decay of the complex
      became about twice slower than that of ppR alone. The photocycling rates under
      varying concentration ratios of ppR to t-Htr in the presence of detergent were
      measured. The data were analyzed on the following assumptions: (1) the M-decay of
      both ppR alone and the complex followed a single exponential decay with different
      time constants; and (2) the M-decay under varying concentration ratios of ppR to
      t-Htr, therefore, followed a biexponential decay function which combined the
      decay of the free ppR and that of the complex as photoreactive species. From
      these analyses we estimated the dissociation constant (15.2 +/- 1.8 microM) and
      the number of binding sites (1.2 +/- 0.08).

PMID- 11594067
TI  - Thermodynamics of the early steps in the photocycle of Natronobacterium pharaonis
      halorhodopsin. Influence of medium and of anion substitution.
AB  - The enthalpy (delta H) and structural volume changes (delta V) associated with
      the formation and decay of the early intermediate K600 in the photocycle of
      Natronobacterium pharaonis halorhodopsin (pHR), an inward-directed anion pump,
      were obtained by laser-induced optoacoustic spectroscopy. A large expansion is
      associated with K600 formation, its value depending on the medium and on the
      anion (Cl-, NO3-, Br-, I-). A smaller expansion is associated with K600 decay to
      L520. A contraction is found for the same step in the case of the azide-loaded
      pHR which is an efficient outward-directed proton pump. Thus, the conformational
      changes in L520 determine the direction and sign of charge translocation. The
      linear correlation between delta H and delta V for chloride-loaded pHR observed
      upon mild medium variations is attributed to enthalpy-entropy compensation
      effects and allows the calculation of the free-energy changes, delta GK = (97 +/-
      16) kJ/mol and delta GKL = -(2 +/- 2) kJ/mol. Different from other systems, delta
      S correlates negatively with delta V in the first steps of the pHR photocycle.
      Thus, the space around the anion becomes larger and more rigid during each of
      these two steps. The photocycle quantum yield was 0.52 for chloride-pHR as
      measured by laser flash photolysis.

PMID- 11594068
TI  - Medication restrictions: feeling the side effects.

PMID- 11594069
TI  - The challenge of putting a face on addiction.

PMID- 11594070
TI  - Outcomes: why isn't everyone doing this?

PMID- 11594071
TI  - Feedback: a key to improving therapy outcomes.

PMID- 11594072
TI  - Stop whining, and get thee to BHT!

PMID- 11594073
TI  - Connecting the dots: moving to evidence-based practice.

PMID- 11594074
TI  - Technology & communication issues for the next decade.

PMID- 11594075
TI  - Searching for gold in the river of technology. A review of strategic technology
      planning.

PMID- 11594076
TI  - Failing to manage--managing to fail. A search for clinical scheduling solutions.

PMID- 11594077
TI  - Could online substance abuse counseling take hold?

PMID- 11594078
TI  - Making the best of a disturbed mind.

PMID- 11594080
TI  - Leaders in American medicine. David M. Kipnis, M.D.

PMID- 11594079
TI  - The physician who ran for president: the life of Leonard Wood--a study in
      professionalism.

PMID- 11594081
TI  - The ABCs of effective teaching.

PMID- 11594082
TI  - The art of observation.

PMID- 11594083
TI  - Miranda health care rights.

PMID- 11594084
TI  - Creativity and illness: Christopher Smart and Samuel Johnson.

PMID- 11594085
TI  - "Decision making for severely brain-injured newborns".

PMID- 11594086
TI  - "Decision making for severely brain-injured newborns".

PMID- 11594087
TI  - Thomas Mann's the Transposed Heads: an accidental allogenic transplantation with
      unfavorable outcome.

PMID- 11594088
TI  - 1999 National Hospital Discharge Survey: annual summary with detailed diagnosis
      and procedure data.
AB  - OBJECTIVES: This report presents 1999 national estimates and selected trend data
      on the use of non-Federal short-stay hospitals in the United States. Estimates
      are provided by demographic characteristics of patients discharged, geographic
      region, ownership, and bed size of hospitals, principal expected source of
      payment, conditions diagnosed, and surgical and nonsurgical procedures performed.
      Measurements of hospital use include number and rate of discharges and days of
      care, and the average length of stay. Estimates of first-listed diagnoses, days
      of care, all-listed diagnoses, and all-listed procedures are presented according
      to their code number in the International Classification of Diseases, 9th
      Revision, Clinical Modification (ICD-9-CM). METHODS: The estimates are based on
      data collected through the National Hospital Discharge Survey. The survey has
      been conducted annually by the National Center for Health Statistics since 1965.
      In 1999 data were collected for approximately 300,000 discharges. Of the 487
      eligible non-Federal short-stay hospitals in the sample, 458 (94 percent)
      responded to the survey. RESULTS: An estimated 32.1 million inpatients were
      discharged from non-Federal short-stay hospitals in 1999. These patients used an
      estimated 160.1 million days of care. Patients 65 years of age and over accounted
      for 40 percent of discharges and used 48 percent of days of care. More than half
      of all patients under age 65 in 1999 had a principal expected source of payment
      from a private source. Patients discharged from nonprofit hospitals accounted for
      nearly 78 percent of all discharges. Heart disease accounted for 4.5 million
      discharges, and deliveries made up 3.8 million discharges. An estimated 3.7
      million newborn infants were discharged from short-stay hospitals after average
      stays of 3.2 days.

PMID- 11594089
TI  - Elevated homocysteine with weight loss.

PMID- 11594090
TI  - Overlooked problems in morbidly obese patients.

PMID- 11594091
TI  - Metabolic syndrome in severely obese patients.
AB  - BACKGROUND: The authors assessed the prevalence of diabetes, hypertension,
      dyslipidemia and metabolic syndrome in patients with a high degree of obesity.
      METHODS: A retrospective investigation was planned in a cohort of obese patients
      with a wide range of body mass index (BMI) referred to a large University
      Hospital for weight loss. RESULTS: An increase in prevalence of diabetes and
      hypertension with increase in the degree of obesity was observed, while the
      prevalence of dyslipidemia and metabolic syndrome appeared to be independent of
      the BMI values. CONCLUSION: In severely obese patients a still unknown factor
      which affects differently glucose and lipid metabolism cannot be excluded.

PMID- 11594092
TI  - Impartial long-term review of vertical banded gastroplasty in a low volume
      community hospital practice.
AB  - BACKGROUND: There is some concern whether bariatric surgery can be done well at
      low volumes or in a community hospital setting. This paper reports an impartial
      assessment of 25 vertical banded gastroplasties (VBG) over 13 years in a 228-bed
      non-teaching community hospital. METHODS: Charts were reviewed and patients
      interviewed by an independent investigator. Complications, weight loss,
      satisfaction and quality of life were assessed. RESULTS: There were no
      fatalities, no splenic tears, no stomal stenosis and no symptomatic
      gastroesophageal reflux. Two reoperations and five incisional hernias were noted.
      Hypertension was eliminated in 57% and dyspnea in 55%. BMI fell from 44.3 to 34.9
      kg/m2 after 6.2 years. BMI decreased more than 10 kg/m2 (10-30) for 15 patients
      and less than 10 kg/m2 for 10 patients (4-10 for 7, 0 for 1 and a gain for 2).
      56% of patients were fully satisfied with the results. Quality of life indicated
      excellent physical function, physical role and lack of body pain, good general
      health, social function, emotional role and mental health, but lower vitality.
      100% felt better than a year ago. CONCLUSION: Results from a low-volume community
      hospital general surgical practice are similar to those from specialized series.
      Obesity is so common, its non-surgical treatment so ineffective and the VBG so
      well established, that excluding this intervention from community hospitals is
      untenable.

PMID- 11594093
TI  - Bariatric surgery in the community hospital.

PMID- 11594094
TI  - Left ventricular function and cardiopulmonary performance following surgical
      treatment of morbid obesity.
AB  - BACKGROUND: It is well established that morbid obesity affects the respiratory
      system and the diastolic function of the heart. During exercise, cardiopulmonary
      reserve is exhausted because of augmented requirements, leading to a significant
      intolerance. A study was undertaken to investigate the influence of body weight
      loss on the characteristics of the left ventricle (LV) and on exercise capacity
      in obese patients before and 6 months, following vertical banded gastroplasty
      (VBG). METHODS: 16 morbidly obese individuals (BMI > 40 kg/m2) scheduled for VBG
      were studied. A symptom-limited cardiopulmonary exercise test and a complete
      transthoracic echocardiogram were performed 1 day before operation and 6 months
      postoperatively (after the patients achieved a body weight loss of > 20% of their
      pre-operative values). RESULTS: Exercise duration increased significantly 6
      months following surgery. The mean O2 consumption at peak exercise (peak VO2) and
      at the anaerobic threshold (VO2AT) was significantly higher after weight loss. 6
      months after VBG the LV thickness decreased significantly. Regarding the
      diastolic indices, isovolumic relaxation time (IVRT) and early/late (E/A)
      velocity ratio, there was a significant improvement after weight loss. Simple
      linear regression analysis revealed that peak VO2 and VO2AT were significantly
      correlated with IVRT and E/A velocity ratio. CONCLUSIONS: Weight loss after VBG
      improves the cardiac diastolic function and this is associated with an
      improvement in cardiopulmonary exercise performance. Left ventricular filling
      variables could be considered among the most important determinants of exercise
      intolerance in obese individuals.

PMID- 11594095
TI  - Starting a successful bariatric surgical practice in the community hospital
      setting.
AB  - BACKGROUND: 3% of the population is morbidly obese and experience many associated
      medical problems. Surgical procedures have been shown to achieve sustained weight
      loss not attainable by other measures, lessening the co-morbidities. However,
      most general surgeons have been reluctant to expand their practice to include
      bariatric surgery. The current study demonstrates the benefits of including
      bariatric surgery in a general surgeon's practice in a community hospital.
      METHODS: Hospital charts of patients undergoing a gastric bypass procedure
      between 1997 and 2000 were reviewed. Demographic data, co-morbid conditions,
      intra-operative times, and post-operative weight loss were recorded. Follow-up
      data was obtained using a mailed survey based on the BAROS survey. RESULTS: 168
      patients underwent a Roux-en-Y gastric bypass procedure. Follow-up was obtained
      for 86 patients. Average pre-operative weight was 141 kg (BMI = 50). There was an
      average loss of 55% of excess weight by the second post-operative year. Operative
      times decreased as the number of the procedures performed by the surgeon
      increased. Over half of the patients surveyed reported improvements for each of
      the co-morbid conditions that were assessed (i.e., diabetes, back pain, etc.).
      Five categories of quality of life were assessed, and over 66% of patients
      reported improvements in all areas. In 44% of the patients, payment was obtained
      from private insurance and 56% from Medicare or Medicaid. There were no deaths.
      CONCLUSION: Adding bariatric surgery to a general surgeon's practice in the
      community setting can be beneficial to patients, intellectually stimulating and
      emotionally rewarding for the surgeon, and economically feasible for the
      institution.

PMID- 11594096
TI  - Combined laparoscopic/endoscopic anvil placement for the performance of the
      gastroenterostomy.
AB  - BACKGROUND: We developed the laparoscopic gastric bypass in 1993 and first
      reported the technique and results in 1994. The technique for the
      gastroenterostomy was derived from the method used in the percutaneous endoscopic
      gastrostomy tube placement. Some have questioned the safety of this technique,
      and alternatives have been proposed. METHOD: Prospectively, we have followed and
      recorded the results of our laparoscopic patients. To date we have performed over
      1,400 laparoscopic gastric bypass operations using the same technique of anvil
      placement: pulling the anvil down from the mouth to the stomach pouch with a
      percutaneously placed wire. All patients underwent upper GI endoscopy following
      the anvil placement, and a water-soluble upper GI series was obtained on the
      first postoperative day. RESULTS: There have been no esophageal injuries in the
      first 1400 patients on whom this technique was done. CONCLUSION: The percutaneous
      pull-wire technique is a safe and effective method to place the 21-mm circular
      stapler anvil for the performance of a laparoscopic gastroenterostomy.

PMID- 11594097
TI  - Evaluation of core temperature during laparoscopic and open gastric bypass.
AB  - BACKGROUND: Intraoperative hypothermia is a common event during open and
      laparoscopic abdominal surgery. The aim of this study was to compare changes in
      core temperature between laparoscopic and open gastric bypass (GBP). METHODS: 101
      patients with a body mass index (BMI) of 40-60 kg/m2 were randomly assigned to
      open (n = 50) or laparoscopic (n = 51) GBP. Anesthetic technique was similar for
      both groups. An external warming blanket and passive airway humidification were
      used intraoperatively. Core temperature was recorded at preanesthesia, at
      baseline (after induction) and at 30-min intervals; intra-abdominal temperature
      was additionally measured at 30-min intervals in a subset of 30 laparoscopic GBP
      patients. The number of patients who developed intraoperative and postoperative
      hypothermia (< 36 degrees C) was recorded. Length of operation for both groups
      and the amount of CO2 gas delivered during laparoscopic operations were also
      recorded. RESULTS: There was no significant difference between groups with
      respect to age, gender, mean BMI, and amount of intravenous fluid administered.
      After induction of anesthesia, core temperature significantly decreased in both
      groups; 36% of patients in the open group and 37% of patients in the laparoscopic
      group developed hypothermia. This percentage increased to 46% in the open group
      and 41% in the laparoscopic group during the operation, and then decreased to 6%
      in the open group and 8% in the laparoscopic group in the recovery-room. Core
      temperature increased during the operative procedure to reach 36.5 +/- 0.6
      degrees C in the open group and 36.3 +/- 0.5 degrees C in the laparoscopic group
      at 2.5 hours after surgical incision. Intra-abdominal temperature during
      laparoscopic GBP was significantly lower than core temperature at all measurement
      points (p < 0.05). Operative time was longer in the laparoscopic group than in
      the open group (232 +/- 43 vs 201 +/- 38 min, p < 0.01). Mean volume of gas
      delivered during laparoscopic GBP was 650 +/- 220 liters. CONCLUSION:
      Perioperative hypothermia was a common event during both laparoscopic and open
      GBP. Despite a longer operative time, laparoscopic GBP did not increase the rate
      of intraoperative hypothermia when efforts were made to minimize intraoperative
      heat loss.

PMID- 11594098
TI  - Eating behavior in morbidly obese patients undergoing gastric surgery:
      differences between obese people with and without psychiatric disorders.
AB  - BACKGROUND: This study analyzes eating behavior in a group of morbidly obese
      patients who have undergone gastric reduction surgery for weight loss, and
      evaluates whether the existence of psychiatric comorbidity marks significant
      differences in their eating behavior. METHODS: The study group was composed of
      100 morbidly obese patients (85 females, 15 males) who had received surgical
      treatment for weight reduction (vertical banded gastroplasty). 40 of these
      patients (40%) met ICD-10 criteria for the diagnosis of psychiatric disorders and
      were included in the "Psychiatric Obese group" (PO). The other 60 patients (60%)
      did not show ICD-10 diagnostic criteria and were included in the "Non-Psychiatric
      Obese group" (NO). Each patients completed the Binge Eating Scale (BES), the
      Three Factor Eating Questionnaire, the Bulimia Investigatory Test-Edinburgh
      (BITE), and the Eating Disorder Inventory (EDI). RESULTS: Significant differences
      were found between the two groups (PO and NO) in the Binge Eating Scale (p <
      0.001), Three Factor Eating Questionnaire subscale Disinhibition (p < 0.001),
      BITE (p < 0.001), Eating Disorder Inventory subscale Perfectionism (p < 0.002),
      and Global EDI (p < 0.001). Logistic regression analysis showed correlation
      between PO group and Global EDI (Odds Ratio OR = 1.43) and BITE (OR = 1.16). No
      significant gender differences were found for eating behavior, clinical
      diagnosis, age, percentage of weight loss, time after operation, and BMI before
      surgery. CONCLUSION: Surgically treated morbidly obese patients with a
      psychiatric disorder (PO) have a more destructured eating pattern (with a
      predominance of binge eating and disinhibition) than NO.

PMID- 11594099
TI  - The psychology of gastric bypass surgery.
AB  - BACKGROUND: This article discusses the importance of psychological evaluation of
      gastric bypass (GBP) surgery candidates and post-surgical psychological support
      services, using the Center for Weight Reduction Surgery at Montefiore Medical
      Center as a model. The study of psychological predictors of post-operative
      outcome is in its beginning stages, and the small body of literature on this
      topic is reviewed. METHODS: 115 GBP surgery candidates completed a clinical
      interview and a self-report measure, the MMPI-2. RESULTS AND CONCLUSIONS: A high
      prevalence of psychopathology and personality disturbance was found in this
      population. The impact that psychological disturbance may have on post-operative
      outcome is discussed. The authors also provide a qualitative analysis of the
      psychological themes commonly found among this population, as well as
      psychosocial interventions that have been found helpful.

PMID- 11594100
TI  - Assessment of the effects of a taped cognitive behavior message on postoperative
      complications (therapeutic suggestions under anesthesia).
AB  - BACKGROUND: The authors studied whether playing a taped cognitive-behavior
      message during and immediately following bariatric surgery will improve
      performance of a postoperative regimen designed to enhance recovery. METHODS: The
      double-blinded placebo-controlled study consisted of 27 morbidly obese bariatric
      surgical patients randomly assigned to listen to either a blank (Controls) or a
      positive therapeutic message audiotape (Tape). A Postoperative Regimen Checklist
      (PRC) quantified different parts of the postoperative recovery regimen. RESULTS:
      The data showed that patients in the Tape group, compared to the Controls: 1)
      achieved better scores at most PRC assessment points (p < 0.05), 2) required less
      encouragement to perform tasks (p < 0.05), and 3) were discharged from the
      hospital a mean of 1.6 days earlier. CONCLUSIONS: A taped cognitive-behavioral
      message, played to patients repetitively during and immediately following
      bariatric surgery, is effective in enhancing postoperative compliance and
      reducing in-patient length of stay.

PMID- 11594101
TI  - Radiologic and endoscopic evaluation for laparoscopic adjustable gastric banding:
      preoperative and follow-up.
AB  - BACKGROUND: Laparoscopic adjustable silicone gastric banding (LASGB) has replaced
      vertical banded gastroplasty (VBG) as the most widespread restrictive bariatric
      operation in Europe. Although these two procedures are similar in principle, the
      experience concerning the preoperative examinations and follow-up cannot be
      arbitrarily transferred from VBG to LASGB. The reasons for and consequences drawn
      from radiologic and endoscopic examinations are described. METHODS: From December
      1996 to January 2000, 148 patients (84% women, average age 39 years, body weight
      127 kg, BMI 45 kg/m2) underwent LASGB. The mean follow-up was 17 months. Upper GI
      series, abdominal ultrasound, and gastroscopy were done before operation. The
      postoperative stoma adjustments were performed under radiological observation.
      All adjustments were analyzed. RESULTS: Preoperative: Of 147 upper GI series, 74
      showed hiatal hernia, 2 motility disorders, and 1 an incomplete malrotation. In
      104 gastroscopies, 35 reflux and 53 gastritis with 24 Helicobacter pylori
      infections were found. Postoperative: On average, 2.7 radiological adjustments
      were done per patient. Until satisfactory satiety and weight reduction, 78% of
      the patients needed 0-3 adjustments. Besides routine adjustments, an additional
      57 upper GI series were done in 35 patients, 44 times with opening of the stoma
      diameter. A total of 14 slippages and 4 pouch enlargements were found. A
      gastroscopy was required in 12 patients. CONCLUSION: Radiologic and endoscopic
      examinations before LASGB revealed pathology needing therapy in 42% of the
      patients and provided important additional information influencing the operative
      procedure. At an average follow-up of 17 months, 24% of the 148 patients needed
      unplanned additional upper GI series.

PMID- 11594102
TI  - Is a routine liquid contrast swallow following laparoscopic gastric banding
      mandatory?
AB  - BACKGROUND: The authors assess the value of liquid contrast medium swallow as a
      method to detect postoperative complications after laparoscopic adjustable
      gastric banding (LAGB) for the treatment of morbid obesity. METHODS: From January
      1996 to January 2001, 350 morbidity obese patients (295 women, 55 men) underwent
      a LAGB operation. All data were prospectively collected in a computerized
      databank. All patients underwent a jopomidol swallow (JS) study in the early
      postoperative phase to exclude perforation of the esophagus or stomach, which is
      one of the most serious complications occurring after the LAGB operation.
      Furthermore, the JS was performed to confirm band position and to exclude early
      pouch dilatation. RESULTS: Out of the 350 LAGB operations, 6(1.8%) early pouch
      dilatations and 4(1.2%) stomach perforations occurred. All early pouch
      dilatations were recognized on postoperative JS and immediately repaired
      laparoscopically. Of the perforations, one was recognized intraoperatively, and
      the other three were diagnosed postoperatively, either by contrast media
      extravasation on the JS (two patients) or by computer tomography. CONCLUSION:
      Presently, all patients undergo routine postoperative JS, which exposes them to
      radiation, causes patient discomfort, and entails additional costs of
      approximately 100 US$ per patient. Of the last 250 patients in our series, there
      have not been any cases of early pouch dilatation and since 1998 only one case of
      perforation has occurred, which could be easily suspected clinically. Therefore,
      we believe that in experienced centers, it is not necessary to perform routine
      postoperative contrast media studies and recommend JS only in cases of
      complicated postoperative courses.

PMID- 11594103
TI  - Causes of dissatisfaction in some patients after adjustable gastric banding.
AB  - BACKGROUND: The laparoscopic application of the adjustable gastric band has
      gained widespread acceptance as a gastric restrictive procedure. The weight loss
      been well documented. This paper evaluates the patients' satisfaction. METHODS:
      Between April 1995 and July 1999, 82 consecutive patients underwent the Lap-Band
      procedure. RESULTS: Follow-up is 100%. The satisfaction index is high. 80% of all
      patients are extremely pleased or pleased. 15% of patients are displeased or
      extremely displeased. 5% have no opinion. The reason for low satisfaction differ,
      but 3 groups can be distinguished: 1) patients who suffered surgical
      complications; 2) patients who did not benefit from the procedure; 3) most
      importantly, patients who suffered psychological complications. CONCLUSION:
      Gastric Banding is a safe, standardized and effective operation, with good
      acceptance by the patients. More efforts have to be made to improve patient
      selection and to avoid surgical complications. Most importantly, more focus is
      needed on the psychological aspect of the procedure and its consequences.

PMID- 11594104
TI  - Leptin as an acute phase reactant after non-adjustable laparoscopic gastric
      banding.
AB  - BACKGROUND: Leptin is a hormone that regulates food intake; its concentrations
      are elevated in the majority of obese individuals. During inflammation, plasma
      leptin is usually increased and may contribute to the anorexia and cachexia of
      infection. The purpose of this study was to characterize the dynamics of
      circulating leptin in the early postoperative period in relation to the acute
      phase response in extremely obese patients undergoing laparoscopic non-adjustable
      gastric banding (LNAGB). We compared plasma leptin changes with 4 proinflammatory
      cytokines and BMI. METHODS: The prospective study was performed on 18 patients
      with 3rd degree obesity. Plasma concentration of leptin, tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL)-1, soluble IL-2 receptor (sIL-2R), and IL-6
      were estimated before operation and 24, 48, and 72 h after NALGB. RESULTS: We
      demonstrate statistically significant elevation of plasma leptin concentration
      (32.2 +/- 10.2 micrograms/l) 24 h after operation compared with preoperative
      status (18.4 +/- 5.2 micrograms/l, p < 0.05). There was diminished correlation of
      plasma leptin and BMI in this period. Leptin levels +48 and +72 h after banding
      quickly returned to preoperative levels. The regression coefficient was the
      highest for leptin and TNF-alpha 24 h after surgery (r = 0.40, p < 0.05), and for
      leptin and IL-6 24 h after surgery (r = 0.29, p < 0.05). There was no significant
      correlation between leptin and IL-1 and between leptin and sIL-2R respectively.
      CONCLUSIONS: During the non-infectious stress response (as with abdominal
      surgery), leptin shows itself as an acute phase reactant. Proinflammatory
      cytokines can be the main regulatory factors of leptin in this period.
      Significant correlation between leptin and TNF-alpha (similarly demonstrated by
      other authors in models of bacterial inflammation) indicates that TNF-alpha can
      be a crucial regulator of leptin generation in the early postoperative period.

PMID- 11594105
TI  - Patency of anastomoses after bilio-intestinal bypass: radioisotope demonstration.
AB  - BACKGROUND: Bilio-intestinal bypass (BIB) is effective for the treatment of
      refractory obesity. BIB permits bile flow into the non-functional jejunum,
      whereas food transit occurs via the remaining intestine. We used the radioisotope
      method of 99mTc-Hida cholescintigraphy (HC) in the follow-up of patients.
      METHODS: 21 patients were studied 3 months to 3 years after BIB with HC. After 3
      hours acquisition, images were reviewed by two independent observers. Regions of
      interest (ROIs) were drawn on images: liver parenchyma, cholecysto-jejunal
      anastomosis (CC), choledochus (COL). Radioactivity taken up by liver was compared
      with radioactivity of CC and COL. % radioactivity passing through CC (%CC) and
      through COL (%COL) were determined. The final parameter, -COL, indicates the
      radioactive bile which does not pass through the choledochus. RESULTS:
      Anastomoses were found patent a few months to 3 years after operation. -COL
      showed linear correlation with the decrease in cholesterolemia and in body weight
      in the 1st year after BIB. CONCLUSIONS: HC shows passage of radioactive bile
      through anastomoses and provides semiquantitative evaluation of bile flux
      diversion. Bile flux towards the gallbladder and non-functional jejunal limb far
      exceeds flux directed towards the duodenum via the choledochus.

PMID- 11594106
TI  - Laparoscopic biliopancreatic diversion for the treatment of morbid obesity:
      initial experience.
AB  - BACKGROUND: Open biliopancreatic diversion (BPD) is a proven effective operation
      for morbid obesity. We developed a technique which permits BPD to be performed
      laparoscopically. METHODS: 10 patients were submitted to BPD by laparoscopy in
      July and August 2000 for the treatment of morbid obesity. All patients were
      morbidly obese (BMI 40-55). RESULTS: All operations were performed by laparoscopy
      with no need to convert to laparotomy. No complications related to surgery were
      observed. CONCLUSION: The technique, with an acceptable level of complexity, can
      be safely executed by laparoscopy as described by Scopinaro.

PMID- 11594107
TI  - Volatile anesthesia in bariatric surgery.
AB  - BACKGROUND: Obesity causes anesthesiologists a broad variety of perioperative
      theoretical and practical problems. The aim of this study was to compare two
      protocols of anesthesia employing Isoflurane and Sevoflurane and evaluate the
      cardiorespiratory parameters, postoperative recovery and analgesia. METHODS: 90
      patients underwent biliopancreatic diversion. 60 patients (group A) received
      Isoflurane and 30 patients (group B) were anesthetized with Sevoflurane.
      Intraoperative monitoring consisted of EKG, invasive arterial pressure, SpO2,
      EtCO2, Etanest, Spirometry, urinary output and TOF. Cardiorespiratory parameters
      and end tidal expiratory concentrations of volatile agents were collected during
      specific phases of surgery: 1) before induction of anesthesia, 2) after
      intubation, 3) after skin incision, 4) after positioning of costal retractors, 5)
      in the reverse Trendelenburg position, 6) end of surgery. During the
      postoperative period the Aldrete test was carried out to evaluate the recovery
      from anesthesia. VAS was administered for 6 hours after the end of surgery to set
      the quality of analgesia. RESULTS: No statistically significant differences in
      cardiorespiratory parameters were found between the two groups. Extubation time
      was significantly less in the Sevoflurane Group than in the Isoflurane (15 +/- 7
      min vs 24 +/- 5 min, p < 0.05). The Sevoflurane Group showed an Aldrete score
      significantly higher than the Isoflurane (8.8 +/- 0.3 vs 8.1 +/- 0.4, p < 0.05).
      VAS values did not show statistical differences. CONCLUSION: The introduction of
      Sevoflurane, a volatile agent with rapid pharmacokinetic properties, seems to
      offer an interesting application in these patients.

PMID- 11594108
TI  - Heart block in patients after bariatric surgery accompanying sleep apnea.
AB  - BACKGROUND: Heart block and bradycardia during sleep has been reported in
      patients with obesity. The occurrence of bradyarrhythmias in patients after
      undergoing bariatric surgery has not been reported. METHODS: Over a period of 6
      months, 3 patients who underwent laparoscopic weight reduction surgery developed
      prolonged heart block during sleep. Clinical course and follow-up are presented.
      RESULTS: All 3 patients were diagnosed with sleep apnea. For 2 of these patients
      this was a new diagnosis. The episodes of heart block coincided with their
      episodes of sleep apnea. During follow-up of at least 6 months, no patient has
      had any adverse consequences related to their nocturnal heart block. CONCLUSION:
      Heart block during sleep is sometimes seen in patients undergoing bariatric
      surgery. The cause is sleep apnea, which often is worsened in the postoperative
      state due to narcotic analgesics. These patients require treatment of their sleep
      apnea, not pacemakers.

PMID- 11594109
TI  - Narcotic withdrawal syndrome following gastric bypass--a difficult diagnosis.
AB  - BACKGROUND: It is common for bariatric patients to experience postoperative
      nausea, depression and remorse for several months following surgery. Difficulty
      exists for the surgeon in delineating the physical from the psychological in
      treating these patients. Preoperative education, evaluation and preparation,
      although essential, will not identify nor eliminate all potential problems.
      METHODS: We report the case history of a patient who ultimately underwent
      reversal of her gastric bypass. Her symptoms required multiple procedures and
      hospital admissions for what appeared to be anatomical problems. All procedures
      were done laparoscopically. RESULTS: The patient's main complaints of persistent
      nausea and abdominal pain combined with radiographic evidence of sub-optimal
      anatomic construct led to multiple operative procedures. Psychological
      intervention relative to the persistent nausea and abdominal pain was
      ineffectual, although the supportive and consistent nature of the psychotherapy
      relationship was useful in overall patient stability and emotional well being.
      Complete reversal of the bypass did not effect improvement. Ultimately, the
      diagnosis of narcotic withdrawal prompted the institution of methadone treatment
      with complete cessation of the symptoms of nausea and pain. CONCLUSIONS: The
      diagnosis of narcotic withdrawal syndrome can be difficult in the postoperative
      bariatric patient. Psychological evaluation and support are essential elements of
      the program throughout the entire course of a patient's treatment experience.
      Laparoscopic techniques simplified the surgical care of this patient.

PMID- 11594110
TI  - Improvement of weight loss and metabolic effects of vertical banded gastroplasty
      by an added duodenal switch procedure.
AB  - BACKGROUND: Some patients who underwent vertical banded gastroplasty (VBG) need
      revisional operations because of poor weight loss and remaining comorbidities.
      The duodenal switch (DS) procedure with partial gastrectomy is known as an
      effective method for treatment of severe obesity and related dyslipoproteinemias
      and diabetes mellitus type 2 (DM2). Other investigations have shown that DS
      without gastric resection similarly corrects hypercholesterolemia and DM2 in the
      "less than" morbidly obese patients. METHODS: Based on this knowledge, we
      performed a DS simultaneously with hernioplasty and panniculectomy in a 63-year
      old woman with a fair EWL (36.4%), with remaining hypercholesterolemia and DM2 4
      years after VBG. The pouch stoma diameter was 13 mm, and there was no pouch
      dilation nor staple-line disruption. The previously partitioned stomach was left
      in place. H2-blockers and polyvitamins were prescribed after operation. RESULTS:
      1 year after DS there were no postoperative complications and undesirable effects
      except slight anemia. DS allowed improvement in weight loss, improved
      carbohydrate handling without need for insulin or other hypoglycemic agents, and
      corrected severe hypercholesterolemia. CONCLUSION: DS per se in the case
      presented had a decisive effect on DM2 and hypercholesterolemia. DS should be
      kept in mind as a second-step malabsorptive procedure after a failed purely
      restrictive operation.

PMID- 11594111
TI  - Liver transplantation in a case of steatohepatitis and subacute hepatic failure
      after biliopancreatic diversion for morbid obesity.
AB  - BACKGROUND: Biliopancreatic diversion (BPD) was designed to avoid the serious
      complications of jejunoileal bypass (steatohepatitis and hepatic failure).
      Although this is today considered a safe and effective procedure, a few reports
      of patients who developed steatohepatitis and subsequently died in hepatic
      failure exist. METHODS: We report a morbidity obese patient who developed
      subacute hepatitis resulting in hepatic failure 1 year after BPD. RESULTS:
      Because of irreversible liver failure the decision to perform a liver
      transplantation was made. The patient underwent emergency liver transplant and
      lengthening of the common limb. The course of liver transplantation and the
      patient's recovery were uneventful. CONCLUSION: Severe liver disease may rarely
      follow BPD. Liver transplantation and lengthening of the common bowel may be
      performed to treat these patients.

PMID- 11594112
TI  - Blind loop syndrome after biliopancreatic diversion: a diagnostic challenge.
AB  - BACKGROUND: Biliopancreatic diversion (BPD) according to Scopinaro's method is a
      safe and effective technique for treatment of morbid obesity. In this operation a
      side-to-side enteroenterostomy is created 60 cm proximal to the ileocecal valve.
      Malabsorption of fat and starch is one of the main goals of the BPD. Ingestion of
      an excess of fat leads to steatorrhea. As a side-effect, malabsorption of iron,
      calcium and other elements can occur causing anemia and hypocalcemia. The blind
      loop syndrome gives the same symptoms. METHODS: A lady was admitted with a long
      history of steatorrhea, anemia and hypocalcemia due to a blind loop syndrome
      after a BPD. The diagnostic problem in this patient is illustrated. RESULTS: The
      diagnosis was only made at exploratory laparotomy. CONCLUSION: The blind loop
      syndrome was then treated with resection of the blind loop and antibiotics.

PMID- 11594113
TI  - Small intestine gastric balloon impaction treated by laparoscopic surgery.
AB  - BACKGROUND: The BioEnterics intragastric balloon device (BIB) is being used as an
      adjunct for treatment of obesity. This procedure may have complications, mainly
      related to the migration of the balloon in the bowel, with abdominal cramping
      before anal extrusion. METHODS: We report a case of migration of a deflated BIB
      in the small bowel with obstruction. This device had been implanted 7 months
      earlier. RESULTS: The plain radiograph and the CT scan confirmed the diagnosis,
      and the patient was operated with opening of the bowel for removal of the device
      and the impacted food. The whole procedure was done via laparoscopy. The patient
      left the hospital on the 7th postoperative day. CONCLUSION: We report a small
      bowel obstruction by migration of a deflated BIB.

PMID- 11594114
TI  - Changes in lipid levels with percent of weight loss in morbid obesity.

PMID- 11594115
TI  - Unusual localization of visceral pain in peptic ulcer after biliopancreatic
      diversion.

PMID- 11594116
TI  - [Clinical aspects and etiology of erythroderma: an analysis of 64 cases].
AB  - The difficulty of exfoliative dermatitis lies in the finding of underlying
      causes. In the present study the profile of 64 patients with erythroderma
      diagnosed between 1.1.1990 and 31.12.1999 were analysed. Clinical, histological
      and laboratory findings and their relationship to the aetiology were
      investigated. A masculine:feminine ratio of 2.6:1 was found. Among these patients
      the most common causative factors were pre-existing dermatoses (58%) and drugs
      (16%). In about eleven percent of the patients exfoliative dermatitis was
      associated with malignancy. Six out of seven malignancies were found in males,
      five of them suffering from pre-existing dermatosis. In 16 percent of the
      patients no aetiology of erythroderma could be found. No laboratory or clinical
      findings were indicative for an underlying malignant condition. Since we
      demonstrated underlying neoplastic disorders in seven (11%) of the cases, five of
      them also suffering from pre-existing dermatosis, we consider it absolutely
      necessary to screen for such diseases in the presence of the diagnosis
      exfoliative dermatitis.

PMID- 11594117
TI  - [Pregnancy termination in Swiss hospitals. Results of a survey].
AB  - Based on the response of 84 hospitals and clinics to a questionnaire, an overview
      is given of the practice of pregnancy termination in a hospital setting in
      Switzerland. A comparison to current practice in the Netherlands rouses the
      question whether for 1st trimester abortions Swiss hospitals might use more often
      local anaesthesia, minimal dilatation, aspiration without subsequent curettage
      and patient surveillance of less than four hours as well as dilatation and
      evacuation (D&E) for 2nd trimester abortions.

PMID- 11594119
TI  - [Bone ultrasound and assessment of osteoporosis].

PMID- 11594118
TI  - [Pre- and postoperative transaminase changes within the scope of gastric banding
      in morbid obesity].
AB  - 20-30% of obese patients without concomitant liver disease show elevated liver
      tests (ALAT, ASAT, GGT) which are known to normalize after weight reduction.
      Little is known about the impact of gastric banding on elevated liver enzymes. We
      investigated the role of gastric banding on weight reduction and liver enzymes in
      a cohort of patients with morbid obesity. 198 obese patients (166 female, 32
      male: median age 37 [19-65] years) with BMI 46 kg/m2 were assessed prior to
      gastric banding and 6/12 months postoperative for BMI, ALAT, ASAT, GGT
      respectively. Specific liver diseases were excluded. 37 patients (18.7%) had
      elevated liver enzymes (ALAT 14.1%, ASAT 9.6%, GGT 6.6%) preoperatively. ALAT and
      ASAT returned to normal in all patients postoperatively (p < 0.01). In 14
      patients with significant ALAT-elevation (i.e. > 10% above normal) we found a
      correlation between postoperative fall of ALAT and reduction of BMI within 12
      month (r = 0.4998; p < 0.05). CONCLUSION: 18.7% of morbid obese patients (BMI 46
      kg/m2) have elevated liver enzymes prior to laparoscopic gastric banding. The
      normalisation of elevated liver enzymes correlates to the extent of weight
      reduction after gastric banding. Our data show reversible liver enzyme
      abnormalities, correlating to the degree of obesity.

PMID- 11594120
TI  - [Fecal incontinence: therapy of congenital sphincter dysplasia in adulthood--a
      case report].
AB  - The dynamic graciloplasty has gained acceptance in the therapy of intractable
      fecal incontinence. With a success-rate of 60 to 80%, the dynamic graciloplasty
      is a good alternative towards a permanent colostomy for individual cases.
      Furthermore, adults suffering from congenital anal atresia may be well treated by
      this therapy as described in this case. Following surgery, an accurate follow-up
      is inevitable in these patients, including training of neosphincter control.
      After 8 to 12 weeks the training-process of the neosphincter-control should be
      finished. At this point of time the patient will have obtained defecation-control
      and should be able to execute voluntary defecations.

PMID- 11594121
TI  - [Pregnant HIV infected patient].

PMID- 11594122
TI  - [Comorbidity and physical complaints in morbid obesity].
AB  - The prevalence of obesity is increasing world wide, resulting in morbidity,
      mortality, and reduced quality of life. The aim of this study was to assess
      comorbidities and complaints of subjects with morbid obesity in comparison to
      milder forms of overweight. Therefore, 299 patients visiting our obesity
      consultation were examined and surveyed prospectively. 41% of the subjects were
      morbidly obese showing a significantly higher prevalence of arterial
      hypertension, edema, dyspnea, eczema and depression. Additionally, sleepiness,
      reduced work capacity, physical inactivity, disadvantages in social life and
      disturbed eating habits were observed more frequent. Evaluation of subjects with
      morbid obesity should include a large spectrum of complications, in order to be
      able to offer a comprehensive support and treatment.

PMID- 11594123
TI  - [The practice of compulsory patient commitment].
AB  - In Switzerland civil law allows compulsory hospitalization under defined
      circumstances. It is in the power of municipal authorities to decide on
      compulsory treatment, though in many of the Swiss cantons this power has been
      delegated to physicians. This paper first specifies the requirements for medical
      certificates directing compulsory hospitalization. Then 100 not selected medical
      certificates from 1997-2000 are compared to these requirements. Only 21% of the
      certificates met with all the requirements of form and content, nearly half of
      them showed formal deficiencies. The certificates issued by psychiatrists (n =
      44) turned out to be more correct and complete in form and content than the
      certificates issued by not psychiatric hospital doctors (n = 26) and those issued
      by general practitioners (n = 30). It seems that not specialized (not
      psychiatric) doctors, who are rarely confronted with patients requiring
      compulsory treatment, are overcharged with this delicate and demanding task. To
      blame is also the passivity of the municipal authorities, who do not exercise
      their supervision task and seem to be happy having delegated the delicate problem
      of compulsory hospitalization to physicians.

PMID- 11594124
TI  - [Vacuum needle biopsy of the breast with digital stereotaxic control--initial
      experiences with the Mammotome in Baden].
AB  - The purpose of our study was to evaluate a stereotactic, percutaneous, vacuum
      assisted breast biopsy system. The Mammotome (Biopsies) was used to perform
      breast biopsies in 35 of 37 patients using only one small incision. In two
      patients a biopsy was not possible: one lesion could not be positioned into the
      limited field of the digital CCD-camera. One lesion was not enough dense to be
      seen on digital images. Biopsies were performed because of suspicious
      microcalcifications (34) or nodules (3). Histology revealed 32 benign and 3
      malignant lesions. We encountered 4 syncopes. Because the biopsies are performed
      in the sitting position, they were the cause we had to break up 2 biopsies.
      Relevant hematomas occurred in 4 cases. Vacuum assisted core biopsy has proven to
      be a safe and accurate technique for obtaining a histologic diagnosis in most
      patients who have screening-detected lesions; it is done at a lower cost with
      lower resultant morbidity to the patient compared with traditional surgical
      excisional biopsy. A certain learning phase must be granted.

PMID- 11594125
TI  - [Implementation and testing of a multifunctional electronic patient record for
      routine practice and evaluation of patient care].
AB  - "Medical Monitoring" is a software produced for everyday medical practice in
      order to document data of history, physical and functional status, interventions
      and outcomes. The electronic patient record has been developed for research
      purpose within a network of hospitals and primary care physicians specialized in
      integrative medicine. It should help to realize a comprehensive documentation
      system for long-term observations of patients concerning effectiveness, cost,
      risk and safety. Important components of the program are: a) health record for
      routine documentation in medicine and nursing b) tools for formal assessment in
      special indications c) user-support in service and decision-making d) user
      support for advising and teaching patients in self-treatment and lifestyle
      techniques e) archive-function for diverse findings f) tools for quality
      assurance g) tools for reimbursement and billing.

PMID- 11594127
TI  - [Zoonosis caused by non-domestic animals].

PMID- 11594126
TI  - [Edema and lymphadenopathy. 55-year-old patient with edema and lymphadenopathy:
      significance of fine needle biopsy. Metastatic large cell undifferentiated
      carcinoma of unknown primary tumor (pancreas, stomach, bronchial differential
      diagnosis)].

PMID- 11594128
TI  - [Ethics conflicts in the application of mechanical ventilation: analysis of the
      attitude of critical care and emergency professionals and students].
AB  - OBJECTIVE: To analyze the influence of prognosis, life quality or previous
      instructions in the decision making of applying an invasive
      (intubation/mechanical ventilation), conservative or palliative procedure.
      MATERIAL AND METHODS: "Casuistry" methodology: opinion on the appropriate
      decision regarding five clinical histories representative of ethic conflicts with
      542 health professionals (220 intensive care specialist, 150 emergency department
      professionals, 76 nurses, and 96 students). As control group, 26 students
      enrolled in a International Master on Bioethics. RESULTS: A great inter-group
      variability was observed (p = 0.005) with a higher agreement with control group
      between students and lower with intensivists. The agreement observed was highest
      in cases with "total support" as the appropriate option (kappa 0.85, 0.69, and
      0.66) than in cases with "palliative measures" as appropriate option (kappa 0.22
      and 0.46). CONCLUSIONS: 1) A high variability was observed regarding decisions on
      instituting respiratory support. 2) Decisions regarding the restriction of
      therapeutic efforts are not accepted in the main, even in scenarios merging into
      futility, as permanent vegetative status. 3) Among severely deteriorated and
      handicapped patients, perceived life quality is more appreciated by the patient
      than that estimated objectively. 4) There is no a consensus opinion for the
      respect of previous guidelines of vital support refusal. 5) Age and deep psychic
      deficiency are not considered as cause of discrimination. These features may be
      considered typical of the mediterranean ethics, in which paternalism and charity
      are more appreciated values than autonomy.

PMID- 11594129
TI  - [Systemic necrotizing vasculitis in autopsy].
AB  - OBJECTIVE: To analyze the characteristics of systemic necrotizing vasculitis
      observed in necropsy emphasizing the non-diagnosed cases until necropsy and to
      identify the reasons of clinical confusion. MATERIALS AND METHODS: Necropsies of
      adult patients performed in Hospital General La Paz, Madrid, from 1966 to 1977
      were reviewed. Clinical manifestations, analytical changes and involvement of
      different organs were analyzed. The correspondence degree between clinical and
      necropsic diagnoses was studied. RESULTS: A total of 18 cases of necrotizing
      vasculitis were observed out of 3,980 necropsies. The most common clinical
      manifestations were fever and general syndrome (60%). The organs most commonly
      involved were kidney (94%) and gastrointestinal tract (56%). Diagnosis was
      revealed by necropsy in 39% of cases; in these cases, the incidence of heart
      failure and peripheral neuropathy was significantly lower, whereas digestive
      hemorrhage and liver, pancreas, adrenal gland, and bladder involvement was
      significantly higher. CONCLUSIONS: Systemic necrotizing vasculitis in
      underdiagnosed, which can be partly explained by the lack of specificity of the
      most common symptoms and the paucity of characteristic clinical and organ
      specific manifestations which leads to confusion with more prevalent conditions.

PMID- 11594130
TI  - [Tularemia outbreak in the province of Cuenca associated with crab handling].
AB  - OBJECTIVE: To report the clinical and epidemiologic characteristics of 19
      patients diagnosed of tularemia at our hospital following an epidemic outbreak
      occurred in our health area. METHODS: Retrospective analysis of clinical records
      of patients admitted to our hospital who were examined at the Infectious Diseases
      Clinic and had clinical findings and epidemiologic data consistent with tularemia
      during the period from June 1998 to March 1999. CASE DEFINITION: A patient was
      considered to fulfill the case definition when clinical symptoms, epidemiologic
      data and the following laboratory criteria were met: antibody titer to
      Francisella tularensis (tube agglutination test) > or = 1/128 in the
      convalescence serum specimen, seroconversion or recovery of the microorganism
      from biological material. RESULTS: Nineteen patients with a median age of 60
      years. Males predominated (63.1% male patients); all of them had handled red
      crayfish from the same source (rio Mayor). The incubation period ranged from 0 to
      15 days (mean 4.88 days). All patients presented with the ulceroglandular form.
      Seventy-three percent of patients received doxycycline. Only one patient
      relapsed. Water samples from the reservoir of the depuration plant of the river
      were positive to F. tularensis by PCR. This same result was confirmed in stomach
      and hepatopancreas of crayfish fished in rio Mayor in the second half of July.
      CONCLUSIONS: The most likely hypothesis of this outbreak was the contamination of
      the river water with animals dead from tularemia which, together with the
      characteristics of the transmission mechanism (wounds caused by crabs) had
      contributed to the acquisition of this disease in humans. Interestingly too, red
      crayfish as the source of infection.

PMID- 11594131
TI  - [Anemia secondary to lead poisoning. Our experience with 12 cases].
AB  - BACKGROUND: A decrease in hemoglobin production is probably the main cause of
      anemia observed in patients poisoned by lead although hemolysis caused by the
      effects on membrane or by inhibition of other enzymes such as 5'-pyrimidine
      nucleotidase may also play a key role. The main lead exposure source comes from
      lead use in industry; however, outside occupational exposure, food and water
      consumption is the main cause of lead exposure. MATERIALS AND METHODS: Clinical
      and analytical characteristics are reported of twelve patients with lead
      poisoning of food and water source occurred in the last 14 years in two health
      areas in north Extremadura. RESULTS: The exposure source was wine, vinegar and
      olives in one case, hand-made brandy in five, water consumption in houses with
      lead piping, and in two cases the cause was not determined. The clinical picture
      was similar in all cases with the exception of one female patient who had
      encephalopathy and hepatic failure. Diagnosis was suggested by regenerative
      anemia with basophilic stippling of erythrocytes. All patients received oral
      calcium disodium EDTA. CONCLUSIONS: Lead poisoning in non-industrial areas is a
      rare entity. Nevertheless, owing to the use of artisanal procedures for wine
      elaboration and derivatives, its occurrence is increasing. In a patient with
      symptoms of lead poisoning and regenerative anemia, a peripheral blood smear
      should be reviewed.

PMID- 11594132
TI  - [Treatment of chronic constipation].

PMID- 11594133
TI  - [Indications for lung transplantation].

PMID- 11594134
TI  - [Reconsidering renal biopsy in primary glomerulonephritis].

PMID- 11594135
TI  - [Atypical clinical manifestations of pneumonia in the elderly].

PMID- 11594136
TI  - [Enteral nutrition in the home of the patient in 2001].

PMID- 11594137
TI  - [Lung infiltration and skin lesions. Varicella pneumonia].

PMID- 11594138
TI  - [Otitis media and bacteremia. Thrombosis of the lateral sinus secondary to acute
      otitis media].

PMID- 11594139
TI  - [A 63-year-old male with general syndrome and splenic mass].

PMID- 11594140
TI  - [Interstitial lung involvement in a 41-year-old woman with pneumothorax history].

PMID- 11594141
TI  - [Erythema and hand desquamation. Paraneoplastic acrokeratosis (Bazex syndrome)].

PMID- 11594142
TI  - [Treatment of chronic obstructive pulmonary disease].

PMID- 11594143
TI  - [Pleural effusion as presentation form of multiple myeloma].

PMID- 11594144
TI  - [Acute appendicitis as presentation form of intestinal tuberculosis].

PMID- 11594145
TI  - [Celiac disease: "another great imitator"].

PMID- 11594146
TI  - [RS3PE syndrome associated with prostatic adenocarcinoma].

PMID- 11594147
TI  - [High CA-125 titer in chronic hepatopathy].

PMID- 11594148
TI  - [Treatment of heart failure. Role of the cardiologist].

PMID- 11594150
TI  - [New gestagens--advantages and disadvantages].
AB  - Due to their high oral bioavailability synthetic progestagens are used for
      therapy, hormone replacement therapy and contraception There are different types
      of progestogens. There are progesterone derivatives, nortestosterone derivatives
      (13-methyl-gonanes and 13-ethyl-gonanes), spirolactone derivatives and
      norpregnance derivatives which differ in their efficacy and hormonal profile. All
      progestagens show antiestrogenic activities, inhibit the estrogen-induced
      proliferation of the endometrium and, hence, decrease the risk of endometrial
      hyperplasia. With the exception of Dienogest, the derivatives of 19
      nortestosterone are characterized by a 17-alpha-ethynyl group and show slight
      androgenic properties which may antagonise some estrogen-dependent alterations of
      hepatic serum parameters. Tibolone which is a derivative of norethynodel also
      belongs to this group. Among the nortestosterone derivatives, there are the so
      called "Prodrugs". Prodrugs are rapidly transformed after intake to the active
      progestagens. Progesterone derivatives partly exert moderate androgenic or
      antiandrogenic effects, while the spirolactone derivative Drospirenone shows
      antimineralocorticoid and antiandrogenic activities. The progesterone derivatives
      as well as Gestodene and Desogestrel have certain glucocorticoid activities
      which, at the doses used, are not clinically relevant, but possibly may influence
      vascular function. The effects of 19-norpregnane derivatives are comparable with
      those of progesterone derivatives. According to their different hormonal profiles
      and activities, the various available progestogens allow the choice of
      preparations which are best suitable for the individual woman for contraception
      or hormone replacement therapy.

PMID- 11594151
TI  - [Hormonal contraception for adolescents].
AB  - The new hormonal contraceptives are safe, effective and with fewer side effects
      than the older formulations. Their incidence of serious complications is low,
      particularly as compared to the health risk related to pregnancy. Adolescents
      must be screened for contra-indications before giving them a hormonal
      contraceptive. Because pills do not prevent sexually transmitted diseases,
      teenagers should be counselled to use a barrier methods together with COCs. Young
      girls need frequent follow-up and close monitoring to minimise side effects and
      to increase compliance and continuation in use. Long-term contraception by
      implants represents a valid alternative option with an increasing popularity
      among adolescents.

PMID- 11594152
TI  - [Postcoital emergency contraception].
AB  - The actual methods of postcoital emergency contraception are described and
      compared. The method of choice is the administration of a progestagen-only pill
      because this method is more reliable and effective than the use of a combined
      estrogen-progestagen pill ("Yuzpe-Method"), and because the incidence of side
      effects is considerably lower. The results obtained with levonorgestrel alone are
      presented by the authors. The postcoital introduction of a copper intrauterine
      device is highly effective, but invasive. This method is indicated if it is too
      late to use the pill. An open and accepting setting of the consultation and a way
      of taking the medical history that is pointing to the auto-responsibility are
      essential, especially for adolescents. Low conditions for the admission to the
      counselling are postulated, and the obligation to possess a medical prescription
      to obtain the only progestagen-only pill is questioned.

PMID- 11594153
TI  - [Low-dose oral contraception and bone density].
AB  - Oral contraceptives (OC) with 20 or 30 mcg Ethinyl-Estradiol (EE) inhibit bone
      remodeling in all age groups investigated until today as far as the biochemical
      parameters are considered. In perimenopausal women, OC with 20 or 30 mcg EE
      reduce the decrease in bone density and may, depending on the starting point,
      induce an increase in bone density. OC with 20 mcg EE might impede the formation
      of a physiological peak bone mass in very young women (probably women less than
      20 years of age) by a reduction of bone metabolism. This possibility provoked a
      certain insecurity. However, it should not lead to the consequence that a safe
      contraceptive method is refused to young women. Unfortunately, there is still a
      lack of reliable studies allowing a final statement on the effect of low-dose OC
      on bone density in teenagers. Such studies are urgently needed so that we are
      able to guarantee in very young women that a reasonable contraception has not to
      be payed by a long-term risk for the skeletal health. The administration of a
      progestagen-only pill might be an alternative method for contraception in
      adolescence. A preparation containing 30 mcg of Levonorgestrel, nearly out of use
      today, could be of particular interest. A British study (20) has shown that
      during regular peroral administration of 30 mcg Leveonorgestrel per day, mean
      serum estradiol concentration decreased only slightly, from 653 to 500 pmol/l.
      This Estradiol concentration should still allow a normal bone metabolism and
      therefore a normal formation of the peak bone mass. However, the data actually
      available do not point convincingly to the conclusion that OC with 20 mcg EE or
      less might result in an insufficient estrogen concentration for normal bone
      metabolism. To reach peak bone mass, other factors than estrogens only are
      needed, such as Calcium, Vitamin D and physical activity.

PMID- 11594154
TI  - [Contraception in immigrant women].
AB  - The contraceptive behaviour of immigrants is not enough reliable if the great
      number of abortions is considered. Possible explanations for this fact are
      immigration itself but also the cultural background. Within the practical
      guidelines for transcultural contraceptive counselling, the most important points
      are a low access limit, the use of translators and mediators familiar with the
      subject, enough time and a high motivation.

PMID- 11594156
TI  - [Cardiovascular risks associated with low-dose combined oral contraceptives].
AB  - The relative risk for cardiovascular events in current users of low-dosed oral
      contraceptives is about 2- to 3-fold greater than in nonusers. As in young women
      (age 20-24) the incidence for cardiovascular events is very low (51 per million
      woman-years) the use of modern oral contraceptives is safe in the absence of a
      history of smoking, hypertension, migraine, venous thromboembolism in the
      personal or family history and in the absence of other conventional risk factors.
      The cardiovascular risk is increased in women older than 35 years. This risk
      increases 2- to 4-fold if oral contraceptives are used and is substantially
      elevated in combination with additional cardiovascular risks. To minimize these
      risks it is essential to take a careful personal and family history and to check
      the blood pressure. Women with cardiovascular risks should be encouraged to use
      other forms of contraception, like progestagen-only methods or intrauterine
      devices.

PMID- 11594155
TI  - [Hormonal contraception in the perimenopause].
AB  - Perimenopause, such as postmenopause, is a physiologic condition that could be
      accompanied by several symptoms that may need a medical intervention. Women need
      to be informed about the available therapeutic options, including no treatment at
      all if not necessary. Oral hormonal contraceptives represent a valid and safe
      option in healthy premenopausal women with complaints. They guarantee a safe and
      reliable contraception in women without contraindications. The alternatives to
      oral hormonal contraceptives are injectable progestagens, oral progestagen-only
      preparations, progestagen implants or progestagen-loaded IUD's. It is highly
      important to inform correctly the patient and make her to participate actively in
      the therapeutic decision. This educational process helps in building a solid
      relationship and improves patient adherence with better clinical results.

PMID- 11594157
TI  - [School performance: a question that divides. Analysis of learning difficulty].
AB  - The difficulty of learning is getting always more important, also in relation of
      a better knowledge of these problems. One factor which has to be taken in
      consideration as the behaviour of the school.

PMID- 11594158
TI  - [Adolescence and family life cycle. Role of the pediatrician].
AB  - Adolescence observed as one of the step of the life cycle from the point of view
      of changes in the family. The role of paediatricians in the conversation with the
      adolescent and his parents is to pay attention to the influence that the whole
      family system could have on producing symptoms.

PMID- 11594159
TI  - [They way adolescents live at home].
AB  - The kids, observing the relationship of their parents, are learning from them.
      Today the home is less home for everyone. At home you are eating, you are
      learning, especially you are watching a lot of TV. Often there is non a lot of
      trust between each other. Because of this the conversation is necessary and not
      the control of the adolescent secretly.

PMID- 11594160
TI  - [Advanced adolescence].
AB  - The advanced adolescence is the one after the eighteenth birthday. The adolescent
      tries to accomplish 3 engagements: 1. social and economic stability, 2. the
      research of a system of values, 3. record of concepts.

PMID- 11594161
TI  - [Eating disorders in adolescence: anorexia in children].
AB  - When doctor visits adolescents have to pay attention to the massage of body like
      a mirror of difficulty about growth. Adolescents change their eating habits
      because they need to distinguish to the family. The doctor have to see first
      signals of more serious behaviour join to eating: anorexia nervosa.

PMID- 11594162
TI  - [Adolescence and alcohol abuse. Relevance of information given by the
      pediatrician].
AB  - Often we don't see alcohol abuse among adolescents, but this kind of drug, easy
      to find, could be used to trying their limits. Contemporary group has an
      important role in the habit of drinking. Often family don't think that it's real
      problem and it's important that paediatrician grasp this dangerous signals.

PMID- 11594163
TI  - [Surgery of congenital malformations in developing countries: experience in 13
      humanitarian missions during 9 years].
AB  - The authors report their surgical experience concerning seriously impaired
      children due to congenital malformations or other non-congenital anomalies such
      as burns and traumas. All the patients were operated in one of 13 humanitarian
      missions undertaken in four developing countries. Throughout the "Third World"
      the demand for reconstructive surgery is extremely high due to the high birth
      rate and consequently large number of patients, as well as the shortage of both
      medical staff and supplies. In developing countries Primary Health Care has
      always been considered a priority and so hospitals, which are used mainly for
      emergency operations, are usually few in number and badly equipped; elective
      surgery is considered a luxury. Children with congenital diseases and/or other
      non-congenital anomalies who are fortunate enough to reach a hospital will often
      be treated by general surgeons lacking specific training; those children
      suffering from disabling conditions are often neglected and left to live with
      their anomalies for the rest of their lives. Our surgical missions have always
      been undertaken at the request of Catholic missionaries and/or secular
      organizations which contribute to the individual health schemes of each country.
      Highly experienced volunteer staff took part in the missions; medical teams are
      made up of 2 surgeons, one or two anaesthetists and two scrub nurses. The
      assistance and cooperation of local medical staff was essential in the
      preselection of cases to be operated while each single medical team provided all
      the necessary supplies for surgery, which took place in small but well-equipped
      missionary hospitals provided by the local authorities. A total of 1140 children
      were operated on during the 13 missions: 32% of these had routine procedures
      performed in day surgery and 54% underwent major plastic and reconstructive
      surgery for facial, uro-genital and anorectal malformations or for serious
      consequences of burns or traumas. The proportion of emergencies was only 3% as
      these were normally excluded because of the short duration of the missions. 26
      patients had to be reoperated as a result of complications or surgical failure
      and long-term follow-up provided by either the local staff or as a part of later
      missions was given in over 70% of the major surgery performed. On the whole, the
      surgical results were highly satisfactory even if a final evaluation should be
      made taking the cultural factors and the socio-environmental conditions of each
      individual country into consideration. Such an evaluation should most importantly
      be made on the basis of the well-being of the patient, general satisfaction of
      the families involved and improved quality of life of these children.

PMID- 11594164
TI  - [Medical treatment of cryptorchism. "Vanitas vanitatum et omnia vanitas"].
AB  - Aiming to study the effectiveness of medical therapy in cryptorchidism, a
      computerised Medline research from 1985 to 1999 on the thesaurus word
      "cryptorchidism" with the filter "drug therapy" was conducted. Of the 147 papers
      thus retrieved, only those dealing with more than 50 patients were considered.
      Factors studied were: ultimate aims of therapy, different drugs and/or
      associations used, suggested age of treatment, dosages and cycles, anatomical
      position of the testis, mono- or bilaterality of cryptorchidism. For every
      considered factor results heavily conflicting were found. According to the
      various Authors, medical treatment has different goals: not only to induce
      testicular descent but also to improve testicular trophism, to help in diagnosis
      and/or in surgical treatment, to increase postsurgical fertility, to reduce
      neoplastic risks, to reduce the psychological stress. About relative
      effectiveness of drugs, hCG seems to be more effective than LH-RH in most papers;
      the latter resulted slightly more effective than placebo (from 37% vs 18% to 9%
      vs 8%). Suggested age for treatment goes from less than 6 months to more than 6
      years. In relation to the position, non palpable testes resulted almost uniformly
      not responding to the therapy, while testes in prescrotal position responded from
      17% to 100%. According to the mono- or bilaterality of the lesion, results vary
      respectively from 58% vs 50% to 14% vs 64%. Relapse rate as well shows a
      variability from 10% to 63%; effectiveness of a second treatment in such cases
      goes from 0% to 100%. Drawing definite conclusions from this analysis turned out
      to be impossible because of the steady high variability in published results,
      leaving at the end of the day an unappealing sensation of "vanitas" (vacuity).

PMID- 11594165
TI  - [Complications of Meckel's diverticulum].
AB  - The Authors describe a case of gastrointestinal bleeding from a Meckel's
      diverticulum due to acid production by the heterotopic gastric mucosa and a case
      of bowel obstruction for the presence of a Meckel's diverticulitis. Diagnostic
      difficulties and choices of surgical therapy are then discussed.

PMID- 11594166
TI  - [Headache as atypical presentation of celiac disease: report of a clinical case].
AB  - Coeliac disease (CD) is a gluten dependent enteropathy with genetic
      predisposition. The introduction of the gluten with the diet leads to a damage of
      the intestinal mucosa losing the ability of absorption. Together with the
      "classic forms", in wich the intestinal symptomatology is prevalent, there are
      atypical forms, with unusual clinical presentation and silent forms with no
      clinical symptoms. The neurologic symptoms are not frequent and regard seizures,
      headache, ataxia and psychiatric problems. We report on a patient with headache
      since 3 years of age in which the headache the only manifestation of CD. The
      diagnosis of CD was made at 11 years, when he came at our observation for
      episodes of headache. Also the older sister is found affected by CD. After three
      months of gluten free diet, it was obtained the complete resolution of the
      headache. Also if the pathogenesis of the headache in patient with CD is unknown
      we think that a autoimmune, vascular or blood flow mechanism could be
      ipotizeable.

PMID- 11594167
TI  - [Report of a case of primary ciliary aplasia].
AB  - We report a case of one boy with ciliary aplasia characterized by diagnostic
      peculiarity, consisting in the initial non-diagnosis, a period of relative well
      being and a relapse with good recovery after adequate therapy.

PMID- 11594168
TI  - [In vivo and in vitro production of interleukin-1 after febrile convulsions].
AB  - Pathogenesis of febrile convulsions (FC) is still unknown, suggested causes
      include the role of antidiuretic hormone (ADH). ADH is an endogenous antypyretic
      and his excessive production of the consequent hyponatraemia may be the cause of
      FC in children with susceptibility to this type of seizure. Whereas, interleukin
      1 (IL1) is a pyrogenic substances and is involved in the release of AVP. Helminen
      et al. have reported a significantly higher production of IL1 in culture of
      peripheral blood monocytes stimulated with lipopolysaccharide (LPS) of children
      with FC than in the others with fever but without convulsions. More recently
      Lahat et al. have compared plasma and cerebrospinal fluid ILI levels of children
      with FC with those of children with fever but without convulsions, but they did
      not find significant differences. The aims of this study were to determine the
      IL1 levels in vivo and in the supernatants of cultures of peripheral blood
      mononuclear cells (PBMC) stimulated or not with LPS in children with FC and in
      children with fever without FC and to evaluate the influence of ADH and diazepam
      (DZ) on IL1 production. Blood samples for PBMC cultures were obtained from 11
      children with FC on the hospital admission, (group 1) and after 48 hours from
      treatment with DZ (group 2). The production of IL1 was measured by RIA in the
      supernatants of the PBMC stimulated with LPS, LPS + DDAVP (synthetic
      vasopressin), LPS + DZ and in vivo in plasma samples. The control groups were
      constituted by 9 children with fever and without convulsions (group 3), 4 of them
      were studied at the end of fever too (group 4), and finally by 9 children in good
      health (group 5). No significant differences were observed. These results do not
      support the hypothesis that increased production of IL1 is involved in the
      pathogenesis of FC in children.

PMID- 11594169
TI  - Lumbo-sacral agenesis. Clinical analysis and treatment relating to 4
      observations.
AB  - Lumbo-sacral agenesis fall within the framework of numerical anomalies by default
      of the vertebral column. They are characterized by a more or less significant
      absence of vertebrae of the sacral, lumbar and, less frequently, thoracic
      regions. They are grouped in Foix and Hilleman's "crural-vesical-gluteal
      dystrophy syndrome". It was Ranshaw and Stanley who first proposed a
      classification of sacral and lumbo-sacral agenesis into 3 groups. Being difficult
      to refer strictly to such a classification, the Authors divide their series of 56
      cases of sacral agenesis into 3 groups, putting total sacral agenesis with
      different degrees of lumbar and thoracic agenesis into the first group and
      describing the treatment of 4 cases included in this group. The follow-up of the
      mentioned cases leads to the following considerations: 1. From the embryonal
      point of view, this pathology comes within the "caudal regression syndrome". Such
      regression, as first referred by Duhamel, results excessive in these cases. 2.
      Maternal diabetes seems to be the dominant etiology. 3. Accurate clinical and X
      Ray examination must be carried out before establishing the therapeutic iter, as
      prognosis depends on the instability of the rachis, the mobility of the hips as
      well as on the flexibility of the knees. 4. In view of improving functional
      possibilities and giving the patient maximum autonomy, both in sitting and
      standing positions, two types of interventions are envisaged: fixation of the
      spine correction of the lower limbs.

PMID- 11594170
TI  - [Children are born twice: at birth and in adolescence. The adolescent, his/her
      parents, and the pediatrician].
AB  - We know the young's problem often depended to family and to society. In these
      years we have seen important changes of the family, that is no more a
      "patriarchal family" but is a "nuclear family". In general we can say that there
      is a change of the social levels of the family; in particular the Mass-media
      (especially television-set) are the most important factors responsible of these
      changes in fact they block the dialogue between family's members. In Italy we can
      found about 4.500.000 of adolescents (with age between 14 and 20 years). If we
      observe recent epidemiological data, we can suppose that: about 500.000 of young
      men have or will have problems that block them to live serenely their adolescence
      about 70.000 of young men have had a so important problem than they have a
      psychiatric personality in the future about 4.000 of young men will die for
      suicide, drugs or for road's incidences. For adolescents is necessary a doctor
      with multiple competence. We think that this doctor can be pediatrician because
      he is the doctor that visit children from neonatal age and, for this reason, ha
      can identify the "family with problems". In conclusion we can say that the
      pediatrician could say to adolescent's patents that "it is born a new child" with
      personal idea and with different attitudes, for these reason they must change the
      rules that they used before puberty because now the same rules are no more valid!

PMID- 11594171
TI  - A critical analysis of the pharmacology of AZT and its use in AIDS.
AB  - The triphosphorylated form of the nucleoside analogue 3'-azido-3'-deoxythymidine
      (Zidovudine, AZT) is claimed to interrupt the HIV replication cycle by a
      selective inhibition of viral reverse transcriptase, thereby preventing the
      formation of new proviral DNA in permissive, uninfected cells. Given that initial
      HIV infection of an individual instigates abundant HIV replication from inception
      until death, and that the life of infected T-cells is only several days, the
      administration of AZT should lead both in vitro and in vivo (i) to decreased
      formation of proviral DNA; and thus (ii) to decreased frequencies of 'HIV
      isolation' (detection of p24 or reverse transcription or both) in stimulated
      cultures/cocultures of T-cells from seropositive individuals; (iii) to decreased
      synthesis of HIV p24 and RNA ('antigenaemia', 'plasma viraemia', 'viral load')
      ultimately resulting in low or absent levels of all three parameters; and (iv) to
      a perfect and direct correlation between all these parameters. A critical
      analysis of the presently available data shows that no such evidence exists, an
      outcome not unexpected given the pharmacological data on AZT. HIV experts all
      agree that only the triphosphorylated form of AZT (AZTTP) and not the
      unphosphorylated form administered to patients, nor its mono- or diphosphate, is
      the active agent. Furthermore, the mechanism of action is the ability of AZTTP to
      halt the formation of HIV-DNA (chain termination). However, although this claim
      was posited from the outset, AZT underwent clinical trials and was introduced as
      a specific anti-HIV drug many years before there were any data proving that the
      cells of patients are able to triphosphorylate the parent compound to a level
      considered sufficient for its putative pharmacological action. Notwithstanding,
      from the evidence published since 1991 it has become apparent that no such
      phosphorylation takes place and thus AZT cannot possess an anti-HIV effect.
      However, the scientific literature does elucidate: (i) a number of biochemical
      mechanisms which predicate the likelihood of widespread, serious toxicity from
      use of this drug; (ii) in vitro data proving that AZT has significant
      antibacterial and antiviral properties which confound interpretation of its
      effects when administered to patients. Based on all these data it is difficult if
      not impossible to explain why AZT was introduced and still remains the most
      widely recommended and used anti-HIV drug.

PMID- 11594172
TI  - [Alveolar-arterial gradient of oxygen in COPD patients].

PMID- 11594173
TI  - [Alveolar-arterial gradient of O2 in COPD with hypercapnia].
AB  - OBJECTIVE: This study was conducted to assess whether or not calculation of the
      alveolar-arterial oxygen tension difference (AaPO2) from arterial blood gas
      measurements, breathing air, is useful to discriminate patients with hypecapnia
      associated with obstructive lung disease. PATIENTS AND METHODS: The effect of
      different values for the respiratory exchange ratio (R) was also analyzed. We
      calculated the AaPO2 in 45 patients with chronic airway obstruction and
      hypercapnia (PaCO2 in 45 mmHg) and hemodynamic stability using the standard
      alveolar gas equation, PAO2 = PIO2 - PACO2 [FIO2 + (1-FIO2)/R], with R assumed to
      vary from 0.6 to 1.1 and the simplified alveolar gas equation, PAO2 = PIO2 -
      PACO2/R, with R assumed to be 0.8. It was considered that a patient was correctly
      classified when the calculated AaPO2 was greater than predicted AaPO2. RESULTS:
      When the simplified alveolar gas equation was used, 9 (20%) of 45 patients were
      misclassified, whereas using the standard equation with R assumed to be 0.8, 41
      (91%) of 45 patients were correctly classified. Modification of the value of R
      only allowed improving the classification of two further patients. CONCLUSIONS:
      We conclude that calculation of the AaPO2 using the standard equation and R = 0.8
      can be used to classify hypercapnic COPD patients. This laboratory parameter is
      of sufficient discriminant value to be used for clinical purposes.

PMID- 11594174
TI  - [Osteoporosis in patients admitted to an internal medicine service of a
      university general hospital].
AB  - OBJECTIVE: To ascertain the incidence of osteoporosis and epidemiological factors
      in patients admitted to an Internal Medicine Service of a University General
      Hospital in Madrid, Spain. We also took into account the reasons for admission,
      associated diseases, and the preventive and therapeutic diagnostic implications.
      PATIENTS AND METHODS: The analytical, descriptive, retrospective and transversal
      study of one hundred patients over fifty years of age admitted to an internal
      medicine service during 1997, obtaining in addition to the clinical discharge
      report, epidemiological data with regard to the radiological diagnosis of
      osteoporosis, the reason for admission, past history, the prevention and
      treatment of the initial complaint as well as the osteoporosis previous
      diagnosis. RESULTS: 26% of those patients included in the survey had radiologic
      criteria of osteoporosis although only in 1 per cent of them had osteoporosis
      been diagnosed previously. The main risk factors, apart from the age and sex, are
      the associated illnesses which cause malnutrition and immobilization, and the use
      of drugs, especially heparin. CONCLUSIONS: Osteoporosis is a condition common in
      patients above 50 especially women, who are admitted to an Internal Medicine
      Service. A quarter of those patients admitted have osteoporosis. Very few are
      diagnosed and treated. In this group of patients apart from the habitual risk
      factors, are added those for the associated disease generally chronic, and the
      treatment they receive. During their stay in the hospital osteoporotic patients
      are three times more likely to receive heparin and other drugs which aggravate
      osteoporotic, than non osteoporotic patients. For that reason the risk of
      fractures is greater and the need for prospective diagnostic studies is even more
      necessary in this group of patients.

PMID- 11594175
TI  - [Pneumonia in the aged patient: is the clinical presentation atypical?].
AB  - OBJECTIVE: Some new studies have questioned the often atypical character of
      pneumonia in aged patients. Therefore to study the different clinical
      presentation of this pathology is our aim. MATERIAL AND METHODS: Retrospective
      analysis of 179 cases of pneumonia in patients aged older than 65 years who were
      admitted in our hospital during 1992. RESULTS: The average age of the patients
      was 78 years, being 65.9% of them men. 91% presented pneumonias acquired in the
      community. 73.1% showed a typical dominant clinical presentation (febrile
      respiratory); respiratory (47.4%), febrile (25.7%). The rest presented atypical
      patterns; mental-neurologic or "cerebral dysfunction" (10.6%), perambulation
      general state (6.15%) and digestive-abdominal (9.5%). The respiratory pattern was
      associated to the presence of respiratory antecedents (p < 0.001); the febrile
      pattern to the absence of cardiovascular antecedents (p < 0.05); the mental
      neurologic to the presence of neurologic antecedents (p < 0.001) and the
      alteration of perambulation-general state to an evolution of more than 7 days (p
      < 0.05). CONCLUSIONS: The greatest number of our pneumonia patients older than 65
      years follows a typical clinical pattern febrile-respiratory). The patient's
      prior pathology conditions the clinical presentation.

PMID- 11594176
TI  - [Determination of antibodies against A-60 antigen for diagnosis of M.
      tuberculosis infection. A useful tool for rationalization of chemoprophylaxis in
      HIV patients].
AB  - OBJECTIVE: To identify M. tuberculosis infection in HIV patients by use of PPD
      and an ELISA test detecting the presence of antibodies against antigen A-60 of M.
      bovis. METHODS: 116 incoming HIV patients were classified according to the CDC.
      The status of M. tuberculosis infection was probed with PPD (RT-23) and the state
      of anergy was estimated by a Multitest CM1 (Multitext). The presence of
      circulating antibodies of the IgG class against antigen A-60 was analysed by an
      ELISA. The clinical course of the patients was followed for 24 month. RESULTS: A
      positive serology (A-60) was found in 52.58% of the patients, coinciding with
      70.45% of the positive PPD (p < 0.003). This statical observation was found when
      we studied all of the individuals, and those with more than 500 CD4 lymphocytes.
      The Multitext was positive in 11.11% of the patients with PPD (-), all of them
      without antibodies against A-60. However, 42.2% of the patients who were PPD and
      Multitext (-), had circulating antibodies against A-60. The following up of the
      patients during 24 months allowed the detection of 7 news cases of pulmonary
      tuberculosis, 4 of them had a positive A-60 serology, and 4 were anergy.
      CONCLUSIONS: HIV patients with M. tuberculosis infection have circulating
      antibodies against A-60 antigen of M. bovis with independence of their immunity
      status. In anergic patients the presence of this antibodies can be an useful tool
      for rationalizing the prophylaxis against M. tuberculosis. A seropositivity (A
      60) indicates as well as does PPD a previous contact with M. tuberculosis.

PMID- 11594177
TI  - [Possible prognostic value of arterial hypertension in postmenopausal women with
      breast cancer in complete clinical remission. Pilot study].
AB  - BACKGROUND: The objective of this work was to determine the blood pressure of
      postmenopausal women with breast cancer in complete clinical remission of long
      duration. MATERIAL AND METHODS: It in a pilot study of case and controls, in
      which we measure the Blood Pressure (BP) of 83 postmenopausal women, with breast
      cancer histologically confirmed, in complete clinical remission of long duration,
      recruited by consecutive sampling, to compare it with that of 70 normal
      postmenopausal women of the same age used as controls. They ara calculated the
      body mass index (BMI), the corporal surface, the confidence intervals (CI) of the
      means, the correlation between the BMI and the BP in both groups (breast cancer
      patients and normal control) and between the free disease interval and the
      systolic and diastolic blood pressures. RESULTS: The mean of the systolic BP in
      93 breast cancer patients in complete clinical remission was 163 mm Hg (95% CI
      155-171) and in 70 normal controls was 134 mm Hg (95% CI 129-139). The difference
      between both groups in statistically significant (p < 0.001). The mean of the
      diastolic BP in the breast cancer patient in complete remission it was 98 mm Hg
      (94-104) and in the normal controls was 78 mm Hg (74-82). The difference between
      both groups was statistically significant (p < 0.001). CONCLUSIONS: This arterial
      hypertension, independent of the BMI and from the duration of the free disease
      interval, is associated with a long duration of the complete remission in
      postmenopausal breast cancer patients and consequently with a good prognostic of
      this disease.

PMID- 11594178
TI  - [McArdle disease: report of four brothers with myophosphorylase deficiency].
AB  - Myophosphorylase deficiency, or McArdle disease, is an uncommon entity. The gene
      for human myophosphorylase has been cloned and is located on chromosome 11, in
      keeping with the autosomal recessive nature of the disease and there is an excess
      of male patients. The diagnosis is established by documentation of elevated
      glycogen content and reduced phosphorylase activity in biopsied muscle tissue. We
      report four cases with McArdle disease which were 16, 15, 11 and 5 years old.
      They were brothers, and they came to the hospital because of pain, cramps and
      myoglobinuria after exercise or infection; in the first case, a male patient,
      myoglobinuria caused acute renal failure. Three of them showed reduced
      phosphorylase activity in biopsied muscle tissue. We discuss the different
      therapeutic possibilities.

PMID- 11594179
TI  - [Asthma as presentation form of relapsing polychondritis].
AB  - Relapsing polychondritis is a systemic disease of unknown etiology characterised
      by relapsing inflammation affecting cartilaginous structures, cardiovascular
      system, eyes and ears. Respiratory involvement occurs in 56% of patients during
      the disease progression, but only in 14% of cases as an initial presentation.
      Patients develop severe symptoms due to the disease affecting the glottis and the
      tracheobronchial tree, which represents the cause of death in 50% of cases. The
      unspecificity of respiratory symptoms makes that the disease may be confounded
      with some other if it is not accompanied with a typical presentation, which may
      cause a delay in the diagnosis. Pulmonary function tests are of great importance,
      since an obstructive pattern not reversible after bronchodilator administration
      and a plateau in flow-volume curves are of great help when assessing the severity
      of the obstruction. High resolution computed tomography is a non-invasive test
      more precise than bronchoscopy in identifying tracheal and bronchi abnormalities,
      so it should be performed at the onset of the respiratory symptoms together with
      the pulmonary function tests. We present the case of a patient, whose disease
      started with respiratory semiology suggesting bronchial asthma, which preceded in
      six months the main sign nasal chondritis.

PMID- 11594180
TI  - [Systemic lupus erythematosus with retractile mesenteritis and catastrophic
      antiphospholipid syndrome].
AB  - The Antiphospholipid Syndrome coexisting with Lupus has been associated to wide
      variety of clinical manifestations, mostly linked to focal ischaemia or
      infarction. Acute multi-organ failure occurring in patients with these
      autoantibodies is named Catastrophic Antiphospholipid Syndrome because the high
      mortality. On the other hand, the term Retractile Mesenteritis is applied to the
      circumstance in which, an chronic inflammatory process with thickening and
      infiltration of the mesenterium occur, due to ischaemic mechanism, among many
      other multiple causes. We describe one patient with concomitance of
      Antiphospholipid Syndrome, evidence of abdominal ischaemia and Retractile
      Mesenteritis. The patient developed Catastrophic Antiphospholipid Syndrome,
      probably due to infectious process and, antithrombotic therapy suppression
      because upper gastrointestinal bleeding, and dead.

PMID- 11594181
TI  - [Massive pleural empyema caused by pyonephrosis].
AB  - The pleural empyema has unusual origin at extralung causes. Then, is essential to
      identify the primary process in order to obtain the clinical setting control.
      Previously described, but even exceptional, this case report show an empyema in
      which it's origin was an asymtomatic pyonephrosis, caused because of a big kidney
      calculus and it's discovery was suspected by the bacillus results. The treatment
      must include appropriate antibiotic therapy and thoracic drainage, and also the
      drain of the purulent accumulations at the kidney and perikidney area.

PMID- 11594182
TI  - [Spontaneous pneumothorax and active pulmonary tuberculosis].
AB  - We report three HIV-negative patients with spontaneous pneumothorax as clinical
      manifestation of active tuberculosis acute chest pain and dyspnea was the cause
      of admission. Chest roentgen grams showed lung collapse and parenchymal
      cavitation in two of therm and hydropneumothorax in the other. Outcome was
      favorable with antituberculous drug therapy and placement of chest tube. Although
      spontaneous pneumothorax is frequent in fibrosis pulmonary tuberculosis, it
      seldom complicated active tuberculosis in spite of increase of its incidence.

PMID- 11594183
TI  - [Leptin: physiological and clinical role].
AB  - Leptin is a protein that has been identified three years ago, but its role, or at
      least its deficiency, was suspected from 1950. Dickie and coworkers reported the
      appearance of a mutant rat in one of their colonies with morbid obesity. The
      genetic defect was autosomal recessive and was manifested early in life. In
      December 1994, the gen ob was cloned, which stated the first step for the later
      identification of the gen product leptin, as a protein of 167 aminoacids
      expressed in adipose tissue. Since then, leptin has been implicated in many
      neuroendocrine regulatory pathways. The recent research in leptin roles worth an
      update review, and so its current and future clinical relevance.

PMID- 11594184
TI  - [Multiple myeloma lambda IgG: myelomatous pleural effusion, an unusual
      presentation].

PMID- 11594185
TI  - [Maxillary osteolysis, bacillary angiomatosis in HIV infection].

PMID- 11594186
TI  - [Intramedullary metastasis of a non microcytic lung carcinoma].

PMID- 11594187
TI  - [Secondary coma from atropine poisoning].

PMID- 11594188
TI  - [Bronchospasm from heroin inhalation].

PMID- 11594189
TI  - [The short-stay medical unit of A Coruna: 5th anniversary].

PMID- 11594190
TI  - [Apropos of a special consult on arterial hypertension].

PMID- 11594191
TI  - [Turner's syndrome with isochromosome X: delayed diagnosis].

PMID- 11594192
TI  - [Acute abdominal pain in the elderly].

PMID- 11594193
TI  - [Systematic paradoxical response to tuberculosis treatment: apropos of a case].

PMID- 11594194
TI  - [HMG-CoA reductase inhibitors and sexual dysfunction].

PMID- 11594195
TI  - Informed consent: do HIV-positive physicians have a duty to disclose their status
      to their patients?

PMID- 11594196
TI  - Assessing HIPAA's implications for medical industry lockbox operations.

PMID- 11594197
TI  - IRS Revenue Procedure 97-13 regarding tax-exempt bond financing recently revised.

PMID- 11594198
TI  - Stark: the key exceptions for group practices.

PMID- 11594199
TI  - A show of handhelds.

PMID- 11594200
TI  - Putting your assets to work.

PMID- 11594201
TI  - The survey says.

PMID- 11594202
TI  - Radiology goes filmless.
AB  - PROBLEM: Long turnaround time for radiology reports, unacceptable percentage of
      misplaced films. SOLUTION: Installation of hospitalwide PACS, implementation of
      voice recognition dictation system, upgrade of RIS. RESULTS: Rapid and
      significant improvement in reporting times, virtual elimination of misplaced
      films, integration of radiology services throughout the enterprise. KEYS TO
      SUCCESS: Detailed financial model and needs assessment, commitment by management
      and staff, well-planned implementation, choice of vendor that provides total
      solution and support.

PMID- 11594203
TI  - The unsinkable ASP.

PMID- 11594204
TI  - Healthcare from a new perspective.

PMID- 11594206
TI  - An electronic health record for the real world.

PMID- 11594205
TI  - Computer-based patient record systems.

PMID- 11594207
TI  - Inpatient e-ordering.

PMID- 11594208
TI  - Technology takes on heart disease.

PMID- 11594209
TI  - [15 years experience with the ileal neobladder. What have we learned?].
AB  - During the past 15 years, orthotopic bladder reconstruction has evolved from
      experimental surgery over "standard of care at larger medical centers" to become
      the preferred method of urinary diversion in both sexes. The paradigm for
      choosing a urinary diversion has changed substantially over that time. In 2001,
      all cystectomy patients are candidates for a neobladder, and we should identify
      those patients in whom orthotopic reconstruction may be less ideal, noting that
      the percentage of patients receiving a neobladder today averages 60 to 70
      percent. Relative contraindications and comorbidity now play a smaller role in
      choosing the neobladder option. Patient selection criteria include both patient
      factors and cancer factors. The primary patient factor being the patient's desire
      for a neobladder. The psychologically damaging stigma to the patient who enters
      surgery expecting a neobladder but awakens with a stoma now plays an increasing
      role. Nevertheless, there are patients who are better served with a conduit.
      Among that are patients whose main motivation is to "get out of the hospital as
      soon as possible", and patients who will be happy to resume a normal, relatively
      sedentary life and who have no concerns about body image. Two important criteria
      that must be maintained when contemplating a neobladder procedure--the urethral
      sphincter must remain intact and the cancer operation must not be compromised.
      However, increasing experience has forced less restrictiveness as far as tumor
      stage is concerned. A recent study of 435 bladder cancer patients who had bladder
      replacements after cystectomy, experienced a local recurrence rate of 10 percent.
      Interference of the local recurrence with the neobladder occurred in just 11
      patients--infiltration in six, and obstruction in five. Survival was limited
      despite multimodality therapy. The option of a neobladder reduced the physician
      and patient reluctance to perform cystectomy early in the disease process,
      thereby increasing the survival rate, and patients can anticipate normal
      neobladder function until time of death. It can be concluded that a neobladder
      for locally advanced cancer and positive nodes is no more problematic than a
      conduit. The structural and ultrastructural changes which occur in neobladder
      mucosa are biphasic. The early phase is inflammatory, showing an infiltration of
      the lamina propria and a reduction in microvilli. After one year the late
      regressive phase starts, ending up in a flat mucosa and a stratified epithelium.
      The structure and response of the implanted ileum change to a detrusor-type:
      response. The structural and ultrastructural changes an ileal mucosa lead to a
      primitive surface and glandular epithelium similar to urothelium. This
      transformation of the ileal mucosa minimizes the risk of metabolic complications.
      We conclude that mother nature engineers a new bladder almost as good as the one
      given by God initially. The risk of obstruction of non refluxing techniques is at
      least twice that following a direct anastomosis. There is no longer a
      justification of any antireflux mechanism. Ileum seems to be clearly superial to
      colon when continence rates, metabolic safety and surgeons's issues are
      considered.

PMID- 11594210
TI  - [Reconstruction of the lower urinary tract. Developments at the beginning of a
      new century].
AB  - Gastrointestinal segments are currently by far the most popular method to create
      a bladder substitute. Attempts have been made to further reduce the morbidity and
      burden for patients by using minimal invasive techniques for both cystectomy and
      urinary diversion. However, laparoscopy for acceptable forms of urinary diversion
      is time consuming and costly. A neobladder "off the shelf" would be a better
      solution. Tissue engineering is an exciting new field which enables the
      cultivation and expansion of individual bladder cells obtained by transurethral
      biopsy, the attachment of these cells to a support matrix, and their
      reimplantation into the body. Advances both in biomaterials as well as in the
      cultivation and expansion of bladder cells are described. Promising routine
      clinical applications of tissue engineering may still need several years. Free
      neurovascular muscle transfer to the bladder demonstrated both experimentally and
      clinically to be a suitable treatment modality in patients with bladder
      acontractility. This may therefore be the next logical step towards an improved
      bladder substitute by combining well vascularized flaps with urothelial cell
      seeding. Thus a combination of commonly used flap techniques and tissue
      engineering may soon be possible.

PMID- 11594211
TI  - [Radiotherapy of urothelial carcinomas of the urinary bladder].
AB  - Radiotherapy of bladder cancer is a locally effective therapeutic approach. It is
      increasingly becoming part of the multimodal protocols aimed at the preservation
      of both organ and organ function. In this context, it is an alternative to
      cystectomy. The addition of chemotherapy to radiotherapy enhances the curative
      potential of this non-surgical approach and may be useful especially in older,
      multimorbid patients. If chemotherapy can not be applied, the use of radiotherapy
      alone is reasonable, although in advanced tumors the results are disappointing.
      After the transurethral resection of bladder cancer, postoperative radiotherapy
      should be considered in muscle-invasive cancer as well as when other negative
      prognostic factors occur. The prerequisites for an effective, minimally toxic,
      state of the art radiotherapy are a subtle treatment-planning procedure and an
      accurate delivery of the radiation.

PMID- 11594212
TI  - [Radiochemotherapy of urothelial carcinoma].
AB  - Radical cystectomy is the current standard therapy for muscle invasive or locally
      advanced transitional cell carcinoma of the bladder. Organ-preserving
      monotherapeutic alternatives (e.g. transurethral resection, radiotherapy) do not
      lead to similar cure rates. In selected cases, a trimodal approach using
      transurethral resection and combined radio- and chemotherapy can be as efficient
      as cystectomy.

PMID- 11594213
TI  - [Leiomyoma of the kidney. Differential diagnostic aspects of renal cell carcinoma
      with increasing clinical relevance].
AB  - Renal leiomyoma is a rare benign tumor which has its origin in smooth muscle
      cells of different structures of the kidney. The clinical incidence of renal
      leiomyoma is much lower than the frequency described in large autopsy studies.
      Renal leiomyomas are mainly located in the renal capsula and pelvis or next to
      those structures. Clinical symptoms are nonspecific (e.g., flank pain or flank
      tumor) or completely absent, making most of the leiomyomas an incidental finding
      during routine diagnostics. A differential diagnosis between renal leiomyoma and
      renal cell carcinoma on the basis of medical imaging is extremely difficult.
      Therefore, laparotomy and nephrectomy are performed in most cases of suspected
      renal cell carcinoma. The definitive diagnosis of a leiomyoma is only possible
      after histological examination of the tumor. Due to the rising number of
      diagnoses resulting from improved medical imaging, renal leiomyomas are gaining
      more importance in the differential diagnosis of renal cell carcinoma, especially
      with respect to kidney-sparing surgery.

PMID- 11594214
TI  - [Unenhanced spiral computerized tomography in acute diagnosis of flank pain.
      Examination in contraindications for contrast medium administration].
AB  - The diagnostic value of unenhanced helical computed tomography was investigated
      in a prospective study. In 53 patients (aged 35 to 82 years) with acute flank
      pain tomography was performed in addition to abdominal plain film and ultrasound
      examination. All 53 patients had a contraindication for intravenous
      administration of contrast medium. Ureteral calculi were either confirmed or
      excluded by retrograde ureteropyelography in 44 cases, in 9 patients by
      asservation of calculi and clinical follow-up. Helical computed tomography was
      able to precisely identify all of the 34 ureteral calculi, whereas abdominal
      plain films led to 6 false positive and 17 false negative findings. In 1 patient
      with retroperitoneal lymphoma (diagnosed by CT) false positive findings occurred.
      Unenhanced helical computed tomography reaches a distinctively increased
      diagnostic value (sensitivity 100%, specificity 95%, accuracy 97%) in the
      evaluation of acute flank pain as compared to conventional radiologic imaging and
      ultrasound. This non-invasive procedure is to be considered method of choice for
      patients with contraindications for the application of radiopaque material.

PMID- 11594216
TI  - [Kidney Transplantation Study Circle of the German Urology Society Graduate and
      Continuing Education Committee. Report of the annual meeting, 12-14 October 2000,
      Rostock].

PMID- 11594215
TI  - [Dermatography. An effective method for pacemaker marking after spinal cord
      injuries and implantation of a Brindley stimulator for neurogenic bladder].
AB  - In our department, two spinal cord lesion patients suffering from neurogenic
      bladder dysfunction were selected for the implantation of a Brindley stimulator,
      as they could not be managed by conservative treatment. Accurate positioning of
      the external transmitter block over the subcutaneous receiver block, which is
      essential for the Brindley stimulator to function correctly, posed problems for
      the relatives who had to apply the external transmitter. In order to facilitate
      positioning, dermatography was used to mark the exact spot where the external
      transmitter should be placed. A 3-year follow-up showed that this marking solved
      the problem completely and that recurrent urinary tract infections stopped.

PMID- 11594217
TI  - [Use of BCG in superficial urinary bladder carcinoma].

PMID- 11594218
TI  - [New methods for reconstruction of the ocular surface].

PMID- 11594219
TI  - [Amniotic membrane transplantation for reconstruction of the ocular surface].
AB  - Amniotic membrane transplantation has been recently gained wide-spread attention
      as a new method for reconstruction of the ocular surface. However long term
      prognosis of the surgical intervention as well as action mechanism are poorly
      defined. Therefore, we review the current literature concerning the application
      of amniotic membrane in ophthalmology and the outcome of the surgery. Amniotic
      membrane is used as graft or patch to promote epithelial healing of persistent
      epithelial defects, corneal ulcers and following penetrating keratoplasty. It is
      also used to seal corneal perforations and to treat bullous keratopathy. Amniotic
      membrane patches facilitate epithelial healing and reduce the number of
      complications after chemical burns. For partial limbal deficiency, amniotic
      membrane alone can be sufficient, while total limbal deficiency requires
      combination with stem-cell transplantation. Furthermore amniotic membrane grafts
      restore conjunctival surfaces following removal of lesions such as pterygium,
      tumor, scar, symblepharon, and conjunctivochalasis. The prognosis of amniotic
      membrane transplantation depends on the underlying disease and the quality of the
      ocular surface and is inversely related to the degree of inflammation. Recent
      investigations of the action mechanisms describe intrinsic antiinflammatory
      properties of the amniotic membrane.

PMID- 11594220
TI  - [Ex-vivo expansion of cornea stem cells. Experimental principles and initial
      clinical results].
AB  - The ocular surface epithelium is composed of conjunctiva, limbus and cornea.
      These three compartments and an stable preocular tear film are crucial factors
      determining ocular surface health. Stem cells of the corneal epithelium are
      exclusively located at the limbus. Limbal stem cells are the ultimate source of
      regeneration of the entire corneal epithelium and in a variety of ocular surface
      diseases limbal stem cell deficiency has been observed to be a characteristic
      feature. Therefore renewal of the limbal stem cell population using different
      surgical techniques has been described as the only possible therapeutic strategy.
      Recent advancements in cell biology have enabled the development of new models of
      tissue engineering as a tool for tissue replacement. The aim of this review is to
      summarize recently reported clinical and experimental studies showing new
      developments in tissue engineering for the reconstitution of the ocular surface
      epithelium.

PMID- 11594221
TI  - [Limbus transplantation for reconstruction of the ocular surface].
AB  - Proliferation of the corneal epithelium originates in undifferentiated, long
      lived stem cells that are located in the basal limbal epithelium. Stem cells are
      important for corneal epithelial regeneration and wound healing. Depletion of
      stem cells due to accidents as well as malfunctions of stem cells due to inborn
      or inflammatory diseases result in limbal stem cell deficiency. Limbal deficiency
      is characterized by conjunctivalization of the cornea with vascularization and
      opacification. Partial limbal deficiency can be treated by removing ingrown
      conjunctival epithelium thus allowing normal limbal epithelium to repopulate the
      cornea. Unilateral limbus-derived stem cell disease requires either limbal
      autograft transplantation from the healthy partner eye or kerato-limbal allograft
      transplantation. Several modifications of the latter technique have been
      performed including large kerato-limbal lamellar grafts and central penetrating
      kerato-limbal allografts. All homologous procedures render a very high risk of
      immunological reactions that require long term systemic immunosuppression. The
      use of amniotic membrane, better pharmacological drugs for immunosuppression and
      improvements in the HLA-matching of limbal allografts as well as ex vivo
      expansion of corneal stem cells should allow for better reconstruction of the
      ocular surface in limbal deficiency.

PMID- 11594223
TI  - [The optics of retinal blood vessels and their significance for scanning laser
      Doppler flowmetry].
AB  - Recently, the scanning laser Doppler flowmetry (SLDF) has been developed as a
      standard method for the quantification of retinal blood flow. However, the
      measured quantities flow, volume, and velocity depend on the angle between the
      direction of the blood flow and of the light. The underlying theory assumes
      isotropic illumination of the vessel. This assumption, however, is not valid for
      light back-scattered from retinal vessels. This paper investigates the
      contribution of different pathways of the light to the SLDF signal by a Monte
      Carlo simulation. It is shown that the light measured on a vessel having a
      thickness of 50 microns is predominantly back-scattered from the blood inside the
      vessel, whereas the measurement on vessels 20 microns in diameter or less also
      includes light transmitted through the vessel.

PMID- 11594222
TI  - [Quantification of retinal nerve fiber thickness. A comparison of laser scanning
      ophthalmoscopy, polarimetry and optical coherence tomography in healthy and
      glaucomatous eyes].
AB  - PURPOSE: To evaluate the thickness of the retinal nerve fiber layer (RNFL) in
      healthy eyes and in eyes of patients with primary open angle glaucoma using the
      Heidelberg retina tomograph (HRT), the nerve fibre analyser (NFA) and the optical
      coherence tomograph (OCT). METHODS: In this prospective cohort study, 40 normal
      eyes and 86 eyes of age-matched glaucoma patients were compared by confocal
      scanning laser tomography using the HRT, scanning laser polarimetry (NFA) and
      optical coherence tomography (OCT). The RNFL thickness was measured in the
      superior, inferior, nasal and temporal regions as well as the total
      circumference. RESULTS: All three methods revealed a statistically significant
      difference between normal and glaucomatous eyes with respect to the mean RNFL
      thickness in the inferior and superior regions (p < 0.001). The mean RNFL
      thickness in the superior region was 329 microns (HRT), 87 microns (NFA) and 94
      microns (OCT) in healthy volunteers compared to 275 microns (HRT), 72 microns
      (NFA) and 82 microns (OCT) in the patient group. In the inferior region, it was
      323 microns (HRT), 87 microns (NFA) and 93 microns (OCT) in healthy subjects
      versus 240 microns (HRT), 74 microns (NFA) and 83 microns (OCT) in glaucoma
      patients. Cut-off points to differentiate between normal and glaucomatous eyes
      could not be defined. There was no difference in the RNFL thickness of right and
      left eyes. CONCLUSIONS: In RNFL thickness measurements using HRT, NFA and OCT,
      glaucoma patients showed a significantly thinner RNFL in the superior and
      inferior areas compared to healthy volunteers. These results confirm the known
      histological and fundus photographic findings of RNFL thinning near the optic
      disc in glaucoma patients. Although RNFL thickness cannot be used to diagnose
      glaucoma in individual patients due to the high interindividual differences, the
      quantitative assessment of RNFL thickness may complement the diagnostic
      armamentarium as a sensitive parameter for diagnosing and monitoring glaucomas.

PMID- 11594224
TI  - [Biomorphometry of corneal epithelium with slit lamp-adapted optical coherence
      tomography].
AB  - INTRODUCTION: The purpose of this study was to evaluate the biomorphometry of the
      corneal epithelium with slitlamp-adapted optical coherence tomography (OCT).
      PATIENTS AND METHODS: In a clinical study, slitlamp-adapted OCT of the cornea was
      performed in 15 patients before and immediately after therapeutic corneal
      abrasion. Central corneal epithelium thickness measurements were compared to the
      pre- and postoperative central corneal thickness. RESULTS: Preoperatively, the
      corneal epithelium could be visualised from the highest OCT light reflections at
      the interfaces air-tear film and epithelium-Bowman's membrane. The preoperative
      mean geometrical central epithelial thickness determined with OCT ranged from 65
      +/- 12 microns to 72 +/- 14 microns (45-92 microns). The mean difference of the
      pre- and postoperative central corneal thickness was 48 +/- 19 microns (9-79
      microns). This resulted in a deviation from the direct epithelial thickness
      measurements of 26-33%. The reproducibility of the geometrical epithelial
      thickness was +/- 9 microns. CONCLUSIONS: Slitlamp-adapted OCT enabled a
      noncontact evaluation of the corneal epithelium. The difference between direct
      and indirect corneal epithelium thickness measurements could be related to the
      partial optical inclusion of the precorneal tear film and the Bowman's membrane.
      With some restrictions the biomorphometry of the corneal epithelium with slitlamp
      adapted OCT seems to be a valuable technique to monitor therapeutical and
      refractive procedures of the cornea.

PMID- 11594225
TI  - [Development of an organotypic corneal construction as an in vitro model for
      permeability studies].
AB  - BACKGROUND: In vitro investigations of transcorneal permeation behaviour with new
      drugs in ophthalmology are mainly carried out using excised corneas taken from
      slaughtered or experimental animals. Analogous to previously used dermis models,
      an in vitro model was constructed from porcine corneal cell cultures and the
      permeation barrier properties were tested and compared with permeation data from
      excised corneas. METHODS: Epithelial, stroma and endothelial cells were
      successfully isolated by treatment with various enzymes and a corneal equivalent
      was created step-by-step which morphologically resembled the original tissue.
      Five different drug formulations were investigated and pilocarpine hydrochloride
      was chosen as the model drug. The permeation studies were made with a modified
      Franz cell and analysis was performed by high performance liquid chromatography.
      Permeation data from excised corneas and from the cornea construct were compared
      whereby data obtained with lipophilic preparations did not differ (factor of 1)
      and those obtained with aqueous formulations were relatively similar (factor of 3
      4). RESULTS AND CONCLUSIONS: The results obtained show that the cornea construct
      can be used as an alternative to excised corneas for in vitro investigations of
      ophthalmic drug preparations.

PMID- 11594226
TI  - [Better evaluation of HRT (Heidelberg Retina Tomography) images by 3-dimensional
      display].
AB  - BACKGROUND: The Heidelberg retina tomograph (HRT) is routinely used for the
      analysis of the structures of the eye ground (glaucoma diagnosis). The Dresden 3D
      display, developed by the Technical University Dresden, is an autostereoscopic
      display which facilitates the three-dimensional presentation of geometrical data.
      The aim of this study was to test whether the spatial presentation improves the
      precision of measurements. METHODS: Out of the patients who attended our hospital
      for glaucoma treatment within the past 3 years, 17 (9 women and 8 men) were
      chosen on grounds of a long follow-up time. In addition the patients had to have
      had at least 4 HRT examinations (mean: 5.29). The patients data was explored in
      three ways: 1. regular HRT examination, 2. manual follow-up HRT examination and
      3. examination with the Dresden 3D-display. RESULTS AND CONCLUSIONS: The
      measurements performed with the Dresden 3D-display showed a significantly higher
      precision compared to traditional HRT measurements. With spatial presentation a
      better assessment of the measured HRT data is possible.

PMID- 11594227
TI  - [Should indications for amniotic membrane transplantation be altered in
      concurrent rheumatoid polyarthritis?].
AB  - BACKGROUND: Amniotic membrane transplantation (AMT) shows good results in corneal
      epithelial defects or ulcerations. However, in patients with rheumatoid arthritis
      (RA) these corneal defects represent a somewhat greater challenge. We address the
      question whether AMT has to be indicated differently in RA patients. PATIENTS AND
      METHODS: We retrospectively analysed 25 AMTs performed between October 1998 and
      August 2000 in 22 patients for corneal epithelial defects and ulcerations. In 8
      patients (11 AMTs) RA was present (group A) and no RA (group B) was found in 14
      patients (14 AMTs). RESULTS: Epithelial closure could be achieved in 24/25 cases
      after a mean of 24.9 days. In 15/25 cases the epithelium remained closed over a
      minimum of 3 months (successful AMT). In group B, 12/14 AMTs (85.7%) were
      successful, but only 3/11 AMTs (27.3%) were successful in group A. DISCUSSION: In
      addition to the pronounced keratoconjunctivitis sicca, immune-mediated
      inflammatory aspects are suspected to be the reason for the poor results of AMT
      in RA patients. But as alternative surgical procedures (e.g. keratoplasty)
      implicate specific problems in RA, we believe that after failure of conservative
      treatment AMT is a reasonable procedure for corneal defects even in RA patients.

PMID- 11594228
TI  - [Gernet and GOW-70-Program intraocular lens calculation. Significance of the of
      the position of the principal plane of the lens in phakic and pseudophakic eyes
      for accuracy of the target refraction of different IOL types].
AB  - The GOW 70 PC programme utilises the individual bio-anatomy of the phacic
      cataract eye in the IOL power calculation for multifocal or monofocal in-the-bag
      implantation for all common IOL types. In addition, an aniseiconia evaluation
      programme is included. The Gernet IOL power calculation is based on the GOW 70,
      71 formulae which consists of the PC programme (one disc), one table (the 60%
      rule), an instruction for use in personal computers (Windows, Word) and in the
      60% procedure. This is based on ultrasound immersion measurements of about 20,000
      phacic eyes with and without cataracts and after 2,000 IOL implantations by
      various surgeons using the d-values of the human eye lenses of the cataract eye
      and the d-values of the IOL types used. The d-value of a phacic eye is the
      distance between the corneal vertex and the principal plane (infinitely thin
      lenses) of the human eye lens and is formed from the depth of the anterior
      segment (cornea + AC) + 60% of the human lens thickness. The d-value of a
      pseudophacic eye is the distance between the corneal vertex and the principal
      plane of the chosen IOL type. In 1984, the first definite clinical connection
      between the d-values of human eye lenses and of implanted PC IOL (6.0 mm-1.5 mm =
      4.5 mm) was established. In 1992 and 1998 it was extended to the "newer" 60% rule
      and to the 60% procedure, respectively.

PMID- 11594229
TI  - [Palliative treatment of deep penetrating tumors in the medial eyelid eyelid with
      carbon dioxide laser].
AB  - A deep penetrating tumor was removed from the medial lid angle with a carbon
      dioxide laser knife for palliative reasons. After an early recurrence, which was
      also removed with the laser knife, we observed a satisfactory healing per
      secundam intentionem. After carbon dioxide laser excision no plastic covering is
      necessary. This quick and easy method is especially advantageous for patients
      with a bad compliance.

PMID- 11594230
TI  - [Ablation surgery. From the inside, from the outside, or both?].

PMID- 11594231
TI  - [Is scleral buckling still current?].
AB  - We report a survey among German-speaking vitreo-retinal surgeons, considering
      their decisive factors and preferred surgical techniques in simple and
      complicated rhegmatogenous situations. In cases of simple retinal detachment
      conventional buckling surgery is the favoured surgical approach. Minimal-invasive
      techniques like the balloon operation or pneumatic retinopexy are chosen by less
      than 5% of the surgeons. For more complicated retinal detachments a strong trend
      towards primary vitrectomy becomes apparent. In difficult rhegmatogenous
      situations which are still treatable with conventional buckling procedures, 45%
      of surgeons prefer a primary vitrectomy and only 55% chose scleral buckel or
      encircling band procedures.

PMID- 11594232
TI  - [Scleral buckling versus primary pars plana vitrectomy in relation to pathology
      of the vitreous body].

PMID- 11594233
TI  - [Conventional ablation surgery or primary vitrectomy in complicated retinal
      holes].
AB  - BACKGROUND: We retrospectively evaluated 100 difficult cases out of 803
      consecutive eyes with retinal detachment in order to determine the best surgical
      procedure in cases with difficult break configurations such as multiple, large,
      and central holes. METHODS: We treated the eyes either with conventional buckling
      surgery (n = 60) encircling buckle (EB) plus sponge exoplant (SP) (n = 45) or
      multiple sponge exoplants (n = 15) or with primary vitrectomy (PV) (n = 40). From
      the 40 patients in the PV group, 10 underwent vitrectomy plus intraocular gas
      only, in the other cases an encircling band was used (n = 30). RESULTS: In the
      EB/SP group the retina was attached directly after surgery in 59/60 cases. During
      a mean follow-up of 14.5 months redetachment occurred in 4/60 cases. In the PV
      group the retina was attached in 37/40 cases after resorption of gas and during
      the mean follow-up of 9.3 months redetachment occurred in an additional 4/40
      cases. Complications during surgery in the EB/SP group were retinal incarceration
      (n = 2) and subretinal hemorrhage (n = 2). In the PV group intraoperative
      complications included choroidal detachment (n = 1) and iatrogenic holes (15%).
      Postoperative complications were choroidal detachment in 6/60 vs 0/40, transitory
      increased intraocular pressure (30% vs 68%). Double vision, however correctable
      by means of prisms, occurred in 4/60 vs 0/40. CONCLUSIONS: The primary attachment
      rate is high and similar with both procedures. The spectrum of intra- and
      postoperative complications is however different between both groups.

PMID- 11594234
TI  - [Phacoemulsification and vitrectomy with the erbium:YAG laser and
      phacoemulsification with the neodymium:YAG laser].
AB  - There are an increasing number of possible applications for the use of Erbium:YAG
      and Neodymium:YAG lasers in ophthalmology. Laser-phacoemulsification as well as
      Erbium-laser vitrectomy is of major interest. We report on the underlying
      technology and more than 1-year-experience using the PHACOLASE (Asclepion
      Meditec, Jena, Germany, 10-100 Hz frequency, 5-50 mJ single pulse energy) for
      phacoemulsification and pars plana vitrectomy and the Lyla-Dodick laser
      photolysis (A.R.C. Laser, Eckental-Forth, Germany, 1-20 Hz, up to 8 mJ single
      pulse energy). The Erbium:YAG-laser as well as the Neodymium:YAG-laser enabled us
      to extract lenses with up to medium hard nuclei. Moreover, the Erbium laser
      enabled fast vitrectomy with little mechanical traction. In many of our initial
      surgical operations we had to change to mechanical vitrectomy due to initial
      technical problems. No new complications occurred intra- or postoperatively. The
      handpiece worked well in removing vitreous bodies, but was not feasible for
      cutting membranes. Modified handpieces for this purpose are under development.

PMID- 11594235
TI  - [Application of diagnosis related groups (DRGs) in ophthalmology in Germany].
AB  - Starting on 01.01.2003 the hospital reimbursement system in Germany will be
      transferred completely to a diagnosis-related groups (DRG) system based on the
      data of 2001. As the reimbursement system is of vital importance for the
      development of a speciality, current information is given about the impact of the
      new payment system on ophthalmology. The Australian AR-DRG system to be adopted
      in Germany distinguishes 20 DRGs for ophthalmology. The patients are grouped into
      the DRGs according to their principal diagnoses and comorbidities and the
      procedures coded by electronic data processing. Errors in coding and missing data
      may cause reductions in the hospital budget as do economically inhomogeneous
      DRGs. The tight timetable given by the legislation requires completion of
      determining DRG groups and weightings by 31.12.2001. However, important
      prerequisites such as the mapping tables of the Australian DRGs are still
      missing, which means that hospitals have to prepare for the new system like a
      pilot flying blind with no instruments.

PMID- 11594236
TI  - [Stab injury of the orbit].

PMID- 11594237
TI  - [Diabetic maculopathy. Etiological mechanisms and possible treatment approaches].

PMID- 11594238
TI  - Comparison of rheumatoid arthritis care costs in patients starting therapy with
      leflunomide versus etanercept.
AB  - OBJECTIVE: To identify differences in rheumatoid arthritis (RA) care costs and
      utilization among patients receiving therapy with leflunomide (LEF) or etanercept
      (ETA). STUDY DESIGN: A retrospective cohort analysis of patients diagnosed with
      RA and starting treatment with LEF or ETA. METHODS: Patients diagnosed with RA
      and receiving newly prescribed LEF or ETA in 1998 were identified from a database
      containing patient-level medical and pharmaceutical claims. Patients were
      subsequently observed for 6 months. RA-related treatment charges during the
      observation period were compared between cohorts. RESULTS: A total of 527 LEF-
      and 281 ETA-treated patients were identified. The 2 cohorts were comparable with
      respect to demographics, comorbid conditions, and concomitant medication use,
      although LEF recipients were, on average, older than ETA recipients (mean age
      52.97 versus 48.43 years; P < .0001). ETA recipients had higher mean 6-month
      postdiagnosis charges than LEF recipients ($7722.01 +/- $5285.20 versus $3301.84
      +/- $4054.75; P < .0001). This difference was primarily related to differences in
      RA-related pharmacy charges ($5877.78 +/- $2237.68 versus $1877.23 +/- $1258.05;
      P < .0001). CONCLUSIONS: Compared with charges in the ETA group, RA care costs in
      the LEF group were significantly lower during the 6 months after the initiation
      of therapy. The difference in mean total RA-related charges was attributable
      mainly to the difference in RA-related pharmacy charges.

PMID- 11594239
TI  - Pioglitazone: mechanism of action.
AB  - Thiazolidinediones, such as pioglitazone, are synthetic ligands for peroxisome
      proliferator-activated receptors (PPARs). They alter the transcription of genes
      influencing carbohydrate and lipid metabolism, resulting in changed amounts of
      protein synthesis and, therefore, metabolic changes. Pioglitazone improves
      glycaemic control in people with Type 2 diabetes by improving insulin sensitivity
      through its action at PPAR gamma 1 and PPAR gamma 2, and affects lipid metabolism
      through action at PPAR alpha. The results of these interactions include increases
      in glucose transporters 1 and 4, lowered free fatty acids, enhanced insulin
      signalling, reduced tumour necrosis factor alpha (TNF alpha) and remodelling of
      adipose tissue. Together, these can increase glucose uptake and utilisation in
      the peripheral organs and decrease gluconeogenesis in the liver, thereby reducing
      insulin resistance.

PMID- 11594240
TI  - Pharmacokinetics and clinical efficacy of pioglitazone.
AB  - Pioglitazone is a thiazolidinedione that increases insulin sensitivity in target
      tissues. It is well-absorbed, with a mean absolute bioavailability of 83% and
      reaching maximum concentrations in around 1.5 hours. It is metabolised by the
      hepatic cytochrome P450 enzyme system. However, unlike troglitazone, studies have
      provided no evidence to suggest that pioglitazone administration leads to
      inhibition or induction of any of the P450 isoenzymes involved in drug
      metabolism. Therefore pioglitazone may have lower potential for drug interaction.
      The half-life is about 9 hours but two active metabolites mainly contribute to
      the extended glucose-lowering effects. It is administered once daily without
      regard to meals. The pharmacokinetics are not significantly altered in Type 2
      diabetes, renal or hepatic insufficiency or in the elderly. In placebo-controlled
      clinical studies, pioglitazone effectively improved glycaemic control in people
      with Type 2 diabetes as evidenced by significant reductions in HbA1c and fasting
      plasma glucose, whether used as monotherapy or in combination with sulphonylurea,
      metformin or insulin. Pioglitazone also had a beneficial effect on the abnormal
      lipid profile seen in Type 2 diabetes. Compared with placebo, pioglitazone
      significantly reduced serum triglycerides and increased high density lipoprotein
      cholesterol with no change in low density lipoprotein or total cholesterol.

PMID- 11594241
TI  - Safety profile of pioglitazone.
AB  - The safety profile of pioglitazone has been evaluated in trials including over
      5,400 subjects, of whom over 3,500 received active treatment resulting in over
      2,500 patient-years of exposure. Since its launch, over 1.4 million patients have
      been prescribed pioglitazone. This paper will examine the clinical trial
      tolerability and safety data available for pioglitazone. Safety was evaluated
      both as monotherapy and in combination with other antihyperglycaemic drugs. All
      studies had a placebo-controlled, double-blind, randomised, parallel-group, multi
      centre design, in which pioglitazone was administered once daily over a period of
      16-24 weeks. Most trials also had a long-term open label extension. In these
      trials, adverse events were recorded, as were details of laboratory blood values,
      urine analysis, vital signs and electrocardiograms. In addition, specific studies
      were conducted to examine any effects of pioglitazone on cardiac structure and
      function, and body composition. This paper will also briefly review data
      available from post-marketing surveillance.

PMID- 11594242
TI  - New advances in the management of insulin resistance in type 2 diabetes.
      Introduction.

PMID- 11594243
TI  - The reality of type 2 diabetes treatment today.
AB  - The 5-year targets set by the St Vincent Declaration for cardiovascular events
      and other diabetes outcomes have still not been met, despite concerted efforts to
      treat cardiovascular risk factors in this population. Since St. Vincent we have
      seen a new focus on the care of Type 2 diabetes towards multiple risk factor
      reduction, including blood pressure, lipids, smoking and glycaemic control. The
      other new concept is that insulin resistance is a key abnormality in the
      pathogenesis of Type 2 diabetes. The thiazolidinediones are a new class of drug
      that ameliorate insulin resistance, and we await to see if their use is
      associated with improved diabetes outcomes. The third key issue is that modern
      day diabetes care requires polypharmacy. However, adding several drugs to the
      list of medications taken by many patients with Type 2 diabetes may bring
      problems of compliance. A typical patient might be taking several tablets for
      diabetes, plus medications to address cardiovascular risk factors/disease and
      typical co-morbidities of an ageing population. There is evidence that adherence
      to therapy is a major issue in diabetes care. More research is needed to define
      ways of improving adherence [corrected].

PMID- 11594244
TI  - Pioglitazone: the future.

PMID- 11594245
TI  - Epidemiology of cardiovascular disease in type 2 diabetes.
AB  - Cardiovascular complications are a major cause of morbidity and mortality in Type
      2 diabetes. Diabetes patients have a higher risk of developing cardiovascular
      disease and a poorer outcome from cardiovascular events than do patients without
      diabetes. Although part of this increased risk may be related to glycaemic
      control, other factors are also involved. Several of the known cardiovascular
      risk factors are increased in patients with Type 2 diabetes, including
      hyperinsulinaemia, hypertension, dyslipidaemia (decreased high density
      lipoprotein cholesterol levels and increased plasma triglycerides and a
      preponderance of small, dense low density lipoprotein particles) and abdominal
      obesity. All these changes appear to be related to insulin resistance, which is a
      key feature of Type 2 diabetes. Addressing cardiovascular risk factors,
      particularly insulin resistance, therefore, should be an equally important part
      of the management of Type 2 diabetes as glycaemic control.

PMID- 11594247
TI  - Statins in acute coronary syndromes: from bench to bedside.

PMID- 11594246
TI  - Insulin resistance and its impact on the approach to therapy of type 2 diabetes.
AB  - Insulin resistance is a core defect in Type 2 diabetes, occurring in peripheral
      organs (skeletal muscle and adipose tissue) leading to decreased glucose uptake
      and utilisation and in liver leading to increased hepatic glucose production. As
      long as the beta-cell can compensate for this by producing more insulin, glucose
      tolerance remains normal. However, as insulin resistance worsens, the beta-cell
      starts to fail to compensate leading to impaired glucose tolerance and then frank
      diabetes. The exact pathophysiology of insulin resistance is not clear but it
      probably involves a combination of genetic and environmental factors. These
      factors may result in changes in the number of insulin receptors, their affinity
      for insulin or a defect in post-receptor signalling or a combination of these.
      Insulin resistance also affects lipid metabolism such that there is increased
      production of triglycerides from the liver, which in turn both amplifies insulin
      resistance and exacerbates atherogenesis. The promotion of atherosclerosis by
      insulin resistance means that patients with Type 2 diabetes are at particularly
      high risk of cardiovascular disease. Therefore, treatment of insulin resistance
      with thiazolidinediones has the potential to offer improvements both in glycaemic
      control and in cardiovascular events.

PMID- 11594248
TI  - Lungs of gold: the global initiative for chronic obstructive lung disease (GOLD).

PMID- 11594249
TI  - Follow-up of breast cancer: time for a new approach?
AB  - After treatment for breast cancer women are monitored for recurrent disease by
      means of routine hospital-based follow-up appointments. The aim of this study is
      to determine the efficiency of this system, by establishing how recurrence
      presents to our hospital. The study comes at a time of increasing pressure on
      breast clinics from new patient referrals and the need, since April 1999, to see
      all cases classified as urgent within two weeks of referral. A consecutive series
      of 643 patients who presented with operable breast cancer between 1992 and 1998
      were reviewed. Details about the 108 patients who had locoregional or metastatic
      relapse were obtained from our breast cancer database and their clinical records.
      Full data were available on 104 patients: 77 (74%) were seen at expedited
      (interval) appointments and a further 18 (17.3%) drew attention to symptoms at a
      routine visit. Two cases of locoregional recurrence were revealed by surveillance
      imaging. Unsuspected disease, locoregional in all cases, was detected on
      examination in 7 (6.7%) patients. The median time to presentation of recurrence
      was 19 months for metastatic and 18 months for locoregional disease. Breast
      cancer recurrence usually presents to an interval clinic. Most cases that are
      confirmed following a routine review are already symptomatic. Long-term routine
      hospital follow-up after treatment for breast cancer appears inefficient and
      unnecessary. Following liaison with local general practitioners we propose to
      discharge patients from routine review after two years. Thereafter they will have
      scheduled appointments with their GPs with immediate access to specialist review
      in the breast care unit if required.

PMID- 11594250
TI  - Similar frequency of TT virus infection in patients with liver enzyme elevations
      and healthy subjects.
AB  - TT virus (TTV) is a novel DNA virus that has been identified in patients with
      post-transfusional hepatitis of unknown aetiology. However, its pathogenic role
      in liver injury remains unclear. To determine its frequency and clinical impact
      in cryptogenic liver diseases, we investigated the TTV prevalence in patients
      with liver enzyme elevations of unknown aetiology and in healthy subjects. Fifty
      four patients (33 male, 21 female) who have been followed up for elevated ALT/AST
      levels of unknown aetiology and 118 healthy subjects (99 male and 19 female) were
      included in the study. TTV DNA was investigated by the polymerase chain reaction.
      Other possible causes of transaminase elevation were excluded in detailed
      biochemical and serological tests. A liver biopsy was performed in 45 patients.
      TTV DNA was detected in 46 patients with liver enzyme elevations (85.1%) and in
      94 healthy subjects (79.6%). There was no statistical difference between the
      groups (p = 0.51). Histological examination of the liver revealed no specific
      change in TTV DNA positive patients that could be attributed to this virus
      infection. These results showed that TTV is a common virus in patients with liver
      enzyme elevation of unknown aetiology and even among healthy subjects in our
      geographical area. TTV infection is therefore widespread in the general
      population and does not seem to be associated with liver damage.

PMID- 11594251
TI  - The efficacy of moxifloxacin in acute exacerbations of chronic bronchitis: a
      Spanish physician and patient experience.
AB  - Chronic bronchitis is a debilitating disease affecting many millions of patients
      globally. They suffer multiple acute exacerbations each year, often requiring
      many courses of antimicrobials to enable them to return to normal. The impact of
      the condition on both the individual patient and society as a whole is
      considerable and growing; thus antimicrobial therapy should induce rapid and
      effective outcomes as soon as possible. This open, community-based study of 5737
      patients enrolled by over 2000 primary care physicians from across Spain examined
      the clinical effect of oral moxifloxacin on patients' signs and symptoms of acute
      exacerbations of chronic bronchitis (AECB) over a 45-day period. The symptoms
      were assessed using daily diary cards in addition to physician evaluations.
      Clinical assessment at day 7 showed 93.0% of patients were cured. The patient
      diary card showed that two-thirds of patients felt better by day 3 or 4. Adverse
      events were reported in 3.5% of patients in this study, the most common being
      diarrhoea, nausea and dizziness, and epigastric pain. These reactions were mild
      to moderate in intensity. There were no patient deaths due to infection during
      the study. Physicians and patients reported that once-daily moxifloxacin gave
      fast relief of symptoms of acute exacerbations of chronic bronchitis.

PMID- 11594252
TI  - Age of seizure onset in adults with Down's syndrome.
AB  - In a cohort of 68 adults (35 males and 33 females) with Down's syndrome aged 29
      83 years, a history of seizures was found in 26.5%. The overall mean age of onset
      of seizures was 37 years, males (22 years) being significantly younger than
      females (51 years). The age of onset was bimodally distributed, with the first
      peak occurring in the first two decades, and a late-onset peak occurring in the
      fifth and sixth decades. A strong association between Alzheimer's disease and
      seizures was confirmed. Of those with a history of seizures, those aged over 45
      years were significantly more likely to develop Alzheimer's disease than those
      younger than 45. It is suggested that late-onset epilepsy in Down's syndrome is
      associated with Alzheimer's disease, while early-onset epilepsy is associated
      with an absence of dementia.

PMID- 11594253
TI  - Standard cardiac rehabilitation is less effective for diabetics.
AB  - To assess clinical outcomes and lifestyle modifications in diabetic patients
      attending a standard cardiac rehabilitation programme following myocardial
      infarction (MI), a retrospective longitudinal study was undertaken in a district
      general hospital in the north west of England. A total of 1804 patients attended
      the cardiac rehabilitation programme over 10 years, of whom 223 (12.4%) had
      diabetes mellitus. Drugs were underprescribed in all patients, aspirin and beta
      blockers especially in diabetics (75.3% vs 90.3%, p < 0.0001; 38.6% vs 60.8%, p <
      0.0001). Smoking cessation was poor in diabetics (54.2% vs 69.1%, p < 0.003) and
      diabetics were less likely to attend at least one session of physiotherapy (26.9%
      vs 58.6%, p < 0.0001). Diabetics had higher mortality at one year (15.7% vs 5.6%;
      p < 0.0001), mostly associated with cardiovascular disease (13.4% vs 5.4%, p <
      0.0001). Standard cardiac rehabilitation programmes appear to be less effective
      for patients with diabetes mellitus. We suggest that patients presenting with an
      existing chronic condition need specialised programmes of rehabilitation to
      integrate the care of that condition with their recent MI. Aggressive drug
      therapy following acute MI should also be prescribed in all patients when not
      contraindicated by other evidence.

PMID- 11594254
TI  - What is the relevance of the HOPE study in general practice?
AB  - The unique findings from the HOPE (Heart Outcomes Prevention Evaluation) study
      strongly support extending the use of the angiotensin-converting enzyme (ACE)
      inhibitor ramipril as a preventive agent for patients at high risk of
      cardiovascular events with normal left ventricular function. In addition,
      ramipril provides significant benefit in diabetic patients. These findings will
      impact on how ramipril is used in primary care, where ACE inhibitors are
      currently underprescribed. Patients reflecting the inclusion criteria of the HOPE
      study should be considered as suitable candidates for long-term ramipril therapy
      as an addition to their existing drug regimen. Screening should include control
      of kidney function (by serum creatinine), particularly within the first two weeks
      of treatment, in addition to regular monitoring of serum potassium. However, the
      HOPE study shows that ramipril is well tolerated at high doses and over a long
      treatment period. The effectiveness of therapy should also be regularly reviewed
      and dose adjustments made where necessary. If concern remains, referral to a
      specialist--a cardiologist or a diabetologist--may ultimately be necessary.

PMID- 11594255
TI  - Assessment of breast problems.
AB  - Patients with discrete breast lumps, irrespective of age, should be referred for
      assessment. Premenopausal women with equivocal lumps can be re-checked two weeks
      later and, if still present or dubious, sent to a breast clinic. Almost all women
      with breast pain do not need referral unless the symptoms are severe or
      prolonged. Careful examination will detect those individuals with underlying rib
      cage pain who can be reassured and given analgesics, if necessary, but not
      referred. Blood-containing nipple discharge is an indication for referral but
      such cases can be reassured that, in the absence of a lump, it is unlikely they
      have breast cancer. Most women who suspect their family history of breast cancer
      places them at increased risk can be safely reassured and do not need to be kept
      under surveillance. All those women who are eligible for the NHS screening
      programme should be encouraged to attend when invited.

PMID- 11594256
TI  - Benign breast disease.
AB  - Benign breast disorders (BBD), classified by the ANDI system (aberrations of
      normal development and involution), constitute the major workload in breast
      clinics. Breast pain (mastalgia) is classified as cyclical, and non-cyclical
      extramammary causes such as ribircage pain have to be identified. Most patients
      need reassurance alone but those with moderate/severe pain present for > 6 months
      may need treatment: randomised trials have shown danazol, bromocriptine and
      tamoxifen to be effective. Fibroadenoma is the commonest benign solid lump in
      women aged 15-30 years. The diagnosis must be confirmed by triple assessment.
      Cysts occur usually in women of middle to late reproductive life. After
      ultrasound has confirmed the lump as cystic, it can be aspirated. Nipple
      discharge should be tested for the presence of haemoglobin (Hb). Those with HB+
      discharge may require microdochectomy for treatment and diagnosis, common causes
      being duct papilloma and duct ectasia. Breast abscesses may occur during
      lactation or in women with duct ectasia and are treated by incision or aspiration
      together with antibiotics.

PMID- 11594257
TI  - Managing gastro-oesophageal reflux disease in primary care.
AB  - The National Institute for Clinical Excellence recently issued guidance on the
      use of proton pump inhibitors (PPIs) in the management of dyspepsia, including
      gastro-oesophageal reflux disease (GORD). GORD is a common disorder that reduces
      quality of life and can indicate serious disease such as reflux oesophagitis. The
      symptoms of GORD must be distinguished from those of other diseases, such as
      functional dyspepsia or cardiac problems. Furthermore, atypical alarm symptoms,
      such as bleeding or sudden weight loss, require urgent further investigation.
      Most GORD is uncomplicated and can be treated using management algorithms that
      make the best use of resources. Newer strategies such as 'step-down' or 'on
      demand' therapy can cost-effectively improve the long-term management and quality
      of life of patients with recurrent GORD.

PMID- 11594258
TI  - Primary brain tumours: a review of research and management.
AB  - The brain is an incredibly complex organ that contains some 10 billion working
      cells. Brain tumours can arise from the brain itself, the meninges, the nerves at
      the base of the brain, or even from outside the brain. The frequency of brain
      tumours directly reflects the relative proportion of each cell type present at
      the site of the initial tumour. Symptoms produced by a brain tumour often mimic
      the symptoms of other diseases and vice versa. Because symptoms can develop
      gradually, and can be subtle, there may well be a long delay between symptom
      onset and diagnosis. Treatment of brain tumour depends on the type and stage of
      the disease, and the patient's age and overall state of health. Treatment options
      fall into three categories: surgery, radiotherapy and chemotherapy. Biological
      therapy is also being studied in clinical trials. Primary brain tumours occur in
      all age groups, but are significantly more frequent in children and adolescents
      under 15 years old and the elderly. For every person diagnosed with a brain
      tumour (over 100,000 people annually in the US), an average of 22 years of life
      expectancy is lost. The estimated annual cost, direct and indirect, of the
      disease in the US is $104 billion.

PMID- 11594259
TI  - Clinical efficacy with formoterol in the absence of a response to salmeterol: a
      review.
AB  - Salmeterol and formoterol are both beta 2-agonist bronchodilators with a long
      duration of action and are often classified together, yet they are distinctly
      different in their pharmacology. Recent evidence suggests there is a
      subpopulation of asthmatic patients who do not respond to salmeterol, yet can
      attain clinical benefit with formoterol. Following a literature search, three
      published case reports are reviewed as well as results from two published
      clinical trials designed specifically to document response to formoterol in 'non
      responders to salmeterol' asthmatics. Possible mechanisms underlying this
      observation are discussed, including pharmacological differences of the two drugs
      relating to agonism at the beta 2-receptor and to effect on nuclear transcription
      factors.

PMID- 11594260
TI  - Omalizumab, a monoclonal antibody against IgE for the treatment of allergic
      diseases.
AB  - Omalizumab, a recombinant, humanised monoclonal antibody against human IgE, will
      be introduced soon for the treatment of allergic asthma. This antibody binds
      circulating IgE molecules and inhibits the type I immune response in the lung and
      other target organs. In the phase II and III studies performed, it demonstrated a
      significant and important effect in controlling and stabilising asthma by
      reducing exacerbations and the need for inhaled corticosteroids. The safety and
      tolerability up to one year of treatment were very good. This new treatment may
      have a role in patients with difficult-to-control asthma, with recurrent
      exacerbations, and those with concurrent asthma, nose and eye symptoms.

PMID- 11594261
TI  - Rhabdomyolysis associated with varicella infection.
AB  - Varicella infection is a common childhood disease that usually resolves without
      complications. However, children under 2 months of age, adolescents, some adults
      and immunocompromised individuals are at high risk of certain rare life
      threatening complications. We report a case of primary varicella infection in an
      immunocompetent adult complicated by rhabdomyolysis. Recognition of this
      complication and aggressive fluid therapy with an antiviral agent helped to
      improve the outcome.

PMID- 11594262
TI  - Severe hyperkalaemia with normal electrocardiogram.
AB  - Elevated serum potassium without associated electrocardiograph and biochemical
      changes makes the diagnosis of pseudohyperkalaemia likely. One of the common
      causes of this is thrombocytosis with in vitro leak of cellular potassium due to
      increased fragility of the platelets. We report a case where the diagnosis of
      essential thrombocytosis was made during investigation of persistent
      hyperkalaemia in an apparently healthy female.

PMID- 11594263
TI  - The efficacy of acetazolamide on visual functions in a patient with choroid
      metastasis of breast carcinoma.
AB  - Breast carcinoma is the most frequent cancer in women and is the second leading
      cause of death. Choroid metastasis of breast carcinoma can be found either at
      presentation or in remission. It is frequently encountered in disseminated breast
      cancer with multiple organ metastasis. It has been proposed that the oedema
      reducing effect of acetazolamide is due to stimulated ion and fluid removal from
      the retina to the choroid. A 40-year-old female patient on adjuvant chemotherapy
      for breast cancer was found to have an isolated choroid metastasis. Clinical and
      radiological remission was achieved after orbital radiotherapy, chemotherapy and
      acetazolamide treatment. In this case report, we emphasise the possible
      beneficial effect of acetazolamide in patients with choroid metastasis.

PMID- 11594264
TI  - Trilobed pharyngeal diverticulum.
AB  - A previously undescribed case of a trilobed pharyngeal diverticulum is reported.
      Its presentation, radiological features and treatment are discussed.

PMID- 11594265
TI  - Thalamic tumour presenting as frontal lobe dysfunction.
AB  - A 64-year-old man presented with a change in personality and behaviour but with
      no neurological deficits. He exhibited impaired executive functions, apathy,
      unsteadiness of gait and falling; he lacked insight and exhibited purposeless
      behaviour, making loud grunting noises. A CT scan at 6 months revealed no
      abnormality, but at 9 months CT and MRI showed a bilateral thalamic tumour. The
      presenting symptoms had similarities to frontal lobe dysfunction progressing to
      dementia.

PMID- 11594266
TI  - Axillary artery pseudoaneurysm.
AB  - Axillary artery aneurysms are extremely rare. We report a case of an axillary
      artery aneurysm in a keen rugby player who had previous internal fixation of the
      shoulder for recurrent dislocation.

PMID- 11594267
TI  - Genetic testing for Gilbert's syndrome.

PMID- 11594268
TI  - [Monitoring of response to neoadjuvant therapy by positron emission tomography
      (PET)].
AB  - Neoadjuvant therapy is frequently hampered by the lack of reliable non-invasive
      techniques for prediction and assessment of response. Positron emission
      tomography using the glucose analogue 18F-fluorodeoxyglucose (FDG-PET) provides a
      unique means of non-invasive assessment of tumor metabolism. Several recent
      studies have indicated that a reduction of tumor metabolic activity after
      neoadjuvant therapy is closely correlated with the degree of histopathological
      tumor regression. The reduction of metabolic activity may also allow one to
      predict subsequent response early during the course of therapy. Therefore FDG-PET
      may permit individualized therapy management. However, there is a requirement for
      larger-scale trials to assess this technique.

PMID- 11594269
TI  - [The role of diagnostic PET in treatment planning before tumor surgery].
AB  - Positron emission tomography (PET) can be used for the noninvasive biochemical
      analysis of lesions whose benign or malignant nature cannot be assessed by
      morphological methods alone. This information and the possibility of quantitation
      are the reasons for the successful application of PET in staging, diagnosis of
      tumor recurrence and therapy monitoring in different malignant tumors. Since
      malignant tumors show characteristic biochemical properties with an enhancement
      of glucose metabolism, 18fluorodeoxyglucose (FDG) has proven useful for oncologic
      studies. This paper deals with the influence of PET on the surgical and other
      therapeutic procedures in patients with cancer of the lung, thyroid, intestine,
      breast and soft tissue. PET is useful for the mediastinal staging of patients
      with lung cancer and the evaluation of persistent tissue or tumor recurrence
      after treatment of lung cancer and colorectal cancer. Furthermore, important
      information is obtained for the staging of colorectal cancer and mammary
      carcinoma. PET is also indicated in patients with colorectal cancer or mammary
      carcinoma and a rising tumor marker. An important future application is therapy
      monitoring. New treatment modalities will raise new problems in terms of
      functional diagnosis for the different imaging procedures. Therefore, future work
      has to concentrate on the establishment of diagnostic algorithms for the
      optimization of therapy.

PMID- 11594270
TI  - [Therapy of chest wall osteomyelitis].
AB  - INTRODUCTION: Chronic osteomyelitis of the chest wall requires radical
      debridement and defect coverage with well-perfused tissue. The implantation of
      synthetic material is still under discussion because of the risk of infection.
      METHODS: A retrospective study was conducted on the complications and functional
      and aesthetic results of 26 patients with chest wall osteomyelitis after
      radiation or sternotomy treated by radical debridement and neurovascular pedicled
      latissimus dorsi muscle. RESULTS: The functional results were excellent with a
      low complication rate. The muscle showed electric activity synchronous with
      inspiration and clinically a stabilization of the thoracic defect. DISCUSSION:
      Maintained muscular activity may play an essential role for stabilizing thoracic
      defects of up to four ribs or the sternum; implantation of synthetic material is
      not necessary.

PMID- 11594271
TI  - [Outcome after laparoscopic antireflux surgery: fundoplication and re
      fundoplication in the elderly].
AB  - PURPOSE: Treatment of gastroesophageal reflux disease (GERD) in the elderly
      follows the same principles as for any adult patient. The indication for
      laparoscopic antireflux surgery (LARS) often depends on the age of the patient.
      The aim of this prospective study was to evaluate the surgical outcome including
      quality of life after LARS and laparoscopic "redo-surgery" in patients older than
      65 years. METHODS: Since 1993, 75 patients with a mean age of 71 years have been
      treated with laparoscopic "floppy" Nissen (n = 53) or Toupet (n = 22)
      fundoplication. Thirteen patients underwent laparoscopic redo-surgery after
      failed LARS. Quality of life (GIQLI) was assessed before surgery and 3 months and
      1 year after surgery, with 24-h pH monitoring and esophageal manometry being
      performed. RESULTS: Intraoperative complications occurred in two patients with
      primary LARS, successfully managed laparoscopically. The conversion and mortality
      rate was 0%. In two patients postoperative complications occurred. Three months
      and 1 year after surgery 24-h pH monitoring and esophageal manometry showed
      normal values in all patients. GIQLI increased significantly after surgery and is
      comparable to that of healthy individuals. One patient suffered from severe
      dysphagia and required dilatation. In 13 patients who underwent laparoscopic
      refundoplication, redo procedure was completed laparoscopically in 12 patients.
      In one patient conversion was necessary because of severe bleeding from the
      spleen. Data of esophageal manometry and 24-h pH monitoring showed normal values
      in all patients after redo-surgery. Three months and 1 year after laparoscopic
      reoperation the general score of GIQLI increased significantly (p < 0.01) and
      reached a level equivalent to that of comparable healthy individuals. CONCLUSION:
      Laparoscopic fundoplication and refundoplication in the elderly patient is a safe
      and effective treatment in GERD and improves quality of life significantly. Age
      should not be longer a contraindication to LARS.

PMID- 11594272
TI  - [Major vascular and neural complications in varicose vein surgery. Prospective
      documentation of complication rate in surgery of the V. saphena magna and V.
      saphena parva].
AB  - The complication rate in varicose vein surgery has not been viewed separately for
      the sapheno-femoral and the saphenopopliteal junction. From 1.10.1988 to 31.12.99
      we prospectively registered the major vascular and neural complication rate. A
      total of 31,838 ligations of the saphenofemoral junction and 6,152 ligations of
      the saphenopopliteal junction were performed. There were seven major vascular
      injuries (0.017%) and three major neural injuries (0.0074%). The specific risk at
      the saphenofemoral junction amounts to: major venous injury n = 4 (0.013%)
      without development of a postthrombotic syndrome (PTS); no arterial injury and no
      major neural injury. At the saphenopopliteal junction we found three major venous
      injuries (0.049%) with development of PTS in all cases. There were three major
      neural injuries (0.049%) with complete regeneration in two cases and one
      permanent paresis of digit V. Since operations on the saphenopopliteal junction
      show a higher risk of major vascular und major neural injury, flush ligation of
      the saphenopopliteal junction should not be forced in every case.

PMID- 11594273
TI  - [Diagnosis in suspected appendicitis. Can ultrasonography rule out acute
      appendicitis?].
AB  - INTRODUCTION: Acute appendicitis is often difficult to confirm and even harder to
      rule out by physical examination. In order to assess the diagnostic reliability
      of sonography we compared the results of physical (p) and sonographic (s)
      examination. METHOD: One hundred and fifty consecutive patients presenting with
      right lower quadrant abdominal pain were evaluated in a prospective study. Based
      on the respective findings patients were classified into three groups: I:
      appendicitis confirmed; II: appendicitis ruled out; III: equivocal findings. The
      results were compared with the discharge diagnoses established by histologic
      examination or clinical observation. RESULTS: Ultrasonography showed
      significantly higher sensitivity (group I s vs group I p: 95% vs 45%) and
      specificity (group I s vs group I p: 100% vs 75%) in confirming as well as in
      ruling out acute appendicitis (group II s vs group II p: sensitivity 73% vs 53%;
      specificity 100% vs 81%) than physical examination alone. Owing to additional
      sonographic findings the group with indeterminate abdominal pain was much smaller
      after ultrasound examination (group III s vs group III p: 35 vs 69 patients).
      CONCLUSIONS: After discussing the literature and sonomorphologic criteria that
      distinguish an inflamed from a normal appendix, we conclude that ultrasonography
      is a valuable tool in confirming as well as in ruling out acute appendicitis.

PMID- 11594274
TI  - [Postoperative pyoderma gangrenosum].
AB  - Post-traumatic pyoderma gangrenosum is an ulceronecrotizing dermatosis that is
      rare and therefore often misinterpreted. After excision of an orbit pseudotumor
      by otorhinolaryngological surgeons, a 77-year-old woman developed a multifocal
      ulcerous wound dehiscence. Although the case history, development and clinical
      picture were characteristic, the correct diagnosis was established and
      successfully treated 6 months later by a consulting dermatologist. Postoperative
      pyoderma gangrenosum should be taken into consideration if a sterile, painful,
      chronically progressive, ulcerative and sludgy defect develops after surgery. The
      preoperative investigation should include pyoderma gangrenosum in the personal
      history and take associated diseases into account (e.g., inflammatory bowel
      diseases, blood diseases, rheumatological diseases and vasculitis) to provide
      prophylactic immunosuppressive pharmacotherapy. In minimally invasive or cosmetic
      surgery these aspects may have a forensic impact, as pyoderma gangrenosum heals
      with atrophic scars. The purpose of this paper was to describe the clinical
      characteristics of pyoderma gangrenosum, its prevention and its therapy.

PMID- 11594275
TI  - [Bronchial anastomoses after lung transplantation: results with single running
      suture technique].
AB  - BACKGROUND: The standard technique for the bronchial anastomosis in LTX is a
      running suture on the membranous and single stitches on the cartilaginous portion
      of the bronchus. The aim of this retrospective study was to compare the results
      of this technique to the new single running suture technique. METHODS: Between
      January and December 1998, 56 consecutive single (n = 17) and bilateral (n = 39)
      lung transplants in 52 patients were performed. Eighty-three bronchial
      anastomoses were retrospectively analyzed and evaluated by separating into two
      groups: group 1 (24 patients, 39 anastomoses) with standard technique and group 2
      (24 patients, 44 anastomoses) with single running suture. The two groups were
      comparable with regard to age, primary diagnosis, intraoperative use of
      extracorporeal circulation, ischemia time, duration of mechanical ventilation,
      ICU and number of acute rejections/100 days. Bronchial healing was assessed with
      bronchoscopic follow-up (5-16 months). RESULTS: Primary excellent airway healing
      was observed in 36 anastomoses (92%) in group 1 and in 41 (93%) in group 2. In 2
      anastomoses in group 1 (5%) and in 2 anastomoses in group 2 (4.6%) necrosis less
      than 5 mm was observed. In one anastomosis in group 1 (2.7%) a 10-mm bronchial
      necrosis with partial occlusion of the bronchial lumen by necrotic tissue
      necessitated temporary intraluminal stenting. In one anastomosis in group 2
      (2.3%) malacia of the bronchus intermedius occurred. CONCLUSION: The single
      running suture technique for bronchial anastomosis is a safe technique providing
      the same results as the established technique and we advocate its use for
      bronchial anastomosis.

PMID- 11594276
TI  - [Video-assisted hemithyroidectomy: surgical technique and early results].
AB  - To date, there are only very few data on minimally invasive thyroid surgery. In a
      prospective study (11/99-11/00), videoscopically assisted hemithyroidectomy was
      performed on 18 patients (3 M, 15 F; age 22-56 years) with uninodular thyroid
      disease. The length of the cervical incision was between 15 and 25 mm; 8 patients
      were operated on using initial gas insufflation and 10 patients with a gasless
      technique. The mean operative time was 96 +/- 23 min, significantly longer than
      in a conventionally operated group (n = 26) during the same period. No
      complications were observed. Videoscopically assisted hemithyroidectomy is
      feasible and can be considered in selected patients.

PMID- 11594277
TI  - [Determination of therapy management in rectal carcinoma by staging with 18-FDG
      PET].
AB  - The curative treatment of carcinoma of the rectum in the early stage of the
      disease is radical local surgery. If there is a solitary liver metastasis,
      resection is also a curative treatment. This report describes a female patient
      with rectal carcinoma, in whom a solitary liver metastasis in the left lobe was
      diagnosed only by FDG-PET and verified at surgery. This case report demonstrates
      the potential role of FDG-PET even for primary staging in detecting occult
      hepatic and extrahepatic metastases, thus significantly influencing the
      therapeutic management and prognosis of these patients.

PMID- 11594278
TI  - [Pulmonary nodular amyloidosis mimicking multiple pulmonary metastases of
      carcinoma of the corpus uteri].
AB  - INTRODUCTION: Pulmonary nodular amyloidosis (PNA) is a phenomenon that is rarely
      diagnosed anywhere in the world. METHODS: We report a case of a 63-year-old woman
      who smoked in whom a chest X-ray examination 5 years after diagnosis and radical
      treatment of a highly differentiated carcinoma of the corpus uteri showed
      multiple lung metastasis. To elucidate these findings by bronchoscopy and
      thoracoscopy we took a specimen from the right pleura and from one of the
      suspicious nodules, which were up to 3 cm in diameter; we also obtained some of
      the bronchial secretion. RESULTS: The nodules were histopathologically diagnosed
      as PNA. CONCLUSION: Even if it is rare, PNA also belongs in the differential
      diagnosis of metastatic cancers. For us evidence of Pseudomonas fluorescens in
      the sputum is a reason for discussing a chronic, clinical unobtrusive local
      inflammation with hyperactivity of the B-cells as the hypothetical etiology of
      the amyloidomas.

PMID- 11594279
TI  - [Aortic rupture in Behcet's disease].
AB  - Behcet's disease is a vasculitis of unknown aetiology, which becomes apparent by
      ocular and mucocutaneous symptoms. In rare cases, owing to vasculitis of the vasa
      vasorum of large arteries, necrosis of the vascular wall and thus spurious
      aneurysms occur. The case of a 41-year-old patient is described who presented
      with a rupture of an infrarenal aortic aneurysm due to Behcet's disease. Therapy
      consisted of placement of an aortic-aortic Dacron prosthesis. On the basis of the
      case report, the diagnostic approach, the therapy and the value of secondary
      prophylaxis of Behcet's disease are discussed.

PMID- 11594280
TI  - [Clinical value of positron emission tomography (PET) in the diagnosis of bone
      and soft tissue tumors. 3rd Interdisciplinary Consensus Conference "PET in
      Oncology": results of the Bone and Soft Tissue Study Group].
AB  - PURPOSE: In the framework of the 3rd Consensus Conference "PET in Oncology" the
      bone and soft-tissue tumors study group evaluated the present position of PET for
      these tumor entities on the basis of international publications. METHODS: After a
      systematic review of the literature, publications were evaluated according to
      previously defined quality criteria. For various indications the clinical
      usefulness of PET was assessed using a classification system. RESULTS: Most
      studies had been performed with a small number of patients (n < 35). Therefore,
      only 8 of 46 publications were judged relevant. On the basis of these literature
      data, use of FDG-PET for grading was classified 1b (literature results
      predominantly show clinical usefulness). As before (1995/97), all other
      indications were categorized with 3 (assessment not yet possible, literature data
      inadequate). OUTLOOK: According to the opinion of experts, the detection of
      osseous metastases of Ewing's sarcoma, therapy monitoring and the diagnosis of
      recurrences are potentially useful clinical indications for FDG-PET. Therefore,
      prospective studies with large patient groups are essential to further evaluate
      the benefit of FDG-PET in these indications.

PMID- 11594281
TI  - [Internet presence in surgical departments in Germany. II. Legal bases of medical
      Internet presence].
AB  - In recent years, the Internet has generally been growing throughout the world,
      and physicians have taken to the Web as well. Besides its use for medical data
      research, physicians and hospitals are increasingly discovering the Internet as a
      vehicle for the presentation of their scope of practice. In this regard, the
      legal frameworks in Germany are strictly regulated. This article presents current
      legal standards and consequences to be faced when the law on prohibited
      advertising is broken. Included are references to specific laws concerning
      Internet pages.

PMID- 11594282
TI  - [Laparoscopic appendectomy and conventional preparation technique].

PMID- 11594283
TI  - [Legal questions for surgeons].

PMID- 11594284
TI  - [Fluorodeoxyglucose positron emission tomography (FDG-PET) in the differential
      diagnosis of pancreatic lesions].
AB  - Various diagnostic modalities have been introduced for the diagnostic work-up of
      suspected pancreatic cancer. However, the differentiation of pancreatic cancer
      and chronic pancreatitis is still a challenge. Positron emission tomography (PET)
      with radiolabeled fluorodeoxyglucose (FDG) is an imaging modality that is based
      on the increased glucose metabolism of malignant cells. In contrast to
      conventional imaging, which provides morphological information, FDG-PET
      demonstrates functional alterations of malignant tumours. The value of FDG-PET in
      differentiating pancreatic lesions has been validated by numerous studies with
      variable patient selection criteria. In these studies a sensitivity between 71%
      and 100% and a specificity between 64% and 100% was reported. The median
      sensitivity was 92% and the median specificity 82%. The diagnostic accuracy was
      limited in hyperglycemic patients and in patients with active inflammation of the
      pancreas, as is found in acute pancreatitis or active chronic pancreatitis. These
      limitations have to be taken into account for the indication of FDG-PET as well
      as the interpretation of PET findings.

PMID- 11594285
TI  - [Influence of positron emission tomography on surgical therapy planning in
      recurrent colorectal cancer].
AB  - The advantages of PET are high sensitivity and specificity for the detection of
      local tumor relapse, especially in comparison with conventional imaging
      techniques. Furthermore, there is an additional value of FDG-PET for the
      detection of tumor manifestations associated with a tumor marker (e.g. serum CEA)
      increase without suspicious findings in other diagnostic procedures. The
      methodological advantage of a whole-body examination further improves the
      detectability of distant metastases. Thus, FDG-PET may induce a change in the
      therapeutic concept in recurrent colorectal cancer in approximately 30% of cases,
      concerning the indication for surgery as well as the use of multimodal surgical
      concepts. By means of the metabolic functional approach FDG-PET offers the
      possibility of therapy monitoring. This enables very early and more specific
      indication of response to preoperative therapies or of the presence of residual
      disease after surgical tumor resection or interventional tumor ablation of
      metastases or recurrences. PET using new tracer molecules demonstrates an
      additional advantage of the technique regarding the determination of the
      micromilieu of a tumor (vascularity, proliferation) compared with all other non
      invasive diagnostic methods. This opens up new possibilities to optimize surgical
      therapy planning and prognostic evaluation.

PMID- 11594286
TI  - [Comments on the DRG system from the viewpoint of the trauma surgeon].

PMID- 11594287
TI  - [DRG: hostile to MIC?].

PMID- 11594288
TI  - [DRG exercises].

PMID- 11594289
TI  - [Maternal welfare for women physicians].

PMID- 11594290
TI  - [Surgical profession during pregnancy].

PMID- 11594291
TI  - Beta cell failure: causes and consequences.
AB  - In recent years a great deal of discussion has focused on the relative roles of
      insulin resistance and beta-cell dysfunction in the pathogenesis of type 2
      diabetes. When considering their relative importance it is critical that the two
      variables are considered in concert. Alterations in insulin secretion are present
      in patients with type 2 diabetes and can be demonstrated in high risk individuals
      well before diagnosis. Loss of the early phase of insulin secretion can be
      demonstrated following oral or intravenous glucose administration. The
      relationship of early insulin secretion to insulin sensitivity in normal
      individuals is represented by a hyperbolic curve in keeping with the existence of
      a feedback loop. Deviations from standardised curves demonstrate defects in both
      insulin secretion and sensitivity in individuals who are at risk of developing
      diabetes. The reduction in the early phase insulin response results in impaired
      suppression of hepatic glucose production. Glucose output by the liver is not
      inversely proportionate to glucose influx, resulting in postprandial
      hyperglycaemia. Therapeutic approaches must address defects in both the early
      insulin response and insulin sensitivity. New oral agents that stimulate early
      insulin secretion and rapid-acting insulin analogues are targeting this early
      insulin secretion defect.

PMID- 11594292
TI  - Current strategies for controlling postprandial hyperglycaemia.
AB  - In patients with diabetes mellitus glycosylated haemoglobin (HbA1c), which
      reflects mean glycaemic values in the previous 3 months, is typically used as a
      clinical measure of blood glucose control. However, it does not always correlate
      satisfactorily with postprandial blood glucose excursions, which may occur only
      for a few hours and be insufficient to alter HbA1c formation. Thus, postprandial
      glucose peaks may have a significant impact on diabetic complications but not be
      monitored sufficiently from HbA1c measurements. Epidemiological studies have
      shown stronger correlations for incidence of cardiovascular events with
      postprandial glucose levels than with preprandial levels. Results from the UKPDS
      suggest that HbA1c had to be reduced below 7 per cent to ameliorate macrovascular
      outcomes. In patients with type 2 diabetes there is a loss of the first phase
      insulin response so a logical treatment strategy is to use a rapid-acting insulin
      analogue. Rapid-acting insulin analogues have a greater effect on postprandial
      glucose levels than regular human insulin. This is due to the faster absorption
      and higher insulin peak in blood, but also due to the increased ability of rapid
      acting analogues to suppress hepatic glucose release. In clinical practice,
      preprandial injection of rapid-acting insulin reveals significant advantages
      including treatment flexibility, lack of weight gain, stable insulin doses and
      reduction of hypoglycaemic episodes. These effects are more pronounced if this
      type of therapy is used early in the course of the disease. Thus rapid-acting
      insulin analogues are being increasingly used as first-line therapy with multiple
      daily injection in patients with type 2 diabetes.

PMID- 11594293
TI  - The importance of postprandial hyperglycaemia in development of cardiovascular
      disease in people with diabetes: point.

PMID- 11594294
TI  - The importance of postprandial hyperglycaemia in development of cardiovascular
      disease in people with diabetes: counterpoint.

PMID- 11594295
TI  - Hyperglycaemia: link to excess mortality.
AB  - Asymptomatic diabetes is defined by chronic hyperglycaemia. The 2-h post
      challenge glucose level is not generally used in practice and consequently not
      recommended for diagnosis, so diabetes is defined from fasting hyperglycaemia.
      Several large studies have been used to evaluate the impact of different
      diagnostic definitions on the risk of premature death. Meta-analysis of component
      studies in the Diabetes Epidemiology: Collaborative Analysis of Diagnostic
      Criteria in Europe (DECODE) study showed that for all-cause mortality fasting
      glucose did not carry an independent risk but the 2-h post-challenge glucose
      carried a significant risk after adjusting for factors including fasting glucose.
      Increasing fasting glucose also did not carry a significant excess risk for
      cardiovascular mortality but there was an overall significant relative risk with
      increasing 2-h post-challenge glucose. Analysis of 20-year follow-up data from
      the combined Whitehall, Paris and Helsinki studies demonstrated that after
      adjusting for other risk factors men in the upper 20 per cent of the 2-h glucose
      distribution and those in the upper 2.5 per cent for fasting glucose had a
      significantly higher risk of all-cause mortality compared with men in the lower
      80 per cent of each distribution. Analysis of the Paris Prospective study alone
      showed that all-cause mortality was highest in those with isolated 2-h post
      challenge hyperglycaemia. In men without known diabetes there were J-shaped
      relationships between both fasting and 2-h glucose and all-cause, cardiovascular
      and cancer mortalities. Fasting and 2-h glucose levels are highly correlated and
      hyperglycaemia by either definition is undoubtedly a risk factor for premature
      death, whatever the cause.

PMID- 11594296
TI  - Hypoglycaemia and cognitive function in diabetes.
AB  - The human brain is almost totally dependent on a continuous supply of glucose,
      deprivation of which rapidly causes malfunction. In the brain there are regional
      differences in the susceptibility to neuroglycopenia with the cerebral cortex
      being most sensitive while deeper structures are more resistant. A fall in blood
      glucose provokes a hierarchy of responses including secretion of counter
      regulatory hormones and development of warning symptoms which alert the
      individual to treat the hypoglycaemia. Symptoms are generated when blood glucose
      falls to specific threshold concentrations, although these are dynamic and can be
      modified by various factors. Symptoms can be classified as autonomic and
      neuroglycopenic, with the latter being related to altered cognitive functioning.
      Acute hypoglycaemia produces electroencephalographic (EEG) changes as well as
      neurophysiological abnormalities including increased latency and/or reduced
      amplitude of sensory evoked potentials. At blood glucose below 3 mmol/l cognitive
      functioning becomes impaired but the degree of dysfunction differs in various
      domains and a battery of psychometric tests are required to assess impairment of
      cognitive function during hypoglycaemia. Complex, attention-demanding and speed
      dependent responses are most impaired with accuracy often preserved at the
      expense of speed. Cognitive function does not recover fully until 40-90 min after
      blood glucose is restored to normal. Hypoglycaemia also provokes changes in mood,
      increases anxiety and may induce depression and fear of further hypoglycaemia,
      which can modify behaviour and influence quality of glycaemic control. Recurrent
      severe hypoglycaemia may have long-term sequelae in the form of cumulative
      cognitive impairment and impaired awareness of hypoglycaemia.

PMID- 11594297
TI  - Driving mishaps and hypoglycaemia: risk and prevention.
AB  - Driving is a complex, multi-task activity that can be affected by cognitive
      impairment resulting from episodes of severe hypoglycaemia. Intensive insulin
      therapy increases the likelihood of severe hypoglycaemia but there have been few
      studies examining effects on driving skills. A survey carried out recently
      indicated that patients with type 1 diabetes had twice the incidence of driving
      accidents than their non-diabetic spouses or patients with type 2 diabetes. The
      motor accidents were associated with more frequent low blood glucose while
      driving and less frequent self-monitoring. In driving simulation tests it was
      found that driving has an intrinsic metabolic demand that can contribute to
      hypoglycaemia. Driving performance began to deteriorate at around 3.6 mmol/l but
      drivers frequently did not recognise and failed to treat the hypoglycaemia. Those
      who did self-treat had more driving relevant symptoms and less neuroglycopenia
      quantified by EEG alpha-theta differences. Patients should be recommended not to
      begin driving if blood glucose is below 4.5 mmol/l and should not continue to
      drive if they suspect that blood glucose has fallen below 4 mmol/l while driving.
      If hypoglycaemia is suspected patients should immediately pull off the road,
      measure blood glucose if possible, treat themselves as necessary and not resume
      driving until glucose and cognitive-motor function return to normal. The problems
      of driving and hypoglycaemia should be discussed with patients with diabetes and
      behavioural interventions instigated. To this end, Blood Glucose Awareness
      Training (BGAT) and Hypoglycaemia Anticipation, Awareness and Treatment Training
      (HAATT) have been developed and shown to markedly reduce incidence of driving
      mishaps.

PMID- 11594298
TI  - Continuous blood glucose monitoring: detection and prevention of hypoglycaemia.
AB  - For patients with diabetes the best defence against the consequences of either
      hypoglycaemia or hyperglycaemia is to be able to recognise it and treat it
      promptly. In normal activity patients have problems in their diabetes management
      despite adequate knowledge and therapies. Glucose sensors have been developed
      that can be inserted subcutaneously in order to continuously monitor glucose
      concentrations over several days. Studies have been conducted with continuous
      glucose monitoring of patients with diabetes that reveal previously unrecognised
      periods of hypoglycaemia, ranging from a few minutes to several hours. Continuous
      monitoring during the nocturnal period can reveal hypoglycaemic and
      hyperglycaemic episodes and the insulin usage can subsequently be adjusted to
      decrease the incidence, which may lead to reduction in the risk of long-term
      complications. Preliminary studies have already shown that better management can
      be obtained, with reductions in HbA1c levels, when 24-h profiles of glucose
      concentrations are obtained. Our ongoing study of patients with type 1 diabetes
      assessing continuous glucose monitoring have shown that glucose concentrations
      are only within a target range of 4-10 mmol/l for about 35 per cent of the time.
      Such measurements are leading to better individualisation of diabetes management.
      While the present generation of glucose monitors only provide retrospective
      profiles, newer sensors are being developed that can detect real-time changes.
      These may form the basis of an alert to hypoglycaemic levels or ultimately be
      connected directly to continuous insulin infusion, particularly with rapid-acting
      insulin analogues, to maintain glucose within normal physiological limits.

PMID- 11594299
TI  - Insulin pump therapy and rapid acting insulin: what have we learned?
AB  - Approximately 80 years after the discovery and first human use of insulin, we are
      still striving to replace insulin in a physiological manner. The development of
      insulin analogues with superior pharmacokinetics has made mimicking of meal and
      basal insulin requirements by subcutaneous injection more feasible.
      Administration by continuous subcutaneous insulin infusion (CSII) has provided
      additional flexibility in meal timing and modifying basal insulin replacement in
      response to circadian rhythms. Several studies have documented improved glycaemic
      control with CSII using a rapid-acting analogue such as insulin lispro, compared
      with regular human insulin. Lower postprandial glucose peaks and improved HbA1c
      levels were seen with insulin lispro by CSII. In addition, the frequency of
      hypoglycaemia was significantly reduced and the counter-regulatory hormone
      responses were maintained. The use of insulin lispro in CSII, compared with
      regular human insulin, resulted in improved hepatic glucose output in response to
      glucagon. The potential for problems of hyperglycaemia and ketoacidosis with
      interruption of insulin delivery by CSII has been studied. One study showed
      accelerated development of hyperglycaemia and ketosis with insulin lispro
      compared with regular human insulin while another showed no difference but return
      to normal glycaemia was faster when insulin lispro was administered. The use of
      CSII in the US has grown from 6,600 in 1990 to over 100,000 patients currently.
      With improved insulins, better methods of delivery and advances in glucose
      monitoring we will continue progress towards physiological insulin replacement
      and reduce the long-term complications of diabetes.

PMID- 11594300
TI  - Mechanisms of tissue damage in the postprandial state.
AB  - There is increasing evidence that the postprandial state is an important
      contributing factor to the development of atherosclerosis. In diabetes, the
      postprandial phase is characterised by a rapid and large increase in blood
      glucose levels and the possibility that the postprandial hyperglycaemic peaks may
      be relevant to the pathophysiology of late diabetic complications has recently
      received much attention. The oral glucose tolerance test, although highly non
      physiological, has commonly been used as the model of the postprandial state.
      Epidemiological studies have shown that, when impaired, oral glucose tolerance is
      associated with an increased risk of cardiovascular disease, with the glycaemia
      two hours after the glucose challenge a direct and independent risk factor.
      Moreover, the possibility that postprandial hyperglycaemia is also a risk factor
      for cardiovascular disease in diabetic patients has been reported. Most of the
      cardiovascular risk factors are modified in the postprandial phase in patients
      with diabetes and are directly affected by an acute increase in glycaemia. The
      mechanisms through which acute hyperglycaemia exerts its effects may be
      identified as labile non-enzymatic glycation and production of free radicals. It
      is likely that the two mechanisms co-operate in causing the disorders induced by
      acute hyperglycaemia. Correcting the postprandial hyperglycaemia can form part of
      the strategy for the prevention and management of cardiovascular disease in
      diabetes.

PMID- 11594301
TI  - Chief executives. Staying afloat.
AB  - A study of chief executives identified the ability to prioritize, clear vision,
      resilence, and willingness to take decisions as key factors in success. Some
      wanted more active involvement from the regional director. Chief executives could
      be subject to 360-degree assessment. More work is needed to establish the
      compatibility of chief executives and chairs.

PMID- 11594302
TI  - General practice. Resigned to the job.
AB  - More than half the GPs in the UK have said they will consider resigning from the
      NHS if the government will not agree improvements in their contracts. GPs have
      been threatening to resign from public healthcare in the UK for the past 90
      years. In March 1948, 90 per cent of doctors voted against the proposed NHS. By
      September 1948, 90 per cent of GPs had signed up with the NHS. GPs' threats to
      resign need to be seen in the context of history.

PMID- 11594303
TI  - 10 cheap and easy ways to improve food service.

PMID- 11594304
TI  - Virtual learning web site leads the VA to success.

PMID- 11594305
TI  - Internet usage.

PMID- 11594306
TI  - Hospital CEO turnover remains stable in 2000.

PMID- 11594307
TI  - Don't drop the Slop!

PMID- 11594308
TI  - What is the role of currently available sunscreens in the prevention of melanoma?

PMID- 11594309
TI  - No need for sunscreen or occlusive dressings for benign naevi during routine
      phototherapy.

PMID- 11594310
TI  - National Highway Safety Administration. Automatic collision notice field test
      summary.
AB  - From 1995 to 2000, the National Highway Traffic Safety Administration (NHTSA)
      sponsored an initiative to create and operate an Automatic Collision Notification
      (ACN) system on a demonstration basis in a rural area to provide faster and
      smarter emergency medical responses and in an attempt to save lives and reduce
      disabilities from injuries. This article is a brief summary of that
      demonstration.

PMID- 11594311
TI  - Preoperative autologous deposit must be employed properly to utilize its
      potential.

PMID- 11594312
TI  - Hemoglobin-based blood substitutes for Jehovah's Witnesses.

PMID- 11594313
TI  - Bone densitometry in clinical practice: longitudinal measurements at three sites
      in postmenopausal women on five treatments.
AB  - We report sequential changes in bone mineral density (BMD) at the forearm, hip
      and spine in 340 consecutive postmenopausal women referred by 103 general
      practitioners and six specialists, and who were either untreated or being treated
      with calcium, estrogen, norethisterone or calcitriol for a median period of 25
      months (range 11-52). The mean annual rate of change in BMD at the three sites
      was: 1.39% in 44 women on norethisterone; 0.94% in 107 women on estrogen (both p
      < 0.001); 0.24% (not significant) in 52 women on calcitriol; -0.53% in 92 women
      on calcium; and -1.06% in 45 women on no treatment (both p < 0.01). The mean
      annual rate of change at the three sites in the 295 treated women was 0.43%,
      which was significantly positive (p < 0.001) and was 1.49 percentage points more
      positive than in the untreated women (p < 0.001). The greatest mean difference
      between treated and untreated patients was seen at the forearm, where it was 2.16
      percentage points (p < 0.001). This was significantly greater than the difference
      at the femoral neck (1.21 percentage points (p = 0.037)) and lumbar spine (1.10
      percentage points (p = 0.044)). The data did not change significantly after
      correction for age, years since menopause or baseline BMD. Those who started the
      treatments at baseline gained bone faster than those who were continuing on
      existing therapies, but this difference was not significant at any site. In the
      hormone- and calcitriol-treated groups, there was no significant difference
      between those who had a calcium supplement and those who did not. We conclude
      that the effects of treatment on BMD in clinical practice are comparable to those
      predicted from clinical trials, that there are significant differences between
      the responses to treatment at different sites and that the forearm appears to be
      the most sensitive site, in this series at least.

PMID- 11594314
TI  - [Endometriosis. Symptoms and diagnosis. 1946].

PMID- 11594315
TI  - Economics of surgery.
AB  - The time has come to subject surgery to the same rigours of economic assessment
      that other health-care sectors are already receiving--namely, the comparative
      assessment of costs and benefits. The surgical management of gallstones provides
      a good example of the role of economics in surgery. Gallstone disease is common
      and patients are usually referred to a surgeon, but the threshold for
      intervention is not agreed and varies widely, with considerable implications for
      resources. Gallstone removal has been subject to much innovation over the past 10
      years, yet economic assessment of laparoscopic and "mini" cholecystectomy and of
      gallstone lithotripsy is rare, despite the fact that operation rates have
      increased by up to 50% in some countries. For surgery to compete with other
      interventions, economic assessment of new surgical techniques will be
      increasingly important. This assessment should be based on well-conducted
      clinical trials in which interventions are provided in a routine service setting,
      and in which benefits are assessed among other things on the basis of the
      patient's perceived quality of life. Economic assessment often needs data beyond
      those collected in a clinical trial, however pragmatic the trial design, so
      modelling will often be required, incorporating a range of sources of evidence.
      Finally, evidence alone will not be enough to promote cost-effective practices.
      The take-up of surgical techniques will always be affected by the way hospitals
      and surgeons are remunerated. Affecting practice requires a realistic system of
      reimbursement that reflects evidence on cost effectiveness.

PMID- 11594316
TI  - Thomas Bowdler: censor, philanthropist, and doctor.
AB  - A recent biography of the physician William Osler credits him with having
      generated a verb, to "oslerize", as a synonym for euthanasia. Actually, Osler had
      been mocking his own impending senescent uselessness at the time of his move from
      Baltimore to Oxford. That neologism did not last. Two earlier doctors who did
      make it to the dictionaries in a verbally eponymous way were F A Mesmer and
      Thomas Bowdler, and Bowdler, at least, would not have liked the recognition. The
      first use of the verb to "bowdlerise" seems to have been in 1836, with a
      reference to "names in the writings of the apostles which modern ultrachristians
      would probably have Bowdlerized". However, Bowdler is better remembered for his
      cleaning up of the plays of Shakespeare.

PMID- 11594317
TI  - Breastfeeding in HIV-1-positive mothers.

PMID- 11594318
TI  - Breastfeeding in HIV-1-positive mothers.

PMID- 11594319
TI  - Breastfeeding in HIV-1-positive mothers.

PMID- 11594320
TI  - Effects of world trade on public health.

PMID- 11594321
TI  - WHO report 2000.

PMID- 11594322
TI  - WHO report 2000.

PMID- 11594323
TI  - Incidence of cancer.

PMID- 11594324
TI  - Long delays in seeking treatment for schizophrenia.

PMID- 11594325
TI  - Antimicrobial resistance potential.

PMID- 11594326
TI  - Antimicrobial resistance potential.

PMID- 11594327
TI  - Antimicrobial resistance potential.

PMID- 11594328
TI  - Placebos and pain management.

PMID- 11594329
TI  - The life of refugees.

PMID- 11594330
TI  - The life of refugees.

PMID- 11594331
TI  - Radiation nephropathy caused by yttrium 90.

PMID- 11594332
TI  - Pure powder and intellectual property.

PMID- 11594333
TI  - Maintenance of abstinence from alcohol.

PMID- 11594335
TI  - Detection of calcium and calmodulin during spermiogenesis of phytophagous bugs
      (Hemiptera: Pentatomidae).
AB  - The ultrastructural detection of calcium using pyroantimonate, and the
      immunocytochemical localization of calmodulin using monoclonal antibody were
      carried out during the spermiogenesis of phytophagous bugs. The presence of
      calcium was observed on the Golgi apparatus during the initial phases of
      spermiogenesis. In the other stages the calcium was observed in association with
      the nucleus and in some regions of acrosome. Indeed, it was detected surrounding
      the mitochondrial derivatives and specific axonemal microtubules on the tail
      region. The immunocytochemical detection of calmodulin showed the presence of
      this protein approximately in the same regions where the calcium was detected,
      indicating that calcium and calmodulin could work together during spermiogenesis
      of this phytophagous bugs, suggesting their involvement on the regulation of
      flagellar beating, nuclear compactation and acrosome formation.

PMID- 11594336
TI  - Open to the world.

PMID- 11594334
TI  - Somatic embryogenesis in Asparagus officinalis L. cv. Argenteuil: interactions
      between genotype, explant type and growth regulators on callus induction, growth
      and embryogenic differentiation.
AB  - Callus induction, growth and embryogenic differentiation were studied in two
      selected genotypes of Asparagus officinalis L. cv. Argenteuil, to develop a
      protocol for somatic embryogenesis. Two experiments were carried out. In the
      first, four explant types (spear sections and lateral buds, both of in vivo and
      in vitro origin), and three levels of 2,4-D (1.5, 5 and 10 mg.l-1) and two of KIN
      (0 and 1 mg.l-1) added to MS basal medium, were tested during the three initial
      culture stages (90 d period). All factors were included in one factorial design
      to statistically analyze interaction effects. Interactions between genotype,
      explant type and time of culture initiation were significant for callus induction
      and growth during the two initial culture stages. The addition of kinetin
      enhanced callus induction and growth, and high levels of 2,4-D depressed callus
      growth. The average embryogenic differentiation was < 2% overall (11% with the
      best factor combination). In the second experiment, another explant type (bud
      clusters) was tested; the average embryogenic differentiation was 1.9% (best
      combination: 5.6%). For the two genotypes studied, the best factor combinations
      were the culture of in vivo lateral buds or bud clusters on MS basal medium with
      1.5 mg.l-1 2,4-D and 1 mg.l-1 KIN.

PMID- 11594337
TI  - Surveillance or surgery? A description of the factors that influence high risk
      premenopausal women's decisions about prophylactic oophorectomy.

PMID- 11594338
TI  - Oncology nurse training in cancer genetics.

PMID- 11594339
TI  - Participation in preconceptional carrier couple screening: characteristics,
      attitudes, and knowledge of both partners.

PMID- 11594340
TI  - Functional characterisation of mitochondrial tRNA(Tyr) mutation (5877-->GA)
      associated with familial chronic progressive external ophthalmoplegia.

PMID- 11594341
TI  - Mutation detection in long QT syndrome: a comprehensive set of primers and PCR
      conditions.

PMID- 11594342
TI  - Triplication of several PAR1 genes and part of the Homo sapiens specific
      Yp11.2/Xq21.3 region of homology in a 46,X,t(X;Y)(p22.33;p11.2) male with
      schizophrenia.

PMID- 11594343
TI  - Potential mapping of corneal dermoids to Xq24-qter.

PMID- 11594344
TI  - Satellites on the terminal short arm of chromosome 12 (12ps), inherited through
      several generations in three families: a new variant without phenotypic effect.

PMID- 11594345
TI  - Introduction.

PMID- 11594346
TI  - Influence of ancillary genes, encoding aspects of methionine metabolism, on
      tylosin biosynthesis in Streptomyces fradiae.
AB  - The tylosin-biosynthetic (tyl) gene cluster of Streptomyces fradiae contains
      ancillary genes that encode functions normally associated with primary
      metabolism. These can be disrupted without loss of viability, since equivalent
      genes (presumably used for 'housekeeping' purposes) are also present elsewhere in
      the genome. The tyl cluster also contains two genes that encode products unlike
      any proteins in the databases. Two ancillary genes, metF (encoding N5,N10
      methylenetetrahydrofolate reductase) and metK, encoding S-adenosylmethionine
      synthase, flank one of the 'unknown' genes (orf9) in the tyl cluster. In a strain
      of S. fradiae in which all three of these genes were disrupted, tylosin
      production was reduced, although this effect was obscured in media supplemented
      with glycine betaine which can donate methyl groups to the tetrahydrofolate pool.
      Apparently, one consequence of the recruitment of ancillary genes into the tyl
      cluster is enhanced capacity for transmethylation during secondary metabolism.

PMID- 11594347
TI  - When the central executive lets us down: schemas, attention, and load in a
      generative working memory task.
AB  - Participants were asked to generate a single sequence of numbers in between two
      bounds. By varying the requested sequence length and way in which the question is
      posed, this paradigm enables assessment of the contributions to central executive
      functioning of schema, focus of attention, and load. With sequences of three or
      four numbers, a quarter of the sample failed fully to comply with the
      instructions. They generated an incorrect number of numbers or went outside the
      specified bounds. With sequences of six numbers, more than half of the sample
      infringed one or more of the constraints. Participants consistently generated
      sequences with particular generic properties. The overall frequency and patterns
      of infringements suggest that a substantial proportion of participants focused
      their conceptual attention on sequence content and often neglected the problem of
      how thelength and boundary constraints were going to be evaluated either before
      or during response delivery.

PMID- 11594348
TI  - Patterns of errors in short-term forgetting in AD and ageing.
AB  - This study examined whether the low performance of 40 AD patients in the Brown
      Peterson task could be explained by a pattern of errors that differed from 55
      elderly controls. Our quantitative results showed that AD patients had a lower
      performance level in the three retention intervals than controls but a
      significant interaction between group and interval was not found, indicating that
      the rate of forgetfulness was similar in the two groups. In our qualitative
      analysis, errors were categorised as confusions, perseverations, omissions, and
      order alterations. Contrary to other studies (Dannenbaum, Parkinson, & Inman,
      1988; Kopelman, 1985) where an AD forgetfulness tendency of omissions was
      observed, our data showed an excess of perseveration (even more than five
      repetitions), indicating problems in the central executive. This could be
      interpreted in terms of problems in updating the contents of working memory.

PMID- 11594349
TI  - How does the severity of a learning disability affect working memory performance?
AB  - Working memory performance was examined in children aged 11-12 years who had
      borderline, mild, and moderate learning disabilities. Comparisons with children
      of average abilities were used to determine whether those with more severe
      learning disabilities had greater impairments in working memory. Seven measures
      of working memory span were used to assess temporary phonological short-term
      storage (digit span, word span), temporary visuo-spatial short-term storage
      (pattern span, spatial span), and temporary short-term storage with additional
      processing, or central executive, demands (listening span. odd one out span,
      reverse digit span). Children with mild and moderate learning disabilities were
      impaired on all measures of working memory compared to children of average
      abilities. Children with borderline learning disabilities were just as good as
      children with average abilities on visuo-spatial and complex span tasks, but
      showed an impairment on phonological span tasks. Children with moderate learning
      disabilities were indistinguishable from children with mild learning disabilities
      on simple span tasks, but were significantly poorer than the mild group on the
      more demanding complex span tasks. For the group as a whole, working memory was
      strongly related to mental age.

PMID- 11594350
TI  - Contribution of lexico-semantic processes to verbal short-term memory tasks: a
      PET activation study.
AB  - Recent studies have demonstrated the intervention of long-term memory processes
      in verbal STM tasks and several cognitive models have been proposed to explain
      these effects. A PET study was performed in order to determine whether
      supplementary cerebral areas are involved when subjects have to execute short
      term memory tasks for items having representations in long-term memory (in
      comparison to items without such representations: words vs non-words). Results
      indicate that verbal STM for words specifically involves the left middle temporal
      gyrus (BA 21) and temporo-parietal junction (BA 39). These areas can be
      associated with lexical and semantic processes. These results are in agreement
      with cognitive models that postulate the simultaneous influence of lexical and
      semantic long-term representations on verbal STM processes and/or a lexico
      semantic buffer.

PMID- 11594351
TI  - Short-term retention of lexical-semantic representations: implications for speech
      production.
AB  - Patients with semantic STM deficits have difficulty comprehending sentences that
      require the retention of several lexical-semantic representations prior to their
      integration into higher-level propositions (Martin, 1995: Martin & Romani. 1994).
      In Experiment 1, patients with a semantic retention deficit had difficulty with
      the same type of constructions in speech production, namely noun phrases with one
      or two prenominal adjectives. Their performance improved when they could produce
      the nouns and adjectives in sentence form, which placed smaller demands on
      lexical-semantic retention. In Experiment 2 these patients were better able to
      produce syntactically complex sentences than the prenominal adjective phrases
      having an equal number of content words, indicating that the findings in
      Experiment 1 could not be attributed to syntactic complexity. These patients
      produced more pauses in the sentence constructions in Experiments 1 and 2,
      suggesting that the timing of such productions is abnormal. In contrast, patient
      EA, with a phonological retention deficit, performed better than the patients
      with a semantic retention deficit on the AN phrases despite having a smaller STM
      span. She showed no significant benefit of producing sentence compared to phrase
      constructions, and also made fewer and shorter pauses than the other patients.
      These findings support the multiple capacities view of verbal working memory and
      suggest that the same semantic retention capacity used in language comprehension
      is used in speech production.

PMID- 11594352
TI  - A re-evaluation of the phonological similarity effect in adults' short-term
      memory of words and nonwords.
AB  - The phonological similarity effect (PSE) was studied in two tasks of serial
      recall, in one task of serial recognition and one item identification task. PSE
      occurred only in the former three tasks involving memory of order when study
      items were words and nonwords with an associative connectedness to long-term
      memory. Nonwords that, according to a reaction time assessment of associative
      value, were less well connected to long-term memory mechanisms, were not
      sensitive to phonological similarity. These results are discussed in relation to
      contemporary models of short-term memory that explain the PSE as a result of
      confusions of items that are similarly encoded in a phonological layer. This
      layer is identified as a higher-level phonological space that is accessed by
      words and nonwords of high associative value and not by nonwords of low
      associative value.

PMID- 11594354
TI  - The phonological loop and memory for rhythms: an individual differences approach.
AB  - The purpose of the current study was to examine the relationship between short
      term memory for rhythm and the phonological loop in working memory. Results
      showed that digit span scores significantly correlated with the scores on the
      rhythmic memory task, and that the correlation between the two scores remained
      significant even after the common variance with reading speed was partialled out.
      Partial correlation and regression analyses indicated that the relation between
      memory for rhythm and digit span scores is mediated by the third component in the
      phonological loop, the component that is responsible for regulation of timing
      mechanisms in immediate memory tasks.

PMID- 11594353
TI  - Modelling serial position curves with temporal distinctiveness.
AB  - We offer a critique of the temporal distinctiveness model of serial position
      effects (Nairne, Neath, Serra, & Byun, 1997). The temporal distinctiveness model
      combines a precise definition of stimulus distinctiveness with a memory
      perturbation process. The critique is empirically motivated-we show that with a
      more complete analysis, the temporal distinctiveness model does not adequately
      account for Nairne et al.'s experimental data. To better account for the data, we
      independently modified two components of Nairne et al.'s model: the mathematical
      form of the definition of temporal distinctiveness and the mathematical form of
      the mapping from distinctiveness to free-recall probabilities. Both of these
      modifications provided for better fits. Yet both Nairne et al.'s definition and
      our modified definition are fairly arbitrary. We show that a significant
      challenge to this approach is to find theoretically motivated constraints of the
      temporal distinctiveness model while providing for adequate fits to data.

PMID- 11594355
TI  - The impact of broadband noise on serial memory: changes in band-pass frequency
      increase disruption.
AB  - Irrelevant sound consisting of bursts of broadband noise, in which centre
      frequency changes with each burst, markedly impaired short-term memory for order.
      In contrast, a sequence of irrelevant sound in which the same band-pass noise
      burst was repeated did not produce significant disruption. Serial recall for both
      visual-verbal (Experiment 1) and visual-spatial items (Experiment 2) was
      sensitive to the increased disruption produced by changing irrelevant noise. The
      results provide evidence that sounds that are largely aperiodic can produce
      marked disruption of serial recall in a similar manner to periodic sounds (e.g.,
      speech, musical streams, and tones), and thus show a changing-state effect.

PMID- 11594356
TI  - Word length and phonological similarity effects in simple, complex, and delayed
      serial recall tasks: implications for working memory.
AB  - Some current models of working memory argue that a passive short-term store is
      not involved in more dynamic working memory tasks. Other models argue that
      standard short-term memory and working memory tasks rely on common storage
      facilities. We examine these issues by exploring two signature effects of passive
      short-term storage in simple span, complex span, and Brown-Peterson tasks. The
      finding that all three tasks show word length and phonological similarity effects
      suggests that common processes or storage mechanisms are involved in all tasks.
      The implications for models of working memory are discussed.

PMID- 11594357
TI  - Phonological short-term memory contributions to sentence processing in young
      children.
AB  - Two experiments investigated the contribution of phonological short-term memory
      to the processing of spoken sentences by 4- and 5-year-old children. In
      Experiment 1, sentences contained either short or longer words, and varied in
      syntactic structure. Overall, repetition but not comprehension of the sentences
      was significantly influenced by word length. In Experiment 2. children selected
      on the basis of their high phonological short-term memory ability were founded to
      be superior at repeating sentences to children of lower phonological short-term
      memory ability, although the two groups did not differ in their comprehension
      accuracy for the same sentences. In both experiments, comprehension and
      repetition performance were differently influenced by particular sentence
      structures. It is proposed that sentence repetition in children is constrained by
      phonological memory capacity, and is therefore directly influenced by memory
      related factors that include the length and number of words in sentences, and
      individual differences in memory skills.

PMID- 11594358
TI  - Working memory and inferences: evidence from eye fixations during reading.
AB  - Eye fixations during reading were monitored to examine the relationship between
      individual differences in working memory capacity-as assessed by the reading span
      task-and inferences about predictable events. Context sentences predicting likely
      events, or non-predicting control sentences, were presented. They were followed
      by continuation sentences in which a target word represented an event to be
      inferred (inferential word) or an unlikely event (non-predictable word). A main
      effect of reading span showed that high working memory capacity was related to
      shorter gaze durations across sentence regions. More specific findings involved
      an interaction between context, target, and reading span on late processing
      measures and regions. Thus, for high- but not for low-span readers, the
      predicting condition, relative to the control condition, facilitated reanalysis
      of the continuation sentence that represented the inference concept. This effect
      was revealed by a reduction in regression-path reading time in the last region of
      the sentence, involving less time reading that region and fewer regressions from
      it. These results indicate that working memory facilitates elaborative inferences
      during reading, but that this occurs at late text-integration processes, rather
      than at early lexical-access processes.

PMID- 11594359
TI  - Short-term memory and working memory as indices of children's cognitive skills.
AB  - In the current literature, empirical and conceptual distinctions have been drawn
      between a more or less passive short-term memory (STM) system and a more dynamic
      working memory (WM) system. Distinct tasks have been developed to measure their
      capacity and research has generally shown that, for adults, WM, and not STM, is a
      reliable predictor of general cognitive ability. However, the locus of the
      differences between the tasks has received little attention. We present data from
      children concerning measures of matrices reasoning ability, reading, and
      numerical skill along with forward and backward order serial recall of WM, STM,
      and STM with articulatory suppression tasks. As indices of children's cognitive
      skills, STM and WM are shown to be rather similar in terms of memory per se.
      Neither the opportunity for rehearsal nor task complexity provides satisfactory
      explanations for differences between memory tests.

PMID- 11594360
TI  - Working memory in spelling: evidence from backward typing.
AB  - Theories of spelling (Margolin, 1984; Nolan & Caramazza, 1983) propose a working
      memory system for storing order and identity information of letters during the
      spelling process. Capacity limitations related to the use of such a graphemic
      buffer were explored. Participants had to type words backwards. Longer pauses
      between key presses were assumed to signal points at which graphemic buffer
      contents were refreshed. Five- and six-letter words were divided by a major pause
      into chunks of two and three letters, partly coinciding with syllables.
      Articulatory suppression had no effect on performance. Increasing the length of
      the stimuli to seven to eight letters resulted in major pauses occurring at
      syllable boundaries, and performance becoming vulnerable to articulatory
      suppression but not foot tapping. Forward typing resulted in a similar pause
      pattern. The results suggest that chunks of approximately three letters can be
      handled at any one time. For short words the task seems to rely on non
      phonological modes of coding, whereas longer words appear to require the use of a
      phonological code, possibly for keeping track of progress through the word.

PMID- 11594361
TI  - The development of visuo-spatial working memory.
AB  - Children's performance on tests of visuo-spatial working memory improves with
      age, although relatively little is known about why this happens. One explanation
      concerns the development of the ability to recode visually presented information
      into phonological form. This process appears to be used from around 8 years of
      age and is a major contributor to tasks in which stimuli can be verbally
      labelled. However, evidence suggests that phonological recoding cannot account
      for all of the age-related change in performance on visuo-spatial working memory
      tasks. In this review, four other mechanisms (knowledge, processing strategies,
      processing speed, and attentional capacity) are considered in terms of their
      contribution to children's visuo-spatial working memory development.

PMID- 11594362
TI  - The effects of eye and limb movements on working memory.
AB  - Three experiments examined the role of eye and limb movements in the maintenance
      of information in spatial working memory. In Experiment 1, reflexive saccades
      interfered with memory span for spatial locations but did not interfere with
      memory span for letters. In Experiment 2, three different types of eye movements
      (reflexive saccades, pro-saccades, and anti-saccades) interfered with working
      memory to the same extent. In all three cases, spatial working memory was much
      more affected than verbal working memory. The results of these two experiments
      suggest that eye movements interfere with spatial working memory primarily by
      disrupting processes localised in the visuospatial sketchpad. In Experiment 3,
      limb movements performed while maintaining fixation produced as much interference
      with spatial working memory as reflexive saccades. These results suggest that the
      interference produced by eye movements is not the result of their visual
      consequences. Rather, all spatially directed movements appear to have similar
      effects on visuospatial working memory.

PMID- 11594363
TI  - Field dependence-independence from a working memory perspective: a dual-task
      investigation of the Hidden Figures test.
AB  - Field dependence-independence (FDI) is a construct intensively investigated
      within cognitive style research, but its cognitive underpinnings are not clearly
      specified. We propose that performance on FDI tasks primarily reflects the
      operations of the visuospatial and executive components of working memory. We
      tested this hypothesis in a dual-task experiment with a commonly used measure of
      FDI, the Hidden Figures Test. The results showed that performance on this test
      was impaired by concurrent performance of secondary tasks that primarily tap the
      visuospatial component (spatial tapping) and the executive component (2-back and
      random number generation), but was almost unaffected by other secondary tasks
      (simple tapping and articulatory suppression). Moreover, an analysis of secondary
      task performance ruled out the possibility of strategic trade-offs and revealed
      an intriguing dissociation for two different sets of "randomness" indices for the
      random number generation task. These results support the hypothesised mapping
      between FDI and working memory components and suggest that the dual-task paradigm
      can provide a useful way to bring underspecified constructs like FDI into closer
      alignment with theoretical ideas developed within cognitive psychology.

PMID- 11594364
TI  - Low potassium enhances sodium uptake in red-beet under moderate saline
      conditions.
AB  - Due to the discrepancy in metabolic sodium (Na) requirements between plants and
      animals, cycling of Na between humans and plants is limited and critical to the
      proper functioning of bio-regenerative life support systems, being considered for
      long-term human habitats in space (e.g., Martian bases). This study was conducted
      to determine the effects of limited potassium (K) on growth, Na uptake,
      photosynthesis, ionic partitioning, and water relations of red-beet (Beta
      vulgaris L. ssp. vulgaris) under moderate Na-saline conditions. Two cultivars,
      Klein Bol, and Ruby Queen were grown for 42 days in a growth chamber using a re
      circulating nutrient film technique where the supplied K levels were 5.0, 1.25,
      0.25, and 0.10 mM in a modified half-strength Hoagland solution salinized with 50
      mM NaCl. Reducing K levels from 5.0 to 0.10 mM quadrupled the Na uptake, and
      lamina Na levels reached -20 g kg-1 dwt. Lamina K levels decreased from -60 g kg
      1 dwt at 5.0 mM K to -4.0 g kg-1 dwt at 0.10 mM K. Ruby Queen and Klein Bol
      responded differently to these changes in Na and K status. Klein Bol showed a
      linear decline in dry matter production with a decrease in available K, whereas
      for cv. Ruby Queen, growth was stimulated at 1.25 mM K and relatively insensitive
      to a further decreases of K down to 0.10 mM. Leaf glycinebetaine levels showed no
      significant response to the changing K treatments. Leaf relative water content
      and osmotic potential were significantly higher for both cultivars at low-K
      treatments. Leaf chlorophyll levels were significantly decreased at low-K
      treatments, but leaf photosynthetic rates showed no significant difference. No
      substantial changes were observed in the total cation concentration of plant
      tissues despite major shifts in the relative Na and K uptake at various K levels.
      Sodium accounted for 90% of the total cation uptake at the low K levels, and thus
      Na was likely replacing K in osmotic functions without negatively affecting the
      plant water status, or growth. Our results also suggest that cv. Ruby Queen can
      tolerate a much higher Na tissue concentration than cv. Klein Bol before there is
      any growth reduction. Grant numbers: 12180.

PMID- 11594365
TI  - Effect of volatile metabolites of dill, radish and garlic on growth of bacteria.
AB  - In a model experiment plants were grown in sealed chambers on expanded clay
      aggregate under the luminance of 150 W/m2 PAR and the temperature of 24 degrees
      C. Seven bacterial strains under investigation, replicated on nutrient medium
      surface in Petri dishes, were grown in the atmosphere of cultivated plants.
      Microbial response was evaluated by the difference between colony size in
      experiment and in control. In control, bacteria grew in the atmosphere of clean
      air. To study the effects of volatile metabolites of various plant on microbial
      growth, the experimental data were compared with the background values defined
      for each individual experiment. Expanded clay aggregate, luminance, temperature,
      and sealed chamber (without plants) for the background were the same. Volatile
      metabolites from 28-days old radish plants have been reliably established to have
      no effect on the growth of microbes under investigation. Metabolites of 30-days
      old dill and 50-days old garlic have been established to have reliable
      bacteriostatic effect on the growth of three bacterial strains. Dill and garlic
      have been found to have different range of effects of volatile substances on
      bacterial growth. Volatile metabolites of dill and garlic differed in their
      effect on the sensitivity spectrum of bacteria. An attempt has been made to
      describe the obtained data mathematically.

PMID- 11594366
TI  - Analysis of problematic time series with the Lomb-Scargle Method, a reply to
      'emphasizing difficulties in the detection of rhythms with Lomb-Scargle
      periodograms'.

PMID- 11594367
TI  - A brief response to Dr. Schimmel's reply.

PMID- 11594369
TI  - Graviperception and gravitaxis in algae.
AB  - Photosynthetic flagellates are among the most intensely studied unicellular
      organisms in the field of graviperception and gravitaxis. While the phenomenon of
      graviorientation has been known for many decades, only recently was the molecular
      mechanism unveiled. Earlier hypotheses tried to explain the precise orientation
      by a passive buoy mechanism assuming the tail end to be heavier than the front.
      In the photosynthetic flagellate Euglena gracilis, the whole cell body is denser
      than the surrounding medium, pressing onto the lower cell membrane where it seems
      to activate mechanosensitive ion channels specific for calcium. The calcium
      entering the cells during reorientation can be visualized by the fluorescence
      probe, Calcium Crimson. Cyclic AMP is likewise involved in the molecular pathway.
      Inhibitors of calcium channels and ionophores impair gravitaxis while caffeine, a
      blocker of the phosphodiesterase, enhances the precision of orientation.

PMID- 11594368
TI  - Gravitropism of axial organs in multicellular plants.
AB  - Gravitropism of plant organs such as roots, stems and coleoptiles can be
      separated into four distinct phases: 1. perception (gravity sensing), 2.
      transduction of a signal into the target region and 3. the response (differential
      growth). This last reaction is followed by a straightening of the curved organ
      (4.). The perception of the gravitropic stimulus upon horizontal positioning of
      the organ (1.) occurs via amyloplasts that sediment within the statocytes. This
      conclusion is supported by our finding that submerged rice coleoptiles that lack
      sedimentable amyloplasts show no graviresponse. The mode of signal transduction
      (2.) from the statocytes to the peripheral cell layers is still unknown.
      Differential growth (3.) consists of a cessation of cell expansion on the upper
      side and an enhancement of elongation on the lower side of the organ. Based on
      the facts that the sturdy outer epidermal wall (OEW) constitutes the growth
      controlling structure of the coleoptile and that growth-related osmiophilic
      particles accumulate on the upper OEW, it is concluded that the differential
      incorporation of wall material (presumably glycoproteins) is causally involved.
      During gravitropic bending, electron-dense particles ('wall-loosening capacity')
      accumulate on the growth-inhibited upper OEW. It is proposed that the autotropic
      straightening response, which is in part due to an acceleration of cell
      elongation on the curved upper side, may be attributable to an incorporation of
      the accumulated particles ('release of wall-loosening capacity'). This novel
      mechanism of autotropic re-bending and its implications for the Cholodny-Went
      hypothesis are discussed.

PMID- 11594370
TI  - Gravity sensing in moss protonemata.
AB  - Moss protonemata are a valuable system for studying gravitropism because both
      sensing and upward curvature (oriented tip growth) take place in the same cell.
      We review existing evidence, especially for Ceratodon purpureus, that addresses
      whether the mass that functions in sensing is that of amyloplasts that sediment.
      Recent experiments show that gravitropism can take place in media that are denser
      than the apical cell. This indicates that gravity sensing relies on an
      intracellular mass rather than that of the entire cell and provides further
      support for the starch-statolith hypothesis of sensing. Possible mechanisms for
      how amyloplast mass functions in sensing and transduction are discussed.

PMID- 11594371
TI  - Phototropism in Arabidopsis roots is mediated by two sensory systems.
AB  - Phototropism has been well-characterized in stems and stem-like organs, but there
      have been relatively few studies of root phototropism. Our experiments suggest
      that there are two photosensory systems that elicit phototropic responses in
      roots of Arabidopsis thaliana: a previously identified blue-light photoreceptor
      system mediated by phototropin (=NPH1 protein) and a novel red-light-based
      mechanism. The phototropic responses in roots are much weaker than the
      graviresponse, which competes with and often masks the phototropic response. It
      was through the use of mutant plants with a weakened graviresponse that we were
      able to identify the activity of the red-light-dependent phototropic system. In
      addition, the red-light-based photoresponse in roots is even weaker compared to
      the blue-light response. Our results also suggest that phytochrome may be
      involved in mediating positive phototropism in roots.

PMID- 11594372
TI  - Intracellular magnetophoresis of statoliths in Chara rhizoids and analysis of
      cytoplasm viscoelasticity.
AB  - The statoliths in Chara rhizoids are denser and more diamagnetic than the
      cytoplasm, therefore they can be displaced inside a living cell by a sufficiently
      strong high gradient magnetic field (HGMF). An experimental setup for
      intracellular magnetophoresis of statoliths was developed. The movement of
      statoliths and rhizoid growth was measured by video microscopy either under the
      influence of gravity or a HGMF equivalent to about 2 g. The contribution of the
      cytoskeleton to statolith motility was assayed before and after depolymerizing
      microtubules with oryzalin and F-actin with latrunculin B. Application of
      latrunculin caused immediate cessation of growth, clumping of statoliths, and
      application of HGMF resulted in higher displacement of statoliths. Oryzalin had
      no effect on the behavior of statoliths. The data indicate that magnetophoresis
      is a useful tool to study the gravisensing system and rheology of the Chara
      rhizoid.

PMID- 11594373
TI  - Paramecium--a model system for studying cellular graviperception.
AB  - Experiments under varied gravitational accelerations as well as in density
      adjusted media showed that sensation of gravity in protists may be linked to the
      known principles of mechanosensation. Paramecium, a ciliate with clear
      graviresponses (gravitaxis and gravikinesis) is an ideal model system to prove
      this hypothesis since the ciliary activity and thus the swimming behaviour is
      controlled by the membrane potential. It has also been assumed that the
      cytoplasmic mass causes a distinct stimulation of the bipolarly distributed
      mechano-sensitive K+ and Ca2+ ion channels in the plasma membrane in dependence
      of the spatial orientation of the cell. In order to prove this hypothesis,
      different channel blockers are currently under investigation. Gadolinium did not
      inhibit gravitaxis in Paramecium, showing that it does not specifically block
      gravireceptors. Further studies concentrated on the question of whether second
      messengers are involved in the gravity signal transduction chain. Exposure to 5 g
      for up to 10 min led to a significant increase in cAMP.

PMID- 11594374
TI  - Force sensitivity of plant gravisensing.
AB  - Rotation at 4, 10, 50 and 100 rpm on a horizontal clinostat and in microgravity
      exerts limited effects on the morphogenesis of lettuce and cress root statocytes
      and statoliths if compared with the vertical control or 1 g spaceflight reference
      centrifuge. However, the average distance of statoliths from the distal wall
      increases. The pattern of plastid location of microgravity-grown and that of
      clino-rotated samples has been determined at 10, 50, and 100 rpm. Experiments on
      the centrifuge-clinostat and spaceflight centrifuge (acceleration forces of 0.005
      to 1 g) revealed that the average statolith location depends on the amplitude of
      acropetally or basipetally directed mass acceleration. Decreasing the acropetally
      directed force from 1 g to 0.4 g dislocates statoliths towards the cell center
      possibly mediated by the elastic forces of the cytoskeleton. In statocytes formed
      on the clinostat or in microgravity, the majority of statoliths are located at
      the center of the cell. To force the statoliths from the center of the statocyte
      towards one of its poles, a threshold mass acceleration of 0.01 g is required.
      Statocytes with centrally-located statoliths are considerably more effective in
      transducing a gravistimulus than those with distally-located plastids. The latent
      time of the graviresponse is shorter and the response itself is enhanced in roots
      grown on the clinostat compared to vertically grown samples. The early phases of
      graviperception are independent of root growth conditions since presentation time
      and g-threshold are similar for roots grown stationary and those on a clinostat.
      We propose a sequence of events in gravitropic stimulation that considers not
      only the lateral displacement of statoliths, as predicted by the starch-statolith
      hypothesis, but also its longitudinal motion, together with differential
      gravisensitivity of mechanotransducing structures along the lower-most
      longitudinal cell wall.

PMID- 11594375
TI  - Theoretical considerations of plant gravisensing.
AB  - The mechanisms proposed to explain gravity sensing can be divided into two
      groups, "statolith" and "non-statolith" mechanisms. The traditional estimates of
      the plausibility of these mechanisms are based on the analysis of the signal-to
      noise ratio. The existing data indicate that the problem of plant gravisensing
      may be related to the general problem of the detection of weak signals in
      mechanoreceptors. This paper reviews the known mechanisms of plant gravisensing
      as well as the latest nonlinear stochastic models of mechanoreception in which
      noise promotes detection and amplification of weak signals. These models based on
      nonlinear stochastic phenomena may be used to explain plant gravisensing, if the
      cell is considered a dynamic, spatially distributed system of active
      intracellular cytoskeletal networks and mechanosensitive proteins.

PMID- 11594376
TI  - Autonomic straightening of gravitropically curved cress roots in microgravity.
AB  - The typical response of plant organs to gravistimulation is differential growth
      that leads to organ bending. If the gravitropic stimulus is withdrawn, endogenous
      compensation of the graviresponse and subsequent straightening occur in some
      plants. For instance, autonomic straightening of Lepidium roots occurs when
      gravitropically-curved rootsare rotated on a clinostat (Stankovi et al., 1998a).
      To determine whether endogenous compensation of the graviresponse also occurs in
      space, microgravity-grown cress roots were laterally centrifuged in-flight and
      then returned to microgravity using Biorack hardware on a shuttle mission (STS
      81). The cress roots were centrifuged at 4 different g-doses (0.1 x g and 1 x g
      for 15 or 75 min). All four treatments yielded varying degrees of root curvature.
      Upon removal from the centrifuge, roots in all four treatments underwent
      subsequent straightening in microgravity. This straightening resulted from a loss
      of gravitropic curvature in older regions of the root and the coordinated
      alignment of new growth. These results show that both microgravity and clinostat
      rotation on Earth are equivalent in stimulus withdrawal with respect to the
      induction of endogenous compensation of the curvature. Cress roots are the only
      plant organ shown to undergo compensation of the curvature in both microgravity
      and on a clinostat. The compensation of graviresponse in space rules out the
      hypothesis that the endogenous root straightening ("autotropism") represents a
      commitment to a pre-stimulus orientation with respect to gravity and instead
      suggests that there is a default tendency towards axiality following a withdrawal
      of a g-stimulus.

PMID- 11594377
TI  - Robotic steps may help spinal cord patients.

PMID- 11594379
TI  - Suspected adverse reactions, 2000.

PMID- 11594378
TI  - Reverse osmosis filtration for space mission wastewater: membrane properties and
      operating conditions.
AB  - Reverse osmosis (RO) is a compact process that has potential for the removal of
      ionic and organic pollutants for recycling space mission wastewater. Seven
      candidate RO membranes were compared using a batch stirred cell to determine the
      membrane flux and the solute rejection for synthetic space mission wastewaters.
      Even though the urea molecule is larger than ions such as Na+, Cl-, and NH4+, the
      rejection of urea is lower. This indicates that the chemical interaction between
      solutes and the membrane is more important than the size exclusion effect. Low
      pressure reverse osmosis (LPRO) membranes appear to be most desirable because of
      their high permeate flux and rejection. Solute rejection is dependent on the
      shear rate, indicating the importance of concentration polarization. A simple
      transport model based on the solution-diffusion model incorporating concentration
      polarization is used to interpret the experimental results and predict rejection
      over a range of operating conditions. Grant numbers: NAG 9-1053.

PMID- 11594380
TI  - PrP genotype frequencies in German breeding sheep and the potential to breed for
      resistance to scrapie.
AB  - Genetic susceptibility to scrapie is associated with polymorphisms in three
      different codons of the ovine prion protein (PrP) gene (136, 154, 171). Studies
      of PrP genotypes linked to scrapie have revealed the resistance of homozygous
      PrPARR/PrPARR animals and the high risk of PrPVRQ/PrPVRQ and PrPvRQ/PrPARQ
      animals in scrapie-affected flocks. The selection of PrPARR/PrPARR genotypes may
      therefore provide a strategy for controlling clinical scrapie. The genotypes of
      1361 German breeding sheep from 15 different breeds in northern Germany were
      determined. Apart from the wildtype allele PrPARQ, at least four mutually
      exclusive allelic variants were found. The greatest variability within the PrP
      gene was encountered in texel sheep, in which 14 PrP genotypes were found. In the
      important meat breeds, Suffolk, German whiteheaded mutton and German blackheaded
      mutton, the PrPARR allele was predominant, and in these breeds the breeding of
      scrapie-resistant pedigree flocks within four generations seems to be a feasible
      option. In the texel sheep, the German merino, the German milk and the German
      land sheep breeds, the frequency of the PrPARR allele was much lower, and in
      several breeds no homozygous rams were available for breeding purposes. In these
      breeds the breeding strategy would depend on the number of heterozygous rams
      available, but resistant pedigree flocks could be achieved within nine
      generations.

PMID- 11594381
TI  - Avulsion of the tibial tuberosity with separation of the proximal tibial physis
      in seven dogs.
AB  - Seven dogs developed avulsions of the tibial tuberosity apophysis in combination
      with a fracture of the proximal tibial physis. Six of them were small terrier
      breeds, treated by internal fixation using two Kirschner wires and a tension band
      in five cases, and crossed Kirschner wires alone in the other. The seventh case
      was managed conservatively. The tension band repair was simple, provided adeqate
      fixation and avoided the placement of implants across the proximal tibial physis.

PMID- 11594382
TI  - Clinical and pathological observations on pigs with postweaning multisystemic
      wasting syndrome.
AB  - The aim of this work was to characterise the lesions and agents present in
      clinically normal and clinically affected pigs on a farm during an outbreak of
      postweaning multisystemic wasting syndrome (PMWS), and to evaluate the diagnostic
      techniques for detecting porcine circovirus type 2 (PCV-2) and other
      microorganisms. Four pigs in the early stage and 11 pigs in the late stage of the
      disease, and eight clinically normal pigs were necropsied. Samples of lymphoid
      tissue and serum were also obtained from 12 slaughter pigs from the same farm.
      The tissues were examined histopathologically, and in situ hybridisation,
      serology and PCR were used to detect porcine circovirus type 1 (PCV-1) and/or PCV
      2 in tissues and/or sera. The presence of porcine reproductive and respiratory
      syndrome virus (PRRSV), Aujeszky's disease virus (ADV) and porcine parvovirus
      (PPV) were also investigated. Characteristic microscopical lesions of PMWS were
      observed in the lymphoid tissues of the pigs in all three necropsied groups; the
      lesions were most common and severe in the pigs in the early stage of the
      disease, less so in the pigs in the late stage of the disease, and least in the
      clinically normal pigs. PCV-2 infection was detected in all the necropsied pigs
      by in situ hybridisation and PCR. Only three pigs had the PCV-1 genome in serum
      or lymph node tissue. In contrast, the slaughter pigs had no microscopical
      lesions and no PCV-2 nucleic acid in their serum or tissues, and only one of them
      had the pCV-1 genome in its serum. Immunohistochemical, serological and PCR
      studies revealed that PRRSV and ADV were also present on the farm during the
      outbreak.

PMID- 11594383
TI  - Ovulated pig oocyte production using transcutaneous ultrasonography to determine
      ovulation time.

PMID- 11594384
TI  - Acquired pelvic nerve dysfunction associated with impotence and urinary
      incontinence in a Limousin bull.

PMID- 11594385
TI  - Evidence of bovine non-group A rotavirus in diarrhoeic neonatal calves in India.

PMID- 11594386
TI  - EU requirement to survey for BSE in fallen stock: consequences for postmortem
      examination.

PMID- 11594387
TI  - Training in international animal health.

PMID- 11594388
TI  - Ethical decision-making in veterinary practice.

PMID- 11594389
TI  - Euthanasia of greyhounds.

PMID- 11594390
TI  - Evaluation and application of liquid chromatographic columns coated with
      'intelligent' ligands: (I) acylcarnitine column.
AB  - Unique stationary phases of octadecylsilica (ODS) coated with acylcarnitines have
      been developed for liquid chromatographic columns. The ODS column coated with
      acylcarnitine was readily prepared by recycling the solution containing
      acylcarnitine through an ODS column in a closed loop. Acylcarnitine was adsorbed
      on the ODS surfaces by hydrophobic interaction between the acyl group of
      acylcarnitine and the octadecyl group of the ODS phases. The ODS column coated
      with stearoylcarnitine (CN-18 column) was the most stable among the four columns
      coated with acylcarnitines of various acyl chain lengths (decanoylcarnitine,
      lauroylcarnitine, myristoylcarnitine, and stearoylcarnitine) under the condition
      of delivery of the mobile phase, indicating that adsorption of acylcarnitine on
      the ODS surfaces depended on the length of acyl chains. The CN-18 column was
      usable for delivering the mobile phase contained less than 20% (v/v)
      acetonitrile, retaining almost the same separation efficiency as the intact ODS
      column. The retention behavior of ionic solutes on the CN-18 column could be
      explained by both ionic and electrostatic interactions between the solutes and
      the stationary phase. The CN-18 column enabled efficient separation of inorganic
      anions, nicotinic acids, amino acids, and nucleotides. The chiral ODS column
      coated with enantiomer of stearoylcarnitine, L-stearoylcarnitine (L-CN-18 column)
      could achieve direct enantiomeric separation of DL-tryptophan, alpha-methyl-DL
      tryptophan and DL-3-indolelactic acid using 100% water as the mobile phase. The L
      CN-18 column could also separate enantiomers of amino acids and alpha
      hydroxycarboxylic acids by ligand-exchange chromatographic mode using a mobile
      phase containing copper(II) ion. The chiral recognition is discussed for
      enantiomeric separation on the L-CN-18 column.

PMID- 11594391
TI  - Chiral supercritical fluid chromatography on porous graphitic carbon using
      commercial dimethyl beta-cyclodextrins as mobile phase additive.
AB  - Using dimethylated-beta-cyclodextrin mixtures (MeCD) as chiral selectors in CO2
      polar modifier mobile phase and porous graphitic carbon as solid-phase, chiral
      supercritical (or subcritical) fluid chromatography was performed. The adsorbed
      quantity of MeCD onto the porous graphitic carbon (Hypercarb) was measured for
      various chiral selector concentrations using the breakthrough method with
      evaporative light scattering detector. The effects of MeCD concentration in the
      mobile phase, the nature of the polar modifier, the outlet pressure, the column
      temperature and the nature of the commercial MeCD mixture on the retention and
      the enantioselectivities were studied. For a given solute, the enantioselectivity
      is greatly dependent on the commercial MeCD mixture used. The retention mechanism
      was also studied. From the data, we find that the dominant mechanism for the
      chiral discrimination is the diastereoisomeric complexation in the mobile phase.

PMID- 11594392
TI  - Salt effects in capillary zone electrophoresis. V. Adsorption and retention of
      electrically neutral analytes.
AB  - Two electrically neutral analytes previously observed to be separated from the
      neutral marker in capillary zone electrophoresis (CZE) experiments
      [sulphanilamide (SAA) and sulphaguanidine (SGW)] have been examined to determine
      the basis for separation. The degree of separation increases markedly with buffer
      concentration and improves with increasing field strength. On the basis of the
      apparent electrophoretic mobilities in conventional CZE, migration times in a
      zero EOF environment were calculated for SAA, SGW and six other sulphonamides
      that were known to be ionized. These six markers were used to test the legitimacy
      of our predictions and to correct for small discrepancies between the predicted
      and observed migration times. It was concluded that SAA and SGW have negligible
      electrophoretic mobilities and that they are retained in the electrical double
      layer close to the capillary wall. A mechanism for adsorption is proposed and the
      generality of the phenomenon is discussed.

PMID- 11594393
TI  - Characterisation of electroosmotic flow in capillary electrochromatography
      columns.
AB  - Currently available capillary electrochromatography (CEC) instrumentation using
      UV-Vis detection dictates the use of duplex columns. Due to discontinuities
      (electric field strength and conductivity) that arise at the boundary between the
      packed and open sections in these columns, the determination of the
      electroosmotic flow (EOF) is complicated. Thiourea has been found to be an
      accurate EOF marker under the conditions employed in this study. By injecting
      this compound onto a fully packed column and comparing the obtained mobilities
      with those calculated from measured zeta potential values a value for tortuosity
      has been obtained. The use of laser Doppler velocimetry (LDV) for the measurement
      of zeta potential has been found to be the most direct and rapid method of
      characterising silica support materials in terms of electroosmotic mobility. The
      open section in duplex CEC columns has been shown to influence the actual column
      flow-rate. The EOF measured using duplex columns of varying packed and open
      section lengths have been compared with those obtained for a fully packed column.

PMID- 11594394
TI  - Liquid chromatographic determination of total and beta-N-oxalyl-L-alpha,beta
      diaminopropionic acid in lathyrus sativus seeds using both refractive index and
      bioelectrochemical detection.
AB  - A further improved chromatographic method for the simultaneous determination of
      the total amount of ODAP, selectively the amount of its neurotoxic form, beta
      ODAP, and free L-glutamate in raw Lathyrus sativus (grass pea) seed samples is
      described using post-column refractive index in combination with
      bioelectrochemical detection. The biosensor is based on crosslinking horseradish
      peroxidase (HRP) and an Os-containing mediating polymer with
      poly(ethyleneglycol)(400) diglycidyl ether (PEGDGE), forming an inner hydrogel
      layer and then immobilising L-glutamate oxidase (GlOx) as an outer layer on top
      of a graphite electrode. Addition of polyethylenimine (PEI) to the hydrogel is
      believed to have sensitivity and stability enhancing effect on the biosensor. The
      double-layer approach in the biosensor construction avoided direct electrical
      wiring of GlOx and resulted in a higher sensitivity of 4.6 mA/M cm2 with respect
      to beta-ODAP and a wider linear range (1-250 microM) for both L-glutamate and
      beta-ODAP when compared with a single-layer approach where GlOx, HRP, and Os
      polymer are crosslinked together. The limit of detection for the chromatographic
      biosensor system was found to be 2 microM with respect to beta-ODAP and 0.7
      microM with respect to L-glutamate. The refractive index detection on-line with
      the biosensor enabled full control of the chromatographic system for the
      determination of the total amount of ODAP, selectively the amount of beta-ODAP
      and L-glutamate. Ten grass pea samples have been collected from Lathyrism prone
      areas of Ethiopia to test the applicability of the presently developed analytical
      system for real sample analysis. The toxin levels of grass pea collections were
      determined in an aqueous extracts and ranged from 0.52 to 0.76%, dry mass basis.
      Comparison of results of an established spectrophotometric assay and that of the
      present system has shown an extraordinary degree of agreement as revealed by
      parallel "t" test (90% confidence limit). The present system has operational
      stability of more than 50 h. Analysis time per sample is 10 min after extraction
      for 90 min.

PMID- 11594395
TI  - Simultaneous determination of ingredients in an ointment by hydrophobic
      interaction electrokinetic chromatography.
AB  - Hydrophobic interaction electrokinetic chromatography was used to simultaneously
      determine seven active ingredients (diphenhydramine hydrochloride, dibucaine
      hydrochloride, chlorhexidine hydrochloride, phenylephrine hydrochloride,
      hydrocortisone acetate, allantoin and tocopherol acetate) in an ointment. Not
      only hydrophobic but also ionic compounds were successfully separated by use of a
      separation solution composed of acetonitrile-water (80:20, v/v),
      tetradecylammonium salt and ammonium chloride. The migration behavior of the
      hydrophobic compound depended on tetradecylammonium concentration, while that of
      the ionic compounds depended on ammonium chloride concentration. An addition of
      triethylamine to the separation solution markedly improved the reproducibility of
      the peak areas of cations with a relative standard deviation (RSD) of less than
      1.7% (n=6). The established method was validated and confirmed to be applicable
      to the determination of the active ingredients in a commercial ointment. Sample
      preparation was performed by liquid-liquid extraction and no interference from
      the formulation excipients was observed. Good linearities were obtained, with
      correlation coefficients above 0.999. Recoveries and precisions ranged from 98.0
      to 100.8%, and from 0.4 to 2.9% RSD, respectively. These results suggest that
      hydrophobic interaction electrokinetic chromatography can be used for the
      determination of ionic compounds as well as hydrophobic compounds in ointment.

PMID- 11594396
TI  - Analysis of linear alkylbenzenesulfonates by capillary zone electrophoresis with
      large-volume sample stacking.
AB  - A systematic investigation of optimal conditions for determining the homologues
      of linear alkylbenzenesulfonates (LAS) by capillary zone electrophoresis (CZE)
      using the large-volume sample stacking technique was presented. The most
      effective sample stacking and separation conditions was 20 mM borate buffer with
      30% acetonitrile at pH 9.0, and the sample hydrodynamic injection of up to 90 s
      at 4 p.s.i. (1 p.s.i. = 6,892.86 Pa) (around 711 nl). Under such conditions,
      approximately a 100-fold enrichment factor was achieved based on peak heights.
      The reproducibility of migration time and quantitative results of stacking CZE
      can be improved by using internal standards. Quantitation limits of the
      homologues of LAS were 0.002-0.01 mg/l under these enrichment conditions. The
      analysis of real samples of laundry and dishwashing detergents was performed. The
      established high-performance liquid chromatography method was applied to evaluate
      the stacking CZE method, and compatible results were obtained.

PMID- 11594397
TI  - Routine o-glycan characterization in nutritional supplements--a comparison of
      analytical methods for the monitoring of the bovine kappa-casein macropeptide
      glycosylation.
AB  - Analytical procedures, including capillary isoelectric focusing (CIEF), high
      performance anion-exchange chromatography coupled to amperometric detection
      (HPAEC-PAD) and normal-phase chromatography with fluorescence detection are
      presented for the characterization of a highly O-glycosylated caseinomacropeptide
      (CGMP) and the detection of subtle glycosylation differences between CGMP Batches
      obtained with two different preparation procedures. Modified two-step CIEF
      allowed monitoring of glycopeptide heterogeneity and determination of the
      isoelectric points of acidic glycoforms. The mixture of wide and narrow pH range
      ampholytes was optimized to improve glycoform resolution. The pI of the different
      CGMP glycoforms was evaluated with pI internal standards and found to range
      between 3.08 and 3.58, which indicates a very acidic glycopeptide. Moreover, the
      monosaccharide composition was determined with HPAEC-PAD after neutral and amino
      sugars release by using adequate acidic hydrolysis of CGMP. Results indicated a
      similar composition for Batches I and II, but the monosaccharide percentages were
      3-4 fold higher in Batch I, particularly for galactose and glucose. This likely
      reflects a higher content in lactose in the case of Batch I. Finally, O-linked
      oligosaccharides were released with an automated hydrazinolysis and derivatized
      with a sensitive labelling reagent, 2-aminobenzamide. The derivatives were then
      analyzed by normal-phase HPLC coupled with fluorescence detection, and separated
      on the basis of hydrophilic interaction, which allowed oligosaccharide mapping of
      the two CGMP. It appeared that the two CGMP preparations had an almost identical
      O-glycan population, but CGMP Batch I was more glycosylated than Batch II.
      Additionally, the sizes of the separated glycans, expressed as the number of
      glucose units, were tentatively assigned using calibration with a partial
      hydrolysate of dextran. In conclusion, a combination of electrophoretic and
      chromatographic techniques was found powerful in studying glycoprotein
      heterogeneity and assessing batch-to-batch consistency.

PMID- 11594398
TI  - Procedure for the quantification of rider peaks.
AB  - Rider peaks are small peaks which are not well resolved from a large and
      asymmetrical neighbour but sit on its trailing side. The usual case is a large,
      tailed peak which is eluted just in front of the small peak, although the
      opposite situation can also occur (a small peak in front of a large peak with
      fronting). The common integration techniques. i.e. separating the peaks by
      vertical drop or by a tangent and determining area or height, give erroneous
      results. We propose a method for their quantification with low error. It is
      necessary to set up a "two-dimensional" calibration by varying both
      concentrations, i.e. of the large peak and of the rider. This leads to a series
      of linear equations which describe the rider size, as found by the integrator, as
      a function of the size of the large peak. The y-axis intercepts i of these
      equations show a linear relationship with the concentration x of the rider
      analyte, whereas the slopes s follow a quadratic relationship. These equations
      can be used to solve the equation y = s(x) x z + i(x) for x (y and z are the
      integrated peak size of the rider and the large peak, respectively). The
      procedure was tested with computer-generated peak pairs as well as with HPLC
      separations of 2,3-dimethylaniline (large tailing peak) and 2,3-dimethylphenol
      (symmetrical rider peak).

PMID- 11594399
TI  - Application of analytical and preparative high-speed counter-current
      chromatography for separation of lycopene from crude extract of tomato paste.
AB  - Lycopene was isolated from 100 mg of crude extract of tomato paste containing
      about 9% of lycopene. Analytical high-speed counter-current chromatography
      (HSCCC) was first used for the systematic selection of the two-phase solvent
      system. Then preparative HSCCC separation was performed with a nonaqueous solvent
      system composed of n-hexane-dichloromethane-acetonitrile at an optimum volume
      ratio of 10:3.5:6.5. This yielded 8.6 mg of lycopene at over 98.5% purity as
      determined by HPLC analysis.

PMID- 11594401
TI  - Quantititative determination of glycosylated and aglycon isoprenoid cytokinins at
      sub-picomolar levels by microcolumn liquid chromatography combined with
      electrospray tandem mass spectrometry.
AB  - Microcolumn liquid chromatography (microLC) combined with electrospray tandem
      mass spectrometry is used for the determination of intact glycosylated cytokinins
      and the corresponding aglycons at picomole and sub-picomole levels in plant
      tissue. Routine analysis was done on C8-bonded silica using a methanol-water
      gradient. Data acquisition was performed by multiple reaction monitoring.
      Quantification was carried out by using isotopically labelled analogues and
      applying linear regression to the response factor versus concentration data. For
      routine analysis a calibration range from 0.5 to 10 pmole injected on-column was
      used. The limits of detection ranged from 50 to 100 fmole injected on-column. The
      microLC procedure was used to analyse plant tissue extracts from transgenic
      homozygote and hemizygote as well as wild-type Nicotiana tabacum species, and
      cauliflower samples. The data were compared with results obtained by conventional
      immunoassay and a satisfactory correlation was found. Validation data are
      presented.

PMID- 11594400
TI  - Separation of endo-polygalacturonase using aqueous two-phase partitioning.
AB  - The partitioning of endo-polygalacturonase (endo-PG) in polyethylene glycol (PEG)
      polyvinyl alcohol (PVA10000) and PEG-hydroxypropyl starch (Reppal PES100) aqueous
      two-phase systems was studied, and revealed the possibility of using aqueous two
      phase extraction to purify and concentrate endo-PG from its clarified
      fermentation broth. For the PEG8000-PVA10000 system, endo-PG presented in the
      fermentation broth (at concentration that is more than 40% of total protein)
      mainly dominates in the top phase with a partitioning coefficient of 6, while
      total protein concentrates in the bottom phase. A separation scheme consisting of
      two consecutive aqueous two-phase extraction steps was proposed: a first
      extraction in polyethylene glycol (PEG8000)-polyvinyl alcohol system, followed by
      a second extraction in PEG8000-(NH4)2SO4 system. This allowed the separation of
      endo-PG from polymer and the recycling of PEG polymer, since endo-PG was very
      strongly partitioned into the bottom phase of the PEG8000-(NH4)2SO4 system.
      Laboratory-scale experiments were performed to test the efficiency of this
      scheme. It was found that enzyme recovery was up to 91% with a total purification
      factor of about 1.9 and a concentration factor of more than 5. About 90% of the
      total PEG added into the systems can be recovered, and no reduction was obtained
      in the purification factor using recycled PEG.

PMID- 11594402
TI  - Determination of paralytic shellfish poisoning toxins by high-performance ion
      exchange chromatography.
AB  - An efficient LC method has been developed for the determination of paralytic
      shellfish poisoning (PSP) toxins based on ion-exchange chromatographic separation
      of the toxins followed by electrochemical post-column oxidation and fluorescence
      detection as well as mass spectrometric (MS) detection. The method can be applied
      to the determination of PSP toxins in phytoplankton and to control seafood for
      PSP content.

PMID- 11594403
TI  - Radiosterilization of cefotaxime: investigation of potential degradation
      compounds by liquid chromatography-electrospray mass spectrometry.
AB  - The nonvolatile radiolytic compounds produced by irradiation of cefotaxime were
      studied by a liquid chromatography-electrospray mass spectrometry method. Full
      scan LC-MS was first performed in order to obtain the m/z value of the protonated
      molecules of all detected peaks. LC-MS-MS was then carried out on the compounds
      of interest. A comparison between the MS-MS spectrum of cefotaxime and those of
      the radiolytic compounds showed that their fragmentation patterns were very
      similar suggesting that they were structural analogues of the main drug. The
      examination of the two main fragmentation pathways also permitted the location of
      the modified substructures. Moreover, it was shown that some stereoisomers
      appeared with the irradiation process. The complete fragmentation pattern of
      cefotaxime was studied by MSn and used to obtain information about the structure
      of the radiolytic compounds. A complete structure was proposed for four of these.

PMID- 11594404
TI  - Screening and identification of unknown contaminants in water with liquid
      chromatography and quadrupole-orthogonal acceleration-time-of-flight tandem mass
      spectrometry.
AB  - In order to assess and maintain the quality of surface waters, target compound
      monitoring is often not sufficient. Many unknown micro-contaminants are present
      in water, originating in municipal, industrial or agricultural effluents. Some of
      these might pose a risk to drinking water production and consequently to human
      health. The possibilities of screening surface water and identification of these
      non-target water pollutants with modern data acquisition possibilities of hybrid
      quadrupole-orthogonal acceleration time of flight mass spectrometers (Q-TOF),
      such as data-dependent MS to MS/MS switching were investigated. Using model
      compounds, a procedure for the liquid chromatography-tandem mass spectrometry (LC
      MS/MS) screening of water extracts was developed, enabling the detection and
      identification of compounds at levels < or = 0.25 microg/l in surface water.
      Based on the accurate mass the elemental compositions for the precursor and
      product ions are calculated. The calculated chemical formulae are searched
      against the Merck index, the NIST library, an own database containing about 2,500
      water pollutants (pesticides and other contaminants) as well as a CI-CID library
      containing tandem MS spectra of about 100 water contaminants. The developed
      approach was applied for the identification of unknown compounds, present in
      native surface water extract. For three of these compounds, structures were
      proposed. Confirmation of the proposed structures with standards was beyond the
      scope of this study.

PMID- 11594405
TI  - Fast methods for screening of trichothecenes in fungal cultures using gas
      chromatography-tandem mass spectrometry.
AB  - The paper presents a fast method for trichothecene profiling and chemotaxonomic
      studies in species of Fusarium, Stachybotrys. Trichoderma and Memnoniella. Micro
      scale extracted crude Fusarium extracts were derivatised using
      pentafluoropropionic anhydride and analysed by gas chromatography with
      simultaneous full scan and tandem mass spectrometric detection. It was possible
      to monitor for up to four compounds simultaneous, making detection of acetyl T-2
      toxin, T-2 toxin, HT-2 toxin, T-2 triol. T-2 tetraol, neosolaniol, iso
      neosolaniol, scirpentriol, 4,15-diacetoxyscirpenol, 15-acetoxyscirpenol, 4
      acetoxyscirpentriol, nivalenol, fusarenon-X, deoxynivalenol, 15-acetyl
      deoxynivalenol and 3-acetyldeoxynivalenol possible during a 23-min GC run. A
      slightly modified method could detect trichothecenes produced by Stachybotrys,
      Memnoniella and Trichoderma, by hydrolysing crude extracts prior to
      derivatisation with heptafluorobuturyl imidazole. All types of derivatised
      extracts could be reanalysed using negative ion chemical ionisation (NICI) GC-MS
      for molecular mass determination and verification purposes. A retention time
      index could be used for correction in retention time drifts between sequences and
      worked both in EI+ and NICI mode.

PMID- 11594406
TI  - Ozone reaction with n-aldehydes (n=4-10), benzaldehyde, ethanol, isopropanol, and
      n-propanol adsorbed on a dual-bed graphitized carbon-carbon molecular sieve
      adsorbent cartridge.
AB  - Ozone reacts with n-aldehydes (n=4-10), benzaldehyde, ethanol, isopropanol and n
      propanol adsorbed on a dual-bed graphitized carbon-carbon molecular sieve
      adsorbent cartridge. Destruction of n-aldehydes increases with n number and with
      ozone concentration. In some sampling experiments both generation and destruction
      of n-aldehydes by ozone are observed. In field experiments the results of sample
      analysis for n-aldehydes and benzaldehyde are frequently not proportional to
      sample volume whereas results for toluene and isoprene, and sometimes for total
      carbon, are. A simple theory is developed to simulate the net result of three
      processes: the adsorption of compounds from an air stream onto a solid adsorbent,
      the generation of compounds by reaction of ozone with materials upstream of or on
      the adsorbent, and the destruction by ozone of pre-existing compounds and
      compounds adsorbed from the sample stream. The use of distributed volume pairs is
      recommended as a way to identify loss of sample integrity during air monitoring
      experiments.

PMID- 11594408
TI  - What is high-sensitivity C-reactive protein?

PMID- 11594407
TI  - Long-term efficacy and safety of cerivastatin 0.8 mg in patients with primary
      hypercholesterolemia.
AB  - BACKGROUND: Statins are the agents of choice in reducing elevated plasma low
      density lipoprotein cholesterol (LDL-C). HYPOTHESIS: Cerivastatin 0.8 mg has
      greater long-term efficacy in reducing LDL-C than pravastatin 40 mg in primary
      hypercholesterolemia. METHODS: In this double-blind, parallel-group, 52-week
      study, patients (n = 1,170) were randomized (4:1:1) to cerivastatin 0.8 mg,
      cerivastatin 0.4 mg, or placebo daily. After 8 weeks, placebo was switched to
      pravastatin 40 mg. Patients with insufficient LDL-C lowering after 24 weeks were
      allowed open-labeled resin therapy. RESULTS: Cerivastatin 0.8 mg reduced LDL-C
      versus cerivastatin 0.4 mg (40.8 vs. 33.6%, p <0.0001) or pravastatin 40 mg
      (31.5%, p<0.0001), and brought 81.8% of all patients, and 54.1% of patients with
      atherosclerotic disease, to National Cholesterol Education Program (NCEP) goals.
      Cerivastatin 0.8 mg improved mean total C (-29.0%), triglycerides (-18.3%), and
      high-density lipoprotein cholesterol (HDL-C) (+9.7%) (all p < or = 0.013 vs.
      pravastatin 40 mg). Higher baseline triglycerides were associated with greater
      reductions in triglycerides and elevations in HDL-C with cerivastatin.
      Cerivastatin was well tolerated; the most commonly reported adverse events were
      arthralgia, headache, pharyngitis, and rhinitis. Symptomatic creatine kinase >
      10x the upper limit of normal (ULN) occurred in 1, 1.5, and 0% of patients
      receiving cerivastatin 0.8 mg, cerivastatin 0.4 mg, and pravastatin 40 mg,
      respectively. Repeat hepatic transaminases >3 x ULN occurred in 0.3-0.5, 0.5, and
      0% of patients, respectively. CONCLUSION: In long-term use, cerivastatin 0.8 mg
      effectively and safely brings the majority of patients to NCEP goal.

PMID- 11594409
TI  - Assessment of subclinical atherosclerosis and cardiovascular risk.
AB  - Conventional cardiac risk factors do not fully explain the incidence of coronary
      artery disease and coronary events. Risk stratification and therapy based solely
      on these conventional risk factors may exclude a population who would otherwise
      benefit from lifestyle and risk factor modification. Recent efforts to improve
      our ability to recognize individuals and populations at increased risk of
      coronary events have focused on the noninvasive imaging of atherosclerosis, both
      in coronary and extracoronary arterial beds, or the identification of "non
      traditional" serum markers. We review the complimentary role of these newer
      methods of risk stratification in the context of conventional risk factor
      evaluation.

PMID- 11594410
TI  - A critique of the new ST-segment criteria for the diagnosis of acute myocardial
      infarction in patients with left bundle-branch block.
AB  - BACKGROUND: Recently, electrocardiogram (ECG) criteria have been proposed for the
      diagnosis of acute myocardial infarction (AMI) in the presence of left bundle
      branch block (LBBB). However, clinical experience indicates that such ECG changes
      indicative of AMI are occasionally noted in clinically stable patients with LBBB,
      raising concerns about the specificity of the proposed criteria. HYPOTHESIS: The
      aim of this study was to evaluate the frequency of ST-segment abnormalities
      suggestive of AMI in ambulatory patients with cardiovascular disease and chronic
      LBBB, who did not have an AMI. In addition, the ECG determinants of such ST
      segment abnormalities were sought. METHODS: The files of all (4,193) patients
      followed in the outpatient cardiology clinic were reviewed to identify patients
      with LBBB. Electrocardiograms of these patients were evaluated as to the duration
      of the QRS complex, frontal QRS axis, amplitude of QRS in leads V1-V3, and the
      presence and magnitude of ST-segment depression (-ST) in leads V1-V3, and ST
      segment elevation (+ST) in leads with predominantly positive or negative QRS
      complexes. Correlations of these ECG variables were carried out. RESULTS: In 124
      patients with LBBB only 1 patient with -ST of 1 mm in leads V1-V3, and 1 patient
      with +ST of 1 mm in a predominantly positive ECG lead were found; the latter
      patient also had +ST of 6 mm in V3. Nine patients were detected with > or = 5 mm
      +ST in at least one ECG lead with predominantly negative QRS complex. Regression
      analysis of amplitude of +STs on corresponding QRS amplitudes in leads V1-V3
      yielded Rs of 0.69, 0.68, and 0.69, all with a p value of 0.00005. A similar
      analysis of the amplitudes of +STs > or = 5 mm with the corresponding QRSs
      yielded an R = 0.76 and a p value of 0.0018. CONCLUSIONS: Thus, recently proposed
      ST-segment criteria for the diagnosis of AMI in patients with LBBB are
      appropriate. However, stable > or = 5 mm +STs are occasionally found in leads
      with predominantly negative QRS complexes, particularly of large amplitude (mean
      value 46.0, range [28.0-71.0] mm) in the absence of AMI. In such patients
      presenting with symptoms suggestive of AMI, further non-ECG confirmation of
      probable underlying AMI should be sought.

PMID- 11594411
TI  - The effect of thrombolytic therapy on left ventricular aneurysm formation in
      acute myocardial infarction: relationship to successful reperfusion and vessel
      patency.
AB  - BACKGROUND: Although there is increasing evidence for the beneficial effect of
      thrombolytic therapy on global left ventricular (LV) function in acute myocardial
      infarction (AMI), the data concerning the early effect of thrombolytic therapy on
      the incidence of left ventricular aneurysm (LVA) formation and its relationship
      to clinical and angiographic determinants are limited. HYPOTHESIS: The study
      aimed to determine the independent factors involved in the development of LVA and
      to evaluate whether thrombolytic therapy has any preventive effect on the
      development of LVA in AMI. METHODS: In all, 350 consecutive patients suffering
      from a first attack of AMI were included. Of these, 205 who arrived within 12 h
      of onset of symptoms received thrombolytic therapy (thrombolytic group) and the
      remaining 145 patients served as control group. All patients received aspirin and
      maximal-dose anticoagulation with intravenous heparin therapy. Early successful
      reperfusion was assessed by enzymatic and electrocardiographic evidence, and late
      vessel patency was evaluated according to Thrombolysis in Myocardial Infarction
      (TIMI) classification. Patients with TIMI grade 2 or 3 flow were considered to
      have vessel patency. RESULTS: The overall incidence of LVA was 11.7% (41/350),
      and no statistical difference was found between the incidence of LVA between the
      two groups (11.7 vs. 11.7%, p>0.05). However, the patients receiving thrombolytic
      therapy and exhibiting a patent infarct-related artery (PIRA) (n = 125, 61%), had
      a significantly reduced incidence of LVA compared with those who did not (7.2 vs.
      18.8%, p= 0.015). In univariate analysis, vessel patency, proximal left anterior
      descending artery (LAD) stenosis, total LAD occlusion, multivessel disease, and
      hypertension were found to be important factors in LVA formation after AMI. After
      adjustment for other clinical and angiographic variables, total LAD occlusion
      (odds ratio [OR] 3.62,95% confidence interval [CI] 2.45-8.42, p = 0.0014),
      absence of PIRA (OR 2.92, 95% CI 1.41-09, p = 0.0037) and proximal LAD stenosis
      (OR 2.11, 95% CI 1.05-4.71, p = 0.045) remained the independent determinants of
      LVA formation after AMI. CONCLUSION: Our data indicate that not all patients who
      received thrombolytic therapy, but only those with PIRA had evidently reduced the
      incidence of LVA. Patients with total LAD occlusion, with proximal LAD stenosis,
      and without PIRA were found to have increased risk for formation of LVA after
      AMI. These findings indicate that the presence of vessel patency has a preventive
      effect on LVA formation in AMI.

PMID- 11594412
TI  - Left ventricular systolic and diastolic function after anthracycline chemotherapy
      in childhood.
AB  - BACKGROUND: In childhood, late cardiotoxicity is characterized by inappropriately
      thin wall and consequent increased end-systolic wall stress, but the associations
      of impaired left ventricular geometry and function occurring under these
      circumstances need further investigation. HYPOTHESIS: The purpose of this study
      was to assess anthracycline late effects on the relationships occurring between
      increased end-systolic stress (ESS) and changes in both M-mode systolic
      measurements (i.e., endocardial and midwall fractional shortening) and Doppler
      diastolic indices in the pediatric age. METHODS: The population consisted of 101
      children treated with anthracyclines for at least 12 months and 91 healthy
      children. Using M-mode echocardiography, end-systolic wall stress was calculated
      as index of afterload, and endocardial and midwall fractional shortening as
      systolic indices. Doppler transmitral measurements were made as diastolic
      indices. RESULTS: Patients treated with anthracyclines showed significantly lower
      relative wall thickness and left ventricular mass index, greater end-systolic
      wall stress, reduced endocardial and midwall fractional shortening and peak E/A
      ratio, prolonged deceleration, and isovolumic relaxation times. Direct
      relationships were found between end-systolic wall stress and both endocardial
      and midwall shortening. The use of midwall shortening in the relation showed a
      greater, but not significant increase (from 3 to 6%) in the proportion of
      patients with depressed systolic function than did endocardial shortening. In the
      anthracycline group, end-systolic wall stress was also inversely related to
      relative wall thickness and directly to isovolumic relaxation time. CONCLUSIONS:
      In childhood, reduced myocardial thickness and increased afterload explain much
      of systolic and diastolic dysfunction of late anthracycline toxicity. Midwall
      fractional shortening does not seem to add useful information for identifying
      subsets of children more prone to the development of heart failure.

PMID- 11594413
TI  - Power motion imaging can improve image quality in stress conditions with
      tachycardia.
AB  - BACKGROUND: Stress echocardiographic studies are useful, but the evaluation of
      wall motion is sometimes suboptimal. The recently developed technique of power
      motion imaging can enhance mobile tissue definition. HYPOTHESIS: The study was
      undertaken to determine whether power motion imaging improves endocardial
      definition during tachycardia compared with conventional two-dimensional (2-D)
      imaging. METHODS: Twenty pigs were studied during pacing rates of 100, 120, and
      150 beats/min. We compared power motion imaging with standard 2-D imaging using
      systolic thickening visualization (STV) scores (3 = excellent definition of
      systolic thickening approximately 0 = total lack of visualization of systolic
      thickening) at each heart rate. We calculated the sum of the scores of 22 left
      ventricular segments as the overall STV score, and also calculated the sum of the
      scores in 10 parasternal segments and 12 apical segments separately. RESULTS: The
      overall STV scores in both imaging methods were similar at 100 beats/min, but
      scores for power motion imaging were significantly higher than those of usual 2-D
      imaging at 120 and 150 beats/min. Using power motion imaging, the overall STV
      scores were similar as heart rate was increased; however, while using standard 2
      D imaging, STV scores were significantly decreased as heart rate was increased.
      Findings were analyzed separately by parasternal and apical images. Especially in
      the parasternal images, the scores were significantly increased as heart rate was
      increased using power motion imaging. CONCLUSIONS: We conclude that power motion
      imaging improves the detection of endocardial border in stress condition with
      tachycardia, and thus this modality is useful for stress echocardiography.

PMID- 11594415
TI  - Cardiac metastasis from testicular mixed germ cell tumor.

PMID- 11594414
TI  - Magnetocardiographic mapping of QRS fragmentation in patients with a history of
      malignant tachyarrhythmias.
AB  - BACKGROUND: The identification of patients at increased risk for ventricular
      tachycardia or ventricular fibrillation (VT/VF) and sudden cardiac death has
      consequences for therapeutic options and thus may reduce mortality in patients
      with coronary artery disease (CAD). HYPOTHESIS: We hypothesized that the intra
      QRS fragmentation in magnetocardiographic recordings is increased in patients
      with CAD and with a history of VT/VF. METHODS: Multichannel magnetocardiography
      (MCG) was carried out in 34 healthy controls, 42 patients with CAD without a
      history of VT/VF, and 43 patients with CAD and with a history of VT/VF. The intra
      QRS fragmentation was quantified by a new fragmentation score. Its spatial
      distribution was investigated using two-dimensional (2-D) contour maps according
      to the sensor position of the 49-channel magnetogradiometer. RESULTS: Patients
      with CAD and with a history of VT/VF had significantly increased QRS
      fragmentation compared with patients with CAD without VT/VF or controls (72.9+/
      37.5, 48.5+/-14.3, and 42.5+/-7.8, respectively: p <0.05). The area of high
      fragmentation in 2-D contour maps was twice as large in patients with than in
      those without a history of VT/VF (represented by the number of MCG channels with
      high fragmentation: 26.3+/-15.5 vs. 12.4+/-9.9, p<0.0001). Patients prone to
      VT/VF could be identified with a sensitivity of 64% and a specificity of 90%.
      CONCLUSION: In patients with CAD and with a history of VT/VF, intra-QRS
      fragmentation is increased and the area of high fragmentation in 2-D contour maps
      is enlarged. These findings may be helpful in identifying patients with CAD at
      risk for malignant tachyarrhythmias.

PMID- 11594416
TI  - Coronary heart disease associated with the use of human immunodeficiency virus
      (HIV)-1 protease inhibitors: report of four cases and review.
AB  - Four cases of human immunodeficiency virus (HIV)-infected patients who developed
      coronary heart disease (CHD) while under treatment with a protease inhibitor (PI)
      are described, and the epidemiologic and clinical features of 18 cases reported
      in the literature are analyzed. Cardiac manifestations mostly included myocardial
      infarctions. Smoking and hyperlipidemia were the most common risk factors for
      CHD, reported in 72 and 81% of the patients, respectively. Hypercholesterolemia
      was observed in 75% of the cases at the time of the cardiovascular event. Ninety
      percent of the patients with pretreatment normal lipid values experienced a rise
      in the plasma lipid levels during PI therapy. Although a definite relationship
      between the development of CHD and HIV PIs can not be made, this analysis
      suggests that PI-induced hyperlipidemia may play a role in accelerating coronary
      atherosclerosis in patients with concomitant risk factors. Evaluation and control
      of risk factors for CHD should be performed in each patient for whom treatment
      with a PI is indicated.

PMID- 11594417
TI  - Desmond Gareth Julian: pioneer in coronary care.

PMID- 11594418
TI  - Ultrasound in acute stroke: a review.
AB  - Ultrasound is widely used for assessment of neurovascular disease, mainly during
      the subacute or chronic phases of cerebral ischaemia. The availability of
      aggressive and potentially harmful treatments for acute ischaemic stroke demands
      fast, and noninvasive examination of the intracranial vasculature. Current
      ultrasound techniques have the potential to provide essential information about
      the intracranial arteries in acute stroke. Application of echo-enhancing agents
      promises to effectively extend current techniques. The clinical significance of
      sonography in acute stroke needs to be evaluated prospectively and compared with
      other radiological techniques.

PMID- 11594419
TI  - Correlating multiple MRI parameters with clinical features: an attempt to define
      a new strategy in multiple sclerosis.
AB  - MRI is the most powerful imaging technique in managing patients with suspected or
      confirmed multiple sclerosis (MS). However, conventional MRI variables show
      nonspecific abnormalities weakly correlated with clinical progression of the
      disease. New techniques, now routinely available, offer better characterisation
      of the pathophysiology. We combined conventional MRI, including lesion load,
      contrast enhancement and "black holes" with magnetisation transfer and diffusion
      weighted imaging and localised proton MR spectroscopy (MRS) to study their
      relationship with disability, course and duration of MS. The variables that were
      the most significantly linked to the course of the disease (relapsing remitting
      versus secondary progressive) were lesion load, mean overall magnetisation
      transfer ratio and apparent diffusion coefficient (MGADC), the percentage of ADC
      in (PADCIMD), and out of (PAD-COMD) modal distribution, and the ratio N
      acetylaspartate and creatine-containing compounds on MRS of the centrum
      semiovale. MGADC and PADCIMD were the independent factors most related to
      disability and duration of disease. Combining MRI techniques is clinically
      relevant and feasible for studies of MS and may be applied to other diseases of
      the central nervous system.

PMID- 11594420
TI  - Lateralisation with magnetic resonance spectroscopic imaging in temporal lobe
      epilepsy: an evaluation of visual and region-of-interest analysis of metabolite
      concentration images.
AB  - We carried out spectroscopic imaging (MRSI) on nine consecutive patients with
      temporal lobe epilepsy being assessed for epilepsy surgery, and nine
      neurologically healthy, age-matched volunteers. A volume of interest (VOI) was
      angled along the temporal horns on axial and sagittal images, and symmetrically
      over the temporal lobes on coronal images. Images showing the concentrations of N
      acetylaspartate (NAA) and of choline-containing compounds plus creatine and
      phosphocreatine (Cho + Cr) were used for lateralisation. We compared assessment
      by visual inspection and by signal analysis from regions of interest (ROI) in
      different positions, where side-to-side differences in NAA/(Cho + Cr) ratio were
      used for lateralisation. The NAA/ (Cho + Cr) ratio from the different ROI was
      also compared with that in the brain stem to assess if the latter could be used
      as an internal reference, e. g., for identification of bilateral changes. The
      metabolite concentration images were found useful for lateralisation of temporal
      lobe abnormalities related to epilepsy. Visual analysis can, with high accuracy,
      be used routinely. ROI analysis is useful for quantifying changes, giving more
      quantitative information about spatial distribution and the degree of signal
      loss. There was a large variation in NAA/ (Cho + Cr) values in both patients and
      volunteers. The brain stem may be used as a reference for identification of
      bilateral changes.

PMID- 11594421
TI  - Comparing the performance of mono- and biplane fluoroscopy systems in diagnostic
      and interventional neuroangiography using the dose-area product.
AB  - Biplane digital imaging systems are favoured in neurointerventional practice
      since they are believed to contribute to safer, quicker and more efficacious
      procedures. Our aim was to establish if such equipment exposes patients to the
      same level of ionising radiation as monoplane systems. We reviewed monoplane and
      biplane fluoroscopy screening times and dose-area products (DAP) for 267
      diagnostic cerebral angiograms and 56 neurointerventional cases. Significantly
      lower DAP for the latter were recorded on the biplane equipment, demonstrating an
      important reduction in patient exposure to radiation. There were no significant
      differences between the two systems for diagnostic cerebral angiography.

PMID- 11594422
TI  - CT during selective arteriography: anatomical assessment of unruptured
      intracranial aneurysms before endovascular treatment.
AB  - Our aim was to investigate the usefulness of helical CT during selective
      angiography (CT arteriography) in pretreatment assessment of unruptured
      intracranial aneurysms. We studied 47 unruptured aneurysms in 34 prospectively
      recruited patients for whom endovascular embolisation was initially considered.
      As pretreatment assessment, we performed rotational digital subtraction
      angiography (DSA) followed by CT arteriography. The findings on axial source
      images (axial images) and reconstructed three-dimensional CT angiography (3D-CTA)
      of CT arteriography were compared to those of rotational DSA, with particular
      attention to the neck of the aneurysm and arterial branches adjacent to it.
      Information provided by CT arteriography was more useful than that of rotational
      DSA as regards the neck in 25 (53%) of 47 cases and as regards branches in 18
      (49%) of 37 aneurysms. On axial images, small arteries such as the anterior
      choroidal artery were seen in some cases. CT arteriography can provide valuable
      additional information about unruptured aneurysms, which cannot be obtained by
      rotational DSA alone. This technique is useful for obtaining anatomical
      information about aneurysm anatomy and for deciding the therapeutic strategy.

PMID- 11594423
TI  - MRI in isolated sixth nerve palsies.
AB  - In previous studies the origin of the majority of isolated sixth nerve palsies
      was not clear or was ascribed to vascular disease. Our purpose was determine how
      frequently a causative lesion was demonstrated on MRI in patients with an acute
      unilateral sixth nerve palsy. We performed a prospective study of 43 patients
      using a standardised protocol. In 27 patients (63%) a lesion was identified on
      the initial MRI relevant to the sixth nerve palsy; 21 (49%) were found to have a
      tumour or tumour-like lesion; the frequency of presumed vasculopathy in this
      group was 15%. There were 16 patients (37%) with an initially normal MRI, of whom
      10 (62%) had a history of vasculopathy, a significantly different proportion from
      the group of patients with a visible causative lesion. MRI after 3-6 months was
      normal in all patients with a normal initial MRI. We suggest that MRI should
      routinely be performed in patients presenting with an acute sixth nerve palsy,
      even those with evidence of a vasculopathy. If the symptoms regress spontaneously
      and there is a history of vasculopathy, follow-up MRI is not necessary.

PMID- 11594424
TI  - MRI evidence of cerebellar and hippocampal involvement in Creutzfeldt-Jakob
      disease.
AB  - We report a 51-year-old woman with the Brownell-Oppenheimer (cerebellar) variant
      of Creutzfeldt-Jakob disease (CJD). She had the typical findings of bilateral
      basal ganglion changes on MRI, as well as changes in the cerebellum and
      hippocampus. This case adds further information to the known imaging
      characteristics of CJD.

PMID- 11594425
TI  - Third ventricular plasma-cell lesion with delayed intraventricular transudation
      of contrast medium.
AB  - We report a patient presenting with hydrocephalus secondary to a posterior third
      ventricular plasma-cell lesion which exhibited delayed transudation of contrast
      medium into the adjacent aqueduct and fourth ventricle.

PMID- 11594426
TI  - Concomitant pituitary adenoma and Rathke's cleft cyst.
AB  - We reviewed the clinical, radiological and surgical findings in patients with
      both pituitary adenoma and Rathke's cleft cyst. We retrospectively selected
      patients with both lesions from the 374 patients in whom a sellar/juxtasellar
      lesion was detected on MRI at 1.5 tesla. All patients received intravenous
      contrast medium. Concomitant pituitary adenoma and Rathke's cleft cyst were found
      in eight patients (2.1 %). The frequency of the combination was 3.5 % of
      pituitary adenomas and 11% of Rathke's cleft cysts. Symptoms were always due to
      the adenoma, secreting adrenocorticotrophin in two patients and growth hormone in
      six. The adenoma was larger in five patients, and the cyst in three. The cysts
      gave variable signal. The adenoma was adjacent to the cyst in seven patients, and
      enclosed it in the other patient. As a result of experience with MRI, concomitant
      pituitary adenoma and Rathke's cleft cyst are now known not to be as rare as
      thought previously. When a non-enhancing cyst-like structure is demonstrated in a
      patient with pituitary adenoma, the possibility of a coexisting Rathke's cleft
      cyst should be considered.

PMID- 11594427
TI  - Suprasellar and infrasellar craniopharyngioma with a persistent craniopharyngeal
      canal: case report and review of the literature.
AB  - Craniopharyngiomas are usually confined to the sellar and suprasellar regions;
      infrasellar craniopharyngioma is rare. From an embryological point of view, this
      unusual localisation can be explained by Erdheim's theory that these tumours can
      arise anywhere along the craniopharyngeal canal (CPC). However, there has been no
      proof of this theory, because the CPC is usually obliterated during the 12th week
      of gestation. I present a case of supra- and infrasellar craniopharyngiomas with
      a persistent CPC. Imaging demonstrated an intimate relationship between the
      infrasellar tumour and the CPC, supporting Erdheim's view.

PMID- 11594428
TI  - Chordoma with postoperative subcutaneous implantation and meningeal
      dissemination: MRI.
AB  - Chordomas are histologically benign tumours which are locally invasive. We
      present an unusual case of recurrent chordoma with subcutaneous implantation and
      widespread meningeal dissemination after surgery. Contrast-enhanced MRI was
      useful for determining the extent of the tumour.

PMID- 11594429
TI  - Persistent hypoglossal artery: MRI, MRA and digital subtraction angiography.
AB  - We present the MRI, MRA and digital subtraction angiography (DSA) findings in a
      persistent hypoglossal artery found incidentally in a patient with cutaneous and
      intracranial haemangiomata.

PMID- 11594430
TI  - Association of distinct intracranial pial and dural arteriovenous shunts.
AB  - Intracranial pial and dural arteriovenous shunts may exist at different sites in
      the same patient. The etiology, natural history and treatment of these associated
      conditions have not been completely determined. We reviewed the records of 765
      cases of pial arteriovenous malformation and 137 dural arteriovenous fistulae and
      malformations. We selected eight patients with both pial and dural arteriovenous
      shunts, separate anatomically, with distinct feeding arteries and draining veins,
      representing 1% of pial and 17% of dural shunts. Presentation was related to the
      dural lesion in 5 cases (62.5 %) and to the pial malformation in three (37.5%).
      Treatment of these lesions should be considered separately based on their angio
      architecture and natural history.

PMID- 11594431
TI  - Comparison of operative and endovascular treatment of anterior circulation
      aneurysms in patients in poor grades.
AB  - We assessed the outcome of surgical and endovascular treatment in patients in
      poor (Hunt & Hess IV or V) grade following subarachnoid haemorrhage due to
      anterior circulation aneurysm (ACA). There were 41 patients, treated surgically
      (20), by the endovascular route (20) or both (1). The aneurysms were clipped in
      20 patients, wrapped in one; 19 were treated with Guglielmi detachable coils
      (GDC), one by parent vessel occlusion using detachable balloons. One GDC
      treatment was interrupted and the aneurysm was surgically clipped instead. We
      treated five patients surgically to evacuate accompanying intracerebral clots. We
      treated 14 (66%) patients by the endovascular route and 15 (71%) surgically
      within 72 h of the haemorrhage. The frequency of delayed ischaemic neurological
      deficit and/or cerebral infarct due to vasospasm did not differ significantly
      between the endovascular and surgical groups. We had one surgical and three
      endovascular procedure-related complications with clinical manifestations.
      Outcome was evaluated after 6 months. After GDC treatment, angiographic follow-up
      was carried out between 8 and 26 months (mean 17 months). Good outcomes were
      achieved in six (29%) of the surgically treated patients (40% of the survivors)
      and six (30%) of the endovascular treatment patients (60% of the survivors).
      Outcome was similar after surgical and endovascular approaches. The decision as
      to which treatment to chosen is influenced mainly by clinical factors such as
      cerebral haematoma or age.

PMID- 11594432
TI  - Endovascular stent-graft treatment of an iatrogenic vertebral arteriovenous
      fistula.
AB  - We present a high-flow vertebral arteriovenous fistula caused by percutaneous
      catheterisation of the internal jugular vein. Endovascular transarterial
      treatment with a self-expanding covered stent was used to close the fistula
      successfully with preservation of the parent artery.

PMID- 11594433
TI  - The dorsal cyst in holoprosencephaly and the role of the thalamus in its
      formation.
AB  - The dorsal cyst is poorly understood, although it is commonly encountered in
      holoprosencephaly. We endeavor to establish the role of diencephalic
      malformations in the formation of the dorsal cyst and speculate on the
      developmental factors responsible. We reviewed the imaging of 70 patients with
      holoprosencephaly (MRI of 50 and high-quality CT of 20). The presence or absence
      of a dorsal cyst, thalamic noncleavage and abnormal thalamic orientation were
      assessed for statistical association, using Fisher's Exact Test and logistical
      regression. The presence of a dorsal cyst correlated strongly with the presence
      of noncleavage of the thalamus (P = 0.0007) and with its degree (P < 0.00005).
      There was a trend toward an association between abnormalities in the orientation
      of the thalamus and the dorsal cyst, but this was not statistically significant
      (P = 0.07). We speculate that the unseparated thalamus physically blocks egress
      of cerebrospinal fluid from the third ventricle, resulting in expansion of the
      posterodorsal portion of the ventricle to form the cyst.

PMID- 11594434
TI  - MRI in nonketotic hyperglycinaemia: case report.
AB  - We present a girl with proven nonketotic hyperglycinaemia. The pathological
      findings on MRI were brain atrophy with thinning of the corpus callosum and
      delayed myelination of the cerebral hemispheres, particularly the parietal lobes.

PMID- 11594435
TI  - Pentobarbital-induced place preference in rats is blocked by GABA, dopamine, and
      opioid antagonists.
AB  - RATIONALE: Drugs that are self-administered usually produce a conditioned place
      preference (CPP) but pentobarbital is self-administered by both animals and
      humans and is reported to be aversive in the CPP test. OBJECTIVES: We tested
      whether pentobarbital (5, 15, and 25 mg/kg; IP) could produce a place preference
      and examined the role of GABA, dopamine (DA) and opioid receptors in the
      pentobarbital CPP. METHODS: Place conditioning was carried out in an apparatus
      consisting of two compartments connected by an alley at the rear. During the pre
      exposure and test phase, the rats were free to wander in the apparatus for 20
      min, and were drug-free. During the 6-day conditioning phase, rats were injected
      with drug (or vehicle), and confined to one compartment for 30 min and on
      alternate days were injected with vehicle (or drug) and confined to the other
      compartment. Upon obtaining a CPP, we examined whether pretreatment of the GABAA
      antagonists picrotoxin or bicuculline (0.5, 1.0, and 2.0 mg/kg; IP), the DA
      antagonist eticlopride (0.01, 0.05, and 0.25 mg/kg; SC), or the opioid antagonist
      naloxone (0.02, 0.20, and 2.0 mg/kg; IP) would block the CPP. RESULTS: 15 mg/kg
      pentobarbital produced a CPP. The pentobarbital CPP was blocked by pretreatment
      of 1.0 and 2.0 mg/kg bicuculline, but not by 0.5, 1.0, or 2.0 mg/kg picrotoxin.
      The pentobarbital CPP was also blocked by 0.05 and 0.25 mg/kg eticlopride and by
      all of the doses of naloxone tested. CONCLUSIONS: Pretreatment with the
      antagonists bicuculline, eticlopride, and naloxone blocked a 15 mg/kg
      pentobarbital CPP. This indicates that GABAergic, dopaminergic, and opioid
      systems play a role in the reinforcing properties of pentobarbital.

PMID- 11594436
TI  - Alprazolam withdrawal and tolerance measured in the social conflict test in mice.
AB  - RATIONALE: It is difficult to assess withdrawal from benzodiazepines, and
      preclinical assessment of behaviour during social conflict offers the opportunity
      to quantify tolerance and withdrawal by measuring aggressive, defensive and
      social behaviour. The relationship between benzodiazepine withdrawal symptoms and
      the development of tolerance is not well understood. Are withdrawal symptoms
      dependent on the development of tolerance? OBJECTIVE: The aim of the present
      study was to compare the development of tolerance to alprazolam effects on the
      behavioural repertoire during the social conflict test in mice, and to determine
      whether or not behavioural changes during alprazolam withdrawal are correlated
      with the development of tolerance. METHODS: An experimental model consisting of
      interactions of pairs of singly housed male mice with non-aggressive group-housed
      male mice was used. Alprazolam (1 mg/kg) was given orally once or repeatedly
      (twice daily) for 8 or 21 days. Behaviour was measured, based on videoanalysis,
      in aggressive mice before treatment, 30 min or 3 days after the last dose,
      respectively. RESULTS: A single administration of alprazolam significantly
      reduced aggressive activities and increased social investigation without changing
      locomotion or other behaviour. Tolerance developed to the inhibitory effects of
      alprazolam on aggressive behaviour but not to the effects of alprazolam to
      increase social investigation. When withdrawn from alprazolam, mice exhibited
      less social investigation and locomotion while aggression tended to be increased.
      CONCLUSIONS: Tolerance to the alprazolam effects on aggressive and social
      behaviour developed at different rates suggesting that they are differentially
      regulated. Furthermore, the evidence of withdrawal responses appearing in a
      behaviour to which tolerance had not developed does suggest that tolerance and
      withdrawal phenomena are dissociated in benzodiazepines.

PMID- 11594437
TI  - Zolmitriptan--a 5-HT1B/D agonist, alcohol, and aggression in mice.
AB  - RATIONALE: Zolmitriptan is an anti-migraine agent with action at 5-HT1B/D
      receptors. It penetrates into the central nervous system and, like other 5-HT1B/D
      agonists, its pharmacotherapeutic profile may include significant anti-aggressive
      effects. OBJECTIVES: To examine whether zolmitriptan has potential anti
      aggressive effects by studying two kinds of aggressive behavior in mice--species
      typical and aggression under the influence of alcohol. A second objective was to
      study whether pre- or post-synaptic receptors mediate these anti-aggressive
      effects. METHODS: Initially, the anti-aggressive effects of zolmitriptan were
      studied in male CFW mice during 5-min resident-intruder confrontations. To
      confirm the 5-HT1B receptor as a critical site of action for the anti-aggressive
      effects, the zolmitriptan dose-effect determinations were repeated after
      pretreatment with GR 127935 (10 mg/kg, i.p.). In further experiments, mice were
      treated concurrently with alcohol (1.0 g/kg, p.o.) and zolmitriptan (1-30 mg/kg,
      i.p.) in order to compare the effects of this agonist on species-typical and
      alcohol-heightened aggression. Finally, mice were infused with the neurotoxin 5,7
      DHT (10 microg) into the raphe area to eliminate somatodendritic and presynaptic
      autoreceptors. The anti-aggressive effects of zolmitriptan (17 mg/kg, i.p.) or CP
      94,253 (10 mg/kg, i.p.) were assessed 10 days after the lesion, and levels of 5
      HT and 5-HIAA were measured in the hippocampus and prefrontal cortex. RESULTS:
      Zolmitriptan exerted behaviorally specific anti-aggressive effects. The reduction
      in aggression was antagonized by GR 127935, indicated by a rightward shift in the
      dose-effect curves of zolmitriptan, showing the specificity for the 5-HT1B
      receptors. Zolmitriptan also decreased alcohol-heightened aggression with equal
      efficacy. The anti-aggressive effects of CP-94,253 and zolmitriptan remained
      unaltered by 5,7-DHT lesions that depleted cortical and hippocampal 5-HT by 60
      80%. CONCLUSIONS: Zolmitriptan proved to be an effective and behaviorally
      specific anti-aggressive agent in situations that engender moderate and alcohol
      heightened levels of aggression. These effects are potentially due to activation
      of post-synaptic 5-HT1BD receptors.

PMID- 11594438
TI  - Differential effects of delta 9-THC on spatial reference and working memory in
      mice.
AB  - RATIONALE: Marijuana remains the most widely used illicit drug in the U.S., and
      recent attention has been given to putative therapeutic uses of marijuana and
      cannabinoid derivatives. Thus, developing a better understanding of delta9-THC
      (tetrahydrocannabinol)-induced mnemonic deficits is of critical importance.
      OBJECTIVES: These experiments were conducted to determine whether delta9-THC has
      differential effects on spatial reference and working memory tasks, to
      investigate its receptor mechanism of action, and to compare these effects with
      those produced by two other compounds--scopolamine and phencyclidine--known to
      produce mnemonic deficits. In addition, the potency of delta9-THC in these memory
      tasks was compared with its potency in other pharmacological effects
      traditionally associated with cannabinoid activity. METHODS: Two different
      versions of the Morris water maze were employed: a working memory task and a
      reference memory task. Other effects of delta9-THC were assessed using standard
      tests of hypomotility, antinociception, catalepsy, and hypothermia. RESULTS:
      delta9-THC disrupted performance of the working memory task (3.0 mg/kg) at doses
      lower than those required to disrupt performance of the reference memory task
      (100 mg/kg), or elicit hypomotility, antinociception, catalepsy, and hypothermia.
      These performance deficits were reversed by SR 141716A. The effects of delta9-THC
      resembled those of scopolamine, which also selectively disrupted the working maze
      task. Conversely, phencyclidine disrupted both tasks only at a dose that also
      produced motor deficits. CONCLUSIONS: These data indicate that delta9-THC
      selectively impairs performance of a working memory task through a CB, receptor
      mechanism of action and that these memory disruptions are more sensitive than
      other pharmacological effects of delta9-THC.

PMID- 11594439
TI  - Enadoline, a selective kappa opioid agonist: comparison with butorphanol and
      hydromorphone in humans.
AB  - RATIONALE: The availability of the highly selective and specific kappa opioid
      agonist enadoline provides an opportunity to explore the function of kappa
      receptors in humans and their potential utility as a target for substance abuse
      pharmacotherapy development. OBJECTIVES: The purpose of this study was to
      characterize the pharmacodynamic effects of enadoline, a selective kappa agonist,
      and to compare it with butorphanol, a mixed mu/kappa agonist, and hydromorphone,
      a mu agonist, in humans. METHODS: Pilot evaluation (n=3) served to establish
      intramuscular doses of enadoline (20, 40, 80, and 160 microg/70 kg), butorphanol
      (1.5, 3, 6, and 12 mg/70 kg), and hydromorphone (1.5, 3, and 6 mg/70 kg) of
      comparable activity. These acute doses were examined under double-blind, placebo
      controlled and constrained randomized conditions with a minimum of 72 h between
      tests in volunteers with polysubstance abuse histories (n=6). Physiological and
      subject- and observer-rated measures were collected 30 min before and for 4 h
      after administration. RESULTS: Enadoline significantly increased measures of
      sedation, confusion and dizziness, produced visual distortions and feelings of
      depersonalization, and increased urinary output. The highest dose (160 microg/70
      kg) was not tolerated and led to psychotomimetic effects. Hydromorphone produced
      prototypic mu opioid effects including respiratory depression, miosis, and
      euphoria. Butorphanol was most similar to hydromorphone and shared few effects
      with enadoline. CONCLUSIONS: These results are discussed with respect to the
      potential use and safety of kappa agonists for clinical indications.

PMID- 11594440
TI  - Effects of short-term citicoline treatment on acute cocaine intoxication and
      cardiovascular effects.
AB  - RATIONALE: The majority of pharmacotherapies proposed for cocaine dependence have
      been marginally effective and frequently have undesirable side effects. We
      recently demonstrated that short-term treatment with citicoline decreased self
      reported desire to use cocaine in crack cocaine users. OBJECTIVE: The present
      study was conducted to assess the safety of citicoline in combination with
      cocaine by investigating whether cocaine-induced cardiovascular and behavioral
      effects and cocaine plasma levels are altered by citicoline pretreatment.
      METHODS: Eight healthy male and female volunteers who used cocaine on an
      occasional basis participated in this randomized, placebo-controlled, three-visit
      study. During all three visits, subjects received an acute intranasal dose of
      cocaine (0.9 mg/kg) and were continuously monitored for the ensuing 3.5 h. The
      first visit involved no pretreatment, and visits 2 and 3 were preceded by a 4-day
      pretreatment period of either citicoline (1 g/day) or placebo. RESULTS:
      Citicoline pretreatment did not alter the cardiovascular, physiologic, or
      subjective effects of acute cocaine. CONCLUSIONS: Although citicoline did not
      block the acute subjective effects of cocaine in a laboratory environment, the
      combined use of citicoline and a moderate dose of intranasal cocaine presented no
      added risk of cardiovascular effects. Further study is necessary to determine
      whether this medication (which is currently used to treat strokes) will be a
      useful adjunct to treat cocaine dependence.

PMID- 11594441
TI  - Drug-induced receptor occupancy: substantial differences in measurements made in
      vivo vs ex vivo.
AB  - RATIONALE: The number of receptors occupied by a given drug is a central
      construct in understanding drug action in the brain. Two techniques have been
      commonly used to measure drug receptor occupancy. In one method, the drug and the
      radioligand used to measure occupancy compete in vivo while in the other method,
      the drug is injected into the living animal, the animal killed and the
      radioligand competes for available receptors ex vivo. While these methods are
      often used interchangeably, there has been no systematic comparison of their
      sensitivities and consistency. OBJECTIVES: In this study, we performed a
      systematic within-animal comparison of drug-induced receptor occupancy as
      measured by the in vivo vs the ex vivo methods. METHODS: We examined the
      occupancy of dopamine Do receptors by different doses of the drug raclopride
      using the in vivo and ex vivo autoradiographic methods in the same rat with 11C
      raclopride and 3H-raclopride as radioligands, respectively. RESULTS: The in vivo
      method showed a significantly greater sensitivity and internal consistency while
      the ex vivo method was less sensitive, and increasingly so as a function of
      longer incubation times. The lack of sensitivity was accounted for by the
      unidirectional dissociation of the drug from the receptors in the incubation
      medium. CONCLUSIONS: Our data suggest that these two methods are not
      interchangeable; the ex vivo method is much less sensitive, lacks internal
      consistency and hence is best avoided.

PMID- 11594442
TI  - No evidence for latent learning of liking for flavours conditioned by caffeine.
AB  - RATIONALE: The ability of caffeine to condition liking for flavours depends on
      the caffeine deprivation status of subjects; however, it is not known if a latent
      liking for a flavour can be acquired in an undeprived state, which subsequently
      emerges when consumers are caffeine deprived. OBJECTIVES: To determine if
      exposure of undeprived caffeine consumers to a novel drink containing caffeine
      leads to increased liking for this drink when they are subsequently tested when
      caffeine-deprived. METHODS: In a double-blind placebo controlled study, four
      groups of 13 moderate caffeine consumers evaluated a novel flavoured drink on 5
      days. The test group consumed this drink with 100 mg caffeine when undeprived on
      days 1-4, and in a deprived state on day 5. Three control groups had the same
      conditions on all 5 days, with an undeprived group receiving the caffeinated
      drink, and two deprived groups receiving the drink with caffeine or placebo.
      RESULTS: The pleasantness of the drink did not change over the 4 training days in
      the test group, and did not alter when this group was tested when caffeine
      deprived. At no stage did these ratings differ between the test and undeprived
      control groups. Pleasantness increased significantly over the 5 days in the
      deprived group who received caffeine, and decreased in the deprived group who
      received placebo. CONCLUSIONS: These results suggest that repeated pairing of a
      novel flavour with the effects of caffeine in subjects who are not caffeine
      deprived does not lead to an emergent liking for that flavour when subsequently
      tested caffeine-deprived. However, the pleasantness of the same caffeinated drink
      increased if it was consumed when caffeine deprived.

PMID- 11594443
TI  - Sertindole is a serotonin 5-HT2c inverse agonist and decreases agonist but not
      antagonist binding to 5-HT2c receptors after chronic treatment.
AB  - RATIONALE: Sertindole is a novel antipsychotic drug with high affinity for
      dopamine D2, alpha-1-adrenoceptors and serotonin 5-HT2A and 5-HT2c receptors. The
      5-HT2c receptor component of sertindole may be clinically relevant as this
      receptor subtype is implicated in regulation of anxiety, cognition/memory and
      brain plasticity. OBJECTIVE: To characterise the interaction of sertindole with
      the 5-HT2C receptor using rat choroid plexus as a physiological receptor source.
      RESULTS: Sertindole had nanomolar affinity for the 5-HT2c receptor in vitro.
      Sertindole antagonised 5-HT-stimulated phosphoinositide (PI) hydrolysis and, like
      clozapine, also inhibited basal PI hydrolysis suggesting that sertindole is a 5
      HT2C receptor inverse agonist. The effect of repeated sertindole dosing on 5-HT2C
      receptors was studied in rats treated for 21 days with sertindole (20, 300 and
      1250 microg/kg/day). Clozapine (25 mg/kg/day) was used as a comparison drug. 5
      HT2C receptor binding in the choroid plexus was measured with antagonist and
      agonist ligands ([3H]mesulergine and [125I]DOI) using quantitative
      autoradiography 8 days after withdrawal. Clozapine decreased 5-HT2C receptor
      antagonist and agonist binding sites equally by 36% and 32%, respectively.
      Sertindole did not induce significant changes in the total number of 5-HT2C
      receptors, but the highest dose of sertindole lowered the affinity of
      [3H]mesulergine for 5-HT2C receptors. This was most likely due to residual
      sertindole levels in the brain which was supported by direct concentration
      measurements. In contrast, sertindole induced a highly significant and dose
      related decrease in 5-HT2C agonist binding (up to 77%). Neither drug affected
      striatal D2 receptor binding. CONCLUSIONS: Sertindole, like clozapine, was found
      to be a serotonin 5-HT2C receptor inverse agonist. The preferential
      downregulation of 5-HT2C receptor agonist (G-protein-coupled) sites by chronic
      administration seemed to differentiate sertindole from clozapine at these dose
      regimens. The 5-HT2c receptor downregulation during repeated dosing may
      contribute to therapeutic efficacy and/or side effects of sertindole treatment.

PMID- 11594444
TI  - Auditory threshold reduction on alcohol ingestion.
AB  - RATIONALE: Auditory threshold (AT) measurement method has become the standard
      behavioral procedure for describing auditory sensitivity. Therefore, the AT
      measurement method is applicable to evaluation of auditory function. However,
      only a few studies have been performed to clarify the alteration of audibility
      under the influence of alcohol on normal humans by measurement of AT. OBJECTIVE:
      The fact that blood alcohol concentration (BAC) is influenced by the dose of
      alcohol and the time of measurement suggests that the effects of alcohol may also
      be altered by the same factors. The present study was conducted to elucidate how
      alcohol ingestion method affects the AT at a wider range from lower to higher
      frequency in the time course. METHODS: Fifteen paid Japanese (seven men and eight
      women, 20-33 years of age) were employed in AT measurements at an octave
      frequency ranging from 250 to 8,000 Hz before and 5, 30, 60, 120, 240 and 480 min
      after drinking various amounts (125, 250, 500 and 1,500 ml) of normal beer (5%
      alcohol) or alcohol-free beer. RESULTS: The AT was significantly reduced within
      30 min after the ingestion of 250 and 500 ml of beer, occurring on and after peak
      BAC. The reducing effect disappeared 480 min after ingestion. CONCLUSIONS:
      Drinking extra small amounts of alcohol induces the reduction of AT. The effect
      of alcohol on AT is altered by the alcoholic dose used in testing.

PMID- 11594445
TI  - Acute anorectic effect of single and combined drugs in mice using a non
      deprivation protocol.
AB  - RATIONALE: Studies of the effect of anorectic drugs such as fenfluramine in mice
      have indicated the desirability of using experimental protocols that do not
      involve deprivation. OBJECTIVE: We have developed a non-deprivation or "dessert"
      protocol for use in mice that are maintained in standard housing conditions, and
      examine the effects of a serotonergic agent dexfenfluramine (DFEN), a
      dopaminergic agent phentermine (PHEN), and a selective norepinephrine uptake
      inhibitor thionisoxetine (TNIX) alone and in combination. METHODS: Female
      C57BL/6J mice were adapted to 30 min daily presentation of a gelatinized form of
      sweetened milk using a holder that hooks over the side of the cage during tests;
      food spillage and contamination are minimal. Dose-inhibition curves were
      determined for DFEN, PHEN, and TNIX alone and for fixed ratio combinations of
      DFEN with either PHEN or TNIX. RESULTS: Each drug produced a near linear dose
      inhibition curve with the 50% inhibitory doses (DI50) of 5.6, 3.2 and 12.2 mg/kg,
      respectively. By isobolographic analysis, the effects of the drug combinations
      were strictly additive. CONCLUSION: The procedure described is highly suitable
      for testing anorectic drugs in mice and is adaptable to a variety of housing
      conditions and diets. The DFEN+ PHEN combination was additive, which contrasts
      with its reported supra-additive effect in rats.

PMID- 11594446
TI  - Influence of caffeine, cold and exercise on multiple choice reaction time.
AB  - RATIONALE: The effects of caffeine on psychomotor performance have been evaluated
      under resting conditions and in a thermoneutral environment. Our hypothesis was
      that these effects could be modified by factors enhancing the level of alertness,
      such as exercise and cold exposure. OBJECTIVE: The purpose of this study was to
      follow up changes in the multiple choice reaction time (RT) during exercise at
      room and low ambient temperatures after caffeine or placebo administered in a
      double blind manner. METHODS: Nine soccer players performed multistage,
      incremental exercise until volitional exhaustion on a bicycle ergometer at 22
      degrees C or 4 degrees C, 1 h after ingestion of coffee with caffeine (CAF) or
      without it (PL). Immediately before exercise and at the end of each workload, RT
      and blood lactate (LA) were measured. Oxygen uptake (VO2) and heart rate (HR)
      were recorded continuously. Blood LA threshold and the workload associated with
      the shortest RT were determined. RESULTS: During exercise at 22 degrees C, RT was
      significantly shorter in CAF than in the PL test, while at 4 degrees C there were
      no differences in RT between CAF and PL trials. Cold exposure did not affect RT
      either at rest or during exercise. Neither caffeine nor cold exposure influenced
      the maximal VO2, the maximal HR and LA threshold. CONCLUSION: In the
      thermoneutral environment, caffeine ingestion improved psychomotor performance
      during exercise, whilst at low ambient temperature this effect was blunted. These
      findings suggest that the stimulating action of caffeine depends on the level and
      source of arousal.

PMID- 11594447
TI  - The effects of reboxetine on autonomic and cognitive functions in healthy
      volunteers.
AB  - RATIONALE: Though reboxetine, a selective noradrenaline reuptake inhibitor,
      causes autonomic and cognitive adverse events there is a paucity of appropriately
      designed studies on the cognitive and autonomic effects of the drug in the
      literature. OBJECTIVE: To compare the effects of reboxetine on cognitive and
      autonomic functions with those of placebo in healthy humans. METHOD: A
      randomised, double-blind, crossover study of 12 healthy male volunteers aged 25
      (21-27; median, range) years. Subjects orally received 4 mg reboxetine and
      placebo twice daily for periods of 14 days each with at least 14 days in between.
      Vasoconstrictory response of cutaneous vessels (VR) and skin conductance response
      (SCR) following sudden deep breath were employed as parameters for autonomic
      function. Quantitative EEG (qEEG) and psychometric tests served as parameters for
      cognitive function. RESULTS: Reboxetine decreased SCR and prolonged the dilation
      phase of VR (P<0.05). It did not affect cognitive functions such as flicker
      fusion frequency, choice reaction, memory and psychomotor coordination but
      increased slow beta (beta1) power density in the qEEG. Tiredness (n=12), dry
      mouth (n=9), delayed urination (n=3) and constipation (n=1) were noted with
      reboxetine. CONCLUSION: Sustained peripheral and/or central sympathetic
      activation accounts for the prolongation of VR. The decrease of SCR and typical
      side effects suggest a relevant antimuscarinic drug action. Chronic
      administration of reboxetine at therapeutic doses causes autonomic dysfunction
      and subjective sedation but does not impair cognitive and psychomotor abilities
      in healthy humans.

PMID- 11594448
TI  - Modulation of cocaine and food self-administration by low- and high-efficacy D1
      agonists in squirrel monkeys.
AB  - RATIONALE: Dopamine D1 ligands have been proposed as candidate medications for
      cocaine abuse. Previous studies have shown that the ability of D1 ligands to
      modulate the behavioral effects of cocaine may depend on agonist efficacy.
      OBJECTIVES: This study investigated the role of agonist efficacy in the ability
      of D1 ligands to modulate the reinforcing effects of cocaine in monkeys. METHODS:
      Squirrel monkeys trained to self-administer cocaine under a second-order schedule
      of reinforcement were treated daily with D1 agonists varying in efficacy from low
      to high (SKF 83959 < SKF 77434 < or = SKF 81297 < SKF 82958) and the D1
      antagonist SCH 39166. RESULTS: D1 ligands, regardless of efficacy, produced dose
      dependent reductions in responding maintained by a maximally effective dose of
      cocaine. Equivalent doses of each D1 ligand reduced responding for food under a
      similar second-order schedule, suggesting that the suppression was not specific
      to cocaine self-administration. When studied in combination with a range of
      cocaine doses, treatment with the agonists SKF 83959, SKF 77434, SKF 81297, and
      the antagonist SCH 39166 produced overall rightward and downward shifts in the
      dose-response function for cocaine self-administration. Treatment with the
      agonist SKF 82958, however, produced an overall suppression of responding,
      regardless of the dose of cocaine. CONCLUSIONS: In contrast to a high-efficacy
      agonist, low-efficacy D1 ligands modulated the reinforcing effects of cocaine in
      a manner consistent with at least a partial antagonism of cocaine self
      administration. This delineation of the efficacy-dependent profile of effects for
      D1 ligands should guide research into their utility as cocaine pharmacotherapies.

PMID- 11594449
TI  - Withdrawal from chronic morphine administration causes prolonged enhancement of
      immobility in rat forced swimming test.
AB  - RATIONALE: Opiate-dependent subjects experience severe depression as one of the
      subjective symptoms during withdrawal. No experimental work, however, has focused
      on the ability of opiate-withdrawal to produce depression-like behavior in
      dependent animal. OBJECTIVES. We therefore investigated whether withdrawal from
      chronic morphine treatment affects immobility in forced swimming test in rats.
      METHODS: Morphine was administered in a dose escalation fashion using doses
      ranging from 20 to 140 mg/kg twice daily for 14 days, followed by 1-6 days of
      withdrawal, and their duration of immobility was assessed. RESULTS: After the
      last morphine treatment. an increase in immobility occurred late on day 3 and
      persisted to at least day 6 of withdrawal without any change in ambulatory
      activity. CONCLUSIONS: The results suggest that the morphine withdrawal resulted
      in prolonged enhancement of depression-like behavior in drug-dependent laboratory
      animals.

PMID- 11594450
TI  - Chemokine expression and viral infection of the central nervous system:
      regulation of host defense and neuropathology.
AB  - An effective host response against viral infection of the central nervous system
      (CNS) is the principal factor dictating the outcome of infection. It is the
      responsibility of the immune response to contain and control viral replication.
      Paradoxically, it is the immune response that may also contribute to the
      development of neuropathology. We have used mouse hepatitis virus (MHV),
      apositive-strand RNA virus, infection of the CNS to understand the dynamic
      interaction between viral replication, protection, and pathology with an emphasis
      on understanding how chemokines participate in these interrelated processes.
      Herein, we demonstrate the complexity of the chemokine response to MHV infection
      of the CNS and the delicate balance that exists between host defense and
      development of disease.

PMID- 11594451
TI  - Pathogenesis of virus-induced immune-mediated demyelination.
AB  - Theiler's murine encephalomyelitis virus-induced demyelinating disease has been
      extensively studied as an attractive infectious model for human multiple
      sclerosis. Virus-specific inflammatory Th1 cell responses followed by autoimmune
      responses to myelin antigens play a crucial role in the pathogenic processes
      leading to demyelination. Antibody and cytotoxic T cells (CTL) responses to virus
      appears to be primarily protective from demyelinating disease. Although the role
      of Th1 and CTL responses in the induction of demyelinating disease is
      controversial, assessment of cytokines produced locally in the central nervous
      system (CNS) during the course of disease and the effects of altered inflammatory
      cytokine levels strongly support the importance of Th1 responses in this virus
      induced demyelinating disease. Induction of various chemokines and cytokines in
      different glial and antigen presenting cells upon viral infection appears to be
      an important initiation mechanism for inflammatory Th1 responses in the CNS.
      Coupled with the initial inflammatory responses, viral persistence in the CNS may
      be a critical factor for sustaining inflammatory responses and consequent immune
      mediated demyelinating disease.

PMID- 11594452
TI  - Lupus autoantigens: their origins, forms, and presentation.
AB  - The immune system has developed a number of mechanisms by which to distinguish
      self from foreign proteins. These mechanisms are found throughout the ontogeny of
      B and T cell development and include the deletion of autoreactive cells in
      central lymphoid organs and the induction of self-tolerance in the periphery.
      However, any failure of these mechanisms for self-tolerance may result in
      autoimmune disease. Efforts in our laboratory have been directed at understanding
      how autoimmunity is initiated and maintained in both the B and T cell
      compartment, with particular interest in the autoimmunity of systemic lupus
      erythematosus (SLE). This review will focus on our studies on the forms of self
      antigens that may be involved in the original "antigenic sin" of SLE and in the
      role of B lymphocytes as autoantigen presenting cells. We will also discuss
      whether costimulation is a formal requirement for the induction and maintenance
      of autoimmunity. Finally, we have provided a model for how all of these
      individual elements may contribute to the autoimmune processes leading to
      pathology.

PMID- 11594453
TI  - The transcription factor, Bright, and immunoglobulin heavy chain expression.
AB  - Bright, or B cell regulator of immunoglobulin heavy chain transcription, is a B
      lymphocyte-specific protein first discovered for its ability to increase
      immunoglobulin transcription three- to sevenfold in antigen-activated B cells. It
      interacts with DNA through an ARID, or A/T-rich interaction domain, and is the
      only member of a previously undescribed family of DNA-binding proteins for which
      target genes have been identified. The mechanism(s) by which Bright facilitates
      transcription are unknown. Several proteins that associate with Bright may shed
      light upon its function. These include the nuclear matrix proteins sp100 and
      LYSp100B, and suggest that Bright may affect chromatin configuration and nuclear
      sublocalization. Furthermore, Bruton's tyrosine kinase is required for Bright
      binding activity, suggesting links between Bright, cell signaling cascades, and X
      linked immunodeficiency disease.

PMID- 11594454
TI  - C-reactive protein, inflammation, and innate immunity.
AB  - The circulating acute phase reactant C-reactive protein (CRP) has traditionally
      been characterized as an effector of nonclonal host resistance since it activates
      the classical complement cascade and mediates phagocytosis, but it is also
      capable of regulating inflammation. The three-dimensional structure of human CRP
      has revealed the molecular basis for complement activation and binding of
      phosphate monoesters. CRP gene expression by liver hepatocytes in response to
      cytokines (IL-1beta and IL-6) released in tissues requires several transcription
      factors which interact. Elevated levels of CRP are a prognostic marker for
      coronary artery disease; however, the role of CRP in atheriosclerosis remains
      unknown. CRP also mediates direct host protection to some microbial pathogens via
      its opsonic activity through certain Fcgamma-receptors. The CRP response may be
      one of the links between nonspecific innate immunity and specific clonal
      immunity.

PMID- 11594455
TI  - Lung transplantation and bronchiolitis obliterans: an evolution in understanding.
AB  - Major advancements in the field of lung transplantation have occurred over the
      past thirty-five years. Despite these advancements, limitations in our ability to
      obtain sufficient numbers of organs and in our comprehension of the problems
      associated with the procedure persist. The purpose of this article is to review
      the current understanding of both the surgical procedure and its most unfortunate
      complication, bronchiolitis obliterans. Even now, after over three decades of
      experience, this complication remains the most significant cause of morbidity and
      mortality following lung transplantation. This article is not meant to be an
      exhaustive review, and certainly there are important topics not covered herein.
      We have focused the discussion on ongoing studies, which attempt to understand
      bronchiolitis obliterans at both the clinical as well as the immunopathological
      level.

PMID- 11594456
TI  - Mechanisms of signal transduction activated by sublytic assembly of terminal
      complement complexes on nucleated cells.
AB  - The sublytic assembly of C5b-7, C5b-8, and C5b-9, activates membrane
      phospholipases through heterotrimeric G proteins and stimulates a variety of
      cellular activities including prostanoids, leukotrienes, and cytokines synthesis.
      Activation of mitotic signaling through Ras, Raf-1, ERK1, and
      phosphatidylinositol-3 kinase (PI3-K) was induced in B lymphocytes, endothelial,
      and smooth muscle cells. PI3-K activation by C5b-9 induced STAT3 phosphorylation
      and translocation from cytoplasm to nucleus. This complex signaling mechanism is
      directly involved in many biological functions such as endo- and exocytosis, cell
      cycle progression, activation of transcription, and protein synthesis. The key
      role of this signaling pathway is reflected on cell survival and proliferation in
      acute and chronic inflammation where complement activation is an ubiquitous
      event.

PMID- 11594457
TI  - Regulation of tumor growth by IFN-gamma in cancer immunotherapy.
AB  - Tumor immunity involves a concerted interplay between cytokines and effector
      cells. Extensive efforts have focused on understanding the roles of cytokines and
      their interactions with effector cells for the production of effective tumor
      immunity. One cytokine that is well recognized to play a central role in
      coordinating tumor immune responses is IFN-gamma. IFN-gamma exerts its biological
      effects through interaction with an IFN-gamma receptor that is ubiquitously
      expressed on nearly all cells. In this review, we discuss the positive and
      negative effects of IFN-gamma signaling in the tumor cell on tumor growth.

PMID- 11594458
TI  - Of mice and men: the relevance of the mouse to the study of human SLE.
AB  - A number of mouse models have been utilized to study the pathophysiology of
      immune complex (IC) disease, and the hallmark IC disease systemic lupus
      erythematosus (SLE). Many of these studies have provided exciting new insights
      into IC-mediated inflammation and autoimmunity. However, numerous differences
      exist between mice and humans that suggest that mouse studies are not always
      applicable to human disease. These differences can be found in the biological
      systems that interact with circulating IC, in the specifics of disease
      presentation, and in the general physiology of the two species. Furthermore,
      although the mechanisms of SLE-like autoimmune disease in the mouse are being
      defined through analyses of the murine models of SLE, it remains to be proven
      that these mechanisms are relevant to human SLE. Thus, generalizing the results
      of the mouse studies to human SLE and other human IC diseases must be done with
      caution.

PMID- 11594460
TI  - Purification and partial amino acid sequence of proteins from human epidermal
      keratinocyte conditioned medium.
AB  - Keratinocytes are the main cell type of the epidermis. They secrete a variety of
      proteins and peptides that have diverse roles in epidermal physiology. In this
      report, we present purification and partial amino acid sequence of LEKTI, a
      serine proteinase inhibitor, and DAN (NO3) zinc-finger protein, a tumor
      suppressor protein of neuroblastoma, from human keratinocyte conditioned medium.
      Epidermal keratinocytes were isolated from human foreskin and serially passaged
      in a defined medium (MSBM). At confluence of the fourth passage, MSBM medium was
      replaced with protein-free Dulbecco's modified Eagle medium/F12 (DMEM:F12) 3:1
      base medium and collected every 24 h for 4 days. Medium was pooled and
      concentrated using a stirred cell concentrator. Concentrated medium was diluted
      1:1 in 50 mM sodium phosphate, pH 8 buffer, and loaded onto a preparative heparin
      affinity column. Proteins/peptides were purified from heparin column passthrough
      by the combination of preparative and analytical FPLC-based gel filtration
      chromatography and reversed-phase HPLC. Samples electroblotted onto a PVDF
      support were sequenced by Edman degradation in a gas-phase sequencing system.

PMID- 11594459
TI  - Signaling by CD40 and its mimics in B cell activation.
AB  - CD40 is a member of the growing tumor necrosis factor receptor (TNF-R) family of
      molecules, and has been shown to play important roles in T cell-mediated B
      lymphocyte activation. Ligation of B cell CD40 by CD154 expressed on activated T
      cells stimulates B cell proliferation, differentiation, isotype switching,
      upregulation of surface molecules contributing to antigen presentation,
      development of the germinal center, and the humoral memory response. Several
      distinct structural motifs in the CD40 cytoplasmic domain regulate various CD40
      signaling pathways, which involve both the TNF-R associated factors (TRAFs) and
      additional signaling proteins, and lead to activation of kinases and
      transcription factors. CD40-mediated B cell activation is mimicked by several
      biological response modifiers, as well as by a viral oncoprotein encoded by the
      Epstein-Barr virus (EBV).

PMID- 11594461
TI  - Reduced enzymatic activity of glucokinase after affinity labeling: results from
      spectrophotometry and electrospray ionization mass spectrometry.
AB  - Glucokinase catalyzes phosphoryl group transfer from ATP to glucose to form
      glucose-6-phosphate in the first step of cellular metabolism. While the location
      of the ATP-binding site of glucokinase was proposed recently, limited information
      exists on its conformation or the key amino acids involved in substrate binding.
      Affinity labeling with phenylglyoxal is used to probe possible Arg residues
      involved in ATP binding. Electrospray ionization mass spectrometry indicates that
      reaction of purified glucokinase with phenylglyoxal results in as many as six or
      seven sites of modification, suggesting nonspecific modification. However,
      preincubation of glucokinase with glucose followed by reaction with phenylglyoxal
      reveals only two sites of modification. Glucokinase activity assays show that
      enzyme preincubated with glucose possesses residual activity corresponding to the
      fraction of unmodified enzyme observed by mass spectrometry, strongly suggesting
      that glucokinase preincubated with glucose is specifically labeled and
      inactivated upon modification by phenylglyoxal. The data support the existing
      conformational model of glucokinase.

PMID- 11594462
TI  - Purification and properties of extracellular phytase from Bacillus sp. KHU-10.
AB  - Bacillus species producing a thermostable phytase was isolated from soil, boiled
      rice, and mezu (Korean traditinal koji). The activity of phytase increased
      markedly at the late stationary phase. An extracellular phytase from Bacillus sp.
      KHU-10 was purified to homogeneity by acetone precipitation and DEAE-Sepharose
      and phenyl-Sepharose column chromatographies. Its molecular weight was estimated
      to be 46 kDa on gel filtration and 44 kDa on SDS-polyacrylamide gel
      elctrophoresis. Its optimum pH and temperature for phytase activity were pH 6.5
      8.5 and 40 degrees C without 10 mM CaCl2 and pH 6.0-9.5 and 60 degrees C with 10
      mM CaCl2. About 50% of its original activity remained after incubation at 80
      degrees C or 10 min in the presence of 10 mM CaCl2. The enzyme activity was
      fairly stable from pH 6.5 to 10.0. The enzyme had an isoelectric point of 6.8. As
      for substrate specificity, it was very specific for sodium phytate and showed no
      activity on other phosphate esters. The Km value for sodium phytate was 50
      microM. Its activity was inhibited by EDTA and metal ions such as Ba2+, Cd2+,
      Co2+, Cr3+, Cu2+, Hg2+, and Mn2+ ions.

PMID- 11594463
TI  - Oxidative folding of human lysozyme: effects of the loss of two disulfide bonds
      and the introduction of a calcium-binding site.
AB  - Mutant human lysozymes (HLZ) lacking two disulfide bonds were constructed to
      study the importance of each disulfide bond on oxidative refolding. To avoid
      destabilization, a calcium-binding site was introduced. Five of the six species
      of two-disulfide mutants could be obtained with enzymatic activity. Based on the
      information obtained from refolding and unfolding experiments, the order of
      importance in oxidative refolding was found to be as follows: SS2(Cys30-Cys116) >
      SS1(Cys6-Cys128) approximately SS3(Cys65-Cys81) > SS4(Cys77-Cys95). Without SS2,
      these mutants refolded with low efficiency or did not refold at all. The bond SS2
      is located in the interface of B-and D-helices, and a small hydrophobic cluster
      is formed near SS2. This cluster may play an important role in the folding
      process and stabilization, and SS2 may act as a stabilizer through its
      polypeptide linkage. The bond SS2 is the most important disulfide bond for
      oxidative folding of lysozymes.

PMID- 11594464
TI  - Molecular cloning and the cDNA-derived amino acid sequence of Narcissus tazetta
      isolectins.
AB  - Recently several complete cDNAs encoding the Narcissus tazetta lectins (NTL) were
      cloned. The sequence analyses of the cloned DNAs reveal that there are at least
      three unidentical positive clones for NTLs. The primary structure of the three
      NTL clones contains a mature polypeptide consisting of 105 amino acids and a C
      terminal peptide extension beyond the C-terminal amino acids Thr-Gly. There are
      two fixed-position cysteines within the protein domain (amino acids 29 and 52),
      which are probably involved in the disulfide-bond linkage within the molecules to
      confer the secondary structure of the mature lectin. One third of the deduced
      amino acid composition consisted of glycine, leucine, and asparagine. From the
      cDNA-derived amino acid sequences the three NTL clones are not identical and are
      suggested to be isolectins present in N. tazetta var. chinensis. This study
      further confirms the previous isolation of mannose-specific isolectins from
      Chinese daffodil leaves.

PMID- 11594465
TI  - Expression and purification of recombinant hemoglobin I from Lucina pectinata.
AB  - Hemoglobin I (HbI) from Lucina pectinata reacts with hydrogen sulfide to form the
      ferric sulfide complex needed to transport H2S to the bacterial endosymbiont. To
      further study HbI, expression studies of this protein were performed in
      Escherichia coli. This is the first time that the recombinant HbI was produced
      using a recombinant DNA expression system. Hemoglobin I cDNA was amplified and
      cloned into the TOPO-PBAD expression vector, which contains a fusion tag of six
      histidine residues (6XHis tag). Plasmid clone sequence analysis was carried out
      in order to ensure that the insert was in the correct reading frame for proper
      protein expression in E. coli. The expression of recombinant HbI was optimal when
      induced for 5 hr with 0.002% of L-arabinose as detected by Western blot analysis.
      The proto-porphyrin group was inserted into the recombinant HbI. Purification of
      the heme-bound recombinant protein was performed under native conditions by
      affinity chromatography using Ni-NTA and Probond resins. The sodium dithionite
      reduced recombinant protein presented a shift from the Soret band at 413-435 nm,
      indicating the presence of the heme group in the adequate amino acid environment
      of HbI. These results indicate that recombinant HbI from Lucina pectinata can be
      successfully expressed in a prokaryotic system retaining its activity toward
      reduction, oxidation, and ligand binding.

PMID- 11594466
TI  - Two new cysteine endopeptidases obtained from the latex of Araujia hortorum
      fruits.
AB  - Two new endopeptidases were purified to homogeneity from the latex of Araujia
      hortorum fruits by a simple purification procedure involving ultracentrifugation
      and ion exchange chromatography. Molecular weights of araujiain h II and
      araujiain h III were 23,718 and 23546 (mass spectrometry), respectively. The
      isoelectric point of araujiain h II was 8.9, whereas araujiain h III had a pI
      higher than 9.3. Maximum proteolytic activity on caseine was reached at pH 8.0
      9.0 for both endopeptidases, which were irreversibly inhibited by iodoacetate and
      E-64, suggesting they belong to the cysteine protease family. Esterolytic
      activity was determined on N-alpha-CBZ-amino acid-p-nitrophenyl esters, and the
      highest kcat/Km values for the both enzymes were obtained with the glutamine
      derivative. The N-terminal sequences of araujiain h II and araujiain h III showed
      a high degree of homology with other plant cysteine endopeptidases.

PMID- 11594467
TI  - Isolation and amino acid sequence of two new PR-4 proteins from wheat.
AB  - We have purified and characterized two new pathogenesis-related (PR) proteins
      from wheat belonging to the PR-4 family. We named the proteins wheatwin3 and
      wheatwin4 in analogy with the previously characterized wheatwin1 and wheatwin2.
      Their isoelectric points were 7.1 and 8.4, respectively. We determined the
      complete amino acid sequence of both proteins by a rapid approach based on the
      knowledge of the primary structures of the homologous wheatwin1 and wheatwin2.
      Wheatwin3 differs from wheatwin1 in one substitution at position 88, while
      wheatwin4 differs from wheatwin2 in one substitution at position 78. The
      secondary structure and solvent accessibility of these residues were determined
      on the three-dimensional model of wheatwinl. Residue 88 was very accessible and
      was located in a flexible region. Preliminary results indicate that, like
      wheatwin1 and wheatwin2, wheatwin3 and wheatwin4 have antifungal activity.

PMID- 11594468
TI  - Science as the basis for public health decisions in nutrition and food safety in
      Asia.

PMID- 11594469
TI  - The agricultural-industrial partnership for eliminating micronutrient
      malnutrition: the investment bargain of the decade.
AB  - The limitations of conventional approaches to eliminating micronutrient
      deficiencies drives the search for a sustainable paradigm. This manuscript argues
      that the public and private sectors must embark on modernization of the Asian
      food industry and reorientation of the international agricultural research
      complex so that nutritionally enriched essential foods will be affordable and
      accessible to the poor. It is recommended that this partnership take special care
      of the needs of Asian children. The costs of chronic undernutrition, availability
      of cost-effective strategies, and benefits of sustained nutrition improvement to
      individuals, families and nations are reviewed. The roles of food fortification,
      plant breeding and biotechnology, both actual and imminent, are described. The
      paper concludes that a recast Green Revolution directed to dietary quality may be
      the key to enhancing the learning and earning capacity of young Asians of the new
      millenium. No other technology offers as large an opportunity to improve
      lives...at such a low cost and in such a short time..." World Bank (1).

PMID- 11594470
TI  - Macronutrients and health-steps to ameliorating the nutrition transition trap.
AB  - Countries that have made the health transition from a communicable disease base
      to a non-communicable disease base find themselves gripped in an epidemic of
      wealth created diseases mediated by altered macronutrient intakes, energy intakes
      and reduction in physical activity. Avoiding the negative impact of the nutrition
      transition while accepting the positive aspects of the wealth transition can best
      be achieved by focussing on publicising the benefits of a low fat diet in the
      context of an active lifestyle. How this is achieved should reflect ecologically
      sound food production appropriate to national needs. Countries that achieve this
      will be in the best position to capitalize on the reduction in communicable
      disease rates without causing a rise in non-communicable disease rates.

PMID- 11594471
TI  - Energy balance and physical activity.
AB  - The prevalence of obesity is increasing in most parts of the world and becoming
      one of the major global public health problems. Although the components of energy
      balance have not been adequately estimated over time, available evidence suggests
      that the increase in obesity is the result of reduced physical activity.
      Increases in physical activity have been shown to be strongly associated with
      improving physical fitness and body composition, with probably a positive effect
      on resting metabolic rate. The Surgeon General's Report on Physical Activity and
      Health advocates that 30 min of regular, moderate-intensity physical activity is
      associated with decreases in the risk of chronic diseases and may contribute to
      quality of life. However, the small changes that contribute 10 min for 3 times a
      day for aerobic training, or one set instead of three sets of repetitions on
      resistance training will provide individuals with health benefits. Indeed,
      nutrition and physical activity should be considered an integral part of fitness
      and good health, and should be encouraged in all age groups, particularly early
      in life. The question is no longer centered around the health benefit of
      increasing physical activity, but rather creating self awareness and behavior
      changes in individuals. Hence, effective intervention programs are needed that
      foster long term changes in physical activity. Among various interventions, the
      Nutrifit program was recently conducted in Thailand and found to improve health
      related fitness in children. The development of more effective interventions and
      approaches is a major challenge in this field today.

PMID- 11594472
TI  - Codex as the basis for national standards and international harmonization.

PMID- 11594473
TI  - Practical approaches to risk assessment.
AB  - The importance of using risk assessment in developing food regulations is growing
      with the globalization of our food supply. The World Trade Organization has
      entrenched the principles of science-based risk assessment in the Agreement on
      Sanitary and Phytosanitary Measures. The relevant international organization for
      food standards, the Codex Alimentarius Commission, recognises risk analysis, and
      its component parts risk assessment, risk management and risk communication, as
      the basis for scientific decision-making. Risk assessment comprises two
      activities: hazard evaluation; and exposure estimation. A hazard may be chemical,
      microbiological or nutritional in origin. The practical application of risk
      assessment in Australia is illustrated in this presentation by four examples
      involving: (1) food additives, (2) microbiological safety of imported raw milk
      cheeses, (3) genetically modified foods and (4) imported food inspection.

PMID- 11594474
TI  - The role of science in Codex standards.
AB  - The key principle in the development of Codex standards is to ensure that the
      decision-making process is based on sound science. The approval for the use of
      food additives and other chemicals in foods should be made only when adequate
      scientific data is available. The same principle applies to the development of
      maximum tolerable (or residue) levels for contaminants in foods. Using the
      General Standards for Contaminants and Toxins in Foods as an example, the
      following criteria are considered, when developing recommendations and standards:
      Toxicological information; Analytical data; Intake data; Fair trade
      considerations; Technological considerations; and Risk assessment and risk
      management considerations. The Codex Alimentarius Commission has repeatedly
      emphasized the use of risk analysis approach, in particular the use of risk
      assessment in conducting the safety evaluation of food additives agricultural and
      veterinary chemicals and environmental and industrial contaminants in foods. In
      this respect, the well known efforts of the FAO/WHO Joint Expert Committee on
      Food Additives (JECFA) and the FAD/WHO Joint Meeting on Pesticide Residues (JMPR)
      provide the much needed information and recommendations for the risk assessment
      of specific chemicals. The risk assessment approach is also used in the safety
      evaluation of foods derived from modern biotechnology as well as in the
      quantitative assessment of microbiological risks in foods.

PMID- 11594475
TI  - Translating Codex guidelines into application.

PMID- 11594476
TI  - Risk management-an industry approach.
AB  - An effective risk management system covering the whole process of food production
      from "farm to fork" is required by the food industry in order to assure that the
      food provided to consumers is safe. Food safety and quality assurance begins with
      the design and development of food products starting with product
      conceptualisation and continuing with the selection, purchasing, and evaluation
      of raw materials and with the specifications for processing, packaging and
      distribution. Within a larger quality management framework a number of tools have
      been developed by the food industry, which when used in an integrated fashion
      facilitate the management of food safety. These include good manufacturing
      practice (GMP), good hygiene practice (GHP) and HACCP (hazard analysis critical
      control point) as well as quality systems which allow the verification that all
      factors affecting the safety of a product are under control. Finally, regulations
      and systems can only function if they are applied. Everyone, from the farmer, the
      line operator in the manufacturing plant, to the person handling the food in
      distribution and sales, needs to be aware of his influence with regards safety.
      The effectiveness of safety awareness programs specific to each area is key to an
      industry approach to risk management.

PMID- 11594477
TI  - Biotechnology--updates and new developments.
AB  - Areas of priority for intensive discovery would be the agbiotechnology and
      biomedical sectors using gene technology as a platform. The use of genetic
      manipulation in farming and the use of plants as 'pharma' factories to
      manufacture therapeutics would be on the rise. The human genome will continue to
      have a powerful impact on research and development of human diseases and
      healthcare. Discovery of genetics and pharmacogenomics will have great impact on
      drug development and will allow the prediction of the patient' s response to
      various drugs as well as the onset of individualised or 'designer drugs'. Human
      stem cells could have their cellular clocks reset by the cloning process,
      enhancing opportunities to grow young cells, tissues and organs for an aging
      population. The cellular clock could also be reset by therapeutic cloning.
      Bioinformatics would be a technology which would be synonymous with
      biotechnology. The analyses of biotechnology research would be conducted in
      silico and would involve the exchange of information among sophisticated computer
      databases. Applications of biotechnology would be even more evident in
      environmental technology, food development and food processing. In electronics,
      the use of the specificity of proteins in biochips is underway. In tandem with
      the explosions in research, regulatory issues, legislation and intellectual
      property rights will evolve to enhance the climate of discovery and innovation.
      Public education will have to be continually enhanced as awareness could negate
      any fear resulting from novel and innovative improvements from biotechnology.

PMID- 11594478
TI  - Modern biotechnology-current standards in Japan.

PMID- 11594479
TI  - Emerging food-borne pathogens.
AB  - The epidemiology of foodborne diseases is changing. While in many developing
      nations the efficient treatment of diarrhoeal diseases through oral rehydration
      has probably led to the prevention of many food related deaths, the underlying
      problems have not been solved. In these countries, the disease incidence of food
      and waterborne disease is still increasing, and now data from other parts of the
      world indicate that new foodborne pathogens have emerged as important public
      health problems. Over the last two decades, bacterial infections caused by
      Campylobacter and enterohaemorrhagic Escherichia coli have emerged, well
      recognized pathogens, such as Salmonella eoteritidis, have increased dramatically
      in disease incidence and important foodborne pathogens have become increasingly
      resistant to antimicrobial agents. The future strategy for prevention of
      foodborne disease should be founded in scientifically based evaluations of the
      whole food production chain 'from farm to table', including a description of the
      most important (risk) factors. Epidemiological studies of outbreaks as well as
      sporadic cases should be aimed at a better understanding of these factors. In
      terms of public health importance of the problem, the focus should be on the size
      of the problem, and the potential for improvement. The indications are that both
      in developed and developing countries there is significant potential for an
      improvement of the situation. With this aim in mind, international effort should
      focus on scientific assessments of the potential for risk reduction under
      different regional conditions.

PMID- 11594480
TI  - The magnitude and trends of under- and over-nutrition in Asian countries.
AB  - In order to understand the magnitude and trends of both under- and over-nutrition
      problems in Asian countries, we reviewed data available in a number of selected
      countries. In general, the prevalence of under-nutrition is declining in this
      region but is still heavy in many countries. The trends varied with complexity of
      individual countries. In China, the prevalence of underweight, stunting and
      wasting was 21.6%, 30.5% and 2.6% in children of 0-4 years old (90,662 subjects,
      1987) . Another large-scale survey in 1992 (176,976 subjects) presented a
      prevalence of 17.1% , 33.5% and 4.5%, respectively. Recent studies showed a
      remarkable improvement in both underweight and stunting. The National Student
      Survey in 1995, however, showed that the prevalence of under-nutrition was 26.9%
      for schoolboys and 38.3% for schoolgirls (7-18 yr). There was an increase of 4.7%
      and 3 .5%, respectively, compared with the results of a similar survey conducted
      in 1985. The proportion of malnutrition in Chinese adults (BMI < 18.5) was 11.6%
      in 1982 and 9.0% in 1992 for urban areas, and 12.9% and 8.0% for rural areas,
      indicating a descending trend over the 10 years. The prevalence of underweight
      was the highest, over 50% among children below 6 years old, in both Bangladesh
      and India, between 50% and 20% in Malaysia, the Philippines, Thailand and
      Vietnam, and below 20% in Mongolia, Kazakhstan and Fiji. It showed a declining
      trend from the 1970s to the 1990s with an average annual reduction of 0.8 to 1.9
      percentage points in these countries. The problem of over-nutrition is emerging
      quickly in this region, not only in some better-off countries but also in
      countries in economy transition. In China, the prevalence of overweight and
      obesity in young adults (BMI > 25) was increased from 9.7% to 14.9% for urban
      areas and from 6.15% to 8.4% for rural areas in a 10-year period (1982 - 1992),
      and the prevalence of overweight jumped from 3.38% and 2.75% in 1985 to 7.18% and
      8.65% in 1995 for schoolboys and schoolgirls. In India, the increase of
      overweight and obesity in female adults was 5.0 percentage points from 1989 to
      1994. The prevalence of overweight was 24.5% for male and 21.4% for female in
      Japan (1995), and 28.7% and 26.0% in Malaysia (1990). These results indicate that
      over-nutrition is a growing problem in this region. Many Asian countries are
      facing double challenges. They have to deal with both under-nutrition and over
      nutrition problems. Among many possible interventions, the further strengthening
      mass education on healthy diet practice should be emphasized.

PMID- 11594481
TI  - Better use of data to define nutrition priority and action.
AB  - Nutrition and dietary survey data has been useful in defining the magnitude of
      malnutrition and dietary deficit. Such information has been helpful in gaining
      attention to support or to do more to improve nutrition-advocacy. However, there
      are also greater opportunities to use the common data to guide the program
      action. In summary, we have plenty of good nutrition and dietary information
      available to us in the planning and operation of nutrition intervention program.
      If we go beyond the use of data to justify area or subject of engagement, we can
      also use the same data for more efficient and more effective program without
      additional cost to us.

PMID- 11594482
TI  - Perspectives on nutrition needs for the new millennium for South Asian regions.
AB  - South Asia is the most populated region of the world with several nutritional
      challenges. Though per capita food energy supply, child survival and life
      expectancy have improved, and even today large segments of the population are
      below the poverty line with high infant and maternal mortality rates. It is
      important to recognize the crucial role of nutrition throughout the life cycle
      from conception to old age. It is very necessary now to move from food security
      to nutrition security and improve the quality of foods both in macro- and
      micronutrients in order to break the transgenerational effects of malnutrition.
      The key solutions to the problems should address the issue of social development,
      population stabilization, environmental degradation and inadequate health and
      nutritional services. Strategies for empowering women and actuating community
      participation as sustainable programmes for human development, measures to reduce
      underweight and stunting in children and prevention of micronutrient malnutrition
      across the population are required. Enhancing food and nutrition security through
      innovative diversified agriculture and dietary practices, prevention and control
      of infection, promotion of food safety and fortification of staples with
      appropriate attention on emerging chronic disorders are essential. Population
      control measures to stabilize the fertility rates, biotechnological approaches
      for genetically modified foods, nutrition surveillance based on assessment,
      analysis and action to address the logistic, technical and compliance issues with
      emphasis on promotion of breast feeding and complementary foods with adequate
      attention on the reproductive needs of adolescent girls, pregnant mothers and
      lactating women would eliminate low birth weight, stunting, and chronic energy
      deficiency in vulnerable groups. Focused studies on bioavailability of
      micronutrients and its enhancement, innovative horticulture interventions,
      fortifications, social marketing strategies would promote the intake of
      micronutrient and phytonutrient rich foods. In-depth epidemiological research, an
      insight into foetal origins of adult disease and nutrition-genes interaction and
      life style alterations will avert the emerging epidemic of chronic diet related
      disorders. An investment in preventing foetal malnutrition improves nutrition of
      women in reproductive age, infant and child nutrition and prevents the onset of
      chronic disease in adult life. Human resource development, IEC measures,
      technology transfer, operational and logistic research, building of databases,
      integrated, intersectoral, multidisciplinary plans and sound management
      information system and surveillance with net working and experience sharing in
      the region will help to overcome the common challenges and lay the foundation for
      a better scenario in these regions in the near future.

PMID- 11594483
TI  - Southeast Asian perspectives on nutrition needs for the new millennium.
AB  - Over the last three decades, there has been significant changes in the lifestyles
      of commmunities, including food habits, and food purchasing and consumption
      patterns in the Southeast Asian region. As a result, there is a definite change
      in the food and nutrition issues in the region. Nutritional deficiencies in many
      of these countries are slowly being decreased in magnitude. On the other hand,
      the significant proportions of the population are now faced with the other facet
      of the malnutrition problem, namely diet-related chronic diseases. However,
      because of the different stages of socio-economic development, the extent of each
      of these extremes of the malnutrition problems varies considerably between the
      different countries in Southeast Asia. Nutrition needs in the new millennium
      would necessarily differ somewhat among these countries while at the same time,
      there would be a considerable amount of similarities. This presentation
      highlights several macro issues that countries in the region may focus on in the
      near future. Various intervention programmes have been undertaken by authorities
      to tackle the co-existence of twin faces of malnutrition in many developing
      countries. It would be desirable to have a blue print of such programmes and
      activities in the National Plans of Action for Nutrition (NPANs) . The NPAN
      should be more than a framework or a descriptive document. It should be a tool
      for action, an operational plan that sets out priorities; identifies projects and
      activities, with details of implementation such as what, how and when; designates
      responsibilities and accountability for the activities; identifies resource
      requirements and their source; and sets out the plan for monitoring and
      evaluation. One of the main obstacles in the formulation and effective
      implementation of intervention programmes in developing countries is the lack of
      comprehensive data on the extent of the problems in many cases and the causes of
      such problems specificy to the communities concerned. It is thus imperative to
      identify appropriate research priorities and conduct relevant studies. It is also
      important to have basic baseline data collected at regular intervals such as
      nutritional status of communities and dietary intake. To conduct all these
      activities, it is vital to ensure adequate funding, preferably through
      establishing a dedicated fund for research. There should be closer collaboration
      between countries in the region in all nutrition activities to enable sharing of
      resources, experiences and learn from the mistakes of others. One existing
      mechanism is through the ASEAN structure. The other existing mechanisms are
      through WHO and FAO. One other mechanism is through the International Life
      Sciences Institute (ILSI) Southeast Asian Branch. Closely related to this need
      for networking is the need for continuing harmonization of approaches to
      nutrition activities in the region. Current efforts in harmonisation include RDA,
      nutritional status assessment methodologies and dietary guidelines. Other areas
      of harmonisation in the near future include nutrition labelling and claims.

PMID- 11594484
TI  - Japanese perspectives on nutrition for new millenium.

PMID- 11594485
TI  - Abbreviated report of the WHO Western Pacific Region Workshop on National Plans
      of Action for Nutrition: key elements for success, constraints and future plans.
AB  - A workshop on National Plans of Action for Nutrition: Constraints, Key Elements
      for Success, and Future Plans was convened and organized by the WHO Regional
      Office for the Western Pacific in collaboration with the Institute for Medical
      Research Malaysia and co-sponsored with FAO and UNICEF from 25-29 October 1999.
      It was attended by representatives of 25 countries in the region and resource
      persons, representatives from WHO and other international agencies. The
      objectives of the workshop were to review the progress of countries in
      developing, implementing and monitoring national plans of action for nutrition
      (NPANs) in the Western Pacific Region and to identify constraints and key
      elements of success in these efforts. Most of the countries have NPANs, either
      approved and implemented or awaiting official endorsement. The Plan formulation
      is usually multisectotal, involving several government ministries, non
      governmental organizations, and international agencies. Often official adoption
      or endorsement of the Plan comes from the head of state and cabinet or the
      minister of health, one to six years from the start of its formulation. The NPAN
      has stimulated support for the development and implementation of nutrition
      projects and activities, with comparatively greater involvement of and more
      support from government ministries, UN agencies and non-governmental agencies
      compared to local communities, bilateral and private sectors and research and
      academic institutions. Monitoring and evaluation are important components of
      NPANs. They are, however, not given high priority and often not built into the
      plan. The role of an intersectoral coordinating body is considered crucial to a
      country's nutrition program. Most countries have an intersectoral structure or
      coordinating body to ensure the proper implementation, monitoring and evaluation
      of their NPANs. The workshop identified the constraints and key elements of
      success in each of the four stages of the NPAN process: development,
      operationalization, implementation, and monitoring and evaluation. Constraints to
      the NPAN process relate to the political and socioeconomic environment, resource
      scarcity, control and management processes, and factors related to
      sustainability. The group's review of NPAN identified successful NPANs as those
      based on recent, adequate and good quality information on the nutritional
      situation of the country, and on the selection of strategies, priorities and
      interventions that are relevant to the country and backed up by adequate
      resources. Continued high level political commitment, a multisectoral approach,
      and adequate participation of local communities are other key elements for
      success. The participants agreed on future actions and support needed from
      various sources for the further development, implementation, monitoring and
      evaluation of their NPANs. The recommendations for future actions were
      categorized into actions pertaining to countries with working NPAN, actions for
      countries without working NPAN and actions relevant to all countries. There was
      also a set of suggested actions at the regional level, such as holding of regular
      regional NPAN evaluation meetings, inclusion of NPAN on the agenda of regional
      fora by the regional organizations, and strengthening of regional nutrition
      networks.

PMID- 11594486
TI  - Combating micronutrient deficiencies--an important component of poverty
      reduction.
AB  - In the late 1990s, the international development banks and the International
      Monetary Fund (IMF) convened to outline seven International Development Goals
      (IDGs) to reduce poverty by 2015. These goals incorporated both the economic and
      social dimensions of poverty. A two-thirds reduction of child mortality and a
      three-fourths reduction of maternal mortality from rates in 1990 by 2015 are two
      of these seven IDGs. There is a need for better combinations of cost-effective
      strategies to reach these challenging goals by the year 2015. This paper
      discusses the potential usefulness of micronutrient deficiency control programs
      for this purpose.

PMID- 11594487
TI  - Fortification challenges and needs.
AB  - Experience in many parts of the developing world has shown that food
      fortification offers a cost-effective and sustainable solution to the problem of
      micronutrient malnutrition. Building on the advances in science and technology
      and backed by studies on the economic benefits of fortification programs,
      governments and industry are beginning to respond positively to the call of
      nutrition advocates to adopt fortification as a long-term strategy. On the other
      hand, formidable challenges still remain in many countries in Asia, constraining
      the widespread adoption of this strategy. The science and technology community
      needs to provide adequate scientific and technological information as basis for
      planning and decision making. The government faces the challenge of providing the
      enabling environment for all stakeholders to cooperate in the fortification
      effort. Industry faces the challenge of adapting its production system to the
      requirements of fortification in order that they can contribute to social
      objectives while pursuing their economic objectives. The international and
      bilateral aid agencies need to seek tried and innovative ways to support the
      multiple players of food fortification, as these players in turn face the
      challenges that confront them.

PMID- 11594488
TI  - Opening remarks. Third Asian Conference on Food Safety and Nutrition October 3,
      2000, Beijing, China.

PMID- 11594489
TI  - Welcome address. Third Asian Conference on Food Safety and Nutrition October 3,
      2000, Beijing, China.

PMID- 11594490
TI  - Distinguishing logic from association in the solution of an invisible
      displacement task by children (Homo sapiens) and dogs (Canis familiaris): using
      negation of disjunction.
AB  - Prior research on the ability to solve the Piagetian invisible displacement task
      has focused on prerequisite representational capacity. This study examines the
      additional prerequisite of deduction. As in other tasks (e.g., conservation and
      transitivity), it is difficult to distinguish between behavior that reflects
      logical inference from behavior that reflects associative generalization. Using
      the role of negation in logic whereby negative feedback about one belief
      increases the certainty of another (e.g., a disjunctive syllogism), task-naive
      dogs (Canis familiaris; n=19) and 4- to 6-year-old children (Homo sapiens; n=24)
      were given a task wherein a desirable object was shown to have disappeared from a
      container after it had passed behind 3 separate screens. As predicted, children
      (as per logic of negated disjunction) tended to increase their speed of checking
      the 3rd screen after failing to find the object behind the first 2 screens,
      whereas dogs (as per associative extinction) tended to significantly decrease
      their speed of checking the 3rd screen after failing to find the object behind
      the first 2 screens.

PMID- 11594492
TI  - Amount of prenatal visual stimulation alters incubation times and postnatal
      preferences in leopard geckos (Eublepharis macularius).
AB  - The authors exposed gecko (Eublepharis macularius) embryos to patterned visual
      stimulation beginning at either 1 week or 2 weeks prior to hatching. Embryos
      exposed to the substantially augmented amount of prenatal visual stimulation
      hatched significantly earlier than the embryos either exposed to the moderately
      augmented prenatal visual stimulation or not exposed to any prenatal visual
      stimulation (p < .01). Hatchling mass was not affected. Embryos exposed to
      substantially augmented visual stimulation demonstrated a postnatal preference
      for patterned light in a simultaneous choice test at 24 hr of age (p < .01).
      Control embryos demonstrated a preference for normal light conditions (p < .01),
      whereas experimental embryos exposed to lesser amounts of prenatal visual
      stimulation did not show a preference for either stimulus. At 1 week of age,
      geckos in all conditions failed to exhibit a preference for either stimulus.

PMID- 11594491
TI  - Cardiac responses to acoustic playback experiments in the captive bottlenose
      dolphin (Tursiops truncatus).
AB  - Acoustic recordings were used to investigate the cardiac responses of a captive
      dolphin (Tursiops truncatus) to sound playback stimuli. A suction-cup hydrophone
      placed on the ventral midline of the dolphin produced a continuous heartbeat
      signal while the dolphin was submerged. Heartbeats were timed by applying a
      matched-filter to the phonocardiogram. Significant heart rate accelerations were
      observed in response to playback stimuli involving conspecific vocalizations
      compared with baseline rates or tank noise playbacks. This method documents that
      objective psychophysiological measures can be obtained for physically
      unrestrained cetaceans. In addition, the results are the 1st to show cardiac
      responses to acoustic stimuli from a cetacean at depth. Preliminary evidence
      suggests that the cardiac response patterns of dolphins are consistent with the
      physiological defense and startle responses in terrestrial mammals and birds.

PMID- 11594493
TI  - How golden hamsters (Mesocricetus auratus) discriminate top from bottom flank
      scents in over-marks.
AB  - Using a habituation-discrimination paradigm, the authors investigated what cues
      male golden hamsters (Mesocricetus auratus) use to determine the top and bottom
      positions in flank gland over-marks. A difference in the ages of 2 hamsters'
      marks did not, by itself, produce differential memory or evaluation of the 2
      scents. A spatial configuration of marks suggestive of an overlap was sufficient
      for the apparently overlapping scent to be remembered or valued more than the
      apparently underlying scent. Cues from the overlap of 2 hamsters' marks were also
      sufficient. These results, consistent with those previously found for responses
      to hamster vaginal scent over-marks, suggest that hamsters use similar cues to
      analyze scent over-marks that are different in chemical composition and in social
      functions.

PMID- 11594494
TI  - Spontaneous representation of number in cotton-top tamarins (Saguinus oedipus).
AB  - The "violation of expectancy" looking-time methodology has proven a powerful tool
      for exploring prelinguistic mental representations in human infants as well as in
      nonhuman primates. Four studies applying this methodology to the question of
      spontaneous number representations in cotton-top tamarins (Saguinus oedipus) are
      reported here. Monkeys were shown 1 + 1 events in which objects were placed
      behind a screen, 1 by 1. The screen was removed, revealing consistent (2 objects)
      and inconsistent (1, 3, or 1 large object twice the mass of original object)
      outcomes. In all studies, monkeys looked longer at the inconsistent than at the
      consistent outcome. When the monkeys view a 1 + 1 operation, they expect exactly
      2 objects. It is likely that these numerical representations are spontaneously
      available to a variety of primate species and could provide a foundation on which
      humans' number sense was constructed over evolution and development.

PMID- 11594495
TI  - The production and perception of long calls by cotton-top tamarins (Saguinus
      oedipus): acoustic analyses and playback experiments.
AB  - The authors' goal was to provide a better understanding of the relationship
      between vocal production and perception in nonhuman primate communication. To
      this end, the authors examined the cotton-top tamarin's (Saguinus oedipus)
      combination long call (CLC). In Part 1 of this study, the authors carried out a
      series of acoustic analyses designed to determine the kind of information
      potentially encoded in the tamarin's CLC. Using factorial analyses of variance
      and multiple discriminant analyses, the authors explored whether the CLC encodes
      3 types of identity information: individual, sex, and social group. Results
      revealed that exemplars could be reliably assigned to these 3 functional classes
      on the basis of a suite of spectrotemporal features. In Part 2 of this study, the
      authors used a series of habituation-dishabituation playback experiments to test
      whether tamarins attend to the encoded information about individual identity. The
      authors 1st tested for individual discrimination when tamarins were habituated to
      a series of calls from 1 tamarin and then played back a test call from a novel
      tamarin; both opposite- and same-sex pairings were tested. Results showed that
      tamarins dishabituated when caller identity changed but transferred habituation
      when caller identity was held constant and a new exemplar was played (control
      condition). Follow-up playback experiments revealed an asymmetry between the
      authors' acoustic analyses of individual identity and the tamarins' capacity to
      discriminate among vocal signatures; whereas all colony members have distinctive
      vocal signatures, we found that not all tamarins were equally discriminable based
      on the habituation-dishabituation paradigm.

PMID- 11594496
TI  - Imitative learning by captive western lowland gorillas (Gorilla gorilla gorilla)
      in a simulated food-processing task.
AB  - Although field studies have suggested the existence of cultural transmission of
      foraging techniques in primates, identification of transmission mechanisms has
      remained elusive. To test experimentally for evidence of imitation in the current
      study, we exposed gorillas (Gorilla gorilla gorilla) to an artificial fruit
      foraging task designed by A. Whiten and D. M. Custance (1996). Gorillas (n=6)
      watched a human model remove a series of 3 defenses around a fruit. Each of the
      defenses was removed using 1 of 2 alternative techniques. Subsequent video
      analysis of gorillas' behavior showed a significant tendency to copy the observed
      technique on 1 of the individual defenses and the direction of removal on another
      defense. This is the first statistically reliable evidence of imitation in
      gorillas. Sequence of defense removal was not replicated. The gorillas' responses
      were most similar to those of chimpanzees.

PMID- 11594497
TI  - Training squirrel monkeys (Saimiri sciureus) to deceive: acquisition and analysis
      of behavior toward cooperative and competitive trainers.
AB  - Three squirrel monkeys (Saimiri sciureus) learned to reach toward a container
      that covered food if a cooperative trainer rewarded such reaches by giving the
      food. A competitive trainer kept any food found, but wrong selections by this
      trainer were also rewarded. The monkeys initially reached toward the baited
      container indiscriminately, but gradually and with the aid of color-cued
      containers, all 3 reliably reached "honestly" and "deceptively" in the presence
      of the cooperative and competitive trainers, respectively. The monkeys did not
      appear to take the trainers' knowledge about the location of the food into
      account, and deception did not occur if food was placed under the normally
      unbaited container. With additional containers present, monkeys misled the
      competitive trainer into selecting the unbaited container farthest from the
      baited one. Although not indicative of mental attribution, the monkeys' behavior
      suggests awareness of the acquired communicative function of the reaching
      response.

PMID- 11594498
TI  - The use of bouts and frequencies in the evaluation of hand preferences for a
      coordinated bimanual task in chimpanzees (Pan troglodytes): an empirical study
      comparing two different indices of laterality.
AB  - Hand preferences for a coordinated bimanual task were assessed in 109 chimpanzees
      (Pan troglodytes). Hand preference was evaluated for 4 test sessions using bouts
      and frequencies of hand use to compare the sensitivity of each level of analysis
      in evaluating individual variation in handedness. Overall, significant population
      level right-handedness was found using several different measures of hand use.
      Handedness indices based on bouts and frequencies were highly and significantly
      correlated. Moreover, hand preferences were consistent across tests despite
      efforts to situationally bias preference during each test. Taken together, these
      data do not support the view that bouts are a better level of analysis for
      evaluating hand preference. The results further suggest that hand preferences for
      coordinated bimanual actions are not influenced by situational factors and may
      reflect an inherent specialization of the left hemisphere for motor skill.

PMID- 11594499
TI  - The effect of response contingencies on scale model task performance by
      chimpanzees (Pan troglodytes).
AB  - The effects of modified procedures on chimpanzees' (Pan troglodytes) performance
      in a scale model comprehension task were examined. Seven chimpanzees that
      previously participated in a task in which they searched an enclosure for a
      hidden item after watching an experimenter hide a miniature item in the analogous
      location in a scale model were retested under procedures incorporating response
      costs. In Experiment 1, chimpanzees were trained under procedures that rewarded
      only item retrievals occurring on the 1st search attempt. During test trials, 6
      chimpanzees performed above chance, including 4 that were previously unsuccessful
      under the original procedures (V. A. Kuhlmeier, S. T. Boysen, & K. L. Mukobi,
      1999). Experiment 2 compared performance under the new and original procedures.
      Results indicated that for some chimpanzees, performance depended on procedures
      that decreased the use of competing search strategies and encouraged strategies
      based on information from the scale model.

PMID- 11594500
TI  - Habituation and sensitization of aggression in bullfrogs (Rana catesbeiana):
      testing the dual-process theory of habituation.
AB  - The aggressive response of male bullfrogs (Rana catesbeiana) habituates with
      repeated broadcasts of acoustic stimuli simulating a new territorial neighbor.
      The effects of stimulus repetition rate and stimulus intensity on bullfrog
      aggressive responses were tested in a field experiment designed to test the
      assumptions of a dual-process theory of habituation. Synthetic advertisement
      calls were broadcast at 2 repetition rates and 2 intensities in a factorial
      design. Bullfrogs were more aggressive at the higher stimulus intensity at both
      repetition rates. Aggressive responses habituated more slowly at the higher
      stimulus intensity and slower repetition rate compared with other treatments.
      Several biotic and abiotic factors had small or negligible effects on aggressive
      responses. Although consistent with the operation of 2 opposing processes,
      habituation and sensitization, the data provide only partial support for the
      assumptions of dual-process theory.

PMID- 11594501
TI  - Use of cue configuration geometry for spatial orientation in human infants (Homo
      sapiens).
AB  - Research with both rats and human infants has found that after inertial
      disorientation, the geometry of an enclosed environment is used in preference
      over distinctive featural information during goal localization. Infants (Homo
      sapiens, 18-24 months) were presented with a toy search task involving inertial
      disorientation in 1 of 2 conditions. In the identical condition, 4 identical
      hiding boxes in a rectangular formation were set within a circular enclosure. In
      the distinctive condition, 4 distinctive hiding boxes were used. Infants searched
      the goal box and its rotational equivalent significantly more than would be
      expected by chance in the identical condition, showing that they were sensitive
      to the geometric configuration of the array of boxes. Unlike the results of
      studies using a rectangular enclosure, however, in the distinctive condition,
      infants searched at the correct location significantly more than at other
      locations.

PMID- 11594502
TI  - Neonatal tumors of the CNS: a report of 9 cases and a review.
AB  - Neonatal central nervous system (CNS) tumors are an uncommon and histologically
      heterogeneous group of neoplasms with different clinical and biological features
      from those arising in childhood. We report 9 cases in which a diagnosis of CNS
      tumor was confirmed by biopsy or autopsy during the years 1982-1997 in the Vall
      d'Hebron Children's Hospital, Barcelona. Two cases were fetal tumors detected by
      fetal sonography, 3 patients were symptomatic in the first days after birth and 4
      patients presented initial clinical signs in the first weeks or months of life.
      Eight lesions were supratentorial and 1 was located in the spinal cord. According
      to histologic types, there were 2 glioneuronal tumors, 1 anaplastic astrocytoma,
      1 choroid plexus carcinoma, 1 immature teratoma, 1 craniopharyngioma, 1
      hemangioblastoma, 1 astroblastoma and 1 hemangioendothelioma. Extensive review of
      the literature indicates that our cases of hemangioblastoma, astroblastoma and
      hemangioendothelioma are exceptional and one more of the very rare and isolated
      previously published cases.

PMID- 11594503
TI  - Comparative investigation of proliferation markers and their prognostic relevance
      in human meningiomas.
AB  - OBJECTIVE: In human meningiomas, histology alone does not always predict the
      clinical outcome. Proliferative activity has therefore, become a potential tool
      in the histopathological grading of these tumors. The aim of this study was to
      investigate different Ki67 antibodies on meningiomas, to compare their
      proliferation indices (PI) and with other proliferation markers, such as S-phase
      fraction and mitotic activity, and to see whether these factors correlate with
      histological tumor grade. MATERIAL AND METHODS: The study included 43 meningiomas
      graded according to the criteria of WHO and Jaaskelainen et al. [1985, 1986].
      Paraffin sections were used for immunohistochemical detection of Ki67 antigen and
      flow-cytometric determination of S-phase fraction. RESULTS: The PIs displayed an
      overall increase with increasing histological grade, however, the range of values
      for benign, atypical and anaplastic meningiomas were wide, resulting in
      considerable overlap between the groups. There were for the most significant
      correlations between the different proliferation markers. CONCLUSIONS: Ki67
      equivalent antibodies and S phase fraction have no advantage over counting
      mitoses to assess the proliferative activity in meningiomas. Thus, mitotic
      activity justifies its role in meningioma grading.

PMID- 11594504
TI  - Late onset and very mild course of Xp21 Becker type muscular dystrophy.
AB  - We report a case of late onset of Becker's muscular dystrophy (BMD), diagnosed at
      the age of 60, which showed a very mild clinical course. Remarkably, the
      immunohistochemical pattern did not show significant alterations, while Western
      blotting disclosed low molecular weight dystrophin. DNA analysis showed a
      deletion of the exons 45-53 of the Xp21 gene, which is fairly typical of Becker's
      muscular dystrophy but not predictable of clinical course. The possibility of
      Xp21 muscular dystrophy must be considered in all myopathies of uncertain cause,
      also in elderly patients.

PMID- 11594505
TI  - The giant axonal neuropathy--clinical and hisotological aspects, differential
      diagnosis and a new case.
AB  - The giant axonal neuropathy (GAN) is morphologically characterized by axonal
      swellings and accumulations of neurofilaments in giant axons and other cell
      types. Curly hair is not a constant finding. The clinical course is progressive
      and mostly starts in early childhood. We report the case of a boy aged 6 years at
      the time of sural nerve and muscle biopsy. Suralis nerve showed a reduced
      numerical density of myelinated fibres with a consecutive endoneural fibrosis.
      Morphometric investigation revealed a pronounced reduction of fibres measuring 8
      12 microm in diameter. Giant axons were seen in relatively low number and were
      not very large with a maximum diameter of 18 microm. They had a relatively thin
      myelin sheet proved also by the high G ratio in the histogram. Many onion bulb
      formations of Schwann cells were present. There are only few reports of giant
      axons with such low maximum diameter in cases with GAN, the lowest maximum
      diameters being reported in case reports on Japanese children. Up to now, this is
      the first report of a non-Japanese patient with a low maximum diameter of giant
      axons of less than 20 microm in peripheral nerve biopsy. Ultrastructurally,
      typical accumulations of neurofilaments and osmiophilic aggregates were found in
      giant axons. Other diagnoses with occurrence of giant axons could be excluded in
      view of the absence of specific findings. Sporadic or familial cases with giant
      axons are discussed. Sceletal muscle biopsy (M. quadriceps femoris) showed
      neurogenic affection with presence of small angulated atrophic muscle fibres.

PMID- 11594506
TI  - Gliosarcoma with areas of primitive neuroepithelial differentiation and
      extracranial metastasis.
AB  - We report a case of gliosarcoma with areas of primitive neuroepithelial
      differentiation arising in the temporal lobe of a 53-year-old man. The
      sarcomatous component of this tumor was perivascular in its distribution and
      showed expression of factor VIII-related antigen, smooth muscle actin and CD34.
      The primitive neuroepithelial component possessed a small cell morphology and
      showed expression of neuronal antigens. Strong expression of p53 was demonstrated
      throughout the tumor with only focal weak expression of epidermal growth factor
      receptor. The tumor developed widespread extraneural metastases 5 months after
      surgical resection of the primary tumor. Histological examination of the liver
      metastases showed them to consist predominantly of the primitive neuroepithelial
      component. We believe this to be a novel pattern of differentiation in a
      gliosarcoma which in this case was associated with an aggressive metastatic
      potential.

PMID- 11594507
TI  - A lateral ventricular gliosarcoma arising in an ependymoma.
AB  - OBJECTIVE: We describe a 29-year-old man with gliosarcoma in the lateral
      ventricle. CASE: The patient presented with headache and impairment of
      consciousness. Computed tomography and magnetic resonance imaging localized the
      tumor to the right lateral ventricle and showed heterogeneous enhancement with
      administration of contrast agents. The tumor was partially removed via a
      transcallosal approach. Histologic examination disclosed gliosarcoma arising by
      malignant transformation of an ependymoma. POST-OPERATIVE COURSE: The patient
      died of tumor progression 78 days after admission, despite intensive radiotherapy
      and chemotherapy.

PMID- 11594508
TI  - Cerebral phaeohyphomycosis caused by a dematiaceous scopulariopsis species.
AB  - This report describes a rapidly fatal case of cerebral phaeohyphomycosis in a 33
      year-old immunocompetent male. The infection presented as a single large lesion
      in the deep white matter of one temporal lobe, which was then removed surgically.
      Histologic features observed in the lobectomy specimen were characterized by
      perivascular sleeves of mononuclear cells accompanied by hemorrhages. These were
      reminiscent of acute hemorrhagic leukoencephalitis except for the presence of
      rare fungal organisms and sparse multinucleated giant cells similar to those
      occurring in AIDS. During the four days following surgery, a large focus of
      cerebritis with massive invasion of fungi developed in each centrum semiovale
      around the ventriculostomy sites. Fungal culture of the brain obtained at autopsy
      grew an organism consistent with a Scopulariopsis species.

PMID- 11594509
TI  - Natural course of lymphocytic infundibuloneurohypophysitis.
AB  - Natural course of lymphocytic infundibuloneurohypophysitis is poorly understood.
      A 49-year-old male had noticed being unnaturally thirsty since about two years
      previously. An enlargement of the pituitary stalk and pituitary gland was thus
      observed by MR at that time. However, no medical care had been given. Two years
      later, he was admitted to our hospital due to headache in addition to
      panhypopituitarism. The histologic features included T cell dominant lymphocytes
      infiltrating prominently the entire pituitary gland with a small amount of
      multinucleated giant cells, focal and small necrosis, cholesterin crystals and
      granuloma. Neither tuberculosis nor Langerhans histiocytosis were observed. In
      addition, the patient was found to have a unique massive well-encapusulated
      lesion in the sphenoid sinus, just below the pituitary fossa, consisting of
      serous fluid, normal columnar epithelium and submucosal fibrosis. This patient
      had a fairly typical clinical manifestation of lymphocytic
      infundibuloneurohypophysitis with invason of the posterior lobe and the stalk.
      The lesion became chronic and leaked to the sphenoid sinus. As a result, chronic
      hypophysitis with granuloma formation thus occurred. This case may show the
      course of this disease if not treated.

PMID- 11594510
TI  - Neutrophil cytoskeletal disease.
AB  - Neutrophils and other phagocytes migrate to the site of infection, ingest
      pathogens, and destroy them after releasing granule contents and active oxygen.
      These activities of the cells are closely associated with a rapid reorganization
      of the cytoskeleton, in which actin polymerizes, cross-links, anchors to the
      membrane and depolymerizes under the control of various actin-associated
      proteins. Defect in actin or its associated proteins results in neutrophil
      cytoskeletal disease where abnormality primarily appears as motility or
      chemotactic defect of the cells. Although their molecular mechanisms have not
      been elucidated, neutrophil actin dysfunction and neutrophil actin dysfunction
      with abnormal 47- and 89-kd proteins have been reported. Recently, abnormal-beta
      actin disease and disease with Rac 2 mutation, both of which accompany neutrophil
      chemotactic dysfunction, were analyzed at the molecular level. These diseases are
      systemic, but neutrophil dysfunction of the patients is remarkable. Here we
      review the literature on diseases due to cytoskeletal abnormality. Many other
      diseases with actin or actin-associated protein dysfunction may be reported in
      the near future.

PMID- 11594511
TI  - Contributions of myeloperoxidase to proinflammatory events: more than an
      antimicrobial system.
AB  - Optimal oxygen-dependent antimicrobial activity of circulating polymorphonuclear
      leukocytes reflects the synergistic effects of the myeloperoxidase (MPO)-hydrogen
      peroxide-halide system. Delivered from its storage compartment to the
      phagolysosome during fusion of the azurophilic granules, MPO catalyzes the
      oxidation of chloride in the presence of H2O2, chemistry unique to MPO, and
      thereby generates an array of highly reactive oxidants. Recent investigations of
      a wide range of inflammatory disorders have identified biochemical markers of MPO
      dependent reactions, thus indirectly implicating MPO in their pathogenesis,
      progression, or perpetuation. The implied involvement of MPO-dependent events in
      diseases such as atherosclerosis forces reexamination of several fundamental
      tenets about MPO that are derived from studies of myeloid cells, most notably
      factors important in the regulated expression of MPO gene transcription. The
      evidence supporting a role for MPO in the pathogenesis of atherosclerosis,
      demyelinating diseases of the central nervous system, and specific cancers is
      reviewed and some of the new questions raised by these studies are discussed.
      Lastly, an appreciation for the existence of a broad family of proteins
      structurally related to MPO and the functional diversity implied by the
      corresponding structures may provide insights into novel ways in which MPO can
      function as more than an important antimicrobial component.

PMID- 11594512
TI  - Neutrophil functions of patients with vasculitis related to myeloperoxidase
      specific anti-neutrophil antibody.
AB  - Neutrophils are hypothesized to cause tissue damage resulting in the development
      of vasculitis and glomerulonephritis, although they are known to primarily take
      part in host defense functions. The infiltration of inflammatory cells. notably
      neutrophils and macrophages, is observed in the progression of vasculitis.
      Neutrophils with activated status and anti-neutrophil cytoplasmic antibodies
      (ANCAs), especially myeloperoxidase-specific (MPO)-ANCA, have been implicated in
      the development of vasculitis. The target molecule of MPG-ANCA is a lysosomal
      enzyme MPO that usually acts to kill bacteria, viruses, and fungi and that causes
      damage to the tissue due to the toxicity of its product, hypochlorite (OCl-). To
      elucidate the role of MPO-ANCA in the progression of vasculitis, a set of MPO
      peptide fragments has been developed, and the corresponding epitope site for the
      specific monoclonal and/or oligoclonal antibody resulting in vasculitis has been
      determined. Recently some mouse models have been used for analyzing the
      correlation between MPO and MPO-ANCA in relation to damage of blood vessels
      followed by the development of vasculitis. This review focuses on the role of
      activated neutrophils in the development of vasculitis associated with MPO-ANCA
      and the target molecules of ANCA. In addition, the reactivities of ANCA and
      inflammatory cytokines involving leukocyte-derived chemotaxin 2 (LECT2) are also
      discussed.

PMID- 11594513
TI  - Treatment of myelodysplastic syndrome with low-dose human granulocyte colony
      stimulating factor: a multicenter study.
AB  - The objective of this study was to determine the hematopoietic effects and
      toxicity of low-dose granulocyte colony-stimulating factor (G-CSF) in
      myelodysplastic syndrome (MDS) patients with neutropenia. Recombinant human G-CSF
      (Lenograstim) was administered by daily subcutaneous injection with an initial
      dosage of 0.5 microg/kg per day for 2 weeks. Patients not responding to the
      initial dosage received the escalated dosage, 1 to 2 microg/kg per day for 2
      weeks. Eligibility criteria were the following: French-American-British disease
      classification subtype refractory anemia (RA), refractory anemia with ringed
      sideroblasts (RARS), or refractory anemia with excess blasts (RAEB) with an
      absolute neutrophil count (ANC) of <1.5 x 10(9)/L. Criteria indicating response
      to treatment were ANC of >1.5 x 10(9)/L and doubling of ANC on at least 2
      occasions. Thirty-two MDS patients were recruited from 6 university hospitals.
      Eighteen patients had RA, 4 had RARS, and 10 had RAEB. Median age was 56.4 years
      (range, 28-87 years). Twenty-six patients (81.2%) had an increase in ANC from a
      median of 0.94+/-0.35 x 10(9)/L to 4.24+/-3.78 x 10(9)/L. Three of 6 patients who
      did not respond to the initial dosage responded to the escalated dosage of 1
      microg/kg per day. Eighteen (81.8%) of 22 patients with RA or RARS responded
      compared with 8 (80%) of 10 patients with RAEB. The response rates in patients
      with ANCs of <0.5 x 10(9)/L. 0.5 to <1.0 x 10(9)/L, and 1.0 to 1.5 x 10(9)/L were
      80%, 70%, and 88.2%, respectively. The side effects were minimal. No significant
      changes in hemoglobin levels or platelet counts were observed. In conclusion, low
      dose G-CSF administered by subcutaneous injection is well tolerated and effective
      in improving neutropenia in MDS patients.

PMID- 11594514
TI  - Expression of p53 and Ki-67 antigen in bone marrow giant proerythroblasts
      associated with human parvovirus B19 infection.
AB  - Giant proerythroblasts are hallmarks of human parvovirus B19 infection. We
      attempted to characterize these cells in 5 patients with parvovirus B19-induced
      pure red cell aplasia using immunostaining of paraffin-embedded bone marrow
      sections with antibodies against erythroid-lineage-specific proteins, viral
      capsid antigen VP-1, and apoptosis- and cell-cycle-related proteins. Giant
      proerythroblasts are immunohistochemically consistent with early erythroid
      precursors of cells in the differentiation stage of CD34-, cytoplasmic spectrin+,
      glycophorin A-, and band-3-. VP-1 was expressed in the nucleus and cytoplasm of
      small- to medium-sized spectrin+ erythroid cells but not in giant
      proerythroblasts. The giant proerythroblasts displayed nuclear staining for p53
      (41%+/-16%) and Ki-67 antigen (100%+/-0%) and cytoplasmic staining for Bax (65%+/
      11%) and procaspase-3 (78%+/-10%), whereas they were not stained for
      p21Wafl/Cip1, active form of caspase-3, or terminal deoxynucleotidyltransferase
      mediated deoxyuridine nick-end labeling (TUNEL). Antiapoptotic proteins, Bcl-2
      and Mcl-1, were not expressed in the giant cells, and Bcl-x was infrequently
      expressed in these cells (11%+/-4%). These immunohistochemical findings suggest
      that giant proerythroblasts are proliferating erythroid precursors with
      accumulation of nonfunctional p53.

PMID- 11594515
TI  - A new glucose-6-phosphate dehydrogenase variant G6PD Sugao (826C-->T) exhibiting
      chronic hemolytic anemia with episodes of hemolytic crisis immediately after
      birth.
AB  - A case of glucose-6-phosphate dehydrogenase (G6PD) deficiency associated with
      chronic hemolysis with episodes of hemolytic crisis immediately after birth is
      reported. The propositus was a 1-month-old Japanese male infant. Molecular
      analysis of the G6PD gene revealed a novel missense mutation (826C-->4T) in exon
      8 predicting a single amino acid substitution, Pro276Ser. The mother was
      confirmed to be heterozygous for this mutation. We designated this novel class 1
      variant as G6PD Sugao. Pro276 is a phylogenetically conserved residue that may
      play a significant role in dimer formation.

PMID- 11594516
TI  - Analysis of 20-year follow-up study of LVP regimen for adult acute lymphoblastic
      leukemia.
AB  - In an attempt to develop a new intensive chemotherapy for adults with untreated
      acute lymphoblastic leukemia (ALL), 3 sequential programs were designed for 62
      patients (age range, 15 to 74 years; median age, 32 years) consisting of the LVP
      79 (1979-1984, 27 patients), LVP-85 (1984-1986, 14 patients), and LVP-87 (1987
      1989, 21 patients) regimens. The influence of clinical and biologic
      characteristics on the patient outcome was also examined. L-asparaginase (L-asp),
      vincristine, and prednisolone, defined collectively as LVP, were administered for
      induction chemotherapy in all protocols. After achieving complete remission (CR),
      patients underwent 2 years of multi-agent consolidation, intensification, and
      maintenance therapy consisting of various combinations. No significant
      differences were noted between the 3 groups regarding CR rate or survival. In
      total, 47 of 62 patients (75.8%) achieved CR. The median overall survival (OS)
      and median CR durations were 550 days and 341 days, respectively. Overall, the
      estimated survival rate at 20 years was 18.1%. The disease-free survival rate at
      20 years was 26.2%. According to univariate analysis, the most favorable
      pretreatment characteristic for achieving CR was age. A younger age (<40 years of
      age), platelet count >30 x 10(9)/L, having L1 morphology (French-American-British
      [FAB]classification subtype), female sex, and the absence of chromosomal
      abnormalities also helped improve survival rate. According to multivariate
      analysis, presence of Ph chromosome was found to be a major influencing factor
      for OS. Although higher doses of L-asp were administered than those used in
      previous studies, the adverse effect of L-asp was rarely identified. Therefore,
      it should be considered one of the key drugs for treatment of adult ALL. Further
      strategies still need to be developed to obtain better survival in adult ALL.

PMID- 11594518
TI  - Remission of acute myeloblastic leukemia after severe pneumonia treated with high
      dose methylprednisolone.
AB  - We report a case of acute myeloblastic leukemia (AML)-M2 (by French-American
      British classification) with t(8;21) (q22:q22) that was complicated with severe
      pneumonia. The patient tested positive by fluorescence in situ hybridization
      (FISH) for AML1 splitting and positive by reverse transcriptase polymerase chain
      reaction (RT-PCR) for chimeric AML1/MTG8 messenger RNA (mRNA), which indicated
      splitting of the MTG8 gene on chromosome 8 (q22) and the AMLI gene on chromosome
      22 (q22). High-dose methylprednisolone was administered, and the leukemic cells
      disappeared without chemotherapy, although dysplastic hematopoietic cells were
      observed transiently after the first therapy. After the disappearance of leukemic
      cells, FISH for AML1 splitting was negative, and real-time PCR results for
      quantitative chimeric AML1/ MTG8 mRNA were less than the detectable level,
      however, RT-PCR results for AML1/MTG8 mRNA remained positive. These findings
      suggest that the patient acquired morphological, cytogenetic. and possibly
      molecular genetic remission by the synergistic effects of severe infection and
      high-dose methylprednisolone.

PMID- 11594517
TI  - Intensification of chemotherapy using block therapies as consolidation and
      reinduction therapies for acute lymphoblastic leukemia during childhood.
AB  - Between April 1994 and March 1997, 143 children (age range, 1-15 years) with
      newly diagnosed acute lymphoblastic leukemia (ALL), except for those patients
      with t(9;22), were treated according to protocol-94 of the Osaka Childhood
      Leukemia Study Group. In this trial, the intensity of chemotherapy was enforced
      in the consolidation and reinduction phases by introducing AML-type block
      therapies consisting of concentrated administration of 4 to 6 drugs during 5 or 6
      days. For patients in the higher risk groups, rotational combination chemotherapy
      was introduced following the early phase. A total of 124 children with B-cell
      precursor ALL (B-pre ALL) were classified into 3 groups, the ultrahigh-risk group
      (UHRG) (15 patients), the high-risk group (HRG) (61 patients), or the standard
      risk group (SRG) (48 patients), based on age. leukocyte count, immunophenotype,
      central nervous system leukemia, response to treatment, and selected chromosomal
      abnormalities. The complete remission rate was 93%, and the 6-year event-free
      survival (EFS) rate was 79%+/-4%. EFS rates for the UHRG, HRG, and SRG groups
      were 67%+/-12%, 80%+/-6%, and 81%+/-6%, respectively. Nineteen patients with T
      cell ALL were treated with the protocol for the UHRG. Thirteen patients (68%)
      attained complete remission, and the 6-year EFS rate was 55%+/-12%. Thus,
      intensification of chemotherapy improved the EFS rate and AML-type block
      therapies appeared to be effective as the consolidation and reinduction therapies
      for B-pre ALL.

PMID- 11594519
TI  - Primary mediastinal large B-cell lymphoma: a comparative study with nodular
      sclerosis-type Hodgkin's disease.
AB  - The clinicopathological features of 10 patients with primary mediastinal large B
      cell lymphoma (PMLBCL) are described. The patients were aged 19 to 63 years, with
      a median age of 25.5 years. There were 5 men and 5 women. All patients presented
      with chest symptoms, and 6 presented with superior vena cava syndrome. Nine
      patients had bulky mediastinal tumors. The disease was confined within the thorax
      and contiguous lymph nodes, although multiple liver tumors were observed in 1
      patient. Laboratory findings included high lactate dehydrogenase levels and
      elevated C-reactive protein levels. The soluble interleukin 2-receptor level was
      high in 6 patients tested. A comparative study of PMLBCL and nodular sclerosis
      type Hodgkin's disease (NS-HD) with a mediastinal mass revealed substantial
      overlap in clinical features. Histopathological examination of biopsy specimens
      of PMLBCL revealed clusters of CD20+ large cells; however, CD30+ Hodgkin/Reed
      Sternberg-like cells were occasionally seen, raising the potential to misdiagnose
      PMLBCL as NS-HD. The patients with PMLBCL were treated with CHOP
      (cyclophosphamide, doxorubicin, vincristine, and prednisolone), biweekly CHOP, or
      MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone,
      and bleomycin) regimen, and 6 received consolidation radiotherapy to the involved
      field. With the exception of 1 patient who was primarily refractory to therapy, 9
      patients (90%) achieved complete response and 7 (70%) remain in continuous
      remission with a mean follow-up of 24 months.

PMID- 11594520
TI  - Pregnancy-associated cytotoxic lymphoma: a report of 4 cases.
AB  - The clinicopathological and biological significance of Hodgkin's disease and non
      Hodgkin's lymphoma, which are infrequently encountered in women of childbearing
      age, remains to be clarified. We recently reviewed 4 cases of non-Hodgkin's
      lymphoma of the T/natural killer (T/NK)-cell phenotype, all of which were
      associated with pregnancy and characterized by the expression of the cytotoxic
      granule-associated proteins T-cell intracellular antigen-1 and/or granzyme B. The
      4 cases selected had presented between November 1993 and May 1999. The criteria
      for selection were that the onset of clinical manifestations occurred during
      pregnancy or within 6 months after delivery. The patients comprised 1 patient
      with p80/anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma
      (ALCL), 1 with p80/ALK-negative ALCL, and 2 with peripheral T/NK-cell lymphomas
      of unspecified type. The diseases followed aggressive clinical courses: 3
      patients died within 6.5 months after diagnosis, and only 1 was still alive with
      the disease 17 months after diagnosis. The diseases appeared to progress rapidly
      after delivery. Maternal immunity and hormonal changes during pregnancy may be
      closely related to the biological behavior of these unusual tumors. This study
      is, to the best of our knowledge, the first to address pregnancy-associated
      cytotoxic lymphoma.

PMID- 11594521
TI  - Disparity between the macroglobulin-producing components of 2 cases of follicular
      lymphoma with Waldenstrom's macroglobulinemia.
AB  - We report 2 patients with follicular lymphoma (FL) which was accompanied by
      Waldenstrom's macroglobulinemia (WM). One patient was a 65-year-old woman and the
      other a 60-year-old man. Both patients showed a high level of circulating
      macroglobulin (4.6 g/dL and 3.6 g/dL, respectively) and bone marrow involvement
      of small lymphoid cells. Moreover, in each case, the macroglobulin-producing
      component and the follicular component were determined to be of the same clone
      based on their identical light-chain restriction pattern and other factors.
      However, there was a difference in the histopathological characteristics of the
      macroglobulin-producing components of the 2 patients, especially the cytoplasmic
      immunoglobulin (Ig)M+ cell distribution in the biopsied lymph nodes. Test results
      for the female patient showed intrafollicular proliferation of those cells. The
      male patient's test results showed that IgM+ cells were located in the narrow
      extrafollicular areas of the lymph nodes. Our observations suggest that at least
      2 different subtypes of FL may also be causative of a WM presentation.

PMID- 11594523
TI  - Posttreatment nadir M-protein level is a stronger discriminator of survival
      following plateau attainment than is percent reduction in M-protein in patients
      with IgG myeloma.
AB  - We conducted a retrospective study of patients with IgG or IgA myeloma who
      attained plateau to evaluate the relationships between survival and posttreatment
      nadir M-protein levels and between survival and the response to treatment
      evaluated by the percent reduction in M-protein. Of the 127 patients comprising
      92 IgG and 35 IgA myeloma patients with disease stages II or III, 51 (40.2%)
      attained plateau. For IgG myeloma patients who attained plateau, survival time
      was not affected by the percent reduction in M-protein (median survival, 59.5
      months for responding patients versus 54.4 months for nonresponding patients, P =
      .6910). Posttreatment nadir M-protein level, however, did affect survival time
      (median survival, 61.2 months for <3000 mg/dL versus 25.7 months for >3000 mg/dL,
      P = .0439). These findings suggest that the posttreatment nadir M-protein level
      is a stronger discriminator of survival following plateau attainment than the
      percent reduction of M-protein in patients with IgG myeloma.

PMID- 11594522
TI  - Superantigens and autoantigens may be involved in the pathogenesis of gastric
      mucosa-associated lymphoid tissue lymphoma.
AB  - To clarify the origin of tumor cells and the possible role of antigens in the
      pathogenesis of mucosa-associated lymphoid tissue lymphoma (MALTL) of the
      stomach, we analyzed the DNA sequences of the immunoglobulin (Ig) variable region
      gene from tumor cells of 4 patients with low-grade and 2 patients with high-grade
      MALTL associated with Helicobacter pylori infection. There were few somatic
      mutations in the Ig variable region gene, but intraclonal variations were
      observed in 2 of the 4 low-grade MALTL cases. In the remaining 2 low-grade MALTL
      and 1 of the 2 high-grade MALTL cases, somatic mutations and intraclonal
      variations were evident. In contrast, somatic mutations in the Ig variable region
      gene were prominent, but intraclonal variation was absent in the other high-grade
      MALTL cases. The deduced amino acid sequences of the antigen-binding fragments
      (Fab) from 2 MALTL cases revealed homology with anti-thyroglobulin antibodies, 3
      MALTL cases with lupus anti-DNA antibodies, and 1 MALTL case with a rheumatoid
      factor. Furthermore, the heavy-chain variable region 3 (V(H)3) family genes were
      used in 5 of the 6 MALTL cases and had conserved amino acid residues for binding
      to staphylococcal protein A (SpA), a superantigen of B cells. Considering that
      another superantigen, protein Fv, competes for binding to Fab with SpA and has
      been shown to play a major role in immune defenses against gut pathogens, SpA and
      possibly protein Fv may contribute to the development of MALTL. Thus, these
      observations suggest that most gastric MALTLs arise from memory B cells that are
      preliminarily activated by superantigens and autoantigens.

PMID- 11594524
TI  - A clinical analysis of 52 adult patients with hemophagocytic syndrome: the
      prognostic significance of the underlying diseases.
AB  - We retrospectively analyzed 52 adult patients with hemophagocytic syndrome (HPS).
      The underlying diseases were heterogeneous, including malignant lymphoma
      (lymphoma-associated hemophagocytic syndrome [LAHS]) in 26 patients, systemic
      lupus erythematosus in 3 patients, viral infections in 7 patients, and bacteria]
      or fungal infections in 6 patients. More than 83% of patients received
      prednisolone as an initial treatment. Multiple-agent chemotherapies
      (cyclophosphamide, doxorubicin, and vincristine) were administered to 96% of LAHS
      patients after a histopathological diagnosis of lymphoma. HPSs were controllable
      and remissions were achieved except for those patients with LAHS, fulminant
      Epstein-Barr virus-associated HPS, and an immunosuppressive state. Twenty-one
      (81%) of the LAHS patients had uncontrollable HPS and died of multiple organ
      failure and disseminated intravascular coagulation. The median survival time of
      LAHS patients was 83 days. In contrast, 3 (12%) of the other HPS patients died of
      multiple organ failure within 44 days.The clinical manifestations and the
      laboratory findings of LAHS and the other HPSs were too variable to establish the
      prognosis based only on the findings at the onset of HPS. The prognostic factors
      of adult HPS were found to be the underlying diseases, notably malignant lymphoma
      and infections, accompanied by the immunosuppressive state.

PMID- 11594525
TI  - CD34+-selected autologous peripheral blood stem cell transplantation conditioned
      with total body irradiation for malignant lymphoma: increased risk of infectious
      complications.
AB  - Although high-dose chemotherapy with autologous peripheral blood stem cell
      transplantation (autoPBSCT) has been shown or confirmed to be an effective
      treatment for high-risk and relapsed non-Hodgkin's lymphoma (NHL), relapse after
      autoPBSCT remains a serious problem. In a clinical trial to overcome relapse, we
      adopted a treatment plan in which PBSCs purified in vitro to CD34+ cells to
      deplete tumor cells (CD34+ autoPBSCT), total body irradiation (TBI) of 1200 cGy,
      and melphalan, 180 mg/m2, were used as a preconditioning regimen. Eighteen
      patients with relapsed or high-risk NHL participated in the study. This study
      compared the incidence of complications following CD34+ autoPBSCT preconditioned
      with the TBI regimen (n = 10): the TBI group; CD34+ autoPBSCT with the non-TBI
      regimen (n = 8): the non-TBI group; and unselected autoPBSCT with the non-TBI
      regimen (n = 19): the unselected autoPBSCT control group. After day 30
      posttransplantation, 6 of 10 patients treated with the TBI regimen developed 11
      infectious complications in total, compared with only 1 of 8 patients treated
      with the non-TBI regimen and 4 of 19 patients given unselected autoPBSCT. Two
      fatal complications occurred in the TBI group, but none occurred in the other 2
      groups. The CD4+ lymphocyte count at 1 month posttransplantation was
      significantly lower in the TBI group than in the unselected autoPBSCT group.
      These findings suggest that the addition of TBI to the preconditioning regimen
      for CD34+ autoPBSCT is associated with an increased incidence of severe
      infectious complications after transplantation.

PMID- 11594526
TI  - Acquired storage-pool disorders occurring late after allogeneic bone marrow
      transplantation: partial activation of platelets in asymptomatic patients.
AB  - Bone marrow transplantation (BMT) may be complicated by coagulation
      abnormalities. The present study evaluated whether platelets might be activated
      in patients who had undergone BMT without significant coagulopathy. The patients
      selected had received allogeneic BMTs a median of 39 months before the study
      (range, 11-124 months) and had not received cyclosporine, FK506 (tacrolimus), or
      other medication affecting cyclo-oxygenase for at least 3 months prior to the
      collection of blood samples. Furthermore, patients had platelet counts greater
      than 100 x 10(9) cells/L and normal serum creatinine levels. Twenty-five healthy
      volunteers acted as controls. Platelet aggregation studies and a mepacrine assay
      of platelets showed abnormal aggregation and decreased staining in some patients.
      The platelet storage-pool adenosine 5'-triphosphate (ATP) level in 15 patients
      after BMT was 0.45+/-0.24 micromol per 10(11) platelets, whereas the level in 18
      controls was 1.03+/-0.36 micromol per 10(11) platelets (P = .00078). The total
      ATP levels of platelets in patients and controls were 4.33+/-1.14 and 5.63+/-1.51
      micromol per 10(11) platelets, respectively (P = .016). With the exception of 1
      patient, plasma levels of thrombomodulin and von Willebrand factor were all
      within the normal range. The average plasma level of 11-dehydrothromboxane B2 was
      significantly increased in 15 patients after BMT compared with controls, 20.6+/
      8.2 and 10.3+/-1.2 pg/mL, respectively (P = .0004). These findings suggest a long
      term process of platelet activation in patients after BMT and, following the
      cessation of cyclosporine, development of acquired storage-pool disorder of
      platelets.

PMID- 11594527
TI  - Severe autoimmune thrombocytopenia after allogeneic bone marrow transplantation
      for aplastic anemia.
AB  - Autoimmune thrombocytopenia (AITP) after bone marrow transplantation (BMT) was
      suggested to occur by immune dysregulation mainly in association with graft
      versus-host disease (GVHD). Here we present a patient who developed severe AITP
      after BMT. A 40-year-old woman with severe aplastic anemia received a BMT from a
      partially HLA-matched brother. Despite myeloid and erythroid engraftments,
      platelet recovery was delayed. All bone marrow cells were 46,XY and were derived
      from the donor. Grade I acute GVHD involving skin developed from day 34
      posttransplantation, but promptly responded to prednisolone in addition to a
      prophylactic dose of tacrolimus. With the tapering of prednisolone,
      thrombocytopenia progressed without substantial changes in the white blood cell
      count, hemoglobin concentration, or reticulocyte count. On day 188, the patient
      developed chronic GVHD involving skin and liver, which promptly responded to the
      readministration of prednisolone and increased tacrolimus. However, the patient's
      platelet count decreased to 9 x 10(9) cells/L on day 222. The platelet-associated
      immunoglobulin G (PAIgG) values were elevated. Bone marrow examination showed
      hypercellularity with plentiful megakaryocytes. The number of colony-forming
      units-megakaryocyte was within the normal range. The elevated PAIgG values and a
      correlation between thrombocytopenia and the intensity of the immunosuppressive
      agents strongly suggested a causative role of the autoimmune mechanisms for
      thrombocytopenia in this patient.

PMID- 11594528
TI  - A case of Evans' syndrome complicated with multiple nocardial abscesses: a long
      term survivor under corticosteroid therapy.

PMID- 11594529
TI  - Host origin of marrow mesenchymal stem cells following allogeneic cord-blood stem
      cell transplantation.

PMID- 11594531
TI  - Embryo effects in human implantation: embryonic regulation of endometrial
      molecules in human implantation.
AB  - Embryonic implantation requires coordinated development of the blastocyst and the
      maternal endometrium. Considerable advances have been made in the understanding
      of the cell biology of human embryo and maternal endometrium as separate
      entities. Nevertheless, communication between them and their reciprocal effects
      on each other constitute an exciting and as-yet unsolved problem in reproductive
      medicine. Cross-talk among the embryo, endometrium, and the corpus luteum are
      known to occur in ruminants and primates; more specifically, endometrial
      embryonic interactions have been reported in rodents and primates. Here, we
      present updated information in humans on the embryonic regulation of endometrial
      epithelial molecules such as chemokines, adhesion molecules, antiadhesion
      molecules, and leptin during the apposition and adhesion phases of human
      implantation. Also the embryonic induction of apoptosis in endometrial epithelial
      cells as a mechanism for crossing the epithelial barrier will be described.

PMID- 11594530
TI  - Remission of idiopathic thrombocytopenic purpura by eradicating Helicobacter
      pylori after omeprazole monotherapy.

PMID- 11594532
TI  - Endocrine and paracrine regulation of endometrial angiogenesis.
AB  - The human endometrium is a complex tissue comprised of different cell types,
      including epithelial, stromal, inflammatory, perivascular, and blood vessel
      cells. The hormonal receptivity and distribution of these cell populations change
      during the menstrual cycle. Cyclical endometrial growth is dependent on its
      ability to regenerate a vascular capillary network, which grows in parallel with
      the proliferation and differentiation of the endometrial lining. Natural hormonal
      effects on the endometrium and endocrine manipulation of this tissue, in response
      to the use of exogenous steroid therapies, can affect endometrial capillary
      proliferation and function, leading to clinical abnormalities of uterine
      bleeding. We propose that the regulation of endometrial angiogenesis is mediated
      indirectly via complex interactions among cell types. Our laboratory has focused
      on a prototypical member of the angiogenic proteins, vascular endothelial growth
      factor (VEGF)-A. In this paper we present data demonstrating that VEGF-A
      expression in normal endometrial epithelial and stromal cells and in Ishikawa
      adenocarcinoma cells is increased by an ovarian steroid, estradiol. Infiltrating
      immune cells, particularly polymorphonuclear granulocytes, also are sources of
      VEGF-A. In inflammatory conditions involving the endometrium (e.g.,
      endometriosis), a proinflammatory cytokine, IL-1beta, can mediate neoangiogenesis
      by inducing VEGF-A gene transcription. Thus, endometrial vascularization is
      effected by both endocrine and paracrine pathways.

PMID- 11594533
TI  - Endometrial quality in infertile women with endometriosis.
AB  - Several analyses in our infertility (IVF) and oocyte donation programs were
      carried out to gain clinical knowledge of the factors involved in the etiology of
      endometriosis-associated infertility. We first compared the IVF outcomes in women
      with tubal infertility and endometriosis. The results indicated that patients
      with endometriosis had a poorer IVF outcome in terms of reduced pregnancy rate
      per cycle, per transfer, and reduced implantation rate per embryo replaced. We
      then evaluated embryo development in vitro in women with and without
      endometriosis who underwent IVF and embryo replacement 72 hours after oocyte
      retrieval. We observed that compared to controls, patients with endometriosis had
      a significantly reduced number of blastomeres per embryo as well as an increased
      incidence of arrested embryos in vitro. In subsequent studies we compared
      fertility parameters in patients receiving donor oocytes. We noted that when
      donor oocytes came from patients without known endometriosis, embryo development
      and implantation rates were similar in patients with and without endometriosis.
      However, when the results of oocyte donation were classified according to the
      nature of the oocytes donated, patients who received embryos derived from oocytes
      from women with endometriotic ovaries showed a significantly reduced implantation
      rate compared to the controls. Taken together, these observations suggest that
      IVF in patients with endometriosis may be related to alterations within the
      oocyte, which, in turn, result in embryos of lower quality with a reduced ability
      to implant.

PMID- 11594534
TI  - Endometrial anomalies in women with endometriosis.
AB  - Endometriotic lesions are defined by extrauterine growth of endometrial glands
      and stroma. Retrograde menstruation with subsequent attachment, invasion, and
      neovascularization are believed to give rise to the endometriotic lesions. As
      most women exhibit some degree of retrograde menstruation, some other
      unidentified factor(s) must render certain women susceptible to attachment and
      growth of ectopic endometrial tissue. A variety of theories have been proposed to
      account for this susceptibility, including genetic predisposition, aberrant
      immunological response, and an altered peritoneal environment. Ectopic
      endometriotic lesions are histologically similar to their putative eutopic
      precursors, yet significant biochemical differences exist between these two
      tissues. Less information is available regarding differences between eutopic
      endometrium from women with or without endometriosis. This report describes
      anomalies in structure, proliferation, immune components, adhesion molecules,
      proteolytic enzymes and inhibitors, steroid and cytokine production and
      responsiveness, and gene expression and protein production that have been
      identified in eutopic endometrium from women with endometriosis.

PMID- 11594535
TI  - The mechanisms of placental viral infection.
AB  - The placenta is a dynamic organ whose structure and function change throughout
      pregnancy. There is compelling evidence that the placenta plays an integral role
      in the vertical transmission of viruses, such as cytomegalovirus and human
      immunodeficiency virus, from the mother to the fetus. Although the sequelae of
      congenital viral infection (i.e., fetal anomalies, intrauterine fetal death, and
      persistent postnatal infection) may be devastating, very little is known about
      the passage of viruses across the placenta and the pathologic consequences of
      placental viral infection. We postulate that the syncytiotrophoblast, which forms
      a continuous barrier between the maternal and fetal circulation, is relatively
      resistant to viral infection. In support of this hypothesis, we observed that the
      susceptibility of trophoblast cells to infection by adenovirus and herpes simplex
      virus and the expression of viral receptors were reduced as trophoblast cells
      terminally differentiated into syncytiotrophoblast. Conversely, we observed that
      undifferentiated, extravillous trophoblast cells, which are susceptible to
      adenovirus infection, underwent pathologic changes (i.e., apoptosis) when
      infected by adenovirus in the presence of decidual lymphocytes (which were used
      to simulate the maternal immune response to viral infection). Based on these
      findings, we speculate that viral infection of extravillous trophoblast cells may
      negatively impact the process of placental invasion and predispose the mother and
      fetus to adverse reproductive outcomes that result from placental dysfunction.

PMID- 11594536
TI  - Biochemistry and molecular biology of trophoblast invasion.
AB  - Cytotrophoblastic cells (CTBs) from first-trimester placenta form columns of
      invasive CTBs. This invasive behavior is due to the ability of CTBs to secrete
      matrix metalloproteinases (MMPs), since tissue inhibitor of MMPs (TIMP) inhibits
      their invasiveness in the extracellular space. Although CTBs behave like metastic
      cells, in vivo they are only transiently invasive (first trimester), and their
      invasion is normally limited only to the endometrium and to the proximal third of
      the myometrium. This temporal and spatial regulation of trophoblast invasion is
      believed to be mediated in an autocrine way by trophoblastic factors and in a
      paracrine way by uterine factors. Several types of regulators have been
      investigated: hormones, extracellular matrix glycoproteins, and cytokines or
      growth factors. This review is not intended to be an exhaustive catalogue of
      potential regulators of trophoblast invasion but is aimed at summarizing the most
      important categories of factors affecting trophoblast-endometrium interactions.

PMID- 11594537
TI  - Uterine contractility: vaginal administration of the beta-adrenergic agonist,
      terbutaline. Evidence of direct vagina-to-uterus transport.
AB  - Spontaneous uterine contractility during the menstrual cycle is required for
      menstruation, gamete transport, and, most likely, embryo nidation. Abnormal
      uterine contractility has been linked to dysmenorrhea, a condition associated
      with painful uterine cramping. Based on previous studies with progesterone, we
      have postulated the existence of a portal system that is responsible for some
      degree of direct vagina-to-uterus transport of administered compounds (i.e., the
      "first uterine pass effect"). It is possible that treatment with uterorelaxing
      substances, particularly beta-adrenergic agonists, may alleviate the uterine
      discomfort that accompanies dysmenorrhea. However, side effects encountered with
      oral administration of beta-agonists limit their utility. Alternatively, vaginal
      delivery of beta-agonists could solve this dilemma by enhancing their efficacy
      and reducing side effects. Therefore, in the current study we used hysterectomy
      specimens and an in vitro uterine perfusion system to test the vagina-to-uterus
      transport of [3H]terbutaline, a well-known beta-agonist. With the use of
      autoradiographic and scintillation counting techniques, our results clearly show
      progressive diffusion of labeled terbutaline from the rim of vaginal tissue
      through the uterus during the first 12 hours of perfusion. This indicates that
      uterine targeting of terbutaline can be accomplished through vaginal
      administration, suggesting a new therapeutic modality in women's health care.

PMID- 11594538
TI  - Maternal-embryonic cross-talk.
AB  - The human menstrual cycle evolved to prepare the uterus for blastocyst
      implantation, which is fundamentally under the control of gonadal steroids.
      Ovarian hormones induce marked morphological, physiological, and biochemical
      changes within reproductive tissues. These changes in turn induce alterations in
      the biosynthetic activity and release of a myriad of locally produced proteins
      into the microenvironment of the reproductive tract. These same factors may be
      further modified by proteins secreted by the developing embryo and accompanying
      cumulus cells in intimate contact with reproductive epithelium in a network
      signaling process. Communication is not one-way, but rather maternal-embryonic
      cross-talk may occur as maternal proteins are secreted into the microenvironment
      of the oviduct and uterus, facilitating fertilization and early embryo
      development and serving as homing beacons for blastocyst nidation. The
      communicating language facilitating this dialogue includes cytokines, growth
      factors, angiogenic factors, apoptotic factors, adhesion molecules, and,
      potentially, homeotic genes.

PMID- 11594539
TI  - Contractility of the nonpregnant uterus: the follicular phase.
AB  - Recent renewed interest in uterine contractility stems from the possibility of
      directly visualizing uterine contractility on images generated by high-resolution
      ultrasound probes. During the menstrual cycle, three typical patterns of uterine
      contractility have been recognized. During the luteofollicular transition and
      early follicular phase (menses), the contractile event involves all layers of the
      myometrium and exerts antegrade (from fundus to cervix) expulsive forces.
      Characteristically, uterine contractions are often perceived by women at the time
      of menses, sometimes reaching the level of painful cramps (dysmenorrhea). In the
      late follicular phase, uterine contractility involves only the subendometrial
      layers of the myometrium and is never perceived by women. The primary function of
      uterine contractility in the late follicular phase is to facilitate the
      retrograde (cervix to fundus) transport of sperm towards the distal end of the
      fallopian tubes where fertilization normally takes place. Finally, the uterus
      reaches a stage of quiescence after ovulation (under the influence of
      progesterone) that characterizes the major part of the luteal phase. The present
      review summarizes our understanding of the physiological role of uterine
      contractility during the follicular phase and the possible implications in
      pathological circumstances such as endometriosis and dysmenorrhea.

PMID- 11594540
TI  - Assessing uterine receptivity in 2001: ultrasonographic glances at the new
      millennium.
AB  - The understanding and control of embryo implantation represents the major
      challenge for assisted reproductive technologies. Along with developments in
      basic research and efforts to optimize embryo quality, the improvement of
      noninvasive and reliable methods to assess uterine receptivity constitutes an
      important step toward meeting such a challenge. Today, ultrasound-based
      approaches to evaluate endometrial echogenicity and uterine perfusion and
      contractility are available for practical use. Increasing evidence indicates that
      echogenic patterns of the endometrium reflect histologic processes that are
      involved in the establishment of receptivity. This constitutes a possible
      explanation for the reported association between premature hyperechogenic
      patterns of the endometrium and poor implantation rates. Nevertheless, additional
      studies aiming at correlating further morpho-biochemical events in the
      endometrium with its echogenicity patterns are needed. Further, developments in
      vascular assessment by Doppler, Doppler-related, and vascular detection
      technologies will also be instrumental in monitoring and improving vascular
      changes that lead to uterine receptivity. Finally, data supporting the hypothesis
      that uterine contractility, as visualized by ultrasound, influences in vitro
      fertilization-embryo transfer (IVF-ET) pregnancy rates encourage further
      investigation on both the regulation and control of uterine contractions. This
      article discusses some of the advantages and limitations of ultrasonographic
      assessments of uterine receptivity in the perspective of the new millennium.

PMID- 11594541
TI  - Methods and devices for the management of term and preterm labor.
AB  - In this review, we outline studies showing that the uterus (myometrium) and
      cervix pass through a conditioning step in preparation for labor. This step is
      not easily identifiable with present methods designed to assess the uterus or
      cervix. In the uterus, this seemingly irreversible step consists of changes in
      the electrical properties that make muscle more excitable and responsive and
      produce forceful contractions. In the cervix, the step consists of softening of
      the connective tissue components. Progesterone and nitric oxide appear to have
      important roles in these processes. The progress of labor can be assessed
      noninvasively using electromyographic (EMG) signals from the uterus (the driving
      force for contractility) recorded from the abdominal surface. Uterine EMG bursts
      detected in this manner characterize uterine contractile events during human and
      animal pregnancy. A low uterine EMG activity, measured transabdominally
      throughout most of pregnancy, rises dramatically during labor. EMG activity also
      increases substantially during preterm labor in humans and rats and may be
      predictive of preterm labor. A quantitative method for assessing the cervix is
      also described. A collascope estimates cervical collagen content from a
      fluorescent signal generated when collagen crosslinks are illuminated with an
      excitation light of about 340 nm. The system has proved useful in rats and humans
      at various stages of pregnancy and indicates that cervical softening occurs
      progressively in the last one-third of pregnancy. In rats, collascope readings
      correlate with resistance measurements made in the isolated cervix, which may
      help to assess cervical function during pregnancy and indicate controls and
      treatments.

PMID- 11594542
TI  - Understanding preterm labor.
AB  - Increased uterine contractility at term and preterm results from activation and
      then stimulation of the myometrium. Activation can be provoked by mechanical
      stretch of the uterus and by an endocrine pathway resulting from increased
      activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis. In fetal sheep,
      increased cortisol output during pregnancy regulates prostaglandin H synthase
      type 2 (PGHS2) expression in the placenta in an estrogen-independent manner,
      resulting in increased levels of PGE2 in the fetal circulation. Later increases
      in maternal uterine expresssion of PGHS2 require elevations of estrogen and lead
      to increased concentrations of PGF2alpha in the maternal circulation. Thus,
      regulation of PGHS2 at term is differentially controlled in fetal (trophoblast)
      and maternal (uterine epithelium) tissue. This difference may reflect expression
      of the glucocorticoid receptor (GR), but not estrogen receptor (ER), in placental
      trophoblast cells. In women, cortisol also contributes to increased PG production
      in fetal tissues through upregulation of PGHS2 (amnion and chorion) and
      downregulation of 15-OH PG dehydrogenase (chorion trophoblasts). The effect of
      cortisol on chorion expression of PGDH reverses a tonic stimulatory effect of
      progesterone, potentially through a paracrine or autocrine action. We have
      interpreted this interaction as a reflection of "progesterone withdrawal" in the
      primate, in relation to birth. Other agents, such as proinflammatory cytokines,
      similarly upregulate PGHS2 and decrease expression of PGDH, indicating the
      presence of several mechanisms by which labor at term or preterm may be
      initiated. These different mechanisms need to be considered in the development of
      strategies for the detection and management of the patient in preterm labor.

PMID- 11594543
TI  - Ectopic pregnancy from surgical emergency to medical management.
AB  - During the past 25 years, the incidence of ectopic pregnancy has progressively
      increased while the morbidity and mortality have substantially decreased, and the
      treatment has progressed from salpingectomy by laparotomy to conservative surgery
      by laparoscopy and more recently to medical therapy. This therapeutic transition
      from surgical emergency to medical management has been attributed to early
      diagnosis through the use of sensitive assays for hCG and the high definition of
      vaginal ultrasound. By using these sensitive diagnostic tools, we are now able to
      select those patients who are most likely to respond to medical management versus
      those who are at high risk of rupture and require surgery. Besides being less
      invasive and associated with significantly lower risks, medical therapy with
      methotrexate results in significant cost savings, which have been calculated to
      be approximately $3,000 per treated patient. Our goal is to identify those
      patients with ectopic pregnancy who are most likely to respond to methotrexate
      therapy and least likely to develop significant side effects. Recent studies have
      helped us define the predictors of success with methotrexate treatment in women
      with ectopic pregnancy. The reported success rates of treating ectopic pregnancy
      with methotrexate vary from 71% to 100%. The highest success rates have been
      reported from institutions that have detailed diagnostic and therapeutic
      protocols, readily available assays for serum hCG levels, high-resolution vaginal
      probe ultrasound, and support staff that can closely monitor clinical response.
      The importance of developing specific protocols to create a clinical environment
      that supports the effective use of medical therapy for ectopic pregnancy is
      confirmed by the associated cost savings, decreased morbidity, and patient
      preference. Modern diagnostic advances and minimally invasive treatments coupled
      with improved success rates for assisted reproductive technologies should reduce
      the morbidity and mortality associated with ectopic pregnancy and offer the
      affected couple a much more optimistic outlook for subsequent reproductive
      potential.

PMID- 11594544
TI  - Laparoscopic management of adnexal masses the opportunities and the risks.
AB  - Suspected ovarian neoplasm is a common clinical problem affecting women of all
      ages. Although the majority of adnexal masses are benign, the primary goal of
      diagnostic evaluation is the exclusion of malignancy. It has been estimated that
      approximately 5-10% of women in the United States will undergo a surgical
      procedure for a suspected ovarian neoplasm during their lifetime. Despite the
      magnitude of the problem, there is still considerable disagreement regarding the
      optimal surgical management of these lesions. Traditional management has relied
      on laparotomy to avoid undertreatment of a potentially malignant process.
      Advances in detection, diagnosis, and minimally invasive surgical techniques make
      it necessary now to review this practice in an effort to avoid unnecessary
      morbidity among patients. Here, we review the literature on the laparosopic
      approach to the treatment of the adnexal mass without sacrificing the principles
      of oncologic surgery. We highlight potentials of minimally invasive surgery and
      address the risks associated with the laparoscopic approach.

PMID- 11594545
TI  - Fertility and maternal age strategies to improve pregnancy outcome.
AB  - In humans, the live birth rate drops precipitously with increasing maternal age,
      and this decline is associated with increases in the incidence of oocyte and
      embryo aneuploidy. Preimplantation aneuploidy screening has improved pregnancy
      outcome by significantly lowering the miscarriage rate. Nevertheless, aneuploidy
      screening only identifies the affected embryos; it does not attempt to correct
      the underlying biologic problem. Anomalies in chromosome segregation can result
      from a dysfunctional first or second meiotic division in the egg or develop after
      fertilization during the first few mitoses of early embryonic development. In
      both instances, ooplasmic anomalies may account for the nuclear problem. Low cell
      levels of cytoplasmic proteins (e.g., cytoskeletal elements, enzymes, energy
      stores, cell cycle regulatory proteins) may lead to a dysfunctional division of
      chromosomes during egg maturation or following fertilization. Ooplasmic injection
      is a micromanipulation technique that has produced pregnancies in patients with a
      history of poor-quality, fragmented embryos. Germinal vesicle transfer is a
      research procedure used to investigate the ooplasmic-nuclear interplay regulating
      cell cycle, maturation, and fertilization. Both these techniques may prove to be
      effective in improving the quality of eggs from patients of advanced maternal
      age.

PMID- 11594546
TI  - Laparoscopic myomectomy fertility results.
AB  - The appearance of uterine myomas has been linked to infertility. It has been
      suggested that surgical management of myomas by laparoscopic myomectomy improves
      fertility rates in these group of patients. In this paper we initially describe
      specific aspects of the surgical technique of laparoscopic myomectomy including
      the set-up, precise technique for hysteroromy, enucleation of the myoma, suturing
      of the uterus, and extraction of the myoma. We detail recent findings that
      demonstrate improved fertility rates in women undergoing laparoscopic myomectomy.
      We recommend that, when criteria for selection of patients is strictly adhered to
      and patients present with no other associated infertility, laparoscopic
      myomectomy be used to increase the implantation rate.

PMID- 11594547
TI  - Management of deep endometriosis.
AB  - Deep endometriosis is defined as an endometriotic lesion that penetrates the
      retroperitoneal space for a distance of > or =5 mm. Deep endometriosis is
      extremely active, occurs in phase with eutopic endometrium, evolves progressively
      with age, and is most often located in the pouch of Douglas, the rectovaginal
      septum, the uterosacral ligaments, and occasionally in the uterovesical fold.
      These lesions are associated with pelvic pain, the intensity of which is
      proportional to the depth of penetration. It is clear that choice of treatment
      depends on the location of the endometriotic lesion. In this paper we describe
      our methods for the initial diagnosis and subsequent treatment of deep
      endometriosis. These include consultation and clinical examination protocols, use
      of rectal endoscopic ultrasonography (EUS), magnetic resonance imaging (MRI), and
      transvaginal ultrasonography techniques in diagnosis and surgical treatment
      approaches.

PMID- 11594548
TI  - Cancer and pregnancy.
AB  - Carcinoma of the cervix is the most frequently diagnosed cancer in pregnancy.
      Still, it is an unusual situation. An abnormal Pap smear during pregnancy is a
      much more common occurrence and fortunately one that can be managed
      conservatively. Although definitive treatment for intraepithelial disease can be
      delayed until the postpartum period, diagnostic evaluation should be done when
      the abnormal Pap smear is present. Invasive cancer management is dependent on
      gestational age of the fetus. Pregnancy affords an excellent opportunity to
      screen for cervical neoplasia.

PMID- 11594549
TI  - Uterine transplantation, abdominal trachelectomy, and other reproductive options
      for cancer patients.
AB  - More and more women with cancer issues are now raising fertility concerns as
      survival improves and childbearing is delayed. Pregnancy is no longer
      contraindicated in cancer patients including breast and endometrial cancer
      survivors. In fact, survival in patients treated for breast cancer who
      subsequently become pregnant is actually higher than that in patients who do not
      become pregnant. "Therapeutic" abortions are no longer recommended. Assisted
      reproductive technology (ART) have been associated with ovarian neoplasms, but
      the association is probably not causal. Neither ART nor hormone replacement is
      contraindicated in cancer patients. Our institution is very supportive of
      patients and the difficult decisions cancer survivors face. Using a program of
      counseling and close collaboration between oncologists, perinatologists, and
      reproductive endocrinologists, informed patients are offered every possible
      option, including ART and uterine transplantation, to achieve their family
      planning objectives.

PMID- 11594550
TI  - Role of exogenous and endogenous hormones in endometrial cancer: review of the
      evidence and research perspectives.
AB  - Endometrial carcinoma is the most common cancer of the female reproductive organs
      in the United States. International comparisons reveal that the incidence of
      endometrial cancer vary widely between different countries with the highest rates
      observed in North America and Northern Europe, intermediate rates in Eastern
      Europe and Latin America, and lowest rates in Asia and Africa. International
      variation in endometrial cancer rates may represent differences in the
      distribution of known risk factors, which include obesity, postmenopausal
      estrogen replacement, ovarian dysfunction, diabetes mellitus, infertility,
      nulliparity, and tamoxifen use. Most of the risk factors for endometrial cancer
      can be explained within the framework of the unopposed estrogen hypothesis, which
      proposes that exposure to estrogens unopposed by progesterone or synthetic
      progestins leads to increased mitotic activity of endometrial cells, increased
      number of DNA replication errors, and somatic mutations resulting in malignant
      phenotype. Although the impact of exogenous hormone replacement was intensively
      studied during the last two decades, less is known about the effects of
      endogenous hormones in endometrial cancer. A review of available experimental,
      clinical, and epidemiologic data suggests that in addition to estrogens, other
      endogenous hormones, including progesterone, androgens, gonadotropins, prolactin,
      insulin, and insulin-like growth factors, may play a role in the pathogenesis of
      different histopathologic types of endometrial cancer.

PMID- 11594551
TI  - Doppler investigation in intrauterine growth restriction--from qualitative
      indices to flow measurements: a review of the experience of a collaborative
      group.
AB  - In 1997 we started a collaboration among three groups, combining our experience
      with Doppler examination of the human fetus, blood flow studies on fetal lamb,
      and mathematical modeling of human circulation. In preliminary investigations on
      fetal lambs, the same Doppler method designed for the human fetus was used to
      measure venous blood flow in the umbilical veins of seven fetal lambs. Doppler
      measurements and diffusion technique groups for umbilical venous flow were
      210.8+/-18.8 and 205.7+/-38.5 ml/min/kg, respectively (p = 0.881). In human
      pregnancy the interobserver variabilities for the vein diameter, mean velocity,
      and absolute umbilical venous blood were 2.9%, 7.9%, and 12.7%, respectively. A
      cross-sectional study allowed us to establish normal reference values. Venous
      blood flow/kg of estimated fetal weight showed a nonsignificant linear reduction
      with gestational age, from 128.7 ml/min/kg at 20 weeks to 104.2 ml/min/kg at 38
      weeks. In a series of 37 growth-restricted fetuses, the UV flow per kilogram was
      significantly lower in the more severe growth-restricted fetuses (abdominal
      circumference below the second percentile and abnormal umbilical arterial p.i.)
      than in normal comparable fetuses (p < 0.001). In a series of 140 normal fetuses,
      we calculated that the absolute blood flow rate in the ductus venosus (DV)
      increases significantly with advancing gestational age from 20 to 38 weeks of
      gestation (from 23.2+/-9.6 ml/min to 43.5+/-21.5 ml/min). This means that the
      percentage of umbilical blood flow shunted through the DV decreases significantly
      during gestation (from 50% at midgestation to 20% at 38 weeks). In a series of 45
      growthrestricted fetuses, delivered because of nonreactive fetal heart rate
      (group 2) and for other reasons but still with a normal heart rate pattern (group
      1), we measured the ductal inlet diameter. In these fetuses, the diameters at the
      ductal isthmus, normalized for the dimension of the abdominal circumference
      (inlet diameter/abdominal circumference), were significantly larger (group 1 =
      6.8+/-2.3; group 29.4+/-2.8 ) than in the control group (6.1+/-0.3). This means
      that in this subset of fetuses the amount of blood shunted can be increased as a
      compensatory mechanism.

PMID- 11594552
TI  - A critical birth weight and other determinants of survival for infants with
      severe intrauterine growth restriction.
AB  - Our objective was to assess the perinatal management and neonatal outcomes of
      premature, severely intrauterine growth-restricted (IUGR) neonates. A cohort of
      neonates <1000 grams, < or = first percentile for weight, and <37 weeks'
      gestation was identified and matched 2:1 to two control sets of premature,
      appropriate-for-gestational age (AGA) infants-one with similar gestational age
      (AGA-GA group) and the other with similar birth weight (AGA-BW group) to
      determine the effect of IUGR on the outcome of the premature infant. The IUGR
      group was then examined in detail for descriptive statistics. Data were analyzed
      by t-tests and Chi-square analyses where appropriate. The IUGR infants had worse
      outcomes than AGA-GA controls but had somewhat better results than the AGA-BW
      controls. In the IUGR group, a birth weight less than 550 grams was significantly
      associated with neonatal death (p < 0.001). However, increasing gestational age
      was not associated with neonatal survival (p = 0.661) if birthweight remained
      below 550 grams. Classical cesarean delivery was associated with neonatal death
      (p = 0.003). Neonatal variables associated with poor outcome included patent
      ductus arteriosus (p = 0.034), feeding intolerance (p = 0.046), and failure to
      thrive (p = 0.05). Overall, neonatal survival was 73%. Of the surviving neonates,
      69% had evidence of neurodevelopmental delay when tested at 6 and 12 months.
      Premature, growth-restricted neonates with birth weights of <550 grams versus
      those of >550 grams have dismal outcomes despite a gestational age that is
      compatible with survival.

PMID- 11594553
TI  - Inhibin, activin, and follistatin in human fetal pituitary and gonadal
      physiology.
AB  - BACKGROUND: Activin has been previously demonstrated to directly stimulate the
      synthesis of gonadotropin-releasing hormone (GnRH) receptors and to increase
      follicle-stimulating hormone (FSH) secretion in nonhuman pituitary cell cultures
      (PCCs). Currently, knowledge of the physiological role of these peptides in
      primates is still far from complete. Moreover, several results in macaque monkeys
      failed to support an unequivocal role for inhibin in FSH suppression. Whereas the
      bioactivity of inhibin and activin has been demonstrated in rat PCCs, no data
      exist on human pituitary response to these peptides either in vivo or in vitro.
      METHODS: We studied the secretion of FSH and luteinizing hormone (LH) by
      dispersed human fetal pituitary cells from midtrimester abortions in response to
      recombinant human (rh-) activin-A, inhibin-A, and other secretagogues. After
      mechanical and enzymatic dispersion, the human fetal pituitary cells were
      cultured on an extracellular matrixlike-material-coated 24-well plate. After 3
      days' incubation in serum-containing medium, the PCCs were washed and
      preincubated for 90 min in serum-free medium and incubated with activin-A,
      inhibin-A, TGF-beta, follistatin, sex steroids, and GnRH, in quadruplicate.
      RESULTS: Activin-A was a potent secretagogue for FSH secretion. GnRH (20 ng/ml)
      was more potent than rh-activin-A for LH secretion. Nevertheless, a significant
      increase in LH secretion into the medium was brought about by rh-activin-A.
      Inhibin decreased FSH and LH secretion, but the LH response to inhibin was less
      prominent than that of FSH. GnRH opposed the inhibitory effect of inhibin on LH
      secretion. In dynamic, short-term, repetitive exposure of fetal pituitary
      fragments to rh-activin-A (superfusion), we could not receive a similar increase
      in LH and FSH as in static incubations, as opposed to a short GnRH exposure. In
      addition to their endocrine, paracrine, and autocrine effects, and in addition to
      their role as possible markers, the TGF-beta superfamily members may affect
      embryogenesis and possibly immunomodulation of the embryo and fetus. The role of
      activin and inhibin as intragonadal regulators is hypothesized. The pro-alphaC
      inhibin precursor may act as an FSH receptor antagonist. CONCLUSIONS: Human fetal
      PCCs express the previously reported physiologic responses to activin and inhibin
      generated in nonhuman experiments on gonadotropin secretion in vitro and may
      serve as a physiologic model for studying human gonadotrope responses to the TGF
      beta family of peptides.

PMID- 11594554
TI  - Role of the proteasome in the regulation of fetal fibronectin secretion in human
      placenta.
AB  - The goal of the current study was to examine the role of the ubiquitin-proteasome
      system (UPS), a pathway of intracellular degradation, in the regulation of fetal
      fibronectin (FFN) expression in human placenta. Primary cultures of
      cytotrophoblasts (CTs) and placental mesenchymal cells (PMCs) were isolated from
      human term placentas and were maintained in serum-free medium (SFM) in the
      presence of inhibitors of proteasome-mediated degradation (e.g., MG132) as well
      as inhibitors of other proteases. Levels of secreted FFN and interleukin (IL)-8
      in culture media were quantitated by enzyme-linked immunosorbent assay (ELISA),
      and cell viability was assessed by trypan blue exclusion. Intracellular levels of
      FFN and ubiquinated proteins were measured by Western blotting, and levels of
      fibronectin mRNA were determined following Northern blotting. We found that
      proteasome inhibitors (MG132, MG262, and PSI) potently suppressed levels of
      secreted FFN in cultures of CTs, but they not did affect levels of IL-8.
      Lysosomal, calpain, and serine protease inhibitors as well as the anti
      inflammatory compound sulfasalazine did not markedly affect levels of secreted
      FFN in CT cultures. Proteasome inhibitors did not compromise cell viability
      during the initial 16-18 hours of treatment and did not affect intracellular
      levels of FFN protein or fibronectin mRNA. The efficacy of suppression of FFN in
      CT culture media by proteasome inhibitors reflected their effects on
      intracellular accumulation of ubiquinated proteins. By contrast, the presence of
      proteasome inhibitors did not alter levels of secreted FFN in cultures of PMCs.
      We conclude that inhibitors of proteasome-mediated degradation potently and
      specifically suppressed extracellular expression of FFN in CTs through a cell
      type-specific pathway that did not involve alterations in FFN synthesis. This
      suggests that accumulation of ubiquinated proteins in the presence of proteasome
      inhibitors blocks FFN secretion or promotes the extracellular degradation of FFN.
      This experimental paradigm will be useful for dissecting the role of the UPS in
      regulating CT function.

PMID- 11594555
TI  - The embryo question.
AB  - In Italy, the seat of the Vatican, the problem of the "rights of the embryo" has
      been particularly felt and has caused bitter debate between laymen and clergy.
      The disagreement has focused primarily on the definition of "person,"
      "individual," and the "beginning of life." Catholics, for the most part, have
      contested the concept of the "pre-embryo" and have tried to have a law passed
      that would impede the production and freezing of supernumerary embryos (according
      to the hypothesis of the "simple case"). In the same way, Catholics have strongly
      opposed the possible manipulation of embryos, including pre-implant genetic
      investigations. In addition to Catholic teachings, the National Committee for
      Bioethics has also declared itself favorable to the protection of the "waking
      life." It published a special document on the theme in a period in which the
      Committee was composed only of strict Catholics, following action taken by the
      then Prime Minister, Berlusconi, who believed it necessary to exclude and remove
      all lay members from the Committee. The document of the National Committee for
      Bioethics, which distinguishes itself for having declared that "the embryo is one
      of us," has been the cause of a transversal political aggregation that has
      gathered Catholic parliamentarians from different political parties and that has
      begun a campaign to acknowledge the prerogatives and rights of the embryo which
      Italian law attributes only to the baby after its birth. An intense debate
      continues on all these themes, and in back of all this is the warning from the
      Church to re-examine the Italian law dealing with the voluntary interruption of
      pregnancy.

PMID- 11594556
TI  - Ethical issues in selecting embryos.
AB  - People involved in assisted reproduction frequently make decisions about which of
      several embryos to implant or which of several embryos to reduce from a multiple
      pregnancy. Yet, others have raised questions about the ethical acceptability of
      using sex or genetic characteristics as selection criteria. This paper reviews
      arguments for rejecting embryo selection and discusses the subject of choosing
      offspring in terms of the centrality of liberty and autonomous choice in ethics.
      It also presents a position on the acceptable scope of embryo selection and the
      professional responsibilities of those who practice reproductive medicine.

PMID- 11594557
TI  - Gonadotropin-releasing hormone antagonists implications for oocyte quality and
      uterine receptivity.
AB  - Until recently, gonadotropin-releasing hormone (GnRH) agonists were the only
      choice available to physicians for prevention of premature luteinizing hormone
      (LH) surges in women undergoing controlled ovarian stimulation. The recent FDA
      approval of GnRH antagonists for this indication gives clinicians some new
      options. Results of clinical trials to date suggest that, with GnRH antagonists,
      much shorter treatment regimens with fewer injections and possibly less
      gonadotropin can achieve good clinical results. In most of the trials performed
      to date, however, the GnRH antagonist regimens have been associated with a
      slightly lower pregnancy and implantation rate than the established GnRH agonist
      protocols. This remains the biggest hurdle to their more general acceptance.
      Herein, the possible contributing factors are discussed, and the proposal made
      that differences in serum estradiol patterns preceding oocyte retrieval are the
      most likely contributing factor.

PMID- 11594558
TI  - Ovulation induction disrupts luteal phase function.
AB  - Abnormalities in the luteal phase have been detected in virtually all the
      stimulation protocols used in in vitro fertilization, on both the hormonal and
      endometrial levels. Supraphysiological follicular or luteal sex steroid serum
      concentrations, altered estradiol: progesterone (E2/P) ratio, and disturbed
      luteinizing hormone pituitary secretion leading to corpus luteum insufficiency or
      a direct drug effect have been postulated as the main etiologic factors.
      Luteinizing hormone supports corpus luteum function, and low LH levels have been
      described after human menopausal gonadotropin treatment, after gonadotropin
      releasing hormone (GnRH)-agonist treatment, or after GnRH-antagonist treatment.
      These low luteal LH levels may lead to an insufficient corpus luteum function and
      consequently to a shortened luteal phase or to the low luteal progesterone
      concentrations frequently described after ovulation induction. A direct effect of
      the GnRH agonist or GnRH antagonist on human corpus luteum or on human
      endometrium and thus on endometrial receptivity cannot be excluded, as GnRH
      receptors have been described in both compartments. Endometrial histology has
      revealed a wide range of abnormalities during the various stimulation protocols.
      In GnRH-agonist cycles, mid-luteal biopsies have revealed increased glandulo
      stromal dyssynchrony and delay in endometrial development, strong positivity of
      endometrial glands for progesterone receptors, decreased alphavbeta3-integrin
      subunit expression, and earlier appearance of surface epithelium pinopodes. These
      factors suggest a shift forwards of the implantation window. Progesterone
      supplementation improves endometrial histology, and its necessity has been well
      established, at least in cycles using GnRH agonists.

PMID- 11594559
TI  - Perifollicular vascularity and its relationship with oocyte maturity and IVF
      outcome.
AB  - New markers of embryo ability to implant are pursued continuously. Understanding
      whether an oocyte is really "mature," that is, ready to be fertilized, would be
      of great help in choosing an embryo that will implant. It is usual to pay
      attention to the phase of meiosis, considering the extrusion of the polar body
      (metaphase II) to be the only sign of the maturity of the oocytes. Nevertheless,
      understanding more about how the cytoplasm contributes to an oocyte's competency
      also shows promise as a method of predicting which embryos will implant. Some
      studies about perifollicular vascularity have demonstrated that embryos
      originating from oocytes developed in well-vascularized follicles have a higher
      implantation rate than those originating from oocytes developed in follicles with
      poor vascularization. Here, we report our results from a preliminary study in
      which embryos were transferred according to the degree of vascularization of the
      follicle. Women who received embryos originating from oocytes developed in well
      vascularized follicles had a statistically higher pregnancy rate than women who
      received embryos deriving from oocytes grown in more poorly vascularized
      follicles (34% vs. 13.7%).

PMID- 11594560
TI  - Role of steroid hormone-regulated genes in implantation.
AB  - The endometrium acquires the ability to implant the developing embryo within a
      specific time window, termed the "receptive phase." During this period, the
      endometrium undergoes pronounced structural and functional changes induced by the
      ovarian steroids, estrogen and progesterone, which prepare it to be receptive to
      invasion by the embryo. These steroid-induced molecules, when identified, may
      serve as useful markers of uterine receptivity. In this article, we provide a
      brief description of one such molecule that has emerged as candidate marker of
      steroid hormone action in rats and humans during implantation.

PMID- 11594561
TI  - Decidual cell-expressed tissue factor maintains hemostasis in human endometrium.
AB  - We showed that decidualized stromal cells of luteal phase and pregnant human
      endometrium express tissue factor (TF), the primary initiator of hemostasis,
      thereby suggesting a mechanism by which perivascular decidual cells can mitigate
      the risk of hemorrhage during endovascular trophoblast invasion. Progestins
      enhanced TF mRNA and protein levels in monolayers of human endometrial stromal
      cells (HESCs), with estradiol (E2) + progestin, further enhancing TF levels
      despite a lack of response to E2 alone. This differential ovarian steroid
      response has been found for several decidualization markers. Further studies with
      cultured HESCs established that elevated TF levels are mediated by the
      progesterone receptor and are maintained for weeks in response to E2 plus
      progestin, thus simulating the chronic upregulation of TF levels observed in
      decidualized HESCs in vivo. Recent studies revealed that elevated TF expression
      during in vitro decidualization of HESCs involved both the EGFR and progesterone
      receptor. Thus, enhancement of TF mRNA and protein levels in the HESCs required
      co-incubation with a progestin (MPA) and an EGFR agonist such as EGF or TGF
      alpha. In correspondence with co-elevation of EGFR and TF in decidualized HESCs
      in sections of luteal phase and pregnant endometrium, EGFR levels proved to be
      progestin-enhanced in the cultured HESCs. We established that progestin-enhanced
      TF expression in HESCs was trancriptionally regulated, then evaluated the
      relative roles of SP and EGR-1 sites on the TF promoter in regulating this
      expression. Transient transfections with a series of promoter constructs
      containing overlapping SP and EGR-1 sites and with constructs in which the EGR-1
      and SP sites were systematically inactivated by site-directed mutagenesis
      established the dominance of SP sites in both basal and progestin-enhanced TF
      transcriptional activity. Additional experiments involving transient
      transfections with SPloverexpressing vectors and with a specific blocker of if
      Sp1 binding to its corresponding GC box specified the importance of the Sp1
      transcription factor. These results were further validated by immunostaining,
      which revealed that the ratio of Sp1 to Sp3 increased during progestin-regulated
      decidualization of HESCs in vitro and in vivo. The absence of canonical estrogen
      and progesterone response elements from either the TF or Sp1 gene promoters
      suggests that the EGFR may help to mediate progestin-enhanced TF expression
      during decidualization of HESCs.

PMID- 11594562
TI  - Design and conduct of clinical trials in hormone replacement therapy.
AB  - Postmenopausal hormone replacement therapy represents an area of outstanding
      importance in preventive medicine that greatly affects personal well-being as
      well as public health. The number of women living in the United States who are 50
      years or older has been estimated at nearly 50 million. Many of those women are
      likely to be eligible for postmenopausal hormone replacement, which may consist
      either of estrogen replacement therapy (ERT) in women without a uterus or, more
      frequently, estrogen/progestin combination therapy (HRT) in women with a uterus.
      This chapter first presents an overview of general regulatory requirements
      pertaining to the design and conduct of clinical studies in support of marketing
      approval for a drug product. These requirements include, but are not restricted
      to, studies in HRT. The chapter next discusses the design and conduct of clinical
      trials in support of marketing approval for the indications: treatment of
      moderate to severe vasomotor symptoms and vulvovaginal atrophy; prevention of
      osteoporosis; and protection by adjunctive progestin against estrogen-induced
      endometrial hyperplasia/cancer in women with a uterus. Finally, data related to
      the potential cardioprotective action of HRT and its protection against
      Alzheimer's disease and colon cancer are discussed.

PMID- 11594563
TI  - Cutaneous T cell lymphoma: the helping hand of dendritic cells.
AB  - Since its introduction 25 years ago, cutaneous T cell lymphoma has become the
      preferred designation for clonal malignancies of those CD4 thymus-derived
      lymphocytes ("cutaneous T cells") that preferentially migrate to skin. The varied
      cutaneous clinical presentations, dependent on the specific features of the
      dominant subclones of the malignant lymphocytes, historically led to confusing
      descriptive terms (mycosis fungoides, Sezary syndrome, lymphoma cutis, leukemia
      cutis, reticulum cell sarcoma of the skin). Recognition that all of these
      clinical presentations are cancers of a single type of cell has permitted their
      unification under the single, clarified heading cutaneous T cell lymphoma, or
      CTCL. As a neoplastic amplification of the skin-homing T cells from which it is
      derived, CTCL's distinctive features can be explained. The triad of skin
      localization, remarkable avoidance of bone marrow, often even in the context of
      extremely high leukemic counts, and infiltration of perifollicular T cell zones
      of the lymph nodes and spleen reflect the migratory pathway and homing patterns
      of cutaneous T cells. The usually retained levels of serum immunoglobulins and
      the resulting capacity to defend against encapsulated bacteria, often even in
      advanced CTCL, are manifestations of the helper function of the malignant T cells
      that is, their functional capacity to stimulate B lymphocytes to produce
      immunoglobulin in a polyclonal manner. In contrast, the often-extreme normal T
      cell deficits in advanced CTCL, equivalent to those of late-stage AIDS, probably
      resulting from the production of suppressive cytokines such as IL-10, cause
      susceptibility to a broad range of opportunistic infections, the most common
      direct cause of death. Pautrier microabscesses, the pathognomonic feature of
      epidermotropic early CTCL, hold the clues to the pathogenesis of the cancer.
      These intraepidermal collections of stimulated and proliferating malignant cells,
      adherent to the dendrites of intraepidermal dendritic antigen-presenting cells
      (Langerhans' cells [LCs]), indicate a dynamic communication between the two cell
      types. Since CTCL cells are derived from CD4 T cells, which normally receive
      signaling from dendritic cells (DCs) via presentation of antigenic peptides as
      part of class II major histocompatibility complexes to antigen-specific T cell
      receptors (TCRs), it seems likely that CTCL is a clonal proliferation of T cells
      responding to specific antigenic stimulation from LCs. This is supported by our
      recent finding that CTCL cells proliferate in vitro in response to TCR
      stimulation by autologous DCs, which have previously ingested and processed
      antigens from apoptotic autologous CTCL cells. In short, CTCL may be a malignancy
      of T cells stimulated to proliferate against its own tumor antigens. The most
      intriguing possibility is that a yet-unidentified transforming retrovirus,
      harbored by LCs, simultaneously attracts, stimulates, and transforms a single
      clone of antigen-specific cutaneous T cells. Longstanding disease-free remissions
      have been induced by transimmunization (via a photopheresis apparatus). This
      treatment, introduced more than a decade ago by our group and the first and still
      the only FDA-approved selective anticancer immunotherapy, has been performed more
      than 200,000 times worldwide on advanced CTCL, as well as in reversal/prevention
      of heart transplant rejection and treatment of graft-versus-host disease and
      selected autoimmune disorders. Transimmunization induces clinically relevant
      suppression, and occasionally elimination, of pathogenic T cell clones. The
      common denominator between these diverse groups of responding patients is the
      presence of clonally distinctive TCRs on the disease-causing malignant or
      autoaggressive T cell clones. In CTCL at least one source of tumor-specific
      antigens is derived from the clone-specific (idiotypic) segments of the TCR
      protein chains. In the photopheresis apparatus, two synergistic phenomena are
      initiated: induction of apoptosis of the CTCL cells and mass conversion of blood
      monocytes to DCs. The young DCs then ingest the apoptotic CTCL cells, process and
      present the CTCL antigens to responding anti-CTCL cytotoxic T cells, and
      stimulate clinically important CTCL suppression. Now that it is better
      understood, transimmunization may have much broader applications in other types
      of cancer as well.

PMID- 11594564
TI  - The clonotypic T cell receptor is a source of tumor-associated antigens in
      cutaneous T cell lymphoma.
AB  - To develop cancer vaccines for the treatment of cutaneous T cell lymphoma (CTCL),
      immunogenic peptides were identified by two approaches. First, through the use of
      "reverse immunology" the peptide sequence of the idiotypic region of the beta
      chain of the T cell receptor (TCR) was determined and a series of overlapping
      peptides synthesized and tested for CD8 T cell recognition. In two patients, the
      idiotypic CDR3 region provided immunogenic epitopes that were recognized in a
      class I-restricted fashion by autologous CD8 T cell lines. In a second strategy,
      peptides were isolated directly from class I MHC molecules on the CTCL surface
      and sequenced. A peptide with partial homology to sequences contained in the
      conserved variable portion of the clonotypic TCR beta chain was recognized as
      immunogenic by autologous CD8 T cells. Therefore, both approaches demonstrated
      that the clonotypic TCR in CTCL is a source of immunogenic tumor epitopes. To
      confirm that recognition of TCR-derived sequences provides immunoprotection
      against tumor growth, a murine model of T cell lymphoma was studied. The
      immunogenicity of a thymoma, which lacks cell surface TCR expression, was
      enhanced by transfection of the beta chain of the TCR. The studies reviewed in
      this paper demonstrate that the TCR can serve as one source for immunogenic tumor
      peptides in T cell lymphoma in vitro and in vivo. Presentation of TCR epitopes on
      dendritic cells that express high levels of MHC, costimulatory, and adhesion
      molecules may provide an effective means for immunization against T cell
      malignancy.

PMID- 11594565
TI  - Human endothelial cell presentation of antigen and the homing of memory/effector
      T cells to skin.
AB  - Dermal microvascular endothelial cells (ECs) form a continuous lining that
      normally bars blood-borne T lymphocytes from entering the skin, but as part of
      the response to foreign antigen, dermal ECs undergo alterations in their surface
      proteins so as to provide signals to circulating T cells that lead to their
      activation and recruitment. Several observations suggest that human dermal
      microvascular ECs may help initiate cutaneous immune reactions by presentation of
      cognate antigens to circulating T memory cells: (1) antigen-specific inflammatory
      responses in the skin, as in other organs, involve accumulation of memory and
      effector T cell populations that are enriched in cells specific for the eliciting
      antigen; (2) recall responses to intradermal protein antigens in the skin start
      very rapidly within two hours of challenge; (3) dermal microvascular ECs in
      humans and other large mammals basally display high levels of class I and class
      II MHC molecules, the only known purpose of which is to present antigenic
      peptides to lymphocytes; (4) the lumen of dermal capillaries are narrower than
      the diameter of circulating T cells, ensuring surface contact; and (5) cultured
      human ECs effectively present antigens to resting memory T cells isolated from
      the circulation. Upon contact with activated T cells or their secreted products
      (cytokines), dermal ECs themselves become activated, increasing their capacity to
      recruit memory and effector T cell populations in an antigen-independent manner.
      Specifically, activated ECs express inducible leukocyte adhesion molecules such
      as E-selectin, ICAM-1, and VCAM-1; and several lines of evidence, including
      neutralizing antibody experiments and gene knockouts, have supported a role of
      these molecules in T cell recruitment. Dermal ECs have unique expression patterns
      of adhesion molecules that can determine the subsets of memory T cells that are
      recruited into the skin. For example, slow internalization of E-selectin allows
      more persistent expression of this protein on the surface of dermal ECs, favoring
      interactions with CLA-1+ T cells. VCAM-1 expression, normally confined to venular
      EC may extend to capillaries within the dermal papillae and contribute to
      epidermal inflammation, recruiting alpha4beta7 integrin-expressing T cells that
      also express the cadherin-binding integrin alphaEbeta7. New models involving
      transplantation of normal and genetically modified human dermal ECs into
      immunodeficient mice may be used to further explore these properties.

PMID- 11594566
TI  - Extracorporeal photochemoimmunotherapy in cutaneous T cell lymphomas.
AB  - Extracorporeal photochemotherapy (ECP), or photopheresis, is a widely used
      treatment for cutaneous T cell lymphoma (CTCL) and other T cell-mediated
      disorders, having been administered in more than 150 centers worldwide more than
      200,000 times. Consistent with the theme of this conference--that is,
      highlighting the potentially most productive investigative avenues for unraveling
      the mysteries of CTCL in the next decade--ECP has been futuristic since its
      inception in the early 1980s. In 1988, the treatment was the first FDA-approved
      selective immunotherapy for any type of cancer. Yet, the mechanism by which it
      could suppress a clone of CTCL cells or inactivate multiple autoreactive T cell
      clones in graft-versus-host disease (GVHD) or allograft rejection remained
      obscure until quite recently. In fact, the scientific principles necessary to
      begin to comprehend the basis of ECP's efficacy were not available when the
      treatment was first introduced in 1982. In the intervening years, necessary
      detailed knowledge of the structure and function of the clonotypic T cell
      receptors, of class I major histocompatibility complex (MHC) presentation of
      tumor antigens, of CTCL tumor-specific antigens, of dendritic antigen presenting
      cell (DC) biology, and of 8-methoxypsoralen immunopharmacology has been attained.
      Although much remains to be learned, we now appreciate that ECP simultaneously
      and efficiently induces both apoptosis of disease-causing T cells and conversion
      of monocytes to functional DCs. By processing and presenting the unique antigenic
      determinants of pathogenic T cell clones, the DCs can either initiate a
      clinically relevant anti-CTCL cytotoxic response or suppress the activity of
      autoreactive T cell clones. This paper will review clinical trials of ECP in CTCL
      and evolving scientific understanding of ECP's mechanism in the context of
      exciting future directions.

PMID- 11594567
TI  - Percutaneous peptide immunization via corneum barrier-disrupted murine skin for
      experimental tumor immunoprophylaxis.
AB  - Percutaneous peptide immunization is a method in which tumor-specific cytotoxic T
      lymphocytes (CTL) are primed in the lymph nodes and spleen following application
      of tumor peptides to corneum barrier-disrupted murine skin. Immunized mice are
      protected against subsequent challenge with corresponding tumors and suppress the
      growth of established tumors. CTL expansion after peptide application seems to be
      mediated by epidermal Langerhans' cells. In the human, disruption of permeability
      barrier by tape stripping also induces activation of epidermal Langerhans' cells.
      Thus, percutaneous peptide immunization provides a simple and noninvasive means
      of inducing potent antitumor immunity that may be exploited for cancer
      immunotherapy in the human.

PMID- 11594568
TI  - Autologous peripheral blood stem cell transplantation in tumor-stage mycosis
      fungoides: predictors of disease-free survival.
AB  - Nine patients with mycosis fungoides (age range 27-67) underwent autologous
      peripheral blood stem cell transplantation (PBSCT). All patients had tumor-stage
      disease, and four had lymph node involvement. Eight patients exhibited a
      peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six
      prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells
      was achieved with etoposide and G-CSF. Harvested cells were positively selected
      for CD34. After negative selection for CD4 and CD8, only two samples became PCR
      negative. Conditioning prior to reinfusion of stem cells was achieved with
      various combinations of total skin electron beam (TSEB), total body irradiation
      (TBI), and chemotherapy, depending upon the patient's prior exposure to
      radiotherapy. One patient failed to engraft and died of candidal septicemia 15
      days posttransplant. The other eight patients achieved complete remission, but
      this was short-lived in four (median disease-free survival [DFS] = 2 months) and
      prolonged in three (median DFS 11 months). Those with a short DFS were
      distinguished by rapid tumor onset prior to transplant but not by stage at
      transplant. Loss of a detectable T cell clone after manipulation of the harvest
      did not discriminate between the two groups, but rapid relapsers had been
      subjected to a greater degree of T cell depletion, possibly indicating a
      compromised cytotoxic response post-PBSCT. The median survival of the cohort is
      four years from tumor onset, 15 months from PBSCT, and 27 months from the date a
      peripheral blood clone was first detected in the presence of tumor-stage disease.
      Rapid relapse was associated with poor overall survival. Our data demonstrate the
      value of PBSCT for inducing remission in tumor-stage mycosis fungoides.
      Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an
      earlier stage in the disease process, preferably before a T cell clone is
      detectable in the peripheral blood. Alternatively T cell depletion should be
      restricted to the CD4 subset.

PMID- 11594569
TI  - Clinical trials and efficacy assessment in the therapy of cutaneous T cell
      lymphoma.
AB  - The ability of clinical trials to measure cutaneous T cell lymphoma (CTCL) has
      allowed physicians and regulatory reviewers to assess the response of the disease
      to experimental therapies. The goals of therapy are remission, palliation, and
      improvement of survival. Given the chronic nature of the disease, surrogate
      markers for survival are used in clinical trials. The surrogate markers and the
      validity of the surrogate markers used to date will be compared and contrasted.
      Tumor burden measurements by way of skin scoring are the parameters most commonly
      used to assess the response to therapy. Skin scoring systems have used global
      mapping, severity recording, or target lesions to assess any change in response
      to an intervention. The advantages and limitations of global and focal scoring
      are presented, along with examples of skin scoring systems for the five most
      recently completed trials for CTCL. Measures of palliation are performed via
      questionnaires. General and CTCL-specific questionnaires have been developed that
      assess both discrete and global manifestations of the disease. Those measures of
      palliation that have been shown to correlate with skin scoring are presented for
      inclusion into future studies. In addition, study terms such as relapse and
      freedom from relapse can now be defined with reproducible molecular techniques.
      Every stage of CTCL warrants further clinical trials, and guidelines for future
      investigations are proposed.

PMID- 11594570
TI  - Interleukin-2 fusion toxin: targeted therapy for cutaneous T cell lymphoma.
AB  - The interleukin (IL)-2 receptor has proved an attractive target for T cell
      directed therapies. Agents including monoclonal antibodies, single-chain antibody
      immunoconjugates, radioimmunoconjugates, and, most recently, ligand fusion toxins
      have demonstrated activity in vitro and in clinical trials in both hematologic
      malignancies and diseases characterized by proliferation of activated T cells,
      such as graft-versus-host disease. DAB389IL-2 (ONTAK) is a ligand fusion toxin
      consisting of the full-length sequence of the IL-2 gene genetically fused to the
      enzymatically active and translocating domains of diphtheria toxin. DAB389IL-2
      and its predecessor, DAB486IL-2, have demonstrated activity in a variety of
      diseases, including cutaneous T cell lymphoma (CTCL), psoriasis, rheumatoid
      arthritis, and HIV infection. Further clinical development of IL-2 fusion toxins
      in CTCL and other hematopoietic malignancies is predicated on identification of
      the high-affinity IL-2 receptor complex on the malignant cells and on a better
      understanding of the biological determinants of cytotoxicity of these molecules
      in vivo.

PMID- 11594571
TI  - The role for interleukin-12 therapy of cutaneous T cell lymphoma.
AB  - Recent phase I and phase II trials using recombinant human interleukin-12 (rhIL
      12) for cutaneous T cell lymphoma (CTCL) have been completed. Observations on 32
      evaluable patients revealed an overall response rate approaching 50 percent.
      Biopsy of regressing lesions revealed an increase in numbers of CD8+ and/or TIA
      1+ T cells. These results suggest that rhIL-12 may induce lesion regression by
      augmenting antitumor cytotoxic T cell responses. Future trials will be focused on
      strategies for further immune enhancement by the concomitant use of additional
      immune augmenting cytokines with rhIL-12.

PMID- 11594573
TI  - Apoptosis and cutaneous T cell lymphoma.
AB  - The most successful therapies in the treatment of cutaneous T cell lymphoma
      (CTCL), which include localized X-ray therapy, total skin electron beam therapy,
      total skin therapy with psoralen and UVA or other forms of UV light therapy,
      topical chemotherapy, and even topical steroids, all work by inducing T cell
      apoptosis. Yet, these same malignant T cells, which readily undergo apoptosis
      after these therapies, are far less likely to do so after therapy with systemic
      chemotherapeutic agents that are often curative in B cell lymphomas. Apoptosis in
      T cells is a normal phenotype in that only a small fraction of nonneoplastic T
      cells fail to undergo apoptosis. Although we still understand relatively little
      regarding the molecular biology of CTCL, it is clear that the neoplastic cell
      clone or clones that predominate in this disease have defects in normal apoptotic
      control mechanisms. These can be overridden in most cases by the strong
      proapoptotic signals triggered by ionizing radiation and other agents. Better
      understanding of the mechanisms by which the latter occurs should help us both
      improve our current therapies and devise new ones.

PMID- 11594572
TI  - Photoactivational cytokine-modulatory action of 8-methoxypsoralen plus
      ultraviolet A in lymphocytes, monocytes, and cutaneous T cell lymphoma cells.
AB  - Treatment with 8-methoxypsoralen (8-MOP) and ultraviolet A light (UVA) has been
      reported to modulate cytokine production in various cells. Our study was
      conducted to see the effects of 8-MOP/UVA on the expression/production of
      cytokines in peripheral blood lymphocytes and monocytes in relation to the
      therapeutic mechanisms of extracorporeal photochemotherapy. 8-MOP/UVA augmented
      the expression of mRNAs for interferon-gamma (IFN-gamma) and interleukin (IL)-2
      and reduced those for IL-4 and IL-10 in peripheral blood mononuclear cells
      (PBMCs) from normal subjects and Sezary syndrome patients. This enhancement of
      Th1 cytokines was caused by increment of cytokine production by Th1 cells but not
      by conversion of Th2 cells to produce Th1 cytokines. The number of IFN-gamma
      secreting lymphocytes was markedly increased in 8-MOP/UVA-treated PBMCs 20 h
      after treatment, and its amount was elevated in culture supernatants. However,
      this enhanced production of IFN-gamma was found only until three days after 8-MOP
      phototreatment, and its level was rapidly declined by five days after treatment.
      In addition to this Th1-polarized action, 8-MOP/UVA-treated PBMCs produced
      enhanced amounts of IL-8 upon stimulation with anti-CD3/CD28 antibodies.
      Phototreated CD4+ but not CD8+ cells provided excellent T cell help for monocytes
      to produce IL-8 via a direct cell-to-cell contact mechanism. These findings
      suggest that 8-MOP/UVA has a transient but biologically active Th1-skewing action
      in T cells, and the phototreated T cells simultaneously stimulate monocytes to
      produce IL-8. It is suggested that 8-MOP/UVA exerts a beneficial therapeutic
      effect on malignant Th2 neoplasms as a Th1-skewing cytokine modifier and that 8
      MOP-phototreated CD4+ T cells allow monocytes to become effective tumor antigen
      presenting cells for tumor-specific cytotoxic T cells.

PMID- 11594574
TI  - Therapy of T cell lymphomas with pentostatin.
AB  - Pentostatin is a highly lymphocytotoxic agent active in hairy cell leukemia.
      Several studies also suggest significant activity in T cell lymphomas manifested
      in the skin. Herein, we will review the studies of pentostatin in these lymphomas
      and our most recent trial of this agent in heavily pretreated patients with
      cutaneous and peripheral T cell lymphomas. Overall, the data suggest that
      pentostatin has significant antitumor activity in these patients, with response
      rates ranging from 33% to over 70%. Approximately one-third of the responses are
      complete. The most common side effects include granulocytopenia, nausea, and
      renal insufficiency. CD4 suppression occurs and may result in an increased risk
      of herpes zoster infection. Although prolonged remissions have been seen, most
      responses are short-lived. These observations suggest that further exploration of
      this agent, in combination with other drugs active in T cell lymphomas, is
      warranted in this group of diseases.

PMID- 11594575
TI  - The effect of insulin-dependent diabetes mellitus on the efficacy of
      extracorporeal photopheresis in late-stage Sezary syndrome.

PMID- 11594576
TI  - Treatment of cutaneous T cell lymphoma stage II with interferon-alpha-2a and
      extracorporeal photochemotherapy: a prospective controlled trial.

PMID- 11594577
TI  - Pegylated doxorubicin for primary cutaneous T cell lymphoma: a report on ten
      patients with follow-up.

PMID- 11594578
TI  - Survival of patients with cutaneous T cell lymphoma after treatment with
      extracorporeal photochemotherapy: a retrospective single-center analysis.

PMID- 11594579
TI  - Analysis of clonality in cutaneous T cell lymphoma and associated diseases.
AB  - The T cell receptor (TCR) is the antigen-specific receptor for T cells. During
      its differentiation, each T cell undergoes rearrangement of its TCR genes. This
      results in novel nucleotide sequences that constitute a unique signature or
      fingerprint for each T cell and all its clonal progeny. Analysis of TCR gene
      rearrangements in cutaneous T cell lymphoma (CTCL) has lead to several findings
      concerning CTCL tumor biology. First, like most other lymphomas, CTCL is a
      monoclonal lymphoproliferative disorder. Second, rather than being truly a
      cutaneous lymphoma, CTCL is actually a lymphoma of the skin-associated lymphoid
      tissue (SALT). Even when disease appears confined to the skin clinically, there
      can be low-level trafficking of tumor cells through the peripheral lymph nodes
      via the lymphatics and blood vessels. Furthermore, CTCL is a mature SALT lymphoma
      capable of trafficking to sites of cutaneous inflammation analogous to normal
      SALT T cells. Third, the earliest manifestation of CTCL may be "clonal
      dermatitis." This is a form of chronic dermatitis that harbors a dominant T cell
      clone but lacks histologic features diagnostic for CTCL. About 25% of clonal
      dermatitis cases progress to overt CTCL within five years. Fourth, other
      lymphoproliferative disorders that are associated with CTCL share the same TCR
      gene rearrangements and therefore arise as subclones of the original tumor. These
      include lymphomatoid papulosis, large-cell lymphoma, and Hodgkin's disease.

PMID- 11594580
TI  - Crosstalk between tumor T lymphocytes and reactive T lymphocytes in cutaneous T
      cell lymphomas.
AB  - We have established several tumor T cell lines, both from the skin and from the
      blood of a patient with an MHC class II-/class I+, CD4+ cutaneous T cell lymphoma
      (CTCL). These cell lines, like the initial tumor cells, had a CD3+CD4+CD8-
      phenotype. We also isolated two cytotoxic T lymphocyte clones from the tumor site
      of this CTCL patient. These clones displayed a CD4+CD8dim+ (TC5) and CD4+CD8-
      (TC7) phenotype and mediated a specific MHC class I-restricted cytotoxic activity
      toward noncultured tumor cells and autologous tumor cell lines. Despite surface
      expression of Fas on tumor cells and Fas-L induction on TC5 and TC7 cell membrane
      after coculture with autologous tumor cells, the CD4+ CTL clones did not use this
      cytotoxic mechanism to lyse their specific target. TC7 used a granzyme/perforin
      dependent pathway, whereas TC5 used a TRAIL-dependent mechanism. Quantitative
      analysis of cytokine mRNA expression indicated that while the tumor cells
      displayed a Th2-type profile, the CTL clones expressed Th1-type cytokines.
      Preincubation of TIL clones with autologous tumor cells in a short-term culture
      induced their activation and subsequent amplification of the Th1-type response,
      which indicates a direct contribution of the malignant cells in the Th1/Th2
      imbalance. However, we found that tumor cells produced high amounts of TGF-beta,
      which could explain the inhibition of a specific antitumor immune response.
      Another mechanism to avoid the host immune response was the expression of CD158a,
      CD158b, p70, and CD94/NKG2A inhibitory receptors by tumor-specific lymphocytes.
      Finally, we present recent data on new antigen structures expressed both by long
      term CTCL lines and uncultured tumor cells.

PMID- 11594581
TI  - Molecular genetics of cutaneous lymphomas.
AB  - The underlying molecular basis of primary cutaneous lymphomas has not yet been
      clarified. However, abnormalities of cell cycle control genes and well-defined
      tumor suppressor genes such as p53 are common and may contribute to disease
      progression and treatment resistance. Biallelic inactivation of tumor suppressor
      genes usually occurs by a combination of deletion, point mutation, and/or
      promotor hypermethylation. The detection of UVB-specific mutations of p53
      requires confirmation but may have important implications for the management of
      patients with mycosis fungoides. Molecular cytogenetic studies have identified
      common regions of chromosomal deletion and amplification, which suggests the
      presence and location of genes that are of critical importance in the
      pathogenesis of cutaneous lymphoma.

PMID- 11594582
TI  - Reversible resistance to apoptosis in cutaneous T cell lymphoma.
AB  - Mycosis fungoides and its leukemic variant, Sezary syndrome, represent the most
      common forms of cutaneous T cell lymphomas (CTCL). These disorders are clonal
      neoplasms characterized by the progressive accumulation of cells that resemble
      activated/memory CD4+ T cells. Unlike their normal counterparts, these malignant
      lymphocytes have prolonged life spans and are resistant to dying following
      treatment with most chemotherapeutic agents. This suggests that CTCL undergo
      abnormal programmed cell death; however, data regarding apoptotic defects in CTCL
      are limited. Regulation of apoptosis in lymphocytes that regularly undergo clonal
      expansion is necessarily complex and will be reviewed here. Clonally expanded
      lymphocytes rely primarily on Fas-mediated pathways to initiate apoptosis.
      Factors leading to the resistance of apoptosis in CTCL and new therapeutic
      approaches for reversing this resistance will be discussed, including the
      important role that the Fas death pathway may play in the pathogenesis and
      treatment of CTCL.

PMID- 11594583
TI  - Progression of lymphomatoid papulosis to systemic lymphoma is associated with
      escape from growth inhibition by transforming growth factor-beta and CD30 ligand.
AB  - Our objective is to understand the mechanism of progression of lymphomatoid
      papulosis (LyP) to CD30+ systemic lymphoma. LyP lesions appear in recurrent crops
      that regress, only to reappear at a later date in the same or different
      locations. About 10% of patients develop systemic lymphoma. Because transforming
      growth factor-beta (TGF-beta) and CD30 ligand inhibit the growth of normal
      lymphocytes and can be detected in regressing lesions of LyP, we tested the
      effect of these cytokines on cell lines clonally derived from LyP in the
      progression to systemic lymphoma. TGF-beta failed to inhibit the growth of
      lymphoma cells from advanced disease due to mutations of the TGF-beta receptor
      complex that prevented binding of the ligand to tumor cells. A CD30 ligand
      agonist antibody caused proliferation of tumor cells from one patient and had no
      effect on tumor cells of another. In contrast, a Fas agonist antibody caused
      significant growth inhibition of all cell lines. The results suggest that
      progression of LyP to lymphoma is associated with escape of lymphoma cells from
      growth regulation by TGF-beta and CD30 ligand.

PMID- 11594584
TI  - Association between Sezary T cell-activating factor, Chlamydia pneumoniae, and
      cutaneous T cell lymphoma.
AB  - Sezary T cell-activating factor (SAF) was originally defined as an inducer of
      functional interleukin-2 (IL-2) receptors on normal and malignant T cells in
      patients suffering from Sezary syndrome. In fact, a combination of SAF and IL-2
      stimulated the propagation of T cell lines from the peripheral blood mononuclear
      cells (PBMC) of those patients, with approximately one third of those cell lines
      containing the predominant malignant clone as determined via cytogenetic and/or T
      cell receptor gene rearrangement analysis. Although the primary source of SAF was
      mitogen-stimulated PBMC of a patient with Sezary syndrome, we were unable to
      isolate the gene encoding SAF from eukaryotic libraries. However, we observed SAF
      activity in the cytoplasm of one of the malignant cell lines in a complex
      containing RNA and DNA. This observation led us to consider the possibility that
      SAF is not of eukaryotic origin. Intracellular pathogens replicate in the
      cytoplasm of host cells and contain proteins, DNA, and RNA. Using a panel of
      antichlamydial antibodies with confirmation from polymerase chain reaction
      primers, we found that most patients with mycosis fungoides were positive for
      these determinants. Immunoelectron microscopy and protein blotting further
      confirmed antibody reactivity. We showed that Chlamydia pneumoniae were capable
      of infecting normal human keratinocytes in culture. We also demonstrated that C.
      pneumoniae antigen expression was associated with active disease because these
      determinants were not expressed after psoralen and ultraviolet A therapy. We
      hypothesize that chronic infection by C. pneumoniae leads to expansion of C.
      pneumoniae-specific T cells, thereby potentiating the development of cutaneous T
      cell lymphoma.

PMID- 11594585
TI  - The role of human T cell lymphotropic virus type I tax in the development of
      cutaneous T cell lymphoma.
AB  - Although it has been well established that the human T cell lymphotropic virus
      type I (HTLV-I) causes adult T cell leukemia/lymphoma (ATLL) in regions of the
      world where this virus is endemic, its role in the pathogenesis of cutaneous T
      cell lymphoma (CTCL) in the Western world has been less well established. Most
      patients with CTCL are negative for antibodies to the structural proteins of HTLV
      I, and thus a causative role for this virus is usually dismissed. However, the
      Tax sequence of HTLV-I has been found in the peripheral blood mononuclear cells
      of practically all patients with CTCL. Such patients express Tax mRNA and have
      antibodies to p40Tax, the protein encoded by this sequence. Sequence analysis of
      a 159-bp region of Tax extracted from CTCL cells proved to be homologous with the
      same region prepared from a cell line infected with prototypic HTLV-I. By in situ
      PCR, Tax has been demonstrated in the lymphocytes infiltrating the skin as well
      as in the keratinocytes of such patients. Apart from the pathophysiologic and
      clinical interest of these studies, these observations may have therapeutic
      implications. In vitro, the proliferation of HTLV-I-transformed cells can be
      inhibited by antisense to HTLV-I Tax. Since Tax has not been identified in the
      normal human genome, antisense to Tax deserves serious consideration as a
      treatment modality for patients whose cells have been demonstrated to harborTax.

PMID- 11594586
TI  - T cell antigen receptor vaccines for active therapy of T cell malignancies.
AB  - T cell lymphoproliferative disorders continue to be serious management problems,
      and so alternative therapeutic modalities are continuously being explored. One
      such strategy involves immunotherapy using the T cell receptor (TCR) as a target.
      Specifically we are attempting to develop a T cell receptor idiotype (TCR-Id)
      vaccine because the TCR-Id can serve as a tumor-specific antigen. In this article
      we will briefly review the rationale for TCR-Id vaccines, the preclinical models
      as developed in our laboratory, and a discussion of our current plans for a
      vaccine trial in mycosis fungoides.

PMID- 11594587
TI  - Validation of publication of new names and new combinations previously
      effectively published outside the IJSEM.

PMID- 11594588
TI  - Notification that new names and new combinations have appeared in volume 51, part
      4, of the IJSEM.

PMID- 11594589
TI  - Halomonas maura sp. nov., a novel moderately halophilic, exopolysaccharide
      producing bacterium.
AB  - Four moderately halophilic, exopolysaccharide-producing bacterial strains
      isolated from soil samples collected from a saltern at Asilah (Morocco) are
      reported. These four strains were initially considered to belong to the genus
      Halomonas. Their DNA G+C contents varied between 62.2 and 64.1 mol %. DNA-DNA
      hybridization revealed a considerable degree of DNA-DNA similarity amongst all
      four strains (75.5-80.8%). Nevertheless, similarity with the reference strains of
      phylogenetically close relatives was lower than 40%. 16S rRNA gene sequences were
      compared with those of other species of Halomonas and other gram-negative
      bacteria and they were sufficiently distinct phylogenetically from other
      recognized Halomonas species to warrant their designation as a novel species. The
      name Halomonas maura sp. nov. is therefore proposed, with strain S-31T (= CECT
      5298T= DSM 13445T) as the type strain. The fatty acid composition of strain S-31T
      revealed the presence of 18:1omega7c, 16:1omega7c/2-OH i15:0 and 16:0 as the
      major components. Growth rate analysis showed that strain S-31T had specific
      cationic requirements for Na+ and Mg2+.

PMID- 11594590
TI  - New approach to phylogenetic analysis of the genus Bifidobacterium based on
      partial HSP60 gene sequences.
AB  - The partial 60 kDa heat-shock protein (HSP60) genes of 36 Bifidobacterium strains
      representing 30 different Bifidobacterium species and subspecies and of the type
      strain of Gardnerella vaginalis were cloned and sequenced using a pair of
      universal degenerate HSP60 PCR primers. The HSP60 DNA sequence similarities were
      determined for the taxa at various ranks as follows: 99.4-100% within the same
      species, 96% at the subspecies level, and 73-96% (mean 85%) at the interspecies
      level (and 98% in the case of two groups of closely related species,
      Bifidobacterium animalis and Bifidobacterium lactis, Bifidobacterium infantis,
      Bifidobacterium longum and Bifidobacterium suis, whose 165 rRNA sequence
      similarities are all above 99%). The HSP60 DNA sequence similarities between
      different Bifidobacterium species and G. vaginalis, a closely related bacterium
      according to 16S rRNA analysis, ranged from 71 to 79% (mean 75%). Although the
      topology of the phylogenetic tree constructed using the HSP60 sequences
      determined was basically similar to that for 16S rRNA, it seemed to be more clear
      cut for species delineation, and the clustering was better correlated with the
      DNA base composition (mol% G+C) than that of the 16S rRNA tree. In the HSP60
      phylogenetic tree, all of the high-G+C (55-67 mol%) bifidobacteria were grouped
      into one cluster, whereas the low-G+C species Bifidobacterium inopinatum (45 mol
      %) formed a separate cluster with G. vaginalis (42 mol%) and Bifidobacterium
      denticolens (55 mol%); a Bifidobacterium species of intermediate G+C content
      formed another cluster between the two. This study demonstrates that the highly
      conserved and ubiquitous HSP60 gene is an accurate and convenient tool for
      phylogenetic analysis of the genus Bifidobacterium.

PMID- 11594591
TI  - Phylogenetic analysis and taxonomic study of marine Cytophaga-like bacteria:
      proposal for Tenacibaculum gen. nov. with Tenacibaculum maritimum comb. nov. and
      Tenacibaculum ovolyticum comb. nov., and description of Tenacibaculum mesophilum
      sp. nov. and Tenacibaculum amylolyticum sp. nov.
AB  - Bacterial strains were isolated from sponge and green algae which were collected
      on the coast of Japan and Palau. The phylogenetic relationships of these isolates
      among marine species of the Cytophaga-Flavobacterium-Bacteroides complex were
      analysed by using their gyrB nucleotide sequences and translated peptide
      sequences (GyrB) in addition to 16S rDNA sequences. These isolates were closely
      related to the previously characterized marine Flexibacter species, [Flexibacter]
      maritimus and [Flexibacter] ovolyticus. These Flexibacter species are distantly
      related to Flexibacter flexilis, the type species of the genus Flexibacter, and
      phylogenetically belong to the family Flavobacteriaceae (according to analysis
      using both 16S rDNA and GyrB sequences). Their phylogenetic, chemotaxonomic and
      phenotypic characteristics prompted the proposal that these two species should be
      transferred to the new genus Tenacibaculum, as Tenacibaculum maritimum and
      Tenacibaculum ovolyticum, respectively. Two additional new species of the genus
      Tenacibaculum, Tenacibaculum mesophilum gen. nov., sp. nov. (= MBIC 1140T = IFO
      16307T) and Tenacibaculum amylolyticum gen. nov., sp. nov. (= MBIC 4355T = IFO
      16310T), which were isolated from sponges and macroalgae, are also reported. For
      taxonomic considerations at the species level, the resolution of gyrB sequences
      was superior to that of 16S rDNA sequences, and the grouping based on the gyrB
      phylogram was consistent with DNA-DNA hybridization results.

PMID- 11594592
TI  - Salana multivorans gen. nov., sp. nov., a novel actinobacterium isolated from an
      anaerobic bioreactor and capable of selenate reduction.
AB  - Three facultatively anaerobic, Gram-positive bacteria, strains Se-3111T, Se-13111
      and Se-1311A, were isolated from an anaerobic, dechlorinating bioreactor culture
      enriched from sediment of the River Saale in Germany. All strains were isolated
      from the dechlorinating mixed culture through their ability to reduce selenate
      anaerobically to elemental selenium. All three strains shared identical 16S rDNA
      sequences and phylogenetic analysis revealed that strain Se-3111T forms a novel
      taxon within the suborder Micrococcineae of the class Actinobacteria, related
      most closely to Beutenbergia cavernae. On the basis of genotypic, chemotaxonomic
      and physiological characteristics, it is proposed that the novel strains Se
      3111T, Se-13111 and Se-1311A be classified in a new genus as Salana multivorans
      gen. nov., sp. nov. The type strain of the novel species is Se-3111T (= DSM
      13521T = NRRL B-24118T).

PMID- 11594593
TI  - Methanoculleus chikugoensis sp. nov., a novel methanogenic archaeon isolated from
      paddy field soil in Japan, and DNA-DNA hybridization among Methanoculleus
      species.
AB  - A strictly anaerobic, irregularly coccoid, methanogenic archaeon, strain MG62T (=
      JCM 10825T = DSM 13459T), was isolated from paddy field soil in Chikugo, Fukuoka,
      Japan. The cells stained gram-negative, were 1.0-2.0 microm in diameter, were
      lysed by SDS and hypotonic solutions and were flagellated. Motility was not
      observed. The strain was able to use H2/CO2, 2-propanol/CO2, formate, 2
      butanol/CO2 and cyclopentanol/CO2 as substrates for methanogenesis, but did not
      utilize acetate, ethanol, methanol or methylamines. The optimum temperature and
      pH were 25-30 degrees C and 6.7-7.2. Analysis of lipid component parts (core
      lipids, phospholipid polar head groups and glycolipid sugar moieties) showed the
      characteristic pattern of members of the family Methanomicrobiaceae except for
      the absence of glucose as a glycolipid sugar moiety. The G+C content of the DNA
      was 62.2 mol %. Sequence analysis of the 16S rDNA revealed that the strain
      belonged to the genus Methanoculleus. The strain had DNA-DNA hybridization values
      of less than 50% with type strains of Methanoculleus species. On the basis of
      phenotypic, genotypic and phylogenetic characteristics, the name Methanoculleus
      chikugoensis sp. nov. is proposed for strain MG62T (= JCM 10825T = DSM 13459T).
      The DNA hybridization study also revealed the close relationships of three
      species, Methanoculleus olentangyi, Methanoculleus bourgensis and Methanoculleus
      oldenburgensis, among Methanoculleus species.

PMID- 11594594
TI  - Bacillus sonorensis sp. nov., a close relative of Bacillus licheniformis,
      isolated from soil in the Sonoran Desert, Arizona.
AB  - Eight Bacillus strains isolated from Sonoran Desert soil were shown to belong to
      a previously unidentified species, for which the name Bacillus sonorensis sp.
      nov. is proposed. The type strain is strain L87-10T (= NRRL B-23154T). On the
      basis of phenotypic and genetic data, B. sonorensis is most closely related to
      Bacillus licheniformis. B. sonorensis can be distinguished from B. licheniformis
      by salt tolerance, pigmentation, multilocus enzyme electrophoresis, reassociation
      of genomic DNA and sequence differences in protein-coding genes and 16S rRNA.

PMID- 11594595
TI  - Paenibacillus azoreducens sp. nov., a synthetic azo dye decolorizing bacterium
      from industrial wastewater.
AB  - An azo-dye-reducing, endospore-forming bacterium isolated from textile industry
      wastewater has been taxonomically studied. Particularly interesting was the
      ability of this organism to decolorize the azo dye Remazol Black B by 98% within
      24 h. Levels of 16S rRNA similarity between the isolate and Paenibacillus species
      ranged from 92.1 to 95.0%. The DNA G+C content was 46.8 mol % and anteiso
      branched C15:0 was the major fatty acid. Based upon the phenotypic properties and
      the phylogenetic inference, it is proposed that the bacterium should be
      designated Paenibacillus azoreducens sp. nov. The type strain of Paenibacillus
      azoreducens is CM1T (= DSM 13822T = NCIMB 13761T).

PMID- 11594596
TI  - Paenibacillus jamilae sp. nov., an exopolysaccharide-producing bacterium able to
      grow in olive-mill wastewater.
AB  - Endospore-forming strains were isolated from corn-compost treated with olive-mill
      wastewater ('alpechin'). The strains were taxonomically studied and proposed as a
      novel Paenibacillus species. These organisms (strains B.3T, B.7 and B.9) were
      particularly distinguishable from other aerobic spore-forming species by their
      ability to grow optimally in 100% (v/v) olive-mill wastewater at 30 degrees C and
      pH 7.0 and concomitant production of an interesting exopolysaccharide.
      Chemotaxonomic analysis revealed that MK-7 was the predominant menaquinone, the
      major fatty acid was anteiso C15:0 and the cell wall contained meso
      diaminopimelic acid. The DNA G+C content was 40.7 mol%. Comparative sequence
      analysis of 16S rDNA with different reference species from the genera Bacillus,
      Paenibacillus, Brevibacillus, Aneurinibacillus, Alicyclobacillus, Halobacillus,
      Virgibacillus, Amphibacillus, Coprobacillus and Gracilibacillus indicated that
      the isolated strains were highly related to the genus Paenibacillus. Strain B.3T
      formed an evolutionary lineage distinct from other species within the
      evolutionary radiation encompassing the genus Paenibacillus. Strain B.3T was a
      close relative of Paenibacillus polymyxa, but DNA-DNA relatedness data with this
      species was very low (relative binding ratio < 16%). Based on the morphological
      and physiological characteristics, as well as on the phylogenetic position
      determined by 16S rDNA analysis and DNA-DNA relatedness data, it is concluded
      that these strains should be designated a novel species, for which the name
      Paenibacillus jamilae sp. nov. is proposed. The type strain is B.3T (= CECT 5266T
      = DSM 13815T).

PMID- 11594597
TI  - Natrialba hulunbeirensis sp. nov. and Natrialba chahannaoensis sp. nov., novel
      haloalkaliphilic archaea from soda lakes in Inner Mongolia Autonomous Region,
      China.
AB  - Two haloalkaliphilic archaeal strains, X21T and C112T, were isolated from soda
      lakes in Inner Mongolia Autonomous Region, China. Their morphology, physiology,
      biochemical features, polar lipid composition and 16S rRNA genes were
      characterized in order to elucidate their taxonomy. According to these data,
      strains X21T and C112T belong to the genus Natrialba, although there are clear
      differences with respect to their physiology and polar lipid composition between
      the two strains and the type species, Natrialba asiatica. On the basis of low DNA
      DNA hybridizations, these two strains should be considered as new species of
      genus Natrialba. The names Natrialba hulunbeirensis sp. nov. (type strain X21T =
      AS 1.1986T = JCM 10989T) and Natrialba chahannaoensis sp. nov. (type strain C112T
      = AS 1.1977T = JCM 10990T) are proposed.

PMID- 11594598
TI  - Transfer of Pfennigia purpurea tindall 1999 (Amoebobacter purpureus Eichler and
      Pfennig 1988) to the genus Lamprocystis as Lamprocystis purpurea comb. nov.
AB  - On the basis of its close phylogenetic relationship to Lamprocystis
      roseopersicina, the phototrophic purple sulfur bacterium originally described as
      Amoebobacter purpureus and recently transferred to Pfennigia purpurea is
      reclassified as Lamprocystis purpurea comb. nov. In addition, an emended
      description of the genus Lamprocystis is given.

PMID- 11594599
TI  - Brevibacterium paucivorans sp. nov., from human clinical specimens.
AB  - Seven isolates from various human body sites displayed general chemotaxonomic and
      phenotypic characteristics of the genus Brevibacterium. This was corroborated by
      the 16S rRNA gene sequence analysis of strain CF62T, showing a sequence
      similarity of 99% to Brevibacterium mcbrellneri. However, DNA-DNA hybridization,
      a peculiar amino acid content of the cell wall and some phenotypic properties
      clearly suggested that these strains belong to a new species, for which the name
      Brevibacterium paucivorans sp. nov. is proposed. The type strain of B.
      paucivorans is CF62T (= DSM 13657T = LMG 19814T). The DNA G+C content of the type
      strain is 55.8 mol%.

PMID- 11594600
TI  - Polyhydroxyalkanoate-accumulating bacterium isolated from soil of a sugar-cane
      plantation in Brazil.
AB  - Strain IPT101T, isolated from the soil of a sugar-cane plantation in Brazil, was
      analysed in a polyphasic taxonomic study. The strain produces
      polyhydroxyalkanoates from sucrose and other carbon sources. Morphological,
      physiological and biochemical data as well as 16S rDNA, whole-cell protein and
      fatty acid analyses indicated that strain IPT101T represents a new species in the
      genus Burkholderia. The name Burkholderia sacchari sp. nov. is proposed, with
      strain IPT101T (= LMG 19450T = CCT 6771T) as the type strain.

PMID- 11594601
TI  - Mycobacterium frederiksbergense sp. nov., a novel polycyclic aromatic hydrocarbon
      degrading Mycobacterium species.
AB  - A polycyclic aromatic hydrocarbon-degrading bacterium isolated from coal tar
      contaminated soil in Denmark was characterized by a polyphasic approach.
      Phylogenetically and chemotaxonomically, it was related to members of the genus
      Mycobacterium. The isolate contains chemotaxonomic markers that are diagnostic
      for the genus Mycobacterium; i.e. the meso isomer of 2,6-diaminopimelic acid,
      arabinose and galactose as diagnostic whole-cell sugars, MK-9(H2) as the
      principal isoprenoid quinone, a mycolic acid pattern of alpha-mycolates,
      ketomycolates and wax-ester mycolates, unbranched saturated and unsaturated fatty
      acids plus a small amount of tuberculostearic acid and a significant amount of a
      C18:0 secondary alcohol. Based on the unique combination of chemical markers
      among mycobacteria, it is proposed that the isolate should be assigned to a new
      species, Mycobacterium frederiksbergense sp. nov. This novel species is
      phylogenetically closely related to Mycobacterium diernhoferi, Mycobacterium
      neoaurum and Mycobacterium hodleri. The type strain of M. frederiksbergense is
      strain FAn9T (= DSM 44346T = NRRL B-24126T).

PMID- 11594602
TI  - Corynebacterium freneyi sp. nov., alpha-glucosidase-positive strains related to
      Corynebacterium xerosis.
AB  - Three coryneform strains from clinical specimens were studied. They belonged to
      the genus Corynebacterium, since they had type IV cell walls containing
      corynemycolic acids. They had phenotypic characteristics that included alpha
      glucosidase, pyrazinamidase and alkaline phosphatase activities and fermentation
      of glucose, ribose, maltose and sucrose. These are the characteristics of
      Corynebacterium xerosis. Since this species is very rare in human pathology, the
      strains were studied in more detail by comparing the 16S-23S intergenic spacers,
      rDNA sequences and levels of DNA similarity of these three strains and those of
      the reference strains C. xerosis ATCC 373T and Corynebacterium amycolatum CIP
      103452T. According to DNA-DNA hybridization data, the three novel strains are
      members of the same species (level of DNA similarity >72%). Phylogenetic analysis
      revealed that these strains are closely related to C. xerosis and C. amycolatum,
      but DNA-relatedness experiments showed clearly that they constitute a distinct
      new species, with levels of DNA relatedness of less than 23% to C. xerosis ATCC
      373T and less than 5% to C. amycolatum CIP 103452T. Two other alpha-glucosidase
      positive strains presenting the same biochemical characteristics were included in
      the study and proved to be C. amycolatum. This new species can be differentiated
      from C. xerosis and C. amycolatum strains by carbon source utilization,
      intergenic spacer region length profiles and some biochemical characteristics
      such as glucose fermentation at 42 degrees C and growth at 20 degrees C. The name
      Corynebacterium freneyi sp. nov. is proposed with the type strain ISPB 6695110T
      (= CIP 106767T = DSM 44506T).

PMID- 11594603
TI  - Ralstonia taiwanensis sp. nov., isolated from root nodules of Mimosa species and
      sputum of a cystic fibrosis patient.
AB  - A polyphasic taxonomic study, including 16S rDNA sequence analysis, DNA-DNA
      hybridizations, DNA base ratio determinations, amplified 165 rDNA restriction
      analysis, whole-cell protein analyses and extensive biochemical characterization,
      was conducted to clarify the relationships of eight isolates from root nodules of
      Mimosa species and one isolate from sputum of a cystic fibrosis patient. All nine
      isolates were classified as a novel Ralstonia species, for which the name
      Ralstonia taiwanensis sp. nov. is proposed. The type strain is LMG 19424T (= CCUG
      44338T). R. taiwanensis effectively nodulated the Mimosa species and is the first
      beta-proteobacterium that is known to be capable of root nodule formation and
      nitrogen fixation.

PMID- 11594604
TI  - Enterococcus porcinus sp. nov. and Enterococcus ratti sp. nov., associated with
      enteric disorders in animals.
AB  - Recent insights have been brought to the taxonomy of the genus Enterococcus by
      studies applying whole-cell protein analysis and DNA-DNA reassociation
      experiments, in addition to conventional physiological tests. Using these
      techniques, a group of 10 strains resembling the physiological group III of
      enterococcal species was characterized. Five strains were recovered from pigs and
      five from rats with enteric disorders. On the basis of the results of
      conventional physiological tests, the most likely identity of these strains was
      Enterococcus durans or Enterococcus hirae. Analysis of the electrophoretic whole
      cell protein profiles showed two distinct clusters of virtually indistinguishable
      profiles: one composed of strains isolated from pigs, and one composed of strains
      isolated from rats. These protein profiles were not similar to the profiles of
      any previously described Enterococcus species. The results of DNA-DNA relatedness
      experiments were consistent with the results of the protein-profile analysis. The
      high levels of DNA relatedness found for pig isolates demonstrated that they
      belong to a new enterococcal species, for which the designation Enterococcus
      porcinus sp. nov. is proposed (type strain =DS 1390-83T =ATCC 700913T =CCUG
      43229T =NCIMB 13634T). Strains isolated from rats were found to comprise another
      new species, for which the designation Enterococcus ratti sp. nov. is proposed
      (type strain =DS 2705-87T =ATCC 700914T =CCUG 43228T =NCIMB 13635T). This report
      provides data on the phenotypic and genotypic characterization of these two new
      enterococcal species, which may represent diarrhoeagenic pathogens for animals.

PMID- 11594605
TI  - Globicatella sulfidifaciens sp. nov., isolated from purulent infections in
      domestic animals.
AB  - DNA-DNA hybridization experiments and comparative 165 rDNA sequence analysis
      revealed that six isolates from purulent joint and lung infections in calves,
      from a lung lesion in a sheep, and from a joint infection of a pig represented a
      novel species belonging to the genus Globicatella. Whole-cell protein
      electrophoresis and biochemical activity testing revealed that the isolates
      formed a homogeneous group differing from Globicatella sanguinis, the only
      species of this genus described to date. These animal isolates were classified as
      Globicatella sulfidifaciens sp. nov. with LMG 188441 (= CCUG 44365T), isolated
      from the lung of a calf, as the type strain. A detailed description of its
      phenotypic characteristics is presented. Hydrogen sulphide production was found
      to be a very useful diagnostic feature.

PMID- 11594606
TI  - Mycobacterium immunogenum sp. nov., a novel species related to Mycobacterium
      abscessus and associated with clinical disease, pseudo-outbreaks and contaminated
      metalworking fluids: an international cooperative study on mycobacterial
      taxonomy.
AB  - PCR-restriction enzyme pattern analysis of a 439 bp hsp65 gene segment identified
      113 unique isolates among non-pigmented rapidly growing mycobacteria (RGM) from
      clinical and environmental sources that failed to match currently recognized
      species patterns. This group represented 40% of isolates recovered from
      bronchoscope contamination pseudo-outbreaks, 0% of disease-associated nosocomial
      outbreaks and 4% of routine clinical isolates of the Mycobacterium
      abscessus/Mycobacterium chelonae group submitted to the Mycobacteria/Nocardia
      laboratory for identification. It is grouped within the Mycobacterium fortuitum
      complex, with growth in less than 7 d, absence of pigmentation, positive 3-d
      arylsulfatase reaction and growth on MacConkey agar without crystal violet. It
      exhibited overlapping biochemical, antimicrobial susceptibility and HPLC
      characteristics of M. abscessus and M. chelonae. By 16S rRNA gene sequencing,
      these isolates comprised a homogeneous group with a unique hypervariable region A
      sequence and differed by 8 and 10 bp, respectively, from M. abscessus and M.
      chelonae. Surprisingly, this taxon contained two copies of the ribosomal operon,
      compared with single copies in the two related species. By DNA-DNA hybridization,
      this new group exhibited <30% homology with recognized RGM species. The name
      Mycobacterium immunogenum sp. nov. is proposed for this new taxon.

PMID- 11594607
TI  - Description of two novel species of the genus Kitasatospora Omura et al. 1982,
      Kitasatospora cineracea sp. nov. and Kitasatospora niigatensis sp. nov.
AB  - Five actinomycete strains, SK-3255T, SK-3406T, SK-3412, SK-3421 and OM-5023, were
      isolated using a novobiocin-containing agar medium from soil samples. These
      strains produced long spore chains on aerial mycelium and contained LL- and meso
      diaminopimelic acids (DAPs) in the cell wall. On the basis of morphological and
      chemotaxonomic characteristics and phylogenetic analysis, these five strains were
      classified into the genus Kitasatospora. DNA-DNA hybridization and comparison of
      physiological characteristics revealed that strains SK-3255T and SK-3406T
      differed from known species. Strains SK-3406T, SK-3412 and SK-3421 were regarded
      as the same species. Strain OM-5023 was identified as Kitasatospora griseola.
      Therefore, two novel species are proposed, Kitasatospora cineracea sp. nov. and
      Kitasatospora niigatensis sp. nov., with the type strains K. cineracea SK-3255T
      (= IFO 16452T = JCM 10915T = NRRL B-23134T) and K. niigatensis SK-3406T (= IFO
      16453T = JCM 10916T = NRRL B-24135T).

PMID- 11594608
TI  - Classification of metal-resistant bacteria from industrial biotopes as Ralstonia
      campinensis sp. nov., Ralstonia metallidurans sp. nov. and Ralstonia basilensis
      Steinle et al. 1998 emend.
AB  - Thirty-one heavy-metal-resistant bacteria isolated from industrial biotopes were
      subjected to polyphasic characterization, including 16S rDNA sequence analysis,
      DNA-DNA hybridizations, biochemical tests, whole-cell protein and fatty-acid
      analyses. All strains were shown to belong to the Ralstonia branch of the beta
      Proteobacteria. Whole-cell protein profiles and DNA-DNA hybridizations revealed
      two clearly distinct groups, showing low similarity to known Ralstonia species.
      These two groups, of 8 and 17 isolates, were assigned to two new species, for
      which the names Ralstonia campinensis sp. nov. and Ralstonia metallidurans sp.
      nov. are proposed. The type strains are WS2T (= LMG 19282T = CCUG 44526T) and
      CH34T (= LMG 1195T = DSM 2839T), respectively. Six isolates were allocated to
      Ralstonia basilensis, which presently contains only the type strain; an
      emendation of the latter species description is therefore proposed.

PMID- 11594609
TI  - Nocardia beijingensis sp. nov., a novel isolate from soil.
AB  - The taxonomic status of a soil isolate, provisionally assigned to the genus
      Nocardia, was established following a polyphasic study. An almost complete
      sequence of the 16S rDNA of the strain was determined and aligned with available
      sequences for nocardiae and phylogenetic trees were inferred using four tree
      making algorithms. The organism was associated consistently with the type strains
      of Nocardia brasiliensis and Nocardia farcinica in the neighbour-joining
      analysis, albeit with low bootstrap values. It was also found to have
      chemotaxonomic and morphological properties consistent with its assignment to the
      genus Nocardia. The organism was readily separated from representatives of other
      Nocardia species by a broad range of phenotypic properties. The name proposed for
      the novel species is Nocardia beijingensis sp. nov. The type strain is AS4.1521T
      (= IFO 16342T = JCM 10666T).

PMID- 11594610
TI  - Caloranaerobacter azorensis gen. nov., sp. nov., an anaerobic thermophilic
      bacterium isolated from a deep-sea hydrothermal vent.
AB  - A thermophilic, anaerobic, chemo-organotrophic bacterium, designated MV1087T, was
      isolated from a deep-sea hydrothermal chimney sample collected from the Mid
      Atlantic Ridge. The cells were straight, motile and stained gram-negative. Growth
      was observed from 45 to 65 degrees C, with an optimum around 65 degrees C. No
      growth was observed at 40 or 70 degrees C. Growth was observed from pH 5.5 to 9.0
      and the optimum pH was around 7. The salinity range for growth was 10-100 g sea
      salt l(-1) (corresponding to 6.5-65 g NaCl l(-1)) with an optimum at 30 g sea
      salt l(-1) (20 g NaCl l(-1)). Strain MV1087T was heterotrophic, able to ferment
      proteinaceous substrates, such as brain/heart infusion and gluten, and
      carbohydrates, such as glucose, xylan and starch. The DNA G+C content was 27
      mol%. Phylogenetic analyses using 16S rDNA sequences indicated that strain
      MV1087T belonged to cluster XII of the Clostridium subphylum. Due to its
      phenotypic and genotypic characteristics, isolate MV1087T is proposed as a novel
      species of a new genus, Caloranaerobacter azorensis gen. nov., sp. nov. The type
      strain is MV1087T (= CNCM I-2543T = DSM 13643T).

PMID- 11594611
TI  - Characterization of novel human oral isolates and cloned 16S rDNA sequences that
      fall in the family Coriobacteriaceae: description of olsenella gen. nov.,
      reclassification of Lactobacillus uli as Olsenella uli comb. nov. and description
      of Olsenella profusa sp. nov.
AB  - The diversity of organisms present in the subgingival pockets of patients with
      periodontitis and acute necrotizing ulcerative gingivitis (ANUG) were examined
      previously. The 16S rRNA genes of subgingival plaque bacteria were amplified
      using PCR with a universal forward primer and a spirochaete-selective reverse
      primer. The amplified DNA was cloned into Escherichia coli. In one subject with
      ANUG, 70 clones were sequenced. Seventy-five per cent of the clones were
      spirochaetal, as expected. Twelve of the remaining clones fell into two clusters
      that represent novel phylotypes in the family Coriobacteriaceae. The first novel
      phylotype was most closely related to Atopobium rimae (98% similarity). The
      phylotype probably represents a novel Atopobium species, but will not be named
      until cultivable strains are obtained. The second novel phylotype was only 91%
      similar to described Atopobium species and 84% similar to Coriobacterium
      glomerans. The 16S rRNA sequences of the type strain of Lactobacillus uli and a
      strain representing the Moores' Eubacterium group D52 were determined as part of
      on ongoing sequence analysis of oral bacteria. The sequence for L. uli was more
      than 99.8% similar to sequences for the second clone phylotype. It therefore
      appears that the second clone phylotype and L. uli represent the same species.
      The sequence for the Eubacterium D52 strain was 95.6% similar to that of L. uli.
      The G+C content of the DNA of L. uli and Eubacterium D52 is 63-64 mol %. These
      organisms are thus distinct from the neighbouring genus Atopobium, which has a
      DNA G+C content of 35-46 mol%. A new genus, Olsenella gen. nov., is proposed for
      these two species on the basis of phenotypic characteristics and 16S rRNA
      sequence analysis to include Olsenella uli comb. nov. and Olsenella profusa sp.
      nov.

PMID- 11594612
TI  - Geobacter bremensis sp. nov. and Geobacter pelophilus sp. nov., two dissimilatory
      ferric-iron-reducing bacteria.
AB  - Two strictly anaerobic, dissimilatory ferric-iron-reducing bacteria, strains
      Dfr1T and Dfr2T, were isolated from freshwater mud samples with ferrihydrite as
      electron acceptor. Both strains also grew by reducing Mn(IV), S0 and fumarate.
      Electron donors used by strains Dfr1T and Dfr2T for growth with ferric iron as
      electron acceptor included hydrogen, formate, acetate, pyruvate, succinate,
      fumarate and ethanol. An affiliation with the family Geobacteraceae was revealed
      by comparative analysis of 165 rRNA gene sequences. Strains Dfr1T and Dfr2T
      shared 92.5% sequence identity and their closest known relative was Geobacter
      sulfurreducens, with approximately 93% sequence identity. Cultures and colonies
      of strains Dfr1T and Dfr2T were intensely red in colour, due to the presence of c
      type cytochromes. On the basis of physiological and phylogenetic data, strain
      Dfr1T (= DSM 12179T = OCM 796T) is described as Geobacter bremensis sp. nov. and
      strain Dfr2T (= DSM 12255T = OCM 797T) as Geobacter pelophilus sp. nov.

PMID- 11594613
TI  - A new genus of the order Actinomycetales, Virgosporangium gen. nov., with
      descriptions of Virgosporangium ochraceum sp. nov. and Virgosporangium
      aurantiacum sp. nov.
AB  - Four motile spored strains were isolated from soil samples collected in Japan.
      The cultures formed long, narrow sporangia on short sporangiophores directly on
      the substrate mycelium. The sporangia develop singly or in clusters above the
      surface of the substrate. Each sporangium contains a single row of six or more
      motile spores. Glutamic acid, glucosamine, glycine, alanine and 3-OH
      diaminopimelic acid are present in the cell wall; the whole-cell sugars are 3-O
      methylmannose, rhamnose, mannose, arabinose, galactose, xylose and glucose; and
      the predominant menaquinones are 10(H4), 10(H6) and 10(H8). The diagnostic
      phospholipid is phosphatidylethanolamine. The acyl type of the muramic acid is
      glycolyl. The G+C content is 71 mol%. Mycolic acids are absent. The
      chemotaxonomic data indicate that these strains belong to the family
      Micromonosporaceae. Analysis of 165 rDNA sequences suggested that these organisms
      fall into a distinct clade within the family Micromonosporaceae for which a new
      genus, Virgosporangium gen. nov., is proposed containing the species
      Virgosporangium ochraceum sp. nov. (strains YU655-43T, YU793-41 and YU794-41) and
      Virgosporangium aurantiacum sp. nov. (strain YU438-5T).

PMID- 11594614
TI  - Borrelia sinica sp. nov., a lyme disease-related Borrelia species isolated in
      China.
AB  - A survey was performed for Lyme disease borrelia in the southern part of China,
      in Zhejiang, Sichuan and Anhui provinces, along the Yangtze River valley, in May
      of 1997 and 1998. Twenty isolates from Ixodes granulatus, Ixodes ovatus, Apodemus
      agrarius and Niviventer confucianus were obtained. These isolates were
      characterized by RFLP of the 5S-23S rDNA intergenic spacer, sequence analysis of
      the intergenic spacer, 16S rDNA and flagellin gene, DNA-DNA hybridization
      analysis, SDS-PAGE and Western blotting with mAbs. Six isolates from A. agrarius,
      five from I. granulatus collected in Zhejiang province and one from N.
      confucianus in Sichuan province were highly similar to strains 10MT and 5MT
      isolated in Korea and classified as Borrelia valaisiana. Four isolates from A.
      agrarius and I. granulatus collected in Zhejiang province generated unique RFLP
      patterns and phylogenetic analysis of the 16S rDNA and flagellin gene sequences
      suggested that the isolates should be classified as B. valaisiana. Furthermore,
      three isolates (CMN1a, CNM2, CMN3T) from N. confucianus captured in Sichuan
      province and one (CWO1) from I. ovatus in Anhui province showed lower 165 rDNA
      sequence similarity (less than 99.0%) to sequences of previously described Lyme
      disease-related Borrelia species. DNA-DNA hybridization results revealed that
      strains CMN3T and CMN1a were clearly distinct from all other known Lyme disease
      Borrelia species. Electron microscope observation showed the spirochaetes to be
      morphologically similar to those of Borrelia, but the cells contained only four
      periplasmic flagella inserted at each end of the spirochaetes. Based on these
      results, a new Borrelia species, Borrelia sinica sp. nov., is proposed. Strain
      CMN3T is the type strain of this new species.

PMID- 11594615
TI  - Natronobacterium nitratireducens sp. nov., a aloalkaliphilic archaeon isolated
      from a soda lake in China.
AB  - Two novel haloalkaliphilic archaea, strains C231T and C42, were isolated from a
      soda lake in China. Cells of the two strains were rod-shaped and gram-negative
      and colonies were bright red. They required at least 2.5 M NaCl for growth, with
      an optimum at 3.5 M NaCl, and grew over a pH range from 8.0 to 10.5, with an
      optimum at pH 8.5. Hypotonic treatment with less than 1.5 M NaCl caused cell
      lysis. They had similar polar lipid compositions, possessing the diphytanyl
      (C20:C20) and phytanyl-sesterterpanyl (C20:C25) diether derivatives of
      phosphatidylglycerol and phosphatidylglycerophosphate methyl ester and a minor
      phospholipid, PL1. No glycolipids were detected. Comparison of 16S rDNA sequences
      and morphological features placed them in the genus Natronobacterium. Detailed
      phenotypic characterization and DNA-DNA hybridization studies revealed that the
      two strains belong to a new species in the genus Natronobacterium, for which the
      name Natronobacterium nitratireducens sp. nov. is proposed. The type strain is
      C231T (= AS 1.1980T = JCM 10879T).

PMID- 11594616
TI  - Xenophilus azovorans gen. nov., sp. nov., a soil bacterium that is able to
      degrade azo dyes of the Orange II type.
AB  - The taxonomy of strain KF46FT, which was isolated previously after an aerobic
      enrichment with the azo compound 1-(4'-carboxyphenylazo)-2-naphthol as the sole
      source of energy and carbon, was investigated by a polyphasic approach. The
      organism contained a quinone system with ubiquinone Q-8 and 2-hydroxyputrescine
      and putrescine as the major polyamines, suggesting that strain KF46FT belonged to
      the beta-subclass of the Proteobacteria. The polar lipid profile consisted mainly
      of phosphatidylethanolamine and minor amounts of phosphatidylglycerol and
      diphosphatidylglycerol. Sequencing of the 16S rRNA gene supported its placement
      in the family Comamonadaceae, but the sequence similarities to the most closely
      related species of the genera Hydrogenophaga, Acidovorax, Comamonas and
      Xylophilus were only in the range 95.0 to 96.1%. Different methods for the
      construction of phylogenetic trees showed the separate position of strain KF46FT
      'between' the genera Hydrogenophaga, Variovorax, Comamonas and Xylophilus.
      Analysis of the fatty acids revealed an unusual profile, with the presence of 8:0
      3-OH, 10:0 3-OH, 16:1 2-OH, 16:0 2-OH and 18:1 2-OH in addition to 17:0 cyclo,
      which is unique among the previously described genera of the family
      Comamonadaceae. Thus, a new taxon is proposed for strain KF46FT, with the name
      Xenophilus azovorans gen. nov., sp. nov.

PMID- 11594618
TI  - Hydrogenothermus marinus gen. nov., sp. nov., a novel thermophilic hydrogen
      oxidizing bacterium, recognition of Calderobacterium hydrogenophilum as a member
      of the genus Hydrogenobacter and proposal of the reclassification of
      Hydrogenobacter acidophilus as Hydrogenobaculum acidophilum gen. nov., comb.
      nov., in the phylum 'Hydrogenobacter/Aquifex'.
AB  - A novel thermophilic, hydrogen-oxidizing bacterium, VM1T, has been isolated from
      a marine hydrothermal area of Vulcano Island, Italy. Cells of the strain were
      gram-negative rods, 2-4 microm long and 1-1.5 microm wide with four to seven
      monopolarly inserted flagella. Cells grew chemolithoautotrophically under an
      atmosphere of H2/CO2 (80:20) in the presence of low concentrations of O2 (optimum
      1-2%). Carbohydrates and peptide substrates were not utilized, neither for energy
      generation nor as a source of cellular carbon. Growth of VM1T occurred between 45
      and 80 degrees C with an optimum at 65 degrees C. Growth was observed between pH
      5 and 7. NaCl stimulated growth in the range 0.5-6% with an optimum at 2-3%.
      Hydrogen could not be replaced by elemental sulfur or thiosulfate as electron
      donors. Nitrate and sulfate were not used as electron acceptors. The major
      respiratory lipoquinone was a new menathioquinone. Analysis of the fatty acids of
      VM1T revealed straight-chain saturated C18:0 and the unsaturated C18:1omega9c and
      C20:1omega9c as major components. The G+C content of the total DNA was 43 mol%.
      Phylogenetic analysis placed strain VM1T near the members of the genera
      Hydrogenobacter, Thermocrinis and Aquifex on a separate deep-branching
      phylogenetic lineage. Therefore, it is proposed that strain VM1T (= DSM 12046T =
      JCM 10974T) represents a novel species within a new genus, for which the name
      Hydrogenothermus marinus gen. nov., sp. nov., is proposed. In addition, it is
      shown that Calderobacterium hydrogenophilum should be transferred to the genus
      Hydrogenobacter; the name Hydrogenobacter hydrogenophilus comb. nov. (DSM 2913T =
      JCM 8158T) is proposed for this organism. Furthermore, on the basis of 16S rRNA
      sequence analysis, Hydrogenobacter acidophilus is only distantly related to
      Hydrogenobacter species. Owing to this finding and its growth at low pH, the name
      Hydrogenobaculum acidophilum gen. nov., comb. nov., is proposed for
      Hydrogenobacter acidophilus. The type strain is JCM 8795T (= DSM 11251T).

PMID- 11594617
TI  - Form species Nostoc commune (Cyanobacteria).
AB  - The form species concept for the Cyanobacteria was evaluated using a
      comprehensive set of Nostoc samples that were collected during the past two
      centuries, from all continents, including regions from the Tropics to the Poles.
      Phylogenies were constructed based upon the conserved regions of tRNALeu (UAA)
      group I intron DNA sequences. Thirty-four forms contained a tRNALeu (UAA) intron
      of 284 nt. These 284-nt introns contained 200 nt of conserved sequence that, in
      most cases, shared 100% sequence identity, they had three variable regions (I, II
      and III) amounting to 84 nt, contained no hypervariable region and formed a
      discrete cluster in phylogenetic analysis. These forms represented 31 independent
      populations in both hemispheres and constitute examples of form species Nostoc
      commune. Multiple introns were obtained from several of the populations. Ten
      populations contained introns of 287-340 nt with a hypervariable region, 8 to 59
      nt in length, located between variable regions I and II. Alignments identified 15
      examples where 5'-AAAAUCC-3' occurred at the hypervariable region-variable region
      II boundary; this sequence is identical to the conserved sequence at the 3'
      intron-exon boundary (splice site) within the tRNALeu (UAA) gene. The possibility
      that hypervariable regions were removed from the primary intron through secondary
      splicing was tested in vitro but proved to be negative under the experimental
      conditions used. Shared morphologies of genetically different strains, dissimilar
      morphologies in strains that share identical genetic markers, incorrect naming of
      culture collection strains and genetic drift in cultured strains emphasize that
      the successful delineation of cyanobacterial species requires the application of
      multiple taxonomic criteria.

PMID- 11594619
TI  - Transfer of Rhodopseudomonas acidophila to the new genus Rhodoblastus as
      Rhodoblastus acidophilus gen. nov., comb. nov.
AB  - Rhodopseudomonas acidophila has unique properties among the phototrophic alpha
      Proteobacteria and is quite distinct from the type species of Rhodopseudomonas,
      Rhodopseudomonas palustris. Therefore, the transfer of Rhodopseudomonas
      acidophila to Rhodoblastus acidophilus gen. nov., comb. nov., is proposed. This
      proposal is in accordance with other taxonomic reclassifications proposed
      previously and fully reflects the phylogenetic distance from Rhodopseudomonas
      palustris.

PMID- 11594620
TI  - Pigmentiphaga kullae gen. nov., sp. nov., a novel member of the family
      Alcaligenaceae with the ability to decolorize azo dyes aerobically.
AB  - The taxonomic position of Pseudomonas strain K24, which was isolated previously
      after an aerobic enrichment with the azo compound 1-(4'-carboxyphenylazo)-4
      naphthol as the sole source of carbon and energy, was investigated. The detection
      of a quinone system with ubiquinone Q-8 as the predominant compound and a
      polyamine pattern with putrescine and 2-hydroxyputrescine as the major polyamines
      present suggested that strain K24T belongs to the beta-subclass of the
      Proteobacteria. This was supported by sequencing the 16S rRNA gene, which
      demonstrated about 95-96% sequence similarity to different species of the genera
      Achromobacter, Alcaligenes and Bordetella. This suggested that strain K24T is a
      member of the family Alcaligenaceae. The G+C content of the DNA was 68.5 mol %.
      Different methods for the construction of phylogenetic dendrograms placed strain
      K24T separate from the genera Alcaligenes, Achromobacter and Bordetella. Analysis
      of the fatty acids demonstrated the presence of 10:0 3-OH and high concentrations
      of summed feature 7 (18:1omega7c, 18:1omega9t and/or 18:1omega12t) and 19:0
      cycloomega8c, which is unique among previously described species of the genera
      Alcaligenes, Achromobacter and Bordetella. On the basis of the low 16S rRNA
      sequence similarities, the composition of the fatty acid profile and unique
      phenotypic properties, a new genus and species is proposed for strain K24T with
      the name Pigmentiphaga kullae gen. nov., sp. nov.

PMID- 11594621
TI  - Methanofollis aquaemaris sp. nov., a methanogen isolated from an aquaculture fish
      pond.
AB  - A novel methanogen, designated strain N2F9704T, was isolated from an aquaculture
      fish pond near Wang-gong, Taiwan. The cells were irregular cocci, non-motile, 1.2
      2.0 microm in diameter and stained gram-negative. Cells of strain N2F9704T lysed
      easily by SDS treatment (0.1 g l(-1)) and the S-layer protein had an Mr of
      137000. The catabolic substrates used included formate and H2+CO2, but not
      acetate, methanol, trimethylamine or secondary alcohols. The optimal growth
      parameters for strain N2F9704T were pH 6.5, 37 degrees C with 0.5% NaCl. Trace
      amounts of tungstate not only promoted growth but also extended the range of
      growth conditions. Analysis of the 16S rDNA sequence revealed a phylogenetic
      relationship to Methanofollis species and the name Methanofollis aquaemaris sp.
      nov. is therefore proposed for strain N2F9704T (= OCM 746T = CCRC 16166T).
      Additionally, the strain was infected with a novel coccus-shaped, enveloped virus
      with a diameter of 200 nm.

PMID- 11594622
TI  - Helicobacter ganmani sp. nov., a urease-negative anaerobe isolated from the
      intestines of laboratory mice.
AB  - Spiral bacteria were isolated from the intestines of laboratory mice during a
      study examining the presence of Helicobacter species and other spiral organisms
      naturally infecting mice maintained at four different animal facilities in
      Sydney, Australia. One group of 17 isolates, cultured from mice from three of the
      four facilities, were found to be helicobacters but did not fall within any of
      the 18 currently recognized species. These isolates were unusual in that they
      only grew anaerobically at 37 degrees C and were incapable of growth under
      microaerobic conditions. Like Helicobacter rodentium, isolates possessed single,
      bipolar, unsheathed flagella and were urease-negative. They were positive for
      oxidase and reduced nitrate to nitrite but did not hydrolyse hippurate or indoxyl
      acetate, grew on charcoal agar and were resistant to cephalothin. 16S rDNA
      sequences from four strains were determined and found to be identical to one
      another. H. rodentium was the most closely related species in terms of 16S rDNA
      sequence similarity (98.2%). Numerical analysis of whole-cell proteins by SDS
      PAGE for nine isolates was carried out with a comparison to all known
      Helicobacter species, including newly determined profiles from three H. rodentium
      strains. The new isolates were clearly differentiated from H. rodentium and other
      Helicobacter spp. On the basis of this data, including genetic, biochemical and
      protein analysis, it is proposed that these isolates belong to Helicobacter
      ganmani sp. nov. (type strain CMRI H02T = CCUG 43526T = CIP 106846T).

PMID- 11594623
TI  - Acinetobacter ursingii sp. nov. and Acinetobacter schindleri sp. nov., isolated
      from human clinical specimens.
AB  - The taxonomic status of two recently described phenetically distinctive groups
      within the genus Acinetobacter, designated phenon 1 and phenon 2, was
      investigated further. The study collection included 51 strains, mainly of
      clinical origin, from different European countries with properties of either
      phenon 1 (29 strains) or phenon 2 (22 strains). DNA-DNA hybridization studies and
      DNA polymorphism analysis by AFLP revealed that these phenons represented two new
      genomic species. Furthermore, 16S rRNA gene sequence analysis of three
      representatives of each phenon showed that they formed two distinct lineages
      within the genus Acinetobacter. The two phenons could be distinguished from each
      other and from all hitherto-described Acinetobacter (genomic) species by specific
      phenotypic features and amplified rDNA restriction analysis patterns. The names
      Acinetobacter ursingii sp. nov. (type strain LUH 3792T = NIPH 137T = LMG 19575T =
      CNCTC 6735T) and Acinetobacter schindleri sp. nov. (type strain LUH 5832T = NIPH
      1034T = LMG 19576T = CNCTC 6736T) are proposed for phenon 1 and phenon 2,
      respectively. Clinical and epidemiological data indicate that A. ursingii has the
      capacity to cause bloodstream infections in hospitalized patients.

PMID- 11594624
TI  - Thermotoga petrophila sp. nov. and Thermotoga naphthophila sp. nov., two
      hyperthermophilic bacteria from the Kubiki oil reservoir in Niigata, Japan.
AB  - Two hyperthermophilic bacteria, strains RKU-1T and RKU-10T, which grew optimally
      at 80 degrees C, were isolated from the production fluid of the Kubiki oil
      reservoir in Niigata, Japan. They were strictly anaerobic, rod-shaped
      fermentative heterotrophs. Based on the presence of an outer sheath-like
      structure (toga) and 16S rDNA sequences, they were shown to belong to the genus
      Thermotoga. Cells of strain RKU-1T were 2-7 microm by 0.7-1.0 microm, with
      flagella. They grew at 47-88 degrees C on yeast extract, peptone, glucose,
      fructose, ribose, arabinose, sucrose, lactose, maltose, starch and cellulose as
      sole carbon sources. Cells of strain RKU-10T were 2-7 microm by 0.8-1.2 microm,
      with flagella. They grew at 48-86 degrees C on yeast extract, peptone, glucose,
      galactose, fructose, mannitol, ribose, arabinose, sucrose, lactose, maltose and
      starch as sole carbon sources. While strains RKU-1T and RKU-10T reduced elemental
      sulfur to hydrogen sulfide, their final cell yields and specific growth rates
      decreased in the presence of elemental sulfur. Thiosulfate also inhibited growth
      of strain RKU-1T but not strain RKU-10T. The G+C contents of the DNA from strains
      RKU-1T and RKU-10T were 46.8 and 46.1 mol%. Phenotypic characteristics and 165
      rDNA sequences of the isolates were similar to those of Thermotoga maritima and
      Thermotoga neapolitana, both being hyperthermophilic bacteria isolated from
      hydrothermal fields. However, the isolates differed from these species in their
      minimum growth temperatures, utilization of some sugars, sensitivity to
      rifampicin and the effects of elemental sulfur and thiosulfate on growth. The low
      levels (less than 31%) of DNA reassociation between any two of these
      hyperthermophilic Thermotoga strains indicated that the isolates were novel
      species. Analysis of the gyrB gene sequences supported the view that the isolates
      were genotypically different from these reference species. The isolates were
      named Thermotoga petrophila sp. nov., with type strain RKU-1T (= DSM 13995T = JCM
      10881T), and Thermotoga naphthophila sp. nov., with type strain RKU-10T (= DSM
      13996T = JCM 10882T).

PMID- 11594625
TI  - Desulforegula conservatrix gen. nov., sp. nov., a long-chain fatty acid
      oxidizing, sulfate-reducing bacterium isolated from sediments of a freshwater
      lake.
AB  - A novel sulfate-reducing bacterium, strain Mb1PaT, was isolated from the
      sediments of a freshwater floodplain lake. Cells of strain Mb1PaT were rod
      shaped, 1-1.3 microm wide and 2.6-3 microm long, motile and Gram-negative. The
      bacterium grew on straight-chain carboxylic acids with 4-17 carbon atoms.
      Electron donors with an even number of carbon atoms were oxidized to acetate and
      electron donors with an odd number of carbon atoms were oxidized to acetate and
      propionate. No other compounds were found to be used as electron donors. No
      growth occurred in the absence of sulfate. The optimum temperature for growth was
      between 25 and 30 degrees C and the maximum temperature for growth was 32 degrees
      C. Strain Mb1PaT grew very slowly in medium with 5 g NaCl l(-1) with optimum
      growth occurring with up to 1.0 g NaCl l(-1). Analysis of the 16S rRNA gene
      showed that strain Mb1PaT belonged to the delta-subclass of the Proteobacteria,
      was a member of the family Desulfobacteraceae, but lacked similarity with any
      currently described representatives. The combined phylogenetic analysis and
      physiological data indicate that strain Mb1PaT represents a new genus and the
      name Desulforegula conservatrix is proposed. The type strain is Mb1PaT (= DSM
      13527T = ATCC BAA-134T).

PMID- 11594626
TI  - Phylogenetic analysis of the psychrophobic yeast Arxiozyma telluris and the
      reinstatement of Candida pintolopesii (van Uden) Meyer et Yarrow and Candida
      slooffii van Uden et do Carmo Sousa.
AB  - A phylogenetic analysis was conducted upon ten strains of the psychrophobic yeast
      species Arxiozyma telluris using nuclear rDNA (18S and 26S) and mitochondrial
      cytochrome-c oxidase subunit II (COX2) gene sequences. Strains examined included
      those described originally as Candida slooffii, Torulopsis bovina (= Candida
      bovina) and Torulopsis pintolopesii (= Candida pintolopesii), which are all
      currently accepted as synonyms of Arxiozyma telluris. Comparative 18S rDNA
      sequence analysis showed that these strains formed a genealogically highly
      related group, which was phylogenetically distinct from any other ascomycetous
      species studied. The results showed that A. telluris, as currently described,
      appears to be composed of a complex of closely related but nevertheless separate
      taxa. rDNA and COX2 gene sequence data revealed that CBS 1787T, the type strain
      of C. pintolopesii, the currently recognized asexual form (anamorph) of A.
      telluris, along with strains CBS 2676 and CBS 2985 formed a distinct taxon that
      is phylogenetically separate from A. telluris. Similarly, the sequence data also
      showed that C. slooffii is a distinct taxon and support the reinstatement of this
      species. However, with regard to the relationship between the type strains of A.
      telluris (CBS 2685T) and C bovina (CBS 2760T), discrepancies were observed
      between the rDNA and COX2 sequence datasets, and these results are discussed in
      more detail.

PMID- 11594628
TI  - Corrigenda to the validation lists.
AB  - Some repetitions, omissions or errors have been made in the Validation Lists
      published in the International Journal of Systematic Bacteriology and they are
      corrected in this paper.

PMID- 11594627
TI  - Metschnikowia koreensis sp. nov., a novel yeast species isolated from flowers in
      Korea.
AB  - A novel ascomycetous yeast was isolated from flowers of Lilium sp. and Ipomoea
      sp. in Korea. The name Metschnikowia koreensis sp. nov. (type strain SG99-34T =
      CBS 8854T = KCTC 7998T) is proposed for this novel species based on comparative
      sequence analyses of the D1/D2 domain of 26S rDNA and phenotypic characteristics.

PMID- 11594629
TI  - Nomenclature of the subgenera Moraxella and Branhamella and of the nine species
      included in these subgenera and proposal to modify rule 34a of the
      Bacteriological Code (1990 Revision). Request for an opinion.
AB  - The subgenera Moraxella and Branhamella and the nine species included in these
      subgenera were inadvertently omitted from the Approved Lists of Bacterial Names
      and have never been revived according to Rule 28a of the Bacteriological Code
      (1990 Revision). The author requests that these names be revived and considered
      to be validly published in the 'Index of the bacterial and yeast nomenclatural
      changes published in the International Journal of Systematic Bacteriology since
      the 1980 Approved Lists of Bacterial Names (1 January 1980 to 1 January 1985)',
      which appears in the July 1985 issue of the International Journal of Systematic
      Bacteriology. Another problem is the status of the species included in the
      subgenera Moraxella and Branhamella because the Bacteriological Code (1990
      Revision) does not envisage the status of a species transferred into a subgenus.
      The same is true for a species transferred into a subspecies. The author requests
      that such species be considered as new combinations and, according to this,
      proposes to modify Rule 34a of the Bacteriological Code (1990 Revision).

PMID- 11594630
TI  - Hydrogenated fish fat for grazing dairy cows in summer.
AB  - Thirty-two multiparous Holando argentino cows in mid lactation were randomly
      assigned to two treatments: control or HFF (hydrogenated fish fat) at Rafaela, 31
      degrees 11' South, during summer 1997/1998, to evaluate the effect of using HFF
      as a supplement under grazing conditions. Animals in both treatments grazed an
      alfalfa pasture, and were confined from 1000 hours to 1700 hours daily in a
      shaded pen where water was provided ad libitum. During each milking, animals in
      the control group received 3.73 kg dry matter per cow each day (DM cow(-1) day(
      1)) concentrate (15% crude protein; 8.69 MJ energy for location/kg DM). Cows in
      the HFF group received 3.25 kg DM cow(-1) day(-1) concentrate, plus 0.200 kg DM
      cow(-1) day(-1) HFF. Both diets presented similar energy, protein and neutral
      detergent fibre contents. The trial was performed during a strong "El Nino"
      event, which resulted in a total rainfall of 396.3 mm (80% higher than normal).
      The mean temperature was 23.7 (SD 3.2) degrees C and the mean temperature
      humidity index was 72.9 (SD 4.96). Production data were analysed using a
      completely randomised design with analysis of covariance. Supplementation with
      HFF produced an increase in daily milk production (26.4 (SD 2.46) l/cow compared
      to 23.9 (SD 2.68) l/cow for the controls; P<0.05). Milk fat production was higher
      for HFF (P<0.05): 941 (SD 96) g cow(-1) day(-1) as compared to controls, which
      yielded 846 (SD 95) g cow(-1) day(-1). Milk protein yields also differed
      significantly (P<0.05), the respective values for HFF and controls being 795 (SD
      72) g cow(-1) day(-1) and 715 (SD 83) g cow(-1) day(-1). It was concluded that
      hydrogenated fish fat could be a good ingredient to sustain high yields and
      elevated maintenance requirements in a grazing system during hot conditions.

PMID- 11594631
TI  - Natural very-low-frequency sferics and headache.
AB  - Very-low-frequency (VLF) atmospherics or sferics are pulse-shaped alternating
      electric and magnetic fields which originate from atmospheric discharges
      (lightning). The objective of the study was threefold: (i) to analyse numerous
      parameters characterizing the sferics activity with regard to their suitability
      for field studies, (ii) to identify meteorological processes related to the
      sferics activity and (iii) to investigate the possible association of sferics
      with pain processes in patients suffering from migraine- and tension-type
      headaches. Over a period of 6 months (July through December) the sferics activity
      in the area of Giessen (Germany) was recorded. Three sferics parameters were
      chosen. The number of sferics impulses per day, the variability of the impulse
      rate during a day and the variability in comparison to the preceding day were
      correlated with weather processes (thunderstorm, temperature, vapour pressure,
      barometric pressure, humidity, wind velocity, warm sector). Significant
      correlations were obtained during the summer months (July, August) but not during
      the autumn months (October, November, December). During autumn, however, the
      sferics activity was correlated with the occurrence of migraine-type headaches
      (r=0.33, P<0.01) recorded by 37 women who had filled out a headache diary over a
      period of 6 months (July-December). While the thunderstorm activity was very
      intense during July and August, no relationship between sferics and migraine was
      found. In summer, tension-type headaches were associated with meteorological
      parameters such as temperature (r=0.42, P<0.01) and vapour pressure (r=0.28,
      P<0.05). Although the sferics activity can explain a small percentage of the
      variation in migraine occurrence, a direct influence was more likely exerted by
      visible or otherwise perceptible weather conditions (thunderstorms, humidity,
      vapour pressure, warm sector, etc.) than by the sferics activity itself.

PMID- 11594632
TI  - Predicting days of high allergenic risk during Betula pollination using weather
      types.
AB  - The aim of this study was to build up a picture of the influence of
      meteorological conditions on pollen and pollinosis, taking account of weather
      types, pollen concentrations in the air and pollinosis symptoms, with the aim of
      preventing allergic responses. The study took place in Burgundy from 1996 to
      1998, during the pollination of the birch (Betula), which is the most important
      arborean allergen in this region. We used daily pollen data from four Hirst
      volumetric traps, identified weather types by Benichou's classification, and
      obtained data on the occurrence of rhinitis, conjunctivitis, asthma and coughing
      from a sample of 100 patients. These data were analysed by multiple-component
      analysis. The results show that pollen dispersal is favoured by windy conditions,
      low relative humidity, precipitation below 2 mm and temperatures above 6 degrees
      C. Such weather also favours pollinosis, but other particular meteorological
      situations, even if they do not assist pollen dispersal, can act directly on the
      development of symptoms: a decrease of temperature (3 degrees C) led to the
      development of rhinitis and conjunctivitis, while strong winds were associated
      with many cases of conjunctivitis and asthma, owing to the irritant effect of
      cold or wind; asthma was favoured by temperature inversions with fog, probably
      because such weather corresponds to high levels of pollution, which act on
      bronchial hyperreactivity. Because the weather types favouring pollination and
      pollinosis are predicted by the meteorological office, this can constitute a tool
      for reducing the effect of high-risk allergenic days.

PMID- 11594633
TI  - The meteorological sensitivity of ischaemic heart disease mortality events in
      Birmingham, UK.
AB  - Winter ischaemic heart disease (IHD) mortality events (ME) were identified in
      order to establish their degree of meteorological sensitivity. Sensitivity was
      evaluated using regression of surface meteorological and large-scale atmospheric
      circulation variables on daily mortality for each mortality event. Critical
      meteorological variables affecting IHD mortality appear to be local surface dry
      bulb and dew-point temperature and large-scale southerly and westerly wind
      components, atmospheric pressure and vorticity. The rate of change and departure
      from normal conditions of these variables appear to be especially important for
      engendering IHD mortality events. Associated with IHD mortality are two broad
      types of weather conditions: (1) blustery westerly flows and rapidly changing
      weather from the west and (2) climatologically strong northeasterly to
      southeasterly flows of cold air, which bring rapidly changing and anomalous
      thermal conditions to the study area. The general atmospheric circulation
      patterns that produce these conditions are identified and the implications of
      results for weather and health studies are discussed.

PMID- 11594634
TI  - Computer prediction of human thermoregulatory and temperature responses to a wide
      range of environmental conditions.
AB  - A mathematical model for predicting human thermal and regulatory responses in
      cold, cool, neutral, warm, and hot environments has been developed and validated.
      The multi-segmental passive system, which models the dynamic heat transport
      within the body and the heat exchange between body parts and the environment, is
      discussed elsewhere. This paper is concerned with the development of the active
      system, which simulates the regulatory responses of shivering, sweating, and
      peripheral vasomotion of unacclimatised subjects. Following a comprehensive
      literature review, 26 independent experiments were selected that were designed to
      provoke each of these responses in different circumstances. Regression analysis
      revealed that skin and head core temperature affect regulatory responses in a
      nonlinear fashion. A further signal, i.e. the rate of change of the mean skin
      temperature weighted by the skin temperature error signal, was identified as
      governing the dynamics of thermoregulatory processes in the cold. Verification
      and validation work was carried out using experimental data obtained from 90
      exposures covering a range of steady and transient ambient temperatures between 5
      degrees C and 50 degrees C and exercise intensities between 46 W/m2 and 600 W/m2.
      Good general agreement with measured data was obtained for regulatory responses,
      internal temperatures, and the mean and local skin temperatures of unacclimatised
      humans for the whole spectrum of climatic conditions and for different activity
      levels.

PMID- 11594635
TI  - Social context as a focus for rehabilitation.
AB  - In some illnesses activity limitation is determined as much (or even more) by
      cultural factors as it is by the specific disease pathology or impairments
      experienced. There is now some evidence that cultural attitudes and expectations
      can be changed to reduce the burden of disability. This empirical evidence
      supports the WHO ICIDH-2 model of illness and the importance of contexts as
      intervening variables in the development and maintenance of disability.

PMID- 11594636
TI  - Effects of balance training in elderly people with nonperipheral vertigo and
      unsteadiness.
AB  - OBJECTIVE: To evaluate the effect of balance training in group in elderly people
      with nonperipheral vertigo and unsteadiness. DESIGN: Randomized controlled study.
      SETTING: Ear-, nose- and throat department, University Hospital, Sweden.
      SUBJECTS: Twenty-three elderly subjects with nonperipheral vertigo and/or
      unsteadiness randomized into training group and control group. INTERVENTION: The
      training group attended balance training in group twice a week for eight weeks.
      MAIN OUTCOME MEASURES: Timed static balance tests, walking tests and six sensory
      organization tests on EquiTest dynamic posturography were performed before and
      after the training period. Besides, the patients estimated their vertigo and
      unsteadiness on a visual analogue scale (VAS) before and after the training
      period. RESULTS: The training group improved significantly in standing on one leg
      with eyes open, walking forward on a line, walking speed, in three out of six
      tests on dynamic posturography and estimated less vertigo and unsteadiness
      measured with VAS. No changes were seen in the control group. CONCLUSION: Balance
      training in elderly people with nonperipheral vertigo and unsteadiness seems to
      improve both objective and perceived balance.

PMID- 11594637
TI  - Reality orientation therapy to delay outcomes of progression in patients with
      dementia. A retrospective study.
AB  - OBJECTIVE: To evaluate the impact of continued Reality Orientation Therapy (ROT)
      in delaying the outcomes of dementia progression. DESIGN: Retrospective study.
      Data collection was based on review of clinical charts and on telephone
      interviews performed with patients or primary caregivers. SETTING: Day hospital
      of the Alzheimer's Disease Unit, Brescia (Italy). SUBJECTS: Seventy-four patients
      enrolled in at least one cycle of ROT from 1994 to 1998 were studied.
      INTERVENTIONS: Rehabilitative intervention based on formal ROT. MAIN OUTCOME
      MEASURES: This study analysed the time to the occurrence of any of the following:
      cognitive decline on Mini-Mental State Examination scores, urinary incontinence
      as an index of functional decline, institutionalization, and death. RESULTS: Data
      on a 30-month period after the first ROT session were analysed. We compared 46
      patients (treatment group) who completed from 2 to 10 ROT cycles (corresponding
      to 8-40 weeks of training; mean = 15.48) with 28 patients (control group) who
      completed only one ROT cycle (4 weeks). Treatment group showed higher estimated
      survival rates than control group on cognitive decline (p = 0.022) and
      institutionalization (p = 0.002). The relative risks for cognitive decline and
      institutionalization in the control group compared with treatment group were 0.60
      (p = 0.014), and 0.42 (p = 0.021), respectively. CONCLUSIONS: Continued ROT
      classes during the early to middle stages of dementia may delay nursing home
      placement and slow down the progression of cognitive decline.

PMID- 11594638
TI  - Differences in treatment outcome between subgroups of patients with chronic low
      back pain using lumbar dynamometry and psychological aspects.
AB  - OBJECTIVE: To investigate whether subgroups of patients with chronic low back
      pain show differences in treatment outcome, measured with the Roland Disability
      Questionnaire. (RDQ). SETTING: The study was carried out in a rehabilitation
      centre. SUBJECTS: Eighty-four patients with chronic low back pain participated in
      this study. INTERVENTION: Patients followed a multidisciplinary treatment
      programme that primarily targets physical aspects. DESIGN AND MAIN OUTCOME
      MEASURE: Based on pretreatment lumbar dynamometry results and Symptom Checklist
      (SCL-90) scores, patients were divided into subgroups. The dynamometry subgroups
      were: performances lower than healthy subjects (expected performance),
      performances comparable with those of healthy subjects (normal performance) and
      inconsistent performances (submaximal performance). The SCL-90 subgroups were: a
      total score of 'average' or lower compared with a population of chronic pain
      patients (low psychological score) and a total score of 'above average' or higher
      compared with this population (high psychological score). Patients answered the
      RDQ in the week before (RDQ1; n = 84) and after treatment (RDQ2; n = 78) to
      investigate whether the subgroups show differences in outcome expressed as the
      percentage change between RDQ2 and RDQ1, (%RDQ2-1). A %RDQ2-1 > or = 20% was
      classified as an improvement. RESULTS: Improvement on disability level > or = 20%
      is shown in 64% and 55% of the patients with 'normal' and 'expected' lumbar
      dynamometry performances and low psychological scores compared with only 33% and
      25% of those with high psychological scores. Patients with submaximal
      performances show hardly any changes in disability level and there are no
      differences betweenthose with low psychological scores (14%) and those reporting
      high scores (0%). CONCLUSION: The fact that patient subgroups with differences in
      treatment outcome can be defined using lumbar dynamometry and psychological
      questionnaires suggests that these instruments might facilitate treatment
      indication in clinical practice.

PMID- 11594639
TI  - Psychometric properties of the Minnesota Living with Heart Failure Questionnaire
      (MLHF-Q).
AB  - OBJECTIVE: To evaluate the psychometric properties of the Minnesota Living with
      Heart Failure Questionnaire (MLHF-Q) in patients with atrial fibrillation.
      DESIGN: A prospective study of the patients who underwent DC electrical
      cardioversion. SETTING: Clinics of cardiology and thoracic surgery of the
      University Hospital in Groningen, the Netherlands. MAIN OUTCOME MEASURES: The
      disease-specific MLHF-Q and generic measures of quality of life were
      administered. The sensitivity to change over time was tested with effect sizes
      (ES). Internal consistency of MLHF-Q scales was estimated with Cronbach's alpha.
      To evaluate the construct validity multitrait-multimethod analysis was applied.
      The 'known group validity' was evaluated by the comparison of mean scores and
      effect sizes between two groups of the New York Heart Association (NYHA)
      classification (NYHA I versus II-III). Stability of MLHF-Q scales was estimated
      in a subgroup of patients who remained stable. Perfect congruence analysis and
      factor analysis were applied to confirm the a priori determined structure.
      RESULTS: Cronbach's alpha was > or = 0.80 of the MLHF-Q scales. Perfect
      congruence analysis (PCA) showed that the results resemble quite well the a
      priori assumed factor structure. Multitrait-multimethod analysis showed
      convergent validity coefficients ranging from 0.59 to 0.73 (physical impairment
      dimension) and 0.39 to 0.69 (emotional dimension). The magnitude of change can be
      interpreted as medium (ES = 0.50). The results of a 'test-retest' analysis in a
      stable group can be valued as satisfactory for the MLHF-Q scales (Pearson's r >
      0.60). The physical dimension and the overall score of the MLHF-Q discriminated
      significantly between the NYHA I and II-III groups (p < 0.001) with large effect
      sizes (ES > 1.0).

PMID- 11594640
TI  - The effects of increased rehabilitation therapy after brain injury: results of a
      prospective controlled trial.
AB  - OBJECTIVE: The objective was to investigate the effect of increased intensity of
      rehabilitation therapy provided to brain-injured subjects on the rate at which
      independence was regained and the duration of hospital admission. DESIGN: A two
      centre, prospective, controlled study with random allocation to groups. SETTING:
      Two district general hospitals on the south coast of England. SUBJECTS: Fifty-six
      people with moderate and severe head injury consecutively admitted to Southampton
      and Poole hospitals between June 1995 and September 1997. INTERVENTIONS:
      Increased intensity of rehabilitation therapy input without change in content.
      RESULTS: Subjects receiving more intensive therapy made more rapid progress and
      were discharged home sooner. The different intensities of therapy employed in
      this study showed no evidence of a 'ceiling' effect and the 'intervention group'
      made significantly more rapid progress on tests of dependency during the period
      of admission. A clear response to increased therapy input was seen in one of the
      centres with more rapid functional improvement and a shorter length of hospital
      stay. This centre already had more therapy and better community facilities. No
      such benefits were seen at the other centre where the intervention group had a
      longer hospital stay than the routine group. CONCLUSION: Increasing the hours per
      week of therapy given to adults recovering from brain injury in hospital can
      accelerate the rate of recovery of personal independence and result in their
      being discharged from hospital sooner. Increased rehabilitation therapy after
      brain injury is associated with enhanced functional recovery and shorter hospital
      stay if provided in the context of an integrated service that can provide ongoing
      community support. There is no evidence of any ceiling effect of therapeutic
      intensity beyond which no further response is observed.

PMID- 11594642
TI  - Disability test 10 days after acute stroke to predict early discharge home in
      patients 65 years and older.
AB  - OBJECTIVE: To identify prognostic instruments for the planning of care after
      acute stroke. DESIGN: Prospective study. SETTING: Stroke unit and geriatric
      rehabilitation unit. SUBJECTS: One hundred and fifteen consecutive acute stroke
      patients > or = 65 years old. MAIN OUTCOME MEASURES: Univariate and multivariate
      survival analyses. Length of hospital stay and residential form up to three
      months after onset. RESULTS: The average length of stay was significantly shorter
      if age <80 years, male, living with another person, normal sensory ability,
      Barthel Index (BI) score > or = 35 and Rivermead Mobility Index (RMI) score > or
      = 4, assessed 10 days after onset. Multivariate analysis, also including BI
      subtests, showed that RMI score > or = 4, which corresponds to the ability to
      rise from a chair in less than 15 seconds and remain erect for 15 seconds with or
      without aid, 10 days after onset, had the greatest impact on early discharge home
      after acute stroke, together with normal bladder function (BI subtest six),
      normal sensory ability and living with another person. CONCLUSION: The best
      predictor of early discharge home, 10 days after stroke onset, was the ability to
      rise from a chair with or without aid. This simple and quickly conducted test
      requires no special equipment and in the present study had a very high predictive
      value.

PMID- 11594641
TI  - Walking training of patients with hemiparesis at an early stage after stroke: a
      comparison of walking training on a treadmill with body weight support and
      walking training on the ground.
AB  - OBJECTIVE: To compare the effect of walking training on a treadmill with body
      weight support (BWS) and walking training on the ground at an early stage of
      rehabilitation in patients with hemiparesis after stroke. DESIGN: Randomized
      controlled experimental study. SETTING: Multicentre design; three departments of
      rehabilitation medicine. SUBJECTS: Seventy-three consecutive first stroke
      patients admitted to a rehabilitation clinic were randomized into a treatment
      group and a control group. INTERVENTIONS: The treatment group received walking
      training on a treadmill with BWS for 30 minutes, 5 days a week. The control group
      received walking training according to the Motor Relearning Programme (MRP) on
      the ground for 30 minutes 5 days a week, not including treadmill training. During
      the time in the rehabilitation department (about two months), all patients in the
      study also received professional stroke rehabilitation besides the walking
      training in the two groups. MAIN OUTCOME MEASURES: Functional Independence
      Measure (FIM), walking velocity for 10 m, Functional Ambulation Classification
      (FAC), Fugl-Meyer Stroke Assessment and Berg's Balance Scale. The assessments
      were performed at admission, at discharge and at 10-month follow-up. RESULTS:
      There were no statistically significant differences between the groups at
      discharge or at the 10-month follow-up with regard to FIM, walking velocity, FAC,
      Fugl-Meyer Stroke Assessment, and Berg's Balance Scale. Patients in both groups
      improved in these variables from admission to the 10-month follow-up.
      CONCLUSIONS: Treadmill training with BWS at an early stage of rehabilitation
      after stroke is a comparable choice to walking training on the ground.

PMID- 11594643
TI  - Can brain-injured patients participate in an aerobic exercise programme during
      early inpatient rehabilitation?
AB  - OBJECTIVE: We investigated the capacity of brain-injured patients to participate
      in an aerobic exercise programme early after injury. DESIGN: Retrospective
      analysis of exercise achievements in patients participating in a randomized
      controlled trial. SETTING AND SUBJECTS: Ninety patients participated in an
      exercise training programme on a cycle ergometer at four inpatient neurological
      rehabilitation units for younger patients. At intake, impairments and function
      were rated on: Motricity Index, Ashworth Scale, Berg Balance Scale, Barthel Index
      and Functional Independence Measure. INTERVENTIONS: Patients cycled for up to 30
      minutes three times weekly for 24-36 sessions over 12 weeks. MAIN OUTCOME
      MEASURES: Exercise performance was measured by: (a) number of sessions to achieve
      a cycling time of 30 minutes, (b) overall mean cycling time per session over 24
      sessions and (c) mean time per session cycling at >60% of age predicted maximum
      heart rate (HR max) over 24 sessions. RESULTS: Fifty-five patients completed 24
      sessions. Thirty-five withdrew, largely for logistic reasons, before completing
      training; they were significantly less disabled than the 55 who remained. Forty
      four of the 55 patients trained for an average of at least 20 minutes per
      session, 18 training at >60% HR max for this time. There were no differences in
      performance on the three exercise parameters between two groups of patients with
      baseline Barthel scores of < or = 12 and > or = 13. CONCLUSIONS: Brain-injured
      patients with a range of disabilities have the capacity to participate in an
      exercise programme during early inpatient rehabilitation, though some may take
      longer to achieve adequate intensity of aerobic exercise.

PMID- 11594644
TI  - Can the site of brain lesion predict improved motor function after low-TENS
      treatment on the post-stroke paretic arm?
AB  - OBJECTIVES: Previous reports suggest that afferent stimulation improves arm motor
      function in patients suffering from stroke. The aim of this pilot study was to
      test the hypothesis that the brain lesion location determines the response to low
      frequency (1.7 Hz) transcutaneous electric nerve stimulation (Low-TENS) therapy.
      DESIGN: Magnetic resonance imaging (MRI) was performed on 14 patients who had
      previously received Low-TENS on the paretic arm after stroke. METHODS: MR images
      were classified with two different methods. First, lesions in the cortical and
      the subcortical areas were registered. Secondly, any change in a described
      periventricular white matter (PVWM) area was recorded. Interactions between the
      lesion site, as detected by MRI, and response to Low-TENS treatment were
      analysed. RESULTS: Arm motor function after Low-TENS treatment in relation to
      lesion in different brain areas showed that absence of lesions in the PVWM area
      increased the possibility for improved motor capacity after afferent stimulation.
      CONCLUSIONS: The site of lesion may play a role in prognosis/outcome after Low
      TENS treatment but this hypothesis should be further tested in a larger
      prospective study.

PMID- 11594645
TI  - Factors determining participation in young adults with a physical disability: a
      pilot study.
AB  - OBJECTIVES: To evaluate in a pilot study the usefulness of measures of health and
      psychosocial status for use with young people with physical and complex
      disability. Also to test empirically a conceptual model of the factors
      determining key outcomes in young disabled adults, in particular, participation
      (handicap). DESIGN: A cross-sectional study involving face-to-face interviews
      with young adults aged 16-28 years (n = 45) with physical and complex
      disabilities. A group of nondisabled college students completed the same set of
      questions to provide normative scores for some psychosocial measures. SETTING:
      Young people with physical disabilities were recruited from the area of North and
      North East Lincolnshire, and nondisabled young people from the Leeds area.
      METHODS: Standardized measures of impairment, disability and handicap, together
      with various psychosocial scales were incorporated into a structured face-to-face
      interview. Standardized measures included the Nottingham Health Profile (NHP),
      the Barthel Index, the London Handicap Scale, Rosenberg's Self-esteem Scale and
      the Proactive Scale. RESULTS: Regression analysis showed the most important
      predictors of participation were energy and pain (NHP), disability (Barthel) and
      self-efficacy. Most of the health status measures were able to discriminate
      between disabled and nondisabled young people, but some measures lacked face
      validity for the 'nonwalking' disabled group. CONCLUSIONS: Both health status and
      psychosocial factors were found to impact on the participation of young people.
      Impairment and disability however, did not impact adversely on self-ratings of
      health or quality of life and it is clear from these results that having a
      disability may limit participation, but is not necessarily synonymous with a
      poorer quality of life.

PMID- 11594646
TI  - Regional variations in stroke care in England, Wales and Northern Ireland:
      results from the National Sentinel Audit of Stroke. Royal College of Physicians
      Intercollegiate Stroke Working Party.
AB  - STUDY OBJECTIVE: To identify the variations between regions in England, Wales and
      Northern Ireland in the case-mix, organization and process of care for stroke.
      DESIGN: Retrospective audit of case notes and service organization. SETTING: Two
      hundred and ten Trust sites from 197 Trusts in 10 Health Regions in England,
      Wales and Northern Ireland. PATIENTS: The 6894 consecutive stroke patients
      admitted between 1 January and 31 March 1998 (up to 40 per Trust). Audit tool:
      The Intercollegiate Stroke Audit. RESULTS: There are significant differences in
      stroke care between regions that cannot be explained by known case-mix or
      clinical variables. The proportion of patients spending more than half their
      hospital stay in stroke unit care varied between regions from 10% to 27%. Thirty
      day mortality in different regions ranged between 21% and 33%.
      Institutionalization rates for those admitted from home varied between 6% and
      19%. Similar variations existed in discharge disability and length of stay.
      CONCLUSIONS: There were widespread variations in specialist service provision for
      stroke in different regions. Regional variation in 30-day mortality and in
      institutionalization after stroke is not explained by clinical factors and
      therefore may represent different local health care policies and expectations.

PMID- 11594647
TI  - Research into rehabilitation: the priorities?

PMID- 11594648
TI  - Invited editorial: on estimates of population radiation exposure.

PMID- 11594649
TI  - Exposure of red bone marrow to ionising radiation from natural and medical
      sources in France.
AB  - This paper presents a review of available data on the average level of equivalent
      dose to the red bone marrow in France, due to natural and some medical exposures.
      The sources of exposure to ionising radiation which were studied are medical
      examinations involving x-rays (diagnostic radiology), inhalation of radon and
      thoron, cosmic irradiation, terrestrial irradiation and intakes of natural
      radionuclides. This review is based, where possible, on specific data for France.
      The influence of age on exposure levels is studied when data are available. The
      total equivalent dose to the red bone marrow is estimated at 2.4 mSv year(-1),
      2.7 mSv year(-1) and 5.4 mSv year(-1) respectively for adults (> or =18 years
      old), children (3-17 years old) and infants (0-1 year old). The high level of
      exposure for infants is explained by the important contribution of 210Po. The
      average equivalent dose to the red bone marrow for adults is also compared with
      the average committed effective dose due to the same exposure sources. The
      importance of medical exposure and natural exposure due to intake of natural
      radionuclides emphasises the importance of obtaining more information about these
      sources of exposure.

PMID- 11594650
TI  - The mortality and cancer morbidity experience of employees at the Chapelcross
      plant of British Nuclear Fuels plc, 1955-95.
AB  - The results presented here are from the follow-up of the cohort of workers ever
      employed at the Chapelcross site of British Nuclear Fuels plc (BNFL) between 1955
      and 1995. The study cohort consists of 2628 workers, 2249 of whom were male, who
      were first employed at the plant before 1 January 1996, and who have 63967 person
      years of follow-up. The mean follow-up period is 24.3 years. The 2209 members of
      the cohort (84%) classified as radiation workers accumulated 185.1 person
      sieverts of external radiation; their median cumulative dose was 39.1 mSv, and
      95% of their cumulative doses were less than 339.3 mSv. The Chapelcross workers
      show the usual 'healthy worker' effect. To the end of 1995, there were 528 deaths
      among the total cohort (20%), including 449 (20%) amongst the radiation workers.
      When the dose was unlagged, a statistically significant association was noted
      between cancer registrations of the buccal cavity and pharynx and dose, based on
      five cases. When the dose was lagged by 10 years, a statistically significant
      excess relative risk was noted between all cancer morbidity and dose, 1.80 Sv(-1)
      (0.03 to 4.45), based on 162 cases. This result is driven by the non-significant,
      but high excess relative risk estimates from the 12 prostatic cancer
      registrations. A statistically significant association is noted between the eight
      deaths amongst radiation workers who had prostatic cancer as the underlying cause
      of mortality and cumulative external radiation dose when the dose was lagged by
      0, 2 and 10 years. The association is unlikely to be causal. The finding has
      little biological plausibility as the strength of the association weakened as the
      dose lagging increased; it was strongest when the dose was unlagged and
      disappeared when the dose was lagged by 20 years. None of the workers who was
      registered for or died from prostatic cancer had ever been monitored for exposure
      to tritium or to 51Cr, 59Fe, 60Co or 65Zn. There is no evidence to date amongst
      the Chapelcross cohort of increased risk for cancers considered to be radiogenic
      based on studies of populations exposed to high levels of radiation.

PMID- 11594651
TI  - Electromagnetic radiation from microwave ovens.
AB  - Electromagnetic radiation from microwave ovens in Saudi Arabia was investigated
      by means of a field measurement survey. The survey was carried out for 106 ovens
      used in households and restaurants in Riyadh city. Ovens were between 1 month and
      14 years old with operating power ranging from 0.5 to 4.4 kW. One oven was found
      to leak more than the 5 mW cm(-2) limit specified in the standard. Fifteen other
      ovens were found to leak 1 mW cm(-2) or more, with the remaining ovens leaking
      less than that. Based on the survey result, previous studies and the fast decay
      of radiated power density with distance from the oven, the conclusion was that
      user exposure to RF radiation from microwave ovens is much less than the general
      public exposure limit set by most international standards at 2450 MHz, i.e. 1 mW
      cm(-2), and that a detrimental effect on health is an unlikely result of exposure
      to radiation from microwave ovens.

PMID- 11594652
TI  - Airborne radon and its progeny levels in the coal mines of Godavarikhani, Andhra
      Pradesh, India.
AB  - In India, out of about 0.7 million miners, nearly 0.5 million persons are
      directly engaged in coal operations. Radon and its progeny levels have been
      quantified in the coal-mining environment of Godavarikhani, Andhra Pradesh, India
      using solid-state nuclear track detectors. Seasonal and mine depth variations in
      radon levels have been recorded resulting in the identification of locations with
      a high radon level as areas with no mining activity, active mining operational
      zones and return air ventilation paths. All these radon levels were below the
      permissible levels. The average concentrations of radon and its progeny levels
      were found to be 144 +/- 61 Bq m(-3) and 20 +/- 11 mWL (working level)
      respectively in the two-incline mine, and these values for the five-incline mine
      are recorded as 315 +/- 71 Bq m(-3) and 30 +/- 9 mWL respectively.

PMID- 11594653
TI  - Effect of a vitamin D3-based nutritional supplement ('Videchol') on carbohydrate
      metabolism of rats following chronic low dose-rate irradiation.
AB  - In this study we evaluated the effects of the administration of a vitamin D3
      preparation 'Videchol' to chronically irradiated rats (1 cGy day(-1)) by the
      assessment of the activities of several glycolytic enzymes: lactic dehydrogenase
      (LDH) (EC 1.1.1.28), pyruvate kinase (PK) (EC 2.7.1.40) and hexokinase (HK) (EC
      2.7.1.1), in populations of erythroid and myeloid bone marrow cells. Videchol
      treatment of irradiated rats led to the normalisation of HK and LDH activity at
      cumulative doses of around 30 cGy in granulocyte-monocyte cells and to
      normalisation of LDH and PK activities in erythroid cells starting at 20 cGy in
      comparison with irradiated rats who did not receive Videchol. The reaction
      kinetic parameters of LDH in erythrocytes changed according to the redistribution
      pattern of the isozymes throughout the different stages of the experiment. The
      administration of Videchol to irradiated rats led to a rearrangement of the LDH
      isozymes ratio characterised by kinetic properties more comparable to those of
      the controls. Thus, vitamin D3 appears to induce a normalisation of carbohydrate
      metabolism in rats chronically irradiated with low dose-rate ionising radiation.

PMID- 11594654
TI  - Contribution of the French Society for Radiation Protection to the current
      reflections on the possible improvements to the radiological risk management
      system.
AB  - Following the invitation from IRPA to comment on the article written by Professor
      Roger Clarke entitled 'Control of low-level radiation exposure: time for a
      change?', the Board of the French Society for Radiation Protection (SFRP) decided
      to set up a working group on 'controllable dose'. The latter, which worked from
      April 1999 to July 2000, consisted of some 20 members representing the
      stakeholders involved in radiological protection in France: authorities, experts
      and professionals from nuclear, medical and research fields as well as associated
      bodies. The working group first examined the current hypotheses on radiological
      risk and noted their relevance to the practical management of such a risk. Then a
      list of the different exposure situations and their associated characteristics
      was elaborated in tabular form, followed by a discussion on the situations when
      the system of radiological protection works well, less well or badly,
      particularly through the implementation of the general principles of radiological
      protection. The working group finally made proposals to ICRP for the evolution of
      the system in a more workable direction.

PMID- 11594655
TI  - Towards the ICRP's new recommendations--problems in dosimetry.

PMID- 11594656
TI  - ICRP's new recommendations.

PMID- 11594657
TI  - The future of the ICRP recommendations.

PMID- 11594658
TI  - Is the endeavour justified?

PMID- 11594659
TI  - Healthy worker effect.

PMID- 11594660
TI  - IARC classification of static and extremely low frequency electric and magnetic
      fields (volume 80 of the IARC monographs series).

PMID- 11594661
TI  - New review of radiation risk models.

PMID- 11594662
TI  - Manchester company fined 35,000 pounds sterling after radioactive source goes
      missing.

PMID- 11594663
TI  - SRP annual general meeting: health physics instrumentation and analytical
      techniques. Edinburgh, 24-26 April 2001.

PMID- 11594664
TI  - VALDOR symposium addressing transparency in risk assessment and decision making.
      Stockholm, 10-14 June 2001.

PMID- 11594665
TI  - Sealed sources-producer responsibilities meeting. Bristol, 14 May 2001.

PMID- 11594666
TI  - The health hazards of depleted uranium. London, 13 June 2001.

PMID- 11594667
TI  - Acne. Introduction.

PMID- 11594668
TI  - The evolving role of Propionibacterium acnes in acne.
AB  - Propionibacterium acnes is a member of the resident cutaneous flora. Sebaceous
      follicles involved in acne are characterized by the accumulation of abnormally
      desquamated corneocytes and excess sebum-the microcomedo. This environment
      provides ideal growth conditions for P acnes. Several orders of magnitude level
      of P acnes are found in microcomedos. P acnes produces a variety of chemotactic
      factors and proinflammatory molecules that are responsible for the inflammatory
      phase of acne. Antibiotic therapy works by reducing the viable number of P acnes
      as well as by reducing the production of inflammatory stimuli. Antibiotic therapy
      has been a mainstay of treatment for more than 30 years. In the last decade,
      decreased sensitivity to antibiotics has developed and clinical resistance has
      been described. This development threatens the usefulness of antibiotic therapy
      in the future.

PMID- 11594669
TI  - Hormones and acne: pathophysiology, clinical evaluation, and therapies.
AB  - Hormonal aspects of acne are of particular interest in treating adult women. A
      review of the role of hormones in the pathogenesis of acne, guidelines for the
      workup of a suspected endocrine disorder, and an overview of the use of hormonal
      therapy in women with endocrine problems and in normal women is presented.

PMID- 11594670
TI  - Developments in topical retinoid therapy for acne.
AB  - Topical retinoic acid was introduced for acne treatment three decades ago. Since
      that time, researchers have discovered thousands of retinoids, originally defined
      as chemical analogs of vitamin A. After the identification of nuclear retinoid
      receptors in 1987, the definition of this class expanded to include molecules
      that bind to and activate such receptors. The receptor-selective retinoid agents,
      adapalene and tazarotene, were developed in the 1990s. Other innovations of the
      past decade include retinoid formulations and methods aimed at limiting retinoid
      absorption. Cutaneous irritation may be reduced without losing retinoid efficacy
      by inhibiting retinoid penetration into the deep epidermis and dermis. Examples
      include tretinoin in slow-release vehicles and the short-contact method of
      tazarotene gel therapy. Only trace amounts of adapalene are absorbed after
      topical application, perhaps explaining its relatively low irritancy. New
      formulations of existing agents, such as additional concentrations of tretinoin
      in microsphere gel and cream formulations of tazarotene, are now under
      investigation for acne. Current research focused on receptor selectivity holds
      the promise of yielding new retinoid molecules with improved benefits and safety.

PMID- 11594671
TI  - Isotretinoin dosing: past, present, and future trends.
AB  - Isotretinoin is the treatment of choice for severe nodulocystic acne. It
      represents the sole agent that effectively addresses all of the
      pathophysiological factors in the production of acne. Dosing recommendations are
      based on European trials that included patients with nonacne skin disease, which
      requires higher doses of isotretinoin for clearance. In this article, the authors
      relate their extensive experience with dosing regimens for acne as well as
      discuss recommendations for length of therapy.

PMID- 11594672
TI  - Safety issues in isotretinoin therapy.
AB  - Isotretinoin (Accutane, Roche Laboratories Inc, Nutley, NJ) is an important drug,
      not only for the treatment of severe acne, but also for other diagnoses and in
      chemoprevention settings. Because the use of isotretinoin is increasing, it is
      important for physicians to be aware of the adverse events, toxicities, and
      management issues related to its use. The most important issue is that of
      congenital defects, which has resulted in new pregnancy prevention policies and
      programs implemented by the manufacturer. A relatively new concern is that of
      depression associated with isotretinoin use, also resulting in new policies
      placed by the manufacturer and the FDA. The most common adverse effects observed
      during treatment are mucocutaneous and ocular in nature, but laboratory
      abnormalities and effects in the nervous, musculoskeletal, gastrointestinal,
      pulmonary, hematologic, and other systems are also described. Additionally,
      potential drug interactions, follow-up, and toxicity prevention measures are
      discussed.

PMID- 11594673
TI  - Acne therapy: clinical pearls.
AB  - Several classes of medications successfully treat acne. Systemic and topical
      retinoids, systemic and topical antimicrobials, and systemic hormonal therapy are
      the major categories. Failure of therapy may result from drug interactions,
      antibiotic resistance, or coexisting conditions; therefore, a detailed history
      including these points should be used to decide which therapy is appropriate for
      each patient. Furthermore, one must consider the potential side effects of each
      treatment and make sure that (1) the benefits outweigh the risks of the
      treatment, (2) the side effects can be avoided by adding another agent, or (3)
      the side effects can be safely treated.

PMID- 11594674
TI  - Treatment of acne scarring.
AB  - One of the most distressing side effects of acne vulgaris is the development of
      acne scars. In this article, the authors discuss the history of and current
      modalities in use for the treatment of acne scars. The discussion includes
      resurfacing, dermabrasion, laser surgery, peels, punch excisions, and the use of
      fillers.

PMID- 11594675
TI  - Rosacea: current thoughts on origin.
AB  - Rosacea is a clinical pattern beginning and evolving in the genetically
      susceptible individual in response to a host of exposures. It produces a variety
      of clinical presentations, which vary over time and with age. Recently, many
      specific mediators of rosacea development have been described. A primary genetic
      cause for rosacea is suggested as single genes often control such mediators:
      enzymes, neuroendocrine transmitters, and cytokines are found in pathways to
      rosacea signs and symptoms. Currently, neither a specific cause nor a laboratory
      indicator of rosacea has been suggested. However, broadening interest in rosacea
      portends future increase in knowledge.

PMID- 11594676
TI  - Treatment of rosacea.
AB  - Rosacea is an inflammatory disease of the face and eyes. Treatment is adjusted to
      the site of the disease and its severity.

PMID- 11594677
TI  - Cosmetics in acne and rosacea.
AB  - Cosmetics that are appropriate for use in patients with rosacea and acne must be
      noncomedogenic, nonacnegenic, nonirritating, and hypoallergenic. This requires a
      basic understanding of cosmetic fromulation and the selection of products that
      meet guidelines for sensitive skin.

PMID- 11594678
TI  - Antiviral beta-L-nucleosides specific for hepatitis B virus infection.
AB  - Three simple, related nucleosides, beta-L-2'-deoxycytidine (LdC), beta-Lthymidine
      (LdT), and beta-L-2'-deoxyadenosine (LdA), have been discovered to be potent,
      specific and selective inhibitors of the replication hepatitis B virus (HBV), as
      well as the closely related duck and woodchuck hepatitis viruses (WHV). Structure
      activity relationship analysis indicates that the 3'-OH group of the beta-L-2'
      deoxyribose of the beta-L-2'-deoxynucleoside confers specific anti-hepadnavirus
      activity. The simple nucleosides had no effect on the replication of 15 other RNA
      and DNA viruses, and did not inhibit human DNA polymerases (alpha, beta and
      gamma) or compromise mitochondrial function. The nucleosides are efficiently
      converted intracellularly into active triphosphate metabolites that have a long
      half-life. Once-daily oral administration of these compounds in the woodchuck
      efficacy model of chronic HBV infection reduced viral load by as much as 10(8)
      genome equivalents/ml serum and there was no drug-related toxicity. In addition,
      a decline in WHV surface antigen (WHsAg) paralleled the decrease in viral load.
      This class of nucleosides displays an excellent overall safety profile. The first
      compound, LdT, has already entered clinical trials and LdC, currently being
      developed as a prodrug, is expected to enter the clinic in the near future. These
      compounds have the potential for use in combination therapy with the goal of
      achieving superior viral suppression and diminishing the onset of resistance.

PMID- 11594679
TI  - The molecular basis of inhibition and toxicity of modified cytosine analogues
      targetting HIV-1 reverse transcriptase.
AB  - Among the AIDS drugs approved by the US Food and Drug Administration (FDA) for
      clinical use, two are modified cytosine analogues, zalcitabine (ddC) and
      lamivudine [(-)3TC]. (-)3TC is the only analogue containing an unnatural L(
      )nucleoside configuration. Similar to other dideoxynucleosides, these analogues
      are metabolically activated to the triphosphate that is incorporated into DNA by
      HIV-1 reverse transcriptase (RT), resulting in DNA chain termination and
      ultimately cessation of viral replication. The natural d(+)3TC isomer also acts
      in a similar manner to inhibit HIV-1 RT. In cell culture (-)3TC is less toxic
      than its d(+)isomer (+)3TC, containing the natural nucleoside configuration, and
      both are considerably less toxic than ddC. The mechanistic basis for the
      stereochemical selectivity and differential toxicity of the isomeric 3TC and ddC
      compounds is not completely understood, although a number of factors may clearly
      come into play. We have previously investigated the mechanistic basis for the
      differential stereoselective inhibition and toxicity of these three cytosine
      analogues by comparing the effects of ddCTP (+)3TC-TP and (-)3TC-TP on the HIV-1
      RT, as well as a recombinant form of the human mitochondrial DNA polymerase
      (Polgamma), the holoenzyme polymerase responsible for mitochondrial DNA
      replication. In this paper, we discuss the molecular mechanism for the
      stereochemical selectivity and differential toxicity.

PMID- 11594680
TI  - Evaluation of novel strategies to combat hepatitis B virus targetting wild-type
      and drug-resistant mutants in experimental models.
AB  - Recent studies have shown that the kinetics of hepatitis B virus (HBV) clearance
      during antiviral therapy are slow, requiring long-term therapy to control viral
      replication. It has also been shown that emergence of resistant mutants is
      accelerated by high HBV replication and hepatocyte turnover, which are common
      features in patients with chronic HBV infection. It is therefore important to
      continue research on novel antiviral agents to design optimal combination
      strategies. The duck and woodchuck models of hepadnavirus infection are currently
      the best models for the investigation of the inhibitory effect of nucleoside
      analogues on wild-type and lamivudine-resistant mutants. Our studies revealed
      that these mutants have a decreased priming and elongation activity, and remain
      sensitive to novel nucleoside analogues. Tissue culture experiments with
      transient transfection of wild-type and mutant viruses also confirmed these data.
      Infection studies in primary hepatocytes and in animal models gave insight into
      the pathobiology of lamivudine-resistant mutants, as well as into the kinetics of
      wild-type virus clearance during antiviral therapy. Furthermore, it appears that
      novel strategies inducing a specific anti-HBV immune response by a DNA vaccine
      approach may induce viral clearance. Altogether, these results suggest that: (i)
      lamivudine-resistant mutants are likely to be cross-resistant to other L-cytidine
      analogues; (ii) antiviral therapy using a single reverse transcriptase (RT)
      inhibitor is likely to fail to eradicate viral covalently closed circular DNA;
      and (iii) new nucleoside analogues with unique mode of action (inhibition of
      priming or elongation of RT, or DNA polymerase activity) and activity against
      lamivudine-resistant strains are emerging. Combination of these new anti-HBV
      agents with DNA based immunization may prove useful to eradicate viral infection.

PMID- 11594681
TI  - RNA polymerase as an antiviral target of hepatitis C virus.
AB  - Hepatitis C virus (HCV) infection is emerging as one of the most prevalent viral
      diseases of medical significance. It afflicts approximately 100 million people
      worldwide. Although HCV infections are mostly clinically inapparent during the
      acute stage, the majority of infected patients develop chronic hepatitis, liver
      cirrhosis and hepatocellular carcinoma. Mainly as a result of ongoing HCV
      epidemics, the incidence of hepatocellular carcinoma and demands for liver
      transplantation have increased at a rapid pace in many countries in the last
      couple of decades. The current therapeutic options for HCV are limited;
      interferon-alpha (IFN-alpha) alone or IFN plus ribavirin are the only available
      treatments. Unfortunately, these treatments are efficacious for only a limited
      number of patients. They are particularly ineffective against genotype 1 HCV,
      which is the most common genotype in developed countries, including most European
      countries, the USA and Japan. Therefore, the development of new therapeutic
      strategies is urgently needed, so that the progression of hepatic diseases in HCV
      infected patients can be halted before serious late-stage illnesses manifest
      themselves. Otherwise, HCV may exact a huge toll on health care budgets and the
      wellbeing of societies in the ensuing decades.

PMID- 11594682
TI  - Predictive efficacy of SCID-hu mouse models for treatment of human
      cytomegalovirus infections.
AB  - There are few animal models to evaluate the in vivo activity of new compounds
      against human cytomegalovirus (HCMV) infections, as virus replication is largely
      limited to human cells. In our studies, we have utilized SCID mice implanted with
      human tissue (SCID-hu) and inoculated with HCMV as models for infections of the
      eye or visceral organs in an immunocompromised host. For the ocular model, fetal
      human retinal tissue was implanted in the anterior chamber of the SCID mouse eye
      and inoculated 6-9 weeks later with 2,000-7,500 plaque-forming units (pfu) of
      HCMV. In the second model, fetal thymus and liver (thy/liv) tissue was implanted
      under the kidney capsule of SCID mice and inoculated 12-14weeks later with 2,200
      9,000 pfu of HCMV. At various times after infection, implant tissues were
      removed, homogenized, and HCMV titres quantified by plaque assay. The replication
      of the Toledo strain of HCMV in both models was similar in that viral titres
      increased through day 21, remained high through day 35, and then gradually
      decreased. To validate the two models, the efficacy of ganciclovir (GCV) and
      cidofovir (CDV) was determined in both ocular and thy/liv model implants. In SCID
      hu retinal tissue, once daily intraperitoneal (i.p.) treatment with 33 mg GCV per
      kg significantly reduced viral titres (2-20-fold) between 14 and 28 days after
      infection. In SCID-hu thy/liv implants, the same treatment regimen reduced viral
      replication either completely or by 3-5 log10. In retinal implant tissue, i.p.
      treatment with 25 mg CDV per kg once daily for 14 days, followed by three times
      weekly for the next 14 days, reduced viral titres by 2-3 log10 between 10 and 42
      days after infection. In comparison, once daily i.p. administration of 30 mg CDV
      per kg completely inhibited HCMV replication in thy/liv implants. These results
      indicate that both the SCID-hu retinal and SCID-hu thy/liv implant models are
      useful for determining in vivo activity against HCMV, and appear to be predictive
      of efficacy for both ocular and systemic infections in humans.

PMID- 11594683
TI  - Cellular proteins (cyclin dependent kinases) as potential targets for antiviral
      drugs.
AB  - Several pharmacological inhibitors that are specific for cellular cyclin
      dependent kinases (cdks) have recently been found to repress viral replication in
      vitro. Thus, replication of human cytomegalovirus, herpes simplex virus, and HIV
      1 is repressed by pharmacological cdk inhibitors (PCIs). Replication of several
      other viruses requires cdks that are sensitive to PCIs. Interestingly, some of
      the PCIs that have antiviral activity in vitro are being tested in animal models
      and in human clinical trials as anti-cancer agents, showing little toxicity in
      vivo. Thus, PCIs have the potential to become antiviral drugs for clinical use.
      As PCIs repress viral replication by targetting cellular proteins, they would
      constitute a novel group of antivirals. They could be active against several
      unrelated viruses, and viral mutants that are resistant to conventional antiviral
      drugs, and could be used in combination with any antiviral drug that targets a
      viral protein. For viral diseases whose pathological mechanism requires cdks,
      such as virus-induced tumours, PCIs would repress both the aetiological agent and
      the pathogenic mechanism. In this review, the biochemical, cellular and antiviral
      activities of PCIs in vitro and their toxicity in vivo are discussed. Other
      cellular proteins that are required for viral replication could also be targets
      for new antiviral drugs.

PMID- 11594684
TI  - Targets of anti-influenza chemotherapy other than neuraminidase and proton pump.
AB  - Antiviral chemotherapy for influenza started with treatment with amantadine and
      then progressed with finding the clinical efficacy of neuraminidase (NA)
      inhibitors. Beside amantadine and NA inhibitors, there are several compounds that
      attack novel targets of influenza virus (FluV) replication. Binding and
      penetration of FluV to cell membrane are important stages in the process of virus
      replication, and several compounds that inhibit these functions have been
      reported, although most of them have yet to be examined for clinical use. A
      polyoxometalate (PM523) was shown to be potent inhibitor of FluV A, respiratory
      syncytial virus and measles virus, and was shown to inhibit membrane fusion
      between FluV envelope and the cellular membrane. Strains of virus with acquired
      resistance to PM523 had mutations in the amino acids substrates in HA1 head, and
      amino acid changes occurred in the interface peptide of the trimers of HA. Cap
      formation of FluV-encoded mRNA is unique; it utilizes 5'-mGpppXm of host mRNA.
      Several substances which inhibit the cap formation of FluV (they are inhibitors
      of PB2 enzyme activity of FluV) are introduced and reviewed in this article. A
      metabolic product of ribavirn, 1,2,4 triazole carboxamide (T-CONH2) is inhibitory
      for FluV A growth in vitro. Peroral administration of TCONH2 also showed
      therapeutic effect in an experimental mouse infection model of FluV A as well as
      ribavirin. TCONH2 seems to be less toxic than ribavirin for mice, and may be
      useful as alternative chemotherapy of ribavirin. Other anti-FluV substances that
      have been reported to be effective for FluV infection in the mouse are discussed
      with respect to the possibility of their clinical potential.

PMID- 11594685
TI  - Inhibition of HIV infection by CXCR4 and CCR5 chemokine receptor antagonists.
AB  - The chemokine receptors CXCR4 and CCR5 are used as co-receptors by the T cell
      tropic (X4) and macrophage-tropic (R5) HIV-1 strains, respectively, for entering
      their host cells. Viral entry can be inhibited by the natural ligands for CXCR4,
      the CXC chemokine SDF-1 and CCR5, the CC chemokines RANTES, MIP-1alpha and MIP
      1beta. Several peptidic compounds, T22 (an 18-mer), T134 (a 14-mer), ALX40-4C (a
      9-mer) and CGP 64222 (also a 9-mer), have been identified as CXCR4 antagonists
      and show anti-HIV activity. Also, the HIV-1 tat protein has been described as a
      'natural' CXCR4 antagonist with anti-HIV-1 activity. The most potent and specific
      CXCR4 antagonists are the bicyclam derivatives, which also potently block X4 HIV
      replication. AMD3100 has proved to be a highly specific CXCR4 antagonist, which
      consistently blocks the outgrowth of all X4 HIV and dual-tropic (R5/X4) variants
      that use CXCR4 for entering the cells (cell lines, CXCR4-transfected cell lines,
      lymphocytes or monocytes/ macrophages). From the bicyclam analogues, AMD3100 was
      selected as the clinical drug candidate, which, after initial Phase I (safety)
      studies, has proceeded to Phase II (efficacy) trials. The first non-peptidic
      compound that interacts with CCR5, and not with CXCR4, is a quaternary ammonium
      derivative, called TAK-779, which also has potent but variable anti-HIV activity.
      We believe that HIV entry/fusion inhibitors will become important new antiviral
      agents to combat AIDS. However, like the current clinically approved agents, they
      will need to be used in combinations consisting of antivirals that target other
      aspects of the HIV replication cycle, such as reverse transcriptase and protease,
      to obtain optimum therapeutic effects.

PMID- 11594686
TI  - Spectrum of cdk-9 inhibitor activity against HIV-1 replication among various
      models of chronic and latent infection.
AB  - The cellular transcription elongation factor, P-TEFb, and its kinase component,
      cdk-9, have been implicated in the regulation of HIV-1 transactivation and
      transcription. We tested a panel of demonstrated cdk-9 kinase inhibitors for the
      ability to block HIV-1 expression in a variety of cell models representing
      chronic and latent/inducible infection. These agents induced cellular toxicity,
      in accordance with their potency for cdk-9 inhibition, with more pronounced
      toxicity in cultures of T-cell lineage. These agents also inhibited HIV-1
      expression, in accordance with their potency for cdk-9 inhibition, in several
      latent models tested (representing T-lymphocytic, promonocytic and promyelocytic
      lineages) and using various extracellular stimuli that activate HIV-1 expression
      via distinct intracellular pathways. Such was the case even though some of these
      cell models of latent/inducible HIV-1 infection harbour viral defects in the HIV
      1 transactivation mechanism. Two additional cell models of latent/inducible HIV-1
      infection, both derived from Jurkat T-lymphocytes, were relatively resistant to
      inhibition of viral expression by these agents. This apparent lack of effect was
      most likely due to the narrow therapeutic range of these agents in T-cell
      cultures. Inhibition of HIV-1 replication by these agents was also observed in
      two cell models representing constitutive viral expression in cells of T
      lymphocytic and promyelocytic lineages. Overall, the observed pattern of viral
      inhibition with these compounds suggests that cdk-9 enzymatic activity is
      important for HIV-1 expression irrespective of cell lineage or cellular pathway
      of viral activation. However, because of the non-selective nature of these
      inhibitors, other cellular pathways must also be considered. Agents that target
      cellular components essential for HIV-1 expression may provide new therapeutic
      approaches to limit viral replication, especially when combined with potent
      antiretroviral regimens.

PMID- 11594687
TI  - Structural studies of chemokines that inhibit HIV-1 entry.
AB  - The chemokine receptors CCR5 and CXCR4 have emerged as essential mediators of HIV
      1 pathophysiology, functioning as co-receptors for viral entry into cells. The
      physiological agonists of these receptors inhibit HIV-1 infection in vitro. The
      discovery of small molecules that disrupt the interactions between HIV-1 and
      chemokine receptors is one strategy to limit the spread of the virus. These
      compounds will complement already existing therapies that include HIV-1 reverse
      transcriptase and protease inhibitors. The complete structural elucidation of a
      chemokine ligand-receptor complex would be valuable for rational drug design, but
      has yet to be achieved. Structural studies of chemokine agonists and antagonists
      can also be useful in understanding interactions that may be important for drug
      optimization. This review examines the surface properties of the chemokine
      ligands human SDF-1alpha and HHV-8 vMIP-II, with a goal of determining receptor
      interacting sites. In combination with site-directed mutagenesis of the
      chemokines and structure-activity relationships of chemokine-based peptides, this
      approach will lead to a better understanding of the interactions in the chemokine
      ligand-receptor system.

PMID- 11594688
TI  - L-Nucleoside analogues against cancer-causing viruses have potential in the
      prevention, delayed onset and treatment of viral associated cancers.
AB  - It has been established that several types of cancers have a strong association
      with viruses. Thus, a potent antiviral compound without toxicity upon long-term
      usage will be useful not only for the treatment of viral diseases but also for
      the prevention or the delayed onset of those cancers that have a strong
      association with viruses. These compounds, depending upon their mechanism of
      action, could also potentially be useful for the treatment of those viral
      associated cancers. L(-)Deoxynucleoside analogues were discovered in my
      laboratory and by others as an important class of antiviral and anti-cancer
      chemical entities. L(-)SddC (3TC, lamivudine), L(-)FTC, L(-)Fd4C, and L(-)FMAU
      are compounds with potent activity against hepatitis B virus (HBV), but with
      different biological and pharmacological profiles. These compounds may be useful
      in the prevention or delayed onset of hepatocellular carcinoma associated with
      HBV. L(-)I-OddU is a potent anti-Epstein-Barr virus (EBV) compound without
      cytotoxicity and animal toxicity upon long-term dosing, which allows drug
      concentration in plasma that are much higher than those that are antivirally
      active. This compound may have the potential to prevent B-cell lymphoma
      associated with patients undergoing organ transplants in addition to its
      potential use for the treatment of EBV infection. Furthermore, it may also be
      useful for the treatment of EBV-associated cancers. In this manuscript, the
      metabolism, mechanism of action and the resistance, as well as the potential use
      of this class of compounds targetted against HBV, will be discussed.

PMID- 11594689
TI  - DABOs as candidates to prevent mucosal HIV transmission.
AB  - Worldwide, the heterosexual route is the prevalent mode of transmission of AIDS;
      therefore, demands have been raised for measures that block sexual spreading of
      the HIV infection. Development of microbicides for topical use may represent an
      efficacious alternative to condoms. Several approaches are being investigated.
      Besides surfactants, which directly act on the virus particle, and measures that
      enhance natural defence mechanisms, promising new candidates appear to be drugs
      that block the early steps of HIV multiplication. We describe herein a long-term
      assay which enables the establishment of whether the above drugs reversibly
      (virustatic action) or irreversibly (virucidal action) inhibit HIV-1
      multiplication, thus allowing screening for effective and potent microbicides. We
      validated our assay with nucleoside (NRTIs) and non-nucleoside reverse
      transcriptase inhibitors (NNRTIs). Following a chronic treatment, the NRTIs
      tested (didanosine, zalcitabine, stavudine and lamivudine) simply delayed the
      viral breakthrough with respect to infected, untreated controls. Under the same
      experimental conditions, non-nucleoside reveres transcriptase inhibitors
      (NNRTIs), such as MKC-442, alphaAPA, nevirapine, efavirenz and 3,4-dihydro-2
      alkoxy-6-benzyl-4-oxopyrimidines (DABOs) MC 1047 and MC 1220 suppressed HIV-1
      replication for the entire experimental period (40 days). When cell culture
      samples were evaluated for the presence of infectious virus, p24 antigen and
      viral DNA sequences, none of them was detected up to day 40 post-infection
      (p.i.). Identical results were obtained after a treatment with the above NNRTIs
      limited to the first 4 days p.i. Under more selective experimental conditions,
      that is drug treatments limited to the first 4 h p.i., nevirapine and efavirenz
      proved to be virustatic; in fact, viral breakthrough ensued shortly after their
      removal from the culture medium. Conversely, DABO MC 1220 was endowed with potent
      virucidal activity; in fact, at 3.5 microM it was able to suppress HIV-1
      multiplication in cultures acutely infected with a very high multiplicity of
      infection (5 CCID50/cell), thus allowing exponential cell multiplication as in
      uninfected cultures for the next 40 days.

PMID- 11594690
TI  - Early detection of mixed mutations selected by antiretroviral agents in HIV
      infected primary human lymphocytes.
AB  - A growing concern in the pursuit of new therapies for HIV-1 infection is the
      potential for the virus to develop drug resistance. With the advent of modern
      antiretroviral therapy and the common use of combined modalities, it is difficult
      to identify in the clinic the mutations associated with a specific drug. In
      general, drug selection of mutants using a relevant cell system, such as primary
      human lymphocytes, is a good prognosticator of what will happen in humans. In
      this study, HIV-infected human peripheral blood mononuclear cells were exposed,
      at a concentration of 1- to 10-fold the median effective antiviral concentration,
      to the nucleosides (-)-beta-2',3'-dideoxy-3'-thia-5-fluorocytidine [(-)-FTC] (-)
      beta-2',3'-dideoxy-3'-thiacytidine (3TC), 3'-azido-2',3'-dideoxyuridine (CS-87,
      AZDU), 3'-azido-2',3'-dideoxy-5-methylcytidine (CS-92, AZMC), 2',3'-didehydro-3'
      deoxythymidine (d4T), beta-L-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (beta
      L-D4FC), beta-L-2',3'-dideoxyadenine SATE[beta-L-ddAMP-bis(tbutylSATE)], beta-L-5
      fluoro-2',3'-dideoxycytidine (L-FddC), and the protease inhibitors nelfinavir and
      amprenavir (VX-478). Virus from the culture supernatant was amplified by PCR and
      analysed by both HIV-1 reverse transcriptase and protease line probe assay. All
      the L-nucleoside analogues tested selected for the V184 mutation, including the L
      pyrimidine nucleosides 3TC (-)-FTC, beta- L-FddC, beta-L-D4FC and the beta-L
      purine nucleoside. beta-L-D4FC also selected for K/R65 in addition to V184,
      indicating that these two mutations are linked and compatible in vitro. No
      pattern of mutations leading to resistance or reduced susceptibility was
      discerned with d4T. Rapid genotyping analysis revealed the different kinetics and
      mutations obtained by in vitro selection in HIV-infected cells exposed to
      nucleoside analogues and protease inhibitors.

PMID- 11594691
TI  - Impact of YMDD mutations during lamivudine therapy in patients with chronic
      hepatitis B.
AB  - Lamivudine is a nucleoside analogue with potent inhibitory effects on hepatitis B
      virus (HBV) replication. Prolonged therapy is required for sustained suppression.
      However, HBV species with mutations in the tyrosine-methionine-aspartate
      aspartate (YMDD) locus of the HBV RNA-dependent DNA polymerase conferring
      resistance to lamivudine may emerge after 9-10 months therapy with an incidence
      of 38 and 67% after 2 and 4 years of lamivudine therapy, respectively. During
      continued lamivudine therapy, patients with YMDD mutant HBV usually show serum
      alanine aminotransferase (ALT) and HBV DNA elevations at lower median levels than
      their baseline. Marked flare of serum ALT or acute exacerbation may occur as the
      result of CLT-mediated hepatocytolysis directed against YMDD mutants. Although
      viral clearance with or without emergence of distinct lamivudine-resistant
      mutants may occur after such exacerbations, 20% of the exacerbations are
      complicated with decompensation or even fatality. The exacerbations appear to be
      more severe than those that occur during the natural course of wild-type HBV
      chronic infection. In addition, some mutations may generate S gene truncation
      near 'transactivity-on-region'. Thus, the benefit of prolonged lamivudine therapy
      must be balanced against concern about YMDD mutants. Currently, the most cost
      effective strategy is to select patients with stronger endogenous anti-HBV
      immunity, thereby increasing efficacy and shortening the duration of lamivudine
      therapy. New drugs and new strategies are needed to better achieve the goals of
      therapy and minimize the problem of YMDD mutants.

PMID- 11594692
TI  - HIV/Hepatitis B and C co-infection: pathogenic interactions, natural history and
      therapy.
AB  - Recent advances in antiretroviral therapy for HIV infection have substantially
      improved overall mortality, as well as morbidity from life-threatening
      opportunistic infections. In place of the usual HIV-associated opportunistic
      infections, morbidity and mortality due to the sequelae of hepatitis B (HBV) and
      C virus (HCV) infections have taken on a leading role in HIV-infected
      individuals. This review will examine the pathogenesis of these viruses in the
      setting of co-infection and the effect of immunosuppression with HIV, the natural
      history of co-infection, with particular attention to the effect on serological
      and histological markers, and the effect of immune reconstitution on the course
      of HBV and HCV infection. Consideration will also be given to the effect of HIV
      infection on HBV and HCV load (especially for HCV) and progression of liver
      disease. Finally, we will discuss the rapidly evolving area of therapy, with
      particular attention to many of the newer agents now in clinical trials, as well
      as combinations of these agents.

PMID- 11594693
TI  - Advances in antiviral agents for hepatitis B virus.
AB  - Hepatitis B virus (HBV) is the third most common disease after venereal diseases
      and chickenpox. HBV currently infects 2 billion people in the world, of which 350
      million are chronic carriers. At least 1 million chronically infected individuals
      die each year due to HBV-related diseases, especially cirrhosis and liver cancer.
      The greatest concern about the diffusion of this virus is in endemic regions in
      central and southern Africa, South-East Asia and South America, where neonatal
      exposure results in high mortality rates. Anti-HBV therapy has made important
      progresses in the last decade, with two approved drugs and a number of other
      potent agents in the pharmaceutical industry pipeline. Nevertheless, resistance
      and viral rebound are still major issues in devising a winning strategy, and
      there is a continuous need of developing new active compounds, as well as
      therapeutic protocols based on combination therapy and a prophylactic approach.
      This review will summarize the latest advances in anti-HBV therapy, with
      particular regard to the latest clinical data on the most significant anti-HBV
      agents. Issues such as viral resistance and combination therapy will be
      highlighted.

PMID- 11594694
TI  - Building value-based partnerships: toward solidarity with oppressed groups.
AB  - We propose a value-based conceptualization of partnership, defining partnership
      as relationships between community psychologists, oppressed groups, and other
      stakeholders, which strive to achieve key community psychology values (caring,
      compassion, community, health, self-determination, participation, power-sharing,
      human diversity, and social justice). These values guide partnership work related
      to the development of services or supports, coalitions and social action, and
      community research and program evaluation. We prescribe guidelines for building
      such partnerships and conclude by considering some of the challenges in
      implementing value-based partnerships.

PMID- 11594695
TI  - Perceptions of parenting: individual differences and the effect of community.
AB  - Neighborhood norms are an important determinant of beliefs and attitudes about
      parenting, and measuring changes in community norms is an important component of
      evaluating community-based programs for improving child outcomes. The purpose of
      this study was to determine whether or not a survey of community residents'
      perceptions of parenting could be used to measure community parenting norms and
      whether these perceptions differed by individual or community characteristics.
      Two community surveys with 870 and 914 respondents, respectively, were conducted
      in 3 low-income neighborhoods. Results indicated that perceptions of parenting
      could be measured reliably at the community level although it is important to
      consider the presence of multiple norms when using such measures. Furthermore,
      differences in perceptions of parenting associated with individual
      characteristics were markedly decreased when neighborhood characteristics were
      considered, suggesting that the association of individual characteristics with
      perceptions of parenting is confounded by neighborhood characteristics.

PMID- 11594696
TI  - Correlates of employment among welfare recipients: do psychological
      characteristics and attitudes matter?
AB  - This study examines whether and how a wide range of potential barriers to work,
      including psychological characteristics and attitudes, are associated with
      current employment in a recent sample of welfare recipients in Michigan (N =
      672). Psychological factors include measures of depressive symptoms, work
      attitudes, and perceived risks associated with leaving welfare. Over and above
      demographic, economic, and contextual factors, positive psychological
      characteristics and attitudes were found to be moderately associated with
      currently being employed. Implications for welfare-to-work programs and policy
      are discussed.

PMID- 11594697
TI  - Searching for a normal life: personal accounts of adults with schizophrenia,
      their parents and well-siblings.
AB  - Using a life course perspective, the research examines personal accounts of
      adults with schizophrenia, and their parents and well-siblings from six families.
      Accounts of multiple members of the same family, including the family member with
      schizophrenia, are used to describe how families understand and accommodate life
      changes that result from the illness. Families describe the loss of a "normal
      life" as one of the most devastating aspects of schizophrenia. We present the
      personal and social losses described by adults with schizophrenia and their well
      family members, and document families' search for ways that their ill family
      member can achieve or maintain valued social roles. The concerns of well family
      members for the future of the ill family member and ways families contemplate
      transfer of care issues are described. Implications of the study for community
      research and action are discussed.

PMID- 11594698
TI  - Value-based praxis in community psychology: moving toward social justice and
      social action.
AB  - The purpose of this paper is to articulate a rationale for value-based praxis in
      community psychology. Although values need to promote personal, collective, and
      relational wellness at the same time, it is argued that community psychologists
      pay more attention to personal and relational wellness than to collective
      wellness. In order to address this imbalance it is important to promote the value
      of social justice. While praxis requires that we engage in a cycle of reflection,
      research, and social action, community psychologists devote more resources to the
      first two phases of praxis than to the last one. This paper offers a framework
      for deciding what values and what praxis considerations we should attend to and
      how we may advance social justice and social action in community psychology.

PMID- 11594699
TI  - Psychosocial outcomes of urban African American adolescents born to teenage
      mothers.
AB  - This is a study of psychosocial outcomes of adolescents born to teenage mothers.
      Adolescents'problem behaviors, psychological well-being, social support, school
      variables, and sexual behaviors are compared across three groups- those born to
      mothers 17 or younger, mothers 18-19 years old, and mothers 20 or older. Analyses
      from two samples of African American adolescents from Maryland (n = 205) and
      Michigan (n = 570) are reported. The results from both samples indicate that
      mother's age at birth is unrelated to adolescents' psychosocial outcomes. These
      two studies add to the limited number of analyses that examine adolescent
      outcomes for children of teen mothers. The results suggest that efforts to
      understand social structural determinants of healthy and problematic adolescent
      development may be more informative than examining the effects of mother's age.
      They also suggest that teen pregnancy prevention programs may be more effective
      if they are part of a larger prevention strategy that incorporates social
      structural change efforts and not only a focus on individual level change.

PMID- 11594700
TI  - Antioxidant status and lipid peroxidation in colorectal cancer.
AB  - Colon carcinogenesis is a multistep process where oxygen radicals were found to
      enhance carcinogenesis at all stages: initiation, promotion, and progression.
      Since insufficient capacity of protective antioxidant system can result in
      cancer, the aim of this study was to examine the activity of antioxidant enzymes
      (superoxide dismutase, catalase, glutathione peroxidase, and glutathione
      reductase) and the levels of reduced glutathione, vitamin C, and vitamin E. The
      lipid peroxidation products were also determined by measuring malondialdehyde and
      4-hydroxynonenal levels in colorectal cancer tissue collected from 55 patients.
      In these cases the activity of superoxide dismutase, glutathione peroxidase, and
      glutathione reductase was significantly increased while the activity of catalase
      was significantly decreased in cancer tissue. However, the level of nonenzymatic
      antioxidant parameters (glutathione, vitamin C, and vitamin E) was significantly
      decreased in cancer tissue. Further lipid peroxidation was enhanced during cancer
      development, manifested by a significant increase in malondialdehyde and 4
      hydroxynonenal levels. The obtained results indicate significant changes in
      antioxidant capacity of colorectal cancer tissues, which lead to enhanced action
      of oxygen radicals, resulting in lipid peroxidation.

PMID- 11594701
TI  - Gender-based profiles of developmental immunotoxicity to lead in the rat:
      assessment in juveniles and adults.
AB  - Gender-based differences in immunotoxicity induced by the heavy metal lead (Pb)
      have been observed both in the juvenile chicken and the adult rat following low
      level exposure during embryonic development. To better define the gender-based
      differences, as related to dose following in utero exposure to Pb, potential
      differential sensitivities were examined after exposure of F344 rats to low
      concentrations of Pb (0, 50, 100, or 250 ppm Pb) ad libitum throughout gestation.
      Immune assessment was performed in juveniles (5 wk old) and young adults (13 wk
      old). At the highest (250 ppm) Pb concentration examined, the delayed-type
      hypersensitivity (DTH) response was depressed in females relative to gender
      matched controls at both ages; relative spleen weights and relative neutrophil
      numbers were increased while relative and absolute monocyte numbers and relative
      basophil numbers were decreased at 13 but not 5 wk of age. In contrast, 250 ppm
      Pb-treated males did not differ in these endpoints. With in utero exposure to 100
      ppm Pb, 13-wk-old females again had decreased relative and absolute monocyte
      numbers and increased relative neutrophil numbers, although the DTH response was
      unchanged. Males (with 100 ppm Pb) had increased relative neutrophil numbers,
      decreased relative lymphocytes, and transiently increased nitrite production seen
      at 5, but not 13, wk of age. After gestational exposure to 50 ppm Pb, minimal
      immunotoxic effects were observed in either males or females at either
      developmental age assessed. These results suggest that differential gender-based
      immunotoxicity profiles exist after gestational Pb exposure depending on the
      concentration of Pb administered to the dam. In utero exposure of dams to 250 ppm
      Pb results in more profound immunotoxicity in females than males. Males arenot
      more sensitive to lower concentrations of Pb than females. Since the 50 ppm
      exposure produced minimal changes, these data may provide information to
      establish a no-observed-adverse-effect level (NOAEL) for in utero exposure to Pb.
      Additionally, while most effects were evident at both juvenile and adult ages,
      some changes were not fully evident until measured in the adult. Most changes
      were persistent with only one exception (male nitrite levels at 100 ppm).

PMID- 11594703
TI  - Embryonic exposure to low-dose pesticides: effects on growth rate in the
      hatchling red-eared slider turtle.
AB  - In the red-eared slider turtle, pesticides can alter expected sex outcomes, a
      major step in the inferred pathway of sex determination, and hatchling steroid
      physiology. Changes such as these can profoundly affect an organism's fitness.
      Other potential markers for effects on fitness include hatchling mass, hatchling
      use of maternal stores (residual yolk), and especially early hatchling growth
      rates. In the current study, red-eared slider turtles were exposed during
      embryogenesis to one of three compounds-chlordane, trans-Nonachlor, or p,p'-DDE
      all of which affect sex determination in this species. Turtles were weighed at
      hatching, after a 28-d fasting period, and after 14 d of ad libitum feeding. All
      three compounds had some population-wide effects on changes in mass from time
      point to time point when compared to controls. From hatching to the end of the 28
      d fast, turtles exposed in the egg to the mid-range doses of trans-Nonachlor and
      of p,p'-DDE lost mass and underwent a change in mass significantly different from
      controls. Additionally, turtles exposed to the two higher doses of trans
      Nonachlor and the mid-range dose of chlordane grew significantly more than
      controls after 14 d of ad libitum feeding. These results point to a role for
      pesticides in endocrine disruption that extends beyond sex determination and sex
      development.

PMID- 11594702
TI  - Gender differences in the potentiation of N-(3,5-dichlorophenyl)succinimide
      metabolite nephrotoxicity by phenobarbital.
AB  - The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) induces acute
      nephrotoxicity characterized as polyuric renal failure with proximal tubular
      necrosis. Phenobarbital pretreatment potentiates NDPS and N-(3,5-dichlorophenyl)
      2-hydroxysuccinimide (NDHS, a nephrotoxic metabolite of NDPS) nephrotoxicity in
      male rats. The purpose of this study was to determine the ability of
      phenobarbital pretreatment to potentiate (1) NDHS nephrotoxicity in female rats
      and (2) N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA, a nephrotoxic
      metabolite of NDHS) nephrotoxicity in male and female rats. Age-matched male and
      female Fischer 344 rats (4/group) were pretreated intraperitoneally (ip) with
      phenobarbital (75 mg/d, 3 d). At 24 h after the last injection of phenobarbital,
      an ip injection of NDHS (0.025 mmol/kg), 2-NDHSA (0.025 mmol/kg, females; 0.05
      mmol/kg, males), or vehicle was given and renal function was monitored at 24 and
      48 h post NDPS metabolite or vehicle. Additional groups received the NDPS
      metabolite or vehicle only and were also monitored for 48 h. In a separate
      experiment, male Fischer 344 rats were pretreated with piperonyl butoxide (PIBX,
      1360 mg/kg) or the PIBX vehicle. 2-NDHSA (0.1 mmol/kg) or vehicle was
      administered (ip) 30 min after PIBX, and renal function was monitored for 24 h.
      Phenobarbital markedly potentiated 2-NDHSA nephrotoxicity in male rats as
      evidenced by increased kidney weight, increased blood urea nitrogen (BUN)
      concentration, and decreased tetraethylammonium (TEA) accumulation by renal
      cortical slices. PIBX had no effect on 2-NDHSA nephrotoxicity. Phenobarbital
      pretreatment did not markedly enhance the nephrotoxic potential of NDHS or 2
      NDHSA in female rats. These results indicate that phenobarbital exhibits
      differential potentiation of NDPS metabolite nephrotoxicity in male and female
      rats and that the potentiation of 2-NDHSA nephrotoxicity observed in males is not
      due to cytochrome P-450-mediated oxidative biotransformation.

PMID- 11594704
TI  - Landfills, nocturnal foraging, and risk to aircraft.
AB  - Open landfills serve as an attractant to birds, with increasing risk of bird
      plane collisions. Managers are searching for methods to allow landfilling while
      reducing potential bird problems near airports. Some municipalities are
      considering nighttime landfilling as an avian deterrent, particularly where waste
      management facilities are located near airports. The objective of this report was
      to evaluate whether nighttime landfilling will result in increased risk to
      aircraft from birds at the Atlantic County Airport in coastal New Jersey. The
      risk to nearby aircraft from nighttime landfill is a function of (1)
      attractiveness of landfills, airports, or other habitats, (2) nocturnal behavior
      of gulls and other birds, (3) elevations and flight paths of birds, (4) changes
      in population levels of gulls and other potentially hazardous birds, and (5)
      harassment techniques that can deter birds from the landfills, adjacent habitat,
      and airports. The latter, however, can serve to move birds to locations or
      altitudes that pose an even greater risk to aircraft. The number of strikes is
      generally increasing. While most air strikes occur during the day at the Atlantic
      County Airport, over 12% occur at night and nearly 20% occur at dawn when any
      garbage remaining from nighttime landfilling would be an attractant. The peak of
      strikes occurs in the early fall, when young birds are learning to forage. Risk
      data suggests that gulls and a wide variety of other birds are active at night,
      and if any garbage is available they will be attracted, increasing the risk to
      aircraft landing at night. Some actual night dumping has been carried out since
      October 3 1997 without apparently attracting gulls, suggesting that careful
      operations with appropriate institutional controls can make nighttime dumping
      feasible.

PMID- 11594705
TI  - Transient loss of speech after removal of posterior fossa tumors--one aspect of a
      larger neuropsychological entity: the cerebellar cognitive affective syndrome.

PMID- 11594706
TI  - From Burkitt's lymphoma to chronic active Epstein-Barr virus (EBV) infection: an
      expanding spectrum of EBV-associated diseases.
AB  - Epstein-Barr virus (FBV) is one of 8 known human herpesviruses. EBV infection
      usually occurs in early childhood and is subclinical. However, primary infection
      in adolescence or adulthood causes infectious mononucleosis in approximately half
      of infected individuals. Recently, the spectrum of human diseases associated with
      EBV injection has increased, primarily due to methodological advances in EBV
      detection. Initially, EBV was isolated from a cultured Burkitt lymphoma cell
      line, and has been felt to be etiologically linked to the development of Burkitt
      lymphoma, as well as other human malignancies. This review mainly focuses on
      pathogenetic mechanisms, many of which remain enigmatic, for the various human
      diseases, which are considered to be associated with EBV injection.

PMID- 11594707
TI  - Is autologous bone marrow transplant (ABMT) and high-dose chemotherapy an
      approach that can rescue some children with advanced cancer disease?
AB  - The object was to determine the role ABMT in children with advanced cancer Those
      included had failed to respond to conventional treatment with 4 different
      ablative chemotherapy regimens. Bone marrow stem cells were identified with CD34.
      Cellular viability was determined after the bone marrow extraction and before the
      infusion. Fifteen patients were included, whose ages ranged from 1 to 13 years
      old with a median of 7. Six had acute leukemia, 6 with primitive neuroectodermic
      tumors, and 3 with other tumors. The median disease-free survival for the whole
      group was of 2 months, range of 1 to 29 months and SD of 10.1. A total of 6
      children are alive (40%) and without evidence of tumor activity from 1 to 29
      months. The disease-free survival rate for these group was of 19.1 months, with
      an SD of 7.9 months.

PMID- 11594708
TI  - Neonatal purpura fulminans due to homozygous protein C deficiency.
AB  - Severe and recurrent purpura fulminans developed in a Turkish boy at 1 week of
      age. Initial coagulation studies performed were compatible with disseminated
      intravascular coagulation. Subsequent investigations showed that the patient had
      homozygous and his healthy parents had heterozygous protein C deficiency. The
      episodes of purpura fulminans were controlled by infusions of fresh frozen plasma
      and heparinization. Oral anticoagulant therapy was given in the symptom-free
      period.

PMID- 11594709
TI  - Olfactory neuroblastoma as a second malignant neoplasm in a patient previously
      treated for childhood acute leukemia.
AB  - Various kinds of second malignant neoplasms after sucessful treatment for
      childhood acute leukemia have been reported. The authors describe an unusual case
      of an olfactory neuroblastoma in a patient previously treated for childhood acute
      leukemia including autologous bone marrow transplantation. The prophylactic
      cranial irradiation and the total body irradiation during autologous bone marrow
      transplantation may have induced the development of their patient's olfactory
      neuroblastoma. Although a second primary olfactory olfactory neuroblastoma is
      rare is rare, it should be added to the list of second malignant neoplasms in the
      sinonasal region.

PMID- 11594710
TI  - Osteosarcoma as a second malignancy after treatment for neuroblastoma.
AB  - A 4-month old girl was diagnosed as having stage IV neuroblastoma of the right
      adrenal gland. Preoperative chemotherapy was given, followed by local surgical
      excision. Postoperatively, irradiation of the tumor bed and adjuvant chemotherapy
      was given for 11 months. Nine years after cessation of chemotherapy, the patient
      developed left hip-joint pain. Biopsy of the ischium showed chondroblastic
      osteosarcoma. Limb salvage surgery was performed after preoperative chemotherapy.
      Postoperatively, adjuvant chemotherapy was given for 14 months. Twenty-two months
      after treatment for the secondary osteosarcoma, the patient has been remained in
      disease-free condition without any evidence of relapse. A second osteosarcoma
      occurring outside the radiation field after treatment for neuroblastoma is quite
      rare. This unusual case emphasized the need for close monitoring for development
      of second malignant neoplasms in survivors of neuroblastoma even in the absence
      of a known predisposing factor, such as radiation therapy.

PMID- 11594712
TI  - One day of serendipity and 10 years of work: the birth of the stethoscope.

PMID- 11594711
TI  - Radiotherapy in the management of Kasabach-Merritt syndrome: a case report.
AB  - A 21-day-old infant with hemangioma was brought to the hospital with enlargement
      of the hemangioma of the left thigh and purple discoloration around umbilicus.
      This led to the diagnosis of Kasabach-Merrill syndrome. Initial treatment with
      corticosteroid failed. The patient underwent radiotherapy that led successfully
      to improvement of both hemangioma and thrombocytopenia. After 2 years of follow
      up, the patient has experienced long-term complications, including atrophy and
      growth retardation of the irradiated leg.

PMID- 11594713
TI  - Guidelines of the German Society of Psychosomatic Obstetrics and Gynecology.

PMID- 11594714
TI  - Investigation into effectiveness of counseling on assisted reproductive
      techniques in Turkey.
AB  - This experimental study was conducted to determine the specific problems
      experienced by couples participating in assisted reproductive techniques (ART)
      and to assess couples' counseling needs. It was also intended to determine the
      effects of the counseling service model, developed and implemented by the
      researcher, on the success rate of ART, and to assess the couples' anxiety,
      depression and life satisfaction levels. Thirty couples for the experimental
      group and 30 couples for the control group were included in the study. The
      couples in the control group experienced the routine procedures that the
      treatment currently includes. Couples in the experimental group took part in the
      counseling service model, and were informed and supported throughout the steps of
      the ART A guide developed for the couples and education material developed for
      the counseling service model were used during the study. Three psychological
      tests were given to the couples before (pretest) and after (post-test) each
      procedure. These tests included anxiety, depression and life satisfaction
      inventories. The difference means test and Student's t test were used for
      statistical analysis. The results of the study showed that couples in the
      experimental group had lower anxiety and depression scores than the couples in
      the control group. Life satisfaction scores and pregnancy rates were higher for
      couples in the experimental group than for the couples in the control group.
      Statistical evaluation showed that the difference between the experimental group
      and the control group was significant (p < 0.05). This study demonstrates the
      importance of the counseling role of the nurse, and the development and
      application of counseling services in ART centers, in lowering the anxiety and
      depression levels of couples and ensuring success of the treatment.

PMID- 11594715
TI  - Subjective well-being in infertile couples.
AB  - The subjective well-being of infertile couples is affected by numerous variables.
      One hundred and ten infertile couples were investigated using the von Zerssen
      symptom checklist. With the exception of sterile women of fertile men (group 1:
      female infertility), women and men in the overall randomized sample and the
      diagnostic groups (group 2: subfertility of the man; group 3: sterility of both
      partners; group 4: idiopathic sterility) report fewer general symptoms than the
      overall population of patients with somatic and psychiatric diseases. Subfertile
      men show lower rating in the symptom checklist than the norm. Involuntarily
      childless women express more symptoms than their partners.

PMID- 11594716
TI  - 'Menopausal symptoms': associations with menopausal status and psychosocial
      factors.
AB  - This study investigated the relative importance of psychosocial factors as
      opposed to menopausal status in relation to so-called 'menopausal symptoms' among
      a large sample of premenopausal, perimenopausal and (naturally and surgically)
      postmenopausal women (n = 4308) in The Netherlands. The incidence of
      psychological, somatic, vasomotor and sexual symptoms was assessed and related to
      menopausal status and to measures relating to coping behaviors, (body- and self-)
      esteem and quality of life. Among the findings were that vasomotor symptoms in
      particular, and loss of interest in sex to a lesser extent, were relatively
      strongly associated with menopausal status. Psychological and somatic symptoms,
      however, were found to be more closely associated with psychosocial factors
      (although perimenopausal women as a group were found to suffer them most).
      Findings are discussed and interpreted as further evidence that only vasomotor
      symptoms may rightly be called 'menopausal'.

PMID- 11594717
TI  - Obstetricians and maternal body weight and eating disorders during pregnancy.
AB  - Intrauterine growth restriction (IUGR) is associated with maternal prepregnancy
      body mass index (BMI), body weight gain during pregnancy and smoking, eating and
      weight-losing behaviors. The aim of this pilot study was to examine the practices
      of obstetricians to determine whether more can be done to prevent IUGR and 'do no
      harm' to the body image of women during pregnancy. Obstetricians (n = 67) who
      reported delivering an average of 125 babies in the previous year completed a
      questionnaire that enquired about their antenatal practice of maternal weighing,
      history taking and referral of pregnant women. No doctor calculated the
      prepregnancy BMI. Women (90%) were weighed during some or all antenatal visits,
      usually by the nurse-receptionist, but one-third of the obstetricians did not
      refer to these body weight records. Most obstetricians asked women about their
      cigarette smoking and alcohol intake before pregnancy, and during pregnancy
      discussed supplements and nausea and vomiting. Fewer than 50% of doctors asked
      about depression, body weight control and disordered eating. One-third of doctors
      were not aware of having seen a woman with an eating disorder in the previous
      year. Obstetricians who asked about eating disorders were more likely to ask
      about depression, and obstetricians in private practice were significantly less
      likely to ask women about a history of depression and to refer women to a
      psychologist or psychiatrist Obstetricians could improve antenatal care by asking
      about body weight and calculating prepregnancy BMI, and investigating weight
      losing behavior and psychological or psychiatric problems such as eating
      disorders.

PMID- 11594718
TI  - Relationship between the NEO personality inventory revised neuroticism scale and
      prospectively reported negative affect across the menstrual cycle.
AB  - Previous research has suggested a possible link between neuroticism and
      premenstrual symptom changes. Results, however, are difficult to interpret given
      methodological problems such as retrospective reporting of premenstrual symptoms,
      and failure to control for the generalized influence of neuroticism on
      psychosomatic symptomatology. The present study aimed to address these issues.
      One hundred and nine women from the general population completed the modified
      Menstrual Distress Questionnaire daily for 70 days. Neuroticism was assessed
      using the NEO Personality Inventory Revised. Neuroticism accounted for a
      significant amount of variation in premenstrual negative affect both before and
      after controlling for baseline (follicular) symptom levels. The relationship
      between neuroticism and premenstrual negative affect could not be linked to any
      particular facet of neuroticism (e.g. anxiety, depression). Oral contraceptive
      (OC) users had significantly higher levels of neuroticism than the non-oral
      contraceptive (NOC) group. A significant interaction between OC use and menstrual
      cycle phase was also noted, with a trend toward OC users experiencing less
      premenstrual, but more menstrual, negative affect compared with the NOC group.
      The results are discussed in terms of the contribution of personality factors to
      the etiology of premenstrual change, and the utility of cognitive-behavioral
      treatment approaches.

PMID- 11594719
TI  - It's the gene, stupid!

PMID- 11594720
TI  - Emotional aspects of assisted reproductive medicine.

PMID- 11594721
TI  - New York City Department of Health response to terrorist attack, September 11,
      2001.
AB  - In response to two jet aircraft crashing into and causing the collapse of the 110
      storied World Trade Center (WTC) towers and the subsequent destruction of nearby
      portions of lower Manhattan, the New York City Department of Health (NYCDOH)
      immediately activated its emergency response protocol, including the mobilization
      of an Emergency Operations Center. Surveillance, clinical, environmental,
      sheltering, laboratory, management information systems, and operations were among
      the preestablished emergency committees. Because of its proximity to the WTC
      site, an emergency clinic was established at NYCDOH for triage and treatment of
      injured persons. NYCDOH focused its initial efforts on assessing the public
      health and medical impact of the attack and the resources needed to respond to it
      such as the care and management of large numbers of persons injured or killed by
      the crash; subsequent fire and building collapse; the health and safety of rescue
      workers; the environmental health risks (e.g., asbestos, smoke, dust, or chemical
      inhalation); other illnesses related to the disruption of the physical
      infrastructure (e.g., waterborne and foodborne diseases); and mental health
      concerns. Despite the evacuation and relocation of NYCDOH's headquarters, the
      department continued essential public health services, including death
      registration.

PMID- 11594722
TI  - Update: influenza activity--United States and worldwide, May-September 2001.
AB  - During October 2000-May 2001, influenza A (H1N1), A (H3N2), and B viruses were
      identified in the Northern Hemisphere. Influenza A (H1N1) and B viruses
      circulated widely; influenza A (H3N2) viruses were reported infrequently and were
      not associated with widespread outbreaks in any country during October 2000-May
      2001. Since May 2001, influenza A (H1N1) and B viruses have predominated in Asia
      and Oceania; influenza A (H3N2) and B viruses have predominated in Africa and
      South America. This report summarizes influenza activity in the United States*
      (1) and worldwide during May-September 25; influenza A (H1N1), A (H3N2), and B
      viruses continued to circulate worldwide and were associated with mild to
      moderate levels of activity. This activity underscores the need to follow the
      recommendations of the Advisory Committee on Immunization Practices (ACIP) (2,3)
      for the timely vaccination of persons at high risk for influenza-related
      complications.

PMID- 11594723
TI  - Progress toward poliomyelitis eradication--Angola, Democratic Republic of Congo,
      Ethiopia, and Nigeria, January 2000-July 2001.
AB  - In 1988, the World Health Assembly, governing body of the World Health
      Organization (WHO), resolved to eradicate poliomyelitis globally by 2000. In the
      African Region (AFR), WHO member countries began to implement polio eradication
      strategies in 1995. Although rapid progress has occurred in much of eastern and
      southern Africa, wild poliovirus transmission continues to occur in four priority
      countries: Angola, Democratic Republic of Congo (DR Congo), Ethiopia, and
      Nigeria. This report summarizes progress toward polio eradication in Angola, DR
      Congo, Ethiopia, and Nigeria during January 2000-July 2001, and indicates that 11
      of 12 cases of wild poliovirus in AFR were identified in these priority countries
      during January-July 2001.

PMID- 11594724
TI  - Strategies for reducing morbidity and mortality from diabetes through health-care
      system interventions and diabetes self-management education in community
      settings. A report on recommendations of the Task Force on Community Preventive
      Services.
AB  - Reducing morbidity and mortality and improving quality of life for persons with
      diabetes is an ongoing challenge for health-care providers and organizations and
      public health practitioners. Interventions are available that focus on persons
      with diabetes, health-care systems, families, and public policies. The Task Force
      on Community Preventive Services (the Task Force) has conducted systematic
      reviews of seven population-oriented interventions that can be implemented by
      health-care organizations and communities. Two of these interventions focus on
      health-care systems (disease and case management), and five focus on persons with
      diabetes (diabetes self-management education delivered in community settings). On
      the basis of these reviews, the Task Force has made recommendations regarding use
      of these seven interventions. The Task Force strongly recommends disease and case
      management in health-care systems for persons with diabetes. Diabetes self
      management education is recommended in community gathering places (e.g.,
      community centers or faith institutions) for adults and in the home for children
      and adolescents with type 1 diabetes. Evidence was insufficient to recommend
      diabetes self-management education interventions in other settings (i.e.,
      schools, work sites, and recreational camps) or in the home for adults with type
      2 diabetes. This report provides additional information regarding these
      recommendations, briefly describes how the reviews were conducted, provides
      sources of full reviews of interventions and information to assist in applying
      the interventions locally, and describes additional diabetes-related work in
      progress.

PMID- 11594725
TI  - Rapid purification and biochemical characterization of glucose kinase from
      Streptomyces peucetius var. caesius.
AB  - Glucose kinase catalyzes the ATP-dependent phosphorylation of glucose.
      Streptomyces peucetius var. caesius glucose kinase was purified 292-fold to
      homogeneity. The enzyme has cytosolic localization and is composed of four
      identical subunits, each of 31 kDa. The purified enzyme easily dissociates into
      dimers. However, in the presence of 100 mM glucose the enzyme maintains its
      tetrameric form. Maximum activity was found at 42 degrees C and pH 7.5.
      Isoelectric focusing of the enzyme showed a pl of 8.4. The N- and C-terminal
      amino acid sequences were MGLTIGVD and VYFAREPDPIM, respectively. The kinetic
      mechanism of S. peucetius var. caesius glucose kinase appears to be a rapid
      equilibrium ordered type, i.e., ordered addition of substrates to the enzyme,
      where the first substrate is d-glucose. The K(m) values for d-glucose and MgATP(2
      ) were 1.6 +/- 0.2 and 0.8 +/- 0.1 mM, respectively. Mg(2+) in excess of 10 mM
      inhibits enzyme activity.

PMID- 11594726
TI  - Rapid nongenomic effect of corticosterone on neuronal nicotinic acetylcholine
      receptor in PC12 cells.
AB  - The effects of corticosterone, a natural glucocorticoid of rat, on the
      acetylcholine (ACh)-induced current (I(ACh)) were studied in pheochromocytoma
      (PC12) cells by using whole-cell clamp technique. The I(ACh) proved to be
      generated through neuronal nicotinic receptor. ACh (30 microM) induced an inward
      current at a holding potential of -80 mV. When cells were preincubated with
      corticosterone (0.1-100 microM) for 4 min, an inhibitory effect of corticosterone
      on the peak of I(ACh) was found. This effect was reversible, concentration
      dependent, and voltage-independent. Intracellular application of corticosterone
      through the patch electrode did not affect the I(ACh). Extracellular application
      of 10 microM corticosterone neither shifted the dose-response curve of the peak
      I(ACh) to the right (dissociation constant (K(d)) = 16.5 microM) nor affected its
      coefficient (1.8) but inhibited the curve amplitudes by approximately 49% in the
      cells pretreated with corticosterone for 4 min. Bovine serum albumin-conjugated
      corticosterone (0.1-10 microM) had the inhibition similar to corticosterone. The
      inhibitor of transcription, actinomycin D (10 microM), and the protein synthesis
      inhibitor, cycloheximide (50 microM), had no effect on the inhibition induced by
      corticosterone on I(ACh). These results suggest that corticosterone has rapid
      inhibitory effect on I(ACh) in PC12 cells, which is mediated by a nongenomic
      mechanism. It indicates that corticosterone binds to the specific site on the
      outer cell membrane, probably on the neuronal nicotinic receptor-coupled channel,
      and inhibits the I(ACh) in a noncompetitive manner, thus controlling the
      immediate catecholamine release from the sympathetic cells.

PMID- 11594727
TI  - PFA, a novel mollusk agglutinin, is structurally related to the ribosome
      inactivating protein superfamily.
AB  - The structural organization of PFA, a novel beta-galactose-specific agglutinin
      from the snail Pomacea flagellata, was partially characterized. Using mass
      spectrometry, the molecular weight of this glycoprotein was determined as 32,444
      Da (7.4% carbohydrate). The agglutinin was found to form very large aggregates in
      solution, which were dissociated to monodisperse native-like dimers upon addition
      of polyethyleneglycol. The identity of the first 38 and the last 11 residues of
      the polypeptide chain was determined. It was found that PFA and the N-glycosidase
      subunit of ricin, a heterodimeric cytotoxin isolated from castor bean seeds, are
      homologous to each other in the N-terminal region. Furthermore, the far-UV
      circular dichroism spectra of these proteins were found to be nearly
      superimposable, evidencing that they share common general features in their
      secondary and tertiary structures. On the basis of these similarities, it can be
      concluded that PFA is structurally related to the ribosome-inactivating protein
      superfamily.

PMID- 11594728
TI  - Allosteric transition and substrate binding are entropy-driven in glucosamine-6
      phosphate deaminase from Escherichia coli.
AB  - Glucosamine-6P-deaminase (EC 3.5.99.6, formerly glucosamine-6-phosphate
      isomerase, EC 5.3.1.10) from Escherichia coli is an attractive experimental model
      for the study of allosteric transitions because it is both kinetically and
      structurally well-known, and follows rapid equilibrium random kinetics, so that
      the kinetic K(m) values are true thermodynamic equilibrium constants. The enzyme
      is a typical allosteric K-system activated by N-acetylglucosamine 6-P and
      displays an allosteric behavior that can be well described by the Monod-Wyman
      Changeux model. This thermodynamic study based on the temperature dependence of
      allosteric parameters derived from this model shows that substrate binding and
      allosteric transition are both entropy-driven processes in E. coli GlcN6P
      deaminase. The analysis of this result in the light of the crystallographic
      structure of the enzyme implicates the active-site lid as the structural motif
      that could contribute significantly to this entropic component of the allosteric
      transition because of the remarkable change in its crystallographic B factors.

PMID- 11594729
TI  - Electrostatic recognition between enzyme and inhibitor: interaction between
      papain and leupeptin.
AB  - Electrostatic forces are involved in a wide variety of molecular interactions
      that are of biological interest, including, among others, DNA-Protein
      interactions, protein folding, and the interactions between enzymes and their
      substrates and inhibitors. In this work, the interaction between papain and an
      inhibitor, leupeptin, is analyzed from the point of view of their electrostatic
      interaction. The computations enable one to suggest that negatively charged amino
      acids located in the region of the active site are responsible for creating an
      environment that enables efficient binding of the inhibitor. This binding occurs
      despite the fact that the net global charge of both molecules is positive; an
      explanation for this apparent contradiction is proposed.

PMID- 11594730
TI  - Evidence for peroxynitrite-mediated modifications to p53 in human gliomas:
      possible functional consequences.
AB  - Based on previous findings of increased nitric oxide synthase (NOS) expression in
      human gliomas (4), we hypothesized that peroxynitrite, a highly reactive
      metabolite of nitric oxide (NO) and superoxide (O(*-)(2)), might be increased in
      these tumors in vivo. Here we demonstrate that nitrotyrosine (a footprint of
      peroxynitrite protein modification) is present in human malignant gliomas.
      Furthermore, we show that p53, a key tumor suppressor protein, has evidence of
      peroxynitrite-mediated modifications in gliomas in vivo. Experiments in vitro
      demonstrate that peroxynitrite treatment of recombinant wild-type p53 at
      physiological concentrations results in formation of higher molecular weight
      aggregates, tyrosine nitration, and loss of specific DNA binding. Peroxynitrite
      treatment of human glioma cell lysates similarly resulted in selective tyrosine
      nitration of p53 and was also associated with loss of p53 DNA binding ability.
      These data indicate that tyrosine nitration of proteins occurs in human gliomas
      in vivo, that p53 may be a target of peroxynitrite in these tumors, and that
      physiological concentrations of peroxynitrite can result in a loss of p53 DNA
      binding ability in vitro. These findings raise the possibility that peroxynitrite
      may contribute to loss of wild-type p53 functional activity in gliomas by
      posttranslational protein modifications.

PMID- 11594731
TI  - Two distinct populations of tumor necrosis factor-stimulated gene-6 protein in
      the extracellular matrix of expanded mouse cumulus cell-oocyte complexes.
AB  - After the luteinizing hormone surge, the cumulus cell-oocyte complexes (COCs) in
      the preovulatory follicles produce a viscoelastic extracellular matrix, a process
      that requires the synthesis of hyaluronan as well as the incorporation of some
      components of the inter-alpha-trypsin inhibitor (IalphaI) family. In this study
      we report, that a hyaluronan-binding protein, the translated product of tumor
      necrosis factor-stimulated gene-6 (TSG-6), is also specifically accumulated in
      this matrix. TSG-6 mRNA expression is quickly upregulated and peaks at
      approximately 1500 copies/cell 4 h after the ovulatory stimuli as assessed by
      quantitative reverse transcription-polymerase chain reaction.
      Immunohistochemistry reveals the colocalization of the TSG-6 protein and
      hyaluronan around the cumulus and granulosa cells. The TSG-6 protein exists in
      two distinct populations in the COC matrix as demonstrated by Western-blot
      analysis. One population is a monomer that is anchored to the matrix by a
      noncovalent interaction. The second population is a covalent complex with either
      of the heavy chains of IalphaI and is bound to hyaluronan through a strong
      interaction that is resistant to denaturing conditions. The specific
      incorporation of the TSG-6 protein into the COC matrix suggests a structural role
      for this molecule.

PMID- 11594732
TI  - Nutritionally induced changes in the peroxisome proliferator-activated receptor
      alpha gene expression in liver of suckling rats are dependent on insulinaemia.
AB  - It was previously found that the expression of peroxisome proliferator-activated
      receptor-alpha (PPARalpha) was markedly augmented in the liver of suckling rats,
      in comparison to the fetuses and most notably to adult rats and it paralleled
      similar changes in hepatic lipid concentration. To determine whether these
      changes could be related to the high lipid content of the maternal milk and/or to
      hormonal status, the role of changes in nutrient availability and in plasma
      insulin concentration on liver expression during the perinatal stage in vivo in
      the rat was studied. When suckling rats were weaned on day 17, instead of on day
      20, the level of hepatic PPARalpha mRNA decreased earlier than in rats weaned
      later. When 10-day-old rats were force-fed with either glucose or Intralipid or a
      combination of both diets, it was found that, at similar low levels of plasma
      insulin, a high level of FFA stimulated PPARalpha expression, whereas, at similar
      high plasma FFA concentrations, an elevated insulin level attenuated the increase
      in PPARalpha expression. It is proposed that both the high lipid intake and
      decreased plasma insulin level are responsible for the high PPARalpha expression
      detected in rat neonates.

PMID- 11594733
TI  - Interaction of new sulfaphenazole derivatives with human liver cytochrome p450
      2Cs: structural determinants required for selective recognition by CYP 2C9 and
      for inhibition of human CYP 2Cs.
AB  - A series of new derivatives of sulfaphenazole (SPA), in which the NH(2) and
      phenyl substituents of SPA are replaced by various groups or in which the
      sulfonamide function of SPA is N-alkylated, were synthesized in order to further
      explore CYP 2C9 active site and to determine the structural factors explaining
      the selectivity of SPA for CYP 2C9 within the human P450 2C subfamily. Compounds
      in which the NH(2) group of SPA was replaced with R(1) = CH(3), Br, CH = CH(2),
      CH(2)CH = CH(2), and CH(2)CH(2)OH exhibited a high affinity for CYP 2C9, as shown
      by the dissociation constant of their CYP 2C9 complexes, K(s), which was
      determined by difference visible spectroscopy (K(s) between 0.1 and 0.4 microM)
      and their constant of CYP 2C9 inhibition (K(i) between 0.3 and 0.6 microM). This
      indicates that the CYP 2C9-iron(III)-NH(2)R bond previously described to exist in
      the CYP 2C9-SPA complex does not play a key role in the high affinity of SPA for
      CYP 2C9. Compounds in which the phenyl group of SPA was replaced with various
      aryl or alkyl R(2) substituents only exhibited a high affinity for CYP 2C9 if
      R(2) is a freely rotating and sufficiently electron-rich aryl substituent.
      Finally, compounds resulting from a N-alkylation of the SPA sulfonamide function
      (R(3) = CH(3), C(2)H(5), or C(3)H(7)) did not retain the selective inhibitory
      properties of SPA toward CYP 2C9. However, they are reasonably good inhibitors of
      CYP 2C8 and CYP 2C18 (IC(50) approximately 20 microM). These data allow one to
      better understand the structural factors that are important for selective binding
      in the CYP 2C9 active site. They also provide us with clues towards new selective
      inhibitors of CYP 2C8 and CYP 2C18.

PMID- 11594734
TI  - Expression of an isoform of the testis-specific estrogen sulfotransferase in the
      murine placenta during the late gestational period.
AB  - Cytosolic sulfotransferases play essential roles in regulating the activities and
      transfer of steroids. To evaluate their biological significance in the murine
      uterus and placenta during the course of gestation, we determined their
      activities with several steroids as substrates. Activated estrogen
      sulfotransferase (EST) was found in the placenta and uterus during the late
      gestational period. Reverse-transcribed cDNA of murine placental EST (mpEST) was
      isolated from mouse placenta at 18 days of gestation and its expression in the
      tissue coincided with a change in its enzyme activity. The open-reading frame of
      mpEST encodes a protein composed of 296 amino acids with a predicted molecular
      mass of 35.5 kDa and was revealed to be an isoform of the murine testis-specific
      EST gene (99.7%). Also, the amino acid sequence of mpEST showed 49.6 and 77.9%
      homology with human placental and endometrial EST, respectively, showing that it
      corresponds to human endometrial EST. COS-7 cells transfected with mpEST
      exhibited sulfotransferase activity with the phenolic hydroxy groups of steroids
      and artificial substrates. The best acceptor substrate was estrogen.

PMID- 11594735
TI  - Restoration of decreased N-methyl-d-asparate receptor activity by brain-derived
      neurotrophic factor in the cultured hippocampal neurons: involvement of cAMP.
AB  - Brain-derived neurotrophic factor (BDNF) may play an important role in the
      modulation of N-methyl-d-asparate (NMDA) receptor function. To elucidate the
      underlying mechanisms, whole-cell patch-clamp recording was used to assess the
      effect of BDNF on the responses of cultured hippocampal neurons to the glutamate
      receptor agonist NMDA. We found that peak amplitude of NMDA-evoked currents in
      cultured hippocampal pyramidal neurons at Day 18 in vitro decreased significantly
      compared to that of NMDA currents at Day 10 or 14. Interestingly, NMDA-evoked
      currents were greatly enhanced by BDNF (50 ng/ml) in cultured neurons at Day 18,
      but not at Day 10 or 14. Treatment with Rp-cAMP abolished the potentiating
      effects of BDNF on NMDA current. Elevating the amount of cytosolic cAMP by
      preincubation with forskolin or Sp-cAMP also enhanced NMDA currents as
      effectively as BDNF in 18-day-old hippocampal neurons. Measurement of the
      cellular content of cAMP by RIA indicated that cultured hippocampal neurons
      showed decreased basal cAMP levels at the time NMDA currents were decreased and
      BDNF increased the decreased cAMP levels. Taken together, these results suggest
      that BDNF may restore decreased NMDA receptor activity in cultured hippocampal
      neurons by the cAMP pathway.

PMID- 11594736
TI  - Inactivation of glutathione S-transferases by nitric oxide-derived oxidants:
      exploring a role for tyrosine nitration.
AB  - Reactive intermediates derived from nitric oxide ((*)NO) are thought to play a
      contributing role in disease states associated with inflammation and infection.
      We show here that glutathione S-transferases (GSTs), principal enzymes
      responsible for detoxification of endogenous and exogenous electrophiles, are
      susceptible to inactivation by reactive nitrogen species (RNS). Treatment of
      isolated GSTs or rat liver homogenates with either peroxynitrite, the
      myeloperoxidase/hydrogen peroxide/nitrite system, or tetranitromethane, resulted
      in loss of GST activity with a concomitant increase in the formation of protein
      associated 3-nitrotyrosine (NO(2)Tyr). This inactivation was only partially
      (<25%) reversible by dithiothreitol, and exposure of GSTs to hydrogen peroxide or
      S-nitrosoglutathione was only partially inhibitory (<25%) and did not result in
      protein nitration. Thus, irreversible modifications such as tyrosine nitration
      may have contributed to GST inactivation by RNS. Since all GSTs contain a
      critical, highly conserved, active-site tyrosine residue, we postulated that this
      Tyr residue might present a primary target for nitration by RNS, thus leading to
      enzyme inactivation. To directly investigate this possibility, we analyzed
      purified mouse liver GST-mu, following nitration by several RNS, by trypsin
      digestion, HPLC separation, and matrix-assisted laser desorption/ionization-time
      of flight analysis, to determine the degree of tyrosine nitration of individual
      Tyr residues. Indeed, nitration was found to occur preferentially on several
      tyrosine residues located in and around the GST active site. However, RNS
      concentrations that resulted in near complete GST inactivation only caused up to
      25% nitration of even preferentially targeted tyrosine residues. Hence, nitration
      of active-site tyrosine residues may contribute to GST inactivation by RNS, but
      is unlikely to fully account for enzyme inactivation. Overall, our studies
      illustrate a potential mechanism by which RNS may promote (oxidative) injury by
      environmental pollutants in association with inflammation.

PMID- 11594737
TI  - Green fluorescent protein rendered susceptible to proteolysis: positions for
      protease-sensitive insertions.
AB  - The green fluorescent protein (GFP) is highly resistant to proteolysis and
      remains uncleaved after prolonged incubation with trypsin or pronase despite
      several putative tryptic and chymotryptic sites in exposed loops. We have
      rendered GFP sensitive to proteolysis by inserting five amino acids, IEGRS, in
      loops at position 157, 172, or 189. Excitation and emission maxima of the three
      insertion mutants were similar to those of wild type, but quantum yields of
      mutants Omega172 and Omega189 were lower, indicating increased freedom of the
      fluorophore. Trypsin cleaved the native (folded) form of each mutant at a unique
      site defined by the insert. Pronase also yields similar digestion patterns in
      these variants, but further proteolysis was also observed, suggesting that the
      primary cleavage relaxes GFP structure and reveals previously inaccessible sites.
      Fluorescence of Omega189 changed little upon digestion with trypsin but decreased
      progressively by as much as 40% upon digestion with increasing amounts of
      pronase. Fluorescence of other variants was not affected significantly by the
      proteases, further confirming the remarkable stabilities of GFP variants. These
      constructs define a new conformation-sensitive site around residue 189 of GFP and
      show that GFP may be useful for design of protease-susceptible molecules for
      monitoring of specific proteolytic activities in vivo.

PMID- 11594738
TI  - Purification, sequencing, and phylogenetic analyses of novel Lys-49
      phospholipases A(2) from the venoms of rattlesnakes and other pit vipers.
AB  - Basic phospholipase A(2) homologs with Lys49 substitution at the essential Ca(2+)
      binding site are present in the venom of pit vipers under many genera. However,
      they have not been found in rattlesnake venoms before. We have now screened for
      this protein in the venom of rattlesnakes and other less studied pit vipers. By
      gel filtration chromatography and RP-HPLC, Lys49-phospholipase-like proteins were
      purified from the venoms of two rattlers, Crotalus atrox and Crotalus m.
      molossus, and five nonrattlers, Porthidium nummifer, Porthidium godmani,
      Bothriechis schlegelii, Trimeresurus puniceus, and Trimeresurus albolabris. Their
      N-terminal amino acid sequences were shown to be characteristic for this
      phospholipase subfamily. The purified basic proteins from rattlesnakes caused
      myonecrosis and edema in experimental animals. We have also cloned the cDNAs and
      solved the complete sequences of four novel Lys49-phospholipases from the venom
      glands of C. atrox, P. godmani, B. schlegelii, and Deinagkistrodon acutus
      (hundred-pace). Phylogenetic analyses based on the amino acid sequences of 28
      Lys49-phospholipases separate the pitviper of the New World from those of the Old
      World, and the arboreal Asiatic species from the terrestrial Asiatic species. The
      implications of the phylogeny tree to the systematics of pit vipers, and
      structure-function relationship of the Lys49-phospholipases are discussed.

PMID- 11594739
TI  - Purification and characterization of benzoate-para-hydroxylase, a cytochrome P450
      (CYP53A1), from Aspergillus niger.
AB  - Benzoate-para-hydroxylase (CYP51A or BpH) and NADPH:cytochrome P450 reductase
      from the filamentous fungus Aspergillus niger were purified to apparent
      homogeneity, using an overproducing A. niger strain. This is the first membrane
      bound fungal cytochrome P450 to be isolated and characterized. Combining BpH with
      NADPH:cytochrome P450 oxidoreductase in the presence of the phospholipid dilauryl
      phosphatidylcholine restored the BpH activity, although to only a minor extent.
      Spectral analysis of BpH showed characteristic spectra for a cytochrome P450.
      Substrate binding studies with purified BpH as a function of temperature and as a
      function of pH were performed. Temperature-dependent studies, at pH 8.0, showed
      that the simplified spin equilibrium model originally proposed for camphor
      binding to cytochrome P450cam (M. T. Fisher and S. G. Sligar, 1987, Biochemistry
      26, 4797-4803) also applies to the benzoate-BpH system. Two equilibrium constants
      were determined, K(1) for substrate binding without a spin change and K(2) for
      the spin change of the benzoate-BpH complex. pH-dependent binding studies showed
      that both K(1) and K(2) increase with pH, indicative of a higher affinity. As
      K(1) decreases more strongly with pH than K(2), we suggest that benzoate first
      binds to a binding site on the outside of the protein in a pH-dependent way,
      followed by transfer to the inside of the protein causing a spin change at the
      heme iron. The strong pH dependence of K(1) could be the result of the need to
      break salt bridges at the binding site on the outside of the protein. pH
      dependent kinetic studies with microsomes showed that the apparent K(M) values
      followed the trend observed for benzoate binding to purified BpH, while k(cat)
      values were virtually constant between pH 6.6 and 8.0 and decreased above pH 8,
      probably due to loss of productive interaction between BpH and NADPH:cytochrome
      P450 oxidoreductase. Research into the substrate specificity of BpH showed that
      BpH can only use benzoic acid and some of its derivatives. Monosubstitution on
      the phenyl ring is allowed but only at certain positions with specific, not too
      large groups. Substitution always leads to a lower affinity of the substrate.
      With one exception, all substrates were converted to their 4-hydroxy derivative.
      The exception, 3-methoxybenzoate, was demethylated to yield 3-hydroxybenzoate
      only. The restricted number of substrates and the specificity in catalysis
      suggest that BpH is not a general-purpose hydroxylase but that its role is
      confined to benzoate hydroxylation in the beta-ketoadipate pathway of A. niger.

PMID- 11594740
TI  - Activity profile of glutathione-dependent enzymes and respiratory chain complexes
      in rats supplemented with antioxidants and treated with carcinogens.
AB  - Appropriate dietary interventions may reduce the potentially damaging effects of
      free radicals generated during metabolism and various physiological conditions.
      We have investigated the effects of dietary vitamins C, E, beta-carotene, or
      selenium (Se) on the activity of endogenous antioxidant enzymes and respiratory
      chain complexes in rats exposed to 7,12-dimethylbenz[a]anthracene (DMBA), a
      mammary carcinogen and bleomycin (BLM), an antineoplastic drug. These agents are
      known to generate DNA-reactive species during their metabolism, which may enhance
      oxidative stress in cells. Female Fischer 344 rats aged 4 months were given
      antioxidant supplements singly or as a mixture 2 weeks prior to mutagen
      treatments; antioxidant supplementation continued for an additional 4 weeks. In
      rats treated with mutagens, the antioxidant intake lowered the activity of Se
      dependent glutathione peroxidase (Se-GPx) in liver cytosolic and mitochondrial
      fractions, compared to activity in rats treated with mutagens alone. However, the
      vitamins, but not Se supplement, persistently increased Se-GPx activity in
      untreated control animals. Treatment of animals with mutagen raised K(m) value of
      Se-GPx and this correlated with an increase in V(max). However, Se intake, either
      singly or mixture, significantly reduced K(m) value in mutagen-treated and
      untreated rats in both fractions. Se intake increased glutathione S-transferases
      (GST) activity (P < 0.05) in both liver fractions of mutagen-treated and
      untreated animals. Similar response was seen in Se-independent GPx. Since GST
      alpha possesses Se-independent GPx activity, the enhanced effect observed in GST
      activity may be due, in part, to increased activity in Se-independent GPx. Also,
      selenium or the antioxidant vitamin supplementation increased the activity of all
      four respiratory chain complexes in untreated rats. Although BLM treatment
      significantly increased the activity of electron transport complexes III and IV,
      selenium or the vitamin supplements modulated the responses. These results
      indicate that the intake of dietary vitamins or Se enhances antioxidant capacity
      in chemically exposed animals compared to animals receiving antioxidants alone.
      Furthermore, in addition to being an enhancer of the catalytic function of
      glutathione peroxidase, selenium may directly play a role as an antioxidant.

PMID- 11594741
TI  - Sensitivity of Deinococcus radiodurans to gamma-irradiation: a novel approach by
      Fourier transform infrared spectroscopy.
AB  - Deinococcus radiodurans is a red-pigmented coccus known to be particularly
      resistant to both chemical and radiative agents. Fourier transform infrared (FT
      IR) spectroscopy was used as a convenient and easy-to-run method to monitor
      damage induced in this bacterium by ionizing radiations. First, stationary-phase
      cultures were submitted to increasing doses of gamma-irradiation ((137)Cs
      source). Beyond a threshold of 11 kGy, striking changes occurred in spectra of
      irradiated samples compared with unirradiated ones, especially in the 1750-900
      cm(-1) region, which is spectroscopically assigned to amide I and II components,
      nucleotide bases, the phosphodiester backbone, and the sugar ring. Second,
      bacterial cultures were postirradiation reincubated. After a reincubation time of
      15 h, the oxidative stress was in part overwhelmed, and the growth of D.
      radiodurans again occurred, although some biocellular components remained
      altered. Consequently, FT-IR analysis is an accurate means to rapidly visualize
      biomolecular changes undergone by cells both after gamma-irradiation and during
      the repair mechanism.

PMID- 11594742
TI  - Rotary catalysis within ATP synthases: a bioinformatic approach provides novel
      insight into how large pH-dependent movements of the C-terminal helix of subunit
      c may be accommodated.

PMID- 11594743
TI  - Dual effects of ionic strength on Klebsiella aerogenes urease: pH-dependent
      activation and inhibition.

PMID- 11594744
TI  - The roles of PDZ-containing proteins in PLC-beta-mediated signaling.
AB  - Mammalian phospholipase C-beta isozymes are activated by a heterotrimeric GTP
      binding protein linked to various cell surface receptors. Recent reports suggest
      that PDZ domain proteins play a significant role of PDZ-containing proteins in
      the regulation of mammalian PLC-beta isozymes. PDZ-containing proteins mediate
      the clustering of receptors and signaling molecules and thereby regulate agonist
      induced signal transduction in polarized cells such as neuronal and epithelial
      cells. NORPA, a Drosophila PLC-beta, is known to be a component of a signaling
      complex that includes TRP and rhodopsin through interaction with INAD, a PDZ
      containing protein. Mammalian PLC-beta1 and -beta2 isoforms interact with a PDZ
      containing protein NHERF which is coupled to Trp4, a Ca(2+) channel. In addition,
      PLC-beta3 specifically interacts with E3KARP, another protein closely related to
      NHERF, through its C-terminal PDZ-binding motif. E3KARP up-regulates the PLC
      beta3 activation coupled to muscarinic receptor. In this review, the role of
      signaling complexes mediated by PDZ-containing proteins in the regulation of PLC
      beta isoforms will be discussed.

PMID- 11594745
TI  - Constitutive activation of Wnt/beta-catenin signaling pathway in migration-active
      melanoma cells: role of LEF-1 in melanoma with increased metastatic potential.
AB  - A constitutive complex of beta-catenin and LEF-1 has been detected in melanoma
      cell lines expressing either mutant beta-catenin or mutant APC (Rubinfeld et al.,
      Science, 275, 1790-1792, 1997). However, it has been recently reported that beta
      catenin mutations are rare in primary malignant melanoma, but its nuclear and/or
      cytoplasmic localization, a potential indicator of Wnt/beta-catenin pathway
      activation, is frequently observed in melanoma (Rimm et al., Am. J. Pathol., 154,
      325-329, 1999). In human malignant melanoma, the appearance of the tumorigenic
      phase represents a capacity for metastasis and is the significant phenotypic step
      in disease progression. Cell motility in invasive melanoma is thought to play a
      crucial role in metastatic behavior. In this work, we sought to determine which
      transcription factor of the LEF/TCF family was preferentially involved in human
      melanoma from different stages of tumor progression. We show that LEF-1 mRNA
      expression is predominant in highly migrating cells from metastatic melanomas.
      These actively migrating melanoma cells showed nuclear and cytoplasmic
      accumulation of beta-catenin and active transcription from a reporter plasmid of
      the LEF/TCF binding site. These results may provide a new insight into the role
      of the Wnt/beta-catenin signaling pathway in the tumor progression of malignant
      melanoma.

PMID- 11594746
TI  - U86, a novel snoRNA with an unprecedented gene organization in yeast.
AB  - The Xenopus laevis Nop56 gene (XNOP56), coding for a snoRNP-specific factor,
      belongs to the 5'-TOP gene family. XNOP56, as many 5'-TOP genes, contains an
      intron-encoded snoRNA. This previously unidentified RNA, named U86, was found as
      a highly conserved species in yeast and human. While in human it is also encoded
      in an intron of the hNop56 gene, in yeast it has an unprecedented gene
      organization: it is encoded inside an open-reading frame. Both in X. laevis and
      yeast, the synthesis of U86 snoRNA appears to be alternative to that of the
      cotranscribed mRNA. Despite the overall homology, the three U86 snoRNAs do not
      show strong conservation of the sequence upstream from the box D and none of them
      displays significant sequence complementarity to rRNA or snRNA sequences,
      suggesting a role different from that of methylation.

PMID- 11594747
TI  - Molecular cloning and characterization of the mouse E2F6 gene.
AB  - E2F6 is the most recently identified member of the E2F family. In this study, the
      murine E2F6 gene was cloned and found to consist of eight exons. Analysis of its
      5' flanking region revealed two transcription start sites. The proximal promoter
      region contained no TATA or CAAT box. We also identified a novel E2F6 mRNA
      containing the alternative exon 2. The E2F6 mRNAs are highly expressed during
      mouse embryogenesis and are present in all adult tissues examined. Moreover, E2F6
      shows a unique expression pattern in synchronized mouse embryonic fibroblasts.
      E2F6 expression rapidly increases during the G0-G1 transition, reaching its
      higher level in mid-G1, and remains relatively constant thereafter. These
      findings suggest that E2F6 may contribute to the regulation of events throughout
      the cell cycle. Isolation of the murine E2F6 gene is a step toward generation of
      genetically modified mouse models that will help to understand the functions of
      E2F6.

PMID- 11594748
TI  - PKCdelta and zeta mediate IL-4/IL-13-induced germline epsilon transcription in
      human B cells: a putative regulation via PU.1 phosphorylation.
AB  - We have investigated the role of PKC isozymes in the function of IL-4 and IL-13
      in human B cells. In a Burkitt's B lymphoma cell line, DND39, IL-4 induced the
      translocation of PKCdelta and zeta from the cytosol to the membrane fraction. The
      activation of germline epsilon promoter by IL-4 was abrogated not only by the
      expression of dominant negative mutants of PKCdelta and zeta but also by isozyme
      selective PKC inhibitors, rottlerin and PKCzeta pseudosubstrate peptide. These
      inhibitors also suppressed IL-4/IL-13-induced germline epsilon transcription in
      the IL-13Ralpha1-transfected DND39 cells as well as in normal human B cells, but
      had no influence on the induction of CD23b in the latter cells. As a downstream
      event of PKC, we found threonine phosphorylation of PU.1 in IL-4-stimulated DND39
      cells. This phosphorylation was suppressed by the PKC inhibitors, although STAT6
      activation was unaffected. These results suggest that, in human B cells, IL-4/IL
      13 utilize PKCdelta and zeta for the STAT6-independent signaling pathway and
      thereby modulate the transcriptional activity of PU.1.

PMID- 11594749
TI  - IL-1beta down-regulates tissue-type plasminogen activator by up-regulating low
      density lipoprotein receptor-related protein in AML 12 cells.
AB  - Interleukin-1 (IL-1) regulation of tPA in hepatocytes was studied in mouse
      hepatocyte line AML12. IL-1 induced transient accumulation of tPA mRNA as high as
      threefold by 2 h after the start of treatment. The cytokine also induced the mRNA
      for serum amyloid A, a typical acute-phase protein in mice, with more sustained
      kinetics in a time-dependent manner. In contrast to the induction of mRNA, tPA
      activity and protein levels in the harvested medium were dramatically diminished
      by IL-1. IL-1 stimulated the uptake of (125)I-tPA by AML 12. This uptake was
      inhibited by 39-kDa receptor-associated protein (RAP), but not by the sugar
      mannan. These results revealed that low-density lipoprotein receptor-related
      protein (LRP), which is known to be a receptor for tPA and to be blocked by RAP,
      was up-regulated by IL-1. We also demonstrated, for the first time, that IL-1
      transiently increased the mRNA level of LRP threefold by 30 min after the start
      of IL-1 treatment of AML 12. The receptor-mediated endocytosis of tPA by
      hepatocytes may thus play a crucial role in the down-regulation of fibrinolysis
      during the acute-phase response.

PMID- 11594750
TI  - Nitric oxide and tumor necrosis factor-alpha production by oleanolic acid via
      nuclear factor-kappaB activation in macrophages.
AB  - Oleanolic acid (OA), a pentacyclic triterpene acid, is reported to have antitumor
      activities; however, the mechanism underlying its antitumorigenic effects is
      poorly understood. To further determine the mechanism of OA, we investigated the
      effects of OA on the release of nitric oxide (NO) and tumor necrosis factor-alpha
      (TNF-alpha) and on the level of inducible nitric oxide synthase (iNOS) and TNF
      alpha gene expression in mouse macrophages. We found that OA elicited a dose
      dependent increase in NO and TNF-alpha production. Reverse transcription
      polymerase chain reaction showed that the increased NO and TNF-alpha secretion
      were due to an increase in iNOS mRNA and TNF-alpha mRNA, respectively. Since iNOS
      and TNF-alpha transcription have recently been shown to be under the control of
      the NF-kappaB transcription factor, the effects of OA on NF-kappaB activation
      were examined using a transient transfection assay and an electrophoretic
      mobility shift assay (EMSA). Transient expression assays with NF-kappaB binding
      sites linked to the luciferase gene revealed that the increased levels of iNOS
      mRNA and TNF-alpha mRNA induced by OA were mediated by the NF-kappaB
      transcription factor complex. Using DNA fragments containing the NF-kappaB
      binding sequence, OA was shown to activate the protein/DNA binding of NF-kappaB
      to its cognate site as measured by EMSA. These results demonstrate that OA
      stimulates NO and TNF-alpha release and is able to upregulate iNOS and TNF-alpha
      expression through NF-kappaB transactivation, which may be the mechanism whereby
      OA elicits its biological effects.

PMID- 11594751
TI  - The role of the coiled-coil motif in interactions mediated by TPD52.
AB  - TPD52 (D52)-like proteins are small coiled-coil motif-bearing proteins first
      identified through their expression in human breast carcinoma that mutually
      interact in hetero- and homomeric fashions. However, it has been unclear whether
      the coiled-coil motif is sufficient, or even necessary, for these interactions to
      occur. We have therefore examined the binding activities of a panel of C
      terminally deleted D52 proteins in both the yeast two-hybrid system and pull-down
      assays. In the yeast two-hybrid system, interactions were only detected when
      regions C-terminal to the coiled-coil motif were also present. However, using
      pull-down assays, interactions were detected for all deletion mutants which
      included the coiled-coil motif. This suggests that the coiled-coil motif is
      indeed necessary for interactions mediated by D52 proteins, but that C-terminal
      protein regions facilitate and/or stabilize these interactions.

PMID- 11594752
TI  - Development and characterization of an antisense-mediated prepackaging cell line
      for adeno-associated virus vector production.
AB  - One of the limitations of recombinant adeno-associated virus (rAAV) vector
      systems for gene therapy applications has been the difficulty in producing the
      vector in sufficient quantity for adequate evaluation. Since the AAV Rep proteins
      are cytotoxic, it is not easy to establish stable cell lines that express them
      constitutively. We describe a novel 293-derived prepackaging cell line which
      constitutively expresses the antisense rep/cap driven by a loxP-flanked CMV
      promoter. This cell line was converted into a packaging cell line expressing
      Rep/Cap for rAAV vector production through adenovirus-mediated introduction of a
      Cre recombinase gene. Without the introduction of the Cre recombinase gene, the
      cell line was shown to produce neither Rep nor Cap. rAAV vector was produced (1 x
      10(9) genome copies/3.5-cm dish) 4 days after the transduction with Cre
      expression adenovirus vector together with transfection of AAV vector plasmid. We
      further showed that the addition of Cap-expression adenovirus vector caused a 10
      fold increase in the yield of rAAV vector. This system is also capable of
      producing rAAV as a transfection-free system by using a small amount of rAAV
      instead of vector plasmid.

PMID- 11594753
TI  - Structural and functional characterization of human NAD kinase.
AB  - NADP is essential for biosynthetic pathways, energy, and signal transduction. Its
      synthesis is catalyzed by NAD kinase. Very little is known about the structure,
      function, and regulation of this enzyme from multicellular organisms. We
      identified a human NAD kinase cDNA and the corresponding gene using available
      database information. A cDNA was amplified from a human fibroblast cDNA library
      and functionally overexpressed in Escherichia coli. The obtained cDNA, slightly
      different from that deposited in the database, encodes a protein of 49 kDa. The
      gene is expressed in most human tissues, but not in skeletal muscle. Human NAD
      kinase differs considerably from that of prokaryotes by subunit molecular mass
      (49 kDa vs 30-35 kDa). The catalytically active homotetramer is highly selective
      for its substrates, NAD and ATP. It did not phosphorylate the nicotinic acid
      derivative of NAD (NAAD) suggesting that the potent calcium-mobilizing pyridine
      nucleotide NAADP is synthesized by an alternative route.

PMID- 11594754
TI  - Dissociation and subunit rearrangement of membrane-bound human C-reactive
      proteins.
AB  - As one of the most important acute-phase reactants in human serum, C-reactive
      protein plays its physiological roles mainly on membranes. Here we show that the
      human C-reactive protein is two-dimensionally crystallized upon specific
      adsorption on the phosphorylcholine ligand containing membranes by monolayer
      approach. The 2.0-nm resolution projection structure of the two-dimensional
      crystals analyzed by electron microscopy and image reconstruction reveals open
      ring-like pentamers in the crystals. The electron microscope graphs also show
      that the dissociated pentamers with open-ring-like structure occur in a closed
      packing region (not two-dimensionally crystallized). These results indicate a
      membrane-induced dissociation and rearrangement of hCRP, which may relate to the
      variety of hCRP's physiological functions.

PMID- 11594755
TI  - Adhesion via CD43 induces Syk activation and cell proliferation in TF-1 cells.
AB  - The effect of adhesion via CD43 (leukosialin, sialophorin) on cell proliferation
      and phosphorylation signaling were examined in a growth factor-dependent
      hematopoietic progenitor cell line, TF-1. TF-1 cells promptly resulted in death
      after withdrawal of growth factors. However, the viable cell number increased
      when TF-1 cells were cultured on anti-CD43 monoclonal antibody-coated plates. In
      this case, sustained activation of protein tyrosine kinase Syk and extracellular
      signal-regulated kinase (Erk) 1/2 were detected. Overexpression of exogenous Syk
      on TF-1 cells by the adenovirus vector system induced enhancement of the cell
      proliferation accompanied with enhancement of the Erk activation by a dominant
      positive effect. The signal transducer and activator of transcription (STAT) 5
      seemed not to be associated with the CD43-mediated cell proliferation. These
      results indicated that adhesion via CD43 induces the proliferation of TF-1 cells
      in the absence of growth factors in part by Syk-dependent Erk 1/2 signaling.

PMID- 11594756
TI  - Distinct phosphoinositide binding specificity of the GAP1 family proteins:
      characterization of the pleckstrin homology domains of MRASAL and KIAA0538.
AB  - GAP1, one of the Ras GTPase-activating protein families, includes four distinct
      genes (GAP1(m), GAP1(IP4BP), MRASAL (murine Ras GTPase-activating-like), and
      KIAA0538). It contains an amino-terminal tandem C2 domain, a GAP-related domain,
      and a carboxyl-terminal pleckstrin homology (PH) domain. Although the PH domains
      of GAP1(m) and GAP1(IP4BP) have been shown to be essential for membrane targeting
      via binding of specific phospholipids, little is known about the functions of the
      PH domains of MRASAL and KIAA0538. Herein, we show that the PH domain of MRASAL
      has binding activity toward PI(4,5)P(2) and PI(3,4,5)P(3), while the PH domain of
      KIAA0538 does not bind these phospholipids due to an amino acid substitution at
      position 592 (Leu-592). Mutation of the corresponding position of MRASAL (Arg-to
      Leu substitution at position 591) resulted in loss of the phospholipid binding
      activity. MRASAL proteins were localized at the plasma membrane in NIH3T3 cells,
      and this plasma membrane association was unchanged even after cytochalasin B or
      wortmannin treatment. By contrast, KIAA0538 and MRASAL (R591L) proteins were
      present in the cytosol. Our data indicate that the distinct phosphoinositide
      binding specificity of the PH domain is attributable to the distinct subcellular
      localization of the GAP1 family.

PMID- 11594757
TI  - Influence of the yihE gene of Shigella flexneri on global gene expression: on
      analysis using DNA arrays.
AB  - Inactivation of dsbA (disulfide bond formation), either by an insertion (Sh4,
      dsbA::kan) or by alteration of the active site (Sh42, dsbA33G), renders Shigella
      flexneri avirulent. However, Sh4 and Sh42 behave differently in many ways in
      vitro and in vivo. A gene of unknown function, yihE, up-stream and cotranscribed
      with dsbA, is thought to differentiate Sh4 and Sh42 as the kan insertion may
      result in a truncated unstable yihE-dsbA mRNA in Sh4. To gain insight into the
      function of yihE, DNA array hybridization was performed to study the genomic
      expression in Sh4, Sh42, and a newly constructed yihE mutant (Sh54). Compared to
      the wild-type, M90TS, Sh4, and Sh54 demonstrated significantly changed
      transcription levels of about 100 genes, of which many involved in energy
      metabolism and stress response were down- and up-regulated, respectively. In
      contrast, Sh42 showed altered transcription levels of only 20 genes. The results
      argue that yihE is principally responsible for the changed genomic expression in
      Sh4 and Sh54. Given the fact that the transcription of yihE-dsbA is regulated by
      the CpxRA two-component signal transduction system, yihE is probably involved in
      the extracytoplasmic stress response in a manor deserving further studies.

PMID- 11594758
TI  - Green tea constituent (--)-epigallocatechin-3-gallate inhibits topoisomerase I
      activity in human colon carcinoma cells.
AB  - DNA topoisomerases I and II are essential for cell survival and play critical
      roles in DNA metabolism and structure. Inhibitors of topoisomerase constitute a
      novel family of antitumor agents with demonstrated clinical activity in human
      malignancies. The clinical use of these agents is limited due to severe toxic
      effects on normal cells. Therefore, there is a need to develop novel, nontoxic
      topoisomerase inhibitors that have the ability to spare normal cells. Recent
      studies have shown that green tea and its major polyphenolic constituent,
      epigallocatechin-3-gallate (EGCG), impart growth inhibitory responses to cancer
      cells but not to normal cells. Based on the knowledge that EGCG induces DNA
      damage, cell cycle arrest, and apoptosis, we considered the possibility of the
      involvement of topoisomerase in the antiproliferative response of EGCG. Here, for
      the first time, we show that EGCG inhibits topoisomerase I, but not topoisomerase
      II in several human colon carcinoma cell lines. Based on this study it is
      tempting to suggest that combination of EGCG with other conventional
      topoisomerase inhibitors could be an improved strategy for treatment of colon
      cancer. The possible role of EGCG as a chemotherapeutic agent needs to be
      investigated.

PMID- 11594759
TI  - Stabilization of peroxisome proliferator-activated receptor alpha by the ligand.
AB  - Peroxisome proliferator-activated receptor (PPAR) constitutes a subfamily among a
      large group of ligand-activated transcription factors, the nuclear receptor
      superfamily. We studied the effects of ligand on the intracellular behaviors of
      PPARalpha. Although nuclear localization of PPARalpha was not affected by a
      selective ligand, Wy14643, we observed that exogenously expressed PPARalpha was
      rapidly degraded in HeLa cells, and the ligand significantly stabilized the
      protein. The stability of PPARalpha was also improved by coexpression of the
      heterodimer partner retinoid X receptor (RXR) alpha, and further stabilization
      was not observed with the ligand. These results indicate that PPARalpha is
      stabilized through heterodimerization with RXR, and the excess protein unpaired
      with RXR is rapidly turned over, if not bound by an appropriate ligand. These
      observations on PPARalpha are in sharp contrast to the ligand-stimulated
      degradation reported on PPARgamma. The ligand-dependent stabilization would have
      physiological significance when the synthesis of PPARalpha is elevated exceeding
      the available level of RXR.

PMID- 11594760
TI  - p53 unfolding detected by CD but not by tryptophan fluorescence.
AB  - Full-length human p53 protein was examined using tryptophan fluorescence and
      circular dichroism spectroscopy (CD) to monitor unfolding. No significant
      alteration in tryptophan fluorescence for the tetrameric protein was detectable
      over a wide range of either urea or guanidine hydrochloride concentrations, in
      contrast to results with the isolated DNA binding domain [Bullock et al. (1997)
      Proc. Natl. Acad. Sci. USA 94, 14338]. Under similar denaturant conditions, CD
      demonstrated significant protein unfolding for the full-length wild-type protein,
      with increased apparent structure loss compared to that detected during thermal
      denaturation [Nichols and Matthews (2001) Biochemistry 40, 3847]. Examination of
      X-ray structures containing two of the four tryptophan residues of a p53 monomer
      suggested local environments consistent with quenched fluorophores. Exploration
      of p53 fluorescence using potassium iodide as a quencher confirmed that these
      fluorophores are already substantially quenched in the native structure, and this
      quenching is not relieved during protein unfolding.

PMID- 11594761
TI  - Lipoxygenase may be involved in cationic liposome-induced macrophage apoptosis.
AB  - The purpose of this study was to determine the source of reactive oxygen species
      (ROS) generation and the contribution of ROS to the apoptosis of RAW264.7 cells
      induced by cationic liposomes. Cationic liposome-induced apoptosis was inhibited
      by lipoxygenase inhibitors, but not inhibitors of NADPH-oxidase, xanthine oxidase
      or cyclooxygenase. ROS generation induced by cationic liposomes was also
      inhibited by the lipoxygenase inhibitor NDGA. Furthermore, lipid peroxidation was
      observed following liposome treatment, but the apoptosis was not inhibited by the
      antioxidant alpha-tocopherol. These findings suggested that lipoxygenase is
      responsible for ROS generation, and ROS but not lipid peroxidation acts as a key
      mediator in the progress of apoptosis induced by cationic liposomes.

PMID- 11594762
TI  - Characterization of thermal stability of the Escherichia coli Fapy-DNA
      glycosylase.
AB  - Thermal stability of Escherichia coli Fpg protein was studied using far-UV
      circular dichroism and intrinsic fluorescence. Experimental data indicate that
      Fpg irreversibly aggregates under heating above 35 degrees C. Heat aggregation is
      preceded by tertiary conformational changes of Fpg. However, the secondary
      structure of the fraction that does not aggregate remains unchanged up to
      approximately 60 degrees C. The kinetics of heat aggregation occurs with an
      activation enthalpy of approximately 21 kcal/mol. The fraction of monomers
      forming aggregates decreases with increasing urea concentration, with essentially
      no aggregation observed above approximately 3 M urea, suggesting that heat
      aggregation results from hydrophobic association of partially unfolded proteins.
      With increasing urea concentration, Fpg unfolds in a two-state reversible
      transition, with a stability of approximately 3.6 kcal/mol at 25 degrees C. An
      excellent correlation is observed between the unfolded fraction and loss of
      activity of Fpg. A simple kinetic scheme that describes both the rates and the
      extent of aggregation at each temperature is presented.

PMID- 11594763
TI  - Human endomucin is an endothelial marker.
AB  - The identification of novel endothelial markers is important in the study of
      angiogenesis, and may have potential uses in cancer diagnosis and treatment. We
      have isolated potential markers of tumor angiogenesis by screening human
      umbilical vein endothelial cells (HUVECs) treated with tumor conditioned media.
      Using suppression subtractive hybridization (SSH), we found endomucin, a
      potential cell surface marker upregulated in this system. Human endomucin is
      predicted to encode a 261-aa, 27.5-kDa protein with a transmembrane sequence and
      multiple glycosylation sites. Northern and in situ hybridization studies show
      that human endomucin expression is largely, if not uniquely, endothelial cell
      specific. Human endomucin is present abundantly in highly vascular tissues such
      as heart, kidney, and lung. It is seen in human aortic endothelial cells (HAECs)
      as well as in human microvascular endothelial cells (HMVECs). Furthermore, its
      expression is increased when endothelial cells are proliferating or are
      stimulated by tumor-conditioned media or specific angiogenic factors such as bFGF
      (basic fibroblast growth factor) and TNFalpha (tumor necrosis factor), suggesting
      that endomucin may have a role in tumor angiogenesis.

PMID- 11594764
TI  - Identification of Nash1, a novel protein containing a nuclear localization
      signal, a sterile alpha motif, and an SH3 domain preferentially expressed in mast
      cells.
AB  - By using a serial analysis of gene expression (SAGE), we have identified a novel
      full-length cDNA that is preferentially expressed in human cord blood-derived
      mast cells. The predicted protein showed unique primary structure with a nuclear
      localization signal (NLS), a sterile alpha motif (SAM), and a Src homology 3
      domain (SH3) (termed Nash1). Nash1 was mapped to human chromosome 21q11.1 and
      highly expressed in spleen, liver, peripheral blood, and mast cell lines. In
      consistent with the presence of NLS, Nash1 was localized in the nucleus.
      Interestingly, screening gene databases for Nash1-related sequences revealed the
      existence of a Nash1-related gene termed SLY that was preferentially detected in
      lymphoid cells. We also found at least two additional candidates for this gene
      family in the database. These findings suggested that Nash1 and Nash1-related
      proteins consisted of a novel family of signaling/adaptor proteins, and Nash1
      might function as a signaling component of mast cells, possibly in the nucleus.

PMID- 11594765
TI  - Tartrate-resistant acid phosphatase facilitates hydroxyl radical formation and
      colocalizes with phagocytosed Staphylococcus aureus in alveolar macrophages.
AB  - Tartrate-resistant acid phosphatase (TRAP) is an enzyme expressed specifically in
      osteoclasts and activated macrophages, two phagocytosing cell types originating
      from the same hematopoietic stem cells. TRAP contains a binuclear iron centre
      which has been shown to generate reactive oxygen species (ROS). In this study
      murine macrophage like cell line RAW-264 overexpressing TRAP was shown to produce
      elevated levels of hydroxyl radicals compared to parental cells. TRAP transfected
      cells also had reduced growth rate indicating harmful effects of excessive
      intracellular ROS levels. Using TRAP specific antibody TRAP protein was shown in
      alveolar macrophages partially colocalize with late endosomal/lysosomal markers
      Rab7, Lamp 1 and MHC II molecules that bind antigenic peptides. TRAP also
      colocalized into compartments where Staphylococcus aureus were phagocytosed.
      These results suggest that TRAP may have an important biological function in the
      defence mechanism of macrophages by generating intracellular ROS which would be
      targeted to destroy phagocytosed foreign material.

PMID- 11594766
TI  - Lithium suppresses signaling and induces rapid sequestration of beta2-adrenergic
      receptors.
AB  - Lithium is a monovalent cation used therapeutically to treat a range of affective
      disorders (1), although the cellular mechanisms of lithium regulation that might
      contribute to its therapeutic effects at the level of neurotransmitter receptors
      are not known. Herein we report the ability of lithium to stimulate the
      internalization of beta2-adrenergic receptors. Lithium treatment of A431 human
      epidermoid carcinoma cells resulted in a rapid, prominent desensitization and
      internalization of beta2-adrenergic receptors. The ability of these receptors to
      generate a cyclic AMP response was strongly inhibited by lithium, at
      concentrations therapeutic in humans. Receptors for the serotonin (5HT1c) and for
      opiates (mu-opioid), in sharp contrast, resisted the effects of lithium on
      internalization. These data provide the first receptor-based mechanism to be
      described for lithium that could explain, in part, the therapeutic effects of
      lithium on affective disorders.

PMID- 11594767
TI  - Isolation, characterization, and transplantation of bone marrow-derived
      hepatocyte stem cells.
AB  - Recently it was shown that a population of cells in the bone marrow-expressing
      hematopoietic stem cell antigens could differentiate into hepatocytes. However,
      explicitly committed hepatocyte progenitors, which exhibit highly differentiated
      liver functions, immediately upon isolation, have not yet been isolated from bone
      marrow. After studying common antigens on blast-like cells in fetal and adult
      regenerating cholestatic rat livers and human regenerating and malignant livers,
      we hypothesized that beta-2-microglobulin-negative (beta(2)m(-)) cells might
      represent dedifferentiated hepatocytes and/or their progenitors. Utilizing a two
      step magnetic bead cell-sorting procedure, we show that in bone marrow from rat
      and human, beta(2)m(-)/Thy-1(+) cells consistently express liver-specific genes
      and functions. After intraportal infusion into rat livers, bone marrow-derived
      hepatocyte stem cells (BDHSC) integrated with hepatic cell plates and
      differentiated into mature hepatocytes. In a culture system simulating liver
      regeneration and containing cholestatic serum, these cells differentiated into
      mature hepatocytes and metabolized ammonia into urea. This differentiation was
      dependent on a yet nondescript humoral signal existing in the cholestatic serum.
      Transmission electron microscopy and three-dimensional digital reconstruction
      confirmed hepatocyte ultrastructure of cultured BDHSC.

PMID- 11594768
TI  - Developmental expression and localization of IA-2 mRNA in mouse neuroendocrine
      tissues.
AB  - Islet antigen (IA)-2 is a novel autoantigen of insulin-dependent diabetes
      mellitus (IDDM), and belongs to a new class within the receptor-type protein
      tyrosine phosphatase (PTP) family characterized by lack of PTP enzymatic activity
      with conventional substrates. Its expression is restricted primarily to the
      pancreas, pituitary, and brain with the highest level in the brain. IA-2 mRNA
      expressions in the brain, pituitary and pancreas of 1-, 4-, and 8-week-old mice
      were examined. In situ hybridization of the brain revealed that IA-2 mRNA was
      expressed in the cerebral cortex, hippocampus, thalamus, choroid plexus,
      hypothalamus, Purkinje cells, and granular layer of the cerebellum. In the
      pituitary, IA-2 mRNA was located in the anterior and posterior pituitary by in
      situ hybridization. The pattern of IA-2 mRNA expression in normal male mouse
      brain at 1, 4, and 8 weeks of age by the Northern blot analysis was similar to
      that in the pituitary by RT-PCR analysis. The expression level was higher at 4
      weeks and lower at 1 week of age. In the pancreas, IA-2 mRNA expressions detected
      by RT-PCR were highest at 8 weeks of age. These results indicated that the amount
      of mRNA expression increased in accordance to development in brain, pituitary,
      and pancreas.

PMID- 11594769
TI  - Interaction of the CopZ copper chaperone with the CopA copper ATPase of
      Enterococcus hirae assessed by surface plasmon resonance.
AB  - Intracellular copper routing in Enterococcus hirae can be accomplished by the
      CopZ metallochaperone. Using surface plasmon resonance analysis, we show here
      that CopZ interacts with the CopA copper ATPase. The binding affinity of CopZ for
      CopA was increased in the presence of copper, due to a 15-fold lower dissociation
      rate constant. Mutating the N-terminal copper binding motif of CopA from CxxC to
      SxxS abolished this copper-induced effect. Moreover, CopZ failed to show an
      interaction with an unrelated copper binding protein used as a control. These
      results show that (i) the CopA copper ATPase specifically interacts with the CopZ
      chaperone, (ii) this interaction is based on protein-protein interaction, and
      (iii) surface plasmon resonance is a novel tool for quantitative analysis of
      metallochaperone-target interactions.

PMID- 11594770
TI  - Molecular cloning and characterization of mouse Tspan-3, a novel member of the
      tetraspanin superfamily, expressed on resting dendritic cells.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells and play an
      essential role for triggering T-cell-mediated immune responses. In search for
      novel cell surface molecules expressed on DCs involved in T cell priming by
      representational differential analysis, we identified a mouse homologue of Tspan
      3 (mTspan-3), a novel member of the tetraspanin superfamily. The mTspan-3
      consists of four hydrophobic, putative transmembrane regions, forming a small and
      a large extracellular loop, with short intracellular amino and carboxil tails.
      Although the mTspan-3 is expressed on a variety of immune cell types including
      resting DCs, its expression on DCs is downregulated during activation induced by
      cross-linking CD40 with anti-CD40 monoclonal antibody. These results suggest that
      mTspan-3 may be involved in the function of DCs in association with T cell
      stimulation.

PMID- 11594771
TI  - Conformational change in the herpes simplex single-strand binding protein induced
      by DNA.
AB  - Protease digestion of the herpes simplex virus type 1 major single-strand DNA
      binding protein ICP8 showed that the cleavage patterns observed in the presence
      and absence of single-stranded DNA oligonucleotides are substantially different
      with protection of cleavage sites between amino acids 293 and 806 observed in the
      presence of oligonucleotide. Experiments using ICP8 modified with fluorescein-5
      maleimide (FM) showed that the fluorescence signal exhibited increased
      susceptibility to antibody quenching and a significant decrease in polarization
      of the FM fluorescence was observed in the presence compared to the absence of
      oligonucleotide. Taken together, these results indicate that ICP8 undergoes a
      conformational change upon binding to single-stranded DNA.

PMID- 11594772
TI  - Regulation of UCP1, UCP2, and UCP3 mRNA expression in brown adipose tissue, white
      adipose tissue, and skeletal muscle in rats by estrogen.
AB  - The effects of ovariectomy (OVX) and estrogen substitution on body weight, body
      composition, food intake, weight gain, and expression of uncoupling proteins
      (UCPs) in brown adipose tissue (BAT), white adipose tissue (WAT), and skeletal
      muscle were studied in four groups of rats: (1) Sham-operated rats (N = 8), (2)
      ovariectomized rats (OVX - E) (N = 8), (3) estrogen-treated OVX rats (OVX + E) (N
      = 8), and (4) OVX rats on energy restriction (OVX - E + D) (N = 8). OVX was
      associated with an increase in food intake and body weight gain during a 5-week
      study period compared to sham-operated rats. The estrogen-substituted rats had a
      significantly lower food intake and weight gain during the 5 weeks compared to
      the sham-operated group. However, we also included a nontreated OVX group that
      was allowed to eat only enough chow to match the weight gain of the sham-operated
      group. To match the weight gain in the two groups, the OVX group had to consume
      16% less chow than the sham-operated group. In BAT, the UCP1 expression was
      significantly lower in estrogen-deficient rats compared to either intact rats or
      estrogen-substituted rats, whereas UCP2 and UCP3 mRNA expression was similar in
      BAT from all four groups. In WAT, both estrogen-deficient groups had
      significantly lower UCP2 mRNA expression compared to the control rats and
      estrogen-treated rats; In contrast, the UCP3 mRNA expression in WAT was similar
      in all four groups. Finally, in skeletal muscle the OVX group on mild energy
      restriction had reduced UCP3 mRNA expression compared to control, OVX, and
      estrogen-treated rats. In contrast, the UCP2 mRNA expression in skeletal muscle
      was similar in all four groups. Thus, the findings that estrogen deficiency is
      followed by reduced UCP1 expression in BAT and reduced UCP2 expression in WAT in
      association with weight gain probably caused by a decrease in energy expenditure
      might indicate that UCPs play a role for the estrogen-mediated changes in body
      weight and energy expenditure.

PMID- 11594773
TI  - Requirement of c-jun N-terminal kinase for apoptotic cell death induced by
      farnesyltransferase inhibitor, farnesylamine, in human pancreatic cancer cells.
AB  - Farnesyltransferase inhibitors (FTIs) represent a novel class of anticancer drugs
      and are now in clinical trial. We have previously shown that farnesylamine,
      synthetic isoprenoid-linked with "amine" which acts as a potent FTI, induces
      apoptosis in human pancreatic cancer cells through the ras signaling cascade.
      Since the effect of FTI is usually "cytostatic" rather than "cytotoxic", we
      speculated another apoptotic machinery of farnesylamine in addition to the effect
      of FTI. Farnesylamine induced sustained activation of c-jun N-terminal kinase
      (JNK), which was not caused by other FTI, FTI-277. Blockage of JNK activity by
      dominant-negative mutant abrogated the DNA laddering and significantly reduced
      "cytotoxic" effect of farnesylamine. Strikingly similar effect on JNK activation
      and apoptosis was induced by structurally related long-chain fatty amine (LFA),
      oleylamine, but not by farnesol, an isoprenoid analogue of farnesylamine without
      "amine." Taken together, apoptosis induction through JNK activation by
      farnesylamine based on the LFA structure rather than an effect of FTI.

PMID- 11594774
TI  - Insulin, insulin-like growth factor-I, and platelet-derived growth factor
      activate extracellular signal-regulated kinase by distinct pathways in muscle
      cells.
AB  - We have investigated the signaling pathways initiated by insulin, insulin-like
      growth factor-1 (IGF-I), and platelet-derived growth factor (PDGF) leading to
      activation of the extracellular signal-regulated kinase (ERK) in L6 myotubes.
      Insulin but not IGF-I or PDGF-induced ERK activation was abrogated by Ras
      inhibition, either by treatment with the farnesyl transferase inhibitor FTP III,
      or by actin disassembly by cytochalasin D, previously shown to inhibit Ras
      activation. The protein kinase C (PKC) inhibitor bisindolylmaleimide abolished
      PDGF but not IGF-I or insulin-induced ERK activation. ERK activation by insulin,
      IGF-I, or PDGF was unaffected by the phosphatidylinositol 3-kinase inhibitor
      wortmannin but was abolished by the MEK inhibitor PD98059. In contrast,
      activation of the pathway involving phosphatidylinositol 3-kinase (PI3k), protein
      kinase B, and glycogen synthase kinase 3 (GSK3) was mediated similarly by all
      three receptors, through a PI 3-kinase-dependent but Ras- and actin-independent
      pathway. We conclude that ERK activation is mediated by distinct pathways
      including: (i) a cytoskeleton- and Ras-dependent, PKC-independent, pathway
      utilized by insulin, (ii) a PKC-dependent, cytoskeleton- and Ras-independent
      pathway used by PDGF, and (iii) a cytoskeleton-, Ras-, and PKC-independent
      pathway utilized by IGF-I.

PMID- 11594775
TI  - Matrix metalloproteinase-2 and -9 in bile as a marker of liver metastasis in
      colorectal cancer.
AB  - Matrix metallproteinases (MMP)-2 and -9 are associated with cancer invasion and
      metastasis. MMP-2 and MMP-9 activities have never been assayed in bile. In the
      present study we investigated whether MMP-2 and -9 activities in the bile could
      be a marker for evaluation of liver metastasis in colorectal cancer. Fifty-three
      patients underwent colorectal resection for histologically verified
      adenocarcinoma. Twenty-six patients had colorectal cancer without liver
      metastasis and 27 patients had metastatic liver tumor. Six patients were studied
      as carcinoma-free control. MMP-2 and MMP-9 activities were assayed in bile using
      gelatin zymography and quantitated. Active MMP-2 activity of colorectal cancer
      with liver metastasis group (24.1 +/- 2.5 pixel count) was significantly higher
      than that of colorectal cancer without liver metastasis group (11.4 +/- 1.3 pixel
      count) (P < 0.001) or of control group (6.4 +/- 1.0 pixel count) (P < 0.001).
      Active MMP-9 was not detected in bile. ProMMP-9 activity of colorectal cancer
      with liver metastasis group (530.3 +/- 127.5 pixel count) was significantly
      higher than that of colorectal cancer without liver metastasis group (213.9 +/-
      33.2 pixel count) (P = 0.008). This is the first report showing that the levels
      of active MMP-2 and proMMP-9 in bile were significantly higher in liver
      metastasis of colorectal cancer than in metastasis-free colorectal cancer. The
      results suggest that activities of active MMP-2 and proMMP-9 in the bile may be
      useful markers for predicting liver metastasis in colorectal cancer.

PMID- 11594776
TI  - Immunological study on circulating murine osteoprotegerin/osteoclastogenesis
      inhibitory factor (OPG/OCIF): possible role of OPG/OCIF in the prevention of
      osteoporosis in pregnancy.
AB  - Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a soluble
      member of the tumor necrosis factor receptor family and plays a crucial role in
      the negative regulation of osteoclastic bone resorption. We have immunized
      OPG/OCIF knockout mice with murine rOPG/rOCIF and established a panel of
      hybridomas producing monoclonal antibodies (mAbs) to murine rOPG/rOCIF. Utilizing
      the mAbs, we developed enzyme-linked immunosorbent assay (ELISA) systems: one
      detecting both homodimeric and monomeric forms of murine OPG/OCIF and the other
      detecting only dimeric form of murine OPG/OCIF. With the aid of these ELISA
      systems we showed that OPG/OCIF is present mainly as a monomer in murine blood.
      The concentration of OPG/OCIF in normal mouse sera was approximately 500 pg/ml
      and there was no statistical difference in the serum concentration of OPG/OCIF
      among genders, age, and strains. Interestingly, the concentration of circulating
      OPG/OCIF in mouse markedly increased during pregnancy. The result indicated that
      circulating OPG/OCIF plays an important role in the protection of bone from
      excess resorption during pregnancy in mammals.

PMID- 11594777
TI  - Astaxanthin and peridinin inhibit oxidative damage in Fe(2+)-loaded liposomes:
      scavenging oxyradicals or changing membrane permeability?
AB  - Astaxanthin and peridinin, two typical carotenoids of marine microalgae, and
      lycopene were incorporated in phosphatidylcholine multilamellar liposomes and
      tested as inhibitors of lipid oxidation. Contrarily to peridinin results,
      astaxanthin strongly reduced lipid damage when the lipoperoxidation promoters
      H(2)O(2), tert-butyl hydroperoxide (t-ButOOH) or ascorbate-and Fe(2+):EDTA were
      added simultaneously to the liposomes. In order to check if the antioxidant
      activity of carotenoids was also related to their effect on membrane
      permeability, the peroxidation processes were initiated by adding the promoters
      to Fe(2+)-loaded liposomes (encapsulated in the inner aqueous solution). Despite
      that the rigidifying effect of carotenoids in membranes was not directly measured
      here, peridinin probably has decreased membrane permeability to initiators (t
      ButOOH > ascorbate > H(2)O(2)) since its incorporation limited oxidative damage
      on iron-liposomes. On the other hand, the antioxidant activity of astaxanthin in
      iron-containing vesicles might be derived from its known rigidifying effect and
      the inherent scavenging ability.

PMID- 11594778
TI  - Phosphorylation of human N-myristoyltransferase by N-myristoylated SRC family
      tyrosine kinase members.
AB  - N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the
      cotranslational and/or posttranslational transfer of myristate to the amino
      terminal glycine residue of a number of important proteins especially the non
      receptor tyrosine kinases whose activity is important for tumorigenesis. Human
      NMT was found to be phosphorylated by non-receptor tyrosine kinase family members
      of Lyn, Fyn and Lck and dephosphorylated by the Ca(2+)/calmodulin-dependent
      protein phosphatase, calcineurin. Deletion of 149 amino acids from the N-terminal
      end resulted in the absence of phosphorylation suggesting that the
      phosphorylation sites are located in the N-terminal end of NMT. Furthermore, a
      site-directed mutagenesis study indicated that substitution of tyrosine 100 with
      phenylalanine served NMT as a poor substrate for the Lyn kinase. A synthetic
      peptide corresponding to the amino-terminal region encompassing tyrosine 100 of
      NMT served as a good substrate for the Lyn and Fyn kinases. Our studies also
      indicated that NMT was found to interact with Lyn through its N-terminal end in a
      phosphorylation-dependent manner. This is the first study demonstrating the cross
      talk between NMT and their myristoylated protein substrates in signaling
      pathways.

PMID- 11594779
TI  - Ectopic expression of the coxsackievirus and adenovirus receptor increases
      susceptibility to adenoviral infection in the human cervical cancer cell line,
      SiHa.
AB  - The expression level of the coxsackievirus and adenovirus receptor (CAR) gene in
      human cervical cancer cell lines (Hela, Caski, HT-3, and SiHa) appears to be
      correlated with their susceptibility to adenoviral vector-based gene transfer.
      Hela, Caski, and HT-3 cells, which express the CAR molecule on the cell surface,
      showed a higher susceptibility to infection of AdCMVGFP than SiHa cells with no
      detectable level of CAR expression. Transient expression of the CAR gene in SiHa
      cells dramatically enhanced the susceptibility to adenoviral infection.
      Furthermore, SiHa-CAR, a stable transfectant which expresses the CAR gene showed
      a highly increased susceptibility to adenoviral infection in contrast to SiHa.
      These results demonstrate that the low susceptibility of SiHa to adenoviral
      infection is closely related to its loss of the CAR gene expression. In addition,
      the low infection efficacy can be overcome by the ectopic expression of the CAR
      gene. These results also give insight into a possible application of the CAR gene
      to adenovirus-mediated gene delivery.

PMID- 11594780
TI  - Iron supplementation and oxidative damage to DNA in healthy individuals with high
      plasma ascorbate.
AB  - Previously, we have investigated the potential for a pro-oxidant interaction of
      iron and ascorbate in vivo in iron and ascorbate cosupplementation or ascorbate
      supplementation studies. In this study, for the first time, the effects of iron
      supplementation on oxidative damage to DNA in healthy individuals with plasma
      ascorbate levels at the upper end of the normal range were examined. Forty female
      and male volunteers (mean plasma ascorbate approximately equal to 70 micromol/L)
      were supplemented with a daily dose of syrup (ferrous glycine sulphate equivalent
      to 12.5 mg iron) for 6 weeks. Serum ferritin, transferrin bound iron, %
      saturation of transferrin and plasma ascorbate were assessed and the mean dietary
      intakes of all subjects were estimated through food frequency questionnaires.
      Oxidative damage to DNA bases from white blood cells was measured by gas
      chromatography/mass spectrometry with selected-ion monitoring (GC/MS-SIM), using
      isotope-labelled standards for quantification. Iron supplementation did not
      affect any of the iron status parameters. There were also no detrimental effects,
      over the period under investigation, in terms of oxidative damage to DNA.
      However, the effects of larger doses or of longer supplementation periods should
      also be investigated.

PMID- 11594781
TI  - Involvement of tyrosine phosphatase PTP1D in the inhibition of interleukin-6
      induced Stat3 signaling by alpha-thrombin.
AB  - We previously demonstrated that exposure of CCL39 lung fibroblasts to alpha
      thrombin inhibits interleukin-6 (IL-6)-induced tyrosine phosphorylation of Stat3
      (signal transducers and activators of transcription 3) via activation of mitogen
      activated protein (MAP) kinase kinase 1 [Bhat et al. (1998) Arch. Biochem.
      Biophys. 350, 307-314]. In this study, using CCL39/MRC-5 cells, we investigated
      if additional signaling intermediates are involved in alpha-thrombin's inhibitory
      effects on IL-6-induced Stat3 signaling. We also determined if alpha-thrombin
      inhibits oncostatin M (OSM)-induced Stat3/Stat1, and interferon-gamma (IFN-gamma)
      induced Stat1 tyrosine phosphorylation. We demonstrate that, although both IL-6
      and OSM belong to the same cytokine family, alpha-thrombin inhibited only the IL
      6-induced Stat3 tyrosine phosphorylation. The tyrosine phosphatase PTP1D
      coprecipitated with Stat3 from alpha-thrombin + IL-6, but not from alpha-thrombin
      + OSM-treated cells. Pretreatment of cells with a phosphatase inhibitor reversed
      the inhibitory actions of alpha-thrombin, suggesting a role for PTP1D in alpha
      thrombin-mediated inhibition of IL-6-induced Stat3 signaling. Interestingly,
      alpha-thrombin failed to inhibit OSM- and IFN-gamma-induced Stat1 tyrosine
      phosphorylation. Cytokine-specific inhibition of the Stat3 signaling involving
      MAP kinase kinase 1 and PTP1D by alpha-thrombin may play an important role in
      regulation of gene expression.

PMID- 11594782
TI  - Single-molecule imaging by atomic force microscopy of the native chaperonin
      complex of the thermophilic archaeon Sulfolobus solfataricus.
AB  - The chaperonin of the extremely thermophilic archaeon Sulfolobus solfataricus has
      been imaged for the first time under native conditions using the atomic force
      microscope. This technique allows to visualize the structure of biomolecules in
      solution under physiological conditions providing a nanometer resolution
      topographic image of the sample. Single molecule studies can reveal fine
      structural details, providing a powerful insight into the active conformation of
      a macromolecule, and also allowing to detect different conformational states
      corresponding to functional changes.

PMID- 11594783
TI  - Mutational effects on thermostable superoxide dismutase from Aquifex pyrophilus:
      understanding the molecular basis of protein thermostability.
AB  - We designed two mutants of superoxide dismutase (SOD), one is thermostable and
      the other is thermolabile, which provide valuable insight to identify amino acid
      residues essential for the thermostability of the SOD from Aquifex pyrophilus
      (ApSOD). The mutant K12A, in which Lys12 was replaced by Ala, had increased
      thermostability compared to that of the wild type. The T(1/2) value of K12A was
      210 min and that of the wild type was 175 min at 95 degrees C. However, the
      thermostability of the mutant E41A, which has a T(1/2) value of 25 min at 95
      degrees C, was significantly decreased compared to the wild type of ApSOD. To
      explain the enhanced thermostability of K12A and thermolabile E41A on the
      structural basis, the crystal structures of the two SOD mutants have been
      determined. The results have clearly shown the general significance of hydrogen
      bonds and ion-pair network in the thermostability of proteins.

PMID- 11594784
TI  - Differential chemosensitizing effect of two glucosylceramide synthase inhibitors
      in hepatoma cells.
AB  - It has been proposed that ceramide mediates anthracyclin-induced apoptosis and
      that drug resistance may arise due to upregulated removal of this active lipid
      through glucosylation. We report that HepG2 hepatoma cells displayed only a
      modest apoptotic response to doxorubicin treatment, accompanied by a substantial
      elevation of ceramide levels only at toxic drug concentrations. D,L-threo-1
      phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and D,L-threo-1-phenyl-2
      hexadecanoylamino-3-pyrrolidino-1-propanol (PPPP), used at concentrations causing
      a 90% inhibition of ceramide glucosylation, enhanced doxorubicin-elicited
      ceramide elevation, but only PDMP potentiated apoptosis. Exogenously administered
      ceramide had only a marginal apoptotic effect on HepG2 cells; moreover, even in
      this case, apoptosis was propagated by PDMP but not by PPPP. PDMP moderately
      inhibited P-glycoprotein activity only at the highest concentration tested, but
      its chemosensitizing effect was still outstanding at lower concentrations, at
      which P-gp inhibition was no longer observed. These results demonstrate that the
      chemosensitizing effect of PDMP is, at least partly, independent from its
      activity as a glucosylceramide synthase inhibitor. Moreover, P-glycoprotein
      inhibition is not central to the phenomenon.

PMID- 11594785
TI  - Association between oxidative stress and bone mineral density.
AB  - Free radicals have been shown to be involved in bone resorption in vitro and in
      rodents. We studied the effect of oxidative stress on bone mineral density (BMD)
      in 48 women and 53 men from a population-based study. The levels of 8-iso
      PGF(2alpha) (a major F(2)-isoprostane and a biomarker of oxidative stress) and a
      control, 15-keto-dihydro-PGF(2alpha) (a biomarker of inflammatory response), were
      measured in urinary samples and their association with BMD and quantitative
      ultrasound (QUS) measurements were examined. In multivariate linear regression
      analyses, 8-iso-PGF(2alpha) levels were negatively associated with both BMD and
      QUS. In contrast, no association was found for 15-keto-dihydro-PGF(2alpha). Our
      findings establish a biochemical link between increased oxidative stress and
      reduced bone density and provide a rational for further studies investigating the
      role of pro- and antioxidants in osteoporosis.

PMID- 11594786
TI  - Biochemical characterization and tissue distribution of human SULT2B1.
AB  - The human hydroxysteroid sulfotransferase (SULT) family is comprised of two
      subfamilies, SULT2A1 and SULT2B1. We characterized the substrate specificity, in
      vitro biochemical properties, and tissue distribution patterns of human SULT2B1a
      and SULT2B1b. In contrast to the wide substrate specificity of SULT2A1, SULT2B1a
      and SULT2B1b specifically catalyzed the sulfonation of 3beta-hydroxysteroids with
      high catalytic efficiency. Both SULT2B1 enzymes also sulfonated
      dihydrotestosterone. In vitro studies revealed that the biochemical properties of
      SULT2B1a and SULT2B1b were not significantly different from each other. However,
      tissue expression analysis suggested that they are differentially regulated. In
      contrast to the limited tissue distribution of SULT2A1, SULT2B1 was detected in a
      variety of hormone-responsive tissues including placenta, ovary, uterus, and
      prostate. The catalytic activity toward dehydroepiandrosterone and
      dihydrotestosterone, biologically important androgens, coupled with expression in
      prostate suggests that SULT2B1 may play a novel regulatory role that protects
      against the mitogenic effects of androgens.

PMID- 11594787
TI  - The rat interleukin 10 receptor: cloning and sequencing of cDNA coding for the
      alpha-chain protein sequence, and demonstration by western blotting of expression
      in the rat brain.
AB  - cDNA coding for the alpha chain of the rat interleukin 10 (IL-10) receptor was
      amplified by polymerase chain reaction (PCR), cloned and sequenced. The nucleic
      acid coding sequence exhibited 88% and 68% homology with the mouse and human IL
      10 receptor sequences, respectively. The translated protein exhibited 83% and 61%
      homology with the mouse and human IL-10 receptor proteins. Specific antibodies
      were raised to the extracellular domain of the rat IL-10 receptor expressed as a
      secreted protein in recombinant Drosophila S2 cells. Western blotting using these
      antibodies demonstrated the presence of the IL-10 receptor in five major regions
      of the rat brain (cortex, cerebellum, hippocampus, hypothalamus and pituitary),
      supporting a role for IL-10 as a central regulator of inflammation.

PMID- 11594788
TI  - Disparate effects of interleukin 11 and thrombopoietin on megakaryocytopoiesis in
      vitro.
AB  - The effects of interleukin-11 (IL-11) and thrombopoietin (TPO) on murine
      megakaryocytopoiesis were studied using a serum-free culture system. Acting
      alone, both IL-11 and TPO increased the number of acetylcholinesterase
      (AchE)(+)cells (megakaryocytes), the latter being more potent than the former.
      TPO, but not IL-11, increased the mean AchE activity per megakaryocyte (AchE
      activity/megakaryocyte). TPO increased both the number of megakaryocytes with
      high ploidy, and of those with low ploidy. In contrast, IL-11 increased only the
      number of megakaryocytes with high ploidy. The effect of TPO on megakaryocyte
      ploidy was stronger than that of IL-11. Both IL-11 and TPO increased the
      proportion of large megakaryocytes, but the latter was more potent than the
      former. While the stimulatory effects of IL-11 and TPO on the number of
      megakaryocytes were enhanced by IL-3 or stem cell factor (SCF), synergism of IL
      11 or TPO with IL-3 or SCF in stimulating AchE activity/megakaryocyte was
      inconsistent. IL-11 and TPO stimulated the formation of colony-forming units of
      megakaryocyte in the presence of IL-3, but not alone, with similar maximum colony
      numbers for both cytokines. Our findings thus demonstrate that IL-11 principally
      stimulates megakaryocyte maturation rather than the proliferation of
      megakaryocytes, whereas TPO stimulates both.

PMID- 11594789
TI  - Characterization and humanization of a monoclonal antibody that neutralizes human
      leukocyte interferon: a candidate therapeutic for IDDM and SLE.
AB  - We have developed a panel of murine monoclonal antibodies that recognize human
      interferon alpha. One of these mononclonal antibodies binds and neutralizes, with
      high affinity, all of seven tested recombinant human interferon alphas. This
      mononclonal antibody also neutralizes the interferon activity present in two
      independent pools of interferon alphas prepared following stimulation of human
      peripheral blood leukocytes. The complementary determining regions from this
      murine mononclonal antibody were transferred to a human IgG2 heavy chain and to a
      human kappa1 light chain. In addition, six (heavy chain) and two (light chain)
      amino acids were transferred from the framework regions. This generated a
      humanized mononclonal antibody that retained the specificity of the mouse parent.
      The humanized anti-interferon alpha antibody is a candidate therapeutic for those
      diseases, such as insulin-dependent diabetes, systemic lupus erythematosis,
      psoriasis and Crohn's disease, which are all characterized by pathological
      expression of interferon alpha.

PMID- 11594790
TI  - Interleukin 1beta as stimulator of the rat thymus.
AB  - The effects of interleukin 1beta administration on the thymus of adult and old
      rats were studied in order to study the interactions between the nervous and
      immune systems and to confirm the important role played by catecholaminergic
      nerve fibres (CNF) in the regulation of thymic functions. Moreover, chemical
      sympathectomy was performed in a group of rats to study the effects on thymus of
      the destruction of the majority of CNF. Our results indicate that thymic
      stimulation (performed by means of interleukin 1beta) induces substantial changes
      in the fresh weight of the whole thymus, as well as in the thymic
      microenvironment, thymic nerve fibres, CNF, neuropeptide Y (NPY)-like positive
      nerve fibres and total amount of both proteins and norepinephrine in rat thymic
      tissue homogenates. The majority of CNF are destroyed after chemical
      sympathectomy with 6-OH-Dopamine (DA) and remain unchanged after treatment with
      interleukin 1beta.

PMID- 11594791
TI  - Elevated serum levels of TNF-alpha, sTNF-RI and sTNF-RII in murine
      schistosomiasis correlate with schistosome oviposition and circumoval granuloma
      formation.
AB  - Levels of circulating tumour necrosis factor (TNF-alpha) and its soluble
      receptors are elevated in chronic human schistosomiasis. However, the kinetics of
      TNF-alpha production and release of its soluble receptors have not been studied
      in humans or animals. Here we report on increased levels of TNF-alpha and its
      soluble receptors in murine schistosomiasis, beginning with schistosome
      oviposition and circumoval granuloma formation. TNF-alpha, sTNF-RI and sTNF-RII
      were measured in sera of mice infected with Schistosoma mansoni each week for 10
      weeks postinfection. TNF-alpha levels increased gradually in all mice during the
      first 3 weeks. From 6th week postinfection, TNF-alpha levels in infected mice
      increased steadily, whereas those of uninfected mice remained essentially
      unchanged. sTNF-RI levels fluctuated in all mice during the first 3 weeks, and
      increased in infected mice during the following 5 weeks. sTNF-RII levels were
      similar in all mice for the first 4 weeks but increased in infected mice
      throughout the remainder of the experimental period. These data may be helpful in
      understanding pathogenesis in schistosomiasis as TNF-alpha plays a crucial role
      in circumoval granuloma formation and adversely affects schistosome fecundity.

PMID- 11594792
TI  - Plasma proinflammatory cytokine response to surgical stress in elderly patients.
AB  - We investigated the change of plasma cytokines concentrations in elderly patients
      during lower abdominal surgery. Plasma interleukin (IL-)6 concentrations (68.0+/
      15.4 and 36.1+/-20.7 pg/ml) in elderly patients at 24 h and at 3 days after
      surgery were significantly higher than those (35.1+/-21.5 and 18.6+/-10.6 pg/ml)
      of young adults. Plasma IL-6 concentrations (92.3+/- 31.9 pg/ml) in elderly
      patients anesthetized with propofol and fentanyl were significantly higher at the
      end of the operation than that (57.9+/-36.7 pg/ml) of elderly patients
      anesthetized with sevoflurane and fentanyl. In conclusion, elderly patients have
      an increased and delayed IL-6 response to surgical trauma compared with young
      adults. Plasma IL-6 production after surgical trauma in elderly patients with
      total intravenous anesthesia with propofol was significantly higher than that in
      elderly patients with sevoflurane anesthesia.

PMID- 11594793
TI  - Differential rates of cytokine production and apoptosis in venipuncture and
      finger-stab derived blood cultures.
AB  - The collection of finger-stab (FS) blood is a convenient and non-invasive method
      of rapidly acquiring human blood and is becoming increasingly popular for use in
      human biomonitoring studies. This study compared whole blood (WB) and peripheral
      blood mononuclear cell (PBMC) cultures derived from venipuncture (VP) and FS
      blood, to determine whether they respond similarly under culture conditions. The
      rates of spontaneous- and radiation-induced apoptosis and pro-inflammatory
      cytokine production were monitored over 72 h in each of four culture conditions.
      In non-irradiated WB cultures, the spontaneous rate of apoptosis was
      significantly lower in cultures from FS-derived blood than from VP-derived blood.
      However, FS- and VP-derived cultures responded similarly to radiation-induced
      apoptosis. PBMC cultures, regardless of the source, were the most responsive to
      radiation. When the levels of pro-inflammatory cytokines were measured, a
      significant time-dependent increase in TNF-alpha, IL-6 and IL-1beta production
      was observed in FS-derived cultures, but not in VP-derived cultures. While VP and
      FS blood cultures were found to respond similarly to radiation-induced apoptosis,
      there was a significant difference in the rate of spontaneous apoptosis in non
      irradiated WB cultures and in the in situ production of pro-inflammatory
      cytokines between VP- and FS-derived blood cultures.

PMID- 11594795
TI  - A20 inhibits NF-kappa B activation downstream of multiple Map3 kinases and
      interacts with the I kappa B signalosome.
AB  - A20, a TNF inducible gene, inhibits TNF-mediated apoptosis as well as NF-kappa B
      induced by this cytokine. Reporter assay experiments revealed that A20 is a very
      effective inhibitor of NF-kappa B signaling induced by TRAFs and several Map3
      kinases, including NIK, MEKK1, COT, and TAK1. Similarly, the NF-kappa B inducing
      activity of TAX, an activator of the I kappa B kinase complex, is also abrogated
      by A20. Inhibition of NF-kappa B is specific as A20 has no effect on TNF-alpha
      induced JNK activation. These results suggest that the molecular target of A20 is
      more distal to the receptor than TRAFs as previously proposed. A20 inhibits NF
      kappa B-dependent transcription without a concomitant decrease in nuclear NF
      kappa B DNA binding activity or nuclear translocation of p65. This apparent
      discrepancy between transcriptional readout and gel shift experiments is observed
      with a variety of stimuli, including expression of IKK beta. Therefore, in
      addition to the phosphorylation of I kappa B, another signal is needed for
      transcriptional activation of NF-kappa B. A20 inhibits this non-redundant signal.
      The observation that A20 associates with IKK alpha and is phosphorylated upon IKK
      beta co-expression may suggest that A20 interferes with some aspects of
      signalosome function.

PMID- 11594796
TI  - Granulocyte colony-stimulating factor induces neutrophils to secrete macrophage
      colony-stimulating factor.
AB  - In this work we provide evidence showing that granulocytes produce macrophage
      colony-stimulating factor (M-CSF) from the band cell stage and secrete this
      factor when induced to differentiate into polymorphonuclear cells by recombinant
      human granulocyte colony-stimulating factor (rhG-CSF). Using an enriched
      population of myeloid band cells from murine bone marrow, we identified the
      presence of M-CSF with a chromophore-labelled monoclonal anti-M-CSF antibody.
      Using ELISA we detected the secretion of M-CSF in the supernatants of cultures of
      enriched band cells when induced with rhG-CSF to differentiate into mature
      neutrophils. We also found that M-CSF is the only factor responsible for the
      colony forming activity in the supernatants and lysates of band cells treated
      with rhG-CSF.

PMID- 11594798
TI  - Amyotrophic lateral sclerosis: evidence for intact hepatocyte growth factor/met
      signalling axis.
AB  - Hepatocyte growth factor (HGF) is a secreted cytokine which is expressed in the
      central nervous system (CNS) together with its specific receptor MET. Since HGF
      exerts strong neurotrophic activity including motoneurons, we have further
      analysed whether the HGF/MET axis is defective in patients with amyotrophic
      lateral sclerosis (ALS). Intrathecal HGF-secretion was measured in cerebrospinal
      fluid (CSF) from patients with amyotrophic lateral sclerosis and in controls
      without neurological diseases using a specific sandwich immunoassay (ELISA). MET
      expression was analysed by immunohistology in spinal cord cross-sections of ALS
      patients and unaffected controls. The HGF concentrations in CSF were moderately
      but significantly increased in ALS patients compared to healthy controls (580
      pg/ml vs 348 pg/ml). MET-protein was detectable in spinal cord motoneurons of
      patients with ALS as well as unaffected controls. The data demonstrate that ALS
      does not show a lack of the trophic signalling axis, HGF/MET, suggesting that the
      signalling system itself is not affected. The moderate increase in HGF-secretion
      may represent a compensatory effect.

PMID- 11594797
TI  - Evaluation of cytokine toxicity induced by vaccinia virus-mediated IL-2 and IL-12
      antitumour immunotherapy.
AB  - Single intratumoural treatment of nude mice with a vaccinia virus (VV)-expressing
      interleukin-1 (IL-2) or IL-12 induced significant tumour growth inhibition
      associated with clear signs of toxicity. At a low virus dose, only some treated
      animals showed signs of toxicity. We characterized and compared the activity of
      NK and B cells and major pro-inflammatory factors (IFN-gamma, TNF-alpha) in
      treated animals with and without toxicity. One week after treatment animals
      exhibiting signs of cytokine-related toxicity showed dramatic increases in
      several measured parameters. High leukocyte and lymphocyte counts in blood and
      marked increases in NK and CD25(+)cells in both blood and spleen were associated
      with IL-2-induced toxicity, while IL-12-induced toxicity was related to a great
      elevation of CD25(+)cells in blood and CD71(+)cells in the spleen. In contrast,
      immune activation in animals free of toxicity was observed on day 2 after the
      treatment, which drastically declined by day 7. Thus, immune responses induced by
      IL-2 and IL-12 therapy appear to play important roles in both tumour inhibition
      and the accompanying toxicity. Short-term effects induced by IL-2 and IL-12 could
      be critical for antitumour therapy that prolongs survival and protects from
      adverse side effects.

PMID- 11594799
TI  - Effect of midazolam on interleukin-6 mRNA expression in human peripheral blood
      mononuclear cells in the absence of lipopolysaccharide.
AB  - Midazolam, a benzodiazepine, has an hypnotic effect via benzodiazepine receptors
      and is widely used as an anaesthetic. Recently, it has been suggested that
      benzodiazepines modulate cytokine responses. The purpose of the present study was
      to evaluate the effect of midazolam on interleukin-6 (IL-6) response by observing
      mRNA expression levels in human peripheral blood mononuclear cells (PBMCs) in the
      absence of lipopolysaccharide (LPS). PBMCs were isolated from healthy volunteers
      in endotoxin-free 0.9% sodium chloride solution. The cells were incubated for 2 h
      at 37 degrees C immediately after isolation. IL-6 mRNA expression levels in the
      cells were quantified using reverse transcription and competitive polymerase
      chain reaction. It was found that midazolam time-dependently inhibited the IL-6
      mRNA expression in PBMCs in the absence of LPS, and significantly inhibited the
      IL-6 mRNA expression at 1 microg/ml (P<0.05) or 10 microg/ml (P<0.01) in the
      absence of LPS. However, neither a specific agonist of peripheral-type
      benzodiazepine receptors, Ro5-4864, nor a specific agonist of central-type
      benzodiazepine receptors, clonazepam, inhibited IL-6 mRNA expression. These
      findings indicated a suppression of the IL-6 response in human PBMCs by midazolam
      in the absence of LPS, and suggests that midazolam has its effect not via
      benzodiazepine receptors, but by another mechanism.

PMID- 11594800
TI  - Regulation and role of interleukin 6 in wounded human epithelial keratinocytes.
AB  - Dermal wounding is accompanied by inflammation and the resulting proinflammatory
      cytokines, including interleukin (IL)-6, are thought to play an important role in
      the repair process. IL-6 is produced by normal human keratinocytes to various
      dermatological diseases and we have recently shown it is also required for normal
      wound repair. However, neither the events responsible for its induction nor its
      role in repair have been clearly identified. Using a recently developed in vitro
      wounding model, we demonstrate that IL-6 mRNA is expressed and immunoreactive IL
      6 is released from cultures of human epidermal keratinocytes (NHEKs) following
      wounding. The transcription factors, NF kappa B and NF-IL-6 (C/EBP beta), which
      coordinately help regulate IL-6 expression, were activated following wounding and
      preceded the appearance of IL-6. Addition of IL-1 alpha to NHEK cultures
      increased IL-6 production and activated NF kappa B and C/EBP beta. Addition of
      the IL-1 alpha receptor antagonist inhibited both IL-6 mRNA expression and the
      transcription factors following wounding. Immunoreactive IL-1 alpha was detected
      in the medium following wounding in the absence of new message. Furthermore,
      addition of IL-6 to NHEK cultures decreased the expression of keratins 1 and 10,
      differentiation markers of keratinocytes, while proliferation was not affected.
      Taken together, these data indicate that constitutive keratinocyte-derived IL-1
      alpha is a stimulus for IL-6 production in wounded epidermis, the response
      involves NF kappa B and C/EBP beta transcription factors, and IL-6 may be
      associated with modulation of keratinocyte differentiation rather than
      proliferation.

PMID- 11594801
TI  - An efficient, scalable synthesis of the molecular transporter octaarginine via a
      segment doubling strategy.
AB  - [reaction: see text]. Short oligomers of arginine function as remarkably
      efficient molecular transporters of drugs and probe molecules into cells and
      tissue. Currently, these compounds are prepared on resin through a unidirectional
      solid-phase synthesis. To extend the utility of these compounds for therapeutic
      and research applications, a scalable solution-phase synthesis of Arg8 (1) has
      been developed on the basis of a segment doubling strategy that proceeds in 13
      steps and 28% overall yield from 4, including a novel one-step perdeprotection
      perguanidinylation reaction.

PMID- 11594802
TI  - T(h)-symmetrical N8(C=C)6 and P8(C=C)6; an extraordinary contrast in
      heterofullerene stability.
AB  - [structure: see text]. T(h)-symmetrical P8(C=C)6, 1, is predicted to be a
      remarkably stable small heterofullerene with carbon atoms less pyramidal than in
      C60. T(h)-N8(C=C)6, 2, in sharp contrast, is strongly destabilized relative to
      T(h)-(HC)8(C=C)6. The causes of this extraordinarily large difference (nearly
      1000 kJ x mol(-1) between 1 and 2 are explained.

PMID- 11594803
TI  - A short and efficient route to novel scyphostatin analogues.
AB  - [structure: see text]. Several novel scyphostatin analogues have been prepared in
      up to 18% yield over five steps from commercially available 4-bromoguaiacol,
      utilizing an organometallic addition to afford the desired syn-hydroxy-epoxides.

PMID- 11594804
TI  - Stereoselective hydrocoupling of [(1R)-exo]-3-exo-(diphenylmethyl)bornyl
      cinnamates by electroreduction.
AB  - [reaction: see text]. The chiral auxiliary [(1R)-exo]-3-exo
      (diphenylmethyl)borneol, synthesized from (1R)-(+)-camphor in three steps, was
      highly effective for the stereoselective hydrocoupling of its cinnamates by
      electroreduction. From the resulting hydrodimers, (3R,4R)-3,4-diaryladipic acid
      esters and (3R,4R)-3,4-diarylhexane-1,6-diols were synthesized in 87-95% ee.

PMID- 11594805
TI  - Intramolecular conjugate addition of alkenyl and aryl functions to enones
      initiated by lithium-iodine exchange.
AB  - [reaction: see text]. Treatment of each of the substrates 20-26, 29, and 46-48
      with t-BuLi in THF, in the presence of HMPA and TMSCl, provides good-to-excellent
      yields of the intramolecular conjugate addition products 30-36, 37, and 49-51,
      respectively.

PMID- 11594806
TI  - Alkylation of chiral alpha-hydroxy ketones derived from (1R)-(+)-camphor. An
      asymmetric variant of the classical acetylene route to carbonyl compounds.
AB  - [reaction: see text]. The asymmetric version of the traditional route for
      transforming acetylene into alpha-branched carbonyl compounds is now feasible for
      the first time. The method involves the temporary attachment of camphor to
      acetylene and gives a remarkably high diastereo- and enantioselectivity.

PMID- 11594807
TI  - A convenient and asymmetric protocol for the synthesis of natural products
      containing chiral alkyl chains via Zr-catalyzed asymmetric carboalumination of
      alkenes. Synthesis of phytol and vitamins E and K.
AB  - [reaction: see text]. A convenient and asymmetric protocol for the synthesis of
      chiral oligoisoprenoids is described. Typically, a C14 vitamin E side chain 5 was
      synthesized in 47% yield over four steps. Isomeric purity of 5 was upgraded to
      >99% R at C-2 and 97% R at C-6 by the statistical formation of stereoisomeric p
      phenylenebisurethanes and their diastereomeric separation. In addition, phytol
      and vitamin K were synthesized in 21% and 28% overall yields, respectively, over
      five steps from 1.

PMID- 11594809
TI  - N-(2-methoxycarbonyl-2-yloethyl) (3-nitrenophenyl)aminyl: EPR observation of a
      quintet hetero-spin molecule.
AB  - [reaction: see text]. The EPR observation of a ground-state quintet hetero-spin
      molecule, N-(2-methoxycarbonyl-2-yloethyl) (3-nitreno-phenyl)aminyl 3, in a MTHF
      matrix at cryogenic temperatures is reported. The molecule has two different
      kinds of triplet sites, and the ZFS parameters of the quintet are /D/hc/ = 0.170
      cm(-1) and /E/hc/ = 0.004 cm(-1). As a result of the nature of the 1,3-localized
      biradical, the quintet 3 was thermally labile over 5 K.

PMID- 11594808
TI  - Unprecedented oxidation of a phenylglycinol-derived 2-pyridone: enantioselective
      synthesis of polyhydroxypiperidines.
AB  - [reaction: see text]. The phenylglycinol-derived 2-pyridone 1 undergoes m-CPBA
      oxidation steroselectively leading to the chiral nonracemic unsaturated bicyclic
      hydroxylactam 2, from which the enantioselective synthesis of (3R,5R)-3,4,5
      trihydroxypiperidine (16) and the formal synthesis of the azasugar epiisofagomine
      are described. The enantioselective synthesis of (S)-N-Boc-3-hydroxypiperidine
      and (3R,4S)-3,4-dihydroxypiperidine is also reported.

PMID- 11594810
TI  - Chemoenzymatic iterative synthesis of difficult linkages of oligosaccharides on
      soluble polymeric supports.
AB  - [reaction: see text]. A trisaccharide donor containing a cis-Galpalpha(1-->4)Galp
      linkage was prepared using a synthetic strategy based on chemoenzymatic
      oligosaccharide synthesis on a soluble polymeric support. Significantly, only
      retaining glycosyltransferases gave complete reactions, whereas inverting enzymes
      showed little or no activity with poly(ethylene glycol) (MPEG)-bound lactose as
      an acceptor. The MPEG-attached trisaccharide was shown to bind to Verotoxin-1 by
      transfer NOE studies through the Galpalpha(1-->4)Galp portion of the molecule.

PMID- 11594811
TI  - Regioselective and enantiospecific rhodium-catalyzed allylic amination with N
      (arylsulfonyl)anilines.
AB  - [reaction: see text]. The regioselective and enantiospecific rhodium-catalyzed
      allylic amination of secondary allylic carbonates 1 with N-(arylsulfonyl)anilines
      provides a convenient process for the construction of arylamines 2. This method,
      in conjunction with ring-closing metathesis and radical cyclization reactions,
      allows the direct construction of biologically relevant pharmacophores as
      exemplified by the construction of dihydroquinoline and dihydrobenzo[b]indoline
      derivatives.

PMID- 11594812
TI  - First stereocontrolled synthesis of (S)-cleonin and related cyclopropyl
      substituted amino acids.
AB  - [reaction: see text]. Enantiomerically pure (S)-cleonin, a key component of the
      antitumor antibiotic cleomycin, was prepared starting from (R)-serine. The
      Kulinkovich cyclopropanation of the methyl ester of N-Cbz serine acetonide gave
      the hydroxycyclopropyl moiety. The amino alcohol region was further oxidized to
      amino acid. The Kulinkovich cyclopropanation allowed also the preparation of
      other non-natural substituted cyclopropylglycines.

PMID- 11594813
TI  - A new fluorescent chemosensor for copper ions based on tripeptide glycyl-histidyl
      lysine (GHK).
AB  - [structure: see text]. A new fluorescent chemosensor for Cu2+ ions was
      synthesized by modifying the tripeptide glycyl-histidyl-lysine (GHK) with 9
      carbonylanthracene via the standard Fmoc solid-phase peptide synthesis method.
      While significant fluorescence quenching was observed from the molecule upon
      binding with Cu2+, addition of Fe2+, Co2+, Ni2+, and Zn2+ to the peptide solution
      caused a minimum fluorescence emission spectral change, indicating a high
      specificity of this chemosensor for Cu2+ ions. Effects of pH were also
      investigated.

PMID- 11594814
TI  - Stereoselective synthesis of functionalized trisubstituted olefins via
      palladium(0)-catalyzed cross-coupling reaction.
AB  - [reaction: see text]. A highly flexible and stereoselective protocol for the
      synthesis of branched (E)- and (Z)-trisubstituted alkenes has been developed. The
      key steps are hydrozirconation-iodination of (1-alkynyl)trimethylsilane followed
      by Negishi-type cross-coupling. The resultant (Z)-vinyl silane is iododesilylated
      and subjected to a second cross-coupling reaction to give the trisubstituted
      olefin. Model studies aimed at the construction of the C14-C15 (Z)-trisubstituted
      olefin of discodermolide and the C8-C9 (Z)-trisubstituted olefin of callystatin A
      and analogues are also described.

PMID- 11594815
TI  - A ring-closing metathesis strategy to phosphonosugars.
AB  - [reaction: see text]. Syntheses of cyclic phosphonate (phostone) analogues of
      carbohydrates containing a phosphorus atom at the anomeric position are
      described. The ring-closing metathesis reaction of mixed allylic phenyl esters of
      allylphosphonic acid 2 and 22 generates the six-membered allylic phosphonates 3
      and 23 in excellent yields. Introduction of the polyhydroxy functionality in
      these cyclic phosphonates provides facile entry into an array of phostone sugar
      analogues.

PMID- 11594816
TI  - Double cationic propargylation: from linear to polycyclic ethers.
AB  - [reaction: see text]. The trapping of cations generated from Co2(CO)6
      bispropargylic alcohols provided diethers in good yield. The procedure is also
      valid when two vicinal acetylenes are present. The methodology can be applied to
      the synthesis of symmetrical or unsymmetrical linear or cyclic propargylic
      ethers. The use of substrates with a stereochemically defined secondary
      nucleophilic alcohol provided cyclic ethers with a high degree of stereocontrol.

PMID- 11594818
TI  - A novel one-pot pyrrole synthesis via a coupling-isomerization-Stetter-Paal-Knorr
      sequence.
AB  - [reaction: see text]. 1,2,3,5-tetrasubstituted pyrroles can be synthesized in
      good yields in a one-pot, three-step, four-component process by a coupling
      isomerization-Stetter reaction-Paal-Knorr sequence of an electron-poor
      (hetero)aryl halide, a terminal propargyl alcohol, an aldehyde, and a primary
      amine. The structures of the 1,4-diketone 4f and the pyrrole 6b were additionally
      supported by X-ray structure analyses.

PMID- 11594817
TI  - Enantioselective synthesis of spiropentanes from hydroxymethylallenes.
AB  - [reaction: see text]. Hydroxymethylallenes are efficiently converted to the
      corresponding spiropentanes in high yields and enantiomeric ratios upon treatment
      with Zn(CH2I)2 and dioxaborolane ligand 1. The reaction also proceeds with
      complete diastereocontrol. The application of this methodology to the synthesis
      of spiropentaneacetic acid is also presented.

PMID- 11594819
TI  - Atom-economical synthesis of the N(10)-C(17) fragment of cyclotheonamides via a
      novel Passerini reaction-deprotection-acyl migration strategy.
AB  - [reaction: see text]. A novel variant of the atom-economical Passerini reaction
      between suitably protected argininal, dipeptide isonitrile, and proline
      components afforded adduct 13. Orthogonal N-deprotection of 13 led, via a smooth
      O- to N-acyl migration, to 14, which constitutes the N(10)-C(17) fragment of the
      cyclotheonamide family of serine protease inhibitors. Each reaction in this three
      step protocol proceeds in good yield and under very mild conditions.

PMID- 11594820
TI  - Long-range magnetic interactions in trans-1,4-cyclohexylene- and 1,3-adamantylene
      bis(p-nitrenylbenzene) by pi-sigma-pi hyperconjugation.
AB  - [structure: see text]. Di(phenylnitrene)s linked with trans-1,4-cyclohexylene (3)
      and 1,3-adamantylene (4) units were generated photochemically at cryogenic
      temperatures. The EPR spectra are attributed to quintets. The temperature
      dependence of the signal intensities indicates that both quintets are thermally
      accessible states with energy gaps DeltaE(S-Q) = 138 and 300 J x mol(-1),
      respectively. DFT calculations showed that the magnetic interactions originated
      in the pi-sigma-pi hyperconjugative through-bond interactions.

PMID- 11594821
TI  - Enantioselective ring cleavage of dioxane acetals mediated by a chiral Lewis
      acid: application to asymmetric desymmetrization of meso-1,3-diols.
AB  - [reaction: see text]. Phenylalanine-derived B-aryl-N-tosyloxazaborolidinones
      selectively activate one of two enantiotopic oxygen atoms in prochiral anti
      dioxane acetals derived from meso-1,3-diols, leading to enantioselective
      formation of ring-cleavage products. The reaction is utilized as a key step in
      asymmetric desymmetrization of meso-1,3-diols.

PMID- 11594822
TI  - Mizoroki-Heck type reaction of organoboron reagents with alkenes and alkynes. A
      Pd(II)-catalyzed pathway with Cu(OAc)2 as an oxidant.
AB  - [reaction: see text]. In contrast to the Pd(0)-catalyzed mechanism by Uemura,
      Mizoroki-Heck type reaction of boronic acids is found to proceed under a Pd(II)
      mediated pathway using a catalytic amount of Pd(OAc)2 in the presence of Cu(OAc)2
      as an oxidant. Treatment of a variety of alkenes with boronic acids, boronates,
      and sodium tetraphenylborate furnishes beta-arylated and alkenylated products in
      good to excellent yields. The reactions with norbornene, norbornadiene, and
      diphenylacetylene are also performed to give 1:2 or 2:1 coupling products.

PMID- 11594823
TI  - High enantiocontrol in the intramolecular cyclopropanation of diazo ketones
      catalyzed by dirhodium(II) complexes with ortho-metalated aryl phosphine ligands.
AB  - [reaction: see text]. Chiral dirhodium(II) complexes, Rh2(O2CCF3)2(PC)2, [PCH =
      (p-CH3C6H4)3P, (m-CH3C6H4)3P], provide an excellent yield and a high
      enantiocontrol in the cyclopropanation of alpha-diazo ketones with gamma and
      delta double bonds. The ee values are significantly dependent on the solvent
      used; the best results are obtained using pentane.

PMID- 11594824
TI  - A new, chiral bis-benzothiazine ligand.
AB  - [reaction: see text]. The synthesis and application of a new, chiral bis
      benzothiazine ligand are described.

PMID- 11594825
TI  - The Diels-Alder reactions of quinone imine ketals: a versatile synthesis of
      highly substituted 5-methoxyindoles.
AB  - [reaction: see text]. N-benzoylated quinone imine ketals undergo smooth
      cycloadditions in a [4 + 2] sense to yield the expected cycloadducts. The crude
      cycloadducts, when subjected to a short series of simple transformations, produce
      synthetically useful quantities of 5-methoxyindoles in excellent overall yields.

PMID- 11594826
TI  - Chiral phosphine-free Pd-mediated asymmetric allylation of prochiral enolate with
      a chiral phase-transfer catalyst.
AB  - [reaction: see text]. A chiral phase-transfer catalyst has been applied to the
      asymmetric allylation of the tert-butyl glycinate-benzophenone Schiff base with
      various allylic acetates for the first time to give the allylated products in
      good yields and with comparable to higher enantioselectivity than for asymmetric
      alkylation at the same temperature (91-96% ee) without any chiral ligands for
      coordinating to the palladium.

PMID- 11594827
TI  - Dimyristoylated peptides incorporated into liposomes are polyvalent fertilin beta
      mimics.
AB  - [structure: see text]. Fertilin beta is an integral membrane sperm protein that
      is involved in sperm binding to the egg plasma membrane. We synthesized a
      dimyristoylated fertilin beta peptide and incorporated it into POPC liposomes at
      1 mol %. The concentration of fertilin beta peptide required for 50% inhibition
      is reduced 100-fold to 5.2 +/- 1.6 microM relative to a monomeric control.
      Moreover, in contrast to the inhibition observed with monomeric peptides, we
      obtain complete inhibition with the peptidic liposomes.

PMID- 11594828
TI  - (2-methoxyphenyl)dimethylsilyl lithium and cuprate reagents offer unique
      advantages in multistep synthesis.
AB  - [structure: see text]. The new silyllithium reagent 1 and the corresponding
      cyanocuprate 3 are readily generated under optimal conditions and are useful for
      the formation of C-Si bonds. Tamao-Fleming oxidation of such C-Si bonds can be
      effected under very mild conditions.

PMID- 11594829
TI  - Traceless solid-phase synthesis of 1,2,4-triazoles using a novel amine resin.
AB  - [reaction: see text]. A solid-phase route to 5-aryl-3-arylthiomethyl-1,2,4
      triazoles has been developed that permits the incorporation of two elements of
      diversity. The heterocycle was constructed upon a novel 4-benzyloxy-2
      methoxybenzylamine (BOMBA) resin, from which traceless cleavage could be effected
      with dilute TFA. A library of 96 triazoles was produced with an average yield of
      26% (84% yield per step) and an average purity of 80%. In a direct comparison,
      the new BOMBA resin proved to be markedly superior to Rink Amide resin for this
      application.

PMID- 11594830
TI  - Nickel-promoted alkylative or arylative carboxylation of alkynes.
AB  - [reaction: see text]. Nickel-promoted alkylative or arylative carboxylation of
      terminal alkynes via a carbon dioxide fixation process was investigated. In the
      presence of a stoichiometric amount of a zero-valent nickel complex, the reaction
      of alkynes with CO2 gave a nickelacycle, which was reacted with various
      organozinc reagents under very mild conditions to provide beta,beta'
      disubstituted, alpha,beta-unsaturated carboxylic acids in a highly regio- and
      stereoselective manner.

PMID- 11594831
TI  - Intramolecular electrophilic aromatic substitution reactions of 2-amidoacroleins:
      a new method for the preparation of tetrahydroisoquinolines, tetrahydro-3
      benzazepines, and hexahydro-3-benzazocines.
AB  - [reaction: see text]. A variety of heterocyclic ring systems can be prepared by
      subjecting N-aryl-substituted 5-amido-1,3-dioxins to Lewis acids. The reactions
      proceed via catalyzed retrocycloadditions to afford 2-amidoacroleins and
      concomitant regioselective electrophilic aromatic substitution reactions. The
      transformation is also successful using dioxins with amides that are within the
      incipient ring to afford the analogous lactams.

PMID- 11594832
TI  - Novel synthesis of the glycosidase inhibitor deoxymannojirimycin and of a
      synthetic precursor D-lyxo-hexos-5-ulose.
AB  - [reaction: see text]. The synthesis of D-lyxo-hexos-5-ulose (5-ketomannose, 1,5
      dicarbonyl sugar), a synthetic precursor to the glycoprocessing inhibitor
      deoxymannojirimycin, was carried out by an in situ epoxidation and hydrolysis of
      a trimethylsilyl-protected 6-deoxyhex-5-enopyranoside followed by facile removal
      of the protecting groups. A novel nine-step synthesis of deoxymannojirimycin has
      also been achieved from methyl alpha-D-mannopyranoside; this involved
      methanolysis of epoxides derived from an acetylated 1-azido-6-deoxyhex-5
      enopyranoside followed by deprotection and catalytic hydrogenation.

PMID- 11594833
TI  - Practical asymmetric synthesis of a selective endothelin A receptor (ETA)
      antagonist.
AB  - [structure: see text]. A practical, chromotography-free asymmetric synthesis was
      developed for the large scale preparation of an endothelin receptor antagonist 2.
      This synthesis includes a new efficient process for the preparation of 6-bromo
      2,3-dihydrobenzofuran, a stereoselective conjugate addition of an aryllithium
      followed by stereospecific addition of the Grignard reagent of the top aryl
      bromide, and an aminophosphate-mediated sterospecific intramolecular enolate
      alkylation, which led to the formation of the five-membered ring bearing three
      contiguous asymmetric centers.

PMID- 11594834
TI  - An unexpected Paterno-Buchi reaction in the crystalline state.
AB  - [reaction: see text]. The solution and solid-state photochemistry of a series of
      aryl 1-phenylcyclopentyl ketones (1) was investigated. While typical Norrish type
      I products were formed in solution, irradiation of crystals of 1 afforded the
      novel oxetanes 3 and 4 regiospecifically. The formation of the oxetanes is
      believed to occur through Norrish type I cleavage and hydrogen abstraction,
      producing an alkene and an aldehyde, followed by a Paterno-Buchi reaction within
      the crystal lattice cage.

PMID- 11594835
TI  - Commercially available 5'-DMT phosphoramidites as reagents for the synthesis of
      vinylphosphonate-linked oligonucleic acids.
AB  - [reaction: see text]. Commercially available cyanoethyl phosphoramidites derived
      from T, d(C), d(A), and d(G) were hydrolyzed (1H-tetrazole, MeCN/H2O) to give the
      corresponding H-phosphonates in excellent yields. Palladium(0)-catalyzed cross
      coupling of each of these with the thymidine-derived vinylbromide 2 afforded the
      corresponding vinylphosphonate-linked dimers TT, d(C)T, d(A)T, and d(G)T in
      modest to good yields. The TT dimer was further elaborated to give a 5'-DMT-TT-3'
      CEP building block, and this was used in the automated synthesis of the TpTTpT
      tetramer.

PMID- 11594836
TI  - Lipase-mediated resolution of 4-TMS-3-butyn-2-ol and use of the mesylate
      derivatives as a precursor to a highly stereoselective chiral allenylindium
      reagent.
AB  - [reaction: see text]. An improved procedure for the resolution of 4
      trimethylsilyl-3-butyn-2-ol has been developed. The mesylate derivatives of the
      resolved alcohols have been found to undergo highly enantio-, regio-, and
      diastereoselective additions to aldehydes, leading to homopropargylic alcohol
      adducts.

PMID- 11594837
TI  - Compatibility of the thioamide functional group with beta-sheet secondary
      structure: incorporation of a thioamide linkage into a beta-hairpin peptide.
AB  - [structure: see text]. We report the incorporation of a thioamide linkage between
      the i + 2 and i + 3 residues of the type II' beta-turn of a peptide known to fold
      into a beta-hairpin conformation. Two-dimensional NMR spectroscopy and circular
      dichroism spectroscopy indicate that the thioxo peptide adopts a hairpin
      conformation similar to that of the oxo peptide and that the hairpin conformation
      persists at elevated temperatures. The results show that a thioamide linkage is
      compatible with beta-sheet secondary structure.

PMID- 11594838
TI  - A convenient method for 3-pyrroline synthesis.
AB  - [reaction: see text]. The synthesis of a range of 3-pyrrolines has been achieved
      from primary amine starting materials using a two-step alkylation/alkylidene
      carbene CH-insertion reaction sequence. We have shown that insertion into a range
      of CH-bond types is possible, and the formation of nitrogen-bearing quaternary
      stereocenters is a relatively facile process. The insertion reaction occurs with
      >95% retention of stereochemistry, but the presence of protecting groups on
      nitrogen is generally deleterious to the cyclization process.

PMID- 11594839
TI  - Facile enantiodivergent approach to 5-hydroxy-5,6-dihydro-2(1H)-pyridones. First
      total synthesis of both enantiomers of pipermethystine.
AB  - [reaction: see text]. A novel enantiodivergent approach to 5-hydroxy-5,6-dihydro
      2(1H)-pyridones using a ring closing metathesis and a lipase-mediated kinetic
      resolution as key steps is described and applied to the first synthesis of both
      enantiomers of pipermethystine.

PMID- 11594840
TI  - A new entry to oxacycles via base-catalyzed endo mode cyclization of allenyl
      sulfoxides and sulfones.
AB  - [reaction: see text]. Treatment of the allenyl sulfoxides and sulfones possessing
      a proper delta-hydroxy appendage at the C-1 position with potassium tert-butoxide
      effected endo mode ring closure at the sp-hybridized carbon center of the allenyl
      moiety to provide the five- to eight-membered oxacycles in high yields.

PMID- 11594841
TI  - Synthesis and reactivity of silyl vinylketenes: a formal interrupted Dotz
      benzannulation with unexpected silyl migration.
AB  - [reaction: see text]. An efficient method for the generation of silyl
      vinylketenes from the thermal reaction of Fischer carbene complexes with silyl
      substituted phenylacetylenes is described. Although the silyl vinylketene
      products are highly stable, conditions have been identified to induce a
      benzannulation/silyl migration process, providing aromatic silyl ethers.

PMID- 11594842
TI  - Beta-selective glycosylations with masked D-mycosamine precursors.
AB  - [reaction: see text]. Both an intramolecular aglycon delivery (IAD) method and an
      intermolecular S(N)2 displacement method were examined for beta-selective
      glycosylations of cholesterol with D-mycosamine. An anomeric sulfoxide, sulfide,
      selenide, and fluoride were all successfully used as glycosyl donors in IAD
      reactions. The alpha-bromo ketone 19 was synthesized from protected mycosamine
      and employed in an intermolecular S(N)2 glycosylation reaction. Both routes were
      successful for the model alcohol, cholesterol.

PMID- 11594843
TI  - Free radical reactions on soluble supports from ring-opening metathesis.
AB  - [reaction: see text]. Free radical reactions were performed on soluble ring
      opening metathesis (ROM) polymers. These polymers have high substrate loading,
      short reaction times, and the benefit of a facile purification. All reactions on
      these supports were obtained in good yields as white crystalline-like materials
      readily separated from tin byproducts.

PMID- 11594844
TI  - Substituted alkenediols by alkylative double ring opening of dihydrofuran and
      dihydropyran epoxides.
AB  - [reaction: see text]. Dihydrofuran and dihydropyran epoxides undergo alkylative
      double ring opening with organolithiums to provide a new route to substituted
      alkenediols.

PMID- 11594845
TI  - 1,4-pentadienyl-3-sulfonamides: frameworks for "disfavored" radical cascade
      cyclizations.
AB  - [reaction: see text]. 1,4-pentadienyl-3-sulfonamides afford products including
      those resulting from disfavored 5-endo-trig reactions when subjected to radical
      cyclization conditions. Products resulting from pathways featuring 4-exo-trig
      cyclizations are also detected, even when the 4-exo-trig reaction leads to a
      highly strained bicyclo[3.2.0] ring system.

PMID- 11594846
TI  - An enantioselective strategy to macrocyclic bisindolylmaleimides. An efficient
      formal synthesis of LY 333531.
AB  - [reaction: see text]. The ability to employ a bromo alcohol as a nucleophile in a
      palladium-catalyzed dynamic kinetic asymmetric transformation leads to an
      efficient synthesis of a selective PKC inhibitor under clinical development.

PMID- 11594847
TI  - Dynamic NMR studies of a potential chiroptical switch based on dithiocarbamate
      iminodithiolane interconversion.
AB  - [reaction: see text]. Variable temperature NMR spectra of the chiral spiro[(4-N,N
      dimethyldithiocarbamato)-(2-N,N-dimethylimino)-1,3-dithiolane-5,9'-xanthene] show
      complex dynamics including degenerate interconversion of the dithiocarbamate and
      iminodithiolane groups. The rate of this switching process can be controlled by
      chemical modification: the analogous spiro[dithiolane-fluorene] derivative shows
      no interconversion. These novel materials have potential application as molecular
      switching elements in information storage devices.

PMID- 11594849
TI  - Highly chemo-, diastereo-, and enantioselective reduction of 1,2-dialkyl-3-aryl
      1,3-diketones for preparation of aldol-type compounds.
AB  - [reaction: see text]. Highly chemo-, diastereo-, and enantioselective borohydride
      reduction of 2-substituted-1,3-diketones was achieved in the presence of the
      optically active beta-ketoiminato cobalt complex catalysts to afford the
      optically active 2-substituted-3-hydroxyketones. The present catalytic and
      enantioselective reduction could provide an alternative potential for preparation
      of optically active anti-aldol-type compounds.

PMID- 11594848
TI  - New ammonia equivalents for the Pd-catalyzed amination of aryl halides.
AB  - [reaction: see text]. LiN(SiMe3)2, Ph3SiNH2, and LiNH2 can be be used as ammonia
      equivalents for the Pd-catalyzed coupling of aryl halides. Using these amine
      derivatives, simple anilines, including ortho-substituted ones, as well as di-
      and triarylamines can be readily prepared.

PMID- 11594851
TI  - Debridement of necrotic eschar with 40% urea paste speeds healing of residual
      limbs and avoids further surgery.

PMID- 11594852
TI  - Too few or too many dermatologists? Difficulties in assessing optimal workforce
      size.
AB  - Discussions of the dermatology workforce have been dominated in the last 3
      decades by concerns of an impending surplus. The aim of this article is to
      provide new data on the supply of dermatologists and to reassess estimates of
      future demand in light of growing anecdotal evidence suggesting a shortage. The
      US supply of dermatologists has risen to 3.3 per 100 000 population, and this
      growing workforce continues to be geographically maldistributed. A number of
      factors, including a possible increase in the number of surgical and cosmetic
      procedures being performed, might make this growing supply less available for the
      care of medical dermatology patients, complicating any supply projections.
      Precise estimates of future demand are also difficult because changes in disease
      prevalence, medical technology, and the health care delivery system are not
      always predictable. In an era when regulatory bodies are making more centralized
      decisions about residency training, the field must attempt to estimate and
      anticipate future needs. Simply allowing others to make decisions about the
      future size of the workforce based on outdated data risks an oversupply or
      undersupply, either of which will have detrimental effects on dermatologists and
      their patients.

PMID- 11594853
TI  - Waiting times to see a dermatologist are perceived as too long by dermatologists:
      implications for the dermatology workforce.
AB  - BACKGROUND: The issue of workforce requirements in dermatology has come to
      attention in recent years because it affects the delivery of dermatologic care in
      the United States. OBJECTIVE: To determine the waiting times for appointments
      with dermatologists in order to assess the adequacy of the current level of
      dermatology workforce. METHODS: Waiting times were determined for new and return
      patient appointments by telephone survey of a random sample of American Academy
      of Dermatology members. Physicians' perception of the adequacy of the number of
      dermatologists in their area was used as a criterion standard to validate waiting
      times as a measure of workforce adequacy. Benchmark waiting times of 3 weeks for
      a new patient appointment and 2 weeks for a return appointment were established.
      RESULTS: Physicians' estimates of the waiting time for a new patient appointment
      and their perceptions of the adequacy of the number of practicing dermatologists
      in their area were closely correlated (r = -0.65; P<.001), validating the use of
      waiting times as a measure of workforce adequacy. More than 60% of the
      dermatologists surveyed exceeded the criterion cutoff waiting times, and more
      than 42% of the US population lives in areas underserved by dermatologists.
      Dermatologists practicing in areas of higher population density were more likely
      to have shorter waiting times for new patient appointments and were more likely
      to include cosmetic dermatology in their practices. CONCLUSION: The long waiting
      times for appointments suggests that the current supply of dermatologists is not
      adequate to meet the demand for dermatologists' services.

PMID- 11594854
TI  - Identification of clonal T cells in the blood of patients with systemic
      sclerosis: positive correlation with response to photopheresis.
AB  - OBJECTIVES: To search for circulating clonal T-cell populations in patients with
      systemic sclerosis (SSc), and to determine whether T-cell clonality in the blood
      predicts therapeutic response to photopheresis. DESIGN: Analysis of clonal T-cell
      receptor gamma gene rearrangements before photopheresis treatment and blinded
      clinical evaluation of cutaneous response to photopheresis in a case series.
      SETTING: University hospital setting. PATIENTS: Thirteen consecutive patients
      with SSc. INTERVENTIONS: Photopheresis in 11 patients. MAIN OUTCOME MEASURES:
      Clonality of T cells in the blood before photopheresis and clinical response to
      photopheresis. RESULTS: Screening of blood samples from 13 SSc patients for
      clonal T-cell receptor gamma gene rearrangements revealed a monoclonal T cell
      population in 6 (46%) of 13 SSc patients. Clinical response to photopheresis in
      11 patients was evaluated in a blinded manner using skin severity scores.
      Clonality of T cells appeared to be associated with a higher chance of response
      to photopheresis therapy, as 4 (67%) of 6 patients in the clone-positive group vs
      1 (20%) of 5 in the clone-negative group experienced a clinically significant
      response to treatment. CONCLUSIONS: A high proportion of patients with SSc have
      detectable expanded clonal T-cell populations in the peripheral blood, and such
      patients appear more likely to respond to photopheresis.

PMID- 11594856
TI  - Cutaneous field stimulation in the treatment of severe itch.
AB  - OBJECTIVE: To evaluate the efficacy of cutaneous field stimulation of C fibers
      for the treatment of itchy skin and its effect on peripheral nerve fibers as
      shown in skin biopsy specimens. DESIGN: We conducted an open-label uncontrolled
      study of 19 patients with itching. Each patient applied a flexible plate
      containing electrodes to the itchy area for 20 minutes at a time once daily for 5
      weeks to stimulate nerve fibers with a constant current (0.8 mA). Skin biopsy
      specimens were collected before treatment and at the end of treatment and were
      immunostained for calcitonin gene-related peptide and protein gene product 9.5.
      SETTING: University hospital in Lund, Sweden. PATIENTS: Sixteen patients with
      nostalgia paresthetica or brachioradial pruritus and 3 with generalized itch.
      INTERVENTIONS: Cutaneous field stimulation and punch biopsies of the itchy skin.
      MAIN OUTCOME MEASURES: Visual analog scale for assessment of itching and counting
      the immunoreactive nerve fibers in 3-mm biopsy specimens. RESULTS: Patients with
      localized itching experienced a reduction in mean values on the visual analog
      scale (from 78% before treatment to 42% by the end of the fifth week). The number
      of protein gene product 9.5- immunoreactive nerve fibers in the epidermis was
      reduced by 40% by the end of treatment compared with baseline values.
      CONCLUSIONS: Cutaneous field stimulation is an effective alternative for the
      treatment of localized itching. The reduction in itching is accompanied by
      degeneration of the epidermal nerve fibers, as evidenced by the loss of protein
      gene product 9.5 immunoreactivity.

PMID- 11594855
TI  - Evaluation of a silicone occlusive dressing after laser skin resurfacing.
AB  - BACKGROUND: Closed dressings are thought to promote postoperative wound healing
      after laser skin resurfacing; however, quantitative data are lacking. OBJECTIVE:
      To compare postoperative healing after combination carbon dioxide and erbium:YAG
      full-face laser skin resurfacing in patients who were treated with a silicone
      occlusive dressing (Silon-TSR; Bio Med Sciences, Inc, Bethlehem, Pa) vs open
      wound care consisting of soaks and ointment application. DESIGN: Thirty-five
      patients with closed dressings compared retrospectively with 35 control subjects
      with open-wound care. In a prospective evaluation, 27 patients with closed
      dressings were then compared with 27 historical controls matched by age, sex,
      skin type, and treatment technique. Erythema, crusting, swelling, pain, pruritus,
      purpura, long-term complications, and dressing comfort were evaluated. SETTING:
      Referral-based academic practice. RESULTS: Prospectively, closed-dressing and
      open-wound care groups differed significantly in maximum erythema severity (1.8
      vs 2.0 on a scale of 0-3; P =.03), noticeable erythema duration (15.4 vs 31.1
      days; P =.04), and time until complete erythema resolution (41.8 vs 96.1 days; P
      =.02). Swelling resolution was more rapid in the dressing group (12.1 vs 29.5
      days; P =.02). Crusting was limited to uncovered areas in the dressing group, and
      crusting duration was shorter (5.0 vs 9.1 days; P<.001). Pain was more likely to
      be reported prospectively, but severity was mild, in the closed-dressing group.
      Other short- and long-term complications did not differ significantly. Subjective
      patient attitudes toward the dressing were positive. CONCLUSIONS: Occlusive
      silicone dressing application decreases immediate postoperative morbidity with
      significantly reduced severity and duration of erythema and decreased duration of
      swelling and crusting. Long-term results and complication rates remain unchanged.

PMID- 11594857
TI  - Hyperkeratosis of the nipple and areola: report of 3 cases.
AB  - BACKGROUND: To date, approximately 43 cases of hyperkeratosis of the nipple and
      areola have been reported, most of which have been sporadic. OBSERVATION: We
      describe 3 patients with this dermatosis who were encountered in the outpatient
      clinic of the Department of Dermatology at the American University of Beirut
      Medical Center, Beirut, Lebanon, within a 1-year period. CONCLUSION:
      Hyperkeratosis of the nipple and/or areola may be more common than what has been
      reported in the literature. We propose a revised classification for the
      condition.

PMID- 11594858
TI  - Laser surgical planning with magnetic resonance imaging-based 3-dimensional
      reconstructions for intralesional Nd:YAG laser therapy of a venous malformation
      of the neck.
AB  - BACKGROUND: Three-dimensional (3-D) imaging using computed tomography or magnetic
      resonance imaging data is well known for surgical planning of complex lesions in
      neurosurgery. In dermatology, percutaneous and intralesional Nd:YAG laser therapy
      is well established for numerous types of vascular malformations. Diagnostic
      imaging using ultrasound, computed tomography, or magnetic resonance imaging is
      necessary to plan the laser therapy of those malformations. The therapeutic
      problem is to localize the venous malformation exactly before treatment on
      sectional 2-dimensional images. OBSERVATIONS: We describe a 27-year-old woman
      with a venous malformation of the neck. The data of diagnostic magnetic resonance
      imaging were used for a 3-D reconstruction of the venous malformation to
      demonstrate the anatomical extent and subcutaneous involvement for laser surgical
      planning. Percutaneous and intralesional laser therapy was performed at 3-month
      intervals with the Nd:YAG laser using the 3-D reconstruction as a road map for
      the Nd:YAG laser. Eight weeks after the last laser treatment, the bulky lesions
      of the neck showed regression. Using the 3-D reconstruction for laser surgical
      planning, physicians could perform intralesional laser treatment more exactly.
      The complex anatomy of the venous malformation could be elucidated by studying
      the 3-D images before and during laser surgery. CONCLUSION: The use of magnetic
      resonance imaging-based 3-D reconstructions for laser surgical planning can
      demonstrate the often unexpected extent and improve the intralesional laser
      therapy in the treatment of venous malformations.

PMID- 11594859
TI  - Dermatoscopy turns histopathologist's attention to the suspicious area in
      melanocytic lesions.
AB  - BACKGROUND: Histopathologically, the diagnosis of nevus-associated melanoma or
      melanoma close to a common nevus can be missed if the specimen is cut in a
      nonrepresentative area or if the section shows only the associated common nevus.
      OBJECTIVE: To find out whether dermatoscopy of suspicious areas within a nevus
      can improve the histological diagnosis of malignant melanocytic lesions of the
      skin. MATERIALS: The study was based on dermatoscopic images of more than 2000
      benign and 115 malignant pigmented lesions and a collection of corresponding
      histopathologic slides. METHODS: The dermatoscopic images and the corresponding
      histopathologic diagnoses were compared. In case of differences, the
      histopathologic findings were reevaluated and compared with the dermatoscopic
      findings. RESULTS: Three cases were identified in which melanoma could have been
      histopathologically missed as a result of improper sectioning. After the
      dermatoscopic findings were evaluated, the specimens were reembedded and further
      sections were obtained. Finally, nevus-associated melanoma or melanoma close to a
      common nevus was diagnosed. CONCLUSIONS: Specific dermatoscopic patterns of
      malignancy can be found in highly suspicious areas, eg, broadened networks,
      radial streaming, pseudopods, or dots located at the periphery. The dermatoscopic
      histopathologic correlation can improve the diagnosis of melanoma. Therefore, the
      clinician should point to the most suspicious area with a drawing or image, and
      the suspected diagnosis of melanoma and the history of the lesion should be also
      mentioned.

PMID- 11594860
TI  - Is dermoscopy (epiluminescence microscopy) useful for the diagnosis of melanoma?
      Results of a meta-analysis using techniques adapted to the evaluation of
      diagnostic tests.
AB  - OBJECTIVE: To assess, by means of meta-analysis techniques for diagnostic tests,
      the accuracy of dermoscopic (also known as dermatoscopy and epiluminescence
      microscopy) diagnosis of melanoma performed by experienced observers vs. naked
      eye clinical examination. DATA SOURCES: MEDLINE, EMBASE, PASCAL-BIOMED, and BIUM
      databases were screened through May 31, 2000, without any language restrictions.
      STUDY SELECTION: Original studies were selected when the following criteria were
      met: spectrum of lesions well described, histologic findings as standard
      criterion, and calculated or calculable sensitivity and specificity. Eight of 672
      retrieved references were retained. DATA EXTRACTION: Three investigators
      extracted data. In case of disagreement, consensus was obtained. Summary receiver
      operating characteristic curve analysis was used to describe the central tendency
      of the studies, and to compare dermoscopy and clinical examination. DATA
      SYNTHESIS: Selected studies represented 328 melanomas, mostly less than 0.76 mm
      thick, and 1865 mostly melanocytic benign pigmented skin lesions. For dermoscopic
      diagnosis of melanoma, the sensitivity and specificity ranges were 0.75 to 0.96
      and 0.79 to 0.98, respectively. Dermoscopy had significantly higher
      discriminating power than clinical examination, with respective estimated odds
      ratios of 76 (95% confidence interval, 25-223) and 16 (95% confidence interval, 9
      31) (P =.008), and respective estimated positive likelihood ratios of 9 (95%
      confidence interval, 5.6-19.0) and 3.7 (95% confidence interval, 2.8-5.3). The
      roles of the number of lesions analyzed, the percentage of melanoma lesions, the
      instrument used, and dermoscopic criteria used in each study could not be proved.
      CONCLUSION: For experienced users, dermoscopy is more accurate than clinical
      examination for the diagnosis of melanoma in a pigmented skin lesion.

PMID- 11594861
TI  - Ireland, the Celts, and dermatology.

PMID- 11594862
TI  - Cantharidin revisited: a blistering defense of an ancient medicine.
AB  - Cantharidin, a vesicant produced by beetles in the order Coleoptera, has a long
      history in both folk and traditional medicine. In dermatology, topical
      cantharidin has long been used to treat warts and molluscum. In 1962, cantharidin
      lost Food and Drug Administration (FDA) approval owing to the failure of its
      manufacturers to submit data attesting to cantharidin's efficacy. However, it is
      expected that the FDA will soon include cantharidin on its "Bulk Substances
      List," which would permit physicians or pharmacists to compound cantharidin to be
      used in the office for individual patients. A comprehensive discussion of the
      origins, folk uses, current FDA status, current dermatologic uses, and effects of
      cantharidin poisoning has been compiled herein. No cases of systemic intoxication
      or scarring have been reported with the proper use of cantharidin by a physician.
      Cantharidin is a safe and valuable medication and should be readded to the
      dermatologic therapeutic armamentarium.

PMID- 11594863
TI  - Is dermoscopy useful for the diagnosis of melanoma?

PMID- 11594865
TI  - Recurrent pruritic papules in a 74-year-old man. Diagnosis: lymphomatoid
      papulosis (LyP).

PMID- 11594866
TI  - Axillary mass in a 20-year-old woman. Diagnosis: axillary accessory breast
      tissue.

PMID- 11594867
TI  - Erythematous nodule on a woman's face. Diagnosis: Merkel cell carcinoma.

PMID- 11594868
TI  - A large ulcerated tumor on the back. Diagnosis: solitary giant sebaceous
      carcinoma in a human immunodeficiency virus-positive patient.

PMID- 11594869
TI  - Cytokines may favor a role for human papillomaviruses in the pathogenesis of
      psoriasis.

PMID- 11594870
TI  - The changing face of syphilis: from mimic to disguise.

PMID- 11594871
TI  - Failure of benzathine penicillin in a case of seronegative secondary syphilis in
      a patient with acquired immunodeficiency syndrome: case report and review of the
      literature.

PMID- 11594872
TI  - The handheld dermatoscope improves the recognition of Wickham striae and
      capillaries in Lichen planus lesions.

PMID- 11594873
TI  - The ABCD rule of dermatoscopy does not apply to small melanocytic skin lesions.

PMID- 11594874
TI  - Eosinophilic dermatosis of myeloproliferative disease: characterization of a
      unique eruption in patients with hematologic disorders.

PMID- 11594878
TI  - Relationship between depression and other medical illnesses.

PMID- 11594879
TI  - Home modifications to make older lives easier.

PMID- 11594880
TI  - "Pebbles" cast ripples in health care design.

PMID- 11594881
TI  - New diagnostic criteria for MS issued.

PMID- 11594886
TI  - Academic alert. Insight into opacity: clues to cataract formation.

PMID- 11594887
TI  - Medical vs surgical treatment of gastroesophageal reflux.

PMID- 11594888
TI  - Medical vs surgical treatment of gastroesophageal reflux.

PMID- 11594889
TI  - Medical vs surgical treatment of gastroesophageal reflux.

PMID- 11594890
TI  - Medical vs surgical treatment of gastroesophageal reflux.

PMID- 11594892
TI  - Use of prognostic indexes for determining malpractice liability.

PMID- 11594895
TI  - Sexual transmission during the incubation period of primary HIV infection.

PMID- 11594896
TI  - Integrating primary medical care with addiction treatment: a randomized
      controlled trial.
AB  - CONTEXT: The prevalence of medical disorders is high among substance abuse
      patients, yet medical services are seldom provided in coordination with substance
      abuse treatment. OBJECTIVE: To examine differences in treatment outcomes and
      costs between integrated and independent models of medical and substance abuse
      care as well as the effect of integrated care in a subgroup of patients with
      substance abuse-related medical conditions (SAMCs). DESIGN: Randomized controlled
      trial conducted between April 1997 and December 1998. SETTING AND PATIENTS: Adult
      men and women (n = 592) who were admitted to a large health maintenance
      organization chemical dependency program in Sacramento, Calif. INTERVENTIONS:
      Patients were randomly assigned to receive treatment through an integrated model,
      in which primary health care was included within the addiction treatment program
      (n = 285), or an independent treatment-as-usual model, in which primary care and
      substance abuse treatment were provided separately (n = 307). Both programs were
      group based and lasted 8 weeks, with 10 months of aftercare available. MAIN
      OUTCOME MEASURES: Abstinence outcomes, treatment utilization, and costs 6 months
      after randomization. RESULTS: Both groups showed improvement on all drug and
      alcohol measures. Overall, there were no differences in total abstinence rates
      between the integrated care and independent care groups (68% vs 63%, P =.18). For
      patients without SAMCs, there were also no differences in abstinence rates
      (integrated care, 66% vs independent care, 73%; P =.23) and there was a slight
      but nonsignificant trend of higher costs for the integrated care group ($367.96
      vs $324.09, P =.19). However, patients with SAMCs (n = 341) were more likely to
      be abstinent in the integrated care group than the independent care group (69% vs
      55%, P =.006; odds ratio [OR], 1.90; 95% confidence interval [CI], 1.22-2.97).
      This was true for both those with medical (OR, 3.38; 95% CI, 1.68-6.80) and
      psychiatric (OR, 2.10; 95% CI, 1.04-4.25) SAMCs. Patients with SAMCs had a slight
      but nonsignificant trend of higher costs in the integrated care group ($470.81 vs
      $427.95, P =.14). The incremental cost-effectiveness ratio per additional
      abstinent patient with an SAMC in the integrated care group was $1581.
      CONCLUSIONS: Individuals with SAMCs benefit from integrated medical and substance
      abuse treatment, and such an approach can be cost-effective. These findings are
      relevant given the high prevalence and cost of medical conditions among substance
      abuse patients, new developments in medications for addiction, and recent
      legislation on parity of substance abuse with other medical benefits.

PMID- 11594897
TI  - Methadone maintenance in primary care: a randomized controlled trial.
AB  - CONTEXT: Methadone maintenance is an effective treatment for opioid dependence,
      yet its use is restricted to federally licensed narcotic treatment programs
      (NTPs). Office-based care of stabilized methadone maintenance patients is a
      promising alternative but no data are available from controlled trials regarding
      this type of program. OBJECTIVE: To determine the feasibility and efficacy of
      office-based methadone maintenance by primary care physicians vs in an NTP for
      stable opioid-dependent patients. DESIGN: Six-month, randomized controlled open
      clinical trial conducted February 1999-March 2000. SETTING: Offices of 6 primary
      care internists and an NTP. PATIENTS: Forty-seven opioid-dependent patients who
      had been receiving methadone maintenance therapy in an NTP without evidence of
      illicit drug use for 1 year and without significant untreated psychiatric
      comorbidity were randomized; 1 patient refused to participate after treatment
      assignment to NTP. INTERVENTIONS: Patients were randomly assigned to receive
      office-based methadone maintenance from primary care physicians, who received
      specialized training in the care of opioid-dependent patients (n = 22), or usual
      care at an NTP (n = 24). MAIN OUTCOME MEASURES: Illicit drug use, clinical
      instability (persistent drug use), patient and clinician satisfaction, functional
      status, and use of health, legal, and social services, compared between the 2
      groups. RESULTS: Eleven of 22 (50%; 95% confidence interval [CI], 29%-71%)
      patients in office-based care compared with 9 of 24 (38%; 95% CI, 21%-57%) of NTP
      patients had a self-report or urine toxicology test result indicating illicit
      opiate use (P =.39). Hair toxicology testing detected an additional 2 patients in
      each treatment group with evidence of illicit drug use, but this did not change
      the overall findings. Ongoing illicit drug use meeting criteria for clinical
      instability occurred in 4 of 22 (18%; 95% CI, 7%-39%) patients in office-based
      care compared with 5 of 24 (21%; 95% CI, 9%-41%) NTP patients (P =.82). Sixteen
      of the 22 (73%; 95% CI, 54%-92%) office-based patients compared with 3 of the 24
      (13%; 95% CI, 0%-26%) NTP patients thought the quality of care was excellent (P
      =.001). There were no differences over time within or between groups in
      functional status or use of health, legal, or social services. CONCLUSIONS: Our
      results support the feasibility and efficacy of transferring stable opioid
      dependent patients receiving methadone maintenance to primary care physicians'
      offices for continuing treatment and suggest guidelines for identifying patients
      and clinical monitoring.

PMID- 11594898
TI  - Supplemental insurance and use of effective cardiovascular drugs among elderly
      medicare beneficiaries with coronary heart disease.
AB  - CONTEXT: Cost-sharing in US prescription drug coverage plans for elderly persons
      varies widely. Evaluation of prescription drug use among elderly persons by type
      of health insurance could provide useful information for designing a Medicare
      drug program. OBJECTIVE: To determine use of effective cardiovascular drugs among
      elderly persons with coronary heart disease (CHD) by type of health insurance.
      DESIGN, SETTING, AND PATIENTS: Cross-sectional evaluation of 1908 community
      dwelling adults, aged 66 years or older, with a history of CHD or myocardial
      infarction from the 1997 Medicare Current Beneficiary Survey, a nationally
      representative sample of Medicare beneficiaries. MAIN OUTCOME MEASURES: Use of 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), beta
      blockers, and nitrates, and out-of-pocket expenditures for prescription drugs,
      stratified by type of health insurance: Medicare without drug coverage (Medicare
      only or self-purchased supplemental insurance) or with drug coverage (Medicaid,
      other public program, Medigap, health maintenance organization, or employer
      sponsored plan). RESULTS: Statin use ranged from 4.1% in Medicare patients with
      no drug coverage to 27.4% in patients with employer-sponsored drug coverage
      (P<.001). Less variation between these 2 types occurred for beta-blockers (20.7%
      vs 36.1%; P =.003) and nitrates (20.4% vs 38.0%; P =.005). In multivariate
      analyses, statin use remained significantly lower for patients with Medicare only
      (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.05-0.49) and beta-blocker
      use was lower for Medicaid patients (OR, 0.55; 95% CI, 0.34-0.88) vs those with
      employer-sponsored coverage. Nitrate use occurred less frequently in persons
      lacking drug coverage (patients with Medicare only, P =.049; patients with
      supplemental insurance without drug coverage, P =.03). Patients with Medicare
      only spent a much larger fraction of income on prescription drugs compared with
      those with employer-sponsored drug coverage (7.9% vs 1.7%; adjusted P<.001).
      CONCLUSION: Elderly Medicare beneficiaries with CHD who lack drug coverage have
      disproportionately large drug expenditures and lower use rates of statins, a
      class of relatively expensive drugs that improve survival.

PMID- 11594899
TI  - Comparison of a whole-blood interferon gamma assay with tuberculin skin testing
      for detecting latent Mycobacterium tuberculosis infection.
AB  - CONTEXT: Identifying persons with latent tuberculosis infection (LTBI) is crucial
      to the goal of TB elimination. A whole-blood interferon gamma (IFN-gamma) assay,
      the QuantiFERON-TB test, is a promising in vitro diagnostic test for LTBI that
      has potential advantages over the tuberculin skin test (TST). OBJECTIVES: To
      compare the IFN-gamma assay with the TST and to identify factors associated with
      discordance between the tests. DESIGN AND SETTING: Prospective comparison study
      conducted at 5 university-affiliated sites in the United States between March 1,
      1998 and June 30, 1999. PARTICIPANTS: A total of 1226 adults (mean age, 39 years)
      with varying risks of Mycobacterium tuberculosis infection or documented or
      suspected active TB, all of whom underwent both the IFN-gamma assay and the TST.
      MAIN OUTCOME MEASURE: Level of agreement between the IFN-gamma assay and the TST.
      RESULTS: Three hundred ninety participants (31.8%) had a positive TST result and
      349 (28.5%) had a positive IFN-gamma assay result. Overall agreement between the
      IFN-gamma assay and the TST was 83.1% (kappa = 0.60). Multivariate analysis
      revealed that the odds of having a positive TST result but negative IFN-gamma
      assay result were 7 times higher for BCG-vaccinated persons compared with
      unvaccinated persons. The IFN-gamma assay provided evidence that among
      unvaccinated persons with a positive TST result but negative IFN-gamma assay
      result, 21.2% were responding to mycobacteria other than M tuberculosis.
      CONCLUSIONS: For all study participants, as well as for those being screened for
      LTBI, the IFN-gamma assay was comparable with the TST in its ability to detect
      LTBI, was less affected by BCG vaccination, discriminated responses due to
      nontuberculous mycobacteria, and avoided variability and subjectivity associated
      with placing and reading the TST.

PMID- 11594900
TI  - Has misdiagnosis of appendicitis decreased over time? A population-based
      analysis.
AB  - CONTEXT: Misdiagnosis of presumed appendicitis is an adverse outcome that leads
      to unnecessary surgery. Computed tomography, ultrasonography, and laparoscopy
      have been suggested for use in patients with equivocal signs of appendicitis to
      decrease unnecessary surgery. OBJECTIVE: To determine if frequency of
      misdiagnosis preceding appendectomy has decreased with increased availability of
      computed tomography, ultrasonography, and laparoscopy. DESIGN, SETTING, AND
      PATIENTS: Retrospective, population-based cohort study of data from a Washington
      State hospital discharge database for 85 790 residents assigned International
      Classification of Diseases, Ninth Revision procedure codes for appendectomy, and
      United States Census Bureau data for 1987-1998. MAIN OUTCOME MEASURE: Population
      based age- and sex-standardized incidence of appendectomy with acute appendicitis
      (perforated or not) or with a normal appendix. RESULTS: Among 63 707
      nonincidental appendectomy patients, 84.5% had appendicitis (25.8% with
      perforation) and 15.5% had no associated diagnosis of appendicitis. After
      adjusting for age and sex, the population-based incidence of unnecessary
      appendectomy and of appendicitis with perforation did not change significantly
      over time. Among women of reproductive age, the population-based incidence of
      misdiagnosis increased 1% per year (P =.005). The incidence of misdiagnosis
      increased 8% yearly in patients older than 65 years (P<.001) but did not change
      significantly in children younger than 5 years (P =.17). The proportion of
      patients undergoing laparoscopic appendectomy who were misdiagnosed was
      significantly higher than that of open appendectomy patients (19.6% vs 15.5%;
      P<.001). CONCLUSION: Contrary to expectation, the frequency of misdiagnosis
      leading to unnecessary appendectomy has not changed with the introduction of
      computed tomography, ultrasonography, and laparoscopy, nor has the frequency of
      perforation decreased. These data suggest that on a population level, diagnosis
      of appendicitis has not improved with the availability of advanced diagnostic
      testing.

PMID- 11594901
TI  - Serial evaluation of the SOFA score to predict outcome in critically ill
      patients.
AB  - CONTEXT: Evaluation of trends in organ dysfunction in critically ill patients may
      help predict outcome. OBJECTIVE: To determine the usefulness of repeated
      measurement the Sequential Organ Failure Assessment (SOFA) score for prediction
      of mortality in intensive care unit (ICU) patients. DESIGN: Prospective,
      observational cohort study conducted from April 1 to July 31, 1999. SETTING: A 31
      bed medicosurgical ICU at a university hospital in Belgium. PATIENTS: Three
      hundred fifty-two consecutive patients (mean age, 59 years) admitted to the ICU
      for more than 24 hours for whom the SOFA score was calculated on admission and
      every 48 hours until discharge. MAIN OUTCOME MEASURES: Initial SOFA score (0-24),
      Delta-SOFA scores (differences between subsequent scores), and the highest and
      mean SOFA scores obtained during the ICU stay and their correlations with
      mortality. RESULTS: The initial, highest, and mean SOFA scores correlated well
      with mortality. Initial and highest scores of more than 11 or mean scores of more
      than 5 corresponded to mortality of more than 80%. The predictive value of the
      mean score was independent of the length of ICU stay. In univariate analysis,
      mean and highest SOFA scores had the strongest correlation with mortality,
      followed by Delta-SOFA and initial SOFA scores. The area under the receiver
      operating characteristic curve was largest for highest scores (0.90; SE, 0.02;
      P<.001 vs initial score). When analyzing trends in the SOFA score during the
      first 96 hours, regardless of the initial score, the mortality rate was at least
      50% when the score increased, 27% to 35% when it remained unchanged, and less
      than 27% when it decreased. Differences in mortality were better predicted in the
      first 48 hours than in the subsequent 48 hours. There was no significant
      difference in the length of stay among these groups. Except for initial scores of
      more than 11 (mortality rate >90%), a decreasing score during the first 48 hours
      was associated with a mortality rate of less than 6%, while an unchanged or
      increasing score was associated with a mortality rate of 37% when the initial
      score was 2 to 7 and 60% when the initial score was 8 to 11. CONCLUSIONS:
      Sequential assessment of organ dysfunction during the first few days of ICU
      admission is a good indicator of prognosis. Both the mean and highest SOFA scores
      are particularly useful predictors of outcome. Independent of the initial score,
      an increase in SOFA score during the first 48 hours in the ICU predicts a
      mortality rate of at least 50%.

PMID- 11594902
TI  - Natural limits of pregnancy testing in relation to the expected menstrual period.
AB  - CONTEXT: Pregnancy test kits routinely recommend testing "as early as the first
      day of the missed period." However, a pregnancy cannot be detected before the
      blastocyst implants. Due to natural variability in the timing of ovulation,
      implantation does not necessarily occur before the expected onset of next menses.
      OBJECTIVE: To estimate the maximum screening sensitivity of pregnancy tests when
      used on the first day of the expected period, taking into account the natural
      variability of ovulation and implantation. DESIGN AND SETTING: Community-based
      prospective cohort study conducted in North Carolina between 1982 and 1986.
      PARTICIPANTS: Two hundred twenty-one healthy women 21 to 42 years of age who were
      planning to conceive. MAIN OUTCOME MEASURES: Day of implantation, defined by the
      serial assay of first morning urine samples using an extremely sensitive
      immunoradiometric assay for human chorionic gonadotropin (hCG), relative to the
      first day of the missed period, defined as the day on which women expected their
      next menses to begin, based on self-reported usual cycle length. RESULTS: Data
      were available for 136 clinical pregnancies conceived during the study, 14 (10%)
      of which had not yet implanted by the first day of the missed period. The highest
      possible screening sensitivity for an hCG-based pregnancy test therefore is
      estimated to be 90% (95% confidence interval [CI], 84%-94%) on the first day of
      the missed period. By 1 week after the first day of the missed period, the
      highest possible screening sensitivity is estimated to be 97% (95% CI, 94%-99%).
      CONCLUSIONS: In this study, using an extremely sensitive assay for hCG, 10% of
      clinical pregnancies were undetectable on the first day of missed menses. In
      practice, an even larger percentage of clinical pregnancies may be undetected by
      current test kits on this day, given their reported assay properties and other
      practical limitations.

PMID- 11594903
TI  - Affordable prescriptions for the elderly.

PMID- 11594904
TI  - Generalist physicians and addiction care: from turfing to sharing the turf.

PMID- 11594909
TI  - Potential utility of diffusion-weighted imaging in venous infarction.

PMID- 11594910
TI  - The early identification of candidates for epilepsy surgery.
AB  - The effectiveness of resective surgery for the treatment of carefully selected
      patients with medically intractable, localization-related epilepsy is clear.
      Seizure-free rates following temporal lobectomy are consistently 65% to 70% in
      adults and 68% to 78% in children. Extratemporal resections less commonly lead to
      a seizure-free outcome, although one recent childhood series reported a seizure
      free rate of 62% following extratemporal epilepsy surgery. With both temporal and
      extratemporal resections, additional patients have a reduction in seizures
      following surgery but are not completely seizure free. The identification of
      favorable surgical candidates has been the subject of extensive research, and
      many investigators have examined predictors of outcome following epilepsy
      surgery. However, the early identification of the potential epilepsy surgery
      candidate and the optimal timing of surgery have only occasionally been addressed
      in the literature. This issue is methodologically challenging to study since
      studies require large numbers of patients with new-onset partial epilepsy who are
      followed over time. The purpose of this article is to review the current ability
      for early prediction of medical intractability in patients with surgically
      remediable epilepsy. Emphasis will be placed on the early prediction of
      intractable temporal lobe epilepsy in children and adolescents, since temporal
      lobectomy remains the prototype epilepsy surgery, and early surgery may improve
      psychosocial outcome in younger patients.

PMID- 11594911
TI  - Neuropathic central pain: epidemiology, etiology, and treatment options.
AB  - BACKGROUND: Nociceptive pain is a major problem in clinical neurology. Peripheral
      nerve injury may change the physiology of the dorsal horn so that pain becomes
      progressively centralized. OBJECTIVE: To review mechanisms underlying the
      plasticity of dorsal root ganglia and dorsal horn neurons that lead to central
      pain from a peripheral nerve injury. RESULTS: Evidence is reviewed that points to
      molecular changes in nociceptive terminals, ectopic firing of afferent pain
      fibers at the level of the dorsal root ganglia, and physiologic changes of the N
      methyl-D-aspartate receptor that cause chronic nociceptive pain. CONCLUSIONS:
      Central sensitization is the physiologic manifestation of many severe
      peripherally induced pain states. It is maintained by nociceptive input and a
      physiologic change in the N-methyl-D-aspartate receptor. It consists of: (1)
      hypersensitivity at the site of injury; (2) mechanoallodynia; (3) thermal
      hyperalgesia; (4) hyperpathia; (5) extraterritoriality in the case of complex
      regional pain syndrome/reflex sympathetic dystrophy; and (6) associated
      neurogenic inflammation, autonomic dysregulation, and motor phenomena.

PMID- 11594912
TI  - Neuroprotection and traumatic brain injury: the search continues.

PMID- 11594913
TI  - Human immunodeficiency virus and the peripheral nervous system workshop.
AB  - To provide a venue for a comprehensive multidisciplinary review of the current
      state of knowledge regarding the human immunodeficiency virus-associated
      peripheral neuropathies and to provide the institute with guidance in formulating
      future research initiatives, the National Institute of Neurological Disorders and
      Stroke (Bethesda, Md) convened a workshop on September 18 through 19, 2000. The
      participants were chosen from various disciplines and included clinicians,
      pathologists, neurobiologists, neurophysiologists, virologists, and
      neuroimmunologists. The present article summarizes the highlights of the meeting
      and includes the recommendations developed by the participants for future
      research. As might be expected in a rapidly evolving scientific field, the
      meeting was characterized by a lively and far-ranging discussion of data
      interpretation, experimental approaches, and priorities for future research.
      However, the recommendations presented at the end of this article constitute a
      consensus judgment reached by all of the participants of the most important areas
      for future research.

PMID- 11594914
TI  - Diffusion-weighted magnetic resonance in cerebral venous thrombosis.
AB  - BACKGROUND: Cerebral venous thrombosis (CVT) is a cause of stroke with obscure
      pathophysiologic properties that differ from arterial stroke. Its main mechanisms
      of pathophysiology are the breakdown of the blood-brain barrier and the
      coexistence of cytotoxic and vasogenic edema. However, conventional magnetic
      resonance imaging (MRI) cannot differentiate between vasogenic and cytotoxic
      edema. OBJECTIVES: To describe the diffusion-weighted imaging (DWI) findings and
      characterize the clinical applications of DWI in CVT. SETTING: A tertiary
      referral center, neurology department. DESIGN AND METHODS: From November 1998 to
      March 2001, 14 patients (5 men, 9 women; mean age, 43 +/- 10 years) with CVT
      underwent DWI, conventional MRI, MR venography, or conventional cerebral
      angiography. Abnormal findings on DWI and conventional MRI indicated the
      necessity of MR venography and conventional angiography to confirm the diagnosis
      of CVT. Apparent diffusion coefficient (ADC) values were measured in all of the
      abnormal lesions with visual inspection of DWI and T2-weighted echo planar
      imaging. RESULTS: Findings on DWI were grouped according to 3 patterns: (1)
      Heterogeneous signal intensity (SI) (10 patients) showed mixed bright high SI and
      low SI and the corresponding ADC values were inversely correlated to the DWI SI.
      The areas of prominent low SI on DWI were reversed with adequate treatment on
      follow-up MRI in 1 patient. (2) Multifocal high SI (3 patients) was similar to
      that observed in acute arterial stroke. The corresponding ADC values were
      decreased and DWI was performed in the acute stages. (3) Intravascular clot with
      high SI was found with (1 patient, also in heterogeneous SI group) or without (1
      patient) parenchymal lesions. In 1 patient, DWI demonstrated T2-negative and
      fluid attenuated inversion recovery-negative lesions without correlative
      symptoms. CONCLUSIONS: These data suggest that DWI with ADC maps can be used to
      discriminate between types of edema for tissue viability and to provide
      information about stages and diagnostic clues in CVT.

PMID- 11594915
TI  - Increase in peripheral CD4 bright+ CD8 dull+ T cells in Parkinson disease.
AB  - BACKGROUND: Immune abnormalities are known to be involved in the pathogenesis of
      sporadic Parkinson disease. OBJECTIVE: To examine whether abnormalities in
      peripheral lymphocytes exist in Parkinson disease. METHODS: Immune mediators,
      including CD1a, CD3, CD4, CD8, CD45RO, and Fas (CD95), were examined in
      peripheral lymphocytes of patients by 3-color flow cytometry. RESULTS: Patients
      with Parkinson disease displayed a significantly greater population of
      circulating CD3+ CD4 bright+ CD8 dull+ lymphocytes than age-matched control
      subjects (P =.005) and patients with cerebrovascular disease (P =.002). The
      increase in these cells appeared to continue for at least 17 months. These T
      cells also expressed CD45RO and Fas, markers for activated T cells, while CD1a, a
      marker for thymic T cells, was negative, suggesting that these cells are mature T
      cells with immune activities. CONCLUSIONS: As CD4+ CD8+ T cells are known to
      increase after some specific viral infections, the continuous increase in CD4
      bright+ CD8 dull+ T cells shown here may indicate postinfectious immune
      abnormalities that are possibly associated with the pathogenesis of this slowly
      progressive, multifactorial neurodegenerative disease.

PMID- 11594916
TI  - Mild tremor in relatives of patients with essential tremor: what does this tell
      us about the penetrance of the disease?
AB  - BACKGROUND: Mild tremor may occur in relatives of patients with essential tremor
      (ET). However, this phenomenon has not been studied quantitatively or with a
      comparison group. Such a study may provide information on the penetrance of ET.
      OBJECTIVE: To obtain data on the magnitude of tremor in case and control
      relatives who did not meet diagnostic criteria for ET. METHODS: Cases with ET and
      control subjects from the Washington Heights-Inwood community in northern
      Manhattan, NY, were enrolled in a family study. Their first- and second-degree
      relatives underwent a videotaped tremor examination. Two neurologists rated the
      severity of tremor, assigning a total tremor score (0-36 [maximum]). Data were
      analyzed on 201 case relatives and 212 control relatives who did not meet
      diagnostic criteria for ET. RESULTS: The mean total tremor score of first-degree
      case relatives was higher than that of first-degree control relatives (4.9 vs
      3.9; P<.003). Total tremor scores for second-degree relatives did not differ (4.1
      vs 4.2; P =.68). A larger percentage (55.2% vs 36.6%; P =.01) of first-degree
      case relatives had total tremor scores of 4 or more. Among first-degree relatives
      who were older than 60 years, 13 case relatives (59.1%) and 18 control relatives
      (45.0%) had total tremor scores of 4 or more. CONCLUSIONS: A considerable number
      of seemingly normal case relatives may have a genetic predisposition for tremor.
      Even among older case relatives (> or =60 years of age), there was an increased
      prevalence of higher tremor scores, suggesting that in that age group,
      subclinical ET may be present and penetrance still may not be complete.

PMID- 11594917
TI  - Hippocampal atrophy correlates with clinical features of Alzheimer disease in
      African Americans.
AB  - CONTEXT: Imaging measurements may aid in the characterization and diagnosis of
      patients with Alzheimer disease (AD). Most research studies, however, have been
      performed on predominantly white study groups despite the fact that there may be
      biological differences in AD between African American and white patients.
      OBJECTIVE: To measure hippocampal volume in African American patients with AD and
      to correlate these measurements with the presence of AD and neuropsychological
      test performance. DESIGN: Survey study. SETTING: Academic center. PARTICIPANTS:
      Fifty-four healthy African American subjects and 32 African American patients
      with AD were studied. Hippocampal volumes were measured in all subjects from
      magnetic resonance images using established methods. MAIN OUTCOME MEASURE:
      Correlations were assessed between hippocampal volume and demographic variables,
      clinical group membership, and neuropsychological performance. RESULTS: The
      hippocampi of patients were atrophic with respect to those of healthy subjects
      (P<.01). Significant direct correlations were present between hippocampal volumes
      and performance on several different neuropsychological tests (r>0.5 and P<.01
      for every test evaluated) when patients and healthy subjects were combined.
      CONCLUSIONS: Hippocampal atrophy is a feature of AD in African Americans as it is
      in white subjects. The neuropsychological-hippocampal volume correlations
      indicate that hippocampal volume measurements do represent a measure of the
      structural substrate of functional impairment in AD.

PMID- 11594918
TI  - Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10
      years.
AB  - OBJECTIVE: To reassess, in a cohort of patients with early-onset multiple
      sclerosis, the long-term evolution of cognitive deficits, their relationship to
      the disease's clinical progression, and their effects on daily life. DESIGN: Ten
      years after our baseline assessment, we again compared the cognitive performance
      of patients and control subjects on a neuropsychological test battery. Clinical
      and demographic correlates of cognitive impairment and their effects on everyday
      functioning were determined by multiple linear regression analysis. SETTING: The
      research clinic of a university department of neurology. PARTICIPANTS: Forty-five
      inpatients and outpatients with multiple sclerosis and 65 demographically matched
      healthy controls from the original sample. MAIN OUTCOME MEASURES: Mean scores of
      both groups on the neuropsychological test battery in initial and 2 follow-up
      evaluations (about 4 and 10 years, respectively); number of cognitively impaired
      subjects, defined by the number of subtests failed; regression coefficients
      measuring the relationship between clinical variables and cognitive outcome and
      between mental decline and everyday functioning assessed by the Environmental and
      the Incapacity Status Scales. RESULTS: Previously detected cognitive defects in
      verbal memory, abstract reasoning, and linguistic processes were confirmed on the
      third testing, at which time deficits in attention/short-term spatial memory also
      emerged. Only 20 of 37 patients who were cognitively unimpaired on initial
      testing remained so by the end of the follow-up, when the proportion of subjects
      who were cognitively impaired reached 56%. Degree of physical disability,
      progressive disease course, and increasing age predicted the extent of cognitive
      decline. Disability level and degree of cognitive impairment were independent
      predictors of a patient's handicap in the workplace and in social settings.
      CONCLUSIONS: In the course of a sufficiently long follow-up, cognitive
      dysfunction is likely to emerge and progress in a sizable proportion of patients.
      As multiple sclerosis advances, neurological and cognitive involvement tend to
      converge. Limitations in a patient's work and social activities are correlated
      with the extent of cognitive decline, independent of degree of physical
      disability.

PMID- 11594919
TI  - Functional decline in Parkinson disease.
AB  - OBJECTIVES: To determine the overall rate of functional decline and to assess the
      progression of different signs of Parkinson disease (PD). PATIENTS AND METHODS:
      Patients with clinically diagnosed PD followed up for at least 3 years were
      included in this study. Demographic and clinical data (including the Unified
      Parkinson's Disease Rating Scale [UPDRS]) were analyzed by the multivariate
      unbalanced repeated-measurements design using the mixed-effects model to study
      the association between different symptoms and various demographic variables.
      Regression models helped estimate the rates of progression of the disease in
      relationship to the various components of the UPDRS. Patients were categorized as
      having tremor-dominant or postural instability-gait difficulty-dominant PD and
      the 2 categories were compared for progression of their total UPDRS scores.
      DESIGN: A multivariate mixed-effects model was used to study the relationship
      between the different symptoms and various demographic variables. Nonparametric
      statistical tests were used to compare the progression of symptoms in the "on"
      (good function) state and the "off" (poor function) state groups for 2 age-at
      onset categories (< or =57 and >57 years). RESULTS: Data from 1731 visits on 297
      patients (181 men) followed up for an average of 6.36 years (range, 3-17 years)
      were analyzed. The annual rate of decline in the total UPDRS scores was 1.34 when
      assessed during the on state and 1.58 when assessed during the off state.
      Patients with an older age at onset had more rapid progression of PD than those
      with a younger age at onset. Furthermore, the older-onset group had statistically
      significantly more progression in mentation, freezing, and parts I (mentation)
      and II (activities of daily living) UPDRS subscores. Handwriting was the only
      component of the UPDRS score that did not notably deteriorate during the
      observation period. Regression analysis of 108 patients whose symptoms were rated
      during their off state showed a faster rate of cognitive decline as age at onset
      increased. The slopes (ie, the annual rates of decline) of progression in the
      UPDRS scores, when adjusted for age at the initial visit, were steeper for the
      postural instability--gait difficulty--dominant group compared with the tremor
      dominant group. CONCLUSION: Based on longitudinal follow-up data, our findings
      provide evidence for a variable course of progression of the different PD
      symptoms, thus implying different biochemical or degenerative mechanisms for the
      various clinical features associated with PD.

PMID- 11594920
TI  - The coagulation-fibrinolysis system in patients with leukoaraiosis and Binswanger
      disease.
AB  - BACKGROUND: Hypercoagulability is observed in vascular dementia, including
      Binswanger disease. However, the correlation between hypercoagulability,
      leukoaraiosis, and dementia remains unclear. OBJECTIVE: To examine how activation
      of the coagulation fibrinolysis correlates with leukoaraiosis and dementia.
      PATIENTS AND METHODS: Thrombin-antithrombin complex (TAT), prothrombin fragment(1
      + 2) (F1 + 2) and cross-linked D-dimer (XDP) were measured consecutively in 18
      subjects without dementia and with leukoaraiosis, and in 29 subjects with
      subcortical vascular dementia and severe leukoaraiosis (Binswanger disease) at
      either stable or deteriorating stages. They were compared with 19 patients with
      old lacunar infarctions and 24 patients with other neurological diseases. We also
      examined the indices of cognitive impairment and brain atrophy. In each group,
      the ventricular area-cranial space area ratio was measured by an image analyzer.
      RESULTS: Patients with Binswanger disease who were exclusively at deteriorating
      stages showed increased TAT and XDP levels and an increased ventricular area
      cranial space area ratio, as compared with the patients with other neurological
      diseases (P<.001). The index of cognitive impairment in patients at a
      deteriorating stage showed a decreasing trend vs that of patients in the stable
      stage. Among the variables that were significantly associated with a
      hypercoagulable condition (ie, age, scores on Mini-Mental State Examination or
      the Hasegawa Dementia Rating Scale, Revised [MMSE/HDRS], white matter lesions,
      ventricular area-cranial space area ratio, and C-reactive protein), age (odds
      ratio [OR], 2.82) and MMSE/HDSR scores (OR, 0.43) survived as predictors for
      coagulation activation, and C-reactive protein survived for fibrinolysis
      activation (OR, 4.63) in multivariate analysis. CONCLUSION: Hypercoagulability in
      a subgroup of patients with Binswanger disease and with more severe cognitive
      impairment and brain atrophy does not support a triggering role for a coagulation
      fibrinolysis system, although it may contribute to worsening of neurological
      deficits.

PMID- 11594921
TI  - Clinical correlates of action tremor in Parkinson disease.
AB  - BACKGROUND: Action tremor is often noted in patients with Parkinson disease (PD),
      yet the clinical correlates of this type of tremor have been the focus of few
      studies. It is not clear whether this action tremor is a manifestation of the
      underlying basal ganglia disease. OBJECTIVE: To determine whether the severity of
      action tremor in PD is associated with age, age at disease onset, disease
      duration, levodopa dose, severity of rest tremor, or other motor (ie,
      bradykinesia, rigidity) and nonmotor manifestations of PD. METHODS: Patients with
      PD (N = 197) were ascertained as part of a familial aggregation study. All
      patients underwent a neurological examination. Rest tremor was rated with the
      Unified Parkinson Disease Rating Scale; and action tremor, with the Washington
      Heights-Inwood Genetic Study of Essential Tremor Rating Scale. RESULTS: Action
      tremor was present in 184 (93.4%) of 197 patients. Four patients (2%) met
      criteria for definite essential tremor. The action tremor score was not
      associated with age, age at onset, or disease duration. The action tremor score
      was associated with the rest tremor score (r = 0.37; P<.001), and more strongly
      with the ipsilateral than contralateral rest tremor score. The association
      between the action tremor score and the rest tremor score was diminished but
      still significant (r = 0.21, P<.02) even when we excluded these 63 patients with
      re-emergent tremor. Neither the action nor the rest tremor score was associated
      with the bradykinesia or rigidity scores, Hoehn and Yahr scale score, or modified
      Mini-Mental State Examination score. CONCLUSIONS: Action tremor was associated
      with rest tremor in PD, suggesting that, at least in part, action tremor is a
      manifestation of the underlying basal ganglia disease. Neither tremor was
      associated with other motor and nonmotor manifestations of PD. This in turn
      suggests that tremor in PD may represent an underlying pathophysiological process
      different from these other manifestations.

PMID- 11594922
TI  - Hereditary neuropathy with liability to pressure palsies is not a major cause of
      idiopathic carpal tunnel syndrome.
AB  - BACKGROUND: Carpal tunnel syndrome is a debilitating neuropathy affecting
      millions of individuals. Although there are published reports of familial
      associations of carpal tunnel syndrome, the molecular mechanisms are unknown.
      OBJECTIVE: To determine the prevalence and potential role of the chromosome 17
      microdeletion associated with hereditary neuropathy with liability to pressure
      palsies in patients diagnosed as having carpal tunnel syndrome. DESIGN:
      Prospective study. PATIENTS AND METHODS: Since hereditary neuropathy with
      liability to pressure palsies may present as carpal tunnel syndrome, we evaluated
      50 patients with idiopathic carpal tunnel syndrome for hereditary neuropathy with
      liability to pressure palsies. RESULTS: No hereditary neuropathy with liability
      to pressure palsies deletions were detected. CONCLUSION: Molecular genetic
      testing for hereditary neuropathy with liability to pressure palsies in patients
      with idiopathic carpal tunnel syndrome is of limited value.

PMID- 11594923
TI  - Association of incident Alzheimer disease and blood pressure measured from 13
      years before to 2 years after diagnosis in a large community study.
AB  - BACKGROUND: It is uncertain whether high blood pressure increases the risk of
      developing Alzheimer disease (AD). OBJECTIVE: To examine the association between
      incident AD and blood pressure measured up to 13 years before diagnosis. DESIGN:
      Longitudinal cohort study conducted from 1982 to 1988, with blood pressure
      measured every 3 years in home interviews, and in 1973 for a portion (60%) of the
      sample. SETTING: Community of East Boston, Mass. PARTICIPANTS: Six hundred thirty
      four subjects 65 years or older and without AD were selected as a stratified
      random sample of participants of the East Boston Established Populations for
      Epidemiologic Studies of the Elderly. MAIN OUTCOME MEASURE: Alzheimer disease was
      diagnosed by a neurologist using a structured clinical evaluation. RESULTS: High
      blood pressure was not associated with an increased risk of AD in logistic
      regression models adjusted for age, sex, and level of education. There was no
      association with systolic pressure measured 13 years before diagnosis (odds ratio
      = 1.03/10 mm Hg; 95% confidence interval, 0.80-1.32) and an inverse association
      with systolic pressure measured 4 years before diagnosis (odds ratio = 0.82/10 mm
      Hg; 95% confidence interval, 0.72-0.95). Associations for diastolic pressure were
      in the same direction as those for systolic pressure except with wider confidence
      intervals. The odds ratios were not materially different with further adjustment
      for cardiovascular risk factors and diseases. CONCLUSION: In this large community
      study, high blood pressure was not associated with an increased risk of AD.

PMID- 11594924
TI  - Association of moderate polyglutamine tract expansions in the slow calcium
      activated potassium channel type 3 with ataxia.
AB  - BACKGROUND: The small-conductance calcium-activated potassium channel gene
      (hSKCa3) contains 2 CAG repeats, 1 of which is highly polymorphic. Although this
      repeat is not pathologically expanded in patients with schizophrenia, some
      studies have suggested an allelic association with schizophrenia. CAG expansions
      in other genes such as the alpha1 subunit of a brain-specific P/Q-type calcium
      channel gene cause spinocerebellar ataxia type 6, whereas the length of the CAG
      repeat in the RAI1 gene modifies the age of onset of spinocerebellar ataxia type
      2. OBJECTIVES: To evaluate expansions in the hSKCa3 polyglutamine domain as
      causative for ataxia, and to study the association between the length of the
      polyglutamine repeat and the presence of ataxia. METHODS: We analyzed this repeat
      in 122 patients with autosomal dominant cerebellar ataxia, or sporadic ataxia,
      and compared allele distribution with 750 alleles seen in 2 healthy control
      groups and 172 alleles in patients with Parkinson disease. RESULTS: The
      distribution of alleles in ataxia patients and controls was significantly
      different by Wilcoxon rank test (P <.001). Twenty-two or more polyglutamine
      tracts were more common in ataxia patients compared with controls by chi2
      analysis (P<.001). CONCLUSION: Longer stretches of polyglutamines in a human
      potassium channel are not causative for ataxia, but they are associated with the
      presence of ataxia. There is no association with the presence of Parkinson
      disease.

PMID- 11594925
TI  - Recognition memory and verbal fluency differentiate probable Alzheimer disease
      from subcortical ischemic vascular dementia.
AB  - BACKGROUND: Alzheimer disease (AD) and vascular dementia are among the most
      frequently occurring causes of dementia in the world, and their accurate
      differentiation is important because different pharmaceutical strategies may
      modify the course of each disease. OBJECTIVE: To determine which of 10
      neuropsychological test scores can accurately differentiate patients with
      probable AD from those with subcortical ischemic vascular dementia (SIVD) for use
      in evidence-based clinical practice. DESIGN: Patients with suspected dementia
      were referred to the study by family physicians, geriatricians, and neurologists.
      All participants received a thorough assessment according to standard diagnostic
      guidelines. Diagnoses of probable AD (n = 31) and probable SIVD (n = 31) were
      made according to consensus criteria. The diagnosticians were blind to the
      results of the 10 neuropsychological test scores. RESULTS: There were no
      significant differences between the groups in age or Mini-Mental State
      Examination scores. Logistic regression analyses identified 2 neuropsychological
      tests that best distinguished the groups (sensitivity = 81%; specificity = 84%;
      positive likelihood ratio = 5.1). These were the recognition memory subtest of
      the Rey Auditory Verbal Learning Test and the Controlled Oral Word Association
      Test. The AD group performed better on the oral association test, whereas the
      SIVD group did better on the recognition memory test. CONCLUSION: Patients with
      probable AD and probable SIVD can be distinguished with a high degree of accuracy
      using these 2 neuropsychological tests.

PMID- 11594926
TI  - Evaluation of dyskinesias in a pilot, randomized, placebo-controlled trial of
      remacemide in advanced Parkinson disease.
AB  - CONTEXT: Long-term levodopa therapy for Parkinson disease commonly results in
      motor complications including "on-off" fluctuations and dyskinesias, but it is
      still unclear how best to assess treatment effects on dyskinesias in clinical
      trials. OBJECTIVE: To compare several methods of rating levodopa-induced
      dyskinesias to evaluate the effect of remacemide hydrochloride treatment in
      patients with advanced Parkinson disease. DESIGN: Two-week multicenter
      randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Five
      academic sites of the Parkinson Study Group. PATIENTS: Thirty-nine subjects at
      least 30 years old with idiopathic Parkinson disease and disabling dyskinesias.
      INTERVENTIONS: Randomly received daily doses of 150 mg, 300 mg, or 600 mg of
      remacemide hydrochloride or matching placebo for 2 weeks. MAIN OUTCOME MEASURES:
      The dyskinesia rating scales used were the Modified Goetz Dyskinesia Rating scale
      (MGDRS), a newly created Lang-Fahn Activities of Daily Living Dyskinesia scale
      (LFADLDS), and diary dyskinesia ratings. RESULTS: Patient and investigator
      diaries showed excellent agreement in dyskinesia ratings. The MGDRS score
      correlated with clinic diary ratings of the percentage of "on" time with
      dyskinesias, and the LFADLDS score correlated with home and clinic diary
      assessments of percentage of on time with severe dyskinesias. The MGDRS score did
      not correlate highly with the LFADLDS score. This pilot study also validated
      previous results demonstrating the safety and tolerability of remacemide
      treatment for advanced Parkinson disease but did not result in any demonstrable
      improvement or worsening in dyskinesia measures. CONCLUSIONS: Diaries may provide
      a valid means of evaluating dyskinesias in clinical trials for Parkinson disease,
      but there remain other aspects of dyskinesias, as assessed by the MGDRS and
      LFADLDS, that are not reflected in diary ratings.

PMID- 11594927
TI  - Dementia, amyotrophy, and periodic complexes on the electroencephalogram: a
      diagnostic challenge.
AB  - BACKGROUND: The clinical diagnosis of neurodegenerative diseases is a challenge
      to the neurologist. In many cases the diagnosis becomes neuropathological only
      after the autopsy. Several consensus criteria have been defined for the clinical
      diagnosis of different neurodegenerative diseases, among them the various types
      of dementia as well as prion-induced diseases. When compared with
      neuropathological findings, these criteria have proved to be reasonably accurate
      for regular practice, research, and epidemiological studies. The problem arises
      when a combination of complementary and clinical data are obtained that do not
      easily match these diagnostic criteria. CASE DESCRIPTION: We describe a patient
      with dementia and periodic complexes on an electroencephalogram, suggesting a
      diagnosis of sporadic Creutzfeldt-Jakob disease. RESULTS: When the condition
      progressed, signs and symptoms of a motoneuron disease appeared. Thus, 2
      different diagnoses were proposed: (1) an amyotrophic variant of a prion-induced
      disease; or (2) an ELA dementia syndrome with periodic complexes on the
      electroencephalogram, a finding that previously has not been described.

PMID- 11594928
TI  - Creutzfeldt-Jakob disease in unusually young patients who consumed venison.
AB  - BACKGROUND: Creutzfeldt-Jakob disease (CJD) in humans and chronic wasting disease
      (CWD) in deer and elk occur in the United States. Recent reports of 3 unusually
      young patients with CJD who regularly consumed deer or elk meat created concern
      about the possible zoonotic transmission of CWD. OBJECTIVE: To examine the
      possible transmission of CWD to humans. PATIENTS: Three unusually young patients
      (aged 28, 28, and 30 years) with CJD in the United States during 1997-2000.
      METHODS: We reviewed medical records and interviewed family members and state
      wildlife and agriculture officials. Brain tissue samples were tested using
      histopathologic, immunohistochemical, immunoblot, or prion protein gene analyses.
      MAIN OUTCOME MEASURES: Presence or absence of established CJD risk factors, deer
      and elk hunting in CWD-endemic areas, and comparison of the evidence for the 3
      patients with that of a zoonotic link between new variant CJD and bovine
      spongiform encephalopathy. RESULTS: None of the patients had established CJD risk
      factors or a history of travel to Europe. Two patients hunted game animals and 1
      was a daughter of a hunter. Unlike patients with new variant CJD, the 3 patients
      did not have a unique neuropathologic manifestation, clinicopathologic
      homogeneity, uniformity in the codon 129 of the prion protein gene, or prion
      characteristics different from those of classic variants. CONCLUSIONS: Although
      the occurrence of 3 unusually young patients with CJD who consumed venison
      suggested a possible relationship with CWD, our follow-up investigation found no
      strong evidence for a causal link. Ongoing CJD surveillance remains important for
      continuing to assess the risk, if any, of CWD transmission to humans.

PMID- 11594929
TI  - Acute disseminated encephalomyelitis associated with hepatitis C virus infection.
AB  - BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an autoimmune
      demyelinating disease of the central nervous system that is frequently preceded
      by an acute viral infection. This is the first reported case of ADEM associated
      with hepatitis C virus (HCV) infection. CASE DESCRIPTION: A 46-year-old woman
      underwent a surgical procedure and received multiple blood transfusions, at which
      time serologic testing for HCV was negative. Fifty days later, she suddenly
      developed seizures, alteration of consciousness, right hemiparesis, hemianopsia,
      and urinary retention. Magnetic resonance imaging revealed symmetric multifocal
      changes on T2-weighted images in the cerebral gray and white matter and in the
      cerebellar white matter with some lesion enhancement after gadolinium
      administration. Blood testing showed a recent HCV infection with high titer of
      IgM early antigens and a strongly positive reaction for HCV RNA. All other
      microbiological and virological test results were negative both in serum and in
      cerebrospinal fluid. Treatment with high-dose dexamethasone was followed by a
      dramatic improvement of the clinical and magnetic resonance picture. Within a few
      months the patient recovered completely and there were no relapses during 2 years
      of follow-up. CONCLUSIONS: Infection with HCV is associated with several
      autoimmune neurological manifestations. It is recommended the patients with ADEM
      be screened for HCV.

PMID- 11594930
TI  - Treatment of ballism and pseudobulbar affect with sertraline.
AB  - BACKGROUND: The pathogenesis of ballism is uncertain and may involve more than
      one mechanism; treatment is not always efficacious. OBJECTIVE: To provide
      evidence of a nondopaminergic mechanism and the potential for a prompt and nearly
      complete response to a serotonergic agent. METHODS: Report of 2 separate trials
      of sertraline hydrochloride in a single patient. RESULTS: Complete remission of
      symptoms within 48 hours of each drug trial. CONCLUSION: Sertraline may offer an
      alternative with a better adverse effect profile than dopamine receptor blockers
      in the treatment of patients with ballism.

PMID- 11594931
TI  - Angioplasty and stenting for primary treatment of intracranial arterial stenoses.

PMID- 11594932
TI  - Angioplasty or stenting is not appropriate as first-line treatment of
      intracranial stenosis.

PMID- 11594933
TI  - Medical and endovascular therapy for intracranial atherosclerotic vascular
      disease.

PMID- 11594934
TI  - Carotid rete mirabile associated with aortic arch anomaly.

PMID- 11594935
TI  - von Economo encephalitis.
AB  - In April 1917, Dr Constantin von Economo presented his clinical and pathologic
      findings of a new disease--soon to be part of a worldwide epidemic--before the
      Vienna Psychiatric Society. He named it encephalitis lethargica. After years of
      careful observation, he collected and analyzed thousands of cases and classified
      them into 3 clinical syndromes: somnolent-ophthalmoplegic, hyperkinetic, and
      amyostatic-akinetic forms. He described the now legendary postencephalitic
      Parkinsonism, noting that symptoms could emerge years after the original
      infection, often without signs of prodromal "flu." He emphasized the
      neuropathologic findings: inflammatory changes in the tegmentum of the midbrain
      accounting for the sleep disturbance and ocular signs. After encountering
      sporadic cases following the epidemic, he concluded that the somnolent
      ophthalmoplegic syndrome was the primary expression of encephalitis lethargica.
      This article outlines the observations and conclusions of Dr von Economo during
      and after the epidemic through seminal quotations primarily from his published
      works, as well as from more recent reports.

PMID- 11594936
TI  - Pseudotumor cerebri.
AB  - Probable cases of pseudotumor cerebri were described more than a hundred years
      ago. A great deal of controversy existed regarding proper terminology and disease
      characterization. The clinical entity was doubtful before the routine use of
      ventriculography in the 1930s. Throughout history, many terms have been used,
      including serous meningitis, pseudotumor cerebri, otitic hydrocephalus,
      angioneurotic hydrocephalus, toxic hydrocephalus, meningeal hypertension,
      hypertensive meningeal hydrops, pseudoabscess, intracranial hypertension of
      unknown cause, papilledema of indeterminate etiology, intracranial pressure
      without brain tumor, benign intracranial hypertension, and idiopathic
      intracranial hypertension.

PMID- 11594937
TI  - The sacred disease of Cambyses II.
AB  - Herodotus' account of the mad acts of the Persian king Cambyses II contains one
      of the two extant pre-Hippocratic Greek references to epilepsy. This reference
      helps to illuminate Greek thinking about epilepsy, and disease more generally, in
      the time immediately preceding the publication of the Hippocratic treatise on
      epilepsy, On the Sacred Disease. Herodotus attributed Cambyses' erratic behavior
      as ruler of Egypt to either the retribution of an aggrieved god or to the fact
      that he had the sacred disease. Herodotus considered the possibility that the
      sacred disease was a somatic illness, agreeing with later Hippocratic authors
      that epilepsy has a natural rather than a divine cause. Archaeological evidence
      suggests Herodotus slanders Cambyses, and there is no corroboration that the
      Persian king had epilepsy or any other disease. However, the view of epilepsy as
      a somatic disease and uncertainty about the cause of madness shows Herodotus as a
      transitional figure between supernatural and naturalistic medical theories.

PMID- 11594938
TI  - Association between lobar-type hemorrhage and amyloid angiopathy.

PMID- 11594940
TI  - Does mild cognitive impairment represent early-stage Alzheimer disease?

PMID- 11594942
TI  - A randomized, placebo-controlled, clinical trial of high-dose supplementation
      with vitamins C and E, beta carotene, and zinc for age-related macular
      degeneration and vision loss: AREDS report no. 8.
AB  - BACKGROUND: Observational and experimental data suggest that antioxidant and/or
      zinc supplements may delay progression of age-related macular degeneration (AMD)
      and vision loss. OBJECTIVE: To evaluate the effect of high-dose vitamins C and E,
      beta carotene, and zinc supplements on AMD progression and visual acuity. DESIGN:
      The Age-Related Eye Disease Study, an 11-center double-masked clinical trial,
      enrolled participants in an AMD trial if they had extensive small drusen,
      intermediate drusen, large drusen, noncentral geographic atrophy, or pigment
      abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1
      eye. At least 1 eye had best-corrected visual acuity of 20/32 or better.
      Participants were randomly assigned to receive daily oral tablets containing: (1)
      antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg);
      (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3)
      antioxidants plus zinc; or (4) placebo. MAIN OUTCOME MEASURES: (1) Photographic
      assessment of progression to or treatment for advanced AMD and (2) at least
      moderate visual acuity loss from baseline (> or =15 letters). Primary analyses
      used repeated-measures logistic regression with a significance level of.01,
      unadjusted for covariates. Serum level measurements, medical histories, and
      mortality rates were used for safety monitoring. RESULTS: Average follow-up of
      the 3640 enrolled study participants, aged 55-80 years, was 6.3 years, with 2.4%
      lost to follow-up. Comparison with placebo demonstrated a statistically
      significant odds reduction for the development of advanced AMD with antioxidants
      plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52-0.98). The
      ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55-1.03) and 0.80
      (99% CI, 0.59-1.09), respectively. Participants with extensive small drusen,
      nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5
      year probability of progression to advanced AMD. Odds reduction estimates
      increased when these 1063 participants were excluded (antioxidants plus zinc: OR,
      0.66; 99% CI, 0.47-0.91; zinc: OR, 0.71; 99% CI, 0.52-0.99; antioxidants: OR,
      0.76; 99% CI, 0.55-1.05). Both zinc and antioxidants plus zinc significantly
      reduced the odds of developing advanced AMD in this higher-risk group. The only
      statistically significant reduction in rates of at least moderate visual acuity
      loss occurred in persons assigned to receive antioxidants plus zinc (OR, 0.73;
      99% CI, 0.54-0.99). No statistically significant serious adverse effect was
      associated with any of the formulations. CONCLUSIONS: Persons older than 55 years
      should have dilated eye examinations to determine their risk of developing
      advanced AMD. Those with extensive intermediate size drusen, at least 1 large
      druse, noncentral geographic atrophy in 1 or both eyes, or advanced AMD or vision
      loss due to AMD in 1 eye, and without contraindications such as smoking, should
      consider taking a supplement of antioxidants plus zinc such as that used in this
      study.

PMID- 11594944
TI  - Risk factors for age-related maculopathy: the Visual Impairment Project.
AB  - OBJECTIVE: To describe the risk factors and associated population attributable
      risk for age-related maculopathy (ARM) and age-related macular degeneration (AMD)
      in Australians aged 40 years and older. METHODS: Residents were recruited from 9
      randomly selected urban clusters and 4 randomly selected rural clusters in
      Victoria, Australia. At locally established test sites, the following information
      was collected: visual acuity, medical and health history, lifetime sunlight
      exposure, dietary intake, and fundus photographs. Age-related maculopathy and AMD
      were graded from the fundus photographs using an international classification and
      grading system. Backwards logistic regression was used to identify the
      independent risk factors for ARM and AMD. RESULTS: The participation rate was 83%
      (n = 3271) among the urban residents and 92% (n = 1473) among the rural
      residents. Gradable fundus photographs of either eye were available for 4345
      (92%) of the 4744 participants. There were 656 cases of ARM, giving a weighted
      prevalence of 15.1% (95% confidence limit [CL], 13.8, 16.4); and there were 30
      cases of AMD, giving a weighted prevalence of 0.69% (95% CL, 0.33, 1.03). In
      multiple logistic regression, the risk factors for AMD were as follows: age (odds
      ratio [OR], 1.23; 95% CL, 1.17, 1.29), smoked cigarettes for longer than 40 years
      (OR, 2.39; 95% CL, 1.02, 5.57), and ever taken angiotensin-converting enzyme
      inhibitors (OR, 3.26; 95% CL, 1.33, 8.01). The magnitude of all of these risk
      factors was slightly less for ARM, and having ever taken blood cholesterol
      lowering medications was also significant (OR, 1.67; 95% CL, 1.12, 2.47; P
      =.001). CONCLUSION: Smoking is the only modifiable risk factor for ARM and AMD,
      among the many environmental and systemic factors that were assessed.

PMID- 11594945
TI  - Light exposure and the risk of age-related macular degeneration: the Pathologies
      Oculaires Liees a l'Age (POLA) study.
AB  - BACKGROUND: The role of light exposure in the development of age-related macular
      degeneration (ARMD) has been questioned. We present the relationship between
      lifetime light exposure and ARMD as examined in the Pathologies Oculaires Liees a
      l'Age (POLA) study. METHODS: The POLA study is a population-based study on
      cataract and ARMD and their risk factors. It included 2584 residents of the town
      of Sete, located in the South of France. The presence of early and late ARMD was
      assessed on the basis of 50 degrees color fundus photographs using an
      international classification system. A questionnaire about light exposure was
      administered. RESULTS: Late ARMD (n = 38) was not significantly associated with
      any light exposure variable. Subjects exposed to high ambient solar radiation and
      those with frequent leisure exposure to sunlight had a decreased risk of
      pigmentary abnormalities (odds ratio [OR] = 0.61; 95% confidence interval [CI],
      0.39-0.93, and OR = 0.70; 95% CI, 0.52-0.95, respectively) and of early signs of
      ARMD (OR = 0.73; 95% CI, 0.54-0.98, and OR = 0.80; 95% CI, 0.64-1.00,
      respectively). Subjects who had used sunglasses regularly had a decreased risk of
      soft drusen (OR = 0.81; 95% CI, 0.66-1.00). These relationships were not modified
      by further adjustments for potential confounders. CONCLUSION: Our study does not
      support a deleterious effect of sunlight exposure in ARMD.

PMID- 11594943
TI  - A randomized, placebo-controlled, clinical trial of high-dose supplementation
      with vitamins C and E and beta carotene for age-related cataract and vision loss:
      AREDS report no. 9.
AB  - BACKGROUND: Experimental and observational data suggest that micronutrients with
      antioxidant capabilities may retard the development of age-related cataract.
      OBJECTIVE: To evaluate the effect of a high-dose antioxidant formulation on the
      development and progression of age-related lens opacities and visual acuity loss.
      DESIGN: The 11-center Age-Related Eye Disease Study (AREDS) was a double-masked
      clinical trial. Participants were randomly assigned to receive daily oral tablets
      containing either antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta
      carotene, 15 mg) or no antioxidants. Participants with more than a few small
      drusen were also randomly assigned to receive tablets with or without zinc (80 mg
      of zinc as zinc oxide) and copper (2 mg of copper as cupric oxide) as part of the
      age-related macular degeneration trial. Baseline and annual (starting at year 2)
      lens photographs were graded at a reading center for the severity of lens
      opacities using the AREDS cataract grading scale. MAIN OUTCOME MEASURES: Primary
      outcomes were (1) an increase from baseline in nuclear, cortical, or posterior
      subcapsular opacity grades or cataract surgery, and (2) at least moderate visual
      acuity loss from baseline (>/=15 letters). Primary analyses used repeated
      measures logistic regression with a statistical significance level of P =.01.
      Serum level measurements, medical histories, and mortality rates were used for
      safety monitoring. RESULTS: Of 4757 participants enrolled, 4629 who were aged
      from 55 to 80 years had at least 1 natural lens present and were followed up for
      an average of 6.3 years. No statistically significant effect of the antioxidant
      formulation was seen on the development or progression of age-related lens
      opacities (odds ratio = 0.97, P =.55). There was also no statistically
      significant effect of treatment in reducing the risk of progression for any of
      the 3 lens opacity types or for cataract surgery. For the 1117 participants with
      no age-related macular degeneration at baseline, no statistically significant
      difference was noted between treatment groups for at least moderate visual acuity
      loss. No statistically significant serious adverse effect was associated with
      treatment. CONCLUSION: Use of a high-dose formulation of vitamin C, vitamin E,
      and beta carotene in a relatively well-nourished older adult cohort had no
      apparent effect on the 7-year risk of development or progression of age-related
      lens opacities or visual acuity loss.

PMID- 11594946
TI  - One-year follow-up of blood-retinal barrier and retinal thickness alterations in
      patients with type 2 diabetes mellitus and mild nonproliferative retinopathy.
AB  - OBJECTIVE: To examine the 1-year alterations of the blood-retinal barrier and
      changes in retinal thickness occurring in the macular region in patients with
      type 2 diabetes mellitus and mild nonproliferative retinopathy. METHODS: We
      classified 12 eyes of 12 patients with type 2 diabetes mellitus and mild
      nonproliferative retinopathy by 7-field stereoscopic fundus photography, levels
      20 and 35 of Wisconsin grading, and examined them 3 times, at 6-month intervals,
      by fluorescein angiography, retinal leakage analyzer (RLA) (modified confocal
      scanning laser ophthalmoscope), and retinal thickness analyzer. The maps of
      retinal leakage and retinal thickness were aligned and integrated into one image.
      Data from the group of individuals with diabetes were compared with those from a
      healthy control population (n = 14; mean age, 48 years; age range, 42-55 years)
      to establish reference maps for the RLA and the retinal thickness analyzer.
      RESULTS: Areas of abnormally increased fluorescein sodium leakage and increased
      thickness were detected in all eyes examined at baseline. The sites of increased
      fluorescein leakage reached values as high as 483% above normal, but in 10 of the
      total 36 examinations performed, fluorescein leakage returned to normal levels. A
      statistically significant correlation was found between changes in hemoglobin
      A(1c) values and variations in percentage of abnormal fluorescein leakage between
      the 6- and 12-month examinations (P<.001). When comparing the RLA-leaking sites
      among the 3 examinations, a good correlation was seen among the location of these
      sites of maximum leakage, but there was a clear fluctuation in the percentage of
      increases. A correlation was noted between the location of the RLA-leaking sites
      and the location of areas of increased retinal thickness in subsequent
      examinations, either 6 or 12 months later. Microaneurysms showed relatively
      little leakage and leaked progressively less in successive examinations.
      CONCLUSIONS: The dominant alteration in the retina of patients with type 2
      diabetes mellitus and mild nonproliferative retinopathy is the presence of RLA
      leaking sites, indicating spotty retinal vascular damage characterized by
      alteration of the blood-retinal barrier. This damage appears to be reversible and
      directly associated with variations in glycemic metabolic control. Retinal edema
      appears to develop mainly as a result of retinal vascular leakage.

PMID- 11594947
TI  - Initial stages of posterior vitreous detachment in healthy eyes of older persons
      evaluated by optical coherence tomography.
AB  - OBJECTIVE: To promote understanding of the development of posterior vitreous
      detachment (PVD) in healthy eyes using optical coherence tomography (OCT).
      METHODS: We studied 209 eyes of 209 healthy volunteers (165 men and 44 women;
      mean age, 52.3 years [range, 31-74 years]). In addition to biomicroscopy and
      ophthalmoscopy, OCT was performed to obtain high-resolution cross-sectional
      images of the vitreoretinal interface in the posterior fundus. RESULTS: The
      condition of the posterior vitreoretinal interface was classified as 1 of 5
      stages, according to biomicroscopic findings and OCT images relative to discrete
      linear signals indicating a detached posterior vitreous face: stage 0, no PVD (61
      eyes [29.2%]); stage 1, incomplete perifoveal PVD in up to 3 quadrants (100 eyes
      [47.8%]); stage 2, incomplete perifoveal PVD in all quadrants, with residual
      attachment to the fovea and optic disc (26 eyes [12.4%]); stage 3, incomplete PVD
      over the posterior pole, with residual attachment to the optic disc (4 eyes
      [1.9%]); or stage 4, complete PVD identified with biomicroscopy, but not with OCT
      because of instrument limitations (18 eyes [8.6%]). Stage 1, 2, and 3 incomplete
      PVD without subjective symptoms was not recognizable on contact lens
      biomicroscopy. There was a significant age-related progression in the condition
      of the vitreoretinal interface from stage 0 to stage 4. The superior quadrant was
      usually the initial site of incomplete PVD. CONCLUSIONS: Optical coherence
      tomography demonstrates that healthy human eyes have incomplete or partial PVD
      beginning as early as the fourth decade of life. Age-related PVD occurs initially
      as a focal detachment in the perifovea of 1 quadrant, with persistent attachment
      to the fovea and optic nerve head, with a predilection for the superior quadrant.
      It extends its range slowly for years and eventually results in complete PVD,
      associated with release of vitreopapillary adhesion.

PMID- 11594948
TI  - Symptoms predictive for the later development of retinal breaks.
AB  - OBJECTIVE: To identify symptoms in patients with isolated posterior vitreous
      detachment predictive for the later development of retinal breaks. METHODS: Two
      hundred eighty consecutive patients seen with symptoms of posterior vitreous
      detachment were prospectively asked to complete a questionnaire detailing their
      symptoms. At the time of presentation and follow-up, all patients had a full
      ophthalmologic examination including slitlamp biomicroscopy with Goldmann 3
      mirror contact lens after maximal pupil dilatation. Two hundred fifty patients
      with an isolated posterior vitreous detachment were included and reexamined 6
      weeks after the onset of symptoms. If small retinal or vitreous hemorrhages were
      detected, patients were reexamined after 2 weeks. RESULTS: In 13 patients (5.2%)
      a retinal break was detected at reexamination. Logistic regression analysis with
      backward elimination revealed that symptoms of flashes in combination with clouds
      or multiple (>10) small dots at the time of the initial examination or an
      increase of floaters after the initial examination were statistically
      significantly (P<.001) related to the development of new breaks. These symptoms
      had a predictive value for the presence or absence of a new retinal break of
      75.0% and 99.6%, respectively. CONCLUSIONS: Specific symptoms can identify
      patients at risk for the development of new retinal breaks after an initial
      examination in which no abnormalities were found and may obviate the need for
      follow-up appointments of patients not at risk.

PMID- 11594949
TI  - Topical treatment of acute adenoviral keratoconjunctivitis with 0.2% cidofovir
      and 1% cyclosporine: a controlled clinical pilot study.
AB  - OBJECTIVE: To evaluate the efficacy of 0.2% cidofovir eyedrops and 1%
      cyclosporine eyedrops administered 4 times daily (qid) to treat acute adenoviral
      keratoconjunctivitis. METHODS: A randomized, controlled, double-masked study was
      conducted on 39 patients with acute adenoviral keratoconjunctivitis of recent
      onset. Patients were divided into 4 treatment groups: (1) cidofovir qid, (2)
      cyclosporine qid, (3) cidofovir + cyclosporine qid, and (4) sodium chloride qid
      (control). The diagnosis was confirmed using adenoviral polymerase chain reaction
      from conjunctival swabs. Duration of treatment was 21 days. MAIN OUTCOME
      MEASURES: Severity of conjunctival hyperemia, conjunctival chemosis, superficial
      punctate keratitis during treatment, and presence and severity of corneal
      subepithelial infiltrates were evaluated using a clinical score. Duration until
      subjective improvement of symptoms was recorded. RESULTS: Subjective improvement
      of local symptoms was accelerated in the cyclosporine group. All other clinically
      relevant variables showed no statistically significant difference among the 4
      treatment groups. Particularly, we did not find a difference in the frequency of
      corneal subepithelial infiltrates at the end of treatment. CONCLUSIONS: Use of
      cidofovir, cyclosporine, or both did not accelerate the improvement of clinical
      symptoms of acute adenoviral keratoconjunctivitis compared with the natural
      course of the infection as demonstrated by this pilot study. This might be
      because of the wide spectrum of the clinical course of the infection, low
      sensitivity to cidofovir, too low of a concentration of cidofovir, or early
      cessation of viral replication in the course of the infection. The effect of a
      higher concentration of topical cidofovir with and without cyclosporine requires
      investigation in a larger group of patients.

PMID- 11594950
TI  - Optic disc and visual field changes in a prospective longitudinal study of
      patients with glaucoma: comparison of scanning laser tomography with conventional
      perimetry and optic disc photography.
AB  - OBJECTIVE: To investigate the relationship between optic disc changes measured
      with scanning laser tomography and those measured with conventional perimetry and
      optic disc photography. METHODS: In a prospective longitudinal study, we followed
      up 77 patients with early glaucomatous visual field damage. Scanning laser
      tomography (using the Heidelberg Retina Tomograph) and conventional perimetry
      (using the Humphrey Field Analyzer) were carried out every 6 months. Disc
      progression was determined by a procedure recently described by us for scanning
      laser tomography, with confirmed progression requiring repeatable changes based
      on probability limits for both the depth (using individual test-retest
      variability values) and size of change (determined in a group of 37 healthy
      individuals also followed up prospectively). Field progression was determined
      with the Statpac Glaucoma Change Probability Analysis. The agreement between
      scanning laser tomography and conventional disc photography was determined in a
      subgroup of patients. RESULTS: Patients were followed up for a median of 5.5
      years, with a median of 12 sets of examinations with scanning laser tomography
      and conventional perimetry. Twenty-one patients (27%) showed no progression with
      either technique. Thirty-one patients (40%) progressed with scanning laser
      tomography only, while 3 (4%) progressed with conventional perimetry only. Of the
      22 patients (29%) who progressed with both techniques, 10 (45%) progressed with
      scanning laser tomography first (median, 18 month earlier) and 9 (41%) with
      conventional perimetry first (median, 12 months earlier), while 3 (14%)
      progressed at the same time. Of the 16 patients with disc photographs that
      closely overlapped the follow-up, there was concordance between scanning laser
      tomography and disc photography in 13 patients (81%). CONCLUSIONS: Glaucomatous
      disc changes determined with scanning laser tomography occur more frequently than
      field changes. Most patients with field changes also had disc changes; however,
      less than half of those with disc changes had field changes.

PMID- 11594951
TI  - "Masked" pseudoexfoliation syndrome in unoperated eyes with circular posterior
      synechiae: clinical-electron microscopic correlation.
AB  - OBJECTIVE: To investigate the prevalence of "masked" pseudoexfoliation (PEX)
      syndrome in eyes with circular posterior synechiae receiving antiglaucomatous
      therapy with miotics. DESIGN: Cross-sectional prospective study. METHODS: Twenty
      eight eyes of 27 consecutive patients with circular posterior synechiae and a
      history of miotic drug use without previous intraocular surgery, inflammation, or
      trauma, and without conventional signs of PEX material in the anterior chamber
      were included in the study. All eyes were investigated by slitlamp biomicroscopy
      and gonioscopy of the anterior chamber before extracapsular cataract surgery for
      the presence of typical PEX-associated iris pigment epithelial changes, such as
      peripupillary atrophy and trabecular meshwork melanin granule deposition. The
      anterior chamber depth, lens thickness, and axial lengths of the eyes were
      measured by A-scan immersion sonography. The excised anterior lens capsules
      obtained during extracapsular cataract surgery were investigated for the presence
      of precapsular fibrillar PEX deposits by electron microscopy. MAIN OUTCOME
      MEASURE: The prevalence of masked PEX syndrome in eyes with circular posterior
      synechiae receiving antiglaucomatous therapy with miotics. RESULTS: Transmission
      electron microscopy of unselected nonserial sections revealed a precapsular layer
      consisting of typical PEX fibers or microfibrils, which indicated early stages of
      PEX syndrome in 18 (64%) of 28 eyes with circular posterior synechiae. Melanin
      granules were frequently found adhering to the fibrillar layer. Eyes with
      precapsular fibrillar deposits showed significantly greater trabecular meshwork
      pigmentation than eyes without such deposits. Differences in age, lens thickness,
      axial length of the eye, anterior chamber depth, and degree of peripupillary
      atrophy were, however, not statistically significant between the groups with and
      without electron microscopic evidence of PEX deposits. CONCLUSIONS: Circular
      posterior synechiae were more frequently associated with manifest or early stages
      of PEX syndrome. However, the formation of broad posterior synechiae in miosis
      prevented a definite clinical diagnosis based on the classic changes of the
      anterior lens capsule. In eyes with spontaneous or miotic-induced circular
      posterior synechiae without other obvious cause, the masked variant of PEX
      syndrome should always be considered.

PMID- 11594952
TI  - Gelatinase B in vernal keratoconjunctivitis.
AB  - OBJECTIVES: To investigate the expression of gelatinase B in the conjunctiva of
      patients with vernal keratoconjunctivitis (VKC) and the cellular source of this
      enzyme. METHODS: Conjunctival biopsy specimens from 12 patients with active VKC
      and 12 control subjects were studied using immunohistochemical techniques and a
      monoclonal antibody against gelatinase B. The phenotype of gelatinase B(+)
      inflammatory cells was examined using double immunohistochemical analysis and
      monoclonal antibodies against eosinophil peroxidase or macrophage CD68.
      Quantitative zymography was used to compare the activity of gelatinase B in
      conjunctival biopsy specimens from 10 patients with active VKC and 7 control
      subjects. RESULTS: Gelatinase B was detected in a few polymorphonuclear cells in
      8 control specimens. All VKC specimens showed gelatinase B immunoreactivity in
      the epithelial and stromal inflammatory infiltrate. Compared with control
      specimens, VKC specimens showed significantly more gelatinase B-positive cells
      (mean +/- SD, 40.8 +/- 29.9 vs 10.3 +/- 2.4; P<.02). Most gelatinase B-positive
      cells were eosinophils (90.2% +/- 3.6%). Zymography revealed that gelatinase B
      levels in VKC specimens were significantly higher than the levels found in normal
      conjunctiva (3780.3 +/- 3541.0 vs 610.1 +/- 397.1 scanning units; P<.03).
      CONCLUSIONS: These findings suggest overexpression of gelatinase B by eosinophils
      in VKC specimens and participation of gelatinase B in the pathologic changes in
      VKC. CLINICAL RELEVANCE: Control of the release and/or activation of gelatinase B
      in eosinophils may provide a new therapeutic strategy for treating VKC.

PMID- 11594953
TI  - Effects of cyclosporin A on human conjunctival fibroblasts.
AB  - OBJECTIVE: To evaluate the effects of cyclosporin A (CsA) on cytokine and/or
      collagen production, cell growth, and apoptosis in conjunctival fibroblast
      cultures. METHODS: Fibroblast cultures derived from normal subjects and patients
      with vernal keratoconjunctivitis and pemphigoid were exposed to different
      concentrations of CsA for either 24 hours or 30 days. The effects were evaluated
      by the colorimetric MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium
      bromide) test to assess cell proliferation, and by the measurement of procollagen
      I (PIP) and procollagen III (PIIIP) cytokines and total protein in culture
      medium. CsA-induced apoptosis was assessed by fluorescence-activated cell sorter
      analysis. RESULTS: After 24 hours of exposure to doses of CsA of more than 10
      microg/mL, cell proliferation and migration were significantly reduced.
      Cyclosporin A reduced PIP and interleukin 1 (IL-1) production in a dose-dependent
      manner. Interleukin 6 and IL-8 were increased by 10 microg/mL of CsA, whereas
      transforming growth factor beta, PIIIP, and total protein were unaffected.
      Cyclosporin A exposure induced apoptosis in a time- and dose-dependent manner.
      Long-term exposure to CsA reduced IL-6 but did not modify PIIIP production.
      CONCLUSION: Exposure to CsA directly modified fibroblast behavior. CLINICAL
      RELEVANCE: Cyclosporin A ability to accelerate apoptosis in clinically fibrotic
      tissues may prove to be therapeutic and useful in hyperproliferative conjunctival
      disorders.

PMID- 11594954
TI  - Pharmacokinetics and toxicity of intravitreal chemotherapy for primary
      intraocular lymphoma.
AB  - OBJECTIVE: To investigate the pharmacokinetics and toxicity of intravitreal
      chemotherapeutic agents in the rabbit eye for the potential treatment of primary
      intraocular lymphoma and other intraocular malignancies. METHODS: The ocular
      pharmacokinetics of intravitreal methotrexate sodium (400 microg) was studied in
      10 New Zealand white rabbits, and a single-compartment, first-order elimination
      model was used to calculate the drug half-life. With the use of these data, a
      treatment schedule using serial injections of intravitreal methotrexate and
      single injections of fluorouracil and dexamethasone sodium phosphate was
      developed. This schedule was studied in 4 New Zealand white rabbits to explore
      the combined toxicity of these agents. RESULTS: Methotrexate vitreous levels,
      following a 400-microg intravitreal injection, remained therapeutic (>0.5 microM)
      in the rabbit eye for 48 to 72 hours. Intravitreal methotrexate, combined with
      fluorouracil and dexamethasone, showed no evidence of drug toxicity as determined
      by electroretinography and histopathologic examination. CONCLUSIONS: A treatment
      schedule for primary intraocular lymphoma consisting of methotrexate intravitreal
      injections every 48 to 72 hours provides therapeutic drug concentrations in the
      vitreous and, in combination with fluorouracil and dexamethasone, appears to be
      safe in the rabbit eye. CLINICAL RELEVANCE: Although responsive to conventional
      chemotherapy or radiotherapy, recurrence of ocular involvement with primary
      central nervous system lymphoma occurs in more than 50% of treated cases.
      Anecdotal reports of the use of intravitreal chemotherapy for primary intraocular
      lymphoma have been encouraging. However, animal data on the pharmacokinetics and
      toxicity of combined intravitreal agents for the treatment of this disease are
      lacking.

PMID- 11594955
TI  - Ocular manifestations in children born after in vitro fertilization.
AB  - OBJECTIVE: To report the ocular abnormalities found in children born after in
      vitro fertilization. METHODS: Forty-seven children (25 girls and 22 boys) born
      after an in vitro fertilization pregnancy (mean +/- SD birth weight, 2335 +/- 817
      g; range, 924-4300 g) and referred for ophthalmic evaluation were included in the
      study. All underwent a thorough ocular examination. Obstetric history was
      gathered following a detailed questionnaire with the mothers. RESULTS: Of 70 eyes
      among nonverbal children, visual acuity was "normal for age" in 60 (86%), "fair"
      in 4 (6%), and "poor" in 6 (9%). Visual acuity in 24 eyes in verbal children
      ranged from 6/6 to no light perception, with 4 (17%) having poor vision.
      Cycloplegic refraction disclosed an emmetropia in 22 (27%), hypermetropia in 47
      (57%), and myopia in 13 (16%) of the eyes. Anisometropia of more than 1.0
      diopters was found in 8 children. Major ocular malformations were observed in 12
      (26%) of the 47 children. These malformations included Coats disease, congenital
      cataract, congenital glaucoma, hypoplastic optic nerve head, idiopathic optic
      atrophy, coloboma with microphthalmos, and retinoblastoma. CONCLUSIONS: Ocular
      anomalies were frequently observed in this cohort of offspring born after in
      vitro fertilization. A diligent and prospective prenatal search for such
      malformations should unveil the real prevalence of ocular malformations in
      children born after in vitro fertilization.

PMID- 11594956
TI  - Thomas Colledge: a pioneering British eye surgeon in China.

PMID- 11594957
TI  - Antioxidants, zinc, and age-related macular degeneration: results and
      recommendations.

PMID- 11594958
TI  - Ophthalmology in Israel.

PMID- 11594959
TI  - Ophthalmology in Russia.

PMID- 11594960
TI  - Ophthalmology in the Kingdom of Saudi Arabia.

PMID- 11594962
TI  - Traumatic hyphema and factor XI deficiency (hemophilia C).

PMID- 11594961
TI  - Ultrasound biomicroscopy of an implantable miniaturized telescope.

PMID- 11594963
TI  - Hereditary motor and sensory neuropathy associated with juvenile glaucoma.

PMID- 11594965
TI  - Bilateral central retinal vein occlusion in a patient with occult colon cancer.

PMID- 11594964
TI  - Retinal periphlebitis as zoster sine herpete.

PMID- 11594966
TI  - Japanese X-linked juvenile retinoschisis: conflict of phenotype and genotype with
      novel mutations in the XLRS1 gene.

PMID- 11594967
TI  - Wilson disease.

PMID- 11594968
TI  - Transcorneal tube erosion of an Ahmed valve implant in a child.

PMID- 11594969
TI  - "Eye-tooth": a case of orbital dentigerous cyst after trauma.

PMID- 11594970
TI  - Women in ophthalmology at Wills Eye Hospital.

PMID- 11594971
TI  - The presence of cataract as a predictor of mortality.

PMID- 11594974
TI  - Developing the peer review system of Acta Ophthalmologica.

PMID- 11594973
TI  - Renal-coloboma syndrome in a Brazilian family.

PMID- 11594975
TI  - The therapeutic effects of retinal laser treatment and vitrectomy. A theory based
      on oxygen and vascular physiology.
AB  - The physiologic mechanism of photocoagulation can been seen in the following
      steps. The physical light energy is absorbed in the melanin of the retinal
      pigment epithelium. The adjacent photoreceptors are destroyed and are replaced by
      a glial scar and the oxygen consumption of the outer retina is reduced. Oxygen
      that normally diffuses from the choriocapillaris into the retina can now diffuse
      through the laser scars in the photoreceptor layer without being consumed in the
      mitochondria of the photoreceptors. This oxygen flux reaches the inner retina to
      relieve inner retinal hypoxia and raise the oxygen tension. As a result, the
      retinal arteries constrict and the bloodflow decreases. Hypoxia relief reduces
      production of growth factors such as VEGF and neovascularization is reduced or
      stopped. Vasoconstriction increases arteriolar resistance, decreases hydrostatic
      pressure in capillaries and venules and reduces edema formation according to
      Starling's law. Vitrectomy also improves retinal oxygenation by allowing oxygen
      and other nutrients to be transported in water currents in the vitreous cavity
      from well oxygenated to ischemic areas of the retina. Vitrectomy and retinal
      photocoagulation both improve retinal oxygenation and both reduce diabetic
      macular edema and retinal neovascularization.

PMID- 11594976
TI  - The prevalence and causes of bilateral and unilateral blindness in an elderly
      urban Danish population. The Copenhagen City Eye Study.
AB  - PURPOSE: To study the prevalence and causes of bilateral and unilateral blindness
      in an elderly urban Danish population. METHODS: Data originated from a Danish
      epidemiologic cross-sectional random sample population eye survey conducted
      during the years 1986-1988. The population consisted of 1,000 inhabitants aged 60
      to 80 years in Copenhagen. The participants underwent an extensive ophthalmologic
      examination. A participation rate of 96.9% was achieved. Any blindness was
      defined as best-corrected visual acuity (VA) worse than 0.05 (the WHO criteria)
      and VA of 0.1 or worse (the National criteria (NC) of blindness). RESULTS: The
      prevalence rates of bilateral and unilateral blindness were, respectively, 0.53%
      and 3.38% according to WHO, but 1.06% and 4.44% using NC. Bilateral blindness
      rose significantly with age (p=0.02). According to NC, age-related macular
      degeneration (AMD) was the leading cause of bilateral blindness, accounting for
      60% of all blind persons. Glaucoma, myopic macular degeneration, cataract and
      retinitis pigmentosa were jointly the second most common cause, each accounting
      for 10% of all bilaterally blind persons. Diabetic retinopathy was not a cause of
      bilateral blindness. Amblyopia was the most frequent, AMD the second most
      frequent, and diabetic retinopathy was among the third most common cause of
      unilateral blindness accounting for, respectively, 28.60%, 16.66% and 9.52% of
      all unilateral blindness. CONCLUSIONS: Blindness was associated with increasing
      age. A calculation indicates that among Danes aged 60 to 80 years 7,736 are
      bilaterally blind and 35,503 suffer from unilateral blindness. This study
      highlights AMD as the most important cause.

PMID- 11594977
TI  - Visual impairment in adult people with moderate, severe, and profound
      intellectual disability.
AB  - PURPOSE: To assess visual impairment in adults with intellectual disability after
      de-institutionalisation. PATIENTS: The county has a population of 385 483 persons
      of 18 years and older; 961 were moderately, severely or profoundly intellectually
      impaired (ID), 837 of them (87 %) participated in the investigation. METHODS:
      Visual acuity, VA: Osterberg picture charts and reduced copies for near vision
      could be used in 71% of the patients. Teller preferential looking procedure was
      applied to people who were unable to cooperate with the picture charts. When
      examined with picture wall chart VA 0.3-> or =0.10) was found in 10.8%, severe
      low vision in 1.2% (VA <0.10-> or =0.05), and blindness (VA<0.05) in 3.8%. Poor
      near vision (<0.3) was present in 19%. Those assessed with Teller acuity cards
      had poorer vision than the others. It is possible that the low values of
      assessment with Teller cards represent a combination of gnostic and resolution
      deficiencies, which means that the results of grating VA and recognition VA are
      non-comparable. Ophthalmic disorders: The most widespread medical condition was
      cerebral visual impairment, the most frequent eye disorders were optic atrophy,
      high myopia, cataract, and keratoconus. Refraction: Refraction was assessed in
      710 persons (85%), the most prevalent cause of visual impairment was uncorrected
      ametropia. Hypermetropia of >+1.50 was found in 151 of 710 subjects (21%), and
      spectacles were used by 106 (15%); myopia <-1.0 was present in 213 individuals
      (30%), 95 persons (13%) had lenses <-1.0. CONCLUSION: Resettled adult people with
      intellectual disability have a high prevalence of treatable visual impairment. A
      structured scheme of referral to optometric and ophthalmological care is
      essential if these people are to be given the care to which they are entitled.

PMID- 11594978
TI  - Timolol increased retrobulbar flow velocities in untreated glaucoma eyes but not
      in ocular hypertension.
AB  - PURPOSE: To investigate retrobulbar blood flow velocities and the effects of
      topical timolol treatment in eyes with newly detected, previously untreated open
      angle glaucoma or ocular hypertension. METHODS: Fifteen eyes with open angle
      glaucoma (OAG) and 12 eyes with ocular hypertension (OH), in the same number of
      patients, all untreated and newly detected, were examined with colour Doppler
      imaging of retrobulbar vessels before and after 1 month of topical timolol
      treatment (0.5% Timoptic BID). RESULTS: Baseline central retinal artery end
      diastolic velocity was lower (48%, p=0.0002) and resistive index higher (7.6%,
      p=0.018) in the OAG group than in the OH group. In the glaucoma group mean end
      diastolic velocity increased by 41%, (p=0.006) while resistive index decreased by
      5.8%, (p=0.02) on treatment, while no significant changes were seen in the OH
      group. Blood flow velocities in the ophthalmic artery did not change with
      treatment. Baseline IOP and IOP reduction did not differ between OAG and OH
      group. CONCLUSION: Peripheral resistance to blood flow was found to be increased
      in untreated glaucoma eyes as compared to a similar group of eyes with ocular
      hypertension. Timolol treatment diminished resistance significantly in the
      glaucoma group, but not in the ocular hypertension group. Thus the two groups
      responded differently to timolol treatment. The reaction to IOP lowering
      treatment could indicate defective autoregulation in the glaucoma group.

PMID- 11594979
TI  - Glaucoma in East Greenlandic Inuit--a population survey in Ittoqqortoormiit
      (Scoresbysund).
AB  - PURPOSE: To determine the prevalence of primary angle-closure glaucoma (PACG) in
      an isolated Greenlandic Inuit community and to examine the anatomical risk
      factors for this disease. METHODS: All individuals aged > or =40 years were
      examined. Visual acuity, refractive error, anterior chamber depth (ACD),
      intraocular pressure (IOP), gonioscopy, and optic disc characteristics were
      recorded. RESULTS: Seventy-nine individuals (65% response rate) were examined.
      Mean IOP was 12.0 mmHg. ACD was shallow and decreased with age and hypermetropia.
      ACD was deeper than observed in the same community in 1981 and another East
      Greenland population in 1970. Two subjects had definite PACG (2.5 %). CONCLUSION:
      This is the first study to use applanation tonometry in a Greenland population
      and confirms a low IOP as found in other populations of Inuit and Mongolians. ACD
      measured in 1998 was deeper than in 1981 in the same community which may
      represent a cohort effect indicating a secular change.

PMID- 11594980
TI  - Localised changes in glaucomatous visual fields after trabeculectomy.
AB  - BACKGROUND AND OBJECTIVE: Modern techniques of automated perimetry have shown
      that surgical reduction of intraocular pressure (IOP) may have a beneficial
      effect on the glaucomatous visual field. The purpose of the present study was to
      analyse and quantify the changes in the visual fields of glaucoma patients after
      trabeculectomy. MATERIALS AND METHODS: Octopus visual fields of twenty-seven
      glaucoma patients were analysed. Change in visual field mean sensitivity (MS) was
      calculated to detect total field changes. A clinical and a statistical analysis
      of small clusters of test points were used to define whether local changes had
      occurred. RESULTS: MS in the operated eyes improved significantly from 16.4+/-5.6
      to 18.2+/-5.5 dB. The patients had on average 3.9+/-6.2 clusters where the
      retinal sensitivity had improved at least 5 dB and only 0.4+/-0.9 clusters where
      sensitivity had deteriorated at least 5 dB after trabeculectomy. 17 patients had
      more improved than deteriorated clusters postoperatively. CONCLUSION:
      Statistically significant improvement was seen in the MS, but improvement was
      also found in small local areas of the visual fields after trabeculectomy.

PMID- 11594981
TI  - Long-term visual results following primary trabeculectomy for infantile glaucoma.
AB  - PURPOSE: To report the long-term visual outcome of eyes that underwent primary
      trabeculectomy for infantile glaucoma and to evaluate factors that affect visual
      prognosis. METHODS: Thirty-five eyes of 22 consecutive patients presenting
      between 1980 and 1995 were included. Visual acuity, visual fields and refractive
      status were assessed and patient records reviewed. RESULTS: Nineteen of 22
      patients (86.3%) achieved 6/12 or better, (21 of 35 eyes; 60%). Reasons for
      decreased vision included amblyopia (5 eyes), field loss (4 eyes), corneal
      opacification (2 eyes), and uncontrolled IOP (1 eye). Primary glaucoma had a
      better outcome than secondary glaucoma. Vision was frequently unequal despite
      controlled pressure, clear media and full fields in both eyes. This was
      associated with myopic anisometropia and apparent amblyopia. Ten patients
      responded to patching. Eyes with field defects were unresponsive to patching.
      CONCLUSIONS: Field defects, corneal scarring, marked anisometropia and severe
      astigmatism result in poor vision. Anisometropic amblyopia is frequently present
      and responds well to patching. Visual outcome is dependent on early and sustained
      control of intraocular pressure and aggressive treatment of amblyopia.

PMID- 11594982
TI  - Pseudoexfoliation syndrome in eyes with ischemic central retinal vein occlusion.
      A histopathologic and electron microscopic study.
AB  - PURPOSE: To determine histopathologically the prevalence of pseudoexfoliation
      (PEX) material in eyes enucleated secondary to ischemic central retinal vein
      occlusion (CRVO) and to evaluate eyes with PEX material in the anterior segment
      and CRVO ultrastructurally for PEX deposits in the vicinity of central retinal
      vessels. These deposits could explain an association of CRVO and PEX. METHODS:
      All surgically enucleated eyes with secondary angle closure glaucoma due to
      rubeotic iris secondary to ischemic CRVO (1981-1998) available were re-analyzed
      light microscopically for the presence of PEX in the anterior segment (n=120;
      76.9+/-8.5 years [range: 51-91]). Eyes with PEX in the anterior segment and
      available optic nerve cross sections were examined by electron microscopy for PEX
      material in the retrolaminar (n=7) and intralaminar central retinal vessels
      (n=3). All eyes surgically enucleated because of malignant melanoma of the
      choroid aged 70 years and older (1981-1998) with sections available served as age
      matched controls (n=107; 76.4+/-5 years [range: 70-91]). RESULTS: PEX material
      was present light microscopically in the anterior segment in 12 of 120 eyes with
      CRVO (10%) compared to 2 of 107 age-matched eyes with choroidal malignant
      melanoma (1.9%; p<0.05). Electron microscopically, neither structural alterations
      of the vessel wall nor PEX deposits were found in association with central
      retinal vessels both in the intra- and retrolaminar areas in any of the 7 eyes
      with PEX in the anterior segment and CRVO analyzed. CONCLUSIONS:
      Histopathologically, PEX is significantly more common in eyes enucleated
      secondary to CRVO compared to eyes enucleated because of an intraocular tumor.
      This most likely is due to the secondary open angle glaucoma in eyes with PEX as
      a known risk factor for CRVO. According to the small number of optic nerves
      analyzed here, there seems to be no morphologically evident PEX vasculopathy in
      the central retinal vessels both within and immediately behind the lamina
      cribrosa in eyes with PEX in the anterior segment and CRVO potentially causing
      retinal venous thrombosis.

PMID- 11594983
TI  - Contact lens induced keratitis associated with contact lens wear.
AB  - PURPOSE: To evaluate clinical characteristics, risk factors, management and
      outcome of contact lens induced keratitis (CLIK) associated with contact lens
      wear. METHODS: The study comprised all consecutive patients presenting with
      contact lens related presumed microbial keratitis during a 12-month period at our
      department. Detailed demographic data, type of contact lens, duration of lens
      wear, wearing schedule and lens hygiene were derived from a self-administered
      questionnaire. Severity of ulcer, corneal scrapings, treatment and final outcome
      were evaluated. RESULTS: 27 patients with CLIK, some of which may have been
      sterile peripheral infiltrates, due to contact lens wear were detected. In the
      majority of the cases patients had used disposable soft contact lenses (89%) and
      most of them had a daily wearing schedule (78%). 51.8% patients cleaned their
      lenses regularly. 6 (22%) applied no disinfection since their lenses were
      disposable on removal. In 3 of our cases with CLIK, penetrating keratoplasty had
      to be performed. CONCLUSION: Disposable contact lenses seem to have been a
      predisposing factor for contact lens induced keratitis also when used on a daily
      wear schedule. Insufficient contact lens care products and/or manufacturing
      characteristics may be responsible for CLIK, which is also observed in otherwise
      compliant contact lens users. In 3 of our patients with CLIK keratoplasty became
      necessary, indicating that contact lens induced keratitis may result in severe
      corneal complications.

PMID- 11594985
TI  - Cellular proliferation and leukocyte infiltration in the rabbit cornea after
      photorefractive keratectomy.
AB  - PURPOSE: To map the proliferative activity of corneal cells during wound healing
      following photorefractive keratectomy (PRK) and to compare two markers for
      proliferation. METHODS: PRK, 5- mm in diameter with a -6 D setting, was performed
      in one eye of 28 New Zealand White Rabbits. The rabbits were sacrificed at time
      points between 12 hours and three months after surgery. The treated and fellow
      corneas were fixed in 10% formaldehyde, paraffin embedded, and
      immunohistochemically stained for proliferate cell nuclear antigen (PCNA) and at
      one time point, 1 week, also for Ki-67. RESULTS: Following initial sliding of the
      epithelial cells, the proliferative activity in the wound area starts in the
      leading edge (24 hours) and is spread towards the periphery. The proliferative
      activity peaks after one week and subsides during the following two weeks. Early
      (24 hours) proliferative activity is also seen in the limbal epithelium which
      peaks after three days. The keratocytes express PCNA in the peripheral stroma 48
      hours after injury. They then also migrate to repopulate the stroma under the
      wound area. The expression period lasts 1 week and subsides the following week.
      Leukocytes are found in the wound as early as 12 hours after injury. The cells
      disappear around the time of epithelial wound closure, i.e. after 3 days. The two
      proliferative markers PCNA and KI 67 show a similar distribution after surgery.
      CONCLUSION: Epithelial proliferative activity starts earlier after injury, and is
      preceded by leukocyte presence in the wound. The PCNA expression starts later in
      the keratocytes but lasts somewhat longer (3 weeks). PCNA expression appears more
      efficient than Ki-67 to show proliferative activity of slow cycling cells in the
      cornea

PMID- 11594984
TI  - Immunohistological study of infiltrated cells and cytokines in murine herpetic
      keratitis.
AB  - PURPOSE: To identify localization and kinetics of infiltrated cells and cytokines
      in murine herpetic keratitis. METHODS: HSV-1 was inoculated onto the scarified
      BALB/c corneas. At given times post infection (PI), eyes were removed and studied
      immunohistochemically using monoclonal antibodies against several infiltrated
      cells and cytokines. RESULTS: Neutrophils and NK cells infiltrated as early as 1
      day PI reaching a maximum number at 2 day PI in initial stage. gamma delta TCR
      positive cells were observed in the corneal stroma from 1 day PI to 8 day PI. IL
      2 and IFN-gamma were positive in the cell-infiltrated areas of the epithelial and
      stromal lesions, whereas IL-4 was negative throughout the experiment. CONCLUSION:
      Our results indicated that cytokine profile upon herpes infection on the cornea
      is Th1 dominant. Together with neutrophils in the early phase of infection, gamma
      delta positive T cells may play an additional role in protecting the cornea
      against incoming pathogens.

PMID- 11594986
TI  - Influence of laser irradiation on endogenous hyaluronan in rabbit iris and
      aqueous humor.
AB  - PURPOSE: To monitor changes of endogenous hyaluronan in the iris tissue and
      aqueous humor after an isolated trauma to the iris by argon laser irradiation of
      the anterior surface of the iris. METHODS: Iris and aqueous hyaluronan
      concentrations in rabbit were measured with a radiometric assay at different time
      points after laser irradiation. RESULTS: Total hyaluronan content in iris tissue
      increased 3-fold to a peak concentration of 71-72 microg/g at 1 and 2 days after
      laser treatment. Aqueous hyaluronan increased to a maximum of about 1.6 microg/ml
      at 2 h and 12 h after laser irradiation of the iris. CONCLUSIONS: The iris tissue
      responds with increased hyluronan synthesis to an isolated iris argon laser
      irradiation and it seems to be the most important source of aqueous hyaluronan.

PMID- 11594987
TI  - Electroretinogram contact lens electrode with tri-color light-emitting diode.
AB  - PURPOSE: This study was performed to evaluate a new electroretinogram (ERG)
      contact lens electrode containing four light-emitting diodes (LEDs) that are used
      for both stimulus and background light. METHODS: The luminance of each LED could
      be changed independently and used as stimulus light. Red, blue, bright white, and
      flickering ERGs were recorded in 12 normal subjects and two patients with
      progressive cone dystrophy. The long-duration light stimuli separated the on- and
      off-responses of the ERG. This equipment is not according to the ISCEV standard.
      RESULTS: The tri-color LED electrode contact lens can efficiently produce and
      record ERG responses. Off-responses were recordable separately from on-responses
      by lengthening the stimulus duration. CONCLUSION: This combined stimulus
      electrode system is compact and portable. Combined with the portable amplifier
      and the recorder, the ERGs can be recorded easily in an operating room, at
      patients' bedside, and in remote locations away from clinics and hospitals.

PMID- 11594988
TI  - The regional distribution of diabetic retinopathy lesions may reflect risk
      factors for progression of the disease.
AB  - BACKGROUND: Diabetic retinopathy is graded by semi-quantitative assessment of the
      morphological lesions as seen on fundus photographs. This grading method mainly
      considers the type and number of retinopathy lesions, implying that the
      diagnostic value of the regional distribution of retinopathy lesions is largely
      unknown. DESIGN AND METHODS: Case control design. The study group consisted of
      fifteen diabetic patients successively examined in a screening clinic, with
      retinopathy lesions predominantly around the larger vascular arcades. The control
      group consisted of fifteen patients pairwise matched with the patients in the
      study group regarding sex, age, diabetes type, and diabetes duration. The two
      groups were compared with respect to the distribution of individual retinal
      lesions (microaneurysms/dot haemorrhages, blot haemorrhages, cotton wool spots,
      and hard exudates) around the larger vascular arcades and in the macular area,
      hypertensive vascular abnormalities (crossing phenomena, arteriolar narrowing,
      arteriolar light reflex), metabolic regulation, and blood pressure. RESULTS: The
      patients in the study group had significantly more microaneurysms and
      haemorrhages around the larger vascular arcades than had the control group, but
      there was no difference between the vascular changes in the two groups. The study
      group had significantly higher blood pressure than had the control group, whereas
      there was no significant difference in metabolic regulation between the two
      groups. CONCLUSIONS: The findings suggest the existence of a hypertensive-like
      retinopathy in diabetic patients with lesions mainly around the larger vascular
      arcades, but with no increase in hypertensive vascular changes. This pattern is
      not identified with current semi-quantitative grading methods. Further
      improvement of clinical decisions made from fundus photographs of diabetic
      retinopathy requires the development of computerised methods for quantitative
      assessment of retinal lesions.

PMID- 11594989
TI  - Octyl 2-cyanoacrylate tissue adhesive in experimental scleral buckling.
AB  - PURPOSE: In this experimental study, a sutureless scleral buckling was performed
      by using a tissue adhesive glue to fixate a silicone band to the sclera. In fact,
      one of the major risks of traditional scleral buckling is accidental perforation
      of the bulb, which is more frequent when the sclera is extremely thin as it is in
      newborns or in eyes with high myopia or scleromalacia. METHODS: An encircling
      band of silicone, which is generally anchored to the sclera itself, was sutured
      in 36 rabbit eyes to three small silastic patches that had been glued to the
      sclera, at the level of the equator, using octyl 2-cyanoacrylate tissue adhesive.
      In this manner the anchoring sutures passed through silicone and silicone. The
      band was tightened to produce buckling of the sclera and its ends were glued
      together using the same adhesive. RESULTS: Examination of the eyes from 15 days
      to 6 months after surgery revealed that the buckle was stable, with no signs of
      slippage, in 33 eyes. In the remaining 3 (one examined after 15 days, 2 examined
      after 45 days), one of the three support patches had become detached but there
      was still no evidence of slippage. CONCLUSIONS: The stability of the buckle up to
      six months after surgery suggests that this new adhesive might be used for
      sutureless surgery in certain types of retinal detachment, such as that
      associated with stage 4 ROP in which the encircling band has to be removed after
      several months.

PMID- 11594990
TI  - Experimental transplantation of autologous iris pigment epithelial cells to the
      subretinal space.
AB  - PURPOSE: To investigate the cellular morphology in the subretinal space following
      transplantation of iris pigment epithelial (IPE) cells from the same eye.
      METHODS: Following an iridectomy, fresh IPE cells were prepared and no culturing
      performed. After pars plana vitrectomy, a suspension of autologous IPE cells was
      injected into the subretinal space in 37 rabbits. The grafts were monitored by
      ophthalmoscopy and colour fundus photography. Rabbits were sacrificed at 1, 2, 3
      and 6 months, respectively, and the eyes examined with light and electron
      microscopy. RESULTS: The grafted area retained the same configuration over 6
      months but then appeared less pigmented. At 1-3 months, the IPE formed one or
      more contiguous layers on top of native RPE. At 6 months, cells compatible with
      grafted IPE were present in the subretinal space, often forming monolayer-like
      chains integrating with the native RPE. Depigmented cells of presumed IPE origin
      were seen and frequently in association with abundant melanin granules located in
      the apical portion of adjacent RPE cells. In such areas, large macrophage-like
      cells were observed. CONCLUSION: Transplanted IPE cells survived for up to 6
      months in the subretinal space. Our observations suggest a scenario of
      remodelling of the cellular layers in the subretinal space over time where
      grafted IPE cells formed a compound layer with the native RPE. Transplantation of
      autologous IPE cells may have a potential as a treatment modality in selected
      cases of age-related macular degeneration.

PMID- 11594991
TI  - Strabismus surgery: fibrin glue versus vicryl for conjunctival closure.
AB  - PURPOSE: The aim of present study was to compare the results of conjunctival
      closure by fibrin glue with vicryl in strabismus surgery. METHODS: 19 patients
      undergoing bilateral symmetrical strabismus surgery were included in this study.
      Conjunctival incisions were closed with 6-0 vicryl in the right eye and fibrin
      glue in the left eye. RESULTS: On first post-operative day 15 out of 19 eyes
      (78.9%) had well apposed conjunctiva, 3 out of 19 eyes (15.79%) had 1 mm
      retraction and one out of 19 eyes (5.26%) had 2 mm retraction, which needed
      suturing, in cases in which fibrin glue was applied. Increased discomfort and
      excessive watering was noted during the early postoperative period in 8 out of 19
      eyes (42.1%), in eyes in which the conjunctiva was closed with 6-0 vicryl, as
      compared to none in the fibrin glued eyes (p=0.005). However, the difference
      disappeared after 21 days. CONCLUSION: Fibrin glue can be used as an alternative
      to suturing for conjunctival closure following strabismus surgery.

PMID- 11594992
TI  - Data reliability and structure in the Swedish National Cataract Register.
AB  - PURPOSE: A Swedish National Cataract Register was instituted in 1992, monitoring
      nearly all cataract operations in Sweden, and since its inception comprising
      about 95% of all operations. Data from a total of approximately 290 000
      operations have been collected during 1992-1998. Data quality is an important
      factor, and we have therefore assessed the various types and frequencies of data
      entry errors in the material. METHODS: The medical records for all operations in
      five selected participating clinics were retrieved for a set month. Each data
      transfer step from the record to the final data base was monitored for a total of
      574 operations. A total of 10 variables were recorded for each operation.
      RESULTS: Significant sources of error were absent in most variables. However,
      possibly important errors appeared in three: "date entering waiting list",
      "preoperative best corrected visual acuity in the operated eye", or "visual
      acuity in the fellow eye". There were also noteworthy variations between the five
      clinics, different for different parameters. Errors were predominantly prone to
      appear at the very first step of registration. In most cases this was due to
      deviations from the data collection instructions. CONCLUSIONS: The reliability is
      good for most values entered into the register, but it is important to ensure
      that data definitions are exact and adhered to. Repeated information to the
      involved persons on how to fill in the forms appears to be a requisite for
      maintaining good input quality.

PMID- 11594993
TI  - Different clinical expressions in two families with Stargardt's macular dystrophy
      (STGD1).
AB  - PURPOSE: To describe the clinical expressions, with emphasis on
      electrophysiological examinations, in two Swedish families with Stargardt's
      macular dystrophy (STGD1). METHODS: Two pairs of siblings with STGD1, for whom
      diagnosis had been confirmed by genetic linkage to the ABCA4 gene region, were
      examined regarding visual acuity, kinetic perimetry, fundus photography, full
      field ERG and multifocal ERG (MERG). Possible disease-causing mutations were
      screened for by DNA sequencing of selected regions of the ABCA4 gene. RESULTS:
      All STGD1 patients had visual acuity 0.07-0.1. The two families presented
      different fundus appearances, MERGs and implicit times on 30 Hz flicker white
      light full-field ERGs. Genetic analysis revealed one unique sequence variation in
      exon 19 of the ABCA4 gene, in one allele from the patients of one of the
      families. This point mutation causes the amino acid substitution T972N in the
      ABCR protein. CONCLUSION: Two pairs of siblings with STGD1 presented two
      different expressions of the disease regarding the distribution of the retinal
      dysfunction. One possible molecular explanation to the different clinical
      expressions may be the T972N substitution present in the ABCR protein in one of
      the STGD1 families investigated.

PMID- 11594994
TI  - Spider keratouveitis. A case report.
AB  - PURPOSE: To present a case report on a patient with keratouveitis after exposure
      to a tarantula. MATERIAL: A 15-year-old boy presented with ocular redness and
      discomfort after his pet tarantula (Chilean Rose) had walked over his face.
      METHODS: Clinical examination revealed inflammatory reactions in the corneas and
      the anterior chamber. After nine months, two subepithelial infiltrates of the
      cornea emerged, surrounding tarantula hairs of the stroma. The hairs were
      removed. RESULTS: Topical steroids relieved the symptoms, but ten months after
      exposure there was still a mild reaction in the anterior chamber of the right
      eye. CONCLUSION: Hairs from pet tarantulas might penetrate deeply into the eye
      and give keratouveitis. The hairs might be difficult to detect. Though rare, this
      phenomenon should be known by both ophthalmologists and the public.

PMID- 11594996
TI  - Putative non-uniting double central retinal artery system.
AB  - PURPOSE: To report a case of probable non-uniting double retinal arterial
      circulation. METHODS: Case report. A 66-year-old man suffered central retinal
      artery occlusion. RESULTS: The medical findings and angiographic workup supported
      the existence of double central retinal circulation not uniting before entering
      the globe and independently branching in the retina. CONCLUSIONS: In previously
      recognized unusual anatomic structures of the central retinal artery two parallel
      arteries were recognized, both of which united before entering the globe. We have
      described a rare anatomic variant in which those arteries remained separated
      after entering the globe, including while branching in the retina.

PMID- 11594995
TI  - Planned two-step vitrectomy for extremely large and thick subretinal hematoma.
AB  - PURPOSE: To describe a new surgical strategy, planned two-step vitrectomy, for a
      large and thick subretinal hematoma involving 3 or more quadrants of the fundus.
      SURGICAL METHODS: In a first-step vitrectomy, a retinotomy was made in the
      posterior pole, after any vitreous hemorrhage had been removed. Following fluid
      gas exchange with no laser photocoagulation around the retinotomy, patients took
      a face-down position for a few days to a week to facilitate subretinal hemorrhage
      movement to the vitreous cavity and anterior chamber. In a second-step surgery,
      the hemorrhage in the vitreous cavity and anterior chamber was washed out. The
      remaining subretinal hemorrhage was aspirated, and the retina was reattached with
      fluid-gas exchange and laser photocoagulation around the retinotomy. RESULTS: The
      planned two-step vitrectomy was performed in 4 consecutive patients with large
      and thick subretinal hematomas involving 3 or more quadrants seen during a 3-year
      period. By a face-down position after the first-step vitrectomy, subretinal
      hemorrhage moved to the vitreous cavity and anterior chamber. The remaining
      subretinal hemorrhage in a smaller quantity could be easily removed, leading to
      retinal reattachment in the second-step surgery. CONCLUSIONS: The planned two
      step vitrectomy is a safer and more effective procedure for removing a large
      quantity of subretinal hemorrhage in a shorter period of surgical time, compared
      with hemorrhage removal in a single vitrectomy.

PMID- 11594997
TI  - Scedosporium apiospermum chorioretinitis.
AB  - PURPOSE: A case of a 24-year-old immunocompetent woman who developed unilateral
      Scedosporium apiospermum chorioretinitis and diffuse cervical lymphadenitis 10
      years after facial steroid injection is described. METHODS: The patient was
      initially treated for the misdiagnosis of tuberculous lymphadenitis.
      Contemporaneous to the enlargement of her lymph nodes, she experienced gradual
      loss of vision in her left eye. She subsequently underwent lymph node biopsy.
      RESULTS: Histopathologic sections stained with Grocott's methenamine silver
      showed branched septate hyphae and cultures on Sabouraud's agar yielded
      Scedosporium apiospermum. The patient received oral itraconazole 200 mg twice
      daily. Lymphadenitis regressed within a year and chorioretinitis scarred within
      two years. CONCLUSION: Scedosporium apiospermum may cause isolated
      chorioretinitis in an immunocompetent individual years after local surgery or
      trauma and result in significant visual morbidity. Treatment may require
      prolonged use of systemic itraconazole.

PMID- 11594998
TI  - Corona phenomenon as visual aura symptom in migraine.
AB  - The visual illusion of a typical corona phenomenon was represented as a visual
      migraine aura symptom in six of 562 Migraine Art pictures, whereas another five
      pictures illustrated atypical variants of the said illusion. The extra edges of
      the corona phenomenon are commonly seen around the perceptual images of objects,
      but in atypical cases they can similarly surround illusory images and both
      elementary and complex hallucinatory images. The corona phenomenon is strongly
      associated with visual loss and the presence of elementary geometric
      hallucinations.

PMID- 11594999
TI  - Self-administered pain-relieving manoeuvres in primary headaches.
AB  - We investigated the use of self-administered pain-relieving manoeuvres on a
      sample of 400 patients with primary headaches--represented by an even
      distribution of migraine without aura (MO), migraine with aura (MA), episodic
      tension-type headache (TH), and cluster headache (CH)--consecutively seen at
      Padua and Parma Headache Centres. Manoeuvres on various regions of the head were
      used by 258 patients (65% of the cases). The most applied procedures were:
      compression (114 out of 382 manoeuvres; 30%), application of cold (27%), massage
      (25%) and application of heat (8%). A significant (P < 0.001) relationship was
      found between headache diagnoses and type of manoeuvre. In MO patients the
      application of cold (38% of the manoeuvres) and compression (36%), used mainly on
      the forehead and temples, prevailed; compression, mainly on the temples, was the
      most frequent procedure (44%) in MA patients. Massage on the temples and nape was
      the predominant manoeuvre (43%) in TH patients, whereas in the CH group, which
      more often required heterogeneous procedures, none of the above-mentioned
      manoeuvres was prevalent. Compression, as a diagnostic criterion for MO, had a
      sensitivity of 33% and a specificity of 86%; for the application of cold the
      figures were 36% and 84%, respectively. Massage had a sensitivity of 33% and a
      specificity of 80% for TH. The efficacy of the self-administered manoeuvres in
      reducing pain was scarce. Only 8% of the manoeuvres, in fact, resulted in a good
      or excellent pain control. Moreover, the efficacy of the manoeuvre was often
      momentary, wearing off when the manoeuvre stopped. In spite of this, 46% of the
      subjects used the manoeuvres constantly, at each attack.

PMID- 11595000
TI  - Safety and efficacy of PNU-142633, a selective 5-HT1D agonist, in patients with
      acute migraine.
AB  - In this randomized, double-blind, placebo-controlled, parallel-group study,
      patients received a single 50-mg oral dose of a 5-HT(1D) agonist, PNU-142633 (n =
      34), or matching placebo (n = 35) during an acute migraine attack. No
      statistically significant treatment effects were observed at 1 and 2 h after
      dosing, even after stratifying by baseline headache intensity. At 1 and 2 h post
      dose, 8.8% and 29.4% of the PNU-142633 group, respectively, and 8.6% and 40.0% of
      the placebo group, respectively, experienced headache relief; 2.9% and 8.8% of
      the PNU-142633 group and 0% and 5.7% of the placebo group were free of headache
      pain. Adverse events associated with PNU-142633 treatment included chest pain
      (two patients) and QTc prolongation (three patients). Results from this study
      suggest that anti-migraine efficacy is not mediated solely through the 5-HT(1D)
      receptor subtype, although this receptor may contribute, at least in part, to the
      adverse cardiovascular effects observed with 5-HT agonist medications.

PMID- 11595001
TI  - Consulting behaviour in migraine and tension-type headache sufferers: a
      population survey in Santiago, Chile.
AB  - Migraine and tension-type headaches are the most frequent types of headaches in
      Santiago. The purpose of this paper is to describe the patterns of health care
      utilization in migraine and compare them with tension-type headache sufferers in
      a community-based study of the prevalence of headache in Santiago, Chile. A two
      step questionnaire was administered to an age- and gender-representative sample
      of 1540 eligible subjects who were aged 15 years or older. Of these, 1385 (89.9%)
      responded. Cases were defined according to the most frequent type of headache
      experienced in the last year. Migraine and tension-type headaches were diagnosed
      according to a questionnaire-based algorithm constructed using the IHS criteria.
      Consultation rates in migraneurs were significantly (P < 0.01) higher (63%) than
      in tension-type headache suffers (39%). Migraneurs were more likely to be female,
      younger and less educated, and had more severe attacks than those with tension
      type headache. Female sex, younger age, fewer years of education in migraneurs
      and younger age and moderate or severe headache in tension-type headache
      sufferers were found to be independently associated with the likelihood of ever
      consulting, respectively. Migraneurs are more likely to consult than tension-type
      headache suffers in this population.

PMID- 11595002
TI  - The importance of sex, age, needle size, height and body mass index in post
      lumbar puncture headache.
AB  - In this prospective study 37% of 239 patients developed a post-lumbar puncture
      headache (PPH) after a diagnostic lumbar puncture. PPH was more prevalent in
      females than males (46% vs. 21%; P = 0.0003) as were the severest form of PPH
      (64% vs. 23%; P = 0.02) and nausea (74% vs. 39%; P = 0.01) in those who developed
      PPH. Females scored their pain in the upright position more severe on a 100-mm
      visual analogue scale than males (median 60 mm vs. 47.5 mm; P = 0.02). The
      frequency of PPH was higher with the use of a 20-gauge compared with a 22-gauge
      needle in all patients (50% vs. 26%; P = 0.0002) and in females (57% vs. 36%; P =
      0.02) and males (38% vs. 10%; P = 0.004), separately. Neither age, weight,
      height, nor body mass index (BMI), influenced the prevalence of PPH, but tinnitus
      was more prevalent in tall compared with smaller patients (53% vs. 17%; P =
      0.02). Old age was associated with a long median pain delay upon rising, and
      also, small patients tended to report a longer median pain delay than tall
      patients. The pain intensity changed more slowly upon rising and reclining in
      patients with a high BMI than in those with a lower BMI (median 60 s vs. 12 s; P
      = 0.02). The results concerning height, BMI and needle size might be anticipated
      according to the leakage theory. In a multivariate analysis sex (P = 0.0003) and
      needle size (P = 0.0002) were related to the development of PPH on a
      statistically significant level. Furthermore, the pain severity was positively
      related to female sex (P = 0.03) and young age (P = 0.03). The pain delay
      increased with age (P = 0.008) and the pain decrease time increased with an
      increasing BMI (P = 0.04).

PMID- 11595004
TI  - Milestones in headache research. A tribute to Jes Olesen.

PMID- 11595003
TI  - Drug-resistant cluster headache responding to gabapentin: a pilot study.
AB  - Prompted by the results of gabaergic drugs, such as valproate and topiramate, we
      performed this pilot study to assess the effect of gabapentin in cluster
      headache. Eight patients suffering from episodic cluster headache and four
      suffering from chronic cluster headache were studied. All of them had failed to
      respond to traditional prophylactic drugs. The design of the study was an open
      trial. The main parameter for effectiveness was the number of daily attacks.
      Gabapentin was given at the daily dosage of 900 mg. All patients were pain free
      after a maximum of 8 days after starting therapy, with a bout duration thus
      reduced to 16-40% of the average previous bouts (only applies to episodic cluster
      patients). We hypothesize that the gabaergic action of gabapentin, perhaps
      combined with other mechanisms, such as calcium channel blockade, may be
      responsible for its remarkable effects on cluster headache.

PMID- 11595005
TI  - History of headache research in Denmark.
AB  - Headache research in Denmark started with the description in 1949 by Dalsgaard
      Nielsen of the percutaneous nitroglycerin test. In 1976 Jes Olesen started The
      Copenhagen Acute Headache Clinic and from that time modern headache research
      began in Denmark. Specific changes in regional cerebral blood flow during attacks
      of migraine with aura, spreading oligaemia, were described for the first time in
      1980. The first headache classification with operational diagnostic criteria was
      published in 1988 and used in a Danish population study from 1989. The lifetime
      prevalence of migraine was 8% in men and 25% in women. An intravenous
      nitroglycerin test was introduced in 1989 and has been developed as an
      experimental headache model. In 1993 it was suggested by Jes Olesen et al. that
      NO supersensitivity could be a possible molecular mechanism of migraine pain.
      Recent genetic studies have supported the distinction between migraine with aura
      and migraine without aura. From the middle of the 1980s the pathophysiology of
      tension-type headache has been investigated and recent results indicate central
      sensitization in patients with chronic tension-type headache.

PMID- 11595006
TI  - Global impact of Danish headache research.
AB  - Over the past 40 years, Denmark has established a world reputation for the
      comprehensive nature and excellence of its headache research. Advances have been
      made in epidemiology, genetics, pathophysiology and treatment across the whole
      spectrum of headache entities. Moreover, the IHS classification of headache, the
      guidelines for clinical trials and text books on the basic mechanisms and
      management of headaches were initiated from Denmark. These achievements are a
      tribute to all those who have participated and to the continuing leadership of
      Jes Olesen.

PMID- 11595007
TI  - Cortical spreading depression in migraine.
AB  - Cortical spreading depression (CSD) is associated with a dramatic failure of
      brain ion homeostasis as well as efflux of excitatory amino acids from nerve
      cells and increased energy metabolism. There is strong clinical and experimental
      evidence to suggest that CSD is involved in the mechanism of migraine. This paper
      will, based on the experience related to the detection of CSD in humans, discuss
      pitfalls and possible strategies for detection of CSD in man. Development of
      reliable methods for detection of CSD in humans will determine the extent to
      which the large body of experimental findings from animal studies of CSD can be
      applied to the investigation and treatment of human brain disease. The paper is
      based on the experience that has been gained from two decades of studies of CSD
      in relation to clinical neurological diseases.

PMID- 11595008
TI  - Sensory nerves in man and their role in primary headaches.
AB  - The sensory innervation of intracranial vessels originate in the trigeminal
      ganglion and comprise the following signal substances; calcitonin gene-related
      peptide (CGRP), substance P, neurokinin A, pituitary adenylate cyclase activating
      peptide (PACAP) and nitric oxide (NO). Studies in patients have revealed a clear
      association between head pain and the release of CGRP. In cluster headache and in
      a case of chronic paroxysmal headache there is in addition release of vasoactive
      intestinal peptide (VIP), which was associated with the facial symptoms (nasal
      congestion, rhinorrhea). In parallel with triptan administration, acting via 5
      HT(1B/1D) receptors, head pain subside and neuropeptide release normalise. These
      data show the involvement of sensory and parasympathetic mechanisms in the
      pathophysiology of primary headaches.

PMID- 11595009
TI  - Recent advances in pain research: implications for chronic headache.
AB  - Within the last 2 decades there has been an explosion in new information on
      mechanisms underlying pain. Unfortunately this information has not resulted in a
      similar improvement of our handling of patients with chronic pain including
      chronic musculoskeletal pain. Neuronal hyperexcitability, which apparently is a
      key phenomenon in many (if not all) types of chronic pain results in changes in
      the nervous system from the level of the peripheral nociceptor to the highest
      cortical centers in the brain. The neuronal plastic changes in chronic pain
      conditions makes the nociceptive system amenable for treatment with several
      traditional as well as nontraditional types of interventions. Two treatment areas
      that seem worth exploring within chronic pain including headache concerns
      preventive measures and endogenous pain modulation.

PMID- 11595010
TI  - Classification of headaches.
AB  - It was not until 1962 that the Ad-Hoc Committee of the National Institute of
      Health first published a classification of headache syndromes by brief glossary
      definitions. The general disadvantage of such glossary definitions is that they
      require subjective interpretation. Therefore under the chairmanship of Prof. Jes
      Olesen, Copenhagen, the International Headache Society published in 1988 on the
      basis of empirical findings a first ever headache classification using
      operationalized criteria. The headache classification of the International
      Headache Society was immediately translated into the world's major languages and
      was adopted by all national headache societies represented in the International
      Headache Society, the World Health Organisation and the World Federation of
      Neurology. The new classification proved so successful and enjoyed such rapid
      international acceptance that no revision was undertaken until 1999. The second
      edition, again under the chairmanship of Prof. Jes Olesen, will probably be
      completed in 2002. The classification produced such a high degree of inspiration
      and motivation of pathophysiological and epidemiological research work that
      knowledge in the field of headache has displayed growth unparalleled in any other
      field of neurological research. This development was made possible by the
      determined work of the Chairman of the Headache Classification Committee, Prof.
      Jes Olesen. He succeeded in bringing together international researchers,
      motivating them and jointly turning the current fund of knowledge into a evidence
      based classification. Prof. Jes Olesen thus performed the decisive pioneering
      work for all those who have to do with headaches-patients, doctors and
      scientists. The IHS classification is the most frequently cited text and one of
      the most important milestones in the history of the scientific study of
      headaches.

PMID- 11595011
TI  - Epidemiology of headache.
AB  - Headache disorders constitute a public-health problem of enormous proportions,
      with an impact on both the individual sufferer and society. Epidemiological
      knowledge is required to quantitate the significance of these disorders. The
      effects on individuals can be assessed by examining prevalence, distribution,
      attack frequency and duration, and headache-related disability. The socio
      economic burden includes both direct costs associated with health care
      utilization and costs associated with missed work due to sickness absence or
      reduced efficiency. The individual and socio-economic burden of headaches is
      substantial. Headache disorders deserve more attention, especially concerning
      strategies leading to adequate primary prevention, diagnosis and treatment.

PMID- 11595012
TI  - Genetics of migraine without aura, migraine with aura, migrainous disorder, head
      trauma migraine without aura and tension-type headache.
AB  - This review is a tribute to Professor Jes Olesen involvement in the genetics of
      migraine and tension-type headache as it is coming up to his 60th birthday.

PMID- 11595013
TI  - Human migraine models.
AB  - The need for experimental models is obvious. In animal models it is possible to
      study vascular responses, neurogenic inflammation, c-fos expression etc. However,
      the pathophysiology of migraine remains unsolved, why results from animal studies
      not directly can be related to the migraine attack, which is a human experience.
      A set-up for investigations of experimental headache and migraine in humans, has
      been evaluated and headache mechanisms explored by using nitroglycerin and other
      headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated
      cascade seems to be responsible for the induced headache and migraine.
      Perspectives are discussed.

PMID- 11595014
TI  - Mechanisms of tension-type headache.
AB  - Despite tension-type headache represents one of the most frequent and costly
      diseases in modern society only very little research on this disease has actually
      been carried out. In contrast to former belief tension-type headache is a
      separate entity that can and should be separated from migraine. No specific
      biochemical abnormalities have yet been identified but a reliable human model of
      tension-type headache has been developed by means of infusion of a NO-donor,
      glyceryl trinitrate. Myofascial factors and peripheral sensitization of
      nociceptors play an important role in the episodic form, and central
      sensitization has been demonstrated in the chronic form. As chronic tension-type
      headache usually evolves from the episodic form, prevention and reversal of this
      central sensitization may be an important target for future pathophysiological
      studies and drug development.

PMID- 11595015
TI  - Distal limb malformations: underlying mechanisms and clinical associations.
AB  - Congenital malformations of the extremities are conspicuous and have been
      described through the ages. Over the past decade, a wealth of knowledge has been
      generated regarding the genetic regulation of limb development and the underlying
      molecular mechanisms. Recent studies have identified several of the signaling
      molecules, growth factors, and transcriptional regulators involved in the
      initiation and maintenance of the apical ectodermal ridge (AER) as well as the
      molecular markers defining the three axes of the developing limb. Studies of
      abnormal murine phenotypes have uncovered the role played by genes such as p63
      and Dactylin in the maintenance of AER activity. These phenotypes resemble human
      malformations and in this review we describe the underlying mechanisms and
      clinical associations of split hand/foot malformation and ectrodactyly-ectodermal
      dysplasia-cleft lip/palate syndrome, which have both been associated with
      mutations in the p63 gene.

PMID- 11595017
TI  - Identification of a Crohn's disease susceptibility gene.

PMID- 11595018
TI  - Two new genes have been identified for the obesity disorder Bardet-Biedl
      syndrome.

PMID- 11595019
TI  - Family-based transmission disequilibrium test (TDT) and case-control association
      studies reveal surfactant protein A (SP-A) susceptibility alleles for respiratory
      distress syndrome (RDS) and possible race differences.
AB  - A key cause of respiratory distress syndrome (RDS) in the prematurely born infant
      is deficiency of pulmonary surfactant, a lipoprotein complex. Both low levels of
      surfactant protein A (SP-A) and SP-A alleles have been associated with RDS. Using
      the candidate gene approach, we performed family-based linkage studies to discern
      linkage of SP-A to RDS and identify SP-A susceptibility or protective alleles.
      Moreover, we performed case-control studies of whites and blacks to detect
      association between RDS and SP-A alleles. Transmission disequilibrium test (TDT)
      analysis revealed that the frequency of transmission (from parent to the
      offspring with RDS) of alleles 6A(2) and 1A(0) and of 1A(0)/6A(2) haplotype in
      RDS was increased, whereas transmission of alleles 1A(5) and 6A(4) and of
      haplotype 1A(5)/6A(4) was decreased. Extended TDT analysis further strengthened
      the observations made. The case-control studies showed that in whites or blacks
      with RDS the frequencies of specific genotypes, 1A(0) and 6A(2) or 1A(0), were
      increased, respectively, but the frequency of specific 6A(3) genotypes was
      increased in certain white subgroups and decreased in blacks. Regression analysis
      revealed gestational age (GA) and 6A(3) genotypes are significant factors in
      blacks with RDS. In whites with RDS, GA and antenatal steroids are important
      factors. The data together indicate linkage between SP-A and RDS; certain SP-A
      alleles/haplotypes are susceptibility (1A(0), 6A(2), 1A(0)/6A(2)) or protective
      (1A(5), 6A(4), 1A(5)/6A(4)) factors for RDS. Some differences between blacks and
      whites with regard to SP-A alleles may exist.

PMID- 11595020
TI  - Lipoprotein(a) as a risk factor for maternal cardiovascular disease mortality in
      kindreds with familial combined hyperlipidemia or familial hypertriglyceridemia.
AB  - Most but not all epidemiologic studies have shown that lipoprotein(a) [Lp(a)] is
      a risk factor for cardiovascular disease (CVD). Lp(a) levels are also strongly
      genetically influenced. The purpose of this study was to evaluate the association
      between Lp(a) levels in adult offspring and parental CVD mortality in 61 kindreds
      with familial forms of hyperlipidemia. The study sample consisted of offspring
      parent pairs in which offspring had fasting Lp(a) measurements and parents had 20
      year vital status data and standardized cause-of-death classification if
      deceased. Linear regression analyses, using a robust variance estimator, were
      performed separately for 241 offspring with known maternal history (114 mothers)
      and 194 offspring with known paternal history (93 fathers). Maternal history of
      CVD mortality was significantly (p=0.004) associated with 2.4-fold higher median
      Lp(a) levels in offspring compared with those with no maternal history,
      independent of diabetes, lipid-lowering medications and hormone use. No
      association was observed between paternal CVD mortality and offspring Lp(a)
      levels (p=0.505). Adjusting for apolipoprotein(a) kringle 4 number did not alter
      these parent-specific associations. In conclusion, Lp(a) levels in offspring may
      be associated with maternal but not paternal history of CVD mortality. This
      parent-specific finding needs to be confirmed in other samples of high-risk
      families.

PMID- 11595021
TI  - High incidence rate and absent family histories in one quarter of patients newly
      diagnosed with Huntington disease in British Columbia.
AB  - The advent of the direct mutation test for Huntington disease (HD) has made it
      possible to identify a previously unrecognized symptomatic population of HD,
      including those with an atypical presentation or patients without a family
      history of HD. The present study investigated the uptake of this test in the
      province of British Columbia (BC), Canada and assessed the incidence rate and
      rate of identification of new mutations for HD. All symptomatic individuals
      residing in BC who were referred for the genetic test for HD between 1993 and
      2000 (n=205) were analyzed for CAG expansion, baseline demographics and clinical
      data, and a family history of HD. A total of 141 (or 68.8%) had a CAG expansion >
      or =36. Of these, almost one-quarter (24.1%) did not have a family history of HD.
      An extensive chart review revealed that 11 patients (or 7.8%) had reliable
      information on both parents (who lived well into old age) and therefore possibly
      could represent new mutations for HD. This indicates a three to four times higher
      new mutation rate than previously reported. Our findings also show that the
      yearly incidence rate for HD was 6.9 per million, which is two times higher than
      previous incidence studies performed prior to the identification of the HD
      mutation. We also identified five persons with a clinical presentation of HD but
      without CAG expansion (genocopies) (2.4%).

PMID- 11595022
TI  - Trisomy rescue by postzygotic unbalanced (X;14) translocation in a girl with
      dysmorphic features.
AB  - In this report we present the clinical features and molecular and cytogenetic
      findings in a female with partial trisomy 14q. Molecular and cytogenetic studies
      allowed us to determine that the extra 14q material (of paternal origin) was
      translocated postzygotically onto the maternal X chromosome. Consequently, only
      the derivative X chromosome was inactivated, although inactivation apparently did
      not spread over the entire chromosome 14q. This partial inactivation makes the
      present case unusual, giving rise to phenotypic features absent in other patients
      with partial trisomy 14q, typically restricted to the distal part of the
      chromosome.

PMID- 11595023
TI  - Comparative genomic hybridisation in mentally retarded patients with dysmorphic
      features and a normal karyotype.
AB  - Segmental aneusomy for small chromosomal regions has been shown to be a common
      cause of mental retardation and multiple congenital anomalies. A screening method
      for such chromosome aberrations that are not detected using standard cytogenetic
      techniques is needed. Recent studies have focused on detection of subtle terminal
      chromosome aberrations using subtelomeric probes. This approach however excludes
      significant regions of the genome where submicroscopic rearrangements are also
      liable to occur. The aim of the present study was to evaluate the efficiency of
      comparative genomic hybridisation (CGH) for screening of submicroscopic
      chromosomal rearrangements. CGH was performed in a cohort of 17 patients (14
      families) with mental retardation, dysmorphic features and a normal karyotype.
      Five subtle unbalanced rearrangements were identified in 7 patients. Subsequent
      FISH studies confirmed these results. Although no interstitial submicroscopic
      rearrangement was detected in this small series, the study emphasises the value
      of CGH as a screening approach to detect subtle chromosome rearrangements in
      mentally retarded patients with dysmorphic features and a normal karyotype.

PMID- 11595024
TI  - Association of a single nucleotide polymorphism in the TIGR/MYOCILIN gene
      promoter with the severity of primary open-angle glaucoma.
AB  - Primary open-angle glaucoma (POAG) is a highly prevalent optic neuropathy and a
      major cause of irreversible blindness, with elevation of intraocular pressure
      (IOP) being a primary risk factor. The trabecular meshwork-inducible
      glucocorticoid response (TIGR)/MYOCILIN (MYOC) gene coding region is mutated in 3
      4% of POAG patients. Here, in a retrospective study of 142 POAG patients, we
      evaluated the influence on glaucoma phenotype of a novel biallelic polymorphism (
      1000C/G) located in the upstream region of the MYOC gene. Allele frequencies were
      similar among patients and controls. However, the G allele (frequency 17.6%),
      also designated as MYOC.mt1, was associated with an increased IOP (+4.9 mmHg,
      p=0.0004) and a more damaged visual field (p=0.02). Both effects were predominant
      in females. Moreover, whereas IOP in MYOC.mt1 noncarriers decreased very markedly
      to the normal range between diagnosis and inclusion in the study (p=3 x 10(-5) in
      both males and females), reflecting successful therapy, it decreased less
      noticeably in MYOC.mt1+ male patients (p=0.005) and not at all in MYOC.mt1+
      female patients. MYOC.mt1 appears therefore to be an indicator of poor IOP
      control and greater visual field damage in diagnosed POAG patients, potentially
      due to a lack of response to therapeutic intervention. Its typing might help in
      the selection of treatment paradigms for the management of POAG patients.

PMID- 11595025
TI  - Comparative analysis of isodisomic and heterodisomic segments in cases with
      maternal uniparental disomy 14 suggests more than one imprinted region.
AB  - The results of molecular investigations of 21 cases with complete or segmental
      maternal uniparental disomy (UPD) 14 published in the literature were compared
      with respect to isodisomic and heterodisomic segments. The aim of the study was
      to find hints toward imprinted regions other than the recently defined imprinted
      segment 14q32. Three regions with no isodisomic molecular marker were found. The
      most distal of these regions located on 14q32.12 and 14q32.13 supports the
      hypothesis of genomic imprinting as the cause of the maternal UPD 14 phenotype by
      synteny to the maternally imprinted region on mouse distal chromosome 12 and
      correlation with the recently defined imprinting cluster on human chromosome
      14q32. The other two heterodisomic areas located on 14q11.2-->14q12 and 14q21.1-
      >14q31.2 are hints toward one or more additional regions of genomic imprinting on
      human chromosome 14.

PMID- 11595026
TI  - Medical genetics and patient use of the Internet.
AB  - Clinical experience suggests that the Internet is increasingly becoming a
      resource for patients seen in medical genetics. A prospective analysis was
      performed exploring patient use of the Internet prior to attending a medical
      genetics appointment. We administered 200 questionnaires assessing: 1) the
      frequency of patient use of the Internet for genetic information, 2) factors
      associated with Internet use, 3) patient assessment of the value of the
      information, and 4) patient views of the responsibility of medical genetics
      professionals to be familiar with Internet information. Results show that 77%
      (153/200) of patients have access to the Internet of which 29% (44/153) report
      searching the Internet for genetic information. A correlation was found between
      patient use of the Internet and reason for referral (p<0.001), presence of a
      specific diagnosis (p<0.001), and frequency of Internet use (p<0.05). Overall,
      80% (33/41) of patients found Internet information useful. Seventy-four percent
      (115/155) believed that medical genetics professionals have a responsibility to
      review relevant Internet sites for accuracy and 80% (123/153) felt that
      professionals should provide their patients with appropriate and useful Internet
      sites. These results suggest that the role of medical genetics professionals is
      changing as a result of the development of the Internet.

PMID- 11595027
TI  - Features within the holoprosencephaly spectrum in sibs with a Robertsonian
      (14q;22q) translocation chromosome.

PMID- 11595028
TI  - Hypermobility type of Ehlers-Danlos syndrome: influence of pregnancies.

PMID- 11595029
TI  - Homeostatic plasticity induced by chronic block of AMPA/kainate receptors
      modulates the generation of rhythmic bursting in rat spinal cord organotypic
      cultures.
AB  - Generation of spontaneous rhythmic activity is a distinct feature of developing
      spinal networks. We report that rat embryo organotypic spinal cultures contain
      the basic circuits responsible for pattern generation. In this preparation
      rhythmic activity can be recorded from ventral interneurons and is
      developmentally regulated. When chronically grown in the presence of an
      AMPA/kainate receptor blocker, this circuit expresses long-term plasticity
      consisting largely of increased frequency of fast synaptic activity and reduction
      in slow GABAergic events. We examined whether, once this form of homeostatic
      plasticity is established, the network could still exhibit rhythmicity with
      properties similar to controls. Control or chronically treated ventral
      interneurons spontaneously generated (with similar probability) irregular,
      network-driven bursts over a background of ongoing synaptic activity. In control
      cultures increasing network excitability by strychnine plus bicuculline, or by
      raising [K(+)](o), induced rapid-onset, regular rhythmic bursts. In treated
      cultures the same pharmacological block of Cl(-)-mediated transmission or high
      K(+) application also induced regular patterned activity, although significantly
      faster and, in the case of high K(+), characterized by slow onset due to
      postsynaptic current summation. Enhancing GABAergic transmission by pentobarbital
      surprisingly accelerated the high-K(+) rhythm of control cells (though depressing
      background activity), whereas it slowed it down in chronically treated cells.
      This contrasting effect of pentobarbital suggests that, to preserve bursting
      ability, chronic slices developed a distinct GABAergic inhibitory control on over
      expressed bursting circuits. Conversely, in control slices GABAergic transmission
      depressed spontaneous activity but it facilitated bursting frequency. Thus, even
      after homeostatic rearrangement, developing mammalian spinal networks still
      generate rhythmic activity.

PMID- 11595030
TI  - Independent receptors for diadenosine pentaphosphate and ATP in rat midbrain
      single synaptic terminals.
AB  - Diadenosine pentaphosphate (Ap5A) and adenosine 5'-triphosphate (ATP) stimulate a
      intrasynaptosomal calcium concentration [Ca(2+)](i) increase via specific
      purinergic receptors in rat midbrain synaptosomes, although nothing is known
      about their distribution in presynaptic terminals. A microfluorimetric technique
      to measure [Ca(2+)](i) increase using the dye FURA-2AM, has permitted study of
      the presence of dinucleotide and P2X receptors in independent isolated synaptic
      terminals. Our results demonstrate the existence of three populations of
      synaptosomes: one with dinucleotide receptors (12%), another with P2X receptors
      (20%) and a third with both (14%). It has been possible to demonstrate that the
      activation of these receptors occurs only in the presence of extracellular Ca(2+)
      and that it is also coupled with voltage-dependent Ca(2+) channels. Finally 54%
      of the synaptosomes that responded to K(+) did not present any calcium increase
      mediated by the nucleotides used. In summary, ATP and dinucleotides exhibit
      specific ionotropic receptors that can coexist or not on the same synaptic
      terminal.

PMID- 11595031
TI  - ATP stimulation of P2X(7) receptors activates three different ionic conductances
      on cultured mouse Schwann cells.
AB  - Extracellular ATP, by acting on P2 purinergic receptors, is a potent mediator of
      cell-to-cell communication both within and between the nervous and the immune
      systems. We show here by patch-clamp recording, fluorescent dye uptake and
      immunocytochemistry that, in cultured mouse Schwann cells, ATP activates a P2X(7)
      receptor associated with three different ionic conductances. In control
      conditions, ATP activated an inward current (I(ATP)) with a low potency (EC(50),
      7.2 mM). Replacing ATP either by the ATP analogue 2',3'-O-(4-benzoyl-4-benzoyl)
      ATP (BzATP) or by the tetraacidic form ATP(4-) potentiated the inward current
      (ATP(4-) EC(50), 375 microM). ATP and BzATP currents were strongly reduced by
      periodate oxidized ATP (oATP), an antagonist of P2X(7) receptors. IATP was a
      mixed current composed of a nonselective cationic conductance, a cationic
      conductance selective for K(+) and an anionic conductance selective for Cl(-).
      The activation of the K(+) conductance was dependent on an influx of Ca(2+), and
      was blocked by charybdotoxin (ChTX) and tetraethylammonium (TEA), two potent
      antagonists of large conductance Ca(2+)-activated K(+) channels (BK channels).
      The activation of the Cl(-) conductance was insensitive to Ca(2+) but required
      the presence of K(+). Total removal of K(+) blocked both the Ca(2+)-activated
      K(+) conductance and the Cl(-) conductance, unveiling the P2X(7) nonselective
      cationic conductance. The P2X(7) receptor was localized by immunocytochemistry
      using a polyclonal antibody, anti-P2X(7), whilst its expression and functionality
      were both detected by the uptake of Lucifer Yellow. This receptor could regulate
      the synthesis and the release of cytokines by Schwann cells during
      pathophysiological events.

PMID- 11595032
TI  - Caspase inhibitors increase short-term survival of progenitor-cell progeny in the
      adult rat dentate gyrus following status epilepticus.
AB  - The dentate gyrus (DG) is one of the few regions in the brain that continues to
      produce new neurons throughout adulthood. Seizures not only increase
      neurogenesis, but also lead to death of DG neurons. We investigated the
      relationship between cell death and neurogenesis following seizures in the DG of
      adult rats by blocking caspases, which are key components of apoptotic cell
      death. Multiple intracerebroventricular infusions of caspase inhibitors
      (pancaspase inhibitor zVADfmk, and caspase 3 and 9 inhibitor) prior to, just
      after, 1 day after, and 1 week following 2 h of lithium-pilocarpine-induced
      status epilepticus reduced the number of terminal deoxynucleotidyl transferase
      mediated fluorescein-dUTP nick-end labelled (TUNEL) cells and increased the
      number of bromodeoxyuridine (BrdU) -stained proliferated cells in the subgranular
      zone at 1 week. The caspase inhibitor-treated group did not differ from control
      at 2 days or 5 weeks following the epileptic insult. Our findings suggest that
      caspases modulate seizure-induced neurogenesis in the DG, probably by regulating
      apoptosis of newly born neurons, and that this action can be suppressed
      transiently by caspase inhibitors. Furthermore, although previous studies have
      indicated that increased neuronal death can trigger neurogenesis, we show here
      that reduction in apoptotic death may be associated with increased neurogenesis.

PMID- 11595033
TI  - Immobilized amyloid precursor protein constructs: a tool for the in vitro
      screening of glial cell reactivity.
AB  - Astrocytes and microglia are closely associated with amyloid plaques in
      Alzheimer's disease (AD). Microglia constitute the first barrier surrounding
      plaques, although they seem to be unable to remove them efficiently. We evaluated
      the reaction of microglial cells from neonatal rats and mice to plaque mimetics.
      The C-terminal part of the amyloid precursor protein (APP) or amyloid peptide (A
      beta) was immobilized to either 60-microm or 2.8-microm beads and incubated with
      microglial cells. Beads of 60 microm, having approximately the size of senile
      plaques, were not phagocytosed, in contrast to 2.8-microm beads, which were
      phagocytosed by microglia but not by astrocytes. Once taken up by the cells,
      proteins immobilized to the beads were degraded rapidly, as confirmed by mass
      spectrometry and immunofluorescence with an antibody against beta-amyloid. On the
      other hand, no protein degradation was observed with 60-microm beads. Also,
      probably as a reaction to its incapability to phagocytose the beads, glia
      organized around the beads and started to proliferate. Cell proliferation was
      more pronounced when the beads contained the A beta epitope compared with the
      beads with an inert surface. This in vitro effect could be exploited to set up a
      screening assay for compounds that ameliorate the adverse reaction of microglia
      supposed to contribute to the pathogenesis of AD.

PMID- 11595034
TI  - Effect of vasopressin on the input-output properties of rat facial motoneurons.
AB  - Vasopressin can directly excite facial motoneurons in young rats and mice. It
      acts by generating a persistent inward current, which is Na(+)-dependent,
      tetrodotoxin-insensitive and voltage-gated. This peptide-evoked current is
      unaffected by Ca(++) or K(+) channel blockade and is modulated by extracellular
      divalent cations. In the present work, we determined how vasopressin alters the
      input-output properties of facial motoneurons. Whole-cell recordings were
      obtained from these neurons in the current clamp mode, in brainstem slices of
      young rats. Repetitive firing was evoked by injecting depolarizing current
      pulses. Steady-state frequency-current (f-I) relationships were constructed and
      the effect of vasopressin on these relationships was studied. We found that
      vasopressin caused a parallel shift to the left of the cell steady-state f-I
      relationship. This effect persisted in the presence of blockers of K(+) or Ca(++)
      channels. The peptide effect was distinct from that brought about by Ca(++)
      channel suppression or by apamin, a blocker of the mAHP. These latter
      manipulations resulted in an increase in the slope of the steady-state f-I
      relationship. We conclude that the vasopressin-induced modification of the input
      output properties of facial motoneurons is probably exclusively caused by the
      sodium-dependent, voltage-modulated inward current elicited by the peptide,
      rather than being due to indirect effects of the peptide on Ca(++) channels, K(+)
      channels or Ca(++)-dependent K(+) channels. Computer simulation, based on a
      simple model of facial motoneurons, indicates that the introduction of a
      conductance having the properties of the vasopressin-dependent conductance can
      entirely account for the observed peptide-induced shift of the f-I relationship.

PMID- 11595035
TI  - Evaluation of the tetracycline- and ecdysone-inducible systems for expression of
      neurotransmitter receptors in mammalian cells.
AB  - Establishing a stable cell line that expresses a particular protein of interest
      is often a laborious and time-consuming experience. With constitutive expression
      systems, a gradual loss of the highly expressing clones over a given time span
      and/or a severe counter-selection due to toxicity of the expressed protein for
      the host cell line are major drawbacks. In both cases, inducible expression
      systems offer a valuable alternative. Over the years, many regulated expression
      systems have been developed and evaluated. In the present study, we compare the
      efficiency, the advantages and the drawbacks of a tetracycline- and an ecdysone
      inducible system for expression of the reporter protein chloramphenicol
      acetyltransferase and of different G-protein-coupled serotonin (5-HT) receptors.
      A high level of expression of different 5-HT receptors was obtained with the
      tetracycline-inducible system. In the cell line L929, which stably expresses the
      tetracycline-responsive transactivator, a maximum ligand binding of 20,000 and
      9500 fmol/mg protein was measured for the h5-HT(1B) and h5-ht(1F) receptors,
      respectively. In the HEK293rtTA cell line, levels of 15,700, 3000, and 9100 fmol
      bound ligand/mg protein were obtained for the h5-HT(1B), h5-ht(1F) and h5-HT(4b)
      receptors, respectively. These high expression levels remained stable for several
      months of continuous culture. Although the ecdysone-inducible expression system
      was useful for tightly regulated expression, the levels were far lower than those
      obtained with the tetracycline system (e.g. 640 fmol bound ligand/mg protein for
      the h5-ht(1F) receptor in HEK293EcR).

PMID- 11595036
TI  - Dopamine inhibition of auditory nerve activity in the adult mammalian cochlea.
AB  - Efferent feedback systems provide a means for modulating the input to the central
      nervous system. The lateral olivocochlear efferents modulate auditory nerve
      activity via synapses with afferent dendrites below sensory inner hair cells. We
      examined the effects of dopamine, one of the lateral olivocochlear
      neurotransmitters, by recording compound and single unit activity from the
      auditory nerve in adult guinea pigs. Intracochlear application of dopamine
      reduced the compound action potential (CAP) of the auditory nerve, increased the
      thresholds and decreased the spontaneous and driven discharge rates of the single
      unit fibres without changing their frequency-tuning properties. Surprisingly,
      dopamine antagonists SCH-23390 and eticlopride decreased CAP amplitude as did
      dopamine. In some units, both SCH-23390 and eticlopride increased the basal
      activity of auditory nerve fibres leading to an improvement of threshold
      sensitivity and a decrease of the maximum driven discharge rates to sound. In
      other units, the increase in firing rate was immediately followed by a marked
      reduction to values below predrug rates. Because CAP reflects the summed activity
      of auditory nerve fibres discharging in synchrony, both the decrease in sound
      driven discharge rate and the postexcitatory reduction account for the reduction
      in CAP. Ultrastructural examination of the cochleas perfused with eticlopride
      showed that some of the afferent dendrites were swollen, suggesting that the
      marked reduction in firing rate may reflect early signs of excitotoxicity.
      Results suggest that dopamine may exert a tonic inhibition of the auditory nerve
      activity. Removal of this tonic inhibition results in the development of early
      signs of excitotoxicity.

PMID- 11595037
TI  - Distinct properties and differential beta subunit regulation of two C-terminal
      isoforms of the P/Q-type Ca(2+)-channel alpha(1A) subunit.
AB  - Two C-terminal splice variants (BI-1 and BI-2, now termed Ca(v)2.1a and
      Ca(v)2.1b) of the neuronal voltage-gated P/Q-type Ca(2+) channel alpha(1A) pore
      forming subunit have been cloned (Mori et al., 1991, Nature, 350, 398-402). BI-1
      and BI-2 code for proteins of 2273 and 2424 amino acids, respectively, and differ
      only by their extreme carboxyl-termini sequences. Here, we show that, in Xenopus
      oocytes, the two isoforms direct the expression of channels with different
      properties. Electrophysiological analysis showed that BI-1 and BI-2 have peak
      Ba(2+) currents (I(Ba)) at a potential of +30 and +20 mV, respectively. The
      different C-terminal sequence (amino acids 2229-2273) of BI-1 caused a shift in
      steady-state inactivation by +10 mV and decreased the proportion of fast
      component of current inactivation twofold. Likewise, the biophysical changes in
      I(Ba) caused by coexpression of the beta(4) auxiliary subunit were substantially
      different in BI-1- and BI-2-containing channels in comparison to those induced by
      beta(3). Several of these differences in beta regulation were abolished by
      deleting the carboxyl-terminal splicing region. By creating a series of GST
      fusion proteins, we identified two locations in the C-terminal (Leu2090-Gly2229
      for BI-1 and BI-2, and Arg2230-Pro2424 for BI-2 only) that determine the
      differential interaction of beta(4) with the distinct alpha(1A) isoforms. These
      interactions appear to favour the binding of beta(4) to the AID site, and also
      the plasma membrane expression of BI-2. These results demonstrate that the final
      segment of the C-terminal affects alpha(1A) channel gating, interaction and
      regulation with/by the beta subunits. The data will have several implications for
      the understanding of the biophysical effects of many channelopathies in which the
      carboxyl-termini of alpha(1A) and beta(4) are affected.

PMID- 11595038
TI  - Molecular cloning and dendritic localization of rat SH3P7.
AB  - SH3P7 was originally isolated by cloning SH3 domain ligand targets from a mouse
      embryo cDNA library. SH3P7 is an actin-binding protein implicated in antigen
      reception, JNK1 signalling, and Rac activation. It contains a drebrin homology
      sequence in its N-terminal region and a cortactin homology sequence (SH3 domain)
      in its C-terminal region. Both drebrin and cortactin are actin-binding proteins,
      and both have been suggested as possible regulators of the actin cytoskeleton in
      neurons. In the present study, we performed cDNA cloning of rat SH3P7, performed
      RT-PCR analysis, generated polyclonal antibodies against the recombinant rat
      SH3P7 protein, and examined the distribution of SH3P7 in the rat brain using
      immunohistochemistry. Sequence analysis revealed that there were at least four
      isoforms of the SH3P7 protein: SH3P7r1-SH3P7r4. RT-PCR analysis revealed that the
      predominant isoforms expressed in the brain were SH3P7r1 and SH3P7r3. The
      relative levels of isoform expression were similar among regions.
      Immunohistochemistry revealed that the most intense immunolabelling for SH3P7 was
      observed in the hippocampus and cerebellar cortex. Double-labelling studies with
      anti-SH3P7 antibody and other neuronal marker proteins revealed that SH3P7 was
      located primarily in dendrites, and in moderate amounts in cell bodies.
      Immunoreactivity was absent in the presynaptic terminals. In cultured astrocytes,
      SH3P7 was localized at protrusive structures of the cell periphery and in the
      cell body. We concluded that SH3P7 is ubiquitous in the rat brain, and occurs as
      several isoforms. Also, its dendritic localization suggests that SH3P7 is
      functionally linked to actin cytoskeleton organization in dendrites.

PMID- 11595039
TI  - Effects of selective thalamic and prelimbic cortex lesions on two types of visual
      discrimination and reversal learning.
AB  - The effects of excitotoxic lesions of the mediodorsal nucleus of the thalamus,
      the anterior thalamic nuclei and of the prelimbic cortex were examined on two
      tests of discrimination and reversal learning. In experiment 1A (visual
      discrimination and reversal), rats were required to discriminate two stimuli, and
      respond to the stimulus associated with reward (the S+ stimulus). There was no
      effect of lesion on acquisition of this task. However, when stimulus-reward
      contingencies were reversed, animals with lesions of the mediodorsal nucleus of
      the thalamus made significantly more errors than control animals or animals of
      other lesion groups. In experiment 1B (conditional discrimination), animals were
      required to learn a rule of the type 'If stimulus A then go left, if stimulus B
      then go right'. No main effect of lesion on acquisition was observed in this
      experiment. To test the generality of the reversal effect obtained in experiment
      1A, a second cohort of animals with the same lesions was tested on acquisition of
      the visuospatial conditional task immediately postsurgery, followed by the
      reversal of the conditional rule (experiment 2). As in experiment 1B, no main
      effect of lesion group was observed during acquisition of the task. However,
      lesions of the mediodorsal nucleus of the thalamus resulted in a mild impairment
      according to number of sessions required to attain criterion performance of the
      task when the response rule was reversed. The results of the present study
      provide evidence for a role for the mediodorsal nucleus of the thalamus in new
      learning, particularly when stimulus-reward contingencies are reversed.
      Furthermore, they show that the functions of this thalamic nucleus can be
      dissociated from those of the anterior thalamus and the prelimbic cortex.

PMID- 11595040
TI  - Impairment of binocular vision in the adult cat induces plastic changes in the
      callosal cortical map.
AB  - In the primary visual cortex of normally reared adult cat, neurons activated
      through the corpus callosum are almost entirely located at the 17/18 border. They
      display small receptive fields distributed along the central vertical meridian of
      the visual field and are orientation selective. Here we demonstrate that a few
      weeks of monocular deprivation or unilateral convergent strabismus produced in
      adulthood does not modify the cortical distribution of these neurons, but leads
      to an increase of their receptive field size mainly toward the ipsilateral
      hemifield and to a loss of their orientation selectivity. We conclude that
      manipulation of binocular vision in the adult modifies neither the location of
      the primary callosal cortical map nor its retinotopy. In contrast, it induces
      functional plastic changes in this map which lead to a significant widening of
      the area of visual space signalled through the corpus callosum. These plastic
      changes are interpreted as the result of the strengthening of normally hidden
      subthreshold synaptic inputs.

PMID- 11595041
TI  - Strain differences in the behavioural outcome of neonatal ventral hippocampal
      lesions are determined by the postnatal environment and not genetic factors.
AB  - It has been demonstrated that not only do rats neonatally lesioned in the ventral
      hippocampus (VH) develop behavioural hypersensitivity to amphetamine
      postpubertally, but also that the expression of the sensitivity is strain
      specific. For example, excitotoxic VH lesions at postnatal day (PD) 7 lead to
      significant increases in amphetamine-induced locomotion in postpubertal Fischer
      rats, but not in Lewis rats. However, as it is likely that the effect of strain
      differences are due to a combination of genetics and environment, we examined the
      contributions of the environment of the pups in determining the behavioural
      outcome following neonatal VH lesions. Fisher and Lewis rat pups were cross
      fostered at birth, and then at PD7 lesioned bilaterally in the VH with ibotenic
      acid. ANOVA analysis of postpubertal amphetamine-induced locomotor data revealed
      a significant effect of the strain of the dams raising the pups but no effect of
      the strain of the pup. In addition, a post hoc analysis revealed that lesioned
      Fisher or Lewis rats raised by Fisher, but not those raised by Lewis, dams
      demonstrated amphetamine-induced hyperlocomotion relative to nonlesioned
      controls. Observations of the maternal behaviour of Fischer and Lewis dams
      revealed significant differences in the frequency of arched-back nursing between
      the two strains. Interestingly, a correlation of the frequency of arched back
      nursing vs novelty- or amphetamine-induced locomotion revealed that the lesioned
      rats were significantly more affected by increases in arched-back nursing
      compared to the controls. The results suggest that the genetic background of the
      pups does not significantly affect the behavioural outcome following neonatal VH
      lesions; however, the results do suggest an important role of early environmental
      variables on the behavioural outcome of neonatal VH lesions.

PMID- 11595042
TI  - Projections from the superior temporal sulcus to the agranular frontal cortex in
      the macaque.
AB  - The aim of this study was to investigate the organization of the projections from
      the superior temporal sulcus (STS) to the various areas forming the agranular
      frontal cortex. Injections of retrograde neuronal tracers were made in the
      various agranular areas, in nine macaque monkeys. The results showed that two
      rostral premotor areas, F6 (pre-SMA) and F7, and the ventrorostral part of area
      F2 (F2vr) are targets of projections from the upper bank of the STS (uSTS). F6
      and the dorsorostral part of F7 (supplementary eye field, SEF) are targets of
      projections from the rostral part of the uSTS, corresponding to the so-called
      'superior temporal polysensory area' (STP). In contrast, the ventral part of area
      F7 (not including the SEF) and F2vr are targets of afferents from the caudal part
      of the uSTS. Ventral F7 is the target of weak afferents from the caudalmost and
      dorsalmost part of the uSTS (area 7a), whilst F2vr is the target of projections
      from a relatively more rostral and ventral sector of the uSTS, close to the
      fundus of the sulcus. This sector should correspond to area MST. In conclusion,
      F6 and SEF receive high order information from STP, whereas ventral F7 and F2vr
      receive information from areas of the dorsal visual stream.

PMID- 11595043
TI  - Characterization of serial order encoding in the monkey anterior cingulate
      sulcus.
AB  - In a previous report we showed that neurons in the anterior cingulate cortex
      might encode the serial order of the three components (first, second and third)
      of motor sequences, irrespective of which component is performed, and
      irrespective of the component that precedes or follows. Here we further explore
      these data by comparing the magnitude of cell activity at the different ranks. We
      also compare the activity recorded in the motor sequences and in tasks with only
      one motor component. We finally discuss functional hypotheses, which may account
      for the serial order encoding.

PMID- 11595044
TI  - Statistical tests of selective neutrality in the age of genomics.
AB  - Examining genomic data for traces of selection provides a powerful tool for
      identifying genomic regions of functional importance. Many methods for
      identifying such regions have focused on conserved sites. However, positive
      selection may also be an indication of functional importance. This article
      provides a brief review of some of the statistical methods used to detect
      selection using DNA sequence data or other molecular data. Statistical tests
      based on allelic distributions or levels of variability often depend on strong
      assumptions regarding population demographics. In contrast, tests based on
      comparisons of the level of variability in nonsynonymous and synonymous sites can
      be constructed without demographic assumptions. Such tests appear to be useful
      for identifying specific regions or specific sites targeted by selection.

PMID- 11595045
TI  - Additive and non-additive genetic architecture of two different-sized populations
      of Scabiosa canescens.
AB  - Future adaptation to changes in the environment depends on the existence of
      additive genetic variances within populations. Recently, considerable attention
      has also been given to the non-additive component, which plays an important role
      in inbreeding depression and bottleneck situations. In this study, I used data
      from a North Carolina II crossing experiment, analysed with restricted maximum
      likelihood methods, to estimate the additive and dominance genetic (co)variances
      for eight quantitative characters in two different-sized populations of Scabiosa
      canescens, a rare and threatened plant in Sweden. There was no evidence for
      genetic erosion in the small Hallestad population ( approximately 25 individuals)
      relative to the large Ahus population ( approximately 5000 individuals). In fact,
      slightly higher heritabilities were found in the Hallestad population. The
      additive genetic variance was statistically significant for all traits in both
      populations, but only a few additive covariances reached significance. The
      Hallestad population also had higher mean levels and more traits with significant
      dominance variance than the Ahus population. The variance attributable to
      maternal effects was too low to be considered significant. There was only a weak
      correspondence between heritabilities for each trait in the present study and
      previous estimates based on open-pollinated families of the same populations, but
      the mean heritability (over characters) was consistent between the studies.

PMID- 11595046
TI  - Genetics of larval urea and ammonia tolerance and cross-tolerance in Drosophila
      melanogaster.
AB  - Five laboratory populations of Drosophila melanogaster previously selected for
      over 60 generations for larval resistance to ammonium chloride (NH4Cl), and five
      populations selected for over 60 generations for larval resistance to urea, were
      investigated to determine the genetic mechanisms through which such tolerance had
      evolved. To examine the genetics of tolerance to urea and ammonia, egg-to-adult
      survivorship and developmental time were measured at two different NH4Cl levels
      and two different urea levels for each selection regime relative to the control
      lines, and among reciprocal crosses between each selection regime and the control
      lines. To examine tolerance to novel nitrogenous compounds (cross-tolerance), egg
      to-adult survivorship and developmental time were measured at two different NH4Cl
      levels and two different urea levels for reciprocal crosses between the selection
      lines. Dominance is a major genetic factor in egg-to-adult survivorship in the
      presence of either urea or ammonia, while cross-tolerance to novel nitrogenous
      compounds also shows dominance as a major genetic mechanism controlling egg-to
      adult survivorship. Dominance and X-linkage appear to be factors affecting
      developmental time in the presence of either urea or ammonia, although we could
      not exclude cytoplasmic inheritance as influencing our results. Cross-tolerance
      to novel nitrogenous compounds shows dominance and X-linkage as the main genetic
      factors controlling developmental time. We develop a simple hypothesis, in
      accordance with the results, that there may be two X-linked loci: one controlling
      urea tolerance and one controlling ammonia tolerance, and one autosomal locus
      exerting a pleiotropic control of tolerance. However, many other possibilities
      exist.

PMID- 11595047
TI  - Genetic control of the rate of wound healing in mice.
AB  - There have been few studies of the inheritance of wound healing in mammals. In
      this study, we demonstrate that inbred strains of mice differ significantly in
      the rate of wound healing. Of the 20 strains tested, fast healers (MRL/MpJ
      Fas(lpr) and LG/J) healed wounds four times faster than slow healers (Balb/cByJ
      and SJL/J). The genetic basis underlying the difference in the healing capacity
      was analysed using F2 populations of two different crosses. We show that the
      wound healing is a polygenically determined quantitative trait with an average
      estimated heritability of 86%. The modes of gene action in these two crosses are
      different. In the (MRL/MpJ x SJL/J) cross, genes regulating fast healing in
      MRL/MpJ mice exhibited additive effects, whereas these effects were suppressed by
      a dominant repressor gene in CBA/J mice in the (MRL/MpJ-Fas(lpr) x CBA/J) cross.
      Information gained from this investigation provides insight into further study of
      molecular mechanisms underlying the rate of wound healing in mammals.

PMID- 11595048
TI  - The influence of male parr body size and mate competition on fertilization
      success and effective population size in Atlantic salmon.
AB  - Alternative mating strategies in male Atlantic salmon, Salmo salar, are
      characterized by variability in body size and mate competition. Controlling
      breeding numbers of larger, older anadromous males, we examined whether body size
      of mature male parr influenced fertilization success and whether such an
      association was affected by mate competition among parr. Variation at three to
      four hypervariable microsatellite loci was used to determine individual paternity
      of 53-60 offspring from two or three nests from each experimental treatment.
      Although individual and total parr reproductive success differed significantly
      among nests within treatments, there was no relationship between parr size and
      individual reproductive success at any level of competition when anadromous males
      were involved. However, in a single treatment having no anadromous male, the
      influence of body size on parr fertilization success was highly significant.
      Combining data from all treatments, parr body size was an important predictor of
      the probability of an individual being involved in spawning. We found a negative
      relationship between total parr reproductive success and intensity of anadromous
      male competition. To our knowledge, the present study is the first to estimate
      the effective number of males from individual fertilization success in fish. Our
      estimates of Ne should not be taken as absolute and may have a downward bias
      because we did not sample all nests and we used a proxy for lifetime reproductive
      success. They do, however, illustrate how mature male parr can greatly increase
      the effective number of males when the latter is estimated from anadromous
      individuals alone. Although reproductive success by mature male parr increases
      the effective number of males, this increase seems likely to be most pronounced
      in natural populations when the number of anadromous males is low.

PMID- 11595049
TI  - Genetic and environmental contributions to variation in human tooth size.
AB  - Human dental crowns are complex structures without simple genetic or
      environmental determination, but mathematical modelling of data from family
      studies is now providing a more complete picture of their ontogeny. Mesiodistal
      (MD) and buccolingual (BL) dental crown diameters were recorded from almost 600
      monozygotic and dizygotic twins, and univariate biometrical models were fitted to
      the data for 28 permanent teeth (excluding third molars). All 56 variables showed
      significant contributions of additive genetic variation, varying from 56 to 92%
      of phenotypic variation, with most being over 80%. The effects of individual or
      unique environment ranged from 8 to 29%. A significant effect of the environment
      shared by twins--either uterine or early childhood-- was found for MD and BL
      diameters of maxillary first molars (22-27%). There were also significant levels
      of non-additive genetic variation in MD diameters of canines and first premolars,
      which is consistent with selective pressures acting on these teeth at some stage
      in human evolution.

PMID- 11595050
TI  - Fecundity of transgenic wild-crop hybrids of Cucurbita pepo (Cucurbitaceae):
      implications for crop-to-wild gene flow.
AB  - Hybridization between crops and their weedy or wild relatives is an area of
      concern because the widespread use of genetically engineered crops may allow
      novel, beneficial transgenes to enter nearby populations. We compared fitness
      components of wild Cucurbita pepo from Arkansas, USA, with wild-crop hybrids
      derived from yellow squash (a cultivar of C. pepo with transgenic resistance to
      two viruses). Wild and hybrid progeny were grown in agricultural fields in
      Arkansas (1996-98) and Ohio (1996) in six similar experiments. Cross types (wild
      and hybrid) did not differ significantly in seedling survival, which exceeded 85%
      in all cases. In Ohio, where more detailed observations were made, hybrid plants
      produced 41% as many male flowers, 21% as many female flowers, and 28% as many
      seeds as wild plants. At all sites, flowering periods of the two cross types
      overlapped extensively. Putative virus symptoms were more common in wild plants
      than in hybrids. Lifetime fecundity varied considerably among sites and years.
      The average fecundity of hybrids ranged from 453 to 4497 seeds per plant and
      represented 15% - 53% of the numbers of seeds produced by wild plants in the same
      experiments. These results suggest that the F1 generation does not represent a
      strong barrier to the introgression of neutral or beneficial crop genes into free
      living populations of C. pepo.

PMID- 11595051
TI  - The impact of habitat fragmentation and social structure on the population
      genetics of roe deer (Capreolus capreolus L.) in Central Europe.
AB  - Nine out of 57 bovine and caprine microsatellites investigated have proved
      polymorphic in roe deer populations from Central Europe. The polymorphism of four
      to nine microsatellites (with two to 16 alleles each) has been screened in 492
      roe deer from 27 sample locations in Germany, the Netherlands and France, and 10
      allozyme loci have been investigated in 118 roe deer from Germany. These studies
      have revealed a genetically homogeneous population, but with a local scatter of
      allele frequencies. The mean genetic distance among sample pairs, and the overall
      fixation index for the 27 population samples were D=0.1638 and GST=0.0972 for
      four microsatellite loci, and D=0.0598 and GST=0.1459 for 10 allozyme loci. No
      isolation-by-distance was observed. Roe deer from isolated habitats could be
      distinguished by various measures of genetic variability. The expected
      heterozygosity and the allelic diversity were higher in male than in female roe
      deer, but mean genetic distances and fixation indices were higher in females. The
      fixation indices of pairs of adjacent samples, and the genetic distance among
      these samples correlated highly significantly with the density of human
      settlement, measured by the percentage of land surface covered by roads and
      villages. The utility of allozymes and microsatellites for population genetic
      studies in cervids are compared.

PMID- 11595052
TI  - Genetic structure of Siberian lemmings (Lemmus sibiricus) in a continuous
      habitat: large patches rather than isolation by distance.
AB  - In a continuous habitat, restricted dispersal and local genetic drift are likely
      to create a pattern of increasing genetic differentiation with distance. Here, we
      describe the genetic structure of Siberian lemming (Lemmus sibiricus) populations
      in a continuous tundra habitat on the western coast of the Taimyr Peninsula, in
      order to determine the spatial scale at which genetic differentiation and
      isolation by distance occur. Sampling was carried out at three different
      geographical scales: (1) a continuous 11 km transect; (2) localities 10-30 km
      apart; and (3) two localities at 300 and 600 km from the main study area. Two
      types of genetic markers were used: partial sequences of the mitochondrial DNA
      control region and four microsatellite loci. On this basis the study populations
      were genetically quite homogeneous within patches extending over 8 km or more.
      Contrary to theoretical predictions, no pattern of isolation by distance among
      patches could be identified. This observation was interpreted as representing
      populations in migration-drift disequilibrium after a recent major mixing event.
      The lack of concordance between mtDNA haplotype phylogeny and the geographical
      distribution of haplotypes supported this interpretation. Spatial autocorrelation
      among individual genotypes on a local scale was weak and observed only in
      females, indicating a considerable amount of mostly male-mediated gene flow.
      Average gene flow per generation was estimated to be in the range of several
      hundred metres.

PMID- 11595053
TI  - A field cage test of the effects of the endosymbiont Wolbachia on Drosophila
      melanogaster.
AB  - Wolbachia endosymbionts are known to affect the fitness of their hosts, but most
      of this information is from laboratory studies. In Drosophila melanogaster,
      Wolbachia frequencies vary clinically in frequency in Australia and may confound
      climatic adaptation. Here we use field cages in a reciprocal exchange design to
      test for Wolbachia effects in D. melanogaster in winter at temperate and tropical
      sites. Infected flies of both populations had a lower fecundity in tropical north
      Queensland, whilst in temperate southern Victoria Wolbachia effects depended on
      the nuclear population background. Here infected flies from Victoria were more
      fecund. Wolbachia also influenced larval/pupal viability in the tropics but this
      was dependent on population background. In comparisons of the populations, there
      was no evidence for local adaptation for total fecundity, viability or survival
      over winter. However, in Victoria, a local population had a higher late-life
      fecundity than a tropical population from Queensland that had higher early-life
      fecundity. At a tropical site, local Queensland flies had a higher early
      fecundity than Victorian flies. In contrast to many laboratory studies, mortality
      rates in the field cages increased only slightly over time. Both the Wolbachia
      effects and population differences have not been previously detected in
      laboratory studies with D. melanogaster and highlight the utility of Drosophila
      field studies in fitness experiments.

PMID- 11595054
TI  - Evolutionary dynamics and chromosomal distribution of repetitive sequences on
      chromosomes of Aegilops speltoides revealed by genomic in situ hybridization.
AB  - Simultaneous genomic in situ hybridization (GISH) with probe preannealing was
      used to detect the relationship between chromosomal position and sequence
      conservation on Aegilops speltoides var. aucheri chromosomes. DNA of Secale
      sylvestre, Hordeum spontaneum, Festuca pratensis, Semiarundinaria fastuosa,
      Arundo donax and Zea mays that represent several main groups of Poaceae were used
      as probes. Different GISH-banding patterns that characterize diverse evolutionary
      trajectories in the repetitive DNA fraction and correlate with evolutionary
      distance between tested species were observed. Fast-evolving sequences were
      detected in subterminal telomeric and subtelomeric heterochromatic regions,
      whereas sequences in pericentromeric regions showed high levels of conservation.
      GISH experiments revealed extensive conservation in NOR regions on chromosomes 1
      and 6 which, in fact, appears to be a complicated mix of rDNA clusters and
      heterochromatin blocks of different nucleotide composition.

PMID- 11595055
TI  - Is maize B chromosome preferential fertilization controlled by a single gene?
AB  - In previous work, genotypes for high and low B chromosome transmission rate were
      selected from a native race of maize. It was demonstrated that the B transmission
      is genetically controlled. The present work reports the fourth and fifth
      generations of selection and the F1 hybrids between the lines. The native B is
      characterized by a constant behaviour, with normal meiosis and nondisjunction in
      100% of postmeiotic mitosis. It is concluded that genetic variation for B
      transmission between the selected lines is due to the preferential fertilization
      process. The F1 hybrids show intermediate B transmission rate between the lines.
      They are uniform, the variance of the selected character being one order of
      magnitude lower than that of the native population. In addition, 0B x 2B and 2B x
      2B crosses were made to study the effect of the presence of B chromosomes in the
      female parent, resulting in non-significant differences. Several crosses were
      made both in Buenos Aires and in Madrid to compare the possible environmental
      effect, but significant differences were not found. Our results are consistent
      with the hypothesis of a single major gene controlling B transmission rate in
      maize, which acts in the egg cell at the haploid level during fertilization. It
      is also hypothesized that maize Bs use the normal maize fertilization process to
      promote their own transmission.

PMID- 11595056
TI  - Hepatitis B surface antigen-positive organ transplantation recipients: can
      lamivudine alter their fate?

PMID- 11595057
TI  - Soluble Fas modulates interferon responsiveness.

PMID- 11595058
TI  - Alteration of DNA methylation in gastrointestinal carcinogenesis.
AB  - DNA methylation is the main epigenetic modification in humans. The methylation of
      promoter inhibits the transcription in most genes. In normal tissues, isolated
      CpG dinucleotides in bulk chromatin are often methylated, whereas cytosines in
      CpG islands are unmethylated. In neoplasms including gastrointestinal cancer,
      this pattern of methylation is commonly reversed. The alteration of DNA
      methylation plays a key role in the process of carcinogenesis. The
      gastrointestinal carcinogenesis is suggested to be associated with the decrease
      of total genomic DNA methylation; hypomethylation of certain specific oncogenes
      such as c-myc, c-Ha-ras, c-fos and alpha-fetoprotein; and hypermethylation of the
      promoter of some tumor suppressor genes containing p16(INK4A), E-cadherin and
      hMLH1 genes. This review focuses on the analysis methods for methylation, studies
      for aberrant DNA methylation in gastrointestinal carcinogenesis, and the
      intervention changing methylation, including the treatment of 5-azacytidine,
      supplement of folate and gene therapy.

PMID- 11595059
TI  - Seroepidemiological study of Helicobacter pylori infection in asymptomatic people
      in South Korea.
AB  - BACKGROUND: Helicobacter pylori infection occurs throughout the world and causes
      gastroduodenal diseases in all age groups. The prevalence of H. pylori infection
      varies between countries and races. The aim of this study was to evaluate the
      seroprevalence of H. pylori infection in asymptomatic healthy people in South
      Korea. METHODS: From March 1998 to October 1998, 5732 asymptomatic subjects who
      responded to the self-assessment questionnaires from 54 hospitals in South Korea
      were enrolled in this study. The serum levels of antibodies for H. pylori
      immunoglobulinG were measured by using an ELISA test. RESULTS: The overall
      seroprevalence of H. pylori infection was 46.6% and there was no statistical
      difference between males (47.2%) and females (45.9%). In adults, a significant
      difference was observed between genders. According to the geographic areas, the
      high prevalent provinces were Kangwon (53.4%), Cheju (52.9%) and Cholla province
      (50.6%); Seoul (41.9%) was the lowest prevalent area. The seroprevalence
      increased with age and was highest when patients were aged in their 40s (78.5%).
      The characteristic feature of our study was that the infection rate was steeply
      increased in three age groups (10-12 year olds, 16-19 year olds and those aged in
      their 20s). In Seoul, there was no difference in the prevalence rate among the
      districts studied. CONCLUSIONS: This nation-wide seroprevalence of H. pylori
      infection in South Korea was 46.6%, which showed the transition from a developing
      country to a developed country. More studies on the epidemiological factors and
      the route of transmission of H. pylori infection should be warranted.

PMID- 11595060
TI  - An evaluation of the PyloriTek test for the diagnosis of Helicobacter pylori
      infection in Chinese patients before and after eradication therapy.
AB  - BACKGROUND AND AIM: The PyloriTek Test Kit (a 1-h rapid urease test) was
      developed for the rapid diagnosis of Helicobacter pylori (H. pylori) during
      endoscopy. Most studies were performed in Western populations. The aim of this
      study was to evaluate the PyloriTek test for the diagnosis of H. pylori infection
      in Chinese population. METHODS: Eligible patients without prior treatment or who
      had had recent eradication of H. pylori were recruited. During endoscopy,
      biopsies were taken from the antrum and corpus for an in-house rapid urease test
      (RUT), histology and for the PyloriTek test (one antral and one corpus biopsy).
      Results of the PyloriTek test were compared with the gold standard (RUT and
      histology). RESULTS: Analysis of PyloriTek test results from the antrum alone
      (101 patients before eradication and 52 patients after eradication) showed a
      sensitivity, specificity, and accuracy of 96.3, 97.9, and 97.0%, respectively,
      for cases before eradication, and an accuracy of 100% for cases after
      eradication. The benefit of an additional body biopsy was marginal and only
      occurred in the pre-eradication group. CONCLUSION: The PyloriTek test was highly
      accurate for the diagnosis of H. pylori infection before and after eradication
      therapy, with a final result available at 1 h, which is unmatched by any invasive
      test so far. It enhances clinical decision-making by allowing the clinicians or
      endoscopists to start therapy on the same day of an endoscopy visit. One biopsy
      from the antrum is highly reliable for this purpose.

PMID- 11595061
TI  - Antibiotic susceptibility of Helicobacter pylori in the Chinese population.
AB  - AIM: To assess antibiotic susceptibility of Helicobacter pylori (H. pylori)
      strains to metronidazole, clarithromycin and tetracycline in the Chinese
      population, and to test the stability of antibiotic resistance in H. pylori 1
      year after storage at -80 degrees C. METHODS: Fifty H. pylori strains isolated
      from patients with peptic ulcer disease were recovered from storage at -80
      degrees C. Susceptibility of these strains to metronidazole, clarithromycin and
      tetracycline was determined by using validated disk diffusion tests, which was
      repeated 1 year after storage at -80 degrees C. The DNA profiles of each strain
      were determined by using the polymerase chain reaction-based-random amplified
      polymorphic DNA fingerprinting technique (PCR-RAPD). This was repeated if any
      change in antibiotic susceptibility pattern was noticed. RESULTS: The resistance
      rate was 50% to metronidazole and 8% to clarithromycin. None of the strains was
      resistant to tetracycline. A dual resistance to metronidazole and clarithromycin
      was demonstrated in three H. pylori strains. The antibiotic susceptibility test
      reproduced itself in 92% (36 of 39) of the strains 1 year later; the three
      strains with dual resistance exhibited susceptibility to both antibiotics.
      Variation in antibiotic susceptibility pattern in the three H. pylori strains was
      associated with change in the RAPD fingerprint. CONCLUSION: The prevalence of
      resistance in H. pylori is high to metronidazole but low to clarithromycin in the
      Chinese population. The disk diffusion test appears to be a simple and reliable
      test, while antibiotic resistance in some H. pylori strains may disappear after
      long-term storage at -80 degrees C.

PMID- 11595062
TI  - Evaluation of intestinal mucosal function by measuring expired (14)CO(2) after
      oral administration of (14)C-putrescine.
AB  - BACKGROUND: Diamine oxidase (DAO) is the enzyme that degrades putrescine, the key
      main product of polyamine metabolism, and reflects enterocytic maturity of
      absorption because diamine oxidase activity is highest in the small intestine. We
      have already shown that expired (14)CO(2) after oral administration of (14)C
      putrescine correlated with intestinal DAO activity. However, the influence of
      food composition and the mucosal adaptation after intestinal resection have not
      been elucidated. METHODS: Male Wistar rats were fed normal chow or an elemental
      diet (ED) for 2 weeks. Resected rats underwent 50% jejunectomy or 50% ilectomy.
      Expired (14)CO(2) levels, following oral administration of (14)C-putrescine were
      measured in all rats, and compared with the intestinal DAO activity and other
      mucosal parameters. RESULTS: In the ED group, the (14)CO(2) levels reached a peak
      earlier, and values were 2.9-fold higher than in the group fed with normal chow.
      Mucosal alkaline phosphatase (ALP) and DAO activity in the ED group were also
      higher than in the group fed normal chow, although the mucosal wet weight was
      significantly lower in the ED group. In the resection groups, all expired
      (14)CO(2) values increased during measurement. The peak (14)CO(2) values in the
      jejunectomy group shifted earlier in the postoperative period. The mucosal DAO
      activity in both the resection groups was higher than it was in the control group
      at the fifth and 10th postoperative day. However, there were no differences among
      the three groups at the 15th postoperative day. CONCLUSIONS: Our studies
      suggested that expired (14)CO(2) after oral administration of (14)C-putrescine
      correlates with mucosal DAO activity, and that it also reflects intestinal
      function.

PMID- 11595063
TI  - Expression of interleukin-6, leukemia inhibitory factor and their receptors by
      colonic epithelium and pericryptal fibroblasts.
AB  - BACKGROUND AND AIM: The cellular configuration of the human colon suggests a
      predetermined organization that creates specific microenvironments. The role of
      pericryptal fibroblasts in this microenvironment has been the subject of
      considerable speculation. This study examined the expression of growth factors
      and their receptors by colonic crypt epithelium and pericryptal fibroblasts.
      METHODS AND RESULTS: Pericryptal fibroblast cells were isolated and cultured from
      decrypted human colonic mucosa. The pericryptal fibroblast cells expressed
      messenger RNA (mRNA) for interleukin-6 (IL-6), leukemia inhibitory factor (LIF),
      LIF receptor alpha, and the common coreceptor glycoprotein 130 (GP130), but not
      the IL-6 receptor alpha. Interleukin-6 protein expression was confirmed by the
      analysis of conditioned medium and immunohistochemistry. In comparison, normal
      colonic epithelial cells express mRNA for LIF but not IL-6 as well as the
      receptors for GP-130, IL-6 receptor alpha but not LIF receptor alpha. As cultures
      of normal human colonic epithelial cells were not available, the conditioned
      medium was assayed from established colon carcinoma cell lines and demonstrated a
      secretion of LIF but not IL-6 protein. CONCLUSION: The expression of reciprocal
      cytokine and receptor expression suggest that there is a paracrine relationship
      between pericryptal fibroblasts and colonic epithelium.

PMID- 11595064
TI  - Lamivudine treatment for hepatitis B reactivation in HBsAg carriers after organ
      transplantation: a 4-year experience.
AB  - BACKGROUND: Reactivation of hepatitis B after organ transplantation in hepatitis
      B surface antigen (HBsAg) carriers may be fatal. In this study, we reported our
      experience of lamivudine treatment in HBsAg carriers who had post-transplant
      reactivation of hepatitis B. METHODS: The patients were 15 men and one woman.
      Nine received kidney transplants, six received heart transplants, and one
      received a lung transplant. They developed a reactivation of hepatitis B 1-101
      months (median, 14 months) after transplantation. They received lamivudine 100 mg
      daily on a compassionate-use basis, and had regular follow ups. The median
      pretreatment total serum bilirubin level was 3.0 mg/dL, and the alanine
      aminotransferase level was 357 U/L. Four of the 16 patients were positive for
      HBeAg. The serum hepatitis B virus (HBV) DNA levels were > 3000 pg/mL in 13 (81%)
      patients. Three were coinfected with hepatitis C virus. RESULTS: The overall
      survival rate was 75%. All four fatal cases had a pretreatment total serum
      bilirubin level of > or = 3 mg/dL. Serum HBV-DNA soon became undetectable in 12
      survivors. Of the 12 survivors, after a median treatment period of 101 weeks, a
      lamivudine-resistant strain with variation in the YMDD motif of the HBV
      polymerase gene developed in three (25%). None had significant adverse reactions
      to lamivudine treatment. CONCLUSIONS: These results indicated that lamivudine is
      effective in the treatment of post-transplant hepatitis B reactivation, including
      patients with dual chronic hepatitis B and C. Early recognition of HBV
      reactivation and prompt lamivudine treatment are important to prevent mortality.

PMID- 11595065
TI  - Significance of serum soluble Fas antigen level in chronic hepatitis C patients
      treated with interferon: relationship to the therapeutic response.
AB  - BACKGROUND AND AIM: Fas system-mediated cytotoxicity is thought to be involved in
      the development of liver injury in hepatitis C virus (HCV) infection. In this
      study, we investigated serum soluble Fas antigen levels in chronic hepatitis C
      patients treated with interferon and their correlation with the therapeutic
      response. METHODS: The subjects were 67 chronic hepatitis C patients who
      underwent a 24-week course of alpha-interferon therapy. Patients were categorized
      into three groups; sustained responders (n = 22), transient responders (n = 24),
      and non-responders (n = 21), according to changes in the serum alanine
      aminotransferase level during and after therapy. The viral genotype, viremic
      level and diversity in the hypervariable region were examined before therapy.
      Serum soluble Fas antigen levels were assayed by using serum samples taken at the
      beginning and the end of therapy. RESULTS: In the univariate analysis, serum
      soluble Fas antigen levels tended to be higher in non-responders (10.0 +/- 3.4
      ng/mL) than in sustained responders (8.5 +/- 3.0 ng/mL) and transient responders
      (8.2 +/- 2.1 ng/mL; P = 0.13 and P < 0.05). The non-response to therapy was
      observed in eight of the 15 (53%) patients with serum soluble Fas antigen > or =
      11 ng/mL, compared with 13 of the 52 (25%) patients with serum soluble Fas
      antigen < 11 ng/mL (P < 0.05). As for the multivariate analysis, the only
      significant factor contributing to the sustained response was a low HCV viremic
      level (P = 0.0046). Significant factors contributing to the non-response were a
      high serum alanine aminotransferase (P = 0.0407) and a high serum soluble Fas
      antigen level (P = 0.0483). CONCLUSIONS: High production levels of soluble Fas
      antigen may be associated with a poor response to interferon therapy in chronic
      hepatitis C patients.

PMID- 11595066
TI  - Long-term histological prognosis and serum fibrosis markers in chronic hepatitis
      C patients treated with interferon.
AB  - BACKGROUND: Interferon (IFN) therapy is effective in 20-40% of patients with
      chronic hepatitis C, but the relationship between histological changes and the
      response to interferon is still unclear. We investigated the long-term
      histological prognosis and the changes of serum fibrosis markers after interferon
      therapy relation to the response. METHODS AND RESULTS: One hundred and eighteen
      patients with chronic hepatitis C who received interferon therapy were divided
      into four groups based on the detection of viremia and the serum alanine
      aminotransferase (ALT) level after treatment. A histological examination was
      performed by using the histological activity index and the criteria of the
      METAVIR score. Serum fibrosis markers were used to measure the levels of
      hyaluronic acid and type IV collagen 7s. Responders, whose serum ALT levels
      became normal after treatment, demonstrated histological improvement.
      Histological improvement was more rapid in sustained virological responders with
      hepatitis C virus (HCV) RNA seronegativity than in biochemical responders with
      HCV-RNA seropositivity. Only sustained virological responders exhibited
      histological cure. In partial responders, whose serum ALT levels decreased to
      less than twice the upper of normal, and non-responders whose serum ALT levels
      were not reduced, liver fibrosis was unchanged or showed progression. Serum
      fibrosis markers increased with progression of the histological stage and varied
      depending on the response to interferon. CONCLUSION: Normalization of serum ALT
      levels after interferon therapy led to a histological improvement, and that with
      viral clearance achieved histological cure. Serum fibrosis markers were useful
      indicators for long-term according to the response of IFN therapy.

PMID- 11595067
TI  - Calcium-parathyroid hormone-vitamin D axis and metabolic bone disease in chronic
      viral liver disease.
AB  - BACKGROUND: The main process involved in hepatic osteodystrophy seems to be
      osteoporosis, but decreased 25-hydroxylation of vitamin D might lead to
      osteomalacia and secondary hyperparathyroidism. METHODS AND RESULTS: We studied
      bone mineral density (BMD) by using DEXA-Expert Lunar, biochemical markers of
      bone turnover and calcium-parathyroid hormone (PTH)-vitamin D axis in 100
      patients with chronic viral hepatitis secondary to hepatitis C virus: 49 non
      cirrhotic (NCir) and 51 with cirrhosis (Cir) confirmed by liver biopsy and/or
      clinical and biochemical features. When compared to the age-matched population,
      25% of the patients had low BMD at the lumbar spine (LS), 26.2% at Ward's
      triangle, 15.5% at the femoral neck (FN), and 20.2% at the trochanter. No
      difference was found either between Cir and NCir groups or between sexes. Urinary
      N-telopeptide was increased in 31.86% of the patients, and negatively correlated
      with BMD at the LS and trochanter (P < 0.02). Serum bone-specific alkaline
      phosphatase was elevated in 21% of the patients and negatively correlated with
      BMD at the trochanter and Ward's triangle (P < 0.02). Fasting 25-hydroxyvitamin D
      was low in only three Cir patients, with no difference between the Cir and NCir
      groups, but it was higher in men (51.8 +/- 16.0 ng/mL) compared to women (40.4 +/
      14.4 ng/mL; P = 0.001). Fasting serum calcium was lower in Cir than NCir
      patients, P = 0.019. Fasting intact PTH was elevated in 42% of the patients, but
      the mean serum levels were similar in Cir and NCir groups. CONCLUSION: We found
      no evidence of vitamin D deficiency, but cannot exclude the participation of PTH
      in the high bone turnover and bone loss in the population with chronic viral
      hepatitis.

PMID- 11595068
TI  - Safety of an ofloxacin-based antitubercular regimen for the treatment of
      tuberculosis in patients with underlying chronic liver disease: a preliminary
      report.
AB  - BACKGROUND AND AIMS: Hepatotoxicity is a major side-effect of antitubercular
      drugs (ATD). As these drugs are metabolized in the liver, there is a theoretical
      risk of increased hepatotoxicity in patients with underlying chronic liver
      disease (CLD). Ofloxacin has antitubercular activity and has exclusive renal
      clearance. The aim was to study the efficacy and safety of an ofloxacin-based
      antitubercular regimen for treating tuberculosis in patients with underlying CLD.
      METHODS: Thirty-one cases were randomly assigned to two drug regimens using WHO
      dosage schedules: (i) regimen A (n = 15): isoniazid, rifampicin and ethambutol
      for 2 months, followed by isoniazid and rifampicin for a further 7 months; and
      (ii) regimen B (n = 16): isoniazid, pyrazinamide, ethambutol and ofloxacin for 2
      months, followed by isoniazid, ethambutol and ofloxacin for a further 10 months.
      Hepatotoxicity was diagnosed if alanine aminotransferase/aspartate
      aminotransferase increased > fivefold from the baseline or to > 400 IU/L, or if
      bilirubin increased by > 2.5 mg/dL from the baseline. RESULTS: The response to
      ATD was achieved in all the patients who completed the therapy. Four (26.6%)
      patients on regimen A developed hepatotoxicity as compared to none on regimen B
      (P = 0.043). None of these patients could be restarted on ATD using the same
      regimen A because of the persistently deranged liver functions. CONCLUSIONS: In
      patients with tuberculosis who have underlying CLD: (i) an ofloxacin-based
      antitubercular regimen without rifampicin is as effective as a rifampicin-based
      regimen; and (ii) a combination of isoniazid with rifampicin is more hepatotoxic
      than a combination with ofloxacin and pyrazinamide.

PMID- 11595069
TI  - Increased risk of antituberculosis drug-induced hepatotoxicity in individuals
      with glutathione S-transferase M1 'null' mutation.
AB  - BACKGROUND: Pathogenesis and genetic factors influencing predisposition to
      antituberculosis drug (ATD)-induced hepatotoxicity are not clear. Polymorphism at
      the genetic locus of a drug and xenobiotic compound metabolizing enzyme, N
      acetyltransferase type 2 (NAT2), is reported to be associated with the excess
      generation of toxic reactive metabolites. Polymorphisms at the glutathione S
      transferase (GST) loci (GSTM1 and GSTT1) are involved in the detoxification of
      these toxic metabolites in the human body to a lesser extent. We have examined
      whether polymorphisms at these loci are associated with the risk of ATD-induced
      hepatotoxicity. METHODS: In this case-control study, 33 pulmonary tuberculosis
      patients with ATD-induced hepatotoxicity and 33 pulmonary tuberculosis patients
      receiving ATD drugs without any evidence of hepatotoxicity were considered as
      cases and controls, respectively. Point mutations at NAT2 and homozygous 'null'
      mutations at GSTM1 and GSTT1 genes were looked into genomic DNA, isolated from
      peripheral blood mononuclear cells by using polymerase chain reaction (PCR).
      RESULTS: The frequency of homozygous 'null' mutation at the GSTM1 gene was
      significantly higher among cases (n = 17, 52%) than controls (n = 8, 24%) (P <
      0.05, relative risk 2.13, 95% CI: 1.25-3.10). Frequencies of mutations at GSTT1
      and NAT2 genes did not differ significantly between cases and controls.
      CONCLUSION: Homozygous 'null' mutation at the GSTM1 gene might predispose an
      individual to ATD-induced hepatotoxicity.

PMID- 11595070
TI  - Hyposplenism in alcoholic cirrhosis, facts or artifacts? A comparative analysis
      with non-alcoholic cirrhosis and extrahepatic portal venous obstruction.
AB  - BACKGROUND AND AIMS: Hyposplenism has been described in patients with alcoholic
      cirrhosis (AC). However, no data are available regarding hyposplenism in patients
      with non-alcoholic cirrhosis (NAC) and other forms of portal hypertension such as
      extrahepatic portal venous obstruction (EHPVO). The aim is to study the splenic
      functions in patients with AC, NAC, and EHPVO. METHODS: Splenic functions were
      assessed consecutively in 22 patients with AC, 21 with NAC, and 23 with EHPVO.
      The tests included pitted red blood cells (RBC; %) and Howell-Jolly bodies in the
      peripheral smear. Pitted RBCs > 2% with or without the presence of Howell-Jolly
      bodies were taken as indicators of hyposplenism. The splenic function in each
      group was compared with age-matched controls. RESULTS: Hyposplenism was found in
      10 (45.45%) patients with AC, six (28.57%) with NAC and one (4.34%) with EHPVO.
      The mean pitted RBCs were significantly increased in patients with AC (mean 4.93
      +/- 1.36% vs control 1.22 +/- 0.17%, P < 0.05), but not so with NAC (2.01 +/-
      0.69%) and EHPVO (mean 0.99 +/- 0.1% vs control 0.66 +/- 0.1%, P > 0.05). Howell
      Jolly bodies were seen in only four patients. The mean pitted RBCs were
      significantly higher among patients who were actively consuming alcohol (9.14 +/-
      3.35%) compared to those who abstained at least for more than 24 weeks (2.0 +/-
      1.3%, P < 0.05). CONCLUSION: Hyposplenism is more common in AC patients,
      particularly those who are actively consuming alcohol compared with those who
      abstain. Patients with NAC have a lower incidence of hyposplenism, while in EHPVO
      patients, it is uncommon.

PMID- 11595071
TI  - Cisapride improves gallbladder emptying in patients with type 2 diabetes
      mellitus.
AB  - BACKGROUND AND AIMS: Gallbladder motor function is impaired in many patients with
      diabetes, and may be related to cholinergic nerve damage. Cisapride is a
      prokinetic drug of the gastrointestinal tract and acts by releasing acetylcholine
      from cholinergic nerve endings. The aim of this study was to determine the effect
      of cisapride on gallbladder emptying in patients with type 2 diabetes mellitus
      (DM). METHODS: Gallbladder emptying and tests for autonomic neuropathy (AN) were
      performed in 27 patients with type 2 DM and in 10 healthy subjects. Gallbladder
      emptying was studied by using real-time ultrasonography after an overnight fast,
      and after the subjects received a breakfast that contained 2500 J. Gallbladder
      emptying was repeated after the treatment with cisapride (10 mg t.i.d.) for 1
      week in all subjects. RESULTS: Abnormal gallbladder emptying was present in 14
      (51.9%) patients. The residual gallbladder volume (mean +/- SEM) was higher (9.3
      +/- 1.0 vs 4.6 +/- 0.6; P = 0.002), and ejection fraction was lower (57.4 +/- 4.0
      vs 74.2 +/- 2.4; P = 0.015) in diabetic patients than it was in healthy subjects.
      Cisapride produced a reduction in fasting and residual volumes (24.6 +/- 2.4 vs
      20.0 +/- 1.4; P = 0.034 and 9.3 +/- 1.0 vs 5.9 +/- 1.1; P = 0.00003,
      respectively), and an improvement in ejection fraction (57.4 +/- 4.0 vs 72.6 +/-
      3.8; P = 0.000007). The improvement in gallbladder emptying after cisapride
      therapy was confined to the patients with AN (n = 13) (57.3 +/- 5.4 vs 80.4 +/-
      2.9; P = 0.0017), suggesting denervation supersensitivity with an upregulation of
      cholinergic receptors. There was no significant change in the ejection fraction
      in patients without AN (57.5 +/- 6.1 vs 65.4 +/- 6.5; P = NS). Sex, duration of
      diabetes, peripheral neuropathy, diabetic retinopathy and serum cholesterol level
      did not influence gallbladder emptying. CONCLUSION: Impaired gallbladder emptying
      is common in patients with type 2 DM. Cisapride significantly improves
      gallbladder emptying in patients with autonomic neuropathy.

PMID- 11595072
TI  - An audit of metal stent palliation for malignant biliary obstruction.
AB  - BACKGROUND AND AIMS: Endoscopic stent insertion is the optimum method of
      palliation for malignant biliary obstruction. Metal stents have several
      advantages over the polyethylene alternatives, but are significantly more
      expensive. It has been reported that patients need to survive beyond 6 months to
      make metal stents more cost-effective. The aim of this study was to audit the
      performance of expanding metal biliary stents in our endoscopy unit, and to
      identify factors that might help with patient selection. METHODS: The records of
      all patients who were selected for endoscopic metal stent insertion at the Royal
      Perth Hospital for malignant biliary obstruction between September 1994 and
      November 1998 were reviewed. RESULTS: Thirty-two patients (16 males, mean age 71
      years (range 34-88 years) were identified and followed up for a mean 201 days
      (range 3-810 days). Fifteen (47%) had cholangiocarcinoma, 13 (41%) had pancreatic
      cancer, and four had metastatic disease as the cause of obstruction. Mortality
      rates after metal stent insertion were 16, 41 and 55% at 30, 90 and 180 days,
      respectively. In total, 24 (75%) patients died during the follow-up period.
      Eleven (34%) stents became obstructed during follow up with a median time to
      occlusion of 125 days (range 44-729 days). Patients with cholangiocarcinoma had
      significantly longer survival than pancreatic cancer cases (median 286 vs 58
      days, P = 0.04). No other factors were found to correlate with the survival or
      stent complications. CONCLUSIONS: Less than half of this mixed cohort survived
      beyond 6 months. Metal stent palliation of malignant biliary obstruction should
      probably be targeted at those with cholangiocarcinoma, as these patients tend to
      survive longer.

PMID- 11595073
TI  - Incidence, spectrum and antibiotic sensitivity pattern of bacterial infections
      among patients with acute pancreatitis.
AB  - BACKGROUND AND AIM: Secondary infection of pancreatic necrotic tissue and
      peripancreatic fluid is a serious complication of acute pancreatitis resulting in
      significant morbidity and mortality. The aim of this study was to find out the
      spectrum of bacterial infections, and their antibiotic sensitivity pattern in
      patients with acute pancreatitis. METHODS: All consecutive patients with acute
      pancreatitis were studied prospectively. Detailed investigations were carried out
      to identify bacterial infections and their antibiotic sensitivities in patients
      with suspected infection. These investigations included cultures of various body
      fluids, throat swabs, indwelling cannula and catheter tips. Pancreatic tissue was
      obtained by using needle aspiration or at surgery for Gram's stain, culture and
      sensitivity. All cultures were repeated until the presence of infection was
      confirmed or excluded. RESULTS: A total of 169 patients with acute pancreatitis
      were studied during the period between January 1997 and June 2000 (mean age 41.3
      years; 116 males and 53 females). Of the 169 patients, 63 had infections at
      various sites. A total of 80 cultures were positive, and 12 different bacterial
      isolates were cultured from samples taken from these 63 patients. Polymicrobial
      infection was seen in 32% of patients. Twenty-four patients had a confirmed
      pancreatic infection. Blood cultures had a growth of organisms in 19 patients,
      with evidence of ongoing or worsening pancreatitis, thus raising a strong
      suspicion of infected necrosis in them. The commonest organisms were Escherichia
      coli from 20 cultures and Pseudomonas aeruginosa from 18 cultures. The antibiotic
      sensitivity pattern showed that most bacteria were sensitive to third generation
      cephalosporins and quinolones; notably among them were cefotaxime, ceftazidime,
      and ciprofloxacin. CONCLUSION: Bacterial infections were seen in 37% of patients
      with acute pancreatitis. The commonest organisms were Pseudomonas aeruginosa and
      Escherichia coli. Most bacterial isolates were sensitive to third generation
      cephalosporins and quinolones.

PMID- 11595074
TI  - Ligation of the Fas antigen stimulates chemokine secretion in pancreatic cancer
      cell line PANC-1.
AB  - BACKGROUND AND AIM: The role of chemokines in the process of immune cell
      infiltration into pancreatic cancer tissue has been reported. In this study, we
      investigated the induction of chemokines (interleukin (IL)-8 and monocyte
      chemoattractant protein (MCP)-1) by Fas antigen (Ag)-stimulation in a human
      pancreatic cancer cell line, PANC-1. METHODS: The chemokine secretion was
      evaluated by using an ELISA and a northern blot, and the activation of nuclear
      factor-kappa B (NF-kappa B) was assessed by using an electrophoretic gel mobility
      shift assay (EMSA). RESULTS: The Fas antigen (Ag) stimulation clearly induced an
      increase in IL-8 and MCP-1 secretion in PANC-1 cells. This effect was also
      observed at the mRNA level. The induction of chemokine secretion by Fas Ag
      stimulation required de novo gene expression and protein synthesis. The
      pretreatment with interferon (IFN)-gamma markedly enhanced the effects of Fas Ag
      stimulation; IFN-gamma pretreatment and Fas Ag stimulation synergistically
      induced not only apoptosis but also IL-8 and MCP-1 secretion. Flow cytometric
      analysis demonstrated that IFN-gamma significantly enhanced Fas Ag expression. In
      addition, Fas Ag stimulation actually evoked NF-kappa B activation in this cell
      line. CONCLUSION: Our results indicate that Fas Ag stimulation can induce
      chemokine secretion in PANC-1 cells, suggesting the contribution of Fas
      stimulation to the accumulation of immune cells in pancreatic cancer tissue.

PMID- 11595075
TI  - Gastrointestinal: gastric inflammatory fibroid polyp.

PMID- 11595076
TI  - Hepatobiliary and pancreatic: a woman with recurrent idiopathic acute
      pancreatitis. Intraductal papillary mucinous tumor of the pancreas.

PMID- 11595077
TI  - Solitary pancreatic tuberculosis in immunocompetent patients mimicking pancreatic
      carcinoma.
AB  - In this study, two cases of biopsy-proven pancreatic tuberculosis are reported.
      The patients presented with fever, anorexia, fatigue, abdominal pain and weight
      loss. A differential diagnosis of fever of unknown origin was conducted. Computed
      tomography (CT) revealed a cystic mass image in the pancreatic head in one
      patient, and a hypodense lesion in the pancreatic head in the other. The first
      patient was diagnosed by a wedge biopsy specimen obtained in the exploratory
      laparotomy. The other patient was diagnosed by percutaneous fine-needle
      aspiration biopsy. Both patients were successfully treated with quadruple
      antituberculous therapy for 12 months. We concluded that especially in young
      patients who present with a mass in the pancreas, pancreatic tuberculosis should
      be considered among the differential diagnoses, particularly in developing
      countries and immunosuppressed individuals.

PMID- 11595079
TI  - Epidemiological aspects of hepatitis C in Portugal.

PMID- 11595080
TI  - A case of squamous cell carcinoma of the pancreas with an initial symptom of
      tarry stool.

PMID- 11595081
TI  - Functional outcomes and quality of life in patients with brain tumours: a review
      of the literature.
AB  - OBJECTIVE: To review the literature with respect to functional outcomes and
      quality of life as it pertains to individuals with brain tumours. MAIN OUTCOMES:
      Most functional outcome papers have focused on acute inpatient rehabilitation. In
      general, patients with brain tumours have comparable rates of functional gains as
      other models of neurologic disability. Tumour type and concomitant treatment do
      not impact functional outcome. Functional independence may predict survivability
      in certain populations. Numerous instruments are used to measure the multiple
      facets of quality of life. Depression, anger and fatigue can impact both physical
      and psychological aspects of quality of life. The physical and functional aspects
      can vary depending on the tumour type. Treatment regimens can negatively impact
      quality of life. CONCLUSION: Brain tumour patients experience changes in function
      and quality of life during their disease course. Rehabilitation services may
      offer a unique opportunity to influence both functional outcome and more closely
      assess quality of life in these individuals.

PMID- 11595082
TI  - Age and functioning after mild traumatic brain injury: the acute picture.
AB  - HYPOTHESIS: There will be acute harbingers of poor outcome following mild
      traumatic brain injury (TBI) in the elderly. PARTICIPANTS: Twenty-six subjects
      age 60 and over were compared to 30 subjects aged 18-59, seen within 1 month, on
      average, following a mild TBI. MAIN OUTCOME MEASURES: Functioning was assessed
      using the Glasgow Outcome Scale (GOS), a global measure of outcome, as well as
      self-report measures of psychosocial functioning, physical symptoms and
      psychological distress. RESULTS: Contrary to the hypothesis, the older group did
      better than their younger counterparts on the GOS (p = 0.002), and reported less
      psychosocial impairment (p < 0.0001), less psychological distress (p = 0.002),
      and less physical symptoms (p = 0.005). However, once employment was controlled
      for, these results only approached statistical significance. DISCUSSION: The
      assumption that elderly subjects have a worse outcome following TBI needs to be
      reconsidered, at least within the acute recovery period. The importance of
      psychosocial factors as modifiers of outcome according to age are emphasized.
      Whether this finding holds true over a longer follow-up period is the subject of
      ongoing research.

PMID- 11595083
TI  - The association between mild traumatic brain injury and psychiatric conditions.
AB  - The majority of patients with mild traumatic brain injury (TBI) recover fairly
      quickly and are usually restored to their previous level of functioning. However,
      a significant minority have prolonged, complicated, or incomplete recoveries and
      have outcomes disproportionately worse than would have been predicted by the
      objective facts of the injury. This failure to recover as expected was the focus
      of this study. The participants were 80 adults with actual or suspected mild TBI
      who were referred to an outpatient mild TBI clinic. Most were characterized by
      problematic recoveries. The results indicated that those individuals who only had
      brain injuries made good recoveries, but that those with psychiatric comorbidity
      did not (chi(2) = 19.65, p = 0.0002). Most of the new psychiatric conditions
      responsible for poor recovery consisted of depression, anxiety disorders or
      conversion disorder. Dissociative phenomena appeared common after mild TBI and
      scores on the Dissociative Experiences Scale predicted brain injury outcome with
      77% accuracy.

PMID- 11595084
TI  - Amnesia, neuroendocrine levels and PTSD in motor vehicle accident victims.
AB  - PRIMARY OBJECTIVE: To examine the initial neuroendocrine responses and subsequent
      PTSD symptomatology among amnesic and non-amnesic victims of motor vehicle
      accidents. It was hypothesized that amnesic patients would be less likely to meet
      PTSD criteria at 1 month follow-up and would display lower catechalomine levels
      and higher basal cortisol than non-amnesics. METHODS AND PROCEDURE: Fifteen-hour
      urinary hormone samples were collected from 70 MVA victims upon hospital
      admission. Participants were assessed for PTSD symptomatology 1 month later. MAIN
      OUTCOMES AND RESULTS: Amnesic patients displayed lower NE/cortisol ratios than
      non-amnesics, were less likely than non-amnesics to develop PTSD, and displayed
      fewer PTSD symptoms than non-amnesics. CONCLUSIONS: Amnesics may physiologically
      experience a motor vehicle accident differently from non-amnesics and have lower
      subsequent PTSD incidence. These results provide partial support for the
      hypothesis that amnesia for a traumatic event can serve as a buffering function
      in the development of subsequent PTSD among MVA victims.

PMID- 11595085
TI  - Short-term durability and improvement of function in traumatic brain injury: a
      pilot study using the Paediatric Evaluation of Disability Inventory (PEDI)
      classification levels.
AB  - PRIMARY OBJECTIVE: To describe the short-term durability and improvement of
      functional outcomes for children and adolescents with traumatic brain injury
      (TBI) up to 6 months after discharge from inpatient rehabilitation. RESEARCH
      DESIGN: Retrospective, descriptive. METHODS AND PROCEDURES: Twenty-five (28.1%)
      of 89 children discharged from inpatient rehabilitation were available for
      outpatient follow-up within 6 months. The Paediatric Evaluation of Disability
      Inventory (PEDI) functional skill classification levels in the domains of self
      care, mobility, and social function, recorded at discharge and follow-up, were
      examined using the Wilcoxon matched pairs signed rank test (two-tailed). MAIN
      OUTCOMES AND RESULTS: Most (64-80%) of the children sustained the outcome level
      achieved at hospital discharge in one or more of the three domains. Significant
      differences (p < 0.05) from discharge to follow-up were detected in mobility and
      social function levels. Differences between children with and without follow-up
      were non-significant in all but one variable (social function level at hospital
      discharge). CONCLUSIONS: The results of this study suggest that children after
      TBI sustain outcomes achieved during inpatient rehabilitation and make
      significant gains in mobility and social function skills within 6 months of
      returning home. More research is needed to predict those children who will
      continue to recover and to identify factors that facilitate recovery in the
      community setting.

PMID- 11595086
TI  - Pilot study of electrical stimulation on median nerve in comatose severe brain
      injured patients: 3-month outcome.
AB  - PRIMARY OBJECTIVE: To determine if electrical stimulation (ES) benefits (waking
      time, 3-month outcomes) treated coma patients. RESEARCH DESIGN: Double blind
      randomized-controlled study. METHODS AND PROCEDURES: Ten coma patients; six
      treatment and four controls, using the 'Respond Select' by EMPI. EXPERIMENTAL
      INTERVENTIONS: Treatment group received radial nerve ES applied in 300 ms
      intermittent pulses at 40 Hz, 15-20m A 8 hours a day up to 14 days of coma;
      control group received sham stimulation. MAIN OUTCOMES AND RESULTS: ES group
      emerged from coma mean 2 days earlier than controls, although this result was not
      statistically significant. At 3 months post-injury, there was no group difference
      in Glasgow Outcome Scale, although the ES group had improved function over
      controls as measured by the FIM/FAM (mean of 114 and 64.5, respectively, n.s.).
      CONCLUSIONS: These data show an interesting trend, although statistical power was
      limited in this small pilot study, suggesting the need for a larger trial.

PMID- 11595087
TI  - Post-stroke violent adventitial movement responsive to levo-dopa/carbi-dopa
      therapy.
AB  - Previous reports in the literature concerning cerebrovascular accident have
      illustrated cases of post-stroke tremor. Treatments of these studies have varied.
      Trials of levo-dopa have been reported in two such cases. This case study reports
      on a case of a patient with a left thalamic, left superior cerebellar artery
      infarction with a lacunar infarction in the basal ganglia. The patient developed
      a violent tremor/movement disorder which was unresponsive to haloperidol. With
      this failure, and with the evidence of a basal ganglion lesion, levo-dopa/carbi
      dopa was introduced as an intervention. The amplitude of the tremor was
      dramatically reduced, with protective devices removed, and with complete
      cessation of the tremor at rest. The medication was withdrawn and reintroduced
      with a reduction and subsequent resolution of the symptoms. A discussion of the
      previous studies of movement disorder with cerebrovascular accident is included.

PMID- 11595088
TI  - Dysautonomia syndrome in the acute recovery phase after traumatic brain injury:
      relief with intrathecal Baclofen therapy.
AB  - In the initial phase of severe head injury, dysautonomic abnormalities are
      frequent. Within the framework of a prospective study, evaluating the efficacy of
      continuous intrathecal Baclofen therapy (CIBT) on hypertonia during the initial
      recovery phase of severe head injury, the authors report on the preliminary
      results of this treatment on paroxysmal dysautonomia about four patients.
      Continuous intrathecal Baclofen infusion was first delivered, for a test period,
      continuously for 6 days. If a relapse of dysautonomia occurred at the end of the
      test period, an implantation of a continuous intrathecal infusion pump delivering
      Baclofen was performed. Results were assessed with four continuous variables;
      duration (days), dose of Baclofen per day (microg/d), number of dysautonomic
      paroxysmal episodes per day, and initial recovery evaluated by a scale of the
      first initial stages of head injury coma recovery. For three patients: (1) the
      number of dysautonomic paroxysmal episodes per day and the doses of Baclofen
      during the follow-up period were correlated (p = 0.02, p < 0.001, p = 0.008,
      respectively, distribution-free test of Spearman), (2) during the test period and
      the relapse after the test period, the number of paroxysmal episodes and the
      Baclofen dose are correlated to p < 0.05, p = 0.03, p = 0.04, respectively
      (distribution-free test of Spearman). The second statistical test was used to
      prove that Baclofen doses and number of paroxysmal dysautonomic episodes are
      correlated independently of the duration of follow-up. The fourth patient
      improved with CIBT without any recurrence at the end of the treatment test
      period. For the four patients, recovery score increased during the overall follow
      up. In the authors' experience CIBT is very efficient to control paroxysmal
      dysautonomia during the initial recovery phase in severe head injury, and seems
      to facilitate recovery.

PMID- 11595089
TI  - Transient crossed aphasia and persistent amnesia after right thalamic
      haemorrhage.
AB  - A 45-year-old right-handed woman suffered transient aphasia and persistent
      amnesia after a right thalamic haemorrhage. This patient appeared to have crossed
      aphasia, although it disappeared within 8 weeks. It is noteworthy that the
      patient had a unilateral right thalamic lesion but exhibited both verbal and non
      verbal memory impairment. Computed tomography and magnetic resonance imaging
      revealed cerebral haemorrhage in the right thalamus involving the ventral
      anterior nucleus, medioventral nucleus, mamillothalamic tract, internal medullary
      lamina, and mediodorsal nucleus. An amytal test was performed and suggested that
      the right hemisphere was dominant for language functions and the left hemisphere
      was dominant for visuospatial functions. Single photon emission CT revealed a low
      perfusion area only in the right thalamus. These findings suggest that the right
      hemisphere might be dominant for both verbal and non-verbal memory function in
      this patient, although visuospatial function was lateralized in the left
      hemisphere.

PMID- 11595090
TI  - Visual imagery in hemianopic patients.
AB  - In this article we report some findings about visual imagery in patients with
      stable homonymous hemianopia compared to healthy control subjects. These findings
      were obtained by analyzing the gaze control through recording of eye movements in
      different phases of viewing and imagery. We used six different visual stimuli for
      the consecutive viewing and imagery phases. With infrared oculography, we
      recorded eye movements during this presentation phase and in three subsequent
      imagery phases in absence of the stimulus. Analyzing the basic parameters of the
      gaze sequences (known as "scanpaths"), we discovered distinct characteristics of
      the "viewing scanpaths" and the "imagery scanpaths" in both groups, which
      suggests a reduced extent of the image within the cognitive representation. We
      applied different similarity measures (string/vector string editing, Markov
      analysis). We found a "progressive consistency of imagery," shown through raising
      similarity values for the comparison of the late imagery scanpaths. This result
      suggests a strong top-down component in picture exploration: In both groups,
      healthy subjects and hemianopic patients, a mental model of the viewed picture
      must evolve very soon and substantially determine the eye movements. As our
      hemianopic patients showed analogous results to the normal subjects, we conclude
      that these patients are well adjusted to their deficit and, despite their
      perceptual defect, have a preserved cognitive representation, which follows the
      same top-down vision strategies in the process of visual imagery.

PMID- 11595091
TI  - The role of perceptual load in neglect: rejection of ipsilesional distractors is
      facilitated with higher central load.
AB  - Neglect is known to produce a bias towards the ipsilesional side. Here we
      examined whether this bias is automatic or can be modulated by manipulating
      perceptual load in a relevant task [e.g., Lavie, N. (1995). Perceptual load as a
      necessary condition for selective attention. Journal of Experimental Psychology:
      Human Perception and Performance, 21, 451-468]. Three patients with left neglect
      and three healthy controls made speeded choice responses to a target letter in
      the center of the display while attempting to ignore an irrelevant distractor
      presented on left or right. Perceptual load was manipulated by inducing a search
      for the target that appeared with another central stimulus, which was either a
      blob (low load) or a nontarget letter (higher load). Response competition effects
      from ipsilesional distractors were significantly reduced by higher load. The same
      increase of load, however, did not decrease distractor effects in the control
      group, as expected [e.g., Lavie, N., & Cox, S. (1997). On the efficiency of
      attentional selection: Efficient visual search results in inefficient rejection
      of distraction. Psychological Science, 8, 395-398]. These results demonstrate
      that ipsilesional bias in neglect is not fully automated and emphasize an
      additional restriction of perceptual capacity. Moreover, they supported our
      prediction that reduced perceptual capacity in neglect can lead to improved
      distractor rejection with just small increases in perceptual load.

PMID- 11595092
TI  - Electrophysiological correlates of the retrieval of emotional and non-emotional
      context.
AB  - In two experiments, words were presented in negatively or neutrally valenced
      sentences. At test, subjects made old/new recognition judgments to these words.
      In Experiment 2 only, for words judged old, subjects also indicated whether the
      words had been studied in a neutral or a negative context. In Experiment 1, left
      parietal old/new event-related brain potential (ERP) effects were larger and more
      sustained when elicited by words that had been studied in negative sentences, and
      a right frontal old/new effect was elicited by these words exclusively. In
      Experiment 2, the left parietal and right frontal effects elicited by old words
      correctly assigned to their study context were equivalent in size regardless of
      the nature of the context; a third ERP old/new effect, maximal over posterior
      scalp regions, was seen only for words from negative contexts. The findings
      indicate that incidental retrieval of emotional context gives rise to greater
      activation in neural systems supporting conscious recollection than does
      retrieval of nonemotional context. When contextual retrieval is intentional,
      recollection of emotional and non-emotional information are associated with
      equivalent engagement of these systems. The findings from Experiment 2 suggest
      that additional neural circuitry may be activated selectively by emotionally
      valenced episodic information.

PMID- 11595093
TI  - Longitudinal profiles of semantic impairment for living and nonliving concepts in
      dementia of Alzheimer's type.
AB  - Two types of theoretical account have been proposed to explain the phenomenon of
      category-specific impairment in tests of semantic memory: One stresses the
      importance of different cortical regions to the representation of living and
      nonliving categories, while the other emphasize the importance of statistical
      relationships among features of concepts belonging to these two broad semantic
      domains. Theories of the latter kind predict that the direction of a domain
      advantage will be determined in large part by the overall damage to the semantic
      system, and that the profiles of patients with progressive impairments of
      semantic memory are likely to include a point at which an advantage for one
      domain changes to an advantage for the other. The present series of three studies
      employed semantic test data from two separate cohorts of patients with probable
      dementia of Alzheimer's type (DAT) to look for evidence of such a crossover. In
      the first study, longitudinal test scores from a cohort of 58 patients were
      examined to confirm the presence of progressive semantic deterioration in this
      group. In the second study, Kaplan-Meier survival curves based on serial naming
      responses and plotted separately for items belonging to living and nonliving
      domains indicated that the representations of living concepts (as measured by
      naming) deteriorated at a consistently and significantly faster rate than those
      of nonliving concepts. A third study, carried out to look in detail at the
      performance of mildly affected patients, employed an additional cross-sectional
      cohort of 20 patients with mild DAT and utilized a graded naming assessment. This
      study also revealed no evidence for a crossover in the advantage of one domain
      over the other as a function of disease severity. Taken together with the model
      of anatomical progression in DAT based on the work of Braak and Braak (1991),
      these findings are interpreted as evidence for the importance of regional
      cerebral anatomy to the genesis of semantic domain effects in DAT.

PMID- 11595094
TI  - Motor and visual imagery as two complementary but neurally dissociable mental
      processes.
AB  - Recent studies indicate that covert mental activities, such as simulating a motor
      action and imagining the shape of an object, involve shared neural
      representations with actual motor performance and with visual perception,
      respectively. Here we investigate the performance, by normal individual and
      subjects with a selective impairment in either motor or visual imagery, of an
      imagery task involving a mental rotation. The task involved imagining a hand in a
      particular orientation in space and making a subsequent laterality judgement. A
      simple change in the phrasing of the imagery instructions (first-person or third
      person imagery) and in actual hand posture (holding the hands on the lap or in
      the back) had a strong impact on response time (RT) in normal subjects, and on
      response accuracy in brain-damaged subjects. The pattern of results indicates
      that the activation of covert motor and visual processes during mental imagery
      depends on both top-down and bottom-up factors, and highlights the distinct but
      complementary contribution of covert motor and visual processes during mental
      rotation.

PMID- 11595096
TI  - Synaesthetic photisms influence visual perception.
AB  - When C, a digit-color synaesthete, views black digits, she reports that each
      digit elicits a highly specific color (a photism), which is experienced as though
      the color was externally projected onto the digit. We evaluated this claim by
      assessing whether C's photisms influenced her ability to perceive visually
      presented digits. C identified and localized target digits presented against
      backgrounds that were either congruent or incongruent with the color of her
      photism for the digits. The results showed that C was poorer at identifying and
      localizing digits on congruent than incongruent trials. Such differences in
      performance between congruent and incongruent trials were not found with
      nonsynaesthete control participants. These results suggest that C's colored
      photisms influence her perception of black digits. We propose a model in which
      color information influences the perception of digits through reentrant pathways
      in the visual system.

PMID- 11595095
TI  - Ipsilesional biases in saccades but not perception after lesions of the human
      inferior parietal lobule.
AB  - We examined the effects of chronic unilateral lesions to either the inferior
      parietal lobe, or to the dorsolateral prefrontal cortex including the frontal eye
      fields (FEFs), upon human visual perception and saccades in temporal-order
      judgment (TOJ) tasks. Two visual events were presented on each trial, one in each
      hemifield at various stimulus onset asynchronies (SOAs). In the saccade task,
      patients moved their eyes to whichever stimulus attracted gaze first. In the
      perceptual-manual task, they pressed a button to indicate which stimulus was
      perceived first. Frontal patients showed appropriate TOJs for visual targets in
      both tasks. Parietal patients showed appropriate TOJs in the perceptual-manual
      but not the saccade task; their saccades tended to be ipsilesional unless the
      contralesional target led substantially. This reveals a bias in saccade choice
      after parietal damage that cannot be attributed to deficient visual perception.
      These results challenge previous claims that only anterior lesions produce
      motoric spatial biases in humans. However, they are in accord with recent
      neurophysiological evidence for parietal involvement in saccade generation, and
      also with suggestions that visuomotor transformations in the parietal lobe
      serving direct spatial motor responses can dissociate from conscious perception
      as indicated by indirect arbitrary responses.

PMID- 11595097
TI  - Structural encoding of human and schematic faces: holistic and part-based
      processes.
AB  - The range of specificity and the response properties of the extrastriate face
      area were investigated by comparing the N170 event-related potential (ERP)
      component elicited by photographs of natural faces, realistically painted
      portraits, sketches of faces, schematic faces, and by nonface meaningful and
      meaningless visual stimuli. Results showed that the N170 distinguished between
      faces and nonface stimuli when the concept of a face was clearly rendered by the
      visual stimulus, but it did not distinguish among different face types: Even a
      schematic face made from simple line fragments triggered the N170. However, in a
      second experiment, inversion seemed to have a different effect on natural faces
      in which face components were available and on the pure gestalt-based schematic
      faces: The N170 amplitude was enhanced when natural faces were presented upside
      down but reduced when schematic faces were inverted. Inversion delayed the N170
      peak latency for both natural and schematic faces. Together, these results
      suggest that early face processing in the human brain is subserved by a multiple
      component neural system in which both whole-face configurations and face parts
      are processed. The relative involvement of the two perceptual processes is
      probably determined by whether the physiognomic value of the stimuli depends upon
      holistic configuration, or whether the individual components can be associated
      with faces even when presented outside the face context.

PMID- 11595098
TI  - Changes in the human brain during rhythm learning.
AB  - Subjects were scanned with PET while they learned a complex arbitrary rhythm,
      paced by visual cues. In the comparison condition, the intervals were varied
      randomly. The behavioral results showed that the subjects decreased their
      response time with training, thus becoming more accurate in responding to the
      pacing cues at the appropriate time. There were learning-related increases in the
      posterior lateral cerebellum (lobule HVIIa), intraparietal and medial parietal
      cortex, presupplementary motor area (pre-SMA), and lateral premotor cortex.
      Learning-related decreases were found in the prestriate and inferior temporal
      cortex, suggesting that with practice the subjects increasingly came to depend on
      internal rather than external cues to time their responses. There were no
      learning-related increases in the basal ganglia. It is suggested that it is the
      neocortical-cerebellar loop that is involved in the timing and coordination of
      responses.

PMID- 11595099
TI  - Electrophysiological evidence for early contextual influences during spoken-word
      recognition: N200 versus N400 effects.
AB  - An event-related brain potential experiment was carried out to investigate the
      time course of contextual influences on spoken-word recognition. Subjects were
      presented with spoken sentences that ended with a word that was either (a)
      congruent, (b) semantically anomalous, but beginning with the same initial
      phonemes as the congruent completion, or (c) semantically anomalous beginning
      with phonemes that differed from the congruent completion. In addition to finding
      an N400 effect in the two semantically anomalous conditions, we obtained an early
      negative effect in the semantically anomalous condition where word onset differed
      from that of the congruent completions. It was concluded that the N200 effect is
      related to the lexical selection process, where word-form information resulting
      from an initial phonological analysis and content information derived from the
      context interact.

PMID- 11595100
TI  - The context of uncertainty modulates the subcortical response to predictability.
AB  - Implicit motor learning tasks typically involve comparisons of subject responses
      during a sequence versus a random condition. In neuroimaging, brain regions that
      are correlated with a sequence are described, but the temporal relationship of
      sequence versus nonsequence conditions is often not explored. We present a
      functional magnetic resonance imaging (fMRI) study describing activation related
      to sequential predictability in an implicit sensorimotor learning task and the
      history (context) dependence of these effects. Participants regarded four squares
      displayed horizontally across a screen and pressed a button when any one of the
      four targets was illuminated in a particular color. A repeating spatial sequence
      with varying levels of predictability was embedded within a random color
      presentation. Both the right dorsolateral prefrontal cortex (R DLPFC) and right
      caudate displayed a positive correlation to increasing predictability, whereas
      the left posterior parietal cortex (L PPC) displayed a negative correlation.
      However, the activation changes within the caudate were significant when
      transitioning from high predictability to low predictability but not for the
      reverse case, suggesting a sensitivity not only to predictability but to order
      effects as well. These results support the hypothesized relationship between
      basal ganglia and visuomotor sequential learning, but demonstrate the importance
      of context upon sequence learning.

PMID- 11595101
TI  - Detection of sounds in the auditory stream: event-related fMRI evidence for
      differential activation to speech and nonspeech.
AB  - The detection of speech in an auditory stream is a requisite first step in
      processing spoken language. In this study, we used event-related fMRI to
      investigate the neural substrates mediating detection of speech compared with
      that of nonspeech auditory stimuli. Unlike previous studies addressing this
      issue, we contrasted speech with nonspeech analogues that were matched along key
      temporal and spectral dimensions. In an oddball detection task, listeners heard
      nonsense speech sounds, matched sine wave analogues (complex nonspeech), or
      single tones (simple nonspeech). Speech stimuli elicited significantly greater
      activation than both complex and simple nonspeech stimuli in classic receptive
      language areas, namely the middle temporal gyri bilaterally and in a locus
      lateralized to the left posterior superior temporal gyrus. In addition, speech
      activated a small cluster of the right inferior frontal gyrus. The activation of
      these areas in a simple detection task, which requires neither identification nor
      linguistic analysis, suggests they play a fundamental role in speech processing.

PMID- 11595102
TI  - Dissociating the neural mechanisms of visual attention in change detection using
      functional MRI.
AB  - We investigated using functional magnetic resonance imaging (fMRI) the neural
      processes associated with performance of a change-detection task. In this task,
      two versions of the same picture are presented in alternation, separated by a
      brief mask interval. Even when the two pictures greatly differ (e.g., as when a
      building is in different locations), subjects report that identification of the
      change is difficult and often take 30 or more seconds to identify the change.
      This phenomenon of "change blindness" provides a powerful and novel paradigm for
      segregating components of visual attention using fMRI that can otherwise be
      confounded in short-duration tasks. By using a response-contingent event-related
      analysis technique, we successfully dissociated brain regions associated with
      different processing components of a visual change-detection task. Activation in
      the calcarine cortex was associated with task onset, but did not vary with the
      duration of visual search. In contrast, the pattern of activation in dorsal and
      ventral visual areas was temporally associated with the duration of visual
      search. As such, our results support a distinction between brain regions whose
      activation is modulated by attentional demands of the visual task (extrastriate
      cortex) and those that are not affected by it (primary visual cortex). A second
      network of areas including central sulcus, insular, and inferior frontal cortical
      areas, along with the thalamus and basal ganglia, showed phasic activation tied
      to the execution of responses. Finally, parietal and frontal regions showed
      systematic deactivations during task performance, consistent with previous
      reports that these regions may be associated with nontask semantic processing. We
      conclude that detection of change, when transient visual cues are not present,
      requires activation of extrastriate visual regions and frontal regions
      responsible for eye movements. These results suggest that studies of change
      blindness can inform understanding of more general attentional processing.

PMID- 11595103
TI  - How does the brain discriminate familiar and unfamiliar faces?: a PET study of
      face categorical perception.
AB  - Where and how does the brain discriminate familiar and unfamiliar faces? This
      question has not been answered yet by neuroimaging studies partly because
      different tasks were performed on familiar and unfamiliar faces, or because
      familiar faces were associated with semantic and lexical information. Here eight
      subjects were trained during 3 days with a set of 30 faces. The familiarized
      faces were morphed with unfamiliar faces. Presented with continua of unfamiliar
      and familiar faces in a pilot experiment, a group of eight subjects presented a
      categorical perception of face familiarity: there was a sharp boundary in
      percentage of familiarity decisions between 40% and 60% faces. In the main
      experiment, subjects were scanned (PET) on the fourth day (after 3 days of
      training) in six conditions, all requiring a sex classification task. Completely
      novel faces (0%) were presented in Condition 1 and familiar faces (100%) in
      Condition 6, while faces of steps of 20% in the continuum of familiarity were
      presented in Conditions 2 to 5 (20% to 80%). A principal component analysis (PCA)
      indicated that most variations in neural responses were related to the
      dissociation between faces perceived as familiar (60% to 100%) and faces
      perceived as unfamiliar (0 to 40%). Subtraction analyses did not disclose any
      increase of activation for faces perceived as familiar while there were large
      relative increases for faces perceived as unfamiliar in several regions of the
      right occipito-temporal visual pathway. These changes were all categorical and
      were observed mainly in the right middle occipital gyrus, the right posterior
      fusiform gyrus, and the right inferotemporal cortex. These results show that (1)
      the discrimination between familiar and unfamiliar faces is related to relative
      increases in the right ventral pathway to unfamiliar/novel faces; (2) familiar
      and unfamiliar faces are discriminated in an all-or-none fashion rather than
      proportionally to their resemblance to stored representations; and (3)
      categorical perception of faces is associated with abrupt changes of brain
      activity in the regions that discriminate the two extremes of the
      multidimensional continuum.

PMID- 11595112
TI  - Targeting signal transduction.

PMID- 11595113
TI  - Brain metastases: still an 'orphan' disease?
AB  - The diagnosis of brain metastases from systemic cancer has been associated with a
      poor prognosis. In fact, most chemotherapy clinical trials exclude patients with
      metastatic disease. In the past, clinical and basic research activity in this
      area has been only moderate. Recent developments in clinical trial design, as
      evidenced by recursive partitioning analysis and complemented by new treatment
      strategies in neurosurgery and radiotherapy, suggest a change in attitude and
      approach to the management of brain metastases. The role of chemotherapy will
      require more focused investigation, but recent advances in our understanding of
      the biology of brain metastases suggest that the next generation of chemotherapy
      treatments will involve targeting specific pathways of metastatic disease.

PMID- 11595114
TI  - Brain metastases: biology and the role of the brain microenvironment.
AB  - Metastatic lesions constitute the most frequently occurring malignancy in the
      brain, and their detection portends a grim prognosis. Efforts to treat these
      lesions have failed partly because the biologic processes that govern their
      development are poorly understood. In recent years, it has become evident that
      metastases occur as a result of a multistep process involving a rigorous natural
      selection of cells in the primary tumor that bear molecular and biologic
      characteristics permitting brain metastasis. In addition, recent studies have
      uncovered the importance of the brain microenvironment and its contribution to
      the metastatic process. The development of targeted therapies against brain
      metastases demands a better understanding of these molecular processes and the
      factors that influence them. This review examines the interplay between tumor
      cells and host brain tissue in the context of our current understanding of the
      role of various molecules involved in the metastatic process.

PMID- 11595115
TI  - Surgical management of brain metastases.
AB  - Metastatic brain tumors are the most common intracranial tumors in adults and the
      most common cause of neurologic morbidity and mortality in these patients. Recent
      advances in the management of the primary cancer have resulted in improved
      prognosis, longer survival, and thus, increased identification of the presence of
      brain metastases. Data suggest that aggressive treatment of the metastatic brain
      tumor with surgical resection increases the length of survival in these patients.
      New techniques, including preoperative functional imaging, stereotactic surgical
      resection, image-guided neurosurgery, intraoperative ultrasound, and cortical
      mapping, have aided neurosurgeons in surgical resection and have helped to lower
      the associated surgical morbidity and mortality. The respective roles of surgery,
      patient selection, prognostic factors, and radiotherapy are addressed in this
      review.

PMID- 11595116
TI  - Radiotherapy and radiosurgical management of brain metastases.
AB  - Out of the various cancer treatment modalities available, radiotherapy is the
      most commonly used for managing metastatic disease in the brain. Until recent
      years, this was almost exclusively limited to whole-brain radiotherapy (WBRT).
      Radiosurgery has emerged as a powerful technique for controlling small to
      moderate-sized brain metastases (<4 cm in diameter). Tumor control rates with
      radiosurgery are superior to those with WBRT and appear to equal or surpass those
      with surgery plus WBRT in most studies. The choice among various radiation
      management strategies (radiosurgery alone, radiosurgery plus WBRT, or surgery
      followed by radiotherapy) should be based on the size and location of the brain
      metastases, the functional and neurologic status of the patient, the type of
      tumor, the tumor imaging characteristics, and the patient's concerns about the
      risks and side effects of the proposed treatment.

PMID- 11595117
TI  - Chemotherapy for metastatic tumors to the central nervous system.
AB  - Management of patients with central nervous system metastases poses numerous
      challenges. This review focuses on the use of chemotherapy in these patients,
      addressing treatment difficulties such as drug resistance and possible solutions.
      The impact of the blood-brain barrier is considered less of a limitation than
      once thought. The advent of targeted signal transduction inhibitors is noted in
      this context. The current efficacy of chemotherapeutic agents and combinations is
      also discussed, with results from large studies highlighting a positive survival
      trend for chemotherapy in selected tumor histologies.

PMID- 11595118
TI  - Postmastectomy radiotherapy in women with breast cancer metastatic to one to
      three axillary lymph nodes.
AB  - The influence of postmastectomy radiotherapy on survival has long been debated.
      Early randomized trials established a clear role for adjuvant postmastectomy
      chest wall radiotherapy (PMCWRT) in reducing locoregional recurrence (LRR), and
      PMCWRT became standard therapy for patients at high risk of LRR: those with T3 or
      T4 tumors and four or more involved lymph nodes. However, without effective
      systemic therapy, distant metastases limited any effect of improved local control
      on overall outcome, and radiotherapy showed no benefit in survival. In fact,
      early meta-analyses showed a negative impact of radiotherapy on survival. As data
      and techniques matured, a favorable influence of PMCWRT on breast cancer-specific
      mortality emerged but was offset by a radiotherapy-related increase in vascular
      mortality. Improvements in radiotherapy delivery to increase efficacy and reduce
      toxicity, restriction of PMCWRT to patients at intermediate or high risk of LRR
      after mastectomy, and improved distant control of disease with systemic therapy
      are expected to bring the greatest likelihood of a survival advantage from
      locoregional control. Three randomized trials with sufficient follow-up meet
      these criteria. All demonstrate significant improvement in overall survival with
      PMCWRT. However, the trials were not designed to specifically address the benefit
      of PMCWRT in patients at intermediate risk of LRR (those with T1 or T2 tumors and
      one to three involved lymph nodes). These findings have been discussed in a host
      of publications and conferences in light of historical negative results. This
      review focuses on the recent data on PMCWRT in patients with one to three
      involved nodes.

PMID- 11595119
TI  - The role of bisphosphonates as adjuvant therapy for breast cancer.
AB  - Bone is the most common site of distant recurrence in breast cancer. The
      development of skeletal metastases involves complex interactions between the
      cancer cells and the bone microenvironment. The presence of tumor in bone is
      associated with activation of osteoclasts, resulting in excessive bone
      resorption. Bisphosphonates are potent inhibitors of osteoclastic bone resorption
      with proven efficacy in reducing tumor-associated skeletal complications. Several
      studies have investigated the adjuvant, or preventive, use of these drugs in
      breast cancer. Laboratory experiments have shown that the development of bone
      metastases can be inhibited by bisphosphonates. Three randomized clinical trials
      of bisphosphonates in nonmetastatic breast cancer patients have yielded
      conflicting results with respect to development of osseous and visceral
      metastases and survival. Defining the potential role of these agents in adjuvant
      breast cancer treatment requires further investigation in randomized, large
      scale, multicenter clinical trials. The data available to date provide a strong
      impetus for continued clinical and laboratory work with bisphosphonates in breast
      cancer.

PMID- 11595120
TI  - The role of adjuvant monoclonal antibody therapy for breast cancer: rationale and
      new studies.
AB  - HER2 is a member of the epidermal growth factor receptor (EGFR) family of
      tyrosine kinases and is involved in the growth, invasion, metastasis, and
      prognosis of breast cancer. The rationale for prospective trials evaluating the
      role of anti-HER2 monoclonal antibody therapy for patients with high-risk HER2
      positive resected breast cancer is based on several factors. These include 1) the
      relative and absolute poor prognosis of patients with node-positive, HER2
      positive breast cancer; 2) the emerging data of potential importance concerning
      anthracyclines as a component of adjuvant therapy for patients with HER2-positive
      breast cancer; 3) the role of taxanes in the management of patients with HER2
      positive metastatic breast cancer; and 4) the feasibility and efficacy of
      molecularly targeted anti-HER2 monoclonal antibody treatment alone or in
      combination with chemotherapy for patients with advanced breast cancer.

PMID- 11595121
TI  - What is the ideal duration of adjuvant therapy for primary breast cancer: are
      four cycles of cyclophosphamide and doxorubicin enough?
AB  - For 25 years we have known that adjuvant chemotherapy improves both disease-free
      and overall survival for many of our patients with primary breast cancer. We also
      know that these therapies have significant toxicities and are not always
      effective. We have therefore focused a great deal of effort into maximizing the
      effectiveness of adjuvant chemotherapy and defining just how much chemotherapy,
      with respect to both dose and duration, is necessary to achieve this maximum
      benefit. In our attempt to define these parameters through clinical trials, we
      have been faced with many options, and we may not yet have defined an optimal
      regimen of chemotherapy, or an optimal duration. Although many physicians in the
      United States consider four cycles of cyclophosphamide and doxorubicin as
      "standard of care" for patients with primary breast cancer, many feel that both
      choice of regimen and duration of treatment remain controversial. The reasons for
      this uncertainty and lack of clarity are complex, and they are addressed in this
      review.

PMID- 11595122
TI  - Adjuvant chemotherapy for tumors of one centimeter or less: the law of
      diminishing returns.
AB  - The role of adjuvant chemotherapy in treatment of breast cancers of 1 cm or less
      is controversial. Careful consideration must be given to the overall risk of
      recurrence and death and to the absolute benefit of adjuvant chemotherapy, given
      that risk. Studies in this group of patients indicate that their overall survival
      rate is 90% to 99%. The absolute benefit of chemotherapy in this setting is most
      likely 1% or less. Adjuvant chemotherapy has significant toxicities, including
      cognitive dysfunction, early menopause, leukemia, and even death. Following a
      realistic and detailed discussion between patient and oncologist, some patients
      may choose chemotherapy. However, for the majority of patients with breast
      cancers of 1 cm or less, the minimal benefit of adjuvant chemotherapy does not
      justify the risk of the treatment.

PMID- 11595123
TI  - Effect of soy isoflavone supplementation on markers of oxidative stress in men
      and women.
AB  - Dietary intake of soy has been linked with decreased cancer risk, and the active
      compounds in soy that have been identified include the isoflavones genistein and
      daidzein. Since these compounds have antioxidant properties, we examined levels
      of oxidative damage in blood of six women and six men before and during soy
      supplementation using Novasoy tablets. Blood samples were obtained at weekly
      intervals for 3 weeks from the women taking 50-mg isoflavones once daily and the
      men taking 50-mg isoflavones twice daily. Plasma levels of genistein and daidzein
      increased after supplementation with maximal levels occurring at 2 weeks for the
      women while levels in men kept increasing over the 3 weeks of study. There was
      wide variation between individuals in the levels of isoflavones achieved. Mean
      levels of 5-hydroxymethyl-2'-deoxyuridine (5-OHmdU) in DNA from nucleated blood
      cells decreased after 1 week of supplementation in the women, with a decrease of
      47% in mean 5-OHmdU levels after 3 weeks. In men, mean 5-OHmdU levels did not
      decrease until after 3 weeks of supplementation, at which there was 61% decrease.
      Mean plasma levels of 8-isoprostanes were not changed appreciably in either men
      or women. These pilot results suggest that soy isoflavone supplementation
      decreases levels of oxidative DNA damage in humans, and this may be a mechanism
      behind the cancer-preventive effects of soy isoflavones.

PMID- 11595124
TI  - Exogenous expression of p21(WAF1/CIP1) exerts cell growth inhibition and enhances
      sensitivity to cisplatin in hepatoma cells.
AB  - The effects of exogenous expression of p21(WAF1/CIP1) in hepatoma cells were
      examined. Two stably p21(WAF1/CIP1)-transfected clones and one clone transfected
      with expression vector only were used for study. Introduction of p21(WAF1/CIP1)
      resulted in significant cell growth inhibition, and the magnitude of the cell
      growth inhibition in these transfected cells was proportional to the level of
      p21(WAF1/CIP1) protein expressed. Exogenous p21(WAF1/CIP1) expression also
      significantly enhanced chemosensitivity to cisplatin. In addition, apoptosis
      occurred earlier in cells transfected with p21(WAF1/CIP1) after cisplatin
      treatment. These findings raise the potential that forced upregulation of
      p21(WAF1/CIP1) in hepatocellular carcinoma (HCC) may reduce the doses of
      cisplatin to achieve similar responses and suggest the possible use of
      p21(WAF1/CIP1) in HCC treatment.

PMID- 11595125
TI  - Sequence-dependent antitumor efficacy of combination chemotherapy with
      nedaplatin, a newly developed platinum, and paclitaxel.
AB  - We evaluated the sequence dependency of antitumor efficacy and toxicity in
      combination therapy of nedaplatin (NDP) with paclitaxel (TXL) against Lewis lung
      carcinoma. The sequential administration of NDP prior to TXL (NT therapy)
      resulted in severe body weight loss followed by frequent toxic death of mice. In
      contrast, the sequential dosing of TXL prior to NDP (TN therapy) resulted in
      synergistically enhanced inhibition of tumor growth with less toxicity compared
      with the NT therapy. Comparing the antitumor activity of NDP plus TXL with that
      of cisplatin (CDDP) plus TXL or carboplatin (CBDCA) plus TXL, the combination
      effect of NDP plus TXL was significantly higher than that of CDDP plus TXL or
      CBDCA plus TXL. These results indicate that the TN therapy may have significant
      potential in clinical use.

PMID- 11595126
TI  - Newcastle disease virus therapy of human tumor xenografts: antitumor effects of
      local or systemic administration.
AB  - Previously we showed that a single local injection of the avian paramyxovirus
      Newcastle disease virus (NDV) strain 73-T caused long-lasting, complete tumor
      regression of human neuroblastoma and fibrosarcoma xenografts in athymic mice.
      Here we report the antitumor effects of NDV administered by either the
      intratumoral (IT) route to treat a variety of human carcinoma xenografts or by
      the systemic (intraperitoneal, IP) route to treat neuroblastoma xenografts (6.5
      12 mm in diameter). For IT treatments, mice were randomized into treatment groups
      and given a single IT injection of NDV 73-T, vehicle (phosphate buffered saline,
      PBS), or UV-inactivated NDV. For systemic therapy, mice (n=18) with subcutaneous
      IMR-32 human neuroblastoma xenografts received IP injections of NDV (5 x 10(9)
      PFU). Significant tumor growth inhibition (77-96%) was seen for epidermoid (KB8-5
      11), colon (SW620 and HT29), large cell lung (NCIH460), breast (SKBR3), prostate
      (PC3), and low passage colon (MM17387) carcinoma xenografts treated IT with NDV.
      In all cases, tumors treated IT with PBS or replication-incompetent, UV
      inactivated NDV displayed rapid tumor growth. After a single IP injection of NDV,
      complete regression of IMR-32 neuroblastomas was observed in 9 of 12 mice without
      recurrence for the 3-9 month follow-up period. Six mice with recurrent
      neuroblastomas after one IP injection received one to three additional IP
      treatments with NDV. Three of these six mice showed complete regression without
      recurrence. These data show that: (1) NDV administered either IT or IP is an
      effective antitumor therapy in this system, (2) replication competency is
      necessary for maximal effect, and (3) multiple NDV doses can be more effective
      than a single dose. These studies provide further rationale for the preclinical
      study of NDV as an oncolytic agent.

PMID- 11595127
TI  - Serum level of the periostin, a homologue of an insect cell adhesion molecule, in
      thymoma patients.
AB  - Periostin protein shares structural and sequence homology with fasciclin I, which
      is an insect adhesion molecule. Periostin has a typical signal peptide at the N
      terminal end suggesting it is a secreted protein. Recently, we developed a novel
      sandwich chemiluminescence assay to determine serum concentrations of periostin.
      We investigated the serum periostin level in thymoma patients, and attempted to
      determine the correlation between serum periostin level and clinicopathological
      factors of thymoma patients who had undergone surgery between January 1994 and
      July 1996. Serum periostin levels were not significantly different between the
      thymoma patients (1264.4+/-122.9 ng/ml) and the normal control (962.0+/-118.6
      ng/ml) (P=0.0877). There was no relationship between serum periostin level and
      age, gender or pathological subtype. However the serum periostin level of stage
      IV patients (1497.0+/-285.8 ng/ml) was significantly higher than normal control
      (P=0.0460). These data suggest that serum periostin level may indicate tumor
      invasion and progression of thymoma.

PMID- 11595129
TI  - A comparison between microsatellite analysis and cytology of urine for the
      detection of bladder cancer.
AB  - We have studied, in a blinded fashion, cytology and microsatellite analysis on
      urine sediments of 143 Chinese with or without bladder lesions. Microsatellite
      analysis succeeded in all 143 individuals, while cytology could not be performed
      on 42 subjects due to insufficient urine samples. Both microsatellite analysis
      and routine urine cytology succeeded in 81 bladder cancer patients. Seventy-three
      patients (90%) were identified by microsatellite analysis, while only 41 patients
      (51%) were identified by cytology. However, four patients were identified by
      routine cytology but not by microsatellite analysis. Our results proved that
      microsatellite analysis is more sensitive than routine cytology but the two
      methods are complementary to each other.

PMID- 11595128
TI  - A role for protein kinase C delta in the differential sensitivity of MCF-7 and
      MDA-MB 231 human breast cancer cells to phorbol ester-induced growth arrest and
      p21(WAFI/CIP1) induction.
AB  - The goal of this study was to investigate the differential sensitivity of
      estrogen receptor (ER) positive MCF-7 and ER negative MDA-MB 231 breast cancer
      cells to phorbol myristate acetate (PMA)-dependent growth arrest. MCF-7 cells
      were growth arrested by 80% while MDA-MB 231 cells were arrested by 20% in
      response to seven days of treatment with 10 nM PMA. Coincident with the increased
      sensitivity of MCF-7 cells to be growth arrested by the protein kinase C (PKC)
      activator PMA, PMA induced 9-fold higher levels of the cyclin dependent kinase
      (Cdk) inhibitor p21(WAF1/GIP1) in MCF-7 compared to MDA-MB 231 cells. A
      comparison of the PKC isoforms expressed in MCF-7 versus MDA-MB 231 cells showed
      that only the PMA-sensitive PKC delta and eta isoforms were expressed at markedly
      (> or =10-fold) elevated levels in MCF7 versus MDA-MB 231 cells. These results
      suggested that the differential sensitivity to growth arrest and induction of
      p2l(WAFl/CIPl) could reflect, at least in part, increased expression of PMA
      dependent PKC isoforms delta and/or eta. Direct evidence to support this
      hypothesis was provided by the ability of transient transfections into MCF-7
      cells of constitutively active PKC delta but not of PKC's eta or alpha or epsilon
      to enhance p21(WAFl/CIP1) promoter activity. These results suggest that PKC delta
      plays a fundamental role in the regulation of growth in estrogen receptor
      positive breast cancer cells.

PMID- 11595130
TI  - Alterations at the Ink4a locus in transplacentally induced murine lung tumors.
AB  - The malignant phenotype results from multiple genetic alterations, including the
      activation of oncogenes and inactivation of tumor suppressor genes. Activation of
      the Ki-ras oncogene has been implicated as an early event in the pathogenesis of
      lung adenocarcinomas in humans and experimental animal models. Previous studies
      from this laboratory have shown that, following treatment of pregnant [D2 x
      B6D2F(1)]F(2) or Balb/c mice with the polycyclic aromatic hydrocarbon, 3
      methylcholanthrene (MC), lung tumors from the transplacentally exposed offspring
      exhibited a high incidence of mutations in the Ki-ras gene. The role of genetic
      alterations at other oncogenic or tumor suppressor loci that can mediate lung
      tumor initiation and/or progression have not been well characterized in either
      human or murine models. Using the transplacental carcinogenesis model, which
      results in the induction of both lung and liver tumors following in utero
      exposure to MC, the results of this and our previous studies show that
      alterations in the Ink4a locus occur in only 15 and 27% of the lung and liver
      tumors, respectively. Preliminary data also suggests that the type of mutation
      induced in the Ki-ras gene following the initial exposure to MC may influence
      lung tumor progression. These results imply that damage to the Ink4a gene is not
      a frequent pathway to malignant progression in mouse lung and liver tumors
      following in utero exposure to environmental carcinogens.

PMID- 11595131
TI  - Significant overexpression of oligophrenin-1 in colorectal tumors detected by
      cDNA microarray analysis.
AB  - The human oligophrenin-1 gene is ubiquitously expressed at low levels and
      expressed at high levels in the developing neuroepithelium of the neural tube.
      Mutations in this gene have been related to the X-linked mental retardation.
      Using cDNA microarrays, we found evidence that oligophrenin-1 is strongly up
      regulated in colorectal tumors. Semiquantitative reverse transcriptase polymerase
      chain reaction confirmed this finding. Thus, a well-known nervous system
      associated human gene transcript may also be an important colorectal tumor marker
      and potential therapeutic target.

PMID- 11595132
TI  - Immunohistochemical analysis of pro-apoptotic Bid level in chronic hepatitis,
      hepatocellular carcinoma and liver metastases.
AB  - Bid, a member of the Bcl-2 family, mediates apoptosis by inducing the release of
      proapoptotic factors. The expression of Bid in liver diseases has not been
      investigated. This study evaluated Bid level in various liver diseases including
      hepatocellular carcinoma (HCC), liver metastases from colorectal cancer, chronic
      hepatitis and liver cirrhosis. The expression of Bid in tumorous tissues of HCC
      was lower than that in their corresponding non-tumorous tissues from the same
      patient. Heavy staining with Bid antibody was found in some localized tumorous
      liver tissues from patients with poorly differentiated tumors. In patients with
      chronic hepatitis and liver cirrhosis, there were gradient tumor-development
      centers, a gradient increase in reaction with Bid antibody from the middle of the
      center to its edge. The gradient tumor-development center was also found in non
      tumorous tissues of HCC, suggesting that occurrence of this center in chronic
      hepatitis might be an early pathologic sign of HCC development. Bid was also
      expressed in the epithelial cells in tissues from liver metastases and their
      expression was often stronger than in the non-tumorous liver tissues. Heavy
      nuclear staining of Bid was not uncommon in these metastatic cells. The different
      patterns of staining between primary and secondary liver tumors may reflect a
      difference in tumor origin and in cell type. Nuclei of metastatic cells, though
      positive for Bid, still showed a considerable mitotic activity, indicating that
      they were in active proliferation rather than on a pathway deemed to be
      apoptotic. In conclusion, this study shows that the Bid level is decreased in HCC
      except in poorly differentiated HCC in which cells may undergo a process of
      apoptosis or necrosis. The existence of gradient tumor-development center in
      chronic hepatitis, liver cirrhosis and non-tumorous tissues from HCC may serve as
      a pathologic marker of a carcinogenic change of cell phenotypes.

PMID- 11595133
TI  - Suppression of tumorigenicity and metastasis in B16F10 cells by PTEN/MMAC1/TEP1
      gene.
AB  - PTEN/MMAC1/TEP1 (PTEN) is a tumor suppressor gene that is mutated in a variety of
      advanced and metastatic cancers, strongly suggests that PTEN alteration is
      possibly involved in the tumor progression and formation of metastases. However,
      the roles of PTEN in tumor growth and metastasis and its functional mechanisms
      are not fully understood. We evaluated the tumor suppressor function of PTEN gene
      on tumor growth and metastasis in vitro and in vivo. Our results of in vitro soft
      agar assay and in vivo PTEN-expressing tumor cell growth showed that PTEN
      inhibited the tumorigenicity of B16F10 melanoma cells. Anti-metastatic function
      of PTEN was also revealed by experimental pulmonary metastatic animal model. For
      the further insight into the mechanisms underlying the PTEN-mediated inhibition
      of tumor metastasis, we have examined the role of PTEN on the secretion of matrix
      metalloproteinases (MMPs), insulin-like growth factors (IGFs) and the expression
      of secretory and cellular vascular endothelial growth factor (VEGF) proteins that
      have been described to contribute to the metastasis of tumor. PTEN significantly
      lowered MMPs and IGFs secretion and also expression of secretory and cellular
      VEGF proteins. These results suggest that PTEN tumor suppressor protein inhibits
      tumorigenicity and metastasis through regulation of MMP, IGFs, and VEGF
      expression.

PMID- 11595134
TI  - Aberrant expression of p21(WAF1/CIP1) and p27(KIP1) in cervical carcinoma.
AB  - An immuno-histochemical study of p21 and p27 expression in cervical carcinoma was
      performed in 73 patients. Positive p21 and p27 staining was detected in 35.6 and
      11% of tumour tissues, respectively. p21 expression was significantly correlated
      with advanced disease stage and negative human papilloma virus infection whilst
      positive p27 staining was not correlated with any clinical and pathological
      parameters studied. Kaplan-Meier estimation indicated that survival might be
      related to disease stage, tumour grade and p21 expression. Cox regression
      analysis confirmed that advanced stage disease and poorly differentiated tumour
      are independent prognostic factors for cervical carcinoma.

PMID- 11595135
TI  - Transcranial magnetic stimulation coregistered with MRI: a comparison of a guided
      versus blind stimulation technique and its effect on evoked compound muscle
      action potentials.
AB  - INTRODUCTION AND METHODS: Compound muscle action potentials (CMAPs) elicited by
      transcranial magnetic stimulation (TMS) are characterized by enormous
      variability, even when attempts are made to stimulate the same scalp location.
      This report describes the results of a comparison of the spatial errors in coil
      placement and resulting CMAP characteristics using a guided and blind TMS
      stimulation technique. The former uses a coregistration system, which displays
      the intersection of the peak TMS induced electric field with the cortical
      surface. The latter consists of the conventional placement of the TMS coil on the
      optimal scalp position for activation of the first dorsal interossei (FDI)
      muscle. RESULTS: Guided stimulation resulted in significantly improved spatial
      precision for exciting the corticospinal projection to the FDI compared to blind
      stimulation. This improved precision of coil placement was associated with a
      significantly increased probability of eliciting FDI responses. Although these
      responses tended to have larger amplitudes and areas, the coefficient of
      variation between guided and blind stimulation induced CMAPs did not
      significantly differ. CONCLUSION: The results of this study demonstrate that
      guided stimulation improves the ability to precisely revisit previously
      stimulated cortical loci as well as increasing the probability of eliciting TMS
      induced CMAPs. Response variability, however, is due to factors other than coil
      placement.

PMID- 11595137
TI  - Cortical myoclonus in Janz syndrome.
AB  - OBJECTIVE: To evaluate the characteristics of EEG paroxysms and the relationship
      between EEG spikes and ictal myoclonic jerks in patients with juvenile myoclonic
      epilepsy (JME). METHODS: Six patients with a typical form of JME entered the
      study and underwent computerized polygraphic recordings. In each patient, the
      inter-peak spike interval was measured on repeated EEG bursts, and jerk-locked
      back averaging was performed on ictal epochs using a time window including the
      100 ms before and the 100-200 ms after the point at which the jerk-related EMG
      potential diverged from baseline. RESULTS: In all cases, the myoclonic jerks were
      associated with polyspike waves (PSW) complexes. The frequency of repeated spikes
      within the PSW complex ranged from 16 to 27 Hz. Jerk-locked averaging revealed a
      positive-negative EEG transient with maximal amplitude on the frontal leads,
      which preceded the myoclonic jerk by 10.25+/-0.96 ms. A delay of 9.50+/-1.73 ms
      was measured between the jerk-locked positive peak detected on the frontal EEG
      leads of the two hemispheres; a comparable time lag was observed between the
      onset of myoclonic jerks in the two deltoid muscles. CONCLUSIONS: Our data
      suggest that the ultimate mechanism responsible for ictal myoclonic jerks in JME
      is largely similar to that sustaining cortical myoclonus in more severe
      pathological conditions such as progressive myoclonus epilepsies, despite the
      different pathogenic substrate and triggering mechanisms.

PMID- 11595136
TI  - Precision grip deficits in cerebellar disorders in man.
AB  - OBJECTIVE: To investigate the effect of a variety of cerebellar pathologies on a
      functional motor task (lifting an object in a precision grip). METHODS: The study
      involved 8 patients with unilateral damage in the region of the posterior
      inferior cerebellar artery (PICA), 6 with damage in the region of the superior
      cerebellar artery (SUPCA), 12 patients with familiar or idiopathic cortical
      cerebellar degeneration, and 45 age-matched normal subjects. Subjects lifted an
      object of unpredictable load (internally guided task) or responded to a sudden
      load increase while holding the object steadily (externally guided task).
      RESULTS: Damage to the dentate nucleus (SUPCA) or its afferent input (cerebellar
      atrophy) resulted in disruption of the close coordination normally seen between
      proximal muscles (lifting the object) and the fingers (gripping the object)
      during a self-paced lift. Both the SUPCA group and, more markedly, the atrophy
      group, showed exaggerated levels of grip force. All patients showed a normal rate
      of grip force development. Damage in the PICA region had no significant effect on
      any of the measured lifting parameters. All patient groups retained the ability
      to scale grip force to different object loads. The automatic grip force response
      to unexpected load increase of a hand held object showed normal latency and time
      course in all patient groups. The response was modulated by the rate of the load
      change. Response magnitude was exaggerated in the atrophy patients at all 3 rates
      tested. CONCLUSIONS: Disturbances associated with cerebellar disorders differed
      from those seen following damage to the basal ganglia, with no evidence of slowed
      rates of grip force development. Disruption of temporal coordination between the
      proximal muscles (lifting) and the fingers (gripping) in a lift was apparent,
      supporting the role of the cerebellum in coordinating the timing of multi-joint
      movement sequences. Exaggeration of grip force levels was found in association
      with damage to the dentate nucleus or, in particular, to its afferent input. This
      could support a role or the cerebellum in sensorimotor processing, but might also
      represent a failure to time correctly the duration of grip force generation.

PMID- 11595138
TI  - Inhibitory conditioning stimulus in transcranial magnetic stimulation reduces the
      number of excited spinal motor neurons.
AB  - OBJECTIVE: To study the mechanisms of amplitude attenuation caused by a
      transcranial magnetic conditioning stimulus. Both conventional MEPs and the
      recently described triple stimulation technique (TST) were applied; the latter to
      improve the quantification of the response size decrease. METHODS: TST uses a
      peripheral collision method to eliminate the effects of desynchronization of the
      transcranial magnetic stimulation (TMS) induced spinal motor neuron discharges.
      The attenuation of motor evoked potentials (MEPs) and responses to TST was
      studied in 10 healthy volunteers using the conditioning-test paradigm with 2 ms
      interstimulus intervals. RESULTS: Conventional MEPs and responses to TST
      demonstrated a marked attenuation by the preceding conditioning stimulus in all
      subjects. The ratio of MEP to TST amplitudes was the same in conditioned and
      unconditioned responses. CONCLUSIONS: Our findings suggest that the transcranial
      conditioning stimulus does not change the degrees of desynchronization of spinal
      motor neuron discharges, but results in a reduced number of excited alpha motor
      neurons. This reduction can be estimated by both MEPs and TST.

PMID- 11595139
TI  - Relation between changes in long-latency stretch reflexes and muscle stiffness in
      Parkinson's disease--comparison before and after unilateral pallidotomy.
AB  - OBJECTIVE: To study the effects of posteroventral pallidotomy on both the size of
      long-latency stretch reflex (LLR) and the muscle stiffness in the wrist flexor
      muscles. PATIENTS AND METHODS: Eleven consecutive patients (right-handed, 6 men
      and 5 women) underwent left-side microelectrode-guided pallidotomy. The LLR of
      the contralesional forearm was studied at baseline and 2-3 months after surgery
      while patients continued to take their optimal medical regimens ('on' period).
      Patients were instructed not to respond to the perturbation (passive mode) or to
      oppose the mechanical extensor perturbation (active mode). RESULTS: The stretch
      reflex evoked by extension perturbations of the wrist consisted of a short
      latency reflex (M1) and an LLR (M2). Pallidotomy had no effects on the size of M1
      components in both passive and active mode and on that of M2 component in the
      passive mode, however, it significantly reduced M2 component in the active mode
      (P<0.05). The inherent muscle stiffness over 60 ms period of mechanical stretch
      was not influenced by pallidotomy in any experimental condition (preoperative vs.
      postoperative or passive mode vs. active mode). The hand displacement following
      M2 component increased significantly after pallidotomy in both passive (P<0.005)
      and active mode (P<0.05). The inverted value of the displacement following M2
      component correlated with the size of M2 component (r=0.60, P<0.001).
      CONCLUSIONS: Pallidotomy decreased the transcortical reflex gain, probably at
      cortical level, and consequently reduced muscle stiffness.

PMID- 11595140
TI  - Differential modulation of motor evoked potential and silent period by activation
      of intracortical inhibitory circuits.
AB  - OBJECTIVES: To investigate the effect of activation of intracortical inhibitory
      circuits, as tested by short interval (3 ms) paired-pulse transcranial magnetic
      stimulation (TMS) with a conditioning-test paradigm, on the electromyographic
      (EMG) pause (silent period, SP) following the motor evoked potential (MEP) in
      normal subjects. METHODS: SPs and MEPs were recorded from the right first dorsal
      interosseous (FDI) muscle during a tonic voluntary contraction (from 70 to 90% of
      the maximum). Using a focal coil, we compared the SP duration after single-pulse
      TMS, paired-pulse TMS and single-pulse TMS of reduced intensity such as to evoke
      MEPs matched in size to the conditioned ones after paired-pulse TMS. In addition,
      we compared in a control experiment the duration of the SP following matched size
      MEPs evoked, respectively, by focal TMS with preferential activation of indirect
      I1- or I3-waves. RESULTS: SP duration after paired-pulse TMS was significantly
      longer than after single-pulse TMS evoking MEPs of a similar size. In no case the
      SP duration was longer when focal TMS preferentially activated I1-waves.
      CONCLUSIONS: The conditioning sub-threshold stimulus is more powerful in reducing
      the MEP size than in cutting down the subsequent EMG silence, suggesting that the
      neural circuits underlying MEP and SP are, at least in part, different.

PMID- 11595141
TI  - Head extensor reflex evoked by trigeminal stimulation in humans.
AB  - OBJECTIVE: Excitatory and inhibitory responses have been recognized in human
      cervical muscles following trigeminal stimulation. However, no evidence has so
      far been published of a crossed, short-latency, excitatory response resembling
      the early head extensor reflex seen in the cat. We seek its existence in humans.
      METHODS: The study was carried out in 14 voluntary healthy subjects. Percutaneous
      and surface electrical stimulation of the supraorbital and infraorbital nerves
      was performed with single, double and repetitive stimuli. Signals were recorded
      from the relaxed splenius and sternomastoid muscles bilaterally. RESULTS:
      Percutaneous stimulation of infraorbital nerve with single stimuli evoked an
      early response in the contralateral splenius muscle, with onset latency ranging
      from 11 to 14 ms (HR1). This response was greatly facilitated by double or
      repetitive stimuli. Single stimuli also gave rise to two larger responses in all
      4 muscles in the latency ranges 50-70 ms (HR2) and 100-160 ms (HR3). Surface
      stimulation of one nerve alone could not elicit any early activity. Single
      surface stimuli delivered simultaneously to the supraorbital and infraorbital
      nerves evoked HR1 in only 5 subjects. CONCLUSIONS: We detected a crossed early
      reflex of the head extensor muscles to trigeminal stimuli. Its timing is similar
      to the 8-ms response seen in cats. The evidence provided suggests that the reflex
      is mediated by an oligosynaptic circuit and that it needs a strong spatial
      summation at central synapses.

PMID- 11595142
TI  - A double-dissociation of English past-tense production revealed by event-related
      potentials and low-resolution electromagnetic tomography (LORETA).
AB  - OBJECTIVES: Evidence of systematic double-dissociations of neural activity
      associated with the generation of regular and irregular past tense in healthy
      individuals may prove decisive in distinguishing between single- and dual-route
      models of morphological processing, because the former (connectionist models of
      morphological processing) have only been able to simulate double-dissociations of
      past-tense morphology as low-probability phenomena. METHODS: Twenty-eight channel
      event-related potentials (ERPs) were recorded in response to past-tense
      production and subsequently analyzed using a 3-stage strategy. RESULTS: A data
      driven algorithm temporally segmented the ERPs into 16 distinct epochs of stable
      field configuration (microstates). A space-oriented brain electric field analysis
      determined that one of those epochs, 288-321 ms after the verb stem presentation,
      showed significant differences between the regular and irregular verb conditions.
      As a further test of these results, a novel source localization technique that
      computes 3-dimensional distribution of cortical current density in the Talairach
      brain atlas--low-resolution electromagnetic tomography--found in the above
      microstate more activity for regulars in the right prefrontal and right temporal
      areas and for irregulars in the left temporal areas and the anterior cingulate
      cortex, which can be taken as evidence of systematic double-dissociation.
      CONCLUSIONS: The present results achieved with a source localization technique
      provide evidence of a two-way compartmentalization of neural activity
      corresponding to regular and irregular past tense, thus corroborating the dual
      mechanism character of verb morphology.

PMID- 11595143
TI  - Neuromagnetic source localization of auditory evoked fields and intracerebral
      evoked potentials: a comparison of data in the same patients.
AB  - OBJECTIVE: To compare the localizations of different neural sources (a) obtained
      from intracerebral evoked responses and (b) calculated from surface auditory
      evoked field responses recorded in the same subjects. Our aim was to evaluate the
      resolving power of a source localization method currently used in our laboratory,
      which is based on a recent spatio-temporal algorithm used in magneto
      encephalography (MEG). METHODS: Auditory evoked responses were studied in 4
      patients with medically intractable epilepsy. These responses were recorded from
      depth electrodes implanted in the auditory cortex for pre-surgical evaluation
      (stereo-electro-encephalography (SEEG)), as well as from surface captors (for
      MEG) placed on the scalp after removal of the depth electrodes. Auditory stimuli
      were clicks and short tone bursts with different frequencies. RESULTS: All middle
      latency components (from 13 to 70 ms post-stimulus onset) were recorded and
      localized (via SEEG) along Heschl's gyrus (HG). MEG reliably localized Pam and
      P1m in the same area of HG that intracerebral recordings localized them in. No
      significant delay between SEEG and MEG latencies was observed. Both methods
      suggest that N1 is generated from different sources in the intermediate and
      lateral parts of the HG and in the planum temporale (PT). The source of P2 (PT
      and/or Area 22) remains unclear and was in one case, localized in different
      regions according to the method used. This latter component may therefore also be
      generated by different sources. CONCLUSIONS: The results suggest that both
      techniques are useful and may be used together in a complementary fashion.
      Intracerebral recordings allow the researcher to validate and interpret surface
      recordings.

PMID- 11595144
TI  - Morphological and functional retinal impairment in Alzheimer's disease patients.
AB  - OBJECTIVE: Our study aims to assess the optic nerve fiber layer thickness in
      vivo, the function of the innermost retinal layer and whether a correlation
      exists between morphological and functional parameters in patients affected by
      Alzheimer's Disease (AD). METHODS: Seventeen AD patients (mean age 70.37+/-6.1
      years, best corrected visual acuity >8/10 with refractive error between +/-3 sf,
      intra-ocular pressure (IOP)<18 mmHg) were enrolled. They were compared to 14 age
      matched controls. Nerve fiber layer (NFL) thickness was measured by optical
      coherence tomography (OCT). Three different measurements in each quadrant
      (superior, inferior, nasal, and temporal) were taken and averaged. The data in
      all quadrants (12 values averaged) were identified as NFL Overall. Retinal
      function was assessed by pattern electroretinogram (PERG) recordings using high
      contrast (80%) checkerboard stimuli subtending 15 min of the visual arc and
      reversed at the rate of two reversals/s. RESULTS: In AD eyes, there was a
      significant (P<0.01) reduction in NFL thickness in each quadrant and in the NFL
      Overall evaluation compared with the values observed in control eyes. PERGs
      showed a significant (P<0.01) delay in N35, P50 and N95 implicit times, and
      reduction in N35-P50 and P50-N95 amplitudes. NFL Overall values were
      significantly correlated (P<0.01) to the PERG P50 and N95 implicit times and P50
      N95 amplitude. No correlations (P>0.01) between NFL values and other PERG
      parameters (N35 implicit time, N35-P50 amplitude) were found. CONCLUSIONS: Our
      results suggest that in AD patients, there is a reduction of NFL thickness
      evaluated in vivo by OCT and this morphological abnormality is related to a
      retinal dysfunction as revealed by abnormal PERG responses.

PMID- 11595145
TI  - Scalp topography of ultralate (C-fibres) evoked potentials following thulium YAG
      laser stimuli to tiny skin surface areas in humans.
AB  - AIM: To investigate (1) the scalp topography of ultralate laser evoked potentials
      (LEPs) related to C-fibre activation, which can directly be obtained by thulium
      YAG (Tm YAG) laser stimulation of tiny skin surface areas (about 0.23 mm(2)) and
      (2) the influence of the performance of a motor task on ultralate LEPs. METHODS:
      Laser stimuli were applied to the dorsum of the left hand. LEPs were recorded
      with 58 scalp electrodes from 9 healthy subjects in two different conditions,
      with and without a reaction time (RT) task (press a button upon detection).
      RESULTS: On high resolution electroenchephalogram recordings, ultralate LEPs were
      characterized by a broad positive component (peak latency: 1133+/-91 ms) with
      maximum amplitude about the vertex. Moreover, the performance of a RT task had no
      influence on latency, amplitude and topographical patterns of two maps chosen at
      the positive peak latency in ultralate LEPs. Nevertheless, a negative inflexion
      (latency 1300 ms) appeared after the positive component in the task condition
      possibly reflecting movement-related potentials. CONCLUSION: Tm YAG laser
      stimulation of tiny skin surface areas allows recording the dynamic scalp
      topography of ultralate (C-fibres) LEPs, with or without the performance of a RT
      task.

PMID- 11595146
TI  - Characteristics of habituation of the sympathetic skin response to repeated
      electrical stimuli in man.
AB  - OBJECTIVES: To study the effect of repeating electrical peripheral nerve
      stimulation on latency, duration and amplitude of the sympathetic skin response
      (SSR). METHODS: SSRs were elicited in all limbs by median and peroneal nerves
      stimuli. In 10 subjects, 20 stimuli were applied at random time intervals (15-20
      s). Another test was performed in 7 subjects using the same protocol, but
      switching the stimulation site every 5 or 10 stimuli without warning. RESULTS:
      The mean amplitude of right palmar response to right peroneal nerve stimulation
      decreased from 5.05+/-0.76 (SEM) mV at the first stimulus to 1.23+/-0.42 mV at
      the 20th stimulus (P<0.001). The latency did not change significantly (1473+/-82
      to 1550+/-90 ms, P>0.1), while the duration increased (1872+/-356 to 3170+/-681
      ms, P<0.001). Stimulation and recording at other sites showed similar trends.
      Changing the stimulation site failed to alter the adaptation process in terms of
      amplitude, latency or duration. CONCLUSIONS: Changes in amplitude and duration of
      the SSRs to repeated electrical stimuli can occur in presence of constant latency
      and appear to be independent of the source of sensory input. Peripheral sweat
      gland mechanisms may be involved in the loss of amplitude and increase in
      duration of the SSR during habituation.

PMID- 11595147
TI  - Simultaneous recording of late and ultra-late pain evoked potentials in
      fibromyalgia.
AB  - OBJECTIVE: To characterize laser evoked potentials (LEP), pain psychophysics and
      local tissue response in fibromyalgia patients. METHODS: LEP were recorded in 14
      women with fibromyalgia in response to bilateral stimulation of tender and
      control points in upper limbs by 4 blocks of 20 stimuli at each point.
      Subsequently, heat pain thresholds were measured and supra-threshold magnitude
      estimations of heat pain stimuli were obtained on a visual analogue scale.
      Finally, the extent of the local tissue response induced by the previous stimuli
      was evaluated. RESULTS: Laser stimuli elicited two long latency waves: A late
      wave (mean latency 368.9+/-66.9 ms) in most patients (13/14) from stimuli at all
      points, and an ultra-late wave (mean latency 917.3+/-91.8 ms) in 78.5% of the
      patients at the control points and in 71.4% at the tender points. Amplitude of
      ultra-late waves was higher at the tender points (20.67+/-11.1 microV) than at
      the control points (10.47+/-4.1 microV) (P=0.016). Pain thresholds were lower in
      the tender (41.2+/-2.7 degrees C) than the control points (43.9+/-3.2 degrees C)
      (P=0.008). Local tissue response was significantly more intense at tender than
      control points (P=0.004). CONCLUSIONS: Ultra-late laser evoked potentials can be
      recorded simultaneously with late potentials. Our findings are compatible with
      presence of peripheral C-fiber sensitization, mostly at tender points, probably
      combined with generalized central sensitization of pain pathways in fibromyalgia.

PMID- 11595148
TI  - Absence of sleep EEG markers in fatal familial insomnia healthy carriers: a
      spectral analysis study.
AB  - OBJECTIVES: Fatal familial insomnia (FFI) is linked to a mutation at codon 178
      (C178) of the prion protein gene (PRNP). FFI is pathologically characterized by
      selective atrophy of the anteroventral and mediodorsal thalamic nuclei and
      clinically by loss of sleep, dysautonomia and motor signs. A key early
      polysomnographic sign of the disease onset is the loss of sleep spindling (sigma
      activity, SA). In FFI the loss of SA leads to the spectral representation of a
      sudden slow wave activity (SWA) increase from an awake state, the reaching of a
      stable plateau without oscillations, followed by abrupt fall down to REM sleep.
      We evaluated the presence of differences in the spectral sleep EEG pattern in FFI
      relatives carriers (C178(pos)) or non-carriers (C178(neg)) of the C178 mutation.
      METHODS: Seventeen healthy relatives of FFI patients, 8 carriers of the C178 FFI
      mutation in a preclinical condition and 9 non carriers, underwent two-night
      polysomnography. The absolute and relative EEG power of the 4 main bands (delta:
      SWA, 0.5-4.0 Hz; theta: TB, 4.5-8 Hz; alpha: AB, 8.5-12 Hz; sigma: SA, 12.5-16
      Hz) has been studied for the total sleep time, the period of delta increase after
      sleep onset, and the period of delta plateau. Multiple regression has been
      applied to investigate relations between the power of the bands studied and 3
      parameters: age, the gender of the subjects and the C178 genotype. RESULTS: Our
      study could not show evidence of differences in the sleep EEG composition between
      carriers and non-carriers of the C178 FFI mutation. CONCLUSIONS: The spectral
      analysis techniques we used were not able to disclose sleep EEG markers linked to
      the FFI C178(pos) in the preclinical condition. Key sleep EEG alteration become
      evident only at the clinical onset of the disease.

PMID- 11595149
TI  - Automated detection of trace alternant during sleep in healthy full-term neonates
      using discrete wavelet transform.
AB  - OBJECTIVE: To develop an automated procedure for scoring neonatal sleep states
      using signal processing which are based on visual pattern recognition techniques.
      METHODS: We are developing an automated computer system to study relationships
      among multiple non-cerebral physiologic measures and brain activity in newborn
      infants, and are evaluating the usefulness of a number of different time
      frequency domain transforms as potential diagnostic tools. RESULTS: Wavelet
      transforms yield excellent results in the detection of all twenty trace alternant
      quiet sleep segments for 6 full-term healthy infants. CONCLUSIONS: We suggest
      that this method will be useful for the automated detection of neonatal sleep
      states, and may help delineate when sleep cycle disturbances occur on either an
      environmental or disease basis. More accurate physiologic descriptions of
      neonatal state may improve the clinician's ability to assess functional brain
      organization for a given post-conceptional age as well as document functional
      brain maturation at progressively older corrected ages.

PMID- 11595150
TI  - Antero-posterior EEG changes during the wakefulness-sleep transition.
AB  - OBJECTIVES: To investigate the brain topography of the human sleep EEG along the
      antero-posterior axis during the wakefulness-sleep transition, by means of both a
      single Hz analysis and a grouped-frequency analysis of EEG changes. METHODS: EEG
      power values were calculated across a 1-28 Hz frequency range in a 1 Hz
      resolution during the wakefulness-sleep transition of 7 normal subjects.
      Topographical changes were assessed from C3-A2, C4-A1, Fpz-A1, Fz-A1, Cz-A1, Pz
      A1, Oz-A1 recordings, after averaging individual time series, aligned with
      respect to the onset of stage 2. RESULTS: The single Hz analysis showed that
      before sleep onset (SO), the <7 Hz slow frequencies were more prominent at the
      more anterior scalp locations; this anterior prominence was counterbalanced by a
      reciprocal prevalence across the >8 Hz frequencies of EEG activity from the
      occipital areas; while the >13 Hz fast frequencies were not characterized by
      significant antero-posterior differences. After SO, more EEG power was found in
      the range of slow frequencies at the centro-frontal scalp locations and a second
      peak of EEG activity was also revealed within the range of the sigma frequency,
      higher at the centro-parietal scalp locations. No consistent topographical
      changes were observed within the range of faster EEG frequencies. Grouped
      frequency analysis confirmed these results, also pointing to different changes in
      the alpha frequency as a function of the SO point. CONCLUSIONS: The results
      suggest that: (a) the alpha rhythm spreads anteriorly as the transition
      progresses; (b) several anterior areas first synchronize EEG activity; (c) the
      functional meaning of the EEG bands during the SO period should be partially
      revised with regard at least to alpha rhythm; (d) SO coincides with the start of
      stage 2.

PMID- 11595151
TI  - Temporal relationship of generalized epileptiform discharges to spindle frequency
      activity in childhood absence epilepsy.
AB  - OBJECTIVE: The hypothesis that the two main synchronizing mechanisms (spindle and
      delta oscillations) acting during non-rapid eye movement sleep show opposite
      relationship with the distribution of generalized epileptiform discharges (GEDs)
      during sleep was evaluated. METHODS: We studied the temporal relationship between
      the distribution of sleep GEDs and the dynamics of Sigma Activity (SA, 12-16 Hz)
      and Delta Activity (DA, 0.5-4.5 Hz) in 5 children affected by childhood absence
      epilepsy. RESULTS: Using correlation techniques, we found a high and positive
      correlation between GEDs and SA, while DA resulted negatively correlated with
      GEDs. CONCLUSION: Sleep generalized spike-and-slow-waves seems to be produced
      when spindle synchronizing mechanisms are active while DA production seem to
      exert an inhibiting role. Such a feature seems to be common to other childhood
      partial and undetermined epileptic syndromes.

PMID- 11595152
TI  - Warp-averaging event-related potentials.
AB  - OBJECTIVE: To align the repeated single trials of the event-related potential
      (ERP) in order to get an improved estimate of the ERP. METHODS: A new
      implementation of the dynamic time warping is applied to compute a warp-average
      of the single trials. The trilinear modeling method is applied to filter the
      single trials prior to alignment. Alignment is based on normalized signals and
      their estimated derivatives. These features reduce the misalignment due to
      aligning the random alpha waves, explaining amplitude differences in latency
      differences, or the seemingly small amplitudes of some components. RESULTS:
      Simulations and applications to visually evoked potentials show significant
      improvement over some commonly used methods. CONCLUSIONS: The new implementation
      of the dynamic time warping can be used to align the major components (P1, N1,
      P2, N2, P3) of the repeated single trials. The average of the aligned single
      trials is an improved estimate of the ERP. This could lead to more accurate
      results in subsequent analysis.

PMID- 11595153
TI  - A surface EMG analysis of sarcolemma excitability alteration and myofibre
      degeneration in Steinert disease.
AB  - OBJECTIVES: To apply surface electromyography (EMG) using low and high
      stimulation frequencies, to establish the contribution of myotonia and/or
      dystrophy to muscle impairment in subjects affected by myotonic dystrophy (MyD).
      METHODS: A motor point stimulation protocol, at 15 and 35 Hz, was carried out on
      the tibialis anterior (TA) of 25 MyD patients. These were subdivided into 3
      subgroups, MyD3 (9), MyD4 (10) and MyD5 (6), on the basis of their TA MRC score.
      The surface myoelectric signal was recorded and the average rectified value of
      amplitude (ARV) was evaluated. In 4 MyD5 patients we simultaneously recorded EMG
      and force. RESULTS: Each subgroup presented a characteristic ARV trend both at 15
      and 35 Hz - increasing in MyD3 (like the controls), slightly decreasing in MyD4
      and clearly decreasing in MyD5. The low frequency permitted a greater resolution
      of the statistical analysis. Two out of 4 patients showed an opposite trend of
      ARV with respect to the force, whereas the others presented a parallel decreasing
      trend. CONCLUSIONS: The analysis of the ARV during a stimulated contraction
      permits the identification and quantification of the sarcolemma excitability
      alteration and/or the myofibre degeneration contributing to muscle impairment in
      MyD. The lower frequency is more sensitive and offers better inter-experiment
      repeatability.

PMID- 11595154
TI  - Decreased EMG inhibition following electrical stimulation over muscle tendons in
      myopathies.
AB  - OBJECTIVE: To assess the central EMG inhibitory action of tendon afferent input
      in muscle diseases. METHODS: The EMG inhibition elicited by electrical
      stimulation over muscle tendons was tested in 13 healthy voluntary subjects and 8
      patients who had a primary muscle disease with a mild force deficit. Electrical
      stimuli were delivered to the tendon of the extensor carpi radialis muscle at the
      wrist during tonic voluntary isometric contraction at 50% of the maximum EMG
      level. The EMG signal was recorded by surface electrodes over the extensor carpi
      radialis muscle. RESULTS: The prestimulus background EMG level was reduced in 7
      out 8 of the patients. Both groups had the same phases of EMG modulation
      following tendon stimulation (TE1, TI1, TE2) and their latency and amplitude did
      not differ significantly. Conversely, the area of TI1 was significantly larger
      (i.e. the inhibition decreased) in patients ([mean+/-SD] absolute area:
      controls=4.1+/-1.6 mVms, patients=6.9+/-2.9 mVms, P<0.05). CONCLUSIONS: In muscle
      dysfunction there are serial 'upstream' changes of central inhibitory systems,
      probably to maximize the residual muscle power of the affected muscle.

PMID- 11595155
TI  - Proximal motor conduction evaluated by transcranial magnetic stimulation in
      acquired inflammatory demyelinating neuropathies.
AB  - OBJECTIVES: To evaluate conduction abnormalities in the proximal motor nerve in
      patients with acquired inflammatory demyelinating neuropathies by transcranial
      magnetic stimulation (TMS). METHODS: TMS intensity and background voluntary
      contraction (BVC) to evoke maximal size of motor evoked potential (MEP) in hand
      muscle were investigated in 24 normal subjects. Effect of experimentally induced
      conduction block by injecting local anesthetics in the peripheral nerve on MEP
      size was also studied in two normal subjects. In 22 patients with inflammatory
      demyelinating neuropathies, maximal MEPs were recorded in the deteriorating and
      recovery stages of the illness. RESULTS: In normal subjects, the MEP became
      maximal with 30-50% of maximal BVC and at more than 80% the maximal stimulator
      output of the 2.0 T circular coil. The change in MEP size well reflected the
      degree of conduction block induced by local anesthetics. Findings for patients
      suggested conduction abnormalities proximal to axilla in 9 patients, and that the
      abnormal reduction of Erb CMAP was the result of submaximal stimulation, not true
      conduction block, in 3 patients. The increase in MEP/wrist CMAP ratio was better
      correlated with improvement in muscle strength than with change in the axilla or
      Erb CMAP/wrist CMAP ratio. CONCLUSIONS: Problems such as conduction abnormalities
      in the motor tract of the central nervous system could not fully be excluded, but
      we consider that maximal MEP size can be used to predict proximal motor nerve
      conduction abnormalities.

PMID- 11595156
TI  - Symptoms and neurophysiological picture of carpal tunnel syndrome in pregnancy.
AB  - OBJECTIVE: To evaluate the incidence of carpal tunnel syndrome (CTS) in pregnancy
      through a validated and multiperspective assessment of CTS. METHODS: During 2000,
      the Italian CTS study group focussed on the occurrence of CTS in women during the
      final stages of pregnancy, enrolled in 7 Italian centers. In addition to the
      physician-centered and neurophysiologic traditional evaluations, we used a
      validated patient-oriented measurement to obtain more comprehensive and
      consistent data for severity of symptoms and functional impairment. RESULTS: In
      our study, CTS was clinically diagnosed in more than half of women (62%).
      Neurophysiological evaluation provided diagnosis of CTS in around half of women
      (43% were positive in one hand at least). Our study provides evidence, reported
      here for the first time, of a correlation between edema and neurophysiological
      picture. Similarly, our study provides a correlation between validated patient
      oriented measurement and edema. Moreover, a significant correlation between a
      negative trend (subjectively assessed) and smoking and alcohol consumption was
      observed. CONCLUSIONS: Our observations confirm that the edema of the tissues in
      the carpal tunnel could induce a mechanical compression of the nerve. Moreover,
      our data suggest that smoking and alcohol consumption have a negative role in the
      evolution of the syndrome probably due to impairment of the microcirculation.

PMID- 11595161
TI  - WT1 proteins: functions in growth and differentiation.
AB  - The Wilms' tumor 1 gene (WT1) has been identified as a tumor suppressor gene
      involved in the etiology of Wilms' tumor. Approximately 10% of all Wilms' tumors
      carry mutations in the WT1 gene. Alterations in the WT1 gene have also been
      observed in other tumor types, such as leukemia, mesothelioma and desmoplastic
      small round cell tumor. Dependent on the tumor type, WT1 proteins might either
      function as tumor suppressor proteins or as survival factors. Mutations in the
      WT1 gene can also result in congenital abnormalities as observed in Denys-Drash
      and Frasier syndrome patients. Mouse models have proven the critical importance
      of WT1 expression for the development of several organs, including the kidneys,
      the gonads and the spleen. The WT1 proteins seem to perform two main functions.
      They regulate the transcription of a variety of target genes and may be involved
      in post-transcriptional processing of RNA. The WT1 gene encodes at least 24
      protein forms. These isoforms have partially distinct biological functions and
      effects, which in many cases are also specific for the model system in which WT1
      is studied. This review discusses the molecular mechanisms by which the various
      WT1 isoforms exert their functions in normal development and how alterations in
      WT1 may lead to developmental abnormalities and tumor growth.

PMID- 11595162
TI  - Genomic structure of human GM3 synthase gene (hST3Gal V) and identification of
      mRNA isoforms in the 5'-untranslated region.
AB  - GM3 synthase, which transfers CMP-NeuAc with an alpha2,3-linkage to a galactose
      residue of lactosylceramide, plays a key role in the biosynthesis of all complex
      gangliosides. In this study, cDNA and genomic clones encoding human GM3 synthase
      (hST3Gal V) were isolated, and the structural organization of the gene was
      determined. The hST3Gal V cDNA was identical in the coding region with cDNA that
      has been cloned previously from the HL-60 cells but different in the 5'
      untranslated region (UTR). The hST3Gal V gene consisted of nine exons, which span
      approximately 44 kb, with exons ranging in size from 112 to 1242 bp. The coding
      region was located in exons 4-9, and all exon-intron boundaries except the
      acceptor site of intron 1 followed the GT-AG rule. The expression of this gene
      was highly restricted in both human fetal and adult tissues. By comparison of the
      nucleotide sequences of the genomic DNA with cDNA sequences including 5'-RACE
      products, we identified four isoforms (types 1-4) of the hST3Gal V mRNA that
      differ only in the 5'-UTR. Structural analysis of these isoforms suggests that
      mRNA isoforms of hST3Gal V are produced by a combination of alternative splicing
      and alternative promoter utilization.

PMID- 11595163
TI  - Expression of P21(WAF1/CIP1/SID1) cyclin-dependent kinase inhibitor in
      hematopoietic progenitor cells.
AB  - P21(Waf1/Cip1/Sid1) is a critical component of biomolecular pathways leading to
      the G(1) arrest evoked in response to DNA damage, growth arrest signals and
      differentiation commitment. It belongs to the Cip/Kip class of cyclin-dependent
      kinase inhibitors and is at least partly regulated by p53. P21(Waf1/Cip1/Sid1)
      functional inactivation possibly resulting from mutations of the gene itself or,
      more likely, from p53 mutations may be critical for either the cell fate
      following DNA-damaging insults or clonal evolution toward malignancy. In the
      study presented here we describe a competitive polymerase chain reaction (PCR)
      strategy whose sensitivity and reproducibility enable us to attain a precise
      quantitation of p21(Waf1/Cip1/Sid1) expression levels in hematopoietic
      progenitors, the cell compartment which mostly suffers from the side effects of
      genotoxic drugs in use for cancer cure. The strategy was set in the M07 factor
      dependent hematopoietic progenitor cell line. We confirmed that its
      p21(waf1/cip1/sid1) constitutive expression level is very low and up-modulated by
      DNA-damaging agents: ionizing radiations and ultraviolet light. Gene up
      modulation resulted in checkpoint activation and, in particular, in a significant
      G(1) arrest, required for either the repair of damaged DNA sequences or apoptotic
      cell death. Our competitive PCR strategy was further validated in CD34(+)
      purified hematopoietic progenitors from healthy donors mobilized into the
      peripheral blood by granulocyte colony-stimulating factor and intended for
      allogeneic bone marrow transplantation. The constitutive p21(WAF1/CIP1/SID1)
      expression levels, measured in three separate harvests, were very low and no
      significant differences were apparent. Our results support the use of a
      competitive PCR strategy as a useful tool for clinical purposes, to assess the
      individual biomolecular response of early hematopoietic progenitors to
      antiblastic drugs.

PMID- 11595164
TI  - Identification of tumor suppressor candidate genes by physical and sequence
      mapping of the TSLC1 region of human chromosome 11q23.
AB  - Loss of heterozygosity for a locus on human chromosome 11q22-23 is observed at
      high frequency in non-small cell lung carcinoma (NSCLC). Introduction of a 1.1 Mb
      fragmented yeast artificial chromosome (YAC) mapping to this region completely
      suppresses the tumorigenic properties of a human NSCLC cell line, A549. Smaller
      fragmented YACs give partial but not complete suppression. To further localize
      the gene(s) responsible for this partial suppression, a bacterial artificial
      chromosome (BAC) and P1-based artificial chromosome (PAC) contig was constructed,
      completely spanning the candidate region. End sequence generated in the
      construction of the BAC/PAC contig identified a previously unmapped EST and
      served to order genomic sequence contigs from the publicly available Celera
      Genomics (CG) and Human Genome Project (HGP) efforts. Comparison showed that CG
      provided larger contigs, while HGP provided more coverage. Neither CG nor HGP
      provided complete sequence coverage, alone or in combination. The sequence was
      used to map 110 ESTs and to predict new genes, including two GenScan gene
      predictions that overlapped ESTs and were shown to be differentially expressed in
      tumorigenic and suppressed A549 cell lines.

PMID- 11595165
TI  - A novel copper-regulated promoter system for expression of heterologous proteins
      in Schizosaccharomyces pombe.
AB  - The increasing use of the fission yeast Schizosaccharomyces pombe as a model
      organism for elucidating the mechanisms of critical biological processes such as
      cell-cycle control, DNA replication, and stress-mediated signal transduction has
      fostered the development and utilization of expression systems for gene function
      analysis. Using the promoter of the ctr4(+) copper transporter gene from S.
      pombe, we created a series of vectors, named pctr4(+)-X, which regulate the
      expression of heterologous genes as a function of copper availability. In this
      system, the addition of copper ions at levels that are non-toxic to yeast cells
      represses gene expression, while copper deprivation strongly induces gene
      expression. Conveniently, changes of growth medium or carbon sources are not
      required to shut down or induce gene expression. The Cu-starvation-mediated
      inducible expression system is rapid, producing heterologous proteins within 3 h,
      with sustained expression of proteins that persists for several hours. The
      pctr4(+)-X expression vectors harbor unique restriction sites constructed in
      frame to DNA sequences encoding for epitope tags, which facilitate the detection
      or purification of the heterologous proteins using commercially available
      antibodies and affinity columns. Furthermore, the pctr4(+)-X copper-regulatable
      protein expression vectors have been constructed with three different selectable
      markers, offering more versatility for studying gene function in fission yeast.

PMID- 11595166
TI  - The murine genome contains one functional gene and two pseudogenes coding for the
      16 kDa proteolipid subunit of vacuolar H(+)-ATPase.
AB  - We cloned the genomic genes encoding the murine 16 kDa subunit (proteolipid,
      PL16) of vacuolar H(+)-ATPase (V-ATPase) and determined their nucleotide
      sequences. At least three independent genes were found in the murine genome. One
      gene consisted of three exons and was largely identical in sequence to that of
      PL16 cDNA reported previously (Hanada et al., Biochem. Biophys. Res. Commun. 176
      (1991) 1062). In the 5'-flanking region of this gene, several possible
      transcriptional cis-elements were found. TATA and CAAT sequences were not found,
      which is characteristic for promoters of house-keeping genes. The other two genes
      identified did not contain introns. One of these genes had an open reading frame
      that potentially encoded PL16 but contained six amino acid substitutions and a
      frame-shift mutation that would result in a truncated protein unable to
      participate in V-ATPase activity. The other gene had the same sequence in the
      reading frame as that in the cDNA. However, this gene contained a polyA sequence
      at the same position where polyA is normally added to mRNA. The gene also had 15
      bp repetitive sequences near the transcription initiation site and next to the
      polyA sequence. These observations suggest that this gene may have been generated
      by the insertion of reverse-transcribed double-stranded cDNA, as is usually
      observed for pseudogenes. In conclusion, there is a single functional PL16 gene
      and two pseudogenes in the murine genome. It is unlikely that PL16 isoforms
      contribute to variation in V-ATPase function.

PMID- 11595167
TI  - Molecular cloning and characterization of a steroid receptor-binding regulator of
      G-protein signaling protein cDNA.
AB  - Steroid hormone receptors are composed of six major functional domains, i.e. the
      A/B domains as the activation function 1 domain (AF-1), domain C as the DNA
      binding domain, domain D as a hinge domain and domain E/F as the ligand-dependent
      transcriptional domain (AF-2). They regulate gene transcription through
      interactions with various nuclear factors of their domains, such as AF-1 and AF
      2. We have insufficient knowledge of the function of the DNA-binding domain
      (domain C) except for its DNA-binding function or the hinge domain (domain D).
      Therefore, we attempted to identify factors interacting with the domains by using
      a yeast two-hybrid system. Domains C and D of estrogen receptor alpha were used
      as a bait to isolate cDNA clones from a rat ovary cDNA library. We isolated the
      cDNA clone of a novel steroid receptor-binding protein bearing the regulator of G
      protein signaling (RGS) designated as SRB-RGS. The protein repressed the
      transcriptional activity of estrogen receptor alpha, suggesting cross-talk of
      steroid hormones and peptide hormones (or growth factors) for signal
      transductions mediated by SRB-RGS.

PMID- 11595168
TI  - Organizations and promoter analyses of the human and the mouse genes for PACT,
      the protein-activator of the interferon-induced protein kinase, PKR.
AB  - PACT is an activator of the protein kinase, PKR. Here we report the isolation and
      the characterization of the mouse Pact gene. It contains eight exons ranging in
      size from 79 to 630 bp spanning a region of 18 kb with the largest and smallest
      introns being 3700 and 500, respectively. The human PACT gene, as analyzed from
      sequence available in the GenBank database, has a very similar organization. The
      5' flanking regions of both mouse and human PACT genes are devoid of TATA boxes
      but are rich in GC boxes. Although there are putative binding sites of numerous
      transcription factors on both promoters, their organizations and identities are
      different. For examining promoter activities, about 2 kb of DNA 5' to the
      transcription start sites of both genes was cloned upstream of a reporter
      luciferase gene. Transient transfection assays demonstrated that both promoters
      are strong. Deletion analyses revealed that most of the positive cis-elements lie
      within 400 bp upstream of the transcription start sites of both mouse and human
      PACT genes.

PMID- 11595169
TI  - The iodocyanopindolol and SM-11044 binding protein belongs to the TM9SF
      multispanning membrane protein superfamily.
AB  - SM-11044 is the only beta-adrenergic agonist that inhibits guinea pig eosinophil
      chemotaxis and induces relaxation of depolarized rat colon tonus. We have
      previously reported the purification of a 34 kDa photoaffinity-labeled SM-11044
      binding protein (SMBP) from rat colon that may mediate the biological effects of
      the ligand and that differs from all known monoamine receptors (Sugasawa et al.,
      J. Biol. Chem. 272 (1997) 21244). The present report describes partial amino acid
      sequence of rat SMBP and molecular cloning of corresponding human SMBP (hSMBP)
      cDNA. This cDNA encodes a 588 amino acid residue polypeptide comprising a signal
      peptide, a long hydrophilic amino-terminal region, and a highly hydrophobic C
      terminal portion organized into nine putative transmembrane domains. The sequence
      and structure of hSMBP shows homology to members of a new transmembrane protein 9
      superfamily (TM9SF). Comparison of hSMBP with related protein sequences from
      yeast, plant and human revealed two subgroups within TM9SF. The members of these
      groups differ in length and have characteristic amino acid sequence motifs in
      their amino-terminal portion. Northern blot analysis revealed two major SMBP
      mRNAs, at 3.4 and 3.8 kb, that were present in all the human tissues examined.
      Western blot experiments detected SMBP as a 70 kDa protein that may be further
      cleaved into an active 34 kDa N-terminal polypeptide. Stable Chinese Hamster
      Ovary cell transfectants expressing hSMBP cDNA displayed specific binding of
      [(125)I]iodocyanopindolol that was displaced by SM-11044 in a dose-dependent
      manner. Thus, SMBP is the first member of TM9SF with functional ligand binding
      properties, suggesting that some of these integral membrane proteins may function
      as channels, small molecule transporters or receptors.

PMID- 11595170
TI  - Characterization of the genomic structure and tissue-specific promoter of the
      human nuclear receptor NR5A2 (hB1F) gene.
AB  - The human homologue of the Drosophila melanogaster orphan nuclear receptor fushi
      tarazu factor 1 (Ftz-F1), NR5A2 (hB1F), was initially identified as a regulatory
      factor that binds and activates enhancer II of hepatitis B virus. NR5A2 (hB1F) is
      expressed specifically in pancreas and liver, playing important roles in the
      regulation of several liver-specific genes. A detailed analysis on the genomic
      structure and promoter activity will greatly promote future studies on the
      function of the NR5A2 (hB1F) gene. In this report, a bacterial artificial
      chromosome clone and several phage clones covering the NR5A2 (hB1F) gene were
      isolated and the complete genomic sequence was obtained. Alignment of different
      cDNAs of the NR5A2 (hB1F) gene with the genomic sequence facilitated the
      delineation of its structural organization, which spans over 150 kb and consists
      of eight exons interrupted by seven introns. RT-PCR and 3'-RACE revealed that
      utilization of two polyadenylation signals results in the 3.8 and 5.2 kb
      transcripts that were observed previously. The transcription start site of the
      NR5A2 (hB1F) gene was mapped downstream of a canonical TATA box. An upstream
      fragment containing binding sites for several liver-specific and ubiquitous
      transcription factors exhibits hepatocyte-specific promoter activity. Transient
      transfections indicated that hepatocyte nuclear factors HNF1 and HNF3beta could
      activate NR5A2 (hB1F) promoter.

PMID- 11595171
TI  - Molecular cloning of natriuretic peptide receptor A from bullfrog (Rana
      catesbeiana) brain and its functional expression.
AB  - A comparative study of natriuretic peptide receptor (NPR) was performed by
      cloning the NPR-A receptor subtype from the bullfrog (Rana catesbeiana) brain and
      analyzing its functional expression. Like other mammalian NPR-A receptors, the
      bullfrog NPR-A receptor consists of an extracellular ligand binding domain, a
      hydrophobic transmembrane domain, a kinase-like domain and a guanylate cyclase
      domain. Sequence comparison among the bullfrog and mammalian receptors revealed a
      relatively low ( approximately 45%) similarity in the extracellular domain
      compared to a very high similarity ( approximately 92%) in the cytoplasmic
      regulatory and catalytic domains. Expression of NPR-A mRNA was detected in
      various bullfrog tissues including the brain, heart, lung, kidney and liver;
      highest levels were observed in lung. Functional expression of the receptor in
      COS-7 cells revealed that frog atrial natriuretic peptide (ANP) and brain
      natriuretic peptide (BNP) elicited cyclic guanosine 3'5'-monophosphate production
      by stimulating the receptor in a dose-dependent manner from 10(-10) M
      concentrations. Rat ANP was also effective in stimulating the frog receptor
      whereas rat BNP and porcine BNP were less responsive to the receptor. On the
      other hand, frog C-type natriuretic peptide (CNP) as well as porcine CNP
      stimulated the receptor only at high concentrations (10(-7) M). This clearly
      indicates that the bullfrog receptor is a counterpart of mammalian NPR-A, and is
      specific for ANP or BNP but not for CNP.

PMID- 11595172
TI  - Cooperative effects by the initiation codon and its flanking regions on
      translation initiation.
AB  - The purine-rich Shine-Dalgarno (SD) sequence located a few bases upstream of the
      mRNA initiation codon supports translation initiation by complementary binding to
      the anti-SD in the 16S rRNA, close to its 3' end. AUG is the canonical initiation
      codon but the weaker UUG and GUG codons are also used for a minority of genes.
      The codon sequence of the downstream region (DR), including the +2 codon
      immediately following the initiation codon, is also important for initiation
      efficiency. We have studied the interplay between these three initiation
      determinants on gene expression in growing Escherichia coli. One optimal SD
      sequence (SD(+)) and one lacking any apparent complementarity to the anti-SD in
      16S rRNA (SD(-)) were analyzed. The SD(+) and DR sequences affected initiation in
      a synergistic manner and large differences in the effects were found. The gene
      expression level associated with the most efficient of these DRs together with
      SD(-) was comparable to that of other DRs together with SD(+). The otherwise weak
      initiation codon UUG, but not GUG, was comparable with AUG in strength, if placed
      in the context of two of the DRs. The +2 codon was one, but not the only,
      determinant for this unexpectedly high efficiency of UUG.

PMID- 11595173
TI  - Cloning and characterization of a new soluble murine J-domain protein that
      stimulates BiP, Hsc70 and DnaK ATPase activity with different efficiencies.
AB  - Hsp70s perform many functions in the cell through their ATPase activity that is
      stimulated by a genuine partner that contains a highly conserved so called J
      domain. Here we report the cloning and characterization of a new J-domain protein
      named MmDjC7. The complete cDNA encodes a putative soluble 22 kDa protein that
      contains a conserved J-domain, but lacks the G/F- and C-rich regions found in the
      bacterial Escherichia coli DnaJ. Northern analysis revealed that mmDjC7 mRNA (0.9
      kb) is most abundant in the heart and liver tissues. Recombinant hexahistidine
      tagged MmDjC7 (25 kDa) was efficiently expressed in E. coli and purified to
      homogeneity. MmDjC7 stimulates the ATPase activity of murine BiP, Hsc70 and E.
      coli DnaK, albeit with very different molar ratios that vary from 1:2 (for
      BiP/MmDjC7) to 1:10 (for DnaK/MmDjC7). MmDjC7 thus appears to be a new J-domain
      protein that can possibly interact with more than one Hsp70.

PMID- 11595174
TI  - Molecular cloning and characterization of the mouse and human TUSP gene, a novel
      member of the tubby superfamily.
AB  - We report here the cloning and characterization of a novel gene belonging to the
      tubby superfamily proteins (TUSP) in mouse and human. The mouse Tusp cDNA is 9120
      bp in length and encodes a deduced protein of 1547 amino acids, while the human
      TUSP gene is 11,127 bp and encodes a deduced protein of 1544 amino acids. The
      human and mouse genes are 87% identical for their nucleotide sequences and 85%
      identical for their amino acid sequences. The protein sequences of these genes
      are 40-48% identical to other tubby family proteins at the C-terminal conserved
      'tubby domain'. In addition, the TUSP proteins contain a tubby signature motif
      (FXGRVTQ), two bipartite nuclear localization signals (NLSs) at the C-terminal,
      two proline-rich regions, one WD40 repeat region and one suppressor of cytokines
      signaling domain. Transfection assay with green fluorescent protein-tagged TUSP
      expression constructs showed that the complete TUSP protein and the N-terminal
      portion of TUSP are localized in the cytoplasm but the C-terminal portion with
      the two NLSs produced distinct dots or spots localized in the cytoplasm. Northern
      blotting analysis showed that the major transcript with the complete coding
      sequence is expressed mainly in the brain, skeletal muscle, testis and kidney.
      Radiation hybrid mapping localized the mouse gene to chromosome 17q13 and the
      human TUSP gene to chromosome 6q25-q26 near the type 1 diabetes gene IDDM5.
      However, association analysis in diabetic families with a polymorphic
      microsatellite marker did not show any evidence for association between TUSP and
      type 1 diabetes. The precise biological function of the tubby superfamily genes
      is still unknown; the highly conserved tubby domain in different species,
      however, suggests that these proteins must have fundamental biological functions
      in a wide range of multi-cellular organisms.

PMID- 11595175
TI  - The sedlin gene for spondyloepiphyseal dysplasia tarda escapes X-inactivation and
      contains a non-canonical splice site.
AB  - Mutations in the sedlin gene cause spondyloepiphyseal dysplasia tarda (SEDT), a
      rare X-linked chondrodysplasia. Affected males suffer short stature, deformation
      of the spine and hips, and deterioration of intervertebral discs with
      characteristic radiographic changes in the vertebrae. We have sequenced two full
      length cDNA clones corresponding to the human sedlin gene. The longest cDNA is
      2836 bp, containing a 218 bp 5' untranslated region, a 423 bp coding region, and
      a 2195 bp 3' untranslated region. The second cDNA does not contain exon 2,
      suggesting alternative splicing. Sedlin was finely mapped in Xp22.2 by Southern
      blot analysis on a yeast artificial chromosome/bacterial artificial chromosome
      map. Comparison of the cDNA sequence and genomic sequence identified six sedlin
      exons of 67, 142, 112, 147, 84, and 2259 bp. The corresponding introns vary in
      size from 339 to 14,061 bp. Splice site sequences for four of the five introns
      conform to the GT/AG consensus sequences, however, the splice site between exons
      4 and 5 displays a rare non-canonical splice site sequence, AT/AC. Northern blot
      analysis showed expression of the sedlin gene in all human adult and fetal
      tissues tested, with the highest levels in kidney, heart, skeletal muscle, liver,
      and placenta. Four mRNA sizes were detected with the major band being 3 kb and
      minor bands of 5, 1.6, and 0.9 kb (the smallest product may reflect a sedlin
      pseudogene). Sedlin is expressed from both the active and the inactive human X
      chromosomes helping to explain the recessive nature and consistent presentation
      of the disease. Human sedlin shows homology to a yeast gene, which conditions
      endoplasmic reticulum/golgi transport. Characterization of the human sedlin cDNA
      and determination of the sedlin gene structure enable functional studies of
      sedlin and elucidation of the pathogenesis of SEDT.

PMID- 11595176
TI  - The genomic structure of the human SPEC1 gene reveals complex splicing and close
      promoter proximity to the AF1q translocation gene.
AB  - SPECs are small Cdc42 signaling molecules. In mammals, two genes, SPEC1 and
      SPEC2, encode proteins of 79 and 84 amino acid residues, respectively. Here we
      report the expression and genomic organization of the human SPEC1 gene. Using
      Northern blot analysis, three major SPEC1 mRNA transcripts of 1.6, 3.3, and 6.3
      kb were detected. Identification and sequencing of different sized SPEC1 cDNA
      clones revealed that the transcript size heterogeneity was due to alternative
      splicing in the 3'-untranslated region. In addition, a distinct SPEC1 splice
      variant from within the coding sequence, SPEC1-beta, was identified and detected
      in a variety of human tissues. Analysis of the genomic organization of SPEC1
      revealed that the coding sequence of the SPEC1 isoform was derived from exons 2,
      3 and 4, while the SPEC1-beta isoform was derived from exon 2 and a read-through
      event of intron 2. Examination of the 5'-end of the SPEC1 genomic sequence
      revealed that AF1q, a previously identified gene involved in translocations with
      the MLL (mixed-lineage leukemia) gene, was 631 bp away in a head-to-head
      orientation. This intergenic sequence containing the putative promoter region for
      both SPEC1 and AF1q genes did not contain a TATA box or CAAT box. Transfection
      experiments using an AF1q promoter luciferase reporter construct in a variety of
      cells including Cos1 cells, Jurkat T-cells, MCF-7 breast cancer cells, and NIH
      3T3 fibroblasts showed no promoter activity. In contrast, a SPEC1 promoter
      luciferase reporter construct showed high levels of reporter activity in Cos1 and
      MCF-7 cells, low activity in NIH-3T3 fibroblasts and no activity in Jurkat T
      cells. These promoter analyses suggest that although SPEC1 and AF1q genes share
      the same promoter region, they are not coordinately regulated.

PMID- 11595177
TI  - High-density sampling of a bacterial operon using mRNA differential display.
AB  - We have implemented a simplified high throughput approach to differential display
      in order to identify transcriptionally regulated genes in bacteria. In contrast
      with the few previous applications of differential display to prokaryotes, we use
      a large number of primers which allows for a high-density sampling of the mRNA
      population and the identification of many differentially amplified DNA fragments.
      From the overlap of these short sequences, long contiguous sequences that encode
      several genes can be assembled. The multiplicity of sampling provides a strong
      indication that the genes identified are indeed differentially regulated. As a
      test case, we looked for the genes involved in the degradation of 2,4
      dinitrophenol (2,4-DNP) in a Rhodococcus erythropolis strain, HL PM-1. In this
      experiment a long polycistronic mRNA was sampled repeatedly. The induction of
      these genes by 2,4-DNP was confirmed by dot blot analysis and two of them were
      confirmed to be involved in the degradation of 2,4-DNP. This work shows that mRNA
      differential display is an important tool for the identification of metabolic
      genes in prokaryotes.

PMID- 11595178
TI  - HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a global regulator of cellular and systemic
      O(2) homeostasis in animals. A molecular basis for O(2)-regulated expression of
      the HIF-1 alpha subunit has now been determined, providing a mechanism for
      changes in gene expression in response to changes in cellular oxygenation.

PMID- 11595179
TI  - SP-RING for SUMO: new functions bloom for a ubiquitin-like protein.
AB  - SUMO is covalently linked to a variety of cellular proteins. Three groups now
      describe related E3-like factors that enhance transfer of SUMO to specific
      proteins. This family of factors includes proteins important for chromosome
      condensation, signal transduction, and ion channel biogenesis.

PMID- 11595180
TI  - Error-prone DNA polymerases: novel structures and the benefits of infidelity.
AB  - Studies on several recently discovered error-prone DNA polymerases reveal novel
      structures that may explain the low fidelity of this general class of enzymes, a
      number of which are involved in the replicative bypass (translesion synthesis) of
      base damage in DNA.

PMID- 11595181
TI  - Of mice and genome sequence.
AB  - Availability of the mouse genome sequence will have a major impact on the study
      of vertebrate evolution, mammalian biology, and animal models of human disease.
      Resources to explore genome biology in mice will maximize the effect of this
      watershed event.

PMID- 11595182
TI  - Guidance of cell migration by the Drosophila PDGF/VEGF receptor.
AB  - Directed cell migrations are important for development, but the signaling
      pathways and mechanisms responsible for guiding cell migration in vivo are poorly
      understood. Migration of border cells during Drosophila oogenesis is a simple and
      attractive model system in which to address these questions. We demonstrate that
      PVR, a receptor tyrosine kinase related to mammalian PDGF and VEGF receptors,
      acts in border cells to guide them to the oocyte. The oocyte is the source of a
      ligand for PVR, PDGF/VEGF factor 1 (PVF1). Intriguingly, the guidance function of
      PVR is largely redundant with that of EGFR. We present evidence implicating Rac
      and the Rac activator Mbc/DOCK180/CED-5 as mediators of the guidance signal.

PMID- 11595183
TI  - CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for
      phagocytosis and cell migration.
AB  - The C. elegans genes ced-2, ced-5, and ced-10, and their mammalian homologs
      crkII, dock180, and rac1, mediate cytoskeletal rearrangements during phagocytosis
      of apoptotic cells and cell motility. Here, we describe an additional member of
      this signaling pathway, ced-12, and its mammalian homologs, elmo1 and elmo2. In
      C. elegans, CED-12 is required for engulfment of dying cells and for cell
      migrations. In mammalian cells, ELMO1 functionally cooperates with CrkII and
      Dock180 to promote phagocytosis and cell shape changes. CED-12/ELMO-1 binds
      directly to CED-5/Dock180; this evolutionarily conserved complex stimulates a Rac
      GEF, leading to Rac1 activation and cytoskeletal rearrangements. These studies
      identify CED-12/ELMO as an upstream regulator of Rac1 that affects engulfment and
      cell migration from C. elegans to mammals.

PMID- 11595184
TI  - C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that
      regulate HIF by prolyl hydroxylation.
AB  - HIF is a transcriptional complex that plays a central role in mammalian oxygen
      homeostasis. Recent studies have defined posttranslational modification by prolyl
      hydroxylation as a key regulatory event that targets HIF-alpha subunits for
      proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Here,
      we define a conserved HIF-VHL-prolyl hydroxylase pathway in C. elegans, and use a
      genetic approach to identify EGL-9 as a dioxygenase that regulates HIF by prolyl
      hydroxylation. In mammalian cells, we show that the HIF-prolyl hydroxylases are
      represented by a series of isoforms bearing a conserved 2-histidine-1-carboxylate
      iron coordination motif at the catalytic site. Direct modulation of recombinant
      enzyme activity by graded hypoxia, iron chelation, and cobaltous ions mirrors the
      characteristics of HIF induction in vivo, fulfilling requirements for these
      enzymes being oxygen sensors that regulate HIF.

PMID- 11595185
TI  - Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding.
AB  - Like other enveloped viruses, HIV-1 uses cellular machinery to bud from infected
      cells. We now show that Tsg101 protein, which functions in vacuolar protein
      sorting (Vps), is required for HIV-1 budding. The UEV domain of Tsg101 binds to
      an essential tetrapeptide (PTAP) motif within the p6 domain of the structural Gag
      protein and also to ubiquitin. Depletion of cellular Tsg101 by small interfering
      RNA arrests HIV-1 budding at a late stage, and budding is rescued by
      reintroduction of Tsg101. Dominant negative mutant Vps4 proteins that inhibit
      vacuolar protein sorting also arrest HIV-1 and MLV budding. These observations
      suggest that retroviruses bud by appropriating cellular machinery normally used
      in the Vps pathway to form multivesicular bodies.

PMID- 11595186
TI  - The shortest telomere, not average telomere length, is critical for cell
      viability and chromosome stability.
AB  - Loss of telomere function can induce cell cycle arrest and apoptosis. To
      investigate the processes that trigger cellular responses to telomere
      dysfunction, we crossed mTR-/- G6 mice that have short telomeres with mice
      heterozygous for telomerase (mTR+/-) that have long telomeres. The phenotype of
      the telomerase null offspring was similar to that of the late generation parent,
      although only half of the chromosomes were short. Strikingly, spectral
      karyotyping (SKY) analysis revealed that loss of telomere function occurred
      preferentially on chromosomes with critically short telomeres. Our data indicate
      that, while average telomere length is measured in most studies, it is not the
      average but rather the shortest telomeres that constitute telomere dysfunction
      and limit cellular survival in the absence of telomerase.

PMID- 11595187
TI  - Structural analysis of DNA replication fork reversal by RecG.
AB  - The stalling of DNA replication forks that occurs as a consequence of
      encountering DNA damage is a critical problem for cells. RecG protein is involved
      in the processing of stalled replication forks, and acts by reversing the fork
      past the damage to create a four-way junction that allows template switching and
      lesion bypass. We have determined the crystal structure of RecG bound to a DNA
      substrate that mimics a stalled replication fork. The structure not only reveals
      the elegant mechanism used by the protein to recognize junctions but has also
      trapped the protein in the initial stage of fork reversal. We propose a mechanism
      for how forks are processed by RecG to facilitate replication fork restart. In
      addition, this structure suggests that the mechanism and function of the two
      largest helicase superfamilies are distinct.

PMID- 11595188
TI  - Crystal structure of a Y-family DNA polymerase in action: a mechanism for error
      prone and lesion-bypass replication.
AB  - Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) is a DinB homolog that
      belongs to the recently described Y-family of DNA polymerases, which are best
      characterized by their low-fidelity synthesis on undamaged DNA templates and
      propensity to traverse normally replication-blocking lesions. Crystal structures
      of Dpo4 in ternary complexes with DNA and an incoming nucleotide, either correct
      or incorrect, have been solved at 1.7 A and 2.1 A resolution, respectively.
      Despite a conserved active site and a hand-like configuration similar to all
      known polymerases, Dpo4 makes limited and nonspecific contacts with the
      replicating base pair, thus relaxing base selection. Dpo4 is also captured in the
      crystal translocating two template bases to the active site at once, suggesting a
      possible mechanism for bypassing thymine dimers.

PMID- 11595189
TI  - Block of HAC1 mRNA translation by long-range base pairing is released by
      cytoplasmic splicing upon induction of the unfolded protein response.
AB  - Expression of the yeast transcription factor Hac1p, which controls the unfolded
      protein response, is regulated posttranscriptionally. Hac1p is only produced when
      an intron at the 3' end of its mRNA is removed by a nonconventional, regulated
      splicing reaction. We show that a previously unrecognized base-pairing
      interaction between the intron and the 5' untranslated region is required and
      sufficient to block mRNA translation. Unspliced HAC1 mRNA is stable, located in
      the cytosol, and is associated with polyribosomes, yet does not produce protein,
      indicating that the ribosomes engaged on the mRNA are stalled. We show that the
      polysomal, cytoplasmic pool of HAC1 mRNA is a substrate for splicing, suggesting
      that the stalled ribosomes may resume translation after the intron is removed.

PMID- 11595190
TI  - A posttermination ribosomal complex is the guanine nucleotide exchange factor for
      peptide release factor RF3.
AB  - The mechanism by which peptide release factor RF3 recycles RF1 and RF2 has been
      clarified and incorporated in a complete scheme for translation termination. Free
      RF3 is in vivo stably bound to GDP, and ribosomes in complex with RF1 or RF2 act
      as guanine nucleotide exchange factors (GEF). Hydrolysis of peptidyl-tRNA by RF1
      or RF2 allows GTP binding to RF3 on the ribosome. This induces an RF3
      conformation with high affinity for ribosomes and leads to rapid dissociation of
      RF1 or RF2. Dissociation of RF3 from the ribosome requires GTP hydrolysis. Our
      data suggest that RF3 and its eukaryotic counterpart, eRF3, have mechanistic
      principles in common.

PMID- 11595192
TI  - What have we learned about the biology of atherosclerosis? The role of
      inflammation.
AB  - In the past, we believed that atherosclerosis gradually and progressively led to
      the complete occlusion of an artery, thereby causing acute coronary events.
      However, we now understand that rupture of a nonstenotic, yet vulnerable
      atherosclerotic plaque frequently leads to an acute coronary syndrome. Rupture
      prone plaques typically have a thin fibrous cap, numerous inflammatory cells, a
      substantial lipid core, and surprisingly few smooth muscle cells. Physical
      disruption of such a plaque allows circulating blood coagulation factors to meet
      with the highly thrombogenic material in the plaque's lipid core, thereby
      instigating the formation of a potentially occluding and fatal thrombus. Much
      evidence implicates inflammation in the thinning of the fibrous cap and the
      disruption of the vulnerable atherosclerotic plaque. Lipid lowering undisputedly
      reduces the incidence of acute coronary events. However, the hypothesis that the
      mechanism of event reduction involves regression of fixed stenoses has proved
      untenable. In 14 angiographic studies, treatment of abnormal lipid levels
      increased luminal diameter only modestly, in stark contrast to the resounding and
      consistent decrease in acute coronary events produced by lipid lowering.
      Therefore, we now believe that lipid-lowering treatments, such as statins, modify
      plaques qualitatively as much as quantitatively, reducing inflammation and
      stabilizing noncritically stenotic, yet vulnerable plaques. Studies in rabbits
      with diet-induced atherosclerosis have shown that reducing cholesterol
      consumption indeed decreases inflammation in atheroma and improves those features
      of plaques associated with stability.

PMID- 11595193
TI  - What is the role of intensive cholesterol lowering in the treatment of acute
      coronary syndromes?
AB  - Cholesterol lowering with statins reduces coronary events in a primary-prevention
      setting and in patients with stable coronary disease. However, where the risk of
      a coronary event is highest, in the early months after an episode of unstable
      angina or non-Q-wave infarction, the effect of statin therapy has not been
      evaluated until recently. The lack of an early benefit in the 3 main statin
      trials in stable coronary disease may have discouraged this type of
      investigation. Yet, evidence suggests that intensive cholesterol lowering can
      rapidly influence several mechanisms intimately related to the pathogenesis of
      acute coronary syndromes; specifically, improvement in endothelial function,
      decreased propensity for platelet thrombus formation, and reduced inflammation.
      Furthermore, 3 nonrandomized, observational studies have recently reported an
      improved outcome in statin-treated compared with untreated patients after acute
      coronary syndromes.

PMID- 11595194
TI  - Global risk assessment in the presymptomatic patient.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality, both in
      the United States and worldwide. It has become widely recognized that a high
      percentage of cardiovascular events, including sudden cardiac death, occur in
      previously asymptomatic individuals. Consequently, the primary prevention of
      cardiovascular disease, particularly coronary artery disease (CAD), is an
      important objective of modern health-care policy. To identify and target high
      risk individuals for lifestyle and therapeutic interventions, aggressive
      screening of the healthy population at risk of developing CAD (or other
      atherosclerotic disease) is necessary. Because of the complex and often
      synergistic relations between independent risk factors, it is also important that
      a multifactorial approach to the treatment of cardiovascular risk factors is
      adopted. Although treatment guidelines and goals for certain risk factors have
      been published by national and international organizations, recent evidence
      suggests that these recommendations are not always adopted in clinical practice.
      Therefore, considerable potential remains for primary care physicians to further
      reduce cardiovascular morbidity and mortality in presymptomatic individuals.

PMID- 11595195
TI  - United States Cholesterol Guidelines 2001: expanded scope of intensive low
      density lipoprotein-lowering therapy.
AB  - The new clinical guidelines of the US National Cholesterol Education Program
      (NCEP) were released in May 2001. These guidelines were published as the NCEP's
      Adult Treatment Panel (ATP) III report. They are derived from an extensive review
      of the emerging literature so as to provide an evidence-based report. Thanks to
      recent clinical trials of cholesterol-lowering therapy, it is possible to expand
      the scope of clinical management for both dietary and drug therapies. This
      expansion derives from a conclusive demonstration of efficacy, safety, and cost
      effectiveness of therapies. This article will review briefly the major features
      of ATP III.

PMID- 11595196
TI  - The use of electron-beam computed tomography as a tool for primary prevention.
AB  - Coronary artery disease (CAD) is the most common cause of death in the United
      States, and most acute CAD events occur unexpectedly in patients unaware of their
      condition. Consequently, attention has recently focused on the development of new
      technologies for the early detection of CAD, such as electron-beam computed
      tomography (EBCT). With EBCT imaging, the coronary artery tree is visualized
      noninvasively and vascular calcification, a marker of atherosclerotic disease, is
      easily detected and its extent quantified. Current research suggests that the
      presence of coronary artery calcification on a screening EBCT image provides
      relevant prognostic information for the development of future coronary events.
      Furthermore, preliminary evidence suggests that the use of EBCT to observe the
      progression of disease, as demonstrated by changes in the coronary calcium burden
      on sequential studies, is a viable and exciting new application. The Beyond
      Endorsed Lipid Lowering with EBCT Scanning (BELLES) trial will use EBCT to
      compare the effects of 12 months of treatment with aggressive or moderate statin
      therapy on the progression of coronary atherosclerosis.

PMID- 11595197
TI  - Cerebrovascular disease and statins: a potential addition to the therapeutic
      armamentarium for stroke prevention.
AB  - Cerebrovascular disease is the leading cause of disability in Western societies.
      In the United States, it has been estimated that a stroke occurs every 53
      seconds. Consequently, the societal costs attributable to cerebrovascular disease
      are immense and encourage the medical community to seek new therapies that can
      reduce stroke's frequency and impact. Although serum lipid levels have not been
      shown to act as a surrogate marker for stroke, in landmark lipid-lowering trials,
      statin therapy has been associated with reductions in the incidence of ischemic
      stroke in patient populations with manifest ischemic heart disease. This
      observation is supported by a recently published meta-analysis of statin trials
      that reported an average reduction of about 30% in the incidence of
      cerebrovascular disease. However, to date, statin studies have only been
      conducted in patients with, or at high risk for coronary artery disease, who are
      not truly representative of the overall stroke population. The ongoing Stroke
      Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL) trial has been
      designed to prospectively evaluate the benefits of aggressive lipid-lowering
      therapy on cerebrovascular events in patients who have had a previous stroke or
      transient ischemic attack, but who have no prior history of coronary artery
      disease.

PMID- 11595198
TI  - Insulin resistance syndrome and type 2 diabetes mellitus.
AB  - Patients with type 2 diabetes mellitus have an elevated risk of morbidity and
      mortality from cardiovascular disease. This risk is partly attributable to an
      increased prevalence of classic coronary artery disease risk factors and partly
      because of hyperglycemia itself and a highly atherogenic lipid profile. The
      altered composition of lipoproteins and lipids in type 2 diabetic patients,
      termed diabetic dyslipidemia, is characterized by: (1) elevated levels of
      triglyceride; (2) normal levels of total and low-density lipoprotein cholesterol
      (LDL-C); (3) reduced levels of high-density lipoprotein cholesterol (HDL-C); (4)
      elevated levels of apolipoprotein B; (5) a preponderance of small, dense LDL
      particles; and (6) increased levels of cholesterol-rich very-low-density
      lipoprotein. In most cases, diabetic dyslipidemia is preceded by hyperinsulinemia
      resulting from insulin resistance. Because patients with type 2 diabetes and
      insulin resistance are at a markedly increased risk of atherosclerosis, and
      because strict control of glycemia has proved beneficial in reducing
      microangiopathy but not macroangiopathy, treatment of diabetic dyslipidemia
      should be aggressive. Target levels have, therefore, been set at <2.6 mmol/L (100
      mg/dL) for LDL-C, <2.3 mmol/L [200 mg/dL] for triglycerides, and >1.15 mmol/L (45
      mg/dL) for HDL-C. Trial data suggest that these target levels are likely to be
      achieved with statins, if necessary, in combination with fibrates or nicotinic
      acid derivatives. Furthermore, in large-scale clinical trials (eg, Scandinavian
      Simvastatin Survival Study [4S] and the Cholesterol and Recurrent Events [CARE]
      study), it has been demonstrated that lipid lowering can appreciably reduce
      cardiovascular events in diabetic patients.

PMID- 11595199
TI  - Systemic atherosclerosis risk and the mandate for intervention in atherosclerotic
      peripheral arterial disease.
AB  - Peripheral arterial disease (PAD), characterized by obstruction of the arteries
      in the lower limbs, is an important manifestation of atherosclerosis. There are
      >10 million individuals with PAD in the United States alone, and as the overall
      population in developed countries ages, PAD will become increasingly prevalent.
      Many individuals with PAD are asymptomatic and therefore remain undiagnosed and
      untreated. Most patients with PAD are at high risk for having a serious coronary
      or cerebrovascular event. Even for patients in whom symptoms, such as leg pain,
      are clearly evident, current treatment strategies tend to ignore the systemic
      nature of the disease and do not reduce overall atherosclerotic risk. Proven
      medical treatment options for patients with intermittent claudication include
      smoking cessation, exercise, and cilostazol. Pentoxifylline appears marginally
      effective. Several novel therapies for PAD are currently under investigation. Of
      particular interest are the observations from some studies that show that lipid
      lowering therapy might be of benefit to PAD patients. The results of 2 ongoing
      prospective trials of dyslipidemic therapy in claudicants should further clarify
      the benefits of reducing serum lipid levels in patients with established PAD.

PMID- 11595200
TI  - Women and cardiovascular risk.
AB  - Cardiovascular disease mortality rates have decreased in men during the past 20
      years, but have steadily increased in women. In the United States, >500,000 women
      die of coronary artery disease (CAD) every year. Although many factors can
      influence an individual's risk for CAD, some factors are unique to women,
      including reproductive status. Menopause is associated with significant
      elevations in serum cholesterol levels and a 3-fold increase in the risk of CAD.
      It has been suggested that these changes result from a reduction in the level of
      estrogen. However, recent data from prospective clinical trials have not found
      any evidence that hormone replacement therapy protects against cardiovascular
      disease. On the other hand, several studies have shown that, in women, lipid
      lowering with statin therapy can reduce coronary events. On the strength of these
      findings, the Beyond Endorsed Lipid Lowering with Electron-Beam Computed
      Tomography Scanning (BELLES) trial-a 1-year, multicenter, randomized, double
      blind, parallel-group study-has been specifically designed to determine the
      benefits of aggressive statin therapy on the progression of atherosclerosis in
      postmenopausal women.

PMID- 11595201
TI  - Comparison of reactive processes in the rat brain elicited by xenotransplantation
      of nervous tissues of chicken or pulmonate snail.
AB  - It is known that a histocompatibility system is not developed to the same extent
      in lower invertebrates as in vertebrate animals. We assumed that the xenografts
      from the newborn invertebrate nervous system would not exert destructive effects
      on the brain of the vertebrate recipient even without immunosuppressive therapy.
      In search of brain xenografts (XG) capable to survive in the brain of a recipient
      without intensive immunosuppression, we transplanted ganglia of terrestrial
      snails into the rat brain. We compared effects of transplantation of the XG taken
      from anterior brain of the 18-day embryo chicken (XGC) and from ganglia of a
      newborn terrestrial pulmonate snail (Helix aspersa L., XGSn). Part of the XGSn
      were stained by vital fluorescent dyes Bisbenzimid or Fast Blue before grafting.
      The XGSn were implanted into the neocortex parenchyma in each hemisphere. Rat
      brains with the XGC were examined 5 days after, and brains with the XGSn - 5 and
      28 days after the transplantation. Nonstained sections with the XGSn labeled with
      fluorescent dyes prior to transplantation were investigated in fluorescent
      microscope and stained later with tionin and cresyl-violet. Quantitative
      videoimage analysis of lymphocyte aggregations, reactive gliosis, morphology of
      the XG areas, and implantation trace was performed. It was found that the XGSn
      transplantation did not elicit in the rat brain an intensive immunological
      conflict 5 and 28 days after transplantation. In contrast, the XGC rapidly
      elicited a strong immune response resulting in massive obliterations in the rat
      brain and were rejected in 5 days. Labeled snail glia and vessels were observed
      in the stained XGSn 28 days after transplantation by fluorescence imaging.
      Putative snail vessels grew into the rat brain from the place of snail tissue
      transplantation serving the humoral integration of the XG and the host brain.
      Migration of molluscan glial cells was observed in the brain of recipients.

PMID- 11595202
TI  - Cortical devascularization: quantitative diffusion weighted magnetic resonance
      imaging and histological findings.
AB  - This study investigates the development of a small focal cortical lesion produced
      in a model of brain injury. Two approaches were chosen: diffusion weighted
      magnetic resonance imaging (DWI) and histology. DW images were collected before
      devascularization and at 0.5, 1, 2, 3, 5, 7 and 14 days after treatment. Apparent
      diffusion coefficient (ADC) maps were calculated from the DW images to quantify
      lesion development. As a second measure of injury, tissue morphology was analyzed
      using cresyl violet histochemistry. A significant reduction in ADC values within
      the cortex below the injury site by 0.5 days after surgery was observed. Between
      5 and 14 days the ADC values recovered to control levels. ADC changes were also
      observed in the contralateral cortex at 0.5, 1 and 5 days. The decrease in ADC
      observed at the early time points suggested cytotoxic edema, whereas the recovery
      to control levels at later time points suggested infarct formation. This model of
      brain injury resulted in progressive but relatively slow formation of a pan
      necrotic infarct within 14 days. In particular, substantial amounts of cell death
      were not observed until 2 days after surgery. Overall, the quantitative and
      histological measures of this lesion are consistent with those observed for an
      ischemic type of injury, however, the time course of these lesions' development
      are consistent with other models of traumatic brain injury. Our data demonstrates
      that DWI is a highly sensitive metric for ischemic-type damage that results from
      brain injury.

PMID- 11595203
TI  - Food-related gastrointestinal signals activate caudal brainstem neurons
      expressing both NMDA and AMPA receptors.
AB  - Vagal mechano- and chemosensors in the gastrointestinal tract and the portal
      hepatic axis signaling the arrival of nutrients are major determinants of the
      satiation process. Although glutamate and its various receptor subtypes have been
      shown to transmit gustatory and cardiovascular sensory information at the level
      of the solitary nucleus (nucleus tractus solitarius; NTS), their involvement in
      the transmission of gastrointestinal satiety signals is not clear.
      Gastrointestinal sensors were stimulated by gastric balloon distension or by
      intraduodenal infusion of either linoleic acid or glucose in chronically
      catheterized, non-anesthetized rats, leading to activation of second order
      neurons in the NTS as detected by c-Fos immunohistochemistry. Subsequent (double)
      immunohistochemistry for either NMDA or AMPA glutamate receptors was used to
      determine the percentage of activated neurons expressing a particular receptor
      subtype. Gastric distension and duodenal nutrient stimuli produced slightly, but
      significantly different patterns of c-Fos induction in the dorsal vagal complex.
      Expression of NMDA receptors, as detected by a NR2ab subunit-specific antibody,
      was abundant throughout the dorsal medulla. The percentage of neurons in the NTS
      activated by gastric distension (63.9+/-2.9%), linoleic acid (62.8+/-1.4%), and
      glucose (64.1+/-1.4%), expressing NMDA receptor was similar. Expression of AMPA
      receptors, as detected by a GLUR2/3 subunit-specific antibody, was equally
      abundant throughout the dorsal medulla. Again, the percentage of activated
      neurons expressing GLUR2/3 was similar for the gastric distension (59.8-65.6%)
      and duodenal linoleic acid (60.6-67.0%) stimuli, and for the various subnuclei of
      the NTS. Finally, GLUR1-specific immunoreactivity was much less abundant, with
      only a small percentage of distension-activated (4.4+/-0.4%) and linoleic acid
      activated (5.1+/-0.4%) neurons expressing this receptor subunit. The results
      suggest a widespread, general involvement of both NMDA and AMPA receptors in
      primary afferent signal transmission at the level of the NTS, with no
      differential recruitment of the examined receptor subtypes by the different
      gastrointestinal sensory stimuli. This may indicate a high degree of convergence
      among sensory signals, or alternatively, the presence of other transmission
      systems such as peptides referring sensory specificity to second order neurons.

PMID- 11595204
TI  - Endogenous morphine and codeine. Possible role as endogenous anticonvulsants.
AB  - Exogenously administered morphine can have both convulsive or anticonvulsive
      effects, depending on the dose and species. The levels of the endogenous opiate
      alkaloids morphine and codeine were significantly elevated in specific rat brain
      regions by the convulsive drug, pentylenetetrazole, as well as by the
      anticonvulsant drugs, carbamazepine and phenytoin. Morphine and codeine levels in
      peripheral tissues (heart, lung, spleen and adrenal) were unaffected by these
      drugs. Maximal increases in morphine levels were seen in the hypothalamus and
      striatum (2-10-fold), while lesser increases occurred in the midbrain and brain
      stem (2-4-fold). Codeine levels were also markedly increased in hypothalamus (5
      10 fold), In contrast to morphine, codeine levels were also increased in the
      hippocampus (2-10-fold), but were unchanged in the striatum. These studies
      suggest that the endogenous alkaloids morphine and codeine are involved in the
      modulation of convulsions and that morphine and/or codeine may act as an
      endogenous anticonvulsant.

PMID- 11595205
TI  - Development of purinergic sensitivity in sensory neurons after peripheral nerve
      injury in the rat.
AB  - Purinoceptors are present in the cell bodies as well as in both peripheral and
      central terminals of many sensory neurons, where they may play a role in sensory
      transmission, including pain. After peripheral nerve injury at the spinal nerve
      level, some axotomized afferent neurons develop ongoing discharges (ectopic
      discharges) that originate in the dorsal root ganglion (DRG). In the present
      study, we attempted to determine whether or not purinergic sensitivity develops
      in injured sensory neurons which display ectopic discharges, as well as in silent
      units. The L(4) and L(5) spinal nerves were ligated in Sprague-Dawley rats. Four
      to 21 days after the surgery, the DRGs with attached dorsal roots and spinal
      nerves were removed and ectopic discharges were recorded from teased dorsal root
      fascicles using an in vitro recording set-up. The results showed that 75.6 and
      65.1% of the chronically axotomized DRG neurons displaying ectopic discharges
      enhanced their activity after application of adenosine 5'-triphosphate (ATP, 1
      mM) or alpha,beta-methylene ATP (mATP, 100 microM), respectively. In addition,
      application of these purinoceptor agonists evoked activity in 7 of 28 axotomized
      DRG neurons, which did not show ongoing discharges. In contrast, only 1 of 34 DRG
      neurons acutely isolated from normal rats (no previous spinal nerve ligation)
      responded to either mATP or ATP. In most of the tested units, mATP-induced
      enhancement of ectopic discharges was blocked by non-specific P2X receptor
      antagonists, PPADS or suramin. The data from the present study suggest that
      purinergic sensitivity develops in DRG neurons after chronic axotomy and that
      this purinergic sensitivity is likely to be mediated by P2X purinoceptors. This
      acquired purinergic sensitivity may play an important functional role in the
      enhancement of ectopic discharges and exacerbation of pain upon sympathetic
      activation in the neuropathic pain state.

PMID- 11595206
TI  - Anxiolytic actions of the substance P (NK1) receptor antagonist L-760735 and the
      5-HT1A agonist 8-OH-DPAT in the social interaction test in gerbils.
AB  - The gerbil social interaction test has previously detected anxiolytic effects of
      nicotine and diazepam. In the present study, the high affinity substance P
      (NK(1)) receptor antagonist L-760735 (3 mg/kg) significantly increased the time
      spent in social interaction, whereas its low affinity analogue L-781773 (3 mg/kg)
      was without effect. Diazepam (0.1 mg/kg) and the 5-HT(1A) receptor agonist 8-OH
      DPAT (0.003 and 0.01 mg/kg) also increased social interaction, whereas an acute
      dose of the selective serotonin re-uptake inhibitor fluoxetine (10 mg/kg)
      decreased the time spent in social interaction. Diazepam (0.1 mg/kg)
      significantly increased locomotor activity, but this effect was independent of
      the increase in social interaction. The other drugs tested were without effect on
      locomotor activity. The present findings suggest that the gerbil social
      interaction may well provide a useful assay for detecting both anxiolytic and
      anxiogenic compounds, and suggests that the high affinity NK(1) receptor
      antagonist L-760735 may prove to be useful as an anxiolytic therapy.

PMID- 11595207
TI  - Ethanol administration potentiates cocaine-induced dopamine levels in the rat
      nucleus accumbens.
AB  - Ethanol and cocaine are frequently co-abused, and the drug combination has been
      reported to produce an increased and prolonged subjective euphoria as compared to
      when either drug is administered alone. Acute administration of ethanol or
      cocaine increases the extracellular dopamine (DA) concentration in the nucleus
      accumbens (NAcc), a terminal region of the mesolimbic dopaminergic pathway. In
      the present study, the effects of separate and concurrent administration of
      cocaine and ethanol on DA concentrations in the NAcc were studied in rats
      pretreated with ethanol. Four groups of rats received either ethanol (2 g/kg,
      i.p.) or saline twice daily for 6 consecutive days. Thereafter, rats were given
      injections of saline or cocaine for another 2 days (i.e. treatment days 7 and 8)
      using a 'binge' administration pattern (three i.p. injections of 15 mg/kg each
      with 1-h interval starting 40 min after the first of the two daily doses of
      ethanol/saline). Stereotypic behavior was scored after each 'binge' of cocaine or
      saline on days 7 and 8. The DA and DA metabolite concentrations were measured
      using microdialysis on day 8. Ethanol enhanced the effect of cocaine on DA
      concentration in the NAcc as compared to a single administration of cocaine. The
      DA levels increased and reached their maximum values within 20-40 min after the
      cocaine administration, then gradually declined until the next injection 1-h
      later. Cocaine-induced stereotypic behavior was significantly increased in both
      saline and ethanol pretreated groups, though there was no significant difference
      between the two groups. The results of this study suggest that the enhanced DA
      transmission may be related to the experience produced by concurrent abuse of
      ethanol and cocaine in humans.

PMID- 11595208
TI  - Tongue and jaw muscle activities during chewing and swallowing in freely behaving
      rabbits.
AB  - To study the function of the tongue and the coordination among jaw, tongue, and
      hyoid muscles during chewing and swallowing, we recorded the electromyographic
      activities from the masseter (Mas), digastric (Dig), mylohyoid (Myl), thyrohyoid
      (Thy), genioglossus (Gg) and styloglossus (Sg) muscles as well as jaw movement
      trajectories in the freely behaving rabbit. Three phases were identified in the
      chewing cycle (fast- and slow-closing and opening phases). The Gg (main tongue
      protruder) was active synchronously with the Dig during opening. The Sg (tongue
      retractor) showed two peaks in each cycle, one in the opening phase and the other
      in the closing phase. The latter may have a role in retracting the tongue during
      jaw closing. The co-contraction of the antagonists (i.e. Gg and Sg) during
      opening may contribute to shape the tongue to be appropriate to gather the
      foodstuff. In the swallowing cycle, five phases were identified, two in the
      closing phase and three in the opening phase. Regression analysis revealed that
      swallowing cycles had a longer cycle duration than that of the chewing cycles due
      to an extra phase (a pause) inserted in the opening phase, where there was a
      small co-activation in the jaw opening and closing muscles. The findings suggest
      that the swallowing center affects masticatory center in the central nervous
      system, and may also support the view that the masticatory burst timing begins
      with the Dig activities in the middle of the opening phase.

PMID- 11595209
TI  - Parathyroid hormone-related protein (PTHrP) induction in reactive astrocytes
      following brain injury: a possible mediator of CNS inflammation.
AB  - PTHrP, a peptide induced in parenchymal organs during endotoxemia and in the
      synovium in rheumatoid arthritis, has recently been shown to be expressed in
      immature or transformed human astrocytes, but not in normal cells. This finding
      has led us to postulate that PTHrP might also be induced in reactive astrocytes
      in inflamed brain and, thus, act as a mediator of CNS inflammation. To test this
      hypothesis, PTHrP expression was examined following cortical stab wound injury in
      rats, a classical model of reactive gliosis. To determine whether PTHrP was
      induced in glia by TNF-alpha, a known mediator of inflammation in brain and of
      PTHrP induction in peripheral tissues, and to determine whether PTHrP, in turn,
      mediated inflammatory changes in glia, in vitro studies with rat astrocytes and
      glial-enriched mixed brain cells were also undertaken. Consistent with previous
      reports of PTHrP expression in normal brain, neurons were the primary site of
      immunoreactive PTHrP expression in the injured cortex 1 day after stab wound
      injury. Over the subsequent 3 days, specific immunostaining for PTHrP and for
      GFAP, a marker of reactive astrocytes, appeared in reactive astrocytes at the
      wound edge and in perivascular astrocytes, reaching a maximum level of expression
      at the last time point examined (day 4). TNF-alpha induced PTHrP expression in
      astrocyte and glial-enriched brain cells in vitro, suggesting that this pro
      inflammatory peptide was a possible mediator of PTHrP expression in CNS
      inflammation. PTHrP(1-34) acted in an additive fashion with TNF-alpha to induced
      astrocyte expression of IL-6, a cytokine with demonstrated neuroprotective
      effects. Astrocyte proliferation was inhibited by PTHrP(1-34) and PTHrP(1-141),
      acting via a PTH/PTHrP receptor cAMP signaling pathway. These studies suggest
      that PTHrP, analogous to its regulatory functions in other non-CNS models of
      inflammation, may be an important mediator of the inflammatory response in brain.

PMID- 11595210
TI  - Long-term neuroprotective effect of inhibiting poly(ADP-ribose) polymerase in
      rats with middle cerebral artery occlusion using a behavioral assessment.
AB  - Poly(ADP-ribose) polymerase (PARP) can initiate an energy-consuming and
      inefficient repair cycle following cerebral ischemia/reperfusion by transferring
      ADP ribose units to nuclear proteins eventually leading to cellular dysfunction
      and neuronal death. 3-Aminobenzamide (3-AB) is a selective inhibitor of PARP that
      can significantly reduce brain damage after focal ischemia in rats and displays a
      low toxicity in vivo. The goals of this study were to determine if inhibiting
      PARP with 3-AB has a long-term neuroprotective effect and if functional outcome
      improves in rats following focal ischemia and treatment with 3-AB. Focal ischemia
      was induced by a 2-h occlusion of the middle cerebral artery (MCA), using an
      intraluminal filament. Motor functions were evaluated from 5 to 28 days after
      reperfusion in four groups of rats: stroke without treatment; stroke treated with
      3-AB at doses of 15 mg/kg, stroke treated with 3-AB at doses of 55 mg/kg; and the
      non-ischemic control rats. Functional behaviors were tested by a series of motor
      function tasks (foot placing, parallel bar crossing, rope and ladder climbing),
      as well as a neurological examination. Infarct volume of stroke brain in the same
      rat was determined by Nissl staining 28 days after surgery. Comparison of the
      untreated stroke group (n=11) and the treated stroke groups indicates that
      impairment of motor function was significantly (P<0.001) reduced by
      administration of 3-AB at doses of 15 mg/kg (n=9) or 55 mg/kg (n=10).
      Neurological outcome was also improved significantly (P<0.001). Infarct volume
      was significantly (P<0.01) reduced in both treated groups. Long-term
      neuroprotection following ischemia/reperfusion injury to the brain can be
      obtained by administration of a PARP inhibitor. The motor tests employed in this
      study can be used as sensitive, objective and reproducible measurements of
      functional impairment in rats following an ischemic stroke.

PMID- 11595211
TI  - On the antinociceptive effect of fluoxetine, a selective serotonin reuptake
      inhibitor.
AB  - Antidepressant drugs are reported to be used as co-analgesics in clinical
      management of migraine and neuropathic pain. The mechanism through which they
      alleviate pain remains unknown. The present study explores the possible mechanism
      of a selective serotonin reuptake inhibitor (SSRI) fluoxetine-induced
      antinociception in animals. Acetic acid-induced writhing, hot plate and tail
      flick test were used to assess fluoxetine-induced antinociception. Fluoxetine (5
      20 mg kg(-1), i.p.) produced a significant and dose-dependent antinociceptive
      effect against acetic acid-induced writhing in mice. Fluoxetine (20 mg kg(-1))
      also exhibited antinociceptive effect in tail flick as well as hot plate assays.
      Further, i.c.v. administration of fluoxetine showed significant antinociception
      against writhing test in rats. However, fluoxetine (1 microg/10 microl/rat,
      i.c.v.) did not exhibit any antinociceptive effect in serotonin-depleted animals.
      Further, pindolol (10 mg kg(-1), i.p.) enhanced fluoxetine-induced
      antinociceptive effect. The antinociceptive effect of fluoxetine was sensitive to
      blockade by naloxone (5 mg kg(-1), i.p.) and naltrexone (5 mg kg(-1), i.p.).
      These data suggest that fluoxetine-induced antinociception involves both central
      opioid and the serotoninergic pathways.

PMID- 11595212
TI  - Correlation between hippocampal BDNF mRNA expression and memory performance in
      senescent rats.
AB  - Brain-derived neurotrophic factor (BDNF) has been suggested to be involved in
      memory processes. In the present study, the association between memory impairment
      at senescence and BDNF expression in the hippocampus was studied in 30-32-month
      old Brown Norway rats, which had been maternally deprived early in life. These
      animals display a bimodal distribution in their spatial learning ability: rats
      are either non-impaired or impaired. BDNF mRNA expression in the hippocampus was
      compared between non-impaired and impaired rats. We measured BDNF mRNA expression
      in the hippocampus 3 h after training in the Morris water maze ('post-training')
      and at 1 month after training ('basal'). Non-impaired performers displayed a
      higher post-training BDNF mRNA level in the CA1 region than impaired rats. In
      addition, only in the non-impaired performers post-training BDNF mRNA levels in
      CA1 and dentate gyrus were increased as compared to basal levels. Thus, we have
      demonstrated that in senescent rats, hippocampal BDNF expression in response to
      water maze training is associated with memory performance.

PMID- 11595213
TI  - Intracerebroventricular injection of exendin (5-39) increases food intake of
      layer-type chicks but not broiler chicks.
AB  - To clarify the involvement of endogenous glucagon-like peptide-1 (GLP-1) on
      feeding in chicks, we examined the central effect of GLP-1 antagonist, exendin (5
      39) on food intake. Intracerebroventricular co-injection of exendin (5-39) with
      GLP-1 attenuated the anorexigenic effect of GLP-1 in layer-type chicks.
      Furthermore, exendin (5-39) enhanced food intake of layer-type chicks under ad
      libitum feeding. However, this effect was not observed in broiler chicks.
      Therefore, endogenous GLP-1 may be important in the regulation of feeding in
      layer-type chicks but not in broiler chicks.

PMID- 11595214
TI  - Neurokinin-1 receptor immunoreactivity in hypotension sensitive sympathetic
      preganglionic neurons.
AB  - Substance P activation of neurokinin-1 (NK1) receptors on spinal sympathetic
      preganglionic neurons (SPN) influences blood pressure. We identified SPN likely
      to subserve the baroreceptor reflex and established if these neurons showed NK1
      receptor-immunoreactivity. Nitroprusside (NP) infusion or inferior vena cava
      (IVC) constriction activated similar numbers of SPN. Of these, about 40% were NK1
      receptor-immunoreactive after NP infusion, but only about 20% were NK1 receptor
      immunoreactive after IVC constriction. The distribution of Fos/NK1 receptor SPN
      suggested that substance P may preferentially target sympathoadrenal SPN.

PMID- 11595215
TI  - Effects of serotonin synthesis blockade on interleukin-1 beta action in the brain
      of rats.
AB  - The ability of the brain serotonergic system to mediate the effects of
      interleukin-1beta (IL-1beta) was investigated. Intracerebroventricular
      administration of IL-1beta induced a significant pyrogenic reaction, depression
      in social behaviour, loss of body weight and reduced food intake in rats. Pre
      treatment with p-chlorphenylalanine, an inhibitor of serotonin synthesis, blocked
      the IL-1beta-induced decrease in food intake and loss of body weight, but failed
      to alter the temperature increase and the decrease in communicative activity.

PMID- 11595216
TI  - Concurrent release of ATP and substance P within guinea pig trigeminal ganglia in
      vivo.
AB  - Neurons within sensory ganglia have been proposed to communicate via non-synaptic
      release of a diffusible chemical messenger, but the identity of the chemical
      mediator(s) remains unknown [J. Neurosci. 16 (1996) 4733-4741]. The present study
      addressed the possibility of co-released ATP and substance P (SP) within sensory
      ganglia to further advance the hypothesis of non-synaptic communication between
      sensory neurons. Microdialysis probes inserted into trigeminal ganglia (TRGs) of
      anesthetized guinea pigs were perfused with artificial cerebrospinal fluid and
      the collected perfusate analyzed for ATP and SP content using the firefly
      luciferin-luciferase (L/L) assay and radioimmunoassay, respectively. Significant
      reversible increases in ATP and SP levels were observed after infusion of 100 mM
      KCl or 1 mM capsaicin. Ca(2+)-free ACSF produced an eightfold increase in ATP
      levels, interpreted as a decrease in activity of Ca(2+)-dependent ecto
      nucleotidases that degrade ATP. In contrast, KCl-induced release of ATP in the
      presence of normal Ca(2+) was blocked by Cd(2+), a voltage-gated Ca(2+) channel
      blocker, illustrating Ca(2+)-dependence of evoked ATP release. Since ganglionic
      release of ATP could arise from several neuronal and non-neuronal sources we
      directly tested acutely dissociated TRG neuron somata for ATP release. Neuron
      enriched dissociated TRG cells were plated onto glass tubes and tested for ATP
      release using the L/L assay. Robust ATP release was evoked with 5 microM
      capsaicin. These data suggest that ATP is released concurrently with SP from the
      somata of neurons within sensory ganglia.

PMID- 11595217
TI  - Synthesis and NMR spectroscopy of nine stereoisomeric 5,7-diacetamido-3,5,7,9
      tetradeoxynon-2-ulosonic acids.
AB  - Derivatives of 5,7-diamino-3,5,7,9-tetradeoxynon-2-ulosonic acids are essential
      constituents of some bacterial polysaccharides and glycoproteins. In order to
      establish reliably the configuration of the natural sugars, nine stereoisomeric
      5,7-diacetamido-3,5,7,9-tetradeoxynon-2-ulosonic acids were synthesized,
      including di-N-acetyl-legionaminic and -pseudaminic acids (the D-glycero-D
      galacto and L-glycero-L-manno isomers, respectively) and their isomers at C-4, C
      5, C-7, and C-8 having the L-glycero-D-galacto, D-glycero-D-talo, L-glycero-D
      talo, D-glycero-L-altro, L-glycero-L-altro, D-glycero-L-manno, and L-glycero-L
      gluco configurations. Synthesis was performed by condensation of 2,4-diacetamido
      2,4,6-trideoxy-L-gulose, -D-mannose, -D-talose, and -L-allose with oxalacetic
      acid under basic conditions, the reaction of the last two precursors being
      accompanied by epimerisation at C-2. The 1H and 13C NMR data of the synthetic
      compounds are discussed. Acetylated methyl esters of the C-7 and C-8 isomeric
      nonulosonic acids were prepared and used for analysis of the side-chain
      conformation by NMR spectroscopy.

PMID- 11595218
TI  - Synthesis of gallotannins.
AB  - As a contribution to the synthesis of gallotannins, four O-galloyl-D-glucoses (3
      O-, 6-O-, 3,6-di-O-, 3,4,6-tri-O-galloyl-D-glucose) have been prepared by the
      reaction of tri-O-benzylgalloyl chloride and partially protected glucose
      derivatives (1,2-O-, and 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose),
      followed successively by catalytic debenzylation (Pd-C) and controlled acid
      hydrolysis. Their structures were established from their behavior on TLC and from
      their 1H and 13C NMR spectra.

PMID- 11595219
TI  - A rapid and sensitive procedure for determination of 5-N-acetyl neuraminic acid
      in lipopolysaccharides of Haemophilus influenzae: a survey of 24 non-typeable H.
      influenzae strains.
AB  - In view of the importance of 5-N-acetyl neuraminic acid in bacterial
      pathogenesis, a sensitive, reproducible and reliable method for the determination
      of 5-N-acetyl neuraminic acid levels in lipopolysaccharide (LPS) is described and
      applied to 24 different non-typeable Haemophilus influenzae (NTHi) strains. The
      method involves analysis by high-performance anion-exchange chromatography with
      pulsed amperometric detection (HPAEC-PAD) of terminal 5-N-acetyl neuraminic acid
      residues released by neuraminidase treatment of O-deacylated LPS. The procedure
      is relatively fast and the instrumental effort is moderate. The results of the
      procedure were compared with data obtained by 1H NMR and electrospray ionisation
      mass spectrometry (ESI-MS). The analysis of LPS from 24 NTHi strains showed that
      5-N-acetyl neuraminic acid was found to be a common constituent of LPS in NTHi.
      Only one strain (NTHi 432) did not show any sialylation. Molar ratios (LPS/5-N
      acetyl neuraminic acid) ranged between 5/1 and 500/1. Several strains in which no
      5-N-acetyl neuraminic acid could be determined by other methods including 1H NMR
      and ESI-MS were shown to contain 5-N-acetyl neuraminic acid by this HPAEC-PAD
      procedure. The method was applied to determine levels of terminal 5-N-acetyl
      neuraminic acid in LPS from NTHi strains grown under different conditions and
      mutant strains containing inactive LPS biosynthetic genes.

PMID- 11595220
TI  - Modeling of deoxy- and dideoxyaldohexopyranosyl ring puckering with MM3(92).
AB  - Extensive variations of the ring structures of three deoxyaldohexopyranoses, L
      fucose, D-quinovose, and L-rhamnose, and four dideoxyaldohexopyranoses, D
      digitoxose, abequose, paratose, and tyvelose, were studied by energy minimization
      with the molecular mechanics algorithm MM3(92). Chair conformers, 4C(1) in D
      quinovose and the equivalent 1C(4) in L-fucose and L-rhamnose, overwhelmingly
      dominate in the three deoxyhexoses; in the D-dideoxyhexoses, 4C(1) is again
      dominant, but with increased amounts of 1C(4) forms in the alpha anomers of the
      three 3,6-dideoxyhexoses, abequose, paratose, and tyvelose and in both alpha and
      beta anomers of the 2,6-dideoxyhexose D-digitoxose. In general, modeled proton
      proton coupling constants agreed well with experimental values. Computed anomeric
      ratios strongly favor the beta configuration except for D-digitoxose, which is
      almost equally divided between alpha and beta configurations, and L-rhamnose,
      where the beta configuration is somewhat favored. MM3(92) appears to overstate
      the prevalence of the equatorial beta anomer in all three deoxyhexoses, as
      earlier found with fully oxygenated aldohexopyranoses.

PMID- 11595221
TI  - Combinatorial evaluation of the chiral discrimination of permethylated
      carbohydrates using fast-atom bombardment mass spectrometry.
AB  - The chiral discrimination abilities of several variously permethylated
      carbohydrates toward various amino acid 2-propyl esters were combinatorially
      evaluated from the relative peak intensity of the 1:1 diastereomeric complex ions
      with the deuterium-labeled L-amino acid 2-propyl ester protonated ion and with
      the unlabeled D-amino acid 2-propyl ester protonated ions in FAB mass
      spectrometry. The chiral discrimination abilities evaluated using FAB mass
      spectrometry approximately corresponded to the ratio of the association constants
      (K(R)/K(S)) toward each enantiomer in the solution. Therefore, this evaluation
      method is very useful for the screening of the chiral discrimination abilities of
      carbohydrates and their derivatives.

PMID- 11595222
TI  - Synthesis and biological activity of 4',8-dihydroxyisoflavon-7-yl D
      hexopyranosides.
AB  - Four 4',8-dihydroxyisoflavon-7-yl hexopyranoside derivatives having an aglycon
      part of A-76202 were synthesized, and their biological activities were evaluated
      toward rat liver alpha-glucosidase. However, the activities were disappointing.

PMID- 11595223
TI  - Structural analysis of the core region of the lipopolysaccharides from eight
      serotypes of Klebsiella pneumoniae.
AB  - The core regions of the lipopolysaccharides (LPS) from Klebsiella pneumoniae
      serotypes O1, O2a, O2a,c, O3, O4, O5, O8, and O12 were analysed using NMR
      spectroscopy, ESI-MS spectroscopy, and chemical methods. All the LPSs had similar
      core structures, as shown below, differing only in the number and position of
      beta-D-galacturonic acid substituents: [carbohydrate structure: see text] where P
      is H or alpha-Hep, J, K is H or beta-GalA. LPS from all serotypes contained
      varying proportions of structures having additional or missing phosphate
      substituents. The core from serotype O1 contained a minor amount of a previously
      described variant with alpha-DD-Hep-(1-->2)-alpha-DD-Hep-(1-->6)-alpha-GlcN-(1-->
      replacing the alpha-Hep-(1-->4)-alpha-Kdo-(2-->6)-alpha-GlcN-(1--> component.

PMID- 11595224
TI  - A water-soluble galactomannan from the seeds of Phoenix dactylifera L.
AB  - A water-soluble polysaccharide, isolated from the seeds of dates, has been
      investigated using methylation, periodate and CrO(3) oxidation, NMR spectroscopy,
      and reaction with Bandeiraea simplicifolia lectin and alpha-D-galactosidase. The
      polysaccharide consists of a backbone composed of (1-->4)-beta-D-mannopyranosyl
      residues and carries a single (1-->6)-alpha-linked D-galactopyranosyl residue.

PMID- 11595226
TI  - Unique aspects of mitochondrial biogenesis in trypanosomatids.
AB  - Mitochondrial biogenesis consists of the sum of all processes required for the
      formation of the mitochondrial membranes as well as the soluble compartments they
      contain. Furthermore, it includes the replication of the mitochondrial genome and
      correct segregation of the organelles during cell division. Mitochondrial
      proteins come from two sources, a limited but essential set of inner membrane
      proteins is encoded by the mitochondrial genome, whereas the large majority (90
      95%) is derived from nucleus-encoded genes and are posttranslationally imported
      into the organelle. Trypanosomatids belong to the earliest diverging branches of
      the eukaryotic evolutionary tree which have mitochondria. This is reflected in
      the organisation of their mitochondrial DNA that consists of a network of two
      classes of topologically interlocked circular DNA molecules as well as many
      unique features in their mitochondrial biogenesis. The proteins encoded on the
      mitochondrial genome are conventional for a mitochondrial genome, their
      expression, however, involves a complex series of processes. Many genes represent
      incomplete open reading frames and their primary transcripts have to remodelled
      by RNA editing to convert them into translatable mRNAs. RNA editing is mediated
      by small mitochondria-encoded transcripts, the guide RNAs, and is in that form
      specific for trypanosomatids and closely related organisms. Mitochondrial
      translation is also unconventional. No tRNA genes are encoded on the
      mitochondrial genome. Instead, mitochondrial protein synthesis functions
      exclusively with imported cytosolic, eukaryotic-type tRNAs. The composition of
      mitochondrial ribosomes is also unusual in that they contain the smallest known
      rRNAs. They are about 30% shorter than the already much reduced rRNAs in human
      mitochondria. Furthermore, the topological organisation of the mitochondrial
      genome requires an elaborate replication machinery involving topoisomerases.
      Finally, some trypanosomatids have life cycle stages exhibiting very different
      mitochondrial activities and can therefore serve as a model system for the
      regulation of mitochondrial biogenesis.

PMID- 11595227
TI  - Hitch-hiking parasite: a dark horse may be the real rider.
AB  - Many parasites engaged in complex life cycles manipulate their hosts in a way
      that facilitates transmission between hosts. Recently, a new category of
      parasites (hitch-hikers) has been identified that seem to exploit the
      manipulating effort of other parasites with similar life cycle by preferentially
      infecting hosts already manipulated. Thomas et al. (Evolution 51 (1997) 1316)
      showed that the digenean trematodes Microphallus papillorobustus (the
      manipulator) and Maritrema subdolum (the hitch-hiker) were positively associated
      in field samples of gammarid amphipods (the intermediate host), and that the
      behaviour of Maritrema subdolum rendered it more likely to infect manipulated
      amphipods than those uninfected by M. papillorobustus. Here I provide
      experimental evidence demonstrating that M. subdolum is unlikely to be a hitch
      hiker in the mentioned system, whereas the lucky candidate rather is the closely
      related but little known species, Microphallidae sp. no. 15 (Parassitologia 22
      (1980) 1). As opposed to the latter species, Maritrema subdolum does not express
      the appropriate cercarial behaviour for hitch-hiking.

PMID- 11595228
TI  - Patterns of parasite aggregation in the wild European rabbit (Oryctolagus
      cuniculus).
AB  - Understanding the factors controlling the distribution of parasites within their
      host population is fundamental to the wider understanding of parasite
      epidemiology and ecology. To explore changes in parasite aggregation, Taylor's
      power law was used to examine the distributions of five gut helminths of the wild
      rabbit. Aggregation was found to be a dynamic process that varied with year,
      season, host sex, age class, and myxomatosis. Yearly and seasonal changes are
      thought, in the main, to be the result of variations in weather conditions acting
      upon infectious stages (or intermediate hosts). Evidence in support of this was
      the comparatively low degree of fluctuation in the aggregation of the pinworm,
      Passalurus ambiguus, as the infectious stage of this parasite is likely to be
      less susceptible to environmental variation. Host age had a marked effect on the
      level of aggregation of all parasites, but this effect varied between parasite
      species. P. ambiguus, Trichostrongylus retortaeformis and Cittotaenia denticulata
      aggregation were lower in adult than juvenile rabbits whilst Graphidium strigosum
      and Mosgovoyia pectinata aggregation tended to increase with age. Host immunity
      is thought to be responsible for these differences. Differences in aggregation
      for different parasites were also seen when the rabbit population was split into
      males and females. Myxomatosis had a marked effect on helminth distribution with
      substantially less aggregation in rabbits showing clinical signs of the disease.

PMID- 11595229
TI  - Immunisation of cattle with cysteine proteinases of Trypanosoma congolense:
      targetting the disease rather than the parasite.
AB  - In order to test the hypothesis that trypanosome cysteine proteinases (CPs)
      contribute to pathology of trypanosomosis, cattle were immunised with CP1 and/or
      CP2, the major CPs of Trypanosoma congolense, and subsequently challenged with T.
      congolense. Immunisation had no effect on the establishment of infection and the
      development of acute anaemia. However, immunised cattle, unlike control cattle,
      maintained or gained weight during infection. Their haematocrit and leukocyte
      counts showed a tendency to recovery after 2-3 months of infection. Cattle
      immunised with CP2 mounted early and prominent IgG responses to CPs and to the
      variable surface glycoprotein following challenge. Thus trypanosome CPs may play
      a role in anaemia and immunosuppression; conversely, anti-CP antibody may
      modulate the trypanosome-induced pathology.

PMID- 11595230
TI  - Functional expression of the catalytic domains of two cysteine proteinases from
      Trypanosoma congolense.
AB  - The catalytic domains of two closely related cysteine proteinases (CP1 and CP2)
      from Trypanosoma congolense, referred to as C1 and C2, were expressed as proforms
      in Escherichia coli (C1) and in the baculovirus system (C1 and C2). While the
      bacterial expression system did not allow recovery of active C1, the baculovirus
      system led to secretion of inactive zymogens which could be processed at acidic
      pH into mature enzymes. Active C1 and C2 were purified from serum-free culture
      supernatants by anion-exchange chromatography and characterised. Their kinetic
      parameters and pH activity profiles confirmed the relatedness between C2 and
      native CP2 (congopain). These properties also underline major functional
      differences between C1 and C2, that appear to relate to discrete but essential
      sequence differences. It is likely that these two enzymes perform distinct roles
      in vivo, in the parasite and/or in the host-parasite relationships.

PMID- 11595231
TI  - Immunisation with Salmonella typhimurium-delivered glyceraldehyde-3-phosphate
      dehydrogenase protects mice against challenge infection with Echinococcus
      multilocularis eggs.
AB  - Recombinant glyceraldehyde-3-phosphate dehydrogenase of the cestode parasite
      Echinococcus multilocularis was expressed in Escherichia coli and in Salmonella
      typhimurium. The potential of different forms of the recombinant antigen to
      protect BALB/c mice against oral challenge infections with E. multilocularis eggs
      was evaluated. Oral or intraperitoneal immunisation with live attenuated S.
      typhimurium as a carrier for recombinant glyceraldehyde-3-phosphate dehydrogenase
      of the E. multilocularis resulted in significant protection, reducing the number
      of developing metacestodes up to 79.8%. The sera of protected animals did not
      contain detectable amounts of antibody against glyceraldehyde-3-phosphate
      dehydrogenase of E. multilocularis. By contrast, although anti-glyceraldehyde-3
      phosphate dehydrogenase of E. multilocularis antibodies were detectable in the
      sera, immunisation with E. coli-expressed recombinant glutathione-S-transferase
      fusion protein or with glyceraldehyde-3-phosphate dehydrogenase of E.
      multilocularis fused to a 6HIS-tag failed to protect the animals against oral
      challenge infections. These data emphasise that antigen delivery systems play a
      critical role in vaccination and the induction of protective immunity against
      helminth parasites.

PMID- 11595232
TI  - Inhibition of macrophage invasion by monoclonal antibodies specific to Leishmania
      (Viannia) braziliensis promastigotes and characterisation of their antigens.
AB  - Monoclonal antibodies that specifically recognise Leishmania (Viannia)
      braziliensis promastigotes were produced and termed SST-2, SST-3 and SST-4. SST-2
      recognises a conformational epitope present in a 24-28 kDa doublet and in a 72
      kDa component, as verified by Western blotting. Indirect immunofluorescence
      showed that the antigen recognised by SST-2 is distributed homogeneously on the
      parasite surface. SST-3 recognises a flagellar glycoprotein of approximately 180
      kDa. The reactivity of this mAb was abolished by sodium m-periodate treatment,
      indicating that SST-3 reacts with a carbohydrate epitope of the 180 kDa antigen.
      SST-4 recognises a conformational epitope of a 98 kDa antigen. SST-2, SST-3 and
      SST-4 were specific to L. (V.) braziliensis promastigote forms. Indirect
      immunofluorescence did not show reactivity of SST-2 or SST-3 with amastigotes of
      L. (V.) braziliensis, or with promastigotes of Leishmania (Viannia) panamensis,
      Leishmania (Viannia) guyanensis, Leishmania (Viannia) naiffi, Leishmania
      (Viannia) lainsoni, Leishmania (Leishmania) amazonensis, Leishmania (Leishmania)
      major, or Leishmania (Leishmania) chagasi. We also evaluated the involvement of
      SST-2, SST-3 and SST-4 antigens in parasite-macrophage interaction. Fab fragments
      of SST-3 and SST-4 significantly inhibited the infectivity of L. (V.)
      braziliensis promastigotes to mouse peritoneal macrophages.

PMID- 11595233
TI  - Immunisation of mice with fractions derived from the intestines of Dirofilaria
      immitis.
AB  - Antigens that are not normally seen by the host but that are nevertheless,
      accessible to host immune effector molecules and cells such as the native
      endoantigens associated with the intestinal epithelium of haematophagous tissue
      dwelling parasites, could be potentially useful vaccine antigens. In this study,
      intestines were dissected from adult Dirofilaria immitis, homogenised, and a
      105,000 x g pellet obtained and extracted with Triton X-100. The soluble 105,000
      x g supernatant from this extract induced partial protection (51%) against a
      challenge infection of third stage larvae (L3) implanted in micropore chambers.
      Sera from mice immunised with this soluble detergent extract reacted with
      proteins ranging in size from 38 to 130 kDa. Immunolocalisation studies indicated
      the mouse sera reacted primarily to the lumenal surface of the intestines of
      adult D. immitis, though reactivity to the lateral nerve/epithelial chords,
      hypodermis and reproductive tracts was also noted, indicating the presence of
      shared antigens. Tissues of L3s were also recognised by the immunised mouse sera.
      These mouse sera did not react to a dog blood fraction prepared identically to
      the D. immitis fraction. Only those sera from D. immitis-infected dogs with heavy
      or long-term infections were reactive to a single 42 kDa protein. After 24 h
      incubation in fluorescein isothiocyanate-conjugated serum the intestinal tract of
      Onchocerca volvulus and D. immitis L3 and L4 fluoresced, indicating the serum had
      been ingested. These data suggest that filarial gut-associated antigens (apart
      from the single 42 kDa antigen) are not seen by normally infected hosts, that
      they can be accessible to antibodies and that they can induce an immune response
      which is partially protective.

PMID- 11595234
TI  - Cytokines involved in the immunosuppressor period in experimental fasciolosis in
      rats.
AB  - The aim of this study was to evaluate the kinetics of the cytokines interferon
      gamma, interleukin-2, interleukin-10 and interleukin-4 produced by spleen
      mononuclear cells stimulated by Con A during an experimental infection in rats
      with Fasciola hepatica. The proliferative response to Con A of Spm cells from
      rats infected with F. hepatica was significantly decreased on day 7 post
      infection (P<0.006) and simultaneously an increase of interferon-gamma,
      interleukin-10 and interleukin-4 production along with a decrease of interleukin
      2 by spleen mononuclear cells were observed. Interleukin-4 and interleukin-10
      were involved in ablating cellular proliferation in vitro, as the addition of
      neutralising antibodies to either cytokine reversed the proliferative block. The
      addition of exogenous recombinant interleukin-2 also restored the proliferative
      response by spleen mononuclear cells obtained 7 days after infection from
      infected rats. At the same time, we found an increase in interleukin-10
      production by peritoneal cells (in close contact with the flukes) and decreased
      nitric oxide levels. In addition, histological studies on the liver on day 7
      after infection showed the presence of parasite inside migratory tunnels in the
      parenchyma, and polymorphonuclear leukocytes, predominantly eosinophils, around
      the parasite. The transient suppression in proliferative response mediated by
      cytokines interleukin-4 and interleukin-10 in the spleen, and diminution of
      nitric oxide production in the peritoneum could be mechanisms to evade the
      protective immune response during the first stages of liver penetration by the
      parasite.

PMID- 11595235
TI  - Sequence variability in the first internal transcribed spacer region within and
      among Cyclospora species is consistent with polyparasitism.
AB  - Cyclospora cayetanensis is a coccidian parasite which causes severe
      gastroenteritis in humans. Molecular information on this newly emerging pathogen
      is scarce. Our objectives were to assess genetic variation within and between
      human-associated C. cayetanensis and baboon-associated Cyclospora papionis by
      examining the internal transcribed spacer (ITS) region of the ribosomal RNA
      operon, and to develop an efficient polymerase chain reaction- (PCR)-based method
      to distinguish C. cayetanensis from other closely related organisms. For these
      purposes, we studied C. cayetanensis ITS-1 nucleotide variability in 24 human
      faecal samples from five geographic locations and C. papionis ITS-1 variability
      in four baboon faecal samples from Tanzania. In addition, a continuous sequence
      encompassing ITS-1, 5.8S rDNA and ITS-2 was determined from two C. cayetanensis
      samples. The results indicate that C. cayetanensis and C. papionis have distinct
      ITS-1 sequences, but identical 5.8S rDNA sequences. ITS-1 is highly variable
      within and between samples, but variability does not correlate with geographic
      origin of the samples. Despite this variability, conserved species-specific ITS-1
      sequences were identified and a single-round, C. cayetanensis-specific PCR-based
      assay with a sensitivity of one to ten oocysts was developed. This consistent and
      remarkable diversity among Cyclospora spp. ITS-1 sequences argues for
      polyparasitism and simultaneous transmission of multiple strains.

PMID- 11595236
TI  - Identification and characterisation of Toxoplasma gondii protein
      farnesyltransferase.
AB  - Prenylated proteins are involved in the regulation of DNA replication and cell
      cycling and have important roles in the regulation of cell proliferation. Protein
      farnesyltransferase and protein geranylgeranyltransferase are the two enzymes
      responsible for catalysing isoprene lipid modifications. Recently these enzymes
      have been targets for the development of cancer chemotherapeutics. Using
      metabolic labelling we identified isoprenylated proteins which suggests the
      presence of protein farnesyltransferase in Toxoplasma gondii. T. gondii protein
      farnesyltransferase is heat-labile and requires Mg(2+) and Zn(2+) ions for full
      activity. Peptidomimetic analogues as well as short synthetic peptides were
      tested in vitro as possible competitors for farnesyltransferase substrates. We
      found that the synthetic peptide (KTSCVIA) specifically inhibited T.
      gondiiprotein farnesyltransferase but not mammalian (HeLa cells)
      farnesyltransferase. Therefore this study suggests the possible development of
      specific inhibitors of T. gondiiprotein farnesyltransferase as an approach to
      parasitic protozoa therapy.

PMID- 11595237
TI  - Detection of malaria liver-stages in mice infected through the bite of a single
      Anopheles mosquito using a highly sensitive real-time PCR.
AB  - We describe a highly sensitive real-time PCR to detect and measure the
      development of the liver-stages of malaria parasites in mice infected with
      sporozoites ranging in number from 25 to more than 164,000, using the same
      reaction conditions. Furthermore, this assay detects and measures parasite loads
      in the livers of mice exposed to the bite of a single malaria-infected Anopheles
      mosquito. This unique method should greatly facilitate studies aimed at
      evaluating very precisely the efficacy of anti-malarial experimental drug
      treatments and vaccination regimens in conditions of infection resembling those
      found in the field.

PMID- 11595238
TI  - Vasoactive intestinal peptide and substance P-like immunoreactivities in the
      enteric nervous system of the pig correlate with the severity of pathological
      changes induced by Schistosoma japonicum.
AB  - Limited studies have shown that in intestinal schistosomosis, the enteric nervous
      tissue becomes inflamed, disrupted and destroyed by granulomas and peptides,
      amines and neurofilaments contents are altered. Therefore, immunoreactivities of
      vasoactive intestinal peptide and substance P were correlated to pathological
      lesions in the large intestine from pigs infected with Schistosoma japonicum.
      Ganglia situated within or near granulomas showed ganglionitis, and necrosis of
      neurons as well as infiltration by eosinophils, mast cells, lymphocytes, plasma
      cells, neutrophils and macrophages. The inner submucous and mucous plexuses were
      the most damaged. In all categories of inflamed areas, the vasoactive intestinal
      peptide-like immunoreactive was reduced in all plexuses whereas, that of
      substance P was increased both in the enteric nerve plexuses and enterochromaffin
      cells in lightly, moderately and severely inflamed tissues. However, both
      peptides were highly diminished or absent in very severe lesions and areas
      surrounding schistosome eggs and mature worms laying eggs in the submucosal
      veins. The alterations of the levels of vasoactive intestinal peptide and
      substance P were correlated with severity of inflammation. Our observations show
      alterations of vasoactive intestinal peptide and substance P contents in the
      local microenvironment in the vasoactive intestinal peptide- and substance P
      mediated reflex pathways which regulate intestinal motility, epithelial transport
      and modulate immunity. These changes could cause alterations in bowel motility,
      electrolyte and fluid secretion, vascular and immune functions during S.
      japonicum infections in the pig. This may, therefore, partly play a role in the
      pathobiology of migration and egress of schistosome eggs as well as influence
      trapping of eggs in granulomas, and account for diarrhoea, loss of body weight
      and failure to thrive, which are recorded in schistosomosis.

PMID- 11595239
TI  - Filaricidal efficacy of anthelmintically active cyclodepsipeptides.
AB  - PF 1022A, a novel anthelmintically active cyclodepsipeptide, and Bay 44-4400, a
      semisynthetic derivative of PF 1022A were tested for filaricidal efficacy in
      Mastomys coucha infected with Litomosoides sigmodontis, Acanthocheilonema viteae
      and Brugia malayi. The parent compound PF 1022A showed limited anti-filarial
      efficacy in L. sigmodontis and B. malayi infected animals. Oral doses of 5 x 100
      mg/kg on consecutive days caused only a temporary decrease of microfilariaemia
      levels. By contrast, Bay 44-4400 was highly effective against microfilariae of
      all three species in single oral, subcutaneous and cutaneously applied (spot on)
      doses. Minimum effective doses (MED, reducing parasitaemia density by > or =95%)
      determined 3 and 7 days after treatment were 3.125-6.25 and 6.25-12.5mg/kg,
      respectively. Using the spot on formulation, doses of 6.25mg/kg (L. sigmodontis),
      12.5mg/kg (A. viteae) and 25mg/kg (B. malayi) were required to cause reductions
      of microfilaraemia levels by > or =95% until day 56. Adulticidal effects,
      determined as minimum curative doses (MCD, eliminating adult parasites within 56
      days by >95%) after single dose treatment were limited to A. viteae (MCD,
      100mg/kg independent of the route of administration). Repeated oral treatment
      (100mg/kg on 5 consecutive days) killed all adult L. sigmodontis but did not
      affect B. malayi. However, single doses of 6.25 and 25mg/kg resulted in severe
      pathological alterations of intrauterine stages of L. sigmodontis and B. malayi,
      respectively. These alterations may be responsible for long-lasting reductions of
      microfilaraemia even when curative effects could not be achieved.

PMID- 11595240
TI  - Protection against vertical transmission in bovine neosporosis.
AB  - In this study we were interested to determine whether infection of cattle prior
      to pregnancy would afford any protection to the foetus if the dams were
      challenged with Neospora caninum at mid-gestation. The experiment comprised four
      groups of cattle: group 1, uninfected controls; group 2, inoculated with N.
      caninum tachyzoites 6 weeks prior to mating and then challenged with N. caninum
      at mid-gestation; group 3, naive cattle challenged with N. caninum at mid
      gestation and group 4 were infected with N. caninum prior to mating and left
      unchallenged throughout pregnancy. Positive cell-mediated and humoral immune
      responses to N. caninum were recorded in groups 2 and 4 prior to pregnancy and in
      groups 2, 3 and 4 following challenge at mid-gestation. However there was a
      marked down regulation of the cell-mediated immune response in all groups around
      mid-gestation. There was a significant increase in rectal temperature response in
      animals in group 3 compared to group 2 following challenge but no other clinical
      symptoms of disease were recorded and all cattle proceeded to calving. At
      calving, pre-colostral blood samples were negative for antibodies to N. caninum
      in all the calves born to dams in groups 1, 2 and 4. In contrast, all the calves
      born to dams in group 3 had high levels of specific antibody to N. caninum
      indicating that they had been exposed to the parasite in utero. At post-mortem N.
      caninum DNA was detected in CNS, thymus and placental cotyledon samples in calves
      from group 3. All tissue samples from calves in the other 3 groups were negative
      for N. caninum DNA with the exception of one calf from group 2 where specific DNA
      was detected in a sample of spinal cord. These results suggest that the immune
      response generated in the dams in group 2 prior to pregnancy had protected
      against vertical transmission of the parasite following challenge at mid
      gestation.

PMID- 11595242
TI  - How many functional somatic syndromes?
AB  - OBJECTIVE: Patients with medically unexplained symptoms are given diagnoses
      dependent upon the particular medical specialty consulted--irritable bowel
      syndrome in gastroenterology, fibromyalgia in rheumatology and others. The
      purpose of this paper is to establish whether these 13 different syndromes are
      discrete entities. METHODS: Consecutive new patients in seven outpatient clinics
      at two general hospitals were recruited. Patients completed questionnaires
      measuring symptoms and demographic data. Case notes were reviewed to ascertain
      whether the presenting symptoms were medically explained 3 months after the
      initial visit. RESULTS: Complete data were available for 550 subjects. With 37
      unexplained symptoms included in the model, 30% of the total variance could be
      explained by one factor using unrotated principal component analysis. When the 13
      identified functional syndromes were included, it was evident that functional
      syndromes could not be assumed to be independent. A two-factor model was the best
      fit for the present data after rotation. CONCLUSIONS: This study suggests that
      the existence of distinct functional somatic syndromes (FSSynd) as defined
      clinically in medicine should be reconsidered.

PMID- 11595241
TI  - Phylogenetic analysis of the Monocotylidae (Monogenea) inferred from 28S rDNA
      sequences.
AB  - The current classification of the Monocotylidae (Monogenea) is based on a
      phylogeny generated from morphological characters. The present study tests the
      morphological phylogenetic hypothesis using molecular methods. Sequences from
      domains C2 and D1 and the partial domains C1 and D2 from the 28S rDNA gene for 26
      species of monocotylids from six of the seven subfamilies were used. Trees were
      generated using maximum parsimony, neighbour joining and maximum likelihood
      algorithms. The maximum parsimony tree, with branches showing less than 70%
      bootstrap support collapsed, had a topology identical to that obtained using the
      maximum likelihood analysis. The neighbour joining tree, with branches showing
      less than 70% support collapsed, differed only in its placement of Heterocotyle
      capricornensis as the sister group to the Decacotylinae clade. The molecular tree
      largely supports the subfamilies established using morphological characters.
      Differences are primarily how the subfamilies are related to each other. The
      monophyly of the Calicotylinae and Merizocotylinae and their sister group
      relationship is supported by high bootstrap values in all three methods, but
      relationships within the Merizocotylinae are unclear. Merizocotyle is
      paraphyletic and our data suggest that Mycteronastes and Thaumatocotyle, which
      were synonymized with Merizocotyle after the morphological cladistic analysis,
      should perhaps be resurrected as valid genera. The monophyly of the Monocotylinae
      and Decacotylinae is also supported by high bootstrap values. The Decacotylinae,
      which was considered previously to be the sister group to the Calicotylinae plus
      Merizocotylinae, is grouped in an unresolved polychotomy with the Monocotylinae
      and members of the Heterocotylinae. According to our molecular data, the
      Heterocotylinae is paraphyletic. Molecular data support a sister group
      relationship between Troglocephalus rhinobatidis and Neoheterocotyle rhinobatidis
      to the exclusion of the other species of Neoheterocotyle and recognition of
      Troglocephalus renders Neoheterocotyle paraphyletic. We propose Troglocephalus
      incertae sedis. An updated classification and full species list of the
      Monocotylidae is provided.

PMID- 11595243
TI  - The significance of life-events as contributing factors in childhood recurrent
      abdominal pain in an urban community in Malaysia.
AB  - This study aimed to look at the link between childhood recurrent abdominal pain
      (RAP) and the presence of recent life-events in an urban community in Malaysia.
      School children aged from 9 to 15 years in the city of Petaling Jaya were
      randomly selected to fill in a questionnaire and to be interviewed. The
      prevalence of RAP among 1488 school children studied was 9.6% (95% confidence
      interval (CI), 8.18-11.25). Higher prevalences of RAP were found in children who
      had experienced the following life-events in the previous year: loss of a family
      member through death (P<.001), hospitalisation of a family member (P<.001), the
      child's own hospitalisation (P=.001), change of address (P<.001), change in
      occupation of an immediate family member (P<.001), failure in a major school
      examination (P<.001), bullying at school (P=.001). Following logistic regression
      analysis, five life-events remain significant: hospitalisation of a family member
      (P=.038), the child's own hospitalisation (P=.034), change in occupation of an
      immediate family member (P=.049), examination failure (P=.001) and bullying at
      school (P=.028). This study strongly suggests that recent stressful life-events
      are important risk-factors for RAP.

PMID- 11595244
TI  - Educational achievement and pain disability among women with chronic pelvic pain.
AB  - OBJECTIVE: This study examined the relationship of level of educational (LOE)
      achievement to pain experience, affective disturbance, and perceived disability
      among women with chronic pelvic pain presenting for pain treatment. METHODS: 187
      patients completed a battery of self-report inventories assessing pain,
      psychological status, and functional ability. Educational attainment was
      stratified across five levels from "less than high school" to
      "graduate/professional school." RESULTS: Significant inverse associations were
      found between lower educational achievement and more severe pain, somatic
      preoccupation, emotional suffering and guardedness, and functional impairment. No
      differences were obtained across the groups for age, duration of pain, or
      symptoms of depression. CONCLUSIONS: These data provide support for the
      importance of socioeconomic factors, particularly LOE, in furthering our
      understanding of the morbidity observed among women suffering chronic pelvic
      pain.

PMID- 11595245
TI  - Premorbid "overactive" lifestyle in chronic fatigue syndrome and fibromyalgia. An
      etiological factor or proof of good citizenship?
AB  - OBJECTIVE: In a former study, we have shown that patients suffering from chronic
      fatigue syndrome (CFS) or chronic pain, when questioned about their premorbid
      lifestyle, reported a high level of "action-proneness" as compared to control
      groups. The aim of the present study was to control for the patients' possible
      idealisation of their previous attitude towards action. METHODS: A validated
      Dutch self-report questionnaire measuring "action-proneness" (the HAB) was
      completed by 62 randomly selected tertiary care CFS and fibromyalgia (FM)
      patients, as well as by their significant others (SOs). RESULTS: HAB scores of
      the patients and those of the SOs were very similar and significantly higher than
      the norm values. Whether or not the SO showed sympathy for the patient's illness
      did not influence the results to a great extent. SOs with a negative attitude
      towards the illness even characterized the patients as more "action-prone."
      CONCLUSIONS: These results provide further support for the hypothesis that a high
      level of "action-proneness" may play a predisposing, initiating and/or
      perpetuating role in CFS and FM.

PMID- 11595246
TI  - Optimistic explanatory style and dispositional optimism in HIV-infected men.
AB  - OBJECTIVE: This study examined associations of two types of optimism (Peterson
      and Seligman's optimistic explanatory style and Scheier and Carver's
      dispositional optimism) with each other as well as with symptoms and immune
      status among human immunodeficiency virus (HIV)-infected men. METHOD: We related
      both types of optimism to HIV symptoms and to CD4 counts in a cross-sectional
      study of 78 men, and to change in CD4 counts in a 2-year prospective study of a
      subsample of these men. RESULTS: Analyses controlled for age, education,
      employment status, duration since diagnosis, and azidothymidine (AZT) use. The
      two types of optimism were only minimally related to each other (r=.25). Cross
      sectionally, higher levels of both types of optimism were associated with having
      fewer HIV symptoms, but a more optimistic explanatory style was related to having
      poorer immune status (lower CD4). Prospectively, an optimistic explanatory style
      was a substantial predictor of greater decline in CD4 counts after 2 years, after
      controlling for baseline CD4. Dispositional optimism was unrelated to CD4 counts.
      Neither health behaviors nor coping strategies mediated these relationships, and
      the relationships of optimistic explanatory style (and to a lesser extent,
      dispositional optimism) were independent of negative affectivity. CONCLUSIONS:
      These optimism measures tap different types of optimism, and although both are
      related to better subjective health in HIV-infected men, an optimistic
      explanatory style predicts greater decline in immune status over time. This
      latter relationship may be related to the unique stress and life experiences
      associated with having HIV.

PMID- 11595247
TI  - Anxiety and surgical recovery. Reinterpreting the literature.
AB  - OBJECTIVE: To critically evaluate the interpretation of the findings reported in
      the peer-reviewed literature concerning the association of state and trait
      anxiety with surgical recovery and response to surgery. METHODS: The Social
      Science Citation Index (SSCI), Science Citation Index (SCI), Medline and
      Psychological Abstracts (PsycInfo) databases were searched for studies published
      since 1981. Reference lists from previous reviews were also searched for
      additional references. Studies that were not in the public domain were not
      searched for. RESULTS: Twenty-seven studies were identified by the search
      strategy, met the inclusion criteria and contributed to the review. CONCLUSIONS:
      Associations between preoperative measures of anxiety and postoperative mood and
      pain have been consistently reported. Associations with regard to other recovery
      variables are less consistent. The existing evidence does not rule out an
      interpretation of the results as reflecting consistent self-reporting bias rather
      than causal association.

PMID- 11595248
TI  - Impact of Transcendental Meditation on cardiovascular function at rest and during
      acute stress in adolescents with high normal blood pressure.
AB  - OBJECTIVE: This study examined the impact of the Transcendental Meditation (TM)
      program on cardiovascular (CV) reactivity in adolescents with high normal BP.
      METHOD: Thirty-five adolescents [34 African Americans (AAs), 1 Caucasian American
      (CA); ages 15-18 years] with resting systolic blood pressure (SBP) between the
      85th and 95th percentile for their age and gender on three consecutive occasions,
      were randomly assigned to either TM (n=17) or health education control (CTL,
      n=18) groups. The TM group engaged in 15-min meditation twice each day for 2
      months including sessions during school lunch break. Primary CV outcome measures
      were changes in blood pressure (BP), heart rate (HR), and cardiac output (CO) at
      rest and in response to two laboratory stressors, a simulated car driving
      stressor and an interpersonal social stressor interview. RESULTS: The TM group
      exhibited greater decreases in resting SBP (P<.03) from pre- to postintervention,
      compared to the CTL group. The TM group exhibited greater decreases from pre- to
      postintervention in SBP, HR, and CO reactivity (P's<.03) to the simulated car
      driving stressor, and in SBP reactivity (P<.03) to the social stressor interview.
      CONCLUSION: The TM program appears to have a beneficial impact upon CV
      functioning at rest and during acute laboratory stress in adolescents at-risk for
      hypertension.

PMID- 11595249
TI  - Defensive coping styles in chronic fatigue syndrome.
AB  - OBJECTIVE: The cognitive-behavioral model of chronic fatigue syndrome (CFS)
      proposes that rigidly held beliefs act to defend individuals against low self
      esteem. This study is the first to investigate the prevalence of a potential
      mechanism, the Defensive High Anxious coping style, among individuals with CFS.
      METHODS: The study comprised 68 participants (24 CFS; 24 healthy volunteers; 20
      chronic illness volunteers). Participants completed the Bendig short form of the
      Taylor Manifest Anxiety Scale (B-MAS) and the Marlowe-Crowne Social Desirability
      Scale (MC) in order to ascertain the distribution of participants in each group
      within the four coping styles defined by Weinberger et al. [J. Abnorm. Psychol.
      88 (1979) 369]. RESULTS: A greater number of participants in the CFS group (46%)
      were classified as Defensive High Anxious compared to the two comparison groups
      [chi(2)(2)=8.84, P=.012]. CONCLUSION: This study provides support for the
      existence of defensive coping mechanisms as described by the cognitive-behavioral
      model of CFS. Furthermore, it has been suggested that this particular coping
      style may impinge directly on physical well being through similar mechanisms as
      identified in CFS, and further research linking these areas of research is
      warranted.

PMID- 11595250
TI  - Psychological factors associated with delay in attending hospital following a
      myocardial infarction.
AB  - OBJECTIVE: There is wide variability in latency to attend hospital following a
      myocardial infarction (MI). The present study assessed possible psychological
      factors that may be implicated in delayed presentation. METHOD: Seventy-two
      patients who had experienced a confirmed MI were interviewed in hospital, 3-5
      days post-MI. They completed a series of psychological measures of cardiac
      denial, cardiac threat, alexithymia, health locus of control, neuroticism and
      mood. RESULTS: Those patients who believed that they were having a heart attack
      sought help quicker than those who did not, and those who waited over 4 hours
      prior to seeking medical help had significantly lower scores on neuroticism, and
      higher scores on denial and health locus of control (chance). Confirmatory
      multiple regression analysis using an alternative estimate of delay in seeking
      help confirmed that health locus of control (chance) was the best predictor of
      delayed attendance. CONCLUSION: The present study confirms that the belief that
      one is having a MI is associated with prompt attendance, and additionally that
      the belief that health outcomes are largely due to chance factors is associated
      with delayed presentation following a MI. This delay could prove fatal.
      Modification of such beliefs may reduce response times and, thus, increase
      survival rates.

PMID- 11595254
TI  - Differential algebra methods for the study of the structural identifiability of
      rational function state-space models in the biosciences.
AB  - In this paper methods from differential algebra are used to study the structural
      identifiability of biological and pharmacokinetics models expressed in state
      space form and with a structure given by rational functions. The focus is on the
      examples presented and on the application of efficient, automatic methods to test
      for structural identifiability for various input-output experiments. Differential
      algebra methods are coupled with Grobner bases, Lie derivatives and the Taylor
      series expansion in order to obtain efficient algorithms. In particular, an upper
      bound on the number of derivatives needed for the Taylor series approach for a
      structural identifiability analysis of rational function models is given.

PMID- 11595255
TI  - Periodic coexistence in the chemostat with three species competing for three
      essential resources.
AB  - A chemostat model of three species of microorganisms competing for three
      essential, growth-limiting nutrients is considered. J. Husiman and F.J. Weissing
      [Nature 402 (1999) 407] show numerically that this model can generate periodic
      oscillations. The present contribution is concerned with rigorous analysis
      regarding the existence of periodic oscillations in this model. Our analysis is
      based on the following observation made by Huisman and Weissing: there is a
      cyclic replacement of species, if each species becomes limited by the resource
      for which it is the intermediate competitor. Using a permanence theory, an index
      theory, and a Poincare-Bendixson theory for three-dimensional competitive
      systems, we analytically succeed to give sufficient conditions for the existence
      of periodic orbits in the limit sets in this model. The results in this paper
      suggest that with a wide range of parameter values, sustained periodic
      oscillations of species abundances for the model are possible, without involving
      external disturbances. Our results also suggest that competition is not
      necessarily destructive, i.e., in the case of existence of sustained periodic
      oscillations, if one of three competitors is absent, one of the other two rivals
      cannot survive.

PMID- 11595256
TI  - Multi-stimulus multi-response posturography.
AB  - In this study a method for the analysis of simultaneous multiple measurements of
      kinematics and stabilizing forces related to human postural dynamics is proposed.
      Each subject in a group of normal subjects (n=10) was tested with eyes-open and
      eyes-closed with simultaneous but uncorrelated vestibular and proprioceptive
      stimuli in order to investigate the contributions of individual sensory feedback
      loops. Statistical analysis was made by means of multi-input multi-output
      identification of a transfer function from stimuli to stabilizing forces of the
      feet and the resulting body position, the transfer function being compatible with
      a biomechanical model formulated as a stabilized segmented inverted pendulum
      subject to feedback of body sway and position. Each individual model estimated is
      effective in predicting a subject's response to new stimuli and in describing the
      interacting effects of stimuli on body kinetics. The proposed methodology
      responds to the current needs of data analysis of multi-stimulus multi-response
      experiments.

PMID- 11595257
TI  - Coffee in the cornflakes: time-of-day as a modulator of executive response
      control.
AB  - Previous self-report based research has revealed a heightened propensity to slips
      of-action in the early morning and at the end of the day. Here, we examined
      performance variability among healthy young adults as a function of time-of-day
      on a clinical task that is sensitive to absent-minded slips in brain-injured
      groups. We found significantly higher error rates at 1 pm and 7 pm compared with
      1 am and 7 pm, and significant correlations between errors and two subjective
      sleepiness scales. No circadian modulation of the more routine aspects of the
      task was observed suggesting some specificity to the effect. Given evidence that
      the circadian cycle differentially affects different brain regions, and links
      between sleep deprivation and 'normal' dysexecutive behaviour, examining
      variation over the course of the day can prove a useful additional methodology in
      this area

PMID- 11595258
TI  - Sustained attention and inhibition of cognitive interference in treated
      phenylketonuria: associations with concurrent and lifetime phenylalanine
      concentrations.
AB  - Fifty-seven 7-14-year-old early- and continuously treated phenylketonuria (PKU)
      patients and 65 matched controls performed a sustained attention task. PKU
      patients with plasma phenylalanine (phe) levels higher than 360 micromol/l at the
      time of testing exhibited, compared to controls, lower speed of information
      processing, a lower ability to inhibit task-induced cognitive interference, less
      consistent performance, and a stronger decrease of performance level over time.
      Patients with concurrent phe levels lower than 360 micromol/l did not differ from
      controls and were significantly better than patients with levels higher than 360
      micromol/l. Strong relationships were found with task performance for phe levels
      during the pre-school years and between ages 5 and 7. These correlations were
      stronger than those between concurrent phe level and task performance.
      Significant multiple regression models were found with age accounting for the
      largest proportion of variance of tempo and tempo fluctuation, and lifetime phe
      levels (particularly phe level between ages 5 and 7) accounting for the largest
      proportion of variance of the relative number of inhibition errors and its
      increase over time. Phe level between ages 5 and 7 also contributed significantly
      to the variance of tempo and tempo fluctuation. Neuropsychological outcome was
      independent of IQ. The results indicate that strict dietary adherence during
      these periods is beneficial to attentional control later in life. We suggest that
      phe levels should be maintained under 360 micromol/l until approximately age 12,
      when development of attentional control approaches an adult level.

PMID- 11595259
TI  - Fast adjustments of ongoing movements in hemiparetic cerebral palsy.
AB  - The present study focuses on the ability of participants with spastic hemiparesis
      caused by cerebral palsy to adjust an ongoing movement. Typical symptoms
      associated with the disorder would lead one to expect that people with spastic
      hemiparesis would be unable to adjust their movements quickly and proportionally
      to a sudden change in the environment with their spastic arm. The results of the
      present experiment, however, prove otherwise. Eight hemiparetic adolescents with
      cerebral palsy and eight healthy control participants were asked to quickly hit a
      target projected onto a fronto-parallel screen. The target either remained
      stationary or started to move immediately after hand movement onset. Participants
      needed to adapt the ongoing movement to hit moving targets. The task was
      performed with the spastic and non-spastic arm by the hemiparetic participants
      and with the dominant arm by the healthy participants. Kinematic analyses showed
      that although the spastic arm of the hemiparetic participants displayed a
      significant increase in spatial variability which led to more errors, they were
      capable of successfully adapting their movement in a qualitative manner. The
      latency of the response to the change in target position was longer for the
      hemiparetic participants compared to the healthy control participants, but only
      25 ms. Surprisingly, no between arm latency difference was found in the
      hemiparetic participants. Given the commonly observed movement deficits of the
      spastic arm, these results show that participants with spastic hemiparesis
      displayed a remarkable ability in adjusting movements quickly.

PMID- 11595260
TI  - Focal retrograde amnesia documented with matching anterograde and retrograde
      procedures.
AB  - Focal retrograde amnesia is an unusual and theoretically challenging form of
      memory disorder. The case of a 65-year-old woman presenting with focal retrograde
      amnesia is reported. Following a cardiac arrest and subsequent hypoxia she
      remained in a coma for 24 h with evidence of epileptiform activity during the
      early recovery period. MR scans, 4 and 7 months post-onset, showed mild bifrontal
      atrophic changes mainly affecting white matter areas. An [18F]fluorodeoxyglucose
      resting PET scan 1-year post-onset demonstrated right occipito-temporo-parietal
      hypometabolism. We were able to document the patient's performance on an
      extensive range of anterograde and retrograde tests and to monitor her recovery
      of function by assessing her performance at 4, 12 and 24 months post-onset.
      Spared anterograde memory was observed on a range of verbal and non-verbal tests,
      including matched tasks that compared pre-illness and post-illness onset
      recollections. In contrast, her performance on retrograde memory tests, using
      detailed autobiographical and public events verbal and photographic tasks, showed
      a temporally-graded retrograde amnesia, more particularly affecting memory for
      autobiographical episodes. Possible mechanisms underlying CH's focal retrograde
      amnesia are discussed in terms of Damasio's time-locked multiregional
      retroactivation model.

PMID- 11595261
TI  - Cerebral hemodynamic response induced by the Tower of Hanoi puzzle and the
      Wisconsin Card Sorting test.
AB  - Transcranial Doppler sonography (TCD) was applied in normal subjects to
      investigate the effect of prefrontal functions like the Tower of Hanoi (TOH) task
      and the Wisconsin Card Sorting test (WCST) on cerebral hemodynamics. In 20
      healthy volunteers, left and right middle cerebral artery (MCA) and anterior
      cerebral artery (ACA) were insonated. The TOH task and the WCST were administered
      while cerebral blood flow velocity (CBFV) was registered. Each test was repeated
      once per artery pair. There was a visuomotor test to control the motor and visual
      stimulations. Three phases of CBFV time course were detected: an initial peak
      within 5 s, a following decrease within 25 s and a steady state beginning at 40
      s. The TOH task, WCST and visuomotor tests had different mean CBFV during the
      initial peak (MCA: P<0.05; ACA: P<0.05) as well as for the decrease (ACA: P<0.01)
      and the steady state (MCA: P<0.01; ACA: P<0.01). The TOH showed an increased mean
      CBFV as compared with the WCST during the steady state (MCA: P<0.01; ACA:
      P<0.05). However, temporal modulation of mean CBFV during category shift of the
      WCST resulted in significantly increased values after category shift (MCA:
      P<0.001; ACA: P<0.01) as compared with CBFV before the category shift. These
      findings showed a different CBFV pattern during the TOH task and WCST than during
      the visuomotor test. In conclusion, TCD was able to assess CBFV in prefrontal
      functions, using a high resolution in time.

PMID- 11595262
TI  - Is there an anatomical basis for category-specificity? Semantic memory studies in
      PET and fMRI.
AB  - Patients with semantic impairments sometimes demonstrate category-specific
      deficits suggesting that the anatomical substrates of semantic memory may reflect
      categorical organisation, however, neuroimaging studies have failed to provide
      consistent data in support of a category-based account. We conducted three
      functional neuroimaging experiments to investigate the neural correlates of
      semantic processing, two with positron emission tomography (PET) and a third with
      functional magnetic resonance imaging (fMRI). The first experiment used a lexical
      decision task to search for brain regions selectively activated by concepts from
      four different categories--animals, fruit, tools, and vehicles. The second
      experiment used a semantic categorisation task to increase the demands on the
      semantic system and to look for evidence of consistent activations for the
      domains of natural kinds or man-made items. The final experiment was a
      replication of the semantic categorisation task using fMRI to increase the
      spatial resolution and statistical sensitivity of the experiment. The results of
      these experiments reliably identified a distributed neural system common to both
      natural kinds and artifacts but failed to find robust evidence of functional
      segregation by domain or categories. Category effects were neither reliable nor
      consistently present across experiments although some were consistent with
      previous studies. We discuss the implications of these findings, arguing that
      they are most consistent with a semantic system undifferentiated by category at
      the neural level.

PMID- 11595263
TI  - Inhibition of ongoing responses in patients with traumatic brain injury.
AB  - In addition to slowness of information processing, it is often assumed that
      executive functions are deficient in patients with traumatic brain injuries
      (TBI). The aim of this study was to investigate a specific executive function,
      the inhibition of ongoing responses in TBI. Twenty-seven patients with TBI and 27
      orthopedic patients (OC) performed the stop signal task, which allows the
      estimation of the time it takes to inhibit an ongoing response. Contrary to
      expectations, patients with TBI did not perform worse than the OC in the
      inhibition of ongoing responses. Furthermore, subgroups of the TBI, with frontal
      and nonfrontal lesions, and with focal versus diffuse damage, did not show any
      differences in performance. None of the clinical, demographic or
      neuropsychological data had a significant relationship to inhibition time, apart
      from age, which showed a significant relationship only in the TBI. It seems
      likely that deficits in the inhibition of ongoing responses are not very common
      after TBI.

PMID- 11595264
TI  - The effect of encoding strategy on the neural correlates of memory for faces.
AB  - Encoding and recognition of unfamiliar faces in young adults were examined using
      positron emission tomography to determine whether different encoding strategies
      would lead to encoding/retrieval differences in brain activity. Three types of
      encoding were compared: a 'deep' task (judging pleasantness/unpleasantness), a
      'shallow' task (judging right/left orientation), and an intentional learning task
      in which subjects were instructed to learn the faces for a subsequent memory test
      but were not provided with a specific strategy. Memory for all faces was tested
      with an old/new recognition test. A modest behavioral effect was obtained, with
      deeply-encoded faces being recognized more accurately than shallowly-encoded or
      intentionally-learned faces. Regardless of encoding strategy, encoding activated
      a primarily ventral system including bilateral temporal and fusiform regions and
      left prefrontal cortices, whereas recognition activated a primarily dorsal set of
      regions including right prefrontal and parietal areas. Within encoding, the type
      of strategy produced different brain activity patterns, with deep encoding being
      characterized by left amygdala and left anterior cingulate activation. There was
      no effect of encoding strategy on brain activity during the recognition
      conditions. Posterior fusiform gyrus activation was related to better recognition
      accuracy in those conditions encouraging perceptual strategies, whereas activity
      in left frontal and temporal areas correlated with better performance during the
      'deep' condition. Results highlight three important aspects of face memory: (1)
      the effect of encoding strategy was seen only at encoding and not at recognition;
      (2) left inferior prefrontal cortex was engaged during encoding of faces
      regardless of strategy; and (3) differential activity in fusiform gyrus was
      found, suggesting that activity in this area is not only a result of automatic
      face processing but is modulated by controlled processes.

PMID- 11595265
TI  - Event-related potentials recorded from the cingulate gyrus during attentional
      tasks: a study in patients with implanted electrodes.
AB  - Recent neuroimaging data suggests that the cingulate gyrus is involved in a
      variety of cognitive tasks. In this study sensory field potentials were directly
      recorded from the cingulate gyrus in order to investigate its implication in
      attentional processes associated or not with a motor task. Evoked potentials
      recordings were performed in 29 epileptic patients with multilead electrodes
      implanted for presurgical evaluation, who agreed to participate in an
      experimental protocol consisting of a series of paradigms designed using a
      warning auditory tone, two distinct visual patterns and various attentional,
      memory, motor and decisional tasks. Our data shows that evoked potentials could
      be recorded from various parts of the cingulate gyrus. The inclusion of an
      instruction in the experimental paradigm resulted in an increase in the amplitude
      of the late, intrinsic component of the visual evoked potential culminating at
      about 450 ms. Several variations of response patterns across individuals were
      identified. We conclude that the cingulate gyrus appears to be a multimodal area
      involved in several types of cognitive activity, including attention. Variations
      in response patterns are probably related to differences in the strategy adopted
      by each subject when faced with a particular cognitive task.

PMID- 11595266
TI  - Fractionation of visual memory: agency detection and its impairment in autism.
AB  - It is known that the adult visual memory system is fractionable into functionally
      independent cognitive subsystems, selectively susceptible to brain damage. In
      addition, there have been hints from studies with individuals with autism that
      these cognitive subsystems can fractionate developmentally. However, there has
      been a paucity of systematic investigations. The present study involves the
      analysis of visual memory of a population of individuals with autism and age- and
      VIQ-matched comparison individuals. The individuals with autism presented
      selective impairments in face recognition in comparison to both the age- and VIQ
      matched comparison populations. In addition, they were impaired relative to the
      age-matched comparison group on recognition memory for potential agents (i.e.
      objects capable of self-propelled motion) whether they were living (cats and
      horses) or non-living (motorbikes). In contrast, they were selectively superior
      relative to the VIQ-matched comparison group on recognition memory for such
      objects as topographical stimuli (buildings) and leaves that clearly do not have
      agency. The data is interpreted in terms of reduced sensitivity to agency cues in
      individuals with autism and general information processing capacity.

PMID- 11595267
TI  - Cognitive neuroscience: perception, attention, and memory.

PMID- 11595268
TI  - Mechanisms of human attention: event-related potentials and oscillations.
AB  - Electrophysiological and hemodynamical responses of the brain allow investigation
      of the neural origins of human attention. We review attention-related brain
      responses from auditory and visual tasks employing oddball and novelty paradigms.
      Dipole localization and intracranial recordings as well as functional magnetic
      resonance imaging reveal multiple areas involved in generating and modulating
      attentional brain responses. In addition, the influence of brain lesions of
      circumscribed areas of the human cortex onto attentional mechanisms are reviewed.
      While it is obvious that damaged brain tissue no longer functions properly, it
      has also been shown that functions of non-lesioned brain areas are impaired due
      to loss of modulatory influence of the lesioned area. Both early (P1 and N1) and
      late (P3) event-related potentials are modulated by excitatatory and inhibitory
      mechanisms. Oscillatory EEG-correlates of attention in the alpha and gamma
      frequency range also show attentional modulation.

PMID- 11595269
TI  - The attentive homunculus: now you see it, now you don't.
AB  - The nature of the neural system that directs our attention toward selective items
      in the extrapersonal world is a longstanding and interesting puzzle. The ability
      to image the human brain at work non-invasively using positron-emission
      tomography or functional magnetic resonance has provided the means to investigate
      this issue. In this article, I review the contributions of brain imaging toward
      the characterization of attentional control in the human brain. The majority of
      experiments to date have investigated visual spatial orienting. A consistent
      pattern of brain areas has been revealed, comprising most notably the posterior
      parietal cortex around the intraparietal sulcus and frontal regions including the
      frontal eye fields. The brain areas implicated in the control of visual spatial
      attention were noted to resemble those involved in the control of eye movements,
      and direct experimental comparisons supported a tight link between the two
      systems. The findings suggested a sensible view of the attentional 'homunculus'
      as a distributed neural system related to the control of eye movements. Eye
      movements form perhaps the most basic orienting response, and can be shifted
      rapidly and efficiently based on multiple frames of reference. Some attention
      experiments using objects and features instead of spatial locations as the target
      of selection also obtained similar patterns of parietal-frontal activations,
      rendering further support to this view of the attentional control system. Some
      recent experiments, however, have cautioned against a premature conclusion
      regarding the ubiquity of the attentional control system revealed by studies of
      visual spatial attention. Different parietal and frontal regions become engaged
      when attention is shifted along non-spatial dimensions, such as when attention is
      directed toward a particular motor act or toward a specific point in time. In
      these cases, the neural system resembles those involved in the control of limb
      movements. The attentional homunculus thus begins to dissolve. The alternative
      view suggested is that attentional control may be a property of specialized
      parietal-frontal systems that transform perception into action. Future studies
      will be needed to validate this view of attention, or to provide a more mature
      understanding of its true nature.

PMID- 11595270
TI  - Crossmodal links in endogenous and exogenous spatial attention: evidence from
      event-related brain potential studies.
AB  - The adaptive control of behaviour in response to relevant external objects and
      events often requires the selection of information delivered by different sensory
      systems, but from the same region in external space. This can be facilitated by
      crossmodal links in the attentional processing of information across sensory
      modalities. Results from recent event-related potential (ERP) studies are
      reviewed that investigated mechanisms underlying such crossmodal links in spatial
      attention between vision, audition and touch. Crossmodal attention effects were
      observed for early modality-specific visual, auditory, and somatosensory ERP
      components, indicating that crossmodal links in spatial attention affect sensory
      perceptual processes within modality-specific cortical regions. ERP modulations
      prior to target events but sensitive to the direction of an attentional shift
      were remarkably similar during anticipatory covert shifts of visual, auditory, or
      tactile attention. These results suggest that such attentional shifts are
      mediated by supramodal frontoparietal control mechanisms. Finally, ERP evidence
      is reviewed suggesting that effects of crossmodal links in endogenous (voluntary)
      as well as exogenous (involuntary) spatial attention are mediated by a
      representations of external space which are updated across postural changes.

PMID- 11595271
TI  - Linking the laminar circuits of visual cortex to visual perception: development,
      grouping, and attention.
AB  - How do the laminar circuits of visual cortical areas V1 and V2 implement context
      sensitive binding processes such as perceptual grouping and attention, and how do
      these circuits develop and learn in a stable way? Recent neural models clarify
      how preattentive and attentive perceptual mechanisms are intimately linked within
      the laminar circuits of visual cortex, notably how bottom-up, top-down, and
      horizontal cortical connections interact within the cortical layers. These
      laminar circuits allow the responses of visual cortical neurons to be influenced,
      not only by the stimuli within their classical receptive fields, but also by
      stimuli in the extra-classical surround. Such context-sensitive visual processing
      can greatly enhance the analysis of visual scenes, especially those containing
      targets that are low contrast, partially occluded, or crowded by distractors.
      Attentional enhancement can selectively propagate along groupings of both real
      and illusory contours, thereby showing how attention can selectively enhance
      object representations. Recent models explain how attention may have a stronger
      facilitatory effect on low contrast than on high contrast stimuli, and how pop
      out from orientation contrast may occur. The specific functional roles which the
      model proposes for the cortical layers allow several testable neurophysiological
      predictions to be made. Model mechanisms clarify how intracortical and
      intercortical feedback help to stabilize cortical development and learning.
      Although feedback plays a key role, fast feedforward processing is possible in
      response to unambiguous information. Model circuits are capable of synchronizing
      quickly, but context-sensitive persistence of previous events can influence how
      synchrony develops.

PMID- 11595272
TI  - Functional correlates of macroscopic high-frequency brain activity in the human
      visual system.
AB  - The present article reviews empirical findings of large-scale gamma oscillations
      in the human brain, in the context of their functional correlates. Evidence
      supporting the fact that high-frequency neuronal oscillations are involved in
      several aspects of visual processing is presented, with a focus on bottom-up and
      top-down visual feature processing, selective attention, and emotional
      evaluation. This evidence suggests that visual processing involves the integrated
      activity of wide spread neuronal assemblies that can be studied with respect to
      time course and topography, employing frequency-domain analyses. Possible
      mechanisms underlying these phenomena are considered. Furthermore, the effects of
      attention and motivation, as well as characteristics of experimental paradigms
      are discussed as determinants of reliability and validity of measures of high
      frequency oscillations.

PMID- 11595273
TI  - The mismatch negativity in evaluating central auditory dysfunction in dyslexia.
AB  - The mismatch negativity (MMN), a brain response elicited by a discriminable
      change in any repetitive aspect of auditory stimulation even in the absence of
      attention, has been widely used in both basic and clinical research during recent
      years. The fact that the MMN reflects the accuracy of auditory discrimination and
      that it can be obtained even from unattentive subjects makes it an especially
      attractive tool for studying various central auditory-system dysfunctions both in
      adults and children. In this review, we will discuss the applicability of the MMN
      to studies in dyslexia, which is currently thought, in the majority of the cases,
      to primarily result either from a dysfunction of the phonological system or a
      more general auditory deficit. Recent evidence indicates that the MMN enables one
      to determine which aspects of auditory information are deficiently processed in
      dyslexia. The MMN might also be helpful in the early definition of the dyslexia
      type, which would make it possible to start correctly-targeted training
      programmes before any major learning delays occur. Furthermore, the MMN holds
      promise of showing plastic changes in the brain of dyslexic individuals
      underlying the alleviation or remediation of dyslexia in the course of a
      successful training programme.

PMID- 11595274
TI  - Event-related functional imaging and episodic memory.
AB  - Electrical and haemodynamic measures of neural activity can be time-locked to an
      event-of-interest, such as the presentation of a stimulus or a behavioural
      response. Both of these measures can be employed in studies where the aim is to
      elucidate the relationship between neural activity and cognitive processes. This
      review highlights a number of considerations that arise when these techniques are
      employed in pursuit of this goal, with a particular emphasis on functional
      imaging studies of retrieval from episodic memory. The review includes: a
      discussion of some limitations that each technique imposes at the stage of
      experimental design, consideration of the relative strengths and weaknesses of
      each technique, a commentary on assumptions that are common to both, and a brief
      review of the ways in which these techniques can be extended in order to index
      two distinct classes of cognitive operations that have correspondingly distinct
      neural signatures.

PMID- 11595275
TI  - Exploring the neural bases of episodic and semantic memory: the role of
      structural and functional neuroimaging.
AB  - Exploration of the neural bases of episodic and semantic memory is best pursued
      through the combined examination of the effects of identified lesions on memory
      and functional neuroimaging of both normal people and patients when they engage
      in memory processing of various kinds. Both structural and functional
      neuroimaging acquisition and analysis techniques have developed rapidly and will
      continue to do so. This review briefly outlines the history of neuroimaging as it
      impacts on memory research. Next, what has been learned so far from lesion-based
      research is outlined with emphasis on areas of disagreement as well as agreement.
      What has been learned from functional neuroimaging, particularly emission
      tomography and functional magnetic resonance imaging, is then discussed, and some
      stress is placed on topics where the interpretation of imaging studies has so far
      been unclear. Finally, how functional and structural imaging techniques can be
      optimally used to help resolve three areas of disagreement in the lesion
      literature will be discussed. These disagreements concern what the hippocampus
      and perirhinal cortex contribute to memory; whether any form of priming depends
      on the medial temporal lobes; and whether remote episodic as well as semantic
      memories cease to depend on the medial temporal lobes. Although the discussion
      will show the value of imaging techniques, it will also emphasize some of the
      limitations of current neuroimaging studies.

PMID- 11595276
TI  - Comparison of Hilbert transform and wavelet methods for the analysis of neuronal
      synchrony.
AB  - The quantification of phase synchrony between neuronal signals is of crucial
      importance for the study of large-scale interactions in the brain. Two methods
      have been used to date in neuroscience, based on two distinct approaches which
      permit a direct estimation of the instantaneous phase of a signal [Phys. Rev.
      Lett. 81 (1998) 3291; Human Brain Mapping 8 (1999) 194]. The phase is either
      estimated by using the analytic concept of Hilbert transform or, alternatively,
      by convolution with a complex wavelet. In both methods the stability of the
      instantaneous phase over a window of time requires quantification by means of
      various statistical dependence parameters (standard deviation, Shannon entropy or
      mutual information). The purpose of this paper is to conduct a direct comparison
      between these two methods on three signal sets: (1) neural models; (2)
      intracranial signals from epileptic patients; and (3) scalp EEG recordings.
      Levels of synchrony that can be considered as reliable are estimated by using the
      technique of surrogate data. Our results demonstrate that the differences between
      the methods are minor, and we conclude that they are fundamentally equivalent for
      the study of neuroelectrical signals. This offers a common language and framework
      that can be used for future research in the area of synchronization.

PMID- 11595277
TI  - Trial to trial variability in either stimulus or action causes apparent
      correlation and synchrony in neuronal activity.
AB  - In this report we show that the observed inter-neuronal correlation reflects a
      superposition of correlations associated with the intrinsic correlation between
      neurons, and correlations associated with variability in the stimuli presented
      to, or the actions performed by, the subject. We argue that the effects of either
      stimulus or action variability on the observed correlation, though generally
      ignored, can be substantial. Specifically, we demonstrate how observed
      correlations are effected by trial to trial variability in either stimulus or
      action. In addition, assuming that all relevant stimuli and actions are known, we
      outline a method for eliminating their effects on the observed correlation. It is
      also shown that tuning of correlations to a stimulus or an action might be a
      direct consequence of variability in that stimulus or action, even in the absence
      of any modulation of direct inter-neuronal interaction. The effects of stimulus
      and action variability should therefore be carefully considered when designing
      and interpreting experiments involving multi-neuronal recordings.

PMID- 11595278
TI  - Estimation of the activation and kinetic properties of I(Na) and I(K) from the
      time course of the action potential.
AB  - A detailed knowledge of the quantitative properties of the currents I(Na) and
      I(K) underlying the action potential is essential for a deeper understanding of
      neuronal excitatory processes. However, it is not always possible or practical to
      perform voltage-clamp measurements that usually provide the necessary data. In
      this paper, we present a method by which the activation and kinetic properties of
      these currents can be estimated from current-clamp data, more precisely from the
      time course of the action potential, provided some additional
      electrophysiological properties of the neurone are a priori known. We report
      results from thalamocortical neurones and a cortical pyramidal cell, and suggest
      that the method will work with other types of neurones, if their action
      potentials are primarily shaped by I(Na) and I(K).

PMID- 11595279
TI  - Delay estimation for cortico-peripheral relations.
AB  - In neurophysiology, time delays between concurrently measured time series are
      usually estimated from the slope of a straight line fitted to the phase spectrum.
      We point out that this estimate is valid only in the case in which, one signal is
      a mere time-delayed copy of the other one. We present a procedure for delay
      estimation that applies to a much wider class of systems with nontrivial phase
      spectrum like for example lowpass filters. The procedure is based on the Hilbert
      transform relation between the phase of a linear system and its log gain. The
      Hilbert transform relation is nonlocal in frequency space, a fact that limits its
      applicability to experimental data. We explore these limits, and demonstrate that
      the method is applicable to neurophysiological time series. We present the
      successful application of the Hilbert transform behavior method to concurrently
      recorded epicortical brain activity and peripheral tremor. We point out and
      explain physiologically unreasonable delay estimates given by the traditional
      method. Finally, we discuss the assumptions underlying the applicability of the
      Hilbert transform method in the neuroscience context.

PMID- 11595280
TI  - Efficient evaluation of serial sections by iterative Gabor matching.
AB  - Evaluation of electron microscopic images of serial sections is a time-consuming
      process requiring a high level of expertise. Here we present an algorithm to ease
      and accelerate this process. It is a modification of an algorithm successfully
      used in computer vision for object recognition. However, rather than recognising
      individual structures, we estimate the spatial mapping of a whole section onto
      the consecutive one. This mapping is used to transfer labelled information of the
      very first section, e.g. a classification by a human expert of different visible
      structures, onto structures visible in the next section. We investigate its
      performance on an artificially constructed benchmark as well as on real electron
      microscopic samples taken in primary visual cortex and demonstrate its potential
      for dramatically facilitating the evaluation process of serial sections.

PMID- 11595281
TI  - PEGylated polycyanoacrylate nanoparticles as vector for drug delivery in prion
      diseases.
AB  - PEGylated polymeric nanoparticles are hereby presented as a potential efficient
      drug carrier for the delivery of active therapeutic molecules in prion
      experimental diseases. Based on their blood long-circulating characteristics,
      these PEGylated particles made by the amphiphilic copolymer poly [methoxy
      poly(ethylene glycol) cyanoacrylate-co-hexadecyl cyanoacrylate] (PEG-PHDCA),
      showed comparatively conventional non-PEGylated nanoparticles, a higher uptake by
      the spleen and the brain which are both the target tissues of PrPres accumulation
      in scrapie infected animals.

PMID- 11595282
TI  - FDOPA metabolism in the adult porcine brain: influence of tracer circulation time
      and VOI selection on estimates of striatal DOPA decarboxylation.
AB  - Different methodologies for PET data analysis influence the magnitude of
      estimates of blood-brain transfer coefficients and rate constants for the
      metabolism of FDOPA in living striatum. We now test the effects on several
      kinetic parameters of automatic procedures for volume of interest (VOI)
      selection. We also tested the sensitivity of the estimates to dynamic frame
      sequence duration, and produced a standard method for minimizing the variations
      in physiological estimates for FDOPA kinetics in minipig brain. We used minipigs
      because our previous work has shown them to provide an appropriate animal model
      for study normal and pathological cerebral DOPA metabolism using PET. Time
      activity curves in striatum of adult minipigs were acquired in VOIs defined
      manually on MR-images, or alternatively on the basis of the radioactivity
      concentration based on the most radioactive voxel in the last scan frame. For all
      frame sequences, the relative decarboxylase activity (k(3)(D)) declined
      significantly (P < 0.006) as the VOI threshold declined from 95 to 70% of the
      most radioactive voxel. Irrespective of VOI size, the magnitude of k(3)(D)
      declined significantly (P < 0.001) from 0.074+/-0.008 to 0.045+/-0.005 per min
      (mean+/-S.E.M.) as total sequence length increased from 60 to 120 min
      circulation. The method of VOI selection had no significant effect on the
      striatum decarboxylation index of FDOPA calculated relative to the radioactivity
      in cerebellum (k(3)(S)).

PMID- 11595284
TI  - New insights into HIV-1 specific cytotoxic T-lymphocyte responses in exposed,
      persistently seronegative Kenyan sex workers.
AB  - A clearer understanding of HIV-1 specific immune responses in highly-exposed,
      persistently seronegative (HEPS) subjects is important in developing models of
      HIV-1 protective immunity. HIV-1 specific cytotoxic T-lymphocytes (CTL) have been
      described in a cohort of HEPS Kenyan sex workers, and recent work has further
      elucidated these responses. CTL specific for HIV-1 Env were found in the blood of
      over half the sex workers meeting criteria for HIV resistance, and in some women
      recognized unmapped epitopes. The proportion of women with Env-specific CTL
      increased with the duration of uninfected HIV exposure, suggesting that these
      responses were acquired over time. CD8+ lymphocyte responses directed against
      predefined HIV-1 CTL epitopes from various HIV-1 genes were found in the blood
      and genital tract of >50% resistant sex workers, at a ten-fold lower frequency
      than in infected subjects. The epitope specificity of CD8+ responses differs
      between HEPS and HIV infected women, and in HEPS the maintenance of responses
      appears to be dependent on persistent HIV exposure. Several HIV-1 'resistant' sex
      workers have become HIV infected over the past 6 years, possibly related to
      waning of pre-existing HIV-specific CTL, and infection has often been associated
      with a switch in the epitope specificity of CD8+ responses. These findings
      suggest that vaccine-induced protective HIV immunity is a realistic goal, but
      that vaccine strategies of boosting or persistent antigen may be necessary for
      long-lived protection.

PMID- 11595285
TI  - How important is the 'quality' of the cytotoxic T lymphocyte (CTL) response in
      protection against HIV infection?
AB  - Cytotoxic T lymphocyte (CTL) responses have been associated with protection from
      HIV-1 infection in people with a high degree of exposure to HIV and who show no
      serological evidence of HIV infection (HEPS, highly exposed persistently
      seronegative). However, it remains unclear how protective CTL responses could
      apparently develop in a minority of people, whilst the great majority of HIV
      infected people make strong CTL responses yet progress to AIDS and death. In this
      paper we review the data which supports the hypothesis that the quality of the T
      cell response, rather than its magnitude, may be an important factor that merits
      further investigation.

PMID- 11595286
TI  - Immune defence against HIV-1 infection in HIV-1-exposed seronegative persons.
AB  - Rare individuals who are repeatedly exposed to HIV-1 through unprotected sexual
      contact fail to acquire HIV-1 infection. These persons represent a unique study
      population to evaluate mechanisms by which HIV-1 replication is either prevented
      or controlled. We followed longitudinally a group of healthy HIV-1 seronegative
      persons each reporting repeated high-risk sexual activities with their HIV-1
      infected partner at enrollment. The volunteers were primarily (90%) male
      homosexuals, maintaining high risk activities with their known infected partner
      (45%) or multiple other partners (61%). We evaluated the quantity and specificity
      of HIV-1-specific T cells in 31 exposed seronegatives (ES) using a IFN-gamma
      ELISPOT assay to enumerate T cells recognizing epitopes within HIV-1 Env, Gag,
      Pol and Nef. PBMC from only three of the 31 volunteers demonstrated ex vivo HIV-1
      specific IFN-gamma secretion, in contrast to nearly 30% exhibiting cytolytic
      responses in previous studies. These findings suggest that if T cell responses in
      ES are induced by HIV-1 exposure, the frequency is at low levels in most of them,
      and below the level of detection using the ELISPOT assay. Alternative approaches
      to improve the sensitivity of detection may include use of dendritic cells as
      antigen-presenting cells in the ex vivo assay and more careful definition of the
      risk behavior and extent of HIV-1 exposure in conjunction with the evaluation of
      T cell responses.

PMID- 11595287
TI  - Functional HIV-1 specific IgA antibodies in HIV-1 exposed, persistently IgG
      seronegative female sex workers.
AB  - Although HIV-specific cellular immune responses are found in a number of HIV
      highly-exposed, persistently seronegative (HEPS) cohorts, late seroconversion can
      occur despite pre-existing cytotoxic T lymphocytes (CTL), suggesting that a
      protective HIV vaccine may need to induce a broader range of HIV-specific immune
      responses. Low levels of HIV-specific IgA have been found in the genital tract
      and plasma of the majority of Nairobi HEPS sex workers and appeared to be
      independent of HIV-specific cellular responses. IgA purified from genital tract,
      saliva and plasma of most HEPS sex workers were able to neutralize infection of
      PBMC by a primary (NSI) clade B HIV isolate, as well as viral isolates from
      clades A and D, which predominate in Kenya. In addition, these IgA were able to
      inhibit transcytosis of infective HIV virions across a transwell model of the
      human mucosal epithelium in an HIV-specific manner. Preliminary work in other
      HEPS cohorts has suggested the recognition of different gp41 epitopes in HEPS and
      HIV-infected subjects. Although present at low levels, these IgA demonstrated
      cross-clade neutralizing activity and were able to inhibit HIV mucosal
      transcytosis, suggesting an important functional role in protection against HIV
      infection.

PMID- 11595288
TI  - CD8 CTL responses in vaccines: emerging patterns of HLA restriction and epitope
      recognition.
AB  - We evaluated MHC-class I-restricted CTL responses induced by HIV-1 clade B-based
      vaccines in nine HIV-1 seronegative vaccine recipients with regard to their
      patterns of HLA restriction and epitope recognition. We found that seven of nine
      volunteers developed detectable CTL reactivities against novel epitopes within
      the HIV-1 Env and Gag proteins. Although four of nine subjects were HLA-A*0201,
      none of the cellular responses was restricted in the context of this allele. The
      type of responses observed in this sampling of vaccines appeared similar to those
      reported during primary infection and among long term non-progressors, with three
      out of nine subjects recognizing HLA-B27 or HLA-B17(57)-restricted epitopes.
      Although the majority of CTL responses were directed against novel epitopes,
      these effectors were still able to mediate cross-clade reactivities.

PMID- 11595289
TI  - DNA-immunization with a V2 deleted HIV-1 envelope elicits protective antibodies
      in macaques.
AB  - Rhesus macaques immunized with the HIV-1 SF162DeltaV2 gp140 envelope using the
      DNA-prime plus protein-boost vaccination methodology, developed HIV envelope
      specific T-cell lymphoproliferative responses and potent neutralizing antibodies.
      To evaluate the protective potential of these antibodies during acute infection,
      the animals were depleted of their CD8+ T lymphocytes using specific monoclonal
      antibodies and subsequently challenged intravenously with the pathogenic
      SHIV(SF162P4) isolate. As compared to non-vaccinated animals (one of which died
      from AIDS 16 weeks post-exposure) the vaccinated macaques had lower levels of
      peak viremia, rapidly cleared virus from the periphery and developed delayed
      seroconversion to SIV core antigens.

PMID- 11595290
TI  - Vaccine-elicited immune responses prevent clinical AIDS in SHIV(89.6P)-infected
      rhesus monkeys.
AB  - Accumulating evidence has demonstrated the importance of cytotoxic T lymphocytes
      (CTLs) and helper T lymphocytes in controlling HIV-1 replication. We have
      elicited immune responses in rhesus monkeys utilizing DNA vaccines augmented by
      the administration of IL-2/Ig, a fusion protein consisting of interleukin-2 and
      the Fc portion of IgG2. These vaccine-elicited immune responses did not prevent
      infection following a high-dose intravenous challenge with SHIV(89.6P) but did
      control viremia to nearly undetectable levels and prevented immunodeficiency and
      clinical disease. In contrast, control monkeys developed high levels of viremia
      and exhibited a rapid loss of CD4(+) T cells, significant clinical disease
      progression, and death in half of the animals by day 140 following challenge.
      Vaccine approaches that elicit immune responses capable of reducing plasma viral
      loads, but not capable of inducing sterilizing immunity, may still provide
      substantial clinical benefits.

PMID- 11595291
TI  - Immune responses and reconstitution in HIV-1 infected individuals: impact of anti
      retroviral therapy, cytokines and therapeutic vaccination.
AB  - Most patients with chronic HIV-1 infection lack functional CD4(+) and CD8(+) HIV
      1-specific T cells with proliferative and cytolytic capacity, respectively. This
      is despite being able to produce intracellular cytokines in response to viral
      antigens. Protease inhibitor (PI)-based highly active anti-retroviral therapy
      (HAART) is unable to completely eradicate virus and fails to enable total
      restoration of immunity including induction of anti-HIV-1 responses. We have
      taken novel approaches towards the treatment of chronic HIV-1 disease with the
      aim of instigating long-term non-progressor status and depletion of virus
      reservoirs. HIV-1-specific CD4(+) and CD8(+) T cell responses were measured
      following the administration of cytokines, during therapeutic vaccination, and
      following treatment interruption (TI) or drug therapy change. Administration of
      cytokines, with or without therapeutic vaccination, in HAART treated patients,
      improved both CD4(+) and CD8(+) HIV-1-specific T cell responses even in late
      stage disease. Virus-specific T cell responses were also seen during TI or when
      transient viraemia was apparent, and following therapy change from a PI- to a non
      nucleoside-based HAART regimen. Reconstitution of HIV-1-specific immune responses
      was found to be transient and reversal to the previous anergic state was rapid.
      Viral reservoirs in the latently infected resting CD4(+) T cells, on follicular
      dendritic cells of germinal centers or even in infected thymic epithelium may be
      involved in clonal suppression and anergy. These may present major obstacles to
      the maintenance of HIV-1-specific responses and the eventual eradication of HIV
      1.

PMID- 11595292
TI  - Vaccination with CTL epitopes that escape: an alternative approach to HIV vaccine
      development?
AB  - This article describes a novel approach to HIV vaccine design that is, as yet,
      unproven and still in preliminary development. In rhesus macaques infected with
      simian immunodeficiency virus (SIV), we have identified particular cellular
      immune responses that select for viral variants during primary infection. We
      speculate that the detection of viral variants with altered amino acids in CTL
      epitopes implies the successful clearance of cells harboring wild-type virus.
      Here, we present our rationale suggesting why such potent early CTL responses
      that exert an antiviral effect may be particularly attractive targets for
      induction by candidate vaccines. Conventional wisdom suggests that regions of the
      virus that are structurally and functionally important will generally be well
      conserved both among clades and within an infected host. Amino acid replacements
      within these well-conserved regions should be difficult for the virus to
      accommodate. Therefore, these regions are traditionally considered ideal targets
      for vaccine induced immune responses because they are refractory to CTL escape
      mutations. Many examples of these regions have been identified in both HIV-1 and
      SIV(mac) (J. Immunol. 162 (1999) 3727; J. Virol. 67 (1993) 438) and have been
      included in candidate vaccine formulations. Human clinical trials testing these
      vaccines are currently underway. Our proposed method of vaccination with CTL
      epitopes that escape explores an alternative hypothesis. Rather than engendering
      responses to regions of the virus that do not escape, we reason that vaccination
      needs to accelerate the development of the initial immune responses that
      effectively select for amino acid variants during acute infection. By examining
      CTL escape during the acute phase, we will identify CTL responses that the virus
      cannot tolerate and incorporate these responses into vaccines.

PMID- 11595293
TI  - Analysis of the antigen specific T cell repertoires in HIV infection.
AB  - In addition to HIV infection, several acquired immunodeficiencies lead to
      depletion of CD4 lymphocytes. These include immunosuppression resulting from high
      dose cancer chemotherapy or induced to control graft rejection, as well as in
      autoimmune diseases. The consequence of this depletion is an increased
      susceptibility to opportunistic infections or the inability to control primary
      infection in the case of HIV infection. In all instances a full or partial
      immunoreconstitution is desirable. In order to monitor the cellular immune state
      of a patient, rational information cannot be simply derived from phenotypic
      quantification of T lymphocytes. Instead loss or recovery of CD4 cells should be
      monitored by defining the specificity, the function and the clonality of the
      relevant cell population. Several methods are now available for this type of
      investigation. Here we describe an approach for the definition of clonal
      heterogeneity of antigen specific CD4 lymphocytes, a parameter that may help
      monitor loss or reconstitution in acquired immunodeficiencies. As examples of
      antigen specific CD4 T cell responses we focused on Pneumocystis carinii and on
      cytomegalovirus, as prototypic opportunistic pathogens which are responsible for
      severe infections in AIDS and in other immunosuppressive conditions which arise
      for instance following transplantation. Specific CD4 T cell lines were generated
      from normal controls and from seropositives in order to select antigen specific
      lymphocytes. The cells were subsequently analyzed for clonal diversity according
      to TCR BV gene family usage and according to TCR CDR3 size heterogeneity
      (spectratyping).

PMID- 11595294
TI  - Analysis of the proliferative responses to peptides in individuals with vigorous
      Gag protein-specific proliferation.
AB  - Proliferative responses to recombinant HIV proteins in infected individuals may
      represent a correlate of protection from disease progression. In this study, the
      proliferative responses to HIV p24, p55 and gp120 were evaluated in infected
      subjects. Whereas, vigorous proliferative responses directed at the Gag proteins
      were detected in several individuals, Env-specific proliferation was observed in
      only one subject. Epitope mapping using overlapping peptides demonstrated
      proliferative responses of PBMC to Gag peptides. Responses were broadly directed
      at multiple peptides in some subjects. Although several of the peptides that
      induced proliferative responses also contain CTL epitopes potentially relevant in
      the particular individuals, many additional Gag T cell epitopes were present in
      each subject. This finding may be relevant for the design and testing of HIV
      candidate vaccines.

PMID- 11595295
TI  - Lipopeptide presentation pathway in dendritic cells.
AB  - Lipopeptides are currently being evaluated as candidate vaccines in human
      volunteers. They elicit cytotoxic responses from CD8(+) T lymphocytes, whereas
      peptides without a lipidic moiety usually do not. The exact processing and
      presentation pathways leading to association with MHC class I molecules has not
      yet been defined. This is of particular interest in dendritic cells, which are
      required for primary T cell stimulation. We have tracked lipopeptides derived
      from an HLA-A2.1-restricted HIV-1 Reverse Transcriptase epitope, by N-terminal
      addition of an N-epsilon-palmitoyl-lysine. Entry of the lipopeptides into human
      monocyte-derived dendritic cells (MDC) was mediated by endocytosis, as assessed
      by colocalization using analogs labelled with rhodamine, and by confocal
      microscopy. This internalization in DC induced functional stimulation of CD8(+) T
      lymphocytes specific for the epitopes, quantified by Interferon-gamma ELISPOT
      assays. The peptide alone was not visualized inside the DC and was only presented
      through direct surface association to HLA-A*0201. Therefore, lipopeptides provide
      a model system to define precisely the cross-presentation pathways that lead
      exogenous proteins to associate with class I MHC molecules within dendritic
      cells. Using this approach, cross-presentation pathways can be better defined and
      vaccine lipopeptides can be further optimized for MHC class I association in
      human dendritic cells.

PMID- 11595296
TI  - Rhesus macaque and chimpanzee DC-SIGN act as HIV/SIV gp120 trans-receptors,
      similar to human DC-SIGN.
AB  - Dendritic cells (DC) have been implicated in the pathogenesis of both human and
      simian immunodeficiency viruses (HIV and SIV, respectively). The DC-specific HIV
      1 trans-receptor DC-SIGN is thought to be essential for viral dissemination by
      DC. Abundant expression in lymphoid tissues also implies a function for DC-SIGN
      in chronic HIV-1 infections, in facilitating persistent infection of T cells. We
      have therefore isolated the rhesus macaque and chimpanzee homologues of DC-SIGN
      to investigate their function in a primate model. Both rhesus macaque and
      chimpanzee DC-SIGN are highly similar to the human homologue. Three monoclonal
      antibodies against human DC-SIGN, AZN-D1, -D2 and -D3, cross-react with rhesus
      macaque DC-SIGN, whereas AZN-D2 does not cross-react with chimpanzee DC-SIGN. The
      primate homologues are abundantly expressed in lymphoid tissues such as lymph
      nodes, as well as in mucosal tissues involved in sexual transmission of HIV-1,
      and are functionally similar to human DC-SIGN. They have a high affinity for the
      immunological ligands of DC-SIGN: ICAM-2 and -3. Moreover, both homologues bind
      the HIV-1 envelope glycoprotein gp120 and therefore can act as a HIV-1 trans
      receptor in the same way as human DC-SIGN. These data demonstrate that primate
      models are suitable to further dissect the role of DC-SIGN in the transmission
      and pathogenesis of infection with immunodeficiency viruses.

PMID- 11595297
TI  - Mother-to-child transmission of HIV infection and CTL escape through HLA-A2
      SLYNTVATL epitope sequence variation.
AB  - Cytotoxic T lymphocytes (CTL) play a central role in containment of HIV
      infection. Evasion of the immune response by CTL escape is associated with
      progression to disease. It is therefore hypothesised that transmitted viruses
      encode escape mutations within epitopes that are required for successful control
      of viraemia. In order to test this hypothesis, escape through the dominant HLA-A2
      restricted CTL epitope SLYNTVATL (p17 Gag residues 77-85 SL9) in the setting of
      mother-to-child-transmission (MTCT) was investigated. Initial data from two
      families in which the HIV-infected mother expressed HLA-A*0201 and had
      transmitted the virus to other family members were consistent with this
      hypothesis. In addition, analysis of the gag sequence phylogeny in one family
      demonstrated that CTL escape variants can be successfully transmitted both
      horizontally and vertically. To test the hypothesis further, a larger cohort of
      transmitting mothers (n=8) and non-transmitters (n=14) were studied. Variation
      within the SL9 epitope was associated with expression of HLA-A2 (P=0.04) but
      overall no clear link between variation from the SL9 consensus sequence and MTCT
      was established. However, the high level of background diversity within p17 Gag
      served to obscure any possible association between escape and MTCT. In
      conclusion, these studies highlighted the obstacles to demonstrating CTL escape
      arising at this particular epitope. Alternative strategies likely to be more
      definitive are discussed.

PMID- 11595298
TI  - Monitoring HIV-specific CD8+ T cell responses by intracellular cytokine
      production.
AB  - Human immunodeficiency virus (HIV)-specific CD8+ T cells play an important role
      in controlling HIV infection. Accurate monitoring of these cells is crucial in
      determining the effects of HIV therapy and vaccine efficacy. Using an
      intracellular cytokine staining based assay, we are able to directly quantify
      functional HIV-specific CD8+ T cells. This assay is highly reproducible, and can
      be performed using both fresh and cryopreserved peripheral blood cells.
      Importantly, this assay can be used to examine multiple HIV-peptide epitopes
      simultaneously, and is independent of patient HLA haplotype. Here, we examine the
      HIV-specific CD8+ T cell response to 95 optimized HIV-derived cytotoxic T
      lymphocyte (CTL) epitopes in 21 HIV-infected patients of varying HLA haplotype,
      using peptide mixes and matrices. We find that when using mixes of multiple HIV
      peptides, the CD8+ T cell response to the mixture is equivalent to the sum of the
      responses to the individual peptides contained therein. Detailed comparison of
      the responses in patients suggests that most patients generate a diverse CD8+ T
      cell response, recognizing multiple HIV epitopes derived from HIV Gag, Pol, Env,
      or Nef. Although some patients sharing HLA alleles occasionally recognize common
      peptides, rarely are responses to those peptides dominant within the same group
      of patients. These results confirm our previous findings that the responses to
      single HIV-peptides are rarely representative of the entire HIV response.

PMID- 11595299
TI  - The immunology of HIV-infected long-term non-progressors--a current view.
AB  - Long-term non-progressors (LTNP) are human immunodeficiency virus (HIV)-infected
      individuals characterized by the absence of disease, low viral loads and stable
      or even increasing CD4(+) T cell counts for prolonged periods of time. In these
      subjects, an HIV-specific immune response which is either stronger or directed
      against a wider array of viral epitopes than that seen in progressors, can be
      often detected. Here, we summarize the characteristics of HIV-specific CD4(+) and
      CD8(+) T cell responses in LTNP, and discuss how a highly effective T cell
      mediated immune response against HIV might contribute to the establishment of
      this particular condition.

PMID- 11595300
TI  - Considering genetic profiles in functional studies of immune responsiveness to
      HIV-1.
AB  - Over the last two decades HIV-1 has spread worldwide and has now surpassed
      malaria as the leading cause of infectious disease mortality in adults
      (http://www.who.int/infectious-disease-report/pages/ch1text.html). The clinical
      course and outcome of HIV-1 infection are highly variable among individuals. Most
      individuals infected with HIV develop AIDS within 10 years. However about 1-5%
      remain relatively healthy for 15 years or more (long-term nonprogressors), while
      others progress to AIDS within the first 2-3 years after infection (rapid
      progressors). A small number of individuals are resistant to infection, while
      some individuals appear to eliminate the virus. Factors that influence
      susceptibility to infection and rate of disease progression are a combination of
      viral, host, and environmental determinants. With few exceptions, genetic
      resistance to infectious diseases is likely to involve a complex array of host
      genetic effects involving variants that have very subtle, but significant
      consequences on gene expression or protein function. We have gained considerable
      insight into the genetic effects on HIV-1 disease, yet we likely have uncovered
      only a fraction of the total picture. The greater our knowledge of various
      effects on HIV disease, the more likely we will be able to predict disease
      outcome on an individual-by-individual basis. While this may seem obvious, there
      is no standard practice of taking into account the genetic profile (i.e.
      genotypes at loci known to associate with rate of AIDS progression) of subjects
      used in functional studies of immune responsiveness to HIV-1. Here, we propose an
      approach for assessing overall genetic risk on an individual basis, and suggest
      that this information be considered when selecting comparison groups in studies
      of immune responses to HIV and/or in the interpretation of data derived from such
      studies.

PMID- 11595301
TI  - Frequency and function of HIV-specific CD8(+) T cells.
AB  - The virus-specific CD8(+) T cell responses of 27 HIV-infected patients were
      studied, including a unique cohort of long term nonprogressors (LTNP) with normal
      CD4(+) T cell counts, low levels of plasma viral RNA, strong proliferative
      responses to HIV antigens and an over-representation of the HLA B*5701 class I
      allele. The frequencies of CD8(+) T cells specific to the majority of HIV gene
      products were measured by flow cytometric detection of intracellular interferon
      gamma (IFN-gamma) in response to HIV-vaccinia recombinant infected autologous B
      cells. Very high frequencies (1.4-22%) of circulating CD8(+) T cells were found
      to be HIV-specific and were not only found in LTNP with reduced plasma virus. No
      correlation was evident between the frequency of HIV-specific CD8(+) T cells and
      levels of plasma viremia. In each case, the vast majority of cells (up to 17.2%)
      responded to Gag-Pol gene products. Although similar frequencies of Gag peptide
      specific CD8(+) T cells were found in LTNP and progressors by either
      intracellular IFN-gamma or MHC class I tetramer staining, the breadth of these
      responses was greater in patients with progressive HIV infection compared with
      the LTNP group. The frequency of CD8(+) T cells specific for a single peptide was
      not representative of an individual patient's total HIV-specific CD8(+) T cell
      response. These data demonstrate that high numbers of HIV-specific CD8(+) T cells
      exist even in patients with high level viremia and progressive disease. Further,
      they suggest that other qualitative parameters of the CD8(+) T cell response may
      differentiate some patients with very low levels of plasma virus and
      nonprogressive infection.

PMID- 11595302
TI  - Human leucocyte antigen supertypes and immune susceptibility to HIV-1,
      implications for vaccine design.
AB  - T cell responses against HIV-1 have been identified in a number of exposed
      uninfected populations. We hypothesized that the ability to mount an effective T
      cell response is partly determined by the human leucocyte antigens (HLA)
      phenotype of the individual. We examined whether certain HLA supertypes were
      associated with differential HIV-1 susceptibility in sexually exposed adults and
      in the setting of mother to child HIV-1 transmission. By multivariate analysis,
      decreased HIV-1 infection risk was strongly associated with possession of a
      cluster of closely related class I HLA alleles (A2/6802 supertype) in sexually
      exposed adults (Hazard ratio=0.42, 95% confidence intervals (CI): 0.22-0.81,
      P=0.009) and perinatally exposed infants (Odds ratio=0.12, 95% CI: 0.03-0.54,
      P=0.006). The alleles in this HLA supertype are known in some cases, to present
      the same peptide epitopes (termed 'supertopes'), for T cell recognition. The
      identification of HIV-1 supertopes, which are associated with protection from HIV
      1 infection, has important implications for the application of epitope-based HIV
      l vaccines in a variety of racial groups.

PMID- 11595303
TI  - Sediment-associated tri-n-butyltin chloride and its effects on osmoregulation of
      freshwater-adapted 0-group European flounder, Platichthys flesus (L.).
AB  - The disruption of osmoregulatory processes was examined in European flounders
      exposed to environmental concentrations (150 ng TBTCl g(-1) dry weight sediment)
      of sediment-associated tri-n-butyltin chloride (TBTCl), by using radiotracers to
      measure changes in hydromineral fluxes and water balance. The water
      permeabilities of TBTCl-exposed fish varied during the course of the experiment
      and were significantly lower than those of the corresponding controls that did
      not change significantly with time. It was found that the maximum decrease in
      water permeability of TBTCl-exposed fish occurred after 14 days; thereafter there
      was an increase towards control values. However, there was a differential
      reduction of the diffusional (P(d)) and osmotic (P(os)) permeability
      coefficients, where the former decreased more rapidly than the latter, reflecting
      the reduction of diffusional membrane permeability and the increasing importance
      of osmotic permeability. In fish exposed to TBTCl sodium efflux and drinking
      rates were significantly increased but Na(+)/K(+)-ATPase activities and urine
      production rates were not affected. The effects of TBTCl exposure are also
      manifested at the level of the whole organism by a reduction in the increase of
      the body length of exposed fish, when compared to controls. It was concluded that
      tributyltin-n-chloride in sediments is capable of significantly disrupting the
      osmoregulatory functions of a benthic estuarine fish, at concentrations found in
      the sediments of Southampton Water and the River Itchen.

PMID- 11595304
TI  - Avoidance responses to aluminium in the freshwater bivalve Anodonta cygnea.
AB  - This study examined the effect of aluminium (Al) on the filtering behaviour
      (shell opening or gape) of the freshwater bivalve Anodonta cygnea L in neutral
      fresh water. Parallel measurements of Al concentration in the soft tissues were
      made to examine the relationship between changes in behaviour and accumulation of
      Al. The number of lysosomal granules in the gill, kidney and digestive gland were
      counted, as lysosomes are known to be involved in the excretion and
      detoxification of trace metals. The bivalves were exposed to two environmentally
      relevant concentrations of added Al i.e. 250 and 500 microg l(-1) (9.25 and 18.5
      microM l(-1)) at neutral pH for 15 days and shell movement monitored
      continuously. Aluminium affected the mussels' filtering activity, producing an
      avoidance reaction whose magnitude was concentration-dependent; 250 microg l(-1)
      added Al produced no detectable change, while 500 microg l(-1) Al reduced mean
      duration of shell opening by 50%. This effect was irreversible over a 15 day
      recovery period. Tissue levels of Al after 15 days exposure were an order of
      magnitude higher in animals exposed to 250 microg l(-1) added Al than in those
      exposed to 500 microg l(-1). This was consistent with the inhibition of filtering
      activity due to valve closure at the higher concentration, which may have
      prevented uptake of Al. In addition, probable different chemical speciation of Al
      in the water column (soluble for 250 and colloidal for 500 microg l(-1)) may lead
      to marked differences in tissue uptake. The kidney and digestive gland were the
      main sites of accumulation of Al and concentrations remained significantly
      elevated 15 days after transfer of animals to clean water. It is suggested that
      mucus plays a role in the exclusion of Al as elevated concentrations were
      measured in the pseudofaeces of animals during and after exposure. Lysosomal
      granules may be involved in the intracellular handling and detoxification of Al
      as numbers increased significantly in all organs during exposure and continued to
      increase after the animals were transferred to clean water. The present study
      provides evidence for the bioavailability and toxicity of Al to mussels at
      neutral pH and at concentrations which are known to enter neutral freshwaters
      when mobilised by natural or anthropogenic acidity. The changes in behaviour and
      uptake of Al in the mussel observed in this investigation are, therefore, likely
      to be reflected in the natural environment and the degree to which Al affects the
      'fitness' of the mussel populations and the transfer of Al through the food chain
      merit investigation.

PMID- 11595305
TI  - Toxicity of domoic acid in the marine mussel Mytilus edulis.
AB  - The neurotoxic, immunotoxic and genotoxic effects of domoic acid (DA) on the blue
      mussel Mytilus edulis were investigated by biomarkers, acethylcholinesterase
      (ChE) activity in gills, DNA fragmentation in digestive glands, vitality and
      phagocytosis activity of haemocytes in haemolymph of mussels. After intra
      muscular injection of DA at the concentrations ranging from 1-500 ng/g body
      weight (bw), no neurotoxic effect was detected within incubation times of 48 h
      and 7 d. The vitality of haemocytes remained in all mussels at the level of
      control samples within 48 h, and increased significantly after 7 d (P<0.05). At
      DA concentrations ranging from 1 to 100 ng/g bw haemocytes suggested a great
      phagocytosis activity, but no alteration in their number by both incubation
      times. By increasing DA concentration of 500 ng/g bw, the number of haemocytes
      doubled in 48 h without any change in phagocytosis activity. Primary DNA lesions
      in digestive glands of all injected mussels were determined in acute phase of
      poisoning within 48 h, and rapidly repaired after 7 d of incubation.

PMID- 11595307
TI  - Effect of cyanide concentrations on the secondary structures of protein in the
      crude homogenates of the fish gill tissue.
AB  - The effect of cyanide concentrations on the secondary conformation of protein in
      the fish gill homogenate was determined using an attenuated total reflectance
      (ATR)/Fourier transform infrared (FT-IR) microspectroscopy. Gills from male
      Tilapia zillii were isolated and homogenized in pH 8.0 Tris buffer solution and
      subjected to FT-IR study. The results indicate that the amide I and III bands of
      protein in fish gill homogenate deformed markedly with the increase of cyanide
      concentration. The fish gill homogenate shows a maximum peak at 1650 cm(-1) in
      amide I band, suggesting the predominant proportion of alpha-helical
      conformation. Once the KCN was added into the gill homogenate, the maximum peak
      shifted gradually from 1650 to 1643 cm(-1) due to the random coil structure, with
      the increase of cyanide concentration used. Two additional shoulders at 1657
      (alpha-helix) and 1627 (beta-sheet) cm(-1) also appeared gradually, implying that
      the cyanide can in part induce changes in protein conformation of fish gill
      homogenate from alpha-helix to random coil and beta-sheet conformations.

PMID- 11595306
TI  - P-glycoprotein in the catfish intestine: inducibility by xenobiotics and
      functional properties.
AB  - The p-glycoprotein (pgp)-mediated multixenobiotic resistance (MXR) mechanism of
      aquatic animals has been associated with protection against pollution. Recent
      studies in mammals suggest that intestinal pgp may modulate intestinal
      bioavailability of dietary xenobiotics. In order to further delineate this
      mechanism in the catfish, these studies: (1) examined the pgp-related
      distribution in the intestine and liver of catfish, (2) evaluated the MXR
      response following exposure to various dietary xenobiotics and a prototypic pgp
      inducer and (3) evaluated pgp functional activity in membrane vesicles, using
      prototypic substrates and inhibitors. For this purpose, catfish were exposed in
      vivo to the pgp inducer vincristine (VIN), and the xenobiotics beta
      naphthoflavone (BNF), benzo[a]pyrene (BaP), and 3,4,3',4'-tetrachlorobiphenyl
      (TCB). Membrane vesicles, prepared from liver and intestine (proximal and distal
      sections) of control and exposed catfish, were subjected to SDS PAGE, Western
      Blot, and detection with the pgp C219 monoclonal antibody. Transport activity was
      evaluated in vitro using the pgp substrate [3H]vinblastine (VBL), and the pgp
      inhibitor verapamil (VP). Immunoblot studies demonstrated a pgp-related protein
      of approximately 170 kDa in the intestine and liver of catfish. This protein
      appears to be very susceptible to degradation, and was present in higher levels
      in the liver, in comparison to the intestine, where regional differences were not
      observed. Dietary exposure to the pgp substrate VIN, or the xenobiotics BNF, BaP,
      and TCB, did not appear to affect pgp-related reactivity. Transport studies with
      VBL indicate that the pgp-related protein of the catfish intestine displays
      classic pgp-mediated multidrug resistance (MDR) characteristics, such as energy
      dependency, and sensitivity to VP. These studies suggest that the pgp-related
      protein in the catfish intestine and liver is not only immunochemically, but also
      functionally related to the mammalian MDR. Moreover, the results presented
      indicate that pgp-related reactivity and transport in intestinal vesicles of
      catfish may be influenced by factors including method sensitivity, sample
      collection, sample preparation, and immunoblot conditions.

PMID- 11595308
TI  - Environmental endocrine disruption in decapod crustacean larvae: hormone titers,
      cytochrome P450, and stress protein responses to heptachlor exposure.
AB  - A variety of enzymes and other proteins are produced by organisms in response to
      xenobiotic exposures. Cytochrome P450s (CYP) are one of the major phase I-type
      classes of detoxification enzymes found in terrestrial and aquatic organisms
      ranging from bacteria to vertebrates. One of the primary functions of stress
      proteins (HSPs) is to aid in the recovery of damaged proteins by chaperoning
      their refolding. These and other biomarkers of xenobiotic exposure and resulting
      effects have not been studied in crustacean larvae. This information is of
      potential importance for environmental management and risk assessment. In this
      work, we have given Homarus americanus larvae single 24 h exposures to the
      cyclodiene pesticide heptachlor, a known environmental endocrine disruptor (EDC)
      on different days of the 1st larval instar. We followed these larvae during the
      first larval stage for effects on timing of ecdysis to 2nd stage, ecdysteroid
      molting hormone titers, and alterations in the levels of cytochrome P450 CYP45
      and HSP70 proteins. Delays in ecdysis were correlated with alterations in
      ecdysteroid levels. This result provides clues that this pesticide may function
      as an environmental endocrine disruptor in crustaceans. CYP45 and HSP70 levels
      were significantly elevated for several days following heptachlor exposure. The
      elevation in HSP70 was prolonged depending on the day of pesticide exposure and
      this was directly related to the increase in mortality. These results demonstrate
      the utility of these measurements as potential biomarkers in crustacean larval
      developmental toxicology and EDC effects research.

PMID- 11595309
TI  - Effects of tributyltin and other metals on the phenoloxidase activating system of
      the tunicate, Styela plicata.
AB  - Toxic metals, such as tributyltin (TBT), contribute substantially to
      anthropogenic pollution in many estuarine environments. Animals that live in
      those environments, particularly invertebrate filter feeders like tunicates, are
      likely to be exposed to substantial metal contamination. This study investigates
      the effects of TBT and other metals on the phenoloxidase activity of the
      estuarine tunicate, Styela plicata, in an effort to identify a biochemical marker
      of metal pollution. Hemocytes harvested from S. plicata that were exposed to
      tributyltin or copper in aquaria had significantly enhanced phenoloxidase
      activities relative to non-exposed controls. This enhanced phenoloxidase activity
      could be explained by an increased frequency of morula cells, which contain high
      levels of phenoloxidase's proenzyme, prophenoloxidase. Unlike those from
      tunicates exposed to metals in aquaria, the phenoloxidase activities of hemocytes
      incubated with tributyltin in vitro were significantly reduced when compared with
      hemocytes cultured without tributyltin. The ability of tributyltin to decrease
      phenoloxidase activity in tissue culture may reflect its known inhibitory effects
      on calcium-dependent signaling systems such as those involved in the exocytosis
      of prophenoloxidase from morula cells.

PMID- 11595310
TI  - Relationships between tissue contaminants and defense-related characteristics of
      oysters (Crassostrea virginica) from five Florida bays.
AB  - Evidence linking bivalve defense responses with pollutant exposure is increasing.
      Contaminant effects on immune or defense responses could influence the ability of
      an organism to resist infectious disease. This study explored relationships
      between xenobiotic chemicals accumulated in oyster (Crassostrea virginica) tissue
      and various measures of putative oyster internal defense activities and
      physiological condition. Defense-related and physiological measurements were made
      on individual oysters collected from 22 sites at five Florida bays and pooled
      oyster tissue from each site was analyzed for polycyclic aromatic hydrocarbons
      (PAHs), polychlorinated biphenyls (PCBs), metals and certain pesticides. Chemical
      concentrations, physiological condition, and hemocyte and hemolymph
      characteristics varied across bays and among sites within a bay. Within-bay
      comparisons showed that sites with high oyster defense-related activities often
      had accompanying high tissue concentrations of one or more classes of xenobiotic
      chemicals. Correlation analysis performed across bays demonstrated significant
      positive relationships between most defense-related characteristics and at least
      one contaminant, including various PAH, PCB and trace metal analytes. In
      combination with other recent studies, these results strengthen the hypothesis
      that certain xenobiotic chemicals may be associated with elevated oyster hemocyte
      activities, even though the ultimate influence on disease resistance remains
      unknown.

PMID- 11595312
TI  - Effects of atrazine on periphyton under grazing pressure.
AB  - An experiment was carried out using indoor experimental channels to assess the
      long-term effect (18 days) of herbivores (Physella acuta, Gastropoda) on
      periphyton communities exposed to low levels of atrazine (14 microg l(-1)). We
      hypothesized that herbivorism modifies the response of periphyton to atrazine.
      Carbon incorporation, chlorophyll-a content, biovolume and algal taxonomic
      composition in the channels that contained atrazine were not significantly
      different from the control channels (not receiving atrazine). In channels with
      grazers and atrazine, there was a significant reduction of carbon incorporation
      and algal density. In this treatment, physiognomic forms and algal composition
      were significantly different from the others. The biomass of grazers (measured as
      change in dry mass) was not significantly affected by the addition of atrazine.
      Grazers maintained low levels of periphyton biomass, enhancing algal cell
      exposition to toxicant and inhibiting any adaptation of the algae to the toxic
      exposure. The increase in atrazine toxicity with grazing not only affected the
      metabolism, but also the structure of the algal community, which suggests that
      effects were not transient but permanent.

PMID- 11595311
TI  - Decreased glutathione S-transferase expression and activity and altered sex
      steroids in Lake Apopka brown bullheads (Ameiurus nebulosus).
AB  - A number of freshwater lakes and reclaimed agricultural sites in Central Florida
      have been the receiving waters for agrochemical and municipal runoff. One of
      these sites, Lake Apopka, is also a eutrophic system that has been the focus of
      several case studies reporting altered reproductive activity linked to
      bioaccumulation of persistent organochlorine chemicals in aquatic species. The
      present study was initiated to determine if brown bullheads (Ameiurus nebulosus)
      from the north marsh of Lake Apopka (Lake Apopka Marsh) exhibit an altered
      capacity to detoxify environmental chemicals through hepatic glutathione S
      transferase (GST)-mediated conjugation as compared with bullheads from a nearby
      reference site (Lake Woodruff). We also compared plasma sex hormone
      concentrations (testosterone, 17-beta estradiol, and 11 keto-testosterone) in
      bullheads from the two sites. Female bullheads from Lake Apopka had 40% lower
      initial rate GST conjugative activity toward 1-chloro-2,4-dinitrobenzene (CDNB),
      50% lower activity towards p-nitrobutyl chloride (NBC), 33% lower activity toward
      ethacrynic acid (ECA), and 43% lower activity toward Delta5-androstene-3,17-dione
      (Delta(5)-ADI), as compared with female bullheads from Lake Woodruff. Enzyme
      kinetic analyses demonstrated that female bullheads from Lake Apopka had lower
      GST-catalyzed CDNB clearance than did female Lake Woodruff bullheads. Western
      blotting studies of bullhead liver cytosolic proteins demonstrated that the
      reduced GST catalytic activities in female Lake Apopka bullheads were accompanied
      by lower expression of hepatic GST protein. No site differences were observed
      with respect to GST activities or GST protein expression in male bullheads.
      Female Lake Apopka bullheads also had elevated concentrations of plasma androgens
      (testosterone and 11-ketotestosterone) as compared with females from Lake
      Woodruff. In contrast, male Lake Apopka bullheads had elevated levels of plasma
      estrogen but similar levels of androgens as compared with male bullheads from
      Lake Woodruff. Collectively, our studies indicate the presence of reduced GST
      protein expression, reduced GST conjugative capacity and altered sex steroid
      homeostasis in female bullheads from a contaminated field site in Central
      Florida. The implications of these physiological alterations in terms of
      pollutant biotransformation and reproduction are discussed.

PMID- 11595314
TI  - Relaxations and fluctuations in myoglobin.
AB  - One major goal of biological physics is the discovery and understanding of the
      concepts and laws that govern biomolecules, in particular proteins. Since there
      exist at least 10(5) different proteins, the choice of a suitable prototype is
      necessary. Myoglobin (Mb) has for many years played the role of such a prototype.
      It appears to be simple enough so that many of its properties can be understood,
      yet it is complex enough to display many of the fascinating characteristics of
      biomolecules. One major achievement in the study of any protein would be the
      establishment of convincing connections among structure, kinetics, energy
      landscape, dynamics, and function. We believe that this goal has not yet been
      reached in any protein, but the present knowledge of Mb gives some hope that the
      end is near in this case. Here, we sketch some of the results that have been
      obtained in the past 50 or more years in the research on Mb, obtained by an army
      of investigators.

PMID- 11595315
TI  - Free radical transfer, fluctuating structure and reaction cycle of ribonucleotide
      reductase.
AB  - Our understanding of the nature and functional importance of protein dynamics is
      based on experimental and theoretical work on rather 'simple' systems. Here, the
      principles of the fluctuating structure of a protein is applied to the complex
      enzyme ribonucleotide reductase (RNR). This enzyme contains a stable tyrosyl
      radical, which is a strong oxidant. The radical initiates the enzymatic reaction
      by oxidizing the ribose moeity of the substrate, bound at a distance of ca. 35 A
      away from the tyrosine harboring the radical. The transfer of the oxidation
      equivalent, the electron hole, requires a chain of overlapping electronic
      orbitals along the route, and is made energetically possible by the simultaneous
      switching of a series of H-bonds, making the transfer charge neutral. Only a
      fraction of the enormous number of accessible protein substates support this
      transfer. The probability of an enzyme molecule to obtain such a substate by
      thermal fluctuations is negligible, except for the case of a complete enzyme with
      bound substrate. When the radical has been transferred to the ribose, its 2'-OH
      is immediately reduced to 2'-H by the enzyme, and the electron hole goes back via
      the chains of orbital overlaps and H-bonds. This model is capable to explain all
      known kinetic properties of the wild type enzyme and its mutated forms. The
      analogy between this model of how the fluctuating protein structure controls and
      makes the radical transfer possible in RNR and recent ideas about the mechanism
      of the anomalously fast proton conduction in liquid water is considered.

PMID- 11595316
TI  - Non-stationary fluctuation analysis of the Na current in myelinated nerve fibers
      of Xenopus laevis: experiments and stochastic simulations.
AB  - Na current fluctuations under voltage-clamp conditions during pulse steps in the
      potential range from -65 to -30 mV were measured in myelinated nerve fibers of
      Xenopus laevis. The covariance functions for four consecutive 1 ms intervals were
      calculated. The time courses of the covariance functions were well fitted with
      monoexponential functions with time constants between 0.5 and 3 ms, larger at the
      end of the pulse and larger at more positive potentials. To analyze the
      underlying channel kinetics we simulated current fluctuations at a step to -35 mV
      of eight published Na channel models and calculated corresponding covariance
      functions. None of the models did explain the experimental fluctuation results.
      We therefore developed a new Na channel model that satisfactorily described the
      results. Features that distinguished this model from the other tested ones were a
      slower deactivation rate, and an inactivation transition directly from a closed
      state.

PMID- 11595317
TI  - Na channel kinetics: developing models from non-stationary current fluctuations
      by analytic methods.
AB  - In a previous study, we analyzed Na current fluctuations in myelinated axons from
      Xenopus laevis under voltage clamp conditions. The statistical properties were
      analyzed in terms of covariance functions for consecutive time intervals of
      varying duration during the pulse step. The underlying channel kinetics was
      analyzed by performing stochastic simulations of published Na channel models and
      calculating corresponding covariance functions. None of the models explained the
      fluctuation results. We therefore developed a novel minimal Na channel model that
      satisfactorily described the results. In the present paper, we extend the
      analysis and specify the possible models explaining the experimental data by
      using analytical methods. We derive general relations between the experimental
      data, including the covariance functions, and the rate constants of specific one
      open-state models. A general feature of these models is that they comprise an
      inactivation step from the first closed state and a relatively low backward rate
      from the open state. This is in accordance the minimal model inferred from
      numerical stochastic calculations in the previous study.

PMID- 11595318
TI  - Comparing fluctuations of synaptic responses mediated via AMPA and NMDA receptor
      channels--implications for synaptic plasticity.
AB  - Glutamate-releasing synapses are essential in fast neuronal signalling.
      Plasticity at these synapses is important for learning and memory as well as for
      the activity-dependent control of neuronal development. We have evaluated the
      trial-to-trial fluctuations of excitatory postsynaptic currents mediated by
      glutamate receptors of the AMPA and NMDA types in CA1 pyramidal cells. By using
      the whole cell patch clamp technique in brain slices from young rats, we have
      demonstrated that the relative variability of AMPA and NMDA receptor mediated
      responses, expressed as the coefficient of variation, is similar for these two
      types of responses [Brain Res. 800 (1998) 253-259]. The present paper summarizes
      and discusses these results in relation to current theories on hippocampal
      synaptic plasticity, especially with regard to the ideas of glutamate spillover
      and silent synapses. Our finding of a correspondence between AMPA and NMDA
      responses with respect to fluctuations is compatible with our previous finding of
      equal relative changes of the two during activity induced synaptic plasticity.
      However, the results argue against the glutamate spillover model according to
      which the effect of glutamate--and hence the induction of plasticity--may spread
      unspecifically between synapses. But how can silent synapses become functional if
      no spread of glutamate occurs and no initial signal is present to trigger the
      functionalization? Is it necessary that NMDA responses are present at these
      synapses, which are then silent merely with respect to AMPA receptors, or do
      other alternatives exist? Our discussion aims to elucidate these questions.

PMID- 11595320
TI  - Cell motility and thermodynamic fluctuations tailoring quantum mechanics for
      biology.
AB  - Cell motility underlying muscle contraction is an instance of thermodynamics
      tailoring quantum mechanics for biology. Thermodynamics is intrinsically multi
      agential in admitting energy consumers in the form of energy-deficient
      thermodynamic fluctuations. The onset of sliding movement of an actin filament on
      myosin molecules in the presence of ATP molecules to be hydrolyzed demonstrates
      that thermodynamic fluctuations transform their nature so as to accommodate
      themselves to energy transduction subject to the first law of thermodynamics. The
      transition from transversal to longitudinal fluctuations of an actin filament
      with the increase of ATP concentration coincides with the change in the nature of
      energy consumers acting upon thermal energy in the light of the first law,
      eventually embodying a uniform sliding movement of an actin filament.

PMID- 11595319
TI  - Single-file diffusion and neurotransmitter transporters: Hodgkin and Keynes model
      revisited.
AB  - Norepinephrine transporters (NETs) use the Na gradient to remove norepinephrine
      (NE) from the synaptic cleft of adrenergic neurons following NE release from the
      presynaptic terminal. By coupling NE to the inwardly directed Na gradient, it is
      possible to concentrate NE inside cells. This mechanism, which is referred to as
      co-transport or secondary transport (Lauger, 1991, Electrogenic Ion Pumps,
      Sinauer Associates) is apparently universal: Na coupled transport applies to
      serotonin transporters (SERTs), dopamine transporters (DATs), glutamate
      transporters, and many others, including transporters for osmolites, metabolites
      and substrates such as sugar. Recently we have shown that NETs and SERTs
      transport norepinephrine or serotonin as if Na and the transmitter permeated
      through an ion channel together 'Galli et al., 1998, PNAS 95, 13260-13265;
      Petersen and DeFelice, 1999, Nature Neurosci. 2, 605-610'. These data are
      paradoxical because it has been difficult to envisage how NE, for example, would
      couple to Na if these ions move passively through an open pore. An 'alternating
      access' model is usually evoked to explain coupling: in such models NE and Na
      bind to NET, which then undergoes a conformational change to release NE and Na on
      the inside. The empty transporter then turns outward to complete the cycle.
      Alternating-access models never afford access to an open channel. Rather,
      substrates and co-transported ions are occluded in the transporter and carried
      across the membrane. The coupling mechanism we propose is fundamentally different
      than the coupling mechanism evoked in the alternating access model. To explain
      coupling in co-transporters, we use a mechanism first evoked by 'Hodgkin and
      Keynes (1955) J. Physiol. 128, 61-88' to explain ion interactions in K-selective
      channels. In the Hodgkin and Keynes model, K ions move single-file through a long
      narrow pore. Their model accounted for the inward/outward flux ratio if they
      assumed that two K ions queue within the pore. We evoke a similar model for the
      co-transport of transmitter and Na. In our case, however, coupling occurs not
      only between like ions but also between unlike ions (i.e. the transmitter and Na
      ). We made a replica of the Hodgkin and Keynes mechanical model to test our
      ideas, and we extended the model with computer simulations using Monte Carlo
      methods. We also developed an analytic formula for Na coupled co-transport that
      is analogous to the single-file Ussing equation for channels. The model shows
      that stochastic diffusion through a long narrow pore can explain coupled
      transport. The length of the pore amplifies the Na gradient that drives co
      transport.

PMID- 11595321
TI  - Variability and coding efficiency of noisy neural spike encoders.
AB  - Encoding synaptic inputs as a train of action potentials is a fundamental
      function of nerve cells. Although spike trains recorded in vivo have been shown
      to be highly variable, it is unclear whether variability in spike timing
      represents faithful encoding of temporally varying synaptic inputs or noise
      inherent in the spike encoding mechanism. It has been reported that spike timing
      variability is more pronounced for constant, unvarying inputs than for inputs
      with rich temporal structure. This could have significant implications for the
      nature of neural coding, particularly if precise timing of spikes and temporal
      synchrony between neurons is used to represent information in the nervous system.
      To study the potential functional role of spike timing variability, we estimate
      the fraction of spike timing variability which conveys information about the
      input for two types of noisy spike encoders--an integrate and fire model with
      randomly chosen thresholds and a model of a patch of neuronal membrane containing
      stochastic Na(+) and K(+) channels obeying Hodgkin-Huxley kinetics. The quality
      of signal encoding is assessed by reconstructing the input stimuli from the
      output spike trains using optimal linear mean square estimation. A comparison of
      the estimation performance of noisy neuronal models of spike generation enables
      us to assess the impact of neuronal noise on the efficacy of neural coding. The
      results for both models suggest that spike timing variability reduces the ability
      of spike trains to encode rapid time-varying stimuli. Moreover, contrary to
      expectations based on earlier studies, we find that the noisy spike encoding
      models encode slowly varying stimuli more effectively than rapidly varying ones.

PMID- 11595322
TI  - Noise-induced impulse pattern modifications at different dynamical period-one
      situations in a computer model of temperature encoding.
AB  - We used a minimal Hodgkin-Huxley type model of cold receptor discharges to
      examine how noise interferes with the non-linear dynamics of the ionic mechanisms
      of neuronal stimulus encoding. The model is based on the assumption that spike
      generation depends on subthreshold oscillations. With physiologically plausible
      temperature scaling, it passes through different impulse patterns which, with
      addition of noise, are in excellent agreement with real experimental data. The
      interval distributions of purely deterministic simulations, however, exhibit
      considerable differences compared to the noisy simulations especially at the
      bifurcations of deterministically period-one discharges. We, therefore, analyzed
      the effects of noise in different situations of deterministically regular period
      one discharges: (1) at high-temperatures near the transition to subthreshold
      oscillations and to burst discharges, and (2) at low-temperatures close to and
      more far away from the bifurcations to chaotic dynamics. The data suggest that
      addition of noise can considerably extend the dynamical behavior of the system
      with coexistence of different dynamical situations at deterministically fixed
      parameter constellations. Apart from well-described coexistence of spike
      generating and subthreshold oscillations also mixtures of tonic and bursting
      patterns can be seen and even transitions to unstable period-one orbits seem to
      appear. The data indicate that cooperative effects between low- and high
      dimensional dynamics have to be considered as qualitatively important factors in
      neuronal encoding.

PMID- 11595323
TI  - A communication channel model for information transmission in the blowfly
      photoreceptor.
AB  - Biological photoreceptors transduce and communicate information about visual
      stimuli to other neurons through a series of signal transformations among
      physical states such as concentration of a chemical species, current, or the
      number of open ion channels. We present a communication channel model to quantify
      the transmission and degradation of visual information in the blowfly
      photoreceptor cell. The model is a cascade of linear transfer functions and noise
      sources that are derived from fundamental principles whenever possible, and whose
      parameters are estimated from physiological data. We employ the model to
      calculate the information capacity of blowfly phototransduction; our results
      compare favorably with estimates of the capacity derived from experimental
      measurements by de Ruyter van Steveninck and Laughlin (Nature 379 (1996) 642-645)
      and Juusola (J. Gen. Physiol. 104 (1994) 593-621). The model predicts that photon
      shot noise and ion channel noise are the dominant noise sources that limits
      information transmission in the blowfly photoreceptor.

PMID- 11595325
TI  - Bifurcation structure of a model of bursting pancreatic cells.
AB  - One- and two-dimensional bifurcation studies of a prototypic model of bursting
      oscillations in pancreatic beta-cells reveal a squid-formed area of chaotic
      dynamics in the parameter plane, with period-doubling bifurcations on one side of
      the arms and saddle-node bifurcations on the other. The transition from this
      structure to the so-called period-adding structure is found to involve a
      subcritical period-doubling bifurcation and the emergence of type-III
      intermittency. The period-adding transition itself is not smooth but consists of
      a saddle-node bifurcation in which (n+1)-spike bursting behavior is born,
      slightly overlapping with a subcritical period-doubling bifurcation in which n
      spike bursting behavior loses its stability.

PMID- 11595326
TI  - Delay, noise and phase locking in pulse coupled neural networks.
AB  - This paper studies the effect of several delay times and noise on the stability
      of the phase-locked state in the lighthouse model and the integrate and fire
      model of a pulse coupled neural network. The coupling between neurons may be
      arbitrary. In both models the increase of delay times leads to a weakening of the
      stability and to the occurrence of relaxation oscillations.

PMID- 11595327
TI  - Reinforcement learning with internal expectation in the random neural networks
      for cascaded decisions.
AB  - The reinforcement learning scheme proposed in Halici (J. Biosystems 40 (1997) 83)
      for the random neural network (RNN) (Neural Computation 1 (1989) 502) is based on
      reward and performs well for stationary environments. However, when the
      environment is not stationary it suffers from getting stuck to the previously
      learned action and extinction is not possible. To overcome the problem, the
      reinforcement scheme is extended in Halici (Eur. J. Oper. Res., 126(2000) 288) by
      introducing a new weight update rule (E-rule) which takes into consideration the
      internal expectation of reinforcement. Although the E-rule is proposed for the
      RNN, it can be used for training learning automata or other intelligent systems
      based on reinforcement learning. This paper looks into the behavior of the
      learning scheme with internal expectation for the environments where the
      reinforcement is obtained after a sequence of cascaded decisions. The simulation
      results have shown that the RNN learns well and extinction is possible even for
      the cases with several decision steps and with hundreds of possible decision
      paths.

PMID- 11595328
TI  - Population oscillations in a discrete model of neural networks of the brain.
AB  - A discrete model of biological neural networks is used to find out how
      synchronized firing of neurons emerges in a randomly connected neural population.
      The objective is to understand the mechanisms underlying brain waves and to find
      and characterize conditions which support spontaneous switching from disordered
      to rhythmic population activity as in case of an epileptic seizure. The model is
      kept as simple as possible to achieve on one hand a fast performance of computer
      simulations of networks with up to 10,000 neurons and to keep on the other hand
      an overview of parameter dependences. Dynamics of the model can be classified
      into different regimes: random fluctuations, rhythmic oscillations and silence.
      When the ratio of the inhibitory/excitatory connectivity is raised the system
      crosses from the fluctuating regime through the rhythmic oscillating region to
      the silence regime. Close to the boundary between the fluctuating and the
      oscillating regimes the network shows spontaneous bursting of high amplitude
      rhythmic oscillations, which is characteristic of epileptiform behavior. The
      simulation results are in agreement with recent theories saying that focal
      epilepsy after injury of the brain could result from axonal sprouting of
      GABAergic neurons in the injured region.

PMID- 11595329
TI  - Effects of non-synaptic neuronal interaction in cortex on synchronization and
      learning.
AB  - During neural communication by means of action potentials, small electromagnetic
      (EM) fields are also generated. We use a three layered cortical neural network
      model to study the effects of EM fields and gap junctions on spatio-temporal
      network activity. We investigate the possible role of these effects in
      synchronizing activity, a phenomenon which has been observed in the olfactory
      cortex and the hippocampus. The simulation results support the notion that fast
      synchronization of activity in distant parts of the neural network are made
      possible by means of EM fields and/or gap junctions. The results also indicate
      that these effects, to a certain extent, are beneficial to system performance.

PMID- 11595330
TI  - Spontaneously active cells induce state transitions in a model of olfactory
      cortex.
AB  - The existence of neurons with intrinsic oscillations does not in itself explain
      the synchronization of local populations of neurons, but it is likely to pace
      population rhythms when the neurons are suitably coupled by chemical and/or
      electrical synapses. In the present study, we have investigated the role of
      spontaneously active cells as noisy or pacemaker units in setting global
      oscillations in a three-layered cortical model. The presence of a small number of
      noisy (spontaneously active) units induce oscillations at the network level in
      the range of the gamma rhythm. The number of noisy units in the network and their
      type (excitatory or inhibitory or excitatory and inhibitory together) determines
      the emergence of regular oscillations or aperiodic (chaotic) behaviour. It also
      determines the onset of the global behaviour. On replacing a noisy unit by a
      pacemaker unit, similar gamma oscillations were generated. With both noisy and
      pacemaker units, we found that certain characteristics of the spontaneous
      activity determine the delay period for the onset of global activity. Preliminary
      studies have been carried out with spontaneously active units having a chaotic
      dynamics but the results are much similar to that with a noisy burst. Different
      functional roles have been suggested for cortical oscillations, such as
      determining global functional states and specifying connectivity during
      development. Oscillations at different frequency bands, in particular in the
      gamma band (around 40 Hz), have also been associated with memory and attention.
      The presence of spontaneously active neurons, either with noisy or oscillatory
      activity, could be responsible for global oscillations in the absence of external
      stimuli in certain cortical areas in the mature brain.

PMID- 11595331
TI  - Toward an integrated continuum model of cerebral dynamics: the cerebral rhythms,
      synchronous oscillation and cortical stability.
AB  - Continuum models of cerebral cortex with parameters derived from physiological
      data, provide explanations of the cerebral rhythms, synchronous oscillation, and
      autonomous cortical activity in the gamma frequency range, and suggest possible
      mechanisms for dynamic self-organization in the brain. Dispersion relations and
      derivations of power spectral response for the models, show that a low frequency
      resonant mode and associated travelling wave solutions of the models' equations
      of state can account for the predominant 1/f spectral content of the
      electroencephalogram (EEG). Large scale activity in the alpha, beta, and gamma
      bands, is accounted for by thalamocortical interaction, under regulation by
      diffuse cortical excitation. System impulse responses can be used to model Event
      Related Potentials. Further classes of local resonance may be generated by rapid
      negative feedbacks at active synapses. Activity in the gamma band around 40 Hz,
      associated with large amplitude oscillations of pulse density, appears at higher
      levels of cortical activation, and is unstable unless compensated by synaptic
      feedbacks. Control of cortical stability by synaptic feedbacks offers a partial
      account of the regulation of autonomous activity within the cortex. Synchronous
      oscillation occurs between concurrently excited cortical sites, and can be
      explained by analysis of wave motion radiating from each of the co-active sites.
      These models are suitable for the introduction of learning rules-most notably the
      coherent infomax rule.

PMID- 11595332
TI  - Changes in power and coherence of brain activity in human sensorimotor cortex
      during performance of visuomotor tasks.
AB  - Electrocorticograms (ECoG) were recorded using subdural grid electrodes in
      forearm sensorimotor cortex of six human subjects. The subjects performed three
      visuomotor tasks, tracking a moving visual target with a joystick-controlled
      cursor; threading pieces of tubing; and pinching the fingers sequentially against
      the thumb. Control conditions were resting and active wrist extension. ECoGs were
      recorded at 14 sites in hand- and arm-sensorimotor area, functionally identified
      with electrical stimulation. For each behavior we computed spectral power of ECoG
      in each site and coherence in all pair-wise sites. In three out of six subjects,
      gamma-oscillations were observed when the subjects started the tasks. All
      subjects showed widespread power decrease in the range of 11-20 Hz and power
      increase in the 31-60 Hz ranges during performance of the visuomotor tasks. The
      changes in gamma-range power were more vigorous during the tracking and threading
      tasks compared with the wrist extension. Coherence analysis also showed similar
      task-related changes in coherence estimates. In contrast to the power changes,
      coherence estimates increased not only in gamma-range but also at lower
      frequencies during the manipulative visuomotor tasks. Paired sites with
      significant increases in coherence estimates were located within and between
      sensory and motor areas. These results support the hypothesis that coherent
      cortical activity may play a role in sensorimotor integration or attention.

PMID- 11595333
TI  - Are attractors 'strange', or is life more complicated than the simple laws of
      physics?
AB  - Interesting and intriguing questions involve complex systems whose properties
      cannot be explained fully by reductionist approaches. Last century was dominated
      by physics, and applying the simple laws of physics to biology appeared to be a
      practical solution to understand living organisms. However, although some
      attributes of living organisms involve physico-chemical properties, the genetic
      program and evolutionary history of complex biological systems make them unique
      and unpredictable. Furthermore, there are and will be 'unobservable' phenomena in
      biology which have to be accounted for.

PMID- 11595334
TI  - Cellular localization of metabotropic glutamate receptors mGluR1, 2/3, 5 and 7 in
      the main and accessory olfactory bulb of the rat.
AB  - The cellular localization of metabotropic glutamate receptors (mGluRs)
      (mGluR1alpha, 2/3, 5a and 7) in the main and accessory olfactory bulb (MOB and
      AOB) of adult rats was compared by using affinity purified polyclonal antibodies
      directed to their C-termini. mGluR1alpha and mGluR5a immunoreactivities were
      located in comparable structures of the MOB and AOB with different levels of
      intensity. mGluR5a reactivity was high in the AOB. mGluR2/3 showed a different
      pattern of expression in the MOB compared to that observed in the AOB; the
      periglomerular region of the MOB was strongly stained, but in the AOB it was the
      mitral/tufted cell layer that was intense. The mitral cell bodies in the MOB were
      strongly immunoreactive for mGluR7. These differences in the distribution of
      mGluRs in the MOB and AOB may reflect differences in synaptic transmission and
      sensitivity to neuromodulation in the two systems.

PMID- 11595335
TI  - Electroacupuncture-related changes of NADPH-diaphorase and neuronal nitric oxide
      synthase in the brainstem of spontaneously hypertensive rats.
AB  - The aim of this study was to investigate the electroacupuncture-related changes
      of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) and neuronal
      nitric oxide synthase (nNOS) in the brainstem of spontaneously hypertensive rats
      (SHR). We evaluated the changes of NADPH-d-positive neurons using a histochemical
      method and the changes of nNOS-positive neurons using an immunohistochemical
      method. The staining intensities of NADPH-d-positive neurons and nNOS-positive
      neurons were assessed in a quantitative fashion using a microdensitometrical
      method based on optical density by means of an image analyzer. The optical
      density of NADPH-d-positive neurons and nNOS-positive neurons of the Shinsu
      (BL23) and Choksamni (ST36) electroacupuncture groups were significantly
      decreased in most brainstem areas as compared to the normal and arbitrary groups,
      with the exception of the optical density of NADPH-d positive neurons in the
      prepositus nucleus as compared to the arbitrary group. The present results
      demonstrated that electroacupuncture changes the activity in the NO system in the
      brainstem of SHR and the site where electroacupuncture is administered is of
      importance for this effect.

PMID- 11595336
TI  - Evidence that the HIV-1 coat protein gp120 causes neuronal apoptosis in the
      neocortex of rat via a mechanism involving CXCR4 chemokine receptor.
AB  - The HIV-1 coat protein, gp120 (100 ng given intracerebroventricularly (i.c.v.)
      daily for seven consecutive days) causes DNA fragmentation in the brain neocortex
      of rat. In neocortical cells bearing ultrastructural features typical of
      apoptosis, electron microscopy revealed specific immunopositivity for
      neurofilament cytoskeletal proteins, suggesting the neuronal nature of dying
      cells. Neuronal apoptosis by gp120 implicates CXCR4 chemokine receptors; in fact,
      in rats receiving a single daily, non-neurotoxic, dose of SDF-1alpha (0.25 pmoles
      given i.c.v. for 7 days before gp120), the natural ligand of CXCR4 receptor,
      apoptosis was significantly hindered. The mechanism of SDF-1alpha protection
      involves inhibition of gp120-enhanced expression of IL-1beta, a cytokine
      implicated in the mechanisms of apoptosis induced by the viral protein in the
      neocortex of rat.

PMID- 11595337
TI  - A novel mutation in glial fibrillary acidic protein gene in a patient with
      Alexander disease.
AB  - Alexander disease is a rare, progressive, leukoencephalopathy whose hallmark is
      the widespread accumulation of Rosenthal fibers. The most common form affects
      infants and young children, and is characterized by progressive failure of
      central myelination, usually leading to death before adulthood. Definitive
      diagnosis of Alexander disease has required biopsy or autopsy to demonstrate the
      presence of Rosenthal fibers. However, missense mutations in the coding region of
      the glial fibrillary acidic protein (GFAP) gene have recently been associated
      with a high percentage of pathologically proven cases. Here we report that a 10
      year-old Japanese patient who showed clinical signs of Alexander disease is
      heterozygous for a C to T transition in which predicts a novel A244V amino acid
      substitution in the conserved 2A alpha-helix domain of GFAP. The nucleotide
      change was not found in 65 normal individuals (130 alleles). These results
      provide further support for a causative role for GFAP mutations in Alexander
      disease, and suggest DNA sequencing as an alternative diagnostic to biopsy.

PMID- 11595338
TI  - Hyperthermia induces gene expression of heat shock protein 70 and phosphorylation
      of mitogen activated protein kinases in the rat cerebellum.
AB  - In-vivo heat-shock induced heat shock factor (HSF) DNA-binding activity and
      accumulation of heat shock protein (hsp)70 mRNA in newborn and adult rat
      cerebellum was studied. We identified a high basal level of c-Jun N-terminal
      kinase (JNK) and p38 MAP kinase phosphorylation in the cerebellum, independently
      of age. Hyperthermia increased JNK1, decreased JNK2 but did not modify JNK3
      phosphorylation in the newborn cerebellum, whereas decreased the phosphorylation
      of both JNK1 and JNK3 in adult rats. During recovery from hyperthermia, JNK2
      phosphorylation returned to control level in the newborn, JNK1 appeared
      hyperphosphorylated only in the newborn, and JNK3 in all animals. JNK2 never
      appeared phosphorylated in the adult cerebellum. Hyperthermia increased p38 MAP
      kinase phosphorylation in the cerebellum, with different trends in newborn and
      adult rats during recovery. Heat shock increased extracellular signal-regulated
      kinase phosphorylation concomitant to tyrosine kinase receptor activation
      (epidermal growth factor-receptor in the newborn and insulin-like growth factor
      receptor in the adult cerebellum). The behavior of stress kinases may underlie a
      different age-related vulnerability to heat stress of the cerebellum.

PMID- 11595340
TI  - Lower excitability of the corticospinal tract to transcranial magnetic
      stimulation during lengthening contractions in human elbow flexors.
AB  - The purpose of this study was to characterize the neuromuscular control during
      shortening (SHO) and lengthening (LEN) contractions by investigating the input
      output (I/O) property in the corticospinal tract. To this end, the relation
      between various stimulus intensities applied via transcranial magnetic
      stimulation and the size of motor evoked potentials was investigated in six
      healthy subjects during elbow flexion and extension. The measured I/O property
      demonstrates a sigmoidal shape, and is characterized by a plateau value, maximum
      slope and threshold. The results demonstrated that both the plateau value and
      maximum slope were significantly lower during LEN contraction than during SHO
      contraction (P<0.05), whereas the threshold was found not to be significantly
      different. These results suggest that both the maximum excitation level and the
      gain of the corticospinal tract are reduced during LEN contractions.

PMID- 11595339
TI  - Baclofen attenuates harmaline induced tremors in rats.
AB  - Recent experimental and clinical studies clearly suggest the role of gamma
      aminobutyric acid (GABA) in the pathogenesis of tremors. The present study was
      undertaken to investigate the effect of baclofen, a GABA B receptor agonist on
      harmaline induced tremors. Four groups of female Wistar rats weighing 100+/-15 g
      were injected with harmaline (10 mg/kg, intraperitoneally) for inducing
      experimental tremors. The animals in groups 2, 3 and 4 were given baclofen by
      gavage at doses of 2.5, 5 and 10 mg/kg, respectively, half an hour before
      harmaline administration, whereas, the rats in group 1 served as control and
      received water. The latency of onset, intensity and duration of tremor and
      electromyographic (EMG) responses were recorded. Treatment with baclofen resulted
      in a dose dependent decrease in the intensity of tremor. Our EMG study also
      revealed a significant decrease in the amplitude of tremors in baclofen treated
      rats. A highly significant increase in latency of onset of tremor was observed in
      the rats treated with high dose (10 mg/kg) of baclofen only. This study clearly
      suggests beneficial effects of baclofen in harmaline induced tremors.

PMID- 11595341
TI  - Substance P and enkephalin containing fibers in the developing nucleus dorsalis
      of the human spinal cord.
AB  - A peroxidase-antiperoxidase immunostaining method was employed to determine the
      initial stage of appearance and localization of substance P (SP) and enkephalin
      (ENK) in the nucleus dorsalis of the developing human spinal cord. Both SP- and
      ENK-positive fibers started to appear from the 10th week of gestation in regions
      surrounding the nucleus dorsalis. SP-positive fibers then reached the nucleus at
      13 weeks and from 26 weeks to term, three strands of SP-positive fibers, which
      were predominantly originated from the superficial layers of the dorsal horn,
      penetrated into the nucleus dorsalis from its medial, median and lateral aspects.
      From 26 weeks onwards, ENK-positive fibers, originated from the superficial and
      the adjacent layers of the spinal cord, formed a thicker medial and a thinner
      lateral bundle projecting into the nucleus dorsalis. Our results show that both
      SP- and ENK-positive fibers started to appear at around 10 weeks and a consistent
      pattern of immunoreactivity was established by around 26-30 weeks of gestation.

PMID- 11595342
TI  - Pentobarbital and brilliant green modulate the current response of recombinant
      rat kainate-type GluR6 receptor channels differentially.
AB  - Kainate-type receptor channels (GluR5-7, KA1,2) belong to the family of
      ionotropic glutamate receptor channels. In the present study we tested the
      interaction of two different drugs with GluR6 channels using outside-out patches
      from HEK cells transiently transfected with cDNA of GluR6 channels. Glutamate and
      the respective drugs were delivered by a system for ultrafast solution exchange.
      Application of a saturating concentration of 3 mM glutamate resulted in fast
      current transients with desensitization time constants between 3 and 10 ms.
      Addition of pentobarbital (>or=1 mM) to the 3 mM glutamate containing test
      solution resulted in a significant decrease of the time constant of current decay
      without affecting the peak current amplitude. Brilliant green (>or=1 mM) had the
      opposite effect and led to an increase of the time constant of current decay
      after application of 3 mM glutamate. The pharmacological effects of both drugs
      were completely reversible. Additionally, a significant increase of the peak
      current amplitude and the time constant of deactivation in presence of brilliant
      green was observed. Summarizing our results, we could identify a further
      substance, brilliant green, interacting with GluR6 kainate-type receptor
      channels.

PMID- 11595343
TI  - Preservation of neurotrophin expression in microglia that migrate into the
      gerbil's brain across the blood-brain barrier.
AB  - Microglia isolated from a mixed glial culture drawn from neonatal Mongolian
      gerbils were demonstrated to produce high amounts of brain-derived neurotrophic
      factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). The gerbil
      microglia retained the capability to migrate into the brain parenchyma after
      intra-arterial injection. We found that exogenously migrated microglia retained
      their BDNF and GDNF productive ability and expressed large amounts of BDNF and
      GDNF in damaged brain areas which suggests microglia's role as a protectant of
      damaged neurons. Since peripherally injected microglia exhibit specific affinity
      for areas of neural damage within the brain, we suggest that microglia are
      possible tools for cell therapy of brain damage.

PMID- 11595344
TI  - Repetitive training of a synchronised movement induces short-term plastic changes
      in the human primary somatosensory cortex.
AB  - The aim of our study was to assess possible short-term plastic changes in the
      human primary somatosensory cortex (S1) induced by a repetitive synchronised
      movement of the right thumb and shoulder. We therefore performed a source
      localisation of somatosensory evoked potentials after median nerve stimulation in
      twelve healthy subjects before and after 1 h of motor training. We found a
      significant medial shift of the N20 dipole on the left hemisphere after training,
      whereas the dipole location on the right hemisphere remained unchanged. However,
      no significant correlation was seen between the dipole shift and the improvement
      in motor performance. We conclude that repetitive synchronised movements are able
      to induce plastic changes in the contralateral S1, which might be mainly due to
      the synchronised proprioceptive input.

PMID- 11595345
TI  - CMX-8933, a peptide fragment of the glycoprotein ependymin, promotes activation
      of AP-1 transcription factor in mouse neuroblastoma and rat cortical cell
      cultures.
AB  - An 8-amino acid peptide fragment (CMX-8933) of Ependymin, a glycoprotein
      component of the extracellular fluid and cerebrospinal fluid of goldfish brain,
      was synthesized and tested for its capacity to activate AP-1 transcription factor
      in cell cultures. Dose-response and time-course studies of AP-1's binding to DNA
      were carried out in neuroblastoma (NB2a/dl) and primary rat brain cortical
      cultures using an electrophoretic mobility shift assay (EMSA). A 13-14-fold
      increase in AP-1's DNA binding was obtained when NB2a cells were incubated for 4
      h with 6-10 microg/ml CMX-8933. Primary rat brain cortical cultures were much
      more sensitive to the effects of CMX-8933 than transformed (NB2a) cultures; here
      a 26.7+/-5.2-fold increase in binding was observed following a 3-h treatment with
      as little as 10 ng/ml peptide. These findings are consistent with an activation
      of this transcription factor, a characteristic that has been previously
      correlated with functional aspects of full-sized neurotrophic factors (nerve
      growth factor and brain-derived nerve growth factor) in neuronal differentiation
      and regeneration. Such data suggest a role for Ependymin in transcriptional
      control.

PMID- 11595346
TI  - Functional characterization of the splicing variants of human norepinephrine
      transporter.
AB  - Human norepinephrine transporter (NET) displays three splicing variants having
      different carboxy terminals, hNET, hNET C-t var1 and hNET C-t var2. Functional
      characterization of these isoforms was performed with transient expression system
      in COS-7 cells. Cells transfected with hNET C-t var2, but not hNET C-t var1,
      revealed a significant increase in [(3)H]norepinephrine (NE) uptake and
      [(3)H]nisoxetine binding as well as hNET, in association with their different
      cellular localization indicated by immunostaining using NET-specific antisera.
      Kinetic and pharmacological analyses of [(3)H]NE uptake revealed different
      characteristics between hNET and hNET C-t var2. These results suggest that hNET C
      t var2 may participate in NE transport in a manner different from hNET at
      noradrenergic synapses or in other tissues including placenta where NET variants
      were found to exist.

PMID- 11595347
TI  - Lithium-pilocarpine-induced status epilepticus in immature rats result in long
      term deficits in spatial learning and hippocampal cell loss.
AB  - Rat pups age of 14 postnatal day (P14) were subjected to lithium-pilocarpine (Li
      PC) model of status epilepticus (SE). Control rats (n=6) were given an equivalent
      volume of saline intraperitoneally. Behavioral testing began on P60 including the
      Morris water maze, the radial arm maze, and the rotarod test. Brain were then
      analyzed with cresyl violet stain for histological lesions and evaluated for
      mossy fiber sprouting with the Timm stain. We observed spatial memory deficits
      both in the Morris water maze and radial arm maze in Li-PC-treated rat. There was
      no motor impairment in Li-PC-treated rat by the rotarod test. Two of six Li-PC
      treated rats showed cell loss in hippocampal CA1 subfield. The Timm staining
      pattern was similar in both control and Li-PC-treated rats. Result of this study
      suggests that Li-PC-induced SE in immature rats cause long-term cognitive deficit
      and permanent cell loss in hippocampal CA1, but spare motor impairment.

PMID- 11595348
TI  - Effect of ApoE and tau on age of onset of progressive supranuclear palsy and
      multiple system atrophy.
AB  - In addition to allelic association between genetic polymorphisms and diseases,
      modulation of age of onset is a well recognised effect of disease susceptibility
      genes. The ApoE epsilon4 allele is associated with an earlier age of onset of
      sporadic and familial Alzheimer's disease. It has been suggested that the tau
      genotype influences the age of onset of progressive supranuclear palsy (PSP), a
      form of atypical parkinsonism caused by tau neurofibrillary tangle deposition. We
      have therefore analysed the relationship between tau and ApoE genotypes and the
      age of onset of PSP and another form of atypical parkinsonism, multiple system
      atrophy (MSA). We have not found any effect of possession of the tau H1 haplotype
      or the ApoE epsilon4 allele on the age of onset of MSA or PSP.

PMID- 11595351
TI  - Changing views of brain evolution.
AB  - Although brain studies began in ancient Egypt, speculations on vertebrate brain
      evolution occurred only much later, after the publication of Darwin's Origin of
      Species in 1859. Subsequently, views of brain evolution have been shaped by a
      complex interplay of theory and technique. Darwin's theory allowed the variation
      in brain size and complexity to be re-interpreted within an evolutionary context,
      albeit an erroneous pre-Darwinian context based on scala naturae. With the
      development of histological techniques, research shifted to descriptions of
      cellular structure, cellular aggregates and their putative interconnections. In
      spite of these technical advances, brain evolution continued to be viewed within
      the context of scala naturae. Following the publication of The Comparative
      Anatomy of the Nervous System of Vertebrates by Ariens Kappers, Huber, and Crosby
      in 1936, there followed a period of stasis, after which biological views of
      evolution were radically altered by the confluence of genetics, paleontology, and
      systematics, termed the Evolutionary Synthesis. Against this background, the
      development of new experimental techniques for establishing neural connections
      resulted in a new flowering of comparative neuroanatomy. While comparative
      descriptive and experimental studies of brain organization continue, the
      rapprochement of embryology and genetics is fueling a new renaissance that
      promises to increase our understanding of brain evolution and its genetic basis.

PMID- 11595349
TI  - An anxiolytic agent, dihydrohonokiol-B, inhibits ammonia-induced increases in the
      intracellular Cl(-) of cultured rat hippocampal neurons via GABA(c) receptors.
AB  - The effects of an anxiolytic honokiol derivative, dihydrohonokiol-B (DHH-B) [3'
      (2-propenyl)-5-propyl-(1,1'-biphenyl)-2,4'-diaol], on ammonia-induced increases
      in the intracellular Cl(-) concentration ([Cl(-)](i)) were examined using primary
      cultured rat hippocampal neurons. DHH-B (1-100 ng/ml), but not an inactive isomer
      of honokiol, magnolol (100 ng/ml), dose-dependently inhibited the ammonia-induced
      increases in [Cl(-)](i) without any changes in the control [Cl(-)](i). Such an
      effect of DHH-B was blocked by a gamma-aminobutylic acid A (GABA(A)) and GABA(C)
      Cl(-) channel blocker, 100 microM picrotoxin, and a GABA(C) receptor blocker, 10
      microM (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid, but not by a
      GABA(A) receptor blocker, 10 microM bicuculline. Further, a GABA(C) receptor
      agonist, 200 microM cis-4-aminocrotonic acid, but not a GABA(A) receptor agonist,
      10 microM muscimol, mimicked the effect of DHH-B. Thus, DHH-B appears to protect
      neurons from the ammonia-induced increases in [Cl(-)](i) through GABA(C) receptor
      stimulation.

PMID- 11595352
TI  - Common developmental genetic mechanisms for patterning invertebrate and
      vertebrate brains.
AB  - Recent genetic studies on embryonic brain development in the fly Drosophila
      melanogaster together with investigations on early morphogenesis and patterning
      in the embryonic brain of the mouse revealed developmental mechanisms that are
      strikingly similar in insects and mammals. The homeotic (Hox) genes are expressed
      in a virtually colinear anteroposterior pattern in the developing posterior brain
      of insects and mammals, where they are required for the specification of
      segmental neuronal identity. The otd/Otx cephalic gap genes are expressed in the
      anterior brain of insects and mammals and are of central importance for its
      formation because in both phyla loss of otd/Otx2 causes the loss of the entire
      rostral brain. Specific Pax genes are involved in numerous aspects of brain
      development in both phyla. These developmental genetic findings reveal a striking
      evolutionary conservation of cephalic gap gene, homeotic gene, and Pax gene
      action in embryonic brain development that extends beyond gene structure to
      encompass patterned expression and function. This comparative evidence indicates
      that the genetic programs which direct embryonic brain development are remarkably
      conserved and lends further support to the hypothesis that a common molecular
      bauplan underlies brain development in invertebrates and vertebrates. In
      consequence, it seems increasingly likely that both modern brain types share
      their evolutionary origin in a common ancestral bilaterian brain which was
      established before the protostome-deuterostome divergence over 600 million years
      ago.

PMID- 11595353
TI  - Correlated patterns of neuron differentiation and Hox gene expression in the
      hindbrain: a comparative analysis.
AB  - Hindbrain neurons are organized into coherent subpopulations with characteristic
      projection patterns and functions. Many of these serve vital functions that have
      been conserved throughout the vertebrate radiation, but diversification to
      modified or highly specialized functions has also occurred. The differentiation
      of identifiable neuron groups in specific spatial domains must involve the
      regional expression of determinants within the hindbrain neuroepithelium. The Hox
      genes are involved in longitudinal regionalization of the neural tube, and their
      expression patterns in the hindbrain are closely related to the rhombomeres which
      partition the hindbrain into morphogenetic units. Hox gene expression also
      exhibits conserved patterning as well as phylogenetic variation. One plausible
      mechanism that may have contributed to evolutionary diversification in hindbrain
      neuron populations is therefore the emergence of species-specific differences in
      Hox gene expression. This article presents a comparative overview of the regional
      patterning of selected Hox genes and hindbrain neuron populations in several
      embryologically important species. Although tantalizing correlations exist, the
      relationship between Hox genes and neuronal patterning is complex, and
      complicated by dynamic features in each. Much more comparative and developmental
      data must be obtained before the link between Hox gene expression and hindbrain
      neuron patterning can be elucidated satisfactorily in an evolutionary context.

PMID- 11595354
TI  - Brain segmentation and forebrain development in amniotes.
AB  - This essay contains a general introduction to the segmental paradigm postulated
      for interpreting morphologically cellular and molecular data on the developing
      forebrain of vertebrates. The introduction examines the nature of the problem,
      indicating the role of topological analysis in conjunction with analysis of
      various developmental cell processes in the developing brain. Another section
      explains how morphological analysis in essence depends on assumptions
      (paradigms), which should be reasonable and well founded in other research, but
      must remain tentative until time reveals their necessary status as facts for
      evolving theories (or leads to their substitution by alternative assumptions).
      The chosen paradigm affects many aspects of the analysis, including the
      sectioning planes one wants to use and the meaning of what one sees in brain
      sections. Dorsoventral patterning is presented as the fundament for defining what
      is longitudinal, whereas less well-understood anteroposterior patterning results
      from transversal regionalization. The concept of neural segmentation is covered,
      first historically, and then step by step, explaining the prosomeric model in
      basic detail, stopping at the diencephalon, the extratelencephalic secondary
      prosencephalon, and the telencephalon. A new pallial model for telencephalic
      development and evolution is presented as well, updating the proposed homologies
      between the sauropsidian and mammalian telencephalon.

PMID- 11595355
TI  - Evolution and development of the vertebrate ear.
AB  - This review outlines major aspects of development and evolution of the ear,
      specifically addressing issues of cell fate commitment and the emerging molecular
      governance of these decisions. Available data support the notion of homology of
      subsets of mechanosensors across phyla (proprioreceptive mechanosensory neurons
      in insects, hair cells in vertebrates). It is argued that this conservation is
      primarily related to the specific transducing environment needed to achieve
      mechanosensation. Achieving this requires highly conserved transcription factors
      that regulate the expression of the relevant structural genes for mechanosensory
      transduction. While conserved at the level of some cell fate assignment genes
      (atonal and its mammalian homologue), the ear has also radically reorganized its
      development by implementing genes used for cell fate assignment in other parts of
      the developing nervous systems (e.g., neurogenin 1) and by evolving novel sets of
      genes specifically associated with the novel formation of sensory neurons that
      contact hair cells (neurotrophins and their receptors). Numerous genes have been
      identified that regulate morphogenesis, but there is only one common feature that
      emerges at the moment: the ear appears to have co-opted genes from a large
      variety of other parts of the developing body (forebrain, limbs, kidneys) and
      establishes, in combination with existing transcription factors, an environment
      in which those genes govern novel, ear-related morphogenetic aspects. The ear
      thus represents a unique mix of highly conserved developmental elements combined
      with co-opted and newly evolved developmental elements.

PMID- 11595356
TI  - Evolution of vertebrate neuropeptides.
AB  - This review describes some of the most typical features in the evolution of
      neuropeptides. Neuropeptides are synthesized like other polypeptides and
      proteins, with an amino acid sequence determined by the DNA sequence of the
      corresponding gene. Mutations of bases in the coding regions of the DNA lead to
      changes in amino acid sequence, and explain the differences in amino acid
      sequence of a certain neuropeptide in different animal species. The more
      distantly related two species are, the more substitutions can be found in one and
      the same neuropeptide. The biologically active part of the neuropeptide is
      usually the most conserved part. Neuropeptides also form families of closely
      related peptides, where several members may occur in one animal species. This is
      due to gene or exon duplications followed by mutations. Gene splicing and
      posttranslational processing decides the gene product in a single cell.
      Difference in sequence may cause difference in function, but more often than not,
      members of a family appear to produce the same effect. Three neuropeptide
      families, the tachykinins, the neuropeptide Y family, and the vasoactive
      intestinal polypeptide/pituitary adenylate cyclase-activating peptide family will
      be described in more detail.

PMID- 11595357
TI  - Alterations of medial preoptic area neurons following pregnancy and pregnancy
      like steroidal treatment in the rat.
AB  - There is a marked increase in the maternal behavior displayed by a female rat
      following pregnancy-due primarily to exposure to the gonadal hormones
      progesterone and estradiol (P and E(2), respectively). We examined Golgi-Cox
      silver-stained, Vibratome-sectioned neurons visualized and traced using
      computerized microscopy and image analysis. In Part One, we examined the hormonal
      neural concomitants in the medial preoptic area (mPOA), an area of the brain that
      regulates maternal behavior, by comparing cell body size (area in microm(2); also
      referred to as soma and perikaryon) in the mPOA and cortex of five groups (n = 4
      6/group) of ovariectomized (OVX-minus), diestrous, sequential P and E(2)-treated
      (P+E(2)), late-pregnant, and lactating rats; for Part Two, we examined a subset
      of mPOA neurons, which were traced in their entirety, from these same subjects.
      In Part One, whereas there was no difference between OVX-minus and diestrous
      females, both had smaller somal areas compared to OVX+P+E(2)-treated and late
      pregnant females. The area of the soma returned to diestrous/OVX-minus levels in
      the lactating females. We found no change among the five groups in area of cell
      body in cortical neurons, which generally lack steroid receptors. In Part Two,
      which included a more detailed morphometric analysis of mPOA neurons, we examined
      several additional measures of dendritic structure, including number of proximal
      dendritic branches (the largest proximal dendrite was defined as the one with the
      largest diameter leaving the soma); cumulative length of the largest proximal
      dendrite; area of the cell body; number of basal dendrites; cumulative basal
      dendritic length; number of basal dendritic branches; and branch-point (distance
      from cell body to first branch of largest proximal dendrite). Again, we found
      similar effects on cell body size as in Part One, together with effects on number
      of basal dendritic branches and cumulative basal dendritic length in pregnant and
      P+E(2)-treated groups compared to OVX, diestrous, and lactating. An increase in
      somal area denotes increased cellular activity, and stimulatory effects on
      additional neuronal variables represents modifications in information processing
      capacity. Pregnancy and its attendant hormonal exposure, therefore, may stimulate
      neurons in the mPOA, which then contribute (in an as yet undetermined manner) to
      the display of maternal behavior. During the postpartum lactational period, when
      cues from pups primarily maintain maternal attention, the neuronal soma appears
      to return to a pre-pregnancy, non-hormonally dependent state, whereas other
      aspects of the dendrite remain altered. Collectively, these data demonstrate a
      striking plasticity in the brains of females that may be reflected in
      modifications in behavior.

PMID- 11595358
TI  - Effects of acute and chronic fluoxetine treatments on restraint stress-induced
      Fos expression.
AB  - Chronic treatment with antidepressants has been shown to attenuate behavioral
      changes induced by uncontrollable stress. The mechanisms and brain sites of this
      effect, however, remain controversial. The objective of the present work was to
      investigate the effects of chronic and acute treatment with fluoxetine (FLX), a
      selective serotonin reuptake blocker, on Fos expression in animals submitted to
      restraint stress. Male Wistar rats (n = 3-9/group) received, during 1 or 21 days,
      intraperitoneal. Injections of vehicle (saline + 0.2% Tween-80, 1 ml/kg) or FLX
      (10 mg/kg). One hour after the last injection they were forced restrained for 2 h
      and sacrificed immediately after. Non-stressed animals were sacrificed 2 h after
      the last injection. The brains were removed and processed for
      immunohistochemistry. Fos-like immunoreactivity (FLI) was quantified by a
      computer system. In acutely treated animals FLX decreased stress-induced FLI in
      the medial amygdala (MeA), bed nucleus of the stria terminalis (BNST),
      ventrolateral part, and dorsolateral periaqueductal gray (PAG). After chronic
      treatment, however, the drug induced a significant increase in FLI in the BNST
      (ventrolateral and medial parts), lateral septal nucleus (LSN, dorsal part),
      dorsal raphe nucleus (DRN), and locus coeruleus in restrained group. In non
      restrained animals chronic treatment with FLX increased FLI in the MeA, BNST
      (ventrolateral and dorsolateral parts), LSN (dorsal and intermediate parts),
      dorsolateral and dorsomedial PAG and in the DRN. The results suggest that chronic
      fluoxetine treatment induce plastic changes that result in a different regional
      pattern of Fos expression.

PMID- 11595359
TI  - The anxiolytic effect of acute ethanol or diazepam exposure is unaltered in mu
      opioid receptor knockout mice.
AB  - Previous researchers demonstrate an opioidergic involvement in the anxiolytic and
      rewarding actions of ethanol and diazepam. Therefore, to further characterize the
      role of the opioid system in the anxiolytic action of ethanol and diazepam,
      normal (C57BL/6J), hybrid (B6129F1) and mu-opioid receptor knockout mice were
      given i.p. ethanol (0, 1.0 or 1.6 g/kg) or diazepam (1.5 mg/kg). The anxiolytic
      properties of these agents were then tested in the elevated plus-maze. Additional
      ethanol-treated mu-opioid receptor knockout mice (1 g/kg) were pretreated with
      the kappa-opioid receptor antagonist nor-BNI (0 or 3 mg/kg) to assess the
      involvement of kappa-opioid activity in ethanol's anxiolytic actions. The
      anxiolytic action of ethanol and diazepam in the mu-opioid receptor knockout
      mouse did not differ from the effects obtained in normal mice and pretreatment
      with nor-BNI did not significantly attenuate ethanol's actions in mu-opioid
      receptor knockout mice. Thus, the anxiolytic actions of ethanol and diazepam
      appear to be independent of opioid system activity in the mu-opioid receptor
      knockout mouse.

PMID- 11595360
TI  - Rate-independent inhibition by norepinephrine of 5-HT release from the
      somadendritic region of serotonergic neurons.
AB  - Endogenous adrenergic drive regulates the firing rate of serotonergic neurons.
      However, advocates of feedback theory assert that 5-hydroxytryptamine (5-HT)
      released in the somatodendritic region of raphe neurons regulates both rate and
      release of 5-HT. Experiments were done to determine if the somatodendritic region
      might have receptors for norepinephrine that inhibit release of 5-HT
      independently of rate, as this would allow for discrete effects of norepinephrine
      on rate and release, even in the presence of functional feedback by 5-HT. The
      release of 5-HT at fixed frequencies of stimulation was substantially reduced
      when norepinephrine (1 and 3 x 10(-7) M) was present. Norepinephrine also
      inhibited the release of 3H-5-HT with delivery of a single stimulation pulse
      ruling out a remote action of the catecholamine. The alpha(1) antagonist prazosin
      did not modify the profile of norepinephrine inhibition. Further, the alpha(1)
      agonist phenylephrine had no effect on 3H-5-HT efflux. The alpha(2) antagonist
      yohimbine antagonized almost entirely the inhibition by norepinephrine at 1 Hz,
      and reduced it substantially at 3 Hz. Blockade of 5-HT(1) receptor sites with
      methiothepin did not reduce the inhibitory effect of norepinephrine on 3H-5-HT
      efflux. It is proposed that release of endogenous norepinephrine at synapses with
      5-HT neurons could activate 5-HT neuron firing rate through alpha(1) receptors
      located at the soma and simultaneously short-circuit ongoing 5-HT feedback
      inhibition by inhibiting release through adrenergic alpha two receptors likely
      located at the dendrites.

PMID- 11595361
TI  - Effect of neonatal treatment with monosodium glutamate on dopaminergic and L-DOPA
      ergic neurons of the medial basal hypothalamus and on prolactin and MSH secretion
      of rats.
AB  - The effect of neonatal treatment with monosodium L-glutamate (MSG) on the
      dopaminergic systems of the medial basal hypothalamus has been investigated using
      tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC)
      immunocytochemistry. Changes in plasma levels of prolactin (PRL) and alpha
      melanocyte-stimulating hormone (MSH) have also been determined in intact and in
      MSG-treated rats after inhibition of TH by alpha-methyl-p-tyrosine (alpha-MpT) or
      without inhibition of enzyme activity. Monosodium glutamate resulted in a 40%
      reduction in the number of TH immunopositive tuberoinfundibular neurons, but no
      change in the number of AADC-positive tuberoinfundibular nerve cells, indicating
      that this reduction has occurred mainly in TH-positive but AADC-negative
      elements, i.e., in L-DOPA-ergic neurons. In contrast, MSG did not cause changes
      in the number of TH and AADC immunoreactive neurons of the
      periventriculohypophysial and tuberohypophysial dopaminergic systems, and it did
      not influence basal plasma PRL levels. alpha-methyl-p-tyrosine has increased
      plasma PRL concentrations in both control and MSG-treated rats of both sexes, but
      significantly higher responses were detected in females. None of the treatments
      had any effect on plasma MSH level. These findings suggest that MSG affects
      primarily L-DOPA-ergic neurons located in the ventrolateral part of the arcuate
      nucleus, but not dopaminergic neurons situated in the dorsomedial part of the
      arcuate nucleus; neither PRL nor MSH secretion is altered by MSG; a significant
      sex difference exists in the pituitary PRL response to inhibition of TH, and this
      response is not affected by MSG.

PMID- 11595362
TI  - Mapping of brain activation in response to pharmacological agents using fMRI in
      the rat.
AB  - Functional MRI (fMRI) was used to investigate the effects of psychotropic
      compound activity in the rat brain in vivo. The effects of dizocilpine (MK-801)
      an N-methyl-D-aspartate receptor antagonist and m-chlorophenylpiperazine (mCPP),
      a 5-HT(2b/2c)-receptor agonist on rat brain activity were investigated over a
      time interval of about 1 h and the results were compared to published glucose
      utilisation and cerebral blood flow data. Signal magnitude increases were
      observed predominantly in limbic regions following MK-801 administration (0.5
      mg/kg i.v) whereas signal decreases were restricted to neocortical areas; a
      characteristic, time dependent pattern of regional changes evolved from the
      thalamic nuclei to cortical regions. In contrast, mCPP (25 mg/kg i.p) produced
      gradual signal intensity increases in limbic and motor regions with signal
      decreases restricted to the visual, parietal and motor cortices. The results from
      both compounds show remarkable similarity with autoradiographic measurements of
      cerebral blood flow and glucose uptake. These experiments suggest that the spatio
      temporal capabilities of fMRI may be applied to the in vivo investigation of
      psychoactive compound activity with potential for clinical applications.

PMID- 11595363
TI  - The measurement of fetal liver T(*)(2) in utero before and after maternal oxygen
      breathing: progress towards a non-invasive measurement of fetal oxygenation and
      placental function.
AB  - Utero-placental insufficiency is thought to be a major cause of growth
      retardation in utero and an important risk factor in the perinatal period. The
      purpose of this study was to investigate whether MRI could detect changes of
      fetal oxygenation, based on the blood oxygenation level dependence (BOLD) of the
      MRI tissue signal. Nine third trimester women (34-38 weeks) with normal
      pregnancies underwent abdominal MRI examinations. Following localization of the
      fetal liver using T(2)-weighted single-shot HASTE scans, up to 7 breath-held
      transaxial single-slice gradient-echo image sets were obtained through the fetal
      liver. The mother then commenced oxygen breathing with the imaging procedure
      repeated after 20 minutes of O(2) breathing. For each image set, T(*)(2) values
      are calculated using linear regression of log (signal) versus TE for a region of
      interest within the fetal liver selected by the attending radiologist. Fetal
      liver T(*)(2) values were calculated before and after O(2) breathing for each
      multi-echo image acquisition set. A signed rank test was used to test for a
      significant change in fetal liver T(*)(2) between the pre-O(2) and post-O(2)
      image sets. A significant increase in T*(2) (alpha < 0.05) was seen in 5 of the 9
      fetal livers, a smaller increase (of borderline statistical significance, alpha =
      0.057) in 2 livers, and no significant change (alpha > 0.05) in 2 livers. Our
      study indicates that T(*)(2) measurement of the fetal liver may detect alteration
      in fetal oxygen level following maternal oxygenation using the BOLD effect. This
      technique may potentially be applied to the identification and understanding of
      placental dysfunction in intra-uterine growth retardation.

PMID- 11595364
TI  - Gravity-dependent perfusion of the lung demonstrated with the FAIRER arterial
      spin tagging method.
AB  - Magnetic resonance imaging of lung perfusion using an arterial spin tagging (AST)
      sequence called flow sensitive alternating inversion recovery with an extra RF
      pulse (FAIRER) was performed in the left and right lateral positions in five
      volunteers. Coronal slices were obtained and the average intensity of each lung
      was measured. In both positions, an increase in the intensity of the dependent
      lung was found (229% for left lateral, 40% for right lateral). No change was seen
      along an isogravitational plane. Lung volumes were measured in each position to
      account for the compression of the lungs by the heart. This effect was found to
      be symmetric and did not contribute to the perfusion gradient. This demonstrates
      that AST is sensitive to gravity-dependent perfusion gradients in the lung.

PMID- 11595365
TI  - On the use of the FLAIR technique to improve the correction of eddy current
      induced artefacts in MR diffusion tensor imaging.
AB  - Eddy current induced geometric distortions can only be accurately corrected in
      brain diffusion-weighted echo-planar (DW-EP) images for b-values less than
      approximately 300 s mm(-2) using the iterative cross-correlation (ICC) algorithm.
      This is due to the difference in signal intensity of the cerebrospinal fluid
      (CSF) compartment in the diffusion-weighted and baseline T(2)-weighted echo
      planar (T2W-EP) images. At larger values of b, image misalignment artefacts can,
      however, be removed by directly correlating CSF-suppressed T2W-EP images with non
      CSF-suppressed and CSF-suppressed DW-EP images. Separate phantom experiments can
      also be performed to provide eddy current calibration data. Here the ability of
      these methods to remove eddy current induced artefacts from DW-EP images
      collected in volunteer diffusion tensor imaging (DTI) experiments is
      investigated. Monte Carlo simulations show that in order for the ICC algorithm to
      produce accurate estimates of the eddy current induced distortions at b-values
      greater than 1000 s mm(-2), the degree of CSF suppression should be greater than
      approximately 80%. This condition is typically met for FLAIR inversion times
      between 0.5 and 0.8 of the spin-lattice relaxation time of CSF. In volunteer
      studies the most complete image realignment was provided by direct correlation of
      CSF-suppressed T2W-EP and DW-EP images acquired in the FLAIR DTI experiment.
      These results indicate that although calibration data obtained from brain or
      phantom images can significantly reduce eddy current induced distortions, the
      optimum image realignment achievable using post-processing methods is likely to
      be that obtained by direct image warping techniques.

PMID- 11595366
TI  - Optimization of view ordering for motion artifact suppression.
AB  - Motion artifacts in MRI may be reduced by optimized view ordering. Extensive
      simulations of view-ordering techniques were performed on high-resolution phantom
      images to determine the best strategy for distributing motion in k-space.
      Although not exhaustive, simulation results indicate that minimizing motion at
      the center of k-space is critical to overall image quality. For 2D imaging, using
      edge-center-edge view order and setting the readout direction parallel to the
      direction of the motion produces the sharpest point spread function and the
      lowest image energy error. For 3D imaging, using an edge-center-edge view order
      proves to be the optimum choice in general. Given these observations, several
      important issues regarding the measurement of motion effects are discussed.

PMID- 11595367
TI  - A quantitative comparison of motion detection algorithms in fMRI.
AB  - An important step in the analysis of fMRI time-series data is to detect, and as
      much as possible, correct for subject motion during the course of the scanning
      session. Several public domain algorithms are currently available for motion
      detection in fMRI. This paper compares the performance of four commonly used
      programs: AIR 3.08, SPM99, AFNI98, and the pyramid method of Thevenaz, Ruttimann,
      and Unser (TRU). The comparison is based on the performance of the algorithms in
      correcting a range of simulated known motions in the presence of various degrees
      of noise. SPM99 provided the most accurate motion detection amongst the
      algorithms studied. AFNI98 provided only slightly less accurate results than
      SPM99, however, it was several times faster than the other programs. This
      algorithm represents a good compromise between speed and accuracy. AFNI98 was
      also the most robust program in presence of noise. It yielded reasonable results
      for very low signal to noise levels. For small initial misalignments, TRU's
      performance was similar to SPM99 and AFNI98. However, its accuracy diminished
      rapidly for larger misalignments. AIR was found to be the least accurate program
      studied.

PMID- 11595368
TI  - Magnetic resonance imaging of simple and infected hydatid cysts of the brain.
AB  - Hydatid cyst of the brain is more common in children than adults. The cyst is
      always solitary unless the primary site is the brain. Cerebral hydatid cyst
      (CHCy) is most frequently supratentorial involving the territory of the middle
      cerebral artery, especially the parietal lobe. This study included 16 patients
      who were treated for CHCy. They were 11 male patients (68.75%), and 5 female
      patients (31.25%), ranging in age from 6 to 40 years with an average age of 14.7
      years. Most of the patients were children-12 patients (75%), between 6 to 16
      years of age. All patients were from rural areas. Headache, vomiting and seizures
      were the predominant symptoms. Papilloedema was present in 12 patients (75%). CT
      and MRI were performed in all patients. The cysts were all located in the
      cerebral hemispheres, except one in the posterior fossa, (Rt. cerebellar
      hemisphere). One lobe alone was affected in 7 patients (43.8%), two lobes in 6
      patients (37.5%) and 3 lobes in two patients (12.5%). Round, or oval well defined
      cystic lesions isointense to the CSF in T1 and T2WI, with hypointense walls in
      T2WI and no surrounding perifocal edema or evidence of contrast enhancement were
      seen in 12 patients (75%) and were classified as simple or non-complicated CHCy.
      Cystic lesions with surrounding, T2 hyperintense area of perifocal edema,
      complete and incomplete (segment) rim of contrast enhancement were seen in 4
      patients (25%), and were labeled as complicated or infected cysts (cysts with
      superadded pyogenic infection). All patients were treated surgically, hydatid
      birth (delivery of unruptured cyst) was achieved in 10 patients, cyst rupture
      occurred in 6 patients (37.5%), with subsequent recurrence (3 patients with
      recurrent multiple cysts and 3 patients with recurrent solitary cysts). All the
      recurrent cysts were surrounded by perifocal edema and showed ring enhancement.
      MRI has proved to be an excellent means of studying CHCy. It will be more widely
      used for diagnosis and surgical planning. It provided information about the exact
      cyst localization, cyst contents and presence or absence of superadded cyst
      infection.

PMID- 11595369
TI  - Low field thoracic MRI--a fast and radiation free routine imaging modality in
      children.
AB  - Radiography of the chest is the most frequently performed radiological
      examination in pediatric imaging. However, it is associated with the application
      of ionizing radiation. In order to avoid ionizing radiation in children a new and
      very fast MRI technique has been developed at our center as an alternative to the
      pediatric chest X-ray. 100 patients who had received a chest X-ray were
      additionally investigated in a 0.2 T low-field MR-scanner by a modified true FISP
      sequence with an acquisition time of 3.6-4.6 s for a coronal triple-slice scan. X
      ray and MR images were independently evaluated and later compared by two
      pediatric radiologists. Total investigation times (door-to-door time) for X-ray
      and MRI were comparable. The signal-to-noise ratio for lung parenchyma was 4.6
      7.3. Of 189 pathologic findings 165 were depicted on MR images as well as
      radiographs, 18 were noted on MRIs only, 6 on X-rays only. Overall kappa was
      0.87. True FISP MRI may be a good alternative to conventional chest X-ray. The
      main advantages are: fast imaging free of ionizing radiation, easy performance,
      no need for special equipment, optional imaging in all 3 planes, good image
      quality, and a high diagnostic value.

PMID- 11595370
TI  - Initial changes of non-traumatic osteonecrosis of femoral head in fat suppression
      images: bone marrow edema was not found before the appearance of band patterns.
AB  - The present study examined initial changes in non-traumatic osteonecrosis of the
      femoral head (ONF) on T1- and T2-weighted MR images, and fat suppression images.
      The subjects were 57 renal transplant recipients (37 males and 20 females), whose
      median age at the time of transplantation was 31.5 years old (range, 10 to 58
      years). Twelve patients developed band patterns (sign of established ONF) at an
      early postoperative period. Among them, 4 joints of 3 patients had a localized,
      faint signal abnormality in fat suppression images, where band pattern was
      confirmed later in T1- and T2-weighted images. In all the 57 patients, no bone
      marrow edema preceding to ONF was observed. Bone marrow edema would not be the
      cause of ONF in renal transplant patients. Early changes depicted in our fat
      suppression images would be useful information in the studies on pathogenesis of
      ONF.

PMID- 11595371
TI  - Post mortem energy metabolism and pH development in porcine M. longissimus dorsi
      as affected by two different cooling regimes. A (31)P-NMR spectroscopic study.
AB  - (31)P-NMR spectroscopy was carried out on M. longissimus dorsi samples chilled by
      two different cooling profiles corresponding to commercial batch and tunnel
      chilling. The half-life of post mortem phosphocreatine (PCr) degradation was
      found to be significantly less in muscle samples exposed to tunnel chilling
      (rapid) compared with muscle samples exposed to batch chilling (soft) conditions,
      while no difference in the post mortem ATP degradation was found. Moreover, the
      post mortem pH development in the muscle samples differed considerably between
      the two cooling regimes. A maximum difference of approx. 0.25 pH units between
      the two cooling profiles was observed around 150 min post mortem. Theoretical
      calculations of the registered pH difference between rapid and soft chilling of
      muscle samples revealed that the temperature effect on the buffer capacity of
      muscle is the major determining factor in the detected difference in
      intracellular pH between the two cooling profiles, while any contribution from a
      temperature-induced delayed progress in the lactate formation post mortem seems
      negligible. Moreover, calculations on the effect of the registered pH difference
      between rapid and soft chilling of muscle samples resemble a 2.5 times greater
      denaturation of myosin in samples which were chilled softly compared with samples
      chilled more rapidly. Finally, the relationship to the functionality of meats
      from soft and rapid chilled pork carcasses is discussed.

PMID- 11595372
TI  - Multi-channel magnetic resonance spectroscopy through time domain multiplexing.
AB  - Time domain multiplexing (TDM) is presented as a viable approach to increasing
      the sensitivity and efficiency of magnetic resonance spectroscopic (MRS)
      experiments through multi-channel signal acquisition. By switching very rapidly
      between coils of a receive phased array, TDM receiver extensions allow the
      acquisition of multiple, independent spectra through a single channel magnetic
      resonance console. A TDM receiver extension designed for imaging and spectroscopy
      is described, and the impact of this hardware extension on the processing and
      quantitation of MRS data is addressed. The primary complication involves the use
      of fixed bandwidth RF band-pass filters that can not be adjusted to match the
      spectral width of the desired MRS experiment.MRS sequences whose bandwidths are
      narrower than the bandwidth provided by TDM band-pass filters can be acquired
      through TDM with minimal loss of SNR as long as two constraints are met. The
      first constraint requires that the entire bandwidth of the band-pass filters be
      sampled at or more rapidly than the Nyquist rate associated with their bandwidth,
      to prevent extra noise from aliasing into the final spectrum. The second
      requirement is that spectral resolution be held constant to that of the desired
      experiment. Results from a two-channel multiplexed MRS experiment, conducted
      according to these guidelines, illustrate that TDM can be used to allow
      acquisition of multi-channel MRS experiments through single channel console
      systems with a minimal loss in SNR.

PMID- 11595373
TI  - A sixteen-channel multiplexing upgrade for single channel receivers.
AB  - With the increasing interest in phased arrays in magnetic resonance imaging,
      imaging system receivers capable of acquiring larger number of parallel signals
      are needed. Suggested techniques for rapid imaging propose the use of arrays with
      as many as 128 elements. While simply duplicating the number of receiver chains
      as needed is a viable technique, it quickly becomes both cumbersome and
      expensive. Time domain multiplexing offers an alternative solution to this
      problem. By using RF multiplexing switches, a single receiver can be upgraded to
      an array receiver capable of multi-channel data acquisition giving users array
      capability. Additionally, it can be used to dramatically increase acquisition
      capability of multiple receiver systems. This paper reports results from a
      multiplexing system upgrade, which converts a single channel standard clinical
      imaging system to a 16-channel array system. The upgrade includes both the RF
      multiplexing front-end and an external data acquisition system with image
      processing capability. Issues concerning the implementation of high channel-count
      multiplexers are also discussed.

PMID- 11595374
TI  - An exact form for the magnetic field density of states for a dipole.
AB  - We present an analytical form for the density of states for a magnetic dipole in
      the center of a spherical voxel. This analytic form is then used to evaluate the
      signal decay as a function of echo time for different volume fractions and
      susceptibilities. The decay can be considered exponential only in a limited
      interval of time. Otherwise, it has a quadratic dependence on time for short echo
      times and an oscillatory decaying behavior for long echo times.

PMID- 11595375
TI  - Kinetic evaluation of an i.v. bolus of MR contrast media.
AB  - Currently, it is assumed that the pharmacokinetic properties of the first minutes
      of an I.V. MR contrast media bolus are similar to those of an i.v. iodinated
      contrast media bolus used in CT. Correct timing of an MRA examination is crucial
      for obtaining sufficient arterial contrast. This study sought to evaluate the
      temporal change of arterial signal intensity within 150 s after i.v. bolus
      injection of Gd-DTPA. Thirty consecutive patients (14 women/16 men; mean age: 51
      +/- 11 years) were prospectively examined with a 1.0 Tesla clinical scanner. A
      single axial slice was acquired in 1.25 sec with manufacturer provided gradient
      echo sequence through the aorta at the level of the renal arteries. Investigation
      was started simultaneously to the application of contrast media (0.1 mmol/kg
      bodyweight Gd-DTPA at three different rates 2 mL/sec, 3 mL/sec and 4 mL/sec) and
      repeated for 2.5 min. An additional echo Doppler examination excluded patients
      with any cardiac disorders. Maximum signal (1300% increase compared to the basic
      value) in the aorta was achieved 20 +/- 6 sec after start of bolus injection.
      Then a plateau phase was maintained for the remaining investigation time (2.5
      min). No significant difference was shown for different injection rates. After a
      bolus injection of Gd-DTPA the arterial contrast remains on a high level for at
      least 2 min. However, correct timing of the bolus arrival is still crucial to
      discriminate arteries and veins. An injection rate between 2 mL/sec and 4 mL/sec
      has no influence on early contrast media dynamics.

PMID- 11595376
TI  - A device for feline head positioning and stabilization during magnetic resonance
      imaging.
AB  - Minimization of head movement and reproduction of standard head positions are
      essential for reliable brain functional magnetic resonance imaging. Devices for
      stabilization and alignment of feline preparations are not available currently.
      We describe a system that involves minimal surgery, allows for both acute and
      chronic atraumatic positioning, and has the potential to be used for
      unanesthetized animals. The device uses non-metallic materials and stabilizes the
      head by means of an apparatus that fixes the head with nylon screws and dental
      cement in the frontal sinuses. Application of the head-stabilizing device
      decreases head movements by more than a factor of ten. Anatomical images show
      that this device provides 3 dimensional head placement at a precision comparable
      to that of a stereotactic frame, i.e. within 1 mm.

PMID- 11595377
TI  - Elimination of k-space spikes in fMRI data.
AB  - The subtle signal changes in functional magnetic resonance imaging (fMRI) can be
      easily overwhelmed by noise of various origins. Spikes in the collected fMRI raw
      data often arise from high-duty usage of the scanner hardware and can introduce
      significant noise in the image and thereby in the image time series.
      Consequently, the spikes will corrupt the functional data and degrade the result
      of functional mapping. In this work, a simple method based on processing the time
      course of the k-space data are introduced and implemented to remove the spikes in
      the acquired data. Application of the method to experimental data shows that the
      methods are robust and effective for eliminating of spike-related noise in fMRI
      time series.

PMID- 11595379
TI  - cRel induces mitochondrial alterations in correlation with proliferation arrest.
AB  - We have previously shown that overexpressing cRel, a transcription factor of the
      Rel/NF-kappa B family, concomitantly inhibits proliferation of HeLa cells and
      makes them resistant against TNF alpha-induced apoptosis. Both effects rely on
      the upregulation of the manganese superoxide dismutase (MnSOD), a mitochondrial
      enzyme that converts O(2)(*-) in H(2)O(2). Here we describe additional
      alterations induced by cRel, namely mitochondrial clustering and accumulation of
      dense dark granules near the nucleus. These changes preferentially occur in cells
      that display a sustained cRel expression in the nucleus and that are cell-cycle
      arrested. As the cell-cycle arrest, these changes are reproduced by directly
      overexpressing MnSOD or by treating cells with H(2)O(2), suggesting they are due
      to MnSOD induction and ensuing H(2)O(2) accumulation. We propose that
      mitochondria cluster because they are damaged by the H(2)O(2) they overproduce.
      They would then be autophagocytosed and degraded in secondary lysosomes. In
      support of this scenario, we documented the occurrence of oxidative damage and
      the presence of lysosomes in the area of mitochondrial clustering. In addition,
      we identified the dense dark granules as lipofuscin, based on their
      autofluorescence. Lipofuscin could directly originate from the mitochondrial
      degradation products that would aggregate and become indigestible because of the
      presence of H(2)O(2) in the secondary lysosomes. Altogether, our findings show
      that cRel overexpression in HeLa cells creates, via the induction of MnSOD, an
      oxidative injury that culminates in mitochondrial degeneration, proliferation
      blockage, and resistance against TNF alpha-induced apoptosis.

PMID- 11595378
TI  - Oxidative stress and eicosanoids in the kidneys of hyperglycemic rats treated
      with dehydroepiandrosterone.
AB  - Oxidative stress plays a crucial role in the pathogenesis of chronic diabetic
      complications. Normoglycemic and streptozotocin-diabetic rats were treated with
      dehydroepiandrosterone (DHEA) (4 mg/d per rat) for 3 weeks. At the end of
      treatment, hydroxynonenal, hydroperoxyeicosatetraenoic acids and antioxidant
      levels, as well as Na/K-ATPase activity and membrane fatty acids composition were
      evaluated in kidney homogenates. Chronic hyperglycemia caused a marked increase
      of both hydroxynonenal and lipoxygenase pathway products and a drop in both GSH
      levels and membrane Na/K-ATPase activity. DHEA treatment restored the antioxidant
      levels to close to the control value and considerably reduced hydroxynonenal and
      hydroperoxyeicosatetraenoic acid levels. Moreover, DHEA counteracted the
      detrimental effect of hyperglycemia on membrane function: the drop of Na/K-ATPase
      activity in diabetic animals was significantly inhibited by DHEA treatment. These
      results show that DHEA reduces oxidative stress and the consequent increase of
      lipoxygenase pathway products induced by experimental diabetes in rat kidney;
      they also suggest that, by reducing the inflammatory response to oxidative
      stress, DHEA treatment might delay the progression of diabetic kidney disease.

PMID- 11595380
TI  - Cold-induced apoptosis in isolated rat hepatocytes: protective role of
      glutathione.
AB  - Liver conservation for transplantation is usually made at 2-4 degrees C. We
      studied the effect of rewarming to 37 degrees C for up to 3 h of rat hepatocytes
      kept at 4 degrees C for 20 h, modulating intracellular glutathione (GSH)
      concentration either with a GSH precursor (N-acetyl-L-cysteine, NAC), or with GSH
      depleting agents (diethylmaleate and buthionine sulfoximine, DEM/BSO). Untreated
      hepatocytes showed time-dependent production of reactive oxygen species (ROS),
      lipid peroxidation, chromatin condensation and membrane blebbing, decrease in GSH
      concentration, and protein sulfhydryl groups. Fluorochromatization with Propidium
      Iodide (PI) and Annexin V (AnxV) of cells rewarmed for 1 h caused an increase of
      AnxV-positive cells without PI staining and any observed lactate dehydrogenase
      leakage. TUNEL and DNA-laddering tests were negative for all times and
      treatments, indicating that apoptosis may occur without DNA fragmentation. Cold
      preservation and rewarming in the presence of NAC induced a significant
      improvement in the morphology, less oxidative stress and apoptosis. Conversely,
      DEM/BSO caused a marked deterioration of morphology, increase of oxidative stress
      and apoptosis. These results suggested that marked changes in GSH status might
      play a critical role in triggering apoptosis during cold preservation of isolated
      rat hepatocytes. NAC, added before rewarming, might represent a therapeutic
      approach for preventing the early events of apoptosis during cold storage.

PMID- 11595381
TI  - Differences in basal airway antioxidant concentrations are not predictive of
      individual responsiveness to ozone: a comparison of healthy and mild asthmatic
      subjects.
AB  - The air pollutant ozone induces both airway inflammation and restrictions in lung
      function. These responses have been proposed to arise as a consequence of the
      oxidizing nature of ozone, depleting endogenous antioxidant defenses with ensuing
      tissue injury. In this study we examined the impact of an environmentally
      relevant ozone challenge on the antioxidant defenses present at the surface of
      the lung in two groups known to have profound differences in their antioxidant
      defense network: healthy control (HC) and mild asthmatic (MA) subjects. We
      hypothesized that baseline differences in antioxidant concentrations within the
      respiratory tract lining fluid (RTLF), as well as induced responses, would
      predict the magnitude of individual responsiveness. We observed a significant
      loss of ascorbate (ASC) from proximal (-45.1%, p <.01) and distal RTLFs (-11.7%,
      p <.05) in healthy subjects 6 h after the end of the ozone challenge. This was
      associated (Rs, -0.71, p <.01) with increased glutathione disulphide (GSSG) in
      these compartments (p =.01 and p <.05). Corresponding responses were not seen in
      asthmatics, where basal ASC concentrations were significantly lower (p <.01) and
      associated with elevated concentrations of GSSG (p <.05). In neither group was
      any evidence of lipid oxidation seen following ozone. Despite differences in
      antioxidant levels and response, the magnitude of ozone-induced neutrophilia
      (+20.6%, p <.01 [HC] vs. +15.2%, p =.01 [MA]) and decrements in FEV(1) (-8.0%, p
      <.01 [HC] vs. -3.2%, p <.05 [MA]) did not differ between the two groups. These
      data demonstrate significant differences between the interaction of ozone with
      RTLF antioxidants in MA and HC subjects. These responses and variations in basal
      antioxidant defense were not, however, useful predictive markers of group or
      individual responsiveness to ozone.

PMID- 11595382
TI  - Reaction of tetrahydrobiopterin with superoxide: EPR-kinetic analysis and
      characterization of the pteridine radical.
AB  - It has been shown that BH(4) ameliorates endothelial dysfunction associated with
      conditions such as hypertension, cigarette smoking, and diabetes. This effect has
      been proposed to be due to a superoxide scavenging activity of BH(4). To examine
      this possibility we determined the rate constant for the reaction between BH(4)
      and superoxide using electron paramagnetic resonance (EPR) spin trapping
      competition experiments with 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide
      (DEPMPO). We calculated a rate constant for the reaction between BH(4) and
      superoxide of 3.9 +/- 0.2 x 10(5) M(-1)s(-1) at pH 7.4 and room temperature. This
      result suggests that superoxide scavenging by BH(4) is not a major reaction in
      vivo. HPLC product analysis showed that 7,8-BH(2) and pterin are the stable
      products generated from the reaction. The formation of BH(4) cation radical
      (BH(4)(*+)) was demonstrated by direct EPR only under acidic conditions. Isotopic
      substitution experiments demonstrated that the BH(4)(*+) is mainly delocalized on
      the pyrazine ring of BH(4). In parallel experiments, we investigated the effect
      of ascorbate on 7,8-BH(2) reduction and eNOS activity. We demonstrated that
      ascorbate does not reduce 7,8-BH(2) to BH(4), nor does it stimulate nitric oxide
      release from eNOS incubated with 7,8-BH(2). In conclusion, it is likely that
      BH(4)-dependent inhibition of superoxide formation from eNOS is the mechanism
      that better explains the antioxidant effects of BH(4) in the vasculature.

PMID- 11595384
TI  - Modification of ferritin during iron loading.
AB  - Recombinant human ferritin loaded with iron via its own ferroxidase activity did
      not sediment through a sucrose-density gradient as a function of iron content.
      Analysis of the recombinant ferritin by native PAGE demonstrated an increase in
      altered migration pattern of the ferritins with increasing sedimentation,
      indicating an alteration of the overall charge of ferritin. Additionally,
      analysis of the ferritin by SDS-PAGE under nonreducing conditions demonstrated
      that the ferritin had formed large aggregates, which suggests disulfide bonds are
      involved in the aggregation. The hydroxyl radical was detected by electron spin
      resonance spectroscopy during iron loading into recombinant ferritin by its own
      ferroxidase activity. However, recombinant human ferritin loaded with iron in the
      presence of ceruloplasmin sedimented through a sucrose-density gradient similar
      to native ferritin. This ferritin was shown to sediment as a function of iron
      content. The addition of ceruloplasmin to the iron loading assay eliminated the
      detection of the DMPO-*OH adduct observed during loading using the ferroxidase
      activity of ferritin. The elimination of the DMPO-*OH adduct was determined to be
      due to the ability of ceruloplasmin to completely reduce oxygen to water during
      the oxidation of the ferrous iron. The implications of these data for the present
      models for iron uptake into ferritin are discussed.

PMID- 11595383
TI  - Effect of iron and manganese on hydroxyl radical production by 6-hydroxydopamine:
      mediation of antioxidants.
AB  - 6-Hydroxydopamine (6-OHDA) neurotoxicity has often been related to the generation
      of free radicals. Here we examined the effect of the presence of iron (Fe(2+) and
      Fe(3+)) and manganese and the mediation of ascorbate, L-cysteine (CySH),
      glutathione (GSH), and N-acetyl-CySH on hydroxyl radical (*OH) production during
      6-OHDA autoxidation. In vitro, the presence of 800 nM iron increased (> 100%) the
      production of *OH by 5 microM 6-OHDA while Mn(2+) caused a significant reduction
      (72%). The presence of ascorbate (100 microM) induced a continuous generation of
      *OH while the presence of sulfhydryl reductants (100 microM) limited this
      production to the first minutes of the reaction. In general, the combined action
      of metal + antioxidant increased the *OH production, this effect being
      particularly significant (> 400%) with iron + ascorbate. In vivo, tyrosine
      hydroxylase immunohistochemistry revealed that intrastriatal injections of rats
      with 6-OHDA (30 nmol) + ascorbate (600 nmol), 6-OHDA + ascorbate + Fe(2+) (5
      nmol), and 6-OHDA + ascorbate + Mn(2+) (5 nmol) caused large striatal lesions,
      which were markedly reduced (60%) by the substitution of ascorbate by CySH.
      Injections of Fe(2+) or Mn(2+) alone showed no significant difference to those of
      saline. These results clearly demonstrate the role of ascorbate as an essential
      element for the neurotoxicity of 6-OHDA, as well as the diminishing action of
      sulfhydryl reductants, and the negligible effect of iron and manganese on 6-OHDA
      neurotoxicity.

PMID- 11595385
TI  - The consequences of hydroxyl radical formation on the stoichiometry and kinetics
      of ferrous iron oxidation by human apoferritin.
AB  - Despite previous detection of hydroxyl radical formation during iron deposition
      into ferritin, no reports exist in the literature concerning how it might affect
      ferritin function. In the present study, hydroxyl radical formation during Fe(II)
      oxidation by apoferritin was found to be contingent on the "ferroxidase" activity
      (i.e., H subunit composition) exhibited by apoferritin. Hydroxyl radical
      formation was found to affect both the stoichiometry and kinetics of Fe(II)
      oxidation by apoferritin. The stoichiometry of Fe(II) oxidation by apoferritin in
      an unbuffered solution of 50 mM NaCl, pH 7.0, was approximately 3.1 Fe(II)/O(2)
      at all iron-to-protein ratios tested. The addition of HEPES as an alternate
      reactant for the hydroxyl radical resulted in a stoichiometry of about 2
      Fe(II)/O(2) at all iron-to-protein ratios. HEPES functioned to protect
      apoferritin from oxidative modification, for its omission from reaction mixtures
      containing Fe(II) and apoferritin resulted in alterations to the ferritin
      consistent with oxidative damage. The kinetic parameters for the reaction of
      recombinant human H apoferritin with Fe(II) in HEPES buffer (100 mM) were: K(m) =
      60 microM, k(cat) = 10 s(-1), and k(cat)/K(m) = 1.7 x 10(5) M(-1) x (-1).
      Collectively, these results contradict the "crystal growth model" for iron
      deposition into ferritin and, while our data would seem to imply that the
      ferroxidase activity of ferritin is adequate in facilitating Fe(II) oxidation at
      all stages of iron deposition into ferritin, it is important to note that these
      data were obtained in vitro using nonphysiologic conditions. The possibility that
      these findings may have physiological significance is discussed.

PMID- 11595386
TI  - Strain-dependent high-level expression of a transgene for manganese superoxide
      dismutase is associated with growth retardation and decreased fertility.
AB  - Manganese superoxide dismutase (MnSOD) is essential in protecting mitochondria
      against the damaging effects of superoxide radicals (O(2)(*-)), and increased
      expression of MnSOD protects cells and transgenic animals from various forms of
      oxidative stress. In addition, increased levels of MnSOD have been shown to slow
      down cell growth and induce differentiation. To study the effects of high MnSOD
      levels in vivo, we generated a series of transgenic mice using a mouse genomic
      sequence under control of the endogenous promoter. Four transgenic lines produced
      by pronuclear DNA injection exhibited up to 2-fold elevated MnSOD levels in brain
      and heart. However, using an embryonic stem cell approach, a line having 10-fold
      elevated MnSOD levels in the brain and 6- to 7-fold elevated levels in the heart
      and kidney was generated. Surprisingly, the genetic background of this transgenic
      line influenced the expression level of the transgene, with DBA/2 (D2) and
      C57BL/6 (B6) mice exhibiting low- and high-level transgene expression,
      respectively. This difference was the result of an increased transcription rate
      of the transgene. High-level MnSOD expression in B6 animals was associated with
      small size, male infertility, and decreased female fertility. These features are
      absent on the D2 background and indicate that high levels of MnSOD activity may
      interfere with normal growth and fertility.

PMID- 11595387
TI  - Early developmental milestones in adult schizophrenia and other psychoses. A 31
      year follow-up of the Northern Finland 1966 Birth Cohort.
AB  - Delayed childhood development may precede adult psychoses. We tested this
      hypothesis in a large, general population birth cohort (n=12058) followed to age
      31 years. The ages at which individuals learned to stand, walk, speak, and became
      potty-trained (bowel control) and dry (bladder control), were recorded at a 1
      year examination. Psychiatric outcome was ascertained through linkage to a
      national hospital discharge register. Cumulative incidence of DSM-III-R
      schizophrenia, other psychoses and non-psychotic disorders were stratified
      according to the timing of milestones and compared within the cohort using
      internal standardization. 100 cases of DSM-III-R schizophrenia, 55 other
      psychoses, and 315 non-psychotic disorders were identified. The ages at learning
      to stand, walk and become potty-trained were each related to subsequent incidence
      of schizophrenia and other psychoses. Compared with the whole cohort, earlier
      milestones reduced, and later milestones increased, the risk in a linear manner.
      These developmental effects were not seen for non-psychotic outcomes. The
      findings support hypotheses regarding psychosis as having a developmental
      dimension with precursors apparent in early life.

PMID- 11595388
TI  - Estimated yield of early detection of prodromal or first episode patients by
      screening first degree relatives of schizophrenic patients.
AB  - Screening a population of relatives of current schizophrenic patients could be an
      efficient means to accrue a sample of early first episode or prodromal patients
      for a prediction study or an intervention study. The risk of new onset
      schizophrenia cases in any one year in a population of relatives depends on the
      number of schizophrenic probands and three additional factors: (1) the age of
      onset distribution for schizophrenia; (2) the lifetime risk of the at-risk group
      of relatives selected; and (3) the number of at-risk relatives per proband and
      their age distribution. Estimates are made for each of these parameters, and
      calculations are presented. The base model suggests that screening all siblings
      and children of patients with schizophrenia would yield approximately 19 new
      cases of schizophrenia per year per 10,000 relatives screened. The results of the
      calculation are relatively insensitive to reasonable variation of most model
      parameter estimates. The yield of new cases obtained by screening relatives of
      current patients appears to be low if the purpose is to recruit a sample for an
      early intervention study over a relatively short period of time.

PMID- 11595389
TI  - Duration of untreated psychosis as a predictor of outcome in first-episode
      schizophrenia: a retrospective study.
AB  - The aim of this study was to investigate possible clinical predictors of the
      outcome of first-episode schizophrenia. The clinical charts of the first episode
      of psychosis and the follow-up period over at least 4 years for 67 DSM-III-R
      schizophrenic patients were reviewed. According to the number of psychotic
      relapses observed during the follow-up period, patients were sub-divided into two
      groups: mono- and multi-episode patients. The main demographic and clinical
      variables recorded at the first episode were compared between the two groups. A
      logistic regression analysis was performed to test a model for the possible
      predictors of the two different patterns of outcome.Multi-episode patients had an
      earlier onset of the illness and a longer "duration of untreated psychosis"
      (DUP), defined as the interval between the onset of the first psychotic symptoms
      and the first antipsychotic treatment. The Brief Psychiatric Rating Scale (BPRS)
      total scores were lower and the "avolition/apathy" scores of the scale for the
      assessment of negative symptoms (SANS) were higher in multi-episode patients. The
      logistic regression analysis results confirmed the DUP and the pre-treatment BPRS
      scores to be significant predictors of the outcome. These findings confirm that
      the timing in recognizing and treating the early symptoms of schizophrenia, even
      when subtle, is a core issue for the clinical management of the disorder.

PMID- 11595390
TI  - A longitudinal study of hippocampal volume in first episode psychosis and chronic
      schizophrenia.
AB  - Brain abnormalities have been identified in patients with schizophrenia, but what
      is unclear is whether these changes are progressive over the course of the
      disorder. In this longitudinal study, hippocampal and temporal lobe volumes were
      measured at two time points in 30 patients with first episode psychosis (mean
      follow-up interval=1.9 years, range 0.54-4.18 years) and 12 with chronic
      schizophrenia (mean follow-up interval=2.3 years, range 1.03-4.12 years) and
      compared to 26 comparison subjects (mean follow-up interval 2.2 years, range 0.86
      4.18 years). Hippocampal, temporal lobe, whole-brain and intracranial volumes
      (ICV) were estimated from high-resolution magnetic resonance images. Only whole
      brain volume showed significant loss over the follow-up interval in both patient
      groups. The rate of this volume loss was not different in the first episode group
      compared to the chronic group. There were no changes in either hippocampal or
      temporal lobe volumes. The negative findings for the hippocampus and temporal
      lobes may mean that the abnormalities in these regions are stable features of
      schizophrenia. Alternatively, the period before the onset of frank psychotic
      symptoms may be the point of greatest risk for progressive change.

PMID- 11595391
TI  - An fMRI study of reduced left prefrontal activation in schizophrenia during
      normal inhibitory function.
AB  - Functional magnetic resonance imaging (fMRI) was used to investigate the
      hypothesis that schizophrenia is associated with a dysfunction of prefrontal
      brain regions during motor response inhibition. Generic brain activation of six
      male medicated patients with schizophrenia was compared to that of seven healthy
      comparison subjects matched for sex, age, and education level while performing
      'stop' and 'go-no-go' tasks. No group differences were observed in task
      performance. Patients, however, showed reduced BOLD signal response in left
      anterior cingulate during both inhibition tasks and reduced left rostral
      dorsolateral prefrontal and increased thalamus and putamen BOLD signal response
      during stop task performance. Despite good task performance, patients with
      schizophrenia thus showed abnormal neural network patterns of reduced left
      prefrontal activation and increased subcortical activation when challenged with
      motor response inhibition.

PMID- 11595392
TI  - Language lateralization in schizophrenia, an fMRI study.
AB  - Anatomical studies have shown that cerebral asymmetry is reduced in
      schizophrenia. Functional asymmetry appears to be reduced also, as was shown with
      dichotic listening studies. These studies, however, have not revealed whether
      reduced lateralization is the result of decreased language activity of the left
      hemisphere or whether it is the consequence of increased language-related
      activity in the right hemisphere. To elucidate this, we examined hemispheric
      dominance for language processing by means of functional MRI. Twelve
      schizophrenic patients and twelve healthy controls were scanned while they were
      engaged in a verb-generation and a semantic decision task. Activation was
      measured bilaterally in the frontal, temporal and temporo-parietal language
      areas, and a laterality index was derived from activity in these regions of
      interest in the left and the right hemispheres. Clinical symptoms were rated at
      the time of scanning. The results indicate that language processing is less
      lateralized in patients than in controls (a mean laterality index of 0.35 versus
      0.63, respectively, difference p<0.01). Analysis of variance of the extent of
      activity, i.e. numbers of active voxels, revealed a significant hemisphere by
      group interaction (F(1,22)=11.2, p<0.001), which was due to increased activation
      in the right hemisphere of the patients (post hoc t-test p<0.05). We found no
      evidence of reduced activity in the left hemisphere. Further analysis of clinical
      symptoms rated prior to scanning revealed that decreased language lateralization
      was associated with more severe hallucinations (r=-0.54, p<0.05). We postulate
      that decreased language lateralization in schizophrenia may result from failure
      to inhibit the right hemisphere.

PMID- 11595393
TI  - Functional asymmetry in schizophrenic patients during auditory speech processing.
AB  - In two experiments, functional laterality and interhemispheric transfer was
      investigated in schizophrenic patients (n=14) and healthy controls (n=17). In
      Experiment 1, words and pseudowords were presented either to the left or right
      ear (monaural condition) or simultaneously to both ears (binaural condition). In
      Experiment 2, subjects had to discriminate two tones differing in frequency
      during monaural and binaural stimulation. Healthy controls showed a right ear
      advantage (REA) for word stimuli, indicating left-hemispheric superiority for
      word processing. The same lateralization pattern was found in schizophrenic
      patients, indicating unimpaired functional lateralization of auditory language
      processing. In both groups, no REA was found for pseudowords resulting in
      significant WordnessxEar interactions. When presented binaurally, auditory
      processing of words and pseudowords did not differ significantly from any of the
      two monaural conditions. Tone discrimination did not lead to any ear asymmetry.
      The results show normal patterns of functional asymmetry during auditory language
      processing and tone discrimination in schizophrenic patients.

PMID- 11595394
TI  - Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses.
AB  - Disturbed neural development has been postulated as a crucial factor in the
      pathophysiology of schizophrenic psychoses. The neurobiochemical basis for such
      changes of cytoarchitecture and changed neural plasticity could involve an
      alteration in the regulation of neurotrophic factors. In order to test this
      hypothesis, BDNF and NT-3 levels in post-mortem brain tissue from schizophrenic
      patients were determined by ELISA. There was a significant increase in BDNF
      concentrations in cortical areas and a significant decrease of this neurotrophin
      in hippocampus of patients when compared with controls. NT-3 concentrations of
      frontal and parietal cortical areas were significantly lower in patients than in
      controls. These findings lend further evidence to the neurotrophin hypothesis of
      schizophrenic psychoses which proposes that alterations in expression of
      neurotrophic factors could be responsible for neural maldevelopment and disturbed
      neural plasticity, thus being an important event in the etiopathogenesis of
      schizophrenic psychoses.

PMID- 11595396
TI  - Low GSK-3 activity in frontal cortex of schizophrenic patients.
AB  - Glycogen synthase kinase-3 (GSK-3) (EC 2.7.1.37) is a protein kinase highly
      abundant in brain and involved in signal transduction cascades of multiple
      cellular processes, particularly neurodevelopment. Two forms of the enzyme, GSK
      3alpha and -3beta have been previously identified. We have previously reported
      reduced GSK-3beta protein levels in postmortem frontal cortex of schizophrenic
      patients. In an attempt to explore whether reduction of GSK-3beta levels is brain
      region specific we examined it in occipital cortex. In order to find out if the
      reduction in frontal cortex is reflected in altered activity we measured GSK-3
      enzymatic activity in this brain region. Western-blot analysis of GSK-3beta was
      carried out in postmortem occipital cortex of 15 schizophrenic, 15 bipolar, and
      15 unipolar patients, and 15 normal controls. GSK-3 activity was measured by
      quantitating the phosphorylation of the specific substrate phospho-CREB in the
      frontal cortex specimens. GSK-3beta levels in occipital cortex did not differ
      between the four diagnostic groups. GSK-3 activity in the frontal cortex of
      schizophrenic patients was 45% lower than that of normal controls (0.196+/-0.082
      and 0.357+/-0.084 pmol/mg proteinxmin, respectively; Kruskal-Wallis analysis: chi
      square=8.27, df=3, p=0.04). The other two diagnostic groups showed no difference
      from the control group. Our results are consistent with the notion that
      schizophrenia involves neurodevelopmental pathology.

PMID- 11595395
TI  - Reduced NAA in the thalamus and altered membrane and glial metabolism in
      schizophrenic patients detected by 1H-MRS and tissue segmentation.
AB  - Functional and structural abnormalities in the thalamus as well as a generalized
      phospholipid membrane disorder have been implicated in the pathogenesis of
      schizophrenic psychosis. To determine whether thalamic neuronal abnormalities and
      altered membrane-associated metabolites can be detected in schizophrenic
      patients, we used in vivo proton magnetic resonance spectroscopy (1H-MRS) in 32
      acutely-ill, medicated schizophrenic patients and 17 age-matched controls.
      Thalamic and white matter metabolite concentrations (myo-inositol (mI), choline
      containing compounds (Cho), total creatine (Cr) and N-acetylaspartate (NAA)) were
      estimated and corrected for atrophy (CSF) and gray and white matter contributions
      (GM, WM) by use of image-based voxel segmentation. Thalamic NAA was significantly
      reduced in schizophrenic patients, whereas Cho and mI were significantly
      increased in the parietal white matter. White matter Cr was significantly
      elevated in patients and correlated positively with the brief psychiatric rating
      scores (BPRS). Regional metabolite levels were inversely associated with GM and
      WM content reaching significance for mI and Cr in the thalamus and Cho and NAA in
      the white matter. Reduced NAA in the left thalamus of schizophrenic patients
      confirms and extends previous spectroscopic data and agrees well with histologic
      and imaging findings of reduced neuronal density and volume. Elevated Cho in line
      with 31P-MRS studies suggests increased myelin degradation thus further
      supporting a generalized membrane disorder in schizophrenic patients. In
      addition, we demonstrate the need to correct metabolite concentrations for
      regional tissue composition in studies employing patients with altered brain
      morphology.

PMID- 11595397
TI  - Studies on dopaminergic and GABAergic markers in striatum reveals a decrease in
      the dopamine transporter in schizophrenia.
AB  - Changes in the interaction between dopaminergic and GABAergic systems in the
      striatum have been suggested to be important in the pathology of schizophrenia.
      If that hypothesis is correct, these changes could produce inter-related changes
      in the dopaminergic and GABAergic systems in the striatum from schizophrenic
      subjects. To test this proposition we measured important markers on dopaminergic
      and GABAergic neurons in striatum obtained post-mortem from schizophrenic and non
      schizophrenic subjects. There was a significant decrease in the density of the
      dopamine transporter (mean+/-SEM: 230+/-31 vs. 334+/-22fmol/mg ETE; P=0.01), but
      not nitric oxide synthase, dopamine D(2)-like, D(1)-like, D(3) or GABA(A)
      receptors in subjects with schizophrenia. There were no inter-related changes in
      the dopaminergic or GABAergic markers. In the schizophrenic subjects, the density
      of dopamine D(1)-like receptors decreased with age and was positively correlated
      with the density of dopamine D(2)-like receptors. This study does not readily add
      weight to the hypothesis that changes in the interaction between dopamine and
      GABA in the striatum are important in the pathology of schizophrenia. However,
      our findings could indicate that changes in the dopamine transporter within the
      striatum, either because of decreased transporter numbers per se or as a result
      of innervating neuronal loss, may be involved in the pathology of the illness.

PMID- 11595398
TI  - Decreased striatal dopamine transporter binding in vivo in chronic schizophrenia.
AB  - We have previously reported that average striatal dopamine transporter (DAT)
      binding in vivo is unaltered in neuroleptic-naive first-episode schizophrenic
      patients [Laakso et al., Am. J. Psychiatry 157 (2000) 269]. However, as it has
      been suggested that some of the brain changes in schizophrenia may vary depending
      on the illness phase, we studied DAT density in eight stable, medicated chronic
      schizophrenic patients and eight matched controls using positron emission
      tomography and [18F]CFT, a marker of dopamine nerve terminals. [18F]CFT binding
      potentials were significantly lower in chronic schizophrenic patients than in
      controls, both in the caudate and the putamen (-9 to -16%). Together with the
      finding of unchanged average striatal DAT levels in first-episode patients and
      relative insensitivity of striatal [18F]CFT binding to endogenous dopamine and
      neuroleptic drugs, the result is in line with a relative loss of striatal
      dopaminergic nerve terminals and/or decreased expression of DAT in a subset of
      chronic schizophrenic patients.

PMID- 11595399
TI  - Phospholipid patterns of erythrocytes in schizophrenia: relationships to
      symptomatology.
AB  - The phospholipid composition of red blood cells (RBC) from 32 haloperidol-treated
      schizophrenic patients, classified according to the positive and negative
      syndrome scale (PANSS) as showing either predominantly positive or predominantly
      negative symptoms, was determined and compared with that of normal controls.
      While the levels of phosphatidylcholine and phosphatidylserine were similar in
      all three groups, sphingomyelin (SM) and phosphatidylethanolamine (PE) were,
      respectively, increased and decreased in RBCs of schizophrenic patients. In both
      patient groups, the SM/PE ratios correlated directly with the PANSS negative
      symptom scale scores and inversely with the positive symptom scale scores.
      However, the inverse changes in the contents of SM and PE were much more
      expressed in the negative group. It is suggested that a main source of that
      difference is a higher activity of the polyunsaturated acid-selective
      phospholipase A(2) in the negative syndrome patients than in the positive
      syndrome and control groups.

PMID- 11595400
TI  - Identification of antibodies to heat shock proteins 90 kDa and 70 kDa in patients
      with schizophrenia.
AB  - OBJECTIVES: Recent reports of antibodies to heat shock proteins 60kDa (HSP60) and
      HSP70 suggested that antibodies to the heat shock protein that plays a protective
      role against environmental stresses in a cell might be related to the
      pathogenesis of schizophrenia, although the antibody to HSP90 had not yet been
      identified in patients with schizophrenia. In this study, we tried to elucidate
      the specific involvement of the autoimmunity to HSPs in the pathogenesis and
      development of schizophrenia. METHODS: Antibodies to HSP90 and HSP70 in 90
      patients with schizophrenia and in 83 normal controls were measured by enzyme
      linked immunosorbent assay (ELISA) coupled with the avidin-biotin system. In the
      patients, the association between antibody levels and clinical variables were
      sought. In addition, changes in antibody levels after treatment with
      antipsychotic medication were investigated. RESULTS: Eighteen (20.0%) of the 90
      patients showed 'high' levels of antibody to HSP90 above a cutoff value, and 28
      (31.1%) of those showed 'high' antibody levels to HSP70. On the other hand, only
      four (4.8%) of the normal controls showed 'high' HSP90 antibody levels, and one
      (1.2%) of these showed 'high' antibody level to HSP70. The distribution of
      elevated HSP90 antibody was significantly associated with that of elevated HSP70
      antibody in the patients with schizophrenia. The patients with 'high' levels of
      antibody to HSP70 showed higher initial Brief Psychiatric Rating Scale (BPRS)
      scores and showed greater clinical improvement than those with 'low' levels,
      while the patients with 'high' levels of antibody to HSP90 did not. The frequency
      of patients with high levels of antibody to HSP70 was decreased significantly
      after 6 weeks of antipsychotic treatment, while the frequency of patients with
      high levels of antibody to HSP90 was not. CONCLUSIONS: Our results presented the
      presence of abnormal immune reactivity involving antibody to HSP90 and antibody
      to HSP70 in a subset of patients with schizophrenia. Differential patterns of
      distribution, of the association with clinical symptom severity, and of the
      changes of levels with treatment suggested the possibility that these two
      antibodies might be involved specifically in the pathogenesis of schizophrenia.

PMID- 11595401
TI  - Polymorphisms of mu and delta opioid receptor genes and tardive dyskinesia in
      patients with schizophrenia.

PMID- 11595402
TI  - Effect of the CYP2D6 genotype on prolactin concentration in schizophrenic
      patients treated with haloperidol.

PMID- 11595403
TI  - Soluble interleukin 2 receptor levels in acute and stable schizophrenia.

PMID- 11595404
TI  - Human germline mutation in the factor IX gene.
AB  - The molecular epidemiology of factor IX germline mutations in patients with
      hemophilia B has been studied in detail because it is an advantageous model for
      analyzing recent germline mutations in humans. It is estimated that mutations
      have been defined in the majority of nucleotides that are the target for
      mutation. The likelihood that a factor IX missense mutation will cause disease
      correlates with the degree of evolutionary conservation of the amino acid.
      Mutation rates per base-pair have been estimated after careful consideration and
      correction for biases, predicting about 76 de novo mutations per generation per
      individual resulting in 0.3 deleterious changes. The male-to-female sex ratio of
      mutation varies with the type of mutation. There is evidence for a maternal age
      effect and an excess of non-CpG G:C to A:T transitions. The factor IX mutation
      pattern is similar among geographically, racially and ethnically diverse human
      populations. The data support primarily endogenous mechanisms of germline
      mutation in the factor IX gene. Mutations at splice junctions are compatible with
      simple rules for predicting disease causing mutations.

PMID- 11595405
TI  - Accumulation of oxidative DNA damage, 8-oxo-2'-deoxyguanosine, and change of
      repair systems during in vitro cellular aging of cultured human skin fibroblasts.
AB  - Effects of in vitro cellular aging on the content of 8-oxo-2'-deoxyguanosine, a
      typical oxidation product of DNA bases, were examined in cultured human skin
      fibroblasts. The 8-oxo-2'-deoxyguanosine content in the DNA of TIG-3S cells
      established from skin tissues of a fetal donor increased immediately before the
      cessation of proliferation. TIG-114 and TIG-104 cells established from skin
      tissues of adult and aged donors, respectively, showed similar changes in 8-oxo
      2'-deoxyguanosine content during in vitro cellular aging. The accumulation of 8
      oxo-2'-deoxyguanosine in late-passage cells was dependent on the number of cell
      divisions, and not on the cultivation time. Increases in the activities of
      superoxide dismutase and glutathione peroxidase were observed prior to the
      increase in 8-oxo-2'-deoxyguanosine content, while the catalase activity
      decreased gradually during in vitro cellular aging at late-passage. Furthermore,
      the activities of 8-oxo-2'-deoxyguanosine endonuclease and DNA polymerases
      decreased with the progression of proliferation. These results indicate that
      defense systems against oxidative stress in late-passage cells remain
      sufficiently active before the cessation of cell division, but that repair
      systems against oxidative damage decay at late-passage. Oxidative stress beyond
      the antioxidant capacity and/or repair activity seems to result in an
      accumulation of 8-oxo-2'-deoxyguanosine in late-passage cells.

PMID- 11595406
TI  - Phenotype of FAECB (Facility for Automated Experiments in Cell Biology) Chinese
      hamster ovary mutants with minimal UV-sensitivity.
AB  - The Facility for Automated Experiments in Cell Biology (FAECB) collection of over
      200 lines of ultraviolet (UV)-sensitive mutant Chinese hamster ovary (CHO) cells
      has previously been studied for complementation group assignment (CG), with
      representatives of rodent UV CGs 1-6 (ERCC1-6) and the new rodent XRCC9/FANCG
      group identified. Ten mutants from the collection, including a further six
      derived from wildtype AA8, three UV-sensitive double-mutants of CHO ERCC1 cell
      line UV4, and a UV-sensitive mutant of CHO XRCC1 cell line EM9, had not been
      assigned or characterized in these previous studies. These 10 mutants include 8
      with approximately 1.5-fold the UV-sensitivity of the parental line (AA8, EM9, or
      UV4), and 2 with about 2-fold the UV-sensitivity of AA8. The present study
      reports the partial characterization of these 10 mutants in terms of sensitivity
      to UV (with and without caffeine), ionizing radiation, mitomycin C (MMC) and
      ethyl methanesulfonate (EMS); proficiency in DNA repair (unscheduled DNA
      synthesis (UDS)); and UV-mutability. The phenotypes of the 10 cell lines were
      heterogeneous, a number showed reduced UDS or UV-sensitization by caffeine,
      whilst others showed marked sensitivity to EMS or MMC, and they may have
      mutations in different genes involved in nucleotide excision repair, post
      replicational repair, base excision repair or recombinational repair. Previous
      mutants isolated as part of the FAECB collection have proved to be extremely
      important in characterizing mammalian DNA repair processes and cloning human
      repair genes and these current mutants, whilst not as hypersensitive to UV, may
      still have the potential to make further contributions.

PMID- 11595407
TI  - Spontaneous and ultraviolet light-induced direct repeat recombination in
      mammalian cells frequently results in repeat deletion.
AB  - Recombination is enhanced by transcription and by DNA damage caused by
      ultraviolet light (UV). Recombination between direct repeats can occur by gene
      conversion without an associated crossover, which maintains the gross repeat
      structure. There are several possible mechanisms that delete one repeat and the
      intervening sequences (gene conversion associated with a crossover, unequal
      sister chromatid exchange, and single-strand annealing). We examined
      transcription-enhanced spontaneous recombination, and UV-induced recombination
      between neomycin (neo) direct repeats. One neo gene was driven by the inducible
      MMTV promoter. Multiple (silent) markers in the second neo gene were used to map
      conversion tracts. These markers are thought to inhibit spontaneous
      recombination, and our data suggest that this inhibition is partially overcome by
      high level transcription. Recombination was stimulated by transcription and by UV
      doses of 6-12J/m(2), but not by 18J/m(2). About 70% of spontaneous and UV-induced
      products were deletions. In contrast, only 3% of DSB-induced products were
      deletions. We propose that these product spectra differ because spontaneous and
      UV-induced recombination is replication-dependent, whereas DSB-induced
      recombination is replication-independent.

PMID- 11595408
TI  - Overexpression of Ogt reduces MNU and ENU induced transition, but not
      transversion, mutations in E. coli.
AB  - Studies of alkylation-induced mutations in Escherichia coli FX-11 revealed that
      both N-ethyl-N-nitrosourea (ENU) and N-methyl-N-nitrosourea (MNU) produced tRNA
      suppressor mutations (G:C to A:T) but only ENU produced a significant number of
      backmutations (A:T to G:C, A:T to T:A and A:T to C:G). Further, the ENU-induced
      transversions were absent in a UmuC-defective strain. This suggested that
      transition mutations could result from alkylation of guanine or thymine at the
      O(6)- and O(4)-positions, respectively, but that transversions might result from
      alkylation of thymine at the O(2)-position. To test this idea, the gene encoding
      O(6)-alkylguanine-DNA methyltransferase (ogt) was recombined into a plasmid to
      overexpress the cellular levels of this enzyme. Ogt protein can de-alkylate O(6)
      alkylguanine and O(4)-alkylthymine, but not O(2)-alkylthymine. Cells harboring
      the plasmid (or a control plasmid lacking the ogt gene) were exposed to different
      concentrations of MNU or ENU and the resulting mutations were analyzed. With
      either MNU or ENU, the frequency of GlnV(o) suppressors was reduced about 70-fold
      in the Ogt-overexpressing cells, suggesting that Ogt eliminated O(6)
      alkylguanine. Similarly, GlnU(o) suppressor frequencies were substantially
      reduced. In contrast, the reduction in frequency for the backmutations was
      slight, only about 2.5-fold with MNU and less than two-fold for ENU. However, DNA
      sequence analysis of the backmutations showed that only A:T to G:C transitions
      were affected by overexpression of Ogt, suggesting repair of O(4)-alkylthymine.
      The frequency of transversions, in comparison, was essentially unaltered. These
      results implicate O(2)-alkylthymine as a likely candidate for transversion
      mutagenesis induced by ENU.

PMID- 11595409
TI  - Repair of O(6)-methylguanine is not affected by thymine base pairing and the
      presence of MMR proteins.
AB  - Methylation at the O(6)-position of guanine (O(6)-MeG) by alkylating agents is
      efficiently removed by O(6)-methylguanine-DNA methyltransferase (MGMT),
      preventing from cytotoxic, mutagenic, clastogenic and carcinogenic effects of
      O(6)-MeG-inducing agents. If O(6)-MeG is not removed from DNA prior to
      replication, thymine will be incorporated instead of cytosine opposite the O(6)
      MeG lesion. This mismatch is recognized and processed by mismatch repair (MMR)
      proteins which are known to be involved in triggering the cytotoxic and genotoxic
      response of cells upon methylation. In this work we addressed three open
      questions. (1) Is MGMT able to repair O(6)-MeG mispaired with thymine (O(6)
      MeG/T)? (2) Do MMR proteins interfere with the repair of O(6)-MeG/T by MGMT? (3)
      Does MGMT show a protective effect if it is expressed after replication of DNA
      containing O(6)-MeG? Using an in vitro assay we show that oligonucleotides
      containing O(6)-MeG/T mismatches are as efficient as oligonucleotides containing
      O(6)-MeG/C in competing for MGMT repair activity, indicating that O(6)-MeG
      mispaired with thymine is still subject to repair by MGMT. The addition of MMR
      proteins from nuclear extracts, or of recombinant MutSalpha, to the in vitro
      repair assay did not affect the repair of O(6)-MeG/T lesions by MGMT. This
      indicates that the presence of MutSalpha still allows access of MGMT to O(6)
      MeG/T lesions. To elucidate the protective effect of MGMT in the first and second
      replication cycle after N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment,
      MGMT transfected CHO cells were synchronized and MGMT was inactivated by pulse
      treatment with O(6)-benzylguanine (O(6)-BG). Thereafter, the recovered cells were
      treated with MNNG and subjected to clonogenic survival assays. Cells which
      expressed MGMT in the first and second cell cycle were more resistant than cells
      which expressed MGMT only in the second (post-treatment) cell cycle. Cells which
      did not express MGMT in both cell cycles were most sensitive. This indicates that
      repair of O(6)-MeG can occur both in the first and second cell cycle after
      alkylation protecting cells from the killing effect of the lesion.

PMID- 11595410
TI  - SUVi and BACH1: a new subfamily of mammalian helicases?
AB  - The RecQ family of DNA helicases have been shown to be important for the
      maintenance of genomic integrity in prokaryotes and eukaryotes. Members of this
      family are genes responsible for cancer predisposition disorders like Bloom's
      syndrome, Werner's syndrome and Rothmund-Thomson syndrome. Here, we show the
      sequence homologies between two recently identified mammalian helicases, namely
      SUVi and BACH1. These two genes also share strong homologies with other members
      of the RecQ family. On the basis of published data and sequence analysis we
      suggest that SUVi/BACH1 may represent a novel subfamily of mammalian helicases,
      functioning in the processing of lesions induced by different genotoxic agents.

PMID- 11595412
TI  - Role of cyclooxygenase isoforms in gastric mucosal defence.
AB  - A complex system of interacting mediators exists in the gastric mucosa to
      strengthen its resistance against injury. In this system prostaglandins play an
      important role. Prostaglandin biosynthesis is catalysed by the enzyme
      cyclooxygenase (COX), which exists in two isoforms, COX-1 and COX-2. Initially
      the concept was developed that COX-1 functions as housekeeping enzyme, whereas
      COX-2 yields prostaglandins involved in pathophysiological reactions such as
      inflammation. In the gastrointestinal tract, the maintenance of mucosal integrity
      was attributed exclusively to COX-1 without a contribution of COX-2 and
      ulcerogenic effects of non-steroidal anti-inflammatory drugs (NSAIDs) were
      believed to be the consequence of inhibition of COX-1. Recent findings, however,
      indicate that both COX-1 and COX-2 either alone or in concert contribute to
      gastric mucosal defence. Thus, in normal rat gastric mucosa specific inhibition
      of COX-1 does not elicit mucosal lesions despite near-maximal suppression of
      gastric prostaglandin formation. When a selective COX-2 inhibitor which is not
      ulcerogenic when given alone is added to the COX-1 inhibitor, severe gastric
      damage develops. In contrast to normal gastric mucosa which requires simultaneous
      inhibition of COX-1 and COX-2 for breakdown of mucosal resistance, in the acid
      challenged rat stomach inhibition of COX-1 alone results in dose-dependent injury
      which is further increased by additional inhibition of COX-2 enzyme activity or
      prevention of acid-induced up-regulation of COX-2 expression by dexamethasone.
      COX-2 inhibitors do not damage the normal or acid-challenged gastric mucosa when
      given alone. However, when nitric oxide formation is suppressed or afferent
      nerves are defunctionalized, specific inhibition of COX-2 induces severe gastric
      damage. Ischemia-reperfusion of the gastric artery is associated with up
      regulation of COX-2 but not COX-1 mRNA. COX-2 inhibitors or dexamethasone augment
      ischemia-reperfusion-induced gastric damage up to four-fold, an effect abolished
      by concurrent administration of 16,16-dimethyl-PGE(2). Selective inhibition of
      COX-1 is less effective. Furthermore, COX-2 inhibitors antagonize the protective
      effect of a mild irritant or intragastric peptone perfusion in the rat stomach,
      whereas the protection induced by chronic administration of endotoxin is mediated
      by COX-1. Finally, an important function of COX-2 is the acceleration of ulcer
      healing. COX-2 is up-regulated in chronic gastric ulcers and inhibitors of COX-2
      impair the healing of ulcers to the same extent as non-selective NSAIDs. Taken
      together, these observations show that both COX isoenzymes are essential factors
      in mucosal defence with specific contributions in various physiological and
      pathophysiological situations.

PMID- 11595413
TI  - The ever-emerging anti-inflammatories. Have there been any real advances?
AB  - Gastrointestinal (GI) Adverse Drug Reactions (ADRs) from the NSAIDs are a major
      cause of morbidity and mortality in arthritic patients taking these drugs. The
      recent much heralded development of COX-2 selective drugs (celecoxib, rofecoxib),
      the objective of which has been to spare inhibition of the production of COX-1
      derived mucosal protective prostaglandins, may have represented an advance in
      reducing the risk of serious ADRs--ulcers and bleeding--but does not appear to
      have reduced the incidence of symptomatic side-effects (nausea, vomiting,
      epigastric pain/heartburn, abdominal discomfort) which are a major reason for
      withdrawal from NSAID therapy, especially in the long term. The rationale of COX
      2 selectivity from these newer drugs is controversial since there may be
      pharmacokinetic differences from established carboxylate-NSAIDs that accounts for
      their apparent lower ulcerogenicity. Moreover, concerns have been recently
      expressed that as COX-2 is important in ulcer healing, control of prostacyclin
      production and renal function that they may have adverse reactions from these
      effects. Indeed, recent reports of enhanced risk of congestive heart failure with
      rofecoxib are of importance and may relate to impaired prostacyclin production.
      Moreover, there are other therapeutic strategies that have yielded equally low
      ulcerogenic NSAIDs (e.g. the prodrug, nabumetone; the established COX-2
      inhibitory drug, nimesulide) and even the well-established NSAIDs ibuprofen and
      diclofenac have relatively low upper GI ulcerogenicity and have been used as
      benchmark standards in comparative trials of the newer "Oxib" drugs (celecoxib,
      rofecoxib). Much research interest has centred on the nitric oxide-donating
      NSAIDs (NO-NSAIDs). The rationale for donating NSAIDs being to counteract the
      vasoconstriction effects of NSAIDs but this has yet to be fully evaluated. It is
      not certain that this "antidote" approach will be acceptable as there may also be
      systemic effects of the nitrobutoxyl--or other NO-donors that may have
      toxicological consequences. Another strategy is the development of mixed COX-5
      lipoxygenase (LOX) inhibitors--the progenitors of which were benoxaprofen and BW
      755C. The rationale of reducing the potential for lipoxygenase mediated actions
      in the stomach (e.g. vasoconstriction, leucocyte accumulation). Clearly, the need
      to develop newer NSAIDs with lower risks of ulcers and bleeding as well as
      symptomatic ADRs is still representing a major challenge.

PMID- 11595414
TI  - Inhibition of both COX-1 and COX-2 is required for development of gastric damage
      in response to nonsteroidal antiinflammatory drugs.
AB  - We examined the gastric ulcerogenic property of selective COX-1 and/or COX-2
      inhibitors in rats, and investigated whether COX-1 inhibition is by itself
      sufficient for induction of gastric damage. Animals fasted for 18 h were given
      various COX inhibitors p.o., either alone or in combination, and they were killed
      8 h later. The nonselective COX inhibitors such as indomethacin, naproxen and
      dicrofenac inhibited PG production, increased gastric motility, and provoked
      severe gastric lesions. In contrast, the selective COX-2 inhibitor rofecoxib did
      not induce any damage in the stomach, with no effect on the mucosal PGE(2)
      contents and gastric motility. Likewise, the selective COX-1 inhibitor SC-560
      also did not cause gastric damage, despite causing a significant decrease in
      PGE(2) contents. The combined administration of SC-560 and rofecoxib, however,
      provoked gross damage in the gastric mucosa, in a dose-dependent manner. SC-560
      also caused a marked gastric hypermotility, whereas rofecoxib had no effect on
      basal gastric motor activity. On the other hand, the COX-2 mRNA was expressed in
      the stomach after administration of SC-560, while the normal gastric mucosa
      expressed only COX-1 mRNA but not COX-2 mRNA. These results suggest that the
      gastric ulcerogenic property of conventional NSAIDs is not accounted for solely
      by COX-1 inhibition and requires the inhibition of both COX-1 and COX-2. The
      inhibition of COX-1 up-regulates the COX-2 expression, and this may counteract
      the deleterious influences, such as gastric hypermotility and the subsequent
      events, due to a PG deficiency caused by COX-1 inhibition.

PMID- 11595415
TI  - Atropine-induced gastrointestinal cytoprotection dependences to the intact of
      vagal nerve against indomethacin-induced gastrointestinal mucosal and
      microvascular damage in rats.
AB  - The non-steroidal antiinflammatory drugs, such as an indomethacin (IND), cause
      mucosal ulceration and increase the mucosal vascular permeability in the
      gastrointestinal (GI) tract. Some exogenous agents, e.g. the atropine, can
      protect the GI mucosa against these ulcerogenic effects. The gastrointestinal
      functions and mucosal protection, however, are regulated by the vagal nerve. The
      aims of this study was to examine the dependence of atropine-induced GI
      cytoprotection to the vagal innervation against the development of IND-caused
      ulcers and microvascular damage in the mucosa of stomach and small intestine in
      rats. METHODS: the observations were carried out on CFY-strain rats. The mucosal
      damage was produced by subcutaneous administration of IND in a 20 mg/kg dose 24 h
      prior to the killing of animals at the same time as the start of atropine
      application, which was given in a small dose (0.1 mg/kg) every 5 h. The
      subdiaphragmatic bilateral surgical vagotomy was done 24 h before the experiment.
      The vascular permeability, indicated by the microvascular endothel damage, was
      measured by the appearance and concentration of intravenously administered Evans
      blue into the GI mucosa. The number and severity of mucosal lesions and the Evans
      blue content of mucosa were determined in the stomach and small intestine.
      RESULTS: (1) The IND caused mucosal ulcers and Evans blue extravasation into the
      mucosa of the stomach and small intestine. (2) The IND-induced mucosal ulceration
      and vascular permeability significantly decreased after atropine-administration
      in the same parts of GI tract. (3) The extent of cytoprotective effect of
      atropine against the IND was decreased after bilateral surgical vagotomy.
      CONCLUSIONS: (1) The IND causes microvascular endothel damage in the stomach and
      small intestinal. (2) The atropine has a cytoprotective effect in the stomach and
      small intestine against the aggressive effects of IND without decrease of gastric
      acid secretion. (3) The intact vagal nerve is necessary to the function of
      cytoprotective mechanisms of atropine against the IND.

PMID- 11595416
TI  - Protection by constitutively formed nitric oxide of intestinal damage induced by
      indomethacin in rats.
AB  - In the present study, we investigated a protective role of constitutively
      occurred nitric oxide (NO) against indomethacin-induced intestinal lesions in
      rats. Indomethacin (10 mg/kg) was given s.c. to animals without fasting, and the
      intestinal mucosa was examined for lesions 24 h later. The NOS inhibitor N(G)
      nitro-L-arginine methyl ester (L-NAME) was given s.c. 0.5 h before or 6 hr after
      indomethacin, while the NO donor (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3
      hexnamine (NOR-3) was given s.c. 0.5 h before indomethacin. Indomethacin caused
      hemorrhagic lesions in the small intestine, accompanied with an increase in
      intestinal motility and bacterial translocation. These lesions were markedly
      prevented or worsened, respectively, by later or prior administration of L-NAME
      (20 mg/kg), in a L-arginine-sensitive manner. The worsening effect of L-NAME (5
      20 mg/kg) on these lesions was dose-dependently observed in association with
      further enhancement of the bacterial translocation and intestinal hypermotility
      following indomethacin. By contrast, prior administration of NOR-3 (1-6 mg/kg)
      dose-dependently prevented the development of intestinal lesions, together with
      suppression of the bacterial translocation and intestinal hypermotility in
      response to indomethacin. On the other hand, both indomethacin and L-NAME
      decreased intestinal mucus and fluid (water) secretion in the small intestine,
      while NOR-3 increased these secretions. These results suggest that (1) NO
      occurred constitutively exerts a protective action against indomethacin-induced
      intestinal ulceration, and (2) this effect is related with prevention of
      bacterial translocation, the process functionally associated with increase of
      mucus and fluid secretions as well as inhibition of intestinal hypermotility.

PMID- 11595417
TI  - The effect of etodolac on bile salt and histamine-mediated gastric mucosal injury
      in the rat.
AB  - The effect of the selective cyclo-oxygenase-type-2 (COX-2) inhibitor etodolac on
      gastric mucosal integrity and gastric acid secretion was investigated in the rat.
      Etodolac was given in doses comparable with those being used in man for therapy
      of rheumatic conditions. The effect of etodolac was studied in the presence of a
      mild barrier breaker and in the presence of increased rates of endogenous acid
      secretion. In conscious pylorus-ligated rats, etodolac given intragastrically in
      16 or 32 mg /kg for 3 h did not by itself give rise to visible gastric mucosal
      injury. Etodolac, however, exacerbated gastric mucosal injury evoked by
      intragastric application of acidified sodium taurocholate (5 mM in 150 mM HCl) in
      a dose-dependent manner. This effect of edotolac was independent of changes in
      gastric acid secretory responses. In rats whose gastric acid secretion was
      stimulated by intraperitoneal histamine (5 mg/kg), and etodolac (given i.g. in
      doses of 16 or 32 mg/kg) also increased gastric mucosal injury caused by
      histamine dose-dependently in the 3-h pylorus-ligated rats. Etodolac decreased
      gastric mucus in the saline- and in the sodium taurocholate-treated rats. In
      urethane-anaesthetized acute gastric fistula rats, intragastric etodolac (32
      mg/kg) did not modify basal gastric acid secretion. Our data suggest that
      etodolac, a selective COX-2 inhibitor, impairs gastric mucosal resistance and can
      exacerbate gastric mucosal injury caused by other mucosal barrier breaking
      agents. Cyclooxygenase type-2 thus contributes to the gastric mucosal defences.

PMID- 11595418
TI  - Protection by aspirin of indomethacin-induced small intestinal damage in rats:
      mediation by salicylic acid.
AB  - Most of non-steroidal anti-inflammatory drugs (NSAIDs) except aspirin (ASA)
      produce intestinal damage in rats. In the present study, we re-examined the
      intestinal toxic effect of ASA in rats, in comparison with various NSAIDs, and
      investigated why ASA does not cause damage in the small intestine, in relation to
      its metabolite salicylic acid (SA). Various NSAIDs (indomethacin; 10 mg/kg;
      flurbiprofen; 20 mg/kg; naproxen; 40 mg/kg; dicrofenac; 40 mg/kg; ASA; 20-200
      mg/kg) were administered s.c., and the small intestinal mucosa was examined
      macroscopically 24 h later. All NSAIDs tested, except ASA, caused hemorrhagic
      lesions in the small intestine, with a decrease of mucosal PGE(2) contents. ASA
      did not provoke any damage, despite inhibiting (prostaglandin) PG production, and
      prevented the occurrence of intestinal lesions induced by indomethacin, in a dose
      related manner. This protective action of ASA was mimicked by the equimolar doses
      of SA (17.8-178 mg/kg). Indomethacin caused intestinal hypermotility, in
      preceding to the occurrence of lesion, and this event was followed by increases
      of enterobacterial translocation in the mucosa. Both ASA and SA prevented both
      the intestinal hypermotility and the bacterial translocation seen after
      indomethacin treatment. In addition, the protective effect of SA was not
      significantly influenced by either the adenosine deaminase or the adenosine
      receptor antagonists. Following administration of ASA, the blood SA levels
      reached a peak within 30 min and remained elevated for more than 7 h. These
      results suggest that SA has a cytoprotective action against indomethacin-induced
      small intestinal lesions, and this action may be associated with inhibition of
      the intestinal hypermotility and the bacterial translocation, but not mediated by
      endogenous adenosine. Failure of ASA to induce intestinal damage may be
      explained, at least partly, by a protective action of SA, the metabolite of ASA.

PMID- 11595419
TI  - Various ulcerogenic stimuli are potentiated by glucocorticoid deficiency in rats.
AB  - The effects of glucocorticoid deficiency with or without corticosterone
      replacement on susceptibility to gastric mucosal injury by various ulcerogenic
      stimuli have been evaluated in rats. Gastric erosions were induced in male rats
      by stimuli of different modalities and intensities: 20% ethanol (po), aspirin
      (300 mg/kg, ip), acidified aspirin (40 mM, po) and 100% acetic acid (applied to
      gastric serosa). Glucocorticoid supply was decreased by adrenalectomy or by
      delayed inhibitory action after a single pharmacological dose of cortisol (300
      mg/kg, ip) injected one week before the onset of ulcerogenic stimulus.
      Corticosterone for replacement (4 mg/kg, sc) was injected in rats with
      glucocorticoid deficiency 15 min before the onset of ulcerogenic stimulus. Plasma
      corticosterone levels were measured by fluorometry. Gastric erosions were
      quantitated by measuring the area of damage. Ulcerogenic stimuli induced both
      plasma corticosterone rise and gastric mucosal injury. The area of mucosal
      damages induced various stimuli ranged from small to extensive. Glucocorticoid
      deficiency significantly potentiated an ulcerogenic action of every ulcerogenic
      stimulus. Replacing corticosterone prevented or significantly decreased erosion
      potentiating effect of glucocorticoid deficiency. These results show that
      endogenous glucocorticoids released during ulcerogenic influences help gastric
      mucosa to resist a harmful action of both weak and strong ulcerogenic stimuli.

PMID- 11595420
TI  - Role of histamine H(3) receptors in the control of gastrointestinal motility. An
      overview.
AB  - Over the last few years, the biochemical and functional characterization of H(3)
      receptors has been a matter for extensive investigation, culminating in the
      cloning of the human, guinea pig and rat receptor protein from brain tissues.
      This discovery contributed to determine the distribution of receptors in the body
      and to define the molecular mechanisms which follow activation. The major
      breakthrough in the histamine H(3) receptor field came with the synthesis of
      selective and potent agonists and antagonists, which unravelled the function of
      this receptor subtype in the different tissues. As expected from the ubiquitous
      location of histamine in the body, histamine H(3) receptors have also been
      identified in virtually every tissue, although they are quantitatively less
      abundant than H(1) and H(2) receptors. Concerning the gastrointestinal tract,
      this new receptor subtype seems to have multiple cellular locations, which
      include neurons, enteric ganglia, paracrine and immune cells and, in some
      tissues, also smooth muscle cells. Therefore it might be regarded as a general
      regulatory system of different digestive functions, including motility. The
      effects mediated by histamine H(3)-receptors mainly reflect the presynaptic
      inhibition of the release of either excitatory or inhibitory neurotransmitters
      from the myenteric plexus. The molecular mechanism of presynaptic inhibition
      seems to involve a restriction of calcium entry into the nerve endings, but other
      mechanisms (reduction of cAMP), possibly associated to different H(3) receptor
      subtypes, may be involved. Despite the widespread distribution and the well
      defined inhibitory effects evoked in the majority of in vitro models of
      intestinal motility, no clear cut evidence of its involvement in the control of
      peristalsis could be provided. In vivo models of gastrointestinal transit,
      indeed, did not reveal a defined effect of histamine H(3) receptor ligands, even
      though the possibility of a central inhibition was pointed out in several
      studies. Therefore, it is not clear at the present what is the physiological
      meaning of the histamine H(3) receptor in the control of gastrointestinal
      motility and whether it could represent a potential target for novel therapeutic
      interventions in deranged motility, taking into account that human
      gastrointestinal tissues are apparently devoid of this receptor.

PMID- 11595421
TI  - Role of endogenous prostacyclin in gastric ulcerogenic and healing responses--a
      study using IP-receptor knockout mice.
AB  - Endogenous prostaglandins (PGs) play an important role in the cytoprotective and
      healing responses in the stomach, by altering various functions, i.e., an
      increase of the mucosal blood flow, yet the role of prostacyclin (PGI(2)) and its
      receptor (IP-receptor) in these responses remains unclarified. In the present
      study, we used IP-receptor knockout mice [IP (-/-)] and examined the importance
      of IP-receptors in gastric ulcerogenic, cytoprotective and healing responses in
      these animals. The studies included the ulcerogenic response to cold-restraint
      stress, the cytoprotective response to a mild irritant (20 mM taurocholate: TC)
      and capsaicin, and the healing response of chronic gastric ulcers induced by
      thermo-cauterization. We first checked the absence of IP-receptors by examining
      the effect of cicaprost (a PGI(2) agonist, topical mucosal application) on
      gastric mucosal blood flow and found that this agent increased the mucosal blood
      flow in wild-type [WT (+/+)] mice but not in IP (+/-) mice. Cold-restraint stress
      (4 h) induced gastric lesions in both groups of mice, but the severity of damage
      was significantly greater in IP (-/-) mice. Prior p.o. administration of both TC
      and capsaicin exhibited a marked cytoprotection against HCl/ethanol-induced
      gastric damage in WT (+/+) mice, both responses being significantly mitigated in
      the presence of indomethacin. The adaptive cytoprotection induced by TC was
      similarly observed in IP (-/-) mice, while the capsaicin protection was totally
      attenuated in the animals lacking IP receptors. On the other hand, the healing of
      gastric ulcers was significantly delayed by daily administration of indomethacin
      in WT (+/+) mice. However, this process was not altered in IP (-/-) mice. These
      results suggest that endogenous PGI(2) is involved in the gastric ulcerogenic
      response to stress, but not in the healing of pre-existing gastric ulcers. In
      addition, PGI(2) and its receptors may play a crucial role in capsaicin-induced
      gastric protection but not in the adaptive cytoprotection-induced by mild
      irritants.

PMID- 11595422
TI  - Reduction of colonic mucus by repeated short-term stress enhances experimental
      colitis in rats.
AB  - The role of stress in inflammatory bowel disease remains debated and few studies
      have tested the role of stress in conjunction with experimental animal models of
      colitis. In this investigation we tested the hypothesis that cold-restraint
      stress would adversely effect the severity of 2,4,6-trinitrobenzene sulfonic acid
      (TNBS)-induced colitis in rats, and examined mechanisms for the response. Results
      indicated that increasing intermittent prior exposures to stress significantly
      enhanced TNBS-induced colitis severity. An associated stress-induced decrease in
      colonic mucin glycoprotein content, reduction in goblet cells, and histochemical
      mucin suggested reduced mucin was a pathogenetic factor. Myeloperoxidase content
      increased and mast cell counts in the colon decreased but colonic permeability
      only temporarily increased with increasing stress exposure. Prior adrenalectomy
      or administration of an adrenergic blocking agent did not prevent the colonic
      changes to stress, but mast cell stabilization or inhibition of cholinergic
      pathways reduced the stress-induced colonic changes.

PMID- 11595423
TI  - Involvement of gastrin in gastric secretory and protective actions of N-alpha
      methyl histamine.
AB  - N alpha-methylhistamine (N alpha-MH) is one of an unusual metabolite of histamine
      that was found in Helicobacter pylori-infected stomachs and is believed to
      interact with specific histamine H(1), H(2) and H(3)-receptors to stimulate
      gastric acid secretion and gastrin release from isolated G-cells but the effects
      of N alpha-MH on gastric mucosal integrity have been little studied. This study
      was designed; (1) to compare the effect of exogenous N alpha-MH with that of
      standard histamine on gastric secretion and plasma gastrin levels in rats
      equipped with gastric fistula (series A); and (2) to assess the action of N alpha
      MH on gastric lesions induced by 100% ethanol (series B) in rats with or without
      removal of antral portion of the stomach (antrectomy). Rats of series B were
      pretreated intragastrically (i.g.) or intraperitoneally (i.p.) with N alpha-MH or
      histamine (0.1-2 mg/kg) 30 min prior to 100% ethanol (1.5 ml, i.g.) with or
      without: (1) vehicle (saline); (2) RPR 102681 (30 mg/kg i.p.), to block CCK
      B/gastrin receptors; and (3) ranitidine (40 mg/kg s.c.) to inhibit histamine H(2)
      receptors. The area of gastric lesions was determined planimetrically, gastric
      blood flow (GBF) was assessed by H(2)-gas clearance method and venous blood was
      collected for determination of plasma gastrin levels by radioimmunoassay (RIA). N
      alpha-MH and histamine dose-dependently increased gastric acid output (series A);
      the dose increasing this secretion by 50% (ED(50)) being 2 and 5 mg/kg i.g or
      i.p., respectively, and this effect was accompanied by a significant rise in
      plasma gastrin levels. Both, N alpha-MH and histamine attenuated dose-dependently
      the area of gastric lesions induced by 100% ethanol (series B) while producing
      significant rise in the GBF and plasma immunoreactive gastrin increments. These
      secretory, protective, hipergastrinemic and hyperemic effects of N alpha-MH and
      histamine were completely abolished by antrectomy, whereas pretreatment with RPR
      102681 attenuated significantly the N alpha-MH and histamine-induced protection
      against ethanol damage and accompanying hyperemia. Ranitidine, that produced
      achlorhydria and a further increase in plasma gastrin levels, failed to influence
      the N alpha-MH- and histamine-induced protection and accompanying rise in the
      GBF. We conclude that (1) N alpha-MH stimulates gastric acid secretion and
      exhibit gastroprotective activity against acid-independent noxious agents in the
      manner similar to that afforded by histamine; and (2) this protection involves an
      enhancement in the gastric microcirculation and release of gastrin acting via
      specific CCK-B/gastrin receptors but unexpectedly, appears to be unrelated to
      histamine H(2)-receptors.

PMID- 11595424
TI  - Comparative study on the appearance of various bioactive peptides in foregut
      derivates during the ontogenesis.
AB  - Bioactive peptides have an important multifunctional role in the gastrointestinal
      tract. In the present study we have investigated the dynamism of the appearance
      of PACAP (pituitary adenylate cyclase activating polypeptide), VIP (vasoactive
      intestinal polypeptide), gastrin, and secretin immunoreactivities in human
      foregut derivates during the ontogenesis using an immunohistochemical approach.
      None of these peptides were observed in the foregut derivates of an 8-week-old
      embryo. VIP immunoreactive nerve fibers appeared by the 11th week in the smooth
      muscle layers of the stomach. No other peptide immunoreactivities were observed
      of this stage. In 18- and 20-week old fetuses PACAP, secretin, and gastrin
      immunoreactive cells appeared in the developing glands of the stomach. In the
      duodenum gastrin immunoreactivity was present in the Lieberkuhn's glands and
      secretin immunoreactive cells were seen between the surface epithelial cells. In
      the pancreas secretin immunoreactivity was found in the Langerhans islets;
      however, PACAP immunreactivity was observed in the exocrine portion. The
      distribution of VIP fibers did not change during the fetal life and it was
      similar to the adult pattern. According to our results the appearance of PACAP,
      secretin, and gastrin in the developing glands suggests their role in the
      proliferation and differentiation of the epithelial derivates.

PMID- 11595425
TI  - Gastric mucosal integrity: gastric mucosal blood flow and microcirculation. An
      overview.
AB  - The stomach is in a state of continuous exposure to potentially hazardous agents.
      Hydrochloric acid together with pepsin constitutes a major and serious threat to
      the gastric mucosa. Reflux of alkaline duodenal contents containing bile and
      pancreatic enzymes are additional important injurious factors of endogenous
      origin. Alcohol, cigarette smoking, drugs and particularly aspirin and aspirin
      like drugs, and steroids are among exogenous mucosal irritants that can inflict
      mucosal injury. The ability of the stomach to defend itself against these noxious
      agents has been ascribed to a number of factors constituting the gastric mucosal
      defense. These include mucus and bicarbonate secreted by surface epithelial
      cells, prostaglandins, sulfhydryl compounds and gastric mucosal blood flow. The
      latter is considered by several researchers to be of paramount importance in
      maintaining gastric mucosal integrity. The aim of this paper is to review the
      experimental and clinical data dealing with the role of mucosal blood flow and in
      particular the microcirculation in both damage and protection of the gastric
      mucosa.

PMID- 11595426
TI  - Functional and immunocytochemical evidence that galanin is a physiological
      regulator of human jejunal motility.
AB  - The neuropeptide galanin has species-dependent effects on intestinal motility. It
      has a contractile effect on rat jejunal muscle while it relaxes guinea-pig ileum
      by inhibiting cholinergic transmission. Its effect on human gut motility has been
      unknown. Extensive work led to the discovery of selective galanin analogues such
      as M15 [galanin(1-12)-Pro-substance-P(5-11)], M35 [galanin(1-12)-Pro-bradykinin(2
      9)-amide] that competitively inhibit various actions of galanin in the central
      nervous system. The present study was designed to examine the effect of galanin,
      M15 and M35 on longitudinal jejunal smooth muscle strips isolated from humans and
      rats, and to localize galanin-immunoreactivity in human jejunum. Galanin and ACh
      were equally effective in stimulating contractions of the isolated jejunal
      muscle: sigmoid curve fitting showed that maximal contractile response to galanin
      and ACh were 25.7+/-11.1 mN and 23.7+/-9.7 in humans, while 8.0+/-0.6 and 8.1+/
      0.3 mN in rats, respectively. These effects of galanin were not inhibited by
      either atropine (5 x 10(-6) M) or tetrodotoxin (3 x 10(-6) M). The potency of
      galanin inducing the contractile actions were similar in humans and rats.
      Interestingly, neither M15 nor M35 (up to 10(-7) M) were able to inhibit the
      responses of the smooth muscle to galanin. However, both putative galanin
      receptor antagonists showed agonist effects in our experimental models. In
      accordance with the functional studies, both the longitudinal and the circular
      muscle layers were abundant in nerve fibers and varicosities showing galanin
      immunoreactivity. Our data suggest that galanin is a potent physiological
      regulator of jejunal contractions in humans. Its action on the jejunum, however,
      is mediated by galanin receptors that are different from those located in the
      central nervous system.

PMID- 11595427
TI  - Endogenous bacteria-triggered inducible nitric oxide synthase activation protects
      the ovariectomized rat stomach.
AB  - Under experimental circumstances, ovariectomy attenuates gastric mucosal injury
      where nitric oxide (NO)-mediated pathways are involved. In this study, we have
      examined the changes in constitutive (cNOS) and inducible NO synthase (iNOS)
      enzyme activities (assessed by the citrulline assay), and the role of endogenous
      bacteria in ovariectomy-provoked mucosal defence. Gastric lesions were induced by
      indomethacin (50 mg/kg, s.c.) over a 4 h period in sham-operated and
      ovariectomized female Wistar rats. Groups of animals received the wide-spectrum
      antibiotic ampicillin (800 mg/kg/day, p.o., for 3 days), and others were injected
      with bacterial endotoxin (E. coli, 3 mg/kg, i.v., 5 h before autopsy). We found
      that ovariectomy increased iNOS and decreased cNOS activity (resulting an
      elevated total gastric NOS level), and protected the stomach, effects reversed by
      ampicillin treatment. In ovary-intact rats, administration of bacterial endotoxin
      enhanced gastric iNOS activity and reduced lesion-formation. These results
      suggest that ovariectomy improves gastric mucosal defence perhaps by endogenous
      bacteria-triggered induction of iNOS.

PMID- 11595428
TI  - Changes of salivary amylase in serum and parotid gland during pharmacological and
      physiological stimulation.
AB  - Although serum amylase level is an important diagnostic factor in certain
      salivary and pancreatic diseases, little information is available regarding the
      mechanism by which parotid amylase reaches the circulatory system. The present
      study was carried out to investigate the relationship between parotid isoamylase
      concentrations in blood serum and in parotid tissue in response to various
      stimuli. Wistar rats were fed with standard laboratory rodent chow; water was
      supplied ad libitum. In the first experiment, after a 16-h fasting, rats received
      either 5 mg/kg pilocarpine or saline (control). In the second study, after
      fasting, half of the rats were fed for 1 h, the other half received no food. In
      the third experiment, the changes in serum and tissue enzyme levels were
      monitored in freely fed animals during the peak-food intake phase, the first 2 h
      of the dark period. Amylase concentration was determined by using starch as a
      substrate. Pancreatic and parotid isoamylase levels in serum were separated by
      gel-electrophoresis utilizing differences in ionic properties of the isoenzymes.
      As expected, pilocarpine strongly stimulated tissue amylase discharge and serum
      amylase elevation. Similar, but less pronounced changes were observed not only
      during refeeding of fasted animals, but also in nonfasted rats during their peak
      feeding period. Our data suggest that pharmacological stimulation, such as with
      pilocarpine or feeding in fasted state, as well as a mild stimulation of parotid
      function by spontaneous food intake during nonfasted state results in a decrease
      in parotid tissue amylase activity and a proportional increase in serum levels of
      parotid isoamylase.

PMID- 11595429
TI  - Susceptibility of dopamine D5 receptor targeted mice to cysteamine.
AB  - BACKGROUND: Recently we demonstrated that gastric mucosa of rats can synthesize,
      store and release dopamine. Out of five different subtypes, mRNA of D5 (=D1b)
      dopamine receptor is very abundant in the gastric epithelium. D1 receptor
      selective dopamine agonists have been shown to protect against experimental
      gastro-duodenal lesions. AIMS: To test the hypothesis that protective effects of
      dopamine involve D5 receptors, mucosal lesions were induced in D5 receptor
      deficient (KO) and wild-type (WT) mice using cysteamine. Morphology and gastric
      acid secretion of D5 KO mice were also studied. METHODS: Single doses of 600
      mg/kg, 300 mg/kg cysteamine or vehicle were administered subcutaneously to fasted
      animals. After 24 h, number and severity of gastro-duodenal lesions were
      analyzed. Basal and histamine-induced maximal gastric acid output were measured
      by a stomach-sac wash-through method. RESULTS: All the KOs in the 600 mg/kg
      cysteamine group died within 4 h showing symptoms of toxicity while three out of
      four WTs survived (P<0.05). Mortality after 300 mg/kg cysteamine was
      significantly higher in KOs versus the WTs: 6/14 versus 2/11, P<0.05. Gastric
      lesion-index was also significantly higher in KOs (median, middle quartile): four
      (3-9) versus 0 (0-0), P<0.05. Duodenal lesions did not develop from this single
      dose of cysteamine in either genotype. Basal and histamine-induced maximal
      gastric acid output were comparable in the two genotypes. CONCLUSIONS: This study
      demonstrates that loss of D5 receptor causes mucosal vulnerability and increased
      toxicity of cysteamine in genetically manipulated mice. Thus, D5 receptor subtype
      is indeed likely to be involved in protective effects of dopamine in the stomach.

PMID- 11595430
TI  - Otilonium bromide enhances sensory thresholds of volume and pressure in patients
      with irritable bowel syndrome.
AB  - Visceral hyperalgesia has been suggested to play a role in the development of
      symptoms presented by irritable bowel syndrome patients. Otilonium bromide was
      developed to block smooth muscle Ca release to control cramping pain of these
      patients. AIMS: to determine whether otilonium bromide can influence sensory
      thresholds of patients suffering from irritable bowel syndrome. METHODS: 15
      patients with Rome-II positive IBS were tested by Synectics Visceral Stimulator
      Barostat using rapid phasic distension (870 ml/min). The sensory threshold for
      first sensation, stool, pain and maximum tolerable volume and pressure were
      measured. All of the parameters were tested before and 1 week after the
      initiation of otilonium bromide (Spasmomen, Berlin Chemie, 3x40 mg) therapy.
      RESULTS: The perceptual thresholds for first sensation, stool, pain and maximum
      tolerable distention were, 8.8+/-1.7 Hgmm, 19.2+/-2.1 Hgmm, 26.3+/-2.8 Hgmm,
      28.7+/-2.8 Hgmm for pressure, 90+/-21 ml, 145+/-28 ml, 208+/-25 ml, 213+/-28 ml
      for volume, before treatment, respectively. Otilonium bromide treatment did not
      influence the thresholds for first sensation and stool, 7.4+/-1.4 Hgmm, 20.7+/
      4.6 Hgmm and 83+/-21 ml, 178+/-35.8 ml, respectively. The pressure threshold of
      pain was significantly higher 1 week after treatment (26.3+/-2.8 Hgmm vs. 29.1+/
      5.5 Hgmm, P<0.05), but the volume threshold of this sensation remained unchanged
      (208+/-25 ml vs. 234+/-39 ml, not significant). The pressure (28.7+/-2.8 Hgmm vs.
      38.1+/-3.4 Hgmm, P<0.05) and volume (213+/-28 ml vs. 278+/-27 ml, P<0.05)
      thresholds for maximum tolerable volume were increased by 7 days otilonium
      bromide treatment. CONCLUSION: These data suggest that otilonium bromide enhances
      sensory thresholds to recto-sigmoideal distention.

PMID- 11595431
TI  - Prostaglandin E prevents indomethacin-induced gastric and intestinal damage
      through different EP receptor subtypes.
AB  - Gastrointestinal ulcerogenic effect of indomethacin is causally related with an
      endogenous prostaglandin (PG) deficiency, yet the detailed mechanism remains
      unknown. We examined the effect of various PGE analogues specific to EP receptor
      subtypes on these lesions in rats and mice, and investigated which EP receptor
      subtype is involved in the protective action of PGE(2). Fasted or non-fasted
      animals were given indomethacin s.c. at 35 mg/kg for induction of gastric lesions
      or 10-30 mg/kg for intestinal lesions, and they were killed 4 or 24 h later,
      respectively. Various EP agonists were given i.v. 10 min before indomethacin.
      Indomethacin caused hemorrhagic lesions in both the stomach and intestine. Prior
      administration of 16,16-dimethyl PGE(2) (dmPGE(2)) prevented the development of
      damage in both tissues, and the effect in the stomach was mimicked by 17-phenyl
      PGE2 (EP1), while that in the small intestine was reproduced by ONO-NT-012 (EP3)
      and ONO-AE-329 (EP4). Butaprost (EP2) did not have any effect on either gastric
      or intestinal lesions induced by indomethacin. Similar to the findings in rats,
      indomethacin caused gastric and intestinal lesions in both wild-type and knockout
      mice lacking EP1 or EP3 receptors. However, the protective action of dmPGE(2) in
      the stomach was observed in wild-type and EP3 receptor knockout mice but not in
      mice lacking EP1 receptors, while that in the intestine was observed in EP1
      knockout as well as wild-type mice but not in the animals lacking EP3 receptors.
      These results suggest that indomethacin produced damage in the stomach and
      intestine in a PGE(2)-sensitive manner, and exogenous PGE(2) prevents gastric and
      intestinal ulcerogenic response to indomethacin through different EP receptor
      subtypes; the protection in the stomach is mediated by EP1 receptors, while that
      in the intestine mediated by EP3/EP4 receptors.

PMID- 11595432
TI  - Bicarbonate stimulatory action of nizatidine, a histamine H(2)-receptor
      antagonist, in rat duodenums.
AB  - Nizatidine, a histamine H(2)-antagonist, is known to inhibit acetylcholinesterase
      (AChE) activity and is used clinically as a gastroprokinetic agent as well as the
      anti-ulcer agent. We examined whether or not nizatidine stimulates duodenal
      HCO(3)(-) secretion in rats through vagal-cholinergic mechanisms by inhibiting
      AChE activity. Under pentobarbital anesthesia, a proximal duodenal loop was
      perfused with saline, and the HCO(3)(-) secretion was measured at pH 7.0 using a
      pH-stat method and by adding 10 mM HCl. Nizatidine, neostigmine, carbachol,
      famotidine or ranitidine was administered i.v. as a single injection. Intravenous
      administration of nizatidine (3-30 mg/kg) dose-dependently increased the HCO(3)(
      ) secretion, and the effect at 10 mg/kg was equivalent to that obtained by
      carbachol at 0.01 mg/kg. The HCO(3)(-) stimulatory action of nizatidine was
      observed at the doses that inhibited the histamine-induced acid secretion and
      enhanced gastric motility. This effect was mimicked by neostigmine (0.03 mg/kg)
      and significantly attenuated by bilateral vagotomy and pretreatment with atropine
      but not indomethacin. The IC(50) of nizatidine for AChE of rat erythrocytes was
      1.4 x 10(-6) M, about 12 times higher than that of neostigmine. Ranitidine showed
      the anti-AchE activity and increased duodenal HCO(3)(-) secretion, similar to
      nizatidine, whereas famotidine had any influence on neither AChE activity nor the
      HCO(3)(-) secretion. On the other hand, duodenal damage induced by acid perfusion
      (100 mM HCl for 4 h) in the presence of indomethacin was significantly prevented
      by nizatidine and neostigmine, at the doses that increased the HCO(3)(-)
      secretion. These results suggest that nizatidine increases HCO(3)(-) secretion in
      the rat duodenum, mediated by vagal-cholinergic mechanism, the action being
      associated with the anti-AChE activity of this agent.

PMID- 11595433
TI  - Gastric mucosal endogenous prostacyclin levels are different in Brattleboro rats
      compared with Wistar strain.
AB  - Homozygous Brattleboro rats were investigated and compared to normal
      (physiological) Wistar strain rats regarding their gastric mucosal endogenous
      prostacyclin (PG-I(2)) level. It seems that the Brattleboro animals have a
      significantly lower level of this important protective material. Wistar rats
      having an artificial pituitary stalk lesion (which is the artificial equivalent
      of homozygous Brattleboro animals) showed no differences in endogenous mucosal
      prostacyclin level compared to normal Wistar rats. Therefore, we concluded that
      this hitherto unknown property of the homozygous Brattleboro rats is genetically
      determined.

PMID- 11595434
TI  - Further analysis of prostacyclin's effect on rat gastric mucosal nucleic acid
      content.
AB  - Graded single and multiple oral doses of prostacyclin enhance, in a direct dose
      dependent manner, the DNA and RNA content of rat gastric (antral and fundic)
      mucosa, resulting in a decreased RNA/DNA ratio. This latter phenomenon is a
      convincing sign of new cell formation. The arithmetical (theory of functions)
      analysis of the data resulted in equations, defined mathematically, of
      prostacyclin's dose-dependent effect.

PMID- 11595435
TI  - Capsaicin-sensitive afferents and their role in gastroprotection: an update.
AB  - The pivotal role of capsaicin-sensitive peptidergic sensory fibers in the
      maintenance of gastric mucosal integrity against injurious interventions was
      suggested by the authors 20 years ago. Since then substantial evidence has
      accumulated for the local sensory-efferent function of the released CGRP,
      tachykinins and NO in this gastroprotective mechanism. This overview outlines
      some recent achievements which shed light on new aspects and further horizons in
      this field. (1) Cloning the capsaicin VR-1 receptor (an ion channel-coupled
      receptor) and raising the VR-1 knockout mice provided a definite molecular
      background for the existence of capsaicin-sensitive afferents with both sensory
      and mediator releasing functions in the stomach. This cation channel is also
      sensitive to hydrogen ions. (2) VR-1 agonists (capsaicin, resiniferatoxin,
      piperine) protect against gastric ulcer of the rat parallel with their sensory
      stimulating potencies. (3) Antidromic stimulation of capsaicin-sensitive vagal
      and somatic afferents results in the release of CGRP, tachykinins, NO and
      somatostatin. Somatostatin with gastroprotective effect is released from D cells
      and sensory nerve endings. (4) The recent theory for the existence of spinal
      afferents without sensory function [P. Holzer, C.A. Maggi, Dissociation of dorsal
      root ganglion neurons into afferent and efferent-like neurons, Neuroscience 86
      (1998) 389-398] is discussed. Data proposed to support this theory are
      interpreted here on the basis of a dual sensory-efferent function of VR-1
      positive afferents, characterized by a frequency optimum of discharges for
      release vasodilatory neuropeptides below the nociceptive threshold. (5) Recent
      data on the effect of capsaicin in healthy human stomach are summarized. These
      results indicate that the gastroprotective effect of capsaicin in the human
      stomach involves additional mechanisms to those already revealed in the rat.

PMID- 11595436
TI  - Activation of central opioid receptors may induce gastric mucosal defence in the
      rat.
AB  - The effect of different opioid peptides on acidified ethanol- and indomethacin
      induced gastric mucosal lesions was studied following intracerebroventricular
      (i.c.v.) administration. It was found that both the selective delta opioid
      receptor agonists--deltorphin II, [D-Ala(2), D-Leu(5)]-enkephalin (DADLE), [D
      Pen(2), D-Pen(5)]-enkephalin (DPDPE)-, mu-opioid receptor agonist--[D-Ala(2),
      Phe(4), GlyT-ol]-enkephalin (DAGO)--as well as beta-endorphin inhibited the
      mucosal damage induced by both ethanol and indomethacin in pmolar dose range. In
      contrast, the gastric acid secretion was not influenced by DADLE in the dose of
      16 nmol/rat and only a slight reduction (40%) was induced by DAGO in the dose of
      1.9 nmol/rat. The protective effect was abolished in both ulcer models by
      bilateral cervical vagotomy. N(G)-nitro-L-arginine, an inhibitor of NO synthase,
      reduced the protective action in ethanol-induced, but not in indomethacin-induced
      gastric damage. The results suggest that activation of supraspinal delta and mu
      opioid receptors resulted in inhibition of gastric mucosal lesions elicited by
      ethanol or indomethacin. The gastroprotective action is independent from the
      effect of opioids on acid secretion. Vagal nerve is involved in conveying the
      central action to the periphery. The mechanism of the gastroprotective effect of
      opioids is different in ethanol- and indomethacin-ulcer models: prostaglandins
      and nitric oxide are likely to be involved in the protective action of opioid
      peptides in ethanol-, but not in the indomethacin-ulcer model.

PMID- 11595437
TI  - Failure of capsaicin-containing red pepper sauce suspension to induce esophageal
      motility response in patients with Barrett's esophagus.
AB  - The physiologic importance of afferent sensory pathways in the esophageal motor
      functions has been recently recognised. Capsaicin-sensitive sensory afferents
      were shown to play a role in the maintenance of mucosal integrity of the GI
      tract, and regulation of human esophageal motility. The aim of this study was to
      investigate the effect of topical application of capsaicin-containing red pepper
      sauce (Tabasco, 25%v/v, pH:7.0) suspension on the phasic activity of the human
      esophagus of healthy volunteers and patients with Barrett's esophagus. METHODS:
      The diagnosis of Barrett's esophagus was based on the findings of esophagoscopy
      and histology taken from the squamocolumnar junction of the esophagus. Esophageal
      motility was measured by perfusion manometry before and after application of red
      pepper sauce. RESULTS: Capsaicin containing red pepper sauce increases the
      motility response (LES tone, contraction amplitude, propagation velocity) of the
      human esophagus in healthy volunteers. This response failed in patients with
      Barrett's esophagus. CONCLUSION: Impaired esophageal sensory motor function may
      serve as one etiologic role in the development of Barrett's esophagus.

PMID- 11595439
TI  - Involvement of the opioid system in the central antisecretory action of alpha-2
      adrenoceptor agonists in rat.
AB  - The aim of the present study was to analyse the role of the central alpha-2
      adrenoceptors in the regulation of gastric acid secretion in pylorus ligated
      rats. It was found that the intracerebroventricularly (icv.) injected presynaptic
      alpha-2 adrenoceptor agonist clonidine and the alpha-2A adrenoceptor subtype
      selective stimulant oxymetazoline exerted a dose dependent inhibition on gastric
      acid secretion. The antisecretory ED(50) values for clonidine and oxymetazoline
      were 20 and 7.5 nmol/rat icv., respectively. The antisecretory effect of these
      compounds was antagonised by the presynaptic adrenoceptor antagonist yohimbine
      (50 nmol/rat icv.) indicating that the action is mediated through central
      presynaptic alpha-2 adrenoceptors. Moreover, naloxone (50 nmol/rat icv.)--non
      selective opioid antagonist--and naltrindole (0.5 nmol/rat icv.)--delta-opioid
      receptor selective antagonist--also decreased the antisecretory effect of
      clonidine and oxymetazoline suggesting that the endogenous opioid system is
      likely to be involved in the central antisecretory action of alpha-2 adrenoceptor
      stimulants.

PMID- 11595438
TI  - Gastroprotective action of glucocorticoids during the formation and the healing
      of indomethacin-induced gastric erosions in rats.
AB  - The aim of the present study consisted of the investigation of glucocorticoid
      role in the formation and the healing of indomethacin-induced (25 mg/kg, s.c.)
      gastric erosions in rats. The effect of deficiency of glucocorticoid production
      followed by corticosterone replacement on the formation and the healing of the
      gastric erosions was evaluated. Glucocorticoid production was decreased by
      adrenalectomy or by delayed inhibitory action after a single pharmacological dose
      of cortisol (300 mg/kg i.p.) injected 1 week before the onset of ulcerogenic
      stimulus. Indomethacin induced corticosterone rise and caused gastric erosions.
      The loss of indomethacin-induced plasma corticosterone rise potentiated the
      formation of indomethacin-induced erosions in both models. The area of gastric
      erosions in rats with glucocorticoid deficiency was considerably larger than that
      in control animals 4 h after indomethacin administration as well as during 48 h
      after the drug administration (period of erosion healing). Injecting
      corticosterone in rats with glucocorticoid deficiency significantly decreased the
      formation of indomethacin-induced gastric erosions and promoted their healing.
      Thus, the present data support the gastroprotective action of glucocorticoids in
      the formation and in the healing of indomethacin-induced mucosal injury.

PMID- 11595440
TI  - Neonatal monosodium glutamate treatment abolishes both delta opioid receptor
      induced and alpha-2 adrenoceptor-mediated gastroprotection in the lower brainstem
      in rats.
AB  - Neonatal monosodium glutamate treatment reduced immunoreactive beta-endorphin
      content in the mediobasal hypothalamus by 50% in adult, male Wistar rats as
      compared to hypertonic saline-treated littermates; there was also a moderate
      (approx. 25%) reduction in the rostral part of the nucleus of the solitary tract.
      In sham-treated adults the intracisternally injected alpha-2 adenoceptor
      stimulant clonidine (0.47 nmol/rat) and the delta opioid receptor type agonist (D
      Ala(2), D-Leu(5))-enkephalin (0.8 nmol/rat) reduced acidified ethanol-induced
      mucosal lesions in the stomach by 84.1 and 77.5%, respectively, whereas the same
      doses were completely ineffective in rats treated neonatally by monosodium
      glutamate. The data taken together with the results of previous studies with the
      same substances in rats with retroarcuate knife cuts suggest that neuronal damage
      in the nucleus of the solitary tract region rather than in the arcuate nucleus is
      responsible for the changes seen in the pharmacological responsiveness.

PMID- 11595441
TI  - Pharmacological analysis of wine-stimulated gastric acid secretion in dogs.
AB  - Wine apparently stimulates gastric acid secretion both in man and animals, yet
      the underlying mechanism remains unclear. The present study was attempted to
      clarify the pharmacological properties involved in gastric acid secretion
      stimulated by wine in beagle dogs. Commercially available red or white wine, 14%
      ethanol, or 10% peptone meal was intragastrically administered to dogs with
      vagally denervated Heidenhain pouches. Gastric acid secretion was stimulated by
      both red and white wines (25-50 ml) for 45-60 min. While S-0509 only tended to
      inhibit wine-stimulated gastric acid secretion, both atropine and famotidine
      significantly inhibited wine-stimulated gastric acid secretion. Plasma gastrin
      level was not significantly increased by administration of red and white wines.
      Administration of 14% ethanol also stimulated gastric acid secretion, but the
      effect was about half of that of wine. Combined administration of wine and
      peptone resulted in a biphasic stimulation of gastric acid secretion. S-0509,
      atropine and famotidine significantly inhibited wine+peptone meal stimulation,
      yet the order of inhibition of cumulative acid secretion was in the order,
      famotidine>atropine>S-0509. It was concluded that wine stimulated gastric acid
      secretion in denervated dogs via acethylcholine- and histamine-dependent
      mechanisms, but nearly independent from the intervention of gastrin.

PMID- 11595442
TI  - The key-role of vagal nerve and adrenals in the cytoprotection and general
      gastric mucosal integrity.
AB  - BACKGROUND: Our laboratory group observed earlier that the gastric mucosal
      cytoprotective effect of prostacyclin (PGI(2)) disappeared after surgical
      vagotomy in rats. Similarly to this, the beta-carotene induced gastric
      cytoprotection disappeared in adrenalectomized rats too. AIMS: In these studies
      we aimed to investigate the possible role of vagal nerve and adrenals in the
      development of gastric mucosal lesions induced by exogenously administered
      chemicals (ethanol, HCl, NaOH, NaCl and indomethacin), and on the effects of
      cytoprotective and antisecretory drugs (atropine, cimetidine), and scavengers
      (vitamin A and beta-carotene). METHODS: The observations were carried out in
      fasted CFY strain rats. The gastric mucosal lesions were produced by intragastric
      (i.g.) administration of narcotising agents (96% ethanol; 0.6 M HCl; 0.2 M NaOH;
      25% NaCl) or subcutaneously (s.c.) administered indomethacin (20 mg/kg) in
      intact, surgically bilaterally vagatomized, and adrenalectomized rats without or
      with glucocorticoid supplementation (Oradexon, 0.6 mg/kg given i.m. for 1 week).
      The gastric mucosal protective effect of antisecretory doses of atropine (0.1-0.5
      1.0 mg/kg i.g.) and cimetidine (10-25-50 mg/kg i.g.), and vitamin A and beta
      carotene (0.01-0.1-1.0-10 mg/kg i.g.) was studied. The number and severity of
      mucosal gastric lesions was numerically or semiquantitatively measured. In other
      series of observations the gastric acid secretion and mucosal damage were studied
      in 24 h pylorus-ligated rats without and with acute bilateral surgical vagotomy.
      RESULTS: It was found that: (1) the chemical-induced gastric mucosal damage was
      enhanced in vagotomized and adrenalectomized rats, meanwhile the endogenous
      secretion of gastric acid, and the development of mucosal damage can be prevented
      by surgical vagotomy; (2) the gastric cyto- and general protection produced by
      the drugs and scavengers disappeared in vagotomized and adrenalectomized rats;
      (3) the gastric mucosal protective effects of drugs and of scavengers returned
      after sufficient glucocorticoid supplementation of the rats. CONCLUSION: It has
      been concluded that the intact vagal nerve and adrenals have a key role in the
      gastric mucosal integrity, and in drugs- and scavengers-induced gastric cyto- and
      general mucosal protection.

PMID- 11595443
TI  - Changes of serum carotenoids in patients with esophageal, gastric,
      hepatocellular, pancreatic and colorectal cancer.
AB  - The serum levels of carotenoids (vitamin A, lutein, zeaxanthin, alfa- and beta
      cryptoxanthin, alfa- and beta-carotene) were measured in healthy persons (n=40)
      and in 98 patients with different malignant gastrointestinal diseases (44
      patients with colon adenocarcinoma, 21 with gastric cancer, 15 with
      hepatocellular adenocarcinoma, 10 patients with pancreas adenocarcinoma and eight
      patients with esophagus cancer). The serum levels of carotenoids were measured
      with high-pressure liquid chromatography. The sera of the patients were taken at
      the time of the diagnosis. RESULTS: the measurements indicated that (1) the serum
      level of vitamin A and zeaxanthin were significantly lower in all of these groups
      (except of pancreas adenocarcinoma), but the extent of the A decrease was
      different in the patients with different types of gastrointestinal malignancy.
      The serum level of vitamin A was in the healthy subjects 2.072+/-0.332 mmol/l and
      in the case of gastrointestinal malignancies was 0.77+/-0.14 mmol/l (P<0.001) The
      serum level of zeaxanthin was in the healthy subjects 0.143+/-0.057 mmol/l and at
      the malignancies was 0.042+/-0.014 mmol/l (P<0.01). (2) There were no significant
      differences in the serum levels of other carotenoids in the checked groups. (3)
      The serum level of cholesterol, total protein, albumin and haemoglobin were in
      the normal range in these patients. These results indicate that the carotenoids
      may be responsible nutritional factors (as nutritional scavengers) in the
      development of different malignant diseases. This supposed role in the
      carcinogenesis does not depend fully on the vitamin A activity.

PMID- 11595444
TI  - On a possible new intracellular signal-system in rat gastric mucosa.
AB  - It is known that cAMP and cGMP, as an "intracellular second messenger system"
      play a significant role as a signal system, in the mechanism of action of anti
      ulcerogenic (cytoprotective) drugs. According to our present, preliminary
      investigations it seems that during different experimental circumstances the
      gastric mucosal 3'-5'-cyclic-cytidine-mono-phosphate (cCMP) 3'-5'-cyclic-uridine
      monophosphate and (cUMP) levels were changed--similarly to CAMP and cGMP--and
      these changes might be a possible indicator of a further, most probably
      secondary, signal- system role.

PMID- 11595445
TI  - Comparative study between the free radicals and tumor markers in patients with
      gastrointestinal tumors.
AB  - The tumorous processes, increased level of tumor markers and the change of free
      radical status are associated in patents with gastrointestinal tumors. The aim of
      this study was to examine free radical status and tumor markers in patients with
      gastrointestinal tumors. Two hundered and thirteen patients with gastrointestinal
      tumor were examined. In the control group 44 non-tumorous patients were examined.
      The tumor markers (CEA, CA 19-9, CA 72-4, AFP, TPA, AGP) and free radical status
      (total scavenger capacity) were diagnosed using venal blood (obtained by LIA-kits
      and chemiluminescent methods, LIA-mAT and the Lumat Berthold instrument). It has
      been found that: (1) The results showed that the tumor markers, TPA and AGP are
      the best indicators for the tumorous process; (2) The AGP serum level was in the
      operable case 91.56+/-38.29 mg/dl meanwhile its value was, 128.46+/-47.62 mg/dl
      (P<0.001) in the inoperable case; and (3) The TPA value was 118.37+/-155.47 mg/dl
      in the operable case, (P<0.001) while its value was 227.32+/-244.39 mg/dl in
      inoperable cases. The significantly high levels of the plasma Chemiluminescent
      Light Intensity (CLI)=28.12+/-25.96; was obtained in patients with rectal tumors
      vs. in the control cases CLI= 4.27+/-5.12 RLU% (Relative Light Unit; mean+S.D.;
      P<0.005). In six of these cases, the free radical status examination indicated
      the presence of the tumor, even though the level of tumor markers was normal. It
      has been concluded that the testing of both regular tumor markers and free
      radical status has an important role in the diagnosis and monitoring of the
      patients with gastrointestinal tumors.

PMID- 11595446
TI  - Current roles of nitric oxide in gastrointestinal disorders.
AB  - It has been confusing as to what roles nitric oxide (NO) has in different
      physiological and pathological mechanisms in various diseases. In the
      gastrointestinal tract, NO can be either protective or deleterious in different
      disorders. This depends on what type of nitric oxide synthase (NOS) is involved
      in these pathological conditions. Constitutive NOS (cNOS) is responsible for
      production of NO in physiological context. In contrast, inducible NOS (iNOS)
      produces NO in pathophysiological circumstances. NO is implicated in mechanisms
      maintaining the integrity of the gastric epithelium. In this connection, it
      regulates gastric blood flow and directly stimulates gastric mucus secretion by
      activating soluble guanylate cyclase. A blockade of NO production resulted in an
      impairment of the vascular response and the subsequent alkaline flux in the
      lumen. This would impair the restitution process. Endogenous NO also contributes
      to the inhibition of acid secretion in the stomach. Indeed the adverse action of
      cigarette smoking on ulcer healing is largely dependent on the deficiency of cNOS
      and a subsequent depression of gastric blood flow and angiogenesis. To this end,
      NO may act as a crucial signal to promote endothelial cell differentiation into
      vascular tubes. In experimental colitis, NO derived from iNOS, together with
      other free radicals contribute significantly to the inflammatory response in the
      colon. It is also involved in the ulcerogenic effect of passive smoking on
      colitis. The mechanism is likely mediated through the interaction with superoxide
      to produce peroxynitrite, a strong oxidizing agent that initiates lipid
      peroxidation. In conclusion, NO in low concentration derived from cNOS is
      cytoprotective by directly acting as an inducer of defense responses in the
      gastrointestinal tract. However, higher concentrations of NO from iNOS exhibit
      toxic effects through nitrosative and oxidative stress.

PMID- 11595447
TI  - Helicobacter pylori lipopolysaccharide provokes iNOS-mediated acute systemic
      microvascular inflammatory responses in rat cardiac, hepatic, renal and pulmonary
      tissues.
AB  - We have examined the effects of intravenous administration of a purified
      lipopolysaccharide (LPS) from Helicobacter pylori (3 mg kg(-1), i.v.) on rat
      vascular permeability, assessed by the radiolabelled human serum albumin leakage
      technique in the heart, kidney, liver and lung 4 h after challenge. An increased
      vascular permeability in cardiac, renal, hepatic and pulmonary tissues after
      challenge was determined. The albumin leakage observed in all these organs could
      be prevented by the selective inducible nitric oxide synthase inhibitor, N-(8
      (aminomethyl)benzyl)-acetamidine (1400W; 0.2-1 mg kg(-1), s.c.) administered
      concurrently with LPS. Thus, H. pylori LPS can provoke a microvascular
      inflammatory response in the rat cardiac, renal, hepatic and pulmonary tissues,
      actions mediated through the activation of the inducible nitric oxide synthase
      isoenzyme.

PMID- 11595448
TI  - Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric
      pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole,
      sulphasalazine and methylprednisolone.
AB  - Recently, we showed cysteamine-duodenal lesions without gastric acid, since they
      were induced also in gastrectomized rats, as in naive rats, and they were
      inhibited by the novel stomach pentadecapeptide BPC 157 as well as standard
      antiulcer drugs (i.e. cimetidine, ranitidine, omeprazole, bromocriptine,
      atropine). Therefore, as an advantage of considering cysteamine as a directly
      acting cytotoxic agent and mentioned agents as direct cytoprotective agents, the
      present focus was on the ulcerogenic effect of cysteamine and protective effect
      of gastroduodenal antiulcer agents outside upper gastrointestinal tract (i.e. in
      colon). Intrarectal administration of the cysteamine (200 or 400 mg/kg b.w)
      produced severe colon lesions (i.e. transmural inflammation with serosal
      involvement) in rats (30 min-72 h-experimental period), apparently distinctive
      from smaller lesions after non-specific irritant enema [diluted HCl solution, pH
      3.8 (adjusted to pH of cysteamine solution (pH 3.8)]. All of the tested antiulcer
      agents were applied simultaneously with cysteamine enema (8 cm from the anus, in
      a volume of the 1.0 ml/rat) intraperitoneally (i.p.), intragastrically (i.g.) or
      intrarectally (i.r.). Pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w.),
      given in either regimen, previously shown to have, besides others, a particular
      beneficial activity just in the intestinal mucosa, inhibited these cysteamine
      colon lesions (assessed after 30 min, 60 min, 180 min, 24 h, 48 h, 72 h following
      cysteamine in a dose of either 200 or 400 mg/kg i.r.). Cysteamine-colon lesions
      were also attenuated by standard antiulcer agents (mg/kg b.w.), given i.p., i.g.,
      or i.r., such as ranitidine (10), cimetidine (50), omeprazole (10), atropine
      (10), together with methylprednisolone (1), and sulphasalazine (50, i.r.),
      assessed 30 min following application of 200 mg of cysteamine. Finally, standard
      cysteamine duodenal lesions (assessed 24 h after a subcutaneous application of
      400 mg/kg of cysteamine) were also attenuated by these agents application (given
      in the same doses, i.p., 1 h before cysteamine), with only exception to
      sulphasalazine. Thus, the extended cysteamine specific ulcerogenic effect,
      cysteamine colon/duodenum lesion-link and an extenuation of agents protection
      from upper to lower part of gastrointestinal tract (i.e. stomach pentadecapeptide
      BPC 157, standard antiulcer agents, cimetidine, ranitidine, atropine, omeprazole)
      and vice versa (remedies for inflammatory bowel disease) evidenced in the present
      study may be potentially important for both further experimental and clinical
      research.

PMID- 11595449
TI  - Active water selective channels in the stomach: investigation of aquaporins after
      ethanol and capsaicin treatment in rats.
AB  - Recent studies discovered the existence of aquaporins (AQP), suggesting their
      roles in the active, ATP dependent water secretion or absorption. Our recent
      development of the monoclonal antibody family against aquaporins (Type 1 and 4)
      allowed us a good opportunity to investigate the mechanism of the gastric mucosal
      edema in a rat model. THE AIM OF OUR STUDY was to evaluate the changes in the
      tissue level of aquaporins (AQP1 and AQP4) after ethanol and capsaicin treatment
      in rat stomach. MATERIALS AND METHODS: the experiments were carried out on
      Sprague-Dawley rats weighing 150-200 g. The animals were fasted for 24 h, after
      the 1 ml of ethanol (50% v/v) or capsaicin (2 mg/ml) was given intragastrically.
      Rats were sacrificed after 5, 30, 60, 120 and 240 min, the tissue level of AQP1
      and AQP4 was investigated immunoserologically by ELISA and dot-blot methods using
      our monoclonal antibodies. The location of these aquaporins in the gastric tissue
      was demonstrated by immunohistochemistry. RESULTS: (1) in ethanol-treated
      stomach, both AQP1 and AQP4 increased after 5 min simultaneously with gastritis,
      then decreased dramatically depending on time. (2) In the capsaicin-treated group
      there were no changes in the tissue level of aquaporins in the first hour. After
      60 min both AQP1 and AQP4 increased in the stomach without any macroscopically
      detectable changes, then decreased depending on time. (3) The immunohistochemical
      investigations using our monoclonal antibodies seem to support our present
      quantitative results. CONCLUSION: chemically induced gastric mucosal lesions are
      started by an extended edema. In the induction of the edema and the subsequent
      gastric injury, aquaporins (both AQP1 and AQP4) play an important role in the
      maintenance of mucosal integrity.

PMID- 11595450
TI  - Cytoprotective effects of met-enkephalin and alpha-MSH on ethanol induced gastric
      lesions in rats.
AB  - We used the rat model of ethanol induced gastric lesions to measure
      cytoprotective effects of neuropeptides met-enkephalin and alpha-melanocyte
      stimulating hormone (alpha-MSH). The lesions were induced with i.g. application
      of 1 ml 96% ethanol. The peptides were given i.p. 1 h before the ethanol.
      Sacrifice was made 1 h after ethanol application and hemorrhagic gastric area was
      assessed in mm(2). alpha-MSH and met-enkephalin exhibited significant and
      additive cytoprotective effects. The protective effects of alpha-MSH were
      significantly stronger than of met-enkephalin. Almost total absence of lesions
      was obtained with met-enkephalin and alpha-MSH mixture 10:1 (10 mg/kg met
      enkephalin and 1 mg/kg alpha-MSH). The addition of indomethacin (5 mg/kg s.c.)
      almost completely abolished the effect of met-enkaphalin, while alpha-MSH
      mediated cytoprotection was weakened but still present. Interestingly,
      indomethacin also blocked almost completely the cytoprotective effects of met
      enkephalin and alpha-MSH mixture. The latter result may have a practical
      consequence for the clinical trials in which met-enkephalin and alpha-MSH could
      be used in combination with non-steroidal anti-inflammatory drugs.

PMID- 11595451
TI  - Therapy effect of antiulcer agents on new chronic cysteamine colon lesion in rat.
AB  - After demonstration that cysteamine induced duodenal lesions in gastrectomized
      rats, while a number of antiulcer drugs mitigated these lesions, it was shown
      that one single intrarectal (i.r.) cysteamine application produced severe colon
      lesions in acute studies in rats. Thus, the further focus was on the protracted
      effect of cysteamine challenge (400 mg/kg b.w. i.r.) and therapy influence in
      chronic experiments in female rats. Regularly, cysteamine colon lesions were
      markedly mitigated by ranitidine (10), omeprazole (10), atropine (10),
      methylprednisolone (1), sulphasalazine (50; mg/kg), pentadecapeptide BPC 157 (PL
      10, PLD-116; 10 microg or 10 ng/kg). Specifically, after 1 or 3 months following
      initial challenge (cysteamine 400 mg/kg i.r.) in female rat, the therapy [BPC 157
      (PL-10, PLD-116 (10.0 microg or 10.0 ng/kg; i.g., i.p., i.r.), ranitidine,
      omeprazole, atropine, methylprednisolone, sulphasalazine (i.p.)] reversed the
      protracted cysteamine colon injury: the 1 week-regimen (once daily application)
      started after 1 month post-cysteamine, as well as the 2 weeks-regimen (once daily
      application), which started after 3 months. The effect on recidive lesion was
      also tested. These cysteamine lesions may reappear after stopping therapy (after
      stopping therapy for 3 weeks at the end of 2-weeks regimen started in 3 months
      cysteamine female rats) in sulphasalazine group, while this reappearance is
      markedly antagonized in pentadecapeptide BPC 157 (PL-10, PLD-116)-rats
      (cysteamine-colon lesion still substantially low).

PMID- 11595452
TI  - Ethanol gastric lesion aggravated by lung injury in rat. Therapy effect of
      antiulcer agents.
AB  - Hemorrhagic mucosal lesions in the stomach in the rat induced by an
      intragastrical application of 1 ml of 50 or 75% ethanol were aggravated by
      preceding lung damage provoked by an intratracheal instillation of pyrogen-free
      saline or HCl (pH 1.75) or 50-h exposure to 100% oxygen. Due to the particular
      preceding aggravating circumstances, these lesions were taken to be of a special
      kind, rather than ordinary. So far, it is not known whether and how antiulcer
      agents may influence these lesions. Rats received an intratracheal (i.t.) HCl
      instillation [1.5 ml/kg HCl (pH 1.75)] (lung-lesion), and an intragastric
      instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl
      instillation), and were sacrificed 1 h after ethanol. Basically, in lung injured
      rats, the subsequent ethanol-gastric lesion was markedly aggravated. This
      aggravation, however, in turn, did not affect the severity of the lung lesions in
      the further period, at least for a 1-h observation. Taking intratracheal HCl
      instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419,
      coded BPC 157 (PL-10, PLD-116; 10 microg, 10 ng, 10 pg), ranitidine (10 mg),
      atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)]
      (1) once, only prophylactically [as a pre-treatment (at -1 h), or as a co
      treatment (at 0)], or only therapeutically (at +18 h or +24 h); (2) repeatedly,
      combining prophylactic/therapeutic regimens [(-1 h)+(+24 h) or (0)+(+24 h)], or
      therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. In general, the antiulcer
      agents did protect against ethanol gastric lesions regardless of the presence of
      the severe lung injury, in all of the used regimens. Of note, combining their
      prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) may increase
      the antiulcer potential, and the effect that had been not seen already with
      single application, became prominent after repeated treatment.

PMID- 11595453
TI  - Chronic cytoprotection: pentadecapeptide BPC 157, ranitidine and propranolol
      prevent, attenuate and reverse the gastric lesions appearance in chronic alcohol
      drinking rats.
AB  - Unlike severe gastric damage acutely induced by ethanol administration in rat,
      the ulcerogenic effect of chronic alcohol administration (3.03 g/kg b.w. or 7.28
      g/kg b.w.) given in drinking water, producing liver lesions and portal
      hypertension, is far less investigated. Therefore, focus was on the antiulcer
      effect of the gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known
      to have a beneficial effect in variety of gastrointestinal lesions models (10
      microg or 10 ng/kg b.w. i.p. or i.g.), ranitidine (10 mg/kg b.w. i.g.) and
      propranol (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.; control). They
      were given once daily (1) throughout 10 days preceding alcohol consumption, (2)
      since beginning of alcohol drinking till the end of the study, (3) throughout the
      last month of alcohol consumption, 2 months after alcohol drinking had been
      initiated. Gastric lesions were assessed, at the end of 3 months drinking [(1),
      (2)] or with respect to therapeutic effect of medication before medication or at
      the end of therapy. Pentadecapeptide BPC 157, ranitidine and propranolol may
      prevent gastric lesion development if given prophylactically, before alcohol
      drinking. Likewise, they attenuate the lesion appearance given once daily
      throughout the drinking period. Importantly, when given therapeutically, they may
      antagonize otherwise pertinent lesion presence in stomach mucosa of the drinking
      rats. Thus, these results demonstrate that pentadecapeptide BPC 157, ranitidine
      and propranol may prevent, attenuate or reverse the gastric lesions appearance in
      chronically alcohol drinking rats, and may be used for further therapy, while the
      other studies showed that their effect (except to ranitidine) is parallel with
      their beneficial effect on liver lesion and portal hypertension.

PMID- 11595454
TI  - Lung lesions and anti-ulcer agents beneficial effect: anti-ulcer agents
      pentadecapeptide BPC 157, ranitidine, omeprazole and atropine ameliorate lung
      lesion in rats.
AB  - Anti-ulcer agents may likely attenuate lesions outside the gastrointestinal
      tract, since they had protected gastrectomized rats (a "direct cytoprotective
      effect"). Therefore, their therapeutic potential in lung/stomach lesions were
      shown. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH
      1.75)] (lung lesion), and an intragastric (i.g.) instillation of 96% ethanol
      (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), then sacrificed 1 h
      after ethanol. Basically, in lung-injured rats, the subsequent ethanol-gastric
      lesion was markedly aggravated. This aggravation, however, in turn, did not
      affect the severity of the lung lesions in the further period, at least for 1 h
      of observation. Taking intratracheal HCl-instillation as time 0, a gastric
      pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (10 microg, 10 ng, 10
      pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg,
      intraperitoneally (i.p.)] (i) once, only prophylactically [as a pre-treatment (at
      -1h)], or as a co-treatment [at 0)], or only therapeutically (at +18h or +24 h);
      (ii) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h)] or
      [(0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. For all
      agents, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at
      0/+24 h) attenuated lung lesions; even if effect had been not seen already with a
      single application, it became prominent after repeated treatment. In single
      application studies, relative to controls, a co-treatment (except to omeprazole),
      a pre-treatment (at -1 h) (pentadecapeptide BPC 157 and atropine, but not
      ranitidine and omeprazole) regularly attenuated, while therapeutically, atropine
      (at +18 h), pentadecapeptide BPC 157 highest dose and omeprazole (at +24 h),
      reversed the otherwise more severe lung lesions.

PMID- 11595455
TI  - Phytohaemagglutinin inhibits gastric acid but not pepsin secretion in conscious
      rats.
AB  - Phytohaemagglutinin (PHA), a kidney bean lectin, is known for its binding
      capability to the small intestinal surface. There has been no data available,
      however, on the biological activity of PHA in the stomach. Recent observations
      indicate that PHA is able to attach to gastric mucosal and parietal cells.
      Therefore, we examined whether PHA affects gastric acid and pepsin secretion in
      rats. Rats were surgically prepared with chronic stainless steel gastric cannula
      and with indwelling polyethylene jugular vein catheter. During experiments,
      animals were slightly restrained. Gastric acid secretion was collected in 30 min
      periods. Acid secretion was determined by titration of the collected gastric
      juice with 0.02 N NaOH to pH 7.0. Pepsin activity was estimated by measuring
      enzymatic activity. Saline, pentagastrin and histamine were infused
      intravenously. PHA or bovine serum albumin (BSA) were dissolved in saline and
      given intragastrically through the gastric cannula. PHA significantly inhibited
      basal acid secretion. Inhibition of acid output reached 72% during the first
      collection period following PHA administration when compared, then gradually
      disappeared. Pentagastrin-stimulated acid secretion was repressed dose
      dependently by PHA as well. Maximal inhibition was observed during the first 30
      min following application of PHA. Histamine-stimulated acid secretion was
      inhibited by PHA in a similar manner. Pepsin secretion was not affected by PHA
      under either basal or stimulated conditions. These results provide evidence that
      PHA is a potent inhibitor of gastric acid secretion in conscious rats, but it
      does not affect pepsin output from the stomach.

PMID- 11595456
TI  - Portal hypertension and liver lesions in chronically alcohol drinking rats
      prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD
      116), and propranolol, but not ranitidine.
AB  - Liver lesions and portal hypertension in rats, following chronic alcohol
      administration, are a particular target for therapy. Portal hypertension (mm Hg)
      assessed directly into the portal vein, and liver lesions induced by 7.28 g/kg
      b.w. of alcohol given in drinking water for 3 months, were counteracted by a
      stable gastric pentadecapeptide BPC 157, GEPPPGKPADDAGLV, M.W. 1419, known to
      have a beneficial effect in a variety of models of gastrointestinal or liver
      lesions (10 microg or 10 ng/kg b.w. i.p. or i.g.) and propranolol (10 mg/kg b.w.
      i.g.), but not ranitidine (10 mg/kg b.w. i.g.) or saline (5 ml/kg b.w. i.p./i.g.;
      control). The medication (once daily) was throughout either the whole 3 months
      period (1) or the last month only (2) (last application 24 h before sacrifice).
      In the background of 7.28 g/kg/daily alcohol regimen similar lesions values were
      assessed in control rats following alcohol consumption, after 2 or 3 months of
      drinking. Both prophylactic and therapeutic effects were shown. After a period of
      2 or 3 months, in all control saline [intragastrically (i.g.) or
      intraperitoneally (i.p.)] treated rats, the applied alcohol regimen consistently
      induced a significant rise of portal blood pressure values over values noted in
      healthy rats. In rats that received gastric pentadecapeptide BPC 157 or
      propranolol the otherwise raised portal pressure was reduced to the values noted
      in healthy rats. Besides, a raised surface area (microm(2)) and increased
      circumference (microm) of hepatocyte or hepatocyte nucleus [HE staining, measured
      using PC-compatible program ISSA (VAMS, Zagreb, Croatia)] and an advanced
      steatosis [scored (0-4), Oil Red staining] (on 100 randomly assigned hepatocytes
      per each liver), an increased liver weight, all together parallel a raised portal
      pressure in controls. Some of them were completely eliminated (not different from
      healthy rats, i.e. portal pressure, the circumference and area of hepatocytes,
      liver weight), while others were markedly attenuated (values less than in
      drinking controls, still higher than in healthy rats, i.e. circumference and area
      of hepatocytes nucleus). On the other hand, ranitidine application attenuated
      only steatosis development. In summary, despite continuous chronic alcohol
      drinking, pentadecapeptide BPC 157, and propranolol may prevent portal
      hypertension as well as reverse already established portal hypertension along
      with related liver disturbances.

PMID- 11595457
TI  - Gene expression and gene therapy in experimental duodenal ulceration.
AB  - Gastroduodenal ulceration is still poorly understood and changes in gene
      expression may provide new mechanistic insights. Previously, we demonstrated that
      angiogenic growth factors are potent ulcer healing agents, and the synthesis of
      bFGF, PDGF and VEGF is enhanced early in duodenal ulcer healing. The initial
      molecular event in duodenal ulceration seems to be the organ-specific early
      release of ET-1 in the pre-ulcerogenic stages after the administration of
      duodenal ulcerogen cysteamine in rats. We also briefly review here data from
      literature indicating a central role of ET-1 in gastroduodenal ulceration. After
      studying the involvement of immediate early genes (e.g. egr-1, Sp1) in ulcer
      development, we now investigated expression of other genes in the duodenal mucosa
      in the early stages of chemically induced duodenal ulceration in rats. Following
      a brief review of principles of gene expression and gene therapy, we review our
      preliminary gene expression studies, involving monitoring about 1200 genes which
      revealed about 160 signals and prominent changes in about 30 genes in the early
      stages of experimental duodenal ulceration. Cysteamine enhanced ET-B receptor
      gene expression in 30 min, while transcription factors (MAX, STAT 3) showed
      increased expression in 12 h. We recently also initiated gene therapy studies to
      enhance the local synthesis of PDGF and VEGF to accelerate duodenal ulcer
      healing, using a single dose of naked DNA (ND) or adenoviral (AV) vectors of VEGF
      and PDGF in rats with cysteamine-induced duodenal ulcers. Gene therapy with ND or
      AV of VEGF or PDGF significantly accelerated chronic duodenal ulcer healing, and
      increased levels of VEGF and PDGF were detected by Western blotting and ELISA in
      duodenal mucosa after both VEGF and PDGF gene therapy. Thus, gene expression
      studies provide new insights into the molecular mechanisms of duodenal ulceration
      and VEGF or PDGF gene therapy seems to be a new option to achieve a rapid ulcer
      healing.

PMID- 11595458
TI  - Regeneration of gastric mucosa during ulcer healing is triggered by growth
      factors and signal transduction pathways.
AB  - An ulcer is a deep necrotic lesion penetrating through the entire thickness of
      the gastrointestinal mucosa and muscularis mucosae. Ulcer healing is a complex
      and tightly regulated process of filling the mucosal defect with proliferating
      and migrating epithelial and connective tissue cells. This process includes the
      re-establishment of the continuous surface epithelial layer, glandular epithelial
      structures, microvessels and connective tissue within the scar. Epithelial cells
      in the mucosa of the ulcer margin proliferate and migrate onto the granulation
      tissue to re-epithelialize the ulcer. Growth factors, such as epidermal growth
      factor (EGF), basic fibroblast growth factor (bFGF), trefoil peptides (TP),
      platelet derived growth factor (PDGF) and other cytokines produced locally by
      regenerating cells, control re-epithelialization and the reconstruction of
      glandular structures. These growth factors, most notably EGF, trigger epithelial
      cell proliferation via signal transduction pathways involving EGF-R- MAP
      (Erk1/Erk2) kinases. Granulation tissue, which develops at the ulcer base,
      consists of fibroblasts, macrophages and proliferating endothelial cells, which
      form microvessels under the control of angiogenic growth factors. These growth
      factors [bFGF, vascular endothelial growth factor (VEGF) and angiopoietins]
      promote angiogenesis--capillary vessel formation--thereby allowing for the
      reconstruction of microvasculature in the mucosal scar, which is essential for
      delivery of oxygen and nutrients to the healing site. The primary trigger to
      activate expression of angiogenic growth factors and their receptors appears to
      be hypoxia. During ulcer healing expression of growth factor genes is tightly
      regulated in a temporally and spatially ordered manner.

PMID- 11595459
TI  - Role of leptin in the stomach and the pancreas.
AB  - Leptin, a 16 kDa protein encoded by the ob gene, is known mainly for its role in
      the regulation of food intake, body composition and energy expenditure through a
      central feedback mechanism. Initially leptin was considered as an ob gene product
      of adipocytes but recently the presence of leptin and its receptors have been
      revealed in other organs including gastric mucosa and the pancreas and found to
      be released from these organs by cholecystokinin (CCK), gastrin and ordinary
      feeding. Furthermore, leptin was found to mimic the action of CCK on gastric and
      pancreatic integrity, while reducing the food intake and to affect gastric and
      pancreatic secretion. This report emphasizes the role of leptin originating from
      the gastrointestinal tract acting synergistically with CCK at the hypothalamus
      level on the mechanism of food intake and locally on the protection of gastric
      mucosa and the pancreas against noxious agents and to maintain tissue integrity.

PMID- 11595460
TI  - Effect of Helicobacter pylori infection and eradication on gastric epithelial
      cell proliferation and apoptosis.
AB  - OBJECTIVES: the effect of Helicobacter pylori infection on gastric epithelial
      cell proliferation and apoptosis is still controversial. Our aim was to evaluate
      the effect of H. pylori infection on cell kinetic parameters in normal gastric
      epithelium, gastritis with/without intestinal metaplasia and gastric cancer.
      PATIENTS AND METHODS: antral biopsies were taken from 121 patients (61 women, 60
      men, mean age 58.5+/-14.3 years of age) who underwent routine gastroscopy for
      upper gastrointestinal symptoms. Sections were scored for normal epithelia
      (n=15), gastritis without intestinal metaplasia (n=74), gastritis with intestinal
      metaplasia (n=24), and gastric adenocarcinoma (n=8). Fifty-two patients had H.
      pylori positive gastritis, and success of H. pylori eradication therapy was
      controlled in 12 cases, all with intestinal metaplasia. To characterize cell
      proliferation and assess apoptosis, immunohistochemistry [Proliferating Cell
      Nuclear Antigen (PCNA)], histochemistry [Argyrophil Nucleolar Organizer Regions
      (AgNOR)], and terminal deoxynucleotidyl transferase (TdT)-mediated
      deoxyuridinetriphosphate (dUTP) nick end-labeling (TUNEL) were used,
      respectively. RESULTS: both cell proliferation and apoptosis is was higher in
      chronic gastritis when compared with normal epithelia, but neither PCNA LI
      (54.79+/-19.1 vs. 53.20+/-20.7) nor AgNOR counts (291.43+/-44.3 vs. 277.8+/
      57.54) were different in H. pylori positive versus negative chronic gastritis. A
      significant positive correlation (P<0.05) was found in this group between PCNA
      and AgNOR techniques. Apoptosis was significantly higher (P<0.05) in H. pylori
      positive cases only when intestinal metaplasia was not present. Cell
      proliferation in intestinal metaplasia decreased to the activity of normal
      epithelium after successful eradication of H. pylori but remained high if
      eradication therapy failed. CONCLUSIONS: epithelial cell proliferation does not
      depend on H. pylori status in chronic gastritis. H. pylori increases apoptosis
      only in the absence of intestinal metaplasia.

PMID- 11595461
TI  - Epidermal growth factor and prostaglandin E(2) accelerate mucosal recovery from
      stress-induced gastric lesions via inhibition of apoptosis.
AB  - The repair of damaged gastric mucosa is a complex process involving
      prostaglandins (PG) and mucosal growth factors such as epidermal growth factor
      (EGF). Recently, we postulated that the increased occurrence of apoptosis in the
      gastric epithelium might be of pathophysiological importance in the development
      of stress lesions. The aim of the present study was to assess the effect of the
      pretreatment of rats, exposed to 3.5 h of water immersion and restraint stress
      (WRS), with EGF and PG (16,16 dmPGE(2)) on the number of stress lesions, recovery
      of gastric mucosa from stress and the expression of apoptosis related genes such
      as caspase-3 and antiapoptotic bcl-2. Rats were divided in following groups: (1)
      vehicle; (2) EGF 100 microg/kg i.p.; (3) 16,16 dm-PGE(2) (5 microg/kg i.g.) and
      caspase-1 inhibitor (ICE-I; 100 microg/kg i.p.). One hour later, the rats were
      exposed to 3.5 h of WRS and then sacrificed immediately (0 h) or at 6, 12, or 24
      h after WRS. The number of acute gastric lesions was determined. Gastric
      epithelial apoptosis was assessed by TUNEL staining. In addition, mRNA expression
      of caspase-3, Bcl-2 and proinflammatory cytokines (IL-1 beta, TNFalpha) was
      assessed by RT-PCR. PGE(2) generation in gastric mucosa and luminal EGF were
      determined by RIA. Exposure to WRS resulted in the development of multiple acute
      stress erosions ( approximately 18) which almost completely healed during 24 h.
      The gastric blood flow was significantly reduced (approximately 70% of intact
      mucosa) immediately after WRS. The expression of mRNA for IL-1 beta and TNF alpha
      reached their peak at 12 h after stress exposure. The apoptosis rate was highest
      at 6 h after WRS and was accompanied by the highest caspase-3 expression. In rats
      pretreated with EGF or 16,16 dm-PGE(2), a significant decrease in caspase-3 mRNA
      and upregulation of bcl-2 mRNA as observed as compared to vehicle controls.
      Caspase-1 inhibitor significantly reduced the number of stress lesions. We
      conclude that EGF and PGE(2) accelerate healing of stress-induced lesions due to
      the attenuation of apoptosis via upregulation of bcl-2 in gastric mucosa.
      Inhibitors of apoptosis accelerate healing of stress lesions and may be
      potentially effective agents in the healing of damaged gastric mucosa.

PMID- 11595462
TI  - Determination of Helicobacter pylori cagA, vacA genotypes with real-time PCR
      melting curve analysis.
AB  - OBJECTIVES: genotypes of Helicobacter pylori are the focus of interest because
      they play a prominent role in mucosal injury. The purpose of this study was to
      determine cagA and vacA genotypes of H. pylori using real-time polymerase chain
      reaction (PCR) method with a double strain DNA binding SYBR Green I.dye, and to
      compare this with those of two immunohistochemical methods. METHODS: forty-three
      paraffin-embedded biopsy tissue samples were examined by histology, epidermal
      growth factor receptor (EGFR), proliferating cell nuclear antigen (PCNA)
      immunohistochemistry and melting curve analysis of real-time PCR. RESULTS: the
      presence of cagA gene was associated with a significantly higher frequency of
      gastritis (P=0.003) than that of vacA gene with intestinal metaplasia (P=0.045).
      Significant difference was found between the presence of cagA gene and EGFR
      expression in intestinal metaplasia cases in comparison with cagA negative
      samples (P=0.0418). Statistically significant difference was detected between
      increased cell proliferation and the presence of gastritis. CONCLUSIONS: this
      method seems to be suitable for H. pylori genotype determination. Sensitivity,
      speed and simplicity are key areas in the development of PCR assays for H.
      pylori. Results supported the notion that infection with cagA positive H. pylori
      strain causes more augmentated cell proliferation in the stomach mucosa.

PMID- 11595463
TI  - NSAIDs inhibit the activation of egr-1 gene in microvascular endothelial cells. A
      key to inhibition of angiogenesis?
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, indomethacin
      (IND), ibuprofen and newer cyclooxygenase-2 selective NSAIDs (e.g. celecoxib)
      delay gastric ulcer healing partly through the inhibition of angiogenesis, but
      the molecular mechanisms involved are not fully elucidated. Effective
      angiogenesis is required for ulcer healing to supply oxygen and nutrients to the
      healing site. The early growth response factor (Egr-1) is a transcription factor,
      which is rapidly activated by a variety of extracellular signals or tissue injury
      and is important for angiogenesis to occur. This study aimed to determine whether
      indomethacin (IND) and/or the selective COX-2 inhibitor, NS-398, interfere with
      egr-1 gene expression in human microvascular endothelial cells (HMVEC) in
      response to vascular endothelial growth factor (VEGF) stimulation. HMVEC were
      treated with 0.5 mM IND or 100 microM NS-398 for 16 h, and then VEGF (10 ng/ml)
      or vehicle was added. Egr-1 mRNA and protein expression levels were determined by
      RT-PCR and Western-blotting, respectively. VEGF treatment caused a significant
      elevation of Egr-1 mRNA (261+/-21%, P<0.001) and protein expression (174+/-15%,
      P<0.01) vs. vehicle. IND pre-treatment significantly inhibited VEGF-induced Egr-1
      mRNA expression by 29+/-4% (P<0.01) and protein expression by 41+/-8% (P<0.05).
      NS-398 inhibited VEGF-induced Egr-1 mRNA and protein expression by 23+/-3% and
      35+/-4%, respectively (both P<0.01). Since transcriptional activation of egr-1 is
      responsible for expression of proteins involved in proliferation of endothelial
      cells essential for angiogenesis, these results provide a new mechanism for
      NSAIDs' interference with angiogenesis.

PMID- 11595464
TI  - Effects of putative galanin antagonists M35 and C7 on rat exocrine pancreas.
AB  - Galanin is a neuropeptide having a wide range of biological actions. Recently
      selective galanin receptor antagonists such as M35 [galanin(1-12)-Pro
      bradykinin(2-9)-amide] and C7 [galanin(1-12)-Pro-spantide-amide] have been
      described. These antagonists have blocked the actions of galanin on flexor
      reflex, glucose-induced insulin secretion, and acetyicholine release from
      hippocampus. Our present aim was to investigate whether M35 and C7 can affect
      galanin-induced inhibition of pancreatic enzyme secretion in rats. Pancreatic
      enzyme secretion was studied in urethane-anesthetized rats supplied with jugular
      vein catheter and pancreatic cannula. Amylase secretion evoked by submaximal CCK
      8 stimulation was inhibited dose-dependently by galanin in anesthetized rats.
      Surprisingly, neither M35 nor C7 was able to inhibit the responses of the
      exocrine pancreas to galanin. However, both putative galanin receptor antagonists
      behaved as agonists in our experimental models. Our data suggest that the effects
      of galanin on pancreatic enzyme secretion are not mediated by M35- or C7
      sensitive galanin receptors. Therefore, these galanin receptors are different
      from those described in the central nervous system.

PMID- 11595465
TI  - Different affinity states of CCK(1) receptors on pancreatic acini and gastric
      smooth muscle in the rat.
AB  - It has recently been shown that--after chronic cholecystokinin (CCK) treatment-
      an adaptation of pancreatic secretory but not gastric motor function does occur.
      Recent studies indicate that the CCK(1)-receptor exists in two (i.e. high and
      low) affinity states, which could be distinguished by the CCK-analogue JMV-180.
      CCK occupancy of high and low affinity sites is thought to be related to the
      initiation of different intracellular events and consequent biological responses.
      Affinity states of CCK(1)-receptors on pancreas and gastrointestinal (GI) smooth
      muscle could be different and this can offer an explanation for the different
      effects of CCK on pancreatic and gastric growth. We therefore studied the
      affinity states of CCK(1)-receptors on isolated rat pancreatic acini and gastric
      smooth muscle preparations. When acini were incubated with increasing
      concentrations of CCK-8, a biphasic (i.e. stimulation followed by inhibition)
      effect on amylase release was observed. JMV-180 caused only stimulation of enzyme
      release and combined JMV-180 and CCK stimulation (at submaximal doses) resulted
      in an additive secretory response. CCK-8 induced contractions of pyloric, antral
      and fundic muscle in a concentration-dependent manner. The response was
      monophasic, reaching a plateau. JMV-180 had only a very weak effect on these
      preparations. On the contrary, it inhibited CCK-induced contractions in a
      competitive manner, the concentration-response curve to CCK being shifted to the
      right by the CCK analogue. Our data suggest that the affinity states of CCK(1)
      receptors on rat pancreatic and gastric tissue are different. On pancreatic acini
      CCK(1)-receptors exist in both high- and low-affinity states whose occupation is
      followed by the sequence of intracellular events leading to growth. In contrast,
      occupation of low affinity receptors (the only ones present in the GI smooth
      muscle) does not lead to cell proliferation. This difference therefore explains
      the different adaptive response of the pancreas and the stomach to chronic CCK
      administration. Furthermore, different affinity states of CCK(1)-receptors may
      mediate different functions of the digestive tract.

PMID- 11595466
TI  - Therapy for chronic hepatitis C.
AB  - BACKGROUND/AIMS: in Hungary, over the past 5 years more than 900 patients with
      chronic hepatitis C have been examined for treatment with interferon at 16 major
      hepatology centres, using unified diagnostic and therapeutical criteria. Authors
      give an account of their experiences on the clinical features of patients with
      chronic hepatitis C and report the results of the interferon therapy. METHODS: a
      total of 993 patients--virtually the entire Hungarian hepatitis C patient
      population who had been referred for interferon treatment--were included in the
      program. Actually, the sustained efficacy of the therapy was evaluated in 724
      cases. Treatment protocols (dose of interferon and duration of therapy) have
      changed with time from a weekly dose of 3x3 MU IFN for 6 months in the first
      period, to 3x3-5 MU for 12 months in the second period, and finally in the third
      period a combination therapy with ribavirin has also been introduced. RESULTS: in
      the first period, the end-of-treatment response (ETR) was 35%, sustained response
      (SR) 13%, the second phase schedule resulted in 42% ETR and 22% SR, while in the
      third period, ETR was 49% and SR 36%, respectively. Fibrosis in histology and
      baseline pretreatment HCV-RNA level appeared as predictors of response. The
      duration of treatment and the total dose of interferon exerted a moderate effect
      on therapeutic efficacy. Neither age nor gender influenced the outcome.
      CONCLUSIONS: our results-obtained in a Central East European country-are in
      accordance with findings of suboptimal efficacy of traditional interferon
      monotherapy for chronic hepatitis C reported in the West, and suggest the benefit
      of the combination treatment of interferon with ribavirin.

PMID- 11595467
TI  - Treatment of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a presumed autoimmune disease of the liver,
      which predominantly affects middle age women. Most patients are diagnosed when
      asymptomatic. The disease is characterised by chronic, granulomatous inflammation
      of the small bile ducts, which leads to progressive ductopenia, cholestasis,
      fibrosis, cirrhosis and eventual liver failure. All PBC patients with abnormal
      liver biochemistry should be considered for therapy. Ursodeoxycholic acid (URSO)
      treatment reduces intracellular hydrophobic bile acid levels and thereby may have
      a cytoprotective effect on cell membranes. URSO may also act as an
      immunomodulating agent. Multicenter randomised controlled trials proved that the
      treatment is associated with a marked improvement in serum biochemical markers of
      cholestasis, i.e. bilirubin, ALP, GGT, including fall in serum cholesterol
      levels. Treatment does not seem to benefit the symptoms of fatigue, pruritus, and
      osteoporosis. UDCA has been shown when given in a dose of 15 mg/kg daily for up
      to 4 years to prolong the time to liver transplantation or death.
      Immunosuppressive therapy: based on the immunological abnormalities, several
      immunosuppressive drugs have been tested. Neither azathioprine nor cyclosporine
      was found in large enough trials to show beneficial effect on survival. D
      penicillamine, cholchicin, methotrexat, prednisolone were found without
      significant long-term benefit. Combination therapy with URSO and budenoside
      appears to add some benefit to URSO monotherapy, but further studies are needed.
      Liver transplantation. The most crucial question is the timing. Serum bilirubin,
      Mayo risk score and some other factors such as uncontrollable pruritus and severe
      osteoporosis influence the decision. Recurrence of PBC in allograft is rare, the
      progress is slow, and is no reason for not recommending transplantation.
      Symptomatic treatment of pruritus, sicca syndrome and preventive treatment of
      osteoporosis, neuropathy and fat soluble vitamin deficiency is also important.

PMID- 11595468
TI  - Multimodality treatment resulting in long-term survival in hepatocellular
      carcinoma.
AB  - The early detection and complex therapy of the hepatocellular carcinoma (HCC) is
      one of the most seasonable questions of the gastroenterology-oncology, because of
      the increasing prevalence of the primary liver cancer. The course of the
      hepatocellular carcinoma is rapid, untreated patients rarely live over 5-6
      months. Combination of different treatment modalities in HCC can offer the best
      chances for survival. If possible, a surgical resection should be the primary
      procedure, followed by adjuvant cytostatic treatment and chemoembolisation. The
      authors report three cases with HCC with extremely long survival. The long-term
      survival achieved by multimodality therapy, as presented in these cases, seems to
      justify aggressive therapeutical approaches in HCC. It has been concluded, that
      early detection and complex, aggressive multimodality treatment--even repeated
      liver resections and surgical elimination of duplex distant metastases--can
      result in long-term survival with a good quality of life.

PMID- 11595469
TI  - Hepatitis viruses and hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is among the most frequent malignancies worldwide.
      Hepatitis viruses, such as the hepatitis B virus (HBV) and hepatitis C virus
      (HCV) are undoubtedly listed in the etiology of HCC. Studies show that, in the
      near future, viral hepatitis will carry increasing weight in the etiology of HCC.
      This review briefly discusses the known carcinogenic effects of HBV and HCV in
      the light of experimental and human studies. The data show that viral proteins
      may directly interfere with gene products responsible for cell proliferation and
      cell growth. Many other signal transduction cascades may be affected as well.
      Direct integration of HBV viral sequences into the host genome increases the
      genomic instability. The genomic imbalance allows the development and survival of
      malignant clones bearing defected genomic information. HBV and HCV infection
      induces indirect and direct mechanisms through cellular damage, increased
      regeneration and cell proliferation, therefore enhancing the development of HCC.

PMID- 11595470
TI  - Acid, helicobacter and immunity: a new paradigm for oesophagogastric cancer.
AB  - Epidemiological evidence has clearly shown a highly significant relationship
      between Helicobacter pylori infection and the development of duodenal ulcer and
      distal gastric adenocarcinoma. Despite H. pylori being a common aetiological
      factor for both disorders, the two disease phenotypes are virtually mutually
      exclusive. This indicates that the host response to infection has a pivotal role
      in determining outcome; these disease phenotypes relate to the effect of
      infection on gastric acid secretion, duodenal ulcer being closely related to
      sustained acid secretion whereas gastric cancer follows gastric atrophy and
      impaired gastric acid secretion. Cancer at the oesophageal junction and that
      associated with Barrett's oesophagus is now the most rapidly increasing tumour in
      the gastrointestinal tract. The challenge for the next millennium, therefore, is
      to try and develop methods for identifying patients at risk of developing
      oesophagogastric cancer. A common feature in the pathogenesis of both gastric and
      oesophageal adenocarcinoma is inflammation presenting clinically as gastritis and
      oesophagitis. The pathway from gastritis to gastric atrophy, dysplasia and
      carcinoma is thought to be a multi-step process, probably triggered by free
      radicals within the gastric epithelium and increased exposure to luminal
      carcinogens. However, it has been unclear as to which aspect of the host response
      determines whether an individual will move along the neoplasia pathway. Recent
      work has shown that qualitative aspects of the immune environment in the stomach
      may account for a substantial part of the phenotypic divergence following H.
      pylori infection. Interleukin-1 beta polymorphisms relate closely to the
      propensity for an individual to develop distal gastric cancer and maybe useful
      for predicting risk in family members. In Barrett's oesophagus, we have recently
      shown that the immune environment may also be important in determining whether an
      individual will develop cancer. Although we did not find that Barrett's
      oesophagus was a profoundly inflammatory condition (unlike esophagitis in the
      squamous epithelium), where there was evidence of inflammation it was
      qualitatively different from that of oesophagitis in that a Th-2 response with
      increased expression of IL-4 predominated in Barrett's, whereas a Th-1
      proinflammatory response characterised oesophagitis in squamous epithelium. It
      seems likely that the specific immune environment within Barrett's metaplasia may
      be an important driver towards dysplasia and carcinoma. Thus, the immune
      environment in the stomach and esophagus may be critical in determining whether
      an individual is at risk of developing neoplastic complications of H. pylori
      infection and gastroesophageal reflux. Identification of the genetic factors
      which underpin these responses may ultimately result in development of methods to
      identify individuals at high risk.

PMID- 11595471
TI  - Gastric mucosal changes induced by long term infection with Helicobacter pylori
      in Mongolian gerbils: effects of bacteria eradication.
AB  - Helicobacter pylori infection has been reported to induce various mucosal
      changes, including gastric adenocarcinoma, in Mongolian gerbils 62 weeks after
      inoculation. Using Mongolian gerbils, this study examined whether or not
      eradication of the bacteria with drugs at specified times after infection
      prevents the development of mucosal changes. After orally inoculating with H.
      pylori (TN2GF4, vacA- and cagA-positive), the animals were killed 18 months
      later. Four or 8 months after H. pylori inoculation, eradication was performed by
      concurrent treatment with omeprazole+clarithromycin. Immediately after treatment
      ended, in both the 5 and 9 month groups, it was verified that H. pylori was
      completely eradicated. Autopsy performed 18 months after H. pylori inoculation
      revealed gastric hyperplastic polyps with erosive lesions and ulcers that were
      grossly visible in the non-treated control group. In addition, atrophic
      gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were
      histologically observed in the animals. In animals eradicated after 4 months and
      autopsied after 18 months, however, such mucosal changes were not observed. In
      contrast, intestinal metaplasia and mucosal atrophy was observed in animals
      eradicated after 8 months and autopsied after 18 months. It was concluded that
      early eradication of H. pylori infection with drug therapy can prevent severe
      gastric mucosal changes, to include adenocarcinomas, in Mongolian gerbils.

PMID- 11595472
TI  - Six regimens for the eradication of Helicobacter pylori (Hp) in duodenal ulcer
      patients: three consecutive trials (1995-1999).
AB  - AIM: to present our experience in eradicating Hp in three consecutive trials
      performed between 1995 and 1999. METHODS: 320 duodenal ulcer outpatients have
      been enrolled in three open, prospective controlled trials. Hp infection was
      confirmed by Giemsa stain and Rut. In Trial I, 52 cases received 20 mg omeprazole
      + 2 x 250 mg clarithromycin + 2 x 500 mg tinidazole (OCT), 48 patients were given
      20 mg omeprazole, 2 x 1000 mg amoxicillin + 2 x 500 mg metronidazole (OAM) for 7
      days; in Trial II, 48 cases received 40 mg pantoprazole + 2 x 1000 mg amoxicillin
      + 2 x 500 mg clarithromycin (PAC) for 7 days and 5l cases 2 x 400 mg ranitidin
      bismuth citrate + 2 x 500 mg clarithromycin for 14 days (RBC-C); in Trial III, 60
      cases were treated with 2 x 30 mg lansoprazole + 2 x 250 mg clarithromycin + 2 x
      500 mg metronidazole and 6l patients received 2 x 400 mg ranitidin bismuth
      citrate+2 x 250 mg clarithromycin + 2 x 500 mg metronidazole (RBC-CM). The
      patients were controlled within 4-6 weeks by endoscopy in trials I-II and 13C
      urea breath test in trial III. RESULTS: Eradication rates on ITT/PP basis were:
      OCT: 72.3/80.2% vs OAM 51.2/63.5% (P = 0.02/P = 0.03); PAC: 80.8/88.3% vs RBC-C
      80.3/85.4% (P = 0.65/0.67) and LCM 78.3/92.1% vs RBC-CM 78.7/90.5% (P = 0.86/P =
      0.93). Side effects occurred in 5.2, 8.6, 9.5, 14.5, 13.5 and 18.3% of the cases.
      CONCLUSION: Regimens using 2 x l PPI or RBC + 2 antibiotics for l week proved to
      be the most effective for Hp eradication in duodenal ulcer patients.

PMID- 11595473
TI  - Effects of dexamethasone and FK506 on Helicobacter pylori-induced gastritis and
      bacterial viability in Mongolian gerbils.
AB  - FK506 and dexamethasone were used to investigate whether or not immunosuppression
      affects H. pylori colonization and gastric mucosal damage induced by Helicobacter
      pylori in Mongolian gerbils. Two weeks after H. pylori infection, FK506 and
      dexamethasone or vehicle alone were subcutaneously administered once daily for
      the following 2 weeks. FK506 or vehicle alone was administered subcutaneously
      once daily for 5 weeks (1 week before and 4 weeks after infection). In H. pylori
      infected animals for 4 weeks, hemorrhagic erosions and inflammatory responses
      (neutrophil infiltration and lymphoid follicle formation) were induced in gastric
      mucosa at an incidence of 100%. Both FK506 and dexamethasone administered for 2
      weeks markedly reduced such mucosal changes. In these animals, H. pylori
      viability in the stomach was significantly elevated. FK506 administered for 5
      weeks also significantly inhibited the hemorrhagic erosions, edema and neutrophil
      infiltration in the stomach. H. pylori viability was slightly elevated as
      compared with the control. It was concluded that the host immune responses might
      play dual roles both by deteriorating gastritis induced by H. pylori and by
      protecting against H. pylori infection in its early stage.

PMID- 11595474
TI  - Attenuation of Helicobacter pylori endotoxin-provoked rat intestinal inflammation
      by selective inhibition of the inducible nitric oxide synthase.
AB  - We studied the actions of purified Helicobacter pylori endotoxin (3 mg kg(-1),
      i.v.) on rat intestinal vascular permeability (assessed by the radiolabelled
      human serum albumin leakage technique) and on nitric oxide synthase induction
      (assessed by the citrulline assay) 4 h later. We found increased albumin leakage
      and expression of the inducible nitric oxide synthase in jejunum and colon,
      effects reversed by a selective inducible nitric oxide synthase inhibitor N-(8
      (aminomethyl)benzyl)-acetamidine (1400W; 0.2-1 mg kg(-1), s.c., concurrently with
      endotoxin). Thus, H. pylori endotoxin seems to be capable of provoking an
      inflammatory response in the rat intestinal tissue. Systemic liberation of H.
      pylori endotoxin might possibly attenuate jejunal and colonic mucosal barrier
      function, a process mediated by the expression of the inducible nitric oxide
      synthase.

PMID- 11595475
TI  - One year follow-up of patients after successful helicobacter pylori eradication
      therapy.
AB  - The aim of this study was to investigate the Helicobacter pylori (Hp) status of
      patients who underwent successful eradication therapy 1 year prior to the study
      and to evaluate their current symptoms. METHODS: all of the patients were
      initially evaluated by oesophago-gastro-bulboscopy and the Hp status was
      determined by at least two different methods [rapid urease test, histology or
      urea breath test (UBT)]. The Hp infection was treated with a 1-week triple
      therapy protocol, and the UBT was repeated 4-6 weeks later. We invited back 110
      patients who had negative post-eradication UBT results 12+/-3 months prior to the
      study period. UBT was repeated and a questionnaire was completed about the
      previous and present complaints and medication. RESULTS: 80 of the 110 patients
      (73%) came back for the follow-up. Twenty five patients had peptic ulcer disease,
      36 patients had gastritis or duodenitis without erosive lesions, and 19 patients
      had erosive form of gastritis or duodenitis initially. All of the patients except
      one in the erosive gastritis group had negative control UBT 1 year after the
      eradication, which means 1.25% recurrence rate within 1 year. The eradication
      therapy completely revealed the symptoms of 16 patients in the ulcer group (64%),
      13 patients in the gastroduodenitis group (36%, P=0.03 vs. ulcer patients), 10
      patients with erosive gastroduodenitis (52%), but this was only temporary. One
      year after the eradication therapy seven of the ulcer patients (28%), 11 patients
      with gastroduodenitis (31%) and seven patients with erosive gastroduodenitis
      (37%) were symptom-free. Most of the patients had epigastric pain (44%),
      heartburn (43%) and/or abdominal distension (33%). Nine ulcer patients (36%), 10
      patients with gastroduodenitis (28%) and five patients with erosive
      gastroduodenitis (26%) were taking H(2)-blockers regularly. CONCLUSION: the 1
      month post-eradication UBT was probable true negative in all of the evaluated
      cases, since 79 patients (98.75%) were also negative after 1 year. The Hp
      recurrence rate is very low (1.25%) in a 1-year period. The symptoms were
      relieved shortly after eradication therapy in the majority of patients with ulcer
      disease or erosive lesions. However, significantly smaller portion of the
      patients with gastroduodenitis became symptom-free. Only about one third of the
      treated patients remained symptom-free 1 year after the eradication.

PMID- 11595476
TI  - mRNA expression of cytokines and chemokines in the normal gastric surface mucous
      epithelial cell line GSM06 during bacterial infection with Helicobacter felis.
AB  - BACKGROUND AND AIM: A group of the proinflammatory and chemotactic cytokines
      (chemokines) has been considered as an important factor in the pathomechanism of
      different bacterial diseases, among them the common Helicobacter pylori
      infection. Experimental results obtained with gastric biopsy samples of H. pylori
      positive patients, and with H. pylori infected tumor originated gastric cell
      lines indicated that these cytokines have essential roles in the development and
      maintenance of the immune response and inflammation of the gastric mucosa during
      H. pylori infection. Although the mRNA expression was shown in these biopsy
      samples and cell lines, it is not yet proved that the normal gastric mucosal
      epithelial cells themselves express these cytokines. The establishment of a
      gastric surface mucous cell line with non-tumor origin (GSM06), and the usage of
      Helicobacter felis as a model of the classic H. pylori infection gave us the
      possibility to check this question. MATERIALS AND METHODS: in this study GSM06
      cells were infected with different numbers (10(5), 10(6), 10(7), 10(8), 10(9)
      bacterium/ml medium) of H. felis for two different time periods (2, 4 h). Cells
      treated with medium only were used as control. Then the mRNA expression of the
      following cytokines was measured by RT-PCR method in the GSM06 cells:
      proinflammatory cytokine IL1-beta, and chemokine RANTES, eotaxin, MCP-1, MIP1
      alpha and MIP1-beta. RESULTS: we found that neither mRNA of the investigated
      cytokines was expressed constitutively, however the GSM06 cells expressed the
      mRNA of each cytokine during H. felis infection. CONCLUSION: our results prove
      that normal gastric surface mucous epithelial cells express immunologically
      active peptides during H. felis infection. We may suppose that the epithelial
      cells of the gastric mucosa contribute to the immune response and inflammation by
      expressing proinflammatory (IL1-beta) and chemotactic (RANTES, eotaxin, MCP-1,
      MIP1-alpha and beta) cytokines during H. pylori infection in human.

PMID- 11595477
TI  - Eradication of Helicobacter pylori has no effect on gastric acidity in duodenal
      ulcer patients--evaluation of 24-h pH monitoring.
AB  - It is accepted that eradication of Helicobacter pylori leads to healing of
      chronic active gastritis facilitates ulcer healing and prevents ulcer recurrence
      in duodenal ulcer (DU) patients. However, it is not entirely known whether the
      eradication of the bacteria normalizes gastric acid secretion and abolishes
      dyspeptic symptoms after ulcer healing. This study was aimed to evaluate the
      intragastric acidity and dyspeptic complaints before, and 3 months after,
      eradication in 18 endoscopically proven H. pylori positive DU patients. Gastric
      pH was measured by 24-h continuous intraluminal recording, serum gastrin
      measurements and Congo-red tests were also performed. Dyspeptic complaints and
      antacid consumptions were recorded in diary cards, antisecretory therapy was not
      allowed after the cessation of eradication therapy. Endoscopy, H. pylori status
      and Congo-red tests were controlled at the 6th and 12th week, while pH
      measurements and serum gastrin tests were performed at inclusion and 3 months
      later. Three patients dropped out and in 14 out of the remaining subjects healing
      of DUs and successful eradication was achieved by the 6th and 12th week controls.
      The 24-h median pH and the percentage of 24-h pH readings under pH 3 were not
      changing significantly by the 3-month controls (from 1.9+/-0.5 to 1.8+/-0.4 and
      from 52.6+/-5.5% to 58.6+/-5%, respectively). Similarly, no significant changes
      were observed in serum gastrin levels and dyspeptic symptom scores (from 72+/-7
      pg/ml to 56.7+/-8 pg/ml and from 2.69+/-0.4 to 1.26+/-0.3, respectively). The
      antacid consumption was almost stable when compared with the pre- and post
      eradication periods. It was concluded that despite successful H. pylori
      eradication and healing of DU, intragastric acidity does not change significantly
      at least 3 months after the therapy. The persisting dyspeptic symptoms and the
      need for antacid consumption suggest that some healed ulcer patients require
      antisecretory therapy in the post-eradication period.

PMID- 11595478
TI  - Genetic factors in the development of gastric precancerous lesions--a role of
      Helicobacter pylori ?
AB  - Helicobacter pylori is believed to predispose to gastric cancer by inducing
      gastric precancerous alterations. There is a well known predisposition to gastric
      cancer and the risk of developing it is greater in relatives of patients with
      familial cases of this malignancy. The aim of this study was to determine the
      prevalence of gastric precancerous lesions (atrophy and intestinal metaplasia)
      and their association with Hp infection in first-degree relatives in patients
      with noncardia gastric cancer. METHODS: Hp status and gastric histology assessed
      by upper gastrointestinal endoscopy, biopsies from the antral and body region,
      the rapid urease test and staining for Hp, inflammation, activity, atrophy and
      intestinal metaplasia (prevalence and grading) were studied in 108 first-degree
      relatives of patients with noncardia gastric cancer and compared with 73 controls
      with mild non-ulcer dyspepsia who had no cancer relatives and were examined in
      the same way. RESULTS: subjects with and without cancer relatives had a similar
      prevalence of Hp infection (49 vs. 47%). Endoscopy revealed a few asymptomatic
      duodenal ulcers and small hiatus hernias in Hp positive subjects of both groups.
      Hp positive relatives of gastric cancer had a markedly higher prevalence of
      atrophy than those with Hp negativity without cancer relatives (29 vs. 9%) and
      those with Hp negativity and cancer relatives (29 vs. 3%. Prevalence of
      intestinal metaplasia was also higher in those with Hp positivity and cancer
      relatives than in those without cancer relatives (15 vs. 5% and was not present
      in Hp negative subjects with cancer relatives. Inflammation and activity showed
      similar scores in subjects with and without cancer relatives with higher scores
      in both Hp positive groups. The prevalence of precancerous lesions in the
      relatives of gastric cancer was nearly always confined to those with Hp
      positivity. One year after eradication the prevalence of atrophy in cancer
      relatives decreased from 29 to 14%; prevalence of intestinal metaplasia remained
      without substantial changes. Scores for inflammation and activity were also lower
      after eradication. CONCLUSIONS: First-degree relatives of patients with gastric
      cancer have an increased prevalence of gastric precancerous abnormalities which
      are strongly confined to those with Hp infection. Eradication of Hp in these
      subjects with cancer relatives reduces the prevalence of precancerous lesions
      (atrophy) and grades of inflammation and activity. In view of these results,
      eradication of Hp should be offered to such subjects.

PMID- 11595479
TI  - Prevalence of the factor V Leiden mutation in human inflammatory bowel disease
      with different activity.
AB  - BACKGROUND: the developmental mechanism of inflammatory bowel disease (IBD) in
      patients is unknown, but it may be influenced by different environmental and
      genetical factors. AIMS of this study were: (1) to classify the IBD patients
      according the disease activity; and (2) to determine the presence of factor V
      Leiden mutation in IBD patients. PATIENTS AND METHODS: the observation was
      carried out in 49 patients with Crohn's disease (CD) and 29 patients with
      ulcerative colitis (UC). None of them had a history of thrombotic episodes. IBD
      was diagnosed by conventional clinical, endoscopic, radiological and histological
      criteria. The factor V Leiden mutation was detected by the polymerase chain
      reaction (PCR) method. Crohn's disease activity index (CDAI) was evaluated using
      the method of the National Cooperative Crohn's Disease Study. We determined the
      UC disease activity according to Truelove-Witts classification. RESULTS: The
      prevalence of factor V Leiden mutation was increased in both populations of the
      patients to compare it with healthy persons (14.28 and 27.58% vs. 5.26%, n=7/49
      and 8/29 vs. 3/57). The statistical analysis did not show a significant
      relationship between the CDAI or the Truelove-Witts grade in UC and the presence
      of Leiden mutation. CONCLUSION: the presence of factor V Leiden mutation probably
      has a role in the development of IBD. Our results suggest a higher prevalence of
      this mutation in Central European patients than in Southern, Northern Europe or
      America, may be due to the genetical differences of these populations.

PMID- 11595480
TI  - Leiden mutation (as genetic) and environmental (retinoids) sequences in the acute
      and chronic inflammatory and premalignant colon disease in human gastrointestinal
      tract.
AB  - BACKGROUND: Tumor, calor, dolor, pallor and functio laesa are together involved
      in the different acute and chronic inflammatory processes. The processes involved
      in the inflammation are determined by differently acquired and hereditary
      factors. Recently the presence of a new genetic marker (Leiden point mutation)
      was found in Crohn's disease and ulcerative colitis. On the other hand, the GI
      mucosal integrity was proven on gastrointestinal mucosal damage to be produced by
      different chemicals, xenobiotics, drugs. In human observations, the serum level
      of retinoids (vitamin A, lutein, zeaxanthin, alpha-, beta-carotene) was proven in
      patients with chronic gastrointestinal inflammatory bowel disease. The aims of
      this study were (1) to measure the prevalence of Leiden mutation; (2) to identify
      the changes in the serum retinoid level in patients with Helicobacter pylori
      infection of the stomach (n=24), hepatitis C infection (n=75), ileitis terminalis
      (Crohn's disease; n=49), ulcerative colitis (n=35), colon polyposis (n=59) and
      adenocarcinoma in colon polyps (n=9), and 57 healthy persons were used in the
      control group; (3) to compare the directions of the changes in the measured
      parameters in the acute (H. pylori and hepatitis C infections), chronic (ileitis
      terminalis, ulcerative colitis) GI inflammatory diseases and in colon polyposis
      without and with malignisation. METHODS: The Leiden mutation was measured by the
      method of polymerase chain reaction, the retinoid level in the patient's serum
      was measured by high liquid cromathografic method (HPCL). RESULTS: (1) It has
      been found that the prevalence of Leiden mutation increased significantly in
      patients with ileitis terminalis (P<0.001), ulcerative colitis (P<0.001), colon
      polyposis (P<0.001) and with colon polyps with malignisation (P<0.01). (2) Serum
      level of vitamin A and zeaxantin were decreased significantly in all group of
      patients except for the group with H. pylori infections. (3) alpha- and beta
      carotenes were found to be practically at the same level as those in the control
      groups, except in patients of colon polyps with malignisation. (4) The vitamin A,
      lutein, zeaxantin, alpha- and beta-carotenes were decreased in patients with
      ileitis terminalis. CONCLUSIONS: (1) The essential role of retinoids
      (carotenoids) as environmental factors are suggested for keeping GI mucosal
      integrity in human healthy subjects and patients. (2) Leiden mutation, as a
      genetic marker, can be used in the screening of patients with ileitis terminalis,
      ulcerative colitis and colon polyposis (without and with malignisation). (3) An
      opposite direction can be found between the increased prevalence of Leiden
      mutation and decrease of serum levels of retinoids in group of patients with
      ileitis terminalis, ulcerative colitis and colon polyposis (without and with
      malignisation).

PMID- 11595485
TI  - Principles of glutamatergic synapse formation: seeing the forest for the trees.
AB  - General principles regarding glutamatergic synapse formation in the central
      nervous system are beginning to emerge. These principles concern the specific
      roles that dendrites and axons play in the induction of synaptic differentiation,
      the modes of presynaptic and postsynaptic assembly, the time course of synapse
      formation and maturation, and the roles of synaptic activity in these processes.

PMID- 11595486
TI  - Presynaptic imaging techniques.
AB  - Understanding the detailed molecular events that support chemical synaptic
      transmission requires high-resolution methods that provide quantitative
      information combined with molecular specificity. In recent years, many new
      technological approaches, including genetically encoded fluorescent indicators,
      ultra-thin sectioning, and live-cell imaging have been brought to bear on
      understanding the cell biology and physiology of presynaptic terminals.

PMID- 11595487
TI  - Linkers, packages and pathways: new concepts in axonal transport.
AB  - The molecular mechanisms that generate efficient and directed transport of
      proteins and organelles in axons remain poorly understood. In the past year, many
      studies have identified specific transmembrane or scaffold proteins that might
      link motor proteins to their cargoes. These studies have also identified
      previously unsuspected pathways and raised the intriguing possibility that pre
      packaged groups of functionally related proteins are transported together in the
      axon. Evidence suggests that fast molecular motor proteins have a role in slow
      axonal transport, and the axonal transport machinery has been implicated in the
      genesis of neurodegenerative diseases.

PMID- 11595488
TI  - The balance of power in RNA trafficking.
AB  - In the past two years, several different RNA trafficking pathways have been
      characterized in oligodendrocytes; similar trafficking pathways have been
      discovered in neuronal and retroviral systems; co-assembly of multiple different
      RNAs into the same granules has been analyzed as a mechanism for coordinating
      gene expression; and a new hypothesis for RNA trafficking, based on the balance
      of power between kinesin and dynein in individual RNA granules, has been
      proposed.

PMID- 11595489
TI  - Neural stem cells.
AB  - In recent papers on neural stem cells, two areas of progress stand out. First,
      there has been a substantial growth in the published examples of
      'transdifferentiation'. Second, there has been progress, albeit more modest, in
      studies of repair by neural stem cells following transplantation into animal
      models of disease.

PMID- 11595490
TI  - Neuronal plasticity and cellular immunity: shared molecular mechanisms.
AB  - It is becoming evident that neurons express an unusual number of molecules that
      were originally thought to be specific to immune functions. One such molecule,
      class I major histocompatibility complex, is required in the activity-dependent
      refinement and plasticity of connections in the developing and adult central
      nervous system, demonstrating that molecules can perform critical roles in both
      systems. Recent studies reveal striking parallels between cellular signaling
      mechanisms in the immune and nervous systems that may provide unexpected insights
      into the development, function, and diseases of both systems.

PMID- 11595491
TI  - Imaging neural activity with temporal and cellular resolution using FISH.
AB  - Immediate early genes have gained widespread use as neural activity markers in
      studies of brain function. The recent development of cellular compartment
      analysis of temporal activity, which combines sensitive fluorescence in situ
      hybridization and laser scanning confocal microscopy, overcomes the lack of
      temporal resolution of standard methodologies and allows the tracking of distinct
      steps in the synthesis and processing of immediate early gene RNAs. Thus, this
      technique provides information about when individual neurons are activated and
      allows the visualization, within a single brain, of different neuronal
      populations engaged by two distinct experiences.

PMID- 11595492
TI  - The cell biology of Alzheimer's disease: uncovering the secrets of secretases.
AB  - Progress has been made in characterizing the secretases involved in
      endoproteolytic processing of the beta-amyloid precursor protein - the precursor
      of the amyloid beta-peptide (Abeta), which is the main constituent of amyloid
      plaques that form in the brains of patients with Alzheimer's disease. It is now
      thought that Abeta is pivotal in the pathogenesis of Alzheimer's disease, and
      that reducing brain Abeta levels may help to treat or prevent the disease. Two
      essential factors for the proteolytic generation of Abeta have been identified,
      beta-secretase and the presenilins, which might aid the design of drugs against
      this disease.

PMID- 11595494
TI  - Electron tomographic and other approaches for imaging molecular machines.
AB  - Two new methods, single-particle cryo-electron microscopy reconstruction and
      electron tomography, are increasingly used to visualize molecular machines in
      vitro and in the cellular context, respectively. Current efforts focus on the
      development of methods capable of visualizing molecular signatures in the cell,
      and first progress in this direction has now been made.

PMID- 11595495
TI  - Genetically encoded optical sensors of neuronal activity and cellular function.
AB  - Fluorescent proteins (FPs) have been engineered to produce an optical report in
      response to cellular signals. FP fluorescence can be made directly sensitive to
      the chemical environment, via specific mutations of or around the chromophore.
      Alternatively, FPs can be made indirectly sensitive to cellular signals by their
      fusion to 'detector' proteins that respond to specific cellular signals with
      structural rearrangements that act on the FP to alter fluorescence. These optical
      sensors of membrane voltage, neurotransmitter release, and intracellular
      messengers, including powerful new sensors of Ca(2+), cyclic nucleotides and
      nitric oxide, are likely to provide new insights into the workings of cellular
      signals and of information processing in neural circuits.

PMID- 11595496
TI  - Combinatorial libraries and biological discovery.
AB  - Combinatorial chemistry has become a popular tool for the preparation of
      collections of compounds that can be used to find inhibitors and substrates for
      different protein targets. It has evolved to provide small molecule libraries,
      which, with the concomittant use of affinity chromatography, gene expression
      profiling and complementation, can be used to identify compounds and their
      protein targets in biological systems, including the neurological system.

PMID- 11595497
TI  - Profiling brain transcription: neurons learn a lesson from yeast.
AB  - The application of microarray technologies to the brain poses unique challenges,
      because of the complexity of the central nervous system and the availability of
      resources. Nevertheless, recent studies using DNA chips have made inroads into
      the molecular characterization of regional and functional brain units, the
      identification of developmental gene expression patterns, and the discovery of
      transcriptional differences associated with behavioral and neuropathological
      traits.

PMID- 11595498
TI  - Complementary emerging techniques: high-resolution PET and MRI.
AB  - Noninvasive imaging technologies provide a unique window on the anatomy,
      physiology and function of living organisms. Imaging systems and methods have
      been developed for the study of small animal model systems that offer exciting
      new possibilities in neuroscience. Advances in magnetic resonance microscopy and
      positron emission tomography, and their applications in brain imaging, have
      provided many benefits to neurobiology, ranging from detailed in vivo
      neuroanatomy to the measurement of specific molecular targets.

PMID- 11595499
TI  - Imaging function in the working brain with fMRI.
AB  - The intrinsic flexibility of functional magnetic resonance imaging has allowed
      ever more innovative neuroscience applications. New acquisition and analysis
      techniques have contributed to improvements in detection sensitivity, as well as
      spatial and temporal resolution. Furthermore, by considering the dynamic
      evolution of the active brain areas in a network, computational models are making
      the first steps towards linking brain and mind.

PMID- 11595500
TI  - SNP analysis to dissect human traits.
AB  - The analysis of complex human diseases has been spurred by the number of
      published genomic sequence variants - many identified in the course of sequencing
      the human genome. But, to be useful for genetic analysis, variants have to be
      mapped accurately, their frequencies in various populations determined, and
      automated high-throughput assay techniques developed. Recently proposed methods
      address these issues: the use of 'reduced representation shotgun' methods for
      more efficient detection of single nucleotide polymorphisms (SNPs), the
      employment of high-throughput genotyping techniques, the development of SNP maps
      that incorporate information about linkage disequilibrium, and the use of SNPs in
      identifying susceptibility genes for common illnesses.

PMID- 11595501
TI  - Telomerase in endocrine and endocrine-dependent tumors.
AB  - Telomerase, the ribonucleoprotein enzyme that elongates chromosomal ends, or
      telomeres, is repressed in most normal somatic cells but reactivated in
      transformed cells to compensate for the progressive erosion of the telomeres
      during cell divisions. In accordance with this hypothesis, the presence of
      telomerase activity has been reported in more than 90% of human cancers, whereas
      most normal tissues or benign tumors contain low or undetectable telomerase
      activity. Reactivation of telomerase has also been widely reported in endocrine
      neoplasms and in hormone-related cancers. In the present study, we review the
      most recent publications on telomerase in these types of tumors. The hormonal
      regulation of telomerase activity and the possible strategies for cancer therapy
      based on the inhibition of telomerase has also been discussed.

PMID- 11595502
TI  - Familial hyperaldosteronism.
AB  - Primary aldosteronism (PAL) may be as much as ten times more common than has been
      traditionally thought, with most patients normokalemic. The study of familial
      varieties has facilitated a fuller appreciation of the nature and diversity of
      its clinical, biochemical, morphological and molecular aspects. In familial
      hyperaldosteronism type I (FH-I), glucocorticoid-remediable PAL is caused by
      inheritance of an ACTH-regulated, hybrid CYP11B1/CYP11B2 gene. Genetic testing
      has greatly facilitated diagnosis. Hypertension severity varies widely,
      demonstrating relationships with gender, affected parent's gender, urinary
      kallikrein level, degree of biochemical disturbance and hybrid gene crossover
      point position. Analyses of aldosterone/PRA/cortisol 'day-curves' have revealed
      that (1) the hybrid gene dominates over wild type CYP11B2 in terms of aldosterone
      regulation and (2) correction of hypertension in FH-I requires only partial
      suppression of ACTH, and much smaller glucocorticoid doses than those previously
      recommended. Familial hyperaldosteronism type II is not glucocorticoid
      remediable, and is clinically, biochemically and morphologically
      indistinguishable from apparently sporadic PAL. In one informative family
      available for linkage analysis, FH-II does not segregate with either the CYP11B2,
      AT1 or MEN1 genes, but a genome-wide search has revealed linkage with a locus in
      chromosome 7. As has already occurred in FH-I, elucidation of causative mutations
      is likely to facilitate earlier detection of PAL and other curable or
      specifically treatable forms of hypertension.

PMID- 11595503
TI  - No evidence for the in vivo activity of aromatase-inhibiting flavonoids.
AB  - Measurements of the aromatase-inhibiting and antioxidative capacities of
      flavonoids in vitro showed that slight changes in flavonoid structure may result
      in marked changes in biological activity. Several flavonoids such as 7
      hydroxyflavone and chrysin (5,7-dihydroxyflavone) were shown to inhibit the
      formation of 3H-17beta-estradiol from 3H-androstenedione (IC(50)<1.0 microM) in
      human choriocarcinoma JEG-3 cells and in human embryonic kidney cells HEK 293
      transfected with human aromatase gene (Arom+HEK 293). Flavone and quercetin
      (3,3',4',5,7-pentahydroxyflavone) showed no inhibition (IC(50)>100 microM). None
      of the requirements for optimal antioxidative capacity (2,3-double bond with 4'
      hydroxy group, 3-hydroxyl group, 5,7-dihydroxy structure and the orthodihydroxy
      structure in the B-ring) is relevant for the maximum inhibition of aromatase by
      flavonoids. After oral administration to immature rats at a dose of 50 mg/kg body
      weight, which considerably exceeds amounts found in daily human diets, neither
      aromatase-inhibiting nonestrogenic flavonoids, such as chrysin, nor estrogenic
      flavonoids, such as naringenin and apigenin, induced uterine growth or reduced
      estrogen- or androgen-induced uterine growth. The inability of flavonoids to
      inhibit aromatase and, consequently, uterine growth in short-term tests may be
      due to their relatively poor absorption and/or bioavailability.

PMID- 11595504
TI  - Pharmacokinetic profile of 3beta-hydroxy-17-(1H-1,2,3-triazol-1-yl)androsta-5,16
      diene (VN/87-1), a potent androgen synthesis inhibitor, in mice.
AB  - The objective of this study was to assess the pharmacokinetics and
      bioavailability of 3beta-hydroxy-17-(1H-1,2,3-triazol-1-yl)androsta-5,16-diene
      (VN/87-1) in normal male mice and in SCID mice bearing human LNCaP tumor
      xenografts. VN/87-1 is a novel potent steroidal inhibitor of human testicular 17
      alpha-hydroxylase/C(17,20)-lyase. The steroid also shows anti-androgenic activity
      and inhibits the growth of human prostate cancer cell lines (LNCaP) in vitro and
      in vivo. Male Balb/c mice were given a single oral, subcutaneous (s.c.) or
      intravenous (i.v.) bolus dose of VN/87-1 (25, 50 or 100 mg/kg). Male SCID mice
      bearing LNCaP tumor xenografts were injected with a single s.c. dose of VN/87-1
      (50 mg/kg). The animals were sacrificed at various times up to 24 h after drug
      administration and blood was collected. The plasma samples were prepared and
      analyzed by a reversed phase HPLC system equipped with a diode array detector. A
      non-compartmental pharmacokinetic approach was used to evaluate the plasma level
      versus time data. Following i.v. administration of VN/87-1, the plasma levels
      declined exponentially with an elimination half-life of 1.2+/-0.03 h. The
      absolute bioavailability of the 50 mg/kg dose after oral or s.c. administration
      was 12.08+/-2 or 57.2+/-4.5%, respectively. VN/87-1 is a high clearance (5.0+/
      1.3 l/h per kg) compound in mice and its volume of distribution was relatively
      large (6.5+/-1.2 l/kg). The pharmacokinetic parameters of VN/87-1 were not
      significantly altered in SCID mice bearing human LNCaP tumor xenografts. VN/87-1
      is well absorbed from the subcutaneous site compared with absorption from the
      gastrointestinal tract and shows linear kinetics at doses up to 100 mg/kg.

PMID- 11595505
TI  - Increased adrenal steroid secretion in response to CRF in women with hypothalamic
      amenorrhea.
AB  - OBJECTIVE: To evaluate adrenal steroid hormone secretion in response to
      corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women
      with hypothalamic amenorrhea. DESIGN: Controlled clinical study. SETTING:
      Department of Reproductive Medicine and Child Development, Section of Gynecology
      and Obstetrics, University of Pisa, Italy. PATIENT(S): Fifteen women with
      hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women
      were used as control group. INTERVENTION(S): Blood samples were collected before
      and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic
      ACTH (0.25 mg iv). MAIN OUTCOME MEASURE(S): Plasma levels of ACTH, 17
      hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17
      hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and
      androstenedione (A). RESULT(S): Basal plasma concentrations of ACTH, cortisol, 11
      deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in
      controls, whereas plasma levels of progesterone and 17-OHP were significantly
      lower in patients than in controls. In amenorrheic women the ratio of 17
      OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly
      higher than in controls, while a significant reduction in the ratio of 17
      OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to
      corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11
      deoxycortisol, DHEA and androstenedione were significantly lower in patients than
      in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP,
      androstenedione and androstenedione/cortisol were significantly higher in
      patients than in controls. CONCLUSIONS: Patients suffering for hypothalamic
      amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA)
      axis, as shown by the higher basal levels and by augmented adrenal hormone
      response to corticotropin-releasing factor administration. These data suggest a
      possible derangement of adrenal androgen enzymatic pathway.

PMID- 11595506
TI  - The effect of the arylhydrocarbon receptor on the human steroidogenic acute
      regulatory gene promoter activity.
AB  - The steroidogenic acute regulatory (StAR) protein is a rate-limiting factor in
      steroid hormone production. The StAR protein plays a role in the movement of
      cholesterol from the outer membrane to the inner membrane, where cholesterol side
      chain cleavage enzyme exists. Dioxins, which may act as 'endocrine disruptors',
      mimic and antagonize endogenous hormone actions in vivo. Although the mechanism
      of endocrine disruption is not clear, the actions of dioxins are known to be
      mediated by binding to the arylhydrocarbon receptor (AhR), and it is known that
      dioxins act as transcription factors to endocrine-associated gene expression. In
      the present study, we examined the effect of the AhR on the human StAR gene
      promoter, and we clarified the action mechanisms of environmental endocrine
      disruptors. We transfected constructs containing the human StAR gene promoter
      sequences pGL(2) 1.3-kb StAR (nt -1293 to +39) into mouse Y-1 adrenal tumor cells
      and measured the promoter activity of the StAR gene. With the addition of beta
      napthoflavone (betaNF), which is a ligand of AhR, to the culture medium, the
      activity of the StAR gene promoter increased significantly (P<0.05), and with the
      addition of 1 microM of betaNF, it became maximum (3.1+/-0.6-fold higher than the
      control value). When the AhR and ARNT were co-transfected together in Y-1 cells
      or human adrenocortical carcinoma H295R cells, the promoter activity of the StAR
      gene significantly (P<0.05) increased, to a level 1.4+/-0.01-fold higher in Y-1
      cells and to a level 1.6+/-0.04-fold higher in H295R cells than the control
      level, when 1 microM of betaNF was added. We examined the effect of induction of
      cAMP with transfection with AhR or ARNT. With the addition of 1 mM 8-Br-cAMP,
      there were no differences between the StAR gene promoter activities in the group
      in which AhR and ARNT was introduced and in the group in which they were not
      introduced. The results suggest that AhR plays a role in the promoter activity of
      the human StAR gene and that the effect of AhR on StAR gene expression may cause
      a disturbance to the human endocrine system.

PMID- 11595507
TI  - Characterization of PGE(2) receptors (EP) and their role as mediators of
      1alpha,25-(OH)(2)D(3) effects on growth zone chondrocytes.
AB  - Growth plate chondrocyte function is modulated by the vitamin D metabolite
      1alpha,25-(OH)(2)D(3) via activation of protein kinase C (PKC). In previous
      studies with cells derived from prehypertrophic and upper hypertrophic zones of
      rat costochondral cartilage (growth zone cells), inhibition of prostaglandin
      production with indomethacin caused a decrease in the stimulation of PKC
      activity, suggesting that changes in prostaglandin levels mediate the 1alpha,25
      (OH)(2)D(3)-dependent response in these cells. Growth zone cells also respond to
      PGE(2) directly, indicating that prostaglandins act as autocrine or paracrine
      regulators of chondrocyte metabolism in the growth plate. The aim of the present
      study was to identify which PGE(2) receptor subtypes (EP) mediate the effects of
      PGE(2) on growth zone cells. Using primers specific for EP1-EP4, reverse
      transcription-polymerase chain reaction (RT-PCR) amplified EP1 and EP2 cDNA in a
      RT-dependent manner. In parallel experiments, we used EP subtype-specific
      agonists to examine the role of EP receptors in 1alpha,25-(OH)(2)D(3)-mediated
      cell proliferation and differentiation. 17-Phenyl-trinor-PGE(2) (PTPGE(2)), an
      EP1 agonist, decreased [3H]-thymidine incorporation in a dose-dependent manner
      and augmented the 1alpha,25-(OH)(2)D(2)-induced inhibition of [3H]-thymidine
      incorporation. PTPGE(2) also caused significant increases in proteoglycan
      production, as measured by [35S]-sulfate incorporation, and alkaline phosphatase
      specific activity. 1alpha,25-(OH)(2)D(3)-induced alkaline phosphatase activity
      was only slightly stimulated by PTPGE(2). In contrast, 1alpha,25-(OH)(2)D(3)
      induced PKC activity was synergistically increased by PTPGE(2), whereas EP1
      antagonists SC-19220 and AH6809 inhibited PKC activity in a dose-dependent
      manner. The EP2, EP3 and EP4 agonists had no effect on the various cell-induced
      responses measured. EP1 receptor-induced responses were blocked by the
      phospholipase C inhibitor U73122, and reduced by PKA inhibitors. EP1 receptor
      induced PKC activity was insensitive to pertussis toxin or choleratoxin but
      blocked by the G-protein inhibitor GDPbetaS, suggesting the involvement of G(q).
      These results suggest that the EP1 receptor subtype mediates various PGE(2)
      induced cellular responses in growth zone chondrocytes leading to decreased
      proliferation and enhanced differentiation, as well as the effect of 1alpha,25
      (OH)(2)D(3) on cellular maturation.

PMID- 11595508
TI  - Stable expression of human 5alpha-reductase type II in COS1 cells due to
      chromosomal gene integration: a novel tool for inhibitor identification.
AB  - Inhibitors of human 5alpha-reductase type II are promising drug candidates for
      the treatment of benign prostatic hyperplasia which is associated with high
      prostatic DHT levels. In this study we describe the evaluation of potential
      inhibitors in a new cell assay. First a plasmid (pRcCMV-5alphaII) for the
      expression of human 5alpha-reductase type II was constructed by the use of the
      vector pRcCMV and transfected into the African green monkey fibroblast-like cell
      line COS1. By selection with G418 sulfate, ten COS1 single cell clones were
      obtained of which three stably exhibited high 5alpha-reductase activity. One
      single cell clone (COS1-5alphaIIST) was selected for further investigations. By
      Southern blot analysis, fluorescence in situ hybridization (FISH) and comparative
      PCR experiments it turned out that the expression plasmid pRcCMV-5alphaII has
      been integrated into the chromosome, resulting in a long-term stable expression
      of the foreign 5alpha-reductase gene. The newly established cell line was used
      for testing novel compounds on their inhibitory effect on human 5alpha-reductase
      type II. Using this whole cell assay, inhibitors with IC(50) values in the
      nanomolar range could be identified.

PMID- 11595509
TI  - Ovarian hormone receptors in human mammary stromal cells.
AB  - Mesenchymal cells of the rodent breast express both estrogen and progesterone
      receptors. Searches for these molecules in the human breast have yielded
      conflicting results. Following immunohistochemical staining of samples of normal
      human breast tissue, the authors detected estrogen receptor alpha protein and
      progesterone receptor protein in extralobular (non-specialized) fibroblasts and
      estrogen receptor alpha protein in adipocytes. Tissues from young teenage girls
      and pregnant women contained the greatest number of receptor positive
      fibroblasts. These observations confirm prior reports of the presence of ovarian
      hormone receptors in mammary fibroblasts. The findings also illustrate
      similarities in the organization of the rodent and human breasts and thereby
      suggest that regulation of the gland by ovarian hormones involves similar
      mechanisms in both species.

PMID- 11595510
TI  - Estrogen-like activity of glabrene and other constituents isolated from licorice
      root.
AB  - Licorice root extract and its major isoflavan, glabridin, exhibited varying
      degrees of estrogen receptor (ER) agonism in different tissues in vitro and in
      vivo. Animals fed with licorice extract, compared with estradiol and glabridin,
      showed an increase in creatine kinase (CK) activity, a known marker for estrogen
      responsive genes, which was higher than expected from the levels of glabridin in
      the extract. This led us to test for other components that may contribute to this
      strong estrogen agonist activity. Results indicated that glabrene and
      isoliquiritigenin, (2',4',4-three hydroxy chalcone) (ILC) in the licorice extract
      can bind to the human ER with higher affinity (IC50, 1 and 0.5 microM) than
      glabridin (IC50, 5 microM). The stimulatory effects of glabrene in vivo were
      tissue specific and similar to those of estradiol. The effect of increasing
      concentrations of glabrene and ILC on the growth of breast tumor cell were
      biphasic. Both showed an ER-dependent growth-promoting effect at low
      concentrations (10 nM-10 microM), and ER-independent antiproliferative activity
      at concentrations >15 microM. This is the first study to indicate that glabrene,
      an isoflavene exerted varying degrees of ER agonism in different tissues.

PMID- 11595511
TI  - Oculopharyngodistal myopathy is genetically heterogeneous and most cases are
      distinct from oculopharyngeal muscular dystrophy.
AB  - The question whether oculopharyngodistal myopathy (MIM 164310) is a distinct
      disease entity or a variant of oculopharyngeal muscular dystrophy (MIM 164300)
      persists. To answer this question, we examined five patients with the clinical
      characteristics of oculopharyngodistal myopathy for GCG expansion in poly(A)
      binding protein nuclear 1 gene (previously called poly(A)-binding protein 2), the
      causative gene defect for oculopharyngeal muscular dystrophy. Only one of our
      five patients had the significant GCG expansion. Thus, oculopharyngodistal
      myopathy is a genetically heterogeneous disorder, which includes patients with
      oculopharyngeal muscular dystrophy but, for the most part, is different
      genetically from oculopharyngeal muscular dystrophy.

PMID- 11595512
TI  - Three mouse models of muscular dystrophy: the natural history of strength and
      fatigue in dystrophin-, dystrophin/utrophin-, and laminin alpha2-deficient mice.
AB  - To optimize and evaluate treatments for muscular dystrophy, it is important to
      know the natural history of the disease in the absence of therapeutic
      intervention. Here we characterized disease progression of three mutant mouse
      strains of muscular dystrophy: mdx mice, which lack dystrophin; mdx:utrn-/- mice,
      which also lack utrophin; and dy/dy mice, which are deficient in laminin alpha2.
      Normal mice show a marked increase in forelimb strength over the first 10 weeks
      of life and little fatigue (<5%) over five consecutive strength trials. Mdx and
      mdx:utrn-/- mice demonstrate less strength then normal mice and approximately 40%
      fatigue at each age. Mdx mice become obese but mdx:utrn-/- mice do not. Dy/dy
      mice remain small and are much weaker than mdx and mdx:utrn-/- mice at all ages
      even when normalized to weight; however, they show only minimal fatigue (10%).
      This work demonstrates a distinct pattern of disease progression in each model
      and provides a foundation for assessing strategies for improving strength in each
      model.

PMID- 11595513
TI  - Non-toxic ubiquitous over-expression of utrophin in the mdx mouse.
AB  - Duchenne muscular dystrophy (DMD) is an inherited, severe muscle wasting disease
      caused by the loss of the cytoskeletal protein, dystrophin. Patients usually die
      in their late teens or early twenties of cardiac or respiratory failure. We have
      previously demonstrated that the dystrophin related protein, utrophin is able to
      compensate for the loss of dystrophin in the mdx mouse, the mouse model of the
      disease. Expression of a utrophin transgene under the control of an HSA promoter
      results in localization of utrophin to the sarcolemma and prevents the muscle
      pathology. Here we show that the over-expression of full-length utrophin in a
      broad range of tissues is not detrimental in the mdx mouse. These findings have
      important implications for the feasibility of the up-regulation of utrophin in
      therapy for DMD since they suggest that tissue specific up-regulation may not be
      necessary.

PMID- 11595514
TI  - Selective changes in mitochondria respiratory properties in oxidative or
      glycolytic muscle fibers isolated from G93AhumanSOD1 transgenic mice.
AB  - Cases of familial amyotrophic lateral sclerosis (FALS) are associated with
      mutations in cytosolic copper, zinc superoxide dismutase (SOD1). Total SOD
      activity and functional mitochondrial properties were studied in muscles and
      nervous tissues of control and transgenic mice mimicking the disease. It was
      found that total SOD activity was lower in nervous tissues than in muscles in
      both transgenic and control mice. In addition SOD activity increased during
      progression of disease in muscle but not in nervous tissue of transgenic mice.
      Maximal oxygen consumption and apparent Km for ADP were decreased in mitochondria
      from transgenic soleus (an oxidative muscle). However there was no difference
      between control and transgenic mice in respiratory parameters of mitochondria in
      the EDL muscle (a glycolytic muscle). These findings indicate that oxidative
      stress due to SOD1 mutations could alter energy metabolism in FALS mice, thereby
      affecting primarily oxidative muscle of the limbs, independently of motoneuron
      loss.

PMID- 11595515
TI  - Decreased levels of myotonic dystrophy protein kinase (DMPK) and delayed
      differentiation in human myotonic dystrophy myoblasts.
AB  - Muscle cell cultures derived from a myotonic dystrophy (DM1) fetus were
      established in order to determine on the one hand, whether the differentiation of
      DM1 myoblasts is altered and, on the other hand, whether the levels of myotonic
      dystrophy protein kinase (DMPK) protein is decreased in DM1 muscle cells. DM1
      myoblasts isolated from a quadriceps of a 12-weeks old fetus proliferate at a
      similar rate as normal myoblasts isolated from a quadriceps of an unaffected 15
      weeks old fetus but their maturation is altered as shown by the decreased levels
      in slow myosin heavy chain protein. In contrast, no change was observed in the
      expression of vimentin, myogenin and embryonic myosin heavy chain. The levels of
      DMPK transcripts sharply increased during myoblast differentiation and the mutant
      DMPK transcripts are retained in discrete foci in the nuclei of muscle cells. The
      levels of 85-kDa DMPK protein was reduced by about 50% in DM1 cells compared with
      normal cells. Our study demonstrates that delay in DM1 myoblast maturation is
      associated with nuclear retention of mutant DMPK transcripts and decreased levels
      of DMPK protein.

PMID- 11595516
TI  - Normal innervation and differentiation of X-linked myotubular myopathy muscle
      cells in a nerve-muscle coculture system.
AB  - To study the pathogenesis of X-linked recessive myotubular myopathy (XLMTM), we
      used a nerve-muscle coculture system which allows the reconstitution of
      functional motor units in vitro after coupling of human skeletal muscle cells
      with embryonic rat spinal cord explants. We used three skeletal muscle cell lines
      derived from subjects with known mutations in the MTM1 gene (two from embryonic
      tissues, associated with mutations predicted to give a severe phenotype, and one
      from a neonate still alive at 3 years 6 months and exhibiting a mild phenotype).
      We compared these three XLMTM muscle cell cultures with control cultures giving
      special attention to behaviour of living cocultures (formation of the myofibres,
      contractile activity, survival), expression of muscular markers (desmin,
      dystrophin, alpha-actinin, troponin-T, myosin heavy chain isoforms), and nerve
      muscle interactions (expression and aggregation of the nicotinic acetylcholine
      receptors). We were unable to reproduce any 'myotubular' phenotype since XLMTM
      muscle cells behaved like normal cells with regard to all the investigated
      parameters. Our results suggest that XLMTM muscle might be intrinsically normal
      and emphasize the possible involvement of the myotubularin-deficient motor
      neurons in the development of the disease.

PMID- 11595517
TI  - A discrepancy resolved: human satellite cells are not preprogrammed to fast and
      slow lineages.
AB  - Satellite cells from chicken and mouse muscle when differentiated in vitro have
      been shown to display a myosin heavy chain phenotype that corresponds to the
      fibre from which they originated. Indirect evidence has suggested that this might
      not be the case for human satellite cells. In the present study we have compared
      the myosin heavy chain (MHC) profile expressed by differentiated cultures of
      satellite cells isolated from single fast or slow muscle fibres. The MHC
      composition of the isolated fibres was determined by sodium dodecyl sulfate
      glycerol gel electrophoresis and Western blotting. The MHC profile expressed by
      the differentiated myotubes was identified by immunostaining using specific
      antibodies. Our results show that all human satellite cells isolated from either
      fast or slow fibres form myotubes in vitro which co-express both fast and slow
      MHCs independently of the fibre type from which they originated. These results
      confirm that human satellite cells, in contrast to those of birds and rodents,
      are not confined to distinct fast and slow lineages.

PMID- 11595518
TI  - Axon damage in CMT due to mutation in myelin protein P0.
AB  - We describe a family carrying the Thr148Met mutation in the P0 gene. Contrary to
      other neuropathies caused by myelin gene defects, no demyeliantion could be found
      in our biopsies. Based on follow up examinations, extensive morphometry and
      immunohistochemical analysis we suggest that the mild hypomyelination documented
      in our family secondarily causes axonal degeneration and axonal loss of large and
      small fibers which predominates the clinical picture.

PMID- 11595526
TI  - Viral vectors as probes to decipher brain circuitry for weight control.
AB  - Multidisciplinary research has recently identified an intrinsic appetite
      regulating network (ARN) in the hypothalamus. The idea that viruses could help to
      chart this complex network has gained impetus owing to a combination of our
      improved understanding of virology and of genetic engineering. Recently, three
      groups have employed viral vectors as probes to: (1) trace the inflow of sensory
      information from the neocortex and limbic systems to the ARN; (2) trace the
      outflow of information from the ARN to the sympathetic nervous system to monitor
      adiposity and energy expenditure; and (3) decipher the mechanisms underlying
      leptin resistance, which is responsible for environmentally based obesity.

PMID- 11595519
TI  - Valproic acid triggers acute rhabdomyolysis in a patient with carnitine
      palmitoyltransferase type II deficiency.
AB  - A 47-year-old man suffering from a bipolar disorder and intermittent
      myoglobinuria presented with acute rhabdomyolysis with renal failure after
      starting therapy with valproic acid. On morphological examination, skeletal
      muscle revealed increased lipid storage. Biochemically, decreased enzyme activity
      of carnitine palmitoyltransferase (CPT) type II with carnitine levels in the
      lower limit was found. Genetic analysis detected the common Ser113Leu
      substitution on one allele of the CPT2 gene. We conclude that valproic acid
      should be avoided in patients with CPT type II deficiency.

PMID- 11595527
TI  - A novel view of the function of pituitary folliculo-stellate cell network.

PMID- 11595538
TI  - Osteosarcoma risk in rats using PTH 1-34.

PMID- 11595539
TI  - Apoptosis induced by FasL and TRAIL/Apo2L in the pathogenesis of thyroid
      diseases.
AB  - FasL and TRAIL/Apo2L participate in cell-mediated cytotoxicity by inducing
      apoptosis in susceptible cells via respective cell surface receptors. Normal and
      neoplastic thyroid tissues are resistant to FasL-induced apoptosis but are
      sensitized by Th-1-type cytokines. In Hashimoto's thyroiditis, both FasL and its
      receptor, Fas, are strongly upregulated and their interaction leads to the
      suicidal/fratricidal death of thyrocytes. In Graves' disease, FasL expression in
      thyroid follicular cells is induced by thionamides and kills infiltrating
      lymphocytes. In this condition, Th-2-type cytokines upregulate the anti-apoptotic
      molecules FLIP and Bcl-x(L) and protect thyrocytes from apoptosis. FasL is
      expressed by neoplastic thyrocytes and induces apoptosis of infiltrating
      lymphocytes. TRAIL/Apo2L kills thyroid carcinoma cells but spares normal
      thyrocytes, thus providing a potential therapy for thyroid cancer.

PMID- 11595540
TI  - Ion-channel regulation by G proteins.
AB  - Ion channels are end-targets (effectors) in a large number of regulatory pathways
      that are initiated by G-protein-coupled neurotransmitters and hormones.
      Modulation of ion channels by G proteins can be indirect (via second messengers
      and protein kinases) or direct, via physical interactions between G-protein
      subunits and the channel protein. These direct physical interactions are the
      focus of this review. A direct regulation has been firmly established for several
      voltage-dependent Ca(2+) channels and the G-protein-activated K(+) channels. In
      these ion-channel families, the G-protein beta gamma subunits (G beta gamma) are
      the active regulators, whereas the role of the alpha subunits (G alpha) remains
      poorly understood. Accumulating evidence suggests that intricate relationships
      between the receptor, G alpha, G beta gamma and the ion channel play a major role
      in determining the specificity and magnitude of the overall regulation.

PMID- 11595541
TI  - Brassinosteroid signaling in plants.
AB  - In animals and humans, steroid hormones (SHs) regulate gene transcription via the
      binding of nuclear receptors. In addition, rapid nongenomic effects of steroids
      occur and appear to be mediated by plasma-membrane receptors. Plants also use
      steroids as signaling molecules. These brassinosteroids (BRs) show structural
      similarity to the SHs of vertebrates and insects. Plant mutants defective in
      brassinosteroid biosynthesis or perception exhibit dwarfism and reduced
      fertility, and reveal the need for BRs during growth and development. BR
      signaling in Arabidopsis thaliana and rice (Oryza sativa) - dicotyledonous and
      monocotyledonous models, respectively - is mediated by the receptor kinases BRI1
      and OsBRI1. The extracellular domain of BRI1 perceives BRs and the signal is
      mediated via an intracellular kinase domain that autophosphorylates Ser and Thr
      residues and apparently has the potential to phosphorylate other substrates. BRI1
      transduces steroid signals across the plasma membrane and mediates genomic
      effects.

PMID- 11595542
TI  - Experimental mouse genetics-- answering fundamental questions about mammary gland
      biology.
AB  - Contemporary gene-targeting techniques now make it possible to alter specific
      genes in the genome. As a result, a plethora of mouse models have been generated
      that allow researchers to dissect cell-signaling pathways involved in mammary
      gland development and in breast cancer. But what have we learned so far? What do
      these models teach us? This review presents a global picture of how the analyses
      and comparison of individual knockout mouse models provide important insights
      into basic mammary gland biology. Particular emphasis is placed upon what is
      currently known about the signaling pathways involved in the establishment of the
      mammary ductal tree, and its subsequent proliferation at pregnancy and lactation.
      In addition to these well-established pathways, we address recent data that
      describe the role of lesser-known genes in the development of the mammary
      epithelium.

PMID- 11595543
TI  - Clinical use of a growth hormone receptor antagonist in the treatment of
      acromegaly.
AB  - The elucidation of the mechanisms by which growth hormone (GH) interacts with its
      receptor has facilitated the design of compounds that function as GH-receptor
      antagonists. One such compound, B2036, has been conjugated to polyethylene glycol
      to produce a drug, pegvisomant, that has a powerful ability to lower circulating
      concentrations of insulin-like growth factor I (IGF-I), the principal mediator of
      GH action, in patients with acromegaly and to improve the symptoms and signs
      associated with GH excess. This article describes the mechanism of action of GH
      receptor antagonists, reviews the preclinical and clinical data on the use of
      pegvisomant and discusses some of the challenges that lie ahead in judging the
      efficacy of a treatment that, unlike established therapies for acromegaly, does
      not aim to modify the underlying cause of acromegaly, namely excess GH secretion,
      but aims to lower serum IGF-I levels to normal.

PMID- 11595544
TI  - Insulin resistance in the HIV-lipodystrophy syndrome.
AB  - Insulin resistance is increasingly recognized among HIV-infected patients with
      fat redistribution (lipodystrophy) who are receiving highly active antiretroviral
      therapy. The mechanisms of insulin resistance in this population remain unknown,
      but could relate to a decrease in glucose transport caused by the direct effects
      of certain antiretroviral agents, such as the protease inhibitors, or to the
      effects of severe fat redistribution, including subcutaneous fat loss and
      increased visceral adiposity. Insulin resistance in patients with HIV
      lipodystrophy is associated with hyperlipidemia and impaired fibrinolysis, and
      might increase the risk of cardiovascular disease (CVD). Furthermore, insulin
      sensitizing agents might improve insulin resistance and reduce the risk of CVD in
      this population.

PMID- 11595550
TI  - Effects of agonist and antagonist muscle fatigue on muscle coactivation around
      the knee in pubertal boys.
AB  - In many activities the knee joint flexes and extends actively with the
      involvement of both knee extensor and flexor muscle groups. Consequently the
      examination of the muscle activity during reciprocal movements may provide useful
      information on the function of these two muscle groups during fatigued
      conditions. Therefore, the purpose of this study was to examine the activity of
      antagonist muscles during a reciprocal isokinetic fatigue test of the knee
      extensors and flexors. Fifteen healthy pubertal males (age 13.8+/-0.8 years)
      performed 22 maximal isokinetic concentric efforts of the knee extensors at 60
      degrees s(-1). The EMG activity of vastus medialis (VM), vastus lateralis (VL)
      and biceps femoris (BF) was recorded using surface electrodes. The motion ranged
      from 100 to 0 degrees of knee flexion. The average moment and average EMG (AEMG)
      at 10-30 degrees, 31-50 degrees, 51-70 degrees and 71-90 degrees angular position
      intervals were calculated for each repetition. Twenty efforts were further
      analyzed. Two-way repeated measures analysis of variance (ANOVA) tests indicated
      a significant decline of moment during the test (p<0.025). The VM and VL AEMG at
      longer muscle lengths increased significantly as the test progressed whereas the
      AEMG at short muscle lengths (10-30 degrees ) did not significantly change. The
      agonist AEMG of BF during the first repetition demonstrated a significant
      increase after the ninth repetition (p<0.025). The antagonist AEMG of all muscles
      did not change significantly during the test. These results indicate that there
      is consistent antagonist activity during both extension and flexion phases of an
      isokinetic reciprocal fatigue test. It can be concluded that during an isokinetic
      reciprocal fatigue test, both knee extensors and flexors are fatigued. However,
      this condition does not have a significant effect on the EMG patterns of these
      muscles when acting as antagonists during the test.

PMID- 11595551
TI  - Quantitative EMG analysis to investigate synergistic coactivation of ankle and
      knee muscles during isokinetic ankle movement. Part 1: time amplitude analysis.
AB  - Synergy generally refers to the coordinated action of several motor elements to
      produce a specific motor task, either intentionally or automatically. One example
      is motor irradiation, a sudden spread of synergistic muscular coactivation
      resulting from a forceful single joint movement. To investigate this type of
      synergy pattern, a quantitative EMG approach was employed to characterize
      explicit neuromuscular synergy in the ankle-knee complex during maximal ankle
      isokinetic contraction. In the present study, isokinetic ankle contractions, both
      dorsiflexion and plantarflexion, at four different speeds (30, 60, 120, and 240
      degrees/s) were studied in a normal adult population (N=11) to assess synergistic
      coactivation of the prime movers (tibialis anterior and gastrocnemius) and
      irradiated muscles (ipsilateral and contralateral rectus femoris and biceps
      femoris) of the ankle-knee complex. Electromyographic signals were collected with
      surface EMG electrodes and processed with traditional time-amplitude analysis to
      examine specific neural control strategies. The data generally supported several
      empirical assumptions common to neurological facilitation techniques. (1) Motor
      irradiation to the knee muscles due to ankle muscle isokinetic contraction was
      strongly directionally dependent. (2) Motor irradiation to the ipsilateral knee
      muscles due to ankle isokinetic contraction was speed dependent. (3) The prime
      movers demonstrated a similar control strategy, irrespective of different
      contraction speeds.

PMID- 11595552
TI  - Quantitative EMG analysis to investigate synergistic coactivation of ankle and
      knee muscles during isokinetic ankle movement. Part 2: time frequency analysis.
AB  - Fundamental to intralimb coordination in the lower extremity, ankle-knee synergy
      induced by motor irradiation has long been employed to secure facilitation of
      paralyzed muscles. This study, a companion research subsequent to the time
      amplitude analysis of surface electromyography in part 1, was to investigate the
      recruitment strategy of irradiated muscles and prime movers during ankle
      isokinetic contraction at different contraction speeds (30, 60, 120 and 240
      degrees/s) with time frequency analysis. The results indicated the recruitment
      strategies of the major irradiated muscles (ipsilateral rectus
      femoris/ipsilateral biceps femoris) and prime movers (anterior
      tibialis/gastrocnemius) were time-dependent and significantly different in terms
      of the instantaneous median frequency. In general, the prime movers for ankle
      isokinetic concentric contraction demonstrated a similar recruitment strategy,
      irrespective of different contraction speeds. This finding is consistent with the
      idea of generalized motor programs that speed is one of the constraint parameters
      supplied to motor programs. Nevertheless, the recruitment strategies of the
      irradiated muscles were highly inconsistent, varying across trials at different
      contraction speeds, and were not relevant to those of the prime movers. In
      addition, the recruitment in the irradiated muscles seemly limited to motor units
      of low threshold, in spite of maximal voluntary contraction of the prime movers.

PMID- 11595553
TI  - Lumbar loading during lifting: a comparative study of three measurement
      techniques.
AB  - Low back loading during occupational lifting is thought to be an important
      causative factor in the development of low back pain. In order to regulate spinal
      loading in the workplace, it is necessary to measure it accurately. Various
      methods have been developed to do this, but each has its own limitations, and
      none can be considered a "gold standard". The purpose of the current study was to
      compare the results of three contrasting techniques in order to gain insight into
      possible sources of error to which each is susceptible. The three techniques were
      a linked segment model (LSM), an electromyographic (EMG)-based model, and a
      neural network (NN) that used both EMG and inertial sensing techniques. All three
      techniques were applied simultaneously to calculate spinal loading when eight
      volunteers performed a total of eight lifts in a laboratory setting. Averaged
      results showed that, in comparison with the LSM, the EMG technique calculated a
      25.5+/-33.4% higher peak torque and the NN technique a 17.3+/-10.5% lower peak
      torque. Differences between the techniques varied with lifting speed and method
      of lifting, and could be attributed to differences in anthropometric assumptions,
      antagonistic muscle activity, damping of transient force peaks by body tissues,
      and, specific to the NN, underestimation of trunk flexion. The results of the
      current study urge to reconsider the validity of other models by independent
      comparisons.

PMID- 11595554
TI  - The effects of four time-varying factors on the mean frequency of a myoelectric
      signal.
AB  - Daily activities involve dynamic muscle contractions that yield nonstationary
      myoelectric signals (MESs). The purpose of this work was to determine the
      individual effects of four time-varying factors (the number and firing rate of
      active motor units, muscle force and joint angle) on the mean frequency of a MES.
      Previous theoretical and experimental work revealed that although changes in the
      number and firing rate of active motor units contribute to the nonstationarities
      of the signal, they do not significantly affect the mean frequency. In the
      experimental work, 12 subjects performed 25 static contractions, one for each
      force (20, 30, 40, 50 and 60% of maximum voluntary contraction) and elbow joint
      angle (50, 70, 90, 110 and 130 degrees extension) combination. A MES was recorded
      from the surface of the biceps brachii during each contraction. The results
      indicated that muscle force only weakly affects the mean frequency. Also shown
      was that alteration in muscle geometry resulting from changes in elbow joint
      angle does significantly affect the mean frequency. Knowing this is important for
      the assessment of muscle fatigue during dynamic contractions.

PMID- 11595555
TI  - Influence of leg stiffness and its effect on myodynamic jumping performance.
AB  - The purposes of this study are: a) to examine the possibility of influencing the
      leg stiffness through instructions given to the subjects and b) to determine the
      effect of the leg stiffness on the mechanical power and take-off velocity during
      the drop jumps. A total of 15 athletes performed a series of drop jumps from
      heights of 20, 40 and 60 cm. The instructions given to the subjects were a) "jump
      as high as you can" and b) "jump high a little faster than your previous jump".
      The jumps were performed at each height until the athlete could not achieve a
      shorter ground contact time. The ground reaction forces were measured using a
      "Kistler" force plate (1000 Hz). The athletes body positions were recorded using
      a high speed (250 Hz) video camera. EMG was used to measure muscle activity in
      five leg muscles. The data was divided into 5 groups where group 1 was made up of
      the longest ground contact times of each athlete and group 5 the shortest. The
      leg and ankle stiffness values were higher when the contact times were shorter.
      This means that by influencing contact time through verbal instructions it is
      possible to control leg stiffness. Maximum center of mass take-off velocity the
      can be achieved with different levels of leg stiffness. The mechanical power
      acting on the human body during the positive phase of the drop jumps had the
      highest values in group 3. This means that there is an optimum stiffness value
      for the lower extremities to maximize mechanical power.

PMID- 11595556
TI  - The EMG activity and mechanics of the running jump as a function of takeoff
      angle.
AB  - To characterize the electromyographic (EMG) activity, ground reaction forces, and
      kinematics were used in the running jump with different takeoff angles. Two male
      long jumpers volunteered to perform running jumps at different approach speeds by
      varying the number of steps (from 3 to 9) in the run-up. Subject TM achieved a
      greater vertical velocity of the center of gravity (CG) at takeoff for all
      approach distances. This jumping strategy was associated with greater backward
      trunk lean at touchdown and takeoff, a lesser range of motion for the thigh
      during the support phase, more extended knee and ankle angles at touchdown, and a
      more flexed knee angle at takeoff. Accompanying these differences in kinematics,
      TM experienced greater braking impulses and lesser propulsion impulses for the
      forward-backward component of the ground reaction force. Furthermore, TM
      activated mainly the rectus femoris, vastus medialis, lateral gastrocnemius, and
      tibialis anterior, while if rarely activated the biceps femoris from just before
      contact to roughly the first two-thirds of the support phase. These results
      indicate that TM used a greater takeoff angle in the running jump because he
      enabled and sustained a greater blocking effect via the coordination patterns of
      the muscles relative to the hip, knee, and ankle joints. These findings also
      suggest that the muscle activities recorded in the present experiment are
      reflected in kinematics and kinetics. Further, the possible influence of these
      muscle activities on joint movements in the takeoff leg, and their effect on the
      vertical and/or horizontal velocity of the jump are discussed.

PMID- 11595557
TI  - Influence of memory demand and contra lateral activity on muscle activity.
AB  - Computer mouse work often includes memory demands and contra lateral activity.
      This study simulated video display unit (VDU) mouse-work and the focus was on
      forearm muscle activity as a result of standardised postural loads, memory
      demands and contra lateral activity. Surface and intramuscular electromyography
      (EMG) were recorded from the right forearm muscles during finger elevation and
      rest with and without memory demands and with and without contra lateral activity
      i.e. activity of the left hand. In most situations, memory demand increased
      activity in the m. extensor carpi radialis brevis and m. flexor digitalis
      superficialis. Also contra lateral activity increased activity in situations with
      and without memory demands. While surface EMG level of the m. extensor digitorum
      communis did not increase during memory demands, intramuscular EMG level
      increased when memory demands and contra lateral activity was combined. Influence
      of memory demands and contra lateral activity were most pronounced, in situations
      where activity levels were small. We presume that it is not only prolonged time
      of active computer mouse use that is a risk for development of musculoskeletal
      disorders, but also the time when people interact with the computer mentally or
      with the 'non-mouse hand', while resting their 'mouse-hand' on the mouse.

PMID- 11595558
TI  - Mycophenolic acid levels in pediatric heart transplant recipients receiving
      mycophenolate mofetil.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is an immunosuppressive agent that has
      shown promise in adult patients who have undergone heart transplantation. There
      have been a number of studies of the pharmacokinetics of MMF in adult solid organ
      transplant recipients, but there is very little information in the pediatric
      population. The purpose of this study was to review our experience with MMF
      dosing and the role of mycophenolic acid (MPA) levels for therapeutic drug
      monitoring in a population of pediatric heart transplant recipients. METHODS:
      Data were obtained by review of the pediatric heart transplant database between
      November 1, 1997 and October 15, 1998. The data included all serum trough MPA
      levels, patient age, weight, height, indication for and dose of MMF, other
      medications, and details of all episodes of graft rejection. RESULTS: Forty-four
      patients (27 males) had a total of 128 serum trough MPA levels. Median age at
      transplant was 2.7 years (7 days to 18.4 years), and at time of review was 6.3
      years (29 days to 23.5 years). MMF treatment was used for induction in 18
      patients, induction and rejection in 23 patients and graft vasculopathy in 3
      patients. Dosing by body surface area (mg/m(2)), age and interval from
      transplantation were all independently associated with MPA level. There was a
      trend toward requiring higher doses to achieve desired levels (>3 ng/ml) in
      younger patients. The average dose to achieve desired levels was higher in the
      immediate post-transplant period. There was a trend that MPA levels for a given
      dose were higher in patients on concurrent tacrolimus therapy. CONCLUSIONS: (1)
      There is marked individual variation in pharmacokinetics of MMF in pediatric
      patients; (2) dosing by body surface area may be advantageous; (3) higher MMF
      doses may be required at younger ages and in the early period after
      transplantation; (4) lower MMF doses may be required with concurrent tacrolimus
      therapy; and (5) serum trough MPA levels may relate to efficacy. Therefore,
      therapeutic drug monitoring of serum trough MPA levels may be required for
      individualized MMF dosing in pediatric cases.

PMID- 11595559
TI  - Bronchogenic carcinoma complicating lung transplantation.
AB  - BACKGROUND: Malignancy is a well-recognized complication of solid-organ
      transplantation. Although a variety of malignancies have been reported in lung
      transplant recipients, a paucity of information exists regarding the incidence
      and clinical course of bronchogenic carcinoma in this patient population.
      METHODS: We conducted a retrospective cohort study of our lung transplant
      experience at the University of Pennsylvania. RESULTS: We identified 6 patients
      with bronchogenic carcinoma detected at the time of, or developing after,
      transplantation. The incidence of bronchogenic carcinoma was 2.4%. All patients
      with lung cancer had a history of smoking, with an average of 79 +/- 39 pack
      years. A total of 5 patients had chronic obstructive pulmonary disease, and 1 had
      idiopathic pulmonary fibrosis. Lung cancers were all of non-small-cell histology
      and first developed in native lungs. Three patients had bronchogenic carcinoma at
      the time of surgery. The remaining 3 patients were diagnosed between 280 and
      1,982 days post-transplantation. Of the 6 patients, 4 presented with a rapid
      course suggestive of an infectious process. The 1- and 2-year survival rates
      after diagnosis were 33% and 17%, respectively. CONCLUSION: Lung transplant
      recipients are at risk for harboring or developing bronchogenic carcinoma in
      their native lungs. Rapid progression to locally advanced or metastatic disease
      commonly occurs, at times mimicking an infection. Bronchogenic carcinoma should
      be considered in the differential diagnosis of pleuroparenchymal processes
      involving the native lung.

PMID- 11595560
TI  - Lymphoproliferative disease after lung transplantation: comparison of
      presentation and outcome of early and late cases.
AB  - BACKGROUND: Post-transplantation lymphoproliferative disease (PTLD) after lung
      transplantation has not been fully characterized. In previous studies, the
      incidence has varied substantially, and most cases have been reported during the
      first year after transplantation. The purpose of this study was to review our
      center's experience with PTLD and to analyze the pattern of disease and
      determinants of outcome. METHODS: Among 494 adult lung (n = 491) or heart-lung (n
      = 3) recipients, 30 cases of PTLD were retrospectively identified. The cases were
      classified by site(s) of involvement, histology and time of onset (early, < or =1
      year, and late, >1 year after transplantation). The outcome of each case was
      ascertained, and risk factors for death were analyzed in a multivariate model.
      RESULTS: PTLD was identified in 30 (6.1%) of the recipients during 1,687 patient
      years (median 2.8 years) of follow-up. The incidence density was 1.8 cases per
      100 patient-years. Fourteen cases were diagnosed during the first year after
      transplantation, and 16 cases in subsequent years. The incidence density was
      significantly higher in the first year than in later years (3.3 cases/100 patient
      years versus 1.3 cases/100 patient years; p <.008). Presentation in the thorax
      and involvement of the allograft were significantly more common in the early
      cases (thorax: 12 of 14, 86%; allograft: 9 of 14, 64%) than in the late cases
      (thorax: 2 of 16, 12%; allograft: 2 of 16, 12%). There was no difference in
      survival after the diagnosis of PTLD between the early and late cases, but
      survival time after diagnosis was significantly longer in cases with, than those
      without, allograft involvement (median 2.6 years vs 0.2 year, respectively; log
      rank p = 0.007). The presentation and pattern of organ involvement of PTLD after
      lung transplantation is related to the time of onset. CONCLUSIONS: Disease in the
      thorax and involvement of the allograft are common in the first year after
      transplantation, but other sites, especially the gastrointestinal tract,
      predominate later. PTLD that is confined to the allograft appears to have a
      somewhat better prognosis than disease that involves other sites.

PMID- 11595561
TI  - Bronchoalveolar lavage macrophage and lymphocyte phenotypes in lung transplant
      recipients.
AB  - Recent publications have demonstrated potentially pathologic changes in
      bronchoalveolar lavage (BAL) from clinically stable lung transplant recipients
      (SLTRs), but there are few available data on alveolar macrophages (AMs). We
      formulated the hypothesis that changes in BAL AM and lymphocyte phenotypes would
      be apparent even in SLTRs.A cross-sectional study using a standardized 3 x 60 ml
      BAL, investigating lymphocyte and AM phenotypes in 19 SLTRs, 5 subjects with
      bronchiolitis obliterans syndrome (BOS) and 18 normal control volunteers. BAL
      lymphocyte and AM markers were assessed using flow cytometry. We confirmed a
      significant elevation of neutrophils in all lung transplant recipients with a
      more marked elevation in the BOS subjects. Flow-cytometric analysis showed
      increased numbers of natural killer (NK; CD56/CD16-positive) cells, increased
      CD11b- and CD11c-positive CD3 lymphocytes, increased CD8-positive lymphocytes and
      increased HLA-DR expression in CD8 cells from the lung transplant recipients,
      when compared with normals (p <.005). In contrast, the expression of a number of
      AM surface markers, associated with a range of host defense functions against
      bacteria, fungi and viruses (CD11a, CD11b, CD11c, HLA-DR, CD14), was lower in
      both SLTRs and those with BOS (p <.05). These novel findings are consistent with
      complex lymphocyte and macrophage changes that may result from clinically silent
      infection, partially suppressed rejection, or both.

PMID- 11595562
TI  - Hypotension, acidosis, and vasodilatation syndrome post-heart transplant:
      prognostic variables and outcomes.
AB  - BACKGROUND: In recent years a syndrome characterized by hypotension, acidosis,
      and vasodilatation, which we have designated HAV syndrome, has been reported to
      occur more frequently after heart transplantation (HT), but its pathogenesis is
      unknown. METHODS: We analyzed consecutive patients undergoing HT between January
      1994 and June 1998 (aged 50 +/- 8 years; 87% male; 40% African American; ischemia
      time, 190 +/- 20 minutes; given triple immunosuppression without anti-lymphocyte
      antibodies) in 2 groups: 38 (54%) who developed HAV (systemic vascular resistance
      < or = 800 dines x sec x cm(-5) and serum bicarbonate < or = 20 mEq/liter) and 32
      (46%) who did not. To identify causes of HAV, we compared 113 pre-HT donor and
      recipient variables, 28 peri-HT variables, and 46 post-HT variables between
      groups. We used Mann-Whitney, Fisher exact, and chi-squared tests to compare
      variables and to determine significance. RESULTS: Univariate analysis showed that
      HAV patients had significantly greater recipient and donor weight (p = 0.000007
      and 0.0017, respectively), longer ischemia times (p = 0.0052), pre-HT use of beta
      blockers (p = 0.009), and longer waiting times for HT (p = 0.018). African
      American patients had less HAV than Caucasians (p = 0.047). Patients with pre-HT
      mechanical circulatory assistance had less HAV than pharmacologically treated
      patients (p = 0.014). Multivariate analysis showed that recipient (p = 0.0004)
      and donor weight (p = 0.0394) and ischemia time (p = 0.0015) independently
      predicted HAV and correlated with HAV severity. Deaths at < or =30 days of HT
      occurred more in patients with (33%) than in those without (15%) HAV.
      CONCLUSIONS: (1) Hypotension, acidosis, and vasodilatation after HT are
      associated with high mortality. (2) Recipient and donor weights and ischemia time
      are independent risk factors for HAV. (3) Pre-HT mechanical circulatory
      assistance and African-American race confer protection against HAV. (4) Because
      HAV risk factors can be altered, prevention may be possible. Further study is
      needed to identify the cellular and humoral mediators of HAV.

PMID- 11595563
TI  - Immunologic events and long-term survival after combined heart and kidney
      transplantation: a 12-year single-center experience.
AB  - BACKGROUND: In this study we compare the incidence of cardiac rejection and long
      term survival after combined heart and kidney transplantation (HK) and single
      heart transplantation (H). Combined HK transplantation is a surgical option for
      patients with irreversible cardiac and renal failure. However, long-term results
      of combined HK transplantation on immunologic events and patient survival remain
      unknown. METHODS: Between 1988 and 1997, 12 consecutive patients underwent
      combined HK transplantation (HK group) at a single institution. A control group
      (H group) of 24 single heart transplant recipients operated on within the same
      period was matched for age, pre-operative pulmonary vascular resistance, hepatic
      insufficiency and gender mismatch. Recipients and donors were ABO compatible
      without HLA antigen matching. All patients received immediate triple
      immunosuppression that included cyclosporine. Because of early renal dysfunction,
      cyclosporine was switched to anti-thymocyte globulin in 5 patients from the HK
      group and in 1 patient from the H group (p = 0.01). RESULTS: Actuarial freedom
      from heart rejection at 6 months and at 1 year following transplantation averaged
      90 +/- 9% and 70 +/- 14% in the HK group, and 65 +/- 10% and 49 +/- 11% in the H
      group, respectively (p = 0.023). Actuarial survival at 1, 5 and 12 years was not
      significantly different between groups, at 66%, 55% and 28% in the HK group, and
      66%, 44% and 32% in the H group, respectively (p = 0.66). CONCLUSION: The
      incidence of cardiac rejection was significantly lower. Long-term survival in the
      HK group was similar to that in the H group. Putative mechanisms of decreased
      cardiac rejection in the HK group include allogeneic stimulation, donor-derived
      dendritic cells and induction by anti-thymocyte globulins. The need for long-term
      immunosuppression may be reduced after combined heart and kidney transplantation.

PMID- 11595564
TI  - Do vascular compartments differ in the development of chronic rejection? AT(1)
      blocker candesartan versus Ace blocker enalapril in an experimental heart
      transplant model.
AB  - BACKGROUND: Accelerated coronary artery disease (ACAD), a serious consequence
      after heart transplantation, is characterized by diffuse, concentric myointimal
      proliferation in the arteries. Increasing evidence supports the existence of a
      local renin-angiotensin system and the role of angiotensin-II in smooth muscle
      cell proliferation. We investigated the effect of angiotensin-II blocker
      candesartan and angiotensin-converting enzyme (ACE) inhibitor enalapril on
      experimental ACAD in a rat model. METHODS: After heterotopic cardiac
      transplantation (Fisher to Lewis), recipients received 20 mg/kg/day candesartan
      or 40 mg/kg/day enalapril per os. Two groups of animals received additional pre
      treatment with candesartan or enalapril 7 days before transplantation, and
      treatment was continued after grafting. All study groups including the controls
      received 3 mg/kg/day of sub-cutaneous cyclosporine for immunosuppression. A
      syngeneic group (Lewis to Lewis), serving as extra control, did not receive any
      treatment. Eighty days after grafting, we assessed the extent of ACAD in large
      and small arteries, using digitizing morphometry and expressed as mean vascular
      occlusion (MVO). RESULTS: In enalapril and candesartan pre- and post-treated
      animals, we observed significant reduction of MVO of intramyocardial arteries
      compared with the cyclosporine group (p < 0.005), to levels similar to the
      syngeneic transplants. MVO of epicardial arteries in enalapril and candesartan
      pre- or posttreated animals did not significantly differ from cyclosporine
      controls (p > 0.05). CONCLUSION: Our results support the hypothesis of 2
      proliferative compartments in the development of ACAD, with differing receptor or
      enzyme distribution: the compartment of small, intramyocardial arteries in which
      ACAD can be reduced by ACE or AT(1) blockade, and that of large, epicardial
      arteries in which inhibition fails.

PMID- 11595565
TI  - Iso-risk curves as a tool for clinical decision-making: donor factors and medical
      urgency in cardiac transplantation.
AB  - BACKGROUND; No significant improvement of overall graft survival in cardiac
      transplantation has occurred during the past decade, notwithstanding the
      identification of several prognostic donor and recipient risk factors. By
      translating multivariate results into iso-risk curves plots, stratified for
      medical urgency, we attempt to present results in a more practical manner, to be
      used as guidelines at the time of donor heart offer and of allocation. METHODS:
      We analyzed all first heart-only transplants performed in adults and carried out
      between January 1, 1997, and June 30, 1998 (N = 1120). Before transplant, 687
      patients were at home, 233 on hospital wards, and 200 on the intensive care unit.
      The overall Cox model yielded 5 independent factors associated with 1-year graft
      outcome: donor age, donor:recipient weight ratio, medical urgency, end-stage
      heart disease, and transplant country. We used the significant donor variables of
      donor age and donor:recipient weight ratio for the iso-risk curves; we calculated
      relative risks for all combinations of donor age and donor:recipient weight
      ratio. We obtained iso-risk curves by linking equal relative risks. RESULTS: All
      iso-risk curves showed that with older donor age, the donor:recipient weight
      ratio must be higher to obtain the same relative risk for all 3 medical urgency
      groups. The more urgent the heart transplant candidate, the higher the course of
      the iso-risk curve for all donor ages. CONCLUSIONS: Iso-risk curve is an elegant
      tool for presenting multivariate analyses in a more practical and patient
      oriented manner. The more understandable prognostic factors become the more
      likely we are to achieve better results in cardiac transplantation and to use
      more optimally donor hearts. As an example, we have demonstrated the interaction
      between donor age, donor:recipient size ratio, and medical urgency.

PMID- 11595566
TI  - Superior 12-hour heart preservation with pinacidil hyperpolarizing solution
      compared to University of Wisconsin solution.
AB  - BACKGROUND: novel donor heart preservation solution was formulated to produce
      hyperpolarized arrest with the potassium channel opener, pinacidil. The superior
      cardioprotective efficacy of this solution has been demonstrated previously when
      compared to University of Wisconsin solution following 4 hours of hypothermic
      ischemia. This study tested the hypothesis that pinacidil solution may extend
      preservation time and provide superior cardioprotective efficacy following 12
      hours of ischemia. METHODS: Sixteen rabbit hearts were assigned to receive either
      pinacidil solution or University of Wisconsin solution in a crystalloid-perfused
      Langendorff model. Thirty minutes of initial perfusion preceded baseline data
      acquisition. Left ventricle pressure-volume curves were generated by inflating an
      intra-ventricular latex balloon. Following cardioplegic administration, hearts
      underwent 12 hours of hypothermic storage. After 60 minutes of reperfusion, post
      ischemic data were acquired. RESULTS: Pinacidil solution demonstrated
      significantly better myocardial preservation compared to University of Wisconsin
      solution, with better recovery of developed pressure (53.0 +/- 11.1% vs 20.7 +/-
      4.3%, p = 0.017, respectively), post-ischemic coronary flow (55.3 +/- 12.6% vs
      23.9 +/- 4.3%, p = 0.034), maximum systolic dP/dT (46.4 +/- 8.3% vs 20.2 +/-
      5.1%, p = 0.018) and minimum diastolic -dP/dT (65.3 +/- 10.8% vs 20.2 +/- 5.1%, p
      = 0.002). Diastolic compliance, expressed as baseline/post-ischemic diastolic
      slope ratios, was also better preserved by pinacidil solution (0.55 +/- 0.09) vs
      University of Wisconsin solution (0.40 +/- 0.03) (p = 0.135). CONCLUSIONS: A
      novel pinacidil solution resulted in improved donor heart preservation during 12
      hours of hypothermic ischemia compared to the "gold standard," University of
      Wisconsin solution. Adopting alternative strategies of hyperpolarized arrest may
      allow extension of preservation time beyond the limits of traditional
      depolarizing solutions.

PMID- 11595567
TI  - Recipient treatment with trimetazidine improves graft function and protects
      energy status after lung transplantation.
AB  - BACKGROUND: Ischemia-reperfusion injury remains an important obstacle to
      successful lung transplantation. Trimetazidine is an anti-ischemic drug that
      restores the ability of ischemic cells to produce energy and reduces the
      generation of oxygen-derived free radicals. The aim of this study was to assess
      the protective effect of trimetazidine after prolonged ischemia in lung
      transplantation. METHODS: Rat single-lung transplantation was performed in 4
      experimental groups (n = 5 each). In all groups, transplantation was performed
      after 18 hours of cold (4 degrees C) ischemia. All donor lungs were flushed with
      low-potassium dextran-glucose (LPDG) solution that also contained 500
      microg/liter prostaglandin estradiol (E(1)). Groups studied included: Group I:
      flush solution was administered containing 10(-6) mol/liter trimetazidine (TMZ),
      neither donor nor recipient treatment given; Group II: donors were treated with 5
      mg/kg intravenous TMZ 10 minutes prior to harvest, but the flush solution did not
      contain TMZ; Group III: recipients treated with 5 mg/kg intravenous TMZ 10
      minutes before reperfusion, and flush solution contained 10(-6) mol/liter
      trimetazidine; Group IV: ischemic control group. After 2 hours of reperfusion,
      oxygenation was measured and lung tissue was frozen and assessed for adenosine
      triphosphate (ATP) content, myeloperoxidase (MPO) activity and thiobarbituric
      acid-reactive substances (TBARS). Peak airway pressure (PawP) was recorded
      throughout the reperfusion period. RESULTS: Group III showed significantly higher
      levels of ATP content (11.1 +/- 5.01 pmol vs Group I, 3.36 +/- 1.8 pmol, p =
      0.008; vs Group II, 4.7 +/- 1.9 pmol, p = 0.03; vs Group IV, 0.7 +/- 0.2 pmol, p
      = 0.008), better oxygenation (442.5 +/- 26.5 mm Hg, vs Group I, 161.06 +/- 54.5
      mm Hg; vs Group II, 266.02 +/- 76.9 mm Hg; vs Group IV, 89.4 +/- 14.7 mm Hg, p =
      0.008) and reduced lipid peroxidation (TBARS) (0.15 +/- 0.03 nmol/g; vs Group I,
      1.04 +/- 0.76 nmol/g; vs Group II, 0.69 +/- 0.4 nmol/g; vs Group IV, 2.29 +/- 0.4
      nmol/g, p = 0.008). PawP and MPO activity were comparable in the 4 study groups.
      CONCLUSION: Recipient treatment with TMZ provided significant protection of
      energy status, better oxygenation and reduced lipid peroxidation. Our data
      suggest that TMZ may be an important adjunct in the prevention of post-transplant
      lung ischemia-reperfusion injury.

PMID- 11595568
TI  - The technique for heterotopic cardiac transplantation in mice: experience of 3000
      operations by one surgeon.
AB  - INTRODUCTION: The mouse heterotopic fully vascularized cardiac transplantation
      model has come into widespread use. However, the technique is still difficult.
      Therefore, simple anastomosis was introduced. METHODS: The donor ascending aorta
      was sutured end-to-side to the recipient abdominal aorta and the donor pulmonary
      artery was anastomosed to the recipient inferior vena cava. The main point was
      only 4 stitches on 1 side between proximal and distal anastomosis of the
      recipient aorta and inferior vena cava. RESULTS: When beginners tried to perform
      the same procedure, they were able to complete the first successful procedure
      after 11 trials and achieved 90% success after 78 operations. SUMMARY: The simple
      anastomosis is safe and shortens the operation time.

PMID- 11595569
TI  - Optimization of left ventricular function with carvedilol before high-risk
      cardiac surgery.
AB  - Patients with severe left ventricular dysfunction and symptomatic heart failure
      caused by ischemic or valvular heart disease face a high morbidity and mortality
      risk from cardiac surgery. We present data showing that excellent surgical
      outcome can be achieved after pre-treatment of such patients with carvedilol.

PMID- 11595570
TI  - Indefinite allograft survival mediated by donor bone marrow is dependent on the
      presence of a functional CD95 (Fas) gene in recipients.
AB  - It is well documented that donor bone marrow in combination with peri-transplant
      anti-thymocyte globulin (ATG) administration induces transplantation tolerance in
      a variety of animal models. Our previous work showed that the ability of donor
      marrow to induce tolerance was dependent on the presence of CD95 ligand (Fas
      ligand) on the donor cells. In this study we investigate whether CD95 (Fas) on
      the recipient cells is required. By comparing skin allograft survival times
      between wild-type C57BL/6 ATG-treated recipients and C57BL/6(lpr/lpr) ATG-treated
      recipients (which do not have a functional CD95 gene), we show that donor bone
      marrow could induce indefinite transplant survival (median survival time >200
      days) only in recipients with a functional CD95 gene. Thus, we conclude that the
      CD95 ligand-CD95 apoptotic pathway plays a major role in donor bone marrow
      induced transplantation tolerance.

PMID- 11595572
TI  - NO nerves in trematodes, too! NADPH-diaphorase activity in adult Fasciolopsis
      buski.
AB  - The free radical nitric oxide (NO) is a unique molecule with an avidity to react
      with other molecules and is known to function as a neuronal messenger. This
      nitrergic transmitter with diverse functions in signal transduction, being a gas,
      is not stored in synaptic vesicles but is generated in various neuronal cells by
      a family of nitric oxide synthases (NOSs). The NADPH-d histochemical reaction is
      regarded as a selective marker for NOS in the neuronal tissue. With histochemical
      detection of NADPH-d, the presence of NOS is demonstrated in the digenetic
      trematode, Fasciolopsis buski. Strong NADPH-d staining was observed in the
      neuronal cell bodies in the two cerebral ganglia, the brain commissure and the
      nerve fibers in the main nerve cords. NADPH-d staining was also detectable in the
      innervation of the pharynx, the cirrus sac and the ventral sucker besides being
      observable sporadically in the nerve tributaries in the general parenchyma. NO
      released by the whole worm kept in PBS at 37 degrees C could also be measured
      biochemically. The NOS activity was assayed in the whole worm homogenate and also
      in the tissue homogenate containing only the anterior pre-acetabular part of the
      parasite body. The presence of NOS in this digenean parasite confirms that a
      nitrergic innervation occurs in the trematode group also as in other groups of
      exclusively parasitic helminths and that NO represents an old signal molecule in
      evolutionary scale.

PMID- 11595571
TI  - Acute quadriplegic myopathy with loss of thick (myosin) filaments following heart
      transplantation.
AB  - Acute quadriplegic myopathy with loss of thick (myosin) filaments (AQM-LTF) is an
      acute toxic myopathy observed in critically ill patients and is characterized by
      proximal or diffuse weakness of extremities and difficulty in weaning from
      mechanical ventilation. In recent years, this myopathy has been described in
      transplanted patients, although only 5 cases have been reported following heart
      transplantation. We present 3 new cases and review the previous literature. We
      conclude that the clinical picture and outcome of AQM-LTF in heart-transplanted
      patients do not differ from those observed in other critically ill patients
      (transplanted and non-transplanted). Therefore, because AQM-LTF is often
      clinically suspected muscle biopsy should be quickly performed to confirm the
      diagnosis so that physical therapy may begin as soon as possible.

PMID- 11595573
TI  - Use of variability in the stage-specific transcription levels of Plasmodium
      falciparum in the selection of target genes.
AB  - The malarial parasite Plasmodium falciparum exhibits several morphological and
      developmental stages. We have quantified the level of expression of a battery of
      genes in the ring and trophozoite stage-two of the most prominent stages in the
      erythrocytic development of the parasite. Using optimized RT-PCR, we observed
      that some of the genes show a large variation in stage-specific expression. We
      have also correlated the level of mRNA expression (of the target enzyme) to its
      metabolic requirement using specific inhibitors. This protocol gives us a handle
      to identify vulnerable target genes that could be used to develop antimalarials.

PMID- 11595574
TI  - Tegumental alterations in juvenile Schistosoma haematobium harboured in hamsters
      following artemether treatment.
AB  - We report the findings of a detailed temporal study on tegumental alterations in
      juvenile Schistosoma haematobium, induced by artemether, using scanning electron
      microscopy. Hamsters infected with S. haematobium cercariae for 28 days were
      treated intragastrically with a single dose of 300 mg/kg artemether. Groups of
      two hamsters were killed 24 h, 72 h and 7 days after treatment, and schistosomula
      were recovered from livers by perfusion and subsequent systematic examination of
      the tissue, before routinely processing for scanning electron microscopic
      examination. Most schistosomula collected 24 h after artemether administration
      showed severe tegumental damage, usually including swelling, fusion,
      vesiculation, peeling and collapse of enlarged sensory structures. After 72 h,
      tegumental damage had increased and schistosomula generally showed contraction
      with extensive swelling, erosion and peeling of the tegument. Seven days post
      treatment, severe tegumental damage was only seen in a single male specimen with
      swelling of the worm body and destruction of the oral sucker. The other
      schistosomula showed only light to moderate damage, suggesting that schistosomula
      surviving the treatment began to recover. Our findings of tegumental damage
      following artemether treatment correlate with the efficacy of this novel
      antischistosomal drug in killing the juvenile stages of S. haematobium and
      complement recent findings with S. japonicum and S. mansoni.

PMID- 11595575
TI  - Microscopy, PCR and ELISA applied to the epidemiology of amoebiasis in Greece.
AB  - Detection and differentiation between Entamoeba histolytica and E. dispar are of
      great importance both for diagnosis and epidemiological studies. The present
      study was aimed to estimate the prevalence of these species in Greece and to
      assess the performance of microscopy, ELISA and PCR in the field. Our results
      indicate that the prevalence of these parasites is very low in Greece and that
      PCR and ELISA are by far better than microscopy. When it comes to the choice
      between ELISA and PCR, it seems that in real situations the advantages of PCR are
      outweighed by those of ELISA.

PMID- 11595576
TI  - Some rare larval trematodes of prosobranch snails, Semisulcospira spp., in the
      Lake Biwa drainage system, central Japan.
AB  - A total of 17737 individuals of prosobranch snails, Semisulcospira spp., were
      collected from Lake Biwa and its tributaries, central Japan, from 1995 to 1999.
      They were examined for trematode larvae. One species of Aspidogastrea and 28
      species of Digenea were detected. This paper briefly describes five of the 28
      digeneans: a tetracotyle metacercaria from S. niponica, Cercaria A (cystophorous
      cercaria) from S. reticulata, Cercaria B (echinostomatid cercaria) from S.
      libertina, Cercaria C (magnacauda cercaria) from S. niponica and Cercaria D
      (mutabile cercarium) from S. nakasekoae. They were rare and every one of them was
      obtained from one snail only once.

PMID- 11595577
TI  - CD4+ T cells are required for HSP65 expression in host macrophages and for
      protection of mice infected with Plasmodium yoelii.
AB  - We have reported that macrophages expressing heat-shock protein 65 play an
      essential role in protection of mice infected with Plasmodium yoelii. In this
      study, we investigated the function and expression mechanism of HSP65 in
      macrophages of mice infected with P. yoelii. C57BL/6 (B6) mice are susceptible to
      infection with the lethal (L) strain but resistant to infection with the non
      lethal (NL) strain of P. yoelii. The percentage of apoptotic macrophages in mice
      infected with the L strain was higher than that in mice infected with the NL
      strain. However, the percentage was low in L strain infected mice if they
      acquired resistance to the infection by primary infection with the NL strain.
      That apoptosis was reversely correlated with HSP65 expression in splenic
      macrophages from mice infected with P. yoelii suggests HSP65 may contribute to
      protective immunity by preventing apoptosis of macrophages in malarial infection.
      Cell depletion/transfer experiments showed that CD4+ T cells, but not CD8+ T
      cells, gammadelta T cells, NK cells or NK T cells, were required for HSP65
      expression in macrophages as well as for protection of mice infected with P.
      yoelii. In conclusion, HSP65 may play a role in preventing apoptosis of
      macrophages in mice infected with P. yoelii. CD4+ T cells are required for HSP65
      expression and for protective immunity against P. yoelii infection.

PMID- 11595578
TI  - Oesophagostomum dentatum: expression patterns of enzymes involved in eicosanoid
      production.
AB  - Cytosolic and membrane-bound proteins of various stages of Oesophagostomum
      dentatum, the nodular worm of pigs, were investigated for the presence of
      lipoxygenases (LOX) and cyclooxygenases (COX) using polyclonal and monoclonal
      antibodies. Putative 12-LOX and 15-LOX, but not 5-LOX, were detected in both
      fractions of all developmental stages in the expected size range of 75 kDa, with
      an isoelectric point of 6.0-6.5. The protein could be precipitated with 50%
      ammonium sulfate, as described for mammalian LOX. An antibody directed against
      both COX isoforms and one against mammalian COX-2 detected proteins of
      approximately 70 kDa with an isoelectric point of 6.0-6.5 in the membrane-bound
      fractions of third-stage larvae and adults, but not in the fourth-stage larvae.
      Anti-COX-1 or more specific anti-COX-2 antibodies failed to detect proteins. The
      constitutive LOX expression supports the assumption that the metabolites of this
      enzyme previously detected in O. dentatum serve intrinsic functions, while the
      production of anti-inflammatory COX-products in the invasive and luminal stages
      of the parasite implies a possible role in host-parasite interactions.

PMID- 11595579
TI  - Variations in the cytomegalovirus DNA polymerase and phosphotransferase genes in
      relation to foscarnet and ganciclovir sensitivity.
AB  - BACKGROUND: Identification of human cytomegalovirus (CMV) genome variation is
      important for understanding mutations associated with drug resistance.
      OBJECTIVES: To investigate the CMV resistance to foscarnet (PFA) and ganciclovir
      (GCV) in patients treated with antiviral drugs and to identify the DNA polymerase
      (UL54) and phosphotransferase (UL97) gene mutations inducing resistance. STUDY
      DESIGN: Antiviral susceptibility of CMV strains/isolates for PFA and GCV was
      compared by plaque reduction assay and in situ ELISA. UL54 and UL97 gene
      mutations were identified by sequencing. Growth phenotype of two CMV recombinants
      with mutations in UL54 was studied. RESULTS: Six of seven GCV resistant strains
      had alterations within the UL97. Five of them also had alterations in the UL54
      (F412C, L802M or K513E), previously shown to induce GCV resistance. Seven
      isolates had no or reduced susceptibility to PFA, which had alterations in the
      UL54 (D588N, E756K, V781I or L802M). By in vitro mutagenesis, it was shown that a
      mutation at codon D588N of UL54 conferred 9-fold reduced susceptibility to PFA,
      while a mutation at codon V781I induced 4-fold reduced susceptibility to PFA and
      GCV. Both recombinants showed the same kinetics of protein expression (IE, E, and
      L antigen) and virus yields as the CMV Towne strain. CONCLUSIONS: The
      recombinants containing alterations within the UL54 (D588N and V781I) showed a
      reduced susceptibility to antiviral drugs but no change in the replication rate
      compared to the CMV Towne.

PMID- 11595580
TI  - Non-radioactive digoxigenin DNA labeling and immunologic detection of HSV PCR
      products.
AB  - BACKGROUND: Herpes simplex virus (HSV) is a common cause of human skin and mucous
      membrane infections, and also causes sporadic meningoencephalitis. As a new
      method for rapid HSV diagnostics, polymerase chain reaction (PCR) has been
      introduced in clinical laboratories. Radioactive labeling of DNA probes has
      become a common practice in experimental laboratories. To avoid radioactive
      labeling of HSV oligonucleotide probes or PCR products, non-radioactive
      compounds, which are easily detected by enzyme or immunoassay techniques, are
      introduced. OBJECTIVES: The aim of our study was (1) to introduce non-radioactive
      labeling of HSV DNA probe by digoxigenin-labeled dUTP; (2) to establish a rapid
      and reliable laboratory method for rapid HSV diagnostics; (3) to compare the PCR
      method with the standard virology techniques, such as cell culture virus
      isolation and HSV direct fluorescent antibody test (DFA). STUDY DESIGN: We have
      tested the efficiency of PCR method and non-radioactive labeling of HSV DNA probe
      for detection of HSV from 30 clinical specimens (skin and mucous membrane swabs).
      HSV was detected in the specimens by standard virology techniques and PCR.
      Replicated HSV DNA was non-radioactively labeled by random incorporation of
      digoxigenin-labeled deoxyuridine triphosphate (DIG-dUTP), and the hybrids were
      detected by the antibody conjugates and the appropriate enzyme-mediated staining
      reaction (DIG DNA labeling and detection kit non-radioactive, Boehringer Mannheim
      GmbH). RESULTS: Non-radioactive labeling of hybridization DNA probes with
      digoxigenin-dUTP was obtained. HSV DNA was successfully multiplied and detected
      in the HSV-infected cell culture supernatant; however, it was not detected in the
      clinical specimen supernatant or sediment. HSV DNA was detected by direct PCR
      method in non-centrifugated clinical specimens. CONCLUSIONS: The PCR method could
      be successfully used for diagnoses of HSV infections. Since the sensitivity of
      this method is partly limited by the virus quantity in the specimen, we recommend
      cultivating the virus in the cell culture at least 24 h prior to PCR. The use of
      non-radioactive labeling of hybridization DNA probes, such as random primed DNA
      labeling with digoxigenin-dUTP, has proven both sensitive and specific, and more
      appropriate for diagnostic purposes than radioactive DNA labeling to be used
      until standardized commercial tests appear.

PMID- 11595581
TI  - The association of rubella virus in congenital cataract - a hospital-based study
      in India.
AB  - BACKGROUND: The association of rubella virus (RV) with congenital cataract has
      been well established. Since the data on association of RV with congenital
      cataract in India are scanty, a study was done based on virus isolation from lens
      aspirates in patients undergoing therapeutic lensectomy and serology. OBJECTIVE:
      To determine the incidence of the association of rubella virus with congenital
      cataract. STUDY DESIGN: The lens aspirates collected during the 9-year period
      (from 1990 to 1998), from 70 children up to 12 years of age with congenital
      cataract were processed for the isolation of rubella virus by conventional viral
      isolation culture method using BHK-21 and Vero cell lines. Identification of the
      virus was confirmed by immunofluorescence using human anti-rubella virus specific
      hyperimmune serum. Serum samples were collected from 55 out of these 70 children
      and the presence of antibodies to RV was detected by ELISA test. RESULTS: RV was
      isolated from lens aspirates in seven (10%) out of the 70 children with
      congenital cataract. Of the 55 sera tested, 22 had both anti-rubella IgM and IgG
      antibodies, in 13 only anti-RV IgG antibodies, in seven only IgM antibodies and
      the rest of the 13 samples did not have detectable levels of rubella antibodies.
      Among the children who had IgM antibodies, 12 (24.5%) were below the age of 6
      months. CONCLUSION: It can be concluded based on virus isolation that 10% of
      patients with congenital cataract were due to rubella infection and the detection
      of 24.5% anti-RV IgM antibodies in children below 6 months old shows the possible
      association of rubella virus with congenital cataract.

PMID- 11595582
TI  - Genotypic distribution of TT virus (TTV) in a Czech population: evidence for
      sexual transmission of the virus.
AB  - BACKGROUND: TTV is a new DNA virus distinguished by its high degree of strain
      heterogeneity. The geographic clustering of viral genotypes suggests frequent
      community transmission. While no specific human disease has yet been linked to
      it, a transmission mechanism that facilitates strain diversity may eventually
      select for a strain that will become pathogenic. OBJECTIVE: This study was
      performed to examine the prevalence, genotypic distribution, and mode of
      transmission of TTV in detail. STUDY DESIGN: Three groups of study subjects were
      recruited between October 1998 and January 2000 in Prague, Czech Republic. Group
      1 included 152 injection drug users with liver disease; group 2 included 102
      persons with liver disease who denied ever using injection drugs; group 3
      included 111 prospective blood donors. TTV DNA was detected from blood by a semi
      nested PCR assay, and a selected set of PCR products was genotyped by direct
      sequencing. Factors associated with TTV prevalence in groups 1 and 2 subjects
      were compared. RESULTS: TTV was detected in 15.8, 13.7, and 13.5% of Groups 1, 2,
      and 3 subjects, respectively (P>0.05). The most common genotype was 2 (54%),
      followed by 1 (13%). The prevalence of TTV viremia was nearly three times higher
      in persons with a present or past history of hepatitis B compared to those
      without (P<0.05). TTV prevalence increased proportionately with the number of
      lifetime sex partners in both groups (P<0.05); it was highest (32%) among non
      users of injection drugs who had five or more lifetime sex partners. CONCLUSION:
      TTV prevalence in the Czech population is similar among blood donors, persons
      with liver disease, as well as in a high-risk population of injection drug users.
      TTV appears to be sexually transmitted.

PMID- 11595583
TI  - The role of cytomegalovirus-encoded homologs of G protein-coupled receptors and
      chemokines in manipulation of and evasion from the immune system.
AB  - Cytomegaloviruses (CMVs) have the ability to persist lifelong within the infected
      host. This ability implies that these viruses are highly adapted to their hosts.
      Most importantly, they will have to employ strategies to remain hidden from the
      host's immune system. Virus genes predicted to be involved in these strategies
      include genes encoding homologs of cellular immune effector or regulatory
      proteins, such as chemokine (CK) receptor-like G protein-coupled receptors
      (GPCRs), CKs and MHC class I molecules. These genes may have been pirated by the
      virus during the long co-evolution of pathogen and host. In light of the crucial
      roles that GPCRs, CKs and MHC class I molecules play in the normal physiology of
      the host, it is to be expected that the CMV homologs of these proteins may have a
      profound impact on this physiology and, at the same time, serve vital functions
      in maintenance as well as replication of the virus within the infected host. As a
      consequence, these viral homologs can be envisaged as attractive targets for
      novel anti-viral strategies. The aim of this report is to present an overview of
      the current state of knowledge on the (putative) functions of the CMV homologs of
      GPCRs and CKs.

PMID- 11595584
TI  - Comparison of three HCV genotyping assays: a serological method as a reliable and
      inexpensive alternative to PCR based assays.
AB  - BACKGROUND: Determination of hepatitis C virus (HCV) genotypes and subtypes is of
      rising clinical importance. In times where also an increasing need for cost
      effectiveness can be observed, the demand for fast and easy performable assays
      grows. OBJECTIVES: To evaluate and compare different genotyping methods regarding
      their reliability, practicability, and expense in the daily routine. METHODS:
      Sera of 39 patients infected with different HCV subtypes were examined by a
      serological genotyping assay (NS-4 IBA), by the widely used INNO-LiPA HCV II, and
      by a nucleotide sequencing method. RESULTS: The tests performed equally well in
      terms of HCV subtyping and no different results were obtained. However, the
      serotyping assay provided the results in less than half the time needed by the
      other two assays. Significant differences were also observed regarding the 'hands
      on' times and the costs. The technical equipment which was necessary to perform
      the assays is significantly reduced using the serological assay. CONCLUSION: Our
      study demonstrates that the serological test offers the opportunity to determine
      HCV genotypes and subtypes reliably, fast, easy, and cost effective.

PMID- 11595585
TI  - Intratype HPV16 sequence variation within LCR of isolates from asymptomatic
      carriers and cervical cancers.
AB  - BACKGROUND: HPV16 is a predominant type of virus identified in genital lesions
      and strongly associated with the development of genital cancers. Infection with
      the virus is considered to be the main risk factor in the development of cervical
      cancer. Based on HPV16 DNA isolated from invasive cancers, a classification of
      intratype genetic variants was established and the strains were designated
      according to geographical regions. The HPV16 variants classification was based on
      isolates derived from cancers. OBJECTIVES: Analysis of HPV16 LCR variants
      isolated from asymptomatic carriers for comparison with cervical cancer isolates
      to examine whether a correlation can be found between cervical epithelium state
      and variant of HPV16 it carries. MATERIALS AND METHODS: The HPV16 LCR fragments
      were amplified by PCR using DNA isolated from cervical swabs and tissue sections
      then screened for nucleotide changes by SSCP. Polymorphic sites were analysed for
      regulatory protein binding properties by EMSA. RESULTS: Comparison of the two
      groups revealed that isolates from cervical cancers predominantly carry changes
      in sequences of YY1 binding sites (especially at nucleotide 7519), while variants
      from asymptomatic carriers contained nucleotide changes within or close to
      transcription binding sites for AP-1, Oct-1, NF1, Tef-1, Tef-2, Sp1, YY1 and
      viral E2. EMSA study showed that sequence changes in the segment alter binding
      and formation of transcriptional complexes in quantitative and/or qualitative
      manner and so they may inflict viral activity. CONCLUSION: The results of our
      study show that there might be HPV16 variants of decreased oncogenic potential
      therefore infection with such variants can recede.

PMID- 11595586
TI  - Comparison of a new immunochromatographic rapid test with a commercial EIA for
      the detection of Puumala virus specific IgM antibodies.
AB  - BACKGROUND: Hantaviruses are associated with two human diseases: haemorrhagic
      fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS). Puumala
      virus (PUUV), which is one of the Hantaviruses, is a causative agent of
      nephropathia epidemica (NE), a mild form of HFRS. OBJECTIVE: a new 5 min rapid
      test, POC PUUMALA (Erilab Ltd, Finland), for detecting IgM antibodies to PUUV was
      evaluated and compared with the commercially available Hantavirus (Puumala) IgM
      ELISA test (Progen, Germany). Discrepant test results between the two tests were
      confirmed by a mu-capture reference EIA. STUDY DESIGN: Two hundred and thirty
      five serum samples, which had earlier been analyzed with the Progen IgM ELISA,
      were assayed with the POC PUUMALA rapid test. Five persons, without knowing the
      Progen IgM ELISA test results, interpreted independently the rapid test results.
      In addition, a panel of 48 serum samples was analyzed in parallel with the rapid
      test and the Progen IgM ELISA by one technician in daily routine diagnostics in a
      clinical microbiology laboratory. RESULTS: the agreement between the results of
      the five interpreters was 95%, and the congruence of the results between
      individual readers and commercial ELISA test varied from 93 to 96%. Diagnostic
      efficacy of the rapid test varied between 98 and 99% compared with 96% of the
      Progen IgM ELISA. The POC PUUMALA rapid test showed higher or similar sensitivity
      compared with the Progen IgM ELISA, whereas both the tests had similar levels of
      specificity. CONCLUSIONS: the analytical performance of the POC PUUMALA rapid
      test was found to be as good or even slightly better than the analytical
      performance of the Progen IgM ELISA. In addition, the rapid and straightforward
      procedure makes the POC PUUMALA a feasible tool for the diagnosis of the acute
      PUUV infection.

PMID- 11595587
TI  - Different profiles of cytomegalovirus RNA transcripts and anti-cytomegalovirus
      IgM antibodies in renal transplant recipients.
AB  - BACKGROUND: A difference in anti-cytomegalovirus IgM antibody profile has been
      found between sera from acutely cytomegalovirus (CMV)-infected patients and sera
      from CMV-infected patients with subclinical infection. OBJECTIVES: The aim of
      this study is to investigate whether such different IgM antibody responses are
      correlated with differences in the expression of CMV immediate early and late
      mRNAs. STUDY DESIGN: We have investigated the anti-CMV IgM response in 46 renal
      transplant recipients by employing two commercially available IgM kits (AxSYM and
      IMX) as well as two novel enzyme-linked immunosorbent assays (ELISAs), which were
      developed using recombinant ppUL32 (pp150) and pUL80a (p38), respectively. The
      results were compared with four direct CMV diagnostic tests: pp65 antigenemia,
      viral culture and nucleic acid sequence-based amplification (NASBA), detecting
      either CMV immediate early 1 (IE1) mRNA (IE1-NASBA), or CMV pp67 (late) mRNA
      (pp67-NASBA). RESULTS: Analysis of all CMV-infected recipients (n=28) showed that
      in 16 recipients (group I) more than one direct test became positive after
      transplantation, while in the other 12 recipients (group II), IE1-NASBA was the
      only direct test to become positive. In group I, 100, 81, 100 and 50% of the
      recipients were IgM-positive with AxSYM, IMX, p38 and pp150, respectively. In
      group II, 100, 83, 17 and 83% of the recipients were IgM-positive with AxSYM,
      IMX, p38 and pp150, respectively. CONCLUSIONS: Our data indicate that the IgM
      response against p38 and pp150 differs significantly (P<0.01) between group I
      recipients with productive CMV infection, and group II recipients with a non
      productive CMV infection which may be of diagnostic and prognostic relevance.

PMID- 11595588
TI  - Hepatitis B virus harboring nucleotide deletions in the core promoter region and
      genotype B correlate with low viral replication activity in anti-HBe positive
      carriers.
AB  - BACKGROUND: Emergence of anti-HBe following seroconversion of HBe antigen
      indicates reduced hepatitis B virus (HBV) replication in the liver and low
      infectivity in the natural course of infection. However, some patients show
      continued replication or reactivation even in the presence of anti-HBe.
      OBJECTIVE: To clarify the cause of HBV replication, we investigated genotype
      differences and mutations in the core promoter and precore region in relation to
      virus titer. STUDY DESIGN: Using quantification of HBV DNA, nucleotide sequencing
      of the core promoter and precore region, and genotyping with the S gene by
      restriction fragment length polymorphism (RFLP), we analyzed sera of 26 anti-HBe
      positive carriers (28 serum samples). RESULTS: Various mutations were detected
      including C to T point mutation at nt 1653, A to T and G to A contiguous point
      mutations at nt 1762 and 1764 in the core promoter region, and G to A point
      mutation at nt 1896 in the precore region, but no common mutations were detected
      that were directly related to the virus titer from earlier reported mutations. In
      contrast, the mean titer of genotype B virus was 1.5 x 10(5) copies per ml and
      that of mutant HBV of genotype C having 8 base pairs (8-bp) deletion (nt 1768
      1775) in the core promoter region was 7.9 x 10(4) copies per ml (mean titer).
      These titers showed commonly lower than that of genotype C virus without 8-bp
      deletion (median titer 5.0 x 10(6) copies per ml). Transition of genotype from C
      to B after viral reactivation and reduction of proportion of 8-bp deletion mutant
      at reactivation period was observed in a patient who demonstrated exacerbation of
      liver dysfunction due to immunosuppressive therapy and increased viral
      replication. CONCLUSIONS: These results confirm those of our earlier study
      describing low replication ability of 8-bp deletion mutant HBV in vitro, and also
      indicate that the presence of genotype B correlates with reduced titer of HBV.

PMID- 11595589
TI  - CMV disease in CMV-mismatched renal transplant recipients with prophylactic low
      dose valaciclovir.
AB  - BACKGROUND: Valaciclovir (VACV) 2 g q.i.d. for 3 months after kidney
      transplantation has been shown, (Lowance et al., NEJM 1999; 340: 1462-70), to
      reduce CMV disease from 45 to 16% and rejection from 52 to 26% in CMV-negative
      (D+R-) recipients. Neurotoxic side effects, however, were frequent, and 5% of the
      patients experienced hallucinations. We hypothesised that a lower dosage of VACV
      would prevent CMV disease with fewer CNS side effects. METHODS: Since September
      1998 all CMV-mismatched renal transplant recipients received VACV 1 g t.i.d. for
      3 months posttransplantation (PT). The incidence of CMV disease, rejection and
      neurotoxic side effects during 6 months PT was studied retrospectively in, up to
      now, 25 patients. RESULTS: 24% (6/25) of the patients developed CMV disease. The
      mean time for onset of symptoms was 145 days (92-191). Five of the patients had
      mild-moderate symptoms and recovered after ganciclovir therapy for 3 weeks. One
      patient was diagnosed with a CMV-associated retinitis on day 191 PT. The rate of
      biopsy-confirmed acute graft rejection was 32% (8/25). 20% (5/25) of the patients
      had a serum creatinine of >200 micromol/l after 6 months, including one patient
      on hemodialysis. CNS adverse effects were not observed. None out of nine patients
      with basiliximab induction and VACV developed CMV disease. One patient with
      basiliximab that did not receive VACV, developed a symptomatic CMV-infection.
      CONCLUSIONS: The incidence of CMV disease was lower than in historical controls
      at our centre, and the time to onset of symptoms was prolonged. Compared to the 8
      g VACV/day study, CMV disease and graft rejection was more frequent, but no
      neurotoxic side effects were observed. A combination with basiliximab induction
      and VACV 3 g/day shows promising results, but randomised studies are needed for
      confirmation.

PMID- 11595590
TI  - Evidence for a diagnostic window in fourth generation assays for HIV.
AB  - BACKGROUND: The routine HIV screening essentially depends on the detection of HIV
      specific antibodies. However, HIV p24 antigen can be detected in individuals with
      recent HIV infection about 2-18 days prior to seroconversion. New fourth
      generation HIV screening assays combine the detection of anti-HIV antibodies with
      the simultaneous detection of HIV p24 antigen. This may result in a reduction of
      the diagnostic window after primary infection. OBJECTIVES: The performance of two
      novel fourth generation assays in routine diagnostic was evaluated. STUDY DESIGN:
      We compared two third generation, two fourth generation and one antigen HIV
      assays in a case with acute primary HIV infection. RESULTS: In our case, the HIV
      infection was detected 11 days earlier with the fourth generation assays compared
      to third generation assays. Interestingly, after the initial reactive results the
      fourth generation assays became negative resulting in a second diagnostic window.
      During this second diagnostic window neither third nor fourth generation HIV
      assays were reactive. This second diagnostic window was caused by the absence of
      HIV specific antibodies and the decline of HIV p24 antigen concentrations below
      the detection limits of the fourth generation assays. CONCLUSIONS: Fourth
      generation assays markedly improve the diagnosis of recent HIV infections but the
      possibility of a second diagnostic window must be considered.

PMID- 11595592
TI  - Genotypic analysis at multiple loci across Kaposi's sarcoma herpesvirus (KSHV)
      DNA molecules: clustering patterns, novel variants and chimerism.
AB  - BACKGROUND: The genomes of human Kaposi's sarcoma-associated herpesvirus (KSHV)
      display several levels of DNA sequence heterogeneity and subgrouping that show
      distinctive clustering patterns in related human populations. The four major
      subtype patterns for the hypervariable ORF-K1 protein correlate closely with the
      principal diasporas resulting from the migration of modern humans out of East
      Africa and suggest that KSHV is an ancient human virus that is transmitted
      primarily in a familial fashion with consequent very low recombination rates.
      However, chimeric genomes have also been detected, especially with regard to the
      presence of P versus M alleles of the ORF-K15 gene. OBJECTIVES: To understand
      further the genetic organization and evolutionary history of KSHV, especially
      with regard to possible new subtypes, recombinant genomes, constant region loci
      and clustering in particular ethnic groups or among classic versus epidemic cases
      in the same geographic area. STUDY DESIGN: Direct PCR DNA sequencing was carried
      out on the ORF-K1 and ORF-K15 genes at the extreme left and right hand sides, as
      well as on six other internal loci of diagnostic samples collected from 70 new
      KSHV-positive patients in Israel, South Korea, Sicily, Scandinavia, Brazil,
      Uganda, South Africa and the US. RESULTS AND CONCLUSIONS: Our overall results
      from more than 135 KSHV genomes from many different human population groups now
      provides evidence for seven distinct subtypes of KSHV genomes (referred to as
      A/P, B/P, C/P, D/P, M, N and Q). However, the two most closely related subtypes
      (A/P and C/P) are only differentiated at the LHS side of the genome, and the
      three most distantly related forms (M, N and Q) appear to exist only as small
      chimeric segments that are remnants from the RHS of more ancient forms of the
      virus. By analyzing multiple conserved loci across the B subtype genomes that
      predominate in sub-Saharan Africa, we can also now recognize three to four
      distinct B genome subgroups with varying patterns of inter and intratypic
      mosaicism. Analysis of classic KS genomes from Israel has revealed that the ORF
      K1 clade referred to as A1' predominates in Ashkenazi Jewish immigrants from
      Russia, whereas C2 and C6 variants predominate in North African Sephardi Jews. A
      variety of chimeric genomes containing C2 or C3 ORF-K1 genes are disseminated
      among classic KS cases throughout Europe and Asia including Israel, Sicily,
      Scandinavia, South Korea, and Taiwan. Comparison of the genomes from classic
      versus AIDS-associated KSHV in the US indicates that it was derived originally by
      reactivation and spread of a subset of the endogenous viruses carried by
      descendants of immigrants from endemic areas of Northern and Eastern Europe, the
      Mediterranean and sub-Saharan Africa.

PMID- 11595593
TI  - RT-PCR based analysis of cell culture negative stools samples from poliomyelitis
      suspected cases.
AB  - BACKGROUND: Routine diagnosis of acute flaccid paralysis (AFP) is still based on
      classical virological procedures. Several serotypes of enterovirus which possess
      the potential to cause neurological disorders are not easily isolated in the cell
      culture systems used for the AFP diagnosis. OBJECTIVES: Our goal was to look into
      the presence of enterovirus genomes in fecal suspensions previously considered
      negative by cell culture procedures, using RT-PCR. STUDY DESIGN: One hundred and
      seventy-three fecal samples collected from AFP cases and contacts occurring in
      Brazil, Peru and Bolivia and tested negative regarding viral isolation, after
      inoculation in the cell lines RD and Hep2C, were analyzed by RT-PCR using a pair
      of primers which specifically detects enterovirus genome RNA's. RESULTS: Twenty
      six samples (15%) showed amplicons compatible with those observed for enterovirus
      RNA amplification. The identity of these amplicons were confirmed by nucleotide
      sequencing. By using RT-PCR directly in the fecal suspensions we were able to
      detect enterovirus RNA's in twenty-six additional samples. These samples would be
      considered as negative if only the standard cell-culture-based methodology had
      been utilized. No polioviruses were detected among the positive samples.

PMID- 11595595
TI  - Molecular characterization of the CCR 5 gene in seronegative individuals exposed
      to human immunodeficiency virus (HIV).
AB  - BACKGROUND: Both clinical and laboratory evidence in exposed seronegative (ESN)
      individuals to human HIV-1 has suggested the existence of mechanisms of natural
      resistance to the infection. A 32 base-pair deletion in the gene that codes for
      the CCR5, which is the main coreceptor for HIV-1, confers a high degree of
      resistance to HIV-1 infection. However, the genotype Delta32/Delta32 is present
      only in 2-4% of Caucasoid ESN individuals suggesting the existence of other
      mechanisms of protection. Mutations different from Delta32 have also been
      proposed as playing a role in resistance/susceptibility to this infection.
      OBJECTIVE: To screen for different mutations along the entire coding region of
      the ccr5 gene that can potentially explain the persistent seronegativity in a
      group of ESN individuals. STUDY DESIGN: Of a total of 86 individuals analyzed for
      Delta32 mutation by the PCR technique, 36 scored HIV seropositive (SP) and 50
      were ESN. The entire group of ESN individuals was screened for other mutations in
      the ccr5 gene by single strand conformational polymorphism (SSCP) and DNA
      sequencing. RESULTS: The frequency of the mutant allele Delta32 was 4% (4/100)
      for ESN individuals and 4.2% (3/72) for SP individuals. The homozygous mutant
      genotype (Delta32/Delta32) was found in only 2% (1/50) of ESN individuals, but in
      no SP individuals. The heterozygous genotype was found in 8.3% (3/36) of SP
      individuals and in 4% (2/50) of ESN individuals. The differences in the allelic
      and genotypic frequencies among the groups were not statistically significant. A
      comparison between the observed and the expected genotypic frequencies showed
      that they were significantly different for the ESN group, suggesting a
      protective, yet indirect effect of the mutant genotype. CONCLUSIONS: The
      screening of the entire coding region of the ccr5 gene in all ESN did not
      revealed no other mutations that could account for resistance to HIV-1 infection.
      Although the CCR5 molecule is the most important coreceptor for HIV-1, mutations
      in this gene do not account for most of the cases of natural resistance to this
      virus that have so far been reported.

PMID- 11595594
TI  - Echovirus 7 associated encephalomyelitis.
AB  - BACKGROUND: Hand, foot, and mouth disease (HFMD) is endemic in Malaysia. In 1997,
      a large outbreak of enterovirus 71 (EV-71) associated HFMD resulted in 41 deaths
      due to severe left ventricular dysfunction and central nervous system infection
      with extensive damage to the medulla and pons. The clinical presentation in all
      these patients were rapid cardio-respiratory decompensation leading to cardiac
      arrest. Another large outbreak of HFMD with 55 fatal cases and a similar clinical
      picture was reported in Taiwan in 1998. In 2000, an outbreak of HFMD resulted in
      the deaths of three children who had rapid cardio-respiratory decompensation and
      one child who survived a central nervous system infection. OBJECTIVES: We set out
      to study the etiologic agent and mechanism involved in three children who
      presented to our hospital, two of whom died and one survived a central nervous
      system infection. STUDY DESIGN: The clinical course of the disease was described.
      Throat, rectal swab and cerebrospinal fluid samples were subjected to viral
      isolation and viral isolates were identified by immunofluorescence, micro
      neutralisation using human rhabdomyosarcoma (RD) cells, and reverse transcritpase
      polymerase chain reaction. Magnetic resonance imaging was performed on two of the
      patients. RESULTS: Echovirus 7 was the sole pathogen isolated from three cases of
      acute encephalomyelitis, two of which were fatal due to severe left ventricular
      dysfunction resistant to inotropic support. The survivor had residual bulbar
      palsy, but is considered to have had a good neurological outcome. CONCLUSION:
      Echovirus 7 infection associated with encephalomyelitis could be fatal due to
      indirect involvement of the heart resulting in severe left ventricular
      dysfunction. In addition one of the children presented with hand, foot, and mouth
      disease, a syndrome that has not been previously associated with echovirus 7
      infection.

PMID- 11595596
TI  - Prevalence of enteric adenoviruses among children with diarrhea in four Brazilian
      cities.
AB  - BACKGROUND: Enteric adenoviruses are related to child diarrhea and appear to be
      spread worldwide. OBJECTIVES: The aim of the present study was to determine the
      prevalence of enteric adenovirus infection among children in four Brazilian
      cities. STUDY DESIGN: stool specimens were collected from children under 5 years
      of age with acute diarrhea. RESULTS AND CONCLUSIONS: Enteric adenoviruses were
      detected in 1.55% (n=1420) of the samples analyzed indicating the circulation of
      these viruses among Brazilian children in association to diarrheal disease. These
      agents were isolated throughout the year demonstrating no specific seasonal
      distribution. Also, no pattern of serotype distribution between the cities was
      observed.

PMID- 11595597
TI  - Sexual transmission of HIV-1 isolate showing G-->A hypermutation.
AB  - Retroviral genomes with a high frequency of G-->A mutations are thought to
      originate during reverse transcription (RT). Here we present a case report of an
      AIDS patient infected with a subtype F variant where extensive G-->A
      hypermutation (G-->A Hypm) sequences were found in the protease gene. This
      patient was failing HAART at the time the hypermutation was found. These
      sequences were basically encountered in the proviral compartment on two occasions
      and were persistently absent in the plasma viral population. The patient's viral
      genotype showed several mutations related to antiretroviral drug resistance in RT
      (T69N, M184V, T215F, K219Q) and protease (M36I, G48V, I54V, T63L, V82A) genes.
      The drug regimen was changed and the viral load dropped 0.9 Logs and CD4 count
      increased by 200 cells/ml. The hypermutation was not found any more in a 1-year
      follow up. The patient's wife was infected with a similar virus strain and G-->A
      Hypm sequences were also detected in the RT gene. This is the first report of
      sexual transmitted G-->A Hypermutation in HIV-1 and suggest that this phenomenon
      can be genetically coded by the viral RT molecule.

PMID- 11595598
TI  - Comparison of methods for identifying resistant herpes simplex virus and
      measuring antiviral susceptibility.
AB  - BACKGROUND: A number of in vitro assays are used to determine susceptibility of
      HSV to antiviral agents, but results from these in vitro assays do not
      necessarily correlate with treatment outcome. OBJECTIVES: A method with improved
      capability for identifying an isolate as acyclovir (ACV) or penciclovir (PCV)
      resistant when resistance is borderline could greatly improve the management of
      HSV disease. STUDY DESIGN: A comparative evaluation of four in vitro assays,
      plaque reduction (PRA), DNA hybridization, plating efficiency (PEA) and plaque
      autoradiography (PAR) was performed to accurately identify and measure resistance
      of a TK-altered clinical HSV isolate (HSV-1 N4) from a patient who was non
      responsive to ACV treatment. Two established criteria for the prediction of
      antiviral resistance, IC(50)> or =2.0 microg/ml or an IC(50) greater than 10x
      above a sensitive virus IC(50), as well as testing in human (MRC-5) and nonhuman
      (Vero and CV-1 monkey kidney) cell lines were evaluated. RESULTS: The PRA and DNA
      hybridization assays accurately identified HSV-1 N4 as ACV(r) in human cells when
      using the 10x above sensitive virus IC(50) resistance criterion. Moreover, the
      PEA and PAR assays failed to classify HSV-1 N4 as drug resistant and indicate
      that these technologies alone are inadequate for identifying resistant virus.
      CONCLUSIONS: The data presented herein indicate that the PRA and DNA
      hybridization assays most accurately identified an otherwise borderline-resistant
      isolate as drug resistant: (i) when a sensitive virus is used within each
      individual assay as a control, (ii) when ACV and PCV susceptibility is evaluated
      in human cells, and (iii) when the 10x above sensitive IC(50) criterion is used
      to classify a virus as drug-resistant. Testing of additional clinical samples is
      warranted to further confirm these findings.

PMID- 11595599
TI  - A glossary of circulating cytokines in chronic heart failure.
AB  - Recent studies have emphasized the importance of biologically active molecules,
      termed cytokines, in the development and progression of the syndrome of chronic
      heart failure. This article summarizes a glossary of major cytokines and other
      cytokine-related inflammatory factors implicated in the pathophysiology of
      chronic heart failure, describing the source of their synthesis and factors
      regulating their secretion and analyzing their biologic effects on the
      cardiovascular system.

PMID- 11595600
TI  - Nitric oxide: not just a negative inotrope.
AB  - Nitric oxide (NO) appears to play a role in modulating cardiac function in both
      health and disease. Early studies in isolated rodent cardiac myocytes
      demonstrated a depressant effect of NO supplied by NO donors (exogenous) as well
      as NO generated within myocytes (endogenous). There is increasing evidence for a
      functional NO generating system within the human myocardium, which appears
      upregulated in certain disease states. Induction of the high output nitric oxide
      synthase isoform (iNOS) has been demonstrated in the failing myocardium, though
      its functional significance remains unproven. More recently published data have
      contradicted the notion that NO acts solely as a negative inotrope demonstrating
      positive inotropy in both isolated rodent and human ventricular myocytes in
      response to a range of NO donors. Different NO donors have different NO release
      kinetics and generate a range of NO species (NO., NO+ and NO-) which may interact
      at a number of subcellular targets. The observed response of any cardiac
      preparation to an NO donor represents the net effect of activation of different
      effector targets and may explain the contradictory reported effects of NO. To
      realise the therapeutic potential of NO will require specific targeting at a
      subcellular level.

PMID- 11595601
TI  - A new model of congestive heart failure in the mouse due to chronic volume
      overload.
AB  - OBJECTIVE: Recently, deletion of specific genes by so called knock-out techniques
      has become important for investigating the pathogenesis of various diseases. This
      form of genetic engineering is widely performed in murine models. There are,
      however, only a limited number of mouse models available in cardiovascular
      pathology. The objective of this study, therefore, was to develop a new model of
      overt congestive heart failure associated with myocardial hypertrophy in the
      mouse. METHODS: Female C57/BL6 mice weighing 19-20 g were anesthetized with
      ether. After abdominal incision, the aorta was temporarily clamped proximal to
      the renal arteries. The aorta was then punctured with a needle (outer diameter
      0.6 mm) and the needle was further advanced into the adjacent vena cava. After
      withdrawal of the needle, the aortic puncture site was sealed with cyanoacrylate
      glue. The clamp was removed, and the patency of the shunt was visually verified
      as swelling and mixing of venous and arterial blood in the vena cava. Sham
      operated mice served as controls. RESULTS: Perioperative mortality of mice with
      aortocaval shunt was 42%. Four weeks after shunt induction, mice showed a
      significant cardiac hypertrophy with a relative heart weight of 7.5+/-0.2 mg/100
      g body weight (vs. 5.1+/-0.7 mg/100 g in control mice, P<0.001). While no changes
      in blood pressure and heart rate occurred, left ventricular enddiastolic pressure
      was significantly increased in mice with shunt, and left ventricular
      contractility was impaired from 6331+/-412 to 4170+/-296 mmHg/s (P<0.05). Plasma
      concentrations of atrial natriuretic peptide (ANP) and its second messenger cGMP
      as humoral markers of heart failure as well as ventricular expression of ANP- and
      brain natriuretic peptide (BNP)-mRNA were significantly increased in mice with
      shunt compared to control mice. CONCLUSIONS: The aortocaval shunt in the mouse
      constitutes a new model of overt congestive heart failure with impaired
      hemodynamic parameters and may be a useful tool to investigate the role of
      particular genes in the development of heart failure.

PMID- 11595602
TI  - DOCA-salts induce heart failure in the guinea pig.
AB  - Heart failure (HF) is a common clinical problem confronting physicians and is
      often the final manifestation of many cardiovascular disorders. Despite recent
      advances in the pharmacological management of HF, it remains a highly lethal and
      disabling disorder. A number of animal models have been developed to study both
      the pathophysiology of HF and new therapeutic approaches to this complex
      syndrome. Only through an improved understanding of the basic biology of the
      early stages of the syndrome can HF be prevented or at least anticipated. With
      this in view, we have developed an easily realisable and inexpensive model in the
      guinea pig, which presents numerous structural, metabolic and biochemical
      similarities compared with the human heart. Thirty guinea pigs, aged 5 weeks and
      weighing 300 g were used. After anaesthesia, left nephrectomy was performed.
      After 1 week the guinea pigs were divided into: (a) control group (n=15), which
      received an injection of vehicle as well as tap water for 10 weeks; (b) DOCA
      salts group (n=15), where the animals were treated with an IM injection of 10 mg
      DOCA 5 days a week for 10 weeks and with drinking water containing 9 g/l(-1) NaCl
      and 2 g/l(-1) KCl. Our results demonstrate that the administration of DOCA-salts
      to guinea pigs for 10 weeks caused a significant increase in blood pressure
      (BP+30%) associated with left ventricular hypertrophy (LVH), evaluated by LV
      weight (+37%), LV wall (+36%), by the ratio LV weight/Body weight (+23%) and by
      an increase in LV volume (+51%). Concerning HF, the latter was clinically evident
      through an increase in body weight, heart rate and dyspnoea. Indeed, guinea pigs
      presented pleural and/or pericardial effusion often associated with ascite. This
      model, which combines pressure and volume overload, results in a slow evolution
      towards HF. This allows a better understanding of the mechanisms in early LV
      remodelling which has the potential to develop into HF. Some recent studies have
      emphasised the value of using guinea pigs. The guinea pig heart muscle presents
      two major regulatory mechanisms of contractility that are closer to those found
      in humans, the isomyosin pattern which is predominantly V(3) and the phenomenon
      of Ca(2+)-induced Ca(2+)-release from the sarcoplasmic reticulum. The DOCA-salts
      model in the guinea pig is an easy surgical procedure with high post-operative
      survival, which causes an increase in arterial BP, LVH associated with HF. This
      model is a useful tool for studying some of the basic mechanisms of
      cardiovascular diseases.

PMID- 11595603
TI  - Feasibility and accuracy of transthoracic Doppler echocardiographic estimation of
      pulmonary capillary wedge pressure applying different methods.
AB  - BACKGROUND: Pulmonary wedge pressure (PWP) is an established index of cardiac
      function and an essential component in the management of patients with congestive
      heart failure and in critically ill patients. AIM: To evaluate feasibility and
      accuracy of non-invasive prediction of PWP by Doppler echocardiography in daily
      clinical practice. METHODS: Agreement was assessed between values predicted by
      Doppler vs. invasively measured PWP. Forty-five consecutive patients [mean (S.D.)
      age 62 (10) years] with CAD (44%), DCMP (40%) and without structural heart
      disease (16%) were studied (EF< or =40% in 58% of the patients). Doppler
      transmitral and pulmonary venous flow velocity profiles were recorded. For binary
      and quantitative prediction of PWP, four different methods and five different
      linear equations, suggested previously in the literature, were evaluated.
      RESULTS: Predictive values to identify elevated PWP were highest for pulmonary
      venous flow reversal exceeding the duration of forward mitral flow during atrial
      systole (PPV 1 and NPV 0.96). Likewise, agreement with measured PWP was highest
      for equations comprising both transmitral and pulmonary venous flow variables
      (relative mean difference 0.11, S.D.+/-4.01 mmHg for the most accurate equation).
      Feasibility was slightly, but not statistically, lower when pulmonary venous flow
      was considered vs. transmitral flow parameters alone for binary prediction (87
      vs. 93%) as well as for quantitative assessment (82 vs. 93%). CONCLUSION:
      Semiquantitative prediction of elevated PWP by Doppler echocardiography is
      feasible as well as accurate in daily clinical practice. However, accuracy of
      numeric estimates is limited. Hence, invasive measurement of PWP is still
      necessary in certain clinical settings.

PMID- 11595604
TI  - Indicators of myocardial dysfunction and quality of life, one year after acute
      infarction.
AB  - BACKGROUND: There remains controversy concerning the association between
      myocardial dysfunction diagnosed soon after acute myocardial infarction (AMI),
      and subsequent quality of life. AIMS: We searched for a correlation between
      criteria of myocardial dysfunction assessed within the first month after AMI, and
      quality of life perceived 1 year later. METHODS: Six hundred and seventy-one
      patients were followed up and quality of life was assessed using the Nottingham
      Health Profile. Spearman correlation was used for univariate analyses. A logistic
      regression identified independent predictors of impaired quality of life.
      RESULTS: Patients perceiving inferior quality of life were 61% for energy, 61%
      for sleep, 49% for physical mobility, 49% for pain, 63% for emotional reactions,
      and 28% for social isolation. Impaired quality of life was not associated with
      the initial Killip class. A low ejection fraction was associated with impaired
      physical mobility (OR=1.21, 95% CI=1.05-1.39). Presence of abnormally contracting
      myocardial segments was associated with impaired mobility (1.40, 1.09-1.80) and
      with increased pain (1.30, 1.02-1.66). The presence of diseased coronary vessels
      was associated with pain (1.25, 1.06-1.46). CONCLUSION: Myocardial dysfunction
      was generally associated with impaired quality of life. This has to be considered
      when assessing improvement of quality of life after medical or surgical treatment
      of AMI.

PMID- 11595605
TI  - Prognosis of acute myocardial infarction in the thrombolytic era: medical
      evaluation is still valuable.
AB  - BACKGROUND: Modern and sophisticated technology for the management of myocardial
      infarction has progressively devalued medical evaluation. HYPOTHESIS: This study
      was undertaken to assess the importance of the findings of medical evaluation at
      hospital presentation, in patients with acute myocardial infarction. METHODS:
      Data from 590 thrombolytic-treated myocardial infarction patients were analyzed.
      The patients were grouped according to their clinical status on arrival at
      hospital. A modified Forrester classification--subset II was divided according to
      the absence (IIa) or presence (IIb) of symptoms--was applied. Short- (14 days)
      and long-term (up to 10 years) survival was analyzed and 19 independent variables
      were included in the multivariate models. RESULTS: Short-term survival was 95.6%
      for subset I, 83.3% for subset IIa, 60% for subset IIb, 54.6% for subset III, and
      34.8% for subset IV (P<0.001). By multiple regression analysis, lower clinical
      subsets (P<0.001), fewer coronary arteries with disease (P=0.006), younger age
      (P=0.014), absence of reinfarction (P=0.034), longer interval between
      streptokinase infusion and coronary arteriography (P=0.016), and higher left
      ventricular ejection fraction (P=0.037) demonstrated significant and independent
      correlation with short-term survival. Long-term survival for the total population
      was 71+/-3.6% for subset I, 54.4+/-8.5% for subset IIa, 20.8+/-9.4% for subset
      IIb, 54.5+/-15% for subset III, and 0% for subset IV (P<0.001). Using Cox
      regression analysis, lower clinical subsets (P<0.001), younger age (P<0.001),
      higher global left ventricular ejection fraction (P<0.001), and fewer coronary
      arteries with disease (P=0.021) correlated independently and significantly with
      long-term survival. When excluding data from patients who died before the short
      term follow-up (n=532), lower clinical subsets remained an important predictor of
      long-term survival (P<0.001). CONCLUSION: Clinical classification at hospital
      presentation is a powerful predictor of short- and long-term survival post
      myocardial infarction.

PMID- 11595606
TI  - Risk stratification in middle-aged patients with congestive heart failure:
      prospective comparison of the Heart Failure Survival Score (HFSS) and a
      simplified two-variable model.
AB  - AIMS: The performance of a US-American scoring system (Heart Failure Survival
      Score, HFSS) was prospectively evaluated in a sample of ambulatory patients with
      congestive heart failure (CHF). Additionally, it was investigated whether the
      HFSS might be simplified by assessment of the distance ambulated during a 6-min
      walk test (6'WT) instead of determination of peak oxygen uptake (peak VO(2)).
      METHODS AND RESULTS: In 208 middle-aged CHF patients (age 54+/-10 years, 82%
      male, NYHA class 2.3+/-0.7; follow-up 28+/-14 months) the seven variables of the
      HFSS: CHF aetiology; heart rate; mean arterial pressure; serum sodium
      concentration; intraventricular conduction time; left ventricular ejection
      fraction (LVEF); and peak VO(2), were determined. Additionally, a 6'WT was
      performed. The HFSS allowed discrimination between patients at low, medium and
      high risk, with mortality rates of 16, 39 and 50%, respectively. However, the
      prognostic power of the HFSS was not superior to a two-variable model consisting
      only of LVEF and peak VO(2). The areas under the receiver operating curves (AUC)
      for prediction of 1-year survival were even higher for the two-variable model
      (0.84 vs. 0.74, P<0.05). Replacing peak VO(2) with 6'WT resulted in a similar AUC
      (0.83). CONCLUSION: The HFSS continued to predict survival when applied to this
      patient sample. However, the HFSS was inferior to a two-variable model containing
      only LVEF and either peak VO(2) or 6'WT. As the 6'WT requires no sophisticated
      equipment, a simplified two-variable model containing only LVEF and 6'WT may be
      more widely applicable, and is therefore recommended.

PMID- 11595607
TI  - Angiotensin in cardiac surgery: efficacy in patients on angiotensin converting
      enzyme inhibitors.
AB  - BACKGROUND: Patients presenting for cardiac surgery are often treated with
      angiotensin converting enzyme inhibitors (ACEIs), either for heart failure or
      hypertension. Control of systemic vascular resistance (SVR) during surgery can be
      difficult in such patients. Angiotensin II has been available as an unlicensed
      vasoconstrictor, but there is concern about renal damage and its use. AIM: This
      study compared a standard vasoconstrictor with angiotensin II and examined the
      effect on renal function after cardiac surgery. METHOD: Twenty consecutive,
      consenting patients scheduled for cardiac surgery that had been taking ACEIs for
      at least 6 months, were randomly assigned to receive either phenylephrine or
      angiotensin II for the control of SVR during and for 24 h after cardiac surgery.
      A pulmonary artery catheter was used to guide therapy. Creatinine clearance was
      measured before, 24 and 48 h after surgery. RESULTS: Low SVR and blood pressure
      requiring intervention was seen in all patients, particularly during
      cardiopulmonary bypass. One patient in the control group failed to respond to P,
      but responded normally to angiotensin II. Neither drug caused renal impairment.
      CONCLUSION: Angiotensin II is a safe alternative to phenylephrine in patients on
      ACEIs and should be considered in patients who fail to respond to conventional
      vasoconstrictors.

PMID- 11595608
TI  - The effect of chronic digitalization on pump function in systolic heart failure.
AB  - BACKGROUND: Short- and intermediate-term use of cardiac glycosides promotes
      inotropy and improves the ejection fraction in systolic heart failure. AIM: To
      determine whether chronic digitalization alters left ventricular function and
      performance. METHODS: Eighty patients with mild-to-moderate systolic heart
      failure (baseline ejection fraction < or =45%) participated from our institution
      in a multi-center, chronic, randomized, double-blind study of digitalis vs.
      placebo. Of the 40 survivors, 38 (20 allocated to the digitalis arm and 18 to the
      placebo arm) were evaluated at the end of follow-up (mean, 48.4 months). Left
      ventricular systolic function was assessed by both nuclear ventriculography and
      echocardiography. The ejection fraction was measured scintigraphically, while the
      ventricular volumes were computed echocardiographically. RESULTS: The groups did
      not differ, at baseline or end-of-study, with respect to the ejection fraction
      and the loading conditions (arterial pressure, ventricular volumes and heart
      rate) by either intention-to-treat or actual-treatment-received analysis. Over
      the course of the trial, the digitalis arm exhibited no significant increase in
      the use of diuretics (18%, P=0.33), in distinction from the placebo group (78%,
      P=0.004), and a longer stay on study drug among those patients who withdrew from
      double-blind treatment (28.6 vs. 11.4 months, P=0.01). CONCLUSION: Following
      chronic use of digitalis for mild-to-moderate heart failure, cross-sectional
      comparison with a control group from the same inception cohort showed no
      appreciable difference in systolic function or performance. Thus, the suggested
      clinical benefit cannot be explained by an inotropic effect.

PMID- 11595609
TI  - Chronic infusion of dobutamine and nitroprusside in patients with end-stage heart
      failure awaiting heart transplantation: safety and clinical outcome.
AB  - BACKGROUND: in patients with severe heart failure additional therapeutic support
      with intravenous inotropic or vasodilator drugs is frequently employed in an
      attempt to obtain hemodynamic and clinical control. No data comparing the use and
      efficacy of chronic intravenous inotropic and vasodilator therapy in patients
      with advanced heart failure are available. AIMS: we evaluated, in a group of
      patients with advanced heart failure undergoing chronic infusion with dobutamine
      or nitroprusside, in addition to optimized oral therapy, (1) the safety of
      chronic infusion, (2) the efficacy of both drugs in managing unloading therapy
      and (3) clinical outcome of the two therapeutic strategies. METHODS: one hundred
      and thirteen patients receiving optimized oral therapy, in functional class
      III/IV with symptoms and signs of refractory heart failure and requiring
      additional pharmacological support with either intravenous dobutamine or
      nitroprusside were evaluated. Clinical and therapeutic management and clinical
      outcome of the two groups were considered. RESULTS: dobutamine was administered
      for 12 h/day for 20+/-23 days at a dosage of 7+/-3 microg/kg/min to 43 patients.
      The mean dose of nitroprusside was 0.76+/-0.99 microg/kg/min. The mean duration
      of use of this drug, administered as a 12-h/day infusion was 22+/-38 days.
      Nitroprusside infusion allowed greater doses of short-term ACE-inhibitors to be
      used compared to pre-infusion (ACE-inhibitor dose: 55+/-30 mg/day vs. 127+/-30
      mg/day P<0.0001) and during dobutamine infusion (ACE-inhibitor dose: 85+/-47
      mg/day vs. 127+/-30 mg/day P<0.002). Nitroprusside unlike dobutamine
      significantly improved the NYHA functional class. Of the 113 patients, 109 (97%)
      had a cardiac event during a mean follow-up of 337+/-264 days. Forty-four
      patients required hospitalization for worsening congestive heart failure, 45/113
      (39%) patients died during the follow-up and 27/113 (24%) patients had a heart
      transplant in status one. Hospitalization, because of worsening heart failure was
      less frequent in the nitroprusside than in the dobutamine subgroup [29/51 (57%)
      vs. 19/22 (86%) P<0.02]. The overall mortality was 28% (20/70) in the
      nitroprusside group and 58% (25/43) in the dobutamine group (odds ratio 0.33 CI
      0.16 to 0.73 P<0.006). In the group treated with nitroprusside, heart
      transplantation in status one was performed in 16/33 patients (48%), while in the
      dobutamine group this was done in 11/14 patients (78%) (odds ratio 0.25 CI 0.06
      1.02 P<0.06). There was a significant reduction in the combined end-point of
      mortality/heart transplantation in status one in patients treated with
      nitroprusside compared to those treated with dobutamine (36/70 (51%) vs. 36/43
      (84%) - (odds ratio 0.34 CI 0.14-0.80 P<0.01). The incidence of adverse events in
      the patients treated with nitroprusside was similar to that in those treated with
      dobutamine (20% vs. 17% P=ns). CONCLUSIONS: for patients awaiting heart
      transplantation chronic intermittent nitroprusside infusions are more effective
      and safer than dobutamine in relieving symptoms, facilitating unloading therapy
      management and improving survival. Whether chronic intermittent infusion of
      nitroprusside could represent a feasible medical strategy in out-patients with
      severe heart failure remains to be investigated.

PMID- 11595610
TI  - Clinical profile and management of heart failure: rural community hospital vs.
      metropolitan heart center.
AB  - BACKGROUND: Knowledge on clinical characteristics and prognosis of patients with
      heart failure originates from studies of selected populations in clinical trials
      or from epidemiological observations. Reports on the large numbers of patients
      with heart failure treated in community hospitals are sparse. OBJECTIVE: Are
      there differences in patient characteristics and heart failure management between
      a metropolitan heart center (HC) and a rural community hospital (RCH)? PATIENTS
      AND METHODS: Retrospective analysis of medical charts from all patients admitted
      for heart failure (ICD 428.x, NYHA II-IV, EF<45%) between May 1997 and April 1998
      and discharged alive from a rural community hospital. A similar, but prospective
      registry was available at the HC. Follow-up information was obtained by request
      at registration authorities. RESULTS: Patient groups comprised 120 in RCH and 146
      in HC. Mean age was 75+/-11 and 66+/-11 years, respectively (P<0.001); 48% (RCH)
      vs. 74% (HC) of patients were male (P<0.001). On admission the proportion of
      functional class IV was 69% (RCH) vs. 17% (HC) (P<0.001). At discharge, the rate
      of ACE-inhibitors was 74% (RCH) vs. 98% (HC); 11% (RCH) vs. 43% (HC) of patients
      received beta-blocker therapy. Ninety-six percent of patients in HC underwent and
      22% in RCH had undergone invasive diagnostics. One-year mortality rate of
      patients discharged alive was 26% in RCH and 19% in HC (P=n.s. after adjustment
      for age and gender). CONCLUSION: Heart failure management according to current
      guidelines, using beta-blockers and ACE inhibitors, and invasive cardiac
      examination was significantly less performed in the rural community hospital than
      in the metropolitan heart center. Therefore, strategies to improve heart failure
      management according to guidelines are urgently needed.

PMID- 11595612
TI  - Torsades de pointes caused by Mibefradil.
AB  - We report a case of symptomatic Torsades de pointes due to QTc prolongation by
      Mibefradil, which potentially explains unexpected deaths related to this drug.
      Multiple episodes of Torsades de pointes were documented in a 76-year-old woman
      with significant QTc prolongation of 0.53 s. After discontinuation of Mibefradil
      QTc intervals normalized and no further ventricular tachyarrythmias were
      observed. We conclude that Mibefradil can cause QTc prolongation and life
      threatening ventricular dysrhythmias.

PMID- 11595611
TI  - Improved outcomes from a comprehensive management system for heart failure.
AB  - AIMS: Congestive heart failure (CHF) is associated with a high readmission rate
      after diagnosis. We assessed the ability of a comprehensive management program
      (CMP) for CHF to reduce readmissions with secondary endpoints of improving
      quality of life, exercise capacity and targeted drug doses. METHODS AND RESULTS:
      Patients (pts) with: New York Heart Association Class (NYHA) III or IV CHF; left
      ventricular ejection fraction <40%; and stable outpatient therapy were assigned
      to a CMP of cardiology assessment intensive education and referral to a tailored
      exercise program. Forty-two pts (35 M, 7 F, mean age 54 years, S.D. 12 years)
      were enrolled. Two pts were transplanted, two died during follow-up and two were
      lost to follow-up. Hospital admissions were reduced by 87.2%, (mean 1.05, S.D.
      0.98, admissions per pt to mean 0.08, S.D. 0.28, admissions per pt at 6-month
      follow-up; P<0.0001). ACE-inhibitor dose increased by 42% (P<0.0008) and beta
      blocker dose increased by 61% (P<0.0001). NYHA Class, 6-min walk and quality of
      life scores all improved significantly (P<0.0001). CONCLUSION: A CMP improves QOL
      and exercise capacity as well as substantially reducing hospital admissions in
      CHF pts. This study validates the benefit of intensive outpatient care of CHF.

PMID- 11595613
TI  - Osteoprogenitor cells of mature human skeletal muscle tissue: an in vitro study.
AB  - The presence of osteogenic progenitors in human skeletal muscle is suggested by
      the formation of ectopic bone in clinical and experimental conditions, but their
      direct identification has not yet been demonstrated. The aims of this study were
      to identify osteogenic progenitor cells in human skeletal muscle tissue and to
      expand and characterize them in culture. Specimens of gracilis and semitendinosus
      muscle were obtained from young adults and digested to separate the connective
      tissue and satellite cell fractions. The cells were cultured and characterized
      morphologically and immunohistochemically using antibodies known to be reactive
      with primitive osteoprogenitor cells, pericytes, intermediate filaments, and
      endothelial cells. Alkaline phosphatase activity and osteocalcin gene expression
      were also determined. In the early stages of culture, the connective tissue cells
      obtained were highly positive for primitive osteoprogenitor cell and for pericyte
      markers. Alkaline phosphatase activity was detectable at early stages of culture
      and rose as a function of time, whereas primitive osteoprogenitor cell markers
      declined and osteocalcin mRNA expression became detectable by reverse
      transcriptase-polymerase chain reaction (RT-PCR). It is shown that human skeletal
      muscle connective tissue contains osteogenic progenitor cells. Their
      identification as pericytes, perivascular cells with established osteogenic
      potential, suggests a cellular link between angiogenesis and bone formation in
      muscle tissue. These cells are easily cultured and expanded in vitro by standard
      techniques, providing an alternative source of osteogenic progenitor cells for
      possible cell-based therapeutic use in certain conditions.

PMID- 11595614
TI  - Opposite effects of bone morphogenetic protein-2 and transforming growth factor
      beta1 on osteoblast differentiation.
AB  - Several members of the transforming growth factor-beta (TGF-beta) superfamily
      have been demonstrated to play regulatory roles in osteoblast differentiation and
      maturation, but the mechanisms by which they act on different cells at different
      developmental stages remain largely unknown. We studied the effects of TGF-beta1
      and bone morphogenetic protein-2 (BMP-2) on the differentiation/maturation of
      osteoblasts using the murine cell lines MC3T3-E1 and C3H10T1/2. BMP-2 induced or
      enhanced the expression of the osteoblast differentiation markers alkaline
      phosphatase (ALP) and osteocalcin (OC) in both cells. In contrast, TGF-beta1 was
      not only unable to induce these markers, but it dramatically inhibited BMP-2
      mediated OC gene expression and ALP activity. In addition, TGF-beta1 inhibited
      the ability of BMP-2 to induce MC3T3-E1 mineralization. TGF-beta1 did not
      sensibly modify the increase of Osf2/Cbfa1 gene expression mediated by BMP-2,
      thus demonstrating that the inhibitory effect of TGF-beta1 on osteoblast
      differentiation/maturation mediated by BMP-2 was independent of Osf2/Cbfa1 gene
      expression. Finally, it is shown that TGF-beta1 does not affect BMP-2-induced
      Smad1 transcriptional activity in the mesenchymal pluripotent cells studied
      herein. Our data indicate that in vitro BMP-2 and TGF-beta1 exert opposite
      effects on osteoblast differentiation and maturation.

PMID- 11595615
TI  - Human bone marrow stromal cells are efficiently transduced by vesicular
      stomatitis virus-pseudotyped retrovectors without affecting subsequent
      osteoblastic differentiation.
AB  - This study tested the transduction efficiency of human bone marrow stromal cells
      (hBMSCs) with vesicular stomatitis virus (VSV)-pseudotyped retrovectors and their
      subsequent osteogenic differentiation in vitro. Two different retrovectors
      encoding beta-galactosidase (beta-gal) or enhanced green fluorescent protein
      (eGFP) as marker genes were examined for transduction of hBMSCs. hBMSCs were
      obtained from bone marrow filtrates of normal donors (aged 5-35 years), cultured
      in alpha-minimal essential medium (alpha-MEM) containing 10% fetal calf serum and
      infected with retrovectors soon after the adherent cells started to form
      individual colonies. Transduced hBMSCs were observed to express eGFP protein 4-7
      days after infection in primary cultures, and the majority of hBMSCs were eGFP
      positive. hBMSCs were also stained for beta-gal in the secondary cultures and
      virtually all hBMSCs expressed beta-gal activity. Transduced hBMSCs were examined
      for their osteogenic potential. These cells were found to express markers of
      osteogenic differentiation, including alkaline phosphatase, type I collagen, bone
      sialoprotein, decorin, and osteocalcin, as strongly as uninfected control cells.
      Mineralization was also induced by dexamethasone in transduced cells as well as
      control cells. These results demonstrate that hBMSCs are highly susceptible to
      infection with VSV-pseudotyped retrovectors with the majority of cultured cells
      expressing the viral transgenes without antibiotic selection. Transduced cells
      retain their osteogenic potential in vitro. hBMSCs are a promising cellular
      vehicle for systemic human gene therapy and VSV-pseudotyped retrovectors should
      be effective for their in vitro transduction prior to cellular engraftment.

PMID- 11595616
TI  - Nitrogen-containing bisphosphonates induce apoptosis of Caco-2 cells in vitro by
      inhibiting the mevalonate pathway: a model of bisphosphonate-induced
      gastrointestinal toxicity.
AB  - Bisphosphonates have become an important addition to the pharmacological
      armamentarium against postmenopausal osteoporosis. One of the major side effects
      of oral therapy with some nitrogen-containing bisphosphonates appears to be
      gastrointestinal (GI) intolerability, particularly esophageal irritation and
      ulceration. Because nitrogen-containing bisphosphonates can cause apoptosis in a
      variety of cell types in vitro, by inhibiting the mevalonate pathway, we
      hypothesized that the effect of these agents on the GI tract may be due to
      apoptosis or inhibition of growth of gut epithelial cells. A comparison between
      clodronate, etidronate, pamidronate, alendronate, and risedronate demonstrated
      that only the nitrogen-containing bisphosphonates were effective at inducing
      apoptosis or inhibiting proliferation of Caco-2 human epithelial cells in vitro,
      at concentrations of between 10 and 1000 micromol/L. The ability of nitrogen
      containing bisphosphonates to cause apoptosis and inhibit Caco-2 cell
      proliferation was due to inhibition of the mevalonate pathway, because the
      addition of farnesol, oxidized low-density lipoprotein (LDL) cholesterol, or
      especially geranylgeraniol suppressed the effects. Furthermore, pamidronate,
      alendronate, and risedronate inhibited protein prenylation in Caco-2 cells, as
      determined by analysis of the processing of Rap1A, a prenylated small GTPase.
      These studies suggest that the effects of nitrogen-containing bisphosphonates
      observed in the GI tract may be due to inhibition of proliferation or apoptosis
      of gut epithelial cells, following loss of prenylated proteins and sterols.

PMID- 11595617
TI  - Influence of a low calcium and phosphorus diet on the anabolic effect of human
      parathyroid hormone (1-38) in female rats.
AB  - Parathyroid hormone (PTH) or synthetic N-terminal PTH fragments administered
      intermittently have been established as anabolic agents in animal and human
      bones. In the present study, the influence of a low calcium diet on the anabolic
      effect of human PTH(1-38) [hPTH(1-38)] was investigated. Forty-eight 10-week-old
      female Sprague-Dawley rats were randomly assigned to a diet with a low calcium
      content (LCa) or a diet with the recommended amount of calcium (RCa). After an
      adaptation period of 15 days, the rats were randomly assigned to hPTH(1-38)
      treatment (+LCa/+RCa) or vehicle only (-LCa/-RCa) for an additional 14 days.
      Total bone mineral density (BMD) values of several bones were determined using
      quantitative computed tomography and from ratios of ash weight to volume.
      Biomechanical competence of the fourth lumbar vertebrae and of the right femora
      was assessed. An anabolic effect could be detected in both PTH-treated groups.
      However, the bones of the +LCa group showed significantly lower BMD and also a
      diminished increase in maximal breaking force compared with those of the +RCa
      group. The study demonstrates that the anabolic effect of hPTH(1-38) is blunted
      by the LCa diet. This suggests that, during PTH treatment, dietary calcium intake
      is critical.

PMID- 11595618
TI  - Maintenance of cancellous bone in ovariectomized, human parathyroid hormone
      [hPTH(1-84)]-treated rats by estrogen, risedronate, or reduced hPTH.
AB  - This study compares effects of maintenance doses of human parathyroid hormone
      [hPTH(1-84)], 17beta-estradiol (E2), and risedronate on distal femur bone mineral
      density and proximal tibia cancellous bone histomorphometry in ovariectomized
      (ovx), osteopenic rats previously administered a higher dose of hPTH. Nine groups
      (n = 8) of 3.5-month-old ovx or intact Sprague-Dawley rats were left untreated
      for 11 weeks to allow for the development of cancellous osteopenia in the ovx
      groups. Next, the ovx rats received subcutaneous injections of hPTH (75 microg/kg
      per day, three times per week) or vehicle for 12 weeks. Treatments were then
      changed to E2 (10 microg/kg per day, two times per week), risedronate (Ris; 3
      microg/kg per day, three times per week), low-dose hPTH(1-84) (LowPTH; 25
      microg/kg per day, three times per week), or vehicle, and administered for 36
      weeks. The intact control group remained untreated for the duration of study.
      Femora and tibiae were collected at weeks -11 (baseline); 0 (ovx effect); 12
      (hPTH effect), and 24, 36, and 48 (maintenance effects). Endpoints evaluated
      included distal femur bone mineral density (BMD) and proximal tibia cancellous
      bone volume (BV/TV), osteoclast surface (Oc.S), mineralizing surface (MS),
      mineral apposition rate (MAR), and bone formation rate (BFR). Ovariectomy had a
      negative effect on distal femur BMD and proximal tibia BV/TV. Treatment of ovx
      rats with hPTH for 12 weeks resulted in higher BMD in comparison to intact
      controls, and higher cancellous BV/TV in comparison to ovx controls.
      Discontinuation of hPTH resulted in loss of gained BMD within 24 weeks and loss
      of gained BV/TV within 12 weeks. Treatment of ovx rats with hPTH for 12 weeks
      followed by E2 treatment left BMD and BV/TV similar to vehicle-treated ovx rats
      by week 48 (36 weeks after commencement of the E2 maintenance treatment).
      Maintenance treatment with risedronate resulted in BMD and BV/TV similar to that
      of intact controls. Maintenance treatment with low-dose hPTH resulted in greater
      BMD and similar BV/TV in comparison to intact controls. MS and BFR were highest
      after low-dose hPTH administration. MS and BFR were lowest after E2 or
      risedronate, whereas Oc.S was lowest after risedronate administration. Thus, in
      osteopenic rats, the increment in distal femur BMD and proximal tibia BV/TV
      gained by 12 weeks of hPTH treatment was lost within 24 and 12 weeks of treatment
      termination, respectively. Low-dose hPTH maintained BMD and BV/TV after hPTH
      treatment by stimulating bone formation, whereas risedronate maintained BMD and
      BV/TV by reducing bone resorption. E2 in a maintenance dose failed to maintain
      BMD and BV/TV after withdrawal of hPTH treatment.

PMID- 11595619
TI  - Circadian and longitudinal variation of serum C-telopeptide, osteocalcin, and
      skeletal alkaline phosphatase in C3H/HeJ mice.
AB  - Inbred strains of mice are increasingly being used as an animal model to
      investigate skeletal disorders relevant to humans. In the bone field, one of the
      most convenient endpoints for evaluating genetic, physiological, or
      pharmaceutical perturbations is the use of biochemical markers. To apply
      biochemical markers in an effective manner, it is of key importance to establish
      the biological variation and appropriate sampling time. In this study, we
      evaluate two components: (i) circadian changes, and (ii) longitudinal variation
      for three serum markers, osteocalcin, C-telopeptide, and skeletal alkaline
      phosphatase (sALP), using 6-week-old C3H/HeJ (C3H) mice. To study circadian
      rhythms, the mice were randomly divided into eight groups of 15 mice each. Blood
      was collected at 3 h intervals, starting at 9:00 A.M. and continuing until 6:00
      A.M. the next day. To determine whether circadian rhythm is intrinsically
      regulated or influenced by restricted food intake, it was also studied after a 12
      h fasting period. Serum osteocalcin and C-telopeptide levels were measured by
      enzyme-linked immunoassay (ELISA) and skeletal alkaline phosphatase by a kinetic
      assay. The results demonstrated significant circadian variations in osteocalcin
      and C-telopeptide levels with a peak value between 0900 and 1200 h during daytime
      and a nadir between 15:00 and 18:00 h. The peak levels of C-telopeptide and
      osteocalcin were 26%-66% higher as compared with 24 h mean values. The pattern of
      the circadian variation of C-telopeptide and osteocalcin was similar in female
      and male animals and was not significantly affected by restricted food intake.
      The sALP levels were only marginally affected by the circadian rhythm.
      Longitudinal variations, expressed as coefficient of variation (CV), for
      osteocalcin, C-telopeptide, and sALP concentrations were 17%, 14%, and 16%,
      respectively. In addition, the longitudinal variations were not significantly
      influenced by the time of blood collection in sALP and osteocalcin levels,
      whereas C-telopeptide levels showed significantly higher within-subject day-to
      day variation in morning samples, as compared with blood samples collected in the
      afternoon. The results highlight the importance of: (i) the timing of sample
      collection for appropriate interpretation of the bone marker data; and (ii) using
      the appropriate number of samples based on the variance obtained herein.

PMID- 11595620
TI  - Homologous growth hormone accelerates healing of segmental bone defects.
AB  - The effect of homologous recombinant porcine growth hormone (r-pGH) on secondary
      fracture healing was investigated in a diaphyseal defect of the tibia in Yucatan
      micropigs. A 1 cm defect of the tibia was created surgically and stabilized with
      an AO 3.5 mm DCP plate. The treatment group (12 animals) received 100 microg of r
      pGH per kilogram of body weight subcutaneously once per day, whereas the control
      pigs (12 animals) received 1 mL of sodium chloride as placebo. For evaluation of
      the GH-axis, serum levels of insulin-like growth factor-I (IGF-I) were sampled
      every fourth day. The animals were killed 6 weeks after surgery. Quantitative
      computed tomography (qCT) was performed to determine bone mineral density (BMD)
      and bone mineral content (BMC) of the defect zone. The torsional stiffness and
      the torsional failure load were measured by destructive torsional testing of the
      defect and contralateral tibiae. qCT measurements revealed a significant increase
      in the BMC of the defect zone in the treatment group compared with controls (GH
      BMC = 2833 +/- 679 mg, placebo BMC = 2215 +/- 636 mg; p < 0.05), whereas the BMD
      values were similar in both groups (GH BMD = 668 +/- 60 mg/mm(2), placebo BMD =
      629 +/- 52 mg/mm(2), p = 0.12). Torsional failure load was 70% higher and
      torsional stiffness 83% higher in the treatment group than in the control group
      (p < 0.05). The mean serum level of IGF-I in the treatment group increased to
      382% of the preoperative basal level and decreased to 69% in the control group,
      and this difference was highly significant (p < 0.001). Our data indicate that
      daily administration of recombinant GH leads to an increase of serum IGF-I levels
      and stimulates secondary fracture healing, resulting in increased mechanical
      strength and stiffness of the callus.

PMID- 11595621
TI  - Evaluation of the simple calculated osteoporosis risk estimation (SCORE) in a
      sample of white women from Belgium.
AB  - Identifying patients at risk of developing an osteoporosis-related fracture will
      continue to be a challenge. The "gold standard" for osteoporosis diagnosis is
      bone densitometry. However, economic issues or availability of the technology may
      prevent its use under a mass screening scenario. A risk assessment instrument,
      the "simple calculated osteoporosis risk estimation" (SCORE), has been reported
      to appropriately identify women likely to have low (t score < or = -2 SD) bone
      mineral density (BMD) and who should be referred for bone densitometry. The aim
      of our study is to evaluate the discriminatory performance of SCORE in a random
      sample of postmenopausal white women from Belgium. For this purpose, we gathered
      medical data on 4035 consecutive patients aged > or = 45 years, either consulting
      spontaneously or referred for a BMD measurement to an outpatient osteoporosis
      center located at the University of Liege, Belgium. BMD measurements, using dual
      energy X-ray absorptiometry (DXA) technology, were taken at the hip (total and
      neck) and lumbar spine (L2-4). At the recommended cutoff point of 6, SCORE had a
      sensitivity of 91.5% to detect low BMD at any of the measured sites, a
      specificity of 26.5%, a positive predictive value of 52.8%, and a negative
      predictive value of 77.7%. According to SCORE, 18% of the patients would not be
      recommended for densitometry. Among these, 10.9% were misclassified as they had
      osteoporosis (t score < or = -2.5 SD) at one or more of the sites investigated.
      The negative predictive errors of SCORE, when failing to detect osteoporosis,
      were only 1% for the total hip, 3.2% for the femoral neck, and 8.8% for the
      lumbar spine. We conclude that, notwithstanding the high values of sensitivity,
      SCORE specificity is too low to be useful as a diagnostic tool for screening
      patients at high risk to later develop osteoporosis. Nevertheless, from a
      resource allocation perspective, this instrument can be used with relative
      confidence to exclude patients who do not need a BMD measurement, and would
      therefore provide an opportunity to realize substantial cost savings in
      comparison to a mass screening strategy.

PMID- 11595622
TI  - Association between endogenous hormones and sex hormone-binding globulin and bone
      turnover in older women: study of osteoporotic fractures.
AB  - Estrogen therapy decreases bone remodeling, but the association between
      endogenous estradiol (E2), estrone (E1), testosterone (T), and bone turnover in
      older women is not clear. To test the association of serum E2, E1, free T, and
      sex hormone-binding globulin (SHBG) with bone turnover, we analyzed cross
      sectional relationships among E2, E1, T, SHBG, and biochemical markers of bone
      turnover serum osteocalcin [OC], serum bone-specific alkaline phosphatase [bAP],
      and serum breakdown products of C telopeptide of type I collagen [CTx] in 704
      women enrolled in the Study of Osteoporotic Fractures. Women with lower estradiol
      levels tended to have higher levels of bone turnover, but the association was
      weak (R(2) = 0.01 for the association E2-OC, p = 0.03; and R(2) = 0.024 for E2
      CTx, p = 0.001). Relationships between SHBG and turnover were also weak (R(2) for
      the association SHBG-OC was 0.07, p < 0.001, and 0.03 for SHBG-sCTx, p = 0.03),
      or not significant (R(2) < 0.01 for the association SHBG-bAP). Associations of E1
      and T with these markers were of the same magnitude. These results were not
      modified after adjustment for age, weight, and smoking status. We conclude that
      older women with low endogenous hormones have somewhat higher bone turnover, but
      these associations are weak. Bone turnover is determined mainly by factors other
      than endogenous concentrations of sex hormones.

PMID- 11595623
TI  - Muscle cross-sectional area is associated with specific site of bone in
      prepubertal girls: a quantitative magnetic resonance imaging study.
AB  - It is well established that forces applied to bone are the result of muscle
      contraction. However, data regarding the contribution of muscle cross-sectional
      area (because muscle area is proportional to muscle strength) to cortical bone
      area before puberty are controversial. We tested the hypothesis that muscle cross
      sectional area is associated with total cortical bone area, and whether there is
      a region-specific relationship between these parameters in prepubertal and early
      pubertal girls. Seventeen healthy (9-11 years, Tanner stages I-II) white girls
      participated in the study. We measured bone loading characteristics (maximal
      ground reaction forces; GRFs) for a drop jump (50 cm) and side-to-side jump (over
      a 20-cm-high fence) on a multicomponent force platform. Muscle cross-sectional
      area and bone cortical area (square centimeters) of the proximal third of the
      left and right lower leg was measured with a 1.5 T magnetic resonance system
      using a quadrature head coil. The sequence was T(1) weighted, with spin-echo in
      transverse (tibial) planes and 3 mm sections with no gap (ten slices). The tibial
      cross-sectional areas were subdivided into three anatomical sectors (SI-SIII),
      with the tibial centroid as origin. SI extended from the medial tibial border to
      the most anterior edge, SII extended from the anterior edge laterally to the
      interosseous border, and SIII extended posteromedially from the interosseous
      border to the medial tibial border. The nonparametric bone and muscle volume
      correlations demonstrated that the total muscle cross-sectional area correlated
      significantly with the total cortical area in both legs (left leg: r(s) = 0.59, p
      = 0.020; right leg: r(s) = 0.57, p = 0.016). Significant correlations were also
      found between left and right muscle area and cortical area in SII (r(s) = 0.68, p
      = 0.003, 0.67, and 0.003, respectively). There was no significant association
      between the muscle area and cortical area in SI or SIII. In addition, there was a
      significant correlation between GRFs of the side-to-side jump and total cortical
      area (left leg: r = 0.75, p < 0.01; right leg: r = 0.78, p < 0.01). Thus, we
      found that muscle area was most highly associated with bone cortical area in SII,
      the anterolateral sector of the tibia, which emphasizes the specific interplay of
      muscles and bone in the lower limb. This relationship was present in a regional,
      site-specific fashion.

PMID- 11595624
TI  - A case of neuroendocrine oncogenic osteomalacia associated with a PHEX and
      fibroblast growth factor-23 expressing sinusidal malignant schwannoma.
AB  - Oncogenic osteomalacia is a rare paraneoplastic syndrome that is characterized
      biochemically by hypophosphatemia and low plasma 1,25-dihydroxyvitamin D3, and
      clinically by osteomalacia, pseudofractures, bone pain, fatigue, and muscle
      weakness. We present a patient with a malignant schwannoma as the underlying
      cause of this disorder. A permanent cell line (HMS-97) derived from this tumor
      showed evidence of neuroendocrine differentiation by immunohistochemistry and of
      neurosecretory activity by electron microscopy. The cell line did express PHEX
      (phosphate-regulating gene with homologies to endopeptidases located on the X
      chromosome) and FGF-23 (fibroblast growth factor-23) transcripts on northern
      hybridization; however, none of the known mutations from the related mendelian
      disorders of X-linked hypophosphatemic rickets or autosomal-dominant
      hypophosphatemic rickets could be detected. Tumor cell (HMS-97)-derived
      conditioned medium did not inhibit phosphate transport in a standard opossum
      kidney cell assay and in animal experiments. The medium also showed no PTH1- or
      PTH2-receptor-stimulating bioactivity. HMS-97 cells might be useful for further
      studies that aim to determine the genetic mechanism that leads to the observed
      PHEX and FGF-23 expression, both of which might have a direct role in the
      pathogenesis of oncogenic osteomalacia. In addition, these cells might be a
      useful tool for the investigation of neuroendocrine Schwann cell function and
      autoimmune peripheral nerve disease.

PMID- 11595625
TI  - Escherichia coli cytotoxic necrotizing factors and Bordetella dermonecrotic
      toxin: the dermonecrosis-inducing toxins activating Rho small GTPases.
AB  - Escherichia coli cytotoxic necrotizing factors (CNFs) and Bordetella
      dermonecrotic toxin (DNT) have been recently found to comprise a novel family of
      dermonecrosis-inducing toxins which activate the small GTPases of the Rho family.
      They are single chain polypeptides consisting of an N-terminal domain responsible
      for binding to target cells and a C-terminal catalytic domain. CNFs (CNF1 and 2)
      and DNT share in the catalytic domain about 30% identical residues and a
      consensus sequence where the catalytically active center Cys resides. Both toxins
      deamidate Rho and other members of the Rho family, Rac and Cdc42, at Gln in the
      switch II region, which plays an important role in their GTPase activity. DNT, in
      addition, catalyzes a cross-link of the Gln of the GTPases with ubiquitous
      polyamines such as putrescine, spermidine, and spermine. The deamidation and the
      polyamination result in abrogation of the GTPase activity, and in addition, the
      polyamination endows Rho with the ability to interact with a downstream effector,
      ROCK, in a GTP-independent manner. These effects render the GTPases
      constitutively active, which underlies the toxicities of CNFs and DNT.

PMID- 11595626
TI  - Shiga toxins.
AB  - Shiga toxin and Shiga-like toxins belong to the group of protein toxins which
      have a moiety that binds to the cell surface and another enzymatically active
      moiety that after entry into the cytosol inhibits protein synthesis
      enzymatically. The toxins can also cause apoptosis by mechanisms that may be
      different from the effect on the protein synthesis machinery. Shigella
      dysenteriae, some strains of Escherichia coli as well as other bacteria can
      secrete such toxins which cause serious complications during infections. An
      increasing knowledge about the toxins and their interactions with cells is
      important both for treatment of disease, and for elucidation of pathways of
      intracellular transport.

PMID- 11595627
TI  - Not as simple as just punching a hole.
AB  - Like a variety of other pathogenic bacteria, Aeromonas hydrophila secretes a pore
      forming toxin that contribute to its virulence. The last decade has not only
      increased our knowledge about the structure of this toxin, called aerolysin, but
      has also shed light on how it interacts with its target cell and how the cell
      reacts to this stress. Whereas pore-forming toxins are generally thought to lead
      to brutal death by osmotic lysis of the cell, based on what is observed for
      erythrocytes, recent studies have started to reveal far more complicated pathways
      leading to death of nucleated mammalian cells.

PMID- 11595628
TI  - The Rho-ADP-ribosylating C3 exoenzyme from Clostridium botulinum and related C3
      like transferases.

PMID- 11595629
TI  - Mode of action of beta-barrel pore-forming toxins of the staphylococcal alpha
      hemolysin family.
AB  - Staphylococcal alpha-hemolysin is the prototype of a family of bacterial
      exotoxins with membrane-damaging function, which share sequence and structure
      homology. These toxins are secreted in a soluble form which finally converts into
      a transmembrane pore by assembling an oligomeric beta-barrel, with hydrophobic
      residues facing the lipids and hydrophilic residues facing the lumen of the
      channel. Besides alpha-hemolysin the family includes other single chain toxins
      forming homo-oligomers, e.g. beta-toxin of Clostridium perfringens, hemolysin II
      and cytotoxin K of Bacillus cereus, but also the staphylococcal bi-component
      toxins, like gamma-hemolysins and leucocidins, which are only active as the
      combination of two similar proteins which form hetero-oligomers. The molecular
      basis of membrane insertion has become clearer after the determination of the
      crystal structure of both the oligomeric pore and the soluble monomer. Studies on
      this family of beta-barrel pore-forming toxins are important for many aspects:
      (i) they are involved in serious pathologies of humans and farmed animals, (ii)
      they are a good model system to investigate protein-membrane interaction and
      (iii) they are the basic elements for the construction of nanopores with
      biotechnological applications in various fields.

PMID- 11595630
TI  - The cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli.
AB  - The cytotoxic necrotizing factor 1, from uropathogenic Escherichia coli, is the
      paradigm of Rho-GTPases-activating bacterial toxins. CNF1 is a MW 108kDa A-B
      protein toxin divided into three domains which are implicated in the three steps
      of the intoxication process. The N-terminal domain contains the cell receptor
      function and binds with high affinity to a cell receptor not yet identified.
      Binding of the toxin is followed by its internalization by endocytosis and its
      transport into late endosomes. The middle toxin domain contains two hydophobic
      helices which allow translocation of the toxin across the membrane upon
      acidification in late endosomes. Finally the carboxy-terminal domain of CNF1 is
      an enzyme which deamidates Rho-GTP-binding proteins (Rho, Rac and Cdc42)
      glutamine 63 (for Rho) or glutamine 61 (for Rac and Cdc42). Deamidation of
      glutamine 63/61 blocks the intrinsic or the GTPase activating protein (GAP)
      induced hydrolysis of GTP leading to the permanent activation of the GTPase.
      Activation of Rho GTPases by CNF1 induces a profound reorganization of the cell
      actin cytoskeleton. By its properties on Rho GTPases CNF1 is to date an
      invaluable tool for cell biology studies.

PMID- 11595631
TI  - The family of thiol-activated, cholesterol-binding cytolysins.
AB  - Several species of both pathogenic and non-pathogenic grampositive bacteria
      within the genera Streptococcus, Clostridium and Bacillus secrete cytolytic
      proteins that belong to a single, highly homologous family. The most widely known
      members of this family are streptolysin O, listeriolysin, perfringolysin, and
      pneumolysin. These toxins specifically require membrane cholesterol but,
      apparently, do not depend on any other specific cell surface receptor, so that
      they are able to lyse the cytoplasmic membranes of virtually any animal cell.
      Upon binding as monomers, they oligomerize to form large pores with up to 30 nm
      internal diameter. These are the largest pores known, permitting permeation not
      only of ions and small metabolites but also of macromolecules. The latter
      property renders these toxins useful tools in cell biology. While several of
      these cytolysins have been shown to be determinants of bacterial pathogenicity,
      their biological roles may vary, as do the lifestyles of the bacteria secreting
      them. A unique function is surely fulfilled by listeriolysin O, which helps the
      intracellular pathogen Listeria monocytogenes escape from phagolysosomes and then
      spread to adjacent host cells.

PMID- 11595632
TI  - Superantigen bacterial toxins: state of the art.
AB  - Superantigens (SAgs) are viral and bacterial proteins exhibiting a highly potent
      polyclonal lymphocyte-proliferating activity for CD4(+), CD8(+) and sometimes
      gammadelta(+) T cells of human and (or) various animal species. Unlike
      conventional antigens, SAgs bind as unprocessed proteins to invariant regions of
      major histocompatibility complex (MHC) class II molecules on the surface of
      antigen-presenting cells (APCs) and to particular motifs of the variable region
      of the beta chain (Vbeta) of T-cell receptor (TcR) outside the antigen-binding
      groove. As a consequence, SAgs stimulate at nano-to picogram concentrations up to
      10 to 30% of host T-cell repertoire while only one in 10(5)-10(6) T cells (0.01
      0.0001%) are activated upon conventional antigenic peptide binding to TcR. SAg
      activation of an unusually high percentage of T lymphocytes initiates massive
      release of pro-inflammatory and other cytokines which play a pivotal role in the
      pathogenesis of the diseases provoked by SAg-producing microorganisms. We briefly
      describe in this review the molecular and biological properties of the bacterial
      superantigen toxins and mitogens identified in the past decade.

PMID- 11595633
TI  - Clostridium botulinum and its neurotoxins: a metabolic and cellular perspective.
AB  - Clostridium botulinum comprises a diverse assemblage of clostridia that have the
      common property of producing a distinctive protein neurotoxin (BoNT) of similar
      pharmacological activity and extraordinary potency. BoNTs are produced in culture
      as molecular complexes consisting of BoNT, hemagglutinin (HA) and associated
      subcomponent proteins, nontoxic nonhemagglutinin (NTNH), and RNA. The genes
      encoding the protein components reside as a cluster on the chromosome, on
      bacteriophages, or on plasmids depending on the C. botulinum serotype. A gene
      BotR coding for a regulatory protein has been detected in toxin gene clusters
      from certain strains, as well as ORFs coding for uncharacterized components. The
      gene encoding TeNT is located on a large plasmid, and expression of the
      structural gene is controlled by the regulatory gene, TetR, located immediately
      upstream of the TeNT structural gene. TeNT is not known to be assembled into a
      protein/nucleic acid complex in culture. Cellular synthesis of BoNT and TeNT have
      been demonstrated to be positively regulated by the homologous proteins, BotR/A
      and TetR. Evidence suggests that negative regulatory factors and general control
      cascades such as those involved in nitrogen regulation and carbon catabolite
      repression also regulate synthesis of BoNTs. Neurotoxigenic clostridia have
      attracted considerable attention from scientists and clinicians during the past
      decade, and many excellent reviews are available on various aspects of these
      organisms and their neurotoxins. However, certain areas have not been well
      studied, including metabolic regulation of toxin formation and genetic tools to
      study neurotoxigenic clostridia. These topics are the focus of this review.

PMID- 11595634
TI  - Ricin.
AB  - The plant toxin ricin consists of two disulfide-linked polypeptides with
      different functions. The A-chain enters the cytosol and inactivates the ribosomes
      enzymatically, whereas the B-chain has lectin properties and binds to
      carbohydrates at the cell surface. This binding is a requirement for
      translocation of the A-chain to the cytosol. The bound toxin is endocytosed and
      transported retrograde through the Golgi apparatus to the endoplasmic reticulum
      where it appears to be translocated to the cytosol by the sec61p complex.

PMID- 11595635
TI  - The cytolethal distending toxins induce DNA damage and cell cycle arrest.
AB  - The cytolethal distending toxins (CDTs) are a newly discovered family of
      bacterial protein toxins with the unique ability to interfere with the cell
      cycle, causing irreversible cell cycle arrest and consequently death of the
      target cells. CDTs are encoded by three linked genes (cdtA, cdtB and cdtC) and
      are produced by a variety of Gram negative bacteria. The mechanism of action of
      this toxin family only now begins to be elucidated. CDTs are internalized by
      endocytosis and require an intact Golgi complex to exert their cytotoxic
      activity. The CdtB component was shown to have functional homology with the
      mammalian deoxyribonuclease I (DNase I) and the induction of cell cycle arrest in
      mammalian cells mimicked that induced by DNA damaging agents, suggesting that DNA
      is the cellular target. Still there are many issues that need to be clarified,
      such as identification of the function(s) of CdtA and CdtC, characterization of
      the receptor(s), understanding of the final steps of the internalization pathway
      and localization of the active component. This review focuses mainly on the
      effect of CDTs on mammalian cells, highlighting the questions that remain to be
      answered regarding their molecular mode of action.

PMID- 11595636
TI  - The toxins of Bacteroides fragilis.
AB  - Bacteroides fragilis are both key commensals and important human pathogens.
      Particular strains of B. fragilis, termed enterotoxigenic B. fragilis (ETBF), are
      recently identified enteric pathogens of children and adults. These strains are
      distinguished by secretion of a 20kDa metalloprotease toxin (B. fragilis toxin or
      BFT), the first recognized and only established toxin to date for B. fragilis.
      Three isotypes of BFT are encoded by distinct bft loci contained within a 6kb
      chromosomal region unique to ETBF strains termed the B. fragilis pathogenicity
      island (BfPAI). Experimental studies have suggested that the cellular target for
      BFT is E-cadherin, the primary protein of the zonula adherens. It is postulated
      that BFT cleavage of E-cadherin is critical in precipitating the intracellular
      events culminating in the two established activities for BFT; namely, stimulation
      of secretion in ligated intestinal segments in several animal species and
      alteration of cellular morphology only in epithelial cells that retain the
      ability to polarize and form a tight junctional complex. Future studies will be
      directed to characterizing in greater detail both the molecular genetics of the
      BFT toxin and the precise steps in its cellular mechanism of action.

PMID- 11595637
TI  - Toxins of Bacillus anthracis.
AB  - Bacillus anthracis, a gram positive bacterium, is the causative agent of anthrax.
      This organism is capsulogen and toxinogenic. It secretes two toxins which are
      composed of three proteins: the protective antigen (PA), the lethal factor (LF)
      and the edema factor (EF). The lethal toxin (PA+LF) provokes a subit death in
      animals, the edema toxin (PA+EF) induces edema. The edema and the lethal factors
      are internalised into the eukaryotic target cells via the protective antigen. EF
      and LF exert a calmoduline dependent adenylate cyclase and a metalloprotease
      activity respectively. Progress in the structure-function relationship of these
      three proteins, their regulation mechanisms and their roles in pathogenesis and
      immunoprotection will be exposed.

PMID- 11595638
TI  - In search of the Helicobacter pylori VacA mechanism of action.
AB  - Helicobacter pylori secretes an approximately 88 kDa VacA toxin that is
      considered to be an important virulence factor in the pathogenesis of peptic
      ulcer disease. Over the past decade, research on the molecular mechanisms and
      biological functions of VacA has generated a complex and often puzzling scenario.
      VacA is secreted into the extracellular space and also is partially retained on
      the bacterial cell surface, exists in monomeric and oligomeric forms, and binds
      to multiple eukaryotic cell-surface receptors. The cellular effects induced by
      VacA include vacuolation, alteration of endo-lysosomal function, pore formation
      in the plasma membrane, apoptosis, and epithelial monolayer permeabilisation.
      VacA has been reported to target several different cell components, including
      endocytic vesicles, mitochondria, the cytoskeleton, and epithelial cell-cell
      junctions. It remains unclear whether VacA should be classified as an A/B type
      toxin, a channel-forming toxin, or both. This review is intended to summarise our
      current knowledge about VacA, and to orient the reader to this fascinating and
      challenging research area.

PMID- 11595639
TI  - Clostridial hydrolytic enzymes degrading extracellular components.
AB  - Bacteria belonging to the genus Clostridium, both glycolytic and proteolytic, and
      both pathogenic and non-pathogenic, produce a battery of hydrolytic enzymes to
      obtain nutrients from various biopolymers. The clostridial hydrolytic enzymes are
      diverse, and are used or are potentially useful for fundamental and applied
      research purposes. Among them, enzymes degrading the major components in the
      extracellular matrix or on the cell surface in vertebrates are herein reviewed
      with special emphasis on recent knowledge gained through molecular biology of
      clostridial collagenases, sialidases and hyaluronidases. This paper also reviews
      some literature on the biotechnological approach to the designing of new
      molecular tools and drug delivery systems involving clostridial hydrolytic
      enzymes.

PMID- 11595640
TI  - The complex interactions between Clostridium perfringens enterotoxin and
      epithelial tight junctions.
AB  - Clostridium perfringens enterotoxin (CPE) is responsible for the diarrheal
      symptoms of C. perfringens type A food poisoning and antibiotic-associated
      diarrhea. The CPE protein consists of a single 35 kDa polypeptide with a C
      terminal receptor-binding region and an N-terminal toxicity domain. Under
      appropriate conditions, CPE can interact with structural components of the
      epithelial tight junctions, including certain claudins and occludin. Those
      interactions can affect tight junction structure and function, thereby altering
      paracellular permeability and (possibly) contributing to CPE-induced diarrhea.
      However, the tight junction effects of CPE require cellular damage as a
      prerequisite. CPE induces cellular damage via its cytotoxic activity, which
      results from plasma membrane permeability alterations caused by formation of a
      approximately 155 kDa CPE-containing complex that may correspond to a pore. Thus,
      CPE appears to be a bifunctional toxin that first induces plasma membrane
      permeability alterations; using the resultant cell damage, CPE then gains access
      to tight junction proteins and affects tight junction structure and function.

PMID- 11595641
TI  - Understanding the mode of action of diphtheria toxin: a perspective on progress
      during the 20th century.
AB  - Diphtheria toxin is one of the most extensively studied and well understood
      bacterial toxins. Ever since its discovery in the late 1800's this toxin has
      occupied a central focus in the field of toxinology. In this review, I present a
      chronology of major discoveries that led to our current understanding of the
      structure and activity of diphtheria toxin.

PMID- 11595642
TI  - Ethics, revisited.

PMID- 11595643
TI  - Evaluation of dietary assessment instruments against doubly labeled water, a
      biomarker of habitual energy intake.
AB  - Epidemiological studies of diet and disease rely on the accurate determination of
      dietary intake and subsequent estimates of nutrient exposure. Although
      methodically developed and tested, the instruments most often used to collect
      self-reported intake data are subject to error. It had been assumed that this
      error was only random in nature; however, an increasing body of literature
      suggests that systematic error in the reporting of true dietary intake exists as
      well. Here, we review studies in which dietary intake by self report was
      determined while energy expenditure was simultaneously measured using the doubly
      labeled water (DLW) method. In seeking to establish the relative accuracy of each
      instrument to capture true habitual energy intake, we conclude that none of the
      self-reported intake instruments demonstrates greater accuracy against DLW.
      Instead, it is evident that the physical and psychological characteristics of
      study participants play a significant role in the underreporting bias observed in
      these studies. Further research is needed to identify underreporters and to
      determine how to account for this bias in studies of diet and health.

PMID- 11595644
TI  - Cubilin and megalin expression and their interaction in the rat intestine: effect
      of thyroidectomy.
AB  - Cubilin is a 460-kDa multipurpose, multidomain receptor that contains an NH(2)
      terminal 110-residue segment followed by 8 epidermal growth factor (EGF)-like
      repeats and a contiguous stretch (representing nearly 88% of its mass) of 27 CUB
      (initially found in complement components C1r/C1s, Uegf, and bone morphogenic
      protein-1) domains. Cubilin binds to intrinsic factor (IF)-cobalamin (cbl,
      vitamin B(12)) complex and promotes the ileal transport of cbl. The 460-kDa form
      of cubilin is the predominant form present in the apical brush-border membranes
      of rat intestine, kidney, and yolk sac, but a 230-kDa form of cubilin is also
      noted in the intestinal membranes. In thyroidectomized (TDX) rats, levels of
      intestinal brush-border IF-[(57)Co]-labeled cbl binding, 460-kDa cubilin protein
      levels and tissue (kidney) accumulation of cbl were reduced by approximately 70%.
      Immunoblot analysis using cubilin antiserum of intestinal total membranes from
      TDX rats revealed cubilin fragments with molecular masses of 200 and 300 kDa.
      Both of these bands, along with the 230-kDa band detected in the total membranes
      of control rats and unlike the 460-kDa form, failed to react with antiserum to
      EGF. Mucosal membrane cubilin associated with megalin was reduced from
      approximately 12% in control to approximately 4% in TDX rats, and this decreased
      association was not due to altered megalin levels. Thyroxine treatment of TDX
      rats resulted in reversal of all of these effects, including an increase to
      nearly 24% of cubilin associated with megalin. In vitro, megalin binding to
      cubilin occurred with the NH(2)-terminal region that contained the EGF-like
      repeats and CUB domains 1 and 2 but not with a downstream region that contained
      CUB domains 2-10. These studies indicate that thyroxine deficiency in rats
      results in decreased uptake and tissue accumulation of cbl caused mainly by
      destabilization and deficit of cubilin in the intestinal brush border.

PMID- 11595645
TI  - Developmental changes in the feeding-induced activation of the insulin-signaling
      pathway in neonatal pigs.
AB  - In neonatal animals, feeding stimulates skeletal muscle protein synthesis, a
      response that declines with development. Both the magnitude of the feeding
      response and its developmental decline can be reproduced by insulin infusion,
      suggesting that an altered responsiveness to insulin is a primary determinant of
      the developmental decline in the stimulation of protein synthesis by feeding. In
      this study, 7- and 26-day-old pigs were either fasted overnight or fed porcine
      milk after an overnight fast. We examined the abundance and degree of tyrosine
      phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS
      1), and IRS-2 in skeletal muscle and, for comparison, liver. We also evaluated
      the association of IRS-1 and IRS-2 with phosphatidylinositol 3-kinase (PI 3
      kinase). The abundance of IR protein in muscle was twofold higher at 7 than at 26
      days, but IRS-1 and IRS-2 abundances were similar in muscle of 7- and 26-day-old
      pigs. The feeding-induced phosphorylations were greater at 7 than at 26 days of
      age for IR (28- vs. 13-fold), IRS-1 (14- vs. 8-fold), and IRS-2 (21- vs. 12-fold)
      in muscle. The associations of IRS-1 and IRS-2 with PI 3-kinase were also
      increased by refeeding to a greater extent at 7 than at 26 days (9- vs. 5-fold
      and 6- vs. 4-fold, respectively). In liver, the abundance of IR, IRS-1, and IRS-2
      was similar at 7 and 26 days of age. Feeding increased the activation of IR, IRS
      1, IRS-2, and PI 3-kinase in liver only twofold, and these responses were
      unaffected by age. Thus our findings demonstrate that the feeding-induced
      activation of IR, IRS-1, IRS-2, and PI 3-kinase in skeletal muscle decreases with
      development. Further study is needed to ascertain whether the developmental
      decline in the feeding-induced activation of early insulin-signaling components
      contributes to the developmental decline in translation initiation in skeletal
      muscle.

PMID- 11595646
TI  - Gut expression and regulation of FAT/CD36: possible role in fatty acid transport
      in rat enterocytes.
AB  - Fatty acid translocase (FAT)/CD36 is one of several putative plasma membrane long
      chain fatty acid (LCFA) transport proteins; however, its role in intestinal
      absorption of LCFA is unknown. We hypothesized that FAT/CD36 would be
      differentially expressed along the longitudinal axis of the gut and during
      intestinal development, suggesting specificity of function. We found that
      intestinal mucosal FAT/CD36 mRNA levels varied by anatomic location along the
      longitudinal gut axis: stomach 45 +/- 7, duodenum 173 +/- 29, jejunum 238 +/- 17,
      ileum 117 +/- 14, and colon 9 +/- 1% (means +/- SE with 18S mRNA as control).
      FAT/CD36 protein levels were also higher in proximal compared with distal
      intestinal mucosa. Mucosal FAT/CD36 mRNA was also regulated during intestinal
      maturation, with a fourfold increase from neonatal to adult animals. In addition,
      FAT/CD36 mRNA levels and enterocyte LCFA uptake were rapidly downregulated by
      intraduodenal oleate infusion. These findings suggest that FAT/CD36 plays a role
      in the uptake of LCFA by small intestinal enterocytes. This may have important
      implications in understanding fatty acid absorption in human physiological and
      pathophysiological conditions.

PMID- 11595647
TI  - Intermittent high glucose enhances apoptosis in human umbilical vein endothelial
      cells in culture.
AB  - To explore the effect of fluctuating glucose on endothelial cells, human
      umbilical vein endothelial cells were incubated for 14 days in media containing
      different glucose concentrations: 5 mmol/l, 20 mmol/l, or a daily alternating 5
      or 20 mmol/l glucose. Apoptosis was studied by different methods: viability
      assay, cell cycle analysis, DNA fragmentation, and morphological analysis.
      Furthermore, the levels of Bcl-2 and Bax, well known proteins involved in
      apoptosis, were evaluated. Stable high glucose induced apoptosis in human
      umbilical vein endothelial cells, a phenomenon accompanied by a significant
      decrease of Bcl-2 and a simultaneous increase of Bax expression. However,
      apoptosis was enhanced in human umbilical vein endothelial cells exposed to
      intermittent, rather than constant, high glucose concentration. In this
      condition, Bcl-2 was not detectable, whereas Bax expression was significantly
      enhanced. These findings suggest that variability in glycemic control could be
      more deleterious to endothelial cells than a constant high concentration of
      glucose.

PMID- 11595648
TI  - CaMKIV/Gr is dispensable for spermatogenesis and CREM-regulated transcription in
      male germ cells.
AB  - The calcium/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is
      expressed in male germ cells and spermatids and has been implicated in
      controlling the differentiation of germ cells into mature spermatozoa. The
      function of CaMKIV/Gr in spermatogenesis was investigated using CaMKIV/Gr
      deficient mice generated by targeted gene disruption. CaMKIV/Gr-deficient males
      exhibited normal spermatogenesis, and their fertility was similar to that of wild
      type littermates. Notwithstanding the function of CaMKIV/Gr as an activator of
      cAMP response element (CRE)-dependent transcription, mRNA levels of several
      testis-specific CRE modulator (CREM)-regulated genes were unaltered. These
      results indicate that CaMKIV/Gr is not essential for spermatogenesis or for CRE
      regulated gene transcription in the testis.

PMID- 11595649
TI  - Glucose and forskolin regulate IAPP gene expression through different signal
      transduction pathways.
AB  - Molecular mechanisms for the regulation of islet amyloid polypeptide (IAPP) gene
      expression remain unclear. In the present study, we investigated the effects of
      glucose and forskolin on IAPP gene regulation in the INS-1 islet beta-cell line.
      Both glucose and forskolin increased the level of expression of this gene, as
      measured by Northern blot analysis, and increased IAPP gene transcription in a
      time- and concentration-dependent manner, as demonstrated in a reporter gene
      assay. Although inhibition of protein kinase A activity with H-89 eliminated the
      effect of forskolin on this gene, the glucose effect was unaffected. This
      supported the predominant use of a protein kinase A-independent signaling pathway
      for glucose regulation of the IAPP gene. Electrophoretic mobility shift assay
      further indicated that glucose and forskolin regulated expression of this gene by
      targeting different elements of the promoter. Mutation of the cAMP regulatory
      element flanking the IAPP coding region resulted in the loss of most of the
      forskolin-stimulated IAPP gene promoter activity, whereas glucose-enhanced IAPP
      gene transcription was unaffected. These results demonstrate parallel and
      distinct regulatory pathways involved in glucose- and forskolin-induced IAPP gene
      expression in this model beta-cell system.

PMID- 11595650
TI  - A nonlabeled method to evaluate cortisol production rate by modeling plasma CBG
      free cortisol disposition.
AB  - This study aimed to develop a nonlabeled method for the measurement of cortisol
      production rate to evaluate adrenal function. The cortisol production rate
      determination requires that of cortisol clearance, which is not a parameter but a
      variable resulting from the saturable binding of cortisol to corticosteroid
      binding globulin (CBG). Our method is based on evaluation of the plasma clearance
      of the CBG-free cortisol fraction. This parameter was evaluated from a
      pharmacokinetic model of total plasma cortisol disposition that takes into
      account specific binding of the corticoid to CBG in the plasma. We have shown
      that the CBG-free cortisol kinetics and CBG-binding parameters thus evaluated are
      not statistically different from those obtained by the radioisotopic method and
      equilibrium dialysis, suggesting that the plasma CBG-free cortisol clearance is
      independent of the total plasma cortisol concentrations and represents the actual
      parameter of cortisol elimination. We validated this modeling approach by using
      it to calculate the in vivo entry rate of cortisol mimicked by the perfusion of
      cortisol at a known rate.

PMID- 11595651
TI  - Reduced body fat and increased hepatic lipid synthesis in mice bearing
      interleukin-6-secreting tumor.
AB  - Chronic secretion of interleukin-6 (IL-6) in mice causes metabolic alteration in
      the liver, leading to increased synthesis of hepatic cholesterol and fatty acids
      (FA). Mice were injected with allogeneic tumor cells transduced with the murine
      IL-6 gene. During the 3 wk after tumor inoculation, elevated serum IL-6 levels
      were associated with increased spleen and liver weight. Histological examination
      of sections from the liver showed increased hepatocyte proliferation, resulting
      in liver enlargement. Body composition analysis revealed that IL-6 caused a
      significant loss in fat tissue without affecting lean body mass and water
      content. Hepatic de novo synthesis of FA and cholesterol, as measured by (3)H(2)O
      incorporation, was three to five times as high in mice secreting IL-6 (IL-6 mice)
      as in pair-fed mice bearing nonsecreting tumors. This increase in FA and
      cholesterol synthesis is sufficient to maintain hepatic triglyceride secretion at
      levels comparable with those of pair-fed mice bearing nonsecreting tumors and,
      presumably, is the main source of cholesterol and FA-phospholipids necessary for
      hepatocyte proliferation.

PMID- 11595652
TI  - Insulin and C-peptide secretion and kinetics in humans: direct and model-based
      measurements during OGTT.
AB  - To directly evaluate prehepatic secretion of pancreatic hormones during a 3-h
      oral glucose tolerance test (OGTT), we measured insulin and C-peptide in six
      healthy control, six obese, and six type 2 diabetic subjects in the femoral
      artery and hepatic vein by means of the hepatic catheterization technique.
      Hypersecretion in obesity was confirmed (309 +/- 66 nmol in obese vs. 117 +/- 22
      in control and 79 +/- 13 in diabetic subjects, P </= 0.01), whereas early phase
      secretion was impaired in diabetes. We also measured hepatic insulin extraction
      (higher in diabetic than in control subjects, P = 0.03) and insulin clearance.
      The measured data were also used to validate a previously proposed mathematical
      model, developed to quantify prehepatic secretion, hepatic insulin extraction,
      and insulin clearance during OGTT, when C-peptide and insulin concentrations are
      systemically measured. We found good correspondence between experimental data and
      model estimates for prehepatic insulin secretion (P > 0.3, r(2) = 0.93), whereas
      estimation of hepatic insulin extraction and insulin clearance needs further
      investigation for improvement.

PMID- 11595653
TI  - Effects of fasting on muscle mitochondrial energetics and fatty acid metabolism
      in Ucp3(-/-) and wild-type mice.
AB  - Uncoupling protein-3 (UCP3) is a mitochondrial carrier protein of as yet
      undefined physiological function. To elucidate characteristics of its function,
      we studied the effects of fasting on resting metabolic rate, respiratory
      quotient, muscle Ucp3 expression, and mitochondrial proton leak in wild-type and
      Ucp3(-/-) mice. Also analyzed were the fatty acid compositions of skeletal muscle
      mitochondria in fed and fasted Ucp3(-/-) and wild-type mice. In wild-type mice,
      fasting caused significant increases in Ucp3 (4-fold) and Ucp2 (2-fold) mRNA but
      did not significantly affect mitochondrial proton leak. State 4 oxygen
      consumption was not affected by fasting in either of the two groups. However,
      protonmotive force was consistently higher in mitochondria of Ucp3(-/-) animals
      (P = 0.03), and fasting further augmented protonmotive force in Ucp3(-/-) mice;
      there was no effect in wild-type mitochondria. Resting metabolic rates decreased
      with fasting in both groups. Ucp3(-/-) mice had higher respiratory quotients than
      wild-type mice in fed resting states, indicating impaired fatty acid oxidation.
      Altogether, results show that the fasting-induced increases in Ucp2 and Ucp3 do
      not correlate with increased mitochondrial proton leak but support a role for
      UCP3 in fatty acid metabolism.

PMID- 11595654
TI  - Triidothyronine and epinephrine rapidly modify myocardial substrate selection: a
      (13)C isotopomer analysis.
AB  - Triiodothyronine (T(3)) exerts direct action on myocardial oxygen consumption
      (MVO(2)), although its immediate effects on substrate metabolism have not been
      elucidated. The hypothesis, that T(3) regulates substrate selection and flux, was
      tested in isovolumic rat hearts under four conditions: control, T(3) (10 nM),
      epinephrine (Epi), and T(3) and Epi (TE). Hearts were perfused with [1,3
      (13)C]acetoacetic acid (AA, 0.17 mM), L-[3-(13)C]lactic acid (LAC, 1.2 mM), U
      (13)C-labeled long-chain free fatty acids (FFA, 0.35 mM), and unlabeled D-glucose
      (5.5 mM) for 30 min. Fractional acetyl-CoA contribution to the tricarboxylic acid
      cycle (Fc) per substrate was determined using (13)C NMR and isotopomer analysis.
      Oxidative fluxes were calculated using Fc, the respiratory quotient, and MVO(2).
      T(3) increased (P < 0.05) Fc(FFA), decreased Fc(LAC), and increased absolute FFA
      oxidation from 0.58 +/- 0.03 to 0.68 +/- 0.03 micromol. min(-1). g dry wt(-1) (P
      < 0.05). Epi decreased Fc(FFA) and Fc(AA), although FFA flux increased from 0.58
      +/- 0.03 to 0.75 +/- 0.09 micromol. min(-1). g dry wt(-1). T(3) moderated the
      change in Fc(FFA) induced by Epi. In summary, T(3) exerts direct action on
      substrate pathways and enhances FFA selection and oxidation, although the Epi
      effect dominates at a high work state.

PMID- 11595655
TI  - Estimation of gluconeogenesis in newborn infants.
AB  - The rate of glucose turnover (R(a)) and gluconeogenesis (GNG) via pyruvate were
      quantified in seven full-term healthy babies between 24 and 48 h after birth and
      in twelve low-birth-weight infants on days 3 and 4 by use of [(13)C(6)]glucose
      and (2)H(2)O. The preterm babies were receiving parenteral alimentation of either
      glucose or glucose plus amino acid with or without lipids. The contribution of
      GNG to glucose production was measured by the appearance of (2)H on C-6 of
      glucose. Glucose R(a) in full-term babies was 30 +/- 1.7 (SD) micromol. kg(-1).
      min(-1). GNG via pyruvate contributed approximately 31% to glucose R(a). In
      preterm babies, the contribution of GNG to endogenous glucose R(a) was variable
      (range 6-60%). The highest contribution was in infants receiving low rates of
      exogenous glucose infusion. In an additional group of infants of normal and
      diabetic mothers, lactate turnover and its incorporation into glucose were
      measured within 4-24 h of birth by use of [(13)C(3)]lactate tracer. The rate of
      lactate turnover was 38 micromol. kg(-1). min(-1), and lactate C, not corrected
      for loss of tracer in the tricarboxylic acid cycle, contributed approximately 18%
      to glucose C. Lactate and glucose kinetics were similar in infants that were
      small for their gestational age and in normal infants or infants of diabetic
      mothers. These data show that gluconeogenesis is evident soon after birth in the
      newborn infant and that, even after a brief fast (5 h), GNG via pyruvate makes a
      significant contribution to glucose production in healthy full-term infants.
      These data may have important implications for the nutritional support of the
      healthy and sick newborn infant.

PMID- 11595656
TI  - Sources of blood glycerol during fasting.
AB  - To determine the source(s) of blood and very low density lipoprotein (VLDL)
      triglyceride glycerol during fasting, four men ingested (2)H(2)O from 14 to 20 h
      into a 60-h fast to achieve ~0.5% body water enrichment. At 60 h of fasting,
      glycerol flux was measured using [2-(14)C]glycerol. Blood was taken for
      measurement of (2)H enrichment at carbon 6 of glucose and at carbon 3 of free
      glycerol and VLDL-triglyceride glycerol. (2)H enrichment of the 2 hydrogens bound
      to carbon 3 of VLDL-triglyceride glycerol was 105 +/- 2% of the (2)H enrichment
      of the 2 hydrogens bound to carbon 6 of glucose, indicating isotopic equilibrium
      between hepatic glyceraldehyde 3-P and glycerol 3-P. The (2)H enrichment of the 2
      hydrogens bound to carbon 3 of free glycerol was 17 +/- 3% of VLDL-triglyceride
      glycerol, indicating that a significant percentage of free glycerol in blood
      originated from the hydrolysis of circulating VLDL-triglyceride or a pool of
      glycerol with similar (2)H enrichment. Glycerol flux was 6.3 +/- 1.1 micromol.
      kg(-1). min(-1). Glycerol appearing from nonadipose tissue sources was then
      approximately 1.1 micromol. kg(-1). min(-1). Seven other subjects were fasted for
      12, 42, and 60 h. A small percentage of glycerol in the circulation after 12 h of
      fasting was enriched with (2)H. The enrichment of the 2 hydrogens bound to carbon
      3 of free glycerol in the longer periods of fasting was approximately 16% of the
      enrichment of the 2 hydrogens bound to carbon 6 of glucose. Therefore, as much as
      15-20% of systemic glycerol turnover during fasting is not from lipolysis of
      adipose tissue triglyceride.

PMID- 11595657
TI  - New equations for estimating body cell mass from bioimpedance parallel models in
      healthy older Germans.
AB  - The objectives of this study were to assess for elderly Germans the validity of
      existing equations for predicting body cell mass (BCM) and to develop from single
      and multifrequency bioimpedance (SFBIA, MFBIA) models new prediction equations.
      In a data-splitting approach, validation and cross-validation were performed in
      160 healthy elderly (60- to 90-yr) subjects. BCM was determined using a
      tetrapolar bioimpedance analyzer (800 microA; 4 fixed frequencies: 1, 5, 50, and
      100 kHz; electrodes placed to hand, wrist, ankle, and foot) and whole body (40)K
      counting as a reference method. New prediction equations were derived by multiple
      stepwise regression analysis. The Bland-Altman procedure was used for methods
      comparison. Relative to whole body counting, the manufacturer's equation
      overestimated BCM by 9% in men (P < 0.0001, paired t-test) and 4% in women (P =
      0.002). Compared with the manufacturer's equation, the newly derived equations (r
      = 0.92, RMSE = 6-9%) improved accuracy (pure error = 13 vs. 7-8%) and reduced
      bias and limits of agreement. SFBIA and MFBIA equations did not differ in
      precision or accuracy. We conclude that the newly derived equations improved BCM
      estimates in the elderly compared with existing equations. There was no advantage
      of MFBIA over SFBIA equations.

PMID- 11595658
TI  - N-glycosylation of CRF receptor type 1 is important for its ligand-specific
      interaction.
AB  - The corticotropin-releasing factor (CRF) receptor type 1 (CRFR1) contains five
      potential N-glycosylation sites: N38, N45, N78, N90, and N98. Cells expressing
      CRFR1 were treated with tunicamycin to block receptor glycosylation. The
      nonglycosylated receptor did not bind the radioligand and had a decreased cAMP
      stimulation potency in response to CRF. To determine which of the polysaccharide
      chain(s) is/are involved in ligand interaction, the polysaccharide chains were
      deleted using site-directed mutagenesis of the glycosylation consensus, N-X-S/T.
      Two sets of mutations were performed for each glycosylation site: N to Q and S/T
      to A, respectively. The single mutants Q38, Q45, Q78, Q90, Q98, A40, A47, A80,
      A92, and A100 and the double mutants A40/A47 and A80/A100 were well expressed,
      bound CRF, sauvagine (SVG), and urotensin-I (UTS-I) with a normal affinity, and
      increased cAMP accumulation with a high efficiency. In contrast, the combined
      mutations A80/A92/A100, A40/A80/A92/A100, and A40/A47/A80/A92/A100 had low levels
      of expression, did not bind the radioligand, and had a decreased cAMP
      stimulation. These data indicate the requirement for three or more polysaccharide
      chains for normal CRFR1 function.

PMID- 11595659
TI  - Mechanisms of insulin resistance in cystic fibrosis.
AB  - Cystic fibrosis (CF) is associated with a high incidence of diabetes. Studies
      evaluating causes of CF-related diabetes (CFRD) have consistently documented
      decreased insulin secretion. In patients with CFRD, insulin sensitivity has been
      documented to be decreased, but controversy exists in patients with normal or
      impaired glucose tolerance (IGT). We undertook this study 1) to reexplore insulin
      sensitivity in patients with IGT and 2) to evaluate potential mechanisms of
      insulin resistance in CF, including GLUT-4 translocation, elevation of serum
      cytokines, and free fatty acid (FFA) levels. We recruited nine CF subjects with
      impaired glucose tolerance (IGTCF) and nine age-, gender-, and body mass index
      matched control volunteers. Each underwent a hyperinsulinemic euglycemic clamp
      (200 mU. m(-2). min(-1)) to measure insulin sensitivity. A muscle biopsy was
      obtained at maximal insulin stimulation for measure of GLUT-4 translocation with
      sucrose gradients. An oral glucose tolerance test and National Institutes of
      Health (NIH) clinical status scores were measured in all volunteers. We also
      measured tumor necrosis factor (TNF)-alpha levels and FFA in all subjects.
      Additionally, we report the results of TNF-alpha and FFA in 32 CF patients
      previously studied by our group. Results were that glucose disposal rate (GDR)
      was significantly lower in the CFIGT subjects than in controls, indicative of
      impaired insulin action. GLUT-4 translocation was impaired in CF and correlated
      with GDR. TNF-alpha levels were higher in all CF subjects than in controls and
      correlated with GDR. There was no difference in FFA between CF and control
      subjects. Modified NIH clinical status scores were inversely correlated with GDR
      and TNF-alpha levels. We conclude that IGTCF patients have decreased peripheral
      insulin sensitivity. Mechanisms include elevation of TNF-alpha and impaired
      translocation of GLUT-4.

PMID- 11595660
TI  - Cardiac responses to insulin-induced hypoglycemia in nondiabetic and intensively
      treated type 1 diabetic patients.
AB  - Insulin-induced hypoglycemia occurs commonly in intensively treated patients with
      type 1 diabetes, but the cardiovascular consequences of hypoglycemia in these
      patients are not known. We studied left ventricular systolic [left ventricular
      ejection fraction (LVEF)] and diastolic [peak filling rate (PFR)] function by
      equilibrium radionuclide angiography during insulin infusion (12 pmol. kg(-1).
      min(-1)) under either hypoglycemic (approximately 2.8 mmol/l) or euglycemic
      (approximately 5 mmol/l) conditions in intensively treated patients with type 1
      diabetes and healthy nondiabetic subjects (n = 9 for each). During hypoglycemic
      hyperinsulinemia, there were significant increases in LVEF (DeltaLVEF = 11 +/-
      2%) and PFR [DeltaPFR = 0.88 +/- 0.18 end diastolic volume (EDV)/s] in diabetic
      subjects as well as in the nondiabetic group (DeltaLVEF = 13 +/- 2%; DeltaPFR =
      0.79 +/- 0.17 EDV/s). The increases in LVEF and PFR were comparable overall but
      occurred earlier in the nondiabetic group. A blunted increase in plasma
      catecholamine, cortisol, and glucagon concentrations occurred in response to
      hypoglycemia in the diabetic subjects. During euglycemic hyperinsulinemia, LVEF
      also increased in both the diabetic (DeltaLVEF = 7 +/- 1%) and nondiabetic
      (DeltaLVEF = 4 +/- 2%) groups, but PFR increased only in the diabetic group. In
      the comparison of the responses to hypoglycemic and euglycemic hyperinsulinemia,
      only the nondiabetic group had greater augmentation of LVEF, PFR, and cardiac
      output in the hypoglycemic study (P < 0.05 for each). Thus intensively treated
      type 1 diabetic patients demonstrate delayed augmentation of ventricular function
      during moderate insulin-induced hypoglycemia. Although diabetic subjects have a
      more pronounced cardiac response to hyperinsulinemia per se than nondiabetic
      subjects, their response to hypoglycemia is blunted.

PMID- 11595661
TI  - Human adipose tissue endothelial cells promote preadipocyte proliferation.
AB  - Adipogenesis is preceded by development of a microvascular network, and optimal
      functioning of adipose tissue as an energy store and endocrine organ is dependent
      on extensive vascularization. We have examined the role of endothelial cell
      derived factors that influence the proliferation of human preadipocytes.
      Microvascular endothelial cells and preadipocytes were isolated from human
      omental and subcutaneous adipose tissue biopsies by use of a developed procedure
      of collagenase digest, immunoselection, and differential trypsinization.
      Conditioned medium from microvascular endothelial cell cultures promoted the
      proliferation of preadipocytes (P = <0.001) and (to a lesser extent) other cell
      types. No depot-specific differences in mitogenic capacity of microvascular
      endothelial cell medium or of preadipocyte response were observed. These results
      indicate that adipose tissue endothelial cells secrete soluble adipogenic
      factor(s).

PMID- 11595662
TI  - Insulin fails to stimulate muscle protein synthesis in sepsis despite unimpaired
      signaling to 4E-BP1 and S6K1.
AB  - Induction of sepsis in rats causes an inhibition of protein synthesis in skeletal
      muscle that is resistant to the stimulatory actions of insulin. To gain a better
      understanding of the underlying reason for this lack of response, the present
      study was undertaken to investigate sepsis-induced alterations in insulin
      signaling to regulatory components of mRNA translation. Experiments were
      performed in perfused hindlimb preparations from rats 5 days after induction of a
      septic abscess. Sepsis resulted in a 50% reduction in protein synthesis in the
      gastrocnemius. Protein synthesis in muscles from septic rats, but not controls,
      was unresponsive to stimulation by insulin. The insulin-induced
      hyperphosphorylation response of the translation repressor protein 4E-binding
      protein 1 (4E-BP1) and of the 70-kDa S6 kinase (S6K1) (1), two targets of insulin
      action on mRNA translation, was unimpaired in gastrocnemius of septic rats.
      Hyperphosphorylation of 4E-BP1 in response to insulin resulted in its
      dissociation from the inactive eukaryotic initiation factor (eIF)4E. 4E-BP1
      complex in both control and septic rats. However, assembly of the active eIF4F
      complex as assessed by the association of eIF4E with eIF4G did not follow the
      pattern predicted by the increased availability of eIF4E resulting from changes
      in the phosphorylation of 4E-BP1. Indeed, sepsis caused a dramatic reduction in
      the amount of eIF4G associated with eIF4E in the presence or absence of insulin.
      Thus the inability of insulin to stimulate protein synthesis during sepsis may be
      related to a defect in signaling to a step in translation initiation involved in
      assembly of an active eIF4F complex.

PMID- 11595663
TI  - Aging skeletal muscle mitochondria in the rat: decreased uncoupling protein-3
      content.
AB  - The goal of the present study was to discern the cellular mechanism(s) that
      contributes to the age-associated decrease in skeletal muscle aerobic capacity.
      Skeletal muscle mitochondrial content, a parameter of oxidative capacity, was
      significantly lower (25 and 20% calculated on the basis of citrate synthase and
      succinate dehydrogenase activities, respectively) in 24-mo-old Fischer 344 rats
      compared with 6-mo-old adult rats. Mitochondria isolated from skeletal muscle of
      both age groups had identical state 3 (ADP-stimulated) and ADP-stimulated maximal
      respiratory rates and phosphorylation potential (ADP-to-O ratios) with both
      nonlipid and lipid substrates. In contrast, mitochondria from 24-mo-old rats
      displayed significantly lower state 4 (ADP-limited) respiratory rates and,
      consequently, higher respiratory control ratios. Consistent with the tighter
      coupling, there was a 68% reduction in uncoupling protein-3 (UCP-3) abundance in
      mitochondria from elderly compared with adult rats. Congruent with the
      respiratory studies, there was no age-associated decrease in carnitine
      palmitoyltransferase I and carnitine palmitoyltransferase II activities in
      isolated skeletal muscle mitochondria. However, there was a small, significant
      decrease in tissue total carnitine content. It is concluded that the in vivo
      observed decrease in skeletal muscle aerobic capacity with advanced age is a
      consequence of the decreased mitochondrial density. On the basis of the dramatic
      reduction of UCP-3 content associated with decreased state 4 respiration of
      skeletal muscle mitochondria from elderly rats, we propose that an increased free
      radical production might contribute to the metabolic compromise in aging.

PMID- 11595664
TI  - Parenteral nutrition with lipid or glucose suppresses liver growth and response
      to GH in adolescent male rats.
AB  - Our aim was to investigate the effects of modifying the carbohydrate-to-lipid
      ratio of parenteral nutrition (PN) on body composition and the anabolic actions
      of insulin-like growth factor I (IGF-I) and growth hormone (GH). Adolescent male
      Sprague-Dawley rats were randomized to receive 7 days of GH, IGF-I (3.5 mg. kg(
      1). day(-1) for both) or placebo while receiving high-carbohydrate PN (CHO-PN),
      high-lipid PN (L-PN), or an oral diet (chow) (the PN protocols were
      isonitrogenous and isocaloric). PN impaired muscle growth, which was reversed by
      GH in the CHO-PN group only (P < 0.03). PN increased carcass lipid (P < 0.02),
      the effect being greater in the L-PN than in the CHO-PN group (P < 0.001).
      Visceral lean tissue growth was significantly impaired by PN (P < 0.001). IGF-I
      reversed this impairment, but GH had no effect. PN impaired the normal increase
      in hepatic protein and DNA (P < 0.001) and produced liver steatosis (P < 0.001).
      However, this steatosis was less in L-PN than in CHO-PN (P < 0.001). Serum IGF-I
      and the acid-labile subunit (ALS) were decreased by PN (P < 0.001) and were not
      affected by GH during PN treatment. However, GH significantly increased serum ALS
      concentrations in the chow-fed rats (P = 0.032). In conclusion, modifying the CHO
      to-L ratio of PN had no significant effect on IGF-I action, but CHO-PN increased
      the peripheral effect of GH. L-PN increased carcass lipid significantly and
      decreased hepatic steatosis. Nevertheless, PN caused significant liver steatosis
      and profound impairment of hepatic cell growth, which was associated with
      relative hepatic GH resistance.

PMID- 11595665
TI  - Different role of insulin in GLUT-1 and -4 regulation in heart and skeletal
      muscle during perinatal hypothyroidism.
AB  - Two groups of hypothyroid rats were used; one group was given 2-mercapto-1
      methylimidazole (MMI) treatment in the drinking water of the mothers and was
      killed at 2 and 4 days of life, and the other group was given similar MMI
      treatment and then was thyroidectomized at 5 days of life and killed at 8 or 20
      days. Serum insulin, growth hormone (GH), and insulin-like growth factor I (IGF
      I) were decreased in MMI-treated rats but increased in MMI-treated plus
      thyroidectomized rats. No significant reduction of thyroid hormones was observed
      in 2-day-old MMI rats. Protein and mRNA expression of GLUT-1 increased, and those
      of GLUT-4 decreased, in the heart in all populations independent of changes in
      insulin, GH, and IGF-I levels. However, GLUT-4 protein and mRNA expression in
      quadriceps and gastrocnemius skeletal muscles decreased at 4 days and increased
      at 8 and 20 days of life in parallel with insulin, GH, and IGF-I levels. GLUT-1
      in the skeletal muscles seemed regulated posttranscriptionally and presented a
      decrease of mRNA expression in all stages studied. A differential sensitivity to
      insulin regulation of GLUT-1 and GLUT-4 glucose transporters seems to be one of
      the causes for the tissue-specific regulation of these glucose transporters in
      heart and skeletal muscles during the perinatal period.

PMID- 11595666
TI  - Chronic exposure to high leucine impairs glucose-induced insulin release by
      lowering the ATP-to-ADP ratio.
AB  - Exposure of rat pancreatic islets to 20 mM leucine for 24 h reduced insulin
      release in response to glucose (16.7 and 22.2 mM). Insulin release was normal
      when the same islets were stimulated with leucine (40 mM) or glyburide (1
      microM). To investigate the mechanisms responsible for the different effect of
      these secretagogues, we studied several steps of glucose-induced insulin
      secretion. Glucose utilization and oxidation rates in leucine-precultured islets
      were similar to those of control islets. Also, the ATP-sensitive K(+) channel
      independent pathway of glucose-stimulated insulin release, studied in the
      presence of 30 mM K(+) and 250 microM diazoxide, was normal. In contrast, the ATP
      to-ADP ratio after stimulation with 22.2 mM glucose was reduced in leucine
      exposed islets with respect to control islets. The decrease of the ATP-to-ADP
      ratio was due to an increase of ADP levels. In conclusion, prolonged exposure of
      pancreatic islets to high leucine levels selectively impairs glucose-induced
      insulin release. This secretory abnormality is associated with (and might be due
      to) a reduced ATP-to-ADP ratio. The abnormal plasma amino acid levels often
      present in obesity and diabetes may, therefore, affect pancreatic islet insulin
      secretion in these patients.

PMID- 11595667
TI  - Thyroid hormone induces cerebellar astrocytes and C6 glioma cells to secrete
      mitogenic growth factors.
AB  - In this study, the effect of thyroid hormone (triiodothyronine, T(3)) on the
      secretion of mitogenic growth factors in astrocytes and C6 glioma cells was
      examined. The proliferating activity of T(3) could be due, at least in part, to
      the astrocyte secretion of acidic and basic fibroblast growth factor (aFGF and
      bFGF), tumor necrosis factor-beta, and transforming growth factor-beta. In
      contrast, the conditioned medium (CM) of T(3)-treated C6 cells was mitogenic to
      this cell line only after hyaluronidase digestion, suggesting the impairment of
      growth factor mitogenic activity by hyaluronic acid. Furthermore, the presence of
      bFGF was significantly greater in the CM of both T(3)-treated astrocytes and T(3)
      treated C6 cells than in the corresponding control CM. These data show that T(3)
      induces cerebellar astrocytes to secrete mitogenic growth factors, predominantly
      bFGF, that could influence astrocyte and neuronal proliferation via autocrine and
      paracrine pathways.

PMID- 11595668
TI  - Methylation demand and homocysteine metabolism: effects of dietary provision of
      creatine and guanidinoacetate.
AB  - S-adenosylmethionine, formed by the adenylation of methionine via S
      adenosylmethionine synthase, is the methyl donor in virtually all known
      biological methylations. These methylation reactions produce a methylated
      substrate and S-adenosylhomocysteine, which is subsequently metabolized to
      homocysteine. The methylation of guanidinoacetate to form creatine consumes more
      methyl groups than all other methylation reactions combined. Therefore, we
      examined the effects of increased or decreased methyl demand by these
      physiological substrates on plasma homocysteine by feeding rats guanidinoacetate-
      or creatine-supplemented diets for 2 wk. Plasma homocysteine was significantly
      increased (~50%) in rats maintained on guanidinoacetate-supplemented diets,
      whereas rats maintained on creatine-supplemented diets exhibited a significantly
      lower (~25%) plasma homocysteine level. Plasma creatine and muscle total creatine
      were significantly increased in rats fed the creatine-supplemented or
      guanidinoacetate-supplemented diets. The activity of kidney L-arginine:glycine
      amidinotransferase, the enzyme catalyzing the synthesis of guanidinoacetate, was
      significantly decreased in both supplementation groups. To examine the role of
      the liver in mediating these changes in plasma homocysteine, isolated rat
      hepatocytes were incubated with methionine in the presence and absence of
      guanidinoacetate and creatine, and homocysteine export was measured. Homocysteine
      export was significantly increased in the presence of guanidinoacetate. Creatine,
      however, was without effect. These results suggest that homocysteine metabolism
      is sensitive to methylation demand imposed by physiological substrates.

PMID- 11595670
TI  - In vivo human lipolytic activity in preperitoneal and subdivisions of
      subcutaneous abdominal adipose tissue.
AB  - We studied eight normal-weight male subjects to examine whether the lipolytic
      rate of deep subcutaneous and preperitoneal adipose tissues differs from that of
      superficial abdominal subcutaneous adipose tissue. The lipolytic rates in the
      superficial anterior and deep posterior subcutaneous abdominal adipose tissues
      and in the preperitoneal adipose tissue in the round ligament were measured by
      microdialysis and (133)Xe washout under basal, postabsorptive conditions and
      during intravenous epinephrine infusion (0.15 nmol. kg(-1). min(-1)). Both in the
      basal state and during epinephrine stimulation, the superficial subcutaneous
      adipose tissue had higher interstitial glycerol concentrations than the two other
      depots. Similarly, the calculated glycerol outputs from the superficial depot
      were significantly higher than those from the deep subcutaneous and the
      preperitoneal depots. Thus, it is concluded that the lipolytic rate of the
      superficial subcutaneous adipose tissue on the anterior abdominal wall is higher
      than that of the deep subcutaneous adipose tissue on the posterior abdominal wall
      and that of the preperitoneal adipose tissue in the round ligament.

PMID- 11595669
TI  - Glucose uptake and glucose transporter proteins in skeletal muscle from
      undernourished rats.
AB  - Undernutrition in rats impairs secretion of insulin but maintains glucose
      normotolerance, because muscle tissue presents an increased insulin-induced
      glucose uptake. We studied glucose transporters in gastrocnemius muscles from
      food-restricted and control anesthetized rats under basal and euglycemic
      hyperinsulinemic conditions. Muscle membranes were prepared by subcellular
      fractionation in sucrose gradients. Insulin-induced glucose uptake, estimated by
      a 2-deoxyglucose technique, was increased 4- and 12-fold in control and food
      restricted rats, respectively. Muscle insulin receptor was increased, but
      phosphotyrosine-associated phosphatidylinositol 3-kinase activity stimulated by
      insulin was lower in undernourished rats, whereas insulin receptor substrate-1
      content remained unaltered. The main glucose transporter in the muscle, GLUT-4,
      was severely reduced albeit more efficiently translocated in response to insulin
      in food-deprived rats. GLUT-1, GLUT-3, and GLUT-5, minor isoforms in skeletal
      muscle, were found increased in food-deprived rats. The rise in these minor
      glucose carriers, as well as the improvement in GLUT-4 recruitment, is probably
      insufficient to account for the insulin-induced increase in the uptake of glucose
      in undernourished rats, thereby suggesting possible changes in other steps
      required for glucose metabolism.

PMID- 11595671
TI  - Intranasal inoculation with the olfactory bulb line variant of mouse hepatitis
      virus causes extensive destruction of the olfactory bulb and accelerated turnover
      of neurons in the olfactory epithelium of mice.
AB  - Viral upper respiratory infections are the most common cause of clinical
      olfactory dysfunction, but the pathogenesis of dysosmia after viral infection is
      poorly understood. Biopsies of the olfactory mucosa in patients that complain of
      dysosmia after viral infection fall into two categories: one in which no
      olfactory epithelium is seen and another in which the epithelium is disordered
      and populated mainly by immature neurons. We have used intranasal inoculation
      with an olfactory bulb line variant of MHV to study the consequences of viral
      infection on peripheral olfactory structures. MHV OBLV has little direct effect
      on the olfactory epithelium, but causes extensive spongiotic degeneration and
      destruction of mitral cells and interneurons in the olfactory bulb such that the
      axonal projection from the bulb via the lateral olfactory tract is markedly
      reduced. Moreover, surviving mitral cells apparently remain disconnected from the
      sensory neuron input to the glomerular layer, judging from retrograde labeling
      studies using Dil. The damage to the bulb indirectly causes a persistent, long
      term increase in the turnover of sensory neurons in the epithelium, i.e. the
      relative proportion of immature to mature sensory neurons and the rate of basal
      cell proliferation both increase. The changes that develop after inoculation with
      MHV OBLV closely resemble the disordering of the olfactory epithelium in some
      patient biopsies. Thus, damage to the olfactory nerve or bulb may contribute to a
      form of post-viral olfactory dysfunction and MHV OBLV is a useful model for
      studying the pathogenesis of this form of dysosmia.

PMID- 11595672
TI  - Functional consequences following infection of the olfactory system by intranasal
      infusion of the olfactory bulb line variant (OBLV) of mouse hepatitis strain JHM.
AB  - The present study assessed the functional consequences of viral infection with a
      neurotropic coronavirus, designated MHV OBLV, that specifically targets central
      olfactory structures. Using standard operant techniques and a 'go, no-go'
      successive discrimination paradigm, six BALB/c mice were trained to discriminate
      between the presentation of an air or odor stimulus (three mice for each of the
      odorants propanol and propyl acetate). Two additional BALB/c mice were trained to
      discriminate between the presentation of air and the presentation of either
      vanillin or propionic acid. Following criterion performance, each mouse received
      an additional 2000 trials of overtraining. At completion of overtraining one
      mouse from the propanol and propyl acetate groups were allocated as untreated.
      The remaining six mice were inoculated with 300 microl of the OBLV stock per
      nostril for a total of 1.5 x 10(6) p.f.u. in 600 microl. Following a 1 month
      rest, untreated and inoculated animals were again tested on their respective air
      versus odor discrimination task. Untreated animals immediately performed at
      criterion levels. In contrast, inoculated animals varied in their capacity to
      discriminate between air and odorant. Five of the six inoculated mice showed
      massive disruption of the olfactory bulb, including death of mitral cells; the
      other was more modestly affected. In addition, the density of innervation of the
      olfactory mucosa by substance P-containing trigeminal fibers is also affected by
      inoculation. Those mice that remained anosmic to the training odorants had the
      most severe reduction in mitral cell number and substance P fiber density among
      the inoculated animals.

PMID- 11595673
TI  - Amiloride blocks salt taste transduction of the glossopharyngeal nerve in
      metamorphosed salamanders.
AB  - Studies in the last two decades have shown that amiloride-sensitive Na(+)
      channels play a role in NaCl transduction in rat taste receptors. However, this
      role is not readily generalized for salt taste transduction in vertebrates,
      because functional expression of these channels varies across species and also in
      development in a species. Glossopharyngeal nerve responses to sodium and
      potassium salts were recorded in larval and metamorphosed salamanders and
      compared before and after the oral floor was exposed to amiloride, a blocker of
      Na(+) channels known to be responsible for epithelial ion transport. Pre-exposure
      to amiloride (100 microM) did not affect salt taste responses in both axolotls
      (Ambystoma mexicanum) and larval Ezo salamanders (Hynobius retardatus). In
      contrast, in metamorphosed Ezo salamanders the nerve responses to NaCl were
      significantly reduced by amiloride. In amphibians amiloride-sensitive components
      in salt taste transduction seem to develop during metamorphosis.

PMID- 11595674
TI  - Volumetric and horseradish peroxidase tracing analysis of rat olfactory bulb
      following reversible olfactory nerve lesions.
AB  - Olfactory receptor neurons can regenerate from basal stem cells. Receptor neuron
      lesion causes degenerative changes in the olfactory bulb followed by regeneration
      as new olfactory receptor axons innervate the olfactory bulb. To our knowledge,
      parametric analyses of morphometric changes in the olfactory bulb during
      degeneration and regeneration do not exist except in abstract form. To better
      characterize olfactory bulb response, we performed morphometric analysis in rats
      following reversible olfactory nerve lesion with diethyldithiocarbamate. We also
      performed anterograde tracing of the olfactory nerve with wheatgerm agglutinin
      linked to horseradish peroxidase. Results of morphometry and tracing were
      complementary. The glomerular layer and external plexiform layer showed shrinkage
      of 45 and 26%, respectively, at 9 days. No significant shrinkage occurred in any
      other layer. Individual glomeruli shrank by 40-50% at 3 and 9 days following
      lesion. These data show that degenerative changes occur both in the glomeruli and
      transneuronally in the external plexiform layer. Olfactory nerve regeneration
      (identified by WGA-HRP transport) paralleled volumetric recovery. Recovery
      occurred first in ventral and lateral glomeruli between 9 and 16 days followed by
      recovery in medial and dorsal glomeruli. These data indicate substantial
      transynaptic degeneration in the olfactory bulb and a heretofore unrecognized
      gradient in olfactory nerve regeneration that can be used to systematically study
      recovery of a cortical structure.

PMID- 11595675
TI  - Taste-enhancing effects of glycine on the sweetness of glucose: a gustatory
      aspect of symbiosis between the ant, Camponotus japonicus, and the larvae of the
      lycaenid butterfly, Niphanda fusca.
AB  - The lycaenid butterfly, Niphanda fusca, has a parasitic relationship with its
      host ant, Camponotus japonicus: the caterpillars may use chemical mimicry to
      enter the ant nest where they are fed mouth-to-mouth by the adult ants until
      pupation. Nevertheless, larvae offer their host ants a nutritious secretion that
      contains 160 mM glucose and 43 mM glycine. Using glucose and glycine mixture as
      artificial secretions, we investigated the gustatory effect of glucose and/or
      glycine on the ants. Glycine induced neither feeding behavior nor gustatory
      response in the ants if its concentration was <500 mM. In the presence of glycine
      at the concentration in the secretion, however, the ants improved their
      preference to glucose, and the sugar receptor cell exhibited electrophysiological
      enhancement of response to glucose in a glycine-concentration-dependent manner.
      By adding glycine to glucose in their secretions, therefore, the butterfly larvae
      can manipulate the gustatory sense of the ants. The alluring taste of 'glycine
      flavored glucose' could motivate the host ants to feed the larvae and thereby
      receive the secretions as a reward. The taste enhancement created by the
      combination of sugar and amino acid may play a role in the evolution of the
      parasitic relationships of these insects. The taste-enhancing effect appears to
      be analogous to taste enhancement by 'umami' substances in humans.

PMID- 11595676
TI  - Binary taste mixture interactions in prop non-tasters, medium-tasters and super
      tasters.
AB  - It is generally assumed that the mutual, but asymmetric, suppression of the
      components in binary taste mixtures is an invariant property of the human
      psychophysical response to such mixtures. However, taste intensities have been
      shown to vary as a function of individual differences in sensitivity, indexed by
      the perceived bitterness of 6-n-propylthiouracil (PROP). To determine if these
      variations in taste perception influence taste mixture interactions, groups of
      PROP super-, medium- and non-tasters assessed four binary taste mixtures: sweet
      bitter [sucrose/quinine hydrochloride (QHCl)], sweet-sour (sucrose/citric acid),
      salty-bitter (NaCl/QHCl) and salty-sour (NaCl/citric acid). In each experiment,
      subjects received factorial combinations of four levels of each of two tastants
      and rated individual taste intensities and overall mixture intensity. For each
      taste quality, super-tasters typically gave higher ratings than either medium- or
      non-tasters, who tended not to differ. There were also group differences in the
      interactions of the mixtures' components. Super-tasters rated the overall
      intensity of the mixtures, most likely reflecting integration of the taste
      components, as greater than medium- and non-tasters, who again showed few
      differences. In sweet-bitter mixtures, non-tasters failed to show the suppression
      of sweetness intensity by the highest QHCl concentration that was evident in
      super- and medium-tasters. These data show that the perception of both tastes and
      binary taste mixture interactions varies as a function of PROP taster status, but
      that this may only be evident when three taster groups are clearly distinguished
      from one another.

PMID- 11595677
TI  - Orbital response indicates nasal pungency: analysis of biomechanical strain on
      the skin.
AB  - Stimulation of the human nasal passage with pungent vapor elicits motor responses
      in a zone around the eye. This investigation addressed whether quantification of
      such responses, particularly activity of the orbicularis oculi muscle, could
      yield a sensitive index of nasal pungency. We placed an array of small, high
      contrast targets just beneath the lower eyelid and videotaped their movement to
      capture deformation of the skin atop the orbicularis oculi during 3 s stimulation
      with pungent concentrations of ethyl acetate. Eleven subjects participated.
      Analysis of the movements served to determine mechanical strain, which yielded a
      single index that we termed 'maximum strain'. This increased with concentration
      of the vapor and with time during and just after stimulation. Comparison with
      psychophysical data showed that the strain became evident at concentrations just
      detectable as pungent. Maximum strain measured on the skin shows promise as an
      objective index of pungency.

PMID- 11595678
TI  - Determination of saltiness from the laws of thermodynamics--estimating the gas
      constant from psychophysical experiments.
AB  - One can relate the saltiness of a solution of a given substance to the
      concentration of the solution by means of one of the well-known psychophysical
      laws. One can also compare the saltiness of solutions of different solutes which
      have the same concentration, since different substances are intrinsically more
      salty or less salty. We develop here an equation that relates saltiness both to
      the concentration of the substance (psychophysical) and to a distinguishing
      physical property of the salt (intrinsic). For a fixed standard molar entropy of
      the salt being tasted, the equation simplifies to Fechner's law. When one allows
      for the intrinsic 'noise' in the chemoreceptor, the equation generalizes to
      include Stevens's law, with corresponding decrease in the threshold for taste.
      This threshold reduction exemplifies the principle of stochastic resonance. The
      theory is validated with reference to experimental data.

PMID- 11595679
TI  - Spiking properties of olfactory receptor cells in the slice preparation.
AB  - The whole-cell, patch clamp [corrected] method was applied to olfactory receptor
      cells in slice preparations made from bullfrog olfactory epithelium. Under
      voltage-clamp conditions, olfactory receptor cells showed a transient inward
      current followed by a steady outward current in response to depolarizing voltage
      steps, as has been shown in the isolated preparation. The input resistance was
      5.4 +/- 3.9 GOmega and capacitance 21.9 +/- 9.7 pF. Under current-clamp
      conditions, depolarization of cells by current injection induced action
      potentials. In 13 out of 20, spike generation was repetitive with a maximum
      frequency of 24 Hz. The frequency of the repetitive discharges increased as the
      injected current was increased. The relationship between the size of the injected
      current and firing frequency could be well fitted by the Michaelis-Menten
      equation, indicating that the spike generation site lacks the non-linear boosting
      system. The slice preparation developed here would provide a powerful tool to
      study the spike encoding system of the olfactory receptor cells.

PMID- 11595681
TI  - Telomerase and cancer: where and when?

PMID- 11595682
TI  - Where to next with retinoids for cancer therapy?

PMID- 11595683
TI  - A novel approach in the treatment of cancer: targeting the epidermal growth
      factor receptor.
AB  - The epidermal growth factor receptor (EGFR) autocrine pathway contributes to a
      number of processes important to cancer development and progression, including
      cell proliferation, apoptosis, angiogenesis, and metastatic spread. The critical
      role the EGFR plays in cancer has led to an extensive search for selective
      inhibitors of the EGFR signaling pathway. The results of a large body of
      preclinical studies and the early clinical trials thus far conducted suggest that
      targeting the EGFR could represent a significant contribution to cancer therapy.
      A variety of different approaches are currently being used to target the EGFR.
      The most promising strategies in clinical development include monoclonal
      antibodies to prevent ligand binding and small molecule inhibitors of the
      tyrosine kinase enzymatic activity to inhibit autophosphorylation and downstream
      intracellular signaling. At least five blocking monoclonal antibodies have been
      developed against the EGFR. Among these, IMC-225 is a chimeric human-mouse
      monoclonal IgG1 antibody that has been the first anti-EGFR targeted therapy to
      enter clinical evaluation in cancer patients in Phase II and III studies, alone
      or in combination with conventional therapies, such as radiotherapy and
      chemotherapy. A number of small molecule inhibitors of the EGFR tyrosine kinase
      enzymatic activity is also in development. OSI-774 and ZD1839 (Iressa) are
      currently in Phase II and III development, respectively. ZD1839, a p.o. active,
      selective quinazoline derivative has demonstrated promising in vitro and in vivo
      antitumor activity. Preliminary results from Phase I and II trials in patients
      with advanced disease demonstrate that ZD1839 and OSI-774 have an acceptable
      tolerability profile and promising clinical efficacy in patients with a variety
      of tumor types. This mini-review describes the EGFR inhibitors in clinical
      development.

PMID- 11595684
TI  - Sequential tumor biopsies in early phase clinical trials of anticancer agents for
      pharmacodynamic evaluation.
AB  - PURPOSE: In the setting of target-based anticancer drug development, it is
      critical to establish that the observed preclinical activity can be attributed to
      modulation of the intended target in early phase trials in human subjects. This
      paradigm of target modulation allows us to determine a Phase II or III dose
      (optimal biochemical/biological modulatory dose) that may not necessarily be the
      maximum tolerated dose. A major obstacle to target-based (often cytostatic) drug
      development has been obtaining relevant tumor tissue during clinical trials of
      these novel agents for laboratory analysis of the putative marker of drug effect.
      EXPERIMENTAL DESIGN: From 1989 to present, we have completed seven clinical
      trials in which the end point was a biochemical or biological modulatory dose in
      human tumor tissues (not surrogate tissue). Eligibility enrollment required that
      patients have a biopsiable lesion either with computerized tomography (CT)
      guidance or direct visualization and consent to sequential (pre and
      posttreatment) biopsies. RESULTS: A total of 192 biopsies were performed in 107
      patients. All but 8 patients had sequential pre and posttreatment biopsies.
      Seventy-eight (73%) of the 107 patients had liver lesion biopsies. In eight
      patients, either one or both biopsies contained insufficient viable tumor tissue
      or no tumor tissue at all for analysis. Of a total of 99 patients in whom we
      attempted to obtain paired biopsies, a total of 87 (88%) were successful. Reasons
      for failure included patient refusal for a second biopsy (n = 2), vasovagal
      reaction with first biopsy precluding a second biopsy (n = 1), subcapsular
      hepatic bleeding (n = 1), and most commonly obtaining necrotic tumor, fibrous, or
      normal tissue in one of the two sequential biopsies (n = 8). CONCLUSIONS: This is
      the first and largest reported series demonstrating that with adequate
      precautions and experience, sequential tumor biopsies are feasible and safe
      during early phase clinical trials.

PMID- 11595685
TI  - Serum osteoprotegerin levels are increased in patients with advanced prostate
      cancer.
AB  - PURPOSE: Osteoprotegerin (OPG) is a soluble osteoclastogenesis inhibitor that
      regulates bone turnover. We reported recently that OPG protein expression is
      significantly increased in prostate cancer (CaP) cells present in bone
      metastases. The aim of this study was to determine serum OPG levels in patients
      at different stages of CaP and correlate the results with disease status.
      EXPERIMENTAL DESIGN: OPG levels were examined in patients with benign prostatic
      hyperplasia, clinically localized CaP, early recurrence of CaP, and advanced CaP
      and evidence of bone metastases. Serum OPG levels were measured by sandwich ELISA
      assays. The serum Crosslaps (sCTX) assay was used to quantify bone resorption in
      the advanced CaP group. RESULTS: Serum OPG levels were increased significantly in
      the advanced CaP group versus all other groups. There was no significant
      correlation between serum OPG levels and PSA levels either in the advanced CaP
      group or within any of three treatment subclasses of this group: no Tx, those not
      treated; Tx, those treated; and R, those treated with resorption blockers. Levels
      of OPG were negatively correlated with sCTX levels only in the advanced CaP Tx
      group. sCTX levels correlated with prostate-specific antigen levels in the
      advanced CaP Tx and R groups but not in the no-Tx group. CONCLUSIONS: Our data
      show that serum OPG levels are increased with advanced CaP. We hypothesize that
      OPG levels are related to CaP progression and suggest that further studies of the
      biological effects of OPG on CaP metastases are warranted.

PMID- 11595686
TI  - Correlation of p53 mutations with resistance to platinum-based chemotherapy and
      shortened survival in ovarian cancer.
AB  - PURPOSE: The p53 tumor suppressor gene plays a central role in cell cycle
      regulation and induction of apoptosis. We analyzed p53 alterations and their
      impact on response to chemotherapy and clinical outcome in ovarian cancer
      patients. EXPERIMENTAL DESIGN: One hundred seventy-eight ovarian carcinomas, snap
      frozen and stored at -80 degrees C, were analyzed for mutations of the p53 gene
      (exons 2-11) by single-strand conformation polymorphism and DNA sequencing and
      for p53 overexpression by immunohistochemistry (monoclonal antibody DO7).
      RESULTS: p53 mutations were found in 56% (99 of 178) of the tumors, and 62% of
      these were located in evolutionary highly conserved domains of the gene. Time to
      progression and overall survival were significantly shortened in patients with
      p53 mutations compared with wild-type p53 (P = 0.029 and P = 0.014) and patients
      with mutations in highly conserved domains as opposed to nonconserved domains or
      wild-type p53 (P = 0.010 and P = 0.007). p53 protein overexpression (>10%
      positively stained nuclei) was found in 62% (110 of 178). Time to progression and
      overall survival were shorter in cases with p53 overexpression (cutpoint, 10%: P
      = 0.071 and P = 0.056) but only marginally significant. Resistance to adjuvant
      cisplatin or carboplatin chemotherapy was significantly more frequent in patients
      with p53 overexpression (P = 0.001) or p53 missense mutations (P = 0.008) than
      patients with normal p53. CONCLUSIONS: p53 alterations correlate significantly
      with resistance to platinum-based chemotherapy, early relapse, and shortened
      overall survival in ovarian cancer patients in univariate analysis. In
      multivariable analysis though, p53 was not an independent prognostic factor.

PMID- 11595687
TI  - A selective cyclooxygenase-2 inhibitor, NS-398, enhances the effect of radiation
      in vitro and in vivo preferentially on the cells that express cyclooxygenase-2.
AB  - It has been proposed that Cyclooxygenase (COX)-2 inhibitors may be able to
      enhance the effects of chemotherapeutic or radiation treatment; however,
      currently few studies have been reported that define the radiation-enhancing
      effect of COX-2 inhibitors. We conducted in vitro radiation survival experiments
      using rat intestinal epithelial cells which were stably transfected with COX-2
      cDNA in the sense (RIE-S) and antisense (RIE-AS) orientations to investigate the
      potential radiosensitizing effect of the selective COX-2 inhibitor, NS-398.
      Apoptosis was measured using 7-aminoactinomycin-D with flow cytometry to
      investigate underlying mechanisms for the effect of NS-398 on radiosensitivity.
      The same experiments were repeated with NCI-H460 human lung cancer cells, which
      express COX-2 constitutively, and HCT-116 human colon cancer cells, which lack
      COX-2 expression. In vivo tumor growth delay assays were also performed with
      tumors formed by H460 and HCT-116 cells. No difference was observed in the
      intrinsic radiation sensitivity of RIE-S and RIE-AS cells exposed to radiation
      alone. However, 150-400 microM of NS-398 enhanced radiosensitivity in a
      concentration-dependent manner in RIE-S cells with dose enhancement ratios of 1.2
      1.9 at a surviving fraction of 0.25. However, this effect was not shown in RIE-AS
      cells. NS-398 enhanced radiosensitivity in H460 cells with a dose enhancement
      ratio of 1.8 but protected HCT-116 cells from the effects of radiation. Radiation
      induced apoptosis was enhanced by NS-398 in RIE-S and H460 cells but not in RIE
      AS and HCT-116 cells. Additionally, this radiation-enhancing effect in RIE-S
      cells seemed to be attributable to some mechanisms other than the reversal of
      radioresistance induced by COX-2. NS-398 (36 mg/kg) enhanced the effect of
      radiation on H460 tumors in vivo by an enhancement factor of 2.5; however, it did
      not enhance the radiosensitivity of HCT-116 tumors (enhancement factor = 1.04).
      These in vitro and in vivo results suggest that selective COX-2 inhibitors
      enhance the effect of radiation on tumors that express COX-2 but not on COX-2
      lacking tumors. This effect may be attributable to enhancement of radiation
      induced apoptosis. Thus, selective COX-2 inhibitors may have potential as
      radiosensitizers for treatment of human cancers.

PMID- 11595688
TI  - Induction of apoptosis of integrin-expressing human prostate cancer cells by
      cyclic Arg-Gly-Asp peptides.
AB  - Prostate cancer is the second most common cause of cancer deaths among men in the
      United States. We have investigated the effect of cyclo-(Arg-Gly-Asp-D-Phe-Val;
      cRGDfV), Arg-Gly-Asp, or Arg-Gly-Asp-Ser, on survival of human prostate cancer
      (LNCaP and PC-3) and normal (HEL) cells in vitro. Addition of cRGDfV (20
      microg/ml) but not the linear Arg-Gly-Asp or Arg-Gly-Asp-Ser peptide induced
      significant (approximately 84%) killing of LNCaP cells expressing alphavbeta3
      integrins on their surfaces. In contrast, none of these peptides had any major
      effect on the growth of PC-3 or HEL cells, which express little alphavbeta3
      integrin on their surfaces. Treatment of LNCaP but not of PC-3 or HEL cells with
      cRGDfV resulted in cleavage of focal adhesion kinase, a key player in integrin
      mediated signal transduction pathway. The evidence we present here suggests that
      the killing of LNCaP cells after cRGDfV treatment was attributable to apoptosis
      or programmed cell death. This is evidenced by activation of at least two
      caspases (caspase-3 and caspase-9) as detected by cleavage of poly(ADP-ribose)
      polymerase and partial blocking of apoptosis by a selective inhibitor of caspase
      9. Our results suggest that cRGDfV may be an effective treatment for some human
      prostate cancers by inducing apoptosis through interference with the regulation
      of integrin/focal adhesion kinase-mediated signal transduction pathway necessary
      for cell survival.

PMID- 11595689
TI  - Phase I trial of a melanoma vaccine with gp100(280-288) peptide and tetanus
      helper peptide in adjuvant: immunologic and clinical outcomes.
AB  - A melanoma vaccine composed of HLA-A2-restricted peptide YLEPGPVTA (gp100(280)),
      with or without a modified T-helper epitope from tetanus toxoid AQYIKANSKFIGITEL,
      has been evaluated in a Phase I trial to assess safety and immunological
      response. The vaccines were administered s.c. in either of two adjuvants,
      Montanide ISA-51 or QS-21, to 22 patients with high-risk resected melanoma (stage
      IIB-IV). Local and systemic toxicities were mild and transient. We detected CTL
      responses to the gp100(280) peptide in peripheral blood in 14% of patients.
      Helper T-cell responses to the tetanus helper peptide were detected in 79% of
      patients and had a Th1 cytokine profile. One patient with a CTL response to gp100
      had a recurrence in a lymph node 2 years later; her nodes contained CD8+ cells
      reactive to gp100(280) (0.24%), which proliferated in response to peptide. The
      overall survival of patients is 75% (95% confidence interval, 57-94%) at 4.7
      years follow-up, which compares favorably with expected survival. Four of 14
      patients who completed at least six vaccines subsequently developed metastases,
      all of which were solitary and surgically resectable. They remain alive and
      clinically free of disease at last follow-up. Data from this trial demonstrate
      immunogenicity of the gp100(280) peptide and suggest that immune responses may
      persist long-term in some patients. The frequency and magnitude of the CTL
      response may be improved with more aggressive vaccination regimens. Although this
      Phase I study was not intended to evaluate clinical benefit, the excellent
      survival of patients on this protocol suggests the possibility of a benefit that
      should be assessed in future studies.

PMID- 11595690
TI  - Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant
      paclitaxel chemotherapy.
AB  - PURPOSE: Neoadjuvant chemotherapy for breast cancer creates new possibilities for
      the analysis of biological factors in the tumor and/or host, which may play a
      role in the response to treatment. In this study we analyzed whether changes in
      local antitumor immunity take place after neoadjuvant paclitaxel therapy and if
      they correlate with response to treatment. EXPERIMENTAL DESIGN: Neoadjuvant
      chemotherapy (paclitaxel, 200 mg/m2 q2w, 4 treatments) was followed by definitive
      surgical management. Histological sections from the pre- and post-treatment
      surgical specimens of 25 patients were analyzed for the extent of lymphocytic
      infiltration and presence of tumor infiltrating lymphocytes (TILs). The
      cumulative apoptotic response in the tumor after the first dose of paclitaxel was
      also studied in 10 of 25 patients. RESULTS: Pretreatment lymphocytic infiltrate
      in the tumor was minimal in the majority of patients and showed no relationship
      with clinical response. In the patients without TILs before treatment,
      development of TILs after treatment was noted in 0/3 (0%) patients with stable
      disease, 3/12 (25%) patients with clinical partial response, and 4/6 (67%)
      patients with clinical complete response and pathological residual disease. These
      correlated with the tumor cell apoptotic response to the first dose of
      paclitaxel. CONCLUSIONS: These results suggest that development of TILs after
      treatment correlates with clinical response to neoadjuvant paclitaxel therapy.
      The possible mechanism(s) whereby neoadjuvant chemotherapy may lead to induction
      of antitumor T cells is discussed. Immunological processes may influence the
      response of breast cancer patients to neoadjuvant treatment.

PMID- 11595691
TI  - Clinical and molecular responses in high-grade intraepithelial neoplasia treated
      with topical imiquimod 5%.
AB  - OBJECTIVE: To assess the clinical and molecular response of patients with
      recurrent high-grade vulvar, vaginal, or cervical intraepithelial neoplasia
      treated with topical 1-2(2-methylpropyl)-1H-imidazo [4,5-c] quinolin-4-amine
      (imiquimod) cream 5%, an immune response modifier with known efficacy in the
      treatment of external genital warts. METHODS: This is the first case series in
      the peer-reviewed literature reporting the use of imiquimod in high-grade
      intraepithelial neoplasia of the lower genital tract. Eight patients with high
      grade intraepithelial neoplasia were treated with imiquimod in the gynecological
      oncology clinic and the HIV gynecology clinic at The University of Texas Medical
      Branch at Galveston. Frozen biopsies were available for RNA extraction on four
      patients before and after therapy. Using semiquantitative reverse transcription
      PCR, we measured RNA levels of IFNs alpha and gamma, 2',5'-oligoadenylate
      synthetase, as well as CD4 and CD8 lymphocyte markers. RESULTS: Of the patients
      treated, four had complete responses, two had partial responses, one progressed,
      and one did not tolerate the therapy. Of the four complete responders, two
      remained disease-free (mean follow-up, 33 months). 2',5'-Oligoadenylate
      synthetase RNA expression showed an increased trend after therapy. CONCLUSIONS:
      These results obtained in this small and heterogeneous group merit further study
      in the use of topical 5% imiquimod use in the treatment of intraepithelial
      neoplasia. An important mechanism of action of imiquimod may involve 2',5'
      oligoadenylate synthetase antiviral activity.

PMID- 11595692
TI  - A phase I trial and pharmacokinetic study of 9-cis-retinoic acid (ALRT1057) in
      pediatric patients with refractory cancer: a joint Pediatric Oncology Branch,
      National Cancer Institute, and Children's Cancer Group study.
AB  - PURPOSE: To determine the maximum tolerated dose and describe the toxicities of 9
      cis-retinoic acid (9cRA, ALRT1057) administered p.o. tid in pediatric patients
      with refractory cancer and to study the pharmacokinetics of 9cRA and determine
      whether systemic drug exposure changes with chronic dosing. PATIENTS AND METHODS:
      Children with refractory cancer (stratified by age, < or =12 and >12 years) were
      treated with p.o. 9cRA for 28 consecutive days. The starting dose was 50
      mg/m(2)/day divided into 3 doses with planned escalations to 65, 85, and 110
      mg/m(2)/day. Pharmacokinetic sampling was performed on days 1 and 29 of the first
      cycle. RESULTS: Of the 37 patients entered, 18 patients < or =12 years of age and
      11 patients >12 years of age were evaluable for toxicity. In patients >12 years
      of age, dose-limiting headache occurred in 2/2 patients at the 110 mg/m(2)/day
      dose level; 1/8 patients at 85 mg/m(2)/day developed dose-limiting pseudotumor
      cerebri. In patients < or =12 years of age, 3/5 patients at the starting dose
      level of 50 mg/m(2)/day developed dose-limiting pseudotumor cerebri; and 0/6
      patients experienced dose-limiting toxicity at 35 mg/m(2)/day. Reversible non
      dose-limiting hepatotoxicity was observed in 15 patients across all of the dose
      levels. There was considerable interpatient variability in 9cRA plasma
      concentrations. Peak plasma concentrations of 9cRA occurred at a median of 1.5 h
      after a p.o. dose, and the harmonic-mean terminal half-life was 43 min. By day 29
      of 9cRA administration, the plasma 9cRA area under the curve declined by an
      average of 65% from day 1 values. CONCLUSIONS: The dose-limiting toxicity of 9cRA
      in pediatric patients was neurotoxicity, primarily pseudotumor cerebri. Younger
      children tolerate significantly lower doses of 9cRA than older children. Similar
      to all-trans-retinoic acid, the pharmacokinetics of 9cRA demonstrated a wide
      degree of interpatient variability and decreased over time when administered on a
      daily basis. The recommended Phase II dose of 9cRA in patients < or =12 and >12
      years of age is 35 and 85 mg/m(2)/day, respectively.

PMID- 11595693
TI  - Phase I study of doxil-cisplatin combination chemotherapy in patients with
      advanced malignancies.
AB  - PURPOSE: Our first objective was to evaluate the feasibility of administering a
      combination of Doxil, a pegylated liposome formulation of doxorubicin, and
      cisplatin and to determine the maximum tolerated dose of the combination. A
      secondary objective was to examine Doxil peak and 7-day postinjection plasma
      levels at the various dose levels tested. METHODS: Patients with advanced solid
      tumors were treated every 4 weeks with cisplatin on day 1 and Doxil on day 2. In
      the first three dose levels, the dose of Doxil was fixed at 40 mg/m(2), whereas
      the dose of cisplatin was escalated from 40 to 50 and 60 mg/m(2). At the fourth
      and fifth dose levels, the dose of cisplatin was fixed at 60 mg/m(2), whereas the
      dose of Doxil was escalated to 50 and to 60 mg/m(2). Plasma Doxil (doxorubicin
      equivalent) levels were measured by a high-performance liquid chromatography
      assay with fluorescence detection at 1 h and 7 days after infusion of Doxil.
      RESULTS: Twenty-six patients entered the study. Twenty-four patients completed a
      minimum of 2 courses and were fully assessable for toxicity and efficacy.
      Eighteen patients had received prior chemotherapy, 11 of them with anthracycline
      containing regimens. A total of 177 courses were administered within the study.
      In 12 patients, cisplatin was discontinued after 1 to 13 courses, and Doxil was
      continued alone for 1-22 courses. All other patients received both drugs until
      discontinuation of therapy. The dose-limiting toxicities were neutropenia and
      mucositis. Grade 4 neutropenia was seen in 3 patients (one with neutropenic
      fever) at dose levels 4 and 5. Grade 3 mucositis was observed in 4 patients at
      dose levels 3, 4, and 5. In contrast, the most severe palmar-plantar
      erythrodysesthesia manifestation was grade 2 seen in 1 patient only. Tumor
      responses included seven partial responses, of which three were in ovarian cancer
      patients. In four of seven responders, the time to disease progression exceeded 1
      year. Doxil 1-h (C(max) equivalent) levels were assessed in 20 patients. The mean
      Doxil C(max) (mg/l plasma) increased gradually with dose escalation from 14.7 +/-
      1.9 for 40 mg/m(2), to 17.3 +/- 3.0 for 50 mg/m(2), and 23.3 +/- 5.5 for 60
      mg/m(2). The 60 mg/m(2) C(max) was similar to data obtained in parallel clinical
      studies at our institution with single-agent Doxil at 60 mg/m(2). However, the 7
      day Doxil postinfusion levels were significantly lower in patients receiving the
      Doxil-cisplatin combination than in those receiving single-agent Doxil.
      CONCLUSION: Doxil can be administered at full maximum tolerated dose (50 mg/m(2)
      every 4 weeks) in combination with 60 mg/m(2) cisplatin, with no evidence of
      major overlapping toxicities. Palmar-plantar erythrodysesthesia incidence and
      severity appears to be diminished, in comparison with data available for single
      agent Doxil. Plasma concentration data point to an accelerated clearance of Doxil
      when administered after cisplatin.

PMID- 11595694
TI  - A Phase I clinical and pharmacological evaluation of sodium phenylbutyrate on an
      120-h infusion schedule.
AB  - PURPOSE: Sodium phenylbutyrate (PB) demonstrates potent differentiating capacity
      in multiple hematopoietic and solid tumor cell lines. We conducted a Phase I and
      pharmacokinetic study of PB by continuous infusion to characterize the maximum
      tolerated dose, toxicities, pharmacokinetics, and antitumor effects in patients
      with refractory solid tumors. PATIENTS AND METHODS: Patients were treated with a
      120-h PB infusion every 21 days. The dose was escalated from 150 to 515
      mg/kg/day. Pharmacokinetics were performed during and after the first infusion
      period using a validated high-performance liquid chromatographic assay and single
      compartmental pharmacokinetic model for PB and its principal metabolite,
      phenylacetate. RESULTS: A total of 24 patients were enrolled on study, with
      hormone refractory prostate cancer being the predominant tumor type. All patients
      were evaluable for toxicity and response. A total of 89 cycles were administered.
      The dose-limiting toxicity (DLT) was neuro-cortical, exemplified by excessive
      somnolence and confusion and accompanied by clinically significant hypokalemia,
      hyponatremia, and hyperuricemia. One patient at 515 mg/kg/day and another at 345
      mg/kg/day experienced this DLT. Toxicity resolved < or =12 h of discontinuing the
      infusion. Other toxicities were mild, including fatigue and nausea. The maximum
      tolerated dose was 410 mg/kg/day for 5 days. Pharmacokinetics demonstrated that
      plasma clearance of PB increased in a continuous fashion beginning 24 h into the
      infusion. In individuals whose V(max) for drug elimination was less than their
      drug-dosing rate, the active metabolite phenylacetate accumulated progressively.
      Plasma PB concentrations (at 410 mg/kg/day) remained above the targeted
      therapeutic threshold of 500 micromol/liter required for in vitro activity.
      CONCLUSION: The DLT in this Phase I study for infusional PB given for 5 days
      every 21 days is neuro-cortical in nature. The recommended Phase II dose is 410
      mg/kg/day for 120 h.

PMID- 11595695
TI  - Phase I and pharmacological study of a new camptothecin derivative, exatecan
      mesylate (DX-8951f), infused over 30 minutes every three weeks.
AB  - PURPOSE: A Phase I study of exatecan, a new water-soluble camptothecin
      derivative, was conducted to determine the maximum tolerated dose and a
      recommended dose, according to an internationally standardized core protocol.
      Pharmacological profiles of lactone and total (lactone + carboxylate) exatecan
      were also investigated. PATIENTS AND METHODS: Fifteen patients with advanced
      solid malignancies were treated with 3, 5, and 6.65 mg/m(2) of exatecan infused
      over 30 min every 3 weeks. Concentrations of lactone, total drug, and a
      metabolite in plasma and urine were determined during the first course. RESULTS:
      Dose-limiting neutropenia and liver dysfunction were observed in two of six
      patients at 6.65 mg/m(2), but no grade 3 or worse diarrhea was observed. Emesis
      was moderate, and no grade 3 or worse nausea and vomiting were observed at a
      recommended dose of 5 mg/m(2), with prophylactic use of granisetron.
      Pharmacokinetics were linear and had moderate variability; clearances of lactone
      and total drug were 6.8 +/- 2.8 and 2.1 +/- 1.1 (mean +/- SD) l/h/m(2),
      respectively. The ratio of lactone concentration to total drug concentration in
      plasma decreased from 0.81 +/- 0.06 at the end of infusion to 0.15 +/- 0.06 10 h
      after the infusion. The lactone:total ratio of drug exposure was 0.30 +/- 0.08,
      ranging from 0.16 to 0.43. Neutropenia was related to the drug exposure of both
      lactone and total drug. CONCLUSIONS: The recommended dose of exatecan infused
      over 30 min every 3 weeks is 5 mg/m(2), with a favorable toxicity profile of mild
      and infrequent diarrhea. Interpatient variability of pharmacokinetics was similar
      to or smaller than that with other camptothecin derivatives.

PMID- 11595696
TI  - Lack of correlation of functional scintigraphy with (99m)technetium
      methoxyisobutylisonitrile with histological necrosis following induction
      chemotherapy or measures of P-glycoprotein expression in high-grade osteosarcoma.
AB  - In osteosarcoma, some studies have suggested P-glycoprotein expression is a
      prognostic factor. The clearance of (99m)technetium hexakis-2
      methoxyisobutylisonitrile ((99m)Tc-MIBI) has been used in some tumor systems as
      an in vivo measure of P-glycoprotein-mediated efflux. In this study we explored
      the correlation between (99m)Tc-MIBI clearance and histological necrosis
      following induction chemotherapy and P-glycoprotein expression in osteosarcoma.
      The primary tumors of 20 patients with high-grade osteosarcoma were imaged at
      diagnosis with (99m)Tc-MIBI, and the uptake ratios and biological half-lives were
      calculated. P-Glycoprotein expression in the tumor tissue was determined
      immunohistochemically and by measuring mRNA expression of the multidrug
      resistance-1 gene. The histological necrosis following induction chemotherapy was
      assessed by the Huvos grading system. The biological half-life of (99m)Tc-MIBI
      ranged from 1.4 to 52.5 h. Seven of the 20 tumor samples had a favorable extent
      of necrosis following induction chemotherapy. The (99m)Tc-MIBI half-life and
      uptake ratio showed no correlation with histological necrosis following induction
      chemotherapy. The (99m)Tc-MIBI half-life and uptake ratio did not correlate with
      either measure of P-glycoprotein expression. The results of this pilot study
      indicate that (99m)Tc-MIBI imaging is not an effective predictor of histological
      necrosis following induction chemotherapy in high-grade osteosarcoma. (99m)Tc
      MIBI imaging did not correlate with measures of P-glycoprotein expression in the
      tumor tissue.

PMID- 11595697
TI  - Forearm blood flow and local responses to peptide vasodilators: a novel
      pharmacodynamic measure in the phase I trial of antagonist G, a neuropeptide
      growth factor antagonist.
AB  - PURPOSE: Arg-D-Trp-NmePhe-D-Trp-Leu-Met-NH(2) (Antagonist G), a substance P (SP 6
      11) analogue, inhibits mitogenesis stimulated by a broad spectrum of
      neuropeptides and has demonstrated antitumor activity in vitro and in vivo with
      IC(50) concentrations of 10-20 microM in small cell lung cancer and other cell
      lines. Because neuropeptides are part of complex neurohumoral pathways, we have
      sought to develop novel pharmacodynamic approaches as part of the early clinical
      development of this potential anticancer drug. EXPERIMENTAL DESIGN: A Phase I
      trial was performed in two stages. In stage 1, Antagonist G was administered at 3
      week intervals using an accelerated dose-escalation strategy until the target
      maximum plasma concentration (C(max)) of 10 microM was achieved. In stage 2, dose
      intensity was increased to weekly, and the inhibitory effect of i.v. Antagonist G
      was assessed by forearm blood flow (FBF) using SP as a vasodilator, as measured
      by venous plethysmography. RESULTS: In stage 1, dose was escalated from 2 to 300
      mg/m(2) in 12 dose levels using only 15 patients. In stage 2, nine patients were
      entered at three dose levels (300, 350, and 400 mg/m(2)) and a C(max) of 45
      microM was achieved. Facial flushing was the only consistent toxicity but was not
      dose limiting. FBF studies demonstrated that Antagonist G consistently inhibited
      the vasodilatory effects of SP (mean, 62 +/- 2% inhibition). CONCLUSIONS:
      Antagonist G can be safely administered up to 400 mg/m(2), achieving C(max)s >20
      microM by weekly 6-h i.v. infusion. FBF studies in patients demonstrated that
      Antagonist G inhibits SP vasodilatory effects in vivo at these doses in the
      absence of dose-limiting toxicity.

PMID- 11595698
TI  - Elevated expression of hTERT is associated with dysplastic cell transformation
      during human oral carcinogenesis in situ.
AB  - PURPOSE: Telomerase is a ribonucleoprotein complex composed of the catalytic
      protein subunit (human telomerase reverse transcriptase or hTERT) and the RNA
      template. This enzyme activity is a necessary and rate-limiting step of cellular
      immortalization and could provide a unique marker of aberrant cells, which may
      selectively be targeted. The current study was undertaken to quantitatively
      determine the degree of telomerase activation during multistage oral
      carcinogenesis using paraffin-embedded tissue samples. EXPERIMENTAL DESIGN: hTERT
      expression level was quantitatively compared between normal and cancerous oral
      tissues by real-time reverse-transcription-PCR (RT-PCR). Also, the presence of
      hTERT transcript in individual cells was surveyed in the biopsy specimens with
      varying degrees of histopathology by in situ RT-PCR. RESULTS: Low level of hTERT
      amplification was detected by real-time RT-PCR in most (11/13) normal human oral
      mucosa. hTERT expression was also detected in the majority (11/12) of squamous
      cell carcinoma tissues, and the level was significantly (P < 0.05) elevated, on
      the average, by a factor >6.9. By in situ RT-PCR, hTERT expression was not noted
      in normal epithelium (0/10) nor in mild dysplasia (0/7) but was detected in
      moderate dysplasia (4/5) and in those tissues with a higher grade of
      histopathology: severe dysplasia (3/3) and invasive carcinoma (4/4). CONCLUSIONS:
      These results indicate that enhanced expression of telomerase activity occurs
      early during human oral carcinogenesis and support the critical role of
      telomerase in the development of human oral cancer.

PMID- 11595699
TI  - Thioredoxin expression is associated with lymph node status and prognosis in
      early operable non-small cell lung cancer.
AB  - PURPOSE: Thioredoxin (TRX), a low molecular weight protein, exerts reduction
      oxidation control over a number of transcription factors involved in cell
      activation and proliferation. High TRX mRNA levels have been found in lung
      carcinomas, a trait associated with a growth and survival advantage. EXPERIMENTAL
      DESIGN: In this study, we examined the immunohistochemical expression of human
      TRX in normal lung and in 102 primary non-small cell lung carcinomas. RESULTS: In
      normal lung, the staining for TRX was cytoplasmic in the respiratory bronchial
      epithelium, alveolar epithelium, and alveolar macrophages. Bronchial glandular
      cells demonstrated a mixed nuclear and cytoplasmic staining. In lung carcinomas,
      the pattern of expression for TRX was predominantly cytoplasmic and only
      occasionally nuclear. A strong association between absence of TRX expression and
      regional lymph node negativity was observed (P = 0.004). High proliferation
      index, as detected with Ki-67 antibody, was associated with high TRX expression
      (P = 0.02). A significant correlation between high cytoplasmic p53 reactivity and
      low TRX expression was observed (P = 0.04). No association with grade, tumor
      stage, histology, or bcl-2 was noted. A significant coexpression of TRX with
      human activator protein endonuclease 1 was recorded (P = 0.04). Absence of TRX
      expression was associated with a better outcome (P < 0.05). CONCLUSIONS: We
      conclude that overexpression of TRX in non-small cell lung carcinomas is
      indicative of a more aggressive tumor phenotype and is associated with bad
      prognostic features and possibly with a poorer outcome.

PMID- 11595700
TI  - Allelic variants of aromatase and the androgen and estrogen receptors: toward a
      multigenic model of prostate cancer risk.
AB  - PURPOSE: The purpose of this study was to determine whether polymorphisms in the
      CAG repeat in exon 1 of the androgen receptor (AR), two intronic restriction
      sites in the estrogen receptor (ESR1 XbaI and ESR1 PvuII), and an Arg264Cy5
      substitution in the aromatase gene (CYP19) contribute to prostate cancer risk.
      EXPERIMENTAL DESIGN: A case-control study was performed with 88 Caucasian
      prostate cancer patients and 241 Caucasian male controls. Logistic regression
      models were used to assess individual and joint contributions of genotypes to
      prostate cancer risk. RESULTS: For single polymorphisms, only the AR repeat
      number was significantly related to increased prostate cancer risk [age- and body
      mass index (BMI)-adjusted odds ratio (OR), 1.14; 95% confidence interval (CI),
      1.04-1.25], suggesting a 14% increase in risk for each missing CAG repeat. When
      subjects were classified as either long (> or =23 AR CAG repeats) or short (<23
      repeats) carriers, a significant increase in risk was also observed (age- and BMI
      adjusted OR, 1.75; 95% CI, 1.05-2.95; P = 0.04). The aromatase C/T was associated
      with an increase in risk of borderline significance (age- and BMI-adjusted OR,
      2.50; 95% CI, 0.99-6.28). When examining the effects of two polymorphisms on
      prostate cancer risk, homozygosity for the ESR1 XbaI restriction site together
      with a longer AR was more frequent among controls (32%) than cases (18%; age- and
      BMI-adjusted OR, 0.39; 95% CI, 0.19-0.78). The aromatase C/C genotype together
      with a longer AR was also more frequent among controls (55%) than cases (41%; age
      and BMI-adjusted OR, 0.51; 95% CI, 0.30-0.89). CONCLUSIONS: Estrogen and
      aromatase may play a role in prostate cancer. A multigenic model of prostate
      cancer susceptibility is also supported.

PMID- 11595701
TI  - Cancer-associated myofibroblasts possess various factors to promote endometrial
      tumor progression.
AB  - Myofibroblastic invasion associated with malignant epithelial cells of
      endometrial cancer as well as other cancers is often found in the interstitium.
      To assess the myofibroblastic-epithelial interaction, frozen sections from a
      total of 10 endometrial cancers with or without invasive myofibroblasts were
      immunohistochemically examined. Interestingly, the invasive myofibroblasts
      adjacent to malignant epithelial cells showed frequently intensive positive
      staining of several growth factors such as vascular endothelial growth factor
      (VEGF), insulin-like growth factor I, and epidermal growth factor, the cognate
      receptors such as Fetal liver kinase-1/Kinase Insert Domain-containing
      receptor/VEGF receptor-2, fms-like tyrosine kinase-1/VEGF receptor-1, and
      epidermal growth factor receptor, several cell cycle regulators such as cyclins
      and cyclin dependent kinases, and estrogen receptor alpha. Moreover, we indicated
      that the majority of the myofibroblasts as well as cancer epithelial cells are
      proliferating because of their positive staining of proliferating cell nuclear
      antigen and Ki-67. Furthermore, the myofibroblasts were also positive of hypoxia
      inducible factor 1 alpha, which is a marker protein of hypoxia, probably followed
      by activation of VEGF-Flk-1 and VEGF-fms-like tyrosine kinase-1 signals, which
      could initiate angiogenesis. These findings suggest directly that the
      myofibroblasts might participate in the progression of tumor cells in terms of
      cancer cell growth stimulation and also activated initiation of angiogenesis.

PMID- 11595702
TI  - Reduced expression of focal adhesion kinase in liver metastases compared with
      matched primary human colorectal adenocarcinomas.
AB  - The focal adhesion kinase (FAK) is implicated in integrin-mediated signal
      transduction pathways used in cell adhesion, cell motility, apoptosis, and
      anchorage-independent growth. Because cancer invasion and metastasis are thought
      to be associated with alterations in cellular adhesive and motile properties, we
      studied the expression of four focal adhesion proteins including FAK in matched
      samples of human normal colorectal mucosa (N), primary colorectal adenocarcinomas
      (T) and liver metastases (M) from 10 patients by Western blot analysis. This gave
      us the advantage of directly comparing levels of focal adhesion protein
      expression within the same genetic background. Average FAK expression level was
      significantly higher in T than in N and it was significantly lower in M than in
      T. Average paxillin expression level was also significantly higher in T than in
      N, but it was not significantly different between T and M. Similar results were
      obtained by immunohistochemical analyses of FAK and paxillin expression. Average
      vinculin and talin expression levels showed no significant differences among
      these three samples (N, T, and M). These data demonstrate that the FAK expression
      level increases in primary tumors compared with normal mucosa and decreases in
      liver metastases to the level of normal mucosa in the majority of human
      colorectal adenocarcinomas. Up- and down-regulation of FAK protein expression
      observed in this study may have a profound effect on the signal transduction.

PMID- 11595703
TI  - Increased expression of matrix metalloproteinases 2 and 9 and tissue inhibitors
      of metalloproteinases 1 and 2 correlate with poor prognostic variables in renal
      cell carcinoma.
AB  - PURPOSE: Matrix metalloproteinases (MMPs) degrade components of the extracellular
      matrix and are implicated in tissue remodeling and tumor infiltration. Tissue
      inhibitor of metalloproteinases (TIMPs) inhibit enzymes of the MMP family and
      preserve stromal integrity, thus inhibiting tumor migration. Although numerous
      studies on several human carcinomas have demonstrated a role for MMPs in tumor
      metastasis and patient survival, their prognostic role in patients with renal
      cell carcinoma (RCC) has not been well defined. More importantly, the recently
      documented paradoxical functions of TIMPs have not been characterized in these
      neoplasms. EXPERIMENTAL DESIGN: Five-microm, formalin-fixed, paraffin-embedded
      tissue sections from 153 RCCs were immunostained using specific antibodies
      against MMP2, MMP9, (Novocastra, Burlingame, CA) TIMP1, and TIMP2 (NeoMarkers,
      Fremont, CA) proteins. Immunostaining was semiquantitatively scored based on
      intensity and distribution, and results were correlated with histological and
      prognostic variables. RESULTS: The rates of increased expression of MMPs and
      TIMPs in RCC were as follows: MMP2, 67%; MMP9, 43%; TIMP1, 46%; and TIMP2, 73%.
      Each of these four markers individually correlated with histological tumor type
      with a vast majority of papillary and sarcomatoid RCCs expressing these proteins
      as compared with clear cell tumors (P range, 0.0001-0.003). Significant
      coexpression of MMPs and TIMPs was observed (P = 0.0001). Increased
      immunoreactivity for each of these proteins correlated with high tumor grade (P
      range, 0.0001-0.01). On univariate analysis, expression of each of these markers
      correlated with shortened survival (P range, 0.004-0.05). On multivariate
      analysis, including tumor grade, stage, and all four markers, only advanced stage
      (P = 0.047) and increased TIMP1 expression (P = 0.007) independently predicted
      shortened survival. CONCLUSION: Increased expression of MMP2, MMP9, TIMP1, and
      TIMP2 proteins in RCCs correlate with poor prognostic variables including
      shortened patient survival. The paradoxical poor prognostic implication of TIMP
      overexpression complements the recently documented dual function of TIMPs and
      warrants further investigation.

PMID- 11595704
TI  - Prognostic significance of multidrug resistance protein in adult T-cell leukemia.
AB  - The response of adult T-cell leukemia (ATL) to chemotherapy is poor, and a major
      obstacle to successful treatment is intrinsic or acquired drug resistance. To
      determine the clinical significance of multidrug resistance protein (MRP) 1 in
      ATL, we studied MRP1 expression and its association with clinical outcome. The
      expression of MRP1 mRNA in leukemia cells from 48 ATL patients was studied by
      slot blot analysis. The expression level of MRP1 mRNA in chronic-type ATL was
      significantly higher than that in lymphoma-type ATL (P = 0.033). There was no
      correlation between MRP1 expression and age, gender, WBC count, LDH,
      hypercalcemia, blood urea nitrogen, or performance status. However, the
      expression of MRP1 mRNA correlated only with peripheral blood abnormal lymphocyte
      counts (P = 0.008). The transporting activity of MRP1 was assessed using membrane
      vesicles. Membrane vesicles prepared from ATL cells with high expression of MRP1
      mRNA showed a higher ATP-dependent leukotriene C(4) uptake than did those with
      low expression of MRP1 mRNA. This uptake was almost completely inhibited by
      LTD(4) antagonists ONO-1078 and MK571. In acute- and lymphoma-type ATL, high
      expression of MRP1 mRNA at diagnosis correlated with shorter survival, and Cox
      regression analysis revealed that MRP1 expression was an independent prognostic
      factor. These findings suggest that functionally active MRP1 is expressed in some
      ATL cells and that it is involved in drug resistance and has a possible causal
      relationship with poor prognosis in ATL. Multidrug resistance-reversing agents,
      such as ONO-1078 and MK571, that directly interact and inhibit the transporting
      activity of MRP1 may be useful for treating ATL patients.

PMID- 11595705
TI  - Cyclin D1 and p16 alterations in advanced premalignant lesions of the upper
      aerodigestive tract: role in response to chemoprevention and cancer development.
AB  - PURPOSE: To better understand the role of G(1)-S transition regulator
      abnormalities in the pathogenesis of advanced premalignant lesions of the upper
      aerodigestive tract and the biological effects of chemoprevention, we studied
      biopsies obtained sequentially from participants in a prospective trial using 13
      cis retinoic acid, IFN-alpha, and alpha-tocopherol for 12 months. EXPERIMENTAL
      DESIGN: Cyclin D1 and p16 expression were analyzed by immunohistochemistry, loss
      of heterozygosity by polymerase chain reacting amplification, and then
      electrophoretic separation of the products, methylation of the p16 promoter by
      methylation-specific polymerase chain reacting, and cyclin D1 gene amplification
      by fluorescence in situ hybridization. RESULTS: Baseline dysregulation of cyclin
      D1 expression was found in 50% (14 of 28) and was reversed in 6 of 14 cases,
      whereas p16 expression was lost in 46% (13 of 28) and regained in 2 of 13 cases.
      Loss of heterozygosity at 9p21 occurred in 68% and p16(INK4a) promoter
      methylation occurred in 75% of cases, with increasing frequency from mild to
      severe dysplasia. Cyclin D1 gene amplification was identified in two cases.
      Cyclin D1 protein dysregulation at last follow-up alone and in combination with
      p16 loss was associated with histological progression and cancer development (P <
      0.01). CONCLUSIONS: Additional study of these alterations in a larger sample and
      exploration of the upstream signaling partners of these cell cycle regulators in
      vivo is warranted to identify cancer risk profiles that would be meaningful
      targets for chemopreventive intervention.

PMID- 11595706
TI  - Molecular detection of p16 promoter methylation in the serum of patients with
      esophageal squamous cell carcinoma.
AB  - PURPOSE AND EXPERIMENTAL DESIGN: Recent evidence shows that the presence of
      promoter hypermethylation of tumor suppressor genes has been demonstrated in the
      serum DNA of patients with various cancers such as lung, liver, and head and neck
      cancer. We have examined promoter hypermethylation of the p16 gene in esophageal
      squamous cell carcinoma (SCC) using methylation-specific PCR to detect tumor DNA
      in the serum. RESULTS: Aberrant promoter methylation of the p16 gene was detected
      in 31 of 38 (82%) esophageal SCCs. Subsequently, we tested for promoter
      methylation in the paired serum DNA of 31 patients with a p16 alteration in the
      primary tumor. We found that 7 of these 31 (23%) patients had the same
      methylation changes in the serum DNA. CONCLUSIONS: This result indicates that
      promoter methylation present in the tumors of esophageal SCC patients can be
      detected in the serum of the same patient and that this approach can potentially
      be used for the screening and monitoring of the disease.

PMID- 11595707
TI  - Deletions on chromosome 8p22 may predict disease progression as well as
      pathological staging in prostate cancer.
AB  - PURPOSE: A recent report demonstrated that the deletion of chromosome 8p22 could
      predict disease progression in stage III (capsular penetrating) prostate cancer.
      We studied if the status of chromosomal deletions of 8p22 could reflect
      pathological stage as well as patient prognosis, thereby serving as a diagnostic
      tool to optimize the treatment strategy in prostate cancer. EXPERIMENTAL DESIGN:
      A total of 97 patients (41 Japanese and 56 Swedish) were studied by the
      fluorescence in situ hybridization technique. Seventy-seven patients (23 pT2, 18
      pT3, and 36 pN+ tumors) underwent surgery (radical prostatectomy or lymph node
      dissection). The specimens were prepared by touch biopsy. From another 20 cases,
      fine-needle aspiration biopsies were obtained. RESULTS: 8p22 deletions were
      detected in 47 (61%) and 11 (55%) specimens of 77 touch biopsies and 20 fine
      needle aspiration biopsies, respectively. No significant difference was found in
      the frequency of 8p22 deletion between different preparations of specimens, as
      well as between different races (Japanese versus Swedish). The frequency of 8p22
      deletion was statistically higher in patients with pT3 or more than in those with
      pT2 (P < 0.01). Disease progression was evaluated in 57 patients. The Cox
      proportional hazards model revealed 8p22 deletion to be the strongest parameter
      to predict disease progression (hazards ratio = 5.75; P = 0.0001). CONCLUSIONS:
      Studies on chromosomal deletions of 8p22 by fluorescence in situ hybridization
      technique may serve as a genetic marker to optimize the treatment strategy in
      patients with prostate cancer to the optimal treatment.

PMID- 11595708
TI  - Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian
      cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in
      Japanese population.
AB  - We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer
      families in Japan. The clinical characteristics of BRCA-associated ovarian cancer
      patients were compared with cases carrying no mutations as well as with
      population controls. Using a direct sequencing method, 45 of the 82 ovarian
      cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with
      BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent
      mutations were found and 2 of them, the L63X and Q934X mutations, were detected
      in seven and eight independent families, respectively. In addition, 16 mutations
      of BRCA1 and 3 mutations of BRCA2 have never been described previously. In
      consideration of clinicopathological features, there was a significantly higher
      proportion of tumors with serous adenocarcinoma and of cases of advanced stages
      in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand,
      there were no differences of mean age at diagnosis between patients with BRCA1 or
      BRCA2 mutation and those of the controls. Our results indicate that the features
      of BRCA-associated ovarian cancer in Japan appear to be similar to those in
      Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common
      founder mutations unique to the Japanese population.

PMID- 11595709
TI  - Nuclear expression of the Y-box binding protein, YB-1, as a novel marker of
      disease progression in non-small cell lung cancer.
AB  - Transcription factor Y-box binding protein 1 (YB-1) that binds to the inverted
      CCAAT box is involved not only in transcription of various genes but also in cell
      proliferation and DNA repair. We determined whether localization of YB-1 in
      either the nucleus or cytoplasm could serve as a prognostic marker for patients
      with non-small cell lung cancer (NSCLC). In 196 NSCLC patients, expression of YB
      1 protein in the nucleus or cytoplasm was immunohistochemically evaluated. Of the
      196 tumors examined, 88 (44.9%) were positive for YB-1 expression in the nucleus.
      Nuclear YB-1 expression significantly correlated with T factor, lymph node
      metastasis, and stage of the disease. Patients with a nuclear YB-1 tumor had a
      poorer prognosis than did those with a cytoplasmic YB-1 tumor in all of the NSCLC
      patients (P = 0.0494) and in patients with squamous cell carcinoma (P = 0.0313)
      but not in patients with adenocarcinomas. Nuclear localization of the YB-1
      protein may prove to be an important factor of disease progression for patients
      with NSCLC, in particular, in cases of squamous cell carcinoma.

PMID- 11595710
TI  - Novel antitumor effect of estradiol in athymic mice injected with a T47D breast
      cancer cell line overexpressing protein kinase Calpha.
AB  - PURPOSE: Resistance to tamoxifen (TAM) represents a significant challenge to the
      management of breast cancer. We previously reported that the estrogen receptor
      (ER)-negative hormone-independent T47D:C42 cell line has both elevated protein
      kinase Calpha (PKCalpha) protein expression and basal activator protein-1
      activity compared with the parental ER+ (hormone-dependent) T47D:A18 cell line.
      Stable transfection of PKCalpha to the T47D:A18 breast cancer cell line results
      in increased basal activator protein-1 activity, reduced ER function, increased
      proliferation rate, and hormone-independent growth (Tonetti et al., Br. J.
      Cancer, 83: 782-791, 2000). In this report, we further characterize the role of
      PKCalpha overexpression in vivo to elucidate a possible molecular mechanism of
      tamoxifen resistance. EXPERIMENTAL DESIGN: To determine whether the
      T47D:A18/PKCalpha cell line would produce hormone-independent tumors in athymic
      mice, we injected T47D:A18, T47D:A18/neo, or the T47D:A18/PKCalpha20 cell clones
      bilaterally into the mammary fat pads of athymic mice. Tumor growth was evaluated
      following treatment with estradiol (E2), TAM, and the pure antiestrogen, ICI
      182,780. RESULTS: Mice receiving either T47D:A18 or T47D:A18/neo cells produced
      tumors that grew in response to E2 treatment, whereas the untreated control and
      TAM-treated groups showed no tumor growth. Interestingly, mice receiving the
      T47D:A18/PKCalpha20 clone produced tumors in both the control and TAM groups,
      whereas tumor growth was inhibited in mice treated with E2. PKCalpha was also
      overexpressed in an MCF-7 tumor model that also exhibited TAM-stimulated and E2
      induced regression. CONCLUSIONS: These results suggest that overexpression of
      PKCalpha in breast tumors results in hormone-independent tumor growth that cannot
      be inhibited by TAM treatment. Furthermore, the finding that E2 has an antitumor
      effect on breast tumors overexpressing PKCalpha is a novel observation that may
      have important therapeutic implications.

PMID- 11595711
TI  - A new antiestrogen, 2-(4-hydroxy-phenyl)-3-methyl-1-[4-(2-piperidin-1-yl-ethoxy)
      benzyl]-1H-indol-5-ol hydrochloride (ERA-923), inhibits the growth of tamoxifen
      sensitive and -resistant tumors and is devoid of uterotropic effects in mice and
      rats.
AB  - PURPOSE: Tamoxifen is an antiestrogen used in women who have estrogen receptor
      (ER)-alpha-positive breast cancer. Unfortunately, resistance to tamoxifen is
      common in women with metastatic disease and side effects, including increased
      risk of endometrial cancer, exist. Here we describe the activity of a new
      selective ER modulator, ERA-923, in preclinical models focused on these
      limitations. EXPERIMENTAL DESIGN: The ability of ERA-923, 4-OH tamoxifen, or
      raloxifene to inhibit estrogen-stimulated growth was evaluated in cell-based and
      xenograft assays with tumor cells that are sensitive or resistant to tamoxifen.
      Uterine effects of selective ER modulators were compared in rodents. RESULTS: ERA
      923 potently inhibits estrogen binding to ER-alpha (IC(50), 14 nM). In ER-alpha
      positive human MCF-7 breast carcinoma cells, ERA-923 inhibits estrogen-stimulated
      growth (IC(50), 0.2 nM) associated with cytostasis. In vitro, a MCF-7 variant
      with inherent resistance to tamoxifen (10-fold) or 4-OH tamoxifen (>1000-fold)
      retains complete sensitivity to ERA-923. Partial sensitivity to ERA-923 exists in
      MCF-7 variants that have acquired profound tamoxifen resistance. In tumor-bearing
      animals, ERA-923 (10 mg/kg/day given p.o.) inhibits 17beta-estradiol-stimulated
      growth in human tumors derived from MCF-7, EnCa-101 endometrial, or BG-1 ovarian
      carcinoma cells, including a MCF-7-variant that is inherently resistant to
      tamoxifen. Raloxifene is inactive in the MCF-7 xenograft model. Unlike tamoxifen,
      droloxifene, or raloxifene, ERA-923 is not uterotropic in immature rats or
      ovariectomized mice. Consistent with this, tamoxifen, but not ERA-923, stimulates
      the growth of EnCa-101 tumors. CONCLUSIONS: In preclinical models, ERA-923 has an
      improved efficacy and safety compared with tamoxifen. Clinical trials with ERA
      923 are in progress.

PMID- 11595712
TI  - Chronotherapy and chronotoxicity of the cyclooxygenase-2 inhibitor, celecoxib, in
      athymic mice bearing human breast cancer xenografts.
AB  - PURPOSE: Inhibition of the enzyme cyclooxygenase with celecoxib is cytotoxic in a
      variety of solid tumor cell lines. Previous work has shown that by charting
      circadian rhythms, it has been possible to find optimal times to deliver a dose
      of drug, such that it is most efficacious in killing cancer cells and least
      harmful to normal tissues. Therefore, we examined the time dependence of toxicity
      (chronotoxicity) and of antitumor effects (chronotherapy) of celecoxib to
      determine optimal time of day for dosing with respect to light-dark cycles.
      EXPERIMENTAL DESIGN: Celecoxib was administered i.p. for 10 days (5 days on, 2
      days off, 5 days on) to nude mice bearing s.c. breast xenografts. Body weight,
      peripheral blood cells, clinical chemistry, and tumor growth were monitored.
      RESULTS: The highest tolerance (100% survival) was found at 7 HALO and the least
      occurred at 17 h after light onset (HALO; 10% survival). Chronotherapy at a 20
      mg/kg dose varied between the seven HALO evaluated and between the three breast
      tumors (MCF-7, ZR-75-30, and MDA-MB-468) studied. When the maximum tolerated dose
      (MTD) of celecoxib was optimized for each HALO, we found that at 7-10 HALO, the
      MTD was 25 mg/kg, whereas at 17-20 HALO; the MTD was only 10 mg/kg. Tumor
      regression was observed when dosing was done at 23 HALO to 7 HALO (5 a.m. to 1
      p.m.), whereas no therapeutic response was observed when dosing was done at 10-13
      HALO (4 p.m. to 7 p.m.), and rapid tumor growth was noted when dosing was done at
      17 HALO (11 p.m.). CONCLUSIONS: Tumor growth response to the MTD at each HALO
      revealed that there was no clear relationship between dose administered and
      therapeutic response. COX-2 expression was not able to explain either the
      chronotherapy or the chronotoxicity results obtained.

PMID- 11595713
TI  - Therapeutic advantage of (90)yttrium- versus (131)iodine-labeled PAM4 antibody in
      experimental pancreatic cancer.
AB  - OBJECTIVES: Radioimmunotherapy studies using (131)I-PAM4 have demonstrated
      significant antitumor effects in mice bearing human pancreatic cancer xenografts.
      For several reasons (90)Y has been proposed as a more effective radionuclide for
      radioimmunotherapy of pancreatic cancer. The present study examined whether one
      radionuclide was more efficacious than the other in tumor-bearing mice. METHODS:
      Athymic nude mice bearing CaPan1 xenograft tumors ( approximately 1.0 cm(3)) were
      given increasing doses of either (90)Y-PAM4 or (131)I-PAM4 up to their respective
      maximal tolerated doses [MTDs (260 and 700 microCi, respectively)]. RESULTS:
      (90)Y-PAM4 provided significantly greater growth inhibition than the (131)I-PAM4
      (P < 0.035). Median survival time for the untreated mice was 6 weeks, whereas
      median survival times for the (131)I-treated mice and (90)Y-treated mice at their
      respective MTDs were 17.5 weeks and >26 weeks (the end of the study period),
      respectively. Within the (131)I-PAM4-treated group, two of eight mice were
      responders (>50% decrease in tumor size) for a median of 14 weeks. At the end of
      the study (26 weeks), 1 mouse was alive with no sign of tumor. All of the (90)Y
      PAM4-treated mice were responders with a median duration of response of 20 weeks.
      Six of the seven mice were alive at week 26, with four mice having no evidence of
      disease. CONCLUSIONS: These data demonstrate the advantage of (90)Y over (131)I
      as the radionuclide for PAM4-targeted radioimmunotherapy of xenografted
      pancreatic cancer. Furthermore, the duration and extent of the antitumor response
      suggests that multiple treatment cycles of (90)Y-PAM4 may provide an effective
      therapeutic for the control of pancreatic cancer.

PMID- 11595714
TI  - In vitro prevention of the emergence of multidrug resistance in a pediatric
      rhabdomyosarcoma cell line.
AB  - We have established preclinical models for the development of drug resistance to
      vincristine (a major drug used in the treatment of pediatric rhabdomyosarcoma)
      using cell lines. The RD cell line has a mutant P53 phenotype and does not have
      detectable P-glycoprotein (P-gp) or multidrug resistance-related protein (MRP)
      despite expressing low levels of mdr-1 mRNA, which encodes P-gp and mrp1 mRNA.
      Resistant variants of RD were derived by exposure to increasing concentrations of
      vincristine. This was repeated on six occasions, resulting in three cell lines
      which could tolerate 64 x the IC(50) concentration. Six independent agents were
      tested for their ability to prevent the development of resistance in this model.
      Despite at least 10 attempts, resistance did not develop in the presence of the
      multidrug resistance (MDR) modulators PSC833, VX710, and XR9576. This strongly
      suggests that these agents may delay or even prevent the development of
      resistance to vincristine. This was also confirmed in a second rhabdomyosarcoma
      cell line, Rh30. In contrast, the agents indomethacin (MRP1 modulator), CGP41251
      (protein kinase C inhibitor), and dexrazoxane (putative MDR prevention agent) did
      not affect the development of resistance in the RD model. Characterization of the
      resistant cell lines indicated the presence of increased mdr-1 and P-gp
      expression, which resulted in resistance to the agents doxorubicin, etoposide,
      and vincristine but not cisplatin. The resistance could be modulated using PSC833
      or VX710, confirming that functional P-gp is present. No apparent differences
      were seen between the resistant cell lines derived in the absence and presence of
      the various agents. These experiments strongly suggest that the development of
      MDR may be preventable using modulators of MDR and merit clinical studies to test
      this hypothesis.

PMID- 11595716
TI  - Antiapoptotic activity is dispensable for insulin-like growth factor I receptor
      mediated clonogenic radioresistance after gamma-irradiation.
AB  - PURPOSE: The purpose of this study was to evaluate the relationship between
      apoptotic activity and clonogenic radiosensitivity in vitro using an insulin-like
      growth factor I receptor (IGF-IR) signaling model, which is known to exert
      tumorigenic and antiapoptotic effects. EXPERIMENTAL DESIGN: We used mouse embryo
      fibroblast cell lines expressing either human IGF-IR [R+(Wt) and R+] or the
      marker gene alone [R-(puro)]; these cell lines were derived from R- cells, which
      are deficient in IGF-IR. After gamma-irradiation, apoptotic activity was
      determined by the presence of DNA fragmentation and caspase-3-, -8-, and -9-like
      activities. Clonogenic radiosensitivity was determined by a colony-forming assay.
      RESULTS: R+(Wt) and R+ cells expressed similar levels of IGF-IR, transducing
      phosphorylation signals to major downstream substrates on insulin-like growth
      factor I stimulation. R+ cells were resistant to the induction of apoptosis after
      gamma-irradiation; however, both R+(Wt) and R-(puro) cells demonstrated
      significant DNA fragmentation and increase in caspase-3-, -8-, and -9-like
      activities. Both R+(Wt) and R+ cells were radioresistant (to a similar extent)
      compared with R-(puro) cells as measured by a colony-forming assay. Clonogenic
      radioresistance was not influenced by the inhibition of Akt/protein kinase B
      through treatment with wortmannin at low concentrations specifically inhibiting
      phosphatidylinositol 3'-kinase. CONCLUSIONS: Our findings indicate that apoptotic
      activity does not necessarily predict clonogenic survival after exposure to
      ionizing radiation. This study provides clinical implications in the evaluation
      of apoptotic activities observed during the course of radiotherapy to predict
      accurate tumor response or local control.

PMID- 11595715
TI  - Experimental therapeutics with a new 10-deazaaminopterin in human mesothelioma:
      further improving efficacy through structural design, pharmacologic modulation at
      the level of MRP ATPases, and combined therapy with platinums.
AB  - Studies described here sought to evaluate the therapeutic potential of a new 10
      deazaaminopterin analogue, 10-propargyl-10-deazaaminopterin (PDX), alone and in
      combination with platinum compounds in the treatment of human pleural
      mesothelioma. In vitro studies documented 25-30-fold and 3-fold, respectively,
      greater cytotoxic potency of PDX compared with methotrexate and another 10
      deazaaminopterin, edatrexate, against VAMT-1 and JMN cell lines derived from
      human mesothelioma. These tumor cell lines were also inhibited by platinum
      compounds. Cisplatin (CDDP) was somewhat more inhibitory than oxaloplatin and >1
      log order in magnitude more inhibitory than carboplatin (CBCDA). Against the JMN
      tumor xenografted in nude mice, whereas methotrexate and, more so, edatrexate,
      were potently growth inhibitory, only PDX brought about substantial regression.
      By comparison, CDDP and CBCDA, but not oxaloplatin were markedly growth
      inhibitory to this same tumor in vivo. This high level of therapeutic activity of
      PDX could be additionally enhanced by coadministration of probenecid, an
      inhibitor of canicular multispecific organic anion transporter/multidrug
      resistance-related protein (MRP)-like ATPases, which increased the number of
      complete regressions by >-3 fold. Canicular multispecific organic anion
      transporter/MRP genes, primarily 1, 3, 4, 5, and 7, were in fact expressed in
      these human mesothelioma cell lines as determined by real-time reverse
      transcription-PCR. These same MRP genes, including, to a lesser extent, MRP-4,
      were also expressed in pleural mesotheliomas derived from patients as shown by
      the same methodology. When combined with CDDP or CBCDA, PDX achieved 2-fold
      greater overall regression of the JMN tumor with a 3-4-fold increase in complete
      regressions, although some attenuation of dosages of each were required in the
      combination. These results strongly suggest that PDX has significant potential in
      the treatment of human pleural mesothelioma, particularly when coadministered
      with probenecid or combined with platinum compounds.

PMID- 11595717
TI  - Motexafin gadolinium: a redox active drug that enhances the efficacy of bleomycin
      and doxorubicin.
AB  - The effect of motexafin gadolinium (MGd), a redox mediator, on tumor response to
      doxorubicin (Dox) and bleomycin (Bleo) was investigated in vitro and in vivo. MES
      SA human uterine sarcoma cells were studied in vitro using a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay. Rif-1, a
      murine fibrosarcoma cell line, was studied using a clonogenic survival assay.
      Tumor growth delay assays were performed using the EMT-6 murine mammary sarcoma
      cell line in BALB/c mice. MGd (25-100 microM) produced dose-dependent enhancement
      of Bleo cytotoxicity to MES-SA cells. The IC(50) for Bleo was reduced by
      approximately 10-fold using 100 microM MGd. In clonogenic assays using Rif-1
      cells, MGd enhanced the activity of Bleo approximately 1000-fold. This effect was
      shown to be mediated, in part, by MGd inhibition of potentially lethal damage
      repair. MGd enhanced the tumor response to bleomycin and Dox in vivo. MGd had no
      significant effect on the systemic exposure to Dox (expressed in terms of the
      plasma area under the curve, 0-24 h) and did not increase Dox myelosuppression.
      MGd enhanced the effectiveness of the redox active drugs, Bleo and Dox.

PMID- 11595718
TI  - Schedule-dependent activity of topotecan in OVCAR-3 ovarian carcinoma xenograft:
      pharmacokinetic and pharmacodynamic evaluation.
AB  - Topotecan is a topoisomerase (Topo) I inhibitor used in ovarian carcinoma
      chemotherapy. Topo I inhibitors are thought to be more cytotoxic using protracted
      schedules of administration. We tested this hypothesis on a preclinical model:
      human ovarian carcinoma OVCAR-3 implanted i.p. Nude mice were treated i.p. with a
      total dose of topotecan of 12.5 mg/kg delivered in 1, 5, 10, 20, 40, or 80 daily
      injections. The toxicity was maximal when the total dose was delivered within 5
      and 10 days of treatment. However, the efficacy was the greatest (all of the mice
      cured) in the 20-day schedule using 0.625 mg/kg/day, hence, making this latter
      schedule the most efficient without any major toxicity. A pharmacokinetic study
      was conducted to identify parameters related to the efficacy and toxicity of
      topotecan in our model. The use of a population pharmacokinetic approach allowed
      us to define a therapeutic window: maintaining plasma concentrations above 0.2
      microM for >10 h was necessary for an optimal antitumor effect and avoiding
      plasma concentrations >0.7 microM allowed a manageable toxicity. Finally, Topo I
      activity was monitored in ascites from animals treated with different topotecan
      administration schedules. The optimal schedule defined above allowed for
      sustained inhibition of Topo I activity associated with a greater antitumor
      activity. These in vivo data constitute a rationale for clinical studies testing
      this type of administration.

PMID- 11595720
TI  - Expression of Her-2/neu in human lung cancer cell lines by immunohistochemistry
      and fluorescence in situ hybridization and its relationship to in vitro
      cytotoxicity by trastuzumab and chemotherapeutic agents.
AB  - Overexpression of the Her-2/neu oncogene and receptor protein was reported in
      approximately 20% of breast cancers and was associated with a poor prognosis. Her
      2/neu expression was a predictor for response to trastuzumab, a monoclonal
      antibody that recognizes the Her-2/neu cell surface receptor. Data regarding the
      expression of Her-2/neu in lung cancer are far more limited, and there is little
      information regarding the influence of Her-2/neu expression and response to
      trastuzumab alone or in combination with chemotherapeutic agents. In this report
      we evaluated Her-2/neu gene expression by fluorescence in situ hybridization
      (FISH) and the cell surface expression of the Her-2/neu receptor by
      immunohistochemistry using the HercepTest and by FACS analysis in 31 lung cancer
      cell lines with 5 breast cancer cell lines as controls. By FACS, we found Her
      2/neu overexpression (mean fluorescence intensity >8) in 2 of the 22 non-small
      cell lung cancer (NSCLC) cell lines (9%), none of 11 small cell lung cancer
      (SCLC) cell lines, and 4 of 5 breast cancer cell lines. A positive HercepTest (2+
      or 3+) was found in 6 of 19 NSCLC cell lines (26%, 2+; 5%, 3+), 1 of 3 SCLC cell
      lines (33%), and 4 of 5 breast cancer cell lines (80%). One of 6 NSCLC cell lines
      examined (17%) had gene amplification with >32 copies of Her-2/neu/cell and had
      homogeneous staining regions. One NSCLC cell line had a maximum of 14 copies of
      Her-2/neu/cell, and 3 had modest increases in Her-2/neu gene copy number without
      gene amplification (maximum 5-8 copies/cell). None of the SCLC cell lines had
      more than a maximum of 4 copies/cell, whereas the 2 breast cancer cell lines had
      maximum Her-2/neu copy numbers of 80 and 5, respectively. Aneusomy rather than
      true amplification was the major cause of increased Her-2/neu expression in most
      of the NSCLC cell lines. There was a strong correlation when the results of
      fluorescence-activated cell sorter, HercepTest results, and FISH were compared in
      pairs. Furthermore, Trastuzumab produced a G(1) cell cycle arrest and growth
      inhibition only in cell lines expressing Her-2/neu. The IC(50) for growth
      inhibition was correlated with cell surface Her-2/neu expression. The combination
      of trastuzumab and chemotherapeutic agents produced more than additive growth
      inhibition in cell lines expressing Her-2/neu, but the level of additivity was
      not related to the amount of Her-2/neu expression. These data indicate that
      trastuzumab alone and in combination with chemotherapeutic agents should be
      tested in NSCLC patients and that Her-2/neu should be assessed by both
      immunohistochemistry and FISH methods in these studies to determine which test is
      the best predictor of outcome.

PMID- 11595719
TI  - Tumor targeting by covalent conjugation of a natural fatty acid to paclitaxel.
AB  - Certain natural fatty acids are taken up avidly by tumors for use as biochemical
      precursors and energy sources. We tested in mice the hypothesis that the
      conjugation of docosahexaenoic acid (DHA), a natural fatty acid, and an
      anticancer drug would create a new chemical entity that would target tumors and
      reduce toxicity to normal tissues. We synthesized DHA-paclitaxel, a 2'-O-acyl
      conjugate of the natural fatty acid DHA and paclitaxel. The data show that the
      conjugate possesses increased antitumor activity in mice when compared with
      paclitaxel. For example, paclitaxel at its optimum dose (20 mg/kg) caused neither
      complete nor partial regressions in any of 10 mice in a Madison 109 (M109) s.c.
      lung tumor model, whereas DHA-paclitaxel caused complete regressions that were
      sustained for 60 days in 4 of 10 mice at 60 mg/kg, 9 of 10 mice at 90 mg/kg, and
      10 of 10 mice at the optimum dose of 120 mg/kg. The drug seems to be inactive as
      a cytotoxic agent until metabolized by cells to an active form. The conjugate is
      less toxic than paclitaxel, so that 4.4-fold higher molar doses can be delivered
      to mice. DHA-paclitaxel in rats has a 74-fold lower volume of distribution and a
      94-fold lower clearance rate than paclitaxel, suggesting that the drug is
      primarily confined to the plasma compartment. DHA-paclitaxel is stable in plasma,
      and high concentrations are maintained in mouse plasma for long times. Tumor
      targeting of the conjugate was demonstrated by pharmacokinetic studies in M109
      tumor-bearing mice, indicating an area under the drug concentration-time curve of
      DHA-paclitaxel in tumors that is 8-fold higher than paclitaxel at equimolar doses
      and 57-fold higher at equitoxic doses. At equimolar doses, the tumor area under
      the drug concentration-time curve of paclitaxel derived from i.v. DHA-paclitaxel
      is 6-fold higher than for paclitaxel derived from i.v. paclitaxel. Even at 2
      weeks after treatment, 700 nM paclitaxel remains in the tumors after DHA
      paclitaxel treatment. Low concentrations of DHA-paclitaxel or paclitaxel derived
      from DHA-paclitaxel accumulate in gastrocnemius muscle; which may be related to
      the finding that paclitaxel at 20 mg/kg caused hind limb paralysis in nude mice,
      whereas DHA-paclitaxel caused none, even at doses of 90 or 120 mg/kg. The dose
      limiting toxicity in rats is myelosuppression, and, as in the mouse, little DHA
      paclitaxel is converted to paclitaxel in plasma. Because DHA-paclitaxel remains
      in tumors for long times at high concentrations and is slowly converted to
      cytotoxic paclitaxel, DHA-paclitaxel may kill those slowly cycling or residual
      tumor cells that eventually come into cycle.

PMID- 11595721
TI  - Sequence-dependent enhancement of cytotoxicity produced by ecteinascidin 743 (ET
      743) with doxorubicin or paclitaxel in soft tissue sarcoma cells.
AB  - Ecteinascidin 743 (ET-743) is a potent antitumor agent from the Caribbean
      tunicate Ecteinascidin turbinata and is presently in clinical trials for human
      cancers. To better understand how ET-743 might be used clinically, the present
      study used SRB assays to examine the cytotoxicity resulting from combining ET-743
      with three other antineoplastic agents: doxorubicin (DXR), trimetrexate, and
      paclitaxel in different administration schedules in two soft tissue sarcoma cell
      lines, HT-1080 and HS-18, in vitro. Concurrent exposure of ET-743 with DXR
      resulted in synergistic interactions in both cell lines. Addition of ET-743 for
      24 h before DXR was the most effective cytotoxic regimen against both cell lines.
      Morphological study by fluorescence microscopy revealed that combination
      treatment of both cells with ET-743 and DXR induced apoptosis. Exposure to
      paclitaxel before ET-743 was also an effective regimen. These results encourage
      studies of the combination of ET-743 and DXR in the treatment of soft tissue
      sarcoma, because each of these agents have activity in this disease.

PMID- 11595722
TI  - Paclitaxel liposome aerosol treatment induces inhibition of pulmonary metastases
      in murine renal carcinoma model.
AB  - The present studies were undertaken to evaluate the pulmonary pharmacokinetics
      and therapeutic efficacy of paclitaxel (PTX) administered by aerosol. PTX was
      encapsulated into dilauroylphosphatidylcholine liposomal formulations (PTX-DLPC).
      The deposition and clearance of PTX-DLPC in the lungs administered by aerosol or
      i.v. at comparative doses was performed, and PTX was quantitatively determined in
      tissue extracts by high-performance liquid chromatography analysis. The murine
      renal carcinoma (Renca) pulmonary metastases model was used to determine the
      therapeutic effect of drug formulation administered by aerosol. PTX-DLPC aerosols
      were generated with the Aero-Mist jet nebulizer (cis-USA). The most effective
      schedule of treatment was when mice inhaled the drug for 30 min 3 days per week.
      There was a significant reduction of the lung weights and reduced number of
      visible tumor foci on the lung surfaces of mice treated with PTX aerosol (P <
      0.004 and P < 0.01, respectively) compared with control groups. Inhalation of PTX
      DLPC also led to prolonged survival in mice inoculated with Renca cells. The
      results of the present studies demonstrate the therapeutic potential of aerosol
      technology for lung cancer treatment.

PMID- 11595723
TI  - Tumor uptake and elimination of 2',2'-difluoro-2'-deoxycytidine (gemcitabine)
      after deoxycytidine kinase gene transfer: correlation with in vivo tumor
      response.
AB  - PURPOSE: We hypothesized that tumor uptake and elimination of 2',2'-difluoro-2'
      deoxycytidine/2',2'-difluoro-2'-deoxycytidine 5'-triphosphate (dFdCyd/dFdCTP)
      would be altered after dCK gene transfer and that this change would result in an
      enhanced cytotoxic effect. To test this hypothesis, we examined dFdCyd/dFdCTP
      uptake and clearance in HT-29 human colon carcinoma xenografts in nude mice by
      high-performance liquid chromatography (HPLC) and fluorine-19 magnetic resonance
      spectroscopy (F-19 MRS). EXPERIMENTAL DESIGN: HT-29 tumors were grown from cells
      infected with either the retroviral vector alone (LNPO-LacZ) or vector containing
      the dCK gene (LNPO-dCK). HPLC and F-19 MRS analyses were performed after a single
      160 mg/kg i.p. injection of dFdCyd. Tumor response was determined in animals
      receiving a similar dosing schedule of dFdCyd. RESULTS: HPLC experiments revealed
      an increased tumor accumulation of dFdCTP in xenografts overexpressing dCK
      compared with wild-type controls (P < or = 0.05). dFdCTP in the dCK-infected
      tumors was easily identified at 24 h postinjection. Conversely, no dFdCTP could
      be detected in the control xenografts 14 h postinjection. Subsequent F-19 MRS
      experiments confirmed an altered uptake, revealing a 2.5-fold greater
      accumulation of dFdCyd/dFdCTP in the dCK xenografts. Whereas a modest tumor
      growth delay was observed in the wild-type tumors receiving dFdCyd, dCK
      xenografts demonstrated a marked tumor growth delay following treatment (P < or =
      0.05). CONCLUSIONS: These data support the hypothesis that increased expression
      of dCK cDNA in HT-29 xenografts results in an enhanced dFdCTP accumulation and
      prolonged elimination kinetics, and ultimately a potentiated in vivo tumor
      response to dFdCyd. Related to these effects, changes in the overall tumor
      metabolism of dFdCyd/dFdCTP was detectable by noninvasive F-19 MRS. These data
      are relevant to future preclinical and clinical studies evaluating dCK gene
      transfer and dFdCyd therapy.

PMID- 11595724
TI  - Wortmannin inhibits pkb/akt phosphorylation and promotes gemcitabine antitumor
      activity in orthotopic human pancreatic cancer xenografts in immunodeficient
      mice.
AB  - Pancreatic cancer is resistant to almost all classes of cytotoxic agents.
      Gemcitabine seems to be the current drug of choice. We have recently reported
      that inhibition of the phosphatidylinositide 3-kinase-protein kinase B (PKB/Akt)
      cell survival pathway by wortmannin enhances gemcitabine-induced apoptosis in
      cultured human pancreatic cancer cells (1). The present study investigated the
      effects of wortmannin on orthotopic human pancreatic cancer xenografts implanted
      in severe combined immunodeficient mice. Animals were given single i.v. bolus
      injections of 0.175, 0.35, or 0.7 mg/kg of wortmannin and killed at 0.5, 1, 2, or
      4 h after treatment. Phosphorylated PKB/Akt levels in tumor tissues were measured
      by fluorescence image analysis. Wortmannin was found to inhibit PKB/Akt
      phosphorylation in a time- and dose-dependent manner, reaching a plateau at 4 h
      and at 0.7 mg/kg. The levels of phosphorylated PKB/Akt were maximally decreased
      by approximately 50% relative to the vehicle control. Subsequently, the extent of
      apoptosis in tumors treated with gemcitabine or wortmannin alone or in
      combination was determined using terminal deoxynucleotidyl transferase-mediated
      nick end labeling assay and computerized image analysis. Orthotopic tumors
      exposed to 80 mg/kg gemcitabine for 48 h and then 0.7 mg/kg wortmannin for 4 h
      showed a 5-fold increase (P = 0.002) in apoptosis compared with those treated
      with each agent alone and with the vehicle control. The combination treatment
      also significantly (P < 0.001) inhibited tumor growth. Taken together, our
      findings support the potential of phosphatidylinositide 3-kinase inhibitors as
      adjuncts to conventional chemotherapy in the treatment of pancreatic cancer.

PMID- 11595725
TI  - The T cell death knell: immune-mediated tumor death in renal cell carcinoma.
AB  - The antitumor effect of T cells is executed either through CD95 or Perforin
      (PFN)/Granzyme B (GrB) pathways. Induction of apoptosis by either mode requires
      activation of caspase family members. However, recent studies have suggested that
      cell death can proceed in the absence of caspase induction and apoptotic events.
      We investigated the contribution of CD95 and PFN/GrB-mediated cytotoxicity to
      apoptotic and necrotic mechanisms of cell death in human renal cell carcinoma.
      Although freshly isolated and cultured tumors expressed CD95 on their surface,
      they were resistant to CD95-mediated apoptosis. CD95 resistance coincided with
      decreased levels of FADD protein and diminished caspase-3-like activity. In
      contrast, we demonstrated that tumor cell death mediated by PFN/GrB can be
      achieved in the absence of functional caspase activity and is accompanied by a
      dramatic accumulation of nonapoptotic necrotic cells.

PMID- 11595726
TI  - Functional impairment of melanoma-associated p16(INK4a) mutants in melanoma cells
      despite retention of cyclin-dependent kinase 4 binding.
AB  - PURPOSE: Melanoma-associated germ-line mutations affecting the tumor suppressor
      and cyclin-dependent kinase (CDK) inhibitor, CDKN2A/p16(INK4a) have been
      identified in >100 melanoma-prone families. To predict the melanoma risk for
      carriers of specific mutations, it is useful to test the function of the mutant
      proteins in biochemical assays; however, it is unclear how well these results
      correlate with their cellular effects. We examined the relationship between loss
      of CDK binding by mutant proteins and various measures of cellular growth in
      melanoma cells. EXPERIMENTAL DESIGN: The cellular activities of four melanoma
      associated p16(INK4a) mutations (Arg24Pro, Ala36Pro, Met53Ile, and Val126Asp)
      were compared by use of inducible expression in stably transfected melanoma
      cells, deficient in expression of the endogenous protein, and compared with their
      ability to bind CDK4. RESULTS: The cell cycle-inhibitory activity of all of the
      mutants was profoundly reduced, and partially retained capacity for CDK4 binding
      in functional assays did not correlate with significant preservation of cell
      cycle-regulatory function. CONCLUSION: Testing of p16(INK4a) interactions with
      CDKs in protein-binding assays is an unreliable predictor of mutant p16(INK4a)
      function in cells. In addition to exhibiting reduced stability, these mutant
      proteins may also be defective in interaction with cellular targets other than
      CDKs.

PMID- 11595727
TI  - Matrilysin mediates extracellular cleavage of E-cadherin from prostate cancer
      cells: a key mechanism in hepatocyte growth factor/scatter factor-induced cell
      cell dissociation and in vitro invasion.
AB  - PURPOSE: The current study examined the effects of hepatocyte growth
      factor/scatter factor (HGF/SF) on cell-cell dissociation, invasion, and its
      association with the mediated release of matrix metalloproteinase-7 (Matrilysin)
      on the extracellular cleavage of E-cadherin in prostate cancer cells.
      EXPERIMENTAL DESIGN: The effects of HGF/SF on cell-cell dissociation, in vitro
      invasion, and on the expression of E-cadherin at both protein and mRNA levels
      were assessed in cells whose expression of Matrilysin was altered by treatment
      with antisense oligonucleotide. RESULTS: Incubation with HGF/SF mediated the
      release of active Matrilysin (M(r) 19,000), resulting in extracellular cleavage
      of E-cadherin from prostate cancer cells. This resultant soluble M(r) 80,000
      fragment of E-cadherin was subsequently recognized upon immunoprobing with an
      anti-E-cadherin antibody. Both recombinant human Matrilysin (rh-Matrilysin)
      and/or HGF/SF increased the level of soluble E-cadherin and decreased the level
      of full-length (M(r) 120,000) E-cadherin as detected by Western blotting. The
      effects of rh-Matrilysin and HGF/SF were inhibited by an antisense
      oligonucleotide specifically directed toward human Matrilysin. In addition,
      stimulation with either rh-Matrilysin or HGF/SF resulted in disruption to the E
      cadherin/beta-catenin complex, as shown by a significant increase (P < 0.05) in
      both cell scattering and invasion index. CONCLUSIONS: Treatment with HGF/SF
      induced Matrilysin-mediated cleavage to the extracellular domain of E-cadherin,
      resulting in its dissociation from the cadherin/catenin complex. This provides a
      new mechanism in HGF/SF-induced cell scattering, resulting in a switch to a more
      invasive phenotype in LNCapFGC cells, as demonstrated by in vitro invasion.

PMID- 11595728
TI  - Expression of interleukin 8 and its receptors in human colon carcinoma cells with
      different metastatic potentials.
AB  - PURPOSE: In the present study, we examined the expression of a multifunctional
      cytokine, interleukin 8 (IL-8), and its receptors, CXCR1 and CXCR2, in human
      colon carcinoma cells with different metastatic potentials and determined their
      role in modulating phenotypes associated with metastasis. EXPERIMENTAL DESIGN: IL
      8, CXCR1, and CXCR2 protein and mRNA expression were examined using ELISA,
      immunocytochemistry, and reverse transcription-PCR in human colon carcinoma cells
      with different metastatic potentials. IL-8-mediated proliferation, migration, and
      tumor-endothelial cell interaction were analyzed. RESULTS: IL-8 mRNA and protein
      expression was very low in Caco2 cells but elevated in KM12C cells and very high
      in KM12L4 cells, suggesting an association between the IL-8 production and
      metastatic potential. Similarly, CXCR1 and CXCR2 expression was lower in Caco2
      cells than in low and high metastatic KM12C and KM12L4 cells. The recombinant
      human IL-8 enhanced the proliferation of colon carcinoma cells. Furthermore,
      proliferation of low and high metastatic cells expressing different levels of IL
      8 was inhibited by neutralizing antibodies to IL-8, CXCR1, and CXCR2. We observed
      significant differences in the invasive potential of colon carcinoma cells
      expressing different levels of IL-8. In addition, we observed that IL-8 modulates
      adhesion of tumor cells to endothelial cells in an autocrine and paracrine
      manner. CONCLUSION: Our present data suggest an association between constitutive
      expression of IL-8 and aggressiveness in human colon carcinoma cells and the
      possible role of IL-8 in modulating different metastatic phenotypes associated
      with progression and metastasis.

PMID- 11595729
TI  - Correspondence re: E. Sabo et al., Microscopic Analysis and Significance of
      Vascular Architectural Complexity in Renal Cell Carcinoma. Clin. Cancer Res., 7:
      533-537, 2001.

PMID- 11595732
TI  - Retinoic acid-mediated growth arrest requires ubiquitylation and degradation of
      the F-box protein Skp2.
AB  - The mechanism by which all-trans retinoic acid (ATRA) leads to a G(1) arrest of
      the cell cycle remains unclear. We show here that the decrease in D-type cyclin
      levels observed following ATRA treatment correlates with an increase in the rate
      of cyclin D1 ubiquitylation in both T-47D and MCF-7 breast cancer cell lines.
      However, MCF-7 cells are more resistant to ATRA than T-47D cells indicating that
      cyclin D1 degradation is not sufficient for ATRA-mediated arrest. We found a
      striking difference between these cells in that while ATRA induces an elevation
      in the cdk inhibitor p27 in T-47D cells, this is not observed in the ATRA
      resistant MCF-7 cells. Furthermore, we demonstrate that ATRA promotes the
      ubiquitylation of Skp2, an F-box protein that targets p27 for degradation.
      Moreover, overexpression of Skp2 in T-47D cells prevents accumulation of p27 and
      promotes resistance to ATRA. In addition, overexpression of cyclin D1 in T-47D
      cells also promotes ATRA resistance. We found that the mechanism of ATRA-induced
      ubiquitylation of cyclin D1 and Skp2 is independent of CUL-1 expression and that
      ATRA can rescue cyclin D1 degradation in the uterine cell line SK-UT-1, where D
      type cyclins are stabilized due to a specific defect in proteolysis. These data
      suggest that ATRA induces a novel pathway of ubiquitylation and that the
      degradation of the F-box protein Skp2 is the mechanism underlying p27
      accumulation and cyclin E-cdk2 inactivation following ATRA treatment.

PMID- 11595731
TI  - Substrate water exchange in photosystem II depends on the peripheral proteins.
AB  - The (18)O exchange rates for the substrate water bound in the S(3) state were
      determined in different photosystem II sample types using time-resolved mass
      spectrometry. The samples included thylakoid membranes, salt-washed Triton X-100
      prepared membrane fragments, and purified core complexes from spinach and
      cyanobacteria. For each sample type, two kinetically distinct isotopic exchange
      rates could be resolved, indicating that the biphasic exchange behavior for the
      substrate water is inherent to the O(2)-evolving catalytic site in the S(3)
      state. However, the fast phase of exchange became somewhat slower (by a factor of
      approximately 2) in NaCl-washed membrane fragments and core complexes from
      spinach in which the 16- and 23-kDa extrinsic proteins have been removed,
      compared with the corresponding rate for the intact samples. For CaCl(2)-washed
      membrane fragments in which the 33-kDa manganese stabilizing protein (MSP) has
      also been removed, the fast phase of exchange slowed down even further (by a
      factor of approximately 3). Interestingly, the slow phase of exchange was little
      affected in the samples from spinach. For core complexes prepared from
      Synechocystis PCC 6803 and Synechococcus elongatus, the fast and slow exchange
      rates were variously affected. Nevertheless, within the experimental error,
      nearly the same exchange rates were measured for thylakoid samples made from wild
      type and an MSP-lacking mutant of Synechocystis PCC 6803. This result could
      indicate that the MSP has a slightly different function in eukaryotic organisms
      compared with prokaryotic organisms. In all samples, however, the differences in
      the exchange rates are relatively small. Such small differences are unlikely to
      arise from major changes in the metal-ligand structure at the catalytic site.
      Rather, the observed differences may reflect subtle long range effects in which
      the exchange reaction coordinates become slightly altered. We discuss the results
      in terms of solvent penetration into photosystem II and the regional dielectric
      around the catalytic site.

PMID- 11595733
TI  - Induction of endothelial nitric-oxide synthase phosphorylation by the raloxifene
      analog LY117018 is differentially mediated by Akt and extracellular signal
      regulated protein kinase in vascular endothelial cells.
AB  - Raloxifene is a tissue-selective estrogen receptor modulator. The effect of
      estrogen on cardiovascular disease is mainly dependent on direct actions on the
      vascular wall involving activation of endothelial nitric oxide synthase (eNOS)
      via Akt and extracellular signal-regulated protein kinase (ERK) cascades.
      Although raloxifene is also known to activate eNOS in the vascular endothelium,
      the molecular mechanism responsible for this effect remains to be elucidated. In
      studies of both human umbilical vein endothelial cells and simian virus 40
      transformed rat lung vascular endothelial cells (TRLECs), the raloxifene analog
      LY117018 caused acute phosphorylation of eNOS that was unaffected by actinomycin
      D and was blocked by the pure estrogen receptor antagonist ICI182,780. Activation
      of Akt by raloxifene reached a plateau at 15-30 min and declined thereafter, a
      similar time frame to that of Akt activation by 17beta-estradiol. On the other
      hand, both activation and phosphorylation of ERK by raloxifene showed a biphasic
      pattern (peaks at 5 min and 1 h), whereas ERK activation and phosphorylation by
      17beta-estradiol reached a plateau at 5 min and declined thereafter. A MEK
      inhibitor, PD98059, had no effect on the raloxifene-induced Akt activity,
      suggesting an absence of cross-talk between the ERK and Akt cascades. Either
      exogenous expression of a dominant-negative Akt or pretreatment of TRLECs with
      PD98059 decreased the raloxifene-induced eNOS phosphorylation. Moreover,
      raloxifene stimulated the activation of Akt, ERK, and eNOS in Chinese hamster
      ovary cells expressing estrogen receptor alpha but not Chinese hamster ovary
      cells expressing estrogen receptor beta. Our findings suggest that raloxifene
      induced eNOS phosphorylation is mediated by estrogen receptor alpha via a
      nongenomic mechanism and is differentially mediated by Akt- and ERK-dependent
      cascades.

PMID- 11595734
TI  - DNA array studies demonstrate convergent regulation of virulence factors by Cph1,
      Cph2, and Efg1 in Candida albicans.
AB  - Candida albicans, normally a human commensal, can cause fatal systemic infections
      under certain circumstances. Its unique ability to switch from yeast to hyphal
      growth in response to various environmental signals is inherent to its
      pathogenicity. Filamentation is regulated by multiple pathways including a Cph1
      mediated mitogen-activated protein kinase pathway, an Efg1-mediated cAMP/PKA
      pathway, and a Cph2 pathway. To gain a general picture of how these various
      signaling pathways regulate differential gene expression during filamentation, we
      have constructed a partial C. albicans DNA array of 7,000 genes and used it to
      study the gene expression profiles using various mutants and growth conditions.
      By combining this novel technology with a new liquid medium in which cph1/cph1 is
      defective in filamentation, previously identified differentially expressed genes
      (ECE1, HWP1, HYR1, RBT1, SAPs5-6, and RBT4) are found to be regulated by all
      three pathways. In addition, two novel genes, DDR48 and YPL184, have been found
      to be differentially regulated during hyphal development and by all three
      pathways. This suggests that distinct filamentation signaling pathways converge
      to regulate a common set of differentially expressed genes. As one of the
      mechanisms for the observed convergence, we find that the transcription of a key
      regulator, TEC1, is regulated by Efg1 and Cph2. Importantly, most of the genes
      regulated by multiple filamentation pathways encode known virulence factors.
      Perhaps, C. albicans utilizes converging pathways to regulate its vital virulence
      factors to ensure its survival and pathogenicity in various host environments.

PMID- 11595735
TI  - Polypurine tract formation by Ty1 RNase H.
AB  - To better understand the mechanism by which Ty1 RNase H creates the polypurine
      tract (PPT) primer, we have demonstrated the polymerase-dependent hydrolytic
      activity of Ty1 reverse transcriptase (RT) during minus-strand synthesis. Using
      RNase H and polymerase mutants of the recombinant Ty1 RT protein, we show that
      the two domains of Ty1 RT can act independently of one another. Our results
      indicate that RNA/DNA substrates containing a short RNA PPT, which serve as
      primers for plus-strand DNA synthesis, are relatively resistant to RNase H
      cleavage. RNA substrates with a correct 5' end but with 3' end extending beyond
      the plus-strand initiation site were cleaved specifically to generate the correct
      3' end of the PPT. Using long RNA/DNA duplexes containing the PPT, we show that
      Ty1 RT is able to make specific internal cleavages that could generate the plus
      strand primer with correct 5' and 3' ends. Long RNA/DNA duplexes with mutations
      in the PPT or in a U-rich region upstream of the PPT, which abolish plus-strand
      initiation in vivo, were not cleaved specifically at the 5' end of the PPT. Our
      work demonstrates that the in vitro enzyme can recapitulate key processes that
      control proper replication in vivo.

PMID- 11595736
TI  - Thapsigargin and dimethyl sulfoxide activate medium P(i)<-->HOH oxygen exchange
      catalyzed by sarcoplasmic reticulum Ca2+-ATPase.
AB  - Thapsigargin is a potent inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase. It
      binds the Ca(2+)-free E2 conformation in the picomolar range, supposedly
      resulting in a largely catalytically inactive species. We now find that
      thapsigargin has little effect on medium P(i) <--> HOH oxygen exchange and that
      this activity is greatly stimulated (up to 30-fold) in the presence of 30% (v/v)
      Me(2)SO. Assuming a simple two-step mechanism, we have evaluated the effect of
      thapsigargin and Me(2)SO on the four rate constants governing the reaction of
      P(i) with Ca(2+)-ATPase. The principal effect of thapsigargin alone is to
      stimulate EP hydrolysis (k(-2)), whereas that of Me(2)SO is to greatly retard
      P(i) dissociation (k(-1)), accounting for its well known effect on increasing the
      apparent affinity for P(i). These effects persist when the agents are used in
      combination and substantially account for the activated oxygen exchange
      (v(exchange) = k(-2)[EP]). Kinetic simulations show that the overall rate
      constant for the formation of EP is very fast (approximately 300 s(-1)) when the
      exchange is maximal. Thapsigargin greatly stabilizes Ca(2+)-ATPase against
      denaturation in detergent in the absence of Ca(2+), as revealed by glutaraldehyde
      cross-linking, suggesting that the membrane helices lock together. It seems that
      the reactions at the phosphorylation site, associated with the activated exchange
      reaction, are occurring without much movement of the transport site helices, and
      we suggest that they may be associated solely with an occluded H+ state.

PMID- 11595737
TI  - In vivo regulation of oxidative phosphorylation in cells harboring a stop-codon
      mutation in mitochondrial DNA-encoded cytochrome c oxidase subunit I.
AB  - The mechanisms that regulate oxidative phosphorylation in mammalian cells are
      largely unknown. To address this issue, cybrids were generated by fusing
      osteosarcoma cells devoid of mitochondrial DNA (mtDNA) with platelets from a
      patient with a stop-codon mutation in cytochrome c oxidase subunit I (COX I). The
      molecular and biochemical characteristics of cybrids harboring varying levels of
      mutated mitochondrial DNA were studied. We found a direct correlation between the
      levels of mutated COX I DNA and mutated COX I mRNA, whereas the levels of COX I
      total mRNA were unchanged. COX I polypeptide synthesis and steady-state levels
      were inversely proportional to mutation levels. Cytochrome c oxidase subunit II
      was reduced proportionally to COX I, indicating impairment in complex assembly.
      COX enzymatic activity was inversely proportional to the levels of mutated mtDNA.
      However, both cell respiration and ATP synthesis were preserved in cells with
      lower proportions of mutated genomes, with a threshold at approximately 40%, and
      decreased linearly with increasing mutated mtDNA. These results indicate that COX
      levels in mutated cells were not regulated at the transcriptional, translational,
      and post-translational levels. Because of a small excess of COX capacity, the
      levels of expression of COX subunits exerted a relatively tight control on
      oxidative phosphorylation.

PMID- 11595738
TI  - Complex of transfer-messenger RNA and elongation factor Tu. Unexpected modes of
      interaction.
AB  - Transfer-messenger RNA (tmRNA) is a stable RNA in bacteria of 360 +/- 40
      nucleotides that can be charged with alanine and can function as both tRNA and
      mRNA. Ribosomes that are stalled either in a coding region of mRNA or at the 3'
      end of an mRNA fragment lacking a stop codon are rescued by replacing their mRNA
      for tmRNA. Here we demonstrate that the interaction of tmRNA with the elongation
      factor Tu shows unexpected features. Deacylated tmRNA can form a complex with
      either EF-Tu.GDP or EF-Tu.GTP, the association constants are about one order of
      magnitude smaller than that of an Ala-tRNA.EF-Tu.GTP complex. tmRNA as well as
      Ala-tmRNA can be efficiently cross-linked with EF-Tu.GDP using a zero-length
      cross-link. The efficiency of cross-linking in the case of deacylated tmRNA does
      not depend on an intact CCA-3' end and is about the same, regardless whether
      protein mixtures such as the post-ribosomal supernatant (S100 enzymes) or
      purified EF-Tu are present. Two cross-linking sites with EF-Tu.GDP have been
      identified that are located outside the tRNA part of tmRNA, indicating an unusual
      interaction of tmRNA with EF-Tu.GDP.

PMID- 11595739
TI  - Mediation of proliferating cell nuclear antigen (PCNA)-dependent DNA replication
      through a conserved p21(Cip1)-like PCNA-binding motif present in the third
      subunit of human DNA polymerase delta.
AB  - The subunit that mediates binding of proliferating cell nuclear antigen (PCNA) to
      human DNA polymerase delta has not been clearly defined. We show that the third
      subunit of human DNA polymerase delta, p66, interacts with PCNA through a
      canonical PCNA-binding sequence located in its C terminus. Conversely, p66
      interacts with the domain-interconnecting loop of PCNA, a region previously shown
      to be important for DNA polymerase delta activity and for binding of the cell
      cycle inhibitor p21(Cip1). In accordance with this, a peptide containing the PCNA
      binding domain of p21(Cip1) inhibited p66 binding to PCNA and the activity of
      native three-subunit DNA polymerase delta. Furthermore, pull-down assays showed
      that DNA polymerase delta requires p66 for interaction with PCNA. More
      importantly, only reconstituted three-subunit DNA polymerase delta displayed PCNA
      dependent DNA replication that could be inhibited by the PCNA-binding domain of
      p21(Cip1). Direct participation of p66 in PCNA-dependent DNA replication in vivo
      is demonstrated by co-localization of p66 with PCNA and DNA polymerase delta
      within DNA replication foci. Finally, in vitro phosphorylation of p66 by cyclin
      dependent kinases suggests that p66 activity may be subject to cell cycle
      dependent regulation. These results suggest that p66 is the chief mediator of
      PCNA-dependent DNA synthesis by DNA polymerase delta.

PMID- 11595740
TI  - Sarco/endoplasmic reticulum calcium ATPase-2 expression is regulated by ATF6
      during the endoplasmic reticulum stress response: intracellular signaling of
      calcium stress in a cardiac myocyte model system.
AB  - The recently described transcription factor, ATF6, mediates the expression of
      proteins that compensate for potentially stressful changes in the endoplasmic
      reticulum (ER), such as reduced ER calcium. In cardiac myocytes the maintenance
      of optimal calcium levels in the sarcoplasmic reticulum (SR), a specialized form
      of the ER, is required for proper contractility. The present study investigated
      the hypothesis that ATF6 serves as a regulator of the expression of
      sarco/endoplasmic reticulum calcium ATPase-2 (SERCA2), a protein that transports
      calcium into the SR from the cytoplasm. Depletion of SR calcium in cultured
      cardiac myocytes fostered the translocation of ATF6 from the ER to the nucleus,
      activated the promoter for rat SERCA2, and led to increased levels of SERCA2
      protein. SERCA2 promoter induction by calcium depletion was partially blocked by
      dominant-negative ATF6, whereas constitutively activated ATF6 led to SERCA2
      promoter activation. Mutation analyses identified a promoter-proximal ER stress
      response element in the rat SERCA2 gene that was required for maximal induction
      by ATF6 and calcium depletion. Although this element was shown to be responsible
      for all of the effects of ATF6 on SERCA2 promoter activation, it was responsible
      for only a portion of the effects of calcium depletion. Thus, SERCA2 induction in
      response to calcium depletion appears to be a potentially physiologically
      important compensatory response to this stress that involves intracellular
      signaling pathways that are both dependent and independent of ATF6.

PMID- 11595741
TI  - Cdc42 interacts with the exocyst and regulates polarized secretion.
AB  - Polarized delivery and incorporation of proteins and lipids to specific domains
      of the plasma membrane is fundamental to a wide range of biological processes
      such as neuronal synaptogenesis and epithelial cell polarization. The exocyst
      complex is specifically localized to sites of active exocytosis and plays
      essential roles in secretory vesicle targeting and docking at the plasma
      membrane. Sec3p, a component of the exocyst, is thought to be a spatial landmark
      for polarized exocytosis. In a search for proteins that regulate the localization
      of the exocyst in the budding yeast Saccharomyces cerevisiae, we found that
      certain cdc42 mutants affect the polarized localization of the exocyst proteins.
      In addition, we found that these mutant cells have a randomized protein secretion
      pattern on the cell surface. Biochemical experiments indicated that Sec3p
      directly interacts with Cdc42 in its GTP-bound form. Genetic studies demonstrated
      synthetically lethal interactions between cdc42 and several exocyst mutants.
      These results have revealed a role for Cdc42 in exocytosis. We propose that Cdc42
      coordinates the vesicle docking machinery and the actin cytoskeleton for
      polarized secretion.

PMID- 11595742
TI  - Low molecular weight protein-tyrosine phosphatase is involved in growth
      inhibition during cell differentiation.
AB  - Low molecular weight protein-tyrosine phosphatase (LMW-PTP) is an enzyme involved
      in mitogenic signaling and cytoskeletal rearrangement after platelet-derived
      growth factor (PDGF) stimulation. Recently, we demonstrated that LMW-PTP is
      regulated by a redox mechanism involving the two cysteine residues of the
      catalytic site, which turn reversibly from reduced to oxidized state after PDGF
      stimulation. Since recent findings showed a decrease of intracellular reactive
      oxygen species in contact inhibited cells and a lower tyrosine phosphorylation
      level in dense cultures in comparison to sparse ones, we studied if the level of
      endogenous LMW-PTP is regulated by growth inhibition conditions, such as cell
      confluence and differentiation. Results show that both cell confluence and cell
      differentiation up-regulate LMW-PTP expression in C2C12 and PC12 cells. We
      demonstrate that during myogenesis LMW-PTP is regulated at translational level
      and that the protein accumulates at the plasma membrane. Furthermore, we showed
      that both myogenesis and cell-cell contact lead to a dramatic decrease of
      tyrosine phosphorylation level of PDGF receptor. In addition, we observed an
      increased association of the receptor with LMW-PTP during myogenesis. Herein, we
      demonstrate that myogenesis decreases the intracellular level of reactive oxygen
      species, as observed in dense cultures. As a consequence, LMW-PTP turns from
      oxidized to reduced form during muscle differentiation, increasing its activity
      in growth inhibition conditions such as differentiation. These data suggest that
      LMW-PTP plays a crucial role in physiological processes, which require cell
      growth arrest such as confluence and differentiation.

PMID- 11595743
TI  - Analysis of integral membrane protein contributions to the deformability and
      stability of the human erythrocyte membrane.
AB  - Three major hypotheses have been proposed to explain the role of membrane
      spanning proteins in establishing/maintaining membrane stability. These
      hypotheses ascribe the essential contribution of integral membrane proteins to
      (i) their ability to anchor the membrane skeleton to the lipid bilayer, (ii)
      their capacity to bind and stabilize membrane lipids, and (iii) their ability to
      influence and regulate local membrane curvature. In an effort to test these
      hypotheses in greater detail, we have modified both the membrane skeletal and
      lipid binding interactions of band 3 (the major membrane-spanning and skeletal
      binding protein of the human erythrocyte membrane) and have examined the impact
      of these modifications on erythrocyte membrane morphology, deformability, and
      stability. The desired changes in membrane skeletal and protein-lipid
      interactions were induced by 1) reaction of the cells with 4,4'
      diisothiocyanostilbene-2,2'-disulfonate (DIDS), an inhibitor of band 3-mediated
      anion transport that dissociates band 3 into dimers (increasing its surface area
      in contact with lipid) and severs band 3 linkages to the membrane skeleton; 2) a
      fragment of ankyrin that ruptures the same ankyrin-band 3 bridge to the membrane
      skeleton, but drives the band 3 subunit equilibrium toward the tetramer (i.e.
      decreasing the band 3 surface area in contact with lipid); and 3) an antibody to
      the ankyrin-binding site on band 3 that promotes the same changes in band 3
      skeletal and lipid interactions as the ankyrin fragment. We observed that
      although DIDS induced echinocytic morphological changes in the treated
      erythrocytes, it had little impact on either membrane deformability or stability.
      In contrast, resealing of either the ankyrin fragment or anti-band 3 IgG into
      erythrocytes caused spontaneous membrane fragmentation and loss of
      deformability/stability. Because these and other new observations cannot all be
      reconciled with any single hypothesis on membrane stability, we suggest that more
      than one hypothesis may be operative and provide an explanation of how each might
      individually contribute to net membrane stability.

PMID- 11595744
TI  - The N-terminal regions of estrogen receptor alpha and beta are unstructured in
      vitro and show different TBP binding properties.
AB  - The N-terminal regions of the estrogen receptor alpha (ER alpha-N) and beta (ER
      beta-N) were expressed and purified to homogeneity. Using NMR and circular
      dichroism spectroscopy, we conclude that both ER alpha-N and ER beta-N are
      unstructured in solution. The TATA box-binding protein (TBP) has been shown
      previously to interact with ER alpha-N in vitro and to potentiate ER-activated
      transcription. We used surface plasmon resonance and circular dichroism
      spectroscopy to confirm and further characterize the ER-N-TBP interaction. Our
      results show that the intrinsically unstructured ER alpha-N interacts with TBP,
      and suggest that structural changes are induced in ER alpha-N upon TBP
      interaction. Conformational changes upon target factor interaction have not
      previously been demonstrated for any N-terminal region of nuclear receptors. In
      addition, no binding of ER beta-N to TBP was detected. This difference in TBP
      binding could imply differential recruitment of target proteins by ER alpha-N and
      ER beta-N. The affinity of the ER alpha-N-TBP interaction was determined to be in
      the micromolar range (K(D) = 10(-6) to 10(-5) m). Our results support models of
      TBP as a target protein for the N-terminal activation domain of ER alpha.
      Further, our results suggest that target proteins can induce and/or stabilize
      ordered structure in N-terminal regions of nuclear receptors upon interaction.

PMID- 11595745
TI  - HIV-1 preintegration complexes preferentially integrate into longer target DNA
      molecules in solution as detected by a sensitive, polymerase chain reaction-based
      integration assay.
AB  - After entering a cell and undergoing reverse transcription, the retroviral genome
      is contained in a preintegration complex (PIC) that mediates its integration into
      host cell DNA. PICs have been shown to prefer torsionally strained DNA, but the
      effect of target DNA length has not been previously examined. In this report,
      concatemerization of a repeating 105-base pair unit was used to vary target DNA
      length independently from basic DNA sequence, while maintaining both PICs and
      target DNAs in solution. Integration junctions were quantified by real-time
      fluorescence-monitored polymerase chain reaction amplification using primers in
      the viral long terminal repeat and the target DNA. Unreacted target DNA severely
      inhibited the post-reaction polymerase chain reaction detection step, requiring
      its removal using lambda exonuclease digestion. Integration into a 32-unit
      concatemer of target DNA was markedly more efficient than integration into a
      monomeric unit, indicating that longer target DNA was preferred. This substrate
      was used to construct a simple, robust, and adaptable assay that can serve as a
      method for studying the host cell factors that enhance PIC integration, and as a
      drug discovery platform for integration inhibitors active against PICs.

PMID- 11595746
TI  - Three-dimensional structure of transporter associated with antigen processing
      (TAP) obtained by single Particle image analysis.
AB  - The transporter associated with antigen processing (TAP) is an ATP binding
      cassette transporter responsible for peptide translocation into the lumen of the
      endoplasmic reticulum for assembly with major histocompatibility complex class I
      molecules. Immunoaffinity-purified TAP particles comprising TAP1 and TAP2
      polypeptides, and TAP2 particles alone were characterized after detergent
      solubilization and studied by electron microscopy. Projection structures of
      TAP1+2 particles reveal a molecule approximately 10 nm across with a deeply
      staining central region, whereas TAP2 molecules are smaller in projection. A
      three-dimensional structure of TAP reveals it is isolated as a single
      heterodimeric complex, with the TAP1 and TAP2 subunits combining to create a
      central 3-nm-diameter pocket on the predicted endoplasmic reticulum-lumenal side.
      Its structural similarity to other ABC transporters demonstrates a common
      tertiary structure for this diverse family of membrane proteins.

PMID- 11595747
TI  - Evidence that the transmembrane domain proximal region of the human T-cell
      leukemia virus type 1 fusion glycoprotein gp21 has distinct roles in the
      prefusion and fusion-activated states.
AB  - To investigate the structural context of the fusion peptide region in human T
      cell leukemia virus type 1 gp21, maltose-binding protein (MBP) was used as an N
      terminal solubilization partner for the entire gp21 ectodomain (residues 313-445)
      and C-terminally truncated ectodomain fragments. The bacterial expression of the
      MBP/gp21 chimeras resulted in soluble trimers containing intramonomer disulfide
      bonds. Detergents blocked the proteolytic cleavage of fusion peptide residues in
      the MBP/gp21-(313-425) chimera, indicating that the fusion peptide is available
      for interaction with detergent despite the presence of an N-terminal MBP domain.
      Limited proteolysis experiments indicated that the transmembrane domain proximal
      sequence Thr(425)-Ala(439) protects fusion peptide residues from chymotrypsin.
      MBP/gp21 chimera stability therefore depends on a functional interaction between
      N-terminal and transmembrane domain proximal regions in a gp21 helical hairpin
      structure. In addition, thermal aggregation experiments indicated that the
      Thr(425)-Ser(436) sequence confers stability to the fusion peptide-containing
      MBP/gp21 chimeras. The functional role of the transmembrane domain proximal
      sequence was assessed by alanine-scanning mutagenesis of the full-length envelope
      glycoprotein, with 11 of 12 single alanine substitutions resulting in 1.5- to 4.5
      fold enhancements in cell-cell fusion activity. By contrast, single alanine
      substitutions in MBP/gp21 did not significantly alter chimera stability,
      indicating that multiple residues within the transmembrane domain proximal region
      and the fusion peptide and adjacent glycine-rich segment contribute to stability,
      thereby mitigating the potential effects of the substitutions. The fusion
      enhancing effects of the substitutions are therefore likely to be caused by
      alteration of the prefusion complex. Our observations suggest that the function
      of the transmembrane domain proximal sequence in the prefusion envelope
      glycoprotein is distinct from its role in stabilizing the fusion peptide region
      in the fusion-activated helical hairpin conformation of gp21.

PMID- 11595748
TI  - Zn(2+) induces permeability transition pore opening and release of pro-apoptotic
      peptides from neuronal mitochondria.
AB  - Rapid entry of Ca(2+) or Zn(2+) kills neurons. Mitochondria are major sites of
      Ca(2+)-dependent toxicity. This study examines Zn(2+)-initiated mitochondrial
      cell death signaling. 10 nm Zn(2+) induced acute swelling of isolated
      mitochondria, which was much greater than that induced by higher Ca(2+) levels.
      Zn(2+) entry into mitochondria was dependent upon the Ca(2+) uniporter, and the
      consequent swelling resulted from opening of the mitochondrial permeability
      transition pore. Confocal imaging of intact neurons revealed entry of Zn(2+)
      (with Ca(2+)) to cause pronounced mitochondrial swelling, which was far greater
      than that induced by Ca(2+) entry alone. Further experiments compared the
      abilities of Zn(2+) and Ca(2+) to induce mitochondrial release of cytochrome c
      (Cyt-c) or apoptosis-inducing factor. In isolated mitochondria, 10 nm Zn(2+)
      exposures induced Cyt-c release. Induction of Zn(2+) entry into cortical neurons
      resulted in distinct increases in cytosolic Cyt-c immunolabeling and in cytosolic
      and nuclear apoptosis-inducing factor labeling within 60 min. In comparison,
      higher absolute [Ca(2+)](i) rises were less effective in inducing release of
      these factors. Addition of the mitochondrial permeability transition pore
      inhibitors cyclosporin A and bongkrekic acid decreased Zn(2+)-dependent release
      of the factors and attenuated neuronal cell death as assessed by trypan blue
      staining 5-6 h after the exposures.

PMID- 11595749
TI  - Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide
      exchange factors.
AB  - Signaling specificity of Rho GTPase pathways is achieved in part by selective
      interaction between members of the Dbl family guanine nucleotide exchange factors
      (GEFs) and their Rho GTPase substrates. For example, Trio, GEF-H1, and Tiam1 are
      a subset of GEFs that specifically activate Rac1 but not the closely related
      Cdc42. The Rac1 specificity of these GEFs appears to be governed by Rac1-GEF
      binding interaction. To understand the detailed mechanism underlying the GEF
      specificity issue, we have analyzed a panel of chimeras made between Rac1 and
      Cdc42 and examined a series of point mutants of Rac1 made at the switch I, switch
      II, and beta(2)/beta(3) regions for their ability to interact with and to be
      activated by the GEFs. The results reveal that Rac1 residues of both the switch I
      and switch II regions are involved in GEF docking and GEF-mediated nucleotide
      disruption, because mutation of Asp(38), Asn(39), Gln(61), Tyr(64), or
      Arg(66)/Leu(67) into Ala results in the loss of GEF binding, whereas mutation at
      Tyr(32), Asp(65), or Leu(70)/Ser(71) leads to the loss of GEF catalysis while
      retaining the binding capability. The region between amino acids 53-72 of Rac1 is
      required for specific recognition and activation by the GEFs, and Trp(56) in
      beta(3) appears to be the critical determinant. Introduction of Trp(56) to Cdc42
      renders it fully responsive to the Rac-specific GEF in vitro and in cells.
      Further, a polypeptide derived from the beta(3) region of Rac1 including the
      Trp(56) residue serves as a specific inhibitor for Rac1 interaction with the
      GEFs. Taken together, these results indicate that Trp(56) is the necessary and
      sufficient determinant of Rac1 for discrimination by the subset of Rac1-specific
      GEFs and suggest that a compound mimicking Trp(56) action could be explored as an
      interfering reagent specifically targeting Rac1 activation.

PMID- 11595750
TI  - Carcinoembryonic antigen cell adhesion molecule 1 directly associates with
      cytoskeleton proteins actin and tropomyosin.
AB  - CEA cell adhesion molecule 1 (CEACAM1), a type 1 transmembrane and homotypic cell
      adhesion protein belonging to the carcinoembryonic antigen (CEA) gene family and
      expressed on epithelial cells, is alternatively spliced to produce four major
      isoforms with three or four Ig-like ectodomains and either long (CEACAM1-L) or
      short (CEACAM1-S) cytoplasmic domains. When murine MC38 (methylcholanthrene
      induced adenocarcinoma 38) cells were transfected with human CEACAM1-L and
      stimulated with sodium pervanadate, actin was found to co-localize with CEACAM1-L
      at cell-cell boundaries but not in untreated cells. When CEACAM1-L was
      immunoprecipitated from pervanadate-treated MC38/CEACAM1-L cells and the
      associated proteins were analyzed by two-dimensional gel analysis and mass
      spectrometry, actin and tropomyosin, among other proteins, were identified.
      Whereas a glutathione S-transferase (GST) fusion protein containing the l-isoform
      (GST-Cyto-L) bound poorly to F-actin in a co-sedimentation assay, the S-isoform
      fusion protein (GST-Cyto-S) co-sedimented with F-actin, especially when incubated
      with G-actin during polymerization (K(D) = 7.0 microm). Both GST-Cyto-S and GST
      Cyto-L fusion proteins bind G-actin and tropomyosin by surface plasmon resonance
      studies with binding constants of 0.7 x 10(-8) and 1.0 x 10(-7) m for GST-Cyto-L
      to G-actin and tropomyosin, respectively, and 3.1 x 10(-8) and 1.3 x 10(-7) m for
      GST-Cyto-S to G-actin and tropomyosin, respectively. Calmodulin or EDTA inhibited
      binding of the GST-Cyto-L fusion protein to G-actin, whereas calmodulin and G
      actin, but not EDTA, stimulated binding to tropomyosin. A biotinylated 14-amino
      acid peptide derived from the juxtamembrane portion of the cytoplasmic domain of
      CEACAM1-L associated with both G-actin and tropomyosin with K(D) values of 1.3 x
      10(-5) and 1.8 x 10(-5) m, respectively. These studies demonstrate the direct
      interaction of CEACAM1 isoforms with G-actin and tropomyosin and the direct
      interaction of CEACAM1-S with F-actin.

PMID- 11595751
TI  - Exploitation of the HIV-1 coat glycoprotein, gp120, in neurodegenerative studies
      in vivo.
AB  - Neuronal loss has often been described at post-mortem in the brain neocortex of
      patients suffering from AIDS. Neuroinvasive strains of HIV infect macrophages,
      microglial cells and multinucleated giant cells, but not neurones. Processing of
      the virus by cells of the myelomonocytic lineage yields viral products that, in
      conjunction with potentially neurotoxic molecules generated by the host, might
      initiate a complex network of events which lead neurones to death. In particular,
      the HIV-1 coat glycoprotein, gp120, has been proposed as a likely aetiologic
      agent of the described neuronal loss because it causes death of neurones in
      culture. More recently, it has been shown that brain neocortical cell death is
      caused in rat by intracerebroventricular injection of a recombinant gp120 coat
      protein, and that this occurs via apoptosis. The latter observation broadens our
      knowledge in the pathophysiology of the reported neuronal cell loss and opens a
      new lane of experimental research for the development of novel therapeutic
      strategies to limit damage to the brain of patients suffering from HIV-associated
      dementia.

PMID- 11595752
TI  - A novel untranslated 'exon H' of the human choline acetyltransferase gene in
      placenta.
AB  - To investigate the existence of 5'-region(s) of human choline acetyltransferase
      (hChAT) mRNA in placenta we analyzed the presence or absence of ChAT 5'
      untranslated regions (UTR) in human neuronal and non-neuronal cells. Total RNA
      from human spinal cord, placenta, cultured choriocarcinoma JEG-3 and
      neuroblastoma CHP126 and MC-IXC cells was reverse transcribed and used for
      polymerase chain reaction amplification (RT-PCR). We used a sense primer located
      in the 5'-flanking region, in the previously defined intronic sequence and an
      anti-sense primer located in the common coding exon 2 of the hChAT gene. An
      amplified product of 567 bp in size was obtained only in human placenta and in
      JEG-3 cells whereas it was absent in spinal cord, CHP126 and MC-IXC cells. It was
      designated 'H-type' of ChAT mRNA. Whereas CHP126 produced the R- and N-type of
      ChAT mRNAs, no transcript of the N-and R-type was detected in JEG-3 and human
      placenta. In addition, CHP126 and JEG-3 cells and placenta showed the expression
      of the M-type of ChAT mRNA. The identity of the amplified 567 bp product (H-type)
      was confirmed by Southern hybridization and sequencing. The nucleotide sequence
      of the amplified fragment in placenta revealed the existence of a previously
      unknown type of ChAT mRNA produced by alternative splicing. Using primer
      extension we further determined the transcription initiation site of the H-type
      hChAT mRNA in placenta. These results demonstrate the expression of a novel ChAT
      mRNA isoform in human placenta in addition to the M-type. These data may be
      possibly explained by the presence of a placenta specific promoter in the ChAT
      gene, which might be the proximal promoter P1.

PMID- 11595753
TI  - Expression of glucose transporter GLUT3 by endotoxin in cultured rat astrocytes:
      the role of nitric oxide.
AB  - The induction of nitric oxide (NO) synthase in astrocytes by endotoxin and/or
      cytokine treatment is associated with increased glucose consumption and
      glycolysis, but the mechanism whereby this phenomenon occurs remains obscure. In
      this work, we have addressed this issue and found that incubation of cultured rat
      astrocytes with lipopolysaccharide (LPS; 1 microg/mL) for 24 h increased the
      level of constitutively expressed GLUT1 glucose transporter mRNA, and triggered
      GLUT3 mRNA expression, which was absent in normal astrocytes. The occurrence of
      GLUT3 protein after LPS treatment was corroborated by western blotting and
      immunocytochemistry. A 4-h incubation of astrocytes in the absence of glucose, or
      under an oxygen-poor (3%) atmosphere also resulted in GLUT3 mRNA overexpression.
      Experiments performed with 2-deoxy-D-[U-14C]glucose (at 0.1 mM of D-glucose)
      confirmed that LPS (0.1-10 microg/mL) dose-dependently increased the rate of
      glucose uptake (by a factor of 1.6 at 1 microg/mL of LPS), which was paralleled
      with the increase in NO synthesis. Furthermore, blockade of NO synthase with 2
      amino-5,6-dihydro-6-methyl-(4H)-1,3-thiazine (AMT; 50 microM) partially (by 45%)
      prevented the LPS-mediated increase in glucose uptake. Finally, incubation of
      astrocytes with the NO donor 1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1
      ium-1,2-diolate (DETA; 100 microM) increased by a factor of 1.4 the rate of
      glucose uptake. We conclude that the increase in GLUT3-driven glucose uptake in
      astrocytes would have a neuroprotective role under conditions in which NO
      formation is combined with hypoglycaemia, such as in brain ischemia.

PMID- 11595754
TI  - Antidepressant drug treatments induce glial cell line-derived neurotrophic factor
      (GDNF) synthesis and release in rat C6 glioblastoma cells.
AB  - Modulation of neurotrophic factors to protect neurons from damage is proposed as
      a novel mechanism for the action of antidepressants. However, the effect of
      antidepressants on modulation of glial cell line-derived neurotrophic factor
      (GDNF), which has potent and widespread effects, remains unknown. Here, we
      demonstrated that long-term use of antidepressant treatment significantly
      increased GDNF mRNA expression and GDNF release in time- and concentration
      dependent manners in rat C6 glioblastoma cells. Amitriptyline treatment also
      increased GDNF mRNA expression in rat astrocytes. GDNF release continued for 24 h
      following withdrawal of amitriptyline. Furthermore, following treatment with
      antidepressants belonging to several different classes (amitriptyline,
      clomipramine, mianserin, fluoxetine and paroxetine) significantly increased GDNF
      release, but which did not occur after treatment with non-antidepressant
      psychotropic drugs (haloperidol, diazepam and diphenhydramine). Amitriptyline
      induced GDNF release was inhibited by U0126 (10 microM), a mitogen-activated
      protein kinase (MAPK)-extracellular signal-related kinase (ERK) kinase (MEK)
      inhibitor, but was not inhibited by H-89 (1 microM), a protein kinase A
      inhibitor, calphostin C (100 nM), a protein kinase C inhibitor and PD 169316 (10
      microM), a p38 mitogen-activated protein kinase inhibitor. These results
      suggested that amitriptyline-induced GDNF synthesis and release occurred at the
      transcriptional level, and may be regulated by MEK/MAPK signalling. The enhanced
      and prolonged induction of GDNF by antidepressants could promote neuronal
      survival, and protect neurons from the damaging effects of stress. This may
      contribute to explain therapeutic action of antidepressants and suggest new
      strategies of pharmacological intervention.

PMID- 11595755
TI  - Oxidative stress induces proorphanin FQ and proenkephalin gene expression in
      astrocytes through p38- and ERK-MAP kinases and NF-kappaB.
AB  - Oxidative stress has been implicated in the pathogenesis of stroke, traumatic
      brain injuries, and neurodegenerative diseases affecting both neuronal and glial
      cells in the CNS. In this study we have demonstrated that reactive oxygen species
      (ROS) dramatically induce the expression of two neuropeptide genes, the opioid
      proenkephalin (pENK) and the opioid-related proorphanin FQ (pOFQ; also known as
      pronociceptin) in primary astrocytes. Hydrogen peroxide (H2O2) treatment dose
      dependently increased pENK and pOFQ mRNA levels with a maximal effect (
      approximately 15-fold increase) being detected at 50 microM concentration.
      Exposing the astrocyte cultures to hypoxia and subsequent re-oxygenation also led
      to a profound elevation of pOFQ and pENK mRNA levels. Western blot analysis and
      immunocytochemistry revealed that H2O2 treatment elicited the phosphorylation and
      nuclear translocation of ERK 1/2 and p38 MAP kinases. Blockade of the p38 or the
      ERK MAP kinase pathways (by SB202190 and PD98059, respectively) prevented the
      H2O2-induced increase in pENK and pOFQ mRNA levels indicating a central role for
      these cascades in the regulation of pOFQ and pENK genes in response to oxidative
      stress. Regulation of pOFQ and pENK gene expression by ERK and p38 activation may
      be mediated through the transcription factor cAMP-response element binding
      protein (CREB). We observed CREB phosphorylation in response to H2O2, which was
      also prevented by SB202190 and PD98059. The nuclear factor-kappaB (NF-kappaB)
      pathway appears to be involved exclusively in the induction of pOFQ transcription
      by H2O2, as NF-kappaB inhibitors antagonized the effect of oxidative stress on
      pOFQ, but not on pENK expression. The profound induction of these genes by
      oxidative stress and these other factors may suggest a role for orphanin FQ and
      enkephalin in injury and stress responses of the CNS and neuropathophysiological
      conditions involving reactive oxygen species.

PMID- 11595756
TI  - Activation of the mitogen-activated protein kinase cascade through nitric oxide
      synthesis as a mechanism of neuritogenic effect of genipin in PC12h cells.
AB  - Prominent neurite outgrowth induced by genipin, a plant-derived iridoid, was
      substantially inhibited by addition of NG-nitro-L-arginine methyl ester (L-NAME),
      a nitric oxide (NO) synthase (NOS) inhibitor, and carboxy-PTIO, an NO scavenger,
      in PC12h cells. Increases of the NADPH-diaphorase activity and neuronal and
      inducible NOS proteins in cells preceded the neurite outgrowth after addition of
      genipin to medium. NO donors could induce the neurite outgrowth dose-dependently
      in the cells. On the other hand, an inhibitor of soluble guanylate cyclase (SGC),
      which is known to be a stimulatory target of NO, abolished greatly the genipin
      induced neurite outgrowth. Addition of extracellular signal-regulated kinase
      (ERK) kinase inhibitors could almost completely abolish the neurite induction. L
      NAME remarkably depressed genipin-stimulated phosphorylation of ERK-1 and -2. A
      neuritogenic effect of nerve growth factor (NGF) in PC12h cells was also
      remarkably inhibited by the NOS inhibitor, NO scavenger and SGC inhibitor. These
      findings suggest that induced NO production followed by cyclic GMP-mediated
      stimulation of the mitogen-activated protein kinase (MAPK) cascade is implicated
      in the neuritogenesis by genipin and NGF in PC12h cells.

PMID- 11595757
TI  - Mutagenesis of the GABA(A) receptor alpha1 subunit reveals a domain that affects
      sensitivity to GABA and benzodiazepine-site ligands.
AB  - We have mutated several amino acids in the region of the GABA(A) receptor alpha1
      subunit predicted to form a small extracellular loop between transmembrane
      domains two and three to investigate its possible role in ligand sensitivity. The
      mutations were S275T, L276A, P277A, V279A, A280S and Y281F. Mutant alpha1
      subunits were co-expressed with beta2 and gamma2 subunits in tsA201 cells or
      Xenopus oocytes. Binding studies revealed that the only mutation that
      significantly affected [3H]Ro15-4513 binding was the V279A substitution which
      reduced the affinity for this ligand. Electrophysiological examination of mutant
      receptors revealed that L276A, P277A and V279A displayed rightward shifts of
      their GABA concentration-response curves, the largest occurring with the L276A
      mutant. The impact of these mutations on allosteric modulation by benzodiazepine
      site ligands was examined. V279A reduced the potency of both flunitrazepam and
      Ro15-4513 but, in each case, their efficacy was enhanced. A280S resulted in a
      decrease in flunitrazepam efficacy without affecting its potency. Additionally,
      P277A and A280S resulted in Ro15-4513 losing its inverse agonist effect at these
      receptors. These results suggest that a domain within this small extracellular
      loop between TMII-TMIII plays a role in determining the sensitivity of GABA(A)
      receptors to both GABA and benzodiazepine-site ligands.

PMID- 11595758
TI  - Dopamine mediates striatal malonate toxicity via dopamine transporter-dependent
      generation of reactive oxygen species and D2 but not D1 receptor activation.
AB  - Intrastriatal injection of the reversible succinate dehydrogenase inhibitor
      malonate results in both chemically induced hypoxia and striatal lesions that are
      similar to those seen in Huntington's disease and cerebral ischaemia. The
      mechanisms leading to neuronal death involve secondary excitotoxicity, the
      release of dopamine from nigrostriatal fibres and the generation of reactive
      oxygen species (ROS) including nitric oxide (NO) and hydroxyl radicals. Here, we
      further investigated the contribution and mechanism of dopamine on malonate
      induced striatal lesions. Prior lesions of the nigrostriatal pathway with 6-OHDA
      or the depletion of striatal dopamine stores by pretreatment with reserpine, an
      inhibitor or the vesicular monoamine transporter type-2 (VMAT2), in combination
      with alpha-methyl-p-tyrosine resulted in a significant reduction of malonate
      induced striatal lesion volumes. This was paralleled by block or reduction of the
      malonate-induced generation of ROS, as measured by the conversions of salicylate
      to 2,3-dihydroxybenzoic acid (2,3-DHBA) using microdialysis. Systemic or
      intrastriatal application of L-DOPA or dopamine, respectively, reconstituted
      malonate toxicity and the generation of ROS in 6-OHDA-lesioned rats. Block of the
      dopamine transporter by GBR12909 did not result in a reduction of malonate
      induced dopamine release, but significantly reduced the generation of hydroxyl
      radicals. The D2 receptor agonist lisuride and the mixed D1 and D2 receptor
      agonist apomorphine, but not the D1 receptor agonist SKF38393, partially restored
      malonate toxicity in 6-OHDA-lesioned rats without increasing the generation of
      ROS. In line with these results sulpiride, an inhibitor of D2 receptors, reduced
      the malonate-induced lesion volume, whereas SCH23390, an inhbitor of D1
      receptors, was ineffective. Our data suggest that malonate-induced dopamine
      toxicity to energetically impaired neurons is mediated by two independent
      pathways: (i) dopamine transporter uptake-dependent, dopamine receptor
      independent generation of ROS, and (ii) excessive stimulation of D2 receptors.

PMID- 11595759
TI  - Apoptosis and necrosis occurring in excitotoxic cell death in isolated chick
      embryo retina.
AB  - Excitotoxic studies using isolated chick embryo retina indicated that such an in
      vitro model provides a valid tool to characterize the effect of different
      agonists for subtypes of glutamate ionotropic receptors. In retinas maintained
      for 24 h in a Krebs medium, after a brief exposure (30 min) to glutamate
      agonists, we compared the effects produced by NMDA and non-NMDA-agonists, such as
      kainic acid (KA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA). Delayed retinal damage was assessed by measuring lactate dehydrogenase
      (LDH) present in the medium after exposure to the previously named agonists.
      Although at high concentrations, both KA and AMPA produced more relevant release
      than NMDA, 7-8% of total retinal LDH was released after exposure to a 50 microM
      concentration of non-NMDA agonists. These values were similar to those obtained
      after 100 microM NMDA. In this regard, retinal tissue appeared to be less
      sensitive to excitotoxicity based on the activation of NMDA receptor subtype. All
      three agents produced histopathological lesions typical for excitotoxic damage. A
      delayed form of excitotoxicity observed in retina segments was predominated by
      necrotic features. However, the activation of apoptotic machinery early during
      the incubation period subsequent to brief exposure to NMDA (100 microM) was also
      present. The activation of caspase enzymes was studied by a fluorometric protease
      activity assay as well as by western blot analysis. Caspase-3-like activity
      reached the highest value within 3 h of incubation after exposure to excitotoxin,
      then the level of enzyme activity declined to lower values. As confirmed by a
      time-related appearance of TUNEL-positive nuclei, apoptotic features appeared to
      be specific for retina response to NMDA. In contrast, the exposure to a 50 microM
      concentration of KA or AMPA induced necrotic cell damage which was evident
      through the incubation, leading to a delayed mechanism of excitotoxicity. These
      observations provide evidence that in the retinal model, with regard to agonist
      concentrations and subtype of glutamate receptors, the cascade of events leading
      to excitotoxicity may result in either apoptotic or necrotic neuronal cell
      damage.

PMID- 11595760
TI  - Internalization of mammalian fluorescent cellular prion protein and N-terminal
      deletion mutants in living cells.
AB  - The cellular prion protein (PrP(c)) is a glycosylphosphatidylinositol (GPI)
      anchored plasma membrane protein whose conformational altered forms (PrP(sc)) are
      known to cause neurodegenerative diseases in mammals. In order to investigate the
      intracellular traffic of mammalian PrP(c) in living cells, we have generated a
      green fluorescent protein (GFP) tagged version of PrP(c). The recombinant protein
      was properly anchored at the cell surface and its distribution pattern was
      similar to that of the endogenous PrP(c), with labeling at the plasma membrane
      and in an intracellular perinuclear compartment. Comparison of the steady-state
      distribution of GFP-PrP(c) and two N-terminal deletion mutants (Delta32-121 and
      Delta32-134), that cause neurological symptoms when expressed in PrP knockout
      mice, was carried out. The mutant proteins accumulated in the plasma membrane at
      the expense of decreased labeling in the perinuclear region when compared with
      GFP-PrP(c). In addition, GFP-PrP(c), but not the two mutants, internalized from
      the plasma membrane in response to Cu2+ treatment and accumulated at a
      perinuclear region in SN56 cells. Our data suggest that GFP-PrP(c) can be used to
      follow constitutive and induced PrP(c) traffic in living cells.

PMID- 11595761
TI  - Maturation of rat brain is accompanied by differential expression of the long and
      short splice variants of G(s)alpha protein: identification of cytosolic forms of
      G(s)alpha.
AB  - Distribution of the alpha subunit of the stimulatory G protein (G(s)alpha) was
      analyzed in membrane and cytosolic (supernatant 200 000 g) fractions from rat
      cortex, thalamus and hippocampus during the course of post-natal development. In
      parallel, changes in beta-adrenoceptor density and adenylyl cyclase activity were
      determined. Long (G(s)alphaL) and short (G(s)alphaS) variants of G(s)alpha were
      assessed by immunoblotting using specific polyclonal antisera reacting with both
      G(s)alpha isoforms. Post-natal development was associated with an increase in the
      total amount of brain G(s)alpha. G(s)alphaL was the dominant isoform of G(s)alpha
      in the membrane fractions of all studied brain regions and its amount increased
      markedly between post-natal day (PD) 1 and 90. The level of membrane-bound
      G(s)alphaS also elevated during post-natal development, but more pronounced
      changes were found in cytosolic G(s)alphaS. Although only a small amount of
      G(s)alphaS (much smaller than G(s)alphaL) was detected among soluble proteins
      shortly after birth, G(s)alphaS prevailed over G(s)alphaL at PD90. The
      G(s)alphaL/G(s)alphaS ratio decreased, respectively, from 3.2 to 1.2 and from 5.0
      to 1.5 in the membrane fractions of cortex and hippocampus, but remained almost
      constant in thalamus between PD1 and 90. More dramatic changes were found in the
      cytosolic fractions of all studied brain regions: the G(s)alphaL/G(s)alphaS ratio
      decreased sharply in cortex (from 14.1 to 0.9), hippocampus (from 3.7 to 0.8),
      and also in thalamus (from 9.5 to 0.5). These results demonstrate that the
      membrane-cytosol balance of G(s)alpha proteins alters dramatically during the
      course of brain development. Both G(s)alphaL and G(s)alphaS were expressed in a
      region- and age-specific manner, which suggests different roles in the maturation
      of the brain tissue. A cyc(-) reconstitutive assay of cytosolic G(s)alpha
      indicated that only approximately 20% of this protein was functional, compared
      with membrane-bound G(s)alpha, and its ability to reconstitute adenylyl cyclase
      activity increased during the course of maturation. The number of beta
      adrenoceptors increased sharply during early post-natal development but only
      slightly in adulthood, and both GTP- and isoproterenol-stimulated adenylate
      cyclase activity reached peak values around PD12.

PMID- 11595762
TI  - Role of capacitative calcium entry on glutamate-induced calcium influx in type-I
      rat cortical astrocytes.
AB  - Capacitative calcium entry (CCE) has been described in a variety of cell types.
      To date, little is known about its role in the CNS, and in particular in the
      cross-talk between glia and neurons. We have first analyzed the properties of CCE
      of astrocytes in culture, in comparison with that of the rat basophilic leukemia
      cell line (RBL-2H3), a model where calcium release-activated Ca2+ (CRAC) channels
      have been unambiguously correlated with CCE. We here show that (i) in astrocytes
      CCE activated by store depletion and Ca2+ influx induced by glutamate share the
      same pharmacological profile of CCE in RBL-2H3 cells and (ii) glutamate-induced
      Ca2+ influx in astrocytes plays a primary role in glutamate-dependent
      intracellular Ca2+ concentration ([Ca2+]i) oscillations, being these latter
      reduced in frequency and amplitude by micromolar concentrations of La3+. Finally,
      we compared the expression of various mammalian transient receptor potential
      genes (TRP) in astrocytes and RBL-2H3 cells. Despite the similar pharmacological
      properties of CCE in these cells, the pattern of TRP expression is very
      different. The involvement of CCE and TRPs in glutamate dependent activation of
      astrocytes is discussed.

PMID- 11595764
TI  - Restricted transport of anti-transferrin receptor antibody (OX26) through the
      blood-brain barrier in the rat.
AB  - Anti-transferrin receptor IgG2a (OX26) transport into the brain was studied in
      rats. Uptake of OX26 in brain capillary endothelial cells (BCECs) was > 10-fold
      higher than isotypic, non-immune IgG2a (Ni-IgG2a) when expressed as % ID/g.
      Accumulation of OX26 in the brain was higher in 15 postnatal (P)-day-old rats
      than in P0 and adult (P70) rats. Iron-deficiency did not increase OX26 uptake in
      P15 rats. Three attempts were made to investigate transport from BCECs further
      into the brain. (i) Using a brain capillary depletion technique, 6-9% of OX26 was
      identified in the post-capillary compartment consisting of brain parenchyma minus
      BCECs. (ii) In cisternal CSF, the volume of distribution of OX26 was higher than
      for Ni-IgG2a when corrected for plasma concentration. (iii) Immunohistochemical
      mapping revealed the presence of OX26 almost exclusively in BCECs; extravascular
      staining was observed only in neurons situated periventricularly. The data
      support the hypothesis of facilitated uptake of OX26 due to the presence of
      transferrin receptors at the blood-brain barrier (BBB). However, OX26
      accumulation in the post-capillary compartment was too small to justify a
      conclusion of receptor-mediated transcytosis of OX26 occurring in BCECs.
      Accumulation of OX26 in the post-capillary component may result from a diphasic
      transport that involves high-affinity accumulation of OX26 by the BCECs, clearly
      exceeding that of Ni-IgG2a, followed by a second transport mechanism that
      releases OX26 non-specifically further into the brain. The periventricular
      localization suggests that OX26 probably also derives from transport across the
      blood-CSF barrier.

PMID- 11595763
TI  - Efflux of a suppressive neurotransmitter, GABA, across the blood-brain barrier.
AB  - In this study, GABA efflux transport from brain to blood was estimated by using
      the brain efflux index (BEI) method. [3H]GABA microinjected into parietal cortex
      area 2 (Par2) of the rat brain was eliminated from the brain with an apparent
      elimination half-life of 16.9 min. The blood-brain barrier (BBB) efflux clearance
      of [3H]GABA was at least 0.153 mL/min/g brain, which was calculated from the
      elimination rate constant (7.14 x 10(-2) x min(-1)) and the distribution volume
      in the brain (2.14 mL/g brain). Direct comparison of the apparent BBB influx
      clearance [3H]GABA (9.29 microL/min/g brain) and the apparent efflux clearance
      (153 microL/min/g brain) indicated that the efflux clearance was at least 16-fold
      greater than the influx clearance. In order to reduce the effect of metabolism in
      the neuronal cells following intracerebral microinjection, we determined the
      apparent efflux of [3H]GABA in the presence of nipecotic acid, a GABA transport
      inhibitor in parenchymal cells, using the BEI method. Under such conditions, the
      elimination of [3H]GABA across the BBB showed saturation and inhibition by
      probenecid in the presence of nipecotic acid. Furthermore, the uptake of [3H]GABA
      by MBEC4 cells was inhibited by GABA, taurine, beta-alanine and nipecotic acid in
      a concentration-dependent manner. It is likely that GABA inhibits the first step
      in the abluminal membrane uptake by brain endothelial cells, and that probenecid
      selectively inhibits the luminal membrane efflux transport process from the brain
      capillary endothelial cells based on the in vivo and in vitro evidence. The BBB
      acts as the efflux pump for GABA to reduce the brain interstitial fluid
      concentration.

PMID- 11595765
TI  - Catecholamine release and uptake in the mouse prefrontal cortex.
AB  - Monitoring the release and uptake of catecholamines from terminals in weakly
      innervated brain regions is an important step in understanding their importance
      in normal brain function. To that end, we have labeled brain slices from
      transgenic mice that synthesize placental alkaline phosphatase (PLAP) on neurons
      containing tyrosine hydroxylase with antibody-fluorochrome conjugate, PLAP-Cy5.
      Excitation of the fluorochrome enables catecholamine neurons to be visualized in
      living tissue. Immunohistochemical fluorescence with antibodies to tyrosine
      hydroxylase and dopamine beta-hydroxylase revealed that the PLAP labeling was
      specific to catecholamine neurons. In the prefrontal cortex (PFC),
      immunohistochemical fluorescence of the PLAP along with staining for dopamine
      transporter (DAT) and norepinephrine transporter (NET) revealed that all three
      exhibit remarkable spatial overlap. Fluorescence from the PLAP antibody was used
      to position carbon-fiber microelectrodes adjacent to catecholamine neurons in the
      PFC. Following incubation with L-DOPA, catecholamine release and subsequent
      uptake was measured and the effect of uptake inhibitors examined. Release and
      uptake in NET and DAT knockout mice were also monitored. Uptake rates in the
      cingulate and prelimbic cortex are so slow that catecholamines can exist in the
      extracellular fluid for sufficient time to travel approximately 100 microm. The
      results support heterologous uptake of catecholamines and volume transmission in
      the PFC of mice.

PMID- 11595766
TI  - Isovolumetric regulation mechanisms in cultured cerebellar granule neurons.
AB  - Cultured cerebellar granule neurons exposed to gradual reductions in osmolarity (
      1.8 mOsm/min) maintained constant volume up to -50% external osmolarity (pi(o)),
      showing the occurrence of isovolumetric regulation (IVR). Amino acids, Cl-, and
      K+ contributed at different phases of IVR, with early efflux threshold for
      [3H]taurine, D-[3H]aspartate (as marker for glutamate) of pi(o) -2% and -19%,
      respectively, and more delayed thresholds of -30% for [3H]glycine and -25% and 
      29%, respectively, for Cl- (125I) and K+ (86Rb). Taurine seems preferentially
      involved in IVR, showing the lowest threshold, the highest efflux rate (five-fold
      over other amino acids) and the largest cell content decrease. Taurine and Cl-
      efflux were abolished by niflumic acid and 86Rb by 15 mM Ba2+. Niflumic acid
      essentially prevented IVR in all ranges of pi(o). Cl--free medium impaired IVR
      when pi(o) decreased to -24% and Ba2+ blocked it only at a late phase of -30%
      pi(o). These results indicate that in cerebellar granule neurons: (i) IVR is an
      active process of volume regulation accomplished by efflux of intracellular
      osmolytes; (ii) the volume regulation operating at small changes of pi(o) is
      fully accounted for by mechanisms sensitive to niflumic acid, with contributions
      of both Cl- and amino acids, particularly taurine; (iii) Cl- contribution to IVR
      is delayed with respect to other niflumic acid-sensitive osmolyte fluxes
      (osmolarity threshold of -25% pi(o)); and (iv), K+ fluxes do not contribute to
      IVR until a late phase (< -30% pi(o)).

PMID- 11595767
TI  - Parallel increases in lipid and protein oxidative markers in several mouse brain
      regions after methamphetamine treatment.
AB  - The neurotoxic actions of methamphetamine (METH) may be mediated in part by
      reactive oxygen species (ROS). Methamphetamine administration leads to increases
      in ROS formation and lipid peroxidation in rodent brain; however, the extent to
      which proteins may be modified or whether affected brain regions exhibit similar
      elevations of lipid and protein oxidative markers have not been investigated. In
      this study we measured concentrations of TBARs, protein carbonyls and monoamines
      in various mouse brain regions at 4 h and 24 h after the last of four injections
      of METH (10 mg/kg/injection q 2 h). Substantial increases in TBARs and protein
      carbonyls were observed in the striatum and hippocampus but not the frontal
      cortex nor the cerebellum of METH-treated mice. Furthermore, lipid and protein
      oxidative markers were highly correlated within each brain region. In the
      hippocampus and striatum elevations in oxidative markers were significantly
      greater at 24 h than at 4 h. Monoamine levels were maximally reduced within 4 h
      (striatal dopamine [DA] by 95% and serotonin [5-HT] in striatum, cortex and
      hippocampus by 60-90%). These decrements persisted for 7 days after METH,
      indicating effects reflective of nerve terminal damage. Interestingly, NE was
      only transiently depleted in the brain regions investigated (hippocampus and
      cortex), suggesting a pharmacological and non-toxic action of METH on the
      noradrenergic nerve terminals. This study provides the first evidence for
      concurrent formation of lipid and protein markers of oxidative stress in several
      brain regions of mice that are severely affected by large neurotoxic doses of
      METH. Moreover, the differential time course for monoamine depletion and the
      elevations in oxidative markers indicate that the source of oxidative stress is
      not derived directly from DA or 5HT oxidation.

PMID- 11595768
TI  - The pituitary adenylate cyclase-activating polypeptide modulates glutamatergic
      calcium signalling: investigations on rat suprachiasmatic nucleus neurons.
AB  - Circadian rhythms generated by the hypothalamic suprachiasmatic nucleus (SCN) are
      synchronized with the external light/dark cycle by photic information transmitted
      directly from the retina via the retinohypothalamic tract (RHT). The RHT contains
      the neurotransmitters glutamate and pituitary adenylate cyclase-activating
      polypeptide (PACAP), which code chemically for 'light' or 'darkness' information,
      respectively. We investigated interactions of PACAP and glutamate by analysing
      effects on the second messenger calcium in individual SCN neurons using the Fura
      2 technique. PACAP did not affect NMDA-mediated calcium increases, but influenced
      signalling cascades of non-NMDA glutamate receptors, which in turn can regulate
      NMDA receptors. On the one hand, PACAP amplified/induced glutamate-dependent
      calcium increases by interacting with alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionate (AMPA)/kainate signalling. This was not related to direct PACAPergic
      effects on the second messengers cAMP and calcium. On the other hand, PACAP
      reduced/inhibited calcium increases elicited by glutamate acting on metabotropic
      receptors. cAMP analogues mimicked this inhibition. Most neurons displaying
      PACAPergic neuromodulation were immunoreactive for vasoactive intestinal
      polypeptide, which is a marker for retinorecipient SCN neurons. The observed
      PACAPergic effects provide a broad range of interactions that allow a fine-tuning
      of the endogenous clock by the integration of 'light' and 'darkness' information
      on the level of single SCN neurons.

PMID- 11595769
TI  - The role of 5-HT1B receptors in the regulation of serotonin cell firing and
      release in the rat brain.
AB  - The release of 5-HT in terminal areas of the rodent brain is regulated by 5-HT1B
      receptors. Here we examined the role of 5-HT1B receptors in the control of 5-HT
      output and firing in the dorsal raphe nucleus (DR), median raphe nucleus (MnR)
      and forebrain of the rat in vivo. The local perfusion (30-300 microM) of the
      selective 5-HT1B receptor agonist CP-93,129 to freely moving rats decreased 5-HT
      release in the DR and more markedly in the MnR. Likewise, 300 microM CP-93,129
      reduced 5-HT output in substantia nigra pars reticulata, ventral pallidum,
      lateral habenula and the suprachiasmatic nucleus. The effect of CP-93,129 was
      prevented by SB-224289, but not by WAY-100635, selective 5-HT1B and 5-HT1A
      receptor antagonists, respectively. SB-224289 did not alter dialysate 5-HT in any
      raphe nuclei. The intravenous administration of the brain-penetrant selective 5
      HT1B receptor agonist CP-94,253 (0.5-2.0 mg/kg) to anesthetized rats decreased
      dialysate 5-HT in dorsal hippocampus and globus pallidus, increased it in MnR and
      left it unaltered in the DR and medial prefrontal cortex. SB-224289, at a dose
      known to block 5-HT1B autoreceptor-mediated effects (5 mg/kg), did not prevent
      the effect of CP-94,253 on MnR 5-HT. The intravenous administration of CP-94,253
      (0.05-1.6 mg/kg) to anesthetized rats increased the firing rate of MnR, but not
      DR-5-HT neurons. The local perfusion of CP-94,253 in the MnR showed a biphasic
      effect, with 5-HT reductions at 0.3-3 microM and increase at 300 microM. These
      results suggest that 5-HT cell firing and release in midbrain raphe nuclei
      (particularly in the MnR) are under control of 5-HT1B receptors. The activation
      of 5-HT1B autoreceptors (possibly located on 5-HT nerve endings and/or
      varicosities within DR and MnR) reduces 5-HT release. The effects of higher
      concentrations of 5-HT1B receptor agonists seem more compatible with the
      activation of 5-HT1B heteroreceptors on inhibitory neurons.

PMID- 11595770
TI  - Prevalence between different alpha subunits performing the benzodiazepine binding
      sites in native heterologous GABA(A) receptors containing the alpha2 subunit.
AB  - The presence of two heterologous alpha subunits and a single benzodiazepine
      binding site in the GABA(A) receptor implicates the existence of
      pharmacologically active and inactive alpha subunits. This fact raises the
      question of whether a particular alpha subtype could predominate performing the
      benzodiazepine binding site. The hippocampal formation expresses high levels of
      alpha subunits with different benzodiazepine binding properties (alpha1, alpha2
      and alpha5). Thus, we first demonstrated the existence of alpha2-alpha1 (36.3 +/-
      5.2% of the alpha2 population) and alpha2-alpha5 (20.2 +/- 2.1%) heterologous
      receptors. A similar alpha2-alpha1 association was observed in cortex. This
      association allows the direct comparison of the pharmacological properties of
      heterologous native GABA(A) receptors containing a common (alpha2) and a
      different (alpha1 or alpha5) alpha subunit. The alpha2 subunit pharmacologically
      prevailed over the alpha1 subunit in both cortex and hippocampus (there was an
      absence of high-affinity binding sites for Cl218,872, zolpidem and [3H]zolpidem).
      This prevalence was directly probed by zolpidem displacement experiments in
      alpha2-alpha1 double immunopurified receptors (K(i) = 295 +/- 56 nM and 200 +/- 8
      nM in hippocampus and cortex, respectively). On the contrary, the alpha5 subunit
      pharmacologically prevailed over the alpha2 subunit (low- and high-affinity
      binding sites for zolpidem and [3H]L-655,708, respectively). This prevalence was
      probed in alpha2-alpha5 double immunopurified receptors. Zolpidem displayed a
      single low-affinity binding site (K(i) = 1.73 +/- 0.54 microM). These results
      demonstrated the existence of a differential dominance between the different
      alpha subunits performing the benzodiazepine binding sites in the native GABA(A)
      receptors.

PMID- 11595771
TI  - Regulated expression of an actin-associated protein, synaptopodin, during long
      term potentiation.
AB  - We report NMDA receptor-dependent expression of synaptopodin mRNA in the dentate
      granule cells of the hippocampus following induction of long-term potentiation
      (LTP) in vivo. Synaptopodin did not belong to immediate-early genes, as de novo
      protein synthesis was required for the induction of synaptopodin gene
      transcription. An increased level of synaptopodin mRNA was observed at 75 min and
      3.5 h after the onset of LTP. Importantly, there was correlation between the
      induction of mRNA expression and the persistence of LTP. Synaptopodin
      immunoreactivity was elevated specifically in synaptic layers, middle and outer
      molecular layers of dentate gyrus where LTP was induced. As synaptopodin is an
      actin-associated protein present in spine neck and implicated in the modulation
      of cell morphology, our results suggest that synaptopodin, by regulating the
      dynamics of the actin cytoskeleton, contributes to the morphological change in
      spine shape considered to be important for the maintenance of synaptic
      plasticity.

PMID- 11595772
TI  - Noradrenaline provides long-term protection to dopaminergic neurons by reducing
      oxidative stress.
AB  - To better understand the neurotrophic function of the neurotransmitter
      noradrenaline, we have developed a model of mesencephalic cultures in which we
      find low concentrations (0.3-10 microM) of noradrenaline to be remarkably
      effective in promoting long-term survival and function of dopaminergic neurons.
      This protective action reproduced the effect of caspase inhibition. It was
      atypical in that it occurred independently of adrenoceptor activation and was
      mimicked by some antioxidants, redox metal chelators and the hydroxyl radical
      detoxifying enzyme catalase. Interestingly, intracellular reactive oxygen species
      (ROS) were drastically reduced by treatment with noradrenaline, indicating that
      the neurotransmitter itself acted as an antioxidant. Prevention of oxidative
      stress was, however, independent of the glutathione antioxidant defense system.
      Chemical analogues of noradrenaline bearing two free hydroxyl groups in the ortho
      position of the aromatic ring (o-catechols), as well as o-catechol itself,
      mimicked the survival promoting effects of the neurotransmitter, suggesting that
      this diphenolic structure was critical for both neuroprotection and reduction of
      ROS production. Paradoxically, the autoxidation of noradrenaline and the ensuing
      production of quinone metabolites may be required for both effects, as the
      neurotransmitter was spontaneously and rapidly degraded over time in the culture
      medium. These results support the concept that central noradrenergic mechanisms
      have a neuroprotective role, perhaps in part by reducing oxidative stress.

PMID- 11595773
TI  - Developmental and regional distribution of aspartoacylase in rat brain tissue.
AB  - The function of N-acetyl-aspartate (NAA), a predominant molecule in the brain,
      has not yet been determined. However, NAA is commonly used as a putative marker
      of viable neurones. To investigate the possible function of NAA, we determined
      the anatomical, developmental and cellular distribution of aspartoacylase, which
      catalyses the hydrolysis of NAA. Levels of aspartoacylase activity were measured
      during postnatal development in several brain regions. The differential
      distribution of aspartoacylase activity in purified populations of cells derived
      from the rat CNS was also investigated. The developmental and anatomical
      distribution of aspartoacylase correlated with the maturation of white matter
      tracts in the rat brain. Activity increased markedly after 7 days and coincided
      with the time course for the onset of myelination in the rat brain. Gray matter
      showed little activity or developmental trend. There was a 60-fold excess in
      optic nerve (a white matter tract) when compared with cortex at 21 days of
      development. In the adult brain there was a 18-fold difference in corpus callosum
      compared with cortex (stripped of corpus callosum). Cellular studies demonstrated
      that purified cortical neurons and cerebellar granular neurones have no activity.
      Primary O-2A progenitor cells had moderate activity, with three-fold higher
      activity in immature oligodendrocyte and 13-fold increase in mature
      oligodendrocytes (myelinating cells of the CNS). The highest activity was seen in
      type-2 astrocytes (20-fold difference compared with O-2A progenitors) derived
      from the same source. Aspartoacylase activity increased with time in freshly
      isolated astrocytes, with significantly higher activity after 15 days in culture.
      We conclude that aspartoacylase activity in the developing postnatal brain
      corresponds with maturation of myelination, and that the cellular distribution is
      limited to glial cells.

PMID- 11595774
TI  - Induction of nuclear factor-kappaB in nucleus accumbens by chronic cocaine
      administration.
AB  - DeltaFosB is a Fos family transcription factor that is induced by chronic
      exposure to cocaine and other drugs of abuse in the nucleus accumbens and related
      striatal regions, brain regions that are important for the behavioral effects of
      these drugs. To better understand the mechanisms by which DeltaFosB contributes
      to the effects of chronic drug treatment, we used DNA microarray analysis to
      identify genes that are regulated in the nucleus accumbens upon DeltaFosB
      expression in inducible bitransgenic mice. One of the most highly regulated genes
      was that encoding a subunit of another transcription factor, nuclear factor
      kappaB (NF-kappaB). Subsequent experiments confirmed the induction of NF-kappaB
      in the nucleus accumbens of mice overexpressing DeltaFosB as well as in wild-type
      mice treated chronically, but not acutely, with cocaine. These results establish
      NF-kappaB as a putative target for DeltaFosB and implicate NF-kappaB signaling
      pathways in the long-term adaptations of nucleus accumbens neurons to cocaine.

PMID- 11595775
TI  - Influence of leptin on changes in body fat during growth in African American and
      white children.
AB  - OBJECTIVE: The aim of this study was to determine whether initial levels or
      temporal changes in fasting leptin were associated with longitudinal changes in
      body-fat mass in children. RESEARCH METHODS AND PROCEDURES: The study group
      consisted of 85 children (42 white and 43 African American) with a mean initial
      age of 8.1 +/- 0.1 years. The children had between three and six annual visits
      for repeated measurements of body composition by DXA and fasting leptin level.
      Fat mass and fasting leptin level were not normally distributed and were log
      transformed. Data were analyzed using SAS Proc mixed growth models, with log fat
      as the dependent variable. RESULTS: Initial leptin level was a significant
      predictor of the change in fat mass over time (p < 0.0001), with high initial
      leptin levels resulting in increased fat gain, independent of initial fat levels.
      This relationship remained significant when the data were analyzed separately by
      race (whites, p < 0.0001; African Americans, p = 0.008). The relationship between
      the initial level of leptin and the change in fat mass was not modified by race,
      sex, or Tanner Stage. The rate of change in leptin during the study was
      significantly related to the rate of change in fat mass in African Americans (p =
      0.008) but not in whites (p = 0.490). DISCUSSION: In conclusion, high fasting
      leptin level at the start of the study was significantly associated with
      increasing fat mass in this cohort, indicating that the children may be
      developing resistance to the effects of leptin.

PMID- 11595776
TI  - Orlistat inhibits dietary cholesterol absorption.
AB  - OBJECTIVE: Orlistat decreases the absorption of dietary triglycerides by
      inhibiting intestinal lipases. Orlistat therapy is associated with a greater
      decline in plasma low-density lipoprotein-cholesterol concentrations than that
      expected from weight loss alone. Therefore, we evaluated the effect of orlistat
      treatment on dietary cholesterol absorption as a possible mechanism for the
      independent effect of orlistat on plasma cholesterol concentration. RESEARCH
      METHODS AND PROCEDURES: Cholesterol absorption from a standardized meal,
      containing 72 mg of cholesterol, was determined in 18 subjects with class II
      abdominal obesity (BMI, 35.0 to 39.9 kg/m(2)) by simultaneous administration of
      intravenous ([(2)H(6)] cholesterol) and oral ([(2)H(5)] cholesterol) cholesterol
      tracers. In protocol 1 (n = 9), cholesterol absorption was determined on two
      different occasions, 10 to 20 days apart, to assess the reproducibility of the
      tracer method. In protocol 2 (n = 9), cholesterol absorption was determined with
      and without orlistat therapy in a prospective, randomized, crossover design to
      assess the effect of orlistat on cholesterol absorption. RESULTS: In protocol 1,
      cholesterol absorption from the test meal was the same on both occasions (53 +/-
      5% and 51 +/- 5%). In protocol 2, orlistat treatment caused a 25% reduction in
      cholesterol absorption, from 59 +/- 6% to 44 +/- 5% (p < 0.01). DISCUSSION: These
      data demonstrate that orlistat inhibits dietary cholesterol absorption, which may
      have beneficial effects on lipoprotein metabolism in obese subjects that are
      independent of weight loss itself.

PMID- 11595777
TI  - Body composition of African American and white children: a 2-year follow-up of
      the BAROC study.
AB  - OBJECTIVE: To evaluate the 2-year changes in body composition of white and
      African American boys and girls. RESEARCH METHODS AND PROCEDURES: A total of 114
      boys and girls ages 12 to 14 years with equal sex and ethnic distribution between
      African American and white races participated in measurements of body composition
      using DXA, underwater weighing (densitometry), skinfold thickness, corporal
      diameters, circumferences, isotope dilution (H(2)(18)O), and bioelectric
      impedance. RESULTS: Sixty-eight of the 114 children advanced from Tanner Stages 1
      and 2 to Tanner Stages 3 to 5 over a 2-year period. More than 50% of the children
      were in the top 15th percentile according to normative data for body mass index
      but not for triceps skinfold. All measures except for percentage of fat, density,
      and four of the six skinfolds increased significantly during the 2 years, with no
      differences between races, genders, or fat group. The boys who advanced in Tanner
      Stage reduced their percentage of fat and a number of skinfolds and increased
      their lean body mass, but the girls did not. The percentage of water was
      significantly higher in the fatter children and declined significantly over 2
      years. Most children remained in the same quartile of body fat, lean body mass,
      and bone mineral content over 2 years. DISCUSSION: The data are consistent with
      the hypothesis that over 2 years, growth is the major determinant of changing
      body composition, with body-fat group and sexual maturation being additional
      variables.

PMID- 11595778
TI  - Obesity and sarcopenia after menopause are reversed by sex hormone replacement
      therapy.
AB  - OBJECTIVE: Menopause is linked to an increase in fat mass and a decrease in lean
      mass exceeding age-related changes, possibly related to reduced output of ovarian
      steroids. In this study we examined the effect of combined postmenopausal hormone
      replacement therapy (HRT) on the total and regional distribution of fat and lean
      body mass. RESEARCH METHODS AND PROCEDURES: Sixteen healthy postmenopausal women
      (age: 55 +/- 3 years) were studied in a placebo-controlled, crossover study and
      were randomized to 17beta estradiol plus cyclic norethisterone acetate (HRT) or
      placebo in two 12-week periods separated by a 3-month washout. Total and regional
      body composition was measured by DXA at baseline and in the 10th treatment week
      in both periods. Changes were compared by a paired Student's t test. RESULTS: The
      change in body weight during HRT was equal to the change during placebo (-24.6 g
      vs. -164 g, p = 0.42), but relative fat mass was significantly reduced (-0.5% vs.
      +1.24%, p < 0.01). During HRT, compared with during placebo, lean body mass
      increased (+347 g vs. -996 g, p < 0.01) and total fat mass decreased (-400 g vs.
      +836 g, p = 0.06). Total bone mineral content increased (+28.9 g vs. -4.4 g, p =
      0.04) and abdominal fat decreased (-185 g vs. +253 g, p = 0.04) during HRT
      compared with placebo. DISCUSSION: HRT is linked to the reversal of both
      menopause-related obesity and loss of lean mass, without overall change in body
      weight. The increase in lean body mass during HRT is likely explained by muscle
      anabolism, which in turn, prevents disease in the elderly.

PMID- 11595779
TI  - Leptin does not play a major role in platelet aggregation in obesity and leptin
      deficiency.
AB  - OBJECTIVE: A recent study suggested that high concentrations of leptin enhance
      platelet aggregations. Therefore, the aim of this study was to investigate
      whether platelet aggregation is altered in patients with leptin gene mutations
      compared with obese subjects or controls. RESEARCH METHODS AND PROCEDURES: Four
      men (one homozygous man and his three heterozygous brothers) carrying a leptin
      gene mutation; 20 age-matched, healthy, unrelated men; and 18 age-matched obese
      men were enrolled in the study. Adenosine diphosphate (ADP)-, collagen-, and
      epinephrine-induced platelet aggregation were evaluated in all individuals.
      RESULTS: Our results show that patients with the leptin gene mutation (both the
      homozygous and heterozygous patients) had significantly higher ADP-induced (78.3
      +/- 3.4% vs. 57.9 +/- 9.3%, p = 0.001), collagen-induced (78.1 +/- 2.9% vs. 56.7
      +/- 9.3%, p = 0.007), and epinephrine-induced (76.5 +/- 9.2% vs. 59.5 +/- 7.70%,
      p = 0.003) platelet aggregation compared with controls. However, ADP-, collagen-,
      or epinephrine-induced platelet aggregations were similar to those in obese
      patients. Platelet aggregation responses to a combination of pretreatment with
      leptin at concentrations of 20, 50, 100, or 500 ng/mL for 5 minutes and ADP at
      concentrations of 2 micromol/liter also were evaluated. However, we did not find
      significant increases in platelet aggregation even at high concentrations of
      leptin (100 or 500 ng/mL) in leptin-deficient patients, obese subjects, or
      controls. DISCUSSION: Our data show that similar to findings in obese humans,
      homozygous or heterozygous leptin deficiency is associated with increased
      platelet aggregation compared with controls, and that higher concentrations of
      leptin do not increase platelet aggregation.

PMID- 11595780
TI  - No decrease in free IGF-I with increasing insulin in obesity-related insulin
      resistance.
AB  - OBJECTIVE: Different facts suggest that the insulin growth factor (IGF)/ insulin
      growth factor-binding protein (IGFBP) system may be regulated by factors other
      than growth hormone. It has been proposed that, in healthy subjects, free IGF-I
      plays a role in glucose metabolism. The role of free IGF-I in glucose homeostasis
      in insulin resistance is poorly understood. This study was undertaken to evaluate
      the effects of acute changes in plasma glucose and insulin levels on free IGF-I
      and IGFBP-1 in obese and non-obese subjects. RESEARCH METHODS AND PROCEDURES:
      Nineteen lean and 24 obese subjects were investigated. A frequently sampled
      intravenous glucose tolerance test was performed. Free IGF-I and IGFBP-1 were
      determined at 0, 19, 22, 50, 100, and 180 minutes. RESULTS: Basal free IGF-I
      levels tended to be higher and IGFBP-1 lower in obese than in lean subjects.
      IGFBP-1 levels inversely correlated with basal insulin concentration. To
      determine the effects of insulin on the availability of free IGF-I and IGFBP-1,
      changes in their plasma concentrations were measured during a frequently sampled
      intravenous glucose tolerance test. After insulin administration, a significant
      suppression of free IGF-I at 22% was observed in lean subjects. In contrast,
      plasma-free IGF-I levels remained essentially unchanged in the obese group. The
      differences between both groups were statistically significant at 100 minutes (p
      < 0.01) and 180 minutes (p < 0.05). Serum IGFBP-1 was suppressed to a similar
      extent in both groups. DISCUSSION: These data suggest that the concentrations of
      free IGF-I and IGFBP-1 are differentially regulated by obesity. Obesity-related
      insulin resistance leads to unsuppressed free IGF-I levels.

PMID- 11595781
TI  - Cardiac parasympathetic activity is increased by weight loss in healthy obese
      women.
AB  - OBJECTIVE: We studied the effect of weight reduction on cardiac parasympathetic
      activity (PSA) in obese women. We also studied the relationship between the
      changes of PSA, resting energy expenditure (REE), and major cardiovascular risk
      factors. RESEARCH METHODS AND PROCEDURES: Changes of cardiac vagal tone, an index
      of PSA, REE, and major cardiovascular risk factors, were measured in 52 healthy
      obese women after a 6-month weight reduction. Ten of the women were remeasured at
      12 and 24 months. Cardiac vagal tone was assessed by a vagal tone monitor and REE
      by indirect calorimeter. RESULTS: Cardiac vagal tone increased significantly (p =
      0.046), averaging a 9.5% weight loss in 6 months. The vagal tone increased
      further with weight loss during the following 6 months, and thereafter, it
      declined with weight regain. The increase of cardiac vagal tone correlated
      significantly with decreases of body weight, fat mass, waist circumference, serum
      insulin, and heart rate. REE adjusted for fat-free mass and age did not change
      with weight loss and was not related to cardiac vagal tone at any time-point.
      DISCUSSION: Cardiac PSA activity increases with weight loss in obese women. This
      increase may not be maintained long-term if body weight is regained. The rise of
      cardiac PSA is correlated with decreases of body fat mass, abdominal fat, serum
      insulin, and heart rate. Cardiac PSA is not related to REE.

PMID- 11595782
TI  - Larger hip circumference independently predicts health and longevity in a Swedish
      female cohort.
AB  - OBJECTIVE: The waist circumference is widely viewed as a simple but effective
      measure for assessing obesity-related health risks, whereas measurement of the
      hip circumference is not currently prioritized. This study examines health risks
      associated specifically with hip circumference in a cohort of Swedish women, to
      determine whether information may be lost by excluding the hip circumference from
      health surveys. RESEARCH METHODS AND PROCEDURES: The subjects described in this
      report constitute a population-based sample of 38- to 60-year-old women who
      underwent anthropometric examinations in 1968. The 24-year incidence rates have
      been ascertained for myocardial infarction, combined cardiovascular diseases, and
      diabetes. All-cause, cardiovascular, and myocardial infarction mortality also
      were evaluated. RESULTS: Hip circumference was a significant independent inverse
      risk estimator for all endpoints studied. Using Cox regression with adjustment
      for age, smoking, body mass index, and waist circumference, the remaining
      variability associated with larger hips was associated with significantly fewer
      adverse health outcomes. The hip circumference became statistically informative
      after body mass index adjustment. The strongest protective associations were
      observed for cardiovascular disease and diabetes endpoints, although significant
      trends were also seen for total mortality. Considering hip and waist
      simultaneously, the strength of the inverse association for large hips generally
      exceeded the positive association for waist. DISCUSSION: Recent interest in the
      waist circumference as an effective screening tool has taken the focus off of the
      hip circumference. The present results suggest that collection of hip
      measurements should not be discontinued in assessment of obesity-related risk
      status and health promotion.

PMID- 11595783
TI  - Gender differences in the relationship between personality dimensions and
      relative body weight.
AB  - OBJECTIVE: The relationship between body mass index (BMI: kg/m(2)) and
      personality seems to differ for men and women, although these effects may be
      driven by the extremes of the BMI distribution. It is unclear whether these
      associations exist for most individuals in the relatively normal range of BMI
      scores, excluding the thinnest and heaviest extremes in the population. We tested
      the association of BMI with neuroticism, extraversion, and psychoticism with a
      trimmed BMI sample. RESEARCH METHODS AND PROCEDURES: Using a cross-sectional
      design, we tested the association of BMI with the aforementioned psychological
      variables in a British population-based sample. Participants were 7889 adult men
      and women (30 to 50 years old) selectively sampled from four counties in west
      England. Participants reported their height and weight and completed the Eysenck
      Personality Inventory (EPQ). We tested the association of BMI with the EPQ
      subscales among individuals with BMI >or=19.16 kg/m(2) and <or=37.78 kg/m(2),
      i.e., the approximate 5th and 95th percentiles. RESULTS: Despite elimination of
      extreme BMIs, different associations between BMI and EPQ subscales emerged for
      men and women. Among women, increasing BMI was significantly associated with
      increased neuroticism and reduced extraversion. Among men, increasing BMI was
      associated with increased extraversion and psychoticism. In all cases, the
      magnitude of the association was very small. DISCUSSION: Increasing BMI was
      associated with potentially poorer adjustment among women but better adjustment
      among men. These findings are consistent with recent reports and, taken together,
      suggest that these patterns are not accounted for solely by the extremes of the
      BMI distribution.

PMID- 11595784
TI  - Intraobserver and interobserver reliability of waist circumference and the waist
      to-hip ratio.

PMID- 11595785
TI  - Long-term medication use and weight loss maintenance: an observational study.

PMID- 11595786
TI  - Accumulating evidence for differences during preadipocyte development: Focus on
      "Differential gene expression in white and brown preadipocytes".

PMID- 11595787
TI  - Gene expression profiling of the response to thermal injury in human cells.
AB  - The genetic response of human cells to sublethal thermal injury was assessed by
      gene expression profiling, using macroarrays containing 588 complementary known
      genes. At 1, 4, 8, and 24 h following thermal injury, RNA was isolated, and a
      cDNA copy was generated incorporating (33)P and hybridized to Atlas arrays. About
      one-fifth of the genes on the membrane exhibited a significant elevation or
      depression in expression (>/=2-fold) by 4 h posttreatment. Genes for heat shock
      proteins (HSPs) were upregulated as well as genes for transcription factors,
      growth regulation, and DNA repair. Cluster analysis was performed to assess
      temporal relationships between expression of genes. Translation of mRNA for some
      expressed genes, including HSP70 and HSP40, was corroborated by Western blotting.
      Gene expression profiling can be used to determine information about gene
      responses to thermal injury by retinal pigment epithelium cells following
      sublethal injury. The induction of gene expression following thermal injury
      involves a number of genes not previously identified as related to the stress
      response.

PMID- 11595788
TI  - Differential gene expression in white and brown preadipocytes.
AB  - White (WAT) and brown (BAT) adipose tissue are tissues of energy storage and
      energy dissipation, respectively. Experimental evidence suggests that brown and
      white preadipocytes are differentially determined, but so far not much is known
      about the genetic control of this determination process. The aim of this study
      was to identify differentially expressed genes involved in brown and white
      preadipocyte development. Using representational difference analysis (cDNA RDA)
      and DNA microarray screening, we identified four genes with higher expression in
      white preadipocytes (three different complement factors and delta-6 fatty acid
      desaturase) and seven genes with higher expression levels in brown preadipocytes,
      of which three are structural genes implicated in cell adhesion and cytoskeleton
      organization (fibronectin, alpha-actinin-4, metargidin) and four that might
      function in gene transcription and protein synthesis (vigilin, necdin, snRNP
      polypeptide A, and a homolog to human hepatocellular carcinoma-associated
      protein). The expression profile of these genes was analyzed during preadipocyte
      differentiation, upon beta-adrenergic stimulation, and in WAT and BAT tissue in
      vivo compared with references genes such as peroxisome proliferator-activated
      receptor-gamma (PPARgamma), uncoupling protein 1 (UCP1), cytochrome c oxidase.

PMID- 11595789
TI  - Two-hybrid analysis of the Saccharomyces cerevisiae 26S proteasome.
AB  - A two-hybrid screen against an activation domain array of Saccharomyces
      cerevisiae proteins was carried out for 31 yeast proteasome proteins. Fifty-five
      putative interactions were identified: 21 between components of the proteasome
      complex and 34 between proteasome proteins and other proteins. Many of these
      latter interactions involved either proteins of the ubiquitin pathway, cell cycle
      proteins, protein kinases or a translation initiation factor subunit. The role of
      eleven proteins associated with proteasome function by these screens was analyzed
      by examining the corresponding deletion strains for temperature sensitivity and
      canavanine sensitivity and for the stability of a ubiquitin-beta-galactosidase
      fusion protein. These assays additionally implicated three proteins, Bim1, Ump1,
      and YKL171W, in proteasome function. This study demonstrates the utility of
      genome-wide two-hybrid assays as an entry point for the further analysis of a
      large protein complex.

PMID- 11595790
TI  - Mast cell regulation of inflammation and gene expression during antigen-induced
      bladder inflammation in mice.
AB  - Mast cell numbers are significantly increased in bladder disorders including
      malignancy and interstitial cystitis, but their precise role has been difficult
      to determine. We characterized the role of mast cells on gene regulation
      associated with antigen-induced bladder inflammation in mice. For this purpose,
      we examined the responses in mast cell-deficient (Kit(W)/Kit(W-v)), congenic
      normal (+/+), and Kit(W)/Kit(W-v) mice that were reconstituted with bone marrow
      stem cells (BMR) to restore mast cells. All mice were actively sensitized and
      challenged intravesically with either saline or specific antigen. Bladder
      inflammation occurred in +/+ and BMR but not the Kit(W)/Kit(W-v) mice. Gene
      expression was determined using mouse cDNA expression arrays. Self-organizing
      maps, performed without preconditions, indicated gene expression changes
      dependent on the presence of mast cells. These genes were upregulated in bladders
      isolated from antigen challenge of +/+, not altered in Kit(W)/Kit(W-v), and were
      upregulated in BMR mice. Taken together these results demonstrate an important
      role for mast cells in allergic cystitis and indicate that mast cells can alter
      their environment by regulating tissue gene expression.

PMID- 11595791
TI  - A statistical method for flagging weak spots improves normalization and ratio
      estimates in microarrays.
AB  - Over the last few years, there has been a dramatic increase in the use of cDNA
      microarrays to monitor gene expression changes in biological systems. Data from
      these experiments are usually transformed into expression ratios between
      experimental samples and a common reference sample for subsequent data analysis.
      The accuracy of this critical transformation depends on two major parameters: the
      signal intensities and the normalization of the experiment vs. reference signal
      intensities. Here we describe and validate a new model for microarray signal
      intensity that has one multiplicative variation and one additive background
      variation. Using replicative experiments and simulated data, we found that the
      signal intensity is the most critical parameter that influences the performance
      of normalization, accuracy of ratio estimates, reproducibility, specificity, and
      sensitivity of microarray experiments. Therefore, we developed a statistical
      procedure to flag spots with weak signal intensity based on the standard
      deviation (delta(ij)) of background differences between a spot and the
      neighboring spots, i.e., a spot is considered as too weak if the signal is weaker
      than cdelta(ij). Our studies suggest that normalization and ratio estimates were
      unacceptable when this threshold (c) is small. We further showed that when a
      reasonable compromise of c (c = 6) is applied, normalization using trimmed mean
      of log ratios performed slightly better than global intensity and mean of ratios.
      These studies suggest that decreasing the background noise is critical to improve
      the quality of microarray experiments.

PMID- 11595792
TI  - DNA microarray analysis of gene expression in endothelial cells in response to 24
      h shear stress.
AB  - The recently developed DNA microarray technology provides a powerful and
      efficient tool to rapidly compare the differential expression of a large number
      of genes. Using the DNA microarray approach, we investigated gene expression
      profiles in cultured human aortic endothelial cells (HAECs) in response to 24 h
      of laminar shear stress at 12 dyn/cm(2). This relatively long-term shearing of
      cultured HAECs led to the modulation of the expression of a number of genes.
      Several genes related to inflammation and EC proliferation were downregulated,
      suggesting that 24-h shearing may keep ECs in a relatively noninflammatory and
      nonproliferative state compared with static cells. Some genes were significantly
      upregulated by the 24-h shear stress; these includes genes involved in EC
      survival and angiogenesis (Tie2 and Flk-1) and vascular remodeling (matrix
      metalloproteinase 1). These results provide information on the profile of gene
      expression in shear-adapted ECs, which is the case for the native ECs in the
      straight part of the aorta in vivo.

PMID- 11595793
TI  - Auxin and the power of the proteasome in plants.

PMID- 11595794
TI  - Plant biology 2001.

PMID- 11595795
TI  - Identification of a signal that distinguishes between the chloroplast outer
      envelope membrane and the endomembrane system in vivo.
AB  - Certain small outer envelope membrane proteins of chloroplasts are encoded by the
      nuclear genome without a cleavable N-terminal transit peptide. We investigated in
      vivo the targeting mechanism of AtOEP7, an Arabidopsis homolog of the small outer
      envelope membrane protein. AtOEP7 was expressed as a fusion protein with the
      green fluorescent protein (GFP) either transiently in protoplasts or stably in
      transgenic plants. In either case, fluorescence microscopy of transformed cells
      and protein gel blot analysis of fractionated proteins confirmed that the
      AtOEP7:GFP fusion protein was targeted to the chloroplast outer envelope
      membrane. In vivo targeting experiments revealed that two regions, the
      transmembrane domain (TMD) and its C-terminal neighboring seven-amino acid
      region, were necessary and sufficient for targeting to the chloroplast outer
      membrane. Substitution of aspartic acid or lysine residues with glycine residues
      or scrambling of the amino acid sequence of the seven-amino acid region caused
      mistargeting to the plasma membrane. Although the amino acid sequence of the TMD
      is not important for targeting, amino acid residues with large side chains
      inhibited targeting to the chloroplasts and resulted in the formation of large
      aggregates in the protoplasts. In addition, introduction of a proline residue
      within the TMD resulted in inhibition of targeting. Finally, a fusion protein,
      AtOEP7:NLS:GFP, was targeted efficiently to the chloroplast envelope membranes
      despite the presence of a nuclear localization signal. On the basis of these
      results, we conclude that the seven-amino acid region and the TMD are
      determinants for targeting to the chloroplast outer envelope membrane. The seven
      amino acid region plays a critical role in AtOEP7 evading the endomembrane system
      and entering the chloroplast pathway, and the TMD plays critical roles in
      migration to the chloroplasts and/or subsequent insertion into the membrane.

PMID- 11595796
TI  - The DEFECTIVE IN ANTHER DEHISCIENCE gene encodes a novel phospholipase A1
      catalyzing the initial step of jasmonic acid biosynthesis, which synchronizes
      pollen maturation, anther dehiscence, and flower opening in Arabidopsis.
AB  - The Arabidopsis mutant defective in anther dehiscence1 (dad1) shows defects in
      anther dehiscence, pollen maturation, and flower opening. The defects were
      rescued by the exogenous application of jasmonic acid (JA) or linolenic acid,
      which is consistent with the reduced accumulation of JA in the dad1 flower buds.
      We identified the DAD1 gene by T-DNA tagging, which is characteristic to a
      putative N-terminal transit peptide and a conserved motif found in lipase active
      sites. DAD1 protein expressed in Escherichia coli hydrolyzed phospholipids in an
      sn-1-specific manner, and DAD1-green fluorescent protein fusion protein expressed
      in leaf epidermal cells localized predominantly in chloroplasts. These results
      indicate that the DAD1 protein is a chloroplastic phospholipase A1 that catalyzes
      the initial step of JA biosynthesis. DAD1 promoter::beta-glucuronidase analysis
      revealed that the expression of DAD1 is restricted in the stamen filaments. A
      model is presented in which JA synthesized in the filaments regulates the water
      transport in stamens and petals.

PMID- 11595797
TI  - The disease resistance signaling components EDS1 and PAD4 are essential
      regulators of the cell death pathway controlled by LSD1 in Arabidopsis.
AB  - Specific recognition of pathogens is mediated by plant disease resistance (R)
      genes and translated into a successful defense response. The extent of associated
      hypersensitive cell death varies from none to an area encompassing cells
      surrounding an infection site, depending on the R gene activated. We constructed
      double mutants in Arabidopsis between positive regulators of R function and a
      negative regulator of cell death, LSD1, to address whether genes required for
      normal R function also regulate the runaway cell death observed in lsd1 mutants.
      We report here that EDS1 and PAD4, two signaling genes that mediate some but not
      all R responses, also are required for runaway cell death in the lsd1 mutant.
      Importantly, this novel function of EDS1 and PAD4 is operative when runaway cell
      death in lsd1 is initiated through an R gene that does not require EDS1 or PAD4
      for disease resistance. NDR1, another component of R signaling, also contributes
      to the control of plant cell death. The roles of EDS1 and PAD4 in regulating lsd1
      runaway cell death are related to the interpretation of reactive oxygen
      intermediate-derived signals at infection sites. We further demonstrate that the
      fate of superoxide at infection sites is different from that observed at the
      leading margins of runaway cell death lesions in lsd1 mutants.

PMID- 11595798
TI  - A humidity-sensitive Arabidopsis copine mutant exhibits precocious cell death and
      increased disease resistance.
AB  - The copines are a newly identified class of calcium-dependent, phospholipid
      binding proteins that are present in a wide range of organisms, including
      Paramecium, plants, Caenorhabditis elegans, mouse, and human. However, the
      biological functions of the copines are unknown. Here, we describe a humidity
      sensitive copine mutant in Arabidopsis. Under nonpermissive, low-humidity
      conditions, the cpn1-1 mutant displayed aberrant regulation of cell death that
      included a lesion mimic phenotype and an accelerated hypersensitive response
      (HR). However, the HR in cpn1-1 showed no increase in sensitivity to low pathogen
      titers. Low-humidity-grown cpn1-1 mutants also exhibited morphological
      abnormalities, increased resistance to virulent strains of Pseudomonas syringae
      and Peronospora parasitica, and constitutive expression of pathogenesis-related
      (PR) genes. Growth of cpn1-1 under permissive, high-humidity conditions abolished
      the increased disease resistance, lesion mimic, and morphological mutant
      phenotypes but only partially alleviated the accelerated HR and constitutive PR
      gene expression phenotypes. The disease resistance phenotype of cpn1-1 suggests
      that the CPN1 gene regulates defense responses. Alternatively, the primary
      function of CPN1 may be the regulation of plant responses to low humidity, and
      the effect of the cpn1-1 mutation on disease resistance may be indirect.

PMID- 11595799
TI  - Endo-beta-1,4-glucanase expression in compatible plant-nematode interactions.
AB  - Cyst nematodes and root-knot nematodes elaborately transform cells within the
      vascular cylinders of plant roots into enlarged, multinucleate, and metabolically
      active feeding cells. The giant cells of root-knot nematodes are formed by
      repeated karyokinesis uncoupled from cytokinesis, whereas the syncytia formed by
      cyst nematodes arise from coordinated cell wall dissolution and the coalescing of
      cell cytoplasm of adjacent cells. Both giant cells and syncytia undergo extensive
      cell wall architectural modifications, including thickening and the formation of
      numerous ingrowths that increase the plasmalemma surface area for solute uptake.
      The origin of enzymes involved in these cell wall modifications has been the
      subject of debate for several decades. Immunolocalization of endo-beta-1,4
      glucanases (EGases) secreted from cyst nematodes was observed in root cortical
      tissue during the intracellular migration of the nematodes, but secretion of cyst
      nematode EGases into developing syncytia was not detected. We have identified
      five EGase genes from tobacco that are upregulated within plant roots upon
      infection by both root-knot and cyst nematodes. In situ localization of tobacco
      EGase transcripts demonstrated that their expression was specifically and
      developmentally upregulated within giant cells, syncytia, root tips, and lateral
      root primordia. These data confirm that cell wall modifications within plant
      parasitic-nematode feeding cells arise from cell wall-modifying enzymes of plant,
      rather than nematode, origin.

PMID- 11595800
TI  - Plastid division is driven by a complex mechanism that involves differential
      transition of the bacterial and eukaryotic division rings.
AB  - During plastid division, two structures have been detected at the division site
      in separate analyses. The plastid-dividing ring can be detected by transmission
      electron microscopy as two (or three) electron-dense rings: an outer ring on the
      cytosolic face of the outer envelope, occasionally a middle ring in the
      intermembrane space, and an inner ring on the stromal face of the inner envelope.
      The FtsZ ring, which plays a central role in bacterial division, also is involved
      in plastid division and is believed to have descended to plastids from
      cyanobacterial endosymbiosis. The relationship between the two structures is not
      known, although there is discussion regarding whether they are identical.
      Biochemical and immunocytochemical investigations, using synchronized
      chloroplasts of the red alga Cyanidioschyzon merolae, showed that the plastid
      FtsZ ring is distinct and separable from the plastid-dividing ring. The FtsZ ring
      localizes in stroma and faces the inner plastid-dividing ring at the far side
      from the inner envelope. The FtsZ ring and the inner and outer plastid-dividing
      rings form in that order before plastid division. The FtsZ ring disappears at the
      late stage of constriction before dissociation of the plastid-dividing ring, when
      the constriction is still in progress. Our results suggest that the FtsZ ring;
      based system, which originated from a plastid ancestor, cyanobacteria, and the
      plastid-dividing ring;-based system, which probably originated from host
      eukaryotic cells, form a complex and are involved in plastid division by distinct
      modes.

PMID- 11595801
TI  - HUA1, a regulator of stamen and carpel identities in Arabidopsis, codes for a
      nuclear RNA binding protein.
AB  - Stamen and carpel identities are specified by the combinatorial activities of
      several floral homeotic genes, APETALA3, PISTILLATA, AGAMOUS (AG), SEPALLATA1
      (SEP1), SEPALLATA2 (SEP2), and SEPALLATA3 (SEP3), all of which code for MADS
      domain DNA binding proteins. AG and the SEP genes also control floral
      determinacy. HUA1 and HUA2 were identified previously as regulators of stamen and
      carpel identities and floral determinacy because the recessive hua1-1 or hua2-1
      allele affected these processes in plants with a lower dosage of functional AG
      (either homozygous for the weak ag-4 allele or heterozygous for the strong ag-1
      allele). HUA2 was cloned previously and shown to code for a novel protein. We
      isolated the HUA1 gene using a map-based approach and show that it encodes a
      protein with six CCCH-type zinc finger motifs that is also found in yeast,
      Caenorhabditis elegans, Drosophila melanogaster, and mammalian proteins. Several
      such genes from invertebrates and mammals are known to play key regulatory roles
      in development. Therefore, HUA1 are another example of non-MADS domain proteins
      involved in organ identity specification. We demonstrated that HUA1 binds
      ribohomopolymers, preferentially poly rU and poly rG, but not double-stranded DNA
      in vitro. This finding suggests that HUA1, like several mammalian CCCH zinc
      finger proteins, is an RNA binding protein. Therefore, HUA1 likely participates
      in a new regulatory mechanism governing flower development.

PMID- 11595802
TI  - Identification and characterization of GONST1, a golgi-localized GDP-mannose
      transporter in Arabidopsis.
AB  - Transport of nucleotide sugars across the Golgi apparatus membrane is required
      for the luminal synthesis of a variety of plant cell surface components. We
      identified an Arabidopsis gene encoding a nucleotide sugar transporter
      (designated GONST1) that we have shown by transient gene expression to be
      localized to the Golgi. GONST1 complemented a GDP-mannose transport-defective
      yeast mutant (vrg4-2), and Golgi-rich vesicles from the complemented strain
      displayed increased GDP-mannose transport activity. GONST1 promoter::beta
      glucuronidase studies suggested that this gene is expressed ubiquitously. The
      identification of a Golgi-localized nucleotide sugar transporter from plants will
      allow the study of the importance of this class of proteins in the synthesis of
      plant cell surface components such as cell wall polysaccharides.

PMID- 11595803
TI  - Genomics analysis of genes expressed in maize endosperm identifies novel seed
      proteins and clarifies patterns of zein gene expression.
AB  - We analyzed cDNA libraries from developing endosperm of the B73 maize inbred line
      to evaluate the expression of storage protein genes. This study showed that zeins
      are by far the most highly expressed genes in the endosperm, but we found an
      inverse relationship between the number of zein genes and the relative amount of
      specific mRNAs. Although alpha-zeins are encoded by large multigene families,
      only a few of these genes are transcribed at high or detectable levels. In
      contrast, relatively small gene families encode the gamma- and delta-zeins, and
      members of these gene families, especially the gamma-zeins, are highly expressed.
      Knowledge of expressed storage protein genes allowed the development of DNA and
      antibody probes that distinguish between closely related gene family members.
      Using in situ hybridization, we found differences in the temporal and spatial
      expression of the alpha-, gamma-, and delta-zein gene families, which provides
      evidence that gamma-zeins are synthesized throughout the endosperm before alpha-
      and delta-zeins. This observation is consistent with earlier studies that
      suggested that gamma-zeins play an important role in prolamin protein body
      assembly. Analysis of endosperm cDNAs also revealed several previously
      unidentified proteins, including a 50-kD gamma-zein, an 18-kD alpha-globulin, and
      a legumin-related protein. Immunolocalization of the 50-kD gamma-zein showed this
      protein to be located at the surface of prolamin-containing protein bodies,
      similar to other gamma-zeins. The 18-kD alpha-globulin, however, is deposited in
      novel, vacuole-like organelles that were not described previously in maize
      endosperm.

PMID- 11595804
TI  - The Arabidopsis TAG1 transposase has an N-terminal zinc finger DNA binding domain
      that recognizes distinct subterminal motifs.
AB  - The in vitro DNA binding activity of the Arabidopsis Tag1 transposase (TAG1) was
      characterized to determine the mechanism of DNA recognition. In addition to
      terminal inverted repeats, the Tag1 element contains four different subterminal
      repeats that flank a transcribed region encoding a 729-amino acid protein. A
      single site-specific DNA binding domain is located near the N terminus of TAG1,
      between residues 21 and 133. This domain binds specifically to the AAACCC and
      TGACCC subterminal repeats, found near the 5' and 3' ends of the element,
      respectively. The ACCC sequence within these repeats is critical for recognition
      because mutations at positions 3, 5, and 6 abolished binding, yet the first two
      bases also are important because substitutions at these positions decreased
      binding by up to 90%. Weak interaction also occurs with the terminal inverted
      repeats, but no binding was observed to the other two 3' subterminal repeat
      regions. Sequence analysis of the TAG1 DNA binding domain revealed a C(2)HC zinc
      finger motif. Tests for metal dependence showed that DNA binding activity was
      inhibited by divalent metal chelators and greatly enhanced by zinc. Furthermore,
      mutation of each cysteine residue predicted to be a metal ligand in the C(2)HC
      motif abolished DNA binding. Together, these data show that the DNA binding
      domain of TAG1 specifically binds to distinct subterminal repeats and contains a
      zinc finger.

PMID- 11595805
TI  - Regulation of circadian methyl benzoate emission in diurnally and nocturnally
      emitting plants.
AB  - Emission of methyl benzoate, one of the most abundant scent compounds of bee
      pollinated snapdragon flowers, occurs in a rhythmic manner, with maximum emission
      during the day, and coincides with the foraging activity of bumblebees. Rhythmic
      emission of methyl benzoate displays a "free-running" cycle in the absence of
      environmental cues (in continuous dark or continuous light), indicating the
      circadian nature of diurnal rhythmicity. Methyl benzoate is produced in upper and
      lower snapdragon petal lobes by enzymatic methylation of benzoic acid in the
      reaction catalyzed by S-adenosyl-L-methionine:benzoic acid carboxyl
      methyltransferase (BAMT). When a detailed time-course analysis of BAMT activity
      in upper and lower petal lobes during a 48-hr period was performed, high BAMT
      activity was found at night as well as in continuous darkness, indicating that
      the BAMT activity is not an oscillation-determining factor. Analysis of the level
      of benzoic acid during a 24-hr period revealed oscillations in the amount of
      benzoic acid during the daily light/dark cycle that were retained in continuous
      darkness. These data clearly show that the total amount of substrate (benzoic
      acid) in the cell is involved in the regulation of the rhythmic emission of
      methyl benzoate. Our results also suggest that similar molecular mechanisms are
      involved in the regulation of methyl benzoate production in diurnally
      (snapdragon) and nocturnally (tobacco and petunia) emitting plants.

PMID- 11595806
TI  - Rapid degradation of auxin/indoleacetic acid proteins requires conserved amino
      acids of domain II and is proteasome dependent.
AB  - Auxin rapidly induces auxin/indoleacetic acid (Aux/IAA) transcription. The
      proteins encoded are short-lived nucleus-localized transcriptional regulators
      that share four conserved domains. In a transient assay measuring protein
      accumulation, an Aux/IAA 13-amino acid domain II consensus sequence was
      sufficient to target firefly luciferase (LUC) for low protein accumulation
      equivalent to that observed previously for full-length PSIAA6. Single amino acid
      substitutions in these 13 amino acids, corresponding to known auxin response
      mutants, resulted in a sixfold to 20-fold increase in protein accumulation.
      Naturally occurring variant amino acids had no effect. Residues identified as
      essential by single alanine substitutions were not sufficient when all flanking
      amino acids were alanine, indicating the importance of flanking regions. Using
      direct protein degradation measurements in transgenic Arabidopsis seedlings, full
      length IAA1, PSIAA6, and the N-terminal 73 PSIAA6 amino acids targeted LUC for
      rapid degradation with 8-min half-lives. The C-terminal 109 amino acids did not
      affect LUC half-life. Smaller regions containing domain II also targeted LUC for
      rapid degradation, but the rates were not equivalent to those of the full-length
      protein. A single domain II substitution in the context of full-length PSIAA6
      increased half-life 30-fold. Proteasome inhibitors affected Aux/IAA::LUC fusion
      protein accumulation, demonstrating the involvement of the proteasome.

PMID- 11595807
TI  - A novel membrane protein that is transported to protein storage vacuoles via
      precursor-accumulating vesicles.
AB  - A novel protein, MP73, was specifically found on the membrane of protein storage
      vacuoles of pumpkin seed. MP73 appeared during seed maturation and disappeared
      rapidly after seed germination, in association with the morphological changes of
      the protein storage vacuoles. The MP73 precursor deduced from the isolated cDNA
      was composed of a signal peptide, a 24-kD domain (P24), and the MP73 domain with
      a putative long alpha-helix of 13 repeats that are rich in glutamic acid and
      arginine residues. Immunocytochemistry and immunoblot analysis showed that the
      precursor-accumulating (PAC) vesicles (endoplasmic reticulum-derived vesicles
      responsible for the transport of storage proteins) accumulated proMP73, but not
      MP73, on the membranes. Subcellular fractionation of the pulse-labeled maturing
      seed demonstrated that the proMP73 form with N-linked oligosaccharides was
      synthesized on the endoplasmic reticulum and then transported to the protein
      storage vacuoles via PAC vesicles. Tunicamycin treatment of the seed resulted in
      the efficient deposition of proMP73 lacking the oligosaccharides (proMP73 Delta
      Psi) into the PAC vesicles but no accumulation of MP73 in vacuoles. Tunicamycin
      might impede the transport of proMP73 Delta Psi from the PAC vesicles to the
      vacuoles or might make the unglycosylated protein unstable in the vacuoles. After
      arrival at protein storage vacuoles, proMP73 was cleaved by the action of a
      vacuolar enzyme to form a 100-kD complex on the vacuolar membranes. These results
      suggest that PAC vesicles might mediate the delivery of not only storage proteins
      but also membrane proteins of the vacuoles.

PMID- 11595809
TI  - Basic Research in Endocrine Dermatology. Proceedings of the 3rd Teupitzer
      Colloquim. Berlin, Germany, September 17-20, 2000.

PMID- 11595808
TI  - A role for initiation codon context in chloroplast translation.
AB  - To study the role of initiation codon context in chloroplast protein synthesis,
      we mutated the three nucleotides immediately upstream of the initiation codon
      (the -1 triplet) of two chloroplast genes in the alga Chlamydomonas reinhardtii.
      In prokaryotes, the -1 triplet has been proposed to base pair with either the 530
      loop of 16S rRNA or the extended anticodon of fMet-tRNA. We found that in vivo,
      none of the chloroplast mutations affected mRNA stability. However, certain
      mutations did cause a temperature-sensitive decrease in translation and a more
      dramatic decrease at room temperature when combined with an AUU initiation codon.
      These mutations disrupt the proposed extended base pairing interaction with the
      fMet-tRNA anticodon loop, suggesting that this interaction may be important in
      vivo. Mutations that would still permit base pairing with the 530 loop of the 16S
      rRNA also had a negative effect on translation, suggesting that this interaction
      does not occur in vivo. Extended base pairing surrounding the initiation codon
      may be part of a mechanism to compensate for the lack of a classic Shine-Dalgarno
      rRNA interaction in the translation of some chloroplast mRNAs.

PMID- 11595810
TI  - Intracrinology and the skin.
AB  - The skin, the largest organ in the human body, is composed of a series of
      androgen-sensitive components that all express the steroidogenic enzymes required
      to transform dehydroepiandrosterone (DHEA) into dihydrotestosterone (DHT). In
      fact, in post-menopausal women, all sex steroids made in the skin are from
      adrenal steroid precursors, especially DHEA. Secretion of this precursor steroid
      by the adrenals decreases progressively from the age of 30 years to less than 50%
      of its maximal value at the age of 60 years. DHEA applied topically or by the
      oral route stimulates sebaceous gland activity, the changes observed being
      completely blocked in the rat by a pure antiandrogen while a pure antiestrogen
      has no significant effect, thus indicating a predominant or almost exclusive
      androgenic effect. In human skin, the enzyme that transforms DHEA into
      androstenedione is type 1 3beta-hydroxysteroid dehydrogenase (type 1 3beta-HSD)
      as revealed by RNase protection and immunocytochemistry. The conversion of
      androstenedione into testosterone is then catalyzed in the human skin by type 5
      17beta-HSD. All the epidermal cells and cells of the sebaceous glands are
      labelled by type 5 17beta-HSD. This enzyme is also present at a high level in the
      hair follicles. Type 1 is the 5alpha-reductase isoform responsible in human skin
      for the conversion of testosterone into DHT. In the vagina, on the other hand,
      DHEA exerts mainly an estrogenic effect, this effect having been demonstrated in
      the rat as well as in post-menopausal women. On the other hand, in experimental
      animals as well as in post-menopausal women, DHEA, at physiological doses, does
      not affect the endometrial epithelium, thus indicating the absence of DHEA
      converting enzymes in this tissue, and avoiding the need for progestins when DHEA
      is used as hormone replacement therapy.

PMID- 11595811
TI  - Human skin: an independent peripheral endocrine organ.
AB  - The historical picture of the endocrine system as a set of discrete hormone
      producing organs has been substituted by organs regarded as organized communities
      in which the cells emit, receive and coordinate molecular signals from
      established endocrine organs, other distant sources, their neighbors, and
      themselves. In this wide sense, the human skin and its tissues are targets as
      well as producers of hormones. Although the role of hormones in the development
      of human skin and its capacity to produce and release hormones are well
      established, little attention has been drawn to the ability of human skin to
      fulfil the requirements of a classic endocrine organ. Indeed, human skin cells
      produce insulin-like growth factors and -binding proteins, propiomelanocortin
      derivatives, catecholamines, steroid hormones and vitamin D from cholesterol,
      retinoids from diet carotenoids, and eicosanoids from fatty acids. Hormones exert
      their biological effects on the skin through interaction with high-affinity
      receptors, such as receptors for peptide hormones, neurotransmitters, steroid
      hormones and thyroid hormones. In addition, the human skin is able to metabolize
      hormones and to activate and inactivate them. These steps are overtaken in most
      cases by different skin cell populations in a coordinated way indicating the
      endocrine autonomy of the skin. Characteristic examples are the metabolic
      pathways of the corticotropin-releasing hormone/propiomelanocortin axis,
      steroidogenesis, vitamin D, and retinoids. Hormones exhibit a wide range of
      biological activities on the skin, with major effects caused by growth
      hormone/insulin-like growth factor-1, neuropeptides, sex steroids,
      glucocorticoids, retinoids, vitamin D, peroxisome proliferator-activated receptor
      ligands, and eicosanoids. At last, human skin produces hormones which are
      released in the circulation and are important for functions of the entire
      organism, such as sex hormones, especially in aged individuals, and insulin-like
      growth factor-binding proteins. Therefore, the human skin fulfils all
      requirements for being the largest, independent peripheral endocrine organ.

PMID- 11595812
TI  - The hair follicle: a paradoxical androgen target organ.
AB  - Androgens are the main regulator of normal human hair growth. After puberty, they
      promote transformation of vellus follicles, producing tiny, unpigmented hairs, to
      terminal ones, forming larger pigmented hairs, in many areas, e.g. the axilla.
      However, they have no apparent effect on the eyelashes, but can cause the
      opposite transformation on the scalp leading to the replacement of terminal hairs
      by vellus ones and the gradual onset of androgenetic alopecia. This paradox
      appears to be an unique hormonal effect. Hair follicles are mainly epithelial
      tissues, continuous with the epidermis, which project into the dermis. A
      mesenchyme-derived dermal papilla enclosed within the hair bulb at the base
      controls many aspects of follicle function. In the current hypothesis for
      androgen regulation, the dermal papilla is also considered the main site of
      androgen action with androgens from the blood binding to receptors in dermal
      papilla cells of androgen-sensitive follicles and causing an alteration of their
      production of paracrine factors for target cells e.g. keratinocytes. Studies of
      cultured dermal papilla cells from sites with different responses to androgens in
      vivo have confirmed the paradoxical responses. All dermal papilla cells from
      androgen-sensitive sites contain low capacity, high affinity androgen receptors.
      However, only some cells formed 5alpha-dihydrotestosterone, e.g. beard but not
      axillary cells, in line with hair growth in 5alpha-reductase deficiency.
      Incubation with androgens also stimulated the mitogenic capacity of beard cell
      media, but inhibited that produced by scalp cells. This suggests that the
      paradoxical differences are due to differential gene expression within hair
      follicles, presumably caused during embryogenesis.

PMID- 11595813
TI  - The SAHA syndrome.
AB  - The presence of seborrhoea, acne, hirsutism and alopecia in women has first been
      summarized as SAHA syndrome in 1982 and can be associated with polycystic ovary
      syndrome, cystic mastitis, obesity and infertility. In 1994, the association of
      these androgen-dependent cutaneous signs, was classified according to their
      etiology into four types: (1) idiopathic, (2) ovarian, (3) adrenal, and (4)
      hyperprolactinemic SAHA. The HAIRAN syndrome has been currently described as a
      fifth variant with polyendocrinopathy. The SAHA syndrome generally occurs in
      young to middle-aged women and involves either the presence of elevated blood
      levels of androgens or increased androgen-driven peripheral response with normal
      circulating androgen levels. Peripheral metabolism of androgens takes place in
      various areas within the pilosebaceous unit, as indicated by local differences in
      the activities of aromatase, 5alpha-reductase as well as of the presence of the
      androgen receptors. In cases of SAHA syndrome, careful diagnostic and clinical
      evaluation has to be performed in order to identify the cause for peripheral
      hyperandrogenism and to exclude androgen-producing tumors. Treatment will target
      the etiology, whereas the management in idiopathic cases will aim to improve the
      clinical features of SAHA.

PMID- 11595814
TI  - Oestrogen receptor beta is not present in the pilosebaceous unit of red deer skin
      during the non-breeding season.
AB  - Androgens and oestrogens both have roles in skin physiology. Recently a second
      oestrogen receptor (ERbeta) has been identified in androgen-dependent tissues.
      The red deer grows a breeding season, androgen-dependent mane when plasma
      testosterone rises; this is replaced with small neck hairs during the non
      breeding season. In non-breeding season deer skin, ERbeta was localised to the
      blood vessels and arrector pili muscle, but in contrast to human skin, not in the
      pilosebaceous unit or epidermis. The androgen receptor was not expressed. Further
      studies with breeding season skin may help to elucidate whether serum androgens
      or androgen receptor expression can modulate the expression of ERbeta in skin.

PMID- 11595815
TI  - Nuclear hormone receptors and mouse skin homeostasis: implication of PPARbeta.
AB  - PPARbeta is expressed in the mouse epidermis during fetal development, and
      progressively disappears from the interfollicular epidermis after birth.
      Interestingly, its expression is strongly reactivated in the adult epidermis in
      conditions where keratinocyte proliferation is induced and during wound healing.
      Data obtained on PPARbeta heterozygous mice reveal that PPARbeta is implicated in
      the control of keratinocyte proliferation and is necessary for rapid healing of a
      skin wound.

PMID- 11595816
TI  - Peroxisome proliferator-activated receptors and skin development.
AB  - PPARs are nuclear hormone receptors. PPAR subtypes (alpha, gamma, delta, the
      latter a xPPARbeta homologue) were initially investigated in skin because of
      their known role in regulating lipid metabolism. Studies adding specific PPAR
      ligand activators to cultured skin or skin cells are compatible with the concepts
      that PPARalpha activation mediates early lipogenic steps common to the function
      of both skin epidermal cells (keratinocytes) and sebaceous cells (sebocytes),
      PPARgamma activation plays a unique role in stimulating sebocyte lipogenesis, and
      PPARdelta activation may contribute to lipid biosynthesis in both sebocytes and
      keratinocytes under certain circumstances. Epidermal keratinocytes appear to
      express small amounts of PPARalpha and PPARdelta mRNA and a trace of PPARgamma
      mRNA which is up-regulated with differentiation. Sebocytes express all subtypes;
      PPARgamma gene expression excedes that in epidermis. The emerging data on PPAR
      protein expression suggests that epidermis normally expresses predominantly
      PPARalpha, while sebocytes express more PPARgamma than PPARalpha. These
      expression patterns may change during hyperplasia, differentiation and
      inflammation. Gene disruption studies in mice are compatible with a contribution
      of PPARalpha to skin barrier function, suggest that PPARgamma is necessary for
      sebocyte differentiation, and indicate that PPARdelta can ameliorate inflammatory
      responses in skin. PPARs appear to play a role in keratinocyte synthesis of the
      lipids that they export to the intercellular space to form the skin permeability
      barrier. They also appear to be important for sebocyte formation of the
      intracellular fused lipid droplets that constitute the holocrine secretion of the
      sebaceous gland. In addition, they may play roles in keratinocyte growth and
      differentiation and the inhibition of skin inflammation by diverse mechanisms not
      necessarily related to fat metabolism.

PMID- 11595817
TI  - Regulation of macrophage gene expression by the peroxisome proliferator-activated
      receptor-gamma.
AB  - The peroxisome proliferator-activated receptor-gamma (PPAR-gamma), which is a
      member of the nuclear hormone receptor superfamily and was originally shown to
      play an important role in adipocyte differentiation and glucose homeostasis, is
      now known to regulate cellular proliferation and inflammatory responses. A range
      of synthetic and naturally occurring substances activates PPAR-gamma, however the
      identities of endogenous ligands for PPAR-gamma and their means of production in
      vivo have not been well established. In monocytes and macrophages, interleukin-4
      (IL-4) increases the expression of 12/15-lipoxygenase and thus 13-HODE and 15
      HETE production. We show that IL-4 induces the expression of PPAR-gamma and
      provide evidence that the coordinate induction of PPAR-gamma and 12/15
      lipoxygenase mediates IL-4 dependent transcription of the CD36 gene and down
      regulation of iNOS in macrophages. These findings suggest that PPAR-gamma
      activity may play an important role in mediating macrophage gene expression
      signaled by IL-4.

PMID- 11595818
TI  - Neuroimmunoregulation of androgens in the adrenal gland and the skin.
AB  - Human adrenals produce large quantities of androgens, especially DHEA which is
      the most abundant circulating hormone in the human body. Adrenal androgens are
      regulated by several factors, including pituitary ACTH and an intricate
      intraadrenal network involving immune cells, cytokines and neuroendocrine
      factors. The skin is a major target of androgens and androgen receptors are
      expressed in the epidermis, dermis, sebaceous glands and hair. In addition, the
      skin has the capacity to metabolize androgens into more powerful compounds.
      Similar to the adrenal gland, there is an intradermal neuro-immune network
      involving the local expression of cytokines and neuropeptides. Dysregulation of
      androgens in the adrenals and/or the skin is associated with acne, hirsutism and
      androgenic alopecia. Therefore, understanding the mechanisms of these intricate
      networks is of both basic and clinical relevance and may help to develop new
      strategies for the treatment of androgen-dependent skin disorders.

PMID- 11595819
TI  - The role of melanocortins in skin homeostasis.
AB  - Melanocortins are structurally related bioactive peptides which are produced by
      many extra-neural tissues including the skin. All of the melanocortins (alpha,
      beta, and gamma-melanocyte-stimulating hormone and adrenocorticotropin) have
      melanotropic activity but can elicit many other effects on skin cells. On the
      basis of in vitro and in vivo findings melanocortins have been shown to regulate
      immune and inflammatory responses, hair growth, exocrine gland activity and
      extracellular matrix composition. These effects are mediated by melanocortin
      receptors among which the melanocortin-1 receptor is most ubiquitously expressed
      by human skin cells. Simultaneous expression of melanocortins and their receptors
      suggest a complex autocrine and/or paracrine regulatory network whose disruption
      invariably affects skin homeostasis. Expression of melanocortin receptors on
      various skin cell types further indicates novel pharmacological targets for the
      treatment of skin diseases.

PMID- 11595820
TI  - Prevalence of endocrine dysfunction in HIV-infected men.
AB  - OBJECTIVE: Endocrine dysfunction is a common problem in patients with human
      immunodeficiency virus infection (HIV). We therefore evaluated the endocrine
      function in 31 male homosexual HIV-1-infected men: mean age 37 +/- 7.2 years
      (range 24-52). METHODS AND MATERIALS: Blood was obtained for baseline T3, T4,
      TSH, LH, FSH, prolactin, testosterone, ACTH and cortisol values. Endocrine
      function tests were performed as TRH, CRH, ACTH, LH-RH and HCG tests. RESULTS:
      Thyroid function: There was a temporarily increased TSH in 3 of 17 patients but
      normal levels for T3, T4 and fT4 (without thyroid antibodies). One patient showed
      signs of latent hyperthyroidism (no response in TRH test). Adrenocortical
      function: Two patients had adrenal insufficiency. They showed a normal baseline
      cortisol level, an elevated ACTH level and no increase in cortisol levels after
      stimulation with CRH. All other patients revealed normal responses on the
      CRH/ACTH tests. Gonadal function: 9 patients had elevated FSH levels (tubular
      insufficiency), 4 patients additionally had increased LH levels
      (hypergonadotropic hypogonadism). 5 patients showed signs of tertiary
      hypogonadism (low LH and testosterone, increase of LH after stimulation with LH
      RH). CONCLUSION: In disorders of thyroid and adrenocortical function of primary
      or tertiary origin, a substitution of hormones should be taken into
      consideration.

PMID- 11595821
TI  - Targeted somatic mutagenesis in mouse epidermis.
AB  - Gene targeting in the mouse is a powerful tool to study mammalian gene function.
      The possibility to efficiently introduce somatic mutations in a given gene, at a
      chosen time and/or in a given cell type will further improve such studies, and
      will facilitate the generation of animal models for human diseases. To create
      targeted somatic mutations in the epidermis, we established transgenic mice
      expressing the bacteriophage P1 Cre recombinase or the tamoxifen-dependent Cre
      ER(T2) recombinase under the control of the human keratin 14 (K14) promoter. We
      show that LoxP flanked (floxed) DNA segments were efficiently excised in
      epidermal keratinocytes of K14-Cre transgenic mice. Furthermore, Tamoxifen
      administration to adult K14-Cre-ER(T2) mice efficiently induced recombination in
      the basal keratinocytes, whereas no background recombination was detected in the
      absence of ligand treatment. These two transgenic lines should be very useful to
      analyse the functional role of a number of genes expressed in keratinocytes.

PMID- 11595822
TI  - Interaction of vitamin D and retinoid receptors on regulation of gene expression.
AB  - Vitamin D and retinoic acid (RA) receptors (VDRs and RARs, respectively), bind as
      heterodimers with the retinoid X receptor (RXR) to hormone response elements
      (HREs) in target genes. In some cases RA and vitamin D can cooperate to stimulate
      transcription through the same HRE. However, VDR/RXR heterodimers bind in a
      transcriptionally unproductive manner and without a defined polarity on certain
      RA response elements, and under these circumstances vitamin D inhibits the
      response to RA. Although competition for binding to DNA may contribute to this
      inhibitory response, titration of common coactivators by VDR also appears to be
      involved in transrepression. Therefore, the transcriptional response to RA and
      vitamin D depends on a complex combinatory pattern of interaction among different
      receptors wih DNA and coactivators.

PMID- 11595823
TI  - Development of efficient transient transfection systems for introducing antisense
      oligonucleotides into human epithelial skin cells.
AB  - Systemic treatment with antisense oligonucleotides is confounded by the dual
      problems of potential cytotoxicity of antisense oligonucleotides and carrier
      molecules such as cationic lipids. Treatment of pathologic conditions affecting
      the skin may avoid these problems to a large degree due to local application. The
      success of antisense strategies has been limited by the poor uptake of the
      transfection reagent and inadequate intracellular compartmentalization. Human
      skin epithelial cells, therefore, are attractive experimental tools for testing
      both in vitro and in vivo antisense therapies. In the present study, we
      determined commercially available liposomes which reproducibly induced a nontoxic
      increase of oligonucleotide uptake in cultured SZ95 sebocytes and keratinocytes.
      The final protocol for SZ95 sebocytes was a 4-hour incubation with DOTAP in a 2:1
      (w/w) lipid/oligonucleotide ratio in serum-free medium. The fluorescein-labeled
      (ATCG)(5) random oligonucleotide molecules were detected within the nucleus. The
      optimum transfection system for primary keratinocytes was poly-L-ornithine (12
      microg/ml) in a medium without bovine pituitary extract over 4 hours. The uptake
      of the oligonucleotide increased in the presence of the polycation and
      oligonucleotide molecules were localized in the cytoplasm of keratinocytes.
      Oligonucleotide transfection with the help of cationic lipids did not affect the
      expression of androgen receptor and of the house-keeping gene beta-actin. Thus,
      cationic lipids are useful for delivery of antisense oligonucleotides into skin
      cells in vitro and may be used for topical application on animal and human skin.

PMID- 11595824
TI  - A novel pathway for hormonally active calcitriol.
AB  - Calcitriol [1alpha,25(OH)2D3], the hormonally active form of vitamin D3 (D3) is
      produced in both renal and extrarenal tissues. Our findings demonstrate that
      physiological doses of UVB radiation at 300 nm induce the conversion of 7
      dehydrocholesterol (7-DHC) via preD3 and D3 into calcitriol in the pmol range in
      epidermal keratinocytes. The hydroxylation of photosynthesized D3 to calcitriol
      is strongly suppressed by ketoconazole, a known inhibitor of cytochrome P450
      mixed function oxidases. The UVB-induced formation of calcitriol in human skin is
      demonstrable in vivo by the microdialysis technique. These results suggest that
      human skin is an autonomous source of hormonally active calcitriol.

PMID- 11595825
TI  - Successful treatment of non-segmental vitiligo: systemic therapy with sex hormone
      thyroid powder mixture.
AB  - We previously reported a patient with generalized vitiligo improved by oral
      administration of the drug for menopausal syndrome (sex hormone-thyroid powder
      mixture). In this study, we reevaluated the efficiency of this drug for vitiligo,
      and examined its pharmacological action in melanogenesis.

PMID- 11595826
TI  - Liposomal ursolic acid (merotaine) increases ceramides and collagen in human
      skin.
AB  - Skin wrinkling and xerosis associated with aging result from decreases of dermal
      collagen and stratum corneum ceramide content. This study demonstrates that
      ursolic acid incorporated into liposomes (Merotaine) increases both the ceramide
      content of cultured normal human epidermal keratinocytes and the collagen content
      of cultured normal human dermal fibroblasts. In clinical tests, Merotaine
      increased the ceramide content in human skin over an 11-day period. Merotaine has
      effects on keratinocyte differentiation and dermal fibroblast collagen synthesis
      similar to retinoids. However, unlike retinoids, Merotaine increases ceramide
      content of human keratinocytes. Ursolic acid may bind to members of the
      glucocorticoid receptor family to initiate changes in keratinocyte gene
      transcription.

PMID- 11595827
TI  - Association of insulin resistance with hyperandrogenia in women.
AB  - In humans, the skin is a target tissue for androgen action; hair growth and sebum
      secretion are under active androgen control. An increased production or
      metabolism of testosterone, the main active androgen, shows up clinically in
      dermatological symptoms such as hirsutism, hyperseborrheic acne and alopecia.
      Polycystic ovary syndrome (PCOS) is the most frequent androgen disorder of
      ovarian function. PCOS patients have amenorrhea or severe oligomenorrhea,
      increased testosterone levels and most often enlarged polycystic ovaries on
      ultrasound examination. In addition, many PCOS patients have a tendency to
      accumulate abdominal fat and/or to develop obesity. Some also display a
      particular metabolic pattern including an atherogenic lipid profile, glucose
      intolerance and an increased fasting insulin level, which is known to be closely
      linked with an insulin resistant state. Several studies have now reported that
      PCOS patients show increased incidence of type 2 diabetes and cardiovascular
      disease. In addition to being a target for androgens the skin has abundant
      insulin receptors on the keratinocyte surface membrane and acanthosis nigricans
      is a common symptom of severe insulin resistance among patients with insulin
      receptor disorders. However, acanthosis nigricans could also be present in PCOS
      women given evidence of the intensity of their insulin resistance. This
      presentation will review the mutual relationship between hyperandrogenia and
      insulin resistance, with particular attention paid to: (1) insulin secretion and
      insulin sensitivity in PCOS; (2) the complexity of the molecular mechanisms
      involved in insulin resistance; (3) the paradoxical relationship between insulin
      resistance and hyperandrogenia; (4) the current genetic studies; and (5) new
      avenues for long-term treatment of PCOS women.

PMID- 11595828
TI  - The molecular basis of androgen insensitivity.
AB  - Androgen action is mediated in the peripheral target cell via the androgen
      receptor (AR). The AR is a nuclear transcription factor, combining a DNA-binding
      and a hormone-binding domain with a large transactivation unit. Androgen
      insensitivity syndrome (AIS) as the clinical entity of defective androgen action
      with variable phenotypes in 46,XY patients is caused by mutations of the X
      chromosomal AR gene. Most variations in the AR gene are point mutations
      inhibiting either hormone or DNA binding. However, even within the same family,
      the phenotype for a given mutation can vary widely. Only few influential factors
      have been identified for the phenotypic diversity. For mutations affecting
      hormone binding, ligand concentration variability during fetal life may be an
      important influence on residual androgen action. A second factor is the
      occurrence of postzygotic de novo mutations, which are present at a high rate in
      single-case families. These somatic mutations lead to expression of both mutant
      and wild-type AR in a single patient and thus allow androgen action despite a
      deleterious mutation of the AR gene. Third, residual androgen response may be
      mediated by additional transcripts of the AR gene which are present in several
      cell types and can be affected in a different pattern by splice-site mutations.
      Whether differential expression of AR-interacting proteins has an influence on
      phenotype has not yet been proven. Moreover, little is known about the regulation
      of AR-dependent genes. Their identification is needed to understand post-AR
      action and, hence, androgenic control of sexual differentiation and maturation.

PMID- 11595829
TI  - Genetics of Peutz-Jeghers syndrome, Carney complex and other familial
      lentiginoses.
AB  - Peutz-Jeghers syndrome (PJS, #175200) and Carney complex (CNC, OMIM#160980) are
      the two most common multiple neoplasia syndromes associated with lentiginosis.
      Both disorders are inherited in an autosomal dominant manner and they have
      recently been elucidated at the molecular level. PJS and CNC share manifestations
      with Cowden syndrome (or Cowden disease) (CS, OMIM#158350) and Bannayan-Riley
      Ruvalcaba syndrome (BRR, OMIM#153480). The endocrine tumors of CS and PJS, which
      could classify these disorders as variant types of multiple endocrine neoplasias
      (MENs), are not present in most CS and BRR patients, but lentigines are shared by
      PJS, CNC and BRR. The serine-threonine kinase STK11 (or LKB1), located on 19p13,
      is mutated in more than half of all PJS kindreds. The R1alpha subunit of c-AMP
      dependent protein kinase A, located on 17q22-24, is mutated in 40% of CNC
      kindreds. The protein phosphatase PTEN is mutated in most cases of CS and in
      almost 50% of BRR kindreds, despite significant clinical heterogeneity in these
      syndromes. The molecular elucidation of the lentiginoses and their related
      syndromes identifies new pathways of growth control and cellular regulation that
      are important for endocrine signaling, tumorigenesis, cutaneous function and
      embryonic development.

PMID- 11595830
TI  - Infiltration of neutrophils following injection of apoptotic cells into the
      peritoneal cavity.
AB  - It has been assumed that apoptosis leads to no production of pro-inflammatory
      cytokines or the production of anti-inflammatory cytokines in vivo, although the
      response of macrophages following phagocytosis of apoptotic cells in vivo has not
      been examined. In this study we therefore examined the response to apoptotic
      cells in vivo. Injection of apoptotic cells into the peritoneal cavity of mice
      led to transient neutrophil infiltration and concomitant production of MIP-2, a
      mouse homologue of IL-8. Apoptotic cells were phagocytosed by macrophages, as
      revealed on two-color flow cytometric analysis and microscopic observation. When
      the mice were depleted of macrophages by pretreatment with liposome-encapsulated
      dichloromethylene bisphosphonate, both neutrophil infiltration and MIP-2
      production were significantly suppressed, suggesting that macrophages are
      required for MIP-2 production in this in vivo response. These results support the
      hypothesis that extensive apoptosis occurring rapidly may induce an inflammatory
      response in vivo.

PMID- 11595831
TI  - Mechanism of apoptosis induced by zinc deficiency in peripheral blood T
      lymphocytes.
AB  - Alterations in intracellular Zn(2+) concentrations are believed to play a crucial
      role in modulating apoptosis. The observation that Zn(2+) deficiency can induce
      cell death both in vivo and in vitro has been attributed to the fact that
      exchange of Zn(2+) for Ca(2+) and Mg(2+) within the nuclei may directly activate
      endogenous endonucleases therefore inducing DNA fragmentation independent of
      cytoplasmic factors. Here we show that the membrane-permeable zinc chelator,
      N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces translocation of
      cytochrome c from the mitochondrial intramembranous space into the cytosol in
      human peripheral blood T lymphocytes (PBL) with subsequent activation of caspases
      3, -8, and -9. Pretreatment of T lymphocytes with caspase inhibitors Z-VAD.fmk or
      DEVD.fmk prevented DNA fragmentation in response to TPEN indicating that
      apoptosis triggered by zinc deficiency is entirely dependent on activation of
      caspase family members. The release of cytochrome c and activation of downstream
      caspases precedes changes in the mitochondrial transmembrane potential (Delta
      Psim). Therefore, cytoplasmic and mitochondrial events are critical to this
      process.

PMID- 11595832
TI  - Mechanisms of Staphylococcus aureus induced apoptosis of human endothelial cells.
AB  - Staphylococcus aureus plays an important role in sepsis, pneumonia and wound
      infections. Here, we demonstrate that infection with several S. aureus strains
      results in apoptosis of human endothelial cells. S. aureus induced an activation
      of cellular caspases, the acid sphingomyelinase, a release of cytochrome c and a
      stimulation of Jun NH2-terminal kinase (JNK). The significance of these findings
      is indicated by a prevention of S. aureus triggered apoptosis of human cells
      deficient for ASM or upon genetic or pharmacological inhibition of JNK or
      caspases, respectively.

PMID- 11595833
TI  - Molecular mechanisms of bacteria induced apoptosis.
AB  - Interaction of mammalian cells with pathogenic bacteria results in a whole
      variety of responses in the infected cells including internalization or
      phagocytosis of the bacterium, release of cytokines, secretion of defensins or
      production of oxygen radicals. However, recent studies pointed out that many
      bacteria are able to trigger apoptosis in the host cell. The induction of
      apoptosis upon infection results from a complex interaction of bacterial proteins
      with cellular proteins finally mediating apoptosis. Thus, bacteria are able to
      activate several pro-apoptotic proteins, e.g. caspases, to inactivate anti
      apoptotic proteins, e.g. NF(kappa)B or MAP-kinases, or to upregulate endogenous
      receptor/ligand systems, that induce apoptosis, on the surface of the infected
      cell. Host cell apoptosis very often serves the bacteria to attack the host and
      to gain access to the tissue. However, in some infections, apoptosis of mammalian
      cells significantly contributes to the host defense against the bacteria further
      indicating the role of apoptosis in host-pathogen interactions.

PMID- 11595834
TI  - p73 in apoptosis.
AB  - The TP53 tumour-suppressor gene belongs to a family that includes the two
      recently identified homologues TP63 and TP73. Overexpression of p73 can activate
      typical p53-responsive genes and induce apoptosis like p53. In addition,
      activation of p73 has been implicated in apoptotic cell death induced by aberrant
      cell proliferation and some forms of DNA-damage. These data together with the
      localization of TP73 on chromosome 1p36, a region frequently deleted in a variety
      of human cancers, led to the hypothesis that p73 has tumour suppressor activity
      just like p53. However, despite its proapoptotic activity in vitro, the lack of
      tumour-formation in p73 knock-out mice and primary human tumour data
      demonstrating overexpression of wild-type p73 currently argue against p73 being a
      classical tumour suppressor. Interestingly, in contrast to TP53, TP73 gives rise
      to a complex pattern of pro- and antiapoptotic p73 isoforms generated by
      differential splicing and alternative promoter usage. Therefore further insight
      into the function and regulation of these structurally and functionally diverse
      p73 proteins is needed to elucidate the role of TP73 for apoptosis and human
      tumorigenesis.

PMID- 11595835
TI  - Synthetic peptides and non-peptidic molecules as probes of structure and function
      of Bcl-2 family proteins and modulators of apoptosis.
AB  - The Bcl-2 family includes a growing number of proteins that play an essential
      role in regulating apoptosis or programmed cell death. Members of this family
      display diverse biological functions and can either inhibit or promote cell death
      signals. Abnormal gene expression of some Bcl-2 family members such as Bcl-2 that
      inhibits apoptosis is found in a wide variety of human cancers and contributes to
      the resistance of tumor cells to conventional therapies through interfering with
      the cell death signals triggered by chemotherapeutic agents. As such, elucidating
      the structure-function and mechanism of the Bcl-2 family is important for
      understanding some of the fundamental principles underlying the death and
      survival of cells and of practical value for developing potential therapeutics to
      control apoptosis in pathological processes. Synthetic peptides derived from
      homologous or heterogeneous domains in Bcl-2 family proteins that might mediate
      different biological activities provide simplified and experimentally more
      tractable models as compared to their full-length counterparts to dissect and
      analyze the complex functional roles of these proteins. Non-peptidic molecules
      identified from random screening of natural products or designed by rational
      structure-based techniques can mimic the effect of synthetic peptides by
      targeting similar active sites on a Bcl-2 family member protein. In this article,
      we review recent progress in using these synthetic peptides and non-peptidic
      mimic molecules to obtain information about the structure and function of Bcl-2
      family proteins and discuss their application in modulating and studying
      intracellular apoptotic signaling.

PMID- 11595836
TI  - Molecular mechanisms of gene expression regulation by the apoptosis-promoting
      protein TIA-1.
AB  - TIA-1 and the related protein TIAR promote DNA fragmentation in digitonin
      permeabilized thymocytes. These proteins contain RNA Recognition Motifs (RRMs)
      and bind uridine-rich sequences. These observations suggested that TIA-1/TIAR are
      pro-apoptotic factors that influence some aspect of RNA metabolism. Here we
      review recent data implicating TIA-1 as a regulator of translation of Tumor
      Necrosis Factor-alpha mRNA and as regulator of alternative splicing of a variety
      of pre-mRNAs, including those of the Fibroblast Growth Factor Receptor 2 and the
      Fas receptor. We also discuss how some of these activities could be integrated in
      the control of programmed of cell death.

PMID- 11595837
TI  - Mechanisms of tamoxifen-induced apoptosis.
AB  - Tamoxifen (TAM) has been used in the treatment of breast cancer for over a
      decade. The observed clinical efficacy of TAM has been attributed to both growth
      arrest and induction of apoptosis within the breast cancer cells. Although the
      primary mechanism of action of TAM is believed to be through the inhibition of
      estrogen receptor (ER), research over the years has indicated that additional,
      non-ER-mediated mechanisms exist. These include modulation of signaling proteins
      such as protein kinase C (PKC), calmodulin, transforming growth factor-beta
      (TGFbeta), and the protooncogene c-myc. Recent studies, including those from our
      laboratory, have implicated the role of caspases and mitogen-activated protein
      kinases (MAPK), including c-Jun N-terminal kinase (JNK) and p38 in TAM-induced
      apoptotic signaling. Oxidative stress, mitochondrial permeability transition
      (MPT), ceramide generation as well as changes in cell membrane fluidity may also
      play important roles in TAM-induced apoptosis. These various signaling pathways
      underlying TAM-induced apoptosis will be reviewed in this article.

PMID- 11595838
TI  - Tissue inhibitors of metalloproteinases and programmed cell death: conundrums,
      controversies and potential implications.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases,
      which can synergistically degrade the major components of extracellular matrix
      (ECM). A key role in maintaining the balance between ECM deposition and
      degradation in several physio-pathological processes is carried out, through
      multiple biological functions, by four members of the tissue inhibitors of
      metalloproteinases (TIMPs) family. TIMP-1 and TIMP-2 are capable of inhibiting
      the activities of MMPs, can inhibit tumour growth, invasion and metastasis,
      exhibit growth factor-like activity, can inhibit angiogenesis and suppress
      programmed cell death (PCD) independently of the MMP-inhibitory activity. TIMP-3
      is the only member which is tightly bound to ECM, inhibits TNF-alpha converting
      enzyme and induces PCD through the stabilization of TNF-alpha receptors on the
      cell surface. TIMP-4 plays a role in ECM homeostasis in a tissue-specific fashion
      and its overexpression induces PCD. The aim of this article is to review the
      exciting and intriguing literature on TIMPs, with special emphasis on their
      conflicting-paradoxical roles in PCD and their potential clinical usefulness.

PMID- 11595839
TI  - Leptomeningeal carcinomatosis and intramedullary spinal cord metastases from lung
      cancer: detection with FDG positron emission tomography.
AB  - A 64-year-old man with a history of large-cell lung carcinoma and recent
      resection of a brain metastasis was examined because of a general decline in his
      ability to function. Whole-body positron emission tomography with fluorine-18
      fluorodeoxyglucose (FDG PET) showed metastases along the spinal cord that were
      confirmed with MRI. Intramedullary spinal cord metastasis occurs rarely, and the
      prognosis is extremely poor. Whole-body FDG PET allows the entire spinal cord to
      be examined noninvasively compared with magnetic resonance imaging, computed
      tomography, and myelography.

PMID- 11595840
TI  - Effect of dietary intake before F-18 FDG positron emission tomographic scanning
      on the evaluation of a solitary pulmonary nodule.
AB  - The uptake of fluorine-18 fluorodeoxyglucose (F-18 FDG) by a malignant tumor
      depends on the blood glucose level. The authors present a striking case that
      illustrates the importance of blood glucose measurement in F-18 FDG positron
      emission tomographic (PET) imaging in a patient with a solitary pulmonary nodule.
      With the emergence of freestanding imaging centers, this case emphasizes the
      importance of using an objective method, such as a glucometer, to measure blood
      glucose levels before F-18 FDG PET imaging. Results of the initial scan were
      equivocal (the patient had eaten before the scan), whereas a hypermetabolic focus
      was clearly identified on a second scan obtained 2 days later.

PMID- 11595841
TI  - Tc-99m-labeled somatostatin receptor-binding peptide imaging for a pulmonary
      nodule.
AB  - A 76-year-old man with chronic obstructive pulmonary disease and a smoking
      history had a 2-cm solitary pulmonary nodule that was likely to be malignant. He
      underwent Tc-99m-labeled somatostatin receptor-binding peptide SPECT. A computed
      tomographic-guided transthoracic needle biopsy performed before the SPECT was
      nondiagnostic. SPECT showed increased uptake of the tracer by the nodule, which
      was subsequently found to be adenocarcinoma by surgical resection.
      Differentiation of malignant from benign nodules by Tc-99m-labeled somatostatin
      imaging may be a reasonable approach in patients at high risk for cancer and
      concurrently at increased risk for complications from invasive diagnostic
      procedures or surgical resection.

PMID- 11595842
TI  - Focal pulmonary uptake during Tc-99m myocardial perfusion SPECT imaging.
AB  - PURPOSE: To evaluate the incidence and origin of abnormal focal pulmonary uptake
      during myocardial perfusion SPECT imaging (MSPECT). METHODS: For evaluation of
      chest pain, 790 men and 581 women (mean age, 56 +/- 13 years) underwent MSPECT.
      All of them received adenosine for pharmacologic stress and Tc-99m tetrofosmin
      (TF, n = 817) or Tc-99m sestamibi (MIBI, n = 554) for myocardial perfusion
      imaging. RESULTS: Review of chest radiography with or without computed tomography
      revealed 111 (8.1%) focal pulmonary diseases. Among them, 38 (34.2%) showed focal
      pulmonary uptake (TF, 22; MIBI, 16); 27 (30.7%) of 88 showed previous pulmonary
      tuberculosis; 2 of 10 (20%) benign pulmonary nodules; 4 of 5 (80%) metastatic
      lung cancers; 2 of 4 (50%) primary lung cancers; and 3 of 4 (75%) pneumonias. No
      difference in uptake was noted for the two imaging agents. Intensity of uptake
      did not vary with origin of the uptake. Focal abnormal pulmonary uptake was found
      in 2.8% of patients undergoing MSPECT and in 34.2% of patients in whom
      radiological examinations showed regional pulmonary disease. In patients with
      abnormal pulmonary uptake on MSPECT, 16% had a malignant lesion, whereas 75% of
      patients with a pulmonary nodule shown on radiography and focal pulmonary uptake
      on MSPECT had a malignant lesion. CONCLUSIONS: Although the incidence of abnormal
      pulmonary uptake during MSPECT was very low, the incidence of malignant lesions
      in the patients with nodular pulmonary uptake was relatively high.

PMID- 11595843
TI  - Reversal of medial compartment osteoarthritic uptake pattern after high tibial
      osteotomy.
AB  - Two cases of osteoarthritis of the knee are presented that illustrate the typical
      medial compartment pattern of scintigraphic uptake. In both cases the patients
      had significant medial joint pain. After high tibial osteotomy, the pattern of
      uptake was altered and paralleled the improvement in symptoms. These observations
      prompt several important issues regarding the cause of the uptake and may provide
      a way to monitor treatment response.

PMID- 11595844
TI  - Rhenium-188 HEDP to treat painful bone metastases.
AB  - PURPOSE: Rhenium-188 hydroxyethylidine diphosphonate (HEDP) is a new and
      attractive radiopharmaceutical that localizes in skeletal metastases and emits
      beta particles that may be therapeutically beneficial. In this study, the
      therapeutic efficacy of Re-188 HEDP was investigated in an uncontrolled initial
      trial of 61 patients with different types of advanced cancer for the palliation
      of painful bone metastases. MATERIALS AND METHODS: Sixty-one patients with
      painful bone metastases of lung, prostate, breast, renal, rhinopharyngeal, and
      bladder cancers were treated with 1.1 GBq (31 mCi) to 6.9 GBq (188 mCi) Re-188
      HEDP. After treatment, the patients were followed at weekly intervals for the
      first 2 months and monthly thereafter for as long as 1 year. Hematologic function
      tests were also performed before and after treatment for 6 weeks. Pain responses
      were scored according to a three-point pain-rating scale as complete,
      significant, and minimal. RESULTS: Prompt and significant relief of bone pain
      occurred in 80% of patients overall. Of the specific tumor types, pain relief was
      achieved in 77% of patients with lung cancer, in 80% with prostate cancer, in 83%
      with breast cancer, in 100% with bladder cancer, in 50% with renal cancer, in 50%
      with rhinopharyngeal cancer, and in 87% of patients with other tumor types, with
      no severe side effects or hematopoietic toxicity. CONCLUSION: This large clinical
      trial verified that Re-188 HEDP is a useful radiopharmaceutical agent to treat
      painful bone metastases from various tumor types.

PMID- 11595845
TI  - Clinical impact of differential renal function to indicate and assess pyeloplasty
      and the significance of coexisting vesicoureteral reflux.
AB  - PURPOSE: In patients with ureteropelvic junction obstruction (JPJO) who are
      conservatively treated, 5% to 10% of them show a deterioration of renal function
      without recovery after delayed pyeloplasty. Should surgery be indicated based on
      observed deterioration of differential renal function (DRF)? Can we expect
      improvement of the DRF after pyeloplasty? What other influencing parameters may
      affect DRF? MATERIALS AND METHODS: In this study, the authors examined 85
      ureterorenal junctions that had undergone the Anderson-Hynes technique for
      surgical correction of UPJO. Based on the values obtained from the preoperative
      DRF (Tc-99m mercaptoacetyltriglycine), the cases were separated into three
      categories: group I had poor DRF (less than 11% of total renal function [TRF]),
      group II had moderate DRF (11% to 33% of TRF), and group III had adequate DRF
      (more than 33% of TRF). Twelve months after surgery, renal function was
      reassessed. The results were correlated with age at surgery, symptoms, coexisting
      vesicoureteral reflux, and drainage. RESULTS: Seven ureterorenal junctions (8%)
      comprised group I, 15 (18%) comprised group II, and 63 (74%) comprised group III.
      After UPJO repair, 13% showed marked improvement in DRF, 86% remained stable, and
      1% exhibited diminished function. In 50% of the renal cases with preoperative DRF
      less than 33%, postoperative improvement was seen. In follow-up renal scans, 30
      cases (35%) revealed nonobstructive drainage, whereas the remaining 53 junctions
      (62%) showed moderate delayed drainage. Both the moderate delayed group (57%) and
      the nonobstructive group (50%) showed similar DRF improvement. Sixty-six percent
      of the patients with impaired DRF improved after pyeloplasty performed within the
      first 3 months of life, compared with 42.8% of patients in whom surgery was
      performed after 5 years of age. Vesicoureteral reflux was evident in 27.2% of the
      patients with preoperative impaired DRF compared with 11% with normal DRF. Forty
      five percent of the patients with impaired DRF and no improvement after surgery
      had coexisting vesicoureteral reflux, compared with 9% of those with
      postoperative improvement. CONCLUSIONS: Sustained renal impairment after
      pyeloplasty is likely as a result of preexisting renal dysplasia with
      vesicoureteral reflux. Moderate delayed drainage after surgery does not affect
      DRF. Surgery for UPJO should be indicated independent of a DRF follow-up (except
      very low DRF) or the age at the time of diagnosis.

PMID- 11595846
TI  - Skull base involvement by a nasopharyngeal carcinoma shown by Tc-99m MDP SPECT
      but not by computed tomography.
AB  - PURPOSE: Plain radiographs, computed tomography (CT), and more recently magnetic
      resonance imaging (MRI) are used routinely to stage carcinoma of the nasopharynx.
      Tc-99m methylene diphosphonate (MDP) SPECT is seldom used for local staging of
      the disease. MATERIALS AND METHODS: Plain radiographs and CT were used to stage
      squamous carcinoma of the nasopharynx in a 50-year-old man with a left XII nerve
      palsy. RESULTS: Findings of the plain radiographs were normal, whereas the CT
      scan revealed a nonhomogenous hyperdense mass in the nasopharynx but intact
      underlying bone. Given the symptoms, a Tc-99m MDP planar scan was ordered and
      showed no enhanced uptake, but SPECT images obtained at the same time revealed
      markedly increased focal radiotracer uptake in the region of the tumor,
      indicating osseous involvement. CONCLUSION: Possible bony invasion with a
      nasopharyngeal carcinoma may be better shown with MDP SPECT than with planar
      isotope bone scans, plain radiographs, or CT.

PMID- 11595847
TI  - Diagnosis of complete ectopic lingual thyroid with Tc-99m pertechnetate
      scintigraphy.
AB  - The authors present four cases of ectopic lingual thyroid disease diagnosed by Tc
      99m pertechnetate scanning, which is an efficient diagnostic tool that yields
      high-quality images in this clinical setting.

PMID- 11595848
TI  - Jejunal diverticular hemorrhage localized by red blood cell scintigraphy.

PMID- 11595849
TI  - Ectopic ureterocele with pyonephrosis: a potential mimic of acute pyelonephritis
      on renal cortical scintigraphy.

PMID- 11595850
TI  - The persistently absent bowel loop: a sign of mass effect on the bowel detected
      by cholescintigraphy.

PMID- 11595851
TI  - Image fusion of magnetic resonance and F-18 FDG positron emission tomography
      using a dual-head camera in coincidence mode to determine the viability of an
      embryonic rhabdomyosarcoma residual mass after proton radiation and chemotherapy.

PMID- 11595852
TI  - Retroperitoneo-bronchial fistula: diagnosis using Tc-99m-labeled colloid.

PMID- 11595853
TI  - Scintigraphy of stress fractures of the sesamoid bones.

PMID- 11595854
TI  - The role of hepatobiliary scintigraphy in the follow-up of benign liver tumors
      secondary to oral contraceptive use.

PMID- 11595855
TI  - Aneurysm of the distal descending thoracic aorta causing a pulmonary perfusion
      defect.

PMID- 11595856
TI  - Giant mediastinal parathyroid adenoma in a woman with hypercalcemia.

PMID- 11595857
TI  - Sarcoidosis with musculocutaneous involvement.

PMID- 11595858
TI  - Perfusion lung scan in lymphangitic carcinomatosis.

PMID- 11595859
TI  - Gastric and colonic bypass grafts: FDG positron emission tomographic patterns.

PMID- 11595860
TI  - Tc-99m hexamethylpropylene amine oxime leukocyte pinhole imaging of the scrotum
      in patients with epididymitis showing equivocal clinical and scintigraphic
      findings.

PMID- 11595861
TI  - Soft tissue uptake observed on Tc-99m MDP bone scans: rare imaging patterns in
      two cases.

PMID- 11595862
TI  - Incidental detection of residual radiation in a transplanted kidney.

PMID- 11595863
TI  - Extensive bone metastases in a patient with prostatic adenocarcinoma and normal
      serum prostate-specific antigen and prostatic acid phosphatase.

PMID- 11595865
TI  - A detective novel read while waiting for an F-18 FDG scan: Broca's area
      activation.

PMID- 11595864
TI  - Ga-67 scan findings in bone marrow involvement with plasmablastic myeloma and
      corresponding Tc-99m MIBI images.

PMID- 11595866
TI  - Paraganglioma seen with FDG dual-head gamma camera coincidence imaging after
      false-negative results of I-123 MIBG imaging.

PMID- 11595867
TI  - Liver regeneration after partial hepatectomy in a patient with hepatoblastoma: Tc
      99m sulfur colloid imaging.

PMID- 11595868
TI  - An unanticipated halo: pericardial effusion diagnosed on a biliary excretion
      study.

PMID- 11595869
TI  - Incidental visualization of pancreatic cancer on Tc-99m MDP bone scan.

PMID- 11595870
TI  - Phimosis revealed by contamination with radioactive urine on bone scintigraphy.

PMID- 11595871
TI  - Visualization of the kidneys on Xe-133 ventilation images of a ventilation
      perfusion scan.

PMID- 11595872
TI  - FDG positron emission tomographic scintigraphy can reveal Castleman's disease as
      a cause of inflammation.

PMID- 11595873
TI  - Flow-function mismatch in unstable angina pectoris demonstrated by gated Tl-201
      SPECT.

PMID- 11595874
TI  - Imaging of angioendothelioma by lymphoscintigraphy.

PMID- 11595875
TI  - Nocardia brain abscess identification with Tl-201 SPECT.

PMID- 11595876
TI  - Unilateral Ga-67 uptake in the hemithorax after recurrence of pleural effusion.

PMID- 11595877
TI  - F-18 FDG pericardial uptake secondary to recent cardiac surgery.

PMID- 11595878
TI  - Increased Tl-201 uptake by a contusion on the left lateral aspect of the face and
      head.

PMID- 11595879
TI  - Prognostic factors in invasive cutaneous malignant melanoma: a population-based
      study and review.
AB  - A population-based study from Sweden identified 711 patients with cutaneous
      malignant melanoma diagnosed in 1965, 1975, 1985 and 1989. Prognostic factors
      were evaluated and a review of the literature was performed. On univariate
      analysis, thick tumours (> 0.8 mm) (odds ratio [OR] 1.8, 95% confidence interval
      [CI] 1.6-2.1), increasing Clark level (OR 1.8, 95% CI 1.6-2.0), ulceration (OR
      1.8, 95% CI 1.6-2.0), nodular melanoma (OR 1.5, 95% CI 1.3-1.6) and increasing
      age (continuous variable, P < 0.0001) were associated with a shorter survival.
      Location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation (OR 0.8, 95% CI
      0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-0.9) were associated with improved
      survival. On multivariate analysis, thick tumours (> 0.8 mm) (OR 1.5, 95% CI 1.2
      1.7) and ulceration (OR 1.4, 95% CI 1.2-1.6) were independently related to a poor
      prognosis, while location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation
      (OR 0.8, 95% CI 0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-1.0) were
      associated with improved survival. No difference in mean tumour thickness was
      seen over time, but there was a significant increase in the percentage of thin
      melanomas (< 0.8 mm) in 1985 (P = 0.01) and 1989 (P = 0.002) compared with 1965.
      The incidence of melanomas with inflammation increased significantly (P = 0.04),
      as did age at diagnosis (P = 0.005).

PMID- 11595880
TI  - CDKN2A novel mutation in a patient from a melanoma-prone family.
AB  - CDKN2A is thought to be the main candidate gene for melanoma susceptibility.
      Deletion or mutations in the CDKN2A gene may produce an imbalance between
      functional p16 and cyclin D, causing abnormal cell growth. We here describe a
      novel mutation consisting of a 1 bp deletion at nucleotide position 201 (codon
      67) (CACGGcGCG) resulting in a truncated protein (stop codon 145). The patient, a
      female subject from a melanoma-prone family, presented at the age of 47 years
      with a superficial spreading melanoma of the trunk. Her father had colon cancer
      at the age of 43 years and melanoma at 63 years, her uncle suffered from gastric
      cancer, and her grandfather had laryngeal cancer.

PMID- 11595881
TI  - Expression profile of genes coding for melanoma differentiation antigens and
      cancer/testis antigens in metastatic lesions of human cutaneous melanoma.
AB  - Vaccination-based therapy of melanoma has so far mainly focused on monovalent
      approaches using either melanoma differentiation antigens or cancer/testis
      antigens. To study the complementarity of expression from these two families of
      antigens recognized by T-cells, we screened 47 metastatic lesions of cutaneous
      melanoma for the expression of three melanoma differentiation antigens and eight
      cancer/testis antigens using reverse transcription-polymerase chain reaction (RT
      PCR). The melanoma differentiation antigens were expressed in a somewhat higher
      percentage of lesions (94% positive for at least one marker) than the
      cancer/testis antigens (91% positive for at least one marker). Nearly all the
      melanoma metastases (98%) expressed at least one of the markers tested. One
      melanoma metastasis was negative for all the markers. Two out of 47 lesions did
      not express any of the three differentiation markers but expressed one or more of
      the cancer/testis antigens, indicating some additional potential for these
      antigens compared with the melanoma differentiation antigens. Therefore, we
      conclude that polyvalent immunotherapy using multiple epitopes from both families
      of antigens might increase the eligibility of melanoma patients and the efficacy
      of the treatment.

PMID- 11595882
TI  - Study of the in vitro cytotoxic potential of natural and synthetic coumarin
      derivatives using human normal and neoplastic skin cell lines.
AB  - A selection of natural and synthetic coumarin compounds, including the
      hydroxylated and nitrated derivatives, were assessed for their cytotoxic
      potential using the microculture 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay for cellular viability. For the first
      time this study utilized both human skin malignant melanocytes (SK-MEL-31) and
      normal human skin fibroblastic cells (HS613.SK), allowing identification of those
      coumarin derivatives that are selectively toxic. Coumarin was found to exhibit
      comparatively low toxicity in both cell types, while 7-hydroxycoumarin (7-OHC)
      and coumarin had similar activity in SK-MEL-31 cells. The entire series of
      hydroxylated coumarins were considerably more toxic in HS613.SK than in SK-MEL-31
      cells. Novel synthetic nitrated coumarins, 6-nitro-7-hydroxycoumarin (6-NO2-7
      OHC) and 3,6,8-nitro-7-hydroxycoumarin (3,6,8-NO2-7-OHC), were shown to be
      significantly more toxic to SK-MEL-31 than HS613.SK cells. In the malignant
      melanocyte skin cell line (SK-MEL-31) the cytotoxic effects of these nitro
      derivatives were shown to be dose and time dependent. Therefore, the cytotoxic
      potential of coumarins appears to be highly dependent on the nature and position
      of the functional group. In addition, nitration of 7-OHC produced compounds that
      were cytotoxic to malignant melanocytes, suggesting that these nitro-derivatives
      may have a chemotherapeutic role in the future.

PMID- 11595883
TI  - Quercetin and tamoxifen sensitize human melanoma cells to hyperthermia.
AB  - Hyperthermia produces regression of human cancer. Because hyperthermia has
      produced only limited results, attention has focused on searching for substances
      able to sensitize tumour cells to the effects of hyperthermia. The flavonoid
      quercetin has been reported to be a hyperthermic sensitizer in ovarian and
      uterine cervical tumours and in leukaemia. Quercetin and tamoxifen inhibit
      melanoma cell growth. We therefore investigated whether quercetin and tamoxifen
      can sensitize M10, M14 and MNT1 human melanoma cells to hyperthermia. We observed
      that both quercetin and tamoxifen synergize with hyperthermia (42.5 degrees C) in
      reducing the clonogenic activity of M14 and MNT1 and in inducing apoptotic cell
      death in all three cell lines. As revealed by flow cytometric and Northern blot
      analyses, quercetin and tamoxifen reduced heat shock protein-70 expression at
      both protein and mRNA levels. Our results suggest that quercetin and tamoxifen
      can be usefully combined with hyperthermia in the therapy of recurrent and/or
      metastatic melanoma.

PMID- 11595884
TI  - Hypercalcaemia of melanoma: incidence, pathogenesis and therapy with
      bisphosphonates.
AB  - Tumour-induced hypercalcaemia (TIH) is a frequent complication of advanced cancer
      but has been rarely reported in patients with malignant melanoma, and its
      pathogenesis remains unexplored. We studied eight patients with TIH and melanoma.
      We determined the incidence and pathogenesis of this complication and the effects
      of bisphosphonate therapy. The incidence of TIH in 751 patients with melanoma was
      1.1%. All patients had liver and bone metastases at the time of hypercalcaemia.
      All patients had osteolytic lesions, most often multiple. The median survival was
      30 days (range 4-136 days). After rehydration, the mean (+/- SEM) corrected
      calcium was 3.42 +/- 0.17 mmol/l. Parathyroid hormone levels were adequately
      suppressed and vitamin D concentrations were normal. Serum osteocalcin, a marker
      of bone formation, was low, except in the two patients with renal insufficiency,
      whereas fasting urinary calcium and hydroxyproline were increased, indicating
      inhibition of bone formation and stimulation of bone resorption. Increased
      parathyroid hormone-related protein secretion was noted in only one patient.
      Three of four patients became normocalcaemic after bisphosphonate therapy for a
      median duration of 2 weeks. In conclusion, hypercalcaemia is a rare complication
      of melanoma. It occurs in the context of far advanced disease and is essentially
      due to aggressive lytic bone metastases with an uncoupling in bone turnover.
      Bisphosphonates can offer short-term palliation.

PMID- 11595885
TI  - Epidemiology of digital epiluminescence microscopy features of acquired
      melanocytic naevi.
AB  - This study addressed the independent association of past and recent sun exposure
      indicators and other host factors with the prevalence of major digital
      epiluminescence microscopy (D-ELM) features such as the pigment network (PN),
      brown globules (BGs), and pigment dots (PDs) in acquired melanocytic naevi. In a
      consecutive series of 189 patients (median age 28 years; range 10-73 years) with
      one or more naevi as diagnosed on D-ELM, we evaluated 35 solitary lesions and one
      naevus randomly selected from each of the 154 patients with multiple lesions. D
      ELM images were classified for the presence or absence of PN, BGs and PDs on two
      blind readings. Data analysis was based on multiple logistic regression. Patient
      age was positively associated with PN and inversely associated with BGs. The
      probability of PN increased with more than 110 days since last exposure to the
      sun, whereas a rapid decrease for BGs and PDs was observed after approximately 1
      month. PDs were significantly more likely among lesions with 6-10 h/day of recent
      exposure. Sex, total lifetime hours of exposure, sunbed use, skin type and colour
      of hair exerted no effect. In conclusion, major D-ELM features appeared to differ
      in their relationship with sun exposure indicators.

PMID- 11595886
TI  - Clinical and dermatoscopic diagnosis of early amelanotic melanoma.
AB  - Amelanotic cutaneous melanoma (ACM) often defies clinical diagnosis because of
      the lack of pigmentation. In an attempt to find diagnostic clues, we
      retrospectively studied the clinical features of 15 thin (< 1 mm thick or Clark
      level I) ACM lesions. The clinical features of early ACMs are identified and
      illustrated to enable early diagnosis and cure of these lesions. The typical
      early lesion presents as an asymmetric macula, which may be uniformly pinkish or
      reddish or, more often, has faint light pigmentation (tan, brown or grey) at the
      periphery; it has borders that may be well- or ill-defined. In our study, these
      features suggested the correct clinical diagnosis in only a minority (40%) of
      cases. Nine cases in this series were also subjected to dermatoscopy. By this
      technique we identified, as constant feature, the presence of small red dots,
      evenly distributed or grouped on a whitish or pink-red background. Our results
      show the importance of dermatoscopy in the evaluation of equivocal pink or
      reddish lesions. Red dots seen with this technique can be an important sign for
      the diagnosis of thin ACM. Since this sign does not appear to be pathognomonic,
      the presence of an associated pigmentary network can be decisive in the
      differential diagnosis.

PMID- 11595887
TI  - Structural asymmetry as a dermatoscopic indicator of malignant melanoma--a latent
      class analysis of sensitivity and classification errors.
AB  - Asymmetry of pigmented skin lesions is an important indicator of possible
      malignant melanoma and contributes substantially to the diagnosis of melanoma in
      the dermatoscopic ABCD rule for melanocytic lesions and other algorithms.
      However, it may be observer dependent. Dermatoscopic asymmetry cannot be assessed
      objectively and no golden standard of asymmetry diagnosis exists. The aim of this
      study was to assess the sensitivity of axis (a-) symmetry using latent class
      analysis. We analysed ratings from four experts in dermatoscopy of 232 pigmented
      lesions by latent class analysis (LCA). Possible ratings were 'no asymmetry',
      'asymmetry in one axis' and 'asymmetry in two axes'. A subset of melanocytic
      lesions (blue naevi excluded) was analysed. Based on LCA, the asymmetry of the
      singular lesion was determined. The sensitivity of 'no asymmetry' was 40-77%, 40
      70% for one-axis asymmetry, and 77-92% for two-axes asymmetry. Overestimation of
      asymmetry was more common than underestimation. Melanomas were significantly more
      asymmetric than pigmented naevi, atypical naevi and papillomas, but not basal
      cell cancers. Analysis of the melanocytic subset gave similar results. The median
      asymmetry of malignant melanomas (1.67, interquartile range 1.81-1.99) was higher
      than for melanocytic naevi. In conclusion, asymmetry and symmetry are important
      criteria for diagnosing or excluding malignant melanoma using the dermatoscopic
      ABCD rule, risk stratification and other diagnostic rules. Using LCA, we
      minimized observer dependence in the assessment of axis (a-) symmetry. LCA,
      besides conceptualizing the diagnostic process, enables the assignment of lesions
      to their true diagnostic class.

PMID- 11595888
TI  - Transscleral laser thermotherapy of hamster Greene melanoma: inducing tumour
      necrosis without scleral damage.
AB  - The feasibility of using transscleral thermotherapy (TSTT) to induce necrosis of
      choroidal melanoma without causing damage to the sclera was investigated. Fifty
      two subcutaneously implanted hamster melanomas covered by human donor sclera were
      irradiated for 1 min with an 810 nm laser using a 3 mm spot diameter, with and
      without cooling of the scleral surface. Immediately after irradiation the
      temperature of the scleral surface was measured with an infrared camera.
      Irradiation at 2000 mW, without cooling of the sclera, resulted in tumour
      necrosis to a mean depth of 4.4 mm and a mean diameter of 5.5 mm, without causing
      damage to the scleral collagen; the surface temperature of the sclera was 44.5
      degrees C, and the estimated temperature at the sclera-tumour interface was 60.1
      degrees C. There was a sharp demarcation between the viable and the necrotic part
      of the tumour. TSTT at 2500 mW, without cooling of the sclera, caused maximal
      tumour necrosis to a mean depth of 5.2 mm and a mean diameter of 5.9 mm; the
      scleral layers adjacent to the tumour had an estimated temperature of 67.6
      degrees C and showed signs of damage in 14% of the experiments. Cooling of the
      sclera resulted in less thermal damage to the sclera but also less tumour
      necrosis. Results indicate that TSTT has potential in the treatment of choroidal
      melanoma.

PMID- 11595889
TI  - Additional cell damage after transpupillary thermotherapy in choroidal malignant
      melanoma.
AB  - The aim of this study was to evaluate the effectiveness of transpupillary
      thermotherapy (TTT) in generating tumour necrosis by light and electron
      microscopy, as well as to evaluate additional cell damage in the area directly
      adherent to the necrotic zone. Four eyes of four patients diagnosed with
      intraocular malignant melanoma of the uvea were treated experimentally with diode
      laser TTT. In all cases a standard technique was used. All eyes were enucleated:
      one eye the day after TTT, two eyes 2 days after TTT, and one eye 6 weeks after
      TTT. Immediately after enucleation the eyes were immersed in standard Karnovsky's
      fixative with cocodylate buffer and prepared for light and electron microscopy.
      In the treated area of all four melanomas we found a dense band of necrotic
      tissue (zone A) consisting of an amorphous mass of dead cells sharply demarcated
      from the rest of the neoplastic tissue. Next to this zone was a more eosinophilic
      and also sharply demarcated band (zone B) that consisted of similar but less
      intensive changes. In the next band (zone C), marked injury to the cellular
      membrane and subcellular structures were seen on electron microscopy. The next
      band (zone D) consisted of changes mainly observed only within the cytoplasm of
      neoplastic cells and significantly less intensive than those in zone C. Outside
      zone D tumour cells that were normal in appearance were seen. No scleral
      alterations induced by heat were found. We concluded that after TTT the cytotoxic
      effect gradually decreases in proportion to the distance from the central point
      of the diode laser spot, with additional cell damage in the area adjacent to the
      necrotic zone. The interval between TTT and enucleation had no influence on the
      histological results.

PMID- 11595890
TI  - Synchronous high-risk melanoma and lymphoid neoplasia.
AB  - Large population-based studies have shown a significant association between
      melanoma and lymphoid neoplasia, particularly non-Hodgkin's lymphoma (NHL) and
      chronic lymphocytic leukaemia (CLL), that is independent of any treatment
      received for the initial tumour. This study examines the presentation, diagnosis,
      treatment and progress of three patients who developed advanced melanoma
      concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate
      their association, discuss common aetiological factors and examine possible
      therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that
      represents the bigger threat to overall survival, initial treatment should be
      targeted towards this cancer. However, because of the interplay between the
      diseases and the possible side-effects of the various treatments, the choice of
      adjuvant therapy requires careful consideration. Immunosuppression associated
      with chemotherapy may permit a more aggressive course for the melanoma, while
      locoregional radiotherapy is contraindicated following lymph node dissections. As
      immunotherapy is of benefit in the treatment of melanoma and has also been
      recently shown to be effective in the management of lymphoid neoplasia, we
      instituted interferon-alpha as adjuvant therapy for these patients, thereby
      utilizing a single agent to treat the dual pathologies. The three patients have
      now been followed-up for 6 months without evidence of disease recurrence or
      progression.

PMID- 11595891
TI  - The systematic relationship between melanomas diagnosed in situ and when
      invasive.
AB  - The Surveillance, Epidemiology and End Results (SEER) Program of the US National
      Cancer Institute has provided population-based, histologically confirmed
      incidence data for melanomas restricted to the epidermis (in situ) and invasive
      melanomas for representative areas of the US for the years 1975 to 1997. The
      incidence of in situ melanomas has increased more rapidly than that for invasive
      melanoma, but both appear to conform to the birth-cohort pattern. As both changed
      from year to year, the incidence of melanoma in situ and invasive melanoma at the
      time of diagnosis were linked by simple proportional relationships. The ratio of
      in situ to invasive tumours was similar in males and females, suggesting that the
      generally better female prognosis develops once the tumour has spread into the
      dermis. Across the age groups, the patients with in situ tumours were older than
      those with invasive tumours. This suggests slower growth, while histological
      confirmation of the diagnoses and the precise linkage between the incidence rates
      for in situ and invasive melanomas implies a close biological connection between
      tumours that progress and those that do not. Study of the in situ tumours could
      reveal what was holding them back.

PMID- 11595892
TI  - Seasonal pattern of the excision rate of melanoma and naevi.
AB  - Based on available information that melanocytic skin lesions presenting a
      junctional component are more susceptible to the influence of ultraviolet
      radiation, this study compares the seasonal differences between the excision
      rates of melanocytic skin lesions with a junctional component to those without.
      The histological diagnoses of 1230 patients with melanocytic skin lesions were
      retrospectively analysed. Depending on the histological diagnosis four groups
      were formed: melanomas, dysplastic naevi, common naevi (junctional and compound
      naevi), and dermal naevi. All dates of operations were allocated to summer or
      winter halves of the year. The collected data were computer analysed for
      statistical description. The number of excisions of melanocytic lesions with a
      junctional component (melanoma, dysplastic naevi, common naevi) showed an
      impressive seasonal variation, with a peak during the summer months, while the
      excision frequency of dermal naevi was approximately constant during the year. In
      conclusion, we suggest that ultraviolet radiation may contribute to the seasonal
      pattern of excision of melanoma and naevi only when a junctional component is
      present.

PMID- 11595893
TI  - A study of infertility treatment and melanoma.
AB  - This study examined the possible association between melanoma and exposure to
      fertility drugs, specifically clomiphene citrate, human menopausal gonadotrophin
      (HMG) and human chorionic gonadotrophin (HCG). A cohort of 3186 women who
      attended a fertility clinic between 1 January 1980 and 31 December 1990 was
      studied; by January 1996, 14 women had been diagnosed with primary melanoma.
      Details of fertility treatment were extracted from the clinical records. The
      incidence of melanoma in the cohort resembled that of the female Queensland
      population (standardized incidence ratio = 0.89, 95% confidence interval [CI] =
      0.54-1.48). Exposure to clomiphene citrate, HMG or HCG did not affect the
      incidence of melanoma. Women with infertile partners who were treated with
      fertility drugs were at increased risk of melanoma (odds ratio [OR] = 3.17, 95%
      CI = 1.01-9.98). Compared with women exposed only to clomiphene citrate and HMG,
      a lower incidence of melanoma was observed among those who received HCG as well
      (OR = 0.10, 95% CI = 0.02-0.42). Women exposed to two or more cycles of either
      clomiphene citrate (OR = 0.27, 95% CI = 0.08-0.94) or HMG (OR = 0.23, 95% CI =
      0.07-0.84) had a significant reduction in melanoma risk compared with women
      exposed to no or one cycle. In summary, a woman's infertility per se was not
      found to be associated with melanoma, while exposure to fertility drugs was
      positively associated with melanoma in women with infertile partners and
      negatively associated in women with low doses of fertility drugs.

PMID- 11595895
TI  - Report on the Eighth World Congress on Cancers of the Skin 18-21 July 2001,
      Zurich, Switzerland.

PMID- 11595894
TI  - MART-1/Melan-A and tyrosinase transcripts in peripheral blood of melanoma
      patients: PCR analyses and follow-up testing in relation to clinical stage and
      disease progression.
AB  - The use of tyrosinase-based polymerase chain reaction (PCR) tests for the
      detection of circulating tumour cells in the blood of melanoma patients has led
      to highly controversial results. We here report on the analysis of 120 blood
      samples from 76 stage I to IV melanoma patients using a new MART-1/Melan-A PCR
      system in conjunction with the tyrosinase-specific assay reported in the
      literature. While there were no positive results in localized disease (stages I
      and II), identification of specific PCR products in stage III melanoma patients
      was restricted to the MART-1/Melan-A tests, with positive results in 11% (two out
      of 19) of the blood specimens analysed. Stage IV melanoma patients presented with
      the highest incidence of detectable mRNA levels, with positive results for
      tyrosinase in 38% (12 out of 32) and for MART-1/Melan-A in 22% (seven out of 32).
      By delineating 64 follow-up specimens covering sampling periods of up to 33
      weeks, stable mRNA expression profiles were identified in nearly 95%. Four
      patients, however, showed PCR changes towards positive MART-1/Melan-A expression
      that were linked to metastatic melanoma progression. Taken together, PCR tests
      for tyrosinase and MART-1/Melan-A seem to lack sufficient detection frequencies
      for the routine monitoring of melanoma disease. Regarding the link between MART
      1/Melan-A seroconversion and the development of metastatic disease, further
      studies are needed to clarify the clinical value of this observation.

PMID- 11595898
TI  - 'Big science' and public trust.

PMID- 11595896
TI  - Helicobacter pylori infection in children.
AB  - A number of scientific breakthroughs since H pylori first became recognized as a
      human pathogen have increased our understanding of the pathogenesis of
      gastroduodenal disease. In particular, advances in molecular bacteriology and the
      complete sequencing of the H pylori genome in 1999, and soon thereafter the human
      genome, provide tools allowing better delineation of the pathogenesis of disease.
      These molecular tools for both bacteria and host should now be applied to
      multicenter pediatric studies that evaluate disease outcome. More recent
      developments indicate that a better understanding of the microbial-host
      interaction is critical to furthering knowledge with respect to H pylori-induced
      diseases. Studies are needed to evaluate either DNA-based or more traditional
      protein-based vaccines, to evaluate more specific antimicrobials that confer
      minimal resistance, and to evaluate probiotics for the management of H pylori
      infection. Multicenter multinational studies of H pylori infection in the
      pediatric population, which include specific, randomized controlled eradication
      trials, are essential to extend current knowledge and develop better predictors
      of disease outcome.

PMID- 11595899
TI  - Bangladesh's poisoned wells.

PMID- 11595901
TI  - Cool atoms make physics prize matter.

PMID- 11595900
TI  - Trio united by division as cell cycle clinches centenary Nobel.

PMID- 11595903
TI  - Illicit GM cotton sparks corporate fury.

PMID- 11595904
TI  - US lays out bare bones of fossil protection package.

PMID- 11595905
TI  - Bangladeshis to sue over arsenic poisoning.

PMID- 11595907
TI  - CERN management faulted over sudden budget crisis.

PMID- 11595908
TI  - Ireland weighs up options to buy into European research.

PMID- 11595910
TI  - Eyes on the prize.

PMID- 11595911
TI  - Public trust requires disclosure of potential conflicts of interest.

PMID- 11595912
TI  - Declaring interests in the fight for good science.

PMID- 11595913
TI  - Financial interests are not the only bias factor.

PMID- 11595914
TI  - Exciting future planned for birthplace of genetics.

PMID- 11595915
TI  - Debate over language's link with intelligence.

PMID- 11595916
TI  - Concerns highlight need to make faster decisions.

PMID- 11595917
TI  - Sound basis for research.

PMID- 11595925
TI  - Science's fiction.

PMID- 11595926
TI  - Unweaving the whirls.

PMID- 11595927
TI  - Semiconductors are cool.

PMID- 11595928
TI  - Global change. Matter of time on the prairie.

PMID- 11595929
TI  - Ion channels. Swimming with sperm.

PMID- 11595931
TI  - Materials science. Melting from within.

PMID- 11595932
TI  - Gene expression. The odd coupling.

PMID- 11595933
TI  - Nanotechnology. Molecules join the assembly line.

PMID- 11595934
TI  - Cloud physics. Inside history on droplets.

PMID- 11595937
TI  - Reward value of attractiveness and gaze.
AB  - Faces are visual objects in our environment that provide strong social cues, with
      the eyes assuming particular importance. Here we show that the perceived
      attractiveness of an unfamiliar face increases brain activity in the ventral
      striatum of the viewer when meeting the person's eye, and decreases activity when
      eye gaze is directed away. Depending on the direction of gaze, attractiveness can
      thus activate dopaminergic regions that are strongly linked to reward prediction,
      indicating that central reward systems may be engaged during the initiation of
      social interactions.

PMID- 11595938
TI  - Oxyphotobacteria. Antenna ring around photosystem I.
AB  - The oceanic picoplankton Prochlorococcus - probably the most abundant
      photosynthetic organism on our planet - can grow at great depths where light
      intensity is very low. We have found that the chlorophyll-binding proteins in a
      deep-living strain of this oxyphotobacterium form a ring around a trimer of the
      photosystem I (PS I) photosynthetic reaction centre, a clever arrangement that
      maximizes the capture of light energy in such dim conditions.

PMID- 11595939
TI  - Catastrophic shifts in ecosystems.
AB  - All ecosystems are exposed to gradual changes in climate, nutrient loading,
      habitat fragmentation or biotic exploitation. Nature is usually assumed to
      respond to gradual change in a smooth way. However, studies on lakes, coral
      reefs, oceans, forests and arid lands have shown that smooth change can be
      interrupted by sudden drastic switches to a contrasting state. Although diverse
      events can trigger such shifts, recent studies show that a loss of resilience
      usually paves the way for a switch to an alternative state. This suggests that
      strategies for sustainable management of such ecosystems should focus on
      maintaining resilience.

PMID- 11595940
TI  - Thin-film thermoelectric devices with high room-temperature figures of merit.
AB  - Thermoelectric materials are of interest for applications as heat pumps and power
      generators. The performance of thermoelectric devices is quantified by a figure
      of merit, ZT, where Z is a measure of a material's thermoelectric properties and
      T is the absolute temperature. A material with a figure of merit of around unity
      was first reported over four decades ago, but since then-despite investigation of
      various approaches-there has been only modest progress in finding materials with
      enhanced ZT values at room temperature. Here we report thin-film thermoelectric
      materials that demonstrate a significant enhancement in ZT at 300 K, compared to
      state-of-the-art bulk Bi2Te3 alloys. This amounts to a maximum observed factor of
      approximately 2.4 for our p-type Bi2Te3/Sb2Te3 superlattice devices. The
      enhancement is achieved by controlling the transport of phonons and electrons in
      the superlattices. Preliminary devices exhibit significant cooling (32 K at
      around room temperature) and the potential to pump a heat flux of up to 700 W cm
      2; the localized cooling and heating occurs some 23,000 times faster than in bulk
      devices. We anticipate that the combination of performance, power density and
      speed achieved in these materials will lead to diverse technological
      applications: for example, in thermochemistry-on-a-chip, DNA microarrays, fibre
      optic switches and microelectrothermal systems.

PMID- 11595942
TI  - Tunable quantum tunnelling of magnetic domain walls.
AB  - Perhaps the most anticipated, yet experimentally elusive, macroscopic quantum
      phenomenon is spin tunnelling in a ferromagnet, which may be formulated in terms
      of domain wall tunnelling. One approach to identifying such a process is to focus
      on mesoscopic systems where the number of domain walls is finite and the motion
      of a single wall has measurable consequences. Research of this type includes
      magnetotransport measurements on thin ferromagnetic wires, and magnetization
      experiments on single particles, nanomagnet ensembles and rare-earth multilayers.
      A second method is to investigate macroscopic disordered ferromagnets, whose
      dynamics are dominated by domain wall motion, and search the associated
      relaxation-time distribution functions for the signature of quantum effects. But
      whereas the classical, thermal processes that operate in these experiments are
      easily regulated via temperature, the quantum processes have so far not been
      tunable, making difficult a definitive interpretation of the results in terms of
      tunnelling. Here we describe a disordered magnetic system for which it is
      possible to adjust the quantum tunnelling probabilities. For this material, we
      can model both the classical, thermally activated response at high temperatures
      and the athermal, tunnelling behaviour at low temperatures within a unified
      framework, where the domain wall is described as a particle with a fixed mass. We
      show that it is possible to tune the quantum tunnelling processes by adjusting
      the 'mass' of this particle with an external magnetic field.

PMID- 11595941
TI  - A sperm ion channel required for sperm motility and male fertility.
AB  - Calcium and cyclic nucleotides have crucial roles in mammalian fertilization, but
      the molecules comprising the Ca2+-permeation pathway in sperm motility are poorly
      understood. Here we describe a putative sperm cation channel, CatSper, whose
      amino-acid sequence most closely resembles a single, six-transmembrane-spanning
      repeat of the voltage-dependent Ca2+-channel four-repeat structure. CatSper is
      located specifically in the principal piece of the sperm tail. Targeted
      disruption of the gene results in male sterility in otherwise normal mice. Sperm
      motility is decreased markedly in CatSper-/- mice, and CatSper-/- sperm are
      unable to fertilize intact eggs. In addition, the cyclic-AMP-induced Ca2+ influx
      is abolished in the sperm of mutant mice. CatSper is thus vital to cAMP-mediated
      Ca2+ influx in sperm, sperm motility and fertilization. CatSper represents an
      excellent target for non-hormonal contraceptives for both men and women.

PMID- 11595943
TI  - Coexistence of superconductivity and ferromagnetism in URhGe.
AB  - The discovery of superconductivity at high pressure (albeit over a restricted
      range) in the ferromagnetic material UGe2 raised the possibility that bulk
      superconductivity might be found in other ferromagnets. The exact symmetry of the
      paired state and the dominant mechanism responsible for the pairing, however,
      remain unidentified. Meanwhile, the conjecture that superconductivity could occur
      more generally in ferromagnets has been fuelled by the recent observation of a
      low-temperature transition that suggests an onset of superconductivity in high
      quality crystals of the itinerant-ferromagnet ZrZn2 (ref. 2), although the
      thermodynamic signature of this transition could not be detected. Here we show
      that the ferromagnet URhGe is superconducting at ambient pressure. In this case,
      we find the thermodynamic signature of the transition-its form is consistent with
      a superconducting pairing of a spin-triplet type, although further testing with
      cleaner samples is needed to confirm this. The combination of superconductivity
      and ferromagnetism may thus be more common and consequently more important than
      hitherto realized.

PMID- 11595944
TI  - Atomic-scale imaging of insulating diamond through resonant electron injection.
AB  - The electronic properties of insulators such as diamond are of interest not only
      for their passive dielectric capabilities for use in electronic devices, but also
      for their strong electron confinement on atomic scales. However, the inherent
      lack of electrical conductivity in insulators usually prevents the investigation
      of their surfaces by atomic-scale characterization techniques such as scanning
      tunnelling microscopy (STM). And although atomic force microscopy could in
      principle be used, imaging diamond surfaces has not yet been possible. Here, we
      demonstrate that STM can be used in an unconventional resonant electron injection
      mode to image insulating diamond surfaces and to probe their electronic
      properties at the atomic scale. Our results reveal striking electronic features
      in high-purity diamond single crystals, such as the existence of one-dimensional
      fully delocalized electronic states and a very long diffusion length for
      conduction-band electrons. We expect that our method can be applied to
      investigate the electronic properties of other insulating materials and so help
      in the design of atomic-scale electronic devices.

PMID- 11595946
TI  - Henry Charles Burdett (1847-1920): outstanding hospital administrator, successful
      Secretary of the Seamen's Hospital Society, and notable philanthropist.

PMID- 11595945
TI  - Asher Asher MD LRCS (Ed.): Victorian physician and medical reformer.

PMID- 11595947
TI  - The enigma of Johnnie "Notions" Williamson.

PMID- 11595948
TI  - Charles Richet and the social role of medical men.

PMID- 11595949
TI  - Charles Thomas Jackson MD, Vesuvius, and the idea of surgical anaesthesia.

PMID- 11595950
TI  - Thomas Henry Huxley (1825-1895).

PMID- 11595951
TI  - Archibald Menzies (1754-1842): a respected surgeon/naturalist.

PMID- 11595952
TI  - Did President Eamon De Valera have a developmental disorder?

PMID- 11595954
TI  - Winston Churchill and M & B.

PMID- 11595953
TI  - Lawrence of Arabia and Hugh Cairns: crash helmets for motorcyclists.

PMID- 11595955
TI  - [Increased incidence of immunoglobulin G antibodies against Helicobacter pylori
      among trainee nurses].
AB  - BACKGROUND AND OBJECTIVE: It is unclear whether persons in the nursing profession
      are at special risk of infection with Helicobacter pylori. If faecal-oral, oral
      oral or gastro-oral transmission occurs, infections with H. pylori should be
      observed after the start of nursing. We studied the incidence of serologically
      proved infections in a collective of trainee nurses. METHODS: The presence of
      immunoglobulin G antibodies against Helicobacter pylori in nurses (128 women, 37
      men, mean age at the beginning of training: 22.2 +/- 5.6 years) was tested at the
      beginning and end of training. RESULTS: At the beginning of training a prevalence
      of 12.5% was found among German nurses (n=152) and of 46.2% among foreign nurses
      (n=13). In the follow up test after a mean of 30 months, eight German nurses had
      new positive results, indicating recent infection. The annual incidence was
      calculated to be 2.3 % and exceeded the expected value for adults not
      occupationally exposed to infectious material. RESULTS: In view of the calculated
      increased incidence, nursing must be considered to be a risk factor for infection
      with Helicobacter pylori.

PMID- 11595956
TI  - [Weil's syndrome with bone marrow involvement after collecting walnuts].
AB  - HISTORY AND CLINICAL FINDINGS: A 65 year-old man was transferred to our
      department from a neighbouring hospital with anuria and epistaxis. A few days
      prior to hospitalization, he had experienced severe muscular and joint pain
      accompanied by chills. A careful history revealed that, in recent weeks, the
      patient had frequently collected wild walnuts growing, for the most part, on the
      banks of a small stream, known to have an infestation of rats. The physical
      examination revealed pronounced jaundice of the skin and sclerae, and petechia on
      the lower legs. INVESTIGATIONS: Laboratory results showed marked
      thrombocytopenia, hyperbilirubinaemia, appreciably elevated urine retention
      parameters and increased C-reactive protein. During the subsequent course of his
      illness, serum leptospiral antibody titres were elevated, indicating an acute
      leptospiral infection manifesting as Weil's syndrome. Silver staining (>>Warthin
      Starry<<) revealed rod-shaped bacteria, presumably representing leptospires, in
      some bone marrow macrophages. TREATMENT AND COURSE: Treatment with i. v.
      penicillin was immediately initiated, and urine output established by intravenous
      fluid resuscitation in the intensive care unit, so that haemodialysis was not
      necessary. The platelet count returned to normal and bilirubin began to decrease
      again. The patient was discharged home after 2 weeks in the hospital. CONCLUSION:
      When a patient presents with the triad of renal failure, jaundice and
      thrombocytpenia in the setting of a possible infection, then the severe form of
      leptospirosis known as Weil inverted question marks syndrome must be considered,
      and antibiotic treatment initiated without delay. Of importance for the
      definitive diagnosis is the repeated determination of the titres of antibodies to
      leptospires in the serum and urine, which usually become positive only in the
      second week of the illness. In our case, we detected bacteria directly in some
      bone marrow macrophages as well.

PMID- 11595957
TI  - [Aphthous esophagitis as an atypical manifestation of a primary HIV-infection].
AB  - HISTORY: A 56-year-old patient from Burkina Faso (Western Africa), living in
      Switzerland for 12 years, was referred to hospital because of acute onset of
      severe painful swallowing. He returned from a 3-week visit to his home country 4
      weeks prior to admission. CLINICAL FINDINGS AND INVESTIGATIONS: Whereas clinical
      and radiological findings were normal, routine laboratory testing showed
      increased parameters of infection. Endoscopy revealed an aphthous esophagitis,
      suggesting a viral infection. Biopsy confirmed an active erosive esophagitis.
      Herpes simplex, cytomegalovirus and candida could not be detected in the biopsy
      specimens (immunohistochemistry, microbiology) and in serum. Both, the anti-HIV
      screening-test and the Western blot antibody test for HIV-1 and HIV-2 were
      negative on admission. Because of the persistent suspicion for an underlying HIV
      Infection, a combined HIV p24-antigen/ antibody-test was performed, showing an
      indeterminate result. Following PCR-based tests for HIV-RNA on days 5 and 12
      showed 86 100 and 103 700 HIV-1 RNA copies/ml plasma, respectively, revealing the
      diagnosis of primary HIV-1 infection. Subsequent serological testing (WB) finally
      documented HIV-1 antibody seroconversion, showing indeterminate and positive
      results on days 5 and 19, respectively. TREATMENT AND COURSE: Within 5 days all
      signs of infection returned to normal and as documented by endoscopy on day 12,
      the esophagitis healed up spontaneously. As the patient intended to go back to
      his home country and the CD4 cell count was 615 x10(6)/l, no antiviral therapy
      was initiated. CONCLUSION: This case report is the first demonstrating an
      atypical symptomatic primary HIV-infection prior to seroconversion, which
      presented itself exclusively as an aphthous esophagitis with no symptoms of the
      classic acute retroviral syndrome. Therefore, each clinical suspicion of an
      underlying HIV-infection should be followed up carefully, even if the patient
      presents with unusual symptoms.

PMID- 11595958
TI  - [Diagnosis of ARDS].

PMID- 11595959
TI  - [Interaction between sildenafil and antihypertensive drugs: what is evidence
      based?].
AB  - Hypertension is an important risk factor for erectile dysfunction (ED).
      Consequently, there is a high coincidence between hypertension and ED. Oral
      sildenafil (Viagra) is an effective treatment for ED in patients with treated or
      untreated hypertension. The most common adverse events of sildenafil (headache,
      flushing, hypotension) result from its moderate vasodilating properties. The
      concomitant use of sildenafil and organic nitrates is contraindicated because it
      may lead to a potentiation of the decreases in blood pressure and thus cause life
      threatening hypotension. In contrast, the concomitant use of sildenafil and
      different classes of antihypertensive agents (beta-blockers, alpha-blockers,
      diuretics, ACE inhibitors, calcium antagonists) may lead to additive but not to
      potentiating blood pressure decreases. Thus, this combination is unlikely to
      cause clinically significant hypotension or an increased incidence of adverse
      events. Sildenafil is an effective and well-tolerated treatment for ED in
      patients taking concomitant antihypertensive medication, including those on
      multidrug regimens.

PMID- 11595960
TI  - [Free choice of doctors: an international comparison and national perspective].

PMID- 11595961
TI  - [Cardiological rehabilitation. And it works!].

PMID- 11595963
TI  - [Epidural spinal cord stimulation in the treatment of therapy-resistant angina
      pectoris].

PMID- 11595964
TI  - Information that orthopedists still need to know and what is missing from the MR
      images of the wrist.
AB  - Magnetic resonance imaging (MRI) has a very established role in imaging many
      pathologic conditions in the wrist. MRI provides useful clinical information
      regarding neoplastic processes. It also provides valuable information in the
      evaluation of tendons and synovium in rheumatoid arthritis. However, it has been
      and is less useful when early ligamentous injuries, including grade I and grade
      II scapholunate and lunotriquetral ligament lesions, are suspected. Also,
      information regarding cartilage injuries and degeneration, especially in wrist
      instabilities, would be more than desirable for treating orthopedists and hand
      surgeons. However, at the current stage, this information is missing, and only
      the more advanced changes are seen in MRI. This article describes and explains
      clinical entities in which that information would help patient care and
      management.

PMID- 11595965
TI  - Magnetic resonance imaging of the wrist.
AB  - Optimal magnetic resonance (MR) imaging of the wrist requires a high field
      strength magnet and a dedicated wrist coil to achieve high-resolution images.
      Using current MR sequences, detailed images of articular cartilage and the
      supporting ligaments and tendons can be obtained. Evaluation of the triangular
      fibrocartilage as well as the extrinsic and intrinsic ligaments of the wrist is
      possible with thin-slice three-dimensional volumetric gradient recalled
      sequences. Fast inversion recovery sequences, used to achieve fat suppression in
      peripheral joints such as the wrist, allow for detection of acute osseous trauma,
      which is often radiographically occult. Cartilage-sensitive imaging allows for
      evaluation of conditions in the skeletally immature patient, such as chronic
      physeal loading in the adolescent gymnast, as well as detection of the sequelae
      of altered biomechanics in the adult, as in the ulnolunate impaction syndrome.
      Moreover, contrast-enhanced magnetic resonance angiography permits a relatively
      noninvasive evaluation of peripheral vascular disease, obviating the need for an
      intraarticular injection.

PMID- 11595966
TI  - High-resolution outpatient imaging of the wrist.
AB  - The authors describe their experience with magnetic resonance imaging (MRI) in
      the evaluation of pathologic conditions of the wrist in an outpatient setting. In
      that setting, because time and quality are both important factors, they have
      concentrated on developing protocols that will allow effective, time-efficient,
      high-resolution MRI of the wrist. With these wrist imaging protocols, they have
      evaluated the majority of commonly encountered pathologic conditions of the
      wrist. They have found that high-resolution images, which can be acquired in a
      very timely fashion when fast spin echo sequences are used in imaging protocols,
      will demonstrate the most common pathologic conditions, including triangular
      fibrocartilage and ligament tears in the wrist. They present the practical issues
      of patient position and imaging sequences as well as the imaging findings in
      those pathologic conditions.

PMID- 11595967
TI  - Wrist MRI and carpal instability: what the surgeon needs to know, and the case
      for dynamic imaging.
AB  - The common clinical problem of carpal instability is often difficult to diagnose
      with the precision necessary to confidently direct appropriate treatment. The
      role of magnetic resonance imaging (MRI) in the evaluation of carpal
      instabilities is evolving but remains problematic. Finding solutions to these
      problems is contingent upon both the imaging specialist and clinician
      appreciating the full scope and clinical implications of the mechanical and
      kinematic complexity inherent in the anatomic design of the carpus. Providing
      specifics about the clinical questions that arise with various carpal
      instabilities serves to highlight the challenges facing current imaging
      technology, and provides a framework that supports the argument for the
      development of dynamic MRI as one--and perhaps the only--truly satisfactory
      solution to this problem.

PMID- 11595968
TI  - Magnetic resonance imaging as a research tool for biomechanical studies of the
      wrist.
AB  - The field of biomechanics has welcomed magnetic resonance imaging (MRI) as a
      research tool to provide quantified anatomy of various body parts in vivo. The
      ability to view, reconstruct, and analyze images of an intact system under
      varying conditions has improved our knowledge of functional anatomy. This article
      forms a review of MRI use in biomechanics research, with examples from several
      areas and an emphasis on the distal upper extremity. Biomechanical parameters
      such as muscle fascicle directions of pull, moment arms in three dimensions,
      muscle cross-sectional areas, and detailed muscle geometry data are prevalent
      because of advances in imaging technology. This has resulted in improved anatomic
      realism in biomechanical models. Wrist biomechanics research has benefited
      greatly using MRI. The unique anatomy of the carpal tunnel, and the concerns
      regarding carpal tunnel syndrome, have prompted numerous studies examining the
      contents of the carpal tunnel, its shape, and its volume. These studies are
      presented, as is an analysis of the finger flexor tendons as they pass through
      the carpal tunnel. These imaging-based studies all examine the aspects of the
      potential mechanisms for median nerve compression at the wrist. MRI is a
      tremendously valuable tool in biomechanics research, especially in the search for
      the mechanisms of carpal tunnel syndrome and wrist function, providing both
      visual representation and quantitative evaluation of anatomic phenomena.

PMID- 11595969
TI  - MRI findings of scapholunate instabilities in coronal images: a short
      communication.
AB  - The plain radiographic findings of scapholunate instabilities are very well
      described in the literature. However, even though the same phenomena that are
      seen in plain radiographs are also seen in magnetic resonance (MR) images, there
      are very few reports in the literature regarding MRI findings in scapholunate
      instabilities. This short communication describes the findings seen in coronal MR
      images in advanced scapholunate instabilities.

PMID- 11595970
TI  - Magnetic resonance imaging of soft tissue changes in rheumatoid arthritis wrist
      joints.
AB  - An increasingly aggressive therapeutic strategy, improved treatment options, and
      encouraging preliminary results have attracted growing attention to the potential
      of magnetic resonance imaging (MRI) in the diagnosis, prognostication, and
      monitoring of rheumatoid arthritis (RA). MRI offers multiplanar imaging with
      unprecedented soft tissue contrast and high spatial resolution. Synovitis, the
      primary joint lesion in RA, can be detected and monitored. By contrast,
      conventional radiography shows only the late signs of preceding synovitis. Other
      soft tissue changes, such as tenosynovitis, tendonitis, enthesitis, joint
      effusions, and ligament and tendon tears, can be visualized. Unfortunately, the
      image resolution in most clinically available MR units is insufficient for
      evaluation of wrist joint cartilage. Preliminary data suggest that MRI is a
      valuable tool in the diagnosis and prognostication of RA. The superior
      sensitivity of MRI may be of major significance in both clinical trials and
      practice. In trials, MRI may allow reductions in the trial size and length
      because of its more sensitive separation of responders from nonresponders. Thus,
      although thorough validation is awaited, particularly concerning the
      reproducibility and prognostic value, MRI seems to be a very promising method for
      assessment of both established and early RA.

PMID- 11595971
TI  - Magnetic resonance imaging of the wrist in rheumatoid arthritis.
AB  - Despite the extraordinary advances made in medical imaging over the past two
      decades and the central role that magnetic resonance imaging (MRI) and other
      sophisticated technologies now play in routine clinical practice, rheumatology
      has benefited relatively little from these advances thus far. Over the past few
      years, however, evidence has accumulated to show that MRI can identify joint
      damage in patients with rheumatoid arthritis earlier and more sensitively than
      other techniques can, and that MRI can directly visualize and monitor changes in
      synovium and bone that precede actual bone erosion. Much of this development is
      being driven by the pharmaceutical and biotechnology industries as they search
      for novel therapies to combat this disease. Accordingly, the imaging tools that
      ultimately will be used to direct patients to specific therapies and then to
      monitor treatment effectiveness and safety are currently being refined and
      validated in rigorous multicenter and multinational clinical trials aimed at
      gaining regulatory approval of these new therapies. As these therapies become
      available for clinical use, radiologists can anticipate increased demand for
      expertise and experience in evaluating disease progression and treatment response
      with these techniques and the emergence of MRI systems specifically adapted for
      this application. The following discussion reviews the current status of this
      development, and points to areas where further advances are anticipated in the
      near future.

PMID- 11595972
TI  - Large-scale deletions and SMADIP1 truncating mutations in syndromic Hirschsprung
      disease with involvement of midline structures.
AB  - Hirschsprung disease (HSCR) is a common malformation of neural-crest-derived
      enteric neurons that is frequently associated with other congenital
      abnormalities. The SMADIP1 gene recently has been recognized as disease causing
      in some patients with 2q22 chromosomal rearrangement, resulting in syndromic HSCR
      with mental retardation, with microcephaly, and with facial dysmorphism. We
      screened 19 patients with HSCR and mental retardation and eventually identified
      large-scale SMADIP1 deletions or truncating mutations in 8 of 19 patients. These
      results allow further delineation of the spectrum of malformations ascribed to
      SMADIP1 haploinsufficiency, which includes frequent features such as hypospadias
      and agenesis of the corpus callosum. Thus, SMADIP1, which encodes a
      transcriptional corepressor of Smad target genes, may play a role not only in the
      patterning of neural-crest-derived cells and of CNS but also in the development
      of midline structures in humans.

PMID- 11595973
TI  - Do the four clades of the mtDNA haplogroup L2 evolve at different rates?
AB  - Forty-seven mtDNAs collected in the Dominican Republic and belonging to the
      African-specific haplogroup L2 were studied by high-resolution RFLP and control
      region sequence analyses. Four sets of diagnostic markers that subdivide L2 into
      four clades (L2a-L2d) were identified, and a survey of published African data
      sets appears to indicate that these clades encompass all L2 mtDNAs and harbor
      very different geographic/ethnic distributions. One mtDNA from each of the four
      clades was completely sequenced by means of a new sequencing protocol that
      minimizes time and expense. The phylogeny of the L2 complete sequences showed
      that the two mtDNAs from L2b and L2d seem disproportionately derived, compared
      with those from L2a and L2c. This result is not consistent with a simple model of
      neutral evolution with a uniform molecular clock. The pattern of nonsynonymous
      versus synonymous substitutions hints at a role for selection in the evolution of
      human mtDNA. Regardless of whether selection is shaping the evolution of modern
      human mtDNAs, the population screening of L2 mtDNAs for the mutations identified
      by our complete sequence study should allow the identification of marker motifs
      of younger age with more restricted geographic distributions, thus providing new
      clues about African prehistory and the origin and relationships of African ethnic
      groups.

PMID- 11595974
TI  - Two episodes of leukoencephalitis associated with recombinant hepatitis B
      vaccination in a single patient.
AB  - Cases of central nervous system demyelination have been reported after
      recombinant hepatitis B vaccination, but no causal link has been clearly
      demonstrated. We present the first case report involving the occurrence of 2
      episodes of leukoencephalitis in a previously healthy patient after vaccination
      and rechallenge with hepatitis B vaccine.

PMID- 11595975
TI  - Viral hemorrhagic fever hazards for travelers in Africa.
AB  - This short review covers 6 viral hemorrhagic fevers (VHFs) that are known to
      occur in Africa: yellow fever, Rift Valley fever, Crimean-Congo hemorrhagic
      fever, Lassa fever, Marburg virus disease, and Ebola hemorrhagic fever. All of
      these have at one time or another affected travelers, often the adventurous kind
      who are "roughing it" in rural areas, who should therefore be made aware by their
      physicians or travel health clinics about their potential risk of exposure to any
      VHF along their travel route and how to minimize the risk. A significant
      proportion of VHF cases involving travelers have affected expatriate health care
      workers who were nosocomially exposed in African hospitals or clinics. The VHFs
      are associated with a high case-fatality rate but are readily prevented by well
      known basic precautions.

PMID- 11595976
TI  - Incidence and risk factors for toxoplasmic encephalitis in human immunodeficiency
      virus-infected patients before and during the highly active antiretroviral
      therapy era.
AB  - The occurrence of toxoplasmic encephalitis (TE) was studied among 19,598 and
      17,016 patients enrolled in the French Hospital Database on human
      immunodeficiency virus whose CD4 cell counts decreased to < or =200x10(6) cells/L
      before (1992-1995) or after (1996-1998) the availability of highly active
      antiretroviral therapy, respectively. The incidence of TE decreased from 3.9
      cases per 100 person-years in the first period (95% confidence interval [CI], 3.7
      4.1) to 1.0 cases per 100 person-years in the second period (95% CI, 0.9-1.1).
      After adjustment for known risk factors for TE, patients who received
      cotrimoxazole prophylaxis had a lower risk of TE (adjusted relative hazard, 0.6
      and 0.5, respectively, for the first and second periods; P < .001). For patients
      treated with cotrimoxazole at inclusion, discontinuation of cotrimoxazole
      increased the risk of TE in both periods (adjusted relative hazard, 4.8 and 4.2,
      respectively; P < .001). Among patients whose CD4 cell counts increased to > 200
      x 10(6) cells/L while undergoing highly active antiretroviral therapy, the
      incidence of TE was 0.1 cases per 100 person-years (95% CI, 0.0-0.2) and was not
      increased by discontinuation of cotrimoxazole.

PMID- 11595977
TI  - Improving efficacy of antifungal therapy by polymerase chain reaction-based
      strategy among febrile patients with neutropenia and cancer.
AB  - Early detection of fungal infections in and corresponding early treatment of
      febrile patients with neutropenia and cancer have been important issues and
      continue to be major challenges for clinicians. The use of nested PCR to make
      therapeutic decisions was studied. Sequential blood samples obtained from 42
      patients with neutropenia and cancer were tested by nested PCR and culture.
      Instead of the empirical antifungal therapy strategy, amphotericin B treatment
      was initiated only for patients who had 2 consecutive positive results by nested
      PCR. A reduced mortality rate was observed for febrile patients with neutropenia
      and cancer who had fungal infections. Thus, this strategy, combined with the
      nested PCR for early detection of fungal infection in febrile patients with
      neutropenia, may be used as a guideline for antifungal therapy.

PMID- 11595978
TI  - Long-term outcome of infective endocarditis: the impact of early surgical
      intervention.
AB  - To determine the impact of early surgical intervention on long-term survival in
      patients with infective endocarditis (IE), charts of all patients who had IE from
      January 1987 through December 1996 were reviewed. A total of 252 patients with
      definite or possible IE were included. Forty-four patients (17.5%) had early
      surgery on median hospital day 2 (range, 0-30 days), and 208 patients (82.5%)
      received medical treatment alone. On multivariate analysis, several variables,
      including early surgical intervention, improved long-term survival rates (hazard
      ratio, 1.5; P=.03), mainly in patients with Staphylococcus aureus etiology
      (P=.04). When patients with prosthetic devices were excluded, the median duration
      of survival for patients who had early surgery was >150 months, compared with
      61.5 months for patients in the medical group (P=.1). Early surgical intervention
      compared with medical therapy alone is associated with increased short- and long
      term survival rates in patients with IE, primarily when IE is caused by S.
      aureus.

PMID- 11595979
TI  - Recurrent bacteremia and multifocal lower limb cellulitis due to Helicobacter
      like organisms in a patient with X-linked hypogammaglobulinemia.
AB  - We describe a 27-year-old man with X-linked (Bruton's) hypogammaglobulinemia who
      presented during a 10-month period with recurrent fevers and multifocal lower
      limb cellulitis associated with bacteremia due to Helicobacter-like organisms
      ("Flexispira rappini" and Helicobacter canis). Susceptible individuals may
      acquire infection of this type as a result of exposure to young dogs.

PMID- 11595980
TI  - Hepatitis C: a hepatologist's approach to an infectious disease.
AB  - The evaluation and management of hepatitis C differ from those of other
      infectious diseases in important ways. In this review, the roles of liver biopsy,
      virus load determination, and genotyping in the pretreatment evaluation and
      monitoring of patients with hepatitis C are discussed from a hepatologist's
      perspective.

PMID- 11595981
TI  - Ethical issues relating to the use of antimicrobial therapy in older adults.
AB  - This article aims to review the literature relating to the ethics of antibiotic
      prescription decisions in older adults and to offer some suggestions as to how
      one might approach these difficult problems. According to many studies, most
      patients and their family members wish to receive antibiotics even when they are
      terminally ill or suffering from advanced dementia. Health care professionals are
      also frequently reluctant to deny the use of antibiotics in such situations. We
      suggest that the difficult decisions regarding whether one should withhold
      treatment can be based on consideration of the ethical principles of autonomy,
      beneficence, nonmaleficence, and justice. From the public health point of view,
      one should also take into account the need to avoid the emergence of
      antimicrobial resistance, keeping in mind the balance between the benefit to the
      specific patient and the cost to future patients. Infectious diseases consultants
      should actively participate in these ethical dilemmas.

PMID- 11595982
TI  - Whither infectious diseases consultations? Analysis of 14,005 consultations from
      a 5-year period.
AB  - During a 5-year period, data from all infectious disease (ID) consultations were
      recorded in a computerized database, which included 9068 new and 4937 additional
      consultations. The purpose of these 14,005 consultations was therapy (for 58%),
      diagnosis (for 13%), both (for 24%), and prophylaxis (for 4%); 51% were performed
      at the bedside, and the remainder were by discussion (19%) or telephone (30%).
      Recommendations included the following: initiation, change, or discontinuation of
      antibiotics (in 46%); performance of diagnostic tests (in 20%) or surgical
      procedures (in 1%); prophylaxis (in 3%); or no change (in 29%). Analysis of new
      versus additional consultations revealed significant differences. A new ID
      consultation was given at a rate of 6.0 consultations per 100 hospitalized
      patients; the rate per department correlated with the expenditure on
      antimicrobials per patient admission. During the study period, expenditure on
      antimicrobials per admission steadily decreased, from $44 in 1995 to $30 in 1999,
      a 35% reduction. In conclusion, analysis of data from ID consultations enables
      the ID service to evaluate its activity and to direct efforts to departments with
      high rates of nosocomial infections, antimicrobial resistance, and/or
      antimicrobial use.

PMID- 11595983
TI  - Bacteremia caused by a Helicobacter pullorum-like organism.
AB  - We report a case of bacteremia caused by a Helicobacter pullorum-like organism in
      a 35-year-old man with pyrexia of unknown origin. Culture of blood samples
      obtained at admission yielded a motile, spiral-shaped gram-negative rod, and 16S
      rRNA gene sequencing identified this organism as Helicobacter pullorum-like,
      showing 23 base differences compared with the recently described "Helicobacter
      canadensis" (a recently proposed group that had previously been classified within
      H. pullorum). We believe that this is the first report of bacteremia caused by
      this organism.

PMID- 11595984
TI  - Glycopeptide resistance among coagulase-negative staphylococci that cause
      bacteremia: epidemiological and clinical findings from a case-control study.
AB  - A 1-year prospective case-control study (ratio of control patients to case
      patients, 3:1) was performed to assess the incidence, risk factors, and genotypic
      patterns of bacteremia caused by glycopeptide-resistant coagulase-negative
      staphylococci (CoNS) and their correlation with hospital glycopeptide use. Among
      535 subjects with CoNS bacteremia, 20 subjects had a glycopeptide-resistant
      strain (19 strains were resistant to teicoplanin and 1 was resistant to both
      teicoplanin and vancomycin). The percentage of resistant isolates recovered in 1
      year was 8% in intensive care units and 3% and 2% in medical and surgical wards,
      respectively. Genotypic analysis of resistant strains showed different patterns
      with a high degree of polymorphism. Use of glycopeptides in individual wards was
      not statistically associated with the percentage of resistance. Previous exposure
      to beta-lactams and glycopeptides, multiple hospitalization in the previous year,
      and concomitant pneumonia were significantly associated with the onset of
      glycopeptide-resistant CoNS bacteremia. Mortality rates were 25% among case
      patients and 18% among control patients, and they were significantly higher among
      patients who presented with concomitant pneumonia and a high Acute Physiology and
      Chronic Health Evaluation III score.

PMID- 11595985
TI  - Prolonged colonization with vancomycin-resistant Enterococcus faecium in long
      term care patients and the significance of "clearance".
AB  - Little is known about the persistence of colonization with vancomycin-resistant
      Enterococcus faecium (VRE) in the nononcologic, non-intensive care unit patient.
      We studied all patients who had VRE isolated on > or =2 occasions of > 1 year
      apart (Study A) and those who had been "cleared" of VRE colonization after 3
      negative stool cultures (Study B). Twelve patients had stored VRE isolates
      recovered > 1 year apart (Study A), and 58% of paired isolates were genotypically
      related according to pulsed field gel electrophoresis patterns. In Study B, stool
      samples were obtained weekly from 21 "cleared" patients for 5 weeks, which
      revealed that 24% were VRE positive. For these culture-positive patients, 72% of
      the cultures failed to detect VRE. Recent antibiotic use was significantly more
      common in the culture-positive patients, as compared with culture-negative
      patients (P=.003). Colonization with VRE may persist for years, even if the
      results of intercurrent surveillance stool and index site cultures are negative.
      Cultures for detection of VRE in stool samples obtained from patients declared
      "cleared" are insensitive.

PMID- 11595986
TI  - Influence of maternal antibodies on neonatal immunization against respiratory
      viruses.
AB  - Vaccines that successfully prevent severe infant respiratory virus diseases
      should induce protection at a very young age because of the low age of patients
      who are hospitalized owing to these viruses. Candidate respiratory virus vaccines
      are being tested in infants who are naive to infection but seropositive to the
      viral agents because they possess maternal IgG antibodies (Abs). Transplacental
      maternal Abs may be partially protective against disease caused by respiratory
      virus infections. Carefully conducted studies have shown that these Abs can also
      profoundly suppress or enhance infant immune responses to immunization. The
      mechanisms underlying regulation of immune responses to viruses by maternal Abs
      are under investigation. This article explores the current knowledge regarding
      the effect of maternal Abs on respiratory virus and measles virus immunization,
      and it reviews the current approaches to overcoming Ab-mediated
      immunosuppression.

PMID- 11595987
TI  - West Nile encephalitis: an emerging disease in the United States.
AB  - In 1999, an epidemic of West Nile virus (WNV) encephalitis occurred in New York
      City (NYC) and 2 surrounding New York counties. Simultaneously, an epizootic
      among American crows and other bird species occurred in 4 states. Indigenous
      transmission of WNV had never been documented in the western hemisphere until
      this epidemic. In 2000, the epizootic expanded to 12 states and the District of
      Columbia, and the epidemic continued in NYC, 5 New Jersey counties, and 1
      Connecticut county. In addition to these outbreaks, several large epidemics of
      WNV have occurred in other regions of the world where this disease was absent or
      rare >5 years ago. Many of the WNV strains isolated during recent outbreaks
      demonstrate an extremely high degree of homology that strongly suggests
      widespread circulation of potentially epidemic strains of WNV. The high rates of
      severe neurologic illness and death among humans, horses, and birds in these
      outbreaks are unprecedented and unexplained. We review the current status of WNV
      in the United States.

PMID- 11595988
TI  - Relapse in persons treated for drug-susceptible tuberculosis in a population with
      high coinfection with human immunodeficiency virus in New York City.
AB  - The optimal duration of tuberculosis treatment for persons infected with human
      immunodeficiency virus (HIV) has been debated. A cohort of 4571 culture-positive
      drug-susceptible patients who received > or =24 weeks of standard 4-drug
      tuberculosis treatment were assessed to determine the incidence of tuberculosis
      relapse. Tuberculosis "recurrence" was defined as having a positive culture < 30
      days after the last treatment date and "relapse" as having a positive culture >
      or =30 days after the last treatment. Patients infected with HIV were more likely
      than those who were uninfected to have recurrence or relapse (2.0 vs. 0.4 per 100
      person-years, P< .001). Patients infected with HIV who received < or =36 weeks of
      treatment were more likely than those who received > 36 weeks to have a
      recurrence (7.9% vs. 1.4%, P< .001). Clinicians should be aware of the
      possibility of recurrence of tuberculosis 6-9 months after the start of
      treatment. Sputum evaluation to ensure cure or assessment 3 months after
      completion of treatment should be performed among persons infected with HIV who
      receive the shorter regimen.

PMID- 11595989
TI  - Rigid nasal endoscopy versus sinus puncture and aspiration for microbiologic
      documentation of acute bacterial maxillary sinusitis.
AB  - Sinus puncture and aspiration is an invasive procedure that hinders patient
      enrollment in studies of acute bacterial maxillary sinusitis (ABMS). Pain and
      minor bleeding also limit its potential diagnostic utility in clinical practice.
      Cultures obtained by rigid nasal endoscopy were compared with those from sinus
      puncture and aspiration in 53 patients with ABMS; 46 patients were assessable.
      Considering recovery of Haemophilus influenzae, Moraxella catarrhalis, or
      Streptococcus pneumoniae from puncture and aspiration as the gold standard,
      endoscopy cultures demonstrated a sensitivity of 85.7% (95% confidence interval,
      56.2-97.5), specificity of 90.6% (73.8-97.5), positive predictive value of 80%
      (51.4-94.7), negative predictive value of 93.5% (77.2-98.9), and accuracy of
      89.1% (75.6-95.9). Ten adverse events related to puncture and aspiration occurred
      in 5 (9.6%) of 52 patients; there were no endoscopy-related adverse events. In
      our study, the largest to date, endoscopic sampling compared favorably with
      puncture and aspiration for identifying H. influenzae, M. catarrhalis, and S.
      pneumoniae in ABMS and produced less morbidity.

PMID- 11595990
TI  - Decreased invasive capacity of quinolone-resistant Escherichia coli in patients
      with urinary tract infections.
AB  - Quinolone-resistant (QR) Escherichia coli may have lower invasive capacity than
      does quinolone-susceptible E. coli. To evaluate this, we prospectively collected
      data regarding all cases of E. coli invasive urinary tract infections (IUTI) in
      669 adults admitted to the Infectious Diseases Unit of our hospital during a 3
      year period, as well as 10,950 patients with cystitis or asymptomatic bacteriuria
      who presented to the outpatient clinic during a 1-year period. QR E. coli was
      isolated in 20% of patients with cystitis, compared with 8% of those with IUTI
      (P<.05). The proportion of E. coli isolates that were quinolone resistant was
      similar in patients with bacteremic and nonbacteremic IUTI. The factors of
      urinary manipulation and structural abnormalities were independently associated
      with the presence of quinolone resistance. Old age was the only variable
      independently associated with blood invasion. QR E. coli is less likely to
      produce invasive disease (pyelonephritis and prostatitis) than is quinolone
      susceptible E. coli. However, once pyelonephritis or prostatitis have developed,
      there is no difference in the incidence of bacteremia.

PMID- 11595991
TI  - Skin indurations in response to tuberculin testing in patients with
      nontuberculous mycobacterial lymphadenitis.
AB  - Mantoux results were examined for 29 children with culture-proven nontuberculous
      mycobacterial lymphadenitis, and 4 species were isolated: Mycobacterium avium
      intracellulare complex (from 14 patients [48%]), Mycobacterium haemophilum (from
      12 [41%]), Mycobacterium simiae (from 2 [7%]), and Mycobacterium scrofulaceum
      (from 1 [3%]); the median indurations for each species were 15.5 mm, 14.5 mm, 20
      mm, and 23 mm, respectively, and in 17 cases (59%), they were > or =15 mm. In
      regions with a low incidence of tuberculosis, lymphadenitis thought to be due to
      nontuberculous mycobacteria should be managed as such, regardless of Mantoux
      results, thereby avoiding antituberculosis treatment.

PMID- 11595992
TI  - Preventing vascular catheter-related infections: current controversies.
AB  - Prevention of vascular catheter-related infection remains an important priority.
      This review focuses on salient controversies regarding optimal preventive
      methods. Intensity of surveillance for nosocomial infections was the single most
      important predictor of prevention in the Study of the Efficacy of Nosocomial
      Infection Control (SENIC). Used suboptimally by most hospitals in the SENIC
      study, surveillance is probably conducted even less today. There has been one
      randomized trial of the optimal method of aseptic insertion for central venous
      catheters and none comparing the 2 most frequently used sites. Scheduled
      replacement did not prevent infection in multiple randomized trials but,
      according to a recent survey, was still being used frequently. Chlorhexidine
      preparation of skin before and during catheterization has significantly reduced
      colonization of catheters in multiple randomized trials and should be used.
      Impregnation of catheter and/or hub surfaces with antiseptics raises less concern
      about fostering the development of antibiotic resistance than does the use of
      antibiotics for this purpose.

PMID- 11595993
TI  - The role of infections in primary hemophagocytic lymphohistiocytosis: a case
      series and review of the literature.
AB  - There is a paucity of literature addressing infection-related morbidity and
      mortality in children with primary hemophagocytic lymphohistiocytosis (HLH), a
      rare condition characterized by abnormal proliferation of macrophages,
      hypercytokinemia, and T cell immunosuppression. Therefore, a retrospective chart
      review was done of patients diagnosed with primary HLH over a 15-year period.
      Significant infections present at diagnosis, during the course of illness, and
      just prior to death or at autopsy were noted. Of the 18 children identified with
      primary HLH, an infectious agent was documented at the initial presentation of
      HLH in 5. Significant infections occurred during therapy in 10 (56%) of 18. Of
      the 12 fatal cases, invasive infection was the cause of death in 8 children, and
      6 of these deaths were directly attributable to invasive fungal infection.
      Significant infections were common during therapy in children with primary HLH,
      and fungal infections were an important cause of mortality in this group.

PMID- 11595994
TI  - Calcified cysticerci provoke perilesional edema and seizures.
AB  - In cases of cysticercosis, seizures and other symptoms occur in persons with only
      calcified brain lesions. The presence of perilesional edema has been documented
      in association with calcified lesions in symptomatic patients, but the frequency
      of this complication and characteristics of the patients who develop it are not
      known. Patients in Peru and the United States with neurocysticercosis, documented
      by positive results of serological testing and with only calcified lesions as
      shown using computerized tomography, were studied using magnetic resonance
      imaging. Perilesional edema was observed in slightly more than one-third of the
      patients, and some patients had frequent, severely disabling episodes. Those with
      an increased proportion of enhancing calcified lesions were more likely to show
      perilesional edema. Edema around calcified lesions is common in this population
      and is associated with seizures and neurological morbidity.

PMID- 11595995
TI  - Understanding the spread of antibiotic resistant pathogens in hospitals:
      mathematical models as tools for control.
AB  - As microorganisms become more resistant to antimicrobial agents, effective
      infection control measures will become increasingly important. However, despite
      multiple studies on infection prevention, few data exist on the quantitative
      effects of the individual aspects of infection control strategies. The
      combination of epidemiologic surveillance, molecular genotyping, observational
      studies on compliance, and mathematical modeling may improve our ability to
      determine the quantitative effects of individual infection control measures. This
      may help to design more effective infection control programs. In this study, we
      review several of the models that have been published and speculate on the
      usefulness of mathematical modeling for improving the prevention of infection.

PMID- 11595997
TI  - In memoriam: Sherwood Washburn, 1911-2000.

PMID- 11595996
TI  - Detection of Mycoplasma pneumoniae DNA in cerebrospinal fluid of a patient with
      M. pneumoniae infection-"associated" stroke.
AB  - A 36-year-old woman presented with an acute ischemic stroke and a concomitant
      Mycoplasma pneumoniae infection that had been proven clinically,
      bacteriologically, and serologically. M. pneumoniae DNA was demonstrated in
      cerebrospinal fluid by positive nested polymerase chain reaction, and intrathecal
      antibody production was also detected. Contrary to previous reports about M.
      pneumoniae-associated stroke, most thrombostatic abnormalities in this patient
      occurred after stroke onset. Although the cause of stroke remains unclear in this
      patient, central nervous system invasion of M. pneumoniae DNA has to be
      considered a possible cause in rare cases of cerebral ischemia.

PMID- 11595998
TI  - New basicrania of Paleocene-Eocene Ignacius: re-evaluation of the Plesiadapiform
      Dermopteran link.
AB  - Plesiadapiformes has long been considered to be an archaic group of Primates.
      Discovery of a paromomyid plesiadapiform skull and independent analysis of
      referred postcrania have led investigators to conclude that Plesiadapiformes
      shares a closer relationship to extant flying lemurs (Dermoptera) than to
      Primates (= Euprimates of Hoffstetter [1977] Bull Mem Soc Anthropol Paris Ser 13
      4:327-346). Despite challenges to this interpretation, the plesiadapiform
      dermopteran relationship has gained currency in recent years. Here we show that
      newly discovered crania of Ignacius graybullianus, preserving previously
      undocumented portions of the ear, are more similar to primates than to
      dermopterans. New specimens confirm that paromomyids lacked the petrosal bulla of
      primates. However, these new specimens also demonstrate that paromomyids likely
      had: 1) a small promontorial branch of the internal carotid artery; 2) a lateral
      route for the internal carotid nerves crossing the promontorium; and 3) a ring
      like ectotympanic with an annular bridge. This pattern is similar to primitive
      primates and fundamentally different from dermopterans, which have: 1) no
      internal carotid artery; 2) internal carotid nerves that take a more medial
      route; and 3) no annular bridge. Recognition of some primate-like traits,
      documented here by new evidence, indicates that Paromomyidae is likely to be more
      closely related to other Paleogene Plesiadapiformes and Eocene Primates than to
      extant Dermoptera. In view of these findings, a link between paromomyids and
      extant dermopterans ("Eudermoptera") is not convincingly supported by a single
      characteristic of the basicranium.

PMID- 11595999
TI  - Enamel hypoplasia in the deciduous teeth of great apes: variation in prevalence
      and timing of defects.
AB  - The prevalence of enamel hypoplasia in the deciduous teeth of great apes has the
      potential to reveal episodes of physiological stress in early stages of
      ontogenetic development. However, little is known about enamel defects of
      deciduous teeth in great apes. Unresolved questions addressed in this study are:
      Do hypoplastic enamel defects occur with equal frequency in different groups of
      great apes? Are enamel hypoplasias more prevalent in the deciduous teeth of male
      or female apes? During what phase of dental development do enamel defects tend to
      form? And, what part of the dental crown is most commonly affected? To answer
      these questions, infant and juvenile skulls of two sympatric genera of great apes
      (Gorilla and Pan) were examined for dental enamel hypoplasias. Specimens from the
      Powell-Cotton Museum (Quex Park, UK; n = 107) are reported here, and compared
      with prior findings based on my examination of juvenile apes at the Cleveland
      Museum of Natural History (Hamman-Todd Collection; n = 100) and Smithsonian
      Institution (National Museum of Natural History; n = 36). All deciduous teeth
      were examined by the author with a x10 hand lens, in oblique incandescent light.
      Defects were classified using Federation Dentaire International (FDI)/Defects of
      Dental Enamel (DDE) standards; defect size and location on the tooth crown were
      measured and marked on dental outline charts. Enamel defects of ape deciduous
      teeth are most common on the labial surface of canine teeth. While deciduous
      incisor and molar teeth consistently exhibit similar defects with prevalences of
      approximately 10%, canines average between 70-75%. Position of enamel defects on
      the canine crown was analyzed by dividing it into three zones (apical, middle,
      and cervical) and calculating defect prevalence by zone. Among gorillas, enamel
      hypoplasia prevalence increases progressively from the apical zone (low) to the
      middle zone to the cervical zone (highest), in both maxillary and mandibular
      canine teeth. Results from all three study collections reveal that among the
      great apes, gorillas (87-92%) and orangutans (91%) have a significantly higher
      prevalence of canine enamel defects than chimpanzees (22-48%). Sex differences in
      canine enamel hypoplasia are small and not statistically significant in any great
      ape. Factors influencing intergroup variation in prevalence of enamel defects and
      their distribution on the canine crown, including physiological stress and
      interspecific dento-gnathic morphological variation, are evaluated.

PMID- 11596000
TI  - Perikymata spacing and distribution on hominid anterior teeth.
AB  - We documented the spacing and distribution of perikymata on the buccal enamel
      surface of fossil hominin anterior teeth with reference to a sample of modern
      human and modern great ape teeth. A sample of 27 anterior teeth attributed to
      Australopithecus (5 to A. afarensis, 22 to A. africanus) and of 33 attributed to
      Paranthropus (6 to P. boisei, and 27 to P. robustus) were replicated and sputter
      coated with gold to enable reflected light microscopy of their surface
      topography. Anterior teeth were then divided into 10 equal divisions of buccal
      crown height. The total perikymata count in each division of crown height was
      recorded using a binocular microscope fitted with a vernier micrometer eyepiece.
      Then the mean number of perikymata per millimeter was calculated for each
      division. Similar comparative data for a modern sample of 115 unworn human
      anterior teeth and 30 African great ape anterior teeth were collected from ground
      sections. Perikymata counts in each taxon (together with either known or presumed
      periodicities of perikymata) were then used to estimate enamel formation times in
      each division of crown height, for all anterior tooth types combined. The
      distributions of these estimates of time taken to form each division of crown
      height follow the same trends as the actual perikymata counts and differ between
      taxa in the same basic way. The distinction between modern African great apes and
      fossil hominins is particularly clear. Finally, we calculated crown formation
      times for each anterior tooth type by summing cuspal and lateral enamel formation
      times. Estimates of average crown formation times in australopiths are shorter
      than those calculated for both modern human and African great ape anterior teeth.
      The data presented here provide a better basis for exploring differences in
      perikymata spacing and distribution among fossil hominins, and provide the first
      opportunity to describe four specimens attributed to Homo in this context.
      Preliminary data indicate that differences may exist among the species attributed
      to early Homo, especially between Homo ergaster and Homo rudolfensis on the one
      hand, and Homo habilis sensu strico on the other.

PMID- 11596001
TI  - Case of metastatic carcinoma from end of the 8th-early 9th century Slovakia.
AB  - The first case of metastatic carcinoma ever detected in Slovakia comes from a
      Slavonic cemetery at Borovce, in the district of Piest'any, which is dated from
      the end of the 8th to the middle of the 12th century AD. The disease afflicted a
      50-60-year-old male, buried in a grave from the older phase of inhumation (8th
      early 9th century AD). A number of osteolytic metastases were found in all bones
      of the skull and postcranial skeleton except for the forearms, hands, lower legs,
      and feet. They were studied macroscopically by standard X-rays, and by scanning
      electron microscopy and laser scanning confocal microscopy. Analogous finds from
      Central European countries were also obtained. They are discussed in relation to
      their chronology, which shows a tendency of increasing occurrence culminating in
      the Middle Ages. Some demographic and paleopathological characteristics of the
      burials in the Borovce cemetery are also provided.

PMID- 11596002
TI  - Founding Amerindian mitochondrial DNA lineages in ancient Maya from Xcaret,
      Quintana Roo.
AB  - Ancient DNA from the bone remains of 25 out of 28 pre-Columbian individuals from
      the Late Classic-Postclassic Maya site of Xcaret, Quintana Roo, was recovered,
      and mitochondrial DNA (mtDNA) was amplified by using the polymerase chain
      reaction. The presence of the four founding Amerindian mtDNA lineages was
      investigated by restriction analysis and by direct sequencing in selected
      individuals. The mtDNA lineages A, B, and C were found in this population. Eighty
      four percent of the individuals were lineage A, whereas lineages B and C were
      present at low frequencies, 4% and 8%, respectively. Lineage D was absent from
      our sample. One individual did not possess any of the four lineages. Six
      skeletons out of 7 dated from the Late Classic period were haplotype A, whereas
      11 skeletons out of 16 dated from the Postclassic period were also haplotype A.
      The distribution of mtDNA lineages in the Xcaret population contrasts sharply
      with that found in ancient Maya from Copan, which lack lineages A and B. On the
      other hand, our results resemble more closely the frequencies of mtDNA lineages
      found in contemporary Maya from the Yucatan Peninsula and in other Native
      American contemporary populations of Mesoamerican origin.

PMID- 11596003
TI  - Potential seasonal ecological challenge of heat strain among Australian
      Aboriginal people practicing traditional subsistence methods: a computer
      simulation.
AB  - It has been largely accepted that Australian Aboriginal people practicing hunting
      and gathering traditionally underused their objective economic possibilities by
      working short hours relative to nonhunter-gatherer populations. However, the
      possibility that their subsistence quest might have been limited by potential
      heat strain has not been considered for Australian hunter-gatherers. In this
      article the influence of work and heat load on the potential for heat strain
      among adult male Australian Aboriginal people is modelled. The possibility that
      the short working day of Arnhem Land adults reported in the literature might
      reflect ecologically limited work scheduling by way of potential heat strain is
      examined. Three climatic regions of the North of Western Australia and the
      Northern Territory were identified, using data available from the Australian
      Bureau of Meteorology. Data from the months of January, April, July, and October
      were used with the United States Army Heat Strain Model, along with assumptions
      with respect to work load and time scheduling. Predictive modelling indicates
      that a late start to the working day could carry considerable risks of potential
      heat strain during the summer, when humidity and maximum daily temperature are
      highest for all three climatic regions, but especially in the tropical coastal
      region. While extended work times may have been needed to acquire adequate food
      under traditional conditions, work output could have been limited by potential
      heat strain under some conditions likely to have prevailed.

PMID- 11596004
TI  - Simple method for developing percentile growth curves for height and weight.
AB  - The present paper demonstrates the ease of use of method I by Preece and Baine
      ([1978] Ann Hum Biol 5:1-24) in generating smoothed growth curves for both height
      and weight. Using the National Center for Health Statistics (NCHS) growth curve
      data, smoothed curves were developed and compared to those produced using the
      least-squares-cubic-spline method. Based on the lower sum of squares and better
      fit of shape as indicated by residual examination, it was concluded that the
      method I curve fitting procedure by Preece and Baine ([1978] Ann Hum Biol 5:1-24)
      fit centile growth curves for height and weight in 2-18-year-old male and female
      children as well as, if not better than, the least-squares-cubic-spline method
      used in developing the 1979 NCHS growth curves. Further, as this paper
      demonstrates, smoothed curves can be generated on a desktop computer using
      readily available software (the SOLVER function within Microsoft EXCEL).

PMID- 11596005
TI  - Lymphocytes in the bronchoalveolar space reenter the lung tissue by means of the
      alveolar epithelium, migrate to regional lymph nodes, and subsequently rejoin the
      systemic immune system.
AB  - Lymphocytes in the bronchoalveolar space are routinely obtained and examined in
      lung diseases such as asthma or sarcoidosis. In a pig model, labeled lymphocytes
      were found in regional lymph nodes after intrabronchial instillation, indicating
      that reentry of lymphocytes from the bronchoalveolar space into the body is
      possible. In the present study, the route and kinetics of the reentry of
      bronchoalveolar lymphocytes were investigated in a congenic rat model using
      immunohistochemistry on cryostat and semithin sections and confocal laser
      scanning microscopy. As early as 15 min after intratracheal instillation
      lymphocytes were found to leave the bronchoalveolar space by transmigration
      through alveolar but not bronchial epithelium and were observed in interstitial
      alveolar tissue. At 6 hr after intratracheal instillation, T and B lymphocytes
      appeared in the draining lymph nodes of the lung with an increase after 24 and 48
      hr. The kinetic pattern clearly differed in nondraining lymph nodes and other
      organs. After 6 hr, only single cells were found in nondraining lymph nodes,
      spleen, and blood with a slight increase after 24 hr, and only occasionally were
      single cells seen in the liver, thymus, or Peyer's patches 24 and 48 hr after
      instillation. In conclusion, T and B lymphocytes can leave the alveolar space by
      reentry into the lung tissue through alveolar epithelium. They reach regional
      lymph nodes by means of lymphatic vessels and are then distributed all over the
      body to rejoin the systemic immune system. Coming into contact with environmental
      antigens, these lymphocytes could perform an important function in the lung
      immune system and might be a target for inhalative therapy.

PMID- 11596006
TI  - Developmental regulation of connexin 43 expression in fetal mouse testicular
      cells.
AB  - Multiple connexins have been identified in testicular cells. Several lines of
      evidences indicate that, among them, connexin 43 (Cx43) may be unique for control
      of gonad development and spermatogenesis. To date, however, it is not known
      whether Cx43 is expressed in the fetal testis and what possible types of cellular
      interactions mediated by this connexin are critical to male fertility. In the
      present work, expression of Cx43 was investigated at various developmental ages
      in cryosections from mouse testis by using specific antibodies against Cx43. In
      serial or double-labeled sections, Cx43 localization was compared with
      immunocytochemical distribution of steroidogenic enzyme, 3beta-hydroxysteroid
      dehydrogenase (3betaHSD), Mullerian inhibitory hormone (MIH), and germinal
      nuclear cell antigen (GCNA1), which are specific markers, respectively, of
      interstitial Leydig, Sertoli, and germinal cells. Sections were analyzed by
      fluorescence microscopy. We found that Cx43 immunofluorescence (IF) was uniformly
      distributed in the undifferentiated gonad at 11.5 days post coitus (dpc) and in
      cells of the mesonephric tubules. In the undifferentiated gonad, Cx43 was
      localized between primordial germ cells and somatic cells. At 12.5 dpc, when the
      gonad has undergone sexual differentiation, in the interstitium Cx43 was
      localized in Leydig cells and in the seminiferous cord it was localized between
      adjacent Sertoli cells. In Leydig and Sertoli cells, Cx43 labeling increased at
      14.5, 16.5, and 18.5 dpc. From day 12.5 up to 18.5 dpc, Cx43 was also localized
      in cell borders between germinal and Sertoli cells. In conclusion, this study
      demonstrates that from the earliest stages of gonadal development, Cx43 is
      expressed in the principal cell types that participate in the control of male
      fertility. It also shows that Cx43 expression in Leydig and Sertoli cells
      increase during fetal life. Finally, it provides evidence that, throughout
      embryonic life, Cx43 forms gap junctions between Sertoli and germinal cells.

PMID- 11596007
TI  - Posterior maxillary (PM) plane and anterior cranial architecture in primates.
AB  - This study tests several hypotheses of integration between the cranial base and
      face in primates. After reviewing the definition and anatomical basis for the
      posterior maxillary (PM) plane, which demarcates the back of the midface at its
      junction with the sphenoid, we demonstrate how the PM plane can be identified
      accurately on radiographs, and confirm that it maintains a 90 degrees angle
      relative to the Neutral Horizontal Axis of the orbits in all primates. In
      addition, we use the PM plane to test Dabelow's (1929) hypothesis that the orbits
      and anterior cranial base are more highly integrated in anthropoids than in
      strepsirrhines, and we test the hypothesis that the midline anterior cranial base
      (planum sphenoideum) and anterior cranial floor (planum sphenoideum plus
      cribriform plate) in primates are highly correlated with each other relative to
      the PM plane. The mean angle between the anterior cranial base and the PM plane
      does not differ significantly from 90 degrees in anthropoids, but differs
      significantly in strepsirrhines. The anterior cranial base and anterior cranial
      floor, however, correlate well with each other relative to the PM plane in both
      suborders of primates, independent of orbital orientation and configuration. The
      PM plane, anterior cranial base, and anterior cranial floor, therefore, form an
      integrated structural complex, a "facial block," whose orientation relative to
      the posterior cranial base influences craniofacial shape among anthropoids in
      which orbital orientation influences the orientation of the anterior cranial
      base. One such effect is that increases in cranial base flexion shorten the
      antero-posterior length of the nasopharynx.

PMID- 11596008
TI  - Cell proliferation and differentiation in a model of human skin equivalent.
AB  - Recent advances in culturing technology has permitted the production of
      organotypic models that may be referred to as human skin equivalents (HSE). We
      have studied histochemical, ultrastructural, and kinetic aspects of an HSE
      composed by an epidermal equivalent and a dermal equivalent separated by a
      basement membrane. Only keratinocytes and fibroblasts were present in the
      epidermal and dermal equivalents, respectively; cells of other lineages were
      lacking. Keratinocyte stratification and differentiation seemed similar to
      natural skin. Evidence is shown that such an HSE may also release growth factors
      such as vascular endothelial growth factor that are believed to play a role in
      skin grafting. The distribution of cycling cells as well as the values of the
      growth fraction are comparable to those observed in natural skin. Although the
      absence of several cells populations that reside in natural skin is a remarkable
      feature of this HSE, the high levels of tissue organization and cell
      differentiation lead us to believe that such an HSE may be considered a candidate
      substitute of human skin in biological, pharmacologic, and clinical applications.

PMID- 11596009
TI  - Septation and valvar formation in the outflow tract of the embryonic chick heart.
AB  - There is no agreement, in the chick, about the number of the endocardial cushions
      within the outflow tract or their pattern of fusion. Also, little is known of
      their relative contributions to the formation of the arterial valves, the
      subpulmonary infundibulum, and the arterial valvar sinuses. As the chick heart is
      an important model for studying septation of the outflow tract, our objective was
      to clarify these issues. Normal septation of the outflow tract was studied in a
      series of 60 staged chick hearts, by using stained whole-mount preparations,
      serial sections, and scanning electron microscopy. A further six hearts were
      examined subsequent to hatching. At stage 21, two pairs of endocardial cushions
      were seen within the developing outflow tract. One pair was positioned
      proximally, with the other pair located distally. By stage 25, a third distal
      cushion had developed. This finding was before the appearance of two further,
      intercalated, endocardial cushions, also distally positioned, which were first
      seen at stage 29. In the arterial segment, the aortic and pulmonary channels were
      separated by the structure known as the aortopulmonary septum. The dorsal limb of
      this septum penetrated the distal dorsal cushion, whereas the ventral limb grew
      between the remaining two distal cushions, both of which were positioned
      ventrally. The three distal endocardial cushions, and the two intercalated
      endocardial cushions, contributed to the formation of the leaflets and sinuses of
      the arterial roots. The two proximal cushions gave rise to a transient septum,
      which later became transformed into the muscular component of the subpulmonary
      infundibulum. Concomitant with these changes, an extracardiac tissue plane was
      formed which separated this newly formed structure from the sinuses of the aortic
      root. Our study confirms that three endocardial cushions are positioned distally,
      and two proximally, within the developing outflow tract of the chick. The pattern
      of the distal cushions, and the position of the ventral limb of the
      aortopulmonary septum, differs significantly from that seen in mammals.

PMID- 11596010
TI  - Limb myosin heavy chain isoproteins and muscle fiber types in the adult goat
      (Capra hircus).
AB  - The primary focus of this study was the accurate classification of limb skeletal
      muscle fiber types in adult goats (Capra hircus) according to the myosin heavy
      chain (MHC) isoform they express. Combined methodologies of gel electrophoresis,
      immunoblotting, immunohistochemistry, myofibrillar ATPase (mATPase), and
      quantitative metabolic enzyme histochemistry of M. semitendinosus samples were
      developed. Three MHCs were identified and tentatively designated as types I, IIA,
      and IIX. Five fiber types were defined immunohistochemically according to their
      MHC content: I, I+IIA, IIA, IIAX, and IIX. The hybrid fast-twitch fibers (IIAX)
      totaled 21% of the fiber population analyzed. The three major pure fibers (I,
      IIA, and IIX) could be objectively separated upon the basis of their mATPase
      activities after acid and alkaline preincubations. The prominent number of hybrid
      fibers, however, could not be delineated with these mATPase methods. Metabolic
      and size properties of muscle fibers varied according to their MHC content, but
      overlapped the full range of muscle fiber phenotypes. These integrated data
      demonstrate that type II skeletal muscle fibers of small ruminants have been
      misclassified in previous studies. The immunohistochemical approach developed in
      the present study offers new prospects for muscle fiber typing in caprine
      experimental studies and meat production technologies.

PMID- 11596011
TI  - Basement membrane of mouse bone marrow sinusoids shows distinctive structure and
      proteoglycan composition: a high resolution ultrastructural study.
AB  - Venous sinusoids in bone marrow are the site of a large-scale traffic of cells
      between the extravascular hemopoietic compartment and the blood stream. The wall
      of the sinusoids consists solely of a basement membrane interposed between a
      layer of endothelial cells and an incomplete covering of adventitial cells. To
      examine its possible structural specialization, the basement membrane of bone
      marrow sinusoids has now been examined by high resolution electron microscopy of
      perfusion-fixed mouse bone marrow. The basement membrane layer was discontinuous,
      consisting of irregular masses of amorphous material within a uniform 60-nm-wide
      space between apposing endothelial cells and adventitial cell processes. At
      maximal magnifications, the material was resolved as a random arrangement of
      components lacking the "cord network" formation seen in basement membranes
      elsewhere. Individual components exhibited distinctive ultrastructural features
      whose molecular identity has previously been established. By these morphological
      criteria, the basement membrane contained unusually abundant chondroitin sulfate
      proteoglycan (CSPG) revealed by 3-nm-wide "double tracks," and moderate amounts
      of both laminin as dense irregular coils and type IV collagen as 1-1.5-nm-wide
      filaments, together with less conspicuous amounts of amyloid P forming pentagonal
      frames. In contrast, 4.5-5-nm-wide "double tracks" characteristic of heparan
      sulfate proteoglycan (HSPG) were absent. The findings demonstrate that, in
      comparison with "typical" basement membranes in other tissues, the bone marrow
      sinusoidal basement membrane is uniquely specialized in several respects. Its
      discontinuous nature, lack of network organization, and absence of HSPG, a
      molecule that normally helps to maintain membrane integrity, may facilitate
      disassembly and reassembly of basement membrane material in concert with
      movements of adventitial cell processes as maturing hemopoietic cells pass
      through the sinusoidal wall: the exceptionally large quantity of CSPG may
      represent a reservoir of CD44 receptor for use in hemopoiesis.

PMID- 11596012
TI  - Immunolocalization of vacuolar-type H+-ATPase, cathepsin K, matrix
      metalloproteinase-9, and receptor activator of NFkappaB ligand in odontoclasts
      during physiological root resorption of human deciduous teeth.
AB  - To investigate the cellular mechanisms of physiological root resorption in human
      deciduous teeth, the authors examined the immunocytochemical localization of
      vacuolar-type H+-ATPase, a lysosomal cysteine proteinase, cathepsin K, matrix
      metalloproteinase-9 (MMP-9), and receptor activator of NFKB ligand (RANKL) in
      odontoclasts. H+-ATPase, cathepsin K, and MMP-9 are the most important enzymes
      for decalcification of apatite crystals and degradation of type-I collagen. In
      addition, RANKL is one of the key regulatory molecules in osteoclast formation
      and functions. Odontoclasts developed extensive ruffled borders and clear zones
      apposed to the resorbing root dentine surfaces. On immunoelectron microscopy, the
      expression of vacuolar-type H+-ATPase was detected along the limiting membranes
      of pale vacuoles and the ruffled border membranes of odontoclasts. Cathepsin K in
      odontoclasts was localized within pale vacuoles, lysosomes, the extracellular
      canals of ruffled borders, and the underlying resorbing dentine surfaces. MMP-9
      localization in odontoclasts was similar to those of cathepsin K. RANKL was
      detected in both mononuclear stromal cells and odontoclasts located on resorbing
      dentine surfaces. These results suggest that (1) odontoclasts are directly
      involved in decalcification of apatite crystals by active extrusion of proton
      ions mediated by H+-ATPase and (2) extracellular degradation of dentine type-I
      collagen by both cathepsin K and MMP-9, and (3) odontoclast differentiation and
      activity are regulated, at least in part, by RANKL, possibly produced by
      mononuclear stromal cells and odontoclasts themselves in the resorbing tissues.
      Thus, the cellular mechanisms of physiological root resorption appear to be quite
      similar to those of osteoclastic bone resorption.

PMID- 11596013
TI  - High-dose chemotherapy in high-risk myelodysplastic syndrome: covariate-adjusted
      comparison of five regimens.
AB  - BACKGROUND: Antileukemic chemotherapy has been used for two decades to treat high
      risk myelodysplastic syndrome (refractory anemia with excess of blasts [RAEB] and
      RAEB in transformation into acute leukemia [RAEB-t]) patients. Because the
      results of standard regimens have been disappointing, high-dose chemotherapeutic
      regimens were investigated recently. In the absence of randomized trials, the
      relative merits of various treatment regimens are unknown. METHODS: The authors
      analyzed the outcome for 394 newly diagnosed patients treated between 1991 and
      1999 with five regimens consisting of intermediate- or high-dose cytosine
      arabinoside (A) in combination with idarubicin (I), and introduced
      cyclophosphamide (C) and the new agents fludarabine (F) and topotecan (T) into
      new combinations with A. In addition to defining the role of high-intensity
      chemotherapy in the overall outcome for patients with RAEB-t and RAEB, the
      authors determined the relative merits of the five regimens (IA, FA, FAI, TA, and
      CAT), accounting for the nonrandom distribution of the prognostic covariates.
      RESULTS: The overall complete response (CR) rate of 58% was significantly
      associated with karyotype, performance status (PS), treatment in the laminar air
      flow room, duration of antecedent hematologic disorder and age, but not French
      American-British or International Prognostic Scoring System risk categories.
      Multivariate analysis did not identify statistically significant differences in
      CR rates obtained with each regimen. Induction death rates increased with age
      with all but the TA regimen; they were lowest with TA (5.4%) and highest with FAI
      (20.7%), and these differences were significant in patients older than 65 years.
      The trend for time to death was the same as for time to recurrence in all groups.
      Multivariate analysis of time to death identified treatment regimen (FA, FAI, and
      CAT), cytogenetic status (-5/-7), increasing age, and PS greater than 2 as
      significant independent unfavorable prognostic factors. After prognostic
      variables were accounted for, survival with IA treatment remained superior to
      that of FA and FAI but comparable to TA, and CR duration was only marginally
      shorter with FA. Landmark analysis showed the overall survival of responders to
      be superior to that of nonresponders, the difference remaining significant after
      adjustment for prognostic covariates. CONCLUSIONS: Although the newer regimens
      did not improve outcome, TA and CAT produced results comparable to those of IA
      and may be considered treatment alternatives. The TA regimen was particularly
      effective in RAEB patients and could be delivered safely, with low induction
      mortality. Our results indicated that although CR seemed associated with survival
      advantage, innovative post-remission managements represent a challenge because
      improvement in outcome is not likely to come from intensified therapy.

PMID- 11596014
TI  - Cyclosporin A for the treatment of cytopenia associated with chronic lymphocytic
      leukemia.
AB  - BACKGROUND: Autoimmune cytopenias are a frequent complication in patients with
      chronic lymphocytic leukemia (CLL). Anecdotal reports suggest that cyclosporin A
      (CsA) may be beneficial for patients with CLL-associated pure red cell aplasia.
      In the current study, the authors investigated the use of CsA in the management
      of anemia or thrombocytopenia of presumed autoimmune etiology associated with
      CLL. METHODS: Thirty-one patients with CLL and anemia or thrombocytopenia of
      presumed autoimmune etiology were treated with CsA at a dose of 300 mg/day.
      Sixteen patients (52%) had anemia (hemoglobin <or= 11 g/dL) and 29 patients (94%)
      had thrombocytopenia (platelet count <or= 100 x 10(9)/L). Seventeen patients
      (55%) had cytopenia that developed during the course of treatment with
      fludarabine-based regimens. Nineteen patients (61%) had received prior therapy
      for this complication using steroids, intravenous immunoglobulin, and/or
      splenectomy. RESULTS: Eighteen patients (62%) with thrombocytopenia and 10
      patients (63%) with anemia had a major response defined as an increase in the
      platelet count >or= 50 x 10(9)/L or an increase in hemoglobin >or= 3 g/dL. The
      median time to initial response was 3 weeks (range, 1-13 weeks) and the median
      time to best response was 10.5 weeks (range, 1-48 weeks). The median duration of
      response was 10 months (range, 1+-39+ months). Three patients with fludarabine
      associated cytopenias were able to receive further therapy with fludarabine with
      a lesser decrease in the platelet count. A modest decrease in the tumor burden
      was observed in six patients. The most common toxicity was <or= Grade 2
      (according to the National Cancer Institute's Common Toxicity Criteria) elevation
      of creatinine, which was observed in 6 patients (19%). Three patients developed
      opportunistic infections. CONCLUSIONS: CsA is an effective alternative for the
      treatment of anemia or thrombocytopenia of suspected autoimmune etiology,
      including those cases occurring in the course of treatment with fludarabine. A
      modest antileukemic effect was observed in some patients.

PMID- 11596015
TI  - Primary hepatic lymphoma: favorable outcome after combination chemotherapy.
AB  - BACKGROUND: Primary hepatic non-Hodgkin lymphoma (PHL) is a rare and difficult to
      diagnose lymphoproliferative disorder of unknown etiology. It is believed that
      the prognosis in affected patients is dismal, consisting of early recurrence and
      short survival. METHODS: A retrospective cohort review of patients with PHL
      diagnosed between 1974 and 1995 at a university cancer center was performed.
      RESULTS: Twenty-four patients with PHL were identified. Typically, the disease
      occurred in middle-aged men (median age, 50 years). The primary presenting
      complaint was right upper quadrant abdominal pain, with hepatomegaly found at
      physical examination. Serum liver enzymes, lactate dehydrogenase, and beta-2
      microglobulin levels all were elevated, but alpha-fetoprotein and
      carcinoembryonic antigen levels were within normal range. Hypercalcemia was found
      in 6 of 15 patients who were tested. Six of 10 patients who were tested were
      positive for the hepatitis C virus (HCV). Liver scans demonstrated either a
      solitary lesion or multiple lesions. Pathologic examination revealed diffuse
      large cell lymphoma in 23 patients (96%). Combination chemotherapy was the
      mainstay of treatment; surgery consisted of diagnostic biopsy. The complete
      remission rate was 83.3%, and the 5-year cause specific and failure free survival
      rates were 87.1% and 70.1%, respectively. HCV infection did not appear to
      influence the outcome of therapy. CONCLUSIONS: The outcome of patients with PHL
      who are treated with combination chemotherapy may be more favorable than that
      reported elsewhere. The frequent association of PHL with HCV infection observed
      in this series warrants further investigation.

PMID- 11596016
TI  - Reverse-transcriptase polymerase chain reaction of the maspin gene in the
      detection of bone marrow breast carcinoma cell contamination.
AB  - BACKGROUND: Maspin is a molecular marker used for the detection of contaminating
      breast carcinoma (BC) cells in peripheral blood and lymph nodes. However, its
      specificity has been questioned recently. The objective of this study was to
      verify the specificity of this marker and to determine the incidence of positive
      bone marrow results in patients with BC who are eligible for high-dose
      chemotherapy (HDT) both in early and advanced disease stages and before and after
      treatment. METHODS: Bone marrow specimens from 41 patients with BC as well as
      from 35 normal volunteers and 17 patients with hematologic tumors were examined
      for maspin transcript expression by a modified nested reverse transcriptase
      polymerase chain reaction technique. RESULTS: Maspin transcript was found in all
      normal and neoplastic breast tissues and in none of the 35 normal bone marrow
      specimens (specificity, 100%; 95% confidence interval, 90-100%). However, the
      transcript was found in 40% of the bone marrow samples from patients with
      hematologic malignancies. Thus, this marker appears very specific for
      discriminating between normal controls and patients with BC, but it cannot be
      considered disease specific. Among patients with BC, bone marrow was positive for
      the maspin transcript in 32% of patients with early-stage disease and in 75% of
      patients with metastatic disease before chemotherapy. After treatment, in 75% of
      patients with early-stage disease and in 50% of patients with metastatic disease,
      the bone marrow results became maspin negative. CONCLUSIONS: On the basis of the
      current data, although it is not disease specific, maspin is a reliable marker
      for detecting bone marrow molecular disease in patients with BC and should be
      considered for prospective studies as a prognostic indicator and as an assay for
      monitoring residual disease.

PMID- 11596017
TI  - Radiofrequency ablation in patients with primary breast carcinoma: a pilot study
      in 26 patients.
AB  - BACKGROUND: The authors performed a pilot trial of ultrasound-guided percutaneous
      radiofrequency ablation (RFA) in patients with T1 and T2 breast tumors 1) to
      confirm complete coagulative necrosis of tumor tissue and 2) to determine the
      safety and complications related to this treatment. METHODS: Twenty-six patients
      with biopsy-proven, invasive breast carcinoma underwent RFA of their breast
      tumors followed by immediate resection. Treatment was planned to ablate the tumor
      and a 5 mm margin of surrounding breast tissue. Tumor viability after RFA was
      assessed by hematoxylin and eosin and nicotinamide adenine dinucleotide vital
      staining. RESULTS: Twenty patients (77%) had T1 tumors, and six patients (23%)
      had T2 tumors. The mean greatest dimension of tumors that were treated with RFA
      was 1.8 cm (range, 0.7-3.0 cm). The mean treatment time for two-phase RFA
      treatment was 15 minutes and 23 seconds (range, from 6 minutes and 25 seconds to
      24 minutes and 54 seconds). Coagulation necrosis of the tumor was complete in 25
      of 26 patients (96%): One patient had a microscopic focus of viable tissue
      adjacent to the needle shaft site. A single patient (1 of 26 patients; 4%) had a
      complication related to RFA: a full thickness burn of the skin overlying a tumor
      that was immediately beneath the skin. CONCLUSIONS: This pilot experience with
      RFA in the treatment of patients with early-stage, primary breast carcinoma
      revealed that 1) coagulative necrosis of the entire tumor occurred in 96% of the
      patients, and 2) the treatment was safe, with only a 4% complication rate. The
      authors have initiated a trial of RFA alone (no resection) for patients with T1
      and T2 breast tumors that will include sentinel lymph node mapping and
      postablation irradiation.

PMID- 11596018
TI  - Anal gland carcinoma.
AB  - BACKGROUND: Anal gland carcinoma is a rare entity. The authors conducted a joint
      study of cases coded as definite or possible anal gland carcinoma from the
      archives of the Armed Forces Institute of Pathology and the Canadian Reference
      Center for Cancer Pathology. METHODS: Seven cases of potential anal gland
      carcinoma were identified from the Canadian files and 12 from the Armed Forces
      Institute of Pathology archives. Of these 19 cases, 14 had adequate material to
      allow clinical, histologic, and immunohistochemical analysis. RESULTS: Seven of
      these 14 cases met a modified World Health Organization (WHO) definition of anal
      gland carcinoma. The mean age of these patients was 66 years (range, 60-72
      years), with a male-to-female ratio of 6:1. The tumors were composed of
      haphazardly dispersed, small glands with scant mucin production that invaded the
      wall of the anorectal area with no obvious intraluminal component observed
      clinically or microscopically. Immunohistochemical studies were performed on all
      seven of these cases, revealing cytokeratin (CK) 7+/CK 20- expression in six
      cases, and CK 7+/CK 20+ expression in one case. The remaining seven cases showed
      no intraluminal component but did not meet a modified WHO definition of anal
      gland carcinoma. This group included three mucinous adenocarcinomas (two
      clinically arising in anal fistulas), all of which were CK 7+/CK 20+, and a
      rectal-type adenocarcinoma that was CK 7-/CK 20+. There was also a tumor
      interpreted as probable rectal-type adenocarcinoma that was CK 7+/CK 20+, and a
      tumor interpreted as probable squamous cell carcinoma that was CK 7-/CK 20-. The
      seventh tumor in this group, which could not be classified, was CK 7+/CK 20-.
      CONCLUSIONS: A useful and discriminating definition of anal gland carcinoma is an
      anal canal tumor composed of haphazardly dispersed, small glands with scant mucin
      production invading the wall of the anorectal area without an intraluminal
      component. The glands are positive for CK 7.

PMID- 11596019
TI  - Preoperative serum interleukin-18 level as a postoperative prognostic marker in
      patients with gastric carcinoma.
AB  - BACKGROUND: Interleukin-18 (IL-18), a recently described cytokine produced mainly
      by macrophages, stimulates interferon-gamma (IFN-gamma) production by natural
      killer cells and T cells. Although it has been reported that serum IL-18 levels
      are higher in patients with advanced tuberculosis and acute graft-versus-host
      disease compared with normal controls, the authors found no reports regarding
      serum IL-18 levels in patients with malignant solid tumors. The purpose of this
      study was to determine serum IL-18 levels and their clinical significance in
      patients with gastric carcinoma. METHODS: Peripheral blood samples were obtained
      from 94 patients with gastric carcinoma who underwent curative surgery and from
      50 healthy volunteers. The serum IL-18 level, the IFN-gamma, level, and the
      Helicobacter pylori (HP) serology status were determined in each sample with an
      enzyme-linked immunosorbent assay. RESULTS: The mean serum IL-18 level for all
      patients was significantly higher compared with the mean level in healthy
      volunteers (P < 0.01). IFN-gamma titers were below the level of detection in all
      samples tested. When the patients were subdivided into groups, it was found that
      the serum IL-18 level in patients with Stage II and III disease was significantly
      higher compared with the level found in healthy volunteers (P < 0.01). The serum
      IL-18 level decreased after patients underwent surgical resection. However, there
      was no significant difference in the serum IL-18 level between healthy controls
      and patients with Stage I or IV disease. Patients with IL-18 levels >or= 310
      pg/mL (i.e., equal to or greater than the mean levels +/- 1 standard deviation in
      the healthy volunteers) experienced a significantly lower survival rate compared
      with patients who had IL-18 levels < 310 pg/mL after undergoing surgery (P <
      0.05) despite a lack of any discernible difference in clinicopathologic factors
      between the two groups. The serum IL-18 level was identified as an independent
      postoperative prognostic factor in multivariate survival analysis using a Cox
      proportional hazards model (hazard ratio, 4.89; P = 0.01). There was no
      significant correlation between HP serology status and serum IL-18 levels.
      CONCLUSIONS: The preoperative serum IL-18 level may represent a significant
      postoperative prognostic determinant in patients with gastric carcinoma. Its
      function in the host immune system remains to be elucidated.

PMID- 11596020
TI  - Genetic detection of lymph node micrometastases in patients with gastric
      carcinoma by multiple-marker reverse transcriptase-polymerase chain reaction
      assay.
AB  - BACKGROUND: Some patients with gastric carcinoma experience local disease
      recurrence despite undergoing curative resection of the tumor and regional lymph
      nodes (LNs), suggesting the presence of occult micrometastases. To evaluate the
      presence of gastric carcinoma micrometastasis in patients with otherwise
      histologically negative LNs, the authors established and tested a multiple-marker
      reverse transcriptase-polymerase chain reaction (RT-PCR) assay. METHODS: The
      authors assessed 435 LNs from 28 patients with gastric carcinoma who underwent
      gastrectomy with lymphadenectomy using the multiple-marker RT-PCR assay in
      addition to histologic examination. Carcinoembryonic antigen (CEA), cytokeratin
      20 (CK-20), and MAGE-3 gene markers were used in this assay. LNs were scored
      positive for metastasis if at least one marker was positive. The presence of LN
      micrometastases also was verified by immunohistochemistry in histologically
      negative and RT-PCR positive LNs. RESULTS: Sixty-nine of 435 LNs (16%) were
      positive for CEA (12%), CK-20 (10%), or MAGE-3 (5%). None of 16 control LNs
      obtained from disease free patients was positive by RT-PCR assay. Of 414
      histologically negative LNs, 50 LNs (12%) were scored as positive for metastasis
      by the assay. Of 26 patients who underwent curative resection, the disease stage
      was upgraded in 10 patients by genetic diagnosis (from Stage IA to Stage IB in 5
      patients, from Stage IB to Stage IIIA in 2 patients, from Stage IB to Stage IV in
      1 patient, from Stage IB to Stage II in 1 patient, and from Stage II to Stage
      IIIB in 1 patient). In the latter 10 patients, immunohistochemistry identified LN
      micrometastases in 4 patients. Two patients with micrometastasis by genetic
      diagnosis had recurrent disease within 1 year. CONCLUSIONS: The current results
      indicate that the multiple-marker RT-PCR assay is a useful tool for the detection
      of micrometastases in regional LNs in patients with gastric carcinoma and may
      improve the staging system of gastric carcinoma for these patients.

PMID- 11596021
TI  - Mitoxantrone in patients with prostate specific antigen progression after local
      therapy for prostate carcinoma.
AB  - BACKGROUND: Molecular mechanisms of chemotherapy resistance are present in
      prostate carcinoma, some of which increase after androgen ablation (AA) therapy.
      Therefore, the authors hypothesized that chemotherapy in patients with prostate
      specific antigen (PSA) progression after local therapy, before androgen ablation
      therapy, will have greater antitumor activity. METHODS: Twenty-three hormone
      naive patients with PSA progression after prostatectomy or radiation therapy were
      registered in this study. Twenty-two were treated with 10 mg/m(2) of mitoxantrone
      initially, followed by 12 mg/m(2) every 3 weeks for a maximum of 8 cycles.
      Prostatectomy specimens were assessed, when possible, for topoisomerase II alpha,
      multidrug resistance protein MRP, and bcl-2 by immunohistochemistry. RESULTS:
      Twenty-two patients received a total of 131 cycles of therapy. Three patients had
      transient Grade 3 or 4 neutropenia without fever. During treatment, 10 of 22
      patients showed a decrease in PSA, without an associated decrease in
      testosterone. In this group of 10 patients, the mean PSA decrease was 29% at 3
      months and 43% at 6 months. Overall, 4 of 22 patients had a decrease in PSA of
      greater than or equal to 50%. The PSA decreased in three of seven patients whose
      cancer overexpressed MRP and in three of seven patients who overexpressed bcl-2.
      No patient with overexpression of topoisomerase II alpha (n = 4) had a decrease
      in PSA during the study. CONCLUSIONS: To the authors' knowledge, this is the
      first reported study of mitoxantrone in patients with hormone-naive prostate
      carcinoma and PSA progression after local therapy; mitoxantrone was safe and
      biochemically active, similar to prior studies in hormone refractory prostate
      carcinoma, suggesting that critical molecular mechanisms of chemotherapy
      resistance are present independent of AA. Further studies are warranted to
      determine whether pharmacogenomic assessment of topoisomerase II, MRP, or bcl-2
      may predict for response to mitoxantrone.

PMID- 11596022
TI  - Significance of serum amyloid A on the prognosis in patients with renal cell
      carcinoma.
AB  - BACKGROUND: Evidence of systemic inflammation, i.e., elevation of serum C
      reactive protein, interleukin-6, and/or the erythrocyte sedimentation rate, is
      correlated to poorer prognosis of patients with renal cell carcinoma (RCC). Serum
      amyloid A (SAA) has been recognized mainly as acute-phase reactant. METHODS:
      Serum SAA from 72 patients with RCC were examined. Thirty-eight of 72 patients
      with RCC had elevated SAA compared with 17 healthy donors. RESULTS: The disease
      specific survival rate was significantly lower in the elevated SAA group, and SAA
      level was shown to be an independent prognostic factor by univariate and
      multivariate analysis. CONCLUSIONS: Evaluation of serum SM level in RCC patients
      may be a useful prognostic indicator.

PMID- 11596023
TI  - CpG hypermethylation of the promoter region inactivates the estrogen receptor
      beta gene in patients with prostate carcinoma.
AB  - BACKGROUND: The down-regulation of the estrogen receptor-beta (ERbeta) gene is
      associated with several malignancies, including prostate carcinoma. The purpose
      of the current study was to investigate the mechanisms of ERbeta inactivation
      through the analysis of CpG methylation of the promoter region of ERbeta gene.
      METHODS: ERbeta protein expression was examined by immunohistochemistry in 23
      cases of human prostate carcinoma and 40 cases of benign prostatic hyperplasia
      (BPH). DNA was extracted from these tissues and processed for sodium bisulfite
      genomic sequencing. The percentage of methylation of CpG sites in the promoter
      region of ERbeta (-376 to -117), which contains 19 CpG sites, was determined from
      genomic sequencing data. The prostate carcinoma cell lines DU145 and ND1 were
      treated with the demethylating agent 5-AZAC and ERbeta mRNA expression was
      analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: In BPH
      tissues, ERbeta protein expression was found mainly in epithelial cells. ERbeta
      protein expression was lacking in 83% of prostate carcinoma samples (19 of 23
      samples) whereas all cases of BPH (40 of 40) demonstrated expression of ERbeta
      protein. The mechanism of inactivation of the ERbeta gene in prostate carcinoma
      was CpG methylation because the degree of methylation at all CpG sites within the
      promoter region between -376 and -117 was higher in prostate carcinoma samples
      compared with BPH tissues. Nine of 19 CpG sites within the promoter region of
      ERbeta displayed significant differences in methylation between prostate
      carcinoma and BPH samples. The prostate carcinoma cell lines appeared to lack
      ERbeta expression. However, 5-AZAC treatment restored ERbeta expression in those
      cell lines, suggesting that methylation inactivates the ERbeta gene in prostate
      carcinoma. CONCLUSIONS: The results of the current study demonstrate, for what we
      believe to be the first time, that the inactivation of the ERbeta gene in
      prostate carcinoma occurs through CpG methylation of the promoter region of this
      gene.

PMID- 11596024
TI  - Long-term results of treatment for prostate carcinoma by staging pelvic lymph
      node dissection and definitive irradiation using low-dose rate temporary iridium
      192 interstitial implant and external beam radiotherapy.
AB  - BACKGROUND: The objective of this study was to evaluate long-term treatment
      outcome of definitive irradiation by using temporary interstitial implant and
      limited dose of external beam radiotherapy in treatment of localized prostate
      carcinoma. METHODS: In total, 536 patients with biopsy-proven adenocarcinoma of
      the prostate, classification T1-T3, underwent staging pelvic lymph node
      dissection and brachytherapy delivering an average tumor dose of 30 grays (Gy),
      supplemented by external beam radiation therapy for an additional dose of 36 Gy
      delivered over 4 weeks. One hundred of 536 (18%) patients had pathologic D1
      disease. A total of 181 patients had undergone transurethral prostatectomy before
      the treatment. Repeat prostate biopsy was performed on 132 patients 18 or more
      months after treatment. None of the patients received neoadjuvant or adjuvant
      hormone therapy. RESULTS: Cumulative disease free survival (DFS) including
      biochemical DFS at 10 and 15 years for classification T1B,C was 78% and 72%; for
      T2A, 78% and 78%; for T2B,C, 68% and 66%; and for T3A-C, 45% and 45%,
      respectively. Cause specific survival for the entire group at 10 and 15 years was
      89% and 87%, respectively. Severe complications occurred only in the early
      developmental phase of the study. CONCLUSIONS: In univariate analysis, the
      clinical stage, histologic grade, pretreatment PSA level, lymph node status, and
      results of repeat posttreatment biopsy were all independently significant
      prognostic factors. However, the authors' study indicates that in multivariate
      analysis, only two factors emerged with statistical significance-the status of
      pelvic lymph nodes and the results of posttreatment biopsy. This signifies the
      importance of local tumor control to achieve ultimate cure and the importance of
      assessment of pelvic lymph nodes before definitive local therapy other than
      radical prostatectomy, especially in the high-risk group.

PMID- 11596025
TI  - Use of the aromatase inhibitor anastrozole in the treatment of patients with
      advanced prostate carcinoma.
AB  - BACKGROUND: Men with prostate carcinoma initially respond to therapies designed
      to inhibit androgen secretion or block its action. Later, the tumors in these
      patients become refractory to androgen-related therapies. Therefore, additional
      hormonal maneuvers that would benefit these men currently are needed. Reports of
      androgen receptor mutations and historic clinical observations raised the
      hypothesis that estrogens might be involved in the proliferation of androgen
      refractory prostate carcinoma. METHODS: To explore this hypothesis, 14 men with
      advanced prostate carcinoma that was refractory to medical or surgical
      orchiectomy and antiandrogens were entered into a clinical Phase II trial
      involving suppression of estrogens. After complete evaluation, each patient
      received 1 mg daily of the third-generation aromatase inhibitor anastrozole until
      disease progression. Follow-up included serial determinations of prostate
      specific antigen (PSA), measurements of evaluable lesions, and assessment of
      intensity of pain. RESULTS: No patient experienced an objective response or
      disease stabilization as measured by PSA level or the greatest dimension of the
      lesion. Minimal improvement of bone pain was reported in two patients receiving
      intensive analgesic medication. CONCLUSIONS: It was concluded that the dependence
      of androgen-insensitive prostate carcinoma on estrogens for proliferation is
      uncommon and that aromatase inhibitors may not have a place in the treatment of
      prostate carcinoma at this stage of the disease.

PMID- 11596026
TI  - Family cancer history and susceptibility to oral carcinoma in Puerto Rico.
AB  - BACKGROUND: Use of alcohol and tobacco are the major risk factors for cancers of
      the oral cavity and pharynx in most of the world. A heritable component to oral
      carcinoma risk also has been suggested, although only limited data are available
      on familial aggregation of this disease. METHODS: A population-based case-control
      study of 342 subjects with carcinomas of the oral cavity and pharynx (oral
      carcinoma) and 521 controls was conducted in Puerto Rico. The relation between
      family history of carcinomas of the oral cavity, the upper aerodigestive tract
      (UADT), and other selected sites with risk of oral carcinoma was explored using
      logistic regression modeling techniques. RESULTS: Risk of oral carcinoma was
      elevated for subjects reporting a first-degree relative with carcinoma of the
      oral cavity (odds ratio [OR], 2.5; 95% confidence interval [CI], 0.8-8.0) or any
      UADT carcinoma (OR, 2.6; 95% CI, 1.4-4.8). The increased risk associated with
      family history of UADT carcinoma tended to be greatest for subjects with known
      risk factors (i.e., heavy consumption of alcohol and/or tobacco and infrequent
      intake of raw fruits and vegetables) and with oral carcinoma diagnoses at ages
      younger than 65 years. CONCLUSIONS: These findings are consistent with a
      heritable component to oral carcinoma, although shared lifestyle risk factors may
      be partially involved.

PMID- 11596027
TI  - Comorbidity and survival of elderly head and neck carcinoma patients.
AB  - BACKGROUND: Alcohol and tobacco, the primary etiologic agents for head and neck
      carcinoma (HNCA), cause other chronic diseases and may contribute to the high
      prevalence of comorbid conditions and generally poor survival of persons with
      HNCA. METHODS: The authors explored the prognostic role of comorbidity in persons
      with HNCA using Health Care Finance Administration Medicare (HCFA) files linked
      with the appropriate files of the Surveillance, Epidemiology, and End Results
      (SEER) Program. The Charlson comorbidity index was applied to in-patient data
      from the HCFA files. The SEER data were used to ascertain survival and identify
      persons with HNCA diagnosed from 1985 to 1993 (n = 9386). RESULTS: In a
      proportional hazards regression model adjusted for age and historic stage at
      diagnosis, race, gender, marital status, socioeconomic status, histologic grade,
      anatomic site, treatment, and pre-1991 diagnosis, Charlson index scores of 0, 1,
      and 2+ had estimated relative hazards (RHs) with 95 confidence intervals (CIs) of
      1.00, 1.33 (95% CI, 1.21-1.47), and 1.83 (95% CI, 1.64-2.05), respectively (P
      value for trend < 0.0001). The adjusted RH for a Charlson index score of 1 or
      more compared with 0, using stratified models, was found to be greater in whites
      (RH, 1.55; 95% CI, 1.43-1.67) than blacks (RH, 1.24; 95% CI, 0.96-1.60), local
      (RH, 1.72; 95% CI, 1.50-1.96) versus distant stage (RH, 1.25; 95% CI, 1.00-1.56),
      and age 65-74 years (RH, 1.53; 95% CI, 1.38-1.69) versus age 85+ years (RH, 1.42;
      95% CI, 1.09-1.84). CONCLUSIONS: This study establishes comorbidity as a
      predictor of survival in an elderly HNCA population and lends support to the
      inclusion of comorbidity assessment in prognostic staging of patients with HNCA
      diagnosed after 65 years of age.

PMID- 11596028
TI  - pRb2/p130 protein expression is correlated with clinicopathologic findings in
      patients with oral squamous cell carcinoma.
AB  - BACKGROUND: pRb2/p130 is one of the retinoblastoma (Rb) gene family and a
      suppressor oncogene. Immunohistochemically, the expression of pRb2/p130 was
      reported to be correlated inversely with the degree of malignancy in lung
      carcinoma and endometrial carcinoma. In the current study, the correlation
      between expression of pRb2/p130 and clinicopathologic factors in oral squamous
      cell carcinoma was investigated. METHODS: One hundred twenty-two specimens from
      patients with oral squamous cell carcinoma were investigated by staining with a
      polyclonal antibody against pRb2/p130. The correlation between the expression of
      pRb2/p130 and various clinicopathologic factors was studied. RESULTS: Positive
      staining for pRb2/p130 was observed in 61 of 122 cases (50.0%). pRb2/p130
      expression was found to be correlated significantly with clinical stage (P =
      0.050), cervical lymph node metastasis (P = 0.035), and tumor differentiation (P
      = 0.050). In the entire group a significantly reduced 5-year cumulative survival
      rate was observed in patients with pRb2/p130-negative tumors compared with
      patients whose tumors positively expressed pRb2/p130 (P = 0.0004). When tested
      with Cox proportional hazards regression analysis, the most significant
      independent prognostic factor for the entire group of 122 patients was found to
      be pRb2/p130 expression. CONCLUSIONS: Expression of pRb2/p130 may be a good
      prognostic indicator in patients with oral squamous cell carcinoma and also may
      be utilized for the subclassification of tumors with the Grade 3 mode of
      carcinoma invasion.

PMID- 11596029
TI  - Chinese nasopharyngeal carcinoma patients treated with radiotherapy: association
      between satisfaction with information provided and quality of life.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is highly prevalent in southern China.
      Prominent acute side effects of radiotherapy create problems in daily living and
      working that can generate considerable financial difficulties. A better
      adjustment to a diagnosis of NPC appears to be associated with an improved rate
      of recovery, a better quality of life (QoL), a quicker return to work, and normal
      functioning. Patient satisfaction with physician consultation and the way
      information is provided in particular may have significant bearing on QoL. The
      current study reports on short-term QoL after radiotherapy in NPC patients as a
      function of satisfaction with the information provided. METHODS: Newly referred
      Hong Kong Chinese NPC patients (n = 211) completed interview measures at baseline
      before the initiation of radiotherapy, at 4 months after baseline (immediate
      posttreatment consultation) (FU 1), and again at 8 months (short-term
      postradiation period) after baseline (FU 2). Satisfaction with the information
      provided was measured by five items selected from the cognitive subscale of the
      Medical Interview Satisfaction Scale (MISS). QoL was measured by the Chinese
      version of the Functional Assessment of Cancer Therapy-General Scale (FACT-G
      (Ch)). RESULTS: After adjustment for overall patient satisfaction (the PSQ-9),
      optimism, worry about family, anger, eating ability, subjective health, family
      income, and occupation at FU 1, treatment between baseline and FU 1, and disease
      recurrence after baseline, the 5-item MISS at FU 1 (beta = 0.21, P < 0.01) was
      found to significantly predict patient QoL at FU 2. Adjustment for baseline QoL
      and disease stage did not appear to alter this relation (beta = 0.20, P < 0.01).
      CONCLUSIONS: To the authors' knowledge, there is very little research concerning
      NPC. The results of the current study reinforced the need to improve physicians'
      information provision during consultations with Chinese NPC patients shortly
      after the end of treatment.

PMID- 11596030
TI  - Expression of Fas antigen (CD95) in peripheral blood lymphocytes and in liver
      infiltrating, cytotoxic lymphocytes in patients with hepatocellular carcinoma.
AB  - BACKGROUND: Fas-expressing cytotoxic T lymphocytes (CTLs) are important antitumor
      immune effector cells in patients with hepatocellular carcinoma (HCC). The role
      of transforming growth factor beta 1 (TGF-beta1) in modulating the expression of
      Fas by CTLs is not known in HCC. The objectives of this study were to
      characterize the expression of Fas by CTLs and natural killer (NK) cells among
      peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) in
      patients with HCC and to correlate the association, if any, with serum TGF-beta1
      levels. METHODS: PBLs from 18 patients with HCC and TILs from 5 HCC liver
      specimens were isolated, and Fas expression was analyzed by three-color flow
      cytometry. The results were compared with results from normal control volunteers
      (n = 19 individuals). Serum TGF-beta1 levels in patients with HCC were measured
      by enzyme-linked immunosorbent assay. RESULTS: The median percentage of Fas
      expression by CD3 positive T cells was significantly higher in patients with HCC
      compared with normal controls (54.37% vs. 32.03%, respectively; P = 0.0036), and
      this was attributable solely to Fas expression by CD4 positive PBLs (54.46% vs.
      34.90%, respectively; P = 0.0234). In contrast, Fas expression was significantly
      higher in all the subtypes of TILs (CD3 positive, CD4 positive, CD8 positive, NK
      cells, and natural T cells) compared with controls (all P values were < 0.001).
      Tumor size was inversely proportional to the TGF-beta1 levels (correlation
      coefficient [r] = -0.725; P < 0.0001), which were correlated inversely with Fas
      expression by CD4 positive PBLs (r = -0.516; P = 0.01). CONCLUSIONS: In patients
      with HCC, TILs exhibit significantly increased expression of Fas compared with
      PBLs that may enhance their susceptibility to apoptotic mechanisms. Larger tumors
      were associated with lower serum TGFbeta1 levels, and this was correlated with
      greater Fas expression by CD4 positive PBLs.

PMID- 11596031
TI  - Paclitaxel and carboplatin adjuvant therapy alone or with radiotherapy for
      resected nonsmall cell lung carcinoma: a feasibility study of the Minnie Pearl
      Cancer Research Network.
AB  - BACKGROUND: The objective of this study was to determine the feasibility and
      toxicity of paclitaxel and carboplatin given in the adjuvant setting alone for
      patients with resected Stage IB disease and combined with radiotherapy for
      patients with resected Stages II and IIIA disease and selected patients with
      Stage IIIB and IV disease (Revised International System for Staging of Lung
      Cancer). METHODS: One hundred two patients with resected nonsmall cell lung
      carcinoma were treated in the postoperative period with 3 courses of paclitaxel
      200 mg/m(2) intravenously (i.v.) over 1 hour and carboplatin area under the curve
      of 6 i.v. every 3 weeks for 3 courses. Patients with Stage IB received no further
      therapy, and those with higher stages also subsequently received radiotherapy
      plus concurrent weekly paclitaxel and carboplatin over 6 weeks. The median age
      was 61 years, with 56 men and 46 women, and the predominant histologic type was
      adenocarcinoma. Twenty pneumonectomies, 80 lobectomies, and 2 other procedures
      were performed. Ninety percent of the patients (92 of 102) received all 3 courses
      of adjuvant paclitaxel and carboplatin (84% received full doses). Seventy-three
      percent received full doses of radiotherapy and concurrent weekly chemotherapy
      (49 of 67 patients), and 14 others received greater than 75% of the radiotherapy
      and concurrent chemotherapy. RESULTS: Toxicity of the chemotherapy was mild with
      only three hospitalizations for neutropenia and fever and no treatment-related
      deaths. Severe hypersensitivity occurred in six patients (6%). Concurrent
      radiation therapy and weekly chemotherapy also was well tolerated with the
      exception of Grade 3-4 esophagitis observed in 27% (17 of 67 patients). Follow-up
      was short with a median of 10 months, and 65% of all patients remained
      progression free. CONCLUSIONS: Three courses of paclitaxel and carboplatin is
      tolerable, feasible, and can be delivered in most patients in the adjuvant
      setting. Subsequently, in higher stage patients, concurrent postoperative
      radiation therapy and weekly paclitaxel and carboplatin is well tolerated and
      delivered in most patients. Definitive prospective randomized Phase III adjuvant
      trials are warranted.

PMID- 11596032
TI  - Analysis of MUC4 mucin expression in lung carcinoma cells and its immunogenicity.
AB  - BACKGROUND: MUC4 has been cloned from tracheobronchial mucosa cDNA and reportedly
      is highly expressed in some human malignancies, including lung carcinoma.
      However, little is known about molecular and biologic characteristics. The
      authors analyzed expression levels of MUC4 mRNA and protein in lung carcinoma
      cells and analyzed the immunogenicity of this mucin. METHODS: Nine cultured lung
      carcinoma cell lines and 29 tumor samples from patients with lung carcinoma were
      examined by Northern hybridization for MUC4 mRNA expression and by flow cytometry
      or an immunohistochemical staining for its protein expression. Sera from the
      patients were examined for their reactivity with MUC4 by enzyme-linked
      immunosorbent assay. RESULTS: Forty-four percent of the cell lines and 72% of the
      tumor samples showed high levels of MUC4 mRNA expression. Although MUC4 protein
      was not detected in any live carcinoma cell lines by flow cytometry using rabbit
      antisera reactive with the MUC4 core, pretreatment with paraformaldehyde and
      sialidase resulted in successful detection of the protein in 50% of the cell
      lines. An immunohistochemical study revealed that 67% of the tumors exhibited
      MUC4 protein expression without any digestion. In 29% of the patients, high
      levels of anti-MUC4 immunoglobulin M or immunoglobulin G were detected.
      CONCLUSIONS: MUC4 protein expression was elevated in lung carcinoma tissues
      because of the increase in its mRNA expression and deglycosylation on its core.
      This mucin is sufficiently immunogenic to elicit humoral and cellular immunity
      specific for MUC4 in patients with malignant disease. MUC4 is expected to be
      useful as a target antigen in immunotherapy for patients with carcinoma of the
      lung.

PMID- 11596033
TI  - Phase II trial of weekly docetaxel in second-line therapy for nonsmall cell lung
      carcinoma.
AB  - BACKGROUND: The authors conducted a Phase II study to evaluate the activity and
      toxicity of weekly docetaxel in second-line therapy for nonsmall cell lung
      carcinoma (NSCLC). METHODS: Patients with documented recurrent or refractory
      NSCLC, previously treated with no more than one chemotherapy regimen, were
      eligible if they had a performance status (PS) of 0-2, measurable or evaluable
      disease, and adequate organ function. Patients were treated with docetaxel 36
      mg/m(2)/week for 6 consecutive weeks, administered intravenously with
      dexamethasone premedication. Cycles were repeated every 8 weeks. RESULTS: Thirty
      one patients were enrolled. One patient was ineligible because of uncontrolled
      brain metastases. Hematologic toxicity was minimal. Nonhematologic toxicities
      were modest except for diarrhea and cumulative fatigue. There were no treatment
      related deaths. The overall response rate was 10% (95% confidence interval [CI],
      1.6-29%). The median survival time (MST) was 8.0 months. and the 1-year survival
      rate was 31% (95% CI, 17- 58%). Patients with PS 0-1 had a MST of 11.9 months
      with 1-year survival of 42%. CONCLUSIONS: Weekly docetaxel is very well tolerated
      as second-line therapy for NSCLC. The activity of this regimen appears to be
      comparable to the standard 3-week schedule. This regimen offers new opportunities
      for combination regimens, both as first- and second-line therapy for NSCLC.

PMID- 11596034
TI  - Expression of eukaryotic translation initiation factors 4E and 2alpha is
      increased frequently in bronchioloalveolar but not in squamous cell carcinomas of
      the lung.
AB  - BACKGROUND: When resting cells are stimulated by growth factors, an increase in
      protein synthesis follows that depends in part on two key eukaryotic translation
      initiation factors, 4E and 2alpha (eIF-4E and eIF-2alpha, respectively). In the
      normal cell, expression and activity of both factors are increased transiently,
      whereas they become elevated constitutively in oncogene-transformed cultured
      cells, and overexpression of either initiation factor in rodent cells makes them
      tumorigenic. In this study, the authors investigated an association between the
      expression of these translation initiation factors and lung carcinogenesis.
      METHODS: The authors analyzed the expression of the protein synthesis initiation
      factors eIF-4E and eIF-2alpha by immunohistochemistry in bronchioloalveolar (BA)
      and squamous cell (SC) carcinomas of the lung. Western blot analysis was
      performed to validate the specificity of antibodies in detecting their cognate
      proteins. RESULTS: Both eIF-4E and eIF-2alpha were increased frequently in BA
      carcinomas, whereas only rarely did SC carcinomas demonstrate elevation of these
      translation initiation factors. An analysis of cyclin D1 expression did not show
      a strict correlation with the expression of eIF-4E and eIF-2alpha. CONCLUSIONS:
      Increased expression of either one or both translation initiation factors may
      facilitate accelerated growth and division of neoplastic cells in BA carcinoma of
      the lung. However, the current findings suggest a possibility that increased cell
      growth and proliferation in SC carcinoma may be achieved through a mechanism
      independent of increases in eIF-4E and eIF-2alpha expression.

PMID- 11596035
TI  - A lipophilic vasoactive intestinal peptide analog enhances the antiproliferative
      effect of chemotherapeutic agents on cancer cell lines.
AB  - BACKGROUND: Vasoactive intestinal peptide (VIP) is one of several small
      neuropeptides that affect cancer growth. A lipophilic VIP analog, stearyl-Nle(17)
      neuroten-sin(6-11)VIP(7-28) (SNH) that inhibited lung carcinoma growth has been
      described previously. The experiments performed were clonogenic assays in vitro
      and tumor xenografts in nude mice in vivo. These studies were now extended to
      colon carcinoma and to combination therapy with chemotherapeutic agents. METHODS:
      Assays were performed with cell lines, and tumor proliferation was assessed using
      the (3-[4,5-dimethylthiazol-2-yl-5]-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H
      tetrazolium) (MTS) colorimetric assay for mitochondrial function of living cells.
      RESULTS: The lipophilic analog (SNH) enhanced the antiproliferative activity of
      diverse chemotherapeutic agents: doxorubicine (antibiotic); vinorelbine (vinca
      alkaloid, antimicrotubule formation); paclitaxel (antimicrotubule agent);
      gemcitabine (antimetabolite); irinotecan (topoisomerase I inhibitor); and
      cisplatin (platinum compound acting as an alkylating agent). In all cases, the
      antiproliferative effect of SNH and the chemotheraputic agent was at least
      additive and for some combinations and concentrations even synergistic. For
      example, 2 microM of the antagonist that produced a 15-20% growth inhibition in
      the nonsmall cell lung carcinoma cell line reduced the IC(50) by 2-4-fold for
      most of the chemotherapeutic agents tested. Higher analog concentrations were
      even more efficacious. Similar results were obtained with colon carcinoma cell
      lines. CONCLUSIONS: Chemotherapeutic treatment of advanced solid tumors, such as
      nonsmall cell lung carcinoma, colon carcinoma, or prostate carcinoma, achieves a
      response rate of between 10% and 30% with significant toxicity. Combination
      therapy with the lipophilic VIP analog SNH and the preferred chemotherapeutic
      agent may greatly enhance the response rate, and by permitting a dose reduction,
      should significantly reduce side effects.

PMID- 11596036
TI  - Comparison of p53 mutations in patients with localized osteosarcoma and
      metastatic osteosarcoma.
AB  - BACKGROUND: In some malignancies, p53 mutations are associated with tumor
      progression. To address the role of p53 mutations in the development and
      progression of osteosarcoma, the authors analyzed specimens from 247 patients
      with primary localized osteosarcomas and 25 patients with osteosarcomas that were
      metastatic at the time of diagnosis. The group included 27 matched biopsy
      resection specimens and 21 biopsy-metastasis paired specimens. METHODS: The
      authors examined the nature and location of p53 mutations (exons 4-10) by
      polymerase chain reaction-single-strand conformation polymorphism and confirmed
      mutations by direct DNA sequencing. RESULTS: The overall frequency of p53
      mutations was 22% (60 of 272 specimens), with 13 of 60 mutations located in exons
      4 or 10. A similar proportion of localized osteosarcomas had alterations of the
      p53 gene (55 of 247 specimens; 22.3%) compared with tumors from patients who had
      metastases at the time of diagnosis (5 of 25 specimens; 20%; P = 0.96). Patients
      who had p53 missense mutations were older compared with patients who had nonsense
      alterations or a wild type gene (P = 0.01). Examination of paired biopsy
      resection and biopsy-metastasis specimens revealed that the p53 status was
      concordant between the biopsy and later tumor specimens in all patients.
      CONCLUSIONS: The p53 mutation status did not differentiate between patients who
      presented with a localized osteosarcoma and those who presented with metastases
      at the time of diagnosis. The current data indicate that p53 mutations are not
      late events in osteosarcoma tumor progression, because they are evident before
      the development of metastases. The inclusion of exons 4 and 10 increased the
      sensitivity of the analysis.

PMID- 11596037
TI  - Penetration of dacarbazine and its active metabolite 5-aminoimidazole-4
      carboxamide into cutaneous metastases of human malignant melanoma.
AB  - BACKGROUND: Dacarbazine has been on the market for approximately 3 decades but
      remains the most effective single agent available for the therapy of metastatic
      malignant melanoma (MMM). Most MMMs, however, respond poorly to dacarbazine
      therapy. Apart from tumor resistance at a molecular level, several studies
      support the notion that therapeutic failure in tumor therapy also might be
      attributed to an impaired transcapillary drug transfer. METHODS: On the basis of
      this hypothesis, the authors measured intratumor transcapillary transfer rates of
      dacarbazine and its active metabolite 5-aminoimidazole-4-carboxamide (AIC) by in
      vivo microdialysis after intravenous administration of dacarbazine at doses of
      200 mg/m(2) to 1000 mg/m(2) (n = 7) in patients suffering from MMM. RESULTS: For
      all doses, area under the concentration curve (AUC) values for dacarbazine and
      AIC were not significantly different between plasma and tumor interstitium with
      AUC(tumor)/AUC(plasma) ratios of 0.97 +/- 0.08 (mean +/- standard error of the
      mean) for dacarbazine and 0.76 +/- 0.22 for AIC. AUC(0-240) values for
      dacarbazine and AIC measured in plasma correlated closely with corresponding
      AUC(0-240)values measured in the interstitium of MMMs with values of r(s) = 0.82
      (P = 0.042) and r(s) = 0.90 (P = 0.037), respectively. CONCLUSIONS: The results
      of this study indicate favorable tumor penetration characteristics of dacarbazine
      and its active metabolite AIC. The relative lack of response to antineoplastic
      therapy with dacarbazine, thus might be explained by resistance of melanoma cells
      at a molecular level rather than by an inability of dacarbazine and AIC to
      penetrate into the interstitium of MMM.

PMID- 11596038
TI  - Hyperthermic pleural perfusion with cisplatin: early clinical experience.
AB  - BACKGROUND: The preferred treatment for patients with pleural tumors or tumors
      with pleural extension has not been determined. Systemic and local modalities
      were studied, including intrapleural chemotherapy and hyperthermia, which mainly
      have been investigated separately. The objective of this study was to investigate
      the feasibility, toxicity and early results of a multimodality treatment
      consisting of surgery, chemotherapy, and hyperthermia in one session for the
      treatment of patients with pleural malignancies. METHODS: From November 1994 to
      September 1998, 26 patients (7 patients with mesothelioma, 11 patients with
      thymic neoplasms, and 8 patients with other tumors) underwent intraoperative
      hyperthermic pleural perfusion (HPP). Perfusion was performed with a roller pump
      and a heat exchanger. Cisplatin was added when the temperature stabilized to a
      mean of 40.8 degrees C (range, 40.2-41.5 degrees C). Dosages of cisplatin used
      were 60 mg in 2 patients, 100 mg in 2 patients, 120 mg in 1 patient, 150 mg in 18
      patients, and 200 mg in 3 patients. The patients underwent the following
      associated surgeries: extended extrapleural pneumonectomy in 8 patients,
      resection of tumor without pleurectomy in 4 patients, resection of tumors with
      pleurectomy in 10 patients, and exploration and HPP only in 4 patients
      (thoracotomy in 2 patients and video-assisted thoracoscopy in 2 patients).
      RESULTS: There were no technical problems during the perfusion period. The
      systemic temperature rose to a maximum of 38 degrees C. There was no renal or
      hematologic toxicity, except in one patient who experienced thrombocytopenia. One
      patient died from complications related to a technical error. Eight patients had
      complications; the most bothersome were in four patients with empyema (early in
      two patients and late in two patients). The median postoperative hospital stay
      was 7 days (range, 2-50 days). Ten patients were alive 28-69 months after
      surgery. The overall 1-year, 2-year, and 3-year survival rates were 72%, 65%, and
      44%, respectively. Complete ipsilateral pleuropulmonary control was achieved in
      17 patients (9 patients who are alive and 8 patients who have died). CONCLUSIONS:
      Intraoperative HPP with cisplatin is feasible, easy to perform, and relatively
      safe. This method may offer excellent local control for patients with pleural
      tumors.

PMID- 11596039
TI  - Incidence trends and risk factors of carcinoid tumors: a nationwide epidemiologic
      study from Sweden.
AB  - BACKGROUND: Carcinoids are rare indolent neuroendocrine tumors, mainly located in
      bowel, stomach, and lung. Their etiology is virtually unknown although a family
      history is a minor cause. METHODS: Site specific incidence trends and several
      risk factors of carcinoid tumors were studied based on the nationwide Swedish
      Family-Cancer Database of 10.2 million individuals and their more than 1 million
      tumors. Data on a total of 5184 carcinoid tumors were retrieved from the Cancer
      Registry covering years 1958-1998. RESULTS: The overall age-adjusted incidence
      rates were 2.0 for men and 2.4/100,000 for women in 1983-1998. Appendix was the
      main site for women whereas small intestine was the main site for men. The
      incidence of all carcinoids, including those at the main sites increased during
      the follow-up period but appeared to plateau in the middle of the 1980s.
      Appendiceal carcinoids showed an unusually early onset with a maximum incidence
      at age 15-19 years for women and 20-29 years for men. Among women, parity was not
      related to the age specific incidence of carcinoid tumors. A Poisson regression
      analysis showed that family history of carcinoids in first-degree relatives
      (relative risk, 3.6), well educated social background (relative risk for
      professionals, 2.8), and birth in large cities were risk factors. CONCLUSIONS:
      The data suggest that the increase in carcinoid tumors may be largely ascribed to
      the application of advanced medical viewing techniques that detect asymptomatic
      tumors. However, the difference in incidence between men and women in appendiceal
      tumor may be real and independent of parity.

PMID- 11596040
TI  - Conditional median survival of patients with advanced carcinoma: surveillance,
      epidemiology, and end results data.
AB  - BACKGROUND: Conditional survival is clinically useful, particularly for patients
      with malignant disease who have a poor prognosis. However, there are no published
      data on the conditional median survival of patients with advanced carcinoma on a
      population basis. METHODS: Data on 217,573 patients with breast, colorectal,
      lung, or prostate carcinoma who were newly diagnosed with distant disease between
      1973 and 1995 and who were followed through the end of 1997 were extracted from
      the Surveillance, Epidemiology, and End Results (SEER) data base of the National
      Cancer Institute. The Kaplan-Meier method was employed to estimate conditional
      median survival and 95% confidence intervals at 0-5 years after the initial
      diagnosis. RESULTS: The conditional median survival increased as time elapsed
      after the initial diagnosis. The increase was slowest and almost leveled off
      among patients with prostate carcinoma. The median survival of patients with
      breast carcinoma increased relatively linearly with time, i.e., 5-6 months per
      year. Conversely, there was a rapid increase in the conditional median survival
      according to the amount of time since diagnosis for patients with lung and
      colorectal carcinoma. The trend was most pronounced for patients with colorectal
      carcinoma. At 5 years after the initial diagnosis, the remaining median survival
      was longest for patients with colorectal carcinoma, almost 6 years (71.5 months),
      followed by patients with lung carcinoma (52.5 months), breast carcinoma (42.5
      months), and prostate carcinoma (34.5 months). Although race was a correlate with
      initial survival, gender and age had more impact on late conditional survival.
      CONCLUSIONS: The conditional median survival provides useful and encouraging
      information for patients who survive with advanced disease and for healthcare
      professionals who treat these patients. However, the information should be used
      carefully, taking the limitations of these data into account.

PMID- 11596041
TI  - Biased methods for estimating local and distant failure rates in breast carcinoma
      and a "commonsense" approach.
AB  - BACKGROUND: Several methods are used to estimate risks of local and distant
      failure after treatment of breast carcinoma. The authors' purpose was to present
      a physician-friendly description of the potential bias in these methods, and to
      suggest an improvement. METHODS: The cumulative incidence based on first event
      (cumulative incidence [CI]) and Kaplan-Meier method based on first (KM[1st]) or
      all (KM[any]) events, are applied to a database comprising 2521 women treated for
      breast carcinoma at the same institution and observed for more than 20 years. The
      authors relate these estimates to the region containing all possible estimates of
      failure rate. This region contains the "true" risk (net risk, or risk that would
      be observed in the absence of competing risks) of local or distant failure.
      RESULTS: The CI estimate is the lowest possible estimate of the true failure
      rate. Under certain "commonsense" assumptions, the CI estimate is below the
      lowest possible estimate of risk of failure. The KM(1st) estimate is higher than
      the CI estimate and lower than the KM(any) estimate. Under the same commonsense
      assumptions, the KM(1st) method also underestimates the true failure rate.
      CONCLUSIONS: Methods based on time to first event such as CI and KM(1st)
      underestimate the true risk. In the design of clinical trials, consideration
      should be given to longer follow-up and the KM(any) method of analyzing results
      because it provides a less biased estimate.

PMID- 11596042
TI  - Lymphatic vessel invasion is an independent prognostic factor in patients with a
      primary resected tumor with esophageal squamous cell carcinoma.
AB  - BACKGROUND: Little data exist about the prognostic role of a lymphatic vessel
      invasion (LVI) in patients with esophageal carcinoma. The objective of this study
      was to clarify the presence and prognostic impact of LVI in a large group of
      patients resected for esophageal squamous cell carcinoma (SCC) at one surgical
      center. METHODS: Three hundred sixty-six patients, who had a primary resection
      for SCC, were analyzed by univariate and multivariate analysis. Follow-up was
      complete for 93.7% patients with a median follow-up of 8.3 years. RESULTS: The
      total rate of LVI was 39.1% (n = 143). Univariate analysis revealed a significant
      relation between LVI and different T classifications (P = 0.001), N
      classifications (P < 0.0001), M classifications (P < 0.0001), International Union
      Against Cancer (UICC) stages (P < 0.0001), and residual tumor (P < 0.0001).
      Multivariate analysis of the patients with R0-resected tumors proved LVI as an
      independent prognostic factor. The 2-, 5- and 10-year survival rates in patients
      with LVI were 28.5%, 11.1%, and 9.2% compared with 63.4%, 46.6%, and 27%,
      respectively, without LVI (P < 0.0001). Patients with LVI had a median survival
      time of 11.4 months compared with 28.6 months without LVI (P < 0.0001). Patients
      with R0-resected tumors without LVI had a median survival time of 54.1 months
      compared with 12.1 months in patients with LVI (P < 0.0001) and compared with
      11.3 months in patients with R1-resected tumors P < 0.0001). CONCLUSIONS: These
      data clearly show that LVI is an independent prognostic factor in patients with
      SCC and confirm the importance of a systematic pathohistologic workup. The
      prognosis of patients with R0-resected tumors with LVI is equal to patients with
      an incomplete tumor resection. This supports the inclusion of LVI in the UICC
      classification system for esophageal carcinoma.

PMID- 11596043
TI  - Nerve injury proximal or distal to the DRG induces similar spinal glial
      activation and selective cytokine expression but differential behavioral
      responses to pharmacologic treatment.
AB  - The specific mechanisms by which nervous system injury becomes a chronic pain
      state remain undetermined. Historically, it has been believed that injuries
      proximal or distal to the dorsal root ganglion (DRG) produce distinct pathologies
      that manifest in different severity of symptoms. This study investigated the role
      of injury site relative to the DRG in (1) eliciting behavioral responses, (2)
      inducing spinal neuroimmune activation, and (3) responding to pharmacologic
      interventions. Rats received either an L5 spinal nerve transection distal to the
      DRG or an L5 nerve root injury proximal to the DRG. Comparative studies assessed
      behavioral nociceptive responses, spinal cytokine mRNA and protein expression,
      and glial activation after injury. In separate studies, intrathecal pharmacologic
      interventions by using selective cytokine antagonists (interleukin-1 [IL-1]
      receptor antagonist and soluble tumor necrosis factor [TNF] receptor) and a
      global immunosuppressant (leflunomide) were performed to determine their relative
      effectiveness in these injury paradigms. Behavioral responses assessed by
      mechanical allodynia and thermal hyperalgesia were almost identical in the two
      models of persistent pain, suggesting that behavioral testing may not be a
      sensitive measure of injury. Spinal IL-1beta, IL-6, IL-10, and TNF mRNA and IL-6
      protein were significantly elevated in both injuries. The overall magnitude of
      expression and temporal patterns were similar in both models of injury. The
      degree of microglial and astrocytic activation in the L5 spinal cord was also
      similar for both injuries. In contrast, the pharmacologic treatments were more
      effective in alleviating mechanical allodynia for peripheral nerve injury than
      nerve root injury, suggesting that nerve root injury elicits a more robust,
      centrally mediated response than peripheral nerve injury. Overall, these data
      implicate alternate nociceptive mechanisms in these anatomically different
      injuries that are not distinguished by behavioral testing or the neuroimmune
      markers used in this study.

PMID- 11596045
TI  - Selective Purkinje cell ectopia in the cerebellum of the weaver mouse.
AB  - The adult mouse cerebellar vermis consists of four transverse zones, each of
      which is further subdivided into parasagittal stripes. In the adult weaver
      (wv/wv) mouse, the zebrin II expression pattern in the cerebellar vermis is
      abnormal, consistent with the absence of a central zone (approximately lobules
      VI/VII). Because the small, heat shock protein HSP25 is a constitutive marker of
      parasagittal bands of Purkinje cells in the caudal central zone and the nodular
      zone (approximately lobules IX/X), we used HSP25 immunocytochemistry to show that
      the patterning abnormalities in wv/wv reflect selective Purkinje cell ectopia
      rather than the absence of the central zone. A specific HSP25-immunopositive
      Purkinje cell ectopia within the central zone was identified. Symmetrical
      clusters of HSP25-immunopositive Purkinje cells, which presumably would have
      formed the parasagittal stripes in the wild type, are present ectopically on
      either side of the midline in wv/wv. In contrast, in the nodular zone, HSP25
      immunopositive Purkinje cells form a near-monolayer and are organized into
      parasagittal stripes. We therefore conclude that specific Purkinje cell clusters
      in the wv/wv cerebellum fail to disperse and that this ectopia contributes to the
      topographical abnormalities.

PMID- 11596044
TI  - Diurnal and circadian variation of protein kinase C immunoreactivity in the rat
      retina.
AB  - We studied the dependence of the expression of protein kinase C immunoreactivity
      (PKC-IR) in the rat retina on the light:dark (LD) cycle and on circadian
      rhythmicity in complete darkness (DD). Two anti-PKC alpha antibodies were
      employed: One, which we call PKCalphabeta recognized the hinge region; the other,
      here termed PKCalpha, recognized the regulatory region of the molecule. Western
      blots showed that both anti-PKC antibodies stained an identical single band at
      approximately 80 kD. The retinal neurons showing PKC-IR were rod bipolar cells
      and a variety of amacrine neurons. After 3 weeks on an LD cycle, PKCalphabeta-IR
      in both rod bipolar and certain amacrine cells manifested a clear rhythm with a
      peak at zeitgeber time (ZT) of 06-10 hours and a minimum at ZT 18. No rhythm in
      total PKC-IR was observed when using the PKCalpha antibody, but, at ZT 06-10
      hours, rod bipolar axon terminals showed increased immunostaining. After 48 hours
      in DD, with either antibody, rod bipolar cells showed increased PKC-IR. The
      PKCalpha antibody alone revealed that, after 48 hours, AII amacrine neurons,
      which lacked PKC-IR in an LD cycle, manifested marked PKC-IR, which became
      stronger after 72 hours. Light administered early in the dark period greatly
      increased PKCalphabeta-IR in rod bipolar and some amacrine neurons. Our data
      indicate that light and darkness exert a strong regulatory influence on PKC
      synthesis, activation, and transport in retinal neurons.

PMID- 11596046
TI  - Two types of projection neurons in the internal pallidum of primates: single-axon
      tracing and three-dimensional reconstruction.
AB  - The axonal projections of the internal pallidum (GPi) in cynomolgus monkeys
      (Macaca fascicularis) were studied by labeling small pools of neurons with
      biotinylated dextran amine. Fifty-two axons were reconstructed entirely from
      serial sections with a camera lucida. Two types of projection neurons were
      identified in the GPi on the basis of their target sites. The abundant and
      centrally located type I neurons gave rise to a long axonal branch that descended
      directly to the pedunculopontine tegmental nucleus, where it arborized
      discretely. Other branches ascended to the thalamus and broke into 10-15 thinner
      collaterals that ran through most of the ventral anterior nucleus, where they
      terminated as typical plexuses. About half of these axons gave rise to
      collaterals that arborized in both components of the centre median/parafascicular
      thalamic complex. The less numerous and peripherally located type II neurons had
      an axon that climbed the rostral thalamic pole, coursed along the stria
      medullaris, and arborized profusely within the lateral habenular nucleus, which
      stood out as the most densely innervated pallidal target. Some type II axons
      provided collaterals to the anterior thalamic nuclei. A small proportion of axons
      of both types had branches that crossed the midline and terminated in
      contralateral GPi target structures. Three-dimensional reconstruction showed that
      type I axons arborized principally along the sagittal plane. These data reveal
      that GPi neurons of type I act through a widely distributed axonal network upon
      thalamic and brainstem premotor neurons, whereas type II neurons act in a much
      more focused manner upon lateral habenular neurons.

PMID- 11596047
TI  - GABAergic neurons that pioneer hippocampal area CA1 of the mouse: morphologic
      features and multiple fates.
AB  - Dramatic changes occur in the expression of glutamic acid decarboxylase (GAD67)
      immunoreactivity in mouse hippocampus during postnatal development. Most striking
      is the presence of a dense population of immunopositive cells in stratum radiatum
      and stratum oriens in area CA1 during the first postnatal week. Between days 5
      and 10, these cells disappear and the GAD67 immunoreactivity begins to resemble
      that of adulthood. These neurons are considered pioneer cells, and studies were
      undertaken to determine their fate. Between days 5 and 50, area CA1 doubles in
      size; however, the loss of cells expressing GAD67 mRNA cannot be explained solely
      by dilution resulting from hippocampal growth. In stratum radiatum, cell loss is
      particularly dramatic. Although between days 5 and 15, many cells seem to migrate
      from stratum radiatum to its border with stratum lacunosum-moleculare, both fate
      maps of pioneer cells labeled with bromodeoxyuridine (BrdU) on embryonic day 13
      (E13) and in situ DNA end-labeling studies suggest that some cells die by means
      of programmed cell death. However, not all pioneer cells die, because many cells
      labeled with BrdU on E13 are present in adulthood and express markers for and
      have anatomic features of hippocampal interneurons. In conclusion, events that
      underlie the age-dependent disappearance of gamma-aminobutyric acid (GABA) -ergic
      pioneer cells are complex and cannot be completely explained by dilution in an
      expanding neuropile. Although some GABAergic pioneer cells likely undergo
      programmed cell death during the first postnatal weeks, others relocate within
      hippocampal laminae and terminally differentiate into the interneurons of
      adulthood.

PMID- 11596048
TI  - Anatomy and physiology of neurons with processes in the accessory medulla of the
      cockroach Leucophaea maderae.
AB  - The accessory medulla (AMe), a small neuropil in the insect optic lobe, has been
      proposed to serve a circadian pacemaker function analogous to the role of the
      suprachiasmatic nucleus in mammals. Building upon considerable knowledge of the
      circadian system of the cockroach Leucophaea maderae, we investigated the
      properties of AMe neurons in this insect with intracellular recordings combined
      with dye injections. Responses of neurons with processes in the AMe to visual
      stimuli, including stationary white light, moving objects, and polarized light
      were compared with the responses of adjacent medulla tangential neurons. Neurons
      with processes in the AMe and additional ramifications in the medulla strongly
      responded to stationary light stimuli and might, therefore, be part of photic
      entrainment pathways to the clock. Accessory medulla neurons lacking significant
      processes in the medulla but with projections to the midbrain or to the
      contralateral optic lobe, in contrast, responded weakly or not at all to light
      and, thus, seem to be part of the clock's output pathway. Two types of
      commissural neurons with tangential arborizations in both medullae were sensitive
      to polarized light, suggesting a role of these neurons in celestial navigation.
      Sidebranches in the AMae of one of the two cell types are discussed with respect
      to a possible involvement of the AMe in polarization vision. Finally, neurons
      responding to movement stimuli did not arborize in the AMe. The results show that
      the AMe receives photic input and support a role of this neuropil in circadian
      timekeeping functions.

PMID- 11596049
TI  - Anatomic relationships between aromatase and androgen receptor mRNA expression in
      the hypothalamus and amygdala of adult male cynomolgus monkeys.
AB  - This study mapped the regional locations of cells expressing cytochrome P450
      aromatase (P450AROM) and androgen receptor (AR) mRNAs in the adult male macaque
      hypothalamus and amygdala by in situ hybridization histochemistry using monkey
      specific cRNA probes. High densities of P450AROM and AR mRNA-containing neurons
      were observed in discrete hypothalamic areas involved in the regulation of
      gonadotropin secretion and reproductive behavior. P450AROM mRNA-containing
      neurons were most abundant in the medial preoptic nucleus, bed nucleus of the
      stria terminalis, and anterior hypothalamic area, whereas AR mRNA-containing
      neurons were most numerous in the ventromedial nucleus, arcuate nucleus, and
      tuberomamillary nucleus. Moderate to heavily labeled P450AROM mRNA-containing
      cells were present in the cortical and medial amygdaloid nuclei, which are known
      to have strong reciprocal inputs with the hypothalamus. Heavily labeled P450AROM
      mRNA-containing cells were found in the accessory basal amygdala nucleus, which
      projects to the cingulate cortex and hippocampus, areas that are important in the
      expression of emotional behaviors and memory processing. In contrast to P450AROM,
      the highest density of AR mRNA labeling in the temporal lobe was associated with
      the cortical amygdaloid nucleus and the pyramidal cells of the hippocampus. All
      areas that contained P450AROM mRNA-expressing cells also contained AR mRNA
      expressing cells, but there were areas in which AR mRNA was expressed but not
      P450AROM mRNA. The apparent relative differences in the expression of P450AROM
      and AR mRNA-containing neurons within the monkey brain suggests that T acts
      through different signaling pathways in specific brain areas or within different
      cells from the same region.

PMID- 11596050
TI  - Localization of the presynaptic cytomatrix protein Piccolo at ribbon and
      conventional synapses in the rat retina: comparison with Bassoon.
AB  - In recent years significant progress has been made in the elucidation of the
      molecular assembly of the postsynaptic density at synapses, whereas little is
      known as yet about the components of the presynaptic active zone. Piccolo and
      Bassoon, two structurally related presynaptic cytomatrix proteins, are highly
      concentrated at the active zones of both excitatory and inhibitory synapses in
      rat brain. In this study we used immunocytochemistry to examine the cellular and
      ultrastructural localization of Piccolo at synapses in the rat retina and
      compared it with that of Bassoon. Both proteins showed strong punctate
      immunofluorescence in the outer and the inner plexiform layers of the retina.
      They were found presynaptically at glutamatergic ribbon synapses and at
      conventional GABAergic and glycinergic synapses. Although the two proteins were
      coexpressed at all photoreceptor ribbon synapses and at some conventional
      amacrine cell synapses, at bipolar cell ribbon synapses only Piccolo was present.
      Our data demonstrate similarities but also differences in the molecular
      composition of the presynaptic apparatuses of the synapses in the retina,
      differences that may account for the functional differences observed between the
      ribbon and the conventional amacrine cell synapses and between the photoreceptor
      and the bipolar cell ribbon synapses in the retina.

PMID- 11596051
TI  - Presynaptic localisation of the nicotinic acetylcholine receptor beta2 subunit
      immunoreactivity in rat nigrostriatal dopaminergic neurones.
AB  - Nicotinic acetylcholine receptors (nAChR) are widely distributed in the central
      nervous system, where they exert a modulatory influence on synaptic transmission.
      For the striatum, pharmacological evidence supports the presence of presynaptic
      alpha3beta2* and alpha4beta2* nAChR that modulate dopamine release from
      nigrostriatal terminals. The objective of this study was to examine the precise
      subcellular distribution of the nAChR beta2 subunit in these neurones and its
      localisation at presynaptic sites. Double immunolabelling with tyrosine
      hydroxylase (TH) at the confocal level revealed that the cell bodies and axon
      terminals (synaptosomes) of nigrostriatal neurones were also immunoreactive for
      the nAChR beta2 subunit. Double-preembedding electron microscopy confirmed that
      beta2-immunogold labelling was enriched in TH-positive terminals in the dorsal
      striatum. Quantitative analysis of doubly immunogold-labelled sections in
      postembedding electron microscopy showed that 86% of TH-positive axonal boutons
      are also labelled for the nAChR beta2 subunit, whereas 45% of beta2 subunit
      immunolabeled boutons do not contain TH. Thus the beta2 subunit is localised
      within at least two populations of axon terminals in the dorsal striatum. In
      these structures, 15% of beta2 subunit immunoreactivity was at the plasma
      membrane but was rarely associated with synapses. These findings are compatible
      with functional presynaptic beta2-containing nAChR that may be stimulated
      physiologically by acetylcholine that diffuses from synaptic or nonsynaptic sites
      of acetylcholine release. These results demonstrate the presynaptic localisation
      of an nAChR subunit in nigrostriatal dopaminergic neurones, providing
      morphological evidence for the presynaptic nicotinic modulation of dopamine
      release.

PMID- 11596052
TI  - Anatomical and functional connections among cell groups in the gerbil brain that
      are activated with ejaculation.
AB  - Based on Fos expression, four areas of the gerbil brain are activated with
      ejaculation, i.e., the posterodorsal preoptic nucleus (PdPN), the lateral part of
      the posterodorsal medial amygdala (MeApd), the medial cell group of the sexually
      dimorphic preoptic area (medial SDA), and the parvicellular part of the
      subparafascicular thalamus (SPFp). The SPFp and medial SDA also express Fos
      earlier in the context of mating. To study connections among these areas, we
      injected one with FluoroGold and assessed the colocalization of FluoroGold and
      mating-induced Fos in the others. To determine if any of these areas activates
      the others, we lesioned one unilaterally and measured mating-induced Fos
      ipsilaterally and contralaterally in the others. Half of the SPFp cells
      projecting to the medial SDA, PdPN, and MeApd were activated with mating. SPFp
      lesions also decreased Fos expression in those areas. However, those areas do not
      project to the SPFp or affect its Fos expression with mating. Projections from
      the lateral MeApd to the medial SDA and PdPN, and from the medial SDA to the
      lateral MeApd, were also activated with mating, but lesions in these areas did
      not affect Fos expression in the others. Because 32-50% of the mating-activated
      cells in the SPFp participated in each SPFp projection identified, projections
      may have been identified for all of the mating-activated cells in the SPFp. In
      contrast, most of the mating-activated cells in the lateral MeApd, PdPN, and
      medial SDA do not participate in any projection studied, suggesting that they are
      either interneurons or project elsewhere.

PMID- 11596053
TI  - Pericellular Griffonia simplicifolia I isolectin B4-binding ring structures in
      the dorsal root ganglia following peripheral nerve injury in rats.
AB  - Patients with a peripheral nerve injury often suffer from persistent chronic
      pain, but the underlying mechanism remains largely unknown. The persistent nature
      of the pain suggests injury-induced profound structural changes along the sensory
      pathways. In the present study, using the plant Griffonia simplicifolia I
      isolectin B4 (IB4) as a marker for nonpeptidergic small sensory neurons, we
      sought to examine whether these neurons sprout in the dorsal root ganglia (DRG)
      in response to peripheral nerve injury. The lumbar 5 (L5) spinal nerve was
      transected, and rats were allowed to survive for varying lengths of time before
      IB4 histology was performed. We found that a subpopulation of IB4-positive
      sensory neurons sprouted robustly after spinal nerve injury. Twelve weeks after
      spinal nerve injury, the IB4-positive ring structures became dramatic and
      encircled both large and small neurons in the DRG. The aberrant sprouting of
      small sensory neurons was also demonstrated by retrograde labeling. The processes
      of satellite cells surrounding large sensory neurons also became IB4 positive,
      and 87.8% of perineuronal IB4-positive ring structures intermingled and/or
      coexpressed with glial fibrillary acidic protein-positive satellite cells. Thus,
      the sprouting axons of IB4-positive neurons were intermingled with IB4-positive
      satellite cells, forming perineuronal ring structures surrounding large-diameter
      neurons. Ultrastructural examinations further confirmed that IB4-positive nerve
      terminals were entangled with satellite cells and IB4-negative unmyelinated
      sprouting fibers around sensory neurons. These studies have provided the first
      evidence that a subpopulation of IB4-binding small sensory neurons sprouts and
      forms perineuronal ring structures together with IB4-positive satellite cells in
      response to nerve injury. The significance of the sprouting of IB4-positive
      neurons remains to be determined.

PMID- 11596054
TI  - Branchiogenic motoneurons innervating facial, masticatory, and esophageal muscles
      show aberrant distribution in the reeler-phenotype mutant rat, Shaking Rat
      Kawasaki.
AB  - Shaking Rat Kawasaki (SRK) is an autosomal recessive mutant rat that is
      characterized by cerebellar ataxia. Although previous studies indicated many
      points of similarity between this mutant rat and the reeler mouse, nonlaminated
      structures such as the facial nucleus have not been studied in this mutant rat.
      Nissl-stained sections through the brainstem showed that the cytoarchitecture of
      the facial, motor trigeminal, and ambiguus nuclei was abnormal in SRK, especially
      in the lateral cell group of the facial nucleus and the compact formation of the
      ambiguus nucleus. To examine whether orofacial motoneurons are also malpositioned
      in the SRK rat, horseradish peroxidase (HRP) was injected into the facial,
      masticatory, and abdominal esophageal muscles of the SRK rats and normal controls
      to label facial, trigeminal, and ambiguus motoneurons, respectively. HRP-labeled
      facial, trigeminal, and ambiguus motoneurons of the SRK rat were distributed more
      widely than those of their normal counterparts, as in the case of the reeler
      mouse, with the one exception that labeled facial motoneurons innervating the
      nasolabial muscle were distributed more widely in the ventrolateral-to
      dorsomedial direction in comparison with those of the reeler mutant. These data
      demonstrate that nonlaminated structures in the brainstem of the SRK rat are
      affected severely, as is the case in the reeler mutant mouse.

PMID- 11596055
TI  - Activity and localization of 3beta-hydroxysteroid dehydrogenase/ Delta5-Delta4
      isomerase in the zebrafish central nervous system.
AB  - Little information is available for neurosteroidogenesis in the central nervous
      system (CNS) of lower vertebrates. Therefore, in the present study, we examined
      the enzymatic activity and localization of 3beta-hydroxysteroid
      dehydrogenase/Delta5-Delta4-isomerase (3betaHSD), a key steroidogenic enzyme, in
      the CNS of adult male zebrafish to clarify central progesterone biosynthesis.
      Biochemical studies together with HPLC analysis revealed that the zebrafish brain
      converted pregnenolone to progesterone, suggesting the enzymatic activity of
      3betaHSD. This conversion was significantly reduced by trilostane, a specific
      inhibitor of 3betaHSD. By using Western immunoblotting with the polyclonal
      antiserum directed against purified bovine adrenal 3betaHSD, a 3betaHSD-like
      substance was found in homogenates of the zebrafish brain. Immunocytochemical
      analysis was then undertaken to investigate the localization of the 3betaHSD-like
      substance in the zebrafish brain and spinal cord. Clusters of immunoreactive cell
      bodies were localized in the dorsal telencephalic areas (D), central posterior
      thalamic nucleus (CP), preoptic nuclei (NPO), posterior tuberal nucleus (PTN),
      paraventricular organ (PVO), and nucleus of medial longitudinal fascicle (NMLF).
      3betaHSD-like immunoreactivity was also observed in somata of cerebellar Purkinje
      neurons. A widespread distribution of immunoreactive fibers was found throughout
      the brain and spinal cord. In addition, positively stained cells were restricted
      to other organs, such as the pituitary and retina. Preabsorbing the antiserum
      with purified bovine adrenal microsome resulted in a complete absence of 3betaHSD
      like immunoreactivity. These results suggest that the fish CNS possesses
      steroidogenic enzyme 3betaHSD and produces progesterone. The present study
      further provides the first immunocytochemical mapping of the site of 3betaHSD
      expression in the fish CNS.

PMID- 11596056
TI  - Fos-like immunohistochemical identification of neurons active during the startle
      response of the rainbow trout.
AB  - Activity-dependent Fos-like expression was investigated immunohistochemically in
      rainbow trout (Oncorhynchus mykiss) that had performed vibratory-evoked startle
      responses. We found significantly higher numbers of Fos-like-immunoreactive
      neurons in the reticular formation, in the octavolateral area, and in several
      cranial nerve motor nuclei in the brain and in the motor column of the spinal
      cord of startled fish than in control fish. In one fish, in which stimulation did
      not evoke startle responses, substantial numbers of positive cells occurred in
      the brain, primarily in the magnocellular octavolateral nucleus. We observed Fos
      like-immunoreactive neurons in cell groups that are known to participate in the
      startle response (e.g., the Mauthner cell) as well as in cell groups that have
      been proposed but until now not shown to be involved.

PMID- 11596057
TI  - Identification of sequence, protein isoforms, and distribution of the hyaluronan
      binding protein RHAMM in adult and developing rat brain.
AB  - The protein RHAMM (for "receptor for hyaluronan-mediated motility"; CD168) is a
      member of the hyaladherin family of hyaluronan-binding proteins. RHAMM has a role
      in cell signaling, migration, and adhesion via interactions with hyaluronan,
      microtubules, actin, calmodulin, and components of the extracellular regulated
      kinase (erk) signaling pathway. Based on previous findings of potentially similar
      roles in neural cells in culture, we investigated the molecular characteristics,
      protein expression profile, and distribution of RHAMM in rat brain. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) using RNA isolated from adult
      rat brain yielded a single RHAMM sequence of 2.1 kilobases encoding a protein of
      82.4 kDa. RHAMM is subject to alternate splicing in other systems, but no RT-PCR
      evidence was found for splice variants in brain, although our analysis does not
      rule out this possibility. The amino acid sequence displayed homology with human
      and murine RHAMM (74% and 80%, respectively) but contained only one copy of a 21
      amino-acid sequence that is repeated five times in the murine homologue. By using
      anti-RHAMM antibodies, several RHAMM isoforms were identified in brain.
      Immunohistochemically, RHAMM was found in the vast majority of neurons and in
      many oligodendrocytes throughout brain, with heterogeneous levels among cell
      populations, and was confined to the somata and initial processes of these cells.
      RHAMM was detected in neurons of cerebral cortex and most subcortical and
      brainstem structures at postnatal day 1 and exhibited an adult distribution
      pattern by postnatal day 5. High levels were detected in oligodendrocytes by
      postnatal day 10. The widespread expression of RHAMM in adult and developing
      brain implies a role for this protein and its ligand hyaluronan in key events of
      cell signaling and cytoskeletal regulation in the CNS.

PMID- 11596059
TI  - Taurine-, aspartate- and glutamate-like immunoreactivity identifies chemically
      distinct subdivisions of Kenyon cells in the cockroach mushroom body.
AB  - The lobes of the mushroom bodies of the cockroach Periplaneta americana consist
      of longitudinal modules called laminae. These comprise repeating arrangements of
      Kenyon cell axons, which like their dendrites and perikarya have an affinity to
      one of three antisera: to taurine, aspartate, or glutamate. Taurine
      immunopositive laminae alternate with immunonegative ones. Aspartate
      immunopositive Kenyon cell axons are distributed across the lobes. However,
      smaller leaf-like ensembles of axons that reveal particularly high affinities to
      anti-aspartate are embedded within taurine-positive laminae and occur in the
      immunonegative laminae between them. Together, these arrangements reveal a
      complex architecture of repeating subunits whose different levels of
      immunoreactivity correspond to broader immunoreactive layers identified by sera
      against the neuromodulator FMRFamide. Throughout development and in the adult,
      the most posterior lamina is glutamate immunopositive. Its axons arise from the
      most recently born Kenyon cells that in the adult retain their juvenile
      character, sending a dense system of collaterals to the front of the lobes.
      Glutamate-positive processes intersect aspartate- and taurine-immunopositive
      laminae and are disposed such that they might play important roles in
      synaptogenesis or synapse modification. Glutamate immunoreactivity is not seen in
      older, mature axons, indicating that Kenyon cells show plasticity of
      neurotransmitter phenotype during development. Aspartate may be a universal
      transmitter substance throughout the lobes. High levels of taurine
      immunoreactivity occur in broad laminae containing the high concentrations of
      synaptic vesicles.

PMID- 11596058
TI  - Development of laminar organization in the mushroom bodies of the cockroach:
      Kenyon cell proliferation, outgrowth, and maturation.
AB  - The mushroom bodies of the insect brain are lobed integration centers made up of
      tens of thousands of parallel-projecting axons of intrinsic (Kenyon) cells. Most
      of the axons in the medial and vertical lobes of adult cockroach mushroom bodies
      derive from class I Kenyon cells and are organized into regular, alternating
      pairs (doublets) of pale and dark laminae. Organization of Kenyon cell axons into
      the adult pattern of laminae occurs gradually over the course of nymphal
      development. Newly hatched nymphs possess tiny mushroom bodies with lobes
      containing a posterior lamina of ingrowing axons, followed by a single doublet,
      which is flanked anteriorly by a gamma layer composed of class II Kenyon cells.
      Golgi impregnations show that throughout nymphal development, regardless of the
      number of doublets present, the most posterior lamina serves as the "ingrowth
      lamina" for axons of newborn Kenyon cells. Axons of the ingrowth lamina are
      taurine- and synaptotagmin-immunonegative. They produce fine growth cone tipped
      filaments and long perpendicularly oriented collaterals along their length. The
      maturation of these Kenyon cells and the formation of a new lamina are marked by
      the loss of filaments and collaterals, as well as the onset of taurine and
      synaptotagmin expression. Class I Kenyon cells thus show plasticity in both
      morphology and transmitter expression during development. In a hemimetabolous
      insect such as the cockroach, juvenile stages are morphologically and
      behaviorally similar to the adult. The mushroom bodies of these insects must be
      functional from hatching onward, while thousands of new neurons are added to the
      existing structure. The observed developmental plasticity may serve as a
      mechanism by which extensive postembryonic development of the mushroom bodies can
      occur without disrupting function. This contrasts with the more evolutionarily
      derived holometabolous insects, such as the honey bee and the fruit fly, in which
      nervous system development is accomplished in a behaviorally simple larval stage
      and a quiescent pupal stage.

PMID- 11596060
TI  - Identification and characterization of a cell surface marker for embryonic rat
      spinal accessory motor neurons.
AB  - The developing mammalian spinal cord contains distinct populations of motor
      neurons that can be distinguished by their cell body positions, by the expression
      of specific combinations of regulatory genes, and by the paths that their axons
      take to exit the central nervous system (CNS). Subclasses of spinal motor neurons
      are also thought to express specific cell surface proteins that function as
      receptors which control the guidance of their axons. We identified monoclonal
      antibody (mAb) SAC1 in a screen aimed at generating markers for specific subsets
      of neurons/axons in the developing rat spinal cord. During early embryogenesis,
      mAb SAC1 selectively labels a small subset of Isl1-positive motor neurons located
      exclusively within cervical segments of the spinal cord. Strikingly, these
      neurons extend mAb SAC1-positive axons along a dorsally directed trajectory
      toward the lateral exit points. Consistent with the finding that mAb SAC1 also
      labels spinal accessory nerves, these observations identify mAb SAC1 as a
      specific marker of spinal accessory motor neurons/axons. During later stages of
      embryogenesis, mAb SAC1 is transiently expressed on both dorsally and ventrally
      projecting spinal motor neurons/axons. Interestingly, mAb SAC1 also labels the
      notochord and floor plate during most stages of spinal cord development. The mAb
      SAC1 antigen is a 100-kD glycoprotein that is likely to be the rat homolog of
      SC1/BEN/DM-GRASP, a homophilic adhesion molecule that mediates axon outgrowth and
      fasciculation.

PMID- 11596061
TI  - Relationship between insult intensity and mode of hair cell loss in the
      vestibular system of rats exposed to 3,3'-iminodipropionitrile.
AB  - A variety of stimuli cause sensory hair cell loss in the mammalian inner ear.
      This loss occurs by several differing processes, the significance of which
      remains undetermined. This study examines the relationship between the intensity
      of the damaging stimulus and the mode of hair cell loss found in the vestibular
      sensory epithelia of the rat. The ototoxin 3,3'-iminodipropionitrile (IDPN) was
      administered to rats at three different intoxication rates: acute exposure to
      high doses, repeated exposure to intermediate doses, and subchronic exposure to
      low doses. The morphology of the vestibular epithelia was examined by light
      microscopy and by scanning and transmission electron microscopy (SEM and TEM). In
      addition, DNA fragmentation in the epithelia was assessed by terminal
      deoxynucleotidyl transferase (tdt)-dUTP-nick-end-label (TUNEL). One day after
      acute IDPN, necrosis of hair cells was observed. However, at day 4 with this
      dose, and 1 and 4 days after repeated exposure, apoptotic figures and positive
      TUNEL labeling predominated. Subchronic IDPN resulted in a slowly evolving
      extrusion of basically intact hair cells in the crista and utricle. The data
      demonstrate that extrusion is a major mechanism of hair cell demise in mammals,
      that necrosis, apoptosis, and extrusion form a continuum of modes of hair cell
      loss, and that the intensity of the damaging stimulus determines the prevalence
      of each mode: Necrosis was most evident when the intensity was at its highest,
      whereas extrusion predominated when the intensity was at the lowest end of the
      scale.

PMID- 11596062
TI  - Identification of a nonmammalian Golf subtype: functional role in olfactory
      signaling of airborne odorants in Xenopus laevis.
AB  - Attempts to identify the Galpha subtypes in the two compartments of the olfactory
      system from Xenopus, which are supposed to be specialized for detecting aquatic
      and volatile odorous compounds, revealed that a Galpha(o1) subtype is
      characteristic for the "water nose," the lateral diverticulum, whereas a novel
      Galpha(s) subtype predominates in the "air nose," the medial diverticulum. The
      newly identified Galpha(s)-type is more closely related to Galpha(olf) of rat and
      human than to the known Galpha(s)-isoform of Xenopus; it is therefore considered
      the first identified nonmammalian Galpha(olf) subtype. Sequence comparison of
      Galpha(olf) from amphibia and mammals revealed a particular conservation within
      the alpha-helical domains, which are supposed to control the GDP/GTP-exchange
      rate. The selective expression of different Galpha subtypes in the two
      anatomically separated and functionally specialized nasal compartments parallels
      the expression of distinct classes of olfactory receptors. Moreover, biochemical
      analysis revealed that stimulation with appropriate odorous compounds elicits the
      formation of inositol trisphosphate in the lateral diverticulum. In contrast,
      cyclic adenosine monophosphate signals were induced in the medial diverticulum,
      and this response appears to be mediated by the novel Galpha(olf) subtype. The
      data indicate that olfactory sensory neurons in each of the nasal cavities are
      equipped not only with defined sets of receptor types but also with a distinct
      molecular machinery for the chemo-electrical transduction process.

PMID- 11596063
TI  - Light and electron microscopic study of cholinergic and noradrenergic elements in
      the basolateral nucleus of the rat amygdala: evidence for interactions between
      the two systems.
AB  - Pharmacological studies have suggested that the cholinergic (ACh) and
      noradrenergic (NA) systems in the amygdala (AM) play an important role in
      learning and memory storage and that the two systems interact to modulate memory
      storage. To obtain anatomical evidence for the interaction, the organization of
      the ACh and NA fibers in rat AM was investigated by immunocytochemistry for
      choline acetyltransferase (ChAT) and dopamine-beta-hydroxylase (DBH) in
      conjunction with light, confocal laser scanning, and electron microscopy (LM,
      CLSM, and TEM, respectively). LM showed that the ChAT immunoreactivity was
      densest in the basolateral nucleus (BL), whereas the DBH immunoreactivity was
      densest in the posterior BL. CLSM demonstrated that the ChAT-immunoreactive
      profiles in the BL were frequently located in juxtaposition to the DBH
      immunoreactive axons. The TEM observations were as follows: The majority of the
      synapses formed by ChAT-immunoreactive terminals were symmetric, but DBH
      immunoreactive axons formed both asymmetric and symmetric synapses. The ChAT
      immunoreactive terminals usually established the symmetric synaptic contacts with
      the DBH-immunoreactive terminals and varicosities. The DBH-immunoreactive
      terminals formed the asymmetric synapses with the ChAT-immunoreactive dendrites
      of the intrinsic neurons within the AM. The results provide anatomical substrates
      for mnemonic functions of the ACh and NA systems and for the interactions between
      the two systems in the AM.

PMID- 11596064
TI  - Physiological and anatomic evidence for functional subclasses of serotonergic
      raphe magnus cells.
AB  - Serotonergic cells in the medullary nucleus raphe magnus (RM) and adjacent
      nucleus reticularis magnocellularis (NRMC) project to the spinal cord where they
      are likely to modulate nociceptive transmission. Previous studies have suggested
      that these cells are physiologically and anatomically heterogeneous. In the
      present investigation, we examined whether subclasses of serotonergic RM and NRMC
      cells can be delineated based on their response to a visceral stimulus, and
      whether any such subclasses are morphologically distinct. Most RM and NRMC
      serotonergic cells tested (81 of 116) responded to retraction of the descending
      aorta into a polyethylene tube (the snare stimulus) with 57% of all cells tested
      excited and 13% inhibited. Responses of serotonergic cells to the snare outlasted
      the stimulus, were not reflective of evoked cardiovascular changes, and were
      observed in sino-aortic deafferented rats, evidence that the snare stimulus does
      not influence serotonergic cell discharge through activation of baroreceptors.
      Because serotonergic cells responsive to the snare were also responsive to
      mechanical brushing within the retroperitoneum, the snare is likely to change
      serotonergic cell discharge by means of the activation of mechanosensitive
      visceral afferents. Intracellular labeling of physiologically characterized
      serotonergic RM and NRMC cells showed that cells that were responsive to the
      snare stimulus had simpler axonal collateralization patterns than cells that were
      unresponsive to the snare stimulus. This association between morphological and
      physiological properties provides additional evidence that subpopulations of
      serotonergic cells exist and serve varied physiological functions.

PMID- 11596065
TI  - Two phases of increased cell death in the inner retina following early
      elimination of the ganglion cell population.
AB  - Neurons in the inner nuclear layer (INL) of the vertebrate retina undergo
      considerable programmed cell death during development, but the determinants of
      this cell death remain largely unknown. The present study examines the role of
      retinal ganglion cells in support of INL neurons in the developing ferret retina.
      The retinal ganglion cell population was eliminated by optic nerve transection at
      postnatal day (P) 2, and the incidence of cell death was examined using terminal
      deoxytransferase dUTP nick-end labelling (TUNEL) at various ages during the first
      3 postnatal weeks. Significant increases in TUNEL-positive cells were observed in
      the neuroblast layer (NBL) as early as P3, prior to synapse formation within the
      inner plexiform layer (IPL), and again in the INL at P22, the normal peak of
      naturally occurring cell death within the ferret's INL. A decrease in TUNEL
      positive cells was found in the NBL at P8. These results show three phases of
      response to the loss of retinal ganglion cells and suggest that cells in the
      NBL/INL are normally dependent on retinal ganglion cells for their survival.
      Recent studies have shown that certain populations of retinal neurons are reduced
      in adult animals that had lost the population of ganglion cells during early
      development, so the present study also examined when this reduction could first
      be detected. The number of parvalbumin-immunoreactive amacrine cells was
      decreased significantly in the NBL of the manipulated eye as early as P8, when we
      could first label this population, and this difference persisted through
      adulthood. The fact that cell death in the NBL has already increased within 24
      hours of ganglion cell elimination, coupled with the specificity of this effect
      on the adult complement of INL cell types, shows that cell-cell interactions
      controlling survival are already highly specific for particular types of retinal
      neuron early in development

PMID- 11596066
TI  - Serotonergic and octopaminergic systems in the squat lobster Munida quadrispina
      (Anomura, Galatheidae).
AB  - Immunocytochemical mapping of serotonergic and octopaminergic neurons in the
      central nervous system of the squat lobster Munida quadrispina reveal
      approximately 120 serotonin-immunoreactive cell bodies (distributed throughout
      the neuromeres except in abdominal ganglion 5) and 48 octopamine-immunoreactive
      cell bodies (in brain and thoracic neuromeres but none in the circumesophageal or
      abdominal ganglia). Immunopositive neuropils for both amines are distributed in
      multiple areas in each neuromere and overlap extensively. Serotonergic and
      octopaminergic neurons have extensive bilateral projections in abdominal ganglia,
      whereas the majority of projections in thoracic and subesophageal ganglia are
      unilateral (contralateral to soma). This difference correlates with typical
      differences between abdominal and thoracic motor system coordination. Processes
      of immunoreactive cells for both amines form extensive, peripheral,
      neurosecretory-like structures. Serotonin seems to be released peripherally in
      more segments, and from more nerves per segment, than octopamine. M. quadrispina
      has fewer serotonergic and octopaminergic immunoreactive cells, in particular,
      fewer segmentally repeated cells, than other species studied to date.
      Nevertheless, the general organization of the aminergic systems is similar, and
      several aminergic cells have locations and morphologies that strongly suggest
      homology with identified aminergic cells in other crustaceans. Among these are
      segmentally repeated neurons that, in M. quadrispina, form serotonin
      immunopositive tubular structures in the thoracic hemiganglia innervating
      pereiopods 1-3 that are unlike anything reported previously for any species.
      Comparisons of immunocytochemical maps within one species and between species
      exhibiting different behaviors provide insights into possible sites of action,
      functional differences between, and evolution of biogenic aminergic systems.

PMID- 11596067
TI  - Corticopulvinar connections of areas V5, V4, and V3 in the macaque monkey: a dual
      model of retinal and cortical topographies.
AB  - The connection zones of cortical areas V3, V4, and V5 (MT) with the thalamic
      pulvinar nucleus in the macaque monkey were identified. A combination of single-
      and dual-tracer techniques was used to study their topography and to establish
      whether these zones occupy separate or overlapping pulvinar territories. In each
      case, the retinotopic distribution of tracer in the pulvinar was charted by
      reference to its parallel distribution within the maps of cortical areas V1 and
      V2. Each of the areas V3, V4, and V5 were found to connect with both the 1
      degrees  and the 2 degrees  maps located within the inferior and lateral pulvinar
      nuclei and to respect the previously identified topographies of these maps.
      However, V5 connects to a narrow zone lining the rostrolateral margin of the
      lateral and inferior pulvinar and V4 to a broader zone within the body of these
      two nuclei, which is adjacent to but separate from the V5 zone; the V3 zone
      overlaps both. Focal injections into cortex produce columns of pulvinar label
      whose trajectory defines a line of isorepresentation. The lines of
      isorepresentation in the 1 degrees  and 2 degrees  maps are approximately linear
      and parallel and adopt a rostrolateral to caudomedial axis; in the 1 degrees 
      map, this axis is roughly perpendicular to the facet of the inferior pulvinar
      that lies adjacent to the lateral geniculate nucleus. The connections of V5 and
      V4 can be modelled as successive zones along the axis of isorepresentation, with
      registered visual topographies. The scheme is extended by existing reports that
      inferotemporal cortex connects to the caudomedial pole of this axis-reflecting an
      occipitotemporal cortical gradient, in that V1 and other prestriate areas, e.g.,
      V3, connect to the opposite pole. Thus a simple model of the mapped volume in the
      pulvinar arises, in which a unidimensional cortical topography is represented
      orthogonally to retinal topography. Adjoining this volume medially, within the
      inferior and medial pulvinar, is a second, heavier zone of V5 connectivity, which
      is poorly topographic. Both the medial and the rostrolateral zones of V5
      connectivity may overlap with previously identified regions of tectal input to
      the pulvinar.

PMID- 11596068
TI  - Presence of luteinizing hormone-releasing hormone fragments in the rhesus monkey
      forebrain.
AB  - Previously, we have shown that two types of luteinizing hormone-releasing hormone
      (LHRH) -like neurons, "early" and "late" cells, were discernible in the forebrain
      of rhesus monkey fetuses by using antiserum GF-6, which cross-reacts with several
      forms of LHRH. The "late" cells that arose from the olfactory placode of monkey
      fetuses at embryonic days (E) 32-E36, are bona fide LHRH neurons. The "early"
      cells were found in the forebrain at E32-E34 and settled in the extrahypothalamic
      area. The molecular form of LHRH in "early" cells differs from "late" cells,
      because "early" cells were not immunopositive with any specific antisera against
      known forms of LHRH. In this study, we investigated the molecular form of LHRH in
      the "early" cells in the nasal regions and brains of 13 monkey fetuses at E35 to
      E78. In situ hybridization studies suggested that both "early" and "late" LHRH
      cells expressed mammalian LHRH mRNA. Furthermore, "early" cells predominantly
      contain LHRH1-5-like peptide and its cleavage enzyme, metalloendopeptidase
      E.C.3.4.24.15 (EP24.15), which cleaves LHRH at the Tyr5-Gly6 position. This
      conclusion was based on immunocytochemical labeling with various antisera,
      including those against LHRH1-5, LHRH4-10, or EP24.15, and on preabsorption
      tests. Therefore, in primates, a group of neurons containing mammalian LHRH mRNA
      arises at an early embryonic stage before the migration of bona fide LHRH
      neurons, and is ultimately distributed in the extrahypothalamic region. These
      extrahypothalamic neurons contain LHRH fragments, rather than fully mature
      mammalian LHRH. The origin and function of these neurons remain to be determined.

PMID- 11596069
TI  - Ernst Mach and the episode of the monocular depth sensations.
AB  - Although Ernst Mach is widely recognized in psychology for his discovery of the
      effects of lateral inhibition in the retina ("Mach Bands"), his contributions to
      the theory of depth perception are not as well known. Mach proposed that steady
      luminance gradients triggered sensations of depth. He also expanded on Ewald
      Hering's hypothesis of "monocular depth sensations," arguing that they were
      subject to the same principle of lateral inhibition as light sensations were.
      Even after Hermann von Helmholtz's attack on Hering in 1866, Mach continued to
      develop theories involving the monocular depth sensations, proposing an
      explanation of perspective drawings in which the mutually inhibiting depth
      sensations scaled to a mean depth. Mach also contemplated a theory of stereopsis
      in which monocular depth perception played the primary role.

PMID- 11596070
TI  - Negotiating illness: doctors, patients, and families in the nineteenth century.
AB  - This article is based on medical literature published in American and British
      monographs and medical journals in which physician-authors utilized case
      histories of women's nervous and mental disease and related gynecological
      complaints. I argue that the interaction of physicians, patients, and families
      was a relationship in which women patients contributed to the formation of
      medical knowledge and forged a modern sense of body and self. After an
      introductory section on reading case studies, I call attention to the ways in
      which physicians, patients, and patients' families educated each other about
      wellness and illness, which formed the basis of physicians' interpretation of
      disease. Next, I point out how the case histories structured an ideal script for
      doctor, patient, and family, based on physicians' sympathetic authority and
      patients' willingness to tell and show all. And finally, I suggest that the
      doctor-patient dialogue encouraged women patients to see themselves as medically
      manageable bodies and as individuals separate from families.

PMID- 11596071
TI  - Divergences in American psychiatry during the Depression: somatic psychiatry,
      community mental hygiene, and social reconstruction.
AB  - The differences between somatic psychiatrists and mental hygienists, already
      apparent earlier, became much more pronounced during the Depression years, partly
      as a consequence of their different perspectives on this social crisis. Somatic
      psychiatrists, emboldened by the apparent success of new medical treatment
      methods, reasserted the central position of the mental hospital within
      psychiatry, attempted to improve the discipline's position within medicine, and
      promoted basic research. Mental hygienists, following the ideal of prevention,
      proposed far-reaching programs of community mental hygiene to alleviate
      widespread mental distress. A small group of mental hygienists embraced socialism
      and advocated measures of radical social reconstruction.

PMID- 11596074
TI  - Modulation of expression of the MHC class I-binding natural killer cell
      receptors, and NK activity in relation to viral load in HIV-infected/AIDS
      patients.
AB  - The natural killer (NK) cells play an important role in viral infections via
      their spontaneous cytolytic activity against virus-infected cells as well as via
      secreting a variety of soluble mediators. The MHC class I-binding NK receptors of
      these cells have emerged as the most important regulators of the effector
      activities of cytolytic cells (both NK and CTL). We have studied the modulation
      of NK activity and the expression of NK receptors in HIV-infected/AIDS patients
      and report here that the NK activities of the patients with the lowest plasma HIV
      load were minimal and vice versa, suggesting a decrease in this activity
      following suppression of HIV replication. Interestingly, the NK activity
      correlated negatively with the peripheral blood CD4+ T-cell counts of these
      patients. Furthermore, these patients showed decreased percentages of CD56+ cells
      expressing NK receptors of the immunoglobulin superfamily, whereas the
      percentages of CD8+ cells expressing these receptors were increased. Moreover,
      the expression of C-type lectin-like NK receptor-associated invariant molecule
      CD94 was increased on CD8+ cells in these patients as compared with HIV
      seronegative controls. These changes in the expression of NK receptors were also
      evident within groups of these patients having different viral loads. These
      results show, for the first time, decreased innate immunity and changes in the
      expression of NK receptors on cytolytic cells in relation to viral burden in HIV
      infected/AIDS patient.

PMID- 11596075
TI  - Adverse effect of the CCR5 promoter -2459A allele on HIV-1 disease progression.
AB  - HIV positive individuals heterozygous for a 32 basepair deletion in the CCR5
      encoding gene (CCR5 Delta32) have a reduced number of CCR5 receptors on the cell
      surface and a slower progression towards AIDS and death. Other human
      polymorphisms, such as the CCR2 64I and the CCR5 promoter -2459 A/G transition
      that has been discovered recently, have also been shown to influence HIV
      progression. Since genetic linkages make these polymorphisms interdependent
      variables, the aim of the present study was to isolate and evaluate the effect on
      HIV disease progression for each of these mutations independently. Genotypes were
      determined in 119 individuals enrolled in the Copenhagen AIDS Cohort. When
      including the concurrent effects of the CCR5 Delta32 and CCR2 64I mutations,
      homozygous carriers of the CCR5 promoter -2459A allele had a significantly faster
      progression towards death than heterozygous A/G individuals (P = 0.03), whereas
      this adverse effect was not significant when comparing A/A and G/G individuals.
      However, independent analysis revealed a significant adverse effect of the CCR5
      promoter -2459A allele. Homozygous carriers of the -2459A allele that lack the
      protective effects of the CCR5 Delta32 and CCR2 64I mutations were found to have
      a median survival of 6.0 years, whereas carriers of the -2459G allele had a
      median survival of 9.4 years (P < 0.01).

PMID- 11596076
TI  - Resistance profile and cross-resistance of HIV-1 among patients failing a non
      nucleoside reverse transcriptase inhibitor-containing regimen.
AB  - The objectives were to determine the resistance profile and the rate of cross
      resistance in HIV-1 infected patients failing an efavirenz or a nevirapine or a
      nevirapine then efavirenz containing regimens, and to investigate if zidovudine
      and more generally thymidine analog nucleosides lead to a particular genotypic
      pattern in nevirapine failing patients. A study was conducted in 104 patients
      with virological rebound to a non-nucleoside reverse transcriptase inhibitors
      (NNRTI) regimen (efavirenz n = 39, nevirapine n = 46 and nevirapine then
      efavirenz n = 19). Genotypic resistance testing was carried out of detectable
      plasma HIV-1 RNA (> 200 copies/ml). Among the 104 patients studied, only two
      patients failed to respond to the nevirapine regimen without selection of a NNRTI
      resistance mutation. All patients failing an efavirenz regimen harboured
      mutations conferring cross-resistance to nevirapine (K103N, Y188L, G190S). Among
      patients failing the nevirapine regimen and presenting with NNRTI mutations, 35
      (80%) harboured mutations conferring cross-resistance to efavirenz (K101E, K103N,
      Y188L) and 9 (20%) harboured mutations conferring resistance to nevirapine alone
      (V106A and Y181C). In patients failing nevirapine then efavirenz therapy, all
      NNRTI resistance profile led to cross-resistance to all available NNRTIs. Among
      patients receiving nevirapine, the selection of mutations associated with a cross
      resistance to efavirenz was more frequent statistically when a thymidine
      nucleoside analog (zidovudine or stavudine) was used in the regimen (P = 0.02).
      In conclusion, 100% of patients developed cross-resistance to nevirapine and
      efavirenz after treatment by efavirenz and 80% after treatment by nevirapine. The
      use of a thymidine analog concomitantly with nevirapine leads to the preferential
      selection of cross-resistance NNRTI mutations.

PMID- 11596078
TI  - Sequence analysis of hepatitis B virus genomes from an infant with acute severe
      hepatitis and a hepatitis B e antigen-positive carrier mother.
AB  - It is well known that fulminant hepatitis B can occur in infants born to
      hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) carrier mothers,
      whereas fulminant hepatitis and severe hepatitis are uncommon in infants born to
      HBeAg-positive mothers. We have encountered an infant with severe acute hepatitis
      B born to a HBeAg-positive mother. The aim of this study was to determine whether
      HBV variants contribute to the pathogenesis of fulminant hepatitis and severe
      hepatitis in an infant born to an HBeAg-positive mother. The nucleotide sequence
      of HBV genomes from the infant and his HBeAg-positive carrier mother was
      analyzed. All HBV isolated from the infant and his mother were subtype adr. The
      sequences of the cloned HBV genomes, each including a part of the X and
      precore/core regions, isolated from the infant were almost identical (homology of
      99.1-99.9%) to those from his mother. There was no mutation in any of the 17
      clones examined at nucleotides 1762 and 1764 in the core promoter, which is
      reported to be associated with fulminant hepatitis. A point mutation at
      nucleotide 1758 in the second AT-rich region of the basic core promoter was
      present in all clones. None of the clones had a point mutation at nucleotide 1896
      of the precore region. In this study, no specific HBV variants contributing to
      the development of neonatal severe hepatitis were found. There is a possibility
      that host factors rather than viral factors play an important role in some cases
      of severe neonatal hepatitis B.

PMID- 11596077
TI  - Presumed common source outbreaks of hepatitis A in an endemic area confirmed by
      limited sequencing within the VP1 region.
AB  - Hepatitis A virus isolates from anti-HAV IgM positive sera of 70 hepatitis cases
      in two outbreaks and 216 other cases in Central America, 136 sporadic cases and
      53 cases from an hyper-endemic region in Costa Rica, were compared by
      phylogenetic analyses within the VP1 region. The outbreaks in all 531 cases, in
      1992 and 1999, respectively, were presumed water borne. In the first outbreak,
      HAV RNA could be detected in 70% of the cases sampled during 6 weeks after onset
      of jaundice. In the hyper-endemic region of San Ramon in Costa Rica, 1,932 cases
      were registered between 1972 and 1985. All isolates belonged to subtype 1A.
      Background isolates from Costa Rica and El Salvador tended to form separate
      subclusters in the phylogenetic tree construction and were mostly unrelated to
      subtype 1A strains from other parts of the world. Based on their amino acid
      sequences, four HAV strains, all related to CR326 sampled in Costa Rica in 1960,
      were found to have circulated in the area during the last three decades. However,
      on the basis of nucleotide variability the isolates from the outbreaks could be
      distinguished from the strains from sporadic cases and sequence analysis could
      confirm the epidemiological homogeneity of both outbreaks. In the hyper-endemic
      region, 16 different sequences were encountered forming one single subcluster.
      Thus, limited sequencing within the VP1 region proved useful to identify
      outbreaks of hepatitis A in a highly endemic area, where most strains were local
      and only one subtype was prevalent.

PMID- 11596079
TI  - Phylogenetic analysis of new hepatitis B virus isolates from Nigeria supports
      endemicity of genotype E in West Africa.
AB  - Isolates of hepatitis B viruses were collected from 20 acute and chronic
      hepatitis patients in a highly endemic region of Nigeria. Sequencing classified
      the isolates to the ayw4, as they all contained the amino acid variations
      characteristic for that serotype. In the pre-S2 region of five isolates, three to
      seven amino acids were deleted, suggesting that immune escape mutations
      previously associated only with chronic HBV infection may be observed also in
      acute disease. Phylogenetic analysis of the complete pre-S2/S (large S) genes
      (831 nt) demonstrated that all the viruses belonged to the same genotype E. So
      far, no isolates of genotype E have been found in any other region of the world,
      including the Americas. This may suggest a relatively recent introduction of this
      genotype into humans and would explain the relatively low genetic diversity of
      viruses belonging to this genotype. One genotype E virus had been found
      previously in a chimpanzee, and viruses belonging to the CHIMP genotype are
      related to other genotype E viruses. These findings are compatible with a
      transmission of genotype E viruses from chimpanzees to humans.

PMID- 11596080
TI  - Reactivation of precore variant hepatitis B virus in a child with severe aplastic
      anaemia.
AB  - Reactivation of hepatitis B e antigen (HBeAg) negative chronic hepatitis B virus
      (HBV) infection due to selection of precore variant virus is an uncommon
      complication of previous hepatitis B infection, and virtually unrecognised in
      children and adolescents. A child who had received treatment with
      methylprednisolone and antilymphocyte globulin for severe aplastic anaemia
      developed high levels of detectable HBV DNA associated with hepatitis B e
      antibody (anti-HBe) positivity. HBV DNA was extracted, amplified and the core and
      precore regions sequenced from 2 samples. A mixture of wild-type and the precore
      variants A(1896) and A(1899) was detected in both samples, with the wild-type
      predominating in the second sample. Reinfection was excluded by phylogenetic
      analysis using Phylip and the neighbour-joining method. Precore variant Hepatitis
      B virus can be transmitted to children as a primary infection, and it is
      important that aggressive liver disease, particularly in the presence of the anti
      HBe phenotype, be investigated. Further studies are needed to determine the
      frequency of these variants.

PMID- 11596081
TI  - Hepatitis B virus reactivation during cytotoxic chemotherapy-enhanced viral
      replication precedes overt hepatitis.
AB  - The diagnosis of HBV reactivation during cytotoxic chemotherapy is based on an
      abrupt rise in levels of serum HBV DNA in conjunction with a hepatitic picture
      and in the absence of other causes of hepatitis. However, several cases of
      "hepatitis" have been noted during chemotherapy in HBsAg-positive patients, for
      which no cause could be found and in which HBV DNA levels were negative. One
      possible explanation is that HBV reactivation may, indeed, have been the cause
      but that HBV DNA levels became negative by the time ALT levels peaked and the
      clinical diagnosis of hepatitis was made. During the course of a longitudinal
      study of HBsAg-seropositive cancer patients who were monitored during standard
      chemotherapy, the opportunity was available to test this hypothesis.

PMID- 11596082
TI  - Hepatitis B virus concentrations in serum determined by sensitive quantitative
      assays in patients with established chronic hepatitis delta virus infection.
AB  - To clarify the correlation between hepatitis B virus (HBV) DNA levels and serum
      alanine aminotransferase (ALT) levels in patients with established chronic
      hepatitis delta virus (HDV) infection, sensitive HBV quantitative assays were
      used for the study. Thirty-four consecutive patients with chronic liver disease
      who were positive for both hepatitis B surface antigen (HBsAg) and antibody to
      HDV (anti-HDV), including 19 patients with chronic hepatitis, 8 patients with
      liver cirrhosis and 7 patients with hepatocellular carcinoma. All were negative
      for hepatitis Be antigen (HBeAg) and positive for antibody to HBeAg. HBV DNA was
      detected in 25 (73.5%) of the 34 patients using real-time detection PCR, and the
      HBV DNA levels of these patients were significantly lower compared with HBeAg
      status and ALT level-matched patients with chronic liver disease positive for
      HBsAg but negative for anti-HDV. There was no correlation between serum HBV DNA
      and ALT levels among the 34 patients with chronic liver disease positive for anti
      HDV. Whereas serum ALT levels in anti-HDV-positive HBsAg carriers with HDV RNA
      were significantly higher than those without HDV RNA. Liver damage in patients
      with established chronic HDV infection may be caused mainly by ongoing HDV
      infection not by HBV replication.

PMID- 11596083
TI  - Molecular analysis of hepatitis B virus genomes isolated from black African
      patients with fulminant hepatitis B.
AB  - To investigate further the possible role of mutant hepatitis B viruses in the
      pathogenesis of fulminant hepatitis B, the genomic sequence of hepatitis B virus
      isolates from 9 South African blacks with this disease, including 5 entire
      genomes, was analysed. Seven of the isolates were genotype A. The mutation most
      often reported in patients with fulminant hepatitis B, the G1896A precore stop
      codon substitution, was, as expected, not present in the genotype A isolates with
      the exception of one in which it was accompanied by a compensatory C1858T
      substitution. G1896A was, however, present in the one genotype D isolate. No
      other precore-defective mutants were detected. The other mutation commonly found
      in patients with fulminant hepatitis B, the paired A1762T, G1764A substitution in
      the basic core promoter, was present in only one patient and G1764A in one other.
      The pre-surface initiation-codon mutation documented in a number of patients with
      fulminant hepatitis B was not found in our isolates. An 18-amino acid deletion
      present in the pre-surface region of one isolate has not previously been
      described in fulminant hepatitis B. Variations within the surface region were
      mainly genotype specific and not previously described. A relatively large number
      of mutations were present in the middle region of the core gene in those isolates
      without G1896A or A1762T, G1764A mutations, although the pattern was not
      consistent with those in published studies. Thus, as in other published series in
      which the entire genome of hepatitis B virus responsible for fulminant hepatitis
      was sequenced, we detected many mutations in different genes, but none was common
      to all the reported isolates.

PMID- 11596084
TI  - Residual hepatitis B virus particles in liver transplant recipients receiving
      lamivudine: PCR quantitation of HBV DNA and ELISA of preS1 antigen.
AB  - Lamivudine, an antiviral agent, has a potential role in the treatment of
      recurrent or acquired de novo hepatitis B virus (HBV) infection after liver
      transplantation. During lamivudine therapy, residual HBV particles in serum,
      PBMC, and liver were quantified in 7 patients in whom hepatitis B occurred de
      novo (n = 4) or recurred (n = 3). HBV DNA and preS1 antigen were measured using a
      sensitive PCR technique and an in-house ELISA method, respectively. The genetic
      and antigenic properties of HBV variants that emerged during lamivudine treatment
      were also examined. One month after the outset of lamivudine treatment, all 7
      patients remained positive for both HBV DNA and preS1 antigen in serum,
      reflecting residual HBV replication. At the end of therapy, four patients were
      considered to be lamivudine responders, including one who seroconverted to anti
      HBs but remained HBV DNA positive in the liver (> 10(3) copies/microg of DNA).
      Among the three patients who did not respond to lamivudine, one had pol mutations
      (L450P and S550C) that had not been described previously, in addition to the
      common mutations within the YMDD locus and B domain. Defective core and preS
      viral proteins and atypical sedimentation profiles of HBV DNA-positive particles
      were observed in all three lamivudine-resistant patients. These findings confirm
      the persistence of HBV in liver transplant recipients despite strong inhibition
      of replication by lamivudine, and show abnormal viral transcription and/or
      morphogenesis in lamivudine-resistant patients.

PMID- 11596085
TI  - Hepatitis C viral genotype influences the clinical outcome of patients with acute
      posttransfusion hepatitis C.
AB  - Most patients with an acute infection of hepatitis C virus (HCV) will develop
      chronic hepatitis, and only about 15-20% of the cases will resolve spontaneously.
      The mechanism for the different outcomes in patients with acute HCV infection
      remains unclear. HCV genotype has been recognized as an important factor
      affecting the clinical course and outcome of chronic hepatitis C patients. In
      order to evaluate the role of HCV genotype in the clinical course and outcome of
      acute posttransfusion hepatitis C, 67 patients with acute posttransfusion
      hepatitis C from a prospective study of posttransfusion non-A, non-B hepatitis
      were enrolled. Thirty-nine patients (58.2%) were HCV genotype 1b. Among the 67
      patients with acute posttransfusion hepatitis C, 53 (79.1%) progressed to chronic
      hepatitis. Significantly more patients with genotype 1b than non-1b genotypes
      developed chronic hepatitis (89.7% vs. 64.3%; P = 0.019). There was no
      significant difference in gender, mean age, amount of transfused blood, hepatitis
      symptoms, jaundice, incubation period, peak serum alanine transaminase, or serum
      HCV RNA titer between patients with HCV genotype 1b and non-1b infections.
      Patients who developed chronic hepatitis had a significantly greater incidence of
      genotype 1b infection (66.0% vs. 28.6%; P = 0.013) and a longer incubation period
      (7.3 weeks vs. 5.4 weeks; P = 0.052) than patients whose infection was resolved.
      Patients with a genotype 1b infection that resolved itself spontaneously all had
      an incubation period of less than 6 weeks. Multivariate logistic regression
      analysis revealed that genotype 1b and an incubation period > or = 6 weeks were
      significant predictive factors for the development of chronic hepatitis.
      Therefore, the HCV genotype can influence the outcome of patients with acute HCV
      infection.

PMID- 11596086
TI  - Ethnicity and cytokine production gauge response of patients with hepatitis C to
      interferon-alpha therapy.
AB  - Interferon is the primary treatment for hepatitis C virus (HCV). However, the
      long-term success rate is low particularly for African Americans relative to
      Caucasians and may be due to differential immune abilities. This study compared
      cytokine production from PHA-stimulated peripheral blood from 25 healthy and 40
      HCV-infected African Americans and Caucasians. HCV patients were designated as
      IFN responders or nonresponders based on outcome after therapy. Ethnicity and
      genotype were associated with IFN response. IFN responders were 100% Caucasian,
      whereas nonresponders were 67% Caucasian and 33% African American (P = 0.01).
      Genotype 1 was present in 100% nonresponders and 50% responders (P < 0.05). Age,
      sex, liver histology, ALT, and viral titers were equivalent (ns). Cytokine
      production from healthy individuals showed ethnic variation in cytokine levels.
      Healthy African Americans produced greater amounts of IL-2 (P = 0.06), TNF-alpha
      (P = 0.06) and less IL-10 (P = 0.05) than healthy Caucasians. In contrast, IFN
      gamma and TGF-beta levels were equivalent. Pretherapy cytokine production among
      HCV patients showed a similar pattern of ethnic variation. African American
      nonresponders produced more IL-2 (P = 0.06) and TNF-alpha (P = 0.02) than
      Caucasian nonresponders. Cytokine levels among Caucasian and African American
      nonresponders were equivalent (P = ns) to ethnically matched healthy individuals
      whereas Caucasian responders produced subnormal levels of IL-10 (P < 0.05) and
      TGF-beta (P < 0.05). Since all African Americans failed IFN therapy, cytokine
      production could not be compared with therapeutic outcome. However, comparison of
      cytokine production among Caucasians showed that responders produced less IL-10
      (P < 0.001) and more TGF-beta (P = 0.06) than nonresponders and predicted
      Caucasian nonresponders with 83% sensitivity and 96% specificity. HCV genotype
      was not relevant to cytokine production (P = ns). Distribution of cytokine
      genetic polymorphisms (TNF-alpha, TNF-beta, IL-10, TGF-beta) was equivalent in
      all ethnic groups and did not predict clinical nonresponders. In summary, it
      appears that ethnicity may contribute to variable immune responses and
      therapeutic outcome. The cytokine profile among African Americans suggests a more
      robust immune response, which may complicate therapy with IFN. In contrast, the
      subnormal cytokine production among Caucasian responders may be more permissive
      to IFN therapy. Pretherapy cytokine production may allow prediction of drug
      resistance among Caucasians.

PMID- 11596087
TI  - Shift in predominating subtype of HCV from 1b to 3a in St. Petersburg mediated by
      increase in injecting drug use.
AB  - The genotypes of 149 HCV strains from St. Petersburg were determined by limited
      sequencing and phylogenetic analysis within the NS5B region. One hundred two
      strains derived from patients that attended infectious disease clinics, of whom
      48 admitted injecting drug use, and 47 derived from dialysis patients. Subtype 3a
      was predominant in the patients from infectious disease clinics, both in patients
      that admitted injecting drug use (56%) and in those with unknown source of
      infection (46%). However, 89% of the strains from dialysis patients belonged to
      subtype 1b. Eleven of twelve characterised strains from recent cases of hepatitis
      C at these units were at phylogenetic analysis shown to be related to strains
      already circulating there, demonstrating that within the dialysis units
      nosocomial transmission is the most important route of HCV infection. The
      predominance of subtype 1b strains in dialysis patients indicates that these
      strains have been circulating for a long time in dialysis units. The predominance
      of subtype 3a also among patients who did not admit drug use and that their
      strains were intermixed with the strains from injecting drug users in the
      phylogenetic analysis shows that the increase in injecting drug use is the major
      factor that explains the recent spread of HCV in the St. Petersburg population.
      This supports the concept that injecting drug use remains the major route for HCV
      infection in developed countries and that the control of drug abuse is the most
      important measure to prevent its spread.

PMID- 11596088
TI  - Detection and characterisation of swine hepatitis E virus in New Zealand.
AB  - The objectives of the present study were to establish the presence of hepatitis E
      virus (HEV) in New Zealand pigs, first by testing for HEV antibody in pig herds
      throughout New Zealand to measure the herd prevalence, then by attempting to
      amplify HEV genomic sequences by PCR. Antibody was measured by two independently
      designed ELISA serology tests. HEV RNA fragments were amplified by RT-PCR of
      nucleic acid extracted from faeces of 10-12-week-old piglets using primers
      targeting ORF1, ORF2, and ORF2/3. PCR products were subject to phylogenetic
      analysis. Antibody to HEV was found throughout New Zealand pig herds as well as
      in the different age groups within the herds. Twenty herds from 22 tested were
      positive for HEV antibody (91% herd prevalence). Phylogenetic analysis of the
      amplified sequences placed this New Zealand strain of HEV closest to the human
      European strain It-1 (AF 110390) and U.S. swine strain (AF 082843) with 88% and
      83% similarity respectively in ORF1. It was concluded that HEV is widely
      distributed in the New Zealand pig population. Phylogenetic analysis shows that
      this is a new HEV strain, grouping most closely with the United States/European
      cluster, which includes HEV strains of both human and swine origin.

PMID- 11596089
TI  - New genome type of adenovirus serotype 19 causing nosocomial infections of
      epidemic keratoconjunctivitis in Japan.
AB  - Twelve strains of adenovirus serotype 19, isolated from cases of epidemic
      keratoconjunctivitis in Japan in 1992, 1993, 1997, and 1998, were analyzed by DNA
      restriction analysis, using restriction endonucleases BamHI, BglI, BglII, EcoRI,
      HindIII, KpnI, PstI, SacI, SalI, SmaI, and XhoI. Among these 11 restriction
      endonucleases, EcoRI, PstI, SacI, and SmaI were discriminative enzymes, showing
      restriction patterns different from those reported previously for the prototype
      and the variant 19a. This new genome type was isolated in 1997 and 1998, when an
      increase of epidemic keratoconjunctivitis cases caused by adenovirus serotype 19
      was observed for both sporadic and nosocomial infections. Strains from 1992 and
      1993 showed restriction patterns similar to those of the worldwide reported
      variant 19a for all enzymes used. The changes detected in strains from 1997 and
      1998 could be the reason for the recent epidemic.

PMID- 11596090
TI  - A-549 is a suitable cell line for primary isolation of coxsackie B viruses.
AB  - A common receptor for coxsackie B virus and adenovirus has been described
      recently in cells of human and murine origin. Since the established cell line A
      549 is suitable for adenoviruses, the potential use of A-549 cells for the
      isolation of coxsackie B viruses from clinical samples was investigated. All
      throat swabs sent to the laboratory between April 1998 and June 1999 were
      inoculated onto monolayers of MRC-5 and A-549 cells in tubes, and the enterovirus
      isolates obtained were typed. From April to June 1999, A-549 cells were compared
      prospectively to Buffalo green monkey (BGM) cells, considered as the most
      susceptible cell line for isolating coxsackie B viruses. Fifty-six out of 171
      enterovirus isolates (33%) displayed a cytopathic effect (CPE) in the A-549
      monolayer only, 48 isolates (28%) in the MRC-5 monolayer only, and 67 isolates
      (39%) in both cell lines. Most isolates that showed CPE in A-549 cells only (48
      out of 56, 86%) were coxsackie B viruses, belonging to four different serotypes
      (B1, B2, B4, and B6). When BGM and A-549 cells were inoculated in parallel, both
      recovered the same number of coxsackie B isolates (n = 20), and the CPE was noted
      on approximately the same day. In conclusion, growth in A-549 but not MRC-5 cells
      identified coxsackie B viruses in most cases. A-549 was comparable to BGM for
      primary isolation of coxsackie B viruses.

PMID- 11596091
TI  - Human cytomegalovirus gB genotype 1 is dominant in congenital infections in South
      Hungary.
AB  - On the basis of the sequence variation of the glycoprotein B (gB) gene, human
      cytomegalovirus (HCMV) can be classified into four gB genotypes. Genotyping of
      HCMV from congenital infections was carried out on the assumption that the
      envelope gB may influence the outcome of prenatal infection. Sixty-three pregnant
      women were included in the study: 40 pregnant women whose fetuses were strongly
      suspected of having viral infection, and 23 women with normal pregnancies, from
      whom amniotic fluid was taken for fetal karyotype assessment. The amniotic fluid,
      fetal blood, blood, and urine of the newborns were examined for HCMV DNA by a
      nested polymerase chain reaction, and the gB genotype was determined by
      restriction fragment length polymorphism. HCMV DNA was detected in 12 cases in
      which the fetuses were suspected of having a viral infection and in 3 of the
      normal pregnancies. All the HCMV DNA had identical genotype, gB1. These data
      clearly indicate the dominance of the gB1 genotype in congenital HCMV infections.
      The clinical outcome of these pregnancies, however, cannot be predicted on the
      basis of the involvement of this genotype.

PMID- 11596092
TI  - Quantification of Epstein-Barr virus load in peripheral blood of human
      immunodeficiency virus-infected patients using real-time PCR.
AB  - Epstein-Barr virus (EBV) reactivation is more likely to occur in
      immunocompromised patients with subsequent higher susceptibility to EBV
      associated lymphoproliferations. In contrast to transplant recipients, limited
      data are available concerning the EBV load in HIV-infected patients, with or
      without AIDS-related non-Hodgkin's lymphomas. We developed a TaqMan real-time PCR
      assay, allowing both the EBV genome and a cellular gene to be quantified in order
      to obtain a reliable normalized measurement of the EBV load in peripheral blood
      mononuclear cells (PBMCs). With a wide 6-log(10) quantification range and inter
      assay variations of less than 24%, this quantitative PCR was sufficiently
      accurate and reproducible for routine follow-up. The EBV load was determined in
      PBMCs from 113 HIV-infected patients, 11 patients with primary HIV infection and
      24 HIV-seronegative healthy controls. The rates of EBV detection were similar in
      the three groups. However, EBV loads were higher in the HIV-infected group (P <
      0.00001) except for the patients with primary HIV infection. Unexpectedly, EBV
      loads were not correlated with the clinical stages of HIV infection or HIV
      replication, and did not depend on the degree of immunodepression, as judged by
      CD4+ counts. This study contributes towards the definition of the baseline EBV
      load during HIV infection and stresses the broad inter-individual variability of
      the EBV load in HIV-infected patients. Real-time PCR provides a useful tool that
      can be used in further longitudinal studies to assess the relevance of the EBV
      load to identify HIV-infected patients with a high risk of EBV-associated
      lymphoproliferations.

PMID- 11596093
TI  - High-level expression of recombinant dengue viral NS-1 protein and its potential
      use as a diagnostic antigen.
AB  - The prevalence of NS1 Ab response in patients with dengue viral infection and the
      potential of using recombinant NS1 protein as a diagnostic antigen for dengue
      viral infection were investigated. In this study, the full-length and C-terminal
      half of NS1 proteins (rNS1, rNS1-C) were highly expressed (10-30 mg/l) and
      further purified and refolded. The good antigenicity of the full-length rNS1
      protein was confirmed by interaction with 19 dengue NS1-specific monoclonal
      antibodies (MAbs) in ELISA; however, the antigenicity of rNS1-C was relatively
      lower. The full-length rNS1 antigen also differentiated reliably between sera
      from dengue virus-infected patients and sera from normal controls. When rNS1 was
      used as an antigen to detect human anti-NS1 IgM and IgG Ab, the anti-NS1 Ab
      response was found in 15 of 17 patients (88%) with primary dengue infection and
      all 16 patients (100%) with secondary dengue infection. These results indicated
      that using the full-length rNS1 whose antigenicity is restored as ELISA antigen,
      a high anti-NS1 antibody prevalence could be detected in patients with either
      primary or secondary dengue infection. This finding suggested that the anti-NS1
      antibody appeared not only in secondary and severe dengue virus infection and
      might not correlate the pathogenesis of dengue hemorrhagic fever. The study also
      verified that our purified rNS1 protein showed similar immunological properties
      as native dengue viral proteins. Genetic engineering production of recombinant
      NS1 antigen could provide a safe and valuable resource for dengue virus
      serodiagnosis.

PMID- 11596094
TI  - Multiplex analysis of cytokines in the blood of cynomolgus macaques naturally
      infected with Ebola virus (Reston serotype).
AB  - Ebola virus (EBO) causes the most severe form of viral hemorrhagic fever in
      humans and nonhuman primates with up to 90% of infections culminating in death.
      The requirement of maximum containment laboratories for Ebola virus research has
      limited opportunities to study the pathogenesis of EBO infections. While tissue
      damage does occur, often it would appear not to be sufficient to explain death,
      indicating that soluble mediators play an important role in disease progression.
      In previous studies, fatal human infections with the Zaire subtype of Ebola (EBO
      Z) were associated with an increase in the levels of inflammatory cytokines. In
      this investigation, a new multiplex assay was developed and used to measure
      circulating levels of cytokines and chemokines in cynomolgus macaques infected
      with the Reston subtype of EBO (EBO-R). Increased levels of IL-6, TNF-alpha, IFN
      gamma, IL-2, IL-4, IL-8, IL-10, and GM-CSF were detected in infected animals, and
      the increase in circulating cytokines correlated with an increase in circulating
      viral antigen. Blood samples from animals showing high levels of cytokines were
      also tested for the chemokines: MCP-1, IL-1beta, MIP-1alpha, MIP-1beta, IP-10,
      and RANTES. High levels of MCP-1 and MIP-1beta, and RANTES were found in infected
      primates and, while levels were more variable, IL-1beta was detected only in
      infected animals.

PMID- 11596095
TI  - Molecular cloning and expression of woodchuck granulocyte-macrophage colony
      stimulating factor.
AB  - Granulocyte-macrophage colony stimulating factor (GM-CSF) has immunoregulatory
      and antiviral effects, and may thus be promising for the treatment of chronic
      hepatitis B. Using woodchuck hepatitis virus (WHV)-infected woodchuck as an
      animal model to test the efficacy and safety of GM-CSF on the therapy of chronic
      hepatitis B, woodchuck GM-CSF will be required due to the apparent species
      specific activity of GM-CSF. The cDNA of woodchuck GM-CSF was cloned using
      reverse transcription-polymerase chain reaction (RT-PCR) with primers deriving
      from highly conserved regions of GM-CSF genes from other species. The deduced
      amino acids, including the signal peptide, is 138 in length and its identities to
      human, murine, canine and bovine GM-CSFs are 63, 49, 63, and 63% respectively.
      The genomic DNA of woodchuck GM-CSF was also cloned by PCR. Its organization is
      highly homologous to that of human and murine GM-CSF genes, consisting of four
      exons and three introns. Cloned woodchuck GM-CSF was expressed transiently in
      293T cells. The recombinant protein expressed was found to stimulate the growth
      and differentiation of woodchuck bone marrow cells, indicating the protein
      expressed by the cloned gene is functional. These results pave the way for future
      studies on the potential role of GM-CSF for the treatment of chronic hepatitis B
      by using this animal model.

PMID- 11596096
TI  - Human herpesvirus 6 downregulates major histocompatibility complex class I in
      dendritic cells.
AB  - The expression of major histocompatibility complex (MHC) class I, class II, CD1a,
      and CD 83 in dendritic cells (DCs) after infection with human herpesvirus 6 (HHV
      6) was examined. Whereas there was no significant change in the expression of
      CD1a, CD83, and MHC class II in infected DCs, MHC class I expression was
      downregulated after infection with HHV-6 variant A but not HHV-6B. The expression
      of HHV-6 immediate-early or early genes was required for the downregulation of
      MHC class I. The de novo synthesis of MHC class I was greatly suppressed by
      infection with HHV-6A in DCs, while its rate of degradation was only slightly
      elevated. These results suggest that HHV-6A may escape from the host immune
      system in DCs by causing the downregulation of MHC class I synthesis.

PMID- 11596097
TI  - Vaccination-induced HI antibody response to intraepidemic influenza A(H3N2) virus
      variants of the 1996-1997 epidemic season.
AB  - Intraepidemic antigenic and genetic variation was indicated when H3N2-subtype
      influenza A virus strains isolated during the 1996-1997 epidemic season in
      Finland were studied for reactivity in the haemagglutination inhibition (HI)
      assay and for nucleotide sequences coding for the variable HA1 domain of viral
      haemagglutinin. Thirty prevaccination- and postvaccination-paired sera taken from
      subjects who had been vaccinated against influenza during the previous autumn
      were studied for the presence of HI antibody to the homologous vaccine virus
      A/Nanchang/933/95, and five field strains representing the genetic and antigenic
      variability of the 1996-1997 epidemic season. The lowest vaccination-induced HI
      titres in each of the three age groups were detected in the two field strains
      that had been isolated from vaccinated patients and belonged to two different
      genetic sublineages. The intraepidemic variability of the 1996-1997 field strains
      in HI reactivity may be indicative of circulation of virus strains that may be
      capable of breaking through vaccination-induced immunity better than the other
      strains.

PMID- 11596098
TI  - Genetic analysis of an influenza B virus isolated from a patient with
      encephalopathy in Japan.
AB  - An influenza B virus, B/Saga/S172/99 (SAG99), was isolated from the nasopharynx
      of a patient with encephalopathy/encephalitis in Japan in 1999. To clarify the
      molecular characteristics of this virus, detailed analysis of the gene segments
      coding for the hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix
      protein (M) and non-structural protein (NS) was undertaken. All five genes of
      SAG99 showed high nucleotide and predicted amino acid similarities with those of
      recent non-encephalopathic strains isolated in the same epidemic season.
      Subsequent phylogenetic analysis revealed that all five gene segments of SAG99
      analyzed in the present study were most similar to those of the recent
      Yamagata/16/88-like viruses. The hemagglutinin and neuraminidase proteins of
      SAG99 were each distinguished from those of recent epidemic strains by one
      characteristic amino acid substitution. These substitutions were not found in the
      previously reported encephalopathy/encephalitis-derived influenza B viruses, and
      we could not find any common characteristic amino acid changes in SAG99 and these
      viruses. Similarly, among the internal proteins studied, only the M2 protein of
      SAG99 was found to contain a single novel amino acid change when compared with
      other recent isolates. Thus, it was apparent that SAG99 contained very few amino
      acid differences when compared with other epidemic viruses. The association of
      recent B/Yamagata/16/88-like viruses with encephalitis/encephalopathy observed in
      the present study and previously suggest that these viruses may have a higher
      potential for causing neurological complications in certain individuals.

PMID- 11596099
TI  - Epidemic of jungle yellow fever in Brazil, 2000: implications of climatic
      alterations in disease spread.
AB  - Seventy-seven human cases of sylvatic yellow fever were reported in Brazil during
      the period January-June 2000. The first cases were reported 1 week after New
      Year's day and originated at Chapada dos Veadeiros, a tourist canyon site in
      Goias state, near Brasilia, the Brazilian capital. The laboratory procedures used
      for diagnoses included serology with an IgM capture assay and plaque reduction
      neutralization test, virus isolation in suckling mice and C6/36 cells, and
      immunohistochemistry. All cases were diagnosed by at least two different
      laboratory procedures, with the exception of the first three fatal cases, which
      were diagnosed on the basis of clinical and epidemiological information. The
      cases were reported in eight Brazilian states as follows: Goias with 64.9% (50
      cases); Amazonas (1); Bahia (10); Distrito Federal (1); Mato Grosso (4); Minas
      Gerais (2); Para (1); Sao Paulo (2); and Tocantins (6). Patient ages were within
      the following ranges: 13-74 years old (mean 34.3), 64 (84.4%) were male,
      especially agricultural workers (n = 30), but tourists (n = 11), carpenters (n =
      4), fishermen (n = 4), students (n = 3), truck drivers (n = 3), and other people
      (n = 22) were also sickened. The case fatality rate was 50.6% (39/77). In Bahia
      state, a serologic survey that was carried out has suggested a
      symptomatic/asymptomatic coefficient of 1:4. Field studies developed in Distrito
      Federal, Goias, and Sao Paulo states showed that Haemagogus janthinomys was the
      mosquito species associated with the transmission. A single strain was also
      obtained from Aedes scapularis in Bahia. Epizootic occurrence (monkey mortality)
      was observed in 49 municipalities mainly in Goias state, where 40 municipalities
      made reports, 21 of which also diagnosed human cases. Data obtained by the
      National Institute of Meteorology in Brazil showed an increase in temperature and
      rain in December 1999 and the first 3 months of 2000 in Goias and surrounding
      states, which perhaps has contributed to the intense and widespread transmission
      of the yellow fever virus. The relatively small number of cases probably reflects
      the extensive use of yellow fever 17D-vaccine during the last 3 years, in which
      about 45 million doses were used. During the last months of 1999, 16 and 11
      yellow fever cases were reported in Tocantins and Goias states, respectively. It
      is noteworthy that the last reported autochthonous cases of sylvatic yellow fever
      in Sao Paulo and Bahia, both states outside the endemic/enzootic area, had
      occurred in 1953 and 1948, respectively.

PMID- 11596100
TI  - Human immune response to Puumala virus glycoproteins and nucleocapsid protein
      expressed in mammalian cells.
AB  - Puumala hantavirus (PUUV) glycoproteins G1 and G2 and nucleocapsid protein (N)
      were expressed in BHK-21 cells by transfection of a plasmid producing a
      recombinant alphavirus replicon. Coexpression of G1 and G2 from separate
      constructs seemed to be important for the optimal folding of the glycoproteins,
      as evaluated by a panel of MAbs detecting conformational epitopes. To evaluate
      the human antibody response against recombinant G1, G2 and N, several panels of
      sera were tested by immunofluorescence assay (IFA). Also human sera showed the
      best reactivity towards G1 and G2 coexpressed from separate transcripts (G1 +
      G2). Notably, only 2% of the acute sera (total number = 133) contained IgG
      antibodies against G1 + G2, whereas of old-immunity sera (total number = 100) 87%
      were G1 + G2 positive. Analysis of a panel of serial patient sera showed that as
      the immunity matured, IgG antibodies against the recombinant glycoproteins
      appeared and the titers increased in the course of time, while antibodies against
      the recombinant N were present already in the acute phase in high titers. The
      granular fluorescence pattern in PUUV IgG-IFA, associated with the acute phase of
      immunity, was linked to the presence of antibodies against N, whereas the diffuse
      fluorescence pattern associated with old-immunity, was linked to the development
      of antibodies against G1 + G2. The granular fluorescence pattern in PUUV IgG-IFA
      had a predictive value of 100% for acute PUUV infection. Weak cross-reaction with
      PUUV glycoproteins was observed in 36% of old-immunity DOBV-specific human sera.

PMID- 11596101
TI  - Quantitative study of the infection in brain neurons in human rabies.
AB  - Rabies virus is a highly neuronotropic virus that causes encephalomyelitis.
      Rabies virus infection was studied in neurons in the brain of an 8-year-old girl
      that died of rabies in Mexico. The extent of the neuronal infection was evaluated
      quantitatively in neuronal cell types of the brain using histologic staining for
      Negri bodies and immunoperoxidase staining for rabies virus antigen in the same
      neurons. Quantitative image analysis was used to compare the amount of infection
      in five different neuronal cell types, which was expressed as a percentage of
      neuronal area. Purkinje cells and periaqueductal gray neurons showed the largest
      percentage area for both Negri bodies and signal for rabies virus antigen. In
      general, there was a good linear relationship between the area of Negri bodies
      and the area of signal for rabies virus antigen. Many neurons with rabies virus
      antigen did not have Negri bodies, however, and some neurons with large antigen
      signals, especially Purkinje cells and periaqueductal gray neurons, lacked Negri
      bodies. Formation of Negri bodies is likely influenced by factors that vary in
      different neuronal cell types.

PMID- 11596102
TI  - Characterization of human rotavirus serotype G9 isolated in Japan and Thailand
      from 1995 to 1997.
AB  - Serotyping of human rotavirus was conducted in 396 Japanese and 100 Thai
      rotavirus-positive fecal specimens collected from 1995 to 1997. Serotype G9 was
      found to be the third most common serotype with frequency of 16.2% in Thailand
      from 1996 to 1997. It was also detected in Japan with a low frequency (0.7%) in
      this year. The genetic analyses of VP4 and NSP4 genes of these G9 strains showed
      that 1 strain from Japan possessed P[8] genotype and NSP4 Wa-group with long
      electropherotype (e-type). In contrast, 5 strains from Thailand belonged to P[6]
      and 1 strain belonged to P[4]. All of the Thai strains were in the NSP4 KUN-group
      with a short e-type. Sequence analysis of their VP7 gene revealed that there was
      the highest homology among fecal G9 strains (> 96.3%, amino acid identity) and a
      relatively high degree of homology to standard viruses, F45 from Japan (95.4
      96.3%, amino acid identity) and 116E from India (92-92.3%, amino acid identity).
      However, immunological analysis using G9 specific monoclonal antibodies (Mabs)
      against VP7 protein showed that the G9 strains isolated from the two countries
      had different antigenic specificity. It was confirmed further by intraserotypical
      phylogenetic analysis of VP7 amino acid. These results indicated that the
      prevalence of G9 rotavirus in 1996-1997 in Thailand was relative to the
      continuing recent emergence of it on a worldwide basis, while the Japanese G9
      strain isolated in this survey was identified to have progenitors common to the
      F45 strain that was prevalent in 1985 in Japan. Phylogenetic analysis of VP7
      amino acid of G1-14 prototype rotavirus showed that the G9 strains were most
      closely related to the equine G14 rotavirus FI23 strain but G3 strains,
      interserotypically. These findings suggest that G9 rotaviruses might be divided
      into two or more subtypes.

PMID- 11596104
TI  - Single-stranded nucleic acid-binding protein, Pur alpha, interacts with RNA
      homologous to 18S ribosomal RNA and inhibits translation in vitro.
AB  - Pur alpha is a highly conserved, eukaryotic sequence-specific DNA- and RNA
      binding protein involved in diverse cellular and viral functions including
      transcription, replication, and cell growth. Pur alpha exerts its activity in
      part by interacting with other viral and cellular proteins. One such protein is
      the human immunodeficiency virus (HIV) type I regulatory protein Tat. Earlier
      studies have demonstrated that this interaction is mediated by Pur alpha
      associated RNA (PARNA) and that RNA immunopurified from mammalian expressed Pur
      alpha was capable of reconstituting the interaction between these two proteins.
      In the current study, we characterize four RNA species which were immunopurified
      with Pur alpha. Northern blot analysis with one of the PARNAs revealed a highly
      abundant signal of approximately 2.0 kilobases (kb) present in all cell lines
      tested. Sequence analysis of each of the four PARNA clones revealed a high
      homology to different regions of the human 18S ribosomal RNA sequence. Based on
      this homology, we investigated the influence of Pur alpha on translation.
      Luciferase assays were performed after coupled in vitro transcription/translation
      reactions with a vector containing a luciferase reporter construct and increasing
      concentrations of BSA, GST, and GST-Pur alpha. Inclusion of GST-Pur alpha in
      these reactions resulted in a dose-dependent inhibition of luciferase activity.
      Similar inhibition was observed with in vitro translation reactions performed
      with in vitro transcribed luciferase RNA and increasing concentrations of GST-Pur
      alpha. In control experiments, inclusion of increasing concentrations of GST-Pur
      alpha with luciferase protein resulted in no effect on luciferase activity. Taken
      together, these data demonstrate that Pur alpha inhibits translation reactions in
      vitro. Moreover, this Pur alpha-mediated inhibition of translation can be
      abrogated by HIV-1 Tat protein.

PMID- 11596105
TI  - Expression of AP-2 transcription factor and of its downstream target genes c-kit,
      E-cadherin and p21 in human cutaneous melanoma.
AB  - The AP-2 transcription factor plays a pivotal role in regulating the expression
      of several genes involved in tumor growth and progression of melanoma. We
      determined, by Western blot, variation in the level of expression of AP-2 and
      three of its downstream targets, c-kit, E-cadherin, and p21 in several human
      melanoma cell lines and, by immunohistochemistry, in a group of 99 histological
      samples including benign and malignant melanocytic lesions. A significant
      negative correlation between AP-2 expression level and tumor thickness was found.
      Moreover, AP-2 expression was positively associated with E-cadherin and c-kit
      expression. In contrast, there was a significant negative association between AP
      2 and p21 expression levels. These findings suggest that p21 is independent of AP
      2 transactivator function during the latest phases of melanoma progression.
      Finally, AP-2, c-kit, E-cadherin, and p21 expression levels did not show to be
      able to distinguish between dysplastic nevi and nevi without dysplasia. We
      conclude that changes in the expression of these proteins are involved in the
      later phases of melanoma progression, and may be responsible for the transition
      from local invasive melanoma to metastasis.

PMID- 11596106
TI  - Mammalian DNA methyltransferases show different subnuclear distributions.
AB  - In mammalian cells, DNA methylation patterns are precisely maintained after DNA
      replication with defined changes occurring during development. The major DNA
      methyltransferase (Dnmt1) is associated with nuclear replication sites during S
      phase, which is consistent with a role in maintenance methylation. The
      subcellular distribution of the recently discovered de novo DNA
      methyltransferases, Dnmt3a and Dnmt3b, was investigated by immunofluorescence and
      by epitope tagging. We now show that both Dnmt3a and Dnmt3b are distributed
      throughout the nucleoplasm but are not associated with nuclear DNA replication
      sites during S-phase. These results suggest that de novo methylation by Dnmt3a
      and Dnmt3b occurs independently of the replication process and might involve an
      alternative mechanism for accessing the target DNA. The different subcellular
      distribution of mammalian DNA methyltransferases might thus contribute to the
      regulation of DNA methylation.

PMID- 11596107
TI  - Dynamic changes in p27kip1 variant expression in activated lymphocytes.
AB  - The p27Kip1 cell cycle inhibitor (p27) has emerged as a critical mediator of
      normal cellular growth control. We report the expression of a 24 kD C-terminal
      variant of p27 in normal peripheral blood lymphocytes. This variant is rapidly
      degraded in a proteasome-dependent manner when lymphocytes are activated by
      interleukin-2 or by superantigen. Whereas p24 degradation is complete within 16 h
      of mitogen addition, full-length p27 is decreased only modestly over 72 h of
      mitogen exposure and is present in activated and cycling lymphocytes. Persistent
      p27 is present in a complex with cyclin D3 in activated lymphocytes, and is
      localized both in the nucleus and cytoplasm. These results indicate that
      lymphocytes exiting from quiescence use several mechanisms to overcome the
      p27Kip1-enforced cell cycle checkpoint, and that elimination of p27 is not
      required for cell cycle entry.

PMID- 11596108
TI  - Phorbol diester 12-O-tetradecanoylphorbol 13-acetate (TPA) up-regulates the
      expression of estrogen receptors in human THP-1 leukemia cells.
AB  - In the present work, we have inspected expression of estrogen receptors (ER) and
      their regulation by the phorbol diester 12-O-tetradecanoylphorbol 13-acetate
      (TPA) in a leukemic cell line, the THP-1 cells, using multiple experimental
      approaches. Firstly, ligand binding assay (LBA) revealed that control
      (unstimulated) THP-1 cells express type I (high affinity, limited capacity) ER in
      the nuclear fraction only, whilst treatment of cells with TPA resulted in the
      appearance of type I ER in the soluble fraction as well, with the 50 ng/ml dose
      and the 48 h incubation time being the most effective experimental condition. A
      concomitant increase of type II ER was also seen in both soluble and nuclear cell
      fractions. Unstimulated THP-1 cells were found to be ER negative by
      immunocytochemistry; conversely, cells exposed to 50 ng/ml TPA for 48 h stained
      positively for ER, with the majority of cells having a strong nuclear staining.
      Scrutiny of ER mRNA expression using reverse transcriptase-polymerase chain
      reaction showed the presence of a wild type ER transcript in both control and TPA
      treated THP-1 cells, though levels of ER mRNA were found to be comparatively
      higher in the latter. This combined evidence would imply that the TPA-induced
      differentiation of THP-1 cells is accompanied by the rise of high affinity (type
      I) ER, suggesting that estrogens may play a role in the regulation of macrophage
      activity during the inflammatory and/or the immune response.

PMID- 11596109
TI  - High dose of dexamethasone upregulates TCR/CD3-induced calcium response
      independent of TCR zeta chain expression in human T lymphocytes.
AB  - Glucocorticoids are very potent anti-inflammatory and immunosuppressive agents
      that modulate cellular immune responses, although, the molecular mechanisms that
      impart their complex effects have not been completely defined. We have previously
      demonstrated that dexamethasone (Dex), a synthetic glucocorticoid, biphasically
      modulates the expression of TCR (T cell receptor) zeta chain in human T cells. At
      10 nM, it induced the expression of TCR zeta chain whereas at 100 nM, it
      inhibited its expression. In parallel to the upregulation of TCR zeta chain, the
      TCR/CD3-mediated [Ca(2+)](i) response was enhanced in 10 nM Dex-treated cells.
      However, at 100 nM, Dex treatment enhanced TCR/CD3-mediated [Ca(2+)](i) response
      without the induction of TCR zeta chain expression. Because the classical
      transcriptional model of glucocorticoid action cannot account for the effects of
      high dose of Dex, here we studied alternative mechanisms of action. We show that,
      increased and more sustained TCR/CD3-mediated [Ca(2+)](i) response was also
      observed in 100 nM Dex-treated cells in the presence of actinomycin D or
      cycloheximide suggesting that cellular transcription and/or de novo protein
      synthesis are not required for the induction. The TCR/CD3-mediated hyper
      [Ca(2+)](i) response in 100 nM Dex-treated cells was readily reversible by short
      term culture in steroid-free medium. RU-486, a competitive antagonist of Dex,
      inhibited the increase in [Ca(2+)](i) response suggesting that the effect of Dex
      is mediated through the glucocorticoid receptor. Although the lipid-raft
      association of the TCR zeta chain was not significantly increased, high-dose of
      Dex increased the amount of ubiquitinated form of the TCR zeta chain in the cell
      membrane along with increased levels of actin. Fluorescence microscopy showed
      that high-dose of Dex alters the distribution of the TCR zeta chain and form more
      distinct clusters upon TCR/CD3 stimulation. These results suggest that high dose
      of Dex perturbs the membrane distribution of TCR zeta chain leading to more
      functional signaling clusters that result in increased TCR/CD3-mediated
      [Ca(2+)](i) response independent of TCR zeta chain expression.

PMID- 11596111
TI  - Effects of the circadian mutation 'tau' on the Harderian glands of Syrian
      hamsters.
AB  - The Syrian hamster Harderian gland (HG) is an organ continually exposed to
      oxidative stress caused by high concentrations of porphyric metabolites.
      According to previous studies, melatonin, which is rhythmically secreted by the
      pineal gland and tonically produced by the HG, antagonizes the oxidative damage.
      HGs exhibit a strong gender-dependent correlation between porphyrins, melatonin,
      and histological appearance. In HGs of both sexes, we have investigated effects
      of a single gene defect in the circadian clock system (tau mutation) causing a
      shortened free-running period and an advanced maximum of circulating melatonin.
      Comparisons were made with wild-type animals, one group of which received daily
      pharmacological injections of melatonin in late photophase. Changes were observed
      in histological characteristics, porphyrin content, antioxidant enzyme
      activities, and damage of proteins and lipids. HGs of tau hamsters showed
      morphological changes which can be partially interpreted in terms of increased
      damage. Additionally, tau females exhibited a many-fold augmentation in the
      percentage of so-called type II cells, which are otherwise typical for the male
      glands. In tau hamsters of both sexes, major antioxidative enzyme activities
      (superoxide dismutase, glutathione reductase, and catalase) were markedly
      enhanced, a presumably compensatory response to increased oxidative stress.
      Higher oxidative damage in tau HGs was directly demonstrable by a many-fold
      increase in protein carbonyl. Rises in antioxidative enzymes were also observed
      upon injections of melatonin; this was, however, not accompanied by changes in
      protein carbonyl, so that enzyme inductions by the hormone should be understood
      as protective actions. Our data are not only in accordance with findings on
      protective effects by melatonin, but also with our earlier observation made in
      Drosophila that perturbations in the circadian system lead to increased oxidative
      stress.

PMID- 11596110
TI  - Retinoblastoma protein complexes with C/EBP proteins and activates C/EBP-mediated
      transcription.
AB  - The retinoblastoma protein (RB) recruits histone deacetylase (HDAC) to repress
      E2F-mediated transactivation that plays a critical role in cell cycle regulation.
      RB is also involved in activation of expression of a number of tissue specific-
      and differentiation-related genes. In this study, we examined the mechanism by
      which RB stimulated the expression of a differentiation-related gene, the
      surfactant protein D (SP-D), which plays important roles in innate host defense
      and the regulation of surfactant homeostasis. We demonstrated that RB
      specifically stimulated the activity of human SP-D gene promoter. The RB family
      member, p107 but not p130, also increased SP-D promoter activity. Activation by
      RB was mediated through a NF-IL6 (C/EBP beta) binding motif in the human SP-D
      promoter, and this sequence specifically bound to C/EBP alpha, C/EBP beta, and
      C/EBP delta. RB formed stable complexes with all three C/EBP family members. RB
      small pocket (amino acid residues 379-792), but not the C-pocket (amino acid
      residues 792-928), was necessary and sufficient for its interaction with C/EBP
      proteins. Furthermore, we demonstrated that the complexes containing RB and C/EBP
      proteins directly interacted with C-EBP binding site on DNA. These findings
      indicate that RB plays a positive, selective, and direct role in the C/EBP
      dependent transcriptional regulation of human SP-D expression.

PMID- 11596112
TI  - Role of hydroxyl containing residues in the intracellular region of rat
      bradykinin B(2) receptor in signal transduction, receptor internalization, and
      resensitization.
AB  - In past reports we illustrated the importance of Y131, Y322, and T137 within the
      intracellular (IC) face of the rat bradykinin B2 receptor (rBKB2R) for signal
      transduction and receptor maintenance (Prado et al. [1997] J. Biol. Chem.
      272:14638-14642; Prado et al. [1998] J. Biol. Chem. 273:33548-33555). In this
      report, we mutate the remaining hydroxyl possessing residues located within the
      rBKB2R IC region. Exchange of S139A (IC2) or T239V (IC3) did not affect BK
      activated phosphatidylinositol (PI) turnover or receptor internalization.
      Chimeric exchange of the last 34 amino acids of BKB2R C-terminus with the
      corresponding 34 amino acids of the rat angiotensin II AT1a receptor (rAT1aR),
      both containing an S/T cluster, resulted in a mutant with normal endocytosis and
      BK activated PI turnover. A more selective chimera of these S/T clusters, with an
      exchange of BKB2R (333-351) with a rAT1aR fragment (326-342), resulted in a
      receptor with a retarded internalization but a normal BK activated PI turnover.
      Subsequent mutation of rBKB2R T344V showed little change in receptor uptake but a
      pronounced loss of BK activated PI turnover. The mutation of S335A, S341A, S348A,
      and S350A resulted in very poor receptor internalization and loss of activated PI
      turnover. Closer examination of this serine cluster illustrated that the
      replacement of S348A led to poor internalization; whereas the retention of S348
      and mutation of S341A resulted in a receptor with a much greater internalization
      than WT. These and other results suggest that the presence of S348 promotes
      internalization while the presence of S341 dampens it. Conversely, S341 and S350
      proved important for receptor signaling. In sum, our results illustrate that the
      distal C-terminus including its S/T cluster is important for both rBKB2R
      internalization and signal transduction. Individual S/T residues within this
      cluster appear involved in either signal transmission or receptor uptake
      capacity. However, replacement of the entire distal tail region with the
      corresponding rAT1aR sequence, also containing an S/T cluster, enables the
      BKB2R/AT1aR chimera to act in a very similar manner to wild type rBKB2R.

PMID- 11596114
TI  - Elfin is expressed during early heart development.
AB  - Elfin (previously named CLIM1) is a protein that possesses an N-terminal PDZ
      domain and a C-terminal LIM domain. It belongs to the family of Enigma proteins.
      Enigma proteins are a family of cytoplasmic proteins that contain an N-terminal
      PDZ domain and a series of C-terminal LIM domains. By virtue of these two protein
      interacting domains, Enigma proteins are capable of protein-protein interactions.
      It has been proposed that Enigma proteins may act as adapters between kinases and
      the cytoskeleton. We have previously shown that Elfin is most abundantly
      expressed in the heart and it colocalizes with alpha-actinin 2 at the Z-disks of
      the myocardium. In this report, Elfin was shown to localize at the actin stress
      fibers of myoblasts, as revealed by green fluorescent protein (GFP) tagging. In
      situ hybridization and immunostaining showed that Elfin expression begins at an
      early stage in mouse development and is present throughout the developing heart.
      Taken together, our experimental results suggest that Elfin may play an important
      role in myofibrillogenesis and heart development.

PMID- 11596115
TI  - Bcl-2 overexpression decreases BCNU sensitivity of a human glioblastoma line
      through enhancement of catalase activity.
AB  - The aim of this study was to evaluate the role of bcl-2 in 1,3-bis(2-chloroethyl)
      1-nitrosourea (BCNU) sensitivity of the ADFS human glioblastoma cell line in
      vitro and in vivo. To this end, the ADFS line expressing a low level of the bcl-2
      protein was transfected with a bcl-2 expression vector. We found that bcl-2
      overexpressing clones were less sensitive to in vitro BCNU treatment than the
      control clone. Cell cycle analysis demonstrated that while BCNU induced a
      consistent block in S/G2-M phases of the cell cycle in the control clone, it did
      not affect the cell cycle phase distribution of the two bcl-2 transfectants. The
      different sensitivity to BCNU was unrelated to the ability of bcl-2 to inhibit
      apoptosis, while bcl-2 appeared to protect bcl-2 transfectants from BCNU toxicity
      through an increase of catalase activity. The ability of the catalase inhibitor,
      sodium azide, to increase the BCNU sensitivity of the bcl-2 transfectants to
      levels of the BCNU-treated control clone substantiated the role of the catalase
      activity. The effect of bcl-2 in reducing sensitivity to BCNU was also confirmed
      by in vivo experiments. Xenografts of bcl-2 overexpressing tumors were less
      sensitive to BCNU treatment than xenografts originating from control cells.

PMID- 11596113
TI  - Estrogen regulation of human osteoblast function is determined by the stage of
      differentiation and the estrogen receptor isoform.
AB  - Although osteoblasts have been shown to respond to estrogens and express both
      isoforms of the estrogen receptor (ER alpha and ER beta), the role each isoform
      plays in osteoblast cell function and differentiation is unknown. The two ER
      isoforms are known to differentially regulate estrogen-inducible promoter
      reporter gene constructs, but their individual effects on endogenous gene
      expression in osteoblasts have not been reported. We compared the effects of 17
      beta-estradiol (E) and tamoxifen (TAM) on gene expression and matrix formation
      during the differentiation of human osteoblast cell lines stably expressing
      either ER alpha (hFOB/ER alpha 9) or ER beta (hFOB/ER beta 6). Expression of the
      appropriate ER isoform in these cells was confirmed by northern and western
      blotting and the responses to E in the hFOB/ER beta 6 line were abolished by an
      ER beta-specific inhibitor. The data demonstrate that (1) in both the hFOB/ER
      cell lines, certain responses to E or TAM (including alkaline phosphatase, IL-6
      and IL-11 production) are more pronounced at the late mineralization stage of
      differentiation compared to earlier stages, (2) E exerted a greater regulation of
      bone nodule formation and matrix protein/cytokine production in the ER alpha
      cells than in ER beta cells, and (3) the regulated expression of select genes
      differed between the ER alpha and ER beta cells. TAM had no effect on nodule
      formation in either cell line and was a less potent regulator of gene/protein
      expression than E. Thus, both the ER isoform and the stage of differentiation
      appear to influence the response of osteoblast cells to E and TAM.

PMID- 11596116
TI  - Salvia miltiorrhiza inhibits intimal hyperplasia and monocyte chemotactic protein
      1 expression after balloon injury in cholesterol-fed rabbits.
AB  - Antioxidants that prevent low density lipoproteins (LDL) from oxidation may
      inhibit atherosclerosis and post-angioplasty restenosis. Salvia miltiorrhiza (SM)
      has been shown to inhibit LDL oxidation and reduce atherosclerosis in cholesterol
      fed rabbits. The effects of SM on neointimal hyperplasia and monocyte chemotactic
      protein-1 (MCP-1) expression after balloon injury were studied. Male New Zealand
      white rabbits were fed a 2% cholesterol diet together with daily SM (4.8 gm/kg
      body wt.) treatment (SM; n=10) or without SM as a control (C; n=9) for 6 weeks.
      Probucol-treated (0.6 gm/kg body wt.) rabbits (P; n=9) were used as a positive
      control group. A balloon injury of the abdominal aorta was performed at the end
      of the third week. Aortas were harvested at the end of 6 weeks. The plasma
      cholesterol levels were lowered in SM group. The neointimal hyperplasia in
      abdominal aortas was significantly inhibited in SM group [neointima/media area
      ratio: 0.63+/-0.05 (SM) versus 0.78+/-0.05 (C); P < 0.05] and in P group [0.45+/
      0.02 (P) versus 0.78+/-0.05 (C); P < 0.05] when compared with C group. SM
      treatment significantly reduced MCP-1 mRNA and protein expression in balloon
      injured abdominal aorta. These inhibitory effects on intimal response after
      balloon injury might be attributed to antioxidant capacity and cholesterol
      lowering effect of SM. SM treatment may offer some protection against post
      angioplasty restenosis.

PMID- 11596117
TI  - Characterization of a 150 kDa accessory receptor for TGF-beta 1 on keratinocytes:
      direct evidence for a GPI anchor and ligand binding of the released form.
AB  - Transforming growth factor-beta (TGF-beta) is a key modulator of epidermal
      development and homeostasis, and has been shown to potently regulate keratinocyte
      migration and function during wound repair. There are three cloned TGF-beta
      receptors termed type I, type II, and type III that are found on most cell types.
      The types I and II are the signaling receptors, while the type III is believed to
      facilitate TGF-beta binding to the types I and II receptors. Recently, we
      reported that in addition to these receptors, human keratinocytes express a 150
      kDa TGF-beta 1 binding protein (r150) which forms a heteromeric complex with the
      TGF-beta signaling receptors. This accessory receptor was described as glycosyl
      phosphatidylinositol-specific anchored based on its sensitivity to
      phosphatidylinositol phospholipase C (PIPLC). In the present study, we
      demonstrate that the GPI-anchor is contained in r150 itself and not on a tightly
      associated protein and that it binds TGF-beta 1 with an affinity similar to those
      of the types I and II TGF-beta signaling receptors. Furthermore, the PIPLC
      released (soluble) form of this protein is capable of binding TGF-beta 1
      independently from the signaling receptors. In addition, we provide evidence that
      r150 is released from the cell surface by an endogenous phospholipase C. Our
      observation that r150 interacts with the TGF-beta signaling receptors, together
      with the finding that the soluble r150 binds TGF-beta 1 suggest that r150 in
      either its membrane anchored or soluble form may potentiate or antagonize TGF
      beta signaling. Elucidating the mechanism by which r150 functions as an accessory
      molecule in TGF-beta signaling may be critical to understanding the molecular
      mechanisms underlying the regulation of TGF-beta action in keratinocytes.

PMID- 11596118
TI  - Analysis of altered gene expression in rat soleus muscle atrophied by disuse.
AB  - The present study involved a global analysis of genes whose expression was
      modified in rat soleus muscle atrophied after hindlimb suspension (HS). HS muscle
      unloading is a common model for muscle disuse that especially affects antigravity
      slow-twitch muscles such as the soleus muscle. A cDNA cloning strategy, based on
      suppression subtractive hybridization technology, led to the construction of two
      normalized soleus muscle cDNA libraries that were subtracted in opposite
      directions, i.e., atrophied soleus muscle cDNAs subtracted by control cDNAs and
      vice versa. Differential screening of the two libraries revealed 34 genes with
      altered expression in HS soleus muscle, including 11 novel cDNAs, in addition to
      the 2X and 2B myosin heavy chain genes expressed only in soleus muscles after HS.
      Gene up- and down-regulations were quantified by reverse Northern blot and
      classical Northern blot analysis. The 25 genes with known functions fell into
      seven important functional categories. The homogeneity of gene alterations within
      each category gave several clues for unraveling the interplay of cellular events
      implied in the muscle atrophy phenotype. In particular, our results indicate that
      modulations in slow- and fast-twitch-muscle component balance, the protein
      synthesis/secretion pathway, and the extracellular matrix/cytoskeleton axis are
      likely to be key molecular mechanisms of muscle atrophy. In addition, the cloning
      of novel cDNAs underlined the efficiency of the chosen technical approach and
      gave novel possibilities to further decipher the molecular mechanisms of muscle
      atrophy.

PMID- 11596120
TI  - Basic principles of immunological surveillance of the normal central nervous
      system.
AB  - Unlike most bodily organs, the central nervous system (CNS) exists behind a blood
      tissue barrier designed to minimize the passage of cells and macromolecules into
      the neural parenchyma. Yet, the CNS is routinely and effectively surveyed by the
      immune system. This review examines the mechanisms and participants in this
      immunological surveillance mechanism. The nature of the healthy blood-brain
      barrier, factors modifying it, and its central position in determining the number
      and nature of leukocytes permitted to enter, are considered. In addition the role
      in surveillance played by lymphatic drainage, migrating T and B lymphocytes, and
      elements of the monocyte/macrophage/microglia family are considered. While all
      these participants are known to be important in responding to a CNS antigen
      and/or establishing a site of inflammation in the nervous system, they also are
      major elements in maintaining the homeostasis of the CNS and permitting the
      necessary immunological surveillance of that organ.

PMID- 11596121
TI  - New tools to trace populations of inflammatory cells in the CNS.
AB  - Cells of the central nervous system (CNS) and immune system communicate
      regularly. There is a constant surveillance of the intact, healthy CNS by
      activated T-cells, and massive infiltration of the CNS by immune cells under
      pathological conditions such as neurodegeneration or neuroinflammation. Labeling
      CNS-infiltrating T-cells is an essential tool to identify the signals and
      mechanisms, which mediate the interaction between immune cells and cells of the
      CNS. In this article, we will present an overview describing currently used
      cellular markers and demonstrate how these markers have contributed to our
      current knowledge of CNS inflammation and immune surveillance.

PMID- 11596122
TI  - Apoptosis of inflammatory cells in immune control of the nervous system: role of
      glia.
AB  - The elimination of inflammatory cells within the central nervous system (CNS) by
      apoptosis plays an important role in protecting the CNS from immune-mediated
      damage. T cells, B cells, macrophages, and microglia all undergo apoptosis in the
      CNS. The apoptotic elimination of CNS-reactive T cells is particularly important,
      as these cells can recruit and activate other inflammatory cells. T-cell
      apoptosis contributes to the resolution of CNS inflammation and clinical recovery
      from attacks of experimental autoimmune encephalomyelitis (EAE), an animal model
      of the demyelinating disease multiple sclerosis (MS). T-cell apoptosis in the CNS
      in EAE occurs in both an antigen-specific and an antigen-nonspecific manner. In
      antigen-specific T-cell apoptosis, it is proposed that T cells that recognize
      their antigen in the CNS, such as CNS-reactive T cells, are deleted by the
      process of activation-induced apoptosis after activation of the T-cell receptor.
      This may result from the ligation of T-cell death receptors (such as CD95 (Fas)
      or tumor necrosis factor (TNF) receptor 1) by CD95 ligand (CD95L) or TNF
      expressed by the same T cell or possibly by microglia, astrocytes or neurons.
      Inadequate costimulation of the T cell by antigen-presenting glial cells may
      render T cells susceptible to activation-induced apoptosis. T cells expressing
      CD95 may also die in an antigen-nonspecific manner after interacting with glial
      cells expressing CD95L. Other mechanisms for antigen-nonspecific T-cell apoptosis
      include the endogenous release of glucocorticosteroids, deprivation of
      interleukin-2, and the release of nitric oxide by macrophages or glia. Apoptosis
      of autoreactive T cells in the CNS is likely to be important in preventing the
      development of autoimmune CNS diseases such as MS.

PMID- 11596123
TI  - Glial cell influence on the human blood-brain barrier.
AB  - The blood-brain barrier (BBB) is a specialized structure of the central nervous
      system (CNS) that restricts immune cell migration and soluble molecule diffusion
      from the systemic compartment into the CNS. Astrocytes and microglia are resident
      cells of the CNS that contribute to the formation of the BBB. In this article, we
      consider the influence of these glial cells on the immune regulatory functions of
      the microvascular endothelium, with special emphasis on the human BBB. A series
      of in vitro studies demonstrate that soluble factors produced by glial cells,
      under basal culture conditions, help restrict development of inflammation within
      the CNS. These soluble factor effects include upregulating expression of
      molecules including HT7, UEA-1 lectin-binding sites, and angiotensin receptors
      that help define the phenotype of endothelial cells. These factors also induce
      tight junction formation between brain endothelial cells, contributing to the
      restricted permeability of the BBB. In contrast, these factors have little effect
      on expression of molecules by ECs that either promote lymphocyte migration, such
      as chemokines and adhesion molecules or molecules that are required for competent
      antigen presentation, such as MHC and co-stimulatory molecules. Glial cells that
      become activated in response to signals derived from the immune system or
      generated within the CNS, produce an array of inflammatory molecules that
      increase permeability and promote lymphocyte trafficking and persistence. These
      observations emphasize the bidirectional nature of neural-immune interactions;
      this dynamic system should be amenable to therapeutic interventions.

PMID- 11596124
TI  - Central nervous system perivascular cells are immunoregulatory cells that connect
      the CNS with the peripheral immune system.
AB  - Perivascular cells are a heterogeneous population found in the central nervous
      system (CNS) and the peripheral nervous system (PNS). Several terms are used for
      these cells, including perivascular cells, perivascular macrophages, perivascular
      microglia, fluorescent granular perithelial cells (FGP), or Mato cells. Different
      terminology used may reflect subpopulations of perivascular cells within
      different anatomic regions and experimental paradigms, neuropathological
      conditions, and species studied. Different terminology also points to the lack of
      clear consensus of what cells are perivascular cells in different disease states
      and models, especially with breakdown of the blood-brain barrier (BBB). Despite
      this, there is consensus that perivascular cells, although a minor component of
      the CNS, are important immunoregulatory cells. Perivascular cells are bone marrow
      derived, continuously turn over in the CNS, and are found adjacent to CNS
      vessels. Thus, they are potential sensors of CNS and peripheral immune system
      perturbations; are activated in models of CNS inflammation, autoimmune disease,
      neuronal injury and death; and are implicated as phagocytic and pinocytotic cells
      in models of stroke and hypertension. Recent evidence from our laboratory
      implicate perivascular cells as primary targets of human immunodeficiency virus
      (HIV) and simian immunodeficiency virus (SIV) infection in the CNS of humans and
      macaques. This article reviews current knowledge of perivascular cells, including
      anatomic location and nomenclature and putative immunoregulatory roles, and
      discusses new data on the infection of these cells by SIV, their accumulation
      after SIV infection, and a possible role of the immune system in SIV
      encephalitis.

PMID- 11596125
TI  - Immune function of microglia.
AB  - During the past decade, mechanisms involved in the immune surveillance of the
      central nervous system (CNS) have moved to the forefront of neuropathological
      research mainly because of the recognition that most neurological disorders
      involve activation and, possibly, dysregulation of microglia, the intrinsic
      macrophages of the CNS. Increasing evidence indicates that, in addition to their
      well-established phagocytic function, microglia may also participate in the
      regulation of non specific inflammation as well as adaptive immune responses.
      This article focuses on the signals regulating microglia innate immune functions,
      the role of microglia in antigen presentation, and their possible involvement in
      the development of CNS immunopathology.

PMID- 11596126
TI  - Immune function of astrocytes.
AB  - Astrocytes are the major glial cell within the central nervous system (CNS) and
      have a number of important physiological properties related to CNS homeostasis.
      The aspect of astrocyte biology addressed in this review article is the astrocyte
      as an immunocompetent cell within the brain. The capacity of astrocytes to
      express class II major histocompatibility complex (MHC) antigens and
      costimulatory molecules (B7 and CD40) that are critical for antigen presentation
      and T-cell activation are discussed. The functional role of astrocytes as immune
      effector cells and how this may influence aspects of inflammation and immune
      reactivity within the brain follows, emphasizing the involvement of astrocytes in
      promoting Th2 responses. The ability of astrocytes to produce a wide array of
      chemokines and cytokines is discussed, with an emphasis on the immunological
      properties of these mediators. The significance of astrocytic antigen
      presentation and chemokine/cytokine production to neurological diseases with an
      immunological component is described.

PMID- 11596127
TI  - Control of glial immune function by neurons.
AB  - The immune status of the central nervous system (CNS) is strictly regulated. In
      the healthy brain, immune responses are kept to a minimum. In contrast, in a
      variety of inflammatory and neurodegenerative diseases, including multiple
      sclerosis, infections, trauma, stroke, neoplasia, and Alzheimer's disease, glial
      cells such as microglia gain antigen-presenting capacity through the expression
      of major histocompatibility complex (MHC) molecules. Further, proinflammatory
      cytokines, such as tumor necrosis factor-alpha (TNF), interleukin-1beta (IL
      1beta), and interferon-gamma (IFN-gamma), as well as chemokines, are synthesized
      by resident brain cells and T lymphocytes invade the affected brain tissue. The
      proinflammatory cytokines stimulate microglial MHC expression in the lesioned CNS
      areas only. However, the induction of brain immunity is strongly counterregulated
      in intact CNS areas. For instance, recent work demonstrated that microglia are
      kept in a quiescent state in the intact CNS by local interactions between the
      microglia receptor CD200 and its ligand, which is expressed on neurons. Work done
      in our laboratory showed that neurons suppressed MHC expression in surrounding
      glial cells, in particular microglia and astrocytes. This control of MHC
      expression by neurons was dependent on their electrical activity. In brain tissue
      with intact neurons, the MHC class II inducibility of microglia and astrocytes by
      the proinflammatory cytokine IFN-gamma was reduced. Paralysis of neuronal
      electric activity by neurotoxins restored the induction of MHC molecules on
      microglia and astrocytes. Loss of neurons or their physiological activity would
      render the impaired CNS areas recognizable by invading T lymphocytes. Thus,
      immunity in the CNS is inhibited by the local microenvironment, in particular by
      physiologically active neurons, to prevent unwanted immune mediated damage of
      neurons.

PMID- 11596128
TI  - Glial cells as targets for cytotoxic immune mediators.
AB  - Oligodendrocytes and Schwann cells are the glia principally responsible for the
      synthesis and maintenance of myelin. Damage may occur to these cells in a number
      of conditions, but perhaps the most studied are the idiopathic inflammatory
      demyelinating diseases, multiple sclerosis in the CNS, and Guillain-Barre
      syndrome and its variants in the peripheral nervous system (PNS). This article
      explores the effects on these cells of cytotoxic immunological and inflammatory
      mediators: similarities are revealed, of which perhaps the most important is the
      sensitivity of both Schwann cells and oligodendrocytes to many such agents. This
      area of research is, however, characterised and complicated by numerous and often
      very substantial inter-observer discrepancies. Marked variability in cell culture
      techniques, and in assays of cell damage and death, provide artifactual
      explanations for some of this variability; true inter-species differences also
      contribute. Not the least important conclusion centres on the limited capacity of
      in vitro studies to reveal disease mechanisms: cell culture findings merely
      illustrate possibilities which must then be tested ex vivo using human tissue
      samples affected by the relevant disease.

PMID- 11596129
TI  - Glial expression of tumor necrosis factor in transgenic animals: how do these
      models reflect the "normal situation"?
AB  - Recent progress in the field of experimental genetics, which enables the
      selective and conditional ablation or dysregulation in the expression of specific
      genes in mice, and its application to the study of experimentally inducible
      models for human disease, have contributed enormously to our understanding of the
      molecules and mechanisms that underlie autoimmunity and inflammation in the CNS.
      This article describes the lessons learned from the application of such
      technology to the study of the tumor necrosis factor-alpha (TNF) ligand/receptor
      system in the CNS. Important roles for TNF and its two membrane-bound receptors
      in the initiation and support of CNS inflammation, the development of CNS
      autoimmunity, and possibly in the resolution of T-cell-mediated disease, as well
      as their implications for our understanding of the "normal" cellular and
      molecular mechanisms that underlie CNS pathology, are discussed.

PMID- 11596130
TI  - T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental
      autoimmune encephalomyelitis and multiple sclerosis.
AB  - The identification of myelin oligodendrocyte glycoprotein (MOG) as a target for
      autoantibody-mediated demyelination in experimental autoimmune encephalomyelitis
      (EAE) resulted in the re-evaluation of the role of B cell responses to myelin
      autoantigens in the immunopathogenesis of multiple sclerosis. MOG is a central
      nervous system specific myelin glycoprotein that is expressed preferentially on
      the outermost surface of the myelin sheath. Although MOG is only a minor
      component of CNS myelin it is highly immunogenic, inducing severe EAE in both
      rodents and primates. In rat and marmoset models of MOG-induced EAE demyelination
      is antibody-dependent and reproduces the immunopathology seen in many cases of
      MS. In contrast, in mice inflammation in the CNS can result in demyelination in
      the absence of a MOG-specific B cell response, although if present this will
      enhance disease severity and demyelination. Clinical studies indicate that
      autoimmune responses to MOG are enhanced in many CNS diseases and implicate MOG
      specific B cell responses in the immunopathogenesis of multiple sclerosis. This
      review provides a summary of our current understanding of MOG as a target
      autoantigen in EAE and MS, and addresses the crucial question as to how immune
      tolerance to MOG may be maintained in the healthy individual.

PMID- 11596131
TI  - Inflammation in the nervous system: the human perspective.
AB  - Many basic aspects of brain inflammation, recently disclosed in experimental
      models, are reflected in the pathology of human inflammatory brain diseases.
      Examples include the key role of T lymphocytes in immune surveillance and in the
      regulation of the inflammatory response, the essential contributions of adhesion
      molecules, proinflammatory cytokines, chemokines, and proteases in the
      recruitment of inflammatory cells into the nervous tissue, the modulating effect
      of glia cells on the inflammatory process and the termination of T-cell-mediated
      inflammation by apoptotic cell death. Despite this progress in our understanding
      of the pathogenesis of brain inflammation, there are still major unresolved
      questions. Because of technical constraints, most of our knowledge on central
      nervous system inflammation so far relates to the role of a specific T-cell
      subset, the so-called T-helper-1 cells. Other T-cell subsets, in particular
      cytotoxic class I MHC-restricted T lymphocytes, however, appear to be of major
      importance in human disease. Furthermore, the detailed mechanisms, which are
      responsible for the profound differences in the patterns of tissue damage in
      different human inflammatory brain diseases, such as multiple sclerosis or
      various forms of virus encephalitis, are largely unresolved. We discuss the open
      questions to be addressed in the future, which, when answered, may help to design
      novel therapeutic strategies.

PMID- 11596136
TI  - A rapid, automated approach to optimisation of multiple reaction monitoring
      conditions for quantitative bioanalytical mass spectrometry.
AB  - An improvement to the procedure for the rapid optimisation of mass spectrometry
      (PROMS), for the development of multiple reaction methods (MRM) for quantitative
      bioanalytical liquid chromatography/tandem mass spectrometry (LC/MS/MS), is
      presented. PROMS is an automated protocol that uses flow-injection analysis (FIA)
      and AppleScripts to create methods and acquire the data for optimisation. The
      protocol determines the optimum orifice potential, the MRM conditions for each
      compound, and finally creates the MRM methods needed for sample analysis. The
      sensitivities of the MRM methods created by PROMS approach those created
      manually. MRM method development using PROMS currently takes less than three
      minutes per compound compared to at least fifteen minutes manually. To further
      enhance throughput, approaches to MRM optimisation using one injection per
      compound, two injections per pool of five compounds and one injection per pool of
      five compounds have been investigated. No significant difference in the optimised
      instrumental parameters for MRM methods were found between the original PROMS
      approach and these new methods, which are up to ten times faster. The time taken
      for an AppleScript to determine the optimum conditions and build the MRM methods
      is the same with all approaches.

PMID- 11596143
TI  - Negative ion fragmentations of deprotonated peptides: backbone cleavages directed
      through both Asp and Glu.
AB  - The collision-induced spectra of [M - H](-) ions of a variety of natural and
      synthetic amphibian peptides containing Asp and/or Glu exhibit characteristic
      gamma backbone cleavage ions that identify the positions of these residues in the
      peptide. A theoretical study suggests that the Glu cleavage involves an S(N)i
      reaction of the carboxylate anion from the Glu alpha side chain to form a
      deprotonated cyclic lactone. The presence of either Asp or Glu or other residues
      that effect pronounced side-chain cleavages (e.g. Ser or Thr) results in the
      normal alpha and beta backbone cleavages being reduced in comparison to those
      cleavages which originate from side chains.

PMID- 11596145
TI  - Distribution of sex steroid hormone receptors in the avian brain: functional
      implications for neural sex differences and sexual behaviors.
AB  - Developmental and seasonal changes in the production of androgens, estrogens, and
      progestins seem to control sex-specific differentiation and seasonal changes in
      appetitive and consummatory sexual behaviors of birds. This results in profound
      sex differences in the quality (sex-specific) or quantity (sex-typical) of
      behaviors such as courtship, territoriality, or copulation. Steroids affect the
      brain by binding to intracellularly located receptors. The same brain areas
      express androgen, estrogen, and progesterone receptors in male and female brains.
      Sex differences in these genetically determined patterns occur in the size of
      neuron populations that intrinsically express sex steroid receptors. Further
      permanent sex differences are subsequent to degenerative fates of receptor
      expressing neuron populations during ontogeny. Transient sex differences in
      receptor expression appear to be due to area-specific up- and down-regulation of
      receptor levels, reflecting transient changes in the level of circulating
      steroids, changes in environmental conditions, or in the physiological status of
      the individuals. In particular, intrinsic sex differences in the expression
      pattern of sex steroid receptors and steroid-independent regulation of the
      expression level of these receptors in the brain are limiting mechanisms for
      gonad-dependent sexual development and activities.

PMID- 11596147
TI  - Gender-related changes in the avian vasotocin system during ontogeny.
AB  - The arginine vasotocin (AVT) system of the avian brain includes a sexually
      dimorphic part that extends from the caudal part of preoptic region through the
      medial part of the bed nucleus of stria terminalis (BSTm) to the lateral septum.
      It is composed of the parvocellular neurons located in the BSTm and the dense
      innervation of the medial preoptic region and lateral septum. In this part of the
      brain, AVT expression is stronger in males than in females in a few bird species
      investigated to date. This review focuses on the ontogeny of sexual differences
      in the vasotocinergic system of two gallinaceous species, domestic chicken and
      Japanese quail, and on the role of gonadal hormones in organizing during
      development and maintaining in adulthood these differences. Parvocellular AVT
      neurons become discernible in the BSTm of males and females during the second
      half of embryonic development. These cells undergo a profound and irreversible
      sexual differentiation during ontogenetic development. Recent findings
      demonstrate a dual role of estrogens in the organization and activation of sex
      differences in the AVT system. During the embryonic period of ontogeny, estrogens
      differentiate the AVT system in a sexually dimorphic manner in parallel with the
      differentiation of sexual behavior, while in adulthood estrogens, locally
      produced from testosterone in the male brain, activate AVT synthesis in the BSTm.
      The sexually dimorphic part of the AVT system is sensitive to a number of abiotic
      factors such as light, temperature, and water availability. It is suggested that
      sex dimorphic vasotocinergic systems could be implicated in processes of social
      recognition in various behavioral contexts.

PMID- 11596146
TI  - Changes in central steroid receptor expression, steroid synthesis, and
      dopaminergic activity related to the reproductive cycle of the ring dove.
AB  - This review examines possible neural mechanisms involved in the expression of
      parental behavior in the ring dove, Streptopelia risoria. This avian species has
      proved an excellent animal model for studies concerning endocrine-behavior
      interactions for many years. Studies were performed to localize the expression of
      central androgen and progesterone receptor in both sexes. Expression of androgen
      receptor (androgen receptor immunoreactivity, AR-ir) was widespread but
      increased, similarly in both sexes, with increasing day-length. Progesterone
      receptor-immunoreactivity (PR-ir) was more localized in several discrete areas of
      the hypothalamus. Similarly, no sex differences were observed in PR-ir, and
      expression increased in birds maintained on long days. AR-ir demonstrated
      dramatic changes over the breeding cycle, being greatest in courting birds and
      almost undetectable in parenting birds of both sexes brooding their young. PR-ir
      showed a differential expression over the breeding cycle relative to its
      hypothalamic localization. PR-ir decreased in the tuberal hypothalamic area in
      brooding birds of both sexes; whereas in the preoptic area, PR-ir was maintained.
      Significant increases in dopaminergic activity during the parenting phase of the
      breeding cycle occurred in specific neural regions including the PVM and DMA.
      Studies demonstrated the ability of the diencephalon of both sexes of the ring
      dove brain to synthesize progesterone, with indications that in the male brooding
      dove, synthesis is increased. Finally, a model is presented that proposes a
      mechanism whereby these central systems may interact to result in the expression
      of full parental behavior in both sexes of the ring dove.

PMID- 11596148
TI  - Sexual differences and effect of photoperiod on melatonin receptor in avian
      brain.
AB  - Several data suggest that melatonin may influence avian reproduction by acting at
      the level of the hypothalamic-hypophisial-gonadal axis, and/or on neural circuits
      controlling reproductive behaviours. The action of melatonin is exerted through
      specific receptors whose distribution and pharmacological properties have been
      extensively investigated. This review will focus on the distribution, sexual
      dimorphism, and dependence upon the photoperiod of melatonin binding sites in
      avian species with a special emphasis on Japanese quail. Melatonin receptors are
      widely distributed in avian brain. They are mostly present in the visual pathways
      of all the investigated species and in the song controlling nuclei of oscine
      birds. Sexual dimorphism of melatonin binding sites (higher density in males than
      in females) was detected in some telencephalic nuclei of songbirds, in the visual
      pathways, and in the preoptic area of quail. The last region plays a key role in
      the activation of male quail copulatory behaviour and it hosts a large population
      of gonadotropin-releasing hormone-containing neurons. Sexual dimorphism of
      melatonin-binding sites in the above-mentioned regions suggests a differential
      role for this hormone in the modulation of visual perception, gonadotropin
      production, and seasonally activated behaviours in male and female quail. Further
      studies are necessary to understand interrelationships among photic cues, gonadal
      steroids, density, and sexually dimorphic distribution of melatonin receptors.

PMID- 11596149
TI  - Apolipoprotein E immunoreactivity in neurons and neurofibrillary degeneration of
      aged non-demented and Alzheimer's disease patients.
AB  - Apolipoprotein E (ApoE) genotype is a risk factor for Alzheimer's disease (AD)
      but its relationship with neurofibrillary degeneration remains obscure. To
      further analyze this relationship, hippocampal, entorhinal, temporopolar, and
      insular cortices of 10 non-demented and 7 Alzheimer disease brains were studied
      with both light and electron microscopy. Focus was directed on pretangles and
      neurons starting to accumulate tangles. ApoE immunolabeling in neurons and
      tangles was independent of ApoE individual genotype. The majority of the neurons
      in all of the brains were ApoE-negative, but virtually every brain also contained
      groups of ApoE-immunoreactive neurons, with diffuse cytoplasmic labeling. Most of
      the ApoE-positive tangles were extracellular, but a few tangles were shown to be
      intraneuronal when studied ultrastructurally. No ApoE immunoreactivity was found
      in neuropil threads, as well as in neurites associated with senile plaques.
      Double protocols with both AT-8 and anti-ApoE antibodies, performed to determine
      whether ApoE-positive neurons were pretangle neurons, did not detect cytoplasmic
      AT-8 in ApoE-positive neurons. Though careful electron microscopy studies found
      ApoE reaction product in an occasional ApoE-positive pretangle-like neuron and a
      few intracellular tangles, these findings do not support that ApoE is necessary
      for the accumulation of hyperphosphorylated tau protein. The more consistent
      colocalization of anti-ApoE and AT-8 in extracellular tangles reveals that ApoE
      mainly binds to tangles once they are in the extracellular space, in a manner
      similar to that described for amyloid fibrils.

PMID- 11596150
TI  - New perspectives in lymphangiogenesis research.

PMID- 11596151
TI  - Markers for the lymphatic endothelium: in search of the holy grail?
AB  - The ability to discriminate reliably at the histological level between blood and
      lymphatic microcapillaries would greatly assist the study of a number of
      biological and pathological questions and may also be of clinical utility. A
      structure-function comparison of these types of microcapillary suggests that
      differences which could function as markers to allow discrimination between blood
      and lymphatic endothelium should exist. Indeed, to date a variety of such markers
      have been proposed, including basement membrane components, constituents of
      junctional complexes such as desmoplakin and enzymes such as 5'-nucleotidase.
      Additionally, a variety of cell surface molecules are thought to be
      differentially expressed, including PAL-E, VEGFR-3, podoplanin, and LYVE-1.
      Several of the lymphatic markers proposed in the literature require further
      characterization to demonstrate fully their lymphatic specificity and some have
      proven not to be reliable. The relative merits and drawbacks of each of the
      proposed markers is discussed.

PMID- 11596152
TI  - Histochemical analysis of lymphatic endothelial cells in lymphostasis.
AB  - The ultrastructure of endothelial cells of intestinal lymphatics and the thoracic
      duct (TD) and the relation to lymphostasis were examined in rats and monkeys.
      Localization of 5'-nucleotidase (5'-Nase) and endothelial nitric oxide synthase
      (eNOS) was studied. In normal lymphatic endothelial cells, 5'-Nase reaction
      product was evenly deposited on the cell surface in vivo and on cultured TD
      endothelial cells (TDECs), whereas eNOS was evenly distributed throughout the
      nucleus and cytoplasm. TDECs had a long filamentous process extending towards the
      subendothelial extracellular matrix but became flat and regular within 30-40
      minutes after gastric perfusion with olive oil. According to their electron
      density, two types of cells were found in the TD endothelial layer. The cells
      with low electron-density exhibited stronger 5'-Nase activity. Valves were
      bicuspid formations and the valvular endothelial surface of the convex side
      showed weaker 5'-Nase activity than the concave side. During TD blockage-induced
      lymphostasis in rats, the 5'-Nase product was almost not discernible in the TDECs
      within 2 weeks. Larger vesicles were found in the endothelial cytoplasm of the
      ligated TD. Their number decreased after 6-12 weeks. The small intestinal
      lymphatics in the mucosa and submucosa were dilated, with numerous open
      intercellular junctions. The endothelial lining appeared to have reduced
      activities for 5'-Nase and eNOS in 9 of 11 experimental animals. The results
      indicated that the inability of the open intercellular junctions, normally
      working as one-way endothelial flap valves, may be a key morphological feature
      after TD blockage. Reduced eNOS and 5'-Nase may functionally influence
      contractile activity and transport capability of the lymphatic vessels in the
      lymphostasis.

PMID- 11596154
TI  - Lymphatic function, lymphangiogenesis, and cancer metastasis.
AB  - The lymphatic system serves as the primary route for the metastasis of many
      cancers and the extent of lymph node involvement is the most important indicator
      of tumor aggressiveness. Despite the apparent importance of the lymphatic vessels
      for tumor dissemination, it has remained unclear whether activation of lymphatic
      endothelial cells may affect tumor progression and metastasis and the molecular
      mechanisms of lymphangiogenesis are just beginning to be elucidated. This
      overview describes the unique structural and functional characteristics of the
      lymphatic vessels that render them particularly suitable for invasion by tumor
      cells and for their efficient transport to lymph nodes. Recent evidence indicates
      occurrence of tumor lymphangiogenesis and its correlation with metastasis.
      Molecular regulation of tumor lymphangiogenesis, its significance for tumor
      metastasis, and implications for cancer therapy are discussed.

PMID- 11596153
TI  - Development of the avian lymphatic system.
AB  - Recently, highly specific markers of the lymphatic endothelium have been found
      enabling us to reinvestigate the embryonic origin of the lymphatics. Here we
      present a review of our studies on the development of the lymphatic system in
      chick and quail embryos. We show that the lymphatic endothelium is derived from
      two sources: the embryonic lymph sacs and mesenchymal lymphangioblasts.
      Proliferation studies reveal a BrdU-labeling index of 11.5% of lymph sac
      endothelial cells by day 6.25, which drops to 3.5% by day 7. Lymphangioblasts are
      able to integrate into the lining of lymph sacs. Lymphatic endothelial cells
      express the vascular endothelial growth factor (VEGF) receptors-2 and -3. Their
      ligand, VEGF-C, is expressed almost ubiquitously in embryonic and fetal tissues.
      Elevated expression levels are found in the tunica media of large blood vessels,
      which usually serve as major routes for growing lymphatics. The homeobox gene,
      Prox1, is expressed in lymphatic but not in blood vascular endothelial cells
      throughout all stages examined, namely, in developing lymph sacs of day 6 embryos
      and in lymphatics at day 16. Experimental studies show the existence of
      lymphangioblasts in the mesoderm, a considerable time before the development of
      the lymph sacs. Lymphangioblasts migrate from the somites into the somatopleure
      and contribute to the lymphatics of the limbs. Our studies indicate that these
      lymphangioblasts already express Prox1.

PMID- 11596155
TI  - Interaction of rat tumor cells with blood vessels and lymphatics of the avian
      chorioallantoic membrane.
AB  - It has generally been assumed that tumors do not induce lymphangiogenesis and
      only very recently animal models have been presented showing tumor-induced
      lymphangiogenesis. We have grown two types of rat tumor cells, 10AS pancreatic
      carcinoma and C6 glioma cells, on the chorioallantoic membrane (CAM) of chick and
      quail embryos. The suspended tumor cells rapidly formed solid tumors which
      invaded the CAM and were vascularized by CAM vessels. When grown on the CAM of
      quail embryos intratumoral endothelial cells could be specifically stained with
      the QH1 antibody. In C6 gliomas the vascular pattern was more regular than in
      10AS carcinomas. The vessels often grew radially into the glioma and many of them
      were invested by smooth muscle alpha-actin-positive periendothelial cells.
      Lymphatics, which were identified by vascular endothelial growth factor receptor
      3 (VEGFR-3) in situ hybridization were absent from C6 gliomas, although a weak
      expression of the lymphangiogenic growth factor, VEGF-C, could be detected in the
      C6 cells by Northern blot analysis. In contrast, 10AS cells, which expressed high
      levels of VEGF-C, induced ingrowth of lymphatics into the tumors, with BrdU
      labeling rates of about 9% of lymphatic endothelial cells. Our studies
      demonstrate the heterogeneity of interactions of tumor cells with blood vessels
      and lymphatics and show that sufficient quantities and/or quality of
      lymphangiogenic growth factors are crucial for the induction of lymphatics in
      tumors.

PMID- 11596156
TI  - Lymphatic versus blood vascular endothelial growth factors and receptors in
      humans.
AB  - Three different growth factor systems have been described acting via endothelial
      cell-specific receptor tyrosine kinases (RTKs). These are vascular endothelial
      growth factors (VEGFs), angiopoietins, and ephrins. Recent studies on gene
      targeting suggest that they play critical roles in embryonic development and
      contribute to the integrity and responses to environmental factors in the adult
      vasculature. Coagulation, inflammation, immune response regulation, vascular
      tone, stromal component synthesis, and angiogenesis are all dependent on the
      physiological and pathological events that affect endothelial cells in the heart,
      arteries, veins, and lymphatic vessels. Angiogenesis, the formation of new blood
      vessels from preexisting ones, takes place in adults only during hormonal control
      of female reproduction. All other activation of angiogenesis in adulthood occurs
      in response to injury or pathological processes such as tumorigenesis, diabetes,
      or inflammatory conditions. Insufficient growth of collateral vessels is a major
      problem in atherosclerotic cardiovascular disease. Controlled stimulation of
      angiogenesis would be of therapeutic value. Lymphangiogenesis, the mechanisms
      involved in the development of lymphatic vessels, was studied intensively nearly
      a century ago, although since then it has been neglected, perhaps because, unlike
      the disorders of blood vessels, those of the lymphatic vessels are seldom life
      threatening. Interrupting this one-way system can cause severe disorders,
      including liver dysfunction, genetic disease (e.g., Milroys disease), and
      degenerative disease (e.g., primary lymphangiosclerosis). Recently, novel growth
      factors, receptors, cell surface proteins, and transcription factors have been
      found which play a role in the lymphatic endothelium. These are VEGF-C, VEGF-D,
      VEGFR-3, LYVE-1, podoplanin, and Prox-1. Until recently lymphatic vessels have
      been difficult to study due to a lack of appropriate tools. Monoclonal antibodies
      raised against VEGFR-3 and against its ligands, VEGF-C and VEGF-D, have offered
      an insight into expression studies in tissues. In this review, we summarize the
      recent data on VEGFs in the human vasculature.

PMID- 11596157
TI  - Lymphangiogenesis and lymphangiodysplasia: from molecular to clinical lymphology.
AB  - The lymph vascular system parallels the blood vasculature and as one of its key
      functions returns liquid and solutes to the bloodstream, including macromolecules
      that have escaped from blood capillaries and entered the interstitium. In
      conjunction with interspersed lymph nodes and lymphoid organs, the lymphatic
      vasculature also acts as a conduit for trafficking immune cell populations.
      Echoing the explosion of knowledge about blood vessel angiogenesis (properly
      termed "hemangiogenesis"), the past two decades have also witnessed a series of
      significant, yet less-noticed discoveries bearing on "lymphangiogenesis," along
      with delineation of the spectrum of lymphedema-angiodysplasia syndromes. Failure
      of lymph transport promotes a brawny proteinaceous edema of the affected limb,
      organ, or serous space that is disfiguring, disabling, and on occasion even life
      threatening. Key members of the vascular endothelial growth factor (VEGF) and
      angiopoietin families of vascular growth factors (and their corresponding
      tyrosine kinase endothelial receptors) have been identified which preferentially
      influence lymphatic growth and, when manipulated in genetically engineered murine
      models, produce aberrant "lymphatic phenotypes." Moreover, mutations in VEGF
      receptor and forkhead family developmental genes have now been linked and
      implicated in the pathogenesis of two familial lymphedema-angiodysplasia
      syndromes. Thus, recent advances in "molecular lymphology" are elucidating the
      poorly understood development, physiology, and pathophysiology of the neglected
      lymphatic vasculature. In combination with fresh insights and refined tools in
      "clinical lymphology," these advances should lead not only to earlier detection
      and more rational classification of lymphatic disease but also to better
      therapeutic approaches, including designer drugs for lymphangiostimulation and
      lymphangioinhibition and gene therapy to modulate lymphatic growth.

PMID- 11596158
TI  - Presence of cystic fibrosis-related diabetes mellitus is tightly linked to poor
      lung function in patients with cystic fibrosis: data from the European
      Epidemiologic Registry of Cystic Fibrosis.
AB  - Data derived from a cross-sectional analysis of 7,566 patients stratified into
      six age groups were used to compare lung function, body mass index (BMI), and
      weight for age in patients with and without cystic fibrosis-related diabetes
      mellitus (CFDM). The presence of CFDM was tightly linked to poor lung function,
      regardless of age. The mean value of FEV(1) % predicted in the age groups < 10,
      10-< 15, 15-< 20, 20-< 25, 25-< 30, and 30 years or older were 87%, 77%, 69%,
      58%, 55%, and 53% in the nondiabetic cystic fibrosis (CF) patients as compared to
      79%, 66%, 55%, 49%, 46%, and 44% in the diabetic CF patients. BMI and weight for
      age were also lower in diabetic than nondiabetic CF patients in all age groups,
      except for BMI in the youngest patients. The difference in lung function and in
      nutritional parameters between diabetic and nondiabetic CF patients was not
      linked to presence or absence of any specific pathogen in the lower respiratory
      tract. These results confirm and extend those of earlier studies in smaller
      numbers of patients, and they clearly identify CFDM as a powerful determinant of
      severe lung disease and reduced survival in patients with CF and diabetes
      mellitus.

PMID- 11596159
TI  - Diabetes mellitus and cystic fibrosis: comparison of clinical parameters in
      patients treated with insulin versus oral glucose-lowering agents.
AB  - The prevalence of cystic fibrosis-related diabetes melltitus (CFRD) is increasing
      as patients with cystic fibrosis (CF) live longer. Because patients with CFRD are
      insulin-deficient, the standard medical treatment is exogenous insulin.
      Sulfonylureas enhance insulin secretion by acting on a specific islet beta cell
      receptor. No data are available about the outcome of sulfonylurea treatment vs.
      insulin treatment. In this retrospective study, data from 45 patients with CFRD
      were analyzed regarding their clinical outcome as it related to the treatment
      protocol. The duration of DM treatment was 7.6 +/- 4.6 years in the insulin
      treated group and 3.5 +/- 2.0 years in the sulfonylurea group (n.s.). The age of
      CFRD diagnosis was significantly earlier in patients treated with insulin (n =
      34) than in the patients treated with sulfonylurea (n = 11) (16.4 +/- 3.6 vs.
      24.2 +/- 4.8 years, P < 0.001). No statistical differences were found between the
      two groups in the time of CF diagnosis, the most recent forced expired volume in
      1 sec, forced vital capacity, Shwachman score, hemoglobin A(1C) levels, or weight
      for height index at the end of the study. Our data suggest that a subgroup of
      CFRD patients can be managed for a number of years with sulfonylurea, and that
      the clinical outcome was not different in this group compared with the insulin
      treated patients.

PMID- 11596160
TI  - Early pulmonary infection, inflammation, and clinical outcomes in infants with
      cystic fibrosis.
AB  - A thorough understanding of the early natural history of cystic fibrosis (CF)
      lung disease is critical for the development of effective interventions in the
      youngest patients. We assessed the evolution of pulmonary infection,
      inflammation, and clinical course among 40 infants over a 2-year period through
      annual bronchoalveolar lavage (BAL) for culture and measurements of pro- and anti
      inflammatory cytokines, semiannual infant pulmonary function testing, and
      quarterly clinical evaluations. Both the prevalence of CF pathogens and their
      density in BAL fluid increased with age. Infants had neutrophilic lower airway
      inflammation and elevated IL-8 concentrations independent of whether CF pathogens
      were recovered. Total leukocyte and neutrophil densities and IL-8 concentrations
      increased with density of CF pathogens in BAL fluid, whether the isolated
      organism was P. aeruginosa or another pathogen. IL-10 concentrations were similar
      in CF subjects and non-CF historical controls. Infants generally had suboptimal
      growth (low weight and height percentiles) and obstructive lung disease
      (decreased expiratory flows and air trapping). Subjects from whom CF pathogens
      were isolated at > 10(5) cfu/mL had the worst air trapping and lowest Brasfield
      chest X-ray scores. Our findings provide a foundation for future studies of early
      intervention in CF lung disease, including antimicrobial and anti-inflammatory
      therapy.

PMID- 11596161
TI  - Persistent adenoviral infection and chronic obstructive bronchitis in children:
      is there a link?
AB  - Chronic obstructive bronchitis with inadequate response to inhaled steroid and
      bronchodilator therapy is a rather rare disorder in children. Persistence of an
      adenoviral infection has been described as a possible cause of unremitting airway
      obstruction. We studied a group of 11 children with the clinical feature of
      chronic bronchial obstruction. A high-resolution computed tomography (HR-CT) scan
      was performed and typically showed hyperinflation and ground-glass-like
      opacities. All children underwent either bronchoscopic transbronchial or open
      lung biopsy. Biopsy specimens were stained with monoclonal antibodies detecting
      adenoviral antigen and analyzed by light-microscopy. Bronchoalveolar lavage (BAL)
      fluid was cultured for adenovirus, and antigen detection tests were performed.
      While some children had a history of proven adenoviral infection at the onset of
      their disease, in none of the cases could a persistence of adenovirus be shown.
      We conclude that adenoviral infection might act as a starter of chronic
      obstructive bronchitis in children, but that pathogenetic mechanisms other than
      persistent infection must be responsible for the chronicity of the disease.

PMID- 11596162
TI  - Comparison of high-frequency chest wall oscillation and oscillating positive
      expiratory pressure in the home management of cystic fibrosis: a pilot study.
AB  - Enhanced airway clearance is thought to result in better-maintained pulmonary
      function in cystic fibrosis (CF). Postural drainage, percussion, and vibration
      (PDPV) have been the primary airway clearance technique (ACT) employed in CF for
      over 40 years. Two new airway clearance modalities are high-frequency chest wall
      oscillation (HFCWO) and oscillating positive expiratory pressure (OPEP). This
      pilot study was undertaken to evaluate the efficacy of these techniques during
      home use, assess patient satisfaction with them as compared to PDPV, and assess
      the feasibility of performing a definitive comparative trial. The prospective,
      randomized, multicenter crossover trial was conducted at three urban academic CF
      Care Centers. Twenty-nine CF patients, 9-39 years of age, participated. Subjects
      performed 4 weeks each of HFCWO and OPEP following 2-week lead-in/washout
      periods. Spirometry, lung volumes, National Institutes of Health and Petty
      Scores, and a satisfaction survey were performed at baseline and after each
      treatment period. An ACT preference survey was completed at the conclusion of the
      study. Twenty-four subjects completed both therapies. There were no statistically
      significant differences between therapies for spirometry, lung volumes, or
      clinical scores. No significant safety issues arose during the study period.
      Compliance between therapies was similar. Significant differences among therapies
      existed in patient satisfaction. Given a choice of therapy, 50% of subjects chose
      HFCWO, 37% OPEP, and 13% PDPV. This study suggests that HFCWO and OPEP are safe
      and as effective as patients' routine therapies when used for airway clearance in
      a home setting. Patient satisfaction and preference differ among ACTs and should
      be considered when prescribing home therapy. A definitive, multi-center,
      comparative study evaluating long-term efficacy of these techniques is feasible.

PMID- 11596163
TI  - Risks and complications of nonbronchoscopic bronchoalveolar lavage in a pediatric
      intensive care unit.
AB  - This paper aims to document the risks and complications of nonbronchoscopic
      bronchoalveolar lavage (NB-BAL) in 35 mechanically ventilated patients with
      diffuse severe pneumonia in a single pediatric intensive care unit. A prospective
      collection of data on patients' ventilatory settings and oxygen requirements
      before NB-BAL, and oxyhemoglobin saturations and heart rate readings before,
      during, and after the procedure were taken on each patient. The major
      complication of NB-BAL was arterial desaturation, which was more severe and
      prolonged in patients with poor oxygenation indices and PaO(2)/FiO(2) ratios. The
      diagnostic yield of the procedure was high at 69%.

PMID- 11596164
TI  - A debate on why my state (province) should or should not conduct newborn
      screening for cystic fibrosis (14th Annual North American Cystic Fibrosis
      Conference).

PMID- 11596165
TI  - Development of progressive pulmonary interstitial and intra-alveolar cholesterol
      granulomas (PICG) associated with therapy-resistant chronic systemic juvenile
      arthritis (CJA).
AB  - A girl aged 5 years with therapy-resistant chronic systemic juvenile arthritis
      (CJA) developed progressive fibrosing lung disease. Histology of an open lung
      biopsy revealed pulmonary interstitial and intra-alveolar cholesterol granulomas
      (PICG). Since treatment with steroids and immunosuppressive drugs did not prevent
      progression of lung fibrosis, an experimental treatment with a tumor necrosis
      factor alpha (TNF alpha) antagonist etanercept was started. Although development
      of chronic changes in the lung parenchyma could not be prevented, this treatment
      brought considerable relief and markedly improved the child's physical capacity.
      By ruling out other causes for development of PICG, we concluded that the primary
      disease had caused the development of cholesterol granulomata by macrophage
      activation. We suggest, therefore, that a trial with etanercept in children with
      otherwise therapy-resistant CJA should be considered, especially if pulmonary
      complications have developed.

PMID- 11596166
TI  - Noninvasive mechanical ventilation and corrective surgery for treatment of a
      child with severe kyphoscoliosis.
AB  - We report on an 11-year-old boy with severe kyphoscoliosis and respiratory
      failure. Noninvasive mechanical ventilation by nasal mask and hospitalization
      resulted in improved pulmonary function, thus facilitating corrective surgery for
      kyphoscoliosis. Following surgery, the patient remained on mechanical ventilation
      at home. Clinical and pulmonary function stabilized after discharge, as noted on
      a 1-month follow-up visit.

PMID- 11596167
TI  - Acute respiratory distress syndrome due to cyanotic spell in an infant with
      tetralogy of Fallot.
AB  - Acute respiratory distress syndrome (ARDS) is characterized by fulminant
      respiratory failure due to noncardiac pulmonary edema. This can be triggered by a
      heterogeneous group of diseases. We report an unusual case of an infant who
      developed severe ARDS in association with a severe cyanotic attack due to
      tetralogy of Fallot.

PMID- 11596168
TI  - Early administration of inhaled nitric oxide to children with acute respiratory
      distress syndrome and its effects on oxygenation and ventilator settings:
      prospective preliminary report of ten patients.
AB  - AIM: To establish a protocol for the early introduction of inhaled nitric oxide
      (iNO) therapy in children with acute respiratory distress syndrome (ARDS) and to
      assess its acute and sustained effects on oxygenation and ventilator settings.
      PATIENTS AND METHODS: Ten children with ARDS, aged 1 to 132 months (median, 11
      months), with arterial saturation of oxygen <88% while receiving a fraction of
      inspired oxygen (FiO2) >or=0.6 and a positive end-expiratory pressure of >or=10
      cm H2O were included in the study. The acute response to iNO was assessed in a 4
      hour dose-response test, and positive response was defined as an increase in the
      PaO2/FiO2 ratio of 10 mm Hg above baseline values. Conventional therapy was not
      changed during the test. In the following days, patients who had shown positive
      response continued to receive the lowest iNO dose. Hemodynamics, PaO2/FiO2,
      oxygenation index, gas exchange, and methemoglobin levels were obtained when
      needed. Inhaled nitric oxide withdrawal followed predetermined rules. RESULTS: At
      the end of the 4-hour test, all the children showed significant improvement in
      the PaO2/FiO2 ratio (63.6%) and the oxygenation index (44.9%) compared with the
      baseline values. Prolonged treatment was associated with improvement in
      oxygenation, so that FiO2 and peak inspiratory pressure could be quickly and
      significantly reduced. No toxicity from methemoglobin or nitrogen dioxide was
      observed. CONCLUSION: Administration of iNO to children is safe. iNO causes rapid
      and sustained improvement in oxygenation without adverse effects. Ventilator
      settings can safely be reduced during iNO treatment.

PMID- 11596169
TI  - Intermediate rehabilitation outcome in below-knee amputations: descriptive study
      comparing war-related with other causes of amputation.
AB  - AIM: To asses the intermediate rehabilitation outcome of patients with war
      related below-knee amputations and compare it with the patients with other causes
      of amputation. METHOD: The study comprised 74 patients with below-knee stumps
      admitted for rehabilitation at the Department of Physical Therapy and
      Rehabilitation, Split University Hospital, Croatia, in 1994. They were fitted
      with a preliminary prosthesis, a donation from the Finish Red Cross. The
      rehabilitation was performed by a professional team and included regular
      bandaging of the stump, exercises to prevent knee and hip joint contracture,
      general fitness exercises, standing-up, falling and walking exercises, and
      electrostimulation of the thigh muscles. The time to reach each rehabilitation
      phase (walking with 2 crutches, walking with 1 crutch, walking with no crutches)
      was measured. The satisfaction of the patients with the prosthesis was also
      assessed at the end of rehabilitation. RESULTS: Among 74 patients with below knee
      amputation, war trauma was the cause for amputation in 31 patients, and in 6 of
      them the amputations were bilateral. Patients with war-related below-knee
      amputations were younger than the patients with amputations related to vascular
      disease, including diabetes. The rehabilitation time was significantly shorter in
      patients with war-related amputations (61.1+/-11.4 days to walking with no
      crutches) compared with patients with vascular disease-related amputations
      (80.9+/-8.1 days; p<0.001). The satisfaction with the prosthesis was more
      variable in patients with war-related amputations than in other patients.
      CONCLUSION: Early physical rehabilitation and replacement of the lost extremity
      with a preliminary prosthesis is an optimal intervention in below-knee
      amputations due to war-injury. Special attention should be paid to the
      psychological support to these patients during rehabilitation therapy.

PMID- 11596170
TI  - Reconstruction of chronic collateral ligament injuries to fingers by use of
      suture anchors.
AB  - AIM: To evaluate the effectiveness of suture anchors in the reconstruction of
      chronic collateral ligaments of fingers. METHODS: We treated 8 patients, 6 with
      chronic instability of the collateral ligament of the thumb and 2 with the
      instability of the fifth finger, using the Statak suture anchor. A stable joint
      was achieved in each case, with no recurrent instability or pain within a mean of
      14 months of the follow up. RESULTS: Postoperatively, each patient returned to
      his or her original job, their daily activities, and sports. There was no
      significant difference on manual stress testing measurements between operated and
      uninjured fingers. Mean pinch strength and range of motion were 90% (range, 78
      104%) and 94% (range, 70-100%), respectively, compared to uninjured fingers.
      CONCLUSION: Suture anchor technique can be recommended as a simple and effective
      method of repairing the collateral ligament of fingers.

PMID- 11596171
TI  - Stressor characteristics and post-traumatic stress disorder symptom dimensions in
      war victims.
AB  - AIM: To evaluate how the type of trauma is related to specific symptom patterns
      in patients with post-traumatic stress disorder (PTSD) according to the
      Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV)
      criteria. METHODS: A total of 136 PTSD patients exposed to war-related traumatic
      experiences were divided in four groups: 79 veterans, 18 former prisoners (who
      witnessed or were subject to torture or frequent assaults), 15 victims of rape,
      and 24 refugees from Bosnia and Herzegovina. Each group was homogenous in regard
      to traumatic experiences. RESULTS: Significant inter-group differences were found
      in symptoms listed in the DSM-IV criteria, and under criteria C (avoidance) and D
      (arousal). No such differences were observed in symptoms listed under criterion B
      (intrusive symptoms). The results indicate that stressor characteristics may play
      a role not only in the variety of symptoms exhibited, but particularly in the
      number of avoidance and arousal symptoms. Victims of rape tended to present with
      more avoidance symptoms and fewer hyperarousal symptoms, whereas former prisoners
      and veterans tended to report more hyperarousal symptoms. Rape victims and former
      prisoners also reported more symptoms than the other groups. CONCLUSION: There is
      a strong indication that stressor characteristics influence the variety and
      number of exhibited intrusive, avoidance, and arousal symptoms. More research is
      needed to precisely define individual symptom dimensions possibly relating to
      particular stressor characteristics. Additional studies are needed to determine
      whether PTSD, as it is currently defined in the DSM-IV, is really a homogenous
      diagnostic category.

PMID- 11596172
TI  - Changes of cytolytic cells and perforin expression in patients with posttraumatic
      stress disorder.
AB  - AIM: To define phenotypic characteristics of cytotoxic T lymphocytes (CTL) and
      natural killer cells (NK) in peripheral blood, frequency of somatic symptoms, and
      level of anxiety and depression in 25 patients clinically diagnosed with chronic
      post-traumatic stress disorder (PTSD). METHODS: Patients were divided into two
      sub-groups according to the stressor: 18 PTSD patients with the battlefield
      experience and 7 PTSD patients with battlefield experience who were tortured as
      the prisoners of war (POW) in Bosnian-Serbian camps. The control group consisted
      of 15 healthy volunteers matched to the patients by sex and age. We tested all
      patients using Becks depression inventory, Spielberger anxiety test, and somatic
      disturbance list, and analyzed their peripheral blood lymphocytes using flow
      cytometry with the double fluorescence staining of cell surface antigens (CD3,
      CD4, CD8, CD16, and CD56) and intracellular cytolytic molecule perforin (P), a
      mediator of cytolytic action at the molecular level. RESULTS: All PTSD patients
      showed a significant level of anxiety, depression, and numerous somatic symptoms.
      The only significant difference between PTSD patients with and without POW
      experience was in the anxiety level (median, 71; range 61-79; vs median, 65;
      range, 49-77). PTSD patients with POW experience had significantly higher levels
      of CD16+ cells (median, 37%; range, 16-55%) than those without it (median, 12%;
      range, 5-37%). Double labeling for intracellular P antigen and cell surface
      antigens showed the highest levels of CD16+P+ (median, 33%; range, 15-40%; vs
      median, 10%; range, 3-29%) and CD56+P+ (median, 21%; range, 11-40%; vs median 8%;
      range, 1-30%) cells in PTSD-POW patients. CONCLUSION: Chronic PTSD patients who
      survived concentration camps show the most numerous alterations in PBL phenotype,
      the highest number of perforin-containing cells, and a significantly higher level
      of anxiety.

PMID- 11596173
TI  - Medical rehabilitation in Croatia impact of the 1991-1995 war: past problems,
      present state, future concerns.
AB  - AIM: To assess whether the 1991-1995 war has stimulated development of the
      medical rehabilitation system in Croatia. METHODS: Review of documents pertaining
      to the system, study of clinical reports describing rehabilitation activities as
      published in the Croatian medical literature, study of data obtained and their
      consideration in terms of effectiveness and quality of rehabilitation care, and
      comparison of data from 1991 with those from 1995. RESULTS: There has been no
      significant change in the number of rehabilitation facilities, beds, and
      rehabilitation professionals. However, elements of structure and process of
      rehabilitation care have improved in respect of 1) education and composition of
      rehabilitation professionals, 2) availability of specialized facilities for
      rehabilitation of patients with complex impairments (traumatic brain and spinal
      cord injuries), 3) interdisciplinary team approach, 4) use of functional status
      measurements, and 5) laying the foundations for community-based rehabilitation in
      the country. CONCLUSION: The 1991-1995 war has stimulated the development of
      medical rehabilitation system in Croatia. Other factors may have played a
      complementary role, too. This proves that medical rehabilitation is a field that
      develops in association with war.

PMID- 11596174
TI  - Regional occupational health service - an assessment.
AB  - AIM: To present, partially in quantitative terms, the basic characteristics of a
      regional occupational health service in southern Israel. METHOD: Records of the
      annual activities of the regional occupational health service were analyzed over
      a period of about 10 years. RESULTS: Overall there were about 25,000 contacts per
      year, such that about 15,000-16,000 different individuals were examined each year
      (out of a population of about 150,000 workers). About 45% of the examinations
      performed were surveillance (statutory), 38% fitness-to-work, and 15% pre
      employment examinations. These proportions were quite stable over the whole study
      period, even though services are provided to hundreds of work-sites of markedly
      different sizes, exposures, and technological development. As expected, the type
      and rate of abnormal findings differ significantly among the 3 categories: 7% for
      pre-employment examinations, 18% for surveillance, and 53% for fitness-to- work
      examinations. CONCLUSION: In order to provide adequate occupational health
      services to a large, non-uniform population of workers, a clear understanding of
      the "occupational map" of the region is needed. A good insight into the
      characteristics, aims, and scope of the 3 main categories of examinations used in
      occupational health could assist in forecasting, planning, and providing adequate
      regional occupational health service.

PMID- 11596175
TI  - Left Bochdalek hernia with delayed presentation: report of two cases.
AB  - Left Bochdalek hernia is a serious and complex condition with high mortality. In
      most cases, it presents in the neonatal period and is seldom found later in life
      when symptomatology, usually after an asymptomatic period, is quite different and
      the prognosis excellent. The embryological development of left Bochdalek hernia
      suggests the presence of abdominal content in the left pleural cavity before
      birth. The type of clinical presentation and the prognosis depend on the time of
      visceral herniation. This study presents two cases of left Bochdalek hernia with
      delayed presentation. In both cases, after surgical reposition of the hernia, a
      small congenital diaphragmatic defect was found hidden between the rims of
      diaphragm. This indicates the possibility for the abdominal content to enter the
      left pleural cavity at the time of presentation.

PMID- 11596176
TI  - Meningitis and endocarditis caused by group B streptococcus in a human
      immunodeficiency virus (HIV) infected patient.
AB  - We present a case of meningitis and endocarditis caused by Streptococcus
      agalactiae (group B streptococcus) in an adult patient with human
      immunodeficiency virus (HIV) infection. To our knowledge, only four other cases
      of meningitis, none of which had concomitant endocarditis, have been reported so
      far. A 45-year-old homosexual patient presented with fever, confusion, and signs
      of meningeal irritation. Streptococcus agalactiae was cultured from the blood,
      urine, and cerebrospinal fluid (CSF). Diagnosis of meningitis caused by
      streptococcus agalactiae was made. On day 35, a heart murmur was noticed, and
      patient developed cardiac decompensation. Echocardiography revealed vegetations
      on the mitral and aortic valve. After nine weeks of antibiotic treatment, the
      patient was discharged from the hospital in good general condition, with improved
      CSF and echocardiographic findings.

PMID- 11596177
TI  - Death due to accidentally self-inflicted gunshot wound.
AB  - A 37-year-old man, with the entrance gunshot wound on the front of the right leg
      several cm above the knee, was found dead at home in his bed. No other lesions
      were observed except a contusion ring around the wound that spread downward and
      to the right. On autopsy, the wound path was followed upward from the entrance
      wound (0.7 cm in diameter). The bullet went through the medial aspect of the
      quadriceps and adductor muscles and continued upward, adjacently to the internal
      iliac artery, perforating the pelvic floor and the median lobe of the prostate.
      It passed by the left kidney, injuring its fatty capsule, then went through the
      mesentery near the left segment of the transverse and descending colon, and
      entered the thoracic cavity through the diaphragm, injuring the posterior wall of
      the pericardium and the posterior wall of the left ventricle at the level of the
      first left rib. The bullet was found in the apex of the left lung. Death was
      caused by cardiac tamponade.

PMID- 11596178
TI  - Unusual stab wound of the temporal region.
AB  - We report the case of an unusual penetrating injury of the temporal region of the
      head caused by knife. A long kitchen knife was protruding from the upper
      auricular area of the left temporal region of victims head. It cut through the
      posterosuperior part of the left auricula and remained fixed to the postauricular
      region. Brain computorized tomography (CT) scan revealed that the knife had
      reached deep into the petrous part of the temporal bone, and was directed toward
      the sulcus of the sigmoid sinus. There were no signs of intracranial bleeding. An
      otorhinolaryngologist and a neurosurgeon removed the knife in operating room,
      with the patient in general anesthesia. The audiogram obtained after 7 days of
      hospitalization showed left conductive hearing loss of 40 dB at frequencies up to
      2 kHz, and of 90 dB above 2 kHz, probably due to hemotympanum caused by the
      operation. Control examinations performed 14 days and one month after discharge
      confirmed the patients complete recovery and no significant defects in his
      hearing or balance. We suggest multidisciplinary teamwork as a proper approach in
      the treatment of such injuries.

PMID- 11596179
TI  - He knows joy in all that he does: on the occasion of Jan Klein's 65th birthday.

PMID- 11596180
TI  - Our scars.

PMID- 11596181
TI  - Improving the quality of care - the case of anticoagulant therapy.

PMID- 11596182
TI  - [The immunomodulatory effect of Achyranthes bidentata polysaccharides].
AB  - Achyranthes bidentata polysaccharides(ABPS) was extracted from the root of
      Achyranthes bidentata Blume with molecular weight of 1400. It composed of
      fructose and glucose residues. The molar ratio was 8.7:1.0. It was a water
      soluble neutral polysaccharide of white powder in purity of 99.9%. The effect of
      ABPS 0.625 x 10(2)-2.00 x 10(3) mg.L-1 on lymphocyte proliferation to Con A on
      splenocytes from aged mice was evaluated to be about 1.11-3.26 folds in vitro.
      ABPS 1.00 x 10(3) mg.L-1 was shown to increase IL-2 production in Con A
      stimulated aged mouse splenocytes from 6.7 +/- 1.0 u.ml-1 to 19.3 +/- 5.7 u.ml-1
      in vitro. Sandwish-ELISA was used for the determination of TNF-alpha, TNF-beta
      and sIL-2R in cell suspension. The spectrophotometry with Griess reagent was used
      for the determination of NO in cell suspension. A method was developed for the
      determination of NOS activity in biological sample by HPLC. ABPS 50, 100 mg.kg-1
      i.p. was found to markedly promote TNF-beta and NO release, but decrease sIL-2R
      production from Con A-stimulated aged rat splenocytes, the activity of NOS in
      those cells was increased. ABPS 100 mg.kg-1 i.p. elevated serum TNF-alpha and NO
      contents and the NOS activity induced by LPS 0.3 mg.kg-1 i.p. in aged rats. ABPS
      50-800 mg.L-1 elevated TNF-alpha and NO production from PM phi and increased the
      NOS activity in PM phi in vitro, but showed no significant influence on TNF
      alpha, NO release and on NOS activity induced by LPS 10 mg.L-1 for PM phi from
      aged rats. ABPS 100 mg.kg-1 i.p. elicited TNF-alpha, NO production and NOS
      activity for PM phi from aged rats, ABPS 100 mg.kg-1 i.p. showed a synergetic
      action with LPS 10 mg.L-1. When rats were treated with ABPS 50-800 mg.L-1 i.p.,
      there was no significant difference on NO production on, and NOS activity in the
      cerebral cortex between those isolated from aged rats and those isolated from
      young rats. These results indicate that ABPS may prime and trigger M phi and has
      restorative effects on the deficiency of the immune system associated with aging
      in mice and rats.

PMID- 11596183
TI  - [The anti-anaphylactic action of potassium channel openers and its mechanism].
AB  - The anti-anaphylactic action of potassium channel openers was studied and
      reported in this paper. Minoxidil(Min) was shown to inhibit passive cutaneous
      anaphylaxis in rats. Diazoxide (Dia) and Min were found to inhibit antigen
      induced guinea-pig ileum smooth muscle contraction in vitro. Min was shown to
      antagonize 5-HT-induced capillary permeability in rat skin. Dia was demonstrated
      to inhibit histamine release from rat peritoneal mast cells induced by A23187 and
      compound 48/80, but it failed to antagonize guinea-pig ileum smooth muscle
      contraction induced by histamine in vitro. These results provide evidence that
      potassium channel openers may be a new group of inhibitors of histamine release
      and indicate that the mechanism of its anti-anaphylactic action may be related to
      its potassium channel opening effect. As a result of this effect, Ca2+ influx to
      the mast cells decreases and Ca2+ release from calcium storage was inhibited,
      thus inhibiting histamine release.

PMID- 11596184
TI  - [Production and secretion of interleukin 6 from stimulated peritoneal macrophages
      of the mouse].
AB  - In this paper, a bioassay method involving the interleukin 6 dependent murine
      hybridoma B9 cell line was used to detect the level of released and cell
      associated interleukin 6 in resident peritoneal macrophages from the mouse. The
      phorbol ester, phorbol 12-myristate 13-acetate (PMA), the calcium ionophores
      A23187, the chemotactic peptide fMLP and lipopolysaccharide(LPS) were introduced
      in these experiments as stimulators. PMA, A23187 and fMLP were shown to induce a
      dose-dependent increase of both released and cell-associated interleukin 6,
      whereas, LPS caused increase of interleukin 6 activity in supernatants of
      cultured peritoneal macrophages of the mouse. The effects of PMA and A23187
      suggested that the pathway of PKC and calcium is involved in the production and
      secretion of interleukin 6. The effects of fMLP and LPS provided evidence that
      they participated in the process of inflammation. The difference between LPS and
      the other three stimulators in cell-associated interleukin 6 activity might
      suggest a different mechanism of actions of generation of interleukin 6.

PMID- 11596185
TI  - [Synthesis of epipodophyllotoxin carboxylates and antitumor activity in vitro].
AB  - A series of epipodophyllotoxin carboxylates were prepared from podophyllotoxin by
      reacting with organic acids under the catalysis of BF3.Et2O. All these products
      were characterized through IR, 1HNMR, MS and elemental analysis. These compounds
      showed significant antitumor activities against mouse leukemia P388 and human
      stomach cancer SGC-7901 in pharmacological tests in vitro.

PMID- 11596186
TI  - [Synthesis and antifungal activities of 1-(2-[(substituted-phenyl) methyl]thio)-2
      (2,4-difluorophenyl)ethyl-1H-1,2,4-triazoles].
AB  - Twenty-one 1-[2-[[(substituted-phenyl) methyl] thio]-2-(2, 4-difluorophenyl)
      ethyl]-1H-1,2,4-triazoles were synthesized and 19 compounds are reported for the
      first time. Results of biological tests in vitro showed that the antifungal
      activities of all title compounds were better than or comparable to the
      activities of fluconazole. The antifungal activities of compounds 1-7 and 11-17
      were better than or comparable to the activities of sulconazole. Compounds 1, 2
      and 5 were 512 times more active than sulconazole against epidermophyton
      floccosum; compound 5 was 32 times more active against Candida albicans, compound
      2 was 32 times more active against Sporotrichum schenckii; compounds 2 and 14
      were shown to be 64 and 32 times more active against Cryptococcus neoformans;
      compounds 1 and 5 were 16 times more active against Aspergillus fumigatus.

PMID- 11596187
TI  - [Chemical investigation of genus Hedyotis. II. Isolation and identification of
      iridoids from Hedyotis chrysotricha].
AB  - Many species of genus Hedyotis (Rubiaceae) were used as folk medicine for
      treatment of cold, inflammation, cancer and etc. in China. The alcoholic extract
      of the whole plant of H. chrysotricha showed good hepatoprotective effects. From
      the alcoholic extract ten iridoids were isolated and their structures were
      elucidated as: asperuloside (1), scandoside methyl ester (2), asperulosidic acid
      (3), deacetyl asperulosidic acid (4), loganin (5), deacetyl asperuloside (6),
      acetyl scandoside methyl ester (7), 6 beta-hydroxy-genipin (8) and two new
      compounds named hedyoside (9) and 6'-acetylasperuloside (10), by means of
      chemical and spectral methods.

PMID- 11596188
TI  - [Studies on chemical structures of two iso-acetogenins from Annona reticulata].
AB  - Two annonaceous acetogenins: squamone (1) and isoannonareticin (2) have been
      isolated from the seeds of Annona reticulata L. (Annonaceae). 1 and 2 were shown
      to be mixtures of 2-epimers by the successful separation of their acetates with
      preparative TLC, giving: 2,4-cis-squamone diacetate (1a-1), 2,4-trans-squamone
      diacetate (1a-2), 2,4-cis-isoannonareticin diacetate (2a-1) and 2,4-trans
      isoannonareticin diacetate (2a-2). The 2,4-cis-squamone (1-1) and 2,4-trans
      isoannonareticin (2-1) are new annonaceous acetogenins. Their structures and
      relative stereochemistry were elucidated on the basis of spectral analysis (1H-1H
      COSY and NOE).

PMID- 11596189
TI  - [Determination of acetylcholine by high performance liquid chromatography, enzyme
      loaded postcolumn, and electrochemical detector].
AB  - A rapid and simple method using a combination of high performance liquid
      chromatography (HPLC), an immobilized enzyme column, with electrochemical
      detection (ECD) is described for the assay of acetylcholine (ACh) and choline
      (Ch) in mouse brain. Perchloric acid extracts of small brain tissue were injected
      onto the HPLC system with no preclean-up procedure Detection limits for both
      compounds were 1 pmol. The present method has been successfully applied to the
      measurement of ACh in discrete brain areas of the mouse.

PMID- 11596190
TI  - [Distinguishing CYP2D6 homozygous and heterozygous extensive metabolizers by
      dextromethorphan phenotyping].
AB  - A more sensitive procedure was developed to phenotype cytochrome P450 2D6
      metabolism by a less toxic probe drug--dextromethorphan. The sensitivity of the
      determination of dextromethorphan in urine samples was up to 1 ng.ml-1. This
      method was employed to phenotype three groups of subjects. The results showed
      that there was a difference between extensive metabolizers which were genotyped
      as homozygotes and heterozygotes. Although the difference was not as big as the
      difference with poor metabolizers which were genotyped as homozygous mutants. It
      suggests that "gene copy" is a true factor in the expression of CYP2D6 genes.

PMID- 11596191
TI  - [Analysis of paeonol in Paeonia suffruticosa Andr. and its patent preparations by
      supercritical fluid extraction and capillary gas chromatography].
AB  - A supercritical fluid extraction (SFE) method was developed for the extraction of
      paeonol in Paeonia suffruticosa Andr. and its patent preparations. A systematic
      method was used to optimize five variables (temperature, pressure, modifier
      concentration, static extracting time and CO2 dynamic extracting volume) of SFE.
      Sample extracts were analyzed by wide-bore capillary gas chromatography (CGC).
      The method showed good linearity (gamma = 0.9999) in the range of 0.1-1.6 mg.ml-1
      of paeonol. The average recovery was 97.8% with RSD = 2.35% (n = 3) for Paeonia
      suffruticosa andr., 100.3% with RSD = 1.89% (n = 3) for its patent preparations.

PMID- 11596192
TI  - [Degradation of liquid preparations of four fluoroquinolones by factorial
      experiment. ].
AB  - The effects of light, pH and ionic strength on the degradation of four
      fluoroquinolones (norfloxacin, NFX; ofloxacin, OFX; ciprofloxacin, CPX;
      lomefloxacin, LEMX) solutions were studied. Using 2(3) factorial experiment and F
      test, it was confirmed that the degradation of NFX, OFX, CPX and LEMX was
      affected very markedly by light, but almost not affected by the ionic strength of
      the solution. The degradation of OFX and CPX was affected very markedly by pH,
      but the degradation of NFX and LEMX was almost not affected by pH. The
      degradation of OFX and CPX was affected very markedly by the combined action of
      light and pH, but the degradation of NFX and LEMX was almost not affected by the
      combined action of light and pH.

PMID- 11596193
TI  - [Study on the degradation kinetics of spiramycin in acid and alkaline solutions].
AB  - Physical and chemical characteristics of spiramycin (SPM) were reviewed in this
      paper. The degradation rule and kinetics of SPM in acid and alkaline solutions
      were studied, and the kinetic parameters were calculated. The experimental
      results showed that the stable range of SPM in water is at pH 4.0~10.0
      Degradation occurred seriously at pH<4.0 and pH> 10.0, especially at pH< 2.8 and
      pH> 12.8. For this reason, the yield of SPM is greatly affected. The solubility
      in water was also studied by using reference data. The thermodynamical parameters
      were calculated. The results showed that the solution of SPM in water is
      exothermic. The solubility decreases as temperature rises.

PMID- 11596194
TI  - [Synthesis and biological activity of substance P analogs].
AB  - Substance P (SP) and its three analogs were synthesized through solid-phase
      procedure. The fully-protected peptide-resin was cleaved with anhydrous HF.--SH
      of Cys in [Cys5,9] SP(4-11) was protected with Acm, then deprotected through
      Iodine oxidation method, the disulfide bridge cyclization was formed
      subsequently. The crude product was purified on C18 RP-HPLC. The results of
      guinea-pig isolated ileum test (GPI) showed that the potency of the analogs was
      as follows: [AcGln5, Pro9] SP(5-11) > SP > SP(4-11) > [Cys5,9] SP(4-11). They
      induced GPI to contract very fast and showed the characteristics of tachykinin.
      On the writing test in mice, the results showed: [Cys5,9] SP(4-11) > SP > SP(4
      11) > [AcGln5, Pro9] SP(5-11). The biological tests showed that the SP analogs
      have some extent of selectivity.

PMID- 11596196
TI  - [Mimetic principle of molecular drug design].

PMID- 11596195
TI  - [Synthesis and antifungal activity of 1-(1H-1,2,4-triazole-1-yl)-2-(2,4
      difluorophenyl)-3-substituted-2-propanols].
AB  - Twenty-three 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2
      propanols were synthesized and evaluated for antifungal activities in vitro. The
      synthetic methods of the intermediates are also reported. The compounds belong to
      two kinds: sulfones and sulfides. All of the compounds are new. The results of
      preliminary antifungal test showed that most of the sulfide derivatives exhibited
      potent activities against six kinds of common pathogenic fungi such as
      Microsporum lanosum, Cryptococcus neoformans, Candida albicans, Aspergillus
      fumigatus, Cladosporium carrionii, and Saccharomyces torulopsis in vitro.
      Compounds IVe, f,i,j showed equal or more potent activities when compared with
      ketoconazole and were markedly superior to fluconazole. The sulfone derivatives
      showed lower antifungal activity.

PMID- 11596197
TI  - [Effect of gossypol in combination with misoprostol on termination of early
      pregnancy in rats and mice].
AB  - Treatment of mice with misoprostol alone at doses ranging from 200 to 6400
      micrograms.kg-1, qid on day 6-8 or bid on day 9 of gestation, the rate of
      effective early pregnancy interruption were low and showed no dose effect
      relation. When giving misoprostol 200-6400 micrograms.kg-1 bid on day 9 of
      gestation following administration of gossypol 50 mg.kg-1 qid on day 6-8, the
      rate of abortion increased as the dose of misoprostol increased, and the ED50 of
      misoprostol was 397.8 micrograms.kg-1. The ED50 of gossypol given orally on day 6
      8 of gestation was 69.4 mg.kg-1. However, when gosyypol was given in combination
      with misoprostol 400, 800 or 1600 micrograms.kg-1 on day 9 bid, the ED50 of
      gossypol decreased to 63.2, 48.6 or 34.9 mg.kg-1, respectively. The results
      suggest that combination of gossypol and misoprostol showed synergistic effect on
      termination of early pregnancy in mice. Misoprostol obviously strengthened the
      uterine contraction of rats both in early pregnancy and estrus in vitro. The
      contraceptive intensity of contraction was increased as the dose of misoprostol
      increased from 10(-9), 10(-8) to 10(-7) mol.L-1, and the estrus group was higher
      than the early pregnancy group (P < 0.01). Gossypol(10(-5)-10(-6) mol.L-1) showed
      no effect on the uterine activity in rats, but the sensitivity of the uterus of
      the early pregnant rats to misoprosrol was found to be significantly increased by
      treatment with gossypol on day 6-8 of gestation (P < 0.01). Degeneration of the
      decidual was observed under light microscopy when gossypol 80 mg.kg-1.d-1, or
      misoprostol 800 micrograms.kg-1.d-1, or gossypol 40 mg.kg-1.d-1 combined with
      misoprostol 400 micrograms.kg-1.d-1 was given orally to rats on day 6-8 of
      pregnancy. The degeneration of cells was more remarkable when both drugs were
      given in combination. The assay of immunoreactivity for PR demonstrated that the
      distribution and content of PR in uterine decidua had no difference between the
      control group and the treated groups.

PMID- 11596198
TI  - [Effect of oxyphenamone, a new inodilator, on isolated cardiac muscles and
      arteries].
AB  - The cardiotonic and vasodilating effects of oxyphenamone were studied in
      preparations of rat Langendorff's heart, isolated cardiac muscles of guinea pigs
      and isolated arteries of dogs. In the preparations of rat Langendorff's heart,
      infusion of oxyphenamone at 0.1 and 1.0 mumol.L-1 increased myocardial
      contractility and coronary blood flow moderately and decreased heart rate
      slightly. Oxyphenamone (1-100 mumol.L-1) increased the contractile force of
      papillary muscle (PM) and left atrium (LA) of guinea pigs dose-dependently. The
      positive inotropic effect of oxyphenamone (the ED50 was found to be 18.35 mumol.L
      1 in PM and 9.17 mumol.L-1 in LA) was close to that of milrinone, an inhibitor of
      phosphodiesterase(the ED50 was shown to be 6.23 mumol.L-1 in PM and 4.59 mumol.L
      1 in LA). The difference between these two agents is that oxyphenamone decreased
      the spontaneous pulse rate of right atrium, while milrinone increased it. The
      vasoconstrictions of dog coronary, basilar and mesenteric arteries induced by
      KCl, 5-HT and CaCl2 were antagonized non-competitively by oxyphenamone at 1 and
      50 mumol.L-1, suggesting that oxyphenamone has a relaxant effect on vascular
      smooth muscles.

PMID- 11596199
TI  - [Determination of caffeine metabolite for the evaluation of N-acetyltransferase,
      CYP1A2 and xanthine oxidase activities].
AB  - Caffeine was used as a metabolic probe to measure, in 120 healthy volunteers, the
      activities of three enzymes, deduced to be N-acetyltransferase(NAT2), CYP1A2 and
      xanthine oxidase (XO). The caffeine metabolites of 5-acetylamino-6-formylamino-3
      methyluracil (AFMU), 1-methylxanthine(1X), 1-methyluric acid(1U), 1, 7
      dimethylxanthine(17X), and 1, 7-dimethyluric acid(17U) in urine were determined
      with HPLC after 4-5 hours of caffeine drink. The ratios of AFMU/1X or AFMU/(AFMU
      + 1X + 1U), (AFMU + 1X + 1U)/17X or (AFMU + 1X + 1U)/17U, and 1U/1X or 1U/(1X +
      1U) were used as the index of NAT2, CYP1A2, and XO activities respectively.
      Frequency distribution analysis of the metabolic ratios of NAT2 indicated two
      distinct group with 20 slow acetylators and 100 rapid acetylators. Similar CYP1A2
      activity was found in Chinese compared with European volunteers. Frequency
      analysis of CYP1A2 indicated the log normal distribution in 120 Chinese. The
      CYP1A2 index was much higher in smokers than that in nonsmokers. But no obvious
      difference was observed between young and old volunteers. The XO index also
      showed log normal distribution and has the similar value compared with European
      volunteers. The concentration variations of 1X and 1U in young volunteers were
      much lower than that in old volunteers.

PMID- 11596200
TI  - [8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate(TMB-8) reduced the
      elevation of [Ca2+]i induced by BHQ, NE and KCl in cultured single smooth muscle
      cells of the calf basilar artery].
AB  - The effect of 8-(N, N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate (TMB-8) on
      the elevation of [Ca2+]i induced by 2, 5-di (tert-butyl)-1, 4-benzohydroquinone
      (BHQ), norepinephrine (NE), KCl in cultured single smooth muscle cells of the
      calf basilar artery was studied by a system of measurement of AR-CM-MIC, using
      Fura-2/AM as a fluoresent indicator. In the presence of extracellular Ca2+ 1.3
      mmol.L-1, the resting [Ca2+]i was not changed by TMB-8 (10, 30 and 100 mumol.L
      1), but the elevation of [Ca2+]i induced by BHQ, NE and KCl were reduced by TMB-8
      (30 mumol.L-1) significantly. In Ca2+ free Hank's solution containing EGTA 0.1
      mmol.L-1, the resting [Ca2+]i was markedly reduced by TMB-8 (10, 30 and 100
      mumol.L-1), and the increase of [Ca2+]i evoked by BHQ and NE was blocked
      completely by TMB-8 (30 mumol.L-1). The result suggested that TMB-8 inhibited the
      Ca2+ release from intracellular stores or increased the up-take of Ca2+ into
      sarcoplasmic reticulum and the inhibition of Ca(2+)-influx from extracellular
      site may be an indirect machanism.

PMID- 11596201
TI  - [Crystal and molecular structure of the antimalarial agent alpha
      (dibutylaminomethyl)-2, 7-dichloro-9-(p-chlorobenzylidene)-4-
      fluorenemethanol(benflumetol)].
AB  - The three-dimensional crystal and molecular structure of benflumetol(I), alpha
      (dibutylaminomethyl)-2, 7-dichloro-9-(p-chlorobenzylidene)-4-fluorenemethanol,
      was determined by X-ray crystallography and compared with the crystal structures
      of the cinchona alkaloids. The aromatic rings of fluorene-phenyl system of
      benflumetol are twisted from each other by 52.8 degrees. The torsion angle of N-C
      C-O of benflumetol is 47.6 degrees. The intramolecular aliphatic N-O distance in
      benflumetol is 2.709A, which is close to the N-O distance found in antimalarial
      cinchona alkaloids. Benflumetol contains an intramolecular hydrogen bond between
      the aliphatic nitrogen and oxygen atoms, no intermolecular hydrogen bond was
      found, which is different from the known amino alcohol antimalarials.

PMID- 11596202
TI  - [Studies on retinoids. IV. Design, synthesis and structure-activity relationships
      of di-t-butylphenyl compounds].
AB  - Retinoic acid and its analogues play important roles in modulating cell growth,
      differentiation, immunity and apoptosis. Clinically they are used for cancer
      chemoprevention and chemotherapy. Based upon the moiety of 3,5-di-t-butyl-4
      hydroxy phenyl ring, a series of substituted aromatic amide, ester and chalcones
      were designed and synthesized, which mimic the molecular shape, size, and spacial
      disposition of functional groups of retinoic acid. The general structure is as
      follows: [formula: see text] where R stands for hydrogen atom or methyl group, Y
      is the linkage -CONH-, -NHCO-, -COO-, -COCH = CH-, or a member of a heterocycle,
      X represents various substituents at different positions. The SAR indicates that
      the presence of hydrophobic group(s) at one end of the molecule, and a carboxyl
      group at the other end, and a conjugative system of molecule are necessary and
      full prerequisite for exhibiting activity. Loss of any one factor of them will
      abolish the activity. Being obligatory for anti-oxidative effect, the phenolic
      hydroxy group does not convey biological activity, because after methylation of
      the hydroxy group the compound increases the differentiation-inducing activity
      and loses the anti-oxidative effect, indicating that there is no correlation
      between the two activities. With a stable conformation of two phenyl rings with
      cis-conformation N-methylated acyl amide (No. 30) features in bent shape of the
      molecule, instead of an extended conformer, which is taken by the non-N
      methylated partner and all-trans retinoic acid. A bent conformer of No. 30
      accounts for the inactivity. In this paper compounds No. 4f, 4g, 5a, 7, 13, 32,
      37, and 38 exhibited significant activity among them 4-[3-(3, 5-di-t-4
      methoxyphenyl)-3-oxo-1-propenyl] benzoic acid (No. 38) showed high activity
      comparable to that of retinoic acid. The pharmacological action of No. 38 is
      under investigation.

PMID- 11596203
TI  - [Studies on pyridonecarboxylic acids as antibacterial agents.  XII. Synthesis and
      antibacterial activity of 6-chloro-1-cyclopropyl-7-(1-piperazinyl)-1, 4-dihydro-4
      oxo-quinoline-3-carboxylic acid and analogues].
AB  - Sixteen pyridonecarboxylic acids, characterized by having a chlorine atom and a
      cyclopropyl group at the 6- and 1-position respectively, substituted amino groups
      at the 7-position, and some substituted groups (chloro, nitro, amino,
      dimethylamino) at the 8-position, were synthesized. In vitro antibacterial
      activities of these compounds were tested. The fluoroquinolones ciprofloxacin and
      norfloxacin were included for comparative purposes. The results showed that both
      11 Ca and 11 Cc were 4-8 times more active than ciprofloxacin and norfloxacin
      against S. aureus-15 in vitro, but with the same activity as ciprofloxacin
      against E. coli-22 and P. aeruginosa-29.

PMID- 11596204
TI  - [Studies on the steroidal alkaloids from Sarcococca vagans].
AB  - The root of Sarcococca vagans Stapt (Buxaceae) is well-known Chinese folk drug
      called as "Jie Gu Mu", distributed in southern of China. They are used in
      treatment of traumatic injury. Four new steroidal alkaloids, named sarcovagine A,
      B, C and D, were isolated from the root of Sarcococca vagans. Their structures
      were established on the basis of spectral evidence.

PMID- 11596205
TI  - [Solid phase extraction and high performance liquid chromatographic determination
      of enalapril in human plasma].
AB  - A reversed phase high performance liquid chromatographic method utilizing solid
      phase extraction has been described for the determination of enalapril in human
      plasma. The C18 sorbent cartridges were conditioned and plasma samples were
      applied, washed with 20 mmol.L-1 HCl (2 x 0.5 ml) and petroleum ether (boiling
      range 60-90 degrees C) subsequently; and eluted with methanol (3 x 0.5 ml). The
      eluent was evaporated to dryness, reconstituted in 100 microliters mobile phase
      and injected. Chromatographic separation was achieved on a Spherisorb C8 column
      (200 mm x 4.6 mm, 5 microns), with ethanol--water--10% H3PO4--triethylamine
      (30:70:1.5:0.1) at a flow rate of 1.0 ml.min-1. UV detection was set at 215 nm.
      The calibration ranges were 2.5-150 ng.ml-1 with regression coefficient of 0.997
      and detection limit of 1.5 ng.ml-1. The within-day RSD and between-day RSD were <
      8.73%, the recovery of method > 91.6%. This method was applied to the
      pharmacokinetic analysis of enalapril in 8 human volunteers.

PMID- 11596206
TI  - High performance liquid chromatographic determination of dextromethorphan and its
      metabolite in human urine.
AB  - A reverse-phase high-performance liquid chromatographic method was established
      for the determination of dextromethorphan (DM) and its metabolite dextrophan (DX)
      in human urine. The sample was purified by an acid-base extraction followed by
      HPLC analysis on a phenyl column. The eluate was monitored by fluorescence at 280
      nm (excitation) and 310 nm (emission). The limit of detection of DM was 0.023
      mg.L-1. The within-day and between-day RSD% of DM and DX were all lower than 5%.
      The average recovery was 104.78%.

PMID- 11596207
TI  - [Quantitative analysis of soporific sedative drugs and local anesthetic drugs
      with unidentical standard substance by GC-AED].
AB  - According to the principle of GC-AED (gas chromatography-atomic emission
      detector), the possibility of quantitative determination of samples by different
      substances as internal standard was studied. The element C was determined at
      wavelength of 496 nm. The relative response factors of 17 soporific sedative and
      local anesthetic drugs were analyzed with an internal standard of proadifen
      hydrochloride under optimized analytical conditions. Oven temp.: 45 degrees C
      (0.5 min)-35 degrees C.min-1--120 degrees C-15 degrees C.min-1--220 degrees C-5
      degrees C.min-1--250 degrees C; Cool on column injector temp: 60 degrees C-50
      degrees C.min-1--250 degrees C (0.2 min); inject volume: 1 microliter; column
      head pressure: 145 kPa. The results show that the element C(496) in identical or
      unidentical substances has similar relative response factor. The RSD is 10.21%,
      which means that a sample can be quantitatively determined by a different
      substance when the analysis condition and the selected internal standard are
      suitable. An amobarbital sample of 109.0 micrograms.ml-1 was quantitatively
      determined by using methylphenobarbitone, pramoxine, lidocaine and itself as
      internal standard. The results are 117.6, 115.6, 110.0 and 102.14 micrograms.ml
      1, respectively. They can be quantitatively determined by each other.

PMID- 11596208
TI  - [A new dynamic model of release for not-corroded drug system--revision and use of
      Fick's first law].
AB  - Based on the facts that the diffusion coefficient in original Fick's first law is
      not a strict constant but changes with concentration and that the original Fick's
      first law is only suitable for the stable diffusion with constant concentration
      gradient but many experiments have shown that the concentration gradient is a
      function of time. The authors suggest that the diffusion coefficient and the
      concentration gradient should be revised, respectively, as a concentration
      function and a time function. That is, [formula: see text] So, the Fick's first
      law is revised as [formula: see text] In the formula, dW/dt represents the rate
      of diffusion. D0 is the intrinsic diffusion coefficient that is a constant only
      concerning the temperature and the character of the substance diffused. A is the
      area of diffusion surface, alpha is the constant concerning the change of
      concentration gradient, C0 and C is, respectively, the concentration on the
      diffusion surface at time t0 and any time t. Based on this, the dynamic model of
      release on the preparations not-corroded is derived: [formula: see text] Here, k0
      is the release constant concerning D0, temperature, C0 and A. The model gave
      better results than other models in common use for simulating the release dynamic
      process and the physical meanings of the model parameters are explicit.

PMID- 11596209
TI  - [Synthesis and antimalarial activities of fluorenemethanols].
AB  - For the purpose of improving the oral antimalarial activities of the
      fluorenemethanols (reported by us in previous articles) which were less effective
      by oral than by subcutaneous administration, 24 alpha-(alkylaminomethyl)-2, 7
      dichloro-9-substituted benzylidene-4-fluorenemethanols (III) were synthesized.
      The results of preliminary screenings demonstrated that five compounds (No. 1-4,
      8) exhibited significant antimalarial activities against Plasmodium berghei NK65
      strain in mice by oral administration, at dose of 6.25 mg.kg-1.d-1 x 3 with
      suppressive rate of 100%. Further evaluation of these 5 compounds showed that 4
      of them (No. 1-4) were superior to chloroquine in parallel tests, their ED50 and
      ED90 were 1.0, 1.6; 0.6, 0.9; 0.7, 1.5 and 0.8, 1.6 mg.kg-1.d-1 x 3 respectively,
      while the ED50 and ED90 of chloroquine were 1.9 and 2.9 mg.kg-1. d-1 x 3
      respectively; one compound (No 8) was equal to chloroquine, its ED50 and ED90
      were 1.5 and 3.2 mg.kg-1.d-1 x 3 respectively. Further assessment of these 4
      compounds are in progress.

PMID- 11596210
TI  - [The structure correction of villosolside].
AB  - The crystal structure of villosolside was determined by X-ray diffraction, which
      led to some stereochemical amendment of the structure proposed in the article by
      Xu CJ et al. in Acta Pharm Sin 1985, 20:652.

PMID- 11596211
TI  - [Effect of berberine on cytosolic free calcium of rat myocardial cells in vitro].
AB  - In order to verify the inotropic effect of berberine (Ber) on myocardial tissues,
      the effect of Ber on cytosolic free calcium [Ca2+]i in cultured rat single
      myocardial cells were examined by using Fura-2/AM and AR-CM-MIC cation
      measurement system. Ber (10-400 mumol.L-1) was found to increase the resting
      [Ca2+]i and saturate at about 200 mumol.L-1. The [Ca2+]i increase was not
      depressed by atropine, phentolamine, propranolol and tetrodotoxin, but was
      inhibited by verapamil (Ver) 3 mumol.L-1 or CoCl2 10 mmol.L-1. The [Ca2+]i
      increase induced by Ber (30 mumol.L-1) added to stimulating agents as KCl, CaCl2,
      NE or Oua was stronger than that induced by stimulating agents only and Ver 3
      mumol.L-1 still showed inhibitory effects on the [Ca2+]i increase. Under Ca(2+)
      free or Ca(2+)-, K+, Na(+)-free conditions, Ber (30-200 mumol.L-1) still showed
      ascending effects on [Ca2+]i, and Ver 3 mumol.L-1 only inhibited the Ber effects
      in Ca(2+)-free condition. The results suggest that Ber might induce moderate
      [Ca2+]i increase via Ca2+ influx and intracellular Ca2+ release, and show
      positive inotropic effect.

PMID- 11596212
TI  - [Effect of TMB-8 on the increase of intracellular free Ca2+ induced by NE and BHQ
      in dissociated single rat brain cell].
AB  - The inhibitory effect and mechanism of 8-(N, N'-diethylamino) octyl 3, 4, 5
      trimethoxybenzoate hydrochloride (TMB-8) on the elevation of single intracellular
      free Ca2+ concentration ([Ca2+]i) induced by High K+, Norepinephrine(NE) and 2, 5
      Di(tert-butyl)-1, 4-benzohydroquinone (BHQ) in dissociated single rat brain cells
      were studied. The changes of [Ca2+]i were reflected by the fluorescent indicator,
      Fura-2/AM, employed. In the absence of extracellular Ca2+, Ca-free Hank's
      solution, preincubation with TMB-8 (10, 30 mumol.L-1) for 20 min significantly
      decreased the resting [Ca2+]i from 79 +/- 13 nmol.L-1 to 65 +/- 11 and 61 +/- 6
      nmol.L-1, respectively. [Ca2+]i were markedly increased by NE and BHQ and reduced
      significantly to control level by TMB-8. On the other hand, when the cells were
      incubated in Hank's solution containing Ca2+ 1.3 mmol.L-1, TMB-8(30, 100 mumol.L
      1) suppressed the increase of [Ca2+]i induced by NE (0.0001-0.1 mumol.L-1). TMB-8
      showed no significant effect on [Ca2+]i elevation induced by KCl and BHQ in
      Hank's solution containing Ca2+ 1.3 mmol.L-1. These results indicate that TMB-8
      reduced [Ca2+]i via increase of the sarcoplasmic reticulum (SR) sequestration,
      which blocked the release of intracellular store from the SR. However, the
      inhibitory effect of TMB-8 on Ca-influx from extracellular medium seems to be an
      indirect action from the saturation of SR with calcium.

PMID- 11596213
TI  - [Regulation of NGF on intra-synaptosomal free [Ca2+]i in mouse brain].
AB  - In the present study, the influence of direct intrahippocampal injection of NGF
      (nerve growth factor) on synaptosomal free [Ca2+]i in 1-month-old and 18-month
      old mice was observed. The regulation of NGF on synaptosomal free [Ca2+]i in
      vitro was also investigated. The synaptosomal free [Ca2+]i in the main brain
      regions (cerebral cortex, hippocampus, cerebellum, diencephalon) of these mice
      was measured by fluorescent probe Fura-2 of Ca2+ indicator and an AR-CM-MIC
      cation measurement system. The results are as follows: (1) NGF showed no
      detectable effect on hippocampal intrasynaptosomal free [Ca2+]i in 1-month-old
      mice, but appropriate dose of NGF was shown to markedly reduce [Ca2+]i in 18
      month-old mice. (2) Under the condition of low [Ca2+]i level caused by the drug,
      NGF was found to increase [Ca2+]i; conversely, was reduced [Ca2+]i when
      intracellular Ca2+ was overloaded. These results suggest that NGF has dual
      regulation on Ca2+ level in brain and this might be an important mechanism for
      its action in improving memory lesion, in aged person.

PMID- 11596214
TI  - [Protective effects of extract of Ginkgo biloba (EGb) on lysophosphatidylcholine
      induced damages of vascular endothelial cells in vitro].
AB  - Effects of EGb on cultured bovine aortic endothelial cells (BAEC) damaged by
      lysophosphatidylcholine (LPC) were investigated. When endothelial cells were
      incubated with LPC (2.5 micrograms.ml-1) for 24 h, the endothelial cells turned
      round pyknotic, exfoliated and broken, and the contents of malondialdehyde (MDA),
      lactate dehydrogenase (LDH) and plasminogen activator inhibitor (PAI) were
      markedly increased and the superoxide dismutase (SOD) activity was inhibited.
      Treatment with EGb at concentrations of 125 and 250 micrograms.ml-1, caused a
      reduction in MDA, LDH and PAI contents, while the SOD activity in the medium was
      increased and the morphologically damaged BAECs were alleviated. These results
      suggest that EGb afforded protection against BAECs damages induced by LPC and
      that the protective effect of EGb may be due to anti-lipid peroxidation via free
      radical scavenging activity.

PMID- 11596215
TI  - [Effects of nifedipine and cromakalim on isolated rat bladder tissue and aorta
      strip].
AB  - Relaxing effects of nifedipine and cromakalim on rat aorta strip, bladder ring
      and bladder strip were compared on receptor and KCl mediated contraction. The
      IC50 of nifedipine to inhibit NE induced contraction (by stimulation of alpha 1
      adrenoceptor in aorta strip) was found to be 2.76 +/- 0.79 nmol.L-1. For the same
      action the IC50 of cromakalim (a potassium channel opener) was 48 +/- 25 nmol.L
      1. However, to inhibit 27.5 mmol.L-1 KCl induced contraction, the IC50 for
      nifedipine and eromakalim were 1.83 +/- 1.3 nmol.L-1 and 64 +/- 19 nmol.L-1,
      respectively. On bladder ring, to inhibit carbachol mediated contraction (by
      cholinergic M-receptor stimulation), the IC50 for nifedipine and cromakalim were
      found to be 15 +/- 13 nmol.L-1 and 13 +/- 8.0 nmol.L-1, respectively. To inhibit
      KCl induced contraction, the IC50s were 2.05 +/- 1.26 nmol.L-1 and 38 +/- 26
      nmol.L-1. On bladder strip, nifedipine and cromakalim antagonized carbachol
      mediated contraction, with IC50s of 12 +/- 12 nmol.L-1 and 32.0 +/- 2.4 nmol.L-1.
      Both compounds reduced the contraction force mediated by KCl with IC50 of 1.57 +/
      0.7 nmol.L-1 and 71 +/- 25 nmol.L-1, respectively. Our study showed that
      cromakalim was better to relax receptor mediated contraction of bladder ring.
      While, nifedipine was more potent to antagonize NE induced aorta strip
      contraction. Nifedipine also showed greater effect on KCl induced responses in
      all three tissue preperations.

PMID- 11596216
TI  - [Effect of oxyphenamone, a new inodilator, on cardiac hemodynamics in normal rat,
      cat and dog].
AB  - For studying the cardiotonic and vasaodilating effect of oxyphenamone in vivo,
      cardiac hemodynamic variables of anesthetized normal rats, cats and dogs were
      determined with a polygraph and electromagnetic flowmeters. Intravenous injection
      of oxyphenamone (0.5-10 mg.kg-1) dose-dependently decreased the mean arterial
      pressure and systemic vascular resistance moderately and increased cardiac
      output, myocardial contractile force and +/- dT/dtmax. The blood flow of coronary
      and femoral arteries increased markedly and their vascular resistance decreased
      but the blood flow and vascular resistance of cerebral artery did not change.
      Some species differences were observed in the effect of oxyphenamone on heart
      rate (HR) and left ventricular pressure (LVP). Oxyphenamone did not influence the
      HR and LVP in normal cats. It decreased the HR, left ventricular systolic
      pressure (LVSP) and +/- dP/dtmax, while did not affect the left ventricular end
      diastolic pressure (LVEDP) in rats. In contrast, administration of oxyphenamone
      to dogs increased LVSP and +/- dP/dtmax markedly and diminished LVEDP slightly.
      Oxyphenamone decreased HR slightly at lower dosage (1 and 3 mg.kg-1), but
      increased heart rate moderately at high dose (6 mg.kg-1) in dogs. These indicate
      that oxyphenamone has cardiotonic and vasodilating effects in vivo. Whether the
      effects of oxyphenamone on cardiac hemodynamics would be useful for the treatment
      of heart failure should be evaluated further.

PMID- 11596217
TI  - [The synthesis and pharmacological activities of C-galactosides of
      furanosequiterpenes].
AB  - Four new C-galactosides were obtained by treatment of 1-O-trifluoroacetly-2, 3,
      4, 6-tetra-O-benzly-alpha-D-galactopranose with 7-methoxy-6-(3-pentenyl)-3, 5
      dimethylbenzofuran, 7-acetoxy-6-(3-pentenyl)-3, 5-dimethylbenzofuran and 1, 2
      dihydrocacalohastin in the presence of Lewis acid. Their structures and
      compositions were elucidated by elemental analysis and spectroscopic methods. The
      results of the pharmacological test indicated that the sesquiterpenes are calcium
      antagonist but their C-galactosides are calcium agonist.

PMID- 11596218
TI  - [Studies on synthesis and pharmacological activities of cimicifugamide from
      Cimicifuga dahurica, and its analogues].
AB  - The total synthesis of cimicifugamide, a new natural compound isolated from the
      roots of Cimicifuga dahurica, was accomplished by a reaction sequence of seven
      steps in an overall yield of 31%. Trifluoroacetoxy was used as leaving group at
      the anomeric carbon. The target product was characterized by IR, MS, 1HNMR,
      13CNMR and elemental analysis. In addition, seven analogues were synthesized and
      their preliminary pharmacological activities were tested.

PMID- 11596219
TI  - [Studies on the chemical structure of lucyoside R from leaves of Luffa cylindrica
      roem].
AB  - A new pentacyclic triterpenoid saponin, lucyoside R, has been isolated from the
      leaves of Luffa cylindrica along with lucyoside G. Its stucture was established
      as 2 alpha, 21 beta-dihydroxyhederagenin-3-O-beta-D-glucopyranoside based on
      spectral and chemical evidence.

PMID- 11596220
TI  - [Studies on the chemical constitutens of Vicia amoena Fisch].
AB  - One new flavonoide was isolated from Vicia amoena Fisch. On the basis of spectral
      (UV, MS, NMR) and chemical reactions, it was elucidated to be kaempferol-3-O-beta
      D-mannoside, named amoenin(A3). Moreover, five known compounds have been isolated
      and identified as quercetin, kaempferol, quercetin-3-O-alpha-L-rhamoside,
      quercetin-3-O-beta-D-glucoside, kaempferol-3, 7-O-alpha-L-dirhamoside. The total
      flavonoides showed significant effects on inducing hyperlipidemia and increasing
      micro-blood vessel elasticity.

PMID- 11596221
TI  - [Studies on triterpenoids and their glycosides from Aralia dasyphylla Miq].
AB  - The structures of two triterpenoids and their glycosides were isolated from
      Aralia dasyphylla Miq. Their structures have been identified to be oleanoic
      acid(I), 16 beta-hydroxy-18 beta-H-oleanoic acid(II), oleanoic acid-28-O-beta-D
      glucopyranoside(III) and 16 beta-hydroxy-18 beta-H-oleanoic acid-28-O-beta-D
      glucopyranoside(IV), respectively, mainly through interpretation of UV, IR, MS,
      1H and 13CNMR, DEPT, HMQC and HMBC spectra data. The stereochemistry of II has
      been confirmed by NOESY. Pharmacological experiments showed that the total
      saponins exerted preventative effect on CCl4-induced liver injury of male mice
      and hypoglycemic effect on a model of alloxan-induced diabetes in rats.

PMID- 11596222
TI  - [Determination of isosorbide-5-mononitrate in plasma by GC-ECD and study on its
      pharmacokinetics in ten volunteers].
AB  - A rapid, accurate and sensitive gas chromatographic method was developed for the
      determination of isosorbide-5-mononitrate(5-ISMN) in 0.5 ml plasma. The
      instrument was equipped with 5% SE-30 glass packed column (2 m x 3 mm) and
      electron-capture detector. Isosorbide dinitrate (ISDN) was used as internal
      standard. The plasma was extracted with a mixture of ethyl ether and n-hexane
      (4:1) to give mean recoveries of 100.1% of 5-ISMN. The extracts reacted with
      trifluoroacetic anhydride and the derivatives were analyzed. The calibration
      curves were linear over a wide range of concentrations (20-800 ng.ml-1), and the
      detection limit of 5-ISMN was 2.0 ng.ml-1. The precisions (RSD%, n = 5) of within
      day and day-to-day were less than 4% and 6.5%, respectively. The pharmacokinetic
      characteristics of 5-ISMN in ten human volunteers after a single oral dose of 20
      mg 5-ISMN were investigated. The concentration-time curve was fitted to a one
      compartment model.

PMID- 11596223
TI  - [ Studies on some physical characteristics of cyclosporine A (CyA) solid
      dispersions].
AB  - In this paper, poloxamer and PVP were used as carriers. CyA-poloxamer and CyA-PVP
      solid dispersions were prepared using the melting-solvent method or solvent
      method, respectively. The percentage compositions of the solid dispersions ranged
      from 10:90 to 90:10. Hot stage microscopy, powder X-ray diffraction and
      differential scanning calorimetry were used to examine the physical-chemical
      characteristics of the solid dispersions to provide some reliable and scientific
      basis for preformulation of CyA.

PMID- 11596224
TI  - [Determination of puerarin in plasma by high performance liquid chromatography].
AB  - A high performance liquid chromatography with fluorescence detection has been
      developed for determination of puerarin in plasma using a column of YWG-C16 (10
      microns) and mobile phase of methanol (450 ml)-water (522.5 ml)-0.1 mol.L-1
      phosphate buffer (pH 7.4, 27.5 ml). The preparation of samples was as follows:
      Transfer 0.1 ml of plasma into a 1 ml stoppered glass tube containing daidzein as
      internal standard, add 0.4 ml of absolute alcohol to deproteinize the plasma,
      vortex for 2 min, centrifuge for 15 min at 2800 r.min-1 and inject 20 microliters
      of the supernatant into the HPLC column. Linear calibration curve was obtained by
      plotting concentration vs peak height ratio over the range 0.03-12.00
      micrograms.ml-1 with a correlation coefficient of 0.999. The average recovery of
      puerarin was 95.3% and the average RSD was 4.8%. The minimum detectable quantity
      of puerarin was 0.04 ng, equivalent to 10 ng.ml-1 plasma. This method is highly
      sensitive, specific, simple and rapid. The plasma concentration-time course of
      puerarin given i.v. 2.25 mg.kg-1 to two dogs determined by this method was found
      to fit a two-compartments open model with T1/2 alpha of 6.0 min and T1/2 beta of
      57.4 min.

PMID- 11596225
TI  - [Studies on nimodipine sustained-release tablet capable of floating on gastric
      fluid with prolonged gastric resident time].
AB  - Nimodipine was incorporated into poloxamer 188 solid dispersion before
      formulation, then mixed excipient and solid dispersion were directly compressed
      into nimodipine floating sustained-release tablet(NM-FSRT). Formulations were
      optimized using uniform design and variables affecting nimodipine release from
      matrix were studied. Preliminary in vivo evaluation was carried out in healthy
      volunteers. Results showed that the optimized formulation could remain floating
      on gastric fluid for over 10 hours. In vitro release(0.15-6 h) conformed to zero
      order kinetics. Hydroxypropylmethylcellulose(HPMC) and polyethylene glycol
      6000(PEG 6000) showed the biggest effect on in vitro drug release. Increasing
      HPMC content and decreasing PEG 6000 content led to decrease of nimodipine
      release in vitro. NM-FSRT did remain floating on gastric fluid with prolonged
      gastric resident time(GRT) of 5 hours under fed condition, while GRT was only 3
      hours under fasted condition. GRT of nimodipine conventional tablet(NM-CT) under
      fed and fasted conditions was 3 and 2 hours, respectively. Relative
      bioavailability of NM-FSRT was 391.46% and MRT was over twice that of NM-CT. NM
      FSRT appeared to have prolonged GRT and improved bioavailability.

PMID- 11596226
TI  - [Determation of strychnine and brucine in Strychnos by HPLC].
AB  - This paper describes the determination of strychnine and brucine in the seeds,
      root, stem and leaves of Strychnos species by HPLC. The analytical column used
      was ZY110 YNG-C18. The mobile phase was KH2PO4(0.01 mol.L-1)--MeOH(73:27), pH2.5,
      regulated by 10% H3PO4. Flow rate was 1.0 ml.min-1. The detection wavelength was
      264 nm. The linear ranges of strychmine and brucine were 0.18-7.26 micrograms and
      0.11-4.32 micrograms, respectively. The recoveries of strychnine and brucine were
      98.27% and 98.04%, respectively. The analytical results showed that the contents
      of strychnine and brucine in samples showed great difference between different
      species. The contents of strychnine in the seeds of Strychnos wallichiana and S.
      ignatii were 5.6% and 3.9%, respectively. These results show that the two
      Strychnos species may be developed as the resources of strychnine.

PMID- 11596227
TI  - [Progress in studies on liquid chromatography-electrospray ionization mass
      spectrometry of proteins and peptides].

PMID- 11596228
TI  - [A survey on botanical origins of drug tiannanxing produced in Sichuan].
AB  - According to the investigation and identification of botanical origins of 7
      species and 1 variety of the traditional Chinese drug Tiannanxing produced in
      Sichuan, it has been found out that the main species available on the market are
      Arisaema erubescens and A. heterophyllum, while A. asperatum, A. wilsonii and A.
      fargesil come second. A key for their identification is presented in this paper.

PMID- 11596229
TI  - [A histochemical study on baicalin].
AB  - Baicalin in the root of Scutellaria baicalensis was analysed histochemically by
      means of TLC and HPLC. It was determined that the content of baicalin in phloem
      was 11.08%, in xylem 7.86%, in phellem 2.19% and in centric decayed part 0.815%.
      Thus the quality of root of Scutellaria baicalensis is believed to consist in
      thin phellem, high ratio of phloem to xylem and absence of centric decayed part.

PMID- 11596230
TI  - [A study on the nutrient physiology of Ophiopogon japonicus (Thunb.) Ker-Gawl].
AB  - By means of observing at regular intervals and on tixed plants, the growth
      stages, organogenetic habits, content of nutrient elements and its changing
      regularity, storage habit of dry matter, relationship between aerial and
      subterraneous parts, and fertilizer requirements have been studied for Ophiopogen
      japonicus.

PMID- 11596231
TI  - [Influence of processing methods on alkaloid, toxicity and effect of Strychnos
      nux-vomica L].
AB  - Determination has been made on the contents of strychnine, brucine and ephedrin
      in different processed products of Strychnos nux-vomica. The acute toxicity,
      analgesic and antiphlogistic actions of these products have also been detected.
      The result shows that the product processed with Ephedra sinica can reduce
      toxicity and promote curative effect. Among the different processing methods the
      preparation with Ephedra and Liqorice root and the preparation with Ephedra and
      alcohol appear better and thus useful in practical application.

PMID- 11596232
TI  - [Verification of a new processing technology for pilot production of Aconitum
      coreanum (Levl.) Raipaics].
AB  - The stability and feasibility of a new technology for processing Aconitum
      coreanum have been tested for pilot production by determining the components,
      toxicity(LD50) and traditional identification standard. The result shows that the
      contents of guanfu A and total alkaloid between the small trial and pilot
      production are slightly different and LD50 are nearly similar. Hypaconitine was
      not found in all kinds of processed products. The new technology has thus been
      proved stable and feasible.

PMID- 11596233
TI  - [Determination of paeonol in jiawei xiaoyao granules by HPLC].
AB  - A HPLC method has been used for the determination of paeonol in Jiawei Xiaoyao
      Granules. The method is simple and accurate. The average recovery is 96.48% and
      relative standard deviation 1.11%. The method can be used for quantitative
      analysis of these granules.

PMID- 11596234
TI  - [Chemical constituents of the root of Epimedium acumiantum Franch].
AB  - Four known flavonol glycosides, ikarisoside A(I), 2"-O-rhamnosyl-icariside II
      (II), 2"-O-rhamnosyl-ikarisoside A(III) and ikarisoside B(IV) were isolated from
      the ethyl acetate extract of the root of Epimedium acuminatum. Their structures
      were elucidated by spectroscopic and chemical methods. II, III and IV were
      isolated from this plant for the first time.

PMID- 11596235
TI  - [Chemical constituents of the stem and root of Syzygium buxifolium Hook. Et Arn].
AB  - Six crystalline substances were isolated from the stem and root of Syzygium
      buxifolium and identified as friedelin, beta-sitosterol, ursolic acid, pomolic
      acid, oleanolic acid and beta-daucosterol.

PMID- 11596236
TI  - [Chemical constituents of tissue cultures of Salvia miltiorrhiza Bunge].
AB  - Two compounds were isolated from the tissue cultures of Salvia miltiorrhiza for
      the first time, and identified as danshenxinkun B and Ro-09-0680 by spectroscopic
      methods.

PMID- 11596237
TI  - [Chemical constituents of radix Angelicae Sinensis].
AB  - Six compounds were isolated from Radix Angelicae Sinensis and identified as (E)
      ligustilide, (Z)-ligustilide, (Z)-n-butylidene phthalide, palmitic acid, beta
      sitosterol and ferulic acid.

PMID- 11596238
TI  - [Protective effects of folium Ginkgo extract on experimental cerebral ischemia of
      mice].
AB  - Folium Ginkgo extract(EGb761) has been proved able to significantly prolong the
      survival time of mice suffering from cerebral ischemia induced by occluding
      bilateral common carotids, and reduce the inhibition of cerebral GSH-Px and Na(+)
      K(+)-ATPase activities during reperfusion processes of these mice. Pretreatment
      with EGb761 also helps alleviate the subcellular damages in hippocampus of
      cerebral ischemic mice.

PMID- 11596239
TI  - [Antivirus effect of polysaccharides of brewer yeast in vitro].
AB  - The antivirus effect of polysaccharides of brewer yeast from yeast mud on 13
      kinds of viruses including DNA and RNA virus along with their mechanisms were
      studied. The result showed that this effect was remarkable on the infections with
      poliovirus III, adenovirus III, ECHO6 virus, enterovirus 71, vesicular stomatitis
      virus, herpesvirus I, II, coxsackie A16 virus and coxsackie B3 virus. The
      polysaccharides of brewer yeast could also inhibit the development of cytopathic
      effect(CPE) and protect cultural cells from being infected with the above
      viruses.

PMID- 11596240
TI  - [Effect of total saponins of Panax notoginseng (TSPNS) on myocardial
      intracellular Ca2+ and activity of calcium pump of membrane of sarcoplasmic
      reticulum in SHR].
AB  - A comparative study was conducted on the action of TSPNS, NS and Captopril in
      treating SHR, with WKY of similar ages taken as normal control. The results
      demonstrate that TSPNS helps increase the effect of calcium pump on the membrane
      of sarcoplasmic reticulum, decrease the myocardial intracellular Ca2+ and reduce
      the mass of the left ventricular muscle.

PMID- 11596241
TI  - [A review of pharmacological study on Epimedium grandiflorum Morr and its active
      constituents].

PMID- 11596242
TI  - [Identification of Tougucao derived from Clematis species].
AB  - Comparative studies were carried out on the morphology and histology of 5
      Clematis species, namely, C. intricata, C. aethusifolia, C. glauca, C. tangutica
      and C. hexapetala, allegedly used as "Tougucao". New characteristics, a
      sclerenchymatous ring composed of primary phloem fibers and lignified parenchyma
      cells, and a parenchymatous tertiary ring were discovered. A parameter
      representing the ratio of the diameter of cambium ring to the diameter of the
      stem (RCR) is created. A key for identification of the stems of the above five
      species is made according to the presence or absence of the sclerenchymatous
      ring, the diameter and numbers of hair cells, the thickness of fiber wall and the
      value of RCR, etc.

PMID- 11596243
TI  - [Soil conditions for growth of Ophiopogon japonicus ker.-gawl].
AB  - Field investigation and laboratory analysis were made on the formation
      conditions, as well as physical and chemical properties of soils for growth of
      Ophiopogon japonicus.

PMID- 11596244
TI  - [A preliminary study on alternation of generations of Cordyceps sinensis (Berkey)
      Sacc].
AB  - The insect pathogeny of parasitic hepialus by Cordyceps sinensis is, reported in
      this paper. The infestation of hepialus larvae by Cordyceps sinensis, growth and
      reproduction of hypha body in the hemolymph of host larvae, growth of stroma,
      maturity of hymenium and the abjection and germination of ascospores were
      observed.

PMID- 11596245
TI  - [Peroxidase in Glycyrrhiza uralensis Fisch. at primary stage of sprouting].
AB  - Changes of the peroxidase in Glycyrrhiza uralensis were detected by
      electrophoresis and spectrophotometric analysis at the primary stage of
      sprouting. The result shows that during the process of seed sprouting and radicle
      elongating, the activities of peroxidase keep increasing, some new bands being
      detected and some original bands enhancing. The changes take place slowly within
      24 h, but become faster after 24 h.

PMID- 11596246
TI  - [Quality standards of processed nutmegs].
AB  - The quality standards of nutmeg and its processed products were studied in such
      aspects as volatile oil content, extract determination, moisture content,
      microscopic characteristics, thin-layer chromatography, and so on. This provided
      a basis for drawing up the quality standards.

PMID- 11596247
TI  - [Effect of different processing conditions on content of myrisiticin, volatile
      oil and fatty lipid in semen Myristicae].
AB  - The effect of different processing conditions on contents of myrisiticin,
      volatile oil and fatty lipid in Semen Myristicae was studied by orthogonal
      design. The result shows that these processing conditions could not influence the
      contents of myrisiticin, volatile oil and fatty lipid in the processed products
      of Semen Myristicae, suggesting that processing does not necessarily lower
      toxicity.

PMID- 11596248
TI  - [Quality control for huoxiang-zhengqi liquid].
AB  - The Rhizoma Atractylodis, Cortex Magnoliae Officinalis and Pericarpium Citri
      Reticulatae in Huoxiang-zhengqi Liquid were identified by TLC. The total contents
      of magnolol and honokiol were determined by HPLC to be no less than 1.9 mg/ml,
      with an average recovery of 104.4% and 103.3%, RSD 1.23% and 0.91% respectively.

PMID- 11596249
TI  - [A research on chemical dynamic changes and drug efficacy of SMS compound
      prescription: chemical researches on shenmaisan prescription (I)].
AB  - To clarify the material base of the distinct curative effect of Shengmaisan (SMS)
      compound prescription, a study was made on the dynamics of chemical constituents
      in the decoction prepared according to the compound prescription. From the
      decoction a new compound was isolated and identified by UV, IR, MS and NMR as 5
      hydroxymethy-2-furaldehyde (5-HMF). The study suggests that the distinct curative
      effect of SMS compound prescription hinges on a material base which is different
      chemically from that in the other three single drugs used separately, thus
      presenting scientific criteria for rational compatibility and quality check in
      making preparations on compound prescriptions.

PMID- 11596250
TI  - [Chemical constituents of Taraxacum sinicum Kitag].
AB  - Five compounds were separated from Taraxacum sinicum by means of solvent
      extraction and rechromatography on silical gel. Their structures were established
      as caffeic acid, ferulic acid, chlorogenic acid, luteolin and diosmetin by
      spectral analysis and chemical evidence. All the compounds were isolated from
      this plant for the first time. Chlorogenic acid and diosmetin have not been
      discovered from Taraxacum genus previously.

PMID- 11596251
TI  - [A flavonoid compound in Ginkgo biloba L. leaves].
AB  - One compound was isolated for the first time from ethyl acetate extract of Ginkgo
      biloba leaves and identified as kaempferol-3-O-rhamnoside by spectroscopic
      methods.

PMID- 11596252
TI  - [Analysis of essential oil from rhizoma Zingiberis by GC-MS].
AB  - Sixty-six chemical components of the essential oil from Rhizoma Zingiberis were
      identified. The contents of these components were determined by GC-MS. The major
      components were camphene, beta-phellandrene and 1,8-cineole.

PMID- 11596253
TI  - [Determination of adenosine and 3'-deoxyadenosine in Cordyceps militaris (L.)
      Link. by HPLC].
AB  - The establishment of a quantitative determination method by HPLC for adenosine
      and 3'-deoxyadenosine in Cordyceps militaris is reported. The sample was
      extracted with water under ultrasonic management for 2 hours. Chromatographic
      conditions: YWG C18 10 microns 5 mm x 200 mm; mobile phase consisted of NaH2PO4
      NaOH buffer solution (pH 6.8); UV detection at 260 nm. The recoveries of
      adenosine and 3'-deoxyadenosine were 95.8% +/- 0.64% and 100.6% +/- 0.65% (n = 5)
      respectively.

PMID- 11596254
TI  - [Effects of the glucoprotein component of musk on functions of rat
      polymorphonuclear leukocytes activated by LTB4 in vitro].
AB  - To investigate the effects of musk-1, a glucoprotein component isolated from the
      water extract of musk, on some functions of rat polymorphonuclear leukocytes
      activated by LTB4, an in vitro incubation system with rat polymorphonuclear
      leukocytes was used. The superoxide anion production was determined by cytochrome
      C reduction, and the beta-glucuronidase and lysozyme release was quantitated by
      enzyme reactions in which phenolphthaleinglucuronic acid and micrococcus
      lysodeikticus were used as the substrates. In comparison with the control, musk-1
      at final concentrations of 1 microgram/ml-100 micrograms/ml can increase the
      superoxide anion production by 28.7%-202.1% and decrease the beta-glucuronidase
      and lysozyme release by 3%-46% and 6%-32% respectively in rat polymorphonuclear
      leukocytes. It is concluded that musk-1 can significantly affect the functions of
      rat polymorphonuclear leukocytes activated by LTB4. One of the mechanisms of this
      anti-inflammatory action of musk may consist in the inhibition of lysosomal
      enzyme release.

PMID- 11596255
TI  - [An antimicrobial experimental study on the traditional drug Anuqitabiao used by
      the Yi minority nationality].
AB  - The result of experimental study on the antimicrobial effect in vitro of the
      decoction, water-soluble ingredients and liposoluble ingredients of Anuqitabiao
      shows that decoction and water-soluble ingredients have certain inhibitory effect
      on all the tested bacteria, while the liposoluble ingredients do not, indicating
      the antimicrobial ingredients to be water-soluble. The result of antimicrobial
      experiment in vivo shows that neither different concentrations nor different
      separated parts of the decoction have any obvious protective effect on the
      pneumonococci-infected or staphylococciaureus-infected mice.

PMID- 11596256
TI  - [Quantitative determination of ursolic acid in Herba cynomorii by ultraviolet
      spectrophotometry].
AB  - Ursolic acid was isolated form Herba Cynomorii by thin layer chromatography and
      was quantitatively determined by ultraviolet spectrophotometry. The results
      indicate that the content of ursolic acid is 0.78%. The average recovery rate of
      ursolic acid is 97.4%, RSD = 0.45% (n = 4).

PMID- 11596257
TI  - [The effect of Rhodiola capsules on oxygen consumption of myocardium and coronary
      artery blood flow in dogs].
AB  - It has been proved that Rhodiola Capsules can obviously decrease the oxygen
      consumption of myocardium and oxygen consumption index in anesthetic dogs,
      decrease the coronary artery resistance, but have no marked effect on the
      coronary artery blood flow. The Capsules also have the function of decreasing
      blood presure and slowing heart rate.

PMID- 11596258
TI  - [Effect of Acorus tatarinowii Schott. on gastrointestinal myoelectric activity in
      rats].
AB  - The effect of Acorus tatarinowii on the gastrointestinal myoelectric activity and
      mechanism in rats was studied electrio-physiologically. The result indicates that
      Acorus tatarinowii helps inhibit the gastrointestinal myoelectric activity. This
      inhibitory effect is believed to take place through the blocking of cholinergic M
      and non-cholinergic M receptors, and has nothing to do with adrenergic alpha and
      beta receptors.

PMID- 11596259
TI  - [The effects of allitridum on the proliferation of rabbit aortic smooth muscle
      cells in vitro].
AB  - The effects of allitridum on the proliferation of cultured rabbit aortic smooth
      muscle cells (SMC) were studied with SMC incorporation data of 3H-thymidine(3H
      TdR) and contents of superoxide dismutase(SOD), lipid peroxide(LPO),
      prostacyclin(PGI2) and cyclic adenosine monophosphate(cAMP) in medium. The
      results showed that allitridum could inhibit SMC proliferation by increasing SOD
      activity, decreasing LPO, raising PGI2 and cAMP(all P < 0.05-0.01), and the
      inhibitory action was accompanied by the dose-effect relation.

PMID- 11596260
TI  - [Progress in the study of hypoglycemic action of the active constituents of
      Chinese herbal drugs and their therapy of type 2 diabetes mellitus].

PMID- 11596261
TI  - [Textual research on herb youba].
AB  - A textual research has been conducted to clarify the botanical origin of the herb
      Youba in ancient medicinal literatures. The name Youba in (Xin Xiu Ben Cao)
      published in the Tang dynasty and (Ben Cao Gang Mu) published in the Ming dynasty
      has been confirmed to be the immature tuber of Pinellia pedatisecta (without
      branches around the tuber), whereas the same name Youba in (Zhi Wu Ming Shi Tu
      Kao) published in the Qing dynasty refers to Arisaema yunnanense.

PMID- 11596262
TI  - [Anatomy of Aconitum finetianum Hand.-Mazz].
AB  - The primary xylem of plump taproot of Aconitum finetianum is the diarch with
      xylem in the center. In the action of the secondary structure of the herb, the
      meristem is first produced in the secondary phloem, then the anomalous cambium is
      produced in the secondary xylem forms a new and splits into anomalous structure.
      In the action of anomalous structure of the herb, the meristem in the secondary
      phloem sinks inwardly from many sites, and forms many rings with the anomalous
      cambium. One of these rings forms a special endodermis and the protostele turns
      into the schizogenous stele.

PMID- 11596263
TI  - [Identification of powdered Bungarus multieinctus Blyth and its adulterants].
AB  - This paper reports the results of identification of powdered Bungarus
      muliteinctus and its adulterants (Natrix annularis; Dinodon rufozonatum and
      Bungarus fascitus). A comparative table of and a key to the characteristics are
      given.

PMID- 11596264
TI  - [RP-HPLC determination of water-soluble active constituents and oleanolic acid in
      the fruits of Ligustrum lucidum Ait. collected from various areas].
AB  - The contents of p-hydroxyphenethyl-beta-D-glucoside, specnuezhenide and oleanolic
      acid in the fruits of Ligustrum lucidum collected from various areas in China
      were determined by reverse phase high performance liquid chromatography. The
      results could be used to evaluate the quality of the crude drug more
      comprehensively.

PMID- 11596265
TI  - [Preliminary analysis and isolation of genomic total DNA in Fritillaria
      thunbergii Miq].
AB  - Genomic total DNA of leaf, fresh scale and dry scale in Fritillaria thumbergii
      were isolated by two different methods and analysed by agarose gel
      electrophoresis. The results show that the DNA contents are different under these
      two isolating methods. Two bands besides the band of genomic total DNA have been
      found by electrophoresis, these two bands deserve further study.

PMID- 11596267
TI  - [Screening of enhancers for permeation of berberine in ruyi patcher in vitro].
AB  - To screen the best kinds and doses of enhancers for Ruyi Patcher, the effect of
      azonc(A) and propanediol (P) on the permeation of berberine(BR) from Ruyi Patcher
      in vitro was studied using improved Franz diffuse cells and the permeated
      berberine was determined by HPLC. The result showed that 3% of A in combination
      with 10% of P had synergistic effect, which helped enhance the skin permeation of
      BR significantly(P < 0.01). Therefore, a combination of 3% A and 10% P is the
      best enhancer for Ruyi Patcher and the penetration process of BR could be
      described by one-order kinetics.

PMID- 11596266
TI  - [A study on processing of the root of Astragalus membranaceus Bge. by HPLC].
AB  - The paper presents a study on the drug-processing of the root of Astragalus
      membranaceus. A HPLC method for the determination of astragaloside IV in its
      processed products has been established. The recovery is 96.1% and the RSD is
      2.15%.

PMID- 11596268
TI  - [Saponins in Bupleurum smithii Wolff var. parvifolium Shan et Y. Li].
AB  - Five saikosaponins and two saikosapogenins were isolated from the roots of
      Bupleurum smithii var. parvifolium by column chromatography, preparative-TLC and
      HPLC, and identified as saikosaponin a, saikosaponin d, saikosaponin b2,
      saikosaponin b4, chikusaikoside I, saikogenin F and saikogenin G on the basis of
      spectral analysis. All of them were isolated from this plant for the first time.

PMID- 11596269
TI  - [Chemical studies on Pyrrosia gralla (Gies.) Ching].
AB  - From Pyrrosia gralla four compounds were isolated and identified stigmasterol(I),
      ursolic acid (II), mangiferin(III) and sucrose(IV) by physical and chemical
      means. Compounds I and II were obtained from Pyrrosia for the first time.

PMID- 11596270
TI  - [Effects of rifampin and isoniazid on the pharmacokinetics of diazepam in
      rabbits].
AB  - The pharmacokinetics of diazepam (3 mg.kg-1, i.v.) in rabbits was studied after
      pretreatment with rifampin (RFP, 100 mg.kg-1.d-1 x 4), isoniazid (INH, 50 mg.kg
      1.d-1 x 4) and RFP + INH. The results showed that RFP significantly increased
      cytochrome P-450 content, but the T 1/2 and AUC of diazepam were significantly
      decreased. The plasma clearance (CL) was increased in the RFP group. In the INH
      group the T 1/2 and AUC of diazepam were significantly increased and the CL was
      significantly decreased. However, cytochrome P-450 content and the
      pharmacokinetic parameters of diazepam were not changed in the RFP + INH group.
      Our results indicate that RFP induces the activity of hepatic microsomal enzymes
      and increases the metabolism of diazepam, INH inhibits the activity of hepatic
      microsomal enzymes and decreases the metabolism of diazepam in rabbits.

PMID- 11596271
TI  - [Effects of calcium inhibitor on hydrogen peroxide-induced damage and calcium
      influx in bovine aortic endothelial cells in culture].
AB  - Hydrogen peroxide(H2O2)-induced cell damage and Ca2+ influx into bovine aortic
      endothelial cells (BAEC) were investigated. Our data suggested that H2O2 could
      dose- and time-dependently induce damage in cultured BAEC assessed by 3-(4, 5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay and increase
      malondialdehyde (MDA) production, which reflects the level of lipid peroxidation.
      Exposure of BAEC to H2O2 (100 mumol.L-1) caused significant increase in
      intracellular free calcium ([Ca2+]i) within 6 min, suggesting that the increase
      of [Ca2+]i might implicate in H2O2-induced cell damage. The calcium inhibitor
      nifedipine was found to dose-dependently decrease the increase of [Ca2+]i caused
      by H2O2 and protect BAEC against H2O2-induced damage reflected by significant
      decrease of MDA production and increase of MTT value. These results indicate that
      overload of calcium might be responsible to some extent causing oxidative damage
      to cells.

PMID- 11596272
TI  - [Sertindole, a novel alpha 1A-adrenoceptor selective antagonist].
AB  - The antagonism effect of sertindole on alpha 1-AR subtypes was studied by
      combining radiologand binding assays in three cloned alpha 1-AR subtypes stably
      expressed in human embryonic kidney 293 cells and contractile response experiment
      in isolated rat blood vessels. The results showed that the affinity for
      sertindole in the cloned alpha 1A-AR (pKI 8.90 +/- 0.17) was 69-fold (pKI 7.06 +/
      0.09) and 132-fold (pKI 6.78 +/- 0.07) higher than that for the cloned alpha 1B-
      and alpha 1D-AR, respectively. The pA2 values for sertindole in antagonizing NE
      induced vasoconstriction in isolated rat aorta and renal artery were shown to fit
      well to the pKI values on cloned alpha 1D- and alpha 1A-AR, respectively.
      Pretreatment of membrane preparations with sertindole for 30 min significantly
      reduced the maximal binding capacities. (Bmax) of 125 IBE2254 to the three cloned
      alpha 1-AR subtypes without alteration of affinities (KD values). In the presence
      of sertindole, the Bmax of 125IBE2254 binding to the cloned alpha 1-ARs were not
      significantly changed, while the KD values were significantly increased. Thus,
      sertindole is a selective irreversible competitive alpha 1-AR antagonist with
      alpha 1A subtype.

PMID- 11596273
TI  - [Effects of differentiation status on apoptosis of human leukemia HL60 cells].
AB  - The effects of differentiation of human leukemia HL60 cells on harringtonine(Har)
      and camptothecin(Cam) induced apoptosis(in these cells) were studied. When
      treated with phorbol 12-myriate, 13-acetate 16 nmol.L-1 for 24 h, the HL60 cells
      differentiated into monocyte/macrophage cells and were arrested at G1 phase. The
      differentiated cells were shown to be resistant to the Har and Cam induced
      apoptosis, but showed no change of expression of c-myc gene. HL60 cells incubated
      in 1.4% dimethyl sulfoxide for 48 h differentiated into granulocyte cells and
      were also gene arrested at G1 phase. The differentiated cells became resistant to
      the apoptosis induced by Cam, but not that by Har, and expression of c-myc
      decreased drastically in the differentiated cells. The results indicate that the
      differentiated status of human leukemia HL60 cells apparently affected the
      apoptosis induced by harringtonine and camptothecin, but it was irrelevant to the
      change of the expression of c-myc gene.

PMID- 11596274
TI  - [Effect of sanchinoside Rg1 on experimental thrombosis and its mechanisms].
AB  - The effect of sanchinoside Rg1 on generation of thrombosis and its mechanism was
      studied. Rg1 was shown to markedly inhibit experimental thrombosis formation
      induced by extra corporeal shunt between the carotid artery and jugular vein.
      After Rg1 infusion, the activity of t-PA was found to be increased, so did the
      percentage of active-type t-PA, but the activity of PA-I decreased. Further data
      in our study indicate that incubation of endothelial cells with Rg1 for 24 h
      caused significant increase of NO production. This effect was found to be dose
      dependent. These observations suggest that Rg1 is a potent anti-thrombosis
      substance and can enhance the function of fibrinolysis system and stimulate
      vascular endothelial cells to release NO.

PMID- 11596275
TI  - [The effect of a new cholinolytic-[3H] tricyclopinate on human brain muscarinic
      receptors].
AB  - The binding characteristics of the novel cholinergic antagonist [3H]
      tricyclopinate with muscarinic receptors from human cerebral cortex were
      investigated in comparison with [3H] QNB by performing radioligand binding
      assays. As revealed by saturation experiments, the binding parameters of [3H]
      tricyclopinate (Kd = 0.044 nmol.L-1, Bmax = 514 fmol.mg-1) were almost identical
      with those of [3H]QNB (Kd = 0.040 nmol.L-1, Bmax = 508 fmol.mg-1). Both ligands
      fit a one site model of receptor-ligand interaction. Tricyclopinate showed a
      potency comparable to QNB on muscarinic receptors in inhibition experiments.
      However, some differences also existed between tricyclopinate and QNB. Kinetic
      experiments showed that both the association and dissociation of tricyclopinate
      (K1 = 1.40 (nmol.L-1)-1.min-1, K2 = 0.39 min-1) with muscarinic receptors were
      quicker than QNB (K1 = 0.65 (nmol.L-1)-1.min-1, K2 = 0.005 min-1). In addition,
      tricyclopinate behaved differently from QNB in the response of the dissociation
      profile to the allosteric modulation of gallamine. These results demonstrated
      that tricyclopinate has comparable affinity to muscarinic receptors with QNB but
      might interact with them in a different way. The introduction of [3H]
      tricyclopinate might complement the use of [3H] QNB in the study of central
      muscarinic receptors.

PMID- 11596276
TI  - [Antagonizing effect of sodium ferulate on the changes of hepatic antioxidative
      function induced by ethanol in mice].
AB  - Effects of ethanol at different dosages on hepatic antioxidative and detoxicating
      functions and the antagonizing effect of sodium ferulate have been investigated
      in mice. The data showed that ethanol (11.4 g.kg-1, ig) could induce the increase
      of hepatic glutathione peroxidase (GSH-Px) activity and decreases of hepatic
      glutathione reductase (GSH-Re), superoxide dismutase (SOD) and glutathione S
      transferase (GST) activities and reduce glutathione (GSH) content. At the same
      time, serum GST activity was increased. Pretreatment with sodium ferulate (100
      mg.kg-1 ig, qd x 10 d) completely reversed these changes induced by ig ethanol in
      mice, indicating that sodium ferulate could protect mice from ethanol-induced
      acute hepatotoxicity. The hepato-protective mechanism of sodium ferulate may be
      related to intensification of the function of glutathione oxidative-reductive
      enzymes, enhancement of SOD activity and promotion of glutathione conjugation.
      The results also indicate that the serum GST level is a sensitive indicator in
      ethanol-induced hepatotoxicity.

PMID- 11596277
TI  - [Synthesis and biological activity of tyrosine protein kinase inhibitors].
AB  - Four classes of 25 tyrosine protein kinase (TPK) inhibitors were designed and
      synthesized. Compounds 1-10 were tested to inhibit TPK of HL-60 leukemia cell
      using 32P-ATP method, and some of them exhibit evident inhibitory activities.
      Their structure-activity relationship is similar to that of TPK inhibitors
      reported in literatures. Compounds 11-25 were tested to inhibit TPK of normal rat
      spleen cell using ELISA method and their SAR is different from that using 32P-ATP
      method.

PMID- 11596278
TI  - [Studies on the chemical constituents of Gynostemma longipes C.Y. Wu].
AB  - A new triterpenoid saponin named gylongiposide I was isolated from the aerial
      parts of Gynostemma longipes C.Y. Wu. On the basis of chemical evidence and
      spectral data the structure of gylongiposide I was elucidated as 19-oxo-3 beta,
      20(S), 21-trihydroxydammar-24-ene-3-O-([alpha-L-rhamnopyranosy(1-->2)] [beta-D
      xylpyranosyl(1-->3)]) alpha-L-arabinopyranoside (G). The known compounds were
      identified as gypenoside XLIX(F) and ginsenoside Rb1(A).

PMID- 11596279
TI  - [The structural elucidation of new polyoxygenated cyclohexenes from Uvaria
      grandiflora].
AB  - Four new polyoxygenated cyclohexenes, named uvarigranol A(1), B(2), E(3) and
      F(4), along with the known zeylenol were obtained from the roots of Uvaria
      grandiflora Roxb (Annonaceae). Based on spectral and X-ray analysis as well as
      Mosher methodology, their structures and absolute configuration were established.

PMID- 11596280
TI  - [Study of magnetic microspheres for purging cancer cells from bone marrow. II.
      Preparation of polystyrene magnetic microspheres. ].
AB  - Magnetic microspheres (MS) used to purge tumor cells from human bone marrow were
      prepared with a two step method. Main factors that can influence the
      magnetization result were discussed. The MS were coated with polyacrolein which
      has active aldehyde group. The magnetic material content and the magnetic
      response of MS were determined and showed that the magnetic material y-Fe(2)O(3)
      by X-ray diffraction.

PMID- 11596281
TI  - [Determination of permeation of ketoprofen across the skin in vitro by second
      order derivative spectrophotometry].
AB  - A second order derivative spectrophotometric method was developed for the
      permeative determination of ketoprofen in vitro. The method can avoid the
      disturbance of skin tissue. The procedure is simple and rapid. The results are
      accurate. The mean recovery of ketoprofen is 99.00% +/- 1.51%.

PMID- 11596282
TI  - [High performance liquid chromatographic assay for aceclofenac in plasma and its
      pharmacokinetics in dogs].
AB  - A sensitive and simplified high performance liquid chromatographic procedure has
      been developed for the quantification of aceclofenac and its major metabolite in
      dog plasma. The recovery of aceclofenac was 91.3%-96.9%. The relative standard
      deviation was 3.69%-8.13%. The calibration curve was linear in the range from
      0.050 microgram.ml-1 to 51.2 micrograms.ml-1 with gamma = 0.9998. The detection
      limit of the method is 10 ng.ml-1 for aceclofenac. Plasma concentrations of both
      aceclofenac and its major metabolite were simultaneously determined. After oral
      medication of aceclofenac to dogs at the dose of 2.5 mg.kg-1, the drug was
      absorbed rapidly and reached its peak level in plasma at about 12 min. The plasma
      drug concentration-time course conformed to a 2-compartment open model with a
      first order absorption. The mean value of T1/2 alpha and T1/2 beta for
      aceclofenac were 2.5 min and 137 min respectively. Plasma diclofenac
      concentration, a major metabolite of aceclofenac, reached its maximum at about
      110 min, the mean Cmax for diclofenac was 3.2 micrograms.ml-1. The mean terminal
      elimination half-life for diclofenac was 140 min.

PMID- 11596283
TI  - [Identification of semen Cuscutae by HPCE].
AB  - A method for identification of semen Cuscutae, a traditional Chinese herb, was
      developed. The proteins in semen Cuscutae were extracted under acid or basic
      conditions and separated by high performance capillary electrophoresis. The
      electrophoretograms of acidic or basic extractants from Cuscuta chinensis Lam.,
      Cuscuta australis R. Br. and Cuscuta japonica Choisy showed significant
      differences, which can be used to identify the three different semen Cuscutae.
      The results of the identification for 13 pharmacognosical samples agreed well
      with those of scanning electronic microscopy and tissue microanalysis.

PMID- 11596284
TI  - [Studies on sultamicillin hydrolysis].
AB  - Sultamicillin is an oral mutual pro-drug composed of double esters of
      formaldehyde hydrate in which one of the hydroxyl groups is esterified with
      ampicillin and the other with sulbactam. It is hydrolyzed fast in neutral or
      weakly alkaline condition. When hydrolyzed, it forms ampicillin and
      hydroxylmethyl sulbactam or sulbactam and hydroxylmethyl ampicillin by different
      routes. Usually, the former has priority as the two ester bonds have different
      activities. The ratio of ampicillin to sulbactam in the products is about 3:1.
      Both the hydroxylmethyl sulbactam and the hydroxylmethyl ampicillin can be
      further catalyzed by esterase to produce formaldehyde.

PMID- 11596285
TI  - [Determination of amoxicillin in human plasma by high performance liquid
      chromatography and its pharmacokinetics].
AB  - A rapid and sensitive assay for amoxicillin in human plasma has been developed
      using reversed phase high performance liquid chromatography. Plasma samples were
      prepared for analysis by addition of internal standard (tinidazole) followed by
      protein precipitation with HClO4. A YWG C18H37 column as stationary phase and a
      0.033 mol.L-1 phosphate buffer (pH 7.2)--methanol mixture (85:15) as mobile phase
      were used with the UV detector set at 229 nm. The calibration curve was linear in
      the range from 0.2 microgram.ml-1 to 20.0 micrograms.ml-1 with gamma > 0.999. The
      analytical recovery of amoxicillin from plasma was > 86.7%. The relative standard
      deviations for within-day and between-day were < 5.48% and < 8.29%, respectively.
      Following oral administration of 500 mg in human volunteers, the peak levels of
      amoxicillin in plasma averaged 6.88 +/- 2.25 micrograms.ml-1 at 84.4 +/- 21.1
      min. The mean half life time for amoxicillin was 62.8 +/- 14.6 min.

PMID- 11596286
TI  - [A study on the metabolites of dl-3-n-butyphthalide in rats].
AB  - The metabolites of dl-3-n-butylphthalide(NBP), a novel drug with promising
      protective action against cerebral ischemia, was studied in rats. Two main in
      vitro metabolites of NBP, M I and M II, were isolated and purified from rat liver
      microsome incubating system by using HPLC. The structure elucidation was mainly
      accomplished by spectral studies(UV, 1H-NMR, MS). Within 24 h following i.g. 3H
      NBP, the total radioactivity excreted in urine and feces was 73.7% of the dose.
      Comparing with previous study, within 72 h following i.g. NBP, the total
      prototype drug excreted in urine and feces was 2.53% of the dose. This result
      excludes the possibility that NBP accumulates in vivo. The urine and brain
      homogenate of the rats(i.g. 3H-NBP) were analyzed by TLC. M I and M II were found
      in urine and M I was found in brain only. Furthermore, the ratio of radioactive M
      I to proptype drug was 1:1 in rat brain within 1 h following i.g. 3H-NBP. So, M I
      and M II were supposed to be the two main in vivo metabolites of NBP and M I
      might be an active metabolite.

PMID- 11596287
TI  - [Antitumor activity of the clavam peptide antibiotic G0069A].
AB  - Antibiotic G0069A, produced by a Streptomyces strain isolated from a soil sample
      collected in Yunnan Province, China, has been verified as a clavam peptide.
      Determined by MTT assay, G0069A showed highly potent cytotoxicity to cancer cells
      with multidrug resistance. The IC50 values of G0069A to KB and KB/VCR cells were
      0.60 and 0.46 mumol.L-1, and to MCF-7 and MCF-7/ADM cells were 1.4 and 1.2
      mumol.L-1, respectively. G0069A displayed equally potent cytotoxicity to the
      parent cell lines and their resistant sublines. When administered by i.v. or i.p.
      route at tolerable doses, G0069A exhibited markedly inhibitory effect on the
      growth of sarcoma 180 and hepatoma 22 in mice. At dose level of 3 mg.kg-1, i.v.,
      x3, sarcoma 180 and hepatoma 22 were suppressed by 87%(P < 0.01) and 72%(P <
      0.01), respectively. The results indicate that G0069A is a beta-lactam antibiotic
      showing antitumor activity.

PMID- 11596288
TI  - [In vivo and in vitro metabolism of tricyclopinate hydrochloride in the rat].
AB  - The metabolism of tricyclopinate hydrochloride(TCPN), a new anticholinergic
      agent, was studied by in situ perfused rat liver preparation. Two metabolites
      were isolated by HPLC. Metabolite I was identified as an N-demethylation product,
      while metabolite II was shown to be an arylhydroxylation product. Metabolite I
      and metabolite II were also isolated from the urine of the rat given TCPN i.g.
      This result shows that the two metabolites from the perfused rat liver are just
      the final metabolites produced in vivo. The metabolites in rat liver microsomes
      were also identified as those just described. These results suggest that the
      biotransformation reaction of TCPN is mainly catalyzed by the enzyme in rat liver
      microsomes. The results of experiment on receptor activity indicate that the
      action potency with mAChR of metabolite I and metabolite II was only 1/20 and
      1/50, respectively, of that of TCPN.

PMID- 11596289
TI  - [Effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino) propane
      hydrochloride on proliferation of vascular smooth muscle cells and PDGF-B, bFGF,
      c-sis, c-myc in spontaneously hypertensive rat].
AB  - In order to determine the effects of 1-(2, 6-dimethylphenoxy)-2-(3, 4
      dimethoxyphenylethylamino) propane hydrochloride(DDPH) on proliferation of
      vascular smooth muscle cells(VSMC), growth factor PDGF-B, bFGF and expression of
      oncogene c-sis and c-myc in spontaneously hypertensive rat(SHR), 3H-thymidine(3H
      TdR) incorporation, electronic microscopy, immunohistochemistry and in situ
      hybridization assays were used. The results showed that after DDPH administration
      (50 mg i.g. q.d. x8 wk to SHR), morphological change of VSMC was antagonized,
      blood pressure and 3H-TdR incorporation were significantly reduced. Furthermore,
      DDPH was shown to reverse the enhanced antigen PDGF-B and bFGF and reverse the
      reduced expression of oncogene c-sis and c-myc in SHR. These results suggest that
      DDPH may inhibit VSMC proliferation in SHR, which may be relevant to the
      molecular biological mechanism of growth factors and oncogene control.

PMID- 11596290
TI  - [Inhibitory effect of 2-(N-acetyl-methyl amino)-3',4'-methylenedioxyacetyl
      aminophene(SY-640) on covalent binding of carcinogenic benzo(a)pyrene with mouse
      hepatocyte nuclear DNA].
AB  - Many carcinogens must be first transformed into electrophilic ultimate
      carcinogens via metabolic activation in liver microsomes before covalent binding
      to nucleophilic center of DNA. SY-640 is a synthetic compound with
      hepatoprotective activity. Results of the present study indicate that the
      covalent binding of 3H-benzo(a)pyrine to mouse hepatocyte nuclear DNA in vitro
      and in vivo was markedly inhibited by SY-640. Further studies found that the
      liver microsomal cytochrome P-450 content and aminopyrine demethylase activity
      were significantly increased in mice treated with SY-640 (150 mg.kg-1 p.o.) once
      daily for three days, while the hepatic microsomal aminopyrine demethylase
      activity was obviously inhibited two hours after oral administration of SY-640
      150 mg.kg-1 in mice. The aminopyrine demethylase activity of liver microsomes
      from normal, PB- and 3-MC-treated mice was also significantly inhibited by the
      addition of SY-640 in vitro. When SY-640 was incubated with NADPH-reduced mouse
      liver microsomes, a metabolic-intermediate(MI) complex at 457 nm was formed. The
      effects of SY-640 on cytochrome P-450 and its formation of MI complex with
      cytochrome P-450 may partially explain why SY-640 could inhibit covalent-binding
      of BP to mouse hepatocyte DNA in vitro.

PMID- 11596292
TI  - [Studies on the synthesis of dl-ligustiphenol and its analogues].
AB  - S-( -- )-Ligustiphenol is a new sesquiterpene with anti-inflammatory and
      immunosuppressive activities.  In order to study its pharmacological activities,
      the total synthesis of its racemat was carried out by a six-step reaction
      sequence including bromination of aldehyde, iodination of m - cresol, protection
      of phenolic hydroxyl, Grignard reaction, Aldol condensation, etc.  The target
      compound was characterized by comparing its 1(H)-NMR, MS and IR spectra with
      natural ( -- )-ligustiphenol.  In order to study the structure-activity
      relationships of ligustiphenol, it five analogues were designed and synthesized. 
      The pharmacological screening of these analogues has been performed.

PMID- 11596291
TI  - [Use of monoclonal antibody-pinyangmycin conjugate in experimental regional
      targeting therapy of tumor].
AB  - McAb 3A5, a rat monoclonal antibody, was linked to pingyangmycin (PYM), an
      antitumor antibiotic identical to bleomycin A5 currently in clinical use,
      employing Dextran T-40 as an intermediate agent. The 3A5-PYM conjugate retained
      complete immunoreactivity of McAb 3A5. Determined by clonogenic assay with colon
      cancer HT-29 cells, the IC50 values for 3A5-PYM conjugate and free PYM were 0.6
      mumol.L-1 and 10.2 mumol.L-1, respectively. Hepatoma H22 ascites was transplanted
      into the peritoneal or thoracic cavity of mice. On the next day, 3A5-PYM or PYM,
      were injected into the cavity. Therapeutic effect was evaluated on the survival
      time of mice. For intraperitoneal tumor, the ILS(%) values were 238% for 3A5-PYM
      and 40% for PYM. For intrapleural tumor, the ILS(%) values were 384% for 3A5-PYM
      and 66% for PYM. Murine hepatoma H22 was transplanted s.c. into mice and 3A5-PYM
      conjugate or free PYM were injected peritumorally. As determined by antimicrobial
      assay, the administration of 3A5-PYM showed higher concentration and longer
      retention time in the tumor than that of free PYM. Tumor fragments of human colon
      cancer HT-29 were transplanted s.c. into nude mice. Then 3A5-PYM or PYM was
      injected i.v., i.p. or pt (peritumorally) 3 days after inoculation, twice a week,
      with a total of 7 injections. Tumor growth inhibition was evaluated 4 weeks
      later. The inhibition rates on the growth of colon cancer xenografts were as
      follows: (1) for i.v. route, 58% by PYM, 79% by 3A5-PYM; (2) for i.p. route, 52%
      by PYM, 61% by 3A5-PYM; and (3) for pt route, 73% by PYM, 96% by 3A5-PYM. These
      results indicate that 3A5-PYM conjugate is highly effective against targeted
      human cancer xenograft and mouse tumor when administered peritumorlly or
      intracavitarily.

PMID- 11596293
TI  - [The isolation and identification of four new 2, 2-dimethylchromenes].
AB  - Four new 2, 2-dimethylchromenes named leptol B (I), ethylleptol B (II),
      methylleptol B (III), leptene B (IV), along with a known chromene-methylevodionol
      (V) have been isolated from the aerial parts of Evodia lepta. Their structures
      were elucidated by spectroscopic analysis and chemical techniques.

PMID- 11596294
TI  - [Oleanolic acid saponins from the root bark of Aralia taibaiensis].
AB  - Five oleanolic acid saponins were isolated from the root bark of Aralia
      taibaiensis Z.Z. Wang et H.C. Zheng. By spectroscopic and chemical methods, they
      were identified as araloside A (1), 3-O-[alpha-L-arabinofuranosyl(1-->4)-6'-O-n
      butyl-beta-D- glucuronopyranosyl]-oleanolic acid-28-O-beta-D-glucopyranoside (2),
      3-O-[alpha-L-arabinofuranosyl(1-->4)-6'-O-ethyl-beta-D- glucuronopyra-nosyl]
      oleanolic acid-28-O-beta-D-glucopyranoside (3), stipuleanoside R2(4) and 3-O
      (beta-D-glucopyranosyl(1-->3) [alpha-L-arabinofuranosyl(1-->4)]-6'-O-ethyl-beta-D
      glucuronopyranosyl)-oleanolic acid-28-O-beta-D-glucopyranoside (5). Saponin 1
      and 4 were isolated from the title plant for the first time. 2, 3 and 5 are new
      compounds and named taibaienoside I, taibaienoside II and taibaienoside III,
      respectively.

PMID- 11596295
TI  - [Studies on the voltammetric behaviour of barbaloin and its application].
AB  - In 0.1 mol.L-1 H2SO4 solution, a well-defined reduction wave of barbaloin was
      obtained by single-sweep osciflopolarography. The peak potential was shown to be 
      0.75 V (vs SCE). The peak current is proportional to the concentration of
      barbaloin over the range of 2.0 x 10(-7)-6.0 x 10(-6) mol.L-1. The detection
      limit is 2.0 x 10(-7) mol.L-1. The voltammetric behaviour of the system was
      studied by linear sweep and cyclic voltammetry. The adsorption coefficient beta
      was 1.91 x 10(5). The interaction factor alpha was 1.12. The system is a
      reversible adsorption wave.

PMID- 11596296
TI  - [Simultaneous determination of tyrosine and tryptophan in amino acid injection,
      animal and plant extracts by polarization spectrofluorimetry].
AB  - A new method for the simultaneous determination of tyrosine and tryptophan by
      polarization spectrofluorimetry has been developed. The interference of
      phenylalanine and light scattering of solvent were eliminated by using vertically
      crossed polarizers. The overlapping of fluorescence spectra of the two amino
      acids was solved with filters. The linear ranges of determination were 0.02-12.0
      mg.L-1(tyrosine) and 0.01-2.50 mg.L-1(tryptophan). The mean recoveries of
      tyrosine and tryptophan in samples were 95.4% and 101.7% (in amino acid
      injection). 99.2% and 100.0% (in wild jujube kernel), 95.3% and 97.2% (in shrimp
      shell) respectively. The proposed method has been used to determine tyrosine and
      tryptophan in amino acid injection, extracts of wild jujube kernel and shrimp
      shells with satisfactory results.

PMID- 11596297
TI  - [Synthesis of carbonyl chlorides substituted with aromatic dense-ring].
AB  - Carbonyl chlorides substituted with aromatic dense-ring are chemically active and
      their fluorescent quantum yields are usually high and they may be used as
      fluorescent probes for detection of many compounds.  Studies on their synthesis
      and structure activity relationship are very important in the micro-or supermicro
      detection of drugs and toxicants containing hydroxy groups.  Therefore,  the
      probes may find wide application in the chemical engineering and pharmaceutical
      industry.  Three new fluorescent probes: Beta-(9-anthracene) acrylonyl chloride,
      Beta-(9-anthracene) propionyl chloride and Beta-( 1-pyrene ) acrylonyl chloride
      were synthesized by the reaction between the corresponding  acid and thionyl
      chloride. 1-Prenecarboxaldehyde synthesized by using pyrene and N-formyl-N
      methylaniline with phosphorus oxychloride as catalyst, was allowed to react with
      malonic acid to produce Beta-(1-pyrene) acrylic acid for the last-mentioned acid
      chloride.

PMID- 11596298
TI  - [Triterpene acids from the barks of Illicium difengpi].
AB  - Four compounds were isolated from the traditional Chinese medicine "Difengpi",
      barks of Illicium difengpi K.I.B. et K.I.M. They were identified as 3 beta-O
      acetyl-mangiferolic acid (I), mangiferonic acid (II), mangiferolic acid (III) and
      butulinic acid (IV) by physico-chemical constants and spectral analyses (UV, IR,
      EIMS, 1HNMR, 13CNMR, NOEDE and 2D NMR). Compound I is a new compound. These
      triterpene acids (I-IV) were isolated from Illicium genus for the first time.

PMID- 11596299
TI  - [Comparison of bioavailability between nimotop and nimodipine tablet].
AB  - A new analytical method was established for determining plasma level of
      nimodipine using HPLC and its application to determine the bioavailability of
      nimodipine. Experiments were performed on a Waters Model Baseline 810 System
      instrument. A 3.9 mm x 200 mm stainless steel column was packed with YWG-C18(10
      microns) as the stationary phase. The mobile phase was a mixture solution of
      methanol--water (60/40, v/v) with 1.00 ml.min-1 at 35 degrees C. The detector was
      set at 358 nm. The plasma samples were extracted with ether--n-hexane (1:1).
      Calibration curve was linear (gamma = 0.9999) in the concentration range of 5-300
      ng.ml-1. The within-day and between-day precision (RSD) were less than 3% and 5%,
      respectively, with average recoveries of 97.67%-102.3%. The study on
      bioavailability of numodipine between tablet A (made in China) and nimotop
      (Bayer, Germany) was carried out in 8 volunteers at the oral dose of 120 mg by
      cross-over method. Two-compartment open model was suitable for describing the
      disposition of nimodipine. The main pharmacokinetic parameters were shown in Tab
      1 and mean plasma concentration--time curve of nimodipine was shown in Fig 1. The
      results indicate that tablet A exhibited a lower bioavailability (relative to
      nimotop). We suggest that the product tablet A must be improved in formula and
      technology.

PMID- 11596300
TI  - [Advances in the studies of saponins from Aralia].

PMID- 11596301
TI  - [Effects of Tremella polysaccharide on cytoplasmic free calcium concentration in
      murine splenocytes].
AB  - Effects of Tremella polysaccharides (TP) isolated from Tremella fuciformis Berk.
      on the cytoplasmic free calcium concentration in murine splenocytes were observed
      using Fura-2, a fluorescence indicator, technique. TP increased the cytoplasmic
      free calcium concentration of Fura-2-loaded murine splenocytes in a concentration
      dependent manner and showed synergetic effect with Con A. No effect was found in
      the release of intracellular calcium without extracellular calcium. Verapamil (10
      micrograms.ml-1), a calcium channel blocker, was shown to inhibit the effect of
      TP on cytoplasmic free calcium, indicating that TP can affect the influx of
      extracellular calcium.

PMID- 11596302
TI  - [Wild-type p53 stimulates vincristine-induced apoptosis].
AB  - Recent studies indicate that wild-type p53 can trigger cell apoptosis induced by
      many chemotherapeutic agents which induce DNA damage or cause disruptions of DNA
      metabolism, such as ADM, 5-FU, VP-16 and radiation. We introduced the wild-type
      p53 gene into a MDR cell line KBV200 in which the endogenous p53 was found to be
      rearranged. By G418 selection and Northern blot analysis, a G418-resistant clone
      named KBV200-p53 was obtained which continuously expressed the exogenous wild
      type p53 mRNA. After treatment with Vincristine(VCR), the wild type p53
      expression cells presented typical morphology characteristic of apoptosis
      analysed under electron and fluorescence microscopes. Flow cytometer analysis
      showed that the KBV200-p53 cells were more readily undergo apoptosis than their
      parental cells KBV200. After treatment with VCR 600 nmol.L-1 for 24 h, the
      apoptotic percentage of KBV200-p53 and KBV200 cells was about 42.4% and 8.4%,
      respectively. This result indicates that wild-type p53 stimulates VCR-induced
      apoptosis in KBV200 cells.

PMID- 11596303
TI  - [Effect of SR-140333, a tachykinin NK-1 antagonist, on antigen-induced airway
      hyperresponsiveness in sensitized rats].
AB  - In the present study, the effects of SR-140333, ((S)-1-(2-[3,4-dichlorophenyl)-1
      (3-isopropoxyphenylacetyl)piperidin- 3yl]ethyl)-4-phenyl-1
      azoniabicyclo[2.2.2]octane.chloride), a nonpeptide antagonist for tachykinin NK-1
      receptor, on the antigen-induced airway response to methacholine (MCh) aerosol
      and airway inflammation in sensitized SD rats were investigated. The baseline
      respiratory frequencies, tachypnea response to methacholine(MCh), the -log PC30
      values of MCh and the leukocyte counts in bronchoalveolar lavage significantly
      increased after inhalation of 1% oval albumin(OA) aerosol. SR-140333 (152 nmol.kg
      1, i.p.) or dexamethasone(368 nmol.kg-1, i.p.), bid x 3 d inhibited these
      responses. SR-140333 at a low dose of 0.01 mg.kg-1 showed an incomplete
      inhibition. From these results, we conclude that antigen challenge causes airway
      hyperresponsiveness and airway inflammation and that tachykinin NK-1 receptor
      antagonist inhibits these responses.

PMID- 11596304
TI  - [The effects of gossypol on rat luteal cells, human decidual cells and
      cytotrophoblasts].
AB  - The direct effects of gossypol on the serum-free primary cultures of rat luteal
      cells and cytotrophoblasts were observed. The results indicate that: (1) Gossypol
      affected the viability of the cultured rat luteal cells, LD50: 1.6 (0.4-2.9)
      micrograms.ml-1. (2) The basal secretions of progesterone were significantly
      inhibited at low and high concentrations. The activities of 3 beta-HSD, adenyl
      cyclase and hCG-stimulated progesterone production were inhibited by higher
      concentrations of gossypol. (3) Gossypol damaged cultured human decidual cells
      and cytotrophoblasts, the LD50 were 3.5(0.4-6.6) micrograms.ml-1 and 4.1(0.6-7.6)
      micrograms.ml-1, respectively. These results suggest that the luteolytic effect
      is the main mechanism of action for the termination of early pregnancy by
      gossypol, while the direct damaging effects on decidual cells and
      cytotrophoblasts may also play a role in the termination of early pregnancy.

PMID- 11596305
TI  - [Effects of praeruptorin C on cardiac dysfunction, myocardial compliance and
      collagen content in renovascular hypertensive rats].
AB  - The effects of praeruptorin C (Pra-C) on cardiac dysfunction, myocardial
      compliance, and collagen content in renovascular hypertensive rats have been
      studied. In rats with left ventricular hypertrophy (LVH), the ratio of cardiac
      flow (CF)/heart wet weight (HWW) and cardiac output (CO)/HWW decreased by 20.1%
      and 35.5%; LVSP and -dp/dtmax decreased by 19.4% and 42.1%, while LVEDP and T
      value were increased by 186.4% and 226%. The left ventricular diastolic pressure
      volume (P-V) curve was shifted to the left and down ward compared with that of
      sham-operated rats. The hydroxyproline content was 5.93 +/- 0.82 mg.g-1 dry
      weight in the left ventricular myocardial tissue of rats with LVH which was
      higher than that of sham-operated rats(e.g. 4.01 +/- 0.47 mg.g-1). The content
      did not change in the right ventricular myocardium. After treated with Pra-C for
      nine weeks, the CF/HWW and CO/HWW increased by 31.3% and 25.1%, the LVSP and 
      dp/dtmax increased by 16.7% and 27.8%. The LVEDP and T value was reduced by 34.9%
      and 36.5%, respectively, compared with those of LVH. The P-V curves of these rats
      were shifted to the right and in the up-ward direction. The hydroxyproline
      content was 4.52 +/- 0.3 mg.g-1 dry weight in the left ventricular tissue. These
      results indicate that Pra-C improved the cardiac contractility and relaxation by
      increasing the coronary flow and cardiac output, and decreasing the collagen
      content in the ventricular myocardium.

PMID- 11596306
TI  - [Effects of tyrosine alone and tyrosine in combination with RU486 on early
      pregnancy in mice and the mechanism of action].
AB  - Treatment with tyrosine at the dosage of 85 mg.kg-1 on day 6-8 of gestation did
      not have significant effect to terminate early pregnancy in mice. Tyrosine
      combined with RU486 was shown to have a synergistic effect to terminate early
      pregnancy. Tyrosine 170 mg.kg-1 on day 6-10 of gestation significantly decreased
      the concentration of serum progesterone in early pregnant mice. Further study
      with luteal cells in rats showed that tyrosine 50 micrograms.ml-1 inhibited hCG
      induced progesterone production when used alone, and inhibited basal production
      when used together with (+) PG05. These results suggest that the inhibiting
      effect of tyrosine on steroidogenesis may contribute to the termination of early
      pregnancy.

PMID- 11596307
TI  - Regulation of water channel gene (AQP-CHIP) expression by estradiol and anordiol
      in rat uterus.
AB  - In the present studies, we observed the regulation of water channel gene (AQP
      CHIP) expression by estradiol (E2) and anordiol, an antiestrogen with agonist
      activity, in immature female rat uterus. Antisense and sense oligonucleotide
      primers corresponding to the consensus sequences of two rats AQP-CHIP water
      channels were synthesized and used to amplify a cDNA fragment that was reverse
      transcripted from rat uterine total RNA preparation. E2 administered as a single
      dose of 40 micrograms.kg-1 to immature female rats induced a significant increase
      in AQP-CHIP mRNA expression 9 h after treatment. The lowest effective doses of E2
      and anordiol were 40 and 50 micrograms.kg-1, respectively. The stimulatory effect
      of anordiol was more pronounced than that of E2. The present results suggest that
      AQP-CHIP water channel gene expression may be involved in E2- and anordiol
      mediated water imbibition and luminal fluid production in the uterus.

PMID- 11596309
TI  - [Study on flavonoids in seeds of Hovenia dulcis].
AB  - Four flavanoids were isolated from the seed of Hovenia dulcis Thunb. On the basis
      of physicochemical properties and spectroscopic analysis, their structures were
      identified as dihydrokaempferol (I), quercetin (II), (+)-3,3',5',5,7
      pentahydroflavanone (III) and (+)-dihydromyricetin (IV). Among them, III was a
      new compound; I and IV were first isolated from genus Hovenis.

PMID- 11596308
TI  - [Comparative molecular field analysis (CoMFA) of allylamine antimycotics].
AB  - Active analog approach has been applied to determine the pharmacophoric
      conformations of the allylamine antimycotics. Comparative molecular field
      analysis (CoMFA) has been used to establish 3D-QSAR of 48 allylamine antimycotics
      against six common human pathogenic fungi. Two different alignment rules were
      compared in the meantime. Five new synthetic compounds have been successfully
      employed to examine the predictive abilities of the CoMFA models against
      Trichophyton mentagrophytes and Aspergillus fumigatus.

PMID- 11596310
TI  - [Studies on isolation, purification and structure of polysaccharide RHG from
      Hedysarum polybotrys Hand.-Mazz].
AB  - A water-soluble polysaccharide, RHG, was isolated from the roots of Hedysarum
      polybotrys Hand.-Mazz. It was shown to be homogeneous by electrophoresis and gel
      filtration. Its average molecular weight was estimated to be 1.4 x 10(4).
      Methylation analysis, periodate oxidation, Smith degradation, IR, NMR and KI-I2
      reaction showed that RHG is a (1-4) linked alpha-D-glucan to which the glucosyl
      side chains are attached at O-6 of the glucosyl residues of the main chain.

PMID- 11596311
TI  - [HPLC determination of five caffeine metabolites].
AB  - An HPLC method for the determination of caffeine metabolites in urine was
      established. Shim Pack CLC-ODS column (5 microns) was eluted with the mobile
      phase of methanol--acetonitrile--0.05% acetic acid = 12:1:87 (v/v) at a flow rate
      of 1.2 ml.min-1, and the ultraviolet absorbance was monitored at 280 nm. The 13
      caffeine metabolites and caffeine were well separated and the concentrations of
      the five metabolites, AFMU, 1U, 1X, 17U, and 17X, were determined. The recoveries
      of the five metabolites were above 87%, the inter- and intra-day variations were
      less than 3%. The concentrations of the five metabolites in 120 volunteers were
      determined. The ratios of the metabolites were employed for the assessment of
      CYP1A2, NAT, and XO enzymes successfully.

PMID- 11596312
TI  - [Separation of pharmaceutical enantiomers on column and thin-layer plate of
      cellulose triacetate].
AB  - Microcrystalline cellulose triacetate (CTA) was prepared by heterogeneous
      acetylation of microcrystalline cellulose and used as liquid chromatographic
      chiral stationary phase and chiral thin layer plate to separate pharmaceutical
      enantiomers. The racemic Troegor's base, mathaqualone, chlormezanone and
      chloroquine were separated on the CTA chiral column and on the CTA chiral plate.
      95% ethanol and the mixtures of 95% ethanol and water with different ratio and
      different pH values were used as mobile phase. The influences of eluent
      composition, pH and temperature on the chiral separation were discussed. The
      experimental results indicate that the CTA chiral plate was more sensitive to
      eluent composition and pH than chiral column possibly because the chiral
      adsorbent was not swollen on the plate.

PMID- 11596314
TI  - [Determination of sinomenine HCl in serum and urine by HPLC and its
      pharmacokinetics in normal volunteers].
AB  - A RP-HPLC method was developed to determine the concentrations of sinomenine HCl
      in serum and urine and its pharmacokinetics was studied in healthy volunteers.
      C18H37 column was eluted with the mobile phase of acetonitrile--0.01 mol.L-1
      sodium phosphate monobasic--N, N, N', N'-tetramethylenediamine (46:54:0.22 v/v,
      pH 6.9) and the ultraviolet absorbance was monitored at 263 nm. Triazolan was
      used as internal standard. The calibration curves were linear in the range of 6
      480 ng.ml-1 in serum and 0.06-3 micrograms.ml-1 in urine, with mean recoveries of
      75.46% and 91.38% respectively. The lowest detectable limits were 4 ng.ml-1 in
      serum and 40 ng.ml-1 in urine and the RSD for the intra-day and inter-day were
      less than 5%. A single oral dose of 80 mg sinomenine HCl tablet was given to 8
      healthy male volunteers. The concentrations of sinomenine HCl in serum and urine
      were determined. The serum concentration--time curve was found to fit a two
      compartment open model with first order elimination. The pharmacokinetic
      parameters were: T1/2 alpha 0.791 +/- 0.491 h, T1/2 beta 9.397 +/- 2.425 h, Tmax
      1.040 +/- 0.274 h, Cmax 246.604 +/- 71.165 ng.ml-1, AUC 2651.158 +/- 1039.050
      ng.h.ml-1, CL 0.033 +/- 0.010 ng.ml-1.

PMID- 11596313
TI  - [Determination of adenosine and thymidine in Fritillaria bulbs by dual wavelength
      ultraviolet spectrophotometry].
AB  - A convenient method for the quantitative analysis of adenosine and thymidine in
      Fritillaria bulbs was developed by means of dual wavelength ultraviolet
      spectrophotometry. This method has good linear relationship and the interrelated
      coefficient of standard curve for adenosine and thymidine were all found to be
      0.9999. The methanol extracts of four species of Fritillaria have been analyzed
      with this method. The results show that the the bulbs of four species contain
      different quantities of adenosine and thymidine, which indicates that the
      nucleosides may be responsible for the anti-coagulation activity of Fritillaria.

PMID- 11596315
TI  - [HPLC determination of six flavonoid constituents in Ginkgo biloba leaves].
AB  - Six flavonoid constituents (quercetin, isorhamnetin, kaempferol, bilobetin,
      ginkgetin and sciadopitysin) were isolated from Ginkgo biloba leaves and
      determined by reversed phase HPLC using salvianolic acid B as internal standard.
      The column employed was Zorbax ODS (150 mm x 4 mm ID, 5 microns). The mobile
      phase consisted of solvent A (methanol) and solvent B [tetrahydrofuran--water-
      formic acid (34:65:1)] for gradient elution. The flow rate was 1 ml.min-1 and
      detection was effected at 350 nm. This method is accurate, rapid and
      reproducible. Analytical data for various samples were given.

PMID- 11596316
TI  - [Stimulatory effect of sodium deoxycholate on alpha-ergocryptine productivity of
      Claviceps purpurea 94002 (EKPN94002)].
AB  - The stimulation of sodium deoxycholate (SDC) on alpha-ergocryptine production of
      Claviceps purpurea strain 94002 (EKPN94002) was investigated. Preliminary results
      indicated that SDC, as a stimulator and at appropriate concentrations, could
      obviously increase the extracellular and the total production levels of the ergot
      alkaloid. Satisfied results were obtained when 6.0 mg.L-1 of SDC was present in
      the seed and fermentation media. The possible mechanism was discussed.

PMID- 11596317
TI  - [Isolation and identification of ecliptasaponin D from Eclipta alba (L.) Hassk].
AB  - A new triterpenoid glucoside ecliptasaponin D was isolated from Eclipta alba (L.)
      Hassk. Its structure was deduced as 3 beta, 16 beta-dihydroxy olean-12-ene-28-oic
      acid-3 beta-O-beta-D-glucopyranoside, based on spectral analysis and chemical
      evidences as well as results of hydrolysis.

PMID- 11596318
TI  - [Determination of docosahexenoic acid in human serum by capillary gas
      chromatography].
AB  - A reliable CGC method was developed for the determination of docosahexenoic acid
      (DHA) in human serum. The serum sample was acidified by adding two drops of 4.5
      mol.L-1 H2SO4, and DHA was extracted from serum using ethyl acetate. The extract
      was evaporated to dryness under nitrogen stream. To each residue, 1 ml 1.3 mol.L
      1 methanolic hydrogen chloride solution was added and the mixture was allowed to
      stand for 30 min in 60 degrees C water bath. After derivatization, the mixture
      was extracted with 1 ml of n-hexane. The solvent was evaporated under a stream of
      nitrogen to dryness and the residue was dissolved in 30 microliters n-hexane and
      subjected to capillary GC, which was equipped with a fused silica capillary
      column (26.3 m x 0.25 mm ID) coated with FFAP (free fatty acid phase, 0.1 micron
      film thickness). Tricosanoic acid was used as an internal standard. The retention
      time of DHA-M and internal standard was 23.41 min and 20.79 min, respectively.
      The minimum detection concentration of DHA in serum was 40 ng.ml-1 with a serum
      volume of 200 microliters and S/N value of 2. A good linear relationship between
      the peak area ratios and concentrations was found at the DHA concentrations
      ranging from 25 to 200 micrograms.ml-1. The within-day and between-day precision
      was 5% and 9%, respectively.

PMID- 11596319
TI  - [Cerebral glutamate/GABA system to regulate learning and memory].

PMID- 11596320
TI  - [Compared study on Fura-2/AM assay and MTT assay for screening multidrug
      resistant modulators].
AB  - To explore the difference of screening results of reversing multidrug resistance
      (MDR) by modulators between Fura-2/AM assay and MTT assay, 25 compounds which
      have active structure were studied for MDR reversal activity with both methods.
      The fold of MDR reversal was shown to have remarkable relation with the amount of
      Fura-2 accumulation (Y = -3.66 + 17.5X, gamma = 0.86, P < 0.01). On the other
      hand, Fura-2/AM assay has several advantages as compared with MTT assay. Fura
      2/AM assay needs shorter time (4 h) than MTT assay (96 h), and the MTT assay
      needs more steps than the Fura-2/AM assay. Furthermore, Fura-2/AM assay was more
      reliable than MTT assay for screening MDR modulators because MTT assay was
      dependent on the viable cells, while Fura-2/AM assay was dependent on the
      function of P-gp. The results suggest that Fura-2/AM assay may replace MTT assay
      in the screening of MDR modulators on a large scale.

PMID- 11596321
TI  - [Study on the anti-apoptotic mechanism of ginsenoside Rg1 in cultured cortical
      neurons].
AB  - Ginsenoside Rg1 is an active principle isolated from Panax ginseng CA Meyer.
      Primary neuronal culture was performed with different concentrations of Rg1. On
      the 14th day, the culture was changed to serum-free medium. On the 16th day,
      neurons were harvested and assayed under microscope and fluorescence microscope.
      The result showed that serum withdrawal from the medium induced apoptosis in
      primary cultured cortical neurons. Rg1 (1, 10 mumol.L-1) was shown to inhibit
      apoptosis and protect neurons against injury. Membrane fluidity was measured
      using fluorescence spectrophotometer in five groups of cultured cortical neurons:
      control (complete medium), apoptosis (serum-free medium), Rg1 0.1 mumol.L-1, Rg1
      1 mumol.L-1 and Rg1 10 mumol.L-1. Neurons were isolated enzymatically and loaded
      with the fluorescent dye, DPH (1, 6-diphenyl-1,3,5-hexatriene). Membrane fluidity
      in control neurons (eta 1.2928 +/- 0.1426) was shown to be significantly higher
      than that in apoptosis cells (eta 2.9277 +/- 0.2004). The membrane fluidity of
      neurons treated with Rg1 (0.1, 1, 10 mumol.L-1) increased significantly (eta
      2.9172 +/- 0.1604, 2.4731 +/- 0.2187, 1.6436 +/- 0.1483). These findings indicate
      a substantial alteration of membrane fluidity with neuronal apoptosis. Increment
      of membrane fluidity provides an aspect of elucidating the mechanism of Rg1's
      anti-apoptosis function.

PMID- 11596323
TI  - [Studies on the chemical constituents of Annona muricata].
AB  - Annonaceous acetogenin (or polyketide) is a kind of potential antineoplastic
      agents from Annonaceae plants. Two new acetogenins, Muricatalicin (I) and
      muricatalin (VI), a mesitoate of a new acetogenin, annonacin-B mesitoate (Vb),
      and three known acetogenins, annonacin (II), annonacin-A (III) and annonacin-10
      one (IV) have been isolated from Annona muricata L. The structures and relative
      stereochemistry of I, VI and Vb were elucidated on the basis of spectral analysis
      and examination of their acetates and/or mesitoate.

PMID- 11596322
TI  - [Pharmacokinetic-pharmacodynamic modeling of metoprolol enantiomers in the dog].
AB  - The PK-PD model of (+)-Met and (-)-Met was studied in anesthetized dogs. The
      plasma drug concentration-time profiles were most adequately described by two
      compartment model. Significant differences of Vd/F, CLs/F and AUC between (+)-Met
      and (-)-Met were observed. The peak times of plasma (+)-Met and (-)-Met
      concentration in dogs were 24 +/- 5 and 30 +/- 5 min, respectively. But the peak
      times of drug inhibitory effects on Vmax, dp/dtmax, LVSP, SBP and HR were about
      90-120 min, showing the hysteresis loops. When using the effect compartment
      model, the counterclockwise hysteresis collapsed and the relationships between
      the effects and concentration in effect compartment were fit by using Sigmoid
      Emax model. The Ce50 values of inhibitory effects on Vmax, dp/dtmax and HR of (+)
      Met were 250 +/- 80, 450 +/- 210, 520 +/- 210 micrograms.L-1 and those of (-)-Met
      were 70 +/- 30, 70 +/- 40 and 82 +/- 27 micrograms.L-1, respectively. Significant
      differences of Ce50 of (+)-Met and (-)-Met were found. The values of Ce50+/Ce50-
      were 3.7, 6.8 and 6.3, indicating that the inhibitory effects on Vmax, dp/dtmax
      and HR of (-)-Met were stronger than those of (+)-Met in dogs.

PMID- 11596324
TI  - [Studies on polysaccharide from Akebia trifoliate (I)].
AB  - Crude polysaccharide ATB was extracted from the stems of Akebia trifoliate with
      5% NaOH. It was then subjected to DEAE-Cellulose column chromatography and
      purified by Sephadex G-200 chromatography. Finally, a pure polysaccharide ATBB-2
      was obtained. The molecular weight of ATBB-2 was estimated to be 2.3 x 10(5). By
      total acid hydrolysis, the analytical results indicated that ATBB-2 is composed
      of Rha, Ara, Xyl, Gal, Glc and GalA in a molar ratio of
      1.22:1.00:1.10:0.85:0.24:0.82. Methylation analysis, periodate oxidation
      analysis, Smith degradation, partial acid hydrolysis, 1H and 13CNMR showed that
      ATBB-2 is a highly branched molecule without a main chain.

PMID- 11596325
TI  - [Isolation and identification of two new secoiridoids of water-soluble chemical
      constituents from the fruits of Ligustrum lucidum Ait].
AB  - Two new secoiridoids named as specnuezhenide (I) and nuezhengalaside (II) were
      isolated from the water-soluble part of dry fruits of Ligustrum lucidum Ait.
      Their structures were established on the basis of chemical analysis and spectral
      data (UV, IR, 1H-NMR, NOEDS, HOMO-DEC, 13C-NMR, DEPT and MS).

PMID- 11596326
TI  - [Studies on the ganoderic acid, a new constituents from the fruiting body of
      Ganoderma lucidum (Fr.) Karst].
AB  - Three compounds have been isolated from the dichloromethane soluble fraction of
      the fruiting body of Ganoderma lucidum (Fr.) Karst. On basis of spectral analyses
      (UV, IR, MS, 1HNMR, 13CNMR and 2D-NMR), they were identified as 3, 7-dioxo
      lanosta-8, 24(E)-dien-26-oic acid (I), 7 beta-15 alpha-dihydroxy-3, 11, 23-trioxo
      5 alpha-lanost-8-en-26-oic acid (II) and 3 beta, 7 beta, 15 alpha-trihydroxy-11,
      23-dioxo-5 alpha-lanosta-8-en-26-oic acid (III). Compound I is a new compound
      named ganoderic acid DM.

PMID- 11596327
TI  - [Studies on the flavonoids from Dendranthema lavandulifolium].
AB  - From the whole plant of Dendranthema lavandulifolium, two flavonoides (I, II) and
      two flavone glycosides (III, IV) were isolated. They were identified as luteolin
      (I), apigenin (II), 5-hydroxy-4'-methoxy-flavone-7-O-alpha-L-rhamnopyranosyl(1-
      >6)-beta- D-glucopyranosyl (acaciin III) and 5-hydroxy-4'-methoxy-flavone-7-O
      alpha-L-rhamnopyranosyl (1-->6) [2-O-acetyl-beta-D-glucopyranosyl(1-->2)]-beta-D
      glucopyranoside (IV) by means of IR, UV, 1H-NMR, 13C-NMR, EI-MS, HRFAB, etc.
      Among these four compounds, I, II were isolated for the first time from this
      plant, IV is a new compound.

PMID- 11596328
TI  - [Studies on chemical constituents of Kadsura Longepedunculata].
AB  - The chemical constituents of Kadsura Longepedunculata collected from Zhejiang
      province were studied. Six compounds were isolated and their structures were
      elucidated based on physical and spectral analysis. Among them, one is a new
      compound, which is named kadsulactone acid (I) and the others are kadsulactone
      (II), (+)-anwulignan (III), mesodihydroguaiaretic acid (IV), d-epidalbacin(V) and
      beta-sitosterol (VI).

PMID- 11596329
TI  - [Studies on octanol-water partition coefficient and nasal drug absorption].
AB  - In order to find out the quantitative relationship between physicochemical
      properties of drugs and their nasal absorption, diltiazem hydrochloride and
      paracetamol were selected as model drugs and their octanol-water partition
      coefficient was determined. In situ nasal recirculation method at different pH
      values was used to estimate the rate constant of nasal drug absorption in rats.
      Results showed that quantitative relationship existed between partition
      coefficient and nasal absorption constant, with correlation coefficient being
      0.9761(n = 9). Besides methods of partition coefficient determination, the in
      situ nasal recirculation manipulation was also improved.

PMID- 11596330
TI  - [A model atlas of the crude drug Radix Ophiopogonis in tri-dimensional computer
      reconstraction from their serial transections].
AB  - In this paper, the tri-dimensional computer reconstruction and animated display
      from the serial transections of the crude drugs Radix Ophiopogonis and Radix
      Liriopes have been achieved. Accordingly, some tri-dimensional image techniques
      and information for the computer aided teaching and identification of
      pharmacognosy have been offered.

PMID- 11596331
TI  - [Acetylsalvianolic acid A--a new thromboxane synthetase inhibitor].
AB  - With radio thin layer chromatography and autoradiogram, the effect of
      acetylsalvianolic acid A (ASAA) on 14C-arachidonic metabolism by platelets was
      studied in vitro. ASAA was found to enhance the formation of PGE2 and PGF2 alpha
      remarkably while inhibiting the formation of TXB2. However, it showed no effect
      on the formation of 12-HETE and arachidonic utility rate. Therefore, we deduce
      that ASAA may be a thromboxane synthetase inhibitor.

PMID- 11596332
TI  - [High performance liquid chromatographic method for the determination of
      ipriflavone in serum and its pharmacokinetic study in healthy volunteers].
AB  - A sensitive and rapid high performance liquid chromatographic method has been
      developed for the determination of ipriflavone in human serum. The average
      recovery of ipriflavone was 85% with relative standard deviation of 3.8%-5.4%.
      The calibration curve was linear in the range from 8 ng.ml-1 to 400 ng.ml-1 with
      gamma = 0.9981. The detection limit of the method was 3 ng.ml-1 (S/N > or = 3).
      The serum drug concentration-time curve exhibited a 2-compartment model and the
      mean T1/2 beta was 12.00 +/- 1.89 h (for ipriflavone made in Japan) and 9.05 +/-
      0.80 h (for ipriflavone made in China). The AUC0-->infinity of the two kinds of
      ipriflavone were 804.99 ng.h.ml-1 and 807.40 ng.h.ml-1, respectively. The
      relative bioavailability of ipriflavone made in China vs that made in Japan was
      1.003.

PMID- 11596333
TI  - [Isolation and structure determination of xanthone glycosides of Anemarrhena
      asphodeloides].
AB  - Xilingzhimu, the rhizomes of Anemarrhena asphodeloides Bunge (Liliaceae), has
      been prescribed as antipyretic, anti-inflammatory, diuretic and hypoglycemic
      agents in Chinese traditional medicine. In this paper, two xanthone glycosides I
      and II, were isolated from Xilingzhimu by conventional method. The structures of
      I and II were identified on the basis of chemical reactions and UV, IR, 1HNMR,
      13CNMR and DEPT. Compound I was identified as mangiferin and II is a new
      compound, named neomangiferin. Its structure is 7-O-beta-D-glucopyranosyl
      mangiferin.

PMID- 11596334
TI  - [Applications of high performance capillary electrophoresis in constituents
      analysis of Chinese traditional medicine].

PMID- 11596335
TI  - [Pyruvate carboxylase deficiency].

PMID- 11596336
TI  - [Pyruvate dehydrogenase complex deficiency].

PMID- 11596337
TI  - [Fumarase deficiency].

PMID- 11596338
TI  - [Alpha ketoglutarate dehydrogenase deficiency].

PMID- 11596339
TI  - [Aconitase deficiency].

PMID- 11596340
TI  - [Canavan disease (aspartoacylase deficiency)].

PMID- 11596341
TI  - [Myoadenylate deaminase deficiency].

PMID- 11596342
TI  - [Complex I (NADH-ubiquinone oxidoreductase) deficiency].

PMID- 11596343
TI  - [Complex II (succinate-ubiquinone reductase) deficiency].

PMID- 11596344
TI  - [Complex III (ubiquinone-cytochrome c reductase) deficiency].

PMID- 11596345
TI  - [Complex IV (cytochrome c oxidase) deficiency].

PMID- 11596346
TI  - [Myophosphorylase deficiency].

PMID- 11596347
TI  - [Complex V (ATP synthase) deficiency].

PMID- 11596348
TI  - [Classification of mitochondrial diseases according to the clinical phenotype].

PMID- 11596349
TI  - [MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like
      episodes)].

PMID- 11596350
TI  - [MERRF (myoclonus epilepsy associated with ragged-red fibers)].

PMID- 11596351
TI  - [Chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre syndrome
      (KSS)].

PMID- 11596352
TI  - [MELAS + KSS].

PMID- 11596353
TI  - [MERRF/MELAS overlap syndrome].

PMID- 11596354
TI  - [MNGIE (mitochondrial neurogastrointestinal encephalomyopathy)].

PMID- 11596355
TI  - [NARP (neurogenic muscle weakness, ataxia and retinitis pigmentosa)].

PMID- 11596356
TI  - [Luft disease].

PMID- 11596357
TI  - [Ekbom syndrome].

PMID- 11596358
TI  - [Phosphorylase b kinase deficiency].

PMID- 11596359
TI  - [ARCO (autosomal recessive cardiomyopathy and ophthalmoplegia)].

PMID- 11596360
TI  - [SANDO (sensory ataxic neuropathy, dysarthria, and ophthalmoplegia)].

PMID- 11596361
TI  - [Fatal infantile mitochondrial disease].

PMID- 11596362
TI  - [Alpers disease(progressive infantile poliodystrophy)].

PMID- 11596363
TI  - [Leigh encephalopathy (subacute necrotizing encephalomyelopathy)].

PMID- 11596364
TI  - [Benign infantile mitochondrial myopathy].

PMID- 11596365
TI  - [Mitochondrial diseases with recurrent myoglobinuria].

PMID- 11596366
TI  - [Pure mitochondrial myopathy].

PMID- 11596367
TI  - [Mitochondrial myopathy/diabetes mellitus].

PMID- 11596368
TI  - [Dementia/ataxia/deafness/myoclonus/retinopathy].

PMID- 11596369
TI  - [May-White syndrome(myoclonus, ataxia, deafness)].

PMID- 11596370
TI  - [Glycogen debranching enzyme deficiency (Forbes-Cori disease)].

PMID- 11596371
TI  - [Optic atrophy/dystonia].

PMID- 11596372
TI  - [Dementia/chorea].

PMID- 11596373
TI  - [Mohr-Tranebjaerg syndrome].

PMID- 11596374
TI  - [Mitochondrial DNA depletion syndrome].

PMID- 11596375
TI  - [Danon disease].

PMID- 11596376
TI  - [Glycogen branching enzyme deficiency (Andersen disease)].

PMID- 11596377
TI  - [X-linked myopathy with excessive autophagy].

PMID- 11596378
TI  - [Rhabdomyolysis].

PMID- 11596379
TI  - [Necrotizing myopathies].

PMID- 11596380
TI  - [Hypokalemic myopathy].

PMID- 11596381
TI  - [Myopathy caused by inhibition of muscle protein synthesis].

PMID- 11596382
TI  - [Phosphoglucomutase deficiency].

PMID- 11596383
TI  - [Antimicrotubular myopathy].

PMID- 11596384
TI  - [Toxin-induced inflammatory myopathy].

PMID- 11596385
TI  - [Corticosteroid myopathy].

PMID- 11596386
TI  - [Amphiphilic cationic drug myopathy, drug-induced lysosomal storage lipidosis].

PMID- 11596387
TI  - [Myopathies in drug addicts].

PMID- 11596388
TI  - [Fasciitis, perimyositis, microangiopathy].

PMID- 11596389
TI  - [Acromegaly].

PMID- 11596390
TI  - [Glycogenosis type VII (glycogen storage disease type VII, human muscle
      phosphofructokinase deficiency, Tarui's disease)].

PMID- 11596391
TI  - [Hypopituitarism].

PMID- 11596392
TI  - [Thyrotoxic myopathy].

PMID- 11596393
TI  - [Myasthenia gravis associated with Graves' disease].

PMID- 11596394
TI  - [Thyrotoxic periodic paralysis].

PMID- 11596395
TI  - [Hypothyroid myopathy].

PMID- 11596396
TI  - [Primary hyperparathyroidism].

PMID- 11596397
TI  - [Secondary hyperparathyroidism].

PMID- 11596398
TI  - [Hypoparathyroidism].

PMID- 11596399
TI  - [Pseudohypoparathyroidism].

PMID- 11596400
TI  - [Cushing syndrome, Cushing disease].

PMID- 11596401
TI  - [Addisonian myopathy].

PMID- 11596402
TI  - [Acquired autoimmune myasthenia gravis].

PMID- 11596404
TI  - [Juvenile myasthenia gravis].

PMID- 11596403
TI  - [Transient neonatal myasthenia gravis].

PMID- 11596405
TI  - [Myasthenia gravis, giant cell polymyositis and cardiomyositis associated with
      thymoma].

PMID- 11596406
TI  - [Autoimmune disorders associated with acquired autoimmune myasthenia gravis].

PMID- 11596408
TI  - [Penicillamine-induced myasthenia gravis].

PMID- 11596409
TI  - [Lambert-Eaton myasthenic syndrome].

PMID- 11596407
TI  - [Aldolase A deficiency].

PMID- 11596410
TI  - [Congenital myasthenic syndrome caused by presynaptic defects].

PMID- 11596411
TI  - [Congenital myasthenic syndrome (CMS) caused by pre- and post synaptic defects].

PMID- 11596412
TI  - [Congenital myasthenic syndrome (CMS) caused by postsynaptic defects].

PMID- 11596413
TI  - [Undetermined congenital myasthenic syndromes].

PMID- 11596414
TI  - [Phosphoglycerate kinase deficiency].

PMID- 11596416
TI  - [Rippling muscle syndrome].

PMID- 11596415
TI  - [Lambert-Brody syndrome].

PMID- 11596417
TI  - [Satoyoshi syndrome (disease)].

PMID- 11596418
TI  - [Acute muscular syndrome in chronic alcoholism--acute necrotizing myopathy, acute
      hypokalemic myopathy].

PMID- 11596419
TI  - [Chronic alcoholic myopathy].

PMID- 11596420
TI  - [Alcoholic cardiomyopathy].

PMID- 11596421
TI  - [Myopathy in malnutrition--malnutrition].

PMID- 11596422
TI  - [Water-soluble vitamin deficiency and muscle-associated syndromes].

PMID- 11596423
TI  - [Fat-soluble vitamin deficiency and muscle-associated syndromes].

PMID- 11596424
TI  - [Diabetic amyotrophy].

PMID- 11596425
TI  - [Muscle phosphoglycerate mutase deficiency].

PMID- 11596426
TI  - [Uremic myopathy].

PMID- 11596427
TI  - [March gangrene].

PMID- 11596428
TI  - [Malignant hyperthermia].

PMID- 11596429
TI  - [Lactic dehydrogenase M subunit (muscle type) deficiency].

PMID- 11596430
TI  - [King syndrome].

PMID- 11596431
TI  - [Atrophy caused by inhibited muscle activity].

PMID- 11596432
TI  - [Meyer-Betz syndrome].

PMID- 11596433
TI  - [Exertional rhabdomyolysis].

PMID- 11596434
TI  - [Ischemic myopathy].

PMID- 11596435
TI  - [Paraneoplastic myopathy and oncogenic osteomalacic myopathy].

PMID- 11596436
TI  - [Botulism].

PMID- 11596437
TI  - [Oculopharyngodistal myopathy].

PMID- 11596438
TI  - [Scapuloperoneal syndrome].

PMID- 11596439
TI  - [Epidemic pleurodynia].

PMID- 11596440
TI  - [Familial carnitine deficiency].

PMID- 11596441
TI  - [Lowe syndrome].

PMID- 11596442
TI  - [Cohen syndrome].

PMID- 11596443
TI  - [Marden-Walker syndrome].

PMID- 11596444
TI  - [Prader-Willi syndrome].

PMID- 11596445
TI  - [Kabuki make-up (Niikawa-Kuroki) syndrome].

PMID- 11596446
TI  - [Intra or intermuscular tumors].

PMID- 11596447
TI  - [Disorders of carbohydrate metabolism (glycogenoses): an overview].

PMID- 11596448
TI  - [Secondary carnitine deficiency].

PMID- 11596449
TI  - [Carnitine palmitoyltransferase deficiency].

PMID- 11596450
TI  - [Carnitine acylcarnitine translocase deficiency].

PMID- 11596451
TI  - [Mitochondrial beta-oxidation defects: overview].

PMID- 11596452
TI  - [Very-long-chain acyl-CoA dehydrogenase deficiency].

PMID- 11596453
TI  - [Medium-chain acyl-CoA dehydrogenase deficiency].

PMID- 11596454
TI  - [Short-chain acyl-CoA dehydrogenase deficiency].

PMID- 11596455
TI  - [Short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) deficiency].

PMID- 11596456
TI  - [Trifunctional protein deficiency and long-chain-3-hydroxy-acyl CoA dehydrogenase
      deficiency].

PMID- 11596457
TI  - [Acid maltase deficiency].

PMID- 11596458
TI  - [Medium-chain 3-ketoacyl-CoA thiolase deficiency].

PMID- 11596459
TI  - [Short-chain 3-ketoacyl-CoA thiolase deficiency (beta-ketothiolase deficiency)].

PMID- 11596460
TI  - [Glutaric aciduria type 2].

PMID- 11596461
TI  - [Myopathies with miscellaneous disorders related to mitochondrial fatty acid
      oxidation: defective synthesis of ketone body, long-chain fatty acid transport
      defect, and muscular coenzyme Q10 deficiency].

PMID- 11596462
TI  - [Disorders of pyruvate metabolism and TCA cycle].

PMID- 11596463
TI  - [Severe subarachnoid hemorrhage--problems and strategy].

PMID- 11596464
TI  - [Problems involved in endovascular embolization of intracranial aneurysms with
      three-dimensional Guglielmi detachable coils].
AB  - We experienced nine cases of intracranial aneurysms which were treated with three
      dimensional Guglielmi detachable coils (3D-GDC). 3D-GDC is useful in the
      construction of the initial frame for the embolization of aneurysms, but it also
      has certain disadvantages for achieving successful treatment. Nine patients with
      nine intracranial aneurysms were treated with 3D-GDC for initial framing from
      October, 1999 to September, 2000 at the National Cardio-Vascular Center, Japan.
      Angiographically complete and successful occlusion was performed in only three
      patients. Four patients developed parent artery stenosis due to small loops of
      the 3D-GDC protruding from the aneurysm. Two patients experienced incomplete
      occlusion because small loops of the 3D-GDC caused cells to form in the framing,
      and additional coils could not be inserted into some cells. 3D-GDC is useful as
      an initial framing coil, but we should be careful when placing additional coils
      into an aneurysm because we cannot predict the effect of the small loops of 3D
      GDC on the embolization of aneurysms.

PMID- 11596465
TI  - [Functional outcome of primary pontine hemorrhage: conservative treatment or
      stereotaxic surgery].
AB  - In this study we compared the outcome of patients with primary pontine hemorrhage
      (PPH) in those who underwent stereotaxic aspiration and those treated non
      surgically. Out of 75 PPHs, 37 patients were selected. Their consciousness on
      admission was somnolent to semicoma (alert and deeply comatose cases were
      excluded). Patients admitted between 1988 and 1990, and between 1995 and 1996
      underwent CT guided stereotaxic aspiration (18 cases: Surgical Group), and those
      admitted between 1991 and 1994 were treated conservatively (19 cases:
      Conservative Group). The outcome was analyzed three months after the onset from
      the viewpoint of level of consciousness and severity of paresis, according to the
      location of the hemorrhage. With regard to consciousness, 13 of 18 cases in the
      Surgical Group showed remarkable improvement, while only 8 of 19 cases in the
      Conservative Group did. The severity of paresis was evaluated only among the
      patients who could obey commands three months after the onset. Paresis improved
      in 7 of 13 patients in the Surgical Group, vs. in 3 of 8 patients in the
      Conservative Group (p < 0.05). According to the location of hemorrhage (CT
      classification), in the Unilateral tegmental type and the Massive type, the
      Surgical Group and the Conservative Group showed no difference. On the other
      hand, in the Bilateral tegmental type and the Basal tegmental type, surgery
      seemed to be more effective than conservative treatment. In conclusion, CT guided
      stereotaxic aspiration may improve not only the consciousness level but also the
      functional outcome.

PMID- 11596466
TI  - [Decompressive craniectomy for massive infarction of middle cerebral artery
      territory].
AB  - There is continuing controversy about the benefits of decompressive craniectomy
      for the treatment of massive infarction of middle cerebral artery (MCA)
      territory. Under conservative therapy, the mortality rate for this stroke is
      reported to be up to 80%. So the authors have actively carried out decompressive
      craniectomy since 1997, and have compared the outcome with patients who were
      admitted before 1997 and, consequently treated with conservative therapy. Fifteen
      consecutive victims of massive infarction of MCA territory were studied. Seven
      patients (male: 1, female: 6, mean age: 79.8 years) were treated with
      conservative therapy, and 8 patients (male: 3, female: 5, mean age: 71.8 years)
      were treated with decompressive craniectomy. There were no significant
      differences in age and consciousness level distribution between the two groups.
      Mortality rate in the conservative therapy group was 85.7% against 12.5% in the
      surgery group (p < 0.05). Functional performance, which was evaluated by activity
      in daily life (ADL), was also better in the surgery group e.g. 3 patients in ADL
      3, and 3 in ADL 4 (1 patient died from a non-neurological cause). Even among the
      patients with speech-dominant hemispheric stroke, all except one were able to
      communicate in some way and understand language. Even though patients in this
      study were elderly, decompressive craniectomy reduced mortality and improved
      functional performance, so it seems that this surgery should be aggressively
      considered for massive infarction of MCA territory.

PMID- 11596467
TI  - [A case of iatrogenic carotid artery dissection treated with radial artery
      graft].
AB  - A case of iatrogenic intracranial artery dissection is reported. A 52-year-old
      female developed severe headache and nausea. Brain CT showed diffuse subarachnoid
      hemorrhage. On admission, carotid angiography revealed an aneurysm in the right
      middle cerebral artery and the intact right internal carotid artery. The aneurysm
      was clipped successfully. Carotid angiography on day 7 revealed dissection in the
      right internal carotid artery. Repeated angiograms at 10 and 31 days showed
      progression of the carotid artery dissection. Findings of ECD-SPECT on day 31
      (Balloon occlusion test) suggested low perfusion of the right internal carotid
      artery territory. The patient underwent surgical reconstruction of the right
      internal carotid artery using a radial artery. She presented with right abducens
      nerve palsy three days after the radial artery graft. The patency of the radial
      artery graft was proved by the post-operative angiography. Internal carotid
      artery dissection may occur spontaneously or as a result of trauma. An iatrogenic
      dissection is an uncommon complication of cerebral angiography. There are no
      evidence-based guidelines for the treatment although anticoagulation therapy is
      most commonly used. The present case emphasizes the usefulness of radial artery
      graft for traumatic carotid artery dissection.

PMID- 11596468
TI  - [Successful treatment of a patient with low pressure syndrome associated with
      gait disturbance].
AB  - The authors report an unusual case of low intracranial pressure (ICP) syndrome
      that was successfully treated by the placement of an anti-siphon device (ASD).
      This 36-year-old male had suffered suprasellar germinoma with hydrocephalus and
      had had a V-P shunt following radiotherapy. Sixteen years later he developed gait
      disturbance and somnolence and MRI demonstrated a small lateral ventricle as well
      as a diffuse dural enhancement. A lumbar tap revealed a low ICP of 12 mmH2O.
      Because of this, an ASD was placed in the patient. Postoperatively, his symptoms
      of gait and consciousness disturbance improved. Typical clinical findings of low
      ICP syndrome such as headache were not observed in this case. To our knowledge,
      no symptom of gait disturbance with low ICP has been reported previously. We
      present an interesting case of low ICP syndrome with gait disturbance and discuss
      the mechanism of the symptoms. Symptoms of this patient were due at first to
      brain ischemia. After convulsion and consciousness disturbance due to low
      intracranial pressure, the symptoms increased in strength until gait disturbance
      occurred. The possibility is suggested that gait disturbance in this patient was
      due both to brain ischemia and low intracranial pressure.

PMID- 11596469
TI  - [A case of spontaneous subarachnoid hematoma of the high cervical spine
      presenting as Brown-Sequard's syndrome].
AB  - Spinal subarachnoid hematoma is a very rare event, occurring exclusively in the
      thoracic or lumbar region. We report the first recorded case of spontaneous
      subarachnoid hematoma in the high cervical spine presenting as Brown-Sequard's
      syndrome. A 57-year-old woman with no prior problems suddenly presented with
      Brown-Sequard's syndrome at the C1-2 disc space level following occiput neck
      pain. Her consciousness was clear and urinary retention was not observed. Lumbar
      puncture revealed no evidence of hemorrhage. Neuroradiological evaluation,
      including myelography, CT myelography, and MRI, demonstrated a defined hematoma
      in the cervical subarachnoid space at the C1-2 level. Angiographical study
      yielded negative findings. The patient's neurological state remained unchanged
      for the following 6 days. On the 7th day from the onset, a C1 and C2 laminectomy
      was performed. A defined clot was found after incising the intact dura matter and
      arachnoid membrane. This clot was easily aspirated except for a small part which
      was found attached to a pial vessel on the dorsal surface of the spinal cord. No
      underlying pathology other than coagulated blood was confirmed. Three months
      postoperatively, she had no neurological deficits. The clinical course of
      spontaneous spinal subarachnoid hematoma varies according to the rapidity and
      severity of hematoma formation. An immediate and precise diagnosis using
      multimodal neuroimagings is vital because decompressive surgery can dramatically
      ameliorate the neurological sequelae.

PMID- 11596470
TI  - [An epithelial cyst at the frontal convexity].
AB  - We report a rare case of an epithelial cyst at the right frontal convexity. A 60
      year-old woman came to our hospital suffering from dysarthria and gait
      disturbance. Computed tomography (CT) of the brain on admission showed a round
      low-density area, 6 cm in diameter, at the right frontal convexity. Midline shift
      and displacement of the lateral ventricle are seen. There is no contrast
      enhancement effect. Excision of the cyst wall and fenestration into the
      subarachnoid space was carried out and the patient was discharged with no
      neurological deficits. After 5 years, regrowth of the cyst was seen. Cyst
      peritoneal shunt was performed and she was discharged uneventfully. Light
      microscopy showed the cyst wall consisted of a monolayer of flat epithelium and
      loose connective tissue. An electronmicrograph of the cyst wall showed a non
      ciliated epithelial layer with microvilli and basement membrane. The epithelial
      cells connecting with each other through desmosome have numerous endoplasmic
      reticulum and mitochondria. Interdigitation of the cytoplasmic membrane was not
      seen. The term "epithelial cyst" seems ambiguous. We discuss the pathogenesis and
      the nomenclature for intracranial benign cystic lesions based on the previous
      literature.

PMID- 11596471
TI  - [Epidural blood patch for the treatment of intracranial hypotension due to
      cerebrospinal fluid leakage after thoracic spine surgery].
AB  - We report a case of a 44-year-old woman successfully treated by an epidural blood
      patch for intracranial hypotension due to cerebrospinal fluid (CSF) leakage into
      the thoracic cavity after thoracic spine surgery. The patient was admitted to our
      hospital with the complaint of postural headaches. She had received anterior
      thoracic instrumentation for thoracic disc herniation four months earlier. Lumbar
      puncture demonstrated low CSF pressure, and Gd-enhanced MR images displayed
      diffuse dural enhancement. Accordingly, she was diagnosed as having intracranial
      hypotension. 111In-DTPA cisternography revealed a CSF leakage into the left
      thoracic cavity, possibly caused by dural laceration during thoracic spine
      surgery. To avoid the risk of direct surgery, we performed epidural blood patch;
      3 ml of autologous blood was injected into the epidural cavity. Postoperatively
      postural headaches immediately disappeared. MRI taken one year later revealed
      disappearance of diffuse dural enhancement, and 111In-DTPA cisternography
      revealed no CSF fluid leaks. Epidural blood patch seems to be a choice of
      treatment for CSF leak after spinal surgery.

PMID- 11596472
TI  - [Two cases of "steal VBI" with stenosis of the internal carotid artery].
AB  - Although previous reports have suggested "steal VBI" due to occlusive carotid
      artery diseases, there have been no reports that clearly define "steal VBI" from
      the viewpoint of cerebral hemodynamics. The authors presented two cases with
      "steal VBI" due to severe stenosis of the internal carotid artery. Both patients
      had well-developed collateral circulation through the ipsilateral posterior
      communicating artery. Although no occlusive lesion was found in the
      vertebrobasilar system, blood flow studies revealed impaired hemodynamics in the
      contralateral occipital lobe, which fact correlated with their neurological
      deficit, visual field disturbance. Carotid stenting markedly corrected the
      stenotic lesions, leading to neurological improvement. Follow-up blood studies
      showed normalization of hemodynamics in the contralateral occipital lobe. The
      findings strongly suggest that carotid surgery or stenting can improve cerebral
      hemodynamics in the carotid systems, resolving "steal VBI" due to developed
      collaterals from the posterior to the anterior circulation.

PMID- 11596473
TI  - [A case of thoracic vertebral tuberculosis associated with pulmonary
      sarcoidosis].
AB  - A 56-year-old woman was admitted to our hospital, on October 10, 1999 because of
      tingling numbness of the Th3 area and paraparesis. Her medical history included
      the diagnosis of pulmonary sarcoidosis which had responded to steroid therapy. On
      radiographic examination, a Th2 compression fracture and gadolinium enhanced
      areas were shown in MRI. We diagnosed vertebral sarcoidosis and restarted steroid
      therapy. Next day, she had no paresis and she was discharged after 20 days.
      However, the patient returned to our hospital with recurrence of the same pain
      and paraparesis on January 1, 2000, and spinal fusion of the Th2-3 was performed
      by a transpleural anterolateral approach using a block of iliac bone as a graft.
      Histology and cultural studies of tissue revealed tuberculosis. There is a
      diagnostic dilemma, "sarcoidosis or tuberculosis?", but it is necessary to be
      aware of this at the time of the initial diagnosis.

PMID- 11596474
TI  - [ALS models by transgenic animals].

PMID- 11596475
TI  - [Development of transgenic animal models for Alzheimer's disease].

PMID- 11596476
TI  - [Recent advances in the prion animal models].

PMID- 11596477
TI  - [Huntington's disease model mouse and neuronal cell death].

PMID- 11596478
TI  - [Understanding of polyglutamine diseases through transgenic mouse models].

PMID- 11596479
TI  - [Ictal semiology in patients with medial temporal lobe epilepsy: value in
      lateralizing the seizure focus].
AB  - We have evaluated useful lateralizing signs in 28 patients with medial temporal
      lobe epilepsy who were seizure-free after anterior temporal lobectomy by
      reviewing videotapes during video-EEG monitoring. The most frequent types of aura
      were epigastric sensation and psychic symptom in 8, respectively, both of which
      did not predict lateralization of the focus. Of the motor signs, early head
      deviation and unilateral upper extremity automatism predicted an ipsilateral
      focus in 72 and 80%, respectively. On the other hand, late head deviation(< 15
      seconds before secondarily generalized seizure) and unilateral upper extremity
      dystonic posturing predicted a contralateral focus in 80 and 100%, respectively.
      Twelve of the patients displayed oroalimentary automatism which did not predict
      focus lateralization. Three patients with ictal speech demonstrated a seizure
      focus contralateral to their language-dominant hemisphere. In medial temporal
      lobe epilepsy, several clinical seizure manifestations such as: early and late
      head deviation, unilateral upper extremity automatism and dystonic posturing were
      not a little noted and provided additional information as to the side of seizure
      origin.

PMID- 11596480
TI  - [Experimental study of pharmacological hypothermia: enhanced neuroprotective
      effect of a novel 5-HT 1 A agonist SUN N4057 by the pharmacological hypothermia].
AB  - PURPOSE: 5-hydroxytryptamine(5-HT) 1 A receptor agonists have a potentially
      marked neuroprotective reaction by both neuroprotective and hypothermic effects.
      We previously reported (1) the neuroprotective effect against the cerebral
      ischemia under normothermic condition, and (2) the hypothermic effect of the
      novel compound of 5-HT 1 A agonist, SUN N4057. The present investigation was
      designed to examine the enhancement of the neuroprotective effect by its
      pharmacological hypothermia. METHODS: In 24 anesthetized cats(body weight 1.9-4.6
      kg), the left middle cerebral artery(MCA) occlusion was performed via the
      transorbital approach. Just after MCA occlusion, SUN N4057(6 micrograms/kg/min)
      was infused. Physiological parameters were measured continuously, and arterial
      blood gas was analyzed hourly for 6 hours and maintained within the normal
      ranges. Animals were randomly allocated to the following three groups: (1)
      ischemic controls infused with sterile saline(Group A, n = 8), (2) SUN N4057
      under normothermic condition(Group B, n = 8), (3) SUN N4057 (Group C, n = 8).
      Then, brain coronal sections of 3 mm in thickness were stained with 1%
      triphenyltetrazolium chloride(TTC) solution, and hemispheric infarct volumes were
      calculated by using a computerized image analysis system. RESULTS: There were no
      significant differences in any physiological parameters among 3 groups. In Group
      C, brain temperature decreased significantly starting 1 hour after MCA occlusion
      and dropped by 2.1 +/- 0.7 degrees C 5 hours. Infarct volumes were 35.6 +/- 6.9%
      (Group A), 23.3 +/- 5.8% (Group B) and 12.3 +/- 11.3% (Group C), respectively.
      There were significant differences among three groups(p < 0.05). CONCLUSION: On
      the basis of these data, we conclude that SUN N4057 provides more effective
      neuroprotection by the combination of hypothermic and neuroprotective effects.
      Chemical hypothermia may lead to a new therapeutic approaches for treatment of
      brain ischemia.

PMID- 11596481
TI  - [Transverse myelopathy with renovascular hypertension caused by fibromuscular
      dysplasia].
AB  - An 18-year-old woman developed subacute transverse myelopathy with renovascular
      hypertension, hyperlipidemia, and proteinuria. Spinal magnetic resonance
      imaging(MRI) showed an intra-spinal cord lesion with severe spinal cord swelling
      at the C 2-Th 2 level. Increased plasma and cerebrospinal fluid interleukin-8(IL
      8) levels and the presence of serum antineutrophil cytoplasmic antibody(ANCA)
      suggested the existence of an ischemic lesion due to vasculitis. Administration
      of corticosteroids ameliorated the clinical symptoms and MRI findings.
      Renovascular angiogram revealed the presence of fibromuscular dysplasia(FMD) at
      the left renal artery but no malformation was found at the cervical arteries. We
      discussed the possibility of relationships between myelopathy, FMD, IL-8, and
      ANCA.

PMID- 11596482
TI  - [A case of cholinergic urticaria with epileptic seizure and abnormalities on
      electroencephalogram].
AB  - We report a 10-year-old boy with cholinergic urticaria associated with epileptic
      seizure and abnormalities on electroencephalogram. In March 1999, many red wheals
      developed over the entire body during exercise and at increased body temperature.
      In April, systemic red wheals developed during exercise. Simultaneously, loss of
      consciousness was noted for 2 to 3 minutes. After the patient's body was cooled,
      consciousness improved, and these exanthemas disappeared. In the Department of
      Dermatology, his illness was diagnosed as cholinergic urticaria. Neurologically,
      a heat tolerance and mental strain induced cholinergic urticaria, followed by
      generalized epilepsy(clonic seizure). In addition, electroencephalography
      revealed high voltage polyspikes and 14 Hz positive spikes. The mechanism
      involved in cholinergic urticaria associated with epileptic seizure was assumed
      as follows: sweat-promoting stimuli, such as heat, exercise and tension,
      stimulate the autonomic center in the diencephalon or brain stem, and excitation
      in the autonomic center is transmitted to the efferent sympathetic nerve, causing
      cholinergic urticaria; when the intensity of stimulation is high, the autonomic
      center exhibits abnormal activities and causes epileptic seizure.

PMID- 11596483
TI  - [Hand motor cortical area reorganization following cerebral infarction evaluated
      with functional MRI, near infrared spectroscopic imaging, and transcranial
      magnetic stimulation].
AB  - A 60-year-old, right-handed man suffered from left hemiparesis with upper limb
      dominance. CT and MRI revealed cerebral infarction of the entire right middle
      cerebral artery territory. His hemiparesis recovered excellently and residual
      neurological deficits 6 years later were left hand weakness(grasping power 9 kg
      vs. 35 kg in the right) and clumsiness. Functional MRI was performed. During
      right(normal) hand grasping, activation was seen in the left sensorimotor cortex
      and supplementary motor area. During left(paretic) hand grasping, activation was
      seen in the left (ipsilateral) sensorimotor cortex, right parietal cortex, and
      bilateral supplementary motor areas. Near infrared spectroscopic imaging showed
      similar results. During right hand grasping, left sensorimotor cortex was
      activated, and during left hand grasping, bilateral sensorimotor cortices were
      activated with ipsilateral predominance. Transcranial magnetic stimulation of the
      left motor hand area evoked right hand movement and stimulation of a point near
      that area evoked ipsilateral left hand muscle movement. Thus, the findings of the
      three techniques consistently suggest that the recovery of left hemiparesis of
      this patient was promoted by motor cortical area reorganization including the
      ipsilateral motor cortex.

PMID- 11596484
TI  - [Neuropathology of longstanding subacute myelo-optico-neuropathy (SMON): an
      autopsy case of SMON with duration of 28 years].
AB  - The present case, 78-years-old female, had been troubled with SMON during 28
      years, and was suddenly died from cerebral hemorrhage. The neuropathology
      characteristic for SMON could not be revealed in the spinal cord on routine
      histological preparations. There were decreasing number of immunopositive
      granules in the nucleus gracilis of medulla oblongata for synaptophysin, and in
      the marginal zone of the lumbar dorsal horn for substance P. These findings
      showed the presence of tractus gracilis degeneration and the disappearance of
      nociceptive fibers from the dorsal roots, respectively. To elucidate the
      histopathological changes of the spinal cord in long standing cases with SMON,
      the 11 cases reported were reviewed. The mean duration from the onset to death
      was 22.8 years(16 to 33 years). The mean age was 76.3 years old(54 to 92), and
      the 10 cases were female. All cases showed sensory impairment of the lower
      extremities, while deep tendon reflex exaggerated was seen in 7 cases. There were
      nine cases involving dorsal funiculi degeneration of the spinal cord, in contrast
      the lateral funiculi alternation were noticed in only two cases. It was
      considered that the corticospinal tract alteration becomes undiscernible during
      the long course, although the dorsal funiculi degeneration remained.

PMID- 11596485
TI  - [Cerebral arteritis and cerebritis caused by subdural empyema: two cases report].
AB  - We report two cases of cerebral angitis and cerebritis caused by subdural
      empyema. A 22-year-old man, who complained of a headache and high fever, suddenly
      developed unconsciousness and right hemiparesis. CT and MRI demonstrated left
      subdural empyema with diffuse brain swelling. CT angiography showed diffuse
      narrowing of the left internal carotid artery, middle cerebral artery, and
      anterior cerebral artery. Although we performed craniotomy, continuous irrigation
      with drainage, systemic injection of antibiotics for subdural empyema,
      antiplatelet therapy, and hyperbaric oxygen therapy for angitis, his condition
      remained unchanged. A 67-year-old man who had previously undergone burr hole
      surgery presented to our hospital for the treatment of scalp infection. He
      suddenly developed unconsciousness and right hemiparesis. CT and MRI demonstrated
      left subdural empyema with diffuse brain swelling, but MR angiography did not
      show any abnormal findings. Hemiparesis improved after the surgery and systemic
      injection of the antibiotics. Subdural empyema with sinusitis or meningitis
      around the skull base sometimes causes cerebral angitis. We considered that the
      angiographical evaluation for the subdural empyema was necessary to detect
      angitis.

PMID- 11596486
TI  - [A case of cerebellar tonsil infarction diagnosed with MR imaging].

PMID- 11596487
TI  - [A case of cerebral infarction of parietal cortex with palmar sensory disturbance
      resembling as carpal tunnel syndrome].

PMID- 11596488
TI  - Characterisation of microtubule-associated proteins at the synapse: absence of
      MAP 2.
AB  - The high molecular weight microtubule-associated proteins MAP 1 and MAP 2 are
      major components of brain cytosol and can be readily identified using
      polyacrylamide gel electrophoresis on the basis of heat-stability and co
      sedimentation with microtubules. An examination of synaptosomal cytosol, synaptic
      plasma membrane and postsynaptic density fractions showed that MAP 2 is absent
      from these fractions and thus from both pre- and postsynaptic sites. All of the
      fractions contained polypeptides that comigrated with MAP 1 and a MAP 1 like
      polypeptide was identified in a microtubule preparation from synaptosomal
      cytosol. The absence of MAP 2 from synaptosomal cytosol was confirmed by
      immunoblotting using an antibody directed against MAP 2. Immunocytochemistry
      using this antibody showed that MAP 2 was present in cell bodies and dendrites
      but absent from axons.

PMID- 11596489
TI  - The induction of de novo centrioles in sea urchin eggs: a possible common
      mechanism for centriolar activation among parthenogenetic procedures.
AB  - Eggs from two species of sea urchins were subjected to a variety of novel two
      step parthenogenetic activation procedures. These treatments readily resulted in
      the formation of cytasters and centrioles. Centrioles are restricted to the
      cytasters, as well as to the broad perinuclear zone, and it appears that all
      cytasters contain one or more centrioles. The mode of centriolar origin and
      maturation, as revealed by these new procedures, is identical to that of
      centrioles induced by other procedures. Both centriolar and cytastral development
      are retarded by the parthenogenetic treatments; also, mitosis is generally
      delayed. These results, along with those of others, reveal that parthenogenetic
      agents have opposing effects on eggs. The agents are stimulatory in that they
      activate latent centrioles and the cell cycle, in general. They are inhibitory in
      that they suppress a variety of physiochemical events. Of these events, only one
      appears to be common to all parthenogenetic agents: the inhibition of protein
      synthesis. Egg centrioles may be kept in a latent state by repressor proteins. If
      these proteins normally cycle rapidly, then an inhibition of their continuous
      synthesis will disrupt their normal replacement rate. As such, a delay in
      replacement will allow functioning repressor proteins, associated with latent
      centrioles, to become nonfunctional, which in turn allows latent centrioles to
      become derepressed. This deblocking reaction would then activate the appearance
      of de novo centrioles in eggs.

PMID- 11596490
TI  - Distribution of actin and the actin-associated proteins myosin, tropomyosin,
      alpha-actinin, vinculin, and villin in rat and bovine exocrine glands.
AB  - Actin, myosin, and the actin-associated proteins tropomyosin, alpha-actinin,
      vinculin, and villin were localized in acinar cells of rat and bovine pancreas,
      parotid, and prostate glands by means of immunofluorescent staining of both
      frozen tissue sections and semithin sections of quick-frozen, freeze-dried, and
      plastic-embedded tissues. Antibodies to actin, myosin, tropomyosin, alpha
      actinin, and villin reacted strongly with a narrow cytoplasmic band extending
      beneath the luminal border of acinar cells. The presence of villin, which has so
      far been demonstrated only in intestinal and kidney brush border, was further
      confirmed by antibody staining of blotted electrophoresis gels of whole acinar
      cell extracts. Fluorescently labelled phalloidin, which reacts specifically with
      F-actin, gave similar staining, within the cell apex to that obtained with
      antibodies to actin, myosin, tropomyosin, alpha-actinin, and villin. In contrast,
      immunostaining with antibodies to vinculin was restricted to the area of the
      junctional complex. Ultrastructurally, the apical immunoreactive band
      corresponded to a dense web composed of interwoven microfilaments, which could be
      decorated with heavy meromyosin. Outside this apical terminal web, antibodies to
      myosin and tropomyosin gave only a weak immunostaining (confined to the lateral
      cell borders) whereas antibodies to actin and alpha-actinin led to a rather
      strong bead-like staining along the lateral and basal cell membrane most probably
      marking microfilament-associated desmosomes. Anti-villin immunofluorescence was
      confined to the apical terminal web. It is suggested that the apical terminal web
      is important for the control of transport and access of secretory granules to the
      luminal plasma membrane and that villin, which is known to bundle or sever actin
      filaments in a Ca(++)-dependent manner, might participate in the regulation of
      actin polymerization within this strategically located network of contractile
      proteins.

PMID- 11596491
TI  - Visualization of freeze-dried and shadowed myosin molecules immobilized on
      electron microscopic films.
AB  - The mica replication technique first described by Hall [5] has produced myosin
      molecules which were heterogeneous in appearance in terms of shadowing,
      decoration, contrast and background. Therefore, an alternative technique for the
      visualization of myosin molecules was developed: Myosin molecules are sprayed
      directly onto glow discharged or silicium-monoxide coated carbon filmed grids,
      omitting glycerol. After washing several times with distilled water, rapid
      freezing, and freeze-drying, the immobilized myosin molecules are visualized by
      shadow-casting at low temperature and at varying angles. After backing with
      carbon the "in situ" shadowed molecules are observed in the electron microscope.
      This technique has several advantages over the standard method in that it yields
      more reproducible results. It is potentially useful for investigating
      interactions of myosin binding proteins with myosin and for visualizing
      unshadowed myosin in the STEM.

PMID- 11596492
TI  - Microfilaments and intermediate filaments in epithelial cells transformed by
      murine sarcoma or leukemia viruses.
AB  - The murine epithelial cell line MMC-E was used to study changes in the
      cytoskeletal organization associated with viral transformation of epithelial
      cells by two different viruses. The cells were transformed with Moloney mouse
      sarcoma virus (MSV) or murine leukemia virus (MuLV). The expression of actin,
      myosin and of intermediate filament proteins in the cells was then studied. In
      MMC-E cells actin and myosin were organized as belt-like structures at the edges
      of the border cells of the cell islands and also circumferentially in the cells
      inside the islands. The major change after transformation was the decrease of the
      actomyosin containing belt extending from cell to cell at the borders of the cell
      islands. Both MMC-E cells and the MSV-transformed cells contained keratin as a
      juxtanuclear granular aggregate whereas the MuLV-transformed cells showed bright
      fibrillar arrays of keratin. Both virus-transformed cell lines showed enhanced
      vimentin-specific fluorescence and analysis of their cytoskeletal polypeptides
      confirmed the result. Similar molecular forms of keratin polypeptides were seen
      in all cells by immunoblotting. Viral transformation of MMC-E epithelial cells
      thus leads to different changes in their cytoskeletal organization depending on
      the transforming viral or cellular gene.

PMID- 11596493
TI  - Intracellular and extracellular localization of fibronectin in primary cultures
      of aortic smooth muscle cells using immunoperoxidase cytochemistry in electron
      microscopy.
AB  - This report describes the intracellular and extracellular localization of
      fibronectin at the ultrastructural level in primary cultures of aortic smooth
      muscle cells. Fibronectin was present in all the cisternae of the rough
      endoplasmic reticulum except the perinuclear cisterna, in large vesicles
      associated with the trans side of the Golgi complex, and in single large vesicles
      in the cytoplasm often associated with microtubules. The extracellular
      microfibrils were heavily stained. In sections parallel to the plane of growth
      bundles of extracellular microfibrils in continuity with arrays of intracellular
      microfilaments were observed (fibronexus). The basement membrane around the
      aortic smooth muscle cells was discontinuous and diffusely stained. The results
      indicate that fibronectin is localized in the cytoplasmic membranous apparatus of
      protein synthesis, processing, and secretion. The lack of reaction product in the
      flat cisternae of the Golgi complex let suggest either that fibronection may not
      be present in significant amounts within the flattened cisternae or that the
      method is insufficient in detecting the glycoprotein in this subcompartment off
      the Golgi complex.

PMID- 11596494
TI  - Fibronectin in cultured rat keratinocytes: distribution, synthesis, and
      relationship to cytoskeletal proteins.
AB  - The aim of this study was to investigate whether epidermal cells can synthesise
      fibronectin and whether the distribution of this glycoprotein is related to the
      adhesion and cytoskeletal organisation of these cells. The production of
      fibronectin by newborn rat epidermal cells was shown by indirect
      immunofluorescence staining of cultures grown in the absence of a feeder layer
      using an antiserum which had been cross-adsorbed with foetal calf serum proteins
      to remove antibodies which recognised serum fibronectin. The distribution of
      fibronectin in areas of cell-cell and cell-substratum contact, characteristically
      in the form of short radial stitches, was examined in more detail using
      immunoelectron microscopy with colloidal gold as marker. This showed the close
      proximity of fibronectin to the cell membrane, with the ventral surface and fine
      cellular processes showing the heaviest labelling, and also revealed evidence of
      a relationship between external fibronectin and internal structure in epidermal
      cells. Immunofluorescence showed that tonofilaments (keratin) and microtubules
      were present as fibrillar arrays but were not related to fibronectin
      distribution. Vimentin and desmin were absent. Actin was distributed as a
      circumferential bundle of filaments, with finer stands running radially to the
      edge. The latter were reminiscent of the radial fibronectin stitches and a
      spatial correspondence between fibronectin and actin was confirmed by double
      label immunofluorescence which revealed many instances of overlap and colinearity
      of actin and fibronectin filaments. The ability of keratinocytes to produce
      fibronectin suggests that these cells can contribute to the formation of the
      basement membrane in skin. The localisation of fibronectin and its close
      association with actin also suggests that it is involved in keratinocyte adhesion
      and is related to the internal organisation of these cells.

PMID- 11596495
TI  - Calelectrin in human blood cells.
AB  - Calelectrin is a new calcium-binding protein isolated from the cholinergic nerve
      terminals of the electric organ of Torpedo marmorata, which is widely distributed
      in nervous tissues and selectively binds to membranes, self-aggregates, and
      promotes calcium-induced membrane aggregation as a function of calcium
      concentration. We now show by immunofluorescence and immune blotting procedures
      that this protein is also present in human blood cells. Immunofluorescence
      demonstrates calelectrin in all human leucocytes, including mononuclear cells,
      but not in platelets or in erythrocytes. The immunofluorescence indicates an
      exclusively cytoplasmic location of calelectrin with a diffuse distribution and
      no primary association with the cytoskeleton or the cell membranes. SDS
      polyacrylamide gel electrophoresis with immune blotting of fractionated blood
      cells (thrombocytes, mononuclear cells, granulocytes and erythrocytes) reveals
      the presence of a single protein crossreactive with calelectrin from Torpedo
      marmorata in the granulocyte and mononuclear cell fractions only. Human
      calelectrin has a molecular weight similar to Torpedo calelectrin (approximately
      34-35 kD) and also binds to membranes in a Ca(2+)-dependent manner. Our results
      have several implications: (1) Calelectrin is conserved during evolution between
      the fish Torpedo marmorata and humans; (2) its expression in neural and
      mesenchymal cells points to an important functional role of the protein; (3) its
      absence from platelets excludes the hypothesis that it is a necessary participant
      in exocytosis per se and suggests some other function in Ca(2+)-triggered
      processes.

PMID- 11596496
TI  - The structure and development of the rat retina: an immunofluorescence
      microscopical study using antibodies specific for intermediate filament proteins.
AB  - Rat retina structure was studied between embryonic day 14 and adult with
      antibodies specific for vimentin, glial fibrillary acidic protein (GFA) and the
      proteins of the neurofilament triplet. Vimentin could be detected in radial
      processes throughout the retina at all stages studied. These processes are
      believed to correspond, in the developing retina, to ventriculocytes, and in the
      mature retina to Muller cells. They could not normally be stained with any of the
      other intermediate filament antibodies employed here. We did find, however, that
      some older albino rats possessed GFA staining in addition to vimentin in these
      processes. Since we never saw such staining in the retinae of mature non-albino
      rats, and the retinae of older albino rats often showed signs of degeneration, we
      concluded that such GFA expression was most likely pathological. Neurofilament
      protein-positive processes were first detectable at embryonic day 15 1/2 in the
      inner regions of the retina, and corresponded to the axons of retinal ganglion
      cells. Such processes were equivalently displayed with antibodies to 68 K and 145
      K protein, but were negative with 200 K protein. Some 68 K and 145 K positive
      fibers could also be decorated with vimentin antibody at this stage, though at
      later stages this was not the case. At later development stages more 68 K and 145
      K neurofilament positive processes appeared, and after the first post-natal week
      progressively more of such processes became in addition 200 K positive, so that
      almost all neurofilament positive fibers in the adult stained for all three
      proteins. Such fibers, in the mature retina corresponded to 68 K and 145 K
      positive optic nerve fibers, and the processes of neurones in the inner plexiform
      layer. All fibers in the mature optic nerve fiber layer, but not all of those in
      the inner plexiform layer were stainable with 200 K antibodies. At 4 days post
      natal we were able to detect 68 K and 145 K protein positive profiles in the
      outer regions of the developing retina, the prospective outer plexiform layer.
      Such profiles were always in addition vimentin positive, but negative for 200 K
      protein. During further development such profiles became ordered into a well
      defined layer and from about post-natal day 13 all of them began to acquire 200 K
      protein. They could be identified as the processes of horizontal cells. They
      continued to express vimentin in addition to the three triplet proteins in the
      adult, a so far unprecedented situation. We were able to detect neurofilament
      staining in the mature retina only in the above described regions, the inner and
      outer nuclear layer and the photoreceptor processes being completely free of
      staining. GFA was first detected in short processes adjacent to the inner
      limiting membrane which penetrated the optic nerve fiber layer. Such profiles
      were first detectable in the eye of the newborn animal, and were invariably
      identically stainable with vimentin at this age. These profiles could be stained
      with both vimentin and GFA at all later stages examined, although GFA staining
      became very much stronger than vimentin staining in some profiles in the adult.
      The results presented here are discussed in terms of development of the different
      retinal cell types.

PMID- 11596497
TI  - Membrane shuttle between plasma membrane, phagosomes, and pinosomes in
      Dictyostelium discoideum amoeboid cells.
AB  - The intracellular redistribution of membrane internalized during endocytosis was
      studied quantitatively by a biochemical approach and by a morphometric analysis
      of autoradiographs in electron microscopy. Plasma membrane glycoconjugates,
      enzymatically labelled with radioactive galactose, were used as a membrane
      marker. In cells labelled at their surface either before or after the
      phagocytotic uptake of latex beads, subsequent endocytosis led to a
      redistribution of label between the plasma membrane and endosomal membranes until
      a steady-state was reached after about 1 h with 43% of the label on the plasma
      membrane. The steady-state resulted when all participating membranes carried the
      same surface density of label. During phagocytosis or pinocytosis the equivalent
      of the plasma membrane was internalized and recycled once every 20 min or 40 min,
      respectively. Compared to this rate a very rapid and complete mixing of membranes
      was observed between newly formed phagosomes and preexisting digestive vacuoles
      or between newly formed pinosomes and preexisting phagosomes. Due to this rapid
      mixing, the membranes enclosing undigestible latex beads remained fully linked to
      the shuttle of membrane to and from the cell surface.

PMID- 11596498
TI  - [Prolactin internalisation by the epithelial mammary cell: effects of
      lysosomotropic agents and transglutaminase inhibitors].
AB  - Prolactin endocytosis was studied by electron microscopy with 125I-prolactin 125I
      hGH (human growth hormone) and prolactin-ferritin. Endocytosis and intracellular
      transit of the labelled hormone proceeded identically in epithelial cells
      isolated from the mammary glands of pseudopregnant rabbits and in surviving
      fragments from mammary glands of lactating rabbits. After binding of the hormone
      to its receptor, the labelled material was rapidly detectable in vesicles showing
      an homogeneous aspect; 15 min later part of the labelled material was still
      localized within the same kind of vesicles, but in addition it appeared to have
      migrated into microvesicles of the Golgi region and into vesicles of
      heterogeneous aspect tentatively identified with lysosomes. Endocytosis of bovine
      serum albumin, labelled with ferritin followed the same intracellular pathway.
      Native ferritin accumulated in vesicles of various sizes, but seemed excluded
      from the microvesicles of the Golgi zone. In the presence of lysosomotropic
      agents labelled prolactin accumulated in cytoplasmic vesicles. In the presence of
      dansylcadaverine, endocytosis of the labelled material proceeded unimpaired.
      Conversely, in the presence of bacitracin, the internalisation of labelled
      prolactin seemed to be reduced. These observations show that the endocytosis of
      the hormone/receptor complex is linked to membrane movements, which eventually
      lead to its location within both the Golgi apparatus and the lysosomes.

PMID- 11596499
TI  - Acid phosphatase associated with discharging secretory vesicles (mucocysts) of
      Tetrahymena thermophila.
AB  - The localization of acid phosphatase in discharging mucocysts of Tetrahymena
      thermophila is reported. Electron dense, lead phosphate enzyme reaction product
      is found associated with the fibrillar meshwork of secreting mucocysts and in
      cytoplasmic vesicles (e.g. lysosomes). Resting mucocysts, containing highly
      condensed contents, exhibit no label. The specificity of the stain was controlled
      by reaction media without exogenous substrate and reaction media containing the
      inhibitor sodium fluoride. No lead phosphate deposits were found in these
      controls. Secreting organelle contents have no preferential affinity to lead
      phosphate as shown by tests with reaction medium lacking substrate and subsequent
      incubation in phosphate containing medium.

PMID- 11596500
TI  - A freeze-fracture study on the differentiation of Golgi and plasma membranes in
      plant cells.
AB  - Dictyosomes, Golgi vesicles, and plasma membranes were investigated after freeze
      fracture in cells from growing root tips of cress (Lepidium sativum L.), that are
      distinguishable by different cellulose content of the cell wall, into (i)
      meristematic cells during early formation of the cell plate, (ii) statocytes of
      the root cap, and (iii) cortex cells of the differentiation zone. The results of
      this study show that the number of intramembrane particles (imps) is high in
      dictyosome cisternae, but low in membranes of budding or dictyosome-derived
      vesicles. Imps are disperse in the vesicle membranes of meristematic cells (i),
      but are often grouped into clusters in vesicle membranes of statocytes (ii), and
      of cortex cells (iii). For the number of particle aggregates in vesicle
      membranes, the following relation holds: (i) < (ii) < (iii). The number of
      particles on both fracture faces (PF and EF) of the plasma membrane differs
      widely between the cell types investigated. There are approximately 250, 1400,
      and 3100 imps microns-2 on the PF and 50, 500, and 300 on the EF of (i), (ii),
      and (iii), respectively. The structural complexity of the plasma membrane as
      judged by the degree of particle aggregations on the PF and the number of
      cellulose microfibrils in the cell wall show the same relationship: (i) < (ii) <
      (iii). Thus, the strong correlation between the distribution of imps in vesicle
      membranes, the structural complexity of the plasma membrane, and the content of
      cellulose microfibrils indicate that selection of imps during vesicle formation
      at dictyosome cisternae is an integral component of biogenesis and structural
      differentiation of plant plasma membranes.

PMID- 11596501
TI  - Sinusoidal endothelial endocytosis of low density lipoprotein-gold conjugates in
      perfused livers of ethinyl-estradiol treated rats.
AB  - We examined endocytosis of low-density lipoproteins (LDL) conjugated to colloidal
      gold by the sinusoidal endothelium in perfused livers of 17 alpha-ethinyl
      estradiol-treated rats. After 15 min of perfusion, the gold-LDL was randomly
      bound at the endothelial surface, but internalized only at coated pits. Uptake of
      the conjugate was to electron-lucid vacuoles. After 1 h of perfusion, there was a
      progressive accumulation of gold in organelles resembling lysosomes, with further
      accumulation seen at 2 h perfusion. Uptake of the conjugate was equivalent to the
      rate of 125I-LDL and competitively inhibited by a 20-fold excess of free LDL.
      These results suggest that a specific endocytotic pathway for LDL is present in
      the sinusoidal endothelium in the estrogen-hypolipidemic state.

PMID- 11596502
TI  - Thyroid lysosomes: the stability of the lysosomal membrane.
AB  - To determine the integrity of lysosomes during their isolation from rat thyroid
      glands and their subsequent incubation at 37 degrees C, the sedimentability of
      lysosomal acid phosphatase and thyroglobulin (amount of undisrupted lysosomes)
      and the latency of sedimentable acid phosphatase (permeability of undisrupted
      lysosomes) were measured concomitantly. The following results were obtained: (a)
      During isolation of lysosomes in 0.25 M sucrose medium, mild homogenization of
      thyroid tissue or cholesterol addition did not modify the amount of undisrupted
      lysosomes but reduced their permeability. Homogenization in 0.5 M sucrose
      decreased both the amount and the permeability of undisrupted lysosomes. It also
      reduced their content of recently iodinated thyroglobulin (Tg). Cholesterol
      addition had no effect in 0.5 M sucrose medium. (b) During incubations at 37
      degrees C of lysosomes, the amount of undisrupted lysosomes decreased
      progressively while their permeability increased. According to the incubation pH,
      the permeability of lysosomes prepared in 0.25 M sucrose was either more (pH 8)
      or less (pH 6) extensively increased than that of lysosomes prepared in 0.5 M
      sucrose. From these results, we concluded: (a) that isolation and incubation of
      the thyroid lysosomal fraction induce increased permeability of lysosomes prior
      to their complete disruption: (b) that recently formed lysosomes (high content of
      recently iodinated Tg) and aged lysosomes (low content of recently iodinated Tg)
      differ significantly. Recently formed lysosomes are more permeable, are
      stabilized by cholesterol and are more extensively disrupted in 0.5 M sucrose
      medium. During incubations, the permeabilities of these two classes of lysosomes
      are also differently affected by external pH.

PMID- 11596503
TI  - Plastid envelopes in reproductive cells.
AB  - During oogenesis in the fern Paesia the plastid envelopes become progressively
      less distinct following aldehyde fixation and osmication, but react normally to
      permanganate. Consideration of the formation of the membrane image by osmium and
      by permanganate leads to the conclusion that the lipids of the envelope membranes
      become less unsaturated as the egg matures. This may increase permeability of the
      envelope and facilitate metabolic interchange with the ground cytoplasm. The
      mitochondrial envelopes remain unchanged throughout oogenesis. Similar behaviour
      of the plastid envelope has been observed during the differentiation of other
      reproductive cells, both spores and gametes.

PMID- 11596504
TI  - Studies on the contractile vacuole of Poterioochromonas malhamensis Peterfi. II.
      Antimonate stains the contractile vacuole of Poterioochromonas.
AB  - Fixation of the chrysophycean flagellate Poterioochromonas malhamensis in the
      presence of potassium (pyro) antimonate have been carried out. Intense antimonate
      deposits are characteristic of the various elements of the contractile vacuole as
      well as a portion of the plasma membrane adjacent to the contractile vacuole.
      Neither pretreatment of the cells with EGTA or EDTA nor the treatment of sections
      with these chelators is successful in removing the antimonate precipitates.
      Despite this, X-ray microanalyses of these deposits indicate the presence of
      calcium.

PMID- 11596505
TI  - Nuclear ornithine decarboxylase. Electron microscope autoradiographic
      identification of the active enzyme using alpha-[5-3H]difluoromethylornithine.
AB  - alpha-Difluoromethylornithine (DFMO) is an enzyme-activated irreversible
      inhibitor of ornithine decarboxylase, that forms a covalent bond with the active
      enzyme. The highly selective binding of tritium-labeled DFMO to ornithine
      decarboxylase in vivo, as identified by electron microscope autoradiography, was
      used to determine the intracellular distribution of the enzyme in the germ cells
      of a polychaete (Ophryotrocha labronica). In mid-oogenesis ornithine
      decarboxylase was predominantly located in the nurse cells, which are actively
      supporting growth of the oocytes. On the basis of biochemical analyses ornithine
      decarboxylase has been considered mainly cytoplasmic in its distribution.
      However, in metabolically active polychaete cells (oocytes, nurse cells,
      intestinal and body wall cells), binding sites for tritiated DMFO, indicating the
      presence of active ornithine decarboxylase, were as abundant in the nucleus. The
      nucleolus was the most densely labeled organelle in nurse cells and oocytes.

PMID- 11596506
TI  - New patterns of nuclear lamina induced by cell fusion.
AB  - During the eukaryote cell cycle the nuclear envelope displays a series of major
      morphogenetic changes, the most significant of which include its breakdown and
      reconstitution as cells move up to, pass through and emerge from division. The
      three polypeptides, lamins A, B and C, are major components of the nuclear pore
      complex-lamina fraction of the nuclear envelope and their association with the
      nuclear membrane or their dispersal in the cytoplasm reflects the existing
      balance between polymerization and depolymerization in the envelope. We have
      perturbed the lamina polymerization cycle by means of cell fusion between mitotic
      and interphase cells, following the redistribution of nuclear lamina protein by
      means of immunofluorescence techniques. In these heterophasic heterokaryons
      changes in the distribution of lamina occur as a function of (1) the time elapsed
      after fusion; (2) the ratio of mitotic to interphase elements in the cell, and
      (3) the stage in the cell cycle occupied by the interphase partner at the time of
      fusion. Depolymerization of nuclear lamina occurs most rapidly in cells with high
      ratios of mitotic to interphase elements, and especially in G1 rather than S
      phase nuclei. While lamina depolymerization predominates early after fusion, at
      later times lamina is deposited around both the original metaphase and interphase
      nuclear masses and this is associated with the resumption of interphase activity
      in the form of limited DNA synthesis. These observations lead us to conclude that
      lamina depolymerization is under positive control mediated by diffusible factors
      in the cytoplasm of the metaphase partner. Repolymerization is likely to be
      associated with the inactivation of these factors as the heterokaryons age and,
      as a result, pass into an interphase-like state.

PMID- 11596508
TI  - In vitro microtubule assembly on centrioles from mammalian spermatids.
AB  - In the present study we have shown that the centriolar structures, which form the
      neck region of the spermatid tail, can act as microtubule-organizing centers.

PMID- 11596507
TI  - Molecular architecture of fungal cell walls. An approach by use of fluorescent
      markers.
AB  - Fluorescent probes have been applied to analyze the molecular architecture of
      fungal cell surfaces. Binding patterns of aniline blue and FITC-labeled wheat
      germ agglutinin (FITC-WGA) elucidated class-specific properties. Aniline-blue
      induced fluorescence was distributed over the entire cell walls from Ascomycetes,
      but was confined to sporangial walls of Zygomocetes, hyphal tips and a few other
      sites in Basidiomycetes, while no fluorescence was found with sporangia and
      rhizoids of Chytridiales. FITC-WGA in Zygomycetes and in Ascomycetes was
      restricted to few sites (e.g. apex of hyphae), in Basidiomycetes and Chytridiales
      label was evenly associated with the entire surface of hyphal walls, or sporangia
      and rhizoids. For Oomycetes, Zygomycetes, Ascomycetes, and Basidiomycetes
      differences in the molecular architecture between apex and hyphal side walls were
      discerned, although the chemical nature of these differences is distinct for each
      class. Species specific differences, due to differences in binding patterns of
      several lectins are not apparent at fungal cell surfaces. The degree of
      intraspecies variation was found to be larger than interspecies diversification,
      suggesting changeableness of the molecular architecture of fungal cell walls.
      This is in contrast to assertions which we made by working on algae. There
      species-specific lectin binding patterns have been described.

PMID- 11596509
TI  - Immunocytochemical study of the action of cis-dichlorodiamino platinum on the
      human metaphase chromosome.
AB  - The reaction of cis-dichlorodiamino platinum (cis-Pt) with the human metaphase
      chromosome was studied using both Giemsa staining and the action of anti-cis-Pt
      antibody. Two kinds of experiment were performed: (1) cis-Pt was placed in
      contact with cells in culture (in vivo tests), (2) cis-Pt was placed in contact
      with chromosomes fixed on slides (in vitro tests). In vivo, the presence of cis
      Pt during phase G1 of the cell cycle is important for the reaction; in vitro,
      competition between cis-Pt and Giemsa for fixation on chromosomal DNA was shown
      to occur.

PMID- 11596510
TI  - Regulation of differentiation in a variety of eukaryotic model systems.

PMID- 11596511
TI  - [Bronchoaveolar lavage for the diagnosis of lower airway disorders in horses].
AB  - Equine pulmonary disease and especially the terminology of lower airway disease
      have been subject to discussion. Besides established terms such as 'Chronic
      Obstructive Pulmonary Disease' (COPD) and Chronic bronchitis, the term 'small
      airway disease' (SAD) has been introduced, for respiratory disease with
      inflammation in the lower airways in combination with exercise intolerance.
      Bronchoalveolar lavage (BAL) enables the practitioner to diagnose SAD in an early
      stage when there are no other signs such as coughing or exudate in the trachea.
      The BAL fluid is microscopically examined after centrifugation. BAL cytology,
      especially neutrophilia, eosinophilia, and an increase in mast cells, is
      important, not only to decide whether SAD is present but also to determine in the
      choice of therapy.

PMID- 11596512
TI  - [Antimicrobial veterinary drugs in 1999 one third of the total antibiotic use in
      Europe. FIDIN (Manufacturers and Importers of Veterinary Drugs in the
      Netherlands) antibiotics report 2000].

PMID- 11596513
TI  - [The donkey, an animal full of contradictions].

PMID- 11596514
TI  - [Dutch BSE cases warrant genetic research].

PMID- 11596515
TI  - [The killing of aquarium fish by owners: a commentary].

PMID- 11596516
TI  - [Veterinarian as expert witness is legally responsible].

PMID- 11596517
TI  - [What is the efficacy of supplements against arthrosis and arthritis in animal
      feed].

PMID- 11596518
TI  - [Separating pets and farm animals 2].

PMID- 11596519
TI  - [Spoken by Dr. Poll].

PMID- 11596520
TI  - [Point of view of KNMvD concerning foot and mouth disease marker vaccine].

PMID- 11596521
TI  - Perspectives. Baby boom retirement puzzle has many moving parts.

PMID- 11596523
TI  - Corporate profile. Camtronics Medical Systems: leading cardiology integration.

PMID- 11596524
TI  - One Stop Post Op cardiac surgery recovery--a proven success.
AB  - The One Stop Post Op model for open heart surgery recovery is an innovative
      approach to post op care utilized in only a few facilities in the country. This
      model calls for an integration of acute ICU and step-down phases of care, thus
      changing the paradigm for nursing care of the open heart surgery patient.
      Typically, hospitals incur inefficiencies transferring the patient through
      multiple levels of care, thus resulting in a "disconnect" as new caregivers
      relearn the patient's care requirements and special needs. The construction of a
      "one stop" unit allows the patient to remain stationary while the service level
      changes to accommodate changing care needs. The cardiac "one stop" model is
      similar to the LDRP concept for obstetrical care. The One Stop Post Op patient
      rooms are designed to accommodate every level of patient acuity. All rooms meet
      the regulations for critical care room design, however this is where the
      aesthetic similarity ends. The patient environment looks more like hotel rooms
      rather than the traditional ICU setting. Cabinets designed to cover medical
      gases, in the room's private bathrooms and comfortable furnishings help to create
      a patient focused environment conducive to recovery. This model has been utilized
      by several facilities and has demonstrated clear clinical and economic advantages
      for patients, families, and health care providers. Implementing an open heart
      surgery (OHS) program presents the opportunity for several community based
      hospitals to challenge the way they have been providing patient care and
      establish an innovative approach to post surgery patient care. The One Stop Post
      Op cardiovascular recovery unit is designed to receive the OHS patient directly
      from the operating room and to be the "care unit" for the patient's entire stay.
      Patient flow, quality monitoring and caregiver acceptance in this unit requires
      new paradigms from the traditional two or three step post OHS care delivery
      process. The One Stop Post Op model focuses the delivery of care on the patient.
      With proven success in clinical outcomes, patient, physician and caregiver
      satisfaction, it is anticipated that this innovative approach will drive
      hospitals to integrate clinical process with physical planning in the future.

PMID- 11596522
TI  - Leading by consent.

PMID- 11596525
TI  - The not-so-dormant commerce clause: implications of the Quintiles-WebMD case for
      HIPAA preemption.

PMID- 11596526
TI  - Developing a vascular center to serve the community.

PMID- 11596527
TI  - The changing landscape: cardiac centers must adapt to new market conditions.

PMID- 11596528
TI  - A neurosurgeon's view on interventional neurophysiology.

PMID- 11596529
TI  - Botulinum toxin in motor disorders: practical considerations with emphasis on
      interventional neurophysiology.
AB  - After a brief review of the pharmacological properties of the botulinum toxin
      (BT), its mechanism of action on the nerve endings of the neuromuscular
      junctions, and the general therapeutic principles and adverse side effects, we
      discuss the advantages of interventional neurophysiology for the treatment of
      focal motor disorders by means of botulinum toxin A (BTA) muscle infiltration.
      Electromyography (EMG) provides a valuable objective information in the diagnosis
      of many motor disturbances and enables the precise identification of the muscles
      that contribute to the abnormal movement or posture. The use of EMG guidance for
      BTA injection seems advisable in every muscle but it become indispensable in
      those difficult to access, deeply located or partially atrophied by previous
      toxin infiltrations. The EMG study also serves to localise the areas with the
      highest abnormal activity and the motor point of the muscle, where the injection
      of toxin exerts its maximal effect. Consequently, lower doses of BTA can be
      employed without decreasing the efficacy of treatment but reducing the potential
      risk of side effects, antibody production and the cost of treatment.
      Electrophysiological diagnosis and BTA treatment may be performed during the same
      exploration. Considerations on the particular aspects and lines of action are
      given referring to the main focal muscular hyperactivity motor disorders such as
      cervical, oromandibular and laryngeal dystonias, blepharospasm, writer's cramp,
      hemifacial and hemimasticatory spasms, infantile and adult forms of spasticity
      and some other focal disturbances such as strabismus, detrusor-sphincter
      dyssynergia and anismus.

PMID- 11596530
TI  - Microelectrode recording and macrostimulation in thalamic and subthalamic MRI
      guided stereotactic surgery.
AB  - Stereotactic neurosurgery aims at placing therapeutic lesions or chronic
      stimulating electrodes at very precise locations within the brain. Microelectrode
      recording and macrostimulation are used in addition to anatomoradiological
      techniques to optimize targeting. Recently, the usefulness of
      electrophysiological procedures has been questioned. Based on more than 500
      therapeutic stereotactic lesions in the last 10 years at the thalamic and
      subthalamic levels, we evaluate here retrospectively the utility of the two
      electrophysiological procedures. In two of the three stereotactic targets
      considered in this study, intraoperative electrophysiological confirmation is
      mandatory because of the target size with respect to interindividual anatomical
      variations and of the more or less close vicinity of eloquent structures.

PMID- 11596531
TI  - Interventional neurophysiology of the sacral nervous system.
AB  - Clinical neurophysiological tests have been introduced for the sacral
      neuromuscular system to aid with diagnosis of neurogenic conditions involving the
      lower urinary tract, anorectal and sexual dysfunction. The tests have, however,
      the potential to be of value in different interventions outside of the
      neurophysiological laboratory. EMG monitoring can be used for exact application
      of botulinum toxin by the relatively non-invasive transcutaneous approach in
      treatment of male detrusor sphincter dyssynergia. Checking for compound muscle
      action potentials of the external anal sphincter is proposed as the best method
      for exact placement of wire electrodes close to the 3rd sacral roots in treating
      lower urinary tract dysfunction by 'neuromodulation'. Presently the most
      established use of clinical neurophysiological techniques--outside the laboratory
      -as related to the sacral neuromuscular system is in the operating theatre. These
      tests have been introduced to identify relevant structures, for instance pudendal
      afferents within dorsal sacral roots, which should be spared during rhizotomy
      procedures for treatment of spasticity. Modified techniques are used
      intraoperatively to monitor the integrity of the lower sacral reflex arc (the
      bulbocavernosus reflex) or the lower sacral afferents throughout the spinal cord
      (pudendal SEP). Clinical neurophysiological tests are expected to become
      established in several interventions involving the sacral neuromuscular system.

PMID- 11596532
TI  - Event-related potentials, CNV, readiness potential, and movement accompanying
      potential recorded from posterior thalamus in human subjects. A SEEG study.
AB  - Intracranial recordings were obtained from three patients with intractable
      chronic pain who underwent analgesic electrical stimulation of the contralateral
      thalamus. Multilead electrode made it possible to record from several thalamic
      nuclei. The electrode was targeted into the ventroposterolateral (VPL) nucleus of
      the thalamus. During separate recording sessions, the following tests were
      performed: somatosensory evoked potentials (SEP) of the median or posterior
      tibial nerve, event-related cognitive potentials (auditory oddball P3 wave),
      readiness potential (RP) and contingent negative variation (CNV) using auditory
      warning (S1) and visual imperative (S2) stimuli. The movement accompanying
      potential (MAP), which was present in the VPL in all but one of the recordings,
      behaved as a far-field potential. Recordings obtained from the VPL confirmed its
      established role as a relay nucleus, processing somatosensory information to the
      primary somatosensory cortex. The VPL generated the 'thalamic' SEP, which was the
      only potential regularly recorded in this nucleus. In the recordings from one
      patient (No. 3), auditory and visual evoked potentials of the CNV protocol,
      peaking at approximately 300 ms, were obtained from the VPL and appeared to be
      generated in situ. Neither RP, CNV nor 'oddball' ERPs appeared in the VPL. From
      the pulvinar, only a visually evoked potential was recorded. Oddball P3, RP, CNV,
      and middle and long latency auditory and visual potentials (evoked in the CNV
      paradigm) appeared to be generated 'dorsally' to the VPL, probably in the nucleus
      posterolateralis (PL). This structure may therefore be involved in both the
      processing of afferent information and in cognitive operations.

PMID- 11596533
TI  - [Human health aspects of antibiotic use in food animals: a review].
AB  - Antibiotic use not only selects for resistance in pathogenic bacteria, but also
      in the commensal flora of exposed individuals. Veterinary surgeons regularly
      prescribe antibiotics for food animals to treat bacterial infections just as
      doctors do for human patients. In addition, however, animal feeds contain added
      antibiotics not for therapy but for economic reasons: to enhance the growth rate
      of these animals. Several of the antibiotics used as growth promoters are
      analogues of and fully cross resistant with important antibiotics used in human
      medicine. As a result of this high exposure to antibiotics, the prevalence of
      resistant bacteria in the faecal flora of these animals is high. These resistant
      bacteria can be directly and indirectly, via foods of animal origin, transferred
      to humans and either colonize the human intestinal tract or exchange their
      resistance genes with commensal bacteria of humans. As the intestinal flora
      functions as a reservoir of resistance genes for pathogenic bacteria and because
      many bacterial species of the intestinal flora are potential pathogens, the
      efficacy of antibiotic therapy in human medicine may be jeopardized.

PMID- 11596534
TI  - [Incomplete diagnosis].

PMID- 11596535
TI  - [High amylase level in a vomiting dog or cat].

PMID- 11596536
TI  - [Round table discussion about foot and mouth disease prevention and control. The
      goals and differences of opinion on how to get there].

PMID- 11596537
TI  - [Clinical practice certification].

PMID- 11596538
TI  - [Overturn of the Society of Veterinarians. Animal or thing?].

PMID- 11596539
TI  - [Yearly report Ereraad 2000. More complaints, less arbitration].

PMID- 11596540
TI  - The growth of hospital-based palliative care.

PMID- 11596541
TI  - Survey of palliative care programs in United States teaching hospitals.
AB  - In order to estimate the prevalence of palliative care programs in academic
      hospitals in the United States, we surveyed a random sample of 100 hospitals in
      the Council of Teaching Hospitals and Health Systems directory. Sixty percent of
      hospitals provided information. At least 26% of hospitals had either a palliative
      care consultation service or inpatient unit and 7% had both. Eighteen percent of
      hospitals had a palliative care consultation service alone, 19% had an inpatient
      palliative care unit, 22% reported a hospice affiliation, and 17% had a hospice
      inpatient contract. Additionally, at least 20% of the remaining hospitals were
      planning a palliative care program. The consultation services had an average
      daily census of 6; the inpatient units had an average of 12 beds. Palliative care
      consultation programs were largely affiliated with departments of medicine or
      hematology/oncology, and were typically staffed by a physician and a nurse. Only
      half had a dedicated social worker, one third had a chaplain, one third had a
      pharmacist, and a few included a bereavement coordinator or volunteer director,
      suggesting that the hospice model of interdisciplinary care is not being adopted
      regularly in palliative care programs. In comparison, almost half of hospitals
      noted established pain services. In conclusion, palliative care programs,
      although found in a minority of surveyed hospitals, are becoming an established
      feature of academic medical centers in the United States. More detailed
      information is needed about the type and quality of care they provide.

PMID- 11596543
TI  - Patients with eventually fatal chronic illness: their importance within a
      national research agenda on improving patient safety and reducing medical errors.
AB  - In September 2000, the Quality Interagency Coordination (QuIC) Task Force invited
      the RAND Center to Improve Care of the Dying and Americans for Better Care of the
      Dying to testify at its National Summit on Medical Errors and Patient Safety
      Research. In their testimony, the organizations urged the QuIC to consider the
      special vulnerability and needs of individuals at the end of life in crafting
      their research agenda. Patients at the end of life are particularly vulnerable to
      medical errors and other lapses in patient safety for three reasons: (1)
      substantially increased exposure to medical errors; (2) more serious effects from
      errors because they cannot protect themselves from risks and have less reserve
      with which to overcome the effects; and (3) pervasive patterns of care that run
      counter to well-substantiated evidence-based practices. A national research
      agenda on preventing medical errors and increasing patient safety must include a
      focus on how to improve shortcomings affecting these vulnerable patients. The
      QuIC's preliminary research agenda, released in October 2000, included patients
      coming to the end of life. The Agency for Healthcare Research and Quality, the
      lead federal agency for researching patient safety and medical errors, released
      between November 2000 and April 2001 six Requests for Applications for research
      into medical errors.

PMID- 11596542
TI  - How prevalent are hospital-based palliative care programs? Status report and
      future directions.
AB  - In the United States, the majority of deaths occur in the hospital but the dying
      process there is at best unsatisfactory and more likely inadequate for both
      patients and caregivers. The development of hospital-based palliative care
      programs (HBPCPs) can vastly improve inpatient end-of-life care. This study is
      the first to examine the prevalence and characteristics of HBPCPs in the United
      States, thus providing a snapshot of the characteristics of these HBPCPs. It also
      serves as a baseline and benchmark against which future development and patterns
      of HBPCPs can be compared. Phase 1: Data were obtained from the American Hospital
      Association (AHA) 1998 Annual Survey, on the existence of end-of-life care (EOLC)
      and pain management (PM) services in U.S. hospitals. Phase 2: A focused survey
      further assessed programs in Phase 1 and was sent to all registered hospitals
      that responded affirmatively to the AHA survey questions as having either a PM
      service, an EOLC service, or both. In phase 1, 1,751 (36%) hospitals reported
      having a PM service and 719 (15%) had an EOLC service, for a total of 2,015
      unique hospitals that had one or both. For Phase 2, 1,120 of 2,015 responded
      (56%). Of these, 337 (30%) hospitals reported having an HBPCP, and another 228
      (20.4%) had plans to establish one. HBPCPs are most commonly structured as
      inpatient consultation service and hospital-based hospice. They tend to be based
      in oncology, general medicine, and geriatrics. We also assessed reasons for
      consultation, patient characteristics, and future development needs. These
      findings can help guide future funding, educational, and programming efforts in
      hospital-based palliative care.

PMID- 11596544
TI  - Spirituality and religion in end-of-life care.

PMID- 11596545
TI  - Senior medical students' perceptions of the adequacy of education on end-of-life
      issues.
AB  - CONTEXT: It is unclear how well prepared U.S. senior medical students are to
      handle end-of-life issues as they reach the end of medical school. Additionally,
      the most optimal way of providing medical student end-of-life education has not
      been adequately defined. OBJECTIVE: This study aims to determine the preparedness
      of senior medical students at U.S. medical schools regarding end-of-life issues.
      DESIGN: A self-administered survey. SETTING: Six medical schools throughout the
      United States, two of which have a formal curriculum on end-of-life issues, and
      four of which do not. PARTICIPANTS: Fourth-year medical students during November
      through February of their senior year. MAIN OUTCOME MEASURE: Self-reported
      preparation on a number of end-of-life competencies. RESULTS: Of the 757 surveys
      sent out, 262 responses were received (34.6%). Only 22% to 53% of students
      (varying by topic) felt prepared by their education in the selected end-of-life
      competencies. Students attending medical schools with a formal end-of-life
      curriculum were more likely to feel prepared than students with no formal
      curriculum to address psychosocial issues (21% higher, p = 0.008),
      cultural/spiritual issues (21% higher, p = 0.005), technical aspects of end-of
      life care (18% higher, p = 0.001), and treatment of common symptoms (34% higher,
      p = 0.001). Students who had more clinical experiences in palliative care were
      more likely to feel prepared to discuss end-of-life issues with patients (p =
      0.013) and to treat common symptoms (p = 0.011). CONCLUSIONS: This study
      demonstrates support for development of formal curriculum on end-of-life issues,
      and emphasizes the importance of clinical exposure to terminally ill patients to
      prepare medical students to provide quality end-of-life care.

PMID- 11596546
TI  - Serendipitous ripples: unexpected outcomes of a palliative care educational
      project.
AB  - The Institute of Palliative Care in Ottawa, Canada, began its continuing
      education programs in 1994. Since 1997, the Institute has been developing and
      delivering a community-based, interdisciplinary palliative care educational
      program in each of the three regions of its jurisdiction. Members of the local
      communities work in active partnership with the faculty in the planning,
      implementation, and delivery of the programs. The comprehensive evaluation
      strategy includes a component referred to as "serendipitous ripples." These are
      outcomes that resulted directly from the programs, but were not anticipated.
      These outcomes reflect impacts on individuals and groups across the three regions
      and represent some significant impacts in the communities that should improve
      care of the terminally ill.

PMID- 11596547
TI  - Religion, medicine, and community in the early origins of St. Christopher's
      Hospice.
AB  - Commentators on the history and development of hospice and palliative care can
      appear inclined toward a revisionist viewpoint that sees something "lost" in
      recent years from the original concept. The thesis concerning the "secularization
      of hospice" is one such example. It is suggested that the quality of these
      debates can be improved by serious scholarly attention to earlier events and
      circumstances, drawing on contemporary source materials, rather than
      retrospective viewpoints. This article, based mainly on correspondence from the
      early 1960s, explores ideas that shaped the early origins of St. Christopher's
      Hospice, England. It shows how Cicely Saunders and her associates created an Aim
      and Basis for the hospice that sought to reconcile questions about its religious
      orientation; its relationship to medicine; and its status as a community. We see
      how tensions between these were resolved, resulting in a model that would be
      applicable in other contexts. Without this pragmatic turn, it is unlikely that
      the hospice movement would have spread so quickly and so far in the 1970s and
      1980s.

PMID- 11596549
TI  - Reflecting on the work of palliative care.
AB  - Caring for the terminally ill and their families is a unique experience. The
      experiences of our everyday work shape and transform us as individuals and as
      teams in ways that are sometimes subtle and unrecognizable and other times quite
      overt and apparent. Yet some of us as palliative care professional caregivers
      seldom take the time to stop and reflect on the work we do and how it impacts us,
      both personally and collectively as a team. In this article we share our
      experiences with a multidisciplinary "Reflection" Group.

PMID- 11596548
TI  - The role of palliative care in the home in medical education: report from a
      national consensus Conference.
AB  - A working group on teaching palliative care in the home was convened at The
      National Consensus Conference on Medical Education for Care Near the End of Life.
      Our consensus statement includes: (1) a justification for education in the home;
      (2) general guidelines about teaching palliative care at this site; (3)
      identification of major barriers to training in the home, and some suggestions
      for overcoming these barriers; and (4) specific suggestions about how and what to
      teach. We find that the home is an excellent site for training in comprehensive
      palliative medicine. Housecalls afford an unusually rich and compelling
      opportunity to learn about the patient's and family's experience of severe
      illness and the impact of culture and environment on health care, and can have a
      broad humanizing effect on trainees. We propose that all medical students be
      familiar with this form of care. Trainees should learn the potential benefits and
      difficulties of managing terminal illness in the community, appreciate the role
      of health care teams in assuring safe, secure, high-quality care, and acquire the
      special knowledge, skills, and attitudes required for providing state-of-the-art
      palliative care for patients and families facing a terminal illness in the home,
      including for those dying at home. Instituting education in the home setting will
      require faculty development, support for more home visiting by physicians, and
      supervision of trainees in the home by other members of the health care team.
      Academic medical centers and hospice/home health agencies should collaborate to
      develop effective training programs.

PMID- 11596550
TI  - Sociodrama: a teaching method for expanding the understanding of clinical issues.
AB  - Sociodrama is a powerful teaching strategy that combines a case study approach
      with traditional role-play methodology to illustrate critical issues in end-of
      life care. Building on principles of adult learning and communication skills, the
      sociodrama method enables the skilled facilitator to draw on the learner's past
      experiences as resources for teaching and reflective practice. This article
      describes the use of sociodrama in end-of-life education with illustrations from
      actual sessions including key discussion points, a typical instructional plan and
      staging tips.

PMID- 11596551
TI  - Abdominal cancer, nausea, and vomiting.
AB  - Nausea and vomiting in abdominal cancer is perhaps one of the most difficult
      symptom complexes to manage, especially when complicated by bowel obstruction.
      There are many mechanisms of nausea in advanced abdominal cancer with a number of
      therapeutic interventions that can significantly enhance symptom control and
      overall quality of life. As with pain, the ideal approach should include a
      mechanistic analysis of the causes of nausea beginning with a thorough history,
      followed by a directed physical examination, and selected laboratory studies. The
      symptom history, in conjunction with a physical examination and directed tests
      should direct appropriate pharmacologic and nonpharmacologic interventions. The
      result is often the amelioration of significant suffering and enhanced quality of
      living.

PMID- 11596552
TI  - Politics, palliation, and Canadian progress in end-of-life care.
AB  - How do health care consumers, private sector organizations, professionals, and
      government agencies work toward ensuring quality end-of-life care? This challenge
      is by no means uniquely Canadian; our approach may thus have applications that
      extend well beyond our national borders. Raising the profile of palliative care
      in Canada has occurred on many fronts. Local, provincial, and national efforts in
      end-of-life care have long been underway. The Canadian Palliative Care
      Association has been particularly active, recently organizing various stakeholder
      groups to develop a strong national advocacy partnership for quality end-of-life
      care. Perhaps most distinctive has been the involvement and nationwide visibility
      of Canada's Senate. Their report, Quality End-of-Life Care: The Right of Every
      Canadian has seen Canadian palliative care gain unprecedented momentum. The
      federal government recently took the unprecedented step of creating a new office
      to represent palliative care within the federal cabinet. In Canada, it would
      appear that palliative care is an idea whose time has come.

PMID- 11596553
TI  - Assessment of quality of life in palliative care.

PMID- 11596554
TI  - Addressing quality of life at the Edmonton Palliative Care Program. Interview by
      Anna L. Romer.

PMID- 11596555
TI  - Promoting quality of life near the end of life in Argentina. Interview by Karen
      S. Heller.

PMID- 11596556
TI  - The demand for child curative care in two rural thanas of Bangladesh: effect of
      income and women's employment.
AB  - This paper seeks to investigate the determinants of child health care seeking
      behaviours in rural Bangladesh. In particular, the effects of income, women's
      access to income, and the prices of obtaining child health care are examined.
      Data on the use of child curative care were collected in two rural areas of
      Bangladesh--Abhoynagar Thana of Jessore District and Mirsarai Thana of Chittagong
      District--in March 1997. In estimating the use of child curative care, the nested
      multinomial logit specification was used. The results of the analysis indicate
      that a woman's involvement in a credit union or income generation affected the
      likelihood that curative child care was used. Household wealth decreased the
      likelihood that the child had an illness episode and affected the likelihood that
      curative child care was sought. Among facility characteristics, travel time was
      statistically significant and was negatively associated with the use of a
      provider.

PMID- 11596557
TI  - Improving performance with clinical standards: the impact of feedback on
      compliance with the integrated management of childhood illness algorithm in
      Niger, West Africa.
AB  - The joint BASICS/Quality Assurance Project tested several research-based
      interventions in three districts in Niger, West Africa to improve case management
      of sick children. The research design was a non-concurrent, prospective case
      control design. Quality of care was determined as the degree of compliance of
      health care workers with the Integrated Management of Childhood Illness (IMCI)
      standards of assessment, treatment and counselling of sick children and their
      caretakers. The interventions tested were (1) structured feedback of health
      worker performance data and (2) formal IMCI training and (3) team-based quality
      improvement. Performance feedback had a significant effect on compliance.
      Performance feedback alone created a significant short-term impact on health care
      worker compliance, which improved between 34% and 85% in areas of assessment of
      sick children (p < 0.05). In addition, performance feedback was significantly
      cheaper than formal training ($108 per health worker versus $430 per worker for
      IMCI training). However, this impact was not universal over all areas of
      compliance following each feedback. Instead, performance feedback had the
      greatest effect in areas in which health care workers performed poorly, while
      areas in which compliance was high eventually saw declines. In settings such as
      Niger, which has the highest child mortality in the world according to UNICEF
      figures, low-cost techniques for supporting health workers once they have been
      trained in clinical standards are sorely needed. Performance feedback shows
      promise as a technique for improving quality of care with clinical algorithms
      such as IMCI.

PMID- 11596558
TI  - Beyond health care cost containment: creating collaborative arrangements among
      the stakeholders.
AB  - The causes of escalating healthcare costs in the United States and many other
      industrial countries are well documented. Less evident are the structural factors
      that underlie the increases and their implications for the future. This paper
      discusses these structural factors, puts them in the context of the healthcare
      marketplace, and proposes a way to address them using a collaborative arrangement
      among all stakeholders in a healthcare system, called value-based partnering. To
      be successful, the effort must include not only final purchasers (such as
      employers or Medicare in the USA) but all stakeholders in a healthcare system.
      Each stakeholder must develop a value equation in terms that are meaningful to
      the others, and must identify opportunities for value-enhancing partnerships. The
      paper also identifies some of the impediments to value-based partnering and
      discusses ways to overcome them, including the need for senior management
      intervention within some stakeholder groups, and the importance of collaborative
      discussions among all stakeholders.

PMID- 11596559
TI  - Quality evaluation and indicator comparison in health care.
AB  - By 2005 all healthcare organizations in Europe will be required to take part in a
      quality evaluation scheme and to collect data about the quality of their service.
      Hospitals and doctors will need to prove they are safe--quality is no longer
      assumed. These were the predictions of a recent workshop of Nordic quality
      experts. The pressures to assess quality are increasing, and there are many
      assessment, certification, accreditation and measurement schemes in use. Which is
      best? What evidence is there that any have been effective? How should a hospital
      or region introduce such a scheme? There are many proponents for different
      schemes, and an increasing amount of experience to help answer these questions,
      but little research. This paper provides an overview for non-specialists of the
      different quality evaluation and indicator schemes for inspection and
      improvement. It draws on the experiences of quality specialists and leaders in
      each Nordic country who have applied the schemes in public hospitals and
      healthcare services. How a scheme is introduced and used may be more important
      than which particular scheme is chosen. This is one conclusion of the Nordic
      workshop. Other conclusions are that there is a need for clinicians to be
      involved, a need to balance simplicity and low cost with scientific validity and
      credibility with clinicians, and a need for research into different schemes to
      discover their costs and benefits in healthcare.

PMID- 11596560
TI  - Patient referral patterns in Namibia: identification of potential to improve the
      efficiency of the health care system.
AB  - In order to assess how the hospital referral system in Namibia was operating, a
      cross-sectional survey of patients attending three intermediate hospitals and the
      national hospital was conducted over a 4-week period. The survey was planned by a
      Ministry of Health and Social Services' working group, with technical support
      provided by a donor funded health programme. Together with complementary
      qualitative data, obtained through focus group discussions with the community,
      the survey generated information on the extent to which the referral system was
      being bypassed, the types of bypassing and related factors. These included
      reasons for non-compliance with referral to the intermediate hospitals, perceived
      barriers to their utilization and community preparedness to use these hospitals
      after upgrading. The results were used to inform decisions about the
      classification of the three hospitals and identification of their catchment
      areas. The results were also shown to be useful for assessing the likely impact
      of different strategies for reducing bypassing. In Namibia these impacts were
      expected to be limited, due to the influence of distance and low population
      densities. Information on the extent and types of bypassing taking place across
      districts is essential for assessing opportunities to improve the functioning of
      a pyramidal referral system, which supports a cost-effective primary health care
      strategy.

PMID- 11596561
TI  - Financing indicators for health care decentralization in Latin America:
      information and suggestions for health planning.
AB  - This article presents the results from an evaluative longitudinal study with
      before-after design. The main objective was to determine the effects of health
      care decentralization on changes in health financing. Taking into account
      feasibility, political and technical criteria, three Latin American countries
      were selected as study populations: Mexico, Nicaragua and Peru. The methodology
      had two main phases. In the first phase, the study referred to secondary sources
      of data and documents to obtain information about the following variables: type
      of decentralization implemented, source of finance, funds of financing,
      providers, final use of resources and mechanisms for resource allocation. In the
      second phase, the study referred to primary data collected in a survey of key
      personnel from the health sectors of each country. Taking into account the
      changes implemented in the three countries, as well as the strengths and
      weaknesses of each country in financing and decentralization, a rule for decision
      making is proposed that attempts to identify the main financial changes
      implemented in each country and the basic indicators that can be used in future
      years to direct the planning, assessment, adjustment and correction of health
      financing and decentralization.

PMID- 11596562
TI  - [Physiopathology of lymphatic metastasis and lymph node dissection].

PMID- 11596563
TI  - Inconclusive HIV-1/2 results: how far should blood centers go?

PMID- 11596564
TI  - The Evolution of Developmental Mechanisms. Proceedings of a symposium. London,
      United Kingdom, January 2001.
AB  - In 1829, von Baer proposed four principles of development, the first of which
      states that the embryos of a large group of animals have most in common at early
      stages of development, the specialised features of different subgroups only
      emerging later. After the publication of Darwin's The Origin of Species in 1859,
      the relevance of von Baer's principles to evolution was clear to many biologists,
      who assessed evolutionary relationships on the basis of similarities and
      differences between early embryos. The validity of these comparisons, carried out
      more than a century ago, has been confirmed by recent molecular analyses. These
      new gene-based comparisons have in turn led to a renewed interest in the
      scientific literature of the first half of the 20th century, which documented in
      great detail comparative anatomical studies of living and fossil animals. The
      past decade has seen a growing synergy between developmental biology and
      evolutionary studies. As a result, not only is an evolutionary perspective now
      integral to developmental studies, but palaeontologists have become deeply
      interested in embryos. This integration was the subject of the symposium of the
      Winter Meeting of the Anatomical Society, held in London in January 2001,
      entitled 'The Evolution of Developmental Mechanisms'. It was a very stimulating
      and enjoyable meeting that addressed the theme at a number of levels, ranging
      from the major evolutionary changes resulting from gene duplication to the fine
      detail of insect wing vein evolution. These two ends of the spectrum of topics
      reflect Darwin's perspective on von Baer's principles, i.e. his recognition that
      homologies between different phyla are to be seen in early embryonic and larval
      structures, while adaptations that enable an organism to survive in its
      particular environment are the result of changes acting late in development. The
      reviews brought together in this volume represent a thoughtful and thought
      provoking synthesis of data collected over many years. They show the rewards of
      detailed and long-term study of embryos that in some cases are difficult to
      obtain, but represent living clues to the mechanisms underlying important
      evolutionary transitions. We feel privileged to have had the responsibility for
      editing this impressive issue of the Journal of Anatomy, which will, we have no
      doubt, be a significant landmark in the ongoing story of development and
      evolution, and will be widely cited.

PMID- 11596565
TI  - Positive neuropathic sensory symptoms as endpoints in diabetic neuropathy trials.

PMID- 11596566
TI  - Vibration during high frequency ventilation in neonates.

PMID- 11596567
TI  - National survey of detention and TB.

PMID- 11596568
TI  - Churg-Strauss syndrome.

PMID- 11596569
TI  - Acute rib fracture pain in CF.

PMID- 11596570
TI  - Endothelin in acute exacerbations of COPD.

PMID- 11596571
TI  - CF and antistaphylococcal prophylaxis.

PMID- 11596572
TI  - High-dose cyclophosphamide to treat severe aplastic anemia.

PMID- 11596573
TI  - Determinants of vancomycin resistance and death in enterococcal bacteremia.

PMID- 11596574
TI  - Hormone replacement therapy in postmenopausal women with heart disease and risk
      for gallstones that require surgery.

PMID- 11596575
TI  - Delayed-onset heparin-induced thrombocytopenia and thrombosis.

PMID- 11596576
TI  - The state of the health care workforce.
AB  - The shortage of health care workers has emerged as one of the field's biggest
      long-term challenges. The number of nurses, technicians, pharmacists and even
      housekeeping staff is on the way down, and worker dissatisfaction is on the way
      up. The health care workforce is slowly vanishing, and those workers who remain
      are unhappy. In this special fold-out section, Hospitals & Health Networks looks
      at this complex problem by analyzing how serious it really is and how bad it's
      going to get, taking a look at workers' frustration, and offering tips and
      resources to start to fix it.

PMID- 11596577
TI  - Bilateral circumscribed haemangioma of the choroid not associated with systemic
      vascular syndrome.

PMID- 11596578
TI  - Tractional ciliary body detachment, choroidal effusion, and hypotony caused by
      severe anterior lens capsule contraction following cataract surgery.

PMID- 11596579
TI  - Angle closure in fellow eye with prophylactic pilocarpine treatment.

PMID- 11596580
TI  - Keratolysis in a patient with pemphigus vulgaris.

PMID- 11596581
TI  - Isolated episcleral plasmacytoma mimicking episcleritis in a patient with benign
      monoclonal gammopathy.

PMID- 11596582
TI  - Crystalluria with sulphadiazine.

PMID- 11596583
TI  - Ocular involvement caused by the accumulation of porphyrins in a patient with
      congenital erythropoietic porphyria.

PMID- 11596584
TI  - Bilateral facial nerve palsy associated with p-ANCA positive vasculitis in a
      patient with rheumatoid arthritis.

PMID- 11596585
TI  - Bilateral conjunctival lesions in Melkersson-Rosenthal syndrome.

PMID- 11596586
TI  - Patients at high risk of death after lung-volume-reduction surgery.
AB  - BACKGROUND: Lung-volume-reduction surgery is a proposed treatment for emphysema,
      but optimal selection criteria have not been defined. The National Emphysema
      Treatment Trial is a randomized, multicenter clinical trial comparing lung-volume
      reduction surgery with medical treatment. METHODS: After evaluation and pulmonary
      rehabilitation, we randomly assigned patients to undergo lung-volume-reduction
      surgery or receive medical treatment. Outcomes were monitored by an independent
      data and safety monitoring board. RESULTS: A total of 1033 patients had been
      randomized by June 2001. For 69 patients who had a forced expiratory volume in
      one second (FEV1) that was no more than 20 percent of their predicted value and
      either a homogeneous distribution of emphysema on computed tomography or a carbon
      monoxide diffusing capacity that was no more than 20 percent of their predicted
      value, the 30-day mortality rate after surgery was 16 percent (95 percent
      confidence interval, 8.2 to 26.7 percent), as compared with a rate of 0 percent
      among 70 medically treated patients (P<0.001). Among these high-risk patients,
      the overall mortality rate was higher in surgical patients than medical patients
      (0.43 deaths per person-year vs. 0.11 deaths per person-year; relative risk, 3.9;
      95 percent confidence interval, 1.9 to 9.0). As compared with medically treated
      patients, survivors of surgery had small improvements at six months in the
      maximal workload (P= 0.06), the distance walked in six minutes (P=0.03), and FEV1
      (P<0.001), but a similar health-related quality of life. The results of the
      analysis of functional outcomes for all patients, which accounted for deaths and
      missing data, did not favor either treatment. CONCLUSIONS: Caution is warranted
      in the use of lung-volume-reduction surgery in patients with emphysema who have a
      low FEV1 and either homogeneous emphysema or a very low carbon monoxide diffusing
      capacity. These patients are at high risk for death after surgery and also are
      unlikely to benefit from the surgery.

PMID- 11596587
TI  - Prognosis after transient monocular blindness associated with carotid-artery
      stenosis.
AB  - BACKGROUND: Transient monocular blindness associated with internal-carotid-artery
      stenosis is a risk factor for stroke. The effect of carotid endarterectomy in
      patients who present with transient monocular blindness has not been determined.
      METHODS: We compared the risk of stroke among patients presenting with transient
      monocular blindness with the risk among patients presenting with hemispheric
      transient ischemic attack. The effect of endarterectomy was assessed in patients
      with transient monocular blindness. The analyses were based on data from the
      North American Symptomatic Carotid Endarterectomy Trial. RESULTS: A total of 198
      medically treated patients with transient monocular blindness had a three-year
      risk of ipsilateral stroke that was approximately half of that among 417
      medically treated patients with hemispheric transient ischemic attack (adjusted
      hazard ratio, 0.53; 95 percent confidence interval, 0.30 to 0.94). Six factors
      were associated with a higher risk of stroke in patients with monocular blindness
      -an age of 75 years or more, male sex, a history of hemispheric transient
      ischemic attack or stroke, a history of intermittent claudication, stenosis of 80
      to 94 percent of the luminal diameter, and the absence of collateral circulation.
      The three-year risk of stroke with medical treatment for patients with zero or
      one risk factor was 1.8 percent, with two risk factors 12.3 percent, and with
      three or more risk factors 24.2 percent (P=0.003). The three-year absolute
      reduction in the risk of stroke associated with endarterectomy was -2.2 percent
      (i.e., a 2.2 percent increase in risk) among patients with zero or one risk
      factor, 4.9 percent among those with two risk factors, and 14.3 percent among
      those with three or more risk factors (P=0.23 by a test for interaction).
      CONCLUSIONS: Among patients with internal-carotidartery stenosis, the prognosis
      was better for those presenting with transient monocular blindness than for those
      presenting with hemispheric transient ischemic attack. Among patients with
      transient monocular blindness, carotid endarterectomy may be beneficial when
      other risk factors for stroke are also present.

PMID- 11596588
TI  - A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly
      patients.
AB  - BACKGROUND: Adjuvant chemotherapy is standard treatment for patients with
      resected colon cancer who are at high risk for recurrence, but the efficacy and
      toxicity of such treatment in patients more than 70 years of age are
      controversial. METHODS: We performed a pooled analysis, based on the intention to
      treat, of individual patient data from seven phase 3 randomized trials (involving
      3351 patients) in which the effects of postoperative fluorouracil plus leucovorin
      (five trials) or fluorouracil plus levamisole (two trials) were compared with the
      effects of surgery alone in patients with stage II or III colon cancer. The
      patients were grouped into four age categories of equal size, and analyses were
      repeated with 10-year age ranges (< or =50, 51 to 60, 61 to 70, and >70 years),
      with the same conclusions. The toxic effects measured in all trials were nausea
      or vomiting, diarrhea, stomatitis, and leukopenia. Patients in the fluorouracil
      plus-leucovorin and fluorouracil-plus-levamisole groups were combined for the
      efficacy analysis but kept separate for toxicity analyses. RESULTS: Adjuvant
      treatment had a significant positive effect on both overall survival and time to
      tumor recurrence (P<0.001 for each, with hazard ratios of death and recurrence of
      0.76 [95 percent confidence interval, 0.68 to 0.85] and 0.68 [95 percent
      confidence interval, 0.60 to 0.76], respectively). The five-year overall survival
      was 71 percent for those who received adjuvant therapy, as compared with 64
      percent for those untreated. No significant interaction was observed between age
      and the efficacy of treatment. The incidence of toxic effects was not increased
      among the elderly (age >70 years), except for leukopenia in one study.
      CONCLUSIONS: Selected elderly patients with colon cancer can receive the same
      benefit from fluorouracil-based adjuvant therapy as their younger counterparts,
      without a significant increase in toxic effects.

PMID- 11596590
TI  - Images in clinical medicine. Hemorrhagic transformation of a cerebral infarct.

PMID- 11596589
TI  - Tuberculosis associated with infliximab, a tumor necrosis factor alpha
      neutralizing agent.
AB  - BACKGROUND: Infliximab is a humanized antibody against tumor necrosis factor
      alpha (TNF-alpha) that is used in the treatment of Crohn's disease and rheumatoid
      arthritis. Approximately 147,000 patients throughout the world have received
      infliximab. Excess TNF-alpha in association with tuberculosis may cause weight
      loss and night sweats, yet in animal models it has a protective role in the host
      response to tuberculosis. There is no direct evidence of a protective role of TNF
      alpha in patients with tuberculosis. METHODS: We analyzed all reports of
      tuberculosis after infliximab therapy that had been received as of May 29, 2001,
      through the MedWatch spontaneous reporting system of the Food and Drug
      Administration. RESULTS: There were 70 reported cases of tuberculosis after
      treatment with infliximab, for a median of 12 weeks. In 48 patients, tuberculosis
      developed after three or fewer infusions. Forty of the patients had
      extrapulmonary disease (17 had disseminated disease, 11 lymph node disease, 4
      peritoneal disease, 2 pleural disease, and 1 each meningeal, enteric,
      paravertebral, bone, genital, and bladder disease). The diagnosis was confirmed
      by a biopsy in 33 patients. Of the 70 reports, 64 were from countries with a low
      incidence of tuberculosis. The reported frequency of tuberculosis in association
      with infliximab therapy was much higher than the reported frequency of other
      opportunistic infections associated with this drug. In addition, the rate of
      reported cases of tuberculosis among patients treated with infliximab was higher
      than the available background rates. CONCLUSIONS: Active tuberculosis may develop
      soon after the initiation of treatment with infliximab. Before prescribing the
      drug, physicians should screen patients for latent tuberculosis infection or
      disease.

PMID- 11596591
TI  - Lack of health insurance and decline in overall health in late middle age.
AB  - BACKGROUND: The number of adults in their 50s and 60s in the United States who do
      not have health insurance is increasing. This group may be particularly
      vulnerable to the ill effects of being uninsured. METHODS: We conducted a
      prospective cohort study using files from the Health and Retirement Study, a
      national survey of adults who were 51 to 61 years old in 1992. We determined the
      risks of a major decline in overall health and of the development of new physical
      difficulties between 1992 and 1996 for participants who were continuously
      uninsured (uninsured in 1992 and in 1994), those who were intermittently
      uninsured (uninsured either in 1992 or in 1994), and those who were continuously
      insured. We used logistic regression to determine the independent effects of
      being uninsured on health outcomes after adjustment for base-line
      sociodemographic factors, preexisting medical conditions, and types of health
      related behavior such as smoking and alcohol use. RESULTS: We analyzed data for
      7577 participants. The 717 continuously uninsured participants and the 825
      intermittently uninsured participants were more likely than the 6035 continuously
      insured participants to have a major decline in overall health between 1992 and
      1996 (21.6 percent, 16.1 percent, and 8.3 percent of the three groups,
      respectively; P<0.001 for both comparisons). According to a multivariate
      analysis, the adjusted relative risk of a major decline in overall health was
      1.63 (95 percent confidence interval, 1.26 to 2.08) for continuously uninsured
      participants and 1.41 (95 percent confidence interval, 1.11 to 1.78) for
      intermittently uninsured participants, as compared with continuously insured
      participants. A new difficulty in walking or climbing stairs was also more likely
      to develop in the continuously or intermittently uninsured participants than in
      the continuously insured participants (28.8 percent, 26.4 percent, and 17.1
      percent of the three groups, respectively; P<0.001 for both comparisons). The
      adjusted relative risk of such a new physical difficulty was 1.23 (95 percent
      confidence interval, 1.02 to 1.47) for the continuously uninsured participants
      and 1.26 (95 percent confidence interval, 1.01 to 1.54) for the intermittently
      uninsured participants. CONCLUSIONS: The lack of health insurance is associated
      with an increased risk of a decline in overall health among adults 51 to 61 years
      old.

PMID- 11596592
TI  - Clinical practice. Extracranial carotid stenosis.

PMID- 11596593
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 31-2001. A 70-year-old woman with end-stage renal disease and
      cutaneous ulcers.

PMID- 11596594
TI  - Surgery for emphysema--not for everyone.

PMID- 11596595
TI  - Older age--not a barrier to cancer treatment.

PMID- 11596596
TI  - Evidence that human cardiac myocytes divide after myocardial infarction.

PMID- 11596597
TI  - Evidence that human cardiac myocytes divide after myocardial infarction.

PMID- 11596598
TI  - Evidence that human cardiac myocytes divide after myocardial infarction.

PMID- 11596599
TI  - Amyotrophic lateral sclerosis.

PMID- 11596600
TI  - Respiratory syncytial virus.

PMID- 11596601
TI  - Respiratory syncytial virus.

PMID- 11596602
TI  - Advances in mechanical ventilation.

PMID- 11596603
TI  - Traumatic cervical-spine disruption.

PMID- 11596604
TI  - Nongenetic male pseudohermaphroditism and reduced prenatal growth.

PMID- 11596605
TI  - Collective bargaining by physicians--labor law, antitrust law, and organized
      medicine.

PMID- 11596606
TI  - From the Centers for Disease Control and Prevention. Update: Fatal and severe
      liver injuries associated with Rifampin and Pyrazinamide for latent tuberculosis
      infection, and revisions in American Thoracic Society/CDC recommendations--United
      States, 2001.

PMID- 11596607
TI  - JAMA patient page. Type 2 diabetes mellitus in children.

PMID- 11596608
TI  - [The effectiveness paradox in complementary medicine].

PMID- 11596609
TI  - [All is possible--but only within the scope of scientific method].

PMID- 11596610
TI  - Studies in mistletoe therapy and cancer: still waiting for the the big step
      forward.

PMID- 11596611
TI  - Medical museums.

PMID- 11596612
TI  - Crotamiton and narrow-band UVB phototherapy: novel approaches to alleviate
      pruritus of breast carcinoma skin infiltration.

PMID- 11596613
TI  - Re: medical records vs. patient self-rating.

PMID- 11596614
TI  - Theoretical and clinical concerns about brain death: the debate continues.

PMID- 11596615
TI  - Beyond brain death?

PMID- 11596616
TI  - [Contraception].

PMID- 11596617
TI  - Effect of left atrial size and function on P-wave dispersion: a study in patients
      with paroxysmal atrial fibrillation.
AB  - BACKGROUND: Paroxysmal atrial fibrillation (PAF), a common arrhythmia, is caused
      by the fractionated and nonhomogeneous propagation of sinus impulse. HYPOTHESIS:
      This study was undertaken to examine the effect of left atrial (LA) dimension and
      function on P-wave dispersion (deltaP) in unselected patients with PAF and health
      controls. METHOD: In this study, 62 consecutive patients with PAF (32 men, 30
      women, mean age 55+/-11 years) and 62 age- and gender-matched healthy controls
      (33 men, 29 women, mean age 52+/-13 years) were studied to compare the effect of
      LA size, volume, and function on deltaP (difference between maximum and minimum P
      wave duration on 12-lead electrocardiogram). RESULTS: P-wave dispersion in
      patients with PAF and normal LA diastolic diameter (LAD) was longer than that in
      controls with normal LA size (53+/-8 vs. 34+/-8 ms, p < 0.001). P-wave dispersion
      increased in patients with PAF (62+/-12 vs. 53+/-8 ms, p = 0.003) and controls
      (40+/-7 vs. 34+/-8 ms, p = 0.005) with increased LAD. Presence or absence of PAF
      did not interact with LAD for their effect on deltaP (2 x 2 analysis of variance
      test p = 0.20). In the PAF group, deltaP correlated with LAD (r = 0.43, p =
      0.002), LA diastolic volume (r = 0.6, p < 0.001), and LA ejection fraction (AEF)
      (r = - 0.33, p = 0.05). The AEF was preserved when LAD increased in the patients
      without PAF (0.52+/-0.07 vs. 0.57+/-0.10, p = NS), however was significantly
      decreased in the PAF group (0.37+/-0.12 vs. 0.49+/-0.10, p = 0.01). On
      multivariate logistic regression analysis, only deltaP retained significance on
      development of PAF. CONCLUSION: It was concluded that deltaP increased in
      patients with PAF and normal LA size. In controls with increased LA size, deltaP
      increased but did not reach the levels attained in patients with PAF. The AEF was
      decreased in patients with PAF but was preserved in those without PAF. These
      findings can be explained by the changes in LA microarchitecture which
      concurrently decreased atrial myocardial contraction, increased deltaP, and
      predisposed to PAF.

PMID- 11596618
TI  - Who should receive hepatitis A vaccine?

PMID- 11596619
TI  - A 67-year-old woman with sudden onset of chest pain and dyspnea.

PMID- 11596621
TI  - Patient information. Living with fibromyalgia.

PMID- 11596620
TI  - Elusive syndromes: treating the biologic basis of fibromyalgia and related
      syndromes.
AB  - Newer theories suggest that patients with fibromyalgia have a biologic
      predisposition to perceiving pain with more sensitivity than people without
      fibromyalgia. Several biologic triggers are implicated as possibly initiating or
      worsening the symptoms of fibromyalgia. Treatments to manage pain, help with
      sleep, and, when needed, treat cognitive disturbances show some success.

PMID- 11596622
TI  - Information at hand: using handheld computers in medicine.
AB  - Call them handhelds, palm-tops, or personal digital assistants (PDAs), pocket
      sized computers are becoming a common feature on the medical landscape. As the
      technology improves, more programs become available, and the demands of medical
      practice heighten, physicians are recognizing the benefits of having information
      available at the point of care. This article reviews the use of handheld
      computers in medicine, emphasizing how they might help the practicing physician.

PMID- 11596623
TI  - Handheld computers in medicine: the future is not here yet.

PMID- 11596624
TI  - Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: diagnosis and
      treatment.
AB  - Prompt recognition of thrombotic thrombocytopenic purpura-hemolytic uremic
      syndrome (TTP-HUS) and initiation of plasma exchange treatment is critical as it
      substantially decreases mortality. Nevertheless, death and long-term
      complications remain common. The recent relaxation of diagnostic criteria has
      dramatically increased the number of patients treated for clinically suspected
      TTP-HUS.

PMID- 11596625
TI  - Meningococcal vaccination for college freshmen.

PMID- 11596626
TI  - Valvular heart disease update.

PMID- 11596627
TI  - Current medical management of valvular heart disease.
AB  - Drug therapy plays a key role in the management of valvular heart disease, though
      in many cases it does not alter its course or delay the need for surgery. The
      importance of drug therapy lies in stabilizing the patient's condition when the
      disease is due to abnormal valve structure, and in treating the underlying
      condition when the condition is due to a functional abnormality. Drug therapy
      also lowers the risk of bacterial endocarditis and rheumatic fever.

PMID- 11596628
TI  - A 65-year-old man with progressive shortness of breath.

PMID- 11596629
TI  - The effects of HGMFs on the plant gravisensing system.
AB  - High Gradient Magnetic Fields (HGMFs) offer new opportunities for studying the
      gravitropic system of plants. However, it is necessary to analyze the influence
      that HGMF can have on cellular processes and structures that may not be related
      to amyloplasts displacement. This paper considers possible HGMF effects on
      plants, which may accompany HGMF stimulation of amyloplasts and contribute to the
      mechanisms of the HGMF-induced curvature.

PMID- 11596630
TI  - Effects of slow clinorotation on lipid contents and proton permeability of
      thylakoid membranes of pea chloroplasts.
AB  - Photochemical characteristics and lipid composition of thylakoid membranes from
      12 day-old pea leaves that were exposed to slow clino-rotation were examined and
      compared with a vertical control. Proton permeability of thylakoid membranes was
      estimated from light-induced proton uptake (delta H+) and post-illumination
      proton efflux in chloroplast suspensions. The delta pH magnitude was calculated
      from the level of light-induced quenching of 9-aminoacridine fluorescence. Proton
      permeability of thylakoid membranes increased during exposure to clino-rotation.
      When subsequently transferred to darkness, proton efflux increased almost 2-fold
      in clinorotated leaves. The results were compared with data on pigment and polar
      lipid composition of photosynthetic membranes in clino-rotated and control
      plants. It was concluded that both the increase of proton permeability and the
      decrease of polar lipid content in chloroplasts were induced by clino-rotation.

PMID- 11596631
TI  - Gravitational force regulates elongation growth of Arabidopsis hypocotyls by
      modifying xyloglucan metabolism.
AB  - Growth of dark-grown Arabidopsis hypocotyls was suppressed under hypergravity
      conditions (300 g), or was stimulated under microgravity conditions in space
      (Space Shuttle STS-95). The mechanical extensibility of cell walls decreased and
      increased under hypergravity and microgravity conditions, respectively. The
      amounts of cell wall polysaccharides (pectin, hemicellulose-I, hemicellulose-II
      and cellulose) per unit length of hypocotyls increased under hypergravity
      conditions, and decreased under microgravity conditions. The amount and the
      molecular mass of xyloglucans also increased under the hypergravity conditions,
      while those decreased under microgravity conditions. The activity of xyloglucan
      degrading enzymes extracted from hypocotyl cell walls decreased and increased
      under hypergravity and microgravity conditions, respectively. These results
      indicate that the amount and the molecular mass of xyloglucans are affected by
      the magnitude of gravity and that such changes are caused by changes in
      xyloglucan-degrading activity. Modifications of xyloglucan metabolism as well as
      the thickness of cell walls by gravity stimulus may be the primary event
      determining the cell wall extensibility, thereby regulating the growth rate of
      Arabidopsis hypocotyls.

PMID- 11596632
TI  - Leaf senescence under various gravity conditions: relevance to the dynamics of
      plant hormones.
AB  - Effects of simulated microgravity and hypergravity on the senescence of oat leaf
      segments excised from the primary leaves of 8-d-old green seedlings were studied
      using a 3-dimensional (D) clinostat as a simulator of weightlessness and a
      centrifuge, respectively. During the incubation with water under 1-g conditions
      at 25 degrees C in the dark, the loss of chlorophyll of the segments was found
      dramatically immediately after leaf excision, and leaf color completely turned to
      yellow after 3-d to 4-d incubation. In this case kinetin (10 micromolar) was
      effective in retarding senescence. The application of simulated microgravity
      conditions on a 3-D clinostat enhanced chlorophyll loss in the presence or
      absence of kinetin. The loss of chlorophyll was also enhanced by hypergravity
      conditions (ca. 8 to 16 g), but the effect was smaller than that of simulated
      microgravity conditions on the clinostat. Jasmonates (JAs) and abscisic acid
      (ABA) promoted senescence under simulated microgravity conditions on the
      clinostat as well as under 1-g conditions. After 2-d incubation with water or 5-d
      incubation with kinetin, the endogenous levels of JAs and ABA of the segments
      kept under simulated microgravity conditions on the clinostat remained higher
      than those kept under 1-g conditions. These findings suggest that physiological
      processes of leaf senescence and the dynamics of endogenous plant hormone levels
      are substantially affected by gravity.

PMID- 11596633
TI  - Life sciences flight hardware development for the International Space Station.
AB  - During the construction phase of the International Space Station (ISS), early
      flight opportunities have been identified (including designated Utilization
      Flights, UF) on which early science experiments may be performed. The focus of
      NASA's and other agencies' biological studies on the early flight opportunities
      is cell and molecular biology; with UF-1 scheduled to fly in fall 2001, followed
      by flights 8A and UF-3. Specific hardware is being developed to verify design
      concepts, e.g., the Avian Development Facility for incubation of small eggs and
      the Biomass Production System for plant cultivation. Other hardware concepts will
      utilize those early research opportunities onboard the ISS, e.g., an Incubator
      for sample cultivation, the European Modular Cultivation System for research with
      small plant systems, an Insect Habitat for support of insect species. Following
      the first Utilization Flights, additional equipment will be transported to the
      ISS to expand research opportunities and capabilities, e.g., a Cell Culture Unit,
      the Advanced Animal Habitat for rodents, an Aquatic Facility to support small
      fish and aquatic specimens, a Plant Research Unit for plant cultivation, and a
      specialized Egg Incubator for developmental biology studies. Host systems (Figure
      1A, B: see text), e.g., a 2.5 m Centrifuge Rotor (g-levels from 0.01-g to 2-g)
      for direct comparisons between g and selectable g levels, the Life Sciences
      Glovebox for contained manipulations, and Habitat Holding Racks (Figure 1B: see
      text) will provide electrical power, communication links, and cooling to the
      habitats. Habitats will provide food, water, light, air and waste management as
      well as humidity and temperature control for a variety of research organisms.
      Operators on Earth and the crew on the ISS will be able to send commands to the
      laboratory equipment to monitor and control the environmental and experimental
      parameters inside specific habitats. Common laboratory equipment such as
      microscopes, cryo freezers, radiation dosimeters, and mass measurement devices
      are also currently in design stages by NASA and the ISS international partners.

PMID- 11596634
TI  - Gravisensing in single-celled systems: characean rhizoids and protonemata.
AB  - Gravitropically tip-growing cell types are attractive unicellular model systems
      for investigating the mechanisms and the regulation of gravitropism. Especially
      useful for studying the mechanisms of positive and negative gravitropic tip
      growth are characean rhizoids and protonemata. They originate from the same cell
      type, show the same overall cell shape, cytoplasmic zonation, arrangement of
      actin and microtubule cytoskeleton, use statoliths for gravisensing, but show
      opposite gravitropism. In both cell types, actin microfilaments are complexly
      organized in the apical dome,where a dense spherical actin array is colocalized
      with spectrin-like epitopes and a unique endoplasmic reticulum aggregate, the
      structural center of the Spitzenkorper. The opposite gravitropic responses seem
      to be based on differences in the actin-organized anchorage of the Spitzenkorper
      and the actin-mediated transport of statoliths. In negatively gravitropic (upward
      bending) protonemata, the statoliths-induced drastic upward shift of the cell tip
      is preceded by a relocalization of dihydropyridine-binding calcium channels and
      of the apical calcium gradient to the upper flank (bending by bulging). Such
      relocalizations have not been observed in positively gravitropically responding
      (downward growing) rhizoids in which statoliths sedimentation is followed by
      differential flank growth (bending by bowing). This paper reviews the current
      knowledge and hypotheses on the mechanisms of the opposite gravitropic responses
      in characean rhizoids and protonemata.

PMID- 11596635
TI  - Gravitropism in cut flower stalks of snapdragon.
AB  - The negative gravitropic response of cut flower stalks is a complex multistep
      process that requires the participation of various cellular components acting in
      succession or in parallel. The process was particularly characterized in
      snapdragon (Antirrhinum majus L.) spikes with regard to (1) gravity stimulus
      perception associated with amyloplast reorientation; (2) stimulus transduction
      mediated through differential changes in the level, action and related genes of
      auxin and ethylene and their possible interaction; (3) stimulus response
      associated with differential growth leading to stalk curvature; (4) involvement
      of cytosolic calcium and actin cytoskeleton. Results show that the gravity
      induced amyloplast reorientation, differential over-expression of two early auxin
      responsive genes and asymmetrical distribution of free IAA are early events in
      the bending process. These precede the asymmetrical ethylene production and
      differential stem growth, which was derived from initial shrinkage of the upper
      stem side and a subsequent elongation of the lower stem side. Results obtained
      with various calcium- and cytoskeleton-related agents indicate that cytosolic
      calcium and actin filaments may play essential roles in gravitropism-related
      processes of cut flower stalks. Therefore, modulators of these two physiological
      mediators may serve as means for controlling any undesired gravitropic bending.

PMID- 11596636
TI  - Automorphogenesis and gravitropism of plant seedlings grown under microgravity
      conditions.
AB  - Plant seedlings exhibit automorphogenesis on clinostats. The occurrence of
      automorphogenesis was confirmed under microgravity in Space Shuttle STS-95
      flight. Rice coleoptiles showed an inclination toward the caryopsis in the basal
      region and a spontaneous curvature in the same adaxial direction in the
      elongating region both on a three-dimensional (3-D) clinostat and in space. Both
      rice roots and Arabidopsis hypocotyls also showed a similar morphology in space
      and on the 3-D clinostat. In rice coleoptiles, the mechanisms inducing such an
      automorphic curvature were studied. The faster-expanding convex side of rice
      coleoptiles showed a higher extensibility of the cell wall than the opposite
      side. Also, in the convex side, the cell wall thickness was smaller, the turnover
      of the matrix polysaccharides was more active, and the microtubules oriented more
      transversely than the concave side, and these differences appear to be causes of
      the curvature. When rice coleoptiles grown on the 3-D clinostat were placed
      horizontally, the gravitropic curvature was delayed as compared with control
      coleoptiles. In clinostatted coleoptiles, the corresponding suppression of the
      amyloplast development was also observed. Similar results were obtained in
      Arabidopsis hypocotyls. Thus, the induction of automorphogenesis and a
      concomitant decrease in graviresponsiveness occurred in plant shoots grown under
      microgravity conditions.

PMID- 11596637
TI  - Effects of spaceflight (STS-87) on tropisms and plastid positioning in
      protonemata of the moss Ceratodon purpureus.
AB  - Apical cells of moss protonemata represent a single-celled system that perceives
      and reacts to light (positive and negative phototropism) and to gravity (negative
      gravitropism). Phototropism completely overrides gravitropism when apical cells
      are laterally irradiated with relatively high red light intensities, but below a
      defined light intensity threshold gravitropism competes with the phototropic
      reaction. A 16 day-long exposure to microgravity conditions demonstrated that
      gravitropism is allowed when protonemata are laterally illuminated with light
      intensities below 140 nmol m-2s-1. Protonemata that were grown in darkness in
      microgravity expressed an endogenous tendency to grow in arcs so that the overall
      culture morphology resembled a clockwise spiral. However this phenomenon only was
      observed in cultures that had reached a critical age and/or size. Organelle
      positioning in dark-grown apical cells was significantly altered in microgravity.
      Gravisensing most likely involves the sedimentation of starch-filled amyloplasts
      in a well-defined area of the tip cell. Amyloplasts that at 1-g are sedimented
      were clustered at the apical part of the sedimentation zone in microgravity.
      Clustering observed in microgravity or during clino-rotation significantly
      differs from sedimentation-induced plastid aggregations after inversion of tip
      cells at 1-g.

PMID- 11596638
TI  - An active role of the amyloplasts and nuclei of root statocytes in
      graviperception.
AB  - Three main phases are discerned in the gravitropic reaction: perception of a
      gravitational stimulus, its transduction, and fixation of the reaction resulting
      in bending of an organ. According to the starch-statolith hypothesis of Nemec and
      Haberlandt, amyloplasts in the structurally and functionally specialized
      graviperceptive cells (statocytes) sediment in the direction of a gravitational
      vector in the distal part of a cell while a nucleus is in the proximal one. If
      amyloplasts appear to act as gravity sensors, the receptors, which interact with
      sedimented amyloplasts, and next signaling are still unclear. An analysis of the
      structural-functional organization of cells in different root cap layers of such
      higher plants as pea, Arabidopsis thaliana, and Brassica rapa grown under 1 g, on
      the clinostats, and in microgravity, allows us to support the hypothesis that
      amyloplasts function as statoliths in statocytes, but they may not be only the
      passive statolithic mass. We propose that amyloplasts fulfill a more complex
      function by interacting with a receptor, which is a nucleus, in transduction of
      some signal to it. Gravity-induced statolith movement in certain order leads to a
      new functional connection between gravity susceptors--amyloplasts and a receptor-
      a nucleus receiving some signal presumedly of a mechanical or biochemical nature
      from the amyloplasts. During gravitropism, sugar signaling could induce
      expression of genes encoding auxin transport proteins in a nucleus giving the
      nucleus an intermediate role in signal trunsduction following perception.

PMID- 11596639
TI  - Sedimentable amyloplasts in starch sheath cells of woody stems of Japanese
      cherry.
AB  - We examined whether sedimentable amyloplasts act as statolith in the perception
      of gravity in woody stems using the elongated internodes of Japanese cherry
      (Prunus jamasakura Sieb. ex Koidz.). In the internode of the seedlings grown on
      earth, amyloplasts were found sedimented at the distal end of each cell of the
      endodermal starch sheath tissue. In the internode grown on three-dimensional (3
      D) clinostat, amyloplasts were dispersed throughout the cell matrix in the
      endodermal starch sheath tissue. After changing the positions of the internode
      from vertical to horizontal, re-sedimentation of amyloplasts toward the direction
      of gravity was completed in 1h, whereas the bending of the internode was observed
      after 12 days. We propose that sedimentable amyloplasts in the endodermal starch
      sheath cells may play a role in gravity perception leading to secondary xylem
      formation in the secondary thickening growth and eccentric growth in gravi
      bending of tree stems.

PMID- 11596640
TI  - Lithium-induced changes in gravicurvature, statocyte ultrastructure and calcium
      balance of pea roots.
AB  - Calcium signaling has been implicated in plant graviperception. In order to
      investigate the role of intracellular calcium in the process, I used lithium ions
      (LiCl), which suppress inositol 1,4,5-trisphosphate (IP3) cycling and signaling
      by inhibiting inositol-1-phosphatase. After 4 h of gravistimulation, no curvature
      was observed in 81% of the roots of 5-day Pisum sativum seedlings pretreated with
      5 mM LiCl. Structural features of statocyte ultrastructure in these roots were
      the following: loss of a cellular polarity, appearance of amyloplast clusters,
      condensed mitochondria, local dilations in a perinuclear space, increases in a
      relative volume of vacuoles. The intensity of a cytochemical reaction
      (pyroantimonate staining which detected Ca2+ ions) was moderate: the Ca2+
      pyroantimonate deposits were observed in all organelles. There were few granules
      of this precipitate in a hyaloplasm of the statocytes. Mitochondria and vacuoles
      were found to contain more granules of the precipitate compared with the
      controls. Additionally, Ca(2+)-ATPase activity in the statocytes of pea roots
      pretreated with LiCl was approximately the same as in control roots. Data
      obtained by using inhibitor of inositol signaling suggest that the observed
      effects of LiCl on root gravicurvature and ultrastructure of root statocytes were
      due to effects on Ca2+ homeostasis, particularly on IP3-mediated release of
      intracellular Ca2+ which can be inhibited by inositol depletion. The work
      demonstrates the key role played by second messengers (Ca2+ and IP3) in a gravity
      perception and response.

PMID- 11596641
TI  - Cytochemical localization of calcium in soybean root cap cells in microgravity.
AB  - The antimonate precipitation technique was used to evaluate the effects of
      microgravity and ethylene on the cellular and subcellular distribution of free
      calcium ions in soybean root apices. Soybean (Glycine max L. [Merr.]) dry seeds
      were launched, activated by hydration, and germinated in the presence of KMnO4
      (to remove ethylene) and in its absence onboard the space shuttle Columbia during
      the STS-87 mission. Primary root apices of 6-day old seedlings were fixed for
      electron microscopy after landing. Ultrastructural studies indicated that
      antimonate precipitation appeared as individual electron-dense particles which
      were more or less round in shape and varied in diameter from 10 nm (minimum size
      beginning from which the particles were well identified) to 90 nm. It was
      revealed that analyzed root cap cells varied in both the precipitate particle
      sizes and the amount particles per unit of the cellular area. In both flight and
      ground control treatments, antimonate precipitation level increases from apical
      meristem cells to peripheral (secretory) cells of root apices. In root cap
      statocytes, subcellular localization of precipitate particles was revealed in the
      cytoplasm, nucleus and small vacuoles. The quantitative analysis showed a
      reduction of precipitate density in the cytoplasm and the nucleus, and an
      increase in precipitate density in the vacuoles from statocytes of both
      spaceflight treatments in comparison with ground controls.

PMID- 11596642
TI  - Pea chloroplasts under clino-rotation: lipid peroxidation and superoxide
      dismutase activity.
AB  - The lipid peroxidation (LP) intensity and the activity of the antioxidant enzyme
      superoxide dismutase (SOD) were studied in chloroplasts of pea (Pisum sativum L.)
      plants grown for 7 and 14 days under clino-rotation. An increase in LP levels in
      chloroplasts during both terms of clinorotation in comparison with stationary
      controls was documented. SOD activity increased in chloroplasts of plants that
      were clino-rotated for seven days. SOD has a significant protective effect by
      diminishing the availability of O2-. However, under more prolonged clino-rotation
      (14 days), SOD activity decreased but was still higher than in the control
      samples. In accordance with Selye's oxidative stress theory (Selye, 1956;
      modified by Leshem et al., 1998), plants that were clino-rotated for seven days
      are presumed to be in a stage of resistance while 14-day plants reached a stage
      of exhaustion.

PMID- 11596643
TI  - The effects of extended clinorotation on potato minituber formation and
      structure.
AB  - Formation and structure of potato minitubers grown aseptically for 30 days on a
      horizontal clinostat and in stationary control have been studied by light and
      electron microscopy. It was demonstrated that the number of plants that formed
      minitubers, their size and fresh weight, was higher when clino-rotated than in
      the stationary control. It was revealed that the amount of amyloplasts in
      parenchyma cell sections was doubled in minitubers formed under clino-rotation.
      Other factors (shape of minitubers and size of reserve parenchyma cells) did not
      differ from the stationary control. The changes in amyloplast ultrastructure
      suggest accelerated cell maturity of potato reserve parenchyma in extended clino
      rotation.

PMID- 11596644
TI  - Physiological characterization of gravitaxis in Euglena gracilis and Astasia
      longa studied on sounding rocket flights.
AB  - Euglena gracilis is a photosynthetic, unicellular flagellate found in eutrophic
      freshwater habitats. The organisms control their vertical position in the water
      column using gravi- and phototaxis. Recent experiments demonstrated that negative
      gravitaxis cannot be explained by passive buoyancy but by an active physiological
      mechanism. During space experiments, the threshold of gravitaxis was determined
      to be between 0.08 and 0.12 x g. A strong correlation between the applied
      acceleration and the intracellular cAMP and Ca2+ was observed. The results
      support the hypothesis, that the cell body of Euglena, which is denser than the
      surrounding medium exerts a pressure onto the lower membrane and activates
      mechanosensitive Ca2+ channels. Changes in the membrane potential and the cAMP
      concentration are most likely subsequent elements in a signal transduction chain,
      which results in reorientation strokes of the flagellum.

PMID- 11596645
TI  - Gravity-dependent reactions of the moss Pohlia nutans protonemata.
AB  - In darkness, protonemata of Pohlia nutans (Hedw.) grew negatively gravitropically
      (upwards). However, not all filaments became gravitropic immediately after
      transfer to darkness. Some of them (~20%) for several days grew in different
      directions with respect to gravity. The apical cells of those protonemata
      predominantly contained multiple chloroplasts. The intensity of chlorophyll
      fluorescence rapidly decreased in the apical cells of such protonemata while
      starch content increased in comparison with upright growing protonemata. Light,
      especially in the red and blue part of the spectrum, inhibited protonemal
      gravitropism. Red light induced stronger inhibitory effects than blue light. Red
      light of 1.0 to 1.5 micromoles m-2 s-1 intensity induced bud differentiation in
      apical cells on almost all side branches of main protonemal filaments. Bright
      fluorescence of F-actin bundles in the tip of apical protonematal cells and a
      delicately fluorescing network enclosing plastids basal to the tip in a
      sedimentation zone were visualized. Bright fluorescence of actin as local patches
      and fine prominent axially oriented bundles was observed in cells of gametophore
      buds.

PMID- 11596646
TI  - Growth and development in higher plants under simulated microgravity conditions
      on a 3-dimensional clinostat.
AB  - Growth and development of etiolated pea (Pisum sativum L. cv. Alaska) and maize
      (Zea mays L. cv. Golden Cross Bantam) seedlings grown under simulated
      microgravity conditions were intensively studied using a 3-dimensional clinostat
      as a simulator of weightlessness. Epicotyls of etiolated pea seedlings grown on
      the clinostat were the most oriented toward the direction far from cotyledons.
      Mesocotyls of etiolated maize seedlings grew at random and coleoptiles curved
      slightly during clinostat rotation. Clinostat rotation promoted the emergence of
      the 3rd internodes in etiolated pea seedlings, while it significantly inhibited
      the growth of the 1st internodes. In maize seedlings, the growth of coleoptiles
      was little affected by clinostat rotation, but that of mesocotyls was suppressed,
      and therefore, the emergence of the leaf out of coleoptile was promoted.
      Clinostat rotation reduced the osmotic concentration in the 1st internodes of pea
      seedlings, although it has little effect on the 2nd and the 3rd internodes.
      Clinostat rotation also reduced the osmotic concentrations in both coleoptiles
      and mesocotyls of maize seedlings. Cell-wall extensibilities of the 1st and the
      3rd internodes of pea seedlings grown on the clinostat were significantly lower
      and higher as compared with those on 1 g conditions, respectively. Cell-wall
      extensibility of mesocotyls in seedlings grown on the clinostat also decreased.
      Changes in cell wall properties seem to be well correlated to the growth of each
      organ in pea and maize seedlings. These results suggest that the growth and
      development of plants is controlled under gravity on earth, and that the growth
      responses of higher plants to microgravity conditions are regulated by both cell
      wall mechanical properties and osmotic properties of stem cells.

PMID- 11596647
TI  - Effects of dietary cholesterol restriction in a feline model of Niemann-Pick type
      C disease.
AB  - A feline model of Niemann-Pick disease type C (NPC) was employed to evaluate the
      effect of dietary cholesterol restriction on progression of disease. Two NPC
      affected treated cats were fed a cholesterol-restricted diet beginning at 8 weeks
      of age; the cats remained on the diet for 150 and 270 days respectively. The
      study goal was to lower the amount of low density lipoprotein (LDL) available to
      cells, hypothetically reducing subsequent lysosomal accumulation of unesterified
      cholesterol and other lipids. Neurological progression of disease was not altered
      and dietary cholesterol restriction did not significantly decrease storage in NPC
      affected treated cats. One NPC-affected treated cat had decreased serum alkaline
      phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver
      lipid concentrations of unesterified cholesterol, cholesterol ester and
      phospholipids in NPC-affected treated cats were similar to those seen in NPC
      affected untreated cats. Ganglioside concentrations in the NPC-affected treated
      cats and NPC-affected untreated cats were similar. Histological findings in liver
      sections from NPC-affected treated cats showed a diffuse uniform microvacuolar
      pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous
      macro/microvacuolar pattern and prominent nodular fibrosis in NPC-affected
      untreated cats. Similar differences in vacuolar patterns were seen in splenic
      macrophages. Although some hepatic parameters were modified, dietary cholesterol
      restriction did not appear to alter disease progression in NPC-affected kittens.

PMID- 11596648
TI  - The intellectual abilities of early-treated individuals with pyridoxine
      nonresponsive homocystinuria due to cystathionine beta-synthase deficiency.
AB  - The pathological sequelae of untreated homocystinuria due to cystathionine beta
      synthase deficiency include ectopia lentis, osteoporosis, thromboembolic events
      and mental retardation. They occur at a significantly higher rate with poorer
      mental capabilities (mean IQ = 57) in the untreated pyridoxine-nonresponsive
      individuals. The mental capabilities of 23 pyridoxine-nonresponsive individuals
      with 339 patient-years of treatment were assessed using age-appropriate
      psychometric tests and were compared to those of 10 unaffected siblings
      (controls). Of the 23 individuals, 19 were diagnosed through newborn screening
      with early treatment, two were late-detected and two were untreated at the time
      of assessment. Thirteen of the newborn, screened group who were compliant with
      treatment had no complications, while the remaining 6, who had poor compliance,
      developed complications. Good compliance was defined by a lifetime plasma free
      homocystine median < 11 micromol/L. The newborn screened, good compliance group
      (n = 13) with a mean age of 14.4 years (range 4.4-24.9) had mean full-scale IQ
      (FIQ) of 105.8 (range 84-120), while the poorly compliant group (n = 6) with a
      mean age of 19.9 years (range 13.8-25.5) had a mean FIQ of 80.8 (range 40-103).
      The control group (n = 10) with mean age of 19.4 years (range 9.7-32.9) years had
      a mean FIQ of 102 (range 76-116). The two late-detected patients aged 18.9 and
      18.8 years had FIQ of 80 and 102, while the two untreated patients aged 22.4 and
      11.7 years had FIQ of 52 and 53, respectively. There was no statistical evidence
      of significant differences between the compliant, early-treated individuals and
      their unaffected siblings (controls) except for the FIQ, which was significantly
      higher than that of the unaffected siblings (p = 0.0397). These data, despite the
      relatively small numbers, suggest that early treatment with good biochemical
      control (lifetime plasma free homocystine median < 11 micromol/L) seems to
      prevent mental retardation.

PMID- 11596650
TI  - Oxidation of galactose by galactose-1-phosphate uridyltransferase-deficient
      lymphoblasts.
AB  - The ability of EB virus-transformed lymphoblasts with undetectable galactose-1
      phosphate uridyltransferase (GALT) from 15 galactosaemic patients to oxidize [1
      (14)C]galactose to 14CO2 was compared to that of cells from 7 normal subjects.
      The oxidation of galactose but not of glucose was markedly diminished by cells
      from Q188R homozygous galactosaemic patients but was not absent. After 2.5 h
      these cells liberated 14CO2 at nearly 3% and at 5 h up to 9% of normal. Cells
      from patients homozygous for the S135L mutation produced much larger amounts of
      14CO2 (15-17% of normal) and were distinguishable from the Q188R homozygous
      cells. A cell line with a homozygous deletion of the GALT gene oxidized galactose
      at 7% of the normal rate, suggesting that pathways(s) other than GALT exist in
      these cells as well as Q188R homozygous cells for oxidation of galactose to CO2.
      Concentration dependence studies are consistent with the presence of a pathway
      that is unsaturable or has a very high Km The ability of 10(7) lymphoblasts with
      the S135L genotype to oxidize more than 7% of the sugar to 14CO2 in 5 h suggests
      the presence of residual GALT despite the inability to detect the activity by
      enzymatic analysis.

PMID- 11596649
TI  - Glycine N-methyltransferase deficiency: a novel inborn error causing persistent
      isolated hypermethioninaemia.
AB  - This paper reports clinical and metabolic studies of two Italian siblings with a
      novel form of persistent isolated hypermethioninaemia, i.e. abnormally elevated
      plasma methionine that lasted beyond the first months of life and is not due to
      cystathionine beta-synthase deficiency, tyrosinaemia I or liver disease. Abnormal
      elevations of their plasma S-adenosylmethionine (AdoMet) concentrations proved
      they do not have deficient activity of methionine adenosyltransferase I/III. A
      variety of studies provided evidence that the elevations of methionine and AdoMet
      are not caused by defects in the methionine transamination pathway, deficient
      activity of methionine adenosyltransferase II, a mutation in
      methylenetetrahydrofolate reductase rendering this activity resistant to
      inhibition by AdoMet, or deficient activity of guanidinoacetate
      methyltransferase. Plasma sarcosine (N-methylglycine) is elevated, together with
      elevated plasma AdoMet in normal subjects following oral methionine loads and in
      association with increased plasma levels of both methionine and AdoMet in
      cystathionine beta-synthase-deficient individuals. However, plasma sarcosine is
      not elevated in these siblings. The latter result provides evidence they are
      deficient in activity of glycine N-methyltransferase (GNMT). The only clinical
      abnormalities in these siblings are mild hepatomegaly and chronic elevation of
      serum transaminases not attributable to conventional causes of liver disease. A
      possible causative connection between GNMT deficiency and these hepatitis-like
      manifestations is discussed. Further studies are required to evaluate whether
      dietary methionine restriction will be useful in this situation.

PMID- 11596651
TI  - Congenital disorders of glycosylation type Ia and IIa are associated with
      different primary haemostatic complications.
AB  - Congenital disorders of glycosylation (CDG) type I are mostly due to a deficient
      phosphomannomutase activity, called CDG Ia. CDG IIa (mutations in the MGAT2 gene)
      results from a deficient activity of the Golgi enzyme N
      acetylglucosaminyltransferase II. CDG Ia patients predominantly have a thrombotic
      tendency, whereas our CDG IIa patient has an increased bleeding tendency, despite
      similar coagulation factor abnormalities in both types. We have investigated
      whether abnormally glycosylated platelet membrane glycoproteins are involved in
      the haemostatic complications of both CDG groups. In flow cytometry, the binding
      of Ricinus communis lectin (reactive with beta-galactose primarily) to control
      platelets increased after neuraminidase treatment: this increase was smaller (p <
      0.01) in CDG Ia patients (3.1 +/- 0.08 times) than in control platelets (8.5 +/-
      1.8 times) and did not occur in the CDG IIa patient. Platelet-rich plasma from
      CDG Ia patients, but not a CDG IIa patient. aggregated spontaneously and gel
      filtered platelets from CDG Ia patients agglutinated at very low concentrations
      of ristocetin, independently of von Willebrand factor (vWF). Accordingly, in
      stirred whole blood, the rate of single platelet disappearance of CDG Ia patients
      was twice that of control platelets. In contrast, perfusion of whole
      anticoagulated blood of the CDG IIa patient over collagen yielded markedly
      decreased platelet adherence to collagen at shear rates involving glycoprotein
      (GP) Ib-vWF interactions. Thus, abnormal glycosylation of platelet glycoproteins
      in CDG Ia enhances nonspecific platelet interactions, in agreement with a
      thrombotic tendency. The reduced GP Ib-mediated platelet reactivity with vessel
      wall components in the CDG IIa patient under flow conditions provides a basis for
      his bleeding tendency.

PMID- 11596652
TI  - Polyunsaturated fatty acid deficiency during dietary treatment of very long-chain
      acyl-CoA dehydrogenase deficiency. Rescue with soybean oil.
AB  - Nutritional management of very long-chain acyl-CoA dehydrogenase (VLCAD)
      deficiency is based on the avoidance of fasting and substitution of medium-chain
      triglycerides for long- and very long-chain triglycerides. We report two cases of
      this disease, which developed omega-6 essential fatty acid deficiency after three
      and five months from the beginning of nutritional therapy (SHS product: Monogen).
      This alteration could be especially dangerous in these patients owing to their
      possible susceptibility to the development of pigmentary retinopathy. The
      incorporation of linoleic acid as 3-4% of total caloric intake supported as
      soybean oil ameliorates this deficiency. We wish to remark on this early
      complication in the nutritional management of VLCAD deficiency and the
      possibility of rescue by the incorporation of soybean oil into the diet.

PMID- 11596653
TI  - Early-onset lysosomal glycogen storage disease with normal acid maltase.

PMID- 11596654
TI  - Partial effect of bromocriptine on lactose and galactose synthesis in a pregnant
      woman heterozygous for galactosaemia.
AB  - Bromocriptine combined with galactose restriction in the matenal diet seems to be
      partially effective in decreasing endogenous lactose and galactose synthesis,
      monitored in a pregnant woman heterozygous for galactosaemia at risk of producing
      a homozygous infant.

PMID- 11596655
TI  - A Korean girl with alpha-aminoadipic and alpha-ketoadipic aciduria accompanied
      with elevation of 2-hydroxyglutarate and glutarate.

PMID- 11596656
TI  - CblC/D defect combined with haemodynamically highly relevant VSD.
AB  - An infant with combined methylmalonic aciduria and homocystinuria (cblC/D defect)
      presented with significant VSD. She underwent successful cardiac surgery at 53
      days.

PMID- 11596658
TI  - PKU adults and their return to diet: predicting diet continuation and
      maintenance.

PMID- 11596657
TI  - Pitfalls in the detection of heterozygosity by allopurinol in a variant form of
      ornithine carbamoyltransferase deficiency.

PMID- 11596659
TI  - A common 2 bp deletion mutation in the glucose-6-phosphatase gene in Indian
      patients with glycogen storage disease type Ia.
AB  - This study reports a novel mutation which may be prevalent in Indian patients
      with glycogen storage disease type Ia.

PMID- 11596660
TI  - Factors controlling pancreatic cell differentiation and function.
AB  - Diabetes affects 4 to 5% of the population worldwide and is the most common
      metabolic disorder. The number of individuals diagnosed with diabetes is rapidly
      increasing, especially in the developed countries and the disorder frequently
      leads to secondary complications such as retinopathy, nephropathy, neuropathy and
      cardiovascular disease. Type II (non-insulin-dependent) diabetes mellitus is the
      most common form of diabetes, more than 90% of diagnosed cases, and results from
      insulin resistance, pancreatic beta-cell dysfunction, or a combination of both.
      The beta-cell dysfunction seems to result in part from an inability of the beta
      cells to produce and secrete sufficient amounts of active insulin in response to
      an increased demand for insulin. Type I (insulin-dependent) diabetes mellitus is
      caused by an autoimmune destruction of the insulin producing beta cells,
      resulting in insulin deficiency. The existing therapies for both types of
      diabetes are unsatisfactory since they do not offer a cure and are mostly not
      sufficient for preventing the secondary complications associated with diabetes.
      Thus, there is a great need for new improved therapies. This search is, however,
      hampered by our currently limited knowledge of the basic processes that control
      the proliferation, differentiation, survival and physiology of the beta cell.
      Over the last 7 to 8 years our knowledge concerning the development of the
      pancreas has increased substantially due to the use of genetically modified mice.
      Nevertheless, key questions regarding the control of proliferation and
      differentiation of pancreatic progenitor cells into fully functional beta cells
      remain to be solved.

PMID- 11596661
TI  - Diabetes mellitus and the stomach.
AB  - Many patients with diabetes mellitus complain of early satiety and postprandial
      gastric fullness. In 1945, these symptoms were first found to result from a
      gastric motor dysfunction which makes the delivery of ingesta into the small
      intestine, the time of their absorption and the related blood-glucose rise
      unpredictable. Consequently, insulin or hypoglycaemic agents are administered at
      inappropriate time points and poor glycaemic control ensues. About 50% of
      patients with Type I (insulin-dependent) and Type II (non-insulin-dependent)
      diabetes mellitus are affected. Hyperglycaemia may play an important role in the
      disorder: gastric emptying was found to be slower in states of induced
      hyperglycaemia than in euglycaemia. However, significantly reduced blood-glucose
      concentrations after therapy readjustment were not associated with an increase in
      emptying rate. Prolonged hyperglycaemia could alter nerve metabolism and
      contribute to the development of neuropathy. Severity of cardiovascular autonomic
      neuropathy, but not actual blood-glucose and glycated haemoglobin level, has been
      found to correlate with the degree of emptying impairment. Drugs enhancing
      gastric emptying could improve the coordination between insulin administration
      and the onset of nutrient absorption and thus glycaemic control. Disappointingly,
      trials to study the long-term effects of such drugs are scarce and their results
      predominantly negative. In conclusion, many diabetic patients have impaired
      gastric motor function which could contribute to poor glycaemic control. Evidence
      suggests that autonomic neuropathy is the main underlying factor. This review
      aims to offer a critical survey of all the data available at present on these
      topics.

PMID- 11596662
TI  - High prevalence of diabetes and impaired glucose tolerance in India: National
      Urban Diabetes Survey.
AB  - AIMS/HYPOTHESIS: There has been no reported national survey of diabetes in India
      in the last three decades, although several regional studies show a rising
      prevalence of diabetes. The aim of this study was to assess the prevalence of
      diabetes and impaired glucose tolerance in six major cities, covering all the
      regions of the country. METHODS: Using a stratified random sampling method, 11216
      subjects (5288 men; 5928 women) aged 20 years or above, representative of all
      socio-economic strata, were tested by OGTT. Demographic, anthropometric,
      educational and social details were recorded using a standard proforma. Physical
      activity was categorised using a scoring system. Body mass index (BMI) and waist
      to-hip ratio (WHR) were calculated. Glucose tolerance was classified using the 2
      h values (WHO criteria). Prevalence estimations were made taking into account the
      stratified sampling procedure. Group comparisons were done by t-test or analysis
      of variance or Z-test as relevant. Univariate and multiple logistic regression
      analyses were used to study the association of variables with diabetes and
      impaired glucose tolerance. RESULTS: Age standardised prevalences of diabetes and
      impaired glucose tolerance were 12.1% and 14.0% respectively, with no gender
      difference. Diabetes and impaired glucose tolerance showed increasing trend with
      age. Subjects under 40 years of age had a higher prevalence of impaired glucose
      tolerance than diabetes (12.8% vs 4.6%, p < 0.0001). Diabetes showed a positive
      and independent association with age, BMI, WHR, family history of diabetes,
      monthly income and sedentary physical activity. Age, BMI and family history of
      diabetes showed associations with impaired glucose tolerance.
      CONCLUSIONS/INTERPRETATION: This national study shows that the prevalence of
      diabetes is high in urban India. There is a large pool of subjects with impaired
      glucose tolerance at a high risk of conversion to diabetes.

PMID- 11596663
TI  - Antioxidants attenuate early up regulation of retinal vascular endothelial growth
      factor in streptozotocin-diabetic rats.
AB  - AIMS/HYPOTHESIS: A strong positive correlation has been found between lipid
      peroxidation product and vascular endothelial growth factor concentrations in the
      vitreous of patients with proliferative diabetic retinopathy. To establish a
      causal relation between diabetes-associated enhanced oxidative stress and
      vascular endothelial growth factor production, we evaluated two antioxidants, DL
      alpha-lipoic acid and taurine, on retinal vascular endothelial growth factor
      protein and mRNA expression and on parameters of oxidative stress in
      streptozotocin-diabetic rats. METHODS: Our experiments were on control rats and
      streptozotocin-diabetic rats with a 6-week duration of diabetes, treated with or
      without DL-alpha-lipoic acid (100 mg x kg(-1) x d(-1), i.p.) or taurine (1% in
      the diet) starting from induction of diabetes. Vascular endothelial growth factor
      protein in retinal homogenates was assessed by sandwich ELISA with an affinity
      purified polyclonal antibody and vascular endothelial growth factor mRNA by
      ribonuclease protection assay. Retinal lipid peroxidation products i.e.
      malondialdehyde plus 4-hydroxyalkenals were quantified with N-methyl-2
      phenylindole. Retinal reduced and oxidized glutathione, ascorbate,
      dehydroascorbate, and sorbitol pathway intermediates were measured
      spectrofluorometrically, and taurine by reverse-phase HPLC. RESULTS: Vascular
      endothelial growth factor protein concentration (means +/- SD) was increased in
      diabetic rats compared with control rats (33+/-7 vs 19+/-5 pg/mg total protein, p
      < 0.01) This increase was attenuated by taurine (26+/-8, p < 0.05) and prevented
      by DL-alpha-lipoic acid (21+/-4, p < 0.01). Vascular endothelial growth factor
      mRNA abundance was reduced by 1.4-fold in diabetic rats compared with control
      rats and this decrease was attenuated but not completely prevented by both
      antioxidants. Malondialdehyde plus 4-hydroxyalkenal concentration was increased
      in diabetic rats compared with control rats, and both antioxidants arrested
      accumulation of lipid peroxidation products. Taurine, reduced glutathione,
      oxidized glutathione, ascorbate, dehydroascorbate and sorbitol pathway
      intermediate concentrations as well as oxidized glutathione/reduced glutathione
      and dehydroascorbate/ascorbate ratios were similar in control and diabetic rats
      treated with or without taurine. CONCLUSION/INTERPRETATION: Oxidative stress is
      directly involved in up regulation of vascular endothelial growth factor protein
      in the retina during early diabetes.

PMID- 11596664
TI  - Influence of obesity and insulin sensitivity on phospholipid transfer protein
      activity.
AB  - AIMS/HYPOTHESIS: Phospholipid transfer protein plays a key role in lipoprotein
      metabolism by catalysing the transfer of phospholipids from triglyceride-rich
      lipoproteins to high-density lipoproteins and, also, within the high-density
      lipoprotein family, from particle to particle. This transfer results in a change
      of HDL particle size and the generation of pre-beta-high-density lipoproteins
      which function as initial lipid acceptors in the process of reverse cholesterol
      transport. Because adipose tissue is a source of phospholipid transfer protein we
      investigated the influence of obesity and insulin sensitivity on phospholipid
      transfer protein activity. METHODS: Using an exogenous substrate assay
      phospholipid transfer protein activity was measured in plasma specimens of 190
      normolipidaemic, non-diabetic subjects with BMI ranging from 19 to 43 kg/m2.
      Insulin sensitivity was measured by the short insulin tolerance test. RESULTS:
      Phospholipid transfer protein activity was associated with BMI (r = 0.46, p <
      0.01), body fat mass (r = 0.39, p < 0.01), subcutaneous fat area (r = 0.32, p <
      0.01) and plasma leptin concentration (r = 0.24, p < 0.01) but not with insulin
      sensitivity expressed as the k(s) of the insulin tolerance test (kITT value) (r =
      -0.14, p = 0.40). Accordingly, phospholipid transfer protein activity was higher
      in obese than in nonobese subjects. As determined by linear regression analysis,
      BMI was the sole predictor of phospholipid transfer protein activity in plasma
      explaining 22.2% of the activity (p< 0.01). CONCLUSIONS/INTERPRETATIONS: This
      data suggests that increased phospholipid transfer protein activity in obese
      subjects is a consequence of obesity itself without the contribution of insulin
      resistance and can be explained by increased synthesis of phospholipid transfer
      protein from the enlarged mass of adipose tissue.

PMID- 11596665
TI  - Study rationale and design of ADVANCE: action in diabetes and vascular disease-
      preterax and diamicron MR controlled evaluation.
AB  - AIMS/HYPOTHESIS: Patients with Type II (non-insulin-dependent) diabetes mellitus
      are at increased risk of macrovascular and microvascular disease, both of which
      are reduced by controlling raised blood pressure in hypertensive patients.
      Intensive glycaemic control has also been shown to reduce microvascular disease
      but the effects on macrovascular disease remain uncertain. This study will
      examine the hypotheses that lowering blood pressure with an ACE inhibitor
      diuretic combination and intensively controlling gylcaemia with a sulphonylurea
      based regimen in high-risk patients with Type II diabetes (both hypertensive and
      non-hypertensive) reduces the incidence of macrovascular and microvascular
      disease. METHODS: The study is a 2 x 2 factorial randomised controlled trial that
      will include 10000 adults with Type II diabetes at high risk of vascular disease.
      Following 6 weeks on open label perindopril-indapamide combination, eligible
      patients are randomised to continued perindopril-indapamide or matching placebo,
      and to an intensive gliclazide MR-based glucose control regimen or usual
      guidelines-based therapy. Primary outcomes are, first, the composite of nonfatal
      stroke, non-fatal myocardial infarction or cardiovascular death and, second, the
      composite of new or worsening nephropathy or diabetic eye disease. The scheduled
      average duration of treatment and follow-up is 4.5 years. The study will be
      conducted in approximately 200 centres in Australasia, Asia, Europe and North
      America. CONCLUSION/INTERPRETATION: ADVANCE is designed to provide reliable
      evidence on the balance of benefits and risks conferred by blood pressure
      lowering therapy and intensive glucose control therapy in high-risk diabetic
      patients, regardless of initial blood pressure or glucose concentrations.

PMID- 11596666
TI  - Stimulation in vivo of expression of intra-abdominal adipose tissue plasminogen
      activator inhibitor Type I by proinsulin.
AB  - AIMS/HYPOTHESIS: Impaired fibrinolytic system capacity secondary to increased
      plasminogen activator inhibitor type-1 expression has been suggested as a
      pathogenetic link between insulin resistance and increased cardiovascular risk in
      patients with Type II (non-insulin-dependent) diabetes mellitus, obesity, or
      both. In patients with syndromes of insulin resistance including those with Type
      II diabetes, precursors of insulin such as proinsulin can constitute more than
      50% of insulin-like molecules in blood. The aim of this study was to determine
      whether proinsulin can increase plasminogen activator inhibitor type-1 expression
      in intra-abdominal adipose tissue in vivo, potentially contributing to the
      increased PAI-1 seen with insulin resistance. METHODS: Lightly sedated normal
      rabbits were given intravenous proinsulin, insulin, or vehicle alone under
      euglycaemic clamp conditions with serial sampling of blood and assessment of PAI
      1 expression in visceral fat. RESULTS: Both proinsulin and insulin increased
      expression of plasminogen activator inhibitor type-1 in intra-abdominal adipose
      tissue, 5.3-fold (p = 0.006 vs control) and 2.5-fold (p = 0.031 vs control)
      respectively. PAI-1 inhibitor activity in blood peaked 3 h after administration
      of each, 5.1-fold, p = 0.020, and 3.4-fold, p = 0.004, respectively but did not
      change under control conditions. CONCLUSION/INTERPRETATION: Hyperproinsulinaemia
      can contribute to increased expression of plasminogen activator inhibitor type-1
      in intra-abdominal adipose tissue implicated in increasing PAI-1 activity in
      blood, impaired fibrinolysis, and accelerated atherogenesis typical of Type II
      diabetes.

PMID- 11596667
TI  - Insulin inhibits leptin receptor signalling in HEK293 cells at the level of janus
      kinase-2: a potential mechanism for hyperinsulinaemia-associated leptin
      resistance.
AB  - AIMS/HYPOTHESIS: Leptin resistance in obese humans seems to be predominantly
      caused by signalling abnormalities at the post receptor level. Leptin resistance
      in obese individuals is frequently associated with insulin resistance and
      pronounced hyperinsulinaemia indicating a negative crosstalk of the insulin and
      leptin signalling chain. METHODS: This hypothesis was tested using a cell model
      of peripheral leptin signalling, i. e. insulin-secreting cell lines (RINr1046
      38). Mechanisms for a crosstalk between the insulin and leptin signalling pathway
      were also studied in rat-1 and HEK293 cells overexpressing elements of the
      insulin and leptin signalling chain. RESULTS: The effects of leptin on insulin
      secretion are completely cancelled by a 4-h preincubation with 1 nmol/l insulin,
      supporting the hypothesis of a negative crosstalk of insulin and leptin
      signalling. We investigated the potential molecular mechanisms in more detail in
      HEK293 cells and Rat-1 fibroblasts that overexpressed proteins of the insulin and
      leptin signalling chain. Leptin (60 ng/ml) stimulated autophosphorylation of JAK
      2 in HEK 293 cells. This leptin effect could be inhibited by simultaneous
      treatment of cells with insulin. Furthermore, overexpression of the insulin
      receptor in HEK 293 cells clearly reduced JAK-2 phosphorylation and led further
      downstream to a diminished phosphatidylinositol 3-kinase activity. The inhibitory
      effect of the insulin signal could be partially prevented by transfection of the
      cells with an inactive mutant of the tyrosine phosphatase SHP-1.
      CONCLUSION/INTERPRETATION: In summary, our data suggest that the insulin receptor
      signalling pathway interferes with leptin signalling at the level of JAK-2.
      Inhibition of JAK-2 phosphorylation might occur through SHP-1-dependent pathways,
      indicating that hyperinsulinaemia contributes to the pathogenesis of leptin
      resistance.

PMID- 11596668
TI  - Placental glucose transport and utilisation is altered at term in insulin
      treated, gestational-diabetic patients.
AB  - AIMS/HYPOTHESIS: We have previously shown that placentae from patients with
      gestational diabetes mellitus who did not receive insulin had lower glucose
      transport and utilisation than non-diabetic control subjects. To assess the
      placental glucose handling characteristics of women with gestational diabetes
      mellitus receiving insulin, we examined glucose transport and utilisation in
      placentae from three groups of women after term delivery: those with gestational
      diabetes mellitus and receiving insulin (n = 9, insulin group); those with
      gestational diabetes mellitus and not receiving insulin (n = 10, no insulin
      group); and those with normal, non-diabetic pregnancies (n = 9, control group).
      METHODS: Dual perfusion of an isolated placental lobule was done using maternal
      glucose concentrations of 4, 8, 16 and 24 mmol/l. Glucose and L-lactate
      concentrations in the maternal and fetal effluents were measured. Direct glucose
      transfer from the maternal to the fetal effluent was measured using 14C-D
      glucose. Mean rates in micromol ming(-1) (wet tissue) at maternal glucose
      concentration of 8 mmol/l are shown. RESULTS: Glucose uptake from the maternal
      perfusate (insulin group 0.57, no insulin group 0.30) and net glucose transfer to
      the fetal effluent (insulin group 0.41, no insulin group 0.20) both increased in
      the placentae of women receiving insulin compared with the diabetic group not
      receiving insulin. Both groups of patients had lower placental glucose
      utilisation than the control group (insulin group 0.16, no insulin group 0.10,
      control group 0.25). CONCLUSION/INTERPRETATION: These results suggest that
      materno-fetal glucose transport increases in the placentae of women with
      gestational diabetes mellitus who receive insulin compared with those women who
      do not receive insulin.

PMID- 11596669
TI  - Cows' milk proteins cause similar Th1- and Th2-like immune response in diabetic
      and healthy children.
AB  - AIMS/HYPOTHESIS: Cows' milk proteins have been proposed to play a part in the
      pathogenesis of Type I (insulin-dependent) diabetes mellitus but both
      epidemiological and immunological studies have given conflicting results. Thus we
      aimed to study the immunological response to cows' milk proteins among diabetic
      and healthy children, focusing on the balance of Th1- and Th2-like lymphocytes.
      METHODS: Peripheral blood mononuclear cells from 30 Type I diabetic children (4
      to 18 years old) were examined and compared with peripheral blood mononuclear
      cells from 18 healthy age-matched control children (7 to 15 years old).
      Expression of IFN-gamma and IL-4 mRNA were detected by realtime RT-PCR and as
      protein by ELISA after stimulation with BSA, the ABBOS-peptide (a. a. 152-169)
      and beta-lactoglobulin (betaLG) from cows' milk and ovalbumin from hens' egg.
      Phytohaemagglutinin and keyhole limpet haemocyanin were used as positive and
      negative controls, respectively. RESULTS: Bovine serum albumin caused a weak Th2
      like response in Type I diabetic children, whereas BSA antibodies decreased with
      age only among healthy children. Otherwise, cows' milk proteins (BSA, ABBOS and
      betaLG) caused increased expression for IFN-gamma and IL-4 mRNA in diabetic and
      healthy children. BetaLG caused the strongest immunological response, which
      decreased with age only among diabetic children. However, ovalbumin from egg
      caused a similar activation of the immune system and the immune response was
      similar in both diabetic and healthy children. CONCLUSION/INTERPRETATION:
      Proteins from cows' milk caused an equal Th1- and Th2-like immune response in
      diabetic and healthy children. Thus, our results do not support the hypothesis
      that cows' milk antigens are important for the immune process associated with
      Type I diabetes.

PMID- 11596670
TI  - The metabolic syndrome influences the risk of chronic complications in patients
      with type II diabetes.
AB  - AIMS/HYPOTHESIS: We examined features of the metabolic syndrome to see if they
      modified the risk of chronic diabetic complications in patients with Type II (non
      insulin-dependent) diabetes mellitus. METHODS: A total of 85 randomly selected
      patients with the metabolic syndrome (WHO definition) were compared with 85 Type
      II diabetic patients matched for age, sex, duration of diabetes, glycaemic
      control and without the syndrome to assess the microvascular and macrovascular
      complications. RESULTS: The patients with the metabolic syndrome had a higher
      prevalence of cardiovascular disease (52 vs 21%, p < 0.001), microalbuminuria or
      macroalbuminuria (23 vs 7%, p = 0.003) and distal neuropathy (16 vs 6%, p =
      0.048) than patients without the syndrome. The patients with the metabolic
      syndrome had smaller LDL particle size (25.4+/-1.4 vs 26.4+/-1.1 nm; p < 0.001),
      which correlated with the ratio of serum triglycerides to HDL cholesterol (r = 
      0.64, p < 0.001). In a multiple logistic regression analysis the metabolic
      syndrome was associated with coronary heart disease (RR 3.84, p < 0.001) and
      microalbuminuria (RR 3.99, p = 0.01). Small LDL particle size was independently
      associated with neuropathy (RR 0.58; p = 0.04), whereas a high HbA1c was related
      to neuropathy (RR 1.69, p = 0.04), retinopathy (RR 1.53, p = 0.002) and
      microalbuminuria (RR 1.54, p = 0.01). CONCLUSION/INTERPRETATION: Although chronic
      hyperglycaemia is the main predictor of microvascular complications in patients
      with Type II diabetes, this risk is modified by some of the components of the
      metabolic syndrome.

PMID- 11596671
TI  - Erectile and endothelial dysfunction in Type II diabetes: a possible link.
AB  - AIMS/HYPOTHESIS: The aim of this study was to evaluate the relation between
      erectile dysfunction and endothelial functions, coagulation activation,
      peripheral and autonomic neuropathy in men with Type II (non-insulin-dependent)
      diabetes mellitus. METHODS: We studied 30 Type II diabetic patients with
      symptomatic erectile dysfunction and 30 potent diabetic patients matched for age
      and disease. Endothelial functions were assessed with the L-arginine test, plasma
      thrombomodulin and cell adhesion molecules circulating concentrations.
      Haemostasis was evaluated with markers of thrombin activation and fibrinolysis.
      Quantitative sensory testing (vibratory, warming, and heat-pain thresholds),
      cardiovascular reflex tests and 24-h blood pressure monitoring were used to
      assess peripheral or autonomic neuropathy. RESULTS: Mean erectile score and HbA1c
      were 10.5+/-5.8 and 8.3+/-1.6% in patients with erectile dysfunction, and 24.0+/
      0.7 and 6.8+/-1.4% in those without erectile dysfunction, respectively (p <
      0.001); there was a significant relation between HbA1c and erectile function
      score in patients with erectile dysfunction (r = -0.45, p = 0.02). The decrease
      in blood pressure and platelet aggregation in response to L-arginine was lower (p
      < 0.05-0.02) in patients with erectile dysfunction, whereas soluble
      thrombomodulin, P-selectin and intercellular cell ahhesion molecule-1
      concentrations were higher (p < 0.05-0.02). Indices of coagulation activation (F1
      + 2 and D-dimers) and reduced fibrinolysis (PAI-1) were also found to be higher
      in erectile dysfunction patients. Heat-pain and warm perception thresholds. as
      well as cardiovascular reflex tests, were most commonly abnormal in patients with
      erectile dysfunction (p < 0.05). In multivariate analysis, HbA1c, MBP response to
      L-arginine, P-selectin, indices of coagulation, and quantitative sensory testing
      were independent predictors of erectile function score.
      CONCLUSION/INTERPRETATION: Erectile dysfunction in diabetic men correlates with
      endothelial dysfunction. A reduced nitric oxide activity might provide a unifying
      explanation.

PMID- 11596672
TI  - Effect of the hydroxyl radical scavenger, dimethylthiourea, on peripheral nerve
      tissue perfusion, conduction velocity and nociception in experimental diabetes.
AB  - AIMS/HYPOTHESIS: Increased oxidative stress has been linked to diabetic
      neurovascular complications, which are reduced by antioxidants. Our aim was to
      assess the contribution of hydroxyl radicals to early neuropathic changes by
      examining the effects of treatment with the specific scavenger, dimethylthiourea,
      on nerve function and neural tissue blood flow in diabetic rats. METHODS:
      Diabetes was induced by streptozotocin. Measurements comprised sciatic nerve
      motor and saphenous nerve sensory conduction velocity. Responses to noxious
      mechanical and thermal stimuli were estimated by Randall-Sellito and Hargreaves
      tests respectively. Sciatic nerve and superior cervical ganglion blood flow were
      measured by hydrogen clearance microelectrode polarography. RESULTS: Eight weeks
      of diabetes reduced motor and sensory conduction velocity by 19.9% and 15.7%
      respectively, and these were completely corrected by 2 weeks of dimethylthiourea
      treatment. The ED50 for motor conduction was 9 mg kg(-1) x day(-1). Mechanical
      and thermal nociceptive sensitivities were 18.9% and 25.0% increased by diabetes,
      respectively, indicating hyperalgesia which was 70% reduced by dimethylthiourea.
      Sciatic endoneurial and superior cervical ganglion blood flows were 51.2% and
      52.4% reduced by diabetes and there was an approximately 80% improvement with
      treatment. CONCLUSION/INTERPRETATION: Hydroxyl radicals seem to make a major
      contribution to neuropathy and vasculopathy in diabetic rats. Treatment with the
      hydroxyl scavenger, dimethylthiourea, was highly effective. The data suggest that
      the development of potent hydroxyl radical scavengers suitable for use in man
      could markedly enhance the potential therapeutic value of an antioxidant approach
      to the treatment of diabetic neuropathy and vascular disease.

PMID- 11596673
TI  - Studies of the Pro12Ala polymorphism of the peroxisome proliferator-activated
      receptor-gamma2 (PPAR-gamma2) gene in relation to insulin sensitivity among
      glucose tolerant caucasians.
AB  - AIMS/HYPOTHESIS: We examined whether the Pro12-Ala polymorphism of the human
      peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene was related
      to altered insulin sensitivity among glucose-tolerant subjects or a lower
      accumulated incidence or prevalence of IGT and Type II (non-insulin-dependent)
      diabetes mellitus among Scandinavian Caucasians. METHODS: The Pro12Ala
      polymorphism was examined using PCR-RFLP Whole-body insulin sensitivity measured
      under hyperinsulinaemic-euglycaemic conditions was estimated in a population
      based sample of 616 glucose tolerant Swedish Caucasian men at age 70. In
      addition, insulin sensitivity index was measured using IVGTT and Bergman minimal
      modelling in a population-based sample of 364 young healthy Danish Caucasians.
      Finally, we evaluated whether the polymorphism predicted Type II diabetes and IGT
      in 841 seventy-year-old Swedish men. A case-control study was carried out in 654
      unrelated Danish Type II diabetic patients and 742 Danish glucose tolerant
      subjects matched for age and sex. RESULTS: Whole-body insulin sensitivity was
      significantly improved in carriers compared with non-carriers of the Ala-allele
      of the codon 12 polymorphism in Swedish Caucasian men (6.0+/-2.5 vs 5.6+/-2.5 mg
      kg(-1) x min(-1) x mU/l](-1) x 100, p = 0.044). The same tendency, but not
      significant, was observed in the insulin sensitivity index among the group of
      young healthy Danish Caucasians. The incidence of Type II diabetes and IGT among
      the Swedish subjects at the age of 70 was similar in the three genotype-groups of
      the Pro12Ala variant and the Ala-allele was not related to a lower prevalence of
      Type II diabetes in Danish Caucasians. CONCLUSION/INTERPRETATION: The Ala-allele
      of the PPAR-gamma2 polymorphism is associated with improved whole body insulin
      sensitivity among Swedish Caucasians.

PMID- 11596674
TI  - The paraoxonase PON1 promoter polymorphism C(-107)T is associated with increased
      serum glucose concentrations in non-diabetic patients.
AB  - AIMS/HYPOTHESIS: Oxidative stress could contribute to diabetes and its
      complications by predisposing to insulin resistance. Lipid peroxidation products
      are thought to be one mechanism involved in reduced insulin sensitivity. The
      serum enzyme, paraoxonase-1, protects lipoprotein lipids from oxidation. We
      examined the hypothesis that paraoxonase-1 could be associated with abnormal
      serum glucose concentrations in non-diabetic patients. METHODS: Serum paraoxonase
      1 activities and concentrations, as well as paraoxonase-1 gene polymorphisms,
      were analysed as a function of fasting glucose concentrations in non-diabetic
      patients and in Type II (non-insulin-dependent) diabetic patients. RESULTS: Serum
      paraoxonase-1 activities and concentrations were lower (p <0.05) in non-diabetic
      patients with abnormal fasting glucose concentrations. It was due to a higher
      frequency of low expressor paraoxonase-1 promoter genotypes in patients with
      abnormal glucose control. Promoter polymorphisms were independent determinants of
      abnormal fasting glucose concentrations. Low expressor genotypes were associated
      with higher glucose concentrations in non-diabetic patients (p = 0.046) and a
      trend to higher concentrations in Type II diabetic patients. The coding region
      paraoxonase-1 polymorphisms L55 M and Q192R was not associated with differences
      in fasting glucose. CONCLUSION/INTERPRETATION. The promoter polymorphism C(-107)T
      is a marker for abnormal fasting glucose concentrations in non-diabetic patients.
      It could indicate an active role for paraoxonase-1, possibly pre-disposing to
      insulin resistance, or linkage of paraoxonase-1 polymorphisms with other gene
      products implicated in glucose metabolism.

PMID- 11596675
TI  - Insulin binding monitored by fluorescence correlation spectroscopy.
AB  - AIM/HYPOTHESIS: The characteristics of insulin binding to its receptors have been
      extensively studied by the radioligand binding assay. We used fluorescence
      correlation spectroscopy to determine the distribution of diffusion times and
      further novel data on the kinetics of insulin's binding to its receptor. METHODS:
      Cultured human renal tubular cells (HRTC) were incubated with tetramethyl
      rhodamine labelled insulin (Rh-Ins) for 60 min. Fluorescence intensity
      fluctuations and autocorrelation functions for Rh-Ins, free in the incubation
      medium and bound to the cell membrane, were studied at single-molecule detection
      sensitivity in a 0.2 fL confocal volume. RESULTS: Measurements at the cell
      membrane revealed Rh-Ins binding with at least two diffusion components
      (diffusion times tauD1 = 0.8 ms, tauD2 = 20 ms) and corresponding weight
      fractions of y1 = 0.43 and y2 = 0.42. Specificity of the binding was shown by the
      dislocation of bound Rh-Ins when excess unlabelled insulin was added. Scatchard
      analysis showed a nonlinear plot, revealing two binding processes with different
      affinities (Kass approximately 2 x 10(10) M(-1) and approximately 1 x 10(9) M(
      1), respectively). CONCLUSION/INTERPRETATION: The fluorescence correlation
      spectroscopy results show two classes of binding sites with different affinities
      for insulin, or interactions between receptor sites consistent with negative
      cooperativity. This conclusion is in agreement with studies of insulin binding
      using radioligand binding assays. Because of its high sensitivity (single
      molecule detection), FCS, provides additional data allowing a more precise
      evaluation of the kinetics of ligand-receptor interactions at low expression
      levels in living cells.

PMID- 11596676
TI  - The LEW.1AR1/Ztm-iddm rat: a new model of spontaneous insulin-dependent diabetes
      mellitus.
AB  - AIMS/HYPOTHESIS: We describe a new Type I (insulin-dependent) diabetes mellitus
      rat model (LEW.1AR1/Ztm-iddm) which arose through a spontaneous mutation in a
      congenic Lewis rat strain with a defined MHC haplotype (RT1.Aa B/Du Cu). METHODS:
      The development of diabetes was characterised using biochemical, immunological
      and morphological methods. RESULTS: Diabetes appeared in the rats with an
      incidence of 20 % without major sex preference at 58+/-2 days. The disease was
      characterised by hyperglycaemia, glycosuria, ketonuria and polyuria. In
      peripheral blood, the proportion of T lymphocytes was in the normal range
      expressing the RT6.1 differentiation antigen. Islets were heavily infiltrated
      with B and T lymphocytes, macrophages and NK cells with beta cells rapidly
      destroyed through apoptosis in areas of insulitis. CONCLUSION/INTERPRETATION:
      This Type I diabetic rat develops a spontaneous insulin-dependent autoimmune
      diabetes through beta cell apoptosis. It could prove to be a valuable new animal
      model for clarifying the mechanisms involved in the development of autoimmune
      diabetes.

PMID- 11596677
TI  - Paternal insulin resistance and fetal growth: problem for the 'fetal insulin' and
      the 'fetal origins' hypotheses.

PMID- 11596678
TI  - Dietary microbial toxins and type 1 diabetes--a new meaning for seed and soil.

PMID- 11596680
TI  - One hundred years of Nobel Prize and diabetes.

PMID- 11596679
TI  - G972R polymorphism of IRS-1 in women with polycystic ovary syndrome.

PMID- 11596681
TI  - Where winds the road of distance education in nursing?

PMID- 11596682
TI  - Professional socialization of baccalaureate nursing students: can students in
      distance nursing programs become socialized?
AB  - Distance education programs may have difficulty socializing nursing students due
      to limited face-to-face student-faculty interaction. Socialized attitudes toward
      the nursing profession were assessed using two measures with three groups--senior
      BSN students enrolled at campus-based programs, senior BSN students enrolled in
      distance programs, and non-nursing students. The purpose of this analysis was to
      determine whether nursing students enrolled in distance programs had professional
      socialization outcomes comparable to nursing students enrolled in campus-based
      programs, and to examine the psychometric properties of two popular measures of
      professional socialization. Results indicated that students in the distance
      programs had higher scores than the campus-based nursing students, who, in turn,
      had higher scores than non-nursing students. A statistical interaction of RN
      status by program type indicated that health care experience was a critical
      factor in the socialization process. Of the two socialization measures examined,
      one had acceptable psychometric properties. These data suggest that health care
      and preceptorship experiences are important determinants of professional
      socialization and that students who opt for distance nursing programs graduate
      with socialization outcomes that are at least comparable to those of students who
      attend traditional programs.

PMID- 11596683
TI  - Informatics competencies for nurses at four levels of practice.
AB  - Valid and comprehensive nursing informatics (NI) competencies currently are
      lacking. Meanwhile, nursing leaders are emphasizing the need to include NI in
      nursing curricula, as well as within the roles of practicing nurses in all
      settings. This article presents the initial work of a team of NI experts toward
      development of a valid and reliable set of NI competencies. Previous work
      primarily has focused on computer-related skills, rather than examining a broad
      definition of informatics competencies. For this current work, NI competencies
      encompass all skills, not only computer-related skills, as well as knowledge and
      attitudes needed by nurses. The first two authors created a database of NI
      competencies from the existing literature. A larger panel of NI experts then
      affirmed, modified, added, or deleted competencies from this database.
      Competencies were placed into four distinct skill levels. Definitions of each
      skill level and an initial master list of competencies are provided.

PMID- 11596684
TI  - Perspective transformation in RN-to-BSN distance education.
AB  - This study examines perspective transformation (or professional resocialization)
      in RN-to-BSN students obtaining their degree by distance education. A
      socialization scale was used to compare newly admitted and graduating RN-to-BSN
      students who had taken their courses onsite, by distance education, or a mixture
      of the two methods. The scores of entering and graduating RN-to-BSN students also
      were compared to those of graduates from the generic program to identify if
      program and experience are factors in scores achieved. Results indicate that all
      BSN graduates had significantly higher scores than the diploma-prepared nurses
      entering the RN-to-BSN program. RN-to-BSN graduates who had used distance
      education had the highest scores, followed by the onsite RN-to-BSN students.
      Students who had taken a mixture of distance and onsite courses had scores
      similar to those of generic program graduates. Experience and full-time
      employment status were significantly associated with higher scores among
      graduating RN-to-BSN students. Implications for nurse educators working with RN
      to-BSN students who use distance education are discussed.

PMID- 11596685
TI  - Computer versus lecture: a comparison of two methods of teaching oral medication
      administration in a nursing skills laboratory.
AB  - The purpose of this study was to compare the effectiveness of both an
      interactive, multimedia CD-ROM and a traditional lecture for teaching oral
      medication administration to nursing students. A randomized pretest/posttest
      experimental design was used. Forty-two junior baccalaureate nursing students
      beginning their fundamentals nursing course were recruited for this study at a
      large university in the midwestern United States. The students ranged in age from
      19 to 45. Seventy-three percent reported having average computer skills and
      experience, while 15% reported poor to below average skills. Two methods were
      compared for teaching oral medication administration--a scripted lecture with
      black and white overhead transparencies, in addition to an 18-minute videotape on
      medication administration, and an interactive, multimedia CD-ROM program,
      covering the same content. There were no significant (p < .05) baseline
      differences between the computer and lecture groups by education or computer
      skills. Results showed significant differences between the two groups in
      cognitive gains and student satisfaction (p = .01), with the computer group
      demonstrating higher student satisfaction and more cognitive gains than the
      lecture group. The groups were similar in their ability to demonstrate the skill
      correctly. Importantly, time on task using the CD-ROM was less, with 96% of the
      learners completing the program in 2 hours or less, compared to 3 hours of class
      time for the lecture group.

PMID- 11596686
TI  - Safety net: student exchange learning and supervision on the World Wide Web.

PMID- 11596687
TI  - Natriuretic peptide approved for use in decompensated CHF.

PMID- 11596688
TI  - Abbott files NDA, will continue to distribute synthroid.

PMID- 11596689
TI  - VIPPS program suspends online pharmacy.

PMID- 11596690
TI  - Health centers receive grants to provide, improve pharmaceutical services.

PMID- 11596692
TI  - Health-related web-site accreditation program gets under way.

PMID- 11596693
TI  - ASHP foundation announces literature-contribution awards.

PMID- 11596691
TI  - New bisphosphonic acid approved by FDA.

PMID- 11596694
TI  - Caspofungin acetate, bivalirudin.

PMID- 11596696
TI  - Data analyst technician: an innovative role for the pharmacy technician.
AB  - The development of an innovative role for the pharmacy technician is described.
      The role of the pharmacy technician was based on a needs assessment and the
      expertise of the pharmacy technician selected. Initial responsibilities of the
      technician included chart reviews, benchmarking surveys, monthly financial impact
      analysis, initiative assessment, and quality improvement reporting. As the drug
      use and disease-state management (DUDSM) program expanded, pharmacist activities
      increased, requiring the expansion of data analyst technician (DAT) duties. These
      new responsibilities included participation in patient assessment, data
      collection and interpretation, and formulary enforcement. Most recently,
      technicians' expanded duties include maintenance of a physician compliance
      profiling database, quality improvement reporting and graphing, active role in
      patient risk assessment and database management for adult vaccination, and
      support of financial impact monitoring for other institutions within the health
      system. This pharmacist-technician collaboration resulted a threefold increase in
      patient assessments completed per day. In addition, as the DUDSM program
      continues to expand across the health system, an increase in DAT resources from
      0.5 to 1.0 full-time equivalent was obtained. The role of the DAT has increased
      the efficiency of the DUDSM program and has provided an innovative role for the
      pharmacy technician.

PMID- 11596695
TI  - Abuse of Coricidin HBP cough & cold tablets: episodes recorded by a poison
      center.
AB  - Cases involving ingestion of a dextromethorphan-containing product recorded at a
      poison control center were studied. A retrospective review of all consultations
      involving the ingestion of Coricidin HBP Cough & Cold tablets recorded by the
      California Poison Control System was conducted for the period from January 1 to
      October 1, 2000. Computerized charts on the consultations were reviewed to obtain
      data on patient age and sex, number of tablets taken, reason for tablet
      ingestion, symptoms, treatment, disposition, and outcome. A total of 92 charts
      (for 92 patients) documenting Coricidin HBP Cough & Cold tablet ingestion were
      reviewed. The reason for tablet ingestion was classified as abuse in 65 patients
      (71%), a suicide attempt in 8 (9%), misuse in 1 (1%), malicious administration in
      1 (1%), and normal use (but with an adverse drug reaction) in 1 (1%); 16 patients
      (17%) consumed the tablets for an unknown reason. The 92 patients comprised 42
      males and 50 females. Among all patients, 78 (85%) were 13-17 years old, and
      among those classified as having abusive intent, 58 (89%) were in the same age
      range. The most commonly reported signs and symptoms associated with ingestion
      were tachycardia (50 patients), hypertension (29), lethargy (40), mydriasis (20),
      agitation (15), ataxia or dizziness (20), and vomiting (9). Sixty-one patients
      (66%) had some alteration in mental status. Fifty-six (61%) were treated in the
      emergency department; 11 (12%) were admitted. All patients recovered completely.
      Information on the ingestion of Coricidin HBP Cough & Cold tablets recorded at a
      poison control center indicated a high rate of abuse of the product among
      teenagers.

PMID- 11596697
TI  - Ultrashort regimen of lansoprazole-amoxicillin-azithromycin for eradicating
      Helicobacter pylori.
AB  - The efficacy and safety of two ultrashort azithromycin-containing regimens for
      Helicobacter pylori infection were studied. Patients positive for H. pylori
      infection were assigned to receive either a three-day drug regimen (group A) or a
      five-day regimen (group B). In both groups, patients received lansoprazole 30 mg
      p.o. twice daily on day 1 and, on days 2 and 3, lansoprazole 30 mg p.o. twice
      daily, amoxicillin 1 g (of anhydrous amoxicillin) p.o. twice daily, and
      azithromycin 500 mg (of anhydrous azithromycin) p.o. twice daily. Group B
      patients received lansoprazole 30 mg p.o. twice daily and amoxicillin 1 g p.o.
      twice daily for two additional days. Gastric biopsy specimens were subjected to
      culture and susceptibility testing. A minimum of four weeks after the completion
      of therapy, the patients underwent a 14C-urea breath test to determine whether H.
      pylori had been eradicated. A total of 28 patients were enrolled (15 in group A
      and 13 in group B). Treatment was well tolerated. H. pylori was eradicated in 4
      (36%) of 11 patients in group A and 2 (22%) of 9 group B patients (26.6% and
      15.4%, respectively, in intention-to-treat analysis). None of the isolates of H.
      pylori showed resistance to amoxicillin or clarithromycin. Regimens consisting of
      lansoprazole plus two or four days of azithromycin and amoxicillin therapy
      eradicated H. pylori in 36% and 22% of patients, respectively.

PMID- 11596698
TI  - Practitioner versus medication-expert opinion on psychiatric pharmacotherapy of
      mentally retarded patients with mental disorders.
AB  - The agreement of practicing psychiatrists with medication experts regarding how
      psychotropic drugs should be used to treat behavioral and psychiatric problems in
      patients with mental retardation was studied. The medication survey used in
      developing guidelines on the treatment of behavioral and psychiatric problems in
      mental retardation was sent to 85 psychiatrists who had been identified as caring
      for the mentally retarded in the Texas public mental health system. The
      comparison of these practitioners with the medication experts included first-line
      and second-line treatment choices. Survey analysis was based on using 95%
      confidence intervals (CIs) to determine the type of rating. If the 95% CIs for
      the practitioners' responses overlapped the 95% CIs for experts, the two groups
      were judged to be in agreement. Thirty-seven practitioners (43.5%) completed and
      returned the survey. Few differences between the practitioners and the medication
      experts were found with respect to treatments for specific mental illness
      diagnoses. However, the practitioners rated venlafaxine and mirtazapine higher
      than the medication experts. Lithium augmentation of therapy with selective
      serotonin-reuptake inhibitors for nonpsychotic depression was rated first-line by
      the practitioners and second-line by the medication experts. Practicing
      psychiatrists and medication experts generally agreed about the use of
      psychotropic drugs for mental illness in patients with mental retardation.

PMID- 11596699
TI  - Computerized controlled-substance surveillance: application involving automated
      storage and distribution cabinets.
AB  - A secondary data-reporting system used to scan the archives of a hospital's
      automated storage and distribution cabinets (ASDCs) for indications of controlled
      substance diversion is described. ASDCs, which allow access to multiple doses of
      the same medication at one time, use drug count verification to ensure complete
      audits and disposition tracking. Because an ASDC may interpret inappropriate
      removal of a medication as a normal transaction, users of ASDCs should have a
      comprehensive plan for detecting and investigating controlled-substance
      diversion. Monitoring for and detecting diversion can be difficult and time
      consuming, given the limited report-generating features of many ASDCs. Managers
      at an 800-bed hospital used report-writing software to address these problems.
      This application interfaces with the hospital's computer system and generates
      customized reports. The monthly activity recapitulation report lists each user of
      the ASDCs and gives a summary of all the controlled-substance transactions for
      those users for the time period specified. The monthly summary report provides
      the backbone of the surveillance system and identifies situations that require
      further audit and review. This report provides a summary of each user's activity
      for a specific medication for the time period specified. The detailed summary
      report allows for efficient review of specific transactions before there is a
      decision to conduct a chart review. This report identifies all ASDC controlled
      substance transactions associated with a user. A computerized report-generating
      system identifies instances of inappropriate removal of controlled substances
      from a hospital's ASDCs.

PMID- 11596700
TI  - Retrospective analysis of mortalities associated with medication errors.
AB  - The types, causes, contributing factors, and patient demographics of fatal
      medication errors were reviewed. Case reports of medication errors from
      hospitals, ambulatory care settings, and patients' homes that were entered in
      FDA's Adverse Event Reporting System during 1993-98 were the source of
      information on fatal medication errors. Each report was classified using
      predefined criteria and a taxonomy developed by the National Coordinating Council
      for Medication Error Reporting and Prevention. The types, causes, contributing
      factors, and patient demographics were identified, and the causality of each case
      was assessed to prevent future fatalities. The data indicated 5,366 medication
      error reports. Fifty-nine reports were excluded and classified as duplicate
      reports or intentional overdoses. Of the remaining medication error reports,
      68.2% resulted in serious patient outcomes and 9.8% were fatal. Of the 469 fatal
      medication error reports, 48.6% occurred in patients over 60 years. The most
      common types of errors resulting in patient death involved administering an
      improper dose (40.9%), administering the wrong drug (16%), and using the wrong
      route of administration (9.5%). The most common causes of errors were performance
      and knowledge deficits (44%) and communication errors (15.8%). Fatal medication
      errors accounted for approximately 10% of medication errors reported to FDA and
      were most frequently the result of improper dosing of the intended drug and
      administration of an incorrect drug. A review of case reports of medication
      errors from 1993 to 1998 yielded information on the most frequent causes of and
      contributing factors involved in fatal medication errors.

PMID- 11596701
TI  - Telephone service for providing consumers with information on herbal supplements.

PMID- 11596702
TI  - Patterns of physician-reported diagnoses for women receiving raloxifene
      prescriptions.

PMID- 11596703
TI  - Stability of tirofiban hydrochloride in 0.9% sodium chloride injection for 30
      days.

PMID- 11596704
TI  - Implementing an inpatient pharmacy-based pneumococcal vaccination program.

PMID- 11596705
TI  - Counseling patients about drug allergies in the inpatient setting.

PMID- 11596706
TI  - Possibilities.

PMID- 11596707
TI  - The path to paradise: Dante's vision for pharmacy's future.

PMID- 11596708
TI  - Editorial: The United Nations General Assembly special session on HIV/AIDS:
      'global crisis--global action'.

PMID- 11596709
TI  - OzFoodNet: enhancing foodborne disease surveillance across Australia: quarterly
      report January to March 2001.

PMID- 11596710
TI  - Annual report of the National Influenza Surveillance Scheme, 2000.
AB  - Surveillance of influenza in Australia in 2000 was based on data from national
      and state-based sentinel general practice consultations for influenza-like
      illness, laboratory isolations of influenza virus and absenteeism rates from a
      national employer. The peak in influenza cases was in mid-September. Influenza A
      was the dominant strain, with the highest proportion being influenza A (H3N2),
      but with a significant proportion of isolates of influenza A (H1N1) (16%) for the
      first time since 1995. The influenza A (H3N2) isolates were predominantly related
      to A/Moscow/10/99 and vaccine strain A/Panama/2007/99. Influenza A (H1N1) was
      predominantly A/New Caledonia/20/99. The proportion of Influenza B viruses
      isolated also increased in keeping with a three-yearly cycle of influenza B
      epidemics in Australia. influenza B isolates showed a progressive drift away from
      the B/Beijing/184/93 strain with the majority closely related to the
      B/Sichuan/379/99 strain. In 2000, influenza vaccination levels reached 74 per
      cent in persons aged over 65 years.

PMID- 11596711
TI  - Annual report of the Australian Meningococcal Surveillance Programme, 2000.
AB  - The National Neisseria Network has undertaken meningococcal isolate surveillance
      by means of a collaborative laboratory based initiative since 1994. The phenotype
      (serogroup, serotype and serosubtype) and antibiotic susceptibility of 388
      isolates of Neisseria meningitidis from invasive cases of meningococcal disease
      were determined in 2000. More than 90 per cent of the invasive isolates were
      either serogroup B or C. There was however, considerable diversity in the
      phenotypes circulating in the different States and Territories. Serogroup B
      strains predominated in all jurisdictions except Victoria and were isolated from
      sporadic cases of invasive disease. Serogroup B phenotypes were generally
      disparate although phenotypes B:15:P1.7 and B:4:P1.4 were widely distributed. The
      latter remained especially prominent in New South Wales. The number and
      proportion of serogroup C isolates again increased in Victoria compared with
      previous years. Infections with a novel phenotype that was first noted in 1999,
      C:2a:P1.4(7), were common in Victoria, especially in adolescents and adults, but
      rarely seen elsewhere in Australia. Phenotype C:2a:P1.2, was also noted in the
      preceding year and continued to be seen in Victoria in 2000 but was infrequently
      encountered in other jurisdictions. Serogroup C infections remained common in New
      South Wales where phenotype C:2a:P1.5 was regularly isolated. About two thirds of
      all isolates showed decreased susceptibility to the penicillin group of
      antibiotics (MIC 0.06 to 0.5 mg/L). All isolates tested were susceptible to third
      generation cephalosporins and to the prophylactic agents rifampicin and
      ciprofloxacin. Data relating to 147 laboratory-confirmed but culture-negative
      cases, supplemented information on culture-confirmed cases in this report. Some
      differences in the patterns of disease were revealed when culture-based and non
      culture-based data were compared.

PMID- 11596712
TI  - An outbreak of serogroup C meningococcal disease associated with a secondary
      school.
AB  - An outbreak of 3 cases of invasive meningococcal disease occurred in a secondary
      school on 2 campuses in Victoria. Despite having only one isolate (a C.2a:nst
      strain), meningococcal DNA was identified by polymerase chain reaction (PCR) in
      early culture-negative blood specimens of the other 2 cases. Both were
      subsequently shown by PCR to be capsule serogroup C by PCR. An committee was
      formed to manage the response to the outbreak. Chemoprophylaxis was offered to
      family and children who had been in close contact with the cases. As one strain
      had been confirmed as being of a vaccine-preventable group, vaccination was
      offered to the whole school community as well as the families of cases. The
      direct costs of the outbreak to public health, which would have been identical
      whatever the causative serogroup, was $8,178. Vaccine charges accounted for most
      of the additional $56,941 cost of vaccinating the target group of 1600 students,
      staff, and families. No further cases have been associated with this outbreak.

PMID- 11596713
TI  - Editorial: Meningococcal disease.

PMID- 11596714
TI  - Measles immunity among young adults in Victoria.
AB  - Measles outbreaks in Victoria in 1999 and 2001 have suggested that a substantial
      proportion of young Victorian adults may be susceptible to measles infection. We
      performed a serosurvey of 300 18-30-year-old healthy blood donors and 312 sera
      retrieved after diagnostic testing for a non-rash illness in patients of the same
      age group, with the aim of estimating the proportion of young adults in Victoria
      immune to measles. We also aimed to define more precisely the birth cohorts at
      risk of measles infection, with cohorts reflecting the measles immunisation
      policies of previous years. There was no significant difference in measles
      immunity between the 300 blood donors (79.0%, 95% confidence interval 73.9-83.5)
      and the 312 patients whose sera had been stored (84.0%, 95% CI 79.4-87.9,
      p=0.11). There was, however, a significant difference in immunity by birth
      cohort. In the combined results from both samples, the proportion of people born
      between 1968 and 1974 who were immune to measles was 88.4 per cent (95% CI 84.1
      91.6) while the proportion of those born between 1975 and 1981 was 74.1 per cent
      (95% CI 68.7-79.1). This study confirms that a substantial proportion of young
      Victorian adults are susceptible to measles, but also demonstrates that those
      born between 1975 and 1981 are more likely to be non-immune than those born
      before 1975. A review of published Australian data supports this conclusion and
      confirms the need for a measles control program aimed at young adults.

PMID- 11596715
TI  - Measles immunity in young Australian adults.
AB  - Previous state-based serosurveys and recent outbreaks have indicated that young
      adults may be at risk of measles. To provide a national picture of immunity in
      adults, we tested 2126 sera from 19-49 year olds that had been opportunistically
      collected from laboratories across Australia, between July 1996 and November
      1998. Sera were stratified into age groups based on expected levels of immunity.
      Sample numbers were proportional to the population size in each State and
      Territory. Immunity was determined using an anti-measles IgG enzyme immunoassay
      (EIA) according to the manufacturer's instructions. Results were compared with
      those on sera from 2 groups of 1-18 year olds; one group collected before the
      Measles Control Campaign (conducted in the second half of 1998) and the other
      group collected after the Campaign. Immunity was highest (98.3%) in subjects aged
      at least 30 years (born before 1968) reflecting greater exposure to the measles
      virus in these older subjects. Immunity was lowest in those aged 1-6 years (born
      in 1994-8; 83.6%) and 18-22 years (born in 1974-80; 88.9%). The relatively low
      level of immunity in 18-22 year olds is probably due to lower vaccination
      coverage in this group compared with younger cohorts (aged 6-17 years). These
      results indicate the ongoing need to improve vaccine uptake in infants and
      suggest that a vaccination campaign targeting young adults would be beneficial.

PMID- 11596716
TI  - Measles: how many hospitalised cases are we missing?
AB  - We aimed to determine whether the Victorian measles surveillance system had
      missed hospitalised cases of measles during an inter-epidemic period. We searched
      the Victorian Inpatient Minimum Dataset (VIMD) for the period 1 January 1997 to
      30 June 1998 to identify patients with ICD-9 discharge codes for measles (055).
      The data were compared with that held in the Victorian measles surveillance
      dataset. The hospital case notes of patients identified in the VIMD but not in
      the measles surveillance dataset were reviewed systematically to determine
      whether the patients met case definitions for laboratory-confirmed or clinically
      compatible measles. Sixteen admissions (15 patients) were identified with a
      measles ICD-9 code. Eight patients were not identified in the measles
      surveillance dataset. Of these, one was a laboratory confirmed case of measles
      and two met a clinical case definition but all should have been notified to the
      Department of Human Services as suspected cases. While the small number of missed
      notifications is encouraging in terms of overall measles surveillance, it
      highlights important deficiencies in the awareness of hospital staff of their
      role in the control of measles, particularly as Australia moves towards the
      elimination of measles.

PMID- 11596717
TI  - Editorial: measles elimination in Australia.

PMID- 11596718
TI  - Report of the Australian Rotavirus Surveillance Program, 2000/2001.
AB  - The National Rotavirus Reference Centre together with 15 collaborating
      laboratories Australia-wide conducted rotavirus surveillance from June 1999. The
      serotypes of rotaviruses that are responsible for the hospitalisation of children
      with acute diarrhoea were determined for the period June 2000 to May 2001. We
      examined 1108 rotavirus specimens using a combination of monoclonal antibody
      immunoassay, reverse transcription-PCR, and Northern hybridisation. Serotype G1
      strains were the most prevalent overall (49.5%), and found in all centres.
      Serotype G9 rotaviruses, which were first identified in 1997, were second in
      importance (18.1%). Serotype G2 viruses were next (12.5%), followed by the re
      emergence of serotype G4 viruses (9.7%). The findings of this study have
      implications for vaccine development strategies where protection against
      serotypes additional to G1-G4 may be required.

PMID- 11596719
TI  - Epidemiology of malaria in Victoria 1999-2000: East Timor emerges as a new source
      of disease.

PMID- 11596720
TI  - Locally-acquired Plasmodium falciparum malaria on Darnley Island in the Torres
      Strait.

PMID- 11596721
TI  - Murray valley encephalitis.

PMID- 11596722
TI  - A case of Kunjin virus encephalitis in a traveller returning from the Northern
      Territory.

PMID- 11596723
TI  - Australian encephalitis: Sentinel Chicken Surveillance Programme.

PMID- 11596724
TI  - Communicable diseases surveillance.

PMID- 11596725
TI  - Editorial: Development of Australia's response to bovine spongiform
      encephalopathy and variant Creutzfeldt-Jakob disease.

PMID- 11596726
TI  - "Equine basal cell tumors: 6 cases (1985-1999)".

PMID- 11596727
TI  - Using foals with colic as controls was inappropriate.

PMID- 11596728
TI  - Problems in the canine left ventricular outflow tract.

PMID- 11596729
TI  - Usefulness of the indexed effective orifice area in the assessment of subaortic
      stenosis in the dog.
AB  - To evaluate the usefulness of the Doppler-derived effective orifice area (EOA) in
      assessing the hemodynamic severity of subaortic stenosis (SAS) in dogs, 2
      dimensional and Doppler echocardiographic examinations were performed in 16 dogs
      with SAS, 22 normal adult dogs, and 22 normal puppies. The EOA was calculated by
      the continuity equation using the stroke volume determined in the right
      ventricular outflow tract. The EOA was significantly lower (P < .001 ) in the SAS
      dogs (0.76+/-0.45 cm2) and in the normal puppies (1.58+/-1.00 cm2) than in the
      normal adult dogs (2.34+/-0.78 cm2). The EOA indexed for body surface area (IEOA)
      was significantly lower (0.89+/-0.48 cm2/m2) in SAS dogs than in the normal
      puppies (2.42+/-0.85 cm2/m2) or adults (2.22+/-0.76 cm2/m2). The normal dogs
      (adults and puppies) had an IEOA of > or =1.25 cm2/m2. Among the demographic and
      echocardiographic parameters measured in this study, only the indexed EOA was
      significantly associated (P = .03) with the occurrence of adverse events (eg,
      syncope, episodic weakness, ventricular arrhythmias). This study demonstrates the
      usefulness and feasibility of the indexed EOA as measured by Doppler
      echocardiography for noninvasive assessment of SAS severity in dogs.

PMID- 11596730
TI  - A review of coronavirus infection in the central nervous system of cats and mice.
AB  - Feline infectious peritonitis (FIP) is a common cause of death in cats.
      Management of this disease has been hampered by difficulties identifying the
      infection and determining the immunological status of affected cats and by high
      variability in the clinical, pathological, and immunological characteristics of
      affected cats. Neurological FIP, which is much more homogeneous than systemic
      effusive or noneffusive FIP, appears to be a good model for establishing the
      basic features of FIP immunopathogenesis. Very little information is available
      about the immunopathogenesis of neurologic FIP, and it is reasonable to use
      research from the well-characterized mouse hepatitis virus (MHV) immune-mediated
      encephalitis system, as a template for FIP investigation, and to contrast
      findings from the MHV model with those of FIP. It is expected that the
      immunopathogenic mechanisms will have important similarities. Such comparative
      research may lead to better understanding of FIP immunopathogenesis and rational
      prospects for management of this frustrating disease.

PMID- 11596731
TI  - The mixed acid-base disturbances of severe canine babesiosis.
AB  - Thirty-four dogs suffering from severe babesiosis caused by Babesia canis rossi
      were included in this study to evaluate acid-base imbalances with the
      quantitative clinical approach proposed by Stewart. All but 3 dogs were severely
      anemic (hematocrit <12%). Arterial pH varied from severe acidemia to alkalemia.
      Most animals (31 of 34; 91%) had inappropriate hypocapnia with the partial
      pressure of CO2 < 10 mm Hg in 12 of 34 dogs (35%). All dogs had a negative base
      excess (BE; mean of - 16.5 mEq/L) and it was below the lower normal limit in 25.
      Hypoxemia was present in 3 dogs. Most dogs (28 of 34; 82%) were hyperlactatemic.
      Seventy percent of dogs (23 of 33) were hypoalbuminemic. Anion gap (AG) was
      widely distributed, being high in 15, low in 12, and normal in 6 of the 33 dogs.
      The strong ion difference (SID; difference between the sodium and chloride
      concentrations) was low in 20 of 33 dogs, chiefly because of hyperchloremia.
      Dilutional acidosis was present in 23 of 34 dogs. Hypoalbuminemic alkalosis was
      present in all dogs. Increase in unmeasured strong anions resulted in a negative
      BE in all dogs. Concurrent metabolic acidosis and respiratory alkalosis was
      identified in 31 of 34 dogs. A high AG metabolic acidosis was present in 15 of 33
      dogs. The lack of an AG increase in the remaining dogs was attributed to
      concurrent hypoalbuminemia, which is common in this disease. Significant
      contributors to BE were the SID, free water abnormalities, and AG (all with P <
      .01). Mixed metabolic and respiratory acid-base imbalances are common in severe
      canine babesiosis, and resemble imbalances described in canine endotoxemia and
      human malaria.

PMID- 11596732
TI  - Serologic and molecular evidence of coinfection with multiple vector-borne
      pathogens in dogs from Thailand.
AB  - Forty-nine dogs from Thailand were evaluated for serologic evidence of exposure
      or polymerase chain reaction (PCR) evidence of infection with vectorborne
      pathogens, including Ehrlichia sp. (Ehrlichia canis, Ehrlichia chaffeensis,
      Ehrlichia equi, and Ehrlichia risticii), Bartonella vinsonii subsp. berkhoffi
      (Bvb), spotted fever group (SFG) rickettsiae (Rickettsia rickettsii), Typhus
      group (TG) rickettsiae (Rickettsia canada, Rickettsia prowazekii, and Rickettsia
      typhi), and Babesia sp. (Babesia canis and Babesia gibsonii). All study dogs had
      at least 1 of 3 entry criteria: fever, anemia, or thrombocytopenia. By
      immunofluorescence antibody (IFA) testing, seroreactivity was most prevalent to E
      chaffeensis (74%) and E canis (71%) antigens, followed by E equi (58%), Bvb
      (38%), E risticii (38%), R prowazekii (24%), B canis (20%), R rickettsii (12%), R
      canada (4%), and B gibsonii (4%) antigens. There was 100% concordance between E
      canis IFA and Western blot immunoassay (WI) for 35 of 35 samples; 2 samples were
      IFA and WI reactive only to E equi antigens. By PCR amplification, 10 dogs were
      found to be infected with E canis, 5 with Ehrlichia platys, and 3 with B canis.
      Sequencing of PCR products was undertaken to compare Ehrlichia strains from
      Thailand to strains originating from the United States. Partial DNA sequence
      analysis confirmed infection with E canis and E platys, with identical 16S rRNA
      sequence alignment to E canis (U26740) and to E platys (M83801), as reported in
      GenBank. Partial E canis P28.1 and P28.2 amino acid sequences from Thai dogs were
      divergent from analogous sequences derived from North American E canis (AF082744)
      strains, suggesting that the Thai dogs were infected with a geographically
      distinct strain of E canis compared to North American strains. The results of
      this study indicate that dogs in Thailand have substantial exposure to
      vectorborne diseases and that coinfection with these pathogens may be common.

PMID- 11596733
TI  - Postprandial venous ammonia concentrations in the diagnosis of hepatobiliary
      disease in dogs.
AB  - A postprandial ammonia tolerance test (PPATT) was performed on normal dogs and
      dogs with signs that suggested they may have liver disease. All dogs underwent
      transcolonic scintigraphy, liver biopsy, or both and were assigned to
      extrahepatic disease, primary hepatocellular, and congenital portosystemic
      vascular anomalies (PSVA) groups. Each dog was fed a chicken and rice diet
      providing 25% of its estimated daily metabolizable energy requirement (MER) as an
      ammonia challenge. This is practical in patients with liver disease because
      ammonium chloride administration often causes vomiting or ammonia toxicity.
      Venous ammonia concentrations were measured before feeding and every 2 hours
      after feeding for 8 hours. No difference in mean ammonia concentrations between
      dogs with extrahepatic disease and control dogs was found. Therefore, the
      specificity of the PPATT was 100%. Dogs with hepatocellular disease showed no
      change in mean ammonia concentration at any time point, before or after feeding,
      but sensitivity was greatest when venous ammonia was measured 6 hours after
      feeding (sensitivity before feeding, 28%, and after feeding, 36%). Among dogs
      with congenital PSVA, mean ammonia concentrations were higher than the reference
      range at all time points before and after feeding, and peak mean ammonia
      concentration occurred 6 hours after feeding. In this group, the sensitivity of
      the PPATT was 81% before feeding and 91% 6 hours after feeding. This study
      demonstrates that the measurement of venous ammonia concentration is a useful
      test to detect congenital PSVA, and the sensitivity of the test may be improved
      by sampling 6 hours after feeding. The PPATT has poor sensitivity in detecting
      primary hepatocellular disease.

PMID- 11596734
TI  - Evaluation of esophageal transit of tablets and capsules in 30 cats.
AB  - We have reported tablet-induced focal esophagitis and esophageal stricture
      formation in cats. The proposed mechanism is thought to be abnormal esophageal
      tablet retention resulting in focal esophagitis with subsequent stricture
      formation. The objective of this study was to evaluate the passage of tablets and
      capsules when given alone (dry swallow) and when followed by a water bolus (wet
      swallow) to determine if this could, in part, explain the esophageal stricture
      formation we have observed in cats. Fluoroscopy was used to evaluate tablet or
      capsule passage after administration. The percentage of dry tablet swallows that
      successfully passed into the stomach was 0.0% at 30 and 60 seconds, 6.7% at 90
      seconds, 13.3% at 120 seconds, 26.7% at 180 and 240 seconds, and 36.7% at 300
      seconds. Wet tablet swallows successfully passed 90.0% of the time at 30 seconds,
      93.3% of the time at 60 seconds, and 100.0% of the time thereafter. The
      percentage of dry capsule swallows that successfully passed was 16.7% at each
      time interval. Wet capsule swallows successfully passed 96.7% of the time at 30
      seconds and 100% of the time thereafter. For each time interval, wet swallows
      achieved significantly greater percentage passage into the stomach when compared
      to dry swallows (P < .05). This study shows that tablets or capsules given by dry
      swallow have prolonged retention in the esophagus compared to those given by wet
      swallow. On the basis of this study, we recommend the routine administration of a
      water bolus to cats receiving tablets or capsules PO to facilitate esophageal
      clearance. This practice may help prevent medication-associated esophagitis or
      stricture formation.

PMID- 11596735
TI  - Hematologic abnormalities and outcome of 16 cats with myelodysplastic syndromes.
AB  - We investigated the hematologic abnormalities and prognoses in 16 cats with
      myelodysplastic syndromes (MDS). Nonregenerative anemia, thrombocytopenia, and
      neutropenia were observed in 15, 13, and 4, respectively, of the 16 cats with
      MDS. Morphologic abnormalities characteristic of MDS included megaloblastoid
      rubricytes (9 cats), hyposegmentation of neutrophils (7 cats), nuclear
      abnormality of rubricytes (10 cats) and neutrophils (13 cats), and
      micromegakaryocytes (10 cats). Disease in these 16 cats was subclassified into
      refractory anemia (RA; 8 cats), RA with excess of blasts (RAEB; 5 cats), RAEB in
      transformation (RAEB in T; 1 cat), and chronic myelomonocytic leukemia (CMMoL; 2
      cats), according to the human French-American-British (FAB) classification. In
      the cats in which the clinical outcome was known, 3 of 6 cats with high blast
      cell count MDS, including RAEB, RAEB in T, and CMMoL, developed acute myeloid
      leukemia, but only 1 of 8 cats with low blast cell count MDS (RA) developed acute
      myeloid leukemia. Based on the Dusseldorf scoring system for the prognosis of
      human MDS, the survival times of the cats showing high scores (> or =3 points)
      were significantly shorter than those of the cats with low scores (<3 points).
      The FAB classification and Dusseldorf scoring system were considered to be useful
      for predicting the prognosis of feline MDS. Furthermore, 15 of the 16 cats with
      MDS in this study were infected with feline leukemia virus, indicating its
      possible etiologic role in the pathogenesis of feline MDS.

PMID- 11596736
TI  - Fat feeding increases equine heparin-released lipoprotein lipase activity.
AB  - The aim of this study was to establish the dose-response relationship between fat
      intake and heparin-released plasma lipoprotein lipase (LPL) activity in horses.
      Eight mature trotters were fed 4 rations with different fat levels (3.0, 5.0,
      7.7, or 10.8% fat in the dry matter) according to a 4 X 4 Latin square design.
      The experimental rations consisted of hay and different concentrates; the
      concentrates and hay were given in a 3:1 ratio on an energy basis. Soybean oil
      was added to the concentrates at the expense of isoenergetic amounts of glucose.
      Blood samples were taken at the end of each dietary period, which lasted 3 weeks.
      Fat feeding was found to increase heparin-released plasma LPL activity in a dose
      dependent fashion. When the data from this study and previous studies were
      combined it was calculated that an increase in fat intake by 1 g/kg dry matter is
      associated with an increase in LPL activity by 0.98 micromol fatty acid released
      mL(-1) x h(-1). Fat feeding raised the plasma concentrations of total
      cholesterol, high-density lipoprotein cholesterol, and phospholipids. Diet did
      not have a statistically significant effect on plasma triacylglycerol
      concentrations. The results are discussed in the light of the possible enhancing
      effect of fat feeding on the oxidative capacity of skeletal muscle.

PMID- 11596737
TI  - Iron deficiency in stabled Dutch warmblood foals.
AB  - Forty-three Dutch Warmblood foals were divided at random into 3 rearing groups
      immediately after birth: a box-rest group, a box-rest with exercise group, and a
      pasture group. All stabled foals (box-rest and exercise groups) were fed freshly
      cut grass harvested from the same pastures on which the pasture group foals were
      grazing. Blood samples were obtained monthly for CBC and biochemical analyses. At
      1-3 months of age, the foals at pasture were active but the foals in the box-rest
      and exercise groups were listless. Mean hemoglobin concentrations, PCVs, blood
      iron concentrations, and saturation of total iron binding capacity were
      significantly lower (P < .05) in the box-rest group (11.3+/-1.2 g/dL, 33+/-3%,
      123+/-67 microg/dL, and 18+/-9%) and the exercise group (11.6+/-1.5 g/dL, 34+/
      4%, 101+/-61 microg/dL, and 15+/-10%) compared with the pasture group (14.0+/-0.8
      g/dL, 42+/-3%, 212+/-67 microg/dL, and 32+/-10%). Oral supplementation of iron to
      all foals resulted in significant increases in the values of these variables in
      the box-rest group and exercise group at 4-5 months of age, and the stabled foals
      were as active as the foals at pasture. In the pasture group, no significant
      changes occurred. Management practices clearly influence the iron state in young
      growing foals from 1 to 3 months of age, and although not a frequent cause of
      anemia in the horse, an absolute deficit of body iron may occur in stabled foals
      fed freshly cut grass.

PMID- 11596738
TI  - Shetland Sheepdog leukodystrophy.
AB  - Three litters of Shetland Sheepdog pups born to the same bitch and 2 different
      sires were studied because of uncontrollable seizures or progressive neurologic
      dysfunction. Four pups from the 1st litter, 1 from the 2nd litter, and 4 from the
      3rd litter had severe diffuse spongy degeneration of the white matter of the
      brain and spinal cord. An inherited basis for this syndrome was suspected. The
      purpose of this study was to evaluate the pups with currently available screening
      tests for the metabolic, biochemical, infectious, and toxicologic causes of
      leukodystrophy seen in humans and animals. Computed tomography scans revealed
      diffuse hypomyelination in the affected pup. Complete postmortem examination,
      including histopathology and electron microscopy, delineated a leukodystrophy
      resembling human Canavan's disease, but amino acid and organic acid metabolism
      abnormalities were not detected. No etiology for Shetland Sheepdog leukodystrophy
      has been found, but this condition represents another familial disease in the
      purebred dog population.

PMID- 11596739
TI  - Successful treatment of intracranial abscesses in 2 horses.

PMID- 11596740
TI  - Cardiac troponin I in the normal dog and cat.
AB  - Cardiac troponin I (cTnI) has proven to be a highly specific and sensitive marker
      for myocardial cellular damage in many mammalian species. The structure of cTnI
      is highly conserved across species, and assays for human cTnI (including the one
      used in the current study) have been validated in the dog. Blood concentrations
      of cTnI rise rapidly after cardiomyocyte damage, and assay of cTnI potentially
      may be valuable in many clinical diseases. The purpose of this study was to
      establish the normal range of cTnI in heparinized plasma of dogs and cats. Forty
      one clinically normal dogs and 21 cats were included in the study. One to 3
      milliliters of blood were collected by venipuncture into lithium heparin
      vacutainers for analysis of cTnI (Stratusz CS). The range of plasma cTnI
      concentrations in dogs was <0.03 to 0.07 ng/mL with a mean of 0.02 ng/mL, with
      the upper tolerance limit (0.07 ng/mL) at the 90th percentile with 95%
      confidence. In cats, the range was <0.03 to 0.16 ng/mL with a mean of 0.04 ng/mL,
      and the upper tolerance limit (0.16 ng/mL) at the 90th percentile as well with
      90% confidence. This study establishes preliminary normal ranges of plasma cTnI
      in normal dogs and cats for comparison to dogs and cats with myocardial injury or
      disease.

PMID- 11596741
TI  - Substances with estrogenic activity in effluents of sewage treatment plants in
      southwestern Germany. 1. Chemical analysis.
AB  - A gas chromatography/mass spectrometry method for the simultaneous quantitative
      determination of natural and synthetic estrogens (17beta-estradiol, estrone,
      17alpha-ethinylestradiol, and mestranol), phytoestrogens (genistein and beta
      sitosterol), and xenoestrogens (benzyl butyl phthalate, dibutyl phthalate,
      bisphenol A, 4-nonylphenol [NP], 4-nonylphenoxyacetic acid [NP1EC], 4-nonylphenol
      diethoxylate [NP2EO], and alpha-endosulfan) in effluents of sewage treatment
      plants (STPs) was developed. Identification and quantification were carried out
      with the standard addition method using analyte-specific and, in some cases,
      deuterium-labeled internal standards. The effluents of 18 STPs were investigated.
      Apart from alpha-endosulfan and mestranol, all selected substances were detected
      in the majority of samples. The median concentrations of steroidal estrogens were
      between 0.4 ng/L (17alpha-ethinylestradiol) and 1.6 ng/L (17beta-estradiol). The
      metabolites of the nonylphenol polyethoxylates, NP, NPIEC, and NP2EO were found
      in concentrations ranging from the upper-ng/L-range (NP) to the lower-microg/L
      range (NP1EC). For all substances except mestranol and alpha-endosulfan, median
      values were calculated and compared to the results of other investigations in
      Europe and the United States. Possible dependencies of measured concentrations on
      the geographical location, the capacity, the influent composition, and the
      technical fitting of the STPs are discussed.

PMID- 11596742
TI  - Substances with estrogenic activity in effluents of sewage treatment plants in
      southwestern Germany. 2. Biological analysis.
AB  - The proliferation test with human estrogen receptor-positive MCF-7 breast cancer
      cells (E-Screen assay) was applied for quantitative determination of total
      estrogenic activity in 24-h composite effluent samples from 16 municipal and two
      industrial sewage treatment plants (STPs) in the state of Baden-Wurttemberg,
      southwestern Germany. The estrogenic efficacy relative to the positive control,
      17beta-estradiol, was between 26 and 74% (median, 48%) for the 16 municipal STPs.
      Estradiol equivalent concentrations (EEQs) were between 0.2 and 7.8 ng/L (median,
      1.6 ng/L) and, thereby, were lower than those found in a pilot study, which
      revealed EEQs of greater than 10 ng/L in the effluents of two other STPs. The
      EEQs in 14 of the 16 effluent samples were very similar (0.9-3.3 ng/L),
      indicating a rather constant input of estrogenic substances via STPs into rivers.
      Additional activated charcoal filtration turned out to be very efficient in
      further eliminating estrogenic activity from effluents. The EEQs of the E-Screen
      assay and those calculated from the results of extensive chemical analysis using
      the estradiol equivalency factors determined for 13 natural and synthetic
      estrogenic substances were comparable for most of the effluent samples. 17beta
      Estradiol, 17alpha-ethinylestradiol, and, to a lesser extent, estrone contributed
      to 90% or more of the EEQ value.

PMID- 11596743
TI  - Prediction of biodegradation from the atom-type electrotopological state indices.
AB  - A group contribution method based on atom-type electrotopological state indices
      for predicting the biodegradation of a diverse set of 241 organic chemicals is
      presented. Multiple linear regression and artificial neural networks were used to
      build the models using a training set of 172 compounds, for which the approximate
      time for ultimate biodegradation was estimated from the results of a survey of an
      expert panel. Derived models were validated by using a leave-25%-out method and
      against two test sets of 12 and 57 chemicals not included in the training set.
      The squared correlation coefficient (r2) for a linear model with 15 structural
      parameters was 0.76 for the training set and 0.68 for the test set of 12
      molecules. The model predicted correctly the biodegradation of 48 chemicals in
      the test set of 57 molecules, for which biodegradability was presented as rapid
      or slow. The use of artificial neural networks gave better prediction for both
      test sets when the same set of parameters was tested as inputs in neural network
      simulations. The predictions of rapidly biodegradable chemicals were more
      accurate than the predictions of slowly biodegradable chemicals for both the
      regression and neural network models.

PMID- 11596744
TI  - Trophic transfer and passive uptake of a polychlorinated biphenyl in experimental
      marine microbial communities.
AB  - To study the uptake mechanisms of 2,2',4,4',6,6'-hexachlorobiphenyl (HxCB 153) in
      microplankton with different feeding strategies, two laboratory communities were
      used. Trophic transfer of HxCB 153 was tested in a heterotrophic microbial food
      web consisting of bacteria, flagellates, and ciliates. Passive uptake was tested
      in a community consisting of algae and bacteria. The experiments were conducted
      over 6 d, and samples were retrieved daily. In the heterotrophic food web, a
      significant increase of the HxCB 153 concentration was observed in the top
      predator level (ciliates, p < 0.05), where the concentration doubled during the 3
      d of the experiment. A concomitant decrease was observed in the ciliate prey
      (flagellates), indicating that HxCB 153 was redistributed due to trophic
      transfer. On average, 33% of the HxCB 153 was sorbed to ciliates over the course
      of the experiment. In the experiment with algae and bacteria, the HxCB 153
      concentrations were relatively stable over time. The largest fraction partitioned
      into bacteria (57%), whereas only 4% of the HxCB 153 sorbed to the algae. The
      uptake was 8-fold higher in ciliates than in algae, although the algal biomass
      was 10-fold higher. The results imply that trophic transfer may be a significant
      transport route of more hydrophobic organic contaminants (HOCs) in plankton
      communities. In transfer models, this pathway may be taken into consideration so
      that the transport rate of HOCs to higher trophic levels is not underestimated.

PMID- 11596745
TI  - Characterization of estrogenic compounds in water samples collected from United
      Kingdom estuaries.
AB  - This report describes the identification of important estrogenic compounds in
      surface and sediment pore-water samples collected from the Tyne and Tees
      estuaries (United Kingdom) through the application of toxicity identification
      evaluation (TIE) procedures. The Tyne and Tees estuaries represent estuaries that
      have been historically impacted by industrial activities and continue to receive
      treated domestic sewage and industrial effluent. In 1998, Dabholm Gut on the Tees
      received a mixture of treated and untreated effluent, while Howdon sewage
      treatment works (STW) discharged primary treated effluents. An estrogenically
      active water sample collected from Howdon STW on the Tyne was shown to contain
      17beta-estradiol, androsterone, and an unknown estrogenic compound(s). Most of
      the activity contained in a sample collected from the Dabholm Gut combined
      discharges on the Tees was also due to 17beta-estradiol with additional activity
      from nonylphenol and (tentatively) bis(2-ethylhexyl)phthalate. The only sediment
      pore-water sample to demonstrate estrogenic activity was collected from Dabholm
      Gut.

PMID- 11596746
TI  - Vertical distribution profiles of linear alkylbenzene sulfonates and their long
      chain intermediate degradation products in coastal marine sediments.
AB  - The variation with depth of the concentration of linear alkylbenzene sulfonates
      (LASs) and of the long-chain sulfophenyl carboxylic acids (SPCs) resulting from
      LAS biodegradation was determined in coastal sediments. We analyzed samples of
      sediment cores taken from three locations in a littoral zone subjected to the
      discharge of untreated urban effluents in the Bay of Cadiz in the southwestern
      part of the Iberian Peninsula. The vertical profile of LAS concentrations showed
      a sharp reduction with depth, whereas the concentration of long-chain SPCs (6-13
      carbon atoms) was greatest at 10 to 14 cm depth. At this depth, the conditions in
      the interstitial water are strictly anoxic (Eh = -380 mV). The partition
      coefficients between the solid phase of the sediment versus the interstitial
      water are very different for LAS and for its degradation intermediates. For LAS,
      the organic carbon-based partition coefficient values were between 2.4 x 10(3)
      and 6.6 x 10(5)L/kg for the C10 and C13 homologues, respectively; these values
      are similar to those obtained from laboratory tests for the sorption of LAS onto
      marine sediments. For the long-chain SPCs, the partition coefficients are several
      orders of magnitude less as a consequence of their lower hydrophobicity.

PMID- 11596747
TI  - Effect of petrochemical sludge concentrations of changes in mutagenic activity
      during soil bioremediation process.
AB  - The present study was performed to assess the effect of the petrochemical sludge
      application rate on the mutagenic activity (Ames test) of soil and the
      persistence of mutagenic activity during laboratory soil bioremediation process.
      Sludge-soil systems were prepared at four different sludge application rates
      (1.25, 2.5, 5, and 10% w/w). Unamended soil was used as a control. Immediately
      following sludge application, in the absence or presence of S9, a linear
      correlation between sludge application rates and mutagenicity was found but
      differed significantly (p < 0.05) from the control system only at higher
      application rates (5 and 10% w/w). The direct mutagenicity of all systems
      decreases during the bioremediation process, and after a year of treatment only
      the 10% system induced a mutagenic response that was significantly different from
      the control system. On the other hand, an initial increase of the indirect
      mutagenicity was observed at all application rates. The time required for
      observing this increase was inversely proportional to the initial sludge
      concentration. After a year of treatment, the indirect mutagenicity of all sludge
      amended soils was not significantly different but was significantly different
      from the unamended soils. The persistence of the direct mutagenic activity of the
      sludge-amended soils was related to the sludge concentration, whereas the
      indirect mutagenic persistence was related to the relationship between easily
      degradable hydrocarbons and polynuclear aromatic hydrocarbons concentration and
      independent from the initial application rate.

PMID- 11596748
TI  - Air-water partition constants for volatile methyl siloxanes.
AB  - Silicones are an important class of hydrophobic compounds in widespread use. To
      evaluate their fate in the environment, an accurate value of the air-water
      partition (Henry's law) constant is necessary, which, unfortunately, is lacking
      at present. A static head space and a newly developed dynamic vapor entry loop
      method were used to obtain the air-water partition constant for six volatile
      methyl siloxanes. Internally consistent data were obtained. The value of Henry's
      constant, as calculated from pure component vapor pressure and aqueous
      solubility, was 10- to 170-fold greater than the experimental values. A
      correction to the Henry's constant that involves the ratio of the thermodynamic
      activity coefficient for a methyl siloxane at infinite dilution to that at
      saturation solubility in the aqueous phase is proposed.

PMID- 11596749
TI  - The effect of 2,5,2',5'-tetrachlorobiphenyl on growth and death of the
      cyanobacterium Anabaena flos-aquae.
AB  - The effect of 2,5,2',5'-tetrachlorobiphenyl (TcBP) on cell death was investigated
      in the cyanobacterium Anabaena flos-aquae (Lyngb.) Breb grown in a P-limited,
      semicontinuous culture under N2-fixing conditions during a 17-d period. The TcBP
      was supplied daily to yield final concentrations of 1, 10, and 100 ppb (or
      ng/ml). At 1 and 10 ppb, the population size of live cells (sum of live
      vegetative cells and live heterocysts) was not different from that of the TcBP
      free controls (p > 0.1, t test) and remained constant both in its absolute value
      (9.6 X 10(5) cells/ml) and as a percentage of the total population (98.6%).
      However, at 100 ppb, the population size of live cells declined significantly
      after the 11th day (8.2 x 10(5) cells/ml, or 96.6% of total population; p < 0.01,
      t test). The decrease in viable cells was mostly found in vegetative cells.
      Bioconcentration factor in the cell ([pg TcBP/g dry wt cells]/[pg TcBP/ml]) was
      1.23 x 10(5).

PMID- 11596750
TI  - Degradation of a stilbene-type fluorescent whitening agent with hypochlorite:
      identification of the degradation products by capillary electrophoresis.
AB  - The E,E-(4,4'-bis[2-sulfostyryl]biphenyl) (DSBP) is a fluorescent whitening agent
      widely used by the textile and detergent industries to whiten fabrics.
      Hypochlorite used to bleach fabrics oxidizes DSBP slowly at room temperature and
      in a higher rate at 60 degrees C. The ions of metals such as Fe, Cu, and Mn
      accelerate the process considerably. At ambient temperature, the oxidation
      results from cleavage of the stilbene bonds and involves the formation of various
      intermediates that evolve to end products. The intermediates form within minutes
      to hours and the end products within months. At 60 degrees C or in presence of
      the previously mentioned transition metals, intermediates form within minutes and
      the end products within days. The end products of the oxidation are 4
      sulfobenzaldehyde and 4,4'-bisaldehyde biphenyl; in the presence of excess of
      hypochlorite, however, the process yields their corresponding oxidized
      derivatives 4-sulfobenzoic acid and 4,4'-biphenyldicarboxylic acid. Despite the
      chlorinating ability of hypochlorite, the major degradation products formed
      contain no chlorine.

PMID- 11596751
TI  - Compositional and chiral profiles of weathered chlordane residues in soil.
AB  - The fate of chlordane and other persistent organic pollutants in the environment
      is of international concern. The behavior of persistent organic pollutants under
      both abiotic and biotic conditions must be determined for the comprehensive
      elucidation of their cycling through the biosphere. Standard analytical methods
      such as gas chromatography with electron capture detection are adequate for
      studies of cycling under abiotic conditions. Since two of the main components of
      technical chlordane, cis-chlordane and trans-chlordane, are optically active,
      chiral gas chromatography can be used to study the impact of biotic influences on
      chlordane's fate. We report here the use of chiral gas chromatography interfaced
      with ion trap mass spectrometry as part of an analytically rigorous method for
      the simultaneous determination of the compositional and chiral profiles of
      weathered soil residues of technical chlordane. Using the method described,
      several patterns in the long-term weathering of technical chlordane in soil are
      observed.

PMID- 11596753
TI  - Effect of varying pesticide exposure duration and concentration on the toxicity
      of carbaryl to two field-collected stream invertebrates, Calineuria californica
      (Plecoptera: Perlidae) and Cinygma sp (Ephemeroptera: Heptageniidae).
AB  - The effect of exposure duration on the toxicity of a forest insecticide
      (carbaryl) was assessed under environmentally realistic exposure regimes against
      two stream invertebrates indigenous to the United States Pacific Northwest,
      Calineuria californica (Plecoptera: Perlidae) and Cinygma sp. (Ephemeroptera:
      Heptageniidae). Laboratory bioassays were conducted to evaluate the relationship
      between pulsed exposures of 15, 30, and 60 min and toxicity for a range of
      chemical concentrations (10.2-1,730 microg/L). For Cinygma sp., the 50% lethal
      concentration (LC50) values were calculated as 848 microg/L (15 min), 220
      microg/L (30 min), and 165 microg/L (60 min). The C. californica consistently had
      lower mortality at a given concentration compared with Cinygma sp. Fifteen- and
      30-min exposures did not elicit 50% mortality with C. californica, and it had a
      60-min LC50 of 1,139 microg/L. Time to 50% mortality over 96 h after a 15-, 30-,
      or 60-min exposure, with the rest of the test period in freshwater (PLT50), was a
      function of exposure duration and concentration. Analysis of symptomology
      throughout the test period for C. californica gave evidence of recovery from the
      knockdown and moribund states, but this was not the case for Cinygma sp. The
      pulse duration resulting in 50% mortality was calculated as 43 min for Cinygma
      sp. exposed at 204 microg/L and 16 min at 408 microg/L. A three-dimensional
      probit plane model [Y = -10.86 + 4.83(ln C) + 3.0(ln T)], where Y is probit
      mortality, C is concentration in microg/L and T is time in hours, was used to
      explain the interaction between concentration (microg/L) and duration of exposure
      (hours) for Cinygma sp.

PMID- 11596752
TI  - A test system to evaluate the susceptibility of Oregon, USA, native stream
      invertebrataes to triclopyr and carbaryl.
AB  - The susceptibility of six indigenous macroinvertebrate species representative of
      U.S. Pacific Northwest streams (Ameletus sp., Brachycentrus americanus,
      Calineuria californica, Cinygma sp., Lepidostoma unicolor, Psychoglypha sp. early
      and late instar) to formulated triclopyr ester (herbicide) and carbaryl
      (insecticide) was determined using laboratory bioassays. Acute toxicity was
      expressed as the lethal concentration to 50% (LC50) and 1% (LC1) of the test
      population based on a 96-h exposure duration. Carbaryl was found to be 1,000
      times more toxic than triclopyr for all the organisms tested. The LCI values
      (7.5, 28.8, 9.0, 3.0, 9.5, 14.8, 33.8 microg/L, respectively, for carbaryl and
      1.8, 3.9, 4.0, 4.2, 29.0, 16.1 mg/L, respectively, for triclopyr) were used in
      the calculation of hazardous concentration to 5% of the stream macroinvertebrate
      community (HC5) based on the lower 95% confidence limit (HC5/95). The hazardous
      concentration (HC5/95) for triclopyr was 0.11 mg/L and for carbaryl ranged from
      0.43 to 0.66 microg/L, respectively. Triclopyr and carbaryl symptomology were
      analyzed for two organisms, C. californica and Cinygma sp. Carbaryl symptomology
      included knockdown and moribund states with severity and time of appearance being
      a function of dose. In triclopyr poisoning, death occurred suddenly with little
      or no symptomology. Time to 50% mortality (LT50) values were consistently higher
      for C. californica than for Cinygma sp. exposed to both chemicals at similar
      concentrations.

PMID- 11596754
TI  - Genetic diversity of the major histocompatibility complex of cotton rats
      (Sigmodon hispidus) inhabiting an oil refinery complex.
AB  - We examined genetic diversity of an immune-response gene within the major
      histocompatibility complex in cotton rats (Sigmodon hispidus) inhabiting an oil
      refinery complex. Genetic diversity of MHC-DQA exon-2 was examined within and
      among contaminated and noncontaminated reference grids. The level of gene
      diversity within contaminated grids (0.748) was lower than within reference grids
      (0.818), but the difference was not statistically significant (p > 0.5). Analysis
      of molecular variance, pairwise FST values, and hierarchical clustering failed to
      reveal population genetic structure related to contamination. Results of this
      study indicate either that the level of contaminant-induced selection is
      insignificant at this major histocompatibility complex (MHC) locus or that gene
      flow from surrounding areas has obliterated the effects of selection.

PMID- 11596755
TI  - Laboratory and field studies on the effect of molinate, clomazone, and
      thiobencarb on nontarget aquatic invertebrates.
AB  - The midge Chironomus tepperi was used in laboratory experiments to assess the
      relative toxicity of formulated molinate, clomazone, and thiobencarb, three
      herbicides used in Australian rice crops. Static bioassays were initiated with
      first-instar larvae at herbicide concentrations between 0.0625 and 2 times the
      anticipated field concentrations (AFCs) expected from the registered application
      rates. Adult emergence success, development time, and wing length were used as
      indices of the effect of each herbicide. Clomazone had no effect on any
      parameters at concentrations up to 0.288 mg/L (p > 0.05). Molinate significantly
      increased development time at concentrations equivalent to the AFC (3.6 mg/L) and
      above (p < 0.05). Thiobencarb reduced emergence success of adult C. tepperi at
      0.0625 times the AFC (0.1875 mg/L) as well as decreasing male adult size and
      increasing development time for males and females at 0.125 times the AFC (p <
      0.05). Nontarget effects of the herbicides on aquatic invertebrate communities
      were assessed in shallow experimental ponds using commercial application rates.
      One week after treatment, only thiobencarb had a significant effect, suppressing
      populations of chironomids, calanoids, and cyclopoids (p < 0.05). Four weeks
      later, all populations had recovered, equaling or exceeding control densities.

PMID- 11596756
TI  - Toxicity of atrazine to the estuarine phytoplankter Pavlova sp.
      (Prymnesiophyceae): increased sensitivity after long-term, low-level population
      exposure.
AB  - Phytoplankton are potentially more at risk to the adverse effects of herbicides
      than many other organisms in estuarine ecosystems. The focus of this study was to
      characterize the toxicity of a widely used herbicide, atrazine, to a single
      species of phytoplankton. The nanoplankter Pavlova sp. was grown under controlled
      laboratory conditions and was used to elucidate short-term, high-level population
      effects of atrazine. Secondly, a long-term, multigenerational population exposure
      was performed with a low level of atrazine followed by an additional short-term,
      high-level exposure on the same population with no recovery period. The 96-h
      growth rate of 50% effective concentration (EC50) for Pavlova sp. was 147
      [microg/L (95% CI = 116.4-178.7 microg/L). Long-term exposure at 20 [microg/L for
      four (batch culture) growth cycles (approximately 20 generations) had no
      significant effect on the growth rate of Pavlova sp. except during the fourth
      growth cycle. However, a subsequent short-term, high-level 96-h exposure
      inoculated from the long-term, low-level exposed population showed increased
      sensitivity to atrazine (96-h growth rate EC50 = 96.0 microg/L, 95% CI = 90.2
      103.7 microg/L). Multigenerational exposure to atrazine appeared to render
      phytoplankton significantly more sensitive (35%) to atrazine effects. Given the
      documented persistence of atrazine in surface waters, long-term exposure to low
      levels of atrazine without recovery may lead to shifts in species sensitivity and
      potential alterations in phytoplankton population dynamics.

PMID- 11596757
TI  - A comparison of the effect of new and established insecticides on nontarget
      invertebrates of winter wheat fields.
AB  - Six insecticides, a carbamate (pirimicarb), four pyrethroid/mixtures (tao
      fluvalinate, zeta-cypermethrin, deltamethrin, and pirimcarb+deltamethrin), and an
      organophosphate (dimethoate), registered for use within cereals, were field
      tested for toxicity to beneficial nontarget invertebrate groups important as food
      for farmland birds. Compared to the control and the other compounds, pirimicarb
      was the least toxic for most invertebrate groups examined. The pyrethroids and
      pyrethroid mixture significantly reduced numbers of many of the nontarget groups
      compared to the control and pirimicarb. Tao-fluvalinate was the least toxic
      pyrethroid tested when compared to the other compounds. Toxicity was further
      tested on larvae of graminivorous sawflies, an important chick- food group, using
      field-sprayed plants in laboratory and semifield trials. None of the pyrethroid
      and carbamate compounds and mixtures was as toxic as the organophosphate, but all
      were more toxic than the control. The semifield experiments provided a useful way
      of determining potential insecticide impact on this nontarget group where field
      populations are often too low for field trials to have statistically conclusive
      results.

PMID- 11596758
TI  - Arsenic biotransformation by the brown macroalga, Fucus serratus.
AB  - The brown alga Fucus serratus was maintained in aquaria with added arsenate (0,
      20, 50, and 100 microg As/L, four individuals per treatment) for up to 19 weeks.
      Biotransformation of arsenic by Fucus was monitored by high-performance liquid
      chromatography/inductively coupled plasma mass spectrometry and liquid
      chromatography/electrospray mass spectrometry analysis of aqueous extracts of
      algal frond tips removed periodically throughout the experiment. Major arsenic
      species monitored were arsenate, arsenite, methylarsonate, dimethylarsinate, and
      the four arsenosugars 1 to 4 found naturally in Fucus. Algae accumulated arsenate
      readily and transformed it into several arsenic compounds depending on the
      exposure concentration. At 100 microg As/L, the major metabolite was arsenite
      with smaller quantities of methylarsonate and dimethylarsinate, but only traces
      of arsenosugars were formed. In contrast, the 20-microg-As/L group accumulated
      only small quantities of arsenite and methylarsonate, while dimethylarsinate and
      arsenosugars were major arsenic metabolites. At 50 microg As/L exposure, algae
      had significant quantities of all arsenic metabolites monitored. Arsenate was
      toxic to the algae at 100 microg As/L but had no obvious detrimental effect at 20
      microg As/L. The data are consistent with a process of arsenate detoxification by
      reduction and alkylation; at higher exposures, however, the alkylation processes
      become saturated, leading to an accumulation of arsenite and subsequent toxicity.

PMID- 11596759
TI  - Polychlorinated biphenyl contamination and minisatellite DNA mutation rates of
      tree swallows.
AB  - The evidence that exposure to polychlorinated biphenyls (PCBs) leads to mutations
      is equivocal and controversial. Using multilocus DNA fingerprinting, we compared
      the mutation rate of tree swallows (Tachycineta bicolor) nesting at sites with
      high and low levels of contamination with PCBs. The upper Hudson River, USA, is
      highly contaminated with PCBs as a result of releases from two capacitor
      manufacturing plants in Hudson Falls and Fort Edward, New York, USA. Tree
      swallows nesting nearby have some of the highest known concentrations of PCBs in
      their tissues of any contemporary bird population (up to 114,000 ng PCB/g
      tissue). We found no difference in mutation rates between sites in New York with
      high PCB contamination and reference sites in Wisconsin, USA, and Ontario and
      Alberta, Canada, with known or presumably low levels of contamination. Thus, the
      mechanism behind altered reproductive behavior of tree swallows along the upper
      Hudson River is most likely physiological impairment, such as endocrine
      disruption, rather than mutation.

PMID- 11596760
TI  - Assessment of the estrogenicity and toxicity of a domestic wastewater effluent
      flowing through a constructed wetland system using biomarkers in male fathead
      minnows (Pimephales promelas rafinesque, 1820).
AB  - The toxicity and estrogenicity of a final treated municipal effluent was examined
      while flowing through a constructed wetland in north-central Texas, USA. Fish
      data were collected, and a baseline wetland characterization was performed to
      assess wetland treatment potential for these effluent properties. Vitellogenin
      (VTG), gonadosomatic index (GSI), hepatosomatic index (HSI), and secondary sexual
      characteristics were biomarkers used in fish models to assess aqueous
      estrogenicity. Biological indicators used to assess overall fish health included
      hematocrit and condition factor. Estrogenic nature of final sewage treatment
      works effluent was screened, concurrent with a three-week fish exposure, via gas
      chromatography/mass spectrometry for target estrogenic compounds, including
      17beta-estradiol, ethynylestradiol, bisphenol A, nonylphenolic compounds,
      phthalates, and DDT. The VTG in Pimephales promelas was measured after exposure
      at four sites in a treatment wetland and was significantly elevated (p < 0.0001)
      in fish exposed at the inflow site. The GSIs were significantly less (alpha =
      0.001) at the inflow site. At wetland sites closest to the inflow, secondary
      sexual characteristics, tubercle numbers, and fatpad thickness were less (alpha =
      0.0001) than in laboratory controls. The HSIs and density of male breeding
      stripes were not significantly different from those of laboratory controls.
      However, elevated HSIs were found at the inflow site. Hematocrit and condition
      factors were both less (alpha = 0.001) in effluent-exposed fish at wetland sites
      closer to the inflow than in control fish or fish further downstream.

PMID- 11596761
TI  - An evaluation of methods for calculating mean sediment quality guideline
      quotients as indicators of contamination and acute toxicity to amphipods by
      chemical mixtures.
AB  - Mean sediment quality guideline quotients (mean SQGQs) were developed to
      represent the presence of chemical mixtures in sediments and are derived by
      normalizing a suite of chemicals to their respective numerical sediment quality
      guidelines (SQGs). Mean SQGQs incorporate the number of SQGs exceeded and the
      degree to which they are exceeded and are used for comparison with observed
      biological effects in the laboratory or field. The current research makes it
      clear, however, that the number and type of SQGs used in the derivation of these
      mean quotients can influence the ability of mean SQGQ values to correctly predict
      acute toxicity to marine amphipods in laboratory toxicity tests. To determine the
      optimal predictive ability of mean SQGQs, a total of 18 different chemical
      combinations were developed and compared. The ability of each set of mean SQGQs
      to correctly predict the presence and absence of acute toxicity to amphipods was
      determined using three independent databases (n = 605, 2753, 226). Calculated
      mean SQGQ values for all chemical combinations ranged from 0.002 to 100. The mean
      SQGQ that was most predictive of acute toxicity to amphipods is calculated as
      SQGQ1 = ((sigma ([cadmium]/4.21 )([copper]/270)([lead]/
      12.18)([silver]/1.77)([zinc]/ 410)([total chlordane]/6)([dieldrin]/8)([total
      PAHoc]/1,800)([total PCB]/400))/9). Both the incidence and magnitude of acute
      toxicity to amphipods increased with increasing SQGQI values. To provide better
      comparability between regions and national surveys, SQGQ1 is recommended to serve
      as the standard method for combination of chemicals and respective SQGs when
      calculating mean SQGQs.

PMID- 11596762
TI  - Pollution-induced community tolerance and functional redundancy in a decomposer
      food web in metal-stressed soil.
AB  - Pollution may lead to the development of pollution-induced community tolerance
      (PICT) in a stressed community. We studied the presence of PICT in soil food webs
      using soil microcosms. Soil microcosms containing soil invertebrates and microbes
      were collected from polluted and unpolluted areas and exposed to a range of soil
      zinc concentrations. A pine seedling was planted in each microcosm to measure the
      effects of the origin of the community and Zn pollution on above-ground plant
      production. The effects of the treatments on nutrient content in the soil were
      also measured. The diversity of soil microarthropods and the soil's mineral
      nutrient content were low at the Zn-polluted site. We did not observe an
      increasing Zn tolerance among the soil organisms in the polluted soil. However,
      low population growth rates of soil invertebrates from the polluted site may
      indicate the deleterious effects on fitness of long-lasting pollution. In the
      soil from the nonpolluted site, Zn additions caused changes in the invertebrate
      food web structure. These changes were explained by the good physiological
      condition of the animals and their insensitivity to Zn. The fact that the food
      web structure in soil from the polluted site did not change can be used as a
      rough indicator of PICT. Structural stability is presumed by the lack of Zn
      sensitive species at this site and the inability of populations to acclimate by
      altering their growth or reproduction patterns in response to changing soil
      conditions. Although microbial-based soil decomposer systems may have a high
      functional redundancy, our results indicate that metal stress at the polluted
      site exceeds the tolerance limits of the system. As a consequence, ecosystem
      function at this site is endangered. This study also shows that the evolution of
      metal tolerance by soil decomposer organisms may not be a common reaction to soil
      pollution, although changes of population and community structure indicated
      severe metal stress on organisms.

PMID- 11596763
TI  - Toxicokinetics of waterborne bisphenol A in landlocked salmon (Salmo salar m.
      sebago) eggs at various temperatures.
AB  - Eye-pigmented eggs of landlocked salmon were exposed to waterborne [14C]-labeled
      bisphenol A at four temperatures (2, 6, 8, and 12 degrees C). Both in
      accumulation and depuration experiments, the eggs were exposed to a bisphenol A
      concentration of 1 microg/L for 196 h. In the depuration experiment, the exposed
      eggs were placed into clean water for 96 h. At each sampling time, the eggs were
      dissected into three parts (eggshell, embryo, and yolk sac), and all of these
      parts were weighed and analyzed separately in a liquid scintillation counter. The
      results show that waterborne bisphenol A accumulates in developing salmon eggs.
      Accumulation of bisphenol A showed a clear trend both in whole eggs and in
      dissected parts: the higher the temperature, the higher the uptake rate constant
      and the concentration of bisphenol A. Steady state was reached only in the
      embryos at the lowest temperature; in other cases, accumulation was linear.
      Depuration was significant only in the embryos at 2 and 6 degrees C. As the
      accumulation and the depuration results show, the elimination of bisphenol A was
      evidently more significant at lower temperatures.

PMID- 11596764
TI  - Effects of water hardness and dissolved organic material on bioavailability of
      selected organic chemicals.
AB  - The influence of water hardness and dissolved organic matter (DOM) on
      bioavailability of organic chemicals to Daphnia magna was studied by using
      benzo[a]pyrene (BaP), pyrene, atrazine, and 3,3',4,4'-tetrachlorobiphenyl (TCB)
      as model compounds. Two types of DOM were used, namely Lake Kontiolampi, Joensuu,
      Finland water (KL) and Nordic reference fulvic acid (NoFA) dissolved in
      artificial freshwater. Binding of the four contaminants by KL DOM decreased with
      increasing water hardness. Furthermore, increasing hardness reduced the binding
      of BaP and pyrene to NoFA. The binding of atrazine and TCB by NoFA was low and
      was not significantly affected by water hardness. In the DOM-free samples, the
      bioconcentration of the four contaminants in D. magna usually was not affected by
      water hardness. In the presence of DOM, the bioconcentration factors (BCFs) were
      lower (except for atrazine) than in the DOM-free controls. In the presence of
      both types of DOM, increasing water hardness resulted in higher BCFs for BaP. The
      bioconcentration of pyrene and TCB increased with increasing water hardness in
      the presence of KL DOM. In conclusion, the effects of DOM and water hardness on
      bioavailability of hydrophobic chemicals depend on the type of chemical and on
      the properties of DOM.

PMID- 11596765
TI  - Sediment geochemical controls on CD, CR, and ZN assmilation by the clam Ruditapes
      philippinarum.
AB  - Several important sediment geochemical factors (particle size, contact time,
      artificial sediment composition, acid volatile sulfide, and pure inorganic
      particles coated or uncoated with humic acid) were examined for their influences
      on the assimilation of Cd, Cr, and Zn in the marine clam Ruditapes philippinarum.
      Metal desorption and phase speciation were concurrently measured for these
      particles. Differences in particle size did not significantly affect metal
      assimilation. Increasing contact time with sediments decreased assimilation by
      the clams of Cr and Zn, but not of Cd. A significant positive relationship was
      found between the metal assimilation efficiency (AE) and the metal partitioning
      in the exchangeable fraction of sediments for Cd and Zn. The assimilation of
      metals was negatively dependent on the metal distribution in the reducible (Fe
      oxide) fraction, indicating that Fe oxide reduced metal bioavailability to the
      clams. Metal AEs measured with artificially prepared sediments were comparable to
      those measured with natural sediments. The AEs were significantly higher in
      artificial sediment without Fe oxide. Humic acid coating appeared to have no
      major and consistent influence on metal assimilation by the clams. The AEs
      measured for pure inorganic particles were much higher than those measured for
      sediments or artificially prepared sediments, except for the Fe oxide particles,
      indicating that digestion may behave differently for pure particles. Metals bound
      to artificially synthesized acid volatile sulfide were much less bioavailable to
      the clams. The AEs were as low as 4% for Cd and 7% for Zn, whereas the AE for Cr
      was somewhat similar to those measured for other types of particles. When all
      particle types (natural sediments, artificial sediment, and pure particles) were
      considered, a significant relationship was found between Cd AE and its desorption
      in seawater. This study has demonstrated that several geochemical fractions of
      the sediments, particularly the exchangeable, Fe oxide, and sulfide fractions,
      are important in determining metal bioavailability from sediments to clams.

PMID- 11596766
TI  - Reproductive toxicity in mink (Mustela vison) chronically exposed to
      environmentally relevant polychlorinated biphenyl concentrations.
AB  - Female mink were exposed to a technical polychlorinated biphenyl (PCB)
      preparation (Clophen A50 [A50]; 0.1 or 0.3 mg/animal/d), one fraction of A50
      containing the non- and mono-ortho-chlorinated congeners (0-1-ortho
      chlorobiphenyls [CBs]), another fraction of A50 containing the congeners with two
      to four ortho-chlorines (2-4-ortho-CBs), or an organic extract from Baltic gray
      seal blubber. The animals were exposed for 18 months, including two reproduction
      seasons. Among the animals given the highest dose of A50, the whelping frequency
      was reduced in the second reproductive season, and all kits died within 24 h of
      birth. Reproduction was also impaired by the lower dose of A50. Daily exposure to
      the 0-1-ortho-CBs separated from 0.3 mg A50 severely reduced kit survival.
      Reproduction was not significantly impaired by daily exposure to the 2-4-ortho
      CBs separated from 0.3 mg A50 or by exposure to the blubber extract. We conclude
      that the reproductive toxicity in chronically PCB-exposed mink is caused by the
      aryl hydrocarbon (Ah) receptor agonists. The lowest-observed-effect level for
      reproductive impairment was 2.4 ng 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      equivalents (TEQs) per kilogram body weight and day (22 pg TEQs/g feed).
      Ethoxyresorufin-O-dealkylase (EROD) was strongly induced by the 0-1-ortho-CBs and
      pentoxyresorufin-O-dealkylase by the 2-4-ortho-CBs. High EROD activity was
      correlated with low kit production, and consequently EROD may serve as a marker
      for reproductive toxicity by Ah receptor agonists in mink.

PMID- 11596767
TI  - Juvenile amphibians do not avoid potentially lethal levels of urea on soil
      substrate.
AB  - We examined the effects of a forest fertilizer (urea) on newly metamorphosed
      terrestrial amphibians (Western toads, Bufo boreas; Cascades frogs, Rana
      cascadae; long-toed salamanders, Ambystoma macrodactylum; and roughskin newts,
      Taricha granulosa). We examined avoidance behavior of Western toads and Cascades
      frogs on both paper towel and soil substrates dosed with urea (control and 100 kg
      N/ha and an additional treatment of 50 kg N/ha for Western toads on soil
      substrate) and avoidance behavior of long-toed salamanders on soil substrate
      dosed with urea. We further examined the survival and feeding behavior of all
      four species exposed to urea on soil substrate (100 kg N/ha) for 5 d. Juvenile
      Western toads and Cascades frogs avoided paper towels dosed with urea but did not
      avoid urea-dosed soil substrate. However, Western toads and Cascades frogs both
      suffered significant mortality when exposed to urea on a soil substrate for 5 d.
      Furthermore, after adjusting for weight, we found that urea-exposed juvenile
      Western toads and Cascades frogs consumed significantly fewer prey items
      (crickets) compared with nonexposed control animals. Long-toed salamanders did
      not discriminate against soil substrate dosed with urea, and neither long-toed
      salamanders nor roughskin newts died or reduced prey consumption as a result of
      urea exposure. Juvenile amphibians may not be able to detect and avoid harmful
      levels of urea fertilizer on a natural substrate. Furthermore, anthropogenic
      stressors such as urea fertilizer can significantly reduce the survival and prey
      consumption of juvenile amphibians. These effects are important to consider in
      light of possible threats to the conservation status of many amphibian species.

PMID- 11596768
TI  - Resistance to copper toxicity in populations of the earthworms Lumbricus rubellus
      and Dendrodrilus rubidus from contaminated mine wastes.
AB  - Two arsenic and heavy metal-contaminated mine spoil sites, at Carrock Fell,
      Cumbria, United Kingdom, and Devon Great Consols Mine, Devon, United Kingdom,
      have been found to support populations of the earthworms Lumbricus rubellus
      Hoffmeister and Dendrodrilus rubidus (Savigny). Lumbricus rubellus and D. rubidus
      collected from the Devon site and an uncontaminated site were kept for 28 d in
      uncontaminated soil and in soil containing 750 mg/kg CuCl2, the state of the
      specimens being recorded using a semiquantitative assessment of earthworm health
      (condition index). The condition index remained high for all specimens except
      those of L. rubellus and D. rubidus from uncontaminated sites, which displayed
      100% mortality. Bioavailability of Cu in the soils from one uncontaminated and
      two contaminated sites and in the uncontaminated soil treated with CuCl2 was
      determined using sequential extraction. Soils from Devon Great Consols had the
      greatest availability of Cu, Carrock Fell the lowest. Total tissue Cu for L.
      rubellus and D. rubidus from the contaminated sites did not change significantly
      for each species during the experiment. Total tissue concentrations of Cu for L.
      rubellus and D. rubidus from uncontaminated sites increased significantly during
      the first 7 d, after which mortality was 90%, making it impossible to continue
      the analysis.

PMID- 11596769
TI  - Naturalized salmonid populations occur in the presence of elevated trace element
      concentrations and temperatures in the Firehole River, Yellowstone National Park,
      Wyoming, USA.
AB  - We investigated the effects of geothermally influenced waters on the distribution
      of rainbow trout, Oncorhynchus mykiss, and brown trout, Salmo trutta, in the
      Firehole River and its tributaries in Yellowstone National Park (WY, USA) from
      June 1997 to June 1998. Geothermal features in the Firehole River basin elevate
      mineral content and temperature in portions of the river and its tributaries. We
      found concentrations of boron and arsenic to be elevated in geothermally
      influenced areas compared with upstream sites. Boron concentrations occasionally
      exceeded 1,000 microg/L, a proposed limit for the protection of aquatic
      organisms. Arsenic concentrations occasionally exceeded 190 microg/L, the chronic
      ambient water quality criterion. Temperatures in geothermally influenced sites
      ranged up to 30 degrees C and were consistently 5 to 10 degrees C higher than
      upstream sites unaffected by geothermal inputs. Rainbow trout occurred at sites
      with elevated concentrations of boron, arsenic, and other trace elements and
      elevated water temperatures. Rainbow trout inhabited and spawned at sites with
      the most elevated trace element concentrations and temperatures; however, brown
      trout were absent from these sites. Water temperature may be the major factor
      determining brown trout distributions, but we cannot exclude the possibility that
      brown trout are more sensitive than rainbow trout to boron, arsenic, or other
      trace elements. Further investigations are needed to determine species-specific
      tolerances of boron, arsenic, and other trace elements among salmonids.

PMID- 11596770
TI  - Bioassay of cadmium using a DNA microarray: genome-wide expression patterns of
      Saccharomyces cerevisiae response to cadmium.
AB  - DNA microarray technology enables genome-wide detection of cell response at the
      transcriptional level. We are planning to make bioassay systems that can detect
      environmental chemicals to screen for potential bioreactive agents. To develop a
      DNA microarray for our purposes, the changes in gene expression underlying the
      yeast stress response to cadmium were analyzed by a microarray of total mRNA.
      Cadmium is a potent cell poison known to cause oxidative stress by changing
      intracellular glutathione levels. We report here that not only the glutathione
      synthesis gene (GSH1) but also almost all transcripts of the enzymes involved in
      the sulfur amino acid metabolism, especially MET14 and MET17, were greatly
      induced after exposure to cadmium. While several common stress-responsive genes,
      such as HSP26, GRE1, HSP12, and DDR48, were up-regulated more than almost
      fourfold by cadmium, there were also 42 other genes up-regulated more than
      fourfold. Based on these results, we concluded that DNA microarrays are very
      useful instruments for creating new bioassay systems and finding genetic
      promoters of stress indicators.

PMID- 11596771
TI  - Joint action of chemicals in algal toxicity tests: influence of response level
      and dose-response regression model.
AB  - The joint toxicity of nonylamine and decylamine and of atrazine and decylamine
      was evaluated in assays with the green alga Selenastrum capricornutum based on an
      isobologram method. In this method, curves of constant response, isoboles, are
      plotted versus concentrations of two toxicants. The response parameter was growth
      rate based on biomass, and several response levels were used. Dose-response
      curves were developed for dilution series using fixed ratios between
      concentrations in toxic units of the compounds. Probit and Weibull dose-response
      curves were then determined by nonlinear regression. A model for isoboles for
      partially similar action was used when applicable. The no-effect concentration
      (NEC or EC0) was estimated based on a newly proposed model containing median
      effective concentration (EC50) and EC0 as explicit variables. Results show that
      nonylamine and decylamine are nearly concentration additive at EC50 and EC10
      (similarity parameter lambda = 0.70-0.76) and to a lesser extent at EC0. By
      contrast, the mixtures of atrazine and decylamine show antagonism in that
      atrazine acts as an antidote to decylamine. The shapes of these isoboles are
      independent of response level. The EC50 values (mg/L) for chemicals acting singly
      were 0.090 (nonylamine), 0.039 to 0.044 (decylamine), and 0.225 (atrazine). In
      order to determine NEC effectively, the level of inhibition must be fairly low,
      with observed growth rates between 0.6 and 1.0 times the average growth rate of
      the controls.

PMID- 11596772
TI  - Altered distribution of lipid-soluble antioxidant vitamins in juvenile sturgeon
      exposed to waterborne ethynylestradiol.
AB  - Studies in mammals have shown that exposure to estrogenic compounds can affect
      lipid metabolism and plasma concentrations of lipid-soluble vitamins. However,
      the potential for estrogenic contaminants to induce these effects in fish has not
      yet been examined. The ability of the estrogen analog ethynylestradiol (EE2) to
      alter concentrations of the lipid-soluble vitamins A and E in plasma, liver, and
      kidney was investigated in juvenile lake sturgeon (430 +/- 20 g). The EE2 was
      delivered to the sturgeon in the tank water at nominal concentrations of 0
      (control), 15, 60, or 125 ng EE2/L for a period of 25 d. Concentrations of the
      egg yolk precursor, vitellogenin, increased dose dependently in plasma. Plasma
      vitamin E (tocopherol), A1 (retinol), and A2 (dehydroretinol) were elevated by
      the two highest EE2 treatments compared with the controls. Esterified storage
      forms of vitamin A were marginally lower in the livers of fish from the highest
      EE2 dose group, but vitamin E levels in the liver were not significantly
      affected. Concentrations of vitamin E and vitamin A were significantly depleted
      in the kidney of fish from the two highest EE2 dose groups. Total lipid content
      was elevated in the gonad of fish treated with the highest dose of EE2 compared
      with the controls. Altered lipid and vitamin distribution may be induced by
      estrogen to facilitate gonadal maturation in sturgeon. Results from these studies
      indicate that an examination of the implications for vitamin depletion by
      estrogenic contaminants in juvenile fish is warranted.

PMID- 11596773
TI  - Disposition and depuration of lindane (gamma-HCH) and polychlorinated biphenyl
      110 (2,3,3'4'6-pentachlorobiphenyl) in cod (Gadus morhua) and bullrout
      (Myoxocephalus scorpius) after single oral exposures.
AB  - The disposition and depuration of lindane (gamma-hexachlorocyclohexane [HCH]) and
      polychlorinated biphenyl (PCB)-110 (2,3,3',4',6-pentachlorobiphenyl), orally
      administered to cod (Gadus morhua) and bullrout (Myoxocephalus scorpius), were
      investigated using whole-body autoradiography, liquid scintillation counting, and
      gas chromatography with electron-capture detection. Both gamma-HCH and PCB-110
      were distributed mainly to lipid-rich organs after absorption from the
      gastrointestinal tract of cod and bullrout. Compared to bullrout liver, the cod
      liver contained higher concentrations of both compounds, reflecting the
      distribution of fat in the two species. In both species, the depuration time for
      gamma-HCH was shorter than for PCB-110. Both substances were excreted via bile
      and urine, largely as water-soluble metabolites. The water-soluble bile
      metabolites, together with PCB-110 metabolites associated to endogenous
      macromolecules, strongly indicate that this compound is metabolized in both
      species.

PMID- 11596774
TI  - Biotic ligand model of the acute toxicity of metals. 1. Technical basis.
AB  - The biotic ligand model (BLM) of acute metal toxicity to aquatic organisms is
      based on the idea that mortality occurs when the metal-biotic ligand complex
      reaches a critical concentration. For fish, the biotic ligand is either known or
      suspected to be the sodium or calcium channel proteins in the gill surface that
      regulate the ionic composition of the blood. For other organisms, it is
      hypothesized that a biotic ligand exists and that mortality can be modeled in a
      similar way. The biotic ligand interacts with the metal cations in solution. The
      amount of metal that binds is determined by a competition for metal ions between
      the biotic ligand and the other aqueous ligands, particularly dissolved organic
      matter (DOM), and the competition for the biotic ligand between the toxic metal
      ion and the other metal cations in solution, for example, calcium. The model is a
      generalization of the free ion activity model that relates toxicity to the
      concentration of the divalent metal cation. The difference is the presence of
      competitive binding at the biotic ligand, which models the protective effects of
      other metal cations, and the direct influence of pH. The model is implemented
      using the Windermere humic aqueous model (WHAM) model of metal-DOM complexation.
      It is applied to copper and silver using gill complexation constants reported by
      R. Playle and coworkers. Initial application is made to the fathead minnow data
      set reported by R. Erickson and a water effects ratio data set by J. Diamond. The
      use of the BLM for determining total maximum daily loadings (TMDLs) and for
      regional risk assessments is discussed within a probabilistic framework. At first
      glance, it appears that a large amount of data are required for a successful
      application. However, the use of lognormal probability distributions reduces the
      required data to a manageable amount.

PMID- 11596775
TI  - Biotic ligand model of the acute toxicity of metals. 2. Application to acute
      copper toxicity in freshwater fish and Daphnia.
AB  - The biotic ligand model (BLM) was developed to explain and predict the effects of
      water chemistry on the acute toxicity of metals to aquatic organisms. The biotic
      ligand is defined as a specific receptor within an organism where metal
      complexation leads to acute toxicity. The BLM is designed to predict metal
      interactions at the biotic ligand within the context of aqueous metal speciation
      and competitive binding of protective cations such as calcium. Toxicity is
      defined as accumulation of metal at the biotic ligand at or above a critical
      threshold concentration. This modeling framework provides mechanistic
      explanations for the observed effects of aqueous ligands, such as natural organic
      matter, and water hardness on metal toxicity. In this paper, the development of a
      copper version of the BLM is described. The calibrated model is then used to
      calculate LC50 (the lethal concentration for 50% of test organisms) and is
      evaluated by comparison with published toxicity data sets for freshwater fish
      (fathead minnow, Pimephales promelas) and Daphnia.

PMID- 11596776
TI  - Update on recent progress in drug treatment for acute ischemic stroke.

PMID- 11596777
TI  - Disorders of emotional behaviour.
AB  - After having stressed the distinction between general adaptive systems and
      specific functional systems, the author argues that emotions constitute a general
      adaptive system distinct from, but interacting with, the cognitive system,
      considered as the other (more evolved) adaptive system. The main characteristics
      of the emotional system are its componential nature and its hierarchical
      organization. These basic features of the emotional system, as well as the brain
      structures subserving the different components of emotions must, therefore, be
      taken into account in the neuropsychological study of emotional disorders. The
      main components of emotions considered in this educational review are: the
      evaluation of emotional situations; the emotional response with its expressive
      motor and autonomic components and the inhibition of socially unacceptable
      spontaneous emotional responses. The main levels identified in the hierarchical
      structure of emotions are: a level of automatic, spontaneous functioning and a
      level of conceptual processing of emotional information and of controlled
      selection of the most appropriate response. The brain structures identified as
      critically involved in these different components and levels of emotions are: the
      amygdala, considered as the structure where the external stimuli are appraised in
      terms of their emotional significance; the insular cortex and the hypothalamus,
      crucially involved in the generation of the autonomic components of emotions; the
      ventral striatum, which subserves the execution of stereotyped emotional action
      patterns and the ventro-medial frontal cortex, playing a critical role in
      functions of control and inhibition of socially unacceptable emotional responses.
      The different emotional involvement of the right and left hemispheres in
      different aspects and levels of emotional processing is also shortly discussed
      and the quality of emotional disturbances resulting from injury to these brain
      structures is briefly considered.

PMID- 11596778
TI  - Presentation of striatal hyperintensity on T1-weighted MRI in patients with
      hemiballism-hemichorea caused by non-ketotic hyperglycemia: report of seven new
      cases and a review of literature.
AB  - Recent studies have shown unique clinicoradiologic characteristics in patients
      with hemiballism-hemichorea (HB-HC) caused by non-ketotic hyperglycemia; however,
      there is still a limited number of patients being reported. We report 7 patients
      (3 males and 4 females) with this type of dyskinesia, whose ages ranged from 60
      to 84 years. Brain CT of these patients showed hyperdensity in the contralateral
      striatum, corresponding with MRI studies that showed an increased signal
      intensity on T1-weighted images and a decreased signal on T2-weighted images.
      After metabolic control had been achieved, the hyperkinetic state of these
      patients abruptly ceased. Follow-up neuroimaging studies in 2 patients
      documentied complete resolution of the striatal hyperintensity on brain CT and
      MRI after 3 months and 6 months, respectively. A review of patients with HB-HC
      caused by non-ketotic hyperglycemia reported formerly and in the present study
      shows that the dyskinesia tends to occur in aged diabetic patients. The age of
      patients with dyskinesia secondary to cerebral infarction is generelly much
      lower. We also found that 86% (30 out of 35 cases) patients reported with HB-HC
      caused by non-ketotic hyperglycemia were Asians. The prognosis of the dyskinesia
      was excellent, and the radiological abnormalities are completely reversible.

PMID- 11596779
TI  - Evaluation of the roles of the Leiden V mutation and ACE I/D polymorphism in
      subtypes of ischaemic stroke.
AB  - OBJECTIVE: The Leiden V mutation, which causes activated protein C resistance and
      thrombophilia, has been found to be a risk factor for venous thrombosis. The
      angiotensin converting enzyme (ACE) D allele indirectly exerts an unfavourable
      effect on the vasoregulatory system. In this study, the frequency of these
      mutations was analysed in different subtypes of ischaemic stroke. METHOD AND
      MATERIAL: According to the clinical and radiological features 664 Hungarian
      patients who had suffered acute ischaemic stroke were divided into 3 subtypes:
      small and large vessel infarcts and a mixed type. In all 664 patients, the Leiden
      V mutation and ACE I/D polymorphism were examined by means of the PCR technique.
      The frequencies of the different genotypes for the Leiden V mutation and ACE I/D
      polymorphism in the 3 subgroups of stroke were compared with 199 stroke-free
      control subjects whose MRI findings were normal. RESULTS: No significant
      associations were found between the overall group of cerebral infarctions and the
      Leiden V, ACE I/D and ACE D/D genotypes. The ACE D/D genotype was significantly
      more common in the patients with small deep infarcts (40.3%; p < 0.0005; OR 2.31,
      95% CI 1.49-3.57) than in the control group (22.6%). The Leiden V mutation was
      significantly more common in patients with large infarcts (13.6%; p < 0.025; OR
      2.25, CI 1.16-4.34) than in the stroke-free control subjects (6.5%). CONCLUSIONS:
      The ACE D/D genotype possibly contributes to the occurrence of small-vessel
      infarcts rather than large vessel infarcts. The Leiden V mutation might
      predispose to large brain infarcts. Neither the Leiden V factor nor the ACE D/D
      genotype has been proved to be a risk factor for ischaemic stroke as a whole.

PMID- 11596780
TI  - Prevalence of epilepsy in northeast Madrid.
AB  - During a period of 42 months, we studied the prevalence of epilepsy in a specific
      health district, composing by four towns with 98,405 inhabitants older than 10
      years. This has been accomplished by a two-phase cross-sectional study. The
      prevalence rate observed was 4.12/1000 inhabitants for all types of epilepsy. No
      significant differences were found between the sexes. Sixty-three per cent of
      affected individuals had partial seizures, with a confirmed cause in 45%. Fifty
      five patients with single unprovoked seizures, were also identified but not
      included in the prevalence rate.

PMID- 11596781
TI  - Asymptomatic cerebral embolic signals in patients with acute cerebral ischaemia
      and severe aortic arch atherosclerosis.
AB  - Severe aortic arch atheroma (AAA) is a strong risk factor for ischaemic stroke,
      but it is unclear whether AAA is a source of cerebral emboli or simply a marker
      of cerebral atherosclerosis. The purpose of this study was to find out the
      prevalence of asymptomatic cerebral embolic signals (ES) in patients with acute
      cerebral ischaemia, AAA and no other potential source of cerebral embolism. Forty
      patients with anterior circulation ischaemic stroke or transient ischaemic attack
      (TIA) were prospectively studied using transesophageal echocardiography (TEE) and
      transcranial Doppler (TCD) scanning within seven days of symptom onset. Patients
      with a cardiac source of embolism or carotid stenosis > 50% were excluded. ES
      were detected in 14.3% (2/14) of patients with AAA > or = 4 mm and in no patients
      with AAA < 4 mm or no AAA (p=0.14). The findings suggest that ES may be
      associated with severe AAA but their prevalence is low in this setting.

PMID- 11596782
TI  - Pure motor chronic inflammatory demyelinating polyneuropathy.
AB  - We describe four patients affected by chronic inflammatory demyelinating
      polyneuropathy (CIDP) in a pure motor form. Selective involvement of motor fibers
      was suggested by the absence of sensory symptoms, normal sensation at
      neurological examination and normal findings on electrophysiological testing of
      sensory fibres and sural nerve biopsy. The onset of the disease occurred at a
      young age (3-29 years) and the clinical course was relapsing-remitting. Over a
      follow-up period of 1.5-14 years, periodical clinical and electrophysiological
      examinations showed that selective involvement of motor fibers remained a
      constant feature. Electromyography and nerve conduction studies continued to show
      a purely demyelinating neuropathy without signs of axonal impairment. All
      patients were steroid-unresponsive, whereas they considerably improved after
      being treated with immunoglobulins. Two patients were treated with interferon
      alpha and showed a good response. In conclusion, the occurrence in our four
      patients of pure motor involvement over a long period of time during which
      several relapses occurred, suggests that pure motor CIDP may represent the result
      of a specific immunological process rather than of a random distribution of
      inflammation throughout peripheral nerves.

PMID- 11596783
TI  - Retrospective study of a large population of patients affected with mitochondrial
      disorders: clinical, morphological and molecular genetic evaluation.
AB  - Mitochondrial disorders are human genetic diseases with extremely variable
      clinical and genetic features. To better define them, we made a genotype
      phenotype correlation in a series of 207 affected patients, and we examined most
      of them with six laboratory examinations (serum CK and basal lactate levels, EMG,
      cardiac and EEG studies, neuroradiology). We found that, depending on the genetic
      abnormality, hyperckemia occurs most often with either chronic progressive
      external ophthalmoplegia (CPEO) and ptosis or with limb weakness. Myopathic EMGs
      are more common than limb weakness, except in patients with A8344G mutations.
      Peripheral neuropathy, when present, is always axonal. About 80% of patients with
      A3243G and A8344G mutations have high basal lactate levels, whereas pure CPEO is
      never associated with increased lactate levels. Cardiac abnormalities mostly
      consist of conduction defects. Abnormalities on CT or MRI of the brain are
      relatively common in A3243G mutations independently of the clinical phenotype.
      Patients with multiple mtDNA deletions are somehow "protected" against the
      development of abnormalities with any of the tests. We conclude that, despite the
      phenotypic heterogeneity of mitochondrial disorders, correlation of clinical
      features and laboratory findings may give the clinician important clues to the
      genetic defect, allowing earlier diagnosis and counselling.

PMID- 11596784
TI  - Improved interobserver agreement for visual detection of active T2 lesions on
      serial MR scans in multiple sclerosis using image registration.
AB  - The aim of this study was to analyse the effect of image registration on
      interobserver agreement in the visual detection of active multiple sclerosis (MS)
      lesions from serial magnetic resonance (MR) scans. T2W spin-echo MR scans (3-mm
      slices) of 16 MS patients participating in a treatment trial were selected. For
      each patient, two pairs of scans were used: an original (i. e., non-registered)
      and a registered pair. For the original pair, baseline and month 6 were used, and
      for the registered pair month 3 and 9. For registration an automatic matching
      algorithm based on Mutual Information was used. Six observers identified active
      lesions on both original and registered scans. Kappa values were calculated to
      assess interobserver agreement. Reslicing caused a slight blurring of the images,
      but near perfect registration. The kappa value of 0.35 +/- 0.07 for new lesions
      on original images improved to 0.62 (+/- 0.06) by registration (p = 0.004). For
      enlarging lesions on original images it was extremely poor (kappa 0.11 +/- 0.05),
      and did not benefit much by registration (kappa 0.20 +/- 0.11). Thus, image
      registration improved interobserver agreement for visual detection of new
      lesions. For enlarging lesions, registration improved agreement but still not to
      a satisfactory level.

PMID- 11596785
TI  - The range of chronic demyelinating neuropathy of infancy: a clinico-pathological
      and genetic study of 15 unrelated cases.
AB  - The concept of Dejerine-Sottas disease, which corresponds to presumed recessive
      demyelinating neuropathies with onset in infancy, remains controversial. To learn
      more on the subject, we performed a clinico-pathological and molecular genetic
      study in 15 unrelated patients with the Dejerine-Sottas phenotype seen over a 16
      year period. There were 12 females and 3 males, born to asymptomatic parents.
      Study of the PMP22, P0 and Egr2 genes was performed in all cases and 14 underwent
      a nerve biopsy. First manifestations of neuropathy occurred before 3 years of age
      in all patients. An inherited disorder was suspected in 10 patients, because of
      their family history and/or disclosure of a molecular genetic defect in 4 of
      them. One patient had a recessively transmitted homozygous point mutation
      (Arg157Trp) of the PMP22 gene. A heterozygous duplication of the 17p11.2-12
      segment was detected in one offspring of a consanguineous marriage. One patient
      carried a "de novo" heterozygous Ser72Leu substitution in the PMP22. A
      heterozygous double mutation of the P0 gene including a "de novo" Val42 deletion
      and an Ala221Thr substitution, maternally inherited, were found in an apparently
      sporadic case. No mutation of the Egr2 gene was identified. A neuropathy with
      focally folded myelin sheaths (CMT4B) was diagnosed in the nerve biopsy specimens
      of two patients. In five patients, the clinico-pathological findings along with
      the absence of an identified mutation suggested the diagnosis of chronic
      inflammatory demyelinating polyneuropathy of infantile onset. Our findings
      illustrate the genetic heterogeneity of cases with identified mutations, the
      scarcity of cases with "demonstrated" recessive transmission and the likelihood
      of early acquired chronic inflammatory demyelinating polyneuropathy in several
      patients.

PMID- 11596786
TI  - Capgras syndrome in Parkinson's disease.

PMID- 11596787
TI  - Bilateral pallidal lesions following major haemorrhage: description of a case.

PMID- 11596788
TI  - Lesion extension detected by diffusion-weighted magnetic resonance imaging in
      progressive multifocal leukoencephalopathy.

PMID- 11596789
TI  - Sporadic idiopathic cervical dystonia: exclusion of the DYT1 deletion.

PMID- 11596790
TI  - A solitary spinal cord toxoplasma lesion after peripheral stem-cell
      transplantation.

PMID- 11596791
TI  - Extracranial vertebral artery dissection caused by scuba diving.

PMID- 11596792
TI  - Optic neuropathy after treatment with anti-tuberculous drugs in a subject with
      Leber's hereditary optic neuropathy mutation.

PMID- 11596793
TI  - Mieczyslaw Minkowski (1884-1972).

PMID- 11596794
TI  - The effect of arbitration program characteristics on applicants' intentions
      toward potential employers.
AB  - The authors examined intentions toward prospective employers with different
      alternative dispute resolution (ADR) policies and no ADR policy. In Study 1,
      students (N = 124) were randomly assigned to 1 of 4 conditions in which 2
      variables, arbitration policy presence or absence and firm desirability, were
      manipulated. The presence of a voluntary, nonbinding arbitration policy had no
      impact on intentions and did not interact with firm desirability. In Study 2,
      students (N = 273) were randomly assigned to 1 of 8 conditions (mandatory vs.
      voluntary arbitration, binding vs. nonbinding arbitration, and highly desirable
      vs. less desirable employer). Both mandatory and binding arbitration policies
      were related to less favorable intentions toward firms. Predictions regarding the
      interaction of ADR policy and firm desirability were partially supported. Some
      support was found for the interaction between ADR policy and ethnicity.

PMID- 11596795
TI  - Test of a mediated performance-turnover relationship highlighting the moderating
      roles of visibility and reward contingency.
AB  - Despite the importance of understanding the conditions under which high
      performing employees are more likely or less likely to voluntarily leave an
      organization, the nature of the relationship between job performance and
      voluntary turnover has proven to be elusive. A model of the performance-turnover
      relationship that highlights important moderators and mediators is proposed and
      tested. Data consisted of organizational performance and turnover records and
      survey responses for 130 employees of a medical services organization. Results
      indicate that visibility and reward contingencies moderate performance
      relationships with alternatives and job satisfaction, respectively, and that
      performance may influence turnover through multiple mechanisms.

PMID- 11596796
TI  - Knowledge structures and the acquisition of a complex skill.
AB  - The purpose of this study was to examine the viability of knowledge structures as
      an operationalization of learning in the context of a task that required a high
      degree of skill. Over the course of 3 days, 86 men participated in 9 training
      sessions and learned a complex video game. At the end of acquisition,
      participants' knowledge structures were assessed. After a 4-day nonpractice
      interval, trainees completed tests of skill retention and skill transfer.
      Findings indicated that the similarity of trainees' knowledge structures to an
      expert structure was correlated with skill acquisition and was predictive of
      skill retention and skill transfer. However, the magnitude of these effects was
      dependent on the method used to derive the expert referent structure. Moreover,
      knowledge structures mediated the relationship between general cognitive ability
      and skill-based performance.

PMID- 11596797
TI  - The role of personal work goals in newcomers' job satisfaction and organizational
      commitment: a longitudinal analysis.
AB  - This study examined the importance of 3 characteristics of personal work goals
      (i.e., commitment, attainability, and progress) in accounting for changes in
      newcomers' affective job attitudes (i.e., job satisfaction and organizational
      commitment) during the 1st months of employment. Twenty weeks after
      organizational entry, 81 newcomers provided a list of their personal work goals.
      Goal attributes and job attitudes were assessed at 3 testing periods covering 8
      months. Goal commitment was found to moderate the extent to which differences in
      the attainability of personal goals at the workplace accounted for changes in job
      satisfaction and organizational commitment. Goal progress mediated the
      interactive effect of goal commitment and attainability on newcomers' job
      attitudes. Findings are discussed with respect to their relevance for proactive
      approaches to organizational socialization.

PMID- 11596798
TI  - Self-efficacy as a moderator of information-seeking effectiveness.
AB  - The authors assessed previously unexplored processes by which information seeking
      and self-efficacy contribute to self-regulatory effectiveness in industrial
      selling. They assessed the synergistic interaction of inquiry and monitoring with
      respect to role clarity and tested whether this interaction was further moderated
      by self-efficacy. Results indicated that the role-clarifying effects of feedback
      inquiry and monitoring were contingent rather than independent. Role clarity
      increased as the combination of inquiry and monitoring increased. Furthermore,
      these joint effects were moderated by self-efficacy, such that high-self-efficacy
      employees were able to effectively use the combination of inquiry and monitoring
      to clarify role expectations, whereas low-self-efficacy employees were not.
      Implications for theory, practice, and future research are discussed.

PMID- 11596799
TI  - Implementing computerized technology: an organizational analysis.
AB  - Why do some organizations succeed and others fail in implementing the innovations
      they adopt? To begin to answer this question, the authors studied the
      implementation of manufacturing resource planning, an advanced computerized
      manufacturing technology, in 39 manufacturing plants (number of individual
      respondents = 1,219). The results of the plant-level analyses suggest that
      financial resource availability and management support for technology
      implementation engender high-quality implementation policies and practices and a
      strong climate for implementation, which in turn foster implementation
      effectiveness--that is, consistent and skilled technology use. Further research
      is needed to replicate and extend the findings.

PMID- 11596800
TI  - Affective commitment to the organization: the contribution of perceived
      organizational support.
AB  - Three studies examined the interrelationships among work experiences, perceived
      organizational support (POS), affective commitment (AC), and employee turnover.
      Using a diverse sample of 367 employees drawn from a variety of organizations,
      Study 1 found that POS mediated positive associations of organizational rewards,
      procedural justice, and supervisor support with AC. Study 2 examined changes of
      POS and AC in retail employees over a 2-year span (N = 333) and a 3-year span (N
      = 226). POS was positively related to temporal changes in AC, suggesting that POS
      leads to AC. Study 3 found a negative relationship between POS and subsequent
      voluntary employee turnover that was mediated by AC in retail employees (N =
      1,124) and in poultry- and feed-processing workers (N = 262). These results
      suggest that favorable work conditions operate via POS to increase AC, which, in
      turn, decreases employee withdrawal behavior.

PMID- 11596801
TI  - Job search and employment: a personality-motivational analysis and meta-analytic
      review.
AB  - A motivational, self-regulatory conceptualization of job search was used to
      organize and investigate the relationships between personality, expectancies,
      self, social, motive, and biographical variables and individual differences in
      job search behavior and employment outcomes. Meta-analytic results indicated that
      all antecedent variables, except optimism, were significantly related to job
      search behavior, with estimated population correlations ranging from -.15 to .46.
      As expected, job search behavior was significantly and positively related to
      finding employment. Several antecedents of job search were also significantly
      related to employment success, although the size of these relationships was
      consistently smaller than those obtained for job search. Moderator analyses
      showed significant differences in the size of variable relationships for type of
      job search measure (effort vs. intensity) and sample type (job loser vs. employed
      job seeker vs. new entrant).

PMID- 11596802
TI  - Understanding the "personological" basis of employee withdrawal: the influence of
      affective disposition on employee tardiness, early departure, and absenteeism.
AB  - This study investigated the impact of positive affectivity (PA) and negative
      affectivity (NA) on employee tardiness, early departure, and absenteeism,
      controlling for demographic, job-related, and environmental variables. The 3
      temporary withdrawal measures were collected from organizational records in the
      12 months following the survey. The LISREL analysis was based on a sample of 362
      blue-collar employees from a multinational automotive manufacturer. The results
      indicate that individuals high in PA were associated with increased tardiness and
      early departure but decreased absenteeism. Individuals high in NA were associated
      with increased early departure. In terms of moderator effects, job satisfaction
      had a significant negative impact for individuals low in PA in predicting
      tardiness and early departure, whereas job satisfaction displayed a significant
      negative relationship with early departure for individuals high in NA.
      Implications of the findings are discussed.

PMID- 11596803
TI  - The role of participation and control in the effects of computer monitoring on
      fairness perceptions, task satisfaction, and performance.
AB  - Procedural justice and social facilitation theories were used to investigate
      effects of 2 kinds of process control on fairness perceptions, task satisfaction
      and performance of complex, computer-monitored tasks. A laboratory study
      manipulated participation (high or low voice) and monitoring approach
      (monitoring, control over monitoring, or no monitoring). High-voice participants
      perceived higher justice. Monitored participants reported higher satisfaction
      with high voice and lower satisfaction with low voice. Task performance was
      poorer for monitored participants unless they had control over monitoring. Among
      those with control, performance was not impaired for higher baseline performers.
      The 2 kinds of process control had different effects on the outcome variables.
      Results suggest the value of considering variations in the kinds of control
      provided and the justice principles that may apply in predicting effects of
      monitoring procedures.

PMID- 11596804
TI  - Attitudes, self-monitoring, and appraisal behaviors.
AB  - This study examined the influence of attitudes and self-monitoring on leniency
      (elevation accuracy) of performance ratings and personnel decisions. In addition,
      moderating effects of self-monitoring on the relationship between attitudes and
      accuracy of ratings and decisions were investigated. Attitudes and self
      monitoring tendency of 210 managers-professionals were measured, and ratings
      provided and decisions made by them were used to test 3 sets of hypotheses.
      Moderated regression and follow-up split-group analyses indicated that self
      monitoring moderated the relationship between attitudes toward accurate appraisal
      and rating accuracy. Self-monitoring significantly influenced rating and decision
      accuracy such that accuracy declined with increasing level of self-monitoring.
      Results highlight the influence of rater's personality on appraisal behaviors.
      Implications of results and directions for future research are discussed.

PMID- 11596805
TI  - Moderators of the influence of supervisor-subordinate similarity on subordinate
      outcomes.
AB  - Gender, racial, and ethnic similarity were examined for 2,883 subordinate
      supervisor dyads in a military setting. All forms of demographic similarity were
      weakly associated with satisfaction with one's supervisor and continued
      membership in the Army. White subordinates under the supervision of non-Whites
      expressed the lowest level of satisfaction with supervision. Two moderators were
      examined: supervisory support of equal opportunity and the length of time worked
      with a supervisor. Results underscore the value of fine-grained analyses in the
      area of relational demography and the value of studying temporal dynamics
      associated with relational demography.

PMID- 11596806
TI  - Identification and meta-analytic assessment of psychological constructs measured
      in employment interviews.
AB  - There has been a growing interest in understanding what constructs are assessed
      in the employment interview and the properties of those assessments. To address
      these issues, the authors developed a comprehensive taxonomy of 7 types of
      constructs that the interview could assess. Analysis of 338 ratings from 47
      actual interview studies indicated that basic personality and applied social
      skills were the most frequently rated constructs in this taxonomy, followed by
      mental capability and job knowledge and skills. Further analysis suggested that
      high- and low-structure interviews tend to focus on different constructs. Taking
      both frequency and validity results into consideration, the findings suggest that
      at least part of the reason why structured interviews tend to have higher
      validity is because they focus more on constructs that have a stronger
      relationship with job performance. Limitations and directions for future research
      are discussed.

PMID- 11596807
TI  - A meta-analytic review of gender differences in perceptions of sexual harassment.
AB  - Research on gender differences in perceptions of sexual harassment informs an
      ongoing legal debate regarding the use of a reasonable person standard instead of
      a reasonable woman standard to evaluate sexual harassment claims. The authors
      report a meta-analysis of 62 studies of gender differences in harassment
      perceptions. An earlier quantitative review combined all types of social-sexual
      behaviors for a single meta-analysis; the purpose of this study was to
      investigate whether the magnitude of the female-male difference varies by type of
      behavior. An overall standardized mean difference of 0.30 was found, suggesting
      that women perceive a broader range of social-sexual behaviors as harassing.
      However, the meta-analysis also found that the female-male difference was larger
      for behaviors that involve hostile work environment harassment, derogatory
      attitudes toward women, dating pressure, or physical sexual contact than sexual
      propositions or sexual coercion.

PMID- 11596808
TI  - Perceptions of women and men as entrepreneurs: evidence for differential effects
      of attributional augmenting.
AB  - It was hypothesized that perceptions of women who become entrepreneurs are
      enhanced by attributional augmenting because they adopt this role despite major
      obstacles to doing so. In contrast, attributional augmenting was expected to
      operate to a lesser degree for men who become entrepreneurs because they
      presumably face weaker obstacles. Three studies offered support for these
      hypotheses; all of these investigations used between-subjects designs in which
      women and men shown in standard-format photos were described to different groups
      of raters as being either entrepreneurs or managers. As predicted, raters
      assigned significantly higher scores to women, but not to men, when they were
      described as entrepreneurs.

PMID- 11596809
TI  - 360 degree feedback: accuracy, reactions, and perceptions of usefulness.
AB  - This study examined how 360 degree feedback ratings and self-other rating
      discrepancies related to reactions to feedback, perceptions of feedback accuracy,
      perceived usefulness of the feedback, and recipients' receptivity to development.
      The results indicated that less favorable ratings were related to beliefs that
      feedback was less accurate and to negative reactions. Negative reactions and
      perceptions that feedback was less accurate were related to beliefs that the
      feedback was less useful. Those who found feedback less useful were perceived by
      a facilitator as less development-focused. Goal orientation did not moderate the
      relationship between ratings and perceptions of accuracy or reactions to
      feedback. Goal orientation was related to perceptions of usefulness of the
      process several weeks after receipt of feedback. The results question widely held
      assumptions about 360 degree feedback that negative and discrepant feedback
      motivates positive change.

PMID- 11596810
TI  - Effects of the testing situation on item responding: cause for concern.
AB  - The effects of faking on personality test scores have been studied previously by
      comparing (a) experimental groups instructed to fake or answer honestly, (b)
      subgroups created from a single sample of applicants or nonapplicants by using
      impression management scores, and (c) job applicants and nonapplicants. In this
      investigation, the latter 2 methods were used to study the effects of faking on
      the functioning of the items and scales of the Sixteen Personality Factor
      Questionnaire. A variety of item response theory methods were used to detect
      differential item/test functioning, interpreted as evidence of faking. The
      presence of differential item/test functioning across testing situations suggests
      that faking adversely affects the construct validity of personality scales and
      that it is problematic to study faking by comparing groups defined by impression
      management scores.

PMID- 11596811
TI  - Explaining employees' health care costs: a prospective examination of stressful
      job demands, personal control, and physiological reactivity.
AB  - The authors tested the ability of stressful demands and personal control in the
      workplace to predict employees' subsequent health care costs in a sample of 105
      full-time nurses. Both subjective and objective measures of workload demands
      interacted with personal control perceptions in predicting the cumulative health
      care costs over the ensuing 5-year period. Tonic elevations in salivary cortisol,
      moreover, mediated the effects of demands and control on health care costs.
      Neither the job demands variables nor physiological reactivity measures, however,
      explained subsequent mental health. The results support findings from the
      epidemiological literature that demonstrate an important role for employees'
      control in explaining occupational inequalities in coronary heart disease and
      mortality. The authors argue that the results also encourage control-enhancing
      job design interventions by suggesting that their outcomes can benefit both
      organizations and their members.

PMID- 11596812
TI  - An examination of the comparative reliability, validity, and accuracy of
      performance ratings made using computerized adaptive rating scales.
AB  - This laboratory research compared the reliability, validity, and accuracy of a
      computerized adaptive rating scale (CARS) format and 2 relatively common and
      representative rating formats. The CARS is a paired-comparison rating task that
      uses adaptive testing principles to present pairs of scaled behavioral statements
      to the rater to iteratively estimate a ratee's effectiveness on 3 dimensions of
      contextual performance. Videotaped vignettes of 6 office workers were prepared,
      depicting prescripted levels of contextual performance, and 112 subjects rated
      these vignettes using the CARS format and one or the other competing format.
      Results showed 23%-37% lower standard errors of measurement for the CARS format.
      In addition, validity was significantly higher for the CARS format (d = .18), and
      Cronbach's accuracy coefficients showed significantly higher accuracy, with a
      median effect size of .08. The discussion focuses on possible reasons for the
      results.

PMID- 11596813
TI  - Personality moderators of the relationship between abusive supervision and
      subordinates' resistance.
AB  - Results of a study using data collected at 2 points in time, separated by 6
      months, suggested that subordinates resisted their supervisors' downward
      influence tactics with greater frequency when their supervisors were more abusive
      and that subordinates' personality moderated the effects of abusive supervision.
      The relationship between abusive supervision and subordinates' dysfunctional
      resistance was stronger among subordinates who were lower in conscientiousness
      than among subordinates who were higher in conscientiousness, but this effect
      emerged only for subordinates who were also lower in agreeableness. The
      relationship between abusive supervision and subordinates' constructive
      resistance was stronger among subordinates who were higher in conscientiousness
      than among subordinates who were lower in conscientiousness. The study's
      implications for theory and research are discussed.

PMID- 11596814
TI  - The relative importance of task and contextual performance dimensions to
      supervisor judgments of overall performance.
AB  - Although evidence supports the unique contribution of task performance and
      contextual performance to overall evaluations, little is known about the relative
      contribution that specific dimensions of contextual performance make to overall
      performance judgments. This study evaluated the extent to which supervisors
      consider task and contextual performance by using relative weights (J. W.
      Johnson, 2000) to statistically describe the relative importance of specific
      dimensions of each type of performance to overall performance ratings. Within
      each of 8 job families in a large organization, each of 4 dimensions of
      contextual performance made not only a unique contribution but a relatively
      important contribution to the overall evaluation. Evidence also supports the
      adaptive performance dimension of handling work stress as an aspect of contextual
      performance and job-task conscientiousness as an aspect of both task and
      contextual performance.

PMID- 11596815
TI  - Use of a structured investigative protocol enhances young children's responses to
      free-recall prompts in the course of forensic interviews.
AB  - One hundred alleged victims of child sexual abuse (ages 4-12 years; M = 8.1
      years) were interviewed by police investigators about their alleged experiences.
      Half of the children were interviewed using the National Institute of Child
      Health and Human Development's structured interview protocol, whereas the other
      children--matched with respect to their age, relationship with the alleged
      perpetrator, and seriousness of the alleged offenses--were interviewed using
      standard interview practices. Protocol-guided interviews elicited more
      information using open-ended prompts and less information using option-posing and
      suggestive questions than did standard interviews; there were no age differences
      in the amount of information provided in response to open-ended invitations. In
      89% of the protocol interviews, children made their preliminary allegations in
      response to open-ended prompts, compared with 36% in the standard interviews.

PMID- 11596816
TI  - Repetition of attempted suicide among teenagers in Europe: frequency, timing and
      risk factors.
AB  - BACKGROUND: Adolescents in many countries show high rates of suicide attempts and
      repetitions of attempts as a common feature. Attempted suicide is the best
      predictor of future suicide. Repetition of attempts further increases the risk of
      suicide. The present study sought to identify patterns and risk factors for
      repetition of attempts in older teenagers. METHODS: Data were collected by
      uniform procedures in a longitudinal follow-up study in seven European centres
      participating in the WHO/EURO Multicentre Study on Suicidal Behaviour.
      Information on attempted suicide in the 15-19-year age group during the period
      1989-1995 was analysed. RESULTS: A total of 1,720 attempts by 1,264 individuals
      over a mean follow-up period of 204 weeks (SD 108.9) were recorded. When life
      table analysis was performed, 24% of the individuals who had previously attempted
      suicide made another attempt within one year after the index attempt, compared
      with 6.8% of the "first-evers", with no major gender difference. Cox regression
      analysis revealed that previous attempted suicide (OR 3.3, 95% CI 2.4-4.4) and
      use of "hard" methods (OR 1.5, 95% CI 1.1-2.1) were both significantly associated
      with repetition of attempted suicide. Stepwise Cox regression analysis showed
      that a history of previous attempted suicide was the most important independent
      predictor of repetition (OR 3.2, 95% CI 2.4-4.4). CONCLUSION: For young suicide
      attempters, follow-up and adequate aftercare are very important if repetition and
      risk of suicide are to be reduced. This applies particularly to those who have
      already made more than one attempt.

PMID- 11596817
TI  - Family functioning in adolescents at high and low risk for major depressive
      disorder.
AB  - Families of two subgroups of adolescents in the community, at high and low risk
      for major depressive disorder, were compared on the McMaster Family Assessment
      Device (FAD) and the General Health Questionnaire (GHQ). Families of high-risk
      adolescents who became depressed by follow-up at one year were compared with
      other families of high-risk subjects. The only significant difference on FAD
      ratings for high- and low-risk groups was on the sub-scale Roles as reported by
      mothers. FAD ratings showed that, compared with mothers, fathers of high-risk
      adolescents held significantly worse views of their families' functioning on the
      sub-scales Problem Solving, Affective Responsiveness and Behaviour Control. There
      were no such differences between low-risk parents. Both mothers and fathers of
      high-risk adolescents reported their own mental health as significantly poorer
      than mothers and fathers of low-risks. The mental health of mothers in the high
      risk group only was significantly associated with their FAD ratings. Adolescents
      rated their families as significantly worse on the FAD than their parents and the
      lower their mood and self-esteem, the worse they rated their families on the FAD.
      Subsequent MDD in adolescents by follow-up at one year was not associated with
      the FAD scores of any family member, nor with either parent's mental health.

PMID- 11596818
TI  - Self-reported strengths and difficulties in a community sample of Finnish
      adolescents.
AB  - The psychometric properties of the self-report version of the Strengths and
      Difficulties Questionnaire (SDQ) among Finnish 13- to 17-year-old adolescents (n
      = 1,458) were studied. The results show that the psychometric properties of the
      Finnish SDQ self-report were adequate. The results of the correlation analysis
      confirmed the postulated structure of the SDQ self-report. The correlations of
      the items to their respective subscales ranged from moderate to high (r = 0.47
      0.73). The internal consistency was acceptable on three and somewhat lower on two
      of the five subscales (alpha=0.53-0.71). In addition, the factor analysis
      sufficiently confirmed the postulated structure of the SDQ for girls and boys,
      except for the conduct problems scale of boys, which was fused with emotional
      symptoms and with hyperactivity. The means of the SDQ self-report total
      difficulties scores were very similar to those in a previous study in Great
      Britain. The results provide additional confirmation of the usefulness of the SDQ
      as a screening instrument in epidemiological research and clinical practice.

PMID- 11596819
TI  - Self-reported competencies and problems among Swedish adolescents: a normative
      study of the YSR. Youth Self Report.
AB  - The aim of the study was to provide a standardisation of self-reported
      competencies and emotional/behavioural problems among Swedish adolescents, using
      the Youth Self-Report (YSR). The YSR was completed by 2522 adolescents aged 13-18
      years, recruited from secondary and upper secondary schools in different regions
      in Sweden. The results showed that effects of gender and age were small but
      significant with girls scoring higher than boys on most problem scales, and 15-
      to 16-year-olds scoring higher than younger and older adolescents on the problem
      scales. Small effects were also found for residence as well as for parental SES.
      The correlations between internalising and externalising problems were 0.51 for
      boys and 0.49 for girls, whereas the correlation between competence and problem
      scores was low. We conclude that the individual variation in YSR-scores is much
      greater than can be attributed to factors such as gender, age, SES, or
      residential area. Consequently, the YSR has the potential to serve as an
      instrument for assessing individual adolescents' self-reported competencies and
      problems in Sweden. Given the almost orthogonal relation between self-reported
      competencies and problems, the competence scale is surprisingly little used in
      psychopathology research.

PMID- 11596820
TI  - Folie a famille and separation-individuation.
AB  - The case history, treatment and follow-up of a family sharing the same delusion
      are presented in this article. The characteristics of separation-individuation of
      this pathological condition and its treatment are discussed.

PMID- 11596821
TI  - Obsessive-compulsive disorder and acquired toxoplasmosis in two children.
AB  - Two children presenting symptoms of obsessive-compulsive disorder (OCD) and with
      acquired toxoplasmosis are described and the possibility of a previously rarely
      reported association between OCD and acquired toxoplasmosis is discussed. Case 1
      is a 14-year-old boy with Tourette syndrome (TS), attention deficit hyperactivity
      disorder (ADHD) in partial remission and a three-year history of OCD referred to
      our department due to an acute deterioration of obsessive-compulsive (OC)
      symptoms. Case 2 is an 11-year-old boy referred to our department because of a
      two-year history of OCD. The OC symptoms were observed immediately following an
      infection. In both cases laboratory tests confirmed the diagnosis of acquired
      toxoplasmosis. The pharmacological therapy of T.gondi infection without any
      psychopharmacological treatment caused remission or significant improvement
      regarding OC symptoms.

PMID- 11596822
TI  - Olanzapine induces remarkable weight gain in adolescent patients.
AB  - We present here clinical case reports of three adolescents, aged 14-17 years, who
      were treated with olanzapine. The daily dose was 10 mg. Prior to olanzapine, the
      patients were unsuccessfully treated with other antipsychotic drugs. The response
      to olanzapine for psychotic symptoms was clinically significant in all three
      patients. The major adverse effect was excessive weight gain. The increases in
      body mass index (BMI) were 9, 8 and 5 kg/m2. One of the patients later lost the
      additional weight. Especially in adolescents obesity is a serious side effect and
      potential consequences include numerous health problems.

PMID- 11596823
TI  - Clozapine and therapy-refractory epileptic seizures.

PMID- 11596824
TI  - The training  logbook of UEMS section/board on child and adolescent psychiatry
      (CAPP) progress concerning European harmonization.

PMID- 11596825
TI  - Posthypnotic amnesia for material learned before or during hypnosis: explicit and
      implicit memory effects.
AB  - This article focuses on dissociations between explicit and implicit expressions
      of memory during posthypnotic amnesia (PHA). Despite evidence of such
      dissociations, experimental design in this area has not always been consistent
      with contemporary memory research. Within a paradigm that aimed for conceptual
      and methodological clarity, we presented 40 high and 38 low hypnotizable
      individuals with a word list either before or during hypnosis, gave them a PHA
      suggestion for the word list, and tested them on explicit and implicit memory
      tasks. In the absence of conscious recollection, highs showed equivalent levels
      of priming (perceptual and semantic) to lows. However, when analysis focused only
      on those highs who remained amnesic after the implicit memory tasks, we confirmed
      perceptual, but not semantic, priming. These findings highlight the impact of
      methodological choices on theoretical interpretations of memory performance
      following a suggestion for PHA.

PMID- 11596826
TI  - The hypnotic dreams of healthy children and children with cancer: a quantitative
      and qualitative analysis.
AB  - In this study, the Stanford Hypnotic Clinical Scale for Children was administered
      to 52 healthy children and 47 children and adolescents with cancer. Responses to
      the dream item of this scale were analyzed for the type and detail of imagery.
      The hypnotizability scores of both groups were similar. However, children with
      cancer reported more pleasant than unpleasant fantasy in their hypnotic dreams,
      and their dream reports tended to contain less fantasy and detail overall.
      Rescoring the dream item based on extent of fantasy and detail resulted in a
      lower pass rate for that item, especially for children with cancer. Regardless of
      health status, older children experienced more self-involvement in their hypnotic
      dreams compared to younger children.

PMID- 11596827
TI  - Frontal lobe contributions to hypnotic susceptibility: a neuropsychological
      screening of executive functioning.
AB  - Current theory on the cognitive mechanisms of hypnotic experience suggests that
      hypnosis is mediated by a dissociation between contention-scheduling mechanisms
      and a supervisory attention system. This theory is based on neuropsychological
      research with frontal lobe dysfunction patients, who show performance deficits
      similar in executive functioning to hypnotized individuals. To test an extension
      of this theory, high hypnotically susceptible (n = 9) and low hypnotically
      susceptible (n = 7) participants were given four tests of executive functioning.
      In a baseline condition, high susceptible individuals performed significantly
      better on one of the four tests (the Wisconsin Card Sorting Test). The role of
      increased cognitive flexibility in hypnotic susceptibility is considered as a
      possible component of the dissociated control model of hypnosis.

PMID- 11596828
TI  - Hypnotic color blindness and performance on the Stroop test.
AB  - A suggestion for hypnotic color blindness was investigated by administering a
      reverse Stroop color-naming task. Prior to the suggestion for color blindness,
      participants learned associations between color names and shapes. Following the
      color blindness suggestion, participants were required to name the shapes when
      they appeared in colors that were either congruent or incongruent with the
      learned associations. The 18 high hypnotizable participants who passed the
      suggestion were slower to name (a) shapes in which the color name was incongruent
      with the color in which it was printed, (b) "unseen" rather than "seen" shapes,
      and (c) color-incongruent shapes that were printed in the color in which they
      were "color-blind." These patterns are discussed in terms of potential cognitive
      and social mechanisms that may mediate responses to hypnotic color blindness.

PMID- 11596829
TI  - Being "the other therapist": the varieties of adjunctive experience with
      hypnosis.
AB  - Clinicians who utilize hypnosis in their practices are frequently approached with
      requests to participate in the care of patients who are currently in treatment
      with a primary therapist. Surprisingly, a review of the literature indicated that
      no research has been done on this common practice. This article provides a
      discussion of some of the important issues as well as the variables to consider
      in deciding whether to enter into this arrangement. It will serve as a starting
      point in generating further research on this crucial topic.

PMID- 11596830
TI  - Matching hypnotic interventions to pathology types: a working model for
      expressive psychotherapies.
AB  - This article identifies Kohut's typology of Guilty Man and Tragic Man as a
      clinically useful construct in outpatient psychotherapy. The author notes that an
      expressive approach focused on ambivalent conflict is indicated for the Guilty
      Man, and a restructuring expressive approach is indicated for the Tragic Man. A
      hypnosis technique is identified for use with each of these two approaches: the
      Door of Forgiveness technique (primarily for conflict-focused therapies) and the
      Conference Table Technique (for restructuring therapies).

PMID- 11596831
TI  - Pharmacoeconomic fellowships: the need for outcome measures.
AB  - Pharmacoeconomic fellowship programmes have been in existence for more than 10
      years, but their effectiveness has not been evaluated. The aim of this project
      was to construct a framework to examine the potential outcome measures for
      pharmacoeconomic fellowships so that the effectiveness of these programmes may be
      determined. Using the Donabedian model, the structures, processes, and outcomes
      of pharmacoeconomic fellowship programmes were investigated. The structures of
      these programmes include the facilities, qualifications of the teaching staff and
      organisation, and operations of the institution. Most pharmacoeconomic
      fellowships are based in academic institutions and the pharmaceutical industry.
      Credentials of the preceptors and teaching staff consist of an advanced degree
      and relevant expertise in pharmacoeconomics and outcomes research. The processes
      of pharmacoeconomic fellowships include the duration of the programme as well as
      the research skills and the educational components taught. However, current
      guidelines do not define outcome measures for these pharmacoeconomic fellowships.
      Potential outcomes may include whether or not a degree was obtained, the
      management and research skills acquired, as well as the type of experiential
      training received. Further research is required to develop these outcome
      measures, so the effectiveness of pharmacoeconomic fellowship programmes may be
      assessed.

PMID- 11596832
TI  - The impact of health economics on healthcare delivery: the health economists'
      perspective.

PMID- 11596833
TI  - A review of the direct costs of rheumatoid arthritis: managed care versus fee-for
      service settings.
AB  - Rheumatoid arthritis (RA) is a prevalent condition associated with pain, joint
      destruction and morbidity. Direct healthcare costs are 2 to 3 times higher than
      average costs for individuals of similar age and gender. Furthermore, utilisation
      and costs rise with age and disease duration. Managed care has become an
      increasingly popular way to organise and finance the delivery of healthcare.
      Studies comparing the quality of care in health maintenance organisations and fee
      for-service settings have found few differences in outcomes, although reduced
      costs have been attributed to lower hospitalisation rates in patients with RA. We
      reviewed 10 studies of the direct costs of RA. In 1996 dollars, direct costs
      ranged from $US 2,299 per person per year in Canada to $US 13,549 in a US study
      focusing on patients who have been hospitalised only. Surprisingly, the
      contributions to direct costs--hospital care, medications and physician visits-
      remained relatively stable over time and the setting of care. Hospitalisation
      costs were the highest component of direct costs accounting, generally, for 60%
      or more of costs while only approximately 10% of patients with RA were
      hospitalised. The only exception was a managed care setting where hospitalisation
      costs were 16% of total direct costs. In managed care settings, costs of
      medications were proportionately higher than in fee-for-service settings. We
      conclude that in studies of the direct costs of RA the components of costs have
      remained relatively stable over time. This may change with the development and
      growing use of new RA medications including cyclo-oxygenase 2 inhibitors,
      interleukins, cytokines, treatments that inhibit tumour necrosis factor, and
      combination therapies. The effectiveness of managed care in controlling direct
      costs needs to be evaluated in more targeted studies.

PMID- 11596834
TI  - The cost effectiveness of stratified care in the management of migraine.
AB  - OBJECTIVE: To examine the cost effectivess of a stratified-care regimen for
      patients with migraine--in which patients are stratified by severity of illness,
      and then prescribed differing treatments according to level of severity--compared
      with a conventional stepped-care approach. DESIGN AND METHODS: A decision
      analytic model was constructed to simulate a controlled clinical trial in which
      patients with migraine receiving primary medical care were randomly assigned to
      treatment under a stepped-care or a stratified-care regimen. A health service
      payer perspective was adopted and the time horizon was 1 year. Data inputs were:
      (i) the frequency and disability of migraine, derived from population-based
      studies; (ii) disability level-specific treatment response rates for over-the
      counter analgesics,aspirin/metoclopramide and zolmitriptan as the representative
      of high-end therapy obtained from an international consensus opinion enquiry; and
      (iii) unit costs of healthcare obtained from UK health service sources. MAIN
      OUTCOME MEASURES AND RESULTS: The estimated 1-year direct healthcare costs per
      primary care patient with migraine were pound sterling 156.82 for stepped care
      and sterling pound 151.57 for stratified care. Estimates of treatment response
      rates were 40 and 71% for stepped and stratified care, respectively. The cost per
      successfully treated attack was sterling pound 23.43 for stepped care and
      sterling pound 12.60 for stratified care. Stratified care remained cost effective
      when tested in a wide range of one-way sensitivity analyses, and probabilistic
      sensitivity analysis showed the cost effectiveness of stratified care to be
      significant at the 3% level. Conditional confidence analysis showed that the
      level of confidence in the cost effectiveness of stratified care varied
      positively with the case mix, i.e. in populations where the proportion of
      moderate and severely disabled patients with migraine was greater than 25%, the
      cost effectiveness of stratified care remained statistically significant.
      CONCLUSION: A stratified-care treatment strategy (including zolmitriptan as the
      representative of high-end therapy) is a highly cost-effective method of managing
      migraine in the primary care setting compared with stepped care, delivering
      improved clinical outcomes at no additional cost.

PMID- 11596835
TI  - Cost effectiveness in Canada of a multidrug prepackaged regimen (Hp-PAC)+ for
      Helicobacter pylori eradication.
AB  - OBJECTIVE: To assess the cost effectiveness of a multidrug prepackaged regimen
      for Helicobacter pylori, the Hp-PAC (lansoprazole 30mg, clarithromycin 500 mg,
      amoxicillin 1 g, all twice daily), relative to alternative pharmacological
      strategies in the management of confirmed duodenal ulcer over a 1-year period
      from 2 perspectives: (i) a strict healthcare payer perspective (Ontario Ministry
      of Health) excluding the patient copayment; and (ii) a healthcare payer
      perspective including the patient copayment. DESIGN: A decision-analytical model
      was developed to estimate expected per patient costs [1998 Canadian dollars ($
      Can)], weeks without ulcer and symptomatic ulcer recurrences for the Hp-PAC
      compared with: proton pump inhibitor (PPI)-clarithromycin-amoxicillin (PPI-CA),
      PPI-clarithromycin-metronidazole (PPI-CM), PPI-amoxicillin-metronidazole (PPI-AM)
      and ranitidine-bismuthmetronidazole-tetracycline (RAN-BMT). MAIN OUTCOME MEASURES
      AND RESULTS: All PPI-based regimens had higher expected costs but better outcomes
      relative to RAN-BMT. From a strict healthcare payer perspective, PPI-CM ($Can
      209) yielded lower expected costs than PPI-CA ($Can 221) and slightly lower costs
      than Hp-PAC ($Can 211). However, these 3 regimens all shared identical outcomes
      (51.2 weeks without ulcer). When the current Ontario, Canada, $Can 2 patient
      copayment was added to the dispensing fee, Hp-PAC yielded lower costs ($Can 214)
      than PPI-CM ($Can 216). CONCLUSION: From a strict healthcare payer perspective,
      Hp-PAC is weakly dominated by PPI-CM with an incremental cost effectiveness
      (relative to RAN-BMT) of $Can 5.77 per ulcer week averted. When the patient
      copayment is added to this perspective, Hp-PAC weakly dominates PPI-CM ($Can 5
      per ulcer week averted). Regardless of perspective, Hp-PAC and PPI-CM differed by
      only $Can 2 per patient over 1 year and the expected time without ulcer was 51.2
      weeks for both. More data on the clinical and statistical differences in H.
      pylori eradication with Hp-PAC and PPI-CM would be useful. This analysis does not
      in clude the possible advantage of Hp-PAC in terms of compliance and
      antibacterial resistance.

PMID- 11596836
TI  - Incremental cost analysis of ambulatory clinic and home-based intravenous therapy
      for patients with multiple myeloma.
AB  - BACKGROUND: Patients with multiple myeloma and other forms of cancer receiving
      pamidronate via intravenous (IV) infusion at the Hamilton Regional Cancer Centre
      in Hamilton, Ontario, Canada face 2 treatment options: they can have their entire
      treatment completed at the clinic using traditional IV therapy (e.g. IV bag and
      pole) or they can have the treatment initiated at the clinic and then return home
      to complete the treatment utilising a portable and disposable IV therapy device.
      OBJECTIVE: To perform a cost analysis of these 2 treatment options. PERSPECTIVE:
      Societal. METHODS AND PATIENTS: Data on all patients with multiple myeloma who
      attended the Hamilton Regional Cancer Centre for pamidronate therapy from
      November 1, 1997 to October 31, 1998 were collected from clinic records. As
      almost all of these patients with multiple myeloma completed their IV therapy at
      home, comparison to clinic-based therapy was based on derived cost estimates.
      Cost data, where possible, were acquired from the Hamilton Regional Cancer
      Centre's records. A sensitivity analysis was also conducted. RESULTS: In the base
      case scenario for the study period, the incremental cost of the infusion device
      and training in Canadian dollars ($Can; 1998 values) for the 48 patients (299
      cycles) who had their infusion initiated at the clinic but completed at home was
      $Can 5.50/cycle ($Can 4,636 for the 299 cycles). If these 48 patients had had
      their entire infusion at the clinic, the incremental costs of overtime treatment,
      parking, clinic overheads and lost work or leisure time would have been $Can
      68.49/cycle ($Can 20,477 for the 299 cycles). Therefore, shifting treatment from
      the clinic to the home resulted in net cost savings to society of $Can
      52.98/cycle ($Can 15,841 for the 299 cycles). Sensitivity analysis of best- and
      worst-cost scenarios did not alter the substantive findings although the relative
      difference between treatment options varied. In the best-case scenario, home
      treatment was $Can 95.97/cycle ($Can 28,696 for the 299 cycles) less costly than
      clinic treatment, while in the worst-case scenario, home treatment was $Can
      17.19/cycle ($Can 5,141 for the 299 cycles) less costly than clinic treatment.
      The results also demonstrated that clinic overheads, the cost of a portable and
      disposable infusion device and the cost of lost work and leisure time had the
      greatest impact on incremental costs for each treatment option. CONCLUSION:
      Subject to study limitations, a significant cost advantage was demonstrated
      through the home-based treatment option for patients with multiple myeloma. Key
      issues that must be addressed in future evaluations include the precise
      determination of clinic overheads, the valuation of lost work and/or leisure time
      and the direct cost of portable and disposable infusion devices.

PMID- 11596837
TI  - Quality of life and utility in patients with non-small cell lung cancer. Quality
      of-life Study Group of the Master 2 Project in Pharmacoeconomics.
AB  - BACKGROUND: Although several studies have determined quality of life in patients
      with lung cancer, there is still little information about the use of generic
      questionnaires [e.g. the 36-item Short Form health survey (SF-36)] and utility
      questionnaires [e.g. the EuroQOL instrument (EQ-5D)] in this disease. OBJECTIVES:
      To (i) measure quality of life and utility in patients with non-small cell lung
      cancer (NSCLC) using the SF-36 and the EuroQOL questionnaires; (ii) to evaluate
      the impact of some clinical variables on quality of life and utility; (iii) to
      assess the correlation between the measurements produced by the 2 questionnaires.
      STUDY DESIGN: Cross-sectional study. PARTICIPANTS: 95 patients from 15 Italian
      hospitals with NSCLC (93% male, mean age 62 years) completed both questionnaires.
      RESULTS: The mean scores for the 8 domains of the SF-36 ranged from 20.8
      (physical role) to 63.0 (social functioning). The mean physical and mental summed
      scores of the SF-36 were 36.8 [standard deviation (SD) 9.8] and 43.0 (SD 11.5),
      respectively. The EuroQOL mean score was 0.58 (SD 0.32) in the self-classifier
      (SC) version and 0.58 (SD 0.20) in the visual analogue scale (VAS) version. Among
      the clinical variables that affected quality of life and utility, the presence of
      metastasis had the greatest impact: patients with metastasis had statistically
      significantly lower scores for 2 domains of the SF-36 (physical functioning, p =
      0.009; bodily pain, p = 0.016), for the physical component summed score of the SF
      36 (p = 0.015) and for both utility estimates (EuroQOL-SC, p = 0.027; EuroQOL
      VAS, p = 0.038) than patients without metastasis. Both the SC and VAS EuroQOL
      scores showed a statistically significant correlation with each of the 8 domains
      of the SF-36. The scores for both the SF-36 and the EuroQOL in patients with
      NSCLC were considerably worse (relative differences ranging from -8 to -73%) than
      the corresponding values (normative data) previously reported for healthy
      individuals. CONCLUSIONS: Our study quantified the degree to which quality of
      life is impaired in patients with NSCLC, showed that the presence of metastasis
      had an important role, and indicated a strong correlation between the
      measurements produced by the 2 questionnaires. The EuroQOL measurements obtained
      from these patients will aid evaluation of the cost-utility ratio for NSCLC
      therapies.

PMID- 11596838
TI  - Cost-efficacy analysis of fluticasone propionate versus zafirlukast in patients
      with persistent asthma.
AB  - OBJECTIVE: To compare the relative value of an inhaled corticosteroid,
      fluticasone propionate 88 microg twice daily, versus an oral leukotriene receptor
      antagonist, zafirlukast 20 mg twice daily, in patients with persistent asthma
      currently receiving short acting beta2-agonists alone. STUDY DESIGN: A cost
      efficacy analysis using resource utilisation and clinical data obtained
      prospectively from a multicentre, randomised, double-blind, double-dummy, placebo
      controlled 12-week clinical trial conducted in the US. PERSPECTIVE: Third-party
      payor. PATIENTS AND METHODS: A total of 451 corticosteroid-naive patients with
      persistent asthma were treated with either fluticasone propionate 88 microg twice
      daily or zafirlukast 20 mg twice daily. All patients were given salbutamol
      (albuterol) to be used as rescue medication. Data were examined using intent-to
      treat analysis. RESULTS: Mean daily per person cost-efficacy ratios using
      improvement in forced expiratory volume in 1 second (FEV1) [> or = 12% increase
      from baseline] were $US 3.47 for fluticasone propionate compared with $US 7.81
      for zafirlukast (1999 values). The mean daily per person cost-efficacy ratios for
      symptom-free days obtained were $US 5.51 for fluticasone propionate compared with
      $US 14.98 for zafirlukast. These cost-efficacy ratios remained in favour of
      fluticasone propionate after a robust sensitivity analysis. CONCLUSIONS:
      Treatment with fluticasone propionate 88 kg twice daily was the most cost
      effective treatment compared with zafirlukast 20 mg twice daily in this 12-week
      clinical trial. This analysis supports the use of fluticasone propionate 88
      microg twice daily as first-line treatment in patients with persistent asthma
      previously treated with short-acting beta2-agonist alone.

PMID- 11596839
TI  - Cost-effectiveness analysis of dopamine agonists in the treatment of Parkinson's
      disease in Japan.
AB  - BACKGROUND: Dopamine agonists such as bromocriptine or pergolide are often used
      in Japan to treat Parkinson's disease. Dopamine agonists are relatively expensive
      drugs; economic evaluations are required. OBJECTIVE: To evaluate the cost
      effectiveness of dopamine agonists for the treatment of Parkinson's disease in
      Japan. DESIGN AND SETTING: We used a Markov model to simulate the course of
      Parkinson's disease and to compare the cost effectiveness of dopamine agonists
      added to levodopa with that of levodopa alone in Japan. The model assumed that 60
      year-old men with Parkinson's disease in Hoehn-Yahr (HY) stages 2 to 5 using
      levodopa were administered dopamine agonists or continued on levodopa alone. The
      incremental cost effectiveness of dopamine agonists used for 10 years was then
      estimated. STUDY PERSPECTIVE: Societal. MAIN OUTCOME MEASURES AND RESULTS: In the
      patients in HY stage 2, the incremental cost effectiveness of dopamine agonists
      was 18,610,000 to 19,320,000 yen per quality-adjusted life-year (QALY) [$US
      172,300 to $US 178,900/QALY; 1998 values] . In patients in HY stage 3 or higher,
      the use of dopamine agonists was dominant over levodopa alone mainly due to
      reduced cost for care. In sensitivity analyses, costs and effectiveness of
      dopamine agonists significantly influenced the results. The use of a generic
      formulation of bromocriptine was dominant over levodopa alone even in the
      patients with HY stage 2 disease. CONCLUSIONS: Dopamine agonists appear to be
      cost effective in advanced Parkinson's disease, although their use is sensitive
      to the costs and effectiveness of dopamine agonists. If factors discouraging the
      prescription of generic drugs in Japan were removed, the treatment of Parkinson's
      disease would become more cost effective.

PMID- 11596840
TI  - Early brain wiring: activity-dependent processes.
AB  - One of the leading theories of the neuropathology of schizophrenia is that it is
      a developmental disorder of "neural connectivity." To assess this theory, it is
      first necessary to understand how precise neural connections normally are
      established. Sensory-driven neural activity has been widely recognized as crucial
      for this process. Recent studies have revealed a similar requirement for
      endogenous neural activity generated by the nervous system itself, long before
      there is any sensory input. These patterns of sensory-driven and endogenously
      generated neural activity sculpt the precise circuits that are crucial to the
      many complex functions of the adult brain. This article summarizes the principles
      of activity-dependent neural development as determined from basic neuroscience
      experiments, particularly those done using the mammalian visual system, to
      illustrate the role of patterned activity, neuronal competition, and critical
      periods in shaping neural circuitry. The potential molecular mechanisms involved
      in these features of activity-dependent neurodevelopment are discussed and
      possible links to the etiology of schizophrenia are briefly explored.

PMID- 11596841
TI  - Regionally diverse cortical pathology in schizophrenia: clues to the etiology of
      the disease.
AB  - Perhaps the most surprising revelation that has emerged from recent pathologic
      studies of schizophrenia is the marked cortical regional heterogeneity of the
      disease. Areal specific alterations of many parameters have been reported (e.g.,
      neuronal density, density of gamma-aminobutyric acid [GABA]-immunoreactive cells,
      and concentration of synapse-associated proteins and messenger ribonucleic acid
      [mRNA]s). In the past 5 years, as a flood of seemingly contradictory findings
      have been published, divergent findings often have been regarded as further
      evidence of the irreplicability and futility of postmortem studies. Although some
      discrepancies in findings may be due to methodological differences or to the
      study of different cohorts of patients, a growing number of laboratories are
      examining the same parameter(s) in multiple cortical areas in a single brain
      cohort and finding regionally specific abnormalities. These findings provide
      compelling evidence that cortical pathology in schizophrenia is nonuniform and
      complex. A major challenge in contemporary schizophrenia research is to make
      sense of the patterning of whole brain pathology in schizophrenia, as the mosaic
      of neuropathologic alterations may provide clues to the disease etiology.

PMID- 11596843
TI  - Challenges, status, and opportunities for studying developmental neuropathology
      in adult schizophrenia.
AB  - Neurodevelopmental theories of the pathoetiology of schizophrenia have been at
      the forefront of schizophrenia research in recent years. Support for these
      theories is substantial and growing. Epidemiological, phenomenological, and
      clinical neurobiological research have provided compelling though still
      circumstantial evidence. Neuropathological investigations also have provided some
      evidence; however, these have yet to actualize their potential for revealing the
      cellular and molecular nature of developmental aberrancies in this disease. This
      article summarizes the clinical evidence suggesting abnormal neurodevelopment in
      schizophrenia, outlines some of the important anatomic, cellular, and molecular
      mechanisms of normal central nervous system development, reviews current
      neuropathological findings relevant to neurodevelopment in schizophrenia, and
      suggests some new directions and opportunities for discovering the molecular
      neurodevelopmental basis of the disorder.

PMID- 11596844
TI  - Genetic insights into the neurodevelopmental hypothesis of schizophrenia.
AB  - The original neurodevelopmental hypothesis of schizophrenia presented by D.R.
      Weinberger in 1987 focused on pathogenesis and did not address etiology.
      Available evidence indicates that genetic factors are the principal cause of
      schizophrenia. It is imperative that any pathogenetic model for schizophrenia
      takes into account what is now known about genetic mechanisms of illness. Recent
      advances in molecular genetics can provide insights into the neurodevelopmental
      expression of the illness and what future genetic discoveries are likely to
      contribute to our understanding of schizophrenia. In this article, we propose a
      genetic model of etiopathogenesis that is consistent both with a modified
      neurodevelopmental hypothesis and our current knowledge about schizophrenia and
      molecular genetics.

PMID- 11596845
TI  - Mesoprefrontal dopamine neurons and schizophrenia: role of developmental
      abnormalities.
AB  - Schizophrenia is characterized by a complex array of symptoms that include
      hallucinations, delusions, abnormal affect, and cognitive deficits. It is
      becoming increasingly apparent that the symptoms of the disorder are paralleled
      by equally complex functional and structural abnormalities in brain regions such
      as the temporal lobe, prefrontal cortex, and thalamus. In addition, the delayed
      onset of symptoms in late adolescence/early adulthood suggests that abnormal
      development of the nervous system may ultimately contribute to the neurobiology
      of the disorder. The present review focuses on clinical and basic research that,
      together, suggests abnormal development of the dopamine (DA) innervation of
      prefrontal cortex plays a role in the cognitive deficits of schizophrenia.

PMID- 11596842
TI  - Paternal factors and schizophrenia risk: de novo mutations and imprinting.
AB  - There is a strong genetic component for schizophrenia risk, but it is unclear how
      the illness is maintained in the population given the significantly reduced
      fertility of those with the disorder. One possibility is that new mutations occur
      in schizophrenia vulnerability genes. If so, then those with schizophrenia may
      have older fathers, because advancing paternal age is the major source of new
      mutations in humans. This review describes several neurodevelopmental disorders
      that have been associated with de novo mutations in the paternal germ line and
      reviews data linking increased schizophrenia risk with older fathers. Several
      genetic mechanisms that could explain this association are proposed, including
      paternal germ line mutations, trinucleotide repeat expansions, and alterations in
      genetic imprinting in one or several genes involved in neurodevelopment. Animal
      models may be useful in exploring these and other explanations for the paternal
      age effect and they may provide a novel approach for gene identification.
      Finally, it is proposed that environmental exposures of the father, as well as
      those of the mother and developing fetus, may be relevant to the etiology of
      schizophrenia.

PMID- 11596846
TI  - Studies of brain and cognitive maturation through childhood and adolescence: a
      strategy for testing neurodevelopmental hypotheses.
AB  - Although neurodevelopmental models of schizophrenia are now widely accepted,
      there is minimal direct human evidence of dysmaturation in schizophrenia to
      support this theory. This is especially the case regarding maturational changes
      during late childhood and adolescence, which immediately precede the typical age
      of onset of the disorder. By integrating new noninvasive methods of functional
      magnetic resonance imaging with techniques of developmental cognitive
      neuroscience, it is now possible to begin systematic research programs to
      directly test hypotheses of neurodevelopmental abnormalities in schizophrenia. In
      this article, we describe strategies for characterizing developmental changes
      taking place during the critical period of adolescence that can elucidate
      dysmaturation processes in schizophrenia. We emphasize the need for studies
      characterizing normal development before examining at-risk or clinical
      populations, and the potential value of using neurobehavioral and neuroimaging
      approaches to directly characterize the dysmaturation associated with
      schizophrenia.

PMID- 11596847
TI  - Neural development, cell-cell signaling, and the "two-hit" hypothesis of
      schizophrenia.
AB  - To account for the complex genetics, the developmental biology, and the late
      adolescent/early adulthood onset of schizophrenia, the "two-hit" hypothesis has
      gained increasing attention. In this model, genetic or environmental factors
      disrupt early central nervous system (CNS) development. These early disruptions
      produce long-term vulnerability to a "second hit" that then leads to the onset of
      schizophrenia symptoms. The cell-cell signaling pathways involved in nonaxial
      induction, morphogenesis, and differentiation in the brain, as well as in the
      limbs and face, could be targets for a "first hit" during early development.
      These same pathways, redeployed for neuronal maintenance rather than
      morphogenesis, may be targets for a "second hit" in the adolescent or adult
      brain. Furthermore, dysregulation of cell-cell signaling by a "first hit" may
      prime the CNS for a pathologic response to a "second hit" via the same signaling
      pathway. Thus, parallel disruption of cell-cell signaling in both the developing
      and the mature CNS provides a plausible way of integrating genetic,
      developmental, and environmental factors that contribute to vulnerability and
      pathogenesis in schizophrenia.

PMID- 11596848
TI  - At issue: stress, hippocampal neuronal turnover, and neuropsychiatric disorders.
AB  - Stress-induced changes in the glucocorticoid system may be toxic for hippocampal
      cells in animals. Recently, neurogenesis has been shown in the rat, the primate,
      and the human hippocampus. Because chronic stress is associated with some
      neuropsychiatric disorders, including schizophrenia, it is possible that an
      imbalance in the normal turnover of hippocampal cells plays a role in the
      pathophysiology not only of schizophrenia but also of other neuropsychiatric
      disorders that involve high levels of stress. New therapeutic possibilities arise
      if such a process is proven to occur.

PMID- 11596849
TI  - Speech disorder in schizophrenia: review of the literature and exploration of its
      relation to the uniquely human capacity for language.
AB  - The language capacity of modern humans is thought by some to be clearly distinct
      from that of nonhuman primates (Bickerton 1990). Crow (1997, 1998a) has proposed
      that a disturbance in the uniquely human aspects of language is central to the
      genetic etiology of schizophrenia. A review of the literature on language
      disorder in schizophrenia provides evidence for widespread deficits in
      comprehension, production, attention, and cerebral lateralization of language. We
      focused here on those anomalies that are uniquely human aspects of language.
      Bickerton's five distinctly human language devices were examined in patients with
      schizophrenia and their families by using a structured scoring format on oral
      soliloquies. The chronic patients showed reduced use of clausal embedding and
      used fewer words than first episode patients or well family members. The amount
      of sentence complexity was found to be familial and to cosegregate with
      schizophrenia within families. These data are consistent with previous literature
      and additionally show a familial component to these measures, thus suggesting
      that deficits in specifically human aspects of language may be related to the
      genetics of schizophrenia.

PMID- 11596850
TI  - Disturbed circadian rest-activity cycles in schizophrenia patients: an effect of
      drugs?
AB  - The circadian rest-activity cycle of schizophrenia patients stabilized for more
      than a year on monotherapy with a "classical" neuroleptic (haloperidol,
      flupentixol) or with the atypical neuroleptic clozapine was documented by
      continuous activity monitoring for 3-7 weeks. In this pilot study, the three
      patients treated with clozapine had remarkably highly ordered restactivity
      cycles, whereas the four patients on classical neuroleptics had minor to major
      circadian rhythm abnormalities. This is the first documentation of circadian rest
      activity cycle disturbances in schizophrenia related to class of drug.

PMID- 11596851
TI  - Neuroleptic effects on autonomic activity in schizophrenia: between-group and
      within-subject paradigms and comparisons with controls.
AB  - Effects of fluphenazine on electrodermal activity (EDA) and heart rate (HR) were
      studied in patients with schizophrenia and normal control subjects during rest
      periods, presentation of innocuous tones, and a reaction time (RT) task. Two
      types of analyses were used: (1) between-group analyses-patients taking placebo
      were compared with patients taking fluphenazine and with control subjects using
      only data from the first test session; and (2) within-subject analyses-the same
      patients were tested when taking fluphenazine and when taking placebo. Results
      showed higher resting EDA and HR and smaller increments to task performance in
      placebo patients than in control subjects. Fluphenazine attenuated EDA levels but
      not the tonic response. Fluphenazine attenuated the HR response but did not
      affect HR level. Placebo patients were electrodermally hyporesponsive to the RT
      stimuli but not to simple tones. Fluphenazine markedly attenuated responsivity to
      simple tones but it attenuated responsivity less for RT stimuli. Testing
      medicated patients may thus produce misleading results with respect to many, but
      not all, purported autonomic markers of diagnosis in schizophrenia studies.

PMID- 11596852
TI  - Staff expressed emotion and causal attributions for client problems on a low
      security unit: an exploratory study.
AB  - This is an exploratory study that sought to investigate a number of measures of
      staff-patient relationships on a continuing care, low security inpatient facility
      for patients with severe mental illness. Twenty staff members were assessed for
      expressed emotion (EE) using the Camberwell Family Interview (CFI) in regard to a
      client for whom they were a designated key worker. Their spontaneous attributions
      for the patient's problems were also assessed, along with self-report staff and
      patient ratings of their expressed and perceived feelings and thoughts about
      their staff or patient counterpart. The study found that although none of the
      staff were rated as fulfilling criteria for high EE, there was evidence of some
      variability in the quality of staff-patient relationships as assessed from the
      subjective self-report scales of staff and patients. Patients seemed to be
      sensitive to staff feelings for them: patient ratings of perceived feelings and
      thoughts from staff were significantly correlated with staff expressed feelings
      both from the CFI EE ratings and the direct self-report staff measures. Staff
      tended to view the behaviors of patients they felt less positively disposed
      toward as more controllable, and this association between less benign
      explanations of behavior and a more critical attitude is consistent with the
      attribution research for familial caregivers. The more negatively perceived
      patient group was found to be more likely to have behavioral disturbances in the
      7 months after the relationship ratings were made. This article discusses
      measurement issues in the assessment of formal caregiver-patient relationships in
      the light of this and previous studies.

PMID- 11596853
TI  - Longitudinal assessment of negative symptoms in schizophrenia/schizoaffective
      patients, other psychotic patients, and depressed patients.
AB  - This study assessed differences in negative symptom presentation between
      schizophrenia/schizoaffective, other psychotic, and depressed patients over a 10
      year followup period. One hundred fifty individuals with schizophrenia or
      schizoaffective disorders (SZ/SZAF), other psychotic disorders (OP), and
      depressed patients (DP) were assessed at index hospitalization, then reassessed
      at 4.5-year, 7.5-year, and 10-year followups. SZ/SZAF patients significantly
      differed from DP patients in frequency and persistence of negative symptoms but
      were not significantly different from the OP group. Negative symptoms were not
      associated with depression in any diagnostic group. Dosage, but not simple use,
      of conventional antipsychotic medications was related to severity of symptoms in
      the SZ/SZAF group. Although negative symptoms were typically most severe and most
      common in the SZ/SZAF subjects in comparison to the DP patients, there were few
      statistically significant differences in the phenomenology of negative symptoms
      between the OP and SZ/SZAF groups. The data are consistent with a model that
      identifies negative symptoms as common to mental illnesses generally, with
      particularly high rates in psychotic illnesses.

PMID- 11596854
TI  - A psychiatric resident's journey through the closed ward.

PMID- 11596855
TI  - Polyamines and cell migration.
AB  - Leeuwenhoek first described polyamines in 1677, but active investigation did not
      begin until the 1970's. When intracellular polyamine levels are reduced by
      inhibitors, mutation, or transfection, severe reductions occur in cell division,
      cell differentiation, and cell migration. These effects are not difficult to
      demonstrate and measure, and all can be prevented if supplemental exogenous
      polyamines are supplied. However, linking the overall effects to molecular events
      remains to be accomplished. In this review, we discuss work (mostly from the last
      10 years) that relates to cell migration. Specifically, we have discussed the
      biology and biochemistry of the polyamines, their transport and regulation, the
      structure of the cytoskeleton and the mechanics of cell movement. We have also
      considered four specific processes that polyamines participate in that may affect
      cell migration significantly. These are: 1) the regulation of intracellular Ca++
      concentration by voltage-gated K+ channels, 2) the maintenance of normal RhoA
      levels that, with Rac, regulate the assembly of actin stress fibers, focal
      adhesions, and contractility, 3) the formation of ATP-Mg++-polyamine trimers that
      enhance the phosphorylation activity of ATP toward enzymes in specific signaling
      pathways and, 4) alterations in the structure of RNA that change translation
      initiation sites and affect the expression of proteins.

PMID- 11596856
TI  - Guanylin and related peptides.
AB  - Guanylin and uroguanylin are short peptides homologous to heat-stable
      enterotoxins of Escherichia coli and other enteric bacteria. Guanylin and
      uroguanylin are synthetized from the respective prepropeptides mainly in
      gastrointestinal mucosa and are secreted both into intestinal lumen and into the
      blood. Luminally secreted peptides stimulate chloride and bicarbonate secretion
      in the intestine through the mechanism involving guanylate cyclase C receptor,
      cyclic GMP, protein kinase G and cystic fibrosis transmembrane conductance
      regulator (CFTR) chloride channel. Bacterial enterotoxins, which have greater
      potency than endogenous peptides, induce excessive fluid secretion into
      intestinal lumen leading to secretory diarhea. Uroguanylin is expressed mainly in
      enterochromaffin cells of duodenum and proximal small intestine whereas guanylin
      is abundant in goblet cells of colonic epithelium. Uroguanylin and guanylin
      increase urinary sodium and potassium excretion both as circulating hormones and
      as paracrine mediators produced within the kidney. Uroguanylin functions as
      "intestinal natriuretic hormone" which is secreted in response to oral sodium
      loading and maintains sodium balance during postprandial period. Plasma and
      urinary concentrations of guanylin and uroguanylin increase in renal failure and
      heart failure. Guanylin peptides possess antiproliferative activity in intestinal
      cells culture and their expression decreases in colonic carcinoma indicating that
      their deficiency may contribute to the pathogenesis of this disease.

PMID- 11596857
TI  - Effect of local injection with basic fibroblast growth factor (BFGF) and
      neutralizing antibody to BFGF on gastric ulcer healing, gastric secretion,
      angiogenesis and gastric blood flow.
AB  - Exogenous administration of bFGF was shown to accelerate tissue repair
      predominantly due to an increase in the formation of new microvessels
      (angiogenesis) suggesting that bFGF plays an important role in healing of gastric
      ulcer. This study was designed: 1) to examine the effect of local application of
      bFGF with or without neutralizing antibody (NA) to bFGF and 2) to determine the
      role of gastric secretion, gastric blood flow (GBF) at the ulcer margin and
      angiogenesis during gastric ulcer healing with or without local application of
      NA, bFGF or the combination of NA and bFGF. Chronic gastric ulcers were induced
      in Wistar rats by subserosal application of acetic acid (ulcer area 28 mm2) and
      gastric secretion during ulcer healing was assessed using animals additionally
      equipped with chronic gastric fistulas. The bFGF without or with NA to bFGF (10
      ng/100 microl]), irrelevant antibodies (rabbit IgG; 10 microg/100 microl) or
      vehicle (saline) were locally injected into the subserosa immediately upon ulcer
      induction (day 0) and at day 2. Rats with acetic acid ulcers without subserosal
      injections served as controls. At day 11, all animals were anaesthetized and GBF
      was determined at the ulcer base, ulcer margin as well as in intact mucosa using
      the H2-gas clearance technique and the area of gastric ulcers was measured by
      planimetry. Gastric mucosa with ulcer was excised and the percentage of area
      covered with blood vessels, the number of fibroblasts and the percentage of
      connective tissue at the ulcer edge was assessed by histology. The gastric ulcers
      were healed spontaneously in control vehicle-treated rats at day 11 and this was
      accompanied by the significant increase in the GBF and number of microvessels in
      the ulcer area. The gastric secretion was suppressed immediately after ulcer
      induction and increased significantly at day 2 and day 11 but failed to return to
      that recorded in intact animals. In contrast, local application of bFGF inhibited
      gastric acid and pepsin outputs at each study time intervals tested and this
      effect was reversed by addition of NA to bFGF. Locally applied bFGF accelerated
      significantly ulcer healing and this was accompanied by the greater rise in the
      GBF of ulcer margin and more marked increase in number of microvessels as
      compared to those in vehicle-treated rats. Subserosal application of NA to bFGF
      prolonged significantly the ulcer healing and this effect was accompanied by a
      significant fall in the GBF at the ulcer margin and a decrease in number of
      capillaries in ulcer bed without significant alteration in gastric acid and
      pepsin outputs. The ulcer healing effect of bFGF and accompanying increase in the
      GBF at ulcer margin and in thenumber of microvessels as well as inhibition of
      gastric acid secretion evoked by bFGF were significantly attenuated by the
      addition of NA to bFGF. The number of fibroblasts and the distribution of
      connective tissue did not differ between groups studied. We conclude that; 1)
      depletion of endogenous bFGF at the ulcer area by specific NA to bFGF delays
      healing of gastric ulcers, reduces angiogenesis of ulcer bed and impairs the
      microcirculatory effect of this growth factor at the ulcer margin indicating that
      the availability of bFGF in the ulcer area plays a crucial role in the ulcer
      healing through induction of angiogenesis; 2) this prominent antiulcer effect of
      locally applied bFGF depends, at least in part, upon the inhibition of acid
      secretion by this peptide.

PMID- 11596858
TI  - Involvement of heat shock proteins in the healing of acetic acid-induced gastric
      ulcers in rats.
AB  - The present study examined the expression of 73-kDa of heat shock cognate protein
      (HSC70), 72-kDa of heat shock protein (HSP70) and 47-kDa of HSP (HSP47) observed
      in the ulcer healing process in rats. Gastric ulcers were induced by a luminal
      application of acetic acid in male Donryu rats. During the ulcer healing process,
      the expression of HSPs in the ulcerated tissue was determined. A high level of
      HSC70 expression was observed both in the normal mucosa and ulcerated tissue, but
      the level did not change upon ulceration and ulcer healing. While HSP70 and HSP47
      were markedly expressed in the ulcer base during ulceration, and decreased with
      ulcer healing. HSP70 expression in the ulcer margin was gradually increased with
      ulcer healing. Omeprazole accelerated the healing of gastric ulcers with strong
      inhibition of gastric acid secretion, while indomethactin delayed in ulcer
      healing despite slight inhibition of gastric acid secretion. Omperazole enhanced
      the expression of HSP70 both in the ulcer margin and base, but it reduced HSP47
      expression in the ulcer base Indomethacin markedly enhanced HSP47 expression only
      in the ulcer base. In conclusion, the expression of HSP70 and HSP47 is changed
      during ulcer healing. Furthermore, it was suggested that the enhanced expression
      of HSP70 is involved in acceleration of ulcer healing, but overexpression of
      HSP47 is involved in delayed ulcer healing.

PMID- 11596859
TI  - Histamine in stress ulcer prophylaxis in rats.
AB  - BACKGROUND: Gastrin and its analogues increase the gastric acid secretion, but
      also enhance mucosal defense mechanisms. On the other hand, increased formation
      of histamine leading to an increase in gastric acid secretion is accompanied with
      gastroprotection and acceleration of gastric ulcer healing. AIM: Of this study
      was to examine the effect of histamine on stress induced gastric ulcers in rats.
      METHODS: Male Wistar rats were exposed to water immersion and restrain stress
      (WRS) for 3.5 h at 23 degrees C. Before WRS rats were pretreated with saline,
      histamine, ranitidine or omeprazole. RESULTS: WRS produces gastric lesions which
      were strongly reduced by ranitidine or omeprazole. Also treatment with histamine
      markedly reduced ulcer area evoked by WRS. Addition of histamine to ranitidine or
      omeprazole caused an additional reduction in ulcer area. Gastroprotective effect
      of histamine was accompanied with the increase in gastric blood flow (GBF).
      Administration of omeprazole or ranitidine alone was without significant effect
      on GBF. Histamine caused an slight decrease in gastric luminal pH, whereas
      ranitidine or omeprazole significantly increased gastric luminal pH. Plasma
      interleukin-1beta was significantly reduced after administration of omeprazole,
      ranitidine, or histamine, however, the effect of histamine was less pronounced.
      DNA synthesis was increased after administration of omeprazole, ranitidine or
      histamine when compared with WRS alone. Administration of histamine in
      combination with ranitidine or omeprazole caused an additional increase in DNA
      synthesis. CONCLUSIONS: Histamine exhibits protective effect and increases
      gastroprotective effect of ranitidine and omeprazole against stress-induced
      gastric lesions. This effect of histamine seems to be independent on gastric acid
      secretion but related to the increase in gastric blood flow and the reduction in
      activation of cytokine cascade.

PMID- 11596860
TI  - Responses of the red nucleus neurons to stimulation of the paw pads of forelimbs
      before and after cerebellar lesions.
AB  - Cerebellar cortex ablation releases deep cerebellar nuclei of monosynaptic
      inhibition from Purkinje cells. Therefore, it strengthens excitatory influence
      from Interpositus Nucleus (IN) upon Red Nucleus (RN), which results in much
      higher facilitation of the rubro-spinal neurons. This causes a big increase of
      spontaneous discharge rate, and eliminates brakes of discharges from responses
      generated by somatosensory stimuli. These two changes destroy content and timing
      of feedback information flowing through the spino-cerebello-rubro-spinal loop.
      This false bias of the feedback information, very important for fast postural
      adjustment and coordination of ongoing movements executed by central motor
      program, may at least in part be responsible for abnormal motor behavior evoked
      by cerebellar damage. Hemicerebellectomy resulted in dramatically reduced
      spontaneous activity and responses to limb stimulation because of severing a
      major input to the red nucleus from deep cerebellar nuclei. Due to direct
      somatosensory input to magnocellular Red Nucleus (mcRN) from the spinal cord that
      bypassed the cerebellum, the latency of response to limb stimulation was not
      changed and the narrower receptive fields were still present.

PMID- 11596861
TI  - Effects of 17-beta estradiol and estriol on NMDA-induced toxicity and apoptosis
      in primary cultures of rat cortical neurons.
AB  - Estrogens possess neuroprotective and antiapoptotic properties, however, the
      issue of involvement of estrogen receptors (ER)-dependent genomic pathway in
      these effects still remains controversial. Moreover, the majority of data on
      antiapoptotic effects of estrogens concern non-neuronal cells. In the present
      study we compared effects of the potent ER agonist, estradiol-17beta (E2), and
      its metabolite with a weak affinity for ER, estriol, on the neurotoxicity induced
      by high (1 and 5 mM) NMDA concentrations and on the apoptosis induced by low (0.1
      mM) concentration of NMDA in rat primary cortical neurons. The obtained data
      showed that 24-hour exposure of cortical neurons to NMDA (0.1-5 mM) resulted in a
      dose-dependent increase in LDH level. Twenty four-hour pretreatment with estriol
      (100 nM and 500 nM) reduced the NMDA (1 and 5 mM)-induced toxicity by 16-26%,
      while estradiol-17beta (500 nM) reduced NMDA (5 mM)- induced toxicity by 14%.
      Twenty four hour exposure of cortical neurons to NMDA (0.1 mM) resulted in
      decrease of the level of antiapoptotic protein - Bcl-2 by 60% and increased the
      number of apoptotic cells by 50% compared to the control. Twenty four hour
      pretreatment with estradiol-17beta or estriol (100 and 1000 nM) prevented the
      NMDA-induced apoptotic changes. The specific estrogen receptor antagonist ICI
      182,780 (100 nM) had no effect alone and did not antagonize the effects of
      estrogens on NMDA-induced toxicity as well as on changes in Bcl-2 level. The
      higher efficacy of estriol, together with the fact that the specific ER receptor
      antagonist, ICI 182,780, did not inhibit the above-described effects support the
      hypothesis about a nongenomic mechanism of the anti-NMDA action of estrogens.

PMID- 11596862
TI  - Haematological, blood gas and acid-base effects of central histamine-induced
      reversal of critical haemorrhagic hypotension in rats.
AB  - In a rat model of volume-controlled irreversible haemorrhagic shock, which
      results in a severe metabolic acidosis and the death of all control animals
      within 30 min., intracerebroventricular injection of histamine (100 nmol)
      produces a prompt and long-lasting increase in mean arterial pressure and heart
      rate, with a 100% survival of 2 h after treatment. Histamine action is
      accompanied by a decrease in haematocrit value, haemoglobin concentration,
      erythrocyte and platelet count, and an increase in residual blood volume at the
      end of the experiment (2 h). Cardiovascular effects are also associated with a
      long-lasting rise in respiratory rate and biphasic blood acid-base changes -
      initial increase of metabolic acidosis with the decrease in arterial and venous
      pH, bicarbonate concentration and base excess, followed by almost a complete
      recovery of blood gas and acid-base parameters to the pre-bleeding values, with
      normalisation of arterial and venous pH, Pco2 bicarbonate concentration and base
      excess at the end of experiment. It can be concluded that in the late phase of
      central histamine-induced reversal of haemorrhagic hypotension there is almost a
      complete restoration of blood gas and acid-base status due to circulatory and
      respiratory compensations, while accompanying haematological changes are the
      result of the haemodilution and the increase in residual blood volume.

PMID- 11596863
TI  - Agonist of dihydropyridine receptors, BayK8644 depresses excitation-contraction
      coupling in myocytes of guinea pig heart.
AB  - BayK8644(-)(BayK), an agonist of L-type Ca2+ channels has been recently shown to
      impair excitation-contraction coupling in cardiac myocytes by increasing Ca2+
      leak from the sarcoplasmic reticulum (SR) and by decreasing the gain factor of
      calcium induced release of calcium. It has been proposed that BayK affects the
      properties of ryanodine receptors (RyRs) of SR by binding to the sarcolemmal
      dihydropyridine receptors (DHPRs). This would suggest that the linkage between
      these receptors is more direct than currently sought. However, it has been
      recently found that BayK may also directly affect the RyRs increasing their open
      probability. In this paper we tested the effect of BayK on excitation-contraction
      coupling in single ventricular myocytes of guinea-pig heart superfused with 5 mM
      Ni2+ which blocks the L-type Ca2+ current and Na+/Ca2+ exchange. We have
      previously shown that it is possible to activate in these cells nearly normal
      Ca2+ transients and contractions despite total inhibition of ICa. This eliminated
      the effect of ICa increased by BayK on excitation contraction coupling thus
      simplifying the studied system. 0.5 microM BayK increased the diastolic [Ca2+]i
      and decreased the diastolic length in stimulated or rested cells superfused with
      Ni2+, decreased by approximately 50% amplitude of Ca2+ transients and
      contractions and decreased by approximately 70% the responses of cells to rapid
      superfusion of 15mM caffeine used as an indirect index of the SR Ca2+ content.
      The effects on diastolic length and [Ca2+]i in rested cells were not affected by
      20 microM nifedipine. We conclude that under our experimental conditions the
      dominating mechanism of suppression of excitation-contraction coupling by BayK
      was depletion of the SR Ca2+ by the direct effect on the RyRs.

PMID- 11596864
TI  - On the role of serotonin2A/2C receptors in the sensitization to cocaine.
AB  - Apart from showing involvement of dopamine, recent studies also indicate a role
      of serotonin (5-HT) in the behavioral effects of cocaine in rodents. In the
      present study we investigated the role of 5-HT2A/2C receptors in the development
      or expression of sensitization to cocaine in rats, using ketanserin, an
      antagonist at these receptors. Since ketanserin also shows a high affinity for
      alpha1-adrenoceptors, prazosin, a comparative antagonist at those receptors was
      also examined. Male Wistar rats were treated repeatedly (for 5 days) with cocaine
      (10 mg/kg) in combination with either vehicle, or ketanserin (1-3 mg/kg) or
      prazosin (3 mg/kg); afterwards, on day 10, they received a challenge dose of
      cocaine (10 mg/kg). In another experiment, the animals were given either with
      vehicle or cocaine (10 mg/kg) for 5 days, and were then challenged with cocaine
      (10 mg/kg) in combination with vehicle, or ketanserin (1-3 mg/kg) or prazosin (3
      mg/kg) on day 10. Acute administration of cocaine increased the locomotor
      activity in rats; that hyperactivation was inhibited by ketanserin (3 mg/kg), but
      not by prazosin. In animals treated repeatedly with cocaine, the locomotor
      hyperactivity induced by a challenge dose of the psychostimulant was ca. 2-3
      times higher than that after its first administration. No difference was observed
      in the response to cocaine challenge in rats treated repeatedly with cocaine,
      ketanserin+cocaine, or prazosin+cocaine. In animals treated repeatedly with the
      psychostimulant, the behavioral response to a challenge dose of cocaine was dose
      dependently decreased when the drug was combined with ketanserin, but not with
      prazosin. The above findings indicate a role of 5-HT2A/2C receptors (but not
      alpha1-adrenoceptors) in the acute locomotor hyperactivity, as well as in the
      expression (but not development) of cocaine sensitization. Since chronic use of
      cocaine by humans may lead to psychoses or craving for this drug of abuse, our
      findings also seem to indicate possible importance of 5-HT2A/2C receptor
      antagonists in the therapy of cocaine addiction.

PMID- 11596865
TI  - Intracellular reduced glutathione content in normal and type 2 diabetic
      erythrocytes: effect of insulin and (-)epicatechin.
AB  - Catechins, polyphenolic compounds belonging to flavanoid family, have been
      reported to posses insulin-like properties and their antidiabetic actions have
      also been documented. Recently catechins have received much attention as strong
      anti-oxidative agents. Since oxidative stress has been implicated in the
      development of diabetic complications and GSH plays an important role in
      protection against oxidative damages, we have studied the in vitro effect of (
      )epicatechin and insulin on the reduced glutathione content in normal and type 2
      diabetic erythrocytes. The GSH content was significantly lower (p < 0.001) in
      type 2 diabetic patients as compared to normal individuals. In vitro insulin
      treatment (10(-9) M) resulted in increase in the GSH content in both normal and
      type 2 diabetic erythrocytes. (-)Epicatechin (1mM) also resulted in an increase
      in erythrocyte GSH content in both normal and type 2 diabetic erythrocytes.
      Insulin gave a pronounced dose-responsive effect: maximum increase in GSH content
      at physiological hormone concentration and a lower increase at higher and lower
      insulin concentrations. (-)Epicatechin did not show a similar dose-responsive
      effect. Although the exact mechanism by which (-)epicatechin causes elevation of
      erythrocyte GSH is not clear nevertheless this finding may have important
      therapeutic implications. A higher content of dietary flavanoids may thus protect
      diabetic patients against long-term complications.

PMID- 11596866
TI  - The involvement of GABA(A) receptors in the control of GnRH and beta-endorphin
      release, and catecholaminergic activity in the ventromedial-infundibular region
      of hypothalamus in anestrous ewes.
AB  - To examine the role of the GABA(A) receptor mediating systems in the control of
      gonadotropin-releasing hormone (GnRH) release from the ventromedial-infundibular
      region (VEN/IN) of anestrous ewes, the extracellular concentrations of GnRH, beta
      endorphin, noradrenaline (NE), dopamine (DA), 4-hydroxy-3-methoxy-phenylglycol
      (MHPG) and 3,4-dihydroxy-phenylacetic acid (DOPAC) were quantified during local
      stimulation or blockade of GABA(A) receptors with muscimol or bicuculline
      respectively. In most animals stimulation of GABA(A) receptors significantly
      attenuates GnRH release with concomitant increase of beta-endorphin and DA
      release, and MHPG and DOPAC levels. Blockade of the GABA(A) receptors generally
      did not affect GnRH and NE release but inhibited in most animals beta-endorphin
      release and decreased dopaminergic activity. These results suggest, that GABA may
      suppress GnRH release directly by GABA(A) receptor mechanism on the axon terminal
      of GnRH neurons or indirectly by GABA(A) receptor processes activating beta
      endorphin-ergic and dopaminergic neurons in the VEN/NI. On the basis of these
      results in could not be distinguish between these two events. The decrease in
      extracellular beta-endorphin and dopamine concentration without evident changes
      in the GnRH level during GABA(A) receptor blockade may suggest that other
      neuronal systems are involved in this effect.

PMID- 11596867
TI  - Uterine nitric oxide and prostaglandin E during embryonic implantation in non
      insulin-dependent diabetic rats.
AB  - In the process of embryo implantation in the rat, both nitric oxide and
      prostaglandins act as vascular and myometrial regulators. The aim of the present
      work was to evaluate the effect of diabetes on the synthesis of both agents
      during embryo implantation. In diabetic rats, uterine activity of the enzyme
      nitric oxide synthase and prostaglandin E production were increased during peri
      implantation compared to the control group (P < 0.05 and P < 0.001,
      respectively). Both parameters showed a prolonged increase in temporal profile
      during peri-implantation days. Local production of nitric oxide and prostaglandin
      E in the implantation sites was higher in diabetic rats (P < 0.05), but the
      intersite:site ratio was similar to that of the control group. On the other hand,
      the implantation rate and the timing of the beginning of this process were not
      altered in the diabetic group. These results suggest that the vasoactive
      modulators of the implantation process, nitric oxide and prostaglandins, are
      increased in this diabetic pathology, and that this increase is probably
      functioning as a compensatory mechanism, so as to allow an unaltered rate of
      embryo implantation in this model.

PMID- 11596868
TI  - Construction and immunological assessment of Salmonella typhimurium expressing
      fox sperm LDH-C4.
AB  - This study examined immune responses of foxes to oral doses of recombinant
      Salmonella typhimurium expressing fox sperm-specific lactate dehydrogenase
      (fLDH). The cDNA for fLDH was cloned into the expression plasmid pKK233.2
      (pKKfLDH). Salmonella typhimurium aroA- (SL3261) was transformed with either the
      pKK233.2 plasmid alone (SpKK) or the pKKfLDH construct (SpKfLDH). The fLDH
      expressed by SpKfLDH retained enzymatic activity and was recognized by human LDH
      C4-specific antibody. Male European red foxes (Vulpes vulpes) were given an
      initial oral dose of 1 x 10(11) cfu of either SpKK (control, n = 3) or SpKfLDH
      (test, n = 6), followed four weeks later with a further dose of 1 x 10(11) cfu.
      Antibodies to Salmonella lipopolysaccharide (LPS-04) and fLDH were measured in
      plasma and saliva for eight consecutive weeks after the initial doses. Both LPS
      04 IgG- and IgA-specific antibodies as well as fLDH-specific IgG antibodies were
      detected in plasma and saliva. However, there was a marked fLDH-specific IgA
      response in saliva consistent with induction of the common mucosal immune system.
      The antibody measurements demonstrated the feasibility of using recombinant
      Salmonella as an oral vaccine to elicit gamete antigen-specific mucosal immune
      responses in foxes.

PMID- 11596869
TI  - Ontogeny of pro-opiomelanocortin (POMC) gene expression and translated products
      adrenocorticotrophin (ACTH) and alpha-melanocyte stimulating hormone (alpha-MSH)
      in the ovine fetal pituitary gland.
AB  - This study sought to determine the ontogeny of pro-opiomelanocortin (POMC) mRNA
      by in situ hybridization, and the expression of alpha-melanocyte stimulating
      hormone (alpha-MSH) and adrenocorticotrophin (ACTH) by immunohistochemistry, in
      the ovine fetal pituitary gland. Detection of POMC mRNA, and of ACTH and alpha
      MSH immunoreactivity was first noted at Day 40 of gestation in the pars
      intermedia (PI) and the pars distalis (PD). After Day 70, alpha-MSH
      immunoreactivity was confined to the PI whereas POMC mRNA and ACTH immunostaining
      remained in both the PI and the PD. Increases (P < 0.05) of POMC mRNA expression
      were observed in the PI between Days 50-70 and levels then remained constant to
      Day 141 (term, 145 days). In the basal region of the PD, POMC mRNA expression was
      high at Day 40, declined (P < 0.01) by Day 50 and then increased progressively to
      Day 141 of gestation. The proportion of ACTH-immunopositive cells in the PD also
      fell from 14% at Day 40 to 11.4% at Day 70 and then increased to 15.3% by Day
      141. In contrast, neither the level of POMC mRNA expression nor the percentage of
      corticotrophs changed in the region of the PD immediately adjacent to the PI.
      These data provide evidence for differential processing of POMC in a tissue
      specific manner during early fetal pituitary development.

PMID- 11596870
TI  - Oestrogen regulation of insulin-like growth factor binding protein-3 (IGFBP-3)
      and expression of IGFBP-3 messenger RNA in the ovine endometrium.
AB  - Transcriptional regulation of insulin-like growth factor binding protein-3 (IGFBP
      3) by oestrogen was investigated by Northern blot hybridization of endometrial
      tissue mRNA from anoestrous ewes treated with oestradiol-17beta at either 0, 40
      or 80 microg per day for 7 days. The 2.6 kb IGFBP-3 transcript, seen in control
      animals, was virtually undetectable in treated animals. This suppressive effect
      was reflected in Western ligand blots of the uterine luminal fluid (ULF) proteins
      where the concentration of IGFBP-3 was significantly decreased with increasing
      oestrogen treatments. IGFBP-2 levels were increased with oestradiol treatment but
      no significant effect was seen on the other minor IGFBP's present in the ULF.
      Northern analysis also showed that the IGFBP-3 transcript was present from days
      12 to 16 of the oestrous cycle but was either absent or very weak on days 0
      (oestrus) and 9 of cycling ewes. In situ hybridization of endometrial tissue
      sections localized the IGFBP-3 mRNA to the luminal epithelial cell layer, areas
      of the stromal tissue and in some glandular epithelial cells. Oestradiol
      treatment of ewes down-regulated expression of IGFBP-3 in the endometrium;
      therefore, the low levels of IGFBP-3 in ULF during the early part of the oestrous
      cycle is possibly due to elevated levels of plasma oestradiol around oestrus.

PMID- 11596871
TI  - Control of endometrial phosphoinositide hydrolysis and prostaglandin F2alpha
      secretion in pigs.
AB  - This study examined the control of endometrial phosphoinositide (PI) hydrolysis
      and prostaglandin (PG) F2alpha release by oxytocin (OT) and vasopressin in cyclic
      pigs on Day 15 post oestrus. In Expt 1, OT and arginine-vasopressin (AVP)
      increased endometrial PI hydrolysis (P<0.01), but only OT stimulated (P<0.01)
      PGF2alpha secretion. In Expt 2, OT and lysine-vasopressin (LVP) increased PI
      hydrolysis (P<0.01). No difference was detected between the 100 nM and 200 nM
      concentrations of OT or between the 100 nM and 200 nM concentrations of LVP. The
      increase in PI hydrolysis was greater (P<0.05) for 100 nM OT plus 100 nM LVP than
      for the 100 or 200 nM concentrations of OT or LVP alone. In Expt 3, OT (P<0.01)
      and LVP increased (P<0.01) PI hydrolysis. An OT antagonist abolished (P<0.01) the
      OT-induced increase in PI hydrolysis, but did not significantly alter the LVP
      induced increase. A type 2 VP antagonist completely inhibited (P<0.01) the LVP
      induced increase in PI hydrolysis, but only partially antagonized the stimulatory
      effect of OT (P<0.01). These results are consistent with the proposal that OT
      acts through specific receptors to promote endometrial PGF2alpha secretion in
      pigs.

PMID- 11596872
TI  - Maternal nicotine exposure during gestation and lactation interferes with
      alveolar development in the neonatal lung.
AB  - The aim of this study was to investigate the effect of maternal nicotine exposure
      during pregnancy and lactation on the development of the lungs of the offspring
      as a gas-exchanger. Pregnant rats received nicotine (1 mg/kg body mass day(-1))
      subcutaneously during gestation and lactation. Nicotine administration started
      one day after mating and lasted until weaning on post natal Day 21. The offspring
      were exposed to nicotine only via the placenta and the milk of the mother. The
      lung tissue of the neonates was collected on post natal Days 14, 21, 35 and 42
      and prepared for morphometry. The results obtained show that maternal nicotine
      exposure suppressed alveolarisation in the lungs of the offspring, which resulted
      in a reduced internal surface area available for gas exchange. The radial
      alveolar count as well as the number of capillaries in the septa were also
      significantly lower than in the control animals. It is concluded that maternal
      nicotine exposure had an adverse effect on the development of the gas exchange
      region of the lungs of the offspring that persisted at least up to Day 42 after
      birth.

PMID- 11596873
TI  - Fetal growth and development following temporary exposure of day 3 ovine embryos
      to an advanced uterine environment.
AB  - The effect of exposing Day 3 ovine embryos to an advanced uterine environment for
      a period of 3 days on subsequent fetal growth and development between Day 35 and
      Day 135 of gestation was studied. Day 3 embryos were recovered from superovulated
      donor ewes and transferred to synchronous final or asynchronous temporary
      recipients for 3 days. Embryos were recovered from these temporary recipients and
      transferred to Day 6 final recipients. Gravid uteri were recovered, weighed and
      dissected on Days 35, 45, 60, 90, 110, 125 and 135 of gestation. Fetal weight and
      length data were analysed by fitting non-linear Gompertz models of the form
      log(e) y = a - be(-ct), where y is fetal size and t is time from conception.
      Various terms including treatment, gestational age, embryo stage at transfer and
      fetal sex were fitted to this model. Fetal development was assessed by relating
      organ weight to fetal bodyweight using the linear allometric equation log(e) y =
      log(e) a + b log(e) x, where y is organ weight and x is fetal weight. Temporary
      exposure of Day 3 embryos to an advanced uterine environment did not increase the
      rate of embryo development and had no effect on fetal growth and development
      between Days 35 and 135 of gestation in this study. A single Gompertz model
      (log(e) y = 10.134 - 17.047e(-0.1733t)) explained 99.8% of the variation in fetal
      weight. Of terms fitted to this model only gestational age and fetal sex
      influenced fetal weight, with male fetuses being 5% heavier (P<0.05) than female
      fetuses. Fetal development was also unaffected by experimental treatment in this
      study. Allometric coefficients established for various fetal components agreed
      well with those from previously published studies.

PMID- 11596874
TI  - Pre- and post-natal growth of the human ductus epididymidis. A morphometric
      study.
AB  - A histometric study of the development of the human epididymis from the fetal
      period to adulthood has been carried out in males without testicular or related
      pathology, distributed into the following groups: (I) fetuses (between the 28th
      and 37th week of pregnancy); (II) newborns (1-30 days of age); (III) infants (2-4
      months of age); (IV) infants (5-12 months of age); (V) infants (1-4 years of
      age); (VI) children (5-14 years [prepubertal]); and (VII) adults (15-60 years of
      age). For each age group and each epididymal portion (efferent ducts, caput,
      corpus and cauda epididymidis) the parameters measured were (1) total surface
      (epithelium + muscular layer + lumen); (2) the surface occupied by the lumen; (3)
      the surface occupied by the muscular layer; (4) total diameter of the duct; (5)
      total diameter of the lumen; and (6) the height of the epithelium. The results of
      the present study revealed that the development of the efferent ducts and ductus
      epididymidis follows a biphasic pattern. A progressive development occurs from
      the fetal period to infants 2-4-months of age. However, this development is
      transient and regresses during infancy (groups IV and V). At childhood (group
      VI), a definitive development is initiated and completed at puberty (group VII).
      These changes seem to be related to the androgen-dependence of the epididymis,
      the different stages of testicular maturation, and the steroidogenic activity of
      Leydig cells.

PMID- 11596875
TI  - Amino acid metabolism of bovine blastocysts derived from parthenogenetically
      activated or in vitro fertilized oocytes.
AB  - The uptake and synthesis of 19 amino acids by fresh or frozen-thawed bovine
      blastocysts produced by parthenogenesis (PT) or in vitro fertilization (IVF) were
      compared in the present study. Fresh blastocysts, 180 h after IVF or PT
      activation, and frozen-thawed blastocysts, 168 h old and cultured for 12 h post
      thawing, were cultured in synthetic oviduct fluid medium (SOFM) containing
      polyvinyl alcohol (PVA) with both essential and non-essential amino acids (EAA
      and NEAA, respectively) (Medium 1: M1) or SOFM containing PVA with only EAA
      (Medium 2: M2). In Experiment 1, when fresh or frozen-thawed PT blastocysts were
      cultured in M1, the uptake of glutamate (in fresh only), aspartate and arginine,
      and the synthesis of glutamine and alanine were significantly enhanced. In the
      culture with M2, serine, asparagine, glutamate, glutamine, glycine, arginine and
      alanine were significantly taken up. It was found that the glutamine
      concentrations was significantly higher (P < 0.001) in the culture medium drops
      containing embryos than in the drops without embryos. In Experiment 2, when PT
      blastocysts were cultured in M1, the uptake of aspartate and synthesis of alanine
      were greater (P < 0.01) than those by IVF blastocysts. When M2 was used, a
      significant (P < 0.01) production of serine, asparagine, glutamate, glutamine and
      alanine, and the uptake of arginine by PT blastocysts were observed. In
      Experiment 3, when IVF blastocysts were cultured in M1, fresh blastocysts
      depleted more aspartate and glutamate, and produced more glutamine and alanine
      than frozen-thawed blastocysts. When cultured in M2, frozen-thawed blastocysts
      depleted more threonine (P < 0.01) than fresh blastocysts. These results indicate
      that the uptake and synthesis of amino acids were different in fresh or frozen
      thawed bovine blastocysts derived from PT or IVF. These differences in amino acid
      metabolism may be related to the viability of the blastocysts.

PMID- 11596876
TI  - Cloning of the red kangaroo (Macropus rufus) follicle stimulating hormone beta
      subunit.
AB  - The cDNA encoding the follicle stimulating hormone beta subunit (FSH-beta) was
      isolated from a red kangaroo pituitary cDNA library by using a porcine probe and
      the nucleotide sequence for the coding region was determined. The highest degree
      of deduced amino acid sequence identity (91%) was observed between the red
      kangaroo and another marsupial, the brushtail possum (Trichosurus vulpecula),
      followed by eutherian species (76%, 75% and 74%, respectively, for pig, mouse and
      sheep). Based on the deduced red kangaroo FSH-beta amino acid sequence, putative
      antigenic sites have been identified that may prove useful for studying the
      hormonal control of reproduction in marsupials.

PMID- 11596877
TI  - Differential expression of activin subunits, activin receptors and follistatin
      genes in bovine oocytes and preimplantation embryos.
AB  - The presence of inhibin subunits (alpha, betaA and betaB), activin binding
      protein follistatin and activin receptors (ActR-I, ActR-IB, ActR-II and ActR-IIB)
      mRNA transcripts in bovine oocytes and preimplantation embryos was examined by
      reverse transcription-polymerase chain reaction. Immature and matured oocytes,
      zygotes, 2-cell, 3-4-cell, 5-8-cell, 9-16-cell embryos, morulae, blastocysts and
      hatched blastocysts were produced by in vitro maturation, fertilization and
      culture for this study. Activin betaA subunit and follistatin transcripts were
      detected in all of the stages tested. However, alpha subunit transcripts were
      detected only in oocytes (immature and matured), blastocysts and hatched
      blastocysts, and no betaB subunit transcripts were found in any of the stages.
      Whereas ActR-I transcripts were detectable in all stages, ActR-IB transcripts
      were not detectable in oocytes or embryos except in matured oocytes. Activin type
      II receptors (ActR-II and ActR-IIB) transcripts were detectable in oocytes and
      embryos except for ActR-IIB, which was not found in the 5-8-cell stage embryos.
      The results suggest that bovine embryos may produce activin A (homodimer of the
      betaA subunits) at least from zygotes to morulae. Furthermore, bovine oocytes and
      embryos express the activin receptors mainly by the combination of ActR-I and
      either ActR-II or ActR-IIB.

PMID- 11596878
TI  - Anthrax toxin.
AB  - Anthrax is primarily a disease of herbivores caused by gram-positive, aerobic,
      spore-forming Bacillus anthracis. Humans are accidental hosts through the food of
      animal origin and animal products. Anthrax is prevelant in most parts of the
      globe, and cases of anthrax have been reported from almost every country. Three
      forms of the disease have been recognized: cutaneous (through skin),
      gastrointestinal (through alimentary tract), and pulmonary (by inhalation of
      spores). The major virulence factors of Bacillus anthracis are a poly-D glutamic
      acid capsule and a three-component protein exotoxin. The genes coding for the
      toxin and the enzymes responsible for capsule production are carried on plasmid
      pXO1 and pXO2, respectively. The three proteins of the exotoxin are protective
      antigen (PA, 83 kDa), lethal factor (LF, 90 kDa), and edema factor (EF, 89 kDa).
      The toxins follow the A-B model with PA being the B moeity and LF/EF, the
      alternative A moeities. LF and EF are individually nontoxic, but in combination
      with PA form two toxins causing different pathogenic responses in animals and
      cultured cells. PA + LF forms the lethal toxin and PA + EF forms the edema toxin.
      During the process of intoxication, PA binds to the cell surface receptor and is
      cleaved at the sequence RKKR (167) by cell surface proteases such as furin
      generating a cell-bound, C-terminal 63 kDa protein (PA63). PA63 possesses a
      binding site to which LF or EF bind with high affinity. The complex is then
      internalized by receptor-mediated endocytosis. Acidification of the vesicle leads
      to instertion of PA63 into the endosomal membrane and translocation of LF/EF
      across the bilayer into the cytosol where they exert their toxic effects. EF has
      a calcium- and calmodulin-dependent adenylate cyclase activity. Recent reports
      indicate that LF is a protease that cleaves the amino terminus of mitogen
      activated protein kinase kinases 1 and 2 (MAPKK1 and 2), and this cleavage
      inactivates MAPKK1 and thus inhibits the mitogen-activated protein kinase signal
      transduction pathway. We describe in detail the studies so far done on unraveling
      the molecular mechanisms of pathogenesis of Bacillus anthracis.

PMID- 11596879
TI  - Chromobacterium violaceum: a review of pharmacological and industiral
      perspectives.
AB  - Violet-pigmented bacteria, which have been described since the end of the 19th
      century, are occasionally the causative agent of septicemia and sometimes cause
      fatal infection in human and animals. Bacteria, producing violet colonies due to
      the production of a nondiffusible pigment violacein, were classified as a
      redefined genus Chromobacterium. Chromobacterium violaceum is gram-negative, and
      saprophyte from soil and water is normally considered nonpathogenic to human, but
      is an opportunistic pathogen of extreme virulence for human and animals. The
      biosynthesis and biological activities of violacein and the diverse effects of
      this pigment have been studied. Besides violacein, C. violaceum produces other
      antibiotics, such as aerocyanidin and aerocavin, which exhibit in vitro activity
      against both gram-negative and gram-positive bacteria. 3,6-Dihydroxyindoxazene
      and Y-TO678h exhibit a selective activity against gram-negative bacteria.
      Arphamenine A and B, and FR901228, that enhanced immunoresponse, and potentiators
      of beta-lactam antibiotics and chelators such as ferrioxamine exhibit important
      clinical potential applications. Lipopolysaccharides and polyhydroxyesters
      together with several enzymes appear as important metabolites with
      biotechnological applications. Many of these metabolites were already studied at
      the genome level.

PMID- 11596880
TI  - Can synchronous cultures of bacteria be manufactured?
AB  - The bacterial cell cycle is simpler and different than that of the typical
      eukaryotic cell cycle. The selective pressure during evolution has been directed
      to achieve optimal growth of the individual free-living microbial cell instead of
      a variety of replication rates of the differentiated cell within an entire
      multicellular organism. This means that for most bacterial cells division depends
      more critically on their success in acquiring and using resources than is the
      case for most eukaryotic cells. The further implication is that bacterial cells
      somehow measure their own success in growth and from this 'decide' when they
      should attempt cell cycle events such as cell division and chromosome
      replication. On the assumption that bacterial division is responsive, directly or
      indirectly, to cell size, the cell cycle is analyzed here through Monte Carlo
      simulations. The results are used to consider the possibility of generating
      bacterial cultures growing synchronous. Because the precision of the size-at
      division is surprisingly good, it appears that some organisms, at least, have a
      sensory mechanism that responds to their success in cell growth. It is known that
      the division size of some strains, however, is more precisely regulated than in
      others. Also, some strains are more precise in dividing the mother's cell
      cytoplasm to give the same sized daughters. Because some strains are much more
      precise than others, the possibility is raised that useful synchrony could be
      obtained with selected strains that are precise in these two aspects. These
      cultures would useful in studying other aspect of the physiology of cell growth.

PMID- 11596881
TI  - Treatment of surgical lesions and complications of common bile ducts:
      introduction.

PMID- 11596882
TI  - Biliary strictures: classification based on the principles of surgical treatment.
AB  - The classification of biliary strictures used at Hopital Paul Brousse is based on
      the lowest level at which healthy biliary mucosa is available for anastomosis.
      The classification is intended to help the surgeon choose the appropriate
      technique for the repair. Type I strictures, with a common duct stump longer than
      2 cm, can be repaired without opening the left duct and without lowering the
      hilar plate. Type II strictures, with a stump shorter than 2 cm, require opening
      the left duct for a satisfactory anastomosis. Lowering the hilar plate is not
      always necessary but may improve the exposure. Type III lesions, in which only
      the ceiling of the biliary confluence is intact, require lowering the hilar plate
      and anastomosis on the left ductal system. There is no need to open the right
      duct if the communication between the ducts is wide. With type IV lesions the
      biliary confluence is interrupted and requires either reconstruction or two or
      more anastomoses. Type V lesions are strictures of the hepatic duct associated
      with a stricture on a separate right branch, and the branch must be included in
      the repair. Although this classification is intended for established strictures,
      it is commonly used to describe acute bile duct injuries. The surgeon must be
      aware, however, that the established stricture is generally one level higher than
      the level of the injury at the original operation.

PMID- 11596883
TI  - Surgical management of benign strictures of the biliary tract.
AB  - Benign strictures of the biliary tract are difficult to treat surgical
      complications. Most biliary strictures result from injuries during
      cholecystectomies, and their initial management is a major determining factor of
      the long-term outcome. Only surgeons well trained and experienced in their
      management should treat this entity. The affected patients present various signs
      and symptoms depending on the time the lesion is detected, and the treatment
      modality largely depends on such timing. The success of surgical treatment with
      its attendant low morbidity and mortality makes it the preferred modality over
      transhepatic image-guided or endoscopic balloon dilatation, with or without the
      insertion of stents. Surgical treatment is based on three principles: good
      exposure for internal drainage of the intrahepatic biliary tract, mucosa-to
      mucosa anastomosis, and prevention of the risk of reoperation for recurrent
      stenosis. Roux-en-Y hepaticojejunostomy with a blind subcutaneous jejunal loop
      seems to comply with these three principles. Transanastomotic stents are not
      necessary. We have analyzed our experience from 1988 to 1999 with 65 consecutive
      patients referred to us for biliary reconstruction. We used the Roux-en-Roux-en-Y
      hepaticojejunostomy with a blind subcutaneous jejunal loop, performed by the same
      surgical group in all cases.

PMID- 11596884
TI  - Dilatation of biliary strictures through the afferent limb of a Roux-en-Y
      choledochojejunostomy in patients with sclerosing cholangitis.
AB  - Repeated dilatation of biliary strictures in patients with sclerosing cholangitis
      through a subcutaneously placed afferent limb of a choledochojejunostomy is
      technically feasible and safe. This study is a prospective 15-year evaluation of
      36 patients treated by repeat dilatation through this jejunal limb. There was one
      operative death and one major complication of dilatation. The 5-year survival of
      all patients was 74%. If patients with cirrhosis or unproven cholangiocarcinoma
      at the time of operation are not included, the 5-year survival is 86%. The 15
      year survival of all patients was 30%; it was 64% if those with cirrhosis and
      unproven cholangiocarcinoma at the time of operation are not included. Six
      patients are presently alive with an average survival of 159 months. The study
      suggests that a combination of repeated dilatations combined with transplantation
      is the approach of choice in selected patients.

PMID- 11596885
TI  - Surgical treatment of iatrogenic lesions of the proximal common bile duct.
AB  - Between January 1979 and September 1999 a series of 96 patients were operated on
      at our institution for iatrogenic biliary injuries, and among them 62 involved
      the proximal biliary tract. Injuries, according to the Strasberg classification,
      were type E2 in 18 patients, type E3 in 29 patients, and type E4 in 15 patients.
      The most frequent primary surgical procedures were laparoscopic cholecystectomy
      in 27 of the 62 patients (43.6%) and open cholecystectomy in 30 patients (48.3%).
      Previous repair had been attempted in 25 patients (40.3%). A total of 58
      cholangiojejunostomies were performed. Repair had been performed directly, and a
      T-tube had been left in the main bile duct in four patients with E2 Strasberg
      lesions. Postoperative death occurred in four patients (6.4%). Outcome was graded
      as excellent, good, or poor depending on clinical symptoms, liver function tests,
      and the need for reintervention due to anastomotic stricture. The final outcome
      was evaluated in 54 patients. The mean follow-up was 5.9 +/- 0.3 years, with the
      longest follow-up 10.2 years. Following our first repair 49 of the 54 patients
      (90.7%) had excellent results, 1 (1.9%) had good results, and 4 (7.4%) had poor
      results. None of the patients who underwent immediate or early repair had
      complications. Diagnostic and therapeutic courses are given on the basis of the
      type of lesion and the timing of repair. We emphasize the importance of timing
      (i.e., carrying out surgical repair as soon as possible) and of
      cholangiojejunostomy reconstruction in respect to defined technical principles.
      Moreover, we believe that repair treatment at a hepatobiliary center with
      multidisciplinary competence greatly influences the final long-term outcome.

PMID- 11596886
TI  - Long-term biliary complications after liver surgery leading to liver
      transplantation.
AB  - Chronic biliary obstruction with repeated bouts of cholangitis adversely affects
      quality of life and may lead to secondary biliary cirrhosis with liver failure.
      We reviewed our experience with chronic biliary complications after surgical
      treatment of various diseases that at the end needed a liver transplantation.
      Twelve patients with previous biliary surgery developed secondary biliary
      cholangitis, secondary biliary cirrhosis, or both. Seven had surgery for liver
      hydatid disease by Echinococcus granulosus, another four had complicated biliary
      surgery unrelated to hydatid disease, and one had a history of a traffic accident
      with liver trauma and hepatectomy with chronic biliary fistula. The repeated
      cholangitis attacks and in two cases of hydatid disease the development of
      biliary-bronchial fistulas made these patients' lives miserable. All had had
      previous surgical procedures that made the transplantation procedure more
      difficult. Nevertheless, patient survival and graft actuarial survival after
      liver replacement were 75.0% and 69.2%, respectively, at 5 years.

PMID- 11596887
TI  - Management of biliary duct confluence injuries produced by hepatic hydatidosis.
AB  - From 1978 to 1999 a total of 850 patients underwent surgical treatment for
      hydatid disease of the liver at our surgical department. Biliary duct confluence
      injuries produced by hepatic hydatidosis (HH) were founded in six patients
      (0.7%). Surgical intervention was undertaken to relieve the obstructive jaundice
      and clinical manifestations of cholangitis and to treat the hydatid cyst. A
      partially open cystopericystectomy technique was used in three patients with a
      double bilioenteric Roux-en-Y reconstruction. The remaining three patients (two
      with prehepatic portal hypertension and one with triple hepatic duct confluence)
      were subjected to a cystojejunostomy. There were no hospital deaths. Two cases of
      anastomotic leakage following a high bilioenteric anastomosis occurred but did
      not require surgical treatment. During the follow-up (5-19 years) one patient
      suffered local recurrence of the hydatid disease 7 years after cystojejunostomy.
      The site of intrahepatic biliary and vascular involvement, the presence of
      biliary duct anomalies, and the presence of portal hypertension are decisive
      factors when choosing the "ideal" procedure for reconstruction. Conservative
      surgical approaches (partial cystectomy and cystojejunostomy) are the treatments
      of choice. Radical surgery is often a serious matter.

PMID- 11596888
TI  - Choledocholithiasis: new approach to an old problem.
AB  - The old problem of diagnosis and treatment of choledocholithiasis is analyzed in
      light of recent developments in the field of radiology and surgery. The
      traditional indications for common bile duct (CBD) exploration resulted in a
      large number of unnecessary manipulations of the bile ducts. The same is now true
      of the widespread use of endoscopic retrograde cholangiopancreatography. With the
      advent of magnetic resonance imaging cholangiography, which can clearly
      demonstrate CBD calculi by means of a noninvasive, complication-free technology,
      we should abandon the old indications for CBD exploration and be more
      conservative regarding the diagnosis and management of this condition. In an era
      of minimally invasive surgery we are seeing a significant reduction in the number
      of patients with choledocholithiasis.

PMID- 11596889
TI  - Biliary complications during liver resection.
AB  - Biliary complications after hepatectomy may lead to sepsis, liver failure, and
      death. Measures to detect biliary injury after liver transection may reduce such
      morbidity. The aim of this study was to investigate the trend of biliary
      complications after hepatectomy during the last 10 years and assess the efficacy
      of intraoperative measures (methylene blue test, cholangiography, fibrin glue
      application) for reducing postoperative biliary complications. This is a
      retrospective study of 616 consecutive patients who underwent hepatectomy in our
      institution from January 1989 to September 1998. The study period was divided
      into the first 5 years and the second 5 years for comparison. The hospital
      mortality rate was 6%. It was significantly reduced during the second 5-year
      period (3.3% vs. 10.6%; p = 0.0002). The postoperative biliary leakage rate was
      5.5% and was also reduced during the second 5-year period (3.5% vs. 9.8%; p =
      0.004). Postresection methylene blue tests were performed more frequently during
      the second 5-year period than the first (63% vs. 28%; p = 0.0001). The
      postoperative biliary leakage rate was reduced by the methylene blue test (3.6%
      vs. 7.3%; p < 0.05) but not by application of fibrin glue (7.2% vs. 4.2%) or
      postresection cholangiography. However, among the 60 patients with a positive
      methylene blue test, postoperative biliary leakage still occurred in 10% of them
      after the leakage sites were sutured. In conclusion, the biliary complication
      rate is decreasing. Only the postresection methylene blue test, but not
      postresection cholangiography or application of fibrin glue, helps to reduce the
      postoperative biliary leakage rate.

PMID- 11596890
TI  - Complications of hepatectomy for hilar cholangiocarcinoma.
AB  - We retrospectively reviewed postoperative complications in 105 patients with
      hilar cholangiocarcinoma who underwent hepatectomy at Nagoya University Hospital
      from January 1990 through March 1999. Of the 105 subjects, 97 (92.4%) underwent
      resection of two or more Healey's segments of the liver. Combined portal vein
      resection was performed in 33 (31.4%) patients and pancreatoduodenectomy in 10
      (9.5%). Twenty (19.0%) patients had no postoperative complications, another 39
      (37.1%) patients had minor complication(s) only, and the remaining 46 (43.8%)
      developed major complication(s). The morbidity rate reached as high as 81.0%.
      Major complications required relaparotomy in 11 (10.5%) patients. Of the 46
      patients with major complication(s) 36 recovered; the remaining 10 patients died
      of liver failure with other organ failure(s) or of intraabdominal bleeding 12,
      14, 18, 21, 57, 75, 75, 87, 93, or 134 days after surgery. Thus the 30-day
      mortality was 3.8% and the overall mortality 9.5%. Pleural effusion was the most
      frequent complication found in 66 (62.9%) patients, followed by wound sepsis in
      39 (37.1%), and then liver failure in 29 (27.6%). Liver failure developed in
      16.7% of 48 patients with less than 50% liver resection and in 36.8% of 57
      patients with 50% or more resection (P < 0.05). Other organ failures, including
      renal, respiratory, gastrointestinal, and hematologic failures, developed as a
      sign of multiple organ failure following liver failure in most patients or
      preceding liver failure in a few patients. None of the six patients with four or
      more organ failures survived. Hepatectomy for hilar cholangiocarcinoma is risky
      owing to impaired hepatic functional reserve in jaundiced patients and the
      technical difficulty associated with hepatobiliary resection. Our goal is to
      reduce mortality to less than 5% while keeping a high resectability rate (above
      80%).

PMID- 11596891
TI  - Surgical complications and treatment during resection for malignancy of the high
      bile duct.
AB  - From January 1968 to January 1997 a series of 50 of 109 patients had undergone
      resection for high bile duct cancer in our institution in Rennes, France. The
      overall operative mortality was 12%, but there were no deaths among those who had
      only tumor resection or those with hepatectomy with vascular reconstruction. The
      early complications were biliary fistula (four cases) and subphrenic abscess
      (three cases), of which two of the biliary fistulas resulted in mortality. There
      were three gastrointestinal hemorrhages; one was due to gastritis related to
      hepatorenal insufficiency and was fatal. Two other deaths were due to respiratory
      failure and ascites associated with hepatic insufficiency. In one patient after
      liver transplantation with cluster resection, a biliary leak and ileocolic
      fistula were the cause of postoperative mortality. Another patient suffered a
      ruptured mycotic aneurysm after pretransplant transtumoral intubation, which
      emphasizes the risk of infection in an immunosuppressed patient. The main late
      complication was cholangitis (8 cases). This complication is most often a symptom
      of recurrence (four cases). Some are due to benign causes (intrahepatic
      lithiasis, intrahepatic foreign body granuloma). Surgical exploration is
      mandatory to exclude benign complications, which can then be treated
      palliatively. Four patients presented with recurrence but without cholangitis. In
      conclusion, the causes of complications after resection of high bile duct cancer
      should be carefully assessed to choose the correct treatment. Late cholangitis is
      a symptom of recurrence, but it should be explored and managed precisely.

PMID- 11596892
TI  - Endoscopic stenting for malignant biliary obstruction.
AB  - Use of endoscopic stents to manage patients with malignant obstructive jaundice
      is a well accepted measure. Interpretation of the results of endoscopic stenting
      must be made with reference to the level of the bile duct obstruction. Results
      were generally unsatisfactory for hilar lesions, especially when the intrahepatic
      ducts were segregated into multiple isolated systems. After deployment, stent
      dysfunction due to clogging by biliary sludge is apparently an inevitable process
      for the conventional plastic stent. Considerable efforts had been made to prolong
      the stent patency by changing its physical configuration, coating the inner
      lumen, and the choice of material but with little success. The development of a
      self-expandable metal stent is a major advance, but the benefits derived from a
      larger stent lumen are compromised by the initial expense and the tumor ingrowth
      through the wires for all models available commercially. Current data failed to
      substantiate the value of routine preoperative biliary decompression, as there is
      no reduction in the morbidity and mortality rates after surgery. Although biased
      patient selection may have resulted in the negative observations made, repeated
      clinical trials should probably focus on patients with distal bile duct tumors
      who are preparing for a major pancreatic resection. As a definitive palliative
      measure, endoscopic stenting is a more cost-effective option than surgery for
      patients with limited life expectancy based on data regarding plastic stents. The
      recommendations are evolving however, as there is progressive refinement of
      laparoscopic surgery techniques and designs of endoscopic stents.

PMID- 11596893
TI  - Complications of biliary tract in liver transplantation.
AB  - Bile duct leaks and stenosis, although greatly reduced in their incidence, still
      play a major role in early and late graft loss. Their pathogenesis is
      multifactorial, being related to graft quality, ischemia time, arterial blood
      flow, and, of course, technical mishaps. The diagnosis and treatment of biliary
      complications is nowadays a joint effort among surgeons, interventional
      radiologists, and gastroenterologists. The correct algorithm in obtaining a fast
      diagnosis and the correct therapeutic approach are necessary to save the graft,
      avoid retransplantation or recipient death. Although this may seem to be a simple
      and basic concept, it assumes tremendous importance in liver transplantation in
      which the differential diagnosis between biliary and arterial complications or
      graft rejection and malfunctioning is often a difficult one.

PMID- 11596894
TI  - Biliary anastomotic complications in 400 living related liver transplantations.
AB  - The purpose of this study was to evaluate the cause and outcome of biliary
      anastomotic complications occurring after living related liver transplantation
      (LRLT). A database of 391 patients undergoing 400 LRLT from June 1990 to August
      1998 was reviewed. The overall incidence of biliary anastomotic complications was
      18.2% (71 patients). There were 45 bile leaks, 35 anastomotic strictures, and the
      bile duct was ligated inadvertently in 3 cases. Univariative analysis revealed
      that the manner of stent usage, intrapulmonary shunting, and gender of recipients
      were significant risk factors for leakage. Anastomotic leaks, cytomegalovirus
      infection, hepatic artery complications, and gender of recipients were
      significant risk factors for stricture. In pediatric patients older than 2 years
      old, ABO blood type compatibility was another risk factor for leakage and
      stricture. Choice of stent usage and earlier transplantation for patients with
      intrapulmonary shunting should reduce the rate of biliary leaks, and prophylaxis
      of leaks for patients with intrapulmonary shunting, and minimizing hepatic artery
      complications should reduce the rate of biliary stricture after LRLT. Avoidance
      of ABO-incompatible donors or innovative immunosuppression in ABO-incompatible
      transplantation should be considered in children.

PMID- 11596895
TI  - Choledochocholedochostomy conversion to hepaticojejunostomy due to biliary
      obstruction in liver transplantation.
AB  - Choledochocholedochostomy with tutor (CC-T) or without (CC) is the technique of
      choice for biliary reconstruction in orthotopic liver transplantation (OLT),
      however, its rate of complications is high and does not decrease significantly
      over the years. Biliary obstruction is the most frequent complication and
      surgical treatment frequently involves conversion to hepaticojejunostomy (H-J).
      Out of 412 patients (448 OLTs) analyzed retrospectively, 74 (18%) presented
      biliary complications and 25 (6%) required conversion to H-J because of biliary
      obstruction, generally due to anastomotic stenosis (17 patients, 68%). Sixteen
      out of the 25 presented after the first 3 months, and in two patients, stenosis
      was secondary to arterial thrombosis. Anastomotic stenosis was more frequent in
      the CC group than in the CC-T group (9.9% versus 2.6%, p < 0.05). Sixteen
      patients (64%) underwent percutaneous dilatations, but the response was only
      transitory. There were no postoperative deaths. At the follow-up, three (12%) of
      the 17 surviving patients presented episodes of cholangitis which required
      percutaneous dilatations (1), revision of the H-J (1), or conversion to
      hepaticojejunoduodenostomy (1). Mean survival of patients with H-J was 70.9%, and
      the actuarial survival rate was 68% at 5 years. This does not differ from the
      actuarial survival in our series of transplanted patients (65%). CC or CC-T (in
      selected cases) is an adequate biliary reconstruction for OLT, in spite of the
      fact that a small number of patients will require conversion to H-J. H-J is an
      excellent technique of rescue in cases of biliary obstruction that are not
      possible to resolve by percutaneous dilatations.

PMID- 11596896
TI  - Complications following repair of extrahepatic bile duct injuries after blunt
      abdominal trauma.
AB  - Extrahepatic bile duct traumatic injuries are extremely rare and their treatment
      is difficult and with several controversies. The aim of this study was to offer
      some more clinical information on their surgical repair and outcome. We present
      seven patients with extrahepatic biliary tract lesions after blunt abdominal
      trauma, (isolated gallbladder lesions were excluded) four males and three females
      from 23 to 51 years of age (mean age 35.1 years). All patients had suffered high
      energy blunt abdominal trauma and presented associated injuries, mostly liver
      trauma and lung contusions. Six gallbladder lesions and six common bile duct
      injures were identified; a right hepatic duct laceration and a left hepatic duct
      transection were also present. Injuries were treated either with primary repair
      or with duct-jejunal anastomoses with Roux-en-Y reconstruction. Principal
      complications were postoperative anastomotic leakage (1 case) and recurrent
      cholangitis (3 cases) with or without stricture. Not-diagnosed injuries caused
      substantial morbidity. We prefer and recommend the use of primary repair in
      partial ruptures with no significant tissue loss and biliary-enteric anastomoses
      in large injuries and complete transections because they offer the best long-term
      drainage with less risk of stricture formation than end-to-end anastomoses. We
      defend the use of long duration (6 to 9 months) transanastomotic stents.

PMID- 11596897
TI  - Laparoscopic surgery and the common bile duct.
AB  - Many biliary tract surgeons have now reached a level of sophistication with
      laparoscopic cholecystectomy that they are now able to deal with the common bile
      duct at the same time. Preoperative endoscopic cholangiography can be reserved
      for cases where choledocholithiasis has a high degree of probability. This has
      served to decrease the number of negative studies. The surgeon has five choices
      regarding stones confirmed by operative cholangiography during laparoscopic
      cholecystectomy: (1) do nothing, hoping the stones will pass spontaneously or
      that a postoperative sphincterotomy with stone extraction will be successful; (2)
      perform a transcystic laparoscopic common bile duct exploration (best for stones
      less than 1 cm and distal to the cystic duct); (3) perform a laparoscopic common
      bile duct exploration by choledochotomy (best for large stones in patients with
      common bile ducts greater than 1 cm. It is also the preferred approach with
      stones proximal to the insertion of the cystic duct.); (4) perform an
      intraoperative sphincterotomy with stone extraction, either retrograde or
      antegrade (this approach has some proponents but has not gained popularity among
      the majority of surgeons); and (5) place a double lumen catheter through the
      cystic duct with a proximal lumen in the common bile duct and the distal lumen in
      the duodenum. This can be used for serial postoperative cholangiography to
      confirm spontaneous stone passage or falsely positive operative cholangiograms.
      It is useful in situations when laparoscopic common bile duct exploration
      equipment or surgeon expertise is not available. If stones persist, a guidewire
      can be introduced through the distal lumen of the catheter for a guidewire
      assisted sphincterotomy. Other CBD interventions that have been reported include
      laparoscopic biliary bypass and resection of choledochal cysts. Malignant lesions
      should not be approached by a laparoscopic method except in unusual
      circumstances.

PMID- 11596898
TI  - Incidence, risk factors, and prevention of biliary tract injuries during
      laparoscopic cholecystectomy in Switzerland.
AB  - Bile duct injury (BDI) during laparoscopic cholecystectomy (LC) which may result
      in patient disability or death are reported to occur more frequently when
      compared to open surgery. The aim of this nationwide prospective study beyond the
      laparoscopic learning curve was to analyze the incidence, risk factors, and
      management of major BDI. During a 3-year period (1995-1997) 130 items of all LC
      data were collected on a central computer system from 84 surgical institutions in
      Switzerland by the Swiss Association of Laparoscopic and Thoracoscopic Surgery
      and evaluated for major BDIs. Simple biliary leakage was excluded from analysis.
      There were 12,111 patients with a mean age of 55 years (3-98 years) enrolled in
      the study. The overall BDI incidence was 0.3%, 0.18% for symptomatic gallstones,
      and 0.36% for acute cholecystitis. In cases of severe chronic cholecystitis with
      shrunken gallbladder, the incidence was as high as 3%. Morbidity and mortality
      rates were significantly increased in BDIs. BDI was recognized intraoperatively
      in 80.6%, in 64% of cases by help of intraoperative cholangiography. Immediate
      surgical repair was performed laparoscopically (suture or T-drainage) in 21%; in
      79%, open repair (34% simple suture, 66% Roux-en-Y reconstruction) was needed.
      The BDI incidence did not decrease during the last 7 years. In 47%, BDIs were
      caused by experienced laparoscopic surgeons, perhaps because they tend to operate
      on more difficult patients. In conclusion, the incidence of major BDIs remains
      constant in Switzerland at a level of 0.3%, which is still higher when compared
      to open surgery. However, most cases are now detected intraoperatively and
      immediately repaired which ensures a good long-term outcome. For preventing such
      injuries, exact anatomical knowledge with its variants and a meticulous surgical
      dissecting technique especially in case of acute inflammation or shrunken
      gallbladder are mandatory.

PMID- 11596899
TI  - Is there a place for laparoscopy in management of postcholecystectomy biliary
      injuries?
AB  - Despite its minimal invasiveness, laparoscopic cholecystectomy (LC) carries
      unquestionably higher morbidity and mortality rates when compared with the open
      counterpart (OC). Among the iatrogenic injuries, biliary tract lesions are the
      most clinically relevant because of their potential for patient's disability and
      long-term sequelae. No universal agreement exists for classifying these lesions,
      but numerous authors have advocated a distinction between bile leaks and bile
      injuries. Even if not entirely correct, bile leaks refer to fistulas from minor
      ducts in continuity with the major ductal system or from accessory ducts (as the
      duct of Luschka). Biliary injuries are major complications consisting of leaks,
      strictures, transection, or ligation of major bile ducts. While bile leaks are
      typically treated by percutaneous and/or endoscopic drainage and stenting,
      biliary injuries often require a combined radiology-assisted and endoscopic
      approach or even conventional surgery. The role of laparoscopy in the management
      algorithm of biliary lesions is still anecdotal. To date, a total of 25 cases of
      laparoscopic drainage of post-cholecystectomy bilomas have been reported in the
      literature, whereas there is no mention of laparoscopic primary repair of biliary
      injuries detected at or after cholecystectomy. The main reasons depend on the
      excellent results achieved by the ancillary techniques; the emergency settings
      that accompany more complex biliary lesions; the technical challenges posed by
      the presence of inflammation, collections, and obscured anatomy; and the
      potential for malpractice litigation. However, a sound laparoscopic technique and
      a strict adherence to basic surgical tenets are crucial in order to avoid the
      incidence of iatrogenic biliary injuries and reduce their still unknown impact on
      long-term patient disability.

PMID- 11596900
TI  - Surgical repair after bile duct and vascular injuries during laparoscopic
      cholecystectomy: when and how?
AB  - Recent collective reviews have outlined when and how surgeons should treat
      patients with bile duct injuries after laparoscopic cholecystectomy (LC).
      However, little is described about other injuries combined with bile duct
      injuries, for example, hepatic arterial injury and secondary biliary cirrhosis.
      Fifteen patients with bile duct injuries following LC were referred and
      surgically treated from 1990 to 1998 in our institution. We report how patients
      with hepatic arterial injury combined with bile duct injuries during LC were
      treated. The present study also reports unusual complicated situations: one
      patient with biliary cirrhosis referred 4 years after LC, another treated with
      internal biliary metallic stent referred 2.5 years after LC, and another with
      isolated right hepatic ductal injury. Short- and long-term surgical outcomes
      after biliary repair were compared between simply referred patients and those
      with complicated history. Patients who were referred several years after LC and
      who were referred after primary hepaticojejunostomy were included with patients
      with complicated history (n = 4, group B), and the other patients were included
      with patients with simple history (n = 11, group A). Simultaneous right hepatic
      arterial occlusion was observed in 3 of these 15 patients, and arterial
      reconstruction was performed in 2 of the 3 patients in addition to biliary
      reconstruction. No postoperative complication occurred in these three patients.
      The patient with isolated injury of the right hepatic duct and the other with
      biliary cirrhosis were successfully treated with hepaticojejunostomy. The other
      patient treated with biliary stent underwent hepaticojejunostomy but a second
      operation was required because of later stenosis. Mean hospital stay was
      significantly longer in group B (30.3 +/- 6.9 days) than in group A (18.5 +/- 2.5
      days, p< 0.05). Rehospitalization was more frequent in group B than in group A (p
      < 0.01). However, long-term outcome was successful in both groups. The present
      results showed that arterial reconstruction should be performed when the distal
      right hepatic artery can be exposed and reconstructed, and suggested that
      patients with bile duct injuries during LC should be immediately referred to
      surgical institutions in which surgeons have adequate experience of bile duct
      repair and hepatic arterial reconstruction.

PMID- 11596901
TI  - Treatment of common bile duct injuries during laparoscopic cholecystectomy:
      endoscopic and surgical management.
AB  - The increase of laparoscopic cholecystectomy has resulted in an increase of bile
      duct injuries. The purpose of this article is to define the types of injury,
      their occurrence and frequency, and their management by endoscopic and surgical
      techniques. Three investigations were included in the present study. 1. A 3-year
      retrospective study among 29 hospitals with 25,007 laparoscopic
      cholecystectomies. 2. An 8-year prospective study at our institution of 6488
      patients. 3. A prospective endoscopic study of 94 patients with injuries and
      strictures of the common bile duct (CBD) after laparoscopic cholecystectomy. A
      special classification for bile duct injuries was developed. Among 25,007
      patients from 29 hospitals, a total of 74 lesions were detected with an incidence
      of 0.29%. At our institution, 20 cases were seen (0.29%) with type I, II, and III
      injuries. The 94 cases managed by endoscopic procedure were submitted to
      endoscopic retrograde cholangiopancreatography (ERCP) and papillotomy, with
      placement of several stents 5 to 10 F during 8 months. The results of this
      procedure have been excellent to good in 76% of the cases up to 3 years of follow
      up. According to our previous and present experience, bile duct injuries after
      laparoscopic procedure are two times higher than after open procedure. The best
      treatment is the prevention of these injuries by careful surgical technique. If
      they occur, the best moment to repair them is during surgery. If they are noticed
      after the operation, endoscopic or surgical procedures can be employed.

PMID- 11596902
TI  - Safety of laparoscopic approach for acute cholecystitis: retrospective study of
      609 cases.
AB  - Laparoscopic cholecystectomy (LC) is now widely accepted as the modality of
      choice for the treatment of symptomatic uncomplicated cholelithiasis. The
      application of the laparoscopic technique in the setting of acute cholecystitis
      (AC) is more controversial. The precise role as well as the potential benefits of
      LC in the treatment of the acutely inflamed gallbladder have not been clearly
      established through large clinical series. The aim of our study was to assess the
      feasibility, safety, benefits, and specific complications of the laparoscopic
      approach in patients with AC. A retrospective chart analysis involving the
      patients admitted to two busy emergency digestive surgical units between October
      1990 and December 1997 was carried out. Six hundred and nine patients meeting our
      criteria for AC were identified and evaluated. Overall complication rate was 15%
      with 12 postoperative bile leakages (1.97%) and 4 biliary tract injuries (BTI)
      (0.66%). The overall mortality rate was 0.66%. Local and overall complication
      rates were significantly correlated with the delay between the onset of acute
      symptoms and the operation but not the rate of general complications nor deaths.
      Our results demonstrate the safety and feasibility of LC in the setting of AC.
      Early cholecystectomy within 4 days is strongly recommended to minimize
      complications and increase the chances of a successful laparoscopic approach.

PMID- 11596903
TI  - Transduodenal sphincterotomy in laparoscopic era.
AB  - Indications for transduodenal sphincterotomy have been reduced in recent years,
      mainly because of the development of endoscopic sphincterotomy and laparoscopic
      procedures. Endoscopic treatment is effective, but it is necessary to carefully
      evaluate its indications because the incidence of early and late complications is
      not negligible. Laparoscopic procedures require advanced and expensive
      technologies and considerable laparoscopic experience. Transduodenal
      sphincterotomy is safe and effective, if correctly performed. Some risk factors
      appear to be related to the incidence of complications that do not significantly
      differ from those following endoscopic sphincterotomy. Transduodenal
      sphincterotomy may be still indicated in selected cases, and for this reason it
      should be considered an essential part of the knowledge of a general surgeon.

PMID- 11596904
TI  - Surgical therapy of iatrogenic lesions of biliary tract.
AB  - Iatrogenic injuries of the biliary tract have increased in incidence over the
      past decade with the introduction of laparoscopic cholecystectomy. Although a
      number of factors have been identified with a higher risk of injury (male gender,
      complicated gallstone disease, aberrant anatomy) and a number of technical steps
      have been emphasized to avoid these injuries, the incidence of bile duct injuries
      has reached a steady-state at least double the rate observed with open
      cholecystectomy. Most patients sustaining a bile duct injury are recognized in
      the weeks following laparoscopic cholecystectomy. Careful preoperative
      preparation should include control of sepsis by draining any bile collections or
      fistulas and complete cholangiography. Long-term results are best achieved in
      specialized hepatobiliary centers performing biliary reconstruction with a Roux
      en-Y hepaticojejunostomy. Success rates over 90% have been reported from several
      centers to date with intermediate follow-up.

PMID- 11596905
TI  - Metabolites of the L-arginine-NO pathway in patients with left-to-right shunt.
AB  - OBJECTIVES: The endogenous production of metabolites of the L-arginine-NO pathway
      has been found to be altered in patients with left-to-right shunt and pulmonary
      hypertension. The objective of this study was to analyze the influence of age and
      of the magnitude of the left-to-right shunt on plasma levels of L-arginine,
      cyclic guanosine monophosphate (cGMP), nitrite and nitrate in children and young
      adults presenting with left-to-right shunt. METHODS: Twenty-nine patients with
      ventricular septal defect (n=18), atrial septal defect (n=6) and atrioventricular
      canal (n=5) were assigned to group I when the ratio of pulmonary to systemic
      blood flow (Qp/Qs) was less than 1.5 (n=10) and to group II when Qp/Qs > or = 1.5
      (n=19). At cardiac catheterization blood samples were taken from the pulmonary
      vein or left ventricle. In 33 controls peripheral venous blood was obtained. cGMP
      levels were determined by radioimmunoassay, L-arginine, nitrite and nitrate by
      high performance liquid chromatography (HPLC). RESULTS: L-arginine plasma levels
      were lower in group II than in controls (51.7 [23.3-82.2] versus 60.5 [32.4-85.9]
      pmol/l; p < 0.05 by KRUSKAL-WALLIS). Age did not influence the L-arginine plasma
      levels (p = 0.30). cGMP levels depended on age (p<0.01) and mean pulmonary artery
      pressure (p <0.01) but not on high pulmonary blood flow (p=0.85; ANOVA). Plasma
      nitrite and nitrate were not different in both groups and when compared with
      controls (nitrite: 26.0 [23.5-31.0] micromol/l; nitrate: 26.8 [24.0-32.0]
      micromol/l). CONCLUSIONS: Age and pulmonary artery pressure exert important
      effects on plasma cGMP. Measurement of nitrite and nitrate in plasma alone may
      not reflect the endogenous NO production. Future studies should evaluate the role
      of plasma levels of L-arginine in patients with high pulmonary blood flow
      undergoing repair of their defect.

PMID- 11596906
TI  - Reduction of preanalytical errors due to in vitro activation of coagulation.
AB  - Statistically significant errors due to activation of coagulation may result from
      the blood sampling procedure. In order to establish the magnitude of errors,
      blood sample aliquots were drawn in triplicate from one venipuncture. A procedure
      is described for discrimination of inappropriate analytical results in 162
      subjects. Estimated percentages of insufficient duplicate results amounted to 36%
      for thrombin-antithrombin complexes, to 5% for prothrombin fragment 1+2, to 2%
      for fibrinogen degradation products and to 4% for fibrin degradation products. It
      is concluded that the overall reliability of results for coagulation analytes can
      be considerably improved by drawing blood samples in triplicate and subsequent
      rejection of samples with inappropriate reproducibility for thrombin
      antithrombin. Routine parameters like prothrombin time or activated partial
      thromboplastin time in normal conditions are not susceptible for the phenomenon
      of coagulation activation.

PMID- 11596907
TI  - Plague and other human infections caused by Yersinia species.
AB  - With an estimated 100 million victims, pandemically and epidemically occurring
      plague has been looked upon as a classical scourge of mankind during the last two
      millenia. Without treatment at least 50% of the affected individuals die from
      infection with Yersinia pestis, a bacterium belonging to the family of
      Enterobacteriaceae. The disease takes a fulminant course. After an incubation
      period of 2-6 days, bubonic plague primarily attacks one group of lymph nodes.
      The onset of pulmonic plague, transmitted by droplet infection, takes place
      within several hours and causes bronchopneumonia. Early recognition facilitates a
      promising antibiotic therapy with tetracycline, streptomycin or chloramphenicol.
      Human beings acquire the bacteria through bites of fleas from domestic rats in
      densely populated cities of countries with low hygienic standards, or
      sporadically in the open country from infected wild rodents. Laboratory procedure
      includes microscopy supplemented by immunofluorescence and cultivation of the
      bacterium from clinical material. Direct serology and PCR result in a fast
      detection of specific antigens or nucleotide sequences. Determination of serum
      antibodies is principally used for epidemiological investigation. Today,
      physicians in the civilized western world lack experience for the recognition of
      plague, and analytical techniques for diagnosis are only available in some
      specialized laboratories. Yersiniosis becomes primarily manifest as
      gastroenteritis caused by Yersinia enterocolitica or as pseudoappendicitis caused
      by Yersinia pseudotuberculosis and requires antibiotics only in severe septic
      cases. Different extraintestinal symptoms may be observed in dependence on the
      patient's HLA type and gender. The ubiquitous germ is mainly transmitted by the
      fecal-oral route via infected domestic or farm animals and contaminated food. The
      relevant virulence factors are encoded on a 70 kB plasmid common to all Yersinia
      species and strains that are human pathogens. The most important tools for
      laboratory diagnosis are culture from suitable body fluids and serological
      detection of specific antibodies. The infection rate among healthy individuals in
      Europe in terms of percentage of elevated IgA or IgG titers has been quoted to be
      3-40% in different investigations but does not significantly correlate to direct
      bacteriological detection.

PMID- 11596908
TI  - Coeliac disease, anaemia and pregnancy.
AB  - We have investigated the prevalence of positive serology for coeliac disease in
      pregnant women, using the IgA anti-endomysium antibody test. Five of 216 pregnant
      women with a haemoglobin less than 11 g/dl were positive, compared to 0/350 with
      haemoglobin > or = 11 g/dl. Four of these five had low plasma ferritin levels,
      indicative of iron deficiency anaemia; the fifth was borderline normal. We found
      no association between positive coeliac disease serology and folate deficiency.
      None of thirty mothers of children born with neural tube defects were IgA anti
      endomysium antibody positive. This study has identified a very high prevalence of
      occult coeliac disease in pregnancy and a strong association with anaemia. We
      advise that in cases with a haemoglobin of less than 11 g/dl in pregnancy,
      coeliac disease should be excluded.

PMID- 11596909
TI  - Simultaneous determination of the new HIV protease inhibitor lopinavir (ABT 378)
      and of indinavir(1), amprenavir, saquinavir, ritonavir (ABT 538)(2) and
      nelfinavir(3) in human plasma by gradient HPLC.
AB  - Protease inhibitors are known by their inhibition of a viral protease that leads
      to production of immature and non-infectious virus particles. The novel protease
      inhibitor KALETRA is a co-formulation of lopinavir and ritonavir. Ritonavir
      reduces the metabolization of lopinavir by the cytochrome P450 3A4 isoenzyme
      which leads to markedly increased plasma levels of lopinavir(4). A new rapid and
      sensitive HPLC method for the simultaneous determination of lopinavir, indinavir,
      amprenavir, saquinavir, ritonavir and nelfinavir in human plasma has been
      developed. An aliquot of 500 microl plasma, spiked with internal standard, was
      extracted with 500 microl 0.1 M ammonium hydroxide solution and 5 ml tert. -butyl
      ether. After drying under a nitrogen stream, the residue was redissolved in an
      eluent consisting of 50 mM phosphate buffer, pH 5.40 and acetonitrile (50:50,
      v/v). Chromatographic separation was accomplished on a C-18 column using a non
      linear gradient elution and ultraviolet detection at 215 nm.

PMID- 11596910
TI  - Evidence-based laboratory medicine.
AB  - Evidence-based medicine (EBM) is a method for solving problems concerning the
      assessment of laboratory testing in patient care. Practising EBM involves the use
      of the available evidence to make health care decisions. The best way to practice
      EBM is the development, validation and implementation of guidelines. Guidelines
      are considered as the process by which healthcare research and experience are
      translated into improved patient care. In laboratory diagnostics EBM can be best
      demonstrated in high-prevalence conditions. Because of the number of patients
      encountered, high-prevalence conditions have a greater impact on patient
      morbidity and health care expenditure. In evidence-based laboratory medicine the
      best evidence comes from systematic reviewing studies of diagnostic tests. The
      reviewing of diagnostic trials and the development of good practice guidelines on
      the basis of these studies must be an important task of the scientific
      associations of clinical chemistry and laboratory medicine.

PMID- 11596911
TI  - Cardiac troponin I: a biomarker for detection and risk stratification of minor
      myocardial damage.
AB  - Myocardial infarction has long been a subject of research in cardiology and
      biochemistry. Within the past few years, a number of new phrases, micro
      infarction, minor cardiac damage and non-ischemic cardiac damage have been
      frequently used and discussed since cardiac troponin I (cTnI) was introduced.
      Using this sensitive and specific biomarker it is now possible to detect minor
      cardiac damage occurring in different clinical settings: spontaneous, trauma,
      thermal injury, septic shock, or during cardiovascular surgery. The advent of
      this marker also opens a subject on the pathophysiologic aspect of non-ischemic
      cardiac damage that has not yet been fully understood and verified. This article
      reviews current knowledge of cTnI and its relationship with unstable angina and
      non-ischemic cardiac damage. The clinical implication of recent research findings
      on cTnI is also discussed.

PMID- 11596912
TI  - Influence of psychosocial resources on the relationship between lifestyle and
      cardiovascular or mental health.
AB  - Among middle-aged women: The factor beta-lipoproteins is significantly influenced
      by cigarette smoking and by the intensity of physical activity at leisure time.
      The factor alpha-lipoproteins is not influenced by these lifestyle factors. The
      leukocyte count is higher among smokers. It is not significantly associated with
      other inflammation markers. The pre-diabetic risk profile is improved by physical
      activity at leisure time and by rigid eating behaviour in stressful situations.
      The physical activity at leisure time and a rigid eating behaviour in stressful
      situations play a positive role for mental health, too. Styles of coping with
      stress, action styles or sense of coherence do not influence the relationships
      between lifestyle factors and cardiovascular risk factors. Psychosocial resources
      intensify the relationships between lifestyle and mental health.

PMID- 11596913
TI  - Prediction and diagnosis of type 1 diabetes using beta-cell autoantibodies.
AB  - The clinical manifestation of type 1 diabetes is the endpoint of a long-lasting
      immune-mediated destruction process of the B-cells. Autoantibodies originating
      from this process can be applied in the diagnosis and clinical discrimination of
      autoimmune diabetes as well as in the prediction of this disease. At clinical
      diagnosis between 80-90% of patients with type 1 diabetes are positive for
      antibodies to B-cell antigens, such as ICA and antibodies to glutamic acid
      decarboxylase or IA2. These antibodies can also be detected in the presymptomatic
      period before onset of the disease, and can thus be used to predict type 1
      diabetes. Using a combination of antibodies, diabetes can be predicted in 70-80%
      of future cases of diabetes, with a positive predictive value between 30-80%,
      depending on the type of antibody tested for and the population studied. Between
      5 and 30% of patients initially diagnosed with type 2 diabetes will show
      progression to insulin dependency and turn out to have type 1 within three years
      of diagnosis. It is clinically relevant to identify these patients early in the
      course of disease, as deterioration of metabolic control results in an increased
      risk for macro- and micro-vascular complications. Autoantibodies to glutamic acid
      decarboxylase or ICA are of high diagnostic sensitivity in these cases and are
      better predictors for future insulin dependency than biochemical or clinical
      parameters. Increasing knowledge on the applicability of antibodies for diabetes
      prediction and diagnosis and the development of commercial assays for antibodies
      to glutamic acid decarboxylase and IA2 antibodies has enabled the implementation
      of B-cell autoantibodies in routine diagnostic settings.

PMID- 11596914
TI  - Prevalence of viral markers among blood donors in Tunisia.

PMID- 11596915
TI  - Riding the ciliate cell cycle--a thirty-five-year prospective.
AB  - Studies of the ciliate cell cycle have moved from early examination of its
      biochemistry with heat-synchronized Tetrahymena through descriptive studies of
      Paramecium using small synchronous cell samples. These studies described what
      happens during the cell cycle and provided some initial insights into control,
      especially the idea that there was a point at which cells became committed to
      division. This early work was followed by an analytical phase in which the same
      small sample techniques, combined with gene mutations, were used to tease apart
      some major features of the regulation of cell growth kinetics, including
      regulation of macronuclear DNA content and regulation of cell size, the control
      of timing of initiation of macronuclear DNA synthesis, and the control of
      commitment to division in Paramecium. The availability of new molecular genetic
      approaches and new means of manipulating cells en masse made it possible to map
      out some of the basic features of the molecular biology of cell cycle regulation
      in ciliates. The challenge before us is to move beyond the 'me-too-ism' of
      validating the presence of basic molecular regulative machinery underlying the
      cell cycle in ciliates to a deeper analysis of the role of specific molecules in
      processes unique to ciliates or to analysis of the role of regulatory molecules
      in the control of cell process that can be uniquely well studied in ciliates.

PMID- 11596916
TI  - The ultrastructure of contractile tubules in the heliozoon Actinophrys sol and
      their possible involvement in rapid axopodial contraction.
AB  - We employed an improved fixation procedure for electron microscopy using
      ruthenium red, and found a bundle of contractile tubules inside the axopodia of
      the heliozoon Actinophrys sol. Upon food uptake, the tubules shorten and
      transform into a mass of small granules when rapid axopodial contraction occurs,
      suggesting that these structures are involved in the process of axopodial
      contraction. The relationship between transformation of the contractile tubules
      and accompanying disassembly of the axonemal microtubules was studied by
      examining the ultrastructure of the contractile tubules after disassembly of the
      microtubules was artificially induced by cold or colchicine treatment.
      Granulation of the contractile tubules was induced by cold but not by colchicine
      treatment. During recovery from cold treatment, granular forms of the contractile
      tubules became re-elongated and their initial tubular appearance was restored.
      These results suggest that the contractile tubules in heliozoon axopodia play a
      role in repetitive cytoplasmic contraction.

PMID- 11596917
TI  - Partial cloning of putative G-proteins modulating mechanotransduction in the
      ciliate stentor.
AB  - Signal transduction systems known to utilize G-proteins in higher eukaryotes
      undoubtedly evolved prior to the development of metazoa. Pharmacological evidence
      indicates that the ciliates Paramecium, Stentor, and Tetrahymena all utilize
      signaling systems similar to those found in mammals. However, there has been
      relatively little direct evidence for the existence of G-proteins in ciliates.
      Since highly conserved heterotrimeric G-proteins form the basis of receptor
      coupled signal transduction systems in a wide variety of metazoa, it is of
      interest to know if these important signaling molecules were early to evolve and
      are present and functionally important in a wide variety of unicellular
      organisms. We have previously shown that mechanotransduction in Stentor is
      modulated by opiates in a manner that may involve pertussis toxin-sensitive G
      proteins. Here we utilize drugs known to interact with G-proteins to further test
      for the involvement of these important signaling molecules in Stentor
      mechanotransduction. We present behavioral and electrophysiological data
      demonstrating that putative G-proteins in Stentor decrease mechanical sensitivity
      by modulating the mechanotransduction process. In addition, we report the partial
      cloning of 4 G-protein alpha-subunits from Stentor. We confirm that these clones
      are of Stentor origin and are transcribed. Furthermore, we employ antisense
      oligodeoxynucleotide-mediated knockout to demonstrate that these ciliate G
      proteins exert a modulatory influence on Stentor behavior, and that a G1/G0-like
      clone mediates the inhibitory action of beta-endorphin on mechanotransduction.

PMID- 11596918
TI  - Directed migration of Ascogregarina taiwanensis (Apicomplexa: Lecudinidae) in its
      natural host Aedes albopictus (Diptera: Culicidae).
AB  - Directed migration of trophozoites from the midgut toward the Malpighian tubules
      is essential for Ascogregarina taiwanensis (Apicomplexa: Lecudinidae) to complete
      its developmental cycle within the natural host Aedes albopictus. We have
      obtained a 275-bp actin cDNA fragment amplified from extracted mRNAs of migrating
      trophozoites, suggesting the involvement of actin in trophozoite motility. Down
      regulation on the migration of the trophozoite was seen in mosquito larvae fed
      with cytochalasin D, ML-7, and BDM, indicating that myosin, in the form of an
      actomyosin system, may also be involved in driving motility of the trophozoite.
      The "protruding apparatus" (PA) formed at the anterior end of trophozoites during
      the migrating stage had significant deposits of actin by immunofluorescent
      microscopy. Moreover, PA formation was enhanced in response to elevated levels of
      20-hydroxyecdysone (20-HE) in cultures of alimentary canals in which the
      trophozite was contained. Thus, 20-HE may also promote expression of actin and
      perhaps myosin simultaneously.

PMID- 11596919
TI  - Four new species of Macropodinium (Ciliophora: Litostomatea) from Australian
      wallabies and pademelons.
AB  - Samples of Macropodinium spp. were collected from 3 new macropodid species: from
      21 of 28 (75%) black-striped wallabies (Macropus dorsalis); 10 of 11 (91%) swamp
      wallabies (Wallabia bicolor); and 22 of 43 (51%) Tasmanian pademelons (Thylogale
      billardierii). The examination of ciliate morphology by silver impregnation and
      scanning electron microscopy led to the redescription of the genus Macropodinium
      and the description of 4 new species: Ma. tricresta sp. nov. and Ma. spinosus sp.
      nov. from M. dorsalis; Ma. maira sp. nov. from T. billardierii; and M. bicolor
      sp. nov. from W. bicolor; each species was strictly host specific. Cellular
      orientation was reinterpreted on the basis of vestibular morphology and it is
      concluded that Macropodinium spp. are laterally rather than dorso-ventrally
      compressed. The striated groove is thus dorso-ventral rather than lateral. Oral
      ciliation consisted of up to three bands: an adoral band composed of oblique
      kineties; a vestibular band of longitudinal kineties; and a preoral band of
      longitudinal kineties. Somatic ciliation occurred in two longitudinal bands: a
      dense band composed of several parallel kineties on the left side of the dorso
      ventral groove; and a sparse band composed of a single kinety on the right
      internal side of the dorso-ventral groove. Few structures were homologous to
      those of other litostome ciliates, and thus the relationship of Macropodinium to
      other litostomes cannot yet be clearly defined.

PMID- 11596920
TI  - Differential antibody recognition of four allelic variants of the merozoite
      surface protein-2 (MSP-2) of Plasmodium falciparum.
AB  - The merozoite surface protein-2 (MSP-2) is a major vaccine candidate for the
      asexual blood stage of Plasmodium falciparum. MSP-2 is essentially dimorphic, and
      allelic families are named after the representative isolates FC27 and IC1. The
      polymorphic central region contains immunodominant repeats, which vary in number,
      length, and sequence within and between allelic families. We have examined the
      antibody recognition of repeat regions from both MSP-2 allelic families expressed
      as recombinant fusion peptides. The results are summarized as follows. (1)
      Immunization of mice with the fusion peptides elicited IgG antibodies that cross
      reacted with the native MSP-2 molecule in an allelic family-specific manner. (2)
      These mouse antibodies recognized the recombinant proteins in both a variant
      specific and a family-specific manner, as shown in inhibition immunoassays.
      Antibodies raised against the peptide FC27 seemed to be essentially variant
      specific, since the soluble form of the S20 antigen (a member of FC27 family) had
      relatively little inhibitory effect on them. (3) The overall pattern of human IgG
      antibody responses to MSP-2 in Karitiana Indians, a population continuously
      exposed to hypoendemic malaria in the Brazilian Amazon Region, differs from that
      described in hyperendemic areas in Africa and Papua New Guinea in two important
      features: there was no clear age-dependent increase in the prevalence and mean
      concentration of specific IgG antibodies, and there was no skewing towards the
      IgG3 subclass in antibody responses. (4) The relatively poor correlation between
      concentrations of IgG antibodies that are specific for members of the same
      allelic family suggests that recognition of MSP-2 peptides by naturally acquired
      antibodies was largely variant-specific in this population. The potential role of
      naturally acquired variant-specific antibodies in immune evasion, by selecting
      mutant parasites carrying insertions or deletions of repeat sequences, is briefly
      discussed.

PMID- 11596921
TI  - Quantitation of Cryptosporidium parvum infection in cell culture using a
      colorimetric in situ hybridization assay.
AB  - A quantitative colorimetric in situ hybridization assay was developed for
      detecting Cryptosporidium parvum infection in cell cultures using a digoxigenin
      labeled probe targeting 18S rRNA. Intra-cellular developmental stages of C.
      parvum such as trophozoites and meronts were clearly discerned by light
      microscopy as localized areas of dark purple/black precipitate against a
      colorless background. Infections developed focally and the term infectious focus
      was applied to each cluster of developmental stages. There were no significant
      differences in the number of infectious foci following 24 h or 48 h incubation.
      However, 24 h and 48 h dose response curves were significantly different when
      infectivity was measured as the number of developmental stages per monolayer,
      with an average of 5.3-fold more stages following 48 h incubation. When
      infectivity was expressed as the number of infectious foci per inoculum oocyst
      converted to a percentage, it was demonstrated that the rate of infection
      decreased with increasing oocyst age. Oocysts of the Iowa isolate that were 7-10
      days old demonstrated 7.8+/-2.4% infectivity (mean +/- standard deviation)
      compared to 4.2+/-0.8% for 21-28 day-old oocysts and 1.4+/-1.3% for 42-70 day-old
      oocysts. The assay also detected infection with other genotype 2 oocysts and a
      genoptye 1 isolate. This assay provides a direct quantitative approach for
      measuring C. parvum infectivity in cell culture.

PMID- 11596922
TI  - Programmed translational frameshifting is likely required for expressions of
      genes encoding putative nuclear protein kinases of the ciliate Euplotes
      octocarinatus.
AB  - Three macronuclear genes encoding putative nuclear protein kinases of the ciliate
      Euplotes octocarinatus syngen 1 were isolated and sequenced. All three deduced
      gene products share significant properties with a group of recently identified
      nuclear serine/threonine protein kinases named Ndr. The three predicted proteins
      contain the twelve conserved catalytic subdomains of protein kinases and 22 near
      universally-conserved amino acids residues that are characteristic of
      serine/threonine protein kinases. In addition, there is an approximately 30 amino
      acid-peptide insertion between subdomains VII and VIII that contains a potential
      nuclear localization signal. Sequence analysis suggests that expression of the
      Eondr2 gene requires a + 1 programmed translational frameshift for its
      translation. Comparison of the deduced EoNdr2 with other known Ndr protein
      kinases implies that a + 1 ribosomal frameshift occurs at the motif AAATAA.

PMID- 11596923
TI  - Phylogenetic relationships of the subclass peritrichia (Oligohymenophorea,
      Ciliophora) with emphasis on the genus Epistylis, inferred from small subunit
      rRNA gene sequences.
AB  - The peritrichs have been recognized as a higher taxon of ciliates since 1968.
      However, the phylogenetic relationships among them are still unsettled, and their
      placement within the class Oligohymenophorea has only been supported by the
      analysis of the small subunit rRNA gene sequence of Opisthonecta henneguyi. DNA
      was isolated directly from field-sampled species for PCR, and was used to resolve
      relationships within the genus Epistylis and to confirm the stability of the
      placement of peritrichs. Small subunit rRNA gene sequences of Epistylis
      plicatilis, Epistylis urceolata, Epistylis chrysemydis, Epistylis hentscheli,
      Epistylis wenrichi, and Vorticella campanula were sequenced and analyzed using
      both distance-matrix and maximum-parsimony methods. In phylogenetic trees, the
      monophyly of both the genus Episrylis and the subclass Peritrichia was strongly
      supported, while V. campanula clustered with Vorticella microstoma. The topology
      in which E. plicatilis and E. hentscheli formed a strongly supported sister clade
      to E. urceolata, E. chrysemydis, and E. wenrichi was consistent with variations
      in the thickness of the peristomial lip. We concluded that the peristomial area,
      especially the peristomial lip, might be the important phylogenetic character
      within the genus Epistylis.

PMID- 11596924
TI  - The sterol composition of Trypanosoma cruzi changes after growth in different
      culture media and results in different sensitivity to digitonin-permeabilization.
AB  - Respiration, oxidative phosphorylation. and the corresponding changes in membrane
      potential (deltapsi) of Trypanosoma cruzi epimastigotes grown either in liver
      infusion-tryptose (LIT) or brain heart infusion (BHI) culture medium were assayed
      in situ using digitonin to render their plasma membrane permeable to succinate,
      ADP, safranine O, and other small molecules. When the cells were permeabilized
      with 64 microM digitonin, a concentration previously used with epimastigotes, the
      ability of the cells grown in LIT medium to sustain oxidative phosphorylation was
      demonstrated by the detection of an oligomycin-sensitive decrease in
      mitochondrial membrane potential induced by ADP. In contrast, the cells grown in
      BHI medium were not able to sustain a stable membrane potential and did not
      respond to ADP addition. Analyses of oxygen consumption by these permeabilized
      cells indicated that the rate of basal respiration, which was similar in both
      cell types, was significantly decreased by 64 microM digitonin. Addition of ADP
      to the permeabilized cells grown in LIT medium promoted an oligomycin-sensitive
      transition from resting to phosphorylating respiration in contrast to the cells
      grown in BHI medium, whose respiration decreased steadily and did not respond
      either to ADP or CCCP. Titration of the cells grown in BHI medium with different
      digitonin concentrations indicated that their mitochondria have higher
      sensitivity to digitonin than those grown in LIT medium. Analysis of the sterol
      composition of epimastigotes grown in the two different media showed a higher
      percentage of cholesterol in total and mitochondrial extracts of epimastigotes
      grown in BHI medium as compared to those grown in LIT medium, suggesting the
      involvement of this sterol in their increased sensitivity to digitonin
      permeabilization.

PMID- 11596925
TI  - Sarcocystis lindsayi n. sp. (Protozoa: Sarcocystidae) from the South American
      opossum, Didelphis albiventris from Brazil.
AB  - A new species, Sarcocystis lindsayi n. sp., is proposed for a parasite resembling
      Sarcocystis falcatula. It was obtained from the lungs and muscles of budgerigars
      (Melopsittacus undulatus) fed sporocysts from a naturally-infected South American
      opossum, Didelphis albiventris, from Jaboticabal, Brazil. Sarcocysts of S.
      lindsayi n. sp. in budgerigars are microscopic, up to 600 microm long and up to
      50 microm wide. The cyst wall is up to 2 microm thick. Ultrastructurally, the
      sarcocyst wall consists of numerous slender villar protrusions (up to 2.0 microm
      long and up to 0.3 microm wide), each with a stylet at its tip. Schizonts in cell
      culture divide by endopolygeny leaving a residual body. Sporocysts are
      approximately 12 x 7 microm. The parasite is genetically distinct from other
      organisms that also cycle between opossums and avian species and resemble S.
      falcatula. Diagnostic genetic variation has been observed in the nuclear large
      subunit ribosomal RNA gene, the internal transcribed spacer (ITS-1), and each of
      two other genetic loci. Although the structure of the sarcocyst wall may not
      provide sufficient grounds for differential diagnosis, several other attributes
      including schizont morphology and genetic variation at each of these genetic loci
      permit identification of S. lindsayi n. sp.. Natural intermediate hosts for S.
      lindsayi n. sp. are not known, and fuller characterization of these and other
      Sarcocystis species would benefit from experimental avian hosts that are more
      permissive to the maturation of sarcocysts.

PMID- 11596926
TI  - Phylogenetic position of Sorogena stoianovitchae and relationships within the
      class Colpodea (Ciliophora) based on SSU rDNA sequences.
AB  - The ciliate Sorogena stoianovitchae, which can form a multicellular fruiting
      body, has been classified based upon its ultrastructure and morphology: the oral
      and somatic infraciliature of S. stoianovitchae most closely resemble those of
      members of the order Cyrtolophosidida in the class Colpodea. We characterized the
      small subunit ribosomal DNA (SSU rDNA) gene sequence from S. stoianovitchae and
      compared this sequence with those from representatives of all ciliate classes.
      These analyses placed S. stoianovitchae as either sister to members of the class
      Nassophorea or Colpodea. In an in-group analysis, including all SSU rDNA
      sequences from members of the classes Nassophorea and Colpodea and
      representatives of appropriate outgroups, S. stoianovitchae was always sister to
      Platyophrya vorax (class Colpodea, order Cyrtolophosidida). However, our analyses
      failed to support the monophyly of the class Colpodea. Instead, our data suggest
      that there are essentially three unresolved clades: (1) the class Nassophorea;
      (2) Bresslaua vorax, Colpoda inflata, Pseudoplatyophrya nana, and Bursaria
      truncatella (class Colpodea); and (3) P. vorax and S. stoianovitchae (class
      Colpodea).

PMID- 11596927
TI  - Regio- and diastereoselective cyclization reactions of free and masked 1,3
      dicarbonyl dianions with 1,2-dielectrophiles.
AB  - Despite their simplicity and synthetic usefulness, cyclisation reactions of 1,3
      dicarbonyl dianions with 1,2-dielectrophiles are problematic, since both dianions
      and 1,2-dielectrophiles are highly reactive compounds (low reactivity matching).
      In addition, 1,2-dielectrophiles are often rather labile, and reactions with
      nucleophiles can result in polymerisation, decomposition, formation of open
      chained products, elimination or SET-reactions. These intrinsic limitations can
      be overcome by a proper reactivity tuning and by the use of electroneutral
      dianion equivalents (masked dianions) in Lewis acid catalysed reactions. The
      cyclisations reported herein allow for an efficient, regio- and stereoselective
      one-pot synthesis of biologically relevant ring systems.

PMID- 11596928
TI  - Step-by-step uncoordination of the pyrazolyl rings of hydrotris(pyrazolyl)borate
      ligands in comlexes of Rh and RhIII.
AB  - Compounds of rhodium(I) and rhodium(III) that contain ancillary
      hydrotris(pyrazolyl)borate ligands (Tp') react with monodentate and bidentate
      tertiary phosphanes in a step-wise manner, with incorporation of P-donor atoms
      and concomitant replacement of the Tp' pyrazolyl rings. Accordingly, [Rh(kappa3
      TpMe2)(C2H4)(PMe3)] (1b), converts initially into [Rh(kappa2-TpMe2)-(PMe3)2] (3),
      and then into [Rh(kappa1-TpMe2)-(PMe3)3] (2) upon interaction with PMe3 at room
      temperature, in a process which can be readily reversed under appropriate
      experimental conditions. Full disengagement of the Tp' ligand is feasible to give
      Tp' salts of rhodium(I) complex cations, for example, [Rh(CO)(dppp)2]-[TpMe2,4
      Cl] (5; dppp = Ph2P(CH2)3PPh2), or [Rh(dppp)2][TpMe2,4-Cl] (6). Bis(hydride)
      derivatives of rhodium(III) exhibit similar substitution chemistry, for instance,
      the neutral complex [Rh(Tp)-(H)2(PMe3)] reacts at 20 degrees C with an excess of
      PMe3 to give [Rh(H)2-(PMe3)4][Tp] (9b). Single-crystal X-ray studies of 9b,
      conducted at 143 K, demonstrate the absence of bonding interactions between the
      [Rh(H)2(PMe3)4]+ and Tp ions, the closest Rh...N contact being at 4.627 A.

PMID- 11596929
TI  - Site distribution in resin beads as determined by confocal Raman spectroscopy.
AB  - Scanning confocal Raman spectroscopy was used to study the distribution of
      reactive sites within a resin bead used for solid-phase synthesis. The
      distribution of NH2 groups in aminomethylated polystyrene resin (APS) was
      determined by doping with varying amounts of 4-cyanobenzoic acid. The extent of
      loading was determined by both elemental analysis and ninhydrin assays. The
      spatial distribution of the coupled 4-cyanobenzamide within the bead was
      determined to an in-plane resolution of 1 microm and depth resolution of about 4
      microm, using the strong Raman CN stretching vibrational transition at 2230 cm(
      1). Dry and swollen beads were studied and the distribution was found to be
      essentially uniform throughout the bead in all cases.

PMID- 11596930
TI  - Spatially resolved single bead analysis: homogeneity, diffusion, and adsorption
      in cross-linked polystyrene.
AB  - Spatially resolved single bead analysis in the micrometer range was employed as a
      tool for evaluating homogeneity, diffusion, and adsorption in solid-phase
      supported reactions. Fluorescence microscopy (confocal and non-confocal) as well
      as IR microscopy were used to detect both the distribution of products and the
      formation of product gradients in representative reactions. For the first time,
      the optical slices of whole beads obtained by confocal fluorescence microscopy
      were compared with the fluorescence images of microtome-sliced beads. The
      experiments revealed that only physical slices of polystyrene beads deliver
      realistic representations of the distribution of fluorophores, and confirmed-in
      contrast to a recent report-the homogeneity of functional site distribution in
      polystyrene beads. Moreover, the pattern of product formation obtained from an
      acylation reaction as well as from an alkylation reaction were employed as probes
      to study the impact of bead size, diffusion, and adsorption on the reaction
      progress. A simulation of the diffusion process was conducted and compared with
      the experimental results. Diffusional control was found neither in the case of
      the alkylation nor in the case of the acylation reaction under investigation. As
      a consequence, the reaction progress was not a function of the bead sizes as
      proposed in the literature. Interestingly, in the case of rhodamine acylation
      with substoichiometric amounts an adsorption-controlled reaction was found. This
      result highlights the significance of adsorptive effects in solid-phase supported
      chemistry.

PMID- 11596931
TI  - Sulfoxides as stereochemical controllers in intermolecular Heck reactions.
AB  - The study of a variety of substituted sulfoxides as chiral auxiliaries in
      intermolecular Heck reactions of sulfinyldihydrofurans and sulfinylcyclopentenes
      with different iodoarenes is reported. In the presence of [Pd(OAc)2]/Ag2CO3 and a
      bidentate phosphine ligand, synthetically useful yields and asymmetric inductions
      were obtained. By far the best diastereoselectivities were obtained by the use of
      the palladium-coordinating O-(N,N-dimethylamino)phenylsulfinyl group. By final
      removal of the chiral auxiliary, these sulfoxide-stereocontrolled asymmetric Heck
      processes were applied to the enantioselective synthesis of 1-aryl-substituted
      and 1,3-diaryl-substituted dihydrofurans and cyclopentenes.

PMID- 11596932
TI  - Interplay of cubic building blocks in (et6-arene)ruthenium-containing tungsten
      and molybdenum oxides.
AB  - A series of molybdenum and tungsten organometallic oxides containing
      [Ru(arene)]2+ units (arene =p-cymene, C6Me6) was obtained by condensation of
      [[Ru(arene)Cl2]2] with oxomolybdates and oxotungstates in aqueous or nonaqueous
      solvents. The crystal structures of [[Ru(eta6-C6Me6]]4W4O16], [[Ru(eta6-p
      MeC6H4iPr]]4W2O10], [[[Ru-(eta6-p-MeC6H4iPr)]2(mu-OH)3]2][[Ru(eta6-p
      MeC6H4iPr)]2W8O28(OH)2[Ru(eta6-p-MeC6H4iPr)(H2O)]2], and [[Ru(eta6
      C6Me6)]2M5O18[Ru(eta6-C6Me6)(H2O)]] (M = Mo, W) have been determined. While the
      windmill-type clusters [[Ru(eta6-arene)]4(MO3)4(mu3-O)4] (M = Mo, W; arene =p
      MeC6H4iPr, C6Me6), the face-sharing double cubane-type cluster [[Ru(eta6-p
      MeC6H4iPr)]4(WO2)2(mu3-O)4(mu4-O)2], and the dimeric cluster [[Ru(eta6-p
      MeC6H4iPr)(WO3)3(mu3-O)3(mu3-OH)Ru(eta6-pMeC6H4iPr)(H2O)]2(mu-WO2)2]2- are based
      on cubane-like units, [(Ru(eta6-C6Me6)]2M5O18[Ru(eta6-C6Me6)(H2O)]] (M = Mo, W)
      are more properly described as lacunary Lindqvist-type polyoxoanions supporting
      three ruthenium centers. Precubane clusters [[Ru(eta6-arene)](MO3)2(mu-O)3(mu3
      O)]6- are possible intermediates in the formation of these clusters. The cluster
      structures are retained in solution, except for [[Ru(eta6-p-MeC6H4iPr)]4Mo4O16],
      which isomerizes to the triple-cubane form.

PMID- 11596933
TI  - Convergent strategies for the attachment of fluorescing reporter groups to
      peptide nucleic acids in solution and on solid phase.
AB  - The site-selective conjugation of peptide nucleic acids (PNA) with fluorescent
      reporter groups is essential for the construction of hybridisation probes that
      can report the presence of a particular DNA sequence. This paper describes
      convergent methods for the solution- and solid-phase synthesis of multiply
      labelled PNA oligomers. The solid-phase synthesis of protected PNA enabled the
      selective attachment of fluorescent labels at the C-terminal end (3' in DNA)
      which demonstrated that further manipulations on protected PNA fragments are
      feasible. For the conjugation to internal sites, a method is introduced that
      allows for the on-resin assembly of modified monomers thereby omitting the need
      to synthesise an entire monomer in solution. Furthermore, it is shown that the
      application of a highly orthogonal protecting group strategy in combination with
      chemoselective conjugation reactions provides access to a rapid and automatable
      solid-phase synthesis of dual labelled PNA probes. Real-time measurements of
      nucleic acid hybridisation were possible by taking advantage of the fluorescence
      resonance energy transfer (FRET) between suitably appended fluorophoric groups.
      Analogously to DNA-based molecular beacons, the dual labelled PNA probes were
      only weakly fluorescing in the single-stranded state. Hybridisation to a
      complementary oligonucleotide, however, induced a structural reorganisation and
      conferred a vivid fluorescence enhancement.

PMID- 11596934
TI  - Pressure- and temperature-induced valence tautomeric interconversion in a o
      dioxolene adduct of a cobalt-tetraazamacrocycle complex.
AB  - An electronic switch at the molecular level has been realized by using a class of
      ionic compounds of the formula [Co(L)(diox)]Y (L = tetraazamacrocyclic ligand, Y
      = mononegative anion). Such compounds undergo temperature- and pressure-induced
      intramolecular one-electron transfer equilibria. The transition temperature of
      interconversion varies with the nature of the counterions Y (Y = PF6, BPh4, I).
      Surprisingly the effect of the anion on the transition temperature is not only
      governed by its volume but also by its coulombic interaction.

PMID- 11596935
TI  - Olefin metatheses in metal coordination spheres: versatile new strategies for the
      construction of novel monohapto or polyhapto cyclic, macrocyclic,
      polymacrocyclic, and bridging ligands.
AB  - The broad applicability of the title reaction is established through studies of
      neutral and charged, coordinatively saturated and unsaturated, octahedral and
      square planar rhenium, platinum, rhodium, and tungsten complexes with
      cyclopentadienyl, phosphine, and thioether ligands which contain terminal
      olefins. Grubbs' catalyst, [Ru(=CHPh)(PCy3)2(Cl)2], is used at 2-9 mol% levels
      (0.0095-0.00042 M, CH2-Cl2). Key data are as follows: [(eta5
      C5H4(CH2)6CH=CH2)Re(NO)(PPh3)-(CH3)], intermolecular metathesis (95 %); [(eta5
      C5H5)Re(NO)(PPh3)(E(CH2CH=CH2)2)]+ TfO (E=S, PMe, PPh), formation of five
      membered heterocycles (96-64%; crystal structure E = PMe); [(eta5
      C5Me5)Re(NO)(PPh((CH2)6CH=CH2)2)(L)]n+ nBF4-(L/n = CO/1, Cl/0), intramolecular
      macrocyclization (94-89%; crystal structure L= Cl); fac
      [(CO)3Re(Br)(PPh2(CH2)6CH=CH2)2] and cis-[(Cl)2Pt(PPh2(CH2)6CH=CH2)2],
      intramolecular macrocyclizations (80-71%; crystal structures of each and a
      hydrogenation product); cis-[(Cl)2Pt(S(R)(CH2)6CH= CH2)2], intra-/intermolecular
      macrocyclization (R=Et, 55%/24%; tBu, 72%/ <4%); trans
      [(Cl)(L)M(PPh2(CH2)6CH=CH2)2] (M/L = Rh/CO, Pt/C6F5) intramolecular
      macrocyclization (90-83%; crystal structure of hydrogenation product, M=Pt); fac
      [W(CO)3(PPh((CH2)6CH=CH2)2)3], intramolecular trimacrocyclization (83 %) to a
      complex mixture of triphosphine, diphosphine/ monophosphine, and
      tris(monophosphine) complexes, from which two isomers of the first type are
      crystallized. The macrocycle conformations, and basis for the high yields, are
      analyzed.

PMID- 11596936
TI  - Thermal rearrangements of 2-vinylcyclopropylidene to cyclopentadiene and
      vinylallene: a theoretical investigation.
AB  - In an attempt to clarify the favored rearrangement reaction of
      vinylcyclopropylidenes, the prototype thermal rearrangements of singlet 2
      vinylcyclopropylidene (1) leading to 1,3cyclopentadiene (2) and 1,2,4-pentatriene
      (vinylallene) (3) were investigated by means of ab initio quantum-mechanical
      electronic-structure calculations. The B3LYP functional with the 6-31G(d) basis
      set was employed for geometry optimization of the equilibrium and transition
      state structures relevant to the two reaction pathways and for computing their
      harmonic vibrational frequencies. Final energies were evaluated by single-point
      calculations at the CCSD(T) level of theory with the 6-311 + G(3df,2p) basis set.
      The rearrangement of s-cis 1 to 2 is found to occur by a three-step pathway. The
      first step involves the formation of a nonclassical carbene (5), which is an
      internal pi complex between the pi molecular orbital of the double bond and the
      empty p atomic orbital of the carbene carbon. In the second step, the nonplanar
      five-membered ring geometry of 5 flattens to reach the planar structure of 3
      cyclopentenylidene (4). The last step is the 1,2-migration of a alpha-hydrogen
      atom to the carbene center in 4. The rate-determining step for the rearrangement
      of s-cis 1 to 2 is the formation of 5, with a predicted global deltaG++(220 K) of
      only 0.6 kcalmol(-1). The rearrangement of s-trans 1 to 2 requires an initial
      conversion of s-trans 1 to the s-cis conformer, with a predicted deltaG++(220 K)
      of 1.8 kcalmol(-1). The transition structure for the ring-opening of s-trans 1
      into s-trans 3 (deltaG++(220 K)=4.7 kcalmol(-1)) is more energetic than that for
      the ring-opening of s-cis 1 into s-cis 3 (deltaG++(220 K)=2.5 kcalmol(-2)) due to
      larger repulsive nonbonded H...H interactions in the former transition structure.
      On the basis of these results, it is suggested that if the reaction of 1,1
      dibromo-2-vinylcyclopropane with methyllithium at -78 degrees C leads to the
      initial formation of carbene 1, then the reaction should yield 2 as the main
      product together with small amounts of 3. This theoretical prediction nicely
      agrees with experimental findings.

PMID- 11596937
TI  - Synthesis and chromatography of [CpRu]+-complexed bastadin precursors.
AB  - The eastern and western diaryl ether portions of the macrocyclic bastadins,
      natural products from the marine sponge Ianthella sp., have been assembled as
      [CpRu]+ complexes. In an HPLC study, aminopropyl-functionalised silica was found
      as a very suitable stationary phase for the chromatographic separation of the
      different cationic ruthenium sandwich complexes. It is now possible for the first
      time to effectively monitor and purify [CpRu]+ complexes and to carry them
      through several synthetic steps.

PMID- 11596938
TI  - Dinuclear titanium(IV) complexes from amino acid bridged dicatechol ligands:
      formation, structure, and conformational analysis.
AB  - Amino acid bridged dicatechol ligands 3a-e-H4 form dinuclear double-stranded
      coordination compounds [(3a-e)2Ti2(OCH3)2]2- with titanium(IV) ions. Due to the
      directionality of the ligands, the chirality of the strand, and the chiral
      complex units, up to seven isomers, I-VII, can be obtained for the double
      stranded complexes of ligands 3a-e-H4. The composition of the mixture of isomeric
      compounds in solution is strongly dependent on the conditions of complex
      formation. Under thermodynamic control, only a few isomers are obtained, one of
      which is the major component of the mixture. X-ray structure analyses were
      performed for K2[(3b)2Ti2(OH)2] and K2[(3d)2Ti2(OH)2] (type I), and for the meso
      complex Na2[(3e)(3e')Ti2(OCH3)2]. A conformational analysis that uses
      Ramachandrans method revealed that the conformation of the amino acids in the
      ligand strands can be compared with those found for amino acids in helical
      peptide structures. The most favored isomer of [(3)2Ti2(OCH3)2]2- appears to be
      of type I, with the catecholamide unit located at the N terminus of the ligand
      strand that binds to a lambda-configurated titanium(IV) complex unit and the
      dihydroxybenzyl group at the C terminus that coordinates to a delta-configurated
      titanium(IV) complex unit. The lambda configuration at the N terminus induces the
      conformation of a right-handed helix in the amino acid residue, while the delta
      configuration induces the less favored left-handed helix.

PMID- 11596939
TI  - Highly efficient synthesis of peptide-oligonucleotide conjugates: chemoselective
      oxime and thiazolidine formation.
AB  - A convergent strategy for the synthesis of peptide-oligonucleotide conjugates
      (POC) is presented. Chemoselective ligation of peptide to oligonucleotide was
      accomplished by oxime and thiazolidine formation. Oxime conjugation was performed
      by treating an oxyamine-containing peptide with an aldehyde-containing
      oligonucleotide or vice versa. Ligation by thiazolidine formation was achieved by
      coupling a peptide, acylated with a cysteine residue, to an oligonucleotide that
      was derivatised by an aldehyde function. For both approaches, the conjugates were
      obtained in good yield without the need for a protection strategy and under mild
      aqueous conditions. Moreover, the oxime ligation proved useful for directly
      conjugating duplex oligonucleotides. Combined with molecular biology tools, this
      methodology opens up new prospects for post-functionalisation of high-molecular
      weight DNA structures.

PMID- 11596940
TI  - Cahn-Ingold-Prelog descriptors of absolute configuration for carbon cages.
AB  - A simplified procedure is described for assigning Cahn-Ingold-Prelog descriptors
      to stereocentres in spheroalkanes (the CnHn molecules, with n even, based on
      trivalent, polyhedral carbon frameworks, a class which subsumes the fulleranes).
      By extension, similar descriptors can be found for the atoms of fullerenes and
      related carbon-only molecules. Assignment maps are given for chiral fullerenes
      C28 C76, C78, C84 and C140, and for a number of spheroalkanes. Cases of breakdown
      of the simple procedure for triangle-rich spheroalkane molecular graphs are
      discussed.

PMID- 11596941
TI  - Imprinting of chiral molecular recognition sites in thin TiO2 films associated
      with field-effect transistors: novel functionalized devices for chiroselective
      and chirospecific analyses.
AB  - (R)- or (S)-2-Methylferrocene carboxylic acids, (R)-1 or (S)-1, (R)- or (S)-2
      phenylbutanoic acid, (R)-2 or (S)-2, and (R)- or (S)-2-propanoic acid, (R)-3 or
      (S)-3, can be imprinted in thin TiO2 films on the gate surface of ion-sensitive
      field-effect transistor (ISFET) devices. The imprinting is performed by
      hydrolyzing the respective carboxylate TiIV butoxide complex on the gate surface,
      followed by washing off the acid from the resulting TiO2 film. The imprinted
      sites reveal chiroselectivity only towards the sensing of the imprinted
      enantiomer. The chiral recognition sites reveal not only chiroselectivity but
      also chirospecificity and, for example, the (R)-2-imprinted film is active in the
      sensing of (R)-2, but insensitive towards the sensing of (R)2-phenylpropanoic
      acid, (R)-3, which exhibits a similar chirality. Similarly, the (R)-3-imprinted
      film is inactive in the analysis of (R)-2. The chiroselectivity and
      chirospecificity of the resulting imprinted films are attributed to the need to
      align and fit the respective substrates in precise molecular contours generated
      in the cross-linked TiO2 films upon the imprinting process.

PMID- 11596942
TI  - Photoluminescent metal-sulfur clusters derived from tetrathiometalates: metal-to
      metal charge-transfer excited states of d0-d10 heterobimetallic sulfido clusters
      with bulky phosphine ligands.
AB  - Reactions of MS4(2-) (M = Mo, W) with M'(PCy3)X (M'=Ag/Au, X= ClO4/Cl) and
      [Cu2(dcpm)2(MeCN)2](ClO4)2 (dcpm = bis(dicyclohexylphosphino)methane) afforded
      heterometallic sulfido clusters [M'2(PCy3)2(MS4)] (M=Mo, M'=Au: 2; M=W, M'=Ag: 3,
      Au: 4) and [Cu4(dcpm)4(MS4)](ClO4)2 (M=Mo: 5 x (ClO4)2, W: 6 x (ClO4)2), all of
      which, except 4, have been characterized by X-ray structure determination.
      Clusters 5 x(ClO4)2 and 6 x (ClO4)2 feature unusual 16-membered [Cu4P5C4]
      metallamacrocycles formed on the respective tetrathiometalate anion templates and
      have unusually long Cu-S bonds and Cu...M distances for metal sulfur clusters
      that contain a saddle-shaped [Cu4MS4] core. Low-energy absorption bands are
      observed in their electronic spectra at approximately 562 and 467 nm,
      respectively, assignable to MMCT transitions; quasireversible reduction waves are
      observed with E(1/2) = -1.43 (52+) and -1.78 V (62+) versus FeCp2(0/+); and they
      are emissive either in the solid state or in solution. The emission of 6(2+) can
      be quenched by both electron acceptors, such as methylviologen, or electron
      donors, such as aromatic amines, with the excited state reduction potential
      E(62+*/6+) estimated to be approximately 1.13V versus a normal hydrogen
      electrode.

PMID- 11596943
TI  - A meso-helical coordination polymer from achiral dinuclear [Cu2(H3CCN)2(micro
      pydz)3][PF6]2 and 1,3-bis(diphenylphosphanyl)propane-synthesis and crystal
      structure of 1 to infinity Cu(mu-pydz)2][PF6 (pydz=pyridazine).
AB  - Reaction of achiral [Cu2(H3CCN)2(mu-pydz)3][PF6]2 (1) (pydz = pyridazine) with
      bidendate 1,3-bis(diphenylphosphanyl)propane (2) in acetonitrile at room
      temperature in a 1:1 ratio yielded the mononuclear copper(I) complex
      [Cu[CH2(CH2PPh2)2]2][PF6] (3) together with new one-dimensional coordination
      polymer 1 to infinity[[Cu(mu-pydz)2][PF6]] (4). Air-sensitive single crystals of
      4, suitable for X-ray structure determination, were grown from a mixture of
      dichloromethane/ hexane [crystal system: monoclinic; space group: C2/c: a =
      21.910(3), b = 12.130(2), c = 25.704(3) A,beta = 110.08(10) degrees, V =
      6416.65(16) A3]. The one-dimensional coordination polymer 1 to infinity[[Cu(mu
      pydz)2][PF6]] (4) exhibits as outstanding feature the rare structure of a meso
      helix.

PMID- 11596944
TI  - Kinetics of dissociative electron transfer to ascaridole and dihydroascaridole
      model bicyclic endoperoxides of biological relevance.
AB  - The homogeneous and heterogeneous electron transfer (ET) reduction of ascaridole
      (ASC) and dihydroascaridole (DASC), two bicyclic endoperoxides, chosen as
      convenient models of the bridged bicyclic endoperoxides found in biologically
      relevant systems, were studied in aprotic media by using electrochemical methods.
      ET is shown to follow a concerted dissociative mechanism that leads to the
      distonic radical anion, which is itself reduced in a second step by an overall
      two-electron process. The kinetics of homogeneous ET to these endoperoxides from
      an extensive series of radical anion electron donors were measured as a function
      of the driving force of electron transfer (deltaG(o)ET). The kinetics of
      heterogeneous ET were also studied by convolution analysis. Together, the
      heterogeneous and homogeneous ET kinetic data provide the best example of the
      parabolic nature of the activation-driving force relationship for a concerted
      dissociative ET described by Saveant; the data is particularly illustrative due
      to the low bond-dissociation enthalpy (BDE) of the O-O bond and hence small
      intrinsic barriers. Analysis of the data allowed the dissociative reduction
      potentials (E(o)diss) to be determined as -1.2 and -1.1 Vagainst SCE for ASC and
      DASC, respectively. Unusually low pre-exponential factors measured in temperature
      dependent kinetic studies suggest that ET to these O-O bonded systems is
      nonadiabatic. Analysis of ET kinetics for ASC and DASC by the Saveant model with
      a modification for nonadiabaticity allowed the intrinsic free energy for ET to be
      determined. The use of this approach and estimates for the BDE provide
      approximations of the reorganization energies. We suggest the methodology
      described herein can be used to evaluate the extent of ET to other endoperoxides
      of biological relevance and to provide thermochemical data not otherwise
      available.

PMID- 11596945
TI  - Spirocyclopropanated bicyclopropylidenes: straightforward preparation, physical
      properites, and chemical transformations.
AB  - Perspirocyclopropanated bicyclopropylidene (6) was prepared in three steps from 7
      cyclopropylidenedispiro[2.0.2.1]heptane (4) (24% overall) or, more efficiently,
      through dehalogenative coupling of 7,7-dibromo[3]triangulane (15) (82%). This
      type of reductive dimerization turned out to be successful for the synthesis of
      (E)- and (Z)-bis(spiropentylidene) 14 (67%) and even of the "third-generation"
      spirocyclopropanated bicyclopropylidene 17 (17% overall from 15). Whereas the
      parent bicyclopropylidene 1 dimerized at 180 degrees C to yield [4]rotane,
      dimerization of 6 at 130 degrees C under 10 kbar pressure occured only with
      opening of one three-membered ring to yield the polyspirocyclopropanated
      (cyclopropylidene)cyclopentane derivative 19 (34% yield), and at the elevated
      temperature the polyspirocyclopropanated 2-cyclopropylidene[3.2.2]propellane
      derivative 20 (25 % yield). Perspirocyclopropanated bicyclopropylidene 6 and the
      "third-generation" bicyclopropylidene 17 gave addition of bromine, hydrogen
      bromide, and various dihalocarbenes without rearrangement. The functionally
      substituted branched [7]triangulane 28 and branched dichloro-C2v-[15]triangulane
      32 were used to prepare the perspirocyclopropanated [3]rotane (D3h
      [10]triangulane) 49 (six steps from 6, 1.4% overall yield) and the C2v
      [15]triangulane 51 (two steps from 17, 41% overall). Upon catalytic
      hydrogenation, the perspirocyclopropanated bicyclopropylidene 6 yielded 7,7'
      bis(dispiro[2.0.2.]-heptyl) (52) and, under more forcing conditions, 1,1'
      bis(2,2,3,3-tetramethylcyclopropyl) (53). The bromofluorocarbene adduct 33 of 17
      reacted with butyllithium to give the unexpected polyspirocyclopropanated 1,4-di
      n-butyl-2-cyclopropylidenebicyclo[2.2.0]hexane derivative 37 as the main product
      (55% yield) along with the expected "third-generation" perspirocyclopropanated
      dicyclopropylidenemethane 38 (21% yield). Mechanistic aspects of this and the
      other unusual reactions are discussed. The structures of all new unusual
      hydrocarbons were proven by X-ray crystal structure analyses, and the most
      interesting structural and crystal packing features are presented.

PMID- 11596946
TI  - A one-pot sequence of Stille and Heck couplings: synthesis of various 1,3,5
      hexatrienes and their subsequent 6pi-electrocyclizations.
AB  - Palladium-catalyzed cross-coupling reactions of 2-bromocyclohex-1-enyl triflates
      7 and 11 with a variety of alkenylstannanes occurred chemoselectively at the site
      of the triflate leaving group to give bromobutadienes which readily underwent
      Heck reactions with acrylates and styrene. Both steps could be performed in the
      same flask to give differentially functionalized hexatrienes in up to 88% overall
      yield. With simple stannanes, the same catalyst precursor could be used for both
      coupling steps making it possible to perform the whole sequence with only one
      portion of catalyst. For some of the functionally substituted stannanes,
      specifically adjusted catalyst systems had to be used. The 1,3,5-hexatrienes
      obtained were further transformed, in particular the methoxy-substituted
      compounds 14a-c were converted to bicyclo[4.4.0]decenones 30 (71-97%),
      bicyclo[4.3.0]nonenones 35 (74-93%), cyclodecynone 37a (47%), and cyclononynone
      39a (15%). Thermal electrocyclizations of the other hexatrienes gave
      tetrahydronaphthalines 31 (60-61%), the tricyclic lactone 32 (72-75%) and
      decahydrophenanthrene 33 (75 %) in good yields.

PMID- 11596947
TI  - Cigarette smoking and death following subarachnoid hemorrhage.

PMID- 11596948
TI  - Influence of premorbid factors on survival following subarachnoid hemorrhage.
AB  - OBJECT: The goal of this study was to explore the relationships between premorbid
      patient characteristics, especially cigarette smoking, and the risk of death
      following subarachnoid hemorrhage (SAH). METHODS: A population-based study design
      was used with multiple overlapping methods of case identification. A strict
      definition of SAH was used. Relationships between patients' age and sex as well
      as their cigarette smoking and hypertension statuses were explored by calculating
      relative risks (RRs). Confounding effects were examined using logistic regression
      analysis. The author identified 800 cases in which the patient had experienced
      his or her first SAH. Seventy-seven percent of cases were verified by review of
      computerized tomography scans, 22% by autopsy, and 1% by lumbar puncture. A prior
      history of hypertension had no effect on the risk of mortality. There was a
      higher case mortality rate in female patients than in male patients, but this did
      not reach statistical significance. The RR of death at 30 days post-SAH for
      patients older than 60 years compared with those who were younger was 2.95 (95%
      confidence interval [CI] 2.18-3.97). The RR of death at all time intervals was
      lower for smokers than for nonsmokers (smokers/nonsmokers RR 0.47 [95% CI 0.32
      0.69] at 7 days). The protective effect of smoking diminished on Day 3 post-SAH
      and increased again on Day 7. CONCLUSIONS: Advanced age is an important
      determinant of survival following SAH. Smoking appears to have a protective
      effect. The author presents evidence indicating that increased vasospasm in
      smokers may reduce the severity of the initial hemorrhage.

PMID- 11596949
TI  - Adult respiratory distress syndrome: a complication of induced hypertension after
      severe head injury.
AB  - OBJECT: The factors involved in the development of adult respiratory distress
      syndrome (ARDS) after severe head injury were studied. The presence of ARDS
      complicates the treatment of patients with severe head injury, both because
      hypoxia causes additional injury to the brain and because therapies that are used
      to protect the lungs and improve oxygenation in patients with ARDS can reduce
      cerebral blood flow (CBF) and increase intracranial pressure (ICP). In a recent
      randomized trial of two head-injury management strategies (ICP-targeted and CBF
      targeted), a fivefold increase in the incidence of ARDS was observed in the CBF
      targeted group. METHODS: Injury severity, physiological data, and treatment data
      in 18 patients in whom ARDS had developed were compared with the remaining 171
      patients in the randomized trial in whom it had not developed. Logistic
      regression analysis was used to study the interaction of the factors that were
      related to the development of ARDS. In the final exact logistic regression model,
      several factors were found to be significantly associated with an increased risk
      of ARDS: administration of epinephrine (5.7-fold increased risk), administration
      of dopamine in a larger than median dose (10.8-fold increased risk), and a
      history of drug abuse (3.1-fold increased risk). CONCLUSIONS: Although this
      clinical trial was not designed to study the association of management strategy
      and the occurrence of ARDS, the data strongly indicated that induced hypertension
      in this high-risk group of patients is associated with the development of
      symptomatic ARDS.

PMID- 11596950
TI  - Hyperacute measurement of intracranial pressure, cerebral perfusion pressure,
      jugular venous oxygen saturation, and laser Doppler flowmetry, before and during
      removal of traumatic acute subdural hematoma.
AB  - OBJECT: The poor prognosis for traumatic acute subdural hematoma (ASDH) might be
      due to underlying primary brain damage, ischemia, or both. Ischemia in ASDH is
      likely caused by increased intracranial pressure (ICP) leading to decreased
      cerebral perfusion pressure (CPP), but the degree to which these phenomena occur
      is unknown. The authors report data obtained before and during removal of ASDH in
      five cases. METHODS: Five patients who underwent emergency evacuation of ASDH
      were monitored. In all patients, without delaying treatment, a separate surgical
      team (including the senior author) placed an ICP monitor and a jugular bulb
      catheter, and in two patients a laser Doppler probe was placed. The ICP prior to
      removing the bone flap in the five patients was 85, 85, 50, 59, and greater than
      40 mm Hg, resulting in CPPs of 25, 3, 25, 56, and less than 50 mm Hg,
      respectively. Removing the bone flap as well as opening the dura and removing the
      blood clot produced a significant decrease in ICP and an increase in CPP. Jugular
      venous oxygen saturation (SjvO2) increased in four patients and decreased in the
      other during removal of the hematoma. Laser Doppler flow also increased, to 217%
      and 211% compared with preevacuation flow. CONCLUSIONS: Intracranial pressure is
      higher than previously suspected and CPP is very low in patients with ASDH.
      Removal of the bone flap yielded a significant reduction in ICP, which was
      further decreased by opening the dura and evacuating the hematoma. The SjvO2 as
      well as laser Doppler flow increased in all patients but one immediately after
      removal of the hematoma.

PMID- 11596951
TI  - Surgical management and outcome in patients with radial nerve lesions.
AB  - OBJECT: The goal of this paper was to review surgical management and outcomes in
      patients treated for radial nerve (RN) lesions at Louisiana State University
      Health Sciences over a period of 30 years. METHODS: Two hundred sixty patients
      with RN injuries were evaluated. The most common mechanisms of injuries involving
      the RN included fracture of the humerus, laceration, blunt contusions, and
      gunshot wounds. One hundred and eighty patients (69%) underwent surgery. Lesions
      not in continuity required primary or secondary end-to-end suture repairs or
      graft repairs. With the use of direct intraoperative nerve action potential
      recording, RN injuries in which the lesion was in continuity required external or
      internal neurolysis or resection of the lesion followed by end-to-end suture or
      graft repair. A minimum of 1.5 years follow-up review was available in 90% of the
      patients who underwent surgery. Motor function recovery to Grade 3 or better was
      observed in 10 (91%) of 11 patients who underwent primary suture repair, 25 (83%)
      of 30 who underwent secondary suture repair, 43 (80%) of 54 who received graft
      repair, and 63 (98%) of 64 in whom neurolysis was performed. Sixteen (71%) of 21
      patients with superficial sensory RN injury achieved satisfactory pain relief
      after complete resection of a neuroma or neurolysis. CONCLUSIONS: This study
      clearly demonstrates that excellent functional recovery can be achieved with
      proper surgical management of RN injuries.

PMID- 11596952
TI  - Surgical management and outcomes in patients with median nerve lesions.
AB  - OBJECT: One hundred sixty-seven of 250 patients with median nerve (MN) lesions,
      excluding carpal tunnel syndrome and nerve sheath tumors, at the levels of the
      arm, elbow, forearm, and wrist, underwent surgical treatment at Louisiana State
      University Health Sciences over a 30-year period. The most common causes of MN
      injuries were laceration, fracture-associated stretch and contusion, gunshot
      wound, compression, and injection injuries. In this study, surgically treated
      patients were followed and evaluated retrospectively for favorable functional
      outcomes. METHODS: Lesions not in continuity required primary or secondary end-to
      end suture or graft repairs. With the aid of direct intraoperative recording of
      nerve action potentials (NAPs), MN injuries in which the lesion was in continuity
      underwent external or internal neurolysis, or resection of the lesion, followed
      by end-to-end suture or graft repair. A minimum of 12 months follow-up review
      (mean 18 months) was available in 85% of the surgically treated patients. For
      lesions in continuity, a functional recovery of Grade 3 or better was seen in 72
      (95%) of 76 patients who underwent neurolysis, 18 (86%) of 21 who received suture
      repair, and 21 (75%) of 28 who received graft repair. In lesions not in
      continuity, favorable results (Grade > or = 3) were seen in 10 (91%) of 11
      patients who received primary suture repair, seven (78%) of nine who received
      secondary suture repair, and 15 (68%) of 22 who received graft repair.
      CONCLUSIONS: Surgical intervention for MN injuries with complete or severe
      deficits achieved favorable outcomes.

PMID- 11596953
TI  - Risk factors affecting survival after brain metastases from non-small cell lung
      carcinoma: a follow-up study of 70 patients.
AB  - OBJECT: The authors present their experience with the treatment of brain
      metastases from non-small cell lung carcinoma (NSCLC). METHODS: A retrospective
      review was conducted in which records from 74 patients treated at the authors'
      institution between 1994 and 1999 were assessed. Survival and functional outcome
      were reviewed relative to individual patient variables. The median survival time
      was 12.9 months, with 1-, 2-, and 5-year survival milestones reached by 52.2%,
      30.7%. and 18.1% of patients, respectively. Patients were stratified into groups
      composed of those with synchronous brain metastases (tumors diagnosed within 3
      months of NSCLC) and metachronous brain metastases (tumors diagnosed 3 months
      after NSCLC). The median survival time and 5-year survival rate were 18 months
      and 28.9% for metachronous, compared with 9.9 months and 0% for synchronous brain
      metastases. In univariate analyses, the stage of brain metastases, an initial
      Karnofsky Performance Scale (KPS) score of 90 or less, and conservative therapy
      for NSCLC were associated with worse outcomes (p < 0.05). In analyses in which
      tumors were stratified by synchronous compared with metachronous brain
      metastases, a preoperative KPS score of 90 or less and radiation therapy (RT)
      alone for brain metastases were associated with worse outcomes in patients with
      metachronous brain metastases but not with synchronous tumors (p < 0.05). When
      stratified by preoperative KPS score, the synchronous brain metastases stage or
      treatment of brain metastases with RT alone were associated with worse outcome in
      patients with KPS scores of 100, but had no discernible effect on patients with
      KPS scores of 90 or less (p < 0.05). CONCLUSIONS: The tumor stage and
      preoperative KPS score were significantly associated with survival. Craniotomy
      plus RT significantly improved the prognosis in patients with metachronous brain
      metastases or those with a preoperative KPS score of 100.

PMID- 11596954
TI  - Predictive value of progression-associated chromosomal aberrations for the
      prognosis of meningiomas: a retrospective study of 198 cases.
AB  - OBJECT: The goal of this study was to determine whether in meningiomas
      cytogenetic findings are suitable as a predictive parameter relevant to
      prognosis. METHODS: Between 1992 and 1998 at the Department of Neurosurgery,
      Saarland University, 198 patients underwent surgery to resect meningiomas. The
      meningiomas were investigated cytogenetically and the patients were followed up
      for a mean period of 33 months. On the basis of the cytogenetic findings, the
      meningiomas were subdivided into four groups: Group 0 meningiomas displayed a
      normal diploid chromosome set; Group 1 tumors were found to have monosomy 22 as
      the sole cytogenetic aberration; Group 2 tumors were markedly hypodiploid
      meningiomas with loss of additional autosomes in addition to monosomy 22; and
      Group 3 meningiomas had deletions of the short arm of a chromosome 1, as well as
      additional chromosomal aberrations including loss of one chromosome 22. One
      hundred ninety-eight patients in whom tumor resections were determined to be
      Simpson Grade I or II could be followed up after complete tumor extirpation. In
      20 patients, one or several recurrences were documented during the period of
      observation. The tumors were classified according to their different, but mostly
      uniform chromosomal aberrations. Recurrences were found in six (4.3%) of 139
      tumors in Groups 0 and 1 and in two (10.5%) of 19 tumors in Group 2; the highest
      rate of recurrence was found in 12 (30%) of 40 tumors in Group 3. This supports
      the notion that the deletion of the short arm of one chromosome 1 is an important
      prognostic factor in meningiomas. The results of this study document a
      significant correlation between histological grade (p < 0.0001), location (p <
      0.0001), and recurrences of meningiomas (p < 0.0001) (significance determined
      using chi-square tests). CONCLUSIONS: The cytogenetic classification of
      meningiomas provides a significant contribution to the predictability of tumor
      recurrence and is, therefore, a valuable criterion for the neurosurgeon's
      postoperative management protocol.

PMID- 11596955
TI  - Monitoring of intraoperative motor evoked potentials to increase the safety of
      surgery in and around the motor cortex.
AB  - OBJECT: The repetitive application of high-frequency anodal monopolar stimulation
      during surgery in or near the motor cortex allows a qualitative and quantitative
      evaluation of motor evoked potentials (MEPs). Using this method, motor pathways
      and motor function can be continuously monitored during surgery. METHODS: In this
      prospective study, 70 patients underwent MEP monitoring during surgery performed
      in the central region. All procedures were performed after general anesthesia had
      been induced without the aid of muscle relaxants. The motor pathways were
      monitored during the entire surgical procedure by repetitive high-frequency
      anodal monopolar stimulation (frequency 400-500 Hz; train 7-10 pulses; impulse
      duration 0.2-0.7 msec; and stimulation intensity 16.9 +/- 7.76 mA). The MEPs were
      continuously evaluated to assess their latency, potential duration, and
      amplitude. Recorded alterations in these parameters were subsequently correlated
      with surgical maneuvers and with postoperative neurological deterioration. The
      monitoring parameters (latency, potential duration, and amplitude) had a broad
      interindividual range of variation. A correlation between individual
      intraoperative changes in the potentials and surgical maneuvers or postoperative
      neurological deterioration was observed in eight cases. A spontaneous shift in
      latency greater than 15% or a sudden reduction in the amplitude of the potential
      greater than 80% was considered a warning criterion. In all cases in which there
      was an irreversible change in latency or a complete loss of potentials were
      observed, there was postoperative neurological deterioration. CONCLUSIONS:
      Improved surgical safety can be achieved using intraoperative neurophysiological
      monitoring procedures. Repetitive stimulation of the motor cortex proved to be a
      reliable method for monitoring subcortical motor pathways. Changes in MEP latency
      and MEP amplitude served as warning criteria during surgery and possessed
      prognostic value.

PMID- 11596956
TI  - Strategies for reoperation after comprehensive epilepsy surgery.
AB  - OBJECT: Prior reports of seizure control following reoperation for failed
      epilepsy surgery have shown good results. These studies included patients who
      presented during the era preceding magnetic resonance (MR) imaging, and the
      patients were often not monitored intracranially or underwent subtotal
      hippocampal resections. In this study, the authors hypothesized that reoperation
      for recurrent seizures following a more comprehensive initial workup and surgery
      would not yield such good results. METHODS: The authors examined a consecutive
      series of patients who underwent two operations at Yale-New Haven Hospital for
      medically intractable epilepsy and in whom there was a minimum of 1-year follow
      up after the second surgery. All patients were evaluated and treated according to
      a standard protocol, including preoperative MR imaging, a low threshold for
      invasive monitoring, and a radical amygdalohippocampectomy when indicated. Twenty
      seven patients were identified (five with mesial temporal sclerosis, 20 with
      neocortical disease, and two with multifocal sites of seizure onset) of whom six
      (22%) underwent intentionally palliative second surgery (corpus callostomy or
      placement of a vagus nerve stimulator [VNS]). Of the remaining 21 patients, only
      four (19%) became seizure free after a second resective operation. The most
      common causes of treatment failure were dual pathology, recurrent tumor, limited
      resection to preserve function, widespread developmental abnormalities, and
      electrographic sampling error. Successful outcomes resulted from removal of
      recurrent tumors, completion of a functional hemispherectomy, or repeated
      invasive monitoring to correct a sampling error. Five (83%) of the six
      intentionally palliative second operations resulted in more than a 50% decrease
      in seizure frequency. CONCLUSIONS: If an aggressive preoperative evaluation and
      surgical resection are performed, reoperation for recurrent seizures has a much
      lower likelihood of cure than previously reported. Intentionally palliative
      surgery such as placement of a VNS unit may be considered for patients in whom
      the initial operation fails to decrease seizure frequency.

PMID- 11596957
TI  - Endovascular treatment of basilar artery trunk aneurysms with Guglielmi
      detachable coils: clinical experience with 41 aneurysms in 39 patients.
AB  - OBJECT: The authors present a retrospective analysis of their clinical experience
      in the endovascular treatment of basilar artery (BA) trunk aneurysms with
      Guglielmi detachable coils (GDCs). METHODS: Between April 1990 and June 1999,41
      BA trunk aneurysms were treated in 39 patients by inserting GDCs. Twenty-seven
      patients presented with subarachnoid hemorrhage, six had intracranial mass
      effect, and in six patients the aneurysms were found incidentally. Eighteen
      lesions were BA trunk aneurysms, 13 were BA-superior cerebellar artery aneurysms,
      four were BA-anterior inferior cerebellar artery aneurysms, and six were
      vertebrobasilar junction aneurysms. Thirty-five patients (89.7%) had excellent or
      good clinical outcomes; procedural morbidity and mortality rates were 2.6% each.
      Thirty-six aneurysms were selectively occluded while preserving the parent
      artery, and in five cases the parent artery was occluded along with the aneurysm.
      Immediate angiographic studies revealed complete or nearly complete occlusion in
      35 aneurysms (85.4%). Follow-up angiograms were obtained in 29 patients with 31
      aneurysms: the mean follow-up period was 17 months. No recanalization was
      observed in the eight completely occluded aneurysms. In 19 lesions with small
      neck remnants, seven (36.8%) had further thrombosis, three (15.8%) remained
      anatomically unchanged, and nine (47.3%) had recanalization caused by coil
      compaction. In one patient (2.6%) the aneurysm rebled 8 years after the initial
      embolization. CONCLUSIONS: In this clinical series the authors show that the GDC
      placement procedure is valuable in the therapeutic management of BA trunk
      aneurysms. The endovascular catheterization of these lesions tends to be
      relatively simple, in contrast with more complex neurosurgical approaches.
      Endosaccular obliteration of these aneurysms also decreases the possibility of
      unwanted occlusion of perforating arteries to the brainstem.

PMID- 11596958
TI  - Population-based analysis of arteriovenous malformation treatment.
AB  - OBJECT: The author sought to describe overall management data on cerebral
      arteriovenous malformations (AVMs) and to focus the actuarial need for different
      treatment modalities on a population-based scale. Such data would seem important
      in the planning of regional or national multimodality strategies for the
      treatment of AVMs. This analysis of a nonselected, consecutive series of patients
      representing every diagnosed case of cerebral AVM in a population of 1,000,000
      over one decade may serve to shed some light on these treatment aspects. METHODS:
      During the 11-year period from 1989 to 1999, data from every patient harboring a
      cerebral AVM that was presented clinically or discovered incidentally in a
      strictly defined population of 986,000 people were collected prospectively. No
      patient was lost to follow up. There were 12.4 de novo diagnosed AVMs per
      1,000,000 population per year (135 AVMs). Large high-grade AVMs (Spetzler-Martin
      classification) were rare, and Grade 1 to 3 lesions represented 85% of the
      caseload. Hemorrhage was the initial manifestation of AVM in 69.6% of the cases.
      lntracerebral hematoma was the most common hemorrhagic manifestation occurring in
      78 patients. There were 4.4 cases per 1,000,000 population per year of hematomas
      needing expedient surgical evacuation. In the remaining patients who did not
      require hematoma surgery, small, critically located Grade 3 and Grade 4 lesions
      amounted to 1.6 cases per 1,000,000 population per year. There were 5.8 cases per
      1,000,000 population per year of Grade 1 to 2 and larger noncritically located
      Grade 3 malformations. There were 0.5 cases per 1,000,000 population per year of
      Grade 5 AVMs. The overall outcome in 135 patients was classified as good
      according to the Glasgow Outcome Scale (Score 5) in 61% of the cases, and the
      overall mortality rate was 9%. CONCLUSIONS: In centers with population-based
      referral, AVM of the brain is predominantly a disease related to intracranial
      bleeding. and parenchymal clots have a profound impact on overall management
      outcome. The rupture of an AVM is as devastating as that of an aneurysm. Aneurysm
      ruptures are more lethal, whereas AVM rupture tends to result in more
      neurological disability due to the high occurrence of lobar intracerebral
      hematoma. In an attempt to quantify the need for different modalities of AVM
      treatment based on a population of 1,000,000 people, figures for surgeries
      performed range from six to 10 operations per year and embolization as well as
      gamma knife surgery procedures range from two to seven per year, depending on the
      strategy at hand. When using nonsurgical approaches to Grade 1 to 3 lesions, the
      number of patients requiring treatment with more than one method for obliteration
      increases drastically as does the potential risk for procedure-related
      complications.

PMID- 11596959
TI  - Surgical resection of intrinsic insular tumors: complication avoidance.
AB  - OBJECT: Surgical resection of tumors located in the insular region is challenging
      for neurosurgeons, and few have published their surgical results. The authors
      report their experience with intrinsic tumors of the insula, with an emphasis on
      an objective determination of the extent of resection and neurological
      complications and on an analysis of the anatomical characteristics that can lead
      to suboptimal outcomes. METHODS: Twenty-two patients who underwent surgical
      resection of intrinsic insular tumors were retrospectively identified. Eight
      tumors (36%) were purely insular, eight (36%) extended into the temporal pole,
      and six (27%) extended into the frontal operculum. A transsylvian surgical
      approach, combined with a frontal opercular resection or temporal lobectomy when
      necessary, was used in all cases. Five of 13 patients with tumors located in the
      dominant hemisphere underwent craniotomies while awake. The extent of tumor
      resection was determined using volumetric analyses. In 10 patients, more than 90%
      of the tumor was resected; in six patients, 75 to 90% was resected; and in six
      patients, less than 75% was resected. No patient died within 30 days after
      surgery. During the immediate postoperative period, the neurological conditions
      of 14 patients (64%) either improved or were unchanged, and in eight patients
      (36%) they worsened. Deficits included either motor or speech dysfunction. At the
      3-month follow-up examination, only two patients (9%) displayed permanent
      deficits. Speech and motor dysfunction appeared to result most often from
      excessive opercular retraction and manipulation of the middle cerebral artery
      (MCA), interruption of the lateral lenticulostriate arteries (LLAs), interruption
      of the long perforating vessels of the second segment of the MCA (M2), or
      violation of the corona radiata at the superior aspect of the tumor. Specific
      methods used to avoid complications included widely splitting the sylvian fissure
      and identifying the bases of the periinsular sulci to define the superior and
      inferior resection planes, identifying early the most lateral LLA to define the
      medial resection plane, dissecting the MCA before tumor resection, removing the
      tumor subpially with preservation of all large perforating arteries arising from
      posterior M2 branches, and performing craniotomy with brain stimulation while the
      patient was awake. CONCLUSIONS: A good understanding of the surgical anatomy and
      an awareness of potential pitfalls can help reduce neurological complications and
      maximize surgical resection of insular tumors.

PMID- 11596960
TI  - Analysis of loss of heterozygosity on chromosome 10 in patients with malignant
      astrocytic tumors: correlation with patient age and survival.
AB  - OBJECT: The most frequent genetic abnormality in human malignant gliomas is loss
      of heterozygosity (LOH) on chromosome 10. Candidate genes on chromosome 10 that
      are associated with the prognosis of patients with anaplastic astrocytoma (AA)
      and glioblastoma (GBM) were evaluated. METHODS: The authors used 12 fluorescent
      microsatellite markers on both arms of chromosome 10 to study LOH in 108 primary
      astrocytic tumors. The LOH on chromosome 10 was observed in 11 (32%) of 34 AAs
      and 34 (56%) of 61 GBMs. No LOH was detected in 13 low-grade gliomas. Loss of
      heterozygosity was not detected in any AA in the seven patients younger than 35
      years, but it was discovered in 41% of the patients older than 35 years. The
      prognostic significance of LOH at each locus was evaluated in 89 patients older
      than 15 years; 33 (37%) had supratentorial AAs and 56 (63%) had supratentorial
      GBMs. The Cox proportional hazards model, adjusted for patient age at surgery,
      the preoperative Karnofsky Performance Scale score, and the extent of surgical
      resection revealed that LOH on marker D10S209 near the FGFR2 and DMBT1 genes was
      significantly associated with shorter survival in patients with AA. The LOH on
      markers D10S215 and D10S541, which contain the PTEN/MMAC1 gene between them, was
      significantly associated with shorter survival in patients with GBM. CONCLUSIONS:
      In the present study it is found that LOH on chromosome 10 is an age-dependent
      event for patients with AAs and that LOH on marker D10S209 near the FGFR2 and
      DMBT1 loci is a significantly unfavorable prognostic factor. It is also reported
      that LOH on the PTEN/MMAC1 gene is a significantly unfavorable prognostic factor
      in patients with GBM.

PMID- 11596961
TI  - Negative autoregulation of fibroblast growth factor receptor 2 expression
      characterizing cranial development in cases of Apert (P253R mutation) and
      Pfeiffer (C278F mutation) syndromes and suggesting a basis for differences in
      their cranial phenotypes.
AB  - OBJECT: Heterogeneous mutations in the fibroblast growth factor receptor 2 gene
      (FGFR2) cause a range of craniosynostosis syndromes. The specificity of the Apert
      syndrome-affected cranial phenotype reflects its narrow mutational range: 98% of
      cases of Apert syndrome result from an Ser252Trp or Pro253Arg mutation in the
      immunoglobulin-like (Ig)IIIa extracellular subdomain of FGFR2. In contrast, a
      broad range of mutations throughout the extracellular domain of FGFR2 causes the
      overlapping cranial phenotypes of Pfeiffer and Crouzon syndromes and related
      craniofacial dysostoses. METHODS: In this paper the expression of FGFR1, the
      IgIIIa/c and IgIIIa/b isoforms of FGFR2, and FGFR3 is investigated in Apert
      syndrome (P253R mutation)- and Pfeiffer syndrome (C278F mutation)-affected fetal
      cranial tissue and is contrasted with healthy human control tissues. Both FGFR1
      and FGFR3 are normally expressed in the differentiated osteoblasts of the
      periosteum and osteoid, in domains overlapped by that of FGFR2, which widely
      include preosseous cranial mesenchyme. Expression of FGFR2, however, is
      restricted to domains of advanced osseous differentiation in both Apert syndrome-
      and Pfeiffer syndrome-affected cranial skeletogenesis in the presence of
      fibroblast growth factor (FGF)2, but not in the presence of FGF4 or FGF7. Whereas
      expression of the FGFR2-IgIIIa/b (KGFR) isoform is restricted in normal human
      cranial osteogenesis, there is preliminary evidence that KGFR is ectopically
      expressed in Pfeiffer syndrome-affected cranial osteogenesis. CONCLUSIONS:
      Contraction of the FGFR2-IgIIIa/c (BEK) expression domain in cases of Apert
      syndrome- and Pfeiffer syndrome-affected fetal cranial ossification suggests that
      the mutant activation of this receptor, by ligand-dependent or ligand-independent
      means, results in negative autoregulation. This phenomenon, resulting from
      different mechanisms in the two syndromes, offers a model by which to explain
      differences in their cranial phenotypes.

PMID- 11596962
TI  - Protective effects of glial cell line-derived neurotrophic factor on hippocampal
      neurons after traumatic brain injury in rats.
AB  - OBJECT: The purpose of this study was to evaluate whether glial cell line-derived
      neurotrophic factor (GDNF) can protect against hippocampal neuronal death after
      traumatic brain injury (TBI). METHODS: Male Sprague-Dawley rats were subjected to
      moderate TBI with a controlled cortical impact device while in a state of
      halothane-induced anesthesia. Then, GDNF or artificial cerebrospinal fluid
      ([aCSF]; vehicle) was infused into the frontal horn of the left lateral
      ventricle. In eight brain-injured and eight sham-operated rats, GDNF was infused
      continuously for 7 days (200 ng/day intracerebroventricularly at a rate of 8.35
      ng/0.5 microl/hour). An equal volume of vehicle was infused at the same rate into
      the remaining eight brain-injured and eight sham-operated rats. Seven days post
      injury, all rats were killed. Their brains were sectioned and stained with cresyl
      violet, and the hippocampal neuronal loss was evaluated in the CA2 and CA3
      regions with the aid of microscopy. A parallel set of sections from each brain
      was subjected to immunoreaction with antibodies against glial fibrillary acidic
      protein (GFAP; astroglia marker). In the aCSF-treated group, TBI resulted in a
      significant neuronal loss in the CA2 (60%, p < 0.05) and CA3 regions (68%, p <
      0.05) compared with the sham-operated control animals. Compared with control rats
      infused with aCSF, GDNF infusion significantly decreased the TBI-induced neuronal
      loss in both the CA2 (58%, p < 0.05) and CA3 regions (51%, p < 0.05). There was
      no difference in the number of GFAP-positive astroglial cells in the GDNF-infused
      rats in the TBI and sham-operated groups compared with the respective vehicle
      treated groups. CONCLUSIONS: The authors found that GDNF treatment following TBI
      is neuroprotective.

PMID- 11596963
TI  - Attenuation of intracerebral hemorrhage and thrombin-induced brain edema by
      overexpression of interleukin-1 receptor antagonist.
AB  - OBJECT: Adenovirus-mediated overexpression of interleukin-1 receptor antagonist
      (IL-1ra) attenuates the inflammatory reaction and brain injury that follows focal
      cerebral ischemia. Recently, an inflammatory reaction after intracerebral
      hemorrhage (ICH) was identified. In this study the authors examine the hypothesis
      that overexpression of IL-1ra reduces brain injury (specifically edema formation)
      after ICH. METHODS: Adenoviruses expressing IL-1ra (Ad.RSVIL-1ra) or LacZ, a
      control protein (Ad.RSVlacZ), or saline were injected into the left lateral
      cerebral ventricle in rats. On the 5th day after virus injection, 100 microl of
      autologous blood or 5 U thrombin was infused into the right basal ganglia. Rats
      with ICH were killed 24 or 72 hours later for measurement of brain water and ion
      content. Thrombin-treated rats were killed 24 hours later for edema measurements
      and an assessment of polymorphonuclear leukocyte (PMNL) infiltration by
      myeloperoxidase (MPO) assay, as well as histological evaluation. Compared with
      saline-treated and Ad.RSVlacZ-transduced controls, Ad.RSVIL-1ra-transduced rats
      had significantly attenuated edema in the ipsilateral basal ganglia 3 days after
      ICH (81.5 +/- 0.3% compared with 83.4 +/- 0.4% and 83.3 +/- 0.5% in control
      animals). Thrombin-induced brain edema was also reduced in Ad.RSVIL-1ra-treated
      rats (81.3 +/- 0.4% compared with 83.2 +/- 0.4% and 82.5 +/- 0.4% in control
      rats). The reduction in thrombin-induced edema was associated with a reduction in
      PMNL infiltration into the basal ganglia, as assessed by MPO assay (49%
      reduction) and histological examination. CONCLUSIONS: Overexpression of IL-1ra by
      using an adenovirus vector attenuated brain edema formation and thrombin-induced
      intracerebral inflammation following ICH. The reduction in ICH-induced edema with
      IL-1ra may result from reduction of thrombin-induced brain inflammation.

PMID- 11596964
TI  - Effect of absorbable topical hemostatic agents on the relaxation time of blood:
      an in vitro study with implications for postoperative magnetic resonance imaging.
AB  - OBJECT: Absorbable topical hemostatic agents are commonly used in neurosurgery.
      In this study the authors examine the longitudinal relaxation time (T1) of blood
      in contact with these agents over time, measured in vitro, to determine if their
      presence could affect the interpretation of postoperative magnetic resonance (MR)
      images. METHODS: Coagulated and anticoagulated blood were used, both oxygenated
      and deoxygenated. The effects of a collagen-based agent (Collastat) and a
      cellulose-based agent (Surgicel) on the pH and T1 values of blood and on those of
      saline (used as a control) were investigated. The T1 was measured as a function
      of magnetic field strength and time by using a field-cycling relaxometer. This
      instrument measures 1/T1, the rate of T1, from which the T, value is computed.
      The T1 values of blood were compared with those of hemostat-induced blood clots
      and with those of both gray and white matter of the brain. Signal changes on T1
      weighted MR images were predicted on the basis of altered T, values in vitro.
      Postoperative images were visually examined for the predicted changes. With the
      addition of Surgicel, blood had decreased pH and significantly shortened T1 at
      all fields, essentially within minutes, although it affected the T1 of saline
      only minimally. The effect of Surgicel increasingly shortened the T1 for 4 days
      in oxygenated blood. Collastat had no significant effect. The presence of some
      paramagnetic methemoglobin in Surgicel-induced clots was demonstrated using the
      relaxometer at a time when diamagnetic oxyhemoglobin would be present in
      naturally occurring blood clots. A bright signal that could mimic residual tumor
      on contrast-enhanced images was predicted and confirmed on postoperative T1
      weighted MR images obtained in patients in whom Surgicel lined the tumor bed. It
      was not present in cases in which Surgicel was not used. CONCLUSIONS: Surgicel
      alters the appearance of early postoperative MR images. To avoid
      misinterpretation, clinicians should be aware of this phenomenon.

PMID- 11596965
TI  - Laser, fibrin glue, or suture repair of peripheral nerves: a comparative
      functional, histological, and morphometric study in the rat sciatic nerve.
AB  - OBJECT: This study was undertaken to evaluate CO2 laser-assisted nerve repair and
      compare it with nerve repair performed with fibrin glue or absorbable sutures.
      METHODS: In eight rats, the sciatic nerve was sharply transected and approximated
      using two 10-0 absorbable sutures and then fused by means of CO2 milliwatt laser
      welding (power 100 mW, exposure time 1 second per pulse, spot size 320 microm),
      with the addition of a protein solder (bovine albumin) to reinforce the repair
      site. The control groups consisted of eight rats in which the nerves were
      approximated with two 10-0 absorbable sutures and subsequently glued using a
      fibrin sealant (Tissucol), and eight rats in which the nerves were repaired using
      conventional microsurgical sutures (four to six 10-0 sutures in the perineurium
      or epineurium). Evaluation was performed 16 weeks postsurgery and included the
      toe-spreading test and light microscopy and morphometric assessment. The motor
      function of the nerves in all groups showed gradual improvement with time. At 16
      weeks, the motor function was approximately 60% of the normal function, and there
      were no significant differences among the groups. On histological studies, all
      nerves revealed various degrees of axonal regeneration, with myelinated fibers in
      the distal nerve segments. There were slight differences in favor of the group
      treated with laser repair, in terms of wound healing at the repair site. In all
      groups, the number of axons distal to the repair site was higher compared with
      those proximal, but the axon diameter was significantly less than that in control
      nerves (p < 0.05). There were no significant differences in the number, density,
      or diameter of the axons in the proximal or distal nerve segments among the three
      nerve repair groups (p < 0.05), although there was a trend toward more and
      thicker myelinated axons in the distal segments of the laser-repaired nerves.
      CONCLUSIONS: It was found that CO2 laser-assisted nerve repair with soldering is
      at least equal to fibrin glue and suture repair in effectiveness in a rodent
      model of sciatic nerve repair.

PMID- 11596966
TI  - Cerebellar liponeurocytoma. Case report and review of the literature.
AB  - Cerebellar liponeurocytoma is a rare tumor of the posterior fossa that has many
      morphological similarities to medulloblastoma and neurocytoma. Recently the World
      Health Organization working group for classification of central nervous system
      neoplasms adopted the term "cerebellar liponeurocytoma" to provide a unified
      nomenclature for a tumor variously labeled in the literature as lipomatous
      medulloblastoma, lipidized medulloblastoma, medullocytoma. neurolipocytoma,
      lipomatous glioneurocytoma, and lipidized mature neuroectodermal tumor of the
      cerebellum. The rarity of this tumor and paucity of pertinent information
      regarding its biological potential and natural history have resulted in the
      application of various treatment modalities. It is suggested in the available
      literature that these lesions have a much more favorable prognosis than typical
      medulloblastomas, and that adjuvant therapy for liponeurocytoma need not be as
      extensive as that administered for medulloblastomas.

PMID- 11596967
TI  - Compressive optic neuropathy caused by renal osteodystrophy. Case report.
AB  - Compressive optic neuropathy with acute or chronic vision loss has been
      associated with various skull base tumors, aneurysms, Graves disease, trauma,
      and, less commonly, fibrous dysplasia and osteopetrosis. The authors present a
      case of acute visual deterioration in a 25-year-old woman who had massive
      calvarial hypertrophy with optic canal stenosis secondary to renal osteodystrophy
      (uremic leontiasis ossea [ULO]: bighead disease). Significant visual field
      restoration was achieved with high-dose corticosteroids followed by optic nerve
      decompression. This is the first case report of cranial neuropathy associated
      with ULO.

PMID- 11596968
TI  - Radiosurgery-induced brain tumor. Case report.
AB  - The authors describe a case of glioblastoma multiforme (GBM) associated with
      previous gamma knife radiosurgery for a cerebral arteriovenous malformation
      (AVM). A 14-year-old boy had undergone radiosurgery for an AVM, which was
      performed using a 201-source 60Co gamma knife system at another institution. The
      maximum and margin radiation doses used in the procedure were 40 and 20 Gy,
      respectively. One year after radiosurgery, the patient noticed onset of mild left
      hemiparesis due to radiation necrosis. Six and one-half years after radiosurgery,
      at the age of 20 years, the patient experienced an attack of generalized tonic
      clonic seizure. Magnetic resonance (MR) imaging revealed the existence of a brain
      tumor in the right parietal lobe. The patient underwent an operation and the
      histological diagnosis of the lesion was GBM. Ten months following the operation,
      that is, 99 months postradiosurgery, this patient died. To the best of the
      authors' knowledge, this is the first reported case of a neoplasm induced by
      radiosurgery for an AVM and the second case in which it occurred following
      radiosurgery for intracranial disease.

PMID- 11596969
TI  - Eyebrow incision for combined orbital osteotomy and supraorbital minicraniotomy:
      application to aneurysms of the anterior circulation. Technical note.
AB  - A modification of the supraorbital keyhole approach, the eyebrow incision
      minisupraorbital craniotomy with orbital osteotomy, is described. Unique to this
      approach is a one-piece supraorbital craniotomy, measuring 2.5 x 3.5 cm, that
      incorporates the orbital rim and roof and the frontal process of the zygomatic
      bone through an eyebrow incision. The orbital osteotomy facilitates view of the
      anterior and middle cranial fossa through the operating microscope, as well as
      the maneuverability of instruments through a small craniotomy. A pericranial flap
      is elevated with its base at the orbit and used for closure of the frontal sinus,
      if necessary. The approach was used successfully in elective surgery of 10
      aneurysms of the anterior circulation. The mean aneurysm size was 5.9 mm, with a
      range of 4 to 10 mm. Advantages of this approach include minimal disruption and
      exposure of normal brain tissue, reduced frontal lobe retraction, and an
      excellent postoperative cosmetic result. The approach is performed quickly by
      virtue of a limited skin incision with minimal temporalis muscle dissection and a
      small bone flap. The neuroendoscope, although helpful at times, is not essential
      and no special instruments or intraoperative image guidance is required. Relative
      contraindications include the presence of a large frontal sinus, severe brain
      edema, and recent subarachnoid hemorrhage. In addition, this approach has not
      been used for the treatment of giant intracranial aneurysms.

PMID- 11596970
TI  - Drop metastasis from pituitary adenoma. Case illustration.

PMID- 11596971
TI  - Traumatic aneurysm resulting from insertion of an intracranial pressure monitor.
      Case illustration.

PMID- 11596972
TI  - Contamination of glioblastoma multiforme with type 1 herpes simplex virus. Case
      illustration.

PMID- 11596973
TI  - Clip slippage.

PMID- 11596974
TI  - Subdural hematoma.

PMID- 11596975
TI  - Tay-Sachs disease: from clinical description to molecular defect.

PMID- 11596976
TI  - Molecular genetics of the beta-hexosaminidase isoenzymes: an introduction.

PMID- 11596977
TI  - Barney Sachs and the history of the neuropathologic description of Tay-Sachs
      disease.

PMID- 11596978
TI  - Cloning the beta-hexosaminidase genes.

PMID- 11596979
TI  - The search for the genetic lesion in Ashkenazi Jews with Classic Tay-Sachs
      disease.

PMID- 11596980
TI  - The beta-hexosaminidase story in Toronto: from enzyme structure to gene mutation.

PMID- 11596981
TI  - Biosynthesis of normal and mutant beta-hexosaminidases.

PMID- 11596982
TI  - Recognition and delineation of beta-hexosaminidase alpha-chain variants: a
      historical and personal perspective.

PMID- 11596983
TI  - Late-onset GM2 gangliosidosis and other hexosaminidase mutations among Jews.

PMID- 11596984
TI  - Naturally occurring mutations in GM2 gangliosidosis: a compendium.

PMID- 11596985
TI  - Targeting the hexosaminidase genes: mouse models of the GM2 gangliosidoses.

PMID- 11596986
TI  - Molecular epidemiology of Tay-Sachs disease.

PMID- 11596987
TI  - Early epidemiologic studies of Tay-Sachs disease.

PMID- 11596988
TI  - Screening and prevention in Tay-Sachs disease: origins, update, and impact.

PMID- 11596989
TI  - Not preventing--yet, just avoiding Tay-Sachs disease.

PMID- 11596990
TI  - Experiences in molecular-based prenatal screening for Ashkenazi Jewish genetic
      diseases.
AB  - Multiple-option prenatal carrier testing in the Ashkenazi Jewish community for
      three and now eight disorders has been readily accepted in this prenatal, health
      oriented and knowledgeable population. Counseling of screenees concerning the
      nature (severity, treatability, etc.), inheritance, and frequencies of each
      disorder was essential for informed test choices and future reproductive decision
      making. The value of couple testing for a group of disorders when 1 in about 6
      would be found to be a carrier of at least one disease was emphasized. These
      studies identified issues of education, confidentiality, posttest anxiety, and
      self-esteem that must be continuously addressed in the Ashkenazi population.
      However, an important value of these studies is that they provide a framework for
      the development of mass carrier screening programs in the general population or
      in specific segments of the population with similar demographic characteristics
      and in more diverse prenatal populations.

PMID- 11596991
TI  - The Dor Yeshorim story: community-based carrier screening for Tay-Sachs disease.

PMID- 11596992
TI  - Tay-Sachs disease and preimplantation genetic diagnosis.

PMID- 11596993
TI  - Treatment of GM2 gangliosidosis: past experiences, implications, and future
      prospects.

PMID- 11596994
TI  - Identification of the accumulated ganglioside.

PMID- 11596995
TI  - Tay-Sachs disease: psychologic care of carriers and affected families.

PMID- 11596996
TI  - Future perspectives for Tay-Sachs disease.

PMID- 11596997
TI  - Discovery of the hexosaminidase isoenzymes.

PMID- 11596998
TI  - Tay-Sachs disease: the search for the enzymatic defect.

PMID- 11596999
TI  - Discovery of beta-hexosaminidase A deficiency in Tay-Sachs disease.

PMID- 11597000
TI  - The GM2-gangliosidoses and the elucidation of the beta-hexosaminidase system.

PMID- 11597001
TI  - Subunit structure of the hexosaminidase isozymes.

PMID- 11597002
TI  - Cytoskeleton-dependent transport and localization of mRNA.
AB  - Messenger RNAs are localized in both somatic and germ cells as a means of
      focusing the translation of proteins at specific cellular sites. The signals for
      this lie within the mRNA, and these are recognized by proteins in the cell. The
      latter appear to be attached via linker proteins to the transport machinery for
      localization. In some instances it is a myosin motor which translocates along
      actin microfilaments, and in others kinesin or dynein motors appear to be
      responsible for driving the movement of mRNA along microtubule substrates. The
      way that cytoskeleton-based mRNA translocation is regulated is speculated upon.

PMID- 11597003
TI  - Plasticity and stabilization of neuromuscular and CNS synapses: interactions
      between thrombin protease signaling pathways and tissue transglutaminase.
AB  - The first association of the synapse as a potential site of neurodegenerative
      disease burden was suggested for Alzheimer's disease (AD) almost 30 years ago.
      Since then protease:protease inhibitor (P:PI) systems were first linked to
      functional regulation of synaptogenesis and synapse withdrawal at the
      neuromuscular junction (NMJ) more than 20 years ago. Confirmatory evidence for
      the involvement of the synapse, the rate-limiting or key unit in neural function,
      in AD did not become clear until the beginning of the 1990s. However, over the
      past 15 years evidence for participation of thrombin, related serine proteases
      and neural PIs, homologous and even identical to those of the plasma clot
      cascade, has been mounting. Throughout development a balance between
      stabilization forces, on the one hand, and breakdown influences, on the other,
      becomes established at synaptic junctions, just as it does in plasma clot
      proteins. The formation of protease-resistant cross-links by the transglutaminase
      (TGase) family of enzymes may add to the stability for this balance. The TGase
      family includes coagulation factor XIIIA and 8 other different genes, some of
      which may also influence the persistence of neural connections. Synaptic location
      of protease-activated, G-protein-coupled receptors (PARs) for thrombin and
      related proteases, their serpin and Kunitz-type PIs such as protease nexin I
      (PNI), alpha1-antichymotrypsin (alpha-ACT), and the Kunitz protease inhibitor
      (KPI)-containing secreted forms of beta-amyloid protein precursor (beta-APP),
      along with the TGases and their putative substrates, have all been amply
      documented. These findings strongly add to the conclusion that these molecules
      participate in the eventual structural stability of synaptic connections, as they
      do in coagulation cascades, and focus trophic activity on surviving terminals
      during periods of selective contact elimination. In disease states, this
      imbalance is likely to be shifted in favor of destabilizing forces: increased
      and/or altered protease activity, enhanced PAR influence, decreased and/or
      altered protease inhibitor function, reduction and/or alteration in tTG
      expression and activity, and alteration in its substrate profile. This imbalance
      further initiates a cascade of events leading to inappropriate programmed cell
      death and may well be considered evidence of synaptic apoptosis.

PMID- 11597004
TI  - Adipokinetic hormones of insect: release, signal transduction, and responses.
AB  - Flight activity of insects provides an attractive yet relatively simple model
      system for regulation of processes involved in energy metabolism. This is
      particularly highlighted during long-distance flight, for which the locust
      constitutes a well-accepted model insect. Peptide adipokinetic hormones (AKHs)
      are synthesized and stored by neurosecretory cells of the corpus cardiacum, a
      neuroendocrine gland connected with the insect brain. The actions of these
      hormones on their fat body target cells trigger a number of coordinated signal
      transduction processes which culminate in the mobilization of both carbohydrate
      (trehalose) and lipid (diacylglycerol). These substrates fulfill differential
      roles in energy metabolism of the contracting flight muscles. The molecular
      mechanism of diacylglycerol transport in insect blood involving a reversible
      conversion of lipoproteins (lipophorins) has revealed a novel concept for lipid
      transport in the circulatory system. In an integrative approach, recent advances
      are reviewed on the consecutive topics of biosynthesis, storage, and release of
      insect AKHs, AKH signal transduction mechanisms and metabolic responses in fat
      body cells, and the dynamics of reversible lipophorin conversions in the insect
      blood.

PMID- 11597005
TI  - Iron metabolism in mammalian cells.
AB  - Most living things require iron to exist. Iron has many functions within cells
      but is rarely found unbound because of its propensity to catalyze the formation
      of toxic free radicals. Thus the regulation of iron requirements by cells and the
      acquisition and uptake of iron into tissues in multicellular organisms is tightly
      regulated. In humans, understanding iron transport and utility has recently been
      advanced by a "great conjunction" of molecular genetics in simple organisms,
      identifying genes involved in genetic diseases of metal metabolism and by the
      application of traditional cell physiology approaches. We are now able to
      approach a rudimentary understanding of the "iron cycle" within mammals. In the
      future, this information will be applied toward modulating the outcome of
      therapies designed to overcome diseases involving metals.

PMID- 11597006
TI  - Special cytochemistry in cell biology.
AB  - Cytochemistry is a science of localizing chemical components of cells and
      organelles on histological sections by using various techniques. We first aimed
      at studying cytochemistry by developing new techniques using various principles
      such as enzyme cytochemistry, microincineration, microspectrophotometry,
      radioautography, cryo-techniques, X-ray microanalysis and immunocytochemistry. We
      first concentrated on developing methodologies in the 1960s to 1970s. We then
      applied these special techniques to various kinds of cells in men and animals.
      Earlier, I proposed to classify these methods into three categories, i.e.,
      chemical, physical, and biological techniques. The methodology has been well
      developed to form a new science which should be designated as "general
      cytochemistry" similarly to the general histology. On the other hand, these
      techniques should be applied to various cells in various organ systems, such as
      the skeletal, muscular, digestive, respiratory, urinary, reproductive, endocrine,
      circulatory, nervous and sensory systems similarly to the special histology or
      the histology of organs. I summarize the results of cytochemical studies on cells
      of various organs carried out in our laboratory during these 44 years since 1955.
      The results obtained from cytochemical studies applied to various cells in
      respective organ systems should be designated as "special cytochemistry."

PMID- 11597007
TI  - Expanding indications for lymphatic mapping and sentinel lymph node biopsy in the
      breast cancer population.

PMID- 11597008
TI  - Role for sentinel lymph node dissection in the management of large (> or = 5 cm)
      invasive breast cancer.
AB  - BACKGROUND: Sentinel lymph node dissection (SLND) for small, early-stage breast
      cancer is well accepted. However, the role of SLND for large primary breast
      cancer is controversial. We investigated the feasibility and clinical
      applicability of SLND in patients with large (> or = 5 cm) breast cancers and
      clinically negative axillae. METHODS: A prospectively entered database was used
      to identify all patients who underwent surgical management of histopathologically
      confirmed primary breast carcinomas > or = 5 cm in diameter between September
      1991 and August 2000. Patients who had clinically negative axillae and underwent
      SLND followed by completion axillary lymph node dissection (ALND) were selected
      for the study. The positivity rate, accuracy rate, and false-negative rate of
      SLND were determined. RESULTS: Of the 41 patients selected for the study, 24 had
      infiltrating ductal carcinoma and 17 had infiltrating lobular carcinoma. Mean
      tumor size was 7.12 cm (range, 5-23 cm). At least one sentinel lymph node (SLN)
      was identified in all cases. Thirty patients had tumor-positive SLNs. Axillary
      metastasis was also identified in one patient who did not have a positive SLN.
      Thus, SLN status accurately predicted regional nodal status in 98% (40 of 41) of
      cases. The false-negative rate of SLND was 3% (1 of 31). None of the three
      patients with SLN micrometastasis, defined as a tumor focus < or = 2 mm, had
      tumor deposits in nonsentinel axillary lymph nodes. Only SLN macrometastasis (> 2
      mm tumor deposit) and primary tumor size > or = 7 cm predicted nonsentinel
      axillary metastasis with significance on multivariate analysis (P = .008 and P =
      .046, respectively). CONCLUSIONS: SLND is feasible and accurate in patients with
      large breast cancers and clinically negative axillae. Axillary lymph node
      dissection can be avoided in nearly one third of patients by focused examination
      of the SLN.

PMID- 11597009
TI  - A comparison of ink-directed and traditional whole-cavity re-excision for breast
      lumpectomy specimens with positive margins.
AB  - BACKGROUND: Excising a breast tumor with negative margins minimizes local
      recurrence. With a positive margin, the standard re-excision consists of excising
      the whole cavity and all surrounding breast tissue. By marking the sides of the
      lumpectomy specimen with six different colored inks, the surgeon can limit the re
      excision to the involved margin. We compared the local recurrence rate after
      these two re-excision methods. METHODS: Records were reviewed of 527 women (546
      breasts) treated with lumpectomy at two institutions. The log-rank test was used
      to compare the local recurrence-free survival. RESULTS: Of 546 tumors, 245 (45%)
      had negative margins on the initial lumpectomy and were not re-excised. Fifty
      five percent had a positive or close margin; 181 underwent whole-cavity re
      excision, and 120 had ink-directed re-excision. The mean follow-up time was 3.4
      years. There was no significant difference in local recurrence for the patients
      whose initial margin was negative (3.7%) compared with the 243 patients with
      initially positive margins who underwent a re-excision (3.3%). Eleven of 181 (6%)
      patients undergoing a whole-cavity re-excision developed a local recurrence,
      compared with none of 120 (0%) patients with an ink-directed re-excision (P = not
      significant). Tissue mass excised was significantly smaller in the ink-directed
      group (23 vs. 83 g, P < .05). CONCLUSIONS: Ink-directed re-excision of lumpectomy
      specimens with positive margins minimizes the amount of breast tissue removed
      without increasing the incidence of local recurrence and is therefore preferable
      to the standard whole-cavity method.

PMID- 11597010
TI  - Palpable breast cancers are inherently different from nonpalpable breast cancers.
AB  - BACKGROUND: We examined the clinicopathologic profile of T1 cancers to determine
      whether palpable cancers are different from nonpalpable cancers. METHODS: A
      prospective database was reviewed. Palpable T1 cancers were compared with
      nonpalpable T1 cancers. Initial significance was determined by chi2 analysis.
      Factors found to be significant were then reanalyzed. controlling for tumor size
      by logistic or linear regression, as appropriate. RESULTS: Of 1263 T1 cancers
      treated between 1981 and 2000, 857 (68%) were palpable and 401 (32%) were
      nonpalpable. Palpability correlated with pathologic tumor size, mitotic grade,
      nuclear grade, high S-phase, lymphovascular invasion, nodal positivity, and lack
      of extensive intraductal component, multifocality, and multicentricity. There was
      no significant difference in estrogen receptor, progesterone receptor or Her
      2/neu status, ploidy, or DNA index. Breast cancer-specific survival was worse for
      patients with palpable cancers. CONCLUSIONS: Palpable cancers are inherently
      different from nonpalpable cancers, with a less diffuse growth pattern, higher
      metastatic potential, higher proliferative activity, more nuclear abnormalities,
      and a worse prognosis.

PMID- 11597011
TI  - Randomized prospective evaluation of a novel technique for biopsy or lumpectomy
      of nonpalpable breast lesions: radioactive seed versus wire localization.
AB  - BACKGROUND: Standard wire localization (WL) and excision of nonpalpable breast
      lesions has several shortcomings. METHODS: Ninety-seven women with nonpalpable
      breast lesions were prospectively randomized to radioactive seed localization
      (RSL) or WL. For RSL, a titanium seed containing 125I was placed at the site of
      the lesion by using radiographical guidance. The surgeon used a handheld gamma
      detector to locate and excise the seed and lesion. RESULTS: Both techniques
      resulted in 100% retrieval of the lesions. Fewer RSL patients required resection
      of additional margins than WL patients (26% vs. 57%, respectively, P = .02).
      There were no significant differences in mean times for operative excision (5.4
      vs. 6.1 minutes) or radiographical localization (13.9 vs. 13.2 minutes). There
      were also no significant differences in the subjective ease of the procedures as
      rated by surgeons, radiologists, and patients. All WLs were carried out on the
      same day as the excision, whereas RSL was performed up to 5 days before the
      operative procedure. CONCLUSIONS: RSL is as effective as WL for the excision of
      nonpalpable breast lesions and reduces the incidence of pathologically involved
      margins of excision. RSL also reduces scheduling conflicts and may allow
      elimination of intraoperative specimen mammography. RSL is an attractive
      alternative to WL.

PMID- 11597012
TI  - Sentinel node biopsy for cutaneous melanoma in the head and neck.
AB  - BACKGROUND: Selective sentinel lymphadenectomy has gained widespread acceptance
      for staging of melanomas arising in the trunk and extremities, but the complex
      lymphatic drainage of the head and neck area has limited its application in this
      area. METHODS: We performed a retrospective analysis of patients who underwent
      selective sentinel lymphadenectomy for cutaneous melanoma of the head and neck at
      the University of Alabama at Birmingham from 1997 through 2000, by using a
      standard technique of preoperative lymphoscintigram and biopsy guided with blue
      dye injection and a handheld gamma probe. Complete lymph node dissection was
      recommended only for tumor-positive sentinel lymph nodes (SLNs). Survival curves
      were constructed with the Kaplan-Meier method. Fisher's exact test was used for
      comparisons. Significance was defined as P < .05. RESULTS: Thirty-eight patients
      underwent selective sentinel lymphadenectomy with the standard technique during
      the study period. A majority (82%) of patients were men with a median age of 55
      years. The most common site of the primary tumor was the face (44%), followed by
      the scalp (24%). Mean tumor thickness was 2.5 mm. The sentinel node was
      identified during surgery in 35 patients (92%). Before the use of the handheld
      gamma probe, the identification rate of the SLN was only 56%. A single SLN was
      identified in 53% of cases. The incidence of metastases in SLN was 11.4%. With a
      mean follow-up of 17 months, the actuarial 3-year overall survival was 92%. The
      accuracy of the selective sentinel lymphadenectomy in this series was 80%.
      CONCLUSIONS: Selective sentinel lymphadenectomy in the head and neck region is a
      technically demanding procedure, but the combined use of blue dye and gamma-probe
      radiolocalization can be a reliable method of staging regional lymph nodes and
      determining the need for elective lymphadenectomy.

PMID- 11597013
TI  - Prospective evaluation of office-based parotid ultrasound.
AB  - BACKGROUND: Differentiation of parotid neoplasms from extraparotid upper cervical
      lesions is difficult by physical examination. The purpose of this report is to
      identify the role of office-based parotid ultrasound (US) in the evaluation of
      periauricular masses. METHODS: A prospective database including the results of
      physical examination, office-based US, and the corresponding pathology was
      reviewed. Soft-tissue US was performed with a 7.5-mHz parallel probe with
      biplanar imaging. RESULTS: Thirty-eight patients were evaluated over a 28-month
      period (mean age. 45 years; range, 23-78 years). US demonstrated a mass within
      the substance of the parotid (n = 23, 61%), outside the parotid (n = 11, 29%), or
      diffuse parotitis (n = 4, 10%). Intraparotid masses were preauricular (n = 14),
      postauricular (n = 5), or upper cervical (n = 4) and were solid (n = 22) or
      cystic (n = 1). Patients with solid intraparotid masses underwent superficial (n
      = 20) or total parotidectomy (n = 2). Benign (n = 19) and malignant (n = 3) solid
      parotid nodules had similar US features of hypoechogenicity with posterior
      enhancement. Indistinct margins were noted in 3 of 3 malignant lesions as well as
      15 of 19 benign nodules (P = .9). Extraparotid masses were confirmed to be nodal
      disease on the basis of observation with resolution (n = 3), fine-needle
      aspiration (n = 6), or surgical removal (n = 2) (mean follow-up, 6 months).
      CONCLUSIONS: Surgical office-based parotid US can delineate the location of
      periauricular mass lesions relative to the parotid gland. Benign and malignant
      lesions have a similar sonographic appearance.

PMID- 11597014
TI  - Frequency and determinants of lymphadenectomy in endometrial carcinoma: a
      population-based study from northern Italy.
AB  - BACKGROUND: The diffusion of pelvic and para-aortic lymphadenectomy for the
      surgical pathological staging of endometrial carcinoma into clinical practice has
      been evaluated only with questionnaire surveys of gynecological oncologists. No
      population-based information is available. METHODS: In this study of operable
      endometrial carcinoma cases registered by the population-based Romagna Cancer
      Registry (northern Italy) between 1987 and 1994, the association of demographic
      (age, time period, place of birth, place of residence, place of treatment, and
      marital status) and pathological factors (histological type, tumor grade,
      myoinvasion, and extension of disease to cervix, serosa, adnexa, and vagina) with
      the probability of lymphadenectomy was evaluated by multiple logistic regression
      analysis. RESULTS: Of the 300 potentially eligible cases, sufficient information
      was obtained for 276 (92%; median age, 63 years; range, 33-87 years). No case of
      para-aortic lymphadenectomy was observed. Pelvic lymphadenectomy was performed in
      86 (31%) cases. The probability of pelvic lymphadenectomy was related to tumor
      grade (positive association), place of treatment, and marital status. All other
      variables, including myoinvasion and extension of disease to the cervix and
      beyond the uterus, had no effect whatsoever. CONCLUSIONS: The most likely
      interpretations of results include poor acceptance of current surgical
      pathological staging criteria and insufficient use of standard diagnostic
      techniques for preoperative and intraoperative assessment of myoinvasion and
      extrauterine spread.

PMID- 11597015
TI  - Comparative expression of the mitotic regulators SAK and PLK in colorectal
      cancer.
AB  - BACKGROUND: Disruption of normal mechanisms for cell cycle regulation is
      important in carcinogenesis. SAK and PLK are members of the polo family of serine
      threonine kinases, which in lower organisms have been shown to be required for
      the precise regulation of mitosis. Studies of human polo family members have
      focused on PLK, which has been found to be overexpressed in several tumor types,
      with the degree of overexpression correlating with adverse clinical outcome.
      However, PLK expression had not previously been analyzed in colorectal cancer.
      SAK, a polo family member with unique properties, had not been systematically
      studied in any tumor type. METHODS: In this study, SAK expression was evaluated
      in a series of sporadic human colorectal cancer specimens (n = 74) and compared
      with that of PLK. Expression was assessed by reverse transcription-polymerase
      chain reaction. RESULTS: In the majority of cases, both SAK and PLK were more
      highly expressed in tumor tissue than in adjacent normal intestinal mucosa.
      Levels of SAK and PLK expression in tumor relative to paired normal mucosa
      correlated directly with patient age and with each other but did not correlate
      with tumor stage. These results suggest a mechanism for augmented disruption of
      mitotic regulation in older patients. CONCLUSIONS: The polo family mitotic
      regulators SAK and PLK are both aberrantly expressed in colorectal cancer. The
      potential prognostic significance of SAK and PLK expression in colorectal cancer
      will be evaluated in the future.

PMID- 11597017
TI  - Does chewing explain the caries-preventive results with xylitol?

PMID- 11597016
TI  - A prospective analysis of plasma endostatin levels in colorectal cancer patients
      with liver metastases.
AB  - BACKGROUND: Circulating inhibitors of angiogenesis have been suggested to affect
      the growth of distant micrometastatic disease in patients with cancer. This study
      was designed to evaluate circulating endostatin levels in colorectal cancer
      patients with liver metastases. METHODS: Plasma samples from 30 colorectal cancer
      patients with liver metastases were analyzed for endostatin and vascular
      endothelial growth factor (VEGF) by using competitive enzyme immunoassays.
      Samples were compared with plasma from age- and sex-matched healthy controls;
      values >2 SD above the control mean were considered elevated. RESULTS: Plasma
      endostatin levels were significantly higher in the 30 cancer patients than
      controls (P < .0001) and correlated with preoperative VEGF levels (P = .0008).
      Eighteen patients underwent surgical treatment (liver resection, n = 10; or
      isolated hepatic perfusion with melphalan, n = 8). Seventeen treated patients
      were available for follow-up. Eight of 11 patients who progressed had elevated
      plasma endostatin levels at the time of progression. None of six patients who
      remained progression free had elevated endostatin levels at last follow-up (P =
      .02). CONCLUSIONS: Plasma endostatin levels are elevated in colorectal cancer
      patients with liver metastases and correlate with VEGF levels. Elevated
      endostatin levels during follow-up are associated with disease progression.
      Understanding the role of endogenous endostatin in cancer patients may lead to
      novel strategies to inhibit tumor angiogenesis.

PMID- 11597018
TI  - Oral transmission of HIV, a rarity: emerging hypotheses.

PMID- 11597019
TI  - Meta-analytical review of factors involved in dentin adherence.
AB  - Literature data on adherence tests of dentin-bonding systems (DBS) may differ
      widely, even for the same DBS. The problem of bond testing is that materials are
      seldom compared with a standard, and experimental conditions often vary. We
      sought to identify the parameters that influence this variability. Using
      inclusion and exclusion criteria, we conducted a meta-analytical review of 75
      articles, published between 1992 and 1996 in SCI reviews, that give bond strength
      data for 15 dentin-bonding agents of the so-called third and fourth generations.
      Seventeen selected parameters were classified into four groups: Group A includes
      factors related to the dentin substrate (i.e., nature of teeth); group B,
      composite and bonding area (i.e., composite stiffness); group C, storage
      conditions of the bonded samples (i.e., thermocycling); and group D, test design
      (i.e., crosshead speed). For each report, the experimental features, the bond
      strength means and standard deviations, and the failure mode were extracted and
      tabulated. Statistical Analysis System software was used to perform Pearson
      correlation analysis and analysis of variance, with bond strength as the
      dependent variable and experimental conditions as the independent variables. The
      meta-analytical review highlighted the significant influence of various
      parameters in the different groups: origin of dentin, types of teeth, pulpal
      pressure, tooth storage temperature, maximum storage time of teeth, and dentin
      depth in group A; type and stiffness of composite and bonding area in group B;
      storage of bonded samples (medium, temperature, and time) in group C, and testing
      mode and crosshead speed in group D. A significant positive correlation was
      observed between the mean bond strength and the rate of cohesive failure. It can
      be concluded from this study that some of these parameters should be controlled
      by the use of a standardized protocol. Unfortunately, the substrate-related
      variables are more difficult to control, even though their influence is
      consistent.

PMID- 11597020
TI  - The induction of micronuclei in vitro by unpolymerized resin monomers.
AB  - Components of resin materials may damage DNA, leading to genetic alterations in
      mammalian cells. Here, monomers were analyzed for the induction of chromosomal
      aberrations indicated by micronuclei induced in V79 cells. A dose-related
      increase in the numbers of micronuclei was observed with triethyleneglycol
      dimethacrylate (TEGDMA), 2-hydroxyethyl methacrylate (HEMA), and glycidyl
      methacrylate (GMA). These effects were reduced, however, by a metabolically
      active microsomal fraction from rat liver. The very low activity of Bis-GMA and
      UDMA and the elevated numbers of micronuclei caused by high concentrations of
      methyl methacrylate and bisphenol A were associated with cytotoxicity. Our
      findings provide evidence for the induction of micronuclei by TEGDMA, HEMA, and
      GMA under physiological conditions, indicating clastogenic activity of these
      chemicals in vitro. Since it has been shown that TEGDMA also caused gene
      mutations and DNA sequence deletions in mammalian cells, the activity of this
      substance should be analyzed in vivo.

PMID- 11597021
TI  - Tuned aperture computed tomography to evaluate osseous healing.
AB  - Quantification of osseous healing is a challenging task, requiring expensive
      advanced imaging modalities. To improve diagnostic osseous imaging, we undertook
      this prospective study to explore the potential of Tuned Aperture Computed
      Tomography. Eighty defects in 20 rabbit mandibles, randomly carrying an
      osteoblast suspension or a polymer matrix or a combination thereof or no
      treatment, were imaged at 3, 6, 9, and 12 weeks post-surgery. TACT slices,
      iteratively restored TACT, and conventional digital radiographs were evaluated.
      Mean-gray-value distribution within regions of interest was correlated with
      histomorphometric data. Lesions treated with osteoblast/polymer-matrix delivery
      systems demonstrated the highest mean gray-value, while the diagnostic efficacy
      of TACT-IR was significantly better than that of other imaging modalities (p <
      0.001). Thus, TACT is an accurate imaging modality for non-destructive
      quantification of osseous dynamics.

PMID- 11597023
TI  - Relationship between upper body obesity and periodontitis.
AB  - Upper body obesity, related to visceral fat accumulation, is known to increase
      the risk of various adult diseases, especially type 2 diabetes and cardiovascular
      disease. This study was conducted to clarify the relationship between upper body
      obesity and periodontitis. We studied 643 apparently healthy, dentulous Japanese
      adults who attended programs at Fukuoka Health Promotion Center. Waist-hip ratio,
      body-mass index (BMI), and body fat were significant risk indicators for
      periodontitis after adjustment for known risk factors (p < 0.002). Subjects were
      divided into four BMI (or body fat) categories. In only the subjects with high
      waist-hip ratio, higher categories of BMI (or body fat) significantly increased
      the adjusted risk of periodontitis, compared with subjects with low waist-hip
      ratios and the lowest category of BMI (or body fat). The reported relationship
      between cardiovascular disease and periodontitis should be reconsidered, since
      abdominal adiposity or visceral fat can be related to both diseases.

PMID- 11597022
TI  - Oral function and diet quality in a community-based sample.
AB  - Overall diet quality indices, such as the Healthy Eating Index (HEI), are
      preferred for epidemiological studies, yet studies in dentistry have focused on
      isolated dietary components. This study investigated the influence of socio
      demographic and masticatory variables (masticatory performance, bite force,
      number of posterior functional tooth units, TMJ disorder, and dentition status)
      on overall diet quality in a community-based sample (n = 731). Cross-sectional
      data were derived from clinical examinations, bite force recordings, masticatory
      performance measurements, and two 24-hour dietary recalls. Females, European
      Americans, and older subjects had better HEI scores than males, Mexican
      Americans, and younger subjects, respectively. Income, education, and the
      masticatory variables were not related to diet quality. Analyses according to
      dentition status (good dentition, compromised dentition, partial denture, and
      complete dentures) showed no inter-group differences for HEI except for the age
      groups. The results suggest that the chewing-related factors evaluated in this
      sample are not predictors of overall diet quality across the socio-demographic
      groups.

PMID- 11597024
TI  - Decrease of sulfate-reducing bacteria after initial periodontal treatment.
AB  - Sulfate-reducing bacteria (SRB) are associated with periodontitis, but it is
      unknown if elimination of these potential pathogens accompanies clinical
      improvement. This longitudinal study examined the occurrence of SRB and clinical
      effects following scaling and root planing. In this study, the presence of
      periodontal SRB was determined in 38 selected patients before and six months
      after mechanical therapy. SRB were detected by the enrichment culture technique.
      Mechanical periodontal treatment resulted in elimination of SRB in 89% of the
      patients, and 95% of the sites (n = 76). SRB were significantly reduced in
      patients with progressive, adult, and refractory periodontitis. The elimination
      of SRB was accompanied by clinical improvement. The mean gain of attachment of
      these pockets was 3 mm (p < 0.001). The reductions in pocket depth (p < 0.001)
      and bleeding were significant (p < 0.001). Persistence of SRB correlated with the
      initial pocket depth (p < 0.02) and attachment level (p < 0.02), and with
      bleeding of the site after treatment (p < 0.05). In conclusion, mechanical
      debridement is generally effective for the elimination of SRB.

PMID- 11597025
TI  - Elevated systemic concentrations of soluble ICAM-1 (sICAM) are not reflected in
      the gingival crevicular fluid of smokers with periodontitis.
AB  - Raised serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) in
      smokers could have immunomodulatory effects in periodontitis. The aim of this
      study was to compare serum and gingival crevicular fluid (GCF) concentrations of
      sICAM-1 in smokers and non-smokers with periodontal disease. sICAM-1 in serum and
      GCF collected from age- and gender-matched smokers (n = 14) and non-smokers (n =
      14) with periodontitis were measured by ELISA. Mean serum sICAM-1 concentrations
      were significantly elevated in smokers (331 ng mL(-1)), compared with non-smokers
      (238 ng mL(-1), p = 0.008). However, the concentration of sICAM-1 in the GCF was
      significantly lower in the smokers (83 ng mL(-1)), compared with non-smokers (212
      ng mL(-1), p = 0.013). The difference between concentrations of sICAM-1 in GCF
      and serum was significant only in smokers (p < 0.001). Since GCF is a serum
      derived tissue exudate, these results suggest that, in smokers, circulating sICAM
      1 molecules are affected either in their passage from the periodontal
      microvasculature or within the periodontal tissues.

PMID- 11597026
TI  - Relationship between tooth loss and electrocardiographic abnormalities in
      octogenarians.
AB  - Recent reports have suggested that periodontal disease is a risk factor for
      coronary heart disease (CHD). However, little is known about the relationship
      between periodontal disease and CHD in the very elderly. Therefore, we evaluated
      the association between tooth loss and abnormal ECG findings in octogenarians. Of
      the 1,282 octogenarians in Fukuoka Prefecture, Japan, 697 participated. Oral
      examinations--including a tooth count and an assessment of the Community
      Periodontal Index--and a 12-lead ECG were performed. Logistic regression analysis
      revealed that individuals with < 20 teeth had increased prevalence of ST segment
      depression, and T-wave abnormalities, after we adjusted for gender, smoking,
      serum cholesterol and glucose, blood pressure, and body mass index. Compared with
      individuals with > or = 20 teeth, edentulous individuals had an increased
      prevalence of T-wave abnormalities and arrhythmias after adjustment for coronary
      risk factors. We conclude that tooth loss may be an independent predictor of
      abnormal ECG findings in octogenarians.

PMID- 11597027
TI  - Transforming growth factor-beta1 and basic fibroblast growth factor modulate
      osteocalcin and osteonectin/SPARC syntheses in vitamin-D-activated pulp cells.
AB  - Vitamin D deficiency elicits hypocalcified dentin. However, little is known about
      the action of vitamin D on the syntheses of dentin matrix proteins. In this
      study, we examined the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the
      expressions of osteocalcin and osteonectin/secreted protein, acidic and rich in
      cysteine (SPARC), by human pulp cells in the presence or absence of transforming
      growth factor-beta1 (TGF-beta1) or basic fibroblast growth factor (bFGF).
      1,25(OH)2D3 markedly increased osteocalcin at protein and mRNA levels. The
      osteocalcin level induced by 1,25(OH)2D3 was decreased and increased by TGF-beta1
      and bFGF, respectively. 1,25(OH)2D3 suppressed SPARC synthesis at protein and
      mRNA levels. TGF-beta1, but not bFGF, increased SPARC synthesis in the presence
      of 1,25(OH)2D3. SPARC, but not osteocalcin, increased DNA synthesis in pulp
      cells. These findings suggest that 1,25(OH)2D3 and growth factors interactively
      regulate the expression of osteocalcin and SPARC in pulp cells, and that SPARC
      can stimulate DNA synthesis by pulp cells.

PMID- 11597028
TI  - Gelatinase A (MMP-2) in developing tooth tissues and amelogenin hydrolysis.
AB  - Matrix metalloproteinases (MMPs) are thought to play important roles during
      enamel and dentin biomineralization. Previously, membrane type-1 matrix
      metalloproteinase (MT1-MMP) was localized to the plasma membranes of ameloblasts
      and odontoblasts of the developing tooth. The best-characterized function of MT1
      MMP is to initiate the activation of gelatinase A (MMP-2). Thus, we hypothesized
      that gelatinase A may also be expressed by developing tooth tissues. A full
      length porcine gelatinase A mRNA was isolated by RT-PCR homology cloning of an
      enamel-organ-specific cDNA library. Northern blot and in situ hybridization
      analyses demonstrated gelatinase A expression in developing tooth tissues.
      Immunohistochemical analysis localized gelatinase A close to the plasma membrane
      of these tissues. Furthermore, recombinant gelatinase A was demonstrated to
      cleave recombinant amelogenin into several fragments of differing molecular
      masses. Thus, gelatinase A is expressed by developing tooth tissues along with
      its activator MT1-MMP and may, therefore, play an important role during tooth
      development.

PMID- 11597029
TI  - Expression of bone matrix protein mRNAs by primary and cloned cultures of the
      regenerative phenotype of human periodontal fibroblasts.
AB  - The successful regeneration of periodontal tissues is dependent, in part, on the
      ability of cells to reconstitute the mineralized tissues of cementum and bone.
      The aim of the present study was to characterize regeneration-associated cells in
      terms of their ability to express mineralized tissue macromolecules. Following
      guided tissue regeneration, cell cultures were established from regenerating
      tissue, periodontal ligament, and gingiva. Additionally, these cells were
      transfected, and single-cell-derived clones were established. Following treatment
      with platelet-derived growth factor-BB and insulin-derived growth factor-1, the
      presence of mRNA for alkaline phosphatase, osteocalcin, bone sialoprotein,
      osteopontin, and bone morphogenetic proteins-2 and -4 was assessed. The three
      cell types expressed similar mRNA levels for alkaline phosphatase, bone
      morphogenetic protein-2, and bone morphogenetic protein-4, whereas the expression
      of osteopontin, osteocalcin, and bone sialoprotein was greater in the periodontal
      ligament and regenerating tissue fibroblasts compared with the gingival
      fibroblasts. The two growth factors did not affect the expression of any of the
      genes. This study has identified markers that correlate with the known ability of
      periodontal ligament and regenerating tissue-derived fibroblasts to facilitate
      regeneration of the mineralized tissues of the periodontium.

PMID- 11597030
TI  - Contributions of three glycosyltransferases to sucrose-dependent adherence of
      Streptococcus mutans.
AB  - Streptococcus mutans produces 3 types of glucosyltransferase (GTF), whose
      cooperative action is considered to be essential for its cellular adherence to
      the tooth surface. However, the precise mechanisms for synthesizing adhesive
      glucans and the specific roles of each GTF in cellular adherence to smooth
      surfaces have not been elucidated. In the present study, seven types of isogenic
      mutants of S. mutans MT8148 lacking GTFB, GTFC, and/or GTFD activities were
      constructed by inactivation of the genes encoding GTFB, GTFC, and/or GTFD.
      Furthermore, recombinant GTFB, GTFC, and GTFD were prepared from Escherichia coli
      cells harboring recombinant plasmids containing each of the gtf genes. Using
      these GTF-deficient mutants and rGTFs, we reconstituted sucrose-dependent
      adherence of S. mutans resting cells and examined the role of each GTF in vitro.
      The highest level of sucrose-dependent adherence was found at the ratio of 20
      rGTFB:1 rGTFC:4 rGTFD in both the resting cells of GTF-deficient mutants and
      insoluble glucan synthesized by rGTFs. Moreover, when rGTFC and rGTFD were both
      present at concentrations of 1.5 mU and 6 mU, respectively, the insoluble glucan
      synthesized from sucrose by the rGTFs showed a high level of adhesiveness to
      smooth surfaces, even without rGTFB. These results suggest that the presence of
      all three GTFs at the optimum ratio is necessary for sucrose-dependent adherence
      of S. mutans, and that GTFC and GTFD may play significant roles in the synthesis
      of adhesive and insoluble glucan from sucrose.

PMID- 11597031
TI  - The capacity of Porphyromonas gingivalis to multiply under iron-limiting
      conditions correlates with its pathogenicity in an animal model.
AB  - Isolates of Porphyromonas gingivalis have various abilities to induce infections
      in an animal model. The hypothesis of this study was that pathogenic strains of
      P. gingivalis could multiply under iron-limiting conditions, while non-pathogenic
      strains could not. Three pathogenic strains (W50, W83, and ATCC 49417) grew to a
      final optical density (660 nm) > 2 in horse serum, while the growth of the 3 non
      pathogenic strains (ATCC 33277, LB13D-2, and HW24D-1) was negligible. When an
      excess of hemin or ferric chloride was added to the serum, significant growth of
      the non-pathogenic strains occurred. Under iron-limiting conditions, the
      pathogenic strains of P. gingivalis had a much lower requirement for human iron
      loaded transferrin and hemin than the non-pathogenic strains. Proteolytic
      degradation of transferrin, which may be associated with the release of iron, was
      not markedly different for pathogenic and non-pathogenic strains. In addition, no
      relationship could be established between the level of 55Fe uptake from 55Fe
      transferrin and the pathogenicity of strains. Our study provided evidence that
      the ability of P. gingivalis to multiply in vitro under iron-limiting conditions
      may be correlated with its ability to induce infections in an animal model.
      Isolates of P. gingivalis possessing a low requirement for iron are likely to
      have a higher potential for initiating periodontal infections.

PMID- 11597032
TI  - DNA diagnosis in hereditary nephropathies.
AB  - Increasing knowledge regarding the genetic basis of hereditary nephropathies has
      contributed much to the understanding of their pathogenesis. In addition,
      localization and identification of genes have offered new tools for the
      classification and diagnostics of hereditary nephropathies. The diagnosis at the
      DNA level, however, differs from classical diagnostic procedures in many
      respects. The current status of DNA diagnostics in hereditary nephropathies is
      summarized in this review, which includes a discussion of the major principles
      and limitations.

PMID- 11597033
TI  - Steroid and cyclophosphamide therapy for IgA nephropathy associated with
      crescenteric change: an effective treatment.
AB  - BACKGROUND: IgA nephropathy is the most common form of idiopathic
      glomerulonephritis. There is no current consensus on treatment for this
      condition. We report on the effect of immunosuppression with corticosteroids and
      cyclophosphamide for the treatment of IgA nephropathy associated with
      crescenteric change. METHODS: The effect of oral prednisolone (0.8 mg/kg
      initially, reducing to 0.4 mg/kg after 4 weeks) and cyclophosphamide (1.5 mg/kg)
      given until a plateau of response was obtained was studied in 9 patients with IgA
      nephropathy associated with severe inflammatory change and crescents. The initial
      diagnostic renal biopsies of these patients revealed 25-70% of the glomeruli
      effected with active cellular crescents. When response to therapy, plateaued
      cyclophosphamide was discontinued and prednisolone reduced from 0.4 mg/kg. Follow
      up renal biopsy was performed in 8 of the 9 patients. Patients were maintained on
      prednisolone (5- 7.5 mg) and azathioprine (1 mg/kg) for further 2 years. RESULTS:
      The mean time until discontinuation of cyclophosphamide was 17.8 weeks (+/-1.23,
      range 12-25 weeks). There were no serious complications of therapy. There was an
      improvement in renal function in all patients with serum creatinine falling from
      a mean of 149.6+/-16.5, range 81-227 micromol/l to 116.4+/-8.6, range 80-158
      micromol/l, p=0.01. Creatinine clearance improved from a mean of 57.1+/-9.9,
      range 21-104 ml/min to 87.2+/-10.1, range 39-125 ml/min, p=0.004. 24-hour urinary
      total protein fell over the same time m period from a mean of 4.54+/-1.1, range
      1.0-11.27 g to 1.2+/-0.27, range 0.01-2.65 g, p=0.004. There were no significant
      differences in blood pressure during this time. Repeat renal biopsies showed
      significant degrees of histological improvement with healing of crescents and a
      reduction in acute inflammatory change in all except one patient. The mean period
      of follow-up after cessation of cyclophosphamide was 17.4+/-2.8 months, range 10
      36 months. There was no significant change over this period in serum creatinine,
      creatinine clearance or urinary protein losses. CONCLUSION: These data suggest
      that IgA nephropathy associated with severe inflammatory and crescenteric change
      can be effectively and safely treated with a low-cost regime based on oral
      corticosteroids and cyclophosphamide tailored to a plateau of treatment response
      in individual patients.

PMID- 11597035
TI  - Multiple myeloma and light chain-associated nephropathy at end-stage renal
      disease in the United States: patient characteristics and survival.
AB  - AIMS: The patient characteristics and clinical course of nephropathy associated
      with multiple myeloma/light chain disease (MMN) has not been described for a
      national sample of end-stage renal disease patients. METHODS: 375,152 patients in
      the United States Renal Data System were initiated on ESRD therapy between
      January 1, 1992 and June 30, 1997, and were analyzed in a retrospective registry
      study of MMN (PDIS=2030A, 2030B, 2030Z, and 203Z). RESULTS: Of the study
      population, 3298 (0.88%) had MMN. Patients with MMN were disproportionately male
      (59.5% vs. 53.2%) and Caucasian (76.2% vs. 64.1%, p < 0.01 by Chi-square for both
      comparisons) and older (68.00+/-11.78 vs. 60.69+/-16.55 years, p < 0.01 by
      Student's t-test). In logistic regression analysis, patients with MMN were more
      likely male and Caucasian, were older, had lower serum hemoglobin, higher
      creatinine, and more likely to have been started on hemodialysis than peritoneal
      dialysis. The two-year all-cause mortality of patients with MMN during the study
      period was 58% vs. 31% in all other patients (p < 0.01 by log rank test). In Cox
      regression, MMN was independently associated with decreased all-cause patient
      survival (p < 0.01, hazard ratio for mortality=2.52, 95% CI 2.38-2.67).
      CONCLUSIONS: MMN was associated with Caucasian race, male gender, and older age,
      compared with other ESRD patients. Patients with MMN had evidence of poorer
      medical condition on initiation of dialysis compared to other patients. MMN was
      associated with decreased patient survival after initiation of dialysis, although
      better than in some previous reports, and patients with MMN may be initiated on
      dialysis at a lower level of renal function than other patients with ESRD.

PMID- 11597034
TI  - Differential expression of various cytokine and chemokine genes between
      proliferative and non-proliferative glomerulonephritides.
AB  - BACKGROUND: Intraglomerular cellular proliferation is one of the major
      determinants for dividing various glomerulonephritis (GN) into two groups, such
      as proliferative versus non-proliferative. Cytokines and chemokines are involved
      in the pathogenetic pathways and would affect the functional and histologic
      sequelae. We hypothesized that the morphological difference might be based on the
      differential intrarenal expression of various cytokines and chemokines. We
      quantified the intrarenal gene expression of various cytokines and chemokines,
      and correlated it with clinical parameters. METHODS: Total RNA was extracted from
      54 proliferative GN (PGN) core biopsy specimens and 42 non-proliferative GN
      (NPGN) specimens. Using the internal competitors, RT-PCR was instituted to
      quantify mRNAs. RESULTS: The magnitude of the gene expressions of IL-2, IFN
      gamma, and IFN-gamma/IL-10 ratio were significantly higher in PGN than in NPGN.
      RANTES and IL-8 had more abundant gene messages in PGN. It was shown that Th1
      cytokine was upregulated if GN was mediated by immune complexes regardless of
      cellular proliferation. But chemokines had the elevated levels of expression in
      PGN among immune complex-mediated GN. Up-regulation of the IFN-gamma/IL-10 ratio
      and TNF-alpha was associated with poor renal function at the time of biopsy.
      Renal tissues from the patients with a non-nephrotic range of proteinuria showed
      abundant messages for proinflammatory cytokines and chemokines. CONCLUSION: Th1,
      proinflammatory cytokines, and chemokines were more abundant in proliferative GN,
      and correlated with unfavorable clinical parameters. We propose that the clinical
      manifestations and diverse histologic features of human GN are associated with
      differential expressions of specific cytokines and chemokines.

PMID- 11597036
TI  - Cardiac involvement in autosomal-dominant polycystic kidney disease: a
      hypertensive heart disease.
AB  - BACKGROUND: There is little information regarding the occurrence and distribution
      of cardiovascular abnormalities during the course of autosomal-dominant
      polycystic kidney disease (ADPKD). We conducted a cross-sectional study in three
      different groups of ADPKD patients to determine the profile and prevalence of
      cardiac involvement in this population. METHODS: Doppler color echocardiography
      was performed in 130 ADPKD patients. Patients were divided into normotensive
      (Group I, n=60), hypertensive (Group II, n=32) and those undergoing hemodialysis
      (Group III, n=38). RESULTS: There was a progressive increase in left ventricular
      mass (LVM) index (88.6+/-19.7, 127.6+/-40.4 and 150.5+/-56.5 g/m2, p < 0.0001)
      and in the prevalence of left ventricular hypertrophy (LVH) (3%, 43%, 62%, p <
      0.0001) in Groups I, II and III, respectively. E/A ratio < 1 was found in 2% of
      normotensives, 46% of hypertensives and 62% of hemodialysis patients (p <
      0.0001). Prevalence ofmitral valve prolapse and aortic and/or mitral
      regurgitation was 4.3% and 8.6%, respectively, in non-dialysis patients. The
      majority of valvular abnormalities occurred in dialysis patients, and were
      generally related to annular mitral calcification (28%) or aortic valve
      calcification (38%). Age, sex, systolic blood pressure (BP) and hemoglobin were
      independent predictors of LVM index in the entire population, systolic BP and
      creatinine in non-dialysis patients and systolic BP in dialysis patients. Age,
      heart rate and diastolic BP in the entire group, and age, heart rate and LVM
      index in non-dialysis patients remained as independent predictors of abnormal
      diastolic function. CONCLUSIONS: Cardiac involvement in ADPKD patients is a
      continuous process that evolves during the course of this disease. It is
      characterized by a low prevalence of specific valvular abnormalities, a
      progressive increase in LVM, LVH, and diastolic dysfunction, which are greatest
      in the latter stages of the disease. This study confirms the major influence of
      BP on cardiovascular abnormalities of ADPKD patients.

PMID- 11597037
TI  - Are conventional cardiovascular risk factors predictive of two-year mortality in
      hemodialysis patients?
AB  - BACKGROUND: In general population hypertension, diabetes mellitus, overweight,
      hyperlipidemia and smoking are well-established risk factors for cardiovascular
      disease. However, the effect of these conventional risk factors on cardiovascular
      disease and mortality of patients on hemodialysis is not well understood. Indeed,
      some risk factors such as high blood pressure, hyperlipidemia and excess weight
      have been recently claimed to correlate with improved survival. OBJECTIVE: This
      study was undertaken to define the prevalence of these conventional risk factors
      in 453 hemodialysis patients, predominantly African-Americans, to determine their
      influence on two-year survival. RESULT: High cholesterol was found in 30% of the
      patients, high LDL-cholesterol in 25% and high triglycerides in 16%.
      Lipoprotein(a) (LP(a)) was elevated in 68% of the patients. 31% of our patients
      had predialysis mean arterial blood pressure (MAP) over 114, and 25% were obese
      based on a body mass index (BMI) over 30, 26% were diabetic and 25% were active
      smokers. Smoking was more common among our male and Caucasian patients. The
      aggregate score for the risk factors were 2.4+/-0.1 per patient, which increased
      to 3.2+/-0.1 in patients with obesity or diabetes, to 3.0+/-0.1 with hypertension
      and to 2.8+/-0.1 with active smoking. In multivariate Cox model analysis,
      prealbumin, body weight and blood pressure showed a positive correlation with two
      year survival whereas diabetes mellitus had a negative correlation.
      Hyperlipidemia did not correlate to patients' two-year mortality. Smoking was
      associated with higher mortality, but that did not reach statistical
      significance. CONCLUSION: Conventional risk factors at least over a two-year
      period do not readily account for the higher mortality of a group of
      predominantly African-American patients on hemodialysis. The lack of prediction
      is speculated to be partly due to the overriding beneficial effects of better
      nutrition and due to the presence of other yet to be well-defined factors such as
      hyperhomocysteinemia, oxidative stress, coronary calcification, hitherto
      unidentified uremic toxins or a combination of these factors.

PMID- 11597038
TI  - Factors associated with acceptance of patients for chronic dialysis.
AB  - BACKGROUND/AIMS: There is evidence suggesting that a number of patients with
      chronic renal failure (CRF) are not accepted for maintenance dialysis treatment,
      however, the factors that influence this process are not well known. METHODS:
      Data from patients who died of CRF in the city of Sao Paulo in 1998 were recorded
      from death certificates. The International Classification of Diseases, tenth
      revision, was used to select patients with an underlying cause of death
      associated with CRF. Patients who received dialysis were identified through the
      files of the Sao Paulo State Health Secretariat. Subjects accepted for dialysis
      or not were compared regarding demographic, socioeconomic factors and primary
      renal disease. RESULTS: Of 1225 subjects, 414 (33.8%) received dialysis and 811
      (66.2%) did not. The adjusted odds ratio (OR) (95% CI) of not being accepted for
      dialysis was greater in older (> 65 years; OR: 2.94 (2.28 3.79)) and in younger
      subjects (<18 years; OR: 3.20 (1.16-8.28)) compared to those aged 18-64 years.
      Single subjects had a greater chance of not being accepted for dialysis than
      married individuals (OR: 1.28 (1.01-1.65)). Patients with diabetes were less
      likely to receive dialysis than those with an unknown cause of renal failure (OR:
      1.37 (1.01-1.86)). CONCLUSION: Age, underlying cause of renal failure and social
      support are associated with the acceptance of CRF patients for dialysis. Further
      studies are necessary to examine interventions to improve the access to treatment
      for potentially eligible patients.

PMID- 11597039
TI  - High resistive index of the radial artery is related to early primary
      radiocephalic hemodialysis fistula failure.
AB  - Forty-nine patients who had received radiocephalic hemodialysis fistula
      construction were evaluated with duplex Doppler ultrasonography to characterize
      the Doppler indices of the feed radial arteries just proximal to the site of
      anastomosis. Forty-four patients had fistulas with good function, and 5 patients
      had fistulas with inadequate blood flow or thrombosis within 4 weeks after the
      operation. A preliminary study showed extensive variability in peak systolic
      velocity and end-diastolic velocity in the feed arteries. The resistive index
      dropped significantly 1 week after the operation and remained relatively constant
      over the following 5 weeks. In the success group, the mean resistive index
      measured 1 week after operation was 0.40+/-0.06. It was higher than that of the
      failure group (mean resistive index: 0.52+/-0.06). Among patients with well
      functioning fistulas, diabetic patients had higher resistive indices than did non
      diabetic patients (0.44+/-0.04 vs. 0.37+/-0.06). Our results suggest that a
      higher resistive index of the feed artery is closely related to early autogenous
      primary hemodialysis fistula failure.

PMID- 11597040
TI  - Tsukamurella peritonitis associated with continuous ambulatory peritoneal
      dialysis.
AB  - A case of Tsukamurella peritonitis associated with peritoneal dialysis in a 23
      year-old woman is described. The organism was difficult to identify and was
      mistaken for Corynebacterium and atypical mycobacteria. Despite prolonged,
      multidrug, antimicrobial therapy with conventional antibiotics including
      vancomycin, ciprofloxacin, rifampin, gentamicin and ceftazidime, catheter removal
      was required to successfully treat peritonitis. Human infection due to this
      organism is rare and has been previously reported in only 13 cases, 1 of which
      was peritonitis. We describe here the second case of Tsukamurella peritonitis
      associated with peritoneal dialysis.

PMID- 11597041
TI  - Nephrotic syndrome due to loiasis following a tropical adventure holiday: a case
      report and review of the literature.

PMID- 11597042
TI  - IgA nephropathy and tubular proteinuria in a patient with congenital solitary
      kidney.

PMID- 11597043
TI  - Risk of exposure to hepatitis B and C viruses in hemodialysis patients: a 10-year
      survey.

PMID- 11597044
TI  - RPA position on development of effective collaborative practice models for
      chronic renal care. Renal Physicians Association.

PMID- 11597045
TI  - Associations between the Holden Psychological Screening Inventory and the
      Personality Assessment Screener in a nonclinical sample.
AB  - Associations between two screening inventories of psychopathology were
      investigated using a sample of 156 first-year undergraduates. Analyses supported
      the reliability and validity of all Holden Psychological Screening Inventory
      scales, but only of some of the Personality Assessment Screener scales.
      Orthogonal dimensions of Depression, General Distress, and Antisocial Tendencies
      represented the common latent structure of the two inventories.

PMID- 11597046
TI  - Outcomes for psychiatric patients following first admission: relationships with
      voluntary and involuntary treatment and ethnicity.
AB  - Research suggests that there are ethnic differences in hospitalization outcomes
      for severely mentally ill patients. This study examined ethnic and sex
      differences in admission status, rapid readmission, and discharge placement of
      487 patients on their first psychiatric admission. There were sex differences in
      admission status with significantly more male patients being involuntarily
      admitted than female patients. Ethnic differences in placement at discharge were
      not supported, but involuntarily admitted patients were over-represented in the
      less desirable outcome categories.

PMID- 11597047
TI  - Team members' and supervisors' ratings of team performance: a case of
      inconsistency.
AB  - This study used measures of team performance, organizational support, and
      supervisors' judgment to examine the consistency of ratings of teams by both
      their members as well as their supervisors. For 75 team members from 13 different
      work teams in different organizations Pearson correlation coefficients were used
      to assess the consistency of ratings of these measures within the teams and
      between teams and supervisors. The results indicate the need for rater training,
      both at the team and supervisor levels.

PMID- 11597048
TI  - Mental health variables and positive health practices in early adolescents.
AB  - A sample of 127 adolescents aged 12 to 14 years and attending a middle school
      responded to the Personal Lifestyle Questionnaire, the Depression-Dejection
      subscale of the Profile of Mood States, the Spielberger Trait-Anger Scale, and
      the Revised UCLA Loneliness Scale in classrooms. Using canonical variate
      analysis, three canonical variates emerged in the statistical analysis of the set
      of mental health variables and the set of positive health practice variables, two
      of which had statistically significant canonical correlations. The findings are
      consistent with theory and previous research linking positive health practices to
      depression, anger, and loneliness.

PMID- 11597049
TI  - Effect of response effort on the reward value of distinctively flavored food
      pellets.
AB  - This study was designed to test whether distinctively flavored food pellets, used
      as rewards for lever-pressing by rats, would acquire different reward values as a
      function of the differential effort involved in making the lever pressing
      response which would be predictable from the concept of cognitive dissonance.
      Subjects were seven Long-Evans strain hooded rats, 301-308 days old at the start
      of the study and had had their body weights reduced to 80%, of their free-feeding
      weights. Testing was done in a Y-maze, with food pellets associated with the
      difficult lever-press response serving as the reward for one choice and pellets
      associated with the easy lever-press response for the other. Analysis showed
      there was no preference in the choice of either the "easy" or the "difficult"
      pellets, the choice not being significantly different from chance. This indicated
      that the effort involved in making a response did not affect the reward strength
      of food pellets when used to reward a response with a different topography.

PMID- 11597050
TI  - Sensorimotor gating and attitudes related to schizotypal proneness.
AB  - The magnitude of the startle eyeblink response is diminished when the startle
      eliciting probe is shortly preceded by another stimulus. This so called prepulse
      inhibition is interpreted as an automatic sensorimotor gating mechanism. There is
      substantial support for prepulse inhibition deficits in subjects suffering from
      schizophrenia spectrum disorders and in psychosis-prone normals as well. Thus,
      prepulse inhibition deficits may reflect vulnerability on the hypothesized
      psychopathological continuum from "normal" to "schizophrenia." The present
      experiment investigated the amount of prepulse inhibition in a sample selected
      for "belief in extraordinary phenomena," an attitude related to measures of
      psychosis-proneness. Believers and skeptics were tested in an acoustic prepulse
      inhibition paradigm. As expected presentation of prepulses clearly diminished
      magnitude of startle response, with greatest inhibition effects gained by lead
      intervals of 60 and 120 msec. Patterns of response were identical for believers
      and skeptics, i.e., attitude towards extraordinary phenomena did not seem to be
      related to functional information-processing deficits as has been observed in
      psychosis-prone normals.

PMID- 11597051
TI  - Effect of a perfume on prosocial behavior of pedestrians.
AB  - Several studies have shown that perfumes encourage prosocial behavior of people
      from whom help is requested in the street. Implicit requests for help were
      studied. On a pedestrian walk, a woman confederate, with or without a heavy
      perfume, walked by the subject while dropping a packet of paper handkerchiefs or
      a glove apparently without noticing. Results show that the confederate was warned
      more often when wearing a perfume.

PMID- 11597052
TI  - Outcomes of a leadership intervention for a metropolitan fire department.
AB  - Poor leadership can contribute to job dissatisfaction and employees' "burnout."
      Perceived lack of leadership skills is also a source of stress for supervisors.
      This study evaluated the efficacy of a brief multicomponent leadership
      intervention provided for fire service supervisors in an urban fire department.
      Ratings by 51 line firefighters and 8 first-line supervisors documented
      improvements in their immediate supervisors' performance at 3 mo.
      postintervention. Self-reports by line firefighters also showed improvements in
      perceptions of their ability to attain career goals, which were sustained at 9
      mo. postintervention. There were also improvements on certain stress related
      symptoms indices reported by the sample of firefighter supervisors at both the 3
      mo. and 9-mo. follow-ups. No significant changes on any of these measures,
      obtained at comparable time points, were observed in a (nonequivalent) control
      sample of firefighters and their first-line supervisors in an "untreated" urban
      fire department.

PMID- 11597053
TI  - Three programs for computing Dunn-Sidak critical values.
AB  - The Dunn-Sidak multiple comparison procedure is used to test hypotheses and
      construct confidence intervals for two or more a priori nonorthogonal contrasts
      for population means. The procedure uses a levels that are not available in
      conventional t tables. In 1977 Games prepared a table of two tailed critical
      values that simplifies using the procedure. Researchers are accustomed to
      doubling alpha in a two-tailed t table to obtain the critical value in one tail.
      Unfortunately, doubling alpha in Games's table always gives one tailed critical
      values that are too small. Computational routines using the t inverse function in
      Microsoft Excel 98, SAS, and SPSS are presented for obtaining Dunn-Sidak one- and
      two-tailed critical values for ant familywise error rate, number of contrasts,
      and error degrees of freedom.

PMID- 11597054
TI  - Development of three new scales for assessing clients' perspectives on premarital
      counseling.
AB  - Within a subsample of 73 men and 179 women from a larger study of current and
      former members of the Christian Church (Disciples of Christ), three new scales
      were developed to assess the value attributed to premarital counseling, quality
      of premarital counseling received, and a pastor's competence at premarital
      counseling. Although internal consistency reliability as measured by Cronbach
      alpha was marginally acceptable (.61) for the latter three-item scale, it was
      adequate for the three-item value (.84) and the seven-item quality (.87) scales.
      Evidence for construct validity was limited with respect to demographic variables
      for social class, sex, and religiosity. Those who attended church more frequently
      and women reported lower quality of premarital counseling.

PMID- 11597055
TI  - Mean Beck Depression Inventory-II scores by severity of major depressive episode.
AB  - The Beck Depression Inventory-II total scores of 35 (14%) outpatients who were
      diagnosed with a mild DSM-IV Major Depressive Episode (MDE), 144 (55%)
      outpatients with a moderate MDE, and 81 (31%) outpatients with a severe MDE were
      compared. The mean BDI-II total scores were, respectively, 18 (SD = 8, 99% CI 12
      23), 27 (SD = 10, 99% CI 24-29), and 34 (SD = 10, 99% CI 30-37) (F2.257 = 33.25,
      p<.001). The mean BDI-II total score of the outpatients with a severe specifier
      was significantly higher than the mean BDI-II total score of the outpatients with
      a moderate specifier which was, in turn, significantly higher than the mean BDI
      II total score of the outpatients with a mild specifier.

PMID- 11597056
TI  - Multilevel performance probability: a meta-analytic integration of expectancy and
      self-efficacy.
AB  - A meta-analysis of one approach to measuring expectancy and self-efficacy was
      conducted. Although used for over 25 years, this measure has yet to be named or
      integrated across the two theoretical domains. We proposed to label this measure
      a Multilevel Performance Probability and conducted a meta-analysis. The search
      for empirical tests of expectancy and self-efficacy using this procedure yielded
      16 studies with ratings which could be subjected to meta-analysis. Five studies
      with 8 tests were taken from expectancy studies and 11 studies with 47 tests from
      studies of self-efficacy. In total, the analyses involved 7,444 subjects across
      55 tests of the Multilevel Performance Probability to performance relationship.
      Examination of the measure as a predictor of performance gave a mean r of .51
      (p<.001) which is in the same direction and larger than values from other meta
      analyses conducted within each of the two theoretical domains (rs of .21 and
      .38).

PMID- 11597057
TI  - Y2K affiliation, immediate pedestrian density, and helping responses to lost
      letters.
AB  - Of 75 letters "lost" in Florida, 41 were returned in the mail (the helpful
      response). Immediate pedestrian density was significantly related to nonhelping
      responses. The greater the number of subjects passing by a lost letter, the less
      likely any one of them would respond to it. The rates of return did vary with the
      addressees' affiliations. Returned responses for the affiliates, Y2K Arkbuilders
      and the Believers of God's Judgement Against Homosexuals: Y2K Millennium Bug,
      were substantially lower than for the affiliate, Y2K Computer Repair &
      Programming, Inc. Returns for the Believers of God's Judgement Against
      Homosexuals: Y2K Millennium Bug affiliate were significantly lower than for the
      Y2K Arkbuilders affiliate. Variables such as sex, race, and estimated age of
      subjects were not associated with helping to return a lost letter. The rate of
      return of lost letters is not the only important measure to be examined in
      studies using lost letters.

PMID- 11597058
TI  - Maternal question-asking of Japanese children with Down syndrome and with no
      disability.
AB  - In an extension of maternal question-asking to Japanese children during free play
      and at meal time each of 20 mother-child dyads was videotaped at home. The
      mothers of children with Down syndrome asked more questions during free play at
      meal time, and for the sum of these two. Also, they produced more requests for
      information during free play and for combined conditions and fewer clarification
      requests during free play. The results were compared to those of the previous
      study of Taiwanese mothers.

PMID- 11597059
TI  - Ethnic and sex differences in the predictive validity of the scholastic
      achievement test for college grades.
AB  - The predictive validity of SAT-Verbal and SAT-Mathematics scores for college
      grades was examined for males and females and for four ethnic groups in a
      nationally representative American sample. SAT scores "overpredicted" the grades
      of males and of Asians, Hispanics, and blacks, i.e., these groups did not obtain
      as good grades as would be predicted from their SAT scores. Conversely, SAT
      scores "underpredicted" the grades obtained by females and whites. i.e., these
      groups obtained better grades than would be predicted from their SAT scores. The
      possible explanations for these differential predictive validities are discussed.

PMID- 11597060
TI  - Adverse sexual and psychological effects of male infant circumcision.
AB  - A survey of the 35 female and 42 gay sexual partners of circumcised and genitally
      intact men, and a separate survey of 53 circumcised and 30 genitally intact men
      themselves, indicated that circumcised men experienced significantly reduced
      sexual sensation along with associated long-lasting negative emotional
      consequences.

PMID- 11597061
TI  - Peer versus authority as decision maker: are the demographics of the perceiver
      related to judgements of fairness?
AB  - In a role-playing study, 264 university students evaluated the fairness of
      procedures and outcomes used to punish a student for plagiarizing from a web
      site. Individuals reading the scenario gave the highest ratings of justice when
      the decision maker was a group of nonpeers (faculty), compared to when the
      decision maker was an individual or peer (student). Sex and self reported guilt
      of individuals reading the scenario also influenced their ratings of justice.

PMID- 11597062
TI  - Extraversion and the rebound effect after thought suppression.
AB  - 83 participants thought about a white bear before or after trying to suppress the
      idea. There was no rebound effect (more expression of white-bear thoughts after
      than before suppression) for either introverts or extraverts.

PMID- 11597063
TI  - Categories of success endorsed among religiously identified Seventh-Day Adventist
      students.
AB  - The focus of this study was to explore students' perceptions of success and how
      those perceptions may differ by sex, age, and education. Using Jensen and Towle's
      criteria (1991), 165 subjects qualified as "religious" out of the 247 respondents
      assessed. Given different theological emphases, it was hypothesized that this
      predominantly Seventh-day Adventist sample would perceive success differently
      than Jensen and Towle's sample and that there would be sex differences in
      religiosity which may interact with age, education, and self-reported grades.
      There were some sex differences in endorsement of success categories, which
      decreased as amount of education increased. A comparison between this
      predominantly Seventh-day Adventist group and Jensen and Towle's predominantly
      Latter-day Saint group indicates that there may be various value systems
      regarding success among religious denominations.

PMID- 11597064
TI  - Association of alcohol use and suicide in 27 nations of the world.
AB  - In 27 nations of the world, alcohol consumption predicted suicide rates, but
      changes in alcohol consumption did not predict changes in suicide rates.

PMID- 11597065
TI  - Formulas for combining summary statistics.
AB  - Formulas for computing the combined mean and standard deviation for any number of
      groups are presented. These formulas produce results that are different from the
      pooling (averaging) method.

PMID- 11597066
TI  - A revised psychoticism scale for the revised Eysenck personality questionnaire: a
      study among clergy.
AB  - The psychometric properties of an improved 6-item form of the Eysenck
      Psychoticism scale are examined among three samples of clergy, 1,227 Anglican
      clergywomen, 1,468 Roman Catholic male priests, and 1,321 male and female
      Methodist ministers. On the basis of these data the scale is commended for
      further use.

PMID- 11597068
TI  - Self-ratings of materialism and status consumption in a Malaysian sample: effects
      of answering during an assumed recession versus economic growth.
AB  - Consumers' self-assessments of materialism and status consumption may be
      influenced by external economic conditions. In this study, 239 Malaysian students
      were asked to describe their levels of materialism using Richins and Dawson's
      1992 Materialism scale and status consumption using Eastman, Goldsmith, and
      Flynn's 1999 Status Consumption Scale. Half the students were told to respond
      assuming that they were in an expanding economy, and half as if the economy was
      in a recession. Comparison of the groups' mean scores showed no statistically
      significant differences.

PMID- 11597067
TI  - Nurses' comprehension and recall process of a patient's message with double-bind
      information.
AB  - We examined nurses' comprehension and recall process of patients' passage with
      double-bind information. We focused on two modes of communication, tone of voice
      and content of speech. The experiment followed a 2 x 2 x 2 design with respect to
      listeners (nurse vs student), tone of voice (positive vs negative), and verbal
      content (positive vs negative). Subjects were 79 nurses who worked at the
      university hospital and 99 students who were studying at the Faculty of Nursing.
      Nurses and students were randomly divided into four subgroups; each was presented
      one of four professionally tape-recorded scripts representing one possible
      combination of tone of voice and verbal content on the part of a fictitious
      patient. Listeners then rated the passages on scales and were asked to recall the
      passages in detail. Listeners recalled and understood passages better when the
      modes of communication did not conflict. Accuracy in recall reflected
      comprehension of passages rather than the listener's feelings about the
      "patient," especially in double-bind situations. Listeners tended to judge the
      speaker's feelings by tone of voice rather than verbal content.

PMID- 11597069
TI  - Job stress and job satisfaction and their relation to neuroticism, type a
      behavior, and locus of control among Kuwaiti personnel.
AB  - The present study examined job stress and job satisfaction and their relation to
      measures of neuroticism, Type A behavior, and I-E locus of control as well as sex
      differences among Kuwaiti men (n= 189) and women (n = 210) employees. Women had
      significantly higher means on scales of job stress, neuroticism, and external
      locus of control, while men scored significantly higher on job satisfaction.
      Analysis yielded significant and positive correlations of job stress with
      neuroticism and locus of control of both men and women. Job satisfacrion scores
      correlated significantly but negatively with external locus of control for both
      sexes, while job satisfaction had a positive correlation with Type A behavior for
      women only. The significant correlation between job stress and job satisfaction
      was negative.

PMID- 11597070
TI  - Counseling female athletes: application of the stages of change model to avoid
      disordered eating, amenorrhea, and osteoporosis.
AB  - Research indicates that female athletes from all sports are at risk for
      developing disordered eating. amenorrhea, and resulting complications. These
      disorders, termed the female athlete triad by the American College of Sports
      Medicine, may lead to significant morbidity and mortality as well as medical and
      psychological problems. When female athletes feel pressured to fit a specific
      physical image, they may develop distorted body images and show disordered eating
      patterns. Menstrual dysfunction and premature osteoporosis may result from
      inadequate nutrition combined with excessive athletic training. Health
      professionals play important roles in prevention and treatment of these
      problematic behaviors. This paper examined the stages of the change behavior
      model and its use in addictive behaviors and provides theoretical applications of
      this model to reducing harmful behaviors in female athletes.

PMID- 11597071
TI  - An investigation of Gf-Gc theory in the older adult population: joint factor
      analysis of the Woodcock-Johnson-Revised and the Detroit Test of Learning
      Aptitude-Adult.
AB  - Researchers and clinicians are increasingly interested in the structure of
      intelligence among older adults. A joint factor analysis was conducted for 27
      subtests of the Woodcock-Johnson Psycho-Educational Battery-Revised and the
      Detroit Tests of Learning Aptitude-Adult for a sample of 50 persons ranging in
      age from 55 to 84 years (M=65.16 yr.). The results provide evidence for the
      latent factors speci fied by Gf-Gc theory in older adults, indicate which Gf-Gc
      factors are measured by subtests of the two batteries, and illustrate the
      necessity of cross-battery assessment to identify the full complement of Gf-Gc
      factors.

PMID- 11597072
TI  - Compulsive checking and selective processing of threatening information.
AB  - Threatening stimuli are processed differently from neutral ones by anxious and
      obsessive-compulsive subjects. In the present research, processing of threatening
      words was compared with that of neutral words for two groups of Italian students,
      one with high mean and one with low mean score on Checking, a subscale of the
      Padua Inventory. Two tests were given, a computerized version of the emotional
      Stroop task and a later recognition test under incidental learning conditions.
      The expected interference effect on the Stroop task for those scoring high on
      Checking was confirmed. These results suggest an association between compulsive
      checking and bias in the first automatic stages of processing of threatening
      stimuli.

PMID- 11597073
TI  - Anxiety among university students in South Africa.
AB  - Of 214 first-year students in an historically Black university, 17.8% scored in
      the Severe range on the Beck Anxiety Inventory. Sex and rural or urban background
      were not significant factors.

PMID- 11597074
TI  - FIRO-B, Machiavellianism, and teams.
AB  - A correlational study using the Mach IV and FIRO-B questionnaires examined the
      attitudes of 120 postgraduate and undergraduate students, the majority of whom
      had significant work experience. A curvilinear relationship observed between the
      FIRO-B and Mach IV scales calls into question an aspect of Will Schutz's
      prescription for interpersonal compatibility.

PMID- 11597075
TI  - Differences in lost letter responses from a seaside city.
AB  - Of 75 letters "lost" in the Florida Panhandle, 33 (44%) were returned in the mail
      by the finders (the altruistic response). Addressees' affiliations were
      significantly associated with different rates of return; fewer emotive
      Intercontinental Gay and Lesbian Outdoors Organization addressees were returned
      than nonemotive ones. The technique for power analysis by Gillett (1996) was
      applied to data from an earlier study and indicated our sample of 75 subjects
      would still yield a desired power level, i.e., 80, for the likely effect sizes.
      Statistical power was .83, and the effect was medium in size at .34.

PMID- 11597076
TI  - External validity of religiosity scales for a sample of southern students.
AB  - When mean scores on the Spiritual or Philosophical Domain of the Coping Resources
      Inventory for 96 university students of ages 20 to 47 years, were compared with
      means of the standardization sample, values fell outside the upper limit of the
      99% confidence interval, suggesting the scale may not have external validity for
      a sample of students.

PMID- 11597077
TI  - Roles of social support and social skills in the intercultural adjustment of
      Japanese adolescent sojourners in the USA.
AB  - Intercultural adjustment of Japanese high school students who sojourned in the
      United States for one year is the focus of the study. Building relationships with
      host nationals using limited English competency is the challenge that seems basic
      to successful adjustment to life in the USA. A path model was constructed in
      which English competence leads to better social skills, which in turn affects the
      amount of social support gained from host nationals. This model was tested
      through structural equation modeling, and the model's fit to the data was
      satisfactory. The predictive roles of English proficiency and personality were
      suggested in a supplementary analysis.

PMID- 11597078
TI  - Personality change as defensive responses of patients evaluated for liver
      transplant.
AB  - Patients affected by endstage liver disease and awaiting liver transplant suffer
      very stressful conditions. The aim of this study was to evaluate the person ality
      and behavioral responses of a group of liver transplant candidates, 95 men (M age
      50 yr.) and of a group of 18 normal men (M age 49 yr.). The 16 Personality Factor
      Questionnaire of Cattell, and the PSY Inventory for Behavioral Assessment were
      administered to assess personality and behavior. On the 16PF Questionnaire,
      patients had significantly different mean scores from normal subjects on Scale B-
      (low mental capacity), G (conformity), N (shrewdness), and Q1- (conservatism).
      They also showed a somewhat lower but not a statistically significant mean on
      Scale E (submissiveness). In addition, on the four second-order factors of the
      16PF (Anxiety, Control, Pathemia, and Extraversion) patients had a significantly
      higher mean on Control. With respect to PSY Inventors factors, patients showed
      impairment in energy, sleep, sexual disturbances, and obsessive behaviors. It
      appears these patients with endstage liver disease, who were evaluated for liver
      transplant, showed psychological regressive functioning, i.e., high control and
      dependency on medical staff, submissiveness, which are interpretable as defensive
      responses to upcoming transplant.

PMID- 11597079
TI  - The suicide rate in Austrian prisons: does it conform to sociological theory?
AB  - The Austrian prison suicide rate for 1950-1995 was shown to be associated in a
      similar manner to the social indicators of marriage, birth, and divorce rates as
      the suicide rate of Austrian males in the general population.

PMID- 11597080
TI  - Green, Mandel, Hotvedt, Gray, and Smith's study of 50 lesbian mothers and their
      children: inconsistencies in four published reports of the data.
AB  - The 1986 study of 50 lesbian mothers by Green, et al. may be the most influential
      concerning homosexual parenting. However, after setting standards for--and noting
      preliminary evidence of--gender identity confusion in 1980 and 1982, confirmatory
      findings in 1986 were not included in the report's abstract and conclusions.
      Numerous discrepancies in different published accounts of this study--including
      number of subjects and how, subjects were matched and analyzed--cannot be
      reconciled. The earliest reports were not cited in the final report which led to
      treatment in the literature as separate studies. The inconsistencies between the
      published accounts are substantive and numerous enough to recommend that the
      authors issue a complete and detailed report of the study.

PMID- 11597082
TI  - Relations of alexithymic characteristics with eating attitudes and hostility in
      female college students.
AB  - We examined the correlations of alexithymic characteristics with the expression
      of unfavorable feelings such as anger and hostility and abnormal eating attitudes
      and behaviors in a sample of 278 Japanese female college students. Mean scores on
      the Eating Attitude Inventory, MMPI Hostility, and State-Trait Anger Expression
      Inventory were significantly higher for female college stUdents with alexithymic
      characteristics than for those with nonalexithymic characteristics. Multivariate
      analysis of covariance indicated that the significant relationships between
      alexithymic characteristics and oral control of the eating attitudes were
      controlled by scores on anger-in and anger control, suggesting that anger-in and
      anger control may mediate the relationship between alexithymic characteristics
      and abnormal eating attitudes.

PMID- 11597081
TI  - Assessing the validity of the semantic differential portion of the Apperceptive
      Personality Test.
AB  - This study investigated the validity of the semantic differential portion of the
      Apperceptive Personality Test with 225 undergraduates who completed the Marlowe
      Crowne Social Desirability scale, actual-self and ideal-self semantic
      differential scales (e.g., Actual-self and ideal-self), and either the
      Apperceptive Personality Test or a modified version. A projected-self score was
      calculated using the semantic differential ratings of the hero(ine) character on
      the test, e.g., Projected self. A strong negative correlation indicated that, as
      the difference between the Ideal-self and Actual-self dereased, the difference
      between the Actual-self and Projected-self increased. Discriminant analyses
      indicated that highly guarded participants, e.g., high Social Desirability
      scores, showed more congruency between Ideal-self and Actual-self and less
      congruency between Actual-self ratings and Projected-self on the APT than did
      less guarded participants. When the difference scores incorporated only those
      semantic differential items that loaded on an Ealuative factor, the same result
      of discriminant analysis was found when participants who comleted the modified
      version were included. These findings support the validity of the test's semantic
      differential items and suggest that guardedness tends to promote more similarity
      between Actual-self and Ideal-self and less similarity between Actual-self and
      Projected-self.

PMID- 11597083
TI  - Attachment style, family and romantic relationships.
AB  - In 1987 Hazan and Shaver showed that patterns of romantic love reflected
      attachment styles. In an extension of that study with 39 men and 33 women in
      college (ages 18-36 years), this research shows that family relationships may
      also affect romantic relationships indirectly through their association with
      attachment styles.

PMID- 11597084
TI  - A preliminary study of subjective frequency estimates of words spoken in
      Cantonese.
AB  - A database is presented of the subjective frequency estimates for a set of 30
      Chinese homophones. The estimates are based on analysis of responses from a
      simple listening task by 120 University students. On the listening task, they are
      asked to mention the first meaning thought of upon hearing a Chinese homophone by
      writing down the corresponding Chinese characters. There was correlation of .66
      between the frequency of spoken and written words, suggesting distributional
      information about the lexical representations is generally independent of
      modality. These subjective frequency counts should be useful in the construction
      of material sets for research on word recognition using spoken Chinese
      (Cantonese).

PMID- 11597085
TI  - Evidence for concurrent validity of responses by survivors of hospital
      restructuring.
AB  - This study examined use of control, escape coping, and restructuring responses of
      survivors among hospital-based nursing staff who had survived significant
      hospital restructuring and downsizing. Four restructuring responses of survivors
      proposed by Mishra and Spreitzer in 1998 were considered: hopeful, obliging,
      cynical, and fearful. Data were collected from 744 nursing staff by
      questionnaire. Multiple regression analyses indicated greater use of active
      coping by more hopeful and more obliging survivors and greater use of escape
      coping by more cynical survivors.

PMID- 11597086
TI  - Stress in the relation between trait and state anxiety.
AB  - The relations of stress, trait anxiety, and state anxiety with cognitive
      performance are the central focus. Stress is conceived of as an external
      manipulation, trait anxiety as a relatively stable personality characteristic,
      and state anxiety as transient manifest feelings of insecurity. The influence of
      these factors on cognitive performance is considered. It was argued that the
      apparent interaction of stress and trait anxiety with cognitive performance can
      be traced to the interaction among stress, trait anxiety, and state anxiety. It
      was hypothesized that state anxiety increases more rapidly as a function of trait
      anxiety under stressful circumstances than neutral or rel atively reassuring
      circumstances. The negative relation between state anxiety and cog nitive
      performance is assumed to be constant irrespective of stress. Experimental evi
      dence supporting the latter supposition is presented. However, doubts are cast on
      classical intervention methods for invoking stress. Rather than assuming that
      these methods invoke stress, it is proposed that feelings of insecurity,
      associated with ambiguity, are determinants of experienced stress.

PMID- 11597087
TI  - Family strengths and the Kansas Marital Satisfaction Scale: a factor analytic
      study.
AB  - 20 new items were developed to measure six concepts of family strengths and were
      administered, along with the Kansas Marital Satisfaction Scale, to over 266
      married subjects as part of a larger survey of current and former members of the
      Christian Church (Disciples of Christ). A common factor analysis suggested that
      most of the items were associated with their expected factors, while reliability
      analyses indicated that most of the scales had acceptable estimates of internal
      consistency. The marital satisfaction items clearly were associated with their
      own factor and not other factors, providing support for the unidimensional nature
      of the Kansas Marital Satisfaction Scale and for its construct validity.

PMID- 11597088
TI  - Undergraduate students' understanding of division of fractions.
AB  - This exploratory study was designed to assess undergraduate students'
      understanding of division of fractions. A paper and pencil instrument was
      administered as a pre- and posttest to 59 undergraduate students who major in
      elementary education. Analysis by independent t test of written responses
      provided by students on the pre- and posttests showed lack of understanding, even
      postinstruction.

PMID- 11597089
TI  - Correlations between scores on attitudes toward celebrities and authoritarianism.
AB  - For a sample of 307 British participants a secondary analysis showed no
      significant correlations between scores on subscales or total attitude toward
      celebrities with those on authoritarianism for either sex.

PMID- 11597090
TI  - Recruitment of research participants from U.S. jury pools.
AB  - Psychological research is often criticized for routine use of a narrow and
      unrepresentative study population-college students. This study investigated the
      feasibility of recruiting research participants from U.S. jury pools, which by
      law must include a representative cross-section of the public. A questionnaire
      was mailed to the jury administrators in the 217 U.S. state court jurisdictions
      with populations of 250,000 or more. Court officials representing 79
      jurisdictions in 30 states and the District of Columbia returned surveys (36%
      response rate). In addition, respondents who indicated in the mail survey that
      their court had previously allowed outside investigators to recruit jurors also
      completed a follow-up telephone interview. While the majority of jurisdictions
      (61%) opposed participation of jurors in research, 31 jurisdic tions (39%) did
      not object to this practice. Only 8 of the nonopposed jurisdictions had been
      asked to host research, and 7 had agreed to do so. The jurisdictions that opened
      their jury pools to researchers employed a number of strategies to circumvent
      potential problems and generally reported that hosting research was a positive
      experience. Jury pools represent a viable and relatively untapped source of
      research participants. Many courts are open to the possibility of hosting
      research but have never been asked to do so. Both researchers and court officials
      should be reassured by the positive experiences of courts that have hosted
      research.

PMID- 11597091
TI  - Effects of altered instructions on WAIS-III Digit Symbol-coding subtest.
AB  - This study utilized 104 college students to assess the possibility that a
      performance increment would result on the WAIS-III Digit Symbol Coding subtest
      scores if instructions were modified to include the time allowed for completion.
      Compared with the standard instructions, this modification did not significantly
      change mean scores.

PMID- 11597092
TI  - Preliminary comparison of treatments of shoulder injuries using the FitLinxx
      computer feedback system and standard physical therapy.
AB  - Men and women suffering from various shoulder injuries (n = 28) were recruited to
      test the efficacy of a computer feedback system during physical therapy. Measures
      of physiological progress were statistically equivalent between the Standard
      Treatment and FitLinxx supported groups. Although compliance was uniformly high
      between groups, the FitLinxx-supported patients were more likely to continue
      exercise after termination of treatment. Considerably less total professional
      time was required for FitLinxx-supported therapy. Suggestions were made to
      replicate and extend the present preliminary findings.

PMID- 11597093
TI  - Career group counseling in undecided college female seniors' state anxiety and
      career indecision.
AB  - A sample of female college seniors experiencing career indecision participated in
      a career group counseling (n: 16), a wait-list control group (n: 8), and an
      additional career-counseling group (n: 11). Participants were administered the
      Career Decision Scale and the State-Trait Anxiety Inventory at pretest and
      posttest. Analysis of covariance of state anxiety scores and career indecision
      scores yielded significant main effects for treatment. Participants in the career
      counseling groups showed a decrease in scores on state anxiety and career
      indecision. Implications for research and female career group counseling are also
      discussed.

PMID- 11597094
TI  - Neuroscience and morality.
AB  - Humans are social animals who use specialized brain mechanisms to assess the
      actions of others. This system for social cognition can be studied by imaging
      techniques, and its damage can lead to inappropriate social and moral behavior.
      Neuroscience can thus enrich our understanding of behaviors traditionally thought
      to be outside the province of science.

PMID- 11597095
TI  - Recruitment of synaptic molecules during synaptogenesis.
AB  - The glutamatergic synapse is the main type of excitatory synapse in the mammalian
      brain. The formation of each glutamatergic synapse is associated with the
      recruitment of numerous (probably hundreds) different molecules and their
      assimilation into functional assemblies. Intense research has revealed the
      identity of many of these molecules, provided information as to interactions they
      are involved in, and offered clues as to their roles in synaptic function. Recent
      work has also begun to shed light on fundamental mechanisms underlying molecule
      recruitment to developing glutamatergic synapses. Current data indicate that the
      formation of presynaptic active zones-sites of neurotransmitter release-may be
      realized by the insertion of precursor vesicles containing multiple active zone
      components, possibly in pre-assembled form. The assembly of the postsynaptic
      reception apparatus, on the other hand, seems to occur via the sequential
      recruitment of molecules to the postsynaptic membrane and their assimilation in
      situ. Several molecules and mechanisms have been identified that display a
      capacity for inducing pre- or postsynaptic differentiation. These exciting
      findings are starting to provide a rudimentary framework for understanding key
      processes underlying the formation of glutamatergic synaptic connections.

PMID- 11597096
TI  - The central noradrenaline system and memory consolidation.
AB  - Long-term memory requires de novo protein synthesis and gene expression, which
      are mediated by certain intracellular signaling pathways. The noradrenaline (NA)
      system in the CNS is involved in a wide variety of neurological and psychological
      functions. In addition to previous pharmacological studies, a recent molecular
      genetic approach provides behavioral evidence for an essential role of the
      central NA system in long-term memory formation, particularly in memory
      consolidation. The potential cellular and molecular mechanisms underlying memory
      formation mediated by NA are discussed.

PMID- 11597098
TI  - On the function of dendritic spines.
AB  - Dendritic spines occupy a strategic position in the central nervous system, yet
      their function is still under debate. Over the past decades, many hypotheses have
      been put forward to explain the specific function of spines. Recently, imaging
      experiments have demonstrated that spines compartmentalize calcium, a role that
      appears necessary for input-specific forms of synaptic plasticity. In addition,
      it has been discovered that spine morphology is plastic over fast time scales and
      can be controlled by specific biochemical pathways. Also, several aspects of the
      spine's morphology appear to be intricately linked to its function. The authors
      review these recent data and incorporate them into a model for the function of
      dendritic spines in CNS circuits. In their proposal, spines serve to specifically
      connect sparse inputs and therefore minimize the wiring necessary in the CNS
      while maximizing connectivity. By virtue of the same design, spines isolate
      inputs and thus implement local learning rules. These rules appear only necessary
      with sparse inputs so these two functions are intimately related. Spines
      therefore would play a crucial circuit role, remarkably analogous to synaptic
      matrix elements of associative neural networks. This model highlights the
      economical, yet elegant, design of CNS circuits.

PMID- 11597097
TI  - Nogo: a molecular determinant of axonal growth and regeneration.
AB  - Following injury, axons of the adult mammalian central nervous system (CNS) fail
      to regenerate. As a result, CNS trauma generally results in severe and persistent
      functional deficits. The inability of CNS axons to regenerate is largely
      associated with nonneuronal aspects of the CNS environment that are inhibitory to
      axonal elongation. This inhibition is mediated by the glial scar, including
      reactive astrocytes, and by the myelin-associated neurite outgrowth inhibitors
      chondroitin sulfate proteoglycans, myelin-associated glycoprotein, and Nogo. Nogo
      is an integral membrane protein that localizes to CNS, but not peripheral nervous
      system, myelin. In vitro characterization of Nogo has demonstrated its function
      as a potent inhibitor of axon elongation. In vivo neutralization of Nogo activity
      results in enhanced axonal regeneration and functional recovery following CNS
      injury as well as increased plasticity in uninjured CNS fibers. These findings
      suggest that Nogo may be a major contributor to the nonpermissive nature of the
      CNS environment.

PMID- 11597099
TI  - Glutamate on demand: astrocytes as a ready source.
AB  - The past decade of studies has changed our view of the integrative capacities and
      roles of glia. A picture is emerging in which neurons and astrocytes, a subtype
      of glial cell, are in a continuous regulatory dialogue. Initial studies
      demonstrated that chemical transmitters, which are released from neurons, induce
      elevations of astrocytic calcium. Furthermore, stimulation of neuronal afferents
      at modest frequencies induces a calcium response in astrocytes that is graded
      with stimulation frequency. The consequence of this astrocytic calcium response
      is now beginning to be appreciated in that changes in calcium level can induce
      the release of the chemical transmitter glutamate from this nonneuronal cell.
      During the past few years, it has been shown that by releasing glutamate,
      astrocytes can regulate synaptic transmission and contribute to certain forms of
      synaptic plasticity. The roles played in information processing by this glial
      feedback loop remain to be determined. However, it is likely that the results of
      these recent studies will signal a new way of thinking about the nervous system,
      in which the glial cell comes to the forefront of our attention.

PMID- 11597100
TI  - Brain function, nonlinear coupling, and neuronal transients.
AB  - The brain can be regarded as an ensemble of connected dynamical systems and as
      such conforms to some simple principles relating the inputs and outputs of its
      constituent parts. The ensuing implications, for the way we think about, and
      measure, neuronal interactions, can be quite profound. These range from 1)
      implications for which aspects of neuronal activity are important to measure and
      how to characterize coupling among neuronal populations; 2) implication for
      understanding the emergence of dynamic receptive fields and functionally
      specialized brain architectures; and 3) teleological implications pertaining to
      the genesis of dynamic instability and complexity, which is necessary for
      adaptive self-organization. This review focuses on the first set of implications
      by looking at neuronal interactions, coupling, and implicit neuronal codes from a
      dynamical perspective. By considering the brain in this light, one can show that
      a sufficient description of neuronal activity must comprise activity at the
      current time and its recent history. This history constitutes a neuronal
      transient. Such transients represent an essential metric of neuronal interactions
      and, implicitly, a code employed in the functional integration of brain systems.
      The nature of transients, expressed conjointly in different neuronal populations,
      reflects the underlying coupling among brain systems. A complete description of
      this coupling, or effective connectivity, can be expressed in terms of
      generalized convolution kernels (Volterra kernels) that embody high-order or
      nonlinear interactions. This coupling may be synchronous, and possibly
      oscillatory, or asynchronous. A critical distinction between synchronous and
      asynchronous coupling is that the former is essentially linear and the latter is
      nonlinear. The nonlinear nature of asynchronous coupling enables the rich,
      context-sensitive interactions that characterize real brain dynamics, suggesting
      that it plays an important role in functional integration.

PMID- 11597101
TI  - Bilateral activity and callosal connections in the somatosensory cortex.
AB  - Earlier studies recording single neuronal activity in the postcentral
      somatosensory cortex of monkeys converged in suggesting that the bilateral
      receptive fields were related exclusively to the body midline including the
      trunk, perioral face, and oral cavity. These neurons were recorded mostly in the
      rostral part of the gyrus, areas 3b and 1. However, the authors recently found a
      substantial number of neurons with bilateral receptive fields on extremities,
      hand/digits, shoulders/arms, or legs/feet in the caudalmost part (areas 2 and 5)
      of the postcentral gyrus. The authors review these results and discuss functional
      implications of the bilateral representation in the postcentral somatosensory
      cortex.

PMID- 11597102
TI  - Gain modulation in the central nervous system: where behavior, neurophysiology,
      and computation meet.
AB  - Gain modulation is a nonlinear way in which neurons combine information from two
      (or more) sources, which may be of sensory, motor, or cognitive origin. Gain
      modulation is revealed when one input, the modulatory one, affects the gain or
      the sensitivity of the neuron to the other input, without modifying its
      selectivity or receptive field properties. This type of modulatory interaction is
      important for two reasons. First, it is an extremely widespread integration
      mechanism; it is found in a plethora of cortical areas and in some subcortical
      structures as well, and as a consequence it seems to play an important role in a
      striking variety of functions, including eye and limb movements, navigation,
      spatial perception, attentional processing, and object recognition. Second, there
      is a theoretical foundation indicating that gain-modulated neurons may serve as a
      basis for a general class of computations, namely, coordinate transformations and
      the generation of invariant responses, which indeed may underlie all the brain
      functions just mentioned. This article describes the relationships between
      computational models, the physiological properties of a variety of gain-modulated
      neurons, and some of the behavioral consequences of damage to gain-modulated
      neural representations.

PMID- 11597103
TI  - Neural network models of schizophrenia.
AB  - There is considerable neurobiological evidence suggesting that schizophrenia is
      associated with reduced corticocortical connectivity. The authors describe two
      neural network computer simulations that explore functional consequences of these
      abnormalities. The first utilized an "attractor" neural network capable of
      content-addressable memory. Application of a pruning rule that eliminated weaker
      connections over longer distances produced functional fragmentation and the
      emergence of localized, "parasitic" attractors that intruded into network
      dynamics. These pathologies generally were expressed only when input information
      was ambiguous and provide models for delusions and cognitive disorganization. A
      second neural network simulation examined effects of corticocortical pruning in a
      speech perception network. Excessive pruning caused the network to produce
      percepts spontaneously, that is, in the absence of inputs, thereby simulating
      hallucinations. The "hallucinating" network also demonstrated subtle impairments
      in narrative speech perception. A parallel study of human patients found similar
      impairments when comparing hallucinating patients with nonhallucinating patients.
      In addition, the authors have used transcranial magnetic stimulation (TMS) to
      directly probe speech perception neurocircuitry in patients with these
      hallucinations. As predicted by the neural network model, the authors confirmed
      that "suppressive" low-frequency TMS reduces auditory hallucinations. Neural
      network simulations provide empirically testable concepts linking
      phenomenological, cognitive, and neurobiological findings in schizophrenia.

PMID- 11597104
TI  - Neural plasticity after human spinal cord injury: application of locomotor
      training to the rehabilitation of walking.
AB  - Recovery of locomotion has been considered unattainable following a clinically
      complete or severe incomplete spinal cord injury even after conventional therapy.
      However, the locomotion of spinal animals can be improved by training that
      provides complex temporal patterns of sensory information related to stepping
      that is interpreted by the spinal cord. This review discusses the evidence that
      suggests human spinal networks can integrate and interpret complex sensory
      signals to produce functional efferent output and adapt to repetitive training.
      Locomotor training, a new rehabilitative approach, is based on principles that
      promote the movement of limbs and trunk to generate sensory information
      consistent with locomotion to improve the potential for the recovery of walking
      after neurologic injury.

PMID- 11597105
TI  - Cushing's contributions to neuroscience, part 2: Cushing and several dwarfs.
AB  - Harvey Cushing revolutionized modern neurosurgery and pioneered the field of
      neuroendocrinology. This second of a two-part series on Harvey Cushing's
      contributions to neuroscience discusses his pivotal discoveries of the function
      and clinical disorders of the anterior pituitary. A review of his 20-year
      obsession with the pituitary reveals Cushing's ingenuity, keen sense of
      observation, and persistent stubborness. His enthusiasm to test his ideas,
      however, led to risky experimentation. Despite his foibles, his work opened up
      new frontiers of research for a number of investigators, whose efforts resulted
      in the identification of specific pituitary hormones, the hypothalamic regulation
      of the pituitary, and the practical applications of endocrinology.

PMID- 11597106
TI  - Evaluation of remediation performance and cost for field-scale single-phase
      microemulsion (SPME) flushing.
AB  - Pump-and-treat strategies employed to contain contaminant plumes have been
      demonstrated to be inefficient, and often ineffective, for remediation of
      aquifers contaminated by nonaqueous phase liquids (NAPLs). This has prompted the
      development of alternative technologies to provide enhanced remediation of NAPL
      source zones. The results reported here are from a solubilization study wherein
      the objective was to achieve high NAPL remediation efficiencies using a low
      concentration of chemical additives in the flushing solution. A
      surfactant/alcohol mixture was used to generate a Winsor Type I system, where the
      NAPL was solubilized and transported as a single-phase microemulsion (SPME). For
      the SPME process, only 5.5 wt% of the flushing solution comprised chemical
      additives. The costs associated with this project are discussed and approaches
      aimed at reducing costs are suggested.

PMID- 11597107
TI  - Feasibility of in situ NAPL-contaminated aquifer bioremediation by biodegradable
      nutrient-surfactant mix.
AB  - Entrapped non-aqueous liquid phase (NAPL) pollutants (e.g., fuels) constitute one
      of the biggest current problems in the bioremediation efforts of contaminated
      soil and aquifers worldwide. On site, in situ surfactant-enhanced bioremediation,
      in the presence of sufficient nutrients and dissolved oxygen, has the potential
      of becoming the remediation method of choice in terms of both technological and
      economical feasibility. This approach was applied in our lab-scale column-based
      flow system with the aid of which an optimized, below CMC, of biodegradable
      surfactant-nutrient surfactant mix has been established for the best
      solubilization/ mobilization of NAPL (hexane, toluene, kerosene and their
      mixtures as "representatives") in sandy matrix. For kerosene, the highest f
      values (the enhancement factors) were obtained for the systems containing either
      the amphoteric cocoamphodiacetate or the anionic linear dodecylbenzene sulfonate
      (0.1-0.3 g/L) with one or both the nutrient-surfactants L and B (0.05 g/L).

PMID- 11597108
TI  - Three dimensional numerical modeling of multiphase flow and transport.
AB  - The coupled multiphase flow and transport problem is solved by the finite element
      method, using linear three-dimensional tetraeder elements. The three-phase flow
      problem is solved simultaneously for the fluid pressures. The strong
      nonlinearities are treated with a Newton-Raphson iteration scheme with
      relaxation. Due to the kinetic of interphase mass transfer and reactions, the
      equations for water, gas, and solid phase concentrations are strongly coupled.
      Therefore, both transport equations for water and gas are solved simultaneously,
      while the equation for the solid phase is solved directly. The numerical model
      was tested with analytical, quasi-analytical and other numerical models. After
      the verification first applications were performed.

PMID- 11597109
TI  - Comparison of ex situ and in situ bioremediation of unsaturated soils
      contaminated by petroleum.
AB  - The most feasible bioremediation technologies of unsaturated soils contaminated
      by Petroleum are (1) the on-site controlled remediation of the excavated
      contaminated plume in the contained system; and (2) the in situ sub-surface,
      highly controlled process in which nutrients and microbes or air are injected
      into the plume volume via a grid of wells and reversing the direction of the
      pumping. The detailed results of ex situ (controlled aerobic bioremediation) of
      ten sites with differing petroleum contamination and four in situ cases are
      reported and compared. It is concluded, that bioremediation of petroleum
      contaminated soil is an effective, safe and economically feasible remediation
      technique for the remediation of such contaminated sites, contingent on the
      providing of the site-specific appropriate conditions. However, the
      biodegradation rate of the NAPL is more variable in the in situ than in the ex
      situ aerobic process, correlating best in the latter with the molecular weight of
      the petroleum contaminants.

PMID- 11597110
TI  - A case study of DNAPL remediation in northeastern Brazil.
AB  - Aquifer restoration in the United States is recognized as a technically
      challenging objective when dense non-aqueous phase liquids (DNAPLs) are present
      (1). In fact, only a few aquifers impacted by DNAPLs have been restored. Factors
      that have typically contributed to the lack of successful aquifer restoration
      include the chemical properties of the DNAPL, the physical properties of the
      aquifer, the absence of cost-effective technologies, and an incomplete or
      inaccurate development of a conceptual hydrogeological model for the site. In
      Latin America, environmental studies historically have been related to biological
      quality of surface water and groundwater. Recently, the U.S. and Canada have
      experienced an increased influx of foreign students and professionals interested
      in studying specialized courses in environmental engineering, or participating in
      conferences. This exposure to current topics has strengthened the awareness of
      these professionals regarding groundwater contamination from gasoline-derived
      compounds and chlorinated solvents. As a result of this increased awareness,
      Latin American hydrogeologists and environmental regulators have been able to
      recognize the potential problems that could result from DNAPL spills that may
      impact groundwater and have learned to approach them using locally available
      technology and resources. A case study of such an example is presented below.

PMID- 11597111
TI  - Humic acids enhanced removal of aromatic hydrocarbons from contaminated aquifers:
      developing a sustainable technology.
AB  - Contamination by gasoline and diesel fuels is a threat to groundwater resources.
      Polynuclear aromatic hydrocarbons (PAHs) which can represent up to 60% of volume
      in diesel fuels are of particular concern because many of them are carcinogenic
      and they are persistent, especially in oxygen-limited environment. Despite the
      development of alternative approaches, pump and treat continues to be the leading
      technology for the remediation of groundwater contaminated by gasoline and diesel
      fuels. The efficiency of this technology is however limited by the low solubility
      of the aromatic hydrocarbons. The objective of this study was to investigate the
      influence of humic acids on the removal of aromatic hydrocarbons from petroleum
      products in groundwater aquifers and to evaluate the potential use of humic
      acids, as a cost effective additive, in groundwater and soil remediation. In
      order to prove the feasibility of using humic acid in the field, a pilot scale
      experiment was conducted in a model aquifer with a very dense monitoring network,
      providing controlled conditions only possible in a semi-artificial system. In
      addition, different sources of humic acids were compared with surfactants for
      their ability to bind PAHs.

PMID- 11597112
TI  - Gas phase reduction of chlorinated VOCs by zero valent iron.
AB  - The removal of trichloroethylene (TCE) by reduction with elemental iron was
      examined in batch reactors representing three phase gaseous systems (Fe0 (solid),
      water vapor + TCE vapor + air mixture (gaseous), and condensed water on Fe0
      surface (aqueous)) and two phase aqueous systems (Fe0 (solid), water (aqueous))
      as the reaction medium. Two separate removal mechanisms were found for TCE
      removal in the gas phase reactors: (1) adsorption onto the Fe0 surface under low
      relative humidity (RH), and (2) reaction with Fe0 to form other organic
      compounds, such as ethylene, isomers of dichloroethylene, and vinyl chloride
      under 100% RH conditions in the gas phase. The adsorption of TCE vapor onto the
      Fe0 surface was fast initially and highest at low temperatures. The reduction
      reaction of TCE in the gas phase was first order with respect to the TCE
      concentration remaining in the gas phase under conditions of 100% RH at 15, 22,
      and 35 degrees C, and the observed reaction rate constant (kobs) exhibited a
      maximum at elevated temperatures. The estimated kobs values for the degradation
      of dissolved TCE in aqueous systems were the same order of magnitude with the
      rate constants in the gas phase and exhibited an increasing rate at higher
      temperatures. The results suggest that Fe0 represents an economical choice for
      vapor phase barriers to limit the spread of contaminants in soil gas and reduce
      fugitive air emissions from contaminated sites.

PMID- 11597113
TI  - Feasibility of on-site bioremediation of loam soil contaminated by diesel oil.
AB  - This study originated from an accidental event of diesel oil contamination in a
      loam soil area of 7,000 m2. Approximately a volume of 1,300 m3 of diesel oil was
      released into the environment. Reclamation of the contaminated soil by on-site
      bioremediation was selected as the most appropriate treatment method. A major
      concern was associated with the nature of the local loam soil. Loam has a very
      low hydraulic conductivity and very quickly becomes impermeable after its contact
      with water. The bioremediation approach incorporated excavation of the
      contaminated soil, mixing it with an agent, which increased its permeability.
      Following this preliminary treatment came the construction of bioreactors as a
      suitable environment of nutrients, moisture, dissolved oxygen, and enriched
      culture of microorganisms, which enabled breakdown of the diesel oil. This case
      study indicated that the target of 99% of diesel oil clean up could be achieved
      by using the technology of on-site bioremediation. The selected treatment method
      was found to be technologically and economically feasible. However, some
      improvement in the application of the basic treatment approach might increase the
      bioremediation efficiency.

PMID- 11597114
TI  - Remediation of NAPL-contaminated aquifers: is the cure worth the cost?
AB  - Millions of dollars are spent in the United States each year to design,
      construct, and operate systems intended to remediate groundwater impacted by
      dense non-aqueous phase liquids (DNAPLs), such as trichloroethlene (TCE) and
      tetrachloroethene (PCE), or light non-aqueous phase liquids (LNAPLs), such as
      gasoline, diesel, and jet fuel. However, several recent studies suggest that many
      of these groundwater remediation systems may operate for decades without
      restoring groundwater to background conditions. This paper examines the potential
      economic impacts of continuing the current regulatory approach to remediation of
      NAPL-contaminated aquifers versus considering regionally contaminated aquifers as
      large storage basins instead of pristine resources. Treating water at the point
      of extraction when needed, provides an equivalent benefit and may be more
      practical and cost effective than attempting to restore aquifers to background
      conditions at the point of contamination.

PMID- 11597115
TI  - What is sustainable remediation?

PMID- 11597116
TI  - Quantification of elastin from the mouse lung during postnatal development.
AB  - Elastic fibers play a vital role in secondary septal development during the
      process of lung alveolization. The authors present a quantitative study by image
      analysis and by high-performance liquid chromatography (HPLC) of the mouse
      lungs'elastic fibers throughout postnatal development. Five mice from birth up to
      the 21st day of postnatal development and on the 30th day of life were used
      daily. Their left lungs were collected and processed for observation under light
      microscopy. The staining was carried by a modification of the Gomori technique.
      The right lung of each animal was processed for elastin quantification by HPLC.
      Analysis by linear regression of the two methods' results showed there was a
      significant positive linear correlation. With this methodology of staining and
      image analysis we evaluated the normal establishment of the elastic network of
      the respiratory portion of the lung from birth to adult life. We now have a good
      model for studying the variations induced by exogenous agents in the synthesis
      and degradation of the pulmonary elastic fibers.

PMID- 11597117
TI  - Human alveolar long-term clearance of ferromagnetic iron oxide microparticles in
      healthy and diseased subjects.
AB  - Monodisperse ferrimagnetic microparticles (Fe3O4) with 1.3 microm geometric
      diameter were inhaled to study alveolar long-term clearance in healthy and
      diseased human subjects. Nineteen younger (age 20 to 39 years) and 20 older (age
      40 to 65 years) healthy volunteers participated in the study as well as 15
      patients with sarcoidosis (SAR), 12 patients with idiopathic pulmonary fibrosis
      (IPF), and 15 patients with chronic obstructive bronchitis (COB). In each group
      the subjects were divided into never smokers (NS) and active smokers (S).
      Clearance was measured by magnetopneumography (MPG) for 300 days after
      inhalation. In COB, 50% of the deposited particles were removed from the lungs
      after 2 days, indicating high bronchial deposits due to bronchial obstructions.
      In healthy NS, only 10% of the particles were removed after 2 days and cigarette
      smoking enhanced the fraction of fast-cleared particles. In subjects who smoked,
      slow clearance was significantly impaired (P < . 02). Clearance half-lives (in
      days) for younger, healthy, NS were 124 +/- 66 (mean +/- SD) compared to 220 +/-
      74 for S. Similarly for older subjects, the timeswere 162 +/- 120 for NS and 459
      +/- 334 for S. The impairment of alveolar clearance due to cigarette smoking
      increases by 5.7 +/- 1.3 days/pack-year (P < .01). Alveolar clearance was
      impaired in SAR and in IPF; half-lives were 275 +/- 109 days (P < .05) and 756 +/
      345 days (P < .02), respectively, compared to healthy NS. Most COB patients were
      ex-smokers, their long-term clearance was 240 +/- 74 days, which is more than
      healthy NS (P < .01), but less than healthy S and might indicate a recovery of
      alveolar clearance. In view of studies using totally inert particles like Teflon,
      we conclude that the lung clearance measured with iron oxide tracer particles
      primarily reflects clearance by intraphagosomal particle dissolution within
      alveolar macrophages, which is impaired by cigarette smoke consumption and in
      patients.

PMID- 11597118
TI  - Programmed cell death in normal fetal rat lung development.
AB  - Lung development is a coordinated process regulated by the interactions of
      extracellular and intracellular factors, yet little is known about the process of
      programmed cell death during lung development. To study this question, we
      examined fetal rat lung from the pseudoglandular period (gestational day 15) to
      the day of birth (gestational day 21) using BrdU incorporation into DNA as a
      proliferative marker, while in parallel examining several markers of programmed
      cell death including terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL), DNA "laddering, " and expression of programmed cell death
      pathway proteins. Cell proliferation was ongoing throughout fetal days 15 to 21
      with a decrease in proliferation over days 20 and 21. Programmed cell death in
      fetal lung also appeared to be present at all ages examined, but demonstrated 2
      peaks of activity at fetal days 15 and 18 to 20. Bcl-XL expression was detected
      on fetal days 15 to 21, with diminished expression on days E15 to E18. Cleaved
      poly(ADP-ribose)polymerase (PARP), activated caspase-3, Bax, and Bad were
      increased on days 18 to 20. We conclude that proliferation is the primary process
      driving fetal lung development with programmed cell death occurring throughout
      the lung developmental process to refine structural remodeling.

PMID- 11597119
TI  - The role of leukocytes during acute phase inflammation in crystalline silica
      induced lung injury.
AB  - Silicosis is characterized by progressive granulomatous and fibrogenic response
      in the lung. Inhaled crystalline silica (Qt) induces activation of pulmonary
      macrophages and leukocyte infiltration in the lung of Qt-treated animals. We
      investigated the role of leukocyte infiltration and L-selectin during the acute
      phase of inflammation in developing chronic lung injury in Qt-treated rats.
      Seventy Wistar male rats were treated with a single transtracheal instillation of
      Qt (25 mg/kg). Rats were treated intraperitoneally with anti L-selectin
      monoclonal antibody (mAb), F(ab')2 HRL-3 (HRL-3, a blocking mAb), or RF(ab')2 HRL
      2 (HRL-2, a non-blocking mAb)for 4 days before and after Qt injection.
      Administration of HRL-3 reduced approximately 50% of leukocyte infiltration in
      the BAL, whereas HRL-2 treatment prior to Qt stimulation showed time-dependent
      increase of BAL leukocytes. CINC and GRO levels as well as peripheral blood cell
      counts were similar in HRL-2- or HRL-3-treated animals in the first 4 days of the
      study. Three months after Qt treatment, extensive granuloma-containing
      macrophages and leukocytes developed in the lung of the HRL-3-treated rats as
      compared with the HRL-2-treated rats. Ratio of CD4+ to CD8+ T cells in granulomas
      did not differ between the HRL-3 and HRL-2 groups. Results suggest that an early
      phase of leukocyte activation was diminished by blocking L-selectin with the
      antibody, but treatment with anti-L-selectin increased the formation of
      granulomas in the Qt-treated rats.

PMID- 11597120
TI  - KGF and HGF are growth factors for mesothelial cells in pleural lavage fluid
      after intratracheal asbestos.
AB  - Mesothelial cells proliferate soon after asbestos deposition in the lung. The
      present study investigates whether the known mesothelial cell mitogens
      keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are present
      in the lung and specifically in the pleural cavity during the phase of
      mesothelial cell growth. Rats received 1 mg crocidolite asbestos in 0.5 mL water
      by intratracheal instillation and were killed up to 2 weeks later; tritiated
      thymidine was injected 1 hour before death. Bronchoalveolar lavage (BAL) and
      pleural lavage (PLL) were performed. Increased inflammatory cell numbers and
      protein levels were found in BAL but also in PLL at 1 day after asbestos
      deposition. In lung sections, labeling of mesothelial cells increased > 10-fold
      at day 1 and stayed above normal for 1 week. During this period, the levels of
      HGF and KGF were significantly raised in both BAL and PLL fluids. The PLL fluid
      had mitogenic activity for mesothelial cells in culture and this effect was
      significantly reduced by antibodies to HGF and KGF. The results indicate that
      fiber deposition in the airspaces rapidly induces lung injury and inflammation,
      in which growth factors for mesothelial cells KGF and HGF are secreted. These
      factors reach the pleural cavity at the time when mesothelial cell proliferation
      occurs. It is possible that the activated, dividing mesothelial population may
      then be more susceptible to DNA damage by any translocated fibers.

PMID- 11597121
TI  - TNF-alpha enhanced allergic sensitization to house dust mite in brown Norway
      rats.
AB  - We have recently demonstrated that pulmonary exposure to residual oil fly ash
      (ROFA) resulted in enhanced sensitization to house dust mite (HDM) and augmented
      the development of allergic lung disease after allergen challenge. This effect
      was associated with increased tumor necrosis factor alpha (TNF-alpha), a
      macrophage- and epithelial cell-derived cytokine that promotes granulocyte
      migration to the lung. The present study examined whether exogenous
      administration of TNF-alpha enhances sensitization to HDM. One day prior to
      pulmonary sensitization with 10 microg HDM (5 microg each on days 1 and 3),
      female Brown Norway rats were instilled via the trachea with either 2.0 microg
      recombinant rat TNF-alpha, 2.0 microg bovine serum albumin (BSA), or 1,000 microg
      ROFA, and were challenged with 10 microg HDM 14 days later. Antigen-induced
      immediate bronchoconstriction responses, antigen-specific immunoglobulin E (IgE)
      titers, lymphocyte proliferation, (cytokines (TNF-alpha and interleukin [IL]-13),
      and eosinophils were elevated in rats treated with ROFA or TNF-alpha compared
      with BSA-treated controls after HDM challenge. Intratracheal administration of
      anti-TNF-alpha monoclonal antibody during ROFA exposure did not reduce ROFA
      enhanced lymphocyte proliferation or IgE titers, but had a trend for reduced
      pulmonary inflammation. This study demonstrates that TNF-alpha has similar
      adjuvant activity as ROFA, but other factors may fulfill this function when TNF
      alpha activity is blocked.

PMID- 11597122
TI  - Quercetin abrogates taxol-mediated signaling by inhibiting multiple kinases.
AB  - Cell cycle block in G(2)/M initiates apoptosis, but the mechanism of this
      signaling cascade are largely unknown. The microtubule-perturbing agent Taxol has
      multiple effects on this signaling pathway and is a potent inducer of apoptosis.
      The specific pathways activated by low, clinically relevant concentrations of the
      drug are still largely unknown and are dependent on cell type and drug
      concentration. In this work, we have investigated why HeLa cells respond to Taxol
      by undergoing complete apoptosis, whereas MCF-7 cells remain in an intermediate
      phase with reduced death. Three phases were distinguished in these apoptotic
      pathways. The initial phase characterized by cellular detachment is followed by a
      second phase which includes the onset of apoptotic morphology, and p38 and Bcl-2
      phosphorylation. These two phases are common to both cell lines. HeLa cells then
      proceed to the third and final execution phase, which culminates in death,
      whereas MCF-7 cells do not progress. Interestingly, the isoflavonoid Quercetin, a
      known general kinase inhibitor and an antioxidant, was able to prevent the onset
      of Taxol-induced cellular detachment and to protect from cell death. Moreover, it
      blocked Taxol-induced phosphorylation of p38 and Bcl-2, and prevented a Taxol
      induced change in relative mobility of the apoptosis signal-regulating kinase 1
      (Ask1). Our data elucidate the signaling pathways activated by Taxol at low
      clinically relevant concentrations.

PMID- 11597123
TI  - Midkine binds to 37-kDa laminin binding protein precursor, leading to nuclear
      transport of the complex.
AB  - Midkine (MK) is a heparin binding multifunctional protein that promotes cell
      survival and cell migration. MK was found to bind to 37-kDa laminin binding
      protein precursor (LBP), a precursor of 67-kDa laminin receptor, with K(d) of 1.1
      nM between MK and LBP-glutathione-S-transferase fusion protein. The binding was
      inhibited by laminin, anti-LBP, amyloid beta-peptide, and heparin; the latter two
      are known to bind to MK. In CMT-93 mouse rectal carcinoma cells, LBP was mostly
      located in the cytoplasm as revealed by immunostaining with anti-LBP antibody.
      That a portion of LBP or 67-kDa laminin receptor was located at the surface of
      these cells was verified by inhibition of cell attachment to laminin-coated
      dishes by anti-LBP antibody. When MK was added to culture medium of these cells,
      a part of LBP migrated to the nucleus. The movement occurred concomitantly with
      nuclear transport of biotin-labeled MK. These findings suggested that the binding
      of MK to LBP caused nuclear translocation of the molecular complex.

PMID- 11597124
TI  - Growth factor regulation of smooth muscle actin expression and contraction of
      human articular chondrocytes and meniscal cells in a collagen-GAG matrix.
AB  - Recent work has demonstrated that human articular chondrocytes and meniscus cells
      can express the gene for a contractile actin isoform, alpha-smooth muscle actin
      (SMA), in vivo. The objective of the present study was to evaluate the effects of
      two growth factors, transforming growth factor (TGF)-beta1 and platelet-derived
      growth factor (PDGF)-BB, on the SMA content of these cells and their contraction
      of a collagen-glycosaminoglycan (GAG) analog of extracellular matrix in vitro.
      TGF-beta1 was found to markedly increase SMA content of the cells and PDGF-BB
      decreased SMA expression, with both findings achieving statistical significance.
      A notable finding was the increased contraction of the collagen-GAG matrix
      induced by TGF-beta1 and the decrease in contraction resulting from PDGF-BB
      treatment, indicating a causal relationship between expression of SMA and the
      contractility of the cells. A novel cell force monitor, employed to estimate the
      force exerted per cell, demonstrated a higher force exerted by the TGF-beta1
      treated cells. The findings demonstrate that the expression of SMA by articular
      chondrocytes and meniscal cells and their associated contractile behavior can be
      regulated by selected growth factors. This work provides a foundation for the
      rational investigation of the mechanisms underlying SMA-enabled contraction of
      these cell types and the control of this behavior in tissue engineering.

PMID- 11597125
TI  - Inhibition of anchorage-independent cell growth, adhesion, and cyclin D1 gene
      expression by a dominant negative mutant of a tyrosine phosphatase.
AB  - PTP-S4/TC48 protein tyrosine phosphatase is localized in the nuclear and
      cytoplasmic membranes. To investigate the role of PTP-S4 in cell growth,
      adhesion, and transformation, normal and a catalytically inactive mutant form of
      this phosphatase were expressed in polyoma virus-transformed F111 fibroblast cell
      line, PyF. Expression of mutant PTP-S4 in PyF cells resulted in strong inhibition
      of anchorage-independent growth in soft agar but had no significant effect on
      growth in liquid culture. Tumor formation in nude mice was also reduced by mutant
      PTP-S4. Expression of normal PTP-S4 in PyF cells significantly increased
      anchorage-independent cell growth and tumor formation in nude mice.
      Overexpression of catalytically inactive mutant of PTP-S2/TC45 (a splice variant
      of PTP-S4 that is nuclear) did not inhibit anchorage-independent growth of PyF
      cells. Mutant PTP-S4-expressing cells were inhibited in adhesion and spreading on
      tissue culture plates compared to control cells. Expression of mutant PTP-S4 in
      PyF cells reduced the levels of cyclin D1 and cyclin A mRNA, whereas cyclin D2
      mRNA level was not affected significantly. Expression of antisense cyclin D1
      strongly inhibited anchorage-independent growth. Inhibition of anchorage
      independent growth by mutant PTP-S4 was overcome to a large extent by
      coexpression of cyclin D1. These results suggest that mutant PTP-S4 inhibits
      anchorage-independent growth and adhesion of polyoma virus-transformed cells by
      interfering with the normal function of PTP-S4 upstream of cyclin D1 gene
      expression.

PMID- 11597126
TI  - The cytoplasmic/transmembrane domain of dipeptidyl peptidase IV, a type II
      glycoprotein, contains an apical targeting signal that does not specifically
      interact with lipid rafts.
AB  - We investigated the signals involved in the apical targeting of dipeptidyl
      peptidase IV (DPP IV/CD26), an archetypal type II transmembrane glycoprotein. A
      secretory construct, corresponding to the DPP IV ectodomain, was first stably
      expressed in both the enterocytic-like cell line Caco-2 and the epithelial kidney
      MDCK cells. Most of the secretory form of the protein was delivered apically in
      MDCK cells, whereas secretion was 60% basolateral in Caco-2 cells, indicating
      that DPP IV ectodomain targeting is cell-type-dependent. A chimera (CTM-GFP)
      containing only the cytoplasmic and transmembrane domains of mouse DPP IV plus
      the green fluorescent protein was then studied. In both cell lines, this chimera
      was preferentially expressed at the apical membrane. By contrast, a secretory
      form of GFP was randomly secreted, indicating that GFP by itself does not contain
      cryptic targeting information. Comparison of the sequence of the transmembrane
      domain of DPP IV and several other apically targeted proteins does not show any
      consensus, suggesting that the apical targeting signal may be conformational.
      Neither the DPP IV nor the CTM-GFP chimera was enriched in lipid rafts. Together
      these results indicate that, besides the well-known raft-dependent apical
      targeting pathway, the fate of the CTM domain of DPP IV may reveal a new raft
      independent apical pathway.

PMID- 11597127
TI  - TNFalpha enhances the DNA single-strand breakage induced by the short-chain lipid
      hydroperoxide analogue tert-butylhydroperoxide via ceramide-dependent inhibition
      of complex III followed by enforced superoxide and hydrogen peroxide formation.
AB  - Treatment of U937 cells with nontoxic concentrations of TNFalpha increased the
      DNA strand scission induced by a short-chain lipid hydroperoxide analogue, tert
      butylhydroperoxide. The following lines of evidence suggest that the enhancing
      effects of TNFalpha are mediated by inhibition of complex III and by the ensuing
      formation of superoxides and hydrogen peroxide: (a) the effects of TNFalpha were
      mimicked by the complex III inhibitor antimycin A; (b) the effects of TNFalpha,
      or antimycin A, were abolished by the complex I inhibitor rotenone, or by
      myxothiazol, an agent which inhibits the electron flow from the reduced coenzyme
      Q to cytochrome c(1) and therefore prevents ubisemiquinone formation; (c) the
      effects of TNFalpha, or antimycin A, were not observed in respiration-deficient
      cells; and (d) the effects of TNFalpha, or antimycin A, were sensitive to
      catalase. The TNFalpha-dependent inhibition of complex III appears to be mediated
      by ceramide. Three lines of evidence support this inference: (a) a synthetic cell
      permeable ceramide analogue reproduced all the effects of TNFalpha, (b) TNFalpha
      promoted the formation of ceramide via a mechanism sensitive to inhibition of
      sphingomyelinases by tricyclodecan-9-yl-xanthogenate and imipramine, and (c) the
      TNFalpha-mediated enhancement of the tert-butylhydroperoxide-induced DNA-damaging
      response was prevented under conditions in which ceramide formation was
      inhibited.

PMID- 11597128
TI  - Cocompartmentalization of p53 and Mdm2 is a major determinant for Mdm2-mediated
      degradation of p53.
AB  - The product of the Mdm2 oncogene directly interacts with p53 and promotes its
      ubiquitination and proteasomal degradation. Initial biological studies identified
      nuclear export sequences (NES), similar to that of the Rev protein from the human
      immunodeficiency virus, both in Mdm2 and p53. The reported phenotypes resulting
      from mutation of these NESs, together with results obtained using the nuclear
      export inhibitor leptomycin B (LMB), have led to a model according to which
      nuclear export of p53 (via either the NES of Mdm2 or its own NES) is required for
      efficient p53 degradation. In this study we demonstrate that Mdm2 can promote
      degradation of p53 in the nucleus or in the cytoplasm, provided both proteins are
      colocalized. We also investigated if nuclear export is an obligate step on the
      p53 degradation pathway. We find that (1) when proteasome activity is inhibited,
      ubiquitinated p53 accumulates in the nucleus and not in the cytoplasm; (2) Mdm2
      with a mutated NES can efficiently mediate degradation of wild type p53 or p53
      with a mutated NES; (3) the nuclear export inhibitor LMB can increase the steady
      state level of p53 by inhibiting Mdm2-mediated ubiquitination of p53; and (4) LMB
      fails to inhibit Mdm2-mediated degradation of the p53NES mutant, demonstrating
      that Mdm2-dependent proteolysis of p53 is feasible in the nucleus in the absence
      of any nuclear export. Therefore, given cocompartmentalization, Mdm2 can promote
      ubiquitination and proteasomal degradation of p53 with no absolute requirement
      for nuclear to cytoplasmic transport.

PMID- 11597129
TI  - Cloning and characterization of Plx2 and Plx3, two additional Polo-like kinases
      from Xenopus laevis.
AB  - Members of the family of Polo-like kinases are implicated in the regulation of
      cell cycle progression in all eukaryotes. In Xenopus laevis, only one member of
      this family, Plx1, has previously been described. Here we report the cloning and
      characterization of X. laevis Plx2 and Plx3, the likely homologs of mammalian
      Plk2 (Snk) and Plk3 (Fnk/Prk), respectively. RNA expression studies indicate that
      all three Xenopus Plks are present in both oocytes and unfertilized eggs. Further
      analysis by in situ hybridization revealed that Plx1 RNA is ubiquitously
      expressed in early embryos, but shows more restricted expression at later stages.
      In contrast, Plx2 and Plx3 expression is highly restricted in both early and late
      stage embryos. Using Plx-specific antisera, Plx1 and Plx3 polypeptides could
      readily be detected on immunoblots of oocyte and egg extracts. Both Plx1 and Plx3
      protein levels remained virtually constant during oocyte maturation. However,
      whereas Plx1 is more active in M phase than in I phase (P. Descombes and E. A.
      Nigg (1998) EMBO J. 17, 1328-1335), Plx3 protein and activity levels remained
      constant upon release of meiotic metaphase II-arrested egg extracts into
      interphase. Finally, microinjection of in vitro-transcribed RNAs for Plx1, Plx2,
      and Plx3 increased the rate of progesterone-induced oocyte maturation, and
      concomitantly, all three kinases became activated. Conversely, overexpression of
      the corresponding catalytically inactive kinases delayed maturation. This
      suggests that, at least in oocytes, all three kinases may be regulated by similar
      mechanisms, and they may also share common substrates. However, the strikingly
      restricted pattern of expression of Plx2 and Plx3 observed in embryos strongly
      suggests that individual Plk family members perform at least partly distinct
      functions at later stages of development.

PMID- 11597130
TI  - Methylation changes in the human IGF2 p3 promoter parallel IGF2 expression in the
      primary tumor, established cell line, and xenograft of a human hepatoblastoma.
AB  - Hepatoblastoma (HB) is a rare malignant embryonal liver tumor. Its pathogenesis
      has been associated with altered regulation of the IGF2 and H19 genes, and
      previous studies have suggested a correlation between abnormal methylation and
      altered expression of these genes in hepatoblastoma. Upregulation of the activity
      of the IGF2 promoter P3 has previously been shown to be tightly correlated with
      demethylation in hepatoblastoma. Here, we have used bisulfite genomic sequencing
      to characterize the methylation pattern of the IGF2 promoter P3 in the
      hepatoblastoma-derived cell line Hep T1, in the original tumor from which Hep T1
      is derived, and in nude mouse xenografts of the Hep T1 cell line. The results
      show a clear difference in methylation pattern of the most proximal region of the
      IGF2 P3 promoter between the primary tumor, the cell line, and the xenografts.
      RNase protection and mRNA in situ hybridization revealed that variations in
      methylation patterns was paralleled by the levels of IGF2 P3 mRNA, which was
      detectable in the primary tumor and xenografts, but not in the cell line.
      Furthermore, it was demonstrated that H19 was reactivated and demethylated in the
      HepT1 cell line by 5-azaCytidine, in contrast to IGF2 P3, which was not
      demethylated or reactivated. We suggest that methylation of the proximal IGF2 P3
      is important for its regulation.

PMID- 11597131
TI  - Nuclear assembly of demembranated Xenopus sperm in plant cell-free extracts from
      Nicotiana ovules.
AB  - The cell-free preparation derived from Nicotiana tabaccum ovules induced
      chromatin decondensation and pronuclear formation from demembranated Xenopus
      laevis sperm nuclei. Fluorescent microscope and phase-contrast microscope
      visualization of assembly intermediates indicated that 95.6% of X. leavis sperm
      changed their tadpole-like shape to circular shape or elliptical shape after over
      1.5 h of incubation. Transmission electron microscope visualization showed that
      nuclear membrane was assembled around the periphery of the dispersed chromatin.
      Nuclear envelope of most reassembled nuclei was composed of a double membrane
      inlaid with a little single membrane. Nucleosome assembly was verified by means
      of micrococcal nuclease digestion. After 2 to 5 h of incubation, digestion of the
      product of nuclear assembly with micrococcal nuclease produced at least six
      nucleosome fragments of about 250 bp each.

PMID- 11597132
TI  - DBD-fish on neutral comets: simultaneous analysis of DNA single- and double
      strand breaks in individual cells.
AB  - Humanblood leukocytes exposed to X-rays were immersed in an agarose microgel on a
      slide, extensively deproteinized, and electrophoresed under neutral conditions.
      Following this single-cell gel electrophoresis assay, characteristics of DNA
      migration (i.e., area of the comet) are related to the DNA double-strand breaks
      (dsbs) yield. After electrophoresis, comets were briefly incubated in an alkaline
      unwinding solution, transforming DNA breaks and alkali-labile sites into
      restricted single-stranded DNA (ssDNA) motifs. These motifs behave as target
      sites for hybridization with a whole genome probe, following the DNA breakage
      detection-fluorescence in situ hybridization (DBD-FISH) procedure. As DNA
      breakage increases with dose, more ssDNA is produced in the comet by the alkali
      and more DNA probe hybridizes, resulting in an increase in the mean fluorescence
      intensity. Since radiation-induced DNA single-strand breaks (ssbs) are far more
      frequent than dsbs, the mean fluorescence intensity of the DBD-FISH signal from
      the comet is related to the ssb level, whereas the surface area of the same comet
      signal is indicative of the dsb yield. Thus, both DNA break types may be
      simultaneously analyzed in the same cell. This was confirmed in a repair assay
      performing the DBD-FISH on neutral comets from a human cell line defective in the
      repair of dsbs. Otherwise, treatment with hydrogen peroxide, a main inducer of
      ssbs, increased the mean fluorescence intensity, but not the surface, of X-ray
      exposed human leukocytes.

PMID- 11597133
TI  - Cumulative influence of matrix metalloproteinase-1 and -2 in the migration of
      melanoma cells within three-dimensional type I collagen lattices.
AB  - During melanoma progression, migrating cells must cross human dermis, a type I
      collagen-rich tissue. We have show that MMP-1 and MMP-2 act in a cumulative
      manner in the in vitro invasion of a three-dimensional type I collagen matrix by
      melanoma cells. Two melanoma cell lines (M1Dor and M3Da) previously reported to
      secrete proMMP-2 in a direct relationship with their tumorigenic potential into
      nude mice were used (F. Capon et al., 1999, Clin. Exp. Metastasis 17, 463-469).
      The highly tumorigenic cell line (M3Da) displayed a five-fold faster migration
      rate in type I collagen matrix, compared to its lower tumorigenic counterpart
      (M1Dor). In parallel, activation of proMMP-2 was evidenced in M3Da- but not M1Dor
      populated collagen lattices. Such enzyme activation was associated with a
      significant decrease in TIMP-2 and TIMP-1 production. Agents known to interfere
      with proMMP-2 activation, i.e., excess TIMP-2, furin convertase inhibitor, and
      alphavbeta3 blocking antibody, reduced by 30-40% the type I collagen invasive
      capacity of M3Da cells. By comparison, batimastat, a wide-spectrum MMP inhibitor,
      exhibited a more pronounced inhibitory effect (>70%). It suggested that other
      collagenases than MMP-2 could participate in type I collagen invasion.
      Collagenase-3 (MMP-13) was produced at low levels by melanoma cells whatever the
      cell culture conditions. In contrast, M3Da and M1Dor cells secreted collagenase-1
      (MMP-1) following 48 h of culture on plastic dishes. Growing melanoma cells in
      type I collagen gel did not modify enzyme production, but induced proMMP-1
      activation in M3Da but not M1Dor cell-populated lattices. Blocking the plasmin
      mediated proMMP-1 activation by aprotinin inhibited type I collagen gel invasion
      by 30%. Since the combination of aprotinin and furin convertase inhibitor reduced
      collagen invasiveness by melanoma cells to a level comparable to that attained
      with batimastat, we conclude that both MMP-2 and MMP-1 are involved in such
      tissue invasion.

PMID- 11597134
TI  - Evading apoptosis by calcitriol-differentiated human leukemic HL-60 cells is not
      mediated by changes in CD95 receptor system but by increased sensitivity of these
      cells to insulin.
AB  - Previous studies revealed that 1,25-dihydroxyvitamin D(3) (calcitriol)-induced
      differentiation of human promyelocytic leukemia cells leads to an increased
      resistance of the cells to apoptosis-inducing agents. However many attempts were
      made to explain it, the mechanism underlying this effect still remains unclear.
      Our results suggest that the acquired resistance to apoptosis-inducing agents in
      HL-60 cells is not mediated by the CD95 receptor/ligand system. The expression of
      CD95 on the surface of HL-60 cells is very low and does not change during the
      calcitriol-induced differentiation of HL-60 cells. Studies presented here provide
      a strong indication that this receptor is unable to transmit the death signal in
      either differentiated or undifferentiated HL-60 cells. We therefore asked if
      evading apoptosis by differentiated human leukemia HL-60 cells may be caused by
      their increased sensitivity to growth factors contained in fetal calf serum. This
      study demonstrates that HL-60 promyelocytic leukemia cells, differentiated by
      exposure to calcitriol, undergo apoptosis in serum-free conditions. As low as 1%
      of fetal calf serum is enough to prevent cell death of differentiated HL-60
      cells. The ability of 1% fetal calf serum to prevent apoptosis can be blocked by
      the specific inhibitor of phosphatidylinositol 3-kinase, LY294002. We then tried
      to find out which component of fetal calf serum may be able to prevent serum-free
      cell death of differentiated cells. It appeared that serum-free cell death of
      differentiated HL-60 cells is reversed by addition of 10 microM insulin to the
      culture medium. The antiapoptotic activity of insulin can be inhibited by
      LY294002. Moreover, insulin increases the viability of differentiated, but not of
      undifferentiated, HL-60 cells.

PMID- 11597135
TI  - The mouse genome sequence: status and prospects.

PMID- 11597136
TI  - Phylogenetic conservation of the makorin-2 gene, encoding a multiple zinc-finger
      protein, antisense to the RAF1 proto-oncogene.
AB  - Natural endogenous antisense RNAs have been reported in multiple loci, with
      evidence in some cases supporting a regulatory role for the antisense transcript.
      Here, we describe a novel gene, makorin RING zinc finger-2 (MKRN2), that overlaps
      and is antisense to the gene RAF1 in mammals. Phylogenetic analysis of the 3'
      untranslated region of RAF1 orthologues suggests that this relationship may have
      existed for up to 450 million years. We have also identified MKRN2 orthologues in
      two species of fish. This places the gene duplication event that created this
      locus from an ancestral MKRN1 gene early in vertebrate evolution, over 450
      million years ago. Northern blot analyses show that human MKRN2 and RAF1 are co
      expressed in tissues and cell lines, raising the possibility of mRNA duplex
      formation. The encoded makorin-2 protein is likely a ribonucleoprotein of unknown
      function, but its conservation suggests an important cellular role. The data
      presented here describe a conserved vertebrate MKRN2 gene that is closely
      associated with the RAF1 locus.

PMID- 11597137
TI  - Skipping of exon 9 of human CFTR in YAC-transgenic mice.
AB  - Exon 9 of the human gene CFTR is skipped in some mRNA transcripts in human
      tissues. The level of skipping correlates with the number of TG's and T's in the
      5' splice acceptor of exon 9. Poorly spliced alleles are associated with mild
      cystic fibrosis related phenotypes. Here we describe transgenic mice carrying a
      yeast artificial chromosome (YAC) with the intact human gene CFTR. When the YAC
      carries 10 TG's and 7 T's at the splice acceptor, there is about 50% skipping of
      exon 9 in most tissues, whereas 12 TG's and 5 T's give about 90% skipping. The
      level of skipping is quite uniform over many tissues, except the testis, in which
      there is a much higher level of correct splicing. These mice confirm that the
      TG(m)T(n) polymorphism has an effect on splicing and should be valuable for
      studying this phenomenon.

PMID- 11597138
TI  - An 800-kb region of deletion at 13q14 in human prostate and other carcinomas.
AB  - Deletions of regions at 13q14 have been detected by various genetic approaches in
      human cancers including prostate cancer. Several studies have defined one region
      of loss of heterozygosity (LOH) at 13q14 that seems to reside in a DNA segment of
      7.1 cM between genetic markers D13S263 and D13S153. To define the smallest region
      of overlap (SRO) for deletion at 13q14, we first applied tissue microdissection
      and multiplex PCR to detect homozygous deletion and/or hemizygous deletion at
      13q14 in 134 prostate cancer specimens from 114 patients. We detected deletions
      at markers D13S1227, D13S1272, and A005O48 in 13 (10%) of these tumor specimens.
      Of the 13 tumors with deletions, 12 were either poorly differentiated primary
      tumors or metastases of prostate cancer. To fine-map the deletion region, we then
      constructed a high-resolution YAC/BAC/STS/EST physical map based on experimental
      and database analyses. Several markers encompassing the deletion region were
      analyzed for homozygous deletion and/or hemizygous deletion in 61 cell
      lines/xenografts derived from human cancers of the prostate, breast, ovary,
      endometrium, cervix, and bladder, and a region of deletion was defined by duplex
      PCR assay between markers A005X38 and WI-7773. We also analyzed LOH at 13q14 in
      the 61 cell lines/xenografts using the homozygosity mapping of deletion approach
      and 26 microsatellite markers. We found 24 (39%) of the cell lines/xenografts to
      show LOH at 13q14 and defined a region of LOH by markers M1 and M5. Combination
      of homozygous or hemizygous deletion and LOH results defined the SRO for deletion
      to be an 800-kb DNA interval between A005X38 and M5. There are six known genes
      located in or close to the SRO for deletion. This region of deletion is at least
      2 Mb centromeric to the RB1 tumor-suppressor gene and the leukemia-associated
      genes 1 and 2, each of which is located at 13q14. These data suggest that the 800
      kb DNA segment with deletion contains a gene whose deletion may be important for
      the development of prostate and other cancers. This study also provides a
      framework for the fine-mapping, cloning, and identification of a novel tumor
      suppressor gene at 13q14.

PMID- 11597139
TI  - Comparative genomic analysis of genes encoding translation elongation factor
      1B(alpha) in human and mouse shows EEF1B1 to be a recent retrotransposition
      event.
AB  - We have characterized genomic loci encoding translation elongation factor
      1B(alpha) (eEF1B(alpha)) in mice and humans. Mice have a single structural locus
      (named Eef1b2) spanning six exons, which is ubiquitously expressed and maps close
      to Casp8 on mouse chromosome 1, and a processed pseudogene. Humans have a single
      intron-containing locus, EEF1B2, which maps to 2q33, and an intronless paralogue
      expressed only in brain and muscle (EEF1B3). Another locus described previously,
      EEF1B1, is actually a processed pseudogene on chromosome 15 corresponding to an
      alternative splice form of EEF1B2. Our study illustrates the value of comparative
      mapping in distinguishing between processed pseudogenes and intronless
      paralogues.

PMID- 11597140
TI  - The pattern of gene expression in mouse Gr-1(+) myeloid progenitor cells.
AB  - To understand the pattern of gene expression in mouse myeloid progenitor cells,
      we carried out a genome-wide analysis of gene expression in mouse bone marrow Gr
      1(+) cells using SAGE and GLGI techniques. We identified 22,033 unique SAGE tags
      with quantitative information from 73,869 collected SAGE tags. Among these unique
      tags, 64% match known sequences, including many genes important for myeloid
      differentiation, and 36% have no matches to known sequences and are likely to
      represent novel genes. We compared the expression of mouse Gr-1(+) and human
      CD15(+) myeloid progenitor cells and showed that the pattern of gene expression
      of these two cell populations had some similarities. We also compared the
      expression of mouse Gr-1(+) myeloid progenitor cells with that of mouse brain
      tissue and found a highly tissue-specific manner of gene expression in these two
      samples. Our data provide a basis for studying altered gene expression in myeloid
      disorders using mouse models.

PMID- 11597141
TI  - Cloning and chromosomal localization of a gene encoding a novel serine/threonine
      kinase belonging to the subfamily of testis-specific kinases.
AB  - Using reverse transcription-polymerase chain reaction (RT-PCR) with degenerate
      oligonucleotides corresponding to two highly conserved motifs within the protein
      kinase family of catalytic domains, we isolated a PCR fragment encoding a novel
      member of the testis-specific serine/threonine kinases (STK) from mouse male
      mixed germ cell mRNA. This PCR fragment recognized a 1020-bp transcript in male
      germ cells by northern blot analysis and was used to clone a full-length cDNA
      from a mouse mixed germ cell cDNA library. This cDNA has an open reading frame of
      804 bases encoding a protein of 268 amino acids. This novel gene is almost
      identical to Stk22c, encoding a recently described testis-specific protein
      kinase, except for base-pair deletions that result in a shift in the coding
      region and an alteration of 22 amino acids (residues 109-131). Due to its
      homology with Stk22c, we have called this protein kinase gene Stk22d. Northern
      blot analysis revealed that this protein kinase is developmentally expressed in
      testicular germ cells and is not present in brain, ovary, kidney, liver, or early
      embryonic cells. We then cloned the human homologue of this protein kinase gene
      (STK22C) and found it to be expressed exclusively in the testis. Fluorescence in
      situ hybridization with both the human and mouse cDNA clones revealed syntenic
      localization on chromosomes 1p34-p35 and 4E1, respectively.

PMID- 11597142
TI  - Candidate gene isolation and comparative analysis of a commonly deleted segment
      of 7q22 implicated in myeloid malignancies.
AB  - Monosomy 7 and deletion of 7q are recurring abnormalities in malignant myeloid
      diseases. Here we extensively characterize an approximately 2-Mb commonly deleted
      segment (CDS) of 7q22 bounded by D7S1503 and D7S1841. Approximately 1.8 Mb of
      sequence have been generated from this interval, facilitating the construction of
      a transcript map that includes large numbers of genes and ESTs. The intron/exon
      organization of seven genes and expression patterns of three genes were
      determined, and leukemia samples were screened for mutations in five genes. We
      have used polymorphic markers from this region to examine leukemia cells for
      allelic loss within 7q22. Finally, we isolated mouse genomic clones orthologous
      to several of the characterized human genes. Fluorescence in situ hybridization
      studies using these clones indicate that a region of orthologous synteny lies on
      proximal mouse chromosome 5. These resources should greatly accelerate the pace
      of candidate gene discovery in this region.

PMID- 11597143
TI  - Genomic organization of the X-linked inhibitor of apoptosis and identification of
      a novel testis-specific transcript.
AB  - Here we report the genomic organization and mapping of the X-linked inhibitor of
      apoptosis gene (BIRC4, also known as XIAP and hILP) and the identification of a
      closely related transcript. BIRC4 is located on Xq25 and is composed of seven
      exons. The intron/exon structure is highly conserved between the mouse homologue
      and its human counterpart. Four bands cross-react with a BIRC4 coding region
      probe on a genomic Southern blot. One of these cross-reactive bands encodes an
      intronless gene that expresses a 2.2-kb transcript solely in the testis. This
      testis-specific transcript contains a putative open reading frame (ORF) that is
      homologous to the carboxy-terminal end of BIRC4; overexpression of this ORF shows
      protective effects against BAX-induced apoptosis.

PMID- 11597144
TI  - Physical mapping of the mouse tilted locus identifies an association between
      human deafness loci DFNA6/14 and vestibular system development.
AB  - The tilted (tlt) mouse carries a recessive mutation causing vestibular
      dysfunction. The defect in tlt homozygous mice is limited to the utricle and
      saccule of the inner ear, which completely lack otoconia. Genetic mapping of tlt
      placed it in a region orthologous with human 4p16.3-p15 that contains two loci,
      DFNA6 and DFNA14, responsible for autosomal dominant, nonsyndromic hereditary
      hearing impairment. To identify a possible relationship between tlt in mice and
      DFNA6 and DFNA14 in humans, we have refined the mouse genetic map, assembled a
      BAC contig spanning the tlt locus, and developed a comprehensive comparative map
      between mouse and human. We have determined the position of tlt relative to 17
      mouse chromosome 5 genes with orthologous loci in the human 4p16.3-p15 region.
      This analysis identified an inversion between the mouse and human genomes that
      places tlt and DFNA6/14 in close proximity.

PMID- 11597145
TI  - TTYH2, a human homologue of the Drosophila melanogaster gene tweety, is located
      on 17q24 and upregulated in renal cell carcinoma.
AB  - Using differential display PCR, we identified a novel gene upregulated in renal
      cell carcinoma. Characterization of the full-length cDNA and gene revealed that
      the encoded protein is a human homologue of the Drosophila melanogaster Tweety
      protein, and so we have termed the novel protein TTYH2. The orthologous mouse
      cDNA was also identified and the predicted mouse protein is 81% identical to the
      human protein. The encoded human TTYH2 protein is 534 amino acids and, like the
      other members of the tweety-related protein family, is a putative cell surface
      protein with five transmembrane regions. TTYH2 is located at 17q24; it is
      expressed most highly in brain and testis and at lower levels in heart, ovary,
      spleen, and peripheral blood leukocytes. Expression of this gene is upregulated
      in 13 of 16 (81%) renal cell carcinoma samples examined. In addition to a
      putative role in brain and testis, the over-expression of TTYH2 in renal cell
      carcinoma suggests that it may have an important role in kidney tumorigenesis.

PMID- 11597146
TI  - Documentation of positive blood culture results in a London teaching hospital.
AB  - OBJECTIVES: Our current practice is that initial (day 1) positive blood culture
      results are communicated to clinical teams; the task of recording those results
      in the notes is left to the clinical team. Microbiological information may be of
      crucial importance to an on-call doctor asked to review an unwell patient. We
      therefore sought to establish the extent to which day 1 positive blood culture
      information is available in patients' notes and its accuracy. METHODS: There were
      51 positive blood cultures over a 14-day period. Patient notes of 39 of these
      were available for examination for evidence of the day 1 culture report, the
      accuracy of that report and evidence of clinical interpretation. RESULTS: The
      proportion of notes with a record was disappointingly low (54%), although the
      record was almost always accurate. Results reported at the weekend were as likely
      to be recorded in the notes as those given during the week. CONCLUSION: On-call
      doctors, not previously acquainted with a patient, will find that important
      information about day 1 positive blood culture results is not available to them
      in patient notes in around half of all cases. This adds weight to the view that
      medical microbiologists should give greater priority to ward visits and
      documentation of significant results, thus ensuring continuity of care from the
      laboratory bench to the bedside.

PMID- 11597147
TI  - Severe Pneumocystis carinii pneumonia increases the infectious titre of HIV-1 in
      blood and can promote the expansion of viral chemokine co-receptor tropism.
AB  - AIM: Determine the in vivo effect of Pneumocystis carinii pneumonia (PCP) on: (a)
      the titre of infectious virus circulating in blood; and (b) the chemokine co
      receptor usage of these viruses. PATIENTS AND METHODS: A longitudinal study of 62
      patients over 8 years. The results for PCP were compared with those for
      disseminated cytomegalovirus (CMV) and acute herpes simplex virus type 1
      infections (HSV). Blood was collected every 3-4 months when patients were well,
      and again when they were acutely ill. A tissue culture based PHA/IL-2 induced HIV
      replication assay was used to determine the frequency of circulating cells in
      blood carrying infectious forms of HIV-1. Viral isolates were phenotyped using
      U87 cells transfected with CD4 and a chemokine co-receptor. RESULTS: There were
      29 cases of PCP, 18 cases of HSV and 11 cases of CMV. A significant increase in
      the viral replication assay was seen during severe PCP but not during HSV or CMV
      infections. The number of chemokine co-receptors being used by HIV-1 increased
      during severe PCP to include CXCR4 and CCR3 in three of six patients from whom
      viruses were available for detailed study. CONCLUSIONS: Severe PCP can increase
      the number of PBMN cells containing integrated, replication competent, infectious
      forms of HIV-1 circulating in blood. The expanded chemokine co-receptor tropism
      of these viral isolates could promote the dissemination of HIV-1 from lymphoid to
      non-lymphoid organs and explain the poor prognosis of patients who develop severe
      PCP.

PMID- 11597148
TI  - Conjunctivitis due to Chlamydophila felis (Chlamydia psittaci feline pneumonitis
      agent) acquired from a cat: case report with molecular characterization of
      isolates from the patient and cat.
AB  - Conjunctivitis due to Chlamydiaceae other than Chlamydia trachomatis is rarely
      reported because of infrequent occurrence or inadequate investigation. A case of
      chronic non-trachomatis chlamydial conjunctivitis is described. After full
      clinical information was supplied to the laboratory, a non-trachomatis chlamydia
      was recovered from the patient's eye. This organism, and a subsequent isolate
      from one of the patient's cats, were shown to be indistinguishable examples of
      the recently described species Chlamydophila felis. The infection was most likely
      acquired from the patient's cats. A prolonged course of doxycycline was required
      to eradicate the infection.

PMID- 11597149
TI  - Seroconversion to HIV-1 following a needlestick injury despite combination post
      exposure prophylaxis.
AB  - Post-exposure prophylaxis with antiretroviral drugs for at-risk needlestick
      injuries has become routine practice and is usually empirical. With increasing
      numbers of treatment-experienced patients, the choice of antiretroviral may need
      to be individually tailored. Infection can still occur despite attempts to
      optimize the drug combination used.

PMID- 11597150
TI  - Pulmonary infection with Scedosporium prolificans in an immunocompetent
      individual.
AB  - We report a case of histologically confirmed Scedosporium prolificans pulmonary
      infection secondary to long-standing bronchiectasis that necessitated excision
      lung surgery. This case emphasizes the difficulties with the medical management
      of deep-seated fungal infections.

PMID- 11597151
TI  - Post-coronary artery bypass surgery pericardial abscess: Salmonella paratyphi B.
AB  - Endemic enteric fever is one of the major health problems in South Asia where
      focal pyogenic infections with salmonella are being increasingly reported. A
      pericardial abscess following coronary artery bypass surgery with Salmonella
      paratyphi B was successfully treated, the first reported case so far.

PMID- 11597152
TI  - A case of Salmonella paratyphi B septicaemia complicated by disseminated
      intravascular coagulation, severe hepatitis rhabdomyolysis and acute renal
      failure.

PMID- 11597153
TI  - Preventing infectious intestinal disease in the domestic setting: a shared
      responsibility. Proceedings of a conference. December 6-7, 2000. London, United
      Kingdom.

PMID- 11597154
TI  - Gastrointestinal disease in the domestic setting: what are the issues?

PMID- 11597155
TI  - Gastrointestinal disease in the domestic setting: what can we deduce from
      surveillance data?

PMID- 11597156
TI  - Gastrointestinal disease in the domestic setting: what can we deduce from
      surveillance data?

PMID- 11597157
TI  - The role of viruses in gastrointestinal disease in the home.

PMID- 11597158
TI  - The role of viruses in gastrointestinal disease in the home.

PMID- 11597159
TI  - Developing a rational approach to hygiene in the domestic setting.

PMID- 11597160
TI  - The spread and persistence of Campylobacter and Salmonella in the domestic
      kitchen.

PMID- 11597161
TI  - Escherichia coli O157:H7: lessons for the domestic setting.

PMID- 11597162
TI  - Protecting vulnerable groups in the home: the interface between institutions and
      the domestic setting.

PMID- 11597163
TI  - Hygiene and the immune system.

PMID- 11597164
TI  - Hygiene and the immune system.

PMID- 11597165
TI  - Evaluating hygiene behaviour in the domestic setting and the impact of hygiene
      education.

PMID- 11597166
TI  - Hygiene: how myths, monsters, and mothers-in-law can promote behaviour change.

PMID- 11597167
TI  - WHO surveillance programme for control of foodborne infections and intoxications:
      preliminary results and trends across greater Europe. World Health Organization.

PMID- 11597168
TI  - Biocide usage in the domestic setting and concern about antibacterial and
      antibiotic resistance.

PMID- 11597169
TI  - Application of quantitative risk assessment for formulating hygiene policy in the
      domestic setting.

PMID- 11597170
TI  - The impact of changing sustainable technology and changing consumer habits on
      infectious disease transmission in the domestic setting.

PMID- 11597171
TI  - Regulation of the nitric oxide production resulting from the glucocorticoid
      insensitive expression of iNOS in human osteoarthritic cartilage.
AB  - OBJECTIVE: Nitric oxide (NO) produced by cartilage and synovial membranes is
      implicated in the pathogenesis of osteoarthritis (OA) and inhibitors of NO
      synthesis may have indications in the treatment or prevention of joint
      destruction in OA. Because the signaling mechanisms as well as the NOS isoform
      involved in induction of NO production in human cartilage remain in many parts
      unclear, the present study was designed to investigate the regulation of
      inducible NO synthesis in human intact OA cartilage. METHODS: Cartilage specimens
      were collected from OA patients undergoing knee replacement surgery and studied
      for iNOS expression and NO production in organ culture to allow intact
      chondrocyte-matrix interactions. J774 macrophages were used for comparison as a
      well-documented source of iNOS. RESULTS: OA cartilage expressed iNOS and produced
      NO in the absence of exogenous cytokines. Addition of interleukin-1 beta (IL-1
      beta), tumor necrosis factor alpha (TNF alpha) or lipopolysaccharide (LPS) into
      the culture medium enhanced NO production in a dose-and time-dependent manner.
      Various NOS inhibitors suppressed NO production in the following order of
      potency: 1400W (novel selective iNOS inhibitor)=L-NIO>L-NMMA>L-NAME.
      Cycloheximide (an inhibitor of protein synthesis), pyrrolidine dithiocarbamate
      (PDTC; an NF-kappa B inhibitor) and genistein (an inhibitor of tyrosine protein
      kinases) inhibited cytokine-induced NO production, while dexamethasone,
      diaminohydroxypyrimidine (DAHP; an inhibitor of tetrahydrobiopterin synthesis)
      and PD 98059 (p42/44 MAP kinase inhibitor) had no effect. CONCLUSIONS: The
      results suggest that NO synthesis in human osteoarthritic cartilage derives from
      the glucocorticoid-insensitive expression of iNOS. Very similar mechanisms appear
      to regulate inducible NO synthesis in human osteoarthritic cartilage and J774
      macrophages with the exception that dexamethasone inhibited NO production in J774
      cells but not in osteoarthritic cartilage.

PMID- 11597172
TI  - A cross-sectional study of the association between Heberden's nodes, radiographic
      osteoarthritis of the hands, grip strength, disability and pain.
AB  - OBJECTIVE: To describe the associations between hand osteoarthritis (OA), pain
      and disability in males and females and to further validate the
      Australian/Canadian OA hand index (AUSCAN LK3.0). DESIGN: Cross-sectional study
      of 522 subjects from 101 Tasmanian families (males N=174, females N=348). Hand OA
      was assessed by two observers using the Altman atlas for joint space narrowing
      and osteophytes at distal interphalangeal and first carpometacarpal joints as
      well as a score for Heberden's nodes based on hand photography. Hand pain and
      function were assessed by the AUSCAN LK3.0 and grip strength by dynamometry in
      both hands on two occasions. RESULTS: The prevalence of hand OA was high in this
      sample at 44-71% (depending on site). Pain and dysfunction increased with age
      while grip strength decreased (all P< 0.001). All three measures were markedly
      worse in women, even after taking the severity of arthritis into account. Hand OA
      explained 5.7-10% of the variation in function, grip strength and pain scores,
      even after adjustment for age and sex. Further adjustment suggested that the
      osteoarthritic associations with function and grip strength were largely mediated
      by pain. Severity of disease was more strongly associated with these scores than
      presence or absence. Lastly, the AUSCAN LK3.0 showed a comparable association to
      grip strength with structural damage providing further evidence of index
      validity. CONCLUSIONS: Hand OA at these two sites makes substantial contributions
      to hand function, strength and pain. The associations with function and strength
      measures appear mediated by pain. Gender differences in all three measures
      persist after adjustment for variation in age and OA severity indicating that
      factors apart from radiographic disease are responsible.

PMID- 11597173
TI  - Serum cartilage oligomeric matrix protein reflects the presence of clinically
      diagnosed synovitis in patients with knee osteoarthritis.
AB  - OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a component of articular
      cartilage whose serum levels show a strong correlation with radiographic
      osteoarthritis (OA) status. It has recently been found, however, that COMP is
      also produced in synovium. To assess the hypothesis that synovitis affects serum
      COMP levels in patients with knee OA, we collected sera for COMP simultaneous
      with a clinical examination for synovitis. DESIGN: Sera were collected from OA
      patients who fulfilled the American College of Rheumatology criteria for knee OA.
      Radiographs were classified according to the grading system of Kellgren and
      Lawrence. Synovitis was diagnosed clinically by joint tenderness plus swelling
      and/or increased warmth over the joint. COMP levels in sera were measured by
      inhibition ELISA with monoclonal antibody (mAb) 17-C10. RESULTS: Serum COMP
      levels were significantly correlated with age, synovitis and an interaction of
      synovitis and OA severity. Synovitis showed the strongest effect on COMP levels
      (R=0.1587, P< 0.01), in contrast to C-reactive protein, duration of OA and OA
      severity score which showed no significant effect on COMP levels. Individual
      signs of synovitis, namely, joint tenderness and warmth had a significant effect
      on serum COMP levels while swelling alone did not. CONCLUSION: Synovitis exerts a
      significant effect on serum COMP levels measured with mAb 17-C10 in OA patients.
      These findings underscore the importance of the clinical joint examination to
      assess for synovitis, when attempting to apply objective measures, such as COMP,
      to the clinical setting.

PMID- 11597174
TI  - Modulation of the inflammatory response in the rat TMJ with increasing doses of
      complete Freund's adjuvant.
AB  - OBJECTIVES: Acute inflammation stresses the physiological system, which must
      respond in order to reestablish homeostasis. The purpose of this study was to
      determine whether bilateral temporomandibular joint (TMJ) injections of different
      doses of Complete Freund's Adjuvant (CFA) produced dose-dependent changes in
      biologic markers of acute inflammation. The ability to establish an animal model
      with varying degrees of joint inflammation would allow evaluation of agents or
      conditions that could modulate the severity of the disease. DESIGN: The TMJs of
      three groups of male Sprague-Dawley rats were injected with CFA containing
      varying doses of Mycobacterium tuberculosis (MT). A group of non-injected and a
      group of saline injected rats were used as controls. Food intake, body weights,
      swelling and chromodacryorrhea were recorded daily. Interleukin-1 beta (IL-1
      beta) and corticosterone levels were assayed and condylar cartilage thickness was
      measured 48 h after injections. RESULTS: Twenty-four hours post-injection,
      bilateral TMJ swelling and chromodacryorrhea were significantly (P< 0.05)
      increased following 10 microg of MT and further increased with elevated MT dose.
      In the CFA groups food intake was attenuated (P< 0.01) 24 and 48 h post-injection
      and negatively correlated with dose at 24 h. Body weight was also negatively
      correlated with dose. TMJ retrodiscal tissues IL-1 beta was increased (P< 0.05)
      in a dose-dependent manner. CFA increased corticosterone (P< 0.05), but this
      elevation was not dose dependent. Condylar cartilage thickness was decreased in a
      dose-dependent manner. CONCLUSIONS: These data suggest that an intermediate dose
      of CFA can be used to effect submaximal levels of TMJ inflammation that will
      allow experimental modulation in future studies.

PMID- 11597175
TI  - Biochemical composition of equine carpal articular cartilage is influenced by
      short-term exercise in a site-specific manner.
AB  - It was hypothesized that cartilage macro-molecular characteristics are influenced
      by exercise intensity and by location within a joint. OBJECTIVE: To determine the
      macromolecular characteristics of carpal articular cartilage at common and
      uncommon sites of pathology in horses undergoing high or low intensity exercise,
      and to compare this composition between exercise groups. DESIGN: Twelve horses
      (19.3+/-0.9 years) were assigned to exercise groups. Each group underwent 19
      weeks high-intensity treadmill training (N=6) or low-intensity exercise (N=6).
      Dorsal and palmar test sites were identified on radial, intermediate and third
      carpal articular surfaces after euthanasia. Cartilage was collected from each
      site, freeze-dried and assessed for water content. Hydroxyproline,
      glycosaminoglycan and DNA analyses were performed on cartilage from each test
      site. Adjacent cartilage underwent histological preparation and assessment for
      chondrocyte numerical density at each site and proteoglycan distribution through
      the depth of cartilage. RESULTS: Dorsal cartilage had a higher collagen content,
      DNA content, and chondrocyte numerical density, but lower glycosaminoglycan
      content than palmar cartilage. Cartilage from horses undergoing high-intensity
      training had a significantly higher glycosaminoglycan content than cartilage from
      horses undergoing low-intensity exercise, with maximal difference being observed
      in cartilage from dorsal radial and dorsal intermediate carpal articular
      surfaces. Overall no effect of exercise on collagen was observed, but at sites
      predisposed to clinical lesions cartilage from horses undergoing high-intensity
      training contained significantly less collagen than from horses undergoing low
      intensity exercise. Distribution of proteoglycan was non-uniform in 52% of the
      sections examined, with superficial loss of toluidine blue staining primarily at
      dorsal sites and in the high-intensity exercise group. CONCLUSIONS: These results
      indicate that topographical and exercise related differences exist in carpal
      cartilage composition, and that the effect of exercise on overall composition and
      distribution within the cartilage was maximal at sites predisposed to clinical
      lesions. These findings could indicate that the combined effect of exercise and
      local load variations within a joint may lead to a risk of exceeding the
      physiologic threshold at high load sites that are predisposed to clinical injury.

PMID- 11597176
TI  - Altered mechanics and histomorphometry of canine tibial cartilage following joint
      immobilization.
AB  - Joint immobilization is associated with altered cartilage biosynthesis and
      catabolism that may affect cartilage mechanics and joint function. In this study,
      the mechanical behavior of articular cartilage was studied in an experimental
      model of joint immobilization, in which the canine knee was cast-immobilized at
      90 degrees of flexion for 4 weeks. Articular cartilage from the medial tibial
      plateau was tested in compression and in shear. Biochemical assays for water and
      glycosaminoglycan content and histomorphometric grading were performed on site
      matched samples. Significant decreases in the equilibrium and dynamic shear
      moduli, but not compressive moduli, were observed in cartilage after 4 weeks of
      joint immobilization as compared to cartilage from a separate control population.
      Importantly, there was also evidence of a decrease in the compressive and shear
      moduli of tibial cartilage from the contralateral knee joints compared to control
      joints that were not immobilized. No significant effect of immobilization on the
      biochemical parameters or histomorphometric scores was detected, expect for a
      significant loss of proteoglycan staining following immobilization. These
      findings for changes in the tibial cartilage following cast immobilization are
      consistent with a mild form of cartilage degeneration.

PMID- 11597178
TI  - The small proteoglycans decorin and biglycan in human articular cartilage of late
      stage osteoarthritis.
AB  - OBJECTIVE: Disturbances in proteoglycan metabolism of hyaline cartilage play an
      essential role in the pathology of degenerative joint disease. We investigated
      the relation between transcript expression, protein synthesis and the
      ultrastructural localization of the matrix-organizing proteoglycans decorin and
      biglycan within intra- and extracellular compartments of late-stage
      osteoarthritic human articular cartilage. METHODS: Human cartilage samples of a
      macroscopically intact area, the adjoining area and an area of the main defect
      from knee joints of 10 patients with late stage osteoarthritis were investigated.
      In situ hybridization and immunogold histochemistry were carried out separately
      and in combination at the light and electron microscopic level. RESULTS:
      Ultrastructurally, three main chondrocyte types were identified. The highest
      levels of mRNA of decorin and biglycan were produced by elongated secretory type
      2 cells, already known to synthesize type I collagen. Cells with high levels of
      mRNA also translated the corresponding proteins to be found in the extracellular
      compartment. The highest production rate of decorin and biglycan was seen in the
      tissue area adjoining the main defect. CONCLUSION: The results indicate that at
      late stages of osteoarthritis the levels of transcription and translation for
      decorin and biglycan are up-regulated, probably in an effort to compensate for
      the general proteoglycan loss, characteristic of this disease stage.

PMID- 11597179
TI  - DNA cytofluorometric analysis of chondrocytes in human articular cartilages under
      normal aging or arthritic conditions.
AB  - OBJECTIVE: Since most chondrocytes in articular cartilage are in the resting
      phase (G0) of the cell cycle, it has been difficult to investigate their cell
      kinetics using 3H-thymidine autoradiography, or immunohistochemistry. In the
      present study, DNA cytofluorometry, which is useful to analyse the cell kinetics
      even for such inactive cell populations as in the G0 phase, was applied to human
      chondrocytes of the articular cartilages under normal aging and pathologic
      conditions such as osteoarthritis (OA), rheumatoid arthritis (RA), and aseptic
      necrosis (AN). DESIGN: The human articular cartilages for the study were obtained
      from autopsy and surgical materials. Fifty joints were used for the study of
      aging, 54 for the study of OA, 20 for studying RA, and 10 for AN study. The
      isolated chondrocytes were quickly prepared from fresh articular cartilages,
      using a combination method of enzymatic digestion with papain and collagenase,
      followed by mechanical cell separation by churning and homogenization. RESULTS:
      The DNA histograms obtained by cytofluorometry with propidium-iodide staining
      showed that most chondrocytes had diploid DNA content (2c) in all cartilages
      studied, suggesting that they were in the G0 phase. However, there were a few
      chondrocytes having tetraploid DNA content (4c) in the normally aged articular
      cartilages, and there were some cells having DNA content between 2c and 4c in the
      diseased cartilages. The former cells were considered to be G0-phase cells of the
      4c chondrocytes, while the latter cells were considered to be in the DNA
      synthetic (S) phase or G2-phase of the 2c chondrocytes. The frequency of 4c
      chondrocytes in aged cartilage was significantly increased, compared to that in
      the young cartilage. In contrast to the normal cartilage, the frequency of S- and
      G2-phase cells, which was expressed as the S- G2 index, in diseased cartilages
      (OA, RA and AN) was significantly high (P< 0.0001). In OA cartilage, the S-G2
      index was much higher in the severe or moderate stage than in the mild stage,
      suggesting that the chondrocytes in clusters may actively proliferate.
      CONCLUSION: These results showed that in normal articular cartilages most
      chondrocytes are in the G0 phase, while some became 4c polyploid cells, and that
      these G0-phase chondrocytes had a potential to proliferate under diseased
      conditions.

PMID- 11597180
TI  - A biokinetic model to describe consequences of inhibition/stimulation in DNA
      proofreading and repair-1. Development of the model.
AB  - A biokinetic model is described which deals with the mathematical consequences of
      the inhibition or stimulation of DNA proofreading. It demonstrates the
      development of the number of DNA mismatch-dependent cells (e.g. cells with a
      malignant phenotype), where such mismatches arise by the in situ interaction of
      various substances with nucleotides of the DNA. The model can test for
      consequences by a logic gating on an "if-then" type of analysis in relation to
      the separate and consecutive processes of proofreading and repair. In particular,
      the consequences are considered in cases where either (i) the efficacy of
      proofreading and repair are reduced/prevented (inhibited) or (ii) are increased
      by some form of stimulation. On the chosen kinetic parameters, the model is
      accessible to manipulation as new data arising from further investigations become
      available and are introduced. The model is based on recently published data which
      show that an increased "mutant fraction" (see note on terms) arises in DNA
      replication when intracellular nucleotide pools show "asymmetries" (see note on
      terms). Extraordinarily high mutant fractions can be predicted/have been recorded
      in the presence of proofreading inhibitors. The model expresses data in
      mathematical terms of the competition between the development of mismatch
      dependent cells and those with authentic genetic information. (Feedback and
      metastasis-effects and those of wild-type replicates are included.) A
      computerized (numerical) integration of the corresponding set of differential
      equations is offered. (A diskette with the program CANCER.xls is available upon
      request.)

PMID- 11597181
TI  - Self-deception in an evolutionary game.
AB  - From the perspective of philosophy, the idea of humans lying to themselves seems
      irrational and maladaptive, if even possible. However, the paradigm of cognitive
      modularity admits the possibility of self-deception. Trivers argues that self
      deception can increase fitness by improving the effectiveness of inter-personal
      deception. Ramachandran criticizes Trivers' conjecture, arguing that the costs of
      self-deception outweigh its benefits. We first modify a well-known cognitive
      modularity model of Minsky to formalize a cognitive model of self-deception. We
      then use Byrne's multi-dimensional dynamic character meta-model to integrate the
      cognitive model into an evolutionary hawk-dove game in order to investigate
      Trivers' and Ramachandran's conjectures. By mapping the influence of game
      circumstances into cognitive states, and mapping the influence of multiple
      cognitive modules into player decisions, our cognitive definition of self
      deception is extended to a behavioral definition of self-deception. Our cognitive
      modules, referred to as the hunger and fear daemons, assess the benefits and the
      cost of competition and generate player beliefs. Daemon-assessment of encounter
      benefits and costs may lead to inter-daemonic conflict, that is, ambivalence,
      about whether or not to fight. Player-types vary in the manner by which such
      inter-daemonic conflict is resolved, and varieties of self-deception are modeled
      as type-specific conflict-resolution mechanisms. In the display phase of the
      game, players signal to one another and update their beliefs before finally
      committing to a decision (hawk or dove). Self-deception can affect player
      beliefs, and hence player actions, before or after signaling. In support of
      Trivers' conjecture, the self-deceiving types do outperform the non-self
      deceiving type. We analyse the sensitivity of this result to parameters of the
      cognitive model, specifically the cognitive resolution of the players and the
      influence of player signals on co-player beliefs.

PMID- 11597182
TI  - Pattern analysis in branching and axillary flowering sequences.
AB  - In the architectural approach to the study of plants, a major issue is to analyse
      branching and axillary flowering patterns. Due to the structured expression of
      the branching process and the noisy character of the observed patterns, we
      propose an analysis framework which is both structural and probabilistic. Data
      take the form of sequences which naturally represent the underlying structural
      information of branching and axillary flowering patterns and allow the
      application of a large number of methods ranging from exploratory analysis to
      stochastic modeling. The primary aim of the proposed analysis methods is to
      reveal patterns not directly apparent in the data, and thus to deepen our
      biological understanding of the underlying mechanisms that control the branching
      and the axillary flowering of plants over time and space. The proposed approach
      is illustrated using a set of examples corresponding to different plant species
      and different biological or agronomic objectives.

PMID- 11597183
TI  - Consequences of forced convection for the constraints on size and shape in
      embryos.
AB  - Previously, predictions of the maximum size of biological objects based on oxygen
      availability have been made for both zero and infinite water velocity around the
      object. In reality, however, water velocity is always intermediate between zero
      and infinity. We predicted maximum size and optimal shape of biological objects,
      pending the velocity of water around them. We assumed oxygen inside the object to
      be transported by diffusion and outside the object by diffusion and convection.
      Fick's first law of diffusion describes the inner transport. For the outer
      transport, we relied on semi-empirical relations between mass transport and flow
      conditions (Friedlander's equations). To keep mathematical complexity acceptable,
      we restricted ourselves to the analysis of a sphere and a cylinder in cross flow.
      If water velocity is low, a spherical shape is most favourable for gas exchange.
      If water velocity is high, an elongated and flattened shape is more favourable. A
      size-dependent intermediate velocity exists where shape does not matter (10(-4) m
      s(-1)for teleost embryos). Teleost embryos are typically exposed to flow
      velocities equal to or larger than 10(-4) m s(-1), making an elongated shape more
      favourable than a spherical one. Although teleost eggs are typically spherical,
      the oxygen-consuming embryos inside are indeed elongated.

PMID- 11597184
TI  - Graph models of oncogenesis with an application to melanoma.
AB  - We describe several analytical techniques for use in developing genetic models of
      oncogenesis including: methods for the selection of important genetic events,
      construction of graph models (including distance-based trees, branching trees,
      contingency trees and directed acyclic graph models) from these events and
      methods for interpretation of the resulting models. The models can be used to
      make predictions about: which genetic events tend to occur early, which events
      tend to occur together and the likely order of events. Unlike simple path models
      of oncogenesis, our models allow dependencies to exist between specific genetic
      changes and allow for multiple, divergent paths in tumor progression. A variety
      of genetic events can be used with the graph models including chromosome breaks,
      losses or gains of large DNA regions, small mutations and changes in methylation.
      As an application of the techniques, we use a recently published cytogenetic
      analysis of 206 melanoma cases [Nelson et al. (2000), Cancer Genet.
      Cytogenet.122, 101-109] to derive graph models for chromosome breaks in melanoma.
      Among our predictions are: (1) breaks in 6q1 and 1q1 are early events, with 6q1
      preferentially occurring first and increasing the probability of a break in 1q1
      and (2) breaks in the two sets [1p1, 1p2, 9q1] and [1q1, 7p2, 9p2] tend to occur
      together. This study illustrates that the application of graph models to genetic
      data from tumor sets provide new information on the interrelationships among
      genetic changes during tumor progression.

PMID- 11597185
TI  - Increased coupling between subpopulations in a spatially structured environment
      can lead to population outbreaks.
AB  - Destruction and fragmentation of habitats is widely considered as a major threat
      to biological diversity. A theoretical framework aimed at understanding and
      predicting species responses to these destructive processes is still lacking,
      however. In this paper, the species dynamics in a spatially structured, two
      habitat, patchy environment is considered subject to changes in individual
      migration intensity, i.e. coupling between the habitats. The subpopulation
      dynamics inside each habitat is assumed to be bistable but with different
      parameter values. By using space-discrete/continuous metapopulation dynamic
      models and computer simulations, we show that there can be two principally
      different regimes of metapopulation dynamics. With increasing intensity in the
      interplay between subpopulations, the total abundance can either gradually
      decrease or experience a sudden burst-like increase. This result is shown to be
      robust to the choice of mathematical models (discrete or continuous).
      Particularly, both the "self-excitation" and "self-inhibition" regimes of the
      metapopulation system are robust to variation in habitat size; however, when one
      of the habitats is much smaller than the other, the "self-excitation" regime can
      give way to the "self-inhibition" regime and vice versa.

PMID- 11597177
TI  - Identification and initial characterization of 5000 expressed sequenced tags
      (ESTs) each from adult human normal and osteoarthritic cartilage cDNA libraries.
AB  - OBJECTIVE: To prepare, sequence and analyse adult human cartilage cDNA libraries
      to study the gene expression pattern between normal and osteoarthritic cartilage.
      METHODS: Poly A(+)RNA from adult human normal and osteoarthritic articular
      cartilage was isolated and used to prepare cDNA libraries. Approximately 5000
      ESTs from each library were sequenced and analysed using bioinformatic tools. The
      expression of select genes was confirmed by Northern blot and in situ
      hybridization analysis. RESULTS: Multiple gene families including several
      classical cartilage matrix protein encoding genes were identified. Approximately
      28-40% of the genes sequenced from these libraries were novel, while half of the
      genes encoded known proteins and 4-6% of the genes encoded novel homologs of
      known proteins. Several known genes, whose expression has not been reported
      previously in cartilage, were also identified. We have confirmed the cartilage
      expression of three known (CTGF, CTGF-L and clusterin) and two novel homologs of
      known genes (PCPE-2 and Gal-Nac transferase) by Northern blot and in situ
      hybridization analysis. CONCLUSION: This is the first report of the preparation
      and sequencing of cDNA libraries from adult human normal and osteoarthritic
      articular cartilage. Further analysis of genes identified from these libraries
      may provide molecular targets for diagnosis and/or treatment of osteoarthritis
      (OA).

PMID- 11597186
TI  - Death-inducing tumour necrosis factor (TNF) superfamily ligands and receptors are
      transcribed in human placentae, cytotrophoblasts, placental macrophages and
      placental cell lines.
AB  - Human placentae and two of the cell types in placentae (cytotrophoblasts and
      macrophages) were examined by RT-PCR for transcripts of the eight TNF superfamily
      ligands known to induce death of activated immune cells, tumour cells, and virus
      infected cells (TNFalpha, LT alpha, LT beta, FasL, TRAIL, TWEAK, LIGHT, 4-1BBL).
      Transcripts for all ligands were detected in term placenta but LT alpha and 4
      1BBL were not detected in first trimester placenta. Although term
      cytotrophoblasts contained mRNAs specific for TNF alpha, LT alpha, TWEAK, and 4
      1BBL, messages encoding LT beta, FasL, TRAIL, and LIGHT were absent. In term
      placental macrophages, messages for all ligands except 4-1BBL were present.
      Transcripts for the 14 receptors to which the ligands bind, six of which contain
      death-domains (TNFR1, Fas, DR3, DR4, DR5, DR6), were also identified using RT
      PCR. Term and first trimester placentae contained transcripts for all receptors
      except 4-1BB. Although term cytotrophoblasts lacked receptor mRNA encoding 4-1BB
      and OPG, term placental macrophages lacked DcR1 and OPG. Detection of nearly all
      the death-inducing TNF superfamily ligands and their receptors in human placentae
      implies that these powerful cytokines contribute to programmed or activated cell
      death in this organ.

PMID- 11597187
TI  - Biological characterization of three novel variants of IFN-alpha 13 produced by
      human placental trophoblast.
AB  - Interferon (IFN)-alpha from the human placenta was cloned and expressed with the
      aim to study the antiviral, antiproliferative, and immunostimulatory activities.
      In the present study, we describe three previously unknown sequence variants of
      IFN-alpha 13 originating from the villous trophoblast. The first variant differed
      from IFN-alpha 13 by a Cys99Arg substitution and a 10-amino acid C-terminal
      deletion, which led to a severe reduction of the antiviral and antiproliferative
      potential. The second variant with a Glu32Tyr substitution also displayed
      diminished antiviral and antiproliferative properties, but to a lesser extent
      than the first clone. For the third variant, a Ser25Pro substitution in the N
      terminal part of the protein and two substitutions in the C-terminal part of the
      protein, Arg126Gly and Ala140Gly, resulted in diminished antiviral but not
      antiproliferative properties. Regardless of the altered antiviral and
      antiproliferative properties, all sequence variants demonstrated natural killer
      (NK) cell stimulatory potentials paralleling that of prototype IFN-alpha 13.
      Further studies are needed to gain a better understanding of the functional
      significance of different IFN-alpha subtypes at the maternal-fetal interface, in
      particular in light of the controversial role the NK cells play in the positive
      outcome of pregnancy.

PMID- 11597188
TI  - The characterization of pregnancy associated plasma protein-E and the
      identification of an alternative splice variant.
AB  - We have performed differential display and bioinformatic database mining of the
      placenta, in an attempt to find novel diagnostic markers of pathological
      pregnancies. We have identified a full-length cDNA encoding the preproprotein of
      pregnancy associated plasma protein-E (PAPP-E); a putative metalloprotease, of
      1790-residues with a putative 21-residue signal peptide. An alternatively spliced
      mRNA was found to encode an 826-residue precursor protein corresponding to the N
      terminus of PAPP-E. Both PAPP-E variants were found to be co-expressed abundantly
      in the placenta and non-pregnant mammary gland with low expression in the kidney,
      foetal brain and pancreas. Analysis of the predicted proteins suggests that the
      longer variant be targeted to the nucleus while the shorter variant is secreted
      extracellularly. Gene structure analysis revealed that PAPP-E was encoded on 23
      exons on chromosome 1 and its splice variant on the first five same exons. The
      discovery of the PAPP-E variants will help in the deciphering of the physiology
      of this new family of metzincins in not only the placenta during pregnancy but
      also the mammary gland in breast cancer. The new PAPP-E variants could have the
      potential for the diagnosis of pathological pregnancies including trisomies such
      as Down's syndrome.

PMID- 11597189
TI  - Enrichment and identification of fetal trophoblast cells from first trimester
      maternal cervical lavage and uterine blood specimens.
AB  - First trimester prenatal diagnosis of fetal aneuploidies is an active area of
      research despite years of disappointing data employing maternal peripheral blood
      samples. To remedy this situation we have investigated other first trimester
      maternal specimens attempting to find a consistent fetal cell source. Using our
      previously established positive enrichment procedure along with a commercially
      available depletion method, fetal trophoblast cells were identified employing
      immunocytochemistry using an antibody cocktail or by using mRNA in-situ
      hybridization employing a cocktail of trophoblast specific probes. Fetal origin
      of positively identified cells was verified using interphase fluorescent in-situ
      hybridization (FISH) for X and Y-chromosomes. Artificial model systems were
      established that indicated yields of trophoblast cells and allowed the enrichment
      procedure to be optimized for minimal losses from maternal specimens. We
      demonstrate herein that blood drawn from maternal vessels near the placental
      implantation site to be the most consistent source of fetal cells from any first
      trimester maternal specimen described to date. In addition, a high yield of
      multinucleated syncytiotrophoblast cells was obtained using a cell depletion
      strategy to enrich the target cells. The safety of the procedure or even the
      clinical utility of blood drawn from maternal vessels near the placental
      implantation site is yet to be demonstrated.

PMID- 11597191
TI  - Atrial natriuretic peptide mediated polyuria: pathogenesis of polyhydramnios in
      the recipient twin of twin-twin transfusion syndrome.
AB  - We studied the role of atrial natriuretic peptide (ANP) in the pathophysiology of
      polyhydramnios in monochorionic (MC) twins with and without twin-twin transfusion
      syndrome (TTTS). Matched maternal, fetal blood samples and amniotic fluids (AF)
      were obtained in utero (n=12) and at birth (n=20) from MC twins with TTTS. Blood
      and amniotic fluid samples were also collected from non-TTTS MC twin pairs in
      utero (n=6) and at birth (n=20). In both groups cellular localization of ANP in
      the fetal kidney and heart was performed using anti ANP rabbit polyclonal
      antibody. Concentrations of ANP in pg/ml were determined by radioimmunoassay.In
      recipient fetuses, ANP levels were higher than the donors both in utero (P<
      0.001) and at birth (P< 0.001). No such differences were found between the non
      TTTS twins. In the TTTS group maternal ANP levels were lower than the non-TTTS
      group (P< 0.05). A linear relationship was found between fetal ANP levels and the
      AF volumes removed at fetal blood sampling (r(2)=0.68;P< 0.01, n=12). ANP was
      localized predominantly to the cytoplasm of the distal convoluted tubules of the
      fetal kidney and heart, and the intensity of immunostaining for ANP in kidney and
      heart were markedly greater in the recipient than the donor twin. No such
      differences were found between the twin pairs. These data suggest that
      polyhdramnios in the recipient twin occurs as a consequence of ANP mediated
      increase in fetal urine output and raises the possibility of direct fetal therapy
      with ANP blocking agents.

PMID- 11597190
TI  - Inconsistency of fetal trophoblast cells in first trimester maternal peripheral
      blood prevents non-invasive fetal testing using this cell target.
AB  - We have investigated whether maternal peripheral blood from the first trimester
      of pregnancy is a reliable source of identifiable trophoblast cells. The cells
      were enriched from 30 ml of venous blood, with multiple antibodies shown
      previously to enrich trophoblasts and a new cocktail based on known trophoblast
      surface features. Three different magnetic solid phases were tested to enrich
      trophoblasts, and both positive and negative cell enrichment strategies were
      examined. The cells were identified as trophoblast by morphology coupled with
      immunocytochemistry to co-localize cytokeratin with one of three IGF-II, PAI-1 or
      hPLH proteins or by in-situ hybridization with a mixture of 50 oligos directed to
      eight different expressed genes, alpha-HCG, IGF-II, PAI-1, HASH2, hPLH,
      p57(KIP2), PP5, H-19. While these tools worked beautifully in chorionic villi
      cell/sprout preparations and tissue sections, we could not detect and identify
      any trophoblasts in maternal peripheral blood even if the maternal peripheral
      blood was drawn 5-20 min following termination of pregnancy or from individuals
      maintaining the pregnancy. Based on our own experience and that of some reports
      in the literature, trophoblasts do not appear to be a viable candidate for fetal
      screening using maternal peripheral blood as the source. It is important to note
      that while trophoblast deportation is a biological phenomenon that has been
      described repeatable, they do not provide a means to perform prenatal genetic
      diagnosis.

PMID- 11597192
TI  - Extravillus endovascular implantation site trophoblast invasion is abnormal in
      complete versus partial molar pregnancies.
AB  - This study examines endovascular trophoblast invasion in pregnancies complicated
      by complete hydatidiform mole (CM), partial hydatidiform mole (PM) and non-molar
      abortions (HA). Two hundred consecutive cases from a supra-regional referral
      centre for suspected trophoblastic disease were examined histologically with
      particular regard to the presence or absence of endovascular trophoblast invasion
      of decidual vessels. There were 57 CM, 75 PM and 68 HA. The prevalence of normal
      endovascular invasion of decidual vessels was significantly lower in CM compared
      to all other clinical groups, amongst which there were no significant
      differences. Endovascular trophoblast was identified in about 80 per cent of HA
      and PM moles, compared to only around 25 per cent of CM (Z = -4.0, P< 0.0001).
      The majority of cases of complete mole demonstrated a similar appearance, of
      implantation site showing florid interstitial extravascular trophoblast invasion
      with surrounding of decidual vessels but without normal endovascular trophoblast
      invasion or 'plugging' seen. In many cases, there also appeared to be destruction
      of decidual vessels with interstitial haemorrhage and extensive fresh blood clot
      present in the histological sections. These findings may provide some explanation
      regarding the mechanism of clinical findings in molar pregnancy.

PMID- 11597193
TI  - Correlation of first trimester placental volume and second trimester uterine
      artery Doppler flow.
AB  - Uterine artery Doppler examination can identify impaired trophoblast invasion in
      the second trimester of pregnancy. High resistance and an early diastolic 'notch'
      show insufficient physiological conversion of the spiral arteries. Uterine artery
      Doppler is routinely performed between 22-24 weeks which is relatively late for
      treatment. In this study we wanted to find out whether women with increased
      uterine blood flow resistance at 22 weeks already have reduced placental volumes
      in the first trimester measured with 3D sonography.A total of 1060 women with
      singleton pregnancies had three dimensional (3D) volume measurements of their
      placentae between 11-13 weeks and uterine Doppler scans between 21-22 weeks.
      Stepwise logistic and linear regression analyses were used to show a correlation
      between placental volume (PV) and a CRL dependent placental quotient (PQ) with
      uterine perfusion parameters. Uterine perfusion at 21-22 weeks depends
      significantly on PV or PQ at 11-13 weeks (P< 0.0001 for both) and smoking
      behaviour (P=0.006). The occurrence of a notch also depends significantly on PV
      and PQ (P< 0.0001 for both) and also on gravidity (P< 0.0001) and age (P=0.0007)
      as well as on smoking behaviour (P=0.0094). PV and PQ did not show any dependency
      on age, gravidity, BMI or smoking habits. Placentae of women with high resistance
      uterine perfusion in the second trimester are already remarkably small in the
      first trimester. Placental volumetry is probably an efficient method for early
      and simple identification of impaired trophoblast invasion.

PMID- 11597194
TI  - Evidence of H beta 58, a gene involved in mammalian placental development, in the
      three-toed skink, Chalcides chalcides (Squamata: Scincidae), a viviparous
      placentotrophic reptile.
AB  - The H beta 58 gene, whose disruption in mice causes reabsorption of the embryo at
      9.5 days post-conception, is believed to be essential for development of the
      placenta. Although the H beta 58 gene is well conserved in some Amniota, nothing
      is known about its presence in reptiles, some species of which have developed a
      chorioallantoic placenta. In this work, we investigated the expression of H beta
      58 mRNA and protein in the three-toed skink, Chalcides chalcides. H beta 58
      protein expression was found in the uterine epithelium beginning from the peri
      ovulatory stage. However, it increased strongly at the moment of placental
      formation, when a high level of expression of mRNA and protein was also observed
      in the extra-embryonic membranes. The expression of H beta 58 mRNA and protein
      was maintained, although to a lesser degree, in the placenta during late
      pregnancy. It was also present in the early embryo. Finally, cloning and
      sequencing of a gene fragment revealed strong homology of the reptile gene with
      that of mammals. The high degree of conservation of the gene in amniote
      vertebrates and its presence in a viviparous squamate reptile (as in mammals)
      indicates an important role of this gene in the chorioallantoic placenta
      formation and development.

PMID- 11597195
TI  - Oestrous cycle and pregnancy effects on the distribution of oestrogen and
      progesterone receptors in bovine endometrium.
AB  - Reproductive cyclicity and pregnancy require cell and tissue specific expression
      of oestrogen (OR) and progesterone receptors (PR). To determine the effects of
      cycle day and early pregnancy (days 16-30) on the distribution of OR and PR,
      uteri were collected from cycling (n=39), pregnant (n=14), and steroid-treated
      ovariectomized cattle (n=10). Immunohistochemistry was used to localize OR and
      PR, and staining intensity was scored. Moderate staining for the PR was detected
      in the stroma at proestrus (days 17-20). Expression increased through oestrous,
      reaching maximal levels by metestrus (days 1-6) (P< 0.05). During diestrus (days
      7-16), PR expression was downregulated (P< 0.05). Progesterone receptor
      expression was detected in the luminal epithelium in one of three animals each at
      days 3 and 6 of the oestrous cycle. In pregnant animals only, caruncular stroma
      showed reduced PR staining compared to intercaruncular stroma (P< 0.05).
      Reactivity to the OR antibody in cycling animals was detected in the stroma and
      glandular epithelium. Levels increased through proestrus and oestrous, were
      maximal during metestrus (P< 0.05), and decreased during diestrus (P< 0.05).
      Interestingly, there was transient upregulation in the luminal epithelium on day
      16 or day 14 (P< 0.05). This was not evident at day 16 of pregnancy, although
      some OR reactivity was present in stroma and glands. By day 18 of pregnancy OR
      were undetectable (P< 0.05). Oestrogen-treated ovariectomized animals had
      increased OR and PR expression in comparison to progesterone treated cows (P<
      0.05). Untreated ovariectomized cows showed constitutive steroid receptor
      expression. These results support the widely accepted role for sex steroids in
      the regulation of their receptors and indicate that there is paracrine regulation
      of steroid receptor expression in the bovine uterus.

PMID- 11597196
TI  - A structural and immunological study of chorionic gonadotrophin production by
      equine trophoblast girdle and cup cells.
AB  - Equine chorionic gonadotropin (eCG) production by the fetally derived endometrial
      cups appears to be necessary for the establishment and maintenance of normal
      equine pregnancy. Starting at about the 27th day of pregnancy, an equatorial band
      of trophectodermal cells on the surface of the spherical conceptus forms the
      chorionic girdle. This girdle consists initially of flat trophectodermal
      epithelium which corrugates into folds as the cells proliferate. The folds are
      then pressed against the uterine epithelium by expansion of the conceptus. The
      cells on the apices of the folds become binucleate before they start to invade
      the endometrium at days 35-37. Ultrastructural immunogold labelling shows that
      they begin to synthesize eCG as early as day 32, before they migrate into and
      through the maternal epithelium. Clusters of the girdle binucleate cells
      penetrate deep into the endometrium. The mature cup cell has a cytoplasm full of
      mitochondria, rough endoplasmic reticulum cisternae, a large Golgi apparatus and
      a strong immunoreactivity for the glucose transporter 1 isoform on its
      plasmalemma. Immunocytochemistry also demonstrates that eCG is localized in the
      Golgi cisternae, and in small dense granules similar to those found in the
      migrating girdle cell and present both in the Golgi region and at the peripheral
      plasmalemma. Release of eCG would therefore seem to be by the usual exocytotic
      mechanism as found for other protein hormones. The small size and absence of any
      significant accumulation of eCG-containing granules are in marked contrast to the
      numerous large luteinizing hormone (eLH) containing granules in the equine
      pituitary gonadotroph, although both hormones, eLH and eCG, show complete
      identity at the amino acid sequence level. These morphological indicators suggest
      that the cup cell secretes eCG constitutively (that is, continuously), with no
      requirement for secretagogues, whereas in the pituitary cell the regulated
      pathway is utilized capable of massive secretion under appropriate stimulation.

PMID- 11597197
TI  - Characteristics of calcium uptake by BeWo cells, a human trophoblast cell line.
AB  - Placental transfer of maternal calcium (Ca(2+)) is a crucial process for fetal
      development although the biochemical mechanisms responsible for this transfer are
      largely unknown. We have investigated the characteristics of Ca(2+)uptake by the
      human placental trophoblast cell line BeWo. The kinetics studies revealed an
      active extracellular Ca(2+)uptake by BeWo cells, which was rapid in the first 2
      min (initial velocity (V(i)) of 4.17+/-0.25 nmol/mg/min), and showed a subsequent
      plateau. Uptake experiments performed at V(i)with increasing concentrations of
      Ca(2+)resulted in a typical saturation curve (K(m)of 0.54+/-0.07 m m and V(max)of
      7.07+/-0.28 nmol/mg protein/min). Lowering the pH of the incubation medium from
      7.4 to 5.5 led to Ca(2+)uptake inhibition of 40-50 per cent. The presence of
      voltage-sensitive (l -type) Ca(2+)channels in BeWo cells was demonstrated by
      Western blot. Therefore, the implication of such channels in basal Ca(2+)uptake
      of BeWo cells was investigated. Cell depolarization with extracellular high
      potassium concentration (40 m m), and hyperpolarization with extracellular high
      chloride concentration (60 m m) or with valinomycin (10 microm) did not influence
      the basal Ca(2+)uptake of BeWo cells. The L-type Ca(2+)channel modulators (Bay K
      8644 and Nitrendipine) had no effect on the Ca(2+)uptake. An antagonist of
      receptor-mediated, store-operated and voltage-gated Ca(2+)channels (SKF-96365)
      also did not modulate the Ca(2+)uptake of BeWo cells. Therefore, our results
      indicate that the basal Ca(2+)uptake of BeWo cells is inhibited by lowering pH of
      the incubation medium, is voltage independent, and is not influenced by l -type
      Ca(2+)channel and capacitative Ca(2+)conductance modulators.

PMID- 11597198
TI  - Water channel proteins AQP3 and AQP9 are present in syncytiotrophoblast of human
      term placenta.
AB  - The syncytiotrophoblast of human term placenta (HST) is a continuous,
      multinucleated structure with minimal tight junctions, which results from the
      fusion of the underlying cytotrophoblast cells. Consequently, the transport of
      metabolites, ions and water from mother to fetus could take place primarily via
      transcellular routes. Transcellular water flux may be facilitated by aquaporins,
      membrane proteins functioning as water channels that are widely expressed in
      cells and tissues. Here, we report the presence of AQP3 and AQP9 in the apical
      membranes of HST using RT-PCR, immunoblotting and immunohistochemistry. Since
      AQP3 is not only a water channels, but also permits the rapid passage of both
      urea and glycerol, while AQP9 also mediates the passage of carbamides, polyols,
      purines, and pyrimidines, we have speculated that these proteins could be
      involved in the transport of water and solutes from mother to fetus.

PMID- 11597199
TI  - Immuno-electron microscopic localization of endothelial nitric oxide synthase in
      human placental terminal villous trophoblasts-normal and pre-eclamptic pregnancy.
AB  - We demonstrated the subcellular localization of endothelial nitric oxide synthase
      (eNOS) in human placental terminal villous trophoblasts at near term period, and
      compared the distribution pattern with that in pre-eclamptic trophoblasts, using
      immunogold electron microscopy. Immunolabelling for eNOS was visible markedly in
      the syncytial microvilli and syncytial cytoplasm. Semiquantitative analysis
      showed that the concentration and the distribution pattern of gold particles for
      eNOS did not significantly differ between normal and pre-eclamptic placental
      trophoblasts. These results indicated that syncytiotrophoblastic microvilli and
      cytoplasm were the subcellular localization sites of syncytium-derived eNOS in
      terminal villi, and that there were no significant differences in this eNOS
      subcellular distribution pattern between normal and pre-eclamptic
      syncytiotrophoblasts in regard to immunohistochemically detectable eNOS.

PMID- 11597200
TI  - Maternal age and traits of offspring in humans.

PMID- 11597201
TI  - Probing sponge-derived terpenoids for human 15-lipoxygenase inhibitors.
AB  - A human 15-lipoxygenase (15-HLO) assay has been employed to discover new marine
      sponge-derived bioactive compounds. Extracts from two different sponges, Jaspis
      splendens (order Choristida, family Jaspidae) and Suberea sp. (order Verongida,
      family Aplysinellidae), exhibited potent IC(50) values of 0.4 and 0.1 microg/mL,
      respectively. Both are sources of terpenoids, and the former is a known source of
      (+)-jasplakinolide (7), which is inactive as a 15-HLO inhibitor. The terpenoids
      included (+)-(5S,6S)-subersin (1, IC(50) > 100 microM), (-)-(5R,10R)-subersic
      acid (2, IC(50) = 15 microM), jaspaquinol (3, IC(50) = 0.3 microM), and (-)
      jaspic acid (4, IC(50) = 1.4 microM). Structure elucidations and lipoxygenase
      activity studies of these compounds are reported.

PMID- 11597202
TI  - Rhodium-catalyzed asymmetric 1,4-addition of organoboron reagents to 5,6-dihydro
      2(1H)-pyridinones. Asymmetric synthesis of 4-aryl-2-piperidinones.
AB  - Catalytic asymmetric synthesis of 4-aryl-2-piperidinones was realized for the
      first time by asymmetric 1,4-addition of arylboron reagents to 5,6-dihydro-2(1H)
      pyridinones in the presence of a chiral bisphosphine-rhodium catalyst. In the
      reaction introducing 4-fluorophenyl group, the use of 4-fluorophenylboroxine and
      1 equiv (to boron) of water at 40 degrees C gave the highest yield of the
      arylation product with high enantioselectivity (98% ee). The (R)-4-(4
      fluorophenyl)-2-piperidinone obtained here is a key intermediate for the
      synthesis of (-)-Paroxetine.

PMID- 11597203
TI  - Supramolecular daisy chains.
AB  - Two series of self-complementary daisy chain monomers, in which a secondary
      ammonium ion-containing arm is grafted onto a macrocycle with either a [24]- or
      [25]crown-8 constitution, have been synthesized. In the solid- and 'gas'-phases,
      the parent [24]crown-8-based monomer forms dimeric superstructures, as revealed
      by X-ray crystallography and mass spectrometry, respectively. Elucidation of the
      complicated solution-phase behavior of this compound was facilitated by the
      synthesis and study of both deuterated, and fluorinated, analogues. These
      investigations revealed that the cyclic dimeric superstructure also dominates in
      solution, except when extremes of either concentration (low), temperature (high),
      or solvent polarity (highly polar, e.g., dimethyl sulfoxide) are employed.
      Whereas, upon aggregation, the [24]crown-8-based daisy chain monomers have the
      capacity to form stereoisomeric superstructures further complicating the study of
      this series of compounds. The assembly of [25]crown-8-based monomers gives only
      achiral superstructures. The weaker association exhibited between secondary
      dialkylammonium ions and crown ethers with a [25]crown-8 constitution, however,
      resulted in limited oligomerization--only dimeric and trimeric superstructures
      were formed at experimentally attainable concentrations--of [25]crown-8-based
      daisy chain monomers.

PMID- 11597204
TI  - 3,4-Alkylenedioxypyrroles: functionalized derivatives as monomers for new
      electron-rich conducting and electroactive polymers.
AB  - New functionalized derivatives of 3,4-ethylenedioxypyrrole (EDOP, 5a) and 3,4
      (1,3-propylenedioxy)pyrrole (ProDOP, 5b) as especially electron-rich monomers
      which yield highly electroactive and stable conducting polymers useful for a
      diverse set of applications have been synthesized. N-Alkylations of ProDOP were
      carried out to yield a variety of ProDOP derivatives having alkyl,
      sulfonatoalkoxy, glyme, and glyme alcohol pendant chains. Iodization of EDOP and
      ProDOP via iodo-decarboxylation afforded iodo-functionalized derivatives useful
      for subsequent aryl coupling chemistry. N-Protection and formylation of EDOP,
      followed by Knoevenagel condensation of the resultant 2-formyl-EDOP with aryl
      acetonitrile derivatives, led to 1-cyano-2-(2-(3,4-ethylenedioxypyrryl))-1-(2
      thienyl)vinylene (23) (Th-CNV-EDOP) and 1-cyano-2-(2-(3,4-ethylenedioxypyrryl))-1
      (2-(3,4-ethylenedioxythienyl)vinylene (26) (EDOT-CNV-EDOP). A 14-crown-4-ether 34
      based dioxypyrrole was synthesized with a cavity potentially useful for lithium
      ion coordination and sensing in the resultant electroactive polymer. C-Alkylated
      ProDOPs (43a, 43b, and 43c) containing octyl, ethylhexyl, and dioctyl
      substituents appended to the central methylene of the propylene bridge, were
      prepared as monomers for potentially soluble pi-conjugated polymers.

PMID- 11597205
TI  - Revisiting Markovnikov addition to alkenes via molecular electrostatic potential.
AB  - Molecular electrostatic potentials (MESP) surrounding the pi-region of several
      substituted ethylenes (CH(2)CHR) have been characterized by locating the most
      negative-valued point (V(min)) in that region. The substituents have been
      classified as electron donating and withdrawing on the basis of the increase or
      decrease in the negative character of V(min) in these systems as compared to
      ethylene. The values of V(min) show a good linear correlation with the Hammett
      sigma(p) constants, suggesting that the substituent electronic effects in
      substituted ethylenes and substituted benzenes are basically similar. With
      electron-donating substituents, the position of MESP minimum is closer to the
      unsubstituted carbon facilitating the pi-complex formation of it with HCl at this
      site. Such a regiospecific pi-complex formation is found to favor the formation
      of Markovnikov-type transition state for the addition of HCl to CH(2)CHR. For the
      electron-withdrawing substituents, the V(min) location is almost equidistant and
      farther from the ethylenic carbon atoms. This and the less negative V(min) values
      account for the less regiospecific CH(2)CHR...HCl pi-complexes as well as the
      transition states for the HCl addition to CH(2)CHR when R is an electron
      withdrawing group. The interaction energy (E(int)) between CH(2)CHR and HCl for
      the formation of the CH(2)CHR...HCl pi-complex shows a good linear correlation
      with the corresponding V(min) value.

PMID- 11597206
TI  - NMR diffusion spectroscopy as a measure of host-guest complex association
      constants and as a probe of complex size.
AB  - The complexes of cyclohexylacetic acid and cholic acid with beta-cyclodextrin
      were studied by NMR diffusion coefficient measurements. The diffusion coefficient
      of the 1:1 cyclohexylacetic acid/beta-cyclodextrin complex, K(a) = 1800 +/- 100
      M(-1), is slightly slower (3.23 +/- 0.07 x 10(-6) cm(2) s(-1)) than that of beta
      cyclodextrin (3.29 +/- 0.07 x 10(-6) cm(2) s(-1)). The diffusion coefficient of
      the 1:1 cholic acid/beta-cyclodextrin complex, K(a) = 5900 +/- 800 M(-1), is
      significantly slower (2.93 +/- 0.07 x 10(-6) cm(2) s(-1)) than that of beta
      cyclodextrin. The results indicate that caution should be exercised when studying
      host-guest complexation by the so-called 'single point' technique. A novel data
      treatment is introduced which takes into account the diffusion behavior of all of
      the species when determining K(a). Experimentally determined diffusion
      coefficients of complexes are also a useful probe of the size of host-guest
      complexes.

PMID- 11597207
TI  - Photochemically induced electron transfer (PET) catalyzed radical cyclization: a
      practical method for inducing structural changes in peptides by formation of
      cyclic amino acid derivatives.
AB  - A new radical cyclization reaction of unsaturated amino acid derivatives is
      presented. The reaction is induced by photoelectron transfer (PET) catalysis and
      proceeds, in comparison to commonly applied methods, under mild, nonoxidizing,
      and nontoxic conditions in neutral medium. This type of radical cyclization
      reaction can be used in peptide chemistry for inducing structural changes in
      peptides.

PMID- 11597208
TI  - Oxa bowls: synthesis and C-H...O mediated solid state structure of pentaoxa-[5]
      peristylane.
AB  - We have conceptualized [n]-oxa-[n]-peristylanes as a new family of "oxa bowls"
      having a crownlike shape and potential C(nv)() symmetry. Recognizing their
      equivalence to the corresponding [n]-formyl-[n]-cycloalkanes, we have conceived
      of a general synthetic strategy in which "intramolecular cascade acetalizations"
      constitute the pivotal step. As our first synthetic effort, we describe the
      synthesis of pentaoxa-[5]-peristylane 3b from the readily available Diels-Alder
      adduct 10 of 5,5-dimethoxy-tetrachlorocyclopentadiene and maleic anhydride. The
      norbornyl framework of 10 serves as the rigid structural matrix to build the
      stereochemical features and latent aldehyde functionalities as in 9 through a
      series of functional group adjustments. Ozonation of 9 furnished 3b in a one-step
      transformation in which five tetrahydrofuran rings were generated. While 3b
      exhibited C(5v) symmetry in solution, its symmetry in the solid state was
      observed to be C(s) by X-ray crystallography. In the solid state, 3b is endowed
      with a multicolumnar architecture, whose distinctive features include C-H...O
      interactions involving the less acidic cyclopentane hydrogens. Indeed, all the 10
      CH moieties and 5 oxygen atoms (through both the lone pairs) of 3b
      (C(10)H(10)O(5)) are involved in short C-H...O contacts (strong and soft) and its
      crystal structure indicates marked proclivity toward maximal hydrogen bonding.

PMID- 11597209
TI  - Oxa bowls: studies toward hexaoxa-[6]-peristylane. Synthesis of a seco-derivative
      of hexaoxa-[6]-peristylane.
AB  - When the concept of equivalency of all-cis-[n]-formyl-[n]-cycloalkanes with [n]
      oxa-[n]-peristylanes was followed, an approach to the "oxa bowl" hexaoxa-[6]
      peristylane 4a was delineated. This required an access to all-cis-cyclohexane
      hexacarbaldehyde 5, which could be subjected to a 6-fold intramolecular
      acetalization cascade. A readily available Diels-Alder adduct of
      cyclooctatetraene and maleic anhydride was chosen as the starting material and
      was elaborated to the endo, endo-tetraene 6 in which all the six aldehyde
      functionalities are present in a latent form with cis orientation in a locked
      cyclohexane ring. Although ozonolysis of 6 has so far led only to intractable
      products, the novelty and brevity of our approach have been demonstrated through
      the intramolecular acetalizations through ozonolysis in 7 and 15, leading to oxa
      bowls 9 (seco-hexaoxaperistylane) and 16, respectively. The formation of 9 and 16
      requires the generation of five tetrahydrofuran and four oxacyclic rings,
      respectively, in a single-pot operation.

PMID- 11597210
TI  - Comparison of quantum chemical parameters and Hammett constants in correlating
      pK(a) values of substituted anilines.
AB  - Historically, Hammett constants have been extremely effective in describing the
      influence of substituents on chemical reactivity and other physical and chemical
      properties, whereas variables derived from quantum chemical calculations have
      generally been less effective. Taking the experimental pK(a)s of substituted
      anilines as a representative physicochemical property, five ab initio quantum
      chemical indices are compared for effectiveness as one-parameter regression
      descriptors for pK(a). All of the tested descriptors performed well for a set of
      19 mono-, 13 di-, and 4 trisubstituted anilines, and two performed somewhat
      better than the traditional Hammett sigma constants. Among the calculated
      quantities, the best representation of the aniline pK(a)s is produced by the
      minimum average local ionization energy on the molecular surface.

PMID- 11597211
TI  - Functionalized iminium salt systems for catalytic asymmetric epoxidation.
AB  - A range of dihydroisoquinolinium salts containing alcohol, ether, and acetal
      functionalities in the nitrogen substituent has been prepared and tested as
      asymmetric epoxidation catalysts, providing ee's of up to ca. 60%.

PMID- 11597212
TI  - Transition metal-catalyzed [4 + 2 + 2] cycloadditions of bicyclo[2.2.1]hepta-2,5
      dienes (norbornadienes) and bicyclo[2.2.2]octa-2,5-dienes.
AB  - The transition-metal-catalyzed [4 + 2 + 2] cycloadditions of norbornadienes,
      bicyclo[2.2.2]octa-2,5-diene, and benzobarrelene with 1,3-butadienes proceed in
      excellent yields using cobalt-based catalytic systems. Two key distinctions
      between these [4 + 2 + 2] cycloadditions and the corresponding transition-metal
      catalyzed [2 + 2 +2] reactions of norbornadiene are the requirement of a bimetal
      catalytic system with a bisphosphine ligand for the former and exclusive
      regioselectivity in the [4 + 2 + 2] reaction of 2-substituted norbornadienes to
      produce 1-substituted adducts. These distinctions may indicate two distinct
      mechanisms for the [4 + 2 + 2] and [2 + 2 + 2] reactions.

PMID- 11597213
TI  - Opening the [4 + 2 + 2] cycloadducts of bicyclo[2.2.1]hepta-2,5-dienes
      (norbornadienes) to cis-fused bicyclo[5.3.0]decanes.
AB  - Tetracyclo[5.4.0.0.(2,4)0(3,7)]undec-9-enes, prepared by the transition-metal
      catalyzed [4 + 2 + 2] homo-Diels-Alder reactions of norbornadiene and 1,3
      butadienes, can be opened using either acid-promoted or Zeise's dimer-mediated
      cyclopropane ring cleavage, ultimately leading to cis-fused bicyclo[5.3.0]decanes
      (perhydroazulenes). Stereoselective functionalization of the olefin unit in the
      tetracycloundecenes to an alcohol or diol prior to ring opening is tolerated by
      the Zeise's dimer ([Pt(C(2)H(4))Cl(2)](2)) catalyst to yield highly
      functionalized bicyclo[5.3.0]decanes, which form the core structure of numerous
      sesquiterpenes.

PMID- 11597214
TI  - Zinc-catalyzed oxidation of 5-S-cysteinyldopa to 2,2'-bi(2H-1,4-benzothiazine):
      tracking the biosynthetic pathway of trichochromes, the characteristic pigments
      of red hair.
AB  - Trichochromes, the peculiar pigments of red human hair, featuring the
      Delta(2,2)(')-bi(2H-1,4-benzothiazine) skeleton, are known to arise from
      cysteinyldopas, mainly the 5-S-isomer (5). However, the mode of formation and the
      direct precursors have remained largely undefined. To fill this gap, we
      investigated the oxidation of 5 in air or with chemical and enzymatic agents
      under biomimetic conditions. In the presence of zinc ions, which occur in
      epidermal tissues at significant concentrations, the reaction course is diverted
      toward the formation of a labile 3-carboxy-2H-1,4-benzothiazine intermediate
      (11), which was identified by direct NMR analysis. Structural formulation was
      supported by characterization of the analogous compound 13 isolated from
      oxidation of the model 5-methyl-3-S-cysteinylcatechol (12) after methylation. In
      the further stages of the oxidation, diastereomeric 2,2'-bi(2H-1,4-benzothiazine)
      15 and 14 were obtained from 5 and 12, respectively, the reaction proceeding at a
      higher rate and to a greater extent in the presence of acids. The dimers were
      shown to readily convert to each other in the presence of acids. In the case of
      the methylated dimers 14, a 2,2'-bi(4H-1,4-benzothiazine) intermediate (16) was
      isolated and characterized. In acidic media, trichochrome C (1a), the most
      abundant in red human hair, was smoothly formed from aerial oxidation of 15, and
      under similar conditions, trichochrome-related products (17 and 18) were obtained
      from 14 prior to or after methylation. The presence of 1a and precursors 5 and 15
      was investigated by HPLC analysis of red hair samples following mild proteolytic
      digestion. On the basis of these data, a likely biosynthetic route to
      trichochrome pigments of red human hair is depicted.

PMID- 11597215
TI  - Reductive fragmentation of carbohydrate anomeric alkoxy radicals. Synthesis of
      alditols with potential utility as chiral synthons.
AB  - A series of anomeric nitrate esters and N-phthalimido glycosides of carbohydrates
      in furanose and pyranose forms have been synthesized in order to generate the
      corresponding alkoxy radicals and study the C1-C2 fragmentation reaction under
      reductive conditions. This reaction constitutes a two-step method for the
      transformation of carbohydrates into the corresponding alditols with one less
      carbon. Using this methodology, interesting four- and five-carbon building blocks
      for natural products synthesis possessing D-erythritol, D-threitol, D-xylitol,
      and D-arabinitol stereochemistry have been prepared. The synthesis of 1,2-O
      isopropylidene-beta-L-threose (40) and 1-acetamido-2,4,5-tri-O-acetyl-D
      arabinitol (50) have also been achieved from 1,2:5,6-di-O-isopropylidene-beta-D
      glucofuranose and 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-D-glucopyranose,
      respectively.

PMID- 11597216
TI  - Trimethylsilyl group migrations in cryogenic ozonolysis of trimethylsilylethene:
      evidence for nonconcerted primary ozonide decomposition pathway.
AB  - The identification of trimethylsiloxy-1,2-dioxetane and 2
      trimethylsilyloperoxyacetaldehyde and assignment of trimethylsiloxymethyl formate
      as products of the low-temperature ozonolysis of trimethylsilylethene demonstrate
      feasibility of migrations of trimethylsilyl group in a dioxygen-centered
      (oxyperoxy) diradical produced via a homolytic cleavage of each of both O-O bonds
      in the primary ozonide. The results provide the first experimental evidence on
      the nonconcerted decomposition of the primary ozonide.

PMID- 11597217
TI  - Furanodictine A and B: amino sugar analogues produced by cellular slime mold
      Dictyostelium discoideum showing neuronal differentiation activity.
AB  - We investigated the constituents of Dictyostelium discoideum to clarify the
      diversity of secondary metabolites of Dictyostelium cellular slime molds and to
      explore biologically active substances that could be useful in the development of
      novel drugs. From a methanol extract of the multicellular fruit body of D.
      discoideum, we isolated two novel amino sugar analogues, furanodictine A (1) and
      B (2). They are the first 3,6-anhydrosugars to be isolated from natural sources.
      Their relative structures were elucidated by spectral means, and the absolute
      configurations were confirmed by asymmetric syntheses of 1 and 2. These
      furanodictines potently induce neuronal differentiation of rat pheochromocytoma
      (PC-12) cells.

PMID- 11597218
TI  - The preparation and intra- and intermolecular addition reactions of acyclic N
      acylimines: application to the synthesis of (+/-)-sertraline.
AB  - Intramolecular endo-cyclization reactions of N-acyliminium ions have seen wide
      application for the synthesis of heterocyclic compounds. The corresponding
      exocyclic variant, which would provide 1-aminotetralin derivatives, for example,
      has little precedent. We have discovered that acyclic N-acylcarbamates can be
      readily reduced to the corresponding N-acylhemiaminal derivatives in high yield
      using DIBAL as the reducing agent. These intermediates are remarkably stable and,
      if desired, can be purified and stored. The acyclic N-acylhemiaminals undergo
      both intra- and intermolecular nucleophilic addition reactions mediated by strong
      Lewis acids, such as TiCl(4). Diastereoselectivity, induced either by a
      substituent on the newly formed ring, or by utilizing a chiral ester on the
      carbamic acid, was disappointingly low. This methodology was successfully applied
      to the synthesis of the racemic form of the marketed antidepressant sertraline.

PMID- 11597219
TI  - Reaction of arylsulfonylhydrazones of aldehydes with alpha-magnesio sulfones. A
      novel olefin synthesis.
AB  - Reactions of representative tosylhydrazones of aldehydes and ketones with alpha
      metalated sulfones were examined in order to develop a practical olefination
      method. Treatment of aldehyde tosylhydrazone 2 with an excess of alpha-lithiated
      methyl phenyl or dimethyl sulfones yielded 3a. The reaction of 2 with sterically
      unhindered lithiated alkyl sulfones gave mixtures of the respective olefination
      products 3b-d along with the Shapiro fragmentation product 4. Sterically hindered
      lithiated sulfones afforded Shapiro products exclusively. In contrast, aldehyde
      tosylhydrazones 2 or 6 in reactions with a variety of alpha-magnesio primary or
      secondary alkyl sulfones gave olefination products 3a-j and 7a-c in high yields
      (Tables 1 and 2). beta-Branched alkyl sulfones afforded predominantly (E)
      alkenes, whereas unhindered primary sulfones gave mixtures of (E)- and (Z)
      alkenes with low selectivity. Reaction of the 2,4,6
      triisopropylbenzenesulfonylhydrazone (trisylhydrazone) of cyclodecanone 11c with
      alpha-magnesio methyl phenyl sulfone afforded the methylidene derivative 12a
      contaminated with the Shapiro product 13. Tosylhydrazone 2 resisted reaction with
      i-PrMgCl and gave only a small amount of the addition product in reaction with
      Bu(2)Mg. Some mechanistic aspects of the reaction of tosylhydrazones with
      organomagnesium compounds are discussed.

PMID- 11597220
TI  - Facile approach to enantiomerically pure alpha-amino ketones by Friedel-Crafts
      aminoacylation and their conversion into peptidyl ketones.
AB  - In this article we describe a versatile and straightforward preparative approach
      to chiral aryl alpha-amino ketones via a Friedel-Crafts-type reaction of stable
      and enantiomerically pure N-Fmoc protected L-amino acid chlorides with toluene in
      the presence of aluminum trichloride. The developed methodology provided aryl
      alpha-amino-p-methylphenyl ketones, which can be obtained and isolated as free
      bases or recovered as their N-acetyl derivatives, after treatment with acetic
      anhydride in chloroform at room temperature, subsequent to the Lewis acid induced
      removal of the 9-fluorenylmethoxycarbonyl protecting group. The Friedel-Crafts
      like process and the cleavage of the amino function masking group can selectively
      be performed since, as verified in all cases, the alpha-aminoacylation step
      occurred with kinetics that were faster than those required to remove the N
      protection. The presented approach was also explored as a facile and useful
      synthetic tool for the preparation of optically pure ketone di- and tripeptides.
      These compounds can be obtained in exceptionally overall yields without need of
      chromatographic purification. Moreover, either aryl alpha-amino ketones or
      modified di- and tripeptides, in all cases, can be isolated in very high chemical
      and optical purity without recourse to resolution of diastereomeric mixtures,
      since the chiralities of the asymmetric amino acid educts were completely
      conserved throughout the entire process.

PMID- 11597221
TI  - Synthesis and metal-ion binding properties of monoazathiacrown ethers.
AB  - Synthetic procedures for monoazathiacrown ethers were explored, and
      monoazatrithia-12-crown-4, monoazatetrathia-15-crown-5, and monoazapentathia-18
      crown-6 were obtained in moderate yields by the reaction of bis(2
      chloroethyl)amine with the appropriate dithiols in the presence of lithium
      hydroxide in THF. To evaluate metal-ion binding properties of the
      monoazathiacrown ethers by solvent extraction, lipophilic dodecyl and dodecanoyl
      groups were incorporated onto the monoazathiacrown ethers. The solvent extraction
      experiments suggested that monoazathiacrown ethers have Ag(+) and Hg(2+)
      selectivities and that the relative selectivity between Ag(+) and Hg(2+) depends
      on their nitrogen atom properties and numbers of sulfur atoms reflecting the
      respective affinities of nitrogen and sulfur atoms to Hg(2+) and Ag(+). An
      interesting ability to bind Mg(2+) was observed in the case of N-dodecyl
      monoazatrithia-12-crown-4.

PMID- 11597222
TI  - Efficient photocyclization of o-alkylbenzaldehydes in the solid state: direct
      observation of E-xylylenols en route to benzocyclobutenols.
AB  - The photocyclization to benzocyclobutenols of o-alkyl aromatic aldehydes that are
      predestined for gamma-hydrogen abstraction is found to occur efficiently in the
      solid state; in contrast, solution-phase photolysis is known to afford a mixture
      of several products. It is shown that mesitaldehyde, which is a liquid, also
      undergoes efficient cyclization when subjected to photolysis as a solid inclusion
      complex. The marginal energy differences in the relative energies of the E-enols
      and the corresponding cyclobutenols in the case of cyano-substituted
      mesitaldehydes has permitted direct observation, for the first time, of the E
      enols en route to benzocyclobutenols. The AM1 calculations suggest that the cyano
      substitution causes intrinsic stabilization of the E-enols relative to the
      corresponding cyclobutenols, while the bromo groups do the opposite. The lack of
      observation of the red color in bromo- and formyl-substituted aldehydes is
      attributed to rapid cyclization of the E-enols to the their respective
      cyclobutenols even at low temperatures.

PMID- 11597224
TI  - Reactive enols in synthesis 2. Synthesis of (+)-latifolic acid and (+)
      latifoline.
AB  - We describe a short, enantioselective synthesis of the naturally occurring
      pyrrolizidine alkaloid (+)-latifoline (1) employing a tandem [3,3] sigmatropic
      rearrangement/[1,2] allyl shift as a key step in constructing (+)-latifolic acid
      (4).

PMID- 11597223
TI  - Electroytic partial fluorination of organic compounds. 52. Regio- and
      diastereoselective anodic fluorination of thiazolidines.
AB  - Anodic fluorination of N-benzoyl, N-acethyl-, and N-formylthiazolidine derived
      from L-cysteine was carried out in dimethoxyethane (DME) and acetonitrile
      containing various supporting fluoride salts using an undivided cell. Highly
      regioselective fluorination proceeded to provide the corresponding 5
      monofluorinated thiazolidine derivatives in good yields in DME, and the
      diastereoselectivitiy was moderate to high regardless of the supporting fluoride
      salts. The diastereoselectivitiy of the fluorination was greatly affected by the
      bulkyness of the subsitituent on the nitrogen atom, and N-benzoylthiazolidine
      gave much higher diastereoselectivity compared with N-formyl derivative. The
      fluorination of the thiazolidines was not achieved by commercially available
      fluorinating reagents such as N-fluoropyridinium salts.

PMID- 11597225
TI  - Electrolytic partial fluorination of organic compounds. 54. Anodic mono- and
      trifluorination of thiochroman-4-one derivatives and the factors affecting
      product selectivity.
AB  - Anodic fluorination of (E)-3-benzylidene-2,3-dihydrothiochroman-4-one and 3
      benzyl-1-thiochromone derivatives under a variety of electrolytic conditions was
      found to provide selectively or exclusively the same fluorinated products: (E)-3
      benzylidene-2,3-dihydro-2-fluorothiochroman-4-ones. In addition, di- and
      trifluorinated derivatives were also obtained depending on the starting
      heterocycles and electrolytic conditions. The factors affecting the product
      selectivity were also examined.

PMID- 11597226
TI  - Self-assembly of novel [3]- and [2]rotaxanes with two different ring components:
      donor-acceptor and hydrogen bonding interactions and molecular-shuttling
      behavior.
AB  - Three of the first kind of hetero[3]rotaxanes, which comprise one linear
      component and one neutral and one tetracationic ring component, have been
      assembled by using the intermolecular hydrogen bonding and donor-acceptor
      interactions. Three neutral [2]rotaxanes and three tetracationic [2]rotaxanes
      have also been synthesized as intermediate products or for the sake of property
      comparison. The linear molecules are incorporated with two glycine subunits, for
      templating the formation of the neutral tetraamide cyclophane, and one or two
      hydroquinone subunits, for inducing the formation of the tetracationic
      cyclophane. Variable-temperature (1)H NMR investigation reveals that the
      shuttling behavior of the tetracationic ring component along the linear component
      is substantially influenced by the existence of the neutral ring component. The
      spatial repelling interaction of the neutral ring on the electron-deficient
      tetracationic ring simultaneously weakens the latter's "positioning" tendency at
      both electron-rich hydroquinone sites of the linear component. As a result, the
      activation energy associated with the shuttling process of the tetracationic ring
      between the two hydroquinone sites is remarkably reduced in comparison to that of
      the shuttling process of the corresponding neutral ring-free [2]rotaxanes. For
      the first time, the rotation of the dipyridinium subunit around the axis formed
      by the two methylene groups connecting them within the tetracationic cyclophane
      has been investigated by variable-temperature (1)H NMR spectroscopy and the
      associated kinetic data have also been successfully obtained. Furthermore, the UV
      vis and fluorescent properties of the new [2]- and [3]rotaxanes have been
      studied. The results demonstrate that [3]rotaxanes with different ring components
      possess unique kinetic features that are not available in [3]rotaxanes with
      identical ring components.

PMID- 11597227
TI  - Influence of chirality of the preceding acyl moiety on the cis/trans ratio of the
      proline peptide bond.
AB  - We report that the cis/trans ratio of the proline peptide bond can be strongly
      influenced by the chirality of the acyl residue preceding proline. Acyl moieties
      derived from (2S)-2,6-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylic
      acid (8) and (2R)-3-methoxy-2-methyl-2-(4-methyl-2-nitrophenoxy)-3-oxopropanoic
      acid (5) in acyl-Pro molecules influence isomerization of the proline peptide
      bond constraining the omega dihedral angle to the trans orientation. Structures
      of benzyl (2S)-1-([(2S)-2,6-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2
      yl]carbonyl)-2-pyrrolidinecarboxylate (3) derived from 2D (1)H NMR conformational
      analysis and crystallographic data exhibit only the trans conformation of proline
      peptide bond. On the other hand the diastereomer 4, which contains an (R) acyl
      moiety, exhibits two sets of signals in (1)H NMR spectra. The signals were
      assigned to trans (72%) and cis (28%) conformers. Crystallographic analysis of 4
      showed that only the cis conformation is present in the crystalline state. The
      (1)H NMR chemical shift pattern of three sets of signals observed in 2 was
      observed also in benzyl (2S)-1-[(2R/S)-3-methoxy-2-methyl-2-(4-methyl-2
      nitrophenoxy)-3-oxopropanoyl]-2-pyrrolidinecarboxylate. (R)-Carboxylic acid 5,
      after coupling with (S)-ProOBn, yielded benzyl (2S)-1-[(2R)-3-methoxy-2-methyl-2
      (4-methyl-2-nitrophenoxy)-3-oxopropanoyl]-2-pyrrolidinecarboxylate (6), which in
      DMSO-d(6) exhibited only the trans conformation of the proline peptide bond.
      These results suggest that in these particular cases acyl-Pro peptide bond
      isomerization is strongly influenced by the stereochemistry of the acyl residue
      preceding proline. (2S)-2,6-Dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2
      carboxylic acid (8) and (2R)-3-methoxy-2-methyl-2-(4-methyl-2-nitrophenoxy)-3
      oxopropanoic acid (5) are promising chiral peptidomimetic building blocks that
      can be used as acyl moieties to force the proline peptide bond into the trans
      conformation in a variety of acyl-Pro molecules.

PMID- 11597228
TI  - Electronic and steric control in regioselective addition reactions of
      organolithium reagents with enaldimines.
AB  - A reaction mode of imines derived from naphthalene-1-carbaldehyde and acyclic
      alpha,beta-unsaturated aldehydes with organolitium reagents was dependent on the
      characteristic nature of a substituent on the imine nitrogen atom. An imine
      having an electron-withdrawing aryl group on the nitrogen atom behaves as a 1,2
      directing imine toward organolithium reagents. In contrast, an imine bearing an
      alkyl or a bulky aryl group favors 1,4-addition of organolithium reagents.
      Electronic and steric tuning of a substituent on the imine nitrogen atom for a
      reaction mode was rationalized on the basis of molecular orbital calculations.

PMID- 11597229
TI  - The first synthesis and characterization of both diastereomers of a
      di[2.2]paracyclophane: 4,4'-bis(1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane).
AB  - The synthesis and characterization of both diastereomers of a system comprised of
      two [2.2]paracyclophane units linked through a single 4,4' bond are described.
      Both the meso and d,l diastereomers of 4,4'-bis(octafluoro[2.2]paracyclophane)
      have been prepared via a palladium-catalyzed reductive homocoupling reaction by
      copper, producing a 3:2 ratio of meso and d,l diastereomers. A similar reductive
      homocoupling of pseudo-o-iodotrifluoromethyloctafluoro[2.2]paracyclophane gave
      only the analogous meso diastereomer. Single-crystal X-ray structures were
      obtained for all of the diparacyclophane products.

PMID- 11597230
TI  - Extraannular fluorinated calixarenes: regiospecificity of the deoxofluorination
      reactions of bis(spirodienol) derivatives.
AB  - A new route for the partial displacement of OH groups of p-tert-butylcalixarene
      via spirodienol derivatives is described. NaBH(4) reduction of the
      bis(spirodienone) calixarene derivatives 2a-2c afforded the corresponding
      bis(spirodienols) 3a-3c in stereospecific fashion. (1)H NMR NOESY spectroscopy
      indicated that in the case of 2a, the reaction proceeds by attack at the exo face
      of the two carbonyls (the face located anti to the spiro C-O bond). The
      spirodienols readily revert to p-tert-butylcalix[4]arene when heated. The
      reaction of 3a with the deoxofluorinating agent DAST (Et(2)NSF(3)) afforded a
      mixture of extraannular substituted calixarenes possessing one or two fluoro
      substituted dehydroxylated rings. The bisfluorinated calixarene 6a adopts in the
      crystal a conformation (1,3-alternate) similar to that adopted in solution by the
      di-dehydroxylated calixarene 6b. An experiment conducted with a selectively
      deuterated spirodienol derivative indicated that the deoxofluorination reaction
      involves regiospecific nucleophilic attack at the gamma position of the
      pentadienol subunit.

PMID- 11597231
TI  - Self-sensitized photooxygenation of 3,4-dialkoxyfurans to vitamin C or its
      derivatives.
AB  - Self-sensitized photooxygenation of 3,4-dialkoxyfurans 3a-d with molecular oxygen
      and UV- or sunlight at room temperature gave vitamin C derivatives 2a-d in good
      to excellent yields. Furan 3c, having photodegradable protecting groups, was also
      photooxygenated to give L-ascorbic acid (1) in a "one-pot" reaction. Furthermore,
      a novel photolytic transformation was developed for deuteration of furan 3b at
      the C-2 position with D(2)O to give furan 3d in 95% yield. Toxicity of furans 3a
      c and butenolides 2a-c against human embryonic cell, murine embryo fibroblasts,
      normal fibroblasts, HeLa, and Vero cell lines in the presence of oxygen and
      indirect solar light was found to be much less than those of the antipsoriasis
      drugs anthralin and 8-methoxypsoralen.

PMID- 11597232
TI  - Quinone methide phosphodiester alkylations under aqueous conditions.
AB  - A detailed analysis of the alkylation of phosphodiesters with a p-quinone methide
      under aqueous conditions has been accomplished. The relative rates of
      phosphodiester alkylation and hydrolysis have been examined by (1)H NMR analysis
      of the reaction of 2,6-dimethyl-p-quinone methide in a buffered diethyl
      phosphate/acetonitrile solution (1:9 v/v, pH 4.0). The rate of hydrolysis of the
      quinone methide was confirmed by UV analysis in 28.5% solutions of aqueous
      inorganic phosphate in acetonitrile at pH 4.0 and 7.0. Similarly, the rate of
      phosphodiester alkylations by the quinone methide was also confirmed by UV
      analysis in 28.5% solutions of aqueous dibenzyl, dibutyl, or diethyl phosphate in
      acetonitrile at pH 4.0 and 7.0. These kinetic studies further establish that the
      phosphodiester alkylation reactions are acid-catalyzed, second-order processes.
      The rate constant for phosphodiester alkylation was found to range from
      approximately 370-3700 times the rate constant of quinone methide hydrolysis with
      diethyl and dibenzyl phosphate, respectively (pH 4.0, 28.5% aqueous
      acetonitrile).

PMID- 11597233
TI  - Enantiospecific synthesis of annulated nicotine analogues from D-glutamic acid. 7
      Azabicyclo[2.2.1]heptano[2.3-c]pyridines.
AB  - The conformationally restricted nicotinoid (1S,4S)-7-methyl-7
      azabicyclo[2.2.1]heptano[2,3-c]pyridine dihydrochloride has been prepared
      enantiospecifically from D-glutamic acid. The method involved a lithium cis-2,6
      dimethylpiperidide-mediated intramolecular anionic cyclization of (2S,5R)-N-(tert
      butyloxycarbonyl)-5-[3-(4-N-chloropyridinyl]proline methyl ester in tandem with a
      standard decarboxylation sequence. Reductive amination afforded the desired N
      methylated [2.2.1]bicyclonicotinoid. Cyclization of the corresponding
      iodopyridinylproline methyl ester, obtained via ultrasound-facilitated chloro
      iodo exchange, was also effected.

PMID- 11597234
TI  - How persistent is cyclopropyl upon nucleophilic substitution, and is frontside
      displacement possible? A model study.
AB  - Quantum chemical model calculations (MP2/6-31G(d,p)) demonstrate that frontside
      nucleophilic substitution is not possible in the reaction between water and
      protonated cyclopropanol. Instead, ring opening occurs, in accordance with a well
      known disrotary ring-opening mechanism. When the cyclopropane ring is embedded in
      a stabilizing bicyclic structure, as in protonated bicyclo[3.1.0]hexanol, the
      mechanistic landscape changes. In this case frontside nucleophilic substitution
      occurs, and has a potential energy barrier which is lower than that of the
      corresponding backside substitution, which implies that the stereochemical
      outcome of this gas-phase nucleophilic substitution reaction is uncoupled from
      its kinetic order. This and similar results challenge the traditional view that
      nucleophilic substitution reactions should be categorized as being either S(N)1
      or S(N)2.

PMID- 11597235
TI  - Synthesis and redox behavior of azulene-substituted benzene derivatives and
      (eta(5)-cyclopentadienyl)[tetra- and di(6-azulenyl)cyclobutadiene]cobalt
      complexes.
AB  - 1,2-Di(6-azulenyl)tetraphenylbenzenes and (6-azulenyl)pentaphenylbenzenes were
      synthesized by Diels-Alder reactions of di(6-azulenyl)acetylenes and 6
      (phenylethynyl)azulenes with tetraphenylcyclopentadienone. Cobalt-mediated
      cyclooligomerization of mono- and di(6-azulenyl)acetylenes afforded 1,3,5- and
      1,2,4-tri(6-azulenyl)benzene derivatives together with (eta(5)
      cyclopentadienyl)[tetra- and di(6-azulenyl)cyclobutadiene]cobalt complexes. The
      redox behavior of these novel (6-azulenyl)benzene derivatives and [tetra- and
      di(6-azulenyl)cyclobutadiene]cobalt complexes was examined by cyclic voltammetry
      (CV). Mono(6-azulenyl)benzenes exhibited a reduction wave upon CV. In contrast,
      1,2-di(6-azulenyl)benzenes showed a two-step reduction wave at the similar
      potential region upon CV, which revealed the formation of a dianion stabilized by
      6-azulenyl substituents under electrochemical reduction conditions. Three 6
      azulenyl substituents on benzene in a 1,2,4 relationship also increased electron
      accepting properties because of the formation of a closed-shell dianionic
      structure, whereas 1,3,5-tri(6-azulenyl)benzenes were reduced stepwise.

PMID- 11597236
TI  - An enantiospecific approach to tricyclic sesquiterpenes mayurone and thujopsenes.
AB  - An enantiospecific approach to mayurone and thujopsenes, sesquiterpenes
      containing three contiguous quaternary carbon atoms, starting from (R)-carvone
      (8), is described. (S)-3,4,4-Trimethylcarvone (7), obtained from (R)-carvone, was
      transformed into the bicyclo[2.2.2]octanone 13 via regioselective intramolecular
      alkylation of the allyl bromide 11. Regioselective ozonolysis and Criegee
      fragmentation of the bicyclic ketone 13 furnished the keto ester 14. Reductive
      deoxygenation followed by one-carbon homologation transformed the keto ester 19
      into the ester 6. Intramolecular cyclopropanation of the diazo ketone 25, derived
      from the acid 5, furnished (-)-dihydromayurone (4), thus constituting a formal
      enantiospecific synthesis of mayurone and thujopsenes.

PMID- 11597237
TI  - Total synthesis of (+/-)-stemodinone via an efficient ring-exchange strategy.
AB  - A total synthesis of (+/-)-stemodinone, a tetracyclic stemodane diterpene, from
      the known tricyclic methyl olefin 11 is described. The key steps involve an
      efficient ring-exchange reaction and palladium(0)-catalyzed lactone migration.
      The ring-exchange strategy for controlling the stereochemistry was based on an
      initial Diels-Alder reaction to form a new ring followed by cleavage of the
      original ring. Cleavage of the original ring of the Diels-Alder adduct 9 was
      achieved by an initial regio- and chemoselective Baeyer-Villiger oxidation
      followed by the Pd(0)-catalyzed lactone-migration reaction reported by us.

PMID- 11597238
TI  - Clean-chemistry synthesis of 2-tetralones in a single-stage acylation
      cycloalkylation process.
AB  - The preparation of substituted-2-tetralones by direct reaction of a 1-alkene with
      a substituted phenylacetic acid in a reaction system of trifluoroacetic anhydride
      (TFAA) and phosphoric acid is described. This single-stage process involves in
      situ formation of a mixed anhydride of the phenylacetic acid and acylation of the
      alkene by this species followed by cycloalkylation of the aromatic ring. This is
      a cleaner approach to the synthesis of 2-tetralones compared to Friedel-Crafts
      aliphatic acylation-cycloalkylation in that use of thionyl chloride, aluminum
      trichloride, and a chlorinated hydrocarbon solvent is eliminated. In addition,
      the atom efficiency is augmented by recovery of the spent TFAA as trifluoroacetic
      acid (TFA) and conversion of this back to TFAA by dehydration.

PMID- 11597240
TI  - Arylation of halogenated pyrimidines via a Suzuki coupling reaction.
AB  - The Suzuki coupling reaction has been used extensively for the synthesis of a
      wide variety of unsymmetrical biaryl compounds. We have extended this reaction to
      demonstrate the utility of preparing monophenyl-, diphenyl-, or
      triphenylpyrimidine depending on the reaction conditions. Further, it has been
      shown that chloropyrimidine substrates are preferable over iodo-, bromo-, or
      fluoropyrimidines.

PMID- 11597239
TI  - Sterically hindered C(alpha, alpha)-disubstituted alpha-amino acids: synthesis
      from alpha-nitroacetate and incorporation into peptides.
AB  - The preparation of sterically hindered and polyfunctional C(alpha,alpha)
      disubstituted alpha-amino acids (alpha alpha AAs) via alkylation of ethyl
      nitroacetate and transformation into derivatives ready for incorporation into
      peptides are described. Treatment of ethyl nitroacetate with N,N
      diisopropylethylamine (DIEA) in the presence of a catalytic amount of
      tetraalkylammonium salt, followed by the addition of an activated alkyl halide or
      Michael acceptor, gives the doubly C-alkylated product in good to excellent
      yields. Selective nitro reduction with Zn in acetic acid or hydrogen over Raney
      Ni gives the corresponding amino ester that, upon saponification, can be
      protected with the fluorenylmethyloxycarbonyl (Fmoc) group. The first synthesis
      of an orthogonally protected, tetrafunctional C(alpha,alpha)-disubstituted
      analogue of aspartic acid, 2,2-bis(tert-butylcarboxymethyl)glycine (Bcmg), is
      described. Also, the sterically demanding C(alpha,alpha)-dibenzylglycine (Dbg)
      has been incorporated into a peptide using solid-phase synthesis. It was found
      that once sterically congested Dbg is at the peptide N-terminus, further chain
      extension becomes very difficult using uronium or phosphonium salts (PyAOP,
      PyAOP/HOAt, HATU). However, preformed amino acid symmetrical anhydride couples to
      N-terminal Dbg in almost quantitative yield in nonpolar solvent (dichloroethane
      DMF, 9:1).

PMID- 11597242
TI  - Formation of cyclic ethers via the palladium-catalyzed cycloaddition of activated
      olefins with allylic carbonates having a hydroxy group at the terminus of the
      carbon chain.
AB  - The reaction of the activated olefins 1 with the allylic carbonate 2, having a
      hydroxy group at the terminus of the carbon chain, in the presence of catalytic
      amounts of Pd(2)dba(3).CHCl(3) and dppe in THF at room temperature gave the
      corresponding cycloaddition products, tetrahydrofuran derivatives 5, in good to
      very high yields. The diastereoselectivities (trans/cis ratios) of the products
      were in the range of ca. 60-70/40-30. The reaction of 1 with the hydroxy allylic
      carbonate 3 in the presence of catalytic amounts of Pd(2)dba(3).CHCl(3) and (o
      tolyl)(3)P in THF at 50 degrees C afforded the corresponding cycloaddition
      products, tetrahydropyran derivatives 6, in good to high yields. The trans/cis
      ratios of the products were in the range of ca. 0-40/99-80. The reaction of 1a
      with the hydroxy allylic carbonate 4 needed higher reaction temperatures
      (approximately 100 degrees C) to give the cycloaddition product, the oxepane 7a,
      in 31% yield with low diastereoselectivity. Next, catalytic asymmetric syntheses
      of tetrahydrofuran and -pyran derivatives were carried out. With the Trost ligand
      15, good to high ees were accomplished in the cycloaddition, although the
      diastereoselectivities were of low level. With the Hayashi ligand 16, good to
      high ees were also achieved in the cycloaddition. The absolute stereochemistries
      of the major enantiomers of 5l, 5m, and 6d were determined unambiguously by X-ray
      crystallographic analysis: trans-(2R,4R)-5l, cis-(2S,4R)-5l, 4R-5m, trans-(2S,4S)
      6d, and cis-(2R,4S)-6d were major enantiomers. Based upon the absolute
      stereochemistries of the major enantiomers, the mechanism of catalytic asymmetric
      induction in the cycloaddition reaction is discussed.

PMID- 11597241
TI  - Design, synthesis, and bioactivity of the first nonsteroidal mimetics of
      brassinolide.
AB  - Ten novel compounds, each consisting of two subunits and a linker, were designed
      with the aid of molecular modeling to resemble the natural steroidal phytohormone
      brassinolide. The mimetics were synthesized and subjected to the rice leaf lamina
      inclination bioassay to test for brassinosteroid activity. Most of the mimetics
      displayed very weak or no bioactivity, but two were strongly active when
      coapplied with the auxin indole-3-acetic acid (IAA), which synergizes the
      activity of brassinosteroids. Thus, 1-(4,6 alpha,7 alpha-trihydroxy-5,6,7,8
      tetrahydronaphthyl)-2-(6 alpha',7 alpha'-dihydroxy-5',6',7',8'
      tetrahydronaphthyl)ethyne (4) and (E)-1,2-bis[trans-(4a alpha,8a beta)-4-oxo-6
      alpha,7 alpha-dihydroxy-4a,5,6,7,8,8a-hexahydro-(3H)-naphthyl]ethylene (11)
      showed exceptional activity at doses as low as 0.01 ng and 0.001 ng/plant,
      respectively. These compounds are the first biologically active nonsteroidal
      brassinolide mimetics.

PMID- 11597243
TI  - Bromo-boronolactonization of olefins.
AB  - Exposure of a variety of mono- and disubstituted ortho-alkenylarylboronic acids
      to NBS in THF/H(2)O under neutral conditions affords bromo-boronolactones, in
      some instances, with exceptional regiocontrol. The adducts, analogous to those
      formed by carboxylic acids, are shown to be useful synthetic intermediates.

PMID- 11597244
TI  - Template-free segmental synthesis of oligonucleotides containing nonnative
      linkages.
AB  - Protected oligonucleotides containing 3'-alkyl carboxylic acids or 3'-alkylamines
      were obtained from photolabile solid-phase synthesis supports (1 and 4).
      Protected oligonucleotides containing 5'-alkylamines and 3'-hydroxyl groups were
      obtained using a photolabile solid-phase synthesis support (2) and a commercially
      available phosphoramidite reagent (3). Depending upon the source of alkylamine
      containing oligonucleotide, the segments were coupled under mild conditions to
      form products containing either 5'-3' or 3'-3' linkages in good yield and high
      purity. Oligonucleotides as long as 40 nucleotides were prepared, and coupling
      yields of protected biopolymer segments were independent of length over the range
      examined. This method is particularly well suited for the convergent synthesis of
      oligonucleotides containing nonnative linkages and should be useful for the rapid
      assembly of modified biopolymers that are useful in biochemical studies.

PMID- 11597245
TI  - Formation of macrocycles via ring-closing olefin metathesis.
AB  - The enhanced metathesis activity of 1,3-dimesityl-4,5-dihydroimidazole-2-ylidene
      ruthenium carbene catalyst 3 significantly increases the feasibility of
      synthesizing macrocyclic compounds. Catalyst 3 exhibits sufficient activity in
      RCM to dimerize alpha,beta-unsaturated ester substrates and afford the
      corresponding head-to-tail (E,E)-dimeric (and trimeric) macrocycles. The
      dimerization appears to be under thermodynamic control with the product mixture
      dependent not only on the electronic and steric nature of the substrate but also
      on concentration.

PMID- 11597246
TI  - Palladium-catalyzed arylation of allylic benzoates using hypervalent siloxane
      derivatives.
AB  - Palladium-catalyzed cross-coupling of hypervalent arylsiloxane derivatives
      proceeded in good to excellent yields with allylic benzoates. Arylation occurred
      with complete inversion of configuration. The scope and limitations of this
      reaction, an alternative to the Stille coupling, is summarized.

PMID- 11597247
TI  - Dynamic equilibria in the products of intramolecular Buchner additions of
      diazoketones to aryl rings bearing methoxy substituents.
AB  - Rhodium carboxylate catalyzed aromatic addition reactions of a range of
      diazoketones bearing methoxy-substituted aryl rings have been explored. While the
      existence of norcaradiene-cycloheptatriene equilibria in related compounds is
      well established, the aromatic addition products in this study display more
      complex dynamic equilibria due to conjugation with the methoxy group; the
      experimental evidence for this is discussed in detail. In the azulenone products
      21-26 derived from p-methoxy-substituted diazoketones 14-16, the diastereomers
      interconvert via a spiro intermediate 39. A related mechanistic process in the
      azulenones 43-46 derived from the o-methoxy-substituted diazoketones 17, 18
      interconverts regioisomers, explaining the conflicting reports for the
      regioselectivity of the cyclization of diazoketone 1. With the m-methoxy
      substituted diazoketone 19, involvement of the methoxy group through a different
      pathway results in fragmentation of the azulenone to form the tetralone 47. With
      the azulenones 21-26 exclusive trapping of the norcaradiene associated with the
      less thermodynamically stable diastereomers in a cycloadduct with N
      phenylmaleimide is observed. Due to the presence of the activating methoxy
      substituent on the aromatic ring, the aromatic addition reactions of the
      diazoketones studied were not very sensitive to the nature of the rhodium
      catalyst.

PMID- 11597248
TI  - Lipo alpha-amino-beta-hydroxy acids and O-linked glycosides: building blocks for
      ceramyl and glycosphingoyl peptides.

PMID- 11597249
TI  - A new synthesis of valienamine.

PMID- 11597250
TI  - A two-step procedure for the conversion of alpha,beta-unsaturated aldehydes into
      gamma-azido-alpha,beta-unsaturated nitriles.

PMID- 11597251
TI  - Reactivity of alpha-(benzoyloxy)crotylstannane with aldehydes in liquid phase and
      on solid support. Synthesis of substituted lactones.

PMID- 11597252
TI  - Preparation of a (+/-)-1,6-di-O-feruloyl-myo-inositol derivative: an efficient
      method for introduction of ferulic acid to 1,6-vicinal hydroxyl groups of myo
      inositol.

PMID- 11597253
TI  - Reaction of 1,3-bis(alkylseleno)allenes with diphenyl diazomethane.

PMID- 11597254
TI  - Stereoselective synthesis of bridged azepine derivatives via polyfunctionalized
      spiroannulated thiophene. Novel rearrangement of oxime esters.

PMID- 11597256
TI  - A new C-F bond-cleavage route for the synthesis of octafluoro[2.2]paracyclophane.

PMID- 11597255
TI  - Cooperative multiple recognition by novel calix[4]arene-tethered beta
      cyclodextrin and calix[4]arene-bridged bis(beta-cyclodextrin).

PMID- 11597257
TI  - Novel intramolecular rearrangement of tertiary propargylamine N-oxides.

PMID- 11597258
TI  - Regioselective asymmetric aminohydroxylation approach to a beta
      hydroxyphenylalanine derivative for the synthesis of ustiloxin D.

PMID- 11597259
TI  - Polar-pi and cation-pi stabilizing interactions between constrained cofacial
      aromatic rings favoring the more sterically hindered diastereomer.

PMID- 11597260
TI  - Stereocontrolled synthesis of unsaturated halohydrins from unsaturated epoxides.

PMID- 11597265
TI  - Medical, mental health communities mobilize to cope with terror's psychological
      aftermath.

PMID- 11597266
TI  - HIV vaccine efforts inch forward.

PMID- 11597271
TI  - Medical research in the 21st century.

PMID- 11597272
TI  - Medical research in the 21st century.

PMID- 11597273
TI  - Medical research in the 21st century.

PMID- 11597274
TI  - Medical research in the 21st century.

PMID- 11597277
TI  - Early childhood educational intervention and long-term developmental outcomes.

PMID- 11597279
TI  - Ipriflavone and osteoporosis.

PMID- 11597281
TI  - Economic consequences of collective bargaining by physicians.

PMID- 11597282
TI  - Economic consequences of collective bargaining by physicians.

PMID- 11597284
TI  - Coding changes and apparent HIV/AIDS mortality trends in Florida, 1999.

PMID- 11597285
TI  - The Canadian C-spine rule for radiography in alert and stable trauma patients.
AB  - CONTEXT: High levels of variation and inefficiency exist in current clinical
      practice regarding use of cervical spine (C-spine) radiography in alert and
      stable trauma patients. OBJECTIVE: To derive a clinical decision rule that is
      highly sensitive for detecting acute C-spine injury and will allow emergency
      department (ED) physicians to be more selective in use of radiography in alert
      and stable trauma patients. DESIGN: Prospective cohort study conducted from
      October 1996 to April 1999, in which physicians evaluated patients for 20
      standardized clinical findings prior to radiography. In some cases, a second
      physician performed independent interobserver assessments. SETTING: Ten EDs in
      large Canadian community and university hospitals. PATIENTS: Convenience sample
      of 8924 adults (mean age, 37 years) who presented to the ED with blunt trauma to
      the head/neck, stable vital signs, and a Glasgow Coma Scale score of 15. MAIN
      OUTCOME MEASURE: Clinically important C-spine injury, evaluated by plain
      radiography, computed tomography, and a structured follow-up telephone interview.
      The clinical decision rule was derived using the kappa coefficient, logistic
      regression analysis, and chi(2) recursive partitioning techniques. RESULTS: Among
      the study sample, 151 (1.7%) had important C-spine injury. The resultant model
      and final Canadian C-Spine Rule comprises 3 main questions: (1) is there any high
      risk factor present that mandates radiography (ie, age >/=65 years, dangerous
      mechanism, or paresthesias in extremities)? (2) is there any low-risk factor
      present that allows safe assessment of range of motion (ie, simple rear-end motor
      vehicle collision, sitting position in ED, ambulatory at any time since injury,
      delayed onset of neck pain, or absence of midline C-spine tenderness)? and (3) is
      the patient able to actively rotate neck 45 degrees to the left and right? By
      cross-validation, this rule had 100% sensitivity (95% confidence interval [CI],
      98%-100%) and 42.5% specificity (95% CI, 40%-44%) for identifying 151 clinically
      important C-spine injuries. The potential radiography ordering rate would be
      58.2%. CONCLUSION: We have derived the Canadian C-Spine Rule, a highly sensitive
      decision rule for use of C-spine radiography in alert and stable trauma patients.
      If prospectively validated in other cohorts, this rule has the potential to
      significantly reduce practice variation and inefficiency in ED use of C-spine
      radiography.

PMID- 11597286
TI  - Impact of first-line vs second-line antibiotics for the treatment of acute
      uncomplicated sinusitis.
AB  - CONTEXT: Studies suggest little benefit in relief of acute sinusitis symptoms
      from the use of newer and more expensive (second-line) antibiotics instead of
      older and less expensive (first-line) antibiotics. However, researchers have
      failed to include development of complications and cost of care in their
      analyses. OBJECTIVE: To compare the effectiveness and cost of first-line with
      second-line antibiotics for the treatment of acute uncomplicated sinusitis in
      adults. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study using a
      pharmaceutical database containing demographic, clinical (International
      Classification of Diseases, Ninth Revision), treatment, and charge information
      for 29 102 adults with a diagnosis of acute sinusitis receiving initial
      antibiotic treatment between July 1, 1996, and June 30, 1997. MAIN OUTCOME
      MEASURES: Absence of additional claim for an antibiotic in the 28 days after the
      initial antibiotic, presence of a claim for a second antibiotic, serious
      complications of sinusitis, and direct charges and use for the acute sinusitis
      treatment. RESULTS: There were 17 different antibiotics prescribed in this study.
      The majority (59.5%) of patients received 1 of the first-line antibiotics. The
      overall success rate was 90.4% (95% confidence interval [CI], 90.0%-90.8%). The
      success rate for the 17 329 patients who received a first-line antibiotic was
      90.1% and for the 11 773 patients who received a second-line antibiotic was
      90.8%, a difference of 0.7% (95% CI, 0.01%-1.40%; P<.05). There were 2 cases of
      periorbital cellulitis, one in each treatment group. The average total direct
      charge for patients receiving a first-line antibiotic was $68.98 and a second
      line antibiotic was $135.17, a difference of $66.19 (95% CI, $64.95-$67.43;
      P<.001). This difference was due entirely to the difference in charge of
      antibiotics and not other charges, such as professional fees, laboratory tests,
      or emergency department visits. CONCLUSIONS: Patients treated with a first-line
      antibiotic for acute uncomplicated sinusitis did not have clinically significant
      differences in outcomes vs those treated with a second-line antibiotic. However,
      cost of care was significantly higher for patients treated with a second-line
      antibiotic.

PMID- 11597287
TI  - Macrolide resistance among invasive Streptococcus pneumoniae isolates.
AB  - CONTEXT: Macrolide antibiotics, including erythromycin, clarithromycin, and
      azithromycin, are the mainstays of empirical pneumonia therapy. Macrolide
      resistance among Streptococcus pneumoniae, the most common cause of community
      acquired pneumonia, is increasing in the United States. Whether resistance is a
      significant problem or whether macrolides remain useful for treatment of most
      resistant strains is unknown. OBJECTIVE: To examine the epidemiology of macrolide
      resistant pneumococci in the United States. DESIGN AND SETTING: Analysis of 15
      481 invasive isolates from 1995 to 1999 collected by the Centers for Disease
      Control and Prevention's Active Bacterial Core surveillance system in 8 states.
      MAIN OUTCOME MEASURES: Trends in macrolide use (1993-1999) and resistance and
      factors associated with resistance, including examination of 2 subtypes, the M
      phenotype, associated with moderate minimum inhibitory concentrations (MICs), and
      the MLS(B) phenotype, associated with high MICs and clindamycin resistance.
      RESULTS: From 1993 to 1999, macrolide use increased 13%; macrolide use increased
      320% among children younger than 5 years. Macrolide resistance increased from
      10.6% in 1995 to 20.4% in 1999. M phenotype isolates increased from 7.4% to 16.5%
      (P<.001), while the proportion with the MLS(B) phenotype was stable (3%-4%). The
      median erythromycin MIC (MIC(50)) of M phenotype isolates increased from 4
      microg/mL to 8 microg/mL. In 1999, M phenotype strains were more often from
      children than persons 5 years or older (25.2% vs 12.6%; P<.001) and from whites
      than blacks (19.3% vs 11.2%; P<.001). CONCLUSIONS: In the setting of increasing
      macrolide use, pneumococcal resistance has become common. Most resistant strains
      have MICs in the range in which treatment failures have been reported. Further
      study and surveillance are critical to understanding the clinical implications of
      our findings.

PMID- 11597288
TI  - Fetal deaths related to maternal injury.
AB  - CONTEXT: Maternal and fetal trauma is an important cause of adverse fetal
      outcomes. However, systematic exclusion from US injury surveillance programs of
      even the most severe outcome, fetal/neonatal death, has led to a lack of
      understanding about frequency, causes, and prevention. OBJECTIVE: To determine
      the rate of traumatic fetal deaths reported in state fetal death registries and
      the types of trauma and physiologic diagnoses associated with these deaths.
      DESIGN AND SETTING: Retrospective descriptive study of fetal death certificates
      from 1995 through 1997 obtained from 16 states, which accounted for 55% of US
      live births and approximately 15 000 fetal death registrations per year. MAIN
      OUTCOME MEASURE: Rate of fetal injury deaths, based on fetal death certificates
      coded with an underlying cause of death due to maternal injury at 20 weeks'
      gestation or later, by cause. RESULTS: During the 3-year study period, 240
      traumatic fetal injury deaths were identified (3.7 fetal deaths per 100 000 live
      births). Motor vehicle crashes were the leading trauma mechanism (82% of cases;
      2.3 fetal deaths per 100 000 live births), followed by firearm injuries (6% of
      cases) and falls (3% of cases). In 3 states, reported crash-related fetal deaths
      exceeded that of crash-related infant deaths. Placental injury was mentioned in
      100 cases (42%) and maternal death was noted in 27 cases (11%). A peak rate of
      9.3 fetal deaths per 100 000 live births was observed among 15- to 19-year-old
      women. CONCLUSIONS: Motor vehicle crashes are the leading cause of fetal deaths
      related to maternal trauma. Improved tracking of traumatic fetal injury deaths is
      important to stimulate and guide research and efforts to reduce the risks to
      women and fetuses from injury during pregnancy.

PMID- 11597289
TI  - Caring for the critically ill patient. High-dose antithrombin III in severe
      sepsis: a randomized controlled trial.
AB  - CONTEXT: Activation of the coagulation system and depletion of endogenous
      anticoagulants are frequently found in patients with severe sepsis and septic
      shock. Diffuse microthrombus formation may induce organ dysfunction and lead to
      excess mortality in septic shock. Antithrombin III may provide protection from
      multiorgan failure and improve survival in severely ill patients. OBJECTIVE: To
      determine if high-dose antithrombin III (administered within 6 hours of onset)
      would provide a survival advantage in patients with severe sepsis and septic
      shock. DESIGN AND SETTING: Double-blind, placebo-controlled, multicenter phase 3
      clinical trial in patients with severe sepsis (the KyberSept Trial) was conducted
      from March 1997 through January 2000. PATIENTS: A total of 2314 adult patients
      were randomized into 2 equal groups of 1157 to receive either intravenous
      antithrombin III (30 000 IU in total over 4 days) or a placebo (1% human
      albumin). MAIN OUTCOME MEASURE: All-cause mortality 28 days after initiation of
      study medication. RESULTS: Overall mortality at 28 days in the antithrombin III
      treatment group was 38.9% vs 38.7% in the placebo group (P =.94). Secondary end
      points, including mortality at 56 and 90 days and survival time in the intensive
      care unit, did not differ between the antithrombin III and placebo groups. In the
      subgroup of patients who did not receive concomitant heparin during the 4-day
      treatment phase (n = 698), the 28-day mortality was nonsignificantly lower in the
      antithrombin III group (37.8%) than in the placebo group (43.6%) (P =.08). This
      trend became significant after 90 days (n = 686; 44.9% for antithrombin III group
      vs 52.5% for placebo group; P =.03). In patients receiving antithrombin III and
      concomitant heparin, a significantly increased bleeding incidence was observed
      (23.8% for antithrombin III group vs 13.5% for placebo group; P<.001).
      CONCLUSIONS: High-dose antithrombin III therapy had no effect on 28-day all-cause
      mortality in adult patients with severe sepsis and septic shock when administered
      within 6 hours after the onset. High-dose antithrombin III was associated with an
      increased risk of hemorrhage when administered with heparin. There was some
      evidence to suggest a treatment benefit of antithrombin III in the subgroup of
      patients not receiving concomitant heparin.

PMID- 11597290
TI  - Meningiomas in lymphangioleiomyomatosis.
AB  - CONTEXT: Lymphangioleiomyomatosis (LAM), a cystic lung disease associated with
      progressive respiratory failure, is found predominantly in women of childbearing
      age and therefore has been treated with progesterone and other hormonal agents.
      However, meningiomas have progesterone receptors, and progesterone is believed to
      be a mitogen for meningioma cells in culture. Since 30% to 40% of patients with
      tuberous sclerosis complex (TSC) have LAM, we routinely screen patients with LAM
      for brain lesions found in TSC. OBJECTIVE: To determine the prevalence of
      meningiomas in women with LAM. DESIGN AND SETTING: Analysis of results from
      ongoing routine screening protocols initiated in December 1995 at the National
      Heart, Lung, and Blood Institute. PATIENTS: Two hundred fifty women with sporadic
      LAM who were referred for screening by magnetic resonance imaging (MRI) and/or
      computed tomography (CT) of the brain. MAIN OUTCOME MEASURES: Presence of
      meningiomas on MRI and/or CT scans. RESULTS: Eight women with LAM (3 with and 5
      without a diagnosis of TSC) had lesions on MRI scans compatible with meningiomas.
      Five of the patients had been treated with progesterone. Multiple meningiomas
      were observed in 2 patients. CONCLUSIONS: Women with LAM appear to have a high
      prevalence of meningiomas. We recommend that patients with LAM be screened for
      meningiomas regardless of diagnosis of TSC. In view of the lack of a documented
      effect of progesterone on progression of lung disease in LAM and the reported
      mitogenic response of meningiomas to progesterone, we recommend that the drug not
      be given to LAM patients with an MRI result consistent with diagnosis of
      meningioma.

PMID- 11597291
TI  - Ramipril and the development of diabetes.
AB  - CONTEXT: Type 2 diabetes is a growing clinical and public health problem.
      Preventive efforts related to lifestyle modification are not always successful;
      therefore, alternative prevention strategies need to be studied. OBJECTIVE: To
      investigate the effectiveness of ramipril, an angiotensin-converting enzyme
      inhibitor, in preventing diabetes among high-risk persons. DESIGN, SETTING, AND
      PARTICIPANTS: The randomized, controlled Heart Outcomes Prevention Evaluation
      trial of 5720 patients older than 55 years without known diabetes but with
      vascular disease who were followed up for a mean of 4.5 years. The study included
      267 hospitals in 19 countries and was conducted between 1994 and 1999.
      INTERVENTION: Patients were randomly assigned to receive ramipril, up to 10 mg/d
      (n = 2837), or placebo (n = 2883). MAIN OUTCOME MEASURE: Diagnosis of diabetes
      determined from self-report at follow-up visits every 6 months, compared between
      the 2 groups. RESULTS: One hundred and two individuals (3.6%) in the ramipril
      group developed diabetes compared with 155 (5.4%) in the placebo group (relative
      risk [RR], 0.66; 95% confidence interval [CI], 0.51-0.85, P<.001). Similar
      results were noted when different diagnostic criteria were used; in the ramipril
      group, the RR for diagnosis of diabetes and hemoglobin A(1c) greater than 110%
      was 0.60 (95% CI, 0.43-0.85), for initiation of glucose-lowering therapy, 0.56
      (95% CI, 0.41-0.77), and for both, 0.51 (95% CI, 0.34-0.76). These effects were
      also consistently seen in several subgroups examined. CONCLUSIONS: Ramipril is
      associated with lower rates of new diagnosis of diabetes in high-risk
      individuals. Because these results have important clinical and public health
      implications, this hypothesis requires prospective confirmation.

PMID- 11597292
TI  - Do patents for antiretroviral drugs constrain access to AIDS treatment in Africa?
AB  - Public attention and debate recently have focused on access to treatment of
      acquired immunodeficiency syndrome (AIDS) in poor, severely affected countries,
      such as those in Africa. Whether patents on antiretroviral drugs in Africa are
      impeding access to lifesaving treatment for the 25 million Africans with human
      immunodeficiency virus infection is unknown. We studied the patent statuses of 15
      antiretroviral drugs in 53 African countries. Using a survey method, we found
      that these antiretroviral drugs are patented in few African countries (median, 3;
      mode, 0) and that in countries where antiretroviral drug patents exist, generally
      only a small subset of antiretroviral drugs are patented (median and mode, 4).
      The observed scarcity of patents cannot be simply explained by a lack of patent
      laws because most African countries have offered patent protection for
      pharmaceuticals for many years. Furthermore, in this particular case, geographic
      patent coverage does not appear to correlate with antiretroviral treatment access
      in Africa, suggesting that patents and patent law are not a major barrier to
      treatment access in and of themselves. We conclude that a variety of de facto
      barriers are more responsible for impeding access to antiretroviral treatment,
      including but not limited to the poverty of African countries, the high cost of
      antiretroviral treatment, national regulatory requirements for medicines, tariffs
      and sales taxes, and, above all, a lack of sufficient international financial aid
      to fund antiretroviral treatment. We consider these findings in light of policies
      for enhancing antiretroviral treatment access in poor countries.

PMID- 11597293
TI  - Identifying patients at low risk for cervical spine injury: the Canadian C-spine
      rule for radiography.

PMID- 11597294
TI  - Continuing challenges of sepsis research.

PMID- 11597295
TI  - The patient-physician relationship. Narrative medicine: a model for empathy,
      reflection, profession, and trust.
AB  - The effective practice of medicine requires narrative competence, that is, the
      ability to acknowledge, absorb, interpret, and act on the stories and plights of
      others. Medicine practiced with narrative competence, called narrative medicine,
      is proposed as a model for humane and effective medical practice. Adopting
      methods such as close reading of literature and reflective writing allows
      narrative medicine to examine and illuminate 4 of medicine's central narrative
      situations: physician and patient, physician and self, physician and colleagues,
      and physicians and society. With narrative competence, physicians can reach and
      join their patients in illness, recognize their own personal journeys through
      medicine, acknowledge kinship with and duties toward other health care
      professionals, and inaugurate consequential discourse with the public about
      health care. By bridging the divides that separate physicians from patients,
      themselves, colleagues, and society, narrative medicine offers fresh
      opportunities for respectful, empathic, and nourishing medical care.

PMID- 11597300
TI  - Windows in early mammary development: critical or not?
AB  - Two critical windows in mammary development have been proposed. The first arises
      from observations in rodents that nutrition during fetal and neonatal periods can
      affect mammary ductular outgrowth, subsequent proliferative activity and,
      eventually, tumorigenesis, that is, potentially it could have a long-term effect
      on pathological outcome (breast cancer) in women. The second similarly involves
      early diet, but in this case the outcome is phenotypic, in that dairy heifers
      reared too quickly during the peripubertal period subsequently show impaired
      udder development and reduced milk yield persisting throughout life. Most mammary
      development occurs during pregnancy, but this period is usually thought of only
      in terms of the immediate outcome for the subsequent lactation; it is not
      believed to be a critical window, at least in terms of lifetime mammary
      productivity. This review examines the evidence underlying these various claims
      and attempts to define the mechanisms involved, and also considers whether
      derangements occurring earlier in life (prenatally) could also have long-term
      consequences for physiological or pathological mammary development.

PMID- 11597301
TI  - Nutrient partitioning during adolescent pregnancy.
AB  - Human adolescent mothers have an increased risk of delivering low birth weight
      and premature infants with high mortality rates within the first year of life.
      Studies using a highly controlled adolescent sheep paradigm demonstrate that, in
      young growing females, the hierarchy of nutrient partitioning during pregnancy is
      altered to promote growth of the maternal body at the expense of the gradually
      evolving nutrient requirements of the gravid uterus and mammary gland. Thus,
      overnourishing adolescent dams throughout pregnancy results in a major
      restriction in placental mass, and leads to a significant decrease in birth
      weight relative to adolescent dams receiving a moderate nutrient intake. High
      maternal intakes are also associated with increased rates of spontaneous abortion
      in late gestation and, for ewes delivering live young, with a reduction in the
      duration of gestation and in the quality and quantity of colostrum accumulated
      prenatally. As the adolescent dams are of equivalent age at the time of
      conception, these studies indicate that nutritional status during pregnancy
      rather than biological immaturity predisposes the rapidly growing adolescents to
      adverse pregnancy outcome. Nutrient partitioning between the maternal body and
      gravid uterus is putatively orchestrated by a number of endocrine hormones and,
      in this review, the roles of both maternal and placental hormones in the
      regulation of placental and fetal growth in this intriguing adolescent paradigm
      are discussed. Impaired placental growth, particularly of the fetal component of
      the placenta, is the primary constraint to fetal growth during late gestation in
      the overnourished dams and nutritional switch-over studies indicate that high
      nutrient intakes during the second two-thirds of pregnancy are most detrimental
      to pregnancy outcome. In addition, it may be possible to alter the nutrient
      transport function of the growth-restricted placenta in that the imposition of a
      catabolic phase during the final third of pregnancy in previously rapidly growing
      dams results in a modest increase in lamb birth weight.

PMID- 11597302
TI  - Impact of manipulations of myogenesis in utero on the performance of adult
      skeletal muscle.
AB  - The possibility that early fetal programming affects health or disease status in
      adult life has been considered in relation to tissues such as the cardiovascular
      system but not with respect to skeletal muscle. Since muscle mass and function
      are important for life, it is pertinent to ask whether events during the
      development of muscle in utero can affect the performance of the tissue in later
      life. This review discusses the factors that influence muscle performance,
      outlines the current understanding of myogenesis and examines how manipulations
      alter myogenic outcome after birth. The performance of muscle is determined by
      the number, type and size of the muscle fibres, these in turn being affected by a
      number of factors, and the evidence indicates that the proportions of types of
      muscle fibre have a heritable component. The formation of muscle occurs early in
      embryogenesis and it appears that the major impacts on myogenesis are associated
      with extremes of treatment or embryo manipulations. The impact of extremes of
      treatment or embryo manipulations on myogenesis is seen in the secondary fibres
      whereas primary fibres appear to be insensitive or protected. Overall, the
      opportunities for manipulation of myogenesis in utero to improve adult
      performance are limited.

PMID- 11597303
TI  - Influence of placentally mediated fetal growth restriction on the onset of
      puberty in male and female lambs.
AB  - The onset of puberty in prenatally growth-restricted versus normally grown lambs
      of both sexes, born in April and housed under natural photoperiod, was examined.
      Singleton pregnancies were established and adolescent ewes were offered a high or
      moderate nutrient intake throughout gestation. Placental mass was reduced (P <
      0.001) in high compared with moderate intake dams and resulted in the birth of
      growth-restricted and normal birth weight offspring, respectively. At birth,
      female lambs weighed 3.43 kg versus 5.03 kg (P < 0.001; n = 14 per group) and
      male lambs weighed 2.75 kg versus 5.18 kg (P < 0.001; n = 7 per group) in growth
      restricted and normal birth weight groups, respectively. Lambs suckled for 12
      weeks and thereafter were fed ad libitum until week 43 of age. Growth-restricted
      lambs had lower preweaning live weight gains and this difference was more
      pronounced in male (P < 0.05) than in female lambs (P = 0.07). Thereafter, live
      weight remained lower (P < 0.05) in growth-restricted than in normally grown
      lambs of both sexes until week 25 of age. In females, the time of onset of
      puberty was similar in the two groups. All females ovulated and there were no
      differences in the number of ovarian cycles recorded or in the incidence of
      aberrant ovarian function. In males, testosterone concentrations and testicular
      volume were lower in growth-restricted compared with normally developed lambs
      from birth until weeks 28 and 35 of age, respectively (P < 0.05). The seasonal
      increase in plasma testosterone concentrations occurred later in growth
      restricted than in normally developed lambs (P < 0.01) but the timing of maximum
      peak concentrations was similar. Peak testosterone concentrations were lower (P <
      0.05) in growth-restricted than in normal male lambs.

PMID- 11597304
TI  - Gender differences in the inhibitory effects of a reduction in ambient
      temperature and a reduction in food quantity on reproduction in the Southern
      African rodent, Rhabdomys pumilio.
AB  - The effects of a reduction in ambient temperature (from 26 degrees C to 15
      degrees C) and a 10% reduction in daily food consumption on reproductively active
      male and female four-striped field mice ( Rhabdomys pumilio) were investigated.
      In male R. pumilio, both reduced ambient temperature and a reduction in food
      quantity had an inhibitory effect on spermatogenesis and on size of the
      reproductive organs, and this was greatest when the two factors were combined and
      the effect of fat was removed. Female R. pumilio responded differently and
      reproduction was inhibited by a reduction in food quantity, irrespective of
      ambient temperature. The masses of the ovaries and uterus, the numbers of
      developing follicles and corpora lutea, and the development of the uterine wall
      were all reduced by food deprivation at 26 degrees C to levels similar to those
      that resulted from a reduction in ambient temperature to 15 degrees C with a
      reduction in food quantity. It is concluded that reproduction in R. pumilio from
      the Eastern Cape Province of South Africa is opportunistic, that reproduction
      will be inhibited by an energetic challenge and that there is sexual dimorphism
      in the response to ambient temperature and food supply.

PMID- 11597305
TI  - Inter-relationships among gonadotrophins, reproductive steroids and inhibin in
      freemartin ewes.
AB  - Freemartins are sterile XX/XY chimaeras that occur as a result of placental
      fusion between male and female fetuses during early pregnancy. Freemartins occur
      predominantly in cattle, although the prevalence of ovine freemartinism is
      increasing. In this study, the reproductive endocrinology of ovine freemartins
      was compared with that of normal sheep. Freemartins had significantly (P < 0.001)
      higher basal concentrations of LH and FSH than did normal ewes or rams, although
      the response of LH to GnRH (10 microg) was similar in freemartins, ewes and rams.
      Resting concentrations of oestradiol were similar in freemartins and ewes and
      were increased in both after eCG administration. Testosterone concentrations were
      higher in freemartins than in ewes, but were unresponsive to GnRH or eCG.
      Administration of 62.5 mg progesterone or 25 lg oestradiol twice a day for 3 days
      suppressed LH concentrations to baseline values in freemartins, ewes and rams. In
      ewes, 500 microg oestradiol administered twice a day caused preovulatory surges
      in LH concentrations, but suppressed LH in freemartins to baseline values. Thus,
      LH secretion can potentially be regulated in freemartins by gonadal steroids. FSH
      concentrations in freemartins were not suppressed by doses of inhibin that were
      effective in ewes and rams. Therefore, freemartins behave in part like castrated
      animals, as they have high basal concentrations of LH and FSH, which can be
      stimulated by GnRH and suppressed by gonadal steroids. Conversely, inhibin does
      not suppress FSH concentrations in freemartins, and freemartins have circulating
      concentrations of steroids intermediate between those of castrated and normal
      animals.

PMID- 11597306
TI  - Comparison of androgen receptor and oestrogen receptor beta immunoexpression in
      the testes of the common marmoset (Callithrix jacchus) from birth to adulthood:
      low androgen receptor immunoexpression in Sertoli cells during the neonatal
      increase in testosterone concentrations.
AB  - The aims of this study were: (i) to investigate the cellular immunoexpression of
      androgen receptor and oestrogen receptor beta in the testes of the common
      marmoset (Callithrix jacchus) during neonatal life compared with their expression
      at later ages; (ii) to establish whether neonatal marmoset Sertoli cells are
      targets for androgens or oestrogens or both; and (iii) to investigate the
      relationship between neonatal plasma testosterone concentrations and androgen
      receptor immunoexpression by abolishing the neonatal testosterone surge with a
      potent GnRH antagonist. Androgen receptor and oestrogen receptor beta
      immunoexpression were evaluated in neonatal animals aged 1-4 days, 4 weeks and 6
      weeks, and compared with immunoexpression in animals aged 18-22 weeks (early
      infancy), 35 weeks (late infancy), 58-62 weeks (late pubertal) and > 100 weeks
      (adult). Immunoexpression of androgen receptor in the reproductive tract was also
      evaluated at each age. Sertoli cell immunoexpression of androgen receptor was
      weak or absent in neonatal animals, but increased substantially in infant
      animals, reaching adult levels by the end of infancy. In contrast,
      immunoexpression of androgen receptor during the neonatal period was strong in
      testicular interstitial cells and very strong in epithelial cell nuclei
      throughout the reproductive tract, and did not change greatly with age in these
      cells or tissues. Similarly, immunoexpression of oestrogen receptor beta was
      prominent in many Sertoli cells and in the germ cells of neonatal animals, and
      was relatively constant throughout life. Weak immunoexpression of androgen
      receptor in neonatal Sertoli cells was associated with high plasma testosterone
      concentrations (2.7-5.5 ng ml(-1)), whereas strong Sertoli cell immunoexpression
      was associated with baseline (approximately 0.12 ng ml(-1)) testosterone
      concentrations in infant animals and with > 10 ng ml(-1) in late pubertal and
      adult animals. Immunoexpression of androgen receptor and oestrogen receptor beta
      was also evaluated in co-twin males aged 4 and 35 weeks, after treatment from
      birth to 4 weeks or from week 25 to week 35, respectively, with either vehicle or
      with GnRH antagonist at a dose known to suppress the neonatal testosterone surge
      completely. Only GnRH antagonist treatment during weeks 25-35 reduced androgen
      receptor immunoexpression, whereas immunoexpression of oestrogen receptor beta
      was unaffected by treatment during either period. On the basis of these findings
      it is suggested that: (i) neonatal marmoset Sertoli cells may be targets
      primarily for oestrogens rather than androgens; (ii) androgen receptor expression
      in the testes of neonatal and infant marmosets is not regulated in a
      straightforward way by testosterone; and (iii) high neonatal concentrations of
      plasma testosterone are not absolutely necessary for expression of androgen
      receptor in marmoset testes at this time.

PMID- 11597307
TI  - A proton NMR study of the effect of a new intravasal injectable male
      contraceptive RISUG on seminal plasma metabolites.
AB  - Nuclear magnetic resonance (NMR) spectroscopy was used to quantify citrate,
      glucose, lactate, glycerophosphorylcholine and choline in seminal plasma from
      subjects injected with a new male contraceptive RISUG, a copolymer of styrene
      maleic anhydride dissolved in dimethyl sulphoxide, and in seminal plasma from
      normal ejaculates. No significant difference in the concentration of citrate was
      observed between the groups, indicating that the prostate is not affected by the
      contraceptive. The concentrations of glucose, lactate, glycerophosphorylcholine
      and choline were significantly lower (P < 0.01) in subjects injected with RISUG
      compared with controls. In addition, metabolite ratios such as choline:citrate,
      citrate:lactate, choline:lactate and glycerophosphorylcholine:choline were
      calculated. Citrate:lactate and glycerophosphorylcholine:choline ratios were
      significantly lower in RISUG-injected subjects than in controls (P < 0.01),
      thereby indicating the occurrence of partial obstructive azoospermia. The most
      important finding of the present study was that the intervention of RISUG in the
      vas deferens even for a period as long as 8 years is absolutely safe and does not
      lead to prostatic diseases.

PMID- 11597308
TI  - Maternal nutrition and reproduction of daughters in wild house mice (Mus
      musculus).
AB  - Food deprivation after weaning often has greater effects on the reproductive
      success of females than of males. However, if animals are deprived prenatally
      (that is, through food deprivation of the mother during gestation), the
      reproductive success of males may be more adversely affected than that of females
      because of a disruption in the organizational effects of testosterone in neonatal
      male mice. The hypotheses that daughters of female mice deprived of food during
      gestation would have lower reproductive success than control daughters, but that
      the impact of maternal food deprivation would be lower for daughters than it
      would be for sons, was tested. There was no difference in the proportion of
      daughters of food-deprived and control mothers that produced one or two litters.
      However, the mean number of pups weaned in the second litters by daughters of
      control females (5.9 +/- 0.57 SEM) was greater than the number of pups weaned by
      daughters of food-deprived females (4.5 +/- 0.65 SEM). There were no differences
      in the mean birth or weaning body weights of offspring. Therefore, maternal food
      deprivation in mice may have a small but significant effect on the reproductive
      success of daughters. However, studies of sons born to females that were
      subjected to the same food deprivation protocol indicate that maternal food
      deprivation may have a much greater effect on the reproduction of sons than on
      that of daughters.

PMID- 11597309
TI  - Transmission electron microscopy studies of the zona reaction in pig oocytes
      fertilized in vivo and in vitro.
AB  - The aim of this study was to determine the ultrastructure of cross-sectioned
      zonae pellucidae of in vitro-matured and ovulated pig oocytes before or after
      sperm penetration in vitro and in vivo, respectively. The in vitro and in vivo
      (ovulated) oocytes and zygotes (fertilized in vitro and in vivo) were fixed with
      glutaraldehyde either directly or after pretreatment with ruthenium red and
      saponin, processed and then examined using transmission electron microscopy. The
      thickness of the zona pellucida, as measured on the section of the specimens with
      largest diameter fixed with glutaraldehyde, differed between the in vivo (9.19 +/
      0.47 microm) and in vitro (5.95 +/- 0.51 microm) oocytes. The in vivo oocytes
      had a rather thick external mesh-like structure, whereas it was much thinner in
      the in vitro oocytes. This mesh-like external rim was less apparent in both in
      vivo and in vitro zygotes. Obvious differences in the density of the lattice
      formed by the fixed zonae pellucidae were visible between the outer and inner (ad
      oolemmal) zonae. The outer area always formed a concentrically arrayed fibrillar
      network, whereas the inner area showed a much more compact, trabecule-like mesh.
      However, both areas, but particularly the outer network, were much more compacted
      after the zona reaction. Clear differences in the degree of fibrillar aggregation
      of the inner zona area were also observed between in vitro and in vivo zygotes,
      being much higher in the latter. This fibrillar network was more clearly visible
      in the zygotes pretreated with ruthenium red and saponin; the in vitro zygotes
      had a fibrillar, radially oriented set of parallel fibrils, whereas it was much
      more aggregated and trabecule-like in the in vivo zygotes. These results
      demonstrate that the fine structure of the zona pellucida and the zona reaction
      at sperm penetration differ between pig oocytes fertilized in vivo and in vitro.
      Moreover, the ultrastructure of the outer and inner pig zonae pellucidae has a
      different network organization.

PMID- 11597310
TI  - A Doppler ultrasonographic study of cyclic changes of ovarian perfusion in the
      Beagle bitch.
AB  - Changes in intraovarian arterial blood flow were monitored by means of colour
      coded and pulsed Doppler ultrasonography in Beagle bitches during the normal
      oestrous cycle (n = 11) and pregnancy (n = 3), and at PGF(2alpha)-induced
      luteolysis (n = 4). The ultrasonographic findings were related to the
      reproductive stage of the bitch, as determined by vaginoscopical and cytological
      criteria, and by the concentrations of oestradiol, LH and progesterone in
      peripheral blood plasma. Colour-coded Doppler ultrasonography was used to
      visualize and estimate intraovarian vascularization, and pulsed Doppler
      ultrasonography was used to measure the arterial blood flow. The systolic and
      diastolic peak velocities, the end-diastolic velocity, and the pulsatility index
      and resistance index were calculated for quantitative analysis of the Doppler
      waveforms. Intraovarian perfusion increased gradually during pro-oestrus. A
      marked enhancement of intraovarian colouring and blood flow velocities, and a
      decline in the indices for pulsatility and resistance were observed in the
      preovulatory period. Maximum perfusion was observed at ovulation and during the
      early luteal phase. Significant differences (P < 0.05) were detected for the
      values of all calculated Doppler parameters 2 days before and 2 days after
      ovulation. Intraovarian blood flow decreased gradually in accordance with luteal
      regression. Treatment with PGF(2alpha) caused a distinct decline in luteal
      activity and a concomitant reduction in intraovarian perfusion. The values of
      blood flow parameters found during the luteal phase of pregnant bitches were
      comparable to those of the normocyclic bitches. Doppler ultrasonography of the
      intraovarian arteries in bitches provides complementary information about cyclic
      changes of ovarian function.

PMID- 11597311
TI  - Generation of live rat offspring by intrauterine insemination with epididymal
      spermatozoa cryopreserved at -196 degrees C.
AB  - This study reports the development of a reliable method for cryopreservation of
      rat epididymal spermatozoa and the production of live young by artificial
      insemination using these cryopreserved spermatozoa. The motility and membrane
      integrity of rat spermatozoa were investigated after spermatozoa had been
      subjected to physical stress and frozen with various concentrations of glycerol
      (0, 3 and 6%) either in the presence or absence of Equex Stem as cryoprotective
      agents. The ability of cryopreserved spermatozoa to generate normal offspring by
      intrauterine insemination was also evaluated. Rat spermatozoa that had been
      centrifuged at 700 g for 5 min showed a significant decrease in motility compared
      with non-centrifuged spermatozoa. In addition, after centrifugation three times
      the percentage of membrane-intact spermatozoa decreased to approximately 0%. The
      percentage of membrane-intact spermatozoa was significantly higher (P < 0.01) in
      semen samples that had been frozen in medium without glycerol than in samples
      frozen in medium with 3% glycerol. Although the addition of 0.7% Equex Stem to
      medium without glycerol or with 3% glycerol did not influence rates of sperm
      motility after freezing and thawing, the percentage of membrane-intact
      spermatozoa was improved by the presence of 0.7% Equex (P < 0.05). Therefore, rat
      spermatozoa were handled gently to avoid physical stress and were frozen in
      medium containing 23% egg yolk, 8% lactose monohydrate and 0.7% Equex Stem, at pH
      7.4 adjusted with 10% Tris(hydroxymethyl)aminomethane solution. Thirteen female
      rats were inseminated into the oviductal end of both uterine horns with frozen
      thawed spermatozoa. Forty-one normal live offspring were obtained from nine of
      the inseminated females. These results indicate that frozen-thawed rat
      spermatozoa can generate normal offspring. To our knowledge, this procedure is
      the first successful production of offspring using spermatozoa cryopreserved in
      liquid nitrogen.

PMID- 11597312
TI  - Kinetic characterization of the changes in protein tyrosine phosphorylation of
      membranes, cytosolic Ca2+ concentration and viability in boar sperm populations
      selected by binding to oviductal epithelial cells.
AB  - On reaching the oviduct, spermatozoa are retained in the isthmic region of the
      oviduct until ovulation occurs. The essential steps of capacitation are co
      ordinated in this region. In this study, a primary cell culture system of
      oviductal epithelial cells was established to investigate sperm binding to
      oviductal epithelium and modulation of sperm function during incubation under
      capacitating conditions in co-culture with oviductal epithelial cells. Epithelial
      cells were stripped from the oviducts of sows and cultivated for 5-7 days on Lab
      Tek Chamber slides on Matrigel. The preparations on chamber slides and
      suspensions of control spermatozoa were incubated for 3 h in Tyrode's albumin
      lactate pyruvate (TALP) medium. At 3, 30, 60, 90 and 180 min the free-swimming
      spermatozoa were collected by washing, and membrane integrity, tyrosine
      phosphorylation patterns and [Ca(2+)](i) of bound, unbound and control
      spermatozoa were assessed with fluorescent probes (propidium iodide, Cy-3 and
      fluo-3-AM). The cells bound to oviductal epithelial cells showed reduced
      cytosolic Ca(2+) concentration, reduced and almost absent tyrosine
      phosphorylation of membrane proteins and higher viability at the time of the
      first sampling. Increases in Ca(2+) concentration and cell death occurred much
      more slowly during incubation in cells bound to oviductal epithelial cells
      compared with free-swimming spermatozoa, and no changes in tyrosine
      phosphorylation were observed. The preferential binding of viable, low-Ca(2+)
      cells with suppressed tyrosine phosphorylation and slower functional modulation
      of boar spermatozoa attached to oviductal epithelial cells might represent a
      mechanism for selecting functionally competent spermatozoa and prolonging their
      lifespan by delaying capacitation in the oviductal reservoir.

PMID- 11597313
TI  - Incidence of apoptosis in granulosa cells from immature human follicles.
AB  - The aim of this study was to investigate the incidence of apoptosis in granulosa
      cells from immature human follicles undergoing in vitro maturation (IVM) and to
      compare the incidence of apoptotic granulosa cells (i) between FSH-primed and
      unprimed normal ovaries and (ii) between polycystic and normal ovaries.
      Furthermore, the incidence of apoptosis was related to maturation and subsequent
      fertilization and cleavage of the oocytes from the corresponding ovary. Seventy
      women undergoing 70 IVM cycles were included. Group 1 consisted of patients with
      normal ovaries (n = 52) and group 2 consisted of patients with polycystic ovaries
      (n = 18). Patients in group 1 were subdivided into two groups according to
      priming with FSH before aspiration. In group 1a (n = 27 cycles) oocytes were
      obtained in unstimulated cycles. In group 1b (n = 25 cycles) oocytes were
      obtained after priming with recombinant FSH for 3 days initiated on day 3 after
      spontaneous menstruation. In group 2 all patients were primed with recombinant
      FSH for 3 days before aspiration. Aspiration was performed transvaginally and
      cumulus-enclosed oocytes were matured for 28-30 h before fertilization. Granulosa
      cells were collected from follicular aspirates. An APOPTAG detection kit was used
      to stain the granulosa cells and to detect apoptosis. The incidence of apoptosis
      in granulosa cells was decreased in follicles from FSH-primed normal ovaries
      compared with follicles from unprimed normal ovaries and FSH-primed polycystic
      ovaries. No difference was found between granulosa cells from FSH-primed
      polycystic ovaries and granulosa cells from unstimulated normal ovaries. No
      differences in maturation rate, fertilization rate, cleavage rate and
      implantation rate were observed when oocytes from a polycystic ovary were
      compared with oocytes from an unstimulated normal ovary. In unstimulated cycles,
      the ovaries were grouped according to the presence of a dominant follicle. The
      incidence of apoptosis was significantly higher in granulosa cells from an ovary
      without a dominant follicle compared with granulosa cells from an ovary with a
      dominant follicle. The rates of maturation, fertilization and cleavage did not
      differ between the two groups.

PMID- 11597314
TI  - Effect of ascorbic acid on health and morphology of bovine preantral follicles
      during long-term culture.
AB  - During ovarian folliculogenesis, ascorbic acid may be involved in collagen
      biosynthesis, steroidogenesis and apoptosis. The aims of this study were to
      determine the effects of ascorbic acid on bovine follicle development in vitro.
      Preantral follicles were cultured for 12 days in serum-free medium containing
      ascorbic acid (50 microg ml(-1)). Half of the medium was replaced every 2 days,
      and conditioned medium was analysed for oestradiol and matrix metalloproteinase 2
      (MMP-2) and MMP-9 secretion. On day 12, cell death was assessed by TdT-mediated
      dUTP-biotin nick end labelling (TUNEL). In the absence of serum, there was
      significant (P < 0.05) follicle growth and oestradiol secretion over the 12 day
      culture period. Ascorbic acid had no effect on these parameters. The addition of
      serum from day 0 stimulated follicle growth (P < 0.05), but compromised follicle
      integrity. By day 12 of culture, a higher proportion of follicles remained intact
      in the presence of ascorbic acid in serum-free conditions (P < 0.05), and
      significantly (P < 0.01) less granulosa and theca cell death was observed in
      these follicles than in control follicles. Moreover, ascorbic acid significantly
      (P < 0.05) increased production of MMP-9, an enzyme involved in basement membrane
      remodelling. In conclusion, this culture system was capable of supporting
      follicle differentiation over the 12 day culture period. Furthermore, ascorbic
      acid maintains bovine follicle health and basement membrane remodelling in vitro.

PMID- 11597315
TI  - Recent advances in technologies for the detection of occult metastatic cells in
      bone marrow of breast cancer patients.
AB  - Approximately half of breast cancer patients with stage I-III disease will suffer
      metastatic disease despite resection with tumour-free margins. In 30-40% of these
      patients, individual carcinoma cells can already be detected at the time of
      primary therapy in cytological bone marrow preparations using
      immunocytochemistry. Numerous prospective clinical studies have shown that the
      presence of occult metastatic cells in bone marrow is prognostically relevant to
      patient survival. Only a few studies failed to do so, thus stimulating a critical
      discussion on the methodology and clinical value of bone marrow analysis. The
      potential for obtaining improved prognostic information on patient outcome, for
      monitoring tumour cell eradication during adjuvant and palliative systemic
      therapy, and for specifically targeting tumour biological therapies are
      intriguing clinical opportunities that may be afforded by bone marrow analysis.
      Standardized and robust methodology is a prerequisite for clinical application of
      these techniques, however.

PMID- 11597316
TI  - The E-cadherin/catenin complex: an important gatekeeper in breast cancer
      tumorigenesis and malignant progression.
AB  - E-cadherin is a cell-cell adhesion protein fulfilling a prominent role in
      epithelial differentiation. Data from model systems suggest that E-cadherin is a
      potent invasion/tumor suppressor of breast cancer. Consistent with this role in
      breast cancer progression, partial or complete loss of E-cadherin expression has
      been found to correlate with poor prognosis in breast cancer patients. The E
      cadherin gene (CDH1) is located on human chromosome 16q22.1, a region frequently
      affected with loss of heterozygosity in sporadic breast cancer. Invasive lobular
      breast carcinomas, which are typically completely E-cadherin-negative, often show
      inactivating mutations in combination with loss of heterozygosity of the wild
      type CDH1 allele. Mutations were found at early noninvasive stages, thus
      associating E-cadherin mutations with loss of cell growth control and defining
      CDH1 as the tumor suppressor for the lobular breast cancer subtype. Ductal breast
      cancers in general show heterogeneous loss of E-cadherin expression, associated
      with epigenetic transcriptional downregulation. It is proposed that the
      microenvironment at the invasive front is transiently downregulating E-cadherin
      transcription. This can be associated with induction of nonepithelial cadherins.

PMID- 11597317
TI  - BRCA2 and homologous recombination.
AB  - Two recent papers provide new evidence relevant to the role of the breast cancer
      susceptibility gene BRCA2 in DNA repair. Moynahan et al provide genetic data
      indicating a requirement for BRCA2 in homology-dependent (recombinational) repair
      of DNA double-strand breaks. The second paper, by Davies et al, begins to address
      the mechanism through which BRCA2 makes its contribution to recombinational
      repair. BRCA2 appears to function in recombination via interactions with the
      major eukaryotic recombinase RAD51 [1,2,3]. We briefly review the context in
      which the two studies were carried out, we comment on the results presented, and
      we discuss models designed to account for the role of BRCA2 in RAD51-mediated
      repair.

PMID- 11597318
TI  - Mutations in normal breast tissue and breast tumours.
AB  - The accumulation of mutations is a feature of all normal cells. The probability
      of any individual gene in any cell acquiring a mutation is, however, low. Cancer
      is therefore a rare disease in comparison with the number of susceptible cells.
      Mutations in normal tissue are stochastic, vary widely among cells and are
      therefore difficult to detect using standard methods because each change is so
      rare. If, however, a tissue such as the breast undergoes considerable clonal
      expansion, particularly if relatively late in life, normal tissue may have
      accumulated many thousands of detectable mutations. Since breast cancers are
      clonal and have almost certainly undergone many more cell divisions than normal
      cells, each tumour may have many millions of mutations, most of which are
      entirely innocent and some of which have accumulated in the cell of origin prior
      to tumorigenesis. Despite some claims to the contrary, even at normal mutation
      rates, clonal expansion within a tumour is quite sufficient to account for the
      mutations of five or six genes that are generally supposed necessary for
      carcinogenesis to occur. Hypermutability does, however, contribute to the
      pathogenesis of many cancers and, although evidence is indirect in breast cancer,
      may take forms such as karyotypic instability via centrosome amplification.

PMID- 11597319
TI  - Phosphoinositide 3-kinase signalling in breast cancer: how big a role might it
      play?
AB  - Phosphoinositide 3-kinase (PI3K) was first identified as a lipid kinase activity
      associated with the products of viral oncogenes and with activated protein
      tyrosine kinases. Since those early studies, the PI3K superfamily has grown to
      embrace at least 12 structurally and functionally related enzymes present in the
      human genome, some of which have protein kinase activity but not lipid kinase
      activity. Evidence is emerging that PI3K superfamily members, and components of
      PI3K signalling, play a role in the development of many human cancers. In this
      review, the PI3K family of enzymes and their signalling is reviewed, with
      particular reference to possible involvement in breast cancer.

PMID- 11597320
TI  - Hypoxia and oxidative stress in breast cancer. Hypoxia signalling pathways.
AB  - Hypoxia-inducible factor-1 (HIF), which is centrally involved in physiological
      oxygen homeostasis, is also activated in the majority of tumours. Activation of
      HIF can occur through genetic mechanisms or as a result of hypoxia within the
      tumour microenvironment. In some cases HIF activation appears to be intimately
      linked to the proliferative stimulus itself. HIF affects patterns of gene
      expression and tumour growth, although precise effects vary between tumour types.
      Modulation of HIF activity, if correctly applied, may be therapeutically
      beneficial in tumour therapy.

PMID- 11597321
TI  - Hypoxia and oxidative stress in breast cancer. Hypoxia and tumourigenesis.
AB  - The microenvironmental hypoxia that arises as a consequence of the development of
      a solid tumour also acts to promote tumour growth. Hypoxia induces the expression
      of key components of the angiogenic and apoptotic signalling cascades, the
      glycolytic pathway and various cell-cycle control proteins. At the cellular level
      it mediates the infiltration and accumulation of tumour-associated macrophages
      within avascular tumour regions. Complex interactions between tumour cell and
      macrophage hypoxia-regulated gene products and their associated pathways form the
      basis for the hypoxic promotion of tumourigenesis and malignant progression.

PMID- 11597322
TI  - Hypoxia and oxidative stress in breast cancer. Oxidative stress: its effects on
      the growth, metastatic potential and response to therapy of breast cancer.
AB  - Reactive oxygen species (ROS) damage DNA, but the role of ROS in breast carcinoma
      may not be limited to the mutagenic activity that drives carcinoma initiation and
      progression. Carcinoma cells in vitro and in vivo are frequently under persistent
      oxidative stress. In the present review, we outline potential causes of oxygen
      radical generation within carcinoma cells and explore the possible impact of
      oxidative stress on the clinical outcome of breast carcinoma.

PMID- 11597323
TI  - Hypoxia and oxidative stress. Tumour hypoxia--therapeutic considerations.
AB  - Conclusive research has shown that regions of acute/chronic hypoxia, which exist
      within the majority of solid tumours, have a profound influence on the
      therapeutic outcome of cancer chemotherapy and radiotherapy and are a strong
      prognostic factor of disease progression and survival. A strong argument
      therefore exists for assessing the hypoxic fraction of tumours, prior to patient
      treatment, and to tailor this treatment accordingly. Tumour hypoxia also provides
      a powerful physiological stimulus that can be exploited as a tumour-specific
      condition, allowing for the rationale design of hypoxia-activated anticancer
      drugs or novel hypoxia-regulated gene therapy strategies.

PMID- 11597324
TI  - Characterization of adjacent breast tumors using oligonucleotide microarrays.
AB  - BACKGROUND: Current methodology often cannot distinguish second primary breast
      cancers from multifocal disease, a potentially important distinction for clinical
      management. In the present study we evaluated the use of oligonucleotide-based
      microarray analysis in determining the clonality of tumors by comparing gene
      expression profiles. METHOD: Total RNA was extracted from two tumors with no
      apparent physical connection that were located in the right breast of an 87-year
      old woman diagnosed with invasive ductal carcinoma (IDC). The RNA was hybridized
      to the Affymetrix Human Genome U95A Gene Chip (12,500 known human genes) and
      analyzed using the Gene Chip Analysis Suite 3.3 (Affymetrix, Inc, Santa Clara,
      CA, USA) and JMPIN 3.2.6 (SAS Institute, Inc, Cary, NC, USA). Gene expression
      profiles of tumors from five additional patients were compared in order to
      evaluate the heterogeneity in gene expression between tumors with similar
      clinical characteristics. RESULTS: The adjacent breast tumors had a pairwise
      correlation coefficient of 0.987, and were essentially indistinguishable by
      microarray analysis. Analysis of gene expression profiles from different
      individuals, however, generated a pairwise correlation coefficient of 0.710.
      CONCLUSION: Transcriptional profiling may be a useful diagnostic tool for
      determining tumor clonality and heterogeneity, and may ultimately impact on
      therapeutic decision making.

PMID- 11597325
TI  - Hormone replacement therapy use dramatically increases breast oestrogen receptor
      expression in obese postmenopausal women.
AB  - BACKGROUND: It is known that use of hormone replacement therapy (HRT) by
      postmenopausal women increases the risk of breast cancer. METHOD: In this study,
      oestrogen receptor (ER)-alpha expression is examined using standard
      immunoperoxidase technique. RESULTS: Normal breast samples of 11 Australian
      postmenopausal women have been included in the ER-alpha study; the result showed
      a strong correlation (r(2) = 0.80) between ER-alpha expression in normal breast
      epithelial cells and body mass index (BMI) in normal women who currently use HRT.
      CONCLUSION: This finding confirms that the possibility of increased risk of
      breast cancer associated with increased ER-alpha expression in normal breast
      epithelial cells, in turn associated with high BMI and the use of HRT.

PMID- 11597326
TI  - The intronic G13964C variant in p53 is not a high-risk mutation in familial
      breast cancer in Australia.
AB  - BACKGROUND: Mutations in BRCA1 and BRCA2 account for approximately 50% of breast
      cancer families with more than four affected cases, whereas exonic mutations in
      p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently
      reported that an intronic variant of p53--G13964C--occurred in three out of 42
      (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic'
      breast cancer control individuals (P = 0.0003). If this relatively frequent
      occurrence of G13964C in familial breast cancer and absence in control
      individuals were confirmed, then this would suggest that the G13964C variant
      plays a role in breast cancer susceptibility. METHOD: We genotyped 71 familial
      breast cancer patients and 143 control individuals for the G13964C variant using
      polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP)
      analysis. RESULTS: Three (4.2%; 95% confidence interval [CI] 0-8.9%) G13964C
      heterozygotes were identified. The variant was also identified in 5 out of 143
      (3.5%; 95% CI 0.6-6.4%) control individuals without breast cancer or a family
      history of breast cancer, however, which is no different to the proportion found
      in familial cases (P = 0.9). CONCLUSION: The present study would have had 80%
      power to detect an odds ratio of 4.4, and we therefore conclude that the G13946C
      polymorphism is not a 'high-risk' mutation for familial breast cancer.

PMID- 11597329
TI  - A wormer's eye view.
AB  - A report on the thirteenth international Caenorhabditis elegans meeting,
      University of California, Los Angeles, USA, 22-26 June 2001.

PMID- 11597330
TI  - The nucleosome: from wallflower to Queen of the Ball.

PMID- 11597331
TI  - Unraveling immunology.
AB  - A report on the 11th International Congress of Immunology, Stockholm, Sweden, 22
      27 July 2001.

PMID- 11597332
TI  - Ubiquitin junction, what's your function?
AB  - A report on the Ubiquitin and Intracellular Protein Degradation FASEB summer
      conference, Saxtons River, USA, 23-28 June 2001.

PMID- 11597333
TI  - Genomic-scale measurement of mRNA turnover and the mechanisms of action of the
      anti-cancer drug flavopiridol.
AB  - BACKGROUND: Flavopiridol, a flavonoid currently in cancer clinical trials,
      inhibits cyclin-dependent kinases (CDKs) by competitively blocking their ATP
      binding pocket. However, the mechanism of action of flavopiridol as an anti
      cancer agent has not been fully elucidated. RESULTS: Using DNA microarrays, we
      found that flavopiridol inhibited gene expression broadly, in contrast to two
      other CDK inhibitors, roscovitine and 9-nitropaullone. The gene expression
      profile of flavopiridol closely resembled the profiles of two transcription
      inhibitors, actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole
      (DRB), suggesting that flavopiridol inhibits transcription globally. We were
      therefore able to use flavopiridol to measure mRNA turnover rates comprehensively
      and we found that different functional classes of genes had distinct
      distributions of mRNA turnover rates. In particular, genes encoding apoptosis
      regulators frequently had very short half-lives, as did several genes encoding
      key cell-cycle regulators. Strikingly, genes that were transcriptionally
      inducible were disproportionately represented in the class of genes with rapid
      mRNA turnover. CONCLUSIONS: The present genomic-scale measurement of mRNA
      turnover uncovered a regulatory logic that links gene function with mRNA half
      life. The observation that transcriptionally inducible genes often have short
      mRNA half-lives demonstrates that cells have a coordinated strategy to rapidly
      modulate the mRNA levels of these genes. In addition, the present results suggest
      that flavopiridol may be more effective against types of cancer that are highly
      dependent on genes with unstable mRNAs.

PMID- 11597334
TI  - Analysis of strain and regional variation in gene expression in mouse brain.
AB  - BACKGROUND: We performed a statistical analysis of a previously published set of
      gene expression microarray data from six different brain regions in two mouse
      strains. In the previous analysis, 24 genes showing expression differences
      between the strains and about 240 genes with regional differences in expression
      were identified. Like many gene expression studies, that analysis relied
      primarily on ad hoc 'fold change' and 'absent/present' criteria to select genes.
      To determine whether statistically motivated methods would give a more sensitive
      and selective analysis of gene expression patterns in the brain, we decided to
      use analysis of variance (ANOVA) and feature selection methods designed to select
      genes showing strain- or region-dependent patterns of expression. RESULTS: Our
      analysis revealed many additional genes that might be involved in behavioral
      differences between the two mouse strains and functional differences between the
      six brain regions. Using conservative statistical criteria, we identified at
      least 63 genes showing strain variation and approximately 600 genes showing
      regional variation. Unlike ad hoc methods, ours have the additional benefit of
      ranking the genes by statistical score, permitting further analysis to focus on
      the most significant. Comparison of our results to the previous studies and to
      published reports on individual genes show that we achieved high sensitivity
      while preserving selectivity. CONCLUSIONS: Our results indicate that molecular
      differences between the strains and regions studied are larger than indicated
      previously. We conclude that for large complex datasets, ANOVA and feature
      selection, alone or in combination, are more powerful than methods based on fold
      change thresholds and other ad hoc selection criteria.

PMID- 11597335
TI  - Characterization of alternatively spliced products and tissue-specific isoforms
      of USP28 and USP25.
AB  - BACKGROUND: The ubiquitin-dependent protein degradation pathway is essential for
      the proteolysis of intracellular proteins and peptides. Deubiquitinating enzymes
      constitute a complex protein family involved in a multitude of cellular
      processes. The ubiquitin-specific proteases (UBP) are a group of enzymes whose
      predicted function is to reverse the ubiquitinating reaction by removing
      ubiquitin from a large variety of substrates. We have lately reported the
      characterization of human USP25, a specific-ubiquitin protease gene at 21q11.2,
      with a specific pattern of expression in murine fetal brains and adult testis.
      RESULTS: Database homology searches at the DNA and protein levels and cDNA
      library screenings led to the identification of a new UBP member in the human
      genome, named USP28, at 11q23. This novel gene showed preferential expression in
      heart and muscle. Moreover, cDNA, expressed sequence tag and RT-PCR analyses
      provided evidence for alternatively spliced products and tissue-specific
      isoforms. Concerning function, USP25 overexpression in Down syndrome fetal brains
      was shown by real-time PCR. CONCLUSIONS: On the basis of the genomic and protein
      sequence as well as the functional data, USP28 and USP25 establish a new
      subfamily of deubiquitinating enzymes. Both genes have alternatively spliced
      exons that could generate protein isoforms with distinct tissue-specific
      activity. The overexpression of USP25 in Down syndrome fetal brains supports the
      gene-dosage effects suggested for other UBP members related to aneuploidy
      syndromes.

PMID- 11597337
TI  - The olfactory receptor family album.
AB  - Analysis of the human genome draft sequences has revealed a more complete
      portrait of the olfactory receptor gene repertoire in humans than was available
      previously. The new information provides a basis for deeper analysis of the
      functions of the receptors, and promises new insights into the evolutionary
      history of the family.

PMID- 11597336
TI  - The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G+C Gram
      positive bacteria.
AB  - BACKGROUND: The genome of Mycobacterium tuberculosis H37Rv has five copies of a
      cluster of genes known as the ESAT-6 loci. These clusters contain members of the
      CFP-10 (lhp) and ESAT-6 (esat-6) gene families (encoding secreted T-cell antigens
      that lack detectable secretion signals) as well as genes encoding secreted, cell
      wall-associated subtilisin-like serine proteases, putative ABC transporters, ATP
      binding proteins and other membrane-associated proteins. These membrane
      associated and energy-providing proteins may function to secrete members of the
      ESAT-6 and CFP-10 protein families, and the proteases may be involved in
      processing the secreted peptide. RESULTS: Finished and unfinished genome
      sequencing data of 98 publicly available microbial genomes has been analyzed for
      the presence of orthologs of the ESAT-6 loci. The multiple duplicates of the ESAT
      6 gene cluster found in the genome of M. tuberculosis H37Rv are also conserved in
      the genomes of other mycobacteria, for example M. tuberculosis CDC1551, M.
      tuberculosis 210, M. bovis, M. leprae, M. avium, and the avirulent strain M.
      smegmatis. Phylogenetic analyses of the resulting sequences have established the
      duplication order of the gene clusters and demonstrated that the gene cluster
      known as region 4 (Rv3444c-3450c) is ancestral. Region 4 is also the only region
      for which an ortholog could be found in the genomes of Corynebacterium
      diphtheriae and Streptomyces coelicolor. CONCLUSIONS: Comparative genomic
      analysis revealed that the presence of the ESAT-6 gene cluster is a feature of
      some high-G+C Gram-positive bacteria. Multiple duplications of this cluster have
      occurred and are maintained only within the genomes of members of the genus
      Mycobacterium.

PMID- 11597338
TI  - Functional genomics and metal metabolism.
AB  - Metal ions are essential nutrients, yet they can also be toxic if they over
      accumulate. Homeostatic mechanisms and detoxification systems therefore precisely
      control their intracellular levels and distribution. The tools of functional
      genomics are rapidly accelerating understanding in this field, particularly in
      the yeast Saccharomyces cerevisiae.

PMID- 11597339
TI  - An amphibian with ambition: a new role for Xenopus in the 21st century.
AB  - Much of our knowledge about the mechanisms of vertebrate early development comes
      from studies using Xenopus laevis. The recent development of a remarkably
      efficient method for generating transgenic embryos is now allowing study of late
      development and organogenesis in Xenopus embryos. Possibilities are also emerging
      for genomic studies using the closely related diploid frog Xenopus tropicalis.

PMID- 11597341
TI  - Access to care for seniors -- dental concerns.

PMID- 11597340
TI  - Having a BLAST with bioinformatics (and avoiding BLASTphemy).
AB  - Searching for similarities between biological sequences is the principal means by
      which bioinformatics contributes to our understanding of biology. Of the various
      informatics tools developed to accomplish this task, the most widely used is
      BLAST, the basic local alignment search tool. This article discusses the
      principles, workings, applications and potential pitfalls of BLAST, focusing on
      the implementation developed at the National Center for Biotechnology
      Information.

PMID- 11597342
TI  - Esthetic option for the implant-supported single-tooth restoration -- treatment
      sequence with a ceramic abutment.
AB  - A single implant-supported restoration is one treatment alternative to consider
      for the replacement of a missing tooth. Technological advances in materials and
      machining have led to the development of a densely sintered aluminum oxide
      ceramic abutment, designed and machined using CAD/CAM technology. This
      manufacturing method improves management of the subgingival depth of the
      crown/abutment interface and enhances the esthetic qualities of the restoration.
      However, since this ceramic abutment has less mechanical resistance than metal
      abutments, its use should be confined to the restoration of incisors and
      premolars not subjected to excessive occlusal forces.

PMID- 11597343
TI  - Orthodontically assisted restorative dentistry.
AB  - As treatment expectations of dental patients continue to escalate we, as
      restorative dentists, must provide an interdisciplinary treatment approach to
      ensure optimum results for our patients. In recent years the disciplines of
      periodontics, endodontics and oral surgery have continued to develop closer
      working relationships with the field of restorative dentistry. Unfortunately,
      this is not the common relationship that exists with the discipline of
      orthodontics. Most orthodontic therapy is directed at the treatment of
      malocclusion and is conducted with limited or no input from the restorative
      dentist. Orthodontics offers countless ways of assisting the restorative dentist
      in achieving treatment goals. Several of these orthodontic opportunities to
      enhance the restorative treatment plan are reviewed.

PMID- 11597344
TI  - Occlusal stability in implant prosthodontics -- clinical factors to consider
      before implant placement.
AB  - The success of any prosthetic design depends on proper management of the
      occlusion. The clinical variables influencing occlusal stability must be
      determined and considered in the design of the final prosthesis. This paper
      outlines some of these variables.

PMID- 11597345
TI  - A multi-centre study of Osseotite implants supporting mandibular restorations: a
      3-year report.
AB  - This multi-centre study evaluated the performance of the Osseotite implant in the
      mandibular arch. Osseotite implants (n = 688) were placed in 172 patients; 43.5%
      were placed in the anterior mandible and 66.5% in the posterior mandible. Fifteen
      per cent of the implants were placed in soft bone, 56.9% in normal bone and 28.1%
      in dense bone. During placement, 49.9% of the implants were identified as having
      a tight fit, 48.6% a firm fit and 1.5% a loose fit. About one-third of the
      implants (32.4%) were short (10 mm in length or less). After 36 months, only 5
      implants had been lost, for a cumulative survival rate of 99.3%. The 3-year
      results of this study indicate a high degree of predictability with placement of
      Osseotite implants in the mandibular arch.

PMID- 11597346
TI  - Molar restorations supported by 2 implants: an alternative to wide implants.
AB  - The single-tooth restoration has become one of the most widely used procedures in
      implant dentistry. Improvements to the abutment implant interface design, wider
      implant platforms and the increased use of cemented restorations have greatly
      enhanced this procedure. Nonetheless, limitations in the volume of underlying
      bone and heavy occlusal loads, with or without parafunctional habits, still
      contribute to occasional disappointments in restoration stability. The use of 2
      implants to restore a molar has been shown to eliminate problems associated with
      bone volume and prosthetic stability. One of the most significant barriers to the
      widespread use of this concept has been the limitation of the size of implants
      and their associated prosthetic components. This paper presents the use of 2
      implants to replace a single molar using implants and prosthetic components in
      the Astra Tech Dental Implant System.

PMID- 11597347
TI  - Effect of phospholipid on trichosanthin adsorption at the air-water interface.
AB  - Trichosanthin (TCS) is a toxic protein with multiple pharmacological properties.
      It belongs to the type I ribosome inactivating protein (RIP) family and can
      inactivate the eukaryotic ribosome through its RNA N-glycosidase activity. The
      interaction between TCS and phospholipid membrane was thought to be essential for
      its physiological effect, for it must get across the cell membrane before it can
      enter the cytoplasm and exert its RIP function. In order to study the TCS
      phospholipid interaction, the difference between spontaneous and phospholipid
      induced adsorption of TCS at the air-water interface was investigated, and the
      results were analyzed according to the diffusion-penetration-rearrangement
      adsorption model. The results showed that both negatively charged 1,2-dipalmitoyl
      sn-glycero-3-phosphoglycerol (DPPG) and neutral 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine can accelerate the adsorption rate, while there exists a possible
      membrane induced conformational change of TCS which is specific for the
      negatively charged DPPG. We also proposed a revised model for the diffusion
      controlled initial adsorption period.

PMID- 11597348
TI  - Isolation and characterisation of the major outer membrane protein of Erwinia
      carotovora.
AB  - The purified major outer membrane protein (37275 Da) from the psychrotrophic
      phytopathogen Erwinia carotovora MFCL0 was structurally characterised by MALDI
      TOF mass spectrometry, N-terminal microsequencing and DNA sequence
      determinations, and secondary structure prediction analyses. The deduced amino
      acid sequence showed 76% and 72% of similarities with the Serratia marcescens and
      Escherichia coli OmpA proteins respectively. Dendrogram analysis allowed to point
      out that E. carotovora is close to the genus Serratia. After reconstitution into
      planar lipid bilayers, this major protein induced ion channels with a major
      conductance level of 630 pS in 1 M NaCl and a weak cationic selectivity. These
      functional and structural features allowed to identify this major outer membrane
      component of E. carotovora as an OmpA-like protein, i.e., a channel-forming
      protein which could be involved in the infection process of this phytopathogen
      agent.

PMID- 11597349
TI  - On the mechanisms of internalization and intracellular delivery mediated by pH
      sensitive liposomes.
AB  - We investigated the molecular mechanisms by which pH-sensitive liposomes surpass
      the cytoplasmic and endosomal membranes to deliver their aqueous contents into
      the cytoplasm. Various liposome formulations were evaluated for their efficacy to
      mediate intracellular delivery of encapsulated material, including a novel
      sterically stabilized pH-sensitive formulation ((DOPE:CHEMS:DSPE-PEG(2000)
      (6:4:0.3)) that was previously developed in our laboratories. In an attempt to
      fully characterize the nature of liposome-cell interactions different approaches
      based on a dual-labeling fluorescence assay were used. Our results indicate that
      the efficacy of interaction of pH-sensitive liposomes, both plain and sterically
      stabilized, with cells is strongly determined by the inclusion of DOPE in their
      composition, independently of the type of the amphiphilic stabilizer used. In
      fact, DOPE-containing liposomes shown to be non-pH sensitive by biophysical
      assays, mediated cytoplasmic delivery of their contents as efficiently as well
      known pH-sensitive formulations (e.g. DOPE:CHEMS). However, among the different
      formulations studied, DOPE:CHEMS liposomes were those exhibiting the highest
      extent of cell association. Moreover, our results with cells pretreated with
      metabolic inhibitors or lysosomotropic agents clearly indicate that DOPE
      containing liposomes are internalized essentially by endocytosis and that
      acidification of the endosomes is not the only mechanism involved in the
      destabilization of the liposomes inside the cell.

PMID- 11597350
TI  - Clostridium perfringens type A enterotoxin forms mepacrine-sensitive pores in
      pure phospholipid bilayers in the absence of putative receptor proteins.
AB  - Clostridium perfringens enterotoxin (CPE) is an important cause of food poisoning
      with no significant homology to other enterotoxins and its mechanism of action
      remains uncertain. Although CPE has recently been shown to complex with tight
      junction proteins, we have previously demonstrated that CPE increases ionic
      permeability in single Caco-2 cells using the whole-cell patch-clamp technique,
      thereby excluding any paracellular permeability. In this paper we demonstrate
      that CPE forms pores in synthetic phospholipid membranes in the absence of
      receptor proteins. The properties of the pores are consistent with CPE-induced
      permeability changes in Caco-2 cells suggesting that CPE has innate pore-forming
      ability.

PMID- 11597351
TI  - Encapsulation of DNA in negatively charged liposomes and inhibition of bacterial
      gene expression with fluid liposome-encapsulated antisense oligonucleotides.
AB  - Antisense therapy for the treatment of bacterial infections is a very attractive
      alternative to overcome drug resistance problems. However, the penetration of
      antisense oligonucleotides into bacterial cells is a major huddle that has
      delayed research and application in this field. In the first part of this study,
      we defined efficient conditions to encapsulate plasmid DNA and antisense
      oligonucleotides in a fluid negatively charged liposome. Subsequently, we
      evaluated the potential of liposome-encapsulated antisense oligonucleotides to
      penetrate the bacterial outer membrane and to inhibit gene expression in
      bacteria. It was found that 48.9+/-12% and 43.5+/-4% of the purified plasmid DNA
      and antisense oligonucleotides were respectively encapsulated in the liposomes.
      Using fluorescence-activated cell sorting analysis, it was shown, after
      subtraction of the fluorescence values due to the aggregation phenomenon measured
      at 4 degrees C, that about 57% of bacterial cells had integrated the encapsulated
      antisense oligonucleotides whereas values for free antisenses were negligible.
      The uptake of the encapsulated anti-lacZ antisense oligonucleotides resulted in a
      42% reduction of beta-galactosidase compared to 9% and 6% for the encapsulated
      mismatch antisense oligonucleotides and the free antisense oligonucleotides
      respectively. This work shows that it is possible to encapsulate relatively large
      quantities of negatively charged molecules in negative fluid liposomes and
      suggests that fluid liposomes could be used to deliver nucleic acids in bacteria
      to inhibit essential bacterial genes.

PMID- 11597352
TI  - Spin label electron paramagnetic resonance study in thylakoid membranes from a
      new herbicide-resistant D1 mutant from soybean cell cultures deficient in fatty
      acid desaturation.
AB  - The effect of fatty acid desaturation on lipid fluidity in thylakoid membranes
      isolated from the STR7 mutant was investigated by electron paramagnetic resonance
      (EPR) using spin label probes. The spectra of both 5- and 16-n-doxylstearic acid
      probes were measured as a function of the temperature between 10 and 305 K and
      compared to those of the wild type. This complete thermal evolution provides a
      wider picture of the dynamics. The spectra of the 5-n-doxylstearic acid probe as
      well as their temperature evolution were identical in both STR7 mutant and wild
      type thylakoids. However, differences were found with the 16-n-doxylstearic acid
      probe at temperatures between 230 and 305 K. The differences in the thermal
      evolution of the EPR spectra can be interpreted as a 5-10 K shift toward higher
      temperatures of the probe motional rates in the STR7 mutant as compared with that
      in the wild type. At temperatures below 230 K no differences were observed. The
      results indicated that the lipid motion in the outermost region of the thylakoids
      is the same in the STR7 mutant as in the wild type while the fluidity in the
      inner region of the STR7 mutant membrane decreases. Our data point out a picture
      of the STR7 thylakoid membrane in which the lipid motion is slower most probably
      as a consequence of fatty acid desaturation deficiency.

PMID- 11597353
TI  - Role of CFTR's PDZ1-binding domain, NBF1 and Cl(-) conductance in inhibition of
      epithelial Na(+) channels in Xenopus oocytes.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) inhibits
      epithelial Na(+) channels (ENaC). Evidence has accumulated that both Cl(-)
      transport through CFTR Cl(-) channels and the first nucleotide binding domain
      (NBF1) of CFTR are crucial for inhibition of ENaC. A PDZ binding domain (PDZ-BD)
      at the C-terminal end links CFTR to scaffolding and cytoskeletal proteins, which
      have been suggested to play an important role in activation of CFTR and
      eventually inhibition of ENaC. We eliminated the PDZ-BD of CFTR and coexpressed
      Na(+)/H(+)-exchange regulator factors together with CFTR and ENaC. The results do
      not support a role of PDZ-BD in inhibition of ENaC by CFTR. However, inhibition
      of ENaC was closely linked to Cl(-) currents generated by CFTR and was observed
      in the presence of Cl(-), I(-) or Br(-) but not gluconate. Therefore, functional
      NBF1 and Cl(-) transport are required for inhibition of ENaC in Xenopus oocytes,
      while the PDZ-BD is not essential.

PMID- 11597354
TI  - Effect of pH on the self-association of erythrocyte band 3 in situ.
AB  - The human erythrocyte anion exchanger (band 3) contains a cytoplasmic domain
      (cdb3) that exists in a reversible, pH-dependent structural equilibrium among
      three native conformations. To understand how this conformational equilibrium
      might influence the association state of band 3, we have incubated stripped
      erythrocyte membranes in solutions ranging from pH 6.0 to pH 10.5 and have
      examined the oligomeric state of the protein by size exclusion high performance
      liquid chromatography. We demonstrate that incubation of membranes in slightly
      acidic conditions favors dimer formation, whereas extended incubation at higher
      pHs (pH>9) leads to irreversible formation of an oligomeric species larger than
      the tetramer. Since the pH dependence of the conformational state of the
      cytoplasmic domain exhibits a similar pH profile, we suggest that the
      conformation of the cytoplasmic domain can modulate the self-association of band
      3. Importantly, this modulation would appear to require the structural
      interactions present within the intact protein, since the isolated membrane
      spanning domain does not display any pH dependence of association. The
      irreversible nature of the alkali-induced aggregation further suggests that a
      secondary reaction subsequent to band 3 association is required to stabilize the
      high molecular weight aggregate. Although we were able to eliminate covalent bond
      formation in this irreversible aggregation process, the exact nature of the
      secondary reaction remains to be elucidated.

PMID- 11597355
TI  - Development of three-dimensional power Doppler ultrasound imaging of
      fetoplacental vasculature.
AB  - To develop an off-line system for three-dimensional (3-D) ultrasound (US)
      reconstruction of fetoplacental vasculature using colour segmentation and
      reconstruction software and to determine sources of error in fully freehand
      ultrasound image acquisition. US images were acquired freehand with the Acuson
      Sequoia (5C 2-MHz transducer) using power Doppler. After digital transfer to a
      personal computer, CQ Analysis software (Kinetic Imaging Ltd, Liverpool, UK) was
      used to segment the colour information from these images, and the resulting 8-bit
      grey-scale images were used for 3-D rendering using commercial software
      (VoxBlast, Vaytek Inc., Fairfield, IA, USA). 2-D scanning, software and freehand
      acquisition accuracy were assessed using a linear test rig and distance and
      volume phantoms (Dansk Phantom Service Ltd); 2-D scanning accuracy was within
      1.3%, and software reconstruction accuracy within 1% for x and y planes and up to
      3% for the z plane. Fully freehand acquisition was associated with a 12% to 18%
      mean percentage error in distance measurement in the plane of acquisition.
      Volumetric reconstruction inaccuracy was between 1.5% and 19.7% for precisely
      separated images and between 16.2% and 39.2% for fully freehand image
      acquisition. Rendered 3-D US vascular images clearly delineated vascular anatomy
      within the placenta and cord. Fully freehand 3-D US does have a role in off-line
      reconstruction of vascular anatomy, although variability in the z plane precludes
      its use for volumetric measurement. (E-mail: a.welsh@ic.ac.uk)

PMID- 11597356
TI  - Vascularity index distribution within the testis: a technique for guiding
      testicular sperm extraction.
AB  - Azoospermia is defined as the absence of spermatozoa in the ejaculate, although
      some foci of spermatogenesis may exist in the testes of these men. Currently,
      there are no clinical, seminal or hormonal parameters for identifying
      spermatogenesis within the testis sufficient for achieving genetic offspring. As
      a result, multiple biopsies are performed at several arbitrary sites of both
      testes in search of spermatozoa. We developed a power Doppler (PD) ultrasound
      (US) image-based technique that predicts sites with the greatest potential for
      spermatogenesis. PDUS images of the testes of azoospermic men were acquired at
      seven cross-sections to reconstruct a 3-D matrix for constructing a spatial map
      of preferential regions where spermatozoa are most likely to exist. This
      technique may obviate the need for arbitrary multiple biopsies that inflict some
      degree of damage upon testicular tissue, and may increase the success rate of
      identifying viable spermatozoa in testicular biopsies.

PMID- 11597357
TI  - Real-time three-dimensional intracardiac echocardiography.
AB  - Using catheter-mounted 2-D array transducers, we have obtained real-time 3-D
      intracardiac ultrasound (US) images. We have constructed several transducers with
      64 channels inside a 12 French catheter lumen operating at 5 MHz. The transducer
      configuration may be side-scanning or beveled, with respect to the long axis of
      the catheter lumen. We have also included six electrodes to acquire simultaneous
      electrocardiograms. Using an open-chest sheep model, we inserted the catheter
      into the cardiac chambers to study the utility of in vivo intracardiac 3-D
      scanning. Images obtained include a cardiac four-chamber view, mitral valve,
      pulmonic valve, tricuspid valve, interatrial septum, interventricular septum and
      ventricular volumes. We have also imaged two electrophysiological interventional
      devices in the right atrium, performed an in vitro ablation study, and viewed the
      pulmonary veins in vitro.

PMID- 11597358
TI  - Improved 3-D-echocardiographic endocardial border delineation using the contrast
      agent FS069 (Optison) transesophageal studies in a porcine model.
AB  - 3-D echocardiography has the potential for quantitative assessment of regional
      wall motion. However, the 3-D procedures used to date do not provide the same
      spatial and temporal resolution as 2-D echocardiography, which results in
      problems with border delineation of the endocardium. There are, as yet, few
      studies testing if the use of contrast agent can improve endocardial definition
      in the 3-D data set. FS069 (Optison) was used for the first time for this purpose
      in the present study. A total of 12 mechanically-ventilated pigs were examined by
      transesophageal 3-D echocardiography, 1. using fundamental imaging and 2.
      following left-atrial injection of FS069 (Optison). The left ventricle was
      analyzed using an 18-segment model. Score with the value 0 (not visible), 1
      (moderately visible) and 2 (well defined) were used to rate endocardial
      definition. All segments were assessed both end-diastolic and end-systolic.
      Various LV regions were examined by grouping segments (anterior/lateral/inferior
      and basal/mid-ventricular/apical). Using the contrast agent, the proportion of
      nonvisible segments fell diastolic from 40 (18.5%) to 15 (6.9%), and systolic
      from 26 (12.0%) to 11 (5.1%). The proportion of well defined segments increased
      diastolic from 62 (28.7%) to 108 (50%) and systolic from 73 (33.8%) to 123
      (56.9%). The mean visibility score increased diastolic from 1.10 +/- 0.68 to 1.43
      +/- 0.62 (p < 0.001), systolic from 1.22 +/- 0.64 to 1.52 +/- 0.59 (p < 0.001).
      The benefit was greatest in regions where the visibility score was lowest without
      contrast: in the area of the lateral wall and systolic near the apex. In
      conclusion, the use of FS069 (Optison) results in significantly better
      endocardial delineation in the 3-D data set. This could be important in future
      for the 3-D echocardiographic assessment of regional wall motion.

PMID- 11597359
TI  - Alterations of myocardial ultrasonic tissue characterization by coronary
      angioplasty in patients with chronic stable coronary artery disease.
AB  - We conducted a study to delineate the alterations in the cyclic changes of
      myocardial ultrasonic integrated backscatter (IBS) in patients receiving
      angioplasty for chronic coronary artery disease. Ultrasonic tissue
      characterization (UTC) and dobutamine stress echocardiography were performed in
      43 patients before and 24 h after angioplasty, as well as before the follow-up
      angiography 3 months later. For segments being normokinetic with ischemic burden,
      the blunted amplitude and increased nadir deviation of IBS cyclic modulation
      recovered soon after angioplasty. For dyssynergic segments with contractile
      reserve, the angioplasty rebuilt the amplitude before the wall motion recovered,
      but corrected the nadir deviation tardily. In both circumstances, the coronary
      restenosis abolished the initial restoration. Those nonviable segments
      persistently revealed large deviations and small weighted amplitudes irrelevant
      to coronary lesions. The progress of myocardial ischemia, the development of wall
      motion dyssynergy and, then, the loss of viability, show different patterns of
      alterations in UTC after alleviating coronary obstructions.

PMID- 11597360
TI  - Ultrasonographic assessment of coronary flow reserve and abdominal fat in
      obesity.
AB  - Recent technological advances in transthoracic Doppler echocardiography (TTDE)
      have provided noninvasive measurement of coronary flow velocity reserve (CFVR).
      We aimed to quantitate a correlation between endothelial dysfunction and fat
      distribution. In 36 patients with obesity, 16 with noninsulin-dependent diabetes
      mellitus (DM) and 12 healthy volunteers, coronary flow velocity was measured at
      the distal site of the left anterior descending branch. CFVR was defined as the
      ratio of hyperemic (IV infusion of 0.15 mg/kg/min adenosine) to basal peak
      diastolic flow velocity. Abdominal wall fat index (AWFI) was estimated by
      ultrasonography. Insulin resistance was quantified by the euglycemic
      hyperinsulinemic clump method. AWFI was significantly related to CFVR (r = -0.46,
      p = 0.011) and insulin resistance (r = -0.71, p < 0.0001). CFVR could be
      noninvasively evaluated using TTDE. Coronary endothelial dysfunction indicated as
      CFVR, body fat distribution and insulin resistance was quantitatively correlated
      in obesity.

PMID- 11597361
TI  - Associations of aortic Windkessel function with age, gender and cardiovascular
      risk factors.
AB  - Aortic Windkessel function is thought to represent a potential cardiovascular
      risk factor. As an indicator for the function, we have recently introduced the
      decay index (DI). DI is the coefficient of an exponential function applied to the
      postpeak portion of internal carotid artery Doppler waveform, and is inversely
      associated with the function. This study compares DI with age, gender and
      traditional cardiovascular risk factors in 220 apparently healthy volunteers (59
      +/- 16 years). DI increased linearly with age (r = 0.51, p < 0.001), and was
      higher in women than in men at all ages (p < 0.001). Also, DI was positively
      associated with systolic blood pressure (beta = 0.17, p < 0.01) and diabetic
      medication (beta = 0.14, p < 0.05), independent of age (beta = 0.49, p < 0.0001),
      gender (beta = 0.27, p < 0.0001) and other traditional cardiovascular risk
      factors (model r(2) = 0.36). Based on the present results, the Windkessel
      function as assessed by DI declines with age and is lower in women. However, the
      associations with cardiovascular risk factors need to be established on a larger
      sample at higher cardiovascular risk.

PMID- 11597362
TI  - The use of cross-correlation analysis between high-frequency ultrasound images to
      measure longitudinal median nerve movement.
AB  - Impaired nerve movement can lead to nerve injury (e.g., carpal tunnel syndrome).
      A noninvasive method to measure nerve movement in longitudinal section would
      enable an extensive analysis of nerve entrapment syndromes. A method has been
      developed using cross-correlation between successive high-frequency ultrasound
      (US) images to measure longitudinal movement of nerve and muscle. Control
      "phantom" experiments demonstrated the accuracy and reliability of this method at
      velocities of 1-10 mm/s. Increasing the frame interval between the compared
      frames enabled the accurate calculation of slower velocities. The correlation
      algorithm successfully measured relative movement when the US transducer was
      moved 1-3 mm over the surface of the forearm. Median nerve movement was
      repeatedly measured in the forearm during 30 degrees passive wrist extension in
      three subjects (range 2.63-4.12 mm) and index finger extension in seven subjects
      (range 1.59-4.48 mm). Median nerve movement values were consistent with those
      from cadaver studies.

PMID- 11597363
TI  - A fast calibration method for 3-D tracking of ultrasound images using a spatial
      localizer.
AB  - We have developed a fast calibration method for computing the position and
      orientation of 2-D ultrasound (US) images in 3-D space where a position sensor is
      mounted on the US probe. This calibration is required in the fields of 3-D
      ultrasound and registration of ultrasound with other imaging modalities. Most of
      the existing calibration methods require a complex and tedious experimental
      procedure. Our method is simple and it is based on a custom-built phantom. Thirty
      N-fiducials (markers in the shape of the letter "N") embedded in the phantom
      provide the basis for our calibration procedure. We calibrated a 3.5-MHz sector
      phased-array probe with a magnetic position sensor, and we studied the accuracy
      and precision of our method. A typical calibration procedure requires
      approximately 2 min. We conclude that we can achieve accurate and precise
      calibration using a single US image, provided that a large number (approximately
      ten) of N-fiducials are captured within the US image, enabling a representative
      sampling of the imaging plane.

PMID- 11597364
TI  - Performance of ultrasound echo decomposition using singular spectrum analysis.
AB  - Diagnostic ultrasonography has its well-established role in medicine.
      Nevertheless, the quantitative characterisation of biological tissues by
      ultrasound (US) is still a main topic of research. Several parameters have been
      explored with this purpose, (e.g. attenuation, backscatter coefficient, US
      speed). More recently, mean scatterer space (MSS) has been proposed as a
      characterisation parameter. The objective of this work was to investigate the
      potential of the singular spectrum analysis (SSA) to estimate MSS. This method
      proposes the reconstruction of the periodic part of the original US signal from
      where the MSS of the medium can be estimated. SSA is applied to simulated and
      real backscattered echoes from a phantom and a bovine liver sample. Consistent
      results were obtained from both Monte-Carlo simulation and real data. They were
      compared with literature. Presently, precision, accuracy and sensibility of SSA
      are being investigated.

PMID- 11597365
TI  - Telemedicine in ultrasound: new solutions.
AB  - The transport of dynamic ultrasound (US) pictures as video files or streams no
      longer presents a problem. Despite teleconferencing, this method of transfer
      provides no active influence on the data sent for the receiving expert. We are
      evaluating a software-based 3-D US system that provides the new opportunity of an
      active US re-evaluation of a virtual patient. The 3-D volumes can be reanalyzed,
      time- and examiner-independent, wherever the device is installed. To test the
      clinical feasibility of this virtual US investigation, we installed the device in
      a peripheral hospital and in our US unit. The transfer of the volume (about 10 to
      15 MB) could be done with two parallel Integrated Services Digital Network (ISDN)
      lines with a conduction capacity of 128 KB/s. In this basic assessment, the
      transmission of US volumes of patients proved to be easy in the acquisition,
      quick in off-line transmission and reliable in off-line re-evaluation of the
      data.

PMID- 11597366
TI  - Doppler power variation from porcine blood under steady and pulsatile flow.
AB  - Although a number of recent studies have demonstrated that the echogenicity of
      blood varies as a function of time under pulsatile flow, the fundamental
      mechanisms responsible for it are still uncertain. To better understand this
      phenomenon, the Doppler power from porcine blood and polystyrene microsphere
      suspensions was measured at the center of the tube as functions of two crucial
      parameters, flow velocity and stroke rate (for pulsatile flow), under steady and
      pulsatile flow in a mock flow loop. In the present study, the experimental
      results were obtained with a 10-MHz pulsed Doppler system with a frequency
      response estimated more accurately by electronic injection, and validated by
      comparing to the radiofrequency (RF) signal acquired from the same Doppler
      instrument. The results show that the Doppler power from microspheres and porcine
      red blood cell (RBC) suspensions did not vary appreciably (< 2 dB), with either
      the speed or stroke rate (for pulsatile flow only) under steady and pulsatile
      flow. It was found that the Doppler power from porcine whole blood under steady
      flow decreased with the speed by approximately 13 dB from 3 to 33 cm/s and was
      only 3 dB higher than that from RBC suspension at 33 cm/s, suggesting minimal RBC
      aggregation in whole blood at this speed. The apparent cyclic variation from
      whole blood was observed at 20 and 40 beats/min (BPM). The cyclic variation
      became more obvious as the speed and stroke rate decreased. The mean Doppler
      power over a cycle increased as the peak speed decreased. The Doppler power
      reached a maximum near peak systole and a minimum at late diastole at the center
      of the tube. This pattern cannot be explained by RBC aggregation due to the shear
      rate alone, and may be attributed to acceleration and deceleration along with
      aggregation. The cyclic variation was not observed at 60 BPM, probably because of
      a lack of time for aggregation to occur.

PMID- 11597367
TI  - Color Doppler detection of acoustic streaming in a hematoma model.
AB  - Accurate differentiation between stagnant blood and soft tissue or clotted and
      unclotted blood has potential value in managing trauma patients with internal
      hemorrhage. Determination by regular ultrasound (US) imaging is sometimes
      difficult because the sonographic appearance of blood, clots and soft tissue may
      be similar. A hematoma model was developed to investigate the use of acoustic
      streaming for hematoma diagnosis in an in vivo environment. The results showed
      that a derated spatial peak temporal average (SPTA) intensity of 30 W/cm(2) was
      needed to generate color-Doppler-detectable streaming in stirred blood. The
      streaming velocity increased in proportion to the derated intensity. Streaming
      was also detected in stagnant blood, but at higher intensities. In clots,
      streaming was not detected even at high intensities. The streaming detection may
      be a valuable tool for improving the distinction between liquid blood and clots
      or soft tissue in hematoma diagnosis.

PMID- 11597368
TI  - On the interaction between ultrasound and contrast agents during Doppler
      investigations.
AB  - Knowledge of interaction mechanisms between ultrasound (US) and contrast agents
      (CA) suspended in blood is important for a correct interpretation of clinical
      investigation results. Experiments performed in different laboratories have shown
      that, as a consequence of primary radiation force, CA tend to move away from the
      US transducer. Accordingly, Doppler spectra produced by particles suspended in
      moving water turn out to be significantly altered from what is theoretically
      expected. The purpose of this paper is twofold. First, an original model
      describing the bubble dynamics as the outcome of the balance between US radiation
      force and fluid drag force is validated for the case in which bubbles are
      suspended in blood. The high fluid viscosity is shown to prevent significant
      bubble deviations from the unperturbed fluid streamlines so that, in large
      vessels, a residual spectral distortion may exist only at the highest intensity
      levels permitted by current regulations. Finally, the relative importance and
      differences between the effect of primary radiation force and streaming
      mechanisms that, in principle, could lead to similar effects, are discussed.

PMID- 11597369
TI  - Elastic properties of tendon measured by two different approaches.
AB  - Elastic properties of tendon were assessed by two different approaches. Six fresh
      bovine Achilles tendon specimens were used. The first approach directly measured
      Young's modulus along the transverse direction (E(perpendicular)) and the
      longitudinal direction (E(parallel)), using a cyclic compression-relaxation
      method. Young's moduli were derived based on the measured strain and stress
      values. The ratio of E(parallel): E(perpendicular) at smaller strains was around
      4 and decreased to 0.6 approximately 1.1 at larger strains. The second approach
      assumed that tendons are transversely isotropic. Three observable second-order
      elastic stiffness constants (c(11), c(13) and c(33)) were obtained by sound speed
      measurements along various propagation directions. The measured elastic stiffness
      constants were also correlated with results from the first approach. It was shown
      that the transverse isotropy assumption was valid at small strains. However, a
      significant discrepancy existed between the two approaches. The discrepancy was
      primarily due to viscoelasticity associated with the first approach.

PMID- 11597370
TI  - Automated edge-detection technique for measurement of brachial artery reactivity:
      a comparison of concordance with manual measurements.
AB  - Concerns have been raised about the reproducibility of brachial artery reactivity
      (BAR), because subjective decisions regarding the location of interfaces may
      influence the measurement of very small changes in lumen diameter. We studied 120
      consecutive patients with BAR to address if an automated technique could be
      applied, and if experience influenced reproducibility between two observers, one
      experienced and one inexperienced. Digital cineloops were measured automatically,
      using software that measures the leading edge of the endothelium and tracks this
      in sequential frames and also manually, where a set of three point-to-point
      measurements were averaged. There was a high correlation between automated and
      manual techniques for both observers, although less variability was present with
      expert readers. The limits of agreement overall for interobserver concordance
      were 0.13 +/- 0.65 mm for the manual and 0.03 +/- 0.74 mm for the automated
      measurement. For intraobserver concordance, the limits of agreement were - 0.07
      +/- 0.38 mm for observer 1 and - 0.16 +/- 0.55 mm for observer 2. We concluded
      that BAR measurements were highly concordant between observers, although more
      concordant using the automated method, and that experience does affect
      concordance. Care must be taken to ensure that the same segments are measured
      between observers and serially.

PMID- 11597371
TI  - On the relationship between power mode and pressure amplitude decorrelation.
AB  - Estimation of mean transit time, along with tissue blood volume, are important
      factors in determining soft tissue perfusion. Recently, power mode decorrelation
      techniques have been successfully used to estimate mean transit time of red blood
      cells or contrast material through a region-of-interest (ROI) both in laminar
      flow phantoms and in vivo. The previously described theory for power mode
      decorrelation derives from a phenomenological stochastic differential equation
      (Langevin equation) based on conservation of matter, relating the detected signal
      power to the measured rate of decorrelation. Given the experimental support for
      power mode decorrelation as a method to estimate mean transit time, it becomes
      important to determine the relationship between the phenomenological parameters
      that appear in the corresponding stochastic equation and system parameters, such
      as the transducer point response function. With this equation as a starting
      point, and using the fact that the pressure amplitude is a Gaussianly distributed
      random process, the following stochastic differential equation for the pressure
      amplitude p(t) is derived, a necessary first step in establishing the
      relationship between the measured decorrelation rate and system parameters (i.e.,
      point response function): dp(t)/dt = -(v/2+2ik x v)p(t)+f(t), where v/2
      represents the rate of decorrelation, 2k x v is the Doppler shift for an
      insonating wave vector k and particle velocity v.f(t) is a stationary, white
      noise Gaussian random process.

PMID- 11597372
TI  - Tofu as a tissue-mimicking material.
AB  - The acoustic properties of one kind of tofu (soft, firm and extra-firm types)
      commercially available in grocery markets were measured. It was found that
      density, speed of sound and attenuation coefficient of tofu were close to those
      of some soft tissues. It is suggested that tofu may serve as a tissue-mimicking
      material for some biomedical ultrasound (US) through transmission applications in
      vitro.

PMID- 11597373
TI  - Studies on supportive care in oral mucositis: random or randomised?

PMID- 11597374
TI  - European Organization for Research and Treatment of Cancer (EORTC) Laboratory
      Research Division workshop on the role of in vivo pre-clinical models in the
      development of contemporary cancer therapeutics, Verona, Italy, 3 February 2001.

PMID- 11597375
TI  - What have we learnt from previous phase II trials to help in the management of
      childhood brain tumours?
AB  - Contrary to major advances in cure rates observed for almost all childhood
      cancers, progress in reducing brain tumour survival rates remains very limited.
      Although new drug development in oncology is founded on principles outlined in
      the organised methodology of phase I, II, and III trials, based on rigorous study
      design using standardised criteria, this approach has been applied very slowly in
      the field of neuro-oncology. There are multiple explanations for the paucity of
      well-conducted prospective clinical trials, such as the rarity and the
      heterogeneity of these tumours, and the reluctance of some investigators to
      enroll their patients in constraining trials. Data from the past two decades
      shows that several methodological problems preclude the drawing of any definite
      conclusions for the majority of drugs assessed. Among them, the necessity of a
      central neuropathological and neuroradiological review has been highlighted in,
      at least, two multicentric studies. Changes in histological diagnosis and grade
      have been reported in a proportion as high as 20%, and changes in response rate
      in 14% of the cases. This review of phase II trials for brain tumours reveals a
      wide array of sometimes arbitrary response definitions, that is if response is
      defined at all, and most series have enrolled small numbers of patients. We
      report on the different problems encountered in childhood brain tumours in these
      phase II trials, and their impact on phase III trials.

PMID- 11597376
TI  - Decrease of duration and symptoms in chemotherapy-induced oral mucositis by
      topical GM-CSF: results of a prospective randomised trial.
AB  - We have conducted a prospective controlled randomised clinical study testing for
      the efficacy of topical GM-CSF (molgramostim), as compared to the combined
      topical use of an antiseptic agent (povidone-iodine) and amphotericin B (AA) in
      patients with chemotherapy-induced mucositis World Health Organization (WHO)
      grades I-III. 31 patients (17 females, 14 males) developing oral mucositis
      following the administration of 5-fluorouracil (5-FU)-based chemotherapy were
      entered into the present trial. 15 patients were randomised to receive GM-CSF
      mouthwashes, whereas 16 patients were randomised into the control arm to receive
      AA. Reported history (P=0.6109) and grading of oral mucositis (2.1+/-0.7,
      respectively; P=0.9867) were balanced and equally distributed between the two
      groups. The mean size of lesions of oral mucositis was 1.5+/-0.6 cm (range: 0.7
      2.5 cm) in the GM-CSF group and 1.2+/-0.5 cm (range: 0.5-2.5 cm) in the AA group
      (P=0.08), respectively. The mean number of oral mucositis lesions was 1.9+/-1.1
      (range: 1-4) in the GM-CSF group and 2.1+/-1.2 (range: 1-4) in the AA group
      (P=0.63), respectively. None of the patients had previously received colony
      stimulating factors either topically or systemically. Treatment for oral
      mucositis was initiated on day 2.7+/-1.2 (range: day 1-8) after onset of symptoms
      in the GM-CSF group and on day 1.8+/-1.4 (range: day 1-3; P=0.11) in the AA
      group. The topical application of GM-CSF resulted in a significantly shorter
      duration and quicker resolution of oral mucositis, as compared to AA including
      both, pretreatment plus treatment periods (5.3+/-2.5 versus 8.1+/-1.5 days;
      P=0.0008) as well as the necessary duration of treatment needed until complete
      remission of lesions (2.8+/-0.7 versus 6.3+/-1.1 days; P<0.0001). A systemic
      effect of topical GM-CSF upon the number of peripheral blood leukocytes or
      granulocytes was excluded. We conclude that the topical application of GM-CSF by
      mouthwash significantly abbreviated the duration and relieved patients from
      symptoms of chemotherapy-induced mucositis and was superior to the topical
      application of AA.

PMID- 11597377
TI  - Local application of granulocyte-macrophage colony stimulating factor (GM-CSF)
      for the treatment of oral mucositis.
AB  - The combination of radiation and chemotherapy administered for patients
      undergoing therapy for advanced head and neck neoplasms leads to a significant
      rise in toxic side-effects. Oral mucositis remains one of the most distressing
      factors leading to pain, impairment of oral nutrition, local and systemic
      infection and often cessation of the oncological treatment. The local and
      systemic administration of recombinant growth factors has revealed a potential
      benefit in the treatment of oral mucositis. Clinical data concerning the topical
      use of granulocyte-macrophage colony-stimulating-factor (GM-CSF) in the
      prevention and therapy of mucositis in patients undergoing radiochemotherapy for
      advanced cancer of the head and neck are presented in this paper. A prospective,
      randomised, open parallel-grouped, single centre study at a university hospital
      was performed. 35 patients with stage III and IV carcinomas of the head and neck
      were included. Statistical analysis concerning the degree of oral mucositis, the
      perception of pain, the incidence of secondary infections and the change in
      haematological parameters revealed no superiority of GM-CSF in comparison to
      conventional mouthwash between the two groups of patients. As a result, and faced
      with the tremendous costs of the regular use of a recombinant cytokine, we ended
      the clinical trial after 35 patients. The topical administration of GM-CSF to
      treat oral mucositis as a result of radiochemotherapy in patients suffering from
      head and neck cancer cannot be recommended.

PMID- 11597378
TI  - Double-blind, placebo-controlled cross-over study of oral pilocarpine for the
      prevention of chemotherapy-induced oral mucositis in adult patients with cancer.
AB  - This study aimed to investigate the effect of oral pilocarpine (OP) in reducing
      the incidence of chemotherapy-induced oral mucositis. 32 adult cancer patients
      completed a total of 82 courses of chemotherapy in which either OP or placebo was
      given prophylactically in a double-blind cross-over design to prevent mucositis.
      Mucositis was documented in 20 out of 41 courses in which patients were given
      placebo, whereas mucositis was documented in only six out of 41 courses when
      patients were given OP (P<0.005). OP treatment was found to significantly reduce
      the mucositis score when assessed by the method of Donnelly and colleagues
      (Donnelly JP, Muus P, Schattenberg A, De Witte T, Horrevorts A, De Pauw BE. Bone
      Marrow Transplant 1992, 9, 409-413). Using this score, all patients scored a
      total of 52 when they were given the placebo versus eleven when they were treated
      with OP (P<0.001). A similar reduction in mucositis score was noticed using the
      World Health Organization (WHO) mucositis score; the total patient score was 25
      for the placebo-treated group versus 6 for the OP group (P<0.001). We therefore
      conclude that oral pilocarpine is highly effective in the prevention of oral
      mucositis when given prophylactically to adult patients receiving a variety of
      cancer chemotherapy regimens.

PMID- 11597379
TI  - Phase II study of pegylated liposomal doxorubicin (Caelyx) as induction
      chemotherapy for patients with squamous cell cancer of the head and neck.
AB  - A phase II trial of pegylated liposomal doxorubicin (Caelyx) as induction
      chemotherapy was conducted in 20 patients with treatment-naive squamous cell
      cancer of the head and neck (SCCHN). 10 patients received two cycles of Caelyx
      (40 mg/m(2)) every 3 weeks before starting radical radiotherapy (RT).
      Subsequently, consecutive groups of 3 patients received a third escalating dose
      of Caelyx (10, 15 and 20 mg/m(2)) 3 days before RT. 9 of 18 (50%, 95% confidence
      intervals (CI): 26-74%) evaluable patients responded to Caelyx, with 11 responses
      in 26 (42%, 95% CI: 24-62%) evaluable sites (three complete responses (12%),
      eight partial responses (31%)). There was no grade 3/4 haematological, mucosal or
      cardiac toxicity. Nausea and vomiting were minimal. There were no drug-related RT
      delays. Local RT-induced toxicity was not increased. Caelyx has significant
      activity against SCCHN and warrants further investigation in this disease. In
      view of its tumour targeting properties and activity at moderate doses, it may be
      useful in concomitant chemoradiotherapy strategies for SCCHN.

PMID- 11597380
TI  - A hypothesis about tumour development and the clinical features of hereditary
      breast cancers.
AB  - A unifying hypothesis is presented about tumour biology in hereditary breast
      cancer in relation to the epithelial origin and the degree of differentiation of
      the normal epithelium at the time of tumour initiation. By using different breast
      cancer syndromes as examples, it is possible to, at least partly, predict the
      tumour biology, clinical presentation and therapeutic response.

PMID- 11597381
TI  - Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of
      the Rizzoli's 4th protocol.
AB  - From January 1993 to March 1995, 162 patients with osteosarcoma of extremities
      were treated according to the IOR/OS-4 protocol. 133 patients had localised
      disease, while 29 had metastases at diagnosis. These last patients were
      simultaneously operated upon for their primary and metastatic lesions.
      Chemotherapy consisted preoperatively of two cycles of high dose methotrexate
      (HDMTX) and one cycle each of cisplatin (CDP)-doxorubicin (ADM), CDP/ifosfamide
      (IFO) and IFO/ADM. After surgery, patients were treated with the aforementioned
      drugs used as single agents. The mean follow-up of all patients was 6.5 years
      (5.5-8 years). Surgery was a limb salvage in 94% of cases, and the 5-year event
      free survival (EFS) and overall survival (OS) rates were 56 and 71% for patients
      with localised disease, and 17 and 24% for patients with metastases at diagnosis.
      These results did not differ from those achieved in our previous study (IOR/OS-3)
      in which IFO was used only postoperatively in poor responders.

PMID- 11597382
TI  - Ovarian carcinoma cells in serous effusions show altered MMP-2 and TIMP-2 mRNA
      levels.
AB  - The expression of matrix metalloproteinases (MMP) and their inhibitor TIMP-2 in
      serous effusions from patients with ovarian carcinoma and its association with
      clinico-pathological parameters were analysed. The findings in carcinoma cells in
      effusions were compared with corresponding primary and metastatic lesions. Sixty
      six effusions and 96 tissue sections were stained for MMP-1, MMP-2 and MMP-9
      applying immunohistochemistry (IHC) and analysed for MMP-2, MMP-9 and TIMP-2
      expression using mRNA in situ hybridisation (ISH). MMP-2 and MMP-9 mRNA levels in
      30 effusions were subsequently analysed using reverse transcription- polymerase
      chain reaction (RT-PCR). MMP and TIMP expression was detected in both carcinoma
      and mesothelial cells in effusions. The levels were consistently higher in
      malignant cells, significantly so for MMP-1 (P=0.016) and MMP-2 (P=0.036)
      proteins, as well as for TIMP-2 mRNA (P=0.008). In tissue sections, MMP-1, MMP-2
      and MMP-9 protein expression was mostly localised to tumour cells, while MMP-2,
      MMP-9 and TIMP-2 mRNA were predominantly detected in stromal cells.
      Adenocarcinoma cells in effusions showed a significant upregulation of MMP-2
      expression compared with primary tumours, with a concomitant downregulation of
      TIMP-2. RT-PCR demonstrated the presence of MMP-2 and MMP-9 in 28/30 and 0/30
      specimens, respectively. MMP and TIMP are thus mainly synthesised by cancer cells
      in effusions, while stromal cells have a similar role in solid tumours. MMP-1 and
      MMP-2 production predominates over that of MMP-9 in effusions. Increased MMP-2
      and reduced TIMP-2 levels are seen in ovarian carcinoma cells in effusions,
      possibly marking the acquisition of a metastatic phenotype.

PMID- 11597383
TI  - Preoperative chemoradiation with raltitrexed ('Tomudex') for T2/N+ and T3/N+
      rectal cancers: a phase I study.
AB  - The use of raltitrexed ('Tomudex') as concomitant chemotherapy during
      preoperative radiotherapy in chemonaive patients with stage II/III rectal cancer
      has been examined in this study and its recommended dose in conjunction with
      radiotherapy investigated. Forty-five Gray (Gy) of radiotherapy (1.8 Gy daily, 5
      days per week) was delivered to the posterior pelvis, followed by a 5.4 Gy boost.
      Single doses of raltitrexed (2.0, 2.5 and 3.0 mg/m(2)) were administered on days
      1, 19 and 38. Only 1 of the 15 patients entered experienced a dose limiting
      toxicity (DLT) (grade 3 leucopenia) at the 3.0 mg/m(2) dose level. The overall
      response rate was 80% (five complete responses, seven partial responses). These
      preliminary data suggest that raltitrexed is a well tolerated and effective
      treatment when combined with preoperative radiotherapy in patients with stage
      II/III rectal cancer. The recommended dose of raltitrexed for future phase II
      studies will be 3.0 mg/m(2).

PMID- 11597384
TI  - Evaluation of an oral care protocol intervention in the prevention of
      chemotherapy-induced oral mucositis in paediatric cancer patients.
AB  - Oral mucositis is the most frequent and severe complication of chemotherapy in
      children with cancer that can aggravate the child's clinical condition and
      increase the risk of infection. This prospective comparative study was designed
      to determine the effectiveness of a preventive oral care protocol in reducing
      chemotherapy-induced oral mucositis in children with cancer. During an 8-month
      period, 42 children aged 6 to 17 years with haematological malignancies or solid
      tumours were evaluated. The 21 children who were included in the first 4-month
      period of the study constituted the control group. Another 21 children were
      enrolled in the subsequent 4 months and were assigned to the experimental group,
      in which they were given an oral care protocol intervention. The oral care
      protocol consisted of tooth brushing, 0.2% chlorhexidine mouth rinse and 0.9%
      saline rinse. Children in both groups were evaluated twice a week for 3 weeks.
      The incidence of ulcerative lesions, severity of oral mucositis and the related
      pain intensity were used as the main outcome variables. A 38% reduction in the
      incidence of ulcerative mucositis was found in children using the oral care
      protocol compared with children in the control group. The severity of oral
      mucositis (P=0.000002) and the related pain (P=0.0001) were significantly reduced
      with the intervention. These results support the preventive use of the oral care
      protocol in paediatric cancer patients who undergo chemotherapy for cancer
      treatment.

PMID- 11597385
TI  - Angiogenic profile of childhood primitive neuroectodermal brain
      tumours/medulloblastomas.
AB  - Primitive neuroectodermal brain tumours (PNET) including medulloblastomas
      (PNET/MB) are the most common malignant brain tumours of childhood. Similar to
      many other brain tumours, PNET/MB often show marked neovascularisation. To
      determine which angiogenic factors contribute to PNET/MB angiogenesis, we
      examined the expression of eight angiogenic factors (vascular endothelial growth
      factors (VEGF, VEGF-B, VEGF-C), basic fibroblast growth factor (bFGF),
      angiopoetins (Ang-1, Ang-2), transforming growth factor (TGF-alpha), and platelet
      derived endothelial growth factor (PDGF-A)) by semi-quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) in six PNET cell lines and 28
      primary PNET/MB. Expression levels of angiogenic factors were compared with
      microvessel density, TrkC mRNA expression, clinical variables and survival
      outcomes. Our results indicate that all PNET/MB tested produce a wide range of
      angiogenic factors that are, individually or together, likely to play a direct
      role in PNET/MB tumour growth. This suggests that anti-angiogenesis approaches
      targeting VEGF alone may be insufficient in PNET/MB.

PMID- 11597387
TI  - Second tumours.

PMID- 11597388
TI  - Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in
      517 Dutch breast and/or ovarian cancer families.
AB  - In 517 Dutch families at a family cancer clinic, we screened for BRCA1/2
      alterations using the Protein Truncation Test (PTT) covering approximately 60% of
      the coding sequences of both genes and direct testing for a number of previously
      identified Dutch recurrent mutations. In 119 (23%) of the 517 families, we
      detected a mutation in BRCA1 (n=98; 19%) or BRCA2 (n=21; 4%). BRCA1/2 mutations
      were found in 72 (52%) of 138 families with breast and ovarian cancer (HBOC), in
      43 (13%) of the 339 families with breast cancer only (HBC), in 4 (36%) of 11
      families with ovarian cancer only (HOC), and in nine of 29 families with one
      single young case (<40 years) of breast cancer. Between the different subgroups
      of families (subdivided by the number of patients, cancer phenotype and age of
      onset) the proportion of BRCA1/2 mutations detected, varied between 6 and 82%.
      Eight different mutations, each encountered in at least six distinct families,
      represented as much as 61% (73/119 families) of all mutations found. The original
      birthplaces of the ancestors of carriers of these eight recurrent mutations were
      traced. To estimate the relative contribution of two important regional recurrent
      mutations (BRCA1 founder mutation IVS12-1643del3835 and BRCA2 founder mutation
      5579insA) to the overall occurrence of breast cancer, we performed a population
      based study in two specific small regions. The two region-specific BRCA1 and
      BRCA2 founder mutations were detected in 2.8% (3/106) and 3.2% (3/93) of the
      unselected breast tumours, respectively. Of tumours diagnosed before the age of
      50 years, 6.9% (3/43) and 6.6% (2/30) carried the region-specific founder
      mutation. Thus, large regional differences exist in the prevalence of certain
      specific BRCA1/BRCA2 founder mutations, even in very small areas concerning
      populations of approximately 200000 inhabitants.

PMID- 11597389
TI  - Dietary fibre and the risk of colorectal cancer.
AB  - The relationship between various types of fibre and colorectal cancer risk was
      investigated using data from a case-control study conducted in the Swiss Canton
      of Vaud between January 1992 and December 2000. The study included 286 cases of
      incident, histologically-confirmed colorectal cancers (149 colon and 137 rectal
      cancers) admitted to the University Hospital of Lausanne, and 550 controls whose
      admission diagnosis was of acute, non-neoplastic diseases. Dietary habits were
      investigated using a validated food frequency questionnaire (FFQ). Odds ratios
      (ORs) were computed after allowance for age, sex, education, physical activity
      and energy intake. Fibre was analysed both as a continuous variable and in
      tertiles. There was a significant inverse relationship of total fibre intake
      (determined by the Englyst method as non-starch polysaccharides) and of its
      components with the risk of colorectal cancer. ORs for a difference in intake of
      one standard deviation from the mean fibre intake of the control distribution was
      0.57 for total fibres, 0.55 for soluble non-cellulose polysaccharides (NCPs),
      0.58 for total insoluble fibres, 0.57 for cellulose, 0.62 for insoluble NCP and
      0.62 for lignin. When fibre was classified according to its source, the OR was
      0.60 for vegetables, 0.78 for fruit and 0.74 for grain fibre. The ORs were
      similar for colon and rectal cancer and consistent across the strata of the major
      covariates and of several types of fibres.

PMID- 11597390
TI  - Tumour-associated antigen (TAA)-specific cytotoxic T cell (CTL) response in vitro
      and in a mouse model, induced by TAA-plasmids delivered by influenza virosomes.
AB  - We investigated influenza virosomes as a TAA-gene delivery system for use in TAA
      directed anti-cancer vaccine therapy. An engineered plasmid (GC90) expressing the
      parathyroid hormone-related peptide (PTH-rP), a protein secreted by prostate and
      lung carcinoma cells, was included in influenza virosomes (GC90V). The ability of
      GC90V to elicit a PTH-rP-specific cytotoxic T cell (CTL) response was
      demonstrated in BALB/c mice immunised with intranasal (i.n.) GC90V+/-adjuvant
      subcutaneous (s.c.) interleukin-2 (IL-2). A PTH-rP-specific CTL response with
      antitumour activity was also demonstrated in human peripheral blood mononuclear
      cells (PBMC) stimulated in vitro with GC90V infected autologous dendritic cells
      (DC). These results provide a rationale for investigating GC90V in clinical
      trials of anticancer vaccine therapy.

PMID- 11597391
TI  - Chemopreventive allylthiopyridazine derivatives induce apoptosis in SK-Hep-1
      hepatocarcinoma cells through a caspase-3-dependent mechanism.
AB  - Dietary organosulphur compounds including diallylsulphide, a component of garlic
      oil, were shown to inhibit the proliferation of tumour cells. Since
      hepatocellular carcinoma is one of the most lethal malignancies and there is no
      effective preventive measure to date, we wished to pursue the chemopreventive
      potential of the synthetic allylthiopyridazine derivatives (K compounds) on
      hepatocarcinoma cells. Here, we report that the K compounds efficiently inhibited
      SK-Hep-1 cell proliferation through induction of apoptosis. Increased chain
      length at the 3-position of allylthiopyridazine ring improved the potency of
      growth inhibition. K compounds downregulated Bcl-2, while Bax remained unchanged,
      reducing the ratio of Bcl-2 to Bax. We also provide evidence that the K compound
      induced apoptosis involves cytochrome c release and caspase-3 activation. These
      results suggest that the allythiopyridazine derivatives, especially 3-propoxy-6
      allylthiopyridazine, induce apoptosis in SK-Hep-1 cells through a caspase-3
      dependent mechanism, which may contribute to the chemopreventive function for
      hepatocellular carcinoma.

PMID- 11597392
TI  - Expression of vascular endothelial growth factor in mouse tumours subjected to
      photodynamic therapy.
AB  - The aim of this study was to define the appropriate fractionation interval
      between photodynamic therapy (PDT) for the enhancement of its anti-tumour
      effects. Tumour reoxygenation and the kinetics of tumour vascular cells following
      PDT were evaluated in mice by means of immunohistochemical staining for the
      vascular endothelial growth factor (VEGF) and the proliferating cell nuclear
      antigen (PCNA), respectively. The VEGF labelling indices (LIs) of the tumour
      cells and the PCNA LIs of the tumour vascular cells were assessed at various time
      intervals after PDT. The tumour cell VEGF LIs of the experimental groups at time
      points from 0 to 6 h after PDT were significantly higher than those of the
      control groups, but subsequently returned to control levels at 24 h after PDT.
      The vascular cell PCNA LI of the experimental group at 24 h after PDT was
      significantly lower than that of the control group, but returned to the control
      level at 48 h. These results indicated that the tumour subjected to PDT might be
      reoxygenated, and that the maximum damage to the tumour vasculature emerged at 24
      h after PDT. We propose here that the fractionation interval between PDTs should
      be 24 h.

PMID- 11597393
TI  - An evolutionary-game model of tumour-cell interactions: possible relevance to
      gene therapy.
AB  - Evolutionary games have been applied as simple mathematical models of populations
      where interactions between individuals control the dynamics. Recently, it has
      been proposed to use this type of model to describe the evolution of tumour cell
      populations with interactions between cells. We extent the analysis to allow for
      synergistic effects between cells. A mathematical model of a tumour cell
      population is presented in which population-level synergy is assumed to originate
      through the interaction of triplets of cells. A threshold of two cooperating
      cells is assumed to be required to produce a proliferative advantage. The
      mathematical behaviour of this model is explored. Even this simple synergism
      (minor clustering effect) is sufficient to generate qualitatively different cell
      population dynamics from the models published previously. The most notable
      feature of the model is the existence of an unstable internal equilibrium
      separating two stable equilibria. Thus, cells of a malignant phenotype can exist
      in a stable polymorphism, but may be driven to extinction by relatively modest
      perturbations of their relative frequency. The proposed model has some features
      that may be of interest to biological interpretations of gene therapy. Two
      prototypical strategies for gene therapy are suggested, both of them leading to
      extinction of the malignant phenotype: one approach would be to reduce the
      relative proportion of the cooperating malignant cell type below a certain
      critical value. Another approach would be to increase the critical threshold
      value without reducing the relative frequency of cells of the malignant
      phenotype.

PMID- 11597394
TI  - Rapamycin increases the cellular concentration of the BCL-2 protein and exerts an
      anti-apoptotic effect.
AB  - The immunosuppressant rapamycin, an immunophilin-binding antibiotic, has been
      studied in follicular B-cell lymphoma lines that express the highest level of the
      BCL-2 protein. The growth rate of human follicular B-cell lymphoma lines was
      slowed more efficiently than that of other human B-cell lines or non-B-cell
      lines. This effect was dependent on the arrest of cells in the G(1) phase; the
      number of apoptotic cells was not increased. Rapamycin inhibited apoptosis or
      caspase activation induced by cytotoxic drugs, whereas caspase activation by
      doxorubicin was not inhibited. The increase in the cellular concentration of BCL
      2 protein was related to its concentration in the steady state and was unrelated
      to the amount of bcl-2 mRNA. The increase of BCL-2 level in the cells rather than
      its level in the steady state may be important for drug resistance. The
      biochemical target of rapamycin, the mTOR kinase, may be a candidate sensitising
      agent for chemotherapy. This effect of rapamycin shows that G(1) arrest and
      protection from apoptosis are combined events susceptible to regulation by
      pharmacological means.

PMID- 11597396
TI  - Something old, something new, something hot, something blue.

PMID- 11597395
TI  - A novel gene on human chromosome 2p24 is differentially expressed between
      androgen-dependent and androgen-independent prostate cancer cells.
AB  - Identification of genes involved in the transition from androgen-dependent to
      androgen-independent prostate cancer is important to extend our current knowledge
      of the disease. Using differential display RT-PCR analysis between androgen
      dependent and androgen-independent prostate cancer cells, we have identified a
      novel gene, designated GC109. GC109 harbours a putative Cys-His cluster, a
      nuclear localisation signal, a leucine zipper and a ret finger protein (rfp)-like
      domain. GC109 mRNA expression in normal human tissues was found not to be
      restricted to the prostate. However, using a variety of 15 human cancer cell
      lines, GC109 mRNA was preferentially expressed in androgen-dependent LNCaP-FGC,
      compared with androgen-independent LNCaP-LNO, DU145 and PC3 human prostate cancer
      cells. Finally, the GC109 gene was mapped on human chromosome 2p24. Based on its
      protein domain structure and chromosomal localisation, we hypothesise that GC109
      may be involved in chromosomal rearrangements in prostate cancer.

PMID- 11597397
TI  - Introduction. EGFR in tumour growth: biological role and clinical implications.

PMID- 11597398
TI  - The EGFR family and its ligands in human cancer. signalling mechanisms and
      therapeutic opportunities.
AB  - Growth factors and their transmembrane receptor tyrosine kinases play important
      roles in cell proliferation, survival, migration and differentiation. One group
      of growth factors, comprising epidermal growth factor (EGF)-like proteins and
      neuregulins, stimulates cells to divide by activating members of the EGF receptor
      (EGFR) family, which consists of the EGFR itself and the receptors known as HER2
      4. This highly conserved signalling module plays a fundamental role in the
      morphogenesis of a diverse spectrum of organisms, ranging from humans to
      nematodes, and has also been implicated in the development and growth of many
      types of human tumour cells. In humans, more than 30 ligands and the EGFR family
      of four receptors lie at the head of a complex, multi-layered signal-transduction
      network. Different activated receptor-ligand complexes vary in both the strength
      and type of cellular responses that they induce. Analysis of the multiple
      processes that modulate EGFR signal transduction, such as receptor
      heterodimerisation and endocytosis, has revealed new therapeutic opportunities
      and elucidated mechanisms contributing to the efficacy of existing anticancer
      treatments.

PMID- 11597399
TI  - EGFR and cancer prognosis.
AB  - Elevated levels of the epidermal growth factor receptor (EGFR), a growth-factor
      receptor tyrosine kinase, and/or its cognate ligands have been identified as a
      common component of multiple cancer types and appear to promote solid tumour
      growth. This article examines the relationship between EGFR expression and cancer
      prognosis based on literature compiled on PubMed between 1985 and September 2000.
      More than 200 studies were identified that analysed relapse-free-interval or
      survival data directly in relation to EGFR levels in over 20000 patients.
      Analysis of the data showed that 10 cancer types both express elevated levels of
      EGFR relative to normal tissues and have been studied in sufficient depth to
      allow sound judgements to be made concerning the association between EGFR and
      patient outlook. The EGFR was found to act as a strong prognostic indicator in
      head and neck, ovarian, cervical, bladder and oesophageal cancers. In these
      cancers, increased EGFR expression was associated with reduced recurrence-free or
      overall survival rates in 70% (52/74) of studies. In gastric, breast, endometrial
      and colorectal cancers, the EGFR provided more modest prognostic information,
      correlating to poor survival rates in 52% (13/25) of studies, while in non-small
      cell lung cancer (NSCLC), EGFR expression only rarely (3/10 studies) related to
      patient outlook. However, it is likely that the true prognostic significance of
      the EGFR has been underestimated as the published studies only assessed total
      cellular EGFR levels, rather than the activated form of the receptor, and were
      not standardised with regard to patient populations or assay methods. Finally, it
      is important to stress that failure to detect a prognostic significance for EGFR
      in any one cancer type does not necessarily preclude patients from benefiting
      from anti-EGFR therapies.

PMID- 11597400
TI  - The EGFR as a target for anticancer therapy--focus on cetuximab.
AB  - The anti-epidermal-growth-factor-receptor (EGFR) monoclonal antibody cetuximab
      specifically binds to the EGFR with high affinity, blocking growth-factor
      binding, receptor activation and subsequent signal-transduction events leading to
      cell proliferation. Preclinical studies, both in vitro and in vivo, have shown
      that cetuximab enhances the antitumour effects of chemotherapy as well as
      radiotherapy by inhibiting cell proliferation, angiogenesis and metastasis and by
      promoting apoptosis. As of June 2000, 526 patients with advanced solid tumours
      were treated with cetuximab in phase I/II clinical trials. Analysis of the
      results of three phase I trials showed that cetuximab has non-linear
      pharmacokinetics, with saturation of drug-elimination pathways occurring at doses
      between 200 and 400 mg/m(2). Adverse-event data for 239 patients across most of
      the completed or ongoing phase I-III trials indicated that the antibody was
      generally well tolerated. Cetuximab has been evaluated both alone and in
      combination with radiotherapy and various cytotoxic chemotherapeutic agents in a
      series of phase I/II studies that primarily treated patients with either head and
      neck or colorectal cancer. Although not a primary objective of these studies,
      clinical responses to cetuximab were observed in many patients who had previously
      failed chemotherapy and/or radiotherapy or were otherwise unlikely to achieve a
      therapeutic outcome. Based on these promising results, additional phase II and
      phase III trials are currently underway in head and neck and colorectal cancer.

PMID- 11597401
TI  - Synthesis and antiinflammatory, analgesic activity of 3,3'-(1,2-ethanediyl)-bis[2
      aryl-4-thiazolidinone] chiral compounds. Part 10.
AB  - In this note, the synthesis and structure-activity relationships of a new series
      of 2R,2'R/2S,2'S and 2R,2'S-meso 3,3'-(1,2-ethanediyl)-bis[2-aryl-4
      thiazolidinones] are described. Antiinflammatory activity was investigated by the
      carrageenin-induced paw edema test and analgesic activity by acetic acid writhing
      and hot plate tests in rats. All compounds displayed ulcerogenic effects and
      acute toxicity much lower than indomethacin and phenylbutazone. Meso isomers (b)
      showed better pharmacological profiles than corresponding racemates (a). Methoxy
      substitution patterns of the aryls on stereogenic carbons are generally the most
      favorable on the pharmacological profile.

PMID- 11597402
TI  - Studies on 3-deoxy-D-manno-octulosonic acid 8-phosphate synthase using chorismate
      mutase inhibitors.
AB  - The proposed cyclic mechanism of 3-deoxy-D-manno-octulosonic acid 8-phosphate
      synthase and the mechanism of chorismate mutase share certain structural and
      electronic similarities. In this report, we examine several inhibitors of
      chorismate mutase for their efficacy against KDO 8-P synthase.

PMID- 11597403
TI  - Antiviral drug design: computational analyses of the effects of the L100I
      mutation for HIV-RT on the binding of NNRTIs.
AB  - Monte Carlo/free energy perturbation (MC/FEP) calculations were used to evaluate
      the binding free energy change for HIV-RT/inhibitor complexes upon L100I
      mutation. Inhibitor size and flexibility adjacent to hydrogen-bonding sites are
      evident as important considerations for antiviral drug design.

PMID- 11597404
TI  - Amino acid phosphoramidate nucleosides: potential ADEPT/GDEPT substrates.
AB  - A series of aromatic, serum-stable, water soluble and nontoxic amino acid
      phosphoramidate monoesters of 5-fluoro-2'-deoxyuridine (FUdR) and 1-beta
      arabinofuranosylcytosine (Ara-C) was shown to inhibit the cellular growth of the
      human leukemia cell line CCRF-CEM in the presence of human prostatic acid
      phosphatase (hPAP).

PMID- 11597405
TI  - 3-D-QSAR/CoMFA and recognition models of benzimidazole derivatives at the 5-HT(4)
      receptor.
AB  - 3-D-QSAR/CoMFA methodology and computational simulation of ligand recognition
      have been successfully applied to explain the binding affinities of a series of
      benzimidazole derivatives 1-24 acting at serotonin 5-HT(4)Rs. Both derived
      computational models have facilitated the identification of the structural
      elements of the ligands that are key to high 5-HT(4)R affinity. The results
      provide the tools for predicting the affinity of related compounds, and for
      guiding the design and synthesis of new ligands with predetermined affinities and
      selectivity.

PMID- 11597406
TI  - Use of 2-(tert-butyldiphenylsilyloxymethyl) benzoyl as N-protecting group for the
      synthesis of prooligonucleotides.
AB  - A short TCCT Me-SATE prooligonucleotide was successfully synthesized using 2
      (tert-butyldiphenyloxymethyl) benzoyl protecting group, after its removal by
      means of trimethylsilyl chloride and water.

PMID- 11597407
TI  - Design, synthesis, and biological activity of diiminoisoindolines as complement
      component 3a antagonists.
AB  - The failure to fully regulate the inflammation response has been linked to
      diseases such as rheumatoid arthritis, septic shock syndrome, and asthma. The
      human complement system initiates and regulates the inflammation response through
      a cascade of regulatory factors. Complement Component 3a (C3a) is an essential
      regulatory factor and inhibiting its binding to a C3a receptor will diminish the
      inflammation response by disrupting the cascade. We report the design, synthesis,
      in vitro and in vivo activity of diiminoisoindolines as C3a antagonists.

PMID- 11597408
TI  - A designed antagonist of the thyroid hormone receptor.
AB  - We synthesized an analogue of the thyromimetic GC-1 bearing the same hydrophobic
      appendage as the estrogen receptor antagonist ICI-164,384. While having reduced
      affinity for the thyroid hormone receptors compared to GC-1, it behaves in a
      manner consistent with a competitive antagonist in a transactivation assay.

PMID- 11597409
TI  - Glu375Gln and Asp225Val mutants: about the nature of the covalent linkages
      between heme group and apo-Protein in bovine lactoperoxidase.
AB  - In analogy with studies previously reported for myeloperoxidase (Kooter, I. M.;
      Moguilevsky, N.; Bollen, A.; Van der Veen, L. A.; Otto, C.; Dekker, H. L.; Wever,
      R. J. Biol. Chem. 1999, 274, 26794), we examined for bovine lactoperoxidase the
      effect of mutation of Asp225 and Glu375, the residues thought to be responsible
      for the covalent binding of the heme group to the apoprotein. Starting from the
      plasmid encoding rbLPO (Watanabe, S.; Varsalona, F.; Yoo, Y.; Guillaume, J. P.;
      Bollen, A.; Shimazaki, K.; Moguilevsky, N. FEBS Letters 1998, 441, 476), which
      was engineered to carry mutations in correspondence of those residues, the
      mutants Asp225Val and Glu375Gln were expressed in CHO cells and their products
      purified and characterized. Unequivocal evidence about the existence of ester
      linkages as well as their relative contribution to the specific spectroscopic and
      catalytic properties of bLPO is here discussed.

PMID- 11597410
TI  - Synthesis and characterisation of a new amphotericin B-methoxypoly(ethylene
      glycol) conjugate.
AB  - The reaction of methoxypoly(ethylene glycol)-4-nitrophenyl carbonate with
      amphotericin B has been used to prepare a new conjugate of amphotericin B (mPEG
      AmB). A preliminary screening of in vitro antifungal activity has suggested that
      mPEG-AmB possesses a similar effect and a similar spectrum of activity as the
      conventional amphotericin B formulated with sodium desoxycholate.

PMID- 11597412
TI  - Novel (4-piperazin-1-ylquinolin-6-yl) arylsulfonamides with high affinity and
      selectivity for the 5-HT(6) receptor.
AB  - The discovery of (4-piperazin-1-ylquinolin-6-yl) arylsulfonamides and their
      binding affinities for a selection of 5-HT and dopamine subreceptors is
      described. Many compounds show high affinity (pK(i)>8) for the 5-HT(6) receptor
      and >100-fold selectivity against a range of other receptors. Structure-activity
      relationships of these compounds are discussed.

PMID- 11597411
TI  - Synthesis, crystal structure determination, and biological properties of the DNA
      dependent protein kinase (DNA-PK) inhibitor 3-cyano-6-hydrazonomethyl-5-(4
      pyridyl)pyrid-[1H]-2-one (OK-1035).
AB  - The first reported synthesis of the DNA-PK inhibitor 3-cyano-6-hydrazonomethyl-5
      (4-pyridyl)pyrid-[1H]-2-one (OK-1035) is described. The structure of OK-1035 was
      validated by X-ray crystallography. An IC(50) value of 100 microM was determined
      for inhibition of DNA-PK, and this is approximately 12-fold higher than that
      reported previously.

PMID- 11597413
TI  - Design and synthesis of a novel class of histone deacetylase inhibitors.
AB  - Histone deacetylase inhibitors (HDACs) have emerged as a novel class of
      antiproliferative agents. Utilizing structure-based design, the synthesis of a
      series of sulfonamide hydroxamic acids is described. Further optimization of this
      series by substitution of the terminal aromatic ring yielded HDAC inhibitors with
      good in vitro and in vivo activities.

PMID- 11597414
TI  - Potent, low molecular weight thrombin receptor antagonists.
AB  - Several benzimidazole derivatives have been identified as potent thrombin
      receptor (PAR-1) antagonists as represented by compound 1h, which showed an
      IC(50) of 33 nM.

PMID- 11597415
TI  - Synthesis and In vitro binding affinities of 1-azabicyclic compounds as
      muscarinic ligands.
AB  - Two series of compounds, 2 and 3, were synthesized and their binding affinities
      were evaluated for the human recombinant muscarinic M(1) receptor subtype
      expressed in CHO cells. Comparing their binding affinities for the NMS binding
      sites and the Oxo-M binding sites, they were assumed as agonists. In particular,
      compound 2e was a good ligand for the agonist binding sites with an IC(50) of 23
      nM, which represents over 1585 times stronger binding than for the antagonist
      binding sites.

PMID- 11597416
TI  - Synthesis of the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1
      c][1,4]benzodiazepine dimer.
AB  - We report the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1
      c][1,4]benzodiazepine (PBD) dimer 16 synthesised through a new and efficient
      route, thus establishing that C2-C3-endo unsaturation enhances both cytotoxicity
      and DNA-binding affinity in A-Ring-linked PBD dimers but to a lesser extent than
      C2/C2'-exo-unsaturation. This new route has allowed the preparation of multi-gram
      quantities of the related clinical candidate 1 and should lead to more
      structurally diverse PBD dimer analogues.

PMID- 11597417
TI  - Dopaminergic 7-aminotetrahydroindolizines: ex-chiral pool synthesis and
      preferential D3 receptor binding.
AB  - Starting from both isomers of enantiopure asparagine, heterocyclic bioisosteres
      of the preferential dopamine D3 receptor agonist (R)-7-OH-DPAT were investigated
      when SAR studies led to the 3-formyl substituted aminoindolizine (S)-1e (FAUC 54)
      displaying a K(i) value of 6.0 nM for the high affinity D3 binding site. In
      contrast, D3 affinity of the enantiomer (R)-1e was 300 fold lower.

PMID- 11597418
TI  - Pyrimidinylimidazole inhibitors of p38: cyclic N-1 imidazole substituents enhance
      p38 kinase inhibition and oral activity.
AB  - Optimization of a series of N-1-cycloalkyl-4-aryl-5-(pyrimidin-4-yl)imidazole
      inhibitors of p38 kinase is reported. Oral administration of inhibitors
      possessing a cyclohexan-4-ol or piperidin-4-yl group at N-1 in combination with
      alkoxy, amino(alkyl), phenoxy and anilino substitution at the 2-position of the
      pyrimidine was found to potently inhibit LPS-induced TNF in mice and rats. The
      selectivity of these new inhibitors for p38 kinase versus eight other protein
      kinases is high and in all cases exceeds that of SB 203580.

PMID- 11597419
TI  - 2-(Anilinomethyl)imidazolines as alpha(1)-adrenoceptor agonists: the
      identification of alpha(1A) subtype selective 2'-carboxylic acid esters and
      amides.
AB  - 2-(Anilinomethyl)imidazolines with 2'-esters or 2'-amides are potent agonists of
      the cloned human alpha(1)-adrenoceptors in vitro. The size and shape of the ortho
      substituent can have significant effects on the potency, efficacy, and subtype
      selectivity of these 2-(anilinomethyl)imidazolines. alpha(1A)-subtype selective
      agonists have been identified.

PMID- 11597420
TI  - Design and synthesis of Pfmrk inhibitors as potential antimalarial agents.
AB  - The synthesis and inhibitory activities of 10 potential inhibitors of Pfmrk, a
      Plasmodium falciparum cyclin-dependent protein kinase, are described. The most
      potent inhibitor is a 3-phenyl-quinolinone compound with an IC(50) value of 18
      microM. It is the first compound reported to inhibit Pfmrk at the micro molar
      range.

PMID- 11597421
TI  - Cryptoregiochemical analysis of an unusual bacterial desaturation.
AB  - The cryptoregiochemistry of the cold-induced Delta(5) desaturation of long chain
      fatty acids, as it occurs in Bacillus subtilis ATCC 23857, has been examined by
      measuring the individual primary deuterium kinetic isotope effects associated
      with the C-H bond cleavage at C-5 and C-6. The results point to C-5 as the site
      of initial oxidation in Delta(5) desaturation.

PMID- 11597422
TI  - Derivatives of 17-(2-methylallyl)-substituted noroxymorphone: variation of the
      delta address and its effects on affinity and selectivity for the delta opioid
      receptor.
AB  - In an effort to establish the importance of the N-(2-methylallyl) substituent in
      the noroxymorphone series, several derivatives have been synthesized, retaining
      that N-substituent and modifying the delta address moiety. A few compounds showed
      moderate binding affinity and selectivity for the delta receptor; none displayed
      a pharmacological profile as exceptional as N-(2-methylallyl)noroxymorphindole. A
      second study showed that 3-O-methylation of all derivatives decreases binding
      affinity. The present results indicate that only a combination of the N-(2
      methylallyl) group and an indole delta address provided high selectivity for the
      delta receptor.

PMID- 11597423
TI  - A new approach for modification of phenylalanine peptides by Suzuki-Miyaura
      coupling reaction.
AB  - For the first time, we have modified phenylalanine peptides by the Suzuki-Miyaura
      coupling reaction which may be useful in developing combinatorial libraries of
      peptidomimetics.

PMID- 11597426
TI  - Trends in Japanese microbiology.

PMID- 11597427
TI  - Piecing together a puzzling pathway: new insights into C-signaling.

PMID- 11597428
TI  - Is KSHV lytic growth induced by a methylation-sensitive switch?

PMID- 11597430
TI  - Back in the limelight.

PMID- 11597440
TI  - Hepatitis G virus slows HIV.

PMID- 11597442
TI  - Borrelia burgdorferi: a (somewhat) clonal bacterial species.

PMID- 11597444
TI  - Mycobacterium smegmatis: an absurd model for tuberculosis?

PMID- 11597446
TI  - Worms and tuberculosis vaccines.

PMID- 11597447
TI  - Using SHIVs to develop an anti-HIV-1 live-attenuated vaccine.
AB  - The use of chimeric simian and human immunodeficiency viruses (SHIVs) that encode
      HIV-1 Env and are infectious to macaques has made it possible to analyze the
      pathogenicity of HIV-1 in vivo, and to evaluate the efficacy of candidate
      vaccines in macaques. In addition, we believe that gene-deleted SHIVs could
      potentially be used as anti-HIV-1 live-attenuated vaccines. Gene-deleted SHIVs
      replicate transiently, are non-pathogenic and induce strong protection against
      challenge infection. The most important advantage of gene-deleted SHIVs is that
      their efficacy and safety can be evaluated in macaques before they are used in
      humans.

PMID- 11597449
TI  - Diversification of Escherichia coli genomes: are bacteriophages the major
      contributors?
AB  - Determination of the genome sequence of enterohemorrhagic Escherichia coli O157
      Sakai and genomic comparison with the laboratory strain K-12 has revealed that
      the two strains share a highly conserved 4.1-Mb sequence and that each also
      contains a large amount of strain-specific sequence. The analysis also revealed
      the presence of a surprisingly large number of prophages in O157, most of which
      are lambda-like phages that resemble each other. Based on these results, we
      discuss how the E. coli strains have diverged from a common ancestral strain, and
      how bacteriophages contributed to this process. We also describe possible
      mechanisms by which O157 acquired many closely related phages, and raise the
      possibility that such bacteria might function as 'phage factories', releasing a
      variety of chimeric or mosaic phages into the environment.

PMID- 11597450
TI  - The emergence and evolution of methicillin-resistant Staphylococcus aureus.
AB  - Significant advances have been made in recent years in our understanding of how
      methicillin resistance is acquired by Staphylococcus aureus. Integration of a
      staphylococcal cassette chromosome mec (SCCmec) element into the chromosome
      converts drug-sensitive S. aureus into the notorious hospital pathogen methicilin
      resistant S. aureus (MRSA), which is resistant to practically all beta-lactam
      antibiotics. SCCmec is a novel class of mobile genetic element that is composed
      of the mec gene complex encoding methicillin resistance and the ccr gene complex
      that encodes recombinases responsible for its mobility. These elements also carry
      various resistance genes for non-beta-lactam antibiotics. After acquiring an
      SCCmec element, MRSA undergoes several mutational events and evolves into the
      most difficult-to-treat pathogen in hospitals, against which all extant
      antibiotics including vancomycin are ineffective. Recent epidemiological data
      imply that MRSA has embarked on another evolutionary path as a community
      pathogen, as at least one novel SCCmec element seems to have been successful in
      converting S. aureus strains from the normal human flora into MRSA.

PMID- 11597451
TI  - The Sec protein-translocation pathway.
AB  - The Sec machinery (or translocase) provides a major pathway of protein
      translocation from the cytosol across the cytoplasmic membrane in bacteria. The
      SecA ATPase interacts dynamically with the SecYEG integral membrane components to
      drive the transmembrane movement of newly synthesized preproteins. This pathway
      is also used for integration of some membrane proteins and the Sec translocase
      interacts with other cellular components to achieve its cellular roles. The
      detailed protein interactions involved in these processes are being actively
      studied and a structural understanding of the protein-conducting channel has
      started to emerge.

PMID- 11597452
TI  - Recent insights into poliovirus pathogenesis.
AB  - The development of a mouse model for poliomyelitis that is transgenic for the
      human poliovirus receptor (hPVR) has made it much easier to investigate the
      efficiency of the viral dissemination process in a whole organism. These studies
      have given an insight into the mechanisms of blood-brain barrier permeation and
      neural transport. Strain-specific neurovirulence levels, however, appear to
      depend mainly on the replicating capacity of the virus in the central nervous
      system rather than the dissemination efficiency. Studies of the poliovirus
      induced cytopathic effects on neural cells and specific subcellular localization
      of hPVR isoforms might determine a new course of investigation of poliovirus
      pathogenesis.

PMID- 11597453
TI  - The pathogenesis of Ebola hemorrhagic fever.
AB  - Ebola virus causes lethal hemorrhagic disease in humans, yet there are still no
      satisfactory biological explanations to account for its extreme virulence. This
      review focuses on recent findings relevant to understanding the pathogenesis of
      Ebola virus infection and developing vaccines and effective therapy. The
      available data suggest that the envelope glycoprotein and the interaction of some
      viral proteins with the immune system are likely to play important roles in the
      extraordinary pathogenicity of this virus. There are also indications that
      genetically engineered vaccines, including plasmid DNA and viral vectors
      expressing Ebola virus proteins, and passive transfer of neutralizing antibodies
      could be feasible options for the control of Ebola virus-associated disease.

PMID- 11597454
TI  - Institute profile: National Institute of Infectious Diseases.
AB  - A profile of the the National Institute of Infectious Diseases (NIID) at Toyama
      Shinjuku-Ku, Tokyo, Japan.

PMID- 11597455
TI  - QSAR of anticancer compounds. Bis(11-oxo-11H-indeno[1,2-b]quinoline-6
      carboxamides), bis(phenazine-1-carboxamides), and bis(naphthalimides).
AB  - QSAR have been developed for the anticancer activity (growth inhibition) of
      various tumor cells by bis(11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides),
      bis(phenazine-1-carboxamides), and bis(naphthalimides). Of the seven QSAR,
      positive hydrophobic interactions are found in only two examples:
      bis(naphthalimides) versus human colon cancer cells. This is consistent with
      other QSAR of anticancer compounds where hydrophobic interactions are found to be
      unimportant.

PMID- 11597456
TI  - Modified iridoid glycosides as anti-implantation agents: inhibition of cell
      adhesion as an approach for developing pregnancy interceptive agents.
AB  - Structural modifications in iridoid glycosides and evaluation of their efficacy
      on adhering capability (in vitro) of immature hamster uterine epithelial cells to
      the substratum have been studied. Out of 31, eight compounds in vitro, five
      compounds in utero and two in vivo showed adhesion/implantation preventing
      activity, respectively. The results provide an indication for further exploration
      in the line of development of anti-adhesive agents.

PMID- 11597457
TI  - Synthesis of novel GABA uptake inhibitors. Part 6: preparation and evaluation of
      N-Omega asymmetrically substituted nipecotic acid derivatives.
AB  - In a previous series of potent GABA uptake inhibitors published from this
      laboratory, we noticed that asymmetry in the substitution pattern of the bis
      aromatic moiety in known GABA uptake inhibitors such as 4 [1-(4,4-diphenyl-3
      butenyl)-3-piperidinecarboxylic acid] and 5 [(R)-1-(4,4-bis(3-methyl-2-thienyl)-3
      butenyl)-3-piperidinecarboxylic acid] was beneficial for high affinity. This led
      us to investigate asymmetric analogues of known symmetric GABA uptake inhibitors
      in which one of the aryl groups has been exchanged with an alkyl, alkylene or
      cycloalkylene moiety as well as other modifications in the lipophilic part. The
      in vitro values for inhibition of [(3)H]-GABA uptake in rat synaptosomes was
      determined for each compound, and it was found that several of the novel
      compounds inhibit GABA uptake as potently as their known symmetrical reference
      analogues. Several of the novel compounds were also evaluated for their ability
      to inhibit clonic seizures induced by a 15 mg/kg (ip) dose of methyl 6,7
      dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) in vivo. Some of the
      compounds, for example 18 [(R)-1-(2-(((1,2-bis(2
      fluorophenyl)ethylidene)amino)oxy)ethyl)-3-piperidinecarboxylic acid], show a
      high in vivo potency and protective index comparable with that of our recently
      launched anticonvulsant product, 5 [(R)-1-(4,4-bis(3-methyl-2-thienyl)-3-butenyl)
      3-piperidinecarboxylic acid], and may therefore serve as second-generation drug
      candidates.

PMID- 11597458
TI  - QSAR studies on acylated histamine derivatives.
AB  - H(3)-receptor antagonists activity in terms of -log K(i) for a series of acylated
      histamine derivatives was modeled using topological indices, namely negentropy
      (N), molecular redundancy (MRI), and valence connectivity index ((m)x(v))
      indices. Excellent results were obtained in multiple regression analysis upon the
      introduction of a dummy parameter (indicator parameter). Consistent increase in
      R(2)(A) value indicated that inspite of observed collinearity the proposed models
      are significant.

PMID- 11597459
TI  - Synthesis, cytotoxic activity, NMR study and stereochemical effects of some new
      pyrano[3,2-b]thioxanthen-6-ones and pyrano[2,3-c]thioxanthen-7-ones.
AB  - Some new substituted pyrano[3,2-b]thioxanthen-6-ones and pyrano[2,3-c]thioxanthen
      7-ones were prepared and their cytotoxic activity was evaluated using acronycine
      as the reference compound. The conformation of the molecules was also
      investigated in an effort to correlate this parameter with the biological
      activity.

PMID- 11597460
TI  - Immunostimulatory activity of CpG oligonucleotides containing non-ionic
      methylphosphonate linkages.
AB  - Bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CpG
      motifs in a particular sequence context activate vertebrate immune cells. We
      examined the significance of negatively charged internucleoside linkages in the
      flanking sequences 5' and 3' to the CpG-motif on immunostimulatory activity. Cell
      proliferation and secretion of IL-12 and IL-6 in mouse spleen cell cultures, and
      spleen weights of mice increased significantly when a non-ionic linkage was
      placed at least four or more internucleoside linkages away from the CpG-motif in
      the 5'-flanking sequence. When the non-ionic linkage was placed closer than three
      internucleoside linkages in the 5'-flanking sequence to the CpG-motif,
      immunostimulatory activity was suppressed compared with that observed with the
      unmodified parent oligo. In general, the placement of non-ionic linkage in the 3'
      flanking sequence to the CpG-motif either did not affect or slightly increased
      immunostimulatory activity compared with the parent oligo. These results have
      significance in understanding CpG oligonucleotide-receptor interactions and the
      development of potent immunomodulatory agents.

PMID- 11597461
TI  - Synthesis, DNA cleavage, and cytotoxicity of a series of bis(propargylic) sulfone
      crown ethers.
AB  - Compounds that couple molecular recognition of specific alkali metal ions with
      DNA damage may display selective cleavage of DNA under conditions of elevated
      alkali metal ion levels reported to exist in certain cancer cells. We have
      prepared a homologous series of compounds in which a DNA reactive moiety, a
      bis(propargylic) sulfone, is incorporated into an alkali metal ion binding crown
      ether ring. Using the alkali metal ion pricrate extraction assay, the ability of
      these crown ethers to bind Li(+), Na(+), and K(+) ions was determined. For the
      series of crown ethers, the association constants for Li(+) ions are generally
      low (< 2 x 10(4)M(-1)). Only two of the bis(propargylic) sulfone crown ethers
      associate with Na(+) or K(+) ions (K(a) 4-8 x 10(4)M(-1)), with little
      discrimination between Na(+) or K(+) ions. The ability of these compounds to
      cleave supercoiled DNA at pH 7.4 in the presence of Li(+), Na(+), and K(+) ions
      was determined. The two crown ethers that bind Na(+) and K(+) display a modest
      increase in DNA cleavage efficiency in the presence of Na(+) or K(+) ions as
      compared to Li(+) ions. These two bis(propargylic) sulfone crown ethers are also
      more cytotoxic against a panel of human cancer cell lines when compared to a non
      crown ether macrocyclic bis(propargylic) sulfone.

PMID- 11597462
TI  - Testosterone delivery using glutamide-based complex high axial ratio
      microstructures.
AB  - Complex high axial ratio microstructures (CHARMs) were evaluated for delivery of
      testosterone in vivo. Methods to incorporate testosterone included noncovalent
      mixing and covalent attachment of testosterone to the lipid to form a prodrug
      monomer. When prepared by covalent attachment, testosterone-loaded CHARMs were
      resistant to in vitro spontaneous hydrolysis; when injected into rats,
      testosterone was released with biphasic kinetics consisting of a burst followed
      by a much slower phase. Some CHARM material associated with testosterone
      persisted at the site of injection for at least 9 days.

PMID- 11597463
TI  - Synthesis and anti-HIV activity of cosalane analogues incorporating two
      dichlorodisalicylmethane pharmacophore fragments.
AB  - A new series of cosalane analogues incorporating two fragments of the
      dichlorodisalicylmethane pharmacophore has been synthesized. In order to identify
      the position for the attachment of the pharmacophore fragments to the steroid
      ring that results in the most potent analogues, two types of compounds were
      designed. In the first type, the two pharmacophore fragments were attached at C-3
      and C-17 of the steroid ring by using appropriate linker units. In the second
      type, both pharmacophore groups were connected to C-3 of the steroid through an
      alkenyl chain containing an amide moiety. All of the new compounds displayed
      antiviral activity versus HIV-1(RF), HIV-1(IIIB), and HIV-2(ROD) in cell culture.
      The relative potencies of the compounds resulting from the two attachment
      strategies were found to depend on the viral strain as well as the cell type.
      Overall, the attachment of the second pharmacophore did not result in either a
      large gain or a large loss in anti-HIV activity, and the results are therefore
      consistent with the hypothesis that the two pharmacophores act independently, and
      one at a time, with positively charged amino acid side chains present on the
      surface of gp120 and CD4.

PMID- 11597464
TI  - A new acivicin prodrug designed for tumor-targeted delivery.
AB  - Acivicin is an antitumor agent known to inhibit cell growth. A new prodrug 9b of
      acivicin 10 was synthesized, based on a p-hydroxybenzylcarbamate self-immolative
      spacer capable to release acivicin under esterase activity. The prodrug includes
      a maleimide-containing arm for linkage with thiol-containing macromolecules such
      as antibodies. This molecule is intended for the conception of bioconjugates to
      target an inactive acivicin precursor to tumor cells, when linked to a monoclonal
      antibody (mAb) which recognizes a tumor-specific antigen. Prodrug cleavage by
      plasmatic esterases will then restore the acivicin's activity toward tumor cells.
      We report here the synthesis and the in vitro characteristics of the prodrug. As
      expected, its inhibitory activity against the gamma-glutamyl transpeptidase
      (gamma-GT) enzyme and its cytotoxicity towards HL-60 cells were highly reduced
      compared to the parent drug. The chemical and plasmatic hydrolysis kinetics of
      the compound was studied by HPLC. The prodrug is stable, being slowly hydrolyzed
      in pH 7.6 buffer at 37 degrees C with a half-life of 37 h. It is converted into
      an active acivicin under the effect of pig liver esterase, and its half-life in
      human plasma is 3 h. These results indicate this compound may be further used as
      a prodrug-antibody conjugate, to target acivicin to malignant cells.

PMID- 11597465
TI  - Copper(II) complexes with N,N'-dialkyl-1,10-phenanthroline-2,9-dimethanamine:
      synthesis, characterization, DNA-binding thermodynamical and kinetic studies.
AB  - Copper(II) complexes (Cu-L, L=N,N'-dialkyl-1,10-phenanthroline-2,9-dimethanamine)
      were synthesized and characterized by elemental analyses, IR spectra and
      conductance measurement. The interaction of the copper(II) complex with calf
      thymus DNA was studied by means of UV melting experiments, fluorescence spectra
      and circular dichroic spectra. Using ethidium bromide as a fluorescence probe,
      the binding mode of the complexes Cu-L with calf-thymus DNA was studied
      spectroscopically. The results indicate that the complexes Cu-L perhaps interact
      with calf-thymus DNA by both intercalative and covalent binding. Kinetics of
      binding of the cupric complexes to DNA was studied for the first time using
      ethidium bromide as a fluorescence probe with stopped-flow spectrophotometer
      under pseudo-first-order condition. The stronger binding of two steps in the
      process of the complexes Cu-L interacting with DNA was observed, and the probable
      interaction process was discussed in detail. The corresponding k(obs) and E(a) of
      binding to DNA (where k(obs) is the observed pseudo-first-order rate constant,
      E(a) is the observed energy of activation) were obtained.

PMID- 11597466
TI  - An enantioselective synthesis of insecticidal 4-alkynyloxazolines.
AB  - 2-(2,6-Difluorophenyl)-4-phenylalkynyl oxazolines are potent insect growth
      regulators. An efficient and enantioselective synthesis to these compounds has
      been developed which relies on a (-)-sparteine mediated hydroxymethylation of the
      lithium dianion of propargylic amides.

PMID- 11597467
TI  - A pyridone analogue of traditional cannabinoids. A new class of selective ligands
      for the CB(2) receptor.
AB  - A pyridone analogue (5) of the potent bicyclic cannabinoid CP 47,497 (6) has been
      synthesized as a model for one conformational isomer of anandamide and to test
      the hypothesis that an amide carbonyl may serve as a hydrogen bond acceptor in
      interactions with the CB(1) cannabinoid receptor. Pyridone 5 was synthesized from
      6-bromo-2-methoxypyridine (10) by palladium catalyzed coupling with 1-pentyne to
      provide 11. Catalytic hydrogenation of 11 and hydrolysis to pyridone 13 followed
      by N-alkylation gave 1-propyl-6-pentyl-2-pyridone (15). Bromination of 15 gave
      dibromide 18, which underwent Heck coupling with cyclohex-2-en-1-one to give
      enone 19. Catalytic hydrogenation of 19 gave ketone 20 which was reduced using
      NaBH(4) to alcohol 5. Reduction of 20 with K-Selectride gave the axial epimer of
      5 (21). Neither alcohol 5 nor 21 have significant affinity for the CB(1) receptor
      (K(i) > 970 nM), but both have moderately high affinity for the CB(2) receptor
      (K(i) < 60 nM).

PMID- 11597469
TI  - Comparative QSAR studies on bibenzimidazoles and terbenzimidazoles inhibiting
      topoisomerase I.
AB  - Terbenzimidazoles that inhibit topoisomerase are of interest as anticancer drugs.
      We have reviewed the literature and have developed 13 quantitative structure
      activity relationships (QSARs) on cleaving DNA or inhibiting the growth of tumor
      cell cultures. The results are correlated with octanol/water partition
      coefficients or molecular refractivity. Suggestions have been made for the
      development of improved derivatives.

PMID- 11597468
TI  - Simple isoquinoline and benzylisoquinoline alkaloids as potential antimicrobial,
      antimalarial, cytotoxic, and anti-HIV agents.
AB  - Twenty-six simple isoquinolines and 21 benzylisoquinolines were tested for
      antimicrobial, antimalarial, cytotoxic, and anti-HIV activities. Some simple
      isoquinoline alkaloids were significantly active in each assay, and may be useful
      as lead compounds for developing potential chemotherapeutic agents. These
      compounds include 13 (antimicrobial), 25, 26, and 42 (antimalarial), 13 and 25
      (cytotoxic), and 28 and 29 (anti-HIV). A quaternary nitrogen atom of isoquinolium
      or dihydroisoquinolinium type may contribute to enhanced potency in the first
      three types of activities. In contrast, anti-HIV activity was found with
      tetrahydroisoquinoline and 6,7-dihydroxyisoquinolium salts.

PMID- 11597470
TI  - Oligonucleotides containing a lysine residue as 3'-3' junction for alternate
      strand triple helix formation.
AB  - Oligonucleotides with a 3'-3' inversion of polarity site assured by one lysine
      residue have been synthesized, characterized and used as third strands in
      alternate strand triple helix formation. UV melting studies and molecular
      mechanics calculations have been carried out to investigate the stability and the
      geometry of these new triplexes.

PMID- 11597471
TI  - Synthesis and biochemical investigation of scyphostatin analogues as inhibitors
      of neutral sphingomyelinase.
AB  - The sphingolipid ceramide is considered to be an important intracellular
      mediator. However, many aspects of its action and the role of several different
      ceramide generating sphingomyelinases are still unclear. Recently, we reported on
      the synthesis of the first selective irreversible inhibitor of the neutral
      sphingomyelinase (N-SMase), as well as the identification of Manumycin A and some
      of its analogues as irreversible inhibitors of N-SMase. For the development of
      pharmacologically interesting competitive inhibitors of N-SMase, structure
      activity studies are essential. Herein we show the synthesis and enzymatic
      investigation of two scyphostatin analogues 3a and 3b, revealing the importance
      of the primary hydroxy group in compound 2 for N-SMase inhibition.

PMID- 11597472
TI  - Tris-benzimidazole derivatives: design, synthesis and DNA sequence recognition.
AB  - Two tris-benzimidazole derivatives have been designed and synthesized based on
      the known structures of the bis-benzimidazole stain Hoechst 33258 complexed to
      short oligonucleotide duplexes derived from single crystal X-ray studies and from
      NMR. In both derivatives the phenol group has been replaced by a methoxy-phenyl
      substituent. Whereas one tris-benzimidazole carries a N-methyl-piperazine at the
      6-position, the other one has this group replaced by a 2-amino-pyrrolidine ring.
      This latter substituent results in stronger DNA binding. The optimized synthesis
      of the drugs is described. The two tris-benzimidazoles exhibit high AT-base pair
      (bp) selectivity evident in footprinting experiments which show that five to six
      base pairs are protected by the tris-benzimidazoles as compared to four to five
      protected by the bis-benzimidazoles. The tris-benzimidazoles bind well to
      sequences like 5'-TAAAC, 5'-TTTAC and 5'-TTTAT, but it is also evident that they
      can bind weakly to sequences such as 5'-TATGTT-3' where the continuity of an AT
      stretch is interrupted by a single G*C base pair.

PMID- 11597473
TI  - Velnacrine thiaanalogues as potential agents for treating Alzheimer's disease.
AB  - The only therapeutic drugs for combating dementia disease are acetylcholine
      esterase inhibitors (AChEI). However, the use of tacrine, the first AChEI to be
      launched as an Alzheimer's disease (AD) drug, has been limited by serious side
      effects. Therefore, efforts to search for more potent and selective inhibitors of
      AChE still remain highly significant in the therapeutic treatment of AD. In this
      work we modified the cyclohexyl ring of velnacrine, a less toxic analogue of
      tacrine, by synthesizing a series of thiopyranoquinolines in which the C-3
      methylene unit was replaced by a sulphur atom. The anti-AChE data show that the
      activity was maintained with the bioisosteric substitution carried out. The
      introduction of a chlorine atom at different positions of the aromatic ring
      resulted in an array of different activities. In an attempt to understand the
      different behaviours displayed by the chlorine-substituted derivatives, a
      molecular docking study was performed.

PMID- 11597474
TI  - Synthesis of 2,4-diamino-6-(thioarylmethyl)pyrido[2,3-d]pyrimidines as
      dihydrofolate reductase inhibitors.
AB  - Six 2,4-diaminopyrido[2,3-d]pyrimidines with a 6-methylthio bridge to an aryl
      group were synthesized and biologically evaluated as inhibitors of Pneumocystis
      carinii (pc) and Toxoplasma gondii (tg) dihydrofolate reductase (DHFR). The
      syntheses of analogues 3-8 were achieved by nucleophilic displacement of 2,4
      diamino-6-bromomethylpyrido[2,3-d]pyrimidine 14 with various arylthiols. The
      alpha-naphthyl analogue 4 showed the highest selectivity ratios of 3.6 and 8.7
      against pcDHFR and tgDHFR, respectively, versus rat liver (rl) DHFR. The beta
      naphthyl analogue 5 exhibited the highest potency within the series with an
      IC(50) value against pcDHFR and tgDHFR of 0.17 and 0.09 microM, respectively.
      Analogue 4 was evaluated for in vitro antimycobacterium activity and was shown to
      inhibit the growth of Mycobacterium tuberculosis H(37)Rv cells by 58% at a
      concentration of 6.25 microg/mL.

PMID- 11597475
TI  - Formation of 2-chloroinosine from guanosine by treatment of HNO(2) in the
      presence of NaCl.
AB  - We investigated the reaction of Guo with nitrous acid in the presence of NaCl.
      When 1 mM Guo was incubated with 100 mM NaNO(2) and 2M NaCl in sodium acetate
      buffer at pH 3.2 and 37 degrees C, 2-chloroinosine (2-Cl-Ino) was produced in
      addition to oxanosine (Oxo) and xanthosine (Xao). The yield of 2-Cl-Ino was 0.033
      mM at an incubation time of 2 h. Under the same reaction conditions, GMP and dGuo
      gave rise to the corresponding 2-chloro derivatives with comparable yields. All
      the 2-chloro derivatives were fairly stable (t(12)>360 h) at physiological pH and
      temperature. To elucidate the reaction mechanism of the chlorination, the
      diazoate derivative of Guo, a reaction intermediate of the Guo-HNO(2) system, was
      employed as a starting compound. When the diazoate was incubated with 2M NaCl in
      a neutral solution, 2-Cl-Ino was produced in addition to Oxo and Xao. These
      results suggest that the 2-chloro derivatives can be produced from foodstuffs in
      the human stomach and may have potential importance as a carcinogen causing
      gastric cancer.

PMID- 11597476
TI  - Immobilisation on polystyrene of diazirine derivatives of mono- and
      disaccharides: biological activities of modified surfaces.
AB  - The potential of surface glycoengineering for biomaterials and biosensors
      originates from the importance of carbohydrate-protein interactions in biological
      systems. The strategy employed here utilises carbene generated by illumination of
      diazirine to achieve covalent bonding of carbohydrates. Here, we describe the
      synthesis of an aryl diazirine containing a disaccharide (lactose). Surface
      analysis techniques [X-ray photoelectron spectroscopy (XPS) and time of flight
      secondary ion mass spectroscopy (ToF-SIMS)] demonstrate its successful surface
      immobilisation on polystyrene (PS). Results are compared to those previously
      obtained with an aryl diazirine containing a monosaccharide (galactose). The
      biological activity of galactose- or lactose-modified PS samples is studied using
      rat hepatocytes, Allo A lectin and solid-phase semi-synthesis with alpha-2,6
      sialyltransferase. Allo A shows some binding to galactose-modified PS but none to
      lactose-modified surfaces. Similar results are obtained with rat hepatocytes. In
      contrast, sialylation of lactose-modified PS is achieved but not with galactose
      modified surfaces. The different responses indicate that the biological activity
      depends not only on the carbohydrate per se but also on the structure and length
      of the spacer.

PMID- 11597477
TI  - Ethenesulfonamide and ethanesulfonamide derivatives, a novel class of orally
      active endothelin-A receptor antagonists.
AB  - In the previous paper, we described a series of 2-phenylethenesulfonamide
      derivatives, a novel class of ET(A)-selective endothelin (ET) receptor
      antagonists, including the 2-methoxyethoxy derivative 2a and the 2-fluoroethoxy
      derivative (2b). In this paper, we wish to report further details of structure
      activity relationships (SARs) of the two regions of the molecule in compound 2b,
      which were the alkoxy region at the 6-position of the core pyrimidine ring and
      the 2-phenylethenesulfonamide region. In these modifications, replacement of the
      2-fluoroethoxy group with a methoxy group (6e) and replacement of the 2
      phenylethenesulfonamide group with a 2-(pyridin-3-yl)ethenesulfonamide group (6l)
      or 2-phenylethanesulfonamide group (6q) were well tolerated both in the ET(A)
      binding affinity and ET(A) selectivity. Among them, compound 6e showed further
      improvement in oral activity compared to 2b. After oral administration, compound
      6e inhibited the big ET-1 induced pressor response in conscious rats at 0.3mg /kg
      with a duration of >6.5h. Compound 6e also exhibited a potent antagonistic
      activity in the pithed rats.

PMID- 11597478
TI  - Synthesis of galactosyl compounds for targeted gene delivery.
AB  - Cell-specific DNA delivery offers a great potential for targeted gene therapy.
      Toward this end, we have synthesized a series of compounds carrying galactose
      residues as a targeting ligand for asialoglycoprotein receptors of hepatocytes
      and primary amine groups as a functional domain for DNA binding. Biological
      activity of these galactosyl compounds in DNA delivery was evaluated in HepG2 and
      BL-6 cells and compared with respect to the number of galactose residues as well
      as primary amine groups in each molecule. Transfection experiments using a
      firefly luciferase gene as a reporter revealed that compounds with multivalent
      binding properties were more active in DNA delivery. An optimal transfection
      activity in HepG2 cells requires seven primary amine groups and a minimum of two
      galactose residues in each molecule. The transfection activity of compounds
      carrying multi-galactose residues can be inhibited by asialofetuin, a natural
      substrate for asialoglycoprotein receptors of hepatocytes, suggesting that gene
      transfer by these galactosyl compounds is asialoglycoprotein receptor-mediated.
      These results provide direct evidence in support of our new strategy for the use
      of small and synthetic compounds for cell specific and targeted gene delivery.

PMID- 11597479
TI  - Synthesis of pyridino[2,3-f]indole-4,9-dione and 6,7-disubstituted quinoline-5,8
      dione derivatives and evaluation on their cytotoxic activity.
AB  - We report upon the synthesis of the following derivatives: N-substituted
      pyridino[2,3-f]indole-4,9-dione, and 6-(alpha-diethoxycarbonyl-methyl)-7
      substituted-amino-quinoline-5,8-dione, which contain the active quinoline-5,8
      dione (VII) moiety. The cytotoxic activities of these compounds have been tested
      in SRB (SulfoRhodamine B) assays against the cancer cell lines of A-549 (human
      lung cancer), SK-MEL-2 (human melanoma cancer), SK-OV-3 (human ovarian cancer),
      XF-498 (human brain cancer) and HCT 15 (human colon cancer). The compound, N
      benzyl-3-ethoxycarbonyl-2-hydroxy-pyridino[2,3-f]indole-4,9-dione (A-9), also
      showed higher activity than cis-platin. The highest level of cytotoxic activity
      in these human tumor cell lines was observed in the compound 6-(alpha
      diethoxycarbonyl-methyl)-7-(2-methyl-phenylamino)-quinoline-5,8-dione (B-3).

PMID- 11597480
TI  - The 3-D QSAR study of anticancer 1-N-substituted imidazo- and pyrrolo-quinoline
      4,9-dione derivatives by CoMFA and CoMSIA.
AB  - The 3-D QSAR analysis with new imidazo- and pyrrolo-quinolinedione derivatives
      was conducted by Comparative Molecular Field Analysis (CoMFA) and Comparative
      Molecular Similarity Indices Analysis (CoMSIA). When crossvalidation value (q(2))
      is 0.844 at four components, the Pearson correlation coefficient (r(2)) of the
      CoMFA is 0.964. In the CoMSIA, q(2) is 0.709 at six components and r(2) is 0.969.
      Unknown samples were analyzed, using QSAR analyzed results from the CoMFA and
      CoMSIA methods. Excellent agreement was obtained between, with an error range of
      0.01-0.15 the calculated values and measured in vitro cytotoxic activities
      against human lung A-549 cancer cell lines.

PMID- 11597481
TI  - Synthesis, characterization and reactions of 2-deoxo-5-deazaalloxazines.
AB  - 5-Deazaflavins and their homologues have been known as potential riboflavin
      antagonists, bioreductives, and compounds with potent antitumor activity. 2-Amino
      4-methylquinoline-3-carbonitrile (2) was prepared as unreported starting material
      for several interesting 2-deoxo-5-deazalloxazine derivatives. Cyclization of 2
      using formamide afforded the 2,4-deoxo-5-deazaalloxazine derivative 7, which was
      subjected to deamination with nitrous acid to give the 2-deoxo-5-deazaalloxazine
      (8). The compound 8 was also obtained via 13 by treating the latter with
      refluxing formic acid or formamide and used as a precursor for synthesis of
      several 2-deoxo-5-deazaalloxazines 18, 19, 20, 21 and 22. The pharmacological and
      biological properties of these compounds are still under investigation.

PMID- 11597482
TI  - Antitumor agents 210. Synthesis and evaluation of taxoid-epipodophyllotoxin
      conjugates as novel cytotoxic agents.
AB  - Five compounds composed of a taxoid (paclitaxel or cephalomannine) and a 4'-O
      demethyl epipodophyllotoxin derivative joined by an imine linkage were prepared
      and evaluated as cytotoxic agents and inhibitors of mammalian DNA topoisomerase
      II. Compounds 12 and 14-16 exhibited comparable or better activity than the
      unconjugated epipodophyllotoxin derivatives in most tumor cell lines, and 12, 15,
      and 16 also showed enhanced activity against paclitaxel-resistant cells. Compound
      13, which contains an epipodophyllotoxin moiety at both the taxoid 2' and 7
      positions, did not stimulate protein-DNA breaks, but was 2-fold more potent than
      12 and 15 and comparable to GL-331 in the topo II inhibitory assay.

PMID- 11597483
TI  - Simultaneous binding of mouse monoclonal antibody and streptavidin to
      heterobifunctional dendritic L-lysine core bearing T-antigen tumor marker and
      biotin.
AB  - Thiolated T-antigen [Galbeta-(1-3)-GalNAcalpha, T-Ag] (6), derived in situ from
      thioacetate 5 was coupled to N-chloroacetylated glycylglycyl L-lysine dendritic
      cores (7-9) using high yielding substitution reactions to afford di- (10), tetra-
      (11), and octa-valent (12) glycodendrimers in good yields (76-86%).
      Heterobifunctional conjugate 14 was prepared as a biosensor from tetravalent
      conjugate 11 and biotin hydrazide 13 using TBTU strategy. In a solid-phase double
      sandwich enzyme linked immunosorbent assays (ELISA), biotinylated conjugate 14
      was shown to bind to streptavidin used as a coating material. Mouse monoclonal
      anti T-Ag antibody (IgG3) and horseradish peroxydase-labeled goat anti mouse IgG,
      used for quantification, were found to bind T-Ag tetramer 14 immobilized on the
      surface of the streptavin layer. A typical saturation curve was observed for 14
      while non-biotinylated tetramer 11 showed no binding in the entire concentration
      range. These results demonstrate the availability of both haptens toward the T-Ag
      antibody and streptavidin receptors.

PMID- 11597484
TI  - Synthesis and phosphodiesterase inhibitory activity of new sildenafil analogues
      containing a carboxylic acid group in the 5'-sulfonamide moiety of a phenyl ring.
AB  - New sildenafil analogues possessing a carboxylic acid group in the 5'-sulfonamide
      of the phenyl ring, 9a-l, were prepared from the readily available starting
      compounds 6a-b and cyclic amines 3-5 in a three-step sequence. In the enzyme
      assays, it has been shown that all the target compounds 9a-l proved to be more
      potent in inhibiting phosphodiesterase type 5 (PDE5) than sildenafil by 4-38
      fold. The effects on the IC(50) values were investigated by varying the alkoxy
      group (R) of the phenyl ring, the sulfonamide type (X), and the length of the
      methylene chain linking the carboxylic acid, and the results were discussed in
      detail. From this study, we have clearly demonstrated that introduction of a
      carboxylic acid group to the 5'-sulfonamide moiety of the phenyl ring greatly
      enhanced PDE5 inhibitory activity, probably by mimicking the phosphate group of
      cGMP. The piperidinyl propionic acid derivative 9i, which showed the highest PDE5
      inhibitory activity and comparable to better selectivity over PDE isozymes in
      comparison with sildenafil, has been selected for more detailed biological
      investigations.

PMID- 11597485
TI  - Modification of cell response to insulin by membrane-acting agents in rat white
      adipocytes: analysis of structural features by computational simulation.
AB  - The effect of membrane-acting agents, biscoclaurine alkaloids (cepharanthine,
      tetrandrine, isotetrandrine), carbobenzoxy-D-Phe-L-Phe-Gly (z-FFG), and
      tyrphostin AG17, on the insulin-involved fatty acid synthesis by an beta-agonist
      (e.g., isoproterenol) in adipocytes was examined. The alkaloids dose-dependently
      enhanced the insulin-involved fatty acid synthesis in rat white adipocytes,
      stabilized the C(6)-NBD-PC (1-acyl-2-[6-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]
      caproyl]-sn-glycero-3-phosphatidylcholine) model membrane, and suppressed the
      phospholipase A(2)-induced phospholipid degradation. In contrast, z-FFG had no
      effect on the fatty acid synthesis or the membrane stability. Tyrphostin AG17
      suppressed insulin action, but promoted the model membrane stabilization. In the
      same culture conditions as for the fatty acid synthesis assay, cepharanthine, z
      FFG and tyrphostin AG17 had no effect on the transcript levels of glucose
      transporter isoforms (GLUT 1, 4) and hexokinase isozymes (HK I, II) in rat white
      adipocytes. Thus, these membrane-acting agents modify the insulin action via a
      change in the cell membrane condition, and do not directly act on the insulin
      involved glucose metabolism. Then we analyzed the structural conformation of
      these membrane-acting agents by computational simulations. The alkaloids had an
      elliptic macrocyclic structure, and the order of ellipticity
      (cepharanthine>tetrandrine>isotetrandrine) agreed with that of the modifying
      ability for insulin action. The distribution of electrostatic potential fields of
      these alkaloids was essentially equal by turn in surrounding with the dipole
      moments. Both in z-FFG and tyrphostin AG17, the distribution pattern of
      electrostatic potential fields was different from that of the alkaloids. Judging
      from these results, we concluded that the electrostatic potential field is a good
      index of the modification of insulin action, and the elliptic structure in these
      alkaloids is regarded with the modification of insulin action.

PMID- 11597486
TI  - QSAR prediction of toxicity of nitrobenzenes.
AB  - A QSAR analysis has been carried out on the toxicities of 40 mono-substituted
      nitrobenzenes using recently introduced PI and Sz indices, as well as older
      molecular redundancy (MRI) and Balaban indices (J). The results have shown that
      no statistically significant mono-parametric QSAR models are possible. Also, that
      along with PI, Sz, MRI and J indices are the appropriate parameters to be used in
      developing multiparametric QSAR models. The toxicities of nitrobenzenes are well
      predicted by a penta-parametric model consisting of PI, Sz, J, MRI and Ip(1) (an
      indicator parameter taking care of the effect of substitution at 2-position) as
      the correlating parameters. The predictive ability of the model is determined by
      a cross-validation method.

PMID- 11597487
TI  - 3-Hydroxy-(4H)-benzopyran-4-ones as potential iron chelating agents in vivo.
AB  - Increasing evidence suggests that iron plays an important role in tissue damage
      both during chronic iron overload diseases (i.e., hemochromatosis) and when, in
      the absence of actual tissue iron overload, iron is delocalised from specific
      carriers or intracellular sites (inflammation, neurodegenerative diseases, post
      ischaemic reperfusion, etc.). In order to be used for therapeutical purposes in
      vivo, a reliable iron chelator should be capable of preventing the undesired
      effects that follow the electrochemical activation of iron (see below). Bearing
      in mind the molecular structure of some flavonols that are able to chelate iron,
      we synthesised a new oral iron-chelator, 2-methyl-3-hydroxy-4H-benzopyran-4-one
      (MCOH). We demonstrate that MCOH chelates iron in a 2:1 ratio showing a stability
      constant of approximately 10(10). MCOH is able to cross cell membranes
      (erythrocytes, ascite tumour cells) in both directions. Following intraperitoneal
      administration to rats, it is quickly taken up by the liver and excreted in the
      urine within 24h. A similar behaviour has been documented after oral
      administration. We propose that MCOH may represent the prototype of a new class
      of iron chelating agents to be developed for iron-removal therapy in vivo with
      the goal of preventing tissue damage caused by the iron redox cycle.

PMID- 11597488
TI  - Coscinosulfate, a CDC25 phosphatase inhibitor from the sponge Coscinoderma
      mathewsi.
AB  - The dual specificity CDC25 phosphatases dephosphorylate two inhibitory phospho
      amino acids of cyclin-dependent kinases, a major family of cell cycle regulators.
      CDC25 inhibitors constitute new anti-mitotic agents with potential anticancer
      activity. While screening through a collection of natural products derived from
      marine organisms for CDC25A inhibitors, we purified and identified coscinosulfate
      1, a sesquiterpene sulfate from the New Caledonian sponge Coscinoderma matthewsi,
      along with 4. The purified compound 1 displayed significant inhibitory activity
      towards CDC25A (IC(50): 3 microM).

PMID- 11597489
TI  - Radiosynthesis of 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-[(11)C]methyl-2-(S)
      pyrrolidinylmethoxy)pyridine, a high affinity ligand for studying nicotinic
      acetylcholine receptors by positron emission tomography.
AB  - 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)pyridine
      (1b) exhibited high affinity for nicotinic acetylcholine receptors in the in
      vitro competition binding assays, with a K(d) value in the low picomolar range,
      performed at room temperature and at physiological temperature. An efficient
      radiochemical synthesis of 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-[(11)C]methyl-2
      (S)-pyrrolidinylmethoxy)pyridine (1c), a potential tracer for the study of nAChR
      by positron emission tomography, has been developed.

PMID- 11597490
TI  - A quantitative structure-activity relationship study on some HIV-1 protease
      inhibitors using molecular connectivity index.
AB  - A quantitative structure-activity relationship (QSAR) study has been made on two
      different series of tetrahydropyrimidinones acting as HIV-1 protease inhibitors.
      A structural parameter, the first order valence molecular connectivity index
      ((1)chi(v)), has been used to account for the variation in the activity. The
      protease inhibition activity as well as the antiviral potency of the compounds
      are found to be significantly correlated with (1)chi(v) of P(2)/P(2')
      substituents attached to the two nitrogens N1 and N3, suggesting that
      substituents containing less electronegative and more saturated atoms, meaning
      thereby the less polar or more hydrophobic substituents, will be more
      advantageous. Further, if P(2) and P(2') are dissimilar, the former is found to
      be more effective than the latter. This difference is attributed to a
      conformational change in the enzyme that may be more favorable to P(2) binding
      than to P(2') binding.

PMID- 11597491
TI  - Design, synthesis and pharmacological evaluation of 3-benzylazetidine-2-one-based
      human chymase inhibitors.
AB  - 3-Benzylazetidine-2-one derivatives were designed and evaluated as a novel series
      of chymase inhibitors. Structure-activity relationship studies of 3
      benzylazetidine-2-ones led to compounds 23, which exhibited 3.1 nM inhibition of
      human chymase and enhancement of stability in human plasma (t(1/2) 6h).

PMID- 11597494
TI  - Auxin signalling: the beginning, the middle and the end.
AB  - The plant hormone auxin is central to the regulation of growth and development.
      Recent work has demonstrated that auxin signalling depends on targeted protein
      degradation, and in the past year this model has been strengthened. The focus is
      now on identifying the targets of this degradative pathway, determining how auxin
      influences the degradative process and linking the turnover of specific proteins
      to the numerous downstream responses to auxin.

PMID- 11597495
TI  - Genetic interactions between ABA, ethylene and sugar signaling pathways.
AB  - The identification of genes through mutant screens is beginning to reveal the
      structure of a number of signaling pathways in plants. In the past year, genes
      that determine the plant's response to the hormones ethylene and abscisic acid
      have also been shown to be involved in sugar sensing in early seedlings. These
      results suggest that hormone signaling and carbon homeostasis are tightly coupled
      but that the architecture of these interactions is complex. Part of this
      complexity may be because some genetic screens on exogenous compounds produce
      signaling linkages that are not necessarily pertinent under normal growth
      conditions. Because many of the genes identified in these screens are cloned, the
      relevance of these interactions can now be unraveled at the molecular level.

PMID- 11597496
TI  - Plant mitogen-activated protein kinase signaling cascades.
AB  - Mitogen-activated protein kinase (MAPK) cascades have emerged as a universal
      signal transduction mechanism that connects diverse receptors/sensors to cellular
      and nuclear responses in eukaryotes. Recent studies in plants indicate that MAPK
      cascades are vital to fundamental physiological functions involved in hormonal
      responses, cell cycle regulation, abiotic stress signaling, and defense
      mechanisms. New findings have revealed the complexity and redundancy of the
      signaling components, the antagonistic nature of distinct pathways, and the use
      of both positive and negative regulatory mechanisms.

PMID- 11597497
TI  - Cell signaling under salt, water and cold stresses.
AB  - Forward genetics and biochemical approaches to studying plant responses to salt,
      water and cold stresses began to bear fruit recently. Analysis of salt overly
      sensitive (sos) Arabidopsis mutants revealed a novel calcium-regulated protein
      kinase pathway for response to the ionic aspect of salt stress. In-gel kinase
      assays identified several SOS-independent protein kinases that are either
      activated specifically by osmotic stress or by multiple abiotic and biotic
      stresses. Molecular analysis revealed a transcriptional cascade in cold-regulated
      gene expression.

PMID- 11597498
TI  - Protein kinases in the plant defence response.
AB  - Protein kinases play a central role in signalling during pathogen recognition and
      the subsequent activation of plant defence mechanisms. Members of different
      kinase subfamilies, such as calcium-dependent protein kinases and MAP kinases,
      are involved. Nevertheless, often, only a single component of a signalling
      cascade in an experimental plant system has been characterised. The future
      challenge is to understand how these kinases work, which cellular responses they
      mediate, and how they fit into the bigger picture of defence signalling. This
      challenge has become increasingly feasible with the recent introduction of new
      techniques: these techniques include reverse genetics, which will allow the
      allocation of biological function to kinase isoforms, (phospho) proteomics
      combined with mass spectrometry, and transient expression of kinases in a
      (constitutively) active form, mimicking the induction of defence responses in a
      biological system.

PMID- 11597499
TI  - Calcium oscillations in higher plants.
AB  - There is considerable interest in the possibility that stimulus-induced
      oscillations in cytosolic free calcium encode information that is used to specify
      the outcome of the final response in calcium-based signalling pathways in plants.
      Recent results provide conclusive evidence that plant cells can decipher complex
      calcium signatures.

PMID- 11597500
TI  - From milliseconds to millions of years: guard cells and environmental responses.
AB  - During the past year, significant advances have been made in our understanding of
      stomatal development and its response to climate change, and in our knowledge of
      how guard cell Ca(2+) oscillations encode environmental signals. Recent studies
      on (de)phosphorylation mechanisms have provided new information on how guard
      cells respond to abscisic acid and blue light.

PMID- 11597501
TI  - Signaling networks in the plant circadian system.
AB  - Significant advances have been made during the past year in the genetic and
      molecular dissection of the plant circadian system. Several proteins involved in
      circadian clock regulation have been identified and the way that their
      interactions contribute to temporal organization is starting to emerge. In
      addition, genomic approaches have identified hundreds of genes under clock
      control, providing a molecular basis to our understanding of how the clock
      coordinates plant physiology and development with daily and seasonal
      environmental cycles.

PMID- 11597502
TI  - Photocontrol of stem growth.
AB  - Rapid and measurable growth rate changes that occur in seedling stems upon
      illumination serve as an excellent means to analyze signal transduction. Growth
      kinetic studies have shown how red, far-red and blue light signals are transduced
      via the solitary and/or coordinated action of known plant photoreceptors. These
      reports are consistent with current findings describing light-induced
      photoreceptor interaction and compartmentation.

PMID- 11597503
TI  - Cell-cell signaling in the shoot meristem.
AB  - The shoot meristem is a proliferating, changing cell population yet displays a
      stable organization. Recent studies have addressed how signaling processes
      coordinate the behaviour of shoot meristem cells.

PMID- 11597504
TI  - The R2R3-MYB gene family in Arabidopsis thaliana.
AB  - MYB factors represent a family of proteins that include the conserved MYB DNA
      binding domain. In contrast to animals, plants contain a MYB-protein subfamily
      that is characterised by the R2R3-type MYB domain. 'Classical' MYB factors, which
      are related to c-Myb, seem to be involved in the control of the cell cycle in
      animals, plants and other higher eukaryotes. Systematic screens for knockout
      mutations in MYB genes, followed by phenotypic analyses and the dissection of
      mutants with interesting phenotypes, have started to unravel the functions of the
      125 R2R3-MYB genes in Arabidopsis thaliana. R2R3-type MYB genes control many
      aspects of plant secondary metabolism, as well as the identity and fate of plant
      cells.

PMID- 11597505
TI  - Chromatin remodelling.
AB  - Epigenetic mechanisms are heritable traits that are mediated by changes in a
      genetic locus that do not involve a modification at the nucleotide level. As
      eukaryotic DNA is organised in chromatin units, epigenetic modifications can be
      mediated by chromatin remodelling. Although there are a number of well
      characterised chromatin remodelling factors to which we can allocate a defined
      molecular function, we need to understand chromatin remodelling processes as the
      combined effects of such factors in higher order complexes.

PMID- 11597506
TI  - NEMO/IKK gamma: linking NF-kappa B to human disease.

PMID- 11597507
TI  - Making sense of antisense.

PMID- 11597508
TI  - Spotting prostate cancer.

PMID- 11597510
TI  - Cilomilast: a breath of relief?

PMID- 11597515
TI  - First rat HIV model.

PMID- 11597517
TI  - Caveolae and caveolin-3 in muscular dystrophy.
AB  - Caveolae are vesicular invaginations of the plasma membrane, and function as
      'message centers' for regulating signal transduction events. Caveolin-3, a muscle
      specific caveolin-related protein, is the principal structural protein of
      caveolar membrane domains in skeletal muscle and in the heart. Several mutations
      within the coding sequence of the human caveolin-3 gene (located at 3p25) have
      been identified. Mutations that lead to a loss of approximately 95% of caveolin-3
      protein expression are responsible for a novel autosomal dominant form of limb
      girdle muscular dystrophy (LGMD-1C) in humans. By contrast, upregulation of the
      caveolin-3 protein is associated with Duchenne muscular dystrophy (DMD). Thus,
      tight regulation of caveolin-3 appears essential for maintaining normal muscle
      health and homeostasis.

PMID- 11597518
TI  - PET as a potential tool for imaging molecular mechanisms of oncology in man.
AB  - During the past ten years, positron emission tomography (PET) has been
      increasingly developed for imaging and quantifying molecular mechanisms in
      oncology. The technique uses radionuclides to label molecules, which can then be
      imaged in man. The inherent sensitivity and specificity of PET is unrivalled
      because it can image molecular interactions and pathways, providing quantitative
      kinetic information down to the subpicomolar level. This technology has the
      potential to answer a large number of important clinical questions in
      translational research in oncology. However, the challenges in the methodology
      are substantial. Molecular imaging has the potential to assist in the
      optimization of molecular-based targeted therapies in cancer and to investigate
      the function of the genome.

PMID- 11597520
TI  - Phosphoinositide 3-kinases in the gut: a link between inflammation and cancer?
AB  - Carcinoma of the gastrointestinal tract is the most common internal malignancy
      affecting men and women in Western countries. Chronic intestinal inflammation,
      especially of the colon, is also a Western disease and correlates with a
      significantly increased risk of developing cancer. This has suggested that the
      immune processes involved in both conditions might share some common pathways.
      Indeed, there is increasing evidence that phosphatidylinositol 3-kinases (PI 3
      kinases) are involved in both the pathogenesis of colorectal carcinoma and
      intestinal inflammation. Here, we discuss this rapidly progressing area of
      research, presenting evidence for a pivotal role of PI 3-kinase(s) in intestinal
      pathophysiology.

PMID- 11597519
TI  - The growth hormone-insulin-like growth factor-I axis and colorectal cancer.
AB  - The growth hormone (GH)-insulin-like growth factor (IGF)-I axis is an important
      modulator of growth and development, but in addition to their classical role as
      endocrine hormones, its components also regulate a wide range of biological
      functions through paracrine and autocrine mechanisms. Their potent mitogenic and
      anti-apoptotic effects play a critical role in the regulation of rapidly renewing
      epithelial cell populations such as those found in the colon. Recent evidence
      suggests an association between inappropriate regulation of the GH-IGF-I axis and
      the development of colorectal cancer. However, the molecular mechanisms and
      signalling pathways responsible are only beginning to be unravelled, as are the
      relative contributions of the endocrine and autocrine or paracrine effects.

PMID- 11597521
TI  - Recombinant vaccines for hepatitis E.
AB  - Hepatitis E virus causes epidemics of acute hepatitis in many developing
      countries. It infrequently causes disease in developed countries, but avirulent
      strains might circulate. Some evidence suggests that hepatitis E might be a
      zoonosis. There is probably only a single serotype. A candidate vaccine
      consisting of baculovirus-expressed recombinant capsid protein protected macaques
      from hepatitis E--it passed phase I clinical trials and is currently scheduled
      for phase II/III clinical trials.

PMID- 11597522
TI  - Analysis of tauopathies with transgenic mice.
AB  - Intraneuronal filamentous inclusions composed of the microtubule-associated
      protein tau are a feature of several neurodegenerative diseases (including
      Alzheimer's disease) known as tauopathies. A pivotal finding was the
      identification in 1998 of mutations in tau associated with frontotemporal
      dementia with parkinsonism linked to chromosome 17. This demonstrated that tau
      dysfunction is sufficient to cause neurodegeneration, and indicated that tau is
      likely to play a crucial role in the pathogenesis of other tauopathies. However,
      the mechanism by which tau filamentous lesions form and their role in
      neurodegeneration remains uncertain. Recent progress in the development of
      transgenic mouse models of human tauopathy is allowing these questions to be
      addressed.

PMID- 11597523
TI  - Spontaneous adenocarcinoma mouse models for immunotherapy.
AB  - Recent discoveries regarding the identification of tumor-associated antigens and
      antigen presentation have made successful immunotherapy strategies possible with
      little, if any, toxicity. Here, we describe transgenic mammary, pancreas,
      prostate, stomach and lung adenocarcinoma animal models that can be used to study
      various immunotherapeutic strategies. The challenge in developing a tumor vaccine
      is effective antigen presentation that elicits anti-tumor immune responses
      without precipitating autoimmunity. Clinical trials must be preceded by
      appropriate animal studies to demonstrate that the concepts can be translated
      into efficacious therapy for cancer. Although many xenograph or transplantable
      tumor models have been used, the most effective studies are in spontaneous tumor
      models. These models are clinically relevant, as tumors arise in an appropriate
      tissue background and in a host conditioned by the physiological events of
      neoplastic progression and tumorigenesis and in the context of a viable immune
      system.

PMID- 11597526
TI  - Laparoscopic radical prostatectomy: irrational exuberance?

PMID- 11597527
TI  - Laparoscopic radical prostatectomy: CON.

PMID- 11597528
TI  - Worldwide experience with alfuzosin and tamsulosin.

PMID- 11597529
TI  - Hand-assisted laparoscopic radical nephrectomy: comparison to open radical
      nephrectomy.
AB  - OBJECTIVES: Hand-assisted laparoscopic surgery is easier to learn than standard
      laparoscopy and simplifies intact specimen removal. We present our experience
      performing hand-assisted laparoscopic radical nephrectomy (HALRN) and compare it
      with contemporary open radical nephrectomy performed at our institution. METHODS:
      We performed 18 HALRNs for renal tumors ranging in size from 2 to 11 cm (average
      4.5). Patients ranged in age from 40 to 83 years (average 62.9). All patients
      underwent HALRN with intact removal through a 7 to 8-cm vertical midline incision
      through an impermeable wound protector. Two or three working ports were used. We
      retrospectively compared our results with the results of 18 open radical
      nephrectomies performed during the same period, with the patients matched for
      age, body mass index, and American Society of Anesthesiologists' score. RESULTS:
      In the HALRN group, the average operating room time was 220.5 minutes, average
      length of stay 3.9 days, average time to return to normal activity 15.8 days, and
      average time to return to work 26.8 days. The median time to return to 100%
      normal was 28.0 days. No conversions or re-explorations were necessary in the
      HALRN series. The final pathologic examination revealed renal cell carcinoma in
      15, oncocytoma in 1, angiomyolipoma in 1, and a complex cyst in 1. At a maximum
      of 48 months of follow-up (average 12.2), no recurrences were identified. Three
      deaths occurred in the series; 2 patients died with no evidence of disease and 1
      patient died of metastatic disease (the nephrectomy was palliative). In the open
      group, the average operating room time was 117.8 minutes, average length of stay
      5.1 days, average time to return to normal activity 23.5 days, and average time
      to return to work 52.2 days. The median time to return to 100% normal was 150
      days, with 3 patients never returning to 100% normal. CONCLUSIONS: Our series
      demonstrated that HALRN is a safe, effective, minimally invasive option for
      treating renal cell carcinoma and provides a shorter hospital stay (P = 0.02),
      earlier return to work (P = 0.04), and earlier return to 100% normal (P = 0.0002)
      than open radical nephrectomy.

PMID- 11597531
TI  - Severely encrusted polyurethane ureteral stents: management and analysis of
      potential risk factors.
AB  - OBJECTIVES: To review the management of heavily encrusted and stuck JJ ureteral
      stents. We report our experience and review current published reports in managing
      heavily encrusted and stuck JJ stents, the guidelines for management, and the
      prevention of such problems. METHODS: We reviewed our stent records from January
      1994 to December 2000 and analyzed our stent complications and their final
      outcome. Fifteen patients had heavily encrusted and stuck stents. Of these, 14
      were encountered in patients with a sizable stone burden (400 to 650 mm(2)) and 1
      occurred in a patient with malignant ureteral obstruction. Sandwich combinations
      of multiple extracorporeal shock wave lithotripsy/traction and endourologic
      procedures were used to render them stone and stent free. The stent was examined
      and the encrustation was analyzed by x-ray crystallography. RESULTS: Of 15
      patients, 13 were available for evaluations; 1 patient was lost to follow-up and
      1 patient died. The average stone burden was 625 mm(2). The encrustation was
      localized to the upper end in eight and to the lower and upper end in three. In 4
      cases, the entire stent was encrusted, and the lumen was occluded in 12. All 13
      patients with stuck, fragmented, and encrusted stents were rendered stone and
      stent free; 2 of the 13 had clinically insignificant residual stones (less than 2
      mm). Calcium phosphate and monohydrate stones were the most commonly encountered
      stone encrustations. CONCLUSIONS: Stent encrustation is one of the most serious
      complications of polyurethane JJ stents. Multimodal endourology should form the
      cornerstone of therapy for heavily encrusted stuck stents. It is important to
      maintain an efficient computerized stent log under the direct supervision of a
      physician. Patients with probable risk factors should be monitored even more
      frequently to avoid mishaps and morbidity.

PMID- 11597530
TI  - Use of glyceryl trinitrate patches in patients with ureteral stones: a
      randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVES: To report a randomized, double-blind, placebo-controlled trial of
      glyceryl trinitrate (GTN) patches. The primary outcome measure was stone passage
      at 6 weeks. GTN is a potent smooth muscle relaxant that may offer benefit by both
      reducing pain and facilitating ureteral stone passage. METHODS: Fifty consecutive
      patients, with a single radiopaque calculus less than 10 mm, were randomized to
      receive a 6-week course of patches containing either 5 mg GTN or placebo.
      Patients used a diary to record pain episodes during the 6-week study period and
      were reviewed weekly with x-ray imaging. Analysis was by intention to treat.
      RESULTS: Twenty-six patients were randomized to the GTN group and 24 to the
      placebo group. Seven patients in the GTN group discontinued therapy because of
      headaches. One patient in the placebo group discontinued because of a skin
      reaction to the patches. No serious adverse events were recorded. No difference
      was observed in the stone-free rate at 6 weeks (18 patients in each group),
      interval to stone passage (median GTN 11.5 days versus placebo 13 days), or
      interventions performed (5 patients each). Although the GTN group reported fewer
      pain episodes (median 3.5 versus 6.0), this did not achieve statistical
      significance. CONCLUSIONS: Our preliminary results did not demonstrate a
      significant advantage in using GTN compared with placebo, with regard to the
      stone-free rate at 6 weeks, interval to stone passage, or number of episodes of
      pain experienced.

PMID- 11597532
TI  - The BTA stat test: a tumor marker for the detection of upper tract transitional
      cell carcinoma.
AB  - OBJECTIVES: To conduct a prospective evaluation to determine the utility of the
      BTA stat test in the detection of upper tract transitional cell carcinoma
      (UTTCC). Monitoring for UTTCC currently relies on invasive procedures such as
      upper tract imaging, ureteral washing cytology (UWC) and/or ureteroscopy, or
      voided urine cytology (VUC). The BTA stat test is a sensitive qualitative
      immunoassay that detects human complement factor H-related protein in voided
      urine. METHODS: A total of 81 patients participated, 27 with histopathologically
      confirmed UTTCC, 26 with upper tract calculi, and 28 with microscopic hematuria
      but no evidence of urologic disease. Voided specimens collected before surgery or
      treatment were tested with the BTA stat test and VUC. UWC was performed in
      specimens collected by a ureteral catheter. RESULTS: The BTA stat test was
      significantly more sensitive and specific than VUC or UWC. The overall
      sensitivity for each was 82%, 11%, and 48%; the specificity was 89%, 54%, and
      33%. The positive predictive value for the BTA stat test was 79% and the negative
      predictive value was 91%, both the highest of the three tests. CONCLUSIONS: The
      BTA stat test was superior to VUC and UWC in the detection of UTTCC. These
      results may support the adoption of a less aggressive follow-up policy when
      monitoring for UTTCC when the BTA stat result is negative. If cystoscopy is
      negative and the BTA stat test is positive, upper tract investigations should be
      expedited and, if the bladder is in place, bladder biopsies performed.

PMID- 11597533
TI  - Treatment of refractory kidney transplant ureteral strictures using balloon
      cautery endoureterotomy.
AB  - OBJECTIVES: To report our long-term clinical results with the use of
      endoureterotomy in patients undergoing renal transplant with a minimum follow-up
      of 23 months. METHODS: Six renal transplant patients developed persistent
      ureteral obstruction demonstrated by elevated serum creatinine levels, renal
      ultrasound, and antegrade pyelography. Stent placement and balloon dilation were
      performed as the initial therapy in all patients. Persistent ureteral obstruction
      was managed with balloon cautery endoureterotomy. Ureteral stents were removed
      cystoscopically 6 weeks after the procedure. RESULTS: Four men and 2 women, mean
      age 45 years (range 38 to 54), underwent eight procedures: six by way of an
      antegrade percutaneous approach and two in an endoscopic retrograde fashion. The
      sites of ureteral stricture were ureterovesical junction (n = 4), ureteropelvic
      junction (n = 1), and midureteroureteral (n = 1). Two patients required a second
      endoureterotomy 3 months after the first attempt. Patients were followed up for a
      mean of 27 months (range 23 to 34). The mean serum creatinine level for all
      patients at follow-up was 2.6 mg/dL (range 1.6 to 3.9), including a mean serum
      creatinine level of 1.8 mg/dL (range 1.6 to 1.9) for nonrejected kidneys and a
      mean of 3.4 mg/dL (range 2.5 to 3.9) in those found to have concurrent rejection.
      Overall, five (63%) of eight procedures were successful in 5 (83%) of 6 patients.
      No intraoperative complications occurred and no blood transfusions were required.
      CONCLUSIONS: Balloon cautery endoureterotomy was successful in this select group
      of renal transplant patients with persistent ureteral strictures after initial
      balloon dilation and stenting failed. This modality proved durable to 27 months
      of follow-up without significant complications.

PMID- 11597534
TI  - Laparoscopic nephrectomy and autotransplantation for severe iatrogenic ureteral
      injuries.
AB  - OBJECTIVES: To evaluate the efficacy of laparoscopic nephrectomy with
      autotransplantation in cases of severe proximal ureteral damage. Many patients
      with complex proximal ureteral injuries have good functional renal parenchyma and
      wish to salvage their kidney. Autotransplantation is a viable alternative to
      nephrectomy in these frustrating situations. METHODS: Two patients, aged 32 and
      36 years, underwent laparoscopic nephrectomy and autotransplantation for
      treatment of severe proximal ureteral injuries. The injuries included a
      ureteropelvic junction avulsion and a proximal ureteral avulsion, respectively.
      Both patients had good functional renal parenchyma. A transperitoneal
      laparoscopic approach was used, and the kidney was removed by way of a Gibson
      incision. RESULTS: The procedures were successful, with immediate return of renal
      function in both patients. A pyeloureterostomy to the native distal ipsilateral
      ureter was required in one and a direct ureterovesical anastomosis was performed
      in the other. In the 2 patients, the warm ischemia time was 4.5 and 4 minutes,
      the transplant operative time 175 and 150 minutes, and the estimated blood loss
      150 and 75 mL, respectively. No intraoperative complications occurred. At follow
      up, the kidneys were functional, and the patients had returned to their normal
      activity. CONCLUSIONS: Laparoscopic nephrectomy with autotransplantation is an
      excellent alternative to nephrectomy or bowel interposition in patients with
      proximal ureteral loss, irrespective of the contralateral renal function. This
      procedure is associated with acceptable morbidity and preserves the renal
      function. This approach is desirable in those patients who have had complications
      from other surgical procedures and are otherwise facing the loss of a normally
      functioning kidney.

PMID- 11597535
TI  - Role of urethrocystoscopy in the evaluation of refractory idiopathic detrusor
      instability.
AB  - OBJECTIVES: To assess the role of diagnostic urethrocystoscopy in the evaluation
      of women with idiopathic detrusor instability (DI) refractory to conventional
      pharmacologic management. METHODS: One hundred consecutive women (mean age 62.1
      +/- 15.1 years) with idiopathic DI refractory to conventional pharmacologic
      management were prospectively enrolled. All patients underwent a meticulous
      evaluation, including a detailed history, urogynecologic questionnaire,
      micturition diary and pad test, urinalysis and culture, physical examination, and
      urodynamic studies. Refractory DI was defined as the lack of clinical improvement
      after at least 6 months of conventional drug therapy. These patients underwent
      additional evaluation with diagnostic urethrocystoscopy. RESULTS: All patients
      had a normal urinalysis and negative cytologic findings. Diagnostic
      urethrocystoscopy revealed isolated bladder tuberculosis in one and transitional
      cell carcinoma in another. Seven other patients had bladder diverticula (only one
      of which was also diagnosed by sonographic examination) and 22 had mild-to
      moderate bladder trabeculations. CONCLUSIONS: The absence of other alarming signs
      (ie, recurrent urinary tract infection, hematuria, significant residual urinary
      volume, positive cytologic findings, or suspicious sonographic findings) cannot
      confirm the lack of significant lower urinary tract abnormalities among patients
      with refractory DI. Diagnostic urethrocystoscopy, a simple and safe office
      procedure, facilitates timely diagnosis and appropriate treatment for these
      patients.

PMID- 11597536
TI  - Combined genitourinary prolapse repair and prophylactic tension-free vaginal tape
      in women with severe prolapse and occult stress urinary incontinence: preliminary
      results.
AB  - OBJECTIVES: Continent patients with a positive stress test demonstrated on
      repositioning of severe genitourinary prolapse are considered to be at high risk
      of developing postoperative symptomatic stress urinary incontinence (SUI). Our
      aim was to evaluate in a prospective study whether a prophylactic, tension-free
      vaginal tape (TVT) procedure, performed during prolapse repair, may prevent the
      development of postoperative SUI in these women. METHODS: Thirty consecutive,
      clinically continent women (mean age 64.5 +/- 9.04 years) with severe
      genitourinary prolapse and occult SUI were prospectively enrolled. Occult SUI was
      defined as a positive stress test with repositioning of the prolapse during the
      preoperative urodynamic studies. All patients had urethral hypermobility; none
      had intrinsic sphincter deficiency. In addition to genitourinary prolapse repair,
      these patients underwent concomitant TVT to prevent postoperative SUI. Patients
      were followed up for at least 1 year. Repeated urodynamic studies were performed
      at 3 to 6 months postoperatively. The main outcome measures were postoperative
      SUI, persistent or de novo detrusor instability, and recurrence of prolapse.
      RESULTS: The mean duration of follow-up was 14.25 +/- 3.08 months (range 12 to
      24). None of the patients developed postoperative symptomatic SUI. However, three
      asymptomatic patients (10%) had a positive stress test during their postoperative
      urodynamic evaluation. Nine patients (30%) had detrusor instability before
      surgery, which persisted in six (66%) postoperatively. Postoperative de novo
      detrusor instability was diagnosed in four other patients (13.33%). None of the
      patients had recurrent urogenital prolapse, nor did they have clinical evidence
      of bladder outlet obstruction. CONCLUSIONS: The preliminary results of TVT as a
      prophylactic procedure in clinically continent women with severe prolapse and
      occult SUI are encouraging. Long-term follow-up is required to confirm the
      durability of these results.

PMID- 11597537
TI  - Tumor progression and survival in patients with T1G3 bladder tumors: multicentric
      retrospective study comparing 94 patients treated during 17 years.
AB  - OBJECTIVES: To compare tumor recurrence, progression, and patient survival in
      T1G3 bladder tumors treated with transurethral resection (TUR) alone, early
      cystectomy, or TUR with an adjuvant 6-week course of bacille Calmette-Guerin
      (BCG) and followed up for a minimum of 5 years. METHODS: Between 1979 and 1996,
      94 patients with T1G3 bladder tumors (lamina propria invasion) were treated at
      nine different centers. The time to tumor recurrence, tumor stage and grade
      progression, number of delayed cystectomies, and patient survival were analyzed
      retrospectively in relation to the initial treatment. RESULTS: The mean follow-up
      was 62 months. Thirty patients were treated by TUR alone (32%), 50 patients by
      TUR plus BCG (53%), and 14 patients by primary cystectomy (15%). The recurrence,
      progression, and cystectomy rates were significantly different between patients
      treated by TUR alone and TUR plus BCG (Fisher's exact test, P = 0.0005, P = 0.02,
      and P = 0.005, respectively). The disease-free survival was also significantly
      different when comparing TUR plus BCG with TUR alone or primary cystectomy
      (Kaplan-Meier analysis, log-rank test, P = 0.02). CONCLUSIONS: Endoscopic
      resection plus BCG treatment of pT1G3 tumors allows an 80% rate of disease-free 5
      year survival with bladder preservation. This conservative option has been widely
      accepted as first-line treatment, offering good cancer control with excellent
      quality of life. Very accurate surgical and pathologic evaluations before
      treatment and lifelong follow-up are obviously required.

PMID- 11597538
TI  - Complications of cystectomy in patients with a history of pelvic radiation.
AB  - OBJECTIVES: To compare the complications occurring during the first year of
      follow-up after radical cystectomy in two groups, one with and one without a
      history of pelvic radiation. Radical cystectomy and urinary diversion is the
      treatment of choice for invasive bladder cancer. METHODS: One hundred ninety-four
      cystectomies were performed between January 1995 and June 2000 by a single
      surgeon. Twenty-three patients were identified with a history of external beam
      radiotherapy to the pelvis (EBRT group), and 23 additional patients without a
      history of pelvic radiation were randomly selected to serve as the control group.
      RESULTS: Although the overall risk of having a complication was not statistically
      different in the EBRT group (48%) than in the control group (30%; P = 0.183),
      complications directly related to surgery were higher in the EBRT group than in
      the control group (48% versus 26%; P = 0.045). The patients in the EBRT group
      were more likely to require an invasive procedure (39% versus 9%; P = 0.018). In
      addition, 5 (22%) of 23 patients in the EBRT group had a symptomatic fluid
      collection, which was diagnosed as a urine leak (n = 2) or an abdominal abscess
      (n = 3). In contrast, no patient in the control group developed a symptomatic
      fluid collection. CONCLUSIONS: Cystectomy after pelvic radiation is associated
      with acceptable morbidity; however, compared with cystectomy performed in a
      nonirradiated pelvis, the risk of complications that will require invasive
      intervention is increased. A history of prior pelvic radiation significantly
      increases the risk of a symptomatic fluid collection.

PMID- 11597539
TI  - Relationship of demographic and clinical factors to free and total prostate
      specific antigen.
AB  - OBJECTIVES: To characterize the role of demographic and clinical parameters in
      the measurements of prostate-specific antigen (PSA), free PSA (fPSA), and percent
      free PSA (%fPSA). METHODS: This was a cohort study of volunteers to a randomized
      screening trial. A central laboratory determined PSA and fPSA for the Prostate,
      Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. A baseline evaluation
      of free and total PSA was done for 7183 white, black, Asian, Hispanic, and other
      male volunteers, aged 55 to 74 years. Comparisons were made across racial and
      ethnic groups and across a set of clinical parameters from a baseline
      questionnaire. RESULTS: The median levels of serum PSA were less than 2.1 ng/mL
      in each age-race grouping of the study participants. The levels of free and total
      PSA were higher in black (n = 868, 12%) participants than in white (n = 4995,
      70%) and Asian (n = 849, 11.8%) participants. Individuals who identified
      themselves as ethnically Hispanic (n = 339, 4.7%) had median PSA levels higher
      than whites who were not Hispanic. The free and total PSA levels increased with
      age, particularly among men 70 to 74 years old. However, the %fPSA levels showed
      less variation among the four racial groups or by age. The free and total PSA
      levels were higher among those who had a history of benign prostatic disease.
      CONCLUSIONS: Demographic (age and race/ethnicity) and clinical (history of benign
      prostatic disease) variables had a moderate effect on the measures of PSA and
      fPSA and very little effect on %fPSA.

PMID- 11597540
TI  - Pilot study of changes in stretched penile length 3 months after radical
      retropubic prostatectomy.
AB  - OBJECTIVES: To evaluate changes in stretched penile length after radical
      retropubic prostatectomy (RRP) in a prospective penile measurement study because
      an occasional complaint from patients after RRP is that their penis is shortened.
      METHODS: Thirty-one patients undergoing RRP by one surgeon were enrolled. The
      same physician completed measurements with a paper ruler to the nearest 0.5 cm.
      The stretched penile length was measured from the tip of the glans to the
      pubopenile skin junction. The measurements were taken in the preoperative holding
      area before the patient received anesthetic medication for the RRP and again 3
      months postoperatively. The reliability and reproducibility of this measurement
      were confirmed. RESULTS: All 31 patients were measured at 3 months
      postoperatively. Of the 31 patients, 22 (71%) had a decrease in stretched penile
      length (range 0.5 to 4.0 cm). Seven were shortened 0.5 cm, 11 were shortened 1.0
      to 2.0 cm, and 4 were shortened more than 2.0 cm. Five patients had no change,
      and in four the penile length was longer (range 0.5 to 1.0 cm). CONCLUSIONS: The
      results of this pilot study appear to show that the stretched penile length
      decreases after RRP at 3 months of follow-up in most men; 48% (15 of 31) had
      considerable shortening greater than 1.0 cm. If confirmed by other investigators,
      the cause of this change needs to be elucidated.

PMID- 11597541
TI  - Prospective patient-reported continence after laparoscopic radical prostatectomy.
AB  - OBJECTIVES: To perform a prospective study using confidential patient-completed
      questionnaires about their urinary habits before and after laparoscopic radical
      prostatectomy. Published reports on urinary continence after radical
      prostatectomy vary depending on the definitions of urinary continence and methods
      of data collection. METHODS: From May 1998 to February 2000, 228 men underwent
      laparoscopic radical prostatectomy for clinically localized prostate cancer. The
      patients were given questionnaires before surgery and at 1, 3, 6, and 12 months
      postoperatively. RESULTS: Before surgery, no patient reported incontinence. At 1,
      3, 6, and 12 months postoperatively, perfect diurnal urinary control (no pads, no
      leakage at all) was reported in 9.9%, 28.6%, 57.4%, and 56.8% of patients,
      respectively. No pads were used in 18.8%, 58.4%, 68.9%, and 78.4% at 1, 3, 6, and
      12 months, respectively. No patient reported use of more than 1 pad daily at 6
      months of follow-up. CONCLUSIONS: Continence after laparoscopic radical
      prostatectomy is comparable to the results after traditional radical retropubic
      prostatectomy. Ongoing use of the laparoscopic route for treating clinically
      localized prostate cancer is warranted.

PMID- 11597542
TI  - Possible use of transrectal power Doppler imaging as an indicator of
      microvascular density of prostate cancer.
AB  - OBJECTIVES: To reveal the possible use of transrectal power Doppler imaging (PDI)
      of the prostate in the assessment of the microvascular density (MVD) of cancer
      lesions. METHODS: In 22 patients with clinically organ-confined prostate cancer,
      PDI was performed before radical prostatectomy and the degree of vascularity of
      the cancer lesions as evaluated by PDI was compared with the MVD determined on
      the surgical specimens. The vascularity by PDI of each cancer lesion was graded
      on a scale of DS0 to DS2, according to the degree of Doppler signal accumulation.
      MVD was obtained using factor VIII immunohistochemistry. RESULTS: The vascularity
      of the PDI of 46 cancer lesions categorized 23 (50%), 10 (22%), and 13 (28%)
      cancer lesions as DS0, DS1, and DS2, respectively. Significant differences were
      found in the MVD between DS0 (46.6 +/- 26.8) and DS2 (89.0 +/- 18.1, P <0.005)
      lesions and between DS1 (50.9 +/- 25.4) and DS2 (P <0.001) lesions. The MVD of 30
      cancer lesions in 13 patients without neoadjuvant therapy was significantly
      higher than that of the 16 lesions in 9 patients with therapy (70.2 +/- 28.2
      versus 39.5 +/- 23.9, P <0.001). In the 13 patients without neoadjuvant therapy,
      the MVD of the DS2 lesions (89.1 +/- 18.9) was significantly higher than that of
      the DS0 lesions (59.3 +/- 32.5, P <0.01) and DS1 lesions (55.9 +/- 20.9, P
      <0.005). CONCLUSIONS: The semiquantitative assessment of Doppler flow signals
      using PDI appears to be of clinical value as an indicator of MVD.

PMID- 11597544
TI  - Prevalence and correlates of erectile dysfunction: results of the Brazilian study
      of sexual behavior.
AB  - OBJECTIVES: To determine the prevalence of erectile dysfunction (ED) and explore
      its potential sociodemographic, medical, and lifestyle correlates. METHODS: While
      attending the "Health Awareness Fair" in nine major cities in Brazil, 1286 men
      completed a questionnaire regarding ED, demographic data, and medical conditions.
      ED was assessed by a single global self-rating question, in which subjects were
      asked to describe themselves as able to achieve and maintain an erection good
      enough for sexual intercourse always, usually, sometimes, or never, and the
      responses were used to classify the subjects as having no, minimal, moderate, or
      complete ED, respectively. Age-adjusted bivariate and multivariate analyses were
      carried out to calculate the prevalence odds ratios and 95% confidence intervals
      for the potential covariates. RESULTS: Overall, 46.2% of men reported some degree
      of ED (minimal 31.5%, moderate 12.1%, complete 2.6%). The prevalence of complete
      ED increased 10 times from 1% to 11% between subjects younger than 40 and older
      than 70 years; moderate ED rose from 8% to 27%, and minimal ED remained constant
      at approximately 31%. In bivariate age-adjusted analyses, low educational
      attainment, black race/ethnicity, homo/bisexuality, and a history of diabetes,
      hypertension, or depression were significantly (P <0.05) associated with an
      increased prevalence of ED. In the multivariate logistic regression model, these
      variables remained significantly associated with ED. CONCLUSIONS: The results of
      our study show that ED is a major health problem in Brazil and both the severity
      and prevalence increase with age. The medical, sociodemographic, and lifestyle
      variables associated with ED may alert physicians to patients who are at risk of
      ED, as well as offer clues to the etiology of ED.

PMID- 11597543
TI  - Effective long-term androgen suppression in men with prostate cancer using a
      hydrogel implant with the GnRH agonist histrelin.
AB  - OBJECTIVES: To evaluate the effectiveness of a hydrogel implant containing the
      gonadotropin-releasing hormone (GnRH) agonist histrelin in suppressing
      testosterone production in men with prostate cancer and to determine the
      effective dose (one, two, or four implants). METHODS: Forty-two men with prostate
      cancer and indications for androgen ablation were treated with one, two, or four
      implants. In two of the clinics, comprising 27 subjects, the treatment period was
      12 months, with replacement with the same number of implants at 12-month
      intervals. In a third clinic, which treated 15 subjects, the implants were left
      in place for up to 30 months. The total experience was 605 treatment months.
      RESULTS: The histrelin levels were detected in serum proportional to the number
      of implants placed. The response, however, was similar among all three dose
      levels, with testosterone and luteinizing hormone essentially completely
      suppressed. Serum testosterone levels decreased from 21.9 +/- 17.6 nmol/L to 0.93
      +/- 1.57 nmol/L within 1 month and were maintained at 0.55 +/- 0.24 nmol/L at 6
      months and 0.60 +/- 0.28 nmol/L after 12 months of treatment. Of the 38
      assessable patients, 35 (92%) had castrate levels of testosterone within 4 weeks
      of the initial implant placement. All patients followed for up for 12 months
      after placement of the initial set of implants maintained suppression of
      testosterone production while the implant was in place. CONCLUSIONS: The
      histrelin hydrogel implant provided adequate and reliable delivery of the potent
      GnRH agonist histrelin during at least 1 year using a single implant in men with
      prostate cancer. No apparent advantages were found in using more than one
      implant, and the question of the possible effectiveness of even lower doses
      remains open. This treatment modality appears to be both safe and effective.

PMID- 11597545
TI  - Interactions of sildenafil and tacrolimus in men with erectile dysfunction after
      kidney transplantation.
AB  - OBJECTIVES: To study the pharmacokinetics of the combined use of sildenafil
      (which may provide an effective treatment for patients with erectile dysfunction
      after kidney transplantation) and tacrolimus, as interactions between them are
      expected because of a common elimination pathway. METHODS: Ten male patients (age
      29 to 52 years) were included. Because of its importance in transplant
      recipients, medication remained unchanged. On day 1, tacrolimus was administered
      routinely, and blood samples for tacrolimus assays were drawn at predefined
      times. On day 2, sildenafil was added and blood was collected for assays of
      tacrolimus, sildenafil, and the sildenafil metabolite UK103,320 (UK) at the
      indicated times. Blood pressure was monitored on both study days. Sildenafil and
      UK were assessed by high-pressure liquid chromatography and tacrolimus was
      assessed by microparticle enzyme immunoassay. RESULTS: No effects of sildenafil
      on the tacrolimus pharmacokinetics were found. However, in the patients studied,
      the sildenafil and UK pharmacokinetics were altered compared with the results of
      previous studies. The mean peak concentration of sildenafil was higher by 44% and
      the area under the concentration-time data increased by 90%. The elimination half
      life was prolonged (4.7 hours compared with 3 hours in healthy volunteers). The
      area under the concentration-time data for UK was about threefold larger than in
      healthy volunteers, and the half-life was prolonged from 3.8 hours to 11.4 hours.
      Pronounced blood pressure drops were observed. CONCLUSIONS: Tacrolimus or the
      concomitant medication or the disease itself might have altered the sildenafil
      and UK pharmacokinetics. Because of the drop in blood pressure, sildenafil
      therapy should start at the lowest dose and any antihypertensive medication
      should be adjusted.

PMID- 11597546
TI  - Intraoperative nerve stimulation predicts postoperative potency.
AB  - OBJECTIVES: Intraoperative nerve stimulation has been used to map the course of
      cavernosal nerve bundles to aid in nerve-sparing radical prostatectomy (RP). We
      sought to determine whether the intraoperative nerve stimulation response after
      removal of the prostate specimen predicts postoperative potency. METHODS: We
      prospectively evaluated 63 consecutive patients undergoing RP. Among these 63
      patients, 41 patients had a bilateral nerve-sparing procedure, and 22 underwent
      bilateral wide resection of the neurovascular bundles. Potency was determined at
      1 year by direct patient interview. RESULTS: Of the 22 patients with wide
      resection, 16 (73%) had no observed stimulated response, 4 (18%) had a measurable
      tumescence response, and 2 (9%) had detumescence. All 22 patients were impotent
      postoperatively. At a minimum follow-up of 1 year, of the 41 patients who
      underwent nerve-sparing RP, 27 (66%) had postoperative erections sufficient for
      penetration. Of the 30 men with an intraoperative stimulated tumescence response,
      24 (80%) were potent; of the 6 with a detumescence response, 2 (33%) were potent;
      and of the 5 with no stimulated nerve response, 1 (20%) was potent. A tumescence
      response was significantly more predictive of postoperative potency than no
      intraoperative response (P = 0.017). CONCLUSIONS: An intraoperative tumescence
      response with stimulation of the neurovascular bundles after prostate specimen
      removal is more likely to correspond to successful postoperative sexual function
      after nerve-sparing RP than is no response.

PMID- 11597547
TI  - Is routine urinary tract investigation necessary for children with
      monosymptomatic primary nocturnal enuresis?
AB  - OBJECTIVES: To investigate in a prospective study the role of bladder function
      and to compare the results of urinary tract ultrasonography and urinalysis in
      children with and without primary nocturnal enuresis because, although this is a
      common problem in children, the etiology and mechanisms of the disorder have not
      been elucidated. METHODS: The study included 106 children with monosymptomatic
      primary nocturnal enuresis and a control group of 57 children with no history of
      voiding dysfunction, aged 5 to 19 years. All children underwent urinalysis,
      bladder and upper urinary tract ultrasonography, and uroflowmetry. The bladder
      capacity, bladder wall thickness, and postvoid residual volume were measured
      using ultrasonography. The findings were compared between the enuresis and
      control groups according to age: 5 to 9 years, 10 to 14 years, and 15 to 19
      years. RESULTS: The mean age was 9.6 +/- 3.1 years in the nocturnal enuresis
      group and 9.4 +/- 3.3 years in the control group (P = 0.727). The mean number of
      defecations per week was significantly lower statistically in the enuresis group
      than in the control group in the age categories of 5 to 9 years and 10 to 14
      years (P = 0.038 and P = 0.018, respectively), and the mean number of urinations
      per day was significantly higher statistically in the enuresis group than in the
      control group in the age groups of 5 to 9 years and 10 to 14 years (P = 0.002 and
      P = 0.001, respectively). The bladder capacity, bladder wall thickness, postvoid
      residual volume, uroflowmetry maximal flow rate, and average flow rate were not
      significantly different statistically between the children with primary nocturnal
      enuresis and the control group in the three age brackets. Urinary infection was
      detected in 2 children (1.88%) in the nocturnal enuresis group and none of the
      children in the control group (P = 0.547). Upper urinary tract abnormalities
      detected by ultrasonography were seen in 3 children (2.83%) in the nocturnal
      enuresis group and 1 child (1.75%) in the control group, revealing no statistical
      significance (P = 0.671). CONCLUSIONS: Our findings show that the
      ultrasonographic and uroflowmetry findings on bladder function and the upper
      urinary system and the incidence of urinary infection are similar in children
      with and without nocturnal enuresis. Obtaining a voiding and elimination diary in
      conjunction with a good history may be beneficial in children with
      monosymptomatic primary nocturnal enuresis. In addition, routine urinalysis may
      be unnecessary in the evaluation of children with monosymptomatic primary
      nocturnal enuresis after obtaining a careful and complete history of the voiding
      dysfunction.

PMID- 11597549
TI  - Plastibell template circumcision: a new technique.
AB  - A novel circumcision technique using the Plastibell as a template is described.
      This technique is fast and ensures excellent cosmesis compared with the standard
      sleeve circumcision. It is easy to perform and allows the urologist to achieve
      consistently excellent cosmetic results. We describe the technique in detail.

PMID- 11597550
TI  - Massive extracellular tryptase from activated bladder mast cells in interstitial
      cystitis.

PMID- 11597551
TI  - Massive hematuria due to right renal artery mycotic pseudoaneurysm in a patient
      with subacute bacterial endocarditis.
AB  - A 40-year-old woman with recently diagnosed bacterial endocarditis was admitted
      to the hospital with gross hematuria and anemia. Computed tomography revealed a
      large right upper pole renal artery pseudoaneurysm, a wedge-shaped hypoperfused
      region of the left kidney, and a splenic abscess. Radiographic embolization of
      the right renal artery was performed to stabilize the bleeding. The splenic
      abscess was drained. Subsequent right nephrectomy and splenectomy were performed
      for persistent leukocytosis. This unusual presentation of a septic embolus and
      its management are discussed.

PMID- 11597553
TI  - Nonvisualization of intravenous methylene blue in patients with clinically normal
      renal function.
AB  - Urologists use intravenous dyes in diagnosing genitourinary fistulas and in
      investigating ureteral patency. Methylene blue and indigo carmine are the most
      common dyes used today. Generally, patients with clinically normal renal function
      demonstrate dye in their urine after several minutes. We report on 2 patients in
      whom methylene blue was not visualized after intravenous injection. A review of
      urologic and pharmacologic published reports led to a possible explanation for
      this phenomenon. Methylene blue can metabolize into leukomethylene blue, which is
      colorless in urine. Indigo carmine, however, is not readily metabolized but is
      rather freely filterable by the kidneys. Therefore, it is important to appreciate
      that nonvisualization of methylene blue may be a metabolism effect and not an
      anatomic one.

PMID- 11597552
TI  - Delayed nephrectomy in grade V renal injury with two interesting anatomic
      variations.
AB  - The decision to perform early nephrectomy in hemodynamically stable grade V
      injury rather than to provide supportive nonoperative care is not universally
      accepted. The management of isolated grade V renal injury, as well as the
      management of coexisting abdominal trauma that requires operative intervention,
      is an area of controversy. We present the case of a grade V renal injury that was
      initially managed expectantly at a level I trauma center. After transfer to our
      facility, nephrectomy was performed. The case illustrates the merit of prompt
      definitive surgical treatment.

PMID- 11597554
TI  - Aspirin treatment improves bladder function after outlet obstruction in rabbits.
AB  - OBJECTIVES: To examine whether bladder smooth muscle dysfunction after outlet
      obstruction could be altered by treatment with aspirin. Long-term outlet
      obstruction causes contractile and metabolic dysfunction of the bladder in vivo
      and in vitro. The evidence is growing that a decrease in bladder perfusion is an
      important cause of this phenomenon. The platelet aggregation inhibitor,
      acetylsalicylic acid (aspirin), has been used to improve perfusion of the heart
      for decades. METHODS: Ten male New Zealand white rabbits were obstructed for 4
      weeks. Five rabbits received no further treatment (Obs), and 5 rabbits received 2
      mg/kg/day aspirin (Obs+aspirin), administered by an osmotic pump implanted
      subcutaneously 1 week before the surgical obstruction. The bleeding time was
      measured to confirm the effectiveness of the aspirin treatment. Three different
      control groups were created: sham-operated rabbits, unobstructed rabbits with
      pumps containing DMSO (vehicle), and unobstructed rabbits with pumps containing
      aspirin. The contractile responses of bladder strips to field stimulation,
      adenosine triphosphate, carbachol, and KCl were determined. A section of each
      detrusor tissue was fixed in formalin and used to determine the smooth muscle and
      collagen (connective tissue) volume fraction. RESULTS: No differences were found
      in the bladder weights or responses to stimuli in the different control groups,
      which were therefore combined. Partial bladder outlet obstruction caused
      significant increases in the bladder weight of the obstructed animals
      (Obs+aspirin, 10.15 +/- 0.87 g; Obs, 10.17 +/- 0.88 g; and controls, 2.87 +/-
      0.21 g). The aspirin treatment increased the bleeding time from 1.7 +/- 0.3
      minutes to 3.3 +/- 0.1 minutes. The responses to field stimulation were
      significantly reduced in all of the obstructed rabbits. However, the responses of
      the bladder strips from the Obs rabbits to field stimulation were impaired to a
      significantly greater degree than were those from the Obs+aspirin rabbits. The
      response to 32-Hz stimulation was reduced by 86% in the Obs group but by only 64%
      in the Obs+aspirin group. The responses to carbachol were significantly reduced
      by 62% in the strips from the Obs rabbits, but the responses of the strips from
      the Obs+aspirin rabbits were similar to the responses of the strips from the
      controls. The responses to KCl and adenosine triphosphate were reduced, although
      they just failed to achieve statistical significance using Bonferroni's analysis.
      The ratio of smooth muscle and connective tissue shifted slightly toward smooth
      muscle after 4 weeks of obstruction, but no difference was found with or without
      aspirin treatment. CONCLUSIONS: Low-dose aspirin has a small but significant
      protective effect on the contractile dysfunction induced by bladder outlet
      obstruction in rabbits, although the increase in bladder mass was not altered.
      Bladders of the same weight showed improved responses to all forms of stimulation
      after pretreatment with aspirin. Already used by millions of patients with heart
      diseases, aspirin could be a useful protection against contractile dysfunction of
      the obstructed bladder.

PMID- 11597555
TI  - Plasma levels of IGF-1, IGF-2, and IGFBP-3 in white and African-American men at
      increased risk of prostate cancer.
AB  - OBJECTIVES: To further investigate the relationship between the plasma levels of
      insulin-like growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2),
      insulin-like growth factor binding protein-3 (IGFBP-3), growth hormone,
      testosterone, and demographic factors, particularly race, within a group of men
      at increased risk of prostate cancer development. METHODS: Enzyme-linked
      immunosorbent assays or an immunosorbent assay was used to quantitate the plasma
      levels of IGF-1, IGF-2, IGFBP-3, growth hormone, and testosterone. The study
      group consisted of 169 men (85 African-American, 84 white) aged 35 to 69 years,
      with no personal history of prostate cancer, but having at least one first-degree
      relative diagnosed with the disease, unless they were African-American. The
      relationships between the plasma levels and the categorical covariates were
      assessed using the nonparametric Wilcoxon test and between the continuous
      variables using Spearman's correlation coefficient. RESULTS: The mean plasma
      levels of IGFBP-3 were significantly lower in African-American (2657 ng/mL) than
      in white (2965 ng/mL) men (P = 0.0062). The plasma levels of IGF-2 were also
      lower in the African-American (503.5 ng/mL) than in the white (549.1 ng/mL) men
      (P = 0.0084). Overall, the IGF-1 plasma levels correlated positively with the IGF
      2, IGFBP-3, and growth hormone levels and the IGF-2 plasma levels correlated
      negatively with the testosterone levels. CONCLUSIONS: Our results demonstrate
      that lower plasma levels of IGFBP-3 and IGF-2 are associated with race in a
      population of men at increased risk of developing prostate cancer. The ability of
      these markers to predict earlier disease onset is currently under investigation.

PMID- 11597557
TI  - Hand-assisted demucosalized gastrocystoplasty comparing different tissue closure
      methods.
AB  - OBJECTIVES: To perform experiments to determine whether a new tissue sealant
      (SynthaSeal) could be an alternative for suture closure in minimally invasive
      bladder autoaugmentation gastrocystoplasty using demucosalized stomach.
      Alternative methods to suture closure for tissue approximation such as laser
      tissue welding and fibrin glue have been reported. METHODS: Minimally invasive
      autoaugmentation gastrocystoplasty with demucosalized stomach was performed on 14
      female mongrel dogs. Two dogs were used to refine the technique. The remaining
      dogs were assigned to a suture group (n = 6) or a SynthaSeal group (n = 6).
      Anastomoses were performed using either SynthaSeal or suture. The in vivo bladder
      volumes and pressures of the groups were measured before and after
      gastrocystoplasty. The animals were studied on day 14. Samples of the anastomotic
      area were taken to measure the tensile strength and stress. Histologic analysis
      was conducted to assess tissue healing. The anastomotic time was recorded for
      each group. RESULTS: The tensile strength of the anastomoses in the SynthaSeal
      group was significantly increased (9.99 +/- 1.14 Newtons) compared with the
      suture group (5.66 +/- 0.97 Newtons) (P <0.05). The breaking stress comparisons
      and anastomosis times were equivalent between the two groups. The histologic
      evaluation revealed minor tissue devitalization and a normal inflammatory
      response in both groups. CONCLUSIONS: Minimally invasive gastrocystoplasty using
      demucosalized stomach can be successfully performed with SynthaSeal tissue
      sealant. This may provide a reliable alternative to suture closure.

PMID- 11597556
TI  - p63 protein expression is rare in prostate adenocarcinoma: implications for
      cancer diagnosis and carcinogenesis.
AB  - OBJECTIVES: To examine the expression of the p63 protein in normal,
      preneoplastic, and neoplastic human prostatic tissue. The p63 gene, a member of
      the p53 gene family, is expressed in the basal epithelial cells of multiple
      organs. Irregularities in p63 expression have been associated with epithelial
      carcinogenesis. METHODS: We performed immunohistochemistry with an anti-p63
      antibody on specimens from radical prostatectomies, prostate needle biopsies, and
      metastatic prostate adenocarcinoma. We analyzed p63 expression in regions of
      normal prostate, benign prostatic hyperplasia, proliferative inflammatory atrophy
      (PIA), high-grade intraepithelial neoplasia, and adenocarcinoma. RESULTS: Basal
      epithelial cells in normal, benign prostatic hyperplasia, and high-grade
      intraepithelial neoplasia tissue stained intensely for the p63 polypeptide, but
      the vast majority of adenocarcinoma specimens from 233 patients-66 (94%) of 70
      radical prostatectomies, 132 (89%) of 148 prostate needle biopsies, and 14 (93%)
      of 15 metastases-did not. In tumors in which the adenocarcinoma cells were
      positive, the staining intensity was weak and occurred in less than 1% of the
      cells. Tumors that stained positive for p63 were more likely to be high grade
      than those that did not (P <0.0001). Basal cells in PIA expressed p63, but these
      cells were sparsely distributed relative to the basal cells in the normal glands.
      Luminal cells in PIA were, in general, negative for p63. CONCLUSIONS: In contrast
      to normal and preneoplastic prostatic tissue, the vast majority of prostate
      adenocarcinomas do not express p63. Therefore, p63 immunohistochemistry
      represents a potential novel adjuvant method for facilitating the pathologic
      diagnosis of prostate cancer in prostate needle biopsies. The selective
      expression of p63 in normal basal cells, coupled with the finding that p63 null
      mice fail to develop prostates, provides strong evidence that the basal cells
      represent prostatic epithelial stem cells. In addition, these findings suggest
      that p63 may protect prostatic epithelial cells against neoplastic transformation
      and support the hypothesis that intermediately differentiated cells in the
      luminal epithelium of PIA are the targets of neoplastic transformation in the
      prostate.

PMID- 11597558
TI  - Urolithiasis on the Byzantine throne.

PMID- 11597559
TI  - Technique determines efficacy of local anesthetic for outpatient prostate biopsy.

PMID- 11597560
TI  - Laparoscopic gonadectomy and excision of Mullerian remnant in an adult intersex
      patient.

PMID- 11597562
TI  - Do the eastern and northern parts of The Netherlands differ in testicular cancer?

PMID- 11597564
TI  - Noninvasive urodynamic evaluation of bladder outlet obstruction using Doppler
      ultrasonography.

PMID- 11597566
TI  - Symptomatic ureteropelvic junction obstruction in children.

PMID- 11597567
TI  - Atomic force microscopy as a novel pharmacological tool.
AB  - With the advent of the atomic force microscope (AFM), the study of biological
      samples has become more realistic because, in most cases, samples are not covered
      or fixed, which makes it possible to observe them while the cells are alive. This
      advantage of the AFM allowed the advent of a new invention: nanobiosensors using
      the cantilever (probe) of the AFM and, in this case, it is possible to observe
      the entering or exiting of specific molecules (including medications) from living
      cells. This is the smallest biosensor in the world, measuring about 100 microm
      long (about the width of a hair). Beyond sensing the area of interest with this
      biosensor, it is also possible to see the area and exactly what is occurring on
      it, in real time. This new tool will be very useful for several areas: molecular
      pharmacology, enzymology, physiology, molecular biology, biotechnology,
      biophysics, physical chemistry, analytical chemistry, and organic chemistry. This
      article discusses, mainly, the applications of this new technique to the field of
      pharmacology.

PMID- 11597568
TI  - Cellular pharmacology of cerulenin analogs that inhibit protein palmitoylation.
AB  - S-palmitoylation is a dynamic post-translational modification of certain
      proteins, which helps determine membrane association and may function to enhance
      the interactions of signaling molecules with their activated receptors and
      effector systems. Unlike enzymes that catalyze other protein lipidation
      reactions, e.g. farnesylation and N-myristoylation, protein palmitoyltransferase
      is virtually uncharacterized biochemically. We have described previously the
      synthesis of cerulenin analogs including cis-2,3-epoxy-4-oxononadecanamide (16C)
      and cis-2,3-epoxy-4-oxododecanamide (9C) that inhibit protein palmitoylation
      (Lawrence et al., J Med Chem 1999;42:4932-41), most likely through covalent
      alkylation of protein palmitoyltransferase. [3H]9C and [3H]16C were prepared by
      catalytic incorporation of 3H2 into unsaturated precursors for further study of
      their cellular pharmacology. After 4 hr, T24 bladder carcinoma cells in the
      absence of serum accumulated a 4-fold higher intracellular level of [3H]16C than
      of [3H]9C. Uptake of [3H]9C and [3H]16C was reduced by the presence of serum in
      the medium, suggesting their binding to serum proteins. [3H]9C and [3H]16C
      alkylated unique patterns of proteins in T24 cells, with proteins of
      approximately 80 and 31 kDa being labeled by each compound. A panel of human
      tumor cell lines demonstrated half-maximal proliferation inhibition at
      concentrations of 7-30, 4-16, and 8-36 microM, for cerulenin, 9C, and 16C,
      respectively, indicating that the cell lines have approximately equal sensitivity
      to these compounds. Different cell lines have similar patterns of protein
      alkylation by [3H]9C or [3H]16C, with labeling intensity related to cytotoxicity
      of the compounds. Since both 9C and 16C inhibit palmitoylation, the commonly
      labeled proteins are candidates for human protein palmitoyltransferase.

PMID- 11597569
TI  - Sequestration and phosphorylation of the prostaglandin E2 EP4 receptor:
      dependence on the C-terminal tail.
AB  - The prostaglandin E2 (PGE2) EP4 subtype is one of four prostanoid receptors that
      use PGE2 as the preferred ligand. We have investigated the agonist-mediated
      regulation of EP4 using a multifaceted approach. Short-term (30 min) agonist
      challenge of recombinant EP4 expressed in human embryonic kidney 293 cells (EP4
      HEK293 cells) with PGE2 (1 microM) resulted in the desensitization of
      intracellular cyclic AMP (cAMP) accumulation and a reduction in cell surface
      [3H]PGE2 specific binding sites. These events correlated with sequestration of
      EP4, as visualized by immunofluorescence confocal microscopy and phosphorylation,
      as shown by [32P]orthophosphate labeling of the receptor. Stimulation of protein
      kinase A activity in EP4-HEK293 cells (10 microM forskolin or 1 mM 8-bromo-cAMP)
      did not induce EP4 desensitization, sequestration, or phosphorylation. In
      contrast, stimulation of protein kinase C activity (100 nM phorbol 12-myristate
      13-acetate) attenuated PGE2-induced adenylyl cyclase activity and increased EP4
      phosphorylation, but did not induce sequestration or a reduction in [3H]PGE2
      specific binding sites. EP4 receptors containing a third intracellular loop
      deletion [EP4 (del. 215-263)] or a carboxyl-terminal tail truncation [EP4 (del.
      355)] of EP4 were used to demonstrate that the C-terminal tail governs
      sequestration as well as phosphorylation of the receptor.

PMID- 11597570
TI  - Cisplatin-induced apoptosis by translocation of endogenous Bax in mouse
      collecting duct cells.
AB  - cis-platinum(II) (cis-diammine dichloroplatinum; cisplatin) is a potent antitumor
      compound that is widely used for the treatment of many malignancies. An important
      side-effect of cisplatin is nephrotoxicity, which results from injury to renal
      tubular epithelial cells and can be manifested as either acute renal failure or a
      chronic syndrome characterized by renal electrolyte wasting. Recently, apoptosis
      has been recognized as an important mechanism of cell death mediating the
      antitumor effect of cisplatin. This study was undertaken to examine the
      mechanisms of cell death induced by cisplatin in M-1 cells, which were derived
      from the outer cortical collecting duct cells of SV40 transgenic mice. Treatment
      of M-1 cells with high concentrations of cisplatin (0.5 and 1 mM) for 2 hr led to
      necrotic cell death, whereas a 24-hr treatment with 5-20 microM cisplatin led to
      apoptosis. Antioxidants protected against cisplatin-induced necrosis, but not
      apoptosis, indicating that reactive oxygen species play a role in mediating
      necrosis but not apoptosis induced by cisplatin and that the mechanism of cell
      death induced by cisplatin is concentration dependent. The low concentrations of
      cisplatin, which induced apoptosis in M-1 cells, did not affect the expression
      levels of Bcl-2-related proteins and did not activate c-Jun NH2-terminal kinase
      (SAPK/JNK). Cisplatin induced the translocation of endogenous Bax from the
      cytosolic to the membrane fractions and, subsequently, the release of cytochrome
      c. Overexpression of Bcl-2 blocked cisplatin-induced apoptosis and Bax
      translocation. These observations suggest that the subcellular redistribution of
      Bax is a critical event in the apoptosis induced by cisplatin.

PMID- 11597571
TI  - Induction of CYP2B1/2 and nicotine metabolism by ethanol in rat liver but not rat
      brain.
AB  - A higher proportion of alcoholics than non-alcoholics smoke (>80 vs 30%). In
      animals, chronic administration of alcohol induces tolerance to some effects of
      nicotine. To investigate if chronic ethanol (EtOH) induces alterations in
      CYP2B1/2 and nicotine C-oxidation activity, male rats (N = 4-6/group) were
      treated once daily with saline or EtOH (0.3, 1.0, and 3.0 g/kg, p.o./by gavage)
      for 7 days. A quantitative immunoblotting assay was developed to detect CYP2B1/2
      in the brain, where constitutive expression is low, and in the liver. Using this
      method, it was determined that EtOH did not alter CYP2B1/2 protein expression
      significantly in six brain regions (olfactory bulbs, olfactory tubercles, frontal
      cortex, hippocampus, cerebellum, and brainstem). However, a dose-dependent
      induction of CYP2B1/2 protein expression was detected in the liver. Significant
      induction of 2-, 3-, and 2.7-fold were observed for the 0.3, 1.0, and 3.0 g/kg
      doses, respectively. Increases were also observed in CYP2B1 mRNA, which was
      induced by 14, 38, and 43% at the same doses. Liver microsomal nicotine C
      oxidation also was increased (1.3 to 4.5-fold). CYP2B selective inactivators
      demonstrated that approximately 70% of nicotine C-oxidation was mediated by
      CYP2B1/2 in both EtOH-induced and uninduced hepatic microsomes. In summary,
      chronic, behaviorally relevant doses of EtOH induce CYP2B1/2 protein, mRNA, and
      nicotine C-oxidation activity in rat liver but not in rat brain, and these
      increases could contribute to cross-tolerance and co-abuse of ethanol and
      nicotine.

PMID- 11597572
TI  - Roles of long chain fatty acids and carnitine in mitochondrial membrane
      permeability transition.
AB  - Palmitoyl-CoA (Pal-CoA) lowered the respiratory control ratio (RCR), and induced
      mitochondrial membrane permeability transition (MPT) and cytochrome c (Cyt. c)
      release from isolated rat liver mitochondria. L-Carnitine suppressed the Pal-CoA
      induced dysfunction, MPT, and Cyt. c release of isolated mitochondria. This
      suppression was inhibited by cephaloridine, an inhibitor of carnitine uptake into
      mitochondria. Cyclosporin A (CsA), an inhibitor of MPT, and BSA also suppressed
      the Pal-CoA-induced MPT. In the presence of inorganic phosphate (P(i)), Ca2+
      induced MPT was suppressed by BSA, L-carnitine, and chlorpromazine, an inhibitor
      of phospholipase A2. In the presence of a low concentration of Ca2+, 3,3',5
      triiodothyronine, long chain fatty acids, salicylic acid, and diclofenac induced
      MPT by a mechanism that was suppressed by BSA, L-carnitine, or chlorpromazine.
      During the incubation of mitochondria on ice, their respiratory competence
      decreased; L-carnitine and BSA also prevented this decrease. Mitochondrial
      depolarization in pheochromocytoma PC12 cells was induced by either serum
      deprivation or arachidonic acid by a mechanism that was suppressed by acetyl-L
      carnitine. These results indicate that some MPTs may be regulated by fatty acid
      metabolism and that the Pal-CoA-induced MPT plays an important role in the
      induction of apoptosis.

PMID- 11597573
TI  - Domains of the parathyroid hormone (PTH) receptor required for regulation by G
      protein-coupled receptor kinases (GRKs).
AB  - To investigate the domains of the parathyroid hormone (PTH) receptor required for
      regulation by G protein-coupled receptor kinases (GRKs), we created mutant PTH
      receptors lacking potential GRK-phosphorylation sites. Mutant #1 was truncated at
      amino acid 544 and, therefore, lacked nine hydroxyl group-containing amino acids
      at the C-terminus. In mutant #2, we replaced threonines 392 and 399 in the third
      intracellular loop with glycines. Co-transfection of HEK293 cells with the wild
      type receptor and either GRK2, GRK3, or GRK5 inhibited PTH-induced cyclic (cAMP)
      generation; co-transfection of GRK4 or GRK6 had no effect on PTH receptor
      responsiveness. GRK2-mediated inhibition of PTH receptor signaling was associated
      with enhanced phosphorylation receptor proteins. Co-expression of GRK2 similarly
      reduced PTH-induced cAMP generation by the wild-type receptor and mutant #1, and
      caused phosphorylation of receptor proteins to a similar extent. Co-expression of
      GRK2 had little effect on PTH-induced cAMP generation by mutant #2 but enhanced
      agonist-induced phosphorylation of mutant #2 compared with that of either the
      wild-type receptor or mutant #1. Enhanced phosphorylation of mutant #2 was
      associated with a reduction in agonist-induced internalization of mutant #2
      compared with the wild-type receptor. Thus, phosphorylation of mutant #2 failed
      to cause receptor desensitization and inhibited receptor internalization. These
      data are consistent with the notion that: (a) GRKs contribute to regulating PTH
      receptor responsiveness, and (b) domains in the third intracellular loop are not
      required for agonist-induced phosphorylation of PTH receptors, but are critical
      for both agonist-induced internalization of PTH receptors and GRK2-mediated
      regulation of PTH receptor signaling.

PMID- 11597574
TI  - Catalytic inhibition of human DNA topoisomerase IIalpha by hypericin, a
      naphthodianthrone from St. John's wort (Hypericum perforatum).
AB  - St. John's wort (Hypericum perforatum) is the most widely used herbal medicine
      for the treatment of depression. However, concerns have arisen about the
      potential of its interaction with other drugs due to the induction of cytochrome
      P450 isozymes 1A2 and 3A4 by the components hypericin and hyperforin,
      respectively. Structurally similar natural products are often employed as
      antitumor agents due to their action as inhibitors of DNA topoisomerases, nuclear
      enzymes that modify DNA during cellular proliferation. Preliminary findings that
      hypericin inhibited the DNA relaxation activity of topoisomerase IIalpha (topo
      II; EC 5.99.1.3) led us to investigate the mechanism of enzyme inhibition. Rather
      than stabilizing the enzyme in covalent complexes with DNA (cleavage complexes),
      hypericin inhibited the enzyme prior to DNA cleavage. In vitro assays indicate
      that hypericin is a potent antagonist of cleavage complex stabilization by the
      chemotherapeutics etoposide and amsacrine. This antagonism appears to be due to
      the ability of hypericin to intercalate or distort DNA structure, thereby
      precluding topo II binding and/or DNA cleavage. Supporting its non-DNA damaging,
      catalytic inhibition of topo II, hypericin was shown to be equitoxic to both wild
      type and amsacrine-resistant HL-60 leukemia cell lines. Moreover, hypericin was
      incapable of stimulating DNA damage-responsive gene promoters that are activated
      by etoposide. As with the in vitro topo II assay, antagonism of DNA damage
      stimulated by 30 microM etoposide was evident in leukemia cells pretreated with 5
      microM hypericin. Since many cancer patients experience clinical depression and
      concomitantly self-medicate with herbal remedies, extracts of St. John's wort
      should be investigated further for their potential to antagonize topo II-directed
      chemotherapy regimens.

PMID- 11597575
TI  - Inhibition of phosphoenolpyruvate carboxykinase (PEPCK) gene expression by
      troglitazone: a peroxisome proliferator-activated receptor-gamma (PPARgamma)
      independent, antioxidant-related mechanism.
AB  - Phosphoenolpyruvate carboxykinase (PEPCK) is the rate-limiting enzyme of
      gluconeogenesis. Enhanced expression of the PEPCK gene in liver is present in
      most models of diabetes, and is thought to contribute to the increased hepatic
      glucose output seen in this disease. Recently, we showed that troglitazone, the
      first thiazolidinedione (TZD) used clinically, inhibits expression of the PEPCK
      gene in isolated hepatocytes. We have pursued the molecular mechanism whereby
      troglitazone exerts this inhibition. TZDs are known to bind and activate
      peroxisome proliferator-activated receptor-gamma (PPARgamma), a nuclear receptor,
      which regulates expression of target genes. Initially, we examined the abilities
      of three other TZDs (rosiglitazone, englitazone, and ciglitazone) to inhibit
      expression of the PEPCK gene. Despite the fact that these agents are ligands for
      PPARgamma, they displayed little if any inhibitory activity on the expression of
      this gene. GW1929 [N-(2-benzoyl phenyl)-l-tyrosine], another potent PPARgamma
      ligand that is unrelated structurally to TZDs, had no inhibitory effect on PEPCK
      gene expression, while a natural PPARgamma ligand, the prostaglandin metabolite
      15-PGJ2 (15-deoxy-Delta(12,14)-prostaglandin J2), displayed only modest
      inhibitory activity. Treatment of hepatocytes with ligands for other isoforms of
      PPAR also had no significant effect on PEPCK gene expression. Troglitazone has an
      alpha-tocopherol (vitamin E) moiety that is not present in other TZDs, and
      treatment of hepatocytes with vitamin E led to an inhibition of PEPCK gene
      expression. These observations support the conclusion that troglitazone inhibits
      the expression of the PEPCK gene by a PPARgamma-independent, antioxidant-related
      mechanism.

PMID- 11597576
TI  - Stimulation of gap junctional intercellular communication by thalidomide and
      thalidomide analogs in human fetal skin fibroblasts (HFFF2) and in rat liver
      epithelial cells (WB-F344).
AB  - Gap junction channels maintain cell-cell communication and are essential for the
      coordination of tissues, playing a pivotal role in embryonal development. Gap
      junctional intercellular communication (GJIC), studied here in human fetal skin
      fibroblasts (HFFF2) and in rat liver epithelial cells (WB-F344), was almost
      doubled upon exposure to thalidomide (10 microM) in the presence of NADH or NADPH
      (20 microM). Neither in HFFF2 nor in WB-F344 cells did any detectable alteration
      in GJIC occur with the thalidomide analog EM 16 (10 microM), known as a non
      teratogenic compound. The thalidomide analog EM 364 (10 microM) increased GJIC
      without prior metabolic activation. It is suggested that GJIC modification may be
      related to the pharmacological and toxicological properties of thalidomide.

PMID- 11597577
TI  - Differential regulation of phosphatidylserine externalization and DNA
      fragmentation by caspases in anticancer drug-induced apoptosis of rat mammary
      adenocarcinoma MTLn3 cells.
AB  - Caspase activation is a central event in the execution phase of apoptosis and is
      associated with phosphatidylserine (PS) externalization and DNA fragmentation. We
      investigated the role of caspase activity in anticancer drug-induced PS
      externalization and DNA fragmentation in MTLn3 cells. Caspase activation (DEVD
      AMC cleavage) occurred in a time- and concentration-dependent manner after
      exposure to doxorubicin, in association with cleavage of poly(ADP) ribose
      polymerase and protein kinase C delta, two caspase-3 substrates. Caspase
      activation was closely followed by oligonucleosomal DNA fragmentation and PS
      externalization as determined by flow cytometric analysis. Similar observations
      were made for etoposide and cisplatin. Inhibition of caspases with zVAD-fmk
      inhibited almost completely doxorubicin-induced DNA fragmentation as well as
      proteolysis of protein kinase C delta. In contrast, PS externalization induced by
      doxorubicin was only partly affected by caspase inhibition. Flow cytometric cell
      sorting demonstrated that DNA fragmentation in the remaining PS positive cells
      after doxorubicin treatment in the presence of zVAD-fmk was fully blocked. In
      conclusion, these data indicate that while DNA fragmentation in anticancer drug
      induced apoptosis of MTLn3 cells is fully dependent on caspase activity, PS
      externalization is controlled by both caspase-dependent and caspase-independent
      pathways.

PMID- 11597578
TI  - The cytostatic- and differentiation-inducing effects of cyclopentenyl cytosine on
      neuroblastoma cell lines.
AB  - This paper describes the effects of cyclopentenyl cytosine (CPEC) on the
      proliferation and cell-cycle distribution of the SK-N-BE(2)c and SK-N-SH
      neuroblastoma cell lines, as well as their ability to recover from treatment with
      CPEC. The IC50 value of SK-N-BE(2)c for CPEC, determined after 48 hr was 80 nM.
      SK-N-BE(2)c cells showed a time- and concentration-dependent accumulation in the
      S-phase of the cell cycle after 2 and 3 days of incubation with 50-250 nM CPEC,
      followed by a G0/G1-phase arrest after 4 days. After incubation with 50 nM CPEC
      for 2 days, SK-N-BE(2)c cells fully recovered and resumed logarithmic
      proliferation. In contrast, a complete and persistent growth arrest occurred when
      SK-N-BE(2)c cells were incubated for 2 days with 100 or 250 nM CPEC. The IC50
      value of SK-N-SH, determined after 48 hr, for CPEC was > or =1 microM. SK-N-SH
      cells incubated with 250 nM or 1 microM CPEC showed a time-dependent accumulation
      in the S-phase of the cell cycle, followed by an accumulation in the G0/G1-phase,
      which reached a maximum of 84.1% after 7 days of incubation with 1 microM CPEC.
      SK-N-SH cells did not resume proliferation after removal of the drug. In
      addition, CPEC strongly induced differentiation in SK-N-SH cells. After 48 hr
      incubation with 250 nM CPEC, 90% of the cell population was differentiated. Both
      neuronal type and Schwannian type cells were observed. We conclude that at very
      low concentrations, CPEC has profound cytostatic- and differentiation-inducing
      effects on the neuroblastoma cells studied.

PMID- 11597579
TI  - Stimulation of ERK2 by taurine with enhanced alkaline phosphatase activity and
      collagen synthesis in osteoblast-like UMR-106 cells.
AB  - Taurine is present in a variety of tissues and exhibits many important
      physiological functions in the cell. Even though its functions are well
      documented in many tissues, its actions on bone cells are largely unknown.
      Considering a recent finding that taurine is present in the bone, we wished to
      determine if taurine could have any effects on osteoblast cells. Taurine (10 mM)
      stimulated alkaline phosphatase activity as well as collagen synthesis. Taurine
      also stimulated tyrosine phosphorylation of a number of cellular proteins
      including a 42-kDa protein. The 42-kDa protein was identified as extracellular
      signal regulated protein kinase 2 (ERK2). A mitogen-activated protein kinase
      kinase (MEK) inhibitor blocked the taurine-stimulated alkaline phosphatase
      activity and collagen synthesis. These results suggest that taurine could
      regulate osteoblast metabolism via ERK2 activation.

PMID- 11597580
TI  - Involvement of a post-transcriptional mechanism in the inhibition of CYP1A1
      expression by resveratrol in breast cancer cells.
AB  - Resveratrol decreases basal and induced CYP1A1 mRNA/protein levels in both in
      vitro and in vivo models, and some studies suggest that resveratrol acts as an
      aryl hydrocarbon receptor (AhR) antagonist. Treatment of T47D or MCF-7 cells with
      10 microM resveratrol inhibited induction of CYP1A1 mRNA and CYP1A1-dependent
      activity after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), as
      previously reported. In contrast, resveratrol did not inhibit TCDD-induced
      reporter gene activity in cells transfected with an Ah-responsive construct
      containing a human CYP1A1 gene promoter insert, whereas 3'-methoxy-4'
      nitroflavone, a "pure" AhR antagonist, inhibited this response. Resveratrol
      induced transformation of the rat cytosolic AhR and, after treatment of T47D and
      MCF-7 cells with resveratrol, a transformed nuclear AhR complex was observed. In
      contrast to 3'-methoxy-4'-nitroflavone, resveratrol did not block TCDD-induced
      AhR transformation in vitro or nuclear uptake of the AhR complex in breast cancer
      cells. Thus, the action of resveratrol on the AhR was consistent with that of an
      AhR agonist; however, resveratrol did not exhibit functional AhR agonist or
      antagonist activities in breast cancer cells. Actinomycin D chase experiments in
      T47D cells showed that resveratrol and dehydroepiandrosterone both increased the
      rate of CYP1A1 mRNA degradation, whereas resveratrol did not affect CYP1A1
      dependent activity in cells pretreated with TCDD for 18 hr. These data suggest
      that resveratrol inhibits CYP1A1 via an AhR-independent post-transcriptional
      pathway.

PMID- 11597581
TI  - Participation of Ca2+/calmodulin during activation of rat neutrophils by
      polychlorinated biphenyls.
AB  - The effects of Ca2+ and Ca2+/calmodulin on the polychlorinated biphenyl (PCB)
      induced activation of phospholipase A2 (PLA2) in rat neutrophils were examined.
      The commercial PCB mixture Aroclor 1242 induced activation of PLA2 and promoted
      an increase in the intracellular free calcium concentration ([Ca2+]i). Bromoenol
      lactone (BEL), an inhibitor of the Ca2+-independent PLA2 isoform (iPLA2)
      activated by PCBs, did not abrogate the increase in [Ca2+]i, suggesting that this
      change in Ca2+ concentration is not downstream from the activation of iPLA2. TMB
      8 [8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate], a blocker of the release
      of intracellular Ca2+, decreased Aroclor 1242-induced stimulation of PLA2 with a
      maximal inhibition of 17% at 50 microM. These two results suggest little direct
      dependence between the PCB-induced activation of iPLA2 and increase in [Ca2+]i.
      Calmidazolium and W7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide], two
      chemically distinct calmodulin inhibitors, inhibited Aroclor 1242-induced PLA2
      activity, whereas trifluoperazine (TFP), another inhibitor of calmodulin, had no
      effect at noncytotoxic concentrations. Thus, activation of PLA2 is dependent, in
      part, on calmodulin. Furthermore, both TFP and Aroclor 1242 inhibited neutrophil
      degranulation stimulated by the bacterial peptide formyl-methionyl-leucyl
      phenylalanine. These results raise the possibility that some of the effects of
      PCBs on neutrophil function can be explained by effects on Ca2+/calmodulin
      dependent processes.

PMID- 11597582
TI  - Further evidence for the involvement of inhibition of cell proliferation and
      development in thymic and splenic atrophy induced by the peroxisome proliferator
      perfluoroctanoic acid in mice.
AB  - We recently demonstrated that severe thymic and splenic atrophy occur upon
      dietary treatment of mice with potent peroxisome proliferators (PPs), e.g.
      perfluorooctanoic acid (PFOA), WY-14,643, nafenopin, and di(2
      ethylhexyl)phthalate (DEHP). In the present study, we investigated this
      phenomenon further employing a relative inert PP, PFOA. Comparison of the dose
      dependencies and time-courses indicated that the peroxisome proliferative effect
      occurred prior to atrophy of both the thymus and spleen. However, following
      withdrawal of PFOA from the diet, the weight of the thymus and spleen rapidly
      returned to normal within 10 and 5 days, respectively, in contrast to the more
      persistent peroxisome proliferation. Furthermore, the changes in thymus and
      spleen weight upon PFOA treatment and the following withdrawal from diet
      paralleled the changes in total thymocyte and splenocyte counts, respectively. It
      was found previously that the decreases in the thymocyte populations present in
      the S and G2/M phases, as well as in the number of CD4+CD8+ cells upon PFOA
      treatment, were the most dramatic, perhaps reflecting inhibition of thymocyte
      proliferation in connection with thymocyte development. Here, the recovery of
      thymocytes began with increases in the populations in these same phases of the
      cell cycle, with CD4+CD8+ cells recovering most rapidly, lending further support
      to our previous hypothesis. The possible relationship of these immunotoxic
      effects of PPs to the changes they cause in fatty acid metabolism is discussed.

PMID- 11597583
TI  - Role of tumor necrosis factor-alpha in endotoxin-induced lung parenchymal
      hyporesponsiveness in mice.
AB  - Although changes in airway responsiveness in pulmonary inflammation are commonly
      related to the action of infiltrated leukocytes, our previous report suggested a
      direct role of inflammatory cytokines in LPS-induced lung hyporesponsiveness. The
      aim of this study was to define if cytokines detected in the BALF
      (bronchoalveolar lavage fluid) of intratracheal LPS-treated mice could be, at
      least in part, responsible for 5-HT (5-hydroxytryptamine) lung hyporeactivity.
      Our results show that intratracheal instillation of LPS induced a time-dependent
      increase in IL-(interleukin-)1beta, IL-6, and TNF (tumor necrosis factor)alpha in
      the BALF. Cytokine production was paralleled by 5-HT lung hyporesponsiveness, and
      intratracheal administration of TNFalpha proved to be very efficient in
      inhibiting 5-HT responsiveness. In addition, systemic treatment with rolipram, an
      inhibitor of TNFalpha production, was paralleled by a significant recovery of
      lung responsiveness. On the contrary, IL-1beta and IL-6 were not demonstrated to
      play a relevant role in 5-HT hyporesponsiveness. It is concluded that TNFalpha
      could be a crucial mediator of LPS-induced lung hyporesponsiveness.

PMID- 11597584
TI  - The impact of different flavonoid classes on colonic CI- secretion in rats.
AB  - The plant polyphenol quercetin was shown to induce a significant CI- secretion in
      intestinal epithelium. In order to elucidate the structural requirements of
      quercetin and related flavonoids for this activity, we tested the ability of
      further flavonols and other flavonoids found in edible plants to induce CI-
      secretion which was measured as an increase in short-circuit current (I(SC)) in
      rat colon. Whereas several flavonols and the flavon luteolin increased I(SC),
      other flavonoids such as flavanones, flavans, flavanols, and anthocyanidins
      failed to do so. Two glycosides of quercetin, spiraeosid, and isoquercitrin, as
      well as two methoxylated quercetin metabolites, isorhamnetin and tamarixetin,
      were also able to increase I(SC). We conclude that a 2,3-double bond in
      conjunction with the 4-oxo group in the C ring and a hydroxylated B ring are
      necessary for the secretory activity of flavonoids. This activity requires
      different structural features than those mandatory for the antioxidative
      properties of flavonoids. Glucosidation and methoxylation of several hydroxyl
      groups does not necessarily abolish the secretory potential.

PMID- 11597585
TI  - A novel protein interacts with a clock-related protein, rPer1.
AB  - Mammalian Per proteins are thought to be important in the mechanism of circadian
      rhythm. We identified a novel protein PIPS (Per1 interacting protein of the
      suprachiasmatic nucleus) with the yeast two-hybrid system using PAS domain of rat
      Per1 (rPer1) as a bait. PIPS is about a 180-kDa protein and expressed mainly in
      the brain, especially in the hypothalamus including the suprachiasmatic nuclei
      (SCN). PIPS interacts with mouse Per1 (mPer1) in vitro and in cultured cells
      transfected with both molecules. Furthermore, it was found that mPer1
      translocated PIPS into the nuclei in the cultured cells. Thus, these findings
      suggest a possibility that PIPS is involved in the feedback loop or output
      mechanism of circadian rhythm through interacting with Per1 in the SCN.

PMID- 11597586
TI  - C-FOS expression in the rat brain in response to substance P and neurokinin B.
AB  - Substance P, the principal neurokinin peptide in the mammalian brain and the
      natural ligand for the NK(1) tachykinin receptor, plays an integrative role in
      the regulation of cardiovascular, neuroendocrine and behavioural responses to
      stress. In rats, stimulation of periventricular NK(1) receptors in the forebrain
      induces a distinct pattern of cardiovascular responses which is accompanied by
      intense grooming behaviour. Ligands for NK(3) receptors induce a different
      pattern of cardiovascular and behavioural responses which comprises an increased
      release of vasopressin from the posterior pituitary and wet-dog shakes behaviour.
      To define the brain areas in the rat which respond to stimulation of forebrain
      NK(1) and NK(3) receptors and participate in the generation of these responses,
      the induction of c-Fos immunoreactivity was examined in brains following
      intracerebroventricular injections of substance P and neurokinin B in conscious
      rats. Stimulation of central NK(1) receptors by substance P (25, 100 and 500
      pmol) injected into the lateral ventricle elicited grooming behaviour (face
      washing and hind limb grooming) and resulted in a marked c-Fos expression in the
      paraventricular, dorsomedial and parabrachial nuclei and in the medial thalamus.
      At 25 pmol, substance P did not significantly increase c-Fos expression, at 100
      pmol, maximal c-Fos activation was induced in all four brain regions which
      responded to the peptide. Intracerebroventricular pretreatment of rats with the
      selective and high-affinity, non-peptide NK(1) receptor antagonist, RP 67580 (500
      pmol), but not with its inactive enantiomer, RP 68651, completely abolished the
      behavioural response to substance P and reduced the substance P-induced c-Fos
      expression in all brain areas to nearly control levels. Intracerebroventricular
      injection of the natural ligand for NK(3) receptors, neurokinin B (500 pmol),
      elicited wet-dog shakes behaviour and activated c-Fos expression in localized
      regions of the forebrain including the organum vasculosum laminae terminalis,
      subfornical organ, median preoptic nucleus, paraventricular, supraoptic and
      anterior hypothalamic nuclei, medial thalamus and in the ventral tegmental area.
      These results demonstrate that the neurokinins, substance P and neurokinin B,
      induce specific and different patterns of c-Fos expression in distinct regions of
      the rat brain. Brain areas which selectively responded to substance P have been
      traditionally linked to the central regulation of cardiovascular and
      neuroendocrine reactions to stress or involved in the processing of nociceptive
      responses. On the other side, brain areas activated by neurokinin B are known to
      be involved in the central regulation of blood pressure, water and salt
      homeostasis or control of behaviour.

PMID- 11597587
TI  - Age-related changes in muscarinic cholinergic receptors in the living brain: a
      PET study using N-[11C]methyl-4-piperidyl benzilate combined with cerebral blood
      flow measurement in conscious monkeys.
AB  - The effects of changes in regional cerebral blood flow (rCBF) with aging on
      muscarinic cholinergic receptor binding were evaluated with [15O]H(2)O and N
      [11C]methyl-4-piperidyl benzilate (4-MPB) in the living brains of young (5.9+/
      1.8 years old) and aged (19.0+/-3.3 years old) monkeys (Macaca mulatta) in the
      conscious state using high-resolution positron emission tomography (PET). For
      quantitative analysis of receptor binding in vivo with [11C]4-MPB, metabolite
      corrected arterial plasma radioactivity curves were obtained as an input function
      into the brain, and graphical Patlak plot analysis was applied. In addition, two
      compartment model analysis using the radioactivity curve in the cerebellum as an
      input function (reference analysis) was also applied to determine the
      distribution volume (DV=K(1)/k(2)') for [11C]4-MPB. With metabolite-corrected
      arterial input, Patlak plot analysis of [11C]4-MPB indicated a regionally
      specific decrease in muscarinic cholinergic receptor binding in vivo in the
      frontal and temporal cortices as well as the striatum in aged compared with young
      animals, showing no correlation with the degree of reduced rCBF. In contrast, on
      the reference analysis with cerebellar input of [11C]4-MPB, all regions assayed
      except the pons showed a significant age-related decrease of DV, and the degree
      of reduction of DV was correlated with that of rCBF. These results demonstrated
      the usefulness of kinetic analysis of [11C]4-MPB with metabolite-corrected
      arterial input, not with reference region's input, as an indicator of the aging
      process of cortical muscarinic cholinergic receptors in vivo measured by PET with
      less blood flow dependency.

PMID- 11597588
TI  - Ryanodine receptor-mediated [Ca(2+)](i) release in glomus cells is independent of
      natural stimuli and does not participate in the chemosensory responses of the rat
      carotid body.
AB  - The hypothesis that intracellular calcium ([Ca(2+)](i)) release in glomus cells
      via ryanodine receptor (RyR) activation by caffeine may be independent of natural
      stimuli and chemosensory discharge was tested in the rat carotid body (CB). CB
      type I cells were isolated, plated and preloaded with calcium-sensitive
      fluorescent probe, Indo-1AM. With the increase of caffeine dose (0-50 mM)
      cytosolic calcium ([Ca(2+)](c)) increased from 85+/-15 nM to 1933+/-190 nM (n=6)
      at normoxia (PO(2)=125-130 Torr, PCO(2)=25-30 Torr, pH 7.30-7.35). Hypoxia
      (PO(2)=10-15 Torr) increased and hypocapnia (PCO(2)=7-9 Torr) decreased the
      cytoplasmic calcium [Ca(2+)](c) levels, independent of caffeine. Caffeine-related
      [Ca(2+)](c) increase was the same in the presence and the absence of
      extracellular calcium ([Ca(2+)](o)), indicating the source of Ca(2+) ions is the
      cellular store. Permeabilization of the cell membrane with saponin (25 microg/ml)
      retained the caffeine response. Additional treatment of the cells with 50 microM
      ryanodine (an inhibitor of the caffeine-activated RyR site) abolished caffeine
      stimulated response. In vitro CB chemosensory (carotid sinus nerve, CSN)
      responses to hypoxia (PO(2)=35-40 Torr) were not altered by caffeine. These
      results suggest that [Ca(2+)](i) stores in CB cells, mobilized by RyR activation,
      do not participate in the CSN responses to natural stimuli.

PMID- 11597589
TI  - Prostanoids in the preoptic hypothalamus mediate systemic lipopolysaccharide
      induced hyperalgesia in rats.
AB  - The systemic administration of lipopolysaccharide (LPS), an experimental model of
      systemic bacterial infection is known to modulate nociception. It increases the
      prostaglandin E(2) (PGE(2)) levels in the preoptic area of the hypothalamus (POA)
      and the microinjection of PGE(2) into the POA and the neighboring basal forebrain
      induces hyperalgesia. We, therefore, hypothesized that the PGE(2) synthesized in
      these regions mediates intravenous (i.v.) LPS-induced hyperalgesia. To test this
      hypothesis, we microinjected cyclooxygenase (COX) inhibitors into several sites
      in the rat hypothalamus and observed their effects on the LPS (0.1-100 microg/kg,
      i.v.)-induced changes in nociceptive behavior as assessed by a plantar test. LPS
      (10 and 100 microg/kg, i.v.) reduced the paw-withdrawal latency at 90 min and 45
      60 min after injection, respectively, both thus indicating a hyperalgesic effect.
      This hyperalgesia was observed only in the period before the development of fever
      which started 120-135 min after the LPS injection. The LPS (100 microg/kg, i.v.)
      induced hyperalgesia was completely abolished by pretreatment with the
      microinjection of diclofenac (an inhibitor of COX-1 and 2) at 1.0 ng into the
      bilateral POA. Furthermore, it was also blocked by the microinjection of NS-398
      (a selective COX-2 inhibitor) at 1.0 ng into the bilateral POA and the horizontal
      limb of the diagonal band of Broca (DBB), but not the lateral hypothalamic area,
      the paraventricular hypothalamic nucleus, and the ventromedial hypothalamic
      nucleus. These findings suggest that LPS (i.v.)-induced hyperalgesia is mediated
      predominantly through a COX-2 induced prostanoids in the POA and the DBB in rats.

PMID- 11597590
TI  - Acidic regulation of junction channels between glomus cells in the rat carotid
      body. Possible role of [Ca(2+)](i).
AB  - The purpose of this work was to characterize the gap junctions between cultured
      glomus cells of the rat carotid body and to assess the effects of acidity and
      accompanying changes in [Ca(2+)](i) on electric coupling. Dual voltage clamping
      of coupled glomus cells showed a mean macrojunctional conductance (G(j)) of 1.16
      nS+/-0.6 (S.E.), range 0.15-4.86 nS. At normal pH(o) (7.43), a steady
      transjunctional voltage (DeltaV(j)=100.1+/-10.9 mV) showed multiple junction
      channel activity with a mean microconductance (g(j)) of 93.98+/-0.6 pS, range 0.3
      324.5 pS. Single-channel conductances, calculated as variance/mean g(j), gave a
      mean value of 16.7+/-0.2 pS, range 5.13-39.38 pS. Manual measurements of single
      channel activity showed a mean g(j) of 22.03+/-0.2 pS, range 1.3-160 pS. Computer
      analysis of the noise spectral density distribution gave a channel mean open time
      of 12.7+/-1.5 ms, range 6.37-23.42 ms. The number of junction channels, estimated
      in each experiment from G(j)/single-channel g(j), showed a range of 7 to 258
      channels (mean, 107.2). Optical measurements of [Ca(2+)](i) gave a mean value of
      80.2+/-4.27 nM at pH(o) of 7.43. Acidification of the medium with lactic acid (1
      mM, pH 6.3) induced: 1) Variable changes in G(j) (decreases and increases); 2) A
      significant decrease in mean g(j) (to 80.36+/-0.34 pS) and in single-channel
      conductance (g(j)=12.8+/-0.2 pS in computer analyses and 17.23+/-0.2 pS when
      measured by hand); 3) Variable changes in open times, resulting in a similar mean
      (12.8+/-1.5 ms) and 4) No change in the number of junction channels. When pH(o)
      was lowered to 6.3 [Ca(2+)](i) did not change significantly (there were increases
      and decreases). However, when pH(o) was lowered to 4.4, [Ca(2+)](i) increased
      significantly to 157.1+/-8.1 nM. It is concluded that saline acidification to pH
      6.3 depresses the conductance of junction channels and this effect may be either
      a direct effect on channel proteins or synergistically enhanced by increases in
      [Ca(2+)](i). However, there are no studies correlating changes of [Ca(2+)](i) and
      intercellular coupling in glomus cells. Stronger acidification (pH(o) 4.4),
      producing much larger changes in [Ca(2+)](i), may enhance this synergism. But,
      again, there are no studies correlating these effects.

PMID- 11597591
TI  - Antagonizing effect of protein kinase C activation on the mu-opioid agonist
      induced inhibition of high voltage-activated calcium current in rat
      periaqueductal gray neuron.
AB  - Opioids have been thought to induce analgesia by activating the descending pain
      control system, especially at the level of periaqueductal gray, and regulate the
      neurotransmitter release through the inhibition of calcium channel. In the
      present study, the modulatory effects of protein kinase C and protein kinase A on
      the mu-opioid agonist-induced inhibition of the high-voltage activated calcium
      current were examined in the acutely dissociated rat periaqueductal gray neurons
      with the nystatin-perforated patch-clamp technique. Among 505 neurons tested, the
      barium current passing through the high-voltage activated calcium channels of 172
      neurons (34%) were inhibited by 32+/-3% with the application of an mu-opioid
      agonist, [D-Ala(2),N-MePhe(4),Gly(5)-ol]-enkephalin (DAMGO, 1 microM). The barium
      currents itself and the DAMGO-induced inhibitory effects were not affected by the
      application of either an adenylate cyclase activator (forskolin, 1 microM) or a
      protein kinase inhibitor (staurosporin, 10 nM) for 2 min. The DAMGO inhibition
      was completely and irreversibly antagonized by the application of a protein
      kinase C activator, phorbol-12-myristate-13-acetate (PMA, 1 microM) for 2 min
      without any alteration of the barium current itself. However, the antagonizing
      effect of PMA was completely abolished by the application of 10 nM staurosporin
      for 2 min. After then, PMA did not show the antagonizing effect any more.
      Inversely, when staurosporin was applied before PMA, the antagonizing effect of
      PMA was also not shown. These results demonstrate that the mu-opioid agonist
      induced inhibition of the periaqueductal gray neuronal high-voltage activated
      calcium current can be antagonized by protein kinase C activation. This finding
      may provide us a significant clue to understand the action mechanism of opioid
      induced analgesia in the periaqueductal gray.

PMID- 11597592
TI  - Intrastriatal administration of 3-hydroxyglutaric acid induces convulsions and
      striatal lesions in rats.
AB  - Glutaryl-CoA dehydrogenase deficiency is an inherited neurometabolic disease
      complicated by precipitation of acute encephalopathic crises during a vulnerable
      period of brain development. These crises result in bilateral striatal damage and
      subsequently a dystonic dyskinetic movement disorder. In previous in vitro
      studies neuronal damage in this disease has been linked to an excitotoxic
      mechanism mediated in particular by one of the accumulating metabolites, 3
      hydroxyglutaric acid. However, nothing is known about the in vivo effects of this
      organic acid. In the present study, we used a stereotaxic intrastriatal injection
      technique to investigate the behavioral and neurotoxic effects of 3
      hydroxyglutaric acid exposure in rats. Here, we report that 3-hydroxyglutaric
      acid induced an increase in convulsion frequency and duration as determined by
      open field measurement. Nissl-stained coronal sections from treated rats revealed
      a pale lesion in the striatum following 3-hydroxyglutaric acid exposure. N-methyl
      D-aspartate (NMDA) receptor blockade by MK-801 and stimulation of GABA(A)
      receptors by muscimol prevented the induction of convulsions and striatal damage
      by 3-hydroxyglutaric acid, whereas blockade of non-NMDA receptors by 6,7
      dinitroquinoxaline-2,3-dione (DNQX) was not protective. We conclude that 3
      hydroxyglutaric acid induces convulsions and striatal damage via initiation of an
      imbalance in the excitatory glutamatergic and the inhibitory GABAergic
      neurotransmission, resulting in an enhanced excitatory input in striatal neurons.
      These results support the hypothesis of NMDA receptor-mediated excitotoxic cell
      damage in glutaryl-CoA dehydrogenase deficiency and represent the basis for the
      development of new neuroprotective treatment strategies.

PMID- 11597593
TI  - GDNF is a major component of trophic activity in DA-depleted striatum for
      survival and neurite extension of DAergic neurons.
AB  - Extracts from dopamine (DA)-depleted striatal tissue (lesion extract) and from
      intact striatal tissue (intact extract) were prepared, and trophic activities in
      these extracts were evaluated using survival and neurite extension of DAergic
      neurons as indices. Levels of brain-derived neurotrophic factor (BDNF), basic
      fibroblast growth factor (bFGF), glial cell-line derived neurotrophic factor
      (GDNF) and neurotrophin-3 (NT-3) in extracts were measured using enzyme-linked
      immunosorbent assay (ELISA). The lesion extract exhibited a stronger trophic
      activity on survival and neurite extension of DAergic neurons than intact
      extract. In lesion extract, bFGF was slightly and GDNF was significantly
      increased, while BDNF and NT-3 were the same level in each extract. The peak
      increase of bFGF and GDNF was during 2 to 3 weeks after DA depletion. Trophic
      activity of extract was strongly attenuated after immunoprecipitation of GDNF and
      partly attenuated after immunoprecipitation of bFGF. In parallel
      immunohistological study, no significant variations were found for striatal
      microtubule-associated protein-2 (MAP-2)- nor OX-41-immunoreactive cells, while
      the number of strongly labeled glial fibrillary acidic protein (GFAP)
      immunoreactive cells were increased in DA-depleted striatum, suggesting reactive
      gliosis. Data suggest that bFGF is a minor, while GDNF is a major component of
      trophic activity for DAergic neurons in DA-depleted striatum, and increased bFGF
      and GDNF levels may be mediated partly by reactive gliosis.

PMID- 11597594
TI  - Effect of hyperbaric oxygen on striatal metabolites: a microdialysis study in
      awake freely moving rats after MCA occlusion.
AB  - We have shown that hyperbaric oxygen (HBO) reduced cerebral infarction in rat
      middle cerebral artery occlusion model (MCAO). The present study was undertaken
      to evaluate the effect of HBO on ischemic striatal metabolites at different times
      after MCAO and reperfusion. A rat MCAO model was produced via the intraluminal
      filament method. After 2 h of occlusion the suture was removed and reperfusion
      was allowed. The rats were sacrificed at 24 h after reperfusion. HBO treatment
      was administered by putting rats in the HBO chamber at 3 atmospheres absolute
      (ATA) HBO for 1 h. Glucose, lactate, pyruvate, and glutamate in striatal
      extracellular fluid were collected and measured by a microdialysis system at 7,
      10, and 24 h after reperfusion. Glucose, pyruvate and glutamate concentrations
      were increased after reperfusion. HBO treatment decreased glucose, pyruvate, and
      glutamate almost to the control level (preocclusion level). The lactate
      concentration remained unchanged after ischemic/reperfusion and after HBO
      treatment. This study suggested that altered brain energy metabolites and
      excitatory amino acids occurred during cerebral ischemia and and HBO regulated
      these striatal metabolites, which might contribute to the protective effect of
      HBO in cerebral ischemia.

PMID- 11597595
TI  - Effects of psychological stress on monoamine systems in subregions of the frontal
      cortex and nucleus accumbens of the rat.
AB  - We investigated the effects of two types of psychological stress, novelty stress
      and psychological stress using the communication box, on dopamine and serotonin
      systems in subregions of the frontal cortex and nucleus accumbens of rats.
      Placement of rats into a compartment of the communication box (novelty stress)
      increased both dopamine and serotonin metabolism in medial precentral, anterior
      cingulate, and prelimbic subregions of the frontal cortex as evaluated by the
      levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid for dopamine, and
      5-hydroxyindoleacetic acid for serotonin. In contrast, novelty stress had no
      effect on these monoamine systems in infralimbic and sulcal subregions of the
      frontal cortex. In the nucleus accumbens, novelty stress increased both dopamine
      and serotonin metabolism in the shell, but decreased dopamine metabolism in the
      core. On the other hand, psychological stress using the communication box
      augmented dopamine metabolism in the anterior cingulate and prelimbic subregions.
      This stress, however, failed to affect the dopamine system in the medial
      precentral, infralimbic and sulcal subregions. In the nucleus accumbens, the
      stress selectively decreased dopamine metabolism in the shell but showed no
      effect in the core. The serotonin system showed little change due to the stress.
      These results demonstrate that psychological stress causes distinct changes in
      both the dopamine and serotonin systems in the frontal cortex and the nucleus
      accumbens. These changes vary with the subregions of these areas, suggesting that
      the region-specific responsiveness to psychological stress reflects the
      functional differences among these subregions. In addition, our results also
      suggest that changes in brain monoamine systems induced by psychological stress
      are quite different from those induced by physical stress.

PMID- 11597596
TI  - Involvement of the bed nucleus of the stria terminalis in hippocampal cholinergic
      system-mediated activation of the hypothalamo--pituitary--adrenocortical axis in
      rats.
AB  - This study was designed to determine the effect of the bed nucleus of the stria
      terminalis (BNST) in hippocampal cholinergic system-mediated activation of the
      hypothalamo--pituitary--adrenocortical (HPA) axis in the rat. Neurons in the BNST
      were lesioned by bilateral injection of the cell-selective neurotoxin, ibotenic
      acid (1.5 microg/microl of solution per side). Two weeks later, neostigmine was
      microinjected into the rats' hippocampus. Rats in which ibotenic acid had been
      injected into the BNST showed attenuated expression of c-Fos in the hypothalamic
      paraventricular nucleus (PVN) and blunted elevation of plasma adrenocorticotropic
      hormone (ACTH) after microinjection of neostigmine into the hippocampus compared
      with rats in which saline had been injected into the BNST. The results of this
      study indicate that the BNST relays signals of hippocampal cholinergic system
      mediated activation of the HPA axis in rats.

PMID- 11597597
TI  - Detection of pharmacologically mediated changes in cerebral activity by
      functional magnetic resonance imaging: the effects of sulpiride in the brain of
      the anaesthetised rat.
AB  - Blood oxygenation level dependent (BOLD) contrast functional magnetic resonance
      imaging (fMRI) was used to study the effects of the D(2)-like receptor selective
      antagonist, sulpiride, at 2 Tesla in the brain of the alpha-chloralose
      anaesthetised rat. Region of interest (ROI) analysis indicated significant
      (P<0.05) bilateral increases in BOLD signal intensity in the frontal cortex
      following a single administration of sulpiride (10 mg/kg i.v.). BOLD signal
      changes were slow in onset and increased gradually during the experiment,
      reaching 8.0+/-0.5% (mean+/-S.E.M.) above pre-injection control values 165 min
      after drug administration. Signal increases remained high at the experiment end
      (3 h post sulpiride administration). Sulpiride (30 mg/kg i.v.) had a similar
      effect in the frontal cortex, increasing signal 5.2+/-1.8% above control values
      by 174 min; its effects were, however, more variable between rats, and were not
      statistically significant. Sulpiride (3 mg/kg i.v.) had no significant effect
      upon BOLD signal intensity in any brain region. No dose of sulpiride resulted in
      any significant BOLD signal changes in the striatum or cerebellum. These data are
      supportive of the notion that sulpiride causes an increase in frontal
      dopaminergic function by antagonism of presynaptically located dopamine D(2)
      receptors in this brain region, consistent with its therapeutic action.
      Furthermore, the utility of BOLD contrast fMRI as a means of detecting changes in
      neuronal activity contingent upon the administration of a psychoactive
      pharmacological agent has been demonstrated.

PMID- 11597598
TI  - Inhibition of calpain-mediated apoptosis by E-64 d-reduced immediate early gene
      (IEG) expression and reactive astrogliosis in the lesion and penumbra following
      spinal cord injury in rats.
AB  - Upregulation of calpain, a Ca(2+)-activated cysteine protease, has been
      implicated in apoptosis and tissue degeneration in spinal cord injury (SCI) that
      over time spreads from the site of injury to the surrounding regions. We examined
      calpain content and activity, regulation of immediate early genes (IEGs) such as
      c-jun and c-fos, reactive astrogliosis as the expression of glial fibrillary
      acidic protein (GFAP), and apoptosis-related features such as caspase-3 mRNA
      expression and internucleosomal DNA fragmentation in 1-cm long spinal cord
      segments (S1, distant rostral; S2, adjacent rostral; S3, lesion or injury; S4,
      adjacent caudal; and S5, distant caudal) following SCI in rats. Calpain content
      and production of 150 kD calpain-cleaved alpha-fodrin fragment, expression of
      IEGs, reactive astrogliosis, and apoptotic features were highly increased in the
      lesion (S3), moderately in adjacent areas (S2 and S4), and slightly in distant
      areas (S1 and S5) in SCI rats when compared to sham animals. Administration of
      the calpain-specific inhibitor E-64-d (1 mg/kg) to SCI rats continuously for 24 h
      inhibited calpain activity and other factors contributing to apoptosis in the
      lesion and surrounding areas, indicating that calpain played a key role in the
      pathophysiology of SCI. The results obtained from this animal model of SCI
      suggest that calpain inhibitor can provide neuroprotection in patients with SCI.

PMID- 11597599
TI  - Interactions among ascorbate, dehydroascorbate and glucose transport in cultured
      hippocampal neurons and glia.
AB  - There is an increasing recognition of the damaging role played by oxygen radicals
      in mediating necrotic neuronal injury. As such, it becomes important to
      understand the transport mechanisms that help maintain appropriate levels of
      small molecule antioxidants such as ascorbate in the brain. It has long been
      known that the transport of dehydroascorbate (DHA) into a variety of cell types
      is accomplished through the Glut-1 glucose transporter. In this paper, we
      characterize interactions among the transports of ascorbate, DHA and glucose in
      hippocampal cultures. We find: (a) sodium-dependent transport of ascorbate in
      mixed neuronal/glial, pure glial, and neuron-enriched hippocampal cultures; in
      contrast, we observed no such transport of DHA; (b) such ascorbate transport
      appeared to be independent of the glucose transporter, in that glucose did not
      compete for such transport, and overexpression of the Glut-1 glucose transporter
      did not alter ascorbate uptake; (c) in contrast, ascorbate, at concentrations
      ranging from 1 to 20 mM inhibited 2-dexogyglucose transport in mixed, glial and
      enriched neuronal hippocampal cultures; (d) potentially, ascorbate, by acting as
      an electron donor, could impair the function of molecules involve in the
      transport or metabolism of glucose. We observed mild inhibition of glucose
      transport by one unrelated electron donor (glutathione). Moreover, transport was
      also inhibited by an ascorbate analog which is not an electron donor. Thus, we
      conclude that ascorbate transport in hippocampal neurons and glia occurs
      independent of the glucose transporter but that, nevertheless, ascorbate, at
      concentrations generally thought to be supraphysiological, has the potential for
      disrupting glucose transport.

PMID- 11597600
TI  - Endogenous CRX expression and IRBP promoter activity in retinoblastoma cells.
AB  - PURPOSE: To determine whether antisense oligonucleotides (AODNs) targeted against
      CRX, a photoreceptor-specific trans-acting factor, suppress CRX expression and
      interphotoreceptor retinoid binding protein (IRBP) promoter activity. METHODS:
      Cultures of human retinoblastoma cells were transfected with chloramphenicol
      acetyltransferase (CAT) reporter plasmids containing a mouse IRBP promoter and
      AODNs directed against CRX. RT-PCR using primers specific to CRX, OTX2, GAPDH, or
      RNase H was conducted on total RNA isolated from retinoblastoma cells at various
      times following transfection with AODNs. RESULTS: Transfection of retinoblastoma
      cells with IRBP promoter CAT constructs alone produced high activity. Co
      transfection with AODNs suppressed IRBP promoter activity in a concentration
      dependent manner, with half-maximal effect produced at about 2 nM AODN
      concentration. Transfection with CAT constructs containing an SV40 promoter
      produced high activity that was unaffected by co-transfection with AODNs. RT-PCR
      products were obtained for all target sequences. CRX RT-PCR product from cells
      transfected with AODNs was greatly diminished following transfection with an AODN
      whereas control transcripts, including that of OTX2, were relatively unaffected.
      CONCLUSIONS: The CRX-specific AODNs specifically and potently suppressed CRX
      expression and IRBP promoter activity, as measured by RT-PCR and transient
      transfection assays, respectively. Little or no effect was seen on controls.
      These data suggest that endogenous CRX is required for IRBP promoter activity in
      retinoblastoma cells.

PMID- 11597601
TI  - Altered responsiveness to 5-HT at the crayfish neuromuscular junction due to
      chronic p-CPA and m-CPP treatment.
AB  - Serotonin (5-HT) levels in the hemolymph of crustaceans has been implied to alter
      aggressiveness which influences social interactions. The activation of IP3 as a
      second messenger cascade within crayfish motor neurons in response to application
      of 5-HT, suggests that the 5-HT receptor subtypes on the motor neurons are
      analogous to the vertebrate 5-HT2A receptors. Based on evidence in other systems,
      it would be expected that chronically sustained 5-HT levels in aggressive
      individuals would result in a compensatory negative feed-back regulation and/or
      that target tissues would diminish their sensitivity to high levels of
      circulating, free 5-HT. We addressed the issue of up- and down-regulation in the
      sensitivity of the responsiveness to exogenously applied 5-HT at the NMJs of
      crayfish in which the animals have altered endogenous 5-HT levels. Injections of
      the 5-HT1 and 5-HT2 vertebrate receptor agonist, 1-(3-Chlorophenyl) piperazine
      dihydrochloride (m-CPP), for 1 week resulted in a decreased responsiveness to
      application of 5-HT. The compound p-chlorophenylalanine (p-CPA) blocks the
      enzymatic synthesis of 5-HT and following 7 days of p-CPA injections, a super
      sensitivity to exogenous application of 5-HT for both tonic and phasic
      neuromuscular junctions (NMJs) was observed. However, acute applications of p-CPA
      and m-CPP, followed by extensive saline washing, did not reveal any altered
      receptivity to 5-HT application.

PMID- 11597602
TI  - Increased glutamate, GABA and glutamine in lateral geniculate nucleus but not in
      medial geniculate nucleus caused by visual attention to novelty.
AB  - This study is concerned with cortico-thalamic neural mechanisms underlying
      attentional phenomena. Previous results from this laboratory demonstrated that
      the visual sector of the GABAergic thalamic reticular nucleus is selectively c
      fos activated in rats that are naturally paying attention to features of a novel
      complex environment, and that this activation is dependent on top-down
      glutamatergic inputs from the primary visual cortex. By contrast, the acoustic
      sector of the thalamic reticular nucleus is not activated despite noise generated
      by exploration and c-fos activation of brainstem acoustic centers (e.g. dorsal
      cochlear nucleus, inferior colliculus). A prediction of these results is that the
      levels of the neurotransmitters glutamate and GABA, and the glutamate-related
      amino acid glutamine, will be increased in the lateral geniculate nucleus (LGN),
      but not in the medial geniculate nucleus (MGN) of rats that explore a novel
      complex environment in comparison to levels of these amino acids in control rats.
      By means of neurochemical analysis of these amino acids (HPLC) the results of
      this study confirmed this prediction. The results are consistent with the
      previously proposed 'focal attention' hypothesis postulating that a focus of
      attention in the primary visual cortex generates top-down center-surround
      facilitatory-inhibitory effects on geniculocortical transmission via
      corticoreticulogeniculate pathways. The results also supports the notion that a
      main function of corticothalamic pathways to relay thalamic nuclei is attention
      dependent modulation of thalamocortical transmission.

PMID- 11597603
TI  - Concentration-dependent effects of the esterase inhibitor BNPP on macrophage
      migration and myelin phagocytosis.
AB  - Wallerian degeneration of a peripheral nerve is mainly characterized by axon and
      myelin degradation and is paralleled by a massive invasion of peripheral
      macrophages into the nerve. These cells enter the nerve attracted by a cascade of
      chemokines and cytokines but require proteolytic and enzymatic factors which
      enables them to cross the blood-nerve barrier. Here we investigated whether alpha
      naphthyl (alpha-NA) esterases -- which have been shown to be exclusively
      expressed in human monocytes -- play a role during Wallerian degeneration. These
      enzymes were blocked by the specific inhibitor bis(4-nitrophenyl)-phosphate
      (BNPP) in an established in vitro model of Wallerian degeneration. Sciatic nerve
      segments of mice were co-cultured with peritoneal macrophages and BNPP was added
      to the cultures in various concentrations and at different timepoints. The
      macrophage numbers and myelin density in the nerve segments and the myelin load
      of macrophages were evaluated. After BNPP treatment the macrophage number within
      the nerve was significantly diminished and the myelin load within the macrophages
      was decreased, resulting in elevated levels of preserved myelin within the
      nerves. These experiments clearly showed a double effect of the alphaNA esterase
      inhibitor BNPP on macrophages. First, it suggests a role for alphaNA esterases on
      the migratory potential of macrophages since their invasion into the nerves was
      diminished. Second, the reduced myelin uptake is due to the inhibition of
      phagocytic capacity of these cells by BNPP. The therapeutical use of this
      inhibitor for treatment of autoimmune diseases such as multiple sclerosis or
      Guillain-Barre syndrome remains to be investigated.

PMID- 11597604
TI  - Receptor reserve of phosphoinositide-coupled muscarinic receptors in mouse
      hippocampus in vivo.
AB  - The ability of the partial muscarinic agonist pilocarpine to increase in vivo
      phosphoinositide (PI) hydrolysis in mouse brain was compared to two full
      agonists. Pilocarpine increased in vivo phosphoinositide (PI) hydrolysis in
      cortex, striatum, and to the greatest extent in the hippocampus. Pilocarpine
      injected either subcutaneously or intracerebroventricularly robustly increased in
      vivo PI hydrolysis in hippocampus up to 500% of control levels and the increases
      were blocked by the muscarinic antagonist scopolamine. The increases in vivo PI
      hydrolysis induced by pilocarpine were 60-75% of the magnitude of the full
      muscarinic agonists oxotremorine-M and cis-dioxolane. The muscarinic M(1)
      preferring antagonist pirenzepine potently blocked pilocarpine-induced increases
      in in vivo PI hydrolysis, consistent with the increase being mediated by M(1)
      receptors. Since pilocarpine is a relatively weak partial agonist, these data
      suggest a substantial level of receptor reserve for the PI response in mouse
      hippocampus.

PMID- 11597605
TI  - Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization
      and efferent projections.
AB  - The suprachiasmatic nucleus (SCN) is the principal circadian pacemaker of the
      mammalian circadian timing system. The SCN is composed of two anatomically and
      functionally distinct subdivisions, designated core and shell, which can be
      distinguished on the basis of their chemoarchitecture and connections in the rat.
      In the present study, we examine the intrinsic organization and the afferent and
      efferent connections of the mouse SCN using immunocytochemistry and ocular
      injections of cholera toxin. Neurons of the SCN shell contain GABA, calbindin
      (CALB), arginine vasopressin (AVP), angiotensin II (AII) and met-enkephalin
      (mENK), and receive input from galanin (GAL) and vasoactive intestinal
      polypeptide (VIP) immunoreactive fibers. Neurons of the SCN core synthesize GABA,
      CALB, VIP, calretinin (CALR), gastrin releasing peptide (GRP), and neurotensin
      (NT), and receive input from the retina and from fibers that contain neuropeptide
      Y (NPY) and 5-hydroxytryptamine (5HT). Fibers projecting from SCN neurons that
      are immunoreactive for AVP and VIP exhibit a characteristic morphology, and
      project to the lateral septum, a series of medial hypothalamic areas extending
      from the preoptic to the posterior hypothalamic area and to the paraventricular
      thalamic nucleus. The organization of the mouse SCN, and its connections, are
      similar to that in other mammalian species.

PMID- 11597606
TI  - Inhibition of Na(+)/Ca(2+) exchange by KB-R7943, a novel selective antagonist,
      attenuates phosphoethanolamine and free fatty acid efflux in rat cerebral cortex
      during ischemia-reperfusion injury.
AB  - Reversal of the Na(+)/Ca(2+) exchanger (NCX) occurs during ischemia-reperfusion
      injury as a result of changes in intracellular pH and sodium concentration.
      Inhibition of NCXs has been shown to be neuroprotective in vitro. In this study,
      we evaluated the effects of KB-R7943 (50 microM), a specific inhibitor of the
      reverse mode of NCX, applied topically onto rat cerebral cortex prior to and
      during ischemia. Amino acid and free fatty acid levels in cortical superfusates,
      withdrawn at 10-min intervals from bilateral cortical windows, were analyzed by
      high-performance liquid chromatography. During a 20-min period of ischemia in
      control animals, there were significant increases in all amino acids and in all
      FFAs. Following reperfusion, all FFAs remained significantly elevated.
      Application of KB-R7943 (50 microM) significantly inhibited effluxes of
      phosphoethanolamine, but had no effect on glutamate, aspartate, taurine or GABA
      levels. KB-R7943 also resulted in significant reductions in levels of myristic,
      docosahexaenoic and arachidonic acid during ischemia and in reperfusion levels of
      arachidonic and docosahexaenoic acids. These data indicate that inhibition of
      Na(+)/Ca(2+) exchange likely prevented the activation of phospholipases that
      usually occurs following an ischemic insult as evidenced by its attenuation of
      phosphoethanolamine and free fatty acid efflux. The inhibition of phospholipases
      may be an essential component of the neuroprotective benefits of Na(+)/Ca(2+)
      exchange inhibitors in ischemia-reperfusion injury and may provide a basis for
      their possible use in therapeutic strategies for stroke.

PMID- 11597607
TI  - Changes in Ca(2+) channel expression upon differentiation of SN56 cholinergic
      cells.
AB  - The SN56 cell line, a fusion of septal neurons and neuroblastoma cells, has been
      used as a model for central cholinergic neurons. These cells show increased
      expression of cholinergic neurochemical features upon differentiation, but little
      is known about how differentiation affects their electrophysiological properties.
      We examined the changes in Ca(2+) channel expression that occur as these cells
      undergo morphological differentiation in response to serum withdrawal and
      exposure to dibutyryl-cAMP. Undifferentiated cells expressed a T-type current
      with biophysical and pharmacological properties similar, although not identical,
      to those reported for the current generated by the alpha(1H) (CaV3.2) Ca(2+)
      channel subunit. Differentiated cells expressed, in addition to this T-type
      current, high voltage activated currents which were inhibited 38% by the L-type
      channel antagonist nifedipine (5 microM), 37% by the N-type channel antagonist
      omega-conotoxin-GVIA (1 microM), and 15% by the P/Q-type channel antagonist omega
      agatoxin-IVA (200 nM). Current resistant to these inhibitors accounted for 15% of
      the high voltage activated current in differentiated SN56 cells. Our data
      demonstrate that differentiation increases the expression of neuronal type
      voltage gated Ca(2+) channels in this cell line, and that the channels expressed
      are comparable to those reported for native basal forebrain cholinergic neurons.
      This cell line should thus provide a useful model system to study the
      relationship between calcium currents and cholinergic function and dysfunction.

PMID- 11597608
TI  - Aniracetam enhances cortical dopamine and serotonin release via cholinergic and
      glutamatergic mechanisms in SHRSP.
AB  - Aniracetam, a cognition enhancer, has been recently found to preferentially
      increase extracellular levels of dopamine (DA) and serotonin (5-HT) in the
      prefrontal cortex (PFC), basolateral amygdala and dorsal hippocampus of the
      mesocorticolimbic system in stroke-prone spontaneously hypertensive rats. In the
      present study, we aimed to identify actually active substances among aniracetam
      and its major metabolites and to clarify the mode of action in DA and 5-HT
      release in the PFC. Local perfusion of mecamylamine, a nicotinic acetylcholine
      (nACh) and N-methyl-D-aspartate (NMDA) receptor antagonist, into the ventral
      tegmental area (VTA) and dorsal raphe nucleus (DRN) completely blocked DA and 5
      HT release, respectively, in the PFC elicited by orally administered aniracetam.
      The effects of aniracetam were mimicked by local perfusion of N-anisoyl-gamma
      aminobutyric acid [corrected] (N-anisoyl-GABA), one of the major metabolites of
      aniracetam, into the VTA and DRN. The cortical DA release induced by N-anisoyl
      GABA applied to the VTA was also completely abolished by co-perfusion of
      mecamylamine. Additionally, when p-anisic acid, another metabolite of aniracetam,
      and N-anisoyl-GABA were locally perfused into the PFC, they induced DA and 5-HT
      release in the same region, respectively. These results indicate that aniracetam
      enhances DA and 5-HT release by mainly mediating the action of N-anisoyl-GABA
      that targets not only somatodendritic nACh and NMDA receptors but also
      presynaptic nACh receptors.

PMID- 11597609
TI  - Hypothalamic paraventricular nucleus injections of urocortin alter food intake
      and respiratory quotient.
AB  - Corticotropin releasing hormone (CRH) acts on the central nervous system to alter
      energy balance and influence both food intake and sympathetically-mediated
      thermogenesis. CRH is also reported to inhibit food intake in several models of
      hyperphagia including neuropeptide Y (NPY)-induced eating. The recently
      identified CRH-related peptide, urocortin (UCN), also binds with high affinity to
      CRH receptor subtypes and decreases food intake in food-deprived and non-deprived
      rats. The present experiment characterized further the feeding and metabolic
      effects of UCN by examining its impact after direct injections into the
      paraventricular nucleus (PVN) of the hypothalamus. In feeding tests (n=8), UCN
      (50-200 pmol) was injected into the PVN at the onset of the dark cycle and food
      intake was measured 1, 2 and 4 h postinjection. In separate rats (n=8), the
      metabolic effects of UCN were monitored using an open circuit calorimeter which
      measured oxygen consumption (V(O2)) and carbon dioxide production (V(CO2)).
      Respiratory quotient (RQ) was calculated as V(CO2)/V(O2). UCN suppressed feeding
      at all times studied and reliably decreased RQ within 30 min of infusion.
      Additional work examined the effect of UCN (50-100 pmol) pretreatment on the
      feeding and metabolic effects of NPY. NPY, injected at the start of the dark
      period, reliably increased 2 h food intake. This effect was blocked by PVN UCN
      administration. Similarly, UCN blocked the increase in RQ elicited by NPY alone.
      These results suggest that UCN-sensitive mechanisms within the PVN may modulate
      food intake and energy substrate utilization, possibly through an interaction
      with hypothalamic NPY.

PMID- 11597610
TI  - Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerative
      disease.
AB  - Elevated levels of oxidative stress or decreased antioxidant defense mechanisms
      may underlie the regionally increased oxidative damage to brain observed in many
      neurodegenerative disorders. Phase I detoxification pathways for reactive
      aldehydes generated from lipid peroxidation include aldehyde dehydrogenases,
      alcohol dehydrogenases and aldo-keto reductases (AKR). In the present study, we
      examined the cellular expression of AKR family member, succinic semialdehyde
      reductase (AKR7A2) that reduces toxic aldehydes as well as catalyzing the
      biosynthesis of the neuromodulator gamma-hydroxybutyrate (GHB). Our results show
      that in the cerebral cortex and hippocampus, AKR7A2 is primarily localized to
      glial cells, astrocytes and microglia. In the midbrain, AKR7A2 was found in glia
      and neuromelanin-containing neurons of the substantia nigra, and the
      periaqueductal gray. In sections of cerebral cortex and hippocampus from patients
      with AD and DLB, AKR7A2 immunoreactivity was elevated in reactive astrocytes and
      microglial cells. Furthermore, total AKR7A2 protein levels were elevated in the
      cerebral cortex of patients with AD versus control individuals. Our data suggest
      that reactive gliosis, as a response to injury, may affect GHB neuromodulatory
      pathways in neurodegenerative disease and elevate aldehyde detoxification
      pathways.

PMID- 11597611
TI  - Kainate excitotoxicity in organotypic hippocampal slice cultures: evidence for
      multiple apoptotic pathways.
AB  - The mechanisms underlying kainate (KA) neurotoxicity are still not well
      understood. We previously reported that KA-mediated neuronal damage in
      organotypic cultures of hippocampal slices was associated with p53 induction.
      Recently, both bax and caspase-3 have been demonstrated to be key components of
      the p53-dependent neuronal death pathway. Caspase activation has also been
      causally related to the release of mitochondrial cytochrome c (Cyto C) in the
      cytoplasm as a result of the collapse of the mitochondrial membrane potential
      (Deltapsi(M)) and the opening of mitochondrial permeability transition pores
      (mPTP). In the present study, we observed a rapid induction of bax in hippocampal
      slice cultures after KA treatment. In addition, the levels of Cyto C and caspase
      3 were increased in the cytosol while the level of the caspase-9 precursor was
      decreased. There was also a complete reduction of Rhodamine 123 fluorescence
      after KA treatment, an indication of Deltapsi(M) dissipation. Furthermore,
      inhibition of mPTP opening by cyclosporin A partially prevented Cyto C release,
      caspase activation and neuronal death. These data suggest the involvement of bax,
      several caspases, as well as Cyto C release in KA-elicited neuronal death.
      Finally, inhibition of caspase-3 activity by z-VAD-fmk only partially protected
      neurons from KA toxicity, implying that multiple mechanisms may be involved in KA
      excitotoxicity.

PMID- 11597612
TI  - Announcing the winner of the IJGO Prize Paper Award for 2000.

PMID- 11597613
TI  - A study of intravaginal misoprostol for induction of labor in toxemia of
      pregnancy.
AB  - OBJECTIVE: To compare the efficacy and complications of intravaginal misoprostol
      for induction of labor in patients with and without toxemia of pregnancy.
      METHODS: Forty-two patients with toxemia of pregnancy (group 1) and 59 women at
      term without toxemia (group 2) with Bishop scores of < or = 6 were treated with
      50 microg intravaginal misoprostol given four times at 4-h intervals. Labor and
      neonatal outcomes, and any complications, were recorded. Mann-Whitney U-,
      Student's t- and chi(2)-tests were used for statistical analyses. P < or = 0.05
      was considered significant. RESULTS: The rates of vaginal delivery were 73.8% and
      84.6%, oxytocin augmentation were 4.8% and 5.1% and the mean insertion to
      delivery times were 12.5 and 13.8 h in group 1 and 2, respectively, with no
      significant differences between the groups. Neonatal outcomes, rates of uterine
      contraction abnormalities and gastrointestinal symptoms were similar in both
      groups. CONCLUSIONS: Intravaginal misoprostol is an equally effective and safe
      method of induction of labor in patients with toxemia of pregnancy and in normal
      pregnant women.

PMID- 11597614
TI  - Mother-to-infant transmission of TT virus in Japan.
AB  - OBJECTIVE: The TT virus (TTV) was detected for the first time by Nishizawa and
      Okamoto et al. in 1997 in the serum of a patient with post-transfusion hepatitis
      of unknown origin (non-A-non-G type). TTV was subsequently, also found in the
      serum of blood donors with no history of blood transfusion, although at a lower
      rate than among donors with a history of blood transfusion. In the present study,
      we determined the percentage of TTV carriers among pregnant women with no history
      of blood transfusion, and evaluated the possibility of mother-child transmission.
      METHODS: Blood was sampled from 300 normal pregnant women with no history of
      blood transfusion, 10 infants born by vaginal delivery from TTV-positive women,
      10 infants born by abdominal cesarean section from TTV-positive women at both 5
      days and 3 months after birth, and 10 infants born from TTV-positive women at 6
      months after birth. Amniotic fluid and breast milk were sampled from 10 and 30
      TTV-positive women, respectively. Informed consent was obtained from all women
      before sampling. TTV DNA was detected by the nested polymerase chain reaction
      (PCR) method. RESULTS: (1) Of the 300 normal pregnant women with no history of
      blood transfusion, 60 (20%) were TTV-positive. (2) All infants from TTV-positive
      mothers were TTV-negative at both 5 days and 3 months after birth, regardless of
      whether they were born by vaginal delivery or abdominal cesarean section. (3) Of
      the 10 infants who were born from TTV-positive mothers and examined 6 months
      after birth, 4 (40%) were TTV-positive. (4) Amniotic fluid from all 10 TTV
      positive women was TTV-negative. (5) Breast milk from 7 (23.3%) of the 30 TTV
      positive women was TTV-positive. CONCLUSION: TTV was detected in 20% of pregnant
      women with no history of blood transfusion, suggesting that TTV infection can
      occur through non- blood-mediated routes. The possibility of transfer of TTV into
      amniotic fluid was ruled out due to its absence in amniotic fluid samples. All
      infants from TTV-positive women were TTV-negative at both 5 days and 3 months
      after birth, regardless of whether they were born by vaginal delivery or
      abdominal cesarean section, suggesting that infection in the parturient canal or
      the pelvis is unlikely. Because TTV was detected in breast milk from TTV-positive
      women and some of their infants were TTV-positive, breast milk was thought to be
      a mother-child infection route. These findings suggest that horizontal infection
      is more likely than vertical infection in mother-child transmission of TTV.

PMID- 11597615
TI  - Myomectomy during cesarean section.
AB  - OBJECTIVES: To assess the intra- and post-operative complications of cesarean
      myomectomy. METHODS: The study design was descriptive, and the setting was the
      Department of Obstetrics and Gynaecology, University of Benin Teaching Hospital
      and two private consultant units, all in Benin City. The subjects were 25
      pregnant women undergoing elective or emergency cesarean section at these units.
      The outcome measures were blood loss and need for blood transfusion, intra- and
      post-operative complications and duration of hospital stay. RESULTS: Eighty-four
      fibroids of various sizes (2-10 cm) were removed from the 25 women. The fibroids
      were on the anterior uterine wall with most (94.8%) being sub-serous or
      intramural, and only few (five) sub-mucous. The mean blood loss was 876+/-312 ml,
      range 400-1700 ml. Five patients (20%) had two units of whole blood transfusion.
      There was no case of severe hemorrhage necessitating hysterectomy. Eighteen
      patients (72%) had post-operative morbidities mainly of anemia [15 (60%);
      hematocrit 26+/-2.9%). The average duration of post-operative hospital stay was
      7.4+/-2.2 days (range 3-12 days). Three (12%) patients have subsequently become
      pregnant, two (66.7%) of whom had normal vaginal deliveries, while the third had
      a repeat elective cesarean section. CONCLUSIONS: With adequate experience and the
      use of high dose oxytocin infusion (intra- and post-operatively), myomectomy at
      cesarean section is not as hazardous as many now believe.

PMID- 11597616
TI  - Risk factor screening for abnormal glucose tolerance in pregnancy.
AB  - OBJECTIVES: To assess the prevalence and association of frequently used screening
      risk factors for gestational diabetes mellitus (GDM) and to compare the validity
      and cost of universal screening with risk factor screening. METHOD: A cross
      sectional survey of 768 pregnant women at > or = 24 weeks' gestation who were
      attending the antenatal clinic at the Hospital Universiti Kebangsaan Malaysia
      (HUKM) was made. Risk factors were determined using a questionnaire. An abnormal
      oral glucose tolerance test was defined as a 2-h post-prandial blood sugar level
      of > or = 7.8 mmol/l. RESULTS: A total of 191 pregnant mothers (24.9%) had GDM.
      The most commonly identified screening factors were positive family history of
      diabetes mellitus (31.4%), history of spontaneous abortion (17.8%), vaginal
      discharge and pruritus vulvae in current pregnancy (16.0%), and maternal age
      greater than 35 years (14.7%). Five hundred and thirteen mothers (66.8%) had at
      least one risk factor. All screening risk factors, except past history of
      diabetes mellitus in previous pregnancy and maternal age, were not significantly
      associated with abnormal glucose tolerance (GT). Risk factor screening gave a
      sensitivity of 72.2% and a specificity of 35.0%. Universal screening would cost
      RM 12.06 while traditional risk factor screening would cost RM 11.15 per
      identified case and will have missed 53 of the 191 cases. CONCLUSIONS: Risk
      factor screening scored poorly in predicting GDM. Cost analysis of universal
      compared with traditional risk factor screening showed a negligible difference.
      Thus universal screening appears to be the most reliable method of diagnosing
      GDM.

PMID- 11597617
TI  - Prognostic factors related to cervical cancer survival in Mexican women.
AB  - OBJECTIVE: To identify prognostic survival factors among Mexican women with
      cervical cancer. METHODS: A total of 378 women with cervical cancer admitted from
      1984 to 1996 to our referral hospital were evaluated, using survival analysis
      (Kaplan-Meier and Cox proportional hazards method). We designed a symptom index
      which included asymptomatic conditions, severity of symptoms and comorbidity.
      RESULTS: Overall 5-year survival was 66.6%. The shortest survival time was for
      FIGO stage IV (21.5%, P<0.001) and adenosquamous histologic type (53.1%, P=0.15).
      The main prognostic factors were primary symptoms (RR, 2.6; 95% CI, 1.02-6.66);
      systemic symptoms (RR, 3.3; 95% CI, 1.23-9.01); FIGO stage IV (RR, 5.5; 95% CI,
      2.36-12.96); and oncogenic symptoms (prognostic comorbidity present) (RR, 2.3;
      95% CI, 1.08-4.89). CONCLUSIONS: Our findings show that clinical stage and
      several types of symptoms influence CC survival. This present strategy to assess
      morphological and clinical characteristics may be a more accurate indicator of
      survival rate and potentially an efficient indicator of new therapeutic
      alternatives.

PMID- 11597618
TI  - Insulin resistance in clomiphene responders and non-responders with polycystic
      ovarian disease and therapeutic effects of metformin.
AB  - OBJECTIVES: To evaluate the clinical features, endocrine and metabolic profiles
      in clomiphene (CC) responders and non-responders with polycystic ovarian disease
      (PCOD), and to examine the effects of metformin (MTF) on the above parameters of
      CC resistance. METHODS: A prospective clinical trial was undertaken at the
      infertility division of a university teaching hospital. Forty-one CC responders
      were selected and their hormonal and clinical features were determined. Forty-one
      CC-resistant PCOD women were also selected and clinical features; metabolic and
      hormonal profiles before and after treatment with MTF 1500 mg/day for 6-8 weeks
      were evaluated. Women who failed to conceive were treated by CC while continuing
      to take MTF. RESULTS: CC responders had higher insulin levels while non
      responders were hyperinsulinemic. Menstrual irregularities improved in 30%.
      Mean+/-S.D. area under curve of insulin decreased from 297.58+/-191.33 to 206+/
      0.1 mIU/ml per min (P=0.005). Only 39.39% ovulated and 24.24% conceived.
      CONCLUSION: PCOD is associated with insulin resistance (IR) particularly in CC
      resistant women. Insulin resistance and androgen levels are significantly higher
      in obese patients. MTF therapy improved hyperandrogenemia, IR, and pregnancy
      rate.

PMID- 11597619
TI  - Using human rights in maternal mortality programs: from analysis to strategy.
AB  - This article describes an approach to maternal mortality reduction that uses
      human rights not simply to denounce the injustice of death in pregnancy and
      childbirth, but also to guide the design and implementation of maternal mortality
      policies and programs. As a first principle, programs and policies need to
      prioritize measures that promote universal access to high quality emergency
      obstetric care services, which we know from health research are essential to
      saving women's lives. With that priority, human rights principles can be
      integrated into programs at the clinical, facility management, and national
      policy levels. For example, a human rights 'audit' can help identify ways to
      encourage respectful, non-discriminatory treatment of patients, providers and
      staff in the clinical setting. Human rights principles of entitlement and
      accountability can inform mechanisms of community participation designed to
      improve responsiveness and functioning of health facilities. Human rights
      principles can inform analysis of health sector reform and its impact on access
      to emergency obstetric care. Whether applied to the intricacies of human
      relationships within a facility or to the impact of international financial
      institutions on health systems, the ultimate role of human rights is to identify
      the workings of power that keep unacceptable levels of maternal morality as they
      are and to use the human rights vision of dignity and social justice to work for
      the re-arrangements of power necessary for change.

PMID- 11597621
TI  - Monitoring obstetric services: putting the 'UN Guidelines' into practice in
      Malawi: 3 years on.
AB  - The maternal mortality ratio is difficult to use for monitoring short-term
      progress in safe motherhood programs. UNICEF/WHO/UNFPA have proposed alternative
      process indicators monitoring the availability, utilization and quality of
      obstetric services. There is little experience in the large-scale use of these
      indicators as part of routine health information systems in developing countries.
      The Malawi Safe Motherhood Project, which covers a population of over 5 million,
      was one of the first large projects to implement the new process indicators. At
      the end of 2000 data were available from the new monitoring system for 3
      consecutive years. In 1998, availability of comprehensive emergency obstetric
      care was adequate but availability of basic emergency obstetric care was very
      poor. Although institutional delivery rates were over 30%, the met need for
      obstetric care was only 19.8% and the cesarean section rate was only 1.6%. The
      mean case fatality rate in District hospitals was nearly 5%. By the end of 2000,
      improvements in availability, utilization and quality of obstetric care were
      observed. Participation in developing the monitoring system had also created a
      strong sense of ownership and interest in analyzing and using the data. Several
      issues have emerged from routine use of the process indicators. In particular, it
      has been difficult to be certain that obstetric complications have been recorded
      correctly. The results confirm that a focus on improving emergency obstetric care
      in Malawi was justified and that process indicators for obstetric care can be
      successfully introduced in developing countries. The monitoring system has
      provided data that are of immediate relevance to service providers, managers, and
      policy makers and provide many lessons useful for similar programs in other
      settings.

PMID- 11597623
TI  - Serum nitric oxide changes in spontaneous and induced labor.

PMID- 11597624
TI  - Maternal morbidity during labor in Mulago hospital.

PMID- 11597625
TI  - Reproductive tract infections in pregnant women in Delhi, India.

PMID- 11597626
TI  - Serotonin in pre-eclampsia.

PMID- 11597627
TI  - Papillary serous cystadenofibroma of the ovary--is it really so rare?

PMID- 11597628
TI  - Contraceptive use and method choice in Turkey.

PMID- 11597629
TI  - Indifference and resignation of Japanese women toward urinary incontinence.

PMID- 11597631
TI  - Contemporary management of subarachnoid hemorrhage and vasospasm: the UIC
      experience.
AB  - BACKGROUND: Cerebral vasospasm is a well-known and serious complication of
      aneurysmal subarachnoid hemorrhage. The means of monitoring and treatment of
      vasospasm have been widely studied. Each neurosurgical center develops a protocol
      based on their experience, availability of equipment and personnel, and cost, so
      as to keep morbidity and mortality rates as low as possible for their patients
      with vasospasm. METHODS: At the University of Illinois at Chicago, we have
      developed algorithms for the diagnosis and management of cerebral vasospasm based
      on the experience of the senior authors over the past 25 years. This paper
      describes in detail our approach to diagnosis and treatment of aneurysmal
      subarachnoid hemorrhage and vasospasm. Our discussion is highlighted with data
      from a retrospective analysis of 324 aneurysm patients. RESULTS: Over 3 years,
      324 aneurysms were treated; 185 (57%) were clipped, 139 (43%) were coiled. The
      rate of vasospasm for the 324 patients was 27%. The rate of hydrocephalus was 32%
      for those patients who underwent clipping, and 29% for those coiled. The
      immediate outcomes for those who underwent clipping was excellent in 35%, good in
      38%, poor in 15.5%, vegetative in 3%, and death in 8% of the patients. For those
      who underwent coiling the immediate outcome was excellent in 64%, good in 14.5%,
      vegetative in 2.5%, and death in 14.5% of the patients. These statistics include
      all Hunt and Hess grades. For those patients who underwent clipping, 51% were
      intact at 6 months follow-up, 15% had a permanent deficit, 10% had a focal
      cranial nerve deficit, and 2% had died from complications not directly related to
      the procedure. For those patients who had undergone coiling, 75% were intact at 6
      months follow-up, 12.5% had a permanent deficit, and 12.5% had a cranial nerve
      deficit, with no deaths. CONCLUSIONS: The morbidity and mortality of cerebral
      vasospasm is significant. A good outcome after aneurysmal subarachnoid hemorrhage
      is dependent upon careful patient management in the preoperative, perioperative,
      and postoperative periods. The timely work-up and aggressive treatment of
      neurological deterioration, whether or not it is because of vasospasm, is
      paramount.

PMID- 11597636
TI  - The influence of surgical experience on the rate of intraoperative aneurysm
      rupture and its impact on aneurysm treatment outcome.
AB  - BACKGROUND: The influence of surgical experience on the result of aneurysm
      surgery remains unclear. To determine the impact of surgical experience we
      considered the occurrence of intraoperative aneurysm rupture (IAR) during
      microneurosurgery for intracranial aneurysms as an objective factor that could be
      evaluated. METHODS: A retrospective study was performed on 379 consecutive
      patients with 490 cerebral aneurysms operated upon from 1989 to 1995. RESULTS:
      IAR occurred in 6.7% of aneurysms and 8.7% of patients. There was a direct
      inverse relationship between the annual caseload of the surgeon and the risk of
      IAR. New neurological deficits (NND) occurred in 21% of patients with IAR, which
      accounts for 1.8% of NND in all patients with aneurysms. CONCLUSION: Although
      there seems to be a direct relationship between surgical experience and the risk
      of IAR, the impact on the overall treatment outcome of cerebral aneurysms is
      rather limited.

PMID- 11597640
TI  - Intra-arterial papaverine-induced seizures: case report and review of the
      literature.
AB  - BACKGROUND: Microcatheter-guided intra-arterial (IA) papaverine infusion in
      conjunction with balloon angioplasty is an available therapy for patients with
      symptomatic vasospasm after subarachnoid hemorrhage (SAH) that is refractory to
      hypertensive, hypervolemic therapy. However, side effects and complications have
      been reported in association with its use. CASE DESCRIPTION: We report on a
      patient who developed symptomatic vasospasm after subarachnoid hemorrhage due to
      rupture of a left terminal internal carotid artery (ICA) saccular aneurysm. Seven
      days after the hemorrhage and 4 days after surgical clipping, the patient
      developed aphasia and right hemiparesis due to vasospasm, which was refractory to
      maximal medical treatment with volume and blood pressure elevation. Cerebral
      angiography identified severe narrowing of distal ICA and proximal middle
      cerebral artery segments bilaterally. These findings partially resolved after
      balloon angioplasty. However, after 300 mg of IA papaverine, the patient
      developed generalized convulsions. This occurred despite therapeutic serum levels
      of phenytoin. Twenty-four hours later, after brief neurologic improvement,
      recurrent neurologic deficits prompted repeat papaverine administration. Seizures
      again occurred after the administration of 240 mg of IA papaverine and prevented
      administration of the full dose. The patient did not develop further seizures and
      her neurologic deficits continue to resolve. CONCLUSIONS: IA papaverine-induced
      seizures are infrequently reported. This potential complication should be
      considered when papaverine administration is entertained in the treatment of
      anterior circulation refractory symptomatic vasospasm after SAH.

PMID- 11597642
TI  - The tandem bypass: subclavian artery-to-middle cerebral artery bypass with dacron
      and saphenous vein grafts. Technical case report.
AB  - BACKGROUND: Fusiform or dolichoectatic intracranial aneurysms often cannot be
      managed with conventional surgical or endovascular techniques, and instead
      require trapping and revascularization techniques. On rare occasions in elderly
      patients, extracranial sites used for anastomosing the bypass have been
      previously repaired with synthetic vascular prostheses. This circumstance in an
      elderly subarachnoid hemorrhage patient led to a novel bypass procedure, the
      tandem bypass: a long extracranial-to-intracranial bypass with two grafts of
      different materials assembled in series. CASE DESCRIPTION: A 71-year-old man with
      carotid artery atherosclerotic disease and a previous vascular reconstruction
      (subclavian artery-to-internal carotid artery Dacron interposition graft)
      presented with a subarachnoid hemorrhage from a dolichoectatic supraclinoid ICA
      aneurysm. The aneurysm was treated with trapping and distal revascularization.
      The final construct was a subclavian artery-to-middle cerebral artery bypass,
      with the graft being the previous Dacron prosthesis and a long saphenous vein.
      The vein graft was anastomosed end-to-side to the Dacron graft proximally, and
      end-to side to the middle cerebral artery distally. Subsequently, inflow to the
      aneurysm was occluded with clips on the Dacron graft beyond the proximal
      anastomosis of the vein graft, and outflow from the aneurysm was occluded with
      clips on the supraclinoid ICA. CONCLUSIONS: The tandem bypass, which uses
      prosthetic graft material and saphenous vein in succession, is a technically
      straightforward technique in patients who need extracranial-to-intracranial
      bypasses and who also have pre-existing carotid reconstructions or lack
      sufficient saphenous vein to complete a long bypass.

PMID- 11597644
TI  - Venous malformation serving as the draining vein of an adjoining arteriovenous
      malformation. Case report and review of the literature.
AB  - BACKGROUND: Widely accepted pathologic classification of venous malformations
      includes discrete venous, arteriovenous, capillary, and cavernous malformations,
      each with distinct pathological criteria for definition. Several authors have
      described mixed or transitional vascular malformations with pathological features
      of more than one type of malformation within the same lesion. We present a rare
      case of a venous malformation associated with an arteriovenous malformation
      (AVM). CASE DESCRIPTION: A 37-year-old woman presented with a loss of
      consciousness. Computed tomography showed an enlarged vein running along the
      lateral wall of the right lateral ventricle. A cerebral angiogram demonstrated an
      AVM and a venous malformation in the right hemisphere; the AVM and the venous
      malformation were located in proximity to each other with the AVM using the
      venous malformation as its draining vein. In this case, where an AVM used the
      venous malformation as the draining vein, only the AVM was treated by proton-beam
      radiosurgery. Follow-up magnetic resonance angiography demonstrated complete
      obliteration of the AVM with the venous malformation remaining unchanged.
      CONCLUSION: Arteriovenous shunting would have disturbed venous drainage resulting
      in the development of the venous malformation. Thus, in addition to demonstrating
      a rare coexistence of AVM and venous malformation, this case also offers a new
      insight into the pathogenesis of these vascular malformations.

PMID- 11597645
TI  - Spinal dural arteriovenous fistula with supply from sacral arteries.

PMID- 11597647
TI  - Anterior cervical discectomy and fusion.

PMID- 11597648
TI  - Dorsal spine injuries in Saudi Arabia--an unusual cause.
AB  - BACKGROUND: Motor vehicle accidents are the most common cause of spinal injuries
      in Saudi Arabia. Camel collisions usually result in cervical spine injuries.
      Although extremely rare, dorsal spine injuries have also resulted from these
      accidents. METHOD: Retrospective analysis of the type of accident of all the
      patients with dorsal spine injuries was conducted at the supra-regional spinal
      injuries rehabilitation unit in Riyadh. RESULTS: Of all the patients' records
      reviewed, three patients' injuries to the dorsal spine had resulted from car
      accidents involving a camel. These patients, during further interviews, described
      in detail the exact mechanism of their injuries. Protective lateral bending to
      avoid the direct impact of the animal resulted in their injuries. CONCLUSION:
      Camel collisions remain a significant cause of mortality and morbidity although
      they affect the cervical spine most often. Dorsal spine injuries can result from
      protective lateral bending in unrestrained drivers and passengers.

PMID- 11597649
TI  - Improvement of chronic hearing loss after shunt revision. A case report.
AB  - BACKGROUND: Hearing loss after intracranial and spinal procedures involving
      cerebrospinal fluid loss is rarely reported in the literature. We report a
      patient who suffered from delayed hearing loss after cerebrospinal fluid shunting
      that improved after revising the shunt to a higher-pressure valve. CASE
      DESCRIPTION: A 32-year-old woman presented with bilateral hearing loss 4 years
      after ventriculoperitoneal shunting for communicating hydrocephalus. Her otologic
      work-up revealed sensorineural hearing loss. In an attempt to improve her
      hearing, 6 years after the hearing loss began (10 years after the shunt was
      placed), she underwent a shunt revision in which her valve was changed to a
      higher-pressure device. After the procedure, she had a significant improvement in
      her speech discrimination and a mild improvement in her pure tone recognition.
      These changes were documented with serial audiograms. CONCLUSION: Hearing loss
      after cerebrospinal shunting procedures is not always limited to the immediate
      postoperative period. It may be a late complication of cerebrospinal fluid
      diversion. Chronic hearing loss after ventriculoperitoneal shunting may be
      treatable by changing the valve to a higher-pressure device. The etiology of
      hearing loss from intracranial hypotension is briefly discussed.

PMID- 11597651
TI  - Streptococcal brain abscess: analysis of clinical features in 20 patients.
AB  - BACKGROUND: To assess the clinical features and therapeutic outcomes of brain
      abscess caused by streptococci. METHODS: Twenty patients, 18 males and 2 females,
      aged 3 to 76 years, collected over a 14-year period, have been identified at
      Kaohsiung Chang Gung Memorial Hospital. RESULTS: Among these 20 patients, 13 had
      viridans streptococci infection alone, one had non-A, non-B, and non-D
      streptococci infection alone, and the other 6 had mixed infections each including
      streptococci. The locations of all of the abscesses were supratentorial. Among
      these patients, 18 had a single abscess and 2 had multiple abscesses. Underlying
      conditions were common in our patients, including head trauma, heart disease,
      otopharyngeal infection, and medical procedures. Nineteen patients were treated
      surgically and 1 was treated with antibiotics alone. Nineteen survived and 1
      died, with an overall mortality rate of 5%. CONCLUSION: The clinical
      presentations and underlying conditions varied according to the different
      streptococcal species. Streptococcal brain abscesses accounted for 17% of our
      cases with brain abscesses, and 30% of our streptococcal infections had
      polymicrobial infections. Although streptococcal brain abscesses were commonly
      associated with otopharyngeal infections or infectious endocarditis, they also
      appeared to be often related to neurosurgical events or medical procedures in
      recent years. Based on our study, prognosis is favorable with early diagnosis and
      prompt treatment.

PMID- 11597654
TI  - Lhermitte-Duclos disease is a clinical manifestation of Cowden's syndrome.
AB  - BACKGROUND: Lhermitte-Duclos disease (LDD) is a hamartomatous overgrowth of
      cerebellar ganglion cells, which replace granular cells and Purkinje cells. In
      recent years several cases involving the association between LDD and Cowden's
      syndrome (CS), an autosomal dominant condition characterized by multiple
      hamartomas and neoplastic lesions in skin and internal organs, have been
      reported. METHODS: We reviewed the medical records and imaging studies of six
      patients with LDD who were treated at our institution, and we looked at other
      possible symptoms of CS. RESULTS: Other clinical findings suggestive of CS were
      apparent in five patients: These included mucocutaneous lesions, acral keratosis,
      thyroid adenoma, fibrocystic disease, ovarian cyst, intestinal polyposis, and
      arteriovenous malformation. Only in the youngest patient, a 5-year-old boy, were
      no cutaneous or other signs found, despite extensive clinical and ultrasound
      examination. CONCLUSION: Our observations strengthen the hypothesis that LDD is a
      neurological manifestation of CS. Patients with LDD should receive a thorough
      dermatological and systemic screening, because some of the lesions (breast,
      etc...) can develop into malignant tumors.

PMID- 11597652
TI  - Aspergillus parasellar abscess mimicking radiation-induced neuropathy. Case
      report.
AB  - BACKGROUND: Transsphenoidal surgery is a safe procedure for treatment of
      pituitary adenomas. However, several complications, including post-surgical
      infection, are known. We describe a case of Aspergillus parasellar abscess that
      presented with cranial neuropathies following transsphenoidal surgery and
      radiosurgery. We initially diagnosed the case as radiation-induced neuropathies,
      which delayed the detection of Aspergillus. CASE DESCRIPTION: A 55-year-old man
      underwent transsphenoidal surgery for a pituitary adenoma that presented with
      pituitary apoplexy. Dexamethasone had been continuously administered for
      hypocortisolism probably caused by pituitary apoplexy. Four years later,
      radiosurgery was performed for a relapse in the right cavernous sinus. Another 4
      years later, he developed painful right ophthalmoplegia, right ptosis, and
      bilateral visual impairment, successively. We initially suspected that the
      painful ophthalmoplegia and ptosis were because of radiation-induced cranial
      neuropathies; however, results of magnetic resonance (MR) imaging and his
      clinical course were not consistent with those of radiation-induced neuropathies.
      Therefore, we performed exploratory surgery that revealed a subdural abscess on
      the planum sphenoidale. Culture of a specimen grew Aspergillus fumigatus.
      CONCLUSION: Intracranial fungal abscess is a fatal complication unless it is
      treated early. It is thus important to consider the possibility of parasellar
      infection and differentiate it from radiation-induced cranial neuropathies when a
      patient presents with cranial neuropathies after transsphenoidal surgery and
      radiosurgery.

PMID- 11597656
TI  - Propofol versus isoflurane anesthesia under hypothermic conditions: effects on
      intracranial pressure and local cerebral blood flow after diffuse traumatic brain
      injury in the rat.
AB  - BACKGROUND: The aim of this study was to compare the cerebral protective effects
      of two known protective anesthetics, isoflurane and propofol, when these were
      used in combination with moderate hypothermia (33-34 degrees C) after diffuse
      traumatic brain injury (TBI) in the rat. We assessed cerebral protection by
      measuring local cerebral blood flow (LCBF), mean arterial blood pressure (MABP),
      cerebral perfusion pressure (CPP) and intracranial pressure (ICP). METHODS:
      Sixteen female Wistar rats weighing 275 to 350 g were anesthetized and subjected
      to an accelerated-impact weight-drop model of diffuse TBI. Hypothermia (33-34
      degrees C) was induced 45 minutes after TBI (baseline), and was maintained for
      180 minutes. The isoflurane group (n = 8) received 70% N(2)O in O(2), and
      isoflurane at 0.9 +/- 0.04%. The propofol group (n = 8) received 70% N(2)O in
      O(2) and a propofol infusion (12 mg/kg/hr). LCBF was measured by laser Doppler
      flowmeter. MABP, ICP, and brain and rectal temperatures were measured every 15
      minutes from baseline through 180 minutes. Blood gas and hematocrit testing was
      also done at baseline and every 60 minutes thereafter to assess the animals'
      physiological state. RESULTS: In the isoflurane group, MABP and CPP decreased
      significantly from baseline to 180 minutes (p < 0.05 and p < 0.01, respectively),
      and MABP was significantly lower than the pressure in the propofol group from 45
      minutes through 180 minutes (p < 0.05, p < 0.01). ICP and LCBF remained unchanged
      in this group. In the propofol group, from baseline to 180 minutes, CPP increased
      to maximum 120 +/- 8 mmHg at 75 minutes from 98 +/- 5 mmHg (p < 0.05) and ICP
      fell from 18 +/- 2 mmHg to 7 +/- 1 mmHg (p < 0.01); and the latter was
      significantly lower than ICP in the isoflurane group (p < 0.05, p < 0.01, p <
      0.001). LCBF in this group was significantly higher than LCBF in the isoflurane
      group in the last 30 minutes of the experiment (p < 0.05). The propofol group
      showed no change in MABP over the course of the experiment. CONCLUSION: In the
      clinical setting, propofol anesthesia may be better for use in combination with
      hypothermia in cases of traumatic brain injury, as it reduces ICP and increases
      CPP under these conditions.

PMID- 11597657
TI  - A solution for the present state of neurosurgery practice.

PMID- 11597658
TI  - How (not) to improve a health service.

PMID- 11597659
TI  - Public health: a neglected counterterrorist measure.

PMID- 11597660
TI  - Endothelin-receptor antagonists in pulmonary hypertension.

PMID- 11597661
TI  - Vascular calcification in chronic renal failure.

PMID- 11597662
TI  - Bradykinin in protection against left-ventricular hypertrophy.

PMID- 11597663
TI  - Darwin the philosopher?

PMID- 11597664
TI  - Effects of the dual endothelin-receptor antagonist bosentan in patients with
      pulmonary hypertension: a randomised placebo-controlled study.
AB  - BACKGROUND: Endothelin 1, a powerful endogenous vasoconstrictor and mitogen,
      might be a cause of pulmonary hypertension. We describe the efficacy and safety
      of bosentan, a dual endothelin-receptor antagonist that can be taken orally, in
      patients with severe pulmonary hypertension. METHODS: In this double-blind,
      placebo-controlled study, 32 patients with pulmonary hypertension (primary or
      associated with scleroderma) were randomly assigned to bosentan (62.5mg taken
      twice daily for 4 weeks then 125 mg twice daily) or placebo for a minimum of 12
      weeks. The primary endpoint was change in exercise capacity. Secondary endpoints
      included changes in cardiopulmonary haemodynamics, Borg dyspnoea index, WHO
      functional class, and withdrawal due to clinical worsening. Analysis was by
      intention to treat. FINDINGS: In patients given bosentan, the distance walked in
      6 min improved by 70 m at 12 weeks compared with baseline, whereas it worsened by
      6 m in those on placebo (difference 76 m [95% CI 12-139], p=0.021). The
      improvement was maintained for at least 20 weeks. The cardiac index was 1.0 L
      min(-1) m(-2) (95% CI 0.6-1.4, p<0.0001) greater in patients given bosentan than
      in those given placebo. Pulmonary vascular resistance decreased by 223 dyn s cm(
      )(5) with bosentan, but increased by 191 dyn s cm(-5) with placebo (difference 
      415 [-608 to -221], p=0.0002). Patients given bosentan had a reduced Borg
      dyspnoea index and an improved WHO functional class. All three withdrawals from
      clinical worsening were in the placebo group (p=0.033). The number and nature of
      adverse events did not differ between the two groups. INTERPRETATION: Bosentan
      increases exercise capacity and improves haemodynamics in patients with pulmonary
      hypertension, suggesting that endothelin has an important role in pulmonary
      hypertension.

PMID- 11597665
TI  - Quality assessment of 26,304 herniorrhaphies in Denmark: a prospective nationwide
      study.
AB  - BACKGROUND: Groin hernia repair is one of the most frequent operations, but there
      is no consensus about surgical or anaesthetic technique. Furthermore, no
      nationwide studies have been done. Our aim was to investigate outcome results of
      groin hernia surgery to improve quality of treatment. METHODS: We prospectively
      recorded 26304 groin hernia repairs done in Denmark from Jan 1, 1998, to June 30,
      2000, in a nationwide Danish hernia database. FINDINGS: 93% of all groin
      herniorrhaphies done in Denmark in the 30 months of the study were recorded in
      the database. Kaplan-Meier estimates of reoperation rates 30 months after
      anterior mesh repair and laparoscopic repair were significantly lower than after
      sutured posterior wall repairs in primary inguinal hernia (2.2% and 2.6% vs 4.4%;
      p<0.0001). Reoperation rates were also lower with anterior mesh repair (6.1%;
      p<0.0001) and laparoscopic repair (3.4%; p<0.0001) than with sutured posterior
      wall repair (10.6%) after recurrent hernia. Use of Lichtenstein mesh repair
      increased from 33% in January, 1998, to 62% in June, 2000, whereas use of
      laparoscopic repair remained constant at about 5%. Kaplan-Meier estimates of
      reoperation rates were 2.8% in the first 15 months and 1.6% in the second
      (p=0.03). For elective repairs, only 59% of patients were treated on an
      outpatient basis, and only 18% had local anaesthesia. INTERPRETATION: Mesh
      repairs have a lower reoperation rate than conventional open repairs. Systematic
      prospective recording of treatment and outcome variables in a national clinical
      database improved the overall quality of surgical care. However, there is a large
      potential for cost savings and more efficient patient care with extended use of
      mesh techniques, outpatient surgery, and local anaesthesia.

PMID- 11597666
TI  - Exposure to farming in early life and development of asthma and allergy: a cross
      sectional survey.
AB  - BACKGROUND: A farming environment protects against development of asthma, hay
      fever, and atopic sensitisation in children. We aimed to establish whether
      increased exposure to microbial compounds has to occur early in life to affect
      maturation of the immune system and thereby reduces risk for development of
      allergic diseases. METHODS: We did a cross-sectional survey in rural areas of
      Austria, Germany, and Switzerland. 2618 (75%) of 3504 parents of 6-13-year-old
      children completed a standardised questionnaire on asthma, hay fever, and atopic
      eczema. Children from farming families, and a random sample of non-farmers'
      children, who gave consent for blood samples to be obtained for measurements of
      specific serum IgE antibodies to common allergens were invited to participate
      (n=901). FINDINGS: Exposure of children younger than 1 year, compared with those
      aged 1-5 years, to stables and consumption of farm milk was associated with lower
      frequencies of asthma (1% [3/218] vs 11% [15/138]), hay fever (3% [7] vs 13%
      [18]), and atopic sensitisation (12% [27] vs 29% [40]). Protection against
      development of asthma was independent from effect on atopic sensitisation.
      Continual long-term exposure to stables until age 5 years was associated with the
      lowest frequencies of asthma (0.8% [1/122]), hay fever (0.8% [1]), and atopic
      sensitisation (8.2% [10]). INTERPRETATION: Long-term and early-life exposure to
      stables and farm milk induces a strong protective effect against development of
      asthma, hay fever, and atopic sensitisation.

PMID- 11597667
TI  - Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk
      in Communities Study.
AB  - BACKGROUND: Retinal microvascular abnormalities reflect damage from hypertension
      and other vascular processes. We examined the relation of such abnormalities to
      incident stroke. METHODS: A cohort of 10358 men and women (aged 51 to 72 years)
      living in four US communities underwent retinal photography and standard grading
      for retinal microvascular abnormalities. The calibres of all retinal arterioles
      and venules were measured after digital conversion of the photographs, and a
      summary arteriole-to-venule ratio (AVR) was calculated as an index of arteriolar
      narrowing (smaller AVR indicates greater narrowing). Cases of incident stroke
      admitted to hospital were identified and validated by case record reviews.
      FINDINGS: Over an average of 3.5 years, 110 participants had incident strokes.
      After adjustment for age, sex, race, 6-year mean arterial blood pressure,
      diabetes, and other stroke risk factors, most retinal microvascular
      characteristics were predictive of incident stroke, with adjusted relative risks
      of 2.58 (1.59-4.20) for any retinopathy, 3.11 (1.71-5.65) for microaneurysms,
      3.08 (1.42-6.68) for soft exudates, 2.55 (1.27-5.14) for blot haemorrhages, 2.26
      (1.00-5.12) for flame-shaped haemorrhages, and 1.60 (1.03-2.47) for arteriovenous
      nicking. The relative risk of stroke increased with decreasing AVR (p=0.03). The
      associations were similar for ischaemic strokes specifically, and for strokes in
      individuals with hypertension, either with or without diabetes. INTERPRETATION:
      Retinal microvascular abnormalities are related to incident stroke. The findings
      support a microvascular role in the pathogenesis of stroke. They suggest that
      retinal photography may be useful for cerebrovascular-risk stratification in
      appropriate populations.

PMID- 11597668
TI  - Direct-to-consumer advertisements for prescription drugs: what are Americans
      being sold?
AB  - BACKGROUND: Pharmaceutical companies spent US$1.8 billion on direct-to-consumer
      advertisements for prescription drugs in 1999. Our aim was to establish what
      messages are being communicated to the public by these advertisements. METHODS:
      We investigated the content of advertisements, which appeared in ten magazines in
      the USA. We examined seven issues of each of these published between July, 1998,
      and July, 1999. FINDINGS: 67 advertisements appeared a total of 211 times during
      our study. Of these, 133 (63%) were for drugs to ameliorate symptoms, 54 (26%) to
      treat disease, and 23 (11%) to prevent illness. In the 67 unique advertisements,
      promotional techniques used included emotional appeals (45, 67%) and
      encouragement of consumers to consider medical causes for their experiences (26,
      39%). More advertisements described the benefit of medication with vague,
      qualitative terms (58, 87%), than with data (9, 13%). However, half the
      advertisements used data to describe side-effects, typically with lists of side
      effects that generally occurred infrequently. None mentioned cost.
      INTERPRETATION: Provision of complete information about the benefit of
      prescription drugs in advertisements would serve the interests of physicians and
      the public.

PMID- 11597669
TI  - Risk factors, atherosclerosis, and cardiovascular disease among Aboriginal people
      in Canada: the Study of Health Assessment and Risk Evaluation in Aboriginal
      Peoples (SHARE-AP).
AB  - BACKGROUND: Little is known about the rates of cardiovascular disease (CVD),
      atherosclerosis, and their risk factors among Canada's Aboriginal people. To
      establish the relative prevalence of risk factors, atherosclerosis, and CVD, we
      undertook a population-based study among people of Aboriginal and European
      ancestry in Canada. METHODS: We randomly recruited 301 Aboriginal people from the
      Six Nations Reservation, and 326 people of European origin from Hamilton,
      Toronto, and Edmonton, Canada. Clinical CVD was defined by history or
      electrocardiographic findings, atherosclerosis was measured by B-mode carotid
      ultrasonography, and conventional and new CVD risk factors were measured using
      standardised methods. FINDINGS: Aboriginal people had significantly more carotid
      atherosclerosis (mean of the maximum intimal-medial thickness 0.82 (SD 0.20) mm
      vs 0.78 (0.20) mm, p=0.027), and had a higher frequency of CVD (18.5% vs 7.6%,
      p=0.00002) compared with Europeans. Aboriginal people had significantly higher
      rates of smoking, glucose intolerance, obesity, abdominal obesity, and
      substantially higher concentrations of fibrinogen, and plasminogen activator
      inhibitor-1. Aboriginal people had significantly higher rates of unemployment and
      a lower annual household income. For any given income level, Aboriginal people
      had higher rates of risk factors and CVD compared with the Europeans.
      INTERPRETATION: A significant proportion of Aboriginal people live in poverty
      which is associated with high rates of CVD and CVD risk factors. Improvement of
      the socioeconomic status of Aboriginal people might be a key to reduce CVD in
      this group.

PMID- 11597671
TI  - A woman with vomiting and depression.

PMID- 11597672
TI  - Bradykinin B2BKR receptor polymorphism and left-ventricular growth response.
AB  - Angiotensin-converting-enzyme (ACE) activity regulates left-ventricular growth.
      The deletion (D), rather than the insertion (I), ACE gene variant is associated
      with increased ACE activity and kinin degradation, and the absence (-) rather
      than the presence (+) of a 9 bp deletion in the gene encoding the bradykinin 2
      receptor (B2BKR) is associated with greater gene expression. We determined the
      ACE and B2BKR genotype of 109 male army recruits, and measured their
      physiological left-ventricular growth response to a 10-week physical training
      programme. Mean left-ventricular growth was 15.7 g (SE 3.5) in those with ACE
      genotype D/D and B2BKR genotype +9/+9, but -1.37 g (4.1) in those with ACE
      genotype I/I and B2BKR genotype -9/-9 (p=0.003 for trend across genotypes). These
      results suggest that kinins regulate left-ventricular growth, mediating some of
      the effects of ACE in this regard.

PMID- 11597673
TI  - The importance of both an early orchidopexy and germ cell maturation for
      fertility.
AB  - Delayed orchidopexy for undescended testes has been associated with abnormal
      testicular histology, but the effect on later fertility is unknown. We aimed to
      establish the importance of the first postnatal maturational step-ie, the
      transformation of gonocytes into Ad (dark) spermatogonia on fertility. We matched
      histological findings of the testes from 31 patients who had undergone an early
      orchidopexy with their total number of sperm. If Ad spermatogonia were present,
      17 (94%) of 18 (95% CI 72.7-99.9) of the men had a total sperm count of 40 x
      10(6)/ejaculate or greater. By contrast, despite successful early surgery, if Ad
      spermatogonia were absent, 12 (92%) of 13, (64.0-99.8) patients had abnormal
      spermiograms. Thus, the transformation of gonocytes into Ad spermatogonia is
      crucial for male fertility.

PMID- 11597674
TI  - Survival after bone marrow transplantation from cytomegalovirus seropositive
      sibling donors.
AB  - HLA-A2-restricted T cells show peptide-specific activity against cytomegalovirus
      and leukaemia cells. We retrospectively analysed the influence of donor
      cytomegalovirus serostatus on the outcome of 103 consecutive patients who had
      leukaemia and who received bone-marrow transplants from HLA-identical sibling
      donors. We found that donor cytomegalovirus seropositivity significantly improved
      overall survival (p=0.02) as a result of lower relapse incidence (p=0.035) in HLA
      A2-positive but not HLA-A2-negative recipients. In HLA-A2-positive recipients
      donor cytomegalovirus seropositivity was associated with chronic graft-versus
      host disease (GVHD), but even in patients without chronic GVHD donor
      cytomegalovirus seropositivity significantly improved survival (p=0.0483). These
      preliminary data provide evidence that at least in HLA-A2-positive recipients,
      transplantation of bone marrow from cytomegalovirus positive, HLA-identical
      sibling donors seems to be associated with substantial graft-versus-leukaemia
      activity, and suggests a cross-reactivity of cytomegalovirus-specific donor
      derived cytotoxic T cells with HLA-A2-restricted recipient minor
      histocompatibility antigens.

PMID- 11597675
TI  - Preterm birth, vascular function, and risk factors for atherosclerosis.
AB  - Low birthweight may predispose to the development of atherosclerosis later in
      life. We have tested the hypothesis that low birthweight as a result of preterm
      birth is associated with reduced flow-mediated endothelial-dependent vasodilation
      (FMD), which is an early stage in the development of atherosclerosis. Mean FMD in
      adolescents born preterm who had a low birthweight did not differ from that for
      controls born at term (0.225 mm vs 0.220 mm, SD 0.1 for both means, p=0.78). Our
      findings indicate that low birthweight attributable to prematurity does not
      increase the risk of vascular disease later in life.

PMID- 11597679
TI  - A molecular mechanism for thrombotic thrombocytopenic purpura.

PMID- 11597676
TI  - Fears that Afghan exodus threatens polio eradication.

PMID- 11597680
TI  - Brain "sensitisation" renders recovering addicts vulnerable to relapse.

PMID- 11597681
TI  - Report finds no link between thimerosal and neurodevelopmental disorders.

PMID- 11597682
TI  - How hibernators might one day solve medical problems.

PMID- 11597683
TI  - US reacts to anxiety about biological attacks.

PMID- 11597684
TI  - Violence against children widespread, says human rights report.

PMID- 11597686
TI  - Japanese official found guilty in HIV-blood trial.

PMID- 11597687
TI  - Canadian doctors' leaders take charge of project to reduce medical error.

PMID- 11597690
TI  - Belgian euthanasia proposal meets resistance.

PMID- 11597691
TI  - Psychologists warn of effects on bereaved children after US terrorist attack.

PMID- 11597692
TI  - Importance of perspective in economic analyses of cancer screening decisions.
AB  - As the fifth, and final, report in this Lancet series on health economics, we
      discuss how economic analyses in public health, with cancer screening as the
      example, differ depending on the perspective taken. We identify nine different,
      but related, decision makers at various levels, from the individual patient to
      society as a whole, and discuss how their different viewpoints affect their
      ultimate decisions. Central to our discussion is the identification of seven
      distinct components of perspective, each potentially important in the screening
      decision. In many fields of healthcare, decisions about the use of resources,
      such as time, wealth, or energy, are made by weighing up the positive and
      negative consequences of the alternatives under consideration and are thus based
      on an economic analysis of the situation (although sometimes this process is
      subconscious). For simplicity, we restrict our report to the effect of
      perspective on cancer screening decisions and show how the costs (negative
      consequences) and benefits (positive consequences) vary depending on the decision
      maker.

PMID- 11597695
TI  - Funding squeeze forces UNHCR cutbacks.

PMID- 11597694
TI  - Neurodegeneration: a failure of neuroregeneration?
AB  - Evidence suggests that the brain, like many other tissues, is in a state of
      dynamic equilibrium. It has an endogenous population of stem cells that
      proliferate in response to environmental and pharmacological manipulations and
      that can replace cells lost in some experimental lesions. However, the fact
      remains that neurodegenerative disorders such as Alzheimer's, Parkinson's, and
      Huntington's diseases are characterised by continuous loss of neurons that are
      not replaced. In this hypothesis, we postulate that a primary deficit in neural
      stem-cell proliferation; migration, or differentiation, or both, might contribute
      to net cell loss and neuronal circuit disruption in these disorders. Experimental
      validation of this hypothesis would not only substantially advance understanding
      of the pathogenesis of these diseases, but could also have profound implications
      for future treatment of these incurable disorders.

PMID- 11597696
TI  - Female genital mutilation in developed countries.

PMID- 11597697
TI  - Tackling female genital cutting in Somalia.

PMID- 11597699
TI  - Human parvovirus B19 and fetal death.

PMID- 11597700
TI  - Human parvovirus B19 and fetal death.

PMID- 11597701
TI  - Warning for antihypertensive drug?

PMID- 11597702
TI  - Systemic lupus erythematosus in African immigrants.

PMID- 11597704
TI  - Medical use of opioids in Bangladesh.

PMID- 11597705
TI  - Health and peace: an opportunity to join forces.

PMID- 11597706
TI  - Health and peace: an opportunity to join forces.

PMID- 11597708
TI  - Antibiotics in preterm labour.

PMID- 11597711
TI  - Vaccinations as risk factors for wheezing disorders.

PMID- 11597712
TI  - Why did the 5th Earl of Derby die?

PMID- 11597713
TI  - Why did the 5th Earl of Derby die?

PMID- 11597714
TI  - Why did the 5th Earl of Derby die?

PMID- 11597715
TI  - 1832 cholera riots.

PMID- 11597716
TI  - Reproducibility of Louis' definition of pneumonia.

PMID- 11597725
TI  - And what is your PSA this lunch time?

PMID- 11597727
TI  - Peripheral blood CD38 expression predicts survival in B-cell chronic lymphocytic
      leukemia.
AB  - CD38 expression was investigated in 161 untreated patients with B-cell chronic
      lymphocytic leukemia (B-CLL). A score system, devised ad hoc by integrating the
      percentage and the mean fluorescence intensity (MFI) values of CD38(+) cells,
      indicated that B-CLL patients with a CD38 score < or =3 are characterized by a
      significantly longer survival compared to those with a CD38 score >3 (P=0.0026).
      Thirty-seven percent of patients with a CD38 score < or =3 and 58% of those with
      a score >3 were dead at 10 years. Multivariate analysis indicates that only the
      CD38 score successfully predicts survival (P=0.0028), with an estimated 3.8-fold
      greater risk of death for those cases with CD38 score >3.

PMID- 11597728
TI  - Re-evaluation of refractory anemia with excess blasts in transformation.
AB  - The category 'refractory anemia with excess blasts in transformation (RAEBt)'
      consists of two sub-sets; one group is categorized based on the percentage of
      blasts in the marrow (> or =20%) and other is based on the percentage of blasts
      in the peripheral blood (> or =5%). We separated RAEBt patients based on these
      two criteria and compared hematologic and clinical relevance to assess the
      reasonable basis for the new classification. All RAEBt patients showing
      peripheral blood (PB) blasts of > or =5% were re-classified as RAEB by the WHO
      classification. This subset of RAEBt patients had lower percentages of bone
      marrow (BM) blasts, and notably they showed frequent complex cytogenetic
      abnormalities, including -5/5q- and/or -7/7q-. Moreover, the RAEBt patients of
      this group had shorter survivals compared to RAEBt patients with BM blasts
      between 20 and 30%. We next assessed hematologic and clinical relevance between
      refractory anemia with excess blasts (RAEB) and RAEBt patients with PB blasts of
      > or =5%. Except for the percentage of blasts in the PB (P=0.0037) and BM
      (P=0.0073), there was no significant difference in hematologic or clinical
      features between RAEB patients with BM blasts of > or =11% and RAEBt patients
      with PB blasts of > or =5%. When MDS patients with PB blasts of > or =5% (RAEBt
      by the FAB classification) were included as RAEB-II based on the "MDS 2000
      classification', there was a high frequency of patients with complex chromosome
      changes, involving 5q and 7q, with significant poorer outcome compared to those
      with RAEB-I. Although it is still controversial whether MDS patients with BM
      blasts 20% or more should be considered as acute leukemia, the utilization of the
      'MDS 2000 classification' might be useful to designate MDS patients diagnosed
      based on the percentage of blasts in the peripheral blood.

PMID- 11597730
TI  - Increased peripheral stem cell pool in MDS: an indication of disease progression?
AB  - The colony-forming capacity of the peripheral blood stem/progenitor cells (PBSC)
      in different forms of myelodysplastic syndrome (MDS) was investigated. In most
      cases of refractory anemia (RA) the colony growth of PBSC was definitely reduced
      as compared to the controls. However, in RA with unfavorable chromosomal
      aberrations, in refractory anemia with ringed sideroblasts (RARS) and in advanced
      stages of MDS such as refractory anemia with excess blasts (RAEB) and refractory
      anemia in transformation (RAEB-t), the number of myeloid progenitor cells
      increased up to 100-fold. In chronic myelomonocytic leukemia (CMML), the increase
      was even more marked, up to 350-fold. Although the number of PBSC was strongly
      elevated, these cells were not able to restore hematopoiesis in vivo. In
      conclusion, the increase of circulating colony-forming cells (CFC) seems to be
      associated with disease progression, and thus, the evaluation of PBSC could be an
      important parameter in the diagnosis of MDS.

PMID- 11597729
TI  - Successful establishment of long-term bone marrow cultures in 103 patients with
      myelodysplastic syndromes.
AB  - We used bone marrow biopsies instead of mononuclear cells to maintain long-term
      cultures from 103 patients belonging to all five sub-categories of
      myelodysplastic syndromes (MDS), as well as 12 normal controls. By week 4, 30-50%
      confluency was reached and could be maintained for up to 12 weeks with 100%
      confluency. The four prominent cells were fibroblasts, macrophages, endothelial
      cells and adipocytes. Immunohistochemical and electron microscopic studies
      provided lineage confirmation. Normal hematopoiesis was well supported by MDS
      stroma. Neither the FAB nor cytogenetics was co-related with the potency of
      growth. MDS stroma appears to be both morphologically and functionally normal.

PMID- 11597731
TI  - Expression of topoisomerase IIalpha in the G0/G1 cell cycle phase of fresh
      leukemic cells.
AB  - Topoisomerase IIalpha (topo IIalpha) is the target enzyme for several
      antineoplastic drugs. Correlation between low expression of topo IIalpha and drug
      resistance has been shown in vitro, but there is limited evidence of a
      correlation to initial response to treatment or to overall prognosis. Normal
      cells express topo IIalpha in S/G2/M phase of the cell cycle but not in G0/G1
      phase. However, some data suggest that topo IIalpha could be expressed in G0/G1
      phase in malignant cells. We have investigated the expression of topo IIalpha in
      leukemic cells from 25 patients with acute leukemia by flow cytometry, separating
      cells of different cell cycle phases. We demonstrated that 9/25 samples showed
      >50% positive cells in G0/G1, and another five samples showed >20%. This finding
      could possibly provide an explanation to previous difficulties in correlating
      topo IIalpha expression with clinical outcome. Six of eight patients, where >20%
      of the cells in G0/G1 were positive for topo IIalpha, entered CR, compared to one
      of five patients with <20% topo IIalpha positive cells in G0/G1. We suggest that
      topo IIalpha expression in G0/G1 in leukemic cells may be of predictive value for
      clinical response to cytostatic drugs.

PMID- 11597732
TI  - Upstream mediators of the Fas apoptotic transduction pathway are defective in B
      chronic lymphocytic leukemia.
AB  - Data concerning the presence and the functionality of Fas receptor in malignant B
      cells are controversial. We have analyzed Fas molecules on B-cells from patients
      with B-chronic lymphocytic leukemia (B-CLL) cells. We observed a large
      variability, both of percentage of Fas-positive cells and of intensity of Fas
      level. Fas triggering was inefficient in inducing apoptosis whatever the number
      of Fas-positive B-cells, the amount of Fas receptors. B-cells were also resistant
      to etoposide treatment, but able to undergo apoptosis after dexamethasone
      treatment. We suggest that the Fas apoptotic pathway is altered in B-CLL patients
      at the initial step(s) of apoptotic machinery.

PMID- 11597733
TI  - DNase I hypersensitivity analysis of the human CCAAT enhancer binding protein
      epsilon (C/EBPepsilon) gene.
AB  - Human C/EBPepsilon is a recently cloned member of the C/EBP family of
      transcriptional factors. Previous studies demonstrated that the expression of
      this gene is tightly regulated in a tissue-specific manner; it is expressed
      almost exclusively in myeloid cells. To understand the mechanism by which the
      expression of C/EBPepsilon gene is controlled, we cloned a large genomic region
      surrounding the C/EBPepsilon gene and performed a DNase I hypersensitivity
      analysis of this locus. These sites probably represent areas of binding of
      proteins modulating gene transcription. Hypersensitive (HS) regions in 30 kb of
      DNA surrounding the C/EBPepsilon gene were examined in C/EBPepsilon high
      expressing (NB4, HL-60), low-expressing (Jurkat), very-low-expressing (KG-1), and
      non-expressing (K562) hematopoietic cells as well as in non-hematopoietic-non
      expressing cells (MCF-7, DU 145, PC-3). Three HS sites were detected near the
      first exon of C/EBPepsilon gene. They were found only in hematopoietic cells and
      were especially prominent in C/EBPepsilon expressing cells, suggesting that these
      sites play an important role in transcribing the gene. These hypersensitive bands
      did not change when the cells were cultured with retinoids. Gel-shift assays
      using 200 bp of nucleotide sequences that encompassed the hypersensitive sites
      and nuclear extracts from NB4 and Jurkat cells (C/EBPepsilon expressing) as well
      as K562 and MCF-7 cells (non-expressing) showed different retarded bands on gel
      electrophoresis. A fourth HS site, located about 11 kb upstream of exon 1, was
      found only in cells highly expressing C/EBPepsilon. Two sites, one about 4.5 kb
      upstream of exon 1 and another about 8.5 kb downstream of exon 2, were positive
      only in non-expressing cell lines, suggesting that repressors may bind in these
      areas. Taken together, we have found six specific DNase I hypersensitive sites in
      the region of C/EBPepsilon that may be involved in regulating transcription of
      this gene.

PMID- 11597734
TI  - Progenitor cells from patients with advanced phase chronic myeloid leukaemia
      respond to STI571 in vitro and in vivo.
AB  - STI571 targets p210(BCR-ABL) in chronic myeloid leukaemia (CML). In vitro, STI571
      reduces self-replication (replating ability) by chronic-phase CML CFU-GM. Here,
      we studied CFU-GM in advanced-phase (accelerated and blast crisis) CML. The
      numbers and self-replication of CFU-GM in advanced phase were greater than in the
      chronic phase. Self-replication by CFU-GM from advanced phase patients was
      reduced by STI571 or IFN alfa to the same extent as in the chronic phase. The
      reduced replating ability induced by STI571 correlated with that induced by IFN
      alpha (r=0.73). STI571 treatment in vivo also reduced replating ability and the
      numbers of CFU-GM/ml of blood.

PMID- 11597735
TI  - Homotypic interactions protect chronic lymphocytic leukaemia cells from
      spontaneous death in vitro.
AB  - Chronic lymphocytic leukaemia (CLL) cells are long-lived in vivo but undergo
      spontaneous apoptosis when cultured in vitro. Since CLL cells associate
      intimately with one another at sites of tissue involvement, we examined the
      hitherto unproven possibility that homotypic interactions between the malignant
      cells might reduce their propensity to undergo spontaneous cell death. In a
      series of experiments in which highly pure CLL-cell populations were cultured on
      a non-adherent surface, cell viability was found to increase markedly with the
      level of crowding at the bottom of the culture vessel. The effect was observed
      among unevenly distributed cells within a single culture vessel and did not
      require direct cell-cell contact. This indicates that cell survival was being
      regulated in an autocrine fashion by locally acting soluble products. Conditioned
      medium from crowded CLL cells enhanced the survival of autologous non-crowded
      cells, indicating that at least some of the autocrine survival factors produced
      by CLL cells could accumulate in the extracellular environment. In addition, the
      survival of non-crowded CLL cells was markedly enhanced by co-culturing them with
      an excess of autologous fixed cells. This protective effect of direct cell-cell
      contact was mediated by specific surface structures since it was abrogated by pre
      treating the fixed cells with neuraminidase. Our results provide the first direct
      demonstration that the survival of cultured CLL cells is enhanced by homotypic
      interactions. We speculate that these protective effects may contribute to the
      accumulation of CLL cells in vivo, and that further elucidation of the underlying
      mechanisms may lead to novel therapeutic strategies.

PMID- 11597736
TI  - Second International Symposium on myelodysplastic syndrome in childhood,
      Hindsgavl castle, Fyn, Denmark, May 11-14, 2000.

PMID- 11597737
TI  - Cerebellar granulocytic sarcoma in an infant with CD56+ acute monoblastic
      leukemia.
AB  - Granulocytic sarcoma (GS) is a form of extramedullary leukaemia (EML). The
      presence of the neural cell adhesion molecule (NCAM) on the surface of the
      blasts, which is recognized by the CD56 monoclonal antibody, enhances their
      propensity for tissue penetration. GS within the central nervous system (CNS), in
      particular within the cerebellum, is extremely uncommon. We review the literature
      and describe an infant with isolated cerebellar GS relapse, which antedated a
      CD56+ acute monoblastic leukaemia bone marrow (BM) relapse.

PMID- 11597738
TI  - Dysgranulopoiesis, low blast count and t(8;21): an unusual presentation of
      t(8;21) AML according to the WHO classification: a pediatric experience.

PMID- 11597739
TI  - Life and death of ALL cells in the milieu of bone marrow stroma.

PMID- 11597740
TI  - The leukemic effect of anticholinesterases.

PMID- 11597741
TI  - Murine lymphomas: are there counterparts in the revised European-American
      classification of lymphoid neoplasms?

PMID- 11597743
TI  - The small extracellular loop of CD81 is necessary for optimal surface expression
      of the large loop, a putative HCV receptor.
AB  - Human tetraspanin CD81 is a putative receptor for hepatitis C virus (HCV),
      because it has been shown to bind 'bona fide' HCV particles. CD81, as all
      tetraspanins, spans the membrane four times forming two extracellular loops: a
      small (SEL) and a large one (LEL). We have shown previously that a recombinant
      form of LEL is sufficient for binding HCV through the major envelope glycoprotein
      E2. The role of SEL in the CD81-HCV interaction was questioned. We found that
      transfectants expressing LEL alone bind the recombinant HCV-E2 protein at much
      lower levels than cells expressing the wild type CD81. And therefore whether SEL
      contributes to the CD81-HCV interaction or whether it influences the expression
      of LEL was examined. We have found that in the absence of SEL, LEL is expressed
      at significantly reduced levels on the cell surface because it is retained
      intracellularly, while HCV-E2 still binds LEL. Our data suggest that SEL of CD81
      does not mediate interaction with HCV, but contributes to optimal cell surface
      expression of LEL by mediating translocation of the whole CD81 molecule to the
      cell surface.

PMID- 11597745
TI  - Expression kinetics of the transcript and product of the UL28 homologue of bovine
      herpesvirus 1.
AB  - We report that the bovine herpesvirus 1 (BHV1) UL28 ORF, a homologue of the
      herpes simplex virus (HSV) UL28 gene, represents a functional gene encoding a
      viral specific protein. The BHV1 UL28 ORF, located at positions 53058-->55538 of
      the viral genome, encodes a viral specific transcript of 3.4 kb detected at 6 h
      post-infection (p.i.) after which its levels accumulated up to 12 h p.i. and then
      remained constant up to 24 h p.i. Transcription of the BHV1 UL28 was determined
      to initiate 95 bases upstream from the ORF's initiating codon, which corresponds
      to 33 nucleotides downstream from a putative TATA box. A BHV1 UL28 specific
      antiserum, generated against a T7-Tag/UL28 fusion protein expressed in E. coli,
      specifically reacted with a 100 kDa protein in Western blots of BHV1-infected
      protein cell lysates. The expression kinetics of the protein was delayed by 6 h
      relative to that of its transcript suggesting that the gene is regulated at the
      translational level. In contrast to the HSV and pseudorabies virus UL28 genes,
      which belong to viral genes of the early (beta) class, that of BHV1 was
      unambiguously classified as a gamma2 gene. Further studies will be required to
      determine whether these kinetic differences have any functional implications.

PMID- 11597744
TI  - Molecular characterisation of the nucleocapsid protein gene, glycoprotein gene
      and gene junctions of rhabdovirus 903/87, a novel fish pathogenic rhabdovirus.
AB  - The sequences of the nucleocapsid and glycoprotein genes and the gene junctions
      of the fish pathogenic rhabdovirus 903/87 were determined from cDNA and PCR
      clones. The mRNA of the nucleocapsid is most likely 1492 nucleotides long and
      encodes a protein of 426 amino acids, whereas the mRNA of the glycoprotein is
      likely to be 1682 nucleotides long and the protein 517 amino acids. When the
      nucleocapsid and glycoprotein genes of virus 903/87 were compared at amino acid
      level with other rhabdoviruses they showed the highest homology with the
      Vesiculovirus genus. By sequencing the junctions between the N, P, M, G and L
      genes it was determined that transcription start and stop codons were conserved
      between virus 903/87 and the vesiculoviruses. Virus 903/87 has no open reading
      frame coding for a non-virion gene between the glycoprotein and the polymerase
      gene. Phylogenetic studies based on rhabdovirus nucleocapsid and glycoprotein
      genes suggested that virus 903/87 is related to viruses in the Vesiculovirus
      genus.

PMID- 11597746
TI  - Origin and evolution of Georgia 98 (GA98), a new serotype of avian infectious
      bronchitis virus.
AB  - We previously identified GA98, a new serotype of infectious bronchitis virus
      (IBV), which is closely related to the DE072 serotype of IBV genetically, but not
      antigenically. Herein, we analyzed the 421bp sequence of a hypervariable region
      (HVR) (position 114-534, counting from the ATG start site) of the S1 subunit of
      GA98 IBVs to further examine the evolution of these viruses. These viruses were
      isolated between the years 1997 and 2000. Phylogenetic analysis of the deduced
      amino acid sequence on that region indicated that GA98 isolates from different
      regions of Georgia were the result of a single introduction of the S1 gene of the
      DE072 serotype progenitor. Most of the mutations were nonsynonymous and had
      become fixed in a progressive manner. The evolutionary and mutation rates in the
      HVR was calculated as 2.5 and 1.5% per year, respectively. This new serotype of
      IBV appears to be evolving very fast compared with other serotypes of IBV. We
      further determined the complete coding sequence of the S1 gene of seven isolates
      obtained from one selected region in North Georgia. Together with virus
      neutralization data, it appears that GA98 arose from immune selection caused by
      DE072 vaccine use. Reasons for this conclusion are discussed.

PMID- 11597747
TI  - The partial purified RNA-dependent RNA polymerases from bamboo mosaic potexvirus
      and potato virus X infected plants containing the template-dependent activities.
AB  - RNA-dependent RNA polymerases (RdRp) isolated from bamboo mosaic potexvirus
      (BaMV) and potato virus X infected Nicotiana benthamiana plants and solubilized
      with the detergent NP-40, generated a full-length genomic and two subgenomic
      double-stranded RNAs of respective viruses in an in vitro RdRp assay containing
      endogenous RNA templates. Template-dependent and species-specific RdRp activity
      could be detected after the removal of endogenous RNA templates. The 3'
      untranslated regions (UTR) containing a stretch of 40 adenylate residues were
      shown to be an efficient exogenous RNA template for in vitro RdRp reactions.
      Solution hybridization and nuclease digestion studies revealed that the products
      transcribed in vitro were minus-sense. Besides using the 3' UTR for minus-sense
      RNA synthesis, the BaMV RdRp can also recognize 3' terminal 77 nucleotides of the
      minus-strand for plus-sense RNA synthesis. Promoter studies with BaMV RdRp showed
      that domain D containing the potexviral hexamer motif of the 3' UTR would be the
      major contributor of minus-sense RNA synthesis in vitro. On the other hand, the
      pseudoknot domain containing the poly(A) sequences would be sufficient for minus
      sense RNA synthesis.

PMID- 11597748
TI  - Caspase-3-like proteases are activated by infection but are not required for
      replication of vesicular stomatitis virus.
AB  - Infection with vesicular stomatitis virus (VSV), the prototype rhabdovirus,
      causes apoptotic DNA fragmentation, but the role of apoptosis in the VSV-host
      interaction remains unclear. Apoptosis is the gene-regulated mechanism triggered
      by a wide variety of stimuli that lead to cell death in a choreographed manner.
      In the present study, infection of the Jurkat T cell line with VSV led to
      activation of caspase-3 and caspase-7, with subsequent apoptotic events involving
      poly (ADP ribose) polymerase (PARP) cleavage, DNA fragmentation, and membrane
      damage. Caspase activation was correlated with viral protein expression
      suggesting a link between viral replication and apoptosis. We hypothesized that
      VSV replication might depend on apoptosis and that the inhibition of apoptosis
      would lead to significant decreases in viral titers. When various inhibitors of
      apoptosis in VSV-infected cells were used, PARP cleavage and DNA fragmentation
      were inhibited but the production of infectious progeny was not affected. In
      addition, we demonstrated that the activation of caspase-3-like proteases is
      required for VSV-induced apoptosis but not in vitro viral replication. Apoptosis
      following VSV infection is likely to be either a host-cell attempt to control
      viral replication or may be a ploy used by the virus to facilitate its in vivo
      replication and spread.

PMID- 11597749
TI  - Identification and molecular characterization of 18 paramyxoviruses isolated from
      snakes.
AB  - Viral agents from 18 different snake species (families Colubridae, Viperidae, and
      Crotalidae) showing respiratory symptoms and neuronal disease were identified as
      paramyxoviruses by typical cytopathogenic effect (CPE), electron microscopy, and
      hemagglutination inhibition. Detailed molecular characterization of the viruses
      was performed by partial L- and F-gene-specific reverse transcription polymerase
      chain reaction (RT-PCR) and sequencing, nucleotide and amino acid sequence
      alignment, and phylogenetic analysis (PHYLIP). RT-PCR of the partial L-gene (566
      nt) was successful for all 18 viruses; amplicons of the partial F-gene (918 nt)
      could be obtained in 16 cases. F- and L-sequence alignment revealed similarities
      to Fer de Lance virus (FDLV) ranging from 79 to 88% on a nucleotide basis, and 94
      to 99% on an amino acid basis. Phylogenetic analysis of the ophidian
      paramyxoviruses resulted in three clusters for the L-gene sequence and
      corresponding clusters for the F-gene sequence, indicating no species
      specificity. We analyzed the F-protein of the snake paramyxoviruses, which proved
      to have an identical conserved motif of heptad repeat A and predicted a furin
      cleavage site. This uniformity distinguishes the snake virus group from the other
      type species of the subfamily Paramyxovirinae. For further classification, we
      aligned the sequences of the ophidian paramyxoviruses and members of the
      Paramyxoviridae, such as Sendai virus (genus Respirovirus), mumps virus (genus
      Rubulavirus), measles virus (genus Morbillivirus), human respiratory syncytial
      virus (genus Pneumovirus) (Van Regenmortel and 10 co-authors, 2000) and Hendra
      virus, which have recently been suggested as type species of the genus
      Henipavirus (Wang et al., 2000). Maximum sequence similarity was found to the
      partial L-gene of Sendai virus, with 56% nucleotide and 61% amino acid identity.
      The FDLV and Sendai virus cluster in the phylogenetic analysis of L- and F
      protein regarding the Paramyxovirus type species and Hendra virus and show the
      closest relationship. Regarding the biological properties, the antigenic
      distance, and particularly the low homology of available sequences, we propose a
      new genus for the reptilian paramyxoviruses within the Paramyxoviridae.

PMID- 11597750
TI  - DNA mediated immunization with encoding the nucleoprotein gene of porcine
      transmissible gastroenteritis virus.
AB  - The immune response to a naked plasmid DNA encoding the nucleoprotein (N protein)
      of porcine transmissible gastroenteritis virus (TGEV) was investigated in this
      study. A complementary DNA of the entire N gene was amplified by RT-PCR, and
      inserted into a mammalian expression vector (pcDNA3.1) to construct a recombinant
      plasmid (pcDNA/N). To evaluate the immunogenicity of the construct, BALB/c mice
      were intramuscularly immunized with different doses (50, 100 and 200
      microg/mouse) of pcDNA/N twice at a 5-week interval. An optimal antibody response
      was achieved with 100 microg of pcDNA/N. The response lasted at least 11 weeks
      after primary immunization. By western blotting analysis, the antibodies
      specifically recognized a 47 kDa protein corresponding to the viral N protein,
      but they did not reveal neutralizing activity against infectious TGEV in vitro.
      Immunoglobulin G2a was predominant among these antibodies, which was indicative
      of Th1 type cell activation in pcDNA/N immunized mice. Moreover, spleen cells
      from these mice showed stronger immune responses than those from live vaccine or
      parental vector immunized mice. These results suggest that the construct can
      elicit both humoral and cell-mediated immune (CMI) responses against TGEV N
      protein in mice.

PMID- 11597753
TI  - Molecular typing of echovirus serotype 4 isolates.
AB  - We report on clinical samples Stuttgart/97, Berlin/99 and Jasi/99 associated with
      aseptic meningitis. All three samples contained echovirus 4 (E4) but Stuttgart/97
      was simultaneous infected with echovirus 30 (E30). The genetic relationship of
      the E4 strains was assessed using RT-PCR and direct sequencing of amplicons
      derived from the genomic region encoding the capsid protein VP1. The sequences
      have been compared with each other and with sequences of further E4 strains
      obtained from GenBank. The analysis confirms that sequences of recent isolates
      have drifted away from elderly strains over a longer period of time. Several
      amino acid changes in assumed antigenic sites of the VP1 gene may be sufficient
      to cause changes in antigenic specificity and therefore they may be a reason for
      failure of serological typing of some new antigenic E4 variants.

PMID- 11597754
TI  - Detection of equine herpesvirus type 2 (EHV-2) in horses with
      keratoconjunctivitis.
AB  - The prevalence of EHV-2 in 27 horses with keratoconjunctivitis and 21 clinically
      healthy horses of different ages and stocks were analyzed. We demonstrated that
      EHV-2 was present in 12 keratoconjunctivitis cases as shown by nested PCR on
      ocular swabs. This is statistically more often than in the control group, where
      only two ocular swabs were EHV-2 positive. Cocultivation was successful on
      peripheral blood leukocytes of healthy and diseased horses but not on swabs. We
      isolated ten EHV-2 strains from diseased and nine from control horses, whereas 16
      isolates showed different restriction enzyme patterns. The results of
      immunfluorescence and neutralization tests are predictory only in combination
      with the nested PCR data on ocular swabs. A successful antiviral treatment in
      nine out of 16 cases supports the aetiological role of EHV-2 in this ocular
      disease.

PMID- 11597755
TI  - Virulence of swine vesicular disease virus is determined at two amino acids in
      capsid protein VP1 and 2A protease.
AB  - To identify the genetic determinants of virulence for swine vesicular disease
      virus, a panel of recombinant and site-directed mutant viruses were constructed
      from cDNA clones of a virulent J1'73 strain and an avirulent H/3'76 strain.
      Initial studies mapped the genetic determinants of virulence to either or both of
      the two sites at nucleotide (nt) 2842, encoding VP1-132, and nt 3355, encoding 2A
      20. To determine their relative importance with regard to virulence, viruses
      mutated at either of these two sites from the avirulent to the virulent genotype
      and vice versa were tested in pigs. Viruses, mutated at nt 2842 to the virulent
      genotype (vSVLS104MJ1) or mutated at nt 3355 to the virulent genotype
      (vSVLS201MJ1), slightly recovered virulence but were very weak compared with
      viruses with site-directed mutations at both sites (vSVLS104/201MJ1). On the
      other hand, viruses, mutated at nt 2842 to the avirulent genotype (vSVLS104M00)
      or mutated at nt 3355 to the avirulent genotype (vSVLS201M00), did not have
      attenuated virulence. Sequence analysis of viruses recovered from inoculated pigs
      revealed that reversion at nt 3355 to the virulent genotype occurred in pigs
      which had been inoculated with vSVLS201M00. These results suggested that both
      amino acids determined the virulent phenotype, but that the 2A-20 site might be
      the major determinant for virulence.

PMID- 11597756
TI  - Hypervariable genes in Grapevine leafroll associated virus 1.
AB  - Analysis of nucleotide sequences of 10 open reading frames from the Grapevine
      leafroll associated virus 1 (GLRaV-1), a tentative member of the genus
      Closterovirus, revealed the presence of an unusually high degree of sequence
      variation in ORFs 3, 6 and 7 encoding a homologue of heat shock protein 70 and
      two diverged copies of the coat protein (CPd1 and CPd2), respectively. Overall,
      75 clones corresponding to ORFs 3, 6 and 7 were sequenced and 1916 nucleotide
      changes were recorded relative to the published sequence. Surprisingly, none of
      the changes resulted in a frame shift or stop codon and there was a trend for the
      conservation of amino acids or change to amino acids having similar
      physiochemical properties. The CPd2 gene was particularly variable with a
      mutation seen in 60% of the nucleotide positions in one or more of the 1.1-kb
      cDNA clones sequenced. These observations suggest that GLRaV-1 may exist in the
      form of a heterogeneous population, possibly resulting from the lack of selective
      pressure and from mixing of virus strains due to viticulture practices of
      vegetative propagation and grafting over the centuries.

PMID- 11597757
TI  - Symposium on Marburg and Ebola viruses.

PMID- 11597759
TI  - Thyroid hormone regulation of rhes, a novel Ras homolog gene expressed in the
      striatum.
AB  - Thyroid hormone action on brain development is essentially exerted through
      regulation of the expression rate of a number of genes some of which have been
      identified in the past 10 years. In the present work we describe the thyroid
      hormone regulation of a novel Ras homolog which we have named Rhes (Ras homolog
      enriched in striatum). The rhes cDNA was previously isolated in subtractive
      hybridization experiments aimed at identifying cDNA clones corresponding to genes
      expressed preferentially in the rat striatum. The sequence was found to encode a
      small GTP-binding protein of the Ras family with highest homology to the
      dexamethasone-inducible Dexras1. Here we show that rhes mRNA and protein in the
      striatum are strongly dependent on the thyroidal status. Developmentally, Rhes
      was regulated such that in normal rats there was an increased rhes mRNA content
      in the striatum after postnatal day 5 (P5). Rhes concentration in hypothyroid
      rats was similar to that of normal rats at P5, but the subsequent age-dependent
      increase was blunted. The administration of a single T3 dose to hypothyroid rats
      normalized rhes mRNA concentration in 8 h, whereas it took 24 h, or more, to
      normalize the expression of rc3, another T3-dependent brain gene, involved in PKC
      signaling. Double in situ hybridization using rhes and rc3 riboprobes showed that
      the bulk of rhes signal was located in cells expressing rc3. Given the relevance
      of small GTPases in signal transduction it is very likely that control of rhes,
      in addition to rc3, is of relevance to explain the actions of thyroid hormone in
      the striatum, a region of the brain especially vulnerable in neurological
      cretinism.

PMID- 11597760
TI  - Evidence for a role for GABA(A) and NMDA receptors in ethanol inhibition of long
      term potentiation.
AB  - We have investigated the mechanisms by which acute ethanol inhibits the induction
      of long-term potentiation (LTP) in area CA1 of the rat hippocampal slice. In a
      previous report [Alcohol. Clin. Exp. Res. 21 (1997) 404] we demonstrated that
      ethanol produces only a modest inhibition of pharmacologically isolated N-methyl
      D-aspartate receptors (NMDAR) in the CA1 region of the hippocampus. Moreover,
      this level of inhibition was not sufficient to account for ethanol's complete
      inhibition of LTP induction in this brain region. One possible explanation of
      these results is that we may have underestimated ethanol's ultimate effect on the
      NMDAR by focusing on pharmacologically isolated NMDAR responses. Ethanol might
      indirectly inhibit the NMDAR by, for example, potentiating the GABA(A)R. To
      explore this possibility, we first examined the effects of the GABA(A)R
      antagonist picrotoxin (PTX) and the allosteric GABA(A)R modulator flunitrazepam
      on NMDAR responses. We demonstrate that these modulators of GABA(A)R activity
      significantly affect the magnitude of synaptically evoked NMDAR responses. We
      next examined the effects of ethanol on NMDAR responses in the presence and
      absence of PTX. We see a significantly greater ethanol inhibition of the NMDAR
      when GABA(A)Rs are functional, i.e. in the absence of PTX. These data suggest
      that ethanol produces an inhibition of the NMDAR indirectly by affecting the
      GABA(A)R neurotransmission. Moreover, we found that ethanol inhibition of NMDAR
      activity, both directly through actions on the NMDAR, and indirectly, possibly
      through potentiation of GABA(A)R activity, is sufficient to account for ethanol's
      complete blockade of LTP induction.

PMID- 11597761
TI  - Phosphorylated cAMP response element binding protein in the mouse brain after
      fear conditioning: relationship to Fos production.
AB  - Phosphorylation of the cAMP response element binding protein (pCREB) triggered by
      associative learning was monitored immunohistochemically in different areas of
      the mouse brain during a 6-h interval, starting immediately after training. One
      trial context-dependent fear conditioning was employed as a learning paradigm.
      Training consisted of contextual exposure followed by shock. Control groups
      consisted of naive mice, mice exposed to the context alone and mice exposed to an
      immediate shock in the context. For all trained mice, the time course of CREB
      phosphorylation in hippocampus, parietal cortex and amygdaloid nuclei exhibited a
      biphasic pattern. The early phase was between 0 and 30 min, and the late phase
      was between 3 and 6 h after training. The animals exposed to context followed by
      an electric shock, as well as those exposed to an immediate electric shock,
      exhibited significantly higher pCREB levels than the mice subjected to context
      alone. During the late phase, the pCREB levels were highest in the mice exposed
      to the context followed by shock. It was observed that CREB phosphorylation and
      Fos production followed different regional and stimulus-dependent patterns. It is
      suggested that the early phase of pCREB increase may be related to stress-related
      behaviors, whereas the late phase may rather relate to memory consolidation.

PMID- 11597762
TI  - Caspase-3 activation and DNA fragmentation in primary hippocampal neurons
      following glutamate excitotoxicity.
AB  - Excitotoxic glutamate CNS stimulation can result in neuronal cell death.
      Contributing mechanisms and markers of cell death are the activation of caspase-3
      and DNA fragmentation. It remains to be resolved to which extent both cellular
      reactions overlap and/or indicate different processes of neurodegeneration. In
      this study, mixed neuronal cultures from newborn mice pubs (0-24 h) were
      stimulated with glutamate, and the co-localization of active caspase-3 and DNA
      fragmentation was investigated by immunocytochemistry and the TUNEL nick-end
      labelling. In untreated cultures, 8% scattered neurons (marked by MAP-2)
      displayed activated caspase-3 at different morphological stages of degeneration.
      TUNEL staining was detected in 5% of cell nuclei including GFAP-positive
      astrocytes. However, co-localization of active caspase-3 with TUNEL was less than
      2%. After glutamate stimulation (125 microM), the majority of neurons was dying
      between 12 and 24 h. The absolute number of active caspase-3 neurons increased
      only moderately but in relation of surviving neurons after 24 h from 8 to 36%
      (125 microM), to 53% (250 microM) or to 32% (500 microM). TUNEL staining also
      increased after 24 h following glutamate treatment to 37% but the co-localization
      with active caspase-3 remained at the basal low level of 2%. In our system,
      glutamate-mediated excitotoxicity effects the DNA fragmentation and caspase-3
      activation. Co-localization of both parameters, however, is very poor. Active
      caspase-3 in the absence of TUNEL indicates a dynamic degenerative process,
      whereas TUNEL marks the end stage of severe irreversible cell damage regardless
      to the origin of the cell.

PMID- 11597763
TI  - Genomic organization and neuronal cell type specific promoter activity of beta
      isoform of Ca(2+)/calmodulin dependent protein kinase II of rat brain.
AB  - The gene encoding the beta isoform of rat Ca(2+)/calmodulin-dependent protein
      kinase II was cloned, and its exon-intron organization was analyzed. The gene
      consisted of 21 exons spanning more than 80 kilobase pairs and the coding
      sequence was made up of 20 exons. Each discrete functional unit, such as the ATP
      binding site, the autophosphorylation site responsible for Ca(2+)-independent
      activity, the calmodulin binding site, and the link structure, was encoded by a
      single exon. All splice junction sequences flanking the introns conformed to the
      consensus splice junction sequence and the GT-AG splice rule. The site of
      transcription initiation was -78 bases from the initiation codon as determined by
      5' RACE analysis. The promoter activity of the gene was analyzed using
      neuroblastomas, as well as non-neuronal cell lines. Neuronal cell type-specific
      promoter activity was found in the 5'-upstream region -66 to -35 bp from the
      transcription initiation site. Silence elements were found further upstream at 
      222 to -123 bp and -576 to -323 bp. A protein bound to the -66 to -35 region was
      found in the nuclear extract of rat brain, including the cerebellum, forebrain,
      and brainstem, by gel mobility shift assay.

PMID- 11597764
TI  - Differential expression of active, phosphorylation-dependent MAP kinases,
      MAPK/ERK, SAPK/JNK and p38, and specific transcription factor substrates
      following quinolinic acid excitotoxicity in the rat.
AB  - Excitotoxicity is considered a major cell death inductor in neurodegeneration.
      Yet mechanisms involved in cell death and cell survival following excitotoxic
      insults are poorly understood. Expression of active, phosphorylation-dependent
      mitogen-activated extracellular signal-regulated kinases (MAPK/ERKs), stress
      activated c-Jun N-terminal kinases (SAPK/JNKs) and p38 kinases, as well as their
      putative active specific transcriptional factor substrates CREB, Elk-1, ATF-2, c
      Myc and c-Jun, have been examined following intracortical injection of the
      glutamate analogue quinolinic acid (QA). Increased JNK(P) and p38(P)
      immunoreactivity has been found in the core at 1 h following QA injection,
      whereas increased MAPK(P) immunoreactivity occurs in neurons and glial cells
      localised around the lesion and in neurons in remote cortical regions. This is
      accompanied by strong phosphorylated Ser63 c-Jun (c-Jun(P)) immunoreactivity in
      the core at 3 h, and by strong phosphorylated CREB, Elk-1 and ATF-2 (CREB(P), Elk
      1(P) and ATF-2(P)) immunoreactivity mainly in neurons around the core at 24 h
      following QA injection. Examination with the method of in situ end-labelling of
      nuclear DNA fragmentation has revealed large numbers of positive cells with no
      apoptotic morphology in the core at 24 h, thus indicating that JNK(P), p38(P) and
      c-Jun(P) over-expression precedes cell death. In contrast, MAPK(P), CREB(P), Elk
      1(P) and ATF-2(P), but not phosphorylated c-Myc (c-Myc(P)), over-expression
      correlates with cell survival. Examination of cleaved, active caspase-3 has shown
      specific immunoreactivity restricted to a few hematogenous cells in the area of
      injection. Since cleaved caspase-3 is not expressed by dying cells in the present
      paradigm, JNK(P), p38(P) and c-Jun(P) expression is not associated with caspase-3
      activation. The present results demonstrate selective activation of specific MAPK
      signals which are involved either in cell death or cell survival triggered by
      excitotoxic insult.

PMID- 11597765
TI  - Involvement of VIP on BDNF-induced somatostatin gene expression in cultured fetal
      rat cerebral cortical cells.
AB  - Previous studies have shown that BDNF promotes expression of SS. In earlier
      studies we demonstrated the stimulatory effect of locally produced VIP upon SS
      secretion. These facts led us to explore the peptidergic action of BDNF on VIP,
      and to determine if BDNF-induced SS might be mediated by the induction of VIP.
      Cultured fetal rat cerebrocortical cells were incubated with BDNF (50 ng/ml)
      and/or VIP (10(-11) M) for 2 and 5 days. In other experiments IgGs from BDNF or
      VIP antisera were also added. BDNF increased VIP and SS gene expression and
      peptide production. After 2 days of incubation with both BDNF and VIP the
      induction of SS mRNA was similar to that obtained with BDNF alone. However when
      the treatment was extended to 5 days the increase in SS mRNA was higher than that
      obtained with BDNF alone. This finding suggests the possibility that both factors
      acted synergistically. To define the potential role of VIP in the response of SS
      gene expression to BDNF, endogenous VIP was blocked with IgGs from VIP antiserum.
      Under these experimental conditions BDNF-induced SS decreased. Our study provides
      the first evidence that BDNF up-regulates VIP gene expression and concentration
      of the peptide. The involvement of VIP on BDNF-induced SS gene expression is also
      demonstrated.

PMID- 11597766
TI  - Multiple transcripts generated by the DCAMKL gene are expressed in the rat
      hippocampus.
AB  - We have recently cloned a novel Doublecortin CaMK-like kinase (rDCAMKL) cDNA, and
      a related cDNA called CaMK-related peptide (CARP) from the rat hippocampus. These
      genes are structurally highly similar to the human DCAMKL-1 gene and
      doublecortin, a gene associated with X-linked lissencephaly and subcortical band
      heterotopia. Here we report on the genomic organization of the murine DCAMKL gene
      and its products. Our results show that DCAMKL and CARP are alternative splice
      products of the same gene. The DCAMKL gene also generates three alternatively
      spliced rDCAMKL transcripts of which we have cloned the corresponding cDNAs and
      which potentially generate different DCAMKL proteins. In situ hybridization
      experiments show that the different rDCAMKL transcripts are all expressed in the
      adult rat hippocampus. We conclude that alternative splicing of the DCAMKL gene
      may generate different but similar proteins in the adult rat hippocampus thereby
      regulating different but overlapping aspects of DCAMKL controlled neuronal
      plasticity.

PMID- 11597768
TI  - Identification of three novel non-classical cadherin genes through comprehensive
      analysis of large cDNAs.
AB  - The terminal sequences of long cDNAs from human brains were subjected to an
      improved method of motif-trap screening. This process resulted in the
      identification of three novel genes that encode proteins with 27, 27, and six
      cadherin domains that we denoted as KIAA1773, KIAA1774 and KIAA1775,
      respectively. Sequence analysis indicated that the products of these genes were
      non-classical cadherins. KIAA1773 was found to be a mammalian homologue of the
      Drosophila dachsous gene but the remaining two genes did not have any likely
      homologues in public databases. Assessment of their expression in rat tissues
      indicated that these genes are expressed in highly distinct and tissue-specific
      patterns. Notably, KIAA1775 is expressed almost exclusively in the olfactory bulb
      in the rat brain. In situ hybridization further showed that KIAA1775 is strongly
      expressed by the mitral and tufted cells in the main and accessory olfactory
      bulbs, suggesting that KIAA1775 may be important in the formation and maintenance
      of neuronal networks, particularly those in the olfactory bulb. This study
      clearly shows the importance and usefulness of our cDNA project in search for
      genes encoding large proteins, as this project has allowed us to identify several
      novel non-classical cadherin genes that have thus far not been detected by
      conventional methods.

PMID- 11597767
TI  - Group I metabotropic glutamate receptor activation increases phosphorylation of
      cAMP response element-binding protein, Elk-1, and extracellular signal-regulated
      kinases in rat dorsal striatum.
AB  - Cyclic AMP response element-binding protein (CREB) is a major transcriptional
      activator at the calcium and cAMP response-element (CaCRE). Phosphorylated
      (p)CREB facilitates gene expression in striatal neurons. Elk-1 is another
      transcriptional regulator at the serum response element in the upstream promoter
      region of the CaCRE. Elk-1 is phosphorylated by extracellular signal-regulated
      kinases (ERK) and may also contribute to the regulation of gene expression. To
      evaluate putative roles of group I metabotropic glutamate receptors (mGluRs) in
      CREB, Elk-1, and ERK phosphorylation, the group I selective agonist, 3,5
      dihydroxyphenylglycine (DHPG), was infused into the dorsal striatum at doses of
      125, 250, or 500 nmol in freely moving rats. Semi-quantitative
      immunohistochemistry demonstrated that DHPG significantly increased levels of
      pCREB, pElk-1, and pERK immunoreactivity of ipsilateral dorsal striatum in a dose
      dependent manner. The increased immunoreactivity by 500 nmol DHPG was
      significantly blocked by intrastriatal infusion of the group I selective
      antagonist, n-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC,
      25 nmol), but not by the group II/III antagonist, (RS)-alpha-methylserine-o
      phosphate monophenyl ester (MSOPPE, 25 nmol). These data suggest that group I
      mGluR activation is positively linked to signaling cascades resulting in CREB,
      Elk-1, and ERK phosphorylation in the striatum in vivo.

PMID- 11597769
TI  - Impaired NMDA receptor function in mouse olfactory bulb neurons by tetracycline
      sensitive NR1 (N598R) expression.
AB  - High Ca(2+) permeability and its control by voltage-dependent Mg(2+) block are
      defining features of NMDA receptors. These features are lost if the principal NR1
      subunit carries an asparagine (N) to arginine (R) substitution in a critical
      channel site at NR1 position 598. NR1(R) expression from a single allele in gene
      targeted NR1(+/R) mice is lethal soon after birth, precluding analysis of altered
      synaptic functions later in life. We therefore employed the forebrain specific
      alphaCaMKII promoter to drive tTA-mediated tetracycline sensitive transcription
      of transgenes for NR1(R) and for lacZ as reporter. Transgene expression was
      observed in cortex, striatum, hippocampus, amygdala and olfactory bulb and was
      mosaic in all these forebrain regions. It was highest in olfactory bulb granule
      cells, in most of which Ca(2+) permeability and voltage-dependent Mg(2+) block of
      NMDA receptors were reduced to different extents. This indicates significant
      impairment of NMDA receptor function by NR1(R) in presence of the wild-type NR1
      complement. Indeed, even though NR1(R) mRNA constituted only 18% of the entire
      NR1 mRNA population in forebrain, the transgenic mice died during adolescence
      unless transgene expression was suppressed by doxycycline. Thus, glutamate
      receptor function can be altered in the mouse by regulated NR1(R) transgene
      expression.

PMID- 11597770
TI  - Lack of mu-opioid receptor leads to an increase in the NMDA receptor subunit mRNA
      expression and NMDA-induced convulsion.
AB  - The present study investigated in situ hybridization of N-methyl-D-aspartate
      (NMDA) receptor (NR) subunit mRNA and convulsion induced by
      intracerebroventricular injection of NMDA, in order to examine changes in NMDA
      receptor function in mu-opioid receptor gene knockout mice. Levels of NR1 and
      NR2A subunit mRNA were significantly increased in the parietal cortex (8.4 and
      10.6%, respectively) and hypothalamus (8.7 and 15.2%, respectively) in mu-opioid
      receptor knockout mice. Levels of NR2B subunit mRNA were noted to be increased in
      the parietal cortex (9.1%), thalamus (7.7%), and hypothalamus (10.4%) in mu
      opioid receptor knockout mice. The ED(50) for NMDA-induced convulsion in wild
      type mice was 0.20 microg/10 microl/mouse. The ED(50) in mu-opioid receptor
      knockout mice was 0.14 microg/10 microl/mouse. There is a significant difference
      in the potency ratio of wild-type mice versus knockout mice (potency ratio: 1.44,
      P < 0.05). These results indicate that mu-opioid receptor knockout mice are more
      sensitive to NMDA-induced convulsion. Therefore, these results suggest that
      absence of mu-opioid receptor gene is accompanied by changes in the NMDA receptor
      system which can modulate the synaptic excitability in the process such as
      convulsion or epilepsy.

PMID- 11597771
TI  - Hypothalamic CRH mRNA levels are differentially modulated by repeated 'binge'
      cocaine with or without D(1) dopamine receptor blockade.
AB  - We previously found that there was a rapid stimulatory effect of acute (1 day)
      'binge' cocaine on CRH mRNA levels in the rat hypothalamus. In contrast, after 3
      days of 'binge' cocaine, there was a modest decrease (12%) in hypothalamic CRH
      mRNA levels, which after 14 days of 'binge' cocaine was greater (32%) and
      significantly lower than control values. Also, our previous studies found an
      elevation of CRH mRNA in the frontal cortex after 3 days of 'binge' cocaine. The
      present study was designed to investigate the possible role of dopamine receptors
      in modulating these effects. Administration of 3 days of 'binge' cocaine (3 x 15
      mg/kg, i.p.) was preceded by daily injections of either D(1) (SCH23390, 2 mg/kg)
      or D(2) (sulpiride, 50 mg/kg) dopamine receptor antagonist. Neither SCH23390 nor
      sulpiride had an effect on basal CRH mRNA levels in the hypothalamus, frontal
      cortex or amygdala. Small decreases (10-13%) in hypothalamic CRH mRNA levels were
      found again to be induced by 3 days of repeated 'binge' cocaine. However, this
      modest decrease was not found in the rats that received D(1) antagonist SCH23390
      pretreatment. Pretreatment with D(2) antagonist sulpiride had no effect on this
      decrease. These findings suggest that the inhibitory effect of repeated 'binge'
      cocaine on the hypothalamic CRH mRNA expression is absent when there is D(1), but
      not D(2), dopamine receptor blockade. In the frontal cortex, pretreatment with
      either SCH23390 or sulpiride did not alter the increases in the CRH mRNA levels
      induced by repeated 'binge' cocaine. The results suggest that the cocaine-induced
      modulation of hypothalamic CRH mRNA expression is secondary to changes in the
      activity of specific components of dopaminergic systems.

PMID- 11597772
TI  - Structure and expression of the glycine cleavage system in rat central nervous
      system.
AB  - The glycine cleavage system (GCS) is a mitochondrial multienzyme system
      consisting of four individual proteins, three specific components (P-, T-, and H
      proteins) and one house-keeping enzyme, dihydrolipoamide dehydrogenase. Inherited
      deficiency of the GCS causes nonketotic hyperglycinemia (NKH), an inborn error of
      glycine metabolism. NKH is characterized by massive accumulation of glycine in
      serum and cerebrospinal fluids and severe neuronal dysfunction in neonates. To
      elucidate the neuropathogenesis of NKH, we cloned cDNAs encoding three specific
      components of the GCS and studied the gene expression in rat central nervous
      system. P-, T-, and H-protein cDNAs encoded 1024, 403, and 170 amino acids,
      respectively. In situ hybridization analysis revealed that P-protein mRNA was
      expressed mainly in glial-like cells, including Bergmann glias in the cerebellum,
      while T- and H-protein mRNAs were detected in both glial-like cells and neurons.
      T- and H-protein mRNAs, but not P-protein mRNA, were expressed in the spinal
      cord. Primary astrocyte cultures established from cerebral cortex had higher GCS
      activities than hepatocytes whereas those from spinal cord expressed only H
      protein mRNA and had no enzymatic activity. An important role of glycine as
      inhibitory neurotransmitter has been established in the brainstem and spinal cord
      and another role of glycine as an excitation modulator of N-methyl-D-aspartate
      receptor is suggested in the hippocampus, cerebral cortex, olfactory bulbus, and
      cerebellum. Our results suggest that the GCS plays a major role in the forebrain
      and cerebellum rather than in the spinal cord, and that N-methyl-D-aspartate
      receptor may participate in neuropathogenesis of NKH.

PMID- 11597773
TI  - Glutamine synthetase activity and expression are not affected by the development
      of motor neuronopathy in the G93A SOD-1/ALS mouse.
AB  - The expression and activity of the enzyme glutamine synthetase (GS) were examined
      in the G93A/SOD-1 transgenic mouse model of progressive motor neuronopathy to
      investigate the mechanisms underlying degeneration of the motor neurones.
      Clinical signs appeared in G93A/SOD-1 mice at around 90 days, with severe
      spasticity and loss of self-righting reflex from 120 to 150 days of age. GS
      expression was examined using western blotting in primary astrocyte cultures
      derived from newborn (P1-2) G93A/SOD-1 mice and their non-transgenic littermates
      and in lower spinal cord from animals at 30, 60 and 90 days of age and disease
      end-stage (120-150 days). There were no differences in the levels of GS
      expression in the transgenic mice compared to the unaffected littermates at any
      of the disease stages examined. GS activity was measured spectrophotometrically
      in spinal cord extracts at these disease stages. There was a decrease in V(max)
      at 60 days compared to 30 days in both groups of mice (3.48+/-0.58 cf. 6.43+/
      1.83 mmol/h/mg protein; non-transgenic littermates), with GS activity highest at
      end-stage (9.38+/-0.71 mmol/h/mg protein cf. 7.64+/-0.42 mmol/h/mg protein in
      littermates). Conversely, K(m) was transiently increased at 60 days (2.53+/-0.26
      mM cf. 1.32+/-0.20 in littermates), remaining within the range of 30 day
      measurements from 90 days onwards. There were no differences in V(max) or K(m)
      values between the G93A/SOD-1 mice and their unaffected non-transgenic
      littermates at any of the disease stages examined. We conclude that there is no
      evidence that a change in glutamine synthetase activity or expression contributes
      to the progressive neurodegeneration observed in the G93A/SOD-1 mice.

PMID- 11597774
TI  - Elements of angiotensin system are involved in leeches and mollusks immune
      response modulation.
AB  - We present immunocytochemical, biochemical and cellular evidences for the
      presence of a renin-angiotensin system (RAS) in coelomocytes of invertebrates
      (leech, Theromyzon tessulatum and mollusk Mytilus edulis). Leech coelomocytes are
      immunoreactive to polyclonal antisera raised against the T. tessulatum
      angiotensin-converting enzyme (ACE) and leech brain angiotensin II (AII) and a
      commercial anti-AT1 receptor. Biochemically, renin, ACE- and AT1-like receptor
      were identified in the leech immune cells. We further demonstrate that leech AII
      (10(-6) M) alone does not initiate nitric oxide (NO) release in invertebrate
      immunocytes but does only after pre-exposing the cells to IL-1 (15.9+/-2.6 nM;
      P<0.005 vs. 1.1 nM when AII is added alone). Similar results were obtained with
      human leukocytes (14.5+/-2.7 nM; P<0.005 IL-1+AII vs. 0.9 nM when AII is added
      alone). Then, an immunocytochemical study performed at the structural and
      ultrastructural levels confirmed the presence in same immune cells all the
      molecules of the renin-angiotensin system (RAS) in leeches as epitopes to IL-1
      like protein and IL-1-like receptor. This is the first report in invertebrates
      and of a co-action between cytokines like substances and neuropeptides in an
      immune process and the involvement of the RAS in modulation of the immune
      response.

PMID- 11597775
TI  - Acute ethanol administration differentially modulates mu opioid receptors in the
      rat meso-accumbens and mesocortical pathways.
AB  - Biochemical and pharmacological evidence suggest that the dopaminergic mesolimbic
      system plays a key role in mediating the reinforcing properties of alcohol and
      other drugs of abuse. Alcohol reinforcement and high alcohol drinking behavior
      have been postulated to be partially mediated by a neurobiological mechanism
      involving the alcohol-induced activation of the endogenous opioid system. The aim
      of this work was to study the effect of the in vivo acute administration of
      ethanol on mu (mu) opioid receptors in the rat dopaminergic meso-accumbens and
      mesocortical pathways by quantitative receptor autoradiography. [(3)H]DAMGO
      binding was significantly decreased in the ventral tegmental area (VTA) 30 min
      after ethanol administration. A small ethanol-induced reduction was observed in
      the shell region of the nucleus accumbens 1 h after exposure. In contrast, 2 h
      after ethanol administration, [(3)H]DAMGO binding was significantly increased in
      the frontal and prefrontal cortices. The observed changes correlated well with
      high ethanol plasma levels. Our results suggest that the reinforcing properties
      of ethanol may be partially mediated by mechanisms involving the ethanol-induced
      down- and up-regulation of mu receptors in the dopaminergic mesolimbic system. Mu
      receptors in the VTA and the frontal and prefrontal cortices may be involved in
      the in vivo acute responses to ethanol and could play a key role in modulating
      the dopaminergic activity of the mesocortical pathway in response to the drug. In
      contrast, the contribution of both mu and delta receptors in the nucleus
      accumbens might be relevant in these processes.

PMID- 11597776
TI  - Delayed induction of p38 MAPKs in reactive astrocytes in the brain of mice after
      KA-induced seizure.
AB  - Activation of p38 mitogen-activated protein kinase (p38 MAPK) has been implicated
      in pathological changes in inflammatory and apoptotic processes in various cell
      types including neurons. Here we report the delayed induction of p38 MAPKs in the
      brain of mice following kainic acid (KA)-induced seizure. The immunoreactivities
      of p38alpha and p38beta MAPKs were markedly increased in the brain 4 days after
      KA administration, especially in the areas undergoing selective neuronal loss. In
      particular, p38beta was dramatically increased in reactive astrocytes of CA3 and
      CA1 regions of hippocampus with its enriched localization in the nucleus of
      astrocytes. The induction of p38beta was sustained for more than 10 days after KA
      treatment. Pre-administration of the selective neuronal nitric oxide synthase
      (nNOS) inhibitor, 7-nitroindazole (7-NI), which suppressed the delayed neuronal
      death as well as astrogliosis in hippocampus of seizure-experienced animals,
      dramatically repressed the delayed induction of p38beta MAPK in astrocytes. The
      repression was reversed by the co-injection with L-arginine (L-arg), a substrate
      for NOS, which coincided with the aggravation of neuronal death. Together, these
      data suggested a role of p38 MAPK signal pathway in delayed neuronal death and/or
      in reactive gliosis in mice with KA-induced seizure.

PMID- 11597777
TI  - Up-regulation of D3 dopaminergic receptor mRNA in the core of the nucleus
      accumbens accompanies the development of seizures in a genetic model of absence
      epilepsy in the rat.
AB  - The basal ganglia system is thought to play a key role in the control of absence
      seizures and there is ample evidence that epileptic seizures modify brain
      dopamine function. We recently reported that local injections of dopamine D1 or
      D2 agonists in the core of the nucleus accumbens suppressed absence-seizures in a
      spontaneous, genetic rodent model of absence-epilepsy whereas injections of D1 or
      D2 antagonists had aggravating effects. These findings raised the possibility
      that the dopaminergic system may be altered in absence-epilepsy prone rats.
      Therefore, we studied by in situ hybridization histochemistry the expression of
      pre- and postsynaptic components of the dopaminergic system in this strain of
      rats. When compared to non-epileptic control rats, epileptic rats displayed no
      change in the expression of mRNAs coding for the neuronal dopaminergic markers
      (tyrosine hydroxylase, membraneous and vesicular dopamine transporters). In
      addition, there was no difference between the two strains concerning the
      expression of the dopamine receptor transcripts D1, D2 and D5. In adult absence
      epilepsy prone rat with an overt epileptic phenotype, however, an elevated level
      of D3 mRNA expression was observed in neurons of the core of the nucleus
      accumbens (+23% increase in silver grain density compared to non-epileptic
      control rats). D3 transcripts were not increased in juvenile epileptic rats
      without seizures. These findings suggests that up-regulation of D3 receptor mRNA
      is part of the epileptic phenotype in absence-epilepsy prone rats. Its
      localization in the core of the nucleus accumbens bears close resemblance to the
      dopamine-sensitive antiepileptic sites in ventral striatum and further support
      the involvement of ventral structures of the basal ganglia system in the control
      of absence-seizures.

PMID- 11597778
TI  - Differential effects of ischemia and reperfusion on c-Jun N-terminal kinase
      isoform protein and activity.
AB  - Activation of the c-Jun N-terminal (JNK) or stress-activated protein kinases
      (SAPK) is associated with a wide range of disparate cellular responses to
      extracellular stimuli, including either induction of or protection from
      apoptosis. This study investigates the effect of ischemia and reperfusion on JNK
      isoform activities using a reversible rabbit spinal cord ischemia model. High
      basal JNK activity, attributed to the p46 JNK1 isoform, was expressed in the CNS
      of untreated rabbits. JNK activity decreased in the lumbar spinal cord of rabbits
      occluded for 15-60 min. During reperfusion animals occluded for 15 min recovered
      neurological function and JNK activity returned to normal levels. In contrast
      animals occluded for 60 min remained permanently paraplegic and JNK activity was
      half the control activity after 18 h of reperfusion. In these animals proteolytic
      fragments of JNK1 and JNK3 were observed and protein levels, but not activity, of
      JNK isoforms increased in a detergent-insoluble fraction. Two novel c-Jun (and
      ATF-2) kinase activities increased during reperfusion of animals occluded for 60
      min. An activity designated p46(slow) was similar in M(r) to a JNK2 isoform
      induced in these animals. A second 30-kDa activity associated with the detergent
      insoluble fraction co-migrated with a JNK3 N-terminal fragment. The results show
      that JNK1 is active in the normal CNS and increased activity is not associated
      with durations of ischemia and reperfusion that induce cell death. However,
      specific JNK isoform activation may participate in the cell death pathways as
      increased activity of novel c-Jun (ATF-2) kinase activities was observed in
      paraplegic animals.

PMID- 11597779
TI  - Significance of the catechol-O-methyltransferase gene polymorphism in migraine.
AB  - The objective was to assess the significance of the catechol-o-methyltransferase
      (COMT) enzyme polymorphism in migraine. For this reason, 62 migraineurs and 64
      healthy volunteers were included in the study. The analysis of COMT polymorphism
      was performed using PCR. The H/H genotype was more frequent in the control group
      than in the patients group (P=0.032). The homozygous or heterozygous L allele was
      over represented in the migraineurs compared with the controls (P=0.013). The L/L
      genotype was over represented in the migraineurs who also had a family history of
      migraine (P=0.003). There was no relationship between aura and COMT genotypes. In
      conclusion, the COMT polymorphism may be of potential pharmacological importance
      regarding the individual differences in the metabolism of catechol drugs in
      migraineurs. Although altered catecholamine activity due to polymorphism of COMT
      gene may be one of the mechanisms involved in the pathogenesis of migraine, these
      mechanisms are not related to presence or absence of aura.

PMID- 11597780
TI  - Differential effects of morphine, DPDPE, and U-50488 on apomorphine-induced
      climbing behavior in mu-opioid receptor knockout mice.
AB  - The present study examined the hypothesis whether the opioid receptors (mu,
      delta, and kappa) contribute to a behavioral dopaminergic activation produced by
      dopamine receptor agonist, apomorphine, by comparing responses in wild type and
      mu-opioid receptor knockout mice. The data suggest that expression of mu-opioid
      receptors plays an important role in the enhancement of climbing behavior induced
      by apomorphine. Compared to wild type mice, a response in the dopaminergic
      behavior by treatment with delta-receptor agonist, DPDPE, is more sensitive to
      the mice lacking mu-opioid receptor. Treatment with kappa-receptor agonist, U
      50488, is potentiated the apomorphine-induced climbing behavior in wild type and
      mu-opioid receptor knockout mice. These responses may be independent of that
      through mu-opioid receptors. Therefore, the our results show that dopaminergic
      activation measured by climbing behavior in mu-opioid receptors knockout mice are
      differently regulated by mu-, delta-, and kappa-opioid receptor agonists.

PMID- 11597781
TI  - Expression of pituitary adenylate cyclase-activating polypeptide mRNA in the
      cochlea of rats.
AB  - Expression of mRNA for pituitary adenylate cyclase-activating polypeptide (PACAP)
      was detected in the cochlea of rats using a reverse transcription-polymerase
      chain reaction and in situ hybridization. Examination of in situ hybridization
      demonstrated that cells in the spiral ganglion, and marginal cells in the stria
      vascularis expressed mRNA for PACAP. These findings suggest that PACAP may play
      an important role in regulating cochlear functions.

PMID- 11597782
TI  - Nestin-like immunoreactivity of corpora amylacea in aged human brain.
AB  - Corpora amylacea (CA) are spherical bodies routinely observed throughout the aged
      human brain, normally found at high frequencies under the ependymal lining of the
      ventricles. We identified clusters of CA under the ependyma of the lateral and
      fourth ventricles in post-mortem brain material from Parkinson patients as well
      as age-matched controls. Using a monoclonal antibody we found CA to be
      immunoreactive for nestin, a marker of neural stem cells, while no other
      structures in the investigated brain areas were labeled by this antibody. Nestin
      filaments are therefore possible structural components of CA, a finding which may
      trigger new hypotheses regarding their biogenesis and function.

PMID- 11597783
TI  - Inhibitory effect of flavonoid derivatives on Epstein-Barr virus activation and
      two-stage carcinogenesis of skin tumors.
AB  - To search for possible anti-tumor promoters, ten flavonoid derivatives (1-10)
      synthesized from morin and quercetin were examined for their inhibitory effects
      on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in
      vitro assay. Of these compounds, pentaallyl ethers (9, 10) showed significant
      inhibitory effects on EBV-EA activation induced by the tumor promoter, 12-O
      tetradecanoylphorbol 13-acetate. Further, quercetin pentaallyl ether (10)
      exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in
      vivo two-stage carcinogenesis test.

PMID- 11597784
TI  - Hydrocarbon carcinogens induce p53 activity in normal mouse tissue.
AB  - Previous studies led to the suggestion that a sub class of hydrocarbon
      carcinogens have the capacity of damage DNA and evade normal cellular defence
      mechanisms. To examine the ability of hydrocarbon carcinogens to induce p53
      transcriptional activity in normal tissues, we have used transgenic mice in which
      LacZ transgene is driven by a p53 response element. We demonstrate that
      transcriptionally active p53 is induced in normal tissue after exposure to
      putative stealth carcinogens in an identical manner to non-stealth agents.

PMID- 11597785
TI  - Attenuation of catalase activity in the malignant phenotype plays a functional
      role in an in vitro model for tumor progression.
AB  - We have developed an in vitro model to study the molecular mechanisms of tumor
      progression. Using repeated treatments with ionizing radiation or N-methyl-N'
      nitro-N-nitrosoguanidine (MNNG), we caused malignant progression of a papilloma
      producing mouse keratinocyte cell line, 308 cells. In a previous study we have
      shown that the malignant variants of 308 cells have elevated reactive oxygen
      species (ROS) levels, and have established a functional role for the pro-oxidant
      state in the progressed phenotype (Carcinogenesis 20 (1999) 2063). In this study,
      we have evaluated the status of intracellular defense mechanisms for ROS
      scavenging in the progressed phenotype to identify sources that contribute to
      their pro-oxidant state. Our results demonstrate that a reduction in several anti
      oxidant defense mechanisms, including catalase and glutathione S-transferase mu,
      correlates with the emergence of the malignant phenotype. We provide evidence
      that attenuation of catalase activity may play a functional role in the malignant
      progression of mouse keratinocytes.

PMID- 11597786
TI  - Diet and the duration of testosterone-dependent prostate cancer in Lobund-Wistar
      rats.
AB  - Hormone-related cancers in the prostate, breast, endometrium, ovary and testicle
      account for 30% of malignancies in humans. We have developed a unique model of
      spontaneous prostate cancer (PC) in Lobund-Wistar [L-W] rats that shares many of
      its characteristics with the natural history of PC in man, including (a) inherent
      predisposition, high production of testosterone and aging risk factors, (b)
      endogenous tumorigenic mechanisms, and (c) early stage testosterone-dependent and
      late stage testosterone-independent tumors. About 30% of L-W rats on diet L-485
      develop spontaneous palpable cancer in the anterior prostate-seminal vesicle (P
      SV) complex in average of 20.5 months. At age 12 months early stage spontaneous
      PC was prevented or reversed by testosterone-deprivation through change of diet
      from L-485 to soy protein isolate/isoflavone (SPII) diet, thereby preventing the
      late lethal clinical disease: about 75% of rats at risk of developing
      testosterone-independent P-SV tumors were free of detectable cancer and about 25%
      had developed testosterone-independent cancer at age 12 months. The duration of
      the dependent stage exceeded age 12 months in 75% of the rats at risk. Dietary
      soymeal, found in most natural ingredient diets, may promote PC tumorigenesis,
      but only in L-W rats.

PMID- 11597787
TI  - Cancer chemopreventive activity of phenylpropanoid esters of sucrose, vanicoside
      B and lapathoside A, from Polygonum lapathifolium.
AB  - To search for cancer chemopreventive agents from natural resources, many
      phytochemicals have been screened using the in vitro synergistic assay indicated
      by the inhibitory effects on the induction of Epstein-Barr virus early antigen
      (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA). Two phenylpropanoid
      esters of sucrose, vanicoside B and lapathoside A, were isolated from the aerial
      part of Polygonum lapathifolium as inhibitors on the EBV-EA induction. These
      compounds also exhibited significant anti-tumor-promoting effects on mouse two
      stage skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA, as an
      initiator) and TPA as a promoter. Further, vanicoside B exhibited the remarkable
      inhibitory effect on two-stage carcinogenesis test of mouse skin tumors initiated
      with an NO donor, NOR-1.

PMID- 11597788
TI  - Fatty acid composition of lymphocyte membrane phospholipids in children with
      acute leukemia.
AB  - The composition of phospholipid fatty acids (PLFA) of separated mononuclear blood
      cells (MNC) from patients with leukemia was established by high-resolution gas
      chromatography. Abnormal fatty acid concentrations are detected in the MNC
      membrane phospholipids in patients with acute lymphoblastic leukemia (ALL)
      without a deficiency of essential fatty acids (EFA). Significantly reduced
      relative levels of linoleic acid (4.35 vs. 7.82%; P<0.001) are found in the MNC
      PL in patients with ALL as compared to a healthy control group. Moreover, the
      Delta6-desaturated fatty acids are increased: gamma-linoleic acid (3.56 vs.
      0.17%; P<0.001), arachidonic acid (21.82 vs. 16.27%; P<0.05), docosatetraenoic
      acid (3.52 vs. 1.56%; P<0.001), docosapentaenoic acid (0.34 vs. 0.04%; P<0.001),
      octadecatetraenoic acid (0.53 vs. 0.23%; P<0.05), eicosatetraenoic acid (1.83 vs.
      0.08%; P<0.001) and docosahexaenoic acid (2.77 vs. 1.54%; P<0.001). A increased
      Delta(6)-desaturase activity is postulated as the cause for the increased level
      of desaturate products or the increased Delta6-activity index (Ratio of gamma
      linoleic acid+dihomogamma-linolenic acid to linoleic acid) (1.21 vs. 0.27;
      P<0.001). The Delta6-enzyme activities measured using linoleic acid and alpha
      linoleic acid as substrate underscore these findings (Delta6(n-6); 2.49 vs. 0.65
      and Delta6(n-3); 2.75 vs. 1.12 nmol x h(-1)/10(8) MNC). In contrast, patients
      with acute myeloid leukemia (AML) do not show any significant differences in the
      lymphocyte membrane PLFA and no Delta6-desaturase abnormalities.

PMID- 11597789
TI  - Intratumoral delivery of an interferon gamma retrovirus-producing cells inhibits
      growth of a murine melanoma by a non-immune mechanism.
AB  - Interferon gamma (IFNgamma) is a potent inhibitor of cell growth effective
      against a wide range of tumor-derived cell lines. We cloned murine IFNgamma cDNA
      into a retroviral vector and created a packaging cell line (Am-gamma) producing
      this IFNgamma-encoding retrovirus. In a pilot experiment, admixing and co
      injection of equal numbers of retrovirus-producing and target B16 melanoma cells
      led to high rates of infection and strong suppression of neoplastic growth. This
      effect was observed in the absence of measurable systemic production of IFNgamma
      and could be reproduced in animals lacking cytotoxic immune responses. Tumor
      angiogenesis was unaffected and no increase in apoptosis was apparent; however,
      mitotic indices were greatly reduced in Am-gamma-containing abortive tumors. We
      thus concluded that IFNgamma directly affects proliferation of B16 cells. Indeed,
      exposure of B16 cells to IFNgamma in vitro inhibits cell division, as measured by
      a thymidine incorporation assay. Most importantly, repeated intratumoral
      injections of Am-gamma stunted growth of established B16 melanomas in 75% of
      treated animals. Thus, this approach can serve as a prototype for new anti-cancer
      modalities.

PMID- 11597790
TI  - Lung cancer susceptibility in relation to combined polymorphisms of microsomal
      epoxide hydrolase and glutathione S-transferase P1.
AB  - Human microsomal epoxide hydrolase (mEH) catalyzes a key step in the
      biotransformation of benzo[a]pyrene that yields the highly mutagenic (+)-anti-7,8
      diol-9,10 epoxide (BPDE). Two polymorphisms have been described in the coding
      region of the mEH gene (EPHX1) that produce two protein variants: 113Tyr-->113His
      (exon 3) and 139His-->139Arg (exon 4). We performed a case-control study among
      Northwestern Mediterranean Caucasians to investigate a possible association
      between these EPHX1 variants and lung cancer risk. Both EPHX1 polymorphisms were
      analyzed in a group of lung cancer patients (n=176) and in a control group of
      healthy smokers (n=187). The results showed a significantly decreased risk for
      the rare homozygous 113His/113His (adjusted odds ratio (OR): 0.44, 95% confidence
      interval (CI): 0.27-0.71) and 139Arg/139Arg (adjusted OR: 0.55, 95% CI: 0.33
      0.91) compared with the major wild-types 113Tyr/113Tyr and 139His/139His,
      respectively, as the references. Thereafter, we analyzed the EPHX1 variants in
      combination with three glutathione S-transferase polymorphic genes (GSTM1, GSTT1,
      and GSTP1) and we found a significant overepresentation of cancer patients with a
      combination of exon 3 113Tyr/113Tyr EPHX1 and exon 5 105Ile/105Ile GSTP1
      (adjusted OR: 2.34, 95% CI: 1.21-4.52). The polymorphic site within the exon 5 of
      GSTP1 results in a Ile-->Val substitution, and the isoleucine GSTpi isoform has
      been found in vitro to be less active than the valine isoform towards the
      conjugation of BPDE. The 113 Tyr/Tyr EPHX1 encodes for a high-activity mEH. Our
      results agree with these observations in vitro and suggest that a genetically
      determined combination of a high-activity mEH and a low-activity GSTpi may
      increase lung cancer risk among smokers.

PMID- 11597792
TI  - Matrilysin stimulates DNA synthesis of cultured vascular endothelial cells and
      induces angiogenesis in vivo.
AB  - Matrilysin produced by human colon cancer cells may be involved in the
      progression and metastasis of cancer. In the present study, we investigated the
      association of matrilysin with angiogenesis. One microgram of recombinant
      matrilysin is confirmed to have increased [3H]-thymidine uptake in human
      umbilical vein endothelial cells. Then we used micro encapsulation and a mouse
      hemoglobin enzyme-linked immunosorbent assay system for in vivo quantitation of
      angiogenesis with BALB/c nu/nu athymic mice. Hundred micrograms of recombinant
      matrilysin induced angiogenesis to the same degree as 10 microg of basic
      fibroblast growth factor (bFGF). Angiogenesis was observed at the site implanted
      with human colon cancer WiDr cells in agarose micro beads. This was inhibited by
      subcutaneous injection of matrilysin-specific antisense oligonucleotide
      significantly by 53%. In conclusion, matrilysin may be associated with
      angiogenesis of human colon cancer through the direct proliferative action on
      endothelial cells.

PMID- 11597791
TI  - Inhibition of apoptosis by pentachlorophenol in v-myc-transfected rat liver
      epithelial cells: relation to down-regulation of gap junctional intercellular
      communication.
AB  - Pentachlorophenol (PCP), a promoter of murine hepatocarcinogenesis, inhibits gap
      junctional intercellular communication (GJIC) in rat liver epithelial cells in
      vitro. To test the hypothesis that both inhibition of GJIC and apoptosis
      contribute to tumor promotion, we investigated the effect of PCP on both GJIC and
      serum deprivation-induced apoptosis in v-myc-transfected rat liver epithelial
      cells. The results showed that PCP inhibited apoptosis, as measured by the TUNEL
      assay and DNA ladder formation. Inhibition of apoptosis was associated with a
      decrease in GJIC. The study demonstrated that PCP has a potential for inhibiting
      apoptosis and GJIC, supporting the hypothesis.

PMID- 11597793
TI  - Increased serum VEGF in 13 children with Wilms' tumour falls after surgery but
      rising levels predict poor prognosis.
AB  - Vascular endothelial cell growth factor (VEGF, a potent endothelial cell mitogen
      in vitro) may be important in tumour development and its spread in vivo. In this
      preliminary study, we tested the hypotheses that (i) raised serum levels in
      Wilms' tumour fall after surgery, and (ii) rising levels predict adverse outcome.
      Serum VEGF was measured (ELISA) in 13 children about to undergo surgery, and
      serially on the following day, a week later, and finally 3-6 months after
      surgery. A simple follow-up at 6 months was also performed. The control group was
      60 healthy adults. Before surgery, the median (inter-quartile range) VEGF in the
      children was 20 ng/ml (10.4-70.5) and was 1 ng/ml (0.5-4.0) in the adults. This
      difference is statistically highly significant (P=0.0001). After surgery, levels
      in the children fell significantly to 1.3 ng/ml (0.5-7.95) the following day and
      to 1.9 ng/ml (0.5-5.0) the following week (P<0.001, ANOVA). Six months after
      surgery, three of the children had died. A level of >10 ng/ml measured 3 months
      after surgery correctly identified all three deaths: levels were 1.3 ng/ml (0.5
      1.9) in the survivors and were 20.0 ng/ml (15-104) in those who died. These data
      indicate a rapid reduction in raised VEGF following surgery for Wilms' tumour,
      but that rising levels predict poor prognosis.

PMID- 11597794
TI  - Expression of the cdc25B gene as a prognosis marker in non-small cell lung
      cancer.
AB  - There is an evidence to suggest that cdc25B phosphatase is an oncogenic. We
      hypothesized that cdc25B gene may be expressed in tumors of patients with non
      small cell lung cancer (NSCLC) and affect their clinical outcome. Expression of
      cdc25B messenger RNA was evaluated by reverse transcription polymerase chain
      reaction in 55 non-small cell lung carcinomas and adjacent histological normal
      lung samples using LightCycler. The data was analyzed in reference to
      clinicopathological data and survival data. There was no difference of cdc25B
      expression level between the NSCLC tissue and normal lung tissue. There was no
      relationship between cdc25B gene expression and age, gender, N or T-status and
      clinical stage. However, the NSCLC patients with high cdc25B expression had
      significantly poor survival than the patients with low cdc25B expression
      (P=0.0173). Thus we suggest that cdc25B may predict poor survival.

PMID- 11597795
TI  - Randomized trial addressing risk features and time factors of surgery plus
      radiotherapy in advanced head-and-neck cancer.
AB  - PURPOSE: A multi-institutional, prospective, randomized trial was undertaken in
      patients with advanced head-and-neck squamous cell carcinoma to address (1) the
      validity of using pathologic risk features, established from a previous study, to
      determine the need for, and dose of, postoperative radiotherapy (PORT); (2) the
      impact of accelerating PORT using a concomitant boost schedule; and (3) the
      importance of the overall combined treatment duration on the treatment outcome.
      METHODS AND MATERIALS: Of 288 consecutive patients with advanced disease
      registered preoperatively, 213 fulfilled the trial criteria and went on to
      receive therapy predicated on a set of pathologic risk features: no PORT for the
      low-risk group (n = 31); 57.6 Gy during 6.5 weeks for the intermediate-risk group
      (n = 31); and, by random assignment, 63 Gy during 5 weeks (n = 76) or 7 weeks (n
      = 75) for the high-risk group. Patients were irradiated with standard techniques
      appropriate to the site of disease and likely areas of spread. The study end
      points were locoregional control (LRC), survival, and morbidity. RESULTS:
      Patients with low or intermediate risks had significantly higher LRC and survival
      rates than those with high-risk features (p = 0.003 and p = 0.0001,
      respectively), despite receiving no PORT or lower dose PORT, respectively. For
      high-risk patients, a trend toward higher LRC and survival rates was noted when
      PORT was delivered in 5 rather than 7 weeks. A prolonged interval between surgery
      and PORT in the 7-week schedule was associated with significantly lower LRC (p =
      0.03) and survival (p = 0.01) rates. Consequently, the cumulative duration of
      combined therapy had a significant impact on the LRC (p = 0.005) and survival (p
      = 0.03) rates. A 2-week reduction in the PORT duration by using the concomitant
      boost technique did not increase the late treatment toxicity. CONCLUSIONS: This
      Phase III trial established the power of risk assessment using pathologic
      features in determining the need for, and dose of, PORT in patients with advanced
      head-and-neck squamous cell cancer in a prospective, multi-institutional setting.
      It also revealed the impact of the overall treatment time in the combination of
      surgery and PORT on the outcome in high-risk patients and showed that PORT
      acceleration without a reduction in dose by a concomitant boost regimen did not
      increase the late complication rate. These findings emphasize the importance of
      coordinated interdisciplinary care in the delivery of combined surgery and RT.

PMID- 11597796
TI  - Potential role of intensity-modulated radiotherapy in the treatment of tumors of
      the maxillary sinus.
AB  - PURPOSE: To assess 3-dimensional conformal radiotherapy (3D-CRT) and intensity
      modulated radiotherapy (IMRT) techniques to see whether doses to critical
      structures could be reduced while maintaining planning target volume (PTV)
      coverage in patients receiving conventional radiotherapy (RT) for carcinoma of
      the maxillary sinus because of the risk of radiation-induced complications,
      particularly visual loss. METHODS AND MATERIALS: Six patients who had recently
      received conventional RT for carcinoma of the maxillary sinus were studied.
      Conventional RT, 3D-CRT, and step-and-shoot IMRT plans were prepared using the
      same 2-field arrangement. The effect of reducing the number of segments in the
      IMRT beams was investigated. RESULTS: 3D-CRT and IMRT reduced the brain and
      ipsilateral parotid gland doses compared with the conventional plans. IMRT
      reduced doses to both optic nerves; for the contralateral optic nerve, 15-segment
      IMRT plans delivered an average maximal dose of 56.4 Gy (range 53.9-59.3)
      compared with 65.7 Gy (range 65.3-65.9) and 64.2 Gy (range 61.4-65.6) for
      conventional RT and 3D-CRT, respectively. IMRT also gave improved PTV homogeneity
      and improved coverage, with an average of 8.5% (range 7.0-11.7%) of the volume
      receiving <95% of the prescription dose (64 Gy) compared with 14.7% (range 14.1
      15.9%) and 15.1% (range 14.4-16.1%) with conventional RT and 3D-CRT,
      respectively. Little difference was found between the 15 and 7-segment plans, but
      5 segments resulted in a reduced minimal PTV dose. CONCLUSIONS: IMRT offers
      significant advantages over conventional RT and 3D-CRT techniques for treatment
      of maxillary sinus tumors. Good results can be obtained from 7 segments per beam
      without compromising the PTV coverage. This number of segments is practical for
      implementation in a busy RT department.

PMID- 11597797
TI  - Important prognostic factors in patients with skull base erosion from
      nasopharyngeal carcinoma after radiotherapy.
AB  - PURPOSE: To evaluate the long-term outcome and prognostic factors in patients
      with skull base erosion from nasopharyngeal carcinoma after initial radiotherapy
      (RT). METHODS AND MATERIALS: From January 1985 to December 1986, 100 patients (71
      males, 29 females) with a diagnosis of nasopharyngeal carcinoma were found on
      computed tomography (CT) to have skull base erosion. The mean age was 41 years
      (range 16-66). Ninety-six patients had World Health Organization type III
      undifferentiated carcinoma, and 4 had type I. The metastatic workup, including
      chest radiography, liver ultrasound scanning, and liver function test was
      negative. All patients underwent external beam RT (EBRT) alone to 66-80 Gy during
      6-8 weeks. A daily fraction size of 2 Gy was delivered using 60Co or a linear
      accelerator. No patient received chemotherapy. All patients were followed at
      regular intervals after irradiation. The median follow-up was 22.3 months (range
      2-174). Survival of the cohort was computed by the Kaplan-Meier method. The
      potential prognostic factors of survival were examined. Multivariate analyses
      were performed using the Cox regression model. RESULTS: The 1, 2, 5, and 10-year
      overall survival rate for the cohort was 79%, 41%, 27%, and 13%, respectively.
      However, the subgroup of patients with both anterior cranial nerve (I-VIII) and
      posterior cranial nerve (IX-XII) involvement had a 5-year survival of only 7.7%.
      A difference in the time course of local recurrence and distant metastasis was
      observed. Both local recurrence and distant metastasis often occurred within the
      first 2 years after RT. However, local relapse continued to occur after 5 years.
      In contrast, no additional distant metastases were found after 5 years. The
      causes of death included local recurrence (n = 59), distant metastasis (n = 21),
      both local recurrence and distant metastasis (n = 1), and unrelated causes (n =
      5). After multivariate analysis, complete recovery of cranial nerve involvement,
      cranial nerve palsy, and headache after irradiation were found to be independent
      prognostic factors in this cohort. CONCLUSIONS: We present one of the longest
      follow-ups of patients with nasopharyngeal carcinoma invading the skull base. Our
      results demonstrate the importance of cranial nerve involvement, recovery of
      headache, and cranial nerve palsy. These factors should be carefully evaluated
      from the history, physical examination, and imaging studies. A subgroup of
      patients with skull base involvement had long-term survival after RT alone. The
      findings of this study are important as a yardstick against which more aggressive
      strategies, such as combined radiochemotherapy and altered fractionation RT can
      be compared.

PMID- 11597798
TI  - Hypothyroidism incidence after multimodality treatment for stage III and IV
      squamous cell carcinomas of the head and neck.
AB  - PURPOSE: Treatment of head-and-neck cancer patients with surgery, radiotherapy
      (RT), and chemotherapy has been associated with posttherapy hypothyroidism (HT).
      We evaluated the rate of posttherapy HT in patients with locally advanced
      squamous cell carcinoma of the head and neck, treated with multimodality therapy
      to determine which factors might predict this condition and at what interval the
      condition developed. METHODS: We reviewed the prospectively collected thyroid
      function data of patients treated with sequential chemotherapy, RT, and neck
      dissection. The incidence of posttherapy HT was estimated. The patient, tumor,
      and treatment factors possibly associated with HT were evaluated. RESULTS: Of 203
      patients, 118 had data adequate for evaluation. HT developed in 45% at a median
      of 24.4 months after therapy. HT occurred in 14% and 27% of patients at 6 months
      and 1 year after treatment, respectively. Univariate and multivariate analyses of
      sex, age, RT dose, RT fractionation, T and N stage, tumor site, and neck
      dissection failed to identify a clinically relevant risk factor. CONCLUSIONS: A
      high number of patients undergoing aggressive organ-sparing multimodality therapy
      for advanced squamous cell carcinoma of the head and neck are at risk for
      subsequent HT. We recommend that all patients definitively irradiated to the head
      and neck region undergo frequent serum thyroid-stimulating hormone screening for
      HT, beginning 6 months after RT.

PMID- 11597800
TI  - A prospective quality-of-life study in men with clinically localized prostate
      carcinoma treated with radical prostatectomy, external beam radiotherapy, or
      interstitial brachytherapy.
AB  - PURPOSE: To prospectively assess the health-related quality of life (HRQOL) and
      changes in HRQOL during the first year after 3 different treatments for
      clinically localized prostate cancer. METHODS AND MATERIALS: Ninety men with T1
      T2 adenocarcinoma of the prostate were treated with curative intent between May
      1998 and June 1999 and completed a quality-of-life Functional Assessment of
      Cancer Therapy-Prostate (FACT-P) questionnaire before treatment (T0) and 1 month
      (T1), 3 months (T3), and 12 months (T12) after treatment. Forty-four men were
      treated with permanent source interstitial brachytherapy (IB), 23 received
      external beam radiotherapy (EBRT), and 23 men were treated with radical
      prostatectomy (RP). The mean age of the entire study population was 65.9 years
      (median 67, range 42-79). The mean pretreatment prostate-specific antigen level
      of the entire study population was 6.81 ng/mL (median 6.25, range 1.33-19.6). The
      Gleason score was <or=6 in 65 (72%) of 90. The repeated measures analysis of
      variance and analysis of covariance were conducted on all quality-of-life and
      urinary outcome measures. RESULTS: A comparison of the demographic
      characteristics of the 3 treatment groups demonstrated significant differences.
      The men treated with RP were significantly younger than the men in either the IB
      or EBRT group (median age 61.0 RP, 67.1 IB, 68.8 EBRT; p = 0.0006). The men in
      the IB group were more likely to have a Gleason score of <or=6 than the EBRT
      group (Gleason score <or=6, 86% IB and 48% EBRT; p = 0.015). The mean score
      (standard deviation) at T0, T1, T3, and T12 for the FACT-P questionnaire for each
      group was as follows: IB 138.4 (17.0), 120.5 (21.7), 130.0 (18.4), and 138.5
      (14.2); EBRT 137.1 (12.1), 129.5 (21.0), 134.4 (19.2), and 136.9 (15.6); and RP
      138.3 (14.7), 117.7 (18.3), 134.4 (17.8), and 140.4 (14.9), respectively.
      Statistically significant differences over time were observed for the FACT-P in
      the IB and RP groups (p <0.0001), but not for the EBRT group (p = 0.08). The
      examination of the subscales within the FACT-P instrument demonstrated
      statistically significant changes over time in the IB and RP groups for the
      following: physical well-being, functional well-being, and prostate cancer
      symptoms. After adjusting for age, race, T stage, Gleason score, use of hormonal
      therapy, and baseline FACT-P scores, statistically significant differences in the
      FACT-P score at T1 according to treatment group were observed. At T12, the FACT-P
      scores were not significantly different than the baseline FACT-P scores for any
      group. CONCLUSIONS: The results of this analysis suggest that significant
      decreases in HRQOL, as measured by the FACT-P instrument, are evident in the
      first month after IB or RP, but not after EBRT. One year after treatment,
      however, the FACT-P scores were not statistically different from the baseline
      measures for any group. For all treatment groups, most of the HRQOL decreases
      were observed in the physical, functional, and prostate cancer-specific domains.
      These results suggest that the HRQOL changes are likely to be treatment-specific,
      further emphasizing the importance of a randomized trial comparing the different
      treatment options in this population of men.

PMID- 11597799
TI  - Phase I/II trial evaluating combined radiotherapy and in situ gene therapy with
      or without hormonal therapy in the treatment of prostate cancer--a preliminary
      report.
AB  - PURPOSE: To report the preliminary results of a Phase I/II study combining
      radiotherapy and in situ gene therapy (adenovirus/herpes simplex virus thymidine
      kinase gene/valacyclovir) with or without hormonal therapy in the treatment of
      prostate cancer. METHODS AND MATERIALS: Arm A: low-risk patients (T1-T2a, Gleason
      score <7, pretreatment PSA <10) were treated with combined radio-gene therapy. A
      mean dose of 76 Gy was delivered to the prostate with intensity-modulated
      radiotherapy. Arm B: high-risk patients (T2b-T3, Gleason score >or=7,
      pretreatment PSA >or=10) were treated with combined radio-gene therapy and
      hormonal therapy. Hormonal therapy was comprised of a 4-month leuprolide
      injection and 2-week use of flutamide. Arm C: Stage D1 (positive pelvic lymph
      node) patients received the same regimen as Arm B, with the additional 45 Gy to
      the pelvic lymphatics. Treatment-related toxicity was assessed using Cancer
      Therapy Evaluation Program common toxicity score and Radiation Therapy Oncology
      Group (RTOG) toxicity score. RESULTS: Thirty patients (13 in Arm A, 14 in Arm B,
      and 3 in Arm C) completed the trial. Median follow-up was 5.5 months. Eleven
      patients (37%) developed flu-like symptoms (Cancer Therapy Evaluation Program
      Grade 1) of fatigue and chills/rigors after gene therapy injection but recovered
      within 24 h. Four patients (13%) and 2 patients (7%) developed Grade 1 and 2
      fever, respectively. There was no patient with weight loss. One patient in Arm B
      developed Grade 3 elevation in liver enzyme, whereas 11 and 2 patients developed
      Grade 1 and 2 abnormal liver function tests. There was no Grade 2 or above
      hematologic toxicity. Three patients had transient rise in creatinine. There was
      no RTOG Grade 3 or above lower gastrointestinal toxicity. Toxicity levels were as
      follows: 4 patients (13%), Grade 2; 6 patients (20%), Grade 1; and 20 patients
      (67%), no toxicity. There was 1 patient with RTOG Grade 3 genitourinary toxicity,
      12 patients (40%) with Grade 2, 8 patients (27%) with Grade 1, and 9 patients
      (30%) with no toxicity. No patient dropped out from the trial or had to withhold
      treatment because of severe toxicity. CONCLUSIONS: This is the first trial of its
      kind in the field of prostate cancer that aims to expand the therapeutic index of
      radiotherapy by combining in situ gene therapy. Initial experience has
      demonstrated the safety of this approach. There is no added toxicity to each
      therapy used alone. Long-term follow-up and larger cohort studies are warranted
      to evaluate long-term toxicity and efficacy.

PMID- 11597801
TI  - Salvage external beam radiotherapy for clinical failure after cryosurgery for
      prostate cancer.
AB  - PURPOSE: To investigate the role of external beam radiotherapy (EBRT) as salvage
      treatment of prostate cancer after cryosurgery failure. METHODS AND MATERIALS:
      Between 1993 and 1998, 6 patients underwent EBRT with curative intent for local
      recurrence of prostate cancer after cryosurgery. All 6 patients had biopsy-proven
      recurrence and palpable disease on digital rectal examination at the time of
      EBRT. The median follow-up was 34 months (range 8-46). The median prostate
      specific antigen level was 2.3 ng/mL (range 0.8-4.1). No patient had evidence of
      metastatic disease. Two patients received hormonal therapy before beginning EBRT.
      No patient received hormonal therapy after EBRT completion. The median elapsed
      time between cryosurgery and EBRT was 3 years (range 1.5-4). The median delivered
      dose was 66 Gy (range 62-70.2) using a 10-MeV photon beam. An in-house-developed
      three-dimensional treatment planning system was used to plan delivery of the
      prescribed dose with conformal radiotherapy techniques. RESULTS: After EBRT, all
      patients had complete resolution of palpable disease. Four patients (66%) were
      disease free at the time of the last follow-up. Two patients developed
      biochemical failure as defined by the American Society for Therapeutic Radiology
      and Oncology consensus definition. One of these patients had a prostate-specific
      antigen level of 97 ng/mL before cryosurgery. No patient developed distant
      metastasis during follow-up. Two patients (33%) developed proctitis; 1 case
      resolved with Rowasa suppositories and 1 required blood transfusion. CONCLUSIONS:
      Our preliminary results suggest that EBRT can render a significant number of
      patients biochemically free of disease and can cause complete resolution of
      clinically palpable disease after initial cryosurgery. The results also showed
      that EBRT can be given without excessive morbidity. EBRT should be considered as
      a treatment option in these potentially curable cases.

PMID- 11597802
TI  - The effect of oral sucralfate on the acute proctitis associated with prostate
      radiotherapy: a double-blind, randomized trial.
AB  - PURPOSE: Acute rectal complications occur in the majority of patients receiving
      external-beam radiotherapy for carcinoma of the prostate. Sucralfate has been
      proposed to reduce radiation-induced mucosal injury by forming a protective
      barrier on ulcer bases, binding local growth factors, and stimulating
      angiogenesis. However, there is conflicting clinical evidence as to whether
      sucralfate, taken prophylactically during radiotherapy, can ameliorate the
      symptoms of acute radiation proctitis. METHODS AND MATERIALS: A double-blind
      randomized trial was conducted at four Radiation Oncology Departments in Sydney,
      Australia, between February 1995 and June 1997. A total of 338 patients with
      clinically localized prostate cancer receiving small volume radiotherapy, of whom
      335 were evaluable, were randomized to receive either 3 g of oral sucralfate
      suspension or placebo twice a day during radiotherapy. Patients kept a daily
      record of their bowel symptoms and were graded according to the RTOG/EORTC acute
      toxicity criteria. RESULTS: One hundred sixty-four patients received sucralfate
      and 171 received placebo. Both groups were well balanced with regard to patient,
      tumor, treatment factors, and baseline symptoms, except that the placebo group
      had a significantly more liquid baseline stool consistency score (p = 0.004).
      Patients kept a daily diary of symptoms during radiotherapy. After adjusting for
      baseline values, there was no significant difference between the two groups with
      regard to stool frequency (p = 0.41), consistency (p = 0.20), flatus (p = 0.25),
      mucus (p = 0.54), and pain (p = 0.73). However, there was more bleeding in the
      sucralfate group, with 64% of patients noticing rectal bleeding, compared with
      47% in the placebo group (p = 0.001). There was no significant difference between
      the two groups with respect to RTOG/EORTC acute toxicity (p = 0.88; sucralfate
      13%, 44%, 43% and placebo 15%, 44%, 40% for grade 0, 1, and 2, respectively).
      CONCLUSION: This study suggests that oral sucralfate taken prophylactically
      during radiotherapy does not ameliorate the symptoms of acute radiation proctitis
      and may increase acute bleeding. The cause of the increased bleeding in the
      sucralfate group is unclear. As the pathogenesis of acute and late reactions are
      different, late follow-up, which includes sigmoidoscopic evaluation, is currently
      being performed on this cohort of patients.

PMID- 11597803
TI  - Argon plasma coagulation for rectal bleeding after prostate brachytherapy.
AB  - PURPOSE: To better define the efficacy and safety of argon plasma coagulation
      (APC), specifically for brachytherapy-related proctitis, we reviewed the clinical
      course of 7 patients treated for persistent rectal bleeding. Approximately 2-10%
      of prostate cancer patients treated with 125I or 103Pd brachytherapy will develop
      radiation proctitis. The optimum treatment for patients with persistent bleeding
      is unclear from the paucity of available data. Prior reports lack specific
      dosimetric information, and patients with widely divergent forms of radiation
      were grouped together in the analyses. METHODS AND MATERIALS: Seven patients were
      treated with APC at the Veterans Affairs Puget Sound Health Care System and the
      University of Washington from 1997 to 1999 for persistent rectal bleeding due to
      prostate brachytherapy-related proctitis. Four patients received supplemental
      external beam radiation, delivered by a four-field technique. A single
      gastroenterologist at the Veterans Affairs Puget Sound Health Care System treated
      6 of the 7 patients. If the degree of proctitis was limited, all sites of active
      bleeding were coagulated in symptomatic patients. An argon plasma coagulator
      electrosurgical system was used to administer treatments every 4-8 weeks as
      needed. The argon gas flow was set at 1.6 L/min, with an electrical power setting
      of 40-45 W. RESULTS: The rectal V100 (the total rectal volume, including the
      lumen, receiving the prescription dose or greater) for the 7 patients ranged from
      0.13 to 4.61 cc. Rectal bleeding was first noticed 3-18 months after
      implantation. APC (range 1-3 sessions) was performed 9-22 months after
      implantation. Five patients had complete resolution of their bleeding, usually
      within days of completing APC. Two patients had only partial relief from
      bleeding, but declined additional APC therapy. No patient developed clinically
      evident progressive rectal wall abnormalities after APC, (post-APC follow-up
      range 4-13 months). CONCLUSIONS: Most patients benefited from APC, and no cases
      of clinically evident progressive tissue destruction were noted. Although APC
      appears to be efficacious and safe in the setting of the rectal doses described
      here, caution is in order when contemplating APC for brachytherapy patients.

PMID- 11597804
TI  - Radiotherapy for stage II testicular seminoma.
AB  - PURPOSE: To compare the outcome of patients with Stage II seminoma treated with
      prophylactic mediastinal irradiation, without any supradiaphragmatic irradiation,
      and with prophylactic left supraclavicular irradiation (PLSCI). METHODS AND
      MATERIALS: Between 1960 and 1999, 73 men with Stage II seminoma received
      postorchiectomy radiotherapy. Before 1984, 36 received prophylactic mediastinal
      irradiation (Series I); between 1984 and 1992, 17 received no supradiaphragmatic
      irradiation (Series II); and after 1992, 20 received PLSCI (Series III). The
      outcomes in these series were compared. RESULTS: The abdominal tumor sizes were
      as follows: Series I, <or=2 cm, n = 4; >2 and <or=5 cm, n = 12; >5 and <or=10 cm,
      n = 16; Series II, <or=2 cm, n = 1; >2 and <or=5 cm, n = 12; >5 and <or=10 cm, n
      = 4; and Series III, <or=2 cm, n = 1; >2 and <or=5 cm, n = 14; >5 and <or=10 cm,
      n = 5 (p = 0.75). The median duration of follow-up was 14.4, 9.3, and 4.5 years
      for Series I, II, and III, respectively. The 6-year freedom from relapse was 94%,
      71%, and 95% for Series I, II, and III, respectively. The differences between
      Series I and II (p = 0.014) and between II and III (p = 0.042) were significant.
      Three patients in Series II had a relapse in their left supraclavicular fossa-a
      failure pattern abrogated by PLSCI. CONCLUSIONS: PLSCI significantly diminishes
      the likelihood of relapse for Stage IIA, IIB, and IIC seminoma (mass <or=10 cm).

PMID- 11597805
TI  - Radiation-induced pulmonary toxicity: a dose-volume histogram analysis in 201
      patients with lung cancer.
AB  - PURPOSE: To relate lung dose-volume histogram-based factors to symptomatic
      radiation pneumonitis (RP) in patients with lung cancer undergoing 3-dimensional
      (3D) radiotherapy planning. METHODS AND MATERIALS: Between 1991 and 1999, 318
      patients with lung cancer received external beam radiotherapy (RT) with 3D
      planning tools at Duke University Medical Center. One hundred seventeen patients
      were not evaluated for RP because of <6 months of follow-up, development of
      progressive intrathoracic disease making scoring of pulmonary symptoms difficult,
      or unretrievable 3D dosimetry data. Thus, 201 patients were analyzed for RP.
      Univariate and multivariate analyses were performed to test the association
      between RP and dosimetric factors (i.e., mean lung dose, volume of lung receiving
      >or=30 Gy, and normal tissue complication probability derived from the Lyman and
      Kutcher models) and clinical factors, including tobacco use, age, sex,
      chemotherapy exposure, tumor site, pre-RT forced expiratory volume in 1 s, weight
      loss, and performance status. RESULTS: Thirty-nine patients (19%) developed RP.
      In the univariate analysis, all dosimetric factors (i.e., mean lung dose, volume
      of lung receiving >or=30 Gy, and normal tissue complication probability) were
      associated with RP (p range 0.006-0.003). Of the clinical factors, ongoing
      tobacco use at the time of referral for RT was associated with fewer cases of RP
      (p = 0.05). These factors were also independently associated with RP according to
      the multivariate analysis (p = 0.001). Models predictive for RP based on
      dosimetric factors only, or on a combination with the influence of tobacco use,
      had a concordance of 64% and 68%, respectively. CONCLUSIONS: Dosimetric factors
      were the best predictors of symptomatic RP after external beam RT for lung
      cancer. Multivariate models that also include clinical variables were slightly
      more predictive.

PMID- 11597806
TI  - Induction chemotherapy plus three-dimensional conformal radiation therapy in the
      definitive treatment of locally advanced non-small-cell lung cancer.
AB  - PURPOSE: To evaluate our institution's experience using chemotherapy in
      conjunction with three-dimensional conformal radiation therapy (3D-CRT). METHODS
      AND MATERIALS: From 1991 to 1998, 152 patients with Stage III non-small-cell lung
      cancer (NSCLC) were treated with 3D-CRT at Memorial Sloan-Kettering Cancer
      Center. A total of 137 patients (90%) were surgically staged with either
      thoracotomy or mediastinoscopy. The remainder were staged radiographically.
      Seventy patients were treated with radiation therapy alone, and 82 patients
      received induction chemotherapy before radiation. The majority of chemotherapy
      treated patients received a platinum-containing regimen. Radiation was delivered
      with a 3D conformal technique using CT-based treatment planning. The median dose
      in the radiation alone group was 70.2 Gy, while in the combined modality group,
      it was 64.8 Gy. RESULTS: The median follow-up time was 30.5 months among
      survivors. Stage IIIB disease was present in 36 patients (51%) in the radiation
      alone group and 57 patients (70%) in the combined-modality group. Thirty-nine
      patients had poor prognostic factors (KPS < 70 or weight loss > 5%), and they
      were equally distributed between the two groups. The median survival times for
      the radiation-alone and the combined-modality groups were 11.7 months and 18.1
      months, respectively (p = 0.001). The 2-year rates of local control in the
      radiation-alone and combined-modality groups were 35.4% and 43.1%, respectively
      (p = 0.1). Grade 3 or worse nonhematologic toxicity occurred in 20% of the
      patients receiving radiation alone and in 16% of those receiving chemotherapy and
      radiation. Overall, there were only 4 cases of Grade 3 or worse esophagitis.
      CONCLUSION: Despite more Stage IIIB patients in the combined-modality group, the
      addition of chemotherapy to 3D-CRT produced a survival advantage over 3D-CRT
      alone in Stage III NSCLC without a concomitant increase in toxicity. Chemotherapy
      thus appears to be beneficial, even in patients who are receiving higher doses of
      radiation therapy than are typically given with conventional techniques. Because
      locoregional failure remains a major challenge in patients with advanced disease,
      3D-CRT in conjunction with chemotherapy may allow safe treatment to the dose
      levels required to further enhance local control.

PMID- 11597807
TI  - Computed tomography-guided frameless stereotactic radiotherapy for stage I non
      small cell lung cancer: a 5-year experience.
AB  - PURPOSE: Stereotactic radiotherapy (SRT) is highly effective for brain metastases
      from non-small-cell lung cancers (NSCLCs). As such, primary lesions of NSCLC may
      also be treated effectively by similar focal high-dose SRT. METHODS AND
      MATERIALS: Between October 1994 and June 1999, 50 patients with pathologically
      proven T1-2N0 M0 NSCLC were treated by CT-guided frameless SRT. Of these, 21
      patients were medically inoperable and the remainder were medically operable but
      refused surgery. In most patients, SRT was 50-60 Gy in 5-10 fractions for 1-2
      weeks. Eighteen patients also received conventional radiotherapy of 40-60 Gy in
      20-33 fractions before SRT. RESULTS: With a median follow-up period of 36 months
      (range 22-66), 30 patients were alive and disease free, 3 were alive with
      disease, 6 had died of disease, and 11 had died intercurrently. Local progression
      was not observed on follow-up CT scans in 47 (94%) of 50 patients. The 3-year
      overall survival rate was 66% in all 50 patients and 86% in the 29 medically
      operable patients. The 3-year cause-specific survival rate of all 50 patients was
      88%. No definite adverse effects related to SRT were noted, except for 2 patients
      with a minor bone fracture and 6 patients with temporary pleural pain.
      CONCLUSIONS: SRT is a very safe and effective treatment for Stage I NSCLC.
      Additional studies involving a larger patient population and longer follow-up
      periods are warranted to assess this new treatment for early-stage lung cancer.

PMID- 11597808
TI  - Relationship of sentinel and axillary level I-II lymph nodes to tangential fields
      used in breast irradiation.
AB  - PURPOSE: To evaluate the volume of nodal irradiation associated with breast
      conserving therapy, we defined the anatomic relationship of sentinel lymph nodes
      and axillary level I and II lymph nodes in patients receiving tangential breast
      irradiation. METHODS AND MATERIALS: A retrospective analysis of 65 simulation
      fields in women with breast cancer treated with sentinel lymph node surgery and
      39 women in whom radiopaque clips demarcated the extent of axillary lymph node
      dissection was performed. We measured the relationship of the surgical clips to
      the anatomic landmarks and calculated the percentage of prescribed dose delivered
      to the sentinel lymph node region. RESULTS: A cranial field edge 2.0 cm below the
      humeral head the sentinel lymph node region was included or at the field edge in
      95% of the cases and the entire extent of axillary I and II dissection in 43% of
      the axillary dissection cases. In the remaining 57%, this field border
      encompassed an average of 80% of cranial/caudal extent of axillary level I and II
      dissection. In 98.5% of the cases, all sentinel lymph nodes were anterior to the
      deep field edge and 71% were anterior to the chest wall-interface, whereas 61% of
      the axillary dissection cohort had extension deep to the chest wall-lung
      interface. If the deep field edge had been set 2 cm below the chest wall-lung
      interface, the entire axillary dissection would have been included in 82% of the
      cases, and the entire sentinel lymph node would have been covered with a 0.5-cm
      margin. The median dose to the sentinel lymph node region was 98% of the
      prescribed dose. CONCLUSIONS: By extending the cranial border to 2 cm below the
      humeral head and 2 cm deep to the chest wall-lung interface, the radiotherapy
      fields used to treat the breast can include the sentinel lymph node region and
      most of axillary levels I and II.

PMID- 11597809
TI  - Second cancers after conservative surgery and radiation for stages I-II breast
      cancer: identifying a subset of women at increased risk.
AB  - PURPOSE: To assess the risk and patterns of second malignancy in a group of women
      treated with conservative surgery and radiation in a relatively contemporary
      manner for early-stage invasive breast cancer, and to identify a subgroup of
      these women at increased risk for a second cancer. METHODS AND MATERIALS: From
      1978 to 1994, 1,253 women with unilateral Stage I-II breast cancer underwent wide
      excision, axillary dissection, and radiation. The median follow-up was 8.9 years,
      with 446 patients followed for >or= 10 years. The median age was 55 years. Sixty
      eight percent had T1 tumors and 74% were axillary-node negative. Radiation was
      directed to the breast only in 78%. Adjuvant therapy consisted of chemotherapy in
      19%, tamoxifen in 19%, and both in 8%. Factors analyzed for their association
      with the cumulative incidence of all second malignancies, contralateral breast
      cancer, and non-breast cancer malignancy were: age, menopausal status, race,
      family history, obesity, smoking, tumor size, location, histology, pathologic
      nodal status, region(s) treated with radiation, and the use and type of adjuvant
      therapy. RESULTS: One hundred seventy-six women developed a second malignancy (87
      contralateral breast cancers at a median interval of 5.8 years, and 98 non-breast
      cancer malignancies at a median interval of 7.2 years). Nine women had both a
      contralateral breast cancer and non-breast cancer second malignancy. The 5- and
      10-year cumulative incidences of a second malignancy were 5% and 16% for all
      cancers, 3% and 7% for contralateral breast cancer, 3% and 8%, for all second non
      breast cancer malignancies, and 1% and 5%, respectively, for second non-breast
      cancer malignancies, excluding skin cancers. Patient age was a significant factor
      for contralateral breast cancer and non-breast cancer second malignancy. Young
      age was associated with an increased risk of contralateral breast cancer, while
      older age was associated with an increased the risk of a second non-breast cancer
      second malignancy. A positive family history increased the risk of contralateral
      breast cancer, but not non-breast cancer malignancies. The risk of a
      contralateral breast cancer increased as the number of affected relatives
      increased. Tamoxifen resulted in a nonsignificant decrease in contralateral
      breast cancer and an increase in non-breast cancer second malignancies. The 5-and
      10-year cumulative incidences for leukemia and lung cancer were 0.08% and 0.2%,
      and 0.8% and 1%, respectively. There was no significant effect of chemotherapy or
      the regions treated with radiation on contralateral breast cancer or non-breast
      cancer second malignancy. The most common types of second non-breast cancer
      malignancies were skin cancers, followed by gynecologic malignancies
      (endometrial), and gastrointestinal malignancies (colorectal and pancreas).
      CONCLUSION: The 10-years cumulative incidence of a second cancer in this study
      was 16%. Young age and family history predicted for an increased risk of
      contralateral breast cancer, and older age predicted for an increased risk of non
      breast cancer malignancy. The majority of patients treated with conservative
      surgery and radiation with or without adjuvant systemic therapy will not develop
      a second cancer. Long-term follow-up is important to document the risk and
      patterns of second cancer, and knowledge of this risk and the patterns will
      influence surveillance and prevention strategies.

PMID- 11597810
TI  - Fatigue, serum cytokine levels, and blood cell counts during radiotherapy of
      patients with breast cancer.
AB  - PURPOSE: To assess the level of fatigue during the course of adjuvant
      radiotherapy (RT) of breast cancer patients and its relation to anxiety,
      depression, serum cytokines, and blood count levels. METHODS AND MATERIALS: Forty
      one patients who received adjuvant RT after breast-conserving surgery were
      prospectively studied. All patients underwent RT without concomitant
      chemotherapy. Patients rated their fatigue with two standardized self-assessment
      instruments, the Fatigue Assessment Questionnaire and a visual analog scale on
      fatigue intensity, before RT, during weeks 1-5 of RT, and 2 months after RT
      completion. In addition, the anxiety and depression levels were assessed with the
      Hospital Anxiety and Depression Scale. A differential blood cell count and the
      serum levels of the cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis
      factor-alpha were determined in parallel to the fatigue assessments. RESULTS:
      Fatigue intensity as assessed with the visual analog scale increased (p <0.001)
      until treatment week 4 and remained elevated until week 5. Two months after RT,
      the values had fallen to the pretreatment levels. Fatigue measured with the
      Fatigue Assessment Questionnaire did not increase significantly during treatment,
      but the subscores on physical (p = 0.035) and cognitive (p = 0.015) fatigue were
      elevated during treatment weeks 4 and 5. Affective fatigue did not change
      significantly. Anxiety, as rated with the Hospital Anxiety and Depression Scale,
      declined during RT (p = 0.002), but the Hospital Anxiety and Depression Scale
      depression score did not change significantly. IL-1beta, IL-6, and tumor necrosis
      factor-alpha levels did not change during therapy and did not correlate with
      fatigue. Peripheral blood cell levels declined significantly during therapy and
      were still low 2 months after treatment. Until treatment week 5, lymphocytes were
      reduced to almost 50% of their initial values. Hemoglobin levels did not
      correlate with fatigue. CONCLUSIONS: We observed an increase in fatigue during
      adjuvant RT of patients with breast cancer. Fatigue returned to pretreatment
      levels 2 months after treatment. No evidence was found that anxiety, depression,
      serum levels of IL-1beta, IL-6, tumor necrosis factor-alpha, or declining
      hemoglobin levels were responsible for the treatment-induced fatigue.

PMID- 11597811
TI  - Tumor size and oxygenation are independent predictors of nodal diseases in
      patients with cervix cancer.
AB  - PURPOSE: To determine the relationships between tumor oxygenation and nodal stage
      in a prospective study of patients with cervix cancer, controlling for other
      prognostic factors. METHODS AND MATERIALS: Between 1994 and 1999, 128 eligible
      patients with cervix cancer were entered into a prospective study of tumor
      oxygenation assessed by Eppendorf oxygen electrode before primary radiation
      therapy. Oxygenation was evaluated using the proportion of pO(2) values < 5 mmHg
      (HP(5)), and tumors were classified as hypoxic if the HP(5) was > 50%. Patients
      were assigned to one of three groups: those with no imaging evidence of nodal
      (pelvic or para-aortic) or distant metastatic disease (N group; n = 67), those
      with equivocal findings (E group; n = 28), and those with nodal or distant
      metastatic disease (P group; n = 33). RESULTS: The proportion of hypoxic tumors
      in the P, E, and N groups were 67%, 50%, and 40%, respectively (p = 0.014), with
      median HP(5) values of 63%, 48%, and 36%, respectively (p = 0.0024). In a
      multivariate analysis including tumor size, stage, HP(5), and hemoglobin, it was
      found that tumor size and HP(5) were the only independently significant variables
      for the finding of metastatic disease (p = 0.009 and 0.017, respectively).
      CONCLUSION: In this patient population, there was a significantly increased risk
      of nodal or distant metastases in patients with hypoxic tumors, and this finding
      was independent of tumor size. These results are consistent with the hypothesis
      that tumor hypoxia is an adverse prognostic factor associated with selection for
      a metastatic phenotype.

PMID- 11597812
TI  - Results of a policy of surveillance alone after surgical management of pediatric
      low grade gliomas.
AB  - PURPOSE: To document the incidence of tumor progression in pediatric patients
      with low-grade gliomas (LGGs), with particular emphasis on those patients who did
      not receive postoperative chemotherapy or radiotherapy (RT). METHODS AND
      MATERIALS: A database of 128 patients with histologically confirmed LGGs (World
      Health Organization Grade I-II), age <or=18 years, who had been referred to the
      London Regional Cancer Center and Dalhousie University between 1979 and 1995, was
      compiled. RESULTS: The median follow-up for the 128 patients was 7.3 years. Of
      the 128 patients, 63 were male and 65 female. The median age was 7.0 years (range
      0-18). Twenty-five patients underwent gross complete resection, 63 subtotal
      resection, and 40 patients biopsy. Ninety-one percent (n = 117) of the tumors
      were astrocytomas, of which 22 were pilocytic, 3 were oligodendrogliomas, 7 were
      mixed gliomas, and 1 was a ganglioglioma. Of the 103 subtotally resected
      patients, 48 received postoperative RT (median dose 59 Gy in 25 fractions) and 10
      patients were irradiated at the time of tumor progression. The 5-year overall
      survival was 86%, cause-specific survival 88%, and 5-year progression-free
      survival 79%. The results of the univariate analysis of the overall survival by
      the Wilcoxon model were statistically significant for Karnofsky performance
      status (p = 0.03), RT timing (i.e., postoperative vs. deferred; p = 0.05), and
      tumor location (p = 0.02). The analysis of progression-free survival confirmed
      the statistical significance of the extent of surgical resection (i.e., complete
      vs. subtotal resection; p = 0.02). None of the patients who underwent gross
      complete resections received postoperative RT and none developed tumor
      recurrence. Of the 103 patients who had subtotal resections, 33 had progression,
      with a median postprogression survival of 39 months. The rate of tumor
      progression among the subtotally resected LGG patients who did not receive
      immediate postoperative RT was 42%. The timing of RT and tumor location lost
      statistical significance for overall survival when the completely resected
      patients were excluded from the analysis. CONCLUSIONS: The extent of surgical
      resection was prognostically significant for progression-free survival but lost
      significance as a prognostic factor once the complete resection patients were
      excluded from the analysis. At a median survival of 7.3 years, 42% of the
      subtotally resected LGG patients who did not receive immediate postoperative RT
      had tumor progression. No statistically significant difference in survival was
      seen between the postoperative and deferred RT groups, even though the
      postoperative RT group was a group with poorer prognostic features (bulky
      residual tumor postoperatively, Karnofsky performance status <70, and
      nonhemispheric, noncerebellar tumors), indicating that RT may be beneficial for
      this particular subset of patients.

PMID- 11597813
TI  - Neurocognitive outcome in brain metastases patients treated with accelerated
      fractionation vs. accelerated-hyperfractionated radiotherapy: an analysis from
      Radiation Therapy Oncology Group Study 91-04.
AB  - PURPOSE: To evaluate neurocognitive outcome as measured by the Mini-Mental Status
      Examination (MMSE) among patients with unresectable brain metastases randomly
      assigned to accelerated fractionation (AF) vs. accelerated hyperfractionated (AH)
      whole-brain radiation therapy (WBRT). METHODS AND MATERIALS: The Radiation
      Therapy Oncology Group (RTOG) accrued 445 patients with unresectable brain
      metastases to a Phase III comparison of AH (1.6 Gy b.i.d. to 54.4 Gy) vs. AF (3
      Gy q.d. to 30 Gy). All had a KPS of >or= 70 and a neurologic function status of 0
      2. Three hundred fifty-nine patients had MMSEs performed and were eligible for
      this analysis. Changes in the MMSE were analyzed according to criteria previously
      defined in the literature. RESULTS: The median survival was 4.5 months for both
      arms. The average change in MMSE at 2 and 3 months was a drop of 1.4 and 1.1,
      respectively, in the AF arm as compared to a drop of 0.7 and 1.3, respectively,
      in the AH arm (p = NS). Overall, 91 patients at 2 months and 23 patients at 3
      months had both follow-up MMSE and computed tomography/magnetic resonance imaging
      documentation of the status of their brain metastases. When an analysis was
      performed taking into account control of brain metastases, a significant effect
      on MMSE was observed with time and associated proportional increase in
      uncontrolled brain metastases. At 2 months, the average change in MMSE score was
      a drop of 0.6 for those whose brain metastases were radiologically controlled as
      compared to a drop of 1.9 for those with uncontrolled brain metastases (p =
      0.47). At 3 months, the average change in MMSE score was a drop of 0.5 for those
      whose brain metastases were radiologically controlled as compared to a drop of
      6.3 for those with uncontrolled brain metastases (p = 0.02). CONCLUSION: Use of
      AH as compared to AF-WBRT was not associated with a significant difference in
      neurocognitive function as measured by MMSE in this patient population with
      unresectable brain metastases and limited survival. However, control of brain
      metastases had a significant impact on MMSE.

PMID- 11597814
TI  - Results from the IRS-IV randomized trial of hyperfractionated radiotherapy in
      children with rhabdomyosarcoma--a report from the IRSG.
AB  - PURPOSE: To evaluate the outcome and toxicity of hyperfractionated radiotherapy
      (HFRT) vs. conventionally fractionated radiotherapy (CFRT) in children with Group
      III rhabdomyosarcoma (RMS). METHODS AND MATERIALS: Five hundred fifty-nine
      children were enrolled into the Intergroup Rhabdomyosarcoma Study IV with Group
      III RMS. Sixty-nine were ineligible for the analysis because of incorrect group
      or pathologic findings. Of the 490 remaining, 239 were randomized to HFRT (59.4
      Gy in 54 1.1-Gy twice daily fractions) and 251 to CFRT (50.4 Gy in 28 1.8-Gy
      daily fractions). The age range was <1-21 years. All patients received
      chemotherapy. RT began at Week 9 after induction chemotherapy for all but those
      with high-risk parameningeal tumors who received RT during induction
      chemotherapy. The patient groups were equally balanced. The median follow-up was
      3.9 years. RESULTS: Analysis by randomized treatment assignment (intent to treat)
      revealed an estimated 5-year failure-free survival (FFS) rate of 70% and overall
      survival (OS) of 75%. In the univariate analysis, the factors associated with the
      best outcome were age 1-9 years at diagnosis; noninvasive tumors; tumor size <5
      cm; uninvolved lymph nodes; Stage 1 or 2 disease; primary site in the orbit or
      head and neck; and embryonal histologic features (p = 0.001 for all factors). No
      differences in the FFS or OS between the two RT treatment methods and no
      differences in the FFS or OS between HFRT and CFRT were found when analyzed by
      age, gender, tumor size, tumor invasiveness, nodal status, histologic features,
      stage, or primary site. Treatment compliance differed by age. Of the children <5
      years, 57% assigned to HFRT received HFRT and 77% assigned to CFRT received CFRT.
      Of the children >or=5 years, 88% assigned to both HFRT and CFRT received their
      assigned treatment. The reasons for not receiving the appropriate randomized
      treatment were progressive disease, early death, parent or physician refusal,
      young age, or surgery. The toxicity assessment revealed more mucositis with HFRT
      (66%) than with CFRT (46%) (p = 0.03) for the parameningeal patients, and more
      skin reactions (16%) and nausea/vomiting (13%) with HFRT than with CFRT (7% and
      5%, respectively) for patients with nonparameningeal primary tumors (p = 0.03 and
      p = 0.02, respectively). The analysis by treatment actually received revealed a 5
      year FFS rate of 73% and OS rate of 77%, with no difference between CFRT and
      HFRT. As well, there was no difference in FFS or OS between CFRT and HFRT when
      analyzed by age, gender, tumor size, tumor invasiveness, modal status, histology,
      stage or site of primary. The 5-year estimated cumulative incidence of failure
      for the irradiated patients was local, 13%; regional, 3%; and distant, 13%; with
      no differences between HFRT and CFRT. The 5-year local failure rate by site was
      orbit, 5%; head and neck, 12%; parameningeal, 16%; bladder/prostate, 19%;
      extremity, 7%; and all others, 14%. The 5-year regional failure rate was
      parameningeal,1%; extremity, 20%; and all others, 5%. The 5-year distant failure
      rate was orbit, 2%; head and neck, 6%; parameningeal, 11%; bladder/prostate, 15%;
      extremity, 28%; and all others, 17%. CONCLUSIONS: HFRT, as given in this study,
      did not improve local/regional control, FFS, or OS compared with CFRT. The risk
      of local/regional failure was comparable to that of distant failure in children
      with Group III RMS. The standard of care for Group III RMS continues to be CFRT
      with chemotherapy.

PMID- 11597815
TI  - Intraoperative high-dose-rate brachytherapy for the treatment of pediatric
      tumors: the Ohio State University experience.
AB  - PURPOSE: To determine whether intraoperative high-dose-rate brachytherapy (IO
      HDRBT) can be used to decrease the dose of external beam radiotherapy (EBRT) in
      the treatment of children with soft-tissue sarcomas and, thereby, reduce
      morbidity without compromising local control. METHODS AND MATERIALS: From March
      1992 through April 1999, 13 pediatric patients were treated with IO-HDRBT, low
      dose EBRT, chemotherapy, and radical surgery at 21 sites that were not amenable
      to intraoperative electron beam therapy. The IO-HDRBT dose at 5 mm depth was 10
      to 12.5 Gy for close margins/microscopic disease at 14 sites and 12.5 to 15 Gy
      for gross disease at 7 sites. The treatment volumes ranged from 4 to 96 cm(3)
      (mean 27). The EBRT dose was limited to 27-30 Gy in most cases to minimize growth
      retardation and preserve normal organ function. RESULTS: After a median follow-up
      of 47 months (range 12-97), 11 patients were alive and without evidence of
      disease (overall survival rate 85%, 4-year actuarial survival rate 77%). Of the 2
      who died, 1 had Stage III pulmonary blastoma with a sacral recurrence; the other
      had Stage IV undifferentiated synovial sarcoma with a pulmonary recurrence. One
      local failure occurred in a patient with gross residual disease after incomplete
      resection for Stage IV pulmonary blastoma. The local control rate was 95%, and
      morbidity was observed in 3 patients (23%). One patient developed impaired
      orbital growth with mild ptosis. Another patient required orthopedic pinning of
      her femoral subcapital epiphysis and construction of a neobladder secondary to
      urethral obstruction. The third patient required reimplantation of her
      autotransplanted kidney secondary to chronic urinary tract infection and ureteral
      reflux. CONCLUSIONS: IO-HDRBT allowed for reduction in EBRT without compromising
      local control or disease-free survival in children with soft-tissue sarcomas.
      Tumor beds inaccessible to electron beam methods could be satisfactorily
      encompassed with IO-HDRBT techniques.

PMID- 11597816
TI  - Radiotherapy and continuous infusion 5-fluorouracil in patients with
      nonresectable pancreatic carcinoma.
AB  - PURPOSE: The current standard local treatment for nonresectable pancreatic
      carcinoma is radiotherapy (RT) with concurrent 5-fluorouracil (5-FU); however,
      the optimal schedule for 5-FU administration has not been fully established. In
      this study, we report on our experience with the combination of RT and continuous
      infusion 5-FU in a group of patients with locally nonresectable pancreatic
      carcinoma. METHODS AND MATERIALS: Forty-two patients with adenocarcinoma of the
      pancreas were enrolled in a prospective clinical trial. RT was delivered using a
      four-field technique to a total dose of 59.4 Gy in 33 fractions. 5-FU was given
      through a central venous catheter at a dose of 300 mg/m(2)/day, 7 d/wk,
      throughout the entire course of RT. RESULTS: All patients completed the RT as
      planned, and 33 (78%) completed the full regimen of chemotherapy. Ten patients
      (23%) had a partial response, and 32 (77%) had stable disease. Subjective
      response, defined as the disappearance of symptoms observed at diagnosis, was
      also evaluated. Two patients (6%) had a complete, and 24 (75%) a partial,
      remission of symptoms. The median time to progression was 6.2 months, and the
      median survival time was 9.1 months. CONCLUSIONS: In terms of local control, the
      results of our study, with RT and protracted 5-FU infusion, compare well with
      those of other studies using RT and bolus 5-FU. The control of distant metastatic
      disease remains an open issue. However, the palliation of symptoms achieved by
      our treatment schedule in patients with a very poor prognosis and severe symptoms
      may be regarded as a positive result.

PMID- 11597817
TI  - Elective groin irradiation is not indicated for patients with adenocarcinoma of
      the rectum extending to the anal canal.
AB  - PURPOSE: To evaluate the inguinal nodal failure rate in patients with locally
      advanced rectal cancer with anal canal involvement (ACI) treated with pelvic
      chemoradiation without elective inguinal irradiation. METHODS AND MATERIALS: From
      1990 and 1998, 536 patients received preoperative or postoperative chemoradiation
      for rectal cancer with curative intent; 186 patients had ACI (<4 cm from the anal
      verge on rigid proctoscopy). Two patients had positive inguinal nodes at
      presentation. Chemoradiation was delivered preoperatively (45 Gy in 25 fraction)
      or postoperatively (53 Gy in 29 fractions) with concurrent continuous infusion of
      5-fluorouracil (300 mg/m2/d). The inguinal region was specifically irradiated in
      only 2 patients who had documented inguinal nodal disease. RESULTS: The median
      follow-up was 50 months. Only 6 of 184 ACI patients who had clinically negative
      inguinal nodes at presentation developed inguinal nodal recurrence (5-year
      actuarial rate 4%); 4 of the 6 cases were isolated. Two patients underwent
      successful salvage. Only 1 died of uncontrolled groin disease. Local control was
      achieved in both patients with inguinal nodal disease at presentation, but both
      died of metastatic disease. Only 3 patients with tumors >4 cm from the verge
      developed inguinal recurrence (5-year actuarial rate <1%). CONCLUSIONS: Inguinal
      nodal failure in rectal cancer patients with ACI treated with neoadjuvant or
      adjuvant chemoradiation is not high enough to justify routine elective groin
      irradiation.

PMID- 11597818
TI  - Different effects of antipsychotic drugs on insulin release in vitro.
AB  - The aim of this study was to examine the influence of antipsychotic drugs on
      insulin release from pancreatic beta cells in vitro. The effect of seven
      antipsychotics (i.e. chlorpromazine, haloperidol, perphenazine, zuclopenthixol,
      clozapine, olanzapine and risperidone) in a concentration of 10(-6) M was
      investigated on basal and glucose-stimulated insulin release. Clozapine increased
      basal insulin release, whereas haloperidol inhibited glucose-stimulated release
      and the other five antipsychotics had no significant effects. A possible
      stimulatory effect of clozapine on insulin release may explain its ability to
      increase appetite and induce weight gain.

PMID- 11597819
TI  - The effects of citicoline and/or MK-801 on survival, neurological and behavioral
      outcome of mice exposed to transient hyperglycemia and oligemic hypoxia.
AB  - The effects of citicoline and/or low dose of MK-801 (sufficient to prevent the
      development of seizures) on survival, neurological and behavioral recovery
      following transient hyperglycemic-oligemic-hypoxic insult have been evaluated in
      mice. Neurological recovery was assessed semi-quantitatively on the third and the
      10th day after the insult, and behavioral tests evaluating spontaneous locomotor
      activity, motor coordination and spontaneous alternation performance were
      performed on day 10. Neither drug given alone did influence survival rate, but
      the combination of MK-801 and higher citicoline dose decreased mortality on day
      10. Behavioral performance was markedly compromised by the insult. Citicoline,
      but not MK-801, slightly but significantly improved behavioral outcome in all
      three tests. CONCLUSION: when brain ischemic insult is complicated with acute
      hyperglycemia, post-treatment with citicoline combined with MK-801 in low anti
      convulsive dose improves survival and neurological recovery, and citicoline but
      not MK-801 enhances behavioral recovery.

PMID- 11597820
TI  - Prevention of the stress-induced increase in frontal cortical dopamine efflux of
      freely moving rats by long-term treatment with antidepressant drugs.
AB  - Use of antidepressant drugs in the treatment of anxiety disorders has recently
      increased due to the anxiolytic effect of some of these agents. Because
      dopaminergic transmission in the prefrontal cortex is sensitive to anxiogenic or
      stressful stimuli, the effects of two antidepressant drugs with different
      mechanisms of action, imipramine and mirtazapine, on the response of rat cortical
      dopaminergic neurons to stress were investigated. A 2-week (but not single dose)
      administration of imipramine (10 mg/kg, i.p., twice daily) or mirtazapine (10
      mg/kg, i.p., once daily) reduced and completely antagonized, respectively, the
      increase in dopamine release in the prefrontal cortex elicited by footshock
      stress. Long-term administration of imipramine or mirtazapine had no marked
      effect on the stress-induced increases in the brain or plasma concentrations of
      neuroactive steroids or corticosterone. An attenuation of the response of
      mesocortical dopaminergic neurons to stress induced by long-term treatment with
      antidepressants might contribute to the anxiolytic effects of such drugs.

PMID- 11597821
TI  - Antidepressant-like action of AGN 2979, a tryptophan hydroxylase activation
      inhibitor, in a chronic mild stress model of depression in rats.
AB  - Chronic mild stress (CMS) procedure was used to study an antidepressant-like
      activity of AGN 2979, a selective inhibitor of tryptophan hydroxylase (TH)
      activation. At the dose of 4 mg/kg, AGN 2979 fully reversed the CMS-induced
      reduction in the consumption of 1% sucrose solution. This effect was maintained
      for at least 1 week after cessation of treatment and no signs of withdrawal were
      observed in either stressed or control animals receiving AGN 2979. The lower (1
      mg/kg) and higher (16 mg/kg) doses were ineffective. The magnitude of action of
      AGN 2979 in the CMS model was comparable to that of imipramine (10 mg/kg) but its
      onset of action appears to be faster since the inhibition of sucrose intake in
      stressed animals was already reversed after the 1st week of AGN 2979
      administration while imipramine required 3 weeks of treatment to cause similar
      effect. These results provide support for the hypothesis that inhibition of TH
      activation may result in a potent antidepressant activity.

PMID- 11597822
TI  - Nicotine stimulation of dorsal raphe neurons: effects on laterodorsal and
      pedunculopontine neurons.
AB  - Previous studies showed that nicotine suppresses the ponto-geniculo-occipital
      (PGO) spikes of rapid eye movement (REM) sleep in cats. This effect may depend on
      stimulation of dorsal raphe nucleus (DRN) serotoninergic neurons that inhibit the
      pedunculopontine (PPT) and laterodorsal tegmental (LDT) cholinergic neurons,
      generators of PGO spikes. For testing this hypothesis 37 experiments were
      performed in rat midbrain slices. Nicotine (2 mM), administered locally into DRN,
      significantly increased the firing rate of 81.1% DRN neurons and serotonin
      release while simultaneously and significantly decreasing the firing rate of
      80.8% LDT neurons and of 81.8% PPT neurons. The inhibition of LDT neurons by
      nicotine administered into DRN was blocked by the 5-HT1A receptor antagonist WAY
      100635 (140 nM) administered into LDT. These results indicate that nicotine
      inhibits the activity of LDT and PPT neurons and consequently the generation of
      PGO spikes through stimulation of DRN serotoninergic neurons.

PMID- 11597824
TI  - Tryptophan hydroxylase gene associated with paroxetine antidepressant activity.
AB  - The possible association of the A218C tryptophan hydroxylase (TPH) gene variant
      with the antidepressant activity of paroxetine was investigated in a sample of
      121 inpatients affected by a major depressive episode and treated with paroxetine
      20-40 mg with either placebo or pindolol in a double blind design for 4 weeks.
      The severity of depressive symptoms was weekly assessed with the Hamilton Rating
      Scale for Depression. TPH allelic variants were determined in each subject using
      a PCR-based technique. TPH*A/A and TPH*A/C variants were associated with a poorer
      response to paroxetine treatment when compared to TPH*C/C (P=0.005); this
      difference was not present in the pindolol augmented group. Other variables, such
      as sex, diagnosis, presence of psychotic features, severity of depressive
      symptomatology at baseline and paroxetine plasma level, were not associated with
      the outcome. TPH gene variants are therefore a possible modulator of paroxetine
      antidepressant activity.

PMID- 11597823
TI  - Brain maldevelopment and neurobehavioural deviations in adult rats treated
      neonatally with indomethacin.
AB  - The risk of neurodevelopmental toxicity was studied in indomethacin (INDO), an
      inhibitor of prostaglandin synthesis, which is used in at-risk neonates to
      prevent the consequences of brain intraventricular haemorrhage or to accelerate
      the closure of patent ductus arteriosus. Model experiments were carried out in
      rats of the Wistar strain and Konarovice breed. The drug dose (2 mg/kg, s.c.) was
      applied to rat pups either once or twice in the following way: (1) on postnatal
      day 4 (PD:4) or postnatal days 4 and 5 (PD:4-5), i.e. model of brain ontogenic
      developmental stage in human fetus/preterm neonate of 7-month-gestational age;
      (2) on postnatal day 9 (PD:9) or postnatal days 9-10 (PD:9-10), i.e. model of
      brain ontogenic stage in full-term human newborn. The rats were followed up
      during development (body weight, maturation) until adulthood (age 3-9 months)
      using tests of behaviour (open field, social memory), nociception (tail flick,
      plantar test), reproduction and brain neurobiological analysis. The results were
      evaluated by comparison of litter-mates: treated vs control. No differences
      between INDO and controls were found in developmental landmarks, adult social
      memory or reproduction. The pattern of behavioural and neuroendocrine deviations
      in adult animals was dependent on the ontogenic stage exposed to drug insult.
      INDO rats of the groups PD:4 and PD:4-5 revealed depression of open field motor
      activity and emotional reactivity, and higher pituitary weight with lower TSH
      content. On the other hand, deviations in adult INDO groups PD:9 and PD:9-10 were
      characterized by pain hypersensitivity, lower pituitary weight with unchanged TSH
      content and deficit of monoamine transmission in the hypothalamus.

PMID- 11597825
TI  - Acetylcholinesterase inhibitor SDZ ENA 713 (Rivastigmine) increases brain
      pyrrolidone carboxyl peptidase activity.
AB  - Pyroglutamyl-ended forms of amyloid-beta-peptide are present in senile plaques in
      some individuals with Alzheimer type dementia. Single oral administration of the
      acetylcholinesterase inhibitor SDZ ENA 713 (rivastigmine (+)-(S)-N-ethyl-3-[(1
      dimethylamino)ethyl]-N-methylphenylcarbamate hydrogen tartrate) increases basal
      and K(+)-stimulated pyrrolidone carboxyl peptidase (Pcp) activity in mice frontal
      cortex synaptosomes in a dose-dependent manner. These results suggest that this
      drug may ameliorate ATD cognitive deficits acting not only facilitating
      cholinergic transmission but also avoiding the formation of pyroglutamyl-ended
      amyloid-beta-peptides (A beta pE) deposition through the activation of Pcp.

PMID- 11597826
TI  - Urocortin protects against ischemic injury via a MAPK-dependent pathway.
AB  - Urocortin (UCN), is a peptide related to hypothalamic corticotrophin releasing
      hormone (CRF) and binds with high affinity to the CRF-R2 beta receptor which is
      expressed in the heart. UCN prevents cell death when administered to primary
      cardiac myocyte cultures both prior to simulated hypoxia/ischemia and at the
      point of reoxygenation after simulated hypoxia/ischemia as assayed by trypan blue
      exclusion. 3'-OH end labeling of DNA (TUNEL), annexin-V and fluorescence
      activated cell sorting. The protective effect of UCN is dependent on the p42/p44
      mitogen-activated protein kinase (MAPK)-pathway. UCN also reduces damage in
      isolated rat hearts ex vivo, subjected to regional ischemia/reperfusion with the
      protective effect being observed when UCN is given either prior to ischemia or at
      the time of reperfusion after ischemia. Hence, UCN is a cardioprotective agent,
      which acts when given prior to ischemia or after ischemia at reperfusion.

PMID- 11597827
TI  - Mechanisms of hepatic very low-density lipoprotein overproduction in insulin
      resistance.
AB  - An important complication of insulin-resistant states, such as obesity and type 2
      diabetes, is an atherogenic dyslipidemia profile characterized by
      hypertriglyceridemia, low plasma high-density lipoproteins (HDL) cholesterol and
      a small, dense low-density lipoprotein (LDL) particle profile. The physiological
      basis of this metabolic dyslipidemia appears to be hepatic overproduction of apoB
      containing very low-density lipoprotein (VLDL) particles. This has focused
      attention on the mechanisms that regulate VLDL secretion in insulin-resistant
      states. Recent studies in animal models of insulin resistance, particularly the
      fructose-fed hamster, have enhanced our understanding of these mechanisms, and
      certain key factors have recently been identified that play important roles in
      hepatic insulin resistance and dysregulation of the VLDL secretory process. This
      review focuses on these recent developments as well as on the hypothesis that an
      interaction between enhanced flux of free fatty acids from peripheral tissues to
      liver, chronic up-regulation of de novo lipogenesis by hyperinsulinemia and
      attenuated insulin signaling in the liver may be critical to the VLDL
      overproduction state observed in insulin resistance. It should be noted that the
      focus of this review is on molecular mechanisms of the hypertriglyceridemic state
      associated with insulin resistance and not that observed in association with
      insulin deficiency (e.g., in streptozotocin-treated animals), which appears to
      have a different etiology and is related to a catabolic defect rather than
      secretory overproduction of triglyceride-rich lipoproteins.

PMID- 11597828
TI  - Allocation and early differentiation of cardiovascular progenitors in the mouse
      embryo.
AB  - During gastrulation of the mouse embryo, progenitor cells of the endothelium of
      blood vessels are allocated to different compartments of the extraembryonic and
      embryonic tissues in accordance to the timing and the site of recruitment to the
      mesodermal layer. In the yolk sac, the endothelium and the erythropoietic
      progenitors are populated by different groups of mesodermal cells, suggesting
      that they may not be derived from a common pool of progenitors. An orderly
      pattern of movement of mesodermal cells and the provision of proper intercellular
      transforming growth factor beta (TGF beta) and vascular endothelial growth factor
      (VEGF) signaling by neighboring germ layer tissues are essential for normal
      morphogenesis of the vasculature.

PMID- 11597829
TI  - Conserved cardiogenic functions of the multitype zinc-finger proteins: U-shaped
      and FOG-2.
AB  - Multitype zinc-finger proteins murine Friend of GATA-2 (FOG-2) and Drosophila U
      shaped (Ush) are required for heart development. Both FOG proteins participate in
      signal transduction pathways that are essential for cardiogenesis. FOG-2
      regulates signaling from the myocardium, which is required for the production of
      the coronary vasculature. Ush functions in a common pathway with the Heartless
      (Htl) fibroblast growth factor (FGF) receptor to control mesodermal cell
      migration, which is required for cardiogenic cell fate commitment. In vitro
      studies have demonstrated that both FOG proteins repress GATA factor
      transcriptional activation of cardiac promoters. These similarities provide
      further evidence for the conservation of gene functions during cardiogenesis in
      Drosophila and higher eukaryotes.

PMID- 11597830
TI  - Analysis of patients treated with living pig tissue for evidence of infection by
      porcine endogenous retroviruses.
AB  - The use of pigs as a source of cells and organs for transplantation has the
      potential to reduce the current chronic shortage of organs for the treatment of
      many end-stage diseases. The risk of transmission of infectious agents across the
      species barrier (zoonoses) has to be assessed. Many such agents can be eliminated
      from the pig herd. However, porcine endogenous retroviruses, which are carried
      within the pig genome, are not easily eliminated. They can infect primary and
      immortalized human cells in vitro, but to date no evidence for in vivo infection
      has been found in retrospective studies of humans exposed to viable porcine
      cells. Small-scale clinical trials using porcine cells for the treatment of
      Parkinson's and Huntington's disease are currently in progress. The prospective
      monitoring of these patients in conjunction with further research into the
      biology of this virus will help address safety issues.

PMID- 11597831
TI  - Selective estrogen receptor modulators and coronary heart disease.
AB  - The vasculature has been recognized as an important target of estrogen action
      through rapid non-genomic effects and/or via the classic pathway (genomic
      effects) involving estrogen receptors (ER-alpha and ER-beta). Multiple mechanisms
      participate in the regulation of different estrogen-controlled genes, providing a
      wide spectrum of possibilities for development of drugs, including pure agonists
      or antagonists or mixed agonists/antagonists, the so-called selective estrogen
      receptor modulators (SERM). In theory, an ideal SERM should reduce the risks of
      coronary heart disease (CHD) and preserve bone density, without or with very low
      incidences of breast and endometrial neoplasms or venous thromboembolism (VTE).
      The precise mechanism for the protective effects of estrogens and their receptors
      on cardiovascular diseases is not yet fully established. In this review, we
      summarize the recent advances in understanding the action of ERs/ligands, the
      therapeutic implications for CHD, and highlight the recent progress of both
      clinical and basic studies on the protection issue. Finally, a number of newly
      developed SERMs and their clinical applications as well as the laboratory
      investigations are discussed.

PMID- 11597832
TI  - Matrix metalloproteinase inhibition and the prevention of heart failure.
AB  - Matrix metalloproteinases (MMPs) are members of a large family of enzymes that
      can degrade extracellular matrix as well as other molecules. MMPs participate in
      a broad variety of normal and pathologic states, and recent evidence implicates
      the MMP family as potential mediators of cardiac dilation and progression to
      heart failure. This evidence is based on several lines of investigation. First,
      members of the MMP family are overexpressed in the myocardium in both
      experimental and human myocardial injury, infarction, and dilation. Second,
      overexpression of at least one MMP (MMP-1) in the hearts of transgenic mice can
      cause cardiac hypertrophy, dilation, and systolic dysfunction. Third, studies
      from multiple laboratories with different experimental models indicate that
      inhibition of MMPs through small molecules or gene transfer of endogenous
      inhibitors favorably affects cardiac remodeling. Fourth, targeted deletion of MMP
      genes in mice attenuates cardiac remodeling. These compelling results appear to
      fulfill Koch's Postulates as they may be applied to a non-infectious mediator of
      a disease, and thus current evidence supports MMP inhibition as a promising
      strategy for preventing heart failure. However, the crucial question of whether
      MMP inhibition benefits long-term left ventricular function and survival should
      be answered.

PMID- 11597833
TI  - Altered regulation of cardiac muscle contraction by troponin T mutations that
      cause familial hypertrophic cardiomyopathy.
AB  - Mutations in cardiac Troponin T (TnT) are responsible for approximately 15% of
      all cases of familial hypertrophic cardiomyopathy (FHC). This review summarizes
      recent data from in vitro assays, transgenic models and clinical studies on how
      TnT mutations alter the regulation of cardiac muscle contraction. Each TnT
      mutation has somewhat different effects on myofilament properties (increased
      myofilament Ca(2)+ sensitivity, decreased maximal force, decreased binding
      affinity to the thin filament, impaired pH-regulation). But when the in vitro
      data are correlated with the results from the transgenic models, essentially all
      mutations can be predicted to result in: (1) impaired relaxation, (2) reduced
      diastolic compliance, (3) reduced contractile reserve, (4) preserved systolic
      function under baseline conditions, and (5) cardiac dysfunction under inotropic
      stimulation. Thus, the alterations of myofilament function caused by TnT
      mutations likely play an important role in the pathogenesis of FHC.

PMID- 11597834
TI  - More observations about the NICU.

PMID- 11597836
TI  - Chronic disease challenges present new opportunities for AAMC-CDC partnerships.
      Association of American Medical Colleges.

PMID- 11597837
TI  - America's best medical schools: a critique of the U.S. News & World Report
      rankings.
AB  - Rankings of American medical schools published annually by the news magazine U.S.
      News & World Report are widely used to judge the quality of the schools and their
      programs. The authors describe and then critique the rankings on methodologic and
      conceptual grounds, arguing that the annual U.S. News medical school evaluation
      falls short in both areas. Three categories of program quality indicators
      different from those used by U.S. News are presented as alternative ways to judge
      medical schools. The authors conclude that the annual U.S. News & World Report
      rankings of American medical schools are ill-conceived; are unscientific; are
      conducted poorly; ignore medical school accreditation; judge medical school
      quality from a narrow, elitist perspective; and do not consider social and
      professional outcomes in program quality calculations. The medical school
      rankings have no practical value and fail to meet standards of journalistic
      ethics.

PMID- 11597838
TI  - The present and future of appointment, tenure, and compensation policies for
      medical school clinical faculty.
AB  - The authors present data and information about appointment, tenure, and
      compensation policies to describe how medical schools are redefining the terms
      under which they relate to their full-time clinical faculties. First, the authors
      note the increasing differentiation of clinical faculty members into two groups,
      researchers and clinicians. The present-day competitive realities of both
      research and clinical enterprises have prompted this change and the principles of
      mission-based management are reinforcing it. Second, they document the long-term
      tendency of schools to appoint new clinical faculty members to contract-term (as
      opposed to tenure) appointments, as special non-tenure-eligible tracks for
      clinically oriented faculty proliferate. Third, they report on the policies of
      schools to limit the financial guarantees provided to clinical faculty members
      who are awarded tenure. For schools that have yet to address this issue, they
      discuss the various employment and pay arrangements that inform or confuse the
      question. Fourth, they describe historic problems with clinical faculty
      compensation arrangements and illustrate, with examples from ten schools, the
      characteristics of recently implemented performance- and risk-based compensation
      plans. While these trends in institutional policies and practices may initially
      concern faculty advocate groups, the authors argue that they may serve the long
      term interests of those groups. The terms of relationships between medical
      schools and their clinical faculties are tied closely to the specifics of
      organizational structure, which are currently undergoing review and change. The
      challenge all schools face is to define these terms in ways that allow them to
      continue to attract high-quality clinical faculty while avoiding an insupportable
      financial liability.

PMID- 11597839
TI  - Critical issues in PhD training for biomedical scientists.
AB  - The rapidly changing world of modern biomedical research is raising important new
      issues for traditional PhD training programs and is creating concern among young
      PhD scientists about their futures. Specifically, the United States is producing
      substantially more biomedical PhDs than can be accommodated in professional
      positions that truly require the PhD as a credential. The "surplus" PhD
      population is being relegated to poorly paid, unstable, and increasingly
      unsatisfying jobs. In addition, many current graduate and postdoctoral training
      programs may not be adequately preparing young scientists for the more complex,
      more quantitative biological science of the future. Finally, many current
      graduate training programs are not attracting a sufficient portion of the most
      talented young people in the nation. To ameliorate these problems in the training
      and early career paths of basic biomedical scientists, the authors make specific
      recommendations, such as urging (1) that graduate trainees should be supported
      exclusively by competitive individual fellowships, training grants, or
      institutional funds and not by RO1s or similar research awards; (2) that graduate
      and postdoctoral stipends be increased so that they provide a reasonable living
      wage; and (3) that research-intensive academic institutions create a career path
      for biomedical PhDs other than that designed for the traditional tenure-track,
      grant-funded principal investigator and faculty member. They conclude that it is
      in the interest of faculty and institutions to make these and other drastic
      changes because the current system is both inherently unfair and self
      destructive.

PMID- 11597840
TI  - How doctors learn: education and learning across the medical-school-to-practice
      trajectory.
AB  - People have needs they address daily over the course of their lives. They address
      these needs through identifying and resolving problems in ways that reflect their
      identities. This means that education, including medical education, is an
      identity development process because it provides people with more and better ways
      to satisfy their needs. Also, education does this by providing them with the
      knowledge and skills they use to occupy identifiable niches in society. These
      niches are describable in terms of what people do and the ways in which they
      relate to others. Medical education, in other words, allows medical students and
      residents to take on physicians' identities, and their identities go a long way
      toward defining when, where, and how they will address their psychosocial needs.
      Doctors begin developing the skills and knowledge they need in medical school and
      continue developing them through residency and into practice. However, there are
      important differences among medical students, residents, and practicing
      physicians, and these differences have an impact on how the individuals satisfy
      their psychosocial needs. These differences also bear on how well they will
      satisfy their needs later in their careers; i.e., the things physicians-in
      training do to satisfy their psychosocial needs in the course of learning to
      become doctors are expected to prepare them to address their psychosocial needs
      later in life in their roles as both healers and professionals. It is against
      this background of describing how education helps physicians solve problems and
      so address their recurring psychosocial needs that the author presents 12
      conclusions concerning physicians' learning.

PMID- 11597841
TI  - Learning disabilities and the meaning of medical education.

PMID- 11597842
TI  - Is this a way to choose a chair?

PMID- 11597843
TI  - Modern foreign language study in the premedical curriculum. 1951.

PMID- 11597844
TI  - Wanting to die.

PMID- 11597846
TI  - Correlates of young physicians' support for unionization to maintain professional
      influence.
AB  - PURPOSE: A resolution in support of physicians' unionization was recently
      approved by the American Medical Association's House of Delegates. This study
      investigated the factors associated with young physicians' approval of
      unionization. METHOD: A survey was mailed to all 1987-1992 Jefferson Medical
      College graduates (n = 1,272); 835 (66%) responded. RESULTS: Of the respondents,
      43% supported unionization, 31% did not support unionization, and 26% expressed
      no opinion. Surgeons, medical subspecialists, pediatricians, and hospital-based
      specialists were more likely to support unionization than were family physicians.
      Significant predictors of support for unionization were negative views of the
      changes in the health care system, negative perceptions of the quality of care
      provided by managed care, the belief that physicians' independence had been
      impaired by changes in the health care system, and the belief that physicians'
      personal satisfaction should take precedence over societal needs in determining
      the future of health care. Support for unionization correlated with physicians'
      perceptions that mental health patients should be referred to psychiatrists,
      physician-assisted suicide should be legalized, and the involvement of nurse
      practitioners in diagnosis and treatment could compromise the quality of care.
      CONCLUSIONS: Young physicians' support for unionization is a function of
      frustration with market-driven policies that compromise the quality of care and
      negatively affect physicians' autonomy and personal satisfaction.

PMID- 11597847
TI  - Changes in health care providers' knowledge, attitudes, beliefs, and behaviors
      regarding domestic violence, following a multifaceted intervention.
AB  - PURPOSE: To improve domestic violence (DV) identification, management, and
      referral in a not-for-profit rural health network, training for health care
      professionals was implemented using a train-the-trainer approach, two one-hour
      training sessions, and dissemination of a clinical protocol. The multifaceted
      approach also involved modifications of emergency department medical records,
      distribution of office enablers, and a local public health campaign. The authors
      measured the effectiveness of this campaign. METHODS: After implementation of a
      multifaceted training and public awareness campaign, a questionnaire designed by
      the Centers for Disease Control to measure knowledge, attitudes, beliefs, and
      intended behaviors (KABB) of health care providers relative to DV was
      administered to 380 health care professionals in the fall of 1997, with a follow
      up survey completed after the intervention in the fall of 1999. RESULTS: The
      response rates for the pre- and post-intervention surveys were 67% (n = 380) and
      56% (n = 273), respectively. Two scales were correlated in the base-line survey:
      self-efficacy (related to DV response) and familiarity with referral resources.
      Reporting of victim identification in the preceding year increased from 36% to
      39%. Those with training were more likely to have identified a victim within the
      year (OR = 2.86; 95% CI, 1.73-4.74). Among the 232 respondents with complete
      data, multiple analysis of variance demonstrated statistically significant
      overall improvement across all scales. Nine of the 13 KABB scales revealed
      significant increases from pre- to posttest and included: screening, workplace
      resources, making referrals, provider self-efficacy, victim autonomy, victim
      understanding, legal requirements, staff preparation, and too busy/can't help.
      CONCLUSION: A comprehensive training program for health care providers can
      increase their self-efficacy in responding to DV victims.

PMID- 11597848
TI  - A comparison of global ratings and checklist scores from an undergraduate
      assessment using an anesthesia simulator.
AB  - PURPOSE: To determine the correlation between global ratings and criterion-based
      checklist scores, and inter-rater reliability of global ratings and criterion
      based checklist scores, in a performance assessment using an anesthesia
      simulator. METHOD: All final-year medical students at the University of Toronto
      were invited to work through a 15-minute faculty-facilitated scenario using an
      anesthesia simulator. Students' performances were videotaped and analyzed by two
      faculty using a 25-point criterion-based checklist and a five-point global rating
      of competency (1 = clear failure, 5 = superior performance). Correlations between
      global ratings and checklist scores, as well as specific performance competencies
      (knowledge, technical skills, and judgment), were determined. Checklist and
      global scores were converted to percentages; means of the two marks were
      compared. Mean reliability of a single rater for both checklist and global
      ratings was determined. RESULTS: The correlation between checklist and global
      ratings was.74. Mean ratings of both checklist and global scores were low (58.67,
      SD = 14.96, and 57.08, SD = 24.27, respectively); these differences were not
      statistically significant. For a single rater, the mean reliability score across
      rater pairs for checklist scores was.77 (range.58-.93). Mean reliability score
      across rater pairs for global ratings was.62 (.40-.77). Global ratings correlated
      more highly with technical skills and judgment (r =.51 and r =.53, respectively)
      than with knowledge. (r =.24) CONCLUSION: Inter-rater reliability was higher for
      checklist scores than for global ratings; however, global ratings demonstrated
      acceptable inter-rater reliability and may be useful for competency assessment in
      performance assessments using simulators.

PMID- 11597849
TI  - Evaluation of an early medical school selection program for underrepresented
      minority students.
AB  - PURPOSE: To evaluate the academic performance in the first two years of medical
      school of underrepresented minority students (URMS) who participated in an early
      identification and admission program. METHOD: The study involved 39 early
      selection URM students who entered one medical school from 1992 through 1999.
      Successful completion of the first two years of medical school and passing the
      United States Medical Licensure Examination (USMLE) Step 1 were correlated with
      Scholastic Aptitude Test I (SAT I) scores and Medical College Admission Test
      (MCAT) scores. The students were required to maintain an overall grade-point
      average of at least 3.0 on a 4.0 scale to remain in the program. RESULTS:
      Students who had combined scores of at least 900 on the SAT I and total scores of
      at least 18 on the three multiple-choice sections of the MCAT had more success
      completing the first two years of medical school and passed USMLE Step 1 with
      greater frequency than did those students who scored at lower levels on these
      tests. CONCLUSION: An early-selection program for URM students can identify early
      in their academic careers students who can complete the first two years of
      medical school and pass the USMLE Step 1.

PMID- 11597850
TI  - The incremental value of internet-based instruction as an adjunct to classroom
      instruction: a prospective randomized study.
AB  - PURPOSE: Computer-based methods of instruction offer the possibility of helping
      medical students to learn clinical skills and professionalism. Without rigorous
      documentation of its pedagogic advantages, the utility of Internet-based teaching
      is not solidly grounded. The authors carried out a prospective, randomized study
      of educational outcomes, comparing a traditional classroom course in clinical
      ethics with the same course supplemented by Internet-based discussion. METHODS:
      Introduction to Clinical Ethics is a sophomore medical school course that teaches
      a specific method for analyzing clinical ethical problems. One sophomore class
      was randomly assigned to either classroom teaching alone (traditional group; n =
      65) or classroom teaching supplemented with Internet-based discussions of cases
      illustrating ethical issues (Internet component group; n = 62). A final case
      analysis comprehensively evaluated students' understanding of the analytic method
      taught in the course. Grades for both groups on the final case analyses, which
      were rated by two external reviewers, were compared. RESULTS: The students'
      understanding of ethical analysis, as measured by grades of external reviewers on
      the final paper, was significantly higher for those in the course with the
      Internet component than it was for those in the traditional course (3.0 +/- 0.6
      and 2.6 +/- 0.7, respectively; p <.005). CONCLUSION: The study documents the
      incremental value of Internet-based teaching of clinical ethics to sophomore
      medical students.

PMID- 11597851
TI  - Can first-year students master clinical skills?
AB  - Performances on a clinical skills OSCE of first- and second-year students were
      compared to measure the success of a new interviewing and physical examination
      component of the first-year curriculum.

PMID- 11597852
TI  - A new course in age-based medicine at the University Medical Center of Nijmegen.
AB  - In 1995 the Medical Faculty of the University Medical Center of Nijmegen revised
      its curriculum to be more problem-oriented and student-centered. Each of the
      first four years now consists of ten four-week courses constructed around
      specific learning objectives. For the new curriculum the authors developed a
      fourth-year course on age-related health problems in which selected issues of
      pediatrics, general practice, and geriatrics are integrated. The primary
      objective of this course is to enable students to understand the differences and
      similarities in approaches to health problems in different age groups. Moreover,
      by the end of the course students should be able to analyze the physical,
      psychological, and social aspects of age-specific medical problems and understand
      their consequences for prevention and treatment. The course covers age-specific
      health concerns (e.g., neonatal jaundice, growth problems, sudden infant death
      syndrome, anorexia nervosa, dementia, multiple pathology, frailty) as well as
      important age-related differences in pathophysiology, etiology, diagnosis, and
      treatment (e.g., acute abdomen, constipation, maltreatment, urinary incontinence,
      pharmacokinetics). Based on assessments and evaluations after the first three
      implementations, the authors conclude that the enthusiastically received course
      is an effective introduction to age-specific health problems.

PMID- 11597853
TI  - An interdisciplinary course in the basic sciences for senior medical and PhD
      students.
AB  - Integrating clinical and basic sciences throughout the medical school curriculum
      has become a major objective of various innovations in medical education. While
      early clinical exposure has evolved as an efficient means of introducing clinical
      studies in the preclinical years, interdisciplinary integration of basic sciences
      during the clinical years remains a challenge. The authors describe their three
      years of experience with an interdisciplinary course designed to demonstrate the
      continuum of medical information from the clinic to the basic sciences. In this
      course, sixth-year medical students are required to choose one of three to four
      different one-week programs, each of which requires them to conduct an in-depth
      investigation of a defined clinical topic. Program coordinators are encouraged to
      work in clinician-basic scientist teams and to use a variety of teaching methods,
      with an emphasis on tutored individual and group learning based on critical
      readings of original papers. Coordinators are also encouraged to enable graduate
      research students to participate. From 1998 to 2000, students participated in
      nine programs, seven of which were coordinated by interdisciplinary teams.
      Several clinical and basic science disciplines were represented in each program,
      and various teaching methods were used. Graduate students participated in two of
      the programs. Evaluation of the programs (a debriefing discussion as well as
      short written evaluations) indicated moderate to good achievement of the course
      objectives.

PMID- 11597854
TI  - Integrating public health into medical education: community health projects in a
      Primary Care Preceptorship.
AB  - Physicians must integrate care of populations with the care of individual
      patients to function optimally in today's health care environment. With this
      understanding, medical school curricula are increasingly addressing the skills
      and knowledge of public health along with those of clinical medicine. The
      University of Utah School of Medicine in 1997 revised its four-year curriculum to
      increase the teaching of topics needed by future physicians, including public
      health. This report describes one course in the curriculum, the Primary Care
      Preceptorship (PCP), a fourth-year, six-week required rotation that assists
      students in learning about the health needs of a community along with providing
      primary care for its individual residents. Students in the PCP spend
      approximately 60% of their time in clinical primary care and 40% completing a
      community health project. In the first year of the PCP, 32 students completed
      projects on clinical problems, 27 on community health needs assessment, 26 on
      patient education, and 15 on epidemiology.

PMID- 11597855
TI  - Seven principles for teaching procedural and technical skills.
AB  - The authors developed a cognitive-theory-based checklist of seven important
      principles for teaching technical skills. They then used the checklist in a
      workshop for doctors who teach procedural and technical skills. Participants in
      the workshop found the principle-based approach to be more effective than the
      traditional "see one, do one, teach one" approach.

PMID- 11597856
TI  - Residents-as-teachers training in U.S. residency programs and offices of graduate
      medical education.

PMID- 11597857
TI  - Distinguishing sexual harassment from discrimination: a factor-analytic study of
      residents' reports.

PMID- 11597858
TI  - Students' perceptions of the effectiveness of interns' teaching during the
      internal medicine clerkship.

PMID- 11597859
TI  - Does "shortness of breath" = "dyspnea"? The biasing effect of feature
      instantiation in medical diagnosis.

PMID- 11597860
TI  - History-taking behaviors associated with diagnostic competence of clerks: an
      exploratory study.

PMID- 11597861
TI  - Effect of a diagnostic suggestion on diagnostic accuracy and identification of
      clinical features.

PMID- 11597862
TI  - The certification status of generalist physicians and the mortality of their
      patients after acute myocardial infarction.

PMID- 11597863
TI  - Comparing patient-management skills of referred physicians and non-referred
      physicians on a computer-based case-simulation examination.

PMID- 11597864
TI  - Resident and faculty adherence to common guidelines.

PMID- 11597865
TI  - The dean's letter summary statement: valuing scholarship, leadership, and
      academic achievement.

PMID- 11597866
TI  - A generalizability study of a standardized rating form used to evaluate
      instructional quality in clinical ambulatory sites.

PMID- 11597867
TI  - The fourth-year medical curriculum: has anything changed in 20 years?

PMID- 11597868
TI  - Explanations of basic medical information by students: what lay people find
      effective.

PMID- 11597869
TI  - Medical students' attitudes toward patient-centered care and standardized
      patients' perceptions of humanism: a link between attitudes and outcomes.

PMID- 11597870
TI  - The rhetoric of rationalization: how students grapple with professional dilemmas.

PMID- 11597871
TI  - Using basic science subject tests to identify students at risk for failing step
      1.

PMID- 11597872
TI  - The contribution of noncognitive characteristics in predicting MCAT scores.

PMID- 11597873
TI  - Estimating the pre-interview rankings of underrepresented minority applicants
      when ethnicity is not considered in the admission process.

PMID- 11597874
TI  - Change of interest in surgery during medical school: a comparison of men and
      women.

PMID- 11597875
TI  - Stresses and workplace resources for academic junior faculty: track and gender
      comparisons.

PMID- 11597876
TI  - Gender segregation by specialty during medical school.

PMID- 11597877
TI  - Longitudinal outcomes of an executive-model program for faculty development.

PMID- 11597878
TI  - Perceived self-efficacy for performing key physician-faculty functions--a
      baseline assessment of participants in a one-year faculty development program.

PMID- 11597879
TI  - Development of junior faculty's self-efficacy: outcomes of a National Center of
      Leadership in Academic Medicine.

PMID- 11597880
TI  - Patients' satisfaction with their family physicians' communication skills: a Nova
      Scotia survey.

PMID- 11597881
TI  - Developing competency-assessment tools to measure the family physician's ability
      to respond to the needs of the community.

PMID- 11597882
TI  - Cognitive benefits of problem-based learning: do they persist through clinical
      training?

PMID- 11597883
TI  - Difficulties in recognizing one's own incompetence: novice physicians who are
      unskilled and unaware of it.

PMID- 11597884
TI  - Using standardized patients to assess medical students' professionalism.

PMID- 11597885
TI  - Assessing sources of score variability in a multisite medical performance
      assessment: an application of hierarchial linear modeling.

PMID- 11597886
TI  - The interaction of examinee's ethnicity and standardized patient's ethnicity: an
      extended analysis.

PMID- 11597887
TI  - Appraisal of clinical competence during clerkships: how knowledgeable in
      curriculum and assessment development should a physician-examiner be?

PMID- 11597888
TI  - Quality assurance data for residents' global performance ratings.

PMID- 11597889
TI  - Global descriptive evaluations are more responsive than global numeric ratings in
      detecting students' progress during the inpatient portion of an internal medicine
      clerkship.

PMID- 11597890
TI  - Classification accuracy for tests that allow retakes.

PMID- 11597891
TI  - Developing an item pool for CBT: a practical comparison of three models of item
      writing.

PMID- 11597893
TI  - Ethics, revisited.

PMID- 11597892
TI  - Relationships among item characteristics, examine characteristics, and response
      times on USMLE Step 1.

PMID- 11597894
TI  - Transcriptional mechanisms of acute lung injury.
AB  - Acute lung injury occurs as a result of a cascade of cellular events initiated by
      either infectious or noninfectious inflammatory stimuli. An elevated level of
      proinflammatory mediators combined with a decreased expression of anti
      inflammatory molecules is a critical component of lung inflammation. Expression
      of proinflammatory genes is regulated by transcriptional mechanisms. Nuclear
      factor-kappa B (NF-kappa B) is one critical transcription factor required for
      maximal expression of many cytokines involved in the pathogenesis of acute lung
      injury. Activation and regulation of NF-kappa B are tightly controlled by a
      complicated signaling cascade. In acute lung injury caused by infection of
      bacteria, Toll-like receptors play a central role in initiating the innate immune
      system and activating NF-kappa B. Anti-inflammatory cytokines such as interleukin
      10 and interleukin-13 have been shown to suppress inflammatory processes through
      inhibiting NF-kappa B activation. NF-kappa B can interact with other
      transcription factors, and these interactions thereby lead to greater
      transcriptional selectivity. Modification of transcription is likely to be a
      logical therapeutic target for acute lung injury.

PMID- 11597895
TI  - sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and
      pulmonary hypertension.
AB  - Utilizing aortopulmonary vascular graft placement, we established a lamb model of
      pulmonary hypertension that mimics congenital heart disease with increased
      pulmonary blood flow. We previously demonstrated that endothelial nitric oxide
      synthase (eNOS) is increased in lambs at age 4 wk. However, these lambs display a
      selective impairment of endothelium-dependent pulmonary vasodilation that is
      suggestive of a derangement downstream of NO release. Thus our objective was to
      characterize potential alterations in the expression and activity of soluble
      guanylate cyclase (sGC) and phosphodiesterase type 5 (PDE5) induced by increased
      pulmonary blood flow and pulmonary hypertension. Late-gestational fetal lambs (n
      = 10) underwent in utero placement of an aortopulmonary vascular graft (shunt).
      Western blotting analysis on lung tissue from 4-wk-old shunted lambs and age
      matched controls showed that protein for both subunits of sGC was increased in
      shunted lamb lungs compared with age-matched controls. Similarly, cGMP levels
      were increased in shunted lamb lungs compared with age-matched controls. However,
      PDE5 expression and activity were also increased in shunted lambs. Thus although
      cGMP generation was increased, concomitant upregulation of PDE5 expression and
      activity may have (at least partially) limited and accounted for the impairment
      of endothelium-dependent pulmonary vasodilation in shunted lambs.

PMID- 11597896
TI  - ET-1 stimulates pulmonary arterial smooth muscle cell proliferation via induction
      of reactive oxygen species.
AB  - Recent studies implicate reactive oxygen species (ROS) such as superoxide anions
      and H(2)O(2) in the proliferation of systemic vascular smooth muscle cells
      (SMCs). However, the role of ROS in SMC proliferation within the pulmonary
      circulation remains unclear. We investigated the effects of endothelin-1 (ET-1),
      a potential SMC mitogen, on ROS production and proliferation of fetal pulmonary
      artery SMCs (FPASMCs). Exposure to ET-1 resulted in increases in superoxide
      production and viable FPASMCs after 72 h. These increases were prevented by
      pretreatment with PD-156707. Treatment with pertussis toxin blocked the effects
      of ET-1, whereas cholera toxin stimulated superoxide production and increased
      viable cell numbers even in the absence of ET-1. Wortmannin, LY-294002,
      diphenyleneiodonium (DPI), 4-(2-aminoethyl)benzenesulfonyl fluoride, and apocynin
      also prevented the ET-1-mediated increases in superoxide production and viable
      cell numbers. Exposure to H(2)O(2) or diethyldithiocarbamate increased viable
      cell number by 37% and 50%, respectively. Conversely, ascorbic acid and DPI
      decreased viable cell number, which appeared to be due to an increase in
      programmed cell death. Our data suggest that ET-1 exerts a mitogenic effect on
      FPASMCs via an increase in ROS production and that antioxidants can block this
      effect via induction of apoptosis. Antioxidant treatment may therefore represent
      a potential therapy for pulmonary vascular diseases.

PMID- 11597897
TI  - Keratinocyte growth factor reduces alveolar epithelial susceptibility to in vitro
      mechanical deformation.
AB  - Keratinocyte growth factor (KGF) is a potent mitogen that prevents lung
      epithelial injury in vivo. We hypothesized that KGF treatment reduces ventilator
      induced lung injury by increasing the alveolar epithelial tolerance to mechanical
      strain. We evaluated the effects of in vivo KGF treatment to rats on the response
      of alveolar type II (ATII) cells to in vitro controlled, uniform deformation. KGF
      (5 mg/kg) or saline (no-treatment control) was instilled intratracheally in rats,
      and ATII cells were isolated 48 h later. After 24 h in culture, both cell groups
      were exposed to 1 h of continuous cyclic strain (25% change in surface area);
      undeformed wells were included as controls. Cytotoxicity was evaluated
      quantitatively with fluorescent immunocytochemistry. There was >1% cell death in
      undeformed KGF-treated and control groups. KGF pretreatment significantly reduced
      deformation-related cell mortality to only 2.2 +/- 1.3% (SD) from 49 +/- 5.5% in
      control wells (P < 0.001). Effects of extracellular matrix, actin cytoskeleton,
      and phenotype of KGF-treated and control cells were examined. The large reduction
      in deformation-induced cell death demonstrates that KGF protects ATII cells by
      increasing their strain tolerance and supports KGF treatment as a potential
      preventative measure for ventilator-induced lung injury.

PMID- 11597898
TI  - Changes in proteoglycans and lung tissue mechanics during excessive mechanical
      ventilation in rats.
AB  - Excessive mechanical ventilation results in changes in lung tissue mechanics. We
      hypothesized that changes in tissue properties might be related to changes in the
      extracellular matrix component proteoglycans (PGs). The effect of different
      ventilation regimens on lung tissue mechanics and PGs was examined in an in vivo
      rat model. Animals were anesthetized, tracheostomized, and ventilated at a tidal
      volume of 8 (VT(8)), 20, or 30 (VT(30)) ml/kg, positive end-expiratory pressure
      of 0 (PEEP(0)) or 1.5 (PEEP(1.5)) cmH(2)O, and frequency of 1.5 Hz for 2 h. The
      constant-phase model was used to derive airway resistance, tissue elastance, and
      tissue damping. After physiological measurements, one lung was frozen for
      immunohistochemistry and the other was reserved for PG extraction and Western
      blotting. After 2 h of mechanical ventilation, tissue elastance and damping were
      significantly increased in rats ventilated at VT(30)PEEP(0) compared with control
      rats (ventilated at VT(8)PEEP(1.5)). Versican, basement membrane heparan sulfate
      PG, and biglycan were all increased in rat lungs ventilated at VT(30)PEEP(0)
      compared with control rats. At VT(30)PEEP(0), heparan sulfate PG and versican
      staining became prominent in the alveolar wall and airspace; biglycan was mostly
      localized in the airway wall. These data demonstrate that alterations in lung
      tissue mechanics with excessive mechanical ventilation are accompanied by changes
      in all classes of extracellular matrix PG.

PMID- 11597899
TI  - Dose-dependent lung remodeling in transgenic mice expressing transforming growth
      factor-alpha.
AB  - Transgenic mice overexpressing human transforming growth factor-alpha (TGF-alpha)
      develop emphysema and fibrosis during postnatal alveologenesis. To assess dose
      related pulmonary alterations, four distinct transgenic lines expressing
      different amounts of TGF-alpha in the distal lung under control of the surfactant
      protein C (SP-C) promoter were characterized. Mean lung homogenate TGF-alpha
      levels ranged from 388 +/- 40 pg/ml in the lowest expressing line to 1,247 +/- 33
      pg/ml in the highest expressing line. Histological assessment demonstrated
      progressive alveolar airspace size changes that were more severe in the higher
      expressing TGF-alpha lines. Pleural and parenchymal fibrosis were only detected
      in the highest expressing line (line 28), and increasing terminal airspace area
      was associated with increasing TGF-alpha expression. Hysteresis on pressure
      volume curves was significantly reduced in line 28 mice compared with other lines
      of mice. There were no differences in bronchoalveolar lavage fluid cell count or
      differential that would indicate any evidence of lung inflammation among all
      transgenic lines. Proliferating cells were increased in line 28 without
      alterations of numbers of type II cells. We conclude that TGF-alpha lung
      remodeling in transgenic mice is dose dependent and is independent of pulmonary
      inflammation.

PMID- 11597900
TI  - Apoptosis by pan-caspase inhibitors in lipopolysaccharide-activated macrophages.
AB  - Although apoptosis has been observed in macrophages during the course of
      infections, the mechanism of apoptosis in activated macrophages is not fully
      understood. This study shows that pan-caspase inhibitor benzyloxycarbonyl-Val-Ala
      Asp-fluoromethylketone (ZVAD) or t-butyloxycarbonyl-Asp-fluoromethylketone (Boc
      D) caused the death of lipopolysaccharide (LPS)-activated macrophages and RAW
      264.7 cells with apoptotic features. The apoptosis was also observed in
      lipoprotein-treated bacteria but not in CpG oligonucleotide- or flagellin-treated
      macrophages, indicating a difference of cellular responses downstream of
      different Toll-like receptors. Consistent with the induction of cell death by pan
      caspase inhibitors, no activation of known caspases was detected in LPS-ZVAD
      treated cells, suggesting an involvement of unknown proapoptotic caspases in the
      cell death. ZVAD inhibited the activation of extracellular signal-regulated
      kinase (ERK) and p38 but not of nuclear factor (NF)-kappa B induced by LPS,
      suggesting that the ZVAD-sensitive molecule lies upstream of the ERK and p38
      pathways but downstream of the divergent site of NF-kappa B and mitogen-activated
      protein kinases. Our results demonstrate that apoptosis of macrophages induced by
      LPS+ZVAD is independent from the known proapoptotic caspases and suggest that
      activity of an unidentified ZVAD-sensitive molecule(s) is involved in the
      survival of LPS-activated macrophages.

PMID- 11597901
TI  - Genes other than TLR4 are involved in the response to inhaled LPS.
AB  - For several decades, the mouse strains C3H/HeJ and C57BL/10ScNCr have been known
      to be hyporesponsive to endotoxin or lipopolysaccharide (LPS). Recently,
      mutations in Toll-like receptor (TLR) 4 have been shown to underlie this aberrant
      response to LPS. To further determine the relationship between TLR4 and
      responsiveness to LPS, we genotyped 18 strains of mice for TLR4 and evaluated the
      physiological and biological responses of these strains to inhaled LPS. Of the 18
      strains tested, 6 were wild type for TLR4 and 12 had mutations in TLR4. Of those
      strains with TLR4 mutations, nine had mutations in highly conserved residues.
      Among the strains wild type for TLR4, the inflammatory response in the airway
      induced by inhalation of LPS showed a phenotype ranging from very sensitive
      (DBA/2) to hyporesponsive (C57BL/6). A broad spectrum of airway hyperreactivity
      after inhalation of LPS was also observed among strains wild type for TLR4.
      Although the TLR4 mutant strains C3H/HeJ and C57BL/10ScNCr were phenotypically
      distinct from the other strains with mutations in the TLR4 gene, the other
      strains with mutations for TLR4 demonstrated a broad distribution in their
      physiological and biological responses to inhaled LPS. The results of our study
      indicate that although certain TLR4 mutations can be linked to a change in the
      LPS response phenotype, additional genes are clearly involved in determining the
      physiological and biological responses to inhaled LPS in mammals.

PMID- 11597902
TI  - Inhibition of voltage-gated K(+) currents by endothelin-1 in human pulmonary
      arterial myocytes.
AB  - Recent studies demonstrate that endothelin-1 (ET-1) constricts human pulmonary
      arteries (PA). In this study, we examined possible mechanisms by which ET-1 might
      constrict human PA. In smooth muscle cells freshly isolated from these arteries,
      whole cell patch-clamp techniques were used to examine voltage-gated K(+) (K(V))
      currents. K(V) currents were isolated by addition of 100 nM charybdotoxin and
      were identified by current characteristics and inhibition by 4-aminopyridine (10
      mM). ET-1 (10(-8) M) caused significant inhibition of K(V) current. Staurosporine
      (1 nM), a protein kinase C (PKC) inhibitor, abolished the effect of ET-1. Rings
      of human intrapulmonary arteries (0.8-2 mm OD) were suspended in tissue baths for
      isometric tension recording. ET-1-induced contraction was maximal at 10(-8) M,
      equal to that induced by K(V) channel inhibition with 4-aminopyridine, and
      attenuated by PKC inhibitors. These data suggest that ET-1 constricts human PA,
      possibly because of myocyte depolarization via PKC-dependent inhibition of K(V).
      Our results are consistent with data we reported previously in the rat,
      suggesting similar mechanisms may be operative in both species.

PMID- 11597903
TI  - Chlorzoxazone or 1-EBIO increases Na(+) absorption across cystic fibrosis airway
      epithelial cells.
AB  - Previous studies demonstrated that chlorzoxazone or 1-ethyl-2-benzimidazolinone
      (1-EBIO) enhances transepithelial Cl(-) secretion by increasing basolateral K(+)
      conductance (G(K)) (Singh AK, Devor DC, Gerlach AC, Gondor M, Pilewski JM, and
      Bridges RJ. J Pharmacol Exp Ther 292: 778-787, 2000). Hence these compounds may
      be useful to treat cystic fibrosis (CF) airway disease. The goal of the present
      study was to determine whether chlorzoxazone or 1-EBIO altered ion transport
      across Delta F508-CF transmembrane conductance regulator homozygous CFT1 airway
      cells. CFT1 monolayers exhibited a basal short-circuit current that was abolished
      by apical amiloride (inhibition constant 320 nM) as expected for Na(+)
      absorption. The addition of chlorzoxazone (400 microM) or 1-EBIO (2 mM) increased
      the amiloride-sensitive I(sc) approximately 2.5-fold. This overlapping
      specificity may preclude use of these compounds as CF therapeutics. Assaying for
      changes in the basolateral G(K) with a K(+) gradient plus the pore-forming
      antibiotic amphotericin B revealed that chlorzoxazone or 1-EBIO evoked an
      approximately 10-fold increase in clotrimazole-sensitive G(K). In contrast,
      chlorzoxazone did not alter epithelial Na(+) channel-mediated currents across
      basolateral-permeabilized monolayers or in Xenopus oocytes. These data further
      suggest that alterations in basolateral G(K) alone can modulate epithelial Na(+)
      transport.

PMID- 11597904
TI  - Autocrine signaling by IL-10 mediates altered responsiveness of atopic sensitized
      airway smooth muscle.
AB  - To elucidate the role and mechanism of action of interleukin (IL)-10 in
      regulating airway smooth muscle (ASM) responsiveness in the atopic asthmatic
      state, isolated rabbit tracheal ASM segments were passively sensitized with serum
      from atopic asthmatic patients or nonatopic nonasthmatic (control) subjects in
      both the absence and presence of an anti-IL-10 receptor blocking antibody (Ab).
      Relative to control ASM, atopic asthmatic serum-sensitized tissues exhibited
      enhanced isometric constrictor responses to administered acetylcholine and
      attenuated the relaxation responses to isoproterenol. These proasthmatic effects
      were prevented in atopic asthmatic serum-sensitized ASM that was pretreated with
      anti-IL-10 receptor Ab. In complementary experiments, exposure of cultured human
      ASM cells to atopic asthmatic serum induced upregulated expression of IL-10 mRNA.
      Moreover, extended studies demonstrated that 1) exogenous IL-10 administration to
      naive ASM elicited augmented contractility to acetylcholine and impaired
      relaxation to isoproterenol, 2) these effects of IL-10 were prevented by
      pretreating the tissues with an IL-5 receptor Ab, and 3) IL-10 administration
      induced upregulated mRNA expression and release of IL-5 protein from cultured ASM
      cells. Collectively, these findings provide new evidence demonstrating that the
      altered responsiveness of atopic asthmatic serum-sensitized ASM is largely
      attributed to activation of an intrinsic T helper type 2-type autocrine mechanism
      involving IL-10-mediated release and the action of IL-5 in the sensitized ASM
      itself.

PMID- 11597905
TI  - Upregulation of transcription factors in lung in the early phase of
      postpneumonectomy lung growth.
AB  - In the adult rodent, pneumonectomy results in compensatory lung growth
      characterized by cell proliferation. The molecular mechanisms governing this
      response remain unknown. We hypothesized that, in the early period
      postpneumonectomy, upregulated expression of transcription factors drives the
      growth process. We utilized a cDNA expression array to screen for upregulated
      transcription factors after left pneumonectomy in adult C57BL/6 mice, using
      unoperated mice as controls. Quantification of mRNA expression in the remaining
      lung at 2 h demonstrated a twofold or greater upregulation of six transcription
      factors: early growth response gene-1 (Egr-1), Nurr77, tristetraprolin, the
      primary inhibitor of nuclear factor-kappa B (I kappa B-alpha), gut-enriched
      Kruppel-like factor (GKLF), and LRG-21. Northern analysis was used to quantify
      the upregulation of expression of these genes relative to sham thoracotomy and
      unoperated controls. The largest increase was in Egr-1 (4.7-fold > naive). Time
      course analysis over the first 24 h confirmed the transient nature of the early
      upregulation. In the context that postpneumonectomy lung growth is associated
      with cell proliferation and that genes such as Egr-1, Nurr77, LRG-21, and
      tristetraprolin have known roles in stress response, vascular biology,
      embryology, and cellular development, these data support the concept that
      transcription factors function early in the cascade of events leading to the
      compensatory response.

PMID- 11597906
TI  - Hyperoxia increases leptin production: a mechanism mediated through endogenous
      elevation of corticosterone.
AB  - Leptin, a cytokine involved in the regulation of food intake, has been reported
      to be decreased in lung diseases such as chronic obstructive pulmonary disease
      and cystic fibrosis and increased in critically ill patients with sepsis. We
      investigated the role of leptin during hyperoxia in mice, which results in
      alveolar edema, severe weight loss, and death within 3-4 days. In oxygen
      breathing mice, serum leptin was increased six- to sevenfold and its mRNA was
      upregulated in white adipose tissue. Leptin elevation could not be attributed to
      changes in circulating tumor necrosis factor-alpha but was completely dependent
      on endogenous corticosterone elevation because adrenalectomized mice did not
      exhibit any increase in leptin levels. Using leptin-deficient mice and wild-type
      mice treated with anti-leptin antibody, we demonstrate that weight loss was
      leptin independent. Lung damage was moderately attenuated in leptin-deficient
      mice but was not modified by anti-leptin antibody or leptin administration,
      suggesting that leptin does not play an essential role in the direct and short
      term effects of oxygen-induced injury.

PMID- 11597907
TI  - NO and prostaglandin interactions during hemodynamic stress in the fetal ovine
      pulmonary circulation.
AB  - Nitric oxide (NO) and prostacyclin (PGI(2)) are potent fetal pulmonary
      vasodilators, but their relative roles and interactions in the regulation of the
      perinatal pulmonary circulation are poorly understood. We compared the separate
      and combined effects of nitric oxide synthase (NOS) and cyclooxygenase (COX)
      inhibition during acute hemodynamic stress caused by brief mechanical compression
      of the ductus arteriosus (DA) in chronically prepared fetal lambs. Nitro-L
      arginine (L-NNA; NOS antagonist), meclofenamate (Mec; COX inhibitor), combined
      drugs (L-NNA-Mec), or saline (control) was infused into the left pulmonary artery
      (LPA) before DA compression. In controls, DA compression decreased pulmonary
      vascular resistance (PVR) by 43% (P < 0.01). L-NNA, but not Mec, treatment
      completely blocked vasodilation and caused a paradoxical increase in PVR (+31%; P
      < 0.05). The effects of L-NNA-Mec and L-NNA on PVR were similar. To determine if
      the vasodilator effect of PGI(2) is partly mediated by NO release, we studied
      PGI(2)-induced vasodilation before and after NOS inhibition. L-NNA treatment
      blocked the PGI(2)-induced rise in LPA blood flow by 73% (P < 0.001). We conclude
      that NO has a greater role than PGs in fetal pulmonary vasoregulation during
      acute hemodynamic stress and that PGI(2)-induced pulmonary vasodilation is
      largely mediated by NO release in the fetal lung.

PMID- 11597908
TI  - Partial correction of defective Cl(-) secretion in cystic fibrosis epithelial
      cells by an analog of squalamine.
AB  - Defective cystic fibrosis (CF) transmembrane conductance regulator (CFTR)
      mediated Cl(-) transport across the apical membrane of airway epithelial cells is
      implicated in the pathophysiology of CF lungs. A strategy to compensate for this
      loss is to augment Cl(-) transport through alternative pathways. We report here
      that partial correction of this defect could be attained through the
      incorporation of artificial anion channels into the CF cells. Introduction of GL
      172, a synthetic analog of squalamine, into CFT1 cells increased cell membrane
      halide permeability. Furthermore, when a Cl(-) gradient was generated across
      polarized monolayers of primary human airway or Fischer rat thyroid cells in an
      Ussing chamber, addition of GL-172 caused an increase in the equivalent short
      circuit current. The magnitude of this change in short-circuit current was ~30%
      of that attained when CFTR was maximally stimulated with cAMP agonists. Patch
      clamp studies showed that addition of GL-172 to CFT1 cells also increased whole
      cell Cl(-) currents. These currents displayed a linear current-voltage
      relationship and no time dependence. Additionally, administration of GL-172 to
      the nasal epithelium of transgenic CF mice induced a hyperpolarization response
      to perfusion with a low-Cl(-) solution, indicating restoration of Cl(-)
      secretion. Together, these results demonstrate that in CF airway epithelial
      cells, administration of GL-172 is capable of partially correcting the defective
      Cl(-) secretion.

PMID- 11597909
TI  - Examining basal chloride transport using the nasal potential difference response
      in a murine model.
AB  - Epithelia of humans and mice with cystic fibrosis are unable to secrete chloride
      in response to a chloride gradient or to cAMP-elevating agents. Bioelectrical
      properties measured using the nasal transepithelial potential difference (TEPD)
      assay are believed to reflect these cystic fibrosis transmembrane conductance
      regulator (CFTR)-dependent chloride transport defects. Although the response to
      forskolin is CFTR mediated, the mechanisms responsible for the response to a
      chloride gradient are unknown. TEPD measurements performed on inbred mice were
      used to compare the responses to low chloride and forskolin in vivo. Both
      responses show little correlation between or within inbred strains of mice,
      suggesting they are mediated through partially distinct mechanisms. In addition,
      these responses were assayed in the presence of several chloride channel
      inhibitors, including DIDS, diphenylamine-2-carboxylate, glibenclamide, and 5
      nitro-2-(3-phenylpropylamino)-benzoic acid, and a protein kinase A inhibitor, the
      Rp diastereomer of adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS). The
      responses to low chloride and forskolin demonstrate significantly different
      pharmacological profiles to both DIDS and Rp-cAMPS, indicating that channels in
      addition to CFTR contribute to the low chloride response.

PMID- 11597910
TI  - Induction of c-jun and TGF-beta 1 in Fischer 344 rats during amiodarone-induced
      pulmonary fibrosis.
AB  - Amiodarone (AM) is an antidysrhythmic agent with a propensity to cause pulmonary
      toxicity, including potentially fatal fibrosis. In the present study, the
      potential roles of c-Jun and transforming growth factor (TGF)-beta 1 in AM
      induced inflammation and fibrogenesis were examined after intratracheal
      administration of AM (1.83 micromol/day on days 0 and 2) or an equivalent volume
      (0.4 ml) of distilled water to male Fischer 344 rats. Northern and immunoblot
      analyses demonstrated that lung TGF-beta 1 (mRNA and protein) expression was
      increased 1.5- to 1.8-fold relative to control during the early inflammation
      period and 1 day, 1 wk, and 2 wk post-AM treatment. Lung c-Jun protein expression
      was increased concomitantly with evidence of AM-induced fibrosis; at 5 wk post-AM
      treatment, c-Jun protein was increased 3.3-fold relative to control. The results
      indicate a role for induction of c-jun and TGF-beta 1 expression in the
      development of AM-induced pulmonary fibrosis in the Fischer 344 rat and provide
      potential targets for therapeutic intervention.

PMID- 11597911
TI  - Amiodarone inhibits lung degradation of SP-A and perturbs the distribution of
      lysosomal enzymes.
AB  - Amiodarone may induce lung damage by direct toxicity or indirectly through
      inflammation. To clarify the mechanism of direct toxicity, we briefly exposed
      rabbit alveolar macrophages to amiodarone and analyzed their morphology,
      synthesis, and degradation of dipalmitoylphosphatidylcholine (DPPC); distribution
      of lysosomal enzymes; and uptake of diphtheria toxin and surfactant protein (SP)
      A used as tracers of the endocytic pathway. Furthermore, in newborn rabbits, we
      studied the clearance of DPPC and SP-A instilled into the trachea together with
      increasing amounts of amiodarone. We found that in vitro amiodarone decreases the
      surface density of mitochondria and lysosomes while increasing the surface
      density of inclusion bodies, increases the incorporation of choline into DPPC,
      modifies the distribution of lysosomal enzymes, and does not affect the uptake
      and processing of diphtheria toxin but inhibits the degradation of SP-A. In vivo
      amiodarone inhibits the degradation of SP-A but not of DPPC. We conclude that the
      acute exposure to amiodarone perturbs the endocytic pathway acting after the
      early endosomes, alters the traffic of lysosomal enzymes, and interferes with the
      turnover of SP-A.

PMID- 11597912
TI  - Genetic variability in the development of pulmonary tolerance to inhaled
      pollutants in inbred mice.
AB  - After repeated exposures, many individuals develop tolerance to the adverse
      health effects of inhaled pollutants. Pulmonary tolerance can be characterized as
      the ability of the lung to withstand the adverse actions of a toxic compound
      after repeated exposures. To determine whether genetic background is important to
      the development of pulmonary tolerance to inhaled pollutants, 11 inbred strains
      of mice were exposed once (1x) or for 5 consecutive days (5x) to 1.0 mg/m(3) of
      zinc oxide (ZnO). Development of pulmonary tolerance was assessed by measuring
      polymorphonuclear leukocyte and protein levels in bronchoalveolar lavage fluid
      and comparing the responses of the 1x and 5x groups. Significant interstrain
      variation in polymorphonuclear leukocyte and protein responses was observed
      between the groups with 1x and 5x exposures, which indicates that genetic
      background has an important role in the development of pulmonary tolerance. The
      BALB/cByJ strain and the DBA/2J strain were the most tolerant and nontolerant,
      respectively. The CByD2F1/J offspring were uniformly nontolerant. The development
      of tolerance was also investigated in BALB/cByJ and DBA/2J mice after 1x and 5x
      exposure to ozone and aerosolized endotoxin. Discordance in the phenotypic
      pattern of pulmonary tolerance among strains after exposure to ZnO, ozone, and
      endotoxin suggested that different mechanisms may be responsible for the
      development of pulmonary tolerance to these agents.

PMID- 11597913
TI  - Impaired functional activity of alveolar macrophages from GM-CSF-deficient mice.
AB  - We hypothesized that pulmonary granulocyte-macrophage colony-stimulating factor
      (GM-CSF) is critically involved in determining the functional capabilities of
      alveolar macrophages (AM) for host defense. To test this hypothesis, cells were
      collected by lung lavage from GM-CSF mutant mice [GM(-/-)] and C57BL/6 wild-type
      mice. GM(-/-) mice yielded almost 4-fold more AM than wild-type mice. The
      percentage of cells positive for the beta(2)-integrins CD11a and CD11c was
      reduced significantly in GM(-/-) AM compared with wild-type cells, whereas
      expression of CD11b was similar in the two groups. The phagocytic activity of GM(
      /-) AM for FITC-labeled microspheres was impaired significantly compared with
      that of wild-type AM both in vitro and in vivo (after intratracheal inoculation
      with FITC-labeled beads). Stimulated secretion of tumor necrosis factor-alpha
      (TNF-alpha) and leukotrienes by AM from the GM(-/-) mice was greatly reduced
      compared with wild-type AM, whereas secretion of monocyte chemoattractant protein
      1 was increased. Transgenic expression of GM-CSF exclusively in the lungs of GM(
      /-) mice resulted in AM with normal or supranormal expression of CD11a and CD11c,
      phagocytic activity, and TNF-alpha secretion. Thus, in the absence of GM-CSF, AM
      functional capabilities for host defense were significantly impaired but were
      restored by lung-specific expression of GM-CSF.

PMID- 11597914
TI  - Translational activation and repression by distinct elements within the 5'-UTR of
      ENaC alpha-subunit mRNA.
AB  - The rat amiloride-sensitive epithelial Na(+) channel (rENaC), the rate-limiting
      step in epithelial Na(+) transport, consists of three subunits, alpha, beta, and
      gamma. We hypothesized that alpha-rENaC translation is regulated via its 5'
      untranslated region (UTR). Transient transfections of alpha-rENaC promoter
      reporter constructs in representative epithelial cell lines demonstrated up to
      fivefold differences in activity among constructs containing different amounts of
      the alpha-rENaC 5'-UTR sequence. Differences in reporter protein activity did not
      parallel differences in reporter mRNA, demonstrating that 5'-UTR regulation must
      be at the level of translation. Specifically, translation was enhanced by a
      region extending from +53 to +211 bp downstream from the transcription start site
      and repressed by the region between +367 and +499 bp. Examination of the 5'-UTR
      sequence revealed an out-of-frame initiation codon within the repressive region,
      43 bp upstream from the start of the alpha-rENaC open reading frame. Mutational
      analysis of this upstream start codon indicated that it plays, at most, a minor
      role in impeding translation both in vitro and in vivo, suggesting that
      additional mechanisms of translational regulation are operative.

PMID- 11597915
TI  - Cytokine treatment increases arginine metabolism and uptake in bovine pulmonary
      arterial endothelial cells.
AB  - L-Arginine (L-Arg) is metabolized to nitric oxide (NO) by NO synthase (NOS) or to
      urea by arginase (AR). L-Arg is transported into bovine pulmonary arterial
      endothelial cells (BPAECs) by cationic amino acid transporter-2 (CAT-2). We
      hypothesized that cytokine treatment would increase L-Arg metabolism and increase
      CAT-2 mRNA expression. BPAECs were incubated for 24 h in medium (control) or
      medium with lipopolysaccharide and tumor necrosis factor-alpha (L-T). L-T
      increased nitrite production (3.1 +/- 0.4 nmol/24 h vs. 1.8 +/- 0.1 nmol/24 h for
      control; P < 0.01) and urea production (83.5 +/- 29.5 nmol/24 h vs. 17.8 +/- 8.6
      nmol/24 h for control; P < 0.05). L-T-treated BPAECs had greater endothelial and
      inducible NOS mRNA expression compared with control cells. Increasing the medium
      L-Arg concentration resulted in increased nitrite and urea production in both the
      control and the L-T-treated BPAECs. L-T treatment resulted in measurable CAT-2
      mRNA. L-T increased L-[(3)H]Arg uptake (5.78 +/- 0.41 pmol vs. 4.45 +/- 0.10 pmol
      for control; P < 0.05). In summary, L-T treatment increased L-Arg metabolism to
      both NO and urea in BPAECs and resulted in increased levels of CAT-2 mRNA. This
      suggests that induction of NOS and/or AR is linked to induction of CAT-2 in
      BPAECs and may represent a mechanism for maintaining L-Arg availability to NOS
      and/or AR.

PMID- 11597916
TI  - Direct and indirect bacterial killing functions of neutrophil defensins in lung
      explants.
AB  - Studies of the antimicrobial activity of neutrophil defensins have mostly been
      carried out in microbiological media, and their effects on the host defense in
      physiological conditions are unclear. We examined 1) the antibacterial activity
      of defensins in physiological media with and without lung tissue present, 2) the
      effect of defensins on hydrogen peroxide (H(2)O(2)) production by lung tissue
      that had been exposed to bacteria, and 3) the effect of diphenyleneiodonium
      (DPI), an inhibitor of reactive oxygen species formation, on the antibacterial
      activity of defensins in the presence of lung tissue. Defensins were incubated
      with Escherichia coli or Pseudomonas aeruginosa in the absence or presence of
      primary cultured mouse lung explants. Defensins reduced bacterial counts by
      approximately 65-fold and approximately 25-fold, respectively, at 48 h; bacterial
      counts were further decreased by approximately 600-fold and approximately 12,000
      fold, respectively, in the presence of lung tissue. Defensins induced H(2)O(2)
      production by lung tissue, and the rate of killing of E. coli by defensins was
      reduced by approximately 2,500-fold in the presence of 10 microM DPI. We conclude
      that defensins exert a significant antimicrobial effect under physiological
      conditions and that this effect is enhanced in the presence of lung tissue by a
      mechanism that involves the production of reactive oxygen species.

PMID- 11597917
TI  - Lung fibroblasts inhibit activation-induced death of T cells through PGE(2)
      dependent mechanisms.
AB  - Activation-induced cell death (AICD) is a regulatory mechanism eliminating excess
      activated T cells, mainly through a Fas/Fas ligand-dependent mechanism. The goal
      of this study was to determine whether mouse primary lung fibroblasts are capable
      of modulating AICD. Using T cell hybridoma DO11.10, we found that fibroblasts in
      coculture rescue T cells from AICD. Fibroblast-conditioned medium (FCM) also
      inhibited apoptosis of T cells activated with immobilized anti-CD3 antibody. The
      effects of lung fibroblasts are mediated, in part, by secreted prostaglandin E(2)
      (PGE(2)) because treatment of fibroblasts with indomethacin decreased
      antiapoptotic activity of FCM. Addition of exogenous PGE(2) to FCM from
      fibroblast cultures treated with indomethacin restored the inhibitory activity of
      FCM. Expression of Fas receptor and Fas ligand by anti-CD3-activated DO11.10
      cells was not affected by PGE(2). However, the same concentrations of PGE(2)
      significantly downregulated activation of caspase-8 and caspase-3. These results
      demonstrate that lung fibroblasts inhibit the AICD of T cells by secreting
      PGE(2), which downregulates caspase activation and apoptosis.

PMID- 11597918
TI  - Prostaglandin E(2) inhibits fibroblast chemotaxis.
AB  - Fibroblasts are the major source of extracellular connective tissue matrix, and
      the recruitment, accumulation, and stimulation of these cells are thought to play
      important roles in both normal healing and the development of fibrosis.
      Prostaglandin E(2) (PGE(2)) can inhibit this process by blocking fibroblast
      proliferation and collagen production. The aim of this study was to investigate
      the inhibitory effect of PGE(2) on human plasma fibronectin (hFN)- and bovine
      bronchial epithelial cell-conditioned medium (BBEC-CM)-induced chemotaxis of
      human fetal lung fibroblasts (HFL1). Using the Boyden blind well chamber
      technique, PGE(2) (10(-7) M) inhibited chemotaxis to hFN 40.8 +/- 5.3% (P < 0.05)
      and to BBEC-CM 49.7 +/- 11.7% (P < 0.05). Checkerboard analysis demonstrated
      inhibition of both chemotaxis and chemokinesis. The effect of PGE(2) was
      concentration dependent, and the inhibitory effect diminished with time. Other
      agents that increased fibroblast cAMP levels, including isoproterenol (10(-5) M),
      dibutyryl cAMP (10(-5) M), and forskolin (3 x 10(-5) M) had similar effects and
      inhibited chemotaxis 54.1, 95.3, and 87.0%, respectively. The inhibitory effect
      of PGE(2) on HFL1 cell chemotaxis was inhibited by the cAMP-dependent protein
      kinase (PKA) inhibitor KT-5720, which suggests a cAMP-dependent effect mediated
      by PKA. In summary, PGE(2) appears to inhibit fibroblast chemotaxis, perhaps by
      modulating the rate of fibroblast migration. Such an effect may contribute to
      regulation of the wound healing response after injury.

PMID- 11597919
TI  - Decreased surfactant proteins in lambs with pulmonary hypertension secondary to
      increased blood flow.
AB  - Infants with increased pulmonary blood flow secondary to congenital heart disease
      suffer from tachypnea, dyspnea, and recurrent pulmonary infections. We have
      recently established a model of pulmonary hypertension secondary to increased
      pulmonary blood flow in lambs after in utero placement of an aortopulmonary
      vascular graft. The purpose of the present study was to utilize our animal model
      to determine the effects on the expression of surfactant proteins A (SP-A), B (SP
      B), and C (SP-C). At age 4 wk, SP-A mRNA content in lambs decreased to 61.4 +/-
      8% of age-matched control value (n = 5; P < 0.05). In addition, SP-A protein
      content was decreased to 50 +/- 12% of control value (n = 6; P < 0.0001).
      Although we did not observe statistically significant changes in SP-B mRNA
      content, SP-B protein was decreased to 74 +/- 25% of control value (n = 4; P <
      0.02). There was no difference in SP-C mRNA. These data show that in a model of
      congenital heart disease with pulmonary hypertension secondary to increased
      pulmonary blood flow, there is a decrease in SP-A gene expression as well as a
      decrease in SP-A and SP-B protein contents.

PMID- 11597920
TI  - Nuclear factor-kappa B augments beta(2)-adrenergic receptor expression in human
      airway epithelial cells.
AB  - Interleukin (IL)-1 beta increases beta(2)-adrenergic receptor (beta(2)-AR) mRNA
      and density by protein kinase C (PKC)-dependent mechanisms in human airway
      epithelial cells. The present study examined the role of several nuclear
      transcription factors in the PKC-activated upregulation of beta(2)-AR expression.
      BEAS-2B cells were exposed to the PKC activator phorbol 12-myristate 13-acetate
      (PMA; 0.1 microM for 2-18 h). PMA had no effect on activator protein (AP)-2 or
      cAMP response element binding protein DNA binding activity but markedly increased
      nuclear factor (NF)-kappa B and AP-1 binding as assessed by electrophoretic gel
      mobility shift assay. PMA also increased the activity of a beta(2)-AR promoter
      luciferase reporter construct in transiently transfected cells. These effects
      were inhibited by the PKC inhibitors Ro-31-8220 and calphostin C. Furthermore,
      with increasing Ro-31-8220, beta(2)-AR promoter-reporter activity correlated
      closely with both NF-kappa B and AP-1 activities (r > 0.89 for both). Finally,
      the selective NF-kappa B inhibitor MG-132 dose dependently reduced NF-kappa B
      binding and beta(2)-AR promoter activity but increased AP-1 binding. We conclude
      that PKC-induced upregulation of beta(2)-AR expression in human airway epithelial
      cells appears to be mediated, at least in part, by increases in NF-kappa B
      activity.

PMID- 11597921
TI  - Preventing mediastinal shift after pneumonectomy impairs regenerative alveolar
      tissue growth.
AB  - To examine the effects of mechanical lung strain on regenerative growth of
      alveolar septal tissue after pneumonectomy (PNX), we replaced the right lungs of
      adult dogs with a custom-shaped inflatable silicone prosthesis. The prosthesis
      was either inflated (Inf) to maintain the mediastinum at the midline or deflated
      to allow mediastinal shift. The animals were euthanized approximately 15 mo
      later, and the lungs were fixed at a constant distending pressure. With the Inf
      prostheses, lung expansion, alveolar septal tissue volumes, surface areas, and
      diffusing capacity of the tissue-plasma barrier were significantly lower than
      with the deflated prostheses; the expected post-PNX tissue responses were
      impaired by 30-60%. Capillary blood volume was significantly higher with Inf
      prostheses, consistent with microvascular congestion. Measurements in the Inf
      group remained consistently and significantly higher than those expected for a
      normal left lung, indicating persistence of partial compensation. In one dog,
      delayed deflation of the prosthesis 9-10 mo after PNX led to vigorous lung
      expansion and septal tissue growth, particularly of type II epithelial cells. We
      conclude that mechanical lung strain is a major signal for regenerative lung
      growth; however, other signals are also implicated, accounting for a significant
      fraction of the compensatory response to PNX.

PMID- 11597922
TI  - IL-4 differentially regulates eotaxin and MCP-4 in lung epithelium and
      circulating mononuclear cells.
AB  - To investigate the mechanisms of eosinophil recruitment in allergic airway
      inflammation, we examined the effects of interleukin (IL)-4, a Th2-type cytokine,
      on eotaxin and monocyte chemoattractant protein-4 (MCP-4) expression in human
      peripheral blood mononuclear cells (PBMCs; n = 10), in human lower airway
      mononuclear cells (n = 5), in the human lung epithelial cell lines A549 and BEAS
      2B, and in human cultured airway epithelial cells. IL-4 inhibited eotaxin and MCP
      4 mRNA expression induced by IL-1 beta and tumor necrosis factor-alpha in PBMCs
      but did not significantly inhibit expression in epithelial cells. Eotaxin and MCP
      4 mRNA expression was not significantly induced by proinflammatory cytokines in
      lower airway mononuclear cells. IL-1 beta-induced eotaxin and MCP-4 protein
      production was also inhibited by IL-4 in PBMCs, whereas IL-4 enhanced eotaxin
      protein production in A549 cells. In contrast, dexamethasone inhibited eotaxin
      and MCP-4 expression in both PBMCs and epithelial cells. The divergent effects of
      IL-4 on eotaxin and MCP-4 expression between PBMCs and epithelial cells may
      create chemokine concentration gradients between the subepithelial layer and the
      capillary spaces that may promote the recruitment of eosinophils to the airway in
      Th2-type responses.

PMID- 11597923
TI  - CCSP modulates airway dysfunction and host responses in an Ova-challenged mouse
      model.
AB  - Clara cell secretory protein (CCSP) is synthesized by nonciliated bronchiolar
      cells in the lung and modulates lung inflammation to infection. To determine the
      role of CCSP in the host response to allergic airway disease, CCSP-deficient [(-/
      )] mice were immunized twice with ovalbumin (Ova) and challenged by Ova (2 or 5
      mg/m(3)) aerosol. After 2, 3, and 5 days of Ova aerosol challenge (6 h/day),
      airway reactivity was increased in CCSP(-/-) mice compared with wild-type
      [CCSP(+/+)] mice. Neutrophils were markedly increased in the bronchoalveolar
      lavage fluid of CCSP(-/-) Ova mice, coinciding with increased myeloperoxidase
      activity and macrophage inflammatory protein-2 levels. Lung histopathology and
      inflammation were increased in CCSP(-/-) compared with wild-type mice after Ova
      challenge. Mucus production, as assessed by histological staining, was increased
      in the airway epithelium of CCSP(-/-) Ova mice compared with that in CCSP(+/+)
      Ova mice. These data suggest a role for CCSP in airway reactivity and the host
      response to allergic airway inflammation and provide further evidence for the
      role of the airway epithelium in regulating airway responses in allergic disease.

PMID- 11597924
TI  - Another calcium paradox?

PMID- 11597925
TI  - Evaluating atherosclerotic lesions by magnetic resonance imaging: from
      dimensional to compositional quantitation.

PMID- 11597926
TI  - Boning up (or down) on statins.

PMID- 11597927
TI  - Lipoprotein size and atherosclerosis susceptibility in Apoe(-/-) and Ldlr(-/-)
      mice.
AB  - Two hypercholesterolemic mouse models, the apo-E-deficient mouse (Apoe(-/-)) and
      the LDL receptor-deficient mouse (Ldlr(-/-)), have been used extensively as
      animal models of atherogenesis. Total plasma cholesterol levels in chow-fed Apoe(
      /-) mice are much higher than in Ldlr(-/-) mice. In a recent study, we managed to
      even-up the cholesterol levels in Apoe(-/-) mice and Ldlr(-/-) mice by making
      both models homozygous for the Apob(100) (apo B-100-only) allele. On a chow diet,
      apo-E-deficient apo B-100-only mice (Apoe(-/-)Apob(100/100)) and LDL receptor
      deficient apo B-100-only mice (Ldlr(-/-)Apob(100/100)) had similar total plasma
      cholesterol levels ( approximately 300 mg/dL). The plasma of Ldlr(-/
      )Apob(100/100) mice contained large numbers of small lipoproteins, whereas the
      plasma of Apoe(-/-)Apob(100/100) mice contained much lower levels of much larger
      lipoproteins. Interestingly, the Ldlr(-/-)Apob(100/100) mice developed far more
      extensive atherosclerotic lesions than the Apoe(-/-)Apob(100/100) mice. The
      finding of substantially more atherosclerosis in Ldlr(-/-)Apob(100/100) mice than
      in Apoe(-/-)Apob(100/100) mice, despite nearly identical cholesterol levels,
      suggests that large numbers of small apo B-100-containing lipoproteins are far
      more atherogenic than lower numbers of large apo B-100-containing lipoproteins.

PMID- 11597928
TI  - Induction of endothelial NO synthase by hydrogen peroxide via a Ca(2+)/calmodulin
      dependent protein kinase II/janus kinase 2-dependent pathway.
AB  - We have recently demonstrated that hydrogen peroxide (H(2)O(2)) is an extremely
      potent stimulus of endothelial NO synthase (eNOS) gene expression. The present
      study was designed to identify the signaling mechanisms mediating this response.
      Induction of eNOS expression by H(2)O(2) was found to be Ca(2+) dependent,
      inasmuch as it was blocked by BAPTA-AM. Further studies have indicated that
      Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) plays a critical
      role in mediating this response. Immunocytochemical staining with an anti-CaM
      kinase II antibody confirmed the expression of CaM kinase II in cultured bovine
      aortic endothelial cells. H(2)O(2) induced autophosphorylation of CaM kinase II
      and increased the activity of the enzyme, as assessed by an in-gel kinase assay.
      A specific inhibitor for CaM kinase II, KN93, and a calmodulin antagonist, W-7,
      attenuated eNOS induction by H(2)O(2). Further studies have indicated that janus
      kinase 2 is important in mediating increased eNOS expression in response to
      H(2)O(2) and likely is downstream from CaM kinase II. In conclusion, these data
      provide the first evidence that CaM kinase II plays a critical role in
      endothelial redox signaling. Regulation of eNOS via this pathway may represent an
      important vascular adaptation to oxidant stress.

PMID- 11597929
TI  - S17834, a new inhibitor of cell adhesion and atherosclerosis that targets nadph
      oxidase.
AB  - microdant stress is involved in the events that accompany endothelial cell
      expression of adhesion molecules and leukocyte adherence in many disease states,
      including atherosclerosis. A recently discovered benzo(b)pyran-4-one derivative,
      S17834 (10 to 50 micromol/L), reduced tumor necrosis factor-stimulated vascular
      cell adhesion molecule-1 (VCAM) mRNA accumulation and protein expression in human
      umbilical vein endothelial cells. Intercellular cell adhesion molecule-1 and E
      selectin were also inhibited by S17834, but platelet endothelial cell adhesion
      molecule-1 was not. Adherence of U937 monocytic cells to the endothelial cells as
      well as to plastic plates coated with soluble VCAM, intercellular cell adhesion
      molecule-1, P-selectin, and E-selectin was also decreased. Consistent with an
      antioxidant mechanism of action, S17834 (10 to 50 micromol/L) inhibited tumor
      necrosis factor-stimulated release of superoxide from endothelial cells measured
      by cytochrome c reduction. S17834 had no effect on superoxide produced by
      xanthine oxidase, indicating that rather than by acting as a scavenger of
      superoxide anion, the drug acts by inhibiting the production of free radicals.
      Indeed, S17834 inhibited NADPH oxidase activity of endothelial cell membranes.
      The ability to inhibit superoxide anion production appears to be key in the
      effect of S17834 on superoxide anion production and VCAM expression, because
      these actions were mimicked by adenovirus-mediated overexpression of superoxide
      dismutase. Furthermore, these actions may be relevant in vivo, because S17834
      reduced aortic superoxide anion levels by 40% and aortic atherosclerotic lesions
      by 60% in apolipoprotein E-deficient mice. These results indicate that S17834
      inhibits adhesion molecule expression and adherence of leukocytes to endothelial
      cells as well as aortic atherogenesis and that perhaps these effects can be
      explained by its ability to inhibit endogenous superoxide anion production.

PMID- 11597930
TI  - Increased transcription of IL-8 in endothelial cells is differentially regulated
      by TNF-alpha and oxidized phospholipids.
AB  - Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (Ox-PAPC)
      upregulates a spectrum of inflammatory cytokines and adhesion molecules different
      from those induced by classic inflammatory mediators such as tumor necrosis
      factor-alpha (TNF-alpha) or lipopolysaccharide. Interestingly, Ox-PAPC also
      induces the expression of a set of proteins similar to those induced by TNF-alpha
      or lipopolysaccharide, which include the chemokines monocyte chemotactic protein
      1 (MCP-1) and interleukin (IL)-8. To elucidate the molecular mechanisms of Ox
      PAPC-induced gene expression and to determine whether Ox-PAPC and other
      inflammatory mediators such as TNF-alpha utilize common signaling pathways, we
      examined the transcriptional regulation of IL-8 by Ox-PAPC and TNF-alpha in human
      aortic endothelial cells. Both Ox-PAPC and TNF-alpha induced the expression of IL
      8 mRNA in a dose-dependent fashion; however, the kinetics of IL-8 mRNA
      accumulation between the 2 ligands differed. Ox-PAPC-induced IL-8 mRNA was seen
      as early as 30 minutes, peaked between 4 and 8 hours, and decreased substantially
      by 24 hours. In contrast, TNF-alpha-induced IL-8 mRNA synthesis was elevated at
      30 minutes, peaked at 2 hours, and reached basal/undetectable levels by 6 hours.
      Actinomycin D experiments suggested that both Ox-PAPC and TNF-alpha regulate the
      expression of IL-8 at the transcriptional level. Furthermore, the half-life of IL
      8 mRNA for both ligands was similar (<30 minutes), suggesting that mRNA stability
      was not responsible for the differences in the kinetics of IL-8 accumulation
      between the 2 ligands. Transient transfection studies with reporter constructs
      containing 1.48 kb of the IL-8 promoter identified an Ox-PAPC-specific response
      region between -133 and -1481 bp of the IL-8 promoter. In contrast, TNF-alpha
      activation of the IL-8 promoter was mediated almost entirely through the nuclear
      factor-kappaB and activation protein-1 response elements present between -70 and 
      133 bp of the IL-8 promoter. Thus, although Ox-PAPC and TNF-alpha both induced IL
      8 synthesis, our data suggest that the 2 ligands utilize different mechanisms in
      the regulation of IL-8 transcription.

PMID- 11597931
TI  - Phosphatidylinositol 3-OH kinase-Akt/protein kinase B pathway mediates Gas6
      induction of scavenger receptor a in immortalized human vascular smooth muscle
      cell line.
AB  - The growth arrest-specific gene 6 encodes a secreted protein, Gas6, which was
      originally identified as the ligand of a receptor, Axl, with tyrosine kinase
      activity. The class A scavenger receptor (SRA) mediates lipid uptake into cells,
      leading to the formation of foam cells, an important step in atherogenesis.
      Although Gas6 induces SRA expression, the underlying mechanism is not clear. In
      this report, we show that the Gas6-induced expression of SRA was mediated by the
      phosphatidylinositol 3-OH kinase (PI3-kinase)-serine/threonine kinase
      (Akt/protein kinase B [PKB]) pathway involving Akt phosphorylation. This pathway
      was activated by exposure to Gas6. Furthermore, the effect of Gas6 was abrogated
      by wortmannin, a specific inhibitor of PI3-kinase. We also demonstrated that the
      constitutively active form of Akt enhanced activity of the SRA promoter but that
      the dominant-negative mutant of Akt completely abolished the expression of SRA
      after treatment with Gas6. These results show that the PI3-kinase-Akt/PKB pathway
      participates in Gas6-induced SRA expression and suggests that the activation of
      Akt/PKB plays an important role in Gas6-induced atherosclerosis and foam cell
      formation in human vascular smooth muscle cells.

PMID- 11597932
TI  - Chronic blockade of endothelin receptors improves ischemia-induced angiogenesis
      in rat hindlimbs through activation of vascular endothelial growth factor-no
      pathway.
AB  - This study investigated in vivo the putative angiogenic role of endothelin (ET)-1
      in a model of ischemia-induced angiogenesis. Ischemia was produced by unilateral
      femoral artery occlusion in Wistar rats submitted to either chronic ET-1 infusion
      (2 nmol. kg(-1). min(-1)) or to a dual ET(A)/ET(B) receptor antagonist (bosentan,
      100 mg. kg(-1). d(-1)) for 3 and 28 days. Arterial density was evaluated by
      microangiography and measurement of capillary and arteriolar density in hindlimb
      muscles. ET-1 infusion had no effect on ischemia-induced angiogenesis and was
      associated with a slight decrease in vascular endothelial growth factor (VEGF)
      content measured by Western blot analysis. Conversely, bosentan induced a marked
      increase in vessel density at 3 and 28 days (1.4-fold and 1.7-fold, respectively,
      compared with no treatment; P<0.05), which was associated with an increase in
      VEGF and endothelial NO synthase levels in ischemic legs (by 31+/-8% and 45+/
      23%, respectively, at 3 days and by 65+/-13% and 55+/-15%, respectively, at 28
      days; P<0.05 versus nontreated rats). At day 28, the proangiogenic effect of
      bosentan was abolished when NO synthesis inhibitor N(G)-nitro-L-arginine methyl
      ester (10 mg. kg(-1). d(-1)) or VEGF-neutralizing antibody (2.5 micro/kg twice a
      week) were coadministered with bosentan. Those results provide the first evidence
      of an early and sustained proangiogenic effect of endothelin antagonism
      associated with an upregulation of VEGF and endothelial NO synthase in vivo.

PMID- 11597933
TI  - L-arginine administration reduces neointima formation after stent injury in rats
      by a nitric oxide-mediated mechanism.
AB  - The clinical outcome of vascular stenting is limited by in-stent stenosis.
      Increased nitric oxide (NO)/cGMP signaling by L-arginine (L-Arg) supplementation,
      the substrate for NO synthase (NOS), or NOS gene transfer may reduce in-stent
      neointima formation. After stenting, vascular cell proliferation in rat carotid
      arteries, as measured by 5'-bromodeoxyuridine (5'-BrdU) incorporation, indicated
      15+/-8%, 28+/-5%, and 33+/-7% 5'-BrdU-positive vascular cells at 4, 7, and 14
      days, respectively. Reporter beta-galactosidase gene transfer efficacy was
      evidenced by 30% beta-galactosidase-expressing medial smooth muscle cells at 14
      days. The intima-to-media ratio (I/M) progressively increased to 2.32+/-0.24 at
      14 days. To target in-stent neointima formation, animals were infected with
      adenoviral vectors (4x10(10) plaque-forming units per mL) expressing NOS2
      (AdNOS2) or no transgene (AdRR5), or they received daily doses of L-Arg (500 mg.
      kg(-1). (d-1) IP). The neointima at 14 days was smaller in L-Arg-treated than in
      untreated rats (I/M 1.25+/-0.35 vs 2.32+/-0.24, P<0.05, n=7 each) or in AdRR5-
      and AdNOS2-infected rats (I/M 2.57+/-0.43, n=7 and 1.82+/-0.75, n=8,
      respectively; P<0.05 for both). The effect of L-Arg was abolished by simultaneous
      administration of N(G)-nitro L-arginine methyl ester, an NOS inhibitor (2.03+/
      0.39, P<0.05, vs L-Arg). Inflammation was markedly less in L-Arg- and AdNOS2
      treated than in AdRR5-infected rats. Supplemental L-Arg reduces neointima
      formation after stenting by way of an NOS-dependent mechanism and may be a
      valuable strategy to target in-stent stenosis.

PMID- 11597934
TI  - Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin
      D.
AB  - The present experiments were carried out to test the hypothesis that arterial
      calcification is linked to bone resorption by determining whether the selective
      inhibition of bone resorption with osteoprotegerin will inhibit arterial
      calcification. In the first test, arterial calcification was induced by treating
      22-day-old male rats with warfarin, a procedure that inhibits the gamma
      carboxylation of matrix Gla protein and causes extensive calcification of the
      arterial media. Compared with rats treated for 1 week with warfarin alone, rats
      treated with warfarin plus osteoprotegerin at a dose of 1 mg/kg per day had
      dramatically reduced alizarin red staining for calcification in the aorta and in
      the carotid, hepatic, mesenteric, renal, and femoral arteries, and they had 90%
      lower levels of calcium and phosphate in the abdominal aorta (P<0.001) and in
      tracheal ring cartilage (P<0.01). More rapid arterial calcification was induced
      by treating 49-day-old male rats with toxic doses of vitamin D. Treatment for 96
      hours with vitamin D caused widespread alizarin red staining for calcification in
      the aorta and the femoral, mesenteric, hepatic, renal, and carotid arteries, and
      osteoprotegerin completely prevented calcification in each of these arteries and
      reduced the levels of calcium and phosphate in the abdominal aorta to control
      levels (P<0.001). Treatment with vitamin D also caused extensive calcification in
      the lungs, trachea, kidneys, stomach, and small intestine, and treatment with
      osteoprotegerin reduced or prevented calcification in each of these sites.
      Measurement of serum levels of cross-linked N-teleopeptides showed that
      osteoprotegerin dramatically reduced bone resorption activity in each of these
      experiments (P<0.001). Therefore, we conclude that doses of osteoprotegerin that
      inhibit bone resorption are able to potently inhibit the calcification of
      arteries that is induced by warfarin treatment and by vitamin D treatment. These
      results support the hypothesis that arterial calcification is linked to bone
      resorption.

PMID- 11597935
TI  - Relationship of clinical presentation and calcification of culprit coronary
      artery stenoses.
AB  - Coronary artery calcification is increased in the presence of atherosclerosis.
      However, there is great variability in the calcification of individual coronary
      stenoses, and the clinical significance of this finding remains unknown. We
      tested the hypothesis that culprit lesions associated with myocardial infarction
      or unstable angina are less calcified than are stenoses associated with stable
      angina. The study consisted of 78 patients who underwent intravascular ultrasound
      imaging of culprit stenoses after the placement of a stent. Seventeen patients
      presented with stable angina; 43, with unstable angina; and 18, with myocardial
      infarction. The extent of coronary calcification was measured by the angle of its
      arc and was quantified with a computer-based protractor. The arc of calcium was
      measured in the stented area at the point of maximal calcification and also as an
      average of the calcification found at proximal, middle, and distal stent
      segments. The maximal arc of calcium decreased progressively from patients with
      stable angina (91+/-10 degrees ) to those with unstable angina (59+/-8 degrees )
      and to those with myocardial infarction (49+/-11 degrees, P=0.014). Similarly,
      the average arc of calcium was greatest (32+/-7 degrees ) in patients with stable
      angina, less (15+/-4 degrees ) in patients with unstable angina, and least (10+/
      5 degrees ) in patients with acute myocardial infarction (P=0.014). These
      associations remained significant after adjustment for other factors that
      potentially affect arterial calcification. Acute coronary syndromes are
      associated with a relative lack of calcium in the culprit stenoses compared with
      stenoses of patients with stable angina. These findings have implications for the
      understanding of the biology of acute coronary syndromes as well as for the
      identification of coronary stenoses by methods that rely solely on the presence
      of calcium.

PMID- 11597936
TI  - Effects of prolonged intensive lipid-lowering therapy on the characteristics of
      carotid atherosclerotic plaques in vivo by MRI: a case-control study.
AB  - High-resolution magnetic resonance imaging (MRI) with flow suppression not only
      provides useful information on luminal and wall areas of the carotid artery but
      also can identify the principal tissue components of the carotid atherosclerotic
      plaque. The effects of intensive lipid-lowering therapy on these MRI tissue
      characteristics were examined in patients with coronary disease (CAD). Eight CAD
      patients who have been receiving intensive lipid-lowering treatment (niacin 2.5
      g/d, lovastatin 40 mg/d, and colestipol 20 g/d) for 10 years in the Familial
      Atherosclerosis Treatment Study (FATS) follow-up were randomly selected from
      among 60 such treated patients. Eight CAD patients who were matched to the
      treated patients for age (+/-3 years), baseline low density lipoprotein (+/-5
      mg/dL), and triglycerides (+/-50 mg/dL) but who had never been treated with lipid
      lowering drugs were selected as controls. For each of these 32 carotid arteries,
      luminal and plaque areas were measured by planimetry, in a blinded protocol, from
      the magnetic resonance image that showed most plaque. Fibrous tissue, calcium,
      and lipid deposits were identified on the basis of established criteria. Plaque
      composition was estimated as a fraction of total planimetered area. Patients
      treated with 10-year intensive lipid-lowering therapy, compared with control
      subjects, had significantly lower low density lipoprotein cholesterol levels (84
      versus 158 mg/dL, respectively; P<0.001) and higher high density lipoprotein
      cholesterol levels (51 versus 37 mg/dL, respectively; P<0.001). As a group,
      treated patients, compared with untreated control subjects, had a smaller core
      lipid area (0.7 versus 10.2 mm(2), respectively; P=0.01) and lipid composition
      (1% versus 17%, respectively). Group differences in luminal area (55 [treated]
      versus 44 [control] mm(2), P=NS) and plaque area (58 [treated] versus 64
      [control] mm(2), P=NS) tended to favor treatment. MRI appears useful for
      estimating carotid plaque size and composition. Hyperlipidemic CAD patients
      frequently (97%) have at least moderate (>/=40% area stenosis) carotid plaque. In
      this case-control study, prolonged intensive lipid-lowering therapy is associated
      with a markedly decreased lipid content, a characteristic of clinically stable
      plaques.

PMID- 11597937
TI  - Raman spectroscopic evaluation of the effects of diet and lipid-lowering therapy
      on atherosclerotic plaque development in mice.
AB  - Quantitative characterization of atherosclerotic plaque composition with standard
      histopathological methods remains limited to sectioned plaques. Raman
      spectroscopy enables nondestructive quantification of atherosclerotic plaque
      composition. We used Raman spectroscopy to study the effects of diet and lipid
      lowering therapy on plaque development in apolipoprotein (APO) E*3-Leiden
      transgenic mice. Raman spectra were obtained over the full width and entire
      length of the ascending aorta and aortic arch. Spectra were modeled to calculate
      the relative dry weights of cholesterol and calcium salts, and quantitative maps
      of their distribution were created. In male mice (n=20) that received a high
      fat/high-cholesterol (HFC) diet for 0, 2, 4, or 6 months, Raman spectroscopy
      showed good correlation between cholesterol accumulation and total serum
      cholesterol exposure (r approximately 0.87, P<0.001). In female mice (n=10) that
      were assigned to an HFC diet, with or without 0.01% atorvastatin, a strong
      reduction in cholesterol accumulation (57%) and calcium salts (97%) (P<0.01) was
      demonstrated in the atorvastatin-treated group. In conclusion, Raman spectroscopy
      can be used to quantitatively study the size and distribution of depositions of
      cholesterol and calcification in APOE*3-Leiden transgenic mice. This study
      encourages Raman spectroscopy for the quantitative investigation of
      atherosclerosis and lipid-lowering therapy in larger animals or humans in vivo.

PMID- 11597938
TI  - Effect of statins on bone mineral density and bone histomorphometry in rodents.
AB  - Statins have been postulated to affect bone metabolism. We investigated the
      effects of different doses of simvastatin (1, 5, 10, and 20 mg. kg(-1). d(-1)),
      atorvastatin (2.5 mg. kg(-1). d(-1)), and pravastatin (10 mg. kg(-1). d(-1))
      administered orally for 12 weeks to intact female Sprague-Dawley rats and the
      effect of 20 mg. kg(-1). d(-1) simvastatin in sham-operated and ovariectomized
      rats on femoral bone mineral density (BMD) and quantitative bone histomorphometry
      (QBH) and compared them with controls. BMD was decreased by 1 mg. kg(-1). d(-1)
      simvastatin (P=0.042), atorvastatin (P=0.0002), and pravastatin (P=0.002). The
      effect on QBH parameters differed with different doses of simvastatin (ANOVA,
      P=0.00012). QBH parameters of both bone formation and resorption were
      equivalently and markedly increased by 20 mg. kg(-1). d(-1) simvastatin in 2
      separate groups of intact rats and were reflected by a relatively unchanged BMD.
      At lower doses, 1 mg. kg(-1). d(-1) simvastatin decreased bone formation while
      increasing bone resorption, as reflected by a marked decrease in BMD.
      Ovariectomized animals receiving 20 mg. kg(-1). d(-1) simvastatin showed no
      change in BMD relative to the untreated, ovariectomized controls; their increase
      in bone formation was smaller than in sham-operated rats receiving simvastatin,
      and there was no change in bone resorption. Dose-response curves of simvastatin
      for bone formation and resorption differed. These studies indicate that (1)
      statins decrease BMD in rodents, (2) high-dose simvastatin increases bone
      formation and resorption, (3) low-dose simvastatin decreases bone formation and
      increases bone resorption, (4) the effects of simvastatin on QBH differ at
      different dosages, (5) the effects of simvastatin seen in intact rats are not
      observed in ovariectomized rats, and (6) simvastatin is unable to prevent bone
      loss caused by ovariectomy.

PMID- 11597939
TI  - Markedly elevated lipid transfer inhibitor protein in hypercholesterolemic
      subjects is mitigated by plasma triglyceride levels.
AB  - Lipid transfer inhibitor protein (LTIP, apolipoprotein F) regulates the
      interaction of cholesteryl ester transfer protein (CETP) with lipoproteins and is
      postulated to enhance the ability of CETP to stimulate reverse cholesterol
      transport. The factors that regulate LTIP levels and control its biosynthesis are
      unknown. Here, we demonstrate that plasma LTIP is dramatically increased (3-fold)
      in hypercholesterolemic subjects with normal to mildly elevated plasma
      triglyceride (TG) levels compared with control subjects. LTIP in these subjects
      is not correlated with the extent of hypercholesterolemia or with low density
      lipoprotein (LDL), high density lipoprotein, or CETP levels. However, unlike
      CETP, LTIP levels correlate negatively with plasma TG levels. This association
      does not appear to reflect decreased LTIP synthesis, inasmuch as conditions that
      stimulate TG synthesis and secretion (200 micromol/L oleate) do not reduce LTIP
      secretion by SW872 or Caco-2 cells. In contrast, native or acetyl LDL stimulates
      LTIP secretion 2-fold. Importantly, although plasma LTIP typically resides on
      LDL, up to 25% of LTIP is bound to very low density lipoprotein when this
      lipoprotein is enriched in cholesteryl esters, as occurs in hypercholesterolemia.
      In summary, LTIP levels are markedly elevated by hypercholesterolemia; however,
      plasma TG levels attenuate this response. We hypothesize that this arises from an
      increased association of LTIP with very low density lipoprotein, leading to a
      more rapid clearance of the inhibitor from circulation.

PMID- 11597940
TI  - Cholesterol absorption, synthesis, and fecal output in postmenopausal women with
      and without coronary artery disease.
AB  - Hypercholesterolemia is a prominent risk factor for coronary artery disease
      (CAD), yet cholesterol metabolism has not been evaluated in women with CAD. The
      objective of this study was to determine the interrelations of CAD, serum
      squalene and sterols, and cholesterol metabolism with each other in
      postmenopausal women. For this purpose, we measured serum squalene and sterols
      and fecal steroids (cholesterol and bile acids) and squalene by gas-liquid
      chromatography and evaluated cholesterol absorption and synthesis in
      postmenopausal women with CAD (n=29) and age-matched controls (n=20). On similar
      dietary lipid intake, the cholesterol absorption efficiency and mean serum
      cholesterol level were comparable, but the squalene-to-cholesterol ratio was
      higher in cases than in controls. The presence of CAD was inversely associated
      with fecal total steroids (logistic regression coefficient beta/SE=-2.11, P=0.04)
      and cholesterol synthesis (beta/SE=-2.14, P=0.04) and turnover (beta/SE=-2.19,
      P=0.03) after adjustment for dietary cholesterol, family history of CAD, smoking,
      low and high density lipoprotein cholesterol, and serum triglyceride levels. A
      high serum squalene ratio was not related to cholesterol synthesis but was
      inversely related to fecal squalene excretion, which was lower in cases than in
      controls. In conclusion, the presence of CAD in postmenopausal women is
      independently associated with altered cholesterol metabolism, as reflected by low
      synthesis and inefficient elimination of cholesterol.

PMID- 11597941
TI  - Insulin inhibits the maturation phase of VLDL assembly via a phosphoinositide 3
      kinase-mediated event.
AB  - LY 294002 (80 micromol/L), an inhibitor of phosphoinositide 3-kinase, was used to
      investigate the involvement of this enzyme in the insulin-mediated regulation of
      very low density lipoprotein (VLDL) apolipoprotein B (apoB) output from cultured
      rat hepatocytes. Newly synthesized apoB was pulse-labeled with [(35)S]methionine
      and was then allowed to assemble, via an intermediate precursor stage, into
      mature VLDL during subsequent chase periods. Brefeldin A (BFA, 0.2 microgram/mL)
      was used to discriminate between the role of insulin in the regulation of the
      early, compared with the later, events of VLDL assembly, including apoB
      degradation. Insulin (78 nmol/L), when present during the pulse-labeling and
      subsequent chase periods, inhibited the secretion of apoB-100 and apoB-48 as VLDL
      by 53% and 56%, respectively. Degradation of both was concomitantly increased.
      Secretion of high density lipoprotein apoB, derived from VLDL precursors, was
      relatively unaffected under these conditions, as was the net synthesis of apoB
      100 and apoB-48. The presence of BFA during the pulse-labeling period and
      subsequent chase period prevented the maturation of VLDL in the insulin-treated
      and the non-insulin-treated cells. BFA was then removed, allowing the maturation
      of VLDL to proceed. Removal of insulin at this stage reversed the overall
      inhibitory effect of insulin. Furthermore, when insulin remained present during
      this period, the simultaneous presence of LY 294002 also reversed the inhibitory
      effect of insulin on VLDL apoB output and abolished the increase in apoB
      degradation. The results suggest that insulin signaling via phosphoinositide 3
      kinase inhibited the maturation phase of VLDL assembly by preventing bulk lipid
      transfer to a VLDL precursor, thus enhancing the degradation of apoB. There was
      no inhibition of the conversion of newly synthesized apoB into the VLDL precursor
      form.

PMID- 11597942
TI  - Adhesion of monocytes to arterial endothelium and initiation of atherosclerosis
      are critically dependent on vascular cell adhesion molecule-1 gene dosage.
AB  - - Vascular cell adhesion molecule-1 (VCAM-1/Vcam1) is a cytokine-inducible member
      of the immunoglobulin gene superfamily that is expressed by arterial endothelial
      cells in regions predisposed to atherosclerosis and at borders of atherosclerotic
      plaques. To determine whether VCAM-1 expression regulates atherosclerotic lesion
      formation, we crossed Vcam1 domain 4-deficient (D4D) mice, which partially
      circumvent the embryonic lethality of Vcam1 null mice, with apolipoprotein E null
      (Apoe(-/-)) mice, which spontaneously develop hypercholesterolemia and
      atherosclerosis. In the Apoe(-/-) background, mice homozygous for the Vcam1 D4D
      allele had markedly reduced arterial VCAM-1 expression, monocyte adherence in the
      aortic root, and fatty streak formation. Heterozygous Vcam1 D4D mice revealed a
      Vcam1 gene-dosage effect and had intermediate, yet significant, reductions in
      these parameters. Our data demonstrate that VCAM-1 plays a pivotal role in the
      initiation of atherosclerosis in Apoe(-/-) mice.

PMID- 11597943
TI  - Association between P-selectin gene polymorphisms and soluble P-selectin levels
      and their relation to coronary artery disease.
AB  - P-selectin is a cellular adhesion molecule that mediates the interaction of
      activated endothelial cells or platelets with leukocytes. Increased levels of
      soluble P-selectin have been reported in various cardiovascular disorders. We
      measured serum soluble P-selectin levels as well as 3 polymorphisms of the P
      selectin gene (C-2123G, A-1969G, and Thr715Pro) in a large cohort of patients
      with documented coronary artery disease (n=869) and a healthy control group
      (n=334). The 3 P-selectin polymorphisms were strongly associated with P-selectin
      levels and altogether explained 7.3% and 18.6% of the P-selectin variability in
      patients and controls, respectively. Genotype distributions did not significantly
      differ between patients and controls. P-selectin levels were increased in
      patients younger than 55 years of age compared with controls (135.2 vs 114.3
      ng/mL, P<0.01). On the contrary, patients older than 65 years of age had
      significantly lower P-selectin levels than did controls (121.5 vs 134.7 ng/mL,
      P<0.02). In intermediate age groups, P-selectin levels did not significantly
      differ between the 2 groups. In conclusion, this study revealed a strong
      association between P-selectin gene polymorphisms and serum P-selectin levels and
      a complex age-dependent relation between soluble P-selectin levels and coronary
      artery disease, which suggests that this molecule might have different roles in
      the atherothrombotic process.

PMID- 11597944
TI  - Effect of gamma-irradiation and bone marrow transplantation on atherosclerosis in
      LDL receptor-deficient mice.
AB  - Bone marrow transplantation (BMT) is commonly used to study the participation of
      bone marrow-derived cells in atherosclerosis. To determine the effect of this
      methodology on lesions, 16 male low density lipoprotein (LDL) receptor knockout
      (LDLr-/-) mice were reconstituted with bone marrow from syngeneic LDLr-/- mice
      after 10 Gy gamma-irradiation and compared with 12 male LDLr-/- littermates that
      did not undergo BMT (no-BMT group). Mice were fed a high fat diet (HFD) for 16
      weeks to induce atherosclerosis. Sixteen additional LDLr-/- mice underwent BMT,
      and 12 male LDLr-/- mice that did not undergo BMT were fed a chow diet for 56
      weeks. Thoracic aorta lesion areas were smaller in BMT mice than in no-BMT mice
      fed the HFD (P<0.0001). In contrast, aortic root lesion areas were greater in the
      BMT mice fed the HFD (P<0.0001) as well as in those fed the chow diet (P=0.0001).
      Abdominal aorta free cholesterol and cholesteryl ester mass were minimal in all
      groups studied. Aortic root lesions from all no-BMT mice were densely collagenous
      and encapsulated by a cellular cap, whereas lesions in the BMT mice contained
      lipid cores and minimal collagen staining. Although the reason for these
      differences in lesion size and composition remains unresolved, this study
      suggests that multiple parameters of lesion formation should be examined to
      assess atherosclerosis.

PMID- 11597945
TI  - Role of arterial wall antioxidant defense in beneficial effects of exercise on
      atherosclerosis in mice.
AB  - The mechanism(s) by which exercise reduces atherogenic risk remains unknown. This
      study tested the hypothesis that sustained exercise-induced oxidative stress may
      increase antioxidant defense in the arterial wall. Acute exercise induced an
      increase in antibodies to oxidatively modified proteins and catalase in the
      aortic walls of normal mice compared with sedentary control mice. In male
      atherogenic diet-fed low density lipoprotein (LDL) receptor-deficient mice,
      exercise lowered plasma cholesterol (15%) and decreased atherosclerotic lesions
      by 40% compared with values in sedentary control mice, with a concomitant
      increase in arterial catalase and endothelial NO synthase. Because these mice
      lack the LDL receptor, the results indicate that the LDL receptor might not be
      responsible for the exercise-induced lowering of plasma cholesterol. Vitamin E
      supplementation to exercising LDL receptor-deficient mice did not reduce
      atherosclerotic lesion formation significantly as opposed to lesion formation in
      untreated exercised mice. Moreover, vitamin E counteracted the beneficial effects
      of exercise by preventing the induction of aortic catalase activity and
      endothelial NO synthase expression. These results might indicate that although
      vitamin E might have prevented the exercise-induced oxidative stress, its
      availability in the artery was insufficient to prevent the atherosclerotic
      process. These results indicate that exercise-induced plasma oxidative stress
      could be responsible for the prevention of atherosclerosis by stimulating
      arterial antioxidant response. Furthermore, vitamin E supplementation could be
      deleterious in exercisers by inhibiting antioxidant enzyme buildup in the
      arterial wall.

PMID- 11597946
TI  - Thrombin upregulates tissue transglutaminase in endothelial cells: a potential
      role for tissue transglutaminase in stability of atherosclerotic plaque.
AB  - Atherosclerosis is characterized by thickening of the vessel wall, smooth muscle
      cell proliferation, macrophage infiltration, and deposition of a fibrin network.
      Transglutaminases are a family of enzymes catalyzing the formation of stable
      covalent cross-links between proteins. Here, we show that tissue transglutaminase
      (tTG) synthesis by human umbilical vein endothelial cells is upregulated by
      thrombin, the serine protease that causes fibrin formation and many cellular
      inflammatory effects. Thrombin upregulated tTG 2-fold at the mRNA and protein
      level. Cellular cross-linking activity was increased to an even greater extent;
      antibody to tTG neutralized the increased activity. The effect on tTG expression
      required active thrombin and was mediated mainly through protease-activated
      receptor-1, a thrombin receptor. Increased tTG antigen and activity were evident
      in human umbilical vein endothelial cells and extracellular matrix in situ.
      Thrombin treatment also led to a cellular redistribution of tTG. Normal vessel
      wall stained positively for tTG in the smooth muscle cells and in the
      subendothelium. The intensity of staining increased in vessel walls with plaque,
      where there was a striking increase in tTG in the smooth muscle cells immediately
      below the plaque. These studies indicate a role for tTG in the stabilization of
      atherosclerotic plaques and suggest that its local expression can be controlled
      by thrombin.

PMID- 11597947
TI  - Phosphatidylethanolamine participates in the stimulation of the contact system of
      coagulation by very-low-density lipoproteins.
AB  - We have analyzed the influence of plasma lipoproteins on the activation of the
      contact pathway of blood coagulation in platelet-rich plasma (PRP). The formation
      of thrombin in PRP incubated in vitro was abolished by the factor XIIa antagonist
      corn trypsin inhibitor and by severe factor XII deficiency, indicating mediation
      by the contact system. Addition of VLDL to the PRP shortened the lag period and
      increased the generation of thrombin. There was no effect of HDL and LDL. In
      whole blood, VLDL accelerated the rate of fibrin formation, the procoagulant
      effect being prevented by factor XII deficiency and by corn trypsin inhibitor.
      The thrombin formation in the PRP was strongly increased by microemulsions of the
      VLDL lipids while it was reduced by the aqueous phase of the particles.
      Separation of the VLDL lipids indicated the phospholipid component as the major
      activating principle. Vesicles supplemented with all VLDL phospholipids but
      lacking specifically the fraction containing phosphatidylethanolamine (PE)
      prolonged the lag time. The PE containing fraction alone as well as vesicles
      enriched with egg PE shortened the lag period. In summary, VLDL stimulates the
      contact pathway of blood coagulation, ethanolamine phospholipids being the most
      active components of the particles.

PMID- 11597948
TI  - Plasma fibrin D-dimer levels and risk of stable coronary artery disease: results
      of a large case-control study.
AB  - Increased levels of fibrin D-dimer are indicative of a hypercoagulable state, as
      found in acute coronary syndromes. Few well-controlled studies have assessed D
      dimers in patients with stable coronary artery disease (CAD). We measured levels
      of D-dimers (in ng/mL by enzyme-linked immunosorbent assay) in 312 patients with
      angiographically proved CAD and stable angina pectoris and in 477 age- and sex
      matched healthy blood donors. Demographic characteristics were assessed by a
      standardized questionnaire, and a complete lipid profile was performed for all
      subjects. In addition, a variety of other markers of hemostasis and inflammation
      were measured. The distribution of D-dimer levels was skewed to the right, and
      plasma median levels were higher in cases than in controls (median: 11.2 vs 2.8
      ng/mL; P<0.001). In controls, correlations of D-dimer were found with fibrinogen,
      plasma viscosity, and interleukin-6. In logistic regression analysis, the age-
      and sex-adjusted odds ratio (OR) for the presence of CAD was 2.6 (95% confidence
      interval [CI], 1.9 to 3.5) when the highest quartile of the D-dimer distribution
      was compared with the combined lower 3 quartiles. The OR did not change
      appreciably after controlling for nonlipid risk factors (OR, 2.7; 95% CI, 1.9 to
      3.9) and remained significant after further adjustment for other hemostatic
      parameters (OR, 2.4; 95% CI, 1.7 to 3.3) and markers of inflammation (OR, 2.1;
      95% CI, 1.5 to 2.9). Plasma D-dimer levels are strongly and independently
      associated with the presence of CAD in patients with stable angina pectoris.
      These results support the concept of a contribution of intravascular fibrin to
      atherothrombogenesis.

PMID- 11597949
TI  - Bioavailability of vitamin E as function of food intake in healthy subjects:
      effects on plasma peroxide-scavenging activity and cholesterol-oxidation
      products.
AB  - Clinical trials with vitamin E have yielded contrasting results. In these trials,
      the amount of vitamin E given was different, and the compliance was not assessed
      in all studies. In addition, the modality of intake, ie, in relation to food, was
      not specified in any trial. Vitamin E is lipophilic, and its absorption is
      expected to be increased by food. We studied the bioavailability of vitamin E in
      relation to food intake and the effect on the lipid peroxide-scavenging activity
      of plasma and on 7beta-hydroxycholesterol and 7-ketocholesterol (oxysterols) as
      markers of oxidant stress. Twenty healthy Italian subjects were randomly assigned
      to take vitamin E at 300 mg/d on an empty stomach (group A) or during dinner
      (group B) for 15 days. Plasma vitamin E markedly increased in group B (84%)
      compared with group A (29%). The lipid peroxide-scavenging activity of plasma
      increased significantly in group B (14%, P=0.005) but did not change in group A.
      All subjects showed very low levels of plasma oxysterols, which were not affected
      by vitamin E supplementation in either group. This study shows that plasma
      concentration of vitamin E and plasma antioxidant activity in response to oral
      supplementation are markedly affected by food intake. Healthy Italian subjects
      show very low levels of cholesterol oxidation products; these low levels are
      possibly related to the Mediterranean diet. To obtain maximal absorption, vitamin
      E must be given at meals. These data should be taken into account in clinical
      trials with vitamin E.

PMID- 11597950
TI  - Dying for a drink. Global suicide prevention should focus more on alcohol use
      disorders.

PMID- 11597951
TI  - Surveillance for infectious diseases in the European Union. A small European
      centre may have an important coordinating role.

PMID- 11597952
TI  - Cardiopulmonary resuscitation in adults. Revised guidelines are more evidence
      based.

PMID- 11597953
TI  - Revisiting the Cochrane Collaboration. Meeting the challenge of Archie Cochrane-
      and facing up to some new ones.

PMID- 11597954
TI  - Reacting to terrorism. The response should be through law not war.

PMID- 11597956
TI  - Stop military strikes and ship in aid, doctors say.

PMID- 11597960
TI  - World Medical Association clarifies rules on placebo controlled trials.

PMID- 11597961
TI  - Government pulls plug on regional research and development funding.

PMID- 11597962
TI  - AIDS in a "state of flux" in Asia, says UN report.

PMID- 11597963
TI  - US doctors say sex selection acceptable for non-medical reasons.

PMID- 11597964
TI  - Drug companies defrauded Medicare of millions.

PMID- 11597965
TI  - Quality of Cochrane reviews: assessment of sample from 1998.
AB  - OBJECTIVE: To assess the quality of Cochrane reviews. DESIGN: Ten methodologists
      affiliated with the Cochrane Collaboration independently examined, in a
      semistructured way, the quality of reviews first published in 1998. Each review
      was assessed by two people; if one of them noted any major problems, they agreed
      on a common assessment. Predominant types of problem were categorised. SETTING:
      Cyberspace collaboration coordinated from the Nordic Cochrane Centre. STUDIES:
      All 53 reviews first published in issue 4 of the Cochrane Library in 1998. MAIN
      OUTCOME MEASURE: Proportion of reviews with various types of major problem.
      RESULTS: No problems or only minor ones were found in most reviews. Major
      problems were identified in 15 reviews (29%). The evidence did not fully support
      the conclusion in nine reviews (17%), the conduct or reporting was unsatisfactory
      in 12 reviews (23%), and stylistic problems were identified in 12 reviews (23%).
      The problematic conclusions all gave too favourable a picture of the experimental
      intervention. CONCLUSIONS: Cochrane reviews have previously been shown to be of
      higher quality and less biased on average than other systematic reviews, but
      improvement is always possible. The Cochrane Collaboration has taken steps to
      improve editorial processes and the quality of its reviews. Meanwhile, the
      Cochrane Library remains a key source of evidence about the effects of healthcare
      interventions. Its users should interpret reviews cautiously, particularly those
      with conclusions favouring experimental interventions and those with many
      typographical errors.

PMID- 11597966
TI  - Use of systematic reviews in clinical practice guidelines: case study of smoking
      cessation.
AB  - OBJECTIVE: To examine the extent to which recommendations in the national
      guidelines for the cessation of smoking are based on evidence from systematic
      reviews of controlled trials. DESIGN: Retrospective analysis of recommendations
      for the national guidelines for the cessation of smoking. MATERIALS: National
      guidelines in clinical practice on smoking cessation published in English. MAIN
      OUTCOME MEASURES: The type of evidence (systematic review of controlled trials,
      individual trials, other studies, expert opinion) used to support each
      recommendation. We also assessed whether a Cochrane systematic review was
      available and could have been used in formulating the recommendation. RESULTS:
      Four national smoking cessation guidelines (from Canada, New Zealand, the United
      Kingdom, and the United States) covering 105 recommendations were identified. An
      explicit evidence base for 100%, 89%, 68%, and 98% of recommendations,
      respectively, was detected, of which 60%, 56%, 59%, and 47% were based on
      systematic reviews of controlled studies. Cochrane systematic reviews could have
      been used to develop between 39% and 73% of recommendations but were actually
      used in 0% to 36% of recommendations. The UK guidelines had the highest
      proportion of recommendations based on Cochrane systematic reviews. CONCLUSIONS:
      Use of systematic reviews in guidelines is a measure of the "payback" on
      investment in research synthesis. Systematic reviews commonly underpinned
      recommendations in guidelines on smoking cessation. The extent to which they were
      used varied by country and there was evidence of duplication of effort in some
      areas. Greater international collaboration in developing and maintaining an
      evidence base of systematic reviews can improve the efficiency of use of research
      resources.

PMID- 11597967
TI  - Communication about sexual problems and sexual concerns in ovarian cancer:
      qualitative study.

PMID- 11597968
TI  - Ethical debate: Vaccination against mumps, measles, and rubella: is there a case
      for deepening the debate? How safe is MMR vaccine?

PMID- 11597969
TI  - Acute asthma.

PMID- 11597970
TI  - Evidence based well child care.

PMID- 11597971
TI  - ABC of the upper gastrointestinal tract. Dysphagia.

PMID- 11597972
TI  - The case against aggressive treatment of type 2 diabetes: critique of the UK
      prospective diabetes study.

PMID- 11597973
TI  - New variant Creutzfeldt-Jakob disease: the epidemic that never was.

PMID- 11597974
TI  - Communicable disease outbreaks involving more than one country: systems approach
      to evaluating the response.

PMID- 11597975
TI  - Eligibility criteria for home treatment of DVT vary.

PMID- 11597976
TI  - Reducing sexually transmitted infections among gay men. No doubt should be cast
      on efficacy of cognitive behavioural interventions.

PMID- 11597977
TI  - Healthcare professionals must be perceived as caring.

PMID- 11597978
TI  - Neurosis may be increasing.

PMID- 11597980
TI  - Withdrawal of baclofen may cause acute confusion in elderly patients.

PMID- 11597981
TI  - GPs need guidance on protecting their computers from viruses.

PMID- 11597984
TI  - PI3King the L-type calcium channel activation mechanism.

PMID- 11597985
TI  - Tubes, branches, and pillars: the many ways of forming a new vasculature.

PMID- 11597986
TI  - EDHF and NO: different pathways for production--similar actions.

PMID- 11597987
TI  - Prostaglandin H synthase and vascular function.
AB  - Prostaglandin H synthase (PGHS) is a rate-limiting enzyme in the production of
      prostaglandins and thromboxane, which are important regulators of vascular
      function. Under normal physiological conditions, PGHS-dependent vasodilators
      (such as prostacyclin) modulate vascular tone. However, PGHS-dependent
      vasoconstriction (mediated by thromboxane and/or its immediate precursor, PGH(2))
      predominates in some vascular pathologies (eg, systemic hypertension, diabetes,
      cerebral ischemia, and aging). This review will discuss the role of PGHS
      dependent modulation of vascular function in a number of vascular beds (systemic,
      pulmonary, cerebral, and uterine) with an emphasis on vascular pathophysiology.
      Moreover, the specific contributions of the different isoforms (PGHS-1 and PGHS
      2) are discussed. Understanding the role of PGHS in vascular function is of
      particular importance because they are the targets of the commonly used
      nonsteroidal antiinflammatory drugs (NSAIDs), which include aspirin and
      ibuprofen. Importantly, with the advent of specific PGHS-2 inhibitors for
      treatment of conditions such as chronic inflammatory disease, it is an opportune
      time to review the data regarding PGHS-dependent modulation of vascular function.

PMID- 11597988
TI  - ERK and p38 MAPK, but not NF-kappaB, are critically involved in reactive oxygen
      species-mediated induction of IL-6 by angiotensin II in cardiac fibroblasts.
AB  - We recently reported that angiotensin II (Ang II) induced IL-6 mRNA expression in
      cardiac fibroblasts, which played an important role in Ang II-induced cardiac
      hypertrophy in paracrine fashion. The present study investigated the regulatory
      mechanism of Ang II-induced IL-6 gene expression, focusing especially on reactive
      oxygen species (ROS)-mediated signaling in cardiac fibroblasts. Ang II increased
      intracellular ROS in cardiac fibroblasts, and the increase was completely
      inhibited by the AT-1 blocker candesartan and the NADH/NADPH oxidase inhibitor
      diphenyleneiodonium (DPI). We first confirmed that antioxidant N-acetylcysteine,
      superoxide scavenger Tiron, and DPI suppressed Ang II-induced IL-6 expression.
      Because we observed that exogenous H(2)O(2) also increased IL-6 mRNA, the
      signaling pathways downstream of Ang II and exogenous H(2)O(2) were compared. Ang
      II, as well as exogenous H(2)O(2), activated ERK, p38 MAPK, and JNK, which were
      significantly inhibited by N-acetylcysteine and DPI. In contrast with exogenous
      H(2)O(2), however, Ang II did not influence phosphorylation and degradation of
      IkappaB-alpha/beta or nuclear translocation of p65, nor did it increase NF-kappaB
      promoter activity. PD98059 and SB203580 inhibited Ang II-induced IL-6 expression.
      Truncation and mutational analysis of the IL-6 gene promoter showed that CRE was
      an important cis-element in Ang II-induced IL-6 gene expression. NF-kappaB
      binding site was important for the basal expression of IL-6, but was not
      activated by Ang II. Ang II phosphorylated CREB through the ERK and p38 MAPK
      pathway in a ROS-sensitive manner. Collectively, these data indicated that Ang II
      stimulated ROS production via the AT1 receptor and NADH/NADPH oxidase, and that
      these ROS mediated activation of MAPKs, which culminated in IL-6 gene expression
      through a CRE-dependent, but not NF-kappaB-dependent, pathway in cardiac
      fibroblasts.

PMID- 11597989
TI  - Catalytic oligodeoxynucleotides define a key regulatory role for early growth
      response factor-1 in the porcine model of coronary in-stent restenosis.
AB  - Early growth response factor-1 (Egr-1) controls the expression of a growing
      number of genes involved in the pathogenesis of atherosclerosis and
      postangioplasty restenosis. Egr-1 is activated by diverse proatherogenic stimuli.
      As such, this transcription factor represents a key molecular target in efforts
      to control vascular lesion formation in humans. In this study, we have generated
      DNAzymes targeting specific sequences in human EGR-1 mRNA. These molecules cleave
      in vitro transcribed EGR-1 mRNA efficiently at preselected sites, inhibit EGR-1
      protein expression in human aortic smooth muscle cells, block serum-inducible
      cell proliferation, and abrogate cellular regrowth after mechanical injury in
      vitro. These DNAzymes also selectively inhibit EGR-1 expression and proliferation
      of porcine arterial smooth muscle cells and reduce intimal thickening after
      stenting pig coronary arteries in vivo. These findings demonstrate that
      endoluminally delivered DNAzymes targeting EGR-1 may serve as inhibitors of in
      stent restenosis.

PMID- 11597990
TI  - Proangiogenic effect of angiotensin-converting enzyme inhibition is mediated by
      the bradykinin B(2) receptor pathway.
AB  - Recent studies have suggested a proangiogenic effect of angiotensin-converting
      enzyme (ACE) inhibition. We hypothesized that such a proangiogenic effect of ACE
      inhibition may be mediated, in part, by bradykinin (BK) B(2)-receptor pathway.
      This study therefore examined the neovascularization induced by ACE inhibitor
      treatment in B(2) receptor-deficient mice (B(2)(-/-)) in a model of surgically
      induced hindlimb ischemia. After artery femoral occlusion, wild-type and B(2)(-/
      ) mice were treated with or without ACE inhibitor (perindopril, 3 mg/kg/d) for 28
      days. Angiogenesis was then quantitated by microangiography, capillary density
      measurement, and laser Doppler perfusion imaging. The protein levels of vascular
      endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS)
      were determined by Western blot. In wild-type animals, vessel density and
      capillary number in the ischemic leg were raised by 1.8- and 1.4-fold,
      respectively, in mice treated with ACE inhibitor when compared with the
      nontreated animals (P<0.01). This corresponded to an improved
      ischemic/nonischemic leg perfusion ratio by 1.5-fold in ACE inhibitor-treated
      animals when compared with the untreated ones (0.87+/-0.07 versus 0.59+/-0.05,
      respectively, P<0.01). Activation of the angiogenic process was also associated
      with a 1.7-fold increase in tissue eNOS protein level in mice treated with ACE
      inhibitor (P<0.05 versus control) but not with changes in VEGF protein level.
      Conversely, ACE inhibition did not affect vessel density, blood flow, and eNOS
      protein level in ischemic hindlimb of B(2)(-/-) mice. Therefore, proangiogenic
      effect of ACE inhibition is mediated by B(2)-receptor signaling and was
      associated with upregulation of eNOS content, independently of VEGF expression.

PMID- 11597991
TI  - Rapid reversal of the diabetic endothelial dysfunction by pharmacological
      inhibition of poly(ADP-ribose) polymerase.
AB  - Oxygen- and nitrogen-derived free radicals and oxidants play an important role in
      the pathogenesis of diabetic endothelial dysfunction. Recently we proposed the
      importance of oxidant-induced DNA strand breakage and activation of the nuclear
      enzyme poly(ADP-ribose) polymerase (PARP) in the pathogenesis of diabetic
      endothelial dysfunction. In this study, we tested whether established diabetic
      endothelial dysfunction is reversible by PARP inhibition. The novel PARP
      inhibitor PJ34 (10 mg/kg per day PO) was given at various lengths (4 weeks or 3
      days) for established streptozotocin-diabetic animals. In addition, we also
      tested whether incubation of the aortic rings with PJ34 (3 micromol/L) or a
      variety of other PARP inhibitors for 1 hour affects the diabetic vascular
      changes. Both 4-week and 3-day PARP-inhibitor treatment of streptozotocin
      diabetic mice with established endothelial dysfunction fully reversed the
      acetylcholine-induced endothelium-dependent relaxations in vitro. Furthermore, 1
      hour in vitro incubation of aortae from streptozotocin-diabetic mice with various
      PARP inhibitors was able to reverse the endothelial dysfunction. ATP, NAD(+), and
      NADPH levels were markedly reduced in diabetic animals, and PARP-inhibitor
      treatment was able to restore these alterations. Unexpectedly, pharmacological
      inhibition of PARP not only prevents the development of the endothelial
      dysfunction but is also able to rapidly reverse it. Thus, PARP activation and the
      associated metabolic compromise represent an ongoing process in diabetic blood
      vessels. Pharmacological inhibition of this process is able to reverse diabetic
      endothelial dysfunction.

PMID- 11597992
TI  - Phosphoinositide 3-kinase isoforms selectively couple receptors to vascular L
      type Ca(2+) channels.
AB  - Heterodimeric class I phosphoinositide 3-kinase (PI3K) has been shown to be
      involved in the stimulation of voltage-gated Ca(2+) channels by various
      mediators. In this study, we bring evidences that vascular L-type Ca(2+) channels
      can be modulated by both tyrosine kinase-regulated class Ia and G protein
      regulated class Ib PI3Ks. Purified recombinant PI3Ks increased the peak Ca(2+)
      channel current density when applied intracellularly. Furthermore, PI3Kalpha-,
      beta-, and delta-mediated stimulations of Ca(2+) channel currents were increased
      by preactivation by a phosphotyrosyl peptide, whereas PI3Kgamma- and beta
      mediated effects were increased by Gbetagamma. In freshly isolated and cultured
      vascular myocytes, angiotensin II and Gbetagamma stimulated L-type Ca(2+) channel
      current. In contrast, platelet-derived growth factor (PDGF)-BB and the
      phosphotyrosyl peptide did not stimulate Ca(2+) channel current in freshly
      isolated cells despite the presence of endogenous PDGF receptors and PI3Kalpha
      and PI3Kgamma. Interestingly, when endogenous PI3Kbeta expression arose in
      cultured myocytes, both PDGF and phosphotyrosyl peptide stimulated Ca(2+)
      channels through PI3Kbeta, as revealed by the inhibitory effect of an anti
      PI3Kbeta antibody. These results suggest that endogenous PI3Kbeta but not
      PI3Kalpha is specifically involved in PDGF receptor-induced stimulation of Ca(2+)
      channels and that different isoforms of PI3K regulate physiological increases of
      Ca(2+) influx in vascular myocytes stimulated by vasoconstrictor or growth
      factor.

PMID- 11597993
TI  - On the role of Ca(2+)- and voltage-dependent inactivation in Ca(v)1.2 sensitivity
      for the phenylalkylamine (-)gallopamil.
AB  - L-type calcium channels (Ca(v)1.m) inactivate in response to elevation of
      intracellular Ca(2+) (Ca(2+)-dependent inactivation) and additionally by
      conformational changes induced by membrane depolarization (fast and slow voltage
      dependent inactivation). Molecular determinants of inactivation play an essential
      role in channel inhibition by phenylalkylamines (PAAs). The relative impacts,
      however, of Ca(2+)-dependent and voltage-dependent inactivation in Ca(v)1.2
      sensitivity for PAAs remain unknown. In order to analyze the role of the
      different inactivation processes, we expressed Ca(v)1.2 constructs composed of
      different beta-subunits (beta(1a)-, beta(2a)-, or beta(3)-subunit) in Xenopus
      oocytes and estimated their (-)gallopamil sensitivity by means of the two
      microelectrode voltage clamp with either Ba(2+) or Ca(2+) as charge carrier.
      Ca(v)1.2 consisting of the beta(2a)-subunit displayed the slowest inactivation
      and the lowest apparent sensitivity for the PAA (-)gallopamil. A significantly
      higher apparent (-)gallopamil-sensitivity with Ca(2+) as charge carrier was
      observed for all 3 beta-subunit compositions. The kinetics of Ca(2+)-dependent
      inactivation and slow voltage-dependent inactivation were not affected by drug.
      The higher sensitivity of the Ca(v)1.2 channels for (-)gallopamil with Ca(2+) as
      charge carrier results from slower recovery (tau(rec,Ca) approximately 15 seconds
      versus tau(rec,Ba) approximately 3 to 5 seconds) from a PAA-induced channel
      conformation. We propose a model where (-)gallopamil promotes a fast voltage
      dependent component in Ca(v)1.2 inactivation. The model reproduces the higher
      drug sensitivity in Ca(2+) as well as the lower sensitivity of slowly
      inactivating Ca(v)1.2 composed of the beta(2a)-subunit.

PMID- 11597994
TI  - Aging enhances the sensitivity of endothelial cells toward apoptotic stimuli:
      important role of nitric oxide.
AB  - Advanced aging leads to impaired endothelial NO synthesis and enhanced
      endothelial cell apoptosis; therefore, we investigated the sensitivity of aged
      endothelial cells toward apoptotic stimuli and determined the role of NO. Human
      umbilical vein endothelial cells (HUVECs) were cultured until 14th passage. In
      aged cells, oxLDL and tumor necrosis factor-alpha-induced apoptosis and caspase-3
      like activity were significantly enhanced more than 3-fold compared with young
      cells (passage 3). Because NO contributes to protection against endothelial cell
      death via S-nitrosylation of caspases, we determined endothelial NO synthase
      (eNOS) protein expression and the content of S-nitrosylated proteins. Aged HUVECs
      showed significantly reduced eNOS expression (35+/-10%) and a decrease in the
      overall S-NO content (33+/-3%), suggesting that eNOS downregulation may be
      involved in age-dependent increase of apoptosis sensitivity. Indeed, eNOS
      knockout endothelial cells showed a significantly enhanced apoptosis induction.
      Exogenous NO donors abolished increased apoptosis and caspase-3-like activity. In
      contrast, the application of shear stress, which exerts a profound apoptosis
      inhibitory effect via upregulation of NO synthesis in young cells, failed to
      inhibit apoptosis in aged cells. Moreover, no upregulation of eNOS protein
      expression and S-NO content in response to shear stress was detected in aged
      cells. Overexpression of wild-type eNOS completely restored the antiapoptotic
      effect of shear stress, whereas only a partial inhibitory effect was detected
      under steady conditions. Strikingly, transfection of constitutively active
      phosphomimetic eNOS (S1177D) further abrogated apoptosis in aged HUVECs. Thus,
      aging of endothelial cells is associated with decreased NO synthesis and
      concomitantly increased sensitivity of apoptosis, which may contribute to
      functional impairment of the endothelial monolayer.

PMID- 11597995
TI  - Endothelial G protein beta-subunits trigger nitric oxide-but not endothelium
      derived hyperpolarizing factor-dependent dilation in rabbit resistance arteries.
AB  - A single subtype of heterotrimeric G protein-coupled receptor controls both
      nitric oxide (NO) (sensitive to L-arginine analogues) and endothelium-derived
      hyperpolarizing factor (EDHF) (sensitive to high-external K(+) and apamine)
      production by the vascular endothelium leading to dilation. We hypothesized that
      alpha- and betagamma-subunits of the G protein serve as distinct intermediates to
      produce NO and EDHF. In pressurized resistance arteries, selective pinocytotic
      endothelial incorporation of specific antibodies (Abs) directed against
      alpha(q/11)-subunits abolished acetylcholine (Ach)-mediated dilation but failed
      to influence oxymetazoline (Oxy, alpha(2)-adrenergic receptor agonist)-induced
      dilation. In contrast, alpha(i1-2)-subunit Abs prevented Oxy- but not Ach-induced
      dilation. Thus, as expected, endothelial muscarinic and alpha(2)-adrenoceptors
      couple to G(q) protein and G(i) proteins, respectively. beta-subunit Abs reduced
      both Ach- and Oxy-induced dilation. The beta-subunit Abs abolished the nitro-L
      arginine (L-NNA)-sensitive component but did not impair the high-external K(+)
      sensitive component of the dilation induced by Ach and Oxy. Thus, G protein beta
      subunits primarily accounted for NO production. Neutralization of Hsp90 and
      inhibition of the phospholipase C by U73122 (1 micromol/L) or intracellular
      Ca(2+) buffering with BAPTA-AM (10 micromol/L) sharply reduced NO-dependent but
      not K(+)-sensitive dilation. In conclusion, mobilization of the G protein beta
      subunit is pivotal to NO-dependent dilation triggered through muscarinic and
      alpha(2)-adrenergic receptors. In contrast, receptor-operated EDHF-dependent
      dilation was insensitive to beta-subunit Abs. Although not directly activating
      the NO pathway, alpha-subunit activation is an absolute prerequisite for receptor
      operated endothelium-dependent dilation of resistance arteries.

PMID- 11597996
TI  - Vascular morphogenesis and remodeling in a model of tissue repair: blood vessel
      formation and growth in the ovarian pedicle after ovariectomy.
AB  - To investigate mechanisms of vascular morphogenesis in tissue repair, we
      performed ovariectomy with resection of the corresponding branches of the ovarian
      vessels in nude mice. This induces a vascular network remodeling response in the
      healing ovarian pedicle. Reconstruction of 2000 histological serial sections
      demonstrated that a new vascular network composed of venous-venous loops forms in
      the wall of the dilated ovarian vein. Preexisting veins of all sizes, including a
      branch of the main artery, are subjected to segmentation. Loop formation and
      segmentation are based on intussusceptive microvascular growth. Loop formation is
      followed by elongation. Loop remodeling occurs also by intussusception and
      results in the formation of compound loop systems. All loop systems observed were
      completely patent. Blind-ending sprouts were extremely rare. Anastomoses between
      the preexisting vessels subjected to segmentation and the loop systems were
      established to include the newly formed vessels into the preexisting vascular
      network. The formation of an increasing number of patent loop systems likely
      decreases hypoxia and subsequently arrests angiogenesis with transformation of
      the granulation tissue into a scar. Loop formation also occurred inside a large
      thrombus that occluded a part of the lumen of the main vein.

PMID- 11597997
TI  - Vascular morphogenesis and remodeling in a human tumor xenograft: blood vessel
      formation and growth after ovariectomy and tumor implantation.
AB  - To determine mechanisms of blood vessel formation and growth in solid tumors, we
      used a model in which LS174T human colon adenocarcinomas are grown in the
      isolated ovarian pedicle of nude mice. Reconstruction of 3500 histological serial
      sections demonstrated that a new vascular network composed of venous-venous loops
      of varying sizes grows inside the tumor from the wall of the adjacent main vein.
      Loops elongate and remodel to establish complex loop systems. The mechanisms of
      loop formation and remodeling correspond to intussusceptive microvascular growth
      (IMG). In the tissue surrounding the tumor segmentation, another mechanism of IMG
      is prevalent in venous vessels. Comparison to vascular morphogenesis in the
      ovariectomized pedicle not only confirms the existence of corresponding
      mechanisms in both systems, but also reveals numerous sprouts that are
      superimposed onto loop systems and pathological deviations of loop formation,
      remodeling, and segmentation in the tumor. These pathological mechanisms
      interfere with vessel patency that likely cause heterogenous perfusion and
      hypoxia thus perpetuating angiogenesis. Blood vessel formation based on IMG was
      also detected in a large thrombus that completely occluded a part of an ovarian
      artery branch.

PMID- 11597998
TI  - Crystal structures of NK1-heparin complexes reveal the basis for NK1 activity and
      enable engineering of potent agonists of the MET receptor.
AB  - NK1 is a splice variant of the polypeptide growth factor HGF/SF, which consists
      of the N-terminal (N) and first kringle (K) domain and requires heparan sulfate
      or soluble heparin for activity. We describe two X-ray crystal structures of NK1
      heparin complexes that define a heparin-binding site in the N domain, in which a
      major role is played by R73, with further contributions from main chain atoms of
      T61, K63 and G79 and the side chains of K60, T61, R76, K62 and K58. Mutagenesis
      experiments demonstrate that heparin binding to this site is essential for
      dimerization in solution and biological activity of NK1. Heparin also comes into
      contact with a patch of positively charged residues (K132, R134, K170 and R181)
      in the K domain. Mutation of these residues yields NK1 variants with increased
      biological activity. Thus, we uncover a complex role for heparan sulfate in which
      binding to the primary site in the N domain is essential for biological activity
      whereas binding to the K domain reduces activity. We exploit the interaction
      between heparin and the K domain site in order to engineer NK1 as a potent
      receptor agonist and suggest that dual (positive and negative) control may be a
      general mechanism of heparan sulfate-dependent regulation of growth factor
      activity.

PMID- 11597999
TI  - Calcium-dependent protein kinases play an essential role in a plant defence
      response.
AB  - Calcium-dependent protein kinases (CDPKs) comprise a large family of
      serine/threonine kinases in plants and protozoans. We isolated two related CDPK
      cDNAs (NtCDPK2 and NtCDPK3) from Nicotiana tabacum. These CDPK transcripts are
      elevated after race-specific defence elicitation and hypo-osmotic stress.
      Transiently expressed myc-epitope-tagged NtCDPK2 in Nicotiana benthamiana and
      N.tabacum leaves showed a rapid transient interconversion to an activated form
      after elicitation and hypo-osmotic stress. The Avr9 race-specific elicitor caused
      a more pronounced and sustained response. This transition is due to
      phosphorylation of the CDPK. Immuno complex kinase assays with epitope-tagged
      NtCDPK2 showed that stress-induced phosphorylation and interconversion of NtCDPK2
      correlates with an increase in enzymatic activity. The function of NtCDPK2 in
      plant defence was investigated by employing virus-induced gene silencing (VIGS)
      in N.benthamiana. CDPK-silenced plants showed a reduced and delayed
      hypersensitive response after race-specific elicitation in a gene-for-gene
      interaction, and lacked an accompanying wilting phenotype. Silencing correlated
      with loss of CDPK mRNA, whereas mRNA accumulation of mitogen-activated protein
      kinase WIPK remained unaltered.

PMID- 11598000
TI  - The helical domain of GBP-1 mediates the inhibition of endothelial cell
      proliferation by inflammatory cytokines.
AB  - Inflammatory cytokines (IC) activate endothelial cell adhesiveness for monocytes
      and inhibit endothelial cell growth. Here we report the identification of the
      human guanylate binding protein-1 (GBP-1) as the key and specific mediator of the
      anti-proliferative effect of IC on endothelial cells. GBP-1 expression was
      induced by IC, downregulated by angiogenic growth factors, and inversely related
      to cell proliferation both in vitro in microvascular and macrovascular
      endothelial cells and in vivo in vessel endothelial cells of Kaposi's sarcoma.
      Experimental modulation of GBP-1 expression demonstrated that GBP-1 mediates
      selectively the anti-proliferative effect of IC, without affecting endothelial
      cell adhesiveness for monocytes. GBP-1 anti-proliferative activity did not affect
      ERK-1/2 activation, occurred in the absence of apoptosis, was found to be
      independent of the GTPase activity and isoprenylation of the molecule, but was
      specifically mediated by the C-terminal helical domain of the protein. These
      results define GBP-1 as an important tool for dissection of the complex activity
      of IC on endothelial cells, and detection and specific modulation of the IC
      activated non-proliferating phenotype of endothelial cells in vascular diseases.

PMID- 11598001
TI  - Link of the unique oncogenic properties of adenovirus type 9 E4-ORF1 to a select
      interaction with the candidate tumor suppressor protein ZO-2.
AB  - Adenovirus type 9 (Ad9) is distinct among human adenoviruses because it elicits
      solely mammary tumors in animals and its primary oncogenic determinant is the E4
      region-encoded ORF1 (E4-ORF1) protein. We report here that the PDZ domain
      containing protein ZO-2, which is a candidate tumor suppressor protein, is a
      cellular target for tumorigenic Ad9 E4-ORF1 but not for non-tumorigenic wild-type
      E4-ORF1 proteins encoded by adenovirus types 5 and 12. Complex formation was
      mediated by the C-terminal PDZ domain-binding motif of Ad9 E4- ORF1 and the first
      PDZ domain of ZO-2, and in cells this interaction resulted in aberrant
      sequestration of ZO-2 within the cytoplasm. Furthermore, transformation-defective
      Ad9 E4-ORF1 mutants exhibited impaired binding to and sequestration of ZO-2 in
      cells, and overexpression of wild-type ZO-2, but not mutant ZO-2 lacking the
      second and third PDZ domains, interfered with Ad9 E4-ORF1-induced focus
      formation. Our results suggest that the select capacity to complex with the
      candidate tumor suppressor protein ZO-2 is key to defining the unique
      transforming and tumorigenic properties of the Ad9 E4-ORF1 oncoprotein.

PMID- 11598002
TI  - Oxidative stress inhibits the repair of photodamage to the photosynthetic
      machinery.
AB  - Absorption of excess light energy by the photosynthetic machinery results in the
      generation of reactive oxygen species (ROS), such as H2O2. We investigated the
      effects in vivo of ROS to clarify the nature of the damage caused by such excess
      light energy to the photosynthetic machinery in the cyanobacterium Synechocystis
      sp. PCC 6803. Treatments of cyanobacterial cells that supposedly increased
      intracellular concentrations of ROS apparently stimulated the photodamage to
      photosystem II by inhibiting the repair of the damage to photosystem II and not
      by accelerating the photodamage directly. This conclusion was confirmed by the
      effects of the mutation of genes for H2O2-scavenging enzymes on the recovery of
      photosystem II. Pulse labeling experiments revealed that ROS inhibited the
      synthesis of proteins de novo. In particular, ROS inhibited synthesis of the D1
      protein, a component of the reaction center of photosystem II. Northern and
      western blot analyses suggested that ROS might influence the outcome of
      photodamage primarily via inhibition of translation of the psbA gene, which
      encodes the precursor to D1 protein.

PMID- 11598003
TI  - Exploration of the pore structure of a peptide-gated Na+ channel.
AB  - The FMRF-amide-activated sodium channel (FaNaC), a member of the ENaC/Degenerin
      family, is a homotetramer, each subunit containing two transmembrane segments. We
      changed independently every residue of the first transmembrane segment (TM1) into
      a cysteine and tested each position's accessibility to the cysteine covalent
      reagents MTSET and MTSES. Eleven mutants were accessible to the cationic MTSET,
      showing that TM1 faces the ion translocation pathway. This was confirmed by the
      accessibility of cysteines present in the acid-sensing ion channels and other
      mutations introduced in FaNaC TM1. Modification of accessibilities for positions
      69, 71 and 72 in the open state shows that the gating mechanism consists of the
      opening of a constriction close to the intracellular side. The anionic MTSES did
      not penetrate into the channel, indicating the presence of a charge selectivity
      filter in the outer vestibule. Furthermore, amiloride inhibition resulted in the
      channel occlusion in the middle of the pore. Summarizing, the ionic pore of FaNaC
      includes a large aqueous cavity, with a charge selectivity filter in the outer
      vestibule and the gate close to the interior.

PMID- 11598004
TI  - A WASp-VASP complex regulates actin polymerization at the plasma membrane.
AB  - Proteins of the Wiskott-Aldrich syndrome and Ena/VASP families both play
      essential functions in the regulation of actin dynamics at the cell leading edge.
      However, possibilities of functional interplay between members of these two
      families have not been addressed. Here we show that, in hemopoietic cells,
      recruitment of the C-terminal VCA (Verprolin homology, Cofilin homology, Acidic)
      domain of WASp at the plasma membrane by a ligand technique using rapamycin as an
      intermediate is not sufficient to elicit efficient Arp2/3 complex-mediated actin
      polymerization. Other domains of WASp, in particular the proline-rich domain, are
      required for the formation of actin-rich structures. An in vitro analysis
      demonstrates that the proline-rich domain of WASp binds VASP with an affinity of
      approximately 10(6) M(-1). In addition, WASp and VASP both accumulate in actin
      rich phagocytic cups. Finally, in a reconstituted motility medium, VASP enhances
      actin-based propulsion of WASp-coated beads in a fashion reminiscent of its
      effect on Listeria movement. We propose that VASP and WASp cooperation is
      essential in stimulating actin assembly and membrane protrusion at the leading
      edge.

PMID- 11598005
TI  - Repacking of the transmembrane domains of P-glycoprotein during the transport
      ATPase cycle.
AB  - P-glycoprotein (P-gp) is an ABC (ATP-binding cassette) transporter, which
      hydrolyses ATP and extrudes cytotoxic drugs from mammalian cells. P-gp consists
      of two transmembrane domains (TMDs) that span the membrane multiple times, and
      two cytoplasmic nucleotide-binding domains (NBDs). We have determined projection
      structures of P-gp trapped at different steps of the transport cycle and
      correlated these structures with function. In the absence of nucleotide, an
      approximately 10 A resolution structure was determined by electron cryo
      microscopy of two-dimensional crystals. The TMDs form a chamber within the
      membrane that appears to be open to the extracellular milieu, and may also be
      accessible from the lipid phase at the interfaces between the two TMDs.
      Nucleotide binding causes a repacking of the TMDs and reduction in drug binding
      affinity. Thus, ATP binding, not hydrolysis, drives the major conformational
      change associated with solute translocation. A third distinct conformation of the
      protein was observed in the post-hydrolytic transition state prior to release of
      ADP/P(i). Biochemical data suggest that these rearrangements may involve rotation
      of transmembrane alpha-helices. A mechanism for transport is suggested.

PMID- 11598006
TI  - Apocytochrome c requires the TOM complex for translocation across the
      mitochondrial outer membrane.
AB  - The import of proteins into the mitochondrial intermembrane space differs in
      various aspects from the classical import pathway into the matrix. Apocytochrome
      c defines one of several pathways known to reach the intermembrane space, yet the
      components and pathways involved in outer membrane translocation are poorly
      defined. Here, we report the reconstitution of the apocytochrome c import
      reaction using proteoliposomes harbouring purified components. Import
      specifically requires the protease-resistant part of the TOM complex and is
      driven by interactions of the apoprotein with internal parts of the complex
      (involving Tom40) and the 'trans-side receptor' cytochrome c haem lyase. Despite
      the necessity of TOM complex function, the translocation pathway of apocytochrome
      c does not overlap with that of presequence-containing preproteins. We conclude
      that the TOM complex is a universal preprotein translocase that mediates membrane
      passage of apocytochrome c and other preproteins along distinct pathways.
      Apocytochrome c may provide a paradigm for the import of other small proteins
      into the intermembrane space such as factors used in apoptosis and protection
      from stress.

PMID- 11598007
TI  - Trafficking and assembly of the cytoadherence complex in Plasmodium falciparum
      infected human erythrocytes.
AB  - After invading human erythrocytes, the malarial parasite Plasmodium falciparum,
      initiates a remarkable process of secreting proteins into the surrounding
      erythrocyte cytoplasm and plasma membrane. One of these exported proteins, the
      knob-associated histidine-rich protein (KAHRP), is essential for microvascular
      sequestration, a strategy whereby infected red cells adhere via knob structures
      to capillary walls and thus avoid being eliminated by the spleen. This
      cytoadherence is an important factor in many of the deaths caused by malaria.
      Green fluorescent protein fusions and fluorescence recovery after photobleaching
      were used to follow the pathway of KAHRP deployment from the parasite
      endomembrane system into an intermediate depot between parasite and host, then
      onwards to the erythrocyte cytoplasm and eventually into knobs. Sequence elements
      essential to individual steps in the pathway are defined and we show that
      parasite-derived structures, known as Maurer's clefts, are an elaboration of the
      canonical secretory pathway that is transposed outside the parasite into the host
      cell, the first example of its kind in eukaryotic biology.

PMID- 11598008
TI  - Rho1p and Cdc42p act after Ypt7p to regulate vacuole docking.
AB  - Rho GTPases, which control polarized cell growth through cytoskeletal
      reorganization, have recently been implicated in the control of endo- and
      exocytosis. We now report that both Rho1p and Cdc42p have a direct role in
      mediating the docking stage of homotypic vacuole fusion. Vacuoles prepared from
      strains with temperature-sensitive alleles of either Rho1p or Cdc42p are
      thermolabile for fusion. RhoGDI (Rdi1p), which extracts Rho1p and Cdc42p from the
      vacuole membrane, blocks vacuole fusion. The Rho GTPases can not fulfill their
      function as long as priming and Ypt7p-dependent tethering are inhibited. However,
      reactions that are reversibly blocked after docking by the calcium chelator BAPTA
      have passed the point of sensitivity to Rdi1p. Extraction and removal of Ypt7p,
      Rho1p and Cdc42p from docked vacuoles (by Gdi1p, Gyp7p and Rdi1p) does not impede
      subsequent membrane fusion, which is still sensitive to GTPgammaS. Thus, multiple
      GTPases act in a defined sequence to regulate the docking steps of vacuole
      fusion.

PMID- 11598009
TI  - Cdc42p functions at the docking stage of yeast vacuole membrane fusion.
AB  - Membrane fusion reactions have been considered to be primarily regulated by Rab
      GTPases. In the model system of homotypic vacuole fusion in the yeast
      Saccharomyces cerevisiae, we show that Cdc42p, a member of the Rho family of
      GTPases, has a direct role in membrane fusion. Genetic evidence suggested a
      relationship between Cdc42p and Vtc1p/Nrf1p, a central part of the vacuolar
      membrane fusion machinery. Vacuoles from cdc42 temperature-sensitive mutants are
      deficient for fusion at the restrictive temperature. Specific amino acid changes
      on the Cdc42p protein surface in these mutants define the putative interaction
      domain that is crucial for its function in membrane fusion. Affinity-purified
      antibodies to this domain inhibited the in vitro fusion reaction. Using these
      antibodies in kinetic analyses and assays for subreactions of the priming,
      docking and post-docking phase of the reaction, we show that Cdc42p action
      follows Ypt7p-dependent tethering, but precedes the formation of trans-SNARE
      complexes. Thus, our data define an effector binding domain of Cdc42p by which it
      regulates the docking reaction of vacuole fusion.

PMID- 11598010
TI  - Src transduces erythropoietin-induced differentiation signals through
      phosphatidylinositol 3-kinase.
AB  - In this study, we examined the molecular mechanism of erythropoietin-initiated
      signal transduction of erythroid differentiation through Src and
      phosphatidylinositol 3-kinase (PI3-kinase). Antisense oligonucleotides against
      src but not lyn inhibited the formation of erythropoietin-dependent colonies
      derived from human bone marrow cells and erythropoietin-induced differentiation
      of K562 human erythroleukaemia cells. Antisense p85alpha oligonucleotide or
      LY294002, a selective inhibitor of PI3-kinase, independently inhibited the
      formation of erythropoietin-dependent colonies. In K562 cells, Src associated
      with PI3-kinase in response to erythropoietin. Antisense src RNA expression in
      K562 cells inhibited the erythropoietin-induced activation of PI3-kinase and its
      association with erythropoietin receptor. PP1, a selective inhibitor of the Src
      family, reduced erythropoietin-induced tyrosine phosphorylation of erythropoietin
      receptor and its association with PI3-kinase in F-36P human erythroleukaemia
      cells. The coexpression experiments and in vitro kinase assay further
      demonstrated that Src directly tyrosine-phosphorylated erythropoietin receptor,
      and associated with PI3-kinase. In vitro binding experiments proved that
      glutathione S-transferase-p85alpha N- or C-terminal SH2 domains independently
      bound to erythropoietin receptor, which was tyrosine-phosphorylated by Src. Taken
      together, Src transduces the erythropoietin-induced erythroid differentiation
      signals by regulating PI3-kinase activity.

PMID- 11598011
TI  - TRAF6 is a critical mediator of signal transduction by the viral oncogene latent
      membrane protein 1.
AB  - The oncogenic latent membrane protein 1 (LMP1) of the Epstein-Barr virus recruits
      tumor necrosis factor-receptor (TNFR)-associated factors (TRAFs), the TNFR
      associated death domain protein (TRADD) and JAK3 to induce intracellular
      signaling pathways. LMP1 serves as the prototype of a TRADD-binding receptor that
      transforms cells but does not induce apoptosis. Here we show that TRAF6
      critically mediates LMP1 signaling to p38 mitogen-activated protein kinase (MAPK)
      via a MAPK kinase 6-dependent pathway. In addition, NF-kappaB but not c-Jun N
      terminal kinase 1 (JNK1) induction by LMP1 involves TRAF6. The PxQxT motif of the
      LMP1 C-terminal activator region 1 (CTAR1) and tyrosine 384 of CTAR2 together are
      essential for full p38 MAPK activation and for TRAF6 recruitment to the LMP1
      signaling complex. Dominant-negative TRADD blocks p38 MAPK activation by LMP1.
      The data suggest that entry of TRAF6 into the LMP1 complex is mediated by TRADD
      and TRAF2. In TRAF6-knockout fibroblasts, significant induction of p38 MAPK by
      LMP1 is dependent on the ectopic expression of TRAF6. We describe a novel role of
      TRAF6 as an essential signaling mediator of a transforming oncogene, downstream
      of TRADD and TRAF2.

PMID- 11598012
TI  - PKCbeta modulates antigen receptor signaling via regulation of Btk membrane
      localization.
AB  - Mutations in Bruton's tyrosine kinase (Btk) result in X-linked agammaglobulinemia
      (XLA) in humans and X-linked immunodeficiency (xid) in mice. While targeted
      disruption of the protein kinase C-beta (PKCbeta) gene in mice results in an
      immunodeficiency similar to xid, the overall tyrosine phosphorylation of Btk is
      significantly enhanced in PKCbeta-deficient B cells. We provide direct evidence
      that PKCbeta acts as a feedback loop inhibitor of Btk activation. Inhibition of
      PKCbeta results in a dramatic increase in B-cell receptor (BCR)-mediated Ca2+
      signaling. We identified a highly conserved PKCbeta serine phosphorylation site
      in a short linker within the Tec homology domain of Btk. Mutation of this
      phosphorylation site led to enhanced tyrosine phosphorylation and membrane
      association of Btk, and augmented BCR and FcepsilonRI-mediated signaling in B and
      mast cells, respectively. These findings provide a novel mechanism whereby
      reversible translocation of Btk/Tec kinases regulates the threshold for
      immunoreceptor signaling and thereby modulates lymphocyte activation.

PMID- 11598013
TI  - The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear
      pore complex anchoring and import of a subset of nuclear proteins.
AB  - The nuclear pore complex (NPC) is a large proteinaceous structure through which
      bidirectional transport of macromolecules across the nuclear envelope (NE) takes
      place. Nup153 is a peripheral NPC component that has been implicated in protein
      and RNP transport and in the interaction of NPCs with the nuclear lamina. Here,
      Nup153 is localized by immunogold electron microscopy to a position on the
      nuclear ring of the NPC. Nuclear reconstitution is used to investigate the role
      of Nup153 in nucleo- cytoplasmic transport and NPC architecture. NPCs assembled
      in the absence of Nup153 lacked several nuclear basket components, were unevenly
      distributed in the NE and, unlike wild-type NPCs, were mobile within the NE.
      Importin alpha/beta-mediated protein import into the nucleus was strongly reduced
      in the absence of Nup153, while transportin-mediated import was unaffected. This
      was due to a reduction in import complex translocation rather than to defective
      receptor recycling. Our results therefore reveal functions for Nup153 in NPC
      assembly, in anchoring NPCs within the NE and in mediating specific nuclear
      import events.

PMID- 11598014
TI  - Tuning pacemaker frequency of individual dopaminergic neurons by Kv4.3L and
      KChip3.1 transcription.
AB  - The activity of dopaminergic (DA) substantia nigra (SN) neurons is essential for
      voluntary movement control. An intrinsic pacemaker in DA SN neurons generates
      their tonic spontaneous activity, which triggers dopamine release. We show here,
      by combining multiplex and quantitative real-time single-cell RT- PCR with slice
      patch-clamp electrophysiology, that an A-type potassium channel mediated by Kv4.3
      and KChip3 subunits has a key role in pacemaker control. The number of active A
      type potassium channels is not only tightly associated with the pacemaker
      frequency of individual DA SN neurons, but is also highly correlated with their
      number of Kv4.3L (long splice variant) and KChip3.1 (long splice variant) mRNA
      molecules. Consequently, the variation of Kv4alpha and Kv4beta subunit transcript
      numbers is sufficient to explain the full spectrum of spontaneous pacemaker
      frequencies in identified DA SN neurons. This linear coupling between Kv4alpha as
      well as Kv4beta mRNA abundance, A-type channel density and pacemaker frequency
      suggests a surprisingly simple molecular mechanism for how DA SN neurons tune
      their variable firing rates by transcriptional control of ion channel genes.

PMID- 11598015
TI  - Brinker requires two corepressors for maximal and versatile repression in Dpp
      signalling.
AB  - decapentaplegic (dpp) encodes a Drosophila transforming growth factor-beta
      homologue that functions as a morphogen in the developing embryo and in adult
      appendage formation. In the wing imaginal disc, a Dpp gradient governs patterning
      along the anteroposterior axis by inducing regional expression of diverse genes
      in a concentration-dependent manner. Recent studies show that responses to graded
      Dpp activity also require an input from a complementary and opposing gradient of
      Brinker (Brk), a transcriptional repressor protein encoded by a Dpp target gene.
      Here we show that Brk harbours a functional and transferable repression domain,
      through which it recruits the corepressors Groucho and CtBP. By analysing
      transcriptional outcomes arising from the genetic removal of these corepressors,
      and by ectopically expressing Brk variants in the embryo, we demonstrate that
      these corepressors are alternatively used by Brk for repressing some Dpp
      responsive genes, whereas for repressing other distinct target genes they are not
      required. Our results show that Brk utilizes multiple means to repress its
      endogenous target genes, allowing repression of a multitude of complex Dpp target
      promoters.

PMID- 11598016
TI  - Cyclin A-CDK phosphorylates Sp1 and enhances Sp1-mediated transcription.
AB  - Cyclin A-mediated activation of cyclin-dependent kinases (CDKs) is essential for
      cell cycle transversal. Cyclin A activity is regulated on several levels and
      cyclin A elevation in a number of cancers suggests a role in tumorigenesis. In
      the present study, we used a modified DNA binding site selection and PCR
      amplification procedure to identify DNA binding proteins that are potential
      substrates of cyclin A-CDK. One of the sequences identified is the Sp1
      transcription factor binding site. Co-immunoprecipitation experiments show that
      cyclin A and Sp1 can interact physically. In vitro and in vivo phosphorylation
      studies indicate that cyclin A-CDK complexes can phosphorylate Sp1. The
      phosphorylation site is located in the N-terminal region of the protein. Cells
      overexpressing cyclin A have elevated levels of Sp1 DNA binding activity,
      suggesting that cyclin A-CDK-mediated phosphorylation augments Sp1 DNA binding
      properties. In co-transfection studies, cyclin A expression stimulated
      transcription from an Sp1-regulated promoter. Mutation of the phosphorylation
      site abrogated cyclin A-CDK-dependent phosphorylation, augmentation of Sp1
      transactivation function and DNA binding activity.

PMID- 11598017
TI  - The hnRNP A1 protein regulates HIV-1 tat splicing via a novel intron silencer
      element.
AB  - The generation of >30 different HIV-1 mRNAs is achieved by alternative splicing
      of one primary transcript. The removal of the second tat intron is regulated by a
      combination of a suboptimal 3' splice site and cis-acting splicing enhancers and
      silencers. Here we show that hnRNP A1 inhibits splicing of this intron via a
      novel heterogeneous nuclear ribonucleoprotein (hnRNP) A1-responsive intron
      splicing silencer (ISS) that can function independently of the previously
      characterized exon splicing silencer (ESS3). Surprisingly, depletion of hnRNP A1
      from the nuclear extract (NE) enables splicing to proceed in NE that contains 100
      fold reduced concentrations of U2AF and normal levels of SR proteins, conditions
      that do not support processing of other efficiently spliced pre-mRNAs.
      Reconstituting the extract with recombinant hnRNP A1 protein restores splicing
      inhibition at a step subsequent to U2AF binding, mainly at the time of U2 snRNP
      association. hnRNP A1 interacts specifically with the ISS sequence, which
      overlaps with one of three alternative branch point sequences, pointing to a
      model where the entry of U2 snRNP is physically blocked by hnRNP A1 binding.

PMID- 11598018
TI  - Antagonistic effects of T-Ag and VP16 reveal a role for RNA pol II elongation on
      alternative splicing.
AB  - Here we investigate the promoter control of alternative splicing by studying two
      transcriptional activators on templates under replicating conditions. SV40 large
      T-antigen (T-Ag) activates template replication only 2-fold but transcription 25
      fold. T-Ag-mediated replication, reported to inhibit RNA polymerase II
      elongation, provokes a 10- to 30-fold increase in the inclusion of the
      fibronectin EDI exon into mature mRNA. The T-Ag effect is exon specific, occurs
      in cis and depends strictly on DNA replication and not on cell transformation.
      VP16, an activator of transcriptional initiation and elongation, has a similar
      effect on transcription but the opposite effect on splicing: EDI inclusion is
      inhibited by 35-fold. VP16 completely reverts the T-Ag effect, but a VP16 mutant
      with reduced elongation ability provokes only partial reversion. Both T-Ag and
      VP16 promote conspicuous co-localization of mRNA with nuclear speckles that
      contain the SR protein SF2/ASF, a positive regulator of EDI inclusion. Therefore,
      we conclude that co-localization of transcripts and speckles is not sufficient to
      stimulate EDI inclusion.

PMID- 11598019
TI  - Herpes simplex virus ICP27 protein provides viral mRNAs with access to the
      cellular mRNA export pathway.
AB  - The role of herpes simplex virus ICP27 protein in mRNA export is investigated by
      microinjection into Xenopus laevis oocytes. ICP27 dramatically stimulates the
      export of intronless viral mRNAs, but has no effect on the export of cellular
      mRNAs, U snRNAs or tRNA. Use of inhibitors shows, in contrast to previous
      suggestions, that ICP27 neither shuttles nor exports viral mRNA via the CRM1
      pathway. Instead, ICP27-mediated viral RNA export requires REF and TAP/NXF1,
      factors involved in cellular mRNA export. ICP27 binds directly to REF and
      complexes containing ICP27, REF and TAP are found in vitro and in virally
      infected cells. A mutant ICP27 that does not interact with REF is inactive in
      viral mRNA export. We propose that ICP27 associates with viral mRNAs and recruits
      TAP/NXF1 via its interaction with REF proteins, allowing the otherwise
      inefficiently exported viral mRNAs to access the TAP-mediated export pathway.
      This represents a novel mechanism for export of viral mRNAs.

PMID- 11598020
TI  - Establishment and maintenance of sister chromatid cohesion in fission yeast by a
      unique mechanism.
AB  - During S phase, chromatid cohesion is established only between nascent sisters
      and with faithful pairing along their entire region, but how this is ensured is
      unknown. Here we report that sister chromatid cohesion is formed and maintained
      by a unique mechanism. In fission yeast, Eso1p, functioning in close coupling to
      DNA replication, establishes sister chromatid cohesion whereas the newly
      identified Cohesin-associated protein Pds5p hinders the establishment of cohesion
      until counteracted by Eso1p, yet stabilizes cohesion once it is established.
      Eso1p interacts physically with Pds5p via its Ctf7p/Eco1p-homologous domain.

PMID- 11598021
TI  - Werner syndrome protein interacts with human flap endonuclease 1 and stimulates
      its cleavage activity.
AB  - Werner syndrome (WS) is a human premature aging disorder characterized by
      chromosomal instability. The cellular defects of WS presumably reflect
      compromised or aberrant function of a DNA metabolic pathway that under normal
      circumstances confers stability to the genome. We report a novel interaction of
      the WRN gene product with the human 5' flap endonuclease/5'-3' exonuclease (FEN
      1), a DNA structure-specific nuclease implicated in DNA replication,
      recombination and repair. WS protein (WRN) dramatically stimulates the rate of
      FEN-1 cleavage of a 5' flap DNA substrate. The WRN-FEN-1 functional interaction
      is independent of WRN catalytic function and mediated by a 144 amino acid domain
      of WRN that shares homology with RecQ DNA helicases. A physical interaction
      between WRN and FEN-1 is demonstrated by their co-immunoprecipitation from HeLa
      cell lysate and affinity pull-down experiments using a recombinant C-terminal
      fragment of WRN. The underlying defect of WS is discussed in light of the
      evidence for the interaction between WRN and FEN-1.

PMID- 11598022
TI  - Transient promoter formation: a new feedback mechanism for regulation of IS911
      transposition.
AB  - IS911 transposition involves a free circular transposon intermediate where the
      terminal inverted repeat sequences are connected. Transposase synthesis is
      usually driven by a weak promoter, p(IRL), in the left end (IRL). Circle junction
      formation creates a strong promoter, p(junc), with a -35 sequence located in the
      right end and the -10 sequence in the left. p(junc) assembly would permit an
      increase in synthesis of transposase from the transposon circle, which would be
      expected to stimulate integration. Insertion results in p(junc) disassembly and a
      return to the low p(IRL)- driven transposase levels. We demonstrate that p(junc)
      plays an important role in regulating IS911 transposition. Inactivation of
      p(junc) strongly decreased IS911 transposition when transposase was produced in
      its natural configuration. This novel feedback mechanism permits transient and
      controlled activation of integration only in the presence of the correct
      (circular) intermediate. We have also investigated other members of the IS3 and
      other IS families. Several, but not all, IS3 family members possess p(junc)
      equivalents, underlining that the regulatory mechanisms adopted to fine-tune
      transposition may be different.

PMID- 11598023
TI  - Lactate stimulation of gonococcal metabolism in media containing glucose:
      mechanism, impact on pathogenicity, and wider implications for other pathogens.

PMID- 11598024
TI  - Enteropathogenic Escherichia coli virulence factor bundle-forming pilus has a
      binding specificity for phosphatidylethanolamine.
AB  - The bundle-forming pilus (BFP) of enteropathogenic Escherichia coli (EPEC), an
      established virulence factor encoded on the EPEC adherence factor (EAF) plasmid,
      has been implicated in the formation of bacterial autoaggregates and in the
      localized adherence of EPEC to cultured epithelial cells. While understanding of
      the pathogenic mechanism of this organism is rapidly improving, a receptor ligand
      for BFP has not yet been identified. We now report, using both solid-phase and
      liposome binding assays, that BFP expression correlates with
      phosphatidylethanolamine (PE) binding. In a thin-layer chromatogram overlay
      assay, specific recognition of PE was documented for BFP-expressing strains,
      including E2348/69, a wild-type EPEC clinical isolate, as well as a laboratory
      strain, HB101, transformed with a bfp-carrying plasmid. Strains which did not
      express BFP did not bind PE, including a bfpA disruptional mutant of E2348/69,
      EAF plasmid-cured E2348/69, and HB101. E2348/69 also aggregated PE-containing
      liposomes but not phosphatidylcholine- or phosphatidylserine-containing
      liposomes, while BFP-negative strains did not produce aggregates with any tested
      liposomes. Purified BFP preparations bound commercial PE standards as well as a
      PE-containing band within lipid extracts from human epithelial cells and from
      E2348/69. Our results therefore indicate a specific interaction between BFP and
      PE and suggest that PE may serve as a BFP receptor for bacterial autoaggregation
      and may promote localized adherence to host cells, both of which contribute to
      bacterial pathogenesis.

PMID- 11598025
TI  - Enhancement of Mycobacterium tuberculosis-induced tumor necrosis factor alpha
      production from primary human monocytes by an activated T-cell membrane-mediated
      mechanism.
AB  - Mycobacterium tuberculosis alone induces small, donor-variable amounts of tumor
      necrosis factor alpha (TNF-alpha) from primary human monocytes in vitro. However,
      TNF-alpha release is increased 5- to 500-fold when fixed activated T cells (FAT)
      or their isolated, unfixed membranes are added to this system. This FAT-induced
      synergy was at least as potent as that induced by gamma interferon (IFN-gamma) at
      100 U/ml. FAT-enhanced TNF-alpha production is at least in part transcriptionally
      mediated, as reflected by quantitative changes in TNF-alpha mRNA between 2 and 6
      h poststimulation. Unlike IFN-gamma-cocultured cells, FAT-treated monocytes
      appeared not to have enhanced TNF-alpha message stability, suggesting that de
      novo transcription may be involved in this effect. Furthermore, M. tuberculosis
      alone induced only minimal DNA binding of monocyte NF-kappaB, but cells treated
      with M. tuberculosis and FAT potentiated NF-kappaB activity more effectively. It
      is therefore possible that one mechanism by which FAT synergize with M.
      tuberculosis to stimulate TNF-alpha production is via NF-kappaB-enhanced
      transcription. These data strongly suggest that in the interaction of cells
      involved in the immune response to M. tuberculosis, T-cell stimulation of
      monocyte TNF-alpha production involves a surface membrane interaction(s) as well
      as soluble mediators.

PMID- 11598026
TI  - Dual role of the Leishmania major ribosomal protein S3a homologue in regulation
      of T- and B-cell activation.
AB  - We have recently characterized a novel Leishmania major gene encoding a
      polypeptide of 30 kDa that was homologous to mammalian ribosomal protein S3a and
      was named LmS3a-related protein (LmS3arp). The protein was found to be expressed
      by all the Leishmania species so far examined (L. infantum, L. amazonensis, and
      L. mexicana). In the present study we have extended our approach to the analysis
      of LmS3arp activity on T- and B-cell functions in a murine model. The results
      presented in this report show that LmS3arp plays a dual role in the regulation of
      T- and B-cell reactivity. Indeed, we found that injection of the LmS3arp
      recombinant protein (rLmS3arp) into BALB/c mice induces preferential activation
      of B cells, as shown by the following criteria: (i) increased expression of CD69
      molecules on immunoglobulin M (IgM)-secreting spleen cells, (ii) a considerable
      increase of IgM-secreting B cells, and (iii) elevated levels of IgM antibodies in
      the sera of injected animals. Moreover, the IgM antibodies are not specific to
      the Leishmania antigens but preferentially recognize heterologous antigens like
      myosin, thyroglobulin, DNA, and keyhole limpet hemocyanin. Furthermore, the
      strong polyclonal expansion of nonspecific, non-parasite-directed B-cell clones
      induced by rLmS3arp is concomitant with a marked inhibition of T-cell
      proliferation. Analysis of cytokine production revealed a significant
      downregulation of gamma interferon, interleukin-2 (IL-2), and IL-12 secretion.
      Taken together, our data suggest that rLmS3arp, through direct or indirect action
      toward B and T cells and cytokine secretion, could participate in the
      immunoregulatory processes that play a role in the balance of the Th1 and Th2
      immune response.

PMID- 11598027
TI  - Identification of an antigenic epitope in Helicobacter pylori urease that induces
      neutralizing antibody production.
AB  - We previously reported a mouse monoclonal antibody (MAb), termed L2, specific for
      Helicobacter pylori urease strongly inhibited its enzymatic activity. Here, to
      gain insight into how this antibody affects urease activity, the epitope that was
      recognized by the antibody was determined. By screening a panel of overlapping
      synthetic peptides covering the entire sequence of the two subunits (UreA and
      UreB), we identified a stretch of UreB-derived 19 amino acid (aa) residues (UB
      33; aa 321 to 339, CHHLDKSIKEDVQFADSRI) that was specifically recognized by the
      L2 antibody. Further sequential amino acid deletion of the 19-mer peptide from
      either end allowed us to determine the minimal epitope as 8 amino acid residues
      (F8; SIKEDVQF) for L2 reactivity. This epitope appears to lie exactly on a short
      sequence which formed a flap over the active site of urease, suggesting that
      binding of the L2 antibody sterically inhibits access of urea, the substrate of
      urease. Finally, immunization of rabbits with either the 19-mer peptide or the 8
      mer minimal epitope resulted in generation of antiurease antibodies that were
      capable of inhibiting the enzymatic activity. Since urease is critical for
      virulence of H. pylori, antigenic peptides that induce production of antibodies
      to inhibit its enzymatic activity may potentially be a useful tool as a vaccine
      for prevention and treatment of H. pylori infection.

PMID- 11598028
TI  - Effect of attenuated Salmonella enterica serovar Typhimurium expressing a
      Streptococcus mutans antigen on secondary responses to the cloned protein.
AB  - Attenuated Salmonella enterica serovar Typhimurium has been used for targeted
      delivery of recombinant antigens to gut- and nose-associated lymphoid tissues.
      Contradictory reports have described the effect of preexisting immunity to the
      antigen delivery vehicle. We decided to examine this discrepancy by studying the
      effect of immunizing mice by the intranasal (i.n.) route with Salmonella
      expressing an insoluble protein and to study the ability to augment recall
      responses by boosting with either Salmonella-expressed protein or purified
      soluble protein alone. The glucan-binding domain (GLU) of the enzyme
      glucosyltransferase (GTF), which is an important virulence factor of
      Streptococcus mutans, was recombinantly expressed in the insoluble phase in S.
      enterica serovar Typhimurium, and the immunogenicity of this construct was
      studied in mice. We examined the induction of primary immune responses by
      insoluble GLU polypeptide delivered in Salmonella at week 1 (groups 1 and 2) and
      recall responses after a week 15 boost with either Salmonella expressing GLU
      (group 1) or purified GLU polypeptide (groups 2 and 3). Group 4 served as the
      control and received phosphate-buffered saline alone by the i.n. route.
      Significant anti-GLU serum immunoglobulin G (IgG) levels were seen in groups 1,
      2, and 3 at week 18 (P < 0.001), i.e., 3 weeks after the booster immunization.
      Mice in group 2, who received Salmonella followed by GLU, had the highest GLU
      specific IgG levels among all groups. The serum IgG levels persisted in all
      responding groups for at least 7 weeks after the boost (week 22). The IgG2a/IgG1
      subclass ratio of serum anti-GLU antibodies in group 1 significantly increased
      after the boost. These results support the induction of a type 1-like immune
      response to GLU after primary and booster immunizations with Salmonella
      expressing GLU. On the other hand, group 2 mice, which received Salmonella
      expressing GLU as the primary dose and soluble protein as the booster dose,
      exhibited a shift from a type 1-like to a more type 2-like immune response to GLU
      following the boost. These results indicate that S. enterica serovar Typhimurium
      is an excellent delivery vehicle for the insoluble and recombinantly expressed
      GLU of GTF and that this construct was especially effective in priming the host
      for a secondary response to soluble GLU polypeptide.

PMID- 11598029
TI  - Phosphorylcholine-dependent cross-reactivity between dental plaque bacteria and
      oxidized low-density lipoproteins.
AB  - Antibodies reactive with phosphorylcholine (PC) are ubiquitous in human sera, but
      the antigens stimulating their production and their function are not clear.
      Previous studies have shown that a significant proportion of dental plaque
      bacteria contain PC as determined by reactivity with PC-specific mouse myeloma
      proteins and monoclonal antibodies. Additionally, serum antibody concentrations
      of immunoglobulin (IgG) G anti-PC are higher in sera of individuals who have
      experienced periodontal attachment loss than those who are periodontally healthy.
      These data implicate the oral microflora as a source of antigen-stimulating anti
      PC responses. Recent data also indicate that antibodies with specificity for PC
      are elevated in ApoE-deficient mice, a model for studies of athersclerosis, and
      that such antibodies bound oxidized low-density lipoproteins (LDL) (oxLDL) in
      atherosclerotic plaques. These data prompted the hypothesis that human anti-PC
      could bind to both oral bacteria and human oxLDL, and that these antigens are
      cross-reactive. We therefore examined the ability of human anti-PC to bind to PC
      bearing strains of oral bacteria using enzyme-linked immunosorbent inhibition
      assays and by assessment of direct binding of affinity-purified human anti-PC to
      PC-bearing Actinobacillus actinomycetemcomitans. Our results indicated that PC
      bearing strains of Streptococcus oralis, Streptococcus sanguis, Haemophilus
      aphrophilus, Actinomyces naeslundii, Fusobacterium nucleatum, and A.
      actinomycetemcomitans, as well as a strain of Streptococcus pneumoniae, absorbed
      up to 80% of anti-PC IgG antibody from human sera. Furthermore, purified anti-PC
      bound to a PC-bearing strain of A. actinomycetemcomitans but only poorly to a PC
      negative strain. OxLDL also absorbed anti-PC from human sera, and oxLDL but not
      LDL reacted with up to 80% of the anti-PC in human sera. Furthermore, purified
      anti-PC bound directly to oxLDL but not to LDL. The data indicate that PC
      containing antigens on a variety of common oral bacteria are cross-reactive with
      neoantigens expressed in oxLDL. We propose that PC-bearing dental plaque
      microorganisms may induce an antibody response to PC that could influence the
      inflammatory response associated with atherosclerosis.

PMID- 11598031
TI  - Characterization of FasG segments required for 987P fimbria-mediated binding to
      piglet glycoprotein receptors.
AB  - The 987P fimbriae of enterotoxigenic strains of Escherichia coli bind to both
      glycoprotein and glycolipid receptors on the brush borders of piglet enterocytes.
      A mutation in lysine residue 117 of the adhesive subunit FasG [fasG(K117A)]
      previously shown to abrogate 987P binding to the lipid receptor sulfatide did not
      affect the interaction with the glycoprotein receptors. Both the fimbriae and the
      FasG subunits of the wild type and the fasG(K117A) mutant bound to the
      glycoprotein receptors, confirming that lysine 117 was not required for binding
      to the glycoprotein receptors. Truncated FasG molecules were used to identify
      domains required for glycoprotein receptor recognition. At least two segments
      which did not include lysine117, namely, residues 211 (glutamine) to 220 (serine)
      and 20 (aspartic acid) to 41 (serine), were shown to be involved in the FasG
      glycoprotein receptor interactions by ligand-blotting assays. Changing isoleucine
      217 or leucine 215 of FasG to alanine abolished the property of a truncated FasG
      fusion protein to inhibit 987P recognition of its glycoprotein receptors. Thus,
      the K117 residue of FasG is required only for binding to the glycolipid receptor,
      whereas the newly identified hydrophobic residues of the FasG subunit are
      required specifically for the recognition of the glycoprotein receptor. Taken
      together, our data indicate that different residues of the FasG adhesin are
      important in 987P fimbrial binding to sulfatide and glycoprotein receptors,
      suggesting different mechanisms of interaction.

PMID- 11598030
TI  - Infection with Mycobacterium avium differentially regulates the expression of
      iron transport protein mRNA in murine peritoneal macrophages.
AB  - Iron is an important element for the growth of microorganisms as well as in the
      defense of the host by serving as a catalyst for the generation of free radicals
      via the Fenton/Haber-Weiss reactions. The iron transporter natural resistance
      associated macrophage protein 1 (Nramp1) confers resistance to the growth of a
      variety of intracellular pathogens including Mycobacterium avium. Recently
      several other proteins that are involved in iron transport, including the highly
      homologous iron transporter Nramp2 and the transferrin receptor-associated
      protein HFE (hereditary hemochromatosis protein), have been described. The
      relationship of these proteins to host defense and to the growth of intracellular
      pathogens is not known. Here, we report that infection with M. avium
      differentially regulates mRNA expression of the proteins associated with iron
      transport in murine peritoneal macrophages. Both Nramp1 and Nramp2 mRNA levels
      increase following infection, while the expression of transferrin receptor mRNA
      decreases. The level of expression of HFE mRNA remains unchanged. The difference
      in the expression of the mRNA of these proteins following infection or cytokine
      stimulation suggests that they may play an important role in host defense by
      maintaining a delicate balance between iron availability for host defense and at
      the same time limiting iron availability for microbial growth.

PMID- 11598032
TI  - Administration of superantigens protects mice from lethal Listeria monocytogenes
      infection by enhancing cytotoxic T cells.
AB  - Superantigens stimulate T-cell-receptor Vbeta-selective T-cell proliferation
      accompanying the release of cytokines, which may eventually protect the host from
      microbial infections. We investigated here whether superantigens can rescue the
      host from lethal bacterial infection. Mice were pretreated with Staphylococcus
      aureus enterotoxin B (SEB) 1 and 2 days before bacterial infection, and the
      mortality of infected mice was assessed. SEB pretreatment protected mice from
      lethal infection with Listeria monocytogenes but not from lethal infection with
      Streptococcus pyogenes. This enhanced protection was also observed upon
      pretreatment with recombinant streptococcal pyrogenic exotoxin A. Furthermore, L.
      monocytogenes-specific delayed-type hypersensitivity (DTH) due to type 1 helper T
      (Th1) cells and the cytotoxicity of CD8(+) T cells were significantly enhanced
      after SEB administration and bacterial infection. Depletion of either CD4(+) T
      cells or CD8(+) T cells in SEB-pretreated mice completely abolished this
      protection. This phenomenon was ascribed to the elimination of L. monocytogenes
      specific CD8(+) cytotoxic T lymphocytes (CTL). It was found that CD4(+) T cells
      contributed to the induction of the CTL populations. Furthermore, SEB
      pretreatment of heat-killed L. monocytogenes-immunized mice enhanced the
      protection from challenge of L. monocytogenes. Taken together, these results
      indicated that administrations of superantigens protected mice from infection
      with L. monocytogenes, which was dependent on the enhanced L. monocytogenes
      specific CTL activity in the presence of CD4(+) T cells, and superantigens
      exhibited adjuvant activity in the immunization against intracellular pathogens.

PMID- 11598033
TI  - Enhanced gamma interferon production through activation of Valpha14(+) natural
      killer T cells by alpha-galactosylceramide in interleukin-18-deficient mice with
      systemic cryptococcosis.
AB  - We showed recently that activation of Valpha14(+) natural killer T cells (NKT
      cells) by alpha-galactosylceramide (alpha-GalCer) resulted in increased gamma
      interferon (IFN-gamma) production and host resistance to intravenous infection
      with Cryptococcus neoformans. In other studies, interleukin-18 (IL-18) activated
      NKT cells in collaboration with IL-12, suggesting the possible contribution of
      this cytokine to alpha-GalCer-induced IFN-gamma synthesis. Here we examined the
      role of IL-18 in alpha-GalCer-induced Th1 response by using IL-18KO mice with
      this infection. In these mice, levels of IFN-gamma in serum and its synthesis in
      vitro by spleen cells stimulated with live organisms were not reduced, but rather
      enhanced, compared to those in wild-type (WT) mice, while such production was
      completely absent in IL-12KO mice. The enhanced production of IFN-gamma
      correlated with increased IL-12 synthesis but not with reduced production of IL
      4, which was rather increased. IFN-gamma synthesis in IL-18KO mice was abolished
      by neutralizing anti-IL-12 antibody and significantly inhibited by neutralization
      of endogenous IL-4 with a specific monoclonal antibody. In addition,
      administration of recombinant IL-4 significantly enhanced the production of IFN
      gamma in WT mice. Finally, the enhanced production of IFN-gamma in IL-18KO mice
      correlated with increased host defense against cryptococcal infection, as
      indicated by enhancement in alpha-GalCer-related clearance of microorganisms. Our
      results indicated that in IL-18KO mice, IFN-gamma synthesis was enhanced through
      overproduction of IL-12 and IL-4 after intravenous infection with C. neoformans
      and a ligand-specific activation of Valpha14(+) NKT cells.

PMID- 11598035
TI  - toxB gene on pO157 of enterohemorrhagic Escherichia coli O157:H7 is required for
      full epithelial cell adherence phenotype.
AB  - Adherence of enterohemorrhagic Escherichia coli (EHEC) to the intestinal
      epithelium is critical for initiation of a bacterial infection. An in vitro
      infection study previously indicated that EHEC bacteria initially adhere
      diffusely and then proliferate to develop MC, a process that is mediated by
      various secreted proteins, such as EspA, EspB, EspD, Tir, and intimin, as well as
      other putative adherence factors. In the present study, we investigated the role
      of a large 93-kb plasmid (pO157) in the adherence of O157:H7 (O157Sakai) and
      found the toxB gene to be involved in the full adherence phenotype. A pO157-cured
      strain of O157Sakai (O157Cu) developed microcolonies on Caco-2 cells; however,
      the number of microcolonies was lower than that of O157Sakai, as were the
      production and secretion levels of EspA, EspB, and Tir. Introduction of a mini
      pO157 plasmid (pIC37) composed of the toxB and ori regions restored full
      adherence capacity to O157Cu, including production and secretion of the proteins.
      In contrast, introduction of a pO157 mutant possessing toxB::Km into O157Cu could
      not restore the full adherence phenotype. Expression of truncated versions of His
      tagged ToxB also promoted EspB production and/or secretion by O157Cu. These
      results suggest that ToxB contributes to the adherence of EHEC to epithelial
      cells through promotion of the production and/or secretion of type III secreted
      proteins.

PMID- 11598034
TI  - Critical role for tumor necrosis factor alpha in controlling the number of
      lumenal pathogenic bacteria and immunopathology in infectious colitis.
AB  - Infection of mice with the intestinal bacterial pathogen Citrobacter rodentium
      results in colonic mucosal hyperplasia and a local Th1 inflammatory response
      similar to that seen in mouse models of inflammatory bowel disease. In these
      latter models, and in patients with Crohn's disease, neutralization of tumor
      necrosis factor alpha (TNF-alpha) is of therapeutic benefit. Since there is no
      information on the role of TNF-alpha in either immunity to noninvasive bacterial
      pathogens or on the role of TNF-alpha in the immunopathology of infectious
      colitis, we investigated C. rodentium infection in TNFRp55(-/-) mice. In TNFRp55(
      /-) mice, there were higher colonic bacterial burdens, but the organisms were
      cleared at the same rate as C57BL/6 mice, showing that TNF-alpha is not needed
      for protective antibacterial immunity. The most striking feature of infection in
      TNFRp55(-/-) mice, however, was the markedly enhanced pathology, with increased
      mucosal weight and thickness, increased T-cell infiltrate, and a markedly greater
      mucosal Th1 response. Interleukin-12 p40 transcripts were markedly elevated in C.
      rodentium-infected TNFRp55(-/-) mice, and this was associated with enhanced
      mucosal STAT4 phosphorylation. TNF-alpha is not obligatory for protective
      immunity to C. rodentium in mice; however, it appears to play some role in
      downregulating mucosal pathology and Th1 immune responses.

PMID- 11598036
TI  - HLA-B27 expression does not modulate intracellular Chlamydia trachomatis
      infection of cell lines.
AB  - Chlamydia trachomatis is an obligate intracellular pathogen. Infection of
      susceptible individuals with this bacterium can trigger the development of
      reactive arthritis, an acute inflammation that is associated with the expression
      of the class I major histocompatibility antigen, HLA-B27. Other facultative
      intracellular pathogens, such as Yersinia and Salmonella spp., are also known
      triggers of reactive arthritis. Previous studies report conflicting results
      concerning whether the presence of HLA-B27 modulates the infection of cells with
      these enteric pathogens. In the present study, we have examined whether the
      expression of HLA-B27 can influence the infection of cell lines with C.
      trachomatis and also whether the replication of these bacteria is altered in HLA
      B27-expressing cell lines. To do this, we have used a sensitive flow cytometric
      approach. We fixed and permeabilized cells and used fluorescein isothiocyanate
      conjugated monoclonal antibody specific for chlamydia lipopolysaccharide to
      detect intracellular bacteria. The staining pattern obtained closely resembled
      the intracellular life cycle of chlamydia, with the appearance of brightly
      staining cells correlating to the microscopic detection of mature inclusion
      bodies. Moreover, since the percentage of cells that stained with the antibody
      was proportional to the infectious inoculum used, we were able to use the
      technique to quantitate the number of infectious organisms recoverable from
      infected cell lines. An important component of our study was the use of heparin
      to prevent reinfection of cells and thus enable the infection to be followed from
      a discrete time point. Our results suggest that HLA-B27 influences neither the
      infection nor replication of C. trachomatis serovar L2 within cell lines.
      Consequently, the role of HLA-B27 in the pathogenesis of reactive arthritis may
      lie downstream of the invasion and replication stages of the triggering
      pathogenic infection.

PMID- 11598037
TI  - Enhanced antimycobacterial response to recombinant Mycobacterium bovis BCG
      expressing latency-associated peptide.
AB  - With a view to exploring the role of transforming growth factor beta (TGF-beta)
      during mycobacterial infection, recombinant clones of bacillus Calmette-Guerin
      (BCG) were engineered to express the natural antagonist of TGF-beta, latency
      activated peptide (LAP). Induction of TGF-beta activity was reduced when
      macrophages were infected with BCG expressing the LAP construct (LAP-BCG). There
      was a significant reduction in the growth of LAP-BCG in comparison to that of
      control BCG following intravenous infection in a mouse model. The enhanced
      control of mycobacterial replication was associated with an increase in the
      production of gamma interferon by splenocytes challenged during the acute stage
      of infection but with a diminished recall response assessed after 13 weeks. Organ
      weight and hydroxyproline content, representing tissue pathology, were also lower
      in mice infected with LAP-BCG. The results are consistent with the hypothesis
      that TGF-beta has a detrimental effect on mycobacterial immunity. While a
      reduction in TGF-beta activity augments the initial response to BCG vaccination,
      early bacterial clearance may adversely affect the induction of a long-term
      memory response by LAP-BCG.

PMID- 11598038
TI  - Absence of a cysteine protease effect on bacterial virulence in two murine models
      of human invasive group A streptococcal infection.
AB  - The cysteine protease of group A streptococci has been suggested to contribute to
      the pathogenesis of invasive infection through degradation of host tissue,
      activation of the host inflammatory response, release of protective molecules
      from the bacterial cell surface, or other mechanisms. However, studies of the
      effects on virulence of inactivating the cysteine protease gene speB have yielded
      conflicting results. In some reports, a speB mutant was relatively avirulent in
      mouse models of invasive infection whereas little or no attenuation of virulence
      was observed in other studies of similar mutant strains. Possible reasons for
      these discordant results include differences in the streptococcal strains from
      which the speB mutants were derived, differences in the infection models
      employed, or unintended effects on another virulence determinant(s) that arose
      during the derivation of a speB mutant. We attempted to clarify these issues by
      characterizing the phenotypic properties and relative virulence in mice of two
      speB mutant strains, both derived from wild-type strain AM3: speB mutant AM3speB,
      which has been shown to be markedly attenuated in virulence in mice after
      intraperitoneal or subcutaneous challenge, and AM3speBOmega, a new mutant strain
      derived for this investigation. Both mutant strains were negative for protease
      activity, as expected, and both produced wild-type amounts of type 3 M protein
      and streptolysin O. However, AM3speB produced significantly less cell-associated
      hyaluronic acid capsule than did parent strain AM3 or strain AM3speBOmega.
      Compared to wild-type strain AM3, AM3speB was more sensitive to opsonophagocytic
      killing in vitro and was significantly less virulent in mice after
      intraperitoneal challenge. By contrast, AM3speBOmega was fully resistant to
      phagocytosis and did not differ significantly from the wild-type strain in mouse
      virulence after an intraperitoneal or subcutaneous challenge. We concluded that
      previous reports attributing loss of virulence in strain AM3speB to inactivation
      of speB are in error. Within the limitations of the models used, we found no
      effect of cysteine protease on invasive streptococcal infection.

PMID- 11598039
TI  - Uropathogenic Escherichia coli potentiates type 1 pilus-induced apoptosis by
      suppressing NF-kappaB.
AB  - Urinary tract infections (UTIs) are among the most common inflammatory diseases.
      Acute UTIs are typically caused by type 1-piliated Escherichia coli and result in
      urothelial apoptosis, local cytokine release, and neutrophil infiltration. To
      examine the urothelial apoptotic response, a human urothelial cell line was
      incubated with various E. coli isolates and was then characterized by flow
      cytometry. Uropathogenic E. coli (UPEC) induced rapid urothelial apoptosis that
      was strictly dependent upon interactions mediated by type 1 pili. Interestingly,
      nonpathogenic HB101 E. coli expressing type 1 pili induced apoptosis at
      approximately 50% of the level induced by UPEC, suggesting that pathogenic
      strains contribute to apoptosis by pilus-independent mechanisms. Consistent with
      this possibility, UPEC blocked activity of an NF-kappaB-dependent reporter in
      response to inflammatory stimuli, yet this effect was independent of functional
      type 1 pili and was not mediated by laboratory strains of E. coli. UPEC
      suppressed NF-kappaB by stabilizing IkappaBalpha, and UPEC rapidly altered
      cellular signaling pathways. Finally, blocking NF-kappaB activity increased the
      level of piliated HB101-induced apoptosis to the level of apoptosis induced by
      UPEC. These results suggest that UPEC blocks NF-kappaB and thereby enhances type
      1 pili-induced apoptosis as a component of the uropathogenic program.

PMID- 11598040
TI  - Effects of alum adjuvant or a booster dose on immunogenicity during clinical
      trials of group B streptococcal type III conjugate vaccines.
AB  - Phase 1 and 2 clinical trials of group B streptococcal (GBS) capsular
      polysaccharide (CPS)-protein conjugate vaccines in healthy adults have
      demonstrated their safety and improved immunogenicity compared with uncoupled
      CPSs. Two recent trials sought to determine (i) whether adsorption of conjugate
      vaccine to aluminum hydroxide would improve immunogenicity and (ii) whether the
      CPS-specific immunoglobulin G (IgG) response could be boosted by administration
      of a second dose. Adsorption of GBS type III CPS-tetanus toxoid (III-TT)
      conjugate vaccine to alum did not improve the immune response to a 12.5-microg
      dose in healthy adult recipients. Four weeks after vaccination, the geometric
      mean antibody concentrations (GMCs) for the 15 recipients of III-TT with or
      without alum were 3.3 and 3.6 microg/ml, respectively. In the second trial, 36
      healthy adults vaccinated previously with GBS III-TT conjugate were given a
      second 12.5-microg dose 21 months later. At 4 weeks after the second dose, the
      GMCs of type III CPS-specific IgG were similar to those measured 4 weeks after
      the primary vaccination, suggesting a lack of a booster response. However, 8
      (22%) of the 36 participants who had undetectable III CPS-specific IgG (<0.05
      microg/ml) before the first dose of III-TT conjugate exhibited a booster response
      to the second dose, with a fourfold-greater GMC of type III CPS-specific IgG than
      after the initial immunization. These results suggest that prior natural exposure
      to type III GBS or a related antigen may be responsible for the brisk IgG
      response to CPS noted in most adults after vaccination. However, a second dose of
      GBS III-TT conjugate vaccine may be required for adults whose initial CPS
      specific IgG concentrations are very low and would also restore the initial peak
      specific III CPS-IgG in responders to previous vaccination.

PMID- 11598041
TI  - Immunization with components of two iron uptake ABC transporters protects mice
      against systemic Streptococcus pneumoniae infection.
AB  - There has been considerable recent research into protein based Streptococcus
      pneumoniae vaccines as alternatives to the existing capsular antigen vaccines.
      PiuA and PiaA (formerly Pit1A and Pit2A) are recently identified lipoprotein
      components of S. pneumoniae iron uptake ABC transporters which are required for
      full virulence and are likely to be expressed on the surface of the bacterial
      cell membrane. We investigated the efficacy of recombinant PiuA and PiaA proteins
      at eliciting protective immunity in mice against systemic infection with S.
      pneumoniae. Both recombinant PiuA and PiaA generated antibody responses that
      cross-reacted with each other but not with pneumolysin and reacted with identical
      proteins from nine different S. pneumoniae serotypes. Mice immunized with
      recombinant PiuA and PiaA were protected against systemic challenge to a degree
      similar to those immunized with an existing protein vaccine candidate, PdB (a
      genetically modified pneumolysin toxoid). Immunization with a combination of both
      PiuA and PiaA resulted in additive protection and was highly protective against
      systemic infection with S. pneumoniae. PiuA and PiaA are therefore promising
      additional candidates for a novel S. pneumoniae vaccine using protein antigens.

PMID- 11598042
TI  - Identification and characterization of the hemophore-dependent heme acquisition
      system of Yersinia pestis.
AB  - Yersinia pestis possesses a heme-protein acquisition system (Hmu) that allows it
      to utilize heme and heme-protein complexes as the sole sources of iron. Analysis
      of the Y. pestis CO92 genomic sequence revealed a second heme-protein acquisition
      gene cluster that shares homology with the hemophore-dependent heme acquisition
      system (Has system) of Serratia marcescens. This locus consisted of the hasR(yp)
      receptor gene, the hasA(yp) hemophore gene, and genes encoding components of the
      HasA(yp) dedicated ABC transporter factor (hasDE(yp)), as well as a tonB
      homologue (hasB(yp)). By using a reconstituted secretion system in Escherichia
      coli, we showed that HasA(yp) is a secreted heme-binding protein and that
      expression of HasA(yp) is iron regulated in E. coli. The use of a transcriptional
      reporter fusion showed that the hasRADEB promoter is Fur regulated and has
      increased activity at 37 degrees C. Hemoglobin utilization via the Has(yp) system
      was studied with both E. coli and Y. pestis, for which has and has hmu mutant
      strains were used. No contribution of the Has system to heme utilization was
      observed in either E. coli or Y. pestis under the conditions we tested.
      Previously it was shown that a deletion of the Hmu system had no effect on the
      virulence of Y. pestis in a mouse model of bubonic plague. An Hmu(-) Has(-)
      double mutant also retained full virulence in this model of infection. This
      report constitutes the first attempt to investigate the contribution of the
      hemophore-dependent heme acquisition system in bacterial pathogenicity.

PMID- 11598043
TI  - Intranasal vaccination with pneumococcal surface protein A and interleukin-12
      augments antibody-mediated opsonization and protective immunity against
      Streptococcus pneumoniae infection.
AB  - Streptococcus pneumoniae is a major pathogen in humans that enters the host
      primarily through the respiratory tract. Targeting mucosal surfaces directly may
      therefore be an optimal approach for vaccination to prevent bacterial
      colonization and invasive disease. We have previously demonstrated the
      effectiveness of interleukin-12 (IL-12) delivered intransally (i.n.) as an
      antiviral respiratory adjuvant. In this study, we examined the effects of i.n. IL
      12 treatment on induction of protective humoral immunity against S. pneumoniae.
      Immunization i.n. with pneumococcal surface protein A (PspA) and IL-12 resulted
      in enhanced lung IL-10 mRNA expression and marked augmentation of respiratory and
      systemic immunoglobulin G1 (IgG1), IgG2a, and IgA antibody levels compared to
      those in animals receiving PspA alone. In addition, i.n. vaccination with PspA
      and IL-12 provided increased protection against nasopharyngeal carriage. Flow
      cytometric analysis revealed a threefold increase in antibody-mediated,
      complement-independent opsonic activity in the sera of PspA- and IL-12-treated
      animals, which was mainly contributed by IgG2a and, to a lesser extent, IgA.
      Passive transfer of these immune sera conferred complete protection from death
      upon systemic pneumococcal challenge. These findings demonstrate the
      effectiveness of combining PspA and IL-12 at mucosal sites to achieve optimal
      antibody-mediated opsonization and killing of S. pneumoniae.

PMID- 11598044
TI  - Salmonella DNA adenine methylase mutants confer cross-protective immunity.
AB  - Salmonella isolates that lack or overproduce DNA adenine methylase (Dam) elicited
      a cross-protective immune response to different Salmonella serovars. The
      protection afforded by the Salmonella enterica serovar Typhimurium Dam vaccine
      was greater than that elicited in mice that survived a virulent infection. S.
      enterica serovar Typhimurium Dam mutant strains exhibited enhanced sensitivity to
      mediators of innate immunity such as antimicrobial peptides, bile salts, and
      hydrogen peroxide. Also, S. enterica serovar Typhimurium Dam(-) vaccines were not
      immunosuppressive; unlike wild-type vaccines, they failed to induce increased
      nitric oxide levels and permitted a subsequent robust humoral response to
      diptheria toxoid antigen in infected mice. Dam mutant strains exhibited a low
      grade persistence which, coupled with the nonimmunosuppression and the ectopic
      protein expression caused by altered levels of Dam, may provide an expanded
      source of potential antigens in vaccinated hosts.

PMID- 11598045
TI  - Association of mitogen-activated protein kinase pathways with gingival epithelial
      cell responses to Porphyromonas gingivalis infection.
AB  - Mitogen-activated protein (MAP) kinase pathways are key factors in host signaling
      events and can also play important roles in the internalization of pathogenic
      bacteria by host cells. Porphyromonas gingivalis, a periodontal pathogen, can
      efficiently invade human gingival epithelial cells (GECs). In this study, we
      examined the activation of MAP kinase pathways in GECs infected with P.
      gingivalis. c-Jun N-terminal kinase (JNK) was activated after 5 min of infection
      with P. gingivalis, whereas noninvasive Streptococcus gordonii did not have a
      significant effect on JNK activation. In contrast, extracellular signal-regulated
      kinase (ERK) 1/2 was downregulated in a dose-dependent manner by P. gingivalis,
      but not by S. gordonii, after a 15-min exposure. Nonmetabolically active P.
      gingivalis cells were unable to modulate MAP kinase activity. U0126, a specific
      inhibitor of MEK1/2 (ERK1/2 kinase), and toxin B, a specific inhibitor of Rho
      family GTPases, had no effect on P. gingivalis invasion. Genistein, a tyrosine
      protein kinase inhibitor, blocked uptake of P. gingivalis. The transcriptional
      regulator NF-kappaB was not activated by P. gingivalis. These results suggest
      that P. gingivalis can selectively target components of the MAP kinase pathways.
      ERK1/2, while not involved in P. gingivalis invasion of GECs, may be
      downregulated by internalized P. gingivalis. Activation of JNK is associated with
      the invasive process of P. gingivalis.

PMID- 11598046
TI  - Characterization of a Brucella species 25-kilobase DNA fragment deleted from
      Brucella abortus reveals a large gene cluster related to the synthesis of a
      polysaccharide.
AB  - In the present study we completed the nucleotide sequence of a Brucella
      melitensis 16M DNA fragment deleted from B. abortus that accounts for 25,064 bp
      and show that the other Brucella spp. contain the entire 25-kb DNA fragment. Two
      short direct repeats of four nucleotides, detected in the B. melitensis 16M DNA
      flanking both sides of the fragment deleted from B. abortus, might have been
      involved in the deletion formation by a strand slippage mechanism during
      replication. In addition to omp31, coding for an immunogenic protein located in
      the Brucella outer membrane, 22 hypothetical genes were identified. Most of the
      proteins that would be encoded by these genes show significant homology with
      proteins involved in the biosynthesis of polysaccharides from other bacteria,
      suggesting that they might be involved in the synthesis of a Brucella
      polysaccharide that would be a heteropolymer synthesized by a Wzy-dependent
      pathway. This polysaccharide would not be synthesized in B. abortus and would be
      a polysaccharide not identified until present in the genus Brucella, since all of
      the known polysaccharides are synthesized in all smooth Brucella species.
      Discovery of a novel polysaccharide not synthesized in B. abortus might be
      interesting for a better understanding of the pathogenicity and host preference
      differences observed between the Brucella species. However, the possibility that
      the genes detected in the DNA fragment deleted in B. abortus no longer lead to
      the synthesis of a polysaccharide must not be excluded. They might be a remnant
      of the common ancestor of the alpha-2 subdivision of the class Proteobacteria,
      with some of its members synthesizing extracellular polysaccharides and, as
      Brucella spp., living in association with eukaryotic cells.

PMID- 11598047
TI  - Analysis of cytokines in the early development of gastric secondary lymphoid
      follicles in Helicobacter pylori-infected BALB/c mice with neonatal thymectomy.
AB  - Immunological interaction between the host and Helicobacter pylori seems to play
      a critical role in follicular formation in gastric mucosa. We reported H. pylori
      induced follicular gastritis model using neonatally thymectomized mice. In this
      study, we investigated the involvement of various cytokines in this model. BALB/c
      mice were thymectomized on the third day after birth (nTx). At 6 weeks old, these
      mice were orally infected with H. pylori. Histological studies showed that
      follicular formation occurred from 8 weeks after the infection and that most of
      the infiltrating lymphocytes were CD4(+) and B cells. Neutrophils increased
      transiently at 1 week after the infection. Gamma interferon, interleukin-7 (IL
      7), and IL-7 receptor were expressed in the stomach of the nTx mice irrespective
      of the infection. In contrast, expressions of the tumor necrosis factor alpha, IL
      4 and lymphotoxin-alpha genes were remarkably upregulated by the infection. Our
      findings suggest that follicular formation may require cooperative involvement of
      a Th2-type immune response, tumor necrosis factor alpha and lymphotoxin-alpha in
      addition to the Th1-type immune response in H. pylori-induced gastritis in nTx
      mice.

PMID- 11598048
TI  - Patterns of chemokine expression in models of Schistosoma mansoni inflammation
      and infection reveal relationships between type 1 and type 2 responses and
      chemokines in vivo.
AB  - To explore the roles of chemokines in type 1 and type 2 responses in vivo, we
      examined mRNA expression for a panel of up to 17 chemokines in experimental mouse
      models using Schistosoma mansoni. These studies revealed that Mig (monokine
      induced by gamma interferon), cytokine-responsive gene 2/10-kDa interferon
      inducible protein, RANTES, lymphotactin, macrophage inflammatory protein 1beta
      (MIP-1beta), JE/monocyte chemoattractant protein 1, and MIP-2 are associated with
      type 1 egg-induced responses and that thymus-derived chemotactic agent 3 (TCA3),
      eotaxin, MIP-1alpha, and MIP-1gamma are associated with type 2 egg-induced
      responses. After cercarial infection, both type 1-associated and type 2
      associated chemokines were elevated in the livers of infected mice presensitized
      with eggs and recombinant interleukin-12 (rIL-12), a regimen that diminishes
      pathology. Neutralization of IL-12 or gamma interferon during egg deposition
      reversed the effects of prior treatment with rIL-12, leading to a return to
      larger granulomas; persistently elevated expression of TCA3, eotaxin, and MIP
      1alpha; and a marked reduction in the expression of type 1-associated chemokines
      despite the maintenance of a dominant type 1 cytokine response in the draining
      lymph nodes. Our findings suggest that there are patterns of coordinate chemokine
      expression characteristic of type 1 and type 2 responses in vivo; that the cells
      recruited by a given pattern of chemokines may differ, depending on the
      composition of peripheral populations; and that patterns of tissue expression of
      chemokines may determine the character of an inflammatory response independently
      of the dominant pattern of differentiation of antigen-specific T cells. Our data
      reveal new relationships between chemokines and polarized immune responses and
      suggest that end organ inflammation might be altered by chemokine blockade
      without necessitating reversal of the phenotype of the majority of differentiated
      T cells.

PMID- 11598049
TI  - Outer membrane targeting of passenger proteins by the vacuolating cytotoxin
      autotransporter of Helicobacter pylori.
AB  - Helicobacter pylori produces a number of proteins associated with the outer
      membrane, including adhesins and the vacuolating cytotoxin. These proteins are
      supposed to integrate into the outer membrane by beta-barrel structures,
      characteristic of the family of autotransporter proteins. By using the SOMPES
      (shuttle vector-based outer membrane protein expression) system for outer
      membrane protein production, we were able to functionally express in H. pylori
      the cholera toxin B subunit genetically fused to the C-terminal VacA domain. We
      demonstrate that the fusion protein is translocated to the H. pylori outer
      membrane and that the CtxB domain is exposed on the H. pylori surface. Thus, we
      provide the first experimental evidence that the C-terminal beta-domain of VacA
      can transport a foreign passenger protein to the H. pylori surface and hence acts
      as a functional autotransporter.

PMID- 11598050
TI  - Biochemical and biological characterization of the protective Leishmania pifanoi
      amastigote antigen P-8.
AB  - The Leishmania pifanoi amastigote antigen P-8 has been previously shown to induce
      protective immunity in a murine model of cutaneous leishmaniasis (L. Soong, S. M.
      Duboise, P. Kima, and D. McMahon-Pratt, Infect. Immun. 63:3559-3566, 1995). As
      this antigen is of interest for further vaccine studies, the biochemical
      characterization of P-8 was undertaken. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, Western-blot analysis, and gel filtration chromatography
      revealed that P-8 antigen consisted of two proteoglycolipid complexes. The P-8
      epitope is associated with the L. pifanoi amastigote-specific glycolipid
      components found in the two complexes. The P-8 complex 1 (P-8c1) consists of a 56
      kDa serine metalloproteinase, apolipoprotein E (derived from fetal bovine serum),
      and amastigote-specific glycolipids. The P-8 complex 2 (P-8c2) consists of a 31
      kDa cysteine proteinase associated with amastigote glycolipids. Biochemical
      analyses suggest that the P-8 antigenic glycolipids may be distinct from
      previously described Leishmania glycolipids (glycosylinositol-phospholipids and
      sphingoglycolipids). Protective immunity studies revealed that P-8c1 (serine
      metalloproteinase-glycolipid complex) confers comparable protection against
      infection as immunopurified P-8. The isolated P-8c2 (cysteine proteinase
      glycolipid complex) does not provide significant protection, nor does stimulation
      with P-8c2 result in significant T-cell activation in P-8- or P-8c2-vaccinated
      mice. Consequently, the P-8c1 complex appears to be the immunodominant component
      of P-8.

PMID- 11598051
TI  - Type III secretion-dependent cell cycle block caused in HeLa cells by
      enteropathogenic Escherichia coli O103.
AB  - Rabbit enteropathogenic Escherichia coli (EPEC) O103 induces in HeLa cells an
      irreversible cytopathic effect characterized by the recruitment of focal
      adhesions, formation of stress fibers, and inhibition of cell proliferation. We
      have characterized the modalities of the proliferation arrest and investigated
      its underlying mechanisms. We found that HeLa cells that were exposed to the
      rabbit EPEC O103 strain E22 progressively accumulated at 4C DNA content and did
      not enter mitosis. A significant proportion of the cells were able to reinitiate
      DNA synthesis without division, leading to 8C DNA content. This cell cycle
      inhibition by E22 was abrogated in mutants lacking EspA, -B, and -D and was
      restored by transcomplementation. In contrast, intimin and Tir mutants retained
      the antiproliferative effect. The cell cycle arrest was not a direct consequence
      of the formation of stress fibers, since their disruption by toxins during
      exposure to E22 did not reverse the cell cycle inhibition. Likewise, the cell
      cycle arrest was not dependent on the early tyrosine dephosphorylation events
      triggered by E22 in the cells. Two key partner effectors controlling entry into
      mitosis were also investigated: cyclin B1 and the associated cyclin-dependent
      kinase 1 (Cdk1). Whereas cyclin B1 was not detectably affected in E22-exposed
      cells, Cdk1 was maintained in a tyrosine-phosphorylated inactive state and lost
      its affinity for p13(suc1)-agarose beads. This shows that Cdk1 is implicated in
      the G2/M arrest caused by EPEC strain E22.

PMID- 11598052
TI  - Capsule production and growth phase influence binding of complement to
      Staphylococcus aureus.
AB  - Complement-mediated opsonization of bacteria by C3 binding is an important
      component of the host innate immune system. Little information is available
      concerning the interaction between complement proteins and capsule type 5 and 8
      Staphylococcus aureus strains, even though these isolates are responsible for
      approximately 70% of human staphylococcal infections. To investigate the
      importance of an intact complement pathway in an experimental staphylococcal
      infection, control and C3-depleted mice were challenged intravenously with 10(7)
      CFU of a serotype 5 S. aureus isolate. Whereas only 8% of the control mice
      succumbed to the infection, 64% of the complemented-depleted animals died. In
      vitro parameters of C3 binding to two heavily encapsulated (CP++) strains, three
      encapsulated (CP+) strains, and an isogenic capsule-negative (CP-) mutant were
      examined. The alternative pathway contributed 90% of C3 binding in 20% serum at
      30 min, whereas it accounted for only 13% of C3 binding in 2% serum. Stationary
      phase organisms bound only 10% as much C3 as mid-log-phase organisms; this was
      only in part due to capsule. When the S. aureus strains were cultivated on solid
      medium, the CP++ isolates bound 50% less C3 than CP+ strains; a CP+ strain bound
      42% less C3 than the CP- mutant. Both C3b and iC3b fragments of C3 bound to S.
      aureus cells, and about one-third of the bound C3 was shed from the
      staphylococcal surface as iC3b, regardless of the CP phenotype of the strain.
      Thus, the phase of growth and presence of capsule are critical to opsonization.

PMID- 11598053
TI  - Regulated expression and effect of galectin-1 on Trypanosoma cruzi-infected
      macrophages: modulation of microbicidal activity and survival.
AB  - Galectin-1 is a beta-galactoside-binding protein with potent anti-inflammatory
      and immunoregulatory effects. However, its expression and function have not been
      assessed in the context of an infectious disease. The present study documents,
      for the first time, the regulated expression of galectin-1 in the context of an
      infectious process and its influence in the modulation of macrophage microbicidal
      activity and survival. A biphasic modulation in parasite replication and cell
      viability was observed when macrophages isolated from Trypanosoma cruzi-infected
      mice were exposed to increasing concentrations of galectin-1. While low
      concentrations of this protein increased parasite replication and did not affect
      macrophage survival, higher inflammatory doses of galectin-1 were able to commit
      cells to apoptosis and inhibited parasite replication. Furthermore, galectin-1 at
      its lowest concentration was able to down-regulate critical mediators for
      parasite killing, such as interleukin 12 (IL-12) and nitric oxide, while it did
      not affect IL-10 secretion. Finally, endogenous galectin-1 was found to be up
      regulated and secreted by the J774 macrophage cell line cultured in the presence
      of trypomastigotes. This result was extended in vivo by Western blot analysis,
      flow cytometry, and reverse transcription-PCR using macrophages isolated from T.
      cruzi-infected mice. This study documents the first association between galectin
      1's immunoregulatory properties and its role in infection and provides new clues
      to the understanding of the mechanisms implicated in host-parasite interactions
      during Chagas' disease and other parasite infections.

PMID- 11598054
TI  - Candida albicans is phagocytosed, killed, and processed for antigen presentation
      by human dendritic cells.
AB  - Candida albicans is a component of the normal flora of the alimentary tract and
      also is found on the mucocutaneous membranes of the healthy host. Candida is the
      leading cause of invasive fungal disease in premature infants, diabetics, and
      surgical patients, and of oropharyngeal disease in AIDS patients. As the
      induction of cell-mediated immunity to Candida is of critical importance in host
      defense, we sought to determine whether human dendritic cells (DC) could
      phagocytose and degrade Candida and subsequently present Candida antigens to T
      cells. Immature DC obtained by culture of human monocytes in the presence of
      granulocyte-macrophage colony-stimulating factor and interleukin-4 phagocytosed
      unopsonized Candida in a time-dependent manner, and phagocytosis was not enhanced
      by opsonization of Candida in serum. Like macrophages (Mphi), DC recognized
      Candida by the mannose-fucose receptor. Upon ingestion, DC killed Candida as
      efficiently as human Mphi, and fungicidal activity was not enhanced by the
      presence of fresh serum. Although phagocytosis of Candida by DC stimulated the
      production of superoxide anion, inhibitors of the respiratory burst (or NO
      production) did not inhibit killing of Candida, even when phagocytosis was
      blocked by preincubation of DC with cytochalasin D. Further, although apparently
      only modest phagolysosomal fusion occurred upon DC phagocytosis of Candida,
      killing of Candida under anaerobic conditions was almost equivalent to killing
      under aerobic conditions. Finally, DC stimulated Candida-specific lymphocyte
      proliferation in a concentration-dependent manner after phagocytosis of both
      viable and heat-killed Candida cells. These data suggest that, in vivo, such
      interactions between DC and C. albicans may facilitate the induction of cell
      mediated immunity.

PMID- 11598055
TI  - Bordetella pertussis autoregulates pertussis toxin production through the
      metabolism of cysteine.
AB  - Pertussis toxin (Ptx) expression and secretion in Bordetella pertussis are
      regulated by a two-component signal transduction system encoded by the bvg
      regulatory locus. However, it is not known whether the metabolic pathways and
      growth state of the bacterium influence synthesis and secretion of Ptx and other
      virulence factors. We have observed a reduction in the concentration of Ptx per
      optical density unit midway in fermentation. Studies were conducted to identify
      possible factors causing this reduction and to develop culture conditions that
      optimize Ptx expression. Medium reconstitution experiments demonstrated that
      spent medium and a fraction of this medium containing components with a molecular
      weight of <3,000 inhibited the production of Ptx. A complete flux analysis of the
      intermediate metabolism of B. pertussis revealed that the sulfur-containing amino
      acids methionine and cysteine and the organic acid pyruvate accumulated in the
      media. In fermentation, a large amount of internal sulfate (SO4(2-)) was observed
      in early stage growth, followed by a rapid decrease as the cells entered into
      logarithmic growth. This loss was later followed by the accumulation of large
      quantities of SO4(2-) into the media in late-stage fermentation. Release of SO4(2
      ) into the media by the cells signaled the decoupling of cell growth and Ptx
      production. Under conditions that limited cysteine, a fivefold increase in Ptx
      production was observed. Addition of barium chloride (BaCl2) to the culture
      further increased Ptx yield. Our results suggest that B. pertussis is capable of
      autoregulating the activity of the bvg regulon through its metabolism of
      cysteine. Reduction of the amount of cysteine in the media results in prolonged
      vir expression due to the absence of the negative inhibitor SO4(2-). Therefore,
      the combined presence and metabolism of cysteine may be an important mechanism in
      the pathogenesis of B. pertussis.

PMID- 11598056
TI  - Identification of the hemolysis-associated protein 1 as a cross-protective
      immunogen of Leptospira interrogans by adenovirus-mediated vaccination.
AB  - New vaccine strategies are needed for the prevention of leptospirosis, a
      widespread human and animal disease caused by pathogenic leptospires. Our
      previous work determined that a protein leptospiral extract conferred cross
      protection in a gerbil model of leptospirosis. The 31- to 34-kDa protein fraction
      of Leptospira interrogans serovar autumnalis was shown sufficient for this
      purpose. In the present study, N-terminal sequencing of a 32-kDa fraction and
      Southern blotting of genomic DNA with corresponding degenerated oligonucleotide
      probes identified two of its constituents: hemolysis-associated protein 1 (Hap1)
      and the outer membrane Leptospira protein 1 (OmpL1). Adenovirus-mediated Hap1
      vaccination induces significant protection against a virulent heterologous
      Leptospira challenge in gerbils, whereas a similar OmpL1 construct failed to
      protect the animals. These data indicate that Hap1 could be a good candidate for
      developing a new generation of vaccines able to induce broad protection against
      leptospirosis disease.

PMID- 11598057
TI  - Cytotoxic necrotizing factor from Escherichia coli induces RhoA-dependent
      expression of the cyclooxygenase-2 Gene.
AB  - Cytotoxic necrotizing factor 1 (CNF) is a toxin produced by some isolates of
      Escherichia coli that cause extraintestinal infections. CNF can initiate
      signaling pathways that are mediated by the Rho family of small GTPases through a
      covalent modification that results in constitutive activation. In addition to
      regulating the assembly of actin stress fibers and focal adhesion complexes, RhoA
      can also regulate gene expression at the level of transcription. Here we
      demonstrate for the first time, by using a luciferase-based reporter system, that
      the transcription of cyclooxygenase-2 (COX-2) is strongly upregulated in NIH 3T3
      fibroblasts treated with CNF and that this effect is dependent upon the
      activation of RhoA by the toxin. Subsequent protein tyrosine phosphorylation
      events modulate the induction, but the transcription signal is not mediated by
      Rho-associated kinase (p160/ROCK) and so must rely upon another effector that is
      activated by RhoA. CNF therefore induces COX-2 expression via a RhoA-dependent
      signaling pathway that diverges from the pathway that regulates cytoskeletal
      rearrangements in response to RhoA activation.

PMID- 11598058
TI  - Comparison of genomic structures and antigenic reactivities of orthologous 29
      kilodalton outer membrane proteins of Helicobacter pylori.
AB  - We purified a 29-kDa Helicobacter pylori outer membrane protein (Omp29 protein)
      and cloned the gene encoding the protein from H. pylori strain ATCC 43504. The
      Omp29 gene corresponded to the reported JHP73 and the HP78-79 genes of H. pylori
      strains. A corresponding nucleotide fragment was detected in all 150 tested H.
      pylori clinical isolates by PCR or Southern blotting. The amplified Omp29
      corresponding fragments were categorized into a ca. 770-bp-long group and a
      larger-fragment group. Sequence analysis indicated that the larger fragments were
      likely synthesized from the 770-bp fragments by insertion of an irrelevant
      fragment via 17-bp-long repeat sequences. Immunoblot analysis implies that the
      ca. 770-bp fragment is responsible for the protein homologous to Omp29, whereas
      the larger fragments are not responsible for those proteins or encoding
      antigenically distinct proteins. We postulate that the H. pylori outer membrane
      protein Omp29 can alter its antigenicity through gene modifications mediated by
      nucleotide transfer.

PMID- 11598059
TI  - CD4(+) T lymphocytes from calves immunized with Anaplasma marginale major surface
      protein 1 (MSP1), a heteromeric complex of MSP1a and MSP1b, preferentially
      recognize the MSP1a carboxyl terminus that is conserved among strains.
AB  - Native major surface protein 1 (MSP1) of the ehrlichial pathogen Anaplasma
      marginale induces protective immunity in calves challenged with homologous and
      heterologous strains. MSP1 is a heteromeric complex of a single MSP1a protein
      covalently associated with MSP1b polypeptides, of which at least two (designated
      MSP1F1 and MSP1F3) in the Florida strain are expressed. Immunization with
      recombinant MSP1a and MSP1b alone or in combination fails to provide protection.
      The protective immunity in calves immunized with native MSP1 is associated with
      the development of opsonizing and neutralizing antibodies, but CD4(+) T
      lymphocyte responses have not been evaluated. CD4(+) T lymphocytes participate in
      protective immunity to ehrlichial pathogens through production of gamma
      interferon (IFN-gamma), which promotes switching to high-affinity immunoglobulin
      G (IgG) and activation of phagocytic cells to produce nitric oxide. Thus, an
      effective vaccine for A. marginale and related organisms should contain both T-
      and B-lymphocyte epitopes that induce a strong memory response that can be
      recalled upon challenge with homologous and heterologous strains. This study was
      designed to determine the relative contributions of MSP1a and MSP1b proteins,
      which contain both variant and conserved amino acid sequences, in stimulating
      memory CD4(+) T-lymphocyte responses in calves immunized with native MSP1.
      Peripheral blood mononuclear cells and CD4(+) T-cell lines from MSP1-immunized
      calves proliferated vigorously in response to the immunizing strain (Florida) and
      heterologous strains of A. marginale. The conserved MSP1-specific response was
      preferentially directed to the carboxyl-terminal region of MSP1a, which
      stimulated high levels of IFN-gamma production by CD4(+) T cells. In contrast,
      there was either weak or no recognition of MSP1b proteins. Paradoxically, all
      calves developed high titers of IgG antibodies to both MSP1a and MSP1b
      polypeptides. These findings suggest that in calves immunized with MSP1
      heteromeric complex, MSP1a-specific T lymphocytes may provide help to MSP1b
      specific B lymphocytes. The data provide a basis for determining whether selected
      MSP1a CD4(+) T-lymphocyte epitopes and selected MSP1a and MSP1b B-lymphocyte
      epitopes presented on the same molecule can stimulate a protective immune
      response.

PMID- 11598060
TI  - Identification and characterization of a novel genomic island integrated at selC
      in locus of enterocyte effacement-negative, Shiga toxin-producing Escherichia
      coli.
AB  - The selC tRNA gene is a common site for the insertion of pathogenicity islands in
      a variety of bacterial enteric pathogens. We demonstrate here that Escherichia
      coli that produces Shiga toxin 2d and does not harbor the locus of enterocyte
      effacement (LEE) contains, instead, a novel genomic island. In one representative
      strain (E. coli O91:H(-) strain 4797/97), this island is 33,014 bp long and, like
      LEE in E. coli O157:H7, is integrated 15 bp downstream of selC. This E. coli
      O91:H(-) island contains genes encoding a novel serine protease, termed EspI; an
      adherence-associated locus, similar to iha of E. coli O157:H7; an E. coli vitamin
      B12 receptor (BtuB); an AraC-type regulatory module; and four homologues of E.
      coli phosphotransferase proteins. The remaining sequence consists largely of
      complete and incomplete insertion sequences, prophage sequences, and an intact
      phage integrase gene that is located directly downstream of the chromosomal selC.
      Recombinant EspI demonstrates serine protease activity using pepsin A and human
      apolipoprotein A-I as substrates. We also detected Iha-reactive protein in outer
      membranes of a recombinant clone and 10 LEE-negative, Shiga toxin-producing E.
      coli (STEC) strains by immunoblot analysis. Using PCR analysis of various STEC,
      enteropathogenic E. coli, enterotoxigenic E. coli, enteroaggregative E. coli,
      uropathogenic E. coli, and enteroinvasive E. coli strains, we detected the iha
      homologue in 59 (62%) of 95 strains tested. In contrast, espI and btuB were
      present in only two (2%) and none of these strains, respectively. We conclude
      that the newly described island occurs exclusively in a subgroup of STEC strains
      that are eae negative and contain the variant stx(2d )gene.

PMID- 11598061
TI  - Involvement of fungal cell wall components in adhesion of Sporothrix schenckii to
      human fibronectin.
AB  - Systemic sporotrichosis is an emerging infection potentially fatal for
      immunocompromised patients. Adhesion to extracellular matrix proteins is thought
      to play a crucial role in invasive fungal diseases. Here we report studies of the
      adhesion of Sporothrix schenckii to the extracellular protein fibronectin (Fn).
      Both yeast cells and conidia of S. schenckii were able to adhere to Fn as
      detected by enzyme-linked immunosorbent binding assays. Adhesion of yeast cells
      to Fn is dose dependent and saturable. S. schenckii adheres equally well to 40
      kDa and 120-kDa Fn proteolytic fragments. While adhesion to Fn was increased by
      Ca(2+), inhibition assays demonstrated that it was not RGD dependent. A
      carbohydrate-containing cell wall neutral fraction blocked up to 30% of the
      observed adherence for the yeast cells. The biochemical nature of this fraction
      suggests the participation of cell surface glycoconjugates in binding by their
      carbohydrate or peptide moieties. These results provide new data concerning S.
      schenckii adhesion mechanisms, which could be important in host-fungus
      interactions and the establishment of sporotrichosis.

PMID- 11598062
TI  - Effect of deficiency of tumor necrosis factor alpha or both of its receptors on
      Streptococcus pneumoniae central nervous system infection and peritonitis.
AB  - Tumor necrosis factor alpha (TNF-alpha) and TNF-beta are key mediators in
      bacterial inflammation. We therefore examined the role of TNF-alpha and its two
      receptors in murine pneumococcal central nervous system infection. TNF-alpha
      knockout mice and age- and sex-matched controls and TNF receptor (p55 and p75)
      deficient mice and heterozygous littermates were infected intracerebrally with a
      Streptococcus pneumoniae type 3 strain. Mice were monitored until death or were
      killed 36 h after infection. Bacterial titers in blood, spleen, and brain
      homogenates were determined. Leukocyte infiltration and neuronal damage were
      assessed by histological scores. TNF-alpha-deficient mice died earlier than the
      controls after intracerebral infection although overall survival was similar. TNF
      alpha deficiency did not inhibit leukocyte recruitment into the subarachnoid
      space and did not lead to an increased density of bacteria in brain homogenates.
      However, it caused a substantial rise of the concentration of S. pneumoniae cells
      in blood and spleen. Spleen bacterial titers were also increased in p55- and p75
      deficient mice. TNF receptor-deficient mice showed decreased meningeal
      inflammation. Neuronal damage was not affected by either TNF-alpha or TNF
      receptor deficiency. In a murine model of pneumococcal peritonitis, 10(2) CFU of
      S. pneumoniae produced fatal peritonitis in TNF-alpha-deficient, but not wild
      type, mice. Early leukocyte influx into the peritoneum was impaired in TNF-alpha
      deficient mice. The lack of TNF-alpha or its receptors renders mice more
      susceptible to S. pneumoniae infections.

PMID- 11598063
TI  - Determination of the infectious dose of Helicobacter pylori during primary and
      secondary infection in rhesus monkeys (Macaca mulatta).
AB  - We sought to determine the infectious dose of Helicobacter pylori during primary
      and secondary infection in the rhesus monkey and to determine whether
      preinoculation acid suppression is necessary to produce colonization. Mixed
      inoculation with three human-derived strains showed that H. pylori J166 is
      particularly adapted to colonization of rhesus monkeys, since it outcompeted two
      other strains. The minimum infectious dose of H. pylori J166 was 10(4) bacteria
      in specific-pathogen (H. pylori)-free monkeys. Rechallenge of these monkeys after
      antibiotic therapy was characterized by a 10- to 100-fold decrease in bacterial
      load compared to primary infection, but with little change in the infectious
      dose. Acid suppression prior to inoculation was not necessary for colonization to
      occur. These results provide a basis for future animal experiments using more
      ecologically relevant conditions of inoculation and suggest that reduction in
      bacterial load rather than complete protection may be a more realistic goal for
      H. pylori vaccination.

PMID- 11598064
TI  - Identification of a group 1-like capsular polysaccharide operon for Vibrio
      vulnificus.
AB  - Virulence of Vibrio vulnificus correlates with changes in colony morphology that
      are indicative of a reversible phase variation for expression of capsular
      polysaccharide (CPS). Encapsulated variants are virulent with opaque colonies,
      whereas phase variants with reduced CPS expression are attenuated and are
      translucent. Using TnphoA mutagenesis, we identified a V. vulnificus CPS locus,
      which included an upstream ops element, a wza gene (wza(Vv)), and several open
      reading frames with homology to CPS biosynthetic genes. This genetic organization
      is characteristic of group 1 CPS operons. The wza gene product is required for
      transport of CPS to the cell surface in Escherichia coli. Polar transposon
      mutations in wza(Vv) eliminated expression of downstream biosynthetic genes,
      confirming operon structure. On the other hand, nonpolar inactivation of wza(Vv)
      was specific for CPS transport, did not alter CPS biosynthesis, and could be
      complemented in trans. Southern analysis of CPS phase variants revealed deletions
      or rearrangements at this locus. A survey of environmental isolates indicated a
      correlation between deletions in wza(Vv) and loss of virulent phenotype,
      suggesting a genetic mechanism for CPS phase variation. Full virulence in mice
      required surface expression of CPS and supported the essential role of capsule in
      the pathogenesis of V. vulnificus.

PMID- 11598065
TI  - Diminished virulence of an alpha-toxin mutant of Staphylococcus aureus in
      experimental brain abscesses.
AB  - Staphylococcus aureus is one of the major etiologic agents of brain abscesses in
      humans, occasionally leading to focal neurological deficits and even death. The
      objective of the present study was to identify key virulence determinants
      contributing to the pathogenesis of S. aureus in the brain using a murine brain
      abscess model. The importance of virulence factor production in disease
      development was demonstrated by the inability of heat-inactivated S. aureus to
      induce proinflammatory cytokine or chemokine expression or brain abscess
      formation in vivo. To directly address the contribution of virulence determinants
      in brain abscess development, the abilities of S. aureus strains with mutations
      in the global regulatory loci sarA and agr were examined. An S. aureus sarA agr
      double mutant exhibited reduced virulence in vivo, as demonstrated by attenuated
      proinflammatory cytokine and chemokine expression and bacterial replication.
      Subsequent studies focused on the expression of factors that are altered in the
      sarA agr double mutant. Evaluation of an alpha-toxin mutant revealed a phenotype
      similar to that of the sarA agr mutant in vivo, as evidenced by lower bacterial
      burdens and attenuation of cytokine and chemokine expression in the brain. This
      suggested that alpha-toxin is a central virulence determinant in brain abscess
      development. Another virulence mechanism utilized by staphylococci is
      intracellular survival. Cells recovered from brain abscesses were shown to harbor
      S. aureus intracellularly, providing a means by which the organism may establish
      chronic infections in the brain. Together, these data identify alpha-toxin as a
      key virulence determinant for the survival of S. aureus in the brain.

PMID- 11598066
TI  - Interaction of Neisseria meningitidis with human dendritic cells.
AB  - Infection with Neisseria meningitidis serogroup B is responsible for fatal
      septicemia and meningococcal meningitis. The severity of disease directly
      correlates with the production of the proinflammatory cytokines tumor necrosis
      factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, and IL-8. However, the
      source of these cytokines has not been clearly defined yet. Since bacterial
      infection involves the activation of dendritic cells (DCs), we analyzed the
      interaction of N. meningitidis with monocyte-derived DCs. Using N. meningitidis
      serogroup B wild-type and unencapsulated bacteria, we found that capsule
      expression significantly impaired neisserial adherence to DCs. In addition,
      phagocytic killing of the bacteria in the phagosome is reduced by at least 10- to
      100-fold. However, all strains induced strong secretion of proinflammatory
      cytokines TNF-alpha, IL-6, and IL-8 by DCs (at least 1,000-fold at 20 h
      postinfection [p.i.]), with significantly increased cytokine levels being
      measurable by as early as 6 h p.i. Levels of IL-1beta, in contrast, were
      increased only 200- to 400-fold at 20 h p.i. with barely measurable induction at
      6 h p.i. Moreover, comparable amounts of cytokines were induced by bacterium-free
      supernatants of Neisseria cultures containing neisserial lipooligosaccharide as
      the main factor. Our data suggest that activated DCs may be a significant source
      of high levels of proinflammatory cytokines in neisserial infection and thereby
      may contribute to the pathology of meningococcal disease.

PMID- 11598067
TI  - Sequence analysis of four Shigella boydii O-antigen loci: implication for
      Escherichia coli and Shigella relationships.
AB  - Shigella strains are in reality clones of Escherichia coli and are believed to
      have emerged relatively recently (G. M. Pupo, R. Lan, and P. R. Reeves, Proc.
      Natl. Acad. Sci. USA 97:10567-10572, 2000). There are 33 O-antigen forms in these
      Shigella clones, of which 12 are identical to O antigens of other E. coli
      strains. We sequenced O-antigen gene clusters from Shigella boydii serotypes 4,
      5, 6, and 9 and also studied the O53- and O79-antigen gene clusters of E. coli,
      encoding O antigens identical to those of S. boydii serotype 4 and S. boydii
      serotype 5, respectively. In both cases the S. boydii and E. coli O-antigen gene
      clusters have the same genes and organization. The clusters of both S. boydii 6
      and S. boydii 9 O antigens have atypical features, with a functional insertion
      sequence and a wzx gene located in the orientation opposite to that of all other
      genes in S. boydii serotype 9 and an rmlC gene located away from other rml genes
      in S. boydii serotype 6. Sequences of O-antigen gene clusters from another three
      Shigella clones have been published, and two of them also have abnormal
      structures, with either the entire cluster or one gene being located on a plasmid
      in Shigella sonnei or Shigella dysenteriae, respectively. It appears that a high
      proportion of clusters coding for O antigens specific to Shigella clones have
      atypical features, perhaps indicating recent formation of these gene clusters.

PMID- 11598068
TI  - Cloning of the Streptococcus mutans gene encoding glucan binding protein B and
      analysis of genetic diversity and protein production in clinical isolates.
AB  - Streptococcus mutans, the primary etiological agent of dental caries, produces
      several activities that promote its accumulation within the dental biofilm. These
      include glucosyltransferases, their glucan products, and proteins that bind
      glucan. At least three glucan binding proteins have been identified, and GbpB,
      the protein characterized in this study, appears to be novel. The gbpB gene was
      cloned and the predicted protein sequence contained several unusual features and
      shared extensive homology with a putative peptidoglycan hydrolase from group B
      streptococcus. Examination of gbpB genes from clinical isolates of S. mutans
      revealed that DNA polymorphisms, and hence amino acid changes, were limited to
      the central region of the gene, suggesting functional conservation within the
      amino and carboxy termini of the protein. The GbpB produced by clinical isolates
      and laboratory strains showed various distributions between cells and culture
      medium, and amounts of protein produced by individual strains correlated
      positively with their ability to grow as biofilms in an in vitro assay.

PMID- 11598069
TI  - Dual role of lipopolysaccharide (LPS)-binding protein in neutralization of LPS
      and enhancement of LPS-induced activation of mononuclear cells.
AB  - The lipopolysaccharide (LPS)-binding protein (LBP) has a concentration-dependent
      dual role in the pathogenesis of gram-negative sepsis: low concentrations of LBP
      enhance the LPS-induced activation of mononuclear cells (MNC), whereas the acute
      phase rise in LBP concentrations inhibits LPS-induced cellular stimulation. In
      stimulation experiments, we have found that LBP mediates the LPS-induced cytokine
      release from MNC even under serum-free conditions. In biophysical experiments we
      demonstrated that LBP binds and intercalates into lipid membranes, amplified by
      negative charges of the latter, and that intercalated LBP can mediate the CD14
      independent intercalation of LPS into membranes in a lipid-specific and
      temperature-dependent manner. In contrast, prior complexation of LBP and LPS
      inhibited binding of these complexes to membranes due to different binding of LBP
      to LPS or phospholipids. This results in a neutralization of LPS and, therefore,
      to a reduced production of tumor necrosis factor by MNC. We propose that LBP is
      not only present as a soluble protein in the serum but may also be incorporated
      as a transmembrane protein in the cytoplasmic membrane of MNC and that the
      interaction of LPS with membrane-associated LBP may be an important step in LBP
      mediated activation of MNC, whereas LBP-LPS complexation in the serum leads to a
      neutralization of LPS.

PMID- 11598070
TI  - Heme utilization in Bordetella avium is regulated by RhuI, a heme-responsive
      extracytoplasmic function sigma factor.
AB  - Efficient utilization of heme as an iron (Fe) source by Bordetella avium requires
      bhuR, an Fe-regulated gene which encodes an outer membrane heme receptor.
      Upstream of bhuR is a 507-bp open reading frame, hereby designated rhuI (for
      regulator of heme uptake), which codes for a 19-kDa polypeptide. Whereas the 19
      kDa polypeptide had homology to a subfamily of alternative sigma factors known as
      the extracytoplasmic function (ECF) sigma factors, it was hypothesized that rhuI
      encoded a potential in-trans regulator of the heme receptor gene in trans.
      Support for the model was strengthened by the identification of nucleotide
      sequences common to ECF sigma-dependent promoters in the region immediately
      upstream of bhuR. Experimental evidence for the regulatory activities of rhuI was
      first revealed by recombinant experiments in which overproduction of rhuI was
      correlated with a dramatically increased expression of BhuR. A putative rhuI
      dependent bhuR promoter was identified in the 199-bp region located proximal to
      bhuR. When a transcriptional fusion of the 199-bp region and a promoterless lacZ
      gene was introduced into Escherichia coli, promoter activity was evident, but
      only when rhuI was coexpressed in the cell. Sigma competition experiments in E.
      coli demonstrated that rhuI conferred biological properties on the cell that were
      consistent with RhuI having sigma factor activity. Heme, hemoglobin, and several
      other heme-containing proteins were shown to be the extracellular inducers of the
      rhuI-dependent regulatory system. Fur titration assays indicated that expression
      of rhuI was probably Fur dependent.

PMID- 11598071
TI  - Dual-function vaccine for Pseudomonas aeruginosa: characterization of chimeric
      exotoxin A-pilin protein.
AB  - Pseudomonas aeruginosa is the major infectious agent of concern for cystic
      fibrosis patients. Strategies to prevent colonization by this bacterium and/or
      neutralize its virulence factors are clearly needed. Here we characterize a dual
      function vaccine designed to generate antibodies to reduce bacterial adherence
      and to neutralize the cytotoxic activity of exotoxin A. To construct the vaccine,
      key sequences from type IV pilin were inserted into a vector encoding a nontoxic
      (active-site deletion) version of exotoxin A. The chimeric protein, termed
      PE64Delta553pil, was expressed in Escherichia coli, refolded to a near-native
      conformation, and then characterized by various biochemical and immunological
      assays. PE64Delta553pil bound specifically to asialo-GM1, and, when injected into
      rabbits, produced antibodies that reduced bacterial adherence and neutralized the
      cell-killing activity of exotoxin A. Results support further evaluation of this
      chimeric protein as a vaccine to prevent Pseudomonas colonization in susceptible
      individuals.

PMID- 11598072
TI  - cDNA array analysis of cag pathogenicity island-associated Helicobacter pylori
      epithelial cell response genes.
AB  - Helicobacter pylori strains containing the cag pathogenicity island (PAI) induce
      NF-kappaB activation and interleukin-8 secretion in gastric epithelial cells. The
      aim of this study was to investigate changes in epithelial gene expression
      induced by cag PAI-positive and -negative strains of H. pylori using high-density
      cDNA array hybridization technology. Radio-labeled cDNA prepared from H. pylori
      infected Kato 3 gastric epithelial cells was hybridized to high-density cDNA
      arrays to identify changes in epithelial gene expression compared to noninfected
      controls. In vivo expression of selected, differentially expressed genes was
      examined by reverse transcription-PCR analysis of H. pylori-positive and 
      negative gastric mucosa. Screening of ca. 57,800 cDNAs identified 208 known genes
      and 48 novel genes and/or expressed sequence tags of unknown function to be
      differentially expressed in Kato 3 cells following H. pylori infection. Marked
      differences in gene expression profiles were observed following cag PAI-positive
      and cag PAI-negative infection with 15 novel cDNAs and 92 known genes being
      differentially expressed. H. pylori was found to change the expression of genes
      encoding growth factors and cytokine/chemokines and their receptors, apoptosis
      proteins, transcription factors and metalloprotease-disintegrin proteins (ADAMs),
      and tissue inhibitors of metalloproteinases. Gastric differential expression of
      selected known genes (amphiregulin and ADAM 10) and a novel gene (HPYR1) was
      confirmed in vivo in patients with H. pylori infection. Confirmation of the in
      vivo expression of selected genes demonstrates the usefulness of this approach
      for investigating pathogen-induced changes in host gene expression.

PMID- 11598073
TI  - Reciprocal protective immunity against Bordetella pertussis and Bordetella
      parapertussis in a murine model of respiratory infection.
AB  - The protective immunity induced by infection with Bordetella pertussis and with
      Bordetella parapertussis was examined in a murine model of respiratory infection.
      Convalescent mice that had been infected by aerosol with B. pertussis or with B.
      parapertussis exhibited a protective immune response against B. pertussis and
      also against B. parapertussis. Anti-filamentous hemagglutinin (anti-FHA) serum
      immunoglobulin G (IgG) and anti-FHA lung IgA antibodies were detected in both
      mice infected with B. pertussis and those infected with B. parapertussis.
      Antibodies against pertussis toxin (anti-PT) and against killed B. pertussis
      cells were detected in mice infected with B. pertussis. Pertactin-specific
      antibodies and antibodies against killed B. parapertussis cells were detected in
      mice infected with B. parapertussis. Spleen cells from mice infected with B.
      pertussis secreted interferon-gamma (IFN-gamma) in response to stimulation by FHA
      or PT. Spleen cells from mice infected with B. parapertussis also secreted IFN
      gamma in response to FHA. Interleukin-4 was not produced in response to any of
      the antigens tested. The profiles of cytokine secretion in vitro revealed
      induction of a Th1-biased immune response during convalescence from infection by
      B. pertussis and by B. parapertussis. It is possible that Th1 and Th2 responses
      against FHA might be related to the reciprocal protection achieved in our murine
      model.

PMID- 11598074
TI  - A 60-kilodalton immunodominant glycoprotein is essential for cell wall integrity
      and the maintenance of cell shape in Streptococcus mutans.
AB  - We have demonstrated previously by Western blotting that in naturally sensitized
      humans, the serum or salivary antibody response to Streptococcus mutans was
      directed predominantly to a protein antigen with a size of approximately 60-kDa.
      To identify this immunodominant antigen, specific serum antibodies were eluted
      from immunoblots and five positive clones with inserts ranging in length from 3
      to 8 kb from identical chromosomal loci were obtained by screening a genomic
      expression library of Streptococcus mutans GS-5. Amino acid sequencing
      established the identity of this immunodominant antigen, a 60-kDa immunodominant
      glycoprotein (IDG-60), to be a cell wall-associated general stress protein GSP
      781, which was originally predicted to have a molecular mass of approximately 45
      kDa based on the derived nucleotide sequence. Discrepancy in the molecular mass
      was also observed in recombinant his-tagged IDG-60 (rIDG-60) expressed from
      Escherichia coli. Glycosylation, consisting of sialic acid, mannose galactose,
      and N-acetylgalactosamine, was detected by lectin binding to IDG-60 in cell wall
      extracts from S. mutans and rIDG-60 expressed in vivo or translated in vitro.
      Despite the presence of multiple Asn or Ser or Thr glycosylation sites, IDG-60
      was resistant to the effect of N-glycosidase F and multiple O-glycosidase
      molecules but not to beta-galactosidase. Insertional inactivation of the gene
      encoding IDG-60, sagA, resulted in a retarded growth rate, destabilization of the
      cell wall, and pleiomorphic cell shape with multifold ingrowth of cell wall. In
      addition, distinct from the parental GS-5 strain, the isogenic mutant GS-51 was
      unable to survive the challenge of low pH and high osmotic pressure or high
      temperature. Expression of the wild-type gene in trans within GS-51 from plasmid
      pDL277 complemented the growth defect and restored normal cell shape. These
      results suggested that IDG-60 is essential for maintaining the integrity of the
      cell wall and the uniformity of cell shape, both of which are indispensable for
      bacteria survival under stress conditions.

PMID- 11598075
TI  - Characterization of Saa, a novel autoagglutinating adhesin produced by locus of
      enterocyte effacement-negative Shiga-toxigenic Escherichia coli strains that are
      virulent for humans.
AB  - The capacity of Shiga toxigenic Escherichia coli (STEC) to adhere to the
      intestinal mucosa undoubtedly contributes to pathogenesis of human disease. The
      majority of STEC strains isolated from severe cases produce attaching and
      effacing lesions on the intestinal mucosa, a property mediated by the locus of
      enterocyte effacement (LEE) pathogenicity island. This element is not essential
      for pathogenesis, as some cases of severe disease, including hemolytic uremic
      syndrome (HUS), are caused by LEE-negative STEC strains, but the mechanism
      whereby these adhere to the intestinal mucosa is not understood. We have isolated
      a gene from the megaplasmid of a LEE-negative O113:H21 STEC strain (98NK2)
      responsible for an outbreak of HUS, which encodes an auto-agglutinating adhesin
      designated Saa (STEC autoagglutinating adhesin). Introduction of saa cloned in
      pBC results in a 9.7-fold increase in adherence of E. coli JM109 to HEp-2 cells
      and a semilocalized adherence pattern. Mutagenesis of saa in 98NK2, or curing the
      wild-type strain of its megaplasmid, resulted in a significant reduction in
      adherence. Homologues of saa were found in several unrelated LEE-negative STEC
      serotypes, including O48:H21 (strain 94CR) and O91:H21 (strain B2F1), which were
      also isolated from patients with HUS. Saa exhibits a low degree of similarity
      (25% amino acid [aa] identity) with YadA of Yersinia enterocolitica and Eib, a
      recently described phage-encoded immunoglobulin binding protein from E. coli. Saa
      produced by 98NK2 is 516 aa long and includes four copies of a 37-aa direct
      repeat sequence. Interestingly, Saa produced by other STEC strains ranges in size
      from 460 to 534 aa as a consequence of variation in the number of repeats and/or
      other insertions or deletions immediately proximal to the repeat domain.

PMID- 11598076
TI  - Analysis of pilus adhesins from Haemophilus influenzae biotype IV strains.
AB  - A subset of nontypeable Haemophilus influenzae (NTHI) biotype IV isolates from
      the human genital tract or from infected newborn infants forms a cryptic
      genospecies characterized by, among other features, the presence of peritrichous
      pili. The objective of this study was to determine the similarity of these pili
      to hemagglutinating, HifA- and HifE-containing pili expressed by respiratory H.
      influenzae isolates. For this analysis, the presence of hifA and hifE and their
      gene products in NTHI biotype IV strains was assessed, the binding of H.
      influenzae biotype IV strains to human epithelial cells was characterized,
      possible genital tissue tropism of these isolates was explored, and the role of
      HifA- and HifE-possessing pili in the adhesion of NTHI biotype IV strains to
      human epithelial cells was determined. None of the six biotype IV NTHI isolates
      tested agglutinated human red blood cells, nor could they be enriched for
      hemagglutinating variants. Although hifA, which encodes the major structural
      subunit of hemagglutinating pili, and hifE, which encodes the tip adhesin of
      hemagglutinating pili, were detected by PCR from six and five, respectively, of
      the six biotype IV strains tested, neither HifA nor HifE (the gene products of
      hifA and hifE) were detected in any of these strains by Western blot analysis
      using antisera that recognize HifA and HifE of respiratory strains. Transmission
      electron microscopy showed no surface pili on the two biotype IV H. influenzae
      isolates examined; strain 4162 containing an insertional mutation in hifA also
      showed no surface pili, whereas strain 1595 containing an insertional mutation in
      hifB showed pilus-like structures that were shorter and thicker than
      hemagglutinating pili of the respiratory strains AAr176 and M43. In enzyme-linked
      immunosorbent assays, biotype IV strains adhered to 16HBE14o(-) and HEp-2 cells
      of respiratory origin as well as to ME180 and HeLa cells of genital origin. This
      adherence was not pilus specific, however, as GM-1, a known pilus receptor
      analog, did not inhibit binding of biotype IV strains to ME180, HEp-2, or HeLa
      cells, and GM-1 inhibition of binding to 16HBE14o(-) cells did not correlate with
      the presence of hifE. While both nonpiliated variants and hifA and hifB (encoding
      the pilus chaperone) mutants of respiratory strain AAr176 showed reduced binding
      (64 to 87% of that of piliated AAr176) to 16HBE14o(-) and ME180 cells, hifA and
      hifB mutants of the biotype IV strains showed minimal reduction in binding to
      these cell lines (91 to 98% of that of wild-type strains). Thus, although biotype
      IV H. influenzae isolates of the cryptic genospecies possess the genes that code
      for HifA- and HifE-containing hemagglutinating pili, epithelial cell adherence
      exhibited by these strains is not mediated by expression of hemagglutinating
      pili.

PMID- 11598077
TI  - Minor nucleotide substitutions in the omp31 gene of Brucella ovis result in
      antigenic differences in the major outer membrane protein that it encodes
      compared to those of the other Brucella species.
AB  - The gene coding for the major outer membrane protein Omp31 was sequenced in five
      Brucella species and their biovars. Although the omp31 genes appeared to be
      highly conserved in the genus Brucella, nine nucleotide substitutions were
      detected in the gene of Brucella ovis compared to that of Brucella melitensis. As
      shown by differential binding properties of monoclonal antibodies (MAbs) to the
      two Brucella species, these nucleotide substitutions result in different
      antigenic properties of Omp31. The antigenic differences were also evidenced when
      sera from B. ovis-infected rams were tested by Western blotting with the
      recombinant B. melitensis or B. ovis Omp31 proteins. Twelve available sera
      reacted with recombinant B. ovis Omp31, but only four of them reacted with
      recombinant B. melitensis Omp31. These results validate previous evidence for the
      potential of Omp31 as a diagnostic antigen for B. ovis infection in rams and
      demonstrate that B. ovis Omp31, instead of B. melitensis Omp31, should be used to
      evaluate this point. The antigenic differences between the B. melitensis and B.
      ovis Omp31 proteins should also be taken into account when Omp31 is evaluated as
      a candidate for the development of subcellular vaccines against B. ovis
      infection. No reactivity against recombinant B. melitensis Omp31 was detected, by
      Western blotting, with sera from B. melitensis-infected sheep. Accordingly, Omp31
      does not seem to be a good diagnostic antigen for B. melitensis infections in
      sheep. Two immunodominant regions were identified on the B. ovis Omp31 protein by
      using recombinant DNA techniques and specific MAbs. Sera from B. ovis-infected
      rams that reacted with the recombinant protein were tested by Western blotting
      against one of these immunodominant regions shown to be exposed at the bacterial
      surface. Only 4 of the 12 sera reacted, but with strong intensity.

PMID- 11598078
TI  - Generation and surface localization of intact M protein in Streptococcus pyogenes
      are dependent on sagA.
AB  - The M protein is an important surface-located virulence factor of Streptococcus
      pyogenes, the group A streptococcus (GAS). Expression of M protein is primarily
      controlled by Mga, a transcriptional activator protein. A recent report suggested
      that the sag locus, which includes nine genes necessary and sufficient for
      production of streptolysin S, another GAS virulence factor, is also needed for
      transcription of emm, encoding the M protein (Z. Li, D. D. Sledjeski, B.
      Kreikemeyer, A. Podbielski, and M. D. Boyle, J. Bacteriol. 181:6019-6027, 1999).
      To investigate this in more detail, we constructed an insertion-deletion mutation
      in sagA, the first gene in the sag locus, in the M6 strain JRS4. The resulting
      strain, JRS470, produced no detectable streptolysin S and showed a drastic
      reduction in cell surface-associated M protein, as measured by cell aggregation
      and Western blot analysis. However, transcription of the emm gene was unaffected
      by the sagA mutation. Detailed analysis with monoclonal antibodies and an
      antipeptide antibody showed that the M protein in the sagA mutant strain was
      truncated so that it lacks the C-repeat region and the C-terminal domain required
      for anchoring it to the cell surface. This truncated M protein was largely found,
      as expected, in the culture supernatant. Lack of surface-located M protein made
      the sagA mutant strain susceptible to phagocytosis. Thus, although sagA does not
      affect transcription of the M6 protein gene, it is needed for the surface
      localization of this important virulence factor.

PMID- 11598079
TI  - Survival of Chlamydia pneumoniae-infected Mono Mac 6 cells is dependent on NF
      kappaB binding activity.
AB  - The respiratory tract pathogen Chlamydia pneumoniae has been associated with
      atherosclerosis. Monocytes are supposed to serve as a vehicle for systemic
      dissemination of intracellular C. pneumoniae from the lung to the artery vessel
      wall. We were therefore interested in pathogen-induced cellular events associated
      with NF-kappaB, a crucial transcription factor for both inflammatory cytokines
      and antiapoptotic molecules. In this study we demonstrate by electrophoretic
      mobility shift assay that C. pneumoniae infection of the human monocytic cell
      line Mono Mac 6 induces activation of NF-kappaB over 48 h, with a maximum level
      at 1 h postinfection. As shown by supershift assay, the activated NF-kappaB
      complex consists of the subunits RelA (p65) and NF-kappaB1 (p50). Apoptotic host
      cells were not detected during the early stages of the infection when maximal
      activation of NF-kappaB was detected. Pretreatment of Mono Mac 6 with the
      antioxidant and NF-kappaB inhibitor PDTC (pyrrolidine dithiocarbamate) induced
      activation of caspase-3 and led to apoptotic cell death. The C. pneumoniae
      induced activation of the NF-kappaB complex was reduced by PDTC, which in
      parallel resulted in an increased apoptosis, as quantified by annexin V labeling
      and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling
      reaction. In the complete absence of activated NF-kappaB, when Mono Mac 6 cells
      were pretreated with the more potent NF-kappaB inhibitors MG-132 and parthenolide
      a C. pneumoniae-mediated rescue of cells from induced apoptosis could not be
      achieved. Our results indicate that activation of NF-kappaB in C. pneumoniae
      infected Mono Mac 6 cells is associated with protection of Mono Mac 6 cells
      against apoptosis and might thereby contribute to systemic spread of the
      pathogen.

PMID- 11598080
TI  - Role of Streptococcus gordonii amylase-binding protein A in adhesion to
      hydroxyapatite, starch metabolism, and biofilm formation.
AB  - Interactions between bacteria and salivary components are thought to be important
      in the establishment and ecology of the oral microflora. alpha-Amylase, the
      predominant salivary enzyme in humans, binds to Streptococcus gordonii, a primary
      colonizer of the tooth. Previous studies have implicated this interaction in
      adhesion of the bacteria to salivary pellicles, catabolism of dietary starches,
      and biofilm formation. Amylase binding is mediated at least in part by the
      amylase-binding protein A (AbpA). To study the function of this protein, an
      erythromycin resistance determinant [erm(AM)] was inserted within the abpA gene
      of S. gordonii strains Challis and FAS4 by allelic exchange, resulting in abpA
      mutant strains Challis-E1 and FAS4-E1. Comparison of the wild-type and mutant
      strains did not reveal any significant differences in colony morphology,
      biochemical metabolic profiles, growth in complex or defined media, surface
      hydrophobicity, or coaggregation properties. Scatchard analysis of adhesion
      isotherms demonstrated that the wild-type strains adhered better to human parotid
      saliva- and amylase-coated hydroxyapatite than did the AbpA mutants. In contrast,
      the mutant strains bound to whole-saliva-coated hydroxyapatite to a greater
      extent than did the wild-type strains. While the wild-type strains preincubated
      with purified salivary amylase grew well in defined medium with potato starch as
      the sole carbohydrate source, the AbpA mutants did not grow under the same
      conditions even after preincubation with amylase. In addition, the wild-type
      strain produced large microcolonies in a flow cell biofilm model, while the abpA
      mutant strains grew much more poorly and produced relatively small microcolonies.
      Taken together, these results suggest that AbpA of S. gordonii functions as an
      adhesin to amylase-coated hydroxyapatite, in salivary-amylase-mediated catabolism
      of dietary starches and in human saliva-supported biofilm formation by S.
      gordonii.

PMID- 11598081
TI  - Developmental expression of two spore wall proteins during maturation of the
      microsporidian Encephalitozoon intestinalis.
AB  - Microsporidia are intracellular eukaryotes that infect many animals and cause
      opportunistic infections in AIDS patients. The disease is transmitted via
      environmentally resistant spores. Two spore wall constituents from the
      microsporidian Encephalitozoon intestinalis were characterized. Spore wall
      protein 1 (SWP1), a 50-kDa glycoprotein recognized by monoclonal antibody (MAb)
      11B2, was detected in developing sporonts and at low levels on the surfaces of
      mature spores. In contrast, SWP2, a 150-kDa glycoprotein recognized by MAb 7G7,
      was detected on fully formed sporonts and was more abundant on mature spores than
      SWP1. Nevertheless, the SWPs appeared to be complexed on the surfaces of mature
      spores. SWP1 and SWP2 are similar at the DNA and protein levels and have 10
      conserved cysteines in the N-terminal domain, suggesting similar secondary
      structures. The C-terminal domain of SWP2 has a unique region containing 50
      repeating 12- or 15-amino-acid units that lacks homology to known protein motifs.
      Antibodies from mice infected with E. intestinalis recognized SWP1 and SWP2. The
      characterization of two immunogenic SWPs from E. intestinalis will allow the
      study of exospore structure and function and may lead to the development of
      useful tools in the diagnosis and treatment of microsporidiosis.

PMID- 11598082
TI  - B-cell deficiency suppresses vaccine-induced protection against murine filariasis
      but does not increase the recovery rate for primary infection.
AB  - To establish the role of B cells and antibodies in destroying filariae, mice
      lacking mature B cells and therefore unable to produce antibodies were used.
      Litomosoides sigmodontis offers a good opportunity for this study because it is
      the only filarial species that completes its life cycle in mice. Its development
      was compared in B-cell-deficient mice (BALB/c muMT mice) and wild-type BALB/c
      mice in two different in vivo situations, vaccination with irradiated larvae and
      primary infection. In all cases, mice were challenged with subcutaneous
      inoculation of 40 infective larvae. Vaccine-induced protection was suppressed in
      B-cell-deficient mice. In these mice, eosinophils infiltrated the subcutaneous
      tissue normally during immunization; however, their morphological state did not
      change following challenge inoculation, whereas in wild-type mice the percentage
      of degranulated eosinophils was markedly increased. From this, it may be deduced
      that the eosinophil-antibody-B-cell complex is the effector mechanism of
      protection in vaccinated mice and that its action is fast and takes place in the
      subcutaneous tissue. In primary infection, the filarial survival and growth was
      not modified by the absence of B cells. However, no female worm had uterine
      microfilariae, nor did any mice develop a patent infection. In these mice,
      concentrations of type 1 (gamma interferon) and type 2 (interleukin-4 [IL-4], IL
      5 and IL-10) cytokines in serum were lower and pleural neutrophils were more
      numerous. The effects of the muMT mutation therefore differ from those in B1-cell
      deficient mice described on the same BALB/c background, which reveal a higher
      filarial recovery rate and microfilaremia. This outlines B2-cell-dependent
      mechanisms as favorable to the late maturation of L. sigmodontis.

PMID- 11598083
TI  - agr expression precedes escape of internalized Staphylococcus aureus from the
      host endosome.
AB  - Staphylococcus aureus is a versatile pathogen capable of causing life-threatening
      infections. Many of its cell wall and exoproduct virulence determinants are
      controlled via the accessory gene regulator (agr). Although considered primarily
      as an extracellular pathogen, it is now recognized that S. aureus can be
      internalized by epithelial and endothelial cells. Traditional experimental
      approaches to investigate bacterial internalization are extremely time-consuming
      and notoriously irreproducible. We present here a new reporter gene method to
      assess intracellular growth of S. aureus in MAC-T cells that utilizes a gfp
      luxABCDE reporter operon under the control of the Bacillus megaterium xylA
      promoter, which in S. aureus is expressed in a growth-dependent manner. This
      facilitates assessment of the growth of internalized bacteria in a nondestructive
      assay. The dual gfp-lux reporter cassette was also evaluated as a reporter of agr
      expression and used to monitor the temporal induction of agr during the MAC-T
      internalization process. The data obtained suggest that agr induction occurs
      prior to endosomal lysis and that agr-regulated exoproteins appear to be required
      prior to the release and replication of S. aureus within the infected MAC-T
      cells.

PMID- 11598084
TI  - Analysis of Borrelia burgdorferi vlsE gene expression and recombination in the
      tick vector.
AB  - Expression and recombination of the antigenic variation vlsE gene of the Lyme
      disease spirochete Borrelia burgdorferi were analyzed in the tick vector. To
      assess vlsE expression, Ixodes scapularis nymphs infected with the B. burgdorferi
      strain B31 were fed on mice for 48 or 96 h or to repletion and then crushed and
      acetone fixed either immediately thereafter (ticks collected at the two earlier
      time points) or 4 days after repletion. Unfed nymphs also were examined. At all
      of the time points investigated, spirochetes were able to bind a rabbit antibody
      raised against the conserved invariable region 6 of VlsE, as assessed by indirect
      immunofluorescence, but not preimmune serum from the same rabbit. This same
      antibody also bound to B31 spirochetes cultivated in vitro. Intensity of
      fluorescence appeared highest in cultured spirochetes, followed by spirochetes
      present in unfed ticks. Only a dim fluorescent signal was observed on spirochetes
      at the 48 and 96 h time points and at day 4 postrepletion. Expression of vlsE in
      vitro was affected by a rise in pH from 7.0 to 8.0 at 34 degrees C. Hence, vlsE
      expression appears to be sensitive to environmental cues of the type found in the
      B. burgdorferi natural history. To assess vlsE recombination, nymphs were
      capillary fed the B. burgdorferi B31 clonal isolate 5A3. Ticks thus infected were
      either left to rest for 4 weeks (Group I) or fed to repletion on a mouse (Group
      II). The contents of each tick from both groups were cultured and 10 B.
      burgdorferi clones from the spirochetal isolate of each tick were obtained. The
      vlsE cassettes from several of these clones were amplified by PCR and sequenced.
      Regardless of whether the isolate was derived from Group I or Group II ticks, no
      changes were observed in the vlsE sequence. In contrast, vlsE cassettes amplified
      from B. burgdorferi clones derived from a mouse that was infected with B31-5A3
      capillary-fed nymphs showed considerable recombination. It follows that vlsE
      recombination does not occur in the tick vector.

PMID- 11598085
TI  - Potential role for a carbohydrate moiety in anti-Candida activity of human oral
      epithelial cells.
AB  - Candida albicans is both a commensal and a pathogen at the oral mucosa. Although
      an intricate network of host defense mechanisms are expected for protection
      against oropharyngeal candidiasis, anti-Candida host defense mechanisms at the
      oral mucosa are poorly understood. Our laboratory recently showed that primary
      epithelial cells from human oral mucosa, as well as an oral epithelial cell line,
      inhibit the growth of blastoconidia and/or hyphal phases of several Candida
      species in vitro with a requirement for cell contact and with no demonstrable
      role for soluble factors. In the present study, we show that oral epithelial cell
      mediated anti-Candida activity is resistant to gamma-irradiation and is not
      mediated by phagocytosis, nitric oxide, hydrogen peroxide, and superoxide
      oxidative inhibitory pathways or by nonoxidative components such as soluble
      defensin and calprotectin peptides. In contrast, epithelial cell-mediated anti
      Candida activity was sensitive to heat, paraformaldehyde fixation, and
      detergents, but these treatments were accompanied by a significant loss in
      epithelial cell viability. Treatments that removed existing membrane protein or
      lipid moieties in the presence or absence of protein synthesis inhibitors had no
      effect on epithelial cell inhibitory activity. In contrast, the epithelial cell
      mediated anti-Candida activity was abrogated after treatment of the epithelial
      cells with periodic acid, suggesting a role for carbohydrates. Adherence of C.
      albicans to oral epithelial cells was unaffected, indicating that the
      carbohydrate moiety is exclusively associated with the growth inhibition
      activity. Subsequent studies that evaluated specific membrane carbohydrate
      moieties, however, showed no role for sulfated polysaccharides, sialic acid
      residues, or glucose- and mannose-containing carbohydrates. These results suggest
      that oral epithelial cell-mediated anti-Candida activity occurs exclusively with
      viable epithelial cells through contact with C. albicans by an as-yet-undefined
      carbohydrate moiety.

PMID- 11598086
TI  - Relative importance of NF-kappaB p50 in mycobacterial infection.
AB  - To understand the role of NF-kappaB in the development of murine tuberculosis in
      vivo, NF-kappaB p50 knockout mice were infected with Mycobacterium tuberculosis
      by placing them in the exposure chamber of an airborne-infection apparatus. These
      mice developed multifocal necrotic pulmonary lesions or lobar pneumonia. Compared
      with the levels in wild-type mice, pulmonary inducible nitric oxide synthase,
      interleukin-2 (IL-2), gamma interferon, and tumor necrosis factor alpha mRNA
      levels were significantly low but expression of IL-10 and transforming growth
      factor beta mRNAs were within the normal ranges. The pulmonary IL-6 mRNA
      expression level was higher. Therefore, NF-kappaB and its interaction with host
      cells play an important role in the pathogenesis of tuberculosis.

PMID- 11598087
TI  - Three-dimensional tissue assemblies: novel models for the study of Salmonella
      enterica serovar Typhimurium pathogenesis.
AB  - The lack of readily available experimental systems has limited knowledge
      pertaining to the development of Salmonella-induced gastroenteritis and diarrheal
      disease in humans. We used a novel low-shear stress cell culture system developed
      at the National Aeronautics and Space Administration in conjunction with
      cultivation of three-dimensional (3-D) aggregates of human intestinal tissue to
      study the infectivity of Salmonella enterica serovar Typhimurium for human
      intestinal epithelium. Immunohistochemical characterization and microscopic
      analysis of 3-D aggregates of the human intestinal epithelial cell line Int-407
      revealed that the 3-D cells more accurately modeled human in vivo differentiated
      tissues than did conventional monolayer cultures of the same cells. Results from
      infectivity studies showed that Salmonella established infection of the 3-D cells
      in a much different manner than that observed for monolayers. Following the same
      time course of infection with Salmonella, 3-D Int-407 cells displayed minimal
      loss of structural integrity compared to that of Int-407 monolayers. Furthermore,
      Salmonella exhibited significantly lower abilities to adhere to, invade, and
      induce apoptosis of 3-D Int-407 cells than it did for infected Int-407
      monolayers. Analysis of cytokine expression profiles of 3-D Int-407 cells and
      monolayers following infection with Salmonella revealed significant differences
      in expression of interleukin 1alpha (IL-1alpha), IL-1beta, IL-6, IL-1Ra, and
      tumor necrosis factor alpha mRNAs between the two cultures. In addition,
      uninfected 3-D Int-407 cells constitutively expressed higher levels of
      transforming growth factor beta1 mRNA and prostaglandin E2 than did uninfected
      Int-407 monolayers. By more accurately modeling many aspects of human in vivo
      tissues, the 3-D intestinal cell model generated in this study offers a novel
      approach for studying microbial infectivity from the perspective of the host
      pathogen interaction.

PMID- 11598089
TI  - Activity and cross-reactivity of antibodies induced in mice by immunization with
      a group B meningococcal conjugate.
AB  - The capsular polysaccharide of group B Neisseria meningitidis is composed of a
      linear homopolymer of alpha(2-8) N-acetyl neuraminic acid or polysialic acid
      (PSA) that is also carried by isoforms of the mammalian neural cell adhesion
      molecule (NCAM), which is especially expressed on brain cells during development.
      Here we analyzed the ability of antibodies induced by the candidate vaccine N
      propionyl polysaccharide tetanus toxoid conjugate to recognize PSA-NCAM. We
      hyperimmunized mice to produce a pool of antisera and a series of immunoglobulin
      G monoclonal antibodies and evaluated their self-reactivity profile by using a
      battery of tests (immunoprecipitation, immunoblotting, and immunofluorescence
      detection on live cells and human tissue sections) chosen for their sensitivity
      and specificity to detect PSA-NCAM in various environments. We also searched for
      the effects of the vaccine-induced antibodies in two functional assays involving
      cell lysis or cell migration. Although they were highly bactericidal, all the
      antibodies tested showed very low or no recognition of PSA-NCAM, in contrast to
      PSA-specific monoclonal antibodies used as controls. Different patterns of cross
      reactions were revealed by the tests used, likely due to affinity and specificity
      differences among the populations of induced antibodies. Furthermore, neither
      cell lysis nor perturbation of migration was observed in the presence of the
      tested antibodies. Importantly, we showed that whereas enzymatic removal of PSA
      groups from the surfaces of live cells perturbed their migration, blocking them
      with PSA-specific antibodies was not functionally detrimental. Taken together,
      our data indicated that this candidate vaccine induced antibodies that could not
      demonstrate an immunopathologic effect.

PMID- 11598088
TI  - Characterization of antiapoptotic activities of Chlamydia pneumoniae in human
      cells.
AB  - Chlamydia pneumoniae is an obligate intracellular bacterium which frequently
      causes airway infection in humans and has been implicated in atherosclerosis.
      Here we show that infection with C. pneumoniae protects HeLa human epithelioid
      cells against apoptosis induced by external stimuli. In infected HeLa cells,
      apoptosis induced by staurosporine and CD95-death-receptor signaling was strongly
      reduced. Upon treatment with staurosporine, generation of effector caspase
      activity, processing of caspase-3 and caspase-9 and cytochrome c redistribution
      were all profoundly inhibited in cells infected with C. pneumoniae. Bacterial
      protein synthesis during early infection was required for this inhibition.
      Furthermore, cytochrome c-induced processing and activation of caspases were
      inhibited in cytosolic extracts from infected cells, suggesting that a C.
      pneumoniae-dependent antiapoptotic factor was generated in the cytosol upon
      infection. Infection with C. pneumoniae failed to induce significant NF-kappaB
      activation in HeLa cells, indicating that no NF-kappaB-dependent cellular factors
      were involved in the protection against apoptosis. These results show that C.
      pneumoniae is capable of interfering with the host cell's apoptotic apparatus at
      probably at least two steps in signal transduction and might explain the
      propensity of these bacteria to cause chronic infections in humans.

PMID- 11598090
TI  - Identification of genes induced in vivo during Klebsiella pneumoniae CG43
      infection.
AB  - A novel in vivo expression technology (IVET) was performed to identify Klebsiella
      pneumoniae CG43 genes that are specifically expressed during infection of BALB/c
      mice. The IVET employed a UDP glucose pyrophosphorylase (galU)-deficient mutant
      of K. pneumoniae which is incapable of utilizing galactose and synthesizing
      capsular polysaccharide, as demonstrated by its low virulence to BALB/c mice and
      a white nonmucoid colony morphology on MacConkey-galactose agar. By using a
      functional galU gene as the reporter, an IVE promoter could render the galU
      mutant virulent while maintaining the white nonmucoid colony phenotype. A total
      of 20 distinct sequences were obtained through the in vivo selection. Five of
      them have been identified previously as virulence-associated genes in other
      pathogens, while another five with characterized functions are involved in
      regulation and transportation of nutrient uptake, biosynthesis of isoprenoids,
      and protein folding. No known functions have been attributed to the other 10
      sequences. We have also demonstrated that 2 of the 20 IVE genes turn on under
      iron deprivation, whereas the expression of another five genes was found to be
      activated in the presence of paraquat, a superoxide generator.

PMID- 11598091
TI  - Assessment of internalization and viability of Porphyromonas gingivalis in KB
      epithelial cells by confocal microscopy.
AB  - Porphyromonas gingivalis (P. gingivalis) is considered to be one of the main
      periodontal pathogens. The goal of this work was to confirm the ability of P.
      gingivalis to invade host cells. We detected P. gingivalis inside KB cells by
      confocal microscopy and analyzed the various aspects of the adherence and
      internalization process. Lysates of P. gingivalis-infected KB cells were also
      examined using anaerobic growth techniques. The results showed the viability and
      ability to replicate, inside the host cells, of the internalized pathogen. The
      production of vesicles was also tracked for the first time. Confocal microscopy
      revealed P. gingivalis in a perinuclear position.

PMID- 11598092
TI  - Inhibition of attaching and effacing lesion formation following enteropathogenic
      Escherichia coli and Shiga toxin-producing E. coli infection.
AB  - Enteropathogenic Escherichia coli (EPEC) and Shiga toxin-producing E. coli (STEC)
      induce cytoskeletal changes in infected epithelial cells. To further characterize
      host cytosolic responses to infection, a series of specific cell-signaling
      inhibitors were employed. Initial bacterial adhesion to HEp-2 epithelial cells
      was not reduced, whereas alpha-actinin accumulation in infected cells was blocked
      by a phosphoinositide-specific phospholipase C inhibitor (ET-18-OCH3),
      phosphoinositide 3-kinase inhibitors (wortmannin and LY294002), and a 5
      lipoxygenase inhibitor, nordihydroguaretic acid. A cyclooxygenase-2 inhibitor (NS
      398), however, did not block alpha-actinin reorganization in response to EPEC and
      STEC infections. Understanding signal transduction responses to enteric pathogens
      could provide the basis for the development of novel therapeutic strategies.

PMID- 11598093
TI  - Histopathological studies on virulence of dipeptidyl aminopeptidase IV (DPPIV) of
      Porphyromonas gingivalis in a mouse abscess model: use of a DPPIV-deficient
      mutant.
AB  - To elucidate the role of dipeptidyl aminopeptidase IV (DPPIV) in the virulence of
      Porphyromonas gingivalis, mice were infected with either a wild-type strain or a
      DPPIV-deficient mutant using an abscess model. Histopathological analysis of the
      resulting lesions indicated that DPPIV participates in virulence through the
      destruction of connective tissue and the less effective mobilization of
      inflammatory cells.

PMID- 11598094
TI  - Resistance of T-cell receptor delta-chain-deficient mice to experimental Candida
      albicans vaginitis.
AB  - Conditions consistent with tolerance or immunoregulation have been observed in
      experimental Candida albicans vaginal infections. The present study investigated
      the role of gamma/delta T cells in experimental vaginal candidiasis. Results
      showed that T-cell receptor delta-chain-knockout mice had significantly less
      vaginal fungal burden when compared to wild-type mice, suggesting an
      immunoregulatory role for gamma/delta T cells in Candida vaginitis.

PMID- 11598095
TI  - High-level expression of NRAMP1 in peripheral blood cells and tuberculous
      granulomas from Mycobacterium bovis-infected bovines.
AB  - By Western blotting, we demonstrate high-level expression of NRAMP1 proteins in
      peripheral blood cells and granulomas of Mycobacterium bovis-infected bovines.
      Immunohistochemistry of granulomatous lesions showed heavily labeled epithelioid
      macrophages and Langhans cells. These data suggest that M. bovis infection
      enhances NRAMP1 expression and that active tuberculosis can occur despite this
      response.

PMID- 11598096
TI  - Comparative analysis of lipopolysaccharide-induced tumor necrosis factor alpha
      activity in serum and lethality in mice and rabbits pretreated with the
      staphylococcal superantigen toxic shock syndrome toxin 1.
AB  - Host susceptibility to lipopolysaccharide (LPS) is correlated with the levels of
      circulating tumor necrosis factor alpha (TNF-alpha) that develop in response to
      circulating LPS. Mice are resistant, relative to rabbits, to the lethal effects
      of LPS. This study indicates that mice and rabbits are equally sensitive to the
      lethal effects of circulating TNF-alpha but that mice are more resistant than
      rabbits to the induction of circulating TNF-alpha by LPS.

PMID- 11598097
TI  - A 4.1-kilodalton polypeptide in the cultural supernatant of Mycoplasma fermentans
      is one of the substances responsible for induction of interleukin-6 production by
      human gingival fibroblasts.
AB  - The cultural supernatant of Mycoplasma fermentans induced interleukin-6
      production by human gingival fibroblasts. The active entities were divided into
      hydrophilic and hydrophobic substances. In this study, we purified a 4.1
      kilodalton polypeptide from the hydrophilic substances. It reacted with
      polyclonal antibodies to M. fermentans and activated human macrophages.

PMID- 11598098
TI  - Urethral cytokine and immune responses in Chlamydia trachomatis-infected males.
AB  - Penile urethral swabs collected from PCR-confirmed Chlamydia trachomatis
      infected, C. trachomatis-uninfected, and non-C. trachomatis-infected,
      nongonococcal urethritis-infected males were analyzed for cytokine, total
      immunoglobulin (Ig), and specific antibody levels by enzyme-linked immunosorbent
      assay. Differential cellular components of the swab transport medium were also
      enumerated for the same groups. Although low, the levels of C. trachomatis
      specific IgA and IgG antibodies and interleukin 8 cytokine were significantly
      higher in C. trachomatis-infected individuals. There were no significant
      differences in the levels of seven additional cytokines evaluated.

PMID- 11598099
TI  - Mycobacterium ulcerans cytotoxicity in an adipose cell model.
AB  - An adipose cell (SW872) model was developed to observe cellular necrosis and
      apoptosis upon Mycobacterium ulcerans infection and treatment with mycobacterial
      exudate. Apoptosis was likely due to secreted proteins, while necrosis was likely
      due to mycolactone. Our data suggest that additional factors in M. ulcerans may
      be involved in Buruli ulcer pathogenesis.

PMID- 11598100
TI  - Effect of SpeB and EndoS from Streptococcus pyogenes on human immunoglobulins.
AB  - Streptococcus pyogenes secretes a specific immunoglobulin G (IgG)-protease, SpeB,
      as well as the IgG glycan-hydrolyzing enzyme EndoS. Here we show that SpeB also
      degrades IgA, IgM, IgD, and IgE. We also show that EndoS only hydrolyzes the
      glycan moiety on native but not denatured IgG. Thus, SpeB has a broad
      immunoglobulin-degrading activity, while EndoS is highly specific for IgG.

PMID- 11598101
TI  - Identity of activation molecule 3 on superantigen-stimulated bovine cells is
      CD26.
AB  - Most CD8(+) T cells in cultures of bovine mononuclear cells stimulated with
      staphylococcal enterotoxin C1 develop an unusual phenotype characterized by
      expression of activation molecule 3 (ACT3). This superantigen-dependent phenotype
      may be relevant to immunopathogenesis mediated by certain microbial toxins. The
      size and N-terminal sequence of immunoprecipitated ACT3 indicate that ACT3 is the
      bovine orthologue of CD26.

PMID- 11598102
TI  - Naturally occurring Clostridium perfringens nontoxic alpha-toxin variant as a
      potential vaccine candidate against alpha-toxin-associated diseases.
AB  - Clostridium perfringens mutant strain 121A/91 shows neither enzymatic
      (phospholipase C) nor hemolytic activity. Nevertheless, the cpa gene and the
      corresponding alpha-toxin variant are detectable. Vaccination with this
      genetically constructed alpha-toxin variant, rAT121/91, induces antibodies
      capable of significantly reducing activities induced by wild-type toxin. Thus,
      rAT121/91 could be a useful vaccine candidate.

PMID- 11598103
TI  - Activation of Arp2/3 complex by Wiskott-Aldrich Syndrome protein is linked to
      enhanced binding of ATP to Arp2.
AB  - In response to signaling, the Arp2/3 complex (actin-related proteins 2 and 3
      complex) is activated by binding the C-terminal (WA) domain of proteins of the
      Wiskott-Aldrich Syndrome family to promote the formation of a branched actin
      filament array, responsible for cell protrusion. The Arp2/3 complex exists in
      different structural/functional states: the inactive Arp2/3, the activated
      WA.Arp2/3 complex, the ternary G-actin.WA.Arp2/3 complex, which branches the
      filaments. This work addresses the role of ATP binding in Arp2/3 function. Using
      photo-cross-linking, hydrodynamic, and fluorescence techniques, we show that in
      the inactive Arp2/3 complex only one rapidly exchangeable ATP is tightly bound to
      Arp3 with an affinity of 10(8) m(-1). Upon activation of the Arp2/3 complex by
      WA, ATP binds to Arp2 with high affinity (10(7) m(-1)), implying that a large
      structural change of Arp2 is linked to Arp2/3 activation. ATP is rapidly
      exchangeable on Arp2 and Arp3 in WA.Arp2/3 and G-actin.WA.Arp2/3 complexes. ATP
      is not hydrolyzed in inactive Arp2/3, in WA.Arp2/3, nor in G-actin.WA.Arp2/3.
      Arp2 has a greater specificity than Arp3 for ATP versus ATP analogs. Using
      functional assays of actin polymerization in branched filaments, we show that
      binding of ATP to Arp2 is required for filament branching.

PMID- 11598105
TI  - Enantiospecificity of cholesterol function in vivo.
AB  - The importance of the absolute configuration of cholesterol for its function in
      vivo is unknown. To directly test this question in vivo, we synthesized the
      enantiomer of cholesterol (ent-cholesterol) and tested its ability to substitute
      for natural cholesterol (nat-cholesterol) in the growth, viability, and behavior
      of Caenorhabditis elegans, a cholesterol auxotroph. First-generation animals
      grown on ent-cholesterol were viable with only mild behavioral defects. However,
      ent-cholesterol produced 100% lethality/arrest of their second generation
      progeny. Isotopically labeled ent-cholesterol incorporated into animals,
      indicating that its lethality was not secondary to cholesterol starvation. When
      mixed with nat-cholesterol, ent-cholesterol was not inert; rather, it antagonized
      the activity of nat-cholesterol. These results demonstrate for the first time
      that the absolute configuration of cholesterol, not just its physical properties,
      is essential for its functions in vivo.

PMID- 11598106
TI  - Reversible inhibition of calcineurin by the polyphenolic aldehyde gossypol.
AB  - The reversible inhibition of calcineurin (CaN), which is the only
      Ca(2+)/calmodulin-dependent protein Ser/Thr phosphatase, is thought to be a key
      functional event for most cyclosporin A (CsA)- and tacrolimus (FK506)-mediated
      biological effects. In addition to CaN inhibition, however, CsA and FK506 have
      multiple biochemical effects because of their action in a gain-of-function model
      that requires prior binding to immunophilic proteins. We screened a small
      molecule library for direct inhibitors of CaN using CaN-mediated
      dephosphorylation of (33)P-labeled 19-residue phosphopeptide substrate (RII
      phosphopeptide) as an assay and found the polyphenolic aldehyde gossypol to be a
      novel CaN inhibitor. Unlike CsA and FK506, gossypol does not require a matchmaker
      protein for reversible CaN inhibition with an IC(50) value of 15 microm.
      Gossypolone, a gossypol analog, showed improved inhibition of both RII
      phosphopeptide and p-nitrophenyl phosphate dephosphorylation with an IC(50) of 9
      and 6 microm, respectively. In contrast, apogossypol hexaacetate was inactive.
      Gossypol acts noncompetitively, interfering with the binding site for the
      cyclophilin 18.CsA complex in CaN. In contrast to CsA and FK506, gossypol does
      not inactivate the peptidyl-prolyl-cis/trans-isomerase activity of immunophilins.
      Similar to CsA and FK506, T cell receptor signaling induced by phorbol 12
      myristate 13-acetate/ionomycin is inhibited by gossypol in a dose-dependent
      manner, demonstrated by the inhibition of nuclear factor of activated T cell
      (NFAT) c1 translocation from the cytosol into the nucleus and suppression of NFAT
      luciferase reporter gene activity.

PMID- 11598104
TI  - 5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12
      myotubes in response to 5-aminoimidazole-4-carboxamide riboside.
AB  - Exercise is known to increase insulin sensitivity and is an effective form of
      treatment for the hyperglycemia observed in type 2 diabetes. Activation of 5'-AMP
      activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide riboside
      (AICAR), exercise, or electrically stimulated contraction leads to increased
      glucose transport in skeletal muscle. Here we report the first evidence of a
      direct interaction between AMPK and the most upstream component of the insulin
      signaling cascade, insulin receptor substrate-1 (IRS-1). We find that AMPK
      rapidly phosphorylates IRS-1 on Ser-789 in cell-free assays as well as in mouse
      C2C12 myotubes incubated with AICAR. In the C2C12 myotubes activation of AMPK by
      AICAR matched the phosphorylation of IRS-1 on Ser-789. This phosphorylation
      correlates with a 65% increase in insulin-stimulated IRS-1-associated
      phosphatidylinositol 3-kinase activity in C2C12 myotubes preincubated with AICAR.
      The binding of phosphatidylinositol 3-kinase to IRS-1 was not affected by AICAR.
      These results demonstrate the existence of an interaction between AMPK and early
      insulin signaling that could be of importance to our understanding of the
      potentiating effects of exercise on insulin signaling.

PMID- 11598107
TI  - Crustacean immunity. Antifungal peptides are generated from the C terminus of
      shrimp hemocyanin in response to microbial challenge.
AB  - We report here the isolation from plasma of two penaeid shrimp species of novel
      peptides/polypeptides with exclusive antifungal activities. A set of three
      molecules was purified with molecular masses at 2.7 kDa (Penaeus vannamei), 7.9
      kDa, and 8.3 kDa (Penaeus stylirostris). Primary structure determination was
      performed by a combination of Edman degradation and mass spectrometry. The
      peptides display 95-100% sequence identity with a C-terminal sequence of
      hemocyanin, indicating that they are cleaved fragments of the shrimp respiratory
      protein. Specific immunodetection of the hemocyanin-derived (poly)peptides
      revealed that experimental microbial infections increase their relative
      concentration in plasma as compared with nonstimulated animals. Thus, the
      production of antifungal (poly)peptides by limited proteolysis of hemocyanin
      could be relevant to a shrimp immune reaction that would confer a new function to
      the multifunctional respiratory pigment of crustaceans.

PMID- 11598108
TI  - Mapping of epitopes in discoidin domain receptor 1 critical for collagen binding.
AB  - The binding and activation of the discoidin domain receptor 1 by collagen has led
      to the conclusion that proteins from the extracellular matrix can directly induce
      receptor tyrosine kinase-mediated signaling cascades. A region in the
      extracellular domain of DDR1 homologous to the Dictyostelium discoideum protein
      discoidin-I is also present in the secreted human protein RS1. Mutations in RS1
      cause retinoschisis, a genetic disorder characterized by ablation of the retina.
      By introducing point mutations into the discoidin domain of DDR1 at positions
      homologous to the retinoschisis mutations, ligand binding epitopes in the
      discoidin domain of DDR1 were mapped. Surprisingly, some residues only affected
      receptor phosphorylation, whereas others influenced both collagen-binding and
      receptor activation. Furthermore, two truncated DDR1 variants, lacking either the
      discoidin domain or the stalk region between the discoidin and transmembrane
      domain, were generated. We showed that (i) the discoidin domain was necessary and
      sufficient for collagen binding, (ii) only the region between discoidin and
      transmembrane domain was glycosylated, and (iii) the entire extracellular domain
      was essential for transmembrane signaling. Using these results, we were able to
      predict key sites in the collagen-binding epitope of DDR1 and to suggest a
      potential mechanism of signaling.

PMID- 11598109
TI  - Transforming growth factor-beta inhibition of insulin-like growth factor-binding
      protein-5 synthesis in skeletal muscle cells involves a c-Jun N-terminal kinase
      dependent pathway.
AB  - Transforming growth factor-beta (TGF-beta) and insulin-like growth factors (IGFs)
      play critical roles in the control of myogenesis. Insulin-like growth factor
      binding protein-5 (IGFBP-5), by regulating the bioavailability of IGFs, is
      involved in controlling IGF-dependent differentiation. We investigated the
      effects of TGF-beta on the IGFBP-5 production induced by IGFs in mouse myoblasts.
      TGF-beta leads to a decrease in IGFBP-5 synthesis at both transcript and protein
      levels, and blocked muscle differentiation. The Smad proteins and the c-Jun N
      terminal kinase (JNK) have been shown to be involved in TGF-beta signaling
      pathways. We provide evidence that the JNK pathway, rather than Smad proteins, is
      involved in the response of muscle cells to TGF-beta. This factor failed to
      stimulate the GAL4-Smad 2/3 transcriptional activities of the constructs used to
      transfect myoblasts. Moreover, stable expression of the antagonistic Smad7 did
      not abolish the inhibitory effect of TGF-beta on IGFBP-5 production whereas
      expression of a dominant-negative version of MKK4, an upstream activator of JNK,
      did. We also showed, using a specific inhibitor, that the p38 mitogen-activated
      protein kinase (p38 MAPK) was not involved in the inhibition of IGFBP-5
      production. Thus, TGF-beta-mediated IGFBP-5 inhibition is independent of Smads
      and requires activation of the JNK signaling pathway.

PMID- 11598111
TI  - MDR1 P-glycoprotein reduces influx of substrates without affecting membrane
      potential.
AB  - MDR1 (multidrug resistance) P-glycoprotein (Pgp; ABCB1) decreases intracellular
      concentrations of structurally diverse drugs. Although Pgp is generally thought
      to be an efflux transporter, the mechanism of action remains elusive. To
      determine whether Pgp confers drug resistance through changes in transmembrane
      potential (E(m)) or ion conductance, we studied electrical currents and drug
      transport in Pgp-negative MCF-7 cells and MCF-7/MDR1 stable transfectants that
      were established and maintained without chemotherapeutic drugs. Although E(m) and
      total membrane conductance did not differ between MCF-7 and MCF-7/MDR1 cells, Pgp
      reduced unidirectional influx and steady-state cellular content of Tc-Sestamibi,
      a substrate for MDR1 Pgp, without affecting unidirectional efflux of substrate
      from cells. Depolarization of membrane potentials with various concentrations of
      extracellular K(+) in the presence of valinomycin did not inhibit the ability of
      Pgp to reduce intracellular concentration of Tc-Sestamibi, strongly suggesting
      that the drug transport activity of MDR1 Pgp is independent of changes in E(m) or
      total ion conductance. Tetraphenyl borate, a lipophilic anion, enhanced
      unidirectional influx of Tc-Sestamibi to a greater extent in MCF-7/MDR1 cells
      than in control cells, suggesting that Pgp may, directly or indirectly, increase
      the positive dipole potential within the plasma membrane bilayer. Overall, these
      data demonstrate that changes in E(m) or macroscopic conductance are not coupled
      with function of Pgp in multidrug resistance. The dominant effect of MDR1 Pgp in
      this system is reduction of drug influx, possibly through an increase in
      intramembranous dipole potential.

PMID- 11598110
TI  - Hydrogen peroxide generated during cellular insulin stimulation is integral to
      activation of the distal insulin signaling cascade in 3T3-L1 adipocytes.
AB  - In a variety of cell types, insulin stimulation elicits the rapid production of
      H(2)O(2), which causes the oxidative inhibition of protein-tyrosine phosphatases
      and enhances the tyrosine phosphorylation of proteins in the early insulin action
      cascade (Mahadev, K., Zilbering, A., Zhu, L., and Goldstein, B. J. (2001) J.
      Biol. Chem. 276, 21938-21942). In the present work, we explored the potential
      role of insulin-induced H(2)O(2) generation on downstream insulin signaling using
      diphenyleneiodonium (DPI), an inhibitor of cellular NADPH oxidase that blocks
      insulin-stimulated cellular H(2)O(2) production. DPI completely inhibited the
      activation of phosphatidylinositol (PI) 3'-kinase activity by insulin and reduced
      the insulin-induced activation of the serine kinase Akt by up to 49%; these
      activities were restored when H(2)O(2) was added back to cells that had been
      pretreated with DPI. Interestingly, the H(2)O(2)-induced activation of Akt was
      entirely mediated by upstream stimulation of PI 3'-kinase activity, since
      treatment of 3T3-L1 adipocytes with the PI 3'-kinase inhibitors wortmannin or
      LY294002 completely blocked the subsequent activation of Akt by exogenous
      H(2)O(2). Preventing oxidant generation with DPI also blocked insulin-stimulated
      glucose uptake and GLUT4 translocation to the plasma membrane, providing further
      evidence for an oxidant signal in the regulation of the distal insulin-signaling
      cascade. Finally, in contrast to the cellular mechanism of H(2)O(2) generation by
      other growth factors, such as platelet-derived growth factor, we also found that
      insulin-stimulated cellular production of H(2)O(2) may occur through a unique
      pathway, independent of cellular PI 3'-kinase activity. Overall, these data
      provide insight into the physiological role of insulin-dependent H(2)O(2)
      generation, which is not only involved in the regulation of tyrosine
      phosphorylation events in the early insulin signaling cascade but also has
      important effects on the regulation of downstream insulin signaling, involving
      the activation of PI 3'-kinase, Akt, and ultimately cellular glucose transport in
      response to insulin.

PMID- 11598112
TI  - Trypanosoma cruzi prolyl oligopeptidase Tc80 is involved in nonphagocytic
      mammalian cell invasion by trypomastigotes.
AB  - Trypanosoma cruzi is an intracellular protozoan parasite able to invade a wide
      variety of mammalian cells. To have access to the target organs/cells, the
      parasite must cross the basal laminae and the extracellular matrix (ECM). We
      previously characterized an 80-kDa proteinase (Tc80) secreted by the infective
      trypomastigotes that hydrolyzes native collagens and might be involved in
      infection by degrading ECM components. Here, we present evidence indicating a
      role for Tc80 in the invasion of nonphagocytic cells. Tc80 was classified as a
      member of the prolyl oligopeptidase (POP) family of serine proteases and was also
      found to hydrolyze fibronectin. Selective inhibitors for POP Tc80 were
      synthesized that blocked parasite entry into cells. Blockage occurred when
      trypomastigotes were preincubated with irreversible inhibitors but not after host
      cell preincubation, and the blockage correlated with inhibition of POP Tc80
      activity in treated parasites. These data and the enzyme location inside a
      vesicular compartment close to the flagellar pocket, a specialized domain in
      endocytosis/exocytosis, strongly suggest a role for POP Tc80 in the maturation of
      parasite protein(s) and/or, after secretion, in a local action on parasite or
      host cell/ECM components required for invasion.

PMID- 11598113
TI  - The conserved sites for the FK506-binding proteins in ryanodine receptors and
      inositol 1,4,5-trisphosphate receptors are structurally and functionally
      different.
AB  - We compared the interaction of the FK506-binding protein (FKBP) with the type 3
      ryanodine receptor (RyR3) and with the type 1 and type 3 inositol 1,4,5
      trisphosphate receptor (IP(3)R1 and IP(3)R3), using a quantitative GST-FKBP12 and
      GST-FKBP12.6 affinity assay. We first characterized and mapped the interaction of
      the FKBPs with the RyR3. GST-FKBP12 as well as GST-FKBP12.6 were able to bind
      approximately 30% of the solubilized RyR3. The interaction was completely
      abolished by FK506, strengthened by the addition of Mg(2+), and weakened in the
      absence of Ca(2+) but was not affected by the addition of cyclic ADP-ribose. By
      using proteolytic mapping and site-directed mutagenesis, we pinpointed Val(2322),
      located in the central modulatory domain of the RyR3, as a critical residue for
      the interaction of RyR3 with FKBPs. Substitution of Val(2322) for leucine (as in
      IP(3)R1) or isoleucine (as in RyR2) decreased the binding efficiency and shifted
      the selectivity to FKBP12.6; substitution of Val(2322) for aspartate completely
      abolished the FKBP interaction. Importantly, the occurrence of the valylprolyl
      residue as alpha-helix breaker was an important determinant of FKBP binding. This
      secondary structure is conserved among the different RyR isoforms but not in the
      IP(3)R isoforms. A chimeric RyR3/IP(3)R1, containing the core of the FKBP12
      binding site of IP(3)R1 in the RyR3 context, retained this secondary structure
      and was able to interact with FKBPs. In contrast, IP(3)Rs did not interact with
      the FKBP isoforms. This indicates that the primary sequence in combination with
      the local structural environment plays an important role in targeting the FKBPs
      to the intracellular Ca(2+)-release channels. Structural differences in the FKBP
      binding site of RyRs and IP(3)Rs may contribute to the occurrence of a stable
      interaction between RyR isoforms and FKBPs and to the absence of such interaction
      with IP(3)Rs.

PMID- 11598114
TI  - Significance of local electrostatic interactions in staphylococcal nuclease
      studied by site-directed mutagenesis.
AB  - In this paper, we show that amino acids Glu(73) and Asp(77) of staphylococcal
      nuclease cooperate unequally with Glu(75) to stabilize its structure located
      between the C-terminal helix and beta-barrel of the protein. Amino acid
      substitutions E73G and D77G cause losses of the catalytic efficiency of 24 and
      16% and cause thermal stability losses of 22 and 26%, respectively, in comparison
      with the wild type (WT) protein. However, these changes do not significantly
      change global and local secondary structures, based on measurements of
      fluorescence and CD(222 nm). Furthermore, x-ray diffraction analysis of the E75G
      protein shows that the overall structure of mutant and WT proteins is similar.
      However, this mutation does cause a loss of essential hydrogen bonding and charge
      interactions between Glu(75) and Lys(9), Tyr(93), and His(121). In experiments
      using double point mutations, E73G/D77G, E73G/E75G, and E75G/D77G, significant
      changes are seen in all mutants in comparison with WT protein as measured by
      fluorescence and CD spectroscopy. The losses of thermal stability are 47, 59, and
      58%, for E73G/D77G, E73G/E75G, and E75G/D77G, respectively. The triple mutant,
      E73G/E75G/D77G, results in fluorescence intensity and CD(222 nm) close to those
      of the denatured state and in a thermal stability loss of 65% relative to the WT
      protein. Based on these results, we propose a model in which significant
      electrostatic interactions result in the formation of a locally stable structure
      in staphylococcal nuclease.

PMID- 11598115
TI  - The Di-leucine motif of vesicle-associated membrane protein 4 is required for its
      localization and AP-1 binding.
AB  - Heterotetrameric adaptor complexes and SNAREs play key roles in the specificity
      of membrane budding and fusion. Here we test the hypothesis that vesicle budding
      and membrane fusion are coupled by the interaction of these molecules. We
      investigate the role of the di-leucine motif of vesicle-associated membrane
      protein 4 (VAMP4) in adaptor binding and localization of VAMP4. Mutation of the
      di-leucine motif inhibits AP-1 binding in vitro and affects the steady state
      distribution of VAMP4 in vivo.

PMID- 11598116
TI  - Hepatic very low density lipoprotein-ApoB overproduction is associated with
      attenuated hepatic insulin signaling and overexpression of protein-tyrosine
      phosphatase 1B in a fructose-fed hamster model of insulin resistance.
AB  - A fructose-fed hamster model of insulin resistance was previously documented to
      exhibit marked hepatic very low density lipoprotein (VLDL) overproduction. Here,
      we investigated whether VLDL overproduction was associated with down-regulation
      of hepatic insulin signaling and insulin resistance. Hepatocytes isolated from
      fructose-fed hamsters exhibited significantly reduced tyrosine phosphorylation of
      the insulin receptor and insulin receptor substrates 1 and 2.
      Phosphatidylinositol 3-kinase activity as well as insulin-stimulated Akt-Ser473
      and Akt-Thr308 phosphorylation were also significantly reduced with fructose
      feeding. Interestingly, the protein mass and activity of protein-tyrosine
      phosphatase-1B (PTP-1B) were significantly higher in fructose-fed hamster
      hepatocytes. Chronic ex vivo exposure of control hamster hepatocytes to high
      insulin also appeared to attenuate insulin signaling and increase PTP-1B.
      Elevation in PTP-1B coincided with marked suppression of ER-60, a cysteine
      protease postulated to play a role in intracellular apoB degradation, and an
      increase in the synthesis and secretion of apoB. Sodium orthovanadate, a general
      phosphatase inhibitor, partially restored insulin receptor phosphorylation and
      significantly reduced apoB secretion. In summary, we hypothesize that fructose
      feeding induces hepatic insulin resistance at least in part via an increase in
      expression of PTP-1B. Induction of hepatic insulin resistance may then contribute
      to reduced apoB degradation and enhanced VLDL particle assembly and secretion.

PMID- 11598117
TI  - Cysteine 144 in the third transmembrane domain of the creatine transporter is
      located close to a substrate-binding site.
AB  - All creatine transporters contain a cysteine residue (Cys(144)) in the third
      transmembrane domain that is not present in other members of the Na+,Cl(-)
      dependent family of neurotransmitter transporters. Site-directed mutagenesis and
      reaction with methane thiosulfonates were used to investigate the importance of
      Cys(144) for transporter function. Replacement of Cys(144) with Ser did not
      significantly affect the kinetics or activity of the transporter, whereas a C144A
      mutant had a higher K(m) (0.33 compared with 0.18 mm). Substitution of Cys(144)
      with Leu gave a mutant with a 5-fold higher K(m) and a reduced specificity for
      substrate. Low concentrations of 2-aminoethyl methanethiosulfonate (MTSEA)
      resulted in rapid inactivation of the creatine transporter. The C144S mutant was
      resistant to inactivation, indicating that modification of Cys(144) was
      responsible for the loss of transport activity. Creatine and analogues that
      function as substrates of the creatine transporter were able to protect from
      MTSEA inactivation. Na+ and Cl(-) ions were not necessary for MTSEA inactivation,
      but Na+ was found to be important for creatine protection from inactivation. Our
      results indicate that cysteine 144 is close to the binding site or part of a
      permeation channel for creatine.

PMID- 11598118
TI  - Short term effect of aldosterone on Na,K-ATPase cell surface expression in kidney
      collecting duct cells.
AB  - Aldosterone controls extracellular volume and blood pressure by regulating Na+
      reabsorption, in particular by epithelia of the distal nephron. A main regulatory
      site of this transcellular transport is the epithelial sodium channel (ENaC) that
      mediates luminal Na+ influx. The Na,K-ATPase (Na+ pump) that coordinately
      extrudes Na+ across the basolateral membrane is known to be regulated by short
      term aldosterone as well. We now show that in the cortical collecting duct (CCD)
      from adrenalectomized rats, the increase in Na,K-ATPase activity (approximately 3
      fold in 3 h), induced by a single aldosterone injection, can be fully accounted
      by the increase in Na,K-ATPase cell surface expression (+ 497 +/- 35%). The short
      term aldosterone action was further investigated in cultured mouse collecting
      duct principal cells mpkCCD(cl4). Within 2 h, maximal Na,K-ATPase function
      assessed by Na+ pump current (I(p)) measurements and Na,K-ATPase cell surface
      expression were increased by 20-50%. Aldosterone did not modify the Na+
      dependence of the Na+ pumps and induced transcription- and translation-dependent
      actions on pump surface expression and current independently of ENaC-mediated Na+
      influx. In summary, short term aldosterone directly increases the cell surface
      expression of pre-existing Na+ pumps in kidney CCD target cells. Thus,
      aldosterone controls Na+ reabsorption in the short term not only by regulating
      the apical cell surface expression of ENaC (Loffing, J., Zecevic, M., Feraille,
      E., Kaissling, B., Asher, C., Rossier, B. C., Firestone, G. L., Pearce, D., and
      Verrey, F. (2001) Am. J. Physiol. 280, F675-F682) but also by coordinately acting
      on the basolateral cell surface expression of the Na,K-ATPase.

PMID- 11598119
TI  - Two forms of mitochondrial DNA ligase III are produced in Xenopus laevis oocytes.
AB  - Full-length cDNAs for DNA ligase IV and the alpha and beta isoforms of DNA ligase
      III were cloned from Xenopus laevis to permit study of the genes encoding
      mitochondrial DNA ligase. DNA ligase III alpha and III beta share a common NH(2)
      terminus that encodes a mitochondrial localization signal capable of targeting
      green fluorescent protein to mitochondria while the NH(2) terminus of DNA ligase
      IV does not. Reverse transcriptase-polymerase chain reaction analyses with adult
      frog tissues demonstrate that while DNA ligase III alpha and DNA ligase IV are
      ubiquitously expressed, DNA ligase III beta expression is restricted to testis
      and ovary. Mitochondrial lysates from X. laevis oocytes contain both DNA ligase
      III alpha and III beta but no detectable DNA ligase IV. Gel filtration,
      sedimentation, native gel electrophoresis, and in vitro cross-linking experiments
      demonstrate that mtDNA ligase III alpha exists as a high molecular weight
      complex. We discuss the possibility that DNA ligase III alpha exists in
      mitochondria in association with novel mitochondrial protein partners or as a
      homodimer.

PMID- 11598120
TI  - Multiple activation loop conformations and their regulatory properties in the
      insulin receptor's kinase domain.
AB  - Low catalytic efficiency of protein kinases often results from intrasteric
      inhibition caused by the activation loop blocking the active site. In the insulin
      receptor's kinase domain, Asp-1161 and Tyr-1162 in the peptide substrate-like
      sequence of the unphosphorylated activation loop can interact with four invariant
      residues in the active site: Lys-1085, Asp-1132, Arg-1136, and Gln-1208.
      Contributions of these six residues to intrasteric inhibition were tested by
      mutagenesis, and the unphosphorylated kinase domains were characterized. The
      mutations Q1208S, K1085N, and Y1162F each relieved intrasteric inhibition,
      increasing catalytic efficiency but without changing the rate-limiting step of
      the reaction. The mutants R1136Q and D1132N were virtually inactive. Steric
      accessibility of the active site was ranked by relative changes in iodide
      quenching of intrinsic fluorescence, and A-loop conformation was ranked by
      limited tryptic cleavage. Together these ranked the openness of the active site
      cleft as R1136Q approximately D1132N > or = D1161A > Y1162F approximately K1085N
      > Q1208S > or = wild-type. These findings demonstrate the importance of specific
      invariant residues for intrasteric inhibition and show that diverse activation
      loop conformations can produce similar steady-state kinetic properties. This
      suggests a broader range of regulatory properties for the activation loop than
      expected from a simple off-versus-on switch for kinase activation.

PMID- 11598121
TI  - A novel c-Myc-responsive gene, JPO1, participates in neoplastic transformation.
AB  - We have identified a novel c-Myc-responsive gene, named JPO1, by representational
      difference analysis. JPO1 responds to two inducible c-Myc systems and behaves as
      a direct c-Myc target gene. JPO1 mRNA expression is readily detectable in the
      thymus, small intestine, and colon, whereas expression is relatively low in
      spleen, bone marrow, and peripheral leukocytes. We cloned a full-length JPO1 cDNA
      that encodes a 47-kDa nuclear protein. To determine the role of JPO1 in Myc
      mediated cellular phenotypes, stable Rat1a fibroblasts overexpressing JPO1 were
      tested and compared with transformed Rat1a-Myc cells. Although JPO1 has a
      diminished transforming activity as compared with c-Myc, JPO1 complements a
      transformation-defective Myc Box II mutant in the Rat1a transformation assay.
      This complementation provides evidence for a genetic link between c-Myc and JPO1.
      Similar to c-Myc, JPO1 overexpression enhances the clonogenicity of CB33 human
      lymphoblastoid cells in methylcellulose assays. These observations suggest that
      JPO1 participates in c-Myc-mediated transformation, supporting an emerging
      concept that c-Myc target genes constitute nodal points in a network of pathways
      that lead from c-Myc to various Myc-related phenotypes and ultimately to
      tumorigenesis.

PMID- 11598122
TI  - DNA unwinding mechanism for the transcriptional activation of momP1 promoter by
      the transactivator protein C of bacteriophage Mu.
AB  - Transcription factor-induced conformational changes in DNA are one of the
      mechanisms of transcription activation. C protein of bacteriophage Mu appears to
      transactivate the mom gene of the phage by this mode. DNA binding by C to its
      site leads to torsional changes that seem to compensate for a weak momP1 promoter
      having a suboptimal spacing of 19 bp between the poor -35 and -10 elements. The C
      mediated unwinding could realign the promoter elements for RNA polymerase
      recruitment to the reoriented promoter. In this study, the model has been tested
      by mutational analysis of the spacer region of momP1 and by assessing the
      strength of the mutant promoters. The response to C-mediated transactivation was
      dependent on the spacer length of the promoters. Mutants with 17-bp spacing
      between the two promoter elements showed reduced activity in the presence of the
      transactivator as compared with their basal level. A synthetic promoter with near
      consensus promoter elements and optimal 17-bp spacing was also tested to evaluate
      the model. The results imply a role for C-mediated unwinding in mom transcription
      activation.

PMID- 11598123
TI  - Circadian regulation of diverse gene products revealed by mRNA expression
      profiling of synchronized fibroblasts.
AB  - Genes under a 24-h regulation period may represent drug targets relevant to
      diseases involving circadian dysfunctions. As a testing model of the circadian
      clock system, we have used synchronized rat fibroblasts that are known to express
      at least six genes in a circadian fashion. We have determined the expression
      patterns of 9957 transcripts every 4 h over a total period of 76 h using high
      density oligonucleotide microarrays. The spectral analysis of our mRNA profiling
      data indicated that approximately 2% (85 genes) of all expressed genes followed a
      robust circadian pattern. We have confirmed the circadian expression of
      previously known clock or clock-driven genes, and we identified 81 novel
      circadian genes. The majority of the circadian-regulated gene products are known
      and are involved in diverse cellular functions. We have classified these
      circadian genes in seven clusters according to their phase of cycling. Our
      pathway analysis of the mRNA profiling data strongly suggests a direct link
      between circadian rhythm and cell cycle.

PMID- 11598124
TI  - Phe71 is essential for chaperone-like function in alpha A-crystallin.
AB  - Experiments with mini-alphaA-crystallin (KFVIFLDVKHFSPEDLTVK) showed that Phe(71)
      in alphaA-crystallin could be essential for the chaperone-like action of the
      protein (Sharma, K. K., Kumar, R. S., Kumar, G. S., and Quinn, P. T. (2000) J.
      Biol. Chem. 275, 3767-3771). In the present study we replaced Phe(71) in rat
      alphaA-crystallin with Gly by site-directed mutagenesis and then compared the
      structural and functional properties of the mutant protein with the wild-type
      protein. There were no differences in molecular size or intrinsic tryptophan
      fluorescence between the proteins. However, 1,1'-bi(4-anilino)naphthalene-5,5'
      disulfonic acid interaction indicated a higher hydrophobicity for the mutant
      protein. Both wild-type and mutant proteins displayed similar secondary structure
      during far UV CD experiments. Near UV CD signal showed a slight difference in the
      tertiary structure around the 285-295 region for the two proteins. The mutant
      protein was totally inactive in suppressing the aggregation of reduced insulin,
      heat-denatured citrate synthase, and alcohol dehydrogenase. However, a marginal
      suppression of beta(L)-crystallin aggregation was observed when mutant alphaA
      crystallin was included. These results suggest that Phe(71) contributes to the
      chaperone-like action of alphaA-crystallin. Therefore we conclude that the 70-88
      region in alphaA-crystallin, identified by us earlier, is the functional
      chaperone site in alphaA-crystallin.

PMID- 11598126
TI  - Identification and biochemical characterization of Arabidopsis thaliana sulfite
      oxidase. A new player in plant sulfur metabolism.
AB  - In mammals and birds, sulfite oxidase (SO) is a homodimeric molybdenum enzyme
      consisting of an N-terminal heme domain and a C-terminal molybdenum domain (EC ).
      In plants, the existence of SO has not yet been demonstrated, while sulfite
      reductase as part of sulfur assimilation is well characterized. Here we report
      the cloning of a plant sulfite oxidase gene from Arabidopsis thaliana and the
      biochemical characterization of the encoded protein (At-SO). At-SO is a
      molybdenum enzyme with molybdopterin as an organic component of the molybdenum
      cofactor. In contrast to homologous animal enzymes, At-SO lacks the heme domain,
      which is evident both from the amino acid sequence and from its enzymological and
      spectral properties. Thus, among eukaryotes, At-SO is the only molybdenum enzyme
      yet described possessing no redox-active centers other than the molybdenum. UV
      visible and EPR spectra as well as apparent K(m) values are presented and
      compared with the hepatic enzyme. Subcellular analysis of crude cell extracts
      showed that SO was mostly found in the peroxisomal fraction. In molybdenum
      cofactor mutants, the activity of SO was strongly reduced. Using antibodies
      directed against At-SO, we show that a cross-reacting protein of similar size
      occurs in a wide range of plant species, including both herbacious and woody
      plants.

PMID- 11598125
TI  - Cyr61, a member of CCN family, is a tumor suppressor in non-small cell lung
      cancer.
AB  - Cysteine-rich protein 61 (Cyr61) is a member of a family of growth factor
      inducible immediate-early genes. It regulates cell adhesion, migration,
      proliferation, and differentiation and is involved in tumor growth. In our
      experiments, the role of Cyr61 in non-small cell lung cancer (NSCLC) was
      examined. Expression of Cyr61 mRNA was decreased markedly in four of five human
      lung tumor samples compared with their normal matched lung samples. NSCLC cell
      lines NCI-H520 and H460, which have no endogenous Cyr61, formed 60-90% fewer
      colonies after being transfected with a Cyr61 cDNA expression vector than cells
      transfected with the same amount of empty vector. After stable transfection of a
      Cyr61 cDNA expression vector, proliferation of both H520-Cyr61 and H460-Cyr61
      sublines decreased remarkably compared with the cells stably transfected with
      empty vector. The addition of antibody against Cyr61 partially rescued the growth
      suppression of both H520-Cyr61 and H460-Cyr61 cells. Cell cycle analysis revealed
      that both H520-Cyr61 and H460-Cyr61 cells developed G(1) arrest, prominently up
      regulated expression of p53 and p21(WAF1), and had decreased activity of cyclin
      dependent kinase 2. The increase of pocket protein pRB2/p130 was also detected in
      these cells. Notably, both of the Cyr61-stably transfected lung cancer cell lines
      developed smaller tumors than those formed by the wild-type cells in nude mice.
      Taken together, we conclude that Cyr61 may play a role as a tumor suppressor in
      NSCLC.

PMID- 11598127
TI  - Regulation of the anaphase-promoting complex by the dual specificity phosphatase
      human Cdc14a.
AB  - Two forms of the anaphase-promoting complex (APC) mediate the degradation of
      critical cell cycle regulators. APC(Cdc20) promotes sister-chromatid separation
      by ubiquitinating securin, whereas APC(Cdh1) ubiquitinates mitotic cyclins,
      allowing the exit from mitosis. Here we show that phosphorylation of human Cdh1
      (hCdh1) by cyclin B-Cdc2 alters the conformation of hCdh1 and prevents it from
      activating APC. A human homologue of yeast Cdc14, human Cdc14a (hCdc14a),
      dephosphorylates hCdh1 and activates APC(Cdh1). In contrast, hCdc14a does not
      affect the activity of APC(Cdc20). hCdc14a is a major phosphatase for hCdh1 and
      localizes to centrosomes in HeLa cells. Therefore, hCdc14a may promote the
      activation of APC(Cdh1) and exit from mitosis in mammalian cells.

PMID- 11598128
TI  - Folded monomer of HIV-1 protease.
AB  - The mature human immunodeficiency virus type 1 protease rapidly folds into an
      enzymatically active stable dimer, exhibiting an intricate interplay between
      structure formation and dimerization. We now show by NMR and sedimentation
      equilibrium studies that a mutant protease containing the R87K substitution
      (PR(R87K)) within the highly conserved Gly(86)-Arg(87)-Asn(88) sequence forms a
      monomer with a fold similar to a single subunit of the dimer. However, binding of
      the inhibitor DMP323 to PR(R87K) produces a stable dimer complex. Based on the
      crystal structure and our NMR results, we postulate that loss of specific
      interactions involving the side chain of Arg(87) destabilizes PR(R87K) by
      perturbing the inner C-terminal beta-sheet (residues 96-99 from each monomer), a
      region that is sandwiched between the two beta-strands formed by the N-terminal
      residues (residues 1-4) in the mature protease. We systematically examined the
      folding, dimerization, and catalytic activities of mutant proteases comprising
      deletions of either one of the terminal regions (residues 1-4 or 96-99) or both.
      Although both N- and C-terminal beta-strands were found to contribute to dimer
      stability, our results indicate that the inner C-terminal strands are absolutely
      essential for dimer formation. Knowledge of the monomer fold and regions critical
      for dimerization may aid in the rational design of novel inhibitors of the
      protease to overcome the problem of drug resistance.

PMID- 11598129
TI  - Developmental regulation of heat shock protein 83 in Leishmania. 3' processing
      and mRNA stability control transcript abundance, and translation id directed by a
      determinant in the 3'-untranslated region.
AB  - Developmental gene regulation in trypanosomatids proceeds exclusively by post
      transcriptional mechanisms. Stability and abundance of heat shock protein (HSP)70
      and HSP83 transcripts in Leishmania increase at mammalian-like temperatures, and
      their translation is enhanced. Here we report that the 3'-untranslated region
      (UTR) of HSP83 (886 nucleotides) confers the temperature-dependent pattern of
      regulation on a chloramphenicol acetyltransferase (CAT) reporter transcript. We
      also show that the majority of the 3'-UTR sequences are required for increasing
      mRNA stability during heat shock. Processing of the HSP70 and HSP83 primary
      transcripts to poly(A)(+) mRNA was more efficient during heat shock; therefore,
      even when stability at 33 degrees C was reduced by deletions in the 3'-UTR,
      transcripts still accumulated to comparable and even higher levels. Translation
      of heat shock transcripts in Leishmania increases dramatically upon temperature
      elevation. Unlike in other eukaryotes in which the 5'-UTR confers preferential
      translation on heat shock transcripts, we show that translational control of
      HSP83 in Leishmania originates from its 3'-UTR. The 5'-UTR alone cannot induce
      translation during heat shock, but it has a minor contribution when combined with
      the HSP83 3'-UTR. We identified an element located between positions 201 and 472
      of the 3'-UTR which is essential for increasing translation of the CAT-HSP83
      reporter RNA at 33-37 degrees C. This region confers preferential translation
      during heat shock even in transcripts that were less stable. Thus, investigating
      the traditionally conserved heat shock response reveals that Leishmania parasites
      use unique pathways for translational control.

PMID- 11598130
TI  - Characterization of regulatory elements on the promoter region of p16(INK4a) that
      contribute to overexpression of p16 in senescent fibroblasts.
AB  - Cyclin-dependent kinase inhibitor p16(INK4a) is implicated in replicative
      senescence, cell immortalization, and tumor generation. However, the mechanism
      regulating its overexpression in senescent cells is unknown. We used the enhanced
      green fluorescent protein reporter system to scan regulatory elements in the
      upstream region of p16(INK4a). The results of 5'-deletion studies indicated that
      the transcription regulatory elements contributing to overexpression of
      p16(INK4a) in senescent cells were located in the region of the p16(INK4a)
      promoter from -622 to -280 bp. According to the results of in vitro DNase I
      footprinting, EMSA, and Southwestern blotting, we found a novel negative
      regulatory element, the INK4a transcription silence element (ITSE), at -491 to 
      485 bp of the p16(INK4a) promoter. A 24-kDa protein that was highly expressed in
      young cells may inhibit the expression of p16(INK4a) by interacting with the
      ITSE. The activity of the p16(INK4a) promoter increased significantly in young
      cells when the ITSE was deleted. The GC-rich region of the p16(INK4a) promoter
      from -466 to -451 was a positive transcription regulatory element. Deletion of
      this region showed 91.4% loss of p16(INK4a) promoter activity in senescent cells,
      and the promoter activity decreased by 41.2% in young cells comparably.

PMID- 11598132
TI  - Heme deficiency selectively interrupts assembly of mitochondrial complex IV in
      human fibroblasts: revelance to aging.
AB  - Heme deficiency was studied in young and old normal human fibroblasts (IMR90).
      Regardless of age, heme deficiency increased the steady-state level of oxidants
      and lipid peroxidation and sensitized the cells to fluctuations in intracellular
      Ca(2+). Heme deficiency selectively decreased the activity and protein content of
      mitochondrial complex IV (cytochrome c oxidase) by 95%, indicating a decrease in
      successful assembly. Complexes I-III and catalase remained intact under
      conditions of heme deficiency, whereas ferrochelatase was up-regulated. Complex
      IV is the only hemeprotein in the cell that contains heme a, which may account
      for its susceptibility. The rate of removal and assembly of complex IV declines
      with age. These findings are relevant to worldwide iron deficiency in women and
      children and to an age-related decline in complex IV in Alzheimer's disease
      patients.

PMID- 11598131
TI  - WISP-1 binds to decorin and biglycan.
AB  - Wnt-1-induced secreted protein 1 (WISP-1) is a member of the CCN (connective
      tissue growth factor, Cyr61, NOV) family of growth factors. Structural and
      experimental evidence suggests that CCN family member activities are modulated by
      their interaction with sulfated glycoconjugates. To elucidate the mechanism of
      action for WISP-1, we characterized the specificity of its tissue and cellular
      interaction and identified binding factors. WISP-1 binding was restricted to the
      stroma of colon tumors and to cells with a fibroblastic phenotype. By using a
      solid phase assay, we showed that human skin fibroblast conditioned media
      contained WISP-1 binding factors. Competitive inhibition with different
      glycosaminoglycans and treatment with glycosaminoglycan lyases and proteases
      demonstrated that binding to the conditioned media was mediated by dermatan
      sulfate proteoglycans. Mass spectrometric analysis identified the isolated
      binding factors as decorin and biglycan. Decorin and biglycan interacted directly
      with WISP-1 and inhibited its binding to components in the conditioned media.
      Similarly, WISP-1 interaction with human skin fibroblasts was inhibited by
      dermatan sulfate, decorin, and biglycan or by treatment of the cell surface with
      dermatan sulfate-specific lyases. Together these results demonstrate that decorin
      and biglycan are WISP-1 binding factors that can mediate and modulate its
      interaction with the surface of fibroblasts. We propose that this specific
      interaction plays a role in the regulation of WISP-1 function.

PMID- 11598134
TI  - Critical role of cAMP-GEFII--Rim2 complex in incretin-potentiated insulin
      secretion.
AB  - Incretins such as glucagon-like peptide-1 and gastric inhibitory
      polypeptide/glucose-dependent insulinotropic peptide are known to potentiate
      insulin secretion mainly through a cAMP/protein kinase A (PKA) signaling pathway
      in pancreatic beta-cells, but the mechanism is not clear. We recently found that
      the cAMP-binding protein cAMP-GEFII (or Epac 2), interacting with Rim2, a target
      of the small G protein Rab3, mediates cAMP-dependent, PKA-independent exocytosis
      in a reconstituted system. In the present study, we investigated the role of the
      cAMP-GEFII--Rim2 pathway in incretin-potentiated insulin secretion in native
      pancreatic beta-cells. Treatment of pancreatic islets with antisense
      oligodeoxynucleotides (ODNs) against cAMP-GEFII alone or with the PKA inhibitor H
      89 alone inhibited incretin-potentiated insulin secretion approximately 50%,
      while a combination of antisense ODNs and H-89 inhibited the secretion
      approximately 80-90%. The effect of cAMP-GEFII on insulin secretion is mediated
      by Rim2 and depends on intracellular calcium as well as on cAMP. Treatment of the
      islets with antisense ODNs attenuated both the first and second phases of insulin
      secretion potentiated by the cAMP analog 8-bromo-cAMP. These results indicate
      that the PKA-independent mechanism involving the cAMP-GEFII--Rim2 pathway is
      critical in the potentiation of insulin secretion by incretins.

PMID- 11598133
TI  - Nedd4 regulates ubiquitination and stability of the guanine-nucleotide exchange
      factor CNrasGEF.
AB  - Cyclic nucleotide ras GEF (CNrasGEF) is a guanine-nucleotide exchange factor
      previously isolated in a screen for Nedd4-WW domain interacting proteins (Pham,
      N., Cheglakov, I., Koch, C. A., de Hoog, C. L., Moran, M. F., and Rotin, D.
      (2000) Curr. Biol. 10, 555-558). It activates Ras in a cAMP-dependent manner and
      Rap-1 independent of cAMP. Here we show that CNrasGEF is a likely substrate of
      the ubiquitin protein ligase Nedd4. CNrasGEF possesses two PY motifs at its C
      terminus that are responsible for binding to Nedd4 in vitro. Moreover, Nedd4 and
      CNrasGEF co-immunoprecipitate from 293T cells expressing ectopic CNrasGEF and
      endogenous Nedd4, and this co-immunoprecipitation is abrogated in PY motif
      mutated CNrasGEF (CNrasGEFDelta2PY). CNrasGEF is ubiquitinated in cells, and this
      ubiquitination is augmented upon overexpression of wt-Nedd4 but is inhibited in
      cells overexpressing a catalytically inactive Nedd4 (Nedd4(CS)) or in cells
      expressing CNrasGEFDelta2PY, which cannot bind Nedd4. Moreover, pulse-chase
      experiments have demonstrated that the half-life of CNrasGEF is reduced 5-fold
      (from approximately 10 to approximately 2 h) in cells co-expressing Nedd4 with
      CNrasGEF but not with CNrasGEFDelta2PY (t(0.5) approximately 14 h). CNrasGEF is
      also stabilized in cells co-expressing Nedd4(CS) or following treatment with
      lactacystin, indicating proteasomal degradation of this protein.
      Deletion/mutation of the CDC25 domain to abrogate Ras (or Rap-1) binding leads to
      impaired ubiquitination of CNrasGEF, suggesting that such binding is critical for
      ubiquitination. Treatment of cells with the cAMP analogue 8-bromo-cAMP does not
      affect the ability of CNrasGEF to bind Nedd4 nor its level of ubiquitination,
      suggesting that Ras binding per se and not its activation is the critical step in
      triggering ubiquitination of CNrasGEF. These results suggest that CNrasGEF is a
      substrate for Nedd4, which regulates its ubiquitination and stability in cells.

PMID- 11598135
TI  - Malonyl-CoA:anthocyanin 5-O-glucoside-6"'-O-malonyltransferase from scarlet sage
      (Salvia splendens) flowers. Enzyme purification, gene cloning, expression, and
      characterization.
AB  - The orange to blue coloration of flowers in nature is, in most cases, provided by
      anthocyanins, a class of plant flavonoids, many of which are modified by malonyl
      group(s). However, the identity of the enzyme catalyzing the malonylation
      reaction remains to be established. Here, we describe for the first time the
      purification, characterization, and cDNA cloning of an anthocyanin
      malonyltransferase from scarlet sage (Salvia splendens) flowers. The purified
      enzyme (termed Ss5MaT1) was a monomeric 50-kDa protein catalyzing the
      regiospecific transfer of the malonyl group from malonyl-CoA to the 6"'-hydroxyl
      group of the 5-glucosyl moiety of anthocyanins. Ss5MaT1 showed a k(cat) value of
      7.8 s(-1) at 30 degrees C and pH 7.0 for the malonylation of
      bisdemalonylsalvianin (pelargonidin 3-(6"-O-caffeyl-beta-glucopyranoside)-5-beta
      glucopyranoside) and K(m) values of 101 microm and 57 microm for
      bisdemalonylsalvianin and malonyl-CoA, respectively. p-Coumaric acid, which
      mimics an aromatic acyl group linked to the 3-glucosidic moiety of an anthocyanin
      substrate, was a competitive inhibitor with respect to the substrate. This
      strongly suggests that the presence of an aromatic acyl group at the 3-glucosidic
      moiety of anthocyanin is important for substrate recognition by the enzyme. On
      the basis of the partial amino acid sequences of the purified enzyme, we isolated
      a cDNA encoding Ss5MaT1. Ss5MaT1 consisted of 462 amino acids and shared motifs
      that are commonly found among members of a versatile plant acyltransferase
      family, which was recently shown to include numerous homologs of unknown
      biochemical functions. Northern blot analysis revealed that the transcripts of
      Ss5MaT1 were detected in petals, sepals, bracts, and red stems, in accordance
      with the pigment accumulation patterns. Phylogenetic analysis suggests that the
      aliphatic and aromatic acylations of anthocyanins are generally catalyzed by
      subfamily members of the plant acyltransferase family.

PMID- 11598136
TI  - Interaction between the G alpha subunit of heterotrimeric G(12) protein and Hsp90
      is required for G alpha(12) signaling.
AB  - The G alpha subunit of G(12) protein, one of the heterotrimeric G proteins,
      regulates diverse and complex cellular responses by transducing signals from the
      cell surface, presumably involving more than one downstream effector. Yeast two
      hybrid screening of a human testis cDNA library identified a large fragment of
      Hsp90 as a protein that interacted with G alpha(12). The interaction between G
      alpha(12) and Hsp90 was further substantiated by a co-immunoprecipitation
      technique. We have determined that Hsp90 is not required for the interaction of G
      alpha(12) with its binding partners, p115(RhoGEF) and the G beta subunit.
      Importantly, Hsp90 is required for G alpha(12)-induced serum response element
      activation, cytoskeletal changes, and mitogenic response. Closely related to G
      alpha(12), the G alpha(13) subunit did not interact with Hsp90 and did not
      require functional Hsp90 for serum response element activation. Thus, our results
      identify a novel signaling module of G alpha(12) and Hsp90.

PMID- 11598137
TI  - Peroxisome proliferator-activated receptor gamma ligands inhibit mitogenic
      induction of p21(Cip1) by modulating the protein kinase Cdelta pathway in
      vascular smooth muscle cells.
AB  - The cyclin-dependent kinase inhibitor p21(Cip1) is up-regulated in response to
      mitogenic stimulation in various cells. PPARgamma ligands troglitazone (TRO, 10
      microm) and rosiglitazone (RSG, 10 microm) attenuated the induction of p21(Cip1)
      protein by platelet-derived growth factor (PDGF) and insulin without affecting
      cognate mRNA levels in rat aortic smooth muscle cells (RASMC). The protein kinase
      Cdelta (PKCdelta) inhibitor rottlerin also blocked the induction of p21(Cip1)
      protein, whereas the conventional PKC isotype inhibitor Go 6976 had no effect.
      Kinetic studies using the protein synthesis inhibitor cycloheximide showed that
      TRO, RSG, and rottlerin shortened the half-life of p21(Cip1) protein. TRO, RSG,
      and rottlerin inhibited PDGF-induced expression of p21(Cip1), but they did not
      affect insulin-induced expression of p21(Cip1). Both ligands inhibited PKCdelta
      enzymatic activity in PDGF-stimulated RASMC but not in insulin-stimulated cells.
      Adenovirus-mediated overexpression of PKCdelta rescued the down-regulation of
      p21(Cip1) expression both by TRO and RSG in PDGF-treated RASMC. These data
      suggested that the PKCdelta pathway plays a critical role in PDGF-induced
      expression of p21(Cip1) in RASMC and may be the potential target for PPARgamma
      ligand effects. Src kinase-dependent tyrosine phosphorylation of PKCdelta was
      decreased substantially by TRO and RSG. Tyrosine phosphorylation and activation
      of c-Src in response to PDGF were unaffected by either PPARgamma ligand. Protein
      tyrosine-phosphatase inhibitors sodium orthovanadate and dephostatin prevented
      PPARgamma ligand effects on PKCdelta tyrosine phosphorylation and enzymatic
      activity. Both inhibitors also reversed PPARgamma ligand effects on p21(Cip1)
      expression in PDGF-treated RASMC. PPARgamma ligands enhanced protein-tyrosine
      phosphatase activity in RASMC, which may be the mechanism for decreased PKCdelta
      tyrosine phosphorylation and activity. PPARgamma ligands regulate p21(Cip1) at a
      post-translational level by blocking PKCdelta signaling and accelerating
      p21(Cip1) turnover.

PMID- 11598138
TI  - Post-transcriptional stimulation of the assembly and secretion of triglyceride
      rich apolipoprotein B lipoproteins in a mouse with selective deficiency of brown
      adipose tissue, obesity, and insulin resistance.
AB  - A mouse model of insulin resistance and its associated dyslipidemia was generated
      by crossing mice expressing human apolipoprotein B (apoB) with mice lacking only
      brown adipose tissue (BATless). On a high fat diet, male apoB/BATless mice became
      obese, hypercholesterolemic, hypertriglyceridemic, and hyperinsulinemic compared
      with control apoB mice. Fast performance liquid chromatography revealed increased
      triglyceride concentrations in intermediate density lipoprotein/low density
      lipoprotein (LDL) and reduced high density lipoprotein cholesterol
      concentrations. Inhibition of lipolysis by the drug, tetrahydrolipostatin,
      demonstrated that very low density lipoprotein-sized particles were initially
      secreted. Metabolic studies employing Triton WR-1339 and either [(3)H]glycerol or
      [(3)H]palmitate showed that the hypertriglyceridemia in apoB/BATless mice was due
      to the increased synthesis and secretion of triglyceride. Furthermore,
      lipoprotein lipase and hepatic lipase activities were not defective. ApoB was
      also secreted at increased rates in the apoB/BATless mice. Similar levels of apoB
      mRNA in apoB and apoB/BATless mice indicated that apoB secretion was regulated
      post-transcriptionally. LDL receptor mRNA was increased in the apoB/BATless mice,
      indicating that the observed increase in apoB-lipoprotein secretion was not due
      to their decreased reuptake. Finally, mRNA levels of the large subunit of
      microsomal triglyceride transfer protein, a required component for very low
      density protein assembly, were not different between apoB and apoB/BATless mice.
      This rodent model should prove useful in exploring mechanisms underlying the
      regulation of apoB secretion in the context of insulin resistance.

PMID- 11598139
TI  - Characterization of fortilin, a novel antiapoptotic protein.
AB  - Apoptosis is meticulously controlled in living organisms. Its dysregulation has
      been shown to play a key role in a number of human diseases, including
      neoplastic, cardiovascular, and degenerative disorders. Bcl-2 family member
      proteins and inhibitors of apoptosis proteins are two major negative regulators
      of apoptosis. We report here the characterization of novel antiapoptotic protein,
      fortilin, which we identified through yeast two-hybrid library screening.
      Sequence analysis of fortilin revealed it to be a 172-amino acid polypeptide
      highly conserved from mammals to plants. Fortilin is structurally unrelated to
      either Bcl-2 family member proteins or inhibitors of apoptosis proteins. Northern
      blot analysis showed the fortilin message to be ubiquitous in normal tissue but
      especially abundant in the liver, kidney, and small intestine. Western blot
      analysis using anti-fortilin antibody showed more extensive expression in
      cancerous cell lines (H1299, MCF-7, and A549) than in cell lines derived from
      normal tissue (HEK293). Immunocytochemistry using HeLa cells transiently
      expressing FLAG-tagged fortilin and immunohistochemistry using human breast
      ductal carcinoma tissue and anti-fortilin antibody both showed that fortilin is
      predominantly localized in the nucleus. Functionally, the transient
      overexpression of fortilin in HeLa cells prevented them, in a dose-dependent
      fashion, from undergoing etoposide-induced apoptosis. Consistently, U2OS cells
      stably expressing fortilin protected the cells from cell death induced by
      etoposide over various concentrations and durations of exposure. In addition,
      fortilin overexpression inhibited caspase-3-like activity as assessed by the
      cleavage of fluorogenic substrate benzyloxycarbonyl-DEVD-7-amido-4
      (trifluoromethyl)coumarin. Furthermore, the antisense depletion of fortilin from
      breast cancer cell line MCF-7 was associated with massive cell death. These data
      suggest that fortilin represents a novel antiapoptotic protein involved in cell
      survival and apoptosis regulation.

PMID- 11598140
TI  - Sensitivity of mammalian cells expressing mutant ubiquitin to protein-damaging
      agents.
AB  - There is convincing evidence from studies in yeast that a functional
      ubiquitin/proteasome pathway is required to degrade misfolded or oxidatively
      damaged proteins but for technical reasons, it has been difficult to perform
      comparable studies in mammalian cells. To investigate the possibility that the
      ubiquitin/proteasome pathway is cytoprotective for mammalian cells, we have
      introduced epitope-tagged wild-type ubiquitin or dominant-negative mutant
      versions of ubiquitin into mouse HT4 neuroblastoma cells. Cells expressing mutant
      versions of ubiquitin were found to be sensitive to cadmium, an agent that causes
      oxidative damage to cellular components, and to canavanine, an amino acid analog
      that generates misfolded proteins. The greatest sensitivity to canavanine was
      observed in cells expressing a mutant version of ubiquitin unable to support the
      formation of Lys(48) linkages. Substrates of the proteasome were found to
      accumulate in these cells, suggesting a general deficit in proteolysis. Our data
      suggest that defects in the ubiquitin-mediated proteolytic system predispose
      mammalian cells to the toxic effects of abnormal protein.

PMID- 11598141
TI  - Differential effects of phosphatidylinositol 3-kinase inhibition on intracellular
      signals regulating GLUT4 translocation and glucose transport.
AB  - Phosphatidylinositol (PI) 3-kinase is required for insulin-stimulated
      translocation of GLUT4 to the surface of muscle and fat cells. Recent evidence
      suggests that the full stimulation of glucose uptake by insulin also requires
      activation of GLUT4, possibly via a p38 mitogen-activated protein kinase (p38
      MAPK)-dependent pathway. Here we used L6 myotubes expressing Myc-tagged GLUT4 to
      examine at what level the signals regulating GLUT4 translocation and activation
      bifurcate. We compared the sensitivity of each process, as well as of signals
      leading to GLUT4 translocation (Akt and atypical protein kinase C) to PI 3-kinase
      inhibition. Wortmannin inhibited insulin-stimulated glucose uptake with an IC(50)
      of 3 nm. In contrast, GLUT4myc appearance at the cell surface was less sensitive
      to inhibition (IC(50) = 43 nm). This dissociation between insulin-stimulated
      glucose uptake and GLUT4myc translocation was not observed with LY294002 (IC(50)
      = 8 and 10 microm, respectively). The sensitivity of insulin-stimulated
      activation of PKC zeta/lambda, Akt1, Akt2, and Akt3 to wortmannin (IC(50) = 24,
      30, 35, and 60 nm, respectively) correlated closely with inhibition of GLUT4
      translocation. In contrast, insulin-dependent p38 MAPK phosphorylation was
      efficiently reduced in cells pretreated with wortmannin, with an IC(50) of 7 nm.
      Insulin-dependent p38 alpha and p38 beta MAPK activities were also markedly
      reduced by wortmannin (IC(50) = 6 and 2 nm, respectively). LY294002 or transient
      expression of a dominant inhibitory PI 3-kinase construct (Delta p85), however,
      did not affect p38 MAPK phosphorylation. These results uncover a striking
      correlation between PI 3-kinase, Akt, PKC zeta/lambda, and GLUT4 translocation on
      one hand and their segregation from glucose uptake and p38 MAPK activation on the
      other, based on their wortmannin sensitivity. We propose that a distinct, high
      affinity target of wortmannin, other than PI 3-kinase, may be necessary for
      activation of p38 MAPK and GLUT4 in response to insulin.

PMID- 11598142
TI  - Regulation of formyl peptide receptor agonist affinity by reconstitution with
      arrestins and heterotrimeric G proteins.
AB  - Although heptahelical chemoattractant and chemokine receptors are known to play a
      significant role in the host immune response and the pathophysiology of disease,
      the molecular mechanisms and transient macroassemblies underlying their
      activation and regulation remain largely uncharacterized. We report herein real
      time analyses of molecular assemblies involving the formyl peptide receptor
      (FPR), a well described member of the chemoattractant subfamily of G protein
      coupled receptors (GPCRs), with both arrestins and heterotrimeric G proteins. In
      our system, the ability to define and discriminate distinct, in vitro receptor
      complexes relies on quantitative differences in the dissociation rate of a
      fluorescent agonist as well as the guanosine 5'-3-O-(thio)triphosphate (GTP gamma
      S) sensitivity of the complex, as recently described for FPR-G protein
      interactions. In the current study, we demonstrate a concentration- and time
      dependent reconstitution of liganded, phosphorylated FPR with exogenous arrestin
      2 and -3 to form a high agonist affinity, nucleotide-insensitive complex with
      EC(50) values of 0.5 and 0.9 microm, respectively. In contrast, neither arrestin
      2 nor arrestin-3 altered the ligand dissociation kinetics of activated,
      nonphosphorylated FPR. Moreover, we demonstrated that the addition of G proteins
      was unable to alter the ligand dissociation kinetics or induce a GTP gamma S
      sensitive state of the phosphorylated FPR. The properties of the phosphorylated
      FPR were entirely reversible upon treatment of the receptor preparation with
      phosphatase. These results represent to our knowledge the first report of the
      reconstitution of a detergent-solubilized, phosphorylated GPCR with arrestins
      and, furthermore, the first demonstration that phosphorylation of a nonvisual
      GPCR is capable of efficiently blocking G protein binding in the absence of
      arrestin. The significance of these results with respect to receptor
      desensitization and internalization are discussed.

PMID- 11598143
TI  - Structure of a family 15 carbohydrate-binding module in complex with
      xylopentaose. Evidence that xylan binds in an approximate 3-fold helical
      conformation.
AB  - The recycling of photosynthetically fixed carbon by the action of microbial
      glycoside hydrolases is a key biological process. The consortium of degradative
      enzymes involved in this process frequently display catalytic modules appended to
      one or more noncatalytic carbohydrate-binding modules (CBMs). CBMs play a central
      role in the optimization of the catalytic activity of plant cell wall hydrolases
      through their binding to specific plant structural polysaccharides. Despite their
      pivotal role in the biodegradation of plant biomass, the mechanism by which these
      proteins recognize their target ligands is unclear. This report describes the
      structure of a xylan-binding CBM (CBM15) in complex with its ligand. This module,
      derived from Pseudomonas cellulosa xylanase Xyn10C, binds to both soluble xylan
      and xylooligosaccharides. The three-dimensional crystal structure of CBM15 bound
      to xylopentaose has been solved by x-ray crystallography to a resolution of 1.6
      A. The protein displays a similar beta-jelly roll fold to that observed in many
      other families of binding-modules. A groove, 20-25 A in length, on the concave
      surface of one of the beta-sheets presents two tryptophan residues, the faces of
      which are orientated at approximately 240 degrees to one another. These form
      stacking interactions with the n and n+2 sugars of xylopentaose complementing the
      approximate 3-fold helical structure of this ligand in the binding cleft of
      CBM15. In four of the five observed binding subsites, the 2' and 3' hydroxyls of
      the bound ligand are solvent-exposed, providing an explanation for the capacity
      of this xylan-binding CBM to accommodate the highly decorated xylans found in the
      plant cell wall.

PMID- 11598146
TI  - Tissue microarray profiling of cancer specimens and cell lines: opportunities and
      limitations.
AB  - The implementations of high-throughput genetic technologies, such as
      oligonucleotide microarrays, generate myriad points of data. The identified
      potential candidate genes need to be further characterized and selected using a
      large number of well-characterized tumors and stringent criteria. Tissue
      microarrays allow for such high-throughput expression profiling of tumor samples,
      providing, in addition, information at the microanatomical level. Different
      techniques could be applied for identification of specific phenotypic
      (immunohistochemistry and in situ hybridization) or genotypic (fluorescence in
      situ hybridization) alterations, holding strong potential for translational
      research. Tissue microarrays consisting of 0.6-mm biopsies of paraffin-embedded
      tissues are well validated and have been used for various clinicopathological
      studies. This review discusses the technical considerations for construction of
      such arrays from paraffin-embedded tissues and cell lines and outlines their
      potential for clinical research applications. The use of paraffin-embedded
      tissues has some limitations with regard to analysis of RNA or certain proteins.
      To overcome such limitations, we have developed a cryoarray strategy allowing for
      the processing of multiple frozen tissue specimens and/or cell lines on a single
      tissue block. These approaches offer the opportunity to conduct pilot and
      validation studies of potential targets using clinical samples linked to
      clinicopathological databases.

PMID- 11598144
TI  - The carboxyl-terminal domain of the granulocyte colony-stimulating factor
      receptor uncouples ribosomal biogenesis from cell cycle progression in
      differentiating 32D myeloid cells.
AB  - Translational regulation plays an important role in development. In terminally
      differentiating cells a decrease in translation rate is common, although the
      regulatory mechanisms are unknown. We utilized 32Dcl3 myeloblast cells to
      investigate translational regulation during granulocyte colony-stimulating factor
      (G-CSF)-induced differentiation. G-CSF causes a significant decrease in
      translation rate compared with interleukin-3, which is a mitogen for these cells.
      Although these two cytokines exhibit modest differences in their effect on
      translation factor phosphorylation, they exhibit dramatic differences in their
      effect on ribosomal abundance and ribosomal DNA transcription. However, because
      both cytokines stimulate cell cycling, G-CSF induces a dissociation of ribosomal
      biogenesis from cell cycle progression. This uncoupling of ribosomal biogenesis
      from cell cycle progression appears to be closely related to the transmission of
      a differentiation signal, because it is not observed in cells expressing a
      carboxyl-terminally truncated G-CSF receptor, which supports proliferation but
      not differentiation of these cells. Because a similar event occurs early in
      differentiation of murine erythroleukemic cells, this suggests that ribosomal
      content is a common target of differentiating agents.

PMID- 11598147
TI  - Clustering of colonic lamina propria CD4(+) T cells to subepithelial dendritic
      cell aggregates precedes the development of colitis in a murine adoptive transfer
      model.
AB  - Initial lesions in inflammatory bowel disease induced during the repopulation of
      immunodeficient RAG1(-/-) mice with immunocompetent CD4(+) T cells have not been
      previously described. In this transfer colitis model, we followed CD4(+) T cell
      repopulation in the host by injecting autofluorescent CD4(+) T cells from
      congenic, enhanced green fluorescent protein (eGFP)-transgenic mice. This allowed
      the direct, sensitive, and unambiguous histological detection of the repopulation
      of the intestinal tract, mesenteric lymph nodes, and spleen of the host with
      donor eGFP(+) CD4(+) T cells. We identified in RAG1(-/-) mice intestinal
      dendritic cell (DC) aggregates under the basal crypt epithelium at the
      mucosa/submucosa junction from which F4/80(+) macrophages were excluded. At Days
      8 to 11 posttransfer (before colitis was manifest), CD4(+) T cells clustered and
      proliferated in CD11c(+) DC aggregates. T cell clustering was most pronounced in
      the cecum where histologically overt colitis became manifest 5 to 10 days later.
      Junctional DC aggregates were thus prevalent in the triggering phase of the
      disease. The data suggest that pathogenic T cell responses inducing inflammatory
      bowel disease are primed or restimulated in situ in junctional CD4(+) T cell/DC
      aggregates.

PMID- 11598148
TI  - Transcription of cytokeratins 8, 18, and 19 in bone marrow and limited expression
      of cytokeratins 7 and 20 by carcinoma cells: inherent limitations for RT-PCR in
      the detection of isolated tumor cells.
AB  - The suitability of "real-time" quantitative reverse transcriptase polymerase
      chain reaction (RT-PCR) for the detection of isolated carcinoma cells in bone
      marrow was investigated by evaluating the expression of cytokeratin (CK)7, CK8,
      CK18, CK19, and CK20 in 17 gastrointestinal cancer cell lines, 64 control bone
      marrow specimens from noncancer patients, and 30 bone marrow specimens from
      patients with gastric or colorectal cancer. RT-PCR products for CK8 and CK18 were
      detected in all cancer cell lines, but only 16, 5, and 11 cell lines provided
      evidence for CK19, CK7, and CK20 transcription. Variable numbers of bone marrow
      specimens from noncancer patients demonstrated background transcription of CK8
      (78.1%), CK18 (95.3%), CK19 (35.9%), CK20 (29.6%), and CK7 (16.7%). Maximal
      background transcription for CK8, CK18, and CK19 ranged from 52.2 to 56.1
      copies/10(3) copies glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the
      corresponding values of 0.06 and 0.76 copies for CK7 and CK20 being distinctly
      lower. When maximal background values were used as a threshold value to define
      positivity in tumor cell dilution experiments, sensitivity levels of one tumor
      cell in 10(4) bone marrow cells were determined for CK7 and CK20 RT-PCR assays.
      Maximal background expression values of the different CKs as obtained in the
      control series were exceeded once (CK20), twice (CK18 and CK19), and 18 times
      (CK7) in bone marrow specimens from cancer patients, with none of these specimens
      exceeding the maximal background expression value of CK8. We conclude that RT-PCR
      for CK8, CK18, and CK19 cannot be recommended for the detection of isolated tumor
      cells in bone marrow of cancer patients. On the other side, the limited number of
      gastric and colorectal cancer cell lines expressing CK7 and CK20 indicates that
      assay sensitivity for these CKs might be limited because of their selective
      expression by carcinoma cells.

PMID- 11598149
TI  - Comparative genomic hybridization of microdissected familial ovarian carcinoma:
      two deleted regions on chromosome 15q not previously identified in sporadic
      ovarian carcinoma.
AB  - The vast majority of familial ovarian cancers harbor a germline mutation in
      either the breast cancer gene BRCA1 or BRCA2 tumor suppressor genes. However,
      mutations of these genes in sporadic ovarian cancer are rare. This suggests that
      in contrast to hereditary disease, BRCA1 and BRCA2 are not commonly involved in
      sporadic ovarian cancer and may indicate that there are two distinct pathways for
      the development of ovarian cancer. To characterize further differences between
      hereditary and sporadic cancers, the comparative genomic hybridization technique
      was employed to analyze changes in copy number of genetic material in a panel of
      36 microdissected hereditary ovarian cancers. Gains at 8q23-qter (18 of 36, 5
      cases with high-level amplifications), 3q26.3-qter (18 of 36, 2 cases with high
      level amplifications), 11q22 (11 of 36) and 2q31-32 (8 of 36) were most frequent.
      Losses most frequently occurred (in decreasing order of frequency) on 8p21-pter
      (23 of 36), 16q22-pter (19 of 36), 22q13 (19 of 36), 9q31-33 (16 of 36), 12q24
      (16 of 36), 15q11-15 (16 of 36), 17p12-13 (14 of 36), Xp21-22 (14 of 36), 20q13
      (13 of 36), 15q24-25 (12 of 36), and 18q21 (12 of 36). Comparison with the
      literature revealed that the majority of these genetic alterations are also
      common in sporadic ovarian cancer. Deletions of 15q11-15, 15q24-25, 8p21-ter,
      22q13, 12q24 and gains at 11q22, 13q22, and 17q23-25, however, appear to be
      specific to hereditary ovarian cancer. Aberrations at 15q11-15 and 15q24-25 have
      not yet been described in familial ovarian cancer. In these regions, important
      tumor suppressor genes, including the hRAD51 gene, are located. These and other
      yet unknown suppressor genes may be involved in a specific carcinogenic pathway
      for familial ovarian cancer and may explain the distinct clinical presentation
      and behavior of familial ovarian cancer.

PMID- 11598151
TI  - Early interleukin 4-dependent response can induce airway hyperreactivity before
      development of airway inflammation in a mouse model of asthma.
AB  - In experimental models of bronchial asthma with mice, airway inflammation and
      increase in airway hyperreactivity (AHR) are induced by a combination of systemic
      sensitization and airway challenge with allergens. In this report, we present
      another possibility: that systemic antigen-specific sensitization alone can
      induce AHR before the development of inflammation in the airway. Male BALB/c mice
      were sensitized with ovalbumin (OVA) by a combination of intraperitoneal
      injection and aerosol inhalation, and various parameters for airway inflammation
      and hyperreactivity were sequentially analyzed. Bronchial response measured by a
      noninvasive method (enhanced pause) and the eosinophil count and interleukin (IL)
      5 concentration in bronchoalveolar lavage fluid (BALF) gradually increased
      following the sensitization, and significant increase was achieved after repeated
      OVA aerosol inhalation along with development of histologic changes of the
      airway. In contrast, AHR was already significantly increased by systemic
      sensitization alone, although airway inflammation hardly developed at that time
      point. BALF IL-4 concentration and the expression of IL-4 mRNA in the lung
      reached maximal values after the systemic sensitization, then subsequently
      decreased. Treatment of mice with anti-IL-4 neutralizing antibody during systemic
      sensitization significantly suppressed this early increase in AHR. In addition,
      IL-4 gene-targeted mice did not reveal this early increase in AHR by systemic
      sensitization. These results suggest that an immune response in the lung in an
      early stage of sensitization can induce airway hyperreactivity before development
      of an eosinophilic airway inflammation in BALB/c mice and that IL-4 plays an
      essential role in this process. If this early increase in AHR does occur in
      sensitized human infants, it could be another therapeutic target for early
      prevention of the future onset of asthma.

PMID- 11598150
TI  - Interleukin-18 induces rheumatoid arthritis synovial fibroblast CXC chemokine
      production through NFkappaB activation.
AB  - Interleukin-18 (IL-18) is a novel proinflammatory cytokine that was recently
      found in synovial fluids and in synovial tissues from patients with rheumatoid
      arthritis (RA). To determine the participation of IL-18 in the inflammation
      observed in RA, we investigated the effect of IL-18 on RA synovial fibroblast
      chemokine production. Using FACS analysis, we showed that IL-18 induced a
      doubling in the production of intracellular IL-8 by RA synovial fibroblasts, and
      this result was confirmed by Western blot. At the extracellular level, IL-18 up
      regulated the secretion of IL-8 in a dose- and time-dependent manner. IL-18 also
      up-regulated the other CXC chemokines, epithelial-neutrophil activating protein
      (ENA-78) and growth-regulated oncogene (groalpha), in a dose dependent manner,
      but failed to induce the production of the CC chemokine, macrophage inflammatory
      protein (MIP)-1alpha. By immunofluorescence and Western blot, we demonstrated
      that IL-18 activates the translocation of the transcription factor nuclear factor
      kappa B (NFkappaB) into the nucleus of RA synovial fibroblasts. IL-18 induces IL
      8 secretion through NFkappaB because RA synovial fibroblasts pretreated with
      antisense to NFkappaB p65 oligonucleotide produce a mean of 44% less IL-8
      compared with cells pretreated with the control sense oligonucleotide. These
      results indicate a novel role for IL-18 in inducing RA synovial fibroblast
      expression of CXC chemokines through NFkappaB and place this cytokine in a
      strategic role in the local inflammation observed in RA.

PMID- 11598152
TI  - Allelic loss detection in inflammatory breast cancer: improvement with laser
      microdissection.
AB  - Solid tumors are composed not only of tumor cells but also of stromal
      nonneoplastic cells. In whole tumor samples, stromal cells retaining their
      alleles may therefore obscure detection of loss of heterozygosity (LOH) in tumor
      cells. An increasing number of studies have used laser-assisted tissue
      microdissection to improve LOH detection, but the real gain in sensitivity has
      been poorly quantified. We studied a group of 16 inflammatory breast carcinomas
      that were submitted to both standard DNA extraction from frozen whole tumor
      samples and laser microdissection performed on paraffin-embedded tumor samples.
      Using PCR with fluorescence-labeled primers, we comparatively analyzed ten
      polymorphic markers with both sources of DNA. With the LOH detection threshold
      set at -25%, we showed that 25 LOHs could not be diagnosed with whole tumor
      samples out of 73 LOHs positively diagnosed in microdissected samples (34%). With
      the LOH detection threshold set at -50%, the respective figures were 39 LOHs not
      diagnosed out of 55 LOHs (71%). Measuring the intensity of the allelic decrease,
      we showed that the mean decrease of the lost allele is -34% with whole tumor
      samples and -67% with microdissected samples. The increase in sensitivity of LOH
      detection with microdissection is associated with the density of stromal cells.
      This strong improvement in LOH detection in this aggressive type of breast cancer
      indicates that many other molecular studies performed on heterogeneous solid
      tumors may benefit from a first step of laser microdissection.

PMID- 11598153
TI  - The urokinase plasminogen activator receptor-associated protein/endo180 is
      coexpressed with its interaction partners urokinase plasminogen activator
      receptor and matrix metalloprotease-13 during osteogenesis.
AB  - The urokinase plasminogen activator receptor-associated protein/Endo180
      (uPARAP/Endo180) is a newly discovered member of the macrophage mannose receptor
      family that was reported to interact with ligand-bound urokinase plasminogen
      activator receptor (uPAR), matrix metalloprotease-13 (MMP-13), and collagen V on
      the cell surface. We have determined the sites of expression of this novel
      receptor during murine postimplantation development. uPARAP/Endo180 was expressed
      in all tissues undergoing primary ossification, including the developing bones of
      the viscerocranium and calvarium that ossify intramembranously, and developing
      long bones undergoing endochondral ossification. uPARAP/Endo180 mRNA was
      expressed by both immature osteoblasts and by mature osteocalcin-producing
      osteoblasts-osteocytes, and was coexpressed with MMP-13. Interestingly,
      osteoblasts also expressed uPAR. Besides bone-forming tissues, uPARAP/Endo180
      expression was detected only in a mesenchymal condensation of the midbrain and in
      the developing lungs. The data suggest a function of this novel protease receptor
      in bone development, possibly mediated through its interactions with uPAR, MMP
      13, or collagen V.

PMID- 11598154
TI  - Peptide nucleic acids and biosensor technology for real-time detection of the
      cystic fibrosis W1282X mutation by surface plasmon resonance.
AB  - In this paper we demonstrate that peptide nucleic acids (PNAs) are excellent
      probes able to detect the W1282X point mutation of the cystic fibrosis (CF) gene
      when biospecific interaction analysis (BIA) by surface plasmon resonance (SPR)
      and biosensor technologies is performed. The results reported here suggest that
      BIA is an easy, fast, and automatable approach for detecting mutations of CF,
      allowing real-time monitoring of hybridization between 9-mer CF PNA probes and
      target biotinylated PCR products generated from healthy, heterozygous subjects
      and homozygous W1282X samples and immobilized on streptavidin-coated sensor
      chips. This method is, to our knowledge, the first application of PNAs, BIA, and
      SPR to a human hereditary mutation, and demonstrates the feasibility of these
      approaches for discriminating between normal and mutated target DNA. We like to
      point out that the procedure described in this paper is rapid and informative;
      results are obtained within a few minutes. This could be of great interest for
      molecular pre-implantation diagnosis to discriminate homozygous CF embryos from
      heterozygous and healthy embryos. Other advantages of the methodology described
      in the present paper are (a) that it is a nonradioactive methodology and (b) that
      gel electrophoresis and/or dot-spot analysis are not required. More importantly,
      the demonstration that SPR-based BIA could be associated with microarray
      technology allows us to hypothesize that the method described in the present
      paper could be used for the development of a protocol employing multispotting on
      SPR biosensors of many CF-PCR products and a real-time simultaneous analysis of
      hybridization to PNA probes. These results are in line with the concept that SPR
      could be an integral part of a fully automated diagnostic system based on the use
      of laboratory workstations, biosensors, and arrayed biosensors for DNA isolation,
      preparation of PCR reactions, and identification of point mutations.

PMID- 11598155
TI  - Frequent allelic imbalance and loss of protein expression of the DNA repair gene
      hOGG1 in head and neck squamous cell carcinoma.
AB  - Reactive oxygen species produced by aerobic cellular metabolism or through
      exposure to environmental carcinogens can cause oxidative DNA damage by
      generating DNA base lesions and strand breakage. Prime among these base lesions
      is the conversion of guanine to 8-oxoguanine. Among 20 or so oxidative DNA base
      lesions, 8-oxoguanine is the most abundant and is critical in terms of
      mutagenesis because it is capable of mispairing with adenine, which, if not
      sufficiently repaired, may lead to G:C to T:A transversion upon DNA replication.
      The gene encoding human 8-oxoguanine DNA glycosylase 1 (hOGG1), capable of
      excision repair of 8-oxoguanine, has been recently cloned, characterized, and
      mapped to the short arm of chromosome 3 (3p25-26), a region showing frequent loss
      of heterozygosity (LOH) in head and neck squamous cell carcinoma (HNSCC). In the
      present study, we developed a tissue microdissection approach designed for use
      with formalin-fixed, paraffin-embedded specimens which is capable of detecting
      and characterizing the hOGG1 allelic loss using two highly informative,
      intragenic single nucleotide polymorphisms. Among 45 cases of HNSCC, 18 cases
      were informative. We analyzed these 18 cases and found that 11 showed evidence of
      hOGG1 allelic loss. By immunohistochemical staining on a total of 71 HNSCC cases
      using a commercially available anti-hOGG1 antibody, we showed that hOGG1 gene
      expression was markedly suppressed in up to 38% of the cases. The frequent
      allelic imbalance and suppression of the hOGG1 gene thus imply that repair for
      oxidative DNA damages may be relevant in future studies on head and neck squamous
      carcinogenesis.

PMID- 11598157
TI  - Detection of microsatellite instability by real time PCR and hybridization probe
      melting point analysis.
AB  - Microsatellite alterations can be found in a number of tumors. There are two
      types of alterations: loss of heterozygosity (LOH), which can be detected in the
      majority of colorectal cancers (CRC), and microsatellite instability (MSI). MSI
      occurs in about 15% of CRC with a mutator phenotype and are the hallmark of
      hereditary nonpolyposis colorectal cancers (HNPCC). Furthermore, MSI can also be
      detected in other tumors which are part of the HNPCC tumor spectrum (eg, gastric,
      ovarian, and endometrial carcinomas). Usually, a set of microsatellite markers is
      amplified by PCR followed by gel or capillary electrophoresis to separate PCR
      amplicons and by detection of the markers using autoradiography (Thibodeau et al,
      1993), silver staining (Schlegel et al, 1996), or fluorescence techniques (Gyapay
      et al, 1996; Mansfield et al, 1994). We have established a technique to detect
      MSI by LightCycler PCR and melting point analysis using sequence-specific
      hybridization probes (HyProbes) labeled with LightCycler dyes, LCRed640 and
      LCRed705. Amplification of microsatellites by real-time PCR is followed by
      melting point analysis to display alterations in the length of repetitive
      sequences, thereby avoiding any electrophoretical separation of amplified DNA.
      Two mononucleotide markers (BAT25 and BAT26) were tested in 81 formalin-fixed and
      paraffin-embedded colorectal cancer samples with matched normal tissues from 21
      MSI tumors and 60 tumors with microsatellite stability. Amplification and melting
      point determination of BAT26 and BAT25 was possible in 129/162 (80%) and 123/162
      (76%) formalin-fixed and paraffin-embedded tissue samples, respectively. MSI
      could be detected specifically with both BAT25 and BAT26 markers only in MSI-high
      tumors (> or =40% MSI rate, determined with microsatellite reference panel,
      BAT25, BAT26, D5S346, D2S123, D17S250; Boland et al, 1998; Dietmaier et al,
      1997). This new technique allows MSI detection within less than a hour and
      provides a basis for fast, high-throughput MSI analysis.

PMID- 11598156
TI  - Pancreas microenvironment promotes VEGF expression and tumor growth: novel window
      models for pancreatic tumor angiogenesis and microcirculation.
AB  - Pancreatic cancer has a poor prognosis, and treatment strategies based on
      preclinical research have not succeeded in significantly extending patient
      survival. This failure likely stems from the general lack of information on
      pancreatic tumor physiology, attributable to the difficulties in developing
      relevant, orthotopic models that accurately reflect pancreatic cancer in the
      clinic. To overcome this limitation, we developed abdominal wall windows suitable
      for intravital microscopy that allowed us to monitor angiogenesis and
      microvascular function noninvasively during tumor growth in vivo. We used two
      complementary tumor models in mice: orthotopic (human ductal pancreatic
      adenocarcinoma, PANC-1, grown in the pancreas), and ectopic (PANC-1 grown in the
      abdominal wall). We found that orthotopic PANC-1 tumors grew faster than the
      ectopic tumors and exhibited metastatic spread in the late stage similar to
      advanced pancreatic cancer in the clinic. Orthotopic PANC-1 tumors expressed
      vascular endothelial growth factor (VEGF)(121) and VEGF(165), contained higher
      levels of tumor cell-derived VEGF protein, and maintained vascular density and
      hyperpermeability during exponential tumor growth. Orthotopic PANC-1 tumors
      showed lower leukocyte-endothelial interactions in the early stage of growth. In
      addition, both VEGF(121) and VEGF(165) promoted the growth of PANC-1 cells in
      vitro. Finally, Anti-VEGF neutralizing antibody inhibited angiogenesis and tumor
      growth of PANC-1 tumors in both sites. We conclude that the orthotopic pancreas
      microenvironment enhances VEGF expression, which stimulates growth of PANC-1
      tumors (compared with ectopic tumors). The mechanism is autocrine and/or
      paracrine and also is involved in the maintenance of blood vessels. This
      comparative system of orthotopic and ectopic pancreatic cancer will provide the
      rigorous understanding of pancreatic tumor pathophysiology needed for development
      of novel therapeutic strategies.

PMID- 11598158
TI  - Sequential multilocus fluorescence in situ hybridization can detect complex
      patterns of increased gene dosage at the single cell level in tissue sections.

PMID- 11598159
TI  - A novel method for isolating pure microvascular endothelial cells from
      subcutaneous fat tissue ideal for direct cell seeding.

PMID- 11598160
TI  - Chemokine gene expression and clonal analysis of B cells in tissues involved by
      lymphoid interstitial pneumonitis from HIV-infected pediatric patients.
AB  - Lymphoid interstitial pneumonitis (LIP), a frequent pulmonary complication in HIV
      infected pediatric patients, is characterized histologically by marked
      infiltration of lymphoid cells. We sought to evaluate the nature and pathogenesis
      of the lymphoid infiltrates and to examine the relationship of LIP to pulmonary
      MALT lymphoma that has been described in pediatric HIV positive patients. To
      examine the potential contribution of chemokines and cytokines to the
      inflammatory cell recruitment in tissues involved by lymphoid interstitial
      pneumonitis from HIV-infected pediatric patients, RNA was extracted from paraffin
      embedded tissues from five lung biopsies in four pediatric HIV-positive patients
      and from five control, normal lung biopsies in five HIV-negative patients and was
      analyzed by semiquantitative RT-PCR for the expression of cytokines (TNF-alpha,
      GM-CSF, IFN-gamma, IL-4, IL-6, IL-10, and IL-18) and chemokines (IP-10, Mig,
      regulated upon activation, normal T expressed and secreted [RANTES], and MIP1
      alpha and beta) after normalization for G3PDH. Expression of IL-18 was increased,
      as well as expression of IFN-gamma-inducible chemokines IP-10 and Mig in LIP
      tissues compared with controls. RANTES and MIP1-alpha and -beta were also
      increased in pediatric LIP lesions compared with controls. In contrast,
      expression of TNF-alpha, GM-CSF, IL-10, and IL-6 was variable in LIP tissues and
      controls. In addition, clonality of the B-cell population was evaluated by VDJ
      PCR. A polyclonal B-cell population was shown in all five biopsies from five
      patients with LIP; and in one patient with concurrent LIP and MALT lymphoma, a
      band of increased intensity was observed in the LIP biopsy that was identical in
      size to the monoclonal band in the concurrent MALT lymphoma biopsy. These results
      provide evidence of high-level expression of certain chemokines in lymphoid
      interstitial pneumonitis tissues and suggest that chemokines and cytokines may
      play an important role in the recruitment of inflammatory cell infiltrates into
      these tissues. In addition, LIP may represent an early stage of MALT lymphoma or
      an immunologic response to a chronic antigenic stimulus that may provide a milieu
      or microenvironment for the evolution of a monoclonal B-cell population.

PMID- 11598161
TI  - Correlation of nuclear morphometry with pathologic parameters in ductal carcinoma
      in situ of the breast.
AB  - Morphometric features of nuclear perimeter, nuclear area, feret ratio, and feret
      circle were studied in a series of 64 cases of ductal carcinoma in situ (DCIS) of
      the breast in Singapore women. The results were compared with pathologic
      parameters of tumor size, nuclear grade, necrosis, cell polarization, and
      architectural pattern. There was statistically significant correlation between
      nuclear perimeter and area with all the pathologic parameters, with the strongest
      association observed for nuclear grade (P <.0001). Higher grade nuclei as
      assessed histologically were associated with larger nuclear area (44.14 microm(2)
      in low-grade lesions, 47.77 microm(2) in intermediate-grade lesions, and 72.05
      microm(2) in high-grade lesions) and perimeter (25.94 microm in low-grade nuclei,
      27.12 microm in intermediate-grade nuclei, and 33.66 microm in high-grade
      nuclei). DCIS lesions with necrosis and absence of polarization also revealed
      increased nuclear area and perimeter (P <.05). Comedo architecture was associated
      with larger nuclear area and perimeter (65.97 microm(2), 31.7 microm) than the
      papillary subtype (42.17 microm(2), 25.29 microm), with the mixed morphologic
      pattern disclosing intermediate values (54.83 microm(2), 29.43 microm). There was
      direct correlation for tumor size with nuclear area and perimeter (P <.01). No
      similar relationship was found between pathologic parameters and feret ratio or
      circle, indicating that nuclear roundness or lack of it did not factor as a
      significant component in the pathologic assessment.

PMID- 11598162
TI  - Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer.
AB  - Loss of the cell adhesion molecule E-cadherin has been observed in a variety of
      human carcinomas, and germline E-cadherin mutations have been found in several
      familial cases of diffuse gastric cancer. We sought to determine the prevalence
      and nature of E-cadherin alterations in "sporadic" gastric carcinomas. We
      performed comprehensive sequencing of the coding region, loss of heterozygosity
      (LOH) analysis, and immunohistochemical protein expression determination on 40
      sporadic gastric adenocarcinomas. In total, 7 of 25 diffuse-type cancers harbored
      genetic alterations in the E-cadherin gene. Novel mutations predicted to
      significantly compromise protein function were found within 4 of these cancers, 2
      of which harbored alterations resulting in biallelic inactivation of the gene
      product. Three diffuse cancers failed to amplify Exon 8 of E-cadherin, suggesting
      the presence of a homozygous abnormality. Notably, one germline E-cadherin
      mutation was also identified within these "sporadic" diffuse cancers. Significant
      gene mutations were not found in the 14 intestinal-type or histologically mixed
      cancer. Immunohistochemistry revealed aberrant or negative protein expression in
      seven diffuse-type tumors, four of which correlated with the genetic alterations.
      Both diffuse and intestinal-type tumors exhibited low rates of LOH, suggesting
      that allelic loss at the locus is not a common mechanism for E-cadherin
      inactivation during gastric tumorigenesis. Our observations suggest that
      inactivation of the E-cadherin gene occurs only in a subset of diffuse-type
      gastric cancers, as the majority of cases did not contain genetic alterations or
      identifiable protein abnormalities. Germline E-cadherin alterations, although
      rare, may underlie some diffuse gastric cancer cases that have important biologic
      and practical implications

PMID- 11598163
TI  - Mesenchymal tumors of muscularis mucosae of colon and rectum are benign
      leiomyomas that should be separated from gastrointestinal stromal tumors--a
      clinicopathologic and immunohistochemical study of eighty-eight cases.
AB  - Most mesenchymal tumors of the gastrointestinal tract are currently classified as
      specific gastrointestinal stromal tumors. However, true leiomyomas are more
      common in the esophagus, and they have been occasionally noted in the colon and
      rectum, but the small number of reported cases does not allow for
      clinicopathologic profiling. This study was undertaken to characterize 88 tumors
      of the muscularis mucosae of the colon and rectum. Seventy tumors were obtained
      form the files of AFIP and 18 cases from the Department of Pathology of the
      Haartman Institute of the University of Helsinki. The lesions, except one, were
      removed by snare polypectomy as incidental lesions at cancer or polyp
      surveillance; one small tumor was an incidental finding in the rectal resection
      specimen. The tumors had a significant male predominance in both institutions
      (overall 2.4:1). They occurred in age range of 38 to 85 years (median 62 years).
      The lesions were typically small (range 1 to 22 mM, median 4 mM) and located
      predominantly in the rectum and sigmoid (72%). All tumors were composed of well
      differentiated, eosinophilic smooth muscle cells that were seen immediately
      beneath the mucosa obliterating the muscularis mucosae layer and merging with it.
      Two tumors had significant atypia ("symplastic leiomyoma"); mitotic activity was
      seen in one of these tumors, but not in others. The lesional cells were uniformly
      positive for smooth muscle actin and desmin and negative for CD34, CD117 and S100
      protein, based on immunohistochemical studies on 20 to 24 cases with each marker.
      No gastrointestinal stromal tumors were identified among the tumors of muscularis
      mucosae, and no CD117-positive cells, except mast cells, were seen in the
      muscularis mucosae layer. None of the patients had morbidity related to the
      tumor. Based on follow-up data on 29 patients, leiomyomas of muscularis mucosae
      are benign. They should be separated from gastrointestinal stromal tumors that
      have a clinicopathologic spectrum including frequent disease-related mortality.
      Snare polypectomy is an adequate treatment, but ensuring the complete removal and
      follow-up are necessary precautions for tumors with any atypia or mitotic
      activity.

PMID- 11598164
TI  - Clonal evolution of gastric lymphoma of mucosa-associated lymphoid tissue type.
AB  - Development of multiple lesions is frequent in gastric lymphoma of mucosa
      associated lymphoid tissue (MALT) type. Presence of clonal components in multiple
      lesions was examined on the resected samples from 18 cases by using PCR-based
      method for immunoglobulin heavy-chain gene rearrangement. There were two or more
      lesions in 10 cases, and 2 to 12 samples were obtained from each lesion. The
      remaining eight cases had a single large lesion, from which two to six samples
      were collected from separate areas from each other. A total of 86 samples were
      analyzed. Histologic findings in each sample were categorized as follows:
      proliferation of exclusively centrocyte-like cells (CCL), large cells, and
      combined CCL and large cells. Monoclonal or biclonal pattern (single or two
      bands) was observed in 42 samples, oligoclonal pattern (three or more bands) in
      30, polyclonal (smear) in 11, and no products in 3. Large-cell-type lesions
      showed fewer bands than those with other histologic types, and 75% of cases with
      large-cell type had mono- or biclonal proliferation. Common clones were found
      among lesions in about 60% of cases. Especially in 4 cases including 2 cases with
      large-cell type, every lesion in the same case contained the common clones. These
      findings suggested that gastric MALT lymphoma started as multi- or oligoclonal
      proliferation of cells, in which separate lesions composed of different clones
      from each other. As disease advances, dominant clones appear in some lesion and
      disseminate to other lesions via homing properties of the proliferating B
      lymphocytes.

PMID- 11598165
TI  - Predicting cancer progression in patients with penile squamous cell carcinoma:
      the importance of depth of invasion and vascular invasion.
AB  - The ability to predict cancer progression may help the clinical management of
      patients with penile squamous cell carcinoma. We studied 22 cases of squamous
      cell carcinoma of the penis diagnosed between 1989 and 1998. The depth of
      invasion was measured from the basement membrane of the squamous epithelium to
      the deepest invasive cancer cells. Cancer progression was defined as the
      development of lymph node metastasis or distant metastasis. The mean patient age
      was 63 years and the mean follow-up was 28 months. Ten patients developed cancer
      progression. The mean depth of invasion among patients with cancer progression
      was 9.8 mM, as compared to the mean depth of invasion of 4.0 mM among those
      patients without cancer progression (P =.02). Vascular invasion was also
      predictive of cancer progression (P =.02). Metastases developed in the majority
      (6 out of 7) of cases invading more than 6 mM, but developed only in a minority
      (4 out of 15) of cases invading 6 mM or less. We conclude that depth of invasion
      and vascular invasion are significant predictors of cancer progression for penile
      squamous cell carcinoma.

PMID- 11598166
TI  - Orthopaedic implant-related sarcoma: a study of twelve cases.
AB  - Sarcoma developing in association with a metallic orthopaedic prosthesis or
      hardware is an uncommon, but well recognized complication. We review 12 cases of
      sarcomas arising in bone or soft tissue at the site of orthopaedic hardware or a
      prosthetic joint. Nine patients were male, and three were female. Their ages
      ranged from 18 to 85 (mean 55) years at the time of diagnosis of the malignancy.
      Five patients had undergone hip arthroplasty for degenerative joint disease, four
      had been treated with intramedullary nail placement for fracture, two had staples
      placed for fixation of osteotomy, and one had hardware placed for fracture
      fixation followed years later by a hip arthroplasty. The time interval between
      the placement of hardware and diagnosis of sarcoma was known in 11 cases and
      ranged from 2.5 to 33 (mean 11) years. The patients presented with pain,
      swelling, or loosening of hardware and were found to have a destructive bone or
      soft tissue mass on radiography. Two sarcomas were located primarily in the soft
      tissue and 10 in bone. Seven patients developed osteosarcoma, four malignant
      fibrous histiocytoma, and one a malignant peripheral nerve sheath tumor. All
      sarcomas were high grade. Three patients had metastatic disease at the time of
      diagnosis. Follow-up was available on eight patients: five patients died of
      disease 2 months to 8 years (mean 26 months) after diagnosis; two patients died
      without evidence of disease 7 and 30 months after diagnosis; and one patient is
      alive and free of disease 8 years after diagnosis. Sarcomas that occur adjacent
      to orthopaedic prostheses or hardware are of varied types, but are usually
      osteosarcoma or malignant fibrous histiocytoma. They behave aggressively and
      frequently metastasize. Clinically, they should be distinguished from non
      neoplastic reactions associated with implants, such as infection and a reaction
      to prosthetic wear debris.

PMID- 11598167
TI  - Primary soft tissue sarcoma and its local recurrence: genetic changes studied by
      comparative genomic hybridization.
AB  - The aims of this study were to compare genetic aberrations in primary soft-tissue
      sarcomas and their local recurrences and to evaluate the genetic changes
      occurring during tumor progression. A primary soft-tissue sarcoma and its
      subsequent local recurrence were analyzed in 20 tumor pairs by comparative
      genomic hybridization. The samples were obtained before application of radio- or
      chemotherapy. Copy number aberrations were detected in 50% of the primary tumors
      and in 70% of the local recurrences. In primary tumors, the mean number of
      changes was 2.45 (range, 0 to 11) whereas in local recurrences, it was 5.05
      (range, 0 to 17). The mean increase of changes from primary tumor to local
      recurrence was 2.6 per tumor pair (P =.02). Gains predominated over losses in
      both primary tumors and their local recurrences. The number of high-level
      amplifications was twofold in local recurrences. The most frequent gain affected
      5p14-p15.1 (10% of primary tumors, 25% of local recurrences) and the most
      frequent loss, 9p (9p21-pter in 5% of primary tumors; 9p22-pter in 30% of local
      recurrences). In conclusion, our results show an increase in the number of
      genetic changes in local recurrences, due to tumor progression. Loss at 9p and
      gains at 5p and 20q were more frequent in local recurrences, and high-level
      amplification of 18p11.3 was not detected in any of the primary tumors. Although
      all these alterations were not specific to local recurrences, they may represent
      changes important during tumor progression.

PMID- 11598168
TI  - Clinicopathologic and DNA cytometric analysis of carcinoid tumors of the thymus.
AB  - Twelve cases of carcinoid tumors of the thymus were reviewed in terms of
      clinicopathologic, histochemical, and immunohistochemical features and DNA ploidy
      patterns. The collective consisted of nine male and three female patients, aged
      34 to 74 years, of whom five (42%) had symptoms. Eleven patients underwent
      surgical resection, and one with systemic metastases was autopsied. In the 11
      resected patients, tumors had invaded surrounding structures in four cases, and
      mediastinal lymph node metastases were detected in six. Recurrence occurred in
      two of the resected patients (18%), and the 5-year survival rate was 82%.
      Histologically, all tumors showed an organoid growth pattern with delicate
      fibrovascular stroma. In addition, three tumors had unusual morphologic features
      such as combined features of carcinoid tumor and thymoma and solid growth pattern
      with occasional large tumor cells. Mitotic counts ranged from 1 to 14 per 10 high
      power fields with a mean count of 4.9. Central necrosis within solid nests was
      observed in nine tumors. Classification of this series using the WHO histologic
      classification system resulted in categorization of all 12 tumors as atypical
      carcinoids. All tumors were positive for Grimelius staining and for cytokeratin.
      Immunohistochemical staining documented the presence of moderately to strongly
      positive neuroendocrine markers such as neuron-specific enolase, chromogranin A,
      synaptophysin, and neural cell adhesion molecule. No correlation between
      proliferative activity based on the Ki67 labeling index and prognosis or lymph
      node metastasis was found. Concerning DNA ploidy patterns, only one tumor with
      multiple lymph node metastases was considered to be aneuploid. In conclusion,
      although all of our cases were histologically classified as atypical carcinoid
      tumors of the thymus, most were diploid, and the patients enjoyed a relatively
      good prognosis.

PMID- 11598169
TI  - Detection of Toxoplasma gondii DNA in primary intraocular B-cell lymphoma.
AB  - Primary intraocular lymphoma, a variant of primary central nervous system
      lymphoma with ocular involvement, is a large B-cell non-Hodgkin's lymphoma. Some
      cases of primary intraocular lymphoma have been reported to be associated with
      microorganisms including Epstein-Barr virus (EBV) and human herpes virus-8 (HHV
      8), but not parasites. We analyzed 10 cases of primary intraocular lymphoma using
      microdissection and PCR. Tumor and normal cells were microdissected from ocular
      tissue on slides and subjected to PCR for genes from Toxoplasma gondii, EBV, and
      HHV-8. We detected Toxoplasma gondii, not HHV-8 or EBV, DNA in the lymphoma but
      not in normal cells of two cases that resembled ocular toxoplasmosis clinically.
      We speculate that Toxoplasma gondii may play a role in some forms of primary
      intraocular B-cell lymphoma.

PMID- 11598170
TI  - An immunophenotypic and molecular study of primary large B-cell lymphoma of bone.
AB  - Primary non-Hodgkin's lymphomas of bone (PNHLB) is a rare form of extranodal
      lymphoma. Many studies have reported the clinical, radiologic, and
      histopathologic characteristics of PNHLB; however, their molecular features have
      not been well studied. In this report, we present the immunophenotypic and
      molecular characteristics of 20 primary large B-cell lymphoma (PLBCL) of bone
      from 20 adults. Most demonstrated centroblastic morphology, with the majority
      exhibiting nuclear multilobation. One case (5%) demonstrated anaplastic features
      with strong CD30 expression but was ALK-1 negative. BCL-6 expression was seen in
      6 of 20 cases, and strong p53 protein expression was seen in 11 of 20 (55%)
      cases. The majority of cases analyzed (13/18 = 72%) demonstrated a clonal B-cell
      process by IgH gene rearrangement studies. Of the five cases that did not
      demonstrate a clonal population, two expressed BCL-6 protein. No cases
      demonstrated a bcl-2/JH rearrangement, but BCL-2 protein expression was seen in
      11 of 20 (55%) cases. In summary, primary lymphoma of bone is largely a non
      Hodgkin's lymphoma of large B-cell type. Our studies demonstrate that p53 and BCL
      2 expression may play a role in the pathogenesis of PLCBL of bone. In addition, a
      subset of the cases are of putative germinal center B-cell origin based on the
      expression of BCL-6 protein and may be genetically distinct from follicle center
      lymphomas. The results provide evidence for molecular heterogeneity within
      primary large B-cell lymphomas of bone.

PMID- 11598171
TI  - Prognostic significance of p27 and Ki-67 expression in mucoepidermoid carcinoma
      of the intraoral minor salivary gland.
AB  - p27 and Ki-67, a universal cyclin-dependent kinase inhibitor and a proliferative
      cell marker, respectively, have been useful in predicting clinical aggressiveness
      in various human tumors. We studied clinicopathologic significance of these
      molecules in mucoepidermoid carcinoma of the intraoral minor salivary gland.
      Expression of p27 and Ki-67 was assessed immunohistochemically in primary
      mucoepidermoid carcinomas from 31 patients without distant metastasis at surgery.
      Correlation each of p27 and Ki-67 expression was analyzed with various
      clinicopathologic parameters including age, sex, primary tumor site, tumor size,
      nodal metastasis, clinical stage, and histologic grade. The latter was evaluated
      using a point-scoring scheme of Auclair et al. that consists of five histologic
      factors (intracystic component, neural invasion, necrosis, mitosis, and
      anaplasia). p27 expression was correlated inversely with histologic grade (P
      =.007), but with none of other factors. When the correlation of p27 expression
      was further examined with each of the histologic factors, it was correlated
      significantly with intracystic component, but not with neural invasion, necrosis,
      mitosis, or anaplasia. Ki-67 expression was correlated significantly with
      histologic grade only in the clinicopathologic factors (P <.0001), and in the
      histologic factors, with necrosis, mitosis, and anaplasia. Multivariate
      prognostic analyses were performed to identify independent risk factors for both
      disease-free and overall survivals. Large tumor size (P =.031, relative risk =
      5.5) and low p27 expression (P =.012, relative risk = 5.2) were risk factors for
      worse disease-free survival. Low p27 expression (P =.015, relative risk = 15.2)
      was selected as a risk factor for worse overall survival. Other factors including
      age, sex, tumor site, nodal status, clinical stage, histologic grade, and Ki-67
      did not emerge as independent risk factors in either prognostic analysis. These
      data suggest that p27 may be useful in estimating prognosis of the patients who
      have mucoepidermoid carcinoma of the intraoral minor salivary gland.

PMID- 11598172
TI  - A novel multiparametric approach for analysis of cytoplasmic immunoglobulin light
      chains by flow cytometry.
AB  - We describe a novel flow cytometric approach using a two-step acquisition
      technique to determine the cytoplasmic immunoglobulin light chains (LC)
      expression. Samples were prepared by a lysed-whole-blood technique and incubated
      with CD38-PE (phycoerythrin) and CD45-FITC (fluorescein isothiocyanate). The
      cells were fixed and acquired on an FACSCalibur flow cytometer (first
      acquisition). The cells were then permeabilized, incubated with either kappa-FITC
      or lambda-FITC and reacquired (second acquisition). Analysis of the data was
      performed by gating on the differing intensities of CD38 and evaluating them for
      the presence of a shifting FITC-positive population from the first acquisition to
      the second acquisition. The FITC fluorescence intensity of the second acquisition
      was equal to the sum of surface CD45 expression obtained during the first
      acquisition and the cytoplasmic LC expression obtained during the second
      acquisition. Thus, the shifting (increase) of FITC fluorescence intensity during
      the second acquisition is specifically due to the cytoplasmic expression of
      either the kappa or lambda LC. We studied 15 multiple myeloma (MM) patients and
      10 controls (samples from patients without plasma cell dyscrasias). None of the
      controls showed evidence of any clonal populations. Thirteen of 15 MM patients
      exhibited clonal plasma cells (CD38 bright), ranging from 0.01% to 34% of total
      events collected. In addition, we identified another minute clonal population of
      lymphocytes (CD38 dim, CD45 bright, low forward and side scatter) in 12 of 13 MM
      patients with clonal plasma cells. This population, ranging from 0.01% to 0.6% of
      total events collected, had the same LC restriction as the clonal plasma cells.
      Patients with a ratio of minor clonal population to clonal plasma cells less than
      0.07 tended to remain in partial or complete remission than those with a ratio >
      or =0.07 (4/5 versus 1/4, P <.1, chi(2)). We conclude that this method is highly
      sensitive and permits us to identify the minute clonal population of lymphocytes
      in MM patients. Our preliminary observations with a small cohort of patients
      imply that this minute clonal population may have important prognostic
      significance. The prognostic significance should be confirmed by further studies.

PMID- 11598173
TI  - p27(Kip1) immunostaining for the differential diagnosis of small b-cell neoplasms
      in trephine bone marrow biopsies.
AB  - The distinction between mantle cell lymphoma (MCL) and other small B-cell non
      Hodgkin lymphomas (NHL) is important because MCL has a more aggressive clinical
      course. In bone marrow (BM) biopsy specimens, this distinction can be
      particularly difficult. Although cyclin D1 immunostaining and molecular detection
      of the t(11;14) translocation are highly specific markers for MCL, they fail to
      detect a proportion of cases. We have recently described that MCL typically lacks
      detectable expression of the cyclin-dependent kinase inhibitor p27(kip1) protein
      by immunostaining, which is expressed at high levels in most small B-cell NHL
      inversely correlated to the proliferation rate. We therefore examined whether
      p27(kip1) immunostaining could be a useful adjunct for the differential diagnosis
      of small B-cell NHL infiltrates in the BM. Trephine BM biopsy specimens of 96
      patients, including well-characterized MCL (19 cases), B-cell chronic lymphocytic
      leukemia (27 cases), follicular lymphoma (18 cases), hairy cell leukemia (22
      cases), and marginal zone lymphoma (10 cases) as well as 10 reactive BM,
      including five with benign lymphoid aggregates were investigated. In addition,
      the presence of a t(11;14) translocation involving the major translocation
      cluster was studied by PCR in all MCL. All cases of B-cell chronic lymphocytic
      leukemia, follicular lymphoma, and marginal zone lymphoma revealed a strong
      p27(kip1) nuclear staining in the majority of neoplastic cells. Fourteen (78%)
      cases of MCL were p27(kip1)-negative in the tumor cells, whereas four cases
      revealed a weak nuclear positivity. Seventeen (77%) cases of hairy cell leukemia
      were also either completely negative for p27(kip1) or showed a faint positive
      staining in a minority of the neoplastic cells. Nine of 19 cases (47%) of MCL
      showed a bcl1 rearrangement involving the major translocation cluster region.
      These findings demonstrate that p27(kip1) immunostaining is a valuable additional
      marker for the differential diagnosis of small B-cell NHL infiltrates in BM
      biopsies. The reduction or lack of p27(kip1) protein expression in MCL, as well
      as in hairy cell leukemia, might be an important event in the pathogenesis of
      these disorders.

PMID- 11598174
TI  - Amplification of c-myc by fluorescence in situ hybridization in a population
      based breast cancer tissue array.
AB  - A total of 261 primary breast carcinomas were analyzed for amplification of the c
      myc oncogene by fluorescence in situ hybridization performed on tumor tissue
      array samples. Results were compared with individual clinicopathologic and follow
      up data. Thirty-eight (14.6%) of the tumors showed c-myc gene amplification
      (defined as two or more additional copies of c-myc gene in relation to the number
      of chromosome 8 centromere). The reproducibility of fluorescence in situ
      hybridization assay (defined by hybridization with two different myc probes) was
      good (kappa coefficient 0.402). Statistically significant associations were found
      between c-myc amplification and DNA aneuploidy (P =.0011), and progesterone
      receptor negativity (P =.0071), and c-myc amplification also tended to be
      associated with high histologic grade (P =.064), positive axillary nodal status
      (P =.080), and a high S-phase fraction (P =.052). c-myc amplification was not
      significantly associated with overall survival of patients with invasive cancer
      (P =.32). These data from a population-based tumor material suggest that c-myc
      amplification is a feature of aggressive breast cancers, but that it is unlikely
      to be a clinically useful prognostic factor.

PMID- 11598175
TI  - Immunohistochemical expression of cell cycle proteins E2F-1, Cdk-2, Cyclin E,
      p27(kip1), and Ki-67 in normal placenta and gestational trophoblastic disease.
AB  - The role of cell cycle protein expression in gestational trophoblastic disease is
      poorly understood. In this study we investigated the immunostaining patterns of
      G(1) restriction point and G(1)-S regulatory proteins E2F-1, Cdk2, cyclin E,
      p27(kip1), and the proliferation marker Ki-67 on routinely processed sections of
      29 hydatidiform moles (10 partial moles and 19 complete moles, including 9
      persistent moles), 7 choriocarcinomas, and 7 normal placentas. Ki-67 trophoblast
      staining decreased with increasing gestational age of the placenta, and showed
      maximal expression in gestational trophoblastic disease. Cyclin-dependent kinase
      activity, as reflected by Cdk2 expression patterns, also decreased with placental
      maturation. E2F-1 was uniquely expressed by trophoblasts of moles and
      choriocarcinoma. Cyclin E was maximally expressed by complete moles and
      choriocarcinomas, and showed an inverse relationship with the cyclin-dependent
      kinase inhibitor p27(kip1). Abnormal trophoblastic proliferations may be mediated
      through interactions of Cdk-2, E2F-1, cyclin E, and p27(kip1). Overexpression of
      cyclin E was associated with more aggressive forms of gestational trophoblastic
      disease. However, we did not find distinguishing features between complete moles
      that spontaneously resolved after evacuation and persistent moles that required
      chemotherapy. The different expression patterns of cyclin E and E2F-1 in partial
      and complete moles may be useful in distinguishing these two entities.
      Furthermore, loss of p27(kip1) in malignant trophoblast may represent a necessary
      step in the development of choriocarcinoma.

PMID- 11598177
TI  - Syndecan-1 (CD138) immunoreactivity in bone marrow biopsies of multiple myeloma:
      shed syndecan-1 accumulates in fibrotic regions.
AB  - Syndecan-1 (CD138) mediates myeloma cell adhesion, and loss of syndecan-1 from
      the cell surface may contribute to myeloma proliferation and dissemination. Flow
      cytometry analysis of myeloma cells in bone marrow specimens shows heterogeneity
      in cell surface syndecan-1 expression. It is not known whether weaker expression
      correlates with more aggressive disease. However, recent reports suggest that
      variations in syndecan-1 staining intensity on myeloma cells may be an artifact
      of specimen handling. In this study, we evaluate syndecan-1 expression in bone
      marrow biopsy sections from 28 multiple myeloma patients, to elucidate the
      heterogeneity of syndecan-1 expression in situ. Immunoreactivity for syndecan-1,
      using the antibody B-B4 (CD138), was found in more than 95% of multiple myeloma
      cells in 27 of 28 biopsies. However, one biopsy had more than 50% CD138-negative
      cells and cells with weak CD138 expression were identified in the majority of
      cases. Loss of syndecan-1 did not appear to relate to myeloma cell
      differentiation. In addition, syndecan-1 was detected on intravascular and
      intrasinusoidal myeloma cells suggesting that loss of syndecan-1 may not be
      required for extramedullary dissemination. Bone marrow biopsies from nine
      additional patients, with variable CD138 staining intensity on myeloma cells as
      determined by flow cytometry, were studied by immunohistochemistry. The
      heterogeneous CD138 expression was confirmed in situ, with weakly positive cells
      concentrated in areas of reticulin fibrosis. These cells had a disrupted pattern
      of membrane staining in contrast to the strong linear membrane staining seen in
      the other multiple myeloma cells. In addition, the fibrotic stroma stained
      intensely for syndecan-1. Accumulation of syndecan-1 within the extracellular
      matrix of the marrow likely is derived by shedding of the molecule from the
      surface of myeloma cells. Because syndecan-1 can act to regulate the activity of
      heparan-binding growth factors, these reservoirs of syndecan-1 may play a
      critical role in promoting myeloma pathogenesis, or in regeneration of the tumor
      after chemotherapy.

PMID- 11598176
TI  - Inflammatory pseudotumor and sarcoma of urinary bladder: differential diagnosis
      and outcome in thirty-eight spindle cell neoplasms.
AB  - We assessed diagnostic criteria among 38 spindle cell tumors of the urinary
      bladder and obtained follow-up in 36 patients. Patients comprised 28 males and 10
      females aged 2.5 months to 87 years. Hematuria was the commonest presenting
      symptom (27 patients). After review and immunohistochemical workup, 17 patients
      had inflammatory pseudotumor (myofibroblastic tumor), 4 postoperative spindle
      cell nodule, 1 leiomyoma, 13 sarcoma (7 low-grade; 6 high-grade), and 3
      carcinoma. Mean age was 38 years for pseudotumor (range 15 to 74), 65 for
      postoperative spindle cell nodule, 51 for sarcoma, and 76 for carcinoma. Size of
      pseudotumor averaged 4.4 +/- 0.7 cm (range 1.5 to 13.0), similar to sarcoma, 4.0
      +/- 0.6 cm (range 0.5 to 7.0). Similar proportions of benign tumors and sarcomas
      had muscularis propria invasion. The criteria that best differentiated sarcoma
      from inflammatory pseudotumor were presence of necrosis at the tumor-detrusor
      muscle interface in muscle-invasive cases, and nuclear atypia. Sarcoma also had
      less prominent microvasculature, less variable cellularity, consistently > or =1
      mitotic figure per 10 high-power fields, and predominant acute inflammation
      without plasma cells. p53 protein nuclear immunostaining was moderate, unlike the
      rare to absent staining in pseudotumors. Because all 12 sarcomas were desmin
      negative, we did not call them leiomyosarcoma; they overlapped with benign tumor
      in epithelial, mesenchymal, and actin immunostaining. Among 12 sarcoma patients,
      2 died of tumor (at 3 months). Two of four experienced tumor recurrence after
      partial cystectomy (2 and 26 months). No pseudotumors recurred after
      transurethral resection or partial cystectomy, although one patient, 5 months
      after transurethral resection, had histologically identical pseudotumor that the
      surgeon considered residual. Another patient with pseudotumor, not a candidate
      for tumor ablation after transurethral resection, had continued tumor growth and
      he died of urosepsis. In conclusion, inflammatory pseudotumor, although
      overlapping with sarcoma in presentation, age range, and size, does not
      metastasize and remains histologically distinct from low-grade sarcoma.

PMID- 11598178
TI  - Reticulum cell sarcoma of lymph node with mixed dendritic and fibroblastic
      features.
AB  - We report a case of clinically aggressive reticulum cell sarcoma with mixed
      follicular dendritic cell (FDC) and fibroblastic reticular cell (FRC) features.
      Histologically, the tumor was confined to lymph nodes occurring as a multifocal
      epithelioid and spindle cell proliferation with appreciable mitotic rate and
      numerous admixed non-neoplastic B-cells. Ultrastructural examination revealed
      elongated cells with prominent nucleoli, interdigitating cell processes and
      frequent desmosomes. These features are typical of FDC sarcoma. However,
      immunohistochemical stains showed no expression of antigens characteristic of
      FDCs, including CD21, CD23 and CD35. Cytogenetic characterization of this tumor,
      by conventional G-banding and multicolor spectral karyotyping, revealed multiple
      clonal chromosomal aberrations, including del(X)(p11.4) and add (21)(p11.2). Gene
      expression analysis by cDNA microarray of RNA obtained from short-term tumor
      cultures revealed high-level expression of a set of genes (including PDGF
      receptor-alpha and -beta, certain metalloproteinases, and CD105) that were also
      highly expressed in cultures of nodal FRC cultured from non-neoplastic lymph
      nodes. We propose that this tumor represents a nodal sarcoma with intermediate
      differentiation between FDCs and FRCs. This case adds to the diversity of tumors
      that may arise from lymph node stroma and supports a possible relationship
      between the FDC and FRC lineages.

PMID- 11598179
TI  - Correspondence re: Parham DM. Pathologic classification of rhabdomyosarcomas and
      correlations with molecular studies. Mod Pathol 2001;14:506-14.

PMID- 11598181
TI  - Cytoplasmic dynein light intermediate chain is required for discrete aspects of
      mitosis in Caenorhabditis elegans.
AB  - We describe phenotypic characterization of dli-1, the Caenorhabditis elegans
      homolog of cytoplasmic dynein light intermediate chain (LIC), a subunit of the
      cytoplasmic dynein motor complex. Animals homozygous for loss-of-function
      mutations in dli-1 exhibit stochastic failed divisions in late larval cell
      lineages, resulting in zygotic sterility. dli-1 is required for dynein function
      during mitosis. Depletion of the dli-1 gene product through RNA-mediated gene
      interference (RNAi) reveals an early embryonic requirement. One-cell dli-1(RNAi)
      embryos exhibit failed cell division attempts, resulting from a variety of
      mitotic defects. Specifically, pronuclear migration, centrosome separation, and
      centrosome association with the male pronuclear envelope are defective in dli
      1(RNAi) embryos. Meiotic spindle formation, however, is not affected in these
      embryos. DLI-1, like its vertebrate homologs, contains a putative nucleotide
      binding domain similar to those found in the ATP-binding cassette transporter
      family of ATPases as well as other nucleotide-binding and -hydrolyzing proteins.
      Amino acid substitutions in a conserved lysine residue, known to be required for
      nucleotide binding, confers complete rescue in a dli-1 mutant background,
      indicating this is not an essential domain for DLI-1 function.

PMID- 11598180
TI  - Adaptins: the final recount.
AB  - Adaptins are subunits of adaptor protein (AP) complexes involved in the formation
      of intracellular transport vesicles and in the selection of cargo for
      incorporation into the vesicles. In this article, we report the results of a
      survey for adaptins from sequenced genomes including those of man, mouse, the
      fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, the plant
      Arabidopsis thaliana, and the yeasts, Saccharomyces cerevisiae and
      Schizosaccharomyces pombe. We find that humans, mice, and Arabidopsis thaliana
      have four AP complexes (AP-1, AP-2, AP-3, and AP-4), whereas D. melanogaster, C.
      elegans, S. cerevisiae, and S. pombe have only three (AP-1, AP-2, and AP-3).
      Additional diversification of AP complexes arises from the existence of adaptin
      isoforms encoded by distinct genes or resulting from alternative splicing of
      mRNAs. We complete the assignment of adaptins to AP complexes and provide
      information on the chromosomal localization, exon-intron structure, and
      pseudogenes for the different adaptins. In addition, we discuss the structural
      and evolutionary relationships of the adaptins and the genetic analyses of their
      function. Finally, we extend our survey to adaptin-related proteins such as the
      GGAs and stonins, which contain domains homologous to the adaptins.

PMID- 11598182
TI  - Activation of matrix-metalloproteinase-2 and membrane-type-1-matrix
      metalloproteinase in endothelial cells and induction of vascular permeability in
      vivo by human immunodeficiency virus-1 Tat protein and basic fibroblast growth
      factor.
AB  - Previous studies indicated that the Tat protein of human immunodeficiency virus
      type-1 (HIV-1) is a progression factor for Kaposi's sarcoma (KS). Specifically,
      extracellular Tat cooperates with basic fibroblast growth factor (bFGF) in
      promoting KS and endothelial cell growth and locomotion and in inducing KS-like
      lesions in vivo. Here we show that Tat and bFGF combined increase matrix
      metalloproteinase-2 (MMP-2) secretion and activation in endothelial cells in an
      additive/synergistic manner. These effects are due to the activation of the
      membrane-type-1-matrix-metalloproteinase and to the induction of the membrane
      bound tissue inhibitor of metalloproteinase-2 (TIMP-2) by Tat and bFGF combined,
      but also to Tat-mediated inhibition of both basal or bFGF-induced TIMP-1 and -2
      secretion. Consistent with this, Tat and bFGF promote vascular permeability and
      edema in vivo that are blocked by a synthetic MMP inhibitor. Finally, high MMP-2
      expression is detected in acquired immunodeficiency virus syndrome (AIDS)-KS
      lesions, and increased levels of MMP-2 are found in plasma from patients with
      AIDS-KS compared with HIV-uninfected individuals with classic KS, indicating that
      these mechanisms are operative in AIDS-KS. This suggests a novel pathway by which
      Tat can increase KS aggressiveness or induce vasculopathy in the setting of HIV-1
      infection.

PMID- 11598183
TI  - Lipid rafts act as specialized domains for tetanus toxin binding and
      internalization into neurons.
AB  - Tetanus (TeNT) is a zinc protease that blocks neurotransmission by cleaving the
      synaptic protein vesicle-associated membrane protein/synaptobrevin. Although its
      intracellular catalytic activity is well established, the mechanism by which this
      neurotoxin interacts with the neuronal surface is not known. In this study, we
      characterize p15s, the first plasma membrane TeNT binding proteins and we show
      that they are glycosylphosphatidylinositol-anchored glycoproteins in nerve growth
      factor (NGF)-differentiated PC12 cells, spinal cord cells, and purified motor
      neurons. We identify p15 as neuronal Thy-1 in NGF-differentiated PC12 cells.
      Fluorescence lifetime imaging microscopy measurements confirm the close
      association of the binding domain of TeNT and Thy-1 at the plasma membrane. We
      find that TeNT is recruited to detergent-insoluble lipid microdomains on the
      surface of neuronal cells. Finally, we show that cholesterol depletion affects a
      raft subpool and blocks the internalization and intracellular activity of the
      toxin. Our results indicate that TeNT interacts with target cells by binding to
      lipid rafts and that cholesterol is required for TeNT internalization and/or
      trafficking in neurons.

PMID- 11598184
TI  - Regulation of the mitotic exit protein kinases Cdc15 and Dbf2.
AB  - In budding yeast, the release of the protein phosphatase Cdc14 from its inhibitor
      Cfi1/Net1 in the nucleolus during anaphase triggers the inactivation of Clb CDKs
      that leads to exit from mitosis. The mitotic exit pathway controls the
      association between Cdc14 and Cfi1/Net1. It is comprised of the RAS-like GTP
      binding protein Tem1, the exchange factor Lte1, the GTPase activating protein
      complex Bub2-Bfa1/Byr4, and several protein kinases including Cdc15 and Dbf2.
      Here we investigate the regulation of the protein kinases Dbf2 and Cdc15. We find
      that Cdc15 is recruited to both spindle pole bodies (SPBs) during anaphase. This
      recruitment depends on TEM1 but not DBF2 or CDC14 and is inhibited by BUB2. Dbf2
      also localizes to SPBs during anaphase, which coincides with activation of Dbf2
      kinase activity. Both events depend on the mitotic exit pathway components TEM1
      and CDC15. In cells lacking BUB2, Dbf2 localized to SPBs in cell cycle stages
      other than anaphase and telophase and Dbf2 kinase was prematurely active during
      metaphase. Our results suggest an order of function of mitotic exit pathway
      components with respect to SPB localization of Cdc15 and Dbf2 and activation of
      Dbf2 kinase. BUB2 negatively regulates all 3 events. Loading of Cdc15 on SPBs
      depends on TEM1, whereas loading of Dbf2 on SPBs and activation of Dbf2 kinase
      depend on TEM1 and CDC15.

PMID- 11598185
TI  - Urokinase receptors promote beta1 integrin function through interactions with
      integrin alpha3beta1.
AB  - The urokinase receptor (uPAR) is linked to cellular migration through its
      capacity to promote pericellular proteolysis, regulate integrin function, and
      mediate cell signaling in response to urokinase (uPA) binding. The mechanisms for
      these activities remain incompletely defined, although uPAR was recently
      identified as a cis-acting ligand for the beta2 integrin CD11b/CD18 (Mac-1). Here
      we show that a major beta1 integrin partner for uPAR/uPA signaling is alpha3. In
      uPAR-transfected 293 cells uPAR complexed (>90%) with alpha3beta1 and antibodies
      to alpha3 blocked uPAR-dependent vitronectin (Vn) adhesion. Soluble uPAR bound to
      recombinant alpha3beta1 in a uPA-dependent manner (K(d) < 20 nM) and binding was
      blocked by a 17-mer alpha3beta1 integrin peptide (alpha325) homologous to the
      CD11b uPAR-binding site. uPAR colocalized with alpha3beta1 in MDA-MB-231 cells
      and uPA (1 nM) enhanced spreading and focal adhesion kinase phosphorylation on
      fibronectin (Fn) or collagen type I (Col) in a pertussis toxin- and alpha325
      sensitive manner. A critical role of alpha3beta1 in uPA signaling was verified by
      studies of epithelial cells from alpha3-deficient mice. Thus, uPAR preferentially
      complexes with alpha3beta1, promoting direct (Vn) and indirect (Fn, Col) pathways
      of cell adhesion, the latter a heterotrimeric G protein-dependent mechanism of
      signaling between alpha3beta1 and other beta1 integrins.

PMID- 11598186
TI  - Genomic expression responses to DNA-damaging agents and the regulatory role of
      the yeast ATR homolog Mec1p.
AB  - Eukaryotic cells respond to DNA damage by arresting the cell cycle and modulating
      gene expression to ensure efficient DNA repair. The human ATR kinase and its
      homolog in yeast, MEC1, play central roles in transducing the damage signal. To
      characterize the role of the Mec1 pathway in modulating the cellular response to
      DNA damage, we used DNA microarrays to observe genomic expression in
      Saccharomyces cerevisiae responding to two different DNA-damaging agents. We
      compared the genome-wide expression patterns of wild-type cells and mutants
      defective in Mec1 signaling, including mec1, dun1, and crt1 mutants, under normal
      growth conditions and in response to the methylating-agent methylmethane
      sulfonate (MMS) and ionizing radiation. Here, we present a comparative analysis
      of wild-type and mutant cells responding to these DNA-damaging agents, and
      identify specific features of the gene expression responses that are dependent on
      the Mec1 pathway. Among the hundreds of genes whose expression was affected by
      Mec1p, one set of genes appears to represent an MEC1-dependent expression
      signature of DNA damage. Other aspects of the genomic responses were independent
      of Mec1p, and likely independent of DNA damage, suggesting the pleiotropic
      effects of MMS and ionizing radiation. The complete data set as well as
      supplemental materials is available at http://www-genome.stanford.edu/mec1.

PMID- 11598187
TI  - Characterization of a di-leucine-based signal in the cytoplasmic tail of the
      nucleotide-pyrophosphatase NPP1 that mediates basolateral targeting but not
      endocytosis.
AB  - Enzymes of the nucleotide pyrophosphatase/phosphodiesterase (NPPase) family are
      expressed at opposite surfaces in polarized epithelial cells. We investigated the
      targeting signal of NPP1, which is exclusively expressed at the basolateral
      surface. Full-length NPP1 and different constructs and mutants were transfected
      into the polarized MDCK cell line. Expression of the proteins was analyzed by
      confocal microscopy and surface biotinylation. The basolateral signal of NPP1 was
      identified as a di-leucine motif located in the cytoplasmic tail. Mutation of
      either or both leucines largely redirected NPP1 to the apical surface.
      Furthermore, addition of the conserved sequence AAASLLAP redirected the apical
      nucleotide pyrophosphatase/phosphodiesterase NPP3 to the basolateral surface.
      Full-length NPP1 was not significantly internalized. However, when the
      cytoplasmic tail was deleted upstream the di-leucine motif or when the six
      upstream flanking amino acids were deleted, the protein was mainly found
      intracellularly. Endocytosis experiments indicated that these mutants were
      endocytosed from the basolateral surface. These results identify the basolateral
      signal of NPP1 as a short sequence including a di-leucine motif that is dominant
      over apical determinants and point to the importance of surrounding amino acids
      in determining whether the signal will function as a basolateral signal only or
      as an endocytotic signal as well.

PMID- 11598188
TI  - On the evolutionary conservation of the cell death pathway: mitochondrial release
      of an apoptosis-inducing factor during Dictyostelium discoideum cell death.
AB  - Mitochondria play a pivotal role in apoptosis in multicellular organisms by
      releasing apoptogenic factors such as cytochrome c that activate the caspases
      effector pathway, and apoptosis-inducing factor (AIF) that is involved in a
      caspase-independent cell death pathway. Here we report that cell death in the
      single-celled organism Dictyostelium discoideum involves early disruption of
      mitochondrial transmembrane potential (DeltaPsim) that precedes the induction of
      several apoptosis-like features, including exposure of the phosphatidyl residues
      at the external surface of the plasma membrane, an intense vacuolization, a
      fragmentation of DNA into large fragments, an autophagy, and the release of
      apoptotic corpses that are engulfed by neighboring cells. We have cloned a
      Dictyostelium homolog of mammalian AIF that is localized into mitochondria and is
      translocated from the mitochondria to the cytoplasm and the nucleus after the
      onset of cell death. Cytoplasmic extracts from dying Dictyostelium cells trigger
      the breakdown of isolated mammalian and Dictyostelium nuclei in a cell-free
      system, and this process is inhibited by a polyclonal antibody specific for
      Dictyostelium discoideum apoptosis-inducing factor (DdAIF), suggesting that DdAIF
      is involved in DNA degradation during Dictyostelium cell death. Our findings
      indicate that the cell death pathway in Dictyostelium involves mitochondria and
      an AIF homolog, suggesting the evolutionary conservation of at least part of the
      cell death pathway in unicellular and multicellular organisms.

PMID- 11598189
TI  - Glycosylphosphatidyl inositol-anchored proteins and fyn kinase assemble in
      noncaveolar plasma membrane microdomains defined by reggie-1 and -2.
AB  - Using confocal laser scanning and double immunogold electron microscopy, we
      demonstrate that reggie-1 and -2 are colocalized in < or =0.1-microm plasma
      membrane microdomains of neurons and astrocytes. In astrocytes, reggie-1 and -2
      do not occur in caveolae but clearly outside these structures. Microscopy and
      coimmunoprecipitation show that reggie-1 and -2 are associated with fyn kinase
      and with the glycosylphosphatidyl inositol-anchored proteins Thy-1 and F3 that,
      when activated by antibody cross-linking, selectively copatch with reggie. Jurkat
      cells, after cross-linking of Thy-1 or GM1 (with the use of cholera toxin),
      exhibit substantial colocalization of reggie-1 and -2 with Thy-1, GM1, the T-cell
      receptor complex and fyn. This, and the accumulation of reggie proteins in
      detergent-resistant membrane fractions containing F3, Thy-1, and fyn imparts to
      reggie-1 and -2 properties of raft-associated proteins. It also suggests that
      reggie-1 and -2 participate in the formation of signal transduction centers. In
      addition, we find reggie-1 and -2 in endolysosomes. In Jurkat cells, reggie-1 and
      -2 together with fyn and Thy-1 increase in endolysosomes concurrent with a
      decrease at the plasma membrane. Thus, reggie-1 and -2 define raft-related
      microdomain signaling centers in neurons and T cells, and the protein complex
      involved in signaling becomes subject to degradation.

PMID- 11598190
TI  - Association of human DEAD box protein DDX1 with a cleavage stimulation factor
      involved in 3'-end processing of pre-MRNA.
AB  - DEAD box proteins are putative RNA helicases that function in all aspects of RNA
      metabolism, including translation, ribosome biogenesis, and pre-mRNA splicing.
      Because many processes involving RNA metabolism are spatially organized within
      the cell, we examined the subcellular distribution of a human DEAD box protein,
      DDX1, to identify possible biological functions. Immunofluorescence labeling of
      DDX1 demonstrated that in addition to widespread punctate nucleoplasmic labeling,
      DDX1 is found in discrete nuclear foci approximately 0.5 microm in diameter.
      Costaining with anti-Sm and anti-promyelocytic leukemia (PML) antibodies
      indicates that DDX1 foci are frequently located next to Cajal (coiled) bodies and
      less frequently, to PML bodies. Most importantly, costaining with anti-CstF-64
      antibody indicates that DDX1 foci colocalize with cleavage bodies. By microscopic
      fluorescence resonance energy transfer, we show that labeled DDX1 resides within
      a Forster distance of 10 nm of labeled CstF-64 protein in both the nucleoplasm
      and within cleavage bodies. Coimmunoprecipitation analysis indicates that a
      proportion of CstF-64 protein resides in the same complex as DDX1. These studies
      are the first to identify a DEAD box protein associating with factors involved in
      3'-end cleavage and polyadenylation of pre-mRNAs.

PMID- 11598191
TI  - Characterization of human palladin, a microfilament-associated protein.
AB  - Actin-containing microfilaments control cell shape, adhesion, and contraction. In
      striated muscle, alpha-actinin and other Z-disk proteins coordinate the
      organization and functions of actin filaments. In smooth muscle and nonmuscle
      cells, periodic structures termed dense bodies and dense regions, respectively,
      are thought to serve functions analogous to Z-discs. We describe here
      identification and characterization of human palladin, a protein expressed mainly
      in smooth muscle and nonmuscle and distributed along microfilaments in a periodic
      manner consistent with dense regions/bodies. Palladin contains three Ig-domains
      most homologous to the sarcomeric Z-disk protein myotilin. The N terminus
      includes an FPPPP motif recognized by the Ena-Vasp homology domain 1 domain in
      Ena/vasodilatator-stimulated phosphoprotein (VASP)/Wiscott-Aldrich syndrome
      protein (WASP) protein family. Cytoskeletal proteins with FPPPP motif target
      Ena/VASP/WASP proteins to sites of actin modulation. We identified palladin in a
      yeast two-hybrid search as an ezrin-associated protein. An interaction between
      palladin and ezrin was further verified by affinity precipitation and blot
      overlay assays. The interaction was mediated by the alpha-helical domain of ezrin
      and by Ig-domains 2-3 of palladin. Ezrin is typically a component of the cortical
      cytoskeleton, but in smooth muscle cells it is localized along microfilaments.
      These cells express palladin abundantly and thus palladin may be involved in the
      microfilament localization of ezrin. Palladin expression was up-regulated in
      differentiating dendritic cells (DCs), coinciding with major cytoskeletal and
      morphological alterations. In immature DCs, palladin localized in actin
      containing podosomes and in mature DCs along actin filaments. The regulated
      expression and localization suggest a role for palladin in the assembly of DC
      cytoskeleton.

PMID- 11598193
TI  - Cooperative control of Akt phosphorylation, bcl-2 expression, and apoptosis by
      cytoskeletal microfilaments and microtubules in capillary endothelial cells.
AB  - Capillary endothelial cells can be switched between growth and apoptosis by
      modulating their shape with the use of micropatterned adhesive islands. The
      present study was carried out to examine whether cytoskeletal filaments
      contribute to this response. Disruption of microfilaments or microtubules with
      the use of cytochalasin D or nocodazole, respectively, led to levels of apoptosis
      in capillary cells equivalent to that previously demonstrated by inducing cell
      rounding with the use of micropatterned culture surfaces containing small (<20
      microm in diameter) circular adhesive islands coated with fibronectin.
      Simultaneous disruption of microfilaments and microtubules led to more pronounced
      cell rounding and to enhanced levels of apoptosis approaching that observed
      during anoikis in fully detached (suspended) cells, indicating that these two
      cytoskeletal filament systems can cooperate to promote cell survival. Western
      blot analysis revealed that the protein kinase Akt, which is known to be critical
      for control of cell survival became dephosphorylated during cell rounding induced
      by disruption of the cytoskeleton, and that this was accompanied by a decrease in
      bcl-2 expression as well as a subsequent increase in caspase activation. This
      ability of the cytoskeleton to control capillary endothelial cell survival may be
      important for understanding the relationship among extracellular matrix turnover,
      cell shape changes, and apoptosis during angiogenesis inhibition.

PMID- 11598192
TI  - Dual role of H-Ras in regulation of lymphocyte function antigen-1 activity by
      stromal cell-derived factor-1alpha: implications for leukocyte transmigration.
AB  - We investigated the role of H-Ras in chemokine-induced integrin regulation in
      leukocytes. Stimulation of Jurkat T cells with the CXC chemokine stromal cell
      derived factor-1alpha (SDF-1alpha) resulted in a rapid increase in the
      phosphorylation, i.e., activation of extracellular signal receptor-activated
      kinase (ERK) but not c-Jun NH(2)-terminal kinase or p38 kinase, and
      phosphorylation of Akt, reflecting phosphatidylinositol 3-kinase (PI3-K)
      activation. Phosphorylation of ERK in Jurkat cells was enhanced and attenuated by
      expression of dominant active (D12) or inactive (N17) forms of H-Ras,
      respectively, while N17 H-Ras abrogated SDF-1alpha-induced Akt phosphorylation.
      SDF-1alpha triggered a transient regulation of adhesion to intercellular adhesion
      molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 mediated by lymphocyte
      function antigen-1 (LFA-1) and very late antigen-4 (VLA-4), respectively, and a
      rapid increase in LFA-1 binding to soluble ICAM-1.Ig, which was inhibited by D12
      but not N17 H-Ras. Both D12 and N17 H-Ras abrogated the regulation of LFA-1 but
      not VLA-4 avidity, and impaired LFA-1-mediated transendothelial chemotaxis but
      not VLA-4-dependent transmigration induced by SDF-1alpha. Analysis of the mutant
      Jurkat J19 clone revealed LFA-1 with constitutively high affinity and reduced ERK
      phosphorylation, which were partially restored by expression of active H-Ras.
      Inhibition of PI3-K blocked the up-regulation of Jurkat cell adhesion to ICAM-1
      by SDF-1alpha, whereas inhibition of mitogen-activated protein kinase kinase
      impaired the subsequent down-regulation and blocking both pathways abrogated LFA
      1 regulation. Our data suggest that inhibition of initial PI3-K activation by
      inactive H-Ras or sustained activation of an inhibitory ERK pathway by active H
      Ras prevail to abolish LFA-1 regulation and transendothelial migration induced by
      SDF-1alpha in leukocytes, establishing a complex and bimodal involvement of H
      Ras.

PMID- 11598194
TI  - Rab3a is involved in transport of synaptic vesicles to the active zone in mouse
      brain nerve terminals.
AB  - The rab family of GTP-binding proteins regulates membrane transport between
      intracellular compartments. The major rab protein in brain, rab3A, associates
      with synaptic vesicles. However, rab3A was shown to regulate the fusion
      probability of synaptic vesicles, rather than their transport and docking. We
      tested whether rab3A has a transport function by analyzing synaptic vesicle
      distribution and exocytosis in rab3A null-mutant mice. Rab3A deletion did not
      affect the number of vesicles and their distribution in resting nerve terminals.
      The secretion response upon a single depolarization was also unaffected. In
      normal mice, a depolarization pulse in the presence of Ca(2+) induces an
      accumulation of vesicles close to and docked at the active zone (recruitment).
      Rab3A deletion completely abolished this activity-dependent recruitment, without
      affecting the total number of vesicles. Concomitantly, the secretion response in
      the rab3A-deficient terminals recovered slowly and incompletely after exhaustive
      stimulation, and the replenishment of docked vesicles after exhaustive
      stimulation was also impaired in the absence of rab3A. These data indicate that
      rab3A has a function upstream of vesicle fusion in the activity-dependent
      transport of synaptic vesicles to and their docking at the active zone.

PMID- 11598195
TI  - Zyxin is not colocalized with vasodilator-stimulated phosphoprotein (VASP) at
      lamellipodial tips and exhibits different dynamics to vinculin, paxillin, and
      VASP in focal adhesions.
AB  - Actin polymerization is accompanied by the formation of protein complexes that
      link extracellular signals to sites of actin assembly such as membrane ruffles
      and focal adhesions. One candidate recently implicated in these processes is the
      LIM domain protein zyxin, which can bind both Ena/vasodilator-stimulated
      phosphoprotein (VASP) proteins and the actin filament cross-linking protein alpha
      actinin. To characterize the localization and dynamics of zyxin in detail, we
      generated both monoclonal antibodies and a green fluorescent protein (GFP)-fusion
      construct. The antibodies colocalized with ectopically expressed GFP-VASP at
      focal adhesions and along stress fibers, but failed to label lamellipodial and
      filopodial tips, which also recruit Ena/VASP proteins. Likewise, neither
      microinjected, fluorescently labeled zyxin antibodies nor ectopically expressed
      GFP-zyxin were recruited to these latter sites in live cells, whereas both probes
      incorporated into focal adhesions and stress fibers. Comparing the dynamics of
      zyxin with that of the focal adhesion protein vinculin revealed that both
      proteins incorporated simultaneously into newly formed adhesions. However, during
      spontaneous or induced focal adhesion disassembly, zyxin delocalization preceded
      that of either vinculin or paxillin. Together, these data identify zyxin as an
      early target for signals leading to adhesion disassembly, but exclude its role in
      recruiting Ena/VASP proteins to the tips of lamellipodia and filopodia.

PMID- 11598196
TI  - Serial analysis of gene expression in Plasmodium falciparum reveals the global
      expression profile of erythrocytic stages and the presence of anti-sense
      transcripts in the malarial parasite.
AB  - Serial analysis of gene expression (SAGE) was applied to the malarial parasite
      Plasmodium falciparum to characterize the comprehensive transcriptional profile
      of erythrocytic stages. A SAGE library of approximately 8335 tags representing
      4866 different genes was generated from 3D7 strain parasites. Basic local
      alignment search tool analysis of high abundance SAGE tags revealed that a
      majority (88%) corresponded to 3D7 sequence, and despite the low complexity of
      the genome, 70% of these highly abundant tags matched unique loci.
      Characterization of these suggested the major metabolic pathways that are used by
      the organism under normal culture conditions. Furthermore several tags expressed
      at high abundance (30% of tags matching to unique loci of the 3D7 genome) were
      derived from previously uncharacterized open reading frames, demonstrating the
      use of SAGE in genome annotation. The open platform "profiling" nature of SAGE
      also lead to the important discovery of a novel transcriptional phenomenon in the
      malarial pathogen: a significant number of highly abundant tags that were derived
      from annotated genes (17%) corresponded to antisense transcripts. These SAGE data
      were validated by two independent means, strand specific reverse transcription
      polymerase chain reaction and Northern analysis, where antisense messages were
      detected in both asexual and sexual stages. This finding has implications for
      transcriptional regulation of Plasmodium gene expression.

PMID- 11598197
TI  - Cross talk between beta(1) and alpha(V) integrins: beta(1) affects beta(3) mRNA
      stability.
AB  - There is increasing evidence that a fine-tuned integrin cross talk can generate a
      high degree of specificity in cell adhesion, suggesting that spatially and
      temporally coordinated expression and activation of integrins are more important
      for regulated cell adhesive functions than the intrinsic specificity of
      individual receptors. However, little is known concerning the molecular
      mechanisms of integrin cross talk. With the use of beta(1)-null GD25 cells
      ectopically expressing the beta(1)A integrin subunit, we provide evidence for the
      existence of a cross talk between beta(1) and alpha(V) integrins that affects the
      ratio of alpha(V)beta(3) and alpha(V)beta(5) integrin cell surface levels. In
      particular, we demonstrate that a down-regulation of alpha(V)beta(3) and an up
      regulation of alpha(V)beta(5) occur as a consequence of beta(1)A expression.
      Moreover, with the use of GD25 cells expressing the integrin isoforms beta(1)B
      and beta(1)D, as well as two beta(1) cytoplasmic domain deletion mutants lacking
      either the entire cytoplasmic domain (beta(1)TR) or only its "variable" region
      (beta(1)COM), we show that the effects of beta(1) over alpha(V) integrins take
      place irrespective of the type of beta(1) isoform, but require the presence of
      the "common" region of the beta(1) cytoplasmic domain. In an attempt to establish
      the regulatory mechanism(s) whereby beta(1) integrins exert their trans-acting
      functions, we have found that the down-regulation of alpha(V)beta(3) is due to a
      decreased beta(3) subunit mRNA stability, whereas the up-regulation of
      alpha(V)beta(5) is mainly due to translational or posttranslational events. These
      findings provide the first evidence for an integrin cross talk based on the
      regulation of mRNA stability.

PMID- 11598198
TI  - p38-mediated regulation of an Fas-associated death domain protein-independent
      pathway leading to caspase-8 activation during TGFbeta-induced apoptosis in human
      Burkitt lymphoma B cells BL41.
AB  - On binding to its receptor, transforming growth factor beta (TGFbeta) induces
      apoptosis in a variety of cells, including human B lymphocytes. We have
      previously reported that TGFbeta-mediated apoptosis is caspase-dependent and
      associated with activation of caspase-3. We show here that caspase-8 inhibitors
      strongly decrease TGFbeta-mediated apoptosis in BL41 Burkitt's lymphoma cells.
      These inhibitors act upstream of the mitochondria because they inhibited the loss
      of mitochondrial membrane potential observed in TGFbeta-treated cells. TGFbeta
      induced caspase-8 activation in these cells as shown by the cleavage of specific
      substrates, including Bid, and the appearance of cleaved fragments of caspase-8.
      Our data show that TGFbeta induces an apoptotic pathway involving sequential
      caspase-8 activation, loss of mitochondrial membrane potential, and caspase-9 and
      -3 activation. Caspase-8 activation was Fas-associated death domain protein
      (FADD)-independent because cells expressing a dominant negative mutant of FADD
      were still sensitive to TGFbeta-induced caspase-8 activation and apoptosis. This
      FADD-independent pathway of caspase-8 activation is regulated by p38. Indeed,
      TGFbeta-induced activation of p38 and two different inhibitors specific for this
      mitogen-activated protein kinase pathway (SB203580 and PD169316) prevented
      TGFbeta-mediated caspase-8 activation as well as the loss of mitochondrial
      membrane potential and apoptosis. Overall, our data show that p38 activation by
      TGFbeta induced an apoptotic pathway via FADD-independent activation of caspase
      8.

PMID- 11598199
TI  - Lumenal endosomal and Golgi-retrieval determinants involved in pH-sensitive
      targeting of an early Golgi protein.
AB  - Despite the potential importance of retrieval-based targeting, few Golgi
      cisternae-localized proteins have been demonstrated to be targeted by retrieval,
      and the putative retrieval signals remain unknown. Golgi phosphoprotein of 130
      kDa (GPP130) is a cis-Golgi protein that allows assay of retrieval-based
      targeting because it redistributes to endosomes upon treatment with agents that
      disrupt lumenal pH, and it undergoes endosome-to-Golgi retrieval upon drug
      removal. Analysis of chimeric molecules containing domains from GPP130 and the
      plasma membrane protein dipeptidylpeptidase IV indicated that GPP130 targeting
      information is contained entirely within its lumenal domain. Dissection of the
      lumenal domain indicated that a predicted coiled-coil stem domain adjacent to the
      transmembrane domain was both required and sufficient for pH-sensitive Golgi
      localization and endosome-to-Golgi retrieval. Further dissection of this stem
      domain revealed two noncontiguous stretches that each conferred Golgi
      localization separated by a stretch that conferred endosomal targeting.
      Importantly, in the absence of the endosomal determinant the Golgi targeting of
      constructs containing either or both of the Golgi determinants became insensitive
      to pH disruption by monensin. Because monensin blocks endosome-to-Golgi
      transport, the finding that the endosomal determinant confers monensin
      sensitivity suggests that the endosomal determinant causes GPP130 to traffic to
      endosomes from which it is normally retrieved. Thus, our observations identify
      Golgi and endosomal targeting determinants within a lumenal predicted coiled-coil
      domain that appear to act coordinately to mediate retrieval-based targeting of
      GPP130.

PMID- 11598200
TI  - Gamma-tubulin and the C-terminal motor domain kinesin-like protein, KLPA,
      function in the establishment of spindle bipolarity in Aspergillus nidulans.
AB  - Previous research has found that a gamma-tubulin mutation in Schizosaccharomyces
      pombe is synthetically lethal with a deletion of the C-terminal motor domain
      kinesin-like protein gene pkl1, but the lethality of the double mutant prevents a
      phenotypic analysis of the synthetic interaction. We have investigated
      interactions between klpA1, a deletion of an Aspergillus nidulans homolog of
      pkl1, and mutations in the mipA, gamma-tubulin gene. We find that klpA1
      dramatically increases the cold sensitivity and slightly reduces the growth rate
      at all temperatures, of three mipA alleles. In synchronized cells we find that
      klpA1 causes a substantial but transient inhibition of the establishment of
      spindle bipolarity. At a restrictive temperature, mipAD123 causes a slight,
      transient inhibition of spindle bipolarity and a more significant inhibition of
      anaphase A. In the mipAD123/klpA1 strain, formation of bipolar spindles is more
      strongly inhibited than in the klpA1 single mutant and many spindles apparently
      never become bipolar. These results indicate, surprisingly, that gamma-tubulin
      and the klpA kinesin have overlapping roles in the establishment of spindle
      bipolarity. We propose a model to account for these data.

PMID- 11598202
TI  - Role for telomere cap structure in meiosis.
AB  - Telomeres, the natural ends of eukaryotic chromosomes, are essential for the
      protection of chromosomes from end-to-end fusions, recombination, and shortening.
      Here we explore their role in the process of meiotic division in the budding
      yeast, Kluyveromyces lactis. Telomerase RNA mutants that cause unusually long
      telomeres with deregulated structure led to severely defective meiosis. The
      severity of the meiotic phenotype of two mutants correlated with the degree of
      loss of binding of the telomere binding protein Rap1p. We show that telomere size
      and the extent of potential Rap1p binding to the entire telomere are irrelevant
      to the process of meiosis. Moreover, we demonstrate that extreme difference in
      telomere size between two homologous chromosomes is compatible with the normal
      function of telomeres during meiosis. In contrast, the structure of the most
      terminal telomeric repeats is critical for normal meiosis. Our results
      demonstrate that telomeres play a critical role during meiotic division and that
      their terminal cap structure is essential for this role.

PMID- 11598201
TI  - A novel mechanism for localizing membrane proteins to yeast trans-Golgi network
      requires function of synaptojanin-like protein.
AB  - Localization of resident membrane proteins to the yeast trans-Golgi network (TGN)
      involves both their retrieval from a prevacuolar/endosomal compartment (PVC) and
      a "slow delivery" mechanism that inhibits their TGN-to-PVC transport. A screen
      for genes required for the slow delivery mechanism uncovered INP53, a gene
      encoding a phosphoinositide phosphatase. A retrieval-defective model TGN protein,
      A(F-->A)-ALP, was transported to the vacuole in inp53 mutants approximately
      threefold faster than in wild type. Inp53p appears to function in a process
      distinct from PVC retrieval because combining inp53 with mutations that block
      retrieval resulted in a much stronger phenotype than either mutation alone. In
      vps27 strains defective for both anterograde and retrograde transport out of the
      PVC, a loss of Inp53p function markedly accelerated the rate of transport of TGN
      residents A-ALP and Kex2p into the PVC. Inp53p function is cargo specific because
      a loss of Inp53p function had no effect on the rate of Vps10p transport to the
      PVC in vps27 cells. The rate of early secretory pathway transport appeared to be
      unaffected in inp53 mutants. Cell fractionation experiments suggested that Inp53p
      associates with Golgi or endosomal membranes. Taken together, these results
      suggest that a phosphoinositide signaling event regulates TGN-to-PVC transport of
      select cargo proteins.

PMID- 11598203
TI  - Ggamma in dictyostelium: its role in localization of gbetagamma to the membrane
      is required for chemotaxis in shallow gradients.
AB  - G-protein-mediated signal transduction pathways play an essential role in the
      developmental program of the simple eukaryotic organism Dictyostelium discoideum.
      Database searches have yielded 11 Galpha-subunits, a single Gbeta-subunit, but no
      Ggamma-subunits. We report here the purification, cDNA isolation, and functional
      analysis of a Ggamma-subunit. Like Gbeta, the Ggamma appears to be unique and
      hybridization studies show that Ggamma and Gbeta are expressed in parallel during
      development. Species-wide sequence comparisons of Ggamma-subunits and gamma-like
      domains of RGS proteins reveal short stretches of highly conserved residues as
      well as the common CXXL motif at the COOH-terminal of Ggammas that target
      Gbetagammas to plasma membrane. Overexpression of a CSVL-deleted Ggamma
      (GgammaDelta) in wild-type cells shifts Gbetagamma to the cytosol and selectively
      impairs certain G-protein-mediated signal transduction pathways. These cells are
      able to respond to increments in the stimulus, but are unable to sense
      chemoattractant gradients. They neither move directionally nor recruit PH-domains
      to their leading edge. Thus, a full complement of membrane-tethered Gbetagamma is
      required for sensing shallow gradients, but is not essential for responses to
      increments in extracellular stimuli.

PMID- 11598204
TI  - The cytoplasmic domain of the integrin alpha9 subunit requires the adaptor
      protein paxillin to inhibit cell spreading but promotes cell migration in a
      paxillin-independent manner.
AB  - The integrin alpha9 subunit forms a single heterodimer, alpha9beta1. The alpha9
      subunit is most closely related to the alpha4 subunit, and like alpha4 integrins,
      alpha9beta1 plays an important role in leukocyte migration. The alpha4
      cytoplasmic domain preferentially enhances cell migration and inhibits cell
      spreading, effects that depend on interaction with the adaptor protein, paxillin.
      To determine whether the alpha9 cytoplasmic domain has similar effects, a series
      of chimeric and deleted alpha9 constructs were expressed in Chinese hamster ovary
      cells and tested for their effects on migration and spreading on an alpha9beta1
      specific ligand. Like alpha4, the alpha9 cytoplasmic domain enhanced cell
      migration and inhibited cell spreading. Paxillin also specifically bound the
      alpha9 cytoplasmic domain and to a similar level as alpha4. In paxillin(-/-)
      cells, alpha9 failed to inhibit cell spreading as expected but surprisingly still
      enhanced cell migration. Further, mutations that abolished the alpha9-paxillin
      interaction prevented alpha9 from inhibiting cell spreading but had no effect on
      alpha9-dependent cell migration. These findings suggest that the mechanisms by
      which the cytoplasmic domains of integrin alpha subunits enhance migration and
      inhibit cell spreading are distinct and that the alpha9 and alpha4 cytoplasmic
      domains, despite sequence and functional similarities, enhance cell migration by
      different intracellular signaling pathways.

PMID- 11598205
TI  - The conserved npl4 protein complex mediates proteasome-dependent membrane-bound
      transcription factor activation.
AB  - Proteolytic activation of membrane-bound transcription factors has emerged as an
      important mechanism for the regulation of gene expression. Two membrane-bound
      transcription factors regulated in this manner are the Saccharomyces cerevisiae
      proteins Mga2p and Spt23p, which direct transcription of the Delta9-fatty acid
      desaturase gene OLE1. We now show that a membrane-associated complex containing
      the highly conserved Npl4p, Ufd1p, and Cdc48p proteins mediates the proteasome
      regulated cleavage of Mga2p and Spt23p. Mutations in NPL4, UFD1, and CDC48 cause
      a block in Mga2p and Spt23p processing, with concomitant loss of OLE1 expression.
      Taken together, our data indicate that the Npl4 complex may serve to target the
      proteasome to the ubiquitinated endoplasmic reticulum membrane-bound proteins
      Mga2p and Spt23p. Given the recent finding that NPL4 is allelic to the ERAD gene
      HRD4, we further propose that this NPL4 function extends to all endoplasmic
      reticulum-membrane-associated targets of the proteasome.

PMID- 11598206
TI  - Vps26p, a component of retromer, directs the interactions of Vps35p in endosome
      to-Golgi retrieval.
AB  - Endosome-to-Golgi retrieval of the carboxypeptidase Y receptor Vps10p is mediated
      by a recently discovered membrane coat complex termed retromer. Retromer
      comprises five conserved proteins: Vps35p, Vps29p, Vps5p, Vps17p, and Vps26p.
      Vps35p recognizes cargo molecules such as Vps10p and interacts strongly with
      Vps29p. Vps5p forms a subcomplex with Vps17p and has been proposed to play a
      structural role by self-assembling into large multimeric structures. The function
      of Vps26p is currently unknown. We have investigated the role that Vps26p plays
      in retromer-mediated endosome-to-Golgi transport by analyzing dominant negative
      alleles of Vps26p. These mutants have identified a crucial region of Vps26p that
      plays an important role in its function. Functional domains of Vps26p have been
      investigated by the creation of yeast-mouse hybrid molecules in which domains of
      Vps26p have been replaced by the similar domain in the protein encoded by the
      mouse VPS26 gene, Hbeta58. These domain swap experiments have shown that Vps26p
      promotes the interactions between the cargo-selective component Vps35p and the
      structural components Vps5p/Vps17p.

PMID- 11598207
TI  - Rapid intermittent movement of axonal neurofilaments observed by fluorescence
      photobleaching.
AB  - Observations on naturally occurring gaps in the axonal neurofilament array of
      cultured neurons have demonstrated that neurofilament polymers move along axons
      in a rapid, intermittent, and highly asynchronous manner. In contrast, studies on
      axonal neurofilaments using laser photobleaching have not detected movement.
      Here, we describe a modified photobleaching strategy that does permit the direct
      observation of neurofilament movement. Axons of cultured neurons expressing GFP
      tagged neurofilament protein were bleached by excitation with the mercury arc
      lamp of a conventional epifluorescence microscope for 12-60 s. The length of the
      bleached region ranged from 10 to 60 microm. By bleaching thin axons, which have
      relatively few neurofilaments, we were able to reduce the fluorescent intensity
      enough to allow the detection of neurofilaments that moved in from the
      surrounding unbleached regions. Time-lapse imaging at short intervals revealed
      rapid, intermittent, and highly asynchronous movement of fluorescent filaments
      through the bleached regions at peak rates of up to 2.8 microm/s. The kinetics of
      movement were very similar to our previous observations on neurofilaments moving
      through naturally occurring gaps, which indicates that the movement was not
      impaired by the photobleaching process. These results demonstrate that
      fluorescence photobleaching can be used to study the slow axonal transport of
      cytoskeletal polymers, but only if the experimental strategy is designed to
      ensure that rapid asynchronous movements can be detected. This may explain the
      failure of previous photobleaching studies to reveal the movement of
      neurofilament proteins and other cytoskeletal proteins in axons.

PMID- 11598208
TI  - RhoA-dependent switch between alpha2beta1 and alpha3beta1 integrins is induced by
      laminin-5 during early stage of HT-29 cell differentiation.
AB  - Integrin-mediated interactions between the basement membrane and epithelial cells
      control the differentiation of epithelia. We characterized the modulation of
      adhesive behaviors to basement membrane proteins and of integrin function in the
      human colon adenocarcinoma HT-29 cell line, which differentiates into enterocytes
      after the substitution of galactose for glucose in the medium. We demonstrate an
      increased capability of these cells to adhere to collagen type IV during the
      early stage of differentiation. This effect occurs without any changes in
      integrin cell surface expression but rather results from an
      alpha2beta1/alpha3beta1 integrin switch, alpha3beta1 integrin becoming the major
      collagen receptor. The increase in laminin-5 secretion and deposit on the matrix
      is a key factor in the mechanism regulating cell adhesion, because it is
      responsible for the activation of alpha3beta1 integrin. Furthermore, down
      regulation of RhoA GTPase activity occurs during HT-29 cell differentiation and
      correlates with the activation of the integrin alpha3beta1. Indeed, C3
      transferase, a RhoA GTPase inhibitor, induces a similar alpha2beta1/alpha3beta1
      switch in undifferentiated HT-29 cells. These results indicate that the decrease
      in RhoA activation is the biochemical mechanism underlying this integrin switch
      observed during cell differentiation. The physiological relevance of such
      modulation of integrin activity in the functioning of the crypt-villus axis is
      discussed.

PMID- 11598211
TI  - My science pilgrimage.

PMID- 11598210
TI  - The GPI transamidase complex of Saccharomyces cerevisiae contains Gaa1p, Gpi8p,
      and Gpi16p.
AB  - Gpi8p and Gaa1p are essential components of the GPI transamidase that adds
      glycosylphosphatidylinositols (GPIs) to newly synthesized proteins. After
      solubilization in 1.5% digitonin and separation by blue native PAGE, Gpi8p is
      found in 430-650-kDa protein complexes. These complexes can be affinity purified
      and are shown to consist of Gaa1p, Gpi8p, and Gpi16p (YHR188c). Gpi16p is an
      essential N-glycosylated transmembrane glycoprotein. Its bulk resides on the
      lumenal side of the ER, and it has a single C-terminal transmembrane domain and a
      small C-terminal, cytosolic extension with an ER retrieval motif. Depletion of
      Gpi16p results in the accumulation of the complete GPI lipid CP2 and of
      unprocessed GPI precursor proteins. Gpi8p and Gpi16p are unstable if either of
      them is removed by depletion. Similarly, when Gpi8p is overexpressed, it largely
      remains outside the 430-650-kDa transamidase complex and is unstable.
      Overexpression of Gpi8p cannot compensate for the lack of Gpi16p. Homologues of
      Gpi16p are found in all eucaryotes. The transamidase complex is not associated
      with the Sec61p complex and oligosaccharyltransferase complex required for ER
      insertion and N-glycosylation of GPI proteins, respectively. When GPI precursor
      proteins or GPI lipids are depleted, the transamidase complex remains intact.

PMID- 11598212
TI  - A change of heart. Finding the right balance.

PMID- 11598209
TI  - Simultaneous tyrosine and serine phosphorylation of STAT3 transcription factor is
      involved in Rho A GTPase oncogenic transformation.
AB  - Stats (signal transducers and activators of transcription) are latent cytoplasmic
      transcription factors that on a specific stimulus migrate to the nucleus and
      exert their transcriptional activity. Here we report a novel signaling pathway
      whereby RhoA can efficiently modulate Stat3 transcriptional activity by inducing
      its simultaneous tyrosine and serine phosphorylation. Tyrosine phosphorylation is
      exerted via a member of the Src family of kinases (SrcFK) and JAK2, whereas the
      JNK pathway mediates serine phosphorylation. Furthermore, cooperation of both
      tyrosine as well as serine phosphorylation is necessary for full activation of
      Stat3. Induction of Stat3 activity depends on the effector domain of RhoA and
      correlates with induction of both Src Kinase-related and JNK activities.
      Activation of Stat3 has biological implications. Coexpression of an oncogenic
      version of RhoA along with the wild-type, nontransforming Stat3 gene,
      significantly enhances its oncogenic activity on human HEK cells, suggesting that
      Stat3 is an essential component of RhoA-mediated transformation. In keeping with
      this, dominant negative Stat3 mutants or inhibition of its tyrosine or serine
      phosphorylation completely abrogate RhoA oncogenic potential. Taken together,
      these results indicate that Stat3 is an important player in RhoA-mediated
      oncogenic transformation, which requires simultaneous phosphorylation at both
      tyrosine and serine residues by specific signaling events triggered by RhoA
      effectors.

PMID- 11598213
TI  - Cell walls at the plant surface behave mechanically like fiber-reinforced
      composite materials.

PMID- 11598214
TI  - Development and characterization of genome-wide single nucleotide polymorphism
      markers in the green alga Chlamydomonas reinhardtii.

PMID- 11598215
TI  - Symbiotic nitrogen fixation and phosphorus acquisition. Plant nutrition in a
      world of declining renewable resources.

PMID- 11598216
TI  - The organization of cytoplasmic ribosomal protein genes in the Arabidopsis
      genome.
AB  - Eukaryotic ribosomes are made of two components, four ribosomal RNAs, and
      approximately 80 ribosomal proteins (r-proteins). The exact number of r-proteins
      and r-protein genes in higher plants is not known. The strong conservation in
      eukaryotic r-protein primary sequence allowed us to use the well-characterized
      rat (Rattus norvegicus) r-protein set to identify orthologues on the five haploid
      chromosomes of Arabidopsis. By use of the numerous expressed sequence tag (EST)
      accessions and the complete genomic sequence of this species, we identified 249
      genes (including some pseudogenes) corresponding to 80 (32 small subunit and 48
      large subunit) cytoplasmic r-protein types. None of the r-protein genes are
      single copy and most are encoded by three or four expressed genes, indicative of
      the internal duplication of the Arabidopsis genome. The r-proteins are
      distributed throughout the genome. Inspection of genes in the vicinity of r
      protein gene family members confirms extensive duplications of large chromosome
      fragments and sheds light on the evolutionary history of the Arabidopsis genome.
      Examination of large duplicated regions indicated that a significant fraction of
      the r-protein genes have been either lost from one of the duplicated fragments or
      inserted after the initial duplication event. Only 52 r-protein genes lack a
      matching EST accession, and 19 of these contain incomplete open reading frames,
      confirming that most genes are expressed. Assessment of cognate EST numbers
      suggests that r-protein gene family members are differentially expressed.

PMID- 11598217
TI  - Xylem water content and wood density in spruce and oak trees detected by high
      resolution computed tomography.
AB  - Elucidation of the mechanisms involved in long-distance water transport in trees
      requires knowledge of the water distribution within the sapwood and heartwood of
      the stem as well as of the earlywood and latewood of an annual ring. X-ray
      computed tomography is a powerful tool for measuring density distributions and
      water contents in the xylem with high spatial resolution. Ten- to 20-year-old
      spruce (Picea abies L. KARST.) and oak (Quercus robur) trees grown in the field
      were used throughout the experiments. Stem and branch discs were collected from
      different tree heights, immediately deep frozen, and used for the tomographic
      determinations of spatial water distributions. Results are presented for single
      tree individuals, demonstrating heartwood and sapwood distribution throughout
      their entire length as well as the water relations in single annual rings of both
      types of wood. Tree rings of the sapwood show steep water gradients from latewood
      to earlywood, whereas those of the heartwood reflect water deficiency in both
      species. Although only the latest two annual rings of the ringporous species are
      generally assumed to transport water, we found similar amounts of water and no
      tyloses in all rings of the oak sapwood, which indicates that at least water
      storage is important in the whole sapwood.

PMID- 11598218
TI  - Low ascorbic acid in the vtc-1 mutant of Arabidopsis is associated with decreased
      growth and intracellular redistribution of the antioxidant system.
AB  - Ascorbic acid has numerous and diverse roles in plant metabolism. We have used
      the vtc-1 mutant of Arabidopsis, which is deficient in ascorbate biosynthesis, to
      investigate the role of ascorbate concentration in growth, regulation of
      photosynthesis, and control of the partitioning of antioxidative enyzmes. The
      mutant possessed 70% less ascorbate in the leaves compared with the wild type.
      This lesion was associated with a slight increase in total glutathione but no
      change in the redox state of either ascorbate or glutathione. In vtc-1, total
      ascorbate in the apoplast was decreased to 23% of the wild-type value. The mutant
      displayed much slower shoot growth than the wild type when grown in air or at
      high CO(2) (3 mL L(-1)), where oxidative stress is diminished. Leaves were
      smaller, and shoot fresh weight and dry weight were lower in the mutant. No
      significant differences in the light saturation curves for CO(2) assimilation
      were found in air or at high CO(2), suggesting that the effect on growth was not
      due to decreased photosynthetic capacity in the mutant. Analysis of chlorophyll a
      fluorescence quenching revealed only a slight effect on non-photochemical energy
      dissipation. Hydrogen peroxide contents were similar in the leaves of the vtc-1
      mutant and the wild type. Total leaf peroxidase activity was increased in the
      mutant and compartment-specific differences in ascorbate peroxidase (APX)
      activity were observed. In agreement with the measurements of enzyme activity,
      the expression of cytosolic APX was increased, whereas that for chloroplast APX
      isoforms was either unchanged or slightly decreased. These data implicate
      ascorbate concentration in the regulation of the compartmentalization of the
      antioxidant system in Arabidopsis.

PMID- 11598219
TI  - Tomato ribonuclease LX with the functional endoplasmic reticulum retention motif
      HDEF is expressed during programmed cell death processes, including xylem
      differentiation, germination, and senescence.
AB  - We have studied the subcellular localization of the acid S-like ribonuclease
      (RNase) LX in tomato (Lycopersicon esculentum Mill.) cells using a combination of
      biochemical and immunological methods. It was found that the enzyme, unexpectedly
      excluded from highly purified vacuoles, accumulates in the endoplasmic reticulum.
      The evidence that RNase LX is a resident of the endoplasmic reticulum (ER) is
      supported by an independent approach showing that the C-terminal peptide HDEF of
      RNase LX acts as an alternative ER retention signal in plants. For functional
      testing, the cellular distribution of chimeric protein constructs based on a
      marker protein, Brazil nut (Bertholletia excelsa) 2S albumin, was analyzed
      immunochemically in transgenic tobacco (Nicotiana tabacum) plants. Here, we
      report that the peptide motif is necessary and sufficient to accumulate 2S
      albumin constructs of both vacuolar and extracellular final destinations in the
      ER. We have shown immunochemically that RNase LX is specifically expressed during
      endosperm mobilization and leaf and flower senescence. Using immunofluorescence,
      RNase LX protein was detected in immature tracheary elements, suggesting a
      function in xylem differentiation. These results support a physiological function
      of RNase LX in selective cell death processes that are also thought to involve
      programmed cell death. It is assumed that RNase LX accumulates in an ER-derived
      compartment and is released by membrane disruption into the cytoplasma of those
      cells that are intended to undergo autolysis. These processes are accompanied by
      degradation of cellular components supporting a metabolic recycling function of
      the intracellular RNase LX.

PMID- 11598220
TI  - Control of specific gene expression by gibberellin and brassinosteroid.
AB  - We identified a recessive, brassinolide-insensitive mutant caused by a deletion
      allele (bri1-201) of the brassinosteroid (BR) receptor BRI1. The bri1-201 mutant
      displayed altered expression levels of genes differentially regulated by
      gibberellin (GA). RNA-blot analysis revealed that BR and GA antagonistically
      regulate the accumulation of mRNAs of the GA-responsive GASA1 gene, as well as
      the GA-repressible GA5 gene. Expression studies with cycloheximide indicated that
      the antagonistic effects of GA and BR on GA5 require de novo protein synthesis.
      Reporter transgene analyses and RNA-blot analysis showed that BR and GA modulate
      GA5 expression, at least in part, at the transcriptional level, and that the
      signals are independent and subtractive.

PMID- 11598221
TI  - Biochemical and genetic analysis of the effects of amylose-extender mutation in
      rice endosperm.
AB  - Biochemical analysis of amylose-extender (ae) mutant of rice (Oryza sativa)
      revealed that the mutation in the gene for starch-branching enzyme IIb (BEIIb)
      specifically altered the structure of amylopectin in the endosperm by reducing
      short chains with degree of polymerization of 17 or less, with the greatest
      decrease in chains with degree of polymerization of 8 to 12. The extent of such
      change was correlated with the gelatinization properties of the starch granules,
      as determined in terms of solubility in urea solution. The ae mutation caused a
      dramatic reduction in the activity of BEIIb. The activity of soluble starch
      synthase I (SSI) in the ae mutant was significantly lower than in the wild type,
      suggesting that the mutation had a pleiotropic effect on the SSI activity. In
      contrast, the activities of BEI, BEIIa, ADP-Glc pyrophosphorylase, isoamylase,
      isoamylase, pullulanase, and Suc synthase were not affected by the mutation.
      Therefore, it is stressed that the function of BEIIb cannot be complemented by
      BEIIa and BEI. These results strongly suggest that BEIIb plays a specific role in
      the transfer of short chains, which might then be extended by SS to form the A
      and B(1) chains of amylopectin cluster in rice endosperm.

PMID- 11598222
TI  - Dominant negative guard cell K+ channel mutants reduce inward-rectifying K+
      currents and light-induced stomatal opening in arabidopsis.
AB  - Inward-rectifying potassium (K+(in)) channels in guard cells have been suggested
      to provide a pathway for K+ uptake into guard cells during stomatal opening. To
      test the proposed role of guard cell K+(in) channels in light-induced stomatal
      opening, transgenic Arabidopsis plants were generated that expressed dominant
      negative point mutations in the K+(in) channel subunit KAT1. Patch-clamp analyses
      with transgenic guard cells from independent lines showed that K+(in) current
      magnitudes were reduced by approximately 75% compared with vector-transformed
      controls at -180 mV, which resulted in reduction in light-induced stomatal
      opening by 38% to 45% compared with vector-transformed controls. Analyses of
      intracellular K+ content using both sodium hexanitrocobaltate (III) and elemental
      x-ray microanalyses showed that light-induced K+ uptake was also significantly
      reduced in guard cells of K+(in) channel depressor lines. These findings support
      the model that K+(in) channels contribute to K+ uptake during light-induced
      stomatal opening. Furthermore, transpirational water loss from leaves was reduced
      in the K+(in) channel depressor lines. Comparisons of guard cell K+(in) current
      magnitudes among four different transgenic lines with different K+(in) current
      magnitudes show the range of activities of K+(in) channels required for guard
      cell K+ uptake during light-induced stomatal opening.

PMID- 11598223
TI  - The maize CRINKLY4 receptor kinase controls a cell-autonomous differentiation
      response.
AB  - The maize (Zea mays) CRINKLY4 (cr4) gene encodes a receptor-like kinase that
      controls a variety of cell differentiation responses, particularly in the leaf
      epidermis and in the aleurone of the endosperm. In situ hybridization indicated
      that the cr4 transcript is present throughout the shoot apical meristem and young
      leaf primordia. A genetic mosaic analysis was conducted to test whether CR4
      signal transduction directly regulated the cellular processes associated with
      differentiation or whether differentiation was controlled through the production
      of a secondary signal. Genetic mosaics were created using gamma-rays to induce
      chromosome breakage in a cr4/Cr4+ heterozygote. The mutant cr4 allele was marked
      with the albino mutation, Oy-700. Breakage and loss of the chromosome arm
      carrying the wild-type alleles created a sector of albino, cr4 mutant tissue in
      an otherwise normal leaf. Analysis of such sectors indicated that cr4 functions
      cell autonomously to regulate cell morphogenesis, implying that CR4 signal
      transduction regulates cell differentiation through strictly intracellular
      functions and not the production of secondary intercellular signals. However,
      several sectors altered cell patterning in wild-type tissue adjacent to the
      sectors, suggesting that cr4 mutant cells are defective in the production of
      other lateral signals.

PMID- 11598224
TI  - External Ca(2+) is essential for chloroplast movement induced by mechanical
      stimulation but not by light stimulation.
AB  - In the fern Adiantum capillus-veneris, chloroplast movement is induced by
      mechanical stimulation as well as by light stimulation. Directional movement of
      both types depends on an actin-based motile system. To investigate the
      physiological relationship between mechanical and light signaling in the
      regulation of chloroplast movement, we examined the mechano-response of
      chloroplasts whose motility had been already restricted after photo-relocation.
      Chloroplast mechano-avoidance movement was induced under all of the photo
      relocation conditions tested, indicating that mechano-specific signals generated
      by mechanical stimulation dominate over the light signals and reactivate the
      motility of chloroplasts. When the effects of external Ca(2+) on the induction of
      mechano- and light responses were examined, strikingly different requirements of
      external Ca(2+) were found for each. In medium without Ca(2+), the mechano
      response was suppressed but no effects were observed on photo-response. Mechano
      relocation movement of chloroplasts was inhibited by 100 microM lanthanum
      (La(3+)), a plasma membrane calcium channel blocker, and by 10 microM gadolinium
      (Gd(3+)), a stretch-activated channel blocker. However, the same concentrations
      of these drugs did not affect the photo-relocation movement at all. These results
      suggest that the influx of external Ca(2+) is crucial for the early signaling
      step of chloroplast mechano-relocation but not for that of photo-relocation. This
      is the first report showing the separation of signaling pathways in mechano- and
      photo-relocation of chloroplasts.

PMID- 11598225
TI  - Effects of P(SAG12)-IPT gene expression on development and senescence in
      transgenic lettuce.
AB  - An ipt gene under control of the senescence-specific SAG12 promoter from
      Arabidopsis (P(SAG12)-IPT) significantly delayed developmental and postharvest
      leaf senescence in mature heads of transgenic lettuce (Lactuca sativa L. cv
      Evola) homozygous for the transgene. Apart from retardation of leaf senescence,
      mature, 60-d-old plants exhibited normal morphology with no significant
      differences in head diameter or fresh weight of leaves and roots. Induction of
      senescence by nitrogen starvation rapidly reduced total nitrogen, nitrate, and
      growth of transgenic and azygous (control) plants, but chlorophyll was retained
      in the lower (outer) leaves of transgenic plants. Harvested P(SAG12)-IPT heads
      also retained chlorophyll in their lower leaves. During later development
      (bolting and preflowering) of transgenic plants, the decrease in chlorophyll,
      total protein, and Rubisco content in leaves was abolished, resulting in a
      uniform distribution of these components throughout the plants. Homozygous
      P(SAG12)-IPT lettuce plants showed a slight delay in bolting (4-6 d), a severe
      delay in flowering (4-8 weeks), and premature senescence of their upper leaves.
      These changes correlated with significantly elevated concentrations of cytokinin
      and hexoses in the upper leaves of transgenic plants during later stages of
      development, implicating a relationship between cytokinin and hexose
      concentrations in senescence.

PMID- 11598226
TI  - Environmental and developmental regulation of the wound-induced cell wall protein
      WI12 in the halophyte ice plant.
AB  - A wounded gene WI12 was used as a marker to examine the interaction between
      biotic stress (wounding) and abiotic stress (high salt) in the facultative
      halophyte ice plant (Mesembryanthemum crystallinum). The deduced WI12 amino acid
      sequence has 68% similarity to WUN1, a known potato (Solanum tuberosum) wound
      induced protein. Wounding, methyl jasmonate, and pathogen infection induced local
      WI12 expression. Upon wounding, the expression of WI12 reached a maximum level
      after 3 h in 4-week-old juvenile leaves, whereas the maximum expression was after
      24 h in 8-week-old adult leaves. The temporal expression of WI12 in salt-stressed
      juvenile leaves was similar to that of adult leaves. The result suggests that a
      salt-induced switch from C3 to Crassulacean acid metabolism has a great influence
      on the ice plant's response to wounding. The expression of WI12 and the
      accumulation of WI12 protein were constitutively found in phloem and in wounded
      mesophyll cells. At the reproductive stage, WI12 was constitutively found in
      petals and styles, and developmentally regulated in the placenta and developing
      seeds. The histochemical analysis showed that the appearance of WI12 is
      controlled by both environmental and developmental factors. Immunogold labeling
      showed WI12 preferentially accumulates in the cell wall, suggesting its role in
      the reinforcement of cell wall composition after wounding and during plant
      development.

PMID- 11598227
TI  - Cellulose in cyanobacteria. Origin of vascular plant cellulose synthase?
AB  - Although cellulose biosynthesis among the cyanobacteria has been suggested
      previously, we present the first conclusive evidence, to our knowledge, of the
      presence of cellulose in these organisms. Based on the results of x-ray
      diffraction, electron microscopy of microfibrils, and cellobiohydrolase I-gold
      labeling, we report the occurrence of cellulose biosynthesis in nine species
      representing three of the five sections of cyanobacteria. Sequence analysis of
      the genomes of four cyanobacteria revealed the presence of multiple amino acid
      sequences bearing the DDD35QXXRW motif conserved in all cellulose synthases.
      Pairwise alignments demonstrated that CesAs from plants were more similar to
      putative cellulose synthases from Anabaena sp. Pasteur Culture Collection 7120
      and Nostoc punctiforme American Type Culture Collection 29133 than any other
      cellulose synthases in the database. Multiple alignments of putative cellulose
      synthases from Anabaena sp. Pasteur Culture Collection 7120 and N. punctiforme
      American Type Culture Collection 29133 with the cellulose synthases of other
      prokaryotes, Arabidopsis, Gossypium hirsutum, Populus alba x Populus tremula,
      corn (Zea mays), and Dictyostelium discoideum showed that cyanobacteria share an
      insertion between conserved regions U1 and U2 found previously only in eukaryotic
      sequences. Furthermore, phylogenetic analysis indicates that the cyanobacterial
      cellulose synthases share a common branch with CesAs of vascular plants in a
      manner similar to the relationship observed with cyanobacterial and chloroplast
      16s rRNAs, implying endosymbiotic transfer of CesA from cyanobacteria to plants
      and an ancient origin for cellulose synthase in eukaryotes.

PMID- 11598228
TI  - Assimilatory sulfate reduction in C(3), C(3)-C(4), and C(4) species of Flaveria.
AB  - The activity of the enzymes catalyzing the first two steps of sulfate
      assimilation, ATP sulfurylase and adenosine 5'-phosphosulfate reductase (APR),
      are confined to bundle sheath cells in several C(4) monocot species. With the aim
      to analyze the molecular basis of this distribution and to determine whether it
      was a prerequisite or a consequence of the C(4) photosynthetic mechanism, we
      compared the intercellular distribution of the activity and the mRNA of APR in
      C(3), C(3)-C(4), C(4)-like, and C(4) species of the dicot genus Flaveria.
      Measurements of APR activity, mRNA level, and protein accumulation in six
      Flaveria species revealed that APR activity, cysteine, and glutathione levels
      were significantly higher in C(4)-like and C(4) species than in C(3) and C(3)
      C(4) species. ATP sulfurylase and APR mRNA were present at comparable levels in
      both mesophyll and bundle sheath cells of C(4) species Flaveria trinervia.
      Immunogold electron microscopy demonstrated the presence of APR protein in
      chloroplasts of both cell types. These findings, taken together with results from
      the literature, show that the localization of assimilatory sulfate reduction in
      the bundle sheath cells is not ubiquitous among C(4) plants and therefore is
      neither a prerequisite nor a consequence of C(4) photosynthesis.

PMID- 11598229
TI  - Cell wall architecture of the elongating maize coleoptile.
AB  - The primary walls of grasses are composed of cellulose microfibrils,
      glucuronoarabinoxylans (GAXs), and mixed-linkage beta-glucans, together with
      smaller amounts of xyloglucans, glucomannans, pectins, and a network of
      polyphenolic substances. Chemical imaging by Fourier transform infrared
      microspectroscopy revealed large differences in the distributions of many
      chemical species between different tissues of the maize (Zea mays) coleoptile.
      This was confirmed by chemical analyses of isolated outer epidermal tissues
      compared with mesophyll-enriched preparations. Glucomannans and esterified uronic
      acids were more abundant in the epidermis, whereas beta-glucans were more
      abundant in the mesophyll cells. The localization of beta-glucan was confirmed by
      immunocytochemistry in the electron microscope and quantitative biochemical
      assays. We used field emission scanning electron microscopy, infrared
      microspectroscopy, and biochemical characterization of sequentially extracted
      polymers to further characterize the cell wall architecture of the epidermis.
      Oxidation of the phenolic network followed by dilute NaOH extraction widened the
      pores of the wall substantially and permitted observation by scanning electron
      microscopy of up to six distinct microfibrillar lamellae. Sequential chemical
      extraction of specific polysaccharides together with enzymic digestion of beta
      glucans allowed us to distinguish two distinct domains in the grass primary wall.
      First, a beta-glucan-enriched domain, coextensive with GAXs of low degrees of
      arabinosyl substitution and glucomannans, is tightly associated around
      microfibrils. Second, a GAX that is more highly substituted with arabinosyl
      residues and additional glucomannan provides an interstitial domain that
      interconnects the beta-glucan-coated microfibrils. Implications for current
      models that attempt to explain the biochemical and biophysical mechanism of wall
      loosening during cell growth are discussed.

PMID- 11598230
TI  - Why leaves turn red in autumn. The role of anthocyanins in senescing leaves of
      red-osier dogwood.
AB  - Why the leaves of many woody species accumulate anthocyanins prior to being shed
      has long puzzled biologists because it is unclear what effects anthocyanins may
      have on leaf function. Here, we provide evidence for red-osier dogwood (Cornus
      stolonifera) that anthocyanins form a pigment layer in the palisade mesophyll
      layer that decreases light capture by chloroplasts. Measurements of leaf
      absorbance demonstrated that red-senescing leaves absorbed more light of blue
      green to orange wavelengths (495-644 nm) compared with yellow-senescing leaves.
      Using chlorophyll a fluorescence measurements, we observed that maximum
      photosystem II (PSII) photon yield of red-senescing leaves recovered from a high
      light stress treatment, whereas yellow-senescing leaves failed to recover after 6
      h of dark adaptation, which suggests photo-oxidative damage. Because no
      differences were observed in light response curves of effective PSII photon yield
      for red- and yellow-senescing leaves, differences between red- and yellow
      senescing cannot be explained by differences in the capacities for photochemical
      and non-photochemical light energy dissipation. A role of anthocyanins as
      screening pigments was explored further by measuring the responses PSII photon
      yield to blue light, which is preferentially absorbed by anthocyanins, versus red
      light, which is poorly absorbed. We found that dark-adapted PSII photon yield of
      red-senescing leaves recovered rapidly following illumination with blue light.
      However, red light induced a similar, prolonged decrease in PSII photon yield in
      both red- and yellow-senescing leaves. We suggest that optical masking of
      chlorophyll by anthocyanins reduces risk of photo-oxidative damage to leaf cells
      as they senesce, which otherwise may lower the efficiency of nutrient retrieval
      from senescing autumn leaves.

PMID- 11598231
TI  - fw2.2 directly affects the size of developing tomato fruit, with secondary
      effects on fruit number and photosynthate distribution.
AB  - fw2.2 is a quantitative trait locus responsible for approximately 30% of the
      difference in fruit size between large, domesticated tomatoes (Lycopersicon
      esculentum Mill.) and their small-fruited wild relatives. The gene underlying
      this quantitative trait locus was cloned recently and shown to be associated with
      altered cell division in ovaries (Frary et al., 2000). However, it was not known
      whether the change in fruit size is associated with other changes in plant
      morphology or overall fruit yield-changes that could potentially cause the fruit
      weight phenotype. To shed light on this issue, a detailed comparison was made
      between nearly isogenic lines differing for alleles at this locus to search for
      pleiotropic effects associated with fw2.2. Field observations show that although
      the small-fruited nearly isogenic line produced smaller ovaries and fruit as
      expected, this was compensated by a larger number of fruit-due mainly to a
      significantly greater number of inflorescences-but with no net change in total
      fruit mass yield. This strongly suggests that fw2.2 may have a pleiotropic effect
      on how the plant distributes photosynthate among fruit. In a flower removal
      experiment to control for differences in inflorescence size and number, fruit
      size remained significantly different between the nearly isogenic lines. These
      observations indicate that the primary effect of fw2.2 is in controlling ovary
      and fruit size, and that other associated phenotypic effects are secondary.

PMID- 11598233
TI  - Molecular control of acid phosphatase secretion into the rhizosphere of proteoid
      roots from phosphorus-stressed white lupin.
AB  - White lupin (Lupinus albus) grown under P deficiency displays a suite of highly
      coordinated adaptive responses. Included among these is secretion of copious
      amounts of acid phosphatase (APase). Although numerous reports document that
      plants secrete APases in response to P deficiency, little is known of the
      biochemical and molecular events involved in this process. Here we characterize
      the secreted APase protein, cDNA, and gene from white lupin. The secreted APase
      enzyme is a glycoprotein with broad substrate specificity. It is synthesized as a
      preprotein with a deduced M(r) of 52,000 containing a 31-amino acid presequence.
      Analysis of the presequence predicts that the protein is targeted to outside the
      cell. The processed protein has a predicted M(r) of 49,000 but migrates as a
      protein with M(r) of 70,000 on sodium dodecyl sulfate gels. This is likely due to
      glycosylation. Enhanced expression is fairly specific to proteoid roots of P
      stressed plants and involves enhanced synthesis of both enzyme protein and mRNA.
      Secreted APase appears to be encoded by a single gene containing seven exons
      interrupted by six introns. The 5'-upstream putative promoter of the white lupin
      secreted APase contains a 50-base pair region having 72% identity to an
      Arabidopsis APase promoter that is responsive to P deficiency. The white lupin
      secreted APase promoter and targeting sequence may be useful tools for
      genetically engineering important proteins from plant roots.

PMID- 11598232
TI  - Biosynthetic pathway of insect juvenile hormone III in cell suspension cultures
      of the sedge Cyperus iria.
AB  - In most insect species, juvenile hormones regulate critical physiological
      processes such as metamorphosis and reproduction. In insects, these
      sesquiterpenoids are synthesized by retrocerebral endocrine organs, the corpora
      allata, via the classical mevalonate (MVA) pathway. One of these compounds,
      juvenile hormone III (JH III), has also been identified in the sedge Cyperus
      iria. In higher plants, biosynthesis of the sesquiterpenoid backbone may proceed
      through two distinct pathways: the MVA pathway or the 2C-methyl erythritol 4
      phosphate pathway or through a combination of both pathways. Cell suspension
      cultures of C. iria were used to elucidate the biosynthetic pathway of JH III in
      the plant. Enzyme inhibition and labeling studies conclusively demonstrated that
      the biosynthesis of the sesquiterpenoid backbone of JH III proceeds via the MVA
      pathway. Inhibitor and precursor feeding studies also suggest that later steps of
      JH III biosynthesis in C. iria are similar to the insect pathway and that the
      final enzymatic reaction in JH III biosynthesis is catalyzed by a cytochrome
      P(450) monooxygenase.

PMID- 11598234
TI  - Insertional mutants of Chlamydomonas reinhardtii that require elevated CO(2) for
      survival.
AB  - Aquatic photosynthetic organisms live in quite variable conditions of CO(2)
      availability. To survive in limiting CO(2) conditions, Chlamydomonas reinhardtii
      and other microalgae show adaptive changes, such as induction of a CO(2)
      concentrating mechanism, changes in cell organization, increased photorespiratory
      enzyme activity, induction of periplasmic carbonic anhydrase and specific
      polypeptides (mitochondrial carbonic anhydrases and putative chloroplast carrier
      proteins), and transient down-regulation in the synthesis of Rubisco. The signal
      for acclimation to limiting CO(2) in C. reinhardtii is unidentified, and it is
      not known how they sense a change of CO(2) level. The limiting CO(2) signals must
      be transduced into the changes in gene expression observed during acclimation, so
      mutational analyses should be helpful for investigating the signal transduction
      pathway for low CO(2) acclimation. Eight independently isolated mutants of C.
      reinhardtii that require high CO(2) for photoautotrophic growth were tested by
      complementation group analysis. These mutants are likely to be defective in some
      aspects of the acclimation to low CO(2) because they differ from wild type in
      their growth and in the expression patterns of five low CO(2)-inducible genes
      (Cah1, Mca1, Mca2, Ccp1, and Ccp2). Two of the new mutants formed a single
      complementation group along with the previously described mutant cia-5, which
      appears to be defective in the signal transduction pathway for low CO(2)
      acclimation. The other mutations represent six additional, independent
      complementation groups.

PMID- 11598235
TI  - Characterization of two cDNAs encoding mitochondrial lipoamide dehydrogenase from
      Arabidopsis.
AB  - In contrast to peas (Pisum sativum), where mitochondrial lipoamide dehydrogenase
      is encoded by a single gene and shared between the alpha-ketoacid dehydrogenase
      complexes and the Gly decarboxylase complex, Arabidopsis has two genes encoding
      for two mitochondrial lipoamide dehydrogenases. Northern-blot analysis revealed
      different levels of RNA expression for the two genes in different organs; mtLPD1
      had higher RNA levels in green leaves compared with the much lower level in
      roots. The mRNA for mtLPD2 shows the inverse pattern. The other organs examined
      showed nearly equal RNA expressions for both genes. Analysis of etiolated
      seedlings transferred to light showed a strong induction of RNA expression for
      mtLPD1 but only a moderate induction of mtLPD2. Based on the organ and light
      dependent expression patterns, we hypothesize that mtLPD1 encodes the protein
      most often associated with the Gly decarboxylase complex, and mtLPD2 encodes the
      protein incorporated into alpha-ketoacid dehydrogenase complexes. Due to the high
      level of sequence conservation between the two mtLPDs, we assume that the
      proteins, once in the mitochondrial matrix, are interchangeable among the
      different multienzyme complexes. If present at high levels, one mtLPD might
      substitute for the other. Supporting this hypothesis are results obtained with a
      T-DNA knockout mutant, mtlpd2, which shows no apparent phenotypic change under
      laboratory growth conditions. This indicates that mtLPD1 can substitute for
      mtLPD2 and associate with all these multienzyme complexes.

PMID- 11598236
TI  - Long-day induction of flowering in Lolium temulentum involves sequential
      increases in specific gibberellins at the shoot apex.
AB  - One challenge for plant biology has been to identify floral stimuli at the shoot
      apex. Using sensitive and specific gas chromatography-mass spectrometry
      techniques, we have followed changes in gibberellins (GAs) at the shoot apex
      during long day (LD)-regulated induction of flowering in the grass Lolium
      temulentum. Two separate roles of GAs in flowering are indicated. First, within 8
      h of an inductive LD, i.e. at the time of floral evocation, the GA(5) content of
      the shoot apex doubled to about 120 ng g(-1) dry weight. The concentration of
      applied GA(5) required for floral induction of excised apices (R.W. King, C.
      Blundell, L.T. Evans [1993] Aust J Plant Physiol 20: 337-348) was similar to that
      in the shoot apex. Leaf-applied [(2)H(4)] GA(5) was transported intact from the
      leaf to the shoot apex, flowering being proportional to the amount of GA(5)
      imported. Thus, GA(5) could be part of the LD stimulus for floral evocation of L.
      temulentum or, alternatively, its increase at the shoot apex could follow import
      of a primary floral stimulus. Later, during inflorescence differentiation and
      especially after exposure to additional LD, a second GA action was apparent. The
      content of GA(1) and GA(4) in the apex increased greatly, whereas GA(5) decreased
      by up to 75%. GA(4) applied during inflorescence differentiation strongly
      promoted flowering and stem elongation, whereas it was ineffective for earlier
      floral evocation although it caused stem growth at all times of application.
      Thus, we conclude that GA(1) and GA(4) are secondary, late-acting LD stimuli for
      inflorescence differentiation in L. temulentum.

PMID- 11598237
TI  - Photosystem II peripheral accessory chlorophyll mutants in Chlamydomonas
      reinhardtii. Biochemical characterization and sensitivity to photo-inhibition.
AB  - In addition to the four chlorophylls (Chls) involved in primary charge
      separation, the photosystem II (PSII) reaction center polypeptides, D1 and D2,
      coordinate a pair of symmetry-related, peripheral accessory Chls. These Chls are
      axially coordinated by the D1-H118 and D2-H117 residues and are in close
      association with the proximal Chl antennae proteins, CP43 and CP47. To gain
      insight into the function(s) of each of the peripheral Chls, we generated site
      specific mutations of the amino acid residues that coordinate these Chls and
      characterized their energy and electron transfer properties. Our results
      demonstrate that D1-H118 and D2-H117 mutants differ with respect to: (a) their
      relative numbers of functional PSII complexes, (b) their relative ability to
      stabilize charge-separated states, (c) light-harvesting efficiency, and (d) their
      sensitivity to photo-inhibition. The D2-H117N and D2-H117Q mutants had reduced
      levels of functional PSII complexes and oxygen evolution capacity as well as
      reduced light-harvesting efficiencies relative to wild-type cells. In contrast,
      the D1-H118Q mutant was capable of near wild-type rates of oxygen evolution at
      saturating light intensities. The D1-H118Q mutant also was substantially more
      resistant to photo-inhibition than wild type. This reduced sensitivity to photo
      inhibition is presumably associated with a reduced light-harvesting efficiency in
      this mutant. Finally, it is noted that the PSII peripheral accessory Chls have
      similarities to a to a pair of Chls also present in the PSI reaction center
      complex.

PMID- 11598238
TI  - Expression of beta-expansins is correlated with internodal elongation in
      deepwater rice.
AB  - Fourteen putative rice (Oryza sativa) beta-expansin genes, Os-EXPB1 through Os
      EXPB14, were identified in the expressed sequence tag and genomic databases. The
      DNA and deduced amino acid sequences are highly conserved in all 14 beta
      expansins. They have a series of conserved C (cysteine) residues in the N
      terminal half of the protein, an HFD (histidine-phenylalanine-aspartate) motif in
      the central region, and a series of W (tryptophan) residues near the carboxyl
      terminus. Five beta-expansin genes are expressed in deepwater rice internodes,
      with especially high transcript levels in the growing region. Expression of four
      beta-expansin genes in the internode was induced by treatment with gibberellin
      and by wounding. The wound response resulted from excising stem sections or from
      piercing pinholes into the stem of intact plants. The level of wound-induced beta
      expansin transcripts declined rapidly 5 h after cutting of stem sections. We
      conclude that the expression of beta-expansin genes is correlated with rapid
      elongation of deepwater rice internodes, it is induced by gibberellin and
      wounding, and wound-induced beta-expansin mRNA appears to turn over rapidly.

PMID- 11598239
TI  - Multiple, distinct isoforms of sucrose synthase in pea.
AB  - Genes encoding three isoforms of sucrose synthase (Sus1, Sus2, and Sus3) have
      been cloned from pea (Pisum sativum). The genes have distinct patterns of
      expression in different organs of the plant, and during organ development.
      Studies of the isoforms expressed as recombinant proteins in Escherichia coli
      show that they differ in kinetic properties. Although not of great magnitude, the
      differences in properties are consistent with some differentiation of
      physiological function between the isoforms. Evidence for differentiation of
      function in vivo comes from the phenotypes of rug4 mutants of pea, which carry
      mutations in the gene encoding Sus1. One mutant line (rug4-c) lacks detectable
      Sus1 protein in both the soluble and membrane-associated fractions of the embryo,
      and Sus activity in the embryo is reduced by 95%. The starch content of the
      embryo is reduced by 30%, but the cellulose content is unaffected. The results
      imply that different isoforms of Sus may channel carbon from sucrose towards
      different metabolic fates within the cell.

PMID- 11598240
TI  - Sulfur economy and cell wall biosynthesis during sulfur limitation of
      Chlamydomonas reinhardtii.
AB  - We have identified two novel periplasmic/cell wall polypeptides that specifically
      accumulate during sulfur limitation of Chlamydomonas reinhardtii. These
      polypeptides, present at high levels in the extracellular polypeptide fraction
      from a sulfur-deprived, cell wall-minus C. reinhardtii strain, have apparent
      molecular masses of 76 and 88 kD and are designated Ecp76 and Ecp88. N-terminal
      sequences of these polypeptides facilitated the isolation of full-length Ecp76
      and Ecp88 cDNAs. Ecp76 and Ecp88 polypeptides are deduced to be 583 and 595 amino
      acids, respectively. Their amino acid sequences are similar to each other, with
      features characteristic of cell wall-localized hydroxyproline-rich glycoproteins;
      the N terminus of each polypeptide contains a predicted signal sequence, whereas
      the C terminus is rich in proline, alanine, and serine. Ecp76 and Ecp88 have
      either no (Ecp88) or one (Ecp76) sulfur-containing amino acid and transcripts
      encoding these polypeptides are not detected in cultures maintained on complete
      medium, but accumulate when cells are deprived of sulfur. This accumulation is
      temporally delayed relative to the accumulation of sulfur stress-induced
      arylsulfatase and ATP sulfurylase transcripts. The addition of sulfate back to
      sulfur-starved cultures caused a rapid decline in Ecp76 and Ecp88 mRNAs (half
      lives < 10 min). Furthermore, the C. reinhardtii sac1 mutant, which lacks a
      regulatory protein critical for acclimation to sulfur limitation, does not
      accumulate Ecp76 or Ecp88 transcripts. These results suggest that the Ecp76 and
      Ecp88 genes are under SacI control, and that restructuring of the C. reinhardtii
      cell wall during sulfur limitation may be important for redistribution of
      internal and efficient utilization of environmental sulfur-containing molecules.

PMID- 11598241
TI  - Characterization of a functional soluble form of a Brassica napus membrane
      anchored endo-1,4-beta-glucanase heterologously expressed in Pichia pastoris.
AB  - The Brassica napus gene, Cel16, encodes a membrane-anchored endo-1,4-beta
      glucanase with a deduced molecular mass of 69 kD. As for other membrane-anchored
      endo-1,4-beta-glucanases, Cel16 consists of a predicted intracellular, charged N
      terminus (methionine(1)-lysine(70)), a hydrophobic transmembrane domain
      (isoleucine(71)-valine(93)), and a periplasmic catalytic core (lysine(94)
      proline(621)). Here, we report the functional analysis of Delta(1-90)Cel16, the N
      terminally truncated Cel16, missing residues 1 through 90 and comprising the
      catalytic domain of Cel16 expressed recombinantly in the methylotrophic yeast
      Pichia pastoris as a soluble protein. A two-step purification protocol yielded
      Delta(1-90)Cel16 in a pure form. The molecular mass of Delta(1-90)Cel16, when
      determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was
      about 130 kD and about 60 kD after enzymatic removal of N-glycans, fitting the
      expected molecular mass of 59 kD. Delta(1-90)Cel16 was highly N glycosylated as
      compared with the native B. napus Cel16 protein. Delta(1-90)Cel16 had a pH
      optimum of 6.0. The activity of Delta(1-90)Cel16 was inhibited by EDTA and
      exhibited a strong dependence on calcium. Delta(1-90)Cel16 showed substrate
      specificity for low substituted carboxymethyl-cellulose and amorphous cellulose.
      It did not hydrolyze crystalline cellulose, xyloglycan, xylan, (1-->3),(1-->4)
      beta-D-glucan, the highly substituted hydroxyethylcellulose, or the
      oligosaccharides cellotriose, cellotetraose, cellopentaose, or xylopentaose. Size
      exclusion analysis of Delta(1-90)Cel16-hydrolyzed carboxymethylcellulose showed
      that Delta(1-90)Cel16 is a true endo-acting glucanase.

PMID- 11598243
TI  - The 2001 RadioGraphics monograph issue: abdominal imaging: continuing the
      partnership between radiologists and surgeons.

PMID- 11598242
TI  - Analysis of the compartmentation of glycolytic intermediates, nucleotides,
      sugars, organic acids, amino acids, and sugar alcohols in potato tubers using a
      nonaqueous fractionation method.
AB  - The compartmentation of metabolism in heterotrophic plant tissues is poorly
      understood due to the lack of data on metabolite distributions and fluxes between
      subcellular organelles. The main reason for this is the lack of suitable
      experimental methods with which intracellular metabolism can be measured. Here,
      we describe a nonaqueous fractionation method that allows the subcellular
      distributions of metabolites in developing potato (Solanum tuberosum L. cv
      Desiree) tubers to be calculated. In addition, we have coupled this fractionation
      method to a recently described gas chromatography-mass spectrometry procedure
      that allows the measurement of a wide range of small metabolites. To calculate
      the subcellular metabolite concentrations, we have analyzed organelle volumes in
      growing potato tubers using electron microscopy. The relative volume
      distributions in tubers are very similar to the ones for source leaves. More than
      60% of most sugars, sugar alcohols, organic acids, and amino acids were found in
      the vacuole, although the concentrations of these metabolites is often higher in
      the cytosol. Significant amounts of the substrates for starch biosynthesis,
      hexose phosphates, and ATP were found in the plastid. However, pyrophosphate was
      located almost exclusively in the cytosol. Calculation of the mass action ratios
      of sucrose synthase, UDP-glucose pyrophosphorylase, phosphoglucosisomerase, and
      phosphoglucomutase indicate that these enzymes are close to equilibrium in
      developing potato tubers. However, due to the low plastidic pyrophosphate
      concentration, the reaction catalyzed by ADP-glucose pyrophosphorylase was
      estimated to be far removed from equilibrium.

PMID- 11598244
TI  - From the RSNA refresher courses: CT angiography: clinical applications in the
      abdomen.
AB  - The development of spiral computed tomography (CT) and subsequently multidetector
      CT has provided unparalleled opportunities for advancement of CT technology and
      clinical applications. One of the most influential developments has been CT
      angiography, which is the use of thin-section CT combined with postprocessing of
      imaging data by using a variety of three-dimensional reconstruction techniques to
      produce vascular maps that equal or exceed those provided by classic angiography
      in many applications. In the evaluation of pancreatic disease, the use of
      multidetector CT angiography enables the radiologist to produce vascular maps
      that clearly show tumor invasion of vasculature and the relationship of vessels
      to pancreatic masses. Anatomic areas for which the three-dimensional display is
      especially helpful include the confluence of the portal vein and the superior
      mesenteric vein and the more distal portions of the portal vein. Preliminary
      studies indicate that CT angiography may prove beneficial in the evaluation of
      ischemic bowel and active Crohn disease. CT angiography has proved extremely
      valuable for applications such as preoperative planning for hepatic resection,
      preoperative evaluation and planning for liver transplantation, pretreatment
      planning for patients considered for hepatic arterial infusion chemotherapy, and
      pretreatment evaluation of portal vein patency for a variety of reasons. CT
      angiography can also provide supplemental information in patients with cirrhosis,
      upper gastrointestinal tract bleeding due to varices, or primary extrahepatic
      neoplasms.

PMID- 11598245
TI  - Essential techniques for successful radio-frequency thermal ablation of malignant
      hepatic tumors.
AB  - Radio-frequency thermal ablation is one of the most promising minimally invasive
      techniques for the treatment of nonresectable hepatic tumors. Essential technical
      tips to successful radio-frequency ablation therapy were collected from five
      international experts. They were organized into five categories: understanding
      the mechanisms and principles of radio-frequency ablation, modulation of tissue
      physiologic characteristics to increase tumor destruction, strategies of
      overlapping ablations, strategies to improve ablation according to tumor
      location, and imaging strategies after ablation to ensure adequate therapy.
      Established factors for optimal ablation, as well as emerging technical tips, are
      addressed with illustrations in each section. These essential tips will be very
      helpful for physicians performing radio-frequency ablation of hepatic tumors.

PMID- 11598247
TI  - Radio-frequency ablation of liver tumors: assessment of therapeutic response and
      complications.
AB  - An alternative to surgical resection of liver tumors, radio-frequency ablation
      induces in situ thermal coagulation necrosis through the delivery of high
      frequency alternating current to the tissues. Imaging helps to detect treatable
      lesions, guide the placement of the probe, and assess the effect of therapy.
      Computed tomography (CT) is used most frequently to determine whether the
      ablation is complete and to screen for early recurrences that may benefit from
      reablation. Complete ablation creates an area of necrosis that, at CT, is of low
      attenuation compared with the surrounding liver tissue, is often homogeneous, and
      has smooth margins. The most important features are the size of the necrotic
      defect, which, immediately after treatment, should be larger than that of the
      pretreatment tumor, and the sharpness of the margins, which indicates an abrupt
      change in attenuation between the necrotic tissue and surrounding liver tissue.
      Enhancement, when present, is due to perfusion abnormality or granulation tissue
      and forms a regular rim or a homogeneous zone at the margin of the defect. It is
      seen immediately after ablation but may be prolonged. Enhancement is affected by
      the scanning technique. Over time, the size of the defect remains stable or
      decreases. Any variation from this general pattern is suggestive of incomplete
      ablation or recurrence.

PMID- 11598248
TI  - Selection of patients for resection of hepatic metastases: improved detection of
      extrahepatic disease with FDG pet.
AB  - A rapidly emerging clinical application of positron emission tomography (PET) is
      the detection of tumor tissue at whole-body studies performed with the glucose
      analogue 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG). High rates of recurrence
      after partial hepatic resection in patients with colorectal cancer liver
      metastases indicate that current presurgical imaging strategies are failing to
      show extrahepatic tumor deposits. Although FDG PET cannot match the anatomic
      resolution of conventional imaging techniques in the liver and the lungs, it is
      particularly useful for identification and characterization of extrahepatic
      disease. FDG PET can show foci of metastatic disease that may not be apparent at
      conventional anatomic imaging and can aid in the characterization of
      indeterminate soft-tissue masses. Several sources of benign and physiologic
      increased activity at FDG PET emphasize the need for careful correlation with
      findings of other imaging studies and clinical findings. FDG PET can improve the
      selection of patients for partial hepatic resection and thereby reduce the
      morbidity and mortality associated with inappropriate surgery.

PMID- 11598249
TI  - Hepatic imaging with multidetector CT.
AB  - Combining the advantages of a multirow detector array with a fast gantry rotation
      time, multidetector computed tomographic (CT) scanners can acquire sections at a
      faster rate than was previously possible. As a result, multidetector CT permits
      scanning during multiple specific phases of intravenous contrast enhancement and
      the acquisition of very thin sections over a large area, allowing the creation of
      multiplanar reconstructions with high z-axis resolution. The authors present an
      imaging strategy for the diagnosis and staging of hepatic pathologic conditions
      that emphasizes the role of multidetector CT. Users must master several scanning
      parameters to obtain the best image quality. For hepatic CT, it is practical to
      use relatively narrow collimation, increasing the pitch as needed to cover the
      entire liver. The choice of reconstruction interval is dependent on the problem
      for which the study is being performed. Water is recommended as an oral contrast
      agent for non-axial reconstructions, since high-attenuation oral contrast agents
      might degrade them. Appropriate scanning delays for hepatic CT are dependent on
      the contrast-agent injection strategy used. A triple-pass technique, highlighting
      the arterial, parenchymal, and portal venous phases of enhancement, is
      recommended.

PMID- 11598250
TI  - Unusual hemodynamics and pseudolesions of the noncirrhotic liver at CT.
AB  - Recognition of pseudolesions of the liver at computed tomography (CT) is
      important because of their close resemblance to primary liver cancers or
      metastases. Two types of pseudolesion in the noncirrhotic liver include that due
      to transient extrinsic compression, typically caused by ribs or the diaphragm,
      and that due to a "third inflow" of blood from other than the usual hepatic
      arterial and portal venous sources: the cholecystic, parabiliary, or epigastric
      paraumbilical venous system. Although the location of both types of pseudolesion
      are characteristic, their appearances at CT during arterial portography and CT
      during selective angiography vary from nonenhanced low-attenuation areas to well
      enhanced high-attenuation areas, depending on the amount and timing of the inflow
      and presence or absence of focal metabolic alteration of the hepatocytes.
      Radiologists need to understand the underlying mechanism of these pseudolesions
      to better recognize the wide range of their appearances at CT.

PMID- 11598251
TI  - Radiologic spectrum of cholangiocarcinoma: emphasis on unusual manifestations and
      differential diagnoses.
AB  - Most cholangiocarcinomas are ductal adenocarcinomas that arise from both intra-
      and extrahepatic bile duct epithelium, and their typical growth pattern can be
      classified as exophytic, infiltrative, polypoid, or a combination of these. Those
      of unusual histologic type (eg, mucin-hypersecreting cholangiocarcinoma, squamous
      adenocarcinoma, biliary cystadenocarcinoma, and mucinous carcinoma) show a growth
      pattern different from that of the typical ones (ie, ductal). Cholangiocarcinomas
      frequently develop in patients with any of a variety of preexisting bile duct
      diseases, some of which are considered precursors of cholangiocarcinoma (eg,
      biliary lithiasis, clonorchiasis, recurrent pyogenic cholangitis, and primary
      sclerosing cholangitis). Some bulky hepatic tumors of either primary or secondary
      origin mimic exophytic peripheral cholangiocarcinoma. Some variants of
      hepatocellular carcinoma, such as sclerosing, fibrolamellar, and
      cholangiohepatocellular carcinoma, resemble exophytic peripheral
      cholangiocarcinoma, while that with intraductal growth resembles polypoid
      cholangiocarcinoma. Among benign bile duct diseases, tumorous conditions (eg,
      benign biliary tumors) may mimic polypoid cholangiocarcinoma, whereas benign
      stricture of various causes (eg, cholangitides, traumatic and postsurgical
      sequelae, chronic pancreatitis, papillary stenosis) usually mimics infiltrative
      cholangiocarcinoma.

PMID- 11598252
TI  - From the RSNA refresher courses: screening the cirrhotic liver for hepatocellular
      carcinoma with CT and MR imaging: opportunities and pitfalls.
AB  - The inherent distortion of the appearance of liver parenchyma by the underlying
      pathologic changes of cirrhosis can obscure and simulate malignancy at imaging.
      That hepatocellular carcinoma is the most common abdominal malignancy worldwide
      and occurs most often in patients with chronic liver disease and cirrhosis
      compounds this problem. Magnetic resonance (MR) imaging and, to a lesser extent,
      computed tomography (CT) can depict the underlying nodular and fibrotic changes
      in patients with cirrhosis, particularly when siderotic nodular regeneration is
      present. Application of state-of-the-art helical CT and MR imaging techniques has
      improved the ability to detect hepatocellular carcinoma in this population, but,
      even with these advances, fewer than 50% of small tumors are detected with either
      of these techniques in a screening population. Dynamic hepatic arterial-phase
      contrast material-enhanced imaging is essential with both CT and MR imaging to
      achieve even these levels of success. Benign lesions that simulate tumor tissue
      are encountered in many patients with cirrhosis and include focal fibrosis,
      infarcted regenerative nodules, arteriovenous shunts, hemangiomas,
      pseudoaneurysms, and focal transient hepatic enhancement. An awareness of the
      imaging characteristics of these lesions can help one avoid a mistaken diagnosis
      of hepatocellular carcinoma in many cases.

PMID- 11598253
TI  - Liver transplantation: preoperative CT evaluation.
AB  - Liver transplantation is a successful therapeutic option for patients with
      chronic liver disease and liver failure in that 1-year survival is greater than
      80%. Orthotopic transplantation is usually performed from a cadaveric or living
      adult donor. The necessary evaluation of recipients and donors prior to
      transplantation can be successfully performed with computed tomography (CT). CT
      is useful in determining clinically relevant information for recipients such as
      size of the caudate lobe, exclusion of advanced hepatocellular carcinoma and
      other malignancy, patency of the venous system, presence of perihepatic varices,
      patency of the celiac artery, exclusion of splenic artery aneurysm, and position
      of iatrogenic venous shunts. CT in living donors may help to determine clinically
      relevant information about variant hepatic arterial anatomy, source of the artery
      to segment IV, intraparenchymal anatomy of the hepatic veins and accessory
      hepatic veins, trifurcation of the portal vein or hepatic duct, liver volume, and
      fatty change of the parenchyma. Surgical approaches and the imaging findings that
      influence management are reviewed.

PMID- 11598254
TI  - CT of the duodenum: an overlooked segment gets its due.
AB  - Abdominal computed tomography (CT) is frequently performed to evaluate
      gastrointestinal pathologic conditions, and the majority of the gastrointestinal
      radiology literature has concentrated on the colon, stomach, and distal small
      bowel. In a description of CT findings of duodenal pathologic conditions,
      congenital, traumatic, inflammatory, and neoplastic diseases are presented.
      Congenital duodenal anomalies such as duplications and diverticula are usually
      asymptomatic, while annular pancreas and malrotation may manifest in the 1st
      decade of life. CT plays a vital role in the diagnosis of traumatic duodenal
      injury. Primary inflammatory processes of the duodenum such as ulcers and
      secondary involvement from pancreatitis can reliably be diagnosed at CT.
      Infectious diseases of the duodenum are difficult to diagnose, as the findings
      are not specific. While small bowel malignancies are relatively rare, lipoma,
      adenoma, and adenocarcinoma, as well as local extension from adjacent
      malignancies, can be diagnosed at CT. Careful CT technique and attention to the
      duodenum can result in reliable prospective diagnoses.

PMID- 11598255
TI  - MR enteroclysis imaging of Crohn disease.
AB  - Magnetic resonance (MR) enteroclysis imaging is emerging as a technique for
      evaluation of the small bowel in patients with Crohn disease. Administration of
      1.5-2 L of isosmotic water solution through a nasojejunal catheter ensures
      distention of the bowel and facilitates identification of wall abnormalities.
      True fast imaging with steady-state precession (FISP), half-Fourier acquisition
      single-shot turbo spin-echo (HASTE), and postgadolinium T1-weighted three
      dimensional fast low-angle shot sequences can be employed in a comprehensive and
      integrated MR enteroclysis examination protocol to overcome specific
      disadvantages of each of the sequences involved. Superficial abnormalities that
      are ideally delineated with conventional enteroclysis are not consistently
      depicted with MR enteroclysis. The characteristic transmural abnormalities of
      Crohn disease such as bowel wall thickening, linear ulcers, and cobblestoning are
      accurately shown with MR enteroclysis imaging, especially with the true FISP
      sequence. MR enteroclysis is comparable to conventional enteroclysis in the
      detection of the number and extent of involved small bowel segments and in the
      disclosure of luminal narrowing or prestenotic intestinal dilatation. The
      clinical utility of MR enteroclysis in Crohn disease has not been fully
      established. At present, the method may be used for follow-up studies of known
      disease, estimation of disease activity, and determination of the extramucosal
      extent and spread of the disease process.

PMID- 11598256
TI  - Peroxide-enhanced anal endosonography: technique, image interpretation, and
      clinical applications.
AB  - Because current techniques for examination and imaging of perianal fistulas tend
      to underestimate the extent, location, and course of perianal fistulas-
      information essential for decisions about surgical management--the use of
      hydrogen peroxide was investigated as an image-enhancing contrast agent for
      confirmation of the presence of and improvement in the depiction of fistulas
      during endoanal ultrasonography (US). After conventional endoanal US was
      performed with a side-fire 7.5- or 10.0-MHz rotating endoprobe, external perianal
      openings were cannulated and approximately 1 mL of peroxide was administered.
      After reinsertion of the endoprobe, the entire course of the echogenic fistula,
      including its relation to the internal and external sphincters and the levator
      ani muscle, was depicted in real time in three dimensions. This depiction of
      fistulas permits accurate classification, which facilitates surgical planning. In
      experience with more than 60 patients, peroxide-enhanced endoanal US was found to
      be a useful technique for documentation of the presence, number, and internal
      course of perianal fistulas and for characterization of abnormalities seen at
      endosonography performed without use of contrast enhancement. In addition, the
      technique permitted surgeons to stratify patients into treatment groups and has
      been especially useful for planning surgical treatments.

PMID- 11598257
TI  - From the RSNA refresher courses: focused abdominal US for trauma.
AB  - Focused abdominal ultrasonography (US) has been introduced in Europe as a method
      to evaluate blunt abdominal trauma. The main focus of the examination is
      detection of free fluid in the abdomen secondary to injury of the abdominal
      organs. The examination takes only a few minutes to perform. In the authors'
      experience, trauma patients in unstable condition and in whom significant free
      fluid is detected are immediately taken to the operating room for surgical
      exploration without undergoing computed tomographic (CT) correlation. The authors
      have also used US to identify the specific site of organ injury. Injuries to
      solid organs such as the liver, spleen, and kidney that are identified with US
      usually appear heterogeneous or hyperechoic. A hematoma surrounding the injured
      organ may appear echogenic or hypoechoic. However, pitfalls of focused abdominal
      US for trauma include failure to show contained solid-organ injuries; injuries to
      the diaphragm, pancreas, and adrenal gland; and some bowel injuries. Thus,
      negative findings at US do not exclude an intraperitoneal injury, and close
      clinical observation or CT is warranted.

PMID- 11598258
TI  - Ct findings in blunt renal trauma.
AB  - Computed tomography (CT) can provide essential anatomic and physiologic
      information required to determine management of intraabdominal and
      retroperitoneal injuries sustained during blunt abdominal trauma. It can help in
      evaluation of the type and severity of parenchymal injury, the extent of
      perirenal hemorrhage and parenchymal devascularization, and the presence of
      urinary extravasation. CT can help confirm the presence of major injuries to the
      vascular pedicle and depict occult renal pathologic conditions. Principal
      indications for the use of CT in the evaluation of blunt renal trauma include (a)
      the presence of gross hematuria, (b) microscopic hematuria associated with shock
      (systolic blood pressure <90 mm Hg), and (c) microscopic hematuria associated
      with a positive result of diagnostic peritoneal lavage. The majority of renal
      injuries sustained during blunt abdominal trauma are contusions and minor
      parenchymal lacerations amenable to nonoperative management. Deep parenchymal
      lacerations, urinary extravasation, and mild to moderate degrees of parenchymal
      devascularization may also be treated conservatively. Radiologists should look
      for coexisting renal lesions such as tumors and traumatic false aneurysms that
      may alter management.

PMID- 11598259
TI  - Evaluation of prospective living renal donors for laparoscopic nephrectomy with
      multisection CT: the marriage of minimally invasive imaging with minimally
      invasive surgery.
AB  - Laparoscopic technique for excision of a kidney from a living donor has
      advantages over conventional open surgery, but operative visibility and surgical
      exposure are limited. Preoperative multisection computed tomography (CT) can
      provide necessary anatomic information in a minimally invasive procedure. A three
      phase examination is suggested: (a) imaging from the top of the kidneys to the
      pubic symphysis with a section width of 2.5 mm and no contrast medium, (b)
      scanning of the kidneys and upper pelvis during the arterial phase of enhancement
      with a section width of 1.0 mm, and (c) scanning of the kidneys and upper
      retroperitoneum during the nephrographic phase of enhancement with a section
      width of 1.0 mm. Emphasis in this article is placed on analysis of the venous
      anatomy because most radiologists are unfamiliar with the anatomic variations.
      Conventional radiography of the abdomen and pelvis is performed after CT to
      evaluate the collecting system and ureters and to provide a lower total radiation
      dose than if CT were used. Of several postprocessing techniques that may be used,
      the authors prefer maximum intensity projection for arterial evaluation and
      multiplanar reformatting for venous evaluation.

PMID- 11598260
TI  - Current concepts in the diagnosis and management of renal cell carcinoma: role of
      multidetector ct and three-dimensional CT.
AB  - Renal cell carcinoma is the most common primary tumor of the kidney, with more
      than 30,000 new cases diagnosed in the United States each year. With the
      widespread use of cross-sectional imaging, many tumors are detected incidentally.
      Single- and multidetector computed tomography (CT) have helped refine the
      diagnostic work-up of renal masses by allowing image acquisition in various
      phases of renal enhancement after intravenous administration of a single bolus of
      contrast material. The scanning protocol should include unenhanced CT followed by
      imaging during the corticomedullary and nephrographic phases of enhancement. The
      nephrographic phase is the most sensitive for tumoral detection, while the
      corticomedullary phase is essential for imaging the renal veins for possible
      tumoral extension and the parenchymal organs for potential metastases. Knowledge
      of the tumoral stage at the time of diagnosis is essential for prognosis and
      surgical planning. The accuracy of CT for staging has been reported to reach 91%,
      with most staging errors related to the diagnosis of perinephric extension of
      tumor. Three-dimensional CT provides the urologist with an interactive road map
      of the relationships among the tumor, the major vessels, and the collecting
      system. This information is particularly critical if the tumor extends into the
      inferior vena cava and if nephron-sparing surgery is being planned.

PMID- 11598261
TI  - Best cases from the AFIP. Hydatid cyst of the kidney: radiologic-pathologic
      correlation.

PMID- 11598262
TI  - Imaging of groin masses: inguinal anatomy and pathologic conditions revisited.
AB  - The groin region is subdivided into two distinct anatomic areas: the inguinal
      canal and the femoral triangle. A series of cross-sectional imaging cases
      illustrate that a good understanding of the local anatomic characteristics of the
      groin allows confident characterization of groin pathologic conditions. Such
      conditions can be classified into five major groups: congenital abnormalities,
      noncongenital hernias, vascular conditions, infectious or inflammatory processes,
      and neoplasms. Congenital entities include hernias, cysts, undescended testis,
      and retractile testes. Ultrasound (US) is useful in depicting these conditions.
      In the second group, noncongenital hernias, US allows visualization of bowel
      loops in peristalsis within the hernia. Herniography, computed tomography (CT),
      and magnetic resonance (MR) imaging are also helpful in diagnosis. Among vascular
      conditions, false aneurysms may be detected from the turbulent flow through the
      tract at Doppler US. The characteristic venous flow of varicoceles is best
      diagnosed with US during the Valsalva maneuver. Infectious or inflammatory
      conditions include, among others, hematomas, which appear hyperattenuating at CT
      and have variable appearances, depending on the age of the blood products, at MR
      imaging. The origins of neoplasms may be assessed at CT and MR imaging, although
      appearances of solid tumors are relatively nonspecific.

PMID- 11598263
TI  - Benign intratesticular cystic lesions: US features.
AB  - Benign intratesticular lesions are rare, but recognition is important to avoid
      unnecessary surgical intervention. The ultrasonographic (US) features that help
      differentiate benign from malignant intratesticular lesions are emphasized by the
      authors. Benign lesions include intratesticular simple cysts, tubular ectasia,
      epidermoid cyst, tunica albuginea cyst, intratesticular varicocele, abscess, and
      hemorrhage (infarction). US features of cystic malignant neoplasms that help in
      differentiation of them from benign cystic lesions are also presented. The US
      appearance of epidermoid cysts varies with the maturation, compactness, and
      quantity of keratin present. Of the cystic malignant testicular tumors, which can
      occur anywhere in testicular parenchyma, teratomas are the most frequent to
      manifest as cystic masses. An abnormal rind of parenchyma with increased
      echogenicity usually surrounds these lesions. An intratesticular spermatocele
      communicates with the seminiferous tubules, whereas simple ectasia of the rete
      testis does not do so directly. These cysts contain spermatozoa and can be
      septate. The US findings of intratesticular varicocele are similar to those of
      extratesticular varicocele and include multiple anechoic, serpiginous, tubular
      structures of varying sizes. Improvements in gray-scale and Doppler US technology
      allow subtle distinctions between benign and malignant testicular lesions that
      were not possible a decade earlier.

PMID- 11598264
TI  - MR imaging of the penis.
AB  - The signal intensity of the corpora cavernosa of the penis at magnetic resonance
      (MR) imaging may vary from that of the corpus spongiosum; this difference is
      dependent on the rate of blood flow within the cavernous spaces that constitute
      the corporal bodies. Also visible at MR imaging are the layers of fibrous tissue
      that envelop the corporal bodies, the deep arteries and veins, subcutaneous
      connective tissue, tunica dartos, epidermis, and urethra. While the iliac,
      pudendal, perineal, and common penile arteries can be evaluated with three
      dimensional MR angiography, the smaller end arteries of the penis have not yet
      been reliably demonstrated. MR imaging may be used to detect and stage penile and
      urethral cancers, identify and characterize benign penile masses, evaluate
      arteriogenic impotence, identify penile fractures, evaluate penile prostheses,
      localize periurethral abscesses, and identify plaques of Peyronie disease. With
      its direct multiplanar imaging capabilities, superb soft-tissue contrast, and
      excellent spatial resolution, high-field surface coil MR imaging can show the
      soft-tissue and vascular anatomy of the penis, as well as the appearance of many
      penile diseases.

PMID- 11598266
TI  - Requirement of heterochromatin for cohesion at centromeres.
AB  - Centromeres are heterochromatic in many organisms, but the mitotic function of
      this silent chromatin remains unknown. During cell division, newly replicated
      sister chromatids must cohere until anaphase when Scc1/Rad21-mediated cohesion is
      destroyed. In metazoans, chromosome arm cohesins dissociate during prophase,
      leaving centromeres as the only linkage before anaphase. It is not known what
      distinguishes centromere cohesion from arm cohesion. Fission yeast Swi6 (a
      Heterochromatin protein 1 counterpart) is a component of silent heterochromatin.
      Here we show that this heterochromatin is specifically required for cohesion
      between sister centromeres. Swi6 is required for association of Rad21-cohesin
      with centromeres but not along chromosome arms and, thus, acts to distinguish
      centromere from arm cohesion. Therefore, one function of centromeric
      heterochromatin is to attract cohesin, thereby ensuring sister centromere
      cohesion and proper chromosome segregation.

PMID- 11598267
TI  - A phosphatase associated with metastasis of colorectal cancer.
AB  - To gain insights into the molecular basis for metastasis, we compared the global
      gene expression profile of metastatic colorectal cancer with that of primary
      cancers, benign colorectal tumors, and normal colorectal epithelium. Among the
      genes identified, the PRL-3 protein tyrosine phosphatase gene was of particular
      interest. It was expressed at high levels in each of 18 cancer metastases studied
      but at lower levels in nonmetastatic tumors and normal colorectal epithelium. In
      3 of 12 metastases examined, multiple copies of the PRL-3 gene were found within
      a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3
      gene is important for colorectal cancer metastasis and provide a new therapeutic
      target for these intractable lesions.

PMID- 11598269
TI  - Inverse modeling of atmospheric carbon dioxide fluxes.

PMID- 11598268
TI  - A conserved family of prolyl-4-hydroxylases that modify HIF.
AB  - Mammalian cells respond to changes in oxygen availability through a conserved
      pathway that is regulated by the hypoxia-inducible factor (HIF). The alpha
      subunit of HIF is targeted for degradation under normoxic conditions by a
      ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF.
      We identified a conserved family of HIF prolyl hydoxylase (HPH) enzymes that
      appear to be responsible for this posttranslational modification. In cultured
      mammalian cells, inappropriate accumulation of HIF caused by forced expression of
      the HIF-1alpha subunit under normoxic conditions was attenuated by coexpression
      of HPH. Suppression of HPH in cultured Drosophila melanogaster cells by RNA
      interference resulted in elevated expression of a hypoxia-inducible gene (LDH,
      encoding lactate dehydrogenase) under normoxic conditions. These findings
      indicate that HPH is an essential component of the pathway through which cells
      sense oxygen.

PMID- 11598270
TI  - The state of the profession.

PMID- 11598271
TI  - Terrorism. Massive DNA identification effort gets under way.

PMID- 11598272
TI  - The Soviet legacy. Hoping software will help keep the peace.

PMID- 11598273
TI  - Biomedical research. First house vote good for NIH budget.

PMID- 11598274
TI  - Cancer research. New insights into metastasis.

PMID- 11598275
TI  - Epidemiology. HIV gains foothold in key Asian groups.

PMID- 11598276
TI  - Magnetoreception. Animal magnetism guides migration.

PMID- 11598277
TI  - Agricultural research. Tornado rips apart Maryland center.

PMID- 11598278
TI  - Scientific prizes. Researchers accept not-so-Nobel awards.

PMID- 11598279
TI  - Geoscience. From Earth's core to African oil.

PMID- 11598280
TI  - Nobel century. At 100, Alfred Nobel's legacy retains its luster.

PMID- 11598282
TI  - Nobel century. Nobel nuggets.

PMID- 11598281
TI  - Nobel century. Some Nobel milestones.

PMID- 11598283
TI  - Nobel century. Prizewinners, no--but not losers.

PMID- 11598284
TI  - Nobel century. For winners, a new life of opportunity--and perils.

PMID- 11598285
TI  - Oceans. Dis-crediting ocean fertilization.

PMID- 11598286
TI  - Geophysics. Peeling back the layers in Earth's mantle.

PMID- 11598287
TI  - Physics Quantum criticality in a clean metal.

PMID- 11598288
TI  - Structure. An anthropomorphic integrin.

PMID- 11598289
TI  - Signal transduction. Calcium channels--link locally, act globally.

PMID- 11598290
TI  - Carbon cycle. Potential impacts of CO2 injection on deep-sea biota.

PMID- 11598291
TI  - Phenotypic plasticity in the interactions and evolution of species.
AB  - When individuals of two species interact, they can adjust their phenotypes in
      response to their respective partner, be they antagonists or mutualists. The
      reciprocal phenotypic change between individuals of interacting species can
      reflect an evolutionary response to spatial and temporal variation in species
      interactions and ecologically result in the structuring of food chains. The
      evolution of adaptive phenotypic plasticity has led to the success of organisms
      in novel habitats, and potentially contributes to genetic differentiation and
      speciation. Taken together, phenotypic responses in species interactions
      represent modifications that can lead to reciprocal change in ecological time,
      altered community patterns, and expanded evolutionary potential of species.

PMID- 11598292
TI  - Magnetic field-tuned quantum criticality in the metallic ruthenate Sr3Ru2O7.
AB  - The concept of quantum criticality is proving to be central to attempts to
      understand the physics of strongly correlated electrons. Here, we argue that
      observations on the itinerant metamagnet Sr3Ru2O7 represent good evidence for a
      new class of quantum critical point, arising when the critical end point
      terminating a line of first-order transitions is depressed toward zero
      temperature. This is of interest both in its own right and because of the
      convenience of having a quantum critical point for which the tuning parameter is
      the magnetic field. The relationship between the resultant critical fluctuations
      and novel behavior very near the critical field is discussed.

PMID- 11598293
TI  - Signaling to the nucleus by an L-type calcium channel-calmodulin complex through
      the MAP kinase pathway.
AB  - Increases in the intracellular concentration of calcium ([Ca2+]i) activate
      various signaling pathways that lead to the expression of genes that are
      essential for dendritic development, neuronal survival, and synaptic plasticity.
      The mode of Ca2+ entry into a neuron plays a key role in determining which
      signaling pathways are activated and thus specifies the cellular response to
      Ca2+. Ca2+ influx through L-type voltage-activated channels (LTCs) is
      particularly effective at activating transcription factors such as CREB and MEF
      2. We developed a functional knock-in technique to investigate the features of
      LTCs that specifically couple them to the signaling pathways that regulate gene
      expression. We found that an isoleucine-glutamine ("IQ") motif in the carboxyl
      terminus of the LTC that binds Ca2+-calmodulin (CaM) is critical for conveying
      the Ca2+ signal to the nucleus. Ca2+-CaM binding to the LTC was necessary for
      activation of the Ras/mitogen-activated protein kinase (MAPK) pathway, which
      conveys local Ca2+ signals from the mouth of the LTC to the nucleus. CaM
      functions as a local Ca2+ sensor at the mouth of the LTC that activates the MAPK
      pathway and leads to the stimulation of genes that are essential for neuronal
      survival and plasticity.

PMID- 11598294
TI  - Oxygen isotopes and the moon-forming giant impact.
AB  - We have determined the abundances of 16O, 17O, and 18O in 31 lunar samples from
      Apollo missions 11, 12, 15, 16, and 17 using a high-precision laser fluorination
      technique. All oxygen isotope compositions plot within +/-0.016 per mil (2
      standard deviations) on a single mass-dependent fractionation line that is
      identical to the terrestrial fractionation line within uncertainties. This
      observation is consistent with the Giant Impact model, provided that the proto
      Earth and the smaller impactor planet (named Theia) formed from an identical mix
      of components. The similarity between the proto-Earth and Theia is consistent
      with formation at about the same heliocentric distance. The three oxygen isotopes
      (delta17O) provide no evidence that isotopic heterogeneity on the Moon was
      created by lunar impacts.

PMID- 11598295
TI  - Beryllium-10 from the Sun.
AB  - Beryllium-10 (10Be) in excess of that expected from in situ cosmic ray spallation
      reactions is present in lunar surface soil 78481; its presence was revealed with
      a sequential leaching technique. This excess 10Be, representing only 0.7 to 1.1%
      of the total 10Be inventory, is associated with surface layers (<1 micrometer) of
      the mineral grains composing 78481. This excess 10Be and its association with
      surficial layers corresponds to (1.9 +/- 0.8) x 10(8) atoms per square
      centimeter, requiring a 10Be implantation rate of (2.9 +/- 1.2) x 10(-6) atoms
      per square centimeter per second on the surface of the Moon. The most likely site
      for the production of this excess (10)Be is the Sun's atmosphere. The 10Be is
      entrained into the solar wind and transported to the lunar surface.

PMID- 11598296
TI  - Seismic observations of splitting of the mid-transition zone discontinuity in
      Earth's mantle.
AB  - The transition zone of Earth's mantle is delineated by globally observed
      discontinuities in seismic properties at depths of about 410 and 660 kilometers.
      Here, we investigate the detailed structure between 410 and 660 kilometers depth,
      by making use of regional stacks of precursors to the SS phase. The previously
      observed discontinuity at about 520 kilometers depth is confirmed in many
      regions, but is found to be absent in others. There are a number of regions in
      which we find two discontinuities at about 500 and 560 kilometers depth, an
      effect which can be interpreted as a "splitting" of the 520 kilometer
      discontinuity. These observations provide seismic constraints on the sharpness
      and observability of mineralogical phase transitions in the mantle transition
      zone.

PMID- 11598297
TI  - An ossified Meckel's cartilage in two Cretaceous mammals and origin of the
      mammalian middle ear.
AB  - An ossified Meckel's cartilage has been recovered from two early Cretaceous
      mammals from China. This element is similar to Meckel's cartilage in prenatal and
      some postnatal extant mammals and indicates the relationship of Meckel's
      cartilage with the middle ear in early mammals. The evidence shows that brain
      expansion may not be the initial factor that caused the separation of postdentary
      bones from the dentary as middle ear ossicles during mammalian evolution. The
      failure of the dentary to seize reduced postdentary elements during ontogeny of
      early mammals is postulated as an alternative mechanism for the separation.
      Modifications of both feeding and hearing apparatuses in early mammals may have
      led to the development of the definitive mammalian middle ear.

PMID- 11598298
TI  - Regional magnetic fields as navigational markers for sea turtles.
AB  - Young loggerhead sea turtles (Caretta caretta) from eastern Florida undertake a
      transoceanic migration in which they gradually circle the north Atlantic Ocean
      before returning to the North American coast. Here we report that hatchling
      loggerheads, when exposed to magnetic fields replicating those found in three
      widely separated oceanic regions, responded by swimming in directions that would,
      in each case, help keep turtles within the currents of the North Atlantic gyre
      and facilitate movement along the migratory pathway. These results imply that
      young loggerheads have a guidance system in which regional magnetic fields
      function as navigational markers and elicit changes in swimming direction at
      crucial geographic boundaries.

PMID- 11598299
TI  - Neuroanatomy of magnetoreception: the superior colliculus involved in magnetic
      orientation in a mammal.
AB  - The neural substrate subserving magnetic orientation is largely unknown in
      vertebrates and unstudied in mammals. We combined a behavioral test for magnetic
      compass orientation in mole rats and immunocytochemical visualization of the
      transcription factor c-Fos as a marker of neuronal activity. We found that the
      superior colliculus of the Zambian mole rat (Cryptomys anselli) contains neurons
      that are responsive to magnetic stimuli. These neurons are directionally
      selective and organized within a discrete sublayer. Our results constitute
      evidence for the involvement of a specific mammalian brain structure in
      magnetoreception.

PMID- 11598300
TI  - Observation of covalent intermediates in an enzyme mechanism at atomic
      resolution.
AB  - In classical enzymology, intermediates and transition states in a catalytic
      mechanism are usually inferred from a series of biochemical experiments. Here, we
      derive an enzyme mechanism from true atomic-resolution x-ray structures of
      reaction intermediates. Two ultra-high resolution structures of wild-type and
      mutant d-2-deoxyribose-5-phosphate (DRP) aldolase complexes with DRP at 1.05 and
      1.10 angstroms unambiguously identify the postulated covalent carbinolamine and
      Schiff base intermediates in the aldolase mechanism. In combination with site
      directed mutagenesis and (1)H nuclear magnetic resonance, we can now propose how
      the heretofore elusive C-2 proton abstraction step and the overall stereochemical
      course are accomplished. A proton relay system appears to activate a conserved
      active-site water that functions as the critical mediator for proton transfer.

PMID- 11598302
TI  - A small-molecule modulator of poly-alpha 2,8-sialic acid expression on cultured
      neurons and tumor cells.
AB  - Poly-alpha2,8-sialic acid (PSA) has been implicated in numerous normal and
      pathological processes, including development, neuronal plasticity, and tumor
      metastasis. We report that cell surface PSA expression can be reversibly
      inhibited by a small molecule, N-butanoylmannosamine (ManBut). Inhibition occurs
      through a metabolic mechanism in which ManBut is converted to unnatural sialic
      acid derivatives that effectively act as chain terminators during cellular PSA
      biosynthesis. N-Propanoylmannosamine (ManProp), which differs from ManBut by a
      single methylene group, did not inhibit PSA biosynthesis. Modulation of PSA
      expression by chemical means has a role complementary to genetic and biochemical
      approaches in the study of complex PSA-mediated events.

PMID- 11598301
TI  - Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v
      Akt at the plasma membrane.
AB  - The PKB (protein kinase B, also called Akt) family of protein kinases plays a key
      role in insulin signaling, cellular survival, and transformation. PKB is
      activated by phosphorylation on residues threonine 308, by the protein kinase
      PDK1, and Serine 473, by a putative serine 473 kinase. Several protein binding
      partners for PKB have been identified. Here, we describe a protein partner for
      PKBalpha termed CTMP, or carboxyl-terminal modulator protein, that binds
      specifically to the carboxyl-terminal regulatory domain of PKBalpha at the plasma
      membrane. Binding of CTMP reduces the activity of PKBalpha by inhibiting
      phosphorylation on serine 473 and threonine 308. Moreover, CTMP expression
      reverts the phenotype of v-Akt-transformed cells examined under a number of
      criteria including cell morphology, growth rate, and in vivo tumorigenesis. These
      findings identify CTMP as a negative regulatory component of the pathway
      controlling PKB activity.

PMID- 11598303
TI  - The bottom line for U.S. life scientists.

PMID- 11598304
TI  - General contentment masks gender gap in first AAAS salary and job survey.

PMID- 11598305
TI  - Miniprofiles.

PMID- 11598306
TI  - Normal optic nerve head topography in the early stages of dementia of the
      Alzheimer type.
AB  - In view of the existing controversy as to whether or not the optic nerve head
      (ONH) is altered in Alzheimer disease, we used modern imaging technology to
      evaluate the ONH structure in individuals with dementia of the Alzheimer type
      (DAT). Real-time topographical images of the ONH were obtained with a Heidelberg
      retina tomograph from individuals in the early stages of DAT and age-matched
      controls. The various ONH parameters examined in this study did not differ
      significantly between DAT and age-matched subjects. These results suggest that
      the deficits in visual function that are known to occur in DAT are not related to
      ONH structural anomalies, at least in the earlier stages of the disease.

PMID- 11598307
TI  - The Swedish APP670/671 Alzheimer's disease mutation: the first evidence for
      strikingly increased oxidative injury in the temporal inferior cortex.
AB  - To evaluate the level of oxidative stress (OS) in familial Alzheimer's disease
      (FAD), we analysed four cerebrocortical areas from patients with Swedish FAD
      bearing the APP670/671 mutation. The temporal inferior cortex (TIC) from Swedish
      FAD patients revealed a striking 2- to 3-fold increase in diene conjugates, lipid
      peroxides and protein carbonyls, compared to sporadic Alzheimer's disease (AD).
      Compared with TIC from sporadic AD patients, the mutation carriers showed a
      markedly decreased activity of catalase (CAT) in the same area, and the same
      trend was found for another antioxidant enzyme, superoxide dismutase. These
      results are consistent with the deep oxidative injury of TIC in Swedish FAD. In
      the frontal inferior cortex (FIC), sensory postcentral cortex (SPCC) and
      occipital primary cortex (OPC) from Swedish FAD, the parameters of oxidative
      injury tended to be higher than in sporadic AD. Only the increase in the levels
      of lipid hydroperoxides in SPCC and of protein carbonyls in OPC was significant.
      Compared to sporadic AD, Swedish FAD showed a significant increase in GSSG levels
      and the GSSG/2GSH ratio in the FIC, SPCC and OPC. A significantly decreased
      activity of CAT was detectable for the SPCC and OPC in Swedish FAD. Increased OS
      might play a crucial role in the rapid progression of Swedish FAD from the
      associative temporal cortex to the primary cerebrocortical areas.

PMID- 11598308
TI  - Is there a typical pattern of brain SPECT imaging in Alzheimer's disease?
AB  - The identification of new nosological forms such as Lewy body disease (LBD)
      requires a re-evaluation of the patterns observed in brain functional imaging in
      the various forms of dementia. We studied 60 demented patients, divided into
      three groups and fulfilling the clinical criteria for Alzheimer's disease (AD),
      LBD and frontotemporal dementia (FTD), using Tc-HMPAO and a brain-dedicated SPECT
      system. After normalisation we applied a cut-off at two levels according to
      previously established criteria. We reaffirmed the already established data
      concerning FTD (mainly a bilateral frontal decrease) and for LBD (a severe
      diffuse decrease in the frontal regions and also in the posterior association
      cortex). In contrast, the decrease in AD was strictly limited to the parieto
      occipital cortex, irrespective of the severity of the cognitive decline. We
      hypothesise that the major simplification concerning the pattern observed in AD
      can be explained by the fact that patients suffering from LBD have previously
      been included in the groups of AD patients.

PMID- 11598309
TI  - Primary degenerative mild cognitive impairment: study population, clinical, brain
      imaging and biochemical findings.
AB  - Mild cognitive impairment (MCI) is a heterogeneous clinical syndrome for which no
      international diagnostic criteria have yet been established. Longitudinal studies
      have shown that many individuals who later develop dementia pass through a stage
      of MCI. We are following up 36 individuals who were initially diagnosed as having
      the memory-impaired primary degenerative type of MCI and therefore are at high
      risk of developing Alzheimer's disease. Clinical, neuropsychological, brain
      imaging and CSF biochemical markers were examined. Findings were remarkably
      heterogeneous even in this highly selected group of patients. This suggests that
      MCI is aetiologically not uniform.

PMID- 11598310
TI  - Genetic analysis in patients with familial and sporadic frontotemporal dementia:
      two tau mutations in only familial cases and no association with apolipoprotein
      epsilon4.
AB  - We screened for tau gene mutations among 24 Japanese (6 familial and 18 sporadic
      cases) and 4 Polish patients with frontotemporal dementia (FTD) using PCR-SSCP
      analysis followed by DNA sequencing. We identified 2 missense mutations in exon
      10: N279K and P301L in 2 Japanese patients with familial FTD. Additionally 3 DNA
      polymorphisms: 2 known (3' exon 3 + 9, A --> G and exon 7, codon 176, G --> A)
      and 1 new (exon 8, codon 185, T --> C) were identified in 1 Polish patient. Tau
      mutations were not found in subjects with a negative family history suggesting
      that tau mutations do not account for most sporadic cases of FTD. We also found
      no association of apolipoprotein E4 allele with FTD.

PMID- 11598311
TI  - Frontotemporal lobar degeneration: a study in Japan.
AB  - Frontotemporal lobar degeneration is the most common form of cortical dementia
      occurring in the presenium after Alzheimer's disease. We analyzed two types of
      frontotemporal dementia (FTD) and semantic dementia (SD) selected from a
      consecutive series of outpatients based on neuropsychological symptoms,
      psychiatric symptoms and abnormal behavior. In our series of 134 patients with
      primary degenerative dementia, there were 16 cases of FTD and 6 cases of SD.
      Patients with subgroups of FTD and patients with SD were distinguishable only by
      the presence of aphasia in the latter group. They were not distinguishable from
      one another by other neuropsychological examinations, behavioral abnormalities or
      psychiatric symptoms assessed with the Neuropsychiatric Inventory.

PMID- 11598312
TI  - Repeated pain assessment in Alzheimer's disease.
AB  - In previous studies, patients with probable Alzheimer's disease (AD) have
      indicated that they experienced less pain intensity and affect from their painful
      conditions than nondemented elderly persons. However, in those studies, pain
      assessment occurred only once. Therefore, it may be possible that pain which had
      occurred, for example, a day earlier, could have been forgotten. Therefore, in
      the present study, AD patients' pain was assessed daily, i.e. once a day and even
      three times a day, during a longer period. The results parallel those of earlier
      studies, i.e. compared to elderly persons without dementia, AD patients appear to
      perceive less pain intensity and pain affect. These findings support the
      hypothesis that AD is characterized by an alteration in pain experience.

PMID- 11598313
TI  - Treatment of Alzheimer's disease with clioquinol.
AB  - As heavy metal ions may be implicated in the formation of senile plaques in
      Alzheimer-afflicted brains, treatment with clioquinol was tested in 20 patients
      with Alzheimer's disease. Clioquinol is a chelator that crosses the blood-brain
      barrier and has greater affinity for zinc and copper ions than for calcium and
      magnesium ions. Treatment was given for 21 days at doses of 20 mg/day to 10
      patients and 80 mg/day to another 10 patients. The study was blind to the dosages
      but included no controls. Cerebrospinal fluid (CSF) investigations revealed a
      significant increase at day 7 and a decrease at day 21 in Tau protein and growth
      associated protein (GAP43). These proteins are increased in Alzheimer's disease
      and considered as rather stable markers. The initial increase may indicate a
      temporary cytotoxicity to the brain and/or an increased release into the CSF from
      stores in the tissue, possibly from senile plaques where the proteins are
      accumulated. The levels of CSF-Tau protein correlated positively and
      significantly with the serum levels of copper and also with the serum copper/zinc
      ratio. Clinical ratings showed slight improvement after 3 weeks treatment with
      clioquinol in this open study.

PMID- 11598314
TI  - Perinatal Brain Injury. Proceedings and abstracts of the 2nd Hershey Conference
      on Developmental Cerebral Blood Flow and Metabolism. Hershey, Pennsylvania, USA.
      June 8-11, 2000.

PMID- 11598315
TI  - Pathophysiology of perinatal brain damage.
AB  - Brain damage in the premature or full-term fetus or newborn infant encompasses
      multiple patterns of injury, many considered to be anomalous in origin. However,
      there is increasing evidence that such congenital lesions arise as a consequence
      of hypoxia or ischemia (reperfusion failure). Animal models have been helpful in
      elucidating the underlying cellular and molecular mechanisms responsible for
      perinatal brain damage. Ultimately, neuroprotective strategies will prevent or
      minimize the occurrence of these lesions and their consequent functional
      deficiencies.

PMID- 11598316
TI  - The premature fetus: not as defenseless as we thought, but still paradoxically
      vulnerable?
AB  - Traditionally, it has been believed that the cardiovascular and hormonal
      responses to asphyxia in preterm fetuses are immature, and this immaturity
      contributes to their apparent vulnerability to neural injury. However, these data
      were derived from studies using relatively mild insults, which did not allow for
      the greater cardiac glycogen reserves and anaerobic capacity of the brain near
      midgestation. Here, we review the maturation of the cardiovascular and
      cerebrovascular and cerebral responses to asphyxia in experimental animals and
      how these relate to the apparent vulnerability of the human premature brain. Most
      such investigations have been performed in the chronically instrumental fetal
      sheep. Recent studies have demonstrated that the premature fetus has highly
      adaptive and relatively mature responses to asphyxia, and that in absolute terms
      the preterm brain is very resistant to asphyxial injury. These data suggest that
      the premature fetus is able to survive much more prolonged periods of asphyxia
      than the near-term fetus, but that, paradoxically, such survival is associated
      with exposure to prolonged periods of hypotension and hypoperfusion and
      consequently greater risk of severe neural damage.

PMID- 11598317
TI  - Delayed cerebral atrophy following moderate hypoxia-ischemia in the immature rat.
AB  - Hypoxia-ischemia (H/I) damages cells in the immature brain and interferes with
      subsequent brain development; the extent of the damage has been related to the
      severity, or duration, of the initial insult. This study examined the effects of
      both severe and moderate duration of H/I on the evolution of damage through 8
      weeks of recovery. Seven-day-old rat pups were subjected to either 75 min or 2 h
      of 8% oxygen following a unilateral carotid artery ligation. Evaluation of brain
      damage included morphometric analysis of hemispheric diameter at 2, 4, and 8
      weeks of recovery, and hematoxylin and eosin for evaluation of pathology at 8
      weeks. Two hours of H/I produced severe infarction in the ipsilateral hemisphere
      in the majority of the survivors, apparent by 2 weeks of recovery with no change
      at 4 or 8 weeks. In marked contrast, 75 min of H/I produced no significant damage
      during the initial 2 weeks of recovery but resulted in progressive cerebral
      atrophy with delayed infarction such that the extent of damage at 8 weeks was not
      different from the 2-hour group. Thus, even a mild-moderate ischemic insult to
      the perinatal brain establishes a vulnerable region which ultimately dies without
      intervention.

PMID- 11598318
TI  - Neurodegeneration in the thalamus following neonatal hypoxia-ischemia is
      programmed cell death.
AB  - We studied neuronal cell body, axonal, and terminal degeneration in brains from 7
      day-old rat pups recovered for 0, 1.5, 3, 6, 24, 48, 72 h, and 6 days following
      hypoxia-ischemia and identified proteins involved in the delayed
      neurodegeneration in the thalamus. We found that injury is biphasic with initial
      necrosis in the ipsilateral forebrain by 3 h following hypoxia-ischemia, in
      contrast to more delayed and apoptotic-like injury in the ventral-basal thalamus,
      brainstem, and other remote non-forebrain regions. Prior to the appearance of
      large numbers of apoptotic profiles in the ventral-basal thalamus, expression of
      Fas death receptor protein, activated forms of caspase 8 and caspase 3, and pro
      apoptotic Bcl-2 proteins are increased. This manuscript combines our data on
      hypoxic-ischemic injury in the developing brain and presents evidence for at
      least two forms of neurodegeneration, namely, acute necrosis in the forebrain and
      delayed neurodegeneration in the thalamus, which is death-receptor-mediated
      programmed cell death.

PMID- 11598319
TI  - Cerebral hypoxia-ischemia in immature rats: involvement of mitochondrial
      permeability transition?
AB  - The aim of this study was to evaluate the involvement of mitochondrial membrane
      permeability transition (MPT) after hypoxia-ischemia (HI) in 7-day-old rats.
      [14C]2-deoxyglucose (DOG) was administered to controls, and at various time
      points after HI. MPT in the cerebral cortex was measured as entrapment of DOG-6-P
      in mitochondria. Another group of rats was treated with the MPT inhibitor
      cyclosporin A (CsA; 10-50 mg/kg i.p.) or vehicle before and after HI, and the
      effect on brain injury and mitochondrial respiration was evaluated. A significant
      increase in DOG-6-P entrapment in mitochondria indicated that MPT occurred in two
      phases: a primary MPT after 0-1.5 h and a secondary MPT after 6.5-8 h of
      reperfusion. However, CsA did not affect brain injury or mitochondrial
      respiration. The data suggest that MPT occurred after HI but does not provide
      evidence for its involvement in the development of injury.

PMID- 11598320
TI  - Oxidant mechanisms in neonatal hypoxia-ischemia.
AB  - The neonatal brain appears to be selectively vulnerable to oxidative stress.
      Several potential mechanisms associated with altered reactive oxygen species
      metabolism would explain the increased susceptibility. They include increased
      accumulation of hydrogen peroxide with subsequent neurotoxicity. This enhanced
      neurotoxicity from H2O2 accumulation may be related to inadequate scavenging
      abilities of the immature nervous system, such as lower glutathione peroxidase
      activity. Contributing to the immaturity of the scavenging enzymes is the
      inability of the developing nervous system to maintain glutathione stores. The
      immature nervous system is rich in iron, and has more free iron than the mature
      nervous system. As H2O2 accumulates because of these improper defense mechanisms,
      it is exposed to this free iron. This exposure results in the generation of OH
      radical (Fenton reaction), a more potent free radical that can cause severe
      damage. The rapid conversion of H2O2 to OH in the setting of free iron sets up
      the immature nervous system for increased cytotoxicity. Understanding the
      molecular mechanisms of oxidative stress will lead to better therapies for
      neonatal hypoxia-ischemia.

PMID- 11598321
TI  - Perinatal hypoxia-ischemia induces apoptotic and excitotoxic death of
      periventricular white matter oligodendrocyte progenitors.
AB  - Hypoxia-ischemia (HI) is a leading cause of white matter damage, a major
      contributor to cerebral palsy in premature infants. Preferential white matter
      damage is believed to result from vulnerability of the immature oligodendrocyte
      (the pro-OL) to factors elevated during ischemic damage, such as oxygen free
      radicals and glutamate. In order to determine whether pro-OLs undergo apoptotic
      death after HI, we analyzed periventricular white matter OLs in P7 rats 4, 12 and
      24 h after HI to analyze the time course and mode of cell death. DNA
      fragmentation was seen at 12 and 24 h of recovery after HI, representing a 17
      fold increase over control. In addition, caspase-3 activation was found in NG2+
      pro-OLs at 12 h. Electron-microscopic analysis of cell death in the white matter
      revealed a transition from early necrotic deaths to hybrid cell deaths to
      classical apoptosis between 4 and 24 h of recovery from HI. The delayed time
      course of apoptosis in pro-OLs supports the feasibility of interventions to
      improve clinical outcomes for newborns surviving birth asphyxia.

PMID- 11598322
TI  - White matter injury in the preterm neonate: the role of perfusion.
AB  - The preterm infant is at special risk of white matter injury. It was hypothesized
      long ago that ischemia is the principal etiology. The commonly used experimental
      animals for perinatal brain injury research may differ importantly from humans as
      regards the white matter. Therefore, evidence from human neonates that the white
      matter is selectively exposed to ischemia is relevant. Blood flow to the white
      matter appears to be particularly low in the premature human infant, with only
      17% of flow to the gray matter. Furthermore, the blood flow to the white matter
      appears to be selectively reduced when blood pressure is low. There are important
      methodological limitations to all the studies reviewed; whereas the hypothesis
      has not had strong support, it has not been refuted. It appears wise to consider
      ischemia to the white matter a real threat in sick preterm infants.

PMID- 11598323
TI  - Human perinatal asphyxia: correlation of neonatal cytokines with MRI and outcome.
AB  - Clinical studies of the preterm neonate and animal models of asphyxial brain
      injury both support a role for proinflammatory cytokines in central nervous
      system (CNS) injury. There are fewer studies of perinatal CNS injury in the full
      term neonate. We have performed a prospective cohort study of full-term infants
      with perinatal asphyxia. Using archived neonatal blood samples, we have analyzed
      the serum levels of several proinflammatory cytokines. Preliminary results
      demonstrate an increase in IL-1, IL-6, and TNF-alpha in those children who are
      deceased at 1 year or who have a diagnosis of cerebral palsy versus those with
      normal neuromotor outcome. Further analysis will include correlations of cytokine
      levels with injury on MRI spectroscopy, with neonatal clinical markers of
      encephalopathy, and with later neurodevelopmental outcome.

PMID- 11598324
TI  - Age-dependent consequences of seizures and the development of temporal lobe
      epilepsy in the rat.
AB  - The age-related functional changes underlying epileptogenesis remain to be
      clarified. In the present study, we explored the correlation between metabolic
      changes, neuronal damage and epileptogenesis during the acute, silent and chronic
      phases following status epilepticus (SE) induced by lithium-pilocarpine (Li-Pilo)
      in 10- (P10), 21-day-old (P21) and adult rats. Local cerebral metabolic rates for
      glucose (LCMRglcs) were measured by the [14C]2-deoxyglucose method during SE, the
      silent period and the interictal phase of the chronic period. Neurodegeneration
      was assessed by cresyl violet staining. During SE, LCMRglcs dramatically
      increased at all ages mainly in forebrain vulnerable regions. During the silent
      phase, in P21 and adult rats, metabolic decreases were recorded in damaged
      forebrain regions involved in the genesis and propagation of seizures 14 days
      after SE. At the end of the silent phase, P21 and adult rats exhibited metabolic
      increases in intact brainstem areas involved in the remote control of epilepsy.
      During the interictal phase of the chronic period, LCMRglcs decreased in damaged
      forebrain areas of adult and P21 rats that were not spontaneously epileptic,
      while LCMRglcs were similar to control levels in epileptic P21 rats. In P10 rats,
      there was no damage and no metabolic consequences at any time after SE. In
      conclusion, the process of epileptogenesis and its functional consequences differ
      in P21 and adult rats. The factors underlying these age-related differences
      remain to be explored.

PMID- 11598325
TI  - Effects of maturation on mechanisms of cGMP-induced cerebral vasodilatation.
AB  - In light of observations that cerebrovascular levels of cGMP vary during
      maturation, the present study examines the possibility that the mechanisms
      mediating cGMP-induced cerebral vasodilatation also change during maturation.
      Specifically, these experiments explore age-related changes in the ability of
      cGMP to both: (1) depress cytosolic calcium concentration, and (2) attenuate
      contractile protein calcium sensitivity in alpha-toxin and beta-escin
      permeabilized preparations as well as fura-2 loaded arteries. The present data
      demonstrate that: (1) cGMP attenuates cytosolic calcium concentration at lower
      concentrations than required to reduce myofilament calcium sensitivity; (2) both
      potassium-induced and 5HT-induced contractions were more sensitive to cGMP in
      fetal than adult arteries; (3) all potassium-induced increases in cytosolic
      calcium were resistant to the effects of cGMP, but those produced by 5HT were
      sensitive to attenuation by cGMP, and more so in fetal than in adult basilar
      arteries, and (4) cGMP attenuated both basal and agonist-enhanced myofilament
      calcium sensitivity. Overall, these data demonstrate that the mechanisms
      mediating the multiple vasoactive effects of cGMP are more potent in immature
      than in mature cerebral arteries and are heavily influenced by both the artery
      type and the method of contraction.

PMID- 11598326
TI  - Hypoxia/ischemia depletes the rat perinatal subventricular zone of
      oligodendrocyte progenitors and neural stem cells.
AB  - Cerebral hypoxia/ischemia of the newborn has a frequency of 4/1,000 births and
      remains a major cause of cerebral palsy, epilepsy, and mental retardation.
      Despite progress in understanding the pathogenesis of hypoxic-ischemic injury,
      the data are incomplete regarding the mechanisms leading to permanent brain
      injury. Here we tested the hypothesis that cerebral hypoxia/ischemia damages
      stem/progenitor cells in the subventricular zone (SVZ), resulting in a permanent
      depletion of oligodendrocytes. We used a widely accepted rat model and examined
      animals at recovery intervals ranging from 4 h to 3 weeks. Within hours after the
      hypoxic-ischemic insult 20% of the total cells were deleted from the SVZ. The
      residual damaged cells appeared necrotic. During 48 h of recovery deaths
      accumulated; however, these later deaths were predominantly apoptotic. Many
      apoptotic SVZ cells stained with a marker for immature oligodendrocytes. At 3
      weeks survival, the SVZ was smaller and markedly less cellular, and it contained
      less than 1/4 the normal complement of neural stem cells. The corresponding
      subcortical white matter was dysmyelinated, relatively devoid of oligodendrocytes
      and enriched in astrocytes. We conclude that neural stem cells and
      oligodendrocyte progenitors in the SVZ are vulnerable to hypoxia/ischemia.
      Consequently, the developmental production of oligodendrocytes is compromised and
      regeneration of damaged white matter oligodendrocytes does not occur resulting in
      failed regeneration of CNS myelin in periventricular loci. The resulting
      dysgenesis of the brain that occurs subsequent to perinatal hypoxic/ischemic
      injury may contribute to the cognitive and motor dysfunction that results from
      asphyxia of the newborn.

PMID- 11598327
TI  - Botulinum toxin type B: where do we stand?

PMID- 11598328
TI  - Relationship between leuko-araiosis and blood pressure variability in the
      elderly.
AB  - Although leuko-araiosis is a common finding on computed tomographic (CT) scans of
      the brain, its pathogenesis remains uncertain. To investigate the association
      between blood pressure (BP) disturbances and leuko-araiosis, we retrospectively
      reviewed CT scans and 24-hour ambulatory blood pressure monitorings of 79 elderly
      patients (57 women and 22 men; mean age: 83.3 +/- 6.4 years). Of the 79 patients,
      50 were demented (30 had Alzheimer's disease and 18 vascular dementia) and 29
      were not demented. The leuko-araiosis score (LA score) was determined by using
      Rezek's scale. To evaluate short-term variation of BP, we determined (1) the
      variability of systolic and diastolic BPs (SBP, DBP; within-subject standard
      deviation of all readings over a 24-hour period), (2) the coefficient of
      variability (variability of BP/mean BP) and (3) the maximal variation of BP
      (difference between the maximum and minimum 24-hour BPs). Higher LA scores were
      associated with higher SBPs in 24-hour, diurnal and nocturnal periods, higher
      maximal variation of SBP, greater variability of SBP during 24-hour, diurnal and
      nocturnal periods and greater coefficient of variability of SBP during sleep. Our
      study suggests that elevations and short-term variations of SBP may contribute to
      the pathogenesis of white matter lesions in elderly persons.

PMID- 11598329
TI  - Planum temporale: where spoken and written language meet.
AB  - Functional magnetic resonance imaging studies on spoken versus written language
      processing were performed in 20 right-handed normal volunteers on a high-field
      (3.0-tesla) system. The areas activated in common by both auditory (listening)
      and visual (reading) language comprehension paradigms were mapped onto the planum
      temporale (20/20), primary auditory region (2/20), superior temporal sulcus area
      (2/20) and planum parietale (3/20). The study indicates that the planum temporale
      represents a common traffic area for cortical processing which needs to access
      the system of language comprehension. The destruction of this area can result in
      comprehension deficits in both spoken and written language, i.e. a classical case
      of Wernicke's aphasia.

PMID- 11598330
TI  - Homonymous defect of macular vision in ischemic stroke.
AB  - It is generally believed that a homonymous defect of macular vision (HMV) is
      caused by a small lesion restricted to the occipital lobe tip and rarely results
      from ischemic stroke. The incidence of HMV was studied retrospectively in 54
      patients with infarction of the posterior cerebral artery territory who underwent
      Goldmann's visual field test. HMV was found in 6 patients (11%). In all of them,
      HMV was first dismissed due to a confrontation test of visual fields at the
      bedside and later detected by Goldmann's visual field test. All had a relatively
      large infarction extending from the occipital lobe tip to the posterior part of
      the calcarine cortex and/or the neighboring subcortical regions. Stroke-induced
      HMV can be caused by a large lesion involving the occipital pole and may not be
      so rare as generally considered.

PMID- 11598331
TI  - Dilated Virchow-Robin spaces in myotonic dystrophy: frequency, extent and
      significance.
AB  - To study the frequency, extent and significance of dilated Virchow-Robin spaces
      (VRSs) in dystrophia myotonica (DM), we evaluated the cranial magnetic resonance
      imaging (MRI) of 41 patients with the adult form of DM and 41 healthy controls.
      Dilated VRSs and white matter lesions (WMLs) were rated according to
      semiquantitative methods. Convexity VRSs were more frequent (68 vs. 34%; p <
      0.01) and severer (median scores: 4 vs. 0; p < 0.01) in DM patients than in
      controls, while lenticulostriate VRSs did not show significant differences in
      frequency (83 vs. 70%; p > 0.05) and severity (median scores: 4 vs. 3; p > 0.05).
      WMLs were more frequent (66 vs. 22%; p < 0.01) and severer (median scores: 5 vs.
      0; p < 0.01) in patients. Disease duration was negatively correlated with
      convexity VRSs and positively with lobar (centrum semiovale) WML scores. Dilated
      convexity VRSs might be one of the initial findings in cranial MRI of DM,
      preceding the appearance of lobar WMLs.

PMID- 11598332
TI  - An atypical neuropsychological profile of a Korsakoff syndrome patient throughout
      the follow-up.
AB  - The basis of amnesia in alcoholic Wernicke-Korsakoff syndrome (WKS) has been
      generally associated with diencephalic lesions and more specifically with lesions
      of the anterior thalamic nuclei. These brain structures are considered to be
      involved in encoding/consolidation processes of episodic memory. However, frontal
      lobe damage responsible for executive function deficits has also been documented.
      The present report details the nature and extent of amnesia in an alcoholic
      patients with WKS and which appears to be mainly due to frontal lobe (executive)
      deficits.

PMID- 11598333
TI  - Blood flow in the left atrial appendage and embolic stroke in nonvalvular atrial
      fibrillation.
AB  - It is unclear if low flow velocity in the left atrial appendage (LAA) is a
      predisposing factor to stroke in patients with nonvalvular atrial fibrillation
      (NVAF). We investigated flow velocity in the LAA in NVAF patients in relation to
      a past history of stroke and other potential embolic sources. We measured and
      analyzed peak flow velocities into (FV-in) and out of (FV-out) the LAA in a
      middle portion of the LAA in 35 NVAF patients by transesophageal echocardiography
      (TEE). We divided the NVAF patients into 3 groups: the Eaf group had a history of
      embolic stroke without any other potential embolic sources; the Emulti group had
      other potential embolic sources, and the control group had no embolic history. FV
      in and FV-out in the Eaf group (12.3 +/- 6.7 and 10.2 +/- 7.3 cm/s) were
      significantly lower than those in the control group (24.3 +/- 11.3 and 19.9 +/-
      8.8 cm/s; multicomparison Scheffe's test, p = 0.0123 and 0.0395, respectively).
      The Emulti group varied in those values from less than 5 to above 35. Low flow
      velocity in the LAA seems to be a predisposing factor for stroke in NVAF patients
      without any other sources of emboli.

PMID- 11598334
TI  - Lack of evidence for an association between two genetic polymorphisms in the
      tumor necrosis factor receptor 1 gene and multiple sclerosis in Ashkenazi Jews.
AB  - Multiple sclerosis (MS) is a multifactorial disease with a documented genetic
      component. Recent experimental models suggested a role for the tumor necrosis
      factor receptor 1 (TNFR1) in the pathogenesis of the disease. We compared the
      frequency of two polymorphisms from TNFR1, located in exon 1 and intron 6, in 94
      Jewish Ashkenazi MS patients and 83 healthy Ashkenazi controls. No significant
      differences were observed for both polymorphisms between the patients and the
      controls. These findings suggest that genetic variants in TNFR1 do not play a
      significant role in Ashkenazi Jews.

PMID- 11598335
TI  - Polyradiculomyelitis associated with clinically diagnosed tuberculous meningitis.

PMID- 11598336
TI  - Lafora body-like inclusions in a case of progressive myoclonic ataxia associated
      with coeliac disease.

PMID- 11598337
TI  - Neuroleptic malignant-like syndrome and acute hepatitis during tolcapone and
      clozapine medication.

PMID- 11598338
TI  - Spinal cavitous hemorrhagic infarction with abdominal aortic aneurysm.

PMID- 11598339
TI  - Isolated angiitis of the central nervous system: report of a patient with an
      unusually prolonged course.

PMID- 11598340
TI  - Cerebral vasculopathy showing moyamoya-like changes in a patient with CREST
      syndrome.

PMID- 11598341
TI  - Temporal lobe epilepsy following febrile seizures: unusually prolonged latent
      periods.

PMID- 11598342
TI  - MR findings in Balint's syndrome, following intrathecal methotrexate and
      cytarabine therapy in adult acute lymphoblastic leukemia.

PMID- 11598343
TI  - Successful treatment of Guillain-Barre syndrome with combined administration of
      interferon-beta-1a and intravenous immunoglobulin.

PMID- 11598345
TI  - Aims and methods. LUTS suggestive of BPH.
AB  - OBJECTIVE: Few epidemiological studies are available on Italian patients with
      lower urinary tract symptoms and their QoL. QUIBUS (QUality of life Investigated
      in BPH patients with Urinary Symptoms) is an observational longitudinal study
      aimed at evaluating symptoms and QoL in a large sample of Italian patients and
      investigating their correlation with demographic, social and clinical
      characteristics of BPH. PATIENTS AND METHODS: Patients with lower urinary tract
      symptoms and prostate enlargement suggestive of BPH (both old and new diagnosis)
      were enrolled between November 1998 and May 1999 in 31 Italian centers of
      urology. This longitudinal investigation consists of an enrollment visit, in
      which demographic, social and clinical aspects are recorded as baseline data, and
      a follow-up visit after 1 year of treatment freely assigned by the investigators.
      Symptoms and QoL are assessed by means of IPSS, ICS-BPH (at both visits) and SF
      36 (only at the follow-up visit) questionnaires. RESULTS: 1,033 patients were
      enrolled. The follow-up visit is still under evaluation. In this series of papers
      the baseline results are presented and discussed in terms of (i) medical
      management, (ii) life-style, (iii) symptoms, bothersomeness and QoL, (iv) sexual
      function of a large and representative sample of Italian patients and (v)
      uroflowmetry.

PMID- 11598346
TI  - Management of patients with LUTS suggestive of BPH.
AB  - The QUIBUS study offers some insights into the current diagnosis and treatment of
      LUTS suggestive of BPH in Italy. As diagnosis is concerned, uroflowmetry and PSA
      testing were performed in a high percentage of cases (64 and 89%, respectively).
      Both transrectal ultrasonography and prostate biopsy were more frequent for
      increasing values of PSA, this suggesting that are used as screening procedures
      for prostate cancer. However, transrectal ultrasonography was performed overall
      in a large proportion of patients (61%), representing a routine examination in
      some centers. As treatment is concerned, the majority of QUIBUS patients had
      undergone or were undergoing medical therapy. Alphalytics were the drugs most
      commonly prescribed by urologists while primary care physicians showed the
      attitude to prescribe more frequently finasteride. On the surgical side,
      transurethral prostatectomy and open surgery were the most commonly employed
      procedures, suggesting that little room is left at present to minimally invasive
      procedures in Italy.

PMID- 11598347
TI  - Life-style in patients with LUTS suggestive of BPH.
AB  - BACKGROUND: Owing to the existing controversy about the role of life-style in the
      pathogenesis of BPH, the possible associations of LUTS and prostate enlargement
      with alcohol intake, coffee consumption, smoking, physical activity, body mass
      index (BMI) and concomitant diseases were studied in the large series of patients
      of the QUIBUS study. RESULTS: Among concomitant diseases, essential hypertension
      was the most represented. However no apparent additive or synergistic influence
      on symptoms was recorded in this subset of the population. Coffee consumption was
      not associated with prostate volume or LUTS. Alcohol consumption was associated
      with urgency and intermittence and with an overall higher IPSS. No major
      influence on symptoms was found in smokers. Physical activity was associated with
      a lower frequency of incomplete bladder emptying, repeated urination,
      intermittence and urgency. The postulated existence of an association between BMI
      and BPH was not confirmed in this study. When a prediction of the IPSS scores was
      tempted by entering the life-style factors in a multiple regression model, they
      were able to explain at best 5% of the variance of the dependent variable.
      CONCLUSION: Life-style patterns bear a greater influence on individual symptoms
      than on total scores. This difference is sometimes high enough to recommend
      specific life-style measures to patients with LUTS and prostate enlargement.

PMID- 11598348
TI  - Symptoms, bothersomeness and quality of life in patients with LUTS suggestive of
      BPH.
AB  - The QUIBUS study is the largest investigation ever performed in Italy with an
      extensive use of the ICS-BPH questionnaire. The internal consistency of each of
      its three domains was high for ICS-Male (Cronbach's alpha = 0.83 and 0.89 for
      symptoms and bother, respectively) and lower for ICS-Sex (Cronbach's alpha = 0.63
      and 0.75, see a following paper of this issue) and ICS-QoL (Cronbach's alpha =
      0.53), as previously reported in the validation study of this tool. Voiding
      symptoms were more frequently reported, with reduced urinary stream, terminal
      dribble and incomplete bladder emptying as the most frequently represented. The
      first storage symptom in the ranking by frequency was 'rush to toilet' (70% of
      the population), in 7th position; however, the relevant bother was among the
      highest reported. Items related to urinary incontinence appeared, when present,
      highly bothersome (87-92% of patients), even though exhibited by a minority of
      the population (5-34%). The mean (+/-SD) IPSS, calculated on 970 patients, was 15
      (+/-7). Two major discrepancies were found in the comparison between IPSS and ICS
      Male. First, terminal dribble, which is not considered in the IPSS, is often
      reported in the ICS-Male. Second, some storage symptoms (nocturia and day-time
      frequency) are less frequently reported in the ICS-Male than in the IPSS, while
      being, in general, highly bothersome. As regards QoL, 95% of subjects declared
      that they would not be completely happy to spend the rest of their life with
      their actual symptoms (ICS-QoL item 33) and 79% that BPH influences their life
      from 'a little' to 'a lot' (ICS-QoL item 30). The mean (+/-SD) IPSS-QoL single
      question score was 3.0 +/- 1.4 (n = 970), and the frequency distribution of
      scores was equivalent to the one detected by the corresponding question of ICS
      QoL (item 33). SF-36, a disease-independent questionnaire about QoL, after a 1
      year follow-up is expected to clarify which among the IPSS and ICS-BPH items
      better describe the impact of BPH on QoL.

PMID- 11598349
TI  - Sexual function in patients with LUTS suggestive of BPH.
AB  - BACKGROUND: Sexual function has been detected in a large sample of Italian
      patients affected by LUTS suggestive of BPH, by means of the ICS-Sex
      questionnaire. RESULTS: A number of 877 questionnaires were returned completely
      filled and were analyzed. Fifty percent of patients declared that their sexual
      life was significantly affected by their urinary symptoms. Difficulty in getting
      erections (58.2% of patients) and ejaculation problems (55.6%) were reported by
      the majority of patients, but the relevant bother was significantly different
      (48.3 and 33.4%, respectively). The ICS-Sex score was significantly associated
      with all the measures of symptoms and QoL employed in the study (IPSS and ICS
      BPH). The urinary symptoms most frequently associated with sexual dysfunction
      were those related to incontinence. CONCLUSIONS: The QUIBUS study shows that
      sexual dysfunctions are commonly complained of by Italian men with LUTS and are
      significantly associated with urinary symptoms, in particular with urine loss.
      These findings support the recommendation by the 5th International Consultation
      on BPH to better evaluate both sexual function and incontinence symptoms in
      patients affected by LUTS suggestive of BPH.

PMID- 11598350
TI  - Relationship of flow rate with symptoms, quality of life and other clinical
      parameters in patients with LUTS suggestive of BPH.
AB  - AIM: The uroflowmetry data of a selected number of patients who took part to the
      QUIBUS study (366 traces selected after quality control by a central panel of
      reviewer) were evaluated for their relationships with age, prostate volume, and
      IPSS and ICS-BPH scores. Waiting time, flow time, voided volume, maximum flow
      rate (Q(max)) and average flow rate (Q(ave)) were the flow variables considered
      for analysis. Only measurements with total voided volume exceeding 100 ml were
      included. RESULTS: An increasing percentage of subjects with voided volume <200
      ml was observed over 65 years of age. Age did not affect neither Q(ave) nor Q(max
      )(p = n.s. at correlation analysis). In particular, Q(max)was <15 ml/s in about
      70% of patients independently of age. Prostate enlargement was inversely
      associated with voided volume, Q(max) and Q(ave), showing a worsening of urinary
      function for increasing values of prostate volume Q(max) was negatively
      correlated with IPSS total score and with most single items with the exception of
      two storage symptoms such as repeated urination and nocturia). Accordingly,
      Q(max) was inversely associated with the total score ICS-BPH for voiding symptoms
      to a higher extent (r = -0.31, p < 0.01) than with the one for storage symptoms
      (r = -0.22, p < 0.01). Flow variables were inversely correlated with IPSS-QoL.
      CONCLUSION: Uroflowmetry and IPSS, although not allowing a definitive diagnosis
      of obstruction, may nonetheless satisfy the clinical need of a rapid, easy and
      accurate tool for the noninvasive screening of LUTS patients.

PMID- 11598354
TI  - Diagnostic efficacy of tumor markers, sonography, and intraoperative frozen
      section for ovarian tumors.
AB  - Using sonography, we classified the adnexal masses of 292 patients into 4
      patterns. Pattern A was benign cystic tumors; B was benign mixed tumors (cysts
      with a smooth solid component); C was malignant mixed tumors (cysts with an
      irregular solid component or thickened septum), and D was solid tumors. We
      diagnosed tumors showing patterns A and B as benign, while patterns C and D
      represented tumors with low malignant potential or actual malignancy. The
      sensitivity and specificity of sonography was 82.2 and 82.1%, respectively, and
      these values were superior to those for tumor markers (CA125, CA19-9, CA72-4).
      Both the sensitivity and specificity of intraoperative frozen sections were the
      highest, showing that this is the most reliable examination. However, 15 of 191
      patients undergoing frozen section were upgraded by the final pathological
      diagnosis. If sonography is performed by an experienced gynecologic oncologist,
      this examination is more reliable than tumor markers. However, intraoperative
      frozen section should still be performed during surgery for patients with ovarian
      tumors.

PMID- 11598355
TI  - Doppler study of the uterine arteries and ovarian stroma in patients with
      polycystic ovary syndrome.
AB  - Doppler analysis of the uterine arteries and ovarian stroma was performed by
      transvaginal ultrasound in 24 patients with polycystic ovary syndrome (PCOS) and
      22 ovulatory women. Vascularization of the ovarian stroma was more abundant in
      patients with PCOS than in control women, but no significant difference in the
      mean pulsatility index (PI) was observed between groups (1.14 +/- 0.28 for the
      PCOS group and 1.05 +/- 0.19 for the control group). The mean PI of the uterine
      arteries was significantly higher in the PCOS group (PI = 3.7 +/- 0.8) than in
      the control group (PI = 2.9 +/- 0.4). In the patients with PCOS, no correlation
      was observed between PI and luteinizing hormone, testosterone or androstenedione
      levels. Obesity had no effect on uterine artery PI, with no significant
      differences in this index when the 3 groups were subdivided into obese and non
      obese groups.

PMID- 11598356
TI  - Comparison of piezo-assisted micromanipulation with conventional
      micromanipulation for intracytoplasmic sperm injection into human oocytes.
AB  - OBJECTIVE: To compare the efficacy of piezo-assisted micromanipulation with
      conventional micromanipulation for intracytoplasmic sperm injection (ICSI) into
      oocytes in patients with impaired semen parameters and no success with in vitro
      fertilization (IVF). STUDY DESIGN: A retrospective randomized study was conducted
      on 204 cycles for 104 couples with piezo-assisted ICSI and 122 cycles for 96
      couples with conventional ICSI. Piezo-assisted ICSI consists of two steps, namely
      penetration of the zona pellucida alone with a piezo-pulse and then puncturing of
      the oolemma with a light negative pressure without piezo, as with conventional
      ICSI. The tips of injection pipettes were prepared after pulling by breakage with
      a scalpel under a microscope, so that the inner diameter at and near the tip was
      5 microm, as for conventional ICSI. RESULTS: Piezo-assisted ICSI demonstrated
      significantly more favorable results, with a fertilization rate of 90.3%
      (conventional ICSI: 83.1%, p < 0.01) and a cleavage rate of 88.1% (conventional
      ICSI: 84.6%, p < 0.01). CONCLUSION: Piezo-assisted ICSI is easy to incorporate a
      spermatozoa exactly into the ooplasm with little deformation of the oocyte during
      insertion. Piezo-assisted ICSI can be used effectively for human oocytes to
      improve the fertilization, cleavage rates.

PMID- 11598357
TI  - NK cell activity and subsets in women with a history of spontaneous abortion.
      Cause, number of abortions, and subsequent pregnancy outcome.
AB  - OBJECTIVE: The aim of this study was to assess the role of NK cells in
      nonpregnant women with a history of spontaneous abortion. STUDY DESIGN: 113
      nonpregnant women with a history of spontaneous abortion were assessed for
      peripheral NK cell activity and percentage of NK cell subsets, in relation to the
      cause of abortions, the number of spontaneous abortions, and subsequent pregnancy
      outcome (n = 56). RESULTS: Neither NK cell activity nor subsets showed a
      significant difference in relation to the cause or number of spontaneous
      abortions. NK cell activity in nonpregnant women who later experienced subsequent
      abortion with normal chromosomes (n = 10) (mean +/- SD: 42.8 +/- 15.8%) was
      relatively higher than that in women with subsequent live birth (control, n = 39)
      (32.1 +/- 13.7%) (p = 0.099). NK cell activity in women who later experienced
      subsequent abortion with abnormal chromosomes (n = 7) (28.7 +/- 21.4%) was the
      same as the level in the control. CONCLUSION: Peripheral NK cell activity or
      subsets during nonpregnant status were not related to the cause or number of
      previous spontaneous abortions. A relation between preconceptional NK cell
      activity and later experiencing abortion with normal chromosomes should be
      further studied.

PMID- 11598358
TI  - Activated protein C resistance in Turkish women with severe preeclampsia.
AB  - The purpose of this study was to investigate the occurrence rate of APC
      resistance (APC-R) with severe preeclampsia in Turkish women. Thirty-two
      consecutive women having severe preeclampsia were included in the study. Thirty
      two healthy pregnant women served as the control group. APC-R assays were
      performed in the third trimester of pregnancy, and 3 and 9 months after delivery.
      APC-R was demonstrated in the third trimester, 3 months and 9 months after
      delivery in 27 (84.4%), 23 (71.9%) and 5 (15.6%) of 32 preeclamptic patients,
      respectively. APC-R rates were significantly higher in preeclamptic group than in
      normal pregnant women in the third trimester of pregnancy (p < 0.05). Decreased
      mean APC activity and also increased APC-R rate was still persisting in
      preeclamptic group for 3 months after delivery. Nine months after delivery, the
      mean APC activity and also APC-R rates approached to the normal pregnant women;
      however, there was a significant difference between both groups (p < 0.05). Our
      results indicate that acquired APC-R may be a contributory factor in the
      pathogenesis of preeclampsia.

PMID- 11598359
TI  - Risk factors for breast cancer among pre- or post-menopausal women in Belo
      Horizonte, Brazil.
AB  - BACKGROUND: Much controversy has been generated about pre- and post-menopausal
      breast cancer patients and investigators have sought to identify whether risk
      factors differ between these two groups. In Brazil, breast cancer is an important
      cause of death among women and there are few analytical studies concerning pre-
      or post-menopausal comparisons. METHODS: A case-control study was carried out at
      the Federal University Hospital, Belo Horizonte, Brazil, to determine if selected
      socio-economic and reproductive risk factors for breast cancer differed between
      pre-menopausal and post-menopausal women. Cases were 300 women with breast
      carcinoma and controls were 600 women with other benign diseases matched for age
      and date of diagnosis, admitted to the same hospital during the same period (1978
      1987). Univariate and multivariate conditional logistic regression analyses were
      performed. RESULTS: Multivariate analysis showed no differences in breast cancer
      risk in pre- and post-menopausal women (risk factors were similar in direction
      and magnitude). Occupation, irregular menstrual cycles, parity, history of breast
      cancer in at least one first-degree female relative, and oral contraceptive use
      had similar associations in both groups. CONCLUSIONS: The present study indicates
      that breast cancer diagnosed before and after menopause has a similar risk
      profile.

PMID- 11598360
TI  - Depot medroxy progesterone acetate: a poor preparatory agent for endometrial
      resection.
AB  - OBJECTIVE: To evaluate the efficacy of depot medroxy progesterone acetate (DMPA)
      as a preparatory agent for endometrial resection. STUDY DESIGN: Endometrial
      resection was performed on 50 women for excessive uterine bleeding. The patients
      were randomly divided into 2 equal groups, with the first group receiving DMPA
      and the second group not receiving any hormonal pre-medication. The resected
      tissue was sent for histopathology and all the patients were followed up
      regularly for a maximum period of 4 years. RESULTS: DMPA was found to increase
      the thickness of the endometrium, making it more fluffy and oedematous. The
      procedure in these patients was associated with a significantly greater fluid
      consumption and deficit. A power analysis showed the overall power of the study
      to be >90%. Forty-four percent of group 1 and 64% of group 2 patients achieved
      amenorrhoea or spotting. Three patients in all underwent a repeat procedure, and
      1 a hysterectomy, following a dissatisfactory result. However, no statistically
      significant difference was found in the outcomes of the 2 groups. CONCLUSION: As
      a preparatory agent, DMPA, seems to have no added benefit. Larger studies are
      required to bring out differences in outcomes, if any.

PMID- 11598361
TI  - Results of a prospective comparative study of transvaginal hydrolaparoscopy and
      chromolaparoscopy in the diagnostics of infertility.
AB  - Transvaginal hydrolaparoscopy (THL) was evaluated in comparison with the already
      established chromolaparoscopy in the detection of tubal factors, adhesions as
      well as endometriosis. 43 infertile patients without previous pelvic operations
      and with an inconspicuous clinical examination were included in a prospective
      comparative study of THL and chromolaparoscopy. THL succeeded in 40 patients
      (93.0%). Both methods showed 100% agreement with regard to tubal factors and
      adhesions. However, only 72/80 tubes (90.0%) could be portrayed by THL. In
      contrast to this, THL failed to identify 8 of 10 laparoscopically verified
      endometrioses (isolated endometriosis of the bladder peritoneum in 2). No
      complications occurred with THL. THL could be the method of choice for the
      clarification of mechanical infertility factors in symptom-free patients with no
      suspicion of pelvic pathologies. Tubal pathologies and/or adhesions (visible
      during THL) should be indications for laparoscopy. In the case of inconspicuous
      genitals during THL and a still unfulfilled desire for offspring postoperatively,
      laparoscopy should be considered in order to exclude the possibility of
      unidentified endometriosis. Retroflexio uteri should at least be a relative
      contraindication for THL. Further studies are necessary to evaluate the role of
      THL in the diagnostic concept of infertility in the future.

PMID- 11598362
TI  - Placenta and myometrium--the two main sources of fibrinolytic components during
      pregnancy.
AB  - OBJECTIVES: Placenta is a known source of some fibrinolytic components in
      pregnancy. The aim of the present study is to find out whether myometrium can be
      a parallel source. STUDY DESIGN: The study group consisted of 34 women (16
      primaparas and 18 multiparas, 39.0 +/- 0.2 years) in the 36-40th week of
      gestation with some obstetric complications: preeclampsia - 11, fetal distress -
      9, breech presentation - 3, placenta previa - 1, repeat caesarean birth - 10
      cases (20 women were the control group). The strips of myometrium as well as
      samples of venous blood and placenta were collected at the time of caesarean
      section. The tissue extracts were prepared. The components of the plasminogen
      activator system were measured, i.e. tissue plasminogen activator (tPA),
      urokinase plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1)
      and plasminogen activator inhibitor 2 (PAI-2). An immunoenzymatic method (ELISA)
      was used. Spearman and Pearson's correlation coefficients were the main tools of
      the statistical analysis. RESULTS: The concentration of the fibrinolytic
      components in blood plasma, placenta and myometrium were as follows (ng/mg of
      total protein): tPA: 0.15 +/- 0.07 (blood plasma), 0.12 +/- 0.05 (placenta), and
      1.42 +/- 1.02 (myometrium); uPA: 0.01 +/- 0.005 (blood plasma), 1.09 +/- 0.25
      (placenta), and 0.52 +/- 0.13 (myometrium); PAI-1: 2.86 +/- 0.90 (blood plasma),
      30.67 +/- 9.31 (placenta), and 22.29 +/- 11.29 (myometrium); PAI-2: 2.86 +/- 0.90
      (blood plasma), 750.89 +/- 170.29 (placenta), and 24.84 +/- 8.03 (myometrium).
      CONCLUSION: Besides placenta, myometrium is another important source of
      fibrinolytic components in pregnancy.

PMID- 11598363
TI  - Effect of betamethasone on computerized cardiotocographic parameters in preterm
      growth-restricted fetuses with and without cerebral vasodilation.
AB  - OBJECTIVE: To verify the effects of maternal corticosteroid administration on
      fetal behavior and heart rate variation using computerized cardiotocography
      (cCTG) in a selected group of growth retarded fetuses. STUDY DESIGN: Fifty
      singleton pregnancies complicated by fetal growth restriction were enrolled in
      the study before 34 weeks of gestation. All of them received two intramuscular
      injections of 12 mg of betamethasone 24 h apart. Fetal heart rate was recorded by
      cCTG before the first injection, and every 24 h for the 3 days following the end
      of the treatment. After Doppler evaluation of cerebral circulation, fetuses were
      divided into a group with and a group without signs of cerebral vasodilation.
      Basal heart rate, short- and long-term variation, percentage of time spent in
      high variability, fetal movements and percentage of small accelerations were
      evaluated. RESULTS: Basal fetal heart rate did not show significant changes.
      Short-term variation and percentage of time spent in high variability
      significantly decreased in fetuses with but not in fetuses without vasodilation.
      Long-term variation and fetal movements significantly decreased in both groups.
      CONCLUSIONS: Maternal administration of betamethasone in growth-retarded fetuses
      with cerebral vasodilation is associated with significant but transitory
      modifications of fetal heart rate variation.

PMID- 11598364
TI  - Influence of melatonin on basal and gonadotropin-stimulated progesterone and
      estradiol secretion of cultured human granulosa cells and in the superfused
      granulosa cell system.
AB  - The aim of this study was to explore the direct action of melatonin (Me) on basal
      and gonadotropin-stimulated progesterone (PG) and estradiol (E2) secretion of
      human granulosa cells (GCs) cultured in serum-free medium and in a superfused GC
      system. Human GCs were isolated from preovulatory follicular fluid aspirated from
      34 women undergoing in vitro fertilization at the University Women's Hospital of
      Tubingen. PG and E2 production was measured in the presence and absence of Me,
      propranolol, LH or FSH using radioimmunoassay. Statistical analysis of the data
      was performed by ANOVA and Newman-Keuls test. Me stimulated E2 secretion in a
      dose-dependent manner. Propranolol did not cause any change in E2 secretion, and
      when given with Me, it only partially blocked but could not entirely prevent E2
      output. There was no statistically significant effect of Me on PG production when
      Me was administered at concentrations between 10(-4) and 10(-8) M. However, at
      10(-3) M Me significantly suppressed PG output of granulosa cells. LH and FSH
      significantly stimulated the secretion of both steroid hormones. Me significantly
      reduced LH- and FSH-induced E2 secretion, as well as LH-stimulated PG output,
      while it caused only a slight, yet significant decrease in PG secretion. In the
      superfused GC system, FSH and LH resulted in a significant stimulatory effect on
      PG release. Me did not modify the stimulatory effect of FSH on PG, while it
      caused some delay in LH-stimulated PG release. Propranolol and Me had no
      stimulatory effect on PG release. On the basis of our results we suggest that Me
      has a direct modulatory effect on basal E2 and gonadotropin-stimulated E2 and PG
      secretion of human GCs. The observed effect may play a physiological role in the
      regulation of GC function during the menstrual cycle.

PMID- 11598365
TI  - Implications of differences in coiling indices at different segments of the
      umbilical cord.
AB  - The purpose of this study was to find out if the coiling density is similar in
      all segments of term singleton umbilical cords. We compared the coiling index
      (coils/cm) at three different segments of 159 cords. There was no statistical
      difference between the coiling indices of the placental and middle segment, but
      significantly increased coiling was found at the fetal end compared with the
      placental and middle segments. Coiling indices were not significantly correlated
      with gestational age, cord length or birth weight. We diagnosed concordant hypo-
      and hypercoiling when the placental and fetal segments had the same density
      classification, and discordant hypo- and hypercoiling when these segments had
      different density classifications. Concordant hypocoiling and hypercoiling were
      found in 4.4 and 6.3% of the cords examined, respectively (total of 10.7%),
      concordant normal coiling in 95 (59.7%) and discordant density classifications in
      29.6%. We concluded that the coiling index should be established in two distinct
      segments and that the spatial configuration of the coils, which protects the
      blood flow in the umbilical cord, might not be measured by coil density only.

PMID- 11598366
TI  - Cirsoid aneurysm after hysterectomy.
AB  - Cirsoid aneurysm, an uncommon abnormal either congenital or acquired
      arteriovenous communication, is described. As massive life-threatening bleeding
      can be a consequence, diagnosis is very important. Earlier, angiography was the
      only imaging method available for visualizing vascular lesions and recent
      developments in imaging techniques have made diagnostic imaging of cirsoid
      aneurysms possible using ultrasonography, color flow mapping, magnetic resonance
      imaging and magnetic resonance angiography. In this report, a patient with
      intrapelvic cirsoid aneurysm posthysterectomy who died 8 h after she had been
      kicked in the abdomen is described and the results obtained by various imaging
      techniques are discussed.

PMID- 11598367
TI  - Complete response of a stage IV mucinous cystadenocarcinoma of the ovary to
      systemic chemotherapy employing paclitaxel and carboplatin.
AB  - BACKGROUND: The survival rate of patients with advanced-stage mucinous
      cystadenocarcinoma of the ovary is dismal and no best treatment is known. We
      report a case of complete response of a stage IV mucinous cystadenocarcinoma of
      the ovary to systemic chemotherapy employing paclitaxel and carboplatin. CASE: A
      51-year-old nullipara diagnosed with International Federation of Gynecology and
      Obstetrics stage IV mucinous cystadenocarcinoma of the ovary underwent
      cytoreductive surgery followed by systemic chemotherapy employing paclitaxel and
      carboplatin every 4 weeks for 3 courses. The patient tolerated chemotherapy well,
      demonstrated a remarkable response showing no evidence of malignancy at a second
      look laparotomy. As a consolidation chemotherapy after negative second-look
      laparotomy, she underwent another three courses of chemotherapy of the same
      regimen, and is showing no evidence of disease. CONCLUSION: Paclitaxel and
      carboplatin may be effective in treating mucinous cystadenocarcinoma of the
      ovary.

PMID- 11598368
TI  - Recurrent molar pregnancy: report of a case with seven consecutive hydatidiform
      moles.
AB  - A case of seven consecutive hydatidiform moles is presented. All of her
      pregnancies revealed a molar pregnancy, 4 of which were demonstrated
      histopathologically. In the context of this study, the potential risk for
      malignant transformation and the obstetric outcome are highlighted. The
      literature regarding recurrent molar pregnancies is reviewed.

PMID- 11598369
TI  - Growth patterns and final height in congenital adrenal hyperplasia due to
      classical 21-hydroxylase deficiency. Results of a multicenter study.
AB  - BACKGROUND: Longitudinal growth and bone age (BA) development are the most
      important clinical parameters for monitoring adequate glucocorticoid replacement
      in children with congenital adrenal hyperplasia (CAH). AIM OF THE STUDY: To
      analyze the growth pattern of patients treated for CAH of the salt wasting (SW)
      and simple virilizing (SV) clinical forms; to evaluate final height as compared
      to reference data and individual target height; to evaluate the course of BA
      development. PATIENTS AND METHODS: A large database of 598 patients with CAH was
      created in 5 Central European countries and growth data of 341 treated patients
      with 21-hydroxylase deficiency were analyzed retrospectively. The patients were
      of Caucasian origin. Centiles were constructed in a cross-sectional manner and an
      additional longitudinal analysis was performed in order to evaluate the pubertal
      growth spurt by applying particular statistical methods (Preece-Baines model).
      RESULTS: The growth of SW CAH patients was impaired in infancy and early
      childhood (0-3 years of age), but followed normal patterns in childhood until
      puberty. In contrast, children with SV CAH had normal patterns of growth in
      infancy and early childhood and were considerably taller than healthy references
      during childhood. In the longitudinal study, peak height velocity in both boys
      and girls was normal, but it occurred at an earlier age than in the standard
      population. The final height of patients with CAH was reduced in comparison to
      both the reference and the individual target height. No correlations were found
      between final height and age at the start of the therapy in SV patients or
      between final height and year of birth. BA was advanced in both types of CAH, but
      more accelerated in SV patients. CONCLUSION: Characteristic growth patterns for
      treated SV and SW CAH children were identified, with a normal pubertal growth
      spurt and reduced final height being observed.

PMID- 11598371
TI  - Molecular analysis of CYP-21 mutations for congenital adrenal hyperplasia in
      Singapore.
AB  - BACKGROUND: Congenital adrenal hyperplasia arising from 21-hydroxylase deficiency
      is associated with mutations in the CYP21 gene on chromosome 6p. This is the
      first report on the mutational spectrum of the CYP21 gene in Singapore. METHODS:
      To catalogue the mutations, ten exons of the CYP21 gene from 28 Singaporean
      patients were analyzed by PCR amplification and direct sequencing. RESULTS:
      Common mutations in descending order were the intron 2 splice site mutation
      (32.7% of the alleles), the I172N mutation (23.1% of the alleles), and the R356W
      mutation (19.2% of the alleles). Two potentially novel mutations were discovered:
      (1) duplication of 111 bp from codon 21 to codon 57 (exon 1) and (2) missense
      mutation (L261P, exon 7). There was generally a good genotype-phenotype
      correlation, allowing accurate prediction of the disease severity.

PMID- 11598370
TI  - Effect of low birth weight on adrenal steroids and carbohydrate metabolism in
      early adulthood.
AB  - AIM: Data are inconsistent whether hyperinsulinemia might be associated with
      adrenal hyperandrogenism in young adults born with low birth weight (LBW).
      METHOD: We investigated the insulin and adrenal steroid production of 70 young
      LBW adults [33 women (birth weight: 1,795 +/- 435 g) and 37 men (birth weight:
      1,832 +/- 337 g)]. Their results were compared to those of 30 controls (14 men,
      16 women), born with normal weight. RESULTS: In LBW women, we measured higher
      basal DHEA (33.5 +/- 13.1 vs. 23.6 +/- 8.7 nmol/l, p < 0.05), DHEAS (8.0 +/- 2.3
      vs. 6.3 +/- 2.1 micromol/l, p < 0.05), androstenedione (8.3 +/- 2.8 vs. 6.0 +/-
      2.2 nmol/l, p < 0.05) and cortisol (0.25 +/- 0.07 vs. 0.20 +/- 0.07 micromol/l, p
      < 0.05) levels and higher insulin response during oral glucose tolerance test
      (log.AUCins: 2.62 +/- 0.06 vs. 2.57 +/- 0.03, p < 0.05). DHEA levels correlated
      with fasting insulin levels (r = 0.45, p < 0.01) and insulin response (r = 0.33,
      p < 0.05). In LBW men, higher cortisol (0.27 +/- 0.06 vs. 0.22 +/- 0.06
      micromol/l, p < 0.01) and SHBG (18.4 +/- 10.4 vs. 12.7 +/- 5.9 nmol/l, p < 0.05)
      levels were found. CONCLUSIONS: Our results suggest that modest hypercortisolism
      is present in young LBW adults. While the endocrine sequel of hypercortisolism
      raised insulin response and hyperandrogenism is detectable in apparently healthy
      young LBW women, it is absent in young LBW men. This suggests that gender
      dependent mechanisms might play a role in the development of insulin resistance
      in LBW adults.

PMID- 11598372
TI  - Leptin concentrations are elevated in newborn infants of diabetic mothers.
AB  - BACKGROUND: Infants of diabetic mothers have been characterized by macrosomia due
      to hyperinsulinism. A relation has been observed between circulating levels of
      leptin and the intrauterine growth pattern. METHODS: We studied the leptin and
      insulin concentrations in the cord blood of 29 newborn infants of mothers with
      type 1 diabetes (iT1DM), 70 newborn infants of mothers with gestational diabetes
      and 105 newborn infants of nondiabetic mothers. RESULTS: There were significant
      differences (p < 0.001) between the 3 groups with the highest leptin levels 24.9
      microg/l (range 1.7-94.1) in infants of mothers with iT1DM and the second-highest
      levels 14.0 microg/l (range 2.6-74.9) in infants of mothers with gestational
      diabetes (iGDM), whereas the control infants had the lowest leptin levels 10.0
      microg/l (range 0.10-45.9). Girls had higher leptin concentrations than boys
      among the iT1DM and control infants. The insulin concentrations were 18.1 mU/l
      (range 1.9-123.3), 6.1 mU/l (range 1.1-51.4) and 3.6 mU/l (range 0.5-21.5) in the
      3 groups (p < 0.001), respectively. A significant correlation was observed
      between leptin and insulin concentrations in iGDM and control infants (r = 0.51;
      p < 0.001 and r = 0.25; p < 0.05). Both absolute and relative birth weights
      correlated with leptin levels in all 3 groups (r = 0.60, p = 0.01 and r = 0.51, p
      = 0.05 in iT1DM; r = 0.51 and 0.56, p < 0.001 in iGDM and r = 0.42 and 0.59, p <
      0.001 in control infants). CONCLUSION: Our results confirm the relation between
      leptin concentrations and birth weight. They also suggest that leptin may be
      involved in the increased accumulation of adipose tissue characteristic of
      infants of diabetic mothers.

PMID- 11598373
TI  - The effect of growth hormone treatment on biochemical indices in hypophosphatemic
      rickets.
AB  - BACKGROUND: Growth hormone (GH) in combination with conventional therapy in
      hypophosphatemic rickets (HR) has been shown to promote renal phosphate (P)
      conservation and to result in a better metabolic control. This study aimed at
      investigating the acute biochemical effects of GH in 7 patients (5 female, 2
      male) with HR aged between 2.16 and 16 years. METHODS: Each patient received the
      following in a sequential design: oral P plus 1,25-dihydroxyvitamin D(3) [1,25
      (OH)(2)D(3)] therapy to determine the optimum doses for baseline requirement
      followed by GH-only therapy and GH +1,25-(OH)(2)D(3) therapy and GH + P +1,25
      (OH)(2)D(3) therapy each for 2 weeks with 1 washout week off treatment in
      between. GH was given at a dose of 0.03 mg/kg/day s.c. on a daily basis. The dose
      of oral P used ranged between 500 and 2,000 mg/day, and the dose of 1,25
      (OH)(2)D(3) ranged between 0.25 and 0.5 microg/day and was kept constant for each
      child throughout the study. RESULTS: Laboratory investigations repeated at the
      end of each treatment, and the first washout period showed that the serum P level
      was highest (2.9 ng/ml) during the GH + P + 1,25-(OH)(2)D(3) period with higher
      serum 1,25-(OH)(2)D(3) levels: 50.9 +/- (SD) 23.4 ng/l. Parathyroid hormone and
      alkaline phosphatase levels did not show a significant difference between the
      periods. The tubular P reabsorption rate showed an insignificant increase during
      GH therapy periods. CONCLUSION: Considering the fixed dose of P and calcitriol,
      it may be concluded that GH added to conventional treatment in HR resulted in a
      slight improvement in the biochemical parameters without any side effects at the
      short term.

PMID- 11598374
TI  - Albright's hereditary osteodystrophy associated with cerebellar pilocytic
      astrocytoma: coincidence or genetic relationship?
AB  - Albright's hereditary osteodystrophy (AHO) is a rare inherited disease
      characterized by skeletal abnormalities, short stature, and, in some cases,
      resistance to parathyroid hormone, resulting in pseudohypoparathyroidism (PHP).
      Heterozygous inactivating mutations of the GNAS1 gene are responsible for reduced
      activity of the alpha subunit of the Gs protein (G(Salpha)), a protein that
      mediates hormone signal transduction across cell membranes. G(salpha) is also
      known to have oncogenic potentials, leading to the development of human pituitary
      tumors and Leydig cell tumors. Here, we report the 1st case, a 3.5-year-old girl,
      with classic AHO phenotype and PHP type 1A associated with a cerebellar pilocytic
      astrocytoma. Coincidence or genetic relationships of both diseases are discussed
      according to molecular findings and current literature.

PMID- 11598375
TI  - Procedure for neonatal screening for congenital adrenal hyperplasia due to 21
      hydroxylase deficiency.
AB  - The value of screening of neonates for congenital adrenal hyperplasia is not
      universally accepted. Procedures for screening are recommended here in order to
      provide a structure to the testing and ultimately bring together data that will
      allow the effect of screening to be judged for benefit or dismissed as no better
      than clinical recognition of the disease state.

PMID- 11598376
TI  - Evaluation of neonatal screening for congenital adrenal hyperplasia.
AB  - Neonatal screening for congenital hypothyroidism has been effective in early
      detection and treatment of the condition. The position with respect to neonatal
      screening for congenital adrenal hyperplasia has been debated for many years.
      Some countries have performed congenital adrenal hyperplasia screening for many
      years, others have conducted pilot studies that were then not adopted. This
      article endeavours to summarize the complex issues behind decisions whether to
      screen or not and summarizes the findings of neonatal congenital adrenal
      hyperplasia screening programmes.

PMID- 11598377
TI  - Involvement of nitric oxide in the regulation of growth hormone secretion in
      dogs.
AB  - Nitric oxide (NO) is a highly reactive gas that has been suggested to function as
      a neurotransmitter in the neuroendocrine system. In this work, we have evaluated
      the role of NO pathways in growth hormone (GH) secretion by assessing the effect
      of L-arginine infusion, a precursor of NO formation, and L-NAME, a nitric oxide
      synthase (NOS) inhibitor. The experiments were carried out on 7 adult beagle
      dogs. A saline infusion was carried out on all the dogs as a control test. L
      arginine (infusion i.v. 10 g in 100 ml of saline, from t = 0 to 30 min) and L
      nitro-arginine-methyl ester, L-NAME (infusion of 300 microg/kg in 120 ml of
      saline, from t = -30 to 45 min) were administered alone and together with growth
      hormone-releasing hormone (GHRH) (i.v. bolus at 0 min, at a dose of 100 microg),
      the synthetic GH secretagogue GHRP-6 (i.v. bolus at 0 min, at a dose of 90
      microg), and the 5-HT1D serotonin receptor agonist sumatriptan, SUM (s.c.
      injection at the dose of 3 mg). Plasma cGH was determined by RIA. Results were
      evaluated by one-way analysis of variance, followed by the Newman-Keuls test for
      multiple comparisons. L-arginine administration resulted in a slight increase in
      plasma cGH in comparison with saline controls. Combined administration of L
      arginine and GHRH enhanced cGH release in comparison with GHRH alone. L-NAME
      alone did not modify baseline cGH levels, but completely suppressed the GH
      release induced by GHRH or GHRP-6. It also strongly reduced, but did not abolish
      the effect of the two peptides (GHRH plus GHRP-6) administered together. Finally,
      administration of the 5-HT1D agonist SUM induced a significant cGH secretion in
      all dogs, a response which was not modified when L-NAME was administered in
      combination with SUM. In conclusion, our data show that inhibition of NO blunts
      both GHRH or GHRP-6-induced cGH release, and are compatible with the hypothesis
      that it acts by decreasing hypothalamic somatostatin release.

PMID- 11598378
TI  - Functional evidence for the presence of type II 5'-deiodinase in somatotropes and
      its adaptive role in hypothyroidism.
AB  - The anterior pituitary contains abundant type II iodothyronine 5'-deiodinase
      (D2). The role of this enzyme in mediating thyroid hormone action in the
      pituitary has been proven only for thyrotropes, although there is evidence that
      it exists in other cell types, including somatotropes and lactotropes. Here we
      investigated the potential of D2 to mediate thyroid hormone regulation of growth
      hormone (GH). Using GH mRNA as an end point, we demonstrate that in hyperthyroid
      states GH mRNA levels are stimulated by triiodothyronine (T(3)) generated via D1,
      whereas in hypothyroidism, when D2 activity is markedly increased, GH mRNA is
      more responsive to tetraiodothyronine (T(4)) in a propylthiouracil-insensitive,
      reverse T(3)-suppressible manner. Under short-term hyperthyroid conditions, GH
      levels correlate with plasma T(3); in contrast, the correlation is not observed
      in hypothyroidism, a condition in which plasma T(3) levels are too low to account
      for the response. These results add support to the concept that D2 is present in
      the pituitary and that the enzyme plays an important role in mediating
      stimulation of GH by thyroid hormones, particularly in hypothyroid states in
      which they could alleviate the impact of hypothyroxinemia on GH secretion.

PMID- 11598379
TI  - Estrogen modulation of the cyclic AMP response element-binding protein pathway.
      Effects of long-term and acute treatments.
AB  - Actions of estrogen include mechanisms leading to alterations in gene
      transcription that may be independent of nuclear estrogen receptors, as well as
      those involving direct action of the estrogen receptor on the genome. Also, the
      influence of estrogen in the brain appears to extend well beyond areas associated
      with reproduction and may include forebrain areas linked to affective and
      cognitive behaviors. We investigated the effects of acute and long-term estradiol
      benzoate (E2) treatment on total and phosphorylated cyclic AMP responsive element
      binding (CREB) protein levels and on cyclic AMP response element (CRE)-DNA
      binding in forebrain areas of ovariectomized (OVX) rats. Long-term E2 treatment
      increased CRE-DNA binding in the amygdala but not in hippocampus, frontal cortex,
      or cerebellum. The increase in CRE-DNA binding in the amygdala was associated
      with increased levels of total and phosphorylated CREB (pCREB) protein during
      protracted E2 exposure. To localize the estrogenic effect in the amygdala and
      determine if an effect in one hippocampal region was masked by a lack of effect
      in another subregion, we performed immunolabeling of pCREB in brain structures of
      chronically treated OVX animals with or without E2. This treatment resulted in a
      significant increase in relative total immunolabeled nuclei in the anteroventral
      subdivision of the medial amygdala. In the hippocampus, a significant increase in
      relative total immunolabeled nuclei was seen in the CA1 and CA3 regions, but not
      in the dentate gyrus or hilus of the dentate gyrus. Acute E2 treatment resulted
      in increased CRE-DNA binding in the frontal cortex but not in amygdala,
      hippocampus, or cerebellum. However, no changes in levels of total CREB or pCREB
      protein were observed in the frontal cortex under E2 treatment. No changes were
      observed either in basal or cAMP-stimulated protein kinase A (PKA) activity or in
      PKA-alpha catalytic subunit immunoreactivity in the amygdala or the frontal
      cortex. Our study indicates that both long-term and acute treatments with
      estrogens influence the function of CREB in specific brain structures.

PMID- 11598380
TI  - Regulation of Dexras1 expression by endogenous steroids.
AB  - Dexras1, a newly identified member of the Ras superfamily of proteins, was
      discovered in AtT-20 corticotrope cells because its expression was induced in
      response to glucocorticoids (dexamethasone; Dex). As yet, the function of Dexras1
      is unknown, but its rapid induction in response to glucocorticoids suggests the
      possibility that it may be involved in negative feedback regulation of
      corticotropin secretion. To better understand the control of Dexras1 expression,
      possible effects of other steroid hormones on its expression were studied in both
      AtT-20 cells and in mouse pituitaries. AtT-20 cells were treated with each of 6
      steroids [aldosterone, corticosterone (Cort), Dex, beta-estradiol (E(2)),
      progesterone and testosterone] for 2 h. Dexras1 expression was assessed using
      both reverse transcription polymerase chain reaction (RT-PCR) and Northern
      analysis. Expression of the gene was only induced in response to glucocorticoid
      treatment (Dex or Cort). The 6 steroids were also injected into mice, pituitaries
      were harvested and total RNA was obtained for RT-PCR analysis. Surprisingly,
      treatment with E(2), not only injection of glucocorticoids, induced Dexras1
      expression in mouse pituitary. Other steroids were without effect. The results
      suggest that in AtT-20 corticotropes, Dexras1 expression is only induced by
      glucocorticoid-type steroids. In pituitary glands of mice, the gene's expression
      is also responsive to E(2). We conclude that either Dexras1 expression in
      corticotropes from normal mice is regulated differently from that in AtT-20
      cells, or that Dexras1 is also expressed in other pituitary cells than
      corticotropes.

PMID- 11598381
TI  - Differential expression of calcium channel subtypes in the bovine adrenal
      medulla.
AB  - This study aimed at determining the distribution and expression levels of
      different subtypes of Ca(2+) channels in the bovine adrenal medulla, and whether
      individual subtypes were more abundant in chromaffin cells exhibiting an
      adrenergic or a noradrenergic phenotype. In situ hybridization using riboprobes
      specific for the pore-forming Ca(2+) channel alpha(1D) (L-type channel),
      alpha(1B) (N-type channel), and alpha(1A) (P/Q-type channel) subunits of bovine
      chromaffin cells showed a broad distribution of the three transcripts in adrenal
      medulla tissue. However, a tissue-specific expression pattern of individual
      subunits was found; whereas alpha(1B) mRNA was homogeneously distributed
      throughout the medulla, alpha(1D) and alpha(1A) transcripts were present at
      higher densities in the internal medullary area, far away from the adrenal
      cortex. These results were corroborated by comparative analysis of the alpha(1B),
      alpha(1D), and alpha(1A) products amplified by RT-PCR from total RNA extracted
      from small pieces of tissue dissected out from external or internal medullary
      areas. Interestingly, immunohistochemical experiments performed in adrenal gland
      sections, using antidopamine-beta-hydroxylase and anti-phenylethanolamine-N
      methyltransferase antibodies, indicated a higher density of noradrenergic over
      adrenergic chromaffin cells in the internal medullary region. These results
      provide direct evidence in favor of a heterogeneous distribution of Ca(2+)
      channel subtypes in the adrenal medulla, in agreement with previous functional
      data showing that blockade of the high K+ -elicited responses by dihydropyridines
      was greater in noradrenergic than in adrenergic chromaffin cells. These
      differences may be relevant for the differential release regulation of each
      catecholamine under physiological and pathophysiological conditions.

PMID- 11598382
TI  - Dual effect of melatonin on gonadotropin-releasing-hormone-induced Ca(2+)
      signaling in neonatal rat gonadotropes.
AB  - In neonatal rat gonadotropes, melatonin inhibits gonadotropin-releasing-hormone
      (GnRH)-stimulated increase in intracellular Ca(2+) concentration ([Ca(2+)](i));
      in cells transfected with the Mel1a melatonin receptor, however, melatonin has
      been shown to potentiate agonist-stimulated [Ca(2+)](i) increase. To elucidate
      this discrepancy, we investigated the effects of melatonin in neonatal
      gonadotropes over a wide range of melatonin concentrations. Nystatin perforated
      patch recording of Ca(2+)-dependent potassium currents was used to monitor GnRH
      induced [Ca(2+)](i) changes. In 32% of cells, increasing melatonin concentrations
      in the range of 1 pM to 100 nM prolonged the latency of, and inhibited GnRH (10
      nM)-stimulated [Ca(2+)](i) increases in a concentration-dependent manner. In the
      remaining 68% of cells, the Ca(2+) increase elicited by exposure to 10 nM GnRH
      was also inhibited by picomolar concentrations of melatonin, but at nanomolar
      concentrations the inhibitory effect disappeared and melatonin was only able to
      prolong the latency of the response. This dual effect of melatonin however was
      not observed in cells stimulated with lower (2 nM) GnRH concentrations; in that
      case, melatonin was inhibitory at all concentrations tested with an IC(50) of
      about 30 pM. In contrast, application of nanomolar concentrations of melatonin
      resulted in potentiation of the GnRH-induced Ca(2+) increase in a small
      population of gonadotropes which did not respond by inhibition or prolonged
      latency. These results indicate that in neonatal gonadotropes, melatonin has both
      inhibitory and potentiating effects on GnRH-stimulated [Ca(2+)](i) increases.
      Ranges of concentrations needed to produce either effect suggest that two
      distinct G proteins may be involved, as already observed in transfected cells.

PMID- 11598383
TI  - Improving influence of insulin on cognitive functions in humans.
AB  - Insulin receptors have been identified in limbic brain structures, but their
      functional relevance is still unclear. In order to characterize some of their
      effects, we evaluated auditory evoked brain potentials (AEP) in a vigilance task,
      behavioral measures of memory (recall of words) and selective attention (Stroop
      test) during infusion of insulin. The hormone was infused at two different rates
      (1.5 mU/kg x min, "low insulin", and 15 mU/kg x min, "high insulin"), inducing
      respectively serum levels of 543 +/- 34 and 24,029 +/- 1,595 pmol/l. This
      experimental design allowed to compare cognitive parameters under two conditions
      presenting markedly different insulin levels, but with minimal incidence on blood
      glucose concentrations since these were kept constant by glucose infusion. A "no
      insulin treatment" group was not included in order to avoid leaving patients
      infused with glucose without insulin treatment. Measures were taken during a
      baseline phase preceding insulin infusion and every 90 min during the 360 min of
      insulin infusion. Compared with "low insulin", "high insulin" induced a slow
      negative potential shift in the AEP over the frontal cortex (average amplitude,
      high insulin: 0.27 +/- 0.48 microV; low insulin: 1.87 +/- 0.48 microV, p <
      0.005), which was paralleled by enhanced memory performance (words recalled, high
      insulin: 22.04 +/- 0.93; low insulin: 19.29 +/- 0.92, p < 0.05). Also, during
      "high insulin" subjects displayed enhanced performance on the Stroop test (p <
      0.05) and expressed less difficulty in thinking than during "low insulin" (p <
      0.03). Results indicate an improving effect of insulin on cognitive function, and
      may provide a frame for further investigations of neurobehavioral effects of
      insulin in patients with lowered or enhanced brain insulin, i.e., patients with
      Alzheimer's disease or diabetes mellitus.

PMID- 11598384
TI  - Effects of hematocrit and blood flow distribution on solute clearance in hollow
      fiber hemodialyzers.

PMID- 11598385
TI  - Lipid formulations of polyene antifungal drugs and attenuation of associated
      nephrotoxicity.
AB  - Amphotericin B is an effective broad-spectrum antifungal agent, but various side
      effects, especially nephrotoxicity, have restricted its use. Recently, lipid
      formulations of amphotericin B have been developed in order to reduce its toxic
      side effects. Clinical trials, although in the early stages, suggest promising
      results, and that some of these lipid formulations are potent and less toxic,
      even at higher doses. We summarize herein the existing information about newer
      lipid formulations of polyene antifungal drugs, which could attenuate associated
      nephrotoxicity.

PMID- 11598386
TI  - Gene regulation and targeting in the kidney: relevance to renal physiology and
      pathophysiology.

PMID- 11598387
TI  - The risk of renal stone formation during and after long duration space flight.
AB  - BACKGROUND: The formation of a renal stone during space flight may have serious
      negative effects on the health of the crewmember and the success of the mission.
      Urinary biochemical factors and the influence of dietary factors associated with
      renal stone development were assessed during long duration Mir Space Station
      missions. METHODS: Twenty-four-hour urine samples were collected prior to, during
      and following long duration space flight. The relative urinary supersaturation of
      calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric
      acid were determined. RESULTS: Changes in the urinary biochemistry of crewmembers
      during long duration spaceflight demonstrated increases in the supersaturation of
      the stone-forming salts. In-flight hypercalciuria was evident in a number of
      individual crewmembers and 24-hour dietary fluid intake and urine volume were
      significantly lower. During flight, there was a significant increase in brushite
      supersaturation. CONCLUSIONS: These data suggest acute effects of space flight
      and postflight changes in the urinary biochemistry favoring increased
      crystallization in the urine. The effects of dietary intake, especially fluid
      intake, may have a significant impact on the potential for renal stone formation.
      Efforts are now underway to assess the efficacy of a countermeasure to mitigate
      the increased risk.

PMID- 11598388
TI  - Parathyroidectomy in chronic renal failure: has medical care reduced the need for
      surgery?
AB  - Subtotal or total parathyroidectomy is sometimes required for the management of
      severe secondary or tertiary hyperparathyroidism. Advances in medical and
      dialysis care may have a beneficial effect on hyperphosphatemia and vitamin D
      status, which could, in turn, reduce the need for parathyroidectomy. We used the
      United States Renal Data System to test this hypothesis. We found that the
      percentage of prevalent end-stage renal disease patients undergoing subtotal or
      total parathyroidectomy has declined significantly from 1988 to 1998. It is
      likely that improved medical and dialysis care has enabled this result.

PMID- 11598389
TI  - Differential effects of FMLP-activated neutrophils from patients with IgA
      nephropathy enhanced endothelin 1 production of glomerular mesangial cells.
AB  - BACKGROUND: Neutrophil infiltration in the glomeruli is common in patients with
      IgA nephropathy (IgAN). The pathogenetic roles of the infiltrated neutrophils and
      their relationship with glomerular mesangial cells, however, are not clear.
      METHODS: We examined the effects of coculture with N-formyl-methionyl-leucyl
      phenylalanine (FMLP) activated neutrophils on the viability, endothelin 1 (ET-1)
      production, and ET-1 mRNA expression of rat glomerular mesangial cells.
      Neutrophils were isolated from 15 IgAN patients, from 13 patients with non-IgA
      mesangial proliferative glomerulonephritis (MsPGN), and from 10 normal controls.
      RESULTS: The ET-1 production by mesangial cells was significantly higher after
      stimulation with FMLP-activated neutrophils from IgAN patients than that of MsPGN
      patients and normal controls, and this effect was significantly abolished by
      pretreating mesangial cells with superoxide dismutase and partly abolished by
      catalase. The ET-I mRNA expression of mesangial cells showed a parallel increase
      with ET-1 protein. The trypan blue exclusion test showed significant mesangial
      cell death after stimulation with FMLP-activated neutrophils as compared with
      quiescent neutrophils, and the cell death was also prevented by superoxide
      dismutase but not catalase. The FMLP-activated neutrophils from IgAN patients
      produced more superoxide than those of MsPGN patients and normal controls.
      CONCLUSION: The FMLP-activated neutrophils from patients with IgAN have
      differential effects in enhancing the cell death and the ET-1 production of
      glomerular mesangial cells through the release of superoxide.

PMID- 11598390
TI  - Renal involvement induced by human parvovirus B19 infection.
AB  - In an attempt to clarify the renal involvement induced by human parvovirus B19
      (HPB19) infection, we investigated 6 adult patients with transient urinary
      abnormalities followed by erythema infectiosum. All patients had HPB19-specific
      IgM antibody and showed mild proteinuria of 0.2-1.2 g/day with or without
      microscopic hematuria. In 5 patients a decrease of complement was present, and in
      2 the circulating immune complex levels were elevated. All patients showed mild
      or moderate endocapillary proliferation with leukocytic infiltrates in glomeruli
      and leukocytic infiltrates with edema around interlobular arteries and
      arterioles. Immunofluorescence microscopy revealed C3c deposits with
      immunoglobulins along the glomerular capillary walls and in the walls of small
      arteries and arterioles. Electron microscopic studies showed swelling of the
      endothelial cells and small electron-dense deposits in mesangium (in all 6
      patients) and subendothelium (in 5 of 6 patients). However, HPB19 VP1 and VP2
      capsid antigens were not demonstrated in the glomerulus or the vascular wall in
      any patient. These findings suggest that the renal lesions caused by an immune
      complex mediated phenomenon would be closely correlated with the HPB19 infection,
      although the precise mechanism is not entirely clear, and that in adults HPB19
      should be thought of as a possible cause of acute postinfectious
      glomerulonephritis.

PMID- 11598391
TI  - Potential value of CML-Hb in predicting the progression of bone cysts in dialysis
      related amyloidosis.
AB  - BACKGROUND/AIM: Carboxymethyllysine is one of the common advanced glycation end
      products in vivo. In a previous report, we were the first to describe the
      increase of circulating carboxymethyllysine-hemoglobin (CML-Hb) levels in
      hemodialysis patients, particularly in patients with dialysis-related amyloidosis
      (DRA). The aim of this study was to investigate the predictive value of CML-Hb in
      the progression of DRA using computed tomography images of 2-year or 3-year
      follow-up periods of patients with amyloid bone cysts at the hip joint. METHODS:
      Circulating CML-Hb levels were measured as previously reported, and computed
      tomography scanning was conducted from 1996 to 1998 or 1999 in 57 hemodialysis
      patients whose original renal disease had been confirmed to be nondiabetic.
      Patients who showed a new growth of cysts or a growth rate of 30% or more were
      classified as progressive cases, while the other patients were classified as
      nonprogressive cases. RESULTS: (1) The circulating CML-Hb levels showed a strong
      correlation with the DRA score by multiple regression analysis, and (2) patients
      with progression of amyloid cysts showed a significantly higher circulating CML
      Hb level than patients without progression. CONCLUSION: Based upon these results,
      we conclude that measurement of circulating CML-Hb levels has a potential value
      in both judgment of the clinical state and prediction of progression of DRA in
      hemodialysis patients.

PMID- 11598392
TI  - Vitamin E inhibits proliferation of primary cultured human mesangial and
      endothelial cells.
AB  - BACKGROUND: Vitamin E (VE) has been used as an antioxidant and has been suggested
      to inhibit the proliferation of mesangial cells in rat and vascular endothelial
      cells. The direct effect of VE on primary cultures of mesangial cells (MC) and
      endothelial cells (EC) from the human glomerulus was studied. METHODS: (1) MC (in
      17 or 2.5% FCS DMEM) or EC (in 10 or 5% FCS CSC) at 5,000 cells/well was
      incubated with serial concentrations of VE from 0.05 to 50 microg/ml (0.06 to 60
      IU/l). (2) MC was cocultured with 160, 80, 40 or 20 microg/ml of low-density
      lipoprotein (LDL) or oxidized LDL (ox-LDL) in 17 or 2.5% FCS DMEM with or without
      VE. After 3 days of incubation at 37 degrees C in 5% CO(2), cell proliferation
      was measured by the Premix WST-1 Assay System. RESULTS: The concentration of VE
      that significantly inhibited the proliferation of MC cultured in 17 or 2.5% FCS
      DMEM was 50 or 2.5 microg/ml (60 or 3.0 IU/l), respectively, and that of EC in 10
      or 5% FCS medium was 50 or 25 microg/ml (60 or 30 IU/l). VE at 25 microg/ml (30
      IU/l) inhibited the LDL proliferative effect on MC cultured in 2.5 FCS DMEM by
      21.79-93.21% in a LDL concentration-dependent manner. There was little difference
      between the effects of LDL and ox-LDL on the VE inhibitory effect on MC under our
      experimental conditions. CONCLUSION: VE at low concentrations had no effect on
      the proliferation of both MC and EC, but at high concentrations, it showed an
      inhibitory effect on both cells.

PMID- 11598393
TI  - Folate supplementation in peritoneal dialysis patients with normal erythrocyte
      folate: effect on plasma homocysteine.
AB  - The possible role of folate supplementation in reducing hyperhomocysteinemia in
      dialysis patients has been reported in several recent papers. However, scant data
      are available for peritoneal dialysis patients; besides, none of these studies
      investigated either the role of intraerythrocyte folate concentration or the
      presence of side effects caused by folate administration. Sixty-six peritoneal
      dialysis patients with hyperhomocysteinemia (>15 micromol/l) and normal folate
      status (as assessed by erythrocyte folate level >600 nmol/l) were randomly
      allocated to receive either oral folate (5 mg/day) or no vitamin supplementation.
      After 2 months of therapy, patients were requested to answer a questionnaire
      investigating the occurrence of symptoms possibly related to folate
      supplementation. Twenty-nine treated patients and 30 untreated controls completed
      the study. In the treated patients, serum and erythrocyte folate increased
      significantly (p < 0.0001) (respectively from 10.6 +/- 4.9 to 237 +/- 231 nmol/l
      and from 1,201 +/- 297 to 2,881 +/- 294 nmol/l) to levels at the uppermost limit
      of detection by laboratory methods. Serum vitamin B(12) levels did not change.
      Plasma homocysteine levels decreased from 54 +/- 32 to 23 +/- 14 micromol/l after
      folate supplementation and remained unchanged in the control group. After 4
      months of folate therapy, homocysteine concentration was within the normal range
      in 5 patients (17%) and below 30 micromol/l in the other 21 (72%). Folate therapy
      resulted in a decrease in homocysteine of more than 50% in 45% of the patients
      and decrease of more than 20% in a further 38%. No significant symptoms were
      reported. Thus, serum and erythrocyte folate increase confirms that normal folate
      levels are inadequate in dialysis patients, even if serum and erythrocyte levels
      before folate supplementation cannot predict the effect on homocysteine plasma
      levels.

PMID- 11598394
TI  - Evolution pattern of auto-antibodies against oxidized low-density lipoproteins in
      renal transplant recipients.
AB  - An increased degree of oxidative stress in renal transplant recipients and a
      possible role of ciclosporin A (Cs-A) immunosuppressive therapy in this process
      have already been described. However, prospective data using in vivo markers and
      the influence of Cs-A in the oxidizability of low-density lipoprotein (LDL) are
      scarce. We aimed at investigating in this prospective study the evolution pattern
      of auto-antibodies directed against malondialdehyde-modified LDL (MDA-LDL) and
      Cu2+-oxidized LDL in 28 stable renal transplant recipients on Cs-A
      immunosuppressive therapy before and after 3 successive years of renal
      transplantation. Also, the effect of enrichment of LDL with Cs-A on the
      susceptibility of LDL to in vitro oxidation was tested. The results showed a
      significant increase of both auto-antibody titres (MDA-LDL and Cu2+-oxidized LDL)
      after 1 year, and the values remained high during the 2nd and the 3rd year
      following transplantation. The yearly mean relative variations of auto-antibodies
      against MDA-LDL and Cu2+-oxidized LDL during the follow-up period were 133, 149,
      and 137%, and 111, 115, and 117%, respectively. A significant correlation was
      observed during the 1st year between Cs-A trough blood level and Cu2+-oxidized
      LDL auto-antibody: r = 0.04 (p = 0.046). Incorporation of Cs-A into LDL from
      healthy volunteers showed no changes during the lag phase in comparison with Cs-A
      free LDL, indicating that Cs-A had no effect on in vitro LDL oxidizability. Our
      results suggest that Cs-A may be involved earlier in the LDL oxidation, but the
      mechanism by which it acts is still unclear.

PMID- 11598395
TI  - Associations of micro-albuminuria with intra-uterine growth retardation.
AB  - BACKGROUND/AIM: Micro-albuminuria is associated with insulin resistance and a
      high blood pressure and predicts an increased risk of cardiovascular disease in
      both diabetic and non-diabetic populations. Relationships have been described for
      micro-albuminuria with both low birth weight and short stature in adulthood. We
      have tested the hypothesis that micro-albuminuria in non-diabetic adults may be
      associated with markers of intra-uterine growth retardation. METHODS: We measured
      the urinary albumin excretion rate in 818 men and women from three populations,
      in whom detailed records of birth weight were available, of whom 354 had records
      of length at birth to provide an estimate of the ponderal index. RESULTS: The
      albumin excretion rates were higher in men than in women (5.1 vs. 3.8 microg/min)
      and were related to age (r = 0.23, p < 0.001) and body mass index (r = 0.08, p =
      0.02) as well as fasting plasma glucose and blood pressure. Considered as a
      continuous variable, the albumin excretion rate was not related to any measure of
      size at birth or to adult height. Fifty-four subjects (6.6%) were micro
      albuminuric (albumin excretion rate > or = 20 microg/min), and these subjects
      were thinner at birth than normo-albuminuric subjects (12.9 vs. 13.8 oz/in3, p =
      0.09). Compared to those subjects whose ponderal index had been in the upper
      third of the distribution, people whose ponderal index had been in the lower
      third of the distribution had an odds ratio for micro-albuminuria of 3.1 (p for
      trend 0.05). CONCLUSION: The association between micro-albuminuria, insulin
      resistance, and coronary heart disease may be a consequence of growth retardation
      representing a common antecedent.

PMID- 11598396
TI  - Vitamin D receptor gene polymorphism detected by digestion with Apa I influences
      the parathyroid response to extracellular calcium in Japanese chronic dialysis
      patients.
AB  - BACKGROUND: To play its physiological role, 1,25(OH)2D3 must bind to a specific
      vitamin D receptor (VDR) in the nucleus. We have previously reported that VDR
      gene polymorphism influences the parathyroid function in patients with end-stage
      renal disease (ESRD). In the present study, we have investigated the relationship
      between the parathyroid responsiveness and VDR gene polymorphism, as detected by
      the Apa I restriction enzyme, by changing the concentration of Ca2+ in the
      dialysate. METHODS: 58 Japanese ESRD patients undergoing renal replacement
      therapy in our institution were evaluated. Genomic DNA was extracted from
      peripheral leukocytes and digested at the intron between exon 8 and exon 9 of the
      VDR gene using Apa I enzyme. Then alleles were classified into genotype A
      (undigested allele) and genotype a (digested allele). Extracellular ionized
      calcium ([Ca2+]e), serum phosphate, and intact parathyroid hormone (PTH) were
      measured before and after each hemodialysis (HD) session with dialysates having
      different concentrations of Ca2+ (1.5 or 1.25 mmol/l). The significance of
      differences in statistical analyses was defined within confidence limits of 5.0%.
      RESULTS: The AA, Aa, and aa genotypes were observed in 7/58 patients (12.1%),
      23/58 patients (39.6%), and 28/58 patients (48.3%), respectively. The PTH
      reduction after HD with the 1.5-mmol/l Ca dialysate did not differ significantly
      between group AA+Aa and group aa. On the other hand, the PTH increase was
      significantly higher in group aa than in group AA+Aa after HD with the 1.25
      mmol/l Ca dialysate (p = 0.0107), despite a similar PTH level before HD.
      Similarly, the percent increase of PTH after HD with the 1.25-mmol/l Ca dialysate
      was significantly higher (p = 0.0112) in group aa (50.2 +/- 9.4%) than in group
      AA+Aa (19.7 +/- 7.2%). There were no significant differences between the two
      groups in [Ca2+]e nor in serum phosphorus (Pi) before and after HD with either
      dialysate. Group AA+Aa and group aa did not show statistically significant
      differences in age, female/male ratio, ratio of diabetic nephropathy, or dialysis
      period. CONCLUSIONS: The study results showed that the patients in group aa were
      more sensitive to changes in [Ca2+]e than those in group AA+Aa. Moreover, they
      suggested that the VDR gene polymorphism may affect parathyroid responsiveness to
      changes in [Ca2+]e, which in turn may influence onset and progression of
      hyperparathyroidism in ESRD patients.

PMID- 11598397
TI  - Renal mineral handling in normal rats treated with sevelamer hydrochloride
      (Renagel), a noncalcemic phosphate binder.
AB  - The effects of sevelamer hydrochloride (Renagel); hereafter referred to as
      sevelamer), a noncalcemic phosphate binder, on renal mineral handling were
      examined in rats. Normal rats were fed a diet containing 0.3, 1, 3, and 5%
      sevelamer for 8 days, and serum, urine, and the immunohistochemical localization
      of the type II Na/Pi cotransporter protein in the kidney were analyzed. Rats
      treated with 3 or 5% sevelamer showed significant decreases in serum phosphorus
      (P) and parathyroid hormone (PTH) levels, with no changes in serum calcium (Ca),
      magnesium (Mg), or 1,25(OH)2D3 levels. Increases were observed in urinary
      excretions of Ca and Mg associated with a reduction in the PTH level in rats
      treated with 3 or 5% sevelamer. Rats treated with 1% or higher concentrations of
      sevelamer showed significant dose-dependent and marked reductions of the urinary
      P excretion, and the tubular reabsorption of P was maximized to almost 100% in
      the 5% sevelamer group. The hypophosphaturia in rats treated with 3 or 5%
      sevelamer was accounted for by the reductions in serum PTH and P per se, and
      immunohistochemical analysis showed that the expression of type II Na/Pi
      cotransporter protein was markedly increased at the brush border membranes of the
      deep and superficial nephrons in rats treated with 5% sevelamer as compared with
      rats given a normal diet. In conclusion, sevelamer rapidly lowered serum P and
      PTH levels in normal rats. Sevelamer treatment also produced a marked
      hypophosphaturia associated with translocation of type II Na/Pi cotransporter
      protein and increased urinary Ca and Mg excretions by the reduction of PTH.

PMID- 11598398
TI  - Does methylene blue protect the kidney tissues from damage induced by ciclosporin
      A treatment?
AB  - Ciclosporin A (CsA) is the first-choice immunosuppressant universally used in
      allotransplantation and autoimmune diseases. However, it has been demonstrated
      that this drug produces negative side effects in several organs and in particular
      in the lymphoid organs and in the kidney. It has been suggested that the CsA
      causes deleterious effects because it increases the oxygen free radical
      production. Here we wanted to test whether antioxidants protect the kidney
      parenchyma from the toxicity induced by CsA. We used methylene blue (MB), because
      it inhibits the formation of oxygen free radicals. The study was carried out in
      four groups of Wistar rats. Group I animals were intraperitoneally injected with
      MB (1 mg/kg/day) for 21 days; group II animals were subcutaneously injected with
      CsA (15 mg/kg/day) for 21 days; group III animals were treated with CsA combined
      with MB at the same doses and for the same periods as groups I and II, and group
      IV animals were injected subcutaneously with olive oil for 21 days as controls.
      The kidneys and the thymuses were subsequently removed and examined by
      conventional morphological staining (hematoxylin-eosin and Masson's trichrome)
      and enzymatic (NADPH-diaphorase, cytochrome, c oxidase, and superoxide anion
      production) and immunoenzymatic (inducible nitric oxide synthase--iNOS,
      endothelial nitric oxide synthase--eNOS) techniques. The thymuses were used to
      check the persistence of CsA-immunosuppressive effects during MB administration.
      Group I, III, and IV animals showed a normal kidney architecture and low levels
      of NADPH-diaphorase and of superoxide anion in all structures studied (proximal
      and distal tubules, glomeruli and the Henle loops). The cytochrome c oxidase
      showed a strong activity in proximal tubules, a moderate activity in distal
      tubules, and a weak activity in glomeruli and in the Henle loops. The expression
      of iNOS was weak in the proximal tubular epithelial cells and negative in the
      glomeruli, while eNOS was found to be moderately positive in the glomeruli and in
      the interstitial arteries, but not in the tubules and in the Henle loops.
      Degenerative changes with tubulointerstitial injury in the cortex of CsA-treated
      kidneys (group II) and increases of NADPH-diaphorase levels, iNOS activity, and
      superoxide staining were found in all structures. The expression of eNOS did not
      change in group I, III and IV animals. MB combined with CsA prevented the
      degenerative changes caused by CsA, preserving the structural, enzymatic, and
      immunoenzymatic integrity of the renal parenchyma. The mechanism by which MB
      exerts its protective action is not yet clear, but it seems to be due to its
      ability to inhibit xanthine oxidase and to quench nitric oxide production.
      Moreover, these data have been also supported by the following: (1) the
      superoxide anion levels were very high after CsA treatment and reduced after CsA
      MB treatment, and (2) the iNOS levels increased in CsA-treated rats and showed
      normal levels after CsA-MB treatment. Moreover we demonstrated that MB
      administration did no compromise the CsA immunosuppressive effects, since the
      thymus showed a cytoarchitecture like that observed in CsA-treated rats.

PMID- 11598399
TI  - Management of hyperinsulinemia with diazoxide in an elderly hemodialysis patient.
AB  - An elderly, nondiabetic, chronic hemodialysis patient is described here who had
      profound hypoglycemia for a myriad of reasons including renal failure,
      malnutrition, and quinine use. Furthermore, by biochemical parameters the patient
      had hyperinsulinemia, which was consistent with the diagnosis of an insulinoma.
      However, a tumor was not identified by noninvasive radiologic imaging as is often
      the case and the patient was not a candidate for surgical exploration. Diazoxide
      at a dose of 225 mg/day was used to successfully manage this patient's
      hypoglycemia. Previous experience with the use of diazoxide for hyperinsulinism
      in the hemodialysis population is limited and this case is the second report of
      its use for this purpose.

PMID- 11598400
TI  - TINU syndrome associated with reduced complement levels.
AB  - The TINU syndrome (tubulointerstitial nephritis and uveitis) was first described
      by Dobrin et al. in 1975. Since then, more than 50 cases have been documented
      each with diverse immunopathogenetic and genetic characteristics. The aim of this
      report is to describe a case of TINU associated with reduced complement levels.
      We profile a 48-year-old white female with persistently reduced C4 complement
      levels during the acute phase of the pathology and with an unaltered immunologic
      profile. Renal biopsy evidenced a significant lymphocytic interstitial
      infiltration. Immunohistochemical studies of the interstitium infiltrates was
      positive for the presence of the T (CD3) markers (CD4 > CD8). Steroid therapy
      yielded a complete regression of the symptomatology with normalization of the
      complement levels. We suggest that it is possible to hypothesize that the various
      immunologic alterations associated with TINU, including the transient reduction
      complement levels, may be secondary to multiple inflammatory mechanisms which
      express themselves throughout the pathology.

PMID- 11598402
TI  - HOMA index to assess insulin resistance in renal failure patients.

PMID- 11598401
TI  - Urinary podocytes in primary focal segmental glomerulosclerosis.
AB  - BACKGROUND/AIM: Focal segmental glomerulosclerosis (FSGS) is a common cause of
      nephrotic syndrome. Although the pathogenesis is not known, recent studies
      suggest that FSGS may be a podocyte disease. The aim of this study was to look
      for podocyte injury in this disease, using measurements of urinary podocytes.
      METHODS: We examined the first morning urine of the day collected from 71
      patients (45 men and 26 women, median age and range 11.2 and 3-29 years)
      diagnosed as having nephrotic syndrome. Freshly voided urine samples were
      examined by immunofluorescence labeling using monoclonal antibodies against human
      podocalyxin. Renal histological examinations were performed in 58 of the 71
      patients: 28 had minimal-change disease, 20 had FSGS, and 10 had membranous
      nephropathy. RESULTS: Median and range of urinary podocytes measured were 0.2 and
      0-40.8 cells/ml for 71 patients with nephrotic syndrome and 0 and 0-0.8 cells/ml
      for normal healthy control subjects (n = 200). Patients with FSGS had
      significantly higher levels of urinary podocytes (median and range 1.3 and 0-40.8
      cells/ml) than those with minimal-change disease (median and range 0 and 0-6.9
      cells/m; p = 0.003) or membranous nephropathy (median and range 0 and 0-1.4
      cells/ml; p = 0.02). CONCLUSIONS: The urinary excretion of podocytes is
      significantly higher in patients with FSGS as compared with those having
      membranous nephropathy or minimal-change disease. These findings suggest that
      podocyte injury and loss in the urine may have an important role in the
      pathogenesis of FSGS.

PMID- 11598403
TI  - Erythropoietin and cardiocirculatory condition in aged patients with chronic
      renal failure.
AB  - BACKGROUND/AIM: The clearest benefit of recombinant human erythropoietin (rHuEPO)
      in end-stage renal disease is a substantial reduction in transfusion dependency
      and an improved quality of life. In this report, we describe the efficacy of
      weekly subcutaneous administration of rHuEPO in 11 elderly patients with anemia
      secondary to chronic renal failure. METHODS: The role of rHuEPO therapy in
      increasing the patient's quality of life and in decreasing the hospitalization
      rates secondary to cardiac morbidity was verified in 11 elderly patients (age
      range between 66 and 85 years) with anemia due to chronic renal failure. The mean
      hemoglobin level at the beginning of the study was 8.2 +/- (SD) 0.7 g/dl, and the
      serum creatinine concentration was 4.8 +/- 1.36 mg/dl. The patients underwent
      baseline and annual echocardiography, in addition to an electrocardiogram.
      RESULTS: Most patients experienced a partial regression of left ventricular
      hypertrophy, and no congestive heart failure was documented. The mean hemoglobin
      level during rHuEPO therapy increased to 11.3 +/- 1.2 g/dl, while the mean serum
      creatinine concentration did not change significantly. CONCLUSIONS: Our results
      confirm that early anemia correction in aged chronic renal failure patients
      permits improvement of the quality of life, of exercise performance, and of
      cognitive functions. Reduced transfusion need and regression of left ventricular
      hypertrophy favor a minor incidence of cardiac morbidity and contribute to reduce
      health costs.

PMID- 11598404
TI  - Pregnancy outcome in nephrotic syndrome with mixed connective tissue disease.
AB  - We describe two pregnancies of a young woman with mixed connective tissue
      disease. In June 1983, she was diagnosed as having Raynaud's phenomenon,
      arthralgia, and proteinuria. She then developed nephrotic syndrome.
      Methylprednisolone was initially prescribed at a large dose of 1 g/day which was
      slowly tapered to 5 mg/day. The proteinuria disappeared. During both pregnancies
      (the first beginning in December 1988 and the second in May 1992), the patient
      was placed on a prednisolone maintenance dose (5 mg/day). Both neonates were born
      healthy at term with no complications. Continuing prednisolone may be useful in
      pregnant women, and aggressive treatment to prevent mixed connective tissue
      disease exacerbation may be appropriate during pregnancy.

PMID- 11598405
TI  - Buerger's disease in a patient with minimal-change nephrotic syndrome.

PMID- 11598406
TI  - Hemolytic uremic syndrome associated with influenza A virus infection.

PMID- 11598407
TI  - Chylous ascites in an adult patient with nephrotic syndrome due to membranous
      nephropathy.

PMID- 11598408
TI  - Novel therapies in lung cancer management. An update on the role of topotecan.

PMID- 11598409
TI  - Current standards of care in small-cell and non-small-cell lung cancer.
AB  - Lung cancer is the leading cause of cancer-related death in the United States,
      accounting for over 30% of cancer deaths in men and 25% in women. Small-cell lung
      cancer (SCLC) and non-small-cell lung cancer (NSCLC) are uniformly aggressive
      tumors, with rates of regional or distant metastases at diagnosis as high as 70%.
      Because the majority of these tumors are unresectable, patients with relatively
      good performance status receive platinum-based chemotherapy. Although no
      treatment consensus exists, currently recommended regimens for SCLC include PE
      (cisplatin and etoposide), CAV (cyclophosphamide, doxorubicin, and vincristine),
      CAE (cyclophosphamide, doxorubicin, and etoposide), and CAVE (cyclophosphamide,
      doxorubicin, vincristine, and etoposide). Of these, the PE regimen has been
      widely accepted in the United States, although CE (carboplatin and etoposide)
      provides better tolerability. For NSCLC, standard chemotherapy regimens have
      included platinum-based therapy (cisplatin and a vinca alkaloid or PE). Data from
      recent studies suggest that the addition of paclitaxel to platinum modestly
      improves tumor response and survival in NSCLC. Although SCLC and NSCLC are both
      responsive to first-line chemotherapy, most patients relapse and die from their
      disease, with 5-year survival rates of approximately 15%. Given the disappointing
      survival rates associated with SCLC and NSCLC, the introduction of new cytotoxic
      agents has been eagerly anticipated. Evidence of improved response and extended
      survival is mounting for various combinations of established regimens (e.g., PE)
      with newer drugs exhibiting novel mechanisms of action and single-agent antitumor
      activity, such as gemcitabine, paclitaxel, docetaxel, vinorelbine, and topotecan.
      This article reviews the current standards of care in SCLC and NSCLC, and
      introduces the potential role of newer agents given in combination with standard
      chemotherapy.

PMID- 11598410
TI  - New advances in lung cancer chemotherapy: topotecan and the role of topoisomerase
      I inhibitors.
AB  - Objective tumor responses and survival rates with standard chemotherapy options
      for small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) have
      been disappointing. However, several promising new classes of agents have emerged
      in recent years, including the taxanes, mitotic spindle inhibitors,
      antimetabolites, and topoisomerase I and II inhibitors. The molecular target of
      several of these new agents is topoisomerase I, an enzyme that is essential for
      DNA replication and is up-regulated in tumor cells. Inhibition of this enzyme by
      drugs such as topotecan and irinotecan leads to cell death and is the basis for
      their anticancer activity. The process of DNA replication is halted by the
      covalent binding of the drug in a topoisomerase I drug/DNA ternary reaction
      intermediate. The pharmacokinetics of the approved regimen--a 30-min infusion
      daily for 5 days at 21-day intervals--are well defined, with proportional
      increases in the area under the plasma concentration-time curve, peak plasma
      concentration, and steady state concentration following application of higher
      doses. The antitumor activities of both the intravenous and oral formulations of
      topotecan have been tested in clinical trials. Topotecan is well tolerated and
      has demonstrated good efficacy in patients with relapsed SCLC when administered
      as monotherapy or in combination regimens as first-line or second-line therapy.
      Preliminary trials also indicate that topotecan is well tolerated and has
      activity in the first-line treatment of NSCLC. In this article an overview of new
      agents in lung cancer chemotherapy is provided, with particular attention paid to
      the topoisomerase I inhibitors. A review of topotecan--the first topoisomerase I
      inhibitor to be approved for second-line therapy in SCLC--is presented as an
      illustration of the promise these new agents hold for the treatment of SCLC and
      NSCLC.

PMID- 11598411
TI  - A phase I trial of a 5-day schedule of intravenous topotecan and etoposide in
      previously untreated patients with small-cell lung cancer.
AB  - A phase I dose-escalation study was undertaken to determine the maximum tolerated
      dose of the intravenous combination of topotecan and etoposide in previously
      untreated patients with small-cell lung cancer. Nineteen patients were treated
      with 30-min infusions of topotecan (0.5 mg/m(2)/day for cohort 1; 0.75
      mg/m(2)/day for cohort 2) followed by 1-hour infusions of a fixed daily dose of
      etoposide (60 mg/m(2)/day) for 5 consecutive days every 3 weeks. Patient cohort 1
      (n = 7) received a total of 41 courses of chemotherapy. Grade 4 neutropenia
      occurred after 17% of the courses of therapy, and there was 1 episode of dose
      limiting toxicity in this patient cohort. In patient cohort 2 (n = 12), a total
      of 64 courses of chemotherapy were administered. Grade 3 or 4 neutropenia
      occurred following 41 and 37% of the courses of therapy, respectively. Grade 3
      thrombocytopenia occurred following 19% of the courses of therapy, and there were
      3 episodes of dose-limiting toxicity in this patient cohort. There were no toxic
      deaths, and all nonhematologic toxicity (except hair loss) was </= grade 2. No
      further dose escalation was performed because of the degree of myelosuppression
      seen in patient cohort 2. All 19 patients were evaluable for response. Eighteen
      (95%) patients responded (14 partial responses and 4 complete responses) and the
      median survival was 10 months. This 5-day schedule of intravenous topotecan and
      etoposide administered sequentially on the same day is well tolerated, and the
      preliminary response rates were high in patients with previously untreated small
      cell lung cancer.

PMID- 11598412
TI  - Feasibility of oral topotecan plus intravenous paclitaxel in advanced non-small
      cell lung cancer.
AB  - Standard chemotherapy regimens in non-small-cell lung cancer (NSCLC) are platinum
      based (cisplatin, carboplatin), with inherent, well-known antitumor activity and
      toxicity. However, the availability of new agents with novel mechanisms of action
      and activity in a range of tumor types, coupled with suboptimal activity of
      single-agent therapy, have prompted the investigation of multidrug regimens in
      the treatment of NSCLC. One potential combination regimen, in which each agent
      has antitumor activity in NSCLC monotherapy, is topotecan plus paclitaxel. This
      article will review the feasibility and tolerability of an oral formulation of
      topotecan (1.0-1.5 mg/m(2)/day x 5 days) administered with intravenous paclitaxel
      (175 mg/m(2) as a 3-hour infusion on day 1) in advanced NSCLC patients. The
      maximum tolerated dose of oral topotecan will be reported, along with preliminary
      response and tolerability data.

PMID- 11598413
TI  - Is cisplatin required for the treatment of non-small-cell lung cancer? Experience
      and preliminary results of a phase I/II trial with topotecan and vinorelbine.
AB  - Platinum-based chemotherapy is considered standard treatment for advanced non
      small-cell lung cancer (NSCLC). However, toxicity of most platinum-based regimens
      is substantial and requires close monitoring and supportive care. Over the past
      decade, paclitaxel, docetaxel, vinorelbine, gemcitabine, irinotecan, and
      topotecan have been introduced into the clinic. These newer agents have shown
      promising activity against NSCLC with a favorable toxicity profile as single
      agents. For patients with metastatic NSCLC, palliation is the main goal of
      therapy. Therefore, treatment should be easy to administer on an outpatient
      basis. We explored a novel combination therapy avoiding platinum. Patients with
      recurrent or metastatic NSCLC were treated with intravenous (i.v.) topotecan (0.5
      1.0 mg/m(2)/day x 5) and i.v. vinorelbine (20-30 mg/m(2)/day on day 1 and day 5)
      in 21-day cycles. Dose-limiting toxicity (DLT) was defined separately with or
      without the addition of granulocyte colony-stimulating factor (G-CSF) support.
      Twenty-nine patients have been enrolled to date. At i.v. topotecan doses of 0.75
      1.0 mg/m(2)/day and i.v. vinorelbine of 25 mg/m(2)/day, neutropenia was frequent
      but of short duration (<7 days). The DLT of i.v. topotecan (0.85 mg/m(2)) in the
      absence of G-CSF support was based on myelosuppression with neutropenic fever.
      With the addition of G-CSF, a DLT has not been reached. Nonhematologic toxicities
      included mild to moderate fatigue and constipation. An overall clinical response
      rate of 42% was achieved, with responses noted at all dose levels. At a short
      median follow-up of 15 months, the median survival for all patients is 13 months.
      In conclusion, the combination regimen of topotecan and vinorelbine is feasible
      for outpatient administration and is well tolerated with less toxicity than
      platinum-based regimens. Preliminary response data demonstrate good tumor
      activity, suggesting that this regimen could make an excellent palliative
      treatment for advanced NSCLC.

PMID- 11598414
TI  - Feasibility of oral topotecan in previously untreated patients with small-cell
      lung cancer ineligible for standard therapy.
AB  - The single-agent activity of intravenous (i.v.) topotecan has been established in
      small-cell lung cancer (SCLC), with overall tumor responses of 39% in previously
      untreated patients and 11-37% in relapsed patients. An oral formulation of
      topotecan has been developed that is more convenient for patients, which may lead
      to greater compliance and greater prescribing flexibility for use in combination
      with other active agents. We initiated a phase II trial to test the feasibility
      of oral topotecan administered at 2.0 mg/m(2) on days 1-5 of a 21-day cycle in
      previously untreated SCLC patients. Patients received a median of 5 courses of
      oral topotecan. Grade 3/4 myelosuppression was common in patients treated with
      2.0 mg/m(2); secondary to 2 patients developing fatal sepsis, patients enrolled
      later in the study were treated at 1.7 mg/m(2). At both doses, the majority of
      nonhematologic toxicity was grade 1/2 in severity, and there were no
      discontinuations attributed to nonhematologic toxicity. In a patient population
      reflective of the general SCLC population (i.e. elderly with multiple
      comorbidities), oral topotecan was generally well tolerated at the lower dose
      level, with a preliminary antitumor activity profile comparable to i.v.
      topotecan. Clinical studies are currently under way to compare the antitumor
      activity of oral topotecan with i.v. topotecan in second-line SCLC and
      investigate oral topotecan in combination with other active agents in SCLC.

PMID- 11598415
TI  - Preliminary results of combined therapy with topotecan and carboplatin in
      advanced non-small-cell lung cancer.
AB  - Topotecan is a topoisomerase I inhibitor and an analogue of camptothecin with
      demonstrated activity in small-cell lung cancer. However, less is known about the
      potential role of topotecan in advanced non-small-cell lung cancer (NSCLC).
      Platinum-based combination therapy is currently recommended in NSCLC patients
      presenting with good performance status. Because topotecan demonstrates a novel
      mechanism of action, its investigation in platinum combinations is warranted. In
      phase I/II trials of topotecan given as part of a cisplatin-based regimen,
      significant antitumor activity has been observed, providing the rationale for
      conducting further studies aimed at assessing survival benefit. However, this
      combination exhibits sequence dependence, with increasing hematologic toxicity
      observed when cisplatin is administered on day 1 of a 5-day topotecan course.
      Cisplatin has been associated with dose-limiting nonhematologic toxicities.
      Carboplatin exhibits a different toxicity profile compared with cisplatin, which
      makes it an attractive agent to study in combination. A hypothesis can be made
      that carboplatin in combination with newer agents such as topotecan might compare
      favorably with classic cisplatin-based regimens, particularly with respect to
      efficacy:toxicity ratio. Therefore, a phase II study was initiated to determine
      the efficacy, toxicity, and safety of carboplatin-topotecan combination in
      advanced NSCLC. Preliminary results reported here show that topotecan with
      carboplatin is generally well tolerated with manageable hematologic toxicity.
      Indirect comparison with cisplatin-topotecan combination suggests a lower
      incidence of dose-limiting nonhematologic toxicity. Whether or not the
      carboplatin-topotecan regimen is able to offer tumor response and survival
      benefit comparable to those observed with cisplatin-based combinations remains to
      be established.

PMID- 11598416
TI  - Future role of topotecan in the treatment of lung cancer.
AB  - Topotecan (HYCAMTIN; GlaxoSmithKline, Brentford, Middlesex, UK) is a novel
      topoisomerase I inhibitor with potentially broad applicability in the treatment
      of solid and hematologic malignancies. In addition to its use in relapsed small
      cell lung cancer (SCLC), topotecan is under investigation in numerous studies for
      first-line therapy in SCLC and for first- and second-line treatment of non-small
      cell lung cancer (NSCLC). Preliminary evidence presented in this supplement
      demonstrates that single-agent topotecan and topotecan-based combination regimens
      are active in these settings. In addition to its potential use in SCLC and NSCLC,
      the feasibility and antitumor activity of topotecan as single-agent therapy and
      in combination therapy are under active investigation in a variety of other solid
      and hematologic tumors. Other important avenues of investigation include the
      feasibility and tumor activity of a more convenient oral formulation, as well as
      the investigation of alternate regimens (e.g., 3-day, weekly), with high priority
      given to regimen toxicity, patient convenience, and quality of life. Preliminary
      results of some of these trials are presented in this summary. The results of
      other clinical experience trials are eagerly anticipated.

PMID- 11598417
TI  - Enhanced relaxation to the rho-kinase inhibitor Y-27632 in mesenteric arteries
      from mineralocorticoid hypertensive rats.
AB  - Increased vasoconstriction is characteristic of hypertension. In this study, we
      tested the hypothesis that changes in vascular responses during mineralocorticoid
      hypertension may be due to increased activation of the Rho/Rho-kinase pathway. To
      test this, relaxation responses to the Rho-kinase inhibitor Y-27632 were
      determined by measuring isometric force in deendothelialized mesenteric arteries
      from mineralocorticoid-hypertensive rats and sham-operated controls. Following
      agonist-induced contraction by serotonin (5-HT, 5-hydroxytryptamine), arteries
      from hypertensive rats demonstrated a greater relaxation to the Rho-kinase
      inhibitor Y-27632 (65 +/- 5% vs. 28 +/- 10%). Treatment with an EC50
      concentration of Y-27632 following a KCl-induced contraction caused minimal
      relaxation of arteries in both groups of animals. These findings suggest that
      augmented Rho-kinase activity in the vasculature of mineralocorticoid
      hypertensive rats may contribute to the enhanced vascular reactivity of agonist
      mediated stimuli characteristic of this model of hypertension.

PMID- 11598418
TI  - Effects of nicorandil administration on survival rate and arrhythmias during
      reperfusion in anesthetized rabbits.
AB  - The aim was to study the effects of nicorandil (an ATP-sensitive K+ channel
      opener) and tolbutamide (an ATP-sensitive K+ channel blocker) on reperfusion
      induced arrhythmias in pentobarbitone and ketamine anesthetized rabbits.
      Arrhythmias were induced by reperfusion for 20 min following a 15-min ligation of
      the left main coronary artery with a silk ligature. Rabbits were pretreated with
      nicorandil (0.47, 0.93 or 1.86 mg/kg i.v.) or tolbutamide (180 mg/kg i.p.) or
      vehicle (dimethylsulfoxide/saline) before the coronary artery occlusion. In the
      control group (n = 10), only 60% of the animals survived during reperfusion.
      Intravenous pretreatment with 0.47, 0.93 or 1.86 mg/kg of nicorandil increased
      the survival rate to 86% (n = 7), 75% (n = 8) and 86% (n = 7), respectively.
      Nicorandil pretreatment significantly decreased the incidence and duration of
      reperfusion-induced life-threatening arrhythmias and increased the number of
      animals that survived without developing any arrhythmia. Tolbutamide pretreatment
      was associated with a decreased survival rate of 50% (n = 12) and an increase in
      the incidence and duration of reperfusion-induced arrhythmias. Pretreatment with
      nicorandil may result in protection against reperfusion-induced arrhythmias and
      increased survival in anesthetized rabbits.

PMID- 11598419
TI  - Neuromuscular blocking effects of the aminoglycoside antibiotics arbekacin,
      astromicin, isepamicin and netilmicin on the diaphragm and limb muscles in the
      rabbit.
AB  - Aminoglycoside antibiotics are known to produce a depression of neuromuscular
      function which may cause prolonged paralysis of respiratory muscles. However,
      differences in the effects of aminoglycoside antibiotics on diaphragm and limb
      muscles have not been investigated. We determined the neuromuscular blocking
      effects of the aminoglycoside antibiotics arbekacin sulfate, astromicin sulfate,
      isepamicin sulfate and netilmicin sulfate on the diaphragm, tibialis anterior and
      soleus muscles in anesthetized rabbit nerve-muscle preparations. Neuromuscular
      block was assessed by mechanical response with single twitch stimulation.
      Cumulative drug dose-response curves were obtained for three different muscles in
      24 rabbits. The mean ED(50) and ED(95) of the antibiotics in diaphragm, tibialis
      anterior and soleus muscles were calculated. The neuromuscular blocking effects
      of all the aminoglycosides on ED(50) and ED(95) values were in the order of
      soleus > tibialis anterior > diaphragm, and soleus > diaphragm > tibialis
      anterior, respectively. The ED(50) ratios for the tibialis anterior and soleus
      muscles were approximately 1.5 and 2.7 times greater than that for the diaphragm.

PMID- 11598420
TI  - Availability of learned helplessness test as a model of depression compared to a
      forced swimming test in rats.
AB  - This study was designed to evaluate the antidepressant activity of various
      antidepressants using the learned helplessness test (LH) or the forced swimming
      test (FS) in rats. Repeated treatment of the tricyclic antidepressants imipramine
      (10 mg/kg, p.o.), clomipramine (0.625 mg/kg, p.o.), amitriptyline (10 mg/kg,
      p.o.) and amoxapine (20 mg/kg, p.o.) reduced the number of escape failures in the
      LH group, respectively. Repeated treatment of an atypical antidepressant,
      mianserin (2.5 and 5 mg/kg, p.o.), and one of the selective serotonin reuptake
      inhibitors (SSRI), fluvoxamine (1.25 mg/kg, p.o.), also reduced the number of
      escape failures in the LH group. In the FS, repeated treatment of imipramine (5,
      10 mg/kg, p.o.), amitriptyline (5, 10 mg/kg, p.o.) and mianserin (10 mg/kg)
      significantly decreased the duration of immobility time. On the other hand,
      repeated treatment of amoxapine (5-20 mg/kg), clomipramine (0.1325-1.25 mg/kg,
      p.o.) and fluvoxamine (0.3125-1.25 mg/kg, p.o.) failed to decrease the duration
      of immobility time in the FS group. In conclusion, these results suggest that the
      LH group is sensitive to agents with a variety of antidepressant properties
      compared to the FS group in rats.

PMID- 11598422
TI  - Oral self-administration of ethanol and cocaine in rats.
AB  - Most laboratory animal studies on self-administration of drugs of abuse use only
      one drug, whereas humans frequently engage in polydrug use. For this reason, we
      studied oral self-administration of ethanol (E) and cocaine (C) with the free
      choice bottle method using a single drug alone, a combination (E and C in
      separate bottles) or a mixture of both drugs in a single bottle. Young female
      rats (45 days) consumed similar amounts of C if offered alone (12.4 +/- 7.5
      mg/kg/day), in the presence of ethanol (10.6 +/- 3.5) or as E/C mixture (8.0 +/-
      4.0). They also consumed similar amounts of E if offered alone (3.8 +/- 1.6
      ml/kg/day), in the presence of C (2.3 +/- 0.8) or E/C mixture (2.4 +/- 1.1).
      Voluntary consumption of both drugs varied markedly among animals but was
      consistent in a given rat. No correlation occurred between consumption of E and
      C. Young male rats behaved similarly and consumed similar amounts of E and C
      alone, in combination and as mixture. While E consumption was similar, C
      consumption was higher in female rats. Old male rats (180 days) were similar to
      young male rats. The presence of a saccharin solution as a distracter had no
      effect on intake of E or C in young females but reduced E intake only in young
      male rats. In young animals, prior voluntary consumption of either E or C had no
      effect on subsequent voluntary consumption of the same or other drug offered in
      combination. These results indicate that this model may be useful to study
      polydrug use in humans, that consumption of both E and C is strongly controlled
      by an individual animal, that prior exposure to one drug had no or little effect
      on a subsequent consumption of the same or other drug in combination and that
      intake of E or C seems to be independent of each other suggesting two independent
      reward centers.

PMID- 11598421
TI  - Evaluation of the effects of nicorandil on experimentally induced gastric ulcers.
AB  - The present study was designed to evaluate the effects of a potassium channel
      opener, nicorandil, and to elucidate its possible mechanism of action in aspirin
      plus pylorus ligation induced and ethanol-induced gastric ulcers in rats. In an
      attempt to ascertain the involvement of K(ATP) channels in the modulation of
      gastric ulcers, the effects of nicorandil alone as well as in the presence of the
      K(ATP) channel blocker glibenclamide were studied. Nicorandil and glibenclamide
      were administered orally at a dose of 2 mg/kg throughout the study. Nicorandil
      showed significant protection in all the selected models that was evident from a
      significant reduction in the ulcer index. The results of nicorandil treatment
      were comparable with those of cimetidine treatment in both models. Glibenclamide
      was found to inhibit this effect of nicorandil. Further, glibenclamide showed
      proulcerogenic potential in ethanol and aspirin plus pylorus ligation models. In
      the aspirin plus pylorus ligation model, nicorandil showed a significant
      reduction in total acidity, pepsin activity, and protein content and a
      significant rise in mucin activity. The effect of nicorandil was also studied on
      gastric mucosal blood flow (GMBF). The GMBF was found to be more increased in the
      test group than in the control group, indicating enhancement of GMBF by
      nicorandil. Glibenclamide reversed this effect of nicorandil as well. It is
      concluded from our study that nicorandil possesses antiulcer activity in the
      models employed in the present study. This may be attributed to the opening of
      K(ATP) channels, inhibition of acid secretion, enhancement of mucin activity, and
      improvement in GMBF.

PMID- 11598423
TI  - Effects of adenosine on thrombosis and thrombolysis in a canine experimental
      preparation.
AB  - Intracoronary infusion of adenosine is reported to inhibit cyclic flow variations
      after coronary artery injury and stenosis. This study was performed in the
      anesthetized dog to determine if adenosine prevents arterial thrombosis and/or
      reocclusion after thrombolysis. Carotid and coronary arteries were instrumented
      with Doppler(TM) flow probes, a critical stenosis, infusion line and an anodal
      electrode. Two protocols were employed. In the thrombosis protocol, intracarotid
      infusion of adenosine (20 microg/kg/min for 3 h) did not alter cyclic flow
      variations or patency during induction of vessel wall injury. In the second
      protocol, occlusive arterial thrombi were induced by anodal current injury and
      lysed with local application of tissue plasminogen activator. Whereas adenosine
      prolonged the time to arterial occlusion, it did not affect cyclic flow
      variations or time to reocclusion after thrombolysis.

PMID- 11598424
TI  - The inhibitory mechanism of rebamipide on the mediator release in the guinea pig
      lung mast cells activated with specific antigen-antibody reactions.
AB  - This study aim was to assess the effects of rebamipide on the mechanism of
      histamine release and biosynthesis and release of leukotrienes caused by mast
      cell activation. We purified mast cells from guinea pig lung tissues by the use
      of enzyme digestion, the rough and the discontinuous density percoll gradient
      method. Mast cells were sensitized with IgG1 (anti-OVA) antibody and challenged
      with ovalbumin. Mast cells were also stimulated with A23187 and the intracellular
      Ca(2+) level was measured. Histamine and leukotrienes were measured by automated
      fluorometric analyzer and radioimmunoassay, respectively. The intracellular
      Ca(2+) level was analyzed using a confocal laser scanning microscope. Protein
      kinase C (PKC) activity was determined by protein phosphorylated with [gamma
      (32)P]ATP. The phospholipase D activity was assessed by the labeled
      phosphatidylalcohol. Mass 1,2-diacylglycerol (DAG) was measured by the [(3)H]DAG
      produced when prelabeled with [(3)H]myristic acid. PLA(2) activity was determined
      by measuring the arachidonic acid released from the labeled phospholipids.
      Rebamipide decreased the releases of histamine and leukotrienes, and completely
      blocked Ca(2+) influx during mast cell activation by antigen-antibody reactions.
      It also decreased the release of histamine and leukotrienes during mast cell
      activation by A23187. The PKC and PLD activities were also decreased by
      rebamipide in a dose-dependent manner. Rebamipide inhibited the mass DAG
      production and PLA(2) activity during mast cell activation. The data suggest that
      rebamipide inhibits intracellular signals and blocks Ca(2+) influx in mast cells
      activated by specific antigen-antibody reactions, which in turn inhibits
      histamine release and leukotriene generation.

PMID- 11598425
TI  - Muscarinic receptor subtypes mediating vasorelaxation of the perforating branch
      of the human internal mammary artery.
AB  - The effect of acetylcholine (ACh) on the isolated perforating branch of the human
      internal mammary artery (HIMA) was investigated. ACh induced concentration- and
      endothelium-dependent relaxation of arterial rings precontracted with
      phenylephrine (pEC(50) = 6.93 +/- 0.01). The muscarinic receptor antagonist
      atropine (no selectivity), pirenzepine (M(1)), methoctramine (M(2)), and p-fluoro
      hexahydro-siladifenidol (M(1)/M(3)) competitively antagonized the response to
      ACh. The pA(2) values were 9.81 +/- 0.15, 7.74 +/- 0.08, 6.27 +/- 0.08, and 7.88
      +/- 0.04, respectively. In conclusion, this study has shown that ACh induced an
      endothelium-dependent relaxation of the perforating branch of the HIMA by
      stimulation of muscarinic receptors on the endothelial cells. On the basis of
      differential antagonist affinity, we suggest that the muscarinic receptors
      involved in the ACh-induced relaxation of the isolated perforating branch of HIMA
      are predominantly of M(1) subtype.

PMID- 11598426
TI  - Thapsigargin-induced calcium entry and apoptotic death of neutrophils are blocked
      by activation of protein kinase C.
AB  - Intracellular free calcium ([Ca(2+)](i)) concentration, free oxygen radical (FOR)
      production, DNA breakdown, and plasma membrane phosphorylation were studied in
      human neutrophils activated with thapsigargin and phorbol myrisate acetate (PMA).
      Thapsigargin produced a rapid and sustained rise of [Ca(2+)](i), activated the
      endonuclease, and caused the breakdown of the neutrophil's DNA with a half-time
      close to 6 h. The protein kinase C activator PMA failed to inhibit the initial
      rise of [Ca(2+)](i), but inhibited the second phase of thapsigargin-induced
      calcium transient and completely blocked the activation of the endonuclease
      induced by thapsigargin. Thapsigargin induced a minor and delayed production of
      FOR, whereas PMA caused an abrupt and sustained FOR production that was enhanced
      by thapsigargin. Two plasma membrane proteins close to 50 and 64 kD were
      phosphorylated in PMA-activated neutrophils. These results suggest that the
      nonphosphorylated form of the membrane protein permits basal and thapsigargin
      induced calcium entry. Phosphorylation by PMA of plasma membrane protein inhibits
      calcium uptake in both resting and thapsigargin-activated neutrophils and
      contributes to the block of the activation of the apoptotic endonuclease.

PMID- 11598427
TI  - Which are the leading countries in clinical medicine research? A citation
      analysis (1981-1998).

PMID- 11598428
TI  - A randomized controlled trial of cognitive therapy versus intensive behavior
      therapy in obsessive compulsive disorder.
AB  - BACKGROUND: The study was designed to compare cognitive therapy (CT) with
      intensive behavior therapy (BT) in obsessive-compulsive disorder (OCD) and to
      study their change process. METHODS: Sixty-five outpatients with DSM-4 OCD were
      randomized into 2 groups for 16 weeks of individual treatment in 3 centers. Group
      1 received 20 sessions of CT. Group 2 received a BT program of 20 h in two
      phases: 4 weeks of intensive treatment (16 h), and 12 weeks of maintenance
      sessions (4 h). No medication was prescribed. RESULTS: Sixty-two patients were
      evaluated at week 4, 60 at week 16 (post-test), 53 at week 26 and 48 at week 52
      (follow-up). The response rate was similar in the 2 groups. The Beck Depression
      Inventory (BDI) was significantly more improved by CT (p = 0.001) at week 16. The
      baseline BDI and Obsessive Thoughts Checklist scores predicted a therapeutic
      response in CT, while the baseline BDI score predicted a response in BT. At week
      16, only the changes in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and a
      scale measuring the interpretation of intrusive thoughts correlated in CT, while
      the changes in Y-BOCS, BDI, and interpretation of intrusive thoughts correlated
      in BT. Improvement was retained at follow-up without a between-group difference.
      The intent-to-treat analysis (last observation carried forward) found no between
      group differences on obsessions, rituals and depression. CONCLUSIONS: CT and BT
      were equally effective on OCD, but at post-test CT had specific effects on
      depression which were stronger than those of BT. Pathways to improvement may be
      different in CT and BT. The outcomes are discussed in the light of an effect size
      analysis.

PMID- 11598429
TI  - Fluoxetine and fluvoxamine combined with individual cognitive-behaviour therapy
      in binge eating disorder: a one-year follow-up study.
AB  - BACKGROUND: : The treatment of binge eating disorder (BED) is still the object of
      debate. In the present study, the effectiveness of antidepressant drugs
      (fluoxetine - FLX - 60 mg/day, fluvoxamine - FLV -300 mg/day), cognitive
      behavioural therapy (CBT) and combined treatments (CBT + FLX, CBT + FLV) has been
      evaluated in a randomized, clinical trial. Results at the end of the active
      treatment (in the 24th week) and 1-year follow-up outcomes have been evaluated.
      METHODS: One hundred eight (44 M, 64 F) BED patients were randomly assigned to
      either CBT, FLX (60 mg/day), FLV (300 mg/day), CBT + FLX or CBT + FLV, for 24
      weeks. At the beginning (T0), at the end (T1) of treatment and after 1 year (T2),
      body mass index (BMI) and eating attitude and behaviours (by EDE 12.0D) were
      assessed. RESULTS: At T1, BMI and EDE scores were significantly reduced in CBT,
      CBT + FLX and CBT + FLV, but not in the FLX and FLV treatment groups. In the CBT
      + FLV group, a greater (p < 0.05) reduction of EDE total scores was observed,
      when compared to CBT + FLX or CBT treatment groups. At T2, BMI was significantly
      higher than at T1, but still significantly lower than at T0 in the CBT, CBT + FLX
      and CBT + FLV groups, while EDE scores remained unchanged from T1 in all
      treatment groups. CONCLUSIONS: CBT was more effective than FLX or FLV in the
      treatment of BED. The addition of FLX to CBT does not seem to provide any clear
      advantage, while the addition of FLV could enhance the effects of CBT on eating
      behaviours. Modifications of eating behaviours are maintained at the 1-year
      follow-up, although the lost weight was partly regained.

PMID- 11598430
TI  - An exploratory study into the effect of group psychotherapy on cardiovascular and
      immunoreactivity to acute stress in breast cancer patients.
AB  - BACKGROUND: : Previous studies of cancer patients investigated the effect of
      psychological treatment on basal endocrine and immune values. Using a randomized
      experiment, we explored the effect of a 13-week experiential-existential group
      psychotherapy (EEGP) program on the reactivity to a speech task in breast cancer
      patients. We explored whether changes in cardiovascular and immune reactivity to
      a speech task over the 3-month period correlated with changes in psychological
      distress and emotional expression. METHODS: Patients who had been treated for
      early-stage breast cancer and who were diagnosed as having either positive
      axillary lymph nodes or distant metastases were randomly assigned to either EEGP
      or a waiting list control (WLC) condition. We continuously recorded heart rate
      (HR), diastolic (DBP) and systolic blood pressure (SBP) in response to the speech
      task before and after treatment. We also measured lymphocyte proliferation to
      pokeweed (PWM) and phytohemagglutinin (PHA), and natural killer cell activity
      (NKCA) as well as peripheral blood lymphocyte distributions in blood samples that
      were drawn before, during and after the speech task. RESULTS: Patients in EEGP
      had smaller increases in natural killer (NK) cells induced by the speech task
      after treatment versus task-induced values observed at study entry and greater
      than pre-/posttreatment changes seen in patients randomized to the WLC. A similar
      pattern emerged with respect to NKCA over the intervention period, which was
      independent of the changes in NK cells. There were no differences between
      patients assigned to EEGP and WLC in HR, DBP and SBP responses as well as in
      changes in PWM- and PHA-induced lymphocyte proliferation in response to the
      speech task measured before and after the 3-month intervention period. Individual
      differences in pre-/posttreatment increases in emotional expression but not in
      psychological distress were significantly associated with smaller changes in the
      number and function of NK cells over the 3-month period. CONCLUSIONS: These
      findings may indicate that emotional expression during EEGP may render breast
      cancer patients more comfortable expressing their emotional responses to the
      speech challenge, which, in turn, results in smaller stress-induced changes in NK
      cells and function.

PMID- 11598431
TI  - Intellect and somatic health: associations with hypochondriacal concerns,
      perceived threat and fainting.
AB  - BACKGROUND: : Compared to the other domains of the Big 5, intellect has been
      relatively underresearched with regard to somatic health outcomes. It is argued
      that this, in part, is because specific hypotheses concerning intellect and
      somatic health have not been formulated. It is argued that intellect is related
      to both alexithymia and hypnotic ability. As such the High Risk Model of Threat
      Perception forms one useful theoretical framework for generating hypotheses about
      intellect and somatic health. On this basis it is hypothesised that intellect
      should show a U-shaped relationship to hypochondriacal concerns, a positive
      association with appraisals of threat and loss, and a negative association with
      levels of self-reported vasovagal syncope (feelings of faintness). METHODS: Two
      cross-sectional studies, using student samples (n = 205, 179), examined the
      relationships between intellect and hypochondriacal concerns as well as intellect
      and appraisals of threat and loss. A third prospective study, using a sample of
      blood donors (n = 373), examined the relationship between levels of self-reported
      vasovagal syncope and intellect. RESULTS: Compared to the other domains of the
      Big 5, intellect demonstrated a U-shaped association with hypochondriacal
      concerns, a positive association with perceived threat and loss and a negative
      association with fainting. The negative association with fainting remained once
      incidence of previous fainting, the number of previous blood donations and
      emotional stability were held as covariates. CONCLUSIONS: Intellect is associated
      in a number of important ways with a variety of psychosomatic variables.

PMID- 11598434
TI  - Stem cells in the epidermis.
AB  - The epidermis consists of three actively proliferating units, the interfollicular
      epidermis, the hair follicle, and the sebaceous gland. Stem cells in the
      epidermis have the capacity to produce all three of these units. The fate of the
      epidermal stem cells and some of their progeny can be altered, dependent on the
      environment in which they reside and the genes they express. In this review, we
      describe the major experiments that have contributed to the understanding of the
      epidermal stem cells and the control of their fate.

PMID- 11598432
TI  - Effects of client-centered psychotherapy for personality disorders alone and in
      combination with psychopharmacological treatment. An empirical follow-up study.
AB  - BACKGROUND: : There is an increasing interest concerning the treatment of
      patients with personality disorders (PD) in data on the efficacy of
      psychotherapeutic strategies especially when combined with medication. METHODS:
      The efficacy of an inpatient client-centered treatment program (CCT) was studied
      prospectively in 142 patients with PD and additional depressive, anxiety or
      eating disorders (ICD-10). RESULTS: Significant improvements in depression, self
      esteem and social adjustment were achieved up to discharge, which remained stable
      at the 1-year follow-up. The efficacy with regard to individual variables or the
      total result could not be further enhanced by a combination with
      psychopharmacological treatment (CCT + MED), consisting mainly of
      antidepressants. Within the subgroups of patients with socially deviant (F60.0
      2), emotionally unstable/borderline (F60.3) and histrionic/narcissistic PD
      (F60.4, F60.8), CCT was significantly superior to CCT + MED in the reduction of
      depression (Bech-Rafaelsen Melancholia Scale ratings), whereas the response was
      enhanced by medication in the subgroup of patients with socially dependent
      'cluster C' PD (F60.5-7). CONCLUSIONS: The results are discussed with regard to
      client-centered therapeutic concepts and to the further development of
      differential combination strategies.

PMID- 11598435
TI  - Chemoprevention of basal cell carcinomas in the ptc1+/- mouse--green and black
      tea.
AB  - Skin cancers are a rising menace as their incidence increases, attributed in part
      to increasing ultraviolet radiation exposure. This increasing problem has
      stimulated efforts to devise useful preventive approaches. The uncertain efficacy
      of exhortations to avoid sun exposure and to use protective clothing and
      sunscreens to reduce damage when exposed argue for the development of an oral
      chemopreventive agent. Bickers and others have studied the effects and mechanisms
      of tea and of its putative active components on inhibition of skin cancer in
      experimental models. To continue this work, we have studied the effects of oral
      green tea and black tea on a new model of ultraviolet-induced skin carcinogenesis
      - the development of basal cell carcinomas in ptc1+/- mice. To our surprise, we
      have found that tea preparations which others have used to prevent squamous cell
      carcinoma formation in mice fail to inhibit basal cell carcinogenesis in our
      model, suggesting that prevention of this cancer may require special, tumor
      specific approaches.

PMID- 11598436
TI  - Cutaneous vitamins A and E in the context of ultraviolet- or chemically-induced
      oxidative stress.
AB  - Vitamins A and E are present in mammalian skin. Although the main circulating
      form of vitamin A in the blood is retinol, the epidermis stores it as retinyl
      esters. The epidermis can be easily loaded with high amounts of vitamin A by
      topical application of either retinol or retinaldehyde, two well-tolerated
      precursors of the biologically active retinoic acid, while topical alpha
      tocopherol loads the epidermis with vitamin E. The probable physiological
      function of epidermal vitamin E is to contribute to the antioxidant defense of
      the skin, whereas that of epidermal vitamin A (retinol and retinyl esters) is not
      yet well understood. Besides being a precursor for retinoic acid, vitamin A also
      has a free radical scavenging potential. Due to their physical properties,
      vitamins A and E absorb ultraviolet (UV) light in the region of solar spectrum
      that is responsible for most of the deleterious biological effects of the sun. In
      the mouse, topical vitamin A has been shown to prevent the UV-induced epidermal
      hypovitaminosis A, while topical vitamin E prevents oxidative stress and
      cutaneous and systemic immunosuppression elicited by UV. Thus constitutive
      epidermal vitamins A and E appear complementary in preventing UV-induced
      deleterious cutaneous and systemic effects, and these properties can be
      reinforced by topical application of retinol or retinaldehyde and topical alpha
      tocopherol.

PMID- 11598437
TI  - Chemoprevention of skin cancer through natural agents.
AB  - To reduce the occurrence of skin cancers, the use of sunscreens and wearing
      protective clothing while in the sun are emphasized. These are important
      strategies, but sadly these efforts are only partially effective. Thus, the
      development of novel strategies to reduce the occurrence of skin cancer is a
      highly desirable goal. One attractive approach is through chemoprevention which
      is the use of naturally occurring agents or synthetic compounds to prevent the
      occurrence and subsequent development of cancer. The ideal chemopreventive
      agent(s) for use for prevention of skin cancer must be available in its active
      form with none or minimal toxicity and a known mechanism of action. A wide range
      of synthetic and naturally occurring agents have been identified as a rich source
      of skin cancer chemopreventive agents. For a variety of reasons, there is a
      greater emphasis on the use of naturally occurring compounds for skin cancer
      chemoprevention, and many such agents have found a place in skin care products.
      This review focuses on the use of naturally occurring agents present in the diet
      and beverages consumed by humans for the chemoprevention of skin cancer.

PMID- 11598438
TI  - Host defense mechanisms in polyaromatic hydrocarbon carcinogenesis.
AB  - Polyaromatic hydrocarbons (PAHs) are chemicals that are widely employed to
      examine the complex mechanisms by which chemicals cause cancer. While it is clear
      that the tumors that carcinogenic PAHs produce elicit an immune response, the
      interplay between host immune defense mechanisms and earlier stages in the
      cutaneous carcinogenesis pathway has received little attention. Studies from our
      laboratories have shown that topical application of several different PAHs to
      mice results in the development of an antigen-specific cell-mediated immune
      response to them. The response is genetically determined and is mediated by CD8+
      T cells. Development of a cell-mediated immune response is associated with
      resistance to dimethylbenz(a)anthracene tumorigenesis. These findings are
      consistent with the hypothesis that host defense mechanisms against PAHs help to
      protect individuals from the carcinogenic actions of these agents. This may form
      the basis for novel immunopreventive strategies for individuals at high risk for
      development of tumors produced by PAHs.

PMID- 11598439
TI  - Diagnosis and treatment of the acute porphyrias: an interdisciplinary challenge.
AB  - The porphyrias comprise a group of fascinating disorders resulting from
      predominantly inherited as well as acquired deficiencies of one of the eight
      enzymes along the pathway of heme biosynthesis. On the basis of clinical aspects,
      the different types of porphyrias can be classified in acute and non-acute forms.
      However, an exact classification is often difficult since the porphyrias might
      reveal unspecific clinical symptoms and/or overlapping biochemical features. In
      particular, this is true for the acute porphyrias which can present with life
      threatening acute neurovisceral attacks that require immediate medical
      intervention. Due to the multiple facets of these disorders, the diagnosis and
      treatment of the acute porphyrias should always imply a close interdisciplinary
      collaboration to serve patients and their families most effectively.

PMID- 11598440
TI  - New developments in photoprotection of human skin.
AB  - Because of increased leasure time, the growing popularity of staying outdoors and
      of holidays in the sun, it has become more and more important to study the
      molecular and photobiological effects that ultraviolet (UV) radiation exerts on
      human skin. Information obtained from these studies is being used to constantly
      improve the quality of sunscreen preparations containing organic and inorganic
      filters. It is also fostering the development of antioxidants and active agents
      that can be used in combination with or in addition to UV filters to provide
      better photoprotection for human skin. In addition, these studies provide novel
      test models which allow to prove or disprove the efficacy of a given sunscreen
      preparation for biological endpoints that differ from the sunburn reaction and
      are of direct relevance for photocarcinogenesis and photoaging. In this review,
      two examples are given to illustrate this development: (1) the use of topically
      applied DNA repair enzymes to prevent UVB-radiation-induced damage and (2) the
      development of a novel assay that is based on the detection of UVA-radiation
      induced mutations in mitochondrial DNA and can be used to study the efficacy of
      protective measures against photoaging of human skin.

PMID- 11598441
TI  - Pemphigus--paradigm of autoantibody-mediated autoimmunity.
AB  - Pemphigus encompasses a group of life-threatening autoimmune blistering diseases
      due to a loss of adhesion between keratinocytes, called acantholysis, which is
      caused by autoantibodies (AAb) against intercellular adhesion structures of
      epidermal keratinocytes. In pemphigus vulgaris (PV), the blisters are located in
      the suprabasal layer whereas in pemphigus foliaceus (PF), a clinically less
      severe disease, the blisters occur within the upper layers of the epidermis. In
      PV and PF, the AAb target the extracellular portions of desmoglein 3 (Dsg3) and
      Dsg1, respectively. AAb production in PV and PF is polyclonal and most AAb are of
      the IgG4 subclass in acute onset or active disease while patients in remission
      have mainly AAb of the IgG1 subtype. Evidence for the pathogenicity of these
      circulating AAb is provided by the observations that (1) the activity of
      pemphigus correlates with AAb titers, (2) newborns of mothers with active
      pemphigus temporarily exhibit blisters due to the transplacentar transfer of
      maternal AAb and (3) pemphigus-like lesions are induced in neonatal mice by
      transfer of IgG from PV patients. Clinically, pemphigus is characterized by
      extensive cutaneous blisters and erosions of the mucous membranes (PV). Patients
      with untreated pemphigus are prone to infections, loss of body fluids and
      proteins and to weight loss due to painful oral and esophageal erosions. The
      major therapeutic strategy in pemphigus is chronic immunosuppressive therapy with
      glucocorticosteroids in combination with immunosuppressive adjuvants.

PMID- 11598442
TI  - The skin: target organ in immunotoxicology of small-molecular-weight compounds.
AB  - Immunotoxicology studies two different effects of xenobiotics: immunosuppression
      and dysregulation of immune responses leading to hypersensitivity or
      autoimmunity. The skin is a major target organ of immunotoxicity which is
      provoked by small-molecular-weight compounds. Methods may be helpful for
      immunotoxicological investigations and screenings for adverse effects of
      xenobiotics which are used for diagnosis or studies on the pathophysiology of
      skin disorders such as allergic contact dermatitis, cutaneous drug-allergic
      reactions or autoimmune diseases of the skin. Examples include well-designed
      patch tests, assays involving antigen-presenting cells such as dendritic cells,
      but also T lymphocytes, basophiles or keratinocytes.

PMID- 11598443
TI  - Intracavitary therapy of noninvasive transitional cell carcinomas of the upper
      urinary tract. A review of the literature.
AB  - Noninvasive (stages Ta, T1, Tis) transitional cell carcinomas of the upper
      urinary tract are suitable for a conservative therapeutic approach. Intracavitary
      therapy (alone or as adjuvant treatment) has recently been proposed and
      successfully used by some authors. Even though bacillus Calmette-Guerin is the
      most frequent agent employed, chemotherapeutic drugs, such as mitomycin C and
      thiotepa, have also been successfully used. The current information available in
      the literature is therefore reviewed. According to the data available,
      intracavitary therapy is a worthwhile conservative therapeutic option for
      noninvasive upper urinary tract urotheliomas with acceptable side effects. For
      this reason it may be included in the routine urological armamentarium.

PMID- 11598444
TI  - Incidental splenectomy during left radical nephrectomy: reasons and ways to avoid
      it.
AB  - INTRODUCTION: Left radical nephrectomy is the second most common cause of
      incidental splenectomy during transabdominal oncological surgery in the upper
      left quadrant of the abdomen. The potential sequelae of splenic ablation are
      often underestimated and generally no systematic planned efforts have been
      undertaken to avoid a splenic injury. MATERIAL AND METHODS: We evaluated the
      incidence of iatrogenic splenectomy in 333 cases of left radical nephrectomy for
      renal cancer performed at our institute between 1970 and 1999. Two slightly
      different surgical techniques were adopted and after 1995 particular attention
      was paid to the possible causes of intraoperative splenic injury and how to avoid
      it. In the first group of patients (1970-1994) an anterolateral xipho-umbilical
      subcostal approach was used, and in the second group (1995-1999) a cruciate
      "Mercedes-like" incision was always adopted. RESULTS: The incidence of iatrogenic
      splenectomy in the first group of patients was 13.2%, and only 2.6% in the second
      group. The mortality rate in the first group of patients was 6%; no mortality has
      been recorded in the second group. Postoperative infections averaged 12.1% in the
      first group and 11.6% in the second, without any difference between the two
      groups. However, if we consider the incidence of postoperative infections in
      splenectomy cases, the incidence reaches 24.2% in the first group versus no cases
      in the second. CONCLUSIONS: Incidental splenectomy is a potentially severe
      complication of transabdominal left radical nephrectomy and is often considered a
      price that has to be paid, particularly in cases of large tumoral masses. A more
      detailed knowledge of splenic anatomy, a critical consideration of the
      intraoperative factors that may lead to splenectomy, and the adoption of a
      surgical tactic borrowed from the techniques of liver transplant significantly
      lower the incidence of iatrogenic splenectomy.

PMID- 11598445
TI  - Role of percutaneous image-guided biopsy in the evaluation of renal masses.
AB  - OBJECTIVE: The objective of the present study was to evaluate the indications,
      accuracy, complications and impact of image-guided percutaneous biopsy of renal
      masses. MATERIALS AND METHODS: Between 1994 and 1999, percutaneous biopsies under
      ultrasonography or computerized tomography guidance were performed in 33 patients
      with renal mass (22 men and 11 women, mean age 57.5 years, range 21-88). We
      retrospectively analyzed the relationship between clinical and histopathological
      findings, and discuss the appropriateness of the indications for image-guided
      percutaneous biopsy in the diagnosis of renal masses. RESULTS: The indications
      used in our institution were as follows: (1) clinical and radiological findings
      to suggest a diagnosis other than primary renal cell carcinoma (RCC) (n = 15);
      (2) suspicious lesions of RCC in multiple cystic renal masses (n = 7); (3)
      differentiation of transitional cell carcinoma of the renal pelvis from RCC (n =
      7); (4) differentiation of angiomyolipoma from RCC (n = 4). Sufficient amounts of
      tissues were obtained from all patients for pathological diagnosis. Among 33
      patients, 21 (63.6%) were diagnosed positive for malignancy, and 15 underwent
      surgical intervention. The histopathological findings between percutaneous biopsy
      and surgically resected tissue were identical in 13 cases (86.7%). No patient
      developed major complications requiring surgical treatment. CONCLUSION: If
      performed under appropriate selection of patients, percutaneous image-guided
      biopsy is a safe, reliable and accurate method of managing suspicious and/or
      indeterminate renal mass, and may contribute to the selection of appropriate
      clinical management by avoiding unnecessary procedures.

PMID- 11598446
TI  - Imperative indications for conservative surgery for renal cell carcinoma: 20
      years' experience.
AB  - INTRODUCTION: Radical nephrectomy is the treatment of first choice for unilateral
      renal cell carcinoma (RCC) with a healthy contralateral kidney; however, the
      current standard for dealing with RCC in patients with a solitary kidney,
      bilateral tumor and renal or systemic disease inducing a progressive impairment
      of renal function is nephron-sparing surgery. MATERIALS AND METHODS: Between
      January 1974 and July 1996, 62 patients (39 men and 23 women, 33-77 years old,
      mean age 60.6 years) with RCC underwent nephron-sparing surgery. The patients
      were divided in to two groups according to treatment indication: 46 patients with
      bilateral tumor (n = 21) or solitary kidney (n = 25) and 16 patients with renal
      or systemic disease that could damage the contralateral kidney. Survival curves
      were calculated according to the Kaplan-Meyer method. RESULTS: In the first group
      3 patients died postoperatively, and 3 were lost to follow-up; 12 patients
      (27.9%) had malignant recurrence and 5 (11.6%) died of local recurrence or
      systemic diffusion. The probability of local or systemic tumor recurrence was
      9.9% at 2 years, 20.2% at 5 years and 24.7% at 10 years; the probability of
      survival was 100% at 2 years, 91.9% at 5 years and 81.9% at 10 years. In the
      second group 3 patients died of unrelated causes and 1 was lost to follow-up; 4
      patients (25%) had a malignant recurrence and 2 (12.5%) died of systemic
      diffusion of RCC. The probability of tumor recurrence was 13.0% at 2 years, 19.7%
      at 5 years and 26.4% at 10 years, the probability of survival was 100% at 2
      years, 93.3% at 5 years and 86.1% at 10 years. CONCLUSIONS: In our experience
      nephron-sparing surgery seems justified in patients with a solitary kidney,
      bilateral tumor or a disease that potentially damages renal function. Tumor
      diameter and stage, incidental or symptomatic tumor presentation and specific
      indication for conservative surgery determine the prognosis.

PMID- 11598448
TI  - Radical prostatectomy in patients with previous groin hernia repair using
      synthetic nonabsorbable mesh.
AB  - OBJECTIVE: Identification of patients in whom the perineal route is the optimal
      approach to perform radical prostatectomy. MATERIAL AND METHODS: During 1992
      1999, 376 patients with prostate cancer underwent radical perineal prostatectomy.
      Four patients were identified in whom the perineal approach was indicated because
      of previous bilateral groin hernia repair using synthetic meshes. In addition, 1
      patient underwent perineal prostatectomy elsewhere for similar reasons. RESULTS:
      The perineal approach offered an uneventful surgical solution for an adequate and
      straightforward radical perineal prostatectomy without complications and without
      biochemical recurrence during the follow-up. CONCLUSION: Radical perineal
      prostatectomy is suggested to be the optimal approach in patients with previous
      bilateral groin hernia repair using synthetic, nonabsorbable meshes.

PMID- 11598447
TI  - Oat-cell carcinoma of the prostate. Diagnosis, prognosis and therapeutic
      implications.
AB  - BACKGROUND: Any carcinoma of prostatic origin which is not an acinary
      adenocarcinoma of the prostate is considered to be an atypical carcinoma. One
      member of this group of atypical prostatic tumors is the oat-cell carcinoma, or
      small cell carcinoma (SCC) of the prostate. This variety of carcinoma constitutes
      the histologic basis of <1% of all prostatic neoplasms. METHODS: Between 1992 and
      1997, four patients were diagnosed with SCC of the prostate at our hospital. In 3
      of the 4 cases, the histopathological diagnosis was pure SCC, and in the 4th case
      there was a component of prostatic adenocarcinoma associated with the SCC. At the
      time of diagnosis, extracapsular extension of the tumor was present in all 4
      cases, with T3 or higher stages in all of them (T(3A)N(0)M(1), T(3A)N(0)M(0),
      T(3B)N(0)M(1), and T(4)N(0)M(0)). Because of the presence of extracapsular
      extension, radiotherapy and radical surgery were ruled out for all 4 patients.
      They were all offered systemic chemotherapy with cyclophosphamide (1 g/m(2)),
      doxorubicin (50 mg/m(2)) and vincristine (1.2 mg/m(2)). This therapeutic protocol
      was carried out in only 2 cases. RESULTS: Survival was <1 year in the 3 patients
      with pure SCC, and the patient with a mixed tumor is alive with detectable
      disease 9 months after diagnosis. CONCLUSIONS: This poor vital prognosis in SCC
      stresses the need for early diagnosis a timely and appropriate therapeutic
      intervention in this condition.

PMID- 11598449
TI  - Liposome-mediated gene therapy using HSV-TK/ganciclovir under the control of
      human PSA promoter in prostate cancer cells.
AB  - To more accurately determine the tissue-specific expression of the target gene in
      prostate cancer cells, we introduced the enhancer element (-4,777 to -3,934;
      PSAR) and the promoter region (PSAP) of the prostate-specific antigen (PSA) gene.
      Furthermore, to elucidate the advantages of using liposomes as a gene carrier, we
      screened more than 20 liposome preparations in this study. The 5' upstream region
      of PSA gene (PSARPSAP) was conjugated to either the chloramphenicol
      acetyltransferase (CAT) gene or herpes simplex virus thymidine kinase (TK) gene,
      and the transfection of these plasmids was carried out using cationic liposomes,
      DMRIE-C (Gibco) or LipoTAXI (Stratagene). The expression of CAT activity was
      clearly observed when PSARPSAP-CAT plasmid was transfected into PSA-positive
      LNCaP cells, whereas no CAT activity was detected in PSA-negative DU145 cells or
      bladder carcinoma T24 cells. The CAT activity increased after the addition of
      testosterone. We then evaluated the therapeutic effect of the PSARPSAP-TK plasmid
      in vitro. When PSARPSAP-TK plasmid was transfected and ganciclovir was added to
      the medium, the growth of LNCaP cells was inhibited, while no growth inhibition
      was observed in DU145 cells. Furthermore, this inhibitory effect was observable
      even when the cells were cultured in a medium supplemented with dialyzed fetal
      bovine serum. These results suggest that the liposome-mediated transfection of
      PSARPSAP-TK appears to be a potentially effective approach for selecting the
      optimal treatment for tumor cells producing PSA even with the low androgen levels
      seen in patients treated by anti-androgen therapy.

PMID- 11598450
TI  - Superficial bladder tumors in patients under 40 years of age: clinical,
      prognostic and cytogenetic aspects.
AB  - Bladder carcinoma with transitional cells is the most frequent neoplasia in the
      urinary system, but it is quite rare in patients under 40 years of age (0.4-2%).
      An analysis of 21 patients under 40 and a review of other reports show that
      tumors in patients under 20 years old have little tendency to recur and to
      progress, while tumors in patients aged between 21 and 40 have a behavior pattern
      similar to older age groups regarding recurrence and disease progression.
      Preliminary results of a study using fluorescent in situ hybridization with
      probes for the centromere of chromosomes 7 and 17 showed a high incidence of
      aneusomy with regard to these chromosomes and a genetic difference between
      superficial tumors in the young and in adults. Using probes from chromosomes
      already described in bladder carcinogenesis, we obtained higher sensitivity and
      specificity in detecting aneuploid events.

PMID- 11598451
TI  - Endoscopic treatment of vesico-ureteral reflux: twelve years' experience.
AB  - INTRODUCTION: Over the past 12 years, endoscopic treatment of vesico-ureteral
      reflux (VUR) has gained in popularity and has proved successful in a high
      percentage of cases. With improvements in injectable materials and more
      experience with the technique, the indications for endoscopic treatment have
      broadened. In the present paper we report our experience on 679 patients and 953
      refluxing ureters, treated over the past 12 years. MATERIALS AND METHODS: Reflux
      ranged from grade II to grade IV. In the first 14 cases Teflon was injected.
      After 1989, bovine dermal collagen was used in 442 children and, more recently,
      the Deflux system, a nonallergenic, biodegradable dextranomer in sodium
      hyaluronan in 223 children. All patients were clinically investigated for voiding
      dysfunctions and all completed a 1-year follow-up. RESULTS: After 1 or 2
      injections the 1-year cystogram showed no VUR in 686 ureters (72%). In grade II,
      III and IV success rates were, respectively, 83, 69 and 41%. Complications were
      minimal (1%). CONCLUSIONS: Our results confirm endoscopic treatment of VUR is a
      valid alternative to long-term antibiotic prophylaxis and to open surgery in
      selected patients. The treatment often failed because of injected material
      displacement possibly due to voiding dysfunction. The short hospital stay,
      absence of significant postoperative complications, safety of the available
      injectable materials and high success rate suggest that endoscopic treatment
      should be offered to all children with grade II and III VUR, whereas it is
      questionable in patients with grade IV VUR. In patients with voiding dysfunction,
      appropriate therapy and voiding rehabilitation should precede treatment of VUR.

PMID- 11598452
TI  - Cadaver fascia lata sling in the treatment of intrinsic sphincter weakness.
AB  - Eight older women with stress incontinence caused by intrinsic urethral weakness
      underwent sling surgery with allogenic fascia lata. The tolerance of the material
      was excellent. In 1 case a secondary release of the fixation on the pecten was
      necessary because of too much tension; in the other cases the evolution was
      uneventful and resulted in perfect continence lasting for at least 2 years of
      follow-up.

PMID- 11598453
TI  - Genetic aberrations of NAT2 and chromosome 8: their association with progression
      in transitional cell carcinoma of the urinary bladder.
AB  - INTRODUCTION/OBJECTIVE: N-acetyltransferase 2 (NAT2), mapped to 8p22, is a
      polymorphic enzyme which metabolizes aromatic amines. Loss of heterozygosity of
      8p22 is associated with an increased risk of bladder cancer. This study evaluated
      NAT2 and chromosome 8 in sequential tumours from bladder cancer patients to
      determine if NAT2 alterations increase the risk of progression. MATERIALS AND
      METHODS: Thirty-seven sequential carcinomas from 19 patients were assessed using
      fluorescence in situ hybridization. RESULTS: Five carcinomas showed loss of NAT2;
      4 of these were from pTa/pT1 tumours. Polysomy 8 was observed in 4 of 14 (29%)
      primary carcinomas (pTa/pT1), in 4 of 12 (33%) pTa/pT1 recurrences, and in 90%
      (9/10) of the detrusor muscle invasive tumours (pT2+). 6 of 8 (75%) locally
      invasive tumours with polysomy 8 were from patients who subsequently developed
      disease progression (pT2+). In total, 13.5% (5/37) of the carcinomas were
      abnormal for NAT2, and 46% (17/37) were abnormal for chromosome 8 copy number.
      Polysomy 8 was associated with high grade (p = 0.01) and stage (p = 0.03) and
      disease progression (p = 0.03). CONCLUSION: Whilst there does not appear to be an
      association between loss of NAT2 and risk of progression in transitional cell
      carcinoma, the high rate of polysomy of chromosome 8 implies that other genes on
      this chromosome significantly influence disease progression.

PMID- 11598454
TI  - Electromyography of male rat perineal musculature during copulatory behavior.
AB  - Electromyogram (EMG) recordings were made from the bulbospongiosus (BS) and
      ischiocavernosus (IC) muscles of the awake male rat in order to evaluate the
      roles played by these muscles in the implementation of penile intromission during
      a copulatory encounter. Male rats with bipolar wire electrodes implanted
      chronically in the BS and IC muscles were mated with sexually receptive females.
      Concurrent videotape recordings established a relationship between EMG and
      components of male rat copulatory behavior, i.e. mount, intromission and
      ejaculation. On EMGs recorded from the IC muscle, the initial low-amplitude phase
      at the initiation of each behavioral component was distinguished from the late
      high-amplitude phase whenever the male accomplished mounting or intromission. In
      the BS muscle, the late high-amplitude phase was observed only when the male
      accomplished intromission. Power spectrum analysis by fast Fourier transformation
      revealed that in the IC muscle the two phases differed at an overall range of 100
      1,000 Hz. In the BS muscle, however, the spectra of the two phases differed at a
      specific range of 400-600 Hz. Recruitment of additional motor units would
      culminate in such a characteristic rise in the power spectrum. The results
      suggest that somatosensory inputs contingent on the intromission cause such
      recruitment in the BS to regulate penile cups and other movements.

PMID- 11598455
TI  - Perineal ectopic testis: a rare cause of empty scrotum.
AB  - Perineal ectopic testis is a rare congenital anomaly and remains a urologic
      curiosity. We report the course of 2 recurrent cases after hormonal therapy and a
      third case associated with inguinal hernia. During the surgical exploration, the
      gubernaculum testis was found fixed to the perineum. The testes were placed in
      the scrotum. The evaluation of differential diagnosis of empty scrotum is
      recommended.

PMID- 11598456
TI  - Symptomatic unilateral renal angiomyolipoma in a child with tuberous sclerosis.
AB  - We report a case of unilateral renal angiomyolipoma in a 10-year-old boy with
      tuberous sclerosis. The case is worthy of attention because the symptoms occurred
      at an early age and because the lesion was unilateral, the latter confirmed at 11
      year follow-up. The presentation and treatment are discussed, and the pertinent
      literature is reviewed. The case demonstrates that it is of clinical importance
      to monitor renal involvement in children with tuberous sclerosis.

PMID- 11598457
TI  - A giant renal calculus treated without nephrectomy.
AB  - The case of a patient with a giant renal calculus weighing 770 g in a solitary
      functioning kidney is reported. A 57-year-old man presented with right lumbar
      pain and macroscopic hematuria, and a giant stone was diagnosed in his right
      kidney. Nine days after a percutaneous nephrostomy placement, the patient
      underwent selective right renal angiography and transcatheter superselective
      embolization due to a sudden gross hematuria observed from both the nephrostomy
      tube and urethra. Embolization was successful. Right anatrophic nephrolithotomy
      was performed after stabilization of the patient. There were no complications
      during the recovery period. The case reported here is significant not only
      because it is the 7th biggest and the heaviest stone in the literature but also
      because it is the first giant stone reported to be in a solitary functioning
      kidney and treated without nephrectomy.

PMID- 11598458
TI  - Paratesticular liposarcoma in a transplanted patient.
AB  - A case of paratesticular liposarcoma in a transplanted patient is presented.
      Liposarcomas of the urogenital system are very rare tumors and have never before
      been reported in an immunosuppressed transplanted patient. We present a case of
      considerable clinical interest, our therapeutic approach and the final outcome.

PMID- 11598459
TI  - Development of a homogeneous high throughput fluorescence polarization assay for
      G protein-coupled receptor binding.
AB  - Traditional methods that follow receptor ligand interactions are competitive
      assays in which the test compound displaces a radiolabeled molecule. These assays
      require either a time-consuming step for separation of free ligands from bound
      ligands or immobilization of receptors and the scintillant on a solid-phase
      support. In this report, we describe the development of a homogeneous binding
      assay for a G protein-coupled receptor in the fluorescence polarization format.
      This homogeneous fluorescence polarization binding assay format is superior to
      the traditional binding methods because no radioisotope, separation step, or
      solid-phase support is required. The elimination of the separation step enhances
      detection of low-affinity ligands and enables a real-time, continuous readout of
      the binding activity in a high throughput 384-well microplate format.

PMID- 11598460
TI  - The design and development of an integrated natural products screening database.
AB  - We designed and developed NEXUS--a new natural products screening database and
      related suite of software applications--to utilize the spectacular increases in
      assay capacity of the modern high throughput screening (HTS) environment. NEXUS
      not only supports seamless integration with separate HTS systems, but supports
      user-customized integration with external laboratory automation, particularly
      sample preparation systems. Designed and developed based on a detailed process
      model for natural products drug discovery, NEXUS comprises two integrated parts:
      (1) a single schema of Oracle tables and callable procedures and functions, and
      (2) software "front-ends" to the database developed using Microsoft Excel and
      Oracle Discovery/2000. Many of the back-end processing functions were written in
      Programming Language/Structured Query Language (PL/SQL) to provide an Application
      Programmer's Interface, which allows end users to create custom applications with
      little input from information technology professionals.

PMID- 11598462
TI  - Detection of oligonucleotide-ligand complexes by ESI-MS (DOLCE-MS) as a component
      of high throughput screening.
AB  - With the advent of combinatorial chemistry and high throughput screening, a major
      bottleneck in the pharmaceutical industry has changed from quickly finding active
      compounds to limiting them to a manageable number for proper follow-up. With
      hundreds to thousands of active compounds identified by a multitude of biological
      screens, there need to be rapid and unambiguous methods for eliminating false
      positive, toxic, or otherwise difficult compounds from further scrutiny. We have
      used electrospray ionization mass spectrometry as a rapid screening method to
      identify compounds from viral screens that yield a positive assay response by
      interaction with DNA rather than inhibiting the target enzyme. Both the sample
      preparation and data acquisition have been automated, allowing the screening of
      all hits from relevant biological screens (up to 1,000/week). The assay was
      validated using several known DNA intercalators and minor groove binders. These
      "standards" and many but not all of our "active compounds" were shown to form
      noncovalent complexes with a variety of different DNA:DNA and DNA:RNA duplexes.

PMID- 11598461
TI  - Isolation of peptide ligands that inhibit glutamate racemase activity from a
      random phage display library.
AB  - Several new antibacterial agents are currently being developed in response to the
      emergence of bacterial resistance to existing antibiotic substances. The new
      agents include compounds that interfere with bacterial membrane function. The
      peptidoglycan component of the bacterial cell wall is synthesized by glutamate
      racemase, and this enzyme is responsible for the biosynthesis of d-glutamate,
      which is an essential component of cell wall peptidoglycan. In this study, we
      screened a phage display library expressing random dodecapeptides on the surface
      of bacteriophage against an Escherichia coli glutamate racemase, and isolated
      specific peptide sequences that bind to the enzyme. Twenty-seven positive phage
      clones were analyzed, and seven different peptide sequences were obtained. Among
      them, the peptide sequence His-Pro-Trp-His-Lys-Lys-His-Pro-Asp-Arg-Lys-Thr was
      found most frequently, suggesting that this peptide might have the highest
      affinity to glutamate racemase. The positive phage clones and HPWHKKHPDRKT
      synthetic peptide were able to inhibit glutamate racemase activity in vitro,
      implying that our peptide inhibitors may be utilized for the molecular design of
      new potential antibacterial agents targeting cell wall synthesis.

PMID- 11598463
TI  - Development of a fluorescent ligand-binding assay using the AcroWell filter
      plate.
AB  - One of the most powerful tools for receptor research and drug discovery is the
      use of receptor-ligand affinity screening of combinatorial libraries. Early work
      involved the use of radioactive ligands to identify a binding event; however,
      there are numerous limitations involved in the use of radioactivity for high
      throughput screening. These limitations have led to the creation of highly
      sensitive, nonradioactive alternatives to investigate receptor-ligand
      interactions. Pall Gelman Laboratory has introduced the AcroWell, a patented low
      fluorescent-background membrane and sealing process together with a filter plate
      design that is compatible with robotic systems. Taken together, these allow the
      AcroWell 96-well filter plate to detect trace quantities of lanthanide-labeled
      ligands for cell-, bead-, or membrane-based assays using time-resolved
      fluorescence. Using europium-labeled galanin, we have demonstrated that
      saturation binding experiments can be performed with low-background fluorescence
      and signal-to-noise ratios that rival traditional radioisotopic techniques while
      maintaining biological integrity of the receptor-ligand interaction. In addition,
      the ability to discriminate between active and inactive compounds in a mock
      galanin screen is demonstrated with low well-to-well variability, allowing
      reliable determination of positive hits even for low-affinity interactions.

PMID- 11598464
TI  - Development of a homogeneous time-resolved fluorescence assay for high throughput
      screening to identify Lck inhibitors: comparison with scintillation proximity
      assay and streptavidin-coated plate assay.
AB  - This study details the development of a homogeneous time-resolved fluorescence
      (HTRF) high throughput screening assay to identify inhibitors of Lck. HTRF was
      compared with scintillation proximity and streptavidin-coated plate assays.
      Because of the differences in the sensitivity of detection of phosphotyrosine
      among the three assays, different amounts of enzyme were used. However, the
      concentrations of the other assay components were standardized. When using
      similar assay conditions, the calculated IC(50) values of inhibitory compounds
      were independent of assay format. Furthermore, filtration experiments revealed
      that phosphorylation of a biotinyl poly-Glu,Ala, Tyr peptide substrate was less
      than autophosphorylation of the Lck enzyme; this was due to the low K(m) value
      for biotinyl poly-Glu,Ala,Tyr. In the HTRF assay, small amounts of enzyme and
      high concentrations of ATP could be used, thereby minimizing the effects of
      autophosphorylation. Higher ATP concentration would also minimize the effect of
      ATP competitors. Using this technology, it may be possible to find novel kinase
      inhibitors that do not act at the ATP binding site of protein tyrosine kinases.

PMID- 11598465
TI  - Practice parameters for the identification and testing of patients at risk for
      dominantly inherited colorectal cancer.

PMID- 11598466
TI  - Practice parameters for the identification and testing of patients at risk for
      dominantly inherited colorectal cancer--supporting documentation.

PMID- 11598468
TI  - Randomized, controlled trials in surgery: perceived barriers and attitudes of
      Australian colorectal surgeons.
AB  - PURPOSE: Although the randomized, controlled trial has gained preeminence as the
      criterion standard for evaluating pharmaceutical treatments, randomized
      controlled trials in surgery have been perceived as difficult to surmount.
      Furthermore, attitudes of surgeons toward randomized, controlled trials are not
      well understood. We determined the views of Australian surgeons about feasibility
      of and barriers to surgical randomized trials. METHODS: All members of the
      Section of Colon and Rectal Surgery of the Royal Australasian College of Surgeons
      (n = 147) and all Australian colorectal subspecialist surgeons (n = 72) were
      mailed a questionnaire that included questions about surgical randomized,
      controlled trials. RESULTS: A total of 195 surgeons responded (89 percent). Two
      thirds (66.7 percent; 95 percent confidence interval 59.5-73.1) of respondents
      agreed that "Randomized controlled trials should be the study design of choice"
      to evaluate new surgical procedures. Only 19 percent (95 percent confidence
      interval 13.9-25.3) endorsed the statement that "too much emphasis is placed on
      results of randomized controlled trials." Barriers to conducting surgical
      randomized, controlled trials identified by the majority included insufficient
      funding (74.4 percent; 95 percent confidence interval 67.5-80.2), a lack of
      support from the wider surgical community (55.9 percent; 95 percent confidence
      interval 48.6-62.9), and difficulties in convincing patients to accept random
      allocation to treatment (62.6 percent; 95 percent confidence interval 55.3-69.3).
      CONCLUSION: These results reveal positive attitudes among Australian surgeons
      toward randomized, controlled trials, although concerns about the feasibility of
      randomized, controlled trials have been reinforced.

PMID- 11598469
TI  - Outcome of sphincteroplasty combined with surgery for urinary incontinence and
      pelvic organ prolapse.
AB  - PURPOSE: This is the first reported prospective study comparing outcome and cost
      in patients undergoing sphincteroplasty for anal incontinence vs.
      sphincteroplasty performed in combination with one or more procedures for urinary
      incontinence and/or pelvic organ prolapse. METHODS: We analyzed 44 patients with
      fecal incontinence who underwent anal sphincter repair alone (20 patients) or in
      combination with procedures for urinary incontinence or pelvic organ prolapse (24
      patients). Information regarding risk factors for fecal incontinence, the degree
      of incontinence, and the extent that incontinence limited social, physical, and
      sexual activity was prospectively obtained from questionnaires. Clinic chart
      reviews and follow-up telephone interviews provided additional data. A cohort of
      case-matched patients who underwent only urogynecologic procedures was compared
      retrospectively for operative time, hospital cost, length of stay, and
      postoperative complications. RESULTS: There were no major complications in any
      group. The functional outcomes, physical, social, and sexual activity were
      similar in all three groups. Twenty-two of 24 patients who underwent the combined
      procedures were glad that they had both procedures concomitantly. CONCLUSION:
      Combination pelvic floor surgery provides good outcomes and is cost effective.
      This approach should be offered to women with concurrent problems of fecal and
      urinary incontinence and/or pelvic organ prolapse.

PMID- 11598470
TI  - Complications of dynamic graciloplasty: incidence, management, and impact on
      outcome.
AB  - PURPOSE: Dynamic graciloplasty can improve continence in patients with severe
      refractory fecal incontinence, but associated morbidity is high. The purpose of
      this study was to identify complications associated with dynamic graciloplasty
      and to characterize their treatment and impact on patient outcome. METHODS: In
      121 patients enrolled in a prospective trial of 20 centers and eligible for
      safety analysis, all complications of dynamic graciloplasty were recorded at the
      time of their occurrence and followed up until resolution. Severe treatment
      related complications were defined as those requiring hospitalization or surgical
      intervention. RESULTS: In 93 patients, 211 complications occurred. Of these, 89
      (42 percent) in 61 patients were classified as severe treatment-related
      complications and resulted from the following: major infection, 19; minor
      infection, 10; thromboembolic events, 3; device performance and use, 13; pain,
      16; noninfectious gracilis problems, 8; noninfectious wound-healing problems, 3;
      other surgery-related complications, 3. In addition, severe treatment-related
      complications resulted from constipation in ten and stoma creation or closure in
      ten. The recovery rate (full or partial) was 87 percent overall, and for severe
      treatment-related complications, was 92 percent. Of the types of complications,
      only major infections had an adverse effect on outcome. CONCLUSION: Severe
      complications occur frequently after dynamic graciloplasty, but are usually
      treatable. They often require one or more reoperations and can lead to
      significant delays in completion of therapy. In most cases therapy can be
      salvaged.

PMID- 11598471
TI  - Cyclosporin for severe ulcerative colitis does not increase the rate of
      perioperative complications.
AB  - PURPOSE: Cyclosporin is used in severe ulcerative colitis that is refractory to
      intravenous steroids. Cyclosporin is a potent immunosuppressant and can cause
      side effects such as opportunistic infections. This study aimed to investigate
      the incidence of perioperative complications in patients treated with intravenous
      cyclosporin and steroids compared with patients treated with intravenous steroids
      alone. METHODS: We retrospectively reviewed the case notes of 44 patients with
      severe ulcerative colitis who underwent total abdominal colectomy and ileostomy.
      Twenty-five patients were treated with intravenous steroids and 19 patients were
      treated with intravenous cyclosporin and steroids. Details were recorded with
      respect to age, length of illness, extent of disease, Truelove and Witt's
      criteria, hemoglobin and albumin at surgery, surgical procedure, and
      perioperative morbidity. RESULTS: Twenty-four percent of patients treated with
      intravenous steroids alone and 15.8 percent of patients treated with intravenous
      cyclosporin and steroids had major surgical complications. Sixteen percent of
      patients treated with intravenous steroids alone and 5.2 percent of patients
      treated with intravenous cyclosporin and steroids had minor surgical
      complications. Eight percent of patients treated with intravenous steroids alone
      and 10.5 percent of patients treated with intravenous cyclosporin and steroids
      had major medical complications. There was no mortality in either group.
      CONCLUSIONS: There is no increased incidence of perioperative complications
      associated with the use of intravenous cyclosporin in addition to steroids in
      acute severe ulcerative colitis provided cyclosporin treatment is for a defined
      period and surgery is not delayed.

PMID- 11598472
TI  - Laparoscopic total colectomy for acute colitis: a case-control study.
AB  - INTRODUCTION: There are no previous comparative studies of total abdominal
      colectomy by laparoscopic methods in ulcerative colitis and Crohn's disease
      patients requiring urgent colectomy. This study aimed to determine the safety and
      efficacy of laparoscopic colectomy in these patients compared with those
      undergoing conventional urgent colectomy. METHODS: Patients undergoing
      laparoscopic total colectomy for acute colitis were identified in a prospective
      registry. All patients underwent a total colectomy with creation of an end
      ileostomy and buried mucous fistula. No patient had fulminant disease
      (tachycardia, fever, marked leukocytosis, peritonitis), but all were failing to
      respond to medical treatment. Patients undergoing conventional total colectomy
      were matched for age, gender, body mass index, diagnosis, disease severity, and
      operative period. Median values (range) are listed. RESULTS: From 1997 to 1999,
      there were 19 laparoscopic and 29 matched conventional patients. There were no
      inadvertent colotomies or conversions in the laparoscopic group. Although there
      was no difference in operative blood loss in the laparoscopic group (100 (range,
      50-700) ml) when compared with the conventional group (150 (range, 50-500) ml),
      the operative times were significantly longer in the laparoscopic group (210
      (range, 150-270) vs. 120 (range, 60-180) minutes, P < 0.001). Bowel function
      returned more quickly in the laparoscopic group (1 (range, 1-3) vs. 2 (range, 1
      4) days; P = 0.003) and the length of stay was shorter (4 (range, 3-13) vs. 6
      (range, 4-24) days; P = 0.04). Complications occurred in three (16 percent)
      laparoscopic patients (2 wound infection and 1 ileus) and in seven (24 percent)
      conventional patients (3 wound infection, 3 deep venous thrombosis, 1 upper
      gastrointestinal bleed). CONCLUSIONS: Laparoscopic total colectomy is feasible
      and safe in patients with acute nonfulminant colitis and may lead to a faster
      recovery than conventional resection.

PMID- 11598473
TI  - Flow cytometric and histologic evaluation in a large cohort of patients with
      ulcerative colitis: correlation with clinical characteristics and impact on
      surveillance.
AB  - PURPOSE: To examine the prevalence of DNA aneuploidy as a function of the extent
      of ulcerative colitis and to study the correlation of aneuploidy with clinical
      characteristics. Furthermore, the occurrence of aneuploidy and dysplasia during
      colonoscopic surveillance was studied in a subset of these patients. METHODS: By
      analyzing 5404 biopsy samples of 368 patients with ulcerative colitis, we have
      evaluated the importance of DNA ploidy measured by flow cytometry. We have also
      investigated the influence of extent (219 patients with extensive or total
      colitis vs. 149 patients with localized colitis) and duration of colitis on the
      development of dysplasia (patients with biopsy specimens that showed inflammation
      alone were compared with those with biopsy specimens that were equivocal or
      positive for dysplasia) and aneuploidy. Included was a subgroup of patients with
      ulcerative colitis and primary sclerosing cholangitis (n = 16). RESULTS:
      Aneuploidy was found in 8.7 percent (32/368) of all patients. The prevalence of
      aneuploidy increased by the extent of ulcerative colitis (2 percent localized,
      6.8 percent extensive colitis, 14.9 percent total colitis). The frequency of
      aneuploidy was higher in patients with disease duration longer than 10 years (P =
      0.007). Patients with ulcerative colitis and primary sclerosing cholangitis were
      more likely to develop aneuploidy (9/16, 56.3 percent vs. 14/120, 11.7 percent; P
      < 0.001) and dysplasia (4/16, 25 percent vs. 10/120, 8.3 percent; P = 0.06) than
      patients without primary sclerosing cholangitis. CONCLUSION: Because DNA
      aneuploidy represents an early alteration during neoplastic transformation in
      ulcerative colitis, flow cytometry is a valuable tool in the surveillance of
      those patients. Primary sclerosing cholangitis represents an additional risk
      factor for the development of DNA aneuploidy and dysplasia.

PMID- 11598474
TI  - The value of specialization--is there an outcome difference in the management of
      fistulas complicating diverticulitis.
AB  - PURPOSE: The value of specialization has frequently been challenged by many
      health care institutions and providers. This review was conducted to determine
      whether there were any outcome differences in the management of fistulas
      complicating diverticulitis. METHODS: We conducted an historical cohort study
      using hospital charts of all cases of fistulas complicating diverticulitis that
      were operated on in four university-affiliated hospitals between 1975 and 1995.
      There were 122 patients, with 37 under the care of fully trained colorectal
      surgeons and 85 under the care of general surgeons. RESULTS: There were no
      significant differences in patient demographics, preoperative comorbidities, or
      the number of preoperative diagnostic investigations between the two groups. The
      colorectal surgeons performed more intraoperative ureteral stenting (Colorectal
      Surgery 55.5 percent vs. General Surgery 24.4 percent, P = 0.001). The general
      surgeons performed more initial diverting Hartmann's and colostomy procedures
      (Colorectal Surgery 5.4 percent vs. General Surgery 27 percent, P = 0.013). The
      patients in the General Surgery group had longer preoperative lengths of stay
      (median Colorectal Surgery 3 (range, 1-28) days vs. General Surgery 8 (range, 0
      29) days; P < 0.001), longer postoperative lengths of stay (median Colorectal
      Surgery 11 (range, 5-40) days vs. General Surgery 14 (range, 2-80) days; P =
      0.001), and longer total lengths of stay (median Colorectal Surgery 14 (range, 6
      62) days vs. General Surgery 24 (range, 6-100) days; P < 0.001). The patients in
      the General Surgery group experienced a higher rate of wound infections
      (Colorectal Surgery 5.4 percent vs. General Surgery 12.9 percent), and a larger
      proportion of them experienced complications (Colorectal Surgery 27 percent vs.
      General Surgery 41.2 percent). CONCLUSIONS: We conclude that specialization in
      colon and rectal surgery contributed to an improved outcome, with a lower rate of
      diverting procedures, a shorter hospital stay, and a lower rate of complications.

PMID- 11598475
TI  - Results of reoperations in colorectal anastomotic strictures.
AB  - PURPOSE: The incidence of colorectal anastomotic strictures varies from 3 to 30
      percent. Most of these anastomotic strictures are simple narrowings shorter than
      1 cm that can be successfully treated by dilation or endoscopic alternatives.
      However, up to 28 percent of patients will require surgical correction. This can
      be technically difficult, with the possibility of a permanent colostomy. This
      study reports the outcomes after operative treatment of severe strictures of
      colorectal anastomoses. METHODS: From August 1992 to October 1996, 27 patients
      were referred for surgical treatment of severe rectal anastomotic strictures. The
      reasons for the initial surgery were as follows: rectal cancer (13), diverticular
      disease (7), Hirschsprung's disease (2), rectal endometriosis (2), uterine
      carcinoma with rectal invasion (1), ruptured abdominal aortic aneurysm with
      rectosigmoid necrosis (1), and rectovaginal fistula (1). There were 15 (56
      percent) stapled anastomoses, and 21 (78 percent) patients had developed a
      postoperative leak. RESULTS: The median time between initial surgery and
      diagnosis of the stenosis was 7.2 (range, 1-24) months and between the last
      operation and referral was 15.1 (range, 1-44) months. Stenosis was located at a
      mean distance of 9.5 (range, 4-15) cm from the anal verge. Eleven patients (41
      percent) had been unsuccessfully dilated before referral. Surgical correction of
      the stenosis required 7 colorectal anastomoses for upper rectal anastomotic
      strictures and 20 coloanal anastomoses for middle and lower rectal strictures (19
      Soave's procedures and 1 colon J-pouch-anal anastomosis). Intestinal continuity
      was restored in all cases. After a mean follow-up of 28.7 +/- 14 months, no
      recurrences were detected and functional results were satisfactory. CONCLUSIONS:
      Resection of the stenosis and construction of a new colorectal anastomosis can be
      performed successfully for upper rectal anastomotic stricture. For a stenosis
      located in the middle and lower rectum, Soave's procedure offers a good
      alternative, with satisfactory long-term functional results. Whichever technique
      is used, a permanent colostomy should rarely be required.

PMID- 11598476
TI  - Early reoperation for perirectal abscess: a preventable complication.
AB  - PURPOSE: The aim of this study was to analyze failures in the operative
      management of perirectal abscesses resulting in early reoperation. METHODS: This
      was a retrospective case study of 500 consecutive patients who underwent 627
      drainage procedures for a perirectal abscess. RESULTS: Forty-eight patients (7.6
      percent of all drainage procedures) required reoperation within ten days of the
      original procedure. The main factors leading to reoperation were incomplete
      drainage (23 patients), missed loculations within a drained abscess (15
      patients), missed abscesses (4 patients), and postoperative bleeding (3
      patients). Incomplete drainage was more common with simple perirectal abscesses,
      whereas most overlooked collections were located posteriorly. Horseshoe abscesses
      were associated with a particularly high rate (50 percent) of operative failures.
      Neither preexisting perianal pathology nor systemic immunosuppressive disease
      contributed to early failures. CONCLUSION: Surgical errors are the leading cause
      of early failures in the surgical treatment of perianal abscesses. These errors
      occur in a limited number of typical patterns and can therefore be identified and
      taught with an aim to decrease their occurrence.

PMID- 11598477
TI  - Anocutaneous advancement flap repair of transsphincteric fistulas.
AB  - PURPOSE: The purpose of this study was to evaluate the healing rate of
      transsphincteric perianal fistulas after anocutaneous advancement flap repair and
      to examine the impact of this procedure on fecal continence. METHODS: Between
      January 1997 and June 1999, 26 consecutive patients with a transsphincteric
      perianal fistula passing through the middle or upper third of the external anal
      sphincter underwent anocutaneous advancement flap repair. There were six female
      patients, and the median age was 39 (range, 27-54) years. Twenty patients (77
      percent) had previously undergone one or more prior attempts at repair. With the
      patient in the prone-jackknife position, the internal opening of the fistula was
      exposed using a Lone Star Retractor System, and the crypt-bearing tissue around
      the internal opening as well as the overlying anoderm was excised. An (inverted)
      U-shaped flap, including perianal skin and fat, was created. The base of the flap
      was approximately twice the width of its apex. The flap was advanced and sutured
      to the mucosa and underlying internal anal sphincter proximal to the closed
      internal opening. The median follow-up time was 25 months. Fecal continence was
      evaluated in 23 patients by means of a questionnaire. RESULTS: Anocutaneous
      advancement flap repair was successful in 12 patients (46 percent). Success was
      inversely correlated with the number of prior attempts. In patients who had
      undergone no or only one previous attempt at repair (n = 9), the healing rate was
      78 percent. In patients with two or more previous repairs (n = 17) the healing
      rate was only 29 percent. In seven patients (30 percent) continence deteriorated
      after anocutaneous advancement flap repair. Eleven patients (48 percent) had a
      completely normal continence preoperatively. Two of these patients (18 percent)
      encountered soiling and incontinence for gas after the procedure, whereas two
      subjects (18 percent) complained of accidental bowel movements. Twelve patients
      (52 percent) presented with continence disturbances at the time of admission to
      our hospital. In this group, deterioration was observed in two patients (17
      percent). CONCLUSION: The results of anocutaneous advancement flap repair in
      patients with no or only one previous attempt at repair are moderate. In patients
      who have undergone two or more previous attempts at repair the outcome is poor.
      Based on the relatively low healing rate and deterioration of continence, this
      procedure seems less suitable for high transsphincteric fistulas than transanal
      mucosal advancement flap repair.

PMID- 11598478
TI  - Applicability of a mobile accelerator for intraoperative radiation therapy to
      colorectal cancer.
AB  - PURPOSE: Intraoperative radiation therapy is reportedly effective for local
      control and pain relief in colorectal cancer. However, this treatment requires a
      large number of medical personnel, which hinders expanded use of this method. A
      mobile electron linear accelerator for intraoperative radiation therapy has been
      developed and is now commercially available. This report analyzes the
      applicability of this accelerator to colorectal cancer. The applicability of the
      mobile accelerator is analyzed based on its specifications by simulating the
      intraoperative radiation therapy delivered to these patients with a conventional
      intraoperative radiation therapy unit. METHODS: From 1987 to 1999, 49 colorectal
      cancer patients underwent 54 surgical resections and received intraoperative
      radiation therapy to 75 sites. RESULTS: The mean intraoperative radiation therapy
      dose for colorectal cancer with the conventional unit was 22 (range, 10-30) Gy.
      The mean electron energy level was 10 (range, 3-30) MEV. Applicator size ranged
      from 4 to 10 cm in diameter. The mobile accelerator can achieve a dose rate of 10
      Gy/min and an applicator unit size range of 3 to 10 cm in diameter, facilitating
      intraoperative radiation therapy for colorectal cancer. The electron energy
      limitation (12 MEV at maximum) suggests that the indications for this machine are
      limited. In our experience, 30 percent of patients received intraoperative
      radiation therapy with electron energy levels exceeding 12 MEV. Of these cases,
      81 percent had macroscopic residual tumor and 69 percent had pain. CONCLUSION: An
      intraoperative radiation therapy mobile accelerator can cover 72 percent of the
      irradiation sites covered using our conventional unit. This accelerator is useful
      for intraoperative radiation therapy with curative intent for patients with no or
      slight residual tumor. Patients with gross residual tumor and pain may not be
      suitable.

PMID- 11598479
TI  - Efficacy of calcium dobesilate in treating acute attacks of hemorrhoidal disease.
AB  - PURPOSE: A randomized, double-blind, controlled study was conducted to
      investigate the efficacy of oral calcium dobesilate therapy in treating acute
      attacks of internal hemorrhoids. METHODS: Twenty-nine well-documented adult
      patients with first- or second-degree internal hemorrhoids were treated with
      calcium dobesilate for two weeks, while16 patients received only a high-fiber
      diet to serve as control. Both symptoms and anoscopic inflammation were scored on
      a scale from 0 to 2 before (T0) and two weeks after treatment (T2). RESULTS: A
      success rate of 86.21 percent with cessation of bleeding plus lack of severe
      anitis anoscopically at two weeks were achieved with calcium dobesilate. The
      pretreatment symptom score of 2 fell significantly to 0.45 +/- 0.13, and the
      pretreatment anitis score of 1.69 +/- 0.09 fell to 0.55 +/- 0.12 at T2 (P =
      0.0001 for both comparisons). The symptom and anoscopic inflammation scores
      obtained with calcium dobesilate treatment were also significantly better than
      those with diet only (P = 0.0017 and P = 0.0013, respectively). CONCLUSION:
      Together with recommendations about diet and bowel discipline, oral calcium
      dobesilate treatment provides an efficient, fast, and safe symptomatic relief
      from acute symptoms of hemorrhoidal disease. This symptomatic healing is
      associated with a significant improvement in the anoscopically observed
      inflammation.

PMID- 11598480
TI  - HIV-positive patients with anal carcinoma have poorer treatment tolerance and
      outcome than HIV-negative patients.
AB  - PURPOSE: Anal carcinoma is being found in HIV-positive patients with increasing
      frequency. Most patients are treated with combined chemotherapy and radiation. It
      was our impression that HIV-positive patients do not fare as well as HIV-negative
      patients in terms of both response to and tolerance of therapy. METHODS: To test
      this hypothesis, we reviewed our experience with anal carcinoma and compared HIV
      positive to HIV-negative patients by age, gender, sexual orientation, stage at
      diagnosis, treatment rendered, response to treatment, tolerance, and survival.
      From 1985 to 1998, 98 patients with anal neoplasms were treated. Seventy-three
      patients had invasive squamous-cell carcinoma (including cloacogenic carcinoma),
      and this cohort was analyzed. Thirteen patients were HIV positive and 60 were HIV
      negative. RESULTS: The HIV-positive and HIV-negative groups differed
      significantly by age (42 vs. 62 years, P < 0.001), male gender (92 vs. 42
      percent, P < 0.001), and homosexuality (46 vs. 15 percent, P < 0.05). There were
      no differences by stage at diagnosis or radiation dose received. Acute treatment
      major toxicity differed significantly (HIV positive 80 percent vs. HIV negative
      30 percent; P < 0.005). Only 62 percent of HIV-positive patients were rendered
      disease free after initial therapy vs. 85 percent of HIV-negative patients (P =
      0.11). Median time to cancer-related death was 1.4 vs. 5.3 years (P < 0.05). A
      survival model did not show age, gender, stage, or treatment to be independent
      predictors. CONCLUSION: We found that HIV-positive patients with anal carcinoma
      seem to be a different population from HIV-negative patients by age, gender, and
      sexual orientation. They have a poorer tolerance for combined therapy and a
      shorter time to cancer-related death. A strong trend to poorer initial response
      rate was also seen. These results suggest that the treatment of HIV-positive
      patients with anal carcinoma needs to be reassessed.

PMID- 11598481
TI  - Loss of heterozygosity and HIV infection in patients with anal squamous-cell
      carcinoma.
AB  - PURPOSE: This study was designed to determine whether loss of heterozygosity
      and/or microsatellite instability correlate with HIV infection and tumor
      recurrence after chemoradiation therapy in patients with squamous-cell carcinoma
      of the anus. BACKGROUND: The molecular mechanisms leading to the progression of
      HIV-related squamous-cell carcinoma of the anus are poorly understood. In
      particular, genetic alterations responsible for resistance to chemoradiation have
      important clinical and functional implications. METHODS: In a case-control study,
      we analyzed normal and tumor DNA samples of four patients with squamous-cell
      carcinoma of the anus who were successfully treated with chemoradiotherapy and
      four patients with radio-resistant squamous-cell carcinoma of the anus who
      required abdominoperineal resection for local recurrence. To determine the
      presence of microsatellite instability, we used the reference panel of five pairs
      of microsatellite primers recommended for colorectal cancer specimens. These
      include the microsatellite markers BAT25, BAT26, D5S346 (APC), D2S123 (hMSH2),
      and D17S250 (P53). In addition, we used microsatellite markers for loss of
      heterozygosity analyses that were tightly linked to tumor suppressor genes. These
      included D3S1611 (hMLH1), D17S513 (P53), D18S46 and 18qTA (DCC/SMAD4), D5S107
      (APC), and CA5 (hMSH2). RESULTS: There were two HIV-positive and two HIV-negative
      patients in each group. Three HIV-positive patients (one in the chemoradiotherapy
      group and two in the nonchemoradiotherapy group) demonstrated loss of
      heterozygosity. In the chemoradiotherapy group, one HIV-positive patient
      demonstrated loss of heterozygosity at the hMLH1 locus. In the
      nonchemoradiotherapy group, two HIV-positive patients exhibited a total of four
      instances of loss of heterozygosity. One tumor had loss of heterozygosity at
      hMSH2 and DCC/SMAD4; another tumor demonstrated loss of heterozygosity at hMSH2
      and APC. Microsatellite instability-low was found in two HIV-positive patients.
      No instances of loss of heterozygosity and microsatellite instability were
      detected in HIV-negative patients. CONCLUSION: Loss of heterozygosity and
      microsatellite instability, which reflect inactivation of tumor-suppressor genes
      and genomic instability, occur with increased frequency in HIV-associated
      squamous-cell carcinoma. These data demonstrate for the first time evidence of
      loss of heterozygosity at the APC and DCC/SMAD4 gene loci in anal carcinoma.
      Although the findings presented here need to be expanded in a larger study, the
      recurrent loss of heterozygosity at D2S123, which was demonstrated in HIV
      positive patients with radio-resistant squamous-cell carcinoma of the anus, is
      notable.

PMID- 11598482
TI  - Rectoanal motility in Crohn's disease patients.
AB  - PURPOSE: It has been documented that Crohn's disease affects anorectal function
      when anorectal manifestations of the disease are present. The aim of this study
      was to investigate whether the presence of histologic lesions in rectal biopsy
      affected anorectal motility in patients with Crohn's disease but no evidence of
      macroscopic anorectal involvement. METHODS: Forty-one patients with documented
      Crohn's disease were included in the study. Twenty-one of them had no endoscopic
      or histologic lesions in the rectum, and 20 patients had a positive histology for
      Crohn's disease on rectal biopsy, with or without macroscopic or endoscopic
      involvement of the anorectum. All patients underwent a standard anorectal
      manometry, with an eight-channel, water-perfused catheter. RESULTS: Patients with
      positive rectal biopsy but no evidence of endoscopic rectal involvement had lower
      anal resting and squeeze pressures (76 +/- 16 standard deviation vs. 86 +/- 19
      standard deviation P = 0.002; 152 +/- 56 standard deviation vs. 192 +/- 52
      standard deviation P < 0.001, respectively), and a lower sphincter and high
      pressure zone length (2.8 +/- 0.8 standard deviation vs. 3.2 +/- 0.8 standard
      deviation P = 0.006; 1.7 +/- 0.6 standard deviation vs. 2 +/- 0.6 standard
      deviation P = 0.005, respectively) compared with patients with negative rectal
      histology. Also, slow and ultra slow wave amplitude and ultra slow wave frequency
      were significantly lower (10 +/- 6 standard deviation vs. 13 +/- 7 standard
      deviation P = 0.04; 17 +/- 16 standard deviation vs. 34 +/- 24 SD P = 0.004; 0.9
      +/- 0.8 standard deviation vs. 1.3 +/- 0.6 standard deviation P = 0.05,
      respectively), rectal sensation more affected, and rectal compliance
      significantly reduced (7.4 +/- 1 standard deviation vs. 11.1 +/- 2.2 standard
      deviation P<0.001) in the former group of patients. Simultaneous presence of
      endoscopic and histologic lesions in the rectum was associated with further
      impairment of the anorectal function. CONCLUSION: Microscopic presence alone of
      Crohn's disease in the rectum appears to induce anorectal motility disorders. The
      synchronous presence of endoscopic rectal and macroscopic anal involvement is
      associated with further deterioration of anorectal function.

PMID- 11598483
TI  - Pilot study of subtotal colectomy with antiperistaltic cecoproctostomy for the
      treatment of chronic slow-transit constipation.
AB  - PURPOSE: Functional results of total colectomy with ileorectal anastomosis for
      the treatment of chronic constipation caused by colonic inertia are often
      considered unsatisfactory because of the frequency of postoperative diarrhea and
      the high rate of postoperative small-bowel obstruction. Patients affected by
      severe colonic inertia underwent a subtotal colectomy with a novel
      antiperistaltic cecorectal anastomosis. The aim of the study was to assess the
      functional results after preservation of the cecorectal junction. METHODS: Eight
      females affected by isolated colonic inertia and two females with both
      paradoxical puborectalis contraction and colonic inertia, of a median age of 40
      years, underwent subtotal colectomy with antiperistaltic cecorectal anastomosis.
      Before antiperistaltic cecorectal anastomosis all ten patients were laxative
      dependant, with a mean bowel frequency of ten days; eight of them (80 percent)
      had distention, seven (70 percent) bloating, and three (30 percent) abdominal
      pain. RESULTS: There was no mortality or major postoperative morbidity. One month
      after antiperistaltic cecorectal anastomosis, bowel frequency was a mean of 2.2
      (range, 1-4) per day, with a semiliquid stool consistency. After one year, bowel
      frequency was a mean of 1.3 (range, 0.5-3) per day, with a solid stool
      consistency; the same results were recorded at last follow-up. Although no
      patients used antidiarrheal medicine, laxatives continued to be used by both
      patients with paradoxical puborectalis contraction. All ten (100 percent) of the
      patients reported a good or improved quality of life. CONCLUSION: This
      preliminary experience seems to show that antiperistaltic cecorectal anastomosis
      is safe and effective for patients with colonic inertia. It results in prompt and
      prolonged relief from constipation for patients with isolated colonic inertia.

PMID- 11598484
TI  - Gastrointestinal actinomycosis: an unusual presentation with obstructive
      uropathy: report of a case and review of the literature.
AB  - A 55-year-old female patient is described who had recurrent retroperitoneal
      infections without an apparent focus. After a protracted period of illness the
      infection proved to be caused by actinomycosis. An unusual feature of the
      inflammatory process consisted of obstruction of the ureters, ultimately
      resulting in destruction of the left kidney. Hydronephrosis resulting from
      inflammatory fibrosis has not been reported in the literature before.

PMID- 11598485
TI  - Sweet's syndrome in association with Crohn's disease: report of a case and review
      of the literature.
AB  - A 41-year-old woman developed a skin rash as part of Sweet's syndrome concurrent
      with the first episode of Crohn's disease of the colon. Sweet's syndrome, acute
      febrile neutrophilic dermatosis, may be associated with inflammatory, infectious,
      or neoplastic diseases. Its association with Crohn's disease is very rare, and
      when reported it has been mainly associated with Crohn's colitis. This
      association has been described in various stages of the disease. Sweet's syndrome
      may be considered one of the extraintestinal manifestations of Crohn's disease.
      Early diagnosis of this dermatosis may be important because of the prompt
      response to treatment with corticosteroids. The value of metronidazole should be
      considered because this medication may enhance response to treatment.

PMID- 11598486
TI  - Endometriosis-associated invasive adenocarcinoma involving the rectum in a
      postmenopausal female: report of a case.
AB  - Sampson first reported a case of malignant transformation of endometriosis to
      adenocarcinoma in 1925. We present a case of such transformation occurring in a
      postmenopausal female 22 years after total abdominal hysterectomy and bilateral
      salpingo-oophorectomy. This case demonstrates histologic progression from
      endometriosis to complex hyperplasia with cytologic atypia, and ultimately to
      invasive endometrioid adenocarcinoma involving the rectum. Aggressive surgical
      extirpation of all visible colorectal endometriosis for patients with advanced
      disease is recommended.

PMID- 11598487
TI  - Rectosigmoid carcinoma at previous ureterosigmoidostomy site in a renal
      transplant recipient: report of a case.

PMID- 11598488
TI  - Bowel preparation for colorectal surgery.
AB  - PURPOSE: The aim of this study was to assess recent literature regarding bowel
      preparation for colonoscopy and surgery. METHODS: The study was conducted by an
      Index Medicus English-language search of articles relevant to both oral
      mechanical and parenteral and oral antibiotic preparation for elective colorectal
      surgery and mechanical bowel preparation for colonoscopy. The study period was
      from 1975 to 2000. In addition, studies of elective colorectal surgery without
      mechanical bowel preparation were also considered. RESULTS: Although several
      recent prospective, randomized trials have suggested that elective colorectal
      surgery can be safely performed without any mechanical bowel preparation,
      mechanical bowel preparation remains the standard of care, at least in North
      America at the present time. A recent survey of the members of The American
      Society of Colon and Rectal Surgeons revealed that the majority currently use
      sodium phosphate for bowel preparation and use a dual oral antibiotic regimen
      before elective colorectal surgery, combined with two doses of parenteral
      antibiotics. Although some of the use patterns are based on prospective,
      randomized study, others seem founded strictly on habit and theory. CONCLUSIONS:
      The current methods of bowel cleansing for both colonoscopy and surgery include
      sodium phosphate and polyethylene glycol; colorectal surgeons practicing in North
      America currently prefer sodium phosphate. Additional preparation for colorectal
      surgery includes perioperative parenteral antibiotics and, to a slightly lesser
      degree, preoperative oral antibiotic preparation. Although some recent
      prospective, randomized studies have suggested that omission of mechanical bowel
      preparation for elective colorectal surgery is not only feasible but potentially
      preferable, caution is recommended before routinely omitting these widely
      practiced measures, because data to support such routine omission are limited.

PMID- 11598490
TI  - An energy budget for signaling in the grey matter of the brain.
AB  - Anatomic and physiologic data are used to analyze the energy expenditure on
      different components of excitatory signaling in the grey matter of rodent brain.
      Action potentials and postsynaptic effects of glutamate are predicted to consume
      much of the energy (47% and 34%, respectively), with the resting potential
      consuming a smaller amount (13%), and glutamate recycling using only 3%. Energy
      usage depends strongly on action potential rate--an increase in activity of 1
      action potential/cortical neuron/s will raise oxygen consumption by 145 mL/100 g
      grey matter/h. The energy expended on signaling is a large fraction of the total
      energy used by the brain; this favors the use of energy efficient neural codes
      and wiring patterns. Our estimates of energy usage predict the use of distributed
      codes, with <or=15% of neurons simultaneously active, to reduce energy
      consumption and allow greater computing power from a fixed number of neurons.
      Functional magnetic resonance imaging signals are likely to be dominated by
      changes in energy usage associated with synaptic currents and action potential
      propagation.

PMID- 11598491
TI  - Measurement of cortical dopamine d1 receptor binding with 11C[SCH23390]: a test
      retest analysis.
AB  - [11C]SCH 23390 is a standard ligand for positron emission tomography (PET)
      studies on striatal dopamine D1 receptors. Its usefulness for cortical D1
      receptor quantification in human PET studies has been questioned but has not been
      addressed previously. The authors tested the reproducibility of [11C]SCH 23390
      binding potential (BP) in cortical areas in five healthy volunteers using three
      dimensional PET. Measurement of D1 receptor BP was reproducible in basal ganglia,
      as well as in all cortical areas studied (intraclass correlation coefficients
      between 0.81 and 0.92). The absolute variability in cortical areas was 9.21% +/-
      0.07%. The reproducibility of cortical D1 receptor BP measurement with [11C]SCH
      23390 is equal to that observed with a more recent D1-ligand, [11C]NNC 112.
      [11C]NNC 112 produces slightly higher specific-to-nonspecific binding ratios but
      has markedly slower kinetics resulting in a need for a longer scan time. These
      aspects should be considered when designing studies on the cortical D1-like
      receptors.

PMID- 11598492
TI  - Apomorphine-induced changes in synaptic dopamine levels: positron emission
      tomography evidence for presynaptic inhibition.
AB  - The authors developed a novel positron emission tomography method to estimate
      changes in the synaptic level of dopamine ([DA]) induced by direct dopamine
      agonists (for example, apomorphine) in patients with Parkinson disease. The
      method is based on the typical asymmetry of the nigrostriatal lesion that often
      occurs in Parkinson disease. Using the between-side difference (ipsilateral (I)
      and contralateral (C) putamen to the more affected body side) of the inverse of
      the putamen [11C]raclopride binding potential (BP), the authors obtained
      [equation: see text] at baseline (that is, before apomorphine administration) and
      [equation: see text] after apomorphine administration (assuming the concentration
      of apomorphine is equal in both putamina). The between-side difference in the
      estimated synaptic concentration of dopamine (diff[DA]) should remain constant
      unless apomorphine affects dopamine release differently between the two sides.
      The authors found that apomorphine given subcutaneously at doses of 0.03 and 0.06
      mg/kg induced significant changes in their estimate of diff[DA] (P < 0.05). Such
      changes were more pronounced when only patients with a stable response to
      levodopa were considered (P < 0.01). These findings provide in vivo evidence that
      direct dopamine agonists can inhibit the release of endogenous dopamine. The
      authors propose that this effect is mainly mediated by the activation of
      presynaptic D2/D3 dopamine receptors.

PMID- 11598493
TI  - Cerebral glucose transport implies individualized glial cell function.
AB  - Previous positron emission tomography (PET) measurements of cerebral glucose
      transport using [11C]-3-O-methylglucose (CMG) suggested an interindividual
      variation in the values of the rate constant of tracer outflow (k2) larger than
      that for the clearance rate of inflow (K1). These two parameters were examined in
      healthy cerebral cortex by dynamic PET in 4 men and 2 women (aged 24 to 73 years)
      without neurologic disease, and in 1 man (42 years) with a recent left
      hemispheric cerebral infarction under normoglycemia (average blood plasma d
      glucose concentration, 5.44 +/- 1.94 micromol/mL) and again under hyperglycemia
      (average, 10.24 +/- 1.44 micromol/mL). Time-radioactivity curves were obtained
      from healthy cortex (grey matter) and plasma and analyzed for the values of K1
      and k2 by two graphical approaches and two fitting procedures. Both K1 and k2
      significantly declined with increasing plasma glucose levels. A highly
      significant interindividual but not intraindividual variability for k2 was found
      at normoglycemia and hyperglycemia. The interindividual variability of K1,
      although borderline significant, was less than that of k2. Accordingly variable
      were the distribution volumes K1/k2. These data suggest individualized glial cell
      function and may be relevant to pathogenesis of neuropsychiatric disease.

PMID- 11598494
TI  - Magnetic resonance angiography in facial and other pain: neurovascular mechanisms
      of trigeminal sensation.
AB  - For much of the twentieth century migraine and cluster headache have been
      considered as vascular headaches whose pathophysiology was determined by changes
      in cranial vascular diameter. To examine nociceptive neural influences on the
      cranial circulation, the authors studied healthy volunteers' responses to
      injection of the pain-producing compound capsaicin in terms of the caliber of the
      internal carotid artery. The study was conducted using magnetic resonance
      angiographic techniques. Injection of capsaicin into the skin innervated by the
      ophthalmic (first) division of the trigeminal nerve elicited 40% +/- 27% (mean +/
      SD) increase in vascular cross-sectional area in the right (ipsilateral)
      internal carotid artery when compared with the mean baseline ( P < 0.001).
      Injection of capsaicin into the skin of the chin to stimulate the mandibular
      (third) division of the trigeminal nerve and into the leg led to a similar pain
      perception and failed to produce any significant change in vessel caliber. The
      data suggest that there is a highly functionally organized, somatotopically
      congruent trigeminal innervation of the cranial vessels, with a potent
      vasodilator effect of the ophthalmic division on the large intracranial vessels.
      The data are consistent with the notion that pain drives changes in vessel
      caliber in migraine and cluster headache, not vice versa. These conditions
      therefore should be regarded as primary neurovascular headaches not as vascular
      headaches.

PMID- 11598495
TI  - Phosphorylation of cyclic adenosine monophosphate response element binding
      protein in oligodendrocytes in the corpus callosum after focal cerebral ischemia
      in the rat.
AB  - Phosphorylation of cyclic adenosine monophosphate (AMP) response element binding
      protein (CREB) was examined immunohistochemically in the corpus callosum of the
      rat brain at various time points after 90-minute focal cerebral ischemia. Focal
      ischemia was induced by occlusion of the middle cerebral artery (MCA) using the
      intraluminal suture method. Sham animals showed that numerous oligodendrocytes
      (OLGs) constitutively express unphosphorylated CREB. Local cerebral blood flow
      (lCBF) measured by the 14C-iodoantipyrine method was reduced from 44.2 +/- 15.4
      (mL 100 g(-1) min(-1)) to 18.4 +/- 3.8 and from 53.9 +/- 14.4 to 4.8 +/- 4.5 in
      the medial and the lateral regions of the corpus callosum, respectively, during
      MCA occlusion (MCAO). After release of the MCAO, lCBF recovered to the control
      level in each region. The medial region of the corpus callosum showed a marked
      increase in phosphorylated CREB-positive OLGs at 3.5 hours of recirculation, and
      it remained increased until 2 weeks of recirculation as it gradually declined.
      The activation of CREB phosphorylation in the OLGs was accompanied by expression
      of antiapoptotic protein bcl-2, normal staining with cresyl violet, and negative
      TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      nick-end labeling) staining. Myelination detected by immunostaining with anti
      myelin basic protein (MBP) antibody and anti-myelin associated glycoprotein (MAG)
      antibody remained normal in the medial region of the corpus callosum. The lateral
      region of the corpus callosum showed a significant but only transient increase in
      phosphorylated CREB-positive OLGs at 3.5 hours of recirculation, which was
      followed by a rapid decrease during the subsequent recirculation period.
      Expression of bcl-2 was suppressed in this region, and demyelination became
      apparent. These findings suggest that signal transduction through CREB
      phosphorylation may be closely associated with survival of OLGs and maintenance
      of myelination in the corpus callosum after cerebral ischemia.

PMID- 11598496
TI  - Apoptotic and antiapoptotic mechanisms after traumatic brain injury.
AB  - Caspase and inhibitor of apoptosis (IAP) expression was examined in rats
      subjected to moderate traumatic brain injury (TBI) using a parasagittal fluid
      percussion brain insult (1.7 to 2.2 atm). Within 1 hour after injury, caspase-8
      and -9, two initiators of apoptosis, were predominantly expressed in superficial
      cortical areas adjacent to the impact site and in the thalamus. Caspase-3, an
      effector caspase, was evident at 6 hours throughout the traumatized cerebral
      cortex and hippocampus. Moreover, the authors observed that XIAP, cIAP-1, and
      cIAP-2, members of the IAP family, were constitutively expressed in the brain.
      Colocalization of XIAP-immunolabled cells with cell-specific markers indicated
      that XIAP is expressed within neurons and a subpopulation of oligodendrocytes.
      Immunoblots of brain extracts revealed that the processed forms of caspase-8, -9,
      and -3 are present as early as 1 hour after trauma. The appearance of activated
      caspases corresponded with the detection of cleavage of XIAP into fragments after
      injury and a concomitant increase in the levels of cIAP-1 and cIAP-2 in the
      traumatized hemispheres. The current data are consistent with the hypotheses that
      caspases in both the extrinsic and intrinsic apoptotic pathways are activated
      after moderate TBI and that IAPs may have a protective role within the brain with
      alterations in levels and cleavage of IAPs that contribute to cell death in this
      setting.

PMID- 11598497
TI  - Delayed, but marked, expression of apolipoprotein E is involved in tissue
      clearance after cerebral infarction.
AB  - Clearance of infarct tissue would be an important process for tissue repair after
      a stroke. Delayed clearance may hamper reconstitution of the blood-brain barrier
      and glial boundary formation. Recent growing evidence has indicated that
      apolipoprotein E (APOE), a major apoprotein, plays an important role in lipid
      transport and homeostasis in the brain. The tissue in the infarction contains
      abundant lipids must be removed for tissue clearance. In the current study, the
      authors investigated APOE expression after focal ischemia and the functional role
      of APOE in tissue clearance using APOE-knockout mice. Expression of APOE was
      delayed, but marked, in immunohistochemistry and immunoblotting 7 days after
      permanent focal ischemia. Macrophages were found to express APOE in the infarct
      center. Infarct size was similar after focal ischemia between wild-type and APOE
      knockout mice, although there was no APOE protein expression in knockout mice.
      However, clearance of infarct tissue 2 weeks after ischemia was significantly
      delayed in APOE-knockout mice compared with wild-type mice. The current study
      supports current thinking that APOE is a key molecule for tissue remodeling in
      the brain. Clearance of damaged tissue may be one of the important functions of
      APOE in the brain.

PMID- 11598498
TI  - Neuroprotective effects of the CRF1 antagonist R121920 after permanent focal
      ischemia in the rat.
AB  - The neuroprotective effects of a systemically active, highly selective,
      corticotropin-releasing factor-1 (CRF1) receptor antagonist, R121920 ((7
      (dipropylamino)-2,5-dimethyl-3- [2-(dimethylamino)-5-pyridyl] pyrazolo [1,5-a]
      pyrimidine), was assessed in two rat models of permanent focal cerebral ischemia,
      where the middle cerebral artery (MCA) was occluded either through the
      subtemporal approach or using the intraluminal suture technique. R121920 rapidly
      crossed the blood-brain barrier after intravenous (IV) bolus administration (10
      mg/kg), with peak brain concentrations at 5 minutes (2.26 +/- 0.40 microg/mL),
      which were approximately 2-fold greater than those in plasma (0.98 +/- 0.24
      microg/mL). Treatment with R121920 (10 mg/kg IV followed by 5 mg/kg
      subcutaneously at hourly intervals for 4 hours) significantly (P < 0.001) reduced
      total (by 40%) and cortical (by 37%) infarct volume at 24 hours after subtemporal
      MCA occlusion (MCAO). In the intraluminal suture MCAO model, IV administration of
      R121920 (10 mg/kg) at the time of ischemia onset (and at multiple times
      thereafter) reduced both hemispheric infarct volume (by 34%, P < 0.001) and brain
      swelling (by 50%, P < 0.001) when assessed at 24 hours. In this model of focal
      ischemia, significant reduction (P < 0.05) in both outcome measures was obtained
      when R121920 administration was delayed up to 1 hour after MCAO. These results
      further define the antiischemic properties of selective CRF 1 antagonists in two
      experimental models of permanent focal cerebral ischemia.

PMID- 11598499
TI  - Protective effect of heme oxygenase-1 gene transfer against oxyhemoglobin-induced
      endothelial dysfunction.
AB  - The current study was designed to determine the effect of recombinant heme
      oxygenase-1 (HO-1) gene expression on endothelial function in cerebral arteries.
      Isolated canine basilar arteries were exposed ex vivo (30 minutes at 37 degrees
      C) to an adenoviral vector (10(10) PFU/mL, total volume 300 microL) encoding
      either the HO-1 gene (AdCMVHO-1) or the beta-galactosidase (beta-Gal) reporter
      gene (AdCMVbeta-Gal). Twenty-four hours after transduction, arterial rings were
      suspended in organ chamber for isometric force recording. Endothelium-dependent
      relaxations were obtained in response to bradykinin (10(-10) to 10(-6) mol/L)
      during contraction to uridine-5'-triphosphate (UTP; 3 x 10(-6) to 3 x 10(-5)
      mol/L). Certain rings were incubated with oxyhemoglobin (OxyHb; 10(-5) mol/L)
      overnight (16 to 18 hours of 24 hours). Expression and localization of
      recombinant protein were shown by Western blot analysis and immunohistochemistry.
      Endothelium-dependent relaxation to bradykinin and endothelium-independent
      relaxation to forskolin (10(-9) to 10(-5) mol/L) and DEA-NONOate (10(-10) to 10(
      5) mol/L) were identical in beta-Gal- and HO-1-transduced arteries. Exposure to
      OxyHb caused impairment of endothelium-dependent relaxation to bradykinin (P <
      0.01). In contrast, OxyHb did not affect endothelium-dependent relaxation in
      arteries expressing recombinant HO-1 ( P > 0.05). This protective effect of HO-1
      was reversed by coincubation with tin protoporphyrin (SnPP9; 10(-5) mol/L), a
      selective inhibitor of HO-1 (P < 0.01). Basal levels of 3',5'-cyclic
      monophosphate (cGMP) in HO-1-transduced vessels were not significantly different
      from those in beta-Gal-transduced vessels. Pretreatment with OxyHb significantly
      reduced cGMP level in beta-Gal-transduced rings (P < 0.01), whereas it had no
      effect in HO-1-transduced rings. These results demonstrate that HO-1 gene
      transfer does not affect endothelial and smooth muscle function of normal
      arteries, and that expression of recombinant HO-1 in cerebral arteries protects
      vasomotor function against OxyHb-induced injury.

PMID- 11598500
TI  - Angiogenesis after stroke is correlated with increased numbers of macrophages:
      the clean-up hypothesis.
AB  - Brain cells manufacture and secrete angiogenic peptides after focal cerebral
      ischemia, but the purpose of this angiogenic response is unknown. Because the
      maximum possible regional cerebral blood flow is determined by the quantity of
      microvessels in each unit volume, it is possible that angiogenic peptides are
      secreted to generate new collateral channels; other possibilities include
      neuroprotection, recovery/regeneration, and removal of necrotic debris. If the
      brain attempts to create new collaterals, microvessel density should increase
      significantly after ischemia. Conversely, if angiogenic-signaling molecules serve
      some other purpose, microvessel densities may increase slightly or not at all. To
      clarify, the authors measured microvessel densities with quantitative
      morphometry. Left middle cerebral arteries of adult male Sprague-Dawley rats were
      occluded with intraluminal nylon suture for 4 hours followed by 7, 14, 19, or 30
      days of reperfusion. Controls received no surgery or suture occlusion. Changes in
      microvessel density and macrophage numbers were measured by light microscopic
      morphometry using semiautomated stereologic methods. Microvessel density
      increased only in the ischemic margin adjacent to areas of pannecrosis and was
      always associated with increased numbers of macrophages. Ischemic brain areas
      without macrophages displayed no vascularity changes compared with normal
      animals. These data suggest that ischemia-induced microvessels are formed to
      facilitate macrophage infiltration and removal of necrotic brain.

PMID- 11598502
TI  - Diseases desperate grown.

PMID- 11598501
TI  - GAT2/BGT-1 as a system responsible for the transport of gamma-aminobutyric acid
      at the mouse blood-brain barrier.
AB  - In this study, the gamma-aminobutyric acid (GABA) transporter at the blood-brain
      barrier (BBB) was identified by reverse transcription-polymerase chain reaction
      (RT-PCR), Western blot, and immunostaining analysis, and the transport mechanism
      was characterized using a conditionally immortalized mouse brain capillary
      endothelial cell line (TM-BBB) as an in vitro model of the BBB. gamma
      Aminobutyric acid transport was studied by the cellular uptake of [ 3 H]GABA.
      [3H]GABA uptake by TM-BBB cells was Na (+)-, Cl(-)-, and concentration-dependent.
      The corresponding Michaelis-Menten constant was 679 +/- 80 micromol/L and the
      maximal uptake rate was 4,790 +/- 494 pmol/(mg protein x 5 minutes). [3H]GABA
      uptake by TM-BBB cells was significantly inhibited by betaine, beta-alanine,
      nipecotic acid, taurine, and quinidine, whereas probenecid, L-proline, creatine,
      and glycine had no effect. This type of inhibition is consistent with the
      predominant involvement of the GAT2/BGT-1 transporter in TM-BBB cells. RT-PCR
      analysis showed that GAT2/BGT-1 mRNA was expressed in TM-BBB cells, whereas
      Western blot analysis showed that TM-BBB cells and mouse brain capillaries
      express GAT2/BGT-1 protein. Moreover, confocal immunofluorescent microscopy of
      dual-labeled mouse brain sections demonstrated the colocalization of GAT2/BGT-1
      and P-glycoprotein, a BBB-specific marker, on brain capillaries labeled with anti
      GAT2/BGT-1 antibody and anti-P-glycoprotein antibody, respectively. These results
      are evidence that GAT2/BGT-1 is expressed at the BBB and is involved in GABA
      transport across the BBB.

PMID- 11598503
TI  - Ultrastructural changes in paravertebral muscles associated with degenerative
      spondylolisthesis.
AB  - STUDY DESIGN: The paravertebral muscle of 30 patients with spondylolisthesis and
      30 control patients were investigated histologically. OBJECTIVE: To propose
      myopathologic paravertebral muscle changes in cases of degenerative lumbar
      spondylolisthesis. SUMMARY OF BACKGROUND DATA: The stability of the vertebral
      column is based on both active and passive systems. The passive system is
      composed of the vertebrae, the intervertebral discs, and the ligaments.
      Surrounding muscles and tendons constitute the active system. The autochthonous
      back muscles take over support functions if the passive system is ineffective. In
      some cases, muscles are overstrained for a long period, ultimately leading to
      muscular changes. This study was performed to determine the histopathologic
      correlates of this permanent strain. METHODS: Between July 1998 and July 1999,
      paravertebral muscle biopsies were performed for 30 patients with monosegmental
      degenerative spondylolisthesis undergoing posterior lumbar interbody fusion. The
      tissue samples were submitted to histologic analysis including immune and enzyme
      histochemistry and electron microscopy. In addition, the muscle fibers were
      submitted to morphometry. RESULTS: Severe pathologic alterations were found. The
      findings showed that 22 patients (73.3%) had ragged red fibers with evident
      ultrastructural mitochondrial anomalies. The cristae appeared irregular in 12
      patients (40%) Type 1 paracrystalline inclusions were detected in five samples
      (16.6%) and dense bodies in eight (26.6%). Fibers with ubiquitin-positive
      inclusions were detected by immunohistochemistry in 13 patients (43.3%). As shown
      by the electron microscope, these corresponded to granulofilamentous inclusions
      and polyglucosan bodies. The samples were submitted to genetical analysis because
      biochemical studies showed reduced activity of the respiratory chain enzymes.
      Normal mitochondrial deoxyribonucleic acids of unchanged length were detected.
      CONCLUSIONS: Apart from nonspecific myopathic changes such as those observed in
      rimmed vacuoles and rods, increased numbers of polyglucosan bodies were detected.
      This increase in polyglucosan bodies currently has not been described in patients
      with otherwise normal muscles.

PMID- 11598505
TI  - Effects of lidocaine on blood flow and endoneurial fluid pressure in a rat model
      of herniated nucleus pulposus.
AB  - STUDY DESIGN: An experimental study was conducted to evaluate the effects of
      lidocaine on nucleus pulposus-induced pathophysiologic changes. OBJECTIVES: To
      investigate the effects of lidocaine on blood flow in the hind paws and
      endoneurial fluid pressure in the dorsal root ganglia in a rat model of herniated
      nucleus pulposus, and to clarify the therapeutic mechanisms of nerve root
      infiltration. SUMMARY OF BACKGROUND DATA: It has been shown experimentally that
      application of nucleus pulposus to the nerve roots increases endoneurial fluid
      pressure and decreases blood flow in the dorsal root ganglia and the
      corresponding hind paw. These changes are thought to be an important pathogenic
      mechanism associated with sciatica caused by disc herniation. Nerve root
      infiltration is one of the nonoperative effective therapies for radiculopathy
      caused by disc herniation. However, the therapeutic mechanisms still are unknown.
      METHODS: For this study, 21 Sprague-Dawley rats were used. Autologous nucleus
      pulposus was applied to the nerve root with a piece of Spongel containing
      lidocaine (lido group) or physiologic saline solution (control group). In Series
      1 of this study (Blood Flow in the Hind Paw), blood flow in the corresponding
      hind paws was monitored continuously using a laser Doppler flowmeter before
      application of the test solutions, and every 5 minutes thereafter for an
      additional 3 hours in both the control (n = 5) and lido (n = 5) groups. In Series
      2 of this study (Endoneurial Fluid Pressure in the Dorsal Root Ganglion),
      endoneurial fluid pressure was recorded with a servo-null micropipette system
      using glass micropipettes before and 3 hours after application of the test
      solutions in both the control (n = 6) and lido (n = 5) groups. After
      measurements, dorsal root ganglia were assessed for histology. RESULTS: In Series
      1, blood flow in the corresponding hind paw in the control group showed
      significant reduction as compared with that of the Lido group, starting about 90
      minutes after application (P < 0.01-0.05). Hind paw blood flow in the lido group
      did not show any reduction during measurements. In Series 2, the value of
      endoneurial fluid pressure in the lido group 3 hours after application was
      significantly lower than in the control group (P < 0.01). Interstitial
      (endoneurial) edema in the dorsal root ganglion in the lido group appeared to be
      qualitatively less than in the control group. CONCLUSIONS: The data indicate that
      lidocaine reduces the pathophysiologic changes in the dorsal root ganglion and
      hind paws induced by nucleus pulposus. These effects of lidocaine may relate to
      the mechanisms underlying the therapeutic effects of nerve root infiltration.

PMID- 11598507
TI  - Effects of diclofenac and ketoprofen on nerve conduction velocity in experimental
      nerve root compression.
AB  - STUDY DESIGN: The effects of diclofenac and ketoprofen on nerve conduction
      velocity in experimental nerve root compression were evaluated in a setup using
      an established pig model. OBJECTIVE: To assess the effects of two potent
      nonsteroidal antiinflammatory drugs, diclofenac and ketoprofen, in experimental
      nerve root compression. SUMMARY OF BACKGROUND DATA: Compression of spinal nerve
      roots is recognized to be of major etiologic importance for several common spinal
      pain syndromes. Secondary inflammatory changes, induced by microvascular
      permeability changes and leakage of inflammatory mediators into the endoneural
      tissue, have been proposed as important for the induction of spinal nerve root
      injury by chronic compression. METHODS: This study involved 21 pigs. An ameroid
      constrictor was used to induce compression. Seven pigs were treated with daily
      intramuscular injections of diclofenac 3 mg/kg for 7 days. Seven other pigs were
      treated with daily intramuscular injections of ketoprofen 4 mg/kg. For a control,
      seven pigs did not receive any drug treatment. After 7 days, the pigs were
      reanesthetized, and the nerve conduction velocity in the compressed nerve root
      segments was determined. RESULTS: The nerve conduction velocity was significantly
      higher (P < 0.05, Student's t test) in the pigs treated with diclofenac (50 +/-
      16 m/second) than in the untreated pigs (32 +/- 15 m/second). The nerve
      conduction velocity also was significantly higher (P < 0.05) in the pigs treated
      with ketoprofen (59 +/- 16 m/second) than in the untreated pigs. There were no
      significant differences in nerve conduction velocity between pigs treated with
      ketoprofen and those treated with diclofenac. CONCLUSIONS: The findings indicate
      that intramuscular administration of diclofenac or ketoprofen, both potent
      antiinflammatory drugs, may reduce nerve root dysfunction induced by compression
      of spinal nerve roots in an experimental pig model.

PMID- 11598508
TI  - Acute biomechanical and histological effects of intradiscal electrothermal
      therapy on human lumbar discs.
AB  - STUDY DESIGN: Human cadaver lumbar spines were used to assess the acute effects
      of intradiscal electrothermal therapy in vitro. OBJECTIVE: To determine whether
      intradiscal electrothermal therapy produces acute changes in disc histology and
      motion segment stability. SUMMARY OF BACKGROUND DATA: Intradiscal electrothermal
      therapy has been introduced as an alternative for the treatment of discogenic low
      back pain. Several hypothesized mechanisms for the effect of intradiscal
      electrothermal therapy have been suggested including shrinkage of the nucleus or
      sealing of the anulus fibrosus by contraction of collagen fibers, and thermal
      ablation of sensitive nerve fibers in the outer anulus. METHODS: Intradiscal
      electrothermal therapy was performed with the Spinecath by Oratec on 19 fresh,
      frozen human lumbar cadaver specimens. In a separate study, eight specimens were
      tested biomechanically and instrumented to map the thermal distribution, whereas
      five specimens were tested only biomechanically, both before and after
      intradiscal electrothermal therapy. Six additional specimens were heated with
      intradiscal electrothermal therapy, and the resulting canal was backfilled with a
      silicone rubber compound to allow colocalization of the catheter and anular
      architecture. RESULTS: A consistent pattern of increased motion and decreased
      stiffness was observed. For the specimens in which only biomechanical
      measurements were taken, a 10% increase in the motion, on the average, at 5 Nm
      torque was observed after intradiscal electrothermal therapy. No apparent
      alteration of the anular architecture was observed around the catheter site in
      the intradiscal electrothermal therapy-treated discs. CONCLUSION: The data from
      this study suggest that the temperatures developed during intradiscal
      electrothermal therapy are insufficient to alter collagen architecture or stiffen
      the treated motion segment acutely.

PMID- 11598509
TI  - Slippage mechanism of pediatric spondylolysis: biomechanical study using immature
      calf spines.
AB  - STUDY DESIGN: This study analyzed the skeletal-age-dependent strength of the
      lumbar growth plate to resist anterior shearing forces using the MTS system in
      the immature calf spine with pars defects. OBJECTIVE: To clarify the
      pathomechanism of the skeletal-age-dependent incidence of slippage in pediatric
      patients with pars defects by comparing the strength of the lumbar growth plate
      among three skeletal age groups. SUMMARY OF BACKGROUND DATA: Isthmic
      spondylolisthesis occurs and progresses more frequently during the growth period,
      whereas it is rare afterward. However, little evidence has been demonstrated to
      elucidate the etiology. METHODS: For this study, 15 lumbar functional spine units
      were divided into three groups according to their skeletal ages. Five were from
      neonates (Group 1), five from calves approximately 2 months old (Group 2), and
      five from calves about 24 months old (Group 3). An anterior shearing force was
      applied to each specimen until failure, after bilateral pars defects were
      created. Failure load (newtons) and displacement at failure (millimeters) were
      calculated from the load-displacement curve. The site of failure was confirmed by
      plain radiograph. RESULTS: All 15 functional spine units failed at the growth
      plate. The failure load was 242.79 +/- 46.05 N in Group 1, 986.40 +/- 124.16 N in
      Group 2, and 2024.54 +/- 245.53 N in Group 3. Statistically significant
      differences were found among the three groups (P < 0.05). The displacement at
      failure was 7.52 +/- 1.84 mm in Group 1, 11.10 +/- 2.30 mm in Group 2, and 8.15
      +/- 2.66 mm in Group 3. There were no significant differences among the groups.
      CONCLUSIONS: The results indicate that the strength of the growth plate, the
      weakest link in this model, against anterior shearing forces depends on the
      skeletal maturity, and that the biomechanical weakness of the growth plate plays
      an important role in the slippage mechanism.

PMID- 11598511
TI  - Development of a system for in vitro neck muscle force replication in whole
      cervical spine experiments.
AB  - STUDY DESIGN: An in vitro biomechanical study. OBJECTIVES: To develop and
      evaluate a new in vitro whole cervical spine model that provides to the specimen,
      in vivo-like mechanical characteristics. SUMMARY OF BACKGROUND DATA: In vitro
      studies of kinematics, kinetics, and trauma using isolated spine specimens (head
      T1 vertebra) have usually applied upward force to the head, resulting in tensile
      spine forces, contrary to the physiological compressive forces present in vivo.
      Further, the in vitro load-displacement curves have never been compared with the
      corresponding in vivo data. METHODS: A novel muscle force replication (MFR)
      system is presented. It consists of a set of compressive forces applied to the
      various vertebrae and occiput of a whole cervical spine specimen. Two protocols,
      with and without MFR, were evaluated using standardized flexibility testing.
      Ranges of motion (ROM) and load-displacement curves were documented, and
      contrasted with similar in vivo data. RESULTS: Results for the MFR were found to
      be similar to the in vivo measurements, with respect to the intersegmental and
      whole neck motions as well as the load-displacement curves, thus validating the
      MFR approach. CONCLUSIONS: The new model advances the in vitro testing, which
      uses whole cervical spine specimens.

PMID- 11598512
TI  - Extensor musculature of the cervical spine after laminoplasty: morphologic
      evaluation by coronal view of the magnetic resonance image.
AB  - STUDY DESIGN: A radiographic study in 22 patients using magnetic resonance
      imaging was conducted. OBJECTIVE: To describe the relation between postoperative
      cervical alignment and morphologic evaluation of the cervical extensor
      musculature, especially semispinalis cervics in laminoplasty. SUMMARY OF
      BACKGROUND DATA: Cervical laminoplasty has been widely accepted as a treatment
      for cervical myelopathy. Posterior procedures, however, involve the extensor
      musculature of the cervical spine. METHODS: In this study, 22 patients who
      underwent laminoplasty for repair of the extensor musculature were reviewed
      prospectively. The semispinalis cervics was evaluated by coronal view of the
      magnetic resonance image 1 month, 12 months, and 24 months after surgery.
      Cervical alignment at last follow-up assessment was compared with preoperative
      alignment using the lateral view of cervical radiographs. RESULTS: In 18 patients
      (82%), morphologic repair of semispinalis cervics had been maintained (Group A),
      but in 4 patients (18%), but it had not been maintained at the last follow-up
      assessment (Group B). Cervical alignment in Group A had been maintained, but
      maximum loss of cervical lordosis occurred in Group B. Moreover, Group B
      consisted of elderly women. CONCLUSIONS: The findings from this magnetic
      resonance imaging study suggest that the degree of semispinalis cervics repair
      affects postoperative cervical alignment, and significant loss of cervical
      lordosis tends to occur in elderly women who undergo laminoplasty.

PMID- 11598513
TI  - Clinical outcome of trans-sacral interbody fusion after partial reduction for
      high-grade l5-s1 spondylolisthesis.
AB  - STUDY DESIGN: A clinical retrospective study was conducted. OBJECTIVE: To
      evaluate the clinical and radiographic outcome of reduction followed by trans
      sacral interbody fusion for high-grade spondylolisthesis. SUMMARY OF BACKGROUND
      DATA: In situ posterior interbody fusion with fibula allograft has improved the
      fusion rates for patients with high-grade spondylolisthesis. The use of this
      technique in conjunction with partial reduction has not been reported. METHODS:
      Nine consecutive patients underwent treatment of high-grade (Grade 3 or 4)
      spondylolisthesis with partial reduction followed by posterior interbody fusion
      using cortical allograft. The average age at the time of surgery was 27 years
      (range, 8-51 years), and the average follow-up period was 43 months (range, 24-72
      months). Before surgery, eight patients had low back pain, seven patients had
      radiating leg pain, and five patients had hamstring tightness. The average grade
      of spondylolisthesis by Meyerding grading was 3.9 (range, 3-5). Charts and
      radiographs were evaluated, and outcomes were collected by use of the modified
      SRS outcomes instrument. RESULTS: Radiographic indexes demonstrated significant
      improvement with partial reduction and fusion. The slip angle, as measured from
      the inferior endplate of L5, improved from 41.2 degrees (range, 24-82 degrees )
      before surgery to 21 degrees (range, 5-40 degrees ) after surgery. All the
      patients were extremely or somewhat satisfied with surgery. The two patients who
      underwent this operation without initial instrumentation experienced fractures of
      their interbody grafts. Both of these patients underwent repair of the
      pseudarthrosis with placement of trans-sacral pedicle screw instrumentation and
      subsequent fusion. CONCLUSIONS: Partial reduction followed by posterior interbody
      fusion is an effective technique for the management of high-grade
      spondylolisthesis in pediatric and adult patient populations, as assessed by
      radiographic and clinical criteria. Pedicle screw instrumentation with the sacral
      screws capturing L5 is recommended when this technique is used for the treatment
      of high-grade spondylolisthesis. According to the clinical and radiographic
      results from this study, partial reduction and posterior fibula interbody fusion
      supplemented with pedicle screw instrumentation is an effective technique for
      select patients with high-grade spondylolisthesis at L5-S1.

PMID- 11598514
TI  - Geometric torsion in idiopathic scoliosis: three-dimensional analysis and
      proposal for a new classification.
AB  - STUDY DESIGN: Three-dimensionally reconstructed spines of 62 subjects with
      idiopathic scoliosis were reviewed for three-dimensional pattern classification
      based on the measurement of geometric torsion. OBJECTIVES: To evaluate the
      relevance of geometric torsion as a three-dimensional index of scoliosis, and to
      develop a three-dimensional classification of deformity for idiopathic scoliosis
      as opposed to the current classifications based on two-dimensional frontal views.
      SUMMARY OF BACKGROUND DATA: Attempts have been made to measure the geometric
      torsional shape of scoliotic curves represented curvilinearly. However, the
      geometric torsion phenomenon has never been properly analyzed and thus has never
      been precisely defined. METHODS: Standardized stereoradiographs of 62 patients
      with idiopathic scoliosis were obtained and used to generate three-dimensional
      reconstructions. A continuous parametric form of the curved line that passes
      through the vertebrae was created by least square fitting of Fourier series
      functions. Frenet's formulas then were used to calculate the geometric torsion.
      RESULTS: Analysis of geometric torsion associated with 94 major scoliotic curves
      allowed three basic categories of torsion curve patterns to be identified.
      Scoliotic spines with multiple major curves are described by a combination of
      basic torsion patterns, one for each curve. CONCLUSIONS: A three-dimensional
      analysis of the spine in terms of geometric torsion has defined three distinct
      patterns of torsion in a group of scoliotic curves. Geometric torsion had extreme
      values at the levels of upper and lower vertebrae, but zero or nearly zero values
      at the levels of the apices. The torsional phenomenon can be unidirectional or
      bidirectional in both single and double major curves.

PMID- 11598515
TI  - Progression of vertebral and spinal three-dimensional deformities in adolescent
      idiopathic scoliosis: a longitudinal study.
AB  - STUDY DESIGN: The evolution of scoliotic descriptors was analyzed from three
      dimensionally reconstructed spines and assessed statistically in a group of
      adolescents with progressive idiopathic scoliosis. OBJECTIVES: To conduct an
      intrasubject longitudinal study quantifying evolution of two- and three
      dimensional geometrical descriptors characterizing the scoliotic spine and
      vertebral deformities. SUMMARY OF BACKGROUND DATA: The data available on
      geometric descriptors usually are based on cross-sectional studies comparing
      scoliotic configurations of different individuals. The literature reports very
      few longitudinal studies that evaluated different phases of scoliotic progression
      in the same patients. METHODS: The evolution of regional and local descriptors
      between two scoliotic visits was analyzed in 28 adolescents with scoliosis.
      Several statistical analyses were performed to determine how spinal curvatures
      and vertebral deformities change during scoliosis progression. RESULTS: At the
      thoracic level, vertebral wedging increases with curve severity in a relatively
      consistent pattern for most patients with scoliosis. Axial rotation mainly
      increases toward curve convexity with scoliosis severity, worsening the
      progression of vertebral body deformities. No consistent evolution is associated
      with the angular orientation of the maximum wedging. Thoracic kyphosis varies
      considerably among subjects. Both increasing and decreasing kyphosis are observed
      in nonnegligible proportions. A decrease in kyphosis is associated with a shift
      in the plane of maximum deformity toward the frontal plane, which worsens the
      three-dimensional shape of the spine. CONCLUSIONS: The results of this study
      challenge the existence of a typical scoliotic evolution pattern and suggest that
      scoliotic evolution is quite variable and patient specific.

PMID- 11598516
TI  - Surgical treatment of congenital kyphosis.
AB  - STUDY DESIGN: In this study, 26 cases of congenital kyphosis and kyphoscoliosis
      treated surgically were retrospectively reviewed. OBJECTIVE: To assess the
      clinical outcomes and surgical indications for posterior only versus
      anteroposterior surgery in the child. SUMMARY OF BACKGROUND DATA: Congenital
      kyphosis usually is progressive without surgical intervention. Current
      recommended treatment includes posterior arthrodesis for deformities of less than
      50 degrees to 60 degrees, and anterior release or decompression, anterior fusion,
      and posterior instrumented arthrodesis for large deformities and cord
      compression. METHODS: Cases involving myelodysplasia, spinal dysgenesis, and
      skeletal dysplasia were excluded from the study. Kyphoscoliosis was included if
      the kyphotic deformity was greater than the scoliotic deformity. Patients were
      grouped by age and surgical technique. The patients in group P1 underwent
      posterior arthrodesis at an age younger than 3 years, and those in group P2
      underwent the procedure at an age older than 3 years. The patients in group AP1
      underwent anterior and posterior procedures at an age younger than 3 years, and
      those in group AP2 underwent the procedures at an age older than 3 years. The
      preoperative deformity, complications, and postoperative deformity correction
      were analyzed. There were nine Type 1 (failure of formation), nine Type 2
      (failure of segmentation), and eight Type 3 (mixed) deformities. Four patients
      had associated spinal dysraphism. Three patients with Type 1 deformities had
      clinical or radiographic evidence of cord compression. RESULTS: In Group P1, five
      patients at an average age of 16 months underwent posterior arthrodesis alone for
      an average kyphotic deformity of 49 degrees. The immediate postoperative
      correction improved over a period of 6 years and 9 months by an additional 10
      degrees, resulting in a final deformity of 26 degrees. Pseudarthrosis developed
      in two patients, requiring fusion mass augmentation or anterior arthrodesis.
      Neither patient was instrumented. In Group P2, five patients at an average age of
      13 years and 7 months underwent posterior arthrodesis with instrumentation for
      kyphotic deformity of 59 degrees. Approximately 30 degrees of intraoperative
      correction was achieved safely using compression instrumentation and positioning.
      No further correction occurred with growth. The final residual kyphotic deformity
      was 29 degrees after a follow-up period of 4 years and 5 months. In Group AP1,
      seven patients underwent anterior release or vertebra resection for deformity
      correction and posterior arthrodesis for an average kyphotic deformity of 48
      degrees at the age of 16 months. There were no iatrogenic neurologic injuries.
      The final residual kyphotic deformity was 22 degrees after a follow-up period of
      6 years and 3 months. In Group AP2, nine patients underwent anterior release or
      decompression with posterior arthrodesis for kyphotic deformity of 77 degrees at
      the age of 11 years and 6 months. The deformity was corrected to 37 degrees, with
      no significant loss over a follow-up period of 5 years and 2 months. There were
      two postoperative neurologic complications. CONCLUSIONS: After reviewing their
      experience, the authors made the following observations: 1) The pseudarthrosis
      rate was low even without routine augmentation of fusion mass if instrumentation
      was used; 2) gradual correction of kyphosis may occur with growth in patients
      younger than 3 years with Types 2 and 3 deformities after posterior fusion, but
      appears to be unpredictable; 3) the risk of neurologic injury with anterior and
      posterior fusion for kyphotic deformity was associated with greater age, more
      severe deformity, and preexisting spinal cord compromise.

PMID- 11598517
TI  - The fate of autogenous free-fat grafts after posterior lumbar surgery: part 1. A
      postoperative serial magnetic resonance imaging study.
AB  - STUDY DESIGN: Time-related changes in free-grafted fat were investigated by
      postoperative serial magnetic resonance imaging in 22 patients with degenerative
      spinal disease who underwent posterior lumbar decompressive surgery. OBJECTIVES:
      To analyze the size and quality of the grafted fat on magnetic resonance imaging
      after posterior lumbar surgery. SUMMARY OF BACKGROUND DATA: Epidural fat grafts
      have been used to prevent epidural and perineural fibroses. Evaluations of
      changes in grafted fat have been reported, as observed on computed tomography
      scans. However, there are no published reports of clinical serial magnetic
      resonance imaging observations of grafted fat after posterior lumbar surgery.
      METHODS: Axial T1- and T2-weighted magnetic resonance imaging was performed at 3,
      7, 21, and 42 days as well as 1 year after surgery. The signal intensity of the
      fat was classified on the T1-weighted image as Grade 1 (almost equal to
      subcutaneous fat tissue), Grade 2 (low-signal intensity as compared with
      subcutaneous fat tissue), Grade 3 (speckled intensity), or Grade 4 (signal void,
      suggesting the change to scar tissue. The time-related, cross-sectional area of
      the subarachnoidal space was measured from the T2-weighted image. RESULTS: The
      size of the grafted fat was reduced to approximately 57% after 42 days, and to
      about 33% after more than 1 year, as compared with the condition 3 days after
      surgery. In time, the shape of the grafted fat was changed along the shape of the
      dura mater. During the early stage (within 6 weeks after surgery), the signal
      intensity of the grafted fat was lower than that of normal subcutaneous fat
      tissue (Grades 2-4: 40.9-59.1%). However, the intensity had recovered to normal
      status (Grade 1) by 1 year after surgery. CONCLUSIONS: The total amount of
      grafted fat used in posterior lumbar surgery is reduced. However, as observed on
      magnetic resonance imaging, it is alive and remodeled along the shape of the dura
      mater in relation to its shrinkage and reexpansion. This remodeling of the
      grafted fat is meaningful and effective in protecting the spinal nerve. This
      report clarifies the fate of the grafted fat from the findings of postoperative
      serial magnetic resonance imaging after lumbar decompressive surgery.

PMID- 11598518
TI  - The fate of autogenous free-fat grafts after posterior lumbar surgery: part 2.
      Magnetic resonance imaging and histologic studies in repeated surgery cases.
AB  - STUDY DESIGN: Histologic changes of free-grafted fat were investigated from
      surgical specimens taken at repeated lumbar surgery in 18 patients with
      degenerative spinal disease who previously had undergone posterior lumbar
      decompression and free fat graft. OBJECTIVE: To clarify the clinical usefulness
      of free-grafted fat by histologic analysis. SUMMARY OF BACKGROUND DATA: The
      clinical postoperative serial magnetic resonance imaging studies in Part 1 showed
      that the size of grafted fat was reduced, and that the shape changed along with
      the shape of the dura mater. The shape of the grafted fat was remodeled in
      relation to the postoperative transient shrinkage and reexpansion of the dura
      mater. METHODS: From repeated surgery cases, the status of the previously grafted
      fat tissue in the virgin operation was analyzed. Sections from the specimens
      resected surgically during repeated surgery were stained with hematoxylin and
      eosin or osmium. The size and quality of the grafted fat globules were analyzed
      by computer. RESULTS: In all cases, grafted fat tissue was identified as a
      survival. Hematoxylin and eosin staining showed increased collagen fiber and
      hyperplasia of blood vessels entering the fat tissue that survived. From osmium
      staining, the size of fat globules was reduced. The shape and quality of the fat
      globules were analyzed by original staging. They showed various sizes,
      polymorphism, and vacuolar degeneration. CONCLUSIONS: Finding showed that the
      grafted fat used in posterior lumbar surgery reduced the size and quality of the
      fat globules, as compared with normal fat tissue. However, the grafted fat
      tissues were confirmed to be alive over the long term. This study clarified the
      fate of the grafted fat as observed by magnetic resonance imaging and histology
      from repeated surgery cases.

PMID- 11598519
TI  - Health-related quality of life and somatization in patients with long-term low
      back pain: a prospective study with 109 patients.
AB  - STUDY DESIGN: For this study, a prospective cohort of 109 patients was recruited
      consecutively at an orthopedic inpatient unit of a university hospital. Three
      self-report instruments were administered to patients with sciatica believed to
      be caused by a herniated lumbar disc to examine their quality of life and psychic
      stress at baseline and at the 1-year follow-up visit. OBJECTIVES: To investigate
      whether patients who have undergone a previous discectomy experience greater
      psychic stress than patients with no surgery, and to determine whether the groups
      differed regarding their health-related quality of life at the follow-up visit.
      SUMMARY OF BACKGROUND DATA: Previous studies have described psychic abnormalities
      in patients with long-term back pain, particularly patients with severe
      chronicity (i.e., history of surgeries and persistent problems) or those who
      underwent a previous discectomy. Additionally, a series of studies has shown that
      psychic and psychosocial parameters exert a significantly greater influence on
      the success of treatment than do clinical and imaging findings or the extent of
      disc abnormality. METHODS: The Short Form Health Survey 36, the Symptom Checklist
      90, and Screening for Somatoform Disorders were administered to 109 patients
      consecutively treated in the authors' orthopedic university clinic, at baseline
      and at the 1-year follow-up visit. RESULTS: In all the patients examined, the
      physical and mental quality of life improved regardless of their group
      classification. The psychological distress, according to the Symptom Checklist
      90, was clearly reduced in both groups at the follow-up visit, with the exception
      of somatization, as indicated by Symptom Checklist 90 and Screening for
      Somatoform Disorders. Whereas the patients who had undergone surgery remained
      nearly unchanged with regard to their somatization, the patients with no previous
      surgery improved significantly, as indicated by Screening for Somatoform
      Disorders and Symptom Checklist 90. Somatization, particularly that surveyed by
      the comprehensive Screening for Somatoform Disorders, proved to be quite a
      stabile factor over time in both groups. The extent of the physical impairment
      before treatment was nearly the same in both groups, as indicated by Short Form
      Health Survey 36. Despite a markedly higher chronicity of reported problems,
      patients who had undergone surgery were hardly more greatly impaired in terms of
      their mental quality of life and psychological distress, as indicated by Symptom
      Checklist 90, than those without a history of surgery. At the follow-up visit,
      the differences tended to be minimal as well. As compared with those who had no
      previous surgeries, the patients who had undergone surgery were significantly
      more heavily impaired in their physical quality of life despite significant
      improvements. CONCLUSIONS: Patients with sciatica demonstrated less abnormality
      in terms of the psychopathologic markers investigated than described in previous
      studies. Nevertheless, the predisposition to somatize influences health-related
      quality of life to a high degree.

PMID- 11598520
TI  - Mobilization of patients after spinal surgery for acute spinal cord injury.
AB  - STUDY DESIGN: A retrospective review was conducted covering records of patients
      who underwent spinal surgery after acute spinal cord injury. OBJECTIVE: To study
      the relation between time of operation and mobilization of patients. SUMMARY OF
      BACKGROUND DATA: No such report has existed in the literature. METHODS: Reviews
      were conducted for the medical records of 102 consecutive patients with acute
      spinal cord injury admitted to the National Spinal Injuries Center whose spines
      had been stabilized surgically. The surgeries had been performed either in the
      National Spinal Injuries Center or in hospitals of the United Kingdom or
      Continental Europe not specialized in comprehensive care of spinal cord injury.
      For the patients in three groups, the date of operation and the date of
      mobilization were compared. The causes for delay in mobilization were identified.
      RESULTS: A trend of negative correlation was found between the mean number of
      days from injury to operation and the mean number of days from injury to
      mobilization. Conversely, a trend of positive correlation was found between the
      mean number of days from injury to admission or transfer to the National Spinal
      Injuries Center and the mean number of days from injury to mobilization. Long
      stay in bed was associated with complications. None of the patients in Group A
      stayed in bed longer than 77 days, whereas 13 patients in Groups B and C combined
      had a longer stay. The difference was statistically significant (P = 0.02, chi2).
      Eight of these patients had pressure sores. CONCLUSION: To ensure early
      mobilization, early spinal surgery must be supported by specialized comprehensive
      care.

PMID- 11598523
TI  - Transpedicular eggshell osteotomies for congenital scoliosis using frameless
      stereotactic guidance.
AB  - STUDY DESIGN: Three cases of multiplanar congenital scoliosis corrected by a
      transpedicular eggshell osteotomy using frameless stereotactic guidance are
      reported. OBJECTIVE: To show an alternative surgical technique for correcting and
      fusing complex congenital spinal curves. SUMMARY OF BACKGROUND DATA: Children
      with congenital scoliosis can have progressive curves causing significant
      multiplanar deformities. In older children, traditional approaches to spinal
      corrective surgery including fusion in situ, convex growth arrest, and
      hemivertebra excision can achieve only limited corrections. METHODS: Three older
      patients who had congenital scoliosis with significant multiplanar curves
      underwent one-stage posterior transpedicular eggshell osteotomy. Three
      dimensional reconstructive images and frameless stereotactic guidance were used
      for preoperative selection of osteotomy levels and accurate placement of pedicle
      screws. After completion of the osteotomy, closure was obtained with extension of
      the hips. RESULTS: The average coronal correction of the major curve was 28.7
      degrees (range, 22-33 degrees ). The average correction of the plumb line or
      lateral displacement from the center of the trunk was 4.8 cm (range, 3-7.5 cm). A
      significant kyphotic deformity was corrected 38 degrees, and a pelvic tilt was
      reduced from 7 to 3 cm. CONCLUSIONS: One-stage posterior reduction eggshell
      osteotomy can be used to correct a sagittal and/or coronal congenital spinal
      curve imbalance. Frameless stereotactic guidance for solid pedicle screw fixation
      was essential to the achievement of rigid spinal stabilization before
      arthrodesis. Transpedicular eggshell osteotomy is a technique that should be
      considered for older patients who have congenital scoliosis with multiplanar
      spinal abnormalities.

PMID- 11598522
TI  - Spinal lordosis with marked opisthotonus secondary to dystonia musculorum
      deformans: case report with surgical management.
AB  - STUDY DESIGN: A case report of severe spinal lordosis with marked opisthotonus
      and retrocollis secondary to dystonia musculorum deformans is presented.
      OBJECTIVE: To describe a case of dystonia musculorum deformans with progressive
      spinal lordosis and its surgical treatment. SUMMARY OF BACKGROUND DATA: Four
      patients with correction of coronal spinal deformity associated with dystonia
      musculorum deformans have been reported in the literature. No reports of sagittal
      spinal deformity treated with surgical instrumentation and fusion were found.
      METHODS: A retrospective chart and radiographic review of a single case was
      conducted. RESULTS: Orthotic management and pharmacologic therapy with botulinum
      toxin injections were unsuccessful in controlling the deformity. Severe spinal
      lordosis (170 degrees ) from occiput to sacrum was corrected surgically, allowing
      an upright posture. CONCLUSION: Dystonia musculorum deformans is a rare condition
      resulting in coronal or sagittal plane deformities. When other treatment methods
      are unsuccessful, surgical instrumentation and arthrodesis may correct the
      deformity and improve function.

PMID- 11598524
TI  - Possible use of arthrodesis for intractable sacroiliitis in spondylarthropathy:
      report of two cases.
AB  - STUDY DESIGN: Two cases of successful sacroiliac joint arthrodesis for medically
      intractable aseptic sacroiliitis are reported. SUMMARY OF BACKGROUND DATA:
      Although successful arthrodesis of the sacroiliac joint had been reported
      previously for septic sacroiliitis, no report had shown the procedure to be
      effective for spondylarthropathy. METHODS: Two women with spondylarthropathy
      involving very painful sacroiliac arthritis for 18 and 24 months had been
      relieved only transiently by several injections of steroids into the sacroiliac
      joint under fluoroscopy and by Bermuda casts. Both patients underwent sacroiliac
      joint arthrodesis. RESULTS: Both patients showed dramatic improvement after
      sacroiliac joint arthrodesis. Moreover, no relapses had occurred, respectively,
      after 2 and 3 years of follow-up evaluation despite continuing spondylarthropathy
      in other joints. CONCLUSIONS: After a careful selection of patients, including
      positive blocks in the sacroiliac joint, arthrodesis of sacroiliac joint might be
      considered for so-called "intractable" aseptic sacroiliitis.

PMID- 11598526
TI  - An electrophysiologic study of mechanoreceptors in the sacroiliac joint and
      adjacent tissues.
AB  - STUDY DESIGN: The somatosensory afferent units in the sacroiliac joint of an
      animal model were investigated using an electrophysiologic technique. OBJECTIVES:
      To identify the mechanosensitive receptive fields in the sacroiliac joint, and to
      determine their distribution and characteristics. SUMMARY OF BACKGROUND DATA: The
      sacroiliac joint is considered to be a source of lower back pain. Although there
      have been clinical studies on the diagnosis of sacroiliac joint pain, no
      satisfactory diagnostic method other than joint blocks has been reported. It
      still is not clear whether the sacroiliac joints actually transmit pain to the
      central nervous system. The sensory innervation of the sacroiliac joint has not
      been fully characterized neurophysiologically. METHODS: Experiments were
      performed on 10 adult cats weighing 2.6 to 4 kg. The animals were anesthetized
      with intravenous sodium pentobarbital. An L4-L7 laminectomy was performed. The L4
      L6 dorsal roots were cut at their proximal ends, split, and draped over a bipolar
      recording electrode. Glass probes were used to search the sacroiliac joint and
      adjacent tissues for mechanosensitive units. When units were identified, they
      were stimulated electrically to obtain conduction velocities and by Semmes
      Weinstein monofilaments to determine mechanical thresholds. RESULTS: In the
      sacroiliac joint and adjacent muscles, 29 discrete mechanosensitive units were
      identified. Of these 29 units, 26 were found in the posterior sacroiliac ligament
      and the remaining 3 in the adjacent muscles. Also, 16 units (55%) were identified
      in the proximal third of the sacroiliac joint. Conduction velocities of the units
      ranged from 3.1 to 22 m/second (average, 9.2 m/second), and 26 units were group
      III. Mechanical thresholds of the units ranged from 4.6 to 164.3 g (average, 69.7
      g). Whereas 28 units (96.6%) had thresholds higher than 7 g, one unit (3.4%) had
      a threshold lower than 7 g. CONCLUSIONS: Group III units with mechanical
      thresholds higher than 7 g may serve as nociceptors, and units with thresholds of
      lower than 7 g may serve as proprioceptors. The current study showed that most of
      the units in the sacroiliac joint were high-threshold group III units that
      perhaps had a nociceptive function. This result suggests that the sacroiliac
      joint may be a source of lower back pain in humans. This study also showed that
      the sacroiliac joint has little proprioceptive function.

PMID- 11598527
TI  - Analysis of the convergent and discriminant validity of published lumbar flexion,
      extension, and lateral flexion scores.
AB  - STUDY DESIGN: Articles reflecting the convergent or discriminant validity of the
      lumbar range of motion tests were reviewed and compared. Mean scores and standard
      deviations for lumber range of motion from healthy control subjects were plotted
      against those from patients with low back injuries. OBJECTIVE: To use published
      research to analyze the convergent and discriminant validity of lumbar range of
      motion tests for the characterization of low back pain and injury. SUMMARY OF
      BACKGROUND DATA: Several publications have addressed lumbar range of motion
      validity. Individual studies suggest that the tests possess convergent validity,
      but that their discriminant validity is indeterminate. METHODS: English-language
      journals were searched on Medline using "region," "lumbar," "range of motion,"
      "validity of results," "observer variation," and "low back pain" as title and
      subject search terms. The study methods approximating the specifications of the
      American Medical Association Guides to the Evaluation of Permanent Impairment
      were included in the analysis. RESULTS: Convergent validity research showed
      inconsistent relations between inclinometric and radiographic lumbar range of
      motion measurements. Some studies showed strong relation, whereas others showed
      essentially no relation between the two techniques. Correlations between lumbar
      range of motion scores and spinal disability and function were similarly
      inconclusive. Studies reporting mean scores and standard deviations for lumbar
      range of motion measurements showed a high degree of overlap between the scores
      of participants with low back injuries and those without such injuries.
      CONCLUSIONS: Convergent and discriminant validities of the lumbar range of motion
      tests currently require further substantiation. Absolute lumbar range of motion
      scores may not be suitable as the sole determinants of low back pathology
      diagnosis. Implications for using the lumbar range of motion tests to
      characterize low back injuries in medicolegal situations are discussed.

PMID- 11598528
TI  - Comparison of three manual coccydynia treatments: a pilot study.
AB  - STUDY DESIGN: A prospective pilot study with independent assessment and a 2-year
      follow-up period was conducted. OBJECTIVES: To compare and assess the efficacy of
      three manual coccydynia treatments, and to identify factors predictive of a good
      outcome. SUMMARY OF BACKGROUND DATA: Various manual medicine treatments have been
      described in the literature. In an open study, the addition of manipulation to
      injection treatment produced a 25% increase in satisfactory results. Dynamic
      radiographs of the coccyx allow breakdown of coccydynia into four etiologic
      groups based on coccygeal mobility: luxation, hypermobility, immobility, and
      normal mobility. These groups may respond differently to manual treatments.
      METHODS: The patients were randomized into three groups, each of which received
      three to four sessions of a different treatment: levator anus massage, joint
      mobilization, or mild levator stretch. Assessment with a visual analog scale was
      performed by an independent observer at 7 days, 30 days, 6 months, and 2 years.
      RESULTS: The results of the manual treatments were satisfactory for 25.7% of the
      cases at 6 months, and for 24.3% of the cases at 2 years. The results varied with
      the cause of the coccydynia. The patients with an immobile coccyx had the poorest
      results, whereas those with a normally mobile coccyx fared the best. The patients
      with luxation or hypermobility had results somewhere between these two rates.
      Levator anus massage and stretch were more effective than joint mobilization,
      which worked only for patients with a normally mobile coccyx. Pain when patients
      stood up from sitting and excessive levator tone were associated with a good
      outcome. However, none of the results was significant because of the low success
      rate associated with manual treatment. CONCLUSIONS: There is a need for a placebo
      controlled study to establish conclusively whether manual treatments are
      effective. This placebo must be an external treatment. A sample size of 190
      patients would be required for 80% confidence in detecting a difference.

PMID- 11598530
TI  - Lumbar cauda equina syndrome associated with the use of gelfoam: case report.
AB  - STUDY DESIGN: A case of cauda equina syndrome is reported. OBJECTIVE: To
      recognize a serious complication related to the use of Gelfoam in the lumbar
      spine. SUMMARY AND BACKGROUND DATA: Absorbable hemostatic gelatin sponges have
      long been used to control bleeding around the spinal cord. Despite widespread use
      and a safe history with few reported adverse reactions, Gelfoam sponges have
      potential for complications that may be overlooked. METHOD: A case of cauda
      equina syndrome is reported and discussed. RESULTS: A retained Gelfoam sponge was
      found in the epidural space after lumbar decompression and fusion for spinal
      stenosis. The retained gelatin sponge had expanded and solidified, causing a mass
      affect. The resultant nerve compression led to progressive myelopathy. On removal
      of the Gelfoam, symptoms rapidly resolved. CONCLUSIONS: Although the use of
      Gelfoam in spine surgery generally is considered safe, care must be taken to
      avoid placing a large mass of sponge in a potentially closed space. If Gelfoam is
      not handled properly, it can engorge and fail to be resorbed appropriately, thus
      causing a mass effect. If neurologic compromise develops, Gelfoam should be
      considered a potential cause and subsequently removed.

PMID- 11598531
TI  - Idiopathic herniation of the thoracic spinal cord: report of three cases.
AB  - STUDY DESIGN: Cases are reported and the literature is reviewed. OBJECTIVE: To
      present three cases involving idiopathic herniation of the thoracic cord. SUMMARY
      OF BACKGROUND DATA: Idiopathic spinal cord herniation is a very rare condition.
      Only 20 cases have been reported. The radiographic and intraoperative findings
      concerning this herniation remain insufficient, and its pathophysiology is less
      understood. METHODS: Idiopathic herniation of the thoracic spine was managed
      operatively in the three cases. The clinical, radiologic, and intraoperative
      features in these cases are described, and the pathophysiology of this disorder
      is discussed from a review of the literature. RESULTS: Two of the three patients
      had a defect in the inner layer of the duplicated ventral dura mater through
      which the spinal cord was herniated. The third patient had a ventral epidural
      cyst into which the spinal cord had protruded. Operative reduction of the spinal
      cord improved motor power in all three patients, although sensory disturbance
      remained unchanged. CONCLUSIONS: There should be several types of idiopathic
      spinal cord herniation. This is the first report of this herniation that focuses
      the abnormalities of the ventral dura mater, together with image and
      intraoperative findings.

PMID- 11598533
TI  - [Ambiguous relationships between vascular thrombosis and Crohn's disease: cause
      or marker? ].

PMID- 11598534
TI  - [Factors associated with hyperhomocysteinemia in Crohn's disease].
AB  - AIMS: The incidence of thromboembolic disease is increased in patients with
      inflammatory bowel disease. Hyperhomocysteinemia is one of the risk factors for
      thrombosis. The aims were: 1) to assess the prevalence of hyperhomocysteinemia in
      a large series of patients with Crohn's disease; 2) to search for clinical and
      biological factors associated with hyperhomocysteinemia. PATIENTS AND METHODS:
      One hundred seventy-one patients with Crohn's disease (64 males, 107 females),
      median age 31 years (range: 16-82), were studied. The median duration of the
      disease was 7 years. The concentrations of homocysteine, folate, cobalamin and C
      reactive protein were measured in serum from blood sample of each patient.
      RESULTS: The mean concentration of seric homocysteine was 14.8 micromol/L (N: 4.4
      - 12.4 micromol/L). Hyperhomocysteinemia was observed in 89 patients (52%). It
      was significantly associated with age, sex, smoking habit, serum cobalamin level
      and history of ileal surgical resection (P<0.05). In the group of operated
      patients, there was a statistically significant association between
      hyperhomocysteinemia and the length of small bowel resected. In multivariate
      analysis, sex and smoking were associated with hyperhomocysteinemia. CONCLUSION:
      More than half of the patients with Crohn's disease have hyperhomocysteinemia.
      This result stresses the need for preventing reversible factors associated with
      hyperhomocysteinemia, such as smoking and cobalamin deficiency, in order to lower
      the thrombotic risk of patients with Crohn's disease.

PMID- 11598536
TI  - [Role of remaining ductal cephalad obstruction on the results of lateral
      pancreaticojejunostomy in chronic pancreatitis].
AB  - AIMS: To report the results of a pancreaticojejunostomy in the treatment of
      chronic pancreatitis, and to assess the role of residual cephalic ductal
      obstruction in pain recurrence. METHODS: Thirty seven patients with painful
      chronic pancreatitis whose pancreatic duct diameter exceeded 6 mm were treated by
      lateral pancreaticojejunostomy and were retrospectively studied. Deobstruction of
      the cephalad portion of the main pancreatic duct was complete in 21 patients
      (group A), while residual obstruction was noted in 16 patients (group B).
      RESULTS: One patient died post-operatively (2.7%) and 6 patients underwent
      complications (16%) that were treated without reoperation. With a median follow
      up of 52 months, 26 patients were pain free (70%). Pain recurrence occurred in 3
      patients in group A (14%) who were treated medically, versus in 8 patients in
      group B (50%) of whom 4 needed iterative surgery. Ongoing alcoholic addiction did
      not influence pain recurrence, which onset significantly altered the weight
      increase observed after pancreaticojejunostomy. CONCLUSION: Lateral
      pancreaticojejunostomy has a low morbidity rate and offers long lasting pain
      relief in 86% of patients whose cephalad main pancreatic duct is completely
      deobstructed.

PMID- 11598535
TI  - [Assessment of the cost of first line chemotherapy in metastatic colorectal
      cancer. Preliminary results in the FFCD 9601 trial].
AB  - AIM: The objective of the study was to estimate the cost of first line
      chemotherapy in metastatic colorectal cancer treated in the Gustave-Roussy
      Institute. Patients were randomized in the study FFCD 9601 with four schedules of
      treatment: Tomudex(R), 5FU weekly, LV5FU2 with low dose of folinic acid and
      LV5FU2 with high dose of folinic acid. PATIENTS AND METHODS: Thirty three
      patients were included prospectively from March 1997 to April 1999. Healthcare
      costs took into account drug-regimen related costs (cost of the drugs and its
      preparation, drug administration, laboratory tests, transport from and to
      hospital), non-drug-regimen related hospitalization costs (treatment of
      chemotherapy related side effects, radiologic tests, hospital outpatient visits,
      transport from and to hospital) and surgery costs. Costs were derived from the
      accounting system in the Gustave-Roussy Institute. Non medical costs were not
      taken into account in this study. RESULTS: The median overall cost per 4 weeks
      was 6,343 FF with LV5FU2 low dose, 9,968 FF with LV5FU2 high dose, 15,340 FF with
      5FU weekly and 28,810 FF with Tomudex(R). This overcost is explained by a more
      expensive price and greater toxicity: 12 grade 3-4 toxicity and 9
      hospitalizations (including one in intensive care unit for the 8 treated
      patients) for Tomudex(R) despite a lower cost for the administration of the drug.
      Weekly 5FU was the most expensive among the 5FU schedules because of its dose and
      frequency of administration. CONCLUSIONS: The cost of first line chemotherapy in
      metastatic cancer colorectal is high (6,000 FF minimum per 4 weeks of treatment).
      Tomudex, a recent and expensive drug, seems to be more toxic. In this study,
      toxicity was probably overestimated due to the small number of patients. More
      patients are necessary in order to better estimate the cost of toxicity of these
      chemotherapies.

PMID- 11598537
TI  - [Clinical relevance of interleukin-18 production in the intestinal mucosa].

PMID- 11598538
TI  - [Adult to adult living related liver transplantation].

PMID- 11598539
TI  - [Adult to adult living-related liver transplantation. The Paul-Brousse Hospital
      preliminary experience].
AB  - AIM: Liver-graft shortages justify the development of adult living-related liver
      transplantation. The preliminary experience with this technique at Paul-Brousse
      Hospital is reported. PATIENTS ET METHODES: From January to July 2000, 7 adult to
      adult living-related liver transplantations were performed. Donors were 5 females
      and 2 males aged 20 to 53 years old (median: 41). A right liver graft was
      harvested in all cases. Recipients were 5 males and 2 females aged from 17 to 58
      years old (median: 50) transplanted for viral cirrhosis (4 cases including 2 with
      hepatocellular carcinoma), subfulminant hepatitis (1 case), hepatocellular
      carcinoma on a healthy liver (1 case), and epithelioid hemangioendothelioma (1
      case). Follow-up ranged from 41 to 157 days (median: 117 days). RESULTS: One
      donor had a biliary fistula that healed spontaneously. One donor had asterixis
      for 24 hours. The 7 donors are alive at home without any late complications. One
      recipient was retransplanted for hepatic artery thrombosis and 2 recipients had a
      biliary fistula that healed spontaneously. The 7 recipients are alive at home
      with normal liver function. CONCLUSION: Our experience and other reports suggest
      that adult to adult living-related liver transplantation is feasible with rare
      mortality and low morbidity in donors. Results in recipients are comparable to
      those obtained with cadaveric grafts. For a given patient the possibility of
      living related donation might extend the indications for transplantation without
      penalizing patients waiting for a cadaveric graft.

PMID- 11598542
TI  - [Esophagitis secondary to jejuno-esophageal reflux after total gastrectomy and
      Roux-en-Y loop].
AB  - We report a case of esophagitis secondary to jejuno-esophageal reflux after total
      gastrectomy and 60 cm Roux-en-Y jejunal loop. Both esophagitis and jejuno
      esophageal reflux disappeared after lengthening of the Y-loop by 50 cm.

PMID- 11598540
TI  - [Carbohydrate metabolism in cirrhosis].

PMID- 11598543
TI  - [Diclofenac-induced colitis complicated by Klebsiella oxytoca infection].
AB  - A 25-year-old man presented with abdominal pain and bloody diarrhea. Colonoscopy
      showed hemorrhagic proctocolitis with superficial erosions. Histology was
      consistent with the diagnosis of ulcerative colitis and biopsy cultures were
      negative. Despite treatment with prednisolone (40 mg/day), his clinical condition
      deteriorated and he was referred to our institution. On repeated questioning, the
      patient reported self-medication with diclofenac (200 mg/day) for 6 weeks to
      treat tendinitis prior to the beginning of digestive symptoms. Rectosigmoidoscopy
      confirmed bleeding colitis and repeated biopsy cultures showed Klebsiella
      oxytoca. Corticosteroids were stopped and ofloxacin (400 mg/day) was prescribed
      for 14 days. Diarrhea quickly resolved. Colonoscopy 8 weeks later showed only
      patchy erythematous mucosa without bleeding or erosions. Two years later, the
      patient remains asymptomatic with normal total colonoscopy. The definitive
      diagnosis was de novo NSAID-induced colitis subsequently complicated by
      Klebsiella oxytoca infection.

PMID- 11598544
TI  - [Complicated polycystic liver disease with intracystic hemorrhage and obstructive
      jaundice].
AB  - Polycystic liver disease, which is generally part of the autosomal dominant
      polycystic kidney disease, is often asymptomatic. We report a case of obstructive
      jaundice caused by compression of the biliary tract by a large haemorrhagic liver
      cyst. The patient was a man with sporadic polycystic liver disease without
      polycystic kidney disease and with normal renal function for his age. Ultrasound
      combined with cholangio-MRI provided non-invasive confirmation of intracystic
      bleeding and intrahepatic biliary dilatation. Obstructive jaundice was confirmed
      by cyst puncture-aspiration which resolved symptoms and normalized biology. The
      initial treatment of haemorrhagic liver cyst complicating polycystic liver
      disease must be medical with cyst aspiration-drainage and sclerotherapy to avoid
      surgery in these fragile patients.

PMID- 11598545
TI  - [Is cystic fibrosis an underreported cause of rectal prolapse in adults? ].

PMID- 11598546
TI  - [Anal ulceration caused by a cholesterol crystal embolus].

PMID- 11598547
TI  - [Management of megaduodenum].

PMID- 11598548
TI  - [Coronary insufficiency after an oral intake of capecitabine].

PMID- 11598549
TI  - [Clostridium difficile reactive arthritis].

PMID- 11598550
TI  - [Acute intermittent porphyria revealed by a paradoxical reaction to a
      benzodiazepine].

PMID- 11598551
TI  - [Anemia: a new cause of portal vein thrombosis? ].

PMID- 11598552
TI  - [Is Exolise hepatotoxic?].

PMID- 11598553
TI  - [Non-stop workshifts for hospital gynecologists-obstetricians?].

PMID- 11598556
TI  - [Birth mortality and pregnancy terminations: how can collected Diagnosis Related
      Group System data be used?].
AB  - In France since 1995, information on diagnoses and care are routinely collected
      for each patient hospitalised in a public or private hospital, using the
      Diagnosis Related Group system. Information on birth events constitutes a good
      example of possible use of this information for other aims than economic activity
      evaluation. In this paper, in order to highlight possible epidemiological use,
      some recommendations are proposed for collecting data on stillbirths and
      pregnancy terminations. The lack of usual knowledge on these two adverse events
      is the reason for this choice. While the improvements in prenatal diagnosis lead
      to an increase in pregnancy terminations, a minimum common core of collected data
      should allow routine epidemiological monitoring of these adverse perinatal
      events.

PMID- 11598554
TI  - [Acute fetal distress].
AB  - Three different clinical patterns of acute fetal distress may be observed during
      labor: an ante-partum hypoxia with a persistent nonreactive and "fixed" fetal
      heart rate (FHR) on admission to the hospital, a progressive intra-partum
      asphyxia manifested, as the labor continues, by a substantial rise in baseline
      heart rate, a loss of variability and repetitive severe variable or late
      decelerations, and finally, as a result of a catastrophic event, a sudden
      prolonged FHR deceleration to approximately 60 beats per minute lasting until
      delivery. However the majority of fetuses with nonreassuring tracings of FHR are
      neurologically intact, as evidenced by the high false-positive rate of electronic
      fetal monitoring (EFM). Therefore the diagnosis of fetal distress must be
      corroborated by complementary methods, such as continuous recording of the fetal
      electrocardiogram or computed-assisted EFM, fetal pulse oximetry or fetal scalp
      sampling with immediate determination of blood gases or lactates. Defavorable
      outcome of an acute fetal distress leading to neonatal encephalopathy or death is
      best predicted by a persisting low Apgar score (<3) for more than 5 minutes and
      by a severe metabolic acidosis (umbilical artery pH<7,00 and base-excess>
      12mmol/l).

PMID- 11598557
TI  - [Oxytocin and misoprostol administered intravaginally for termination of
      pregnancy at 13 to 29 weeks of amenorrhea. A prospective randomized trial].
AB  - OBJECTIVE: To compare the effectiveness of misoprostol administrated
      intravaginally alone versus misoprostol with oxytocin infusion for termination of
      pregnancy at 13 to 29 weeks. Subjects and methods. Ninety women at 13-29 weeks
      requesting pregnancy termination were randomized to receive 200 microgram of
      misoprotol intravaginally every 12 hours either with oxytocin infusion or alone
      for up to 48 hours. RESULTS: The mean induction to abortion interval was
      significantly shorter in the misoprostol-oxytocin group than in the misoprostol
      alone group (22+/-10.8 hours versus 27+/-14.1 hours respectively p<0.05). The 48
      hours successful abortion rates were 95% and 90% respectively. Abortion was
      complete in 79.1% and 62.5% respectively. Side effects were similar between
      groups. CONCLUSION: Vaginal misoprostol associated with oxytocin infusion is more
      effective than misoprostol alone in termination of second-trimester pregnancy.

PMID- 11598558
TI  - [Factors associated with cesarean section in France. Results from the 1995
      National Perinatal Survey].
AB  - OBJECTIVE: to study the relationship between the cesarean section rates and the
      characteristics of newborns, mothers and maternity units, studying primary and
      repeat cesarean sections, and cesarean sections before and during labour
      separately. Population. Representative sample of births in France. METHOD:
      Univariate and multivariate analyses. RESULTS: The primary cesarean section rate
      (among women without previous cesarean section) was 11.0% and the repeat cesarean
      section rate was 62.9%. The main factors associated with primary cesarean
      sections were breech presentation, small-for-gestational age before term, and
      high birthweight, for characteristics of newborns, and parity 0,30 years old or
      more and high pre- pregnancy weight, for characteristics of mothers. These
      factors were linked to cesarean sections before labour and during labour. Preterm
      and post-term deliveries, educational level, and nationality played a different
      role before and during labour. Very few factors were linked to repeat cesarean
      sections. CONCLUSION: Various factors are associated with cesarean sections; they
      express the influence of both unfavorable medical conditions and particular
      medical care organisations.

PMID- 11598559
TI  - [Physiology of stress urinary incontinence: a new theory based on the physical
      analysis of forces and anatomy].
AB  - We developed a theoretical model to understand the extrinsic factors of the
      bladder-urethral system involved in stress urinary incontinence and their
      relationships with cystocele or the protective effect of dorsal decubitus and
      with overfilled-bladder-related dysuria. The model is based on known physical
      rules (elasticity, pressure-volume relationships in a closed cavity - vagina and
      its supportive tissue, Retzius space) applied to anatomy. The anterior vaginal
      wall, divided in two parts, plays a major role in stress urinary incontinence by
      moderating the rise in the abdominal pressure on the bladder and also by
      increasing the pressure in the Retzius space that increases the resistance to
      flow in the urethra. The tent canvas hypothesis applied to the anterior portion
      of the vaginal wall under the urethra explains the relationship between defective
      vaginal wall resistance and mobility of the urethra-bladder junction.

PMID- 11598560
TI  - [ Ambulatory laparoscopic gynecological surgery in Africa: feasibility].
AB  - We report a prospective survey conduced between March 1998 and February 1999
      among 100 women classes ASA I and II who underwent laparoscopic surgery for
      gynecological disorders under general anesthesia. Among these laparoscopies 85
      (85%) were performed for operative purposes and 12 (10.7%) for diagnostic
      purposes. Minimal monitoring was used (no capnography) so prophylacti fluid
      loading with 0.9% saline was used before insufflation to reduce hemodynamic
      changes induced by abdominal overpressure and to avoid potential massive air
      embolism. Insufflation pressure was limited to 14 mmHg. The main agent used for
      all procedures was propofol. Mean duration of the procedures was 55 minutes.
      There were no cases of complications or delayed recovery. Complete exsufflation
      by abdominal compression at the end of the procedures induced minimal abdominal
      pain and scapulalgia. Ketoprofen as effective postoperatively. Twenty-five
      patients (25%) complained of nausea and vomiting in the recovery room and were
      treated effectively with metoclopramide. All patients were discharged and
      accompanied to their home six hours later after a well-tolerated light meal. The
      postoperative course was uneventful.

PMID- 11598561
TI  - [An ischemic pulmonary malformation of the surviving fetus occurring after
      selective embryo reduction in bichorionic pregnancy. Report of one case and
      literature review].
AB  - We describe, to our knowledge, the first case of a pulmonary malformation called
      acinar dysplasia occurring at a surviving fetus after selective embryo reduction
      in a bichorionic pregnancy. The chronological and histological observations
      suggest that this anomaly may be linked with a feticide achieved at 13 week's
      gestation. Literature review concerning selective embryo reduction shows rare
      cases of vascular connections in bichorionic pregnancies especially during the
      first half of gestation, that can explain in part the apparition of survivor's
      anomalies.

PMID- 11598562
TI  - [Metrorrhagia during the third trimester disclosing Munchausen syndrome].
AB  - Metrorrhagia during the third trimester of pregnancy similar to that observed in
      placenta praevia may be a signal to the physician that the patient is calling for
      help. This clinical situation is one where the patient mimics an illness, playing
      the role of a patient. The risk is that an unnecessary surgical procedure may be
      triggered, in this case cesarean section. The main difficulty in caring for these
      patients is to make the diagnosis. Treatment relies on psychotherapy which can
      contribute to an improved mother-infant relationship and perhaps prevent acts of
      self-mutilsation.

PMID- 11598564
TI  - To get involved or not--that is the question.

PMID- 11598563
TI  - [Removal or conservation of ovaries during hysterectomy for benign lesions].
AB  - At the time of hysterectomy, the aging ovary presents a dilemma. We conducted a
      prospective study to assess the feasibility of systematic oophorectomy in women
      50 years or older and a retrospective study of hysterectomy history in patients
      who developed cancer of the ovary. Our finding and data in the literature point
      out the requirement for careful assessment of two aspects of the problem, one
      technical (feasibility of adnexectomy) and the other functional (ovary function
      and risk of cancer on the retained ovary).

PMID- 11598565
TI  - Beam geometry and localization of structures.

PMID- 11598566
TI  - Two cases of unusually heavy odontolithiasis--one causing trismus.

PMID- 11598567
TI  - Endodontic culture.

PMID- 11598568
TI  - Whitish lobulated tumor of the tongue.

PMID- 11598569
TI  - Prevalence of cervical spine injuries in patients with facial trauma.
AB  - OBJECTIVE: Injuries to the spine may accompany facial trauma. By using a large
      computerized database the goal of this case control study was to assess the
      association between facial and cervical spine injuries among patients sustaining
      facial trauma. STUDY DESIGN: During a period of 4 years (1995 to 1998) 3083
      patients, 10 years or older, with facial injuries were admitted to the University
      Hospital of Innsbruck's Department of Oral and Maxillofacial Surgery for facial
      trauma. Records were analyzed for cause of injury, age and gender distribution,
      frequency and type of injury, and frequency of cervical spine injuries in
      relation to facial trauma and concomitant injuries. Two hundred six (6.7%) of
      these patients had experienced a concomitant cervical spine injury (case group).
      All other patients (2877) were assigned to the control group of facial trauma
      only. RESULTS: Facial trauma patients with concomitant cervical spine injuries
      were significantly older (mean age, 42 vs 34 years); no difference existed for
      the female/male ratio of 30:70. Sports trauma was the main cause of facial trauma
      in the control group (37.4%), yet traffic accidents accounted for 43.7% of
      combined facial and cervical spine injuries in the case group. Central mid face
      fractures dominated in the case group and lateral mid face fractures in the
      control group. In the case group cervical spine fractures and dislocations
      occurred in 19.2%. None of them showed evidence of paralysis. Concomitant brain
      injuries occurred in 21.6% of the case group and 8.8% of the control group. For
      patients sustaining facial trauma, logistic regression analysis revealed reduced
      risks for additional cervical spine injuries in younger patients, female
      patients, absence of brain injury, and in patients with facial soft tissue
      lesions alone (58.2%) or dental trauma alone (77.5%). CONCLUSION: The results of
      this study underline the importance of proper clinical and computed tomographic
      evaluation in cases of facial fractures for recognition of additional cervical
      spine trauma. Detection of cervical spine trauma can be missed, especially when
      pain or symptoms from other parts of the body dominate. The typical patient with
      concomitant neck and facial trauma is male, 40 years old, and usually involved in
      a traffic accident.

PMID- 11598570
TI  - Inferior alveolar nerve damage after lower third molar surgical extraction: a
      prospective study of 1117 surgical extractions.
AB  - PURPOSE: The purpose of this study was to determine the incidence of inferior
      alveolar nerve (IAN) damage after surgical removal of lower third molars, to
      identify the causes, and to construct a predictive model to assess the risk of
      IAN injury. STUDY DESIGN: We performed a nonrandomized forward prospective study
      of 946 consecutive outpatients subjected to surgical extraction of 1117 lower
      molars in the University of Barcelona Oral Surgery Department. Preoperative,
      intraoperative, and postoperative data were gathered, and suspected causal
      factors of IAN damage were identified by using nonparametric tests, the Pearson
      chi-square test, and the Fisher exact test. Logistic regression predicted the
      risk of IAN injury. RESULTS: Although only 1.3% of the extractions caused
      temporary nerve damage, 25% of the lesions were permanent. All of the following
      significantly increased the risk of IAN damage (P < .05): age, the radiologic
      relationship between the apices and the mandibular canal, deflection of the root
      when approaching the mandibular canal, distal ostectomy, the distance of the
      apices of the third molar to the mandibular canal, ostectomy, crown sectioning,
      pain during root luxation, primary closure of the wound, prolonged operating
      time, bleeding, exposure of the nerve, and postoperative ecchymosis. The first 4
      factors were included in a predictive logit model. CONCLUSIONS: Patient age,
      ostectomy of the bone distal to the third molar, the radiologic relationship
      between the roots of the third molar and the mandibular canal, and deflection of
      the mandibular canal increased the risk of IAN damage. Older patients were at a
      higher risk for suffering permanent injuries.

PMID- 11598571
TI  - Substance P and mast cells: preliminary histologic analysis of the human
      temporomandibular joint.
AB  - PURPOSE: Neuropeptide-containing nerves can serve as a mechanism for nervous
      system regulation of host defense responses. Because bacteria associated with
      reactive arthritis have been identified in the temporomandibular joint (TMJ),
      this study investigates whether the presence of substance P (SP) neuropeptide
      containing nerves and mast cells can be identified in the TMJ. MATERIAL AND
      METHODS: Posterior bilaminar tissue removed during TMJ surgery from 9 women was
      evaluated for the presence of neuropeptide-containing nerves by staining with a
      monoclonal antibody to SP. Staining of the TMJ tissue sections with 0.5%
      toluidine blue was performed to identify the presence of mast cells. RESULTS: SP
      containing nerves and mast cells were identified within the posterior bilaminar
      tissue associated with the vasculature. CONCLUSIONS: The presence of neuropeptide
      nerves and mast cells within the TMJ has been shown. Mast cell degranulation
      products and SP release can contribute to TMJ inflammation.

PMID- 11598572
TI  - Autologous blood injection for treatment of recurrent temporomandibular joint
      dislocation.
AB  - OBJECTIVE: The purpose of this study was to reintroduce a rather simple, safe,
      minimally invasive, and rapid alternative procedure for the treatment of
      recurrent dislocation of the condyles. STUDY DESIGN: Subjects were 3 patients (5
      joints) who suffered from recurrent condyle dislocation. The technique consisted
      of visually identifying a line from tragus to the eye angle. Then the articular
      fossa point was identified in this line, 10 mm anteriorly to tragus and 2 mm
      below the line. A 19-gauge needle was inserted at the articular fossa point.
      After injection of saline in the superior compartment, 5 cc of autologous blood
      drawn from the cubital fossa was injected (4 cc in the superior compartment and 1
      cc in the pericapsular tissue). After this an elastic bandage was applied and
      left for the first 24 hours. Patients were advised to constrain their mandibular
      motion and to eat only soft foods for a week. They received cephalosporin
      antibiotics and nonsteroidal anti-inflammatory drugs for 7 days. A week after the
      procedure, supervised physiotherapy was started and the patients were encouraged
      to increase their mandibular opening to 40 mm. RESULTS: Postoperative recoveries
      were uneventful. Dislocation of condyles did not reoccur; however, patient no. 3
      experienced an episode of unilateral subluxation. At follow-up all patients
      presented with normal mouth opening. CONCLUSION: Bleeding resulted from the
      introduction of a needle for injection in the pericapsular tissue. Blood coming
      from this wound, associated with autologous blood injected in the superior
      compartment, generates a bed for fibrous tissue formation in the region, creating
      a limitation of mandibular movement, thus ceasing dislocation of the condyles.
      Temporomandibular joint autologous blood injection is a simple procedure
      performed on an outpatient basis that we advise as an alternative treatment for
      patients with recurrent dislocation of the condyles.

PMID- 11598573
TI  - Treatment of chronic osteomyelitis in Korea.
AB  - OBJECTIVE: We sought to investigate the clinical and histopathologic features of
      chronic osteomyelitis and its treatment in Koreans. STUDY DESIGN: A total of 49
      patients (ages 11-79 years; mean, 47.3 years) were examined in this retrospective
      chart review. In a new treatment protocol used for 39 patients, chronic
      osteomyelitis of the jaws was treated by surgical intervention and 2 weeks of
      intravenous antibiotics, followed by 6 weeks of oral antibiotics, whereas a
      control group consisting of 10 patients was treated by surgery alone. Surgical
      therapy consisted of decortication or sequestrectomy and saucerization of the
      affected bone. A successful outcome was defined as the resolution of symptoms
      after surgery alone or after surgery and 8 weeks of antibiotic therapy. Failure
      was defined as a case requiring a second operation and 8 additional weeks of
      antibiotic therapy. RESULTS: A successful outcome was seen in 94.9% of patients
      on the new treatment protocol, as well as in 60% of control patients. A purulent
      discharge developed in 2 cases after the new treatment protocol and in 4 control
      cases, but the patients were treated successfully with a second operation.
      CONCLUSIONS: Surgery followed by antibiotic therapy for at least 8 weeks is an
      effective method for treating chronic osteomyelitis of the jaws.

PMID- 11598574
TI  - Selective COX-2 inhibitors: a review of their therapeutic potential and safety in
      dentistry.
AB  - Anti-inflammatory analgesics are commonly used medications in dental and medical
      practice. Their uses in dentistry include use as analgesics and as anti
      inflammatory agents. In addition, antipyretic action accompanies the medication.
      The action of these groups of drugs depends on the dose provided. Analgesic and
      antipyretic effects occur at low dose, whereas analgesic effects occur at high
      dose. Among the common side effects of this class of medications are
      gastrointestinal irritation with potential for ulceration, increased tendency for
      bleeding due to antiplatelet effects, and long-term chronic dosing effects on
      renal function may occur. Recent developments in the anti-inflammatory group of
      medications include the introduction of cyclooxygenase-II inhibitors. These
      agents offer potentially significant advantages because of their relative lack of
      gastrointestinal irritation. Because of this, it is likely that these medications
      will be frequently used in the management of dental and medical conditions.
      Patients will present while on these medications, and these agents may serve as
      medications for management of dental pain, postsurgical pain, and for anti
      inflammatory effects. The current literature indicates that COX-2 inhibitors
      offer substantial benefits because of their favorable gastrointestinal profiles
      and because of their lack of effect on platelet function.

PMID- 11598575
TI  - Orofacial pain, jaw function, and temporomandibular disorders in women with a
      history of juvenile chronic arthritis or persistent juvenile chronic arthritis.
AB  - OBJECTIVES: We sought to study the long-term outcome of juvenile chronic
      arthritis (JCA) in the temporomandibular joint (TMJ). STUDY DESIGN:
      Temporomandibular disorders, including TMJ involvement, were assessed in 42 women
      with pauciarticular or polyarticular JCA--on average 25.8 years from disease
      onset--and compared with those found in matched control subjects. Disease-related
      parameters associated with temporomandibular disorders were identified. RESULTS:
      The TMJ was involved in 66.7% of the patients, most severely in extended
      pauciarticular JCA. Temporomandibular disorders were more frequent in the
      patients than in the control subjects, especially in those with persistent
      disease. The TMJ involvement was positively correlated with disease duration and
      negatively correlated with jaw opening and occlusal support. Duration of active
      JCA and history of functional pain were identified as predictors of present TMJ
      involvement. CONCLUSION: In a long-term follow-up, TMJ involvement proved
      frequent in the studied patients and was associated with long disease duration
      and previous pain on jaw opening. The findings suggest that patients with JCA
      should undergo orofacial evaluation on a regular basis.

PMID- 11598576
TI  - Oral and craniofacial findings in Fabry's disease: a report of 13 patients.
AB  - OBJECTIVE: Fabry's disease is an X-linked metabolic disease caused by the
      deficiency of the lysosomal enzyme alpha-galactosidase A. The purpose of this
      study was to assess oral and craniofacial findings in a cohort of patients with
      Fabry's disease to facilitate recognition of this condition and early treatment
      of its manifestations. STUDY DESIGN: This is a case series describing oral and
      craniofacial findings of 13 male patients diagnosed with Fabry's disease. Data
      were collected by means of a standardized questionnaire, clinical examination,
      panoramic and cephalometric radiographs, and magnetic resonance imaging. RESULTS:
      A variety of abnormalities are described, including an increased prevalence of
      cysts/pseudocysts of the maxillary sinuses (PCMs) and the presence of maxillary
      prognathism. CONCLUSION: Given the high prevalence of oral and dental
      abnormalities, we recommend a thorough stomatologic evaluation of these patients.

PMID- 11598577
TI  - Severe oral mucositis after therapeutic administration of [131I]MIBG in a child
      with neuroblastoma.
AB  - OBJECTIVE: The purpose of this report is to document a newly encountered oral
      side effect of targeted radiotherapy with iodine 131-metaiodobenzylguanidine
      ([(131)I]MIBG) in the treatment of neuroblastoma. STUDY DESIGN: A 14-month-old
      girl was diagnosed with stage 4 neuroblastoma. After completion of chemotherapy,
      the tumor showed no signs of regression; treatment with 3700 MBq [(131)I]MIBG was
      therefore decided on, 8 months after diagnosis. RESULTS: Fourteen days after
      infusion of MIBG, severe oral mucositis was diagnosed, with a generalized
      erythema involving the mucous membranes of the hard and soft palate, buccal
      mucosa, and upper and lower lips. The gingiva exhibited a general linear
      erythema. CONCLUSIONS: Visualization of the salivary glands on [(123)I]MIBG
      images suggests that accumulation of radiolabeled MIBG in the salivary glands may
      be related to sympathetic innervation.

PMID- 11598579
TI  - Odontogenic keratocyst with mural cartilaginous metaplasia: a case report and a
      review of the literature.
AB  - Odontogenic keratocyst displaying foci of cartilaginous metaplasia in the
      connective tissue wall has been previously reported but is considered rare. We
      report a case of a 66-year-old man with an odontogenic keratocyst of the
      mandible. Benign-appearing metaplastic cartilage was observed in the wall of this
      cyst, as well as in the recurrence. A benign clinical course is documented, and a
      review of the literature detailing 6 previously reported cases is presented.

PMID- 11598578
TI  - The importance of routine magnetic resonance imaging in trigeminal neuralgia
      diagnosis.
AB  - The aim of the study was to determine the frequency of structural lesions
      diagnosed on magnetic resonance imaging (MRI) in a sample of patients with
      trigeminal neuralgia (TN) and to compare history and clinical features between
      the groups with and without structural lesions. Clinical records and MRI findings
      of 42 consecutive patients diagnosed with TN at the National Dental Centre,
      Singapore, and who underwent routine MRI examinations at diagnostic workup
      between April 1997 and March 1999 were retrospectively studied. Of these, 6
      (14.3%; 95% confidence interval, 0 to 28.8%) were diagnosed with an associated
      structural lesion. Mean age of the group with structural lesions was 53.3 years
      (standard deviation, 10.9 years) at presentation, there was female predominance
      (M:F = 1:2), and all (100.0%) gave a typical pain history and had unilateral
      involvement of a single division of the trigeminal nerve. Two patients (33.3%)
      had other cranial nerve abnormalities. Three patients (50.0%) had complete, 2
      patients (33.3%) had partial, and 1 patient (16.7%) had poor response to medical
      therapy. None of these variables was statistically different from the group
      without structural lesions (cranial nerve abnormalities were not compared). In
      conclusion, the frequency of structural lesions associated with TN in our sample
      was relatively high. It is not possible to reliably identify high risk patients
      for selective MRI indication on the basis of history and clinical features. It
      may be prudent to consider routine MRI for all patients with TN to exclude
      structural lesions.

PMID- 11598580
TI  - Intracanal use of a corticosteroid-antibiotic compound for the management of
      posttreatment endodontic pain.
AB  - OBJECTIVE: The purpose of this randomized, double-blind study was to determine
      the effect of a corticosteroid-antibiotic combination when used as an intracanal
      medicament for the treatment of posttreatment pain in endodontically involved
      teeth with vital pulp-test readings. STUDY DESIGN: Out of 988 patients, 480
      experienced intratreatment pain. Endodontic treatment was completed in 3 visits.
      Patients who experienced pain after the first or second visit (postextirpation or
      postinstrumentation) were given an emergency visit during which no local
      anesthetic was used. The patients randomly received either intracanal
      corticosteroid-antibiotic compound or a placebo. Patients subjectively rated
      their pain on a scale of 1 to 4 as none, mild, moderate, and severe. The ratings
      were done at 1, 2, 4, 8, 12, and 24 hours postmedication. RESULTS: Intracanal use
      of the corticosteroid-antibiotic medication significantly reduced (P < .001) the
      mean pain score quite rapidly and was significantly superior to the placebo until
      the end of the study (P < .001). Furthermore, there were no reoccurrences of
      pain, and no side effects from use of the drug were noted. CONCLUSION: These
      results support the intracanal use of corticosteroid-antibiotic combination for
      controlling posttreatment endodontic pain.

PMID- 11598581
TI  - Endodontic infection caused by localized aggressive periodontitis: a case report
      and bacteriologic evaluation.
AB  - A rare case of a periodontally induced endodontic lesion in a systemically
      healthy subject of 28 years is described. The patient, having presented with
      severe attachment loss on the palatal and distal aspects of his maxillary right
      second premolar, was diagnosed with localized aggressive periodontitis. He had
      never received periodontal treatment. The tooth was nonvital and showed all signs
      of symptomatic apical periodontitis. It was also free of any restoration. All
      clinical findings clearly suggested that the endodontic problem was caused by the
      aggressive periodontal disease. Bacteriologic screening of the pocket and the
      root canal, by using "checkerboard" DNA-DNA hybridization analysis, revealed
      diverse flora in the periodontal lesion. The sample obtained from the root canal
      exhibited DNA from a limited number of species, including black-pigmented
      anaerobic rods. No bacterial DNA was found in the root canal that was not also
      recovered from the periodontal pocket.

PMID- 11598582
TI  - The effect of sodium hypochlorite and chlorhexidine on cultured human periodontal
      ligament cells.
AB  - OBJECTIVE: The objective of this study was to examine the effects of sodium
      hypochlorite (NaOCl) and chlorhexidine (CHx) on cultured human periodontal
      ligament (PDL) cells in vitro. STUDY DESIGN: The effects of irrigation solutions
      on human PDL cells were evaluated by propidium iodide fluorescence cytotoxicity
      assay, protein synthesis assay, and mitochondrial activity. RESULTS: Both NaOCl
      and CHx were cytotoxic to human PDL cells in a concentration- and contact time
      dependent manner. In addition, CHx inhibited protein synthesis in human PDL
      cells. Although NaOCl displayed cellular cytotoxicity, it showed no protein
      inhibition in the PDL cells. Furthermore, both NaOCl and CHx exhibited an
      inhibitory effect on mitochondrial activity on human PDL cells. CONCLUSIONS: This
      study suggests that these irrigation fluids may cause detrimental effects on
      vital tissues. Its clinical significance, however, needs to be evaluated further
      because concentration used, exposure time to the agent, and exposure surface area
      are important factors affecting the resulting effect.

PMID- 11598583
TI  - Microbiological evaluation of acute periradicular abscesses by DNA-DNA
      hybridization.
AB  - OBJECTIVE: The purpose of the present investigation was to examine the microbiota
      of acute periradicular abscesses of endodontic origin by using a molecular
      genetic method. STUDY DESIGN: Pus was collected by aspiration from 27 cases
      diagnosed as acute abscesses of endodontic origin, and DNA was extracted to
      evaluate the occurrence of 49 bacterial species by using whole genomic DNA probes
      and checkerboard DNA-DNA hybridization. The presence of bacterial DNA in clinical
      samples was confirmed by polymerase chain reaction with ubiquitous bacterial 16S
      rRNA gene primers. RESULTS: The results of the checkerboard DNA-DNA hybridization
      analysis revealed that 37 of the 49 DNA probes tested were reactive with one or
      more samples. The number of bacterial species in the pus samples ranged from 1 to
      33 (mean, 5.9). Eighteen of the 27 pus samples were positive for at least one DNA
      probe. The most prevalent species found were: Bacteroides forsythus (29.6% of the
      cases); Porphyromonas gingivalis (29.6%); Streptococcus constellatus (25.9%),
      Prevotella intermedia (22.2%), Prevotella nigrescens (22.2%), Fusobacterium
      periodonticum (18.5%), Fusobacterium nucleatum subspecies nucleatum (18.5%), and
      Eikenella corrodens (18.5%). CONCLUSIONS: The microbiologic data of the present
      investigation indicated that molecular genetic methods could provide additional
      knowledge regarding the microbiota of acute periradicular abscesses by detecting
      bacterial species that are difficult--or even impossible--to grow.

PMID- 11598584
TI  - Impact of conventional tomography on prediction of the appropriate implant size.
AB  - AIM: The purpose of this study was to evaluate the efficacy of conventional cross
      sectional tomography in predicting the appropriate implant size. METHODS: The
      implant length and width of 46 patients referred for single tooth implant
      treatment were determined presurgically by periapical + panoramic images (record
      1) and after surgery by periapical + panoramic images + tomograms (record 2).
      These dimensions were compared with the dimensions of the implants actually
      installed (record 3), as well as the dimensions assessed to be the "appropriate"
      ones according to defined criteria for success (record 4). RESULTS: In 70% of the
      cases, the implant length or width, or both, was changed after the tomogram was
      available. The implant dimensions determined with tomography were maintained at
      surgery in 87% of the cases. In only 33% of the cases did the implant size
      predicted without tomography correspond with the size of the installed implants.
      The agreement between records 2 and 3 was significantly higher than between
      records 1 and 3 (P < .001). Similarly, the agreement between records 2 and 4 was
      significantly higher than between records 1 and 4 (P < .001). CONCLUSIONS: This
      study demonstrated that the use of tomograms increases the efficacy of periapical
      + panoramic images, with respect to the prediction of appropriate implant size,
      by a factor of 2.5. Therefore, conventional cross-sectional tomography is
      recommended for treatment planning before installation of single tooth implants.

PMID- 11598585
TI  - The image of the hard palate/nasal fossa floor in panoramic radiography: the
      controversy is over.
AB  - OBJECTIVE: The aim of this investigation was to obtain further information about
      the anatomic structures involved in the formation of the upper image of the hard
      palate/nasal fossa floor (HP/NFF). STUDY DESIGN: Three dry human skulls underwent
      ostectomies along the HP midline (ie, the area of the junction of the nasal
      septum with the nasal fossa floor) and along posterior portions of the HP/NFF
      (ie, the horizontal plates of the palatine bones and part of the palatine
      processes of the maxillae). The radiographs were digitized and preostectomy and
      postostectomy optical densities were measured. Preostectomy and postostectomy
      optical densities were also measured. RESULTS: Partial disappearance of the upper
      image occurred after ostectomy of the junction of the nasal septum with the NFF.
      Total disappearance occurred only after bilateral ostectomy of the posterior
      portions of the HP/NFF. The mean increases in regional optical density in terms
      of pixel gray level after the ostectomies were 70.44%, 72.27%, and 51.40%.
      CONCLUSIONS: The junction of the nasal septum with the NFF and the posterior
      portions of the HP/NFF form the upper image of the HP/NFF. Most of the image is
      real, although a small part is a ghost image of the horizontal plates of the
      palatine bones and of the posterior region of the palatine processes of the
      maxillae.

PMID- 11598586
TI  - The relationship between radiologic interpretation and root tip fracture during
      tooth extraction performed by junior clinicians.
AB  - OBJECTIVES: The purpose of this study was to analyze the relationship between
      root tip fracture and radiologic interpretation of root morphology on periapical
      radiographs during third molar extraction performed by junior clinicians.
      METHODS: Before tooth extraction, periapical radiographs of 107 patients with 116
      third molars were evaluated by junior clinicians, all with less than 5 years of
      clinical experience. Radiologic interpretations of root morphology-including
      number, curvature, fusion, and accessory root-were recorded before each
      extraction. The clinicians were also asked to estimate the possibility of root
      fracture on a Visual Analogue Scale before the procedure. The exact morphology of
      the extracted teeth was recorded after the extraction for the purpose of
      comparison. RESULTS: Twenty-nine of 116 teeth extracted were not correctly
      interpreted in at least 1 of the morphologic categories surveyed. The average
      expected fracture rate of nonfractured teeth was 23.1%, whereas the average
      expected fracture rate of fractured teeth was a significantly higher 50.3%.
      Misinterpretation of root morphology on radiographs decreased with increased
      clinical experience. Senior residents had the lowest misinterpretation and
      fracture rate. Logistic regression analysis showed that fracture is most closely
      related to the estimated fracture rate (4.95) and is also significantly related
      to underestimation of root curvature (0.95; 24.56 with 2 df of chi-square, P =
      .0001). CONCLUSIONS: Misinterpretation of root morphology on radiographs occurred
      in 25% of the teeth. Root curvature was the most misinterpreted item studied.
      Fracture was most closely related to the estimated fracture rate. Junior
      clinicians in this study expected that only 50% of the fractured teeth would
      fracture, reflecting a general underestimation of root tip fracture. Further
      study should be performed to evaluate how to increase the accuracy of root
      curvature interpretation.

PMID- 11598587
TI  - MR imaging and thermography of facial angioedema: a case report.
AB  - Magnetic resonance imaging and thermography were performed in a 67-year-old man
      with idiopathic facial angioedema. Thermography suggested decreased heat emission
      in the region of the angioedema. Magnetic resonance imaging revealed diffuse high
      intensity in the subcutaneous interstitial tissue and dilated veins on T2
      weighted images. Marked contrast enhancement was noted in the subcutaneous tissue
      on postcontrast T1-weighted images.

PMID- 11598588
TI  - The treatment of cystic fibrosis--step by step.

PMID- 11598589
TI  - History matters: why history is of importance to academic pediatricians in the
      21st century.

PMID- 11598590
TI  - The significance of high bone density in children.

PMID- 11598591
TI  - Shedding light on the very low birth weight infant.

PMID- 11598592
TI  - Lung injury in neonates: causes, strategies for prevention, and long-term
      consequences.

PMID- 11598593
TI  - Federation of Pediatric Organizations subspecialty forum.

PMID- 11598594
TI  - Resistance training and bone mineral density in adolescent females.
AB  - OBJECTIVE: To examine the effects of 15 months of resistance training on bone
      mineral density (BMD) in female adolescents (aged 14 to 17 years). STUDY DESIGN:
      Participants were randomly assigned to either a training (n = 46) or control
      group (n = 21). BMD and body composition were measured by using dual-energy x-ray
      absorptiometry. Strength was assessed by means of one-repetition maximums for the
      leg press and bench press. The exercise group trained 30 to 45 minutes a day, 3
      days per week, using 15 different resistance exercises. Control participants
      remained sedentary (<2 hours of exercise per week). RESULTS: Leg strength
      increased significantly (40%) in the exercise group, but there were no changes in
      the control group. Femoral neck BMD increased significantly in the training group
      (1.035 to 1.073 g/cm(2), P <.01) but not in the control group (1.034 to 1.048
      g/cm(2)). No significant changes were seen in either group in lumbar spine BMD
      (1.113 to 1.142 g/cm(2) and 1.158 to 1.190 g/cm(2), respectively) or total body
      BMD (1.103 to 1.134 g/cm(2) and 1.111 to 1.129 g/cm(2), respectively).
      CONCLUSION: Resistance training is a potential method for increasing bone density
      in adolescents, although such a program would be best done as part of the school
      curriculum.

PMID- 11598595
TI  - A school-based exercise intervention augments bone mineral accrual in early
      pubertal girls.
AB  - OBJECTIVE: To evaluate the effects of an elementary school-based physical
      education exercise intervention program on bone mineral accrual in prepubertal
      and early pubertal girls. STUDY DESIGN: A total of 14 schools were randomly
      assigned to control (C) and intervention (I) groups. Girls in the I group
      completed a 10-minute, 3 times per week circuit of varied jumping activities over
      7 months. We measured total body, lumbar spine, proximal femur, femoral neck, and
      trochanteric bone mineral content and areal bone mineral density and estimated
      femoral neck volumetric bone mineral density at baseline and final measurement in
      87 girls in the I group and 90 girls in the C group. Girls were between 8.7 and
      11.7 years at baseline. Tanner stage 1 girls were considered prepubertal; Tanner
      stages 2 and 3 girls were considered early pubertal. We used analysis of
      covariance (adjusting for baseline bone values, change in size, age, and
      maturity) to compare 7-month change in bone mineral content, areal bone mineral
      density, and volumetric bone mineral density between C and I groups within
      prepubertal and early pubertal girls. RESULTS: There was no difference in 7-month
      change in bone parameters between prepubertal I and C groups. Early pubertal
      girls in the I group gained 1.5% to 3.1% more bone at the femoral neck and lumbar
      spine than early pubertal girls in the C group (P <.05); gain at other sites did
      not differ. CONCLUSIONS: In girls, early puberty may be a particularly opportune
      time during growth for simple exercise interventions to have a positive effect on
      bone health.

PMID- 11598596
TI  - Bone mineral density and body composition in boys with distal forearm fractures:
      a dual-energy x-ray absorptiometry study.
AB  - OBJECTIVE: To determine whether boys with distal forearm fractures differ from
      fracture-free control subjects in bone mineral density (BMD) or body composition.
      STUDY DESIGN: A case-control study of 100 patients with fractures (aged 3 to 19
      years) and l00 age-matched fracture-free control subjects was conducted. Weight,
      height, and body mass index were measured anthropometrically. BMD values and body
      composition were determined by dual-energy x-ray absorptiometry. RESULTS: More
      patients than control subjects (36 vs l4) were overweight (body mass index >85th
      percentile for age, P <.001). Patients had lower areal (aBMD) and volumetric
      (BMAD) bone mineral density values and lower bone mineral content but more fat
      and less lean tissue than fracture-free control subjects. The ratios (95% CIs)
      for all case patients/control subjects in age and weight-adjusted data were
      ultradistal radius aBMD 0.94 (0.91-0.97); 33% radius aBMD 0.96 (0.93-0.98) and
      BMAD 0.95 (0.91-0.99); spinal L2-4 BMD 0.92 (0.89-0.95) and BMAD 0.92 (0.89
      0.94); femoral neck aBMD 0.95 (0.92-0.98) and BMAD 0.95 (0.91-0.98); total body
      aBMD 0.97 (0.96-0.99), fat mass 1.14 (1.04-1.24), lean mass 0.96 (0.93-0.99), and
      total body bone mineral content 0.94 (0.91-0.97). CONCLUSIONS: Our results
      support the view that low BMC, aBMD, and BMAD values and high adiposity are
      associated with increased risk of distal forearm fracture in boys. This is a
      concern, given the increasing levels of obesity in children today.

PMID- 11598597
TI  - A prospective, longitudinal study of the long-term effect of treatment on bone
      density in children with celiac disease.
AB  - OBJECTIVE: Because osteopenia is a frequent complication of celiac disease, we
      evaluated the impact of a long-term gluten-free diet (GFD), initiated during
      childhood, on bone density. study design: Patients with celiac disease (n = 19;
      mean age, 14.2 +/- 2.6 years) were studied after 4.3 +/- 0.6 years of GFD. Bone
      density had been measured at diagnosis and after 1 year of GFD. We also studied
      211 healthy children as a control group. Bone mineral density was measured by
      dual-energy x-ray absorptiometry. Intact parathyroid hormone (PTH) and bone
      specific alkaline phosphatase (BALP) levels were measured in serum, and N
      terminal telopeptide of type I collagen (NTx) was measured in urine. RESULTS:
      Although at diagnosis bone mineral content, bone area, and bone mineral density
      were significantly lower than in control subjects, the 3 measurements were normal
      after GFD. None of the patients on a GFD showed elevated values of PTH. Patients
      on a GFD had BALP (110.2 +/- 67.2 U/L) and NTx levels (261.9 +/- 187.8 nmol bone
      collagen equivalents/mmol creatinine) that were significantly higher than those
      of control subjects. The levels of BALP and NTx were significantly higher in
      patients with good compliance with the GFD, compared with patients with poorer
      compliance. CONCLUSIONS: This study shows that bone mineral content, bone area,
      and bone mineral density improve significantly with a GFD.

PMID- 11598598
TI  - Calcium fortification of breakfast cereal enhances calcium absorption in children
      without affecting iron absorption.
AB  - OBJECTIVES: Provision of calcium-fortified foods may represent an important
      component of improving the calcium intake of children. We sought to determine
      whether the addition of calcium to cereal would have a net positive effect on
      calcium absorption without decreasing iron absorption. METHODS: Twenty-seven
      children, 6 to 9 years of age, were provided two servings per day (30 g of cereal
      per serving) of either a low (39 mg/serving) or fortified (156 mg/serving)
      calcium-containing cereal product for 14 days. Calcium absorption was measured by
      using stable isotopes added to milk (extrinsically labeled) and to the calcium
      fortified cereal (intrinsically labeled). RESULTS: Fractional calcium absorption
      from the fortified cereal was virtually identical to that from milk. Fractional
      absorption of calcium from milk did not differ significantly when given with
      enriched or low-calcium-containing cereal. Total calcium absorption increased
      from 215 +/- 45 mg/d to 269 +/- 45 mg/d with the addition of the calcium
      fortified cereal (P <.001). Iron absorption was similar when children received
      the calcium-fortified cereal or unfortified cereal. CONCLUSIONS: The addition of
      a moderate amount of calcium to a cereal product was beneficial to calcium
      absorption and did not interfere with iron absorption. Use of calcium-fortified
      food products may be considered a practical approach to increasing the calcium
      intake of children.

PMID- 11598599
TI  - Reduced lighting does not improve medical outcomes in very low birth weight
      infants.
AB  - OBJECTIVE: To objectively assess the effect of light reduction as an isolated
      environmental intervention on neonatal morbidity. STUDY DESIGN: Randomized
      multicenter trial. Neonates < 1251 g birth weight and < 31 weeks gestational age
      were randomly assigned to receive goggles or to a control group. Goggles that
      reduced visible light by 97% were placed within 24 hours of birth and remained in
      use until 31 weeks postmenstrual age or for a minimum of 4 weeks. RESULTS: Four
      hundred nine infants were enrolled, and outcome data are reported for 359
      surviving infants. There were no significant differences between the groups in
      weight gain, duration of oxygen therapy, mechanical ventilation, or hospital stay
      either in the unadjusted analyses or in the analyses adjusted for birth weight,
      gestational age, race, sex, and inborn (born in study hospital) status. There was
      no difference between the groups in the incidence of intracranial hemorrhage.
      CONCLUSIONS: This randomized trial of continuous light reduction in the first few
      weeks of life for very low birth weight infants showed no effect on medical
      outcomes.

PMID- 11598600
TI  - Are human milk long-chain polyunsaturated fatty acids related to visual and
      neural development in breast-fed term infants?
AB  - OBJECTIVE: To determine whether docosahexaenoic acid (DHA) is related to visual
      and neural development in term breast-fed infants. DESIGN: A prospective study of
      83 infants who were exclusively breast-fed for at least 3 months. We determined
      red blood cell and plasma fatty acids at 2 months, visual acuity at 2, 4, 6, and
      12 months, speech perception and an object search task at 9 months, Bayley's
      mental development index and psychomotor development index at 6 and 12 months,
      and novelty pReference at 6 and 9 months. RESULTS: The infant red blood cell
      phosphatidylethanolamine DHA was significantly related to visual acuity at 2
      months of age (r = 0.32, P =.01) and 12 months of age (r = 0.30, P =.03). The
      ability to discriminate nonnative retroflex and phonetic contrasts at 9 months of
      age was related to the plasma phospholipid DHA (r = 0.48, P <.02) and red blood
      cell phosphatidylethanolamine DHA (r = 0.26, P =.02) at 2 months of age after
      adjusting for covariates. CONCLUSION: DHA may influence the development of visual
      acuity and neural pathways associated with the developmental progression of
      language acquisition in term breast-fed infants. The extent to which our results
      can be attributed solely to DHA from maternal sources through breast milk or in
      gestation or other confounding factors remains to be determined.

PMID- 11598601
TI  - Development of left ventricular systolic and diastolic function in preterm
      infants during the first month of life: a prospective follow-up study.
AB  - OBJECTIVES: We studied the left ventricular systolic and diastolic function in
      preterm infants during the first month of life in comparison with the respective
      patterns in term neonates. STUDY DESIGN: Serial 2-dimensional/M-mode and Doppler
      transmitral flow velocity measurements were performed in 20 preterm (gestational
      age, 32 to 36 weeks) and 25 term infants between days 2 and 5 after birth and at
      age 1 month. RESULTS: After birth, the early velocity, early integral, early
      filling fraction, early and atrial velocity ratios, and early and atrial integral
      ratios were lower in the preterm than in the term infants (P <.01). During the
      first 4 weeks of life, these values, the atrial velocity, and the atrial integral
      increased gradually, whereas the atrial filling fraction, diastolic filling time,
      and deceleration time of early diastolic filling decreased slightly with
      postnatal age (P <.01) in the preterm infants. At age 1 month their diastolic
      function reached the level of term infants with the exception of early and atrial
      integral ratios and atrial filling fraction. The measures of systolic performance
      were within normal range, but midwall fractional shortening at 2 to 5 days (P
      <.05), and fractional shortening area (P <.05), as well as midwall fractional
      shortening (P <.01) at 1 month of age, were slightly inferior in the preterm than
      in the term infants. During the first month the left ventricular mass and left
      ventricular mass/body surface area ratio increased more markedly in the preterm
      than term infants, significantly in both groups (P <.05). CONCLUSIONS: The
      preterm diastolic patterns represent a transition between the patterns of the
      fetus and those of term neonates. These changes reflect an improvement in the
      left ventricular diastolic function, more markedly in relaxation than in
      compliance. The postnatal increase in the transmitral measures and left
      ventricular mass suggest marked myocardial adaptation to the extrauterine
      environment in the preterm infant already during the first month.

PMID- 11598602
TI  - Validity of the Test of Infant Motor Performance for discriminating among infants
      with varying risk for poor motor outcome.
AB  - OBJECTIVE: The objective was to assess the ability of the Test of Infant Motor
      Performance (TIMP) to discriminate among infants with varying degrees of risk for
      motor developmental morbidity on the basis of perinatal medical complications.
      STUDY DESIGN: Ninety-eight infants were tested weekly with the TIMP until 4
      months of age. Comparisons were made among 5 groups of infants: (1) term infants
      without significant medical problems (low risk); (2) infants born prematurely
      with no significant medical problems (medium risk); (3) infants born at <30
      weeks' gestational age or with birth weight <1500 g (high risk); (4) infants with
      chronic lung disease (high risk); and (5) infants with brain insults (high risk).
      A random-effects growth curve analysis assessed differences between the groups in
      slope and level of development across time. RESULTS: Infants in the low- and
      medium-risk groups did not differ from each other but were significantly better
      performers than infants in the high-risk groups. Infants with brain insults
      performed significantly less well than all other infants, both in absolute level
      of performance and in developmental slope across time. Performance by black
      infants averaged 2 points higher than that of other infants. CONCLUSIONS: The
      TIMP can discriminate among infants with differing risks for motor developmental
      delay.

PMID- 11598603
TI  - Long-term neurobehavioral outcomes in children with neuroblastoma and opsoclonus
      myoclonus-ataxia syndrome: relationship to MRI findings and anti-neuronal
      antibodies.
AB  - OBJECTIVES: Opsoclonus-myoclonus-ataxia (OMA) syndrome affects 2% to 3% of
      patients with neuroblastoma. This study examined relationships between long-term
      neurobehavioral outcomes and potential biologic markers of OMA, including chronic
      changes on magnetic resonance imaging (MRI) brain scanning and prevalence of late
      antineuronal antibodies. STUDY DESIGN: Children with neuroblastoma and OMA were
      identified through medical record review of patients treated at the University of
      California at San Francisco Medical Center from 1979 to 1999. Eleven patients
      with a mean follow-up time of 7.6 years underwent standard neurologic,
      neurocognitive, developmental/behavioral, and academic assessments. Consenting
      patients underwent MRI brain scanning and a blood draw. Sera were analyzed for
      the presence of antineuronal immunoreactivity. RESULTS: Two (18%) patients had no
      observed neurologic abnormalities, 7 (64%) demonstrated mild deficits, and 2
      (18%) had severe neurologic deficits. However, on neurocognitive, behavioral, and
      academic assessments, 6 (55%) children performed within the average range, 1 (9%)
      was moderately below average and 4 (36%) had severe cognitive and behavioral
      deficiencies. Brain MRI in 5 of 5 patients was notable for cerebellar atrophy
      without supratentorial involvement. Antineuronal activity was detected in sera of
      0 of 10 children at follow-up. CONCLUSIONS: Certain patients with neuroblastoma
      associated OMA may achieve average-range neurobehavioral function in spite of
      residual neurologic abnormalities, with suggestion of continued improvement over
      time. Late cerebellar atrophy appears to be a common finding regardless of
      neurologic outcome, whereas antineuronal immune reactivity does not appear to be
      a long-term feature of OMA.

PMID- 11598604
TI  - Growth hormone treatment in children with chronic renal failure: a meta-analysis
      of randomized controlled trials.
AB  - OBJECTIVE: To evaluate the benefits and side effects of recombinant human growth
      hormone (hGH) treatment in children with chronic renal failure. METHODS: Two
      reviewers independently assessed relevant randomized controlled trials for
      methodologic quality, extracted data, and estimated summary treatment effects by
      use of a random effects model. RESULTS: Ten randomized controlled trials
      involving 481 children were identified. Treatment with hGH (28 IU/m(2)/wk)
      resulted in a significant increase in height standard deviation score at 1 year
      (4 trials, weighted mean difference [WMD] = 0.77, 95% CI = 0.51 to 1.04), and a
      significant increase in height velocity at 6 months (2 trials, WMD = 5.7 cm/y,
      95% CI 4.4 to 7.0) and 1 year (2 trials, WMD = 4.1 cm/y, 95% CI 2.6 to 5.6), but
      there was no further increase in height indexes during the second year of
      administration. Compared with the 14 IU/m(2)/wk group, there was an increase of
      1.4 cm/y (0.6 to 2.2) in height velocity in the group treated with 28 IU/m(2)/wk.
      The frequency of reported side effects of hGH were similar to that of the control
      group. CONCLUSION: On average, 1 year of treatment with 28 IU/m(2)/wk hGH in
      children with chronic renal failure results in an increase of 4 cm/y in height
      velocity above that of untreated control subjects, but there was no demonstrable
      benefit for longer courses or higher doses of treatment.

PMID- 11598605
TI  - Timing of voiding cystourethrogram in the investigation of urinary tract
      infections in children.
AB  - OBJECTIVE: To determine whether the detection of vesicoureteral reflux (VUR) in
      children with a urinary tract infection (UTI) is more likely if the voiding
      cystourethrogram (VCUG) is performed early (within the first 7 days after
      diagnosis) or late (>7 days after diagnosis). STUDY DESIGN: We conducted a
      retrospective case review of children <5 years of age admitted with a first
      episode of UTI to a tertiary care pediatric hospital over a 2-year period. Timing
      of the VCUG was at the discretion of the attending pediatrician. Differences in
      age, sex, mean time to performing the VCUG, and incidence of VUR between the 2
      groups (VCUG performed early vs late) were compared by using Student t test (for
      age) and chi(2) test (for sex and incidence of VUR). Potential confounders (age
      and sex) were included in a multiple logistic regression analysis. RESULTS: A
      total of 162 patients were eligible for inclusion. Mean age was 181 days, and
      43.8% were female. The incidence of VUR was 21.6%. The early group consisted of
      82 patients, and the late group consisted of 80. No significant difference was
      found for age or sex or for the incidence of reflux (17.1% vs 26.3%, P =.219),
      with a crude odds ratio of.59 (95% CI 0.3-1.2, P >.05). CONCLUSION: The rate of
      detection of VUR in children with a first episode of UTI does not increase when
      the VCUG is done early (within the first 7 days of diagnosis) rather than later.

PMID- 11598607
TI  - Randomized clinical trial of soy formula with and without added fiber in
      antibiotic-induced diarrhea.
AB  - OBJECTIVE: The objective of this study was to examine the effects of soy formulas
      with and without added soy fiber in children who developed diarrhea while
      receiving antibiotics. DESIGN: In a masked, randomized parallel study, older
      infants and toddlers were fed commercial soy formulas with or without added soy
      fiber for 10 days on occurrence of diarrhea during the administration of
      antibiotics. Subjects were stratified by feeding (formula versus cow's milk). The
      primary variables were duration of diarrhea, stool characteristics, and intake.
      Secondary variables were weight and spit-up. RESULTS: All 45 children who
      completed the 10-day study received >30% of their caloric intake from formula.
      Fiber intake from other foods did not differ between groups and averaged 0.5
      g/day. Total median fiber intake of the group fed the formula with added fiber
      was 6.53 g/day. The mean duration of diarrhea was 25.1 +/- 5.2 hours for children
      fed the formula with added fiber and 51.6 +/- 10.7 hours for those fed the
      regular formula (P =.0013). CONCLUSION: The duration of antibiotic-induced
      diarrhea in children fed the soy formula with added soy fiber was significantly
      reduced.

PMID- 11598608
TI  - Restricted diets in children with reactions to milk and egg perceived by their
      parents.
AB  - The aim of this study was to investigate the degree to which parents alter the
      diets of their children on the basis of perceived reactions. From a population
      based sample of 2979 2-year old children with reactions to egg or milk perceived
      by their parents, one third had strict limitations on the intakes of these foods,
      representing 2.5% of the children in the cohort. In approximately 1 of 6 families
      the strict diets were initiated without consulting a doctor, and in a substantial
      proportion the restrictions were unwarranted. High maternal education level and
      irritability attributed to food were among the risk factors for unwarranted
      diets. On the other hand, many children, in whom an adverse reaction was
      verified, lacked appropriate diet restrictions. We conclude that the handling of
      adverse reactions to food frequently occurs outside the medical care system at
      the cost of correct diagnosis and appropriate diets.

PMID- 11598606
TI  - Serum and lower respiratory tract drug concentrations after tobramycin inhalation
      in young children with cystic fibrosis.
AB  - OBJECTIVES: To assess the serum and lower respiratory tract tobramycin
      concentrations (C(T)) produced by a single dose of tobramycin for inhalation
      delivered by a nebulizer and a compressor in patients with cystic fibrosis (CF) 6
      months to 6 years of age. STUDY DESIGN: We performed a dose escalation study of
      serum C(T) measured before and 0.5, 1, 2, and 4 hours after a single dose of
      inhaled tobramycin, either 180 mg (10 patients) or 300 mg (19 patients). In a
      separate group of 12 patients, epithelial lining fluid (ELF) C(T) was measured by
      bronchoalveolar lavage 30 to 45 minutes after a 300-mg dose. RESULTS: A 180-mg
      dose of inhaled tobramycin produced a mean peak serum C(T) of 0.5 microg/mL (SD
      0.4; range, <0.2 to 1.4 microg/mL). A 300-mg dose produced a mean peak serum C(T)
      of 0.6 microg/mL (SD 0.5; range, <0.2 to 1.2 microg/mL). These peak values are
      well below the accepted maximum trough concentration with parenteral dosing (2
      microg/mL). The target ELF C(T) was 20 microg/mL, 10-fold greater than the
      minimal inhibitory concentration for most Pseudomonas aeruginosa isolates from
      very young patients with CF (2 microg/mL). Mean ELF C(T) was 90 microg/mL (SD 54;
      range, 16 to 204 microg/mL) and exceeded the target concentration in 11 patients.
      CONCLUSION: In patients with CF ages 6 months to 6 years, a single 300-mg dose of
      inhaled tobramycin appears to produce safe peak serum concentrations and drug
      concentrations in the bactericidal range in the lower respiratory tract.

PMID- 11598609
TI  - Pierre Robin sequence: a series of 117 consecutive cases.
AB  - A series of 117 cases of Pierre Robin Sequence are classified as isolated (48%),
      syndromic (35%), and with associated anomalies (17%); the latter group had a poor
      long-term prognosis. In isolated Pierre Robin Sequence, familial cases and a high
      incidence of twins were noted. Among syndromic Pierre Robin Sequence, 4 syndromes
      represent more than 50% of the diagnoses.

PMID- 11598610
TI  - Double catheter technique for misdirected umbilical vein catheter.
AB  - We studied the success rate of the double catheter technique during umbilical
      vein catheter placement in 42 patients with a misdirected umbilical vein
      catheter. The misdirected catheter was left in place, and an additional catheter
      was inserted. X-ray films confirmed that successful placement was achieved in 50%
      of infants without significant adverse effects.

PMID- 11598611
TI  - Recombinant tissue plasminogen activator in the treatment of central venous
      catheter occlusion in children.
AB  - Tissue plasminogen activator was used to treat 228 children with 320 central
      venous catheter (CVC) occlusion events. Patency was restored in 91% of CVCs after
      1 to 3 treatments, with no adverse events. Tissue plasminogen activator is
      effective in restoring patency to occluded CVCs and is a viable alternative to
      CVC removal or urokinase treatment.

PMID- 11598612
TI  - Thyroid dysgenesis caused by PAX8 mutation: the hypermutability with CpG
      dinucleotides at codon 31.
AB  - We identified a novel mutation (CGC to T GC) at codon 31 of the Paired box 8
      gene, an important transcription factor in the development of the thyroid gland.
      Mutations at this codon have been independently reported in 2 cases (CGC to CA
      C). These transitions are considered typical CpG-consequence mutations and
      account for hypermutability at this position.

PMID- 11598614
TI  - The treatment of acute respiratory failure in children: a historical examination
      of landmark advances.

PMID- 11598613
TI  - Interferon-gamma receptor deficiency mimicking Langerhans' cell histiocytosis.
AB  - Two patients who were initially given a diagnosis of Langerhans' cell
      histiocytosis on the basis of the clinical, radiologic, and biopsy findings had
      mycobacterial infection subsequently identified. The correct diagnosis of
      dominant partial interferon-gamma receptor deficiency was established.

PMID- 11598615
TI  - Daytime wetting.

PMID- 11598618
TI  - Suicide gene therapy for bladder tumors.

PMID- 11598617
TI  - Another issue in traditional medical therapy for congenital adrenal hyperplasia.

PMID- 11598619
TI  - Ebola hemorrhagic fever (EHF): mechanism of transmission and pathogenicity.
AB  - Hemorrhagic fevers represent a wide spectrum of viral infectious diseases, out
      breaking mostly as epidemics, some of them being highly lethal. They range from
      those caused by bunyaviridae, associated with renal or pulmonary syndromes and
      those recently emerging and caused by the filoviridae family of thread-like
      viruses. Among the latter, Ebola hemorrhagic fever (EHF) bears the highest
      mortality and morbidity rates. One form of the disease has been documented only
      in monkeys. The human form, has occurred mainly in areas surrounding rain forests
      in central Africa. Patients present with signs of hemorrhagic diathesis, fever,
      diarrhea and neurological disorders, leading sometimes to confusion with local
      endemic diseases. Fatal victims of the disease die of dehydration. Poor hygienic
      conditions facilitate the spread of the virus. Biologically, the virus seems to
      target both the host blood coagulative and immune defense systems. Intensive
      epidemiologic search have failed to establish the definitive natural host of the
      virus. Twice, with a 19-year interval, major outbreaks have taken place in the
      Democratic Republic of the Congo. The second major outbreak in the northwestern
      city of Kikwit in April 1995 will serve here to elucidate the mechanism of the
      viral infection.

PMID- 11598620
TI  - Muscle sympathetic nerve activity in patients with lumbar spinal canal stenosis.
AB  - The present study aimed to measure sensory nerve conduction velocity (SNCV) and
      muscle sympathetic nerve activity (MSA) in both normal subjects and patients with
      lumbar spinal canal stenosis (LSCS), and to determine what sensory and
      sympathetic nerve systems relate to the development of abnormal sensation in the
      lower limbs of the patients. The study population was 12 patients and 10 age
      matched healthy control subjects. A statistical difference in the mean MSA
      intervals was found between the LSCS patients and the normal subjects. There was
      a fairly large difference between them in the values of the standard deviations
      as one of the parameters to determine the degree of fluctuation of MSA. These
      results suggest the LSCS patients have shorter MSA intervals and narrower
      fluctuations of MSA than normal subjects. As for the range of fluctuation of the
      MSA intervals and SNCV, the faster the SNCV, the wider the range of fluctuation
      of MSA intervals in the normal subjects. Many patients with LSCS seem to maintain
      a correlation between SNCV and MSA intervals. This suggests that even in cases of
      LSCS, human homeostasis works to keep the relationship between sympathetic nerve
      function and somato sensory nerve function to some extent. A few LSCS patients
      showed no correlation between MSA and SNCV. These patients were rather old,
      suffered spinal stenosis in the relatively higher levels of the spinal canal, and
      had suffered from the disease for longer than the mean period of all the
      patients. When the peripheral nerves or cauda epuina are chronically compressed,
      the nerve systems can not maintain the relationship between them, which finally
      results in failure. It is suggested that the disrupted coordination between
      sympathetic nerve function and somato sensory nerve function is one of the
      reasons why abnormal sensations occur in the lower extremities of LSCS patients.

PMID- 11598621
TI  - Expression and localization of basic fibroblast growth factor and its mRNA in
      solitary fibrous tumor.
AB  - Solitary fibrous tumors (SFTs) represent a distinct neoplasm that should be
      included in the differential diagnosis of spindle-cell neoplasms of the soft
      tissue. Basic fibroblast growth factor (bFGF or FGF-2) is a mitogenic and
      angiogenic polypeptide produced by diverse cell types, including the cells
      derived from normal tissue and neoplastic lesions. In this study, the expression
      of bFGF, vimentin, CD 34, c-kit (or CD 117), desmin, S-100 protein, and alpha
      smooth muscle actin (alpha-SMA) in SFTs, hemangiopericytomas (HPC),
      gastrointestinal stromal tumors (GIST), and dermatofibrosarcoma protuberans
      (DFSP) were evaluated to assess their usefulness in the differential diagnosis of
      these lesions. The expression of bFGF mRNA was also examined in SFTs by in situ
      hybridization (ISH) using a digoxigenin-labeled bFGF oligonucleotide probe. All
      the SFTs, GISTs and DFSPs exhibited strong and diffuse immunoreactivity for CD34
      and vimentin, and were completely negative for desmin, S-100 protein and alpha
      SMA. The HPCs were positive for vimentin, but negative for CD34. In all the SFTs,
      strong and diffuse nuclear immunostaining was observed with bFGF antibody,
      contrasting with the negative staining observed in the majority of the HPCs,
      GISTs, and DFSPs. The bFGF mRNA was also expressed in the SFT cells. The
      constitutive expression of the bFGF in the SFT widens the spectrum of available
      markers for these tumors, providing a useful addition to their differential
      diagnosis in difficult cases, and contributing to the understanding of their
      histogenesis and molecular pathogenesis.

PMID- 11598622
TI  - Wide-spread distribution of sentinel lymph nodes in esophageal cancer.
AB  - Sentinel lymph nodes are the first draining nodes that contain tumor cells.
      Identification of sentinel nodes may help to determine the suitable extent of
      lymphadenectoy. To assess the location of sentinel lymph nodes, a series of 41
      patients with single and two metastatic lymph nodes who underwent esophagectomy
      and 3-field lymphadenectomy between 1991 and 1999 were investigated
      retrospectively. Only 29 (47.5%) of 61 metastatic nodes showed correspondence
      between the tumor site and the regional metastatic lymph nodes by routine
      histologic examination. In the patients with tumors in the upper and middle
      thoracic esophagus, metastatic lymph nodes were distributed in the cervix,
      mediastinum and abdomen. Although sentinel nodes were limited to the regional and
      adjusting compartments in 82%, nodes were found beyond the adjusting compartments
      in 18%. The sentinel nodes were broadly distributed depending on the location of
      the tumor in esophageal cancer.

PMID- 11598623
TI  - Expression of fibroblast growth factor (FGF)-10 in human colorectal
      adenocarcinoma cells.
AB  - Fibroblast growth factor (FGF) -10 (keratinocyte growth factor 2, KGF 2) is a new
      member of the FGF family that is mainly synthesized by mesenchymal cells and acts
      predominantly on epithelial cells in a paracrine manner. Its actions are
      dependent on its binding to the iiib isoform of the cell-surface FGF receptor 2
      (FGFR2 iiib). FGF-10 is known to play an important role in fetal limb and lung
      development, skin wound healing and prostatic epithelial cell growth. In the
      present study, the expression of FGF-10 and FGFR2 iiib in five cultured human
      colorectal adenocarcinoma cell lines (COLO 205, DLD-1, HCT-15, SW 480 and WiDr)
      and the localization of FGF-10 messenger RNA (mRNA) and its protein in human
      colorectal cancer tissues from 10 patients were determined. All five colorectal
      cancer cell lines expressed FGF-10 mRNA and its protein. FGFR2 iiib mRNAs were
      expressed in these cells and the recombinant FGF-10 (1 ng/ml) increased the
      growth rate of COLO 205 cells. To determine the localization of FGF-10 protein
      and its mRNA in normal and cancerous human colorectal tissues,
      immunohistochemistry and in situ hybridization were performed. In normal
      colorectal tissues, FGF-10 and its mRNA were not detected. In contrast, moderate
      immunoreactivity was present in cancer cells in 5 of 10 colorectal cancer cases
      and mild immunoreactivity was recognized in adjacent fibroblasts. By using in
      situ hybridization, FGF-10 mRNA was observed in colorectal cancer cells and
      fibroblasts adjacent to cancer cells. These findings indicate that FGF-10 and its
      receptor, FGFR2 iiib expression in colorectal adenocarcinoma cells and FGF-10 may
      contribute to the growth of cells of this type.

PMID- 11598624
TI  - Asymptomatic pyuria in diabetic women.
AB  - The aim of the present study was to determine the prevalence of and the host
      factors for asymptomatic pyuria (ASP) in women with type 2 diabetes. The study
      included 179 type 2 diabetic women and consecutive 455 non-diabetic women
      attending as out-patients in 1996. Patients with symptoms of a urinary tract
      infection were excluded. ASP was defined as the presence of more than 10
      leukocytes/high-power field in a random urine sample. Diabetic women more often
      had ASP than non-diabetic women (27.9 vs. 15.8%, P<0.001). The prevalence of ASP
      was significantly increased in patients with a duration of diabetes exceeding 15
      years (0 approximately 4 years; 20.3%, 5 approximately 9 years; 24.3%, 10
      approximately 14 years; 23.8%, and > or =15 years; 46.3%). No differences were
      evident in HbA(1C) between diabetic patients without ASP and those with ASP.
      Diabetic women with ASP more often had diabetic retinopathy, neuropathy,
      nephropathy, cerebrovascular disease, ischemic heart disease, and hyperlipidemia
      than those without ASP. However, no statistically significant differences were
      evident in the prevalence of hypertension, constipation, or dementia. As the
      degree of neuropathy increases, it is accompanied by an increasing prevalence of
      ASP (none, 21.4%; blunt tendon reflexes, 24.5%; symptomatic, 50.0%; and gangrene,
      66.6%). The prevalence of ASP was significantly increased in the patients with
      proliferative diabetic retinopathy (none, 23.2%; background, 29.4%; pre
      proliferative, 18.2%; and proliferative, 50.0%). As the degree of nephropathy
      increases, it is accompanied by an increasing prevalence of ASP (none, 20.0%;
      microalbuminuria, 31.9%; macroalbuminuria, 37.0%; and renal failure, 60.0%).
      Thus, the prevalence of ASP is increased in women with diabetes and increased
      with longer duration of diabetes but was not affected by glucose control. The
      incidence of ASP increases significantly as diabetic microangiopathy becomes
      severer.

PMID- 11598625
TI  - [cDNA microarray and SNP analysis].

PMID- 11598626
TI  - [Gene expression analysis of human cancer in digestive tract].

PMID- 11598627
TI  - [Molecular diagnosis of breast cancer].

PMID- 11598628
TI  - [Application of SNPs onto the genetic analysis of subarachnoid hemorrhage].

PMID- 11598629
TI  - [Genome-wide SNP scanning for identification of susceptibility genes of
      osteoporosis].

PMID- 11598630
TI  - [Ethical problems in gene medicine].

PMID- 11598631
TI  - Gastrointestinal stromal tumor of the stomach diagnosed preoperatively.
AB  - A case of gastrointestinal stromal tumor (GIST) of the stomach is reported. GIST
      has been applied to gastrointestinal submucosal tumors mainly composed of spindle
      shaped cells that represent neither typical features of myogenic nor neurogenic
      tumors, and immunohistochemical studies are necessary for the diagnosis of GIST.
      The patient was a 39-year-old man and was successfully diagnosed to be GIST
      (uncommitted type) preoperatively by immunohistochemical studies of biopsy
      specimens from an ulcerative submucosal tumor with bridging folds in the fundus,
      approximately 3.0 cm in size. Local excision of the stomach was performed. This
      is the 3rd case of GIST with a preoperative diagnosis to appear in the literature
      in Japan. For gastroenterological surgeons, it is critical to select the most
      suitable surgical procedure. In the present, because the number of papers
      reporting GIST of the stomach is small, it is impossible to review GIST
      clinicopathologically. We reviewed the surgical procedure for gastric
      leiomyosarcomas, because of including many cases with GIST in them. Therefore, we
      performed 54 cases of gastric GIST in the literature, compared with 92 cases of
      gastric leiomyosarcoma. As a result, it was thought that local excision for
      gastric GIST should be preferred.

PMID- 11598632
TI  - A case of infantile cortical hyperostosis.
AB  - Infantile cortical hyperosteosis (ICH) is usually a self-limited disease of
      infancy with bony changes, soft tissue swelling, fever, irritability, decreased
      appetite, and decreased movement of the affected bones. Its description in
      isolated patients or in multiple members of families suggests the existence of
      two different forms, namely a sporadic form and a familial form with incomplete
      penetrance. In this article, we report a 2.5-month-old girl with ICH of sporadic
      form, due to unusual presentation.

PMID- 11598633
TI  - Celiac artery aneurysm: a case evaluated preoperatively with three-dimensional
      computed tomographic angiography.
AB  - In a 63-year-old woman computed tomography (CT) incidentally detected a celiac
      artery aneurysm approximately 3 cm in diameter. While conventional angiography
      suggested that the splenic artery and common hepatic artery arose from the celiac
      artery aneurysm, three-dimensional CT angiography indicated that the aneurysm
      involved only the mid portion of the celiac artery. Considering the risk of
      eventual aneurysm rupture, surgery was performed. Aneurysmectomy and
      devascularization of hepatic, splenic, and celiac arteries were carried out
      following complete cross-clamping of the celiac artery. The distal segment of the
      celiac artery was directly anastomosed to the proximal segment in an end-to-end
      fashion. Histologically, the aneurysm wall showed atheromatous changes. Contrast
      enhanced abdominal CT confirmed complete removal of the celiac artery aneurysm,
      and postoperative angiography confirmed good arterial flow. The patient recovered
      uneventfully after surgery, with normalization of transiently abnormal hepatic
      function parameters. In this case of celiac artery aneurysm, three-dimensional CT
      angiography was found to be valuable in determining the relationships of the
      aneurysms to important arterial branches.

PMID- 11598634
TI  - [Primary aldosteronism].

PMID- 11598635
TI  - Studies of the erythrocyte spectrin tetramerization region.
AB  - Human erythrocyte spectrin dimers associate at the N-terminal region of alpha
      spectrin (alpha N) and the C-terminal region of beta-spectrin (beta C) to form
      tetramers. We have prepared model peptides to study the tetramerization region.
      Based on phasing information obtained from enzyme digests, we prepared spectrin
      fragments consisting of the first 156 amino-acid residues and the first 368 amino
      acid residues of alpha-spectrin (Sp alpha 1-156 and Sp alpha 1-368,
      respectively), and found that both peptides associate with a beta-spectrin model
      peptide, with an affinity similar to that found in alpha beta dimer
      tetramerization. Spin label EPR studies show that the region consisting of
      residues 21-46 in alpha-spectrin is helical even in the absence of its beta
      partner. Multi-dimensional nuclear magnetic resonance studies of samples with and
      without a spin label attached to residue 154 show that Sp alpha 1-156 consists of
      four helices, with the first helix unassociated with the remaining three helices,
      which bundle to form a triple helical coiled coil bundle. A comparison of the
      structures of erythrocyte spectrin with other published structures of Drosophila
      and chicken brain spectrin is discussed. Circular dichroism studies show that the
      lone helix in Sp alpha-156 associates with helices in the beta peptide to form a
      coiled coil bundle. Based on NMR and CD results, we suggest that the helices in
      Sp alpha 1-156 exhibit a looser (frayed) conformation, and that the helices
      convert to a tighter conformation upon association with its beta-partner. This
      suggestion does not rule out possible conversion of a non-structured conformation
      to a structured conformation in various parts of the molecule upon association.
      Spectrin mutations at residues 28 and 45 of alpha-spectrin have been found in
      patients with hereditary elliptocytosis. NMR studies were also carried out on Sp
      alpha 1-156R28S, Sp alpha 1-156R45S and Sp alpha 1-156R45T. A comparison of the
      structures of Sp alpha 1-156 and Sp alpha 1-156R28S, Sp alpha 1-156R45S and Sp
      alpha 1-156R45T is discussed.

PMID- 11598636
TI  - Regeneration of Cuphea tolucana Peyr. in in vitro culture.
AB  - In order to regenerate Cuphea tolucana from hypocotyl, cotyledon and root
      explants, a solid culture and 8 hormone combinations were used. Only the root
      explants did not react to any of the media. On most of the media, the other
      explants formed shoots, roots or callus, or their reaction was more complex. The
      regeneration probably occurred via direct organogenesis. The regenerants
      displayed a wide variety of morphological characteristics. However, their
      offspring did not show any differences from plants, which had not undergone
      culture.

PMID- 11598637
TI  - New insights into red cell network structure, elasticity, and spectrin unfolding-
      a current review.
AB  - The red cell membrane's well-recognized ability to withstand the stresses of
      circulation clearly has its origins in various levels of spectrin-actin network
      structure. We highlight recently obtained insights into this sub-structure and
      also briefly explain the implications to membrane components that interact with
      the network. Novel insights into the resilience of this cytoskeleton are being
      provided by experiments that range from atomic force microscopy (AFM) tests of
      single, unfoldable spectrin chains to micropatterned photobleaching of a pipette
      deformed network. Continued progress in atomic level structure determinations of
      non-erythroid spectrin and related repeats are further complemented by
      theoretical efforts--computational approaches most notably--that have begun to
      correlate molecular scale aspects of structure with micro-mechanical measures.
      All of this recent activity in the biophysics of red cell structure-function
      challenges and refines some of the most basic tenets in cell membrane response.

PMID- 11598638
TI  - Spectrin ubiquitination and oxidative stress: potential roles in blood and
      neurological disorders.
AB  - This review covers the observations that erythrocyte spectrin has a E2 ubiquitin
      conjugating enzymatic activity that allows it to transfer ubiquitin to a target
      site in the alpha-spectrin repeats 20/21. The position of this ubiquitination
      site suggests that ubiquitination may regulate alpha beta spectrin heterodimer
      nucleation, spectrin-4.1-actin ternary complex formation, and adducin stimulated
      spectrin-actin attachment in the mature erythrocyte. In sickle cells, which
      contain altered redox status (high GSSG/GSH ratio), ubiquitin attachment to the
      E2 and target sites in alpha-spectrin is greatly diminished. We propose that this
      attenuated ubiquitination of spectrin may be due to glutathiolation of the E2
      active site cysteine leading to diminished ubiquitin-spectrin adduct and
      conjugate formation. Furthermore we propose that lack of ubiquitin-spectrin
      complex formation leads to dysregulation of the membrane skeleton in mature SS
      erythrocytes and may diminish spectrin turnover in SS erythropoietic cells via
      the ubiquitin proteasome machinery. In hippocampal neurons, spectrin is the major
      ubiquitinated protein and a component of the cytoplasmic ubiquitinated inclusions
      observed in Alzheimer's and Parkinson's diseases. The two primary neuronal
      spectrin isoforms: alpha SpI Sigma*/beta SpI Sigma 2 and alpha SpII Sigma 1/beta
      SpII Sigma 1 are both ubiquitinated. Future work will resolve whether neuronal
      spectrins also contain E2-ubiquitin conjugating activity and the molecular basis
      for formation of ubiquitinated inclusions in neurological disorders.

PMID- 11598639
TI  - Enzyme-linked immunosorbent assay in screening of leukemia-associated nuclear
      proteins.
AB  - Our previous data revealed some diversities in electrophoretic characteristics of
      nuclear fraction proteins isolated from peripheral blood mononuclear cells of B
      cell chronic lymphocytic leukemia (B-CLL) patients and healthy donors. Two
      electrophoretically-specific nuclear non-histones in the molecular mass zone of
      38/39 and 44/46 kDa of leukemic mononuclear cells were used as immunogens to
      produce rabbit antisera. The Western blot analysis indicated that both nuclear
      components are expressed only in mononuclear cells isolated from peripheral blood
      of B-CLL patients, but not in those isolated from the blood of healthy donors.
      For further investigations of nuclear fraction from normal and B-CLL mononuclear
      cells, an enzyme-linked immunosorbent assay (ELISA) was used. The results
      obtained by ELISA with the antisera raised against both electrophoretically
      specific B-CLL nuclear polypeptides revealed a different extend of cross
      reactivity of nuclear fraction preparations isolated from normal cells and those
      isolated from leukemic ones. We noticed that nuclear fraction preparations which
      originated from leukemic mononuclear cells are much more reactive than normal
      ones with both antisera (at a broad range of antisera dilutions).

PMID- 11598641
TI  - Mechanical and functional aspects of membrane skeletons.
AB  - Membrane skeletons can be characterized as cytoskeletal structures lying parallel
      to the bilayer part of cellular and organelle membranes. Typical examples are
      spectrin network and actin-myosin cortex. We approach the problem of elucidating
      the function of membrane skeletons by theoretically analyzing mechanical models
      of the cellular behavior. Membranes of different physical and chemical properties
      are considered. In erythrocytes and some organelles membrane bilayers are smooth
      and simply underlaid or overlaid by membrane skeletons. It is argued that there
      the role of a membrane skeleton is, either, to keep the membrane composition
      laterally homogeneous as it is in the case of the erythrocyte, or, that it is
      involved in the processes of the lateral separation of integral membrane proteins
      as it is happening in the case of some intermediate steps of the vesicular
      membrane trafficking. In the second type of membranes the bilayer part is ruffled
      and folded, and there the membrane skeletons play a role in the determination of
      the cortical tension. Here we explore in more detail the mechanical behavior of a
      cell with such properties of its boundary. The shape transformations are
      described which occur under the influence (i) of different external forces, i.e.,
      when an originally spherical cell is aspirated into the micropipette or when such
      a cell is adsorbed on a flat surface, and (ii) of different internal forces on
      the cell boundary exerted by the cytoskeletal elements.

PMID- 11598640
TI  - Impact of four antimutagens on apoptosis in genotoxically damaged lymphocytes in
      vitro.
AB  - An antimutagenic activity of fluphenazine, todralazine, anthocyanins and
      alkylresorcinols was established in a battery of short-term cytogenetic tests.
      One of the possible mechanisms of their antimutagenic action could be an increase
      in apoptotic elimination of heavily-damaged cells from a culture. In this paper
      we provide data on quantitative estimation of the antimutagens' impact on
      apoptosis in lymphocyte cultures exposed in the G(0)-phase to genotoxic agents:
      hydrogen peroxide (0.2mM, 20 min.) or benzo[a]pyrene (40 microM, 90 min.), and
      then cultured for 36 hrs in the presence of a lectin (PHA-M, 1% v/v) and each of
      the tested antimutagens. Apoptosis was estimated by means of microscopic
      examination of cell smears stained with a mixture of fluorochromes (ethidium
      bromide/acridine orange) as well as of the results of DNA separation with the
      field inversion gel electrophoresis. By microscopic examination we assessed that
      the frequencies of cells exhibiting morphological features of apoptosis
      considerably increased in the cultures containing the antimutagens. The FIGE
      separation of DNA from those cultures proved that the DNA content in the 30-50 kb
      domain was markedly elevated, as compared with the control cultures that did not
      contain antimutagens. It was established in the regression analysis that the
      apoptosis-enhancing effect significantly depended on the concentration of each
      tested antimutagen in a culture medium. However, marked differences of apoptosis
      enhancing potency were noticed among the four antimutagens. The multicriterial
      analysis proved that the apoptosis-enhancing effects of fluphenazine and also, to
      a smaller extent, by alkylresorcinols, were many times stronger than those of
      anthocyanins and of todralazine. The results suggest that the enhancement of
      apoptosis by fluphenazine and by alkylresorcinols can explain a major part of
      their antimutagenic activity, whereas in the case of anthocyanins and of
      todralazine other mechanisms of antimutagenic action should be sought for.

PMID- 11598642
TI  - The postsynaptic spectrin/4.1 membrane protein "accumulation machine".
AB  - An important aspect of the function of the membrane-associated cytoskeleton has
      been suggested to be to trap and retain selected transmembrane proteins at points
      on the cell surface specified by cell adhesion molecules. In the process, cell
      adhesion molecules are cross-linked to each other, and so junctional complexes
      are strengthened. In this short review, we will discuss recent advances in
      understanding the role of this "accumulation machine" in postsynaptic structures.
      Function in the brain depends on correct ordering of synaptic intercellular
      junctions, and in particular the recruitment of receptors and other apparatus of
      the signalling system to postsynaptic membranes. Spectrin has long been known to
      be a component of postsynaptic densities, and recent advances in molecular
      cloning indicate that beta spectrins at PSDs are all "long" C-terminal isoforms
      characterised by pleckstrin homology domains. Isoforms of protein 4.1 are also
      present at synapses. All four 4.1 proteins are represented in PSD preparations,
      but it is 4.1R that is most enriched in PSDs. 4.1R binds to several proteins
      enriched in PSDs, including the characteristic PSD intermediate filament, alpha
      internexin. Both 4.1 and spectrin interact with ionotropic glutamate receptors
      (AMPA and NMDA receptors, respectively): 4.1 stabilises AMPA receptors on the
      cell surface. By linking these receptors to the cytoskeletal and cell adhesion
      molecules that specify glutamatergic synapses, the membrane protein accumulation
      machine is suggested to direct the formation of postsynaptic signalling
      complexes.

PMID- 11598643
TI  - Mechanoprotection of the plasma membrane in neurons and other non-erythroid cells
      by the spectrin-based membrane skeleton.
AB  - Though the cytomechanics of spectrin have been explored only for erythrocytes, it
      is thought that the spectrin skeleton acts universally to support the otherwise
      mechanically vulnerable cell surface bilayer. Evidence for this role is beginning
      to accumulate and is reviewed here. Compared to that for erythrocytes, cells
      whose simplicity facilitates biophysical approaches, the evidence is indirect.
      One way that membrane skeleton/bilayer interactions have been probed is via the
      behavior of mechanosusceptible ion channels - channel whose gating is perturbed
      by abnormally high bilayer tension. These initially unresponsive channels become
      progressively more mechanoresponsive as stretch and chemical reagents damage the
      membrane skeleton. The straightforward implication is that the intact membrane
      skeleton is mechanoprotective. In non-erythroid cells there is continual
      trafficking of bilayer to and from the plasma membrane. Some of the traffic
      involves spectrin-lined vacuolar membrane. Several lines of evidence suggest that
      when neurons elongate and remodel their neurites, membrane skeleton-based
      mechanoprotection allows the dynamic vacuoles and the plasma membrane to
      participate in mechanosensitive surface area expansion and retrieval.

PMID- 11598644
TI  - Dynamical and structural properties of lipid membranes in relation to liposomal
      drug delivery systems.
AB  - The structural and dynamical properties of DPPC liposomes containing lipopolymers
      (PEG-lipids) and charged DPPS lipids have been studied in relation to the lipid
      membrane interaction of enzymes and peptides. The results suggest that both the
      lipid membrane structure and dynamics and in particular the appearance of small
      scale lipid structures might be of importance for the activity of membrane
      associated and liposome degrading enzymes as well as for the membrane interaction
      of acylated peptides. The combined experimental and simulation results are of
      relevance for a rational development of peptide loaded liposomal drug delivery
      systems that become destabilized by membrane degrading phospholipase A(2)
      enzymes, which are found at elevated concentrations at diseased sites.

PMID- 11598645
TI  - The response of the neuronal membrane to acetaldehyde treatment.
AB  - To assess the effects of acetaldehyde (AA) on the native synaptosomal membranes,
      we used the atomic force microscopy (AFM) and fluorescent methods. A wide range
      of concentrations (from 2 to 4000 microM) of AA was studied. The visualization of
      synaptosomes by AFM showed structural changes in the synaptosomal surface at an
      AA concentration of 50 microM, which is comparable with the AA concentrations
      occurring during ethanol intoxication. In our study, we observed that AA at small
      concentrations (up to 50 microM) considerably decreased the microviscosity of the
      hydrophobic region of the bulk membrane lipids (the ratio of the monomeric and
      excimeric probe fluorescence decreased). These findings correlate with the AFM
      study on the effect of 50 microM AA on the washed synaptosome membranes.

PMID- 11598646
TI  - The hemolytic toxicity of some new aminophosphonates.
AB  - A series of ten aminophosphonate derivatives were assayed for their hemolytic
      activity as a preliminary screening for the detection of herbicides. The data
      obtained indicate: 1. A clear correlation between the hemolytic capacity of the
      test compounds and their plant growth inhibition and an increase in membrane
      fluidity was demonstrated. 2. It was found that the most active compounds
      revealed at least one of the following structural features: an iso-propyl
      substituent at the phosphorus atom, a tert-butyl group attached to their hexane
      ring or a long hydrocarbon chain. 3. Ring substituents at the phosphorus (phenyl
      ring), carbon or nitrogen atoms (hexane) removed the hemolytic activity of
      compounds. 4. It may be concluded that the hemolytic toxicity of the
      aminophosphonates studied is related to their ability to incorporate and fuse
      into the lipid phase of the erythrocyte membrane. The general conclusion is that
      both stereochemistry and hydrophobicity are deciding factors for the efficiency
      of the interaction of the studied compounds studied with erythrocytes, and that
      the most possible location of the aminophosphonates is in the lipid phase of the
      RBC membrane.

PMID- 11598647
TI  - Metal ion-flavonoid associations in bilayer phospholipid membranes.
AB  - The complexation process of the transition (Cu(2+), Fe(2+)) and heavy (Pb(2+))
      metals with flavonoids (quercetin and rutin) was studied. The investigation was
      conducted using the spectrophotometric method in a medium containing
      phosphatidylcholine liposome membrane and in methanol. The Benesi-Hildebrand
      method was used to determine the constants of flavonoid-metal complex formation
      of the "charge transfer" type, and the Gibbs free energy change for that process.
      It was found that both quercetin and rutin are very effective at complexing
      transition atoms in both methanol and in the lipid bilayer. Pb(II) ions were only
      complexed in methanol. A short discussion is given on the importance of metal
      coordination processes in the context of lipid membrane peroxidation.

PMID- 11598648
TI  - X-ray diffraction and neutron scattering studies of amphiphile-lipid bilayer
      organization.
AB  - The lipid bilayer thickness d(L), the transbilayer distance of lipid phosphate
      groups d(pp/inf> and the lipid surface area A(L) of fluid hydrated bilayers of
      lamellar phases of egg phosphatidylcholine or dipalmitoylphosphatidylcholine
      containing N-alkyl-N,N-dimethylamine N-oxides (CnNO), 1,4-butanedi-ammonium-N,N'
      dialkyl-N,N,N',N'-tetramethyl dibromides (GSn) or mono-hydrochlorides of [2
      (alkyloxy)phenyl]-2-(1-piperidinyl)ethylesters of carbamic acid (CnA) were
      obtained by X-ray diffraction, and the bilayer thickness in extruded unilamellar
      dioleoylphosphatidylcholine vesicles containing C12NO was obtained by the neutron
      scattering. The values of d(L), d(pp/inf> and A(L) change linearly up to the 1:1
      amphiphile:lipid molar ratio. The slopes of these dependencies increase for d(L)
      and d(pp/inf> and decrease for AL) with an increasing number of carbons n in the
      amphiphile long hydrocarbon substituent (18> or =n> or =8 for CnNO, 16> or =n> or
      =9 for GSn, 12> or =n> or =5 for CnA), while the opposite trends are observed for
      the short substituent (8> or =n>/=6 for CnNO, 9> or =n> or =7 for GSn, 5> or =n>
      or =3 for CnA). In case of long substituents, the effects on dL), dpp/inf> and
      AL) are caused by the decrease in the difference between the lipid and amphiphile
      hydrocarbon chain lengths and by the increase in their van der Waals attraction.
      The short substituent amphiphiles are mobile and exchange between multiple
      binding sites in the bilayer, minimizing the bilayer surface area.

PMID- 11598649
TI  - The membrane-disrupting activity of alpha-aminoalkanephosphonic acids and their
      derivatives.
AB  - The influence of a series of acyclic and cyclic aminophosphonates on the
      physicochemical properties of model (planar lipid membranes-BLM) and biological
      (erythrocytes-RBC) membranes was studied. The results obtained were compared with
      the results of physiological tests performed on the aquatic plant Spirodela
      oligorrhiza. It was found that the inhibition of plant growth by the compounds
      studied correlated, although not very highly, with the observed changes in the
      properties of membranes used. It was also found that both the biological activity
      of aminophosphonates and their efficiency at modifying the physicochemical
      parameters of membranes depended on their structural features.

PMID- 11598650
TI  - The action of mercury on cell membranes.
AB  - The action of mercuric chloride and methyl mercuric chloride on the membrane
      lateral domain organization of bovine, equine, and canine erythrocytes was
      studied. Electron paramagnetic resonance (EPR) spectra of spin-labeled
      erythrocytes were analyzed with respect to their lateral domain structure.
      Continuous alteration of the membrane domain populations revealed that mercuric
      compounds affect the membrane via the evolution of toxic events in the cells.

PMID- 11598651
TI  - Membrane active compounds that affect the shape of cells and cellular organelles.
AB  - Amphiphilic membrane active compounds are considered that affect the shapes of
      cells and cellular organelles by intercalation into the phospholipid part of
      their membranes. It is taken into consideration that amphiphile-membrane
      interaction modifies membrane mechanical properties. The relationship between
      membrane mechanical properties and vesicle shapes and the concept of the bilayer
      couple model are shortly reviewed. Then it is put forward that the strength of
      the amphiphile-membrane interaction may depend on the lateral packing of
      phospholipid molecules. It is shown that in such a case the amphiphile molecules
      bind to the membrane in a cooperative manner. Moreover, the amphiphile binding
      makes the ratio between the nonlocal and local membrane bending constants to be
      effectively larger and thus widens the range of possible stable vesicle and
      cellular shapes.

PMID- 11598652
TI  - Cytokinin activities in cells of wheat inflorescence in depependence of its
      developmental stage.
AB  - We demonstrate that differences in the endogenous biologically active levels and
      patterns of cytokinins depend on the organ differentiation, i. e. immature
      inflorescence before meiosis and immature embryo 14 days after anthesis,
      respectively, in winter wheat of two genotypes: Grana and Almari. Two cell lines
      were subjected to analysis of cytokinin contents. Higher levels of endogenous
      cytokinin were found in cells derived from immature embryo (E) in comparison to
      cells obtained from immature inflorescence (I). The levels of zeatin ryboside
      ([9R]Z) and benzyladenosine ([9R]BAP) were predominant and isopentenyladenine
      (iP) was very low for the cells E of both genotypes. The cytokinin amounts in
      cells E and I of the zeatin group were smaller than those of other groups. We
      suggest that the concentration of cytokinins in tissue capable of generative
      development in winter wheat should be on a level that occurred in inflorescence
      cell lines, in comparison to immature embryo cell lines. These results indicate
      that the effect of the developmental stage of ears of wheat on the capability to
      flower in winter wheat plants regenerated in in vitro culture may be induced by
      the hormone level.

PMID- 11598653
TI  - Interaction of channel-blocking bispyridinium compounds with supported
      phospholipid layers.
AB  - The interaction of phospholipid monolayers of dioleoyl phosphatidylcholine (DOPC)
      on mercury electrodes with bispyridinium compounds is reported in this paper. The
      interaction is related to the modification of the capacitance-potential plot and
      in particular of two well defined phase transitions of the phospholipid
      monolayer. The order of the extent of interaction of the test compounds with the
      monolayer can be related to their structure and is:
      P65>Toxogonin>BPE>HS6>TMB4>HI6>BPT>P2S. The penetration of the compound into the
      monolayer depends on potential. At potentials more negative than the occurrence
      of the two phase transitions, the test compounds penetrate further and disrupt
      the monolayers. At more positive potentials this effect is reversed.

PMID- 11598776
TI  - Antioxidant effect of taurine against lead-induced oxidative stress.
AB  - Oxidative stress is proposed as a molecular mechanism in lead toxicity, which
      suggests that antioxidants might play a role in the treatment of lead poisoning.
      The present study was designed to investigate whether taurine has a beneficial
      effect both on Chinese hamster ovary (CHO) cells and on Fisher 344 (F344) rats
      following lead exposure. Therefore, oxidative stress parameters (glutathione,
      malondialdehyde levels, catalase, and glucose-6-phosphate dehydrogenase [G6PD]
      activities) of lead-exposed CHO cells and F344 rats were determined following
      taurine treatment. Taurine was found to be effective in (1) increasing
      glutathione levels that had been diminished by lead; (2) reducing malondialdehyde
      levels, an end-product of lipid peroxidation; (3) decreasing catalase and
      erythrocyte G6PD activity, which had been increased by lead exposure; and (4)
      improving cell survival of CHO cells. However, taurine had no effect on blood and
      tissue lead levels when 1.1 g/kg/day taurine was administered to F344 rats for 7
      days, following 5 weeks of lead exposure (2,000 ppm lead acetate). As a result,
      taurine seems to be capable of fortifying cells against lead-induced oxidative
      attack without decreasing lead levels. Therefore, administration of taurine,
      accompanied by a chelating agent, might increase its effectiveness in the
      treatment of lead poisoning.

PMID- 11598777
TI  - Protective effects of selenium against mercury toxicity in cultured Atlantic
      spotted dolphin (Stenella plagiodon) renal cells.
AB  - Marine mammals are known for their low susceptibility to mercury toxicity, and
      selenium may play a role in this protection against mercury intoxication. To gain
      insight into mechanisms by which selenium might inhibit mercury toxicity in
      cetacean cells, we investigated the effects of sodium selenite on cell
      proliferation and cell death (including apoptosis, oncosis, and necrosis) of
      control and mercuric chloride-treated Atlantic spotted dolphin renal cells (Sp1K
      cells). Concurrent exposure to 80 microM Na2SeO3 provided full protection against
      the decrease in cell proliferation induced by 20 microM HgCl2. Pretreatment with
      Na2SeO3 increased the protective effects of selenium administered later in
      conjunction with mercury, but pretreatment alone did not provide protection
      against mercury given alone. Furthermore, Na2SeO3 administered after the exposure
      to HgCl2 did not protect cells. These data suggest that the coexistence of
      Na2SeO3 and HgCl2 was essential for the protective effects of Na2SeO3 against the
      toxicity of HgCl2 in Sp1K cells, and may involve selenium-mercury binding. This
      is supported by the results of an experiment in which earlier premixed mercury
      and selenium solutions were less cytotoxic than freshly mixed solutions.
      Furthermore, HgCl2 induced apoptosis in Sp1K cells, as revealed by nuclear
      specific dye (7-AAD) incorporation and cell flow cytometry, and this was
      prevented by the concurrent exposure to Na2SeO3. Inhibition of mercury-induced
      apoptosis in marine mammal cells, provided by selenium, may contribute to the in
      vivo protection. This study is the first report that addresses the mechanism of
      mercury-selenium antagonism in cultured cetacean cells at the cellular level.

PMID- 11598778
TI  - The occurrence and distribution of selected trace elements in the Upper Rio
      Grande and tributaries in Colorado and northern New Mexico.
AB  - Two sampling trips were undertaken in 1994 to determine the distribution of trace
      elements in the Upper Rio Grande and several of its tributaries. Water discharges
      decreased in the main stem of the Rio Grande from June to September, whereas
      dissolved concentrations of trace elements generally increased. This is
      attributed to dilution of base flow from snowmelt runoff in the June samples. Of
      the three major mining districts (Creede, Summitville, and Red River) in the
      Upper Rio Grande drainage basin, only the Creede District appears to impact the
      Rio Grande in a significant manner, with both waters and sediments having
      elevated concentrations of some trace elements considerably downriver. For
      example, dissolved zinc concentrations upriver of Willow Creek, which primarily
      drains the Creede District, were about 2-3 microg/L; immediately downstream of
      the Willow Creek confluence, concentrations were above 20 microg/L; and elevated
      concentrations occurred in the Rio Grande for the next 100 km. The Red River
      District does not significantly impact the Upper Rio Grande for most trace
      elements. Because of current water management practices, it is difficult to
      assess the impact of the Summitville District on the Upper Rio Grande. There are,
      however, large increases in many dissolved trace element concentrations as the
      Rio Grande passes through the San Luis Valley, coincident with elevated
      concentrations of those same trace elements in tributaries. Among these elements
      are As, B, Cr, Li, Mn, Mo, Ni, Sr, U, and V. None of the trace elements exceeded
      U.S. EPA primary drinking water standards in either survey, with the exception of
      cadmium in Willow Creek. Secondary drinking water standards were frequently
      violated, especially in tributaries draining areas where mining has occurred.
      Dissolved zinc (in Willow Creek in both June and September) was the only element
      that exceeded the EPA Water Quality Criteria for aquatic life of 120 microg/L.

PMID- 11598779
TI  - Application of the sequential elution technique to determine Cd and Cu cellular
      location in Ulva lactuca Linnaeus.
AB  - The sequential elution technique, used to determine the cellular location of
      metals in nonvascular plants, was adapted to the seaweed Ulva lactuca Linnaeus
      for the heavy metals Cu and Cd. The optimum conditions for the extraction of
      extracellular Cu and Cd were determined using specimens previously loaded with
      these metals. The best extracellular metal extraction media and the number of
      extracellular metal extraction steps obtained were the following: Two steps (1 h
      + 40 min) in a filtered sea water-20 mM Ni solution for Cd and two steps in a
      filtered sea water-50 mM Co solution for Cu. To find these extraction conditions
      the extracellular metal extraction capacity of the different media used as well
      as the alteration provoked in plasmalemma permeability were compared. The
      concentrations of the incubation solutions of Cd and Cu that allowed reliable
      comparisons between the different extracellular metal extraction media used were
      previously determined.

PMID- 11598780
TI  - Modification, by the insecticide chlorpyrifos, of the behavioral response to
      kairomones of a parasitoid wasp, Leptopilina boulardi.
AB  - Parasitoids are key species involved in the regulation of natural populations.
      Host parasitization is realized via some important steps in which kairomone
      perception is essential. Due to the wide use of insecticides and their
      contribution to environmental pollution, the determination of their sublethal
      effects on behaviors involved in the reproduction of parasitoids becomes a
      necessity. In this work, we analyzed the effects of a lethal dose 20% of
      chlorpyrifos, an organophosphorus insecticide, on the behavior of L. boulardi
      toward the kairomone of its host. The insecticide significantly modified the
      kinetics of the residence time of parasitoids on a patch marked by kairomones.
      Females exposed to the insecticide were less efficient in finding the kairomone
      patch than control females, and they tended to stay on that patch, whereas
      control females rapidly left it. These effects are discussed considering the mode
      of action of the insecticide. Because search time allocation of host is an
      important component for parasitism efficiency, this modification of behavior
      could interfere with the reproduction capacity of parasitoids. Therefore, in a
      context of environmental pollution, the repercussions of such sublethal effects
      on the population biology of insects need to be considered.

PMID- 11598781
TI  - Chlorpyrifos-induced hsp70 expression and effect on reproductive performance in
      transgenic Drosophila melanogaster (hsp70-lacZ) Bg9.
AB  - Expression of hsp70 in the third-instar larval tissues of transgenic Drosophila
      melanogaster (hsp70-lacZ) following dietary exposure to organophosphate
      insecticide chlorpyrifos for various time intervals was investigated. Effect of
      the chemical on different developmental stages of the fly was also evaluated by
      looking at survivorship, hatchability, emergence, fecundity, fertility, and
      reproductive performance. Our results showed that the toxicant evokes profound
      cytotoxic effect as evidenced by dark blue staining in salivary gland,
      proventriculus, brain ganglia, and midgut in the lowest concentration of the
      chemical following 24 and 48 h of exposure. On the other hand, a significant
      increase (61%) in hsp70 expression in the above larval tissues was observed in
      the next higher concentration of the toxicant after 6 h exposure when compared
      with that of the lowest dose. A further increase in exposure time caused 100%
      larval mortality. Similarly, larvae exposed to higher concentrations of the
      toxicant, exhibited 100% mortality within 1 h of treatment. The insecticide
      caused a delay in emergence and a severe reduction in survivorship of the flies
      in a dose-dependent manner with 100% mortality within a day of exposure in the
      highest dosed group. A delay in emergence by 3 days was evident even in the
      lowest concentration of the chemical. A drastic effect of the chemical on
      hatchability was found in the highest dosed group with 100% embryonic mortality
      at post-16 stage of the embryo. Reproductive performance was significantly
      affected even in the lowest dosed group. The present study suggests that certain
      larval tissues of Drosophila, a nontarget organism, are vulnerable to
      chlorpyrifos as evidenced by hsp70 expression. Further, the adverse effect of the
      toxicant is reflected on various stages of development of the fly including
      reproductive performance.

PMID- 11598782
TI  - Toxicokinetics, available source, and route of entry of lead in fed and food
      deprived bullfrog (Rana catesbeiana) larvae.
AB  - Several toxic effects of lead (Pb) have been documented in amphibians, but few
      studies have measured tissue levels of exposed specimens or examined
      toxicokinetics, availability of dietary versus waterborne sources, or route of
      entry. We modeled the toxicokinetics and examined the availability of dietary and
      waterborne Pb in both fed and food-deprived bullfrog (Rana catesbeiana) larvae.
      Uptake rates of Pb (1,000 microg Pb/L nominal exposure) were similar between fed
      and unfed larvae, but unfed larvae eliminated Pb slowly. Consequently, food
      deprived larvae accumulated significantly more Pb compared to fed larvae. The
      intestinal tract contained > 90% of total body Pb in both fed and unfed larvae.
      Total body concentrations of Pb in fed larvae did not increase over 7 days
      although levels in food did increase. We concluded that food consumption
      influenced Pb accumulation through changes in elimination rates rather than in
      uptake rates. Pb appeared to enter the body of larvae through ingestion of
      contaminated water rather than food.

PMID- 11598783
TI  - Reproductive effects of ethynylestradiol and 4t-octylphenol on the zebrafish
      (Danio rerio).
AB  - In this study, the impact of ethynylestradiol (EE2) and 4t-octylphenol (OP) on
      reproduction in zebrafish (Danio rerio) was evaluated using spawning and
      fertilization success, gonadosomatic index, and plasma vitellogenin (VTG) levels
      as endpoints. Adult male and female zebrafish were exposed under semi-static
      conditions to 5, 10, 25 and 50 ng/L EE2 and to 12.5, 25, 50 and 100 microg/L OP
      for 3 weeks. A dose-related reduction in the number of females capable of
      spawning was observed at 10 ng/L EE2 with a complete inhibition of spawning at
      levels of 25 ng/L EE2. The ovaries of these nonspawning females were regressed
      and mean ovary somatic index (OSI) was significantly below the reference OSI
      determined in nonexposed females prior to spawning. Our results suggest an
      adverse impact of EE2 on male fertilization capacity and demonstrate a
      significant reduction in testis somatical index after exposure to 10 and 25 ng/L
      EE2. For both males and females, a dose dependent VTG induction was measured.
      Levels of VTG in fish plasma were significantly correlated with measured
      gonadosomatic indices. Minor effects were observed for OP. No significant effects
      on spawning or fertilization success were observed in this study, though OSI of
      nonspawning females was reduced at levels of 25 microg/L OP and higher. No
      changes in plasma protein levels were measured in male and female fish exposed to
      OP. The results from this study demonstrate that OP and especially EE2 can
      adversely affect the normal reproduction success of male and especially female
      zebrafish, with relevance for population effects.

PMID- 11598784
TI  - Tissue-specific cadmium accumulation, metallothionein induction, and tissue zinc
      and copper levels during chronic sublethal cadmium exposure in juvenile rainbow
      trout.
AB  - Juvenile rainbow trout, on 3% of body weight daily ration, were exposed to 0
      (control) or 3 microg/L Cd (as Cd(NO3)2*4H2O) in moderately hard (140 mg/L as
      CaCO3), alkaline (95 mg/L as CaCO3, pH 8.0) water for 30 days. Particular
      attention focused on Cd burden in tissues (gills, liver, kidney, and whole body)
      and induction of metallothionein (MT) in gills, liver, and kidney during chronic
      Cd exposure. Mortality in Cd-exposed fish was minimal ( approximately 10%), and
      no growth effects occurred over the 30-day exposure. Cd accumulated in a time
      dependent fashion to 9 times (gills), 3 times (liver), 20 times (kidney), 2 times
      (carcass), and 2 times (whole body) control levels by 30 days; absolute
      concentrations were in the order kidney > gill > liver > whole body > carcass.
      Tissue (gills, liver, and kidney) Zn and Cu burdens were not altered by chronic
      exposure to 3 microg/L Cd. MT concentrations in all tissues increased over the 30
      days of Cd exposure, but the increases were much less than those of Cd on a molar
      binding site basis. Absolute MT concentrations were in the order liver > kidney >
      gill, but relative increases were greatest in kidney (fourfold), followed by
      gills (twofold) and liver (1.3-fold). MT levels were sufficient to bind all Cd in
      gill, liver, and kidney under control conditions, and after chronic Cd exposure
      remained sufficient in liver and kidney, but not in gills. Total metal levels (Cd
      + Zn + Cu) greatly exceeded MT binding capacity in all tissues under all
      conditions.

PMID- 11598785
TI  - Assessment of reproductive effects in largemouth bass (Micropterus salmoides)
      exposed to bleached/unbleached kraft mill effluents.
AB  - This study evaluated the potential effects of different concentrations of
      bleached/unbleached kraft mill effluent (B/UKME) on several reproductive
      endpoints in adult largemouth bass (Micropterus salmoides). The kraft mill
      studied produces a 50/50 mix of bleached/unbleached market pulp with an estimated
      release of 36 million gal of effluent/day. Bleaching sequences were C90d10EopHDp
      and CEHD for softwood (pines) and hardwoods (mainly tupelo, gums, magnolia, and
      water oaks), respectively. Bass were exposed to different effluent concentrations
      (0 [controls, exposed to well water], 10, 20, 40, or 80%) for either 28 or 56
      days. At the end of each exposure period, fish were euthanized, gonads collected
      for histological evaluation and determination of gonadosomatic index (GSI), and
      plasma was analyzed for 17beta-estradiol, 11-ketotestosterone, and vitellogenin
      (VTG). Largemouth bass exposed to B/UKME responded with changes at the
      biochemical level (decline in sex steroids in both sexes and VTG in females) that
      were usually translated into tissue/organ-level responses (declines in GSI in
      both sexes and in ovarian development in females). Although most of these
      responses occurred after exposing fish to 40% B/UKME concentrations or greater,
      some were observed after exposures to 20% B/UKME. These threshold concentrations
      fall within the 60% average yearly concentration of effluent that exists in the
      stream near the point of discharge (Rice Creek), but are above the <10% effluent
      concentration present in the St. Johns River. The chemical(s) responsible for
      such changes as well as their mode(s) of action remain unknown at this time.

PMID- 11598786
TI  - Multi-elemental concentrations in tissues of Japanese common squid (Todarodes
      pacificus).
AB  - Forty-five elements were determined in mantle muscle and liver of juvenile
      Japanese common squid, Todarodes pacificus, collected from three locations in and
      near Japanese coasts, using a high-resolution inductively coupled plasma mass
      spectrometer (HR-ICP-MS) and an inductively coupled plasma atomic emission
      spectroscope (ICP-AES). Multivariate statistical techniques were applied to
      discriminate populations of squids from these three locations by treating
      absolute and relative concentrations of trace elements. Significant differences
      were found in the concentrations of elements, particularly for some alkaline and
      alkaline earth elements in the muscle and liver and for some 3d transition
      elements in the liver of three groups of squids. Squids from the Pacific Ocean
      could be distinguished from those of the Sea of Japan by discriminant function
      analysis of elemental concentrations. Based on the analysis, the squids collected
      from the Nemuro Strait in Japan were predicted to belong to those from the Sea of
      Japan. Elemental concentrations and discriminant function analysis can be used to
      identify subpopulations and migratory routes of squids.

PMID- 11598787
TI  - Trace elements in king eiders and common eiders in the Canadian arctic.
AB  - We determined concentrations of selected trace elements in tissues of king and
      common eiders at three locations in the Canadian arctic. Renal and hepatic
      cadmium concentrations in king eiders at a location in the eastern arctic were
      among the highest ever recorded in eider ducks: there, they were higher in king
      eiders than in common eiders. Cadmium concentrations were lower in king eiders
      from the western arctic than in those from the east. In the western arctic,
      cadmium concentrations did not differ between species. Hepatic mercury and zinc
      were higher in king eiders than in common eiders. Zinc and selenium were higher
      in eiders from the western arctic than in those from the eastern arctic. Trace
      element concentrations in these two duck species were below published toxicity
      thresholds. Positive correlations in trace element concentrations in both species
      were found between total and organic hepatic mercury, renal and hepatic cadmium
      as well as hepatic zinc, copper, mercury, and cadmium. Body mass of common but
      not king eiders and spleen mass of both species were negatively correlated with
      mercury concentrations. In common eiders, the number of nematode parasites was
      positively correlated with total and organic mercury. Histopathological evidence
      of kidney or liver lesions that are typical of trace metal poisoning was not
      found. We did not find evidence to support the hypothesis that trace metal
      exposure may be contributing to adverse effects on the health of individuals of
      these species.

PMID- 11598788
TI  - Mercury in eggs and feathers of great egrets (Ardea albus) from the Florida
      Everglades.
AB  - Great egret (Ardea albus) eggs and nestling feathers were collected for total
      mercury (THg) and methylmercury (MeHg) analysis from two colonies in the Florida
      Everglades in 1999 and 2000. THg was present in all eggs at a mean concentration
      of 0.39 +/- 0.19 microg/g fresh weight (n = 33, range = 0.08-0.86 microg/g). Egg
      THg levels did not differ significantly between colonies or years. MeHg
      concentration in eggs was 0.35 +/- 0.18 microg/g fresh weight (n = 20, range =
      0.05-0.82 microg/g,), and on average represented 85% of the THg found in the egg.
      Concentration of THg in feathers from egret nestlings, age 11-31 days, ranged
      from 1.4 to 8.6 microg/g dry weight. Feather-THg levels also did not differ
      significantly between colonies or years. THg concentrations in feathers,
      normalized based on bill length, were positively correlated to THg concentrations
      in eggs from the same clutch. Levels of THg in both eggs and feathers were lower
      in 1999 and 2000 than values reported for similar samples collected in 1993-95,
      indicating that MeHg exposure has decreased in the southern Everglades since the
      mid-1990s. THg levels in eggs and nestling feathers for the period of this study
      were below levels associated with toxic reproductive effects. Clutch size,
      fledging success, and brood size observed in this study were consistent for this
      species in the Everglades. Collectively, these results suggest that MeHg was not
      adversely affecting the reproductive performance of this population during the
      study.

PMID- 11598789
TI  - Uptake and distribution of three PCB congeners and endosulfan by developing white
      leghorn chicken embryos (Gallus domesticus).
AB  - The distributions of PCB 105, 156, 189, and endosulfan in incubating, maternally
      exposed, viable white leghorn chicken eggs (Gallus domesticus) were investigated.
      Hens were subcutaneously injected every 4 days with a mixture of the above
      chemicals. One group of five eggs was removed from the incubator at each of 9,
      14, and 19 days of incubation; dissected into three compartments (embryo,
      chorioallantoic membrane, and yolk + albumin); weighed; frozen; and then later
      analyzed for the dosing chemicals. Through 19 days of development (90% of
      incubation), greater than 70% of the total chemical mass in the whole egg
      remained within the yolk + albumin, whereas, depending on the chemical, 17% to
      30% was absorbed by the embryo and 0.2% to 9% was transported into the
      chorioallantoic membrane. As a percentage of total PCB mass within the respective
      compartment, PCB 105 composition in the embryo and chorioallantoic membrane
      decreased significantly throughout development while PCB 156 and 189 composition
      increased significantly throughout development. Though endosulfan composition
      within any of the compartments was highly variable, it did not change
      significantly during development. The results of this study indicate that the
      majority of avian chick exposure to contaminants occurs posthatch as the chick
      continues to utilize the residual yolk.

PMID- 11598790
TI  - Developmental instability in a riparian population of the Algerian mouse(Mus
      spretus) associated with a heavy metal-polluted area in central Portugal.
AB  - The adverse effects of heavy metals (mostly Cr, Mn, Fe, Cu, Zn, and Se) on the
      environment were appraised by comparing fluctuating asymmetry of dental
      characters (molars) in Algerian mice (Mus spretus) from polluted (Oeiras) and
      reference (Xevora) riparian areas, in central Portugal. The size of tooth traits
      was shown to be reduced in the contaminated area, and the developmental
      instability increased. The results suggest that Algerian mice may be used as
      indicators of heavy metal pollution and that fluctuating asymmetry represents a
      useful tool for monitoring ecological stresses, even when the contamination
      levels are low.

PMID- 11598791
TI  - Evaluation of the toxic potentials of cypermethrin pesticide on some reproductive
      and fertility parameters in the male rats.
AB  - Adult male Sprague-Dawley rats were exposed to tap water containing 0, 8,571,
      17,143, or 34,286 ppm cypermethrin for 12 weeks. Based on water consumption per
      animal per day the rats received 13.15, 18.93, and 39.66 mg cypermethrin,
      respectively. Fertility was significantly reduced in male rats ingesting
      cypermethrin at a concentration of 13.15 and 18.93 mg in that the number of
      females impregnated by them was significantly reduced. The number of implantation
      sites was significantly reduced in females mated with males that had ingested
      cypermethrin at a concentration of 39.66 mg. A significant reduction in the
      number of viable fetuses was observed in females impregnated by the exposed males
      at all three doses of cypermethrin. The body weight gain was significantly lower
      in the treated males. Ingestion of cypermethrin at a concentration of 18.93 or
      39.66 mg per day resulted in a significant increase in the weights of testes and
      seminal vesicles. Preputial gland weights were increased at all three
      concentrations of cypermethrin. Epididymal and testicular sperm counts as well as
      daily sperm production were significantly decreased in exposed males. The serum
      levels of testosterone, follicle-stimulating hormone and luteinizing hormone were
      significantly reduced in males exposed to 39.66 mg per day. Ingestion of
      cypermethrin at 18.93 and 39.66 mg/animal/day also resulted in a significant
      decrease in the perimeter and number of cell layers of the seminiferous tubules.
      The testes of treated animals were infiltrated with congested blood vessels with
      marked hemorrhage and a significant accumulation of connective tissue surrounding
      the seminiferous tubules, which contained a large number of immature spermatids.
      These results clearly demonstrate the adverse effects of cypermethrin pesticide
      on fertility and reproduction in male rats.

PMID- 11598793
TI  - 'What nourishes me, destroys me': towards a new mitochondrial biology.

PMID- 11598792
TI  - Effects of exposure time, material type, and granular pesticide on glove
      contamination.
AB  - Chemical-resistant gloves are recommended for pesticide applicators to reduce
      their exposure to agricultural chemicals. In this research, three chemical
      resistant glove materials-nitrile, neoprene, and barrier laminate-were studied in
      relation to contamination with granular terbufos and tefluthrin. Surfaces of
      specimens backed with alpha cellulose were contaminated with 300 mg of either
      granular terbufos or tefluthrin for 1-, 2-, 4-, 8-, 16-, and 24-h time periods in
      petri dishes in the laboratory. Residues were extracted using ethyl acetate for
      terbufos and iso-octane for tefluthrin in test tubes for 24 h. Analysis of
      extracts by gas chromatograph and statistical analysis of the data showed that
      contamination levels varied with the time of exposure, material type, and
      pesticide used. Pesticide was not detected in the alpha cellulose even after 24 h
      contamination time. A linear relationship was found between contamination level
      and exposure time for terbufos in the three materials, with longer exposure times
      causing higher contamination levels. Contamination of nitrile was significantly
      less than neoprene or barrier laminate. Exposed glove materials contained higher
      levels of contamination of terbufos than tefluthrin.

PMID- 11598794
TI  - Down-modulation of c-myc expression by phorbol ester protects CEM T leukaemia
      cells from starvation-induced apoptosis: role of ornithine decarboxylase and
      polyamines.
AB  - Myc is a transcriptional activator whose deregulated expression not only promotes
      proliferation but also induces or sensitizes cells to apoptosis. Here we
      demonstrate that c-myc plays a role in triggering apoptosis in CEM T leukaemia
      cells exposed to progressive medium exhaustion. Indeed starved cells undergo
      apoptosis in the presence of constitutively elevated c-myc expression and the
      phorbol ester, phorbol 12-miristate 13-acetate (PMA), which rescues cells from
      apoptosis, induces complete c-myc down-regulation. We also investigate the
      hypothesis that ornithine decarboxylase (ODC), a transcriptional target of c-myc,
      is a down-stream mediator of c-myc driven apoptosis. We demonstrate that PMA
      induces in starved cells an earlier and larger decrease in ODC expression (mRNA
      and activity) and intracellular polyamine content, compared to untreated starved
      cells. Moreover we show that alpha-difluoromethylornithine (DFMO), an
      irreversible inhibitor of ODC enzymatic activity, effectively reduces, while
      exogenous added polyamines enhance apoptosis in starved cells. All these data
      indicate that ODC and polyamines may act as facilitating factors in triggering
      apoptosis induced by growth/survival factors withdrawal.

PMID- 11598795
TI  - VCP/p97 in abnormal protein aggregates, cytoplasmic vacuoles, and cell death,
      phenotypes relevant to neurodegeneration.
AB  - Neuronal cell death, abnormal protein aggregates, and cytoplasmic vacuolization
      are major pathologies observed in many neurodegenerative disorders such as the
      polyglutamine (polyQ) diseases, prion disease, Alzheimer disease, and the Lewy
      body diseases, suggesting common mechanisms underlying neurodegeneration. Here,
      we have identified VCP/p97, a member of the AAA+ family of ATPase proteins, as a
      polyQ-interacting protein in vitro and in vivo, and report on its
      characterization. Endogenous VCP co-localized with expanded polyQ (ex-polyQ)
      aggregates in cultured cells expressing ex-polyQ, with nuclear inclusions in
      Huntington disease patient brains, and with Lewy bodies in patient samples.
      Moreover, the expression of VCP mutants with mutations in the 2nd ATP binding
      domain created cytoplasmic vacuoles, followed by cell death. Very similar
      vacuoles were also induced by ex-polyQ expression or proteasome inhibitor
      treatment. These results suggest that VCP functions not only as a recognition
      factor for abnormally folded proteins but also as a pathological effector for
      several neurodegenerative phenotypes. VCP may thus be an ideal molecular target
      for the treatment of neurodegenerative disorders.

PMID- 11598796
TI  - Caspase inhibition supports proper gene expression in ex vivo mouse limb
      cultures.
AB  - We standardized conditions for ex vivo mouse limb culture to study cartilage
      maturation and joint formation. We compared 12.5 d.p.c. mouse forelimbs that were
      cultured either mounted or freely rotating for up to 72 h. Limb outgrowth
      progressed ex vivo at a variable rate as compared to its development in vivo,
      spanning approximately 48 h. Although cartilage maturation and joint formation
      developed grossly normal, aberrant expression of skeletal marker genes was seen.
      Interestingly, no regression of the interdigital webs took place in mounted
      cultures, in contrast to limited webbing under freely rotating conditions.
      Caspase inhibition, by addition of zVAD-fmk to the culture medium of freely
      rotating limbs, supported proper gene expression associated with skeletal
      development, and prevented interdigital web regression. Taken together, a freely
      rotating ex vivo culture for mouse limb outgrowth that is combined with caspase
      inhibition provides a good model to study cartilage maturation and joint
      formation.

PMID- 11598797
TI  - The mechanism of mitochondrial membrane potential retention following release of
      cytochrome c in apoptotic GT1-7 neural cells.
AB  - The relationship is investigated between mitochondrial membrane potential (Delta
      Psi(M)), respiration and cytochrome c (cyt c) release in single neural bcl-2
      transfected cells (GT1-7bcl-2) or GT1-7puro cells during apoptosis induced by
      staurosporine (STS). Bcl-2 inhibited the mitochondrial release of cyt c and
      apoptosis. Three different cell responses to STS were identified in GT1-7puro
      cells: (i) neither Delta Psi(M) nor cyt c were significantly affected; (ii) a
      decrease in Delta Psi(M) was accompanied by a complete release of cyt c; or (iii)
      cyt c release occurred independently of a loss of Delta Psi(M). The endogenous
      inner membrane proton leak of the in situ mitochondria, monitored by respiration
      in the presence of oligomycin, was increased by STS by 92% in puro cells, but by
      only 23% in bcl-2 cells. STS decreased respiratory capacity, in the presence of
      protonophore, by 31% in puro cells and by 20% in bcl-2 cells. In the absence of
      STS, oligomycin hyperpolarized mitochondria within both puro and bcl-2
      transfected cells, indicating that the organelles were net generators of ATP.
      However after 15 h exposure to STS oligomycin rapidly collapsed residual
      mitochondrial polarization in the puro cells, indicating that Delta Psi(M) had
      been maintained by ATP synthase reversal. bcl-2 cells in contrast, maintained
      Delta Psi(M) until protonophore was added. These results indicate that the
      maintenance of Delta Psi(M) following release of cyt c may be a consequence of
      ATP synthase reversal and cytoplasmic ATP hydrolysis in STS-treated GT1-7 cells.

PMID- 11598798
TI  - Glutamine deprivation-mediated cell shrinkage induces ligand-independent CD95
      receptor signaling and apoptosis.
AB  - Cell shrinkage and loss of cell viability by apoptosis have been examined in
      cultured CD95(Fas/Apo-1)-expressing leukemia-derived CEM and HL-60 cells
      subjected to acute deprivation of glutamine, a major compatible osmolyte engaged
      in cell volume control. Glutamine deprivation-mediated cell shrinkage promoted a
      ligand-independent activation of the CD95-mediated apoptotic pathway. Cell
      transfection with plasmids expressing FADD-DN or v-Flip viral proteins pointed to
      a functional clustering of CD95 receptors at the cell surface with activation of
      the 'extrinsic pathway' caspase cascade. Accordingly, cell shrinkage did not
      induce apoptosis in CD95 receptor-negative lymphoma L1210 cells. Replacement of
      glutamine with surrogate compatible osmolytes counteracted cell volume decrement
      and protected the CD95-expressing cells from apoptosis. A glutamine deprivation
      dependent cell shrinkage with activation of the CD95-mediated pathway was also
      observed when asparaginase was added to the medium. Asparagine depletion had no
      role in this process. The cell-size shrinkage-dependent apoptosis induced by
      glutamine restriction in CD95-expressing leukemic cells may therefore be of
      clinical relevance in amidohydrolase enzyme therapies.

PMID- 11598800
TI  - Intracellular water motion decreases in apoptotic macrophages after caspase
      activation.
AB  - Triggering of the macrophage cell line RAW 264.7 with lipopolysaccharide and
      interferon-gamma promoted apoptosis that was prevented by inhibitors of type 2
      nitric oxide synthase or caspase. Using (1)H NMR analysis, we have investigated
      the changes of the intracellular transverse relaxation time (T(2)) and apparent
      diffusion coefficient (ADC) as parameters reflecting the rotational and
      translational motions of water in apoptotic macrophages. T(2) values decreased
      significantly from 287 to 182 ms in cells treated for 18 h with NO-donors. These
      changes of T(2) were prevented by caspase inhibitors and were not due to
      mitochondrial depolarization or microtubule depolymerization. The decrease of the
      intracellular values of T(2) and ADC in apoptotic macrophages was observed after
      caspase activation, but preceded phosphatidylserine exposure and nucleosomal DNA
      cleavage. The changes of water motion were accompanied by an enhancement of the
      hydrophobic properties of the intracellular milieu, as detected by fluorescent
      probes. These results indicate the occurrence of an alteration in the
      physicochemical properties of intracellular water during the course of apoptosis.

PMID- 11598799
TI  - Inhibition of histone deacetylase activity enhances Fas receptor-mediated
      apoptosis in leukemic lymphoblasts.
AB  - We recently reported that butyrate, an inhibitor of histone deacetylases, is
      capable of inducing Fas-independent apoptosis in the acute lymphoblastic leukemia
      cell line CCRF-CEM. Here we demonstrate that butyrate enhances Fas-induced
      apoptosis in this cell line. The application of different histone deacetylase
      inhibitors revealed that tetra-acetylated histone H4 is associated with the
      amplifying effect of butyrate on Fas-induced cell death. FasL, Fas, FADD, RIP,
      caspase-8, caspase-3, Bid, FLIP(S+L), FLASH and FAP-1, proteins known to act
      within the Fas-apoptosis cascade, showed no changes in their expression levels in
      cells treated with butyrate compared with untreated cells. Analyses of Fas
      oligomerization and Western blotting as well as enzyme activity assays of caspase
      2, caspase-3 and caspase-8 suggest that butyrate enhances Fas-induced apoptosis
      downstream of Fas but upstream of caspase-8 activation. In immunoprecipitation
      experiments a 37 kD butyrate-regulated protein was detected which specifically
      interacts with caspase-8.

PMID- 11598801
TI  - ASK1 resistant neuroblastoma is deficient in activation of p38 kinase.
AB  - Apoptosis Signal-regulating Kinase 1 (ASK1) is known to either induce apoptosis
      or differentiation in various cell lines of neuronal origin. We analyzed the
      effect of the constitutively active mutant of ASK1 (ASK1-Delta N) in an
      adenoviral vector in four neuroblastoma cell lines, two murine, C1300 and NXS2,
      and two human, SH-SY5Y and IMR-32. Already after 24 h upon infection, C1300 and
      SH-SY5Y cells arrested in growth when judged by [(3)H]thymidine incorporation,
      and the majority of the cells demonstrated apoptotic appearance, which was
      confirmed by DNA-laddering in gel electrophoresis. In contrast, NXS2 and IMR-32
      cell lines remained unaffected. Immunoblotting revealed strongly phosphorylated
      p38 MAPK accompanied by weakly phosphorylated JNK in C1300 and SH-SY5Y, whereas
      none of these kinases were activated by adenoviruses expressing the kinase
      negative ASK1 mutant or beta-galactosidase. There was no expression of
      phosphorylated kinases in IMR-32 cells, but NXS2 showed a faint band of
      phosphorylated p38 MAPK. Addition of the p38 MAPK specific inhibitor, SB203580,
      protected C1300 and SH-SY5Y cells from apoptosis induced by ASK1-Delta N. The
      anti-neoplastic agent, paclitaxel, activates ASK1 and JNK, and promotes the in
      vitro assembly of stable microtubules. Addition of 10 nM paclitaxel sensitised
      the NXS2 cell line to ASK1-induced cell death. Our results indicate that ASK1
      induces apoptosis in neuroblastoma cells mainly via the p38 MAPK pathway, and
      resistant neuroblastoma cells can be sensitised to ASK1 by paclitaxel.

PMID- 11598802
TI  - Induction of apoptosis in AK-5 tumor cells by a serum factor from tumor rejecting
      animals: cytochrome c release independent of Bcl-2 and caspases.
AB  - The ability to selectively induce apoptosis in tumor cells is the prime goal in
      cancer immunotherapy and aims at identifying potential molecular targets,
      regulating this process. Here we show that the sera from the animals which had
      spontaneously rejected the AK-5 tumor (a rat histiocytoma) had an effective and
      potent ability to counteract and kill tumor cells by inducing apoptosis, with a
      high degree of specificity. Apoptosis induced by the serum factor involved the
      activation of caspases and cytochrome c release to the cytosol. A reduction in
      mitochondrial transmembrane potential (Delta psi(m)) occurred considerably later
      than cytochrome c translocation. The anti-apoptotic protein Bcl-2 and the
      pancaspase inhibitor zVAD-fmk did not prevent cytochrome c release, but
      completely blocked the reduction in Delta psi(m), DNA fragmentation and
      apoptosis. Cyclosporin A (CsA), an inhibitor of the mitochondrial permeability
      transition (MPT) pore had no effect on cytochrome c release and apoptosis
      mediated by serum factor in AK-5 cells, suggesting that apoptosis was independent
      of MPT. Taken together these results suggest that the serum factor in conjunction
      with the immune cells may be participating in the efficient rejection of the
      tumor in syngeneic hosts and Delta psi(m) disruption but not cytochrome c
      release, is a critical and decisive event to trigger apoptotic cell death induced
      by the serum factor in AK-5 tumor cells.

PMID- 11598803
TI  - The polar polysaccharide capsule of Hyphomonas adhaerens MHS-3 has a strong
      affinity for gold.
AB  - Select groups of bacteria, including prothescate species, have an unusual
      capacity to sequester gold and bioconcentrate it to very high levels. Hyphomonas
      adhaerens MHS-3 (MHS-3) is one such species, as demonstrated by Energy Dispersive
      Spectroscopy. Transmission electron microscopy revealed that the binding site was
      specific on the polar polysaccharide capsule. A capsuleless mutant and periodate
      treated wild type did not sequester gold. The gold may interact with the same
      sites in the capsule that naturally adhere MHS-3 to surfaces in the marine
      environment.

PMID- 11598804
TI  - Influence of nutritional and environmental factors on polysaccharide production
      by Azotobacter vinelandii cultured on 4-hydroxybenzoic acid.
AB  - The capacity of 4-hydroxybenzoic acid to support exopolysaccharide (EPS)
      biosynthesis was investigated. Carbon source concentration, nitrogen
      supplementation, and other nutritional and environmental factors were optimized
      to obtain maximal EPS recovery. Higher EPS yields were obtained in nitrogen-free
      media amended with 20-30 mM 4-hydroxybenzoic acid. In general, modifications in
      inorganic salt concentration did not alter EPS production, except in the case of
      magnesium ions. Increased levels of this cation were correlated to greater EPS
      yields. Production was strongly influenced by certain environmental factors.
      Optimal values of 34 degrees C, 80 rpm and neutral or slightly basic conditions
      were selected. Under these conditions, more than 25% of the carbon source
      supplied was converted to EPS and the production was improved about 42% in
      comparison to that observed in the initial media.

PMID- 11598805
TI  - Anaerobic biodegradation of pentachlorophenol in mixtures containing cadmium by
      two physiologically distinct microbial enrichment cultures.
AB  - Anaerobic biodegradation of pentachlorophenol (PCP), in mixtures containing
      cadmium (Cd), by sulfidogenic (SRB) and methanogenic (MET) enrichment cultures,
      was studied. Removal of 91-93% of PCP occurred in both SRB- and MET-enriched
      cultures, in the absence of Cd, within 82 days. The presence of soluble Cd
      initially decreased the rate of PCP removal by the enrichment cultures, but PCP
      removal rates improved as the Cd precipitated. GC-MS, 14C-PCP, and 13C-PCP
      studies confirmed mineralization of PCP by both enrichment cultures, as well as
      the incorporation of PCP carbon into specific phospholipid fatty acids (PLFAs) of
      the cell membranes of PCP-degrading anaerobes. This is the first report on
      anaerobic biodegradation of PCP by SRB- and MET-enriched cultures in the
      presence, with simultaneous precipitation, of the toxic heavy metal Cd, and of
      the incorporation of PCP carbons into specific PLFAs of the anaerobic bacterial
      cells.

PMID- 11598806
TI  - Fermentation of glycerol by Clostridium pasteurianum--batch and continuous
      culture studies.
AB  - The fermentation of glycerol by Clostridium pasteurianum was studied with respect
      to product formation as influenced by the culture conditions. In the majority of
      batch cultures, butanol was the main fermentation product, but a varying fraction
      of glycerol was also converted to 1,3-propanediol, butyric and acetic acids and
      ethanol. More than 60 g/l glycerol was utilized, and up to 17 g/l butanol was
      produced. Fed-batch cultures did not offer an advantage. When molecular nitrogen
      was used as a nitrogen source, the fermentation time was prolonged by a factor of
      1.5. Fermentations at constant pH values between 4.5 and 7.5 did not reveal
      significant differences in product formation except for an increase in the
      ethanol content starting at pH 6.5. Chemostat cultures also yielded predominantly
      n-butanol, but in some fermentations, the 1,3-propanediol fraction was relatively
      high. The pH auxostat cultures, which were operated at a glycerol excess,
      contained 1,3-propanediol as the main product. As a whole, the fermentations were
      characterized by a certain variability in product formation under seemingly equal
      or slightly varied conditions. It appears that the regulation of the numerous
      fermentation pathways occurring in this organism is not very strict.

PMID- 11598808
TI  - Maltotriose fermentation by Saccharomyces cerevisiae.
AB  - Maltotriose, the second most abundant sugar of brewer's wort, is not fermented
      but is respired by several industrial yeast strains. We have isolated a strain
      capable of growing on a medium containing maltotriose and the respiratory
      inhibitor, antimycin A. This strain produced equivalent amounts of ethanol from
      20 g l(-1) glucose, maltose, or maltotriose. We performed a detailed analysis of
      the rates of active transport and intracellular hydrolysis of maltotriose by this
      strain, and by a strain that does not ferment this sugar. The kinetics of sugar
      hydrolysis by both strains was similar, and our results also indicated that yeast
      cells do not synthesize a maltotriose-specific alpha-glucosidase. However, when
      considering active sugar transport, a different pattern was observed. The
      maltotriose-fermenting strain showed the same rate of active maltose or
      maltotriose transport, while the strain that could not ferment maltotriose showed
      a lower rate of maltotriose transport when compared with the rates of active
      maltose transport. Thus, our results revealed that transport across the plasma
      membrane, and not intracellular hydrolysis, is the rate-limiting step for the
      fermentation of maltotriose by these Saccharomyces cerevisiae cells.

PMID- 11598807
TI  - Chromosomal integration of the Vitreoscilla hemoglobin gene in Burkholderia and
      Pseudomonas for the purpose of producing stable engineered strains with enhanced
      bioremediating ability.
AB  - Using the pUT-miniTn5 vector system developed by the laboratory of K.N. Timmis,
      the Vitreoscilla hemoglobin gene (vgb) was integrated into the chromosomes of
      Pseudomonas aeruginosa and Burkholderia cepacia; Vitreoscilla hemoglobin (VHb)
      was expressed at 8.8 and 0.8 nmol/g wet weight of cells in the respective
      engineered strains. The vgb-bearing P. aeruginosa outgrew wild-type P. aeruginosa
      and degraded benzoic acid faster than the latter strain at both normal and low
      aeration. In contrast, the vgb-bearing B. cepacia strain had a growth advantage
      over the wild-type strain at ca. 90 ppm, but not at ca. 120 ppm 2,4
      dinitrotoluene (DNT); no difference in DNT degradation was seen between the two
      strains at either normal or low aeration. The results demonstrate the
      practicality of enhancing bioremediation with vgb stably integrated into the
      chromosome, but also suggest that a minimal level of VHb expression is required
      for its beneficial effects to be seen.

PMID- 11598809
TI  - Changes in steady state on introduction of a Lactobacillus contaminant to a
      continuous culture ethanol fermentation.
AB  - Lactobacillus paracasei was introduced as a contaminant into a multistage
      continuous culture ethanol fermentation system at ratios of 1:100, 1:1, and 70:1
      with Saccharomyces cerevisiae, but failed to overtake the yeast. None of the
      inoculation ratios allowed L. paracasei to affect S. cerevisiae in the first
      fermentor in the multistage system. S. cerevisiae remained constant at
      approximately 3x10(7) CFU/ml regardless of the bacterial inoculation level, and
      even at the 70:1 inoculation ratio, glucose, ethanol, and lactic acid
      concentrations did not change from the steady-state concentrations seen before
      bacterial inoculation. However, L. paracasei decreased steadily from its initial
      inoculation level of approximately 2.2x10(9) CFU/ml and stabilized at 3.7x10(5)
      CFU/ml after 10 days of steady-state operation. Both organisms then persisted in
      the multistage system at an approximate L. paracasei/S. cerevisiae ratio of 1:100
      which confirms that, in continuous fuel ethanol production, it would be difficult
      to eliminate this bacterium. Only when the pH was controlled at 6.0 in fermentor
      1 (F1) were changes seen which would affect the multistage system. Ethanol
      concentration then decreased by 44% after 4 days of pH-controlled operation. This
      coincided with an increase in L. paracasei to >10(10) CFU/ml, and a 4x increase
      in lactic acid concentration to 20 g/l. When the clarified contents from other
      fermentors (F2-F5) in the multistage system were used as growth media, L.
      paracasei was not able to grow in batch culture. This indicated that the first
      fermentor in the multistage system was the only fermentor capable of supporting
      the growth of L. paracasei under the described conditions.

PMID- 11598810
TI  - Influence of dimethylsulfoxide on tylosin production in Streptomyces fradiae.
AB  - The polyketide aglycone, tylactone (protylonolide), does not normally accumulate
      during tylosin production in Streptomyces fradiae, suggesting that the capacity
      of the organism to glycosylate tylactone exceeds the capacity for polyketide
      synthesis. Consistent with this model, tylosin yields were significantly
      increased (due to bioconversion of the added material) when exogenous tylactone
      was added to fermentations. However, tylosin yield improvements were also
      observed (albeit at lower levels) in solvent controls to which dimethylsulfoxide
      (DMSO) was added. At least in part, the latter effect resulted from stimulation
      of polyketide metabolism by DMSO. This was revealed when the solvent was added to
      fermentations containing the tylA mutant, S. fradiae GS14, which normally
      accumulates copious quantities of tylactone.

PMID- 11598811
TI  - Ethanol production from starch by immobilized Aspergillus awamori and
      Saccharomyces pastorianus using cellulose carriers.
AB  - A simultaneous saccharification and fermentation (SSF) process was investigated
      to produce ethanol using two kinds of cellulose carriers that were respectively
      suitable for immobilization of Aspergillus awamori and Saccharomyces pastorianus.
      The maximum ethanol concentration attained by the batch operation was 25.5 g l(
      1). Under suitable conditions, both cellulose carriers with immobilized cells
      could be reused efficiently for three cycles. The total amount of ethanol
      production was 66.0 g (per 1 l working volume) after the repeated operation.
      Ethanol productivity mainly depends on a saccharification process. There is a
      limit in durability in the repeated batch operation, and it is important to
      maintain high activity of the fungus in order to produce ethanol efficiently.

PMID- 11598812
TI  - Effects of methanol on expression of an anticoagulant hirudin in recombinant
      Hansenula polymorpha.
AB  - A series of batch, fed-batch, and continuous cultures was carried out to analyze
      the effects of methanol on the fermentation characteristics of recombinant
      Hansenula polymorpha for the production of hirudin, an anticoagulant. Hirudin
      expression efficiencies were greatly influenced by the methanol concentrations in
      continuous and fed-batch culture modes. At a steady state of continuous culture,
      an optimum methanol concentration of 1.7 g l(-1) was determined at a dilution
      rate of 0.18 h(-1) with 1.8 mg l(-1) h(-1) hirudin productivity.

PMID- 11598814
TI  - Importance of chin evaluation and treatment to optimizing neck rejuvenation
      surgery.
AB  - The chin is the keystone linking the aesthetics of the face and neck but is often
      neglected in the analysis. Procedures related to the chin play an important role
      in defining neck anatomy. Alloplastic implants can provide the illusion of a
      longer jaw line in a patient with retrogenia. Even greater anatomic changes to
      the neck result when a sliding genioplasty is performed. This effect is primarily
      due to the digastric attachments from the mentum and mastoid. Advancing the
      mentum may have a more direct effect of elevating the position of the hyoid,
      which sharpens the angle between the jaw and neck. Finally, the diagnosis of a
      witch's chin is also discussed for the patients who present for aging neck
      surgery.

PMID- 11598813
TI  - Isolation and biological activity of frankiamide.
AB  - An antibiotic produced by the symbiotic actinomycete Frankia strain AiPs1 was
      isolated from culture broth using optimized thin-layer chromatography and high
      performance liquid chromatography (HPLC) methods. The novel compound that was
      isolated, dubbed frankiamide, displayed antimicrobial activity against all 14
      Gram-positive bacterial strains and six pathogenic fungal strains tested. The
      pathogenic actinomycete Clavibacter michiganensis and the oomycete Phytophthora
      were especially susceptible. In addition to displaying antimicrobial activity,
      frankiamide also strongly inhibited 45Ca(2+) fluxes in clonal rat pituitary GH4C1
      tumor cells and was comparable to a frequently used calcium antagonist, verapamil
      hydrochloride. The results of HPLC analysis, supported by both nuclear magnetic
      resonance and mass spectroscopy studies, showed that frankiamide has a high
      affinity for Na(+) ions.

PMID- 11598815
TI  - Rejuvenation of the aging neck.
AB  - Patients seeking rejuvenation of the face are influenced by youthful faces
      commonly seen in the media and entertainment world. Although standards of beauty
      evolve over time, classical facial features such as symmetry, high cheek bones,
      and an angular jaw-neck line remain as ideals. As the human face ages, a
      relatively consistent series of anatomic events occurs. Although the rate of
      change varies from person to person, the process of facial aging is predictable.
      This process involves a loss of tone of the elastic fibers of the face, resulting
      in sagging of the skin and soft tissues of the face and neck. Additionally, aging
      of the lower face often includes ptosis of the soft tissues of the chin and
      banding or cording of the muscles of the anterior neck. Aesthetic rejuvenation of
      the face and neck involves repositioning of poorly supported soft tissues. To
      accurately treat facial aging, an individualized diagnosis and anatomically based
      problem list is compiled. This should include analysis of the skin quality, bone
      structure, amount and distribution of subcutaneous fat, and relationship of the
      superficial muscles to the overlying skin. After a detailed diagnosis is made, a
      surgical treatment plan is outlined to improve the face and restore a youthful
      appearance. This article describes the applied anatomy associated with facial
      aging and explains the author's specific techniques to obtain a natural
      postoperative appearance. Avoidance of common problems associated with aging face
      surgery is emphasized.

PMID- 11598816
TI  - Surgical options for aesthetic enhancement of the neck.
AB  - A slender neckline is recognized as an attractive feature of youth. With aging,
      laxity develops in the skin and subcutaneous tissues that results in blunting of
      the cervicomental angle. Many surgical options are available to restore
      definition to the neck region. This article reviews the methods used to evaluate
      the appearance of the mentocervical area and also outlines the algorithm used by
      the senior author to surgically enhance its appearance.

PMID- 11598817
TI  - Treatment of neck laxity with a Gore-Tex cervical sling for patients with heavy
      neck tissues.
AB  - Treatment of neck laxity is a challenging problem for facial plastic surgeons.
      Many factors may contribute to this problem, including relaxation of the SMAS-
      platysma complex, excess submental adipose tissue, loss of skin elasticity, and
      anatomic factors such as hyoid position. Patients with heavy tissues in the neck
      area are more likely to have disappointing or short-lived results from neck
      rejuvenation surgery. Placement of an expanded-polytetrafluoroethylene (Gore-Tex)
      cervical sling provides additional support to the soft tissues of the neck,
      improving both initial and long-term cervical contours. This method is used in
      our practice for most patients with heavy neck tissues undergoing lower facial
      rejuvenation procedures. The cervical sling is well tolerated and provides the
      additional benefit of easy adjustability should the soft tissues of the neck
      further relax.

PMID- 11598818
TI  - Surgical treatment of the aging neck.
AB  - To obtain consistently successful results, surgical treatment of the aging neck
      must be based upon a comprehensive anatomic diagnosis, using an appropriate sense
      of cervicofacial aesthetics and taking into account the relative contributions of
      each structural component of the deformity. The degree to which the projection
      and contour of the anterior mandible, redundancy of cervical skin, presence of
      excess submental fat, hyoid bone position, and configuration of the platysma
      muscles affect the appearance of the neck should be determined preoperatively to
      develop an effective surgical plan. Experience has shown that extensive incisions
      in the region of the anterior neck and transection of the platysma should be
      avoided. Depending upon the specific findings, any combination of a group of
      procedures may be required, including cervical rhytidectomy, submental suction
      assisted lipectomy, chin augmentation, and midline imbrication of the platysma
      muscles. The indications, limitations, and possible complications of each
      procedure are described, and some technical considerations are discussed.

PMID- 11598819
TI  - Comprehensive approach to rejuvenation of the neck.
AB  - A comprehensive rejuvenation of the neck depends on accurate analysis of the
      lower face and neck with attention to the contours and deep-lying structures.
      Although many surgeons address the well-recognized changes in skin and soft
      tissue that occur with aging, we believe bone resorption is also an important
      component. Loss of bone volume leads to loss of support for the soft tissues of
      the face. The result is soft tissue ptosis and loss of angularity between the
      various planes of the face. Initially, there is loss of the submental shadow and
      loss of height of the mandibular ramus. The gonial angle loses its prominence,
      and the chin becomes ptotic. The line of the body of the mandible is further
      obscured by the appearance of jowls. As the mandible shrinks, the submandibular
      gland as well as the muscles that make up the floor of the mouth are pushed
      inferiorly. For loss of bone support, implants tailored to the areas of deficit
      and to the aesthetic goals are used. These implants used for the mandible are
      tridimensional structures made from beaded polyethylene material. This restores
      the bone volume and provides good support for the soft tissues. We routinely
      perform a deep-layer cervicoplasty. This involves removing fat from the
      subplatysmal layer and between the anterior bellies of the digastric muscles. The
      digastric muscles are plicated toward the midline. The platysma muscle is
      separated from the underlying submandibular gland. Ptosis of the submandibular
      gland is treated by suspension of the fascia with sutures or imbrication of the
      overlying muscle. A short corset platysmaplasty brings the platysma muscles to
      the midline. Above the level of the hyoid bone, the digastric muscles are
      included in the sutures. If the patient has an obtuse cervicomental angle, but
      good-quality skin, there may be no need to perform skin resection. In these
      patients who are candidates for nonexcisional cervicoplasty, we routinely place a
      neck suspension suture. Patients with poor skin quality or excessive skin on the
      neck and jawline will require an excisional cervicoplasty or cervicofacial
      rhytidectomy. We have obtained consistently good results using this comprehensive
      approach.

PMID- 11598820
TI  - Targeted solutions in submentoplasty.
AB  - Obtaining superior aesthetic results in the cervical-mental region requires
      accurately diagnosing the underlying anatomic abnormality. We have designed a
      comprehensive classification scheme based on diagnostic and surgical methods from
      a facial plastic surgical practice with 30 years of experience. Patients can be
      classified into the suggested system to determine the optimal rejuvenation
      technique.

PMID- 11598821
TI  - Osteochondroma as a causal agent in popliteal artery pseudoaneurysms: case report
      and literature review.
AB  - Osteochondromas are an infrequent, but significant, source of vascular injuries.
      Popliteal artery pseudoaneurysms are the most common sequelae, with a complex
      interplay of anatomic and developmental factors accounting for their prevalence.
      The authors present a case report, detailed discussion, and literature review of
      pseudoaneurysm formation in the popliteal artery.

PMID- 11598822
TI  - Continuous cervical epidural anesthesia in hand surgery.
AB  - Regional anesthesia, with its known benefits such as increased blood flow,
      reduced cost, and security, is a method of choice for hand surgery. Recently, the
      authors have switched from axillary block to continuous cervical epidural
      anesthesia, which has several advantages such as low cost, a pain-free
      postoperative period, better control of tourniquet pain, and the avoidance of a
      motor block so that early active motion is possible. Continuous cervical epidural
      anesthesia is a safe and reliable method, providing a sensory block with an
      infusion rate of 4 ml/hr ultracaine (articaine 2 percent), and a motor block when
      the dosage is increased to 8 ml/hr ultracaine (articaine 2 percent).
      Postoperatively, only 4 ml/hr ultracaine (articaine 2 percent) is sufficient to
      provide a sensory block. The method provides both good perfusion and a lower
      local anesthetic drug dosage than axillary block.

PMID- 11598823
TI  - Ipsilateral pedicle vascularized fibula grafts for reconstruction of tibial
      defects and non-unions.
AB  - Between October 1983 and August 1998, 31 patients with non-union or bone defect
      of the tibia have undergone 32 vascularized fibula transfers to reconstruct lower
      legs. Of these 32 vascularized fibula transfers, there were 19 pedicle transfers
      from the ipsilateral leg. There were 17 males and two females. The average
      patient age was 53 (21 to 84) years old. All patients achieved good bone
      reconstruction. All patients are currently able to walk without a brace, except
      for one. As to major complications, three of these 19 had delayed union, with
      only one postoperative fracture. In the cases with delayed union or fractured
      grafted fibulas, the periods to walking without a brace were longer than in the
      cases without such major complications. From the results, the ipsilateral pedicle
      vascularized fibula graft appears to be a useful option for reconstruction of
      tibial defects.

PMID- 11598824
TI  - Combining free vascularized fibula graft and the Ilizarov external fixator:
      recent approaches to congenital pseudarthrosis of the tibia.
AB  - The present study compares a recent approach for congenital pseudarthrosis of the
      tibia, combining a free vascularized fibula graft and an Ilizarov external
      fixator. Between 1984 and 1993, seven vascularized fibula grafts were performed.
      In the first six cases, casts or unilateral external fixators were applied, and
      five of these cases were complicated by fractures of the graft, necessitating
      secondary procedures or long-term immobilization. The mean follow-up was 12.1
      years. Five patients can now walk unassisted, and one uses a brace only outdoors.
      On average, a brace was required for 18 months. In the recent Ilizarov external
      fixator case, the fixator was removed after 4 months and a brace was unnecessary
      at 10 months. There was no leg-length discrepancy, severe ankle deformity, or
      fracture of the grafted fibula 7 years postoperatively. Combining a free
      vascularized fibula graft with an Ilizarov external fixator is recommended for
      this condition.

PMID- 11598825
TI  - Combination of anti-ICAM-1 and anti-LFA-1 monoclonal antibody therapy prolongs
      allograft survival in rat hind-limb transplants.
AB  - Immunosuppressive effects of monoclonal antibodies against adhesion molecules
      were validated in solid organ transplants. There have been only a few reports on
      the effect of these antibodies on limb transplantation. In this study, the
      authors investigated the effects of anti-ICAM-1 and anti-LFA-1 therapy in the rat
      hind-limb-cremaster transplantation model. Twenty transplantations were performed
      across a major histocompatibility barrier between Lewis Brown Norway (LBN, RT
      1(l+n)) and Lewis (LEW, RT-1(l)) rats in four experimental groups of five animals
      each. Group 1 animals received only vehicle solution; Groups 2 and 3 received
      monoclonal antibodies against ICAM-1 and LFA-1, respectively; Group 4 received a
      combination dose. Treatments were continued for 7 days. Clinical signs of
      rejection were noted daily, and correlated with in vivo microcirculatory
      measurements. The activation of adhering leukocytes was significantly lower in
      rats treated with anti-ICAM-1, anti-LFA-1, and combination than in controls (p <
      0.05). Transmigrating leukocytes were also reduced in antibody-treated groups,
      when compared to the control group (p < 0.05). The mean number of rolling
      lymphocytes was significantly reduced only in the combination group (p < 0.05).
      Endothelial edema index, a measure of endothelial swelling, was lowest in the
      combination group (p < 0.05). The first clinical signs of rejection were noted
      between the 5(th) and 9(th) days in the control group, on the 9(th) day in the
      anti-ICAM-1 or anti-LFA-1 groups, and on the 13(th) day with combination therapy.
      Monoclonal antibodies against LFA-1 or ICAM-1 alone inhibit the activation of
      leukocytes at the microcirculatory level but do not prolong graft survival.
      However, the combination of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies
      significantly prolonged allograft survival in this composite tissue
      transplantation model.

PMID- 11598826
TI  - Location and length of arteriovenous fistulas around axial-pattern skin-flap
      pedicles.
AB  - The importance of the location of a surgically-created arteriovenous fistula
      around the pedicle (both distal and proximal) on the viability of rat skin flaps
      was investigated. The animals were randomly divided into four groups. Group 1
      included bilateral standard island groin flaps. The right side flap was used as a
      control. On the left side, after elevation of the flap, an X-type arteriovenous
      fistula greater than 1 mm (up to 2 mm) in length was created distal to the
      pedicle, and just before the bifurcation of the common femoral vessels. In Group
      2, the flap was an axial-pattern medially-based peninsular flap, including the
      same vessels. In this group also, two flaps were elevated bilaterally, and the
      right side was used as a control; on the left side, an X-type arteriovenous
      fistula the same length as in Group 1 was also created distal to the pedicle. In
      both groups, all other branches of the common femoral vessels were kept intact.
      In a second part of the study, two other animal groups were used to clarify the
      importance of the length of the arteriovenous fistula on the viability of skin
      flaps. In Group 3, the model was the same as in Group 1, but the fistula was 1 mm
      in length. In Group 4, the length of the fistula was 1 mm, and its location was
      on the common femoral vessels proximal to the pedicle, using the same flap model.
      Flow values were measured repeatedly using a laser Doppler flowmeter.
      Histopathologic studies were also done. There are three important points arising
      from these studies. 1). The location of an X-type arteriovenous fistula around an
      island skin flap pedicle seems to be more important than diameter. An
      arteriovenous fistula proximal to the pedicle is more hazardous than an
      arteriovenous fistula distal to the pedicle, regarding island skin-flap
      viability. 2). However, the length of the fistula is also important, and an
      arteriovenous fistula distal to the pedicle, with a sufficiently long length, is
      not devoid of harmful effects. It is also clear that the larger the fistula, the
      greater the systemic effects. 3). An island skin flap with an arteriovenous
      fistula distal to its pedicle might be a useful model to study the relationship
      between skin-flap viability and edema formation.

PMID- 11598827
TI  - Standardizing nerve crushes with a non-serrated clamp.
AB  - Standardized experimental nerve crush attempts should include the number,
      duration, and intensity (amount of pressure) of crushes. The authors have
      developed a new crushing device, a clamp with which predetermined forces can be
      applied to nerves. This allows the exertion of different, standardized forces to
      crush a nerve within a scale that produces second-degree injuries. The main
      advantages of the clamp are that it is small, although very robust, is purely
      mechanical, and is easy to handle. The jaws of the clamp are not serrated, so
      that pressure on the nerve is uniformly transmitted. To avoid unintended nerve
      damage, the edges of the jaws are smoothly rounded off. The closure of the clamp
      is mechanized by a spring. As the spring is exchangeable, any number of different
      preloads are available. The force can be varied, according to different
      requirements, and is applicable to variantly thick nerves in any experimental
      animal, thus enhancing standardization, and making cross-over comparisons of
      experimental study results possible.

PMID- 11598828
TI  - Circulatory changes after prolonged ischemia in the epigastric flap.
AB  - The circulation system seems to have early encounters with pathophysiologic
      processes during ischemia and reperfusion, such as overproduction of oxygen
      radicals, nitric oxide depletion, and leukocyte plugging. The aim of this study
      was to determine the superficial perfusion and vessel distribution of the
      epigastric flap with a laser Doppler Imaging (LDI) system during
      ischemia/reperfusion, and to observe the clinical outcomes 7 days after
      reperfusion in a separate set of animals. An epigastric flap from male Sprague
      Dawley rats (320 to 380 g) was used to assess perfusion in sham animals (n=6) or
      in 12 hr-ischemia animals (12 hr of ischemia and 3 hr of reperfusion, n = 10)
      with the LDI system. In a separate experiment, flap size, flap failure index, and
      histologic sections of the flap from sham animals (n=6) and 12-hr ischemia
      animals (n=6) were evaluated 7 days after reperfusion. Evaluation of the vessel
      distribution demonstrated a diffuse picture of flap perfusion after clamp
      release. Moreover, in the distal portion of the flap, circulation stopped
      immediately, resulting in a significantly decreased perfusion in the 12-hr
      ischemia animals during reperfusion, when compared with pre-surgical values (100
      percent) or sham animals (77 +/- 26.5 vs. 108 +/- 9.6 percent PU). On day 7, the
      flaps of animals after ischemia and reperfusion showed significant shrinkage, an
      increase in flap failure index, as well as necrosis, edema, and leukocyte
      infiltration. Based on the findings, the authors propose that, after prolonged
      ischemia, the circulation becomes diffuse, and "no-reflow" occurs in the distal
      portions of the myocutaneous flap during reperfusion. Perfused areas, assessed
      with the LDI early during reperfusion, might still become necrotic after several
      days. In the authors' flap model, edema formation and leukocyte infiltration seem
      to be related more to ischemia reperfusion damage than to thrombus formation.

PMID- 11598830
TI  - Outbreak of human parainfluenza virus 3 infections in a hematopoietic stem cell
      transplant population.
AB  - Clinical manifestations and epidemiological features are described for a cluster
      of 12 cases of human parainfluenza virus 3 (HPIV3) infection that occurred among
      64 allogeneic hematopoietic stem cell transplant (SCT) recipients in an 11-week
      period during spring 2000. Upper respiratory symptoms predominated. Pneumonia
      occurred in 3 patients and was a contributing factor in the death of 1 patient.
      Exposure histories and molecular analysis of HPIV3 isolates suggested that both
      community acquired and nosocomially transmitted infections occurred during this
      outbreak. A chain of transmission within the outpatient clinic appeared to have
      occurred in 4 outpatients and to have extended to 2 hospitalized patients.
      Molecular epidemiology was useful in discerning routes of transmission in this
      outbreak.

PMID- 11598829
TI  - A genomewide scan for type 1-diabetes susceptibility in Scandinavian families:
      identification of new loci with evidence of interactions.
AB  - Type 1 diabetes mellitus (TIDM) has a multifactorial etiology, with major genetic
      susceptibility determinants located in the HLA and insulin-gene (INS) regions.
      Linkage data implicating other disease-susceptibility loci are conflicting. This
      is likely due to (1) the limited power for detection of contributions of
      additional susceptibility loci, given the limited number of informative families
      available for study, (2) factors such as genetic heterogeneity between
      populations, and (3) potential gene-gene and gene-environment interactions. To
      circumvent some of these problems, we have conducted a genomewide linkage
      analysis for T1DM-susceptibility loci in 408 multiplex families from Scandinavia,
      a population expected to be homogeneous for genetic and environmental factors. In
      addition to verifying the HLA and INS susceptibility loci, the study provides
      confirmation of IDDM15 on chromosome 6q21. Suggestive evidence of additional
      susceptibility loci was found on chromosomes 2p, 5q, and 16p. For some loci, the
      support for linkage increased substantially when families were stratified on the
      basis of HLA or INS genotypes, with statistically significant heterogeneity
      between the stratified subgroups. Our data support both the existence of non-HLA
      genes of significance for T1DM and interaction between HLA and non-HLA loci in
      the determination of the T1DM phenotype.

PMID- 11598831
TI  - Antibody-dependent enhancement of coxsackievirus B4 infectivity of human
      peripheral blood mononuclear cells results in increased interferon-alpha
      synthesis.
AB  - IgG devoid of neutralizing activity and isolated from donor plasma by
      chromatography formed immune complexes with coxsackievirus B4 (CVB4) and
      significantly increased the infection of peripheral blood mononuclear cells with
      CVB4. The major host cells for CVB4 infection enhanced with IgG are monocytic
      CD14+ cells. The roles of CVB and adenovirus receptor and Fcgamma receptor II and
      III have been shown. Increased viral replication and the release of infectious
      particles were demonstrated when interferon (IFN)-alpha produced by infected
      cells was first neutralized by use of antibodies. The CVB4 IgG-induced synthesis
      of IFN-alpha by monocytes reflected entry and uncoating of CVB4 but not of viral
      replication and required the presence of CVB4 RNA inside the cells. Thus, CVB4
      can infect monocytes by an antibody-dependent mechanism through interactions
      between the virus, antiviral antibodies, and specific receptors that result in
      IFN-alpha production.

PMID- 11598832
TI  - Serum of cytomegalovirus-infected mice induces monocyte chemoattractant protein-1
      expression by endothelial cells.
AB  - Inflammation plays a central role in atherogenesis. It was hypothesized that
      infection of apolipoprotein E-deficient mice with murine cytomegalovirus (MCMV)
      increases serum levels of proinflammatory cytokines, which may induce
      "proatherosclerotic" changes in endothelial cells (ECs). Serum samples were
      collected from uninfected and infected mice. ELISA was used to determine cytokine
      serum levels and monocyte chemoattractant protein-1 (MCP-1) levels in the
      supernatant of mouse ECs incubated with serum-containing medium. Serum samples
      from infected mice induced MCP-1 expression by ECs. These serum samples contain
      interferon (IFN)-gamma, whereas IFN-gamma was undetectable in serum samples from
      uninfected mice. Preincubating infected mouse serum with anti-IFN-gamma
      monoclonal antibody significantly decreased serum-induced EC expression of MCP-1.
      Thus, MCMV infection increases IFN-gamma serum levels, such serum can induce MCP
      1 in ECs, and the serum-induced MCP-1 expression is due, at least in part, to IFN
      gamma. If these changes in EC function also occur in vivo in response to
      infection, they could exacerbate atherogenesis.

PMID- 11598833
TI  - Human T lymphotropic virus type 1 infection influences hepatitis C virus
      clearance.
AB  - To explore the effect of human T lymphotropic virus type 1 (HTLV-1) infection on
      hepatitis C virus (HCV) infection, a survey for these viral infections was
      conducted that involved 2280 residents in an area in which HTLV-1 and HCV are
      endemic. The response of patients with HCV and HTLV-1 to interferon (IFN)-alpha
      treatment was also assessed. Antibody to HCV was detected in 13.8% of the
      residents tested, and antibody to HTLV-1 was detected in 15.4%. The prevalence of
      HCV RNA was significantly higher among residents who had antibodies to both HCV
      and HTLV-1 than in those who had antibodies to HCV only (P<.05). Sustained
      elimination of HCV RNA by IFN was significantly more frequent among patients with
      HCV alone than among those with HCV and HTLV-1. By logistic regression analysis,
      HTLV-1 infection was associated with nonresponse to IFN treatment. Thus, HTLV-1
      infection affects the clearance, both natural and in association with IFN
      treatment, of HCV.

PMID- 11598834
TI  - Antiretroviral resistance mutations among pregnant human immunodeficiency virus
      type 1-infected women and their newborns in the United States: vertical
      transmission and clades.
AB  - To assess the impact of antiretroviral resistance on perinatal transmission
      prevention efforts, human immunodeficiency virus type 1 (HIV-1) genotypic
      resistance testing was done for 220 HIV-1-infected, zidovudine (AZT)-exposed
      pregnant women and 24 of their infected infants. The women were prospectively
      enrolled in 4 US cities in 1991-1997. Phylogenetic and sequencing analyses
      revealed 5 women with non-clade B infections traced to western African origins.
      AZT-associated mutations were detected in 17.3% of pregnant women, whereas
      genotypic resistance to nonnucleoside reverse-transcriptase inhibitors and
      protease inhibitors was infrequent. No significant association was detected
      between perinatal transmission and the presence of either AZT or nucleoside
      reverse-transcriptase inhibitor resistance-associated mutations. AZT resistance
      mutations were detected in 2 (8.3%) neonatal samples, but the mutation pattern
      was not identical to the mother's. Although no effect of viral resistance on
      mother-infant transmission was demonstrated, the advent of more-potent drug
      classes and the potential for the rapid emergence of resistance warrant
      prospective surveillance.

PMID- 11598835
TI  - Anatomically compartmentalized human immunodeficiency virus replication in HLA
      DR+ cells and CD14+ macrophages at the site of pleural tuberculosis coinfection.
AB  - This study examined the impact of the host inflammatory microenvironment
      associated with localized tuberculosis (TB) on human immunodeficiency virus type
      1 (HIV-1) replication within lymphocytes and macrophages in vivo. Paired plasma
      and pleural fluid samples from HIV-1-infected individuals with pleural TB (n=9)
      were analyzed. Detection of host proteins incorporated into the HIV-1 envelope by
      immunomagnetic capture analysis provided insight into the phenotype of cells
      supporting HIV-1 replication. The results indicated that the 4.0-fold greater
      median HIV-1 load in pleural fluid, compared with median load in plasma (P<.01),
      was derived in part from viral replication within HLA-DR+ cells, CD26+
      lymphocytes, and, importantly, CD14+ macrophages. Greatly increased local
      concentrations of proinflammatory cytokines and immune activation markers in the
      pleural space correlated with the virologic findings. In summary, HIV-1
      replication was increased at sites of Mycobacterium tuberculosis coinfection
      within activated cells, including lymphocytes and CD14+ macrophages.

PMID- 11598836
TI  - Acute ethanol intoxication suppresses lung chemokine production following
      infection with Streptococcus pneumoniae.
AB  - Alcohol intoxication impairs neutrophil function and increases host
      susceptibility to Streptococcus pneumoniae. In a rat model of pneumonia, the
      effects of acute intoxication were monitored for lung chemokine responses,
      neutrophil recruitment, and bactericidal activity. Alcohol delayed lung
      neutrophil recruitment, increased bacterial burden, and decreased survival.
      Before neutrophil recruitment, bronchoalveolar lavage (BAL) macrophage
      inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant
      (CINC) were decreased by alcohol. This alcohol-induced effect was reversed at 6
      h, when there were large numbers of neutrophils in control BAL fluid, compared
      with the alcohol-treated group. Cyclophosphamide-induced neutropenia decreased
      neutrophil recruitment, minimizing the effects of recruited neutrophils on
      chemokine levels, and extended the alcohol-induced chemokine suppression. MIP-2
      and CINC mRNA contents also were suppressed by alcohol 4 and 6 h after infection.
      Thus, alcohol suppresses lung chemokine activity in response to S. pneumoniae,
      which is associated with delayed neutrophil delivery, elevated bacterial burden,
      and increased mortality.

PMID- 11598837
TI  - Characteristics of surfactant protein A and D binding to lipoteichoic acid and
      peptidoglycan, 2 major cell wall components of gram-positive bacteria.
AB  - Infection with gram-positive bacteria is a major cause of pneumonia. Surfactant
      proteins A (SP-A) and D (SP-D) are thought to play an important role in the
      innate immunity of the lung. Both proteins can bind to gram-positive bacteria.
      Until now, it was not known with which surface component(s) of gram-positive
      bacteria SP-A and SP-D interact. Lipoteichoic acid (LTA) and peptidoglycan (PepG)
      are components of the cell wall of gram-positive bacteria. By use of a solid
      phase-based binding assay, LTA of Bacillus subtilis was shown to be bound by SP-D
      but not by SP-A. Unmodified PepG of Staphylococcus aureus was bound by SP-D. SP-D
      binding to both LTA and PepG was calcium dependent and carbohydrate inhibitable.
      These results indicate that SP-D interacts with gram-positive bacteria via
      binding to the cell wall components LTA and PepG and that the carbohydrate
      recognition domain is responsible for this binding.

PMID- 11598838
TI  - Mannose-binding lectin regulates the inflammatory response of human professional
      phagocytes to Neisseria meningitidis serogroup B.
AB  - The influence of the innate immune protein mannose-binding lectin (MBL) on the
      response of human phagocytes to Neisseria meningitidis was investigated. MBL
      increased the association of killed meningococci with neutrophils, monocytes, and
      macrophages by increasing the proportion of cells that recognized bacteria. MBL
      down-regulated the normal change in expression of the leukocyte adhesion
      molecules CD11b and CD62L. In an ex vivo model, the addition of MBL to the blood
      of MBL-deficient donors influenced the production of monocyte-derived
      inflammatory cytokines. The addition of high concentrations of MBL (>6 microg/mL)
      profoundly decreased the production of interleukin (IL)-6, IL-1beta, and tumor
      necrosis factor-alpha by monocytes in response to meningococci, whereas lower
      concentrations enhanced the production of IL-6 and IL-1beta. These results
      suggest that MBL not only is involved in complement activation but also is a
      potent regulator of inflammatory pathways and, as such, may affect the severity
      of meningococcal disease.

PMID- 11598839
TI  - Carriage of antibiotic-resistant fecal bacteria in Nepal reflects proximity to
      Kathmandu.
AB  - Within Nepal, geographic, social, and economic barriers greatly limit access to
      allopathic health care. The country therefore offered the opportunity to evaluate
      the effect of antibiotic accessibility (as measured by allopathic medicine
      consumption) on antibiotic resistance in the normal intestinal flora. The aerobic
      gram-negative fecal flora of 33-34 healthy adults from each of 3 villages with
      different access to health care facilities in Kathmandu were examined for
      antibiotic susceptibility. The frequency of antibiotic resistance decreased
      significantly with increasing distance from Kathmandu and decreasing population
      density but did not reflect contact with health care providers or individual
      medicine consumption. The findings suggest that an individual's overall exposure
      to antibiotics and antibiotic-resistant bacteria (resulting from close proximity
      to other community members and to sources of accessible allopathic health care,
      such as in the vicinity of Kathmandu), has an equal or greater impact on an
      individual's carriage of antibiotic-resistant bacteria than does direct
      consumption of antibiotics.

PMID- 11598840
TI  - Adherence and invasion studies of Candida albicans strains, using in vitro models
      of esophageal candidiasis.
AB  - The adherence of clinical and commensal isolates and reference collection strains
      of Candida albicans to a human esophageal cell monolayer (HET1-A) and
      reconstituted human esophageal tissue was compared. Isolates from patients with a
      severe form of esophageal candidiasis or candidemia adhered to HET1-A cells to a
      significantly greater extent than did isolates from patients with mild esophageal
      candidiasis or commensal and reference collection strains. In addition, C.
      albicans strain SSK21, which lacks the ssk1 response regulator gene of a 2
      component signal transduction pathway, adhered less readily to the HET1-A cells
      than did parental cells or a gene-reconstituted strain. In a reconstituted
      esophageal tissue model, all clinical strains but not commensal or reference
      collection strains penetrated the epithelium, albeit at different rates. Hyphal
      formation following yeast cell adherence to the esophageal tissue was a
      requirement for invasion. Scanning electron microscopy was also used to confirm
      the colonization of the esophageal tissues by various strains. These studies
      indicate that both the HET1-A and the reconstituted esophageal tissue models can
      be used as in vitro targets to evaluate the adherence phenotype and invasiveness
      of C. albicans strains.

PMID- 11598841
TI  - Schistosoma haematobium-induced urinary tract morbidity correlates with increased
      tumor necrosis factor-alpha and diminished interleukin-10 production.
AB  - This study examined the hypothesis that the nature of the host cellular immune
      response to schistosome ova is a risk factor for urinary tract morbidity in areas
      in which Schistosoma haematobium is endemic. S. haematobium-infected children and
      adolescents with bladder pathology assessed by ultrasonography had 54-fold
      greater tumor necrosis factor (TNF)-alpha production and a 120-fold greater ratio
      of TNF-alpha to interleukin (IL)-10 release by peripheral blood mononuclear cells
      in response to egg antigens, in comparison with control children and adolescents
      matched by age, sex, and infection severity. Mycobacterial antigens also
      stimulated 7-fold more TNF-alpha among subjects with bladder morbidity than in
      control subjects, which suggests an innate predisposition to enhanced TNF-alpha
      production. Levels of egg antigen-induced IL-4 and -5 and interferon-gamma were
      equivalent in subjects with and without bladder pathology. Thus, children and
      adolescents predisposed to increased TNF-alpha production to S. haematobium
      infection are more likely to develop an exaggerated granulomatous response to ova
      trapped in the bladder wall, with associated urinary tract pathology.

PMID- 11598842
TI  - Neutralization of human papillomavirus type 11 (HPV-11) by serum from women
      vaccinated with yeast-derived HPV-11 L1 virus-like particles: correlation with
      competitive radioimmunoassay titer.
AB  - Neutralization of human papillomavirus type 11 (HPV-11) has been demonstrated
      using serum and cervical secretions from primates vaccinated with virus-like
      particles (VLPs). Theoretically, neutralizing antibodies could protect women from
      HPV infection. The immunogenicity of a yeast-derived HPV-11 L1 VLP vaccine was
      tested in women. Serum specimens were evaluated for HPV-11 titer by competitive
      radioimmunoassay (cRIA) and for neutralization by use of the athymic mouse
      xenograft system. Analysis of serum from 104 subjects showed a dose response in
      HPV-11 cRIA titers and neutralization. Overall, 68 (82.9%) of 82 postimmunization
      serum specimens from VLP recipients were 100% neutralizing when used in the assay
      at a 1:50 dilution. Of 69 serum specimens, 63 (91.3%) with cRIA titers >200
      milliMerck units per milliliter were neutralizing. Immunization with HPV VLPs
      elicits a vigorous serum immune response in a high percentage of women. The HPV
      11 cRIA titer appears to be a surrogate marker for neutralization.

PMID- 11598843
TI  - Variation of human immunodeficiency virus type 1 viral RNA levels in the female
      genital tract: implications for applying measurements to individual women.
AB  - The short-term detection and variability of human immunodeficiency virus type 1
      (HIV-1) RNA level was assessed in the blood plasma and genital tracts of 55 HIV-1
      infected women. Specimens were collected weekly for 8 weeks from the endocervical
      canal with wicks and cytobrushes and from the ectocervix and vagina with
      cervicovaginal lavage. In all, 48 women (87.3%) had detectable genital tract HIV
      1 RNA at > or =1 collection times. HIV-1 RNA levels varied least in specimens
      from endocervical canal wick and most in cervicovaginal lavage samples. The
      within-subject variation for genital-tract virus level was greater than that for
      blood. Overall, the odds for viral RNA detection in the genital tract
      approximately tripled for each 10-fold increase in plasma viral RNA concentration
      (P<.001) or with concomitant genital tract infection (P=.003). Endocervical canal
      wicks should be considered as an adjunct to cervicovaginal lavage, to improve the
      sensitivity and precision of HIV-1 RNA detection.

PMID- 11598844
TI  - The immunomodulatory effects of thalidomide on human immunodeficiency virus
      infected children.
AB  - The safety and immune effects of low-dose thalidomide treatment (3 mg/kg/day for
      28 days) were evaluated in a study involving 8 South African human
      immunodeficiency virus (HIV)-infected children. The children were 7-69 months old
      and in disease stages A1-C3. Thalidomide therapy did not affect virus load, even
      though none of the children was receiving antiretroviral therapy. Thalidomide
      stimulated CD8+ T cells in peripheral blood, which increased expression of the
      activation markers CD38 and human leukocyte antigen DR and of the memory cell
      marker CD45RO. The frequency of HIV gag-specific CD8+ T cells in peripheral blood
      increased in 3 of 4 children who were evaluated during treatment with
      thalidomide. Clinical adverse events were mild. In this study, thalidomide was
      found to be safe and well tolerated and caused significant immunomodulation at a
      low dose. This is the first report describing use of an oral drug that may
      enhance HIV-specific CD8+ T cell function in HIV-infected children.

PMID- 11598845
TI  - Switching to nevirapine decreases insulin levels but does not improve
      subcutaneous adipocyte apoptosis in patients with highly active antiretroviral
      therapy-associated lipodystrophy.
AB  - Subcutaneous adipocyte apoptosis occurs in lipotrophic areas of patients with
      highly active antiretroviral therapy (HAART)-associated lipodystrophy. Fourteen
      patients with HAART-associated lipodystrophy had 2 subcutaneous biopsies for
      evidence of adipocyte apoptosis, the second after a randomized change to
      nevirapine (n=8) or after remaining on a regimen of indinavir-based HAART (n=6).
      Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP
      digoxigenin nick end-labeling method. Patients who were switched to nevirapine
      had a significant decrease in insulinemia and a significant increase in the
      glucose:insulin ratio. Overall, subcutaneous adipocyte apoptosis increased in 3
      patients who were switched to nevirapine and in 3 who continued to receive
      indinavir but decreased in 2 patients switched to nevirapine and another 2 who
      continued to receive indinavir. Subcutaneous adipocyte apoptosis continues to
      occur in lipotrophic areas of patients with HAART-associated lipodystrophy
      despite switching from indinavir to nevirapine, suggesting that such a strategy
      will be useless for reversal of lipoatrophy.

PMID- 11598846
TI  - Lack of association of hepatitis C virus load and genotype with risk of end-stage
      liver disease in patients with human immunodeficiency virus coinfection.
AB  - In hepatitis C virus (HCV) infection, virus load and the risk for HCV-related end
      stage liver disease (ESLD) are increased among persons with human
      immunodeficiency virus (HIV) coinfection. To clarify these relationships, 42
      hemophilic patients who developed ESLD and random samples from 164 hemophilic
      patients with HCV infection alone and 146 with HCV-HIV coinfection were tested
      for HCV load and genotype. HCV genotype was unrelated to HIV and age. In
      contrast, HCV load was higher with older age (P(trend)=.0001) and with HIV
      coinfection (6.2 vs. 5.9 log(10) genome equivalents/mL, P=.0001). During 16 years
      of follow-up of dually infected patients, ESLD risk was unrelated to HCV load
      overall (P(trend)=.64) or separately to HCV genotype 1 and genotypes 2 or 3
      (P(trend)> or =.70). Irrespective of virus load, incidence of ESLD was marginally
      increased 2-fold (95% confidence interval, 0.8-5.6) with HCV genotype 1.
      Understanding the discordance between HCV load and ESLD, despite HIV's link to
      each of these, may help clarify the pathogenesis of HCV-related disease.

PMID- 11598847
TI  - Multilocus sequence typing of Streptococcus pneumoniae clones with unusual drug
      resistance patterns: genetic backgrounds and relatedness to other epidemic
      clones.
AB  - Six drug-resistant Streptococcus pneumoniae clones were previously identified
      from day care centers in Portugal, primarily on the basis of common pulsed-field
      gel electrophoresis (PFGE) patterns. These clones were susceptible to penicillin
      or had only very low-level resistance to it (most MICs, < or =0.25 microg/mL) and
      accounted for a large proportion (35%) of all drug-resistant pneumococci
      colonizing the nasopharynx of healthy children attending day care. Five of the 6
      clones were identified among pneumococcal clinical isolates collected in other
      countries. In this study, we applied multilocus sequence typing (MLST) to
      describe the genetic background of these clones. MLST confirmed previous findings
      obtained by PFGE and allowed for the extension of the international clonal
      relationships by showing that each of the 6 clones was internationally
      disseminated and was able to cause pneumococcal disease.

PMID- 11598848
TI  - Avidity and subclasses of IgG after immunization of infants with an 11-valent
      pneumococcal conjugate vaccine with or without aluminum adjuvant.
AB  - Finnish and Israeli infants received an 11-valent mixed-carrier pneumococcal
      conjugate vaccine with or without aluminum adjuvant at 2, 4, 6, and 12 months of
      age. The relative avidity of serotype 1-, 5-, 6B-, 14-, 19F-, and 23F-specific
      IgG antibodies in serum obtained at 7, 12, and 13 months of age was measured by
      EIA, using thiocyanate as a chaotropic agent. For all serotypes, except 14,
      avidity increased between the ages of 7 and 12 months. After boosting at 12
      months, avidity further increased for all serotypes. The adjuvant improved
      antibody avidity against serotype 5. The IgG antibodies produced were mainly IgG1
      subclass, although some infants also produced IgG2 after boosting. In conclusion,
      the immunization of infants with this 11-valent pneumococcal conjugate vaccine
      increased avidity of IgG, suggesting successful immunologic priming.

PMID- 11598849
TI  - Features of Chlamydia trachomatis and Neisseria gonorrhoeae infection in male
      Army recruits.
AB  - Non-health care-seeking male United States Army recruits were tested for
      Chlamydia trachomatis (n=2245) and Neisseria gonorrhoeae (n=884), using a urine
      ligase chain reaction test to determine prevalence and potential risk factors for
      infection. The prevalence of chlamydial infection was 5.3%. Black race, a new sex
      partner, a history of trichomonas, and the presence of symptoms were associated
      with chlamydial infection. The prevalence of N. gonorrhoeae infection was 0.6%.
      Only a reported history of or positive test for C. trachomatis was associated
      with gonorrheal infection. Of those testing positive for chlamydia, 14% reported
      symptoms versus 40% of those with gonorrhea. Younger age was not a predictor of
      either infection, as has been shown for women. A substantial number of male army
      recruits are infected with C. trachomatis, but few are infected with N.
      gonorrhoeae. Screening on the basis of symptoms alone would miss the majority of
      both infections.

PMID- 11598850
TI  - Dendritic cells pulsed with Coccidioides immitis lysate induce antigen-specific
      naive T cell activation.
AB  - Coccidioidomycosis, an infection endemic to the southwestern United States, is
      caused by the fungus Coccidioides immitis. Coccidioidal infection is overcome by
      the development of cell-mediated immunity. This study evaluated the role of
      dendritic cells (DCs) in the initiation of coccidioidal immunity in nonimmune
      individuals. It was demonstrated that DCs pulsed with the coccidioidal antigen
      preparation, toluene spherule lysate (TSL), induce DC maturation, autologous
      lymphocyte proliferation, and antigen-specific lymphocyte responses from
      nonimmune donors. Furthermore, TSL-primed lymphocytes secreted interferon-gamma
      after restimulation with TSL or antigen 2/proline-rich antigen, a subcomponent of
      TSL, but they did not do so when restimulated with ovalbumin or unpulsed DCs. The
      results demonstrate that DCs generated from individuals not exposed to C. immitis
      can specifically prime lymphocytes for coccidioidal antigens and that the
      response generated by the lymphocytes is characteristic of a cellular immune
      response.

PMID- 11598851
TI  - T cell apoptosis in human immunodeficiency virus type 1 infection: is there a
      relationship between CD95 sensitivity and thymic regeneration of CD4+ T cells?

PMID- 11598853
TI  - Primary liposarcoma of the orbit: a clinicopathologic study of seven cases.
AB  - Liposarcoma, the most common soft tissue sarcoma in adults, will rarely involve
      the orbit, either primarily or as a metastasis. We describe seven primary orbital
      liposarcomas, representing the largest documented series of primary orbital
      liposarcoma to date. Affected patients were three males and four females ranging
      in age from 28 to 69 years (median, 51 years). Five patients presented with
      painless proptosis, one patient had painful proptosis, and no details of
      presenting symptoms are available in one case. The site distribution was
      retrobulbar (3 cases), lateral orbital wall (2 cases), medial wall (1 case), and
      unspecified (1 case). Radiologic impression included hemangioma, lipoma, and an
      inflammatory process. Lesional size ranged from 2.8 to 4 cm. Five liposarcomas
      were purely well-differentiated, one was dedifferentiated, and one was
      pleomorphic in type. The well-differentiated cases comprised the following
      subtypes: spindle cell (2 cases), adipocytic (2 cases), and combined
      adipocytic/sclerosing/inflammatory (1 case). Five patients underwent orbital
      exenteration (one followed by radiation) and two had marginal/partial excision of
      their tumors. Follow-up was available for five patients, ranging from 13 to 204
      months (median 65 months). Four patients showed no evidence of recurrence,
      including the patient with pleomorphic liposarcoma who had a long, disease-free
      survival (65 months) following marginal excision. One patient has had multiple
      recurrences following initial partial excision. One patient died of an unrelated
      cause with no clinical evidence of recurrence. Despite the difficulty in
      obtaining wide surgical margins, the small tumor size at presentation and the
      apparent predominance of the well-differentiated type means that the prognosis
      for orbital liposarcoma is generally good. In view of the various morphologic
      patterns that may occur, liposarcoma should be considered in the differential
      diagnosis of any histologically unusual mesenchymal lesion in the orbit.

PMID- 11598854
TI  - Role of DNA ploidy analysis in endometrial adenocarcinoma.
AB  - Endometrial adenocarcinoma is the leading cause of malignancy of the female
      genital tract. Prognosis of this tumor, which has implications on patient
      management, is determined by evaluation of the stage of disease, architectural
      grade, nuclear grade, myometrial invasion, and peritoneal cytology. These
      parameters have inherent subjectivity and, therefore, the search for an objective
      reliable parameter to determine prognosis is required. DNA ploidy is under
      investigation as an objective and reproducible prognostic parameter. This study
      will evaluate the role of DNA ploidy and its relationship to the traditional
      parameters as predictors of prognosis in patients with endometrial carcinoma.
      Fifty-eight patients were evaluated by two observers for architectural grade
      according to the International Federation of Gynecology and Obstetrics
      classification, nuclear grade, and depth of myometrial invasion. DNA ploidy was
      evaluated using flow cytometer (FACscan, Becton Dickinson, San Jose, CA).
      Histologic parameters were than compared with DNA ploidy. Survival data were
      obtained from the tumor registry. Results of patient survival were compared with
      histologic parameters and DNA ploidy. Higher nuclear grade and aneuploidy
      correlated with poor survival rate (P <.05). Higher nuclear grade correlated with
      aneuploidy. The survival of patients with architectural grade 2 (moderately
      differentiated) endometrial adenocarcinoma is poorer if the tumor is aneuploid as
      compared with diploid as determined by flow cytometry. In conclusion, aneuploidy
      and nuclear grade correlates with poor patient survival. The poorer survival
      rates with aneuploid architectural grade 2 endometrial adenocarcinoma may have an
      impact on clinical management.

PMID- 11598855
TI  - Prognostic significance of percentage of bronchioloalveolar pattern in
      adenocarcinomas of the lung.
AB  - Bronchioloalveolar (BA) carcinoma of the lung is considered to have a better
      prognosis than that of common adenocarcinomas of the lung. However, a minor
      component of the BA pattern is common in many lung adenocarcinomas and the
      criteria for designating an adenocarcinoma as BA are not well defined. We
      assessed the clinicopathologic features of 238 cases of lung adenocarcinoma with
      a partial or predominant BA pattern. Tumors were classified as BA if more than
      75% of the tumor had a BA growth pattern. In other words, the tumor grew along
      pre-existing lung structures without invasion or destruction of parenchyma.
      Tumors with 50% to 75% BA pattern were considered mixed and tumors with less than
      50% BA pattern were designated as solid/acinar (S/A). Fixed, paraffin-embedded
      tissue sections of each neoplasm were also assessed using immunohistochemical
      methods with a panel of antibodies specific for p53, retinoblastoma protein, p16,
      cyclin D1, and cyclin E, and the results were correlated with clinical and
      pathologic parameters. Our results show that the 5-year survival rate of patients
      with BA and mixed tumors, 63% and 60%, respectively, was significantly better
      than that of patients with S/A tumors (P =.026). Patients with BA tumors were
      more frequently women (55.9%) compared with patients with mixed (48.3%) and S/A
      (43.8%) tumors. Bronchioloalveolar and mixed tumors were similarly associated
      with tobacco use, 88.2% and 85%, respectively; slightly less than S/A tumors
      (93.8%). Clinical and pathologic parameters did not correlate with
      immunohistochemical results. In conclusion, patients with BA or mixed tumors have
      similar 5-year survival, better than that of patients with S/A tumors, suggesting
      that adenocarcinomas can be designated as BA when at least 50% of the tumor has a
      BA pattern.

PMID- 11598856
TI  - Malignant teratoma of the thyroid with primitive neuroepithelial and mesenchymal
      sarcomatous components.
AB  - A 15-year-old black girl had a near total resection of a malignant thyroid
      teratoma with bilateral nodal involvement and mediastinal extension. A
      predominant neuroepithelial pattern had ependymal rosettes and mitoses, stained
      for neuron-specific enolase, neuron-specific B tubulin, and synaptophysin. A
      malignant spindle cell component stained for smooth-muscle actin, muscle actin,
      and to a lesser extent S-100. Loose myxoid tissue resembled primitive cartilage.
      Epithelial membrane antigen and cytokeratin identified epithelial foci.
      Chromogranin A, MIC2, glial fibrillary acidic protein, and thyroid stimulating
      hormone receptor stains were negative. There was focal anaplasia. DNA ploidy by
      laser scanning cytometry was 1.2. The tumor from the left and right thyroid lobes
      exhibited trisomy 8, the right also had hyperdiploid cell lines. She was treated
      with aggressive combination chemotherapy and radiation. Presently there is no
      residual disease 16 months after diagnosis. Malignant thyroid teratoma is an
      aggressive tumor, with 15 of 27 reported patients dying 2 weeks to 3 years after
      diagnosis. Survivors have been treated with total or subtotal resection,
      combination chemotherapy with agents effective in the treatment of germ cell
      tumors as well as sarcomas, and radiation for either recurrent or residual
      disease. The heterologous elements, lacking MIC2 staining and t(11;22), support
      the diagnosis of malignant teratoma rather than a neuroepithelial tumor. Trisomy
      8 is the first cytogenetic abnormality described in malignant thyroid teratoma.
      Therapy should be tailored to the management of all transformed histologies.

PMID- 11598857
TI  - Concurrent angiomyolipomas and renal cell carcinoma harboring metastatic foci of
      mammary carcinoma in the same kidney: an incidental autopsy finding in a patient
      with a follow-up of thirty years.
AB  - The synchronous occurrence of three different types of renal tumor in a patient
      is rare. We report a case of conventional (clear cell) renal cell carcinoma
      harboring metastatic foci of mammary carcinoma associated with two
      angiomyolipomas in the left kidney incidentally discovered at the autopsy. The
      patient was a 75-year-old woman, without the tuberous sclerosis complex, who had
      undergone left radical mastectomy and radiotherapy for an infiltrating duct
      carcinoma of breast 30 years before. This tumor was widely disseminated at
      autopsy, but the nontumorous renal parenchyma was free of metastases. To the best
      of our knowledge this combination of neoplasms has not been described before.
      This case shows the important role played by autopsy in the accurate
      investigation of interrelations among coexisting tumors.

PMID- 11598858
TI  - Primary epithelioid angiosarcoma of the adrenal gland.
AB  - Primary angiosarcomas of the adrenal gland are exceptionally rare vascular
      tumors. We report a case of a 63-year-old man with an epithelioid angiosarcoma of
      the left adrenal gland. Visualized on computed tomography as a nonhomogeneous
      round mass, the tumor measured 3 cm in diameter. Histology showed a vascular
      tumor composed of epithelioid cells with vesicular nuclei and prominent nucleoli
      that lined irregular vascular spaces and also formed solid areas and showed
      pleomorphism and rare mitotic activity. Immunohistochemical stain confirmed the
      diagnosis of epithelioid angiosarcoma. We report our findings and review
      previously described literature cases of this rare entity.

PMID- 11598859
TI  - Corticomedullary mixed tumor of the adrenal gland.
AB  - Corticomedullary mixed tumors of the adrenal gland are quite rare, with only five
      well-documented cases reported in the literature.(1-4) Herein, we report the
      light microscopic and immunohistochemical features of two cases of this rare
      tumor. Patient 1 is a 34-year-old woman who presented with hypertension, hair
      loss, and amenorrhea of 1-year duration. Patient 2 is a 52-year-old woman who
      presented with flank pain and what appeared to be a renal mass on arteriogram
      with no history of hypertension, Cushing's syndrome, or other endocrine
      abnormalities. At surgery, the tumor was noted to arise from the adrenal gland
      rather than the kidney and adrenalectomy was performed. In both cases, the
      surgically resected specimens consisted of a well-circumscribed, single adrenal
      mass surrounded by a rim of uninvolved adrenal cortical tissue. The tumors were
      composed of adrenal cortical cells intimately admixed with pheochromocytes.
      Immunohistochemical studies highlighted these two cellular components. The
      pheochromocytes were strongly reactive with chromogranin and the sustentacular
      cells with S-100 protein, whereas the adrenal cortical cells reacted specifically
      with inhibin. Thus, we report two additional cases of mixed corticomedullary
      tumor of the adrenal gland. Ann Diagn Pathol 5:304-308, 2001. This is a US
      government work. There are no restrictions on its use.

PMID- 11598860
TI  - Pathologic approach to pulmonary hemorrhage.
AB  - The pathologist's approach to pulmonary hemorrhage is outlined. Most cases fall
      into those examples of pulmonary hemorrhage caused by localized sites of
      bleeding, and those examples that fall within the spectrum of diffuse alveolar
      hemorrhage. The histologic evaluation of pulmonary hemorrhage is outlined
      including assessment of fresh hemorrhage in alveolar spaces (including exclusion
      of traumatic hemorrhage related to the procedure) and the presence of hemosiderin
      and its various causes. The most common causes of diffuse alveolar hemorrhage and
      clues to their clinically pathologic diagnosis are discussed.

PMID- 11598861
TI  - Progress in congenital heart disease: decades added to fragile young lives.

PMID- 11598862
TI  - Therapeutic cardiac catheterization for congenital heart disease--a new era in
      pediatric care.
AB  - In recent years, enormous technological advances have occurred that allow
      intervention for many congenital heart defects in the pediatric cardiac
      catheterization laboratory. Therapeutic catheterization procedures, including
      valvuloplasty, angioplasty, stent implantation, coil embolization, and device
      occlusion, are employed to treat heart defects in infants and children. This
      report describes these interventional procedures, outcomes, potential
      complications, and implications for nursing care.

PMID- 11598863
TI  - Primary care in children with congenital heart disease.
AB  - Congenital heart defects, abnormalities in the structural development of the
      heart, occur in approximately 1% of live births. With improved detection,
      diagnosis, medical management, and surgical techniques, the number of children
      surviving with congenital heart disease is increasing. These children require the
      same comprehensive primary care as all other children; however, there are certain
      aspects of primary care that will be affected by the presence of a congenital
      heart defect. This article attempts to clarify the special considerations
      regarding growth and nutrition, development, physical activity, immunizations,
      dental care, use of over-the-counter medications, and perioperative concerns for
      these children. The unique needs of the cardiac transplant patient are beyond the
      scope of this article.

PMID- 11598864
TI  - Pediatric cardiac transplantation: management issues.
AB  - Pediatric heart transplantation is an effective therapeutic modality for children
      with end-stage heart disease. The overall survival of young heart recipients is
      very good: 89% to 92% one year survival. Survival data for the long term
      indicates that pediatric heart recipients have a very good chance of living for
      decades. Advances in immunosuppression have lent optimism for the future. There
      are now alternatives in induction, maintenance, and acute rejection therapy.
      Immunosuppressants are more specific in action and prevent and treat allograft
      rejection with less toxic side effects and decreased morbidity. Acute rejection
      and infection are early complications that reduce in incidence significantly
      after six months post-transplant. Graft coronary artery disease continues to be
      the most significant hurdle to long-term survival. Currently there is a plateau
      in the number of heart transplants performed annually. Lack of available
      pediatric donors plays a large role in the paucity of pediatric transplants. This
      review focuses on the key management issues involved in the care of the pediatric
      heart transplant recipient and incorporates the experiences and protocols of the
      Stanford University Pediatric Heart Transplant Program.

PMID- 11598865
TI  - Parental role in decision making about pediatric cardiac transplantation:
      familial and ethical considerations.
AB  - Parents of children with complex or terminal heart conditions often face
      agonizing decisions about cardiac transplantation. There are differences in the
      level of involvement that parents prefer when making such decisions. The purpose
      of this study was to identify and describe parents' preferences for their roles
      in decisions related to cardiac transplantation. A prospective ethnographic
      method was used to study 24 parents of 15 children prior to their decision of
      accepting or rejecting the transplant option for their children. Findings
      revealed that the style of parent decision making ranged from a desire to make an
      independent, autonomous choice to a wish for an authoritarian, paternalistic
      choice. Nurses and physicians can best support families in this situation,
      showing sensitivity to the steps that parents use to make their decisions. An
      ethical model of decision making is proposed that includes respect for
      differences in beliefs and values of all persons involved in the transplantation
      discussion.

PMID- 11598866
TI  - Current management of infants and children with single ventricle anatomy.
AB  - Children with single ventricle anatomy are among the most complicated and
      challenging patients encountered in pediatric cardiology. Current management
      involves staged surgical procedures, beginning with neonatal palliation and
      followed by a bidirectional cavopulmonary anastomosis in infancy and culminating
      in the Fontan procedure. The Fontan procedure, despite separating the
      circulation, remains a palliative procedure with many long-term concerns. This
      report discusses the staged surgical management of patients with single ventricle
      anatomy and the nursing issues relevant to each stage.

PMID- 11598867
TI  - Pediatric arrhythmias.
AB  - During the past decade, our awareness and understanding of arrhythmias in
      children has expanded immensely. This report discusses the more commonly
      encountered pediatric rhythm disturbances, including sinus node dysfunction, the
      various forms of supraventricular tachycardia, ventricular tachycardia, long QT
      syndrome, and the atrioventricular blocks. The electrocardiographic
      characteristics, electrophysiological mechanisms, clinical presentation, and
      current acute and chronic management options for each are described.

PMID- 11598868
TI  - Health care issues facing adolescents with congenital heart disease.
AB  - The number of children with congenital heart disease surviving beyond adolescence
      is rapidly increasing. Consequently, pediatric health providers not only have to
      address medical issues associated with the cardiac condition but must begin to
      develop programs that assist adolescents and their families in dealing with
      special health care needs for the young patient to successfully move into the
      adult world. Transitional health-related issues facing the adolescent with
      congenital heart disease including medical follow-up, insurability,
      employability, sexuality, and reproduction are described. Discussion about
      advising and counseling both patient and parents is included.

PMID- 11598869
TI  - Childhood injury: a status report.

PMID- 11598870
TI  - Giving children control and toilet training.

PMID- 11598871
TI  - Children affected by violence.

PMID- 11598872
TI  - Depression in children with cancer.
AB  - In this study, children with cancer and healthy students between the ages of 9
      and 13 were investigated in terms of depression status. A demographic data form
      and the Children's Depression Inventory were given to both groups. The research
      group consisted of 50 children with cancer who were followed up in pediatric
      hematology and oncology outpatient clinics at Ankara University. The control
      group was comprised of 50 healthy students who attended Turkozu Timur Primary
      School. It was found that there were significant differences between depression
      scores of children with cancer and children that are healthy. Children with
      cancer have higher depression scores than healthy students.

PMID- 11598874
TI  - Site-specific examination of secondary structure and orientation determination in
      membrane proteins: the peptidic (13)C=(18)O group as a novel infrared probe.
AB  - Detailed site-specific information can be exceptionally useful in structural
      studies of macromolecules in general and proteins in particular. Such information
      is usually obtained from spectroscopic studies using a label/probe that can
      reflect on particular properties of the protein. A suitable probe must not modify
      the native properties of the protein, and should yield interpretable structural
      information, as is the case with isotopic labels used by Fourier transform
      infrared (FTIR) spectroscopy. In particular, 1-(13)C=(18)O labels have been shown
      to relay site-specific secondary structure and orientational information,
      although limited to small peptides. The reason for this limitation is the high
      natural abundance of (13)C and the lack of baseline resolution between the main
      amide I band and the isotope-edited peak. Herein, we dramatically extend the
      utility of isotope edited FTIR spectroscopy to proteins of virtually any size
      through the use of a new 1-(13)C=(18)O label. The double-isotope label virtually
      eliminates any contribution from natural abundance (13)C. More importantly, the
      isotope-edited peak is further red-shifted (in accordance with ab initio Hartree
      Fock calculations) and is now completely baseline resolved from the main amide I
      band. Taken together, this new label enables determination of site specific
      secondary structure and orientation in proteins of virtually any size. Even in
      small peptides 1-(13)C=(18)O is far preferable as a label in comparison to 1
      (13)C=(18)O since it enables analysis without the need for any deconvolution or
      peak fitting procedures. Finally, the results obtained herein represent the first
      stage in the application of site-directed dichroism to the structural elucidation
      of polytopic membrane proteins.

PMID- 11598875
TI  - The pseudomolecule method and the structure of globular proteins. II. The example
      of ribonuclease F1 and T1.
AB  - The pseudomolecule approach to the structure of globular proteins in which a
      small number of water molecules are incorporated into the "molecule" is tested
      again by comparing the ribbon of hydrogen bonds in two proteins, ribonuclease F1
      and T1. These two molecules are 59% homologous and have the same backbone
      conformation both globally and locally. The two ribbons of hydrogen bonds that
      cover the whole of the backbone are conserved with an accuracy of some 95%
      providing that allowance is made for the intrusion into one of the pair of such
      extra factors as the presence of adducts or metal ions, the insertions and the
      absence of a few water molecules from one of the x-ray data sets. Without these
      corrections, the conservation of the ribbon is some 85%. There are 35 conserved
      hydrogen-bonding residues, nearly all of which show many unions to the backbone
      or interactions with the active site. There are 36 point mutations that involve
      one or two hydrogen-bonding side chains and nearly all of these have either none
      or one hydrogen bond to the backbone. These are minor contributors to the ribbon
      of hydrogen bonds. Of the 71 residues involved in these two categories, all but
      six fit into the pseudomolecular picture of the structure of globular proteins.
      The remaining 30 residues almost all contain conserved hydrocarbon side chains
      that may have a second order effect on the structure through their space filling
      effects.

PMID- 11598876
TI  - Global minimization of an off-lattice potential energy function using a chaperone
      based refolding method.
AB  - A global energy minimization method based on what is known about the mechanisms
      of the GroEL/GroES chaperonin system is applied to two 22-mers of an off-lattice
      protein model whose native states are beta-hairpins and which have structural
      similarity to short peptides known to interact strongly with the GroEL substrate
      binding domain. These model substrates have been used by other workers to test
      the effectiveness of a number of global minimization techniques, and are regarded
      as providing a significant challenge. The minimization method developed here is
      progressively elaborated from an initial simple form that targets exposed
      hydrophobic regions for unfolding to include a refolding phase that encourages
      the later recompactification of partly unfolded substrate; this refolding phase
      is seen to be crucial in the successful application of the method. The optimal
      handling of hydrophilic monomers within the model is also systematically
      explored, and it is seen that the best interpretation of their role is one that
      allows the chaperonin model to operate in "proofreading" mode whereby misfolded
      substrates are recognized by their surface exposure of a large proportion of
      hydrophobic monomers. The final version of the model allows native-like
      structures to be found quickly, on average for the two 22-mer substrates after 6
      or 7 chaperone contacts. These results compare very favorably with those that
      have been obtained elsewhere using generic global minimization methods such as
      those based on thermal annealing. The paper concludes with a discussion of the
      place of the technique within the general category of hypersurface deformation
      methods for global minimization, and with suggestions as to how the chaperone
      based method developed here could be elaborated so as to be effective on longer
      substrate chains that give rise to more complex tertiary structures in their
      native states.

PMID- 11598877
TI  - Disparate ionic-strength dependencies of on and off rates in protein-protein
      association.
AB  - Electrostatic interactions have been observed to play important roles in the
      kinetics of protein-protein association. Ionic strength, by its ability to
      modulate the magnitude of electrostatic interactions, has often been conveniently
      used to test their presence. From experiments on a wide range of associating
      proteins, a common feature has emerged: the on rates show strong dependence on
      ionic strength whereas the off rates are relatively insensitive. Here this
      feature is explained by an explicit description of a transition state for the
      association process and the suggestion that this transition is near the final
      bound state of two proteins. The molecular basis of the transition state in the
      bimolecular process lies in the fact that the bound state is characterized by
      local specific (e.g., van der Waals, hydrophobic, and electrostatic)
      interactions, whereas the unbound state is characterized by translational and
      rotational freedom. In the transition state the protein-protein pair encounters a
      free-energy maximum since its translational-rotational entropy is reduced while
      the specific interactions are not yet attained. In this formalism of the protein
      protein association process, the enhancement of on rates by long-range
      electrostatic interactions can be written (analogous to an ordinary transition
      state theory) in the form k(on) = k(0)(on)exp(-G(el)/k(B)T), where G(el) is the
      electrostatic free energy of the transition state.

PMID- 11598878
TI  - Solution structure of hyaluronic acid oligomers by experimental and theoretical
      NMR, and molecular dynamics simulation.
AB  - The conformational properties of hyaluronic acid (HA) oligomers in aqueous
      solution were investigated by combining high-resolution NMR experimental results,
      theoretical simulation of NMR two-dimensional (2D) spectra by Complete Relaxation
      Matrix Analysis (CORMA), and molecular dynamics calculations. New experimental
      findings recorded for the tetra- and hexasaccharides enabled the stiffness of the
      HA and its viscoelastic properties to be interpreted. In particular, rotating
      frame nuclear Overhauser effect spectroscopy spectra provided new information
      about the arrangement of the glycosidic linkage. From (13)C NMR relaxation the
      rotational correlation time (tau(c)) were determined. The tau(c) were employed in
      the calculation of geometrical constraints, by using the MARDIGRAS algorithm.
      Restrained simulated annealing and 1 ns of unrestrained molecular dynamic
      simulations were performed on the hexasaccharide in a box of 1215 water
      molecules. The beta(1 --> 3) and beta(1 --> 4) glycosidic links were found to be
      rigid. The lack of rotational degree of freedom is due to direct and/or water
      mediated interresidue hydrogen bonding. Both single or tandem water bridges were
      found between carboxylate group and N-acetil group. The carboxylate group of
      glucuronic acid is not involved in a direct link with the amide group of N-acetyl
      glucosamine and this facilitated bonding between the residue and the water
      molecules.

PMID- 11598879
TI  - Heat-induced formation of a specific binding site for self-assembled Congo Red in
      the V domain of immunoglobulin L chain lambda.
AB  - Moderate heating (40-50 degrees C) of immunoglobulins makes them accessible for
      binding with Congo Red and some related highly associated dyes. The binding is
      specific and involves supramolecular dye ligands presenting ribbon-like micellar
      bodies. The L chain lambda dimer, which upon heating disclosed the same binding
      requirement with respect to supramolecular dye ligands, was used in this work to
      identify the site of their attachment. Two clearly defined dye-protein (L lambda
      chain) complexes arise upon heating, here called complex I and complex II. The
      first is formed at low temperatures (up to 40-45 degrees C) and hence by a still
      native protein, while the formation of the second one is associated with domain
      melting above 55 degrees C. They contain 4 and 8 dye molecules bound per L chain
      monomer, respectively. Complex I also forms efficiently at high dye concentration
      even at ambient temperature. Complex I and its formation was the object of the
      present studies. Three structural events that could make the protein accessible
      to penetration by the large dye ligand were considered to occur in L chains upon
      heating: local polypeptide chain destabilization, VL-VL domain incoherence, and
      protein melting. Of these three possibilities, local low-energy structural
      alteration was found to correlate best with the formation of complex I. It was
      identified as decreased packing stability of the N-terminal polypeptide chain
      fragment, which as a result made the V domain accessible for dye penetration. The
      19-amino acid N-terminal fragment becomes susceptible to proteolytic cleavage
      after being replaced by the dye at its packing locus. Its splitting from the dye
      protein complex was proved by amino acid sequence analysis. The emptied packing
      locus, which becomes the site that holds the dye, is bordered by strands of amino
      acids numbered 74-80 and 105-110, as shown by model analysis. The character of
      the temperature-induced local polypeptide chain destabilization and its possible
      role in intramolecular antibody signaling is discussed.

PMID- 11598880
TI  - Chemical structure and chain conformation of the water-insoluble glucan isolated
      from Pleurotus tuber-regium.
AB  - A water-insoluble polysaccharide (TM8) was isolated from sclerotium of Pleurotus
      tuber-regium by extraction with 0.5M NaOH aqueous solutions at 120 degrees C. Its
      chemical structure was confirmed by infrared, high performance liquid
      chromatography, gas chromatography, and (13)C NMR in dimethylsulfoxide (DMSO) to
      be composed of beta-(1 --> 3)-D-glucan backbone chain linked with a branched
      glucose, one out of every three glycosyl units being substituted at C6 position.
      The glucan TM8 in DMSO was fractionated by nonsolvent addition method into ten
      fractions, and the solution properties were studied by size exclusion
      chromatography combined with multiangle laser light scattering (SEC-MALLS) and
      viscometry in DMSO at 30 degrees C. The dependencies of intrinsic viscosity [eta]
      and radius of gyration [(s(2)(1/2)(z-2)] on weight-average molecular mass M(w)
      for this glucan were found to be [eta] = (9.24 +/- 0.2) x 10(-2)M(w)(0.51 +/-
      0.02) (cm(3)g(-1)) and [(s(2)(1/2)(z-2)] = (3.67 +/- 0.3) x 10(-2)M(w)(0.56 +/-
      0.02) (nm) in the range of M(w) from 1.07 x 10(4) to 77.4 x 10(4). Based on
      current theories for a wormlike chain, the conformational parameters of the
      glucan TM8 were found to be 408 (nm(-1)) for M(L), 3.1 (nm) for q, and 16.8 for
      C(infinity), suggesting that the polysaccharide exists as a dense random-coil
      chain in DMSO, due to branched structure.

PMID- 11598882
TI  - Cancer-related fatigue: new directions for research. Introduction.

PMID- 11598883
TI  - A patient's perspective on cancer-related fatigue.

PMID- 11598884
TI  - Interferon-mediated fatigue.
AB  - Fatigue is a common side effect of interferon (IFN) therapy, reported in 70-100%
      of patients treated with IFN. The etiology of IFN-mediated fatigue (IMF) is
      multifactorial, with endocrine failure, neuropsychiatric disturbance,
      autoimmunity, and cytokine dysregulation potentially being contributors. Thyroid
      dysfunction, associated with the development of autoantibodies, is seen in 8-20%
      of patients receiving IFN-alpha. IFN-alpha also suppresses the hypothalamic
      pituitary-adrenal axis. In addition, IFN-alpha therapy leads to depression and
      cognitive slowing, and depressed patients are predisposed to develop fatigue.
      Clinical management of IMF is challenging because the syndrome is variable in
      onset and severity and the pathophysiology is poorly understood. Current
      management typically centers on dose reduction, but ancillary nonpharmacologic
      measures may help improve symptoms. Other strategies include antidepressant or
      anxiolytic therapy and treatment of coexisting hypothyroidism. Future studies
      utilizing IFN should include quantitative guidelines for grading and managing
      IMF.

PMID- 11598885
TI  - Management of muscle wasting in cancer-associated cachexia: understanding gained
      from experimental studies.
AB  - BACKGROUND: Cancer-associated cachexia is a syndrome of progressive wasting of
      body energy (adipose) and protein (skeletal muscle) reserves. Cachexia occurs in
      a majority of advanced cancer patients. Extensive loss of muscle mass is one
      factor likely to be associated with fatigue in cancer patients. METHODS: Research
      with animal models of cancer-associated cachexia that have focused on the
      processes of muscle protein synthesis and degradation are reviewed in this
      article. Modulation of the production or action of anabolic and catabolic factors
      known to regulate muscle protein synthesis and degradation have been employed to
      identify causal factors in muscle wasting. RESULTS: Impaired muscle protein
      synthesis and activation of catabolism participate in cancer-associated muscle
      atrophy. The relative roles of multiple factors, including a low level of
      physical activity, poor nutritional status, and secretion of catabolic mediators
      of host or tumor origin, are discussed herein. A diversity of putative mediators
      has been identified, and a number of common themes are beginning to emerge.
      CONCLUSIONS: Multiple distinct catabolic profiles exist in animal models of
      cancer-associated muscle wasting. The presence of these catabolic phenotypes in
      cancer patients must be determined, and the application of successful treatments
      will depend on our ability to determine which categories of patients experience
      the greatest benefit.

PMID- 11598886
TI  - The biologic basis of fatigue.
AB  - In spite of many remarkable advances in our understanding of the mechanisms of
      cancer biology, very little attention has been directed toward mechanisms
      underlying cancer-induced symptoms. Although fatigue is a widely prevalent
      complication of cancer, there is a paucity of both basic and clinical research in
      this area. This article details our current knowledge of mechanisms causing
      cancer-related fatigue and briefly discusses currently available therapeutic
      options. A framework for addressing gaps in our knowledge and recommendations for
      future research directions are proposed.

PMID- 11598887
TI  - The role of cytokines in cancer-related fatigue.
AB  - Fatigue is prominent in cancer patients and probably multifactorial in origin.
      Factors contributing to fatigue include anemia, weight loss, fever, pain,
      medication, and infection. In cancer patients, many of these factors are
      influenced by a frequently disrupted balance between endogenous cytokine levels
      and their natural antagonists. Indeed, cancer cells and the immune system appear
      to overexpress a range of cytokines in patients with malignancies. Some of these
      cytokines act as autocrine or paracrine growth factors for the neoplastic tissue
      while simultaneously causing secondary symptoms related to fatigue. For instance,
      cancer-associated anemia may be due to a blunted erythropoietin response and/or
      cytokines (interleukin-1 [IL-1], IL-6, tumor necrosis factor-alpha [TNF-alpha]),
      which suppress erythropoiesis. Cancerous cachexia, a wasting syndrome and a
      hallmark of cancer, can be attributed to loss of appetite or enhanced energy
      expenditure. Several different interleukins, as well as TNF, interferon-gamma,
      and leukemia inhibitory factor, act as cachectins in animal models. Similarly,
      fever and night sweats are influenced by pyrogenic cytokines. Recently, molecules
      that function as cytokine antagonists have been identified. These molecules may
      be exploitable in combating the components of cancer-related fatigue, and may
      inhibit tumor growth as well.

PMID- 11598888
TI  - Effects of exercise on cancer-related fatigue.
AB  - Cancer patients frequently suffer from fatigue and loss of physical performance.
      Several biologic, psychologic, and social factors have been suggested as
      explanations for the origins of fatigue in this context. In most cases, fatigue
      has a multifactorial genesis. However, recent studies suggest that fatigue may
      originate from alterations in the muscular energetic systems caused by cancer and
      its treatment. Furthermore, there is growing evidence that physical exercise
      programs help prevent the manifestation and reduce the intensity of cancer
      related fatigue. In this article, actual evidence of the relationship between
      fatigue and impairment of physical performance in cancer patients and suggestions
      for new directions for research are discussed.

PMID- 11598889
TI  - Cognitive and mood disturbance as causes and symptoms of fatigue in cancer
      patients.
AB  - Fatigue, cognitive dysfunction, and depression are very common in cancer
      patients. A relationship among the three entities is recognized but poorly
      understood. Factors that contribute to this poor understanding are the subjective
      nature of the symptoms, multiple potential causes, and a lack of reliable
      assessment tools. An understanding of fatigue in cancer patients may benefit from
      studies of chronic fatigue syndrome (CFS) and other nonmalignant diseases
      indicating that cognitive impairment varies with physical and mental fatigue, and
      that symptoms of depression experienced by patients with physical illnesses and
      primary mood disorders are qualitatively different. The multidimensional nature
      of fatigue suggests that interventions should be patient-specific. They could be
      related to lifestyle or involve the use of specific behavioral or pharmacologic
      therapies. As is the case with depression and cognitive disorders, targeted
      interventions against cancer-related fatigue will benefit from a better
      understanding of its potential biologic causes. Consideration of cognitive
      dysfunction and depression complicates the understanding of cancer-related
      fatigue; however, it provides opportunities to assist patients who must deal with
      this serious problem.

PMID- 11598890
TI  - Fatigue management: evidence and guidelines for practice.
AB  - Fatigue has been described as the most common, most debilitating side effect of
      cancer treatment and is frequently reported as a long-term complication of
      treatment as well. Despite the prevalence of fatigue and its profoundly negative
      effect on patients' quality of life, little is known about the specific
      mechanisms that underlie fatigue in cancer patients or how to prevent it and
      treat it effectively. The National Comprehensive Cancer Network (NCCN) Fatigue
      Practice Guidelines Panel has reviewed the available evidence and the consensus
      of practitioners regarding the management of fatigue and has developed clinical
      practice guidelines. These guidelines are presented in this article, with a
      discussion of levels of evidence for interventions recommended by the guidelines.
      Gaps exist in our knowledge of fatigue and further research is needed to support
      the NCCN Practice Guidelines for fatigue; however, there is a developing body of
      knowledge and consensus of clinicians regarding the management of fatigue in
      cancer patients. Additional research directed toward the knowledge gaps would
      strengthen the Practice Guidelines.

PMID- 11598891
TI  - A fatigue clinic in a comprehensive cancer center: design and experiences.
AB  - Cancer-related fatigue is now the most prevalent symptom of cancer, occurring in
      60-90% of patients. Fatigue has been identified by cancer patients as a factor
      influencing functionality and quality of life. Our objectives in developing a
      fatigue specialty clinic at The University of Texas M. D. Anderson Cancer Center
      were to improve our patients' quality of life by decreasing fatigue; educate
      health care providers, patients, and patients' families about cancer-related
      fatigue; develop an appropriate clinical and diagnostic evaluation for this
      symptom; correlate objective measures of fatigue with its clinical evaluation;
      and develop innovative treatment plans for cancer-related fatigue. This article
      describes the general clinic design and operations and the preliminary analysis
      of the first 40 patients evaluated in the fatigue clinic.

PMID- 11598893
TI  - Anemia and fatigue in cancer patients.

PMID- 11598892
TI  - New agents for the treatment of cancer-related fatigue.

PMID- 11598894
TI  - Fatigue during preoperative chemoradiation for resectable rectal cancer.
AB  - BACKGROUND: The aim of this study was to evaluate the severity and patterns of
      fatigue during preoperative chemoradiation therapy for locally advanced rectal
      cancer and determine whether there are predictors for patients who develop severe
      fatigue. METHODS: Seventy-two patients with resectable rectal cancer received
      chemoradiation (total radiation dose, 45 gray/25 fractions to the pelvis;
      continuous infusion of 5-fluorouracil [300 mg/m(2)]). The Brief Fatigue Inventory
      (BFI), a measure that categorizes fatigue severity on a 0-10 scale, was
      administered weekly during treatment. Severe fatigue was defined as 7-10 on the
      "worst level of fatigue" item. Demographics, disease information, toxicities, and
      blood counts were collected. Descriptive statistics, repeated measure analysis of
      variance, and multiple regression were used to examine fatigue and its
      correlates. RESULTS: Fatigue increased in 67% of patients during chemoradiation
      (CTX/XRT). The mean fatigue score increased from 3.16 before treatment to 4.62 at
      the end of treatment. A significant linear trend suggested that fatigue
      progressively got worse during CTX/XRT (F = 16.497, P < 0.001). However, 18% of
      patients experienced severe fatigue before CTX/XRT; this was predicted by
      uncontrolled pain (r(2) = 0.321; F = 16.52; P < 0.001). During CTX/XRT,
      uncontrolled diarrhea was the only predictor for increased fatigue (r(2) = 0.182;
      F = 7.77; P < 0.01). Approximately one-third of patients had severe fatigue,
      which impaired their function at the end of CTX/XRT. CONCLUSIONS: Preoperative
      chemoradiation therapy for patients with rectal cancer was associated with
      progressive fatigue during therapy. Based on identified predictors for fatigue,
      more active pain management before CXT/XRT and bowel management during CTX/XRT
      might reduce cancer-related fatigue in these patients.

PMID- 11598895
TI  - Assessment and epidemiologic issues related to fatigue.
AB  - At The University of Texas M. D. Anderson Cancer Center, a multidisciplinary
      workgroup was assembled to review issues, current research, and areas of future
      research related to the assessment and epidemiology of cancer-related fatigue.
      Interactive discussion facilitated by a moderator determined the major areas of
      focus for future research in this arena. The group's ideas were presented to the
      entire conference following the session. Several gaps in current research related
      to the assessment and epidemiology of cancer-related fatigue were identified.

PMID- 11598896
TI  - Funding ideas for new research.

PMID- 11598897
TI  - Cadherins in neural crest cell development and transformation.
AB  - Cadherins constitute a superfamily of cell adhesion molecules involved in cell
      cell interaction, histogenesis and cellular transformation. They have been
      implicated in the development of various lineages, including derivatives of the
      neural crest. Neural crest cells (NCC) emerge from the dorsal part of the neural
      tube after an epithelio-mesenchymal transition (EMT) and migrate through the
      embryo. After homing and differentiation, NCC give rise to many cell types, such
      as neurons, Schwann cells and melanocytes. During these steps, the pattern of
      expression of the various cadherins studied is very dynamic. Cadherins also
      display plasticity of expression during the transformation of neural crest cell
      derivatives. Here, we review the pattern of expression and the role of the main
      cadherins involved in the development and transformation of neural crest cell
      derivatives.

PMID- 11598898
TI  - PR-39 coordinates changes in vascular smooth muscle cell adhesive strength and
      locomotion by modulating cell surface heparan sulfate-matrix interactions.
AB  - PR-39 is proline-rich peptide produced at sites of tissue injury. While the
      functional properties of this peptide have not been fully defined, PR-39 may be
      an important regulator of processes related to cell-matrix adhesion since it
      reportedly upregulates syndecan-4, which is a critical determinant of focal
      adhesion formation. The ability of PR-39 to modulate the adhesion and
      chemokinetic migration behavior of arterial smooth muscle cells (SMCs) in a
      fashion coordinated with syndecan-4 expression was investigated. Treatment of
      SMCs with PR-39 did not alter syndecan-1 mRNA, but did induce a two-fold increase
      in syndecan-4 mRNA (P < 0.0001) and significantly enhanced cell surface
      expression of both syndecan-4 (P < 0.01) and heparan sulfate (HS) (P < 0.05).
      These observations were consistent with an observed increase in cell-matrix
      adhesive strength (P < 0.05) and a reduction in cell speed (P < 0.01) on
      fibronectin-coated substrates. Incubation of PR-39 treated cells with a soluble
      fibronectin derived heparin-binding peptide, as a competitive inhibitor of
      heparan sulfate/matrix interactions, abolished these effects. These data suggest
      that PR-39 mediated alterations of cell adhesion and motility may be related, in
      part, to the increased expression of heparan sulfate glycosaminoglycans (GAGs)
      that accompany the upregulation of cell surface syndecan-4. Furthermore, this
      investigation supports the notion that factors which control syndecan-4
      expression may play an important role in regulating adhesion related cell
      processes.

PMID- 11598899
TI  - Extracellular matrix regulates induction of alkaline phosphatase expression by
      ascorbic acid in human fibroblasts.
AB  - During wound healing and inflammation, fibroblasts express elevated alkaline
      phosphatase (ALP), but are not in contact with collagen fibrils in the
      fibronectin (FN)-rich granulation tissue. We hypothesized that the extracellular
      matrix (ECM) environment might influence the induction of ALP in fibroblasts.
      Here we tested this hypothesis by studying the ALP-inductive response of normal
      human gingival fibroblasts to ascorbic acid (AsA). AsA induced ALP activity and
      protein in cells in conventional monolayer culture. This induction was inhibited
      by blocking-antibodies to the FN receptor alpha 5 beta 1 integrin and by the
      proline analog 3,4-dehydroproline (DHP). DHP prevented cells from arranging FN
      fibrils into a pericellular network and reduced the activity of cell spreading on
      FN. Plating of cells on FN facilitated the up-regulation by AsA of ALP
      expression, but did not substitute for AsA. In contrast, AsA did not cause ALP
      induction in cells cultured on and in polymerized type I collagen gels. Collagen
      fibrils inhibited the up-regulation by AsA of ALP expression in cells plated on
      FN. These results indicate that the ECM regulates the induction of ALP expression
      by AsA in fibroblasts: FN enables them to express ALP in response to AsA through
      interaction with integrin alpha 5 beta 1, whereas type I collagen fibrils cause
      the suppression of ALP expression and overcome FN.

PMID- 11598900
TI  - Expression of the thrombin receptor (PAR-1) during rat skeletal muscle
      differentiation.
AB  - The serine protease thrombin has been proposed to be involved in neuromuscular
      plasticity. Its specific receptor "protease activated receptor-1" (PAR-1), a G
      protein-coupled receptor, has been shown to be expressed in myoblasts but not
      after fusion (Suidan et al., 1996 J Biol Chem 271:29162-29169). In the present
      work we have investigated the expression of PAR-1 during rat skeletal muscle
      differentiation both in vitro and in vivo. Primary cultures of rat foetal
      skeletal muscle, characterized by their spontaneous contractile activity, were
      used for exploration of PAR-1 by RT-PCR, immunocytochemistry and Western
      blotting. Our results show that PAR-1 mRNA and protein are both present in
      myoblasts and myotubes. Incubation of myotubes loaded with fluo-3-AM in presence
      of thrombin (200 nM) or PAR-1 agonist peptide (SFLLRN, 500 microM), induced the
      intracellular release of calcium indicating the activation of PAR-1. Blockade of
      contractile activity by tetrodotoxin (TTX, 6 nM) did not modify either PAR-1
      synthesis or its cellular localization. Investigation of PAR-1 on rat muscle
      cryostat sections at Day 18 of embryogenesis and postnatal Days 1, 5, and 10
      indicated that this protein is first expressed in the cytoplasm and that it later
      localizes to the membrane. Moreover, its expression correlates with myosin heavy
      chain transitions occurring during post-natal period and is restricted to primary
      fibers. Taken together, these results suggest that PAR-1 expression is not
      related to contractile activity but to myogenic differentiation.

PMID- 11598901
TI  - Differential localization of ErbB2 in different tissues of the rat female
      reproductive tract: implications for the use of specific antibodies for ErbB2
      analysis.
AB  - ErbB2 has been implicated in numerous functions, including normal and aberrant
      development of a variety of tissues. Although no soluble ligand has been
      identified for ErbB2, we have recently shown that ASGP-2, the transmembrane
      subunit of the cell surface glycoprotein Muc4 (also called sialomucin complex,
      SMC), can act as an intramembrane ligand for ErbB2 and modulate its activity.
      Muc4/SMC is abundantly expressed at the apical surface of most epithelia of the
      rat female reproductive tract. Since Muc4/SMC can interact with ErbB2 when they
      are expressed in the same cell and membrane, we investigated whether these two
      proteins are co-expressed and co-localized in tissues of the female reproductive
      tract. Using an anti-ErbB2 antibody from Dako, we found moderate staining at the
      basolateral surface of the oviduct and also around the cell membrane of the most
      superficial and medial layers of the stratified epithelia of the vagina. In
      contrast, Neomarkers neu Ab1 antibody intensely stained the apical surface of the
      epithelium of the oviduct and the medial and basal layers of the stratified
      epithelia of the vagina, substantially overlapping the distribution of Muc4/SMC.
      Furthermore, Muc4/SMC and ErbB2 association in different tissues of the female
      reproductive tract was demonstrated by co-immunoprecipitation analysis.
      Interestingly, phosphorylated ErbB2 detected by anti-phospho-ErbB2 is primarily
      present at the apical surface of the oviduct. Thus, our results show that
      differentially localized forms of ErbB2 are recognized by different antibodies
      and raise interesting questions about the nature of the different forms of ErbB2,
      the mechanism for differential localization, and possible functions of ErbB2 in
      the female reproductive tract. They also raise a cautionary note about the use of
      different ErbB2 antibodies for expression and localization studies.

PMID- 11598902
TI  - Controls of EGF-induced morphological transformation of human bronchial
      epithelial cells.
AB  - Human bronchial epithelial cells, both normal primary (NHBE) and the BEAS-2B
      line, respond to epidermal growth factor (EGF) by extruding lengthy filaments, or
      filapodia. The morphological transformation of BEAS-2B cells maximized at 48 h
      using 1-10 nM EGF. EGF-induced filapodia extension was inhibited by co-exposure
      to transforming growth factor beta, which did not affect tyrosine phosphorylation
      of the EGF receptor (EGFR). Inhibition was also effected by phorbol myristoyl
      acetate (PMA), which reduced the rate of EGFR tyrosine phosphorylation. Dibutyryl
      cAMP had no effect, whereas the protein kinase inhibitor H-89 stimulated the EGF
      response. The ability to regulate cellular responses to EGF by hormonal and
      chemical approaches has implications for current investigations into the roles of
      EGF in lung growth, differentiation, and wound repair.

PMID- 11598903
TI  - Morphine inhibits indolactam V-induced U937 cell adhesion and gelatinase
      secretion.
AB  - We demonstrate that indolactam V, a non-phorbol protein kinase C activator,
      promotes U937 cell attachment to fibronectin, type IV collagen and laminin. In
      the absence of indolactam V, 2-4% of U937 cells attach to all test substrates,
      however, in the presence of 100 nM indolactam V, 25, 16 and 11% of U937 cells
      attach to fibronectin, type IV collagen and laminin, respectively. When added
      concomitantly, 90 microM H-7, a protein kinase C inhibitor, reduces indolactam V
      induced U937 cell adhesion to fibronectin by 91%. Monoclonal antibodies directed
      against both the beta1 and alpha 5 integrin subunits inhibit indolactam V-induced
      U937 cell adhesion to fibronectin by 62 and 52%, respectively. Indolactam V also
      promotes homotypic aggregation in U937 cells, which is blocked with either anti
      ICAM or anti-LFA-1 antibodies. In addition, indolactam V promotes U937 cell
      secretion of a 92 kDa gelatinase as demonstrated by zymography. In the presence
      of low levels of morphine (10 nM-1.0 microM), the U937 cell attachment to matrix
      proteins was not significantly affected. However, in the presence of 10 microM
      morphine, the indolactam V treated cells exhibit a 71-74% reduction in cell
      adhesion to the matrix proteins. Further, 10 microM morphine also blocks
      indolactam V-induced homotypic aggregation and gelatinase secretion. The
      inhibitory effect of morphine on cell-matrix adhesion and gelatinase secretion
      was not inhibited by the opiate receptor antagonist naloxone (1 microM). While 10
      microM naloxone did partially counteract the effect of 10 microM morphine on U937
      cell attachment, this effect was likely non-specific since 10 microM naloxone
      alone increased cell adhesion. Supporting this conclusion, PCR analysis revealed
      that U937 cells do not express the mu high affinity morphine receptor. Also,
      indolactam V did not induce mu receptor expression, suggesting that morphine acts
      on U937 cells in a non-specific fashion.

PMID- 11598904
TI  - Oxygen-mediated regulation of skeletal muscle satellite cell proliferation and
      adipogenesis in culture.
AB  - Major problems in stem cell biology revolve around defining the developmental
      potential of cell populations and understanding how their potential is maintained
      or progressively restricted. Oxygen (O(2)) is an obvious environmental factor
      which has received little attention in culturing skeletal muscle progenitor
      cells. In this work, we examine the effects of O(2) levels on the developmental
      potential, proliferative capacity, and phenotype of the adult skeletal muscle
      fiber progenitor population (satellite cells), and cell lines that model
      multipotential embryonic paraxial mesoderm from which skeletal muscle develops.
      Both satellite cell proliferation and survival of mature fibers increased in
      physiologic (6%) O(2) vs. non-physiologic 20% O(2) used in virtually all
      traditional cell culture. Six percent O(2) conditions also accelerated the up
      regulation of multiple MyoD family myogenic regulatory factors (MRFs). An
      unexpected finding was that fiber-adherent satellite cells could assume a non
      myogenic phenotype. By the criteria of molecular markers and gross lipid
      accumulation, satellite cells were found to assume an adipocyte phenotype, and
      did so more prominently in 20% O(2) than in physiologic O(2). Selection of the
      adipogenic fate and execution of adipogenesis by multipotential mesenchymal cell
      lines was also dramatically higher in traditional 20 vs. 6% O(2), and decreased
      adipogenesis in physiologic O(2) was associated with significantly less
      expression of the adipogenic regulator, PPAR gamma. These results suggest that
      regulatory pathways affected by O(2) are important for satellite cell
      proliferation, execution of cell fate, and parent muscle survival in culture, and
      so may play a role in vivo under normal or pathologic conditions.

PMID- 11598905
TI  - Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G, and
      proteinase-3: a role for inflammatory cells in tumor invasion and angiogenesis.
AB  - Gelatinase A (MMP-2), a matrix metalloproteinase (MMP) involved in tumor invasion
      and angiogenesis, is secreted as an inactive zymogen (proMMP-2) and activated by
      proteolytic cleavage. Here we report that polymorphonuclear neutrophil (PMN)
      derived elastase, cathepsin G, and proteinase-3 activate proMMP-2 through a
      mechanism that requires membrane-type 1 matrix metalloproteinase (MT1-MMP)
      expression. Immunoprecipitation of human PMN-conditioned medium with a mixture of
      antibodies to elastase, cathepsin G, and proteinase-3 abolished proMMP-2
      activation, whereas individual antibodies were ineffective. Incubation of HT1080
      cells with either purified PMN elastase or cathepsin G or proteinase-3 resulted
      in dose-and time-dependent proMMP-2 activation. Addition of PMN-conditioned
      medium to MT1-MMP expressing cells resulted in increased proMMP-2 activation and
      in vitro invasion of extracellular matrix (ECM), but had no effect with cells
      that express no MT1-MMP. MMP-2 activation by PMN-conditioned medium or purified
      elastase was blocked by the elastase inhibitor alpha(1)-antitrypsin but not by
      Batimastat, an MMP inhibitor, showing that elastase activation of MMP-2 is not
      mediated by MMP activities. The PMN-conditioned medium-induced increase in cell
      invasion was blocked by Batimastat as well as by alpha(1)-antitrypsin, showing
      that PMN serine proteinases trigger a proteinase cascade that entails proMMP-2
      activation: this gelatinase is the downstream effector of the proinvasive
      activity of PMN proteinases. These findings indicate a novel role for PMN
      mediated inflammation in a variety of tissue remodeling processes including tumor
      invasion and angiogenesis.

PMID- 11598906
TI  - Insulin-like growth factors (IGF-I and IGF-II) inhibit C2 skeletal myoblast
      differentiation and enhance TNF alpha-induced apoptosis.
AB  - IGF-I and IGF-II are thought to be unique in their ability to promote muscle cell
      differentiation. Murine C2 myoblasts differentiate when placed into low serum
      media (LSM), accompanied by increased IGF-II and IGF binding protein-5 (IGFBP-5)
      production. Addition of 20 ng/ml TNF alpha on transfer into LSM blocked
      differentiation, IGF-II and IGFBP-5 secretion and induced apoptosis. We,
      therefore, wished to assess whether IGFs could protect against the effects of TNF
      alpha. Neither inhibition of differentiation or induction of apoptosis was
      rescued by co-incubation with IGF-I or IGF-II. A lower dose of TNF alpha (1
      ng/ml) while not inducing apoptosis still inhibited myoblast differentiation by
      56% +/- 12, (P < 0.001), indicating that induction of apoptosis is not the sole
      mechanism by which TNF alpha inhibits myoblast differentiation. Addition of IGF-I
      or IGF-II alone reduced differentiation by 49% +/- 15 and 33% +/- 20,
      respectively, (P < 0.001), although neither induced apoptosis. For muscle cells
      to differentiate, they must arrest in G0. We established that addition of IGF-I,
      IGF-II or TNF alpha to the myoblasts promoted proliferation. The myoblasts could
      not exit the cell cycle as efficiently as controls and differentiation was thus
      reduced. Unexpectedly, co-incubation of IGF-I or IGF-II with 1 ng/ml TNF alpha
      enhanced the inhibition of differentiation and induced apoptosis. In the absence
      of apoptosis we show an association between IGF-induced inhibition of
      differentiation and increased IGFBP-5 secretion. These results indicate that the
      effects of the IGFs on muscle may depend on the cytokine environment. In the
      absence of TNF alpha, the IGFs delay differentiation and promote myoblast
      proliferation whereas in the presence of TNF alpha the IGFs induce apoptosis.

PMID- 11598907
TI  - Regulation of expression and activity of four PKC isozymes in confluent and
      mechanically stimulated UMR-108 osteoblastic cells.
AB  - The transcript (mRNA), protein levels, enzyme activity, and cellular localization
      of four protein kinase C (PKC) isozymes identified in rat osteogenic sarcoma
      cells (UMR-108) were studied at confluent density and during mechanical stress
      (cyclic stretch). Western blot analysis indicated that growth to confluent
      density significantly increased the protein levels of cPKC-alpha (11.6-fold),
      nPKC-delta (5.3-fold), and nPKC-epsilon (22.0-fold) but not aPKC-zeta. Northern
      blot analysis indicated a significant (2.3-fold) increase in the 10 kb transcript
      of cPKC-alpha, a slight (1.3-fold) increase in that of nPKC-epsilon but no
      detectable change in that of the remaining isozymes. Enzyme activity assays of
      the individually immunoprecipitated isozymes yielded detectable kinase activity
      only for PKC-alpha, PKC-delta, and PKC-epsilon and only in confluent cells,
      corroborating the selective increase of these isozymes at confluent density. The
      UMR-108 cells showed a dramatic orientation response to mechanical stress with
      cell reshaping and alignment of the cell long axis perpendicular to the axis of
      force, remodeling of the actin cytoskeleton, and the appearance of multiple
      peripheral sites which stained for actin, vinculin, and PKC in separate
      experiments. Longer term mechanical stress beyond 24 h, however, resulted in no
      significant change in the mRNA level, protein level, or enzyme activity of any of
      the four PKC isozymes investigated. The results indicate that there are isozyme
      selective increases in the protein levels of PKC isozymes of osteoblastic UMR-108
      cells upon growth to confluence which may be regulated at the transcriptional or
      the post-transcriptional level. The results from UMR-108 cells support the
      earlier proposal (Carvalho RS, Scott JE, Suga DM, Yen EH. 1994. J Bone Miner Res
      9(7):999-1011) that PKC could be involved in the early phase of
      mechanotransduction in osteoblasts through the activation of focal adhesion
      assembly/disassembly and the remodeling of the actin cytoskeleton.

PMID- 11598908
TI  - Modulation of the heteromeric Kir4.1-Kir5.1 channels by P(CO(2)) at physiological
      levels.
AB  - Several inward rectifier K(+) (Kir) channels are pH-sensitive, making them
      potential candidates for CO(2) chemoreception in cells. However, there is no
      evidence showing that Kir channels change their activity at near physiological
      level of P(CO(2)), as most previous studies were done using high concentrations
      of CO(2). It is known that the heteromeric Kir4.1-Kir5.1 channels are highly
      sensitive to intracellular protons with pKa value right at the physiological pH
      level. Such a pKa value may allow these channels to regulate membrane potentials
      with modest changes in P(CO(2)). To test this hypothesis, we studied the Kir4.1
      Kir5.1 currents expressed in Xenopus oocytes and membrane potentials in the
      presence and absence of bicarbonate. Evident inhibition of these currents (by
      approximately 5%) was seen with P(CO(2)) as low as 8 torr. Higher P(CO(2)) levels
      (23-60 torr) produced stronger inhibitions (by 30-40%). The inhibitions led to
      graded depolarizations (5-45 mV with P(CO(2)) 8-60 torr). Similar effects were
      observed in the presence of 24 mM bicarbonate and 5% CO(2). Indeed, the Kir4.1
      Kir5.1 currents were enhanced with 3% CO(2) and suppressed with 8% CO(2) in
      voltage clamp, resulting in hyper- (-9 mV) and depolarization (16 mV) in current
      clamp, respectively. With physiological concentration of extracellular K(+), the
      Kir4.1-Kir5.1 channels conduct substantial outward currents that were similarly
      inhibited by CO(2) as their inward rectifying currents. These results therefore
      indicate that the heteromeric Kir4.1-Kir5.1 channels are modulated by a modest
      change in P(CO(2)) levels. Such a modulation alters cellular excitability, and
      enables the cell to detect hypercapnia and hypocapnia in the presence of
      bicarbonate.

PMID- 11598909
TI  - Role of phospholipases A(2) in growth-dependent changes in prostaglandin release
      from 3T6 fibroblasts.
AB  - Previously, we reported a growth-dependent change in prostaglandin production as
      a consequence of a marked growth-dependent alteration in arachidonic acid (AA)
      mobilization from phospholipids. Our present results show that fetal calf serum
      (FCS) and 4 beta-phorbol-12-myristate acetate (PMA) caused an enhancement of
      phospholipase A(2) (PLA(2)) activity in the membrane fraction of non-confluent
      cells allowing PLA(2) access to its substrate and the release of AA. Western blot
      analysis has shown that FCS and PMA increased secreted PLA(2) (sPLA(2))
      expression in non-confluent 3T6 fibroblast cultures. Moreover, FCS and PMA
      induced dithiothreitol-sensitive and bromoenol lactone-sensitive PLA(2)
      activities in cytosol and membrane fraction. However, these stimuli did not
      modify significantly the PLA(2) activity in both fractions when 3T6 fibroblasts
      reached a high cell density. This could be associated with the impairment of AA
      mobilization in these cell culture conditions. On the other hand, we observed
      that FCS and PMA induced the same prostaglandin H synthase-2 induction in non
      confluent and confluent culture conditions. Moreover, the prostaglandin E(2)
      levels reached in cell culture supernatants were independent of the degree of
      confluence when AA was added exogenously. These results suggest that the changes
      of intracellular distribution of PLA(2) activity of sPLA(2) and iPLA(2)
      stimulated by exogenous stimuli may be controlled by cell density conditions
      which constitute an important mechanism in the regulation of prostaglandin
      release.

PMID- 11598911
TI  - Elements of butterfly wing patterns.
AB  - The color patterns on the wings of butterflies are unique among animal color
      patterns in that the elements that make up the overall pattern are individuated.
      Unlike the spots and stripes of vertebrate color patterns, the elements of
      butterfly wing patterns have identities that can be traced from species to
      species, and typically across genera and families. Because of this identity it is
      possible to recognize homologies among pattern elements and to study their
      evolution and diversification. Individuated pattern elements evolved from non
      individuated precursors by compartmentalization of the wing into areas that
      became developmentally autonomous with respect to color pattern formation.
      Developmental compartmentalization led to the evolution of serially repeated
      elements and the emergence of serial homology. In these compartments, serial
      homologues were able to acquire site-specific developmental regulation and this,
      in turn, allowed them to diverge morphologically. Compartmentalization of the
      wing also reduced the developmental correlation among pattern elements. The
      release from this developmental constraint, we believe, enabled the great
      evolutionary radiation of butterfly wing patterns. During pattern evolution, the
      same set of individual pattern elements is arranged in novel ways to produce
      species-specific patterns, including such adaptations as mimicry and camouflage.

PMID- 11598912
TI  - The tetrapod limb: a hypothesis on its origin.
AB  - A wrist joint and structures typical of the hand, such as digits, however, are
      absent in [Eustenopteron] (Andrews and Westoll, '68, p 240). Great changes must
      have been undergone during evolution of the ankle joint; the small number of
      large bones in the fin must somehow have developed into a large number of small
      bones, and it is very difficult to draw homologies in this region, or even be
      certain of what is being compared (Andrews and Westoll, '68, p 268). The tetrapod
      limb is one of the major morphological adaptations that facilitated the
      transition from an aquatic to a terrestrial lifestyle in vertebrate evolution. We
      review the paleontological evidence for the fin-limb transition and conclude that
      the innovation associated with evolution of the tetrapod limb is the zeugopodial
      mesopodial transition, i.e., the evolution of the developmental mechanism that
      differentiates the distal parts of the limb (the autopodium, i.e., hand or foot)
      from the proximal parts. Based on a review of tetrapod limb and fish fin
      development, we propose a genetic hypothesis for the origin of the autopodium. In
      tetrapods the genes Hoxa-11 and Hoxa-13 have locally exclusive expression domains
      along the proximal-distal axis of the limb bud. The junction between the distal
      limit of Hoxa-11 expression and of the proximal limit of Hoxa-13 expression is
      involved in establishing the border between the zeugopodial and autopodial
      anlagen. In zebrafish, the expression domains of these genes are overlapping and
      there is no evidence for an autopodial equivalent in the fin skeleton. We propose
      that the evolution of the derived expression patterns of Hoxa-11 and Hoxa-13 may
      be causally involved in the origin of the tetrapod limb.

PMID- 11598913
TI  - Developmental modularity and the evolutionary diversification of arthropod limbs.
AB  - Segmentation is one of the most salient characteristics of arthropods, and
      differentiation of segments along the body axis is the basis of arthropod
      diversification. This article evaluates whether the evolution of segmentation
      involves the differentiation of already independent units, i.e., do segments
      evolve as modules? Because arthropod segmental differentiation is commonly
      equated with differential character of appendages, we analyze appendages by
      comparing similarities and differences in their development. The comparison of
      arthropod limbs, even between species, is a comparison of serially repeated
      structures. Arthropod limbs are not only reiterated along the body axis, but
      limbs themselves can be viewed as being composed of reiterated parts. The
      interpretation of such reiterated structures from an evolutionary viewpoint is
      far from obvious. One common view is that serial repetition is evidence of a
      modular organization, i.e., repeated structures with a common fundamental
      identity that develop semi-autonomously and are free to diversify independently.
      In this article, we evaluate arthropod limbs from a developmental perspective and
      ask: are all arthropod limbs patterned using a similar set of mechanisms which
      would reflect that they all share a generic coordinate patterning system? Using
      Drosophila as a basis for comparison, we find that appendage primordia,
      positioned along the body using segmental patterning coordinates, do indeed have
      elements of common identity. However, we do not find evidence of a single
      coordinate system shared either between limbs or among limb branches. Data
      concerning the other diagnostic of developmental modularity--semi-autonomy of
      development--are not currently available for sufficient taxa. Nonetheless, some
      data comparing patterns of morphogenesis provide evidence that limbs cannot
      always be temporally or spatially decoupled from the development of their
      neighbors, suggesting that segment modularity is a derived character.

PMID- 11598914
TI  - Altered timing of the extracellular-matrix-mediated epithelial-mesenchymal
      interaction that initiates mandibular skeletogenesis in three inbred strains of
      mice: development, heterochrony, and evolutionary change in morphology.
AB  - Subtle changes in embryonic development are a source of significant morphological
      alterations during evolution. The mammalian mandibular skeleton, which originates
      from the cranial neural crest, is a complex structure comprising several
      components that interact late in embryogenesis to produce a single functional
      unit. It provides a model system in which individual developmental events at the
      basis of population-level evolutionary change can be investigated experimentally.
      Inbred mouse strains exhibit obvious morphological differences despite the
      relatively short time since their divergence from one another. Some of these
      differences can be traced to small changes in the timing of early developmental
      events such as the formation of the cellular condensations that initiate
      skeletogenesis. This paper examines an even earlier event for changes in timing,
      the epithelial-mesenchymal interaction(s) required to initiate chondrogenesis of
      Meckel's cartilage and osteogenesis of the dentary bone. Using three inbred
      strains of mice (CBA, C3H and C57) we found that, within each strain, cartilage
      and bone are induced at the same time and by the same (mandibular) epithelium,
      that chondrogenesis and osteogenesis are initiated by a matrix-mediated
      epithelial-mesenchymal interaction, and that timing of the interactions differs
      among the three inbred strains. These results are discussed with respect to the
      possible molecular basis of such temporal shifts in inductive interactions and
      how such studies can be used to shed light on heterochrony as a mechanism of
      evolutionary change in morphology.

PMID- 11598915
TI  - Development of an evolutionarily novel structure: fibroblast growth factor
      expression in the carapacial ridge of turtle embryos.
AB  - The turtle shell, an evolutionarily novel structure, contains a bony exoskeleton
      that includes a dorsal carapace and a ventral plastron. The development of the
      carapace is dependent on the carapacial ridge (CR), a bulge in the dorsal flank
      that contains an ectodermal structure analogous to the apical ectodermal ridge
      (AER) of the developing limb (Burke. 1989a. J Morphol 199:363-378; Burke. 1989b.
      Fortschr Zool 35:206-209). Although the CR is thought to mediate the initiation
      and outgrowth of the carapace, the mechanisms of shell development have not been
      studied on the molecular level. Here, we present data suggesting that carapace
      formation is initiated by co-opting genes that had other functions in the
      ancestral embryo, specifically those of limb outgrowth. However, there is
      divergence in the signaling repertoire from that involved in limb initiation and
      outgrowth. In situ hybridizations with antisense riboprobes derived from Trionyx
      spiniferous fibroblast growth factor-10 (tfgf10) and Trachemys scripta (T.
      scripta) fibroblast-growth factor 8 (tfgf8) cDNAs were performed on sections of
      early T. scripta embryos (< 30 days). Expression of tfgf10 was localized to the
      mesenchyme subjacent to the ectoderm of the CR. In the chick limb bud, FGF10 is
      known to be expressed in the early limb-forming mesenchyme and is capable of
      inducing FGF8 in the AER to initiate the outgrowth of the limb bud. Although the
      expression of tfgf8 was found in the AER of the developing turtle limb, it was
      not seen in the CR. Thus, the initiation of the carapace is in agreement with
      FGF10 expression in the CR, but FGF8 does not appear to have a role in mediating
      early carapace outgrowth.

PMID- 11598916
TI  - Using heterochrony plots to detect the dissociated coevolution of characters.
AB  - The comparison of developmental sequences among species is notoriously difficult.
      Here, heterochrony plots are introduced as a new graphic method to detect
      temporal shifts in the development of characters in pair-wise species
      comparisons. Plotting the timing of character development in one species against
      the timing of character development in another species allows us to compare a
      principally unlimited number of characters simultaneously and can detect whether
      suites of characters are dissociated from one another or not. Such heterochrony
      plots can be embedded into a comparative phylogenetic analysis in order to
      establish whether observed patterns of character codissociation are indeed due to
      their dissociated coevolution. Comparative phylogenetic analysis may also reveal
      multiple independent events of dissociated coevolution of the same suite of
      characters in a certain lineage, suggesting that the characters of this suite
      reciprocally constrain their evolutionary modifiability, thereby forming a unit
      of evolution. This ability to identify units of evolution is a prerequisite for
      assessing the validity of recently proposed scenarios, suggesting that modules of
      development and/or function tend to act as units of evolution. Starting from a
      detailed heterochrony plot comparing development in the direct developing frog
      Eleutherodactylus coqui and in the biphasically developing frog Discoglossus
      pictus, this comparative approach is illustrated focusing on the evolution of
      development of limbs, the nervous system and the pharyngeal arches in amphibians.

PMID- 11598917
TI  - Expression and function of Xenopus laevis p75(NTR) suggest evolution of
      developmental regulatory mechanisms.
AB  - Neurotrophins signal through two different classes of receptors, members of the
      trk family of receptor tyrosine kinases, and p75 neurotrophin receptor
      (p75(NTR)), a member of the tumor necrosis factor receptor family. While
      neurotrophin binding to trks results in, among other things, increased cell
      survival, p75(NTR) has enigmatically been implicated in promoting both survival
      and cell death. Which of these two signals p75(NTR) imparts depends on the
      specific cellular context. Xenopus laevis is an excellent system in which to
      study p75(NTR) function in vivo because of its amenability to experimental
      manipulation. We therefore cloned partial cDNAs of two p75(NTR) genes from
      Xenopus, which we have termed p75(NTR)a and p75(NTR)b. We then cloned two
      different cDNAs, both of which encompass the full coding region of p75(NTR)a.
      Early in development both p75(NTR)a and p75(NTR)b are expressed in developing
      cranial ganglia and presumptive spinal sensory neurons, similar to what is
      observed in other species. Later, p75(NTR)a expression largely continues to
      parallel p75(NTR) expression in other species. However, Xenopus p75(NTR)a is
      additionally expressed in the neuroepithelium of the anterior telencephalon, all
      layers of the retina including the photoreceptor layer, and functioning axial
      skeletal muscle. Finally, misexpression of full length p75(NTR) and each of two
      truncated mutants in developing retina reveal that p75(NTR) probably signals for
      cell survival in this system. This result contrasts with the reported role of
      p75(NTR) in developing retinae of other species, and the possible implications of
      this difference are discussed.

PMID- 11598918
TI  - Receptor protein tyrosine phosphatases regulate retinal ganglion cell axon
      outgrowth in the developing Xenopus visual system.
AB  - Receptor protein tyrosine phosphatases (RPTPs) are regulators of axon outgrowth
      and guidance in a variety of different vertebrate and invertebrate systems. Three
      RPTPs, CRYP-alpha, PTP-delta, and LAR, are expressed in overlapping but distinct
      patterns in the developing Xenopus retina, including expression in retinal
      ganglion cells (RGCs) as they send axons to the tectum (Johnson KG, Holt CE.
      2000. Expression of CRYP-alpha, LAR, PTP-delta, and PTP-rho in the developing
      Xenopus visual system. Mech Dev 92:291-294). In order to examine the role of
      these RPTPs in visual system development, putative dominant negative RPTP mutants
      (CS-CRYP-alpha, CS-PTP-delta, and CS-LAR) were expressed either singly or in
      combination in retinal cells. No effect was found on either retinal cell fate
      determination or on gross RGC axon guidance to the tectum. However, expression of
      these CS-RPTP constructs differentially affected the rate of RGC axon outgrowth.
      In vivo, expression of all three CS-RPTPs or CS-PTP-delta alone inhibited RGC
      axon outgrowth, while CS-LAR and CS-CRYP-alpha had no significant effect. In
      vitro, expression of CS-CRYP-alpha enhanced neurite outgrowth, while CS-PTP-delta
      inhibited neurite outgrowth in a substrate-dependent manner. This study provides
      the first in vivo evidence that RPTPs regulate retinal axon outgrowth.

PMID- 11598919
TI  - Optical detection of neuromodulatory effects of conditioned taste aversion in the
      pond snail Lymnaea stagnalis.
AB  - Multiple site optical recording was used to analyze the neural activity changes
      caused by conditioned taste aversion (CTA) training in the pond snail Lymnaea
      stagnalis. In response to electrical stimulation of the median lip nerve, which
      transmits chemosensory signals of appetitive taste to the central nervous system,
      we optically detected large numbers of spikes in several parts of the buccal
      ganglion. The effects of CTA training on the spike responses were examined in two
      areas of the ganglion where the most active neural responses occurred. In one
      area (termed Area I) that included the N1 medial (N1M) cells, a class of central
      pattern generator interneurons involved in feeding behavior, the number of spikes
      in a period 1500-2000 ms after median lip nerve stimulation was significantly
      reduced in conditioned animals compared to control animals. In another area
      (termed Area II) positioned between buccal motoneurons, the B3 and B4CL (cluster)
      cells, the evoked spike responses were unaffected by CTA training. These results,
      taken together with our previous results indicating an enhancement of an
      inhibitory input to the N1M cells during CTA, suggest that an appetitive taste
      signal transmitted to the N1M cells through the median lip nerves is suppressed
      during CTA, resulting in a decrease of the feeding response.

PMID- 11598920
TI  - Cellular competence plays a role in photoreceptor differentiation in the
      developing Xenopus retina.
AB  - Factors in the environment appear to be responsible for inducing many of the cell
      fates in the retina, including, for example, photoreceptors. Further, there is a
      conserved order of histogenesis in the vertebrate retina, suggesting that a
      temporal mechanism interacts in the control of cellular determination. The
      temporal mechanism involved could result from different inducing signals being
      released at different times. Alternatively, the inducing signals might be present
      at many stages, but an autonomous clock could regulate the competence of cells to
      respond to them. To differentiate between these mechanisms, cells from young
      embryonic retinas were dissociated and grown together with those from older
      embryos, and the timing of photoreceptor determination assayed. Young cells
      appeared uninfluenced by older cells, expressing photoreceptor markers on the
      same time schedule as when cultured alone. A similar result was obtained when the
      heterochronic mixing was done in vivo by grafting a small plug of optic vesicle
      from younger embryos into older hosts. Even the graft cells at the immediate
      margin of the transplant failed to express photoreceptor markers earlier than
      normal, despite their being in contact with older, strongly expressing host
      cells. We conclude that retinal progenitors intrinsically acquire the ability to
      respond to photoreceptor-inducing cues by a mechanism that runs on a cell
      autonomous schedule, and that the conserved order of histogenesis is based in
      part on this competence clock.

PMID- 11598922
TI  - Looking for long-term effects from prenatal exposures to anticonvulsants.

PMID- 11598921
TI  - Immunoelectron microscopic localization of the neural recognition molecules L1,
      NCAM, and its isoform NCAM180, the NCAM-associated polysialic acid, beta1
      integrin and the extracellular matrix molecule tenascin-R in synapses of the
      adult rat hippocampus.
AB  - We have investigated the possibility that morphologically different excitatory
      glutamatergic synapses of the "trisynaptic circuit" in the adult rodent
      hippocampus, which display different types of long-term potentiation (LTP), may
      express the immunoglobulin superfamily recognition molecules L1 and NCAM, the
      extracellular matrix molecule tenascin-R, and the extracellular matrix receptor
      constituent beta1 integrin in a differential manner. The neural cell adhesion
      molecules L1, NCAM (all three major isoforms), NCAM180 (the largest major isoform
      with the longest cytoplasmic domain), beta1 integrin, polysialic acid (PSA)
      associated with NCAM, and tenascin-R were localized by pre-embedding
      immunostaining procedures in the CA3/CA4 region (mossy fiber synapses) and in the
      dentate gyrus (spine synapses) of the adult rat hippocampus. Synaptic membranes
      of mossy fiber synapses where LTP is expressed presynaptically did not show
      detectable levels of immunoreactivity for any of the molecules/epitopes studied.
      L1, NCAM, and PSA, but not NCAM180 or beta1 integrin, were detectable on axonal
      membranes of fasciculating mossy fibers. In contrast to mossy fiber synapses,
      spine synapses in the outer third of the molecular layer of the dentate gyrus,
      which display postsynaptic expression mechanisms of LTP, were both immunopositive
      and immunonegative for NCAM, NCAM180, beta1 integrin, and PSA. Those spine
      synapses postsynaptically immunoreactive for NCAM or PSA also showed
      immunoreactivity on their presynaptic membranes. NCAM180 was not detectable
      presynaptically in spine synapses. L1 could not be found in spine synapses either
      pre- or postsynaptically. Also, the extracellular matrix molecule tenascin-R was
      not detectable in synaptic clefts of all synapses tested, but was amply present
      between fasciculating axons, axon-astrocyte contact areas, and astrocytic gap
      junctions. Differences in expression of the membrane-bound adhesion molecules at
      both types of synapses may reflect the different mechanisms for induction and/or
      maintenance of synaptic plasticity.

PMID- 11598923
TI  - Importance of model organisms in understanding the biology and genetic basis of
      human nonsyndromic neural tube defects.

PMID- 11598924
TI  - Association of prenatal phenobarbital and phenytoin exposure with genital
      anomalies and menstrual disorders.
AB  - BACKGROUND: Animal studies demonstrated that early exposure to phenobarbital
      decreases reproductive function. This study investigates whether prenatal
      exposure to these anticonvulsants affects human genital tract development.
      METHODS: Genital anomalies at birth were studied retrospectively in 90
      phenobarbital-exposed, 108 phenobarbital plus phenytoin-exposed, and 198 matched
      control infants. Of this group, 72 drug-exposed males, 75 drug-exposed females,
      and 147 matched control subjects participated in a follow-up and were interviewed
      at age 19-35. Differences between groups were tested by chi-square and t-tests.
      RESULTS: A total of 15% of the phenobarbital-exposed boys versus 2.8% control
      boys had undescended testes at birth. More anticonvulsant-exposed (24%) than
      control males (11%) had received medical treatment for genital anomalies.
      Anticonvulsant-exposed females more often had irregularities in menstrual cycles
      (31% vs. 17%) and bleeding (15% vs. 3%) and reported more problems during
      pregnancy. CONCLUSIONS: Prenatal exposure to anticonvulsants seems to induce
      minor genital anomalies and may affect reproductive function.

PMID- 11598925
TI  - Multifactorial genetics of exencephaly in SELH/Bc mice.
AB  - BACKGROUND: The SELH/Bc mouse strain has 10-30% exencephaly and is an animal
      model for human neural tube closure defects. This study examined the number of
      causative genes, their dominance relationships, and linkage map positions.
      METHODS: The SELH/Bc strain (S) was crossed to the normal LM/Bc strain (L) and
      frequencies of exencephaly were observed in the F(1), BC(1), and F(2)
      generations. 102 F(2) males were individually testcrossed by SELH/Bc. The
      extremes, the 10 highest and 10 zero exencephaly-producing F(2) sires, were typed
      for 109 SSLP marker loci in a genome screen. Next, the resultant five provisional
      chromosomal regions were tested for linkage in 31 F(2) exencephalic embryos.
      Finally, 12 males, SS or LL for the Chr 13 region on an LM/Bc background, were
      testcrossed by SELH/Bc. RESULTS: The exencephaly frequencies in the F(1) (0.3%),
      BC(1) (4.4%), and F(2) (3.7%), and the distribution of F(2) males' testcross
      values (0-15.5%), indicated that the high risk of exencephaly in SELH/Bc is due
      to the cumulative effect of two or three loci. Linkage studies indicated the
      location of semidominant exencephaly-risk genes on Chr 13 near D13Mit13 (P <
      0.001), Chr 5 near D5Mit168 (P < 0.025), and possibly Chr 11 near D11Mit10 (P <
      0.07). The gene on Chr 13, Exen1, and the strong role of other loci were
      confirmed by the congenic males. CONCLUSIONS: The high risk of exencephaly in
      SELH/Bc mice is caused by the cumulative effect of two to three semidominant
      genes. Candidate genes include Msx2, Madh5, Ptch, and Irx1 (Chr 13) and Actb and
      Rac1 (Chr 5).

PMID- 11598926
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibition of coronary development is
      preceded by a decrease in myocyte proliferation and an increase in cardiac
      apoptosis.
AB  - BACKGROUND: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular
      toxicity, culminating in edema, hemorrhage, and mortality in piscine, avian, and
      mammalian embryos. To elucidate the mechanism of the cardiovascular
      teratogenicity of TCDD, we used a chick embryo model to determine whether TCDD
      alters coronary artery development and whether this alteration was associated
      with apoptosis and/or changes in myocyte proliferation. METHODS: Fertile chicken
      eggs were injected with corn oil (control), 0.24, or 0.40 pmol TCDD/g in corn oil
      before incubation. To evaluate effects of TCDD on differentiation of coronary
      arteries, chick embryo hearts from incubation days 8 (D8), D10, and D12 were
      stained with anti-alpha-smooth muscle actin. Myocyte proliferation was measured
      by BrdU incorporation on D6, 8, 10, and 12 after TCDD treatment. In addition,
      temporal and spatial patterns of apoptosis were detected by TUNEL on D3, D5, D6,
      D8, and D10, and immunohistochemistry was used to identify the origin of
      apoptotic cells on D6. RESULTS: TCDD increased apoptosis in structures where cell
      death normally occurs, including the outflow tract, endocardial cushion of the
      atrioventricular canal, and dorsal mesocardium, peaking in intensity on D6.
      Immunohistochemistry revealed that cells undergoing TCDD-induced apoptosis in the
      dorsal mesocardium were not neural or epicardial in origin. On D8 and D10 TCDD
      reduced myocyte proliferation. On D10, TCDD reduced coronary artery size and on
      D10 and D12 TCDD induced a dose-dependent decrease in coronary artery number.
      CONCLUSIONS: The reduction of myocyte proliferation by TCDD preceded the
      reduction in coronary artery number and size, suggesting that changes in coronary
      development may be a consequence of reduced myocyte proliferation and a thinner
      ventricle wall. The peak of TCDD-induced increase in apoptosis occurred even
      earlier in embryo development and thus may contribute to changes in myocyte
      proliferation, coronary development, and cardiac structural malformations;
      however, a cause-and-effect relationship between apoptosis and these other events
      has yet to be established.

PMID- 11598927
TI  - Transplacental exposure to methylene blue initiates teratogenesis in the mouse:
      preliminary evidence for a mechanistic implication of cyclic GMP pathway
      disruption.
AB  - BACKGROUND: The vital dye methylene blue (MB) has been shown to be teratogenic
      when injected into the amnion in the second trimester. On the other hand, the
      teratogenic potential of transplacental exposure to MB has not been determined.
      METHODS: MB was administered subcutaneously to ICR (CD-1) mice at 0, 35, 50, 60,
      or 70 mg/kg on gestation day 8 (plug day = day 0). Teratological assessments were
      carried out at term gestation, on gestation day 18. Since MB inhibits soluble
      guanylate cyclase enzyme activity, zaprinast (ZPN), a selective cGMP
      phosphodiesterase type V inhibitor, was administered to prevent developmental
      disorders initiated by MB at 50 mg/kg. RESULTS: There was a dose-dependent
      increment of embryolethality. MB treatment also produced axial skeleton and
      neural tube defects. Coadministration of ZPN (20 mg/kg per three times) abolished
      completely MB-induced neural tube defects and reduced by one-half the incidence
      of fetuses exhibiting axial skeletal defects. ZPN did not provide protection
      against the embryocidal effects of MB. CONCLUSIONS: This study showed that
      transplacental exposure to MB is teratogenic in the mouse. Coadministration of
      ZPN prevented partly MB-induced teratogenesis, which supports the hypothesis that
      imbalance of cGMP pathway accounts, in part, for the teratogenicity of MB.

PMID- 11598928
TI  - Dysmorphology in the Bible and the Talmud.
AB  - This article enumerates the congenital anomalies mentioned in the Bible and the
      Talmud, the two holiest and oldest texts in Judaism. Most of these conditions
      were described to regulate attributes that would disqualify a Priest from
      performing religious rituals in the Temple in Jerusalem. However, the cultural
      atmosphere in Biblical and Talmudical times was one in which physical deformity
      did not necessarily evoke a negative aesthetic reaction, an assumption of ill
      health, or the expectation of economic dependence.

PMID- 11598941
TI  - Combined confocal and wide-field high-resolution cytometry of fluorescent in situ
      hybridization-stained cells.
AB  - BACKGROUND: The recently developed technique of high-resolution cytometry (HRCM)
      enables automated acquisition and analysis of fluorescent in situ hybridization
      (FISH)-stained cell nuclei using conventional wide-field fluorescence microscopy.
      The method has now been extended to confocal imaging and offers the opportunity
      to combine the advantages of confocal and wide-field modes. METHODS: We have
      automated image acquisition and analysis from a standard inverted fluorescence
      microscope equipped with a confocal module with Nipkow disk and a cooled digital
      CCD camera. The system is fully controlled by a high-performance computer that
      performs both acquisition and related on-line image analysis. The system can be
      used either for an automatic two (2D) and three-dimensional (3D) analysis of FISH
      stained interphase nuclei or for a semiautomatic 3D analysis of FISH-stained
      cells in tissues. The user can select which fluorochromes are acquired using wide
      field mode and which using confocal mode. The wide-field and confocal images are
      overlaid automatically in computer memory. The developed software compensates
      automatically for both chromatic color shifts and spatial shifts caused by
      switching to a different imaging mode. RESULTS: Using the combined confocal and
      wide-field HRCM technique, it is possible to take advantage of both imaging
      modes. Images of some dyes (such as small hybridization dots or counterstain
      images of individual interphase nuclei) do not require confocal quality and can
      be acquired quickly in wide-field mode. On the contrary, images of other dyes
      (such as chromosome territories or counterstain images of cells in tissues) do
      require improved quality and are acquired in confocal mode. The dual-mode
      approach is two to three times faster compared with the single-mode confocal
      approach and the spectrum of its applications is much broader compared with both
      single-mode confocal and single-mode wide-field systems. CONCLUSIONS: The
      combination of high speed specific to the wide-field mode and high quality
      specific to the confocal mode gives optimal system performance.

PMID- 11598942
TI  - Automated topographical cell proliferation analysis.
AB  - BACKGROUND: Cell proliferation is often studied using the incorporation of
      bromodeoxyuridine (BrdU). Immunohistochemical staining is then used to detect
      BrdU in the nucleus. To circumvent the observer bias and labor-intensive nature
      of manually counting BrdU-labeled nuclei, an automated topographical cell
      proliferation analysis method is developed. METHODS: Sections stained with
      fluorescein-labeled anti-BrdU and counterstained with To-Pro-3 are scanned using
      confocal laser scanning microscopy (CLSM). For every point in the image, the
      nucleus density of BrdU-labeled nuclei and the total nucleus density of the
      neighborhood of that point are calculated from the BrdU and the To-Pro-3 signal,
      respectively. The ratio of these densities gives an indication of the amount of
      cell proliferation at that point. The automated measure is validated by comparing
      it with the ratio of BrdU-stained nuclei to the total number of nuclei obtained
      from a manual count. RESULTS: A positive correlation is found between the
      automated measure and the ratios calculated from the manual counting (r = 0.86, P
      < 0.001). Calculating the topographical cell proliferation using the automated
      method is faster and does not suffer from interobserver variability. CONCLUSIONS:
      Automated topographical cell proliferation analysis is a fast method to
      objectively find differences in cell proliferation within a tissue. This can be
      visualized by a topographical map that corresponds to the tissue under study.

PMID- 11598943
TI  - Micronuclei assay by laser scanning cytometry.
AB  - BACKGROUND: The micronuclei (MN) assay is used to assess the chromosomal/mitotic
      spindle damage induced by ionizing radiation or mutagenic agents in vivo or in
      vitro. Because visual scoring of MN is cumbersome semi-automatic procedures that
      relay either on flow cytometry or image analysis were developed: both offer some
      advantages but also have shortcomings. METHODS: In the present study laser
      scanning cytometer (LSC), the instrument that combines analytical capabilities of
      flow and image cytometry, has been adapted for quantitative analysis of MN. The
      micronucleation of human breast carcinoma MCF-7 and leukemic HL-60 and U-937
      cells was induced by in vitro treatment with mitomycin C. Cellular DNA was
      stained with propidium iodide (PI), protein was counterstained with fluorescein
      isothiocyanate (FITC). Two approaches were used to detect MN: (a) the threshold
      contour was set based on the data from the photosensor measuring red fluorescence
      of PI and MN were identified on the bivariate PI versus PI/FITC fluorescence
      distributions by their characteristic position; (b) the threshold contour was set
      on the data from the sensor measuring FITC fluorescence which made it possible,
      using the LSC software dedicated for FISH analysis, to assay both the frequency
      and DNA content of individual MN within each measured cell. RESULTS: The
      capability of LSC to relocate MN for visual examination was useful to confirm
      their identification. Visual identification of MN combined with their
      multiparameter characterization that took into an account their DNA content and
      protein/DNA ratio made it possible establish the gating parameters that excluded
      objects that were not MN; 93.3+/-3.3 events within the selected gate were MN. It
      was also possible to successfully apply FISH software to characterize individual
      cells with respect to quantity of MN residing in them. The percentage of MN
      assayed by LSC correlated well with that estimated visually by microscopy, both
      for MCF-7 (r = 0.93) and HL-60 cells (r = 0.87). CONCLUSIONS: LSC can be used to
      obtain unbiased estimate of MN frequencies. Unlike flow cytometry, it also allows
      one to characterize individual cells with respect to frequency and DNA content of
      MN residing in these cells. These analytical capabilities of LSC may be helpful
      not only to score MN but also to study mechanisms by which clastogenic agents
      induce MN.

PMID- 11598944
TI  - Multiplexed fluorescent bead-based immunoassays for quantitation of human
      cytokines in serum and culture supernatants.
AB  - BACKGROUND: An increasing volume of data suggests a relationship between cytokine
      levels in human body fluids and disease pathogenesis. Traditionally, many
      individual assays would be performed to measure the large number of known
      cytokines and determine their associations with disease. A new technique for the
      simultaneous measurement of multiple cytokines in cell culture supernatants by
      fluorescent microsphere-based flow cytometry was adapted to human sera. METHODS:
      Multiplexed sandwich immunoassays for eight cytokines were developed by coupling
      cytokine-specific capture antibodies to beads with different emission spectra.
      The binding of biotinylated detection antibodies bound with a streptavidin
      conjugated fluorochrome was analyzed. Recovery of "spiked" cytokines,
      sensitivity, and variability of the assays were evaluated. In addition, the
      results of the bead assays were compared with the results of commercial enzyme
      linked immunosorbent assays (ELISAs) that used the same antibody pairs. RESULTS:
      Correlations of the bead assays and the ELISAs were 0.974 (n = 18) for
      supernatant samples and 0.859 (n = 28) for serum samples. High, false-positive
      values observed with some sera, assumed to be produced by heterophilic
      antibodies, were reduced by preincubation with a cocktail of animal sera.
      CONCLUSIONS: Fluorescent bead-based immunoassays can be used to quantitate
      multiple cytokines in human sera and contribute to an understanding of the role
      of cytokines in disease processes. This methodology is applicable to many
      combinations of purified analytes and high-affinity antibodies. Published 2001
      Wiley-Liss, Inc.

PMID- 11598945
TI  - Probability binning comparison: a metric for quantitating univariate distribution
      differences.
AB  - BACKGROUND: Comparing distributions of data is an important goal in many
      applications. For example, determining whether two samples (e.g., a control and
      test sample) are statistically significantly different is useful to detect a
      response, or to provide feedback regarding instrument stability by detecting when
      collected data varies significantly over time. METHODS: We apply a variant of the
      chi-squared statistic to comparing univariate distributions. In this variant, a
      control distribution is divided such that an equal number of events fall into
      each of the divisions, or bins. This approach is thereby a mini-max algorithm, in
      that it minimizes the maximum expected variance for the control distribution. The
      control-derived bins are then applied to test sample distributions, and a
      normalized chi-squared value is computed. We term this algorithm Probability
      Binning. RESULTS: Using a Monte-Carlo simulation, we determined the distribution
      of chi-squared values obtained by comparing sets of events derived from the same
      distribution. Based on this distribution, we derive a conversion of any given chi
      squared value into a metric that is analogous to a t-score, i.e., it can be used
      to estimate the probability that a test distribution is different from a control
      distribution. We demonstrate that this metric scales with the difference between
      two distributions, and can be used to rank samples according to similarity to a
      control. Finally, we demonstrate the applicability of this metric to ranking
      immunophenotyping distributions to suggest that it indeed can be used to
      objectively determine the relative distance of distributions compared to a single
      control. CONCLUSION: Probability Binning, as shown here, provides a useful metric
      for determining the probability that two or more flow cytometric data
      distributions are different. This metric can also be used to rank distributions
      to identify which are most similar or dissimilar. In addition, the algorithm can
      be used to quantitate contamination of even highly-overlapping populations.
      Finally, as demonstrated in an accompanying paper, Probability Binning can be
      used to gate on events that represent significantly different subsets from a
      control sample. Published 2001 Wiley-Liss, Inc.

PMID- 11598946
TI  - Probability binning comparison: a metric for quantitating multivariate
      distribution differences.
AB  - BACKGROUND: While several algorithms for the comparison of univariate
      distributions arising from flow cytometric analyses have been developed and
      studied for many years, algorithms for comparing multivariate distributions
      remain elusive. Such algorithms could be useful for comparing differences between
      samples based on several independent measurements, rather than differences based
      on any single measurement. It is conceivable that distributions could be
      completely distinct in multivariate space, but unresolvable in any combination of
      univariate histograms. Multivariate comparisons could also be useful for
      providing feedback about instrument stability, when only subtle changes in
      measurements are occurring. METHODS: We apply a variant of Probability Binning,
      described in the accompanying article, to multidimensional data. In this
      approach, hyper-rectangles of n dimensions (where n is the number of measurements
      being compared) comprise the bins used for the chi-squared statistic. These hyper
      dimensional bins are constructed such that the control sample has the same number
      of events in each bin; the bins are then applied to the test samples for chi
      squared calculations. RESULTS: Using a Monte-Carlo simulation, we determined the
      distribution of chi-squared values obtained by comparing sets of events from the
      same distribution; this distribution of chi-squared values was identical as for
      the univariate algorithm. Hence, the same formulae can be used to construct a
      metric, analogous to a t-score, that estimates the probability with which
      distributions are distinct. As for univariate comparisons, this metric scales
      with the difference between two distributions, and can be used to rank samples
      according to similarity to a control. We apply the algorithm to multivariate
      immunophenotyping data, and demonstrate that it can be used to discriminate
      distinct samples and to rank samples according to a biologically-meaningful
      difference. CONCLUSION: Probability binning, as shown here, provides a useful
      metric for determining the probability with which two or more multivariate
      distributions represent distinct sets of data. The metric can be used to identify
      the similarity or dissimilarity of samples. Finally, as demonstrated in the
      accompanying paper, the algorithm can be used to gate on events in one sample
      that are different from a control sample, even if those events cannot be
      distinguished on the basis of any combination of univariate or bivariate
      displays. Published 2001 Wiley-Liss, Inc.

PMID- 11598947
TI  - Frequency difference gating: a multivariate method for identifying subsets that
      differ between samples.
AB  - BACKGROUND: In multivariate distributions (for example, in 3- or more color flow
      cytometric datasets), it can become difficult or impossible to identify
      populations that differ between samples based only on a combination of univariate
      or bivariate displays. Indeed, it is possible that such differences can only be
      identified in "n"-dimensional space, where "n" is the number of parameters
      measured. Therefore, computer assisted identification of such differences is
      necessary. Such a method could be used to identify responses (i.e., by comparing
      cell samples before and after stimulation) in exquisite detail by allowing
      complete analysis of the collected data on only those events which have
      responded. METHODS: Multivariate Probability Binning can be used to compare
      different datasets to identify the distance and statistical significance of a
      difference between the distributions. An intermediate step in the algorithm
      provides access to the actual locations within the n-dimensional comparison which
      are most different between the distributions. Gates based on collections of hyper
      rectangular bins can then be applied to datasets, thereby selecting those events
      (or clusters of events) that are different between samples. We term this process
      Frequency Difference Gating. RESULTS: Frequency Difference Gating was used in
      several test scenarios to evaluate its utility. First, we compared PBMC subsets
      identified by solely by immunofluorescence staining: based on this training data
      set, the algorithm automatically generated an accurate forward and side-scatter
      gate to identify lymphocytes. Second, we applied the algorithm to identify subtle
      differences between CD4 memory subsets based on 8-color immunophenotyping data.
      The resulting 3-dimensional gate could resolve cells subsets much more frequent
      in one subset compared to the other; no combination of two-dimensional gates
      could accomplish this resolution. Finally, we used the algorithm to compare B
      cell populations derived from mice of different ages or strains, and found that
      the algorithm could find very subtle differences between the populations.
      CONCLUSION: Frequency Difference Gating is a powerful tool that automates the
      process of identifying events comprising underlying differences between samples.
      It is not a clustering tool; it is not meant to identify subsets in
      multidimensional space. Importantly, this method may reveal subtle changes in
      small populations of cells, changes that only occur simultaneously in multiple
      dimensions in such a way that identification by univariate or bivariate analyses
      is impossible. Finally, the method may significantly aid in the analysis of high
      order multivariate data (i.e., 6-12 color flow cytometric analyses), where
      identification of differences between datasets becomes so time-consuming as to be
      impractical. Published 2001 Wiley-Liss, Inc.

PMID- 11598948
TI  - Use of the monoclonal antibody DAKO-ERbeta (8D5-1) to measure oestrogen receptor
      beta in breast cancer cells.
AB  - BACKGROUND: Oestrogen receptor beta (ERbeta) is highly homologous with the
      classical ER (known now as ERalpha). The exact role of ERbeta in breast cancer
      and its contribution in influencing patient response to endocrine therapy remains
      unclear. The aim of this study was to develop and evaluate a flow cytometric
      method for the detection of ERbeta in breast cancer cells using the DAKO
      monoclonal anti-ERbeta 8D5-1 antibody. METHODS: MCF7 cells were used as a
      positive control and U937 as a negative control for titration of the antibody.
      Cell lines and tumour samples were fixed with 1% paraformaldehyde and
      permeabilised with 0.5% saponin prior to flow cytometric analysis. RESULTS: A ten
      fold difference in expression of ERbeta within the different breast cell lines
      studied was found. Confirmation of antibody specificity against ERbeta protein by
      Western blot analysis detected a single band at approximately 65kDa. ERbeta
      immunopositive nuclei were identified in MCF7 cells by immunohistochemistry.
      CONCLUSIONS: DAKO ERbeta 8D5-1 antibody is specific for ERbeta protein and does
      not cross react with ERalpha protein. Using this antibody, ERbeta can be detected
      and accurately quantified in cell lines and solid breast tumours by flow
      cytometry.

PMID- 11598949
TI  - Bivariate analysis of cellular DNA versus RNA content by laser scanning cytometry
      using the product of signal subtraction (differential fluorescence) as a separate
      parameter.
AB  - BACKGROUND: The cytometric methods of bivariate analysis of cellular RNA versus
      DNA content have limitations. The method based on the use of metachromatic
      fluorochrome acridine orange (AO) requires rigorous conditions of the equilibrium
      staining whereas pyronin Y and Hoechst 33342 necessitate the use of an instrument
      that provides two-laser excitation, including the ultraviolet (UV) light
      wavelength. METHODS: Phytohemagglutinin (PHA)-stimulated human lymphocytes were
      deposited on microscope slides and fixed. DNA and double-stranded (ds) RNA were
      stained with propidium iodide (PI) and protein was stained with BODIPY 630/650-X
      or fluorescein isothiocyanate (FITC). Cellular fluorescence was measured with a
      laser scanning cytometer (LSC). The cells were treated with RNase A and their
      fluorescence was measured again. The file-merge feature of the LSC was used to
      record the cell PI fluorescence measurements prior to and after the RNase
      treatment in list mode, as a single file. The integrated PI fluorescence
      intensity of each cell after RNase treatment was subtracted from the fluorescence
      intensity of the same cell measured prior to RNase treatment. This RNase-specific
      differential value of fluorescence (differential fluorescence [DF]) was plotted
      against the cell fluorescence measured after RNase treatment or against the
      protein-associated BODIPY 630/650-X or FITC fluorescence. RESULTS: The
      scattergrams were characteristic of the RNA versus DNA bivariate distributions
      where DF represented cellular ds RNA content and fluorescence intensity of the
      RNase-treated cells, their DNA content. The distributions were used to correlate
      cellular ds RNA content with the cell cycle position or with protein content.
      CONCLUSIONS: One advantage of this novel approach based on the recording and
      plotting of DF is that only the RNase -specific fraction of cell fluorescence is
      measured with no contribution of nonspecific components (e.g., due to the
      emission spectrum overlap or stainability of other than RNA cell constituents).
      Another advantage is the method's simplicity, which ensues from the use of a
      single dye, the same illumination, and the same emission wavelength detection
      sensor for measurement of both DNA and ds RNA. The method can be extended for
      multiparameter analysis of cell populations stained with other fluorochromes of
      the same-wavelength emission but targeted (e.g., immunocytochemically) for
      different cell constituents.

PMID- 11598950
TI  - Flow cytometric determination of telomere length.

PMID- 11598952
TI  - Making a vertebrate limb: new players enter from the wings.
AB  - What initiates vertebrate limb development and induces limbs to form where they
      do? For several years the answer to this intriguing question has been framed in
      terms of a working model that limb induction depends on a dialogue between two
      members of the Fibroblast Growth Factor (FGF) family of intercellular signaling
      molecules, FGF8 and FGF10. Now, a recent paper has written roles for signals
      encoded by WNT genes, the vertebrate relatives of the Drosophila wingless gene,
      into the script.

PMID- 11598953
TI  - Wingless can't fly so it hitches a ride with dynein.
AB  - Asymmetric RNA localization is required for many developmental processes in a
      wide range of organisms. For example, wingless and pair-rule transcripts are
      localized to the apical membrane of polarized cells. It has been unclear,
      however, if this localization is important for biological activity and, in
      addition, how the transcripts are transported. Two recent studies (1,2) have
      identified cis-elements and trans-acting factors that are required for the
      asymmetric localization of mRNAs. Correct localization is shown to be required
      for biological activity, and a mechanism of RNA transport involving the
      microtubule motor dynein has been revealed.

PMID- 11598954
TI  - Analysing gene function after duplication.
AB  - After gene duplication, mutations cause the gene copies to diverge. The classical
      model predicts that these mutations will generally lead to the loss of function
      of one gene copy; rarely, new functions will be created and both duplicate genes
      are conserved. In contrast, under the subfunctionalization model both duplicates
      are preserved due to the partition of different functions between the duplicates.
      A recent study provides support for the subfunctionalization model, identifying
      several expressed gene duplicates common to humans and mice that contain regions
      conserved in one duplicate but variable in the other (and vice versa). We discuss
      both the methodology used in this study and also how gene phylogeny may lead to
      additional evidence for the importance of subfunctionalization in the evolution
      of new genes.

PMID- 11598955
TI  - Glial cell development in the Drosophila embryo.
AB  - Glial cells play a central role in the development and function of complex
      nervous systems. Drosophila is an excellent model organism for the study of
      mechanisms underlying neural development, and recent attention has been focused
      on the differentiation and function of glial cells. We now have a nearly complete
      description of glial cell organization in the embryo, which enables a systematic
      genetic analysis of glial cell development. Most glia arise from neural stem
      cells that originate in the neurogenic ectoderm. The bifurcation of glial and
      neuronal fates is under the control of the glial promoting factor glial cells
      missing. Differentiation is propagated through the regulation of several
      transcription factors. Genes have been discovered affecting the terminal
      differentiation of glia, including the promotion glial-neuronal interactions and
      the formation of the blood-nerve barrier. Other roles of glia are being explored,
      including their requirement for axon guidance, neuronal survival, and signaling.

PMID- 11598956
TI  - Midline and laterality defects: left and right meet in the middle.
AB  - The aim of this review is to summarize some of the recent advances in molecular
      embryology that help to explain the pathogenesis of holoprosencephaly (HPE), or
      its related malformation in model organisms, cyclopia, and laterality defects in
      humans, derived from detailed analysis of similar malformations in animal models.
      Recently, defects in several developmental pathways including those operated by
      the Sonic hedgehog and Nodal signaling factors have been implicated as causes of
      HPE or laterality defects in humans. Here we summarize the findings in animal
      models that indicate that both defects can be explained by mechanisms that relate
      to the proper development of the axial midline in vertebrates. Published 2001
      John Wiley & Sons, Inc.

PMID- 11598957
TI  - Organ formation in Drosophila: specification and morphogenesis of the salivary
      gland.
AB  - The Drosophila salivary gland has emerged as an outstanding model system for the
      process of organ formation. Many of the component steps, from initial regional
      specification through cell specialization and morphogenesis, are known and many
      of the genes required for these different processes have been identified. The
      salivary gland is a relatively simple organ; the entire gland comprises of only
      two major cell types, which derive from a single contiguous primordium. Salivary
      cells cease dividing once they are specified, and organ growth is achieved simply
      by an increase in size of individual cells, thus eliminating concerns about the
      potential unequal distribution of determinants during mitosis. Drosophila
      salivary glands form by the same cellular mechanisms as organs in higher
      organisms, including regulated cell shape changes, cell intercalation and
      directed cell migration. Thus, learning how these events are coordinated for
      tissue morphogenesis in an organism for which the genetic and molecular tools are
      unsurpassed should provide excellent paradigms for dissecting related processes
      in the more intricate organs of more complicated species.

PMID- 11598958
TI  - Leaving the neighborhood: molecular mechanisms involved during epithelial
      mesenchymal transition.
AB  - Several molecular mechanisms contribute directly and mechanically to the loss of
      epithelial phenotype. During epithelial-mesenchymal transition (EMT), adherens
      junctions and desmosomes are at least partially dissociated. At the same time, a
      massive cytoskeleton reorganization takes place, involving the rho family and the
      remodeling of the actin microfilament mesh. Numerous pathways have been described
      in vitro that control phenotype transition in specific cell models. In vivo
      developmental studies suggest that transcriptional control, activated by a
      specific pathway involving Ras, Src and potentially the Wnt pathway, is an
      essential step. Recent functional and localization experiments indicate that the
      slug/snail family of transcription factors functions overall as an epithelial
      phenotype repressor and could represent a key EMT contributor.

PMID- 11598959
TI  - Shaping the metaphase chromosome: coordination of cohesion and condensation.
AB  - Recent progress in our understanding of mitotic chromosome dynamics has been
      accelerated by the identification of two essential protein complexes, cohesin and
      condensin. Cohesin is required for holding sister chromatids (duplicated
      chromosomes) together from S phase until the metaphase-to-anaphase transition.
      Condensin is a central player in chromosome condensation, a process that
      initiates at the onset of mitosis. The main focus of this review is to discuss
      how the mitotic metaphase chromosome is assembled and shaped by a precise balance
      between the cohesion and condensation machineries. We argue that, in different
      eukaryotic organisms, the balance of cohesion and condensation is adjusted in
      such a way that the size and shape of the resulting chromosomes are best suited
      for their accurate segregation.

PMID- 11598960
TI  - 14-3-3 proteins: key regulators of cell division, signalling and apoptosis.
AB  - The 14-3-3 proteins constitute a family of conserved proteins present in all
      eukaryotic organisms so far investigated. These proteins have attracted interest
      because they are involved in important cellular processes such as signal
      transduction, cell-cycle control, apoptosis, stress response and malignant
      transformation and because at least 100 different binding partners for the 14-3-3
      proteins have been reported. Although the exact function of 14-3-3 proteins is
      still unknown, they are known to (1) act as adaptor molecules stimulating protein
      protein interactions, (2) regulate the subcellular localisation of proteins and
      (3) activate or inhibit enzymes. In this review, we discuss the role of the 14-3
      3 proteins in three cellular processes: cell cycle control, signal transduction
      and apoptosis. These processes are regulated by the 14-3-3 proteins at multiple
      steps. The 14-3-3 proteins have an overall inhibitory effect on cell cycle
      progression and apoptosis, whereas in signal transduction they may act as
      stimulatory or inhibitory factors. This article contains supplementary material
      which may be viewed at the BioEssays website at
      http://www.interscience.wiley.com/jpages/0265-9247/Suppmat/23/v23_10.936.

PMID- 11598961
TI  - Paradox of Bcl-2 (and p53): why may apoptosis-regulating proteins be irrelevant
      to cell death?
AB  - Although the Bcl-2 family members and p53 are involved in the regulation of
      apoptosis, the status of apoptotic machinery (eg caspases) plays a major role in
      determining the mode and timing of cell death. If the apoptotic machinery is
      lost, inhibited, or intrinsically inactivated, the "death stars", Bcl-2 and p53,
      may become irrelevant to cell death. In this light, high levels of Bcl-2 may
      indicate that downstream apoptotic pathways are still functional. This explains
      why Bcl-2 overexpression can be a marker of chemosensitivity and favorable
      prognosis in certain cancers and why retention of wild-type p53 may manifest
      inactivation of caspases in aggressive cancers.

PMID- 11598962
TI  - Bridging the gap between developmental systems theory and evolutionary
      developmental biology.
AB  - Many scientists and philosophers of science are troubled by the relative
      isolation of developmental from evolutionary biology. Reconciling the science of
      development with the science of heredity preoccupied a minority of biologists for
      much of the twentieth century, but these efforts were not corporately successful.
      Mainly in the past fifteen years, however, these previously dispersed integrating
      programmes have been themselves synthesized and so reinvigorated. Two of these
      more recent synthesizing endeavours are evolutionary developmental biology (EDB,
      or "evo-devo") and developmental systems theory (DST). While the former is a
      bourgeoning and scientifically well-respected biological discipline, the same
      cannot be said of DST, which is virtually unknown among biologists. In this
      review, we provide overviews of DST and EDB, summarize their key tenets, examine
      how they relate to one another and to the study of epigenetics, and survey the
      impact that DST and EDB have had (and in future should have) on biological theory
      and practice.

PMID- 11598963
TI  - The hydroid Hydractinia: a versatile, informative cnidarian representative.
AB  - The Cnidaria represent the most ancient eumetazoan phylum. Members of this group
      possess typical animal cells and tissues such as sensory cells, nerve cells,
      muscle cells and epithelia. Due to their unique phylogenetic position, cnidarians
      have traditionally been used as a reference group in various comparative studies.
      We propose the colonial marine hydroid, Hydractinia, as a convenient, versatile
      platform for basic and applied research in developmental biology, reproduction,
      immunology, environmental studies and more. In addition to being a typical
      cnidarian representative, Hydractinia offers many practical and theoretical
      advantages: studies that are feasible in Hydra like regeneration, pattern
      regulation, and cell renewal from stem cells, can be supplemented by genetic
      analyses and classical embryology in Hydractinia. Metamorphosis of the planula
      larva of Hydractinia can be used as a model for cell activation and communication
      and the presence of a genetically controlled allorecognition system makes it a
      suitable model for comparative immunology. Most importantly, Hydractinia may be
      manipulated at most aspects of its (short) life cycle. It has already been the
      subject of many studies in various disciplines, some of which are discussed in
      this essay.

PMID- 11598964
TI  - Cell & tissue morphogenesis.

PMID- 11598965
TI  - Is it likely that superhuman intelligence has evolved anywhere in the universe?

PMID- 11598966
TI  - Why biologists should support the exploration of Mars.
AB  - Physicists, chemists and geologists in the USA and Europe propose that the search
      for extraterrestrial life is an important justification for the exploration of
      Mars. Biologists, however, much more excited by the advent of the postgenome
      sequencing era, in general display little enthusiasm for planetary exploration.
      We argue that the search for traces of life on Mars represents a major thought
      provoking challenge for the life sciences that should be taken up by the
      biological community.

PMID- 11598969
TI  - Prevalence of cigarette smoking by occupation and industry in the United States.
AB  - BACKGROUND: This study was undertaken to estimate the most recent prevalence of
      cigarette smoking by occupation and industry in the US, using the data from the
      third National Health and Nutrition Examination Survey (NHANES III), 1988-1994.
      METHODS: Included in NHANES III are data on the cigarette smoking status,
      occupation, industry, and other demographic information of US non
      institutionalized civilians obtained through household interview surveys. The
      study population included 20,032 adults aged 17 years and older. To estimate the
      prevalence of cigarette smoking across occupation and industry groups, we used
      the Survey Data Analysis (SUDAAN) software. RESULTS: The prevalence of cigarette
      smoking was highest among material moving occupations, construction laborers, and
      vehicle mechanics and repairers. The lowest smoking prevalence was found among
      teachers. Among industry groups, the construction industry had the highest
      prevalence of cigarette smoking. CONCLUSIONS: These findings provide information
      useful for targeting education activities focusing on adverse health effects of
      cigarette smoking and also for indirect adjustments in analysis of morbidity and
      mortality by occupation. Am. J. Ind. Med. 40:233-239, 2001. Published 2001 Wiley
      Liss, Inc.

PMID- 11598970
TI  - Non-malignant asbestos-related diseases in Brazilian asbestos-cement workers.
AB  - BACKGROUND: Production of asbestos-cement products in Brazil started in the
      1940s, peaked in the 60-70s and is still an active industry. This study was
      designed to assess the non-malignant effects of asbestos exposure in the asbestos
      cement industry in Brazil. METHODS: A group of 828 former asbestos-cement workers
      enrolled in a cross-sectional and cohort study of respiratory morbidity,
      submitted to a detailed occupational history, respiratory symptoms questionnaire,
      spirometry, PA chest x-ray, and high resolution computed chest tomography (HRCT).
      Asbestos exposure was assessed by years of exposure, cumulative exposure (a semi
      quantitative method), and latency time from first exposure. Asbestosis and
      pleural thickening were assessed according to HRCT criteria. RESULTS: Asbestosis
      was present in 74 (8.9%) and pleural thickening in 246 (29.7%). Using the HRCT as
      the "best available evidence", it was shown that were more false negatives than
      false positives in the x-ray readings for parenchymal (21.6% false negatives,
      4.2% false positives) and pleural (26.0% false negatives, 14.4% false positives)
      diseases due to asbestos. Latency time from first exposure was the best predictor
      for both asbestosis and pleural thickening. Subjects in the higher exposure
      groups presented lower levels of lung function. Obstructive defects were
      significantly related to smoking, shortness of breath, body mass index, and age,
      whereas restrictive defects were related to asbestosis, shortness of breath, and
      latency time. Chronic bronchitis increased with latency time in the three smoking
      groups and was significantly related to pleural thickening (OR 1.56 (1.00-2.42)).
      Shortness of breath was significantly associated with body mass index and pleural
      thickening (OR 1.30 (1.24-2.09)). CONCLUSIONS: Pleural thickening and asbestosis
      showed a significant association with latency time and exposure. FVC and FEV(1)
      decreased across increasing profusion with an added effect of pleural thickening.
      There was a significant and independent effect of exposure on lower levels of FVC
      and FEV(1). Obstructive defects were mainly related to smoking and restriction to
      asbestosis. Dust exposure and smoking were synergistic in increasing chronic
      bronchitis and shortness of breath report. Shortness of breath report was also
      related to pleural thickening and higher body mass index.

PMID- 11598971
TI  - Outdoor exposure to airborne polycyclic organic matter and adverse reproductive
      outcomes: a pilot study.
AB  - BACKGROUND: To investigate the association between outdoor airborne polycyclic
      organic matter (POM) and adverse reproductive outcomes in New Jersey, we used a
      cross-sectional design combining air quality data from the USA EPA Cumulative
      Exposure Project and individual data on pregnancy outcomes from birth and fetal
      death certificates at the census tract level. METHODS: After excluding plural
      births and chromosomal anomalies, 221,406 live births and 1,591 fetal deaths
      registered in New Jersey during the years of 1990 and 1991 were included. The
      exposure estimates were derived from modeled average POM concentrations for each
      census tract in the state. RESULTS: After adjustment for potential confounders,
      the odds ratios (OR) for very low birth weight for the highest exposure compared
      to the lowest exposure group was 1.31 (95% CI 1.15-1.51); among term births, high
      POM exposure was associated with low birth weight OR = 1.31 (95% CI 1.21-1.43),
      with fetal death OR = 1.19 (95% CI 1.02-1.39) and with premature birth OR = 1.25
      (95% CI 1.19-1.31). The univariate stratified analyses suggested effect
      modification of all observed associations by maternal alcohol consumption.
      CONCLUSIONS: This study found associations between outdoor exposure to modeled
      average airborne POM and several adverse pregnancy outcomes. The data and methods
      utilized in this pilot study may be useful for identifying hazardous air
      pollutants requiring in-depth investigation.

PMID- 11598972
TI  - Is testicular cancer an occupational disease of fire fighters?
AB  - BACKGROUND: A previous investigation showed an increased risk of testicular
      cancer among fire fighters in Wellington City, New Zealand, during the 1980s.
      Other studies of fire fighters had not identified testicular cancer as an
      occupational disease. METHODS: This was an historical cohort study of mortality
      and cancer incidence in all paid New Zealand fire fighters, from 1977 to 1995.
      RESULTS: The only cancer for which this study provided evidence of an increased
      risk was testicular cancer, even after excluding cases from the previous
      investigation. The standardized incidence ratio for 1990-96 was 3.0 (95%
      confidence interval: 1.3-5.90). There was no evidence that fire fighters were at
      increased risk from any particular cause of death. CONCLUSIONS: This study
      confirmed that New Zealand fire fighters are at increased risk of testicular
      cancer, although the reason is unknown. Other incidence studies of cancer in fire
      fighters are needed to confirm this finding.

PMID- 11598973
TI  - Meta-analysis of systemic sclerosis and exposure to solvents.
AB  - BACKGROUND: Although systemic sclerosis is a rare disease, incidence rates have
      increased recently in the United States. This study investigated the association
      between systemic sclerosis and exposure to solvents. METHODS: A Medline search of
      articles published between 1966 and 2000 dealing with solvent exposure and
      systemic sclerosis identified eight studies that met inclusion criteria of the
      meta-analysis. The studies included seven case-control studies and one cohort
      study published between 1989 and 1998. A series of meta-analyses of studies on
      systemic sclerosis and solvent exposure were performed for all studies and for
      case-control studies. A random effect model was used to calculate a combined
      estimator of relative risk. RESULTS: The combined estimator of relative risk for
      all studies was 2.91, with a 95% confidence interval (CI) of 1.60 to 5.30. The
      combined estimator of relative risk for the seven case-control studies was 3.14
      (95% CI, 1.56-6.33). CONCLUSIONS: A statistically significant increased relative
      risk for all studies and for case-control studies suggests that exposure to
      organic solvent may be a risk factor for developing systemic sclerosis. Further
      studies using other study designs and better control of confounders are needed.

PMID- 11598974
TI  - Factors associated with medical care-seeking due to low-back pain in scaffolders.
AB  - BACKGROUND: Few studies have demonstrated the consequences of having back pain
      and the mechanisms underlying decisions to seek medical care. This study aimed to
      assess the prevalence of back pain and other musculoskeletal complaints and to
      identify factors that determine specific type of care-seeking due to back pain
      among scaffolders. METHODS: A cross-sectional study was conducted among 323
      scaffolders. A questionnaire was used to collect data on musculoskeletal
      complaints and type of medical care sought. Logistic regression analysis was
      performed to study the risk factors for care-seeking for LBP, estimating
      Prevalence Ratios (PR) as a measure of association. RESULTS: The prevalence of
      musculoskeletal complaints was high. Severe back pain was reported by 28% of the
      scaffolders, LBP with sciatic pain by 23%, with sickness absence by 21%, with
      disability by 21%, and chronic back pain by 14%. Back pain was often accompanied
      by complaints of neck, shoulder, or knee. A general practitioner was sought by
      44% of the workers with LBP, a physiotherapist by 22%, an occupational physician
      by 20%, and a specialist by 11%. The nature and severity of back pain seemed to
      determine the decision to visit the GP. Irradiating pain and sickness absence
      were the strongest predictors for seeking medical care and being referred to a
      specialist or physiotherapist. CONCLUSION: The particular definition of back pain
      and the selection process of workers with LBP may partly determine the findings
      on work-related risk factors and health care utilization.

PMID- 11598976
TI  - Re: Lung cancer case-control study of beryllium workers. Sanderson WT, Ward EM,
      Steenland K, Petersen MR. Am. J. Ind. Med. 2001. 39:133-144.

PMID- 11598978
TI  - Advent of occupational health services research.
AB  - After lagging behind health services research in general health care, research is
      now examining health services provided to workers suffering occupational injuries
      and illnesses. The National Institute for Occupational Safety and Health, the
      Robert Wood Johnson Foundation Workers' Compensation Health Initiative, the
      Agency for Health Care Policy and Research (now the Agency for Healthcare
      Research and Quality), and the Canadian Institute for Work and Health co
      sponsored a June, 1999, conference to explore research needs in this area.
      Fundamental tenets for advancing occupational health services research include:
      adopting the goal of improving occupational health care, including better
      integration of preventive and curative care; creating standardized interstate
      occupational health care data sets that include medical, economic, and patient
      perspectives; better defining quality in occupational care and developing
      appropriate performance measures; in addition to medical costs, assessing social,
      economic, medical and functional outcomes of care; considering the connections
      between work and health, including general health services; and addressing the
      need to train qualified occupational health services researchers. Am. J. Ind.
      Med. 40:291-294, 2001. Published 2001 Wiley-Liss, Inc.

PMID- 11598979
TI  - Performance and quality measurement in occupational health services: current
      status and agenda for further research.
AB  - BACKGROUND: There is growing interest in evaluating the impact and effectiveness
      of occupational healthcare services (OHS). Managed care networks, case and
      disease management, worker health promotion, and utilization review services have
      proliferated in OHS, usually without scientifically based, objective measures of
      their impact on the quality of care, outcomes, or costs. Performance and quality
      improvement (QI) efforts in OHS are different from those in general health care
      because the population, range of conditions, setting of care, and primary
      outcomes of interest differ considerably. However, scientific knowledge resulting
      from the application of QI in general health care can provide a useful framework
      for the development of measures in OHS. METHODS: We describe the development,
      selection, and evaluation of OHS performance and quality measures, and propose a
      research agenda. CONCLUSIONS: Quality and performance measures in OHS should
      address common work-related conditions with high costs, suboptimal outcomes, or
      unclear parameters for ideal practices. They should reflect stakeholder
      priorities. Measures should be precise and quantifiable, clearly specified,
      reliable, valid, and sensitive to important changes. They should be based upon
      data that can be collected and analyzed at a reasonable cost and effort. The
      focus of measurement should be on situations where improvement can be achieved by
      those directly involved in OHS delivery, through defined approaches. Appropriate
      severity and case-mix adjustment may be especially problematic in OHS.
      Confidentiality, regulatory concerns, and appropriate use of results must be
      considered in the development and use of OHS measures. Research is needed to
      identify, develop, and validate OHS-specific measures, to establish risk
      adjustment methods, and to test the utility of this information in improving OHS.

PMID- 11598980
TI  - Integrating occupational health services and occupational prevention services.
AB  - BACKGROUND: Despite the human and monetary costs of occupational injury and
      illness, occupational health care has focused more on treatment than prevention,
      and prevention is not part of many clinical occupational health practices. This
      represents a failure of occupational health care to meet the health care needs of
      the working patients. METHODS: MEDLINE searches were conducted for literature on
      occupational medical treatment and the prevention of occupational injury and
      illness were reviewed to for linkages between prevention and treatment. Policy
      discussions which identify examples of programs that integrated prevention and
      treatment were included. RESULTS: Although examples of the integration of
      clinical and preventive occupational health services exist, there are challenges
      and barriers to such integration. These include inaction by clinicians who do not
      recognize their potential role in prevention; the absence of a relationship
      between the clinician and an employer willing to participate in prevention;
      economic disincentives against prevention; and the absence of tools that evaluate
      clinicians on their performance in prevention. CONCLUSIONS: Research is needed to
      improve and promote clinical occupational health preventive services.

PMID- 11598981
TI  - Creating safer and healthier workplaces: role of organizational factors and job
      characteristics.
AB  - BACKGROUND: A comprehensive understanding of workplace organizational risk
      factors for illness and injury and interventions to alleviate these factors is
      important for workplace prevention efforts. METHODS: We summarize the evidence
      for the role of workplace organizational factors and work factors in occupational
      health and safety (OHS). To the extent possible, we concentrate on factors at the
      level of the workplace, rather than the level of the individual. RESULTS: Three
      types of outcomes are considered: injuries, ill-health, and musculoskeletal
      problems; and we note the evidence for their relationship to work. We review
      workplace interventions intended to alleviate each type of outcome and note
      methodological limitations of previous research. CONCLUSIONS: Despite the
      methodological limitations, the balance of the literature supports the work
      relatedness of the three types of outcomes, although questions remain about exact
      mechanisms and the effectiveness of specific interventions. We discuss barriers
      to and incentives for creating safer and healthier workplaces.

PMID- 11598982
TI  - Relationship between health services outcomes and social and economic outcomes in
      workplace injury and disease: data sources and methods.
AB  - BACKGROUND: Understanding the mediating role of health care in mitigating social,
      economic and occupational role disability is a complex task. METHODS: No single
      method of research will be successful in addressing all elements of this NORA
      research priority area. In this paper, we argue that research methods are needed
      which have the following components: (1) the detailed measurement of therapeutic
      intervention and the impacts of this intervention on clinical and functional
      health status using study designs which rule out competing explanations, (2) a
      longitudinal follow-up component which measures social, economic, and
      occupational role function following the conclusion of therapy, and (3) a
      commitment to execute studies across multiple settings to observe the variations
      in health care and in social and occupational role function that arise as a
      result of differences in labor market factors and employer and government
      policies. CONCLUSIONS: More comprehensive portraits of the longitudinal
      trajectory of individual workers, social, economic and occupational role function
      following an occupational injury or illness will have significance for a large
      number of policy sectors.

PMID- 11598983
TI  - Natural rubber latex-related occupational asthma: association with interventions
      and glove changes over time.
AB  - BACKGROUND: Exposure to natural rubber latex (NRL) has been recognized as a cause
      of occupational asthma (OA), especially among health care workers (HCWs)
      associated with use of gloves. Little or no population-based data are available
      which chart the changes over time in the number of cases of OA as this problem
      was increasingly recognized and then interventions instituted. METHODS: We
      obtained the numbers of allowed asthma claims with exposure to latex by year in
      the province of Ontario, Canada from the Ontario Workplace Safety and Insurance
      Board; details of the cases from the largest teaching hospital were reviewed.
      Interventions included: (1) in 1996, the Board recommended in its focus for
      accommodation of sensitized workers, the reduction of aerosols of latex proteins
      and that hospital facilities use powder-free, low-protein or nonlatex gloves; and
      (2) hospitals instituted latex policies and glove changes at various dates. For
      example, at the largest teaching hospital, interventions included education and
      voluntary medical surveillance in 1994; substitution of low protein, "powder
      free" NRL gloves for non-sterile powdered gloves in 1995; and replacement of
      powdered sterile NRL gloves by lower protein, "powder-free" NRL gloves in 1997.
      RESULTS: Through 1999, there were 60 allowed claims for asthma in Ontario with
      exposure to latex; of these 49 (82%) were among HCWs. The number of claims among
      HCWs changed from 0 to 2 per year up to 1990; increased to 7 to 11 per year
      between 1991-1994; and declined to 3 per year in 1995-1996 and 1 to 2 per year in
      1997-1999. Of the ten institutions having two or more OA latex claims, all claims
      occurred in 1996 or earlier at 8 (80%). At the largest hospital, there were five
      accepted claims with year of diagnosis in 1993 (1 case), 1994 (3 cases), and 1995
      (1 case). CONCLUSIONS: These findings suggest that, despite the effect of
      increasing recognition, the introduction of gloves with reduced powder and/or
      protein, as well as other interventions have been associated temporally with
      declines in the number of cases of latex OA.

PMID- 11598984
TI  - Evaluation of a portable blood lead analyzer with occupationally exposed
      populations.
AB  - BACKGROUND: This project evaluated a portable electroanalytical instrument that
      is used to rapidly analyze blood lead levels in individuals, using a fresh whole
      blood sample (venous). METHODS: Samples were obtained from 208 lead-exposed
      employees who donated two 2 ml venous blood samples into "lead-free" evacuated
      tubes. One blood sample was analyzed onsite using the portable field instrument
      while the second sample was analyzed using graphite furnace atomic absorption
      spectrometry (GFAAS). RESULTS: According to GFAAS results, employee venous blood
      lead levels ranged from 1 microg/dl to 42 microg/dl. The mean difference between
      the results from the field instrument and GFAAS was less than 1 microg/dl.
      Analysis indicates that the results from the field instrument yielded a slight
      positive bias overall (P value = 0.0213), with less bias for blood lead levels
      above 10 microg/dl (P value = 0.0738). CONCLUSIONS: Within the blood range
      evaluated (1-42 microg/dl), the instrument performed adequately according to
      Clinical Laboratory Improvements Amendments (CLIA) proficiency requirements. The
      ability of the instrument to perform rapid analysis makes it potentially valuable
      to occupational health professionals for medical monitoring or on-site
      investigations.

PMID- 11598985
TI  - A historical cohort mortality study among shipyard workers in Genoa, Italy.
AB  - BACKGROUND: A historical cohort mortality study was conducted among 3984 shipyard
      workers assigned to ship repair, refitting, and construction in the harbor of
      Genoa, Italy, between 1960 and 1981. These workers were exposed to asbestos
      fibers, welding fumes and gases, silica dust, polycyclic aromatic hydrocarbons,
      and solvents. METHODS: Workers were classified in 20 different job-titles
      depending upon the type of activity. Standardized mortality ratios (SMRs) were
      computed using male residents of the Province of Genoa as the referent
      population. RESULTS AND CONCLUSIONS: For the whole cohort significantly increased
      SMRs were detected for all causes, all cancers, liver, larynx, lung, pleural and
      bladder cancers, respiratory tract diseases, and cirrhosis of the liver. The
      analysis by job-title showed increased SMRs not only for pleural cancer, but also
      for lung, laryngeal cancers and respiratory tract diseases in occupations
      entailing heavy asbestos exposure. Bladder and liver cancers and liver cirrhosis
      mortality also appeared to be related to occupational exposure.

PMID- 11598986
TI  - Malignant pleural mesothelioma in bakers and pastry cooks.
AB  - BACKGROUND: The occurrence of malignant pleural mesothelioma (MPM) among bakers
      and pastry cooks has never been documented. CASE REPORTS: We detected eight cases
      of MPM in bakers, pastry cooks, and biscuit cooks engaged in making,
      baking/cooking, and selling pastry/bread in two hospital-based series (Rome and
      Orbassano/Turin, Italy; period 1990-1997; 222 cases). Field-investigations
      revealed asbestos-containing material (ACM) in ovens for baking bread, that were
      manufactured prior to the 1980s. CONCLUSIONS: It is suggested that there is a
      possible new association of the risk of having worked as a baker or pastry cook
      and MPM. Presumptive source of exposure to asbestos was the use of asbestos
      insulated ovens.

PMID- 11598987
TI  - Psychosocial job factors and return-to-work after compensated low back injury: a
      disability phase-specific analysis.
AB  - BACKGROUND: Job characteristics may constitute a barrier to return-to-work (RTW)
      after compensated disabling low back pain (LBP). This study examines the impact
      of psychosocial job factors on time to RTW separately during the acute and
      subacute/chronic disability phases. METHODS: This is a retrospective cohort study
      of 433 LBP workers' compensation claimants with 1-4 years of follow-up. The
      association of psychosocial job factors with duration of work disability was
      estimated with Cox regression models, adjusting for injury history and severity,
      physical workload, and demographic and employment factors. RESULTS: High physical
      and psychological job demands and low supervisory support are each associated
      with about 20% lower RTW rates during all disability phases. High job control,
      especially control over work and rest periods, is associated with over 30% higher
      RTW rates, but only during the subacute/chronic disability phase starting 30 days
      after injury. Job satisfaction and coworker support are unrelated to time to RTW.
      CONCLUSIONS: Duration of work disability is associated with psychosocial job
      factors independent of injury severity and physical workload. The impact of these
      risk factors changes significantly over the course of disability.

PMID- 11598988
TI  - Response to: Mortality among rubber chemical manufacturing workers by M.M. Prince
      et al. Am. J. Ind. Med. 2000. 37: 590-598.

PMID- 11598990
TI  - Social and economic impacts of workplace illness and injury: current and future
      directions for research.

PMID- 11598991
TI  - The social consequences of occupational injuries and illnesses.
AB  - BACKGROUND: Most outcome studies of occupational injuries and illnesses have
      tended to focus on direct economic costs and duration of work disability. Rarely
      have the broader social consequences of work-related disorders or their impacts
      on injured workers' families, coworkers, and community been investigated. This
      paper examines a wide range of social consequences including workers'
      psychological and behavioral responses, vocational function, and family and
      community relationships. METHODS: Literature review and development of conceptual
      framework. RESULTS: Complex and multifactorial relationships are described
      whereby occupational injuries and illnesses produce a variety of social
      consequences involving filing and administration of workers' compensation
      insurance claims, medical care experiences, domestic function and activities of
      daily living, psychological and behavioral responses, stress, vocational
      function, rehabilitation and return to work, and equity and social justice.
      CONCLUSION: A research agenda is proposed for guiding future investigations in
      this field.

PMID- 11598992
TI  - Valuing the economic consequences of work injury and illness: a comparison of
      methods and findings.
AB  - BACKGROUND: Workplace injuries and fatalities in the US create significant
      economic costs to society. Although economic costs should measure the opportunity
      cost to society arising from injuries and fatalities, estimating them often
      proves difficult as a practical matter. This leads to a range of estimates for
      valuing these costs. METHODS: This paper compares methods of economic valuation,
      focusing in particular on how different methods diverge to varying degrees from
      measuring the "true" economic costs of injuries and illnesses. In so doing, it
      surveys the literature that has arisen in the past 25 years to measure different
      aspects of economic consequences. RESULTS: Estimates of the costs of injuries and
      fatalities tend to understate the true economic costs from a social welfare
      perspective, particularly in how they account for occupational fatalities and
      losses arising from work disabilities. CONCLUSION: Although data availability
      often makes estimation of social welfare costs difficult, researchers should
      attempt to more fully integrate such approaches into estimation procedures and
      interpretation of their results.

PMID- 11598993
TI  - Quantifying social consequences of occupational injuries and illnesses: state of
      the art and research agenda.
AB  - BACKGROUND: Quantitative methods for describing the social effects of
      occupational injury and illness are evaluated including surveys of prevalence and
      ratings of severity of social role disability. METHODS: The reliability and
      validity for the injured worker population of the most commonly used general and
      condition-specific role disability measures is reviewed and summarized. This
      review is used to support the development of a prototype strategy for quantifying
      the social consequences of occupational injuries and to identify areas of need
      for further research and development. CONCLUSIONS: Research is needed to: (a)
      determine which of existing measures is most precise in describing the severity
      of dysfunction due to a specific illness or injury, (b) expand the development of
      measures of specific role functioning (including paid work), and (c) develop item
      banks to support the construction of computer adaptive assessments of role
      functioning.

PMID- 11598994
TI  - New methods and data sources for measuring economic consequences of workplace
      injuries.
AB  - BACKGROUND: Evaluation of programs and policies to reduce the incidence of
      workplace injuries require that the consequences of injury are estimated
      correctly. Because workplace injuries are complex events, the availability of
      data that reflects this complexity is the largest obstacle to this estimation.
      METHODS: We review the literature on the consequences of workplace injuries for
      both workers and employers, focusing on data sources, particularly linked
      administrative data from different public agencies. We also review other
      approaches to obtaining data to examine workplace injuries, including public-use
      longitudinal survey data, primary data collection, and linked employee-employer
      databases. We make suggestions for future research. RESULTS: Recent advances in
      the literature on the economic consequences of workplace injuries for workers
      have been driven to a great extent by the availability of new data sources. Much
      remains unexplored. We find longitudinal survey databases including the National
      Longitudinal Survey of Youth, and the Health and Retirement Survey, to be very
      promising though largely untapped sources of data on workplace injuries. We also
      find that linked employee-employer databases are well suited for the study of
      consequences for employers. CONCLUSIONS: We expect that new data sources should
      lead to rapid advances in our understanding of the economic consequences of
      workplace injuries for both workers and employers.

PMID- 11598995
TI  - Determinants of duration of disability and return-to-work after work-related
      injury and illness: challenges for future research.
AB  - BACKGROUND: The purpose of this review was to identify critical data and research
      needs in addressing the following question: What are the primary factors that
      affect the time lost from work, return-to-work (RTW), subsequent unemployment,
      and changes in occupation after disabling illness or injury? METHODS: Review of
      the literature to identify research challenges originating from the multitude of
      disciplines, data sources, outcome measures, and methodological and analytical
      problems. RESULTS: About 100 different determinants of RTW outcomes were
      identified. Their impact varies across different phases of the disablement
      process. Recommendations are provided for addressing five selected research
      challenges. CONCLUSION: Interdisciplinary research needs to develop a
      comprehensive conceptual framework. Priority should be given to studies on
      specific domains of risk factors meeting five selection criteria: amenability to
      change; relevance to users of research; generalizability across health
      conditions, disability phases, and settings; "degree of promise" as derived from
      qualitative exploratory studies; and capacity to improve measurement instruments.
      Combining qualitative and quantitative research methods is necessary to bridge
      existing knowledge gaps.

PMID- 11598996
TI  - Regulation of olfactory neurogenesis by amidated neuropeptides.
AB  - The existence of stem cells in the CNS raises issues concerning the ability of
      nervous tissues to regenerate in the adult mammal and provides new perspectives
      on the treatment of degenerative disease and traumatic injury of the nervous
      system. These cells have a relatively limited range of locations within the
      nervous system and include cells of the rostral migratory stream, hippocampus,
      retina, and olfactory epithelium. The olfactory epithelium has been studied as a
      model of adult neuronal regeneration, with neuronal precursor/basal cells serving
      as the olfactory "stem cells." The identification of factors that promote
      neuronal proliferation or regeneration within the olfactory epithelium can
      provide clues to the process of adult mammalian nervous system repair and
      treatment. Multiple factors have been examined that appear to influence the
      proliferation and subsequent maturation of basal cells. These factors include
      nerve growth factor, fibroblast growth factor-2, epidermal growth factor, and
      insulin/insulin-like growth factor-1. Recently, two amidated neuropeptides,
      neuropeptide Y (NPY) and pituitary adenylate cyclase-activating polypeptide
      (PACAP38), identified in the olfactory epithelium have been shown to promote
      dramatically neuronal proliferation. The effects of NPY and PACAP suggest that
      amidated neuropeptides may serve a broad developmental and regenerative role in
      the mammalian olfactory epithelium.

PMID- 11598997
TI  - A subpopulation of nervus terminalis neurons projects to the olfactory mucosa in
      Xenopus laevis.
AB  - Biocytin application to the normal or zinc sulfate-treated nasal cavity of
      Xenopus laevis was used to trace retrogradely neurons associated with the
      terminal nerve (TN). Immunocytochemistry was conducted to identify the
      relationship of gonadotropin-releasing hormone-immunoreactive (GnRH-ir) TN
      neurons with biocytin-labeled neurons. Neurons that accumulated biocytin were
      located in olfactory nerve fascicles close to the olfactory mucosa lining the
      caudal, medial, and rostral walls of the principal cavity. GnRH-ir fibers were
      observed only in the olfactory nerve fascicle projecting to the rostral edge of
      the principal cavity. In addition, GnRH-ir fibers did not contact biocytin
      labeled TN neurons. We hypothesize that these two classes of neurons represent
      separate components of the TN.

PMID- 11598998
TI  - Axon-Schwann cell interactions regulate the expression of fibroblast growth
      factor-5 (FGF-5).
AB  - We screened for genes whose expression is significantly up- or downregulated
      during Wallerian degeneration in adult rat sciatic nerve with cDNA arrays.
      Fibroblast growth factor-5 (FGF-5) mRNA seemed to be induced. This was confirmed
      by northern blotting and in situ hybridization, as well as Western blotting for
      FGF-5 in axotomized nerve. Axon-Schwann cell interactions decreased the steady
      state level of FGF-5 mRNA in regenerating sciatic nerves, and forskolin
      diminished its expression in cultured Schwann cells. We conclude that denervated
      Schwann cells synthesize FGF-5, which is a secreted, neuronotrophic member of the
      FGF family.

PMID- 11598999
TI  - Altered gene expression in Schwann cells of connexin32 knockout animals.
AB  - The discovery that the dominant X-linked form of Charcot-Marie-Tooth disease
      (CMTX), a genetic disease of the peripheral nervous system (PNS), is associated
      with mutations in connexin32 (Cx32) has brought attention to the importance of
      connexins in glial cell biology. To gain further insight into the consequences of
      Cx32 deficiency, we have undertaken a detailed characterization of the gene
      expression profile of Schwann cells isolated from the sciatic nerve of wild-type
      and Cx32-null mice. Schwann cells exhibit two distinct phenotypes, myelinating
      and nonmyelinating, which are defined by their different morphology with respect
      to axons and by their unique profile of gene expression. Our findings show that,
      regardless of the mouse genotype, cultured Schwann cells express similar levels
      of messages for a number of connexins and for genes characteristic of both the
      myelinating and the nonmyelinating phenotypes. Furthermore, we have identified
      Cx36, a member of the gamma subclass of connexins, which are preferentially
      expressed in neuronal cells of mouse brain and retina, as an additional connexin
      present in Schwann cells. Mice lacking Cx32, however, exhibited a marked up
      regulation of glial fibrillary acidic protein (GFAP), a cytoskeletal protein
      usually synthesized only by nonmyelinating Schwann cells. This observation was
      extended to the PNS in vivo and did not reflect a general perturbation of the
      expression of other nonmyelinating Schwann cell genes. These findings demonstrate
      that the absence of Cx32 results in a distinct pattern of gene dysregulation in
      Schwann cells and that Schwann cell homeostasis is critically dependent on the
      correct expression of Cx32 and not just any connexin. Identifying the
      relationship between increased GFAP expression and the absence of Cx32 could lead
      to the definition of specific roles for Cx32 in the control of myelin homeostasis
      and in the development of CMTX.

PMID- 11599000
TI  - Effect of cyclic AMP on the expression of myelin basic protein species and myelin
      proteolipid protein in committed oligodendrocytes: differential involvement of
      the transcription factor CREB.
AB  - Our previous results support the idea that CREB (cyclic AMP-response element
      binding protein) may be a mediator of neuroligand and growth factor signals that,
      coupled to different signal transduction pathways, play different roles at
      specific stages of oligodendrocyte development. In the early stages, when cells
      are immature precursors, CREB may play a role as a mediator of protein kinase C
      (PKC)/mitogen-activated protein kinase (MAPK) pathways regulating cell
      proliferation. In contrast, at a later stage, when cells are already committed
      oligodendrocytes, CREB seems to play an important role as a mediator in the
      stimulation of myelin basic protein (MBP) expression by cyclic AMP (cAMP). In
      this study, we have investigated whether cAMP and CREB play a role in regulating
      the expression of all or on the other hand particular MBP isoforms. The results
      indicated that treatment of committed oligodendrocytes with the cAMP analogue db
      cAMP results in a pattern of expression of MBP-related polypeptides that most
      closely resembles the pattern of MBPs observed in cerebra from adult animals.
      Experiments in which CREB expression was inhibited using a CREB antisense
      oligonucleotide, suggested that CREB is involved in the cAMP-dependent
      stimulation of all the MBP isoforms. In contrast, we have found that db-cAMP
      stimulates the expression of myelin proteolipid protein (PLP) in a process that
      occurs despite inhibition of CREB expression. These results support the idea that
      cAMP stimulates the maturation of oligodendrocytes and stress the fact multiple
      mechanisms may convey the action of this second messenger modulating
      oligodendrocyte differentiation and myelination.

PMID- 11599001
TI  - Disturbed oligodendrocyte development and recovery from hypomyelination in a c
      myc transgenic mouse mutant.
AB  - The complexity of interactions underlying the elaboration of myelin has been
      extensively demonstrated. We provide evidence that signals promoting myelination
      are not confined to the normal developmental time window for myelination and
      persist well into adult life. The 2-50 mutant, described previously, carries a c
      myc transgene regulated by a myelin basic protein promoter. This mutant is
      characterised by severe hypomyelination and abnormal oligodendrocytes in early
      life, followed by loss of the phenotype and normal longevity. We show that c-myc
      expression in early oligodendrocyte development results in a substantial
      reduction of cells of this lineage. However, apparent complete recovery,
      associated with loss of c-myc expression, axonal survival, and gradual myelin
      accumulation, is observed by 4 months of age. Thus, stimulation of myelination
      continues during adult life until normal myelin levels are established. We
      propose that this mutant may contribute to the characterisation of
      oligodendrocyte responses to myelinating signals.

PMID- 11599003
TI  - Transformation of donor-derived bone marrow precursors into host microglia during
      autoimmune CNS inflammation and during the retrograde response to axotomy.
AB  - Macrophages in the brain can have a triple source. They may originate from
      recently blood-derived precursors, from the largely resident perivascular cell
      population (perivascular macrophages and related cells), and from intrinsic
      parenchymal as well as perivascular microglia. Although continuous exchange of
      part of the perivascular cell population with bone marrow-derived precursors is
      now accepted, the turnover of adult parenchymal microglia has remained enigmatic.
      Using bone-marrow chimeras carrying an unexpressed marker gene and carbon
      labeling of peripheral monocyte/macrophages in a combined model of facial nerve
      axotomy and transfer experimental autoimmune encephalitis, we demonstrate for the
      first time that there is an easy to induce exchange between parenchymal central
      nervous system (CNS) microglia and the macrophage precursor cell pool of the bone
      marrow. Furthermore, very low level infiltration of the CNS parenchyma by
      recently bone marrow-derived microglia could be observed after simple peripheral
      nerve axotomy that is followed by neuronal regeneration. Thus, microglial cells
      can be considered wanderers between the peripheral immune system and the CNS
      where they may act as a "Trojan horse" in infections. The fact that recently bone
      marrow-derived parenchymal microglia fully integrate into a regenerating brain
      nucleus' architecture encourages entirely new approaches for delivering genes
      into the adult CNS.

PMID- 11599002
TI  - Expression of small heat shock proteins and intermediate filaments in the human
      optic nerve head astrocytes exposed to elevated hydrostatic pressure in vitro.
AB  - The small heat shock proteins (sHSP), alpha B-crystallin and Hsp27 are chaperone
      molecules that maintain the integrity of intermediate filament (IF) network and
      prevent unfolding of cellular proteins induced by stress. In the optic nerve head
      (ONH) of eyes with glaucoma, reactive astrocytes expressed Hsp27, perhaps in
      response to stress related to elevated intraocular pressure. In this study, we
      determined the effect of elevated hydrostatic pressure (HP) in the synthesis,
      distribution and co-localization of alpha B-crystallin and Hsp27 with IF in
      cultured ONH astrocytes. Astrocyte monolayers were pressurized to 60 mm Hg (92%
      air 8% CO(2)) and incubated at 37 degrees C for 6, 24 or 48 hr. Controls were
      exposed to ambient pressure. Cells were analyzed by immunocytochemistry, Western
      blot and immunoprecipitation using antibodies to Hsp27, alpha B-crystallin,
      vimentin or GFAP. Control astrocytes seemed flat, polygonal with short processes.
      alpha B-crystallin appeared granular in the perinuclear area and filamentous in
      the cell periphery. Fine granular Hsp27 was distributed throughout the cytoplasm.
      GFAP and vimentin co-localized with Hsp27 in the cytoplasm. Astrocytes exposed to
      HP were star-shaped with long processes. Hsp27 was condensed in large granules
      around the nucleus. GFAP and vimentin co-localized with Hsp27 and alpha B
      crystallin in the perinuclear area. Western blot and metabolic labeling detected
      increased synthesis of Hsp27, GFAP and vimentin but no change in alpha B
      crystallin. These results indicated that GFAP and vimentin associate with Hsp27
      and alpha B-crystallin in ONH astrocytes. HP affected the integrity of the
      cytoskeleton consistent with morphological changes. Small HSP may reinforce and
      maintain IF integrity in response to HP.

PMID- 11599004
TI  - Differential regulation of p75 and trkB mRNA expression after depolarizing
      stimuli or BDNF treatment in basal forebrain neuron cultures.
AB  - Extensive evidence suggests that BDNF regulates neural function and architecture
      after depolarization. Expression of BDNF is increased after depolarization, and
      the ability of BDNF to modulate synaptic function is well documented. To further
      investigate BDNF signaling after activity, we analyzed the effects of
      depolarization or BDNF treatment on receptor mRNA expression in cultured basal
      forebrain neurons. Levels of mRNA coding for the cognate BDNF receptor, trkB, as
      well as the common neurotrophin receptor, p75, were quantitated simultaneously
      using a sensitive solution hybridization technique. Depolarization or BDNF
      treatment increased p75 mRNA expression 94% and 195%, respectively. In contrast,
      trkB message decreased 23% after depolarization but was unchanged by BDNF
      treatment. Together, these changes resulted in significant increases in the
      p75/trkB ratio after depolarization or BDNF treatment that could alter BDNF
      binding or signal transduction.

PMID- 11599005
TI  - Glutamate transporter EAAC1 is expressed on Muller cells of lower vertebrate
      retinas.
AB  - The expression of glutamate transporter EAAC1 was investigated in carp and
      bullfrog retinas using Western blotting, immunofluorescence double labeling and
      confocal laser scanning microscopic techniques. In addition to a variety of
      retinal neurons, radially oriented elements spanning the whole neural retinas of
      carp and bullfrog were also EAAC1-immunoreactive, and EAAC1 was found to be
      predominantly on the cell membrane. Virtually all EAAC1-labeled radial elements
      were immunopositive to glial fibrillary acidic protein (GFAP), a specific marker
      for retinal Muller cells of carp and bullfrog, indicating that they were Muller
      cells. This finding suggests that EAAC1, which has been thought to be an
      exclusively neuronal type, may be a glial transporter as well. EAAC1 of Muller
      cells may play an important modulatory role in the retina by making contributions
      to glutamate homeostasis.

PMID- 11599006
TI  - Brain-derived neurotrophic factor triggers a rapid glutamate release through
      increase of intracellular Ca(2+) and Na(+) in cultured cerebellar neurons.
AB  - We reported previously that BDNF induced glutamate release was dependent on
      intracellular Ca(2+) but not extracellular Ca(2+) in cerebellar neurons (Numakawa
      et al., 1999). It was revealed that the release was through a non-exocytotic
      pathway (Takei et al., 1998; Numakawa et al., 1999). In the present study, we
      monitored the dynamics of intracellular Ca(2+) and Na(+) in cerebellar neurons,
      and investigated the possibility of reverse transport of glutamate mediated by
      BDNF. As reported, BDNF increased the intracellular Ca(2+) level. We found that
      the Ca(2+) increase induced by BDNF was completely blocked by xestospongin C, an
      IP(3) receptor antagonist, and U-73122, a PLC-gamma inhibitor. Xestospongin C and
      U-73122 also blocked the BDNF-dependent glutamate release, suggesting that the
      BDNF-induced transient increase of Ca(2+) through the activation of the PLC
      gamma/ IP(3) pathway was essential for the glutamate release. We found that BDNF
      induced a Na(+) influx. This was blocked by treatment with TTX. U-73122 and
      xestospongin C blocked the BDNF-induced Na(+) influx, suggesting that the
      Na(+)influx required the BDNF-induced Ca(2+) increase. Next, we examined the
      possibility that a co-transporter of Na(+) and glutamate was involved in the BDNF
      induced glutamate release. BDNF-induced glutamate release was blocked by L-trans
      pyrollidine-2,4-dicalboxylic acid (t-PDC), a glutamate transporter inhibitor,
      whereas neither the 4-aminopyridine (4AP)- nor high potassium (HK(+))-induced
      release was blocked by t-PDC. In addition, DL-threo-beta-benzyloxyaspartate (DL
      TBOA) also blocked the BDNF-mediated glutamate release, suggesting that reverse
      transport of glutamate may be involved. All the results therefore suggest that
      Na(+)-dependent reverse transport contributes to BDNF-mediated transmitter
      release through the PLC-gamma/IP(3)-mediated Ca(2+) signaling.

PMID- 11599007
TI  - Excitation of the pedunculopontine tegmental NMDA receptors induces wakefulness
      and cortical activation in the rat.
AB  - Microinjection of the excitatory amino acid, L-glutamate into the brainstem
      pedunculo pontine tegmentum (PPT) has been shown to induce wakefulness, however,
      it has been unclear that receptors mediate this effect. The aim of this study was
      to test the hypothesis that in the PPT, L-glutamate induces cortical activation
      and wakefulness via activation of NMDA receptors. To test this hypothesis, three
      sets of micro-injections into the PPT were carried out on two different groups of
      rats that were then allowed to move freely although chronic instrumentation
      recorded sleep/wake states. Three days after the initial control injections of
      saline, in a contra-lateral site, Group I was micro-injected with saline +
      glutamate (saline first, and glutamate 15 min later); after another 3 days, the
      same rats were micro-injected with the NMDA-receptor-specific antagonist, 2-amino
      5-phosphonopentanoic acid, (AP5) + glutamate. Group II received the same initial
      control injections (saline only), then AP5 + glutamate and the saline + glutamate
      micro-injections last. In rats that were not pretreated with AP5, microinjection
      of a 90 ng dose of L-glutamate (0.48 nmol in a volume of 0.1 microl vehicle) kept
      animals awake for 2-3 hr by eliminating both slow-wave sleep (SWS) and rapid eye
      movement (REM) sleep. These behavioral state changes were accompanied by
      concomitant increase in the power of gamma (gamma) frequency (20-60 Hz) waves in
      the cortical EEG. Pretreatment of L-glutamate injection sites with 0.48 nmol of
      AP5 blocked L-glutamate-induced-wakefulness and preserved a normal amount of
      wakefulness and sleep. Pretreatment with AP5 decreased the power of gamma-wave
      activity below its control level. These results support the hypothesis that the
      glutamate-induced-wakefulness and cortical activation effects are mediated via
      the NMDA receptors.

PMID- 11599008
TI  - Cholinergic modulation of synaptic physiology in deep layer entorhinal cortex of
      the rat.
AB  - We have recently shown that cholinergic effects on synaptic transmission and
      plasticity in the superficial (II/III) layers of the rat medial entorhinal cortex
      (EC) are similar, but not identical, to those in the hippocampus (Yun et al.
      [2000] Neuroscience 97:671-676). Because the superficial and deep layers of the
      EC preferentially convey afferent and efferent hippocampal projections,
      respectively, it is of interest to compare cholinergic effects between the two
      regions. We therefore investigated the physiological effects of cholinergic
      agents in the layer V of medial EC slices under experimental conditions identical
      to those in the previous study. Bath application of carbachol (0.5 microM)
      induced transient depression of field potential responses in all cases tested (30
      of 30; 18.5% +/- 2.3%) and rarely induced long-lasting potentiation (only 3 of
      30; 20.4% +/- 3.2% in successful cases). At 5 microM, carbachol induced transient
      depression only (20 of 20, 48.9% +/- 2.8%), which was blocked by atropine (10
      microM). Paired-pulse facilitation was enhanced during carbachol-induced
      depression, suggesting presynaptic action of carbachol. Long-term potentiation
      (LTP) could be induced in the presence of 10 microM atropine by theta burst
      stimulation, but its magnitude was significantly lower (9.1% +/- 4.7%, n = 15)
      compared to LTP in control slices (22.4% +/- 3.9%, n = 20). These results,
      combined with our previous findings, demonstrate remarkably similar cholinergic
      modulation of synaptic transmission and plasticity across the superficial and
      deep layers of EC.

PMID- 11599009
TI  - Caspase cleavage of exon 9 deleted presenilin-1 is an early event in apoptosis
      induced by calcium ionophore A 23187 in SH-SY5Y neuroblastoma cells.
AB  - Presenilins (PSs) are mutated in a majority of familial Alzheimer disease (FAD)
      cases. Mutated PSs may cause FAD by a number of pro-apoptotic mechanisms, or by
      regulating gamma-secretase activity, a protease involved in beta-amyloid
      precursor protein processing to the neurotoxic beta-amyloid peptide. Besides
      their normal endoproteolytic processing, PSs are substrates for caspases, being
      cleaved to alternative N-terminal and C-terminal fragments. So far little is
      known about the role of PSs cleavage in the apoptotic machinery. Here, we used SH
      SY5Y neuroblastoma cells stably transfected with wild-type or exon 9 deleted
      presenilin 1 (PS1) in a time-course study after the exposure to the calcium
      ionophore A23187. During and after exposure to A 23187, intracellular calcium
      levels were higher in exon 9 deleted PS1 cells as compared with non-transfected
      and wild-type PS1 transfected cells. Cell death and the enrichment of apoptotic
      cells after A23187 exposure were increased by overexpression of exon 9 deleted
      PS1 as compared with the control cell lines. Wild-type PS1 cells were compared
      with exon 9 deleted PS1 cells and the temporal relationship between PS1 and other
      caspase substrates cleavages was analyzed. Exon 9 deleted PS1 cells exhibited a
      higher caspase-3 activation and a greater cleavage of PS1 and poly(ADP-ribose)
      polymerase (PARP) compared with wild-type PS1 cells. Exon 9 deleted PS1 cleavage
      occurred earlier than other caspase substrate cleavages (i.e., PARP and
      gelsolin), simultaneous with minimum detectable caspase-3 activation. Therefore,
      alternative cleavage of PS1 may play an important role for the regulation of the
      proteolytic cascade activated during apoptosis.

PMID- 11599010
TI  - Antioxidant compounds and Ca(2+) pathway blockers differentially protect against
      methylmercury and mercuric chloride neurotoxicity.
AB  - The effects of the environmental contaminants methylmercury (MeHg) and inorganic
      mercury (HgCl(2)) on cell viability, intracellular calcium concentration
      ([Ca(2+)](i)), and reactive oxygen species (ROS) generation were studied in rat
      cerebellar granule neuron cultures using fluorescent methods. MeHg exhibited an
      LC(50) (2.47 microM) tenfold lower than that of HgCl(2) (26.40 microM). To study
      the involvement of oxidative stress and Ca(2+) homeostasis disruption in mercury
      induced cytotoxicity, we tested the neuroprotective effects of several agents
      that selectively interfere with these mechanisms. After a 24 hr exposure, the
      cytotoxic effect of both mercury compounds was reduced by thapsigargin, an
      inhibitor of endoplasmic reticulum Ca(2+)-ATPase; the Ca(2+) channel blocker
      flunarizine; and the Na(+)/Ca(2+) exchanger blocker benzamil. All these compounds
      decreased the mercury-mediated [Ca(2+)](i) rise. These results indicate that
      Ca(2+) influx through Ca(2+) channels and the Na(+)/Ca(2+) exchanger and Ca(2+)
      mobilization from the endoplasmic reticulum are involved in mercury-mediated
      cytotoxicity. The antioxidants probucol and propyl gallate reduced the HgCl(2)
      toxicity. Probucol and vitamin E partially inhibited the MeHg toxicity after a 24
      hr period, whereas propyl gallate completely prevented this effect. Probucol
      slightly reduced ROS generation in methylmercury-exposed cultures and decreased
      mercury-mediated rise of [Ca(2+)](i). Propyl gallate abolished ROS generation and
      partially inhibited the increase of [Ca(2+)](i) induced by both mercury
      compounds. Propyl gallate also protected human cerebral cortical neuron cultures
      from the MeHg effect even after 72 hr of MeHg exposure, thus showing a long
      lasting effect. Our data suggest that disruption of redox equilibrium and Ca(2+)
      homeostasis contribute equally to HgCl(2)-mediated toxicity, whereas oxidative
      stress is the main cause of MeHg neurotoxicity.

PMID- 11599011
TI  - Comparative anatomy of excretory organs in vestimentiferan tube worms
      (Pogonophora, Obturata).
AB  - In the past, the excretory systems of only few vestimentiferan species have been
      examined in detail. This study presents comparative data on eight species on the
      basis of histological serial sections. Ridgeia piscesae was studied by
      transmission electron microscopy. All species examined possess a central
      excretory organ consisting of numerous small branching and intertwined excretory
      tubules. These are connected to voluminous glandular excretory ducts that lead to
      the exterior by single or paired excretory pores located at the anterior end of
      the vestimentum. A comparative analysis shows differences among the species with
      regard to several features, such as the number of excretory pores,
      presence/absence of excretory grooves and papillae, position of the excretory
      organ relative to the brain, and the shape of the excretory ducts. Neither
      podocytes nor coelomoducts could be detected; therefore, there is no indication
      of the presence of metanephridia. The vestimentiferan excretory system shows some
      similarities with the design in Athecanephria (Pogonophora, Perviata) and a
      general resemblance to the design in sabellid polychaetes, even though in the
      latter metanephridia are clearly present.

PMID- 11599012
TI  - Biomechanical scaling of the hominoid mandibular symphysis.
AB  - Experimental investigation of mandibular bone strain in cercopithecine primates
      has established that the mandible is bent in the transverse plane during the
      power stroke of mastication. Additional comparative work also supports the
      assumption that the morphology of the mandibular symphysis is functionally linked
      to the biomechanics of lateral transverse bending, or "wishboning" of the
      mandibular corpus. There are currently no experimental data to verify that
      lateral transverse bending constitutes an important loading regime among hominoid
      primates. There are, however, allometric models from cercopithecoid primates that
      allow prediction of scaling patterns in hominoid mandibular dimensions that would
      be consistent with a mechanical environment that includes wishboning as a
      significant component. This study uses computed tomography (CT) scans to
      visualize cortical bone distribution in the anterior corpus of a sample of four
      genera of extant hominoids. From the cortical bone contours, area properties of
      the mandibular symphysis are calculated, and these variables are subjected to an
      allometric analysis to detect whether scaling of jaw dimensions are consistent
      with a wishboning loading regime. Scaling of the hominoid symphysis recalls
      patterns observed in cercopithecoid monkeys, which lends indirect support for the
      hypothesis that wishboning is an integral part of the masticatory loading
      environment in living apes. Inclination of the symphysis, rather than changes in
      cross-sectional shape or development of the superior transverse torus, represents
      a morphological solution for minimizing the potentially harmful effects of
      wishboning in the jaws of these primates.

PMID- 11599013
TI  - Shape changes and growth trajectories in the early stages of three species of the
      genus Diplodus (Perciformes, Sparidae).
AB  - The larvae of three species of the genus Diplodus (Diplodus vulgaris, D. sargus,
      and D. puntazzo) colonize shallow waters along the Mediterranean coasts and,
      after a short period spent in the water column, they settle. For all three
      species this habitat transition is characterized by important shape changes
      mostly related to swimming capacity and feeding behavior. In this study,
      geometric morphometrics are used to characterize shape changes during the early
      juvenile life of specimens collected in a single locality in order to compare
      growth curves and allometric relationships. Size-related shape changes proved to
      be similar for all three species and are consistent with the ecological
      transition. A nonparametric smoothing technique (Loess) was used to fit the
      scatter of shape on size. The graphical representation (of most size-related
      shape variability) of this fitting technique shows how major shape changes are
      rapid for small sizes and slow down successively. The approach allows for the
      visualization of allometry and the fitting technique might help in defining the
      allometric growth pattern, thus contributing to the study of the autoecology of
      the species and in establishing terms for comparison with other ecologically or
      phylogenetically related species.

PMID- 11599014
TI  - Anatomy and histology of the brain and sense organs of the Antarctic eel cod
      Muraenolepis microps (Gadiformes; Muraenolepididae).
AB  - Brain regions, cranial nerves, and sense organs in Muraenolepis microps, an
      Antarctic gadiform fish, were examined to determine which features could be
      attributed to a gadiform ancestry and which to habitation of Antarctic waters. We
      found that the central nervous system and sense organs are well developed,
      showing neither substantial regression nor hypertrophy. A detailed drawing of the
      brain and cranial nerves is provided. The rostral position of the olfactory bulbs
      and telencephalic size and lobation are common for the order. The optic tectum
      and corpus cerebelli are smaller than in most other gadiforms. The shape of the
      corpus cerebelli is not distinctive among gadiforms. The lateral line region is
      moderately well-developed, but not hypertrophied to the extent seen in deep-sea
      gadiforms. As is the case in gadids possessing barbels and elongated pelvic rays,
      Muraenolepis has well-developed facial lobes, although these are smaller and more
      laterally positioned. The vagal lobes are deeply placed in the rhombencephalon
      and project into the fourth ventricle. The brain of Muraenolepis resembles that
      of a phyletically derived gadoid, especially a phycid, more than it resembles the
      brain of a phyletically basal macrourid. Two histological features of the
      diencephalon of Muraenolepis appear to be unique among gadiforms: a well
      organized thalamic central medial nucleus and subependymal expansions.
      Muraenolepis has a pure rod retina like many deep-sea species but lacks the
      superimposed layers of rod outer segments. The histology of the nonvisual sense
      organs, especially the olfactory and external taste systems, are well-developed
      in Muraenolepis but not hypertrophied. We relate our findings to what is known
      about neural morphology in other gadiforms and in phyletically distant
      notothenioids and liparids that are sympatric with Muraenolepis on the Antarctic
      shelf. The only feature that reflects an Antarctic existence is the diencephalic
      subependymal expansions, which within notothenioids mirror the habitation of cold
      waters and have been found in every Antarctic species examined to date. Although
      the waters of the Antarctic shelf are cold, dark, and deep, brain and sense organ
      morphology in Muraenolepis are remarkably free of extreme specialization.

PMID- 11599015
TI  - The morphological basis of hallucal orientation in extant birds.
AB  - The perching foot of living birds is commonly characterized by a reversed or
      opposable digit I (hallux). Primitively, the hallux of nonavian theropod
      dinosaurs was unreversed and lay parallel to digits II-IV. Among basal birds, a
      unique digital innovation evolved in which the hallux opposes digits II-IV. This
      digital configuration is critical for grasping and perching. I studied skeletons
      of modern birds with a range of hallucal designs, from unreversed (anteromedially
      directed) to fully reversed (posteriorly directed). Two primary correlates of
      hallucal orientation were revealed. First, the fossa into which metatarsal I
      articulates is oriented slightly more posteriorly on the tarsometatarsus,
      rotating the digit as a unit. Second, metatarsal I exhibits a distinctive torsion
      of its distal shaft relative to its proximal articulation with the
      tarsometatarsus, reorienting the distal condyles and phalanges of digit I.
      Herein, I present a method that facilitates the re-evaluation of hallucal
      orientation in fossil avians based on morphology alone. This method also avoids
      potential misinterpretations of hallucal orientation in fossil birds that could
      result from preserved appearance alone.

PMID- 11599016
TI  - Histological study of Goniodoris castanea Alder and Hancock, 1845 (Nudibranchia,
      Doridoidea, Goniodorididae).
AB  - The major organ systems of Goniodoris castanea were investigated by histological
      means, with an emphasis on those structures that are difficult to see by
      dissection. The species is characterized by some peculiar features that are
      unique or seldom within the Nudibranchia, such as the complete absence of
      specialized vacuolated cells, the presence of globular salivary glands, the
      presence of cuticular structures in the proximal intestine, a muscular sphincter
      around the distal vaginal duct, and the position of the blood gland closer to the
      pericardium than to the nervous system. Some of these characters are discussed in
      a phylogenetic context, although a thorough phylogenetic analysis is preliminary,
      due to lack of knowledge of probably related species.

PMID- 11599017
TI  - Development of segments and appendages in embryos of the desert scorpion
      Paruroctonus mesaensis (Scorpiones: Vaejovidae).
AB  - The scanning electron microscope was used to study the changing features of
      scorpion embryos from the blastula through early stages in the development of
      appendages. The earliest scorpion fossils (Silurian period) have structures more
      advanced than the embryos herein, so the possibility is considered that these
      embryos still retain and display some features indicative of evolutionary
      patterns in adult pre-Silurian ancestors. The blastodisc stage is followed by a
      knob-like germinal center that gives rise to most of the embryo body. The
      germinal center elongates on the ventral surface of the spherical yolk mass. The
      broad cephalic lobe is first delineated from the following pedipalpal segment.
      The limbbuds for the pedipalps and anterior walking legs appear, as additional
      segments are added at a growth zone at the rear of the embryo body. Initially, in
      the cephalic lobe there are no limbbuds; then the cheliceral buds emerge from the
      posterior part of the lobe. The stomodeum appears first in the anterior half of
      the cephalic lobe, but an oral groove forms and the mouth is displaced
      posteriorly within the groove. This repositioning allows space anteriorly for
      invagination (semilunar grooves) of epithelium for the brain and medial eyes. The
      mouth is directed ventrally in all stages of this study. The widespread
      chelicerae are initially posterior to the mouth, but later move anterior and
      dorsal to it. Small limbbud bulges on mesosomal segments disappear later and
      never become protruding appendages. Metasomal segments are produced free from the
      yolk surface in a ventral flexure beneath the embryo body. The telson starts as
      two spherical lobes, but later elongates and tapers distally, not yet developing
      the sharp sting (aculeus) seen in Silurian and all subsequent scorpions. The
      walking legs are digitigrade, as in most fossil aquatic scorpions. Segments are
      delineated in the appendages; the chelicerae and pedipalps are divided distally
      for chela (claw) formation. Bilateral swellings (limbbuds) on the third abdominal
      segment become larger than the others, indicating the site of pectine formation.
      The early fin-like pectines are somewhat posterior in the mesosoma, suggesting
      ancestral swimming, maneuvering, and balancing for the elongate abdomen. The
      pectinal surface is initially smooth but later transverse striations increase the
      surface area as a possible respiratory adaptation. Pectinal teeth (present in
      Silurian and all subsequent scorpions) and forward movement and merging of
      anterior abdominal segments are not yet evident in embryos of this study.

PMID- 11599018
TI  - Deformation and three-dimensional displacement of fibers in isometrically
      contracting rat plantaris muscles.
AB  - In this study, the deformation of different fibers of the rat m. plantaris during
      "isometric" contractions at different muscle lengths was considered. Because the
      m. plantaris has an obviously inhomogeneous architecture, its fibers on the
      medial side of the muscle belly are judged to be shorter than those on the
      lateral side of it. It was expected that longitudinal deformation of different
      fibers would vary accordingly. A 3D video analysis of contracting muscle showed
      that longitudinal strain of fibers as a function of muscle length does not differ
      between fibers on different sides of the muscle. Apart from longitudinal
      shortening, the fibers were also displaced laterally during a contraction. The
      fibers displaced during a contraction in a direction perpendicular to their
      longitudinal axis. The displacement of the fibers occurred asymmetrically,
      resulting in a helical deformation of the whole muscle. It is concluded that the
      asymmetric displacement and the helical deformation must result from transversal
      forces between the fibers. It is hypothesized that these transversal forces
      cancel out differences in longitudinal strains that might exist between fibers.

PMID- 11599019
TI  - QSAR: hydropathic analysis of inhibitors of the p53-mdm2 interaction.
AB  - To date, a number of p53-derived peptides have been evaluated in vitro for their
      ability to inhibit the carcinogenic p53-mdm2 interaction. Design of second
      generation nonpeptidic compounds requires the reduction of large peptide
      structures down to small molecules maintaining the proper spatial arrangement of
      key functional groups. Molecular modeling software exists that can predict and
      rank intermolecular interactions from the p53-mdm2 complex crystal structure.
      Such analyses can yield a pharmacophore model suitable as a search query for a 3D
      chemical database to generate new lead compounds. As preliminary validation of
      this methodology, the Hydropathic INTeractions (HINT) program has been used to
      generate noncovalent interaction measurements between reported peptide inhibitors
      and mdm2. Quantitative structure-activity relationships were developed expressing
      peptide activity as a linear combination of hydropathic descriptors. In general,
      HINT measurements accurately modeled the effects of even single-atom alterations
      of the p53-peptide structure on activity, accounting for 70-90% of variation in
      experimental inhibition constants. These results surpassed those of a recently
      described molecular dynamics-based approach and required significantly less
      computation time. In conclusion, the HINT program can be integrated into the drug
      design cycle for next-generation p53-mdm2 complex inhibitors with confidence in
      its ability to simulate this noteworthy protein-protein interaction.

PMID- 11599020
TI  - Molecular dynamics of HIV-1 reverse transcriptase indicates increased flexibility
      upon DNA binding.
AB  - HIV-1 reverse transcriptase (RT) is one of the main targets for drugs used in the
      treatment of AIDS, among them, the non-nucleoside RT inhibitors (NNRTIs). The
      flexibility of RT unliganded and complexed to double-stranded DNA (RT/dsDNA), in
      water, has been studied by means of molecular dynamics. The simulations show that
      RT flexibility depends on its ligation state. The RT/dsDNA trajectories show
      larger fluctuations in the atomic positions than uncomplexed RT, particularly at
      the tips of the p66 fingers and thumb subdomains. This increased flexibility is
      consistent with the ability of the p66 fingers of the RT/dsDNA complex to close
      down after the binding of a deoxynucleoside triphosphate (dNTP) molecule, as
      observed in the crystal structures of RT/dsDNA bound to dNTP. The two
      complexation states present different patterns of concerted motions, indicating
      that the bound dsDNA alters RT flexibility. The motions of amino acid residues
      that form the non-nucleoside RT inhibitor binding pocket upon complexation with a
      NNRTI are anticorrelated with the p66 fingers (in RT/dsDNA) and correlated to the
      RNase H subdomain (unliganded RT). These concerted motions indicate that binding
      of a NNRTI could alter the flexibility of the subdomains whose motions are
      correlated to those of the binding pocket.

PMID- 11599021
TI  - Successful molecular dynamics simulation of two zinc complexes bridged by a
      hydroxide in phosphotriesterase using the cationic dummy atom method.
AB  - I report herein two 2.0 ns (1.0 fs time step) MD simulations of two zinc
      complexes bridged by a hydroxide in phosphotriesterase (PTE) employing the
      nonbonded method and the cationic dummy atom method that uses virtual atoms to
      impose orientational requirement for zinc ligands. The cationic dummy atom method
      was able to simulate the four-ligand coordination of the two zinc complexes in
      PTE. The distance (3.39 +/- 0.07A) between two nearby zinc ions in the time
      average structure of PTE derived from the MD simulation using the cationic dummy
      atoms matched that in the X-ray structure (3.31 +/- 0.001A). Unequivocally, the
      time-average structure of PTE was able to fit into the experimentally determined
      difference electron density map of the corresponding X-ray structure. The results
      demonstrate the practicality of the cationic dummy atom method for MD simulations
      of zinc proteins bound with multiple zinc ions. In contrast, a 2.0 ns (1.0 fs
      time step) MD simulation using the nonbonded method revealed a striking
      difference in the active site between the X-ray structure and the time-average
      structure that was unable to fit into the density map of PTE. The results suggest
      that caution should be used in the MD simulations using the nonbonded method.

PMID- 11599022
TI  - New insights into the mechanism of protein-protein association.
AB  - Association of a protein complex follows a two-step mechanism, with the first
      step being the formation of an encounter complex that evolves into the final
      complex. Here, we analyze recent experimental data of the association of TEM1
      beta-lactamase with BLIP using theoretical calculations and simulation. We show
      that the calculated Debye-Huckel energy of interaction for a pair of proteins
      during association resembles an energy funnel, with the final complex at the
      minima. All attraction is lost at inter-protein distances of 20 A, or rotation
      angles of >60 degrees from the orientation of the final complex. For faster
      associating protein complexes, the energy funnel deepens and its volume
      increases. Mutations with the largest impact on association (hotspots for
      association) have the largest effect on the size and depth of the energy funnel.
      Analyzing existing evidence, we suggest that the transition state along the
      association pathway is the formation of the final complex from the encounter
      complex. Consequently, pairs of proteins forming an encounter complex will tend
      to dissociate more readily than to evolve into the final complex. Increasing
      directional diffusion by increasing favorable electrostatic attraction results in
      a faster forming and slower dissociating encounter complex. The possible
      applicability of electrostatic calculations for protein-protein docking is
      discussed.

PMID- 11599023
TI  - Analysis of antibodies of known structure suggests a lack of correspondence
      between the residues in contact with the antigen and those modified by somatic
      hypermutation.
AB  - Forty unique murine antibody-antigen complexes determined at 2.5 A or less
      resolution are analyzed to determine whether the residues in direct contact with
      the antigen are modified by somatic hypermutation. This was done by taking
      advantage of the recent characterization of the pool of Vkappa germline genes of
      the mouse. The average number of residues in contact with the antigen in the V(L)
      gene, which contains the CDRL-1, CDRL-2, and all but one residue of CDRL-3, was
      six. The average number of somatic mutations was similar (around five). However,
      as many as 53% of the antibodies did not show somatic replacements of residues in
      contact with the antigen. Another 28% had only one. Overall, the frequency of
      antibodies with increasing number of somatic replacements in residues in contact
      with the antigen decreased exponentially. A possible explanation of this finding
      is that mutations in the contacting residues have an adverse effect on the
      antigen-antibody interaction. This implies that most of the observed mutations
      are those remaining after negative (purifying) selection. Therefore, efficient
      strategies of site-directed mutagenesis to improve the affinity of antibodies
      should be focused on residues other than those directly interacting with the
      antigen.

PMID- 11599024
TI  - Bias-free separation of internal and overall motion of biomolecules.
AB  - Collective internal motions are known to be important for the function of
      biological macromolecules. It has been discussed in the past whether the
      application of superimposing algorithms to remove the overall motion from a
      structural ensemble introduces artificial correlations between distant atoms.
      Here we present a new method to eliminate residual rotation and translation from
      cartesian modes derived from a normal mode analysis or from a principal component
      analysis. Bias-free separation is based on the idea that the addition of modes of
      pure rotation/translation can compensate the residual overall motion. Removal of
      overall motion must reduce the "total amount of motion" (TAM) in the mode. Our
      algorithm allows to back-calculate revised covariance matrices. The approach was
      applied to two model systems that show residual overall motion, when analyzed
      using all atoms as reference for the superimposing algorithm. In both cases, our
      algorithm was capable of eliminating residual covariances caused by the overall
      motion, while retaining internal covariances even for very distant atoms. A
      structural ensemble obtained for a 13-ns molecular dynamics simulation of the
      protein Ribonuclease T1 showed a covariance matrix of the corrected modes with
      significantly sharper contours after applying the bias-free separation.

PMID- 11599025
TI  - Crystal packing interaction that blocks crystallization of a site-specific DNA
      binding protein-DNA complex.
AB  - We present here three high-resolution crystal structures of complexes between the
      DNA-binding domain of the heat-shock transcription factor (HSF) and DNA
      oligomers. Although the DNA oligomers contain HSF's specific binding sequence,
      called a heat-shock element, the crystal structures do not contain the specific
      protein-DNA complex. In one crystal structure, the 10 base pair DNA oligomer is
      statically disordered. In the other two related structures, the 12 base pair DNA
      oligomers are in unique positions, but the protein-DNA contacts in these two
      crystals are not sequence specific. In all three structures, the DNA appears to
      act as a rigid, polyanion scaffold to support columns of proteins in a
      crystalline lattice. A robust crystal packing interface between protein monomers
      obscures the true DNA-binding surface, known from previous genetic and
      biochemical studies. By redesigning the protein to interfere with the crystal
      lattice contacts, we were able to obtain physiologically relevant crystals in a
      specific protein-DNA complex. Thus, a crystal-packing interface was able to
      prevent the weak, but physiological relevant interactions between a protein and
      DNA.

PMID- 11599026
TI  - Lactoferrin-melanin interaction and its possible implications in melanin
      polymerization: crystal structure of the complex formed between mare lactoferrin
      and melanin monomers at 2.7-A resolution.
AB  - The concentration of melanin determines the intensity of colors of the skin and
      hair of animals. Melanin pigments are tyrosine-based polymers formed in
      melanocytes within specialized organelles called melanosomes. In order to
      understand the mechanism of melanin polymerization, lactoferrin, a basic protein
      with a pI value of 9.0, has been used to produce melanin. Lactoferrin is a
      monomeric iron-binding protein with a molecular weight of 80 kDa. The crystals of
      lactoferrin were soaked in a solution containing dihydroxyphenylalanine (DOPA)
      and tyrosinase enzyme. These crystals were used for X-ray intensity data
      collection. The intensity data were collected to 2.7-A resolution to an overall
      completeness of 91% with an R(sym) of 0.071. The crystals belong to orthorhombic
      space group P2(1)2(1)2(1) with cell dimensions: a = 85.0 A, b = 99.8 A, c = 103.4
      A. The structure was determined by molecular replacement method, using the model
      of diferric mare lactoferrin, and refined to an R-factor 0.215 (R(free) = 0.287)
      for all the data to 2.7-A resolution. The final model comprises 5,281 protein
      atoms from 689 amino acids, 2Fe(3+), 2CO(2-)(3) ions, 2 indole-5,6-quinone
      molecules (IQ), and 73 water molecules. Two IQ molecules, one in each lobe, bind
      to lactoferrin. In the C-lobe, the IQ binds in the iron-binding cleft, whereas in
      the N-lobe, it is located in the side pocket between two alpha-helices, filled
      with solvent molecules in the native iron-saturated mare lactoferrin. The IQ
      molecules interact with protein molecule mainly through glutamic acid in both
      lobes, without significant perturbation to the protein structure. The orientation
      of N- and C-lobes in the present structure is similar to that observed in the
      native iron-saturated protein. However, as a result of the binding of IQ
      molecules, the orientations of the domains N1, N2 and C1, C2 in the two cases
      differ slightly.

PMID- 11599027
TI  - Theoretical study of the conformation of the lipoamide arm in a mutant H protein.
AB  - The lipoamide arm of the H protein plays a pivotal role in the catalytic cycle of
      the glycine decarboxylase complex (GDC) by being successively methylamine loaded
      (Hmet), reduced (Hred), and oxidized (Hox). In a previous study, we calculated
      free-energy surfaces as a function of the lipoamide arm position of the three
      forms of the wild-type protein and found close agreement with the available
      experimental data. Our simulations, together with crystallographic and NMR data,
      showed that the methylamine-loaded arm is locked in a cavity by interaction with
      Ser12, Glu14, and Asp67. In this work, we investigate the behavior of the
      methylamine-loaded form of a mutant H protein (HEA) where Glu14 has been replaced
      by Ala. We find that the arm can still be held in the cavity but that the energy
      barrier to release of the arm is halved from approximately 40 kcal mol(-1) for
      Hmet to approximately 12 kcal mol(-1) for HEA. To compensate for the loss of
      Glu14, the methylamine group shifts toward Ser66 in the mutant form. These
      results provide a structural basis for the equilibrium between the loaded and the
      unloaded forms of the arm observed by Gueguen et al. (Gueguen et al., J Biol Chem
      1999;274:26344-26352) in HEA.

PMID- 11599028
TI  - Linear programming optimization and a double statistical filter for protein
      threading protocols.
AB  - The design of scoring functions (or potentials) for threading, differentiating
      native-like from non-native structures with a limited computational cost, is an
      active field of research. We revisit two widely used families of threading
      potentials: the pairwise and profile models. To design optimal scoring functions
      we use linear programming (LP). The LP protocol makes it possible to measure the
      difficulty of a particular training set in conjunction with a specific form of
      the scoring function. Gapless threading demonstrates that pair potentials have
      larger prediction capacity compared with profile energies. However, alignments
      with gaps are easier to compute with profile potentials. We therefore search and
      propose a new profile model with comparable prediction capacity to contact
      potentials. A protocol to determine optimal energy parameters for gaps, using LP,
      is also presented. A statistical test, based on a combination of local and global
      Z-scores, is employed to filter out false-positives. Extensive tests of the new
      protocol are presented. The new model provides an efficient alternative for
      threading with pair energies, maintaining comparable accuracy. The code,
      databases, and a prediction server are available at
      http://www.tc.cornell.edu/CBIO/loopp.

PMID- 11599029
TI  - Integrated graphical analysis of protein sequence features predicted from
      sequence composition.
AB  - Several protein sequence analysis algorithms are based on properties of amino
      acid composition and repetitiveness. These include methods for prediction of
      secondary structure elements, coiled-coils, transmembrane segments or signal
      peptides, and for assignment of low-complexity, nonglobular, or intrinsically
      unstructured regions. The quality of such analyses can be greatly enhanced by
      graphical software tools that present predicted sequence features together in
      context and allow judgment to be focused simultaneously on several different
      types of supporting information. For these purposes, we describe the SFINX
      package, which allows many different sets of segmental or continuous-curve
      sequence feature data, generated by individual external programs, to be viewed in
      combination alongside a sequence dot-plot or a multiple alignment of database
      matches. The implementation is currently based on extensions to the graphical
      viewers Dotter and Blixem and scripts that convert data from external programs to
      a simple generic data definition format called SFS. We describe applications in
      which dot-plots and flanking database matches provide valuable contextual
      information for analyses based on compositional and repetitive sequence features.
      The system is also useful for comparing results from algorithms run with a range
      of parameters to determine appropriate values for defaults or cutoffs for large
      scale genomic analyses.

PMID- 11599030
TI  - Role of amino acid residues in left-handed helical conformation for the
      conformational stability of a protein.
AB  - Our previous study of six non-Gly to Gly/Ala mutant human lysozymes in a left
      handed helical region showed that only one non-Gly residue at a rigid site had
      unfavorable strain energy as compared with Gly at the same position (Takano et
      al., Proteins 2001; 44:233-243). To further examine the role of left-handed
      residues in the conformational stability of a protein, we constructed ten Gly to
      Ala mutant human lysozymes. Most Gly residues in human lysozyme are located in
      the left-handed helix region. The thermodynamic parameters for denaturation and
      crystal structures were determined by differential scanning calorimetry and X-ray
      analysis, respectively. The difference in denaturation Gibbs energy (DeltaDeltaG)
      for the ten Gly to Ala mutants ranged from + 1.9 to -7.5 kJ/mol, indicating that
      the effect of the mutation depends on the environment of the residue. We confirm
      that Gly in a left-handed region is more favorable at rigid sites than non-Gly,
      but there is little difference in energetic cost between Gly and non-Gly at
      flexible sites. The present results indicate that dihedral angles in the backbone
      conformation and also the flexibility at the position should be considered for
      analyses of protein stability, and protein structural determination, prediction,
      and design.

PMID- 11599031
TI  - Structure of an anti-HIV monoclonal Fab antibody fragment specific to a gp120 C-4
      region peptide.

PMID- 11599032
TI  - In vivo single-voxel proton MR spectroscopy in brain lesions with ring-like
      enhancement.
AB  - It is often difficult to make a correct diagnosis of ring-like enhanced lesions
      on Gd-enhanced MR brain images. To differentiate these lesions using proton MR
      spectroscopy (1H-MRS), we retrospectively evaluated the correlation between the
      1H-MR spectra and histopathological findings. We evaluated proton MR spectra
      obtained from the lesions in 45 patients, including metastasis (n = 19),
      glioblastoma (n = 10), radiation necrosis (n = 7), brain abscess (n = 5), and
      cerebral infarction (n = 4). The rate of misdiagnosis was found to be lowest at
      the threshold level of 2.48 for the (choline containing compounds)/(creatine and
      phosphocreatine) ratio (Cho/Cr) obtained from the whole lesions, which include
      the enhanced rim and the non-enhanced inner region. That is, the positively
      predictive values of a Cho/Cr greater than 2.48 for diagnosing metastasis or
      glioblastoma was 88.9 and 60.0%, respectively, and the positively predictive
      value of a Cho/Cr less than 2.48 for diagnosing radiation necrosis or cerebral
      infarction was 71.4 and 100%, respectively. For further differentiating between
      metastasis and glioblastoma, information about the presence and absence of an N
      acetyl-aspartate (NAA) peak and lipid- or lactate-dominant peak was found to be
      useful. In 73.7% of metastasis cases a lipid-dominant peak was observed in the
      whole lesion without an NAA peak in the inner region, whereas the same pattern
      was observed in only 10% of the glioblastoma cases. Correlation with the
      histopathological findings showed that a high Cho signal is suggestive of
      neoplasm. Lipid signal in the non-enhanced central region was correlated to
      necrosis. Lactate signals were often observed in glioblastoma, abscess and
      sometimes metastasis, presumably reflecting the anaerobic glycolysis by the
      living cells in the ring-like enhanced rim. Single-voxel proton MR spectroscopy
      may serve as a potential tool to provide useful information of differentiation of
      ring-like enhanced lesions that cannot be diagnosed correctly using enhanced MR
      images alone.

PMID- 11599033
TI  - T1 relaxation times for viability evaluation of the engrafted and the native
      liver in a rat model of heterotopic auxiliary liver transplantation: a pilot
      study.
AB  - Following a heterotopic auxiliary liver transplantation, commonly used
      measurements are either invasive or non-indicative of individual viability of the
      coexisting engrafted and native livers. Magnetic resonance imaging (MRI) was
      therefore tested for its potential to monitor the post-transplant hepatic
      viability in a rat model. Thirteen Wistar rats were systematically evaluated with
      MRI and serum biochemical liver parameters. Post-transplant complications and the
      causes of animal death were identified by autopsy and histo-pathological
      examinations. The data of the healthy survivors were compared with those of the
      rats that developed complications. On MRI, the hepatic complications could be
      depicted in the individual livers. A specific pattern of signal evolution was
      found in the livers of the healthy survivors: the mean T1 relaxation times of the
      engrafted livers increased immediately after transplantation (476 +/- 64 ms, mean
      +/- standard deviation, pre-operative; 730 +/- 48 ms, week 1) and then declined
      steadily to a 3 month value of 489 +/- 246 ms, while, following a transient first
      rise (476 +/- 64 ms, pre-operative; 589 +/- 28 ms, week 1), the mean T1 value of
      the native livers increased again 4 weeks after surgery and reached a 3 month
      value of 859 +/- 43 ms. However, in the rats with various complications, the mean
      T1 relaxation times of the engrafted livers continued to increase throughout the
      first post-operative month (760 +/- 48 ms, week 1; 922 +/- 76 ms, week 4), while
      that of the native liver only varied mildly (546 +/- 25 ms, week 1; 473 +/- 25
      ms, week 4). After the first post-transplant week, the healthy engrafted livers
      could already be distinguished from those with complications by a significant
      decrease in T1 relaxation times. These data suggest that, besides demonstrating
      major complications, MRI may allow one to monitor the viability of each liver by
      analysing the relative signal intensity and T1 relaxation times after a
      heterotopic auxiliary liver transplantation.

PMID- 11599034
TI  - Therapeutic efficacy of 5-fluorouracil-loaded microspheres on rat glioma: a
      magnetic resonance imaging study.
AB  - The aim of this work was to assess the therapeutic efficacy of an intratumoral
      bolus injection of 5-fluorouracil (FU) compared to that of drug loaded in
      biodegradable microspheres, for the treatment of brain tumour. Experiments were
      carried out using a fast-growing C6-glioma rat model. The therapeutic protocols
      were performed 12 days after the injection of glioma cells. At this stage, the
      tumours were installed and the mean volume was 13 +/- 2 microl as measured by
      proton magnetic resonance (MR) imaging. This technique was used for the follow-up
      of the tumour volume with respect to time and therapy. In terms of rat survival,
      both therapies induced a significant 50% increase in animal life span (p < 0.05)
      compared to animals receiving no drug or unloaded microspheres. Whilst no cure
      was observed, analysis of the MR images showed that the local and sustained
      delivery of FU slowed the tumour development in the vicinity of the microspheres
      by a factor of 3, compared with the bolus intratumoral injection.

PMID- 11599036
TI  - Current awareness in NMR in biomedicine.

PMID- 11599035
TI  - Basic studies on the equivalent cross-relaxation rate imaging (equivalent CRI)-
      phantom studies.
AB  - We have studied saturation transfer in hydrophilic, cross-linked copolymer gels
      from irradiated polymer protons to observed water protons, using f2 (ppm)
      profiles of [1 - (I(infinity)/I(0))], [(I(0)/I(infinity)) - 1] or 1/T(IS)(H2O),
      where I(0) and I(infinity) are the longitudinal magnetization of the observed
      water protons before and after long-time-f2-irradiation on polymer protons,
      respectively, and 1/T(IS)(H2O) is the cross-relaxation rate. (A) [1 -
      (I(infinity)/I(0))] (magnetization transfer ratio, MTR) was used in magnetic
      resonance imaging (MRI) as the MTR imaging. 1/T(IS)(H2O) (cross-relaxation rate)
      was used in the imaging of the magnetization transfer rate constant. This method
      was quite time-consuming compared with MTR imaging. However, f2 (ppm) profiles of
      [(I(0)/I(infinity)) - 1] correlated well with corresponding profiles of
      1/T(IS)(H2O), because [(I(0)/I(infinity)) - 1] is equal to
      1/[T(IS)(H2O)/T1(H2O)]. These results lead us to the conclusion that
      [(I(0)/I(infinity)) - 1] might be applicable to cross-relaxation rate (CR)-like
      imaging, i.e. equivalent CRI. (B) W (%) (dry weight) profiles of
      [(I(0)/I(infinity)) - 1] and 1/T(IS)(H2O), obtained by near-resonance f2
      irradiation, seem to indicate participation of molecular rigidity and an amount
      of bound water. However, those values, monitored with off-resonance f2
      irradiation, seem to be independent of monomer composition and to indicate mainly
      participation of rigidity, i.e. W (%) of copolymer gels.

PMID- 11599037
TI  - Primordial germ cell-somatic cell partnership: a balancing cell signaling act.
AB  - Recent studies demonstrate that the normal progression of the germ cell lineage
      during gonadogenesis involves a delicate balance of primordial germ cell survival
      and death factors generated by surrounding somatic cells. This balance operates
      in a different fashion in females and males. The fine tuning primordial germ cell
      specification in the wall of the yolk sac, migration through the hindgut and
      dorsal mesentery, and colonization in the urogenital ridges involves the temporal
      and spatial activation of the following signaling pathways: Primordial germ cell
      specification involves bone morphogenetic proteins 2, 4 and 8b, and their
      migration is facilitated by the c-kit receptor-ligand duet. When colonization
      occurs: (1) neuregulin-beta ligand is expressed and binds to an ErbB2-ErbB3
      receptor tyrosine kinase heterodimer on primordial germ cells; (2) Vasa, an
      ortholog of the Drosophila gene vasa, member of an ATP-dependent RNA helicase of
      the DEAD (Asp-Glu-Ala-Asp)-box family protein is also expressed by primordial
      germ cells; (3) Bcl-x (cell survival factor) and Bax (cell death factor) join
      forces to modulate the first burst of primordial germ cell apoptosis; (4)
      Cadherins, integrins, and disintegrins bring together primordial germ cells and
      somatic cells to organize testis and ovary. Information on other inducers of
      primordial cell survival, such as TER (teratoma) factor, is beginning to emerge.

PMID- 11599038
TI  - Comparison of gene transcription in cloned bovine embryos produced by different
      nuclear transfer techniques.
AB  - The efficiency of animal production using cloning technology is still relatively
      low and research to determine a more efficient nuclear transfer procedure is
      ongoing. One approach which may be informative in assessing the viability of
      nuclear transfer embryos is the analysis of embryonic gene expression. Using RT
      PCR techniques we have previously detected the aberrant expression of FGF4, FGFr2
      and IL6 in a significant proportion of bovine granulosa cell-derived nuclear
      transfer embryos, which correlated with a limited developmental potential in
      vivo. In order to analyse the effect of different donor cell nuclei on embryonic
      gene expression we have now analysed the expression of these genes in nuclear
      transfer embryos reconstructed with fetal epithelial cell nuclei. In addition, we
      have compared the expression of these genes in bovine nuclear transfer embryos
      produced by cell fusion or direct injection with variations in the timing of
      oocyte activation. In all nuclear transfer embryos analysed, FGFr2 and IL6
      transcripts were detected at a similar rate to that in IVF embryos. However, the
      absence of FGF4 transcripts was again evident in a large proportion of nuclear
      transfer embryos and most significantly in those embryos whose development was
      activated almost immediately following the transfer of the donor nucleus. The
      results demonstrate the effects that different donor cell lines and different
      nuclear transfer procedures may have on the expression of developmentally
      important genes in nuclear transfer embryos.

PMID- 11599039
TI  - Expression of retinol-binding protein messenger RNA and retinoic acid receptors
      in preattachment bovine embryos.
AB  - In cattle, retinoic acid (RA) has been indirectly associated with developmental
      potential of the embryo. RA is transported by retinol-binding protein (RBP) and
      actions of RA are mediated by several subtypes of nuclear retinoic acid receptors
      (RAR). Bovine embryos, produced in vitro from oocytes harvested from ovaries
      collected at a local abattoir, were frozen in liquid nitrogen at the oocyte, 2-,
      4-, 8-, 16 to 20-cell, morula, blastocyst, and hatched blastocyst stages.
      Employing reverse transcription polymerase chain reaction (RT-PCR) we
      investigated mRNA expression for RBP, RARalpha, RARbeta, RARgamma, and
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Total RNA was extracted from 25
      pooled embryos at each stage and RT-PCR analysis was repeated thrice. GAPDH
      transcript was detected in all stages. Transcripts for RBP, RARalpha, and
      RARgamma were also detected in all stages from the oocyte through to the hatched
      blastocyst. Expression of RARbeta was not detected at any stage. Whole-mount
      immunohistochemistry was performed with intact and hatched blastocysts using
      polyclonal antibodies against RARalpha and RARgamma2 to investigate if these
      embryonic mRNAs were translated to the mature protein. Strong immunostaining was
      observed for both RARalpha and RARgamma2 in the inner cell mass and trophectoderm
      of intact and hatched blastocysts. Expression of mRNA for RBP, RARalpha,
      RARgamma, and of the RARalpha and RARgamma2 receptor proteins in the bovine
      embryo suggests that RA is likely to directly regulate gene expression during
      preimplantation development in that species.

PMID- 11599040
TI  - Expression of homeobox-containing genes in cDNA libraries derived from cattle
      oocytes and preimplantation stage embryo.
AB  - The homeobox-containing gene family plays a pivotal role in regulating,
      patterning, and axial morphogenesis in the developing embryo. But there is still
      very little known about the expression and function of these genes in mammalian
      oocytes and preimplantation stage embryos. In this study we have used degenerate
      primers corresponding to the highly conserved regions of Antennapedia class
      homeodomains as a rapid and an efficient method to survey bovine cDNA libraries
      derived from unfertilised oocytes, single 2-cell, 4-cell, 8-cell, morula, and
      blastocyst stage embryos for the presence of homeobox sequences. Our results
      provide, for the first time, evidence for the transcription of Hoxa3 and Hoxd1 in
      oocytes; Cdx1 and Cdx2 in the 2-cell; Cdx1, Hoxa1, Hoxd1, and Hoxd4 in the 4
      cell; Cdx1, Hoxa1, and Hoxc9 in the 8-cell; Cdx2, Hoxb9, and Hoxc9 in the morula;
      Cdx2, Hoxb7, Hoxb9, and Hoxc9 in blastocyst stage cattle embryos. These are
      candidate genes for the developmental capacity of in vivo and in vitro produced
      bovine embryos.

PMID- 11599041
TI  - Acute cyclophosphamide exposure has germ cell specific effects on the expression
      of stress response genes during rat spermatogenesis.
AB  - Exposure of male rats to cyclophosphamide, a commonly used anticancer and
      immunosuppressive drug, has been shown to alter fertility and progeny outcome in
      a male germ cell phase-specific manner. The effect of toxicant exposure on male
      germ cells depends in part on the stress response mechanisms present during the
      different stages of spermatogenesis. To assess how acute cyclophosphamide
      exposure affects the expression of stress response genes, we examined the
      expression of 216 genes, using gene expression arrays, in isolated rat
      spermatogenic cell types (pachytene spermatocytes, round spermatids, and
      elongating spermatids). Cyclophosphamide exposure affected gene expression in all
      cell types but most dramatically in round spermatids. Increased transcript levels
      were observed for 30 genes in round spermatids compared to seven genes in
      pachytene spermatocytes and two in elongating spermatids. The expression of genes
      involved in apoptosis, DNA-damage recognition and repair, transcriptional
      activation, and in the heat shock protein-chaperone response was most affected by
      cyclophosphamide in round spermatids. Our results demonstrate that
      cyclophosphamide alters the expression of stress response genes during
      spermatogenesis in a germ cell-specific manner. The greater response of round
      spermatids to cyclophosphamide suggests that this cell type may be more
      susceptible to the damaging effects induced by this drug, possibly due to the
      chromatin remodeling that is taking place at this stage of spermatogenesis. This
      observation is consistent with the reported higher level of abnormal progeny
      outcome seen when the germ cells were first exposed to cyclophosphamide as round
      spermatids.

PMID- 11599042
TI  - Cysteine protease inhibitor is specifically expressed in pre- and early
      vitellogenic oocytes from the brook trout periovulatory ovary.
AB  - A cDNA fragment hybridizing with a transcript abundant in the periovulatory ovary
      was obtained while performing subtractive cloning on brook trout ovulatory and
      postovulatory ovarian tissue. Using this fragment as a probe, a 478 bp full
      length cDNA was obtained by screening an ovulatory ovarian cDNA library. This
      cDNA presumably codes for an 88 amino acid protein that is structurally related
      to a new family of cysteine protease inhibitors characterized by the presence of
      a type I thyroglobulin motif in the amino acid sequence. Therefore, the protein
      was tentatively named an oocyte cysteine protease inhibitor (OCPI). On Northern
      blots, the OCPI cDNA hybridizes with a 0.5 kb transcript present in the ovary
      during the periovulatory period. The OCPI transcript and protein were localized
      to the cytoplasm of pre- and early-vitellogenic oocytes. On Northern blots of RNA
      from other tissues, the OCPI transcript was detected only in the ovary. On
      Western blots, OCPI was detected in the ovarian tissue at all periovulatory
      stages tested. The specific localization of both OCPI transcript and protein to
      pre- and early-vitellogenic oocytes and the structural similarity to protease
      inhibitors, suggest that OCPI might be involved in the protection of oocytes
      during the periovulatory period or in the regulation of yolk formation and
      degradation.

PMID- 11599043
TI  - Mouse oocytes and preimplantation embryos bear the two sub-units of interferon
      gamma receptor.
AB  - Cytokines and growth factors play important roles in implantation and maintenance
      of pregnancy, but also during early development. Among them interferon-gamma
      (IFNgamma) is highly expressed by mammalian trophoblast cells during implantation
      and seems to be involved in some cases of pregnancy loss. In the present study we
      investigated the possible presence of IFNgamma receptors (IFNGR) on mouse oocytes
      and preimplantation embryos. The two receptor chains IFNgammaRalpha (IFNGR-1) and
      IFNgammaRbeta (IFNGR-2) have been detected by indirect immunofluorescence at the
      surface of mouse oocytes (in germinal vesicle and metaphase II stages), as well
      as at all stages of in vitro embryo development from the one-cell to blastocyst
      stage. IFNGR appeared to colocalize partly with ganglioside GM1 at the cell
      surface of oocytes and embryos, indicating a possible preferential localization
      of this receptor in "rafts" microdomains. This was analyzed in more detail using
      software developed in the laboratory. IFNgamma was found to bind to its receptor
      at all stages analyzed. RT-PCR and Southern blot experiments confirmed the
      presence of the transcriptionally regulated IFNGR-2 chain mRNA, in mouse oocytes
      and preimplantation embryos. These results show, for the first time, that mouse
      oocytes and preimplantation embryos bear a complete and theoretically functional
      IFNGR, suggesting that this cytokine could play a role during early development.

PMID- 11599044
TI  - Distinct roles for Distal-less genes Dlx3 and Dlx5 in regulating ectodermal
      development in Xenopus.
AB  - In vertebrates, there are six or more copies of genes related to the Drosophila
      pattern formation homeodomain gene Distal-less. Among this family, Dlx3 and Dlx5
      share extensive sequence homology and have similar, but distinctive, expression
      patterns, suggesting that these two factors may have substantially redundant
      developmental functions. Here we show that at the earliest phases of
      embryogenesis in Xenopus, there are significant differences between Dlx3 and Dlx5
      expression and that this correlates with different functions in the restriction
      of neural crest and neural plate boundaries, respectively.

PMID- 11599045
TI  - Type II iodothyronine deiodinase is preferentially expressed in rainbow trout
      (Oncorhynchus mykiss) liver and gonads.
AB  - It is well admitted that thyroid hormones (TH) play a role in the development of
      vertebrates. The major secretory product of the thyroid is a pro-hormone, T(4),
      which is activated in peripheral tissues by outer ring deiodination to T(3). We
      have isolated from rainbow trout testis, a full length cDNA encoding type II
      iodothyronine deiodinase (rtD2). The cDNA was 2410 nucleotides long and coded for
      a polypeptide of 264 amino acids including a selenocysteine residue. The
      predicted molecular weight of rtD2 was 29.3 kDa and the isoelectric point 8.71.
      The deduced amino acids sequence showed 80% identity with Fundulus heteroclitus
      D2 (fhD2) but only 68-69% identity with rat, mouse, and human D2. The 3' UTR
      contained a putative selenocysteine insertion sequence (SECIS) similar to that
      described in human cDNA. The rtD2 gene was isolated and the gene structure was
      similar to that described in human with two exons separated by a large intron. We
      studied rtD2 gene expression by Northern blot analysis using total RNA extracted
      from testis, ovary, and other tissues. We found a high expression of a 3 kb
      transcript in liver and in gonads. A lower expression was also detected in
      posterior kidney. In testis, rtD2 mRNA expression was dependent on spermatogenic
      stages: it increased at the onset of spermatogenesis. Our results show that the
      structural characteristics of the D2 protein and gene have been highly conserved
      during evolution. The rtD2 mRNA expression in the gonads suggests that rtD2 may
      be a key factor regulating local supply of active T(3) during rainbow trout
      gametogenesis.

PMID- 11599046
TI  - Expression of myostatin pro domain results in muscular transgenic mice.
AB  - Myostatin, a member of the TGF-beta family, negatively regulates skeletal muscle
      development. Depression of myostatin activity leads to increased muscle growth
      and carcass lean yield. In an attempt to down-regulate myostatin, transgenic mice
      were produced with a ribozyme-based construct or a myostatin pro domain
      construct. Though the expression of the ribozyme was detected, muscle development
      was not altered by the ribozyme transgene. However, a dramatic muscling phenotype
      was observed in transgenic mice carrying the myostatin pro domain gene.
      Expression of the pro domain transgene at 5% of beta-actin mRNA levels resulted
      in a 17-30% increase in body weight (P < 0.001). The carcass weight of the
      transgenic mice showed a 22-44% increase compared with nontransgenic littermates
      at 9 weeks of age (16.05 +/- 0.67 vs. 11.16 +/- 0.28 g in males; 9.99 +/- 0.38
      vs. 8.19 +/- 0.19 g in females, P < 0.001). Extreme muscling was present
      throughout the whole carcass of transgenic mice as hind and fore limbs and trunk
      weights, all increased significantly (P < 0.001). Epididymal fat pad weight, an
      indicator of body fat, was significantly decreased in pro domain transgenic mice
      (P < 0.001). Analysis of muscle morphology indicated that cross-sectional areas
      of fast-glycolytic fibers (gastrocnemius) and fast-oxidative glycolytic fibers
      (tibialis) were larger in pro domain transgenic mice than in their controls (P <
      0.01), whereas fiber number (gastrocnemius) was not different (P > 0.05). Thus,
      the muscular phenotype is attributable to myofiber hypertrophy rather than
      hyperplasia. The results of this study suggest that the over-expression of
      myostatin pro domain may provide an alternative to myostatin knockouts as a means
      of increasing muscle mass in other mammals.

PMID- 11599047
TI  - Nuclear transfer in cattle with non-transfected and transfected fetal or cloned
      transgenic fetal and postnatal fibroblasts.
AB  - The efficiency of nuclear transfer (NT) using two primary cultures of fetal
      fibroblasts (FF1 and FF2) was compared vs. the same cultures transfected with an
      expression vector in which the bovine prochymosin coding sequence is placed under
      the control of the bovine alpha(S1)-casein promoter (TFF1 and TFF2). In addition,
      fibroblasts of a cloned transgenic fetus (TRFF1) derived from TFF1 and ear skin
      fibroblasts of a 1-month-old cloned transgenic calf (TRCF1) derived from TRFF1
      were used as nuclear donors. Embryos reconstructed from FF1 (44%) and FF2 (52%)
      developed to the blastocyst stage at a significantly (P < 0.05) higher rate than
      those derived from TFF1 (24%) and TFF2 (27%). The proportions of cleaved embryos
      and blastocysts were significantly (P < 0.05) higher with TRFF1 than with TRCF1
      used as nuclear donors (75 vs. 66% and 33 vs. 16%, respectively). Transfer of NT
      embryos derived from FF2 and TFF2 to recipients resulted in similar pregnancy
      rates on day 30 (52 and 48%, respectively). However, with TFF2 embryos, the
      majority of pregnancies (8/11; 73%) was lost in the first and second trimesters
      of gestation, whereas 4/11 (36%) pregnancies with FF2 embryos were lost during
      the full period of in vivo development. Of 11 FF2 and 6 TFF2 born calves (25 and
      13% of transferred embryos, respectively), 6 and 3 survived including one
      oversized FF2 calf. After transfer of TRFF1 and TRCF1 NT embryos to recipients,
      initial pregnancy rate was as a tendency higher in the TRFF1 (49%) than in the
      TRCF1 group (30%). The majority (14/17) of TRFF1 pregnancies and all TRCF1
      pregnancies were lost in the first and second trimester. A high proportion of
      TRFF1 calves (5/8) showed increased body weights, and only two calves which were
      also large survived. These findings demonstrate that (i) extended culture
      associated with transfection and selection procedures may induce changes of donor
      cells which markedly decrease the efficiency of nuclear transfer and (ii) these
      changes are not reversed by recloning.

PMID- 11599048
TI  - Glucose transporter expression is developmentally regulated in in vitro derived
      bovine preimplantation embryos.
AB  - Glucose is readily been taken up and utilized by preimplantation embryos from
      different species. However, a comprehensive analysis of the glucose transporter
      expression throughout preimplantation development is still missing. Here, we have
      investigated the expression of facilitative glucose transporters (Glut1-5 and 8)
      and sodium-dependent-glucose transporter (SGLT-I) in bovine oocytes and
      preimplantation embryos up to d16 of development, using RT-PCR and
      immunohistochemistry. The embryos were produced in vitro by IVM-IVF. Glut1,
      Glut3, Glut8, and SGLT-I were expressed in all stages studied. Glut4 transcripts
      were first detected at the blastocyst stage. Glut2 expression was restricted to
      the period of blastocyst elongation at d14 and d16. Transcription of the fructose
      transporter Glut5 started at the 8-/16-cell stage. Our results show a distinct
      expression pattern for glucose transporters during bovine embryo development in
      vitro indicating specialized functions for these isoforms at different
      developmental stages in bovine embryos. Mol. Reprod. Dev. 60:370-376,

PMID- 11599049
TI  - Effect of two activation treatments and age of blastomere karyoplasts on in vitro
      development of bovine nuclear transfer embryos.
AB  - The yield and quality of (a) parthenogenetic blastocysts produced by two
      activation treatments (cycloheximide [CHX] or 6-dimethylaminopurine [DMAP]) and
      (b) nuclear transfer blastocysts generated using these two activation treatments
      and three different ages of karyoplast derived from day 3, 4, or 5 in vitro
      produced donor embryos, were examined in order to define an optimal nuclear
      transfer protocol. The two activation protocols comprised calcium ionophore
      followed by either CHX or DMAP. Parthenogenetic blastocyst yields were greater (P
      < 0.001) following activation with DMAP than CHX (59.7 +/- 5.1 vs. 31.4 +/- 4.5
      [mean +/- SEM]). In contrast, nuclear transfer blastocyst rates per fused embryo
      were lower (P < 0.0001) using cytoplasts activated with DMAP. The individual
      rates using day 3, 4, and 5 donors and using CHX and DMAP activation treatments
      were 31.9 +/- 5.0, 31.7 +/- 6.2, 20.4 +/- 7.3 and 27.8 +/- 4.7, 20.1 +/- 7.5,
      12.7 +/- 8.3, respectively. Blastocyst rate per fused embryo was negatively
      correlated (P = 0.0091) with the total number of blastomeres per donor embryo.
      Despite this inverse relationship, the calculated potential blastocyst yield per
      donor embryo was positively correlated (P < 0.0048) to karyoplast age. The
      individual potential yields on days 3, 4, and 5 and for the two activation
      protocols (CHX and DMAP) were 4.7 +/- 0.8, 7.2 +/- 1.2, 10.1 +/- 2.1 and 3.8 +/-
      0.8, 5.5 +/- 2.1, 7.3 +/- 4.1, respectively. One possible explanation for the
      observed inverse relationship is that differentiation events during early
      cleavage are able to reduce the ability of the cytoplast to reprogram the
      transferred karyoplast and hence reduce blastocyst yields. The mechanism that
      mediates the differential effect of the CHX and DMAP on blastocysts yields
      between parthenogenetic and nuclear transfer embryos remains to be elucidated. In
      conclusion, the results indicate that although activation of oocytes with DMAP
      can produce a higher percentage of blastocysts, CHX activation is superior for
      use in nuclear transfer.

PMID- 11599050
TI  - Novel growth factor supporting survival of murine primordial germ cells: evidence
      from conditioned medium of ter fetal gonadal somatic cells.
AB  - The ter (teratoma, chromosome 18) mutation causes a deficiency of primordial germ
      cells (PGCs) in ter/ter embryos from the ter congenic mouse strain at 8.0 days
      post coitum (dpc). In order to analyse the function of the ter gene, here we
      examined effects of conditioned medium (CM) from 14.5 dpc testicular and ovarian
      somatic cells of +/+, +/ter, or ter/ter genotype on mouse PGCs "mixed-cultured"
      with own somatic cells on feeder cells. The results showed that +/+ and +/ter CM
      supported survival in 9.5 and 11.5 dpc ICR PGCs but ter/ter CM did not rescue
      TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)
      positive apoptosis in the PGCs though it did not affect 5-bromo-2-deoxyuridine
      incorporation in PGCs. This supportive substance in +/+ CM, not ter/ter CM, was
      characterized as soluble, heat labile, and larger than 30 kDa. We also found that
      several known growth factors for PGCs and their receptors were expressed in
      ter/ter testes as well as +/+ testes, suggesting the ter function is independent.
      Thus, it was concluded that fetal gonadal somatic cells express a novel PGC
      growth factor (designated as TER Factor) supporting survival of PGCs not somatic
      cells and that the PGC deficiency in ter/ter testes is caused by a loss of this
      factor.

PMID- 11599051
TI  - Effect of sperm cryopreservation on sperm DNA stability and progeny development
      in rainbow trout.
AB  - This study was carried out to test how sperm cryopreservation affected nuclear
      DNA stability and whether progeny development was modified when eggs were
      fertilized with cryopreserved spermatozoa. The "comet assay" (alkaline single
      cell gel electrophoresis assay) was adapted to trout spermatozoa to estimate DNA
      stability as measured by alkali-induced DNA strand break formation. Because trout
      eggs develop in water after fertilization (oviparous species) and that eggshell
      is easy to clear up after fixative treatment, progeny development was assessed
      from the blastodisc flattening stage of the embryos to the first feeding stage of
      the hatched fries by direct observation. All parameters under study were analyzed
      on each sperm and comparisons between parameters were made using paired data.
      Freeze-thawing of sperm slightly but significantly increased the percentage of
      nuclei showing altered DNA after comet assay. This increase was correlated to the
      decrease in fertilization rates of sperm, but the absolute percentage of altered
      nuclei was not predictive of the absolute fertilization ability of sperm.
      Assessment of progeny development showed that survival rate and abnormality rate
      obtained after fertilization with cryopreserved sperm were not different from
      those obtained with fresh sperm. It is concluded that trout sperm
      cryopreservation only slightly affected sperm DNA stability and that the use of
      cryopreserved spermatozoa did not impair offspring survival and quality.

PMID- 11599052
TI  - Exocytosis of a 60 kDa protein (calreticulin) from activated hamster oocytes.
AB  - The sp50 protein localized at the acrosomal region of guinea pig sperm was
      suggested to participate in acrosome exocytosis, the acrosome reaction (AR). On
      the other hand, the cortical reaction (CR), also an exocytotic event, occurs
      during egg activation. The aim of the present work was to identify sp50 and also
      to define if sp50 is present in hamster eggs, as well as its location before and
      after CR. Sp50 was identified as calreticulin (CRT), based on: (a) its NH(2)
      terminal amino acid (25 aa) sequence, (b) a cross-recognition of pure sp50 and
      pure CRT with anti-CRT (from Santa Cruz, anti-CRTsc), and anti-sp50 (anti
      sp50/CRT) antibodies, respectively, and (c) that both antibodies revealed a 50
      kDa protein in a Brij sperm extract. On the other hand, CRT presence in eggs was
      positively determined by Western blotting (Wb) using anti-sp50/CRT antibody which
      recognized a 60 kDa protein in the egg extract, and by indirect
      immunofluorescence (IIF), CRT was located in the cortical granules (CG). It was
      defined by a granular pattern and co-localization with mannose, a specific
      carbohydrate of the CG. Additionally, a decrease in CRT concentration occurred in
      eggs after their activation and, in parallel, the protein was revealed in the
      egg's incubation medium. In activated eggs with zona pellucida (ZP), CRT remains
      as a halo in the perivitelline space and around the polar body. From these
      results we suggest that: (1) CRT is present in the CG of non-activated hamster
      eggs, (2) CRT is exocytosed during the CR, in response to egg activation, and (3)
      CRT might participate in the block to polyspermy, together with other CG
      components.

PMID- 11599053
TI  - Evaluation of the Stag3 gene and the synaptonemal complex in a rat model (as/as)
      for male infertility.
AB  - Affected males (as/as) from the mutant TT rat strain are sterile due to
      spermatogenesis impairment with meiotic arrest at the pachytene stage. The as
      locus is on rat chromosome 12, in a region that shows conserved synteny to cM 74
      94 on mouse chromosome 5. Stag3, a new member of the stromalin protein family, is
      expressed specifically in testis and associates to the synaptonemal complex.
      Mouse Stag3 gene has been assigned to cM 78 on chromosome 5. In this study, we
      have characterized the rat Stag3 gene and examined it as a candidate for male
      infertility in as/as rats. The rat Stag3 cDNA is 4181 nucleotides long, contains
      a highly polymorphic hexanucleotide repeat in the coding region, and encodes a
      1256 amino acid protein with 93 and 77% sequence identity to mouse and human
      Stag3 proteins, respectively. No mutations or differences in size or abundance of
      Stag3 mRNA were detected between as/as and control rats, suggesting that Stag3 is
      not responsible for the aspermic phenotype. In addition, immunohistochemistry
      with antibodies against SCP1 and SPC3 proteins suggest that the synaptonemal
      complex structures are not primarily affected in these rats.

PMID- 11599054
TI  - Partial characterization of the factor in theca-cell conditioned medium that
      inhibits the progression of FSH-induced meiosis of bovine oocytes surrounded by
      cumulus cells connected to the membrana granulosa.
AB  - A factor, secreted by theca cells, inhibits FSH induced resumption of meiosis in
      bovine oocytes that are surrounded by cumulus cells which are attached to a piece
      of the membrana granulosa (COCGs). In order to characterize this factor, theca
      cell conditioned medium (CMt) was heat-treated, filtered through a 5 kD spin off
      filter, charcoal treated, chloroform extracted and protease treated. To
      investigate whether the meiosis inhibiting factor produced by theca cells was
      also present in follicular fluid (FF), the same treatments were done with 50%
      bovine follicular fluid (bFF). COCGs, originating from 2 to 8 mm follicles of
      bovine ovaries collected at a slaughterhouse, were cultured in groups of 15 per
      600 microl medium supplemented with 0.05 IU ml FSH for 22 hr at 39 degrees C in a
      humidified atmosphere of 5% CO(2). After culture the oocytes were denuded,
      stained with orcein, and the nuclear status assessed. Heat treatment did not
      affect the meiosis arresting capacity of CMt since a similar proportion of the
      oocytes remained at the GV stage after 22 hr of culture in heat treated CMt as
      compared to the proportion of oocytes in the GV stage after culture in untreated
      CMt. Filtering through a 5 kD spin-off filter revealed that the meiosis
      inhibiting action was maintained in the <5 kD fraction, although there was a
      significant (P < 0.05) loss of inhibiting activity compared to nonfiltered CMt.
      No significant decrease was observed in the meiosis arresting capacity of the <5
      kD fraction after charcoal or protease treatment. Extraction of the <5 kD
      fraction with chloroform also did not affect the theca cell produced factor. The
      effect of the theca cell factor on the progression of meiosis of the oocytes that
      resumed meiosis, as demonstrated by a very low percentage of the oocytes that
      matured up to the M2 stage, was not affected following any of the treatments.
      With regard to bFF, the results show a lower percentage of the oocytes in the GV
      stage after culture in 50% bFF as compared to culture in CMt, but progression of
      meiosis was clearly inhibited as demonstrated by a significant higher proportion
      of the oocytes blocked in the M1 stage after resumption of meiosis. In general,
      with regard to meiotic inhibition, bFF showed the same pattern as CMt following
      the various treatments. It is concluded that the theca cell secreted factor which
      inhibits the FSH-induced resumption of meiosis in COCGs is a small, stable, polar
      molecule which is not a peptide.

PMID- 11599055
TI  - Effect of antibodies to sperm-specific recombinant contraceptive vaccinogen (rCV)
      on murine fertilization: search for an animal model to examine its contraceptive
      potential.
AB  - Recently, we cloned and sequenced a sperm-specific antigen, designated as
      Contraceptive Vaccinogen (rCV), from human testis (Naz et al., 2001). The present
      study was conducted to examine its proteomic homologue and function in murine
      sperm, in order to find out whether or not the mouse can provide a suitable model
      for examining its immunocontraceptive effects. This was examined by using
      purified antibodies (Ab) raised against the recombinant (r) human CV antigen of
      approximately 44 kD. In the Western blot procedure, rCV antibodies recognized a
      specific protein band of approximately 64 +/- 5 kD in murine testis and murine
      sperm extracts, the band similar to that found in human testis and human sperm.
      In the immunoprecipitation procedure, rCV Ab immunoprecipitated a protein band of
      similar size from murine sperm and murine testis extracts. The immunocytochemical
      (ICT), immunoscanning electronmicroscopic (ISEM) and the immunobead binding
      technique (IBT) revealed the subcellular localization of CV antigen on the
      surface of acrosome and tail regions of the noncapacitated and capacitated murine
      sperm cell. In functional bioassays, rCV Ab inhibited the acrosome reaction as
      well as sperm-egg binding in vitro. These data indicate that the CV antigen is
      expressed in murine sperm and has a biological role in sperm function and sperm
      egg binding. In vitro inhibition of capacitation/acrosome reaction and sperm-zona
      binding suggest that the mouse can provide a suitable model to examine the
      immunocontraceptive effects of CV antigen in actively-immunized animals.

PMID- 11599056
TI  - Capsaicin as a source for painful stimulation in functional MRI.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine the brain
      processing of capsaicin-induced painful stimulation in the alpha-chloralose
      anesthetized rat. Experiments were performed on a 9.4-T magnet (Magnex, UK) with
      Avance console (Bruker, Germany) using a surface coil tuned to 400.5 MHz centred
      over the rat forebrain. Gradient-echo images of two slices, with an echo time of
      25 msec, repetition time of 70 msec, and 50 repetitions, were acquired per
      experiment. These images were analyzed using a fuzzy cluster analysis technique
      (EvIdent). Activation of areas of the brain known to be associated with the
      processing of pain, namely the anterior cingulate (bilateral), frontal cortex
      (bilateral), and sensory motor cortex (contralateral), was found in all animals
      (N = 6) following injection of 25 microl of capsaicin (128 microg/mL in 7.5%
      dimethylsulfoxide [DMSO]) into the dorsal forepaw. It is possible to reproduce
      the pain response in a given animal several times throughout the course of an
      experiment, provided that sufficient time is allowed between capsaicin
      injections. This acute phase of capsaicin-induced pain involving stimulation of C
      polymodal nociceptors was examined by functional imaging. There was a substantial
      initial increase in activation in regions of the brain associated with pain and
      there was a trend towards increasing activation with repeated stimulations.
      Treatment with morphine (3 mg/kg, intravenously) was found to substantially
      reduce, if not completely eliminate, the areas of functional activation
      associated with physiologic pain (anterior cingulate and frontal cortex) after C
      nociceptor stimulation with capsaicin (N = 6). FMRI involving capsaicin-induced
      painful stimulation could prove to be an effective tool for the study of novel
      analgesics and the central nervous system processing of pain.

PMID- 11599057
TI  - Contrast-enhanced coronary MR angiography: relationship between coronary artery
      delineation and blood T1.
AB  - Contrast-enhanced coronary angiography has become an important technique for
      magnetic resonance (MR) coronary artery imaging. However, the relationship
      between the quality of the coronary artery images and blood T1 has not yet been
      fully explored. In this paper, we assessed this relationship in an animal model
      by using a prototypical blood pool agent. With accumulated injections of this
      agent, the blood T1 would be maintained at different levels. The measured blood
      T1 values in vivo were 147 +/- 3, 82 +/- 6, 48 +/- 4, 40 +/- 3, and 30 +/- 8 msec
      (N = 7). Fixed and variable flip angle schemes were used in coronary artery
      imaging. The signal to noise ratios (SNR) of coronary arteries were measured and
      the image quality was assessed. It was found that blood T1 less than 80 msec
      might be desired. No statistically significant difference was observed between
      two flip angle schemes. There was better vessel definition using variable flip
      angle at blood T1 lower than 50 msec. Understanding this relationship may be
      beneficial to optimizing image protocol and/or design of blood pool contrast
      agents for contrast-enhanced coronary angiography.

PMID- 11599058
TI  - Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic
      iron oxide particles.
AB  - Experimental data show accumulation of superparamagnetic iron oxide (SPIO)
      particles in atherosclerotic plaques. SPIO uptake occurred in plaques, suggesting
      an increased endothelial permeability and macrophage infiltrates as signs of
      inflammatory plaque activity. We incidentally observed SPIO uptake in aortic and
      arterial wall segments in patients who had originally received the magnetic
      resonance (MR) contrast agent for staging lymph node metastases. Twenty patients
      (19 male, 1 female; mean age, 64; range, 41-78 years) with bladder or prostate
      cancer underwent MR imaging (MRI) using a T2*-weighted high-resolution gradient
      echo sequence prior to and 24-36 hours after intravenous injection of 2.6 mg of
      Fe/kg of SPIO (Sinerem). The aorta, both common external and internal iliac, as
      well as both superficial femoral arteries, were retrospectively analyzed for
      atherosclerotic wall changes. One patient was excluded. A positive finding was
      defined as an area of pronounced signal loss on postcontrast images clearly
      confined to the arterial wall, which was absent in the precontrast examination or
      increased in size. Such a finding was observed in one to three arteries in 7 of
      the 19 patients. The pronounced signal loss in the wall of the aorta and pelvic
      arteries seen in part of an elderly patient population after intravenous SPIO
      administration strongly suggests that this contrast agent accumulates in human
      atherosclerotic plaques.

PMID- 11599059
TI  - Functional cardiac MR imaging with steady-state free precession (SSFP)
      significantly improves endocardial border delineation without contrast agents.
AB  - Contrast between blood and myocardium in standard turbo gradient echo MR
      techniques (TFE) used routinely in clinical practice is mainly caused by
      unsaturated inflowing blood. Steady-state free precession (SSFP) has excellent
      contrast even in the absence of inflow effects. In 45 subjects cardiac cine loops
      in two long axis projections were acquired using TFE and compared with SSFP. A
      visual score (range 0 worst - 3 best) was assigned for endocardial border
      delineation for six myocardial segments in two long axis views. Endocardial
      border delineation score for TFE was 1.3 +/- 0.3 per segment and 2.4 +/- 0.3 for
      SSFP (P < 0.0001). Signal intensity blood/signal intensity myocardium was 1.5 +/-
      0.4 at enddiastole and 1.4 +/- 0.3 at systole for TFE and 3.5 +/- 1.1 and 3.2 +/-
      1.3 for SSFP, respectively (P < 0.0001). SSFP increases contrast between blood
      and myocardium more than twofold, resulting in an improved endocardial border
      definition. This may reduce variability for the determination of cardiac volumes
      and ejection fraction.

PMID- 11599060
TI  - Adaptive vessel tracking: automated computation of vessel trajectories for
      improved efficiency in 2D coronary MR angiography.
AB  - A new method was investigated for improving the efficiency of ECG-gated coronary
      magnetic resonance angiography (CMRA) by accurate, automated tracking of the
      vessel motion over the cardiac cycle. Vessel tracking was implemented on a spiral
      gradient-echo pulse sequence with sub-millimeter in-plane spatial resolution as
      well as high image signal to noise ratio. Breath hold 2D CMRA was performed in 18
      healthy adult subjects (mean age 46 +/- 14 years). Imaging efficiency, defined as
      the percentage of the slices where more than 30 mm of the vessel is visualized,
      was computed in multi-slice spiral scans with and without vessel tracking. There
      was a significant improvement in the efficiency of the vessel tracking sequence
      compared to the multi-slice sequence (56% vs. 32%, P < 0.001). The imaging
      efficiency increased further when the true motion of the coronary arteries
      (determined using a cross correlation algorithm) was used for vessel tracking as
      opposed to a linear model for motion (71% vs. 57%, P < 0.05). The motion of the
      coronary arteries was generally found to be linear during the systolic phase and
      nonlinear during the diastolic phase. The use of subject-tailored, automated
      tracking of vessel positions resulted in improved efficiency of coronary artery
      illustration on breath held 2D CMRA.

PMID- 11599062
TI  - Impact of bulk cardiac motion on right coronary MR angiography and vessel wall
      imaging.
AB  - The purpose of this study was to investigate the impact of in-plane coronary
      artery motion on coronary magnetic resonance angiography (MRA) and coronary MR
      vessel wall imaging. Free-breathing, navigator-gated, 3D-segmented k-space turbo
      field echo ((TFE)/echo-planar imaging (EPI)) coronary MRA and 2D fast spin-echo
      coronary vessel wall imaging of the right coronary artery (RCA) were performed in
      15 healthy adult subjects. Images were acquired at two different diastolic time
      periods in each subject: 1) during a subject-specific diastasis period (in-plane
      velocity <4 cm/second) identified from analysis of in-plane coronary artery
      motion, and 2) using a diastolic trigger delay based on a previously implemented
      heart-rate-dependent empirical formula. RCA vessel wall imaging was only feasible
      with subject-specific middiastolic acquisition, while the coronary wall could not
      be identified with the heart-rate-dependent formula. For coronary MRA, RCA border
      definition was improved by 13% (P < 0.001) with the use of subject-specific
      trigger delay (vs. heart-rate-dependent delay). Subject-specific middiastolic
      image acquisition improves 3D TFE/EPI coronary MRA, and is critical for RCA
      vessel wall imaging.

PMID- 11599061
TI  - Dobutamine stress cine-MRI of cardiac function in the hearts of adult
      cardiomyocyte-specific VEGF knockout mice.
AB  - A mouse model of non-necrotic vascular deficiency in the adult heart was studied
      using cine-magnetic resonance imaging (MRI) and other techniques. The mice lacked
      cardiomyocyte-derived vascular endothelial growth factor (VEGF) following a
      targeted knockout in the ventricular cardiomyocytes. Quantitative endothelial
      labeling showed that the capillary density was significantly reduced in the
      hearts of knockout mice. Gene expression patterns suggested that they were
      hypoxic. Semiautomated MR image analysis was employed to obtain both global and
      regional measurements of left ventricular function at 10 or more time points
      through the cardiac cycle. MRI measurements showed a marked reduction in ejection
      fraction both at rest and under low- and high-dose dobutamine stress. Regional
      wall thickness, thickening, and displacement were all attenuated in the knockout
      mice. A prolonged high-dose dobutamine challenge was monitored by MRI. A maximal
      response was sustained for 90 minutes, suggesting that it did not depend on
      endogenous glycogen stores.

PMID- 11599063
TI  - Cerebral hemodynamic changes measured by gradient-echo or spin-echo bolus
      tracking and its correlation to changes in ICA blood flow measured by phase
      mapping MRI.
AB  - Changes in cerebral blood flow (CBF) induced by Acetazolamide (ACZ) were measured
      using dynamic susceptibility contrast MRI (DSC-MRI) with both spin echo (SE) EPI
      and gradient echo (GE) EPI, and related to changes in internal carotid artery
      (ICA) flow measured by phase-mapping. Also examined was the effect of repeated
      bolus injections. CBF, cerebral blood volume (CBV), and mean transit time (MTT)
      were calculated by singular value decomposition (SVD) and by deconvolution using
      an exponential function as kernel. The results showed no dependency on
      calculation method. GE-EPI measured a significant increase in CBF and CBV in
      response to ACZ, while SE-EPI measured a significant increase in CBV and MTT. CBV
      and MTT change measured by SE-EPI was sensitive to previous bolus injections.
      There was a significant linear relation between change in CBF measured by GE-EPI
      and change in ICA flow. In conclusion, GE-EPI under the present condition was
      superior to SE-EPI in monitoring cerebral vascular changes.

PMID- 11599064
TI  - The effect of injection rate on time-resolved contrast-enhanced peripheral MRA.
AB  - In contrast-enhanced (CE) magnetic resonance (MR) angiography (MRA), lower
      injection rates of a fixed contrast agent dose provide longer contrast agent
      bolus at the expense of lower intravascular signal. This study evaluated the
      effect of different injection rates in imaging of the vasculature of the lower
      extremities with time-resolved, CE MRA. In three volunteers, injection rates of
      0.5, 1.5 and 3.0 mL/second were administered in a randomized order and imaged in
      two separate sessions. Contrast agent bolus dynamics measured in volunteers were
      used in computer simulations to confirm variations in contrast agent
      concentration as a source of vessel ringing and blurring artifacts. To validate
      the effect of injection rate in pathologic vessels, 37 patients with peripheral
      vascular disease were imaged with a time-resolved technique using an injection
      rate of 0.5 mL/second or 1.5 mL/second and retrospectively divided into two
      groups. In volunteers, higher injection rates caused a stronger modulation of k
      space and resulted in increased ringing artifacts in time-resolved CE MRA. These
      results were reproduced with computer simulations. In the qualitative patient
      study, significantly less vessel blurring was observed using a lower injection
      rate, without a significant loss of vessel contrast.

PMID- 11599065
TI  - Temporal dynamics of blood flow effects in half-Fourier fast spin echo (1)H
      magnetic resonance imaging of the human lungs.
AB  - A cardiac-triggered half-Fourier single-shot turbo spin echo (HASTE) technique is
      currently the method of choice for MR imaging of the lung parenchyma without the
      use of exogenous contrast agents. In this study, we specifically examined the
      effects of the cardiac cycle on the HASTE signal intensity of the lungs. Images
      were obtained from six healthy human volunteers at an end expiration breath-hold
      using a HASTE sequence and a variable cardiac-triggered delay time. Analysis of
      the data sets showed a 30% decrease in the lung signal intensity during systole,
      and a 15% decrease during mid-diastole. These decreases correlate with phases of
      the cardiac cycle when the blood flow in the lungs is expected to be greatest.
      Misregistration artifacts, particularly from the pulmonary arteries and aorta,
      are worse during these periods of signal decrease. To minimize cardiac dependent
      signal losses, HASTE lung imaging should be performed after systole but before
      rapid filling of the ventricles.

PMID- 11599066
TI  - Pulmonary ventilation-perfusion MR imaging in clinical patients.
AB  - The purpose of this study was to evaluate the feasibility of comprehensive
      magnetic resonance (MR) assessment of pulmonary perfusion and ventilation in
      patients. Both oxygen-enhanced ventilation MR images and first-pass contrast
      enhanced perfusion MR images were obtained in 16 patients with lung diseases,
      including pulmonary embolism, lung malignancy, and bulla. Inversion recovery
      single-shot fast spin-echo images were acquired before and after inhalation of
      100% oxygen. The overall success rate of perfusion MR imaging and oxygen-enhanced
      MR imaging was 94% and 80%, respectively. All patients with pulmonary embolism
      showed regional perfusion deficits without ventilation abnormality on ventilation
      perfusion MR imaging. The results of the current study indicate that ventilation
      perfusion MR imaging using oxygen inhalation and bolus injection of MR contrast
      medium is feasible for comprehensive assessment of pulmonary ventilation
      perfusion abnormalities in patients with lung diseases.

PMID- 11599067
TI  - Three-dimensional MR pulmonary perfusion imaging and angiography with an
      injection of a new blood pool contrast agent B-22956/1.
AB  - Initial evaluation of a new blood pool agent, B-22956/1, for pulmonary imaging
      was performed in five domestic pigs with artificial embolism. Pre-embolism 3D
      pulmonary perfusion images were first acquired by injecting an extravascular
      agent, gadoteridol. The pulmonary arteries of the pigs were then occluded by the
      artificial emboli. Post-embolism perfusion scans were subsequently performed by
      injecting B-22956/1. Additional post-embolism high-spatial-resolution angiograms
      were also acquired. Parenchyma perfusion deficits were well depicted in the post
      embolism perfusion maps. The post-embolism angiography clearly revealed the
      location and extent of the filling defects in the pulmonary vessels. Signal
      intensities of perfusion maps on the normal parenchyma were significantly
      improved (30%) by using B-22956/1, in comparison with perfusion images using
      gadoteridol (P < 0.01). Many pulmonary angiograms with approximately equal
      contrast could be obtained even at 22 minutes after the injection of B-22956/1.
      Our initial results indicate that blood pool agent B-22956/1 may provide
      opportunities for whole-lung-coverage perfusion mapping and additional high
      resolution target angiograms after a single injection.

PMID- 11599068
TI  - Menstrual cycle variation of apparent diffusion coefficients measured in the
      normal breast using MRI.
AB  - Recent investigations have shown that tumors may be distinguished from benign
      lesions in the breast based on differences in apparent diffusion coefficient
      (ADC) values. The goal of this study was to assess the magnitude of normal
      variations in the measured ADC of breast parenchyma during the menstrual cycle.
      Eight healthy female subjects were scanned once a week for 4 weeks, using a
      diffusion-weighted single-shot fast spin-echo (DW-SSFSE) sequence. The ADC of
      breast fibroglandular tissue was calculated for each woman at each time point.
      Results showed a trend of decreased ADC during the second week of the cycle, and
      increased ADC during the final week. However, no significant influence of
      menstrual cycle on breast ADC values was identified. The results of this study
      show that the normal fluctuation of breast ADC is relatively small, and the
      coefficient of variation was determined to be 5.5% for our group of volunteers
      during a menstrual cycle. Nonetheless, breast diffusion measurements for tumor
      differentiation and evaluation of treatment response should be interpreted with
      consideration of normal variability.

PMID- 11599069
TI  - Fat-suppressed T2-weighted MRI of the liver: comparison of respiratory-triggered
      fast spin-echo, breath-hold single-shot fast spin-echo, and breath-hold fast
      recovery fast spin-echo sequences.
AB  - The purpose of our study was to compare the value of respiratory-triggered fast
      spin-echo, breath-hold single-shot fast spin-echo, and breath-hold fast-recovery
      fast spin-echo sequences in detecting hepatic lesions. Fat-suppressed T2-weighted
      magnetic resonance (MR) images obtained with the three sequences in 36 patients
      with 138 lesions and nine patients without lesions were prospectively analyzed.
      Quantitative and qualitative analyses, including receiver operating
      characteristic (ROC) analyses, were performed. The mean lesion-to-liver contrast
      to-noise ratio (CNR) for hepatic lesions was highest with the respiratory
      triggered fast spin-echo sequence. On the basis of receiver-operating
      characteristic analyses, tumor detection rates were higher with the breath-hold
      fast-recovery fast spin-echo sequence (Az = 0.94) than with the respiratory
      triggered fast spin-echo sequence (AZ = 0.80, P < 0.0001) or the single-shot fast
      spin-echo sequence (Az = 0.77, P < 0.0001). The image quality with the breath
      hold fast-recovery fast spin-echo sequence was acceptable in all patients. The
      breath-hold fast-recovery fast spin-echo sequence provided the highest tumor
      detection in a short imaging time, although the mean lesion-to-liver CNRs were
      inferior to those of the respiratory-triggered fast spin-echo and the breath-hold
      single-shot fast spin-echo sequences.

PMID- 11599070
TI  - Functional assessment of pancreatic parenchyma after secretin administration
      using serial T2-weighted echo-planar magnetic resonance imaging.
AB  - Signal intensity (SI) changes of pancreatic parenchyma were evaluated after
      intravenous administration of secretin using T2-weighted single-shot spin-echo
      echo-planar imaging (EPI) to assess this method as a magnetic resonance (MR) test
      of pancreatic exocrine function. Nine volunteers were studied with serial single
      shot EPI of the pancreas for 15 minutes after the injection of secretin or
      saline. The normal pattern of pancreatic SI change was demonstrated after
      intravenous injection of secretin, a single peak at 3-4 minutes in the head,
      body, and tail, followed by a gradual decrease in SI. Saline injection did not
      induce a significant SI change. There was no statistical difference in the peak
      contrast ratios (first mean, 1.21-1.25, vs. second mean, 1.18-1.22) and peak
      times (first mean, 3.2-3.7 minutes, vs. second mean, 3.1-3.6) in a repeat study.
      By evaluating the pattern of time-response curves obtained from serial T2
      weighted EPI after secretin injection, pancreatic exocrine function may be
      directly assessed at the level of the head, body, and tail.

PMID- 11599071
TI  - Method for quantitative mapping of dynamic MRI contrast agent uptake in human
      tumors.
AB  - A method is presented for the acquisition and analysis of dynamic contrast
      enhanced (DCE) MRI data, focused on the characterization of tumors in humans.
      Gadolinium (Gd) contrast was administered by bolus injection, and its effect was
      monitored in time by fast T1-weighted MRI. A simple algorithm was developed for
      automatic extraction of the arterial input function (AIF) from the DCE-MRI data.
      This AIF was used in the pixelwise pharmacokinetic determination of physiological
      vascular parameters in normal and tumor tissue. Maps were reconstructed to show
      the spatial distribution of parameter values. To test the reproducibility of the
      method 11 patients with different types of tumors were measured twice, and the
      rate of contrast agent uptake in the tumor was calculated. The results show that
      normalizing the DCE-MRI data using individual coregistered AIFs, instead of one
      common AIF for all patients, substantially reduces the variation between
      successive measurements. It is concluded that the proposed method enables the
      reproducible assessment of contrast agent uptake rates.

PMID- 11599072
TI  - MRI of the foot and ankle: prevalence and distribution of occult and palpable
      ganglia.
AB  - The purpose of this study was to evaluate the prevalence and anatomic
      distribution of occult and palpable ganglia of the foot and ankle as seen by MRI.
      Within a 7-year period MRI of the ankle was performed on 2813 patients, and MRI
      of the foot on 2277 patients using a 1.5T magnet. In all, 167 ganglia in 155
      patients were detected. MR images of these patients were reviewed retrospectively
      by two observers with regard to prevalence, imaging characteristics, and exact
      anatomic location of ganglia. Clinical findings and (when available) surgical
      reports were also reviewed. One hundred fifty-seven ganglia in 145 patients were
      present on MR images of the ankle, and 10 ganglia in 10 patients on MR images of
      the foot, resulting in a prevalence of 5.6% (157/2813) in the ankle, and a
      prevalence of 0.4% (10/2277) in the foot. The most common location was the tarsal
      sinus or tarsal canal (57/167 ganglia [34.1%]). However, only four of these (7%)
      were palpable as a soft-tissue mass. The second most common location was around
      the Lisfranc joint (23/167 [13.8%]), of which 11/23 [47.8%] were clinically
      palpable. Palpable ganglia were statistically larger in size than occult ganglia
      measured in any of three diameters (P = 0.01-0.002). In addition, ganglia of the
      foot and ankle represented 42% of all clinically suspected soft-tissue masses.
      Ganglia in the foot and ankle are an infrequent finding on routine MRI of the
      foot and ankle. When they occur, these ganglia are most frequently located in the
      tarsal sinus and tarsal canal, where they are occult to clinical palpation. If
      ganglia are clinically palpable, they are most commonly located around the
      Lisfranc joint. In addition, palpable ganglia are larger than occult ganglia.

PMID- 11599073
TI  - Safety of metallic implants in magnetic resonance imaging.
AB  - Magnetic resonance (MR) imaging has become a commonly accepted medical procedure.
      Manufacturers of medical implant devices are submitting claims that their devices
      are safe and effective in a MR environment. This paper concentrates on the issue
      of heating of patients due to the interaction of metallic implants with the
      strong radiofrequency (RF) magnetic field produced by the MR scanner. The
      commercially available program XFDTD was used to calculate the specific
      absorption rate (SAR) distribution in a realistic model of the human body. The
      body contained a metallic implant and was exposed to RF magnetic fields at 64 MHz
      from a model of a MR birdcage body coil. The results of the calculation showed
      that the magnitude of the increased heating of tissues due to the presence of the
      metallic implant depended on the dimensions, orientation, shape, and location of
      the metallic implant in the patient. This increased heating of surrounding
      tissues primarily concentrates in a small volume near the tip of the metallic
      wire. When the whole-body SAR was normalized to 1 W/kg, a calculated value of 41
      W/kg was obtained at this location if the absorption was averaged over 1 g of
      tissue. However, a maximum value of 310 W/kg was calculated when the absorption
      was averaged over 1/8 g of tissue.

PMID- 11599074
TI  - Accelerated coronary MRA by simultaneous acquisition of multiple 3D stacks.
AB  - The implementation and first in vivo results of a novel coronary magnetic
      resonance angiography (MRA) protocol allowing simultaneous acquisition of
      multiple geometrically independent 3D imaging stacks are presented. Each imaging
      stack is acquired in a separate cardiac phase using an individual magnetization
      preparation and navigator-based gating and prospective motion correction. Each
      stack covers one of the main coronary vessels. Thus, an improvement of scan
      efficiency was achieved, which was used in this study to reduce total scan time
      at standard image quality. Experiments performed in healthy volunteers and in
      patients using a two-stack approach yielded a total scan time reduction of 50%
      with an image quality equivalent to standard single-stack coronary MRA.

PMID- 11599075
TI  - Effect of body coil electric field distribution on receive-only surface coil
      heating.
AB  - Although in the design of transmit RF coils, B(1) homogeneity is crucial for good
      image quality, discussion of electric field (E-field) distribution in the
      literature has been mostly limited to specific absorption rate (SAR) and patient
      loading (dielectric) effects. In this work, we report on a different aspect of E
      field: the receive-only surface coil heating resulting from the voltage drop
      across the blocking (decoupling) networks and cable traps that are used to
      minimize the transmit field distortion. The results show that the z-component
      (parallel to the coil cable) of the E-field has a significant effect on the
      temperature rise in the surface coil. Therefore, in the receive-only coil
      designs, it is not sufficient to consider only the induced voltage on the coil
      loop due to the B(1) field, as is generally done in blocking network analysis
      calculations. The body coil E-field distribution must be considered as well.

PMID- 11599076
TI  - Neurostimulators: potential for excessive heating of deep brain stimulation
      electrodes during magnetic resonance imaging.

PMID- 11599077
TI  - Study of gas-phase molecular recognition using Fourier transform ion cyclotron
      resonance mass spectrometry (FTICR/MS).
AB  - The application of Fourier transform ion cyclotron resonance (FTICR) mass
      spectrometry to the quantitative study of molecular recognition in the gas phase
      is reviewed. Because most quantitative measurements are dependent on accurate
      determination of the pressure of a neutral reagent, methods for accurate pressure
      measurement in FTICR, including gauge calibration using a reaction with known
      rate constants (the traditional method), exothermic proton transfer rate
      measurement (often the best method when accurate neutral pressures in the
      trapping cell are desired), and linewidth measurement (a little-used, but
      generally applicable method) are discussed. The use of rate constant measurements
      in molecular recognition is illustrated with examples employing natural abundance
      isotopic labeling to study self-exchange and 2 : 1 ligand:metal complex formation
      kinetics in crown ether-alkali cation systems. Self-exchange rates do not
      correlate with alkali cation/crown cavity size relationships, whereas 2 : 1
      complex formation kinetics correlate strongly with size relationships. The use of
      exchange equilibrium constant measurements to characterize molecular recognition
      is illustrated by alkali cation exchanges between 18-crown-6 and the isomers of
      dicyclohexano-18-crown-6. These experiments show that the alkyl-substituted
      ligand binds alkali cations better than unsubstituted 18-crown-6 in the gas
      phase, in accordance with expectations based on the higher polarizability of the
      alkyl-substituted ligand. Further, the metal binding thermochemistry differs for
      the two dicyclohexano-18-crown-6 isomers, with the bowl-shaped cis-syn-cis isomer
      binding all the alkali cations more strongly than the cis-anti-cis isomer. The
      measurement of entropies and enthalpies associated with one of the most subtle
      forms of molecular recognition, enantiomeric discrimination, is illustrated by
      studies of the discrimination between enantiomers of chiral amines by
      dimethyldiketopyridino-18-crown-6. This chiral ligand binds chiral primary
      ammonium cations that have the opposite absolute configuration at their
      stereocenter more strongly than the enantiomer with the same absolute
      configuration. Gas-phase studies show that this enantiomeric discrimination is
      enthalpic in origin, likely related to more favorable pi-pi stacking for the
      preferred enantiomer. Entropy disfavors binding of the preferred enantiomer.

PMID- 11599078
TI  - Mass spectrometry of steroid glucuronide conjugates. II-Electron impact
      fragmentation of 3-keto-4-en- and 3-keto-5alpha-steroid-17-O-beta glucuronides
      and 5alpha-steroid-3alpha,17beta-diol 3- and 17-glucuronides.
AB  - The steroid glucuronide conjugates of 16,16,17-d(3)-testosterone,
      epitestosterone, nandrolone (19-nortestosterone), 16,16,17-d(3)-nortestosterone,
      methyltestosterone, metenolone, mesterolone, 5alpha-androstane-3alpha,17beta
      diol, 2,2,3,4,4-d(5)-5alpha-androstane-3alpha,17beta-diol, 19-nor-5alpha
      androstane-3alpha,17beta-diol, 2,2,4,4-d(4)-19-nor-5alpha-androstane
      3alpha,17beta-diol and 1alpha-methyl-5alpha-androstane-3alpha/beta,17beta-diol
      were synthesized by means of the Koenigs-Knorr reaction. Selective 3- or 17-O
      conjugation of bis-hydroxylated steroids was performed either by glucuronidation
      of the corresponding steroid ketole and subsequent reduction of the keto group or
      via a four-step synthesis starting from a mono-hydroxylated steroid including (a)
      protection of the hydroxy group, (b) reduction of the keto group, (c) conjugation
      reaction and (d) removal of protecting groups. The mass spectra and fragmentation
      patterns of all glucuronide conjugates were compared with those of the
      commercially available testosterone glucuronide and their characterization was
      performed by gas chromatography/mass spectrometry and nuclear magnetic resonance
      spectroscopy. For mass spectrometry the substances were derivatized to methyl
      esters followed by trimethylsilylation of hydroxy groups and to
      pertrimethylsilylated products using labelled and unlabelled trimethylsilylating
      agents. The resulting electron ionization mass spectra obtained by GC/MS
      quadrupole and ion trap instruments, full scan and selected reaction monitoring
      experiments are discussed, common and individual fragment ions are described and
      their origins are proposed.

PMID- 11599079
TI  - Tuning compounds for electrospray ionization/in-source collision-induced
      dissociation and mass spectra library searching.
AB  - Tuning compounds for positive and negative electrospray ionization (ESI) were
      tested for the tuning of in-source collision-induced dissociation (ESI/CID) with
      three types of SCIEX API instruments (API 365, 2000 and 3000) in the single
      quadrupole mode. The vacuum interfaces of these instruments differ slightly in
      geometry, but the principles of ionization and solvent evaporation by nebulizer
      and curtain gases, orifice and skimmer are identical. For comparison of in-source
      CID, breakdown curves of haloperidol, paracetamol, metronidazole and metamizole
      were acquired by increasing the orifice voltages. The API 2000 and 3000 required
      higher orifice voltages than did the API 365 to induce a similar degree of
      fragmentation of the protonated or deprotonated molecules to characteristic
      fragment ions. This increase of orifice voltage could be demonstrated with each
      of the four compounds tested by a shift of the maxima of the breakdown curves to
      higher orifice voltages. A procedure with three collision energy (CE) levels for
      drug identification with a mass spectra library set up with an API 365 therefore
      required an adjustment of the orifice voltages to higher values when being
      transferred to an API 2000 or API 3000. The corresponding orifice voltages for
      the three instruments were 20/50/80 V (API 365), 30/90/130 V (API 2000) and
      40/80/120 V (API 3000). However, a change in orifice voltage of +/-10 V (with the
      API 2000 and 3000) hardly influenced the fit values of a library search for each
      single CE level. For adjusting orifice voltages with different instruments, a
      tuning procedure with haloperidol and paracetamol is presented. With this tuning
      procedure an ESI/CID mass spectra library set up for API 365 and API 150 could
      also be used for drug identification with an API 2000 and an API 3000 with good
      library search results.

PMID- 11599080
TI  - Structural assignment of isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione mono-
      and disulfonic acids by liquid chromatography electrospray and atmospheric
      pressure chemical ionization tandem mass spectrometry.
AB  - Positionally isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione mono- and
      disulfonic acids give rise to similar electrospray ionization (ESI) and
      atmosphere pressure chemical ionization (APCI) mass spectra, which show very
      abundant MH(+) ions and negligible fragmentation. The MH(+) ions of these
      isomeric acids exhibit notably different behavior under collision-induced
      dissociation (CID) conditions. The acids with a sulfonic group at position 8' in
      the quinoline moiety, adjacent to the N-atom, exhibit highly abundant [MH -
      H(2)SO(3)](+) ions (m/z 272 for the mono- and m/z 352 for the disulfonic acids),
      which are of lower abundance in the CID spectra of isomers with the SO(3)H group
      at other positions, remote from the nitrogen atom. The latter isomers undergo
      efficient eliminations of SO(3) and HSO(3). The isomeric diacids with one SO(3)H
      group at position 4 of the indene-1,3(2H)-dione moiety, adjacent to one of the
      carbonyl groups, undergo highly efficient elimination of H(2)O. Mechanistic
      pathways, involving interactions between adjacent groups, are proposed for the
      above regiospecific fragmentations. Pronounced different behavior has been also
      observed in negative ion tandem mass spectrometric measurements of the sulfonic
      acids. The distinctive behavior of the isomeric acids was strongly pronounced
      when the measurements were performed with an ion trap mass spectrometer (LCQ),
      and much less so with a triple-stage quadrupole instrument (TSQ).

PMID- 11599081
TI  - Identification of adulteration in milk by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - The development is described of a rapid, simply and accurate analytical method
      aimed at evaluating both the presence of cow milk in either raw ewe and water
      buffalo milk samples employed in industrial processes and the addition of
      powdered milk to samples of fresh raw milk, using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). The
      presence of adulteration is defined by evaluating the protein patterns coming
      from the most abundant whey proteins, alpha-lactalbumin and beta-lactoglobulin,
      used as molecular markers. As no pretreatment of the milk samples is required and
      owing to the speed and ease of use of MALDI-MS the proposed analytical protocol
      can be used as a routine strategy for the identification of possible adulteration
      of the raw fresh milk samples that the dairy industry receives from producers
      every day.

PMID- 11599082
TI  - Charge-reduced nano electrospray ionization combined with differential mobility
      analysis of peptides, proteins, glycoproteins, noncovalent protein complexes and
      viruses.
AB  - This study explores the potential of a novel electrospray-based method, termed
      gas-phase electrophoretic mobility molecular analysis (GEMMA), allowing the
      molecular mass determination of peptides, proteins and noncovalent biocomplexes
      up to 2 MDa (dimer of immunglobulin M). The macromolecular ions were formed by
      nano electrospray ionization (ESI) in the 'cone jet' mode. The multiple charged
      state of the monodisperse droplets/ions generated was reduced by means of bipolar
      ionized air (generated by an alpha-particle source) to yield exclusively singly
      charged positive and negative ions as well as neutrals. These ions are separated
      subsequently at atmospheric pressure using a nano differential mobility analyzer
      according to their electrophoretic mobility in air. Finally, the ions are
      detected using a standard condensation particle counter. Data were expressed as
      electrophoretic mobility diameters by applying the Millikan equation. The
      measured electrophoretic mobility diameters, or Millikan diameters, of 32 well
      defined proteins were plotted against their molecular weights in the range 3.5 to
      1920 kDa and exhibited an excellent squared correlation coefficient (r(2) =
      0.999). This finding allowed the exact molecular weight determination of large
      (glyco)proteins and noncovalent biocomplexes by means of this new technique with
      a mass accuracy of +/-5.6% up to 2 MDa at the femtomole level. From the molecular
      masses of the weakly bound, large protein complexes thus obtained, the binding
      stoichiometry of the intact complex and the complex stability as a function of
      pH, for example, can be derived. Examples of specific protein complexes, such as
      the avidin or catalase homo-tetramer, are used to illustrate the potential of the
      technique for characterization of high-mass biospecific complexes. A discussion
      of current and future applications of charge-reduced nano ESI GEMMA, such as
      chemical reaction monitoring (reduction process of immunglobulin G) or size
      determination of an intact virus, a supramolecular complex, and monitoring of
      partial dissociation of a human rhinoviruses, is provided.

PMID- 11599083
TI  - An intelligent data acquisition system for simultaneous screening of microsomal
      stability and metabolite profiling by liquid chromatography/mass spectrometry.
AB  - This paper describes the development of a mass spectrometer-based, intelligent,
      programmable, sample-selection data acquisition system with two unique features.
      One is that the system allows automatic determination of the mass to charge ratio
      (m/z) of an unknown compound and the utilization of the molecular ion information
      to perform selective ion monitoring (SIM) experiments for quantitation. The other
      is its decision-making capability to select intelligently different samples and
      perform different experiments during data acquisition. These features were
      demonstrated by the application of the system to simultaneous screening for the
      microsomal stability and metabolite profiling of adatanserin. In this
      application, the data acquisition system continuously calculated the peak areas
      of adatanserin from SIM analyses of a batch of microsomal incubates stopped at
      various time points. Once the peak area of adatanserin had dropped to an
      arbitrarily predefined 60% of the initial value, the system made a decision to
      perform metabolite profiling of the sample. This decision initiated a series of
      automated operations, such as selecting a sample for re-analysis, changing the
      data acquisition time and liquid chromatographic gradient and switching the SIM
      mode to the data-dependent product ion scanning mode. The completed analysis of
      the batch of samples provided information both on the microsomal stability and on
      the metabolic profile of adatanserin. This simultaneous approach to investigating
      microsomal stability and metabolite profiling significantly increases the
      throughput for drug discovery support.

PMID- 11599085
TI  - Gas-phase conversion of tetrazoles to oxadiazoles: isolation and characterization
      of the N-acylated intermediate.
AB  - The 5-substituted tetrazole ring was reacted in the gas phase with an acyl ion
      generated as the secondary reactive chemical ionization plasma in the mass
      spectrometer. The product ions obtained, among others, were proposed as the
      rearranged 2,5-disubstituted-1,3,4-oxadiazole nucleus. Its structure was
      demonstrated by comparison of the product ion spectrum of the 2,5-disubstituted
      1,3,4-oxadiazole derivative obtained by condensed-phase reaction and the product
      ion spectrum of the oxadiazole derivative generated in situ by reaction of the 5
      substituted tetrazole derivative with the acyl plasma. It was proposed that the
      mechanism of this transformation involved the presence of an acylated tetrazole
      intermediary, which could not be isolated in the condensed phase, followed by the
      rearrangement, with nitrogen loss, to afford the oxadiazole derivative. Under our
      conditions we were able to isolate the intermediate ion in the first field free
      region and demonstrate its structure by collision induced dissociation-tandem
      mass spectrometry.

PMID- 11599084
TI  - A fast atom bombardment and matrix-assisted laser desorption/ionization mass
      spectrometry study of doubly charged porphyrins.
AB  - In this mass spectrometry (MS) study of doubly charged porphyrin salts, fast atom
      bombardment (FAB) and matrix-assisted laser desorption/ionization (MALDI) MS
      techniques are utilized to examine several unique ionic species. The predominant
      transformation of preformed doubly charged ions in the desorption/ionization
      mechanism of FAB and MALDI is the result of deprotonation reactions to form
      singly charged ions of the type [M(2+) - H(+)](+) and of one-electron reductions
      to form radical cations [M(2+) + e(-)](+.). The dependence of this phenomenon and
      the formation of a number of additional ionic species on the different matrices
      and the FAB-matrix additive benzoquinone is examined. The significant analogous
      behavior of doubly charged porphyrins in FAB- and MALDI-MS leads to the
      conclusion that one-electron reductions are of distinct relevance in the
      desorption/ionization mechanism of MALDI.

PMID- 11599087
TI  - Current literature in mass spectrometry.

PMID- 11599101
TI  - Absence of SV-40 large T antigen (Tag) in malignant mesothelioma effusions: an
      immunocytochemical study.
AB  - Simian Virus 40 (SV 40) was recently implicated in the pathogenesis of malignant
      mesothelioma. The oncogenic capacity of SV-40 is a function of a nuclear protein,
      the large T antigen (Tag). SV-40 Tag DNA sequences are detected by the polymerase
      chain reaction in 40-80% of malignant mesothelial proliferations. However, the
      role of immunohistochemistry (IHC) in demonstrating the nuclear localization of
      Tag is controversial. We sought to determine the clinical utility of SV-40 Tag
      IHC in pleural effusion cytology as an ancillary tool in the cytologic diagnosis
      of malignant mesothelioma (MM). Formalin-fixed, paraffin-embedded cell block
      sections from 100 pleural effusions (32 MMs, 25 benign reactive, 43 metastatic
      adenocarcinomas) were immunostained for the SV-40 anti-Tag, using two primary
      monoclonal SV-40 Tag antibodies: clone Pab 416 and clone Pab 101. Despite strong
      and consistent immunoreactivity in positive controls, no nuclear immunostaining
      was observed in any case. We believe the small sample size in cytology cell block
      sections, the low viral copy number in infected cells, and the effect of formalin
      fixation may have resulted in absence of immunoreactivity. The role of SV-40 Tag
      IHC in diagnostic cytopathology remains unclear unless further studies reliably
      show its detection.

PMID- 11599102
TI  - T-cell subtypes in bronchoalveolar lavage fluid and in peripheral blood from
      patients with primary lung cancer.
AB  - The changes in local immunology play an important role in lung cancer
      development. We used bronchoalveolar lavage fluid (BALF) and peripheral blood
      (PB) for the analysis of cell profiles in patients with primary lung cancer.
      Twenty-one patients with confirmed primary lung cancer and 13 healthy volunteers
      were investigated. All persons were smokers. The analysis of T-cell subsets was
      performed with a flow cytometry method and with the following antibodies: anti
      CD3, CD4, CD8, CD16, CD25, CD45, CD56, and HLA-DR. We found differences in the
      proportion of lymphocytes between BALF and PB, and a higher proportion of T cells
      and a lower proportion of B and natural-killer (NK) cells in BALF. There was a
      significant difference in the proportion of T-cytotoxic/suppressor lymphocytes,
      which was elevated in the BALF of patients and decreased in patients' PB. The T
      helper:T-cytotoxic/suppressor (Th:Tc/s) ratio was significantly lower in the BALF
      of patients. These changes were visible in patients with a small cell type. The
      percentage of T cells with the alpha chain of receptor to IL-2 (IL -R) was lower
      in the BALF of patients than in the control group. Our observations reflect local
      changes in lung environment in patients affected with lung cancer.

PMID- 11599103
TI  - Detection of monocyte/macrophage cell populations in effusions: a comparative
      study using flow cytometric immunophenotyping and immunocytochemistry.
AB  - The objective of the present study was to compare the efficiency of
      immunophenotyping using flow cytometry (FCM) and immunocytochemistry (ICC) in the
      detection of macrophages in serous effusions. Cytoblock sections from 90
      effusions were stained for the monocyte/macrophage marker CD14, using ICC. Fresh
      frozen samples of all cases were analyzed for CD14 expression, using FCM.
      Epithelial, lymphoid, and mesothelial cell populations were identified using
      antibodies against Ber-EP4, CD45, and N-cadherin, respectively. Results were
      compared with clinical parameters and morphological diagnosis. Thirty-nine
      specimens were cytologically diagnosed as malignant, containing tumor cells of
      nonhematologic origin, whereas 46 were interpreted as benign. Two additional
      specimens were diagnosed as indeterminate or suspicious for malignancy, and 3
      specimens contained lymphoma cells. CD14-positive cells were detected in 85/90
      (94%) of effusions using FCM, and in all 90 specimens using ICC. The percentage
      of CD14-positive cells was highly variable, but in some specimens was as high as
      76% using FCM and 85% using ICC. A good association was observed between the two
      methods in the detection of CD14-positive cells (P < 0.001). The presence of
      macrophages in effusions showed an association with female gender, using both FCM
      (P = 0.002) and ICC (P = 0.011), but none with effusion site, patient age,
      clinical and cytological diagnosis, or presence of Ber-EP4-positive cells (P >
      0.05). The presence of Ber-EP4-positive cells showed a strong association with
      the cytological diagnosis of malignancy (P < 0.001). In conclusion, macrophages
      are a significant cell population in effusions, of both benign and malignant
      etiology, due to both their size and their possible confusion with cancer cells.
      Both FCM and ICC aid in the recognition of these cells, and thus provide an
      effective tool for the identification of different cell populations in effusions.

PMID- 11599104
TI  - Fine-needle aspiration cytology of Kikuchi's lymphadenitis: a report of ten
      cases.
AB  - The purpose of this study was to evaluate the cytologic features of Kikuchi's
      lymphadenitis (KL). Smears from 10 patients with histologically proven KL were
      reviewed. In all cases, fine-needle aspiration (FNA) was performed prior to
      biopsy. To assess the validity of morphologic recognition, a blinded study,
      including smears from non-Hodgkin's lymphomas, nonspecific, and mycobacterial
      lymphadenitis was performed. At least 5 cases showed characteristic cytologic
      findings that permitted their specific recognition. A polymorphous lymphoid
      population with abundant karyorrhectic debris and histiocytes, many of which
      showed a small size and eccentrically placed, crescent nuclei, were
      characteristic features of KL. The remaining 5 cases failed to show typical
      findings and were indistinguishable from other nonspecific, reactive
      lymphadenopathies. When typical cytologic findings are present in an adequate
      clinical context (cervical nodes in young patients), a precise diagnosis is
      possible, avoiding unnecessary biopsies.

PMID- 11599105
TI  - Pitfalls in TRAP assay in routine detection of malignancy in effusions.
AB  - Telomerase has been found to be reactivated in a majority of cancers but is
      inactive in most somatic cells. Our principal goal was to determine the potential
      use of the telomeric repeat amplification protocol (TRAP) assay as marker for
      malignancy in cytological effusions. The simple selection criterion was the
      cytological diagnosis, and routine samples were classified into malignant (58
      samples) and nonmalignant (233 samples). Of the malignant samples, 44/58 (76%)
      were positive by TRAP assay. Of the 14 telomerase-negative cytology-positive
      samples, RNA integrity was poor in 9, indicating suboptimal sample conservation
      for molecular analysis. In 3 of the remaining 5 samples with a negative TRAP
      assay, a high number of malignant cells was observed, and these cells might have
      been telomerase-negative. Thus, the sensitivity of TRAP assay for the presence of
      malignant cells was about 76%. In the cytologically nonmalignant effusions, the
      presence of telomerase activity was observed in 24% (55/233). Of these, 6% were
      highly suspicious for malignancy, 9% were doubtful, and 9% were cytologically
      nonmalignant effusions confirmed by a follow-up of 12 mo or more. According to
      these data, the specificity of the TRAP assay to detect tumor cells in effusions
      ranged only between 82-91%. Our results indicate that, although the TRAP assay is
      positive in 6-15% of putative malignant effusions, the relatively high number of
      TRAP false-negative and false-positive cases renders this test unsuitable for
      routine diagnostic purposes.

PMID- 11599106
TI  - Interinstitutional review of thyroid fine-needle aspirations: impact on clinical
      management of thyroid nodules.
AB  - Routine interinstitution pathology consultation can result in change in
      pathologic diagnosis in up to 10% of patients. In this study, we compared the
      outside cytopathologic diagnosis of thyroid fine-needle aspiration (FNA)
      specimens with the in-house diagnosis at the University of Pennsylvania Medical
      Center over an 18-mo period and its effect on patient management. One hundred ten
      (60%) diagnostic disagreements were identified among 183 patients. In 16 cases,
      the diagnosis was changed from benign to malignant, and in 12, the diagnosis was
      reversed from neoplastic/malignant to benign. Histologic follow-up was available
      in 109 cases; the overall accuracy of outside diagnosis was 73%, and that of
      inside diagnosis was 85%. In conclusion, we strongly recommend interinstitution
      cytology consultation on referred thyroid FNA cases, since our data showed a
      significant change in diagnosis, thus affecting patient management.

PMID- 11599107
TI  - Clinical relevance of benign endometrial cells in postmenopausal women.
AB  - Our objective was to determine if the finding of benign endometrial cells on a
      Papanicolaou (Pap) smear of a postmenopausal woman is associated with
      endometrial/uterine pathology, independent of symptomatology and hormone
      replacement therapy (HRT) status. The medical records of 146 postmenopausal
      patients who had a Pap smear showing normal-appearing endometrial cells between
      January 9, 1997 and January 12, 2000 were reviewed. Uterine pathology for each
      patient was determined by reviewing the results of endometrial sampling
      (endometrial biopsy or dilatation and curettage), hysterectomy, or pelvic
      sonogram, which were performed within 24 mo of the cytologic smear. The results
      were then correlated with clinical symptomatology and HRT status of each patient
      at the time the cytologic smear was obtained. Of the 146 Pap smears coded with
      "endometrial cells in a postmenopausal woman," 50 were excluded due to prior
      hysterectomy, perimenopausal status, and absence of further follow-up. Of the
      remaining 96 women, 27 (28%) had benign pathologic findings including polyps,
      leiomyomata, and simple hyperplasia without atypia, whereas 11 (12%) had
      significant pathologic findings including hyperplasia with atypia,
      adenocarcinoma, mixed Mullerian tumor, and leiomyosarcoma. Of the 11 patients
      with significant pathology, only one patient did not have abnormal vaginal
      bleeding but instead had a 30-wk-size irregular uterus on examination, and only 2
      patients received hormone replacement therapy. In conclusion, Reporting
      endometrial cells on Pap smears in postmenopausal women did not lead to the
      diagnosis of any cases of significant pathology that would have gone unsuspected
      clinically. Moreover, HRT status did not affect the incidence of normal
      endometrial cells on Pap smears in postmenopausal women, nor did it aid in
      distinguishing which postmenopausal women had endometrial/uterine pathology. This
      calls into question the usefulness of the current Bethesda guideline to report
      "benign endometrial cells in a postmenopausal woman."

PMID- 11599108
TI  - Cytological diagnosis of primary leiomyosarcoma of bone: case report.
AB  - We report on a case of primary leiomyosarcoma of the bone in a 77-yr-old man. The
      patient presented with a painful, enlarging mass in the left shoulder of 6 mo
      duration. Radiography and computed tomography (CT) revealed a large destructive
      intramedullary lesion of the proximal humerus, with massive extension into the
      surrounding soft tissues. CT-guided fine-needle aspiration biopsies (FNAB) of
      both the bony and soft-tissue lesions were performed. Cytological examination
      showed a neoplastic process composed of spindle cells mixed with pleomorphic
      cells. The smooth muscle origin of the neoplastic cells was confirmed by
      immunocytochemical analysis. We describe the cytological features of this rare
      primary tumor of bone, and consider the differential diagnosis of spindle-cell
      neoplasms.

PMID- 11599109
TI  - Rhinosporidiosis of the parotid duct cyst: cytomorphological diagnosis of an
      unusual extranasal presentation.
AB  - This cytology report highlights a case of rhinosporidiosis of the parotid duct
      cyst not associated with nasal manifestations. In an endemic area, one should be
      familiar with its morphologic features in fine-needle aspiration cytology even on
      scanty material, for it could be one of the investigations in the initial workup
      of a case.

PMID- 11599110
TI  - Serous fluid cytology as a means of detecting hemophagocytosis in Epstein-Barr
      virus-induced autoimmune hemolytic anemia.
AB  - The case of a 22-yr-old male who after a brief febrile episode developed
      autoimmune hemolytic anemia and right pulmonary infiltrate with pleural effusion
      is presented. Cytologic examination of the pleural fluid revealed lymphocytosis
      and hemophagocytosis, primarily of red blood cells (RBCs) by mature histiocytes.
      There was accompanying splenomegaly, laboratory evidence of hepatic dysfunction,
      and retroperitoneal lymphadenopathy. Besides profound reduction of red blood
      cells in the peripheral blood, there was reduction of lymphocytes and platelets.
      As a neoplastic process was ruled out by bone marrow and pleural biopsies, the
      disease was considered to be virus-induced and was halted and progressively
      regressed with early institution of vigorous antiinflammatory therapy with
      adrenocortical steroids. Upon reviewing the case, examination of the bone marrow
      biopsy disclosed limited hemophagocytosis of RBCs and lymphocytes by histiocytes
      and considerable viral cytopathic effect on hematopoietic cells (red and white
      cell precursors and megakaryocytes), which by appropriate immunolabelling was
      identified as induced by Epstein-Barr virus. A virus-related acquired
      hemophagocytic syndrome in its early stages was probably present, yet an
      undesirable clinical outcome was averted by early institution of vigorous steroid
      therapy. The need to recognize early hemophagocytic changes in cytologic
      specimens for early institution of appropriate therapy is emphasized. The
      possibility of erythrophagocytosis, also manifested during the course of an
      autoimmune hemolytic process and unrelated to hemophagocytic syndrome, is
      discussed.

PMID- 11599111
TI  - Lobular carcinoma with cytoplasmic granules.
AB  - We report on a case of invasive lobular carcinoma of the breast with a previously
      undescribed cytologic feature. Diff-Quik-stained cytologic preparations showed
      uniform single cells with prominent coarse cytoplasmic granules.
      Ultrastructurally, the granules showed features suggestive of autophagosomes
      and/or degenerative mitochondria. The cytologic differential diagnosis included
      granulocytic sarcoma, metastatic melanoma, extramedullary hematopoiesis, large
      granulocytic leukemia/lymphoma, and mast-cell tumor. Adjunctive studies were
      helpful in the diagnosis of carcinoma. Histologic study of the mastectomy
      specimen showed classic type of invasive lobular carcinoma.

PMID- 11599112
TI  - Tophaceous pseudogout: a pitfall in the diagnosis of chondrosarcoma.
AB  - Tumoral calcium pyrophosphate dihydrate deposition disease (TCPPD, tumoral or
      tophaceous pseudogout) is a rare nonneoplastic entity which mimics soft-tissue or
      skeletal malignancy. We present here the fine-needle aspiration cytology findings
      of a unique case of TCPPD in a 76-yr-old woman, with a large paraischial soft
      tissue mass diagnosed as a malignant neoplasm. The difficulty in diagnosing such
      lesions by fine-needle aspirates is discussed and reviewed in the context of
      known cases from the literature.

PMID- 11599113
TI  - Specialized preparative devices are not needed for liquid-based, thin-layer
      cytology: an alternate manual method using a metastable alcoholic gel.
AB  - The blending and use of a metastable alcoholic gel is described. The gel creates
      durable, uniform suspensions of cells and small aggregates of cells. It allows
      the random, uniform transfer of virtually any liquid-fixed cytology specimens to
      a glass slide without the use of specialized devices, proprietary disposables, or
      adhesive-coated glass slides. The method is inexpensive and can be performed in a
      timely fashion, not impacting laboratory turnaround times or requiring the
      specimen to be processed by other laboratories. It empowers cytology laboratories
      of any size or level of complexity to make slides from readily available
      commercial cytology fixatives. It allows the total contents of liquid-based
      cytology specimen vials to be examined, providing a "cytological method" for
      quality assuring liquid-based cytology samples.

PMID- 11599114
TI  - Outcomes of cytopathology studies presented at national pathology meetings.
AB  - The purpose of this study was to determine what factors influence the final
      publication status of cytopathology studies presented at national meetings.
      Abstracts involving cytopathology material were obtained from the following
      journals: Modern Pathology (volume 11, 1998), Acta Cytologica (volume 42, 1998),
      and the American Journal of Clinical Pathology (volumes 109 and 110, 1998). Using
      the National Library of Medicine Website, each abstract was searched by author
      and topic to determine if the study was published as a peer-reviewed article. The
      following parameters were evaluated: meeting where the abstract was presented,
      type of institution where the research was based, type of material used in the
      study, and application of ancillary techniques used in the study. The subsequent
      published articles were evaluated for journal and time to publication. Out of 257
      studies presented in 1998, 85 (33%) were published in peer-reviewed journals by
      May 2000. The majority of papers were published in Diagnostic Cytopathology (n =
      21), Acta Cytologica (n = 15), and Cancer (n = 18). The mean time for publication
      was 12.8 mo. The highest percentage of published studies was presented at the
      United States and Canadian Academy of Pathology (USCAP) meeting (50% of presented
      abstracts), followed by American Society of Cytopathology (ASC) (28%) and
      American Society of Clinical Pathologists (ASCP) (17%) meetings. Ancillary
      techniques were applied in 40 of 85 (47%) published studies, 27 of 85 (32%)
      articles focused on morphology, and 18 of 85 (21%) papers covered other topics
      (e.g., quality assurance (QA), cost, and role of cytology). In nonpublished
      studies (n = 172), special techniques were the main focus in 40%, morphology in
      25%, and other topics in 35% of abstracts. The great majority (97%) of published
      studies were from academic institutions. Gynecological and nongynecological
      material were roughly equally covered in published and nonpublished studies. Only
      a relatively small percentage of presented studies was finalized in the form of
      peer-reviewed articles. Type of material and application of ancillary techniques
      do not significantly influence the outcome.

PMID- 11599116
TI  - Is lab automation right for your lab?

PMID- 11599115
TI  - Usefulness of concurrent Papanicolaou smear at time of cervical biopsy.
AB  - The reliability and cost-effectiveness of a repeat Papanicolaou (Pap) smear
      performed at the time of colposcopic biopsy is uncertain. To evaluate the
      usefulness of this practice, Pap smear and biopsy results of 718 patients were
      reviewed and compared: 619 patients had Pap smears performed prior to colposcopy
      with a 1.1% false-negative rate, 97.5% sensitivity, and 83.6% positive predictive
      value. Ninety-nine patients had Pap smears performed at the time of colposcopy
      with a 19.1% false-negative rate, 56.8% sensitivity, and 92.6% positive
      predictive value. Repeat Pap smear at the time of colposcopy resulted in
      significant changes in the management of only 2 patients (2%) and more careful
      follow-up in one (1%). Pap smears performed at colposcopic biopsy are less
      sensitive than those done prior to biopsy (P < 0.001). The clinical benefit of
      this practice is marginal, considering the added costs and potential detrimental
      effects to the colposcopic examination, provided patients receive adequate follow
      up.

PMID- 11599117
TI  - Picturing tomorrow's system.

PMID- 11599118
TI  - Fighting 'alphabet blight'.

PMID- 11599119
TI  - How the smaller chemistry analyzers stack up.

PMID- 11599120
TI  - More reliable minority ethnic population estimates and proportions for local
      areas: which areas to select and other choices to be made--an exploratory
      analysis.
AB  - Central and Local Government and other organisations are interested, for a
      variety of purposes, in obtaining better--more reliable--estimates of the
      proportions of the total populations in local authority districts which belong to
      the minority ethnic population. In inter-censal periods, this aim could be met,
      for example, by an increase in the size of the Labour Force Survey sample in
      selected areas. This article considers the optimal sample size for each area
      under different criteria to improve the reliability of its estimated minority
      ethnic proportion.

PMID- 11599121
TI  - The dynamics of living arrangements in later life: evidence from the British
      Household Panel Survey.
AB  - Living arrangements are a key dimension of quality of life and well-being in old
      age. Availability of family care, as well as social and economic support, is in
      part a function of whom you live with. In order to be able to forecast future
      changes in household composition, particularly in relation to planning and
      targeting particular community care services, information is needed on the
      probability of a person experiencing a change in their living arrangements, and
      the life course events that may act as triggers for such changes. This article
      uses data from the British Household Panel Survey (1991-99) to analyse the
      dynamics of living arrangements in later life.

PMID- 11599122
TI  - Assumptions for the 2000-based national population projections.
AB  - This article summarises the long-term assumptions of fertility, mortality and net
      migration which will underlie the forthcoming 2000-based national population
      projections. Compared with the current (1998-based) projections, the new
      projections will assume lower levels of fertility, but higher levels of inward
      net migration. There will be relatively little change to mortality assumptions.
      Results of the new projections will be available on 15 November 2001.

PMID- 11599123
TI  - The sizes and characteristics of the minority ethnic populations of Great Britain
      -latest estimates.
AB  - This article presents estimates of the minority ethnic populations of Great
      Britain in 2000 and describes the regional distributions of the different groups.
      It also discusses changes in the sizes of the different minority ethnic
      populations during the 1990s. The paper provides information on some key
      demographic features of these populations at the end of the 1990s--age and sex
      structures, proportions born in the United Kingdom and whether children lived
      with their natural parents.

PMID- 11599125
TI  - Prenatal ionizing radiation-induced apoptosis of the developing murine brain with
      special references to the expression of some proteins.
AB  - Apoptosis induced by ionizing irradiation of the developing mouse brain was
      investigated by using histology, analysis of DNA fragmentation on agarose gel and
      electron microscopy. A TUNEL-labeled index (L.I.) was calculated from the
      terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling
      (TUNEL) assay in 4 specific regions, cortical plate, intermediate zone,
      subependymal zone, and subependymal germinal matrix. The kinetics of apoptosis
      associated protein was examined by western blotting and immunofluorescence.
      C57BL/6J mice pregnant on embryonic day 14 (E14) were exposed to a single dose of
      1.5-Gy irradiation. Irradiated fetal brains at E15 and E17 showed extensive
      apoptosis with morphological characteristics. In all 4 regions, L.I. was greater
      in irradiated brains than in control brains at E15 and E17. Most of TUNEL-labeled
      cells expressed a mature neuronal marker (NeuN) and Bax protein, which is up
      regulated in irradiation-induced apoptosis. Ionizing radiation moderately
      enhanced expression of Bax, Bcl-xL, and Cpp32 proteins. Postnatal irradiated mice
      showed microencephaly as compared to age-matched mice and the weight of whole
      body including brain decreased moderately.

PMID- 11599124
TI  - Heparin and heparan sulfate inhibit extracellular signal-regulated kinase
      activation and myocardial cell hypertrophy induced by endothelin-1.
AB  - Heparan sulfate (HS) is one of the components of extracellular matrix and a
      potent anti-growth factor in various cells. Heparin has a similar structure to HS
      and is demonstrated to inhibit myocardial cell hypertrophy. We examined the
      intracellular signal mechanisms linking to the inhibitory effects of heparin and
      HS on endothelin-1 (ET-1)-induced hypertrophy in cultured rat neonatal myocardial
      cells (MCs). Heparin inhibited ET-1-induced c-fos mRNA expression. Heparin and HS
      inhibited ET-1-induced activation of c-fos promoter/enhancer in MCs. Although
      heparin and HS inhibited ET-1-induced activation of the wild-type c-fos serum
      response element (SRE), the activation of a mutated c-fos SRE that contains an
      intact binding site for the serum response factor (SRF) but lacks the ternary
      complex factor (TCF) binding site, was not inhibited. In addition, heparin and HS
      inhibited the activation of TPA response element (TRE). However, heparin did not
      inhibit the activation of cyclic AMP response element (CRE). Furthermore, heparin
      and HS inhibited ET-1-induced activation of extracellular signal-regulated kinase
      (ERK) and phosphorylation of Elk-1, which is one of the TCFs. These results
      indicate that heparin and HS inhibited ET-1-induced ERK activation, resulting in
      suppression of Elk-1 phosphorylation, and lead to inhibition of c-fos gene
      expression through SRF-independent manner. Moreover, heparin and HS inhibited ET
      1-induced [3H] leucine incorporation. These results suggest that heparin and HS
      inhibit ET-1 induced myocardial cell hypertrophy through the inhibition of gene
      expression and protein synthesis.

PMID- 11599126
TI  - Induction of heat shock proteins and its effects on glial differentiation in rat
      C6 glioblastoma cells.
AB  - Heat shock proteins (HSPs) are immediately expressed in neuronal and glial cells
      under various stressful conditions and play a protective role through molecular
      chaperones. We investigated the characteristics of the induction manner of heme
      oxygenase-1 (HO-1) and HSP70 in rat C6 glioblastoma cells. In heat treatment (42
      degrees C for 30 min), C6 cells expressed high level of HO-1 and HSP70 mRNAs
      within 30-60 min, and their proteins at 3 hrs. Heat-induced expressions of HSPs
      mRNAs were completely inhibited with actinomycin D, suggesting the
      transcriptional regulation. Oxygen-glucose deprivation (OGD), cystine-free
      (inhibition of synthesis of glutathione), cyto-toxic (ethanol, sodium butyrate)
      treatments resulted in different expression manners between HO-1 and HSP70, which
      suggested that HO-1 and HSP70 play different protective roles against a variety
      kind of stressful conditions in glial cells. C6 cells can differentiate toward
      both astrocyte and oligodendrocyte directions. Treatment with dibutyryl cyclic
      AMP (cAMP) induces expression of glial fibrillary acidic protein (GFAP), a marker
      of astrocytes, and treatment with retinoic acid (RA) induces expression of myelin
      proteolipid protein (PLP), a marker of oligodendrocytes, respectively. Heat
      treatment before the initiation of differentiation by RA reduced the RA-induced
      expression of PLP mRNA profoundly, but not in GFAP mRNA level induced by cAMP.
      Heat treatment after the initiation of differentiation by cAMP or RA accelerated
      the expression of GFAP or PLP mRNAs. Astroglial differentiation by cAMP reduced
      the heat-induced expressions of HSPs mRNAs, but no change with RA pre-treatment.
      These results suggested that HSPs may modulate the glial differentiation in the
      developing brain. On the contrary, glial differentiation may give influence on
      the stress-induced HSPs expression. The timing of stressful damages, resulting in
      the expression of HSPs, on the developing brain is critically important for the
      pathogenesis of glial lesion. In the heat-treated C6 cells, the expression of
      platelet-derived growth factor (PDGF) receptor-alpha mRNA was significantly
      decreased. HSPs may have ability to induce the glial differentiation in part
      through down-regulation of the PDGF pathway.

PMID- 11599128
TI  - Plasmodium research.

PMID- 11599129
TI  - Progress towards poliomyelitis eradication.

PMID- 11599127
TI  - Suppression of serum starvation-induced apoptosis by hepatitis C virus core
      protein.
AB  - Hepatitis C virus (HCV) core protein either enhances or inhibits apoptosis
      depending on the apoptosis-inducing stimuli and cell conditions. In this paper we
      studied possible effect of HCV core protein on apoptosis induced by serum
      starvation. NIH3T3 cells stably expressing HCV core protein were more resistant
      to serum starvation-induced apoptosis than were the non-expressing control.
      Neither p53, p21Waf1 nor Bax was detectably induced after serum starvation,
      irrespective of HCV core protein expression, suggesting that the observed
      apoptosis is p53-independent. Serum starvation-induced apoptosis was partially
      inhibited by SB203580, a specific inhibitor of p38 mitogen-activated protein
      (MAP) kinase, in the non-expressing control, but not in HCV core protein
      expressing cells. Moreover, activation of p38 MAP kinase after serum starvation,
      as measured by the amount of its phosphorylated form, was inhibited in HCV core
      protein-expressing cells. Our results suggest that HCV core protein inhibits
      serum starvation-induced apoptosis through inhibition of p38 MAP kinase
      activation.

PMID- 11599130
TI  - Service needs of families where one parent has an affective illness: implications
      for service, education, and policy.
AB  - This study explored the service needs of families with a parent with an affective
      illness. Focus-group and individual interviews were conducted at selected
      locations across Canada with individuals who had an affective disorder, their
      partners, and their adult children. A total of 67 participants were recruited.
      Corresponding service providers were mailed a questionnaire which asked
      information regarding these families' needs, the service provider's role with
      these families, and what prevented or assisted them in addressing those needs. A
      total of 419 service providers participated in the study. There was congruence
      between family-identified needs and the needs identified by service providers.
      However, there remains a large disparity between the knowledge of needs and
      having these needs met. The results of this study identify the gaps in service
      provision and make recommendations for changes in the areas of service,
      education, and policy-making.

PMID- 11599131
TI  - The community/privacy trade-off in supportive housing: consumer/survivor
      preferences.
AB  - Supportive housing for psychiatric consumers/survivors can range in form from
      dispersed apartments to group homes. This research asked: What form is more
      supportive, apartments or housing with common spaces? Is it privacy and normalcy
      or community and peer support that promote well-being? The literature is divided.
      This study convened a charrette for supportive housing residents to express their
      views. Some 20 supportive housing residents formed two teams, with one team
      producing a housing design based on the principle of privacy and the other team
      producing one based on the principle of community. Despite their differing terms
      of reference, the teams developed similar designs. The results reinforced the
      importance of both private and common spaces in supportive housing.

PMID- 11599132
TI  - [Games of chance and gambling in adolescents and in adolescents-at-risk].
AB  - A number of studies have established that adolescents are attracted to games of
      chance and gambling, and have confirmed that excessive gambling is not a
      phenomenon of adulthood alone. In Quebec, the proportion of high school students
      who are struggling with gambling problems is estimated at 2.6% (Ladouceur,
      Boudreault, Jacques, & Vitaro, 1999). So far, few researchers have studied
      adolescent populations that are at greater risk of developing gambling problems.
      The present study was carried out among 104 adolescents in difficulty, ranging in
      age from 12 to 19 and served by the Centre jeunesse de Quebec. It assesses the
      prevalence of excessive gambling and the problems associated with it. The results
      indicate that 92.3% of adolescents had bet at least once during the previous year
      and 40.4% bet every week. The prevalence of excessive gambling was established at
      7.7%. Girls were found to gamble as frequently as boys and to experience as many
      gambling problems. In addition, habitual gambling was found to be associated with
      the consumption of psychotropic substances, delinquent behaviour and school
      absenteeism. The discussion puts the results obtained in perspective and
      emphasizes the need for establishing gambling prevention programs among at-risk
      youth.

PMID- 11599133
TI  - [Female victimization in the context of dating violence in adolescence:
      development of an instrument (VIFFA)].
AB  - The aim is to report on the development and preliminary validation of an
      instrument, VIFFA (Violence faite aux Filles dans les Frequentations a
      l'Adolescence), on female victimization in the context of dating violence in
      adolescence. Objectives are twofold: to document the psychometric qualities of
      this self-report and to propose an instrument adapted to the context of young
      teens. The instrument refers to concepts of physical, emotional, and sexual
      abuse. Questioning in two phases is used to achieve proper understanding of the
      concept studied and to help select the partner to whom they refer in the second
      detailed phase. Girls were questioned on violence sustained and boys on violence
      inflicted. The total sample included 331 boys and 377 girls; their mean age was
      14.6 years. A social desirability questionnaire was used to evaluate discriminant
      validity and the results indicate that the adolescents' answers were not
      distorted by social desirability. The factorial analyses resulted in 4 slightly
      different factors for girls and boys. With regard to the girls (violence
      sustained), the factors included Verbal and Emotional Abuse, Physical Abuse,
      Control through Jealousy and Sexual Abuse. With the boys (violence inflicted),
      the factors were Psychological Abuse, Jealousy and Sexual Abuse, Severe Physical
      Abuse and Minor Physical Abuse. Validation studies indicate that the instrument
      has adequate psychometric qualities and is adapted to the context of adolescence.
      An innovative aspect is the place given to items concerning jealousy.

PMID- 11599134
TI  - Community, empowerment, and resilience: paths to wellness.
AB  - In this paper, we explore 3 diverse populations: street kids, political
      prisoners, and caregivers of people with HIV/AIDS. From these explorations, we
      consider the concepts of empowerment, resilience, and community-building. By
      interweaving these 3 key concepts, we develop a cyclical wellness model which can
      be applied equally to individuals and communities. This model highlights the
      strengths of individuals and communities and will, we believe, provide a critical
      element of hope to societies within our increasingly global economy.

PMID- 11599135
TI  - Increasing access and building equity into mental health services: an examination
      of the potential for change.
AB  - This article explores the use of mental health care services by ethnoracial
      people in Canada and distinguishes between the reasons for underutilization of
      services by ethnoracial groups and the barriers which prevent ethnoracial groups
      from accessing services. Research focusing on Canadian race relations is reviewed
      to reveal how they are paralleled in the functioning of mainstream mental health
      care organizations. Existing policies and attitudes are then considered in
      relation to how they support or impede interventions to increase accessibility to
      services. Finally, frameworks for organizational change based on multiculturalism
      and anti-racism are presented, and the advantages and disadvantages of both are
      articulated.

PMID- 11599136
TI  - Community treatment orders: ethical practice in an era of magical thinking.
AB  - With the passage of legislation in June 2000, coercive measures in the form of
      community treatment orders (CTOs) have become part of the community mental health
      landscape in Ontario. Given that community practitioners place a high value upon
      their ability to create voluntary and egalitarian partnerships with clients, the
      question of whether ethical practice is possible under conditions of legislated
      coercion is relevant. Based upon a review of the pro and con arguments that
      preceded CTO legislation, followed by an examination of available research on
      effectiveness, this paper suggests that forms of magical thinking have been at
      work on both sides of the CTO debate. A broader definition of coercion is
      proposed--one that envelopes both overt and covert forms. Finally, the author
      offers an approach to ethical practice which is based on the use of
      transformative power rather than coercive power, and which includes a 3-step
      strategy (using liberation tactics, proactive contracting, and procedural
      justice).

PMID- 11599138
TI  - [The parental practice of psychological violence: a threat to mental health].
AB  - This literature review documents the risk associated with psychologically violent
      parental practices for the well-being and future mental health of youth, with
      regard to 3 aspects: the prevalence of parental practices of this kind, their
      etiological specificities in spite of their co-occurrence with other forms of
      maltreatment, and their potential detrimental impact on young victims. Summing up
      current knowledge about psychological violence, this analysis points out possible
      means of intervention in terms of prevention, screening, and support. However, it
      also calls for caution regarding the use of more intrusive modes of intervention,
      such as child protection.

PMID- 11599137
TI  - [Health professionals in part-time employment: the challenge of balancing work
      and family].
AB  - Looking at the case of occasional part-time nurses, this study highlights the
      difficulties in balancing work and family that are inherent in nonstandard jobs.
      Eight focus groups were held, involving 48 nurses in 4 regions of Quebec.
      Analysis of the data collected reveals that nurses "on call" are particularly
      affected by overwork and experience great difficulty in balancing their work and
      family obligations. The participants proposed a variety of solutions, such as
      establishing day care centres adapted to the needs of nurses on call and
      instituting a timetable grid for occasional part-time nurses so that they can
      plan their work hours.

PMID- 11599139
TI  - [Extra-oral implants: a "new" subject?].

PMID- 11599140
TI  - [From intra-oral implantology to extra-oral implantology].

PMID- 11599141
TI  - [Extra-oral implants: principal areas of implantation].
AB  - The success of extra-oral implants raises a certain number of technical and
      medical problems. Among these, the anatomy of the implant zone and bone quality
      are determining factors for osteointegration of the implants. We describe the
      principal zones of implantation detailing the risks involved in each area.

PMID- 11599142
TI  - [Description and classification of extra-oral implants].
AB  - There is no universal extra-oral implant (EOI) that provides an answer to all
      clinical situations. We present briefly the two main categories of extra-oral
      implants currently available, endo-osseous implants and juxta-osseous implants,
      comparing the advantages and disadvantages of each. We also discuss the new
      developments currently under experimentation in extra-oral implantology.

PMID- 11599143
TI  - [Extra-oral implants: indications and contraindications].
AB  - Osseointegrated facial prostheses are an interesting solution for maxillofacial
      rehabilitation when reconstructive surgery cannot be proposed. Progress in
      epithesis materials and in implantation techniques have renewed interest in
      maxillofacial prostheses. The best indications are for rehabilitation of nasal,
      auricular and orbitopalpebral defects. Another indication is complex loss of
      facial tissue. Endo-osseous epitheses are recommended mainly when there is no
      possibility of reasonable and satisfactory surgical reconstruction, when local
      carcinologic prognosis is uncertain, and to respond to the patient's demands. We
      detail here the precautions necessary when irradiation has been performed
      previously and finally present the contraindications against epitheses on
      osseointegrated implants.

PMID- 11599144
TI  - [Extra-oral implants: surgical procedures].
AB  - The different extra-oral implant systems (screw and plate fixation) are not
      compatible. Rigorous surgical procedure (detailed and illustrated here) is
      mandatory to obtain the best implant osseointegration and epithesis loading 3
      months later. Besides surgical procedure, careful bone and peri-abutment suture
      are required for success.

PMID- 11599145
TI  - [Indications for extra-oral implants: strategic methods apropos of a clinical
      case].
AB  - We report the case of a 73-year-old man with an extensive tumor of the external
      ear, describing the criteria that led us to use an extra-oral implant and not
      reconstructive surgery. Each criteria was evaluated comparatively to another
      option and also on the prosthesis level.

PMID- 11599146
TI  - [Localized loss of facial tissue. Criteria of use of extra-oral implants and
      clinical cases].
AB  - Osseointegrated maxillofacial epitheses are an interesting therapeutic response
      for rehabilitation after loss of facial tissue when reconstructive plastic
      surgery cannot be proposed. We analyzed the criteria used for deciding on this
      type of treatment for the loss of local areas of auricular tissue, the nasal
      pyramid and the orbitopalpebral region, presenting individual clinical examples.

PMID- 11599147
TI  - [The complex facial prosthesis. The value of bone-anchored maxillofacial
      prostheses in the treatment of extensive loss of facial tissue].
AB  - Maxillofacial surgeons are more and more confronted with wide defects of the
      face, particularly after resection of facial cancer. Complex wounds of the face,
      whatever the etiology may be, poses the difficult problem of their
      rehabilitation. The surgical reconstruction offers usually the most interesting
      solutions on the conceptual and morphological stages. There remain some
      particular cases where the therapeutic choice tends towards the rehabilitation by
      epitheses. The improvement of texture and color of epitheses and the improvement
      of the possibilities of their osseous anchorage by implants (endo-osseous or
      juxta-osseous) permit to reconstruct that kind of complex facial wounds with
      restoration of oral function and with a good morphologic result.

PMID- 11599148
TI  - [Extra-oral implants and irradiation: current trends].
AB  - Recommended treatment for head and neck cancer associates surgery and
      radiotherapy. Indication for bone-anchored epitheses in irradiated patients is
      also a common situation. The outcome of the implant appears to be improved with a
      special protocol for hyperbaric oxygen therapy, antibiotic therapy and
      calcitherapy. The problem of radiotherapy in patients with titanium
      osseointegrated implants is also discussed.

PMID- 11599149
TI  - [Implant-supported prostheses: the value of surgeon-prosthetist collaboration].
AB  - For extra-oral implants, the difficulty is not simply the surgical technique,
      similar to that used for intra-oral implants. The real problem is to insert the
      implant at a specific position and with a proper alignment. The final cosmetic
      result is directly related to correct insertion of the implant and its anchors.
      We demonstrate the importance of a tight collaboration between the surgeon and
      the prosthesis, before, after and often during the intervention for obtaining a
      satisfactory result.

PMID- 11599150
TI  - [Bone-anchored hearing aids BAHA: 10 years' experience].
AB  - Bone anchored hearing aid (BAHA), based on the concept of osseointegration,
      offers the possibility of restoring hearing in case of conduction or mixed
      deafness. We report our experience with 87 in 74 patients implanted from 1989 to
      1999. The patients were divided into two major groups, with bilateral agenesia
      (22 cases) or chronic otitis media (52 cases). Anatomical results are very good.
      We got 3 extrusions with no osseointegration, 10% local infections and 3 traumas.
      Functional outcome was excellent, with 73 patients being fitted with 81 HC200,
      HC300 or HC360 prostheses. One patient had a functional failure. We stress the
      importance of rigorous audiometric criteria and the determinant factors of
      osseointegration, essentially the surgical technique. In patients with chronic
      otitis, BAHA offers a functional solution for those with no benefit from an air
      conduction hearing aid and who are not operable or decline a new operation for
      tympano-ossicular reconstruction. For cases of ear malformation, BAHA can be a
      temporary solution that does not damage the inner ear. Indeed, rehabilitation
      with a BAHA does not exclude the possibility of functional tympano-ossicular
      surgery when the child is older and if the anatomic conditions are favorable.

PMID- 11599151
TI  - [Permanent percutaneous connections and osteointegration].
AB  - Passage through the skin of an abutment anchored on an implant fixed on the
      underlying one constitutes a Permanent Percutaneous Connection of which the
      principal applications are stabilization of maxillofacial prosthesis (MFP) or
      bone anchored hearing aid (BAHA) support. The long-term outcome of a PPC depends
      on a variety of different parameters. We analyzed the influence of the most
      important factor: osseointegration.

PMID- 11599152
TI  - [From the concept of permanent percutaneous connections to that of permanent
      percutaneous electrical connections].
AB  - Percutaneous abutment of an extra-oral implant provides two main functions:
      support of bone anchored hearing aid (BAHA) and fixing maxillofacial prosthesis
      (MFP). Further developing this concept, and using available surgical strategies
      and materials, leads to a new application in extra-oral implantology. We analyzed
      the evolution of concepts in the field of permanent percutaneous connection (PPC)
      to the new concept of PPEC (permanent percutaneous electric connection),
      presenting a clinical case.

PMID- 11599153
TI  - [Present and future of biomedical research in Spain].

PMID- 11599154
TI  - [Differences in the quality of Spanish clinical trials published in international
      periodicals and of the ones presented in general medicine periodicals with wide
      readership].
AB  - BACKGROUND: The assessment of the methodological quality of controlled clinical
      trials (CCTs) carried out in Spain and published in international journals and
      the comparison with those published in widely read general journals of medicine
      (N Engl J Med, Lancet, JAMA, BMJ) may help establishing their limitations and
      improving quality in future studies. METHODS: Search in Medline of CCTs. Studies
      were evaluated according to a structured questionnaire (J Clin Epidemiol 1992;
      45:225-265). The odds ratio and their 95% confidence intervals were used to
      compare spanish studies with the remaining studies. The following variables were
      considered as confounders and controlled for by logistic regression analysis:
      number of participating centers, sample size, funding source, and the inclusion
      of epidemiologists in the research team. The journal's impact factor was taken
      into account. RESULTS: Spanish CTTs had a smaller sample size, were mostly
      monocentric, reported les frequently the source of funding, and exhibited a lower
      participation of epidemiologists. The informed consent and the approval by the
      ethics committee were more frequently omitted. The major methodological
      differences with the other studies were: lack of pre-study sample size and
      statistical power estimation, lack of inclusion criteria, poor explanation of
      patients' flow in the selection process, lack of explanation for unmasked
      procedures, poor description of methods to assess intervention compliance, under
      reporting confidence intervals, and less frequent use of the intention-to-treat
      principle. The quality score of spanish studies was lower (9.4 +/- 1.7 vs 10.7 +/
      1.5; p < 0.001). These limitations improved with higher journal's impact factor,
      the quality score was 8.5 in journals with an impact factor < 1.5, and 10.6 in
      those with an impact factor > 4.5. This last figure is almost identical to the
      average of CCTs published in general journals of medicine. CONCLUSIONS: Most
      spanish studies achieved a good quality score. Nevertheless, there are still
      issues which can be overcome easily. If this goal is achieved, the results will
      obtain a higher repercussion, as a better quality is observed in those published
      in journals with the highest impact factor.

PMID- 11599155
TI  - [Usefulness of induced sputum cytology in the study of central masses in elderly
      patients].
AB  - OBJECTIVE: To analyze the diagnostic yield of cytology obtained by means of
      sputum induction in elderly patients with central masses. METHODS: A total of 23
      patients older than 75 years with centrally located pulmonary masses identified
      by computerized tomography were studied. All patients collected three
      spontaneously produced sputum specimens and underwent three sputum-induction
      sessions. Induction was considered satisfactory when the patient expectorated
      within the following 15 minutes. All sputum specimens were processed by May
      Grunwald-Giemsa and Papanicolau staining techniques. The definite diagnostic was
      considered that obtained by means of bronchial biopsy or chest percutaneous
      aspirative puncture (PAP). RESULTS: With sputum induction, 19 patients (83%)
      collected satisfactory specimens and in 14 cases cytology was positive for
      malignancy (sensitivity 74%) and negative in five. No false-positive cases were
      recorded and in no patient did complications occur in association with sputum
      induction. The analysis of agreement between induced sputum and definite
      diagnosis showed a kappa index of 0.66. CONCLUSIONS: Among elderly patients with
      central pulmonary masses, the cytology of induced sputum should be considered as
      the first diagnostic procedure because of its harmlessness, remarkable
      sensitivity and high histologic correlation.

PMID- 11599156
TI  - [Conversion of fast insulin intensive therapy to lispro insulin in type I
      diabetes. Pharmacoeconomic analysis of cost-effectiveness].
AB  - In order to analyze the initial cost-effectiveness of transfer to two treatments
      with insulin lispro in type 1 diabetes, a pharmaco-economic study was conducted
      for nine months. After an educational reinforcement, a group of 30 C-peptide
      negative patients (31.8 +/- 11.5 years [mean +/- SD], time since diagnosis of
      diabetes of 9.2 +/- 7.1 years, and on intensive therapy for 5.3 +/- 3.1 years)
      initiated a 3-month basal period with their usual therapy (preprandial rapid
      insulin and nocturnal NPH). Patients were then randomly assigned to one of the
      two groups, changing rapid insulin to either lispro (L1) or lispro combined with
      15% to 20% NPH insulin (L2). Cross-over was made 3 months after the first
      treatment. Efficacy and safety were established by the assessment of HbA1c, self
      monitoring blood glucose and hypoglycemia rates. Therapy cost was measured by
      systematic examination of the injection devices and wastage of insulin. The mean
      prescribed and actually consumed doses for R, L1, L2 groups were 52.9, 57.1, 55.2
      U and 60.3, 64.1, 63 U per day, respectively (p < 0.001). The average of
      postprandial peak glucose (9.7, 8.4, 8.3 mM; p < 0.001) and HbA1c (7.6%, 7.2%,
      7.1%; p < 0.01) were significantly lower after L1 or L2 lispro therapy. Although
      no statistical differences in overall hypoglycemia rates were observed, fewer
      nocturnal episodes were detected (0.72, 0.37, 0.41 events/month). The mean daily
      cost for regular insulin treatment was lower (186.8, 241.8; 215.7 pts and 53.7
      pts per day. Efficacy and safety for two MIT regimens containing lispro were
      similar in the short run. Nevertheless, the preprandial use of the fast-acting
      insulin analog lispro in combination with a 15%-20% intermediate-acting NPH
      seemed to be more cost-effective than the premeal lispro therapy alone.

PMID- 11599157
TI  - [Paronychia in patients infected with HIV treated with indinavir].
AB  - A retrospective study of cases of paronychia associated with anti-retroviral
      therapy diagnosed in two general hospitals is here reported. Lesions appeared
      from 3 and 48 months after institution of therapy. At diagnosis, 84.6% of
      patients were on indinavir therapy. CD4 values ranged from 120 and 1,332
      cells/mm3 and viral load was lower than 200 copies/ml in 92.3 of cases.
      Conservative therapy was applied in 7 patients and surgery in 6. In all patients
      indinavir therapy was discontinued, and cure was achieved 16 weeks later. The
      "retinoid" effect of indinavir is discussed as likely pathogenic explanation for
      this complications. We advocate for topic therapy and change of anti-retroviral
      therapy, reserving surgery for patients not responding to therapy. Pain and
      functional limitation caused by this non uncommon complication (1.6% of our
      patients treated with anti-retroviral agents) makes its knowledge necessary and
      an active search by clinicians in patients receiving indinavir therapy.

PMID- 11599158
TI  - [Indications for small intestine biopsy].

PMID- 11599159
TI  - [Reality of myth of osteoporosis prevention in postmenopausal women].

PMID- 11599160
TI  - [Current status of calcitonin use in osteopenia/osteoporosis].

PMID- 11599162
TI  - [Clinical relevance and diagnosis of gastroesophageal reflux].

PMID- 11599161
TI  - [Management of dilated cardiomyopathy].

PMID- 11599163
TI  - [Vitamins in geriatric nutrition].

PMID- 11599165
TI  - [Patient with nodular splenomegaly. Littoral cell angioma of the main and
      accessory spleen].

PMID- 11599164
TI  - [Acute meningitis in patients with craniocerebral trauma. Acute meningitis caused
      by csf fistula after traumatic basilar fracture].

PMID- 11599166
TI  - [Constrictive pericarditis and monolobular hepatic cysts. Monolobular Caroli
      disease].

PMID- 11599167
TI  - [Lumbar pain and prolonged fever. Psoas abscess secondary to lumbar
      spondylodiscitis].

PMID- 11599168
TI  - [Headache and tongue deviation].

PMID- 11599169
TI  - [Listeria monocytogenes aortitis].

PMID- 11599170
TI  - [Inflammatory pseudotumor: report of 12 cases].

PMID- 11599171
TI  - [Acute generalized exanthematous pustulosis. Report of 2 cases].

PMID- 11599172
TI  - [Allopurinol hypersensitivity syndrome].

PMID- 11599173
TI  - [Splenic non-Hodgkin's lymphoma. Report of a new case and review of the
      literature].

PMID- 11599174
TI  - Redox history of the Earth's interior since approximately 3900 Ma: implications
      for prebiotic molecules.
AB  - The history of the oxidation state in the Earth's mantle has been constrained
      using (a) the whole-rock abundances of Cr and V in ancient volcanics, and (b) the
      composition of Cr-rich spinels in ancient volcanics. Results indicate that the
      Earth's mantle has been at-or-near its current oxidation state (+/- 0.5 log-unit
      fO2) since at least 3600 Ma, and probably since at least 3960 Ma. Volatiles
      released into the Earth's atmosphere by high-temperature (T > or = 1300 K)
      volcanism during this time have been dominated by H2O, CO2, and SO2. This blend
      of volatiles is known to provide smaller yields of prebiotic, organic molecules
      by atmospheric and surface processes than gas mixtures containing higher
      concentrations of reduced species such as H2, CO, and H2S (e.g., Miller, 1998;
      Zolotov and Shock, 2000). The results discussed in this article independently
      support the conclusion of Canil (1997, 1999). If the atmosphere was reducing
      (e.g., CH4, H2, H2S, NH3, CO) at any time during the last approximately 3900 Ma,
      high-temperature volcanic outgassing was not the cause of it.

PMID- 11599175
TI  - Modulation of adenosine 5'-monophosphate adsorption onto aqueous resident pyrite:
      potential mechanisms for prebiotic reactions.
AB  - The adsorption of adenosine 5'-monophosphate (5'-AMP) onto pyrite (FeS2) and its
      modulation by acetate, an organic precursor of complex metabolic pathways, was
      studied in aqueous media that simulate primitive environments. 5'-AMP adsorption
      requires divalent cations, indicating that a cationic bridge mediates its
      attachment to negatively charged sites of the mineral surface. The isotherm of 5'
      AMP adsorption exhibits a strong cooperative effect at low nucleotide
      concentrations in acetate-rich medium, whereas high levels of adsorption were
      only found at high nucleotide concentrations in a model of primitive seawater
      (acetate free). The modulating role of acetate is also evidenced in the presence
      of high dipolar moment molecules: dimethyl sulfoxide (Me2SO) and dimethyl
      formamide (DMF) strongly inhibit 5'-AMP adsorption in acetate-rich media, whereas
      no effect of DMF was found in artificial seawater. The observation that exogenous
      divalent cations are not needed for acetate attachment onto FeS2 reveals that
      organic acids can interact with the Fe2+ atoms in the mineral surface. All
      considered, the results show that complex and flexible ironsulfide/biomonomers
      interactions can be modulated by molecules that accumulate in the interface
      layer.

PMID- 11599176
TI  - The rates of hydrolysis of thymidyl-3',5'-thymidine-H-phosphonate: the possible
      role of nucleic acids linked by diesters of phosphorous acid in the origins of
      life.
AB  - Thymidyl-3',5'-thymidine H-phosphonate undergoes acid, base, and water-catalyzed
      hydrolysis. The products were 3'-thymidine H-phosphonate, 5'-thymidine H
      phosphonate, and thymidine in a ratio of 1:1:2. The rate constants are 1.8 x 10(
      3) M-1 sec-1, 7.2 x 10(3) M-1 sec-1, and 1.5 x 10(6) sec-1 for acid, base and
      water catalysis, respectively. These values are comparable with previous reports
      for the rates of hydrolysis of simple dialkyl esters of phosphorous acids. The
      Arrhenius activation energy for the base-catalyzed reaction is 20 kcal/mol. and
      the enthalpy and entropy of activation are 19 kcal/mol and -14 eu., respectively.
      The Gibbs free energy of activation is 23 kcal/mol. The rate constants suggest
      that nucleic acids linked by diesters of phosphorous acid hydrolyze too rapidly
      in aqueous solution to have accumulated in useful amounts on the primitive Earth.

PMID- 11599177
TI  - Effect of inhibitors on the montmorillonite clay-catalyzed formation of RNA:
      studies on the reaction pathway.
AB  - The Langmuir adsorption isotherms of the phosphoroimidazolides of adenosine
      (ImpA) and uridine (ImpU), dA5' ppdA and N6,N6-dimethyladenine binding on
      montmorillonite are consistent with their forming a monolayer on the clay
      surface. This suggests the condensation of ImpA and ImpU to oligomers proceeds on
      the surface of the clay and not in groups of monomers stacked on the clay
      surfaces. The binding and reactions of ImpU and ImpA on montmorillonite are
      blocked by N6,N6-dimethyladenine and dA5' ppdA. dA5' ppdA is a better inhibitor
      of oligomer formation than N6,N6-dimethyladenine because both adenine rings of
      dA5' ppdA bind to the clay surface and block adjacent catalytic sites. An upper
      limit of 5-10 x 10(15) catalytic sites on 50 mg of clay was estimated from the
      binding of ImpU and the inhibition of oligomer formation by dA5' ppdA.

PMID- 11599179
TI  - Contributions of icy planetesimals to the Earth's early atmosphere.
AB  - Laboratory experiments on the trapping of gases by ice forming at low
      temperatures implicate comets as major carriers of the heavy noble gases to the
      inner planets. These icy planetesimals may also have brought the nitrogen
      compounds that ultimately produced atmospheric N2. However, if the sample of
      three comets analyzed so far is typical, the Earth's oceans cannot have been
      produced by comets alone, they require an additional source of water with low
      D/H. The highly fractionated neon in the Earth's atmosphere may also indicate the
      importance of non-icy carriers of volatiles. The most important additional
      carrier is probably the rocky material comprising the bulk of the mass of these
      planets. Venus may require a contribution from icy planetesimals formed at the
      low temperatures characteristic of the Kuiper Belt.

PMID- 11599178
TI  - The evolution of acetyl-CoA synthase.
AB  - Acetyl-coenzyme A synthases (ACS) are Ni-Fe-S containing enzymes found in archaea
      and bacteria. They are divisible into 4 classes. Class I ACS's catalyze the
      synthesis of acetyl-CoA from CO2 + 2e-, CoA, and a methyl group, and contain 5
      types of subunits (alpha, beta, gamma, delta, and epsilon). Class II enzymes
      catalyze essentially the reverse reaction and have similar subunit composition.
      Class III ACS's catalyze the same reaction as Class I enzymes, but use pyruvate
      as a source of CO2 and 2e-, and are composed of 2 autonomous proteins, an alpha 2
      beta 2 tetramer and a gamma delta heterodimer. Class IV enzymes catabolize CO to
      CO2 and are alpha-subunit monomers. Phylogenetic analyses were performed on all
      five subunits. ACS alpha sequences divided into 2 major groups, including Class
      I/II sequences and Class III/IV-like sequences. Conserved residues that may
      function as ligands to the B- and C-clusters were identified. Other residues
      exclusively conserved in Class I/II sequences may be ligands to additional metal
      centers in Class I and II enzymes. ACS beta sequences also separated into two
      groups, but they were less divergent than the alpha's, and the separation was not
      as distinct. Class III-like beta sequences contained approximately 300 residues
      at their N-termini absent in Class I/II sequences. Conserved residues identified
      in beta sequences may function as ligands to active site residues used for acetyl
      CoA synthesis. ACS gamma-sequences separated into 3 groups (Classes I, II, and
      III), while delta-sequences separated into 2 groups (Class I/II and III). These
      groups are less divergent than those of alpha sequences. ACS epsilon-sequence
      topology showed greater divergence and less consistency vis-a-vis the other
      subunits, possibly reflecting reduced evolutionary constraints due to the absence
      of metal centers. The alpha subunit phylogeny may best reflect the functional
      diversity of ACS enzymes. Scenarios of how ACS and ACS-containing organisms may
      have evolved are discussed.

PMID- 11599181
TI  - [Fibromyalgia: the pros for a cease-fire between supporters of the psychosomatic
      social and those of the all biochemical aspects].

PMID- 11599180
TI  - Exo/Astrobiology in Europe.
AB  - The question of the chemical origins of life is engraved in the European
      scientific patrimony as it can be traced back to the pioneer ideas of Charles
      Darwin, Louis Pasteur, and more recently to Alexander Oparin. During the last
      decades, the European community of origin of life scientists has organized seven
      out of the twelve International Conferences on the Origins of Life held since
      1957. This community contributed also to enlarge the field of research to the
      study of life in extreme environments and to the search for extraterrestrial
      life, i.e. exobiology in its classical definition or astrobiology if one uses a
      more NASA-inspired terminology. The present paper aims to describe the European
      science background in exo/astrobiology as well as the project of a European
      Network of Exo/Astrobiology.

PMID- 11599182
TI  - [Fibromyalgia: non-entity or double agent?].

PMID- 11599183
TI  - [Update in pneumology].
AB  - The end of the century has not brought any great modification in pneumology
      therapy. Prospective studies in asthma using combined therapeutic approaches,
      systemic or local steroid treatment in mild or moderate chronic obstructive
      pulmonary disease or itraconazole in allergic bronchopulmonary aspergillosis are
      summarized in this review. Innovation is coming from radiology, with confirmation
      of the interest of positive-emission tomography for the preoperative stage of
      lung cancer.

PMID- 11599185
TI  - [Stroke management in a general internal medicine department: results of a survey
      regarding practice].
AB  - PURPOSE: The incidence of strokes in the general population and the insufficient
      numbers of centers specialized in their management has led to the increased
      hospitalization of patients in general, internal medicine departments. The
      prognosis for patients is related to the relevance of the initial diagnostic and
      therapeutic measures. To optimize management of stroke patients outside of
      specialized units, a survey concerning practice was conducted in internal
      medicine departments in western France, and a meeting was held to define
      guidelines. METHODS: Data sheets were mailed to practitioners in internal
      medicine departments prior to the survey. The following data were recorded for
      each patient hospitalized during the two-week study: age, sex, clinical
      characteristics of stroke, risk factors, investigations performed, and initial
      and subsequent medical management. On the basis of the results, management
      guidelines were considered and defined. RESULTS: Patients hospitalized for a
      stroke in internal medicine departments have a similar profile to those
      hospitalized in neurology departments. CT-scan and EKG recordings were performed
      in most patients whereas other investigations (cervical ultrasound,
      echocardiography, MRI) were used less frequently. The use of rehabilitation and
      therapeutic strategies for secondary stroke prevention were not always performed
      according to current guidelines. CONCLUSION: Internal medicine departments are
      frequently involved in the care of stroke patients. The present study of clinical
      practice may help to improve stroke management in these non-specialized
      departments.

PMID- 11599184
TI  - [Pulmonary hypertension screening in systemic scleroderma: a cohort study of 67
      patients].
AB  - PURPOSE: Pulmonary hypertension is a severe complication of systemic sclerosis
      and has emerged as a major cause of morbidity and mortality in this condition.
      Treatment is all the more efficient as pulmonary hypertension is early diagnosed.
      A good knowledge of the clinical, biological and functional features of pulmonary
      hypertension in systemic sclerosis is therefore necessary to suspect and to
      diagnose pulmonary hypertension as early as possible. METHODS: Sixty seven
      patients with systemic sclerosis were retrospectively studied. We compared
      clinical, immunological, functional (spirometry) and morphological (pulmonary
      fibrosis) features according to the presence (n = 25) and the characteristic of
      pulmonary hypertension (isolated or secondary) or the absence (n = 42) of
      pulmonary hypertension, assessed by Doppler echocardiography. RESULTS: CREST
      syndrome (calcinosis, Raynaud's phenomenon, oesophageal involvement,
      sclerodactyly and telangiectasia) was more frequent in patients with isolated
      pulmonary hypertension than in patients without PH (72.7% vs 28.5%, P < 0.05;
      odds-ratio [OR] = 6.6) and dyspnea was more severe (P < 0.001; OR = 11.4). The
      age at time of pulmonary hypertension diagnosis was higher in patients with
      secondary pulmonary hypertension than in patients with isolated from (median:
      62.5 years (range: 32-35) vs 53 years (range: 37-85), P < 0.05). Patients with
      isolated pulmonary hypertension had anticardiolipin antibodies more frequently
      than patients without pulmonary hypertension (72.7% vs 35.7%, P < 0.05). Isolated
      reduction of diffusing capacity was preferentially observed among patients with
      isolated pulmonary hypertension than among those without pulmonary hypertension.
      A linear relation between systolic pulmonary artery pressure values and diffusing
      capacity values (r = 0.72, P < 0.01) was found. Isolated reduction of diffusing
      capacity was more frequent in patients with isolated pulmonary hypertension than
      in patients without pulmonary hypertension (63.6% vs 14.3%, P < 0.001; OR =
      10.5). CONCLUSION: The severity of pulmonary hypertension in systemic sclerosis
      justifies a systematic screening by Doppler echocardiography and diffusing
      capacity measurement. Our results allow us to better define the characteristics
      of sclerodermic patients with isolated or secondary pulmonary hypertension. The
      search for pulmonary hypertension should be repeated with time and clinicians
      should be particularly vigilant in the case of a patient presenting these
      characteristics.

PMID- 11599186
TI  - [Skin manifestations associated with myelodysplastic syndromes].
AB  - PURPOSE: Our purpose was to describe cutaneous manifestations associated with
      myelodysplastic syndromes. METHODS: Data from seven patients with cutaneous
      vasculitis (four cases), neutrophilic dermatosis (one case), relapsing
      polychondritis (one case), and possible erythema elevatum diutinum (one case) in
      association with myelodysplastic syndrome (refractory anaemia RA, RA with excess
      of blasts--RAEB-, RAEB in transformation RAEBt, chronic myelomonocytic leukaemia-
      CMML-), and analysis of the literature were reviewed. RESULTS: The cutaneous
      manifestations of myelodysplastic syndrome may or may not be specific, and may
      reveal hemopathy transformation. The cutaneous vasculitis are the most frequent
      and polymorphic. The relation with neutrophilic dermatosis is more specific; they
      are a spectrum of diseases including pyoderma gangrenosum, Sweet's syndrome,
      erythema elevatum diutinum (nuclear segmentation anomalies of neutrophils both in
      the skin and in the blood are a biological marker of the association). Relapsing
      polychondritis is significantly associated with myelodysplastic syndromes. Their
      pathogenesis are controversial. CONCLUSION: Early biopsy of cutaneous lesions in
      myelodysplastic syndromes is indicated. Analysis of blood cell count (and more
      bone marrow biopsy in relapsing polychondritis) is indispensable in these
      neutrophilic cutaneous or vasculitis diseases.

PMID- 11599188
TI  - [Bacterial cerebral aneurysms without infectious endocarditis: analysis of a case
      and review of the literature].
AB  - INTRODUCTION: Bacterial intracerebral aneurysms, which are a common complication
      of infectious endocarditis, are unusual without Osler's disease. EXEGESIS: From
      the case report of a man with a bilateral bacterial intracranial aneurysm without
      endocarditis resulting in an hypopituitarism, we undertook a literature review of
      bacterial intracerebral aneurysms without endocarditis. CONCLUSION: Although this
      review has found few cases, this kind of aneurysms seems to have different
      features from those secondary to infective endocarditis: younger age of
      incidence, majority of Staphylococcus aureus, clinical presentation as a
      thrombophlebitis of the cavernous sinus, location of aneurysm on bigger cerebral
      artery.

PMID- 11599187
TI  - [Acquired hemophilia: current diagnostic and therapeutic approaches].
AB  - PURPOSE: Acquired haemophilia is a rare disease, occurring most frequently in
      elderly patients, caused by the development of autoantibodies against factor
      VIII. CURRENT KNOWLEDGE AND KEY POINTS: The disease is characterised by
      spontaneous haemorrhagic complications which can be fatal in 15-20% of the
      patients. However spontaneous remission is possible and in fact natural evolution
      and aetiology are still partly unknown. Acquired haemophilia may arise in
      association with auto-immune diseases, lymphoproliferative malignancy, pregnancy
      and also as a drug reaction. The aims of the treatment are first to treat the
      bleeding which is the most common cause of morbidity and mortality, and second to
      eliminate the inhibitor by immunosuppression. However no consensus exists for
      these two parts of the treatment. Bleeding may be controlled by prothrombin
      complex concentrates, recombinant factor VIIa or porcine factor VIII. The
      inhibitor is abolished in up 70% of patients using prednisone and
      cyclophosphamide. Other combinations of prednisone with azathioprine or with
      cyclophosphamide and vincristine or the use of high-dose immunoglobulin or double
      filtration plasmapheresis have also proven effective in some patients. FUTURE AND
      PROJECTS: The rare occurrence of the disease, the associated with various
      diseases, and lack of consensus about treatment, require multicentric prospective
      studies.

PMID- 11599189
TI  - [Laparoscopic diagnosis of stenosing eosinophilic jejuno-ileitis].
AB  - INTRODUCTION: Eosinophilic gastroenteritis of unknown origin could be isolated or
      integrated in idiopathic hypereosinophilic syndrome. Clinical expression is
      variable since the lesion may affect any area of the gastrointestinal tract and
      any layer of the wall. EXEGESIS: A 25-year-old male patient had digestive
      symptoms such as peritoneal, obstructive and diarrheal signs, associated with
      blood eosinophilia, giving evidence for eosinophilic jejuno-ileitis. Computer
      tomography revealed an extensive obstruction of the jejuno-ileum and thickening
      of the intestinal wall. The diagnosis was obtained using laparoscopy and
      controlled wedge biopsy, which showed a predominantly external infiltration of
      the intestinal wall by eosinophils. The disease evolution was favorable with
      corticosteroid therapy. CONCLUSION: Worrying and persistent digestive
      symptomatology, associated with blood eosinophilia, particularly when intestinal
      wall infiltration is revealed by computer tomography, should lead one to perform
      a laparoscopy to guide a surgical biopsy of the intestinal wall.

PMID- 11599190
TI  - [Ecthyma gangrenosum caused by Pseudomonas aeruginosa without septicemia in a
      neutropenic patient].
AB  - INTRODUCTION: Ecthyma gangrenosum is a rare skin infection caused by gram
      negative bacteria. It involves immunocompromised patients, especially neutropenic
      patients, and can be easily diagnosed. EXEGESIS: We report a case of ecthyma
      gangrenosum without septicemia due to Pseudomonas aeruginosa in a myelodysplastic
      patient with severe neutropenia. Granulocyte growth factors adjunction was
      necessary in combination to antibiotics to obtain complete healing. CONCLUSION:
      In neutropenic patient, ecthyma gangrenosum due to Pseudomonas aeruginosa should
      be rapidly diagnosed to avoid septicemic complications. In the case of antibiotic
      treatment failure, granulocyte growth factors may be added. Frequent Pseudomonas
      aeruginosa infections justify bacteriologic survey to look for hospital
      contamination.

PMID- 11599191
TI  - [Uterine sarcoma in patients receiving tamoxifen therapy. Apropos of 2 cases].
AB  - INTRODUCTION: Tamoxifen--a non steroidal triphenylethyl compound--in addition to
      having antiestrogenic properties may provoke weak estrogenic effects, the well
      known "paradoxical effects" on the female genital tractus. Concern has been
      raised about prolonged tamoxifen treatment and subsequent occurrence of
      endometrial adenocarcinoma; subsequent attention has been drawn through high risk
      histologic subtypes including poorly differentiated patterns and uterine
      sarcomas. EXEGESIS: We report two cases of uterine sarcoma arising in
      postmenopausal women taking tamoxifen, 20 mg daily during 38 and 42 months, for
      breast carcinoma: one leiomyosarcoma and one endometrial stromal sarcoma; both
      cases were asymptomatic and detected by pelvic sonography. CONCLUSION: Further
      studies will be required to establish if there is a relationship between long
      term tamoxifen exposure and highly aggressive types of cancer of the uterine
      corpus exhibiting adverse histologic features such as uterine sarcomas. There is
      no consensus regarding uterine surveillance of women receiving tamoxifen. We
      advocate an annual gynecologic examination plus imaging by means of transvaginal
      ultrasonography.

PMID- 11599192
TI  - [A less threatening vertebral lytic lesion].

PMID- 11599193
TI  - [Pulmonary epithelioid hemangioendothelioma: a tumor with an atypical course not
      to be unrecognized].

PMID- 11599194
TI  - [Atrophic polychondritis and Hashimoto's thyroiditis: apropos of a case].

PMID- 11599195
TI  - [Atrophic polychondritis associated with rectal adenocarcinoma and muscular
      aponeurotic fibromatosis in an African woman].

PMID- 11599196
TI  - [Chronic myeloid leukemia and tyrosine kinase inhibitors].
AB  - INTRODUCTION: Chronic myeloid leukemia is a myeloproliferative disorder
      clinically characterised by a triphasic course: after a chronic phase over a
      median time of 4 years, patients developed an accelerated phase, then a blastic
      phase, resulting in the patient's death with 3 to 6 months. PURPOSE: During the
      last past years, progress have been made in the understanding of the molecular
      mechanism responsible of leukemic growth. This has also provided support for a
      therapeutic improvement with the appearance of treatment such as tyrosine kinase
      inhibitors which specifically target the oncoprotein inside the leukemic cells.
      CONCLUSION: These treatments, such as STI571 or Glivec, are at present in
      clinical trials, and could be the medicines for the future. Thus, chronic myeloid
      leukemia is also a model for the development of the new therapeutic drugs.

PMID- 11599197
TI  - Pharmaceutical care until the end: the role of pharmacists in euthanasia in The
      Netherlands.
AB  - Euthanasia and physician-assisted suicide continue to remain a controversial
      point of discussion in today's society. Patients will seek to increase their role
      in the decisions concerning their own health and death care. Pharmacists are also
      confronted with euthanasia: they not only have to provide the necessary drugs,
      but are also affected in every area of their life. Euthanasia can be seen as a
      contradiction to the mission of pharmacy practice. If, however, the activities of
      pharmacists include pharmaceutical care, the contradiction may not necessarily be
      present. Pharmaceutical care begins with the recognition that responsibilities of
      patient care cannot be relegated solely to other health professionals.
      Pharmaceutical care recognizes some of the most important needs of the terminally
      ill. If based on a patient-centered approach, euthanasia might be a logical last
      step in the efforts to alleviate the patient's sufferings.

PMID- 11599198
TI  - Long-term therapy with spironolactone.
AB  - OBJECTIVE: To evaluate the duration of therapy with spironolactone in daily
      practice. METHOD: A retrospective follow-up of a cohort of patients with a first
      prescription for spironolactone between January 1, 1990 and December 31, 1996 and
      at least one hospital discharge for CHF in the preceding year. RESULTS: 243
      patients met the inclusion criteria and were followed until the end of data
      collection. The average starting dosage of spironolactone was 55 mg. 143 patients
      (58.8%) discontinued spironolactone therapy before the end of follow-up. 98
      patients (40.8%) discontinued within 6 months of follow-up. Of the 137 patients
      (56.4%) who did use spironolactone and an ACE-inhibitor concomitantly, only 45
      (32.8%) continued this combination until the end of follow-up. The remainder of
      the patients discontinued either the ACE-inhibitor (10.9%) or spironolactone
      (12.4%) or both (43.8%). CONCLUSION: While the reasons for discontinuation remain
      unclear, our data suggest that it is difficult to keep patients on both drugs. It
      is not certain whether these findings from past spironolactone use can be
      extrapolated to future use. Patients in the general population received higher
      average spironolactone dosages compared to the RALES study (55 mg vs. 26 mg),
      possibly resulting in more adverse effects and partly explaining the high
      discontinuation rate.

PMID- 11599199
TI  - The introduction of pharmacoeconomic analysis in Norway--are the users prepared?
AB  - OBJECTIVE: The aim of this study was to investigate existing perceptions and
      knowledge of pharmacoeconomic analyses, and attitudes towards them, among
      personnel from the pharmaceutical authorities and the pharmaceutical industry in
      Norway who work with medicines in various capacities, and to investigate whether
      there were evident differences between the two groups. METHODS: Personal
      interviews were conducted with 33 employees from the public authorities and 46
      from the pharmaceutical industry, using a semi-structured questionnaire. This
      focused on knowledge of and attitudes towards pharmacoeconomics. MAIN OUTCOME
      MEASURE: A factor analysis conducted on questions related to attitude. RESULTS:
      The factor analysis showed that the employees from the public authorities were
      significantly more positive to the introduction and use of pharmacoeconomic
      analyses than those from the industry, and they were less skeptical about how
      well prepared or receptive the market is. In addition the informants from both
      groups had a relatively good understanding of the terms most commonly used in the
      field of pharmacoeconomics. They were also aware of some of the costs and
      outcomes involved in the analyses. CONCLUSION: If the groups interviewed are to
      become more involved in actual decision-making on the basis of pharmacoeconomic
      analyses, they need more training to gain the necessary in-depth knowledge, since
      their knowledge of the field was somewhat superficial.

PMID- 11599200
TI  - Number of non-diabetic drugs: a simple comorbidity indicator for diabetes?
AB  - INTRODUCTION: The number of non-diabetic drugs, taken by a patient with diabetes
      at any one point in time, has been validated in previous studies as a comorbidity
      indicator. AIM: The aim of the paper is to examine the relationship between this
      comorbidity indicator and health status in people with Type 2 diabetes. METHOD:
      The analysis presented is from a prospective cohort study of people with Type 2
      diabetes before and after commencing insulin therapy, with simultaneous
      collection of health status, clinical and other comparative data. RESULTS: Of the
      48 people for whom both health status and drug data were available, 26 (54%) were
      taking at least one non-diabetic drug and 16 (33%) were taking 3 or more non
      diabetic drugs, at the baseline assessment. There were no significant
      relationships between the number of non-diabetic drugs taken, and age, duration
      of diabetes or baseline HbA1c measurements. However, there were statistically
      significant relationships between the number of non-diabetic drugs and health
      status, in terms of depression and physical function. CONCLUSION: Drug data are
      routinely recorded in primary care and therefore the number of non-diabetic drugs
      is a potentially widely available indicator. This indicator could be a useful,
      simple addition to datasets that not only proxies comorbidity but also relates to
      patients' physical function and depression status.

PMID- 11599201
TI  - Evaluation of antiparkinsonian drugs in pharmacy records as a marker for
      Parkinson's disease.
AB  - AIM: The aim of this study was to determine whether use of antiparkinsonian drugs
      in pharmacy records can be used as a marker for patients with Parkinson's disease
      (PD). METHOD: Data were obtained from the Rotterdam Study, a community-based
      prospective cohort study among people aged 55 years or older who were all
      screened for PD. For 5510 persons, of whom 74 had PD, pharmacy records were
      available. Stepwise logistic regression analysis was used to evaluate whether
      age, sex and use of the antiparkinsonian drugs amantadine, anticholinergics,
      dopamine agonists, levodopa and selegiline, were predictive variables for PD. For
      each individual a probability for having PD was calculated. Sensitivity,
      specificity and positive predictive value (PPV) were calculated at different cut
      off values based on calculated probabilities. RESULTS: More than 90% of the users
      of levodopa, bromocriptine, selegiline, and users of at least two different
      antiparkinsonian drugs had PD. Age, use of amantadine, anticholinergics,
      bromocriptine, levodopa, and selegiline were predictive variables for PD. After
      application of different cut-off values, sensitivity was at most 66.2%, and
      specificity was at least 99.8%. A PPV of higher than 90% was obtained at higher
      probabilities. CONCLUSION: Based on the high PPV of our predictive model,
      antiparkinsonian drugs can be used as a reliable marker for PD in pharmacy
      records. Because sensitivity is low, pharmacy records cannot be used to estimate
      prevalence of PD.

PMID- 11599202
TI  - Polypharmacy among patients admitted to hospital with rheumatic diseases.
AB  - AIM: This study describes polypharmacy among patients admitted to hospital with
      rheumatic diseases. METHODS: The study was performed in departments of
      rheumatology at nine Norwegian hospitals during five weeks in 1998. Pharmacists
      recorded all drugs on admittance among patients 18 years or older with rheumatic
      diseases. RESULTS: Sixty percent of 313 patients had polypharmacy defined as the
      concurrent use of five or more drugs, and this was most frequent among the older
      patients. However, they used fewer antirheumatic drugs compared to the younger
      patients. With regard to the three most common drug groups, older patients used
      more corticosteroids, and less nonsteroidal antiinflammatory drugs (NSAIDs) and
      disease modifying antirheumatic drugs (DMARDs), compared to the younger. Eighty
      four percent of patients on methotrexate used folic acid, but only 52% of the
      patients who used corticosteroids used calcium supplements. CONCLUSION:
      Polypharmacy among patients with rheumatic diseases is common, and the present
      description could be useful for drug-related interventions.

PMID- 11599203
TI  - The role of the Danish community pharmacist: perceptions and future scenarios.
AB  - In recent decades, dramatic changes of the role of the Danish community
      pharmacist have contributed to widespread uncertainty among professionals about
      the future content of their job. This case study, which is based on qualitative
      research interviews and documentary material, describes how key actors belonging
      to 10 different relevant social groups who have been influential in shaping the
      role of Danish community pharmacists have different perceptions of the pharmacy
      profession. These perceptions include: the community pharmacist as a provider of
      technical, standardised advice, the pharmacist as a drug expert, the pharmacist
      as a leader, and the pharmacist as a provider of individualized advice. Five
      future scenarios for the community pharmacist ranging from a role as a pharmacist
      with no future to a role as the provider of individualized information and future
      role developer are also described and analysed in the paper. The case study is
      theoretically based on a specific social constructivist theory, the Social
      Construction of Technology (SCOT).

PMID- 11599204
TI  - Epidemiology of amputations and severe injuries of the hand.
AB  - In a prospective population-based study, all open hand, wrist, and forearm
      injuries that were treated during a 10-year period, at hospitals and emergency
      wards in three Norwegian cities with 225,000 inhabitants, were registered. Injury
      severity was graded using the abbreviated injury scale (AIS). For moderate
      injuries (AIS 2) overall incidence (95% CI) was 59 (56-62), incidence among males
      92 (86-98), and among females 28 (25-31) per 100,000 person-years. For severe
      injuries (AIS > or = 3), overall incidence (95% CI) was 7.5 (6.3-8.6), incidence
      among males 11.1 (9.1-13.1), and among females 4.0 (2.8-5.2) per 100,000 person
      years. In a second study, all upper extremity amputation and devascularization
      injuries were referred during a 9-year period to the only replantation center in
      a southern Swedish region where 1.6 million inhabitants were analyzed. The
      incidence rate (95% CI) for upper extremity amputation or devascularization
      injuries potentially requiring replantation or revascularization was 1.9 (1.7
      2.1), incidence among males 3.3 (2.9-3.7), and among females 0.5 (0.4-0.7) per
      100,000 person-years.

PMID- 11599205
TI  - Patient participation in the decision for replantation.
AB  - It is widely accepted that medical decision making should consider the wishes of
      the patient. In contrast, traditional decision making in replantation has been
      based primarily on the expected functional outcome of the replantation as
      represented in the literature. Conflicts can occur when the patient seeks to
      exercise a positive right to replantation against the wishes of the surgeon. The
      field of decision science has developed a framework to study and consider this
      problem so that it can be applied to replantation. The concept of evidence
      informed patient choice is applicable to replantation, but is tempered by several
      problems, including the need for decision making in an emergency situation.

PMID- 11599206
TI  - Intervention approaches against I/R-induced arterial insufficiency in
      reconstructive surgery.
AB  - Ischemia and reperfusion in skeletal muscle is unavoidable during many
      reconstructive surgeries. Typical examples include replantation, transplantation,
      and free muscle transfer. One important complication during or after surgery is
      arterial insufficiency or a no-reflow phenomenon. The microcirculation is a
      primary target of ischemia and reperfusion injury. Vasoconstriction, poor blood
      flow, and capillary no-reflow, are the prominent features in the microcirculation
      seen during reperfusion. Currently, extensive efforts have focused on the theory
      that reactive oxygen species induce endothelial dysfunction in the
      microcirculation during reperfusion. Some intervention approaches, including
      ischemic preconditioning, are developing to interfere with or modulate the
      pathophysiological processes that are set in motion during ischemia and
      reperfusion.

PMID- 11599207
TI  - The treatment of major devascularizing injuries of the upper extremity.
AB  - The most complex aspect of managing major devascularizing injuries is decision
      making. The decision to amputate or revascularize is not difficult in injuries
      that have extremely favorable or unfavorable outcomes. In less obvious cases,
      however, decision making can be extremely complex, and many factors influence the
      surgeon's decision. In borderline cases, the optimal decision may never become
      clear, even in hindsight, much less at the time of the initial surgery. Nor are
      the ramifications of these decisions trivial. The decision whether to attempt
      revascularization or perform a revision amputation can have a profound influence
      on the course of a patient's life. Despite the critical nature of these
      decisions, there are few firm data to guide the decision-making process in
      complex cases. In addition, there are a virtually infinite number of possible
      injury presentations, and each factor to be considered has shades and gradations
      of its own. Ultimately, the decision comes down to the surgeon's knowledge,
      experience, and ability to project the expected risk-benefit ratios of the
      various options and, at the same time, attempt to account for all the factors
      that may influence outcome. Where more than one reasonable option exists, the
      patient's or family's wishes can be a critical factor as well.

PMID- 11599208
TI  - Major upper limb replantation.
AB  - Major amputations remain a challenge to the replantation surgeon. Proper patient
      selection, good surgical skills, and cooperation among the patient, surgeon, and
      rehabilitation team help achieve a better outcome.

PMID- 11599209
TI  - Revascularization of the digits and palm.
AB  - In 1962, Kleinert and Kasden performed the first successful revascularization of
      an incompletely amputated thumb. This was followed, in 1965, by Komatsu and
      Tamai, who performed the first successful replantation of a thumb. Since then,
      microsurgery has helped to solve a wide variety of difficult surgical problems
      and achieve a more functional and cosmetically acceptable digit. These problems
      include ring avulsions, distal finger amputations, and degloved skin.

PMID- 11599210
TI  - Digital replantations including fingertip and ring avulsion.
AB  - To reduce ischemic time and yet achieve a high-quality repair, the replantation
      team should be well organized. The team should be conversant with microvascular
      techniques and employ efficient methods of tendon repair and bone fixation.
      Developments in instrumentation and technique in recent years have improved
      success rates and consequently enlarged the indications for replantation surgery.
      Nevertheless, the economics of care and long-term functional outcome should not
      be overlooked, and these issues remain unresolved in the replantation versus
      terminalization question. The authors address topics relevant to replantation,
      including techniques and complications of digital replantation, ring avulsion
      injuries, and distal replantation.

PMID- 11599211
TI  - Replantation of the thumb, especially avulsion.
AB  - In replantation for avulsion amputation of the thumb, high survival rate of
      replanted digits depends on good debridement, good arterial repair with vein
      grafts or neurovascular bundles, and good coverage, with loose closure of the
      wound. The functional success depends on liberal use of nerve and tendon grafts
      or transfer; subsequent procedures, such as tenolysis and opponensplasty; and
      backup procedures for cases with severe soft tissue avulsion or long ischemic
      periods. All thumb amputations should be explored in the operating room for
      evaluation of replantability. If it is still questionable, an experienced
      microsurgeon should be consulted to choose between replantation and an
      alternative reconstructive procedure.

PMID- 11599212
TI  - Primary and secondary microvascular reconstruction of the upper extremity.
AB  - Tissue defects of the upper extremity may result from trauma, tumor resection,
      infection, and congenital malformation. Restoration of anatomy and functional
      integrity may require microsurgical free flap transfer for coverage of bones,
      nerves, blood vessels, or tendons. Microsurgical tissue transfer also may be
      required prior to secondary reconstruction, such as tendon transfers or nerve or
      bone grafts. This article addresses indications for upper extremity
      reconstruction using microsurgical tissue transfer flap selection and strategies
      including primary and secondary reconstruction.

PMID- 11599213
TI  - Revision amputation achieving maximum function and minimizing problems.
AB  - Revision amputation is one of the most commonly performed operations in hand
      surgery. Despite being considered, a relatively straightforward procedure, it
      demands the full skills of the operating surgeon. Appropriate management is
      dependent upon a comprehensive understanding of hand anatomy and function, the
      ability to communicate clearly with the patient, and a repertoire of technical
      skills that allows the surgeon to select the most appropriate line of management.

PMID- 11599214
TI  - Brace and rehabilitation after replantation and revascularization.
AB  - Although most reports of the functional results of replantation at the metacarpal
      level have been poor, the author (LRS) has reported good functional results with
      the early use of the dynamic crane outrigger splint with a MCP joint extension
      block, as described in this article (Fig. 8). Promoting early protective active
      motion and blocking MP joint extension [figure: see text] help achieve a hand
      with an intrinsic-plus posture and coordinated grasping. Although this protocol
      does not show an improvement over the functional results at the wrist and distal
      forearm reported by Meyer, its use can help prevent intrinsic-minus deformity,
      which is a concern in most amputations proximal to the MCP joint, according to
      Russell et al. With this technique, the need for subsequent surgery is reduced.
      Tenolysis may be needed in some patients, but it should not be performed until 6
      months postoperatively.

PMID- 11599215
TI  - Sensory substitution in prosthetics.
AB  - Use of arm and hand prostheses may be essential for many amputees to facilitate
      activities of daily life and interaction with society. A major drawback that
      reduces the use of prostheses, however, is the lack of sensibility. Current
      strategies for sensory feedback in commercially available prostheses are based on
      force and slip sensors in the mechanical hand for independent grasp control in an
      opening and closing function. Developing principles for providing conscious
      sensibility is discussed, including new techniques where hearing is used as
      substitution for sensation based on sense substitution.

PMID- 11599216
TI  - Esthetic prostheses in minor and major upper limb amputations.
AB  - In summary, the impact and value of esthetic prostheses on amputee rehabilitation
      and their long-term use were demonstrated in this study to have no correlation
      with the severity of injury and level of amputation. All patients with traumatic
      amputation should be given equal opportunity to receive prostheses if the service
      is readily available. Whether use of prostheses is temporary or long-term, they
      help patients cope with the traumatic life experience of limb loss.

PMID- 11599218
TI  - What helps and hinders workstation consolidation.

PMID- 11599217
TI  - Hand transplantation.
AB  - The surgical techniques necessary to perform hand transplantation have been
      available for at least 25 years. In this article, the authors provide a review of
      hand transplantation, including its history, preoperative evaluation, and case
      reports. Data on transplant preparation, operation data, immunosuppression,
      rejection, immunologic assessment, and functional assessment are presented in
      easy-to-use table format.

PMID- 11599219
TI  - Why the name of the game is to train.

PMID- 11599220
TI  - [Headache concurrent with the onset of ischemic stroke].
AB  - The aim of the study was to assess the occurrence of headache in acute ischaemic
      stroke and its association with type, aetiology and localization of stroke. 342
      patients with stroke were analysed. Their average age was 70.8 +/- 13.1. Headache
      was observed in 17.8% stroke patients. There was no correlation between headache
      and size of ischaemic lesion in CT. Headache was observed in 43.1% of patients
      with small foci localized in deep structure, and in 33.3% of large cortical
      subcortical foci. The analysis between the frequency of headache and type of
      stroke according OCSP classification revealed that headache occurred
      statistically significant more frequent in POCI.

PMID- 11599221
TI  - [Familial Alzheimer's disease connected with mutation in presenilin gene 1
      (P117L)].
AB  - We describe a Polish family with Alzheimer's disease in some of its members. Two
      sisters were observed and examined--also neuropathologically in the Institute of
      Psychiatry and Neurology in Warsaw. The disease onset was in our patients at 32
      and 33 years. The first symptoms were memory loss and disorientation. Later on
      myoclonus and extrapyramidal stiffness were noted in both cases. Neurovisualizing
      examinations performed in both sisters showed diffuse brain atrophy. The symptoms
      increased rapidly and in short time (several months) the patients became mute and
      bedbound. They died at age 35 and 37 years. We were informed that the father of
      the patients suffered from very similar illness and died at age of 37 years and
      their older brother had the some symptoms and died at the age of 28 years. Post
      mortem brain examination disclosed in the both hospitalized cases diffuse atrophy
      of the cerebral hemispheres, particularly severe in the temporal lobes.
      Microscopically senile plaques of various types were found in the cortex. The
      density of the plaques was very high but Alzheimer's fibrillary degeneration was
      found occasionally only. The amyloid burden in cortex of the examined brains,
      estimated as the measure of parenchymal amyloidosis beta, was two to six-fold
      higher in most areas compared with changes in sporadic AD and Down-syndrome
      cases. DNA was isolated from blood and tissue of both cases and from blood of
      their 8 children as well. In both patients mutation in presenilin 1 (PS1) gene of
      Prol 117 Leu was found and it was discovered that 4 persons of their progeniture
      were carriers of this mutation. The described mutation causes one of the earliest
      so far reported onset and death in FAD kindreds. Presenilin isolated from both
      cases and transfected into cultures of murine neuroblastoma and human kidneys
      provoked production of beta amyloid with increased A-beta 42/40 ratio.

PMID- 11599222
TI  - [Intravascular embolization of intracranial aneurysms].
AB  - The paper presents indications for and the technique of the intravascular
      procedures as well as the results of treating patients with intracranial
      aneurysms. MATERIAL AND METHOD: Between 1997 and the May 2000, 25 patients (14
      women and 11 men) with cerebral aneurysms underwent intravascular embolisation.
      The aneurysms were embolised with MDS-N BALT with coils. In 5 patients with
      aneurysm (about 2 cm), the procedure was performed in two or three steps.
      RESULTS: Aneurysms were embolised successfully in 19 patients. Three patients
      revealed intra- and postoperative complication manifestations. CONCLUSIONS:
      Intravascular embolisation of intracranial aneurysms is an affective treatment
      modality. It carries, though, a certain risk of complication development. Using
      this method in neurosurgically non-operable cases is a method of choice.

PMID- 11599223
TI  - [Social and economic aspects of administration of new antiepileptic drugs].
AB  - The necessity of analysis of the cost of treatment of patients with epilepsy
      becomes of primary importance in Poland as a consequence of recent economic
      transformations affecting the efficiency of health service. The reasons are: high
      number of patients with epilepsy (approaching 400,000 in a population of about 40
      mln) and long time course of illness, taking into account steady, gradual rise of
      the cost of treatment, even if we accept greater efficiency of the new
      antiepileptic drugs. However, the analysis of questionnaires provided by patients
      with epilepsy indicates that optimation of their treatment with introduction of
      new antiepileptic drugs may be a procedure leading to diminution of the global
      expenses associated with care of epileptic patients. Identification of factors
      influencing cost of antiepileptic treatment before and after introduction of new
      antiepileptic drugs. A group of 150 people chosen at random from a population of
      persons taking new antiepileptic drugs (vigabatrin, lamotrygin, topiramate,
      gabapentin, tiagabine) received anonymous questionnaires concerning the time
      course of their illness. 80 questionnaires were returned. The questions concerned
      the situation before and after treatment. Statistical analysis included t test
      for dependent samples-including items such as: number of epileptic seizures and
      number and days of hospitalization, etc. per year of observation. Significant
      decrease of the number of epileptic seizures (p < 0.05), number of
      hospitalizations (p < 0.001), days of hospitalizations (p < 0.001) and
      neurological consultations (p < 0.001) occurred after optimalization of
      treatment. Results of our research illustrate significant reduction of direct
      costs of treatment associated with introduction of new antiepileptic drugs.

PMID- 11599224
TI  - [Diagnosis and operative treatment of spinal metastases].
AB  - Metastases remarkable outnumber primary tumours of the spine. Approximately 70%
      of all tumours of the vertebral column are metastatic. Because of high incidence,
      fatal consequences and difficulties of treatment they present one of the most
      difficult problems in spinal pathology. The main purpose of operative treatment
      is prevention of para- or tetraplegia and pain control to extend patient's
      ability for independent live. Investigations contributing to the diagnosis and
      operative options are considered on the basis of authors' experience.

PMID- 11599225
TI  - [Dynamics of cerebral circulation on the basis of transcranial Doppler
      ultrasonography evaluation in patients with moderate and minor head injury].
AB  - Patients with moderate and minor head injury were evaluated with transcranial
      Doppler ultrasonography (TCD) and the relationship was studied between traumatic
      vasospasm (TVSP) and hyperaemia and the patients' age, clinical state, head CT
      examination and long-term results of treatment. The group examined consisted of
      45 patients. The results obtained in this group were compared with the results in
      the control group. TVSP was observed in about 20% while hyperaemia occurred in
      25% of the cases. Traumatic vasospasm in transcranial Doppler ultrasonography was
      found to occur most often in the group of patients with subdural or intracerebral
      haematomas.

PMID- 11599226
TI  - [Spinal muscular atrophy: SMN protein deficiency].
AB  - Spinal muscular atrophy is a heterogeneous group of disorders characterised by
      the loss of alfa motor neurons in spinal cord. Autosomal recessive infantile and
      juvenile proximal spinal muscular atrophy is the most common form of the disease.
      The identification of the disease gene-Survival of Motor Neuron (SMN) was a major
      advance in understanding of the molecular basis of SMA. 98% of SMA patients show
      the homozygous absence of at least exon 7 telomeric copy of SMN, the rest carry
      small intragenic mutations, usually in exon 6. Two different mechanisms seem to
      be responsible for the absence of the telomeric copy: deletion in severe form and
      gene conversion associated with mild phenotype. Recently, biochemical studies
      resulted in identification of the 38kDa survival motor neuron (SMN) protein,
      probably involved in the biogenesis of spliceosomal snRNP. The SMN protein level
      was shown to be 100-fold reduced in spinal cord of SMA 1 patients.

PMID- 11599227
TI  - [Magnesium sulphate in the treatment of ischemic-hypoxic neonatal
      encephalopathy].
AB  - Hypoxic-ischaemic encephalopathy (HIE) remains one of the most important
      neurological complications in full and near full term newborns. During HIE
      glutamate and other excitatory neurotransmitters are released and progressive
      energy failure in brain is observed. Toxicity of glutamate plays the main role in
      brain injury. Glutamate activates the specific receptors that, in turn, mediate
      an overwhelming influx of calcium into the postsynaptic neuron. The pathological
      changes are located particularly in hippocampus. Magnesium sulfate has been used
      safely for years to treat preclampsia. The animal experimental evidence support a
      neuroprotective role for magnesium in HIE.

PMID- 11599228
TI  - [Economic aspects of drug-resistant epilepsy].
AB  - Drug-resistant epilepsy is a serious source of indirect and direct public
      expenses. American studies have shown that the total cost per patient of treating
      drug-resistant epilepsy is 138,600 USD a year whereas the annual cost of treating
      effectively-treated epilepsy is 4,272 USD. Although the proportion of drug
      resistant cases does not exceed 20% of all registered cases of epilepsy these
      cases are responsible for 48% of the total direct costs and 90% of indirect costs
      of treatment. Frequent hospitalizations and introduction of more and more
      complicated polytherapies contribute to the increase in direct costs whereas the
      main factor responsible for indirect costs is the incapacity to work. Open
      clinical studies on the optimization of antiepileptic treatment have shown that a
      considerable number of patients are still diagnosed as apparently drug-resistant.
      In the case of these patients frequent modification of the methods of treatment
      are associated with patients' justified or unjustified fear of the adverse
      effects of antiepileptic drugs. This leads to mood deterioration in the patients
      themselves and, as a consequence, to poorer quality of life of the patients and
      their families. Another serious economic problem is the presence of psychogenic
      pseudo-epileptic seizures. The factors discussed in this article increase the
      measurable and immeasurable psycho-social costs of epileptic seizures.

PMID- 11599229
TI  - [Vasospasm, part I: clinical symptomatology and differential diagnosis].
AB  - Vasospasm is the most dangerous and common complication of subarachnoid
      haemorrhage (SAH) from ruptured brain aneurysms. The frequency of vasospasm is
      between 11 to 72% of SAH cases. One of the consequences of vasospasm is delayed
      neurological deficit (DND). Clinical diagnosis of vasospasm can course many
      diagnostic and therapeutic problems. This paper reviews the current developments
      concerning history, clinical picture and differential diagnosis of vasospasm.

PMID- 11599230
TI  - [Spinal cord anchored at S2 level: diagnosis difficulties and risks].
AB  - Anchoring of spinal cord at S2 level is described in a female patient aged 46,
      associated with bilateral equinovarus deformity and spina bifida in lumbar
      segment. The onset of the disease was sudden due to prolapse of intervertebral
      disc at L2-L3 and L3-L4 levels followed by bilateral flaccid-spastic paraparesis.
      In view of congenital spinal deformity lumbar tap was abandoned and MRI was
      carried out which showed spinal cord reaching down to S2 level. Diagnostic and
      therapeutic management is described and literature review is presented.

PMID- 11599231
TI  - [A case of radionecrosis of the pituitary gland region mimicking brain tumor.
      Case report].
AB  - A case is presented of delayed radiation necrosis of the pituitary gland region
      which appeared 2 years after tonsillar carcinoma surgery, followed by
      radiotherapy, in a 62-year old woman. Magnetic resonance imaging suggested the
      presence of an adenoma, metastases or craniopharyngioma, of the pituitary gland
      region. The lesion was resected, totally, using the fronto-orbital approach.
      Histopathological examination showed radionecrosis of the neurohypophysis. The
      patient was released from the hospital in a good health condition without
      neurologic deficits. On the basis of our case and reports of other authors, we
      can conclude that complications may arise as a result of radiation damage to
      neighbouring structures and there is also potential to induce malignant disease.

PMID- 11599232
TI  - [Response to the letter of Ryszard Krawiec, M.D. published in No. 5/2000 of
      Neurol. Neurochir. Pol].

PMID- 11599233
TI  - [Report on neurosurgical "Winter Meeting 2001", EANS, Vienna, 15-18.02.2001].

PMID- 11599234
TI  - [Professional responsibility of Polish scientists].
AB  - Scientist gynecologist it is not only recognized by scientific title clever man,
      but first of all--physician, who's first obligation is not to harm and--just next
      -to treat! It is not easy task in the presence of still increasing overproduction
      of medically useful informations, before which the tradition considering as a
      practiced list of rules and proceedings in chosen physician's speciality or only
      performed in regionals schools takes still greater meaning. The tradition cannot
      be separated from Polish society with its the most widely understanding
      conditions. Unfortunately on Polish market foreign handbooks have appeared, in
      which generally known but passed over in silence facts, presented in this paper,
      are not included. If this fact didn't bring harm to Polish women I wouldn't lay
      the blame on Polish scientists. Professional obligation of teachers is to get
      acquainted with handbooks available for gynecologists at large what results as
      well from standing in the society for benefit of which the profession is
      exercised as from primary complying with moral physician's responsibility.
      Finally, about the level of professional responsibility decide the results of our
      the most generally understanding medical activity, but not reached titles and
      positions.

PMID- 11599236
TI  - [Intrauterine death of one fetus during the first trimester in multiple
      gestation].
AB  - This study is a prospective review of 136 multiple gestations identified
      sonographically in the first trimester. Of these, 35 (25.7%) demonstrated the
      "vanishing twin" phenomenon, often with associated bleeding. The prognosis for
      the remaining fetus/fetuses was a good in dichorionic and bad in monochorionic
      twin pregnancy.

PMID- 11599235
TI  - [Leptin as a trigger for puberty in girls].
AB  - The influence of leptin on the serum levels of follicle stimulating hormone (FSH)
      and estradiol in girls during puberty was longitudinally studied. Two hundred and
      twenty-seven healthy girls aged from 8.8 to 15.4 years were included in the
      study. After physical examination, girls were divided into four groups according
      to pubertal development. Body fat was assessed using body mass index and the sum
      of three skin folds: at the triceps site, subscapular site and on abdomen. Serum
      concentration of leptin, FSH and estradiol were assessed by RIA methods. RESULTS:
      The mean serum concentration of leptin, FSH and estradiol increase progressively
      throughout puberty. Leptin strongly correlates with the thicknesses of the skin
      folds and BMI but small significant positive correlations were found between
      leptin and FSH as well between leptin and estradiol.

PMID- 11599237
TI  - [Gynecologic endoscopy in the greater region of Poland during 1988-1998].
AB  - The aim of the study was to analyze the state and development of the
      gynaecological endoscopy in the Wielkopolska region in years 1988-1998. The
      questionnaire included gynaecological and obstetrical departments of 31
      hospitals: 1 academic center, 5 former regional hospitals and 25 small hospitals.
      At the end of 1998 35.5% of departments were equipped with laparoscopes and 9.7%
      with histeroscopes. There was an increase in the laparoscopic procedures from 151
      to 832 estimated in these years, as well as from 181 to 314 hysteroscopies. The
      detailed analysis of procedures and dynamic of its increase according to the type
      of hospital is presented. The experience of the staff was also analyzed. We
      demonstrated the insufficient equipment in the region, in spite of the right
      tendencies in the spectrum of the endoscopic procedures and the experience of the
      physicians who perform laparoscopy and hysteroscopy.

PMID- 11599238
TI  - [Incidence of osteoporosis discovered during prophylactic tests in women from the
      Northeastern region of Poland].
AB  - In at random well-chosen group of 803 women one passed investigation of thickness
      of bone of forearm or limb not dominating. All examined were divided into two
      groups: women before menopause and after menopause. Bone mineral structure was
      estimated in individuals by thickness of osseous mass--BMD. Criteria of
      osteoporosis was coefficient T-score, which value one accepted peaceably with
      recommendations of WHO. Osteoporosis steps out considerably more often in women
      after menopause and grows together as the years go after last menstruation.

PMID- 11599239
TI  - [Risk of osteoporosis occurrence and body mass index BMI in the population of
      women of the Northeastern region of Poland].
AB  - In group 775 of women from region of north-eastern Poland, in period before and
      after menopause we estimated mass of body on the ground values of coefficient
      BMI. Values of coefficient between 18.5 and 24.9 were accepted as normal
      according to WHO. In chances of stoutness we qualified the type counting
      coefficient WHR. At all examined one passed estimation of thickness of tissue
      osseous bones of forearm. In rated frequency of occurrence of osteoporosis at
      examined women. One ascertained, that overweight and stoutness indeed puts into
      influences on lowering frequencies of occurrence osteoporosis and favors the
      maintenance correct thickness.

PMID- 11599240
TI  - [Actinomyces adnexitis in a woman].
AB  - The course of actinomycetic infections in two females with IUD is presented. Both
      patients needed surgery. Literature review taking into a special consideration
      laboratory diagnosis has been performed. Infection caused by other than
      Actinomyces israelii species was observed.

PMID- 11599241
TI  - [Transanal ultrasonography for diagnosis of obstetric anal sphincter trauma].
AB  - Fecal incontinence affects up to 2% of the general population. The major cause of
      it is related to the birth trauma of the anal sphincters. In this paper the
      possibilities of transanal endosonography in the assessment of the anal canal
      muscles defects after deliveries were presented. Anal canal sonographic anatomy
      together with the technique of the examination with the use of rotating endoprobe
      were presented. Transanal rotating endoprobe was compared with exoanal probes for
      visualization of the anal canal. Ultrasonic images of internal and external anal
      sphincters defects were shown with specific patterns of defects allowing
      differentiation between morphological and neurological damages of the sphincters.
      Anal endosonography was compared with clinical examination, electromyography and
      manometry in the assessment of the integrity of the anal sphincters.

PMID- 11599242
TI  - [Culture of human trophoblast cells in vitro as a research method--review of
      techniques (Part I)].
AB  - In part I, several histological techniques applied for establishing the human
      trophoblast cell cultures are characterized. The methods of isolation and
      purification of trophoblast cells, as well as the management of selective culture
      are discussed.

PMID- 11599243
TI  - [Culture of human trophoblast cells in vitro as a research method--review of
      techniques (Part II)].
AB  - In part II, management of the human trophoblast cell-cultures and methods of
      quality control are presented. The examples of application of this in vitro model
      for scientific research are also given.

PMID- 11599244
TI  - [Polymorphism of gene angiotensin converting enzyme in pregnancy induced
      hypertension].
AB  - In the recent years genetic background of pregnancy induced hypertension (PIH)
      are intensively investigated. Genetically determined differences in activity of
      renin-angiotensin system (RAS) are of importance to hypertension susceptibility.
      The insertion/deletion (I/D) polymorphism of angiotensin I converting enzyme
      (ACE) was suggested to play an important role in the aetiology of idiopathic
      hypertension. We have tested if this polymorphism could be associated with PIH.
      ACE polymorphism was investigated in 87 pregnant women with PIH and in 110
      healthy pregnant women (control group). Investigation was performed by polymerase
      chain reaction (PCR). We have amplified genomic DNA excteracted by phenol
      chloroform method from blood leucocytes. We have detected overrepresentation of
      the I allele in the PIH group (47.2% and 41.4% in PIH and controls,
      respectively). ACE genotype frequency in control group was in agreement with
      expected values, according to Hardy-Weinberg law, but in the PIH group the
      obtained values were different from expected. This observation confirmed the
      possible role of I allele in aetiology of PIH, and we believe that continuation
      of this investigation is necessary.

PMID- 11599245
TI  - [The analysis of caesarean sections in women residents of Bytom and in other
      women].
AB  - Authors analysed indications and number of caesarean sections performed in the I
      st Department of Obstetrics and Gynaecology in Bytom in the years 1994-1998. In
      the analyse we considered place of living of pregnant women, dividing women on
      residents of Bytom and non-residents of Bytom. The results showed increasing
      number of caesarean sections. Percentage of caesarean sections in the group of
      non-residents of Bytom was twice higher as in the group of residents of Bytom.
      The most common indications were status after prior caesarean section or other
      uterus operation, fetal distress and fetus malposition.

PMID- 11599246
TI  - [Uterus corpus extension of primary cervical carcinoma IIA-IIB].
AB  - OBJECTIVES: The infiltration of uterine body is observed in 20-43% of patients
      with primary cervical cancer in stage II. MATERIALS AND METHODS: A hystoclinical,
      retrospective analysis of 175 patients with IIA-IIB cervical carcinoma, on whom
      Wertheim-Meigs surgery was performed between 1972-1991, was done. Infiltration of
      the uterine corpus was observed in 35 patients. The presence and depth of
      extension of uterine corpus infiltration, presence of metastatic lymph nodes,
      vascular invasion and uterine vascular emboli as well as fornical and paramertial
      infiltration were assessed with regard to 5-year survival. RESULTS: It was found
      that evaluation of uterine corpus infiltration, based on our scale of depth and
      extension is useful for prognosis of patients (p < 0.001). CONCLUSION: In stage
      II of primary cervical cancer deep and extensive uterine corpus infiltration is
      an independent and detrimental prognostic factor.

PMID- 11599247
TI  - [Uterine corpus extension of primary cervical carcinoma IIA-IIB. The
      compatibility of preoperative and postoperative diagnosis and its annual
      significance].
AB  - OBJECTIVE: Evaluation of the concordance of preoperative diagnosis, based on
      dilatation and curettage (D&C) and postoperative diagnosis, based on specimen of
      uterine corpus, as well as finding if the material from D&C allows to conclude
      about extension of uterine corpus infiltration and thus patient's prognosis.
      MATERIAL AND METHODS: Analysis was done on 43 patients with uterine corpus
      infiltration in stage Ib-IIb of primary cervical cancer, on whom Wertheim-Meigs
      surgery was performed. Depth of uterine invasion in D&C material (free of cancer
      endometrium, cancerous endometrium, cancerous fragments of myometrium) was
      compared with actual postoperative assessment of uterine specimen. 5-year
      survival rate was also analysed. RESULTS: Statistically significant differences
      in depth and extension of uterine body infiltration between patients with soley
      endometrial infiltration and patients with infiltrated fragments of myometrium in
      D&C material were found. CONCLUSION: Presence of infiltrated fragments of
      myometrium in D&C material was mostly found in cases of extensive corpus
      infiltration (postoperative specimen) and it had much to do with poor prognosis.

PMID- 11599248
TI  - [The beta-hCG subunit, CA 125 and CA 19-9 antigen in the women with non
      trophoblastic malignancy of genital tract].
AB  - OBJECTIVES: The aim of this study was preoperative estimation of serum level
      glicoprotein--CA 125, CA 19-9 and beta-hCG in ovarian tumors and comparison
      obtained values in groups divided according to postoperative pathologic
      examination. MATERIALS AND METHODS: In every patients with ovarian tumors before
      surgery the level above mentioned antigens was evaluated and compared in
      following groups: malignant, non-malignant and controls. In control group cut-off
      values was estimated. RESULTS: The levels of all investigated glycoproteins were
      significantly higher in malignant group comparing to benign and controls. The
      test differentiating non-malignant from malignant tumors was accepted as positive
      if at least one from markers level was elevated. Specificity of the test was 70%,
      sensitivity--94%, positive prognostic value--74%, negative prognostic value--94%.
      In the selected subgroups from non-malignant tumors the serum level of all
      glycoproteins was surprisingly high. CONCLUSIONS: Preoperative estimation of CA
      125, CA 19-9 and beta-hCG subunit in ovarian tumors permits--at negative result-
      with probability 93% to qualify tumor as non-malignant and sensitivity of test is
      94%.

PMID- 11599249
TI  - [Pathologies observed in barium enema examination in patients with gynecological
      disorders].
AB  - The aim of our study was to analyse retrospectively 171 patients with
      gynaecological diseases, who have undergone barium enema examination in Third
      Teaching Hospital in Poznan between 1992 and 1998. 79 patients were diagnosed
      with ovarian tumours, in 24 cases their colon was dislocated. Stenosis was
      detected in 20 women and in five situations inflammatory changes of the colon
      were present. Malignant infiltration of large intestine was suspected in ten
      patients. The second group included 24 women diagnosed with tubo-ovarian
      abscesses and adnexitis. Three of them had dislocated colons. Stenosis of large
      bowel was detected in 11 patients and inflammatory changes in 8. In the next
      group of 35 patients' myoma uteri, myometrial endometriosis and carcinoma of
      colli uteri were detected. Barium enema examination revealed that 10 women had
      dislocated colons. In the third group stenosis was detected in eight cases, two
      patients had radiological signs of cancer infiltration and twice inflammatory
      changes of the large bowel were present. Frequency of radiological changes in
      barium enema examination was evaluated in the aforementioned groups. Results were
      compared with group of 33 patients treated for endocrinological disorders,
      sterility and minor pelvis pain syndrome. Frequency of dislocation of colon was
      compared with size of changes of ovaries measured during ultrasound examination.
      Our results showed that barium enema is still an important supplementary
      examination, which can give a great deal of beneficial information concerning the
      clinical condition of the patient. This procedure is useful before surgical
      intervention especially in cases of suspected ovarian cancer. We must underline
      that the same or similar information can be obtained using other methods without
      such radiation exposure.

PMID- 11599250
TI  - [The effects of micro-laparoscopic ovarian electrocautery as a method of
      polycystic ovary syndrome treatment].
AB  - The paper concerns the treatment results of 113 women with PCO-S by laparoscopic
      (102) and microlaparoscopic (11) ovarian electrocautery. All of them were
      qualified for operation on the basis of the following criteria: menstrual cycle
      disturbances (oligo-/amenorrhoea), anovulation, hirsutism, obesity, LH/FSH ratio
      > 2 and when more than 10 follicles of < 8 mm diameter are seen in the ovary
      under theca albuginea in USG examination. During the one year after operation
      these women were observed. In the first group (patients after laparoscopy)
      ovulation occurred in 86 (84%) and pregnancy in 54 (53%); accordingly in the
      second group (women after microlaparoscopy) ovulation occurred in 9 (83%) and
      pregnancy in 4 (45%). The treatment results by microlaparoscopic and laparoscopic
      ovarian electrocautery are similar, but the method by microlaparoscopy is easier
      to carry out in selected cases.

PMID- 11599251
TI  - [The relationship between intraperitoneal adhesion index and anatomical status of
      oviductal ampullary mucosa in patients with distal tubal occlusion].
AB  - OBJECTIVES: An effort was made to verify co-relation between intraperitoneal
      adhesions and anatomy of oviductal mucosa of infertile women with distal tubal
      occlusion. MATERIALS AND METHODS: The study comprised 25 infertile women with
      distal tubal occlusion. The patients were allocated into 3 groups: A--11 women
      with the history of pelvic inflammatory disease (PID); B--9 patients with
      previous gynecological abdominal surgery; and C--5 women without PID nor surgery.
      Intraperitoneal adhesion index as well as oviductal mucosa were evaluated during
      laparoscopy and salpingoscopy. RESULTS: Women with the history of PID presented
      strong co-relation between intraperitoneal adhesions and anatomical abnormalities
      of the tubal mucosa with distal tubal occlusion. The co-relation was stronger
      then in women with previous abdominal surgery. Following the evaluation of the
      fallopian tubes, 5 out of 11 patients with history of PID, 6 of 9 women with
      history of previous surgery and all 5 without any risk factors were qualified for
      microsurgical reconstructive treatment. The remaining patients were sent for in
      vitro fertilization and embryo transfer.

PMID- 11599252
TI  - [Non-closure of the visceral peritoneum during abdominal gynecological surgery].
AB  - OBJECTIVES AND STUDY DESIGN: The analysis of influence of closure and nonclosure
      of the visceral peritoneum during abdominal gynecological surgery was done.
      MATERIALS AND METHODS: A postoperative course and late consequences (occurrence
      of adhesions) in the 427 patients were studied. There were two groups of
      patients: I group--203 patients who had visceral peritoneum closed, II group--224
      patients who had visceral peritoneum non closed. RESULTS: There were not
      significant differences in postoperative course in both groups. In the group
      where the visceral peritoneum was not closed occurrence of the adhesions was
      significantly decreased, when compared the group where the visceral peritoneum
      was closed. CONCLUSIONS: 1. Nonclosure of the visceral peritoneum doesn't
      increase the incidence of early postoperative complications. 2. Nonclosure of the
      visceral peritoneum during abdominal gynecological surgery decreased the
      incidence of adhesions. 3. Nonclosure of the visceral peritoneum prevents
      dislocation and ligation of the ureter.

PMID- 11599253
TI  - [Hematological disorder caused by a giant myoma of the uterus].
AB  - OBJECTIVES: Polycythaemia means an increase in the number of red blood cells and
      usually a corresponding increase in the haematocrit and in the quantity of
      haemoglobin. Regarding etiology, primary and secondary forms of polycythaemia can
      be distinguished. The primary form--polycythaemia vera--is caused by autonomous
      erythroblastic hyperplasia. Secondary polycythaemia--erythrocythosis--may arise
      as a consequence of erythropoietin (EP) overproduction due to tissue hypoxia.
      These changes may stimulate the EP synthesis in the kidneys. EP may also be
      produced in metaplastic cells. STUDY DESIGN: A 59-year-old woman was admitted to
      the Clinic of Haematology of the Wroclaw Medical University with a 10-years'
      history of significant increase in HB, VPRC and RBC. Physical examination showed
      an obvious plethora and a large intra-abdominal painless tumour. Laboratory data
      revealed increases in Hb, VPRC, RBC and EP. A bone marrow aspiration was normal.
      During surgery, a large leiomyoma of the uterus was found and a total
      hysterectomy was performed. Pathological examination showed the tumour to be
      fibroleiomyoma. 4 weeks after surgery Hb, VPRC, RBC and EP, all returned to
      normal levels. RESULTS: Excluding the effect of the renal compression, it can be
      concluded that erythropoietin secreted by the the tumour caused the secondary
      haematological changes.

PMID- 11599254
TI  - [Nineteen year old patient with serous ovarian tumors of low malignant potential
      with non-invasive peritoneal implants: a case report].
AB  - 10-15% of ovarian epithelial tumors are the borderline ovarian tumors (BOT-s).
      The prognosis in those cases is excellent with 5-years survival rates in the
      range of 95% in Stage I. The most of women suffering from BOT-s are young and
      they have not got any children. The distinct biology of this illness makes
      possible to change previous treatment of ovarian cancers. We are able operate the
      young women planning maternity in conservative way (uni or bilateral cystectomy,
      adnexectomy). We present a case of young woman with BOT-s with non-invasive
      peritoneal implants. The bilateral cystectomy, omentectomy and staging was done.
      At present this woman is in 16 week pregnancy with good health. This confirms
      rightness of conservative treatment in BOT-s.

PMID- 11599255
TI  - [Birth environmental modification: needs of mother and child in modern
      obstetrics].
AB  - This paper evaluates changes which all ready has been done and still are taking
      place in obstetrics according to World Health Organisation recommendations in
      relation to women's increasing expectation from obstetric hospitals and maternity
      units. The needs of parturients and theirs children are not in contrary to the
      needs of modern obstetrics. An attempt has been done to disclose concurrent
      points to work up the best obstetrics health care model after 2000 year. The
      author emphasizes that progressive technicalization in obstetrics could not
      indicate its dehumanization.

PMID- 11599256
TI  - [Vulvar vestibulitis syndrome as an important clinical problem].
AB  - Clinical problems of etiology and therapy vulvovaginitis syndrome were shown.

PMID- 11599257
TI  - [Modern potentials of high-resolution ultrasound in detection of minimal vascular
      atherosclerotic lesions (Review of literature)].

PMID- 11599258
TI  - [Role of D-dimer in diagnosis of venous thrombosis and embolism].
AB  - AIM: To analyze efficiency of semi-quantitative fast D-dimer test in diagnosis of
      deep vein thrombosis (DVT) and thromboembolism of pulmonary artery (TPA).
      MATERIAL AND METHODS: The study enrolled 42 patients (26 males and 16 females)
      aged 25 to 86 years. 30 and 12 of them were suspected to have DVT and TPA,
      respectively. DVT was verified at ultrasound dopplerography and radionuclide
      phlebography in 16 of 30 suspects. TPA was verified by x-ray, perfusion
      scintigraphy of the lungs and at autopsy (one case) in 7 of 12 suspects. D-dimer
      levels in the blood were measured by latex parts agglutination reaction. The
      parts were covered with monoclonal antibodies to D-dimer. The reagents were
      provided by the kit Roche/Diagnostica Stago. RESULTS: The D-dimer test was
      positive in 20 of 23 DVT patients and negative in 3 cases (13%). Of 19 patients
      with rejected diagnosis of DVT/TPA the test was negative in 17(89.4%) and
      positive in 2 patients (10.6%). Thus, sensitivity and specificity of the D-dimer
      test was 87% and 89.4%, respectively. CONCLUSION: High sensitivity of the test
      allows to use it in screening for DVT/TPA. Negative D-dimer test rejects DVT,
      while positive test needs verification by other methods.

PMID- 11599259
TI  - [Dobutrex stress echocardiography: clinical and prognostic value, side effects].
AB  - AIM: To study informative value of dobutrex echocardiography (DEC) in diagnosis
      of myocardial ischemia and viability, in prognostication of angina pectoris and
      myocardial infarction (MI), evaluation of DEC side effects. MATERIAL AND METHODS:
      DEC was conducted in 74 patients with unconfirmed diagnosis (they had ischemic
      heart disease risk factors, atypical cardialgia) and 32 ischemic heart disease
      patients. RESULTS: DEC proved to be an effective diagnostic tool in diagnosis of
      myocardial ischemia in patients with new-onset atypical cardialgia (informative
      value 73.6%). This test gives prognosis of the disease and improves treatment
      policy in patients with angina of effort and MI. The most serious and frequent
      side effects of DEC arising at the highest dobutrex dose were paroxysmal
      tachycardias (3.76%) and ventricular arrhythmias (6.58%). In most cases (99.1%)
      they discontinued after the test and did not require antiarrhythmic treatment.
      Thus, the test is relatively safe. CONCLUSION: Echocardiography with dobutrex
      load should be used in practical cardiology more intensively.

PMID- 11599260
TI  - [Assessment of corrected orthogonal ECG system of McFee-Parungao leads in bicycle
      exercise test in patients with myocardial ischemia].
AB  - AIM: To assess orthogonal ECG system McFee-Parungao in exercise test performed by
      patients with ischemic heart disease (IHD). MATERIAL AND METHODS: The trial
      included 103 patients: 41 patients with IHD, 23 patients with IHD combined with
      arterial hypertension and 39 control patients free of IHD. All the patients
      performed bicycle exercise with ECG registration in the corrected orthogonal
      system of leads modified according to McFee-Parungao. In 11 patients ECG was
      registered in two systems--orthogonal and standard 12-lead. Sensitivity and
      specificity in IHD were assessed. RESULTS: Parameters of the bicycle exercise
      test registered by ECG in the corrected orthogonal system indicated that
      sensitivity and specificity of this system in IHD patients are not inferior to
      sensitivity and specificity of the standard 12-lead ECG system. CONCLUSION: The
      system of orthogonal leads McFee-Parungao is recommended for use in the practice
      of bicycle exercise tests in IHD patients.

PMID- 11599261
TI  - [The current state of diagnosis in pulmonology].

PMID- 11599262
TI  - [Gastroenterology in new century: problems of diagnosis].

PMID- 11599263
TI  - [Current methods of diagnosis of gall bladder dyskinesia and acalculous
      cholecystitis].

PMID- 11599265
TI  - [Modern approaches to immunological study of human chronic inflammatory and
      autoimmune diseases].

PMID- 11599264
TI  - [Comparative diagnostic value of data of intestinoscopy with biopsy obtained from
      different regions of the small intestine].
AB  - AIM: To study diagnostic value of intestinoscopy with biopsy of the mucosa from
      different portions of the small intestine in patients with chronic diarrhea and
      malabsorption. MATERIAL AND METHODS: The examination of 116 patients with chronic
      diarrhea and malabsorption (endoscopic and histological study of biopsy specimens
      from different portions of the small intestine) detected gluten enteropathy (n =
      51), Wipple's disease (n = 8), general variable hypogammaglobulinemia (n = 11),
      lymphangioectasy (n = 9), lymphangiomatosis (n = 1), lymphoma (n = 2),
      amyloidosis (n = 3), eosinophilic gastroenteritis (n = 1), duodenoejunitis
      without atrophy (n = 7). 23 patients had normal mucosa of the small intestine.
      RESULTS: Pathological changes in the jejunum and duodenum were identical in
      glutenic enteropathy (GE), Wipple's disease (WD), variable hypogammaglobulinemia
      (VH) and amyloidosis. CONCLUSION: For diagnosis of GE, WD, VH and amyloidosis it
      is sufficient to take biopsy from distal duodenum. Spot biopsy from sites of
      lymphostasis or nodular lymphoid hyperplasia is most informative for
      identification of lymphangioectasy, lymphangiomatosis and small intestinal
      lymphoma. Pathological changes in the ileum in GE, WD, VH and amyloidosis
      indicate severe total lesion of the small intestine.

PMID- 11599266
TI  - [Ultrasound angiography: new perspectives in diagnosis of renal mass lesions].
AB  - AIM: To evaluate diagnostic efficacy of advanced ultrasound (US) techniques in
      early and differential diagnosis of malignant tumors of the kidneys. MATERIAL AND
      METHODS: A total of 394 patients with renal mass lesions were studied. They had:
      renal cell carcinoma (n = 96), renal parenchyma pseudotumors (n = 22), lipoma (n
      = 48), angiomyolipoma (n = 19), renal abscess (n = 2), renal sinus lipomatosis (n
      = 1), parenchymal cysts (n = 205), retroperitoneal leiomyosarcoma with invasion
      in the kidney (n = 1). The following examinations were made: gray scale study
      with tissue harmonic imaging, panoramic scanning, US-angiography (color doppler
      imaging--CDI, power doppler imaging--PDI, 3D-reconstruction of the kidney
      vessels, 3D dynamic contrast enhanced angiography (DCEA) in the second harmonic
      mode with an echo-contrast agent levovist. Pulse Doppler with qualitative and
      quantitative evaluation of the doppler spectrum was used as an additional method.
      Verification of the diagnosis was made by conventional angiography, computer
      tomography, MR-tomography, histomorphological analysis after surgery in 91, 310,
      6 and 88 patients, respectively. RESULTS: New US techniques allow differentiation
      of malignant tumors with renal lipomas and angiomyolipomas, focuses of
      inflammation, pseudotumors of the renal parenchyma and atypical renal cysts. CDI
      has revealed big pathologic vessels with arterio-venous and arterio-arterial
      shunts in renal cancer in 63.5% of the cases. PDI visualized a net of
      pathologically changed vessels in 74.8% of the cases. 3D-reconstruction in PDI
      was highly sensitive (90%) in visualization of neoplastic vessels. US-angiography
      was used for pre- and postoperative monitoring in 18 patients subjected to
      conservative renal surgery. In 23 patients DCEA with levovist allowed monitoring
      of all phases of contrast enhancement of renal vessels. Injection of contrast
      agent revealed tumor microvasculature in an early arterial phase (20-30 seconds).
      CONCLUSION: US-angiographic techniques in diagnosis of renal cancer increases
      sensitivity and specificity of the US method compared to conventional B-mode US
      from 55 and 60% to 98 and 95%, positive and negative predictive value from 58 and
      57% to 95 and 98%, respectively.

PMID- 11599267
TI  - [Diagnosis in XXI century. From subjective to objective].

PMID- 11599268
TI  - [Diagnosis of parvovirus B19 infection in hematological patients with partial red
      cell aplasia of the bone marrow].
AB  - AIM: To assess diagnosis of parvovirus B19 infection (PI) in patients with
      aplastic crises by combined use of polymerase chain reaction (PCR) and enzyme
      immunoassay (EIA) of specific IgM and IgG. MATERIAL AND METHODS: A total of 159
      serum samples from 77 PI suspects were examined. The examination for virus DNA
      was conducted with modified "net" PCR in 108 samples, for specific IgM and IgG
      with EIA in 110 samples. RESULTS: The percentage of patients infected with
      parvovirus detected by PCR or EIA reached 60%. 21 of 77 patients with hemolytic
      anemias were infected with parvovirus B19, the virus persisting in 8 cases (40%).
      persistence of the virus was registered if viremia occurred in immunodeficiency
      due to the disease or immunosuppressive therapy. Immunity to parvovirus has not
      developed: IgM expression was the same as in patients without hemopoietic
      abnormalities, while IgG was not detected. The absence of specific immunity to
      parvovirus B19 occurred in patients treated with immunosuppressive drugs early
      after the end of viremia period in high IgM level and at the initial phase of IgG
      synthesis. IgM levels also remained unchanged; the level of IgG declined and was
      not identified furthermore. There were cases of reinfection. CONCLUSION: Combined
      use of PCR and EIA is optimal for diagnosis of parvovirus B19 infection in
      patients with hemolytic anemias. It was found that there are correlations between
      defects in specific immunity, persistence and immunodeficiency onset regarding
      viremia. Abnormal for the disease course levels of IgM and IgG indicate the
      persisting virus, the condition of specific immune response to parvovirus B19 and
      feasibility of reinfection. Reliable diagnosis of parvovirus infection is
      possible only in simultaneous use of PCR and EIA.

PMID- 11599269
TI  - [Correction of coronary insufficiency by dihydropiridine antagonists of calcium
      in patients with coronary artery bypass].
AB  - AIM: To study antiischemic and antianginal efficiency of adalat and its prolonged
      form adalat SL, dihydropiridin antagonists of calcium, in patients 1-3 years
      after surgical correction of stenosing coronary atherosclerosis. MATERIAL AND
      METHODS: The drugs were tried in 40 patients with angina of effort (functional
      class II-III) with a satisfactory inotropic function of the left ventricle 1 to 3
      years after coronary artery bypass surgery (CABS). Myocardial circulation was
      measured with one-photon emission computed tomography using 99m-Tc-MIBI (CT).
      RESULTS: A 3-week therapy with adalat reduced the number of anginal attacks,
      nitroglycerin requirement, enhanced exercise tolerance. CT showed that myocardial
      blood flow significantly improved. CONCLUSION: Adalat proved to be effective in
      patients after CABS. Its prolonged form adalat SL is preferable.

PMID- 11599270
TI  - [Economic assessment of efficacy of vasaprostan treatment of critical lower limbs
      ischemia].
AB  - AIM: To estimate cost-effect efficacy of vasaprostan treatment of inpatients with
      arterial chronic obliteration (ACO) with critical ischemia of the lower limbs
      (Fonten stage III-IV). MATERIAL AND METHODS: Case histories of 105 ACO patients
      with critical ischemia of the lower limbs (mean age 65 +/- 11.8 years) were
      analysed to compare efficacy and cost of the "typical practice" of hospital
      treatment of such patients with prognostic cost of basaprostan treatment using
      drug-cost modeling. RESULTS: The cost-effect analysis comparing efficacy of
      "typical practice" and vasaprostan treatment showed that in "typical practice"
      amputations of the limb are inevitable in 41% while vasaprostan treatment reduces
      the percentage of the operations to 8.6-12% (according to the literature);
      overall cost of the "typical" treatment for 105 patients reached 3,909,222
      roubles while relevant prognostic cost of vasaprostan treatment made up 4,407,162
      4,570,653 roubles. Thus, vasaprostan treatment is characterized by less expense
      per 1 case of the limb amputation prevention vs "typical practice". CONCLUSION:
      The models used demonstrated that vasaprostan treatment is more cost-effective
      than "typical practice".

PMID- 11599271
TI  - [Clinico-laboratory assessment of oframax (cefriaxone) in the treatment of
      infectious-inflammatory diseases].
AB  - AIM: To try efficacy and safety of ophramax (cephtriaxon) made in India
      ("Ranbaxy") in infectious-inflammatory diseases treated in a general hospital.
      MATERIAL AND METHODS: Ophramax was given in a dose 1 to 4 g/day to 23 patients
      with pneumonia, chronic bronchitis, soft tissue infection, enterocolitis, etc.
      Therapeutic effect was examined with bacteriological identification of the
      infective agents, antibioticograms, agar diffusion test. RESULTS: High
      sensitivity of pathogens to ophramax was observed in bronchopulmonary diseases
      (90.7%). In other infections sensitivity of the pathogens was 59.3%. Enterococci
      were the only highly resistant pathogens (40.5%). Ophramax remains in the body in
      sufficiently high concentrations for 24 hours. This attributes to good
      therapeutic effect. CONCLUSION: Clinico-microbiological and pharmacokinetic
      findings show that ophramax can be used as a basic drug for treatment of
      different infectious-inflammatory diseases. Once-a-day regimen is a great
      advantage of ophramax.

PMID- 11599272
TI  - [Obesity and cardiovascular diseases].

PMID- 11599273
TI  - [Freon-free inhalers--the current standard of inhalation drugs delivery].

PMID- 11599274
TI  - [How to overcome antibiotic resistance of Helicobacter pylori. Role of de-nol in
      current schemes of eradication therapy].

PMID- 11599275
TI  - [Antibiotic-related diarrhea and pseudomembraneous colitis (diagnosis and
      treatment)].

PMID- 11599276
TI  - [The role of transesophageal echocardiography in deciding the treatment patients
      with atrial fibrillation].

PMID- 11599277
TI  - [Potentials of radiation methods in non-invasive diagnosis of cardiovascular
      diseases in the beginning of the new century].

PMID- 11599278
TI  - [The role of calcium antagonists in the treatment of arterial hypertension].

PMID- 11599279
TI  - [Use of angiotensin II receptor antagonists in the treatment of patients with
      chronic heart failure].

PMID- 11599280
TI  - Responding rapidly to occupational blood and body-fluid exposures.

PMID- 11599281
TI  - Hemorrhoids, genital warts, and other perianal complaints.

PMID- 11599282
TI  - Common triggers of facial erythema in adults.

PMID- 11599283
TI  - Getting involved again--a new experience for a veteran PA.

PMID- 11599284
TI  - [Dining on delicious watercress salad. That is how he got it! ].

PMID- 11599285
TI  - [Gastroscopy only after positive Helicobacter pylori test. That has a point!].

PMID- 11599286
TI  - [The right drugs for panic and phobias. Managing anxiety in your patients].

PMID- 11599287
TI  - [Allergy caused by excessive cleanliness. Dog keeps asthma at bay].

PMID- 11599288
TI  - [Hypertensive emergency. Initiating therapy already in general practice].

PMID- 11599289
TI  - [Angina pectoris emergency. Ambulatory assessment or patient admission?].
AB  - Provision of medical help for acute angina pectoris must take its cue from the
      severity of the symptoms and the probability that coronary artery disease
      actually is present. The therapeutic possibilities range from clarification of
      the situation in the office to immediate initiation of treatment and
      hospitalizing the patient in the company of an emergency physician. In addition
      to changes in lifestyle and diet, treatment options for coronary artery disease
      include the elimination of risk factors, symptomatic treatment with nitrates,
      molsidomine, beta blockers, and calcium antagonists, percutaneous transluminal
      coronary angioplasty and coronary artery bypass surgery.

PMID- 11599290
TI  - [Emergency care in acute left heart failure. Decreasing preload, oxygen
      inhalation].

PMID- 11599291
TI  - [Conservative therapy of severe ulcerative colitis. More effective than
      internists believe!].

PMID- 11599292
TI  - [Proper diagnosis of dizziness. Nystagmus--the key in vertigo].

PMID- 11599293
TI  - [Type 1, type 2 diabetes, MODY and LADA. Making a differential diagnosis].

PMID- 11599294
TI  - [Intermittent atrial fibrillation. An "idiopathic" emergency. Torsade de
      pointes].

PMID- 11599295
TI  - [Subjective wellbeing in heroin withdrawal. With methadone the patient feels
      better].

PMID- 11599296
TI  - [Gluteal pruritus... Not necessarily a mycotic etiology and especially don't
      recommend camomile baths!].

PMID- 11599297
TI  - Neurosteroids: beginning of the story.
AB  - Neurosteroids are synthetisized in the central and the peripheral nervous system,
      in glial cells, and also in neurons, from cholesterol or steroidal precursors
      imported from peripheral sources. They include 3 beta-hydroxy-delta 5-compounds,
      such as pregnenolone (PREG) and dehydroepiandrosterone, their sulfate esters, and
      compounds known as reduced metabolites of steroid hormones, such as the
      tetrahydroderivative of progesterone 3 alpha-hydroxy-5 alpha-pregnan-20-one.
      These neurosteroids can act as modulators of neurotransmitter receptors, such as
      GABAA, NMDA, and sigma 1 receptors. Progesterone itself is also a neurosteroid,
      and a progesterone receptor has been detected in peripheral and central glial
      cells. At different sites in the brain, neurosteroid concentrations vary
      according to environmental and behavioral circumstances, such as stress, sex
      recognition, or aggressiveness. A physiological function of neurosteroids in the
      central nervous system is strongly suggested by the role of hippocampal PREGS
      with respect to memory performance, observed in aging rats. In the peripheral
      nervous system, a role for PROG synthesized in Schwann cells has been
      demonstrated in remyelination after cryolesion of the sciatic nerve in vivo and
      in cultures of dorsal root ganglia. A new mechanism of PREG action discovered in
      the brain involves specific steroid binding to microtubule associated protein and
      increased tubulin polymerization for assembling microtubules. It may be important
      to study the effects of abnormal neurosteroid concentration/metabolism in view of
      the possible treatment of functional and trophic disturbances of the nervous
      system.

PMID- 11599298
TI  - Role of the peripheral-type benzodiazepine receptor in adrenal and brain
      steroidogenesis.
AB  - The peripheral-type benzodiazepine receptor (PBR) has been demonstrated to be
      critical for steroidogenesis in all steroid-producing tissues. Here, we review
      the identification and characterization of the PBR, the evidence pointing to its
      function as a cholesterol pore involved in transporting cholesterol from the
      cytoplasm of steroid-producing cells into the inner mitochondrial membrane where
      it is metabolized, and the known mechanisms regulating its function. We present
      data on the functions of the PBR in the adrenal gland, a classical steroidogenic
      tissue, and in the brain, which has only recently been proven to be
      steroidogenic. Finally, we discuss other potential roles for the PBR in
      pathological conditions, including cancer, neurodegeneration, and neurotoxicity,
      and a broader role for the PBR in mediating intracellular cholesterol
      transport/compartmentalization, which may or may not be linked to steroid
      biosynthesis.

PMID- 11599299
TI  - Formation and effects of neuroactive steroids in the central and peripheral
      nervous system.
AB  - This chapter summarizes several observations that emphasize the importance of
      neuroactive steroids in the physiology of the central and peripheral nervous
      systems. A new, and probably important, concept is emerging: Neuroactive steroids
      not only modify neuronal physiology but also intervene in the control of glial
      cell functions. The data presented here underscore that (1) the mechanism of
      action of the various steroidal molecules may involve both classical
      (progesterone and androgens) and nonclassical steroid receptors [gamma
      aminobutyric acid type A (GABAA) receptor], (2) in many instances, the actions of
      hormonal steroids are not due to their native molecular forms but to their 5
      alpha- and 3 alpha,5 alpha-reduced metabolites, (3) several neuroactive steroids
      exert dramatic actions on the proteins proper of the peripheral myelin (e.g.,
      glycoprotein Po and peripheral myelin protein 22), and (4) the effects of
      steroids and of their metabolites might have clinical significance in cases in
      which the rebuilding of the peripheral myelin is needed (e.g., aging, peripheral
      injury).

PMID- 11599300
TI  - Neurosteroid modulation of recombinant and synaptic GABAA receptors.
AB  - Certain pregnane steroids are now established as potent, positive allosteric
      modulators of the gamma-aminobutyric acid type A (GABAA) receptor. These
      compounds are known to be synthesized in the periphery by endocrine glands, such
      as the ovaries and the adrenal glands, and can rapidly cross the blood-brain
      barrier. Therefore, such steroids could act as endogeneous modulators of the
      major inhibitory receptor in the mammalian central nervous system. However, the
      demonstration that certain neurons and glia can synthesize the pregnane steroids
      (i.e., neurosteroids) additionally suggests that they may serve a paracrine role
      by influencing GABAA-receptor function through their local release in the brain
      itself. Here, we demonstrate that these neurosteroids are highly selective and
      extremely potent modulators of the GABAA receptor. The subunit composition of the
      GABAA receptor may influence the actions of the neurosteroids, particularly when
      considering concentrations of these agents thought to occur physiologically,
      which may underlie their reported differential effects at certain inhibitory
      synapses. However, recent work suggests that the phosphorylation status of either
      the synaptic GABAA receptor or its associated proteins may also influence
      neurosteroid sensitivity; these findings are discussed. Upon administration, the
      neurosteroids exhibit clear behavioral effects, including sedation,
      anticonvulsant actions, and behaviors predictive of anxiolysis; when given at
      high doses, they induce general anesthesia. Numerous synthetic steroids have been
      synthesized in an attempt to therapeutically exploit these properties, and these
      data are reviewed in this chapter. However, targeting the brain enzymes that
      synthesize and metabolize the neurosteroids may offer a new approach to exploit
      this novel endocrine-paracrine neurotransmitter interaction.

PMID- 11599301
TI  - GABAA-receptor plasticity during long-term exposure to and withdrawal from
      progesterone.
AB  - The subunit composition of native gamma-aminobutyric acid type A (GABAA)
      receptors is an important determinant of the role of these receptors in the
      physiological and pharmacological modulation of neuronal excitability and
      associated behavior. GABAA receptors containing the alpha 1 subunit mediate the
      sedative-hypnotic effects of benzodiazepines (Rudolph et al., 1999; McKernan et
      al., 2000), whereas the anxiolytic effects of these drugs are mediated by
      receptors that contain the alpha 2 subunit (Low et al., 2000). In contrast, GABAA
      receptors containing the alpha 4 or alpha 6 subunits are insensitive to
      benzodiazepines (Barnard et al., 1998). Characterization of the functions of
      GABAA-receptors thus requires an understanding of the mechanisms by which the
      receptor subunit composition is regulated. The expression of specific GABAA
      receptor subunit genes in neurons is affected by endogenous and pharmacological
      modulators of receptor function. The expression of GABAA-receptor subunit genes
      is thus regulated by neuroactive steroids both in vitro and in vivo. Such
      regulation occurs both during physiological conditions, such as pregnancy, and
      during pharmacologically induced conditions, such as pseudo-pregnancy and long
      term treatment with steroid derivatives or anxiolytic-hypnotic drugs. Here, we
      summarize results obtained by our laboratory and by other groups pertaining to
      the effects of long-term exposure to, and subsequent withdrawal from,
      progesterone and its metabolite 3 alpha,5 alpha-tetrahydroprogesterone on both
      the expression of GABAA-receptor subunits and GABAA-receptor function.

PMID- 11599302
TI  - Stress and neuroactive steroids.
AB  - The discovery that the endogenous steroid derivatives 3 alpha-hydroxy-5 alpha
      pregnan-20-one (allopregnanolone, or 3 alpha,5 alpha-TH PROG) and 3 alpha,21
      dihydroxy-5 alpha-pregnan-20-one (allotetrahydrodeoxycorticosterone, or 3 alpha,5
      alpha-TH DOC) elicit marked anxiolytic and anti-stress effects and selectively
      facilitate gamma-aminobutyric acid (GABA)-mediated neurotransmission in the
      central nervous system (see Chapter 3) has provided new perspectives for our
      understanding of the physiology and neurobiology of stress and anxiety. Evidence
      indicating that various stressful conditions that downregulate GABAergic
      transmission and induce anxiety-like states (Biggio et al., 1990) also induce
      marked increases in the plasma and brain concentrations of these neuroactive
      steroids (Biggio et al., 1996, 2000) has led to the view that stress,
      neurosteroids, and the function of GABAA receptors are intimately related.
      Changes in the brain concentrations of neurosteroids may play an important role
      in the modulation of emotional state as well as in the homeostatic mechanisms
      that counteract the neuronal overexcitation elicited by acute stress. Indeed,
      neurosteroids not only interact directly with GABAA receptors but also regulate
      the expression of genes that encode subunits of this receptor complex. This
      chapter summarizes observations from our laboratories and others, suggesting that
      neurosteroids and GABAergic transmission are important contributors to the
      changes in emotional state induced by environmental stress.

PMID- 11599303
TI  - Neurosteroids in learning and memory processes.
AB  - The discovery that neurosteroids could be synthesized de novo in the brain
      independent from the periphery and display neuronal actions led to great
      enthusiasm for the study of their physiological role. Pharmacological studies
      suggest that neurosteroids may be involved in several physiological processes,
      such as learning and memory. This chapter summarizes the effects of the
      administration of neurosteroids on learning and memory capabilities in rodents
      and in models of amnesia. We address the central mechanisms involved in mediating
      the modulation of learning and memory processes by neurosteroids. In this regard,
      the neurosteroid-modulated neurotransmitter systems, such as gamma-aminobutyric
      acid type A, N-methyl-D-aspartate, and cholinergic and sigma opioid systems,
      appear to be potential targets for the rapid memory alteration actions of
      neurosteroids. Moreover, given that some neurosteroids affect neuronal
      plasticity, this neuronal change could be involved in the long-term modulation of
      learning and memory processes. To understand the role of endogeneous
      neurosteroids in learning and memory processes, we present some physiological
      studies in rodents and humans. However, the latter do not successfully prove a
      role of endogenous neurosteroids in age-related memory impairments. Finally, we
      discuss the relative implication of a given neurosteroid vs its metabolites. For
      this question, a new approach using the quantitative determination of traces of
      neurosteroids by mass spectrometry seems to have potential for examining the role
      of each neurosteroid in discrete brain areas in learning and memory alterations,
      as observed during aging.

PMID- 11599304
TI  - Neurosteroids and behavior.
AB  - Neurosteroid production may be a mechanism to counteract the negative effects of
      stress and return organisms toward homeostasis. Stress induces an increase in
      neurosteroid production. Neurosteroids affect two of the most widely distributed
      neurotransmitter and receptor systems in the central nervous system (CNS): gamma
      aminobutyric acid (GABA) and glutamate. This ability of this class of compounds
      to affect both the primary excitatory and the inhibitory systems in the CNS
      allows the modulation of a wide array of behaviors. For example, neurosteroids
      modulate anxiety, cognition, sleep, ingestion, aggression, and reinforcement. In
      general, neurosteroids that are positive modulators of N-methyl-D-aspartate
      receptors enhance cognitive performance and decrease appetite. Neurosteroids that
      are positive modulators of GABAA receptors decrease anxiety, increase feeding and
      sleeping, and exhibit a bimodal effect on aggression that may be secondary to
      effects on anxiety and cognition. Some data suggest that neurosteroids have
      reinforcing effects, which could affect their clinical utility. Drug
      discrimination studies are helping scientists to dissect more closely the
      receptor systems affected by neurosteroids at the behavioral level.

PMID- 11599305
TI  - Biosynthesis of neurosteroids and regulation of their synthesis.
AB  - The brain, like the gonads, adrenal glands, and placenta, is a steroidogenic
      organ. The steroids synthesized by the brain and by the nervous system, given the
      name neurosteroids, have a wide variety of diverse functions. In general, they
      mediate their actions not through classic steroid hormone nuclear receptors but
      through ion-gated neurotransmitter receptors. This chapter summarizes the
      biochemistry of the enzymes involved in the biosynthesis of neurosteroids, their
      localization during development and in adulthood, and the regulation of their
      expression, highlighting both similarities and differences between expression in
      the brain and in classic steroidogenic tissues.

PMID- 11599306
TI  - Ethanol and neurosteroid interactions in the brain.

PMID- 11599307
TI  - Preclinical development of neurosteroids as neuroprotective agents for the
      treatment of neurodegenerative diseases.
AB  - Recent literature has emphasized the unique role that the neurosteroid subclass
      of steroids, which includes dehydroepiandrosterone (DHEA) and
      dehydroepiandrosterone sulfate (DHEAS), play in the developing and adult central
      nervous system (CNS). Both DHEA and DHEAS are found in abundance in the CNS
      (Majewska, 1995), and both can be synthesized and metabolized in the brain of
      many species (Baulieu, 1981, 1998; Corpechot et al., 1981, 1983; Zwain and Yen,
      1999). DHEA and DHEAS have been implicated as potential signaling molecules for
      neocortical organization during neuronal development, suggesting that they have
      trophic factor-like activity (neurotrophic or neurotropic) or can interact with
      various neurotransmitter systems to promote neuronal remodeling (Compagnone and
      Mellon, 1998; Mao and Barger, 1998). Consistent with a neurotrophic role for
      these steroids, studies have shown that DHEAS protects certain neuronal
      populations against neurotoxic insults inflicted by the excitatory amino acid
      glutamate (Kimonides et al., 1998; Mao and Barger, 1998). This finding suggests
      that DHEAS may be useful in treating neurodegenerative diseases in which
      excitotoxicity is believed to be the underlying cause or a major contributor to
      cell death. Moreover, because DHEA and DHEAS are multifunctional and exhibit a
      variety of properties in the CNS, including memory consolidation,
      neuroprotection, and reduction of neurodegeneration (Majewska, 1992, 1995;
      Lapchak et al., 2000), their potential therapeutic benefits may be extended to
      include the treatment of other neurodegenerative diseases not directly linked to
      excitotoxicity.

PMID- 11599308
TI  - Clinical implications of circulating neurosteroids.

PMID- 11599309
TI  - Neuroactive steroids and central nervous system disorders.
AB  - Steroid hormones are vital for the cell life and affect a number of
      neuroendocrine and behavioral functions. In contrast to their endocrine actions,
      certain steroids have been shown to rapidly alter brain excitability and to
      produce behavioral effects within seconds to minutes. In this article we direct
      attention to this issue of neuroactive steroids by outlining several aspects of
      current interest in the field of steroid research. Recent advances in the
      neurobiology of neuroactive are described along with the impact of advances on
      drug design for central nervous system (CNS) disorders provoked by neuroactive
      steriods. The theme was selected in association with the clinical aspects and
      therapeutical potentials of the neuroactive steroids in CNS disorders. A wide
      range of topics relating to the neuroactive steroids are outlined, including
      steroid concentrations in the brain, premenstrual syndrome, estrogen and
      Alzheimer's disease, side effects of oral contraceptives, mental disorder in
      menopause, hormone replacement therapy, Catamenial epilepsy, and neuractive
      steroids in epilepsy treatment.

PMID- 11599310
TI  - Neuroactive steroids in neuropsychopharmacology.
AB  - Steroids influence neuronal function through binding to intracellular receptors,
      which may act as transcription factors in the regulation of gene expression. In
      addition, certain so-called neuroactive steroids are potent modulators of an
      array of ligand-gated ion channels and of distinct G-protein-coupled receptors
      via nongenomic mechanisms. Neuroactive steroids may modulate an array of
      neurotransmitter receptors and regulate gene expression. This intracellular cross
      talk between genomic and nongenomic steroid effects provides the basis for their
      neuropsychopharmacological potential with regard to both clinical effects and
      side effects. These compounds may influence sleep and memory. Moreover, they may
      play a role in the response to stress and the treatment of neuropsychiatric
      disorders, such as epilepsy, depression, and anxiety disorders. Neuroactive
      steroids affect a broad spectrum of behavioral functions through their unique
      molecular properties and may constitute an unexploited class of drugs. However,
      particular attention must be drawn to putative side effects that are inherent to
      their molecular diversity. Moreover, it must be determined whether synthetic
      steroid compounds really offer an advantage over already known drugs and whether
      the modulation of endogenous neuroactive steroids might constitute a useful
      alternative strategy for pharmacological intervention.

PMID- 11599311
TI  - Current perspectives on the role of neurosteroids in PMS and depression.

PMID- 11599312
TI  - Neurosteroid 7-hydroxylation products in the brain.
AB  - The neurosteroids pregnenolone (PREG) and dehydroepiandrosterone (DHEA) are
      precursors for both oxidized and hydroxylated metabolites in the brain. Thus,
      brain production of 7-hydroxylated derivatives is second to that in the liver,
      and P4507B1-containing hippocampus is the major site for 7 alpha-hydroxylation.
      Other P450s and/or oxido-reductive mechanisms may be responsible for 7 beta
      hydroxylation. In addition to regulating neurosteroid brain levels, when
      produced, the 7-hydroxylated derivatives of PREG and DHEA were investigated for
      antiglucocorticoid-mediated neuroprotective potencies, and both 7 alpha- and 7
      beta-hydroxy-DHEA were efficient in preventing the nuclear uptake of
      [3H]dexamethasone-activated glucocorticoid receptor in brain cells. Activation of
      7 alpha-hydroxylation by increased close contacts of astrocytes and after
      glucocorticoid treatment suggested that the regulated production of 7 alpha
      hydroxysteroids was a key event for the neuroprotection conferred by
      neurosteroids.

PMID- 11599313
TI  - Neurosteroid analysis.
AB  - In this chapter, we review techniques used for the analysis of neurosteroids and
      discuss the advantages and disadvantages of each method. Because radioimmunoassay
      (RIA) procedures are well known, we focus more on the relatively recent mass
      spectrometric methods used for analyzing neurosteroids and their sulfates. We
      also discuss some promising methods that permit the detection of low levels of
      neurosteroids in small samples with a minimum number of sample pretreatment
      procedures. Lowering the limits of detection will enable a better understanding
      of the physiological function of neurosteroids and the mechanism(s) for
      neurosteroid regulation of brain function. Moreover, analyzing low levels of
      neurosteroids more efficiently will increase the throughput, which is important
      for clinical analysis. Initially, most neurosteroid analyses were performed by
      RIA. However, many analyses of neurosteroids are now performed by mass
      spectrometry. To date, the most sensitive, specific, and accurate method for the
      simultaneous analysis of several neurosteroids is the method of gas
      chromatography/electron capture/negative chemical ionization mass spectrometry.
      This method, with its many variants, is described in detail.

PMID- 11599314
TI  - [Effect of hormone replacement with tibolone on plasma insulin and blood glucose
      in postmenopause].
AB  - The effect of Tibolone, and estrogen-like therapeutic agent used for menopause,
      on insulin and glucose was investigated in 18 healthy postmenopausal women. At
      baseline and after 3 months of Tibolone, 2.5 mg daily, blood levels of glucose
      and insulin were evaluated in each participant. Fasting levels of glucose were
      not modified by Tibolone, whereas plasmatic insulin levels were reduced
      significantly (p < 0.01). High-density lipoprotein cholesterol and total
      cholesterol were not affected by Tibolone. From these data it may be suggested
      that Tibolone does not negatively influence glucose fasting levels, but reduces
      the already elevated insulin levels which may be due to an improvement in
      peripheral tissue sensitivity to insulin.

PMID- 11599315
TI  - [Comparative analysis of multifollicular development with the application of
      recombinant FSH vs. urinary FSH in the results of in vitro fertilization].
AB  - The interactive function between intrafollicular factors related with ovum
      competence and embryo development played an important role getting high quality
      embryos during the embryo transference in in-vitro fertilization programs.
      Urinary gonadotropins are used widely to get homogeneous follicles during ovarian
      stimulation. Recombinant technology has been applied in these compounds to
      correlate with a best egg formation and higher pregnancy rates. We developed a
      prospective, linear and comparative study to aim the ovum/embryo development
      using urinary and recombinant FSH. A total of 100 patients were included in the
      study, 56 patients received rFSH (group I) and 44 hMG (group II). There were not
      differences in age, weight and body mass index as well as ovarian reserve.
      However, patients who used urinary gonadotrophins required a higher number of
      ampoules [31.7 +/- 8.6 vs. 20.7 +/- 6.4 (p < 0.001)]. No differences in peak E2,
      day of hCG and endometrial thickness. Although, no differences in number of egg
      mature, the fertilization rate was higher in the recombinant group [5.9 +/- 3.7
      vs. 3.4 +/- 2.3 (p < 0.02)]. A higher number of embryo transfer were observed in
      the same group (3.4 +/- 1.7 vs. 1.9 +/- 2.2 (p < 0.004)]. The pregnancy rates
      were 34.3% and 29.6% for each group respectively.

PMID- 11599316
TI  - [Prevalence of sexually transmitted diseases and the use of the condom among sex
      workers].
AB  - OBJECTIVE: To determine the prevalence of sexually transmitted diseases (STD) and
      the use of condoms by sex workers, assisted in a health module. MATERIAL AND
      METHODS: A cross sectional study, was performed with prostitutes in
      Coatzacoalcos, Veracruz through a self-administered questionnaire in a period
      from January 3 to February 9, 2001. The questionnaire evaluated gynecology
      obstetric background, STD and the use of condoms. Clinical records and laboratory
      tests were evaluated for STD screening. RESULTS: A total number of 196 sex
      workers from 71 work places were evaluated. The average age was 29.5 +/- 3.3
      years. One hundred and eleven (57%) reported being single. 189 (96.4%) presented
      at least a case of vaginosis during the year 2000 and 148 (75.5%) were diagnosed
      having vulvovaginitis due to fungus. Syphilis was identified in 4 (2%) cases and
      (0.5%) acquired immune deficiency syndrome. 45 (23%) reported they always use a
      condom and 113 (58%) use condoms very often. CONCLUSIONS: There is a high
      prevalence of vulva and vagina disorders, as well as syphilis. High rates of sex
      workers use condoms.

PMID- 11599317
TI  - [Assessment of nociceptive suppression in laparoscopic postoperative status:
      prospective, randomized and comparative study with a control group].
AB  - In recent years endoscopic surgery has became a highly demanded procedure because
      it is an easy method for diagnosis and treatment in gynecological field. Post
      operative pain is considered as a condition in the morbidity status. The
      objective of this study was to evaluate the nociceptive suppression in
      laparoscopic surgery. A prospective randomized trial was performed in order to
      evaluate this condition. A total of 45 patients were included. Three groups were
      randomized using two different anesthetics applied in the cult-de-sac and uterine
      bladder union. Group A (n-15) received bupivacaine, group B (n = 15) ropivacaine
      and group C (control) saline solution was instilled. The pain was scored using
      the visual analog scale as same as blood pressure and heart rate in a 15 minute
      intervals in the recovery room. For study design there were no differences in
      age, weight, height and body mass index (EMI). The surgical and anesthetic times
      were similar among groups. However there were significant differences when pain
      was evaluated. For a less toxic effects and good preventive analgesia we
      recommend to use ropivacaine in the postoperative status.

PMID- 11599318
TI  - [Frequency and etiology of azoospermia in the study of infertile couples].
AB  - One out of ten couples seek some kind of treatment for infertility of which males
      are infertile between 30-50%. Azoospermia has been reported in the range of 10 to
      20% of cases. MATERIAL AND METHODS: We reviewed 331 cases seen at the clinic of
      Reproductive Biology of the Hospital Juarez de Mexico, SSA, from January 1993
      through February 2000. 66 patients were found with azoospermia (19.93%). Studies
      performed were: seminogram, testicular and transrectal ultrasonography,
      cariotype, deferentovesiculography and testicular biopsy. Radioimmunoassay of
      gonadotropins (FSH, LH) and testosterone was also practiced. RESULTS: Twelve
      patients (18.18%) were excluded either for desertion or incompletion of studies.
      The etiology of azoospermia of remainder 54 cases was: secretory (85.19%) of
      which 41.3% was idiopathic, 10.9% had germ cells aplasia, 10.9% varichocele,
      10.9% Klinefelter syndrome. Secondary secreting azoospermia was found in two
      cases with Kallman's syndrome one patient had excretory and 7 obstructive
      azoospermia. CONCLUSIONS: Azoospermia was diagnosed in 19.93% (n = 54) with a
      mean age of 30 years. 85.19% had primary secretory azoospermia with FSH & LH
      hypergonadotropism in 85.8 and 56.4% respectively (p < 0.05). Obstructive
      azoospermia was seen in 12.96% and only one case (1.85%) presented excretory
      azoospermia.

PMID- 11599319
TI  - [Influence of intrafollicular factors at ovarian level during oocyte/embryo
      development].
AB  - There is series of factors associated to fertilization and embryo development
      events. Each factor has a role in the inter-relationship between various
      molecular events related to oocyte/embryo quality. Dynamic features associated to
      endocrine-paracrine environment are determinant to the role of each factor in
      ovaric follicullar development. Growth factors, vascular-endothelial growth
      factor, nitric oxide, leptin and others correlate in ovular maturity process.
      That is why growth factors, vascular-endothelial growth factor, nitric oxide,
      leptin and others can be expressed as embryo viability and implantation
      biomarkers.

PMID- 11599320
TI  - A patients' bill of rights for Canada?

PMID- 11599321
TI  - Prioritization for cataract surgery.

PMID- 11599322
TI  - Burgeoning career opportunities in radiation oncology.

PMID- 11599323
TI  - National stroke surveillance program needed in Canada.

PMID- 11599324
TI  - Update from the Canadian Stroke Consortium.

PMID- 11599325
TI  - If it looks like a cow and moos like a cow....

PMID- 11599326
TI  - Raloxifene and breast cancer.

PMID- 11599328
TI  - Income-based drug benefit policy: impact on receipt of inhaled corticosteroid
      prescriptions by Manitoba children with asthma.
AB  - BACKGROUND: Drug benefit policies are an important determinant of a population's
      use of prescription drugs. This study was undertaken to determine whether a
      change in a provincial drug benefit policy, from a fixed deductible and copayment
      system to an income-based deductible system, resulted in changes in receipt of
      prescriptions for inhaled corticosteroids by Manitoba children with asthma.
      METHODS: Using Manitoba's health care administrative databases, we identified a
      population-based cohort of 10,703 school-aged children who met our case
      definition for asthma treatment before and after the province's drug benefit
      policy was changed in April 1996. The effects of the program change on the
      probability of receiving a prescription for an inhaled corticosteroid and on the
      mean number of inhaled corticosteroid doses dispensed were compared between a
      group of children insured under other drug programs (the comparison group) and 2
      groups of children insured under the deductible program: those living in low
      income neighbourhoods and those living in higher-income neighbourhoods. All
      analyses were adjusted for a measure of asthma severity. RESULTS: For higher
      income children with severe asthma who were covered by the deductible program,
      the probability of receiving an inhaled corticosteroid prescription and the mean
      annual number of inhaled corticosteroid doses declined after the change to the
      drug policy. A trend toward a decrease in receipt of prescriptions was also
      observed for low-income children, but receipt of prescriptions was unaltered in
      the comparison group. Before the policy change, among children with severe
      asthma, the mean annual number of inhaled corticosteroid doses was lowest for low
      income children, and this pattern persisted after the change. Among children with
      mild to moderate asthma, those covered by the deductible program (both low income
      and higher income) were less likely to receive prescriptions for inhaled
      corticosteroids than those in the comparison group, and this difference was
      statistically significant for the higher-income children. INTERPRETATION: The
      change to an income-based drug benefit policy was associated with a decrease in
      the use of inhaled corticosteroids by higher-income children with severe asthma
      and did not improve use of these drugs by low-income children.

PMID- 11599327
TI  - Incidence of hepatitis C virus infection among injection drug users during an
      outbreak of HIV infection.
AB  - BACKGROUND: Beginning in 1994, Vancouver experienced an explosive outbreak of HIV
      infection among injection drug users (IDUs). The objectives of this study were to
      measure the prevalence and incidence of hepatitis C virus (HCV) infection in this
      context and to examine factors associated with HCV seroconversion among IDUs.
      METHODS: IDUs recruited through a study site and street outreach completed
      interviewer-administered questionnaires covering subjects' characteristics,
      behaviour, health status and service utilization and underwent serologic testing
      for HIV and HCV at baseline and semiannually thereafter. A Cox proportional
      hazards model was used to identify independent correlates of HCV seroconversion.
      RESULTS: As of Nov. 30, 1999, 1345 subjects had been recruited into the study
      cohort. The prevalence of anti-HCV antibodies was 81.6% (95% confidence interval
      [CI] 79.6% to 83.6%) at enrollment. Sixty-two HCV seroconversions occurred among
      155 IDUs who were initially HCV negative and who returned for follow-up, for an
      overall incidence density rate of 29.1 per 100 person-years (95% CI 22.3 to
      37.3). The HCV incidence remained above 16 per 100 person-years over 3 years of
      observation (December 1996 to November 1999), whereas HIV incidence declined from
      more than 19 to less than 5 per 100 person-years. Independent correlates of HCV
      seroconversion included female sex, cocaine use, injecting at least daily and
      frequent attendance at a needle exchange program. INTERPRETATION: Because of high
      transmissibility of HCV among those injecting frequently and using cocaine, the
      harm reduction initiatives deployed in Vancouver during the study period proved
      insufficient to eliminate hepatitis C transmission in this population.

PMID- 11599329
TI  - Arterial dissections following cervical manipulation: the chiropractic
      experience.

PMID- 11599330
TI  - Cervical manipulation and risk of stroke.

PMID- 11599331
TI  - Statins and the prevention of dementia.

PMID- 11599332
TI  - The modern scientific physician: 4. The useful property of a diagnostic.

PMID- 11599333
TI  - Clinical practice guidelines for the care and treatment of breast cancer: the
      management of ductal carcinoma in situ (summary of the 2001 update).

PMID- 11599335
TI  - Harm-reduction initiative provides alcohol to Ottawa's street alcoholics.

PMID- 11599336
TI  - Failure to study FPs' medical errors a mistake.

PMID- 11599337
TI  - Yellow fever vaccination: be sure the patient needs it.

PMID- 11599338
TI  - Antitubercular drugs (isoniazid, rifampin and pyrazinamide): hepatobiliary
      reactions.

PMID- 11599334
TI  - The pharmacology and toxicology of "ecstasy" (MDMA) and related drugs.
AB  - "Ecstasy" (MDMA) and related drugs are amphetamine derivatives that also have
      some of the pharmacological properties of mescaline. They have become popular
      with participants in "raves," because they enhance energy, endurance, sociability
      and sexual arousal. This vogue among teenagers and young adults, together with
      the widespread belief that "ecstasy" is a safe drug, has led to a thriving
      illicit traffic in it. But these drugs also have serious toxic effects, both
      acute and chronic, that resemble those previously seen with other amphetamines
      and are caused by an excess of the same sympathomimetic actions for which the
      drugs are valued by the users. Neurotoxicity to the serotonergic system in the
      brain can also cause permanent physical and psychiatric problems. A detailed
      review of the literature has revealed over 87 "ecstasy"-related fatalities,
      caused by hyperpyrexia, rhabdomyolysis, intravascular coagulopathy, hepatic
      necrosis, cardiac arrhythmias, cerebrovascular accidents, and drug-related
      accidents or suicide. The toxic or even fatal dose range overlaps the range of
      recreational dosage. The available evidence does not yet permit an accurate
      assessment of the size of the problem presented by the use of these drugs.

PMID- 11599339
TI  - Health professional advisories.

PMID- 11599340
TI  - Atypical antipsychotics: impaired glucose metabolism.

PMID- 11599341
TI  - [Morphological characteristics of fruits and seeds of Chinese Caesalpinia and its
      taxonomic significance].
AB  - OBJECTIVE: To set up a toxonomic approach to the morphological characteristics of
      fruits and seeds of Chinese Caesalpinia. METHOD: The ripe fruits collected in the
      field are dried in the shade, are surveyed and described and the fruit's and
      seed's morphological characteristics. RESULT: The interspecific differences of
      morphological characteristics among the fruits and seeds are obvious. The
      characteristics are stable. A key for their identification is given. CONCLUSION:
      The above approach can be used as the taxonomic criteria for species
      differentiation.

PMID- 11599342
TI  - [Determination of resibufogenin and cinobufagin in venenum Bufonis by HPLC].
AB  - OBJECTIVE: To establish a HPLC method to determine the contents of active
      constituents in Venenum Bufonis. METHOD: In determining the contents of
      resibufogenin and cinobufagin in the traditional Chinese medicine Venenum
      Bufonis, the mobile phase was acetonitrile-0.5% KH2PO4 solution(50:50)(pH
      adjusted with value phosphoric acid to 3.25 +/- 0.02). RESULT: The constituents
      thus determined have good linearity and separation. The average recovery of
      resibufogenin was 100.35%, RSD 1.86%; the average recovery of cinobufagin was
      100.38%, RSD 2.09%. CONCLUSION: The method was convenient, rapid, accurate and
      practicable.

PMID- 11599343
TI  - [Plantlet strengthening medium for Dendrobium candidum Wall. et Linde. of clonal
      propagation in vitro].
AB  - OBJECTIVE: To find a suitable medium for plantlet production of Dendrobium
      candidum in the period of strengthening plantlet. METHOD: The basic medium,
      natural aqueous extracts, density of banana aqueous extract and of plant hormones
      were tested. RESULTS AND CONCLUSION: The B5 or 1/2MS, added with 10% of banana
      aqueous extract and 2 mg/L NAA can be used as the best plantlet strengthening
      medium for Dendrobium candidum.

PMID- 11599344
TI  - [Effect of ginger-processing on the contents of guanosine in Pinelliae rhizoma
      (banxia)].
AB  - OBJECTIVE: To compare the guanosine contents in various products of Pinellia
      Rhizoma processed by different amounts of ginger and alum. METHOD: Using the
      technology of HPLC. RESULT: The guanosine contents in the two products of
      Pinellia Rhizoma processed in line with the pharmacopoeial method and orthogonal
      method respectively are very close to each other and change every little as
      compared with raw Pinellia Rhizoma. But the contents in the products of Pinelliae
      Rhizoma processed in other ways (digged in alum solution or in ginger Juice
      decocted with ginger juice, etc.) are much less than those of raw Pinellia
      Rhizoma. CONCLUSION: There are no obvious differences in guanosine contents
      between Pinellia Rhizoma processed by orthogonal technology and Pinellia Rhizoma
      processed by pharmacopoeial method. Processing technology has considerable
      influence on the water soluble components of Pinellia Phizoma.

PMID- 11599345
TI  - [Physicochemical changes in the process of preparing traditional Chinese drugs].
AB  - OBJECTIVE: Summarizing the physicochemical changes in the process of preparing
      traditional Chinese drugs and affording useful clues for the quality improvement
      of Chinese patent drugs. METHOD: Introducing the main physicochemical changes,
      such as precipitating reaction, solubility increasing, hydrolysis, and oxidation
      reduction etc., which occur in the process of extracting, separating,
      concentrating and drying. RESULT AND CONCLUSION: The research of physicochemical
      changes occurring in the process of preparation and the probe into their
      mechanism play an important role in perfecting the basic theories of Chinese
      pharmacy, promoting the development of compatibility theory of Chinese pharmacy
      and improving the technology design for preparing and controlling the quality of
      Chinese patent drugs.

PMID- 11599346
TI  - [Diterpenoid alkaloids from Aconitum bulleyanum Diels].
AB  - OBJECTIVE: To investigate the diterpenoid alkaloids from Aconitum bulleyanum.
      METHOD: Diterpenoid alkaloids were separated by solvent extraction and
      chromatography on silical gel, and their structures were determined by spectral
      analysis and chemical evidence. RESULT: Five diterpenoid alkaloids were
      elucidated as yunaconitine, crassicauline A, vilmorrianine C, lycoctonine and
      lappaconitine. CONCLUSION: All the compounds were isolated from this plant for
      the first time.

PMID- 11599347
TI  - [Preliminary studies on chemical constituents and pharmacological action of
      Eclipta prostrata L].
AB  - OBJECTIVE: To study the pharmacologically active components of Eclipta prostrata.
      METHOD: The components were extracted by alcohol and isolated by silica gel
      column and subjected to pharmacological screening. RESULT: Four compounds were
      isolated from E. prostrata, of which two were identified as stigmasterol and
      alpha-terthienyl. CONCLUSION: alpha-Terthienyl was isolated from the plant for
      the first time. The EtOAc part of alcoholic extraction exhibits significant
      hepatoprotective activity against carbon terachloride-induced liver injury in
      rats.

PMID- 11599348
TI  - [Chemical constituents of Cichorium intybus L].
AB  - OBJECTIVE: To investigate the chemical constituents of Cichorium intybus. METHOD:
      Constituents were separated by means of solvent extraction and chromatography on
      silical gel. The structures were established by spectral analysis and chemical
      evidence. RESULT: Seven compounds were isolated from the roots of C. intybus and
      four of them were identified as alpha-amyrin, taraxerone, baurenyl acetate and
      beta-sitosterol. CONCLUSION: All the four compounds were obtained from the plant
      for the first time.

PMID- 11599349
TI  - [Chemical constituents of Drosera peltata Smith var. lunata (Buch.-Ham.) C.B.
      clarke collected in Tibet].
AB  - OBJECTIVE: To investigate the chemical constituents of the whole plant of Drosera
      peltata var. lunata collected in Tibet. METHOD: Compounds were separated by means
      of pH gradient extraction and rechromatography on silica gel, and the structures
      were determined by spectral analysis and physicochemical evidence. RESULT: Five
      crystalline compounds were obtained and elucidated as plumbagin(1), droserone(2),
      hydroxydroserone(3), beta-sitosterol(4) and stigmasterol(5) respectively.
      CONCLUSION: Compound 3 and 5 were isolated from the plant for the first time.

PMID- 11599350
TI  - [Qualitative identification and quantitative determination of naringin in rhizoma
      Drynariae by TLC].
AB  - OBJECTIVE: To set up the method for the qualitative identification and
      quantitative determination of naringin in Rhizoma Drynariae. METHOD: TLC and TLC
      scanning. RESULT: Naringin in Drynariae fortunei was identified by TLC and its
      content was 0.73%. CONCLUSION: The TLC identification has been proved to be
      convenient, and the quantitative determination by TLC-scanning has been proved to
      be accurate, reliable and of good reproducibility, the recovery rate being
      100.48% and RSD 1.37% (n = 5).

PMID- 11599351
TI  - [Experimental studies on anti-inflammatory, antipyretic and diuretic effects of
      several species of tongcao and xiao-tongcao].
AB  - OBJECTIVE: To observe and compare the anti-inflammatory, antipyretic and diuretic
      effects of three kinds of Tongcao(Tongtuomu, Panyezhangyeshu and Luosan) and
      seven kinds of Xiao-tongcao(Ximashanjinjiehua, Xinanxiuqiu1. 2., Ditanghua,
      Suixuezhangcai, Qingjiaye and Zhongguo jinjiehua). METHOD: Decoctions prepared
      from the above kinds of Tongcao and Xiao-tongcao crude drugs were given to rats
      at dosages of 8 g/kg and 4 g/kg by ig. Pharmacological actions were observed by
      means of carrageenan-induced swelling paws, fever models induced by beer-yeast or
      carrageenan and metabolic cage method in rats. RESULT: All the experimental
      decoctions could inhibit carrageenan-induced swelling of rat paws in different
      degrees and exerted anti-pyretic effect on rat fever models induced by beer-yeast
      or carrageenan. Three kinds of Xiaotongcao(Ximashanjingjiehua, Xinanxiuqui2.,
      Zhongguojinjiehua) had obvious diuretic effect on rats. CONCLUSION: Decoctions of
      different species of Tongcao and Xiao-tongcao all have anti-inflammatory,
      antipyretic and diuretic effects, thus providing some pharmacologic basis for the
      efficacy assay, clinical application, species collation and quality study of
      Tongcao and Xiao-tongcao.

PMID- 11599352
TI  - [Inhibition of beta-amyloid precursor protein gene expression by haifengteng].
AB  - OBJECTIVE: To study the inhibition of beta-amyloid precursor protein(beta-APP)
      gene expression by Haifengteng. METHOD: Northern Blot analysis was used to
      investigate the level of beta-APP mRNA, and cell viability, LDH-release and
      colony formation assay were used to study the effect of Hairengteng of neurons.
      RESULT: Haifengteng inhibited the expression of beta-APP gene selectively without
      causing cell injuries. CONCLUSION: beta-APP is closely related to Alzheimer's
      disease. The findings in this study could be a basis for Haifengteng to have
      therapeutic potentials in treating Alzheimer's disease.

PMID- 11599353
TI  - [Clinical effect of tianma-cuzhi granules on senile vascular dementia].
AB  - OBJECTIVE: To assess the clinical efficacy of Tianma-cuzhi Granules (TMC) in
      treating senile vascular dementia(VaD) of the "sthenia of liver-yang" type.
      METHOD: TMC were given to thirty VaD patients three times a day of 0.5 g/bageach.
      The treatment course was one month and the patients finished two consecutive
      courses. RESULTS: TMC could markedly increase the mini-mental state examination
      (MMSE) and Hamilton depression scale(HDS) marks of VaD patients, and also
      contribute to improving certain indexes especially in abnormal cases. CONCLUSION:
      TMC have certain effects on senile VaD.

PMID- 11599354
TI  - [The powder X-ray diffraction analysis with Fourier spectrum of Chinese material
      medica Cortex Cinnamomi].
AB  - OBJECTIVE: To develop a method for the identification of Chinese medicinal
      materials in diffraction space. METHOD: Using powder X-ray diffraction analysis
      to obtain the Fourier spectrum of 10 samples of Cortex Cinnamomi. RESULTS: The
      analysis shows that each of the 10 samples has its own Fourier pattern topology
      and characteristic peaks which are connected with its chemical composition.
      CONCLUSION: Cortex Cinnamomi can be identified successfully according to its
      topology and characteristic peaks.

PMID- 11599355
TI  - [Determination of organochlorine pesticide residues in herba Asari by GC].
AB  - OBJECTIVE: To provide a theoretical guide for the production and application of
      Herba Asari. METHOD: A GC method for multiresidue analysis was used. RESULT:
      Fifteen samples of Herba Asari were detected with the method for the first time.
      The contents of organochlorine pesticide residues in most of the samples were
      under the Chinese national limits for grains and green vegetables (GB 2707-2763
      81). The other samples were polluted seriously. CONCLUSION: Some suggestions have
      been put forward to help keep down pesticide residue pollution in Chinese herbal
      medicines.

PMID- 11599356
TI  - [Production of allochtonic formations in callus cells of Salvia miltiorrhiza
      Bge].
AB  - OBJECTIVE: To study the effect of hormones content in the medium on of
      allochtonic formations in the callus from Salvia miltiorrhiza. METHOD: Study the
      development of allochtonic formations in the callus from explants of Salvia
      miltiorrhiza cultured on hormones of different content ratios in the medium.
      RESULT AND CONCLUSION: 2,4-D inhibits the production of water-soluble active
      principles and KT promotes the production of total tanshinone.

PMID- 11599357
TI  - [Metabolism in Arctium lappa L. at the primary stage of germination].
AB  - OBJECTIVE: To investigate the metabolic changes of the seeds at the primary stage
      of germination in Arctium lappa. METHOD: By means of electrophoresis the changes
      of peroxidases and soluble proteins were assayed at the primary stage of
      germination. RESULTS: The color of some original bands was enhanced, some
      original bands disappeared, and some new bands were detected in peroxidase
      patterns during the germinating process. The color changes were the main
      expression in soluble protein patterns. The bands of soluble proteins changed
      most obviously at 96 h and 120 h after germination. CONCLUSION: It follows that
      the metabolic process in the seeds of Arctium lappa at the stage of germination
      is complex and 96 h and 120 h after germination are the key times of metabolism.

PMID- 11599358
TI  - [Analysis of essential oils in prepared Chinese Angelica].
AB  - OBJECTIVE: Through chemical analysis of the essential oils obtained from prepared
      Chinese study Angelica to provide a scientific evidence for compatibility study
      of Siwu decoction. METHOD: Capillary GC-MS. RESULTS: In the essential oils of the
      head of Angelica 88 peaks have been detected and 42 of them (51.34% of the oils)
      have been identified; while in those of the whole Angelica 94 peaks have been
      detected and 54 of them (90.86% of the oils) have been identified. CONCLUSION:
      Constituents in the essential oils obtained from prepared Chinese Angelica have
      been identified for the first time.

PMID- 11599359
TI  - [Application and characteristics of macroreticular resin in purification study of
      different effective ingredients in Chinese medicines].
AB  - OBJECTIVE: To evaluate the possibility of applying macroreticular resin to the
      purification of different effective ingredients in Chinese medicines and study
      its working characteristics. METHOD: Four samples (water extracts of four single
      Chinese medicinal materials) containing alkaloids, anthraquinones, water soluble
      phenols and inorganic salts were employed. RESULT: LD605 resin is able to adsorb
      different effective ingredients except inorganic salts. CONCLUSION: Purification
      of Chinese compound prescriptions can be achieved by means of macroreticular
      resin.

PMID- 11599361
TI  - [Constituents in petroleum ether and ethyl acetate extract fractions of Dracaena
      cochinensis (Lour.) S.C. Chen].
AB  - OBJECTIVE: To study the chemical constituents of Dracaena cochinensis. METHODS:
      Compounds were separated by solvent extraction, column chromatography, TLC and
      HPLC, and their structures were determined by spectral analysis. RESULTS: Ten
      compounds were isolated from the petroleum ether and ethyl acetate fractions of
      D. cochinensis and identified as n-heptacosane, lophenol, docosanyl ferulate,
      tetracosanyl ferulate, hexacosanyl ferulate, octacosanyl ferulate, pterostilbene,
      dioctyl phthalate, butyl isobutyl phthalate and 4'-methoxy-3',7-dihydroxy
      flavone. CONCLUSION: All the compounds were isolated from this plant for the
      first time.

PMID- 11599360
TI  - [Studies on flavonoids from Fenugreek (Trigonella foenumgraecum L.)].
AB  - OBJECTIVE: To study the flavonoids in fenugreek (Trigonella foenumgraecum)
      produced in China. METHOD: The flavonoids were isolated with silica gel,
      polyamide and Sephadex LH-20 chromatography, and their structures were identified
      by physical, chemical properties and spectral analysis. RESULT: Five flavonoid
      compounds were isolated from fenugreek seeds and identified as vitexin, tricin,
      naringenin, quercetin and tricin-7-O-beta-D-glucopyranoside. CONCLUSION: Three
      flavonoids, tricin, naringenin and tricin-7-O-beta-D-glucopyranoside, were
      isolated from fenugreek as well as from the plants of Trigonella for the first
      time.

PMID- 11599362
TI  - [Chemical research on stilbenes from Veratrum macckii Reg].
AB  - OBJECTIVE: To study the components in rhizome of Veratrum macckii. METHODS:
      Column chromatography and preparative thin layer chromatography with silica gel
      were employed for the isolation and purification of constituents. The structures
      were elucidated by IR, MS and 1H-NMR analysis. RESULTS: Two compounds were
      obtained and elucidated as resveratrol and 2,3',4,5'-tetrahydroxystilbene.
      CONCLUSION: The two compounds were separated from V. macckii for the first time.

PMID- 11599363
TI  - [Chemical constituents of Bufo Siccus].
AB  - OBJECTIVE: To study the chemical constituents of Bufo Siccus. METHOD: Based on
      silica column chromatography six compounds were obtained from the alcoholic
      extract of Bufo Siccus and identified by physico-chemical and spectroscopic
      analyses. RESULT: The compounds were identified as cholesterol, beta-sitosterol,
      resibufogenin, cinobufagin, bufalin and gamabufotalin. CONCLUSION: Studies on the
      chemical constituents of Bufo Siccus were reported for the first time.

PMID- 11599364
TI  - [Effects of the leaf of Ginkgo biloba L. extract on blood rheology in animals].
AB  - OBJECTIVE: To observe the effects of the leaf of Ginkgo biloba extract(GBE) on
      viscosity and elasticity, coagulation of blood and aggregation of blood
      platelets. METHOD: The viscosity and elasticity of the whole blood in rats was
      determined using an in vitro method. The half inhibitory concentration of the
      drug inhibiting rabbit platelet aggregation was also determined using ADP as an
      inducer. The blood coagulation in mice was recorded with a coagulation analyser
      after GBE was administered by vein injection. RESULT: GBE significantly
      lengthened the recalcium time, lowered the increase ratios of viscosity and
      elasticity, and reduced the maximum viscosity and elasticity. At doses of 100 and
      200 mg/kg administrated by vein injection GBE lengthened the coagulation time,
      reduced the fibriogenesis and clot retraction ratio significantly in mice. GBE
      can also inhibit rabbit platelet aggregation induced by ADP and promote the
      disband of the aggregated platelets. CONCLUSION: GBE is helpful in reducing
      viscosity and elasticity of the whole blood, slowing blood coagulation and
      inhibiting platelet aggregation.

PMID- 11599365
TI  - [Effect of turmeric volatile oil on the respiratory tract].
AB  - OBJECTIVE: Researching the effect of turmeric volatile oil on functions of the
      respiratory tract. METHOD: The action of turmeric volatile oil on sputum
      removing, cough and asthma relieving was observed by vapour inhaling. RESULT: The
      volatile oil is significantly active in removing sputum, relieving cough and
      preventing asthma. CONCLUSION: Turmeric volatile oil may be an efficacious drug
      for the treatment of respiratory diseases.

PMID- 11599366
TI  - [Protective effect of hyperin on cerebral infarction in rats].
AB  - OBJECTIVE: To study the protective effect of hyperin (Hyp) on cerebral
      infarction. METHOD: The cerebral infarction in rats was made by ligating the
      right common carotid artery and the right middle cerebral artery. The infarction
      weight was determined by NBT stain. The cerebral cortex was taken to measure
      nitric oxide (NO) and malondialdehyde (MDA). The cerebral blood flow(CBF) was
      measured with H2 clearance method. RESULT: Hyp 6.25, 12.5, 25 mg.kg-1 markedly
      improved the abnormal nervous symptoms, and 12.5, 25 mg.kg-1 Hyp significantly
      reduced the infarction weight and inhibited the increase of MDA and NO in the
      cerebral cortex. Hyp(25, 12.5 mg.kg-1) could increase the CBF of the cerebral
      cortex. CONCLUSION: Hyp has a protective effect on cerebral infarction via
      attenuating lipid peroxidation and NO.

PMID- 11599367
TI  - [Influence of huanglian used in combination with huangqin and gancao on the
      erythrocytic osmotic fragilitas of experimental glucose-6-phosphate dehydrogenase
      deficiency in rats].
AB  - OBJECTIVE: To study the influence of common combination of Huanglian(Coptis
      chinensis) on the erythrocytic osmotic fragilitas of glucose-6-phosphate
      dehydrogenase(G6PD) deficiency in rats. METHOD: Various decoctions with Huanglian
      mixed with Huangqin (Scutellaria baicalensis) and Gancao(Glycyrrhiza uralensis)
      were orally administered to the G6PD deficiency rat model, and the erythrocytic
      osmotic fragilitas was measured. RESULT: The erythrocytic osmotic fragilitas
      after the combined use of Huanglian appears lower than (or equal to) that of
      Huanglian used alone(or even not used). The fragilitas lowers depending largely
      on the medicine in combination, dosage and proportion. CONCLUSION: Proper use of
      Huanglian in combination with Huangqin and Gancao is of some significance in
      lowering the erythrocytic osmotic fragilitas of G6PD deficiency in rats.

PMID- 11599368
TI  - [Observation on the surface characteristics of the leaves of Dysosma and its
      related genus by scanning electronic microscope].
AB  - OBJECTIVE: To observe the surface characteristics of leaves of Dysosma and its
      related genus by SEM for identification. METHOD: Leaf surface characteristics of
      seven species of Dysosma and tow species of its related genus were observed by
      scanning electronic microscopic method. RESULT: The leaf surface characteristics
      of upper epidermis and lower epidermis of the nine plants are different from each
      other. A key and illustrations were listed. CONCLUSION: The leaf surface
      characteristics observed by SEM can be used for identification of Dysosma and its
      related plants.

PMID- 11599369
TI  - [Observation on trachea inner walls of six species of Sect. Stenophora by
      scanning electronic microscope].
AB  - OBJECTIVE: To probe and identify the ultramicro characteristics of trachea inner
      walls(TIW) of six species of Sect. Stenophora, i.e., Rhizoma Dioscoreae
      Spongiosae, Rhizoma Dioscoreae Hypoglaucae, Rhizoma Dioscoreae Futschauensis,
      Rhizoma Dioscoreae Gracillimae, Rhizoma Dioscoreae Tokoro and Rhizoma Dioscoreae
      Zingiberensis, by scanning electron microscope (SEM). METHOD: The vertical
      microscopical sections are stuck on the platform of species and metal plated. TIW
      were observed and photographed by SEM. RESULT: The ultramicro characteristics of
      TIW, i.e., the smoothnesss of TIW, the existence of separation bands, the
      density, arrangement types, shapes and sizes of pits, etc., can be seen clearly
      under SEM. Further, there exist differences in the ultramicro characteristics of
      each species. CONCLUSION: The above six species of crude drugs can be identified
      according to their ultramicro characteristics of TIW. SEM can be used to study
      the ultramicro characteristics of crude drug rhizomas thus creating a new area
      for identifying crude drugs.

PMID- 11599371
TI  - [On the best time for harvesting Dendrobium candidum Wall. ex Lindl].
AB  - OBJECTIVE: To explore the theory on the best time for harvesting Dendrobium
      candidum so that the production of the herb can be directed more effectively.
      METHOD: Based on a component analysis in combination with mathematical
      calculation, a synthetical appraisal on the yield, contents of effective
      components and efficacy of D. candidum in different growing periods has been
      made, and different appraisal indexes and synthetical harvesting indexes have
      been worked out. RESULT: The harvesting indexes from the first year to the fourth
      year are as follows: 5.69, 9.54, 17.9, 22.2 (curing throat and eye diseases);
      11.2, 14.6, 21.6, 17.6(strengthening immunity); 8.44, 12.1, 19.7, 19.9(the above
      mentioned indexes and yield factor considered together). CONCLUSION: The best
      time for harvesting D. candidum is in the fourth year for curing throat and eye
      diseases; in the third or first year for strengthening immunity; and in autumn of
      the third year if the above-mentioned indexes and yield factor are to be
      considered together.

PMID- 11599370
TI  - [Determination of oil contents and fatty acids in seeds of Torreya Arn. in
      China].
AB  - OBJECTIVE: To analyze the oil contents and fatty acid composition in the seeds of
      Torrreya in China. METHOD: The contents and composition were determined by
      gravimetric analysis and GC respectively. RESULT: The oil contents in the seeds
      were 42.67%-54.39%. Among the fatty acids, linoleic acid and oleic acid were
      dominant. The unsaturated fatty acids accounted for 76.1%-82.0% of the whole
      fatty acids, and the major saturated fatty acids were behenic acid and palmitic
      acid. CONCLUSION: The oil in the seeds of Torreya is of high-quality, and the
      higher contents of bdhenic acid are characteristic for the oil. The development
      and utilization values of the seed oil in Torreya are evaluated.

PMID- 11599373
TI  - [Investigation on computative spectrophotometry employed in the assay of peaonol
      in cortex moutan].
AB  - OBJECTIVE: To investigate the easibility of employed computative
      spectrophotometry in the assay of traditional Chinese medicines. METHOD: Make
      contents of peaonol in 10 samples of Cortex Moutan were determined by three
      wavelength spectrophotometry and dual wavelength K-ratio spectrophotometry, and
      then compared with the method in Chinese Pharmacopeia. RESULT: The differences of
      the UV spectrum of different lots of samples bring about relative error.
      sometimes up to 10%-30% for computative spectrophotometry. CONCLUSION:
      Computative spectrophotometry should be used carefully in assaying traditional
      Chinese medicines.

PMID- 11599372
TI  - [Chemical constituents of Rheum wittrochii Lundstr(II)].
AB  - OBJECTIVE: To study the chemical constituents in the root of Rheum wittrochii.
      METHOD: Chromatography and spectroscopic analysis to isolate and elucidate the
      chemical constituents in the plant. RESULT: Six compounds, namely 3, 5-dihydroxy
      4'-methoxystilbene; 3, 5, 4'-tridroxystilbene; piceatannol; desoxyrhaponticin;
      piceatannol-4'-O-beta-D-glucopyranoside; 2, 5-dimethyl-7-hydroxychromone, have
      been isolated from ethyl ether and ethyl acetate fractions. CONCLUSION: These
      compounds were isolated from the title plant for the first time.

PMID- 11599374
TI  - [Effects of ligustrazine on myocardium and coronary artery].
AB  - OBJECTIVE: To study the effects of ligustrazine on mechanical electricity in
      guinea pig ventricular papillary muscles and on contraction of pig coronary
      artery. METHOD: Standard glass microelectrode technology; electrophysiological
      method; and blood vessel perfusion were used. RESULT: 1. ligustrazine(3-100
      mumol/L) suppressed the action potential duration (APD) and the force of
      contraction (FC) of the fast action potentials (FAP), as well as the action
      potential amplitude (APA), APD, FC and the maximal upstroke velocity(Vmax) of the
      slow action potentials (SAP). 2. ligustrazine (3.0 mmol/L) induced SAP and
      contraction, but failed in beta-adrenoreceptor blocked muscles. Elevation
      of[Ca2+]o increased the action potential amplitude (APA). 3. ligustrazine(10(-5)
      5 x 10(-3) mol/L) decreased the contractile response to high KCl in pig coronary
      artery. CONCLUSION: Ligustrazine might affect the inward current of myocardial
      cells through beta-adrenoreceptor, and the diastolizing effect of ligustrazine on
      coronary artery might have nothing to do with the exciting beta-adrenoreceptor.

PMID- 11599375
TI  - [Observation of antiarrhythmic effects of Cinnamomum migao H. W. Li on
      experimental arrhythmia].
AB  - OBJECTIVE: To investigate the effects of Cinnamomum migao on experimental
      arrhythmia. METHOD: Arrhythmic models of mice, rabbits, guinea pigs and rats were
      built using chloroform(Chl), adrenalin(Adr), strophanthin-K (Spt-K) and barium
      chloride (BaCl2). The affected animals were divided randomly into three groups:
      control group, Cinnamomum migao (CV-3) group and mexiletine (MXL) group, so as to
      observe and compare the antiarrhythmic effects. RESULT: CV-3 could reduce the
      incidence of ventricular fibrillation caused by ch1 in mice and the ventricular
      tachycardia induced by Adr in rabbits, delay the onset time of this arrhythmia,
      increase the arrhythmic doses of Spt-K in guinea pigs, reduce the incidence of
      some arrhythmia caused by BaCl2 in rats and slow down their heart rate.
      CONCLUSION: CV-3 has obvious antiarrhythmic effects on experimental arrhythmia.
      The mechanism of these effects is probably related to the arrest of the intraflow
      of Na+, Ca2+ in the cardiac cells and the depression of their cardiac
      autoarrhythmicity and conductivity.

PMID- 11599376
TI  - [Experimental study of dahuang zhechong pills in the treatment of immunological
      liver fibrosis in rats].
AB  - OBJECTIVE: To study the effect of DHZC on liver fibrosis. METHOD: Immuno-injured
      fibrosis in rats was induced by bovine serum albumin and DHZC was given during
      and after the model production respectively. Hepatic collagen contents, pathology
      of liver and serum hyaluronic acid were measured. Colchicine was used as control.
      RESULT: It shows that the liver fibrosis rates of the DHZC treated group during
      and after the model production were 72.7% and 71.2% respectively, while those of
      the untreated and colchicine group were 92.3%-100%. Compared with the untreated
      group, there was a remarkable decrease of hepatic collagen contents in the DHZC
      treated rats. CONCLUSION: DHZC have thus been proved helpful in reversing liver
      fibrosis to some extent.

PMID- 11599377
TI  - [Progress in the immunopharmacological study of yupingfeng powder].

PMID- 11599378
TI  - [Calcium oxalate crystals in several kinds of Cinnamon bark].
AB  - OBJECTIVE: To probe into the morphology and distribution characteristics of
      calcium oxalate crystals in several kinds of Cinnamon bark. METHOD: Forty samples
      of ten different species of Cinamomi Cortex were examined, and the inter-cellular
      calcium oxalate crystals in the phloem rays were observed by optical microscope
      and scanning electron microscope. RESULT: It was found that for samples of the
      same botanical origin, there is little variation in the crystal morphology
      following certain regularity. The amount, size and ultra-micromorphologic
      characteristics are influenced by various factors. CONCLUSION: The pattern of
      morphology and distribution of calcium oxalate crystals may well be an index for
      identification of the crude drug of Cinnamon bark.

PMID- 11599379
TI  - [Determination of oleanolic acid and total saponins in Aralia L].
AB  - OBJECTIVE: To search for higher contents of olenolic acid and saponins in Aralia
      for medicinal use. METHOD: A HPLC method was developed for the determination of
      olenolic acid in Aralia. An YWG C-18 column was used and the mobile phase was
      methanol-water(90:10). The detection wavelength was UV 210 nm. The total saponins
      were determined by colorimetry. RESULT: Olenolic acid in root or stems of 13
      species and total saponins in whole roots and root barks of 14 species of Aralia
      were determined. The contents of olenolic acid and total saponins in woody Aralia
      were higher than those in herbaceous. CONCLUSION: The contents of olenolic acid
      in A. decaisneana, A. elata, A. chinocaulis, A. chinensis and A. chinensis var.
      dasyphylloides are higher than those in other species. Furthermore, A.
      decaisneana and A. elata are rich in wild resources and thus of importance to the
      development and utilization of wild plants containing olenolic acid.

PMID- 11599380
TI  - [Analysis of isoenzymes in six kinds of caulis drug by means of polyacrylamide
      gel slab electrophoresis].
AB  - OBJECTIVE: To probe into the possibility of application of electrophoresis in the
      identification of caulis drugs. METHOD: The isoenzymes of peroxidase, esterase
      and amylase in six kinds of caulis drug with similar characteristics were
      analyzed by means of polyacrylamide gel slab electrophoresis. RESULT: The bands
      of isoenzymogram of peroxidase are the clearest of all, and band number and
      mobility rates of the six drugs differ from one another, showing a remarkable
      interspecific distinction. CONCLUSION: Electrophoresis of isoenzymes of
      peroxidase can be employed as one of the effective means in differentiating
      caulis drugs.

PMID- 11599381
TI  - [Research on the propagation of Trillium tsehonoskii M. in vitro].
AB  - OBJECTIVE: To develop a technique of propagating. Trillium tsehonoskii in vitro
      as new way to conserve and utilize this special medicinal plant. METHOD: Segments
      from different organs of the plant sampled at different growth stages were
      cultured on MS medium supplemented with various combinations of BA, IAA, NAA and
      zeatin in a set of concentrations. RESULT: The effects of the induction of callus
      and differentiation of sprouts were investigated, showing that BA and IAA favored
      the formation of callus. The stock segments taken in the period of rapid growth
      of the plant were suitable for tissue culture. The induction rate of callus from
      the stock segments was as high as 21.9% and easy to differentiate micro-stock and
      plantlets, which may result from an activate function of stock cambium to enhance
      cell division during the stage of sprouting to rapid growth. CONCLUSION: The
      tissue culture method is a practicable and potential biotechnological way to
      multiply Trillium tsehonoskii plants. One key point to establish an in vitro
      system is to further improve the plantlet differentiation rate of the callus
      induced.

PMID- 11599383
TI  - [Effect of scald processing on the content of recibufogenin in Pellis sicci
      Bufonis].
AB  - OBJECTIVE: To investigate the effect of scald processing on the content of
      recibufogenin in Pellis Sicci Bufonis. METHOD: Samples were analyzed by high
      performance liquid chromatography. RESULT: The content of recibufogenin in the
      scald processed product was 25.7% higher than that in the unprocessed one. The
      average recovery was 98.34% and RSD 1.28%. CONCLUSION: The results indicate that
      the content of recibufogenin in scald processed Pellis Sicci Bufonis is higher
      than that in the unprocessed drug.

PMID- 11599382
TI  - [Determination of ferulic acid and peoniflorin in siwu decoction prepared by
      different methods of yellow rice wine].
AB  - OBJECTIVE: To compare the influence of different methods with YRW (yellow rice
      wine) on the composition of Siwu decoction. METHOD: TCL-SM was used to determine
      the ferulic acid, paeoniflorin and matters dissolved in ether in Siwu decoction.
      RESULT: The Siwu decoction with YRW preparation has the highest contents, while
      the Siwu decoction containing Chinese Angelica root and Rehmammia root prepared
      with YRW has the lowest contents. CONCLUSION: The Siwu decoction prepared with
      YRW or added with YRW is more helpful for ferulic acid and paeoniflorin to be
      dissolved out than the Siwu decoction containing Chinese Angelica root and
      Rehmannia root prepared with YRW.

PMID- 11599384
TI  - [Research and application of far-infrared rays to drying Chinese medicinal herbs
      in small pieces].
AB  - OBJECTIVE: To introduce a far-infrared ray dryings device. METHOD: The research
      background, work tenets, structure, function, technical parameters and tentative
      application of the device were reported. Chinese medicinal herbs in small pieces
      which contain volatile oils were dried by far-infrared rays and airing. The two
      drying methods were compared. RESULT AND CONCLUSION: Not degrading the quality of
      medicinal herbs in small pieces, the device can be used to dry various kinds of
      medicinal herb pieces and thus deserves popularization.

PMID- 11599385
TI  - [Compatible leaching effect of Concha Ostreae and some commonly-used Chinese
      medicinal materials].
AB  - OBJECTIVE: Based on a study of Concha Ostreae, to provide some reference for the
      rational approach to leaching mineral drugs. METHOD: Taking the change rates of
      compatible leaching and value of A as targets, the compatible leaching effect of
      Concha Ostreae with Radix et Rhizoma Rhei Praeparata, Radix Scutellariae, Pollen
      Typhae and Fructus Aurantii lmmaturus was studied. RESULT: If Concha Ostreae and
      the above cited medicinal herbs are decocted together, the yield of extract may
      be reduced to a certain extent, but the target composition of Radix et Rhizoma
      Rhei Praeparata and Fructus Aurantii lmmaturus remains intact, only the content
      of Radix Scutellariae baicalin may be influenced. CONCLUSION: The relationship of
      technology with preparation must be taken into consideration when making choice
      of the proper way to leach Concha Ostreae.

PMID- 11599386
TI  - [Isolation and identification of Triterpenoid compounds in the fruits of
      Chaenomeles lagenaria (Loisel.) Koidz].
AB  - OBJECTIVE: The fruit of Chaenomeles lagenaria is a commonly used drug in Chinese
      traditional medicine. It is especially effective on rheumatism. The current work
      is to find out the chemical basis of its pharmacological activity. METHOD: All
      compounds were extracted with organic solvents and separated by silica gel column
      or thin layer chromatography, and then purified by recrystalization. The
      structures were elucidated on the basis of chemical reactions and spectral data
      analysis. RESULT: In addition to the compounds reported in our previous work,
      three triterpenoid compounds were separated and identified as 3-O-acetyl ursolic
      acid, 3-O-acetyl pomolic acid and betulinic acid respectively. CONCLUSION: It is
      obvious that triterpenoid compounds are dominant among the chemical constituents
      of C. lagenaria. But it is still to be clarified whether they are the chemical
      basis of the drug's pharmacological activity.

PMID- 11599388
TI  - [Studies on tannins from Tripterygium hypoglaucum (levl.) hutch].
AB  - OBJECTIVE: To study the tannins from Tripterygium hypoglaucum. METHOD: Compounds
      were isolated by column chromatography and elucidated on the basis of
      spectroscopic analysis and comparison of references. RESULT: The compounds
      obtained were determined as (+)catechin, (-)epigallocatechin, procyanidin B-3,
      procyanidin B-4 and gallocatechin-(4 alpha-->8) epicatechin. CONCLUSION: All the
      compounds were obtained from this plant for the first time.

PMID- 11599387
TI  - [Chemical constituents of Quercus mongolica Fisch].
AB  - OBJECTIVE: To study the chemical constituents of the leaves of Quercus mongolica.
      METHOD: Using techniques of silical gel column chromatography and HNMR, 13CNMR.
      RESULT: Four compounds were isolated and identified as friedelin, glutinol, lupeo
      and beta-sitosterol respectively. CONCLUSION: All the compounds were isolated
      from this plant for the first time.

PMID- 11599389
TI  - [Water-soluble ginsenosides in American ginseng].
AB  - OBJECTIVE: To have further comprehension of American Ginseng on the basis of its
      water-soluble components. METHOD: The water suspension of 80% methanol extract of
      American Ginseng was sequentially extracted with ethyl ether and n-butyl alcohol.
      The saccharides in the water-soluble portion were removed by macro-reticular
      resin column, and three compounds were obtained by silica-gel column
      chromatography. Their structures were confirmed on the basis of spectral
      analysis(IR, NMR, MALDI-MS) melting points and optical degrees. RESULT: Three
      compounds were identified as malonyl ginsenosides Rb1, ginsenoside Rb1 and Re
      respectively. Among them Rb1 and Re are known, while malonyl ginsenoside Rb1 was
      isolated from American Ginseng for the first time. Its structure was elucidated
      as (3 beta, 12 beta)-20-[(-6-O-beta-D- glucopyranosyl-beta-D-glucopyranosyl)oxy]
      12-hydroxylammar-24-en-3-yl-O- [6-O-(carboxyacetyl)-beta-D-glucopyranosyl)]-beta
      D-glucopyranoside. CONCLUSION: Water-soluble ginsenosides were isolated from the
      water-soluble extract of American Ginseng suggesting that malonyl ginsenosides
      exist both in American Ginseng and Ginseng.

PMID- 11599390
TI  - [Chemical constituents of Conyza blinii Levl].
AB  - OBJECTIVE: To study the chemical constituents in the air-dried part of Conyza
      blinii. METHOD: The constituent isolation was done by solvent-extraction together
      with column chromatography. Several methods, such as IR, 1HNMR, 13CNMR and MS,
      were used to determine the structures of the isolated constituents. RESULT: Three
      compounds were isolated from the air-dried part of Conyza blinii and identified
      as friedelinol, n-triacontanol and daucosterol on the basis of physical and
      chemical properties and spectroscopic analysis. CONCLUSION: These compounds have
      not been discovered previously in this plant.

PMID- 11599391
TI  - [Anti-oxidative action of the glycosides of Cistanche in the tissue of mice].
AB  - OBJECTIVE: To study the anti-oxidative action of GCS in the tissues of mice.
      METHOD: Contents of superoxide dismutase (SOD), malondialdehyde (MDA) and
      lipofuscin in the heart, liver, brain and kidney of mice were measured, using
      pyrogallic acid, thiobarbi turic acid(TBA) and fluorescent technique
      respectively. RESULT: It was found that the GCS (125 mg/kg, 250 mg/kg) had a
      significantly higher SOD activity and lower MDA contents in brain and kidney than
      that in control group. GCS(250 mg/kg) enhanced SOD activity in the heart and
      liver, declined contents of MDA and lipofuscin in all tissues. CONCLUSION: The
      results suggest that GCS could increase the antioxidative action in vivo
      significantly and prevent lipoperoxidative damages in tissues.

PMID- 11599392
TI  - [Mechanism of Canscora lucidissima xanthones against arrhythmia induced by
      myocardial ischemia-reperfusion in rats].
AB  - OBJECTIVE: To study the protective effect of 1,8-dihydroxy-3,5- dimethoxyxanthone
      (Xan-I) 1-hydroxy-5-dimethoxyxanthone(Xam-II) and 1-hydroxy-3,7,8
      trimethoxyanthone (Xan-III) on arrhythmia induced by myocardial ischemia
      reperfusion injury and their mechanism. METHOD: A rat model was used. The
      experimental result shows that. RESULT: An intravenous injection of Xan-I, Xan-II
      and Xan-III 1 mg/kg given 3 min before left coronary artery ligation reduces
      significantly the incidence of ventricular arrhythmia and its duration,
      diminishes the release of glutamic oxaloacetic transaminase and lactate
      dehydrogenase, elevates the activity of superoxide dismutase and reduces the
      amount of malondialdehyde. The potency of the above effect among 3 Xans is Xan-I
      > Xan-III > Xan-II. CONCLUSION: It follows that the protective effect of Xans on
      myocardial ischemia reperfusion induced by arrhythmia might be associated with
      the reduction of myocardial lipid peroxidation and the enhancement of SOD
      activity, and the amount and site of-OH(hydroxy) and -OCH3 (methoxy) on the
      benzenoid structure may be related to the affinity of Xan.

PMID- 11599393
TI  - [Effect of guizhi fuling pills on the changes of Ca2+ and amino acids in rats
      with cerebral ischemia and reperfusion].
AB  - OBJECTIVE: To Probe the action of the Chinese traditional medicine Guizhi Fuling
      Pills on rats with cerebral ischemia and reirrigation. METHOD: The changes of
      Glu, Asp, Gly and GABA in serum and cerebral tissues were determined, and the
      degrees of Ca2+ and the cerebral ebema were analyzed. RESULT: The contents of
      Glu, Asp, Gly, GABA and Ca2+ in the pills treated group are different from those
      in the control. CONCLUSION: Guizhi Fuling Pills help alleviate ischemia-induced
      cerebral injuries.

PMID- 11599394
TI  - [Influence of huanglian and berberine on the erythrocytic osmotic fragilitas of
      experimental glucose-6-phosphate dehydrogenase deficiency in rats].
AB  - OBJECTIVE: To make clear the influence of Huanglian (Coptis chinensis) and
      berberine on the erythrocytic osmotic fragilitas of glucose-6-phosphate
      dehydrogenase(G6PD) deficiency in rats, so as to infer whether Huanglian and
      berberine have medicamentosus hemolysis effects. METHOD: Huanglian decoction and
      berberine solution are applied to the erythrocytes of G6PD deficiency in rats
      through external and oral administration and the erythrocytic osmotic fragilitas
      is measured. RESULT: Only at an excessively high dose can the medicines raise the
      erythrocytic osmotic fragilitas of G6PD deficiency in rats. Berberine and
      Huanglian have similar effects, but berberine is slightly weaker. CONCLUSION:
      Focus on the erythrocytic osmotic fragilitas, at a general dose, Huanglian can
      not cause hemolysis. Huanglian and berberine are of more safety to normal
      erythrocytes.

PMID- 11599395
TI  - [Advances in the study of feces Trogopterori].

PMID- 11599396
TI  - Consultation for photoaging skin.
AB  - Chemical peeling remains a valuable tool for the cosmetic surgeon to treat
      photoaging skin. Choices available include superficial, medium, and deep chemical
      peeling agents along with preparatory cosmoceutical agents to prep the skin and
      maintain rejuvenation. This article will prepare the cosmetic surgeon to include
      the latest agents in his practice and correctly choose which treatment is best
      for patients with individual problems of photoaging of the face and body, acne
      scars, and pigmentary problems. These modalities will be compared with other
      treatment modalities, such as laser and dermabrasion.

PMID- 11599397
TI  - Dermal peels.
AB  - Dermal chemical peeling is a very satisfying procedure for patients and
      physicians alike. Although not providing the ablation of deep wrinkles and scars
      that dermabrasion and laser procedures may accomplish, trichloroacetic acid peels
      usually result in few complications and rapid recovery. Patients can usually
      expect photographic improvement in their skin. The results are usually long
      lasting, and most patients do not need to repeat dermal peels for at least 2
      years. Of all resurfacing procedures, dermal peeling provides the best benefit-to
      risk ratio.

PMID- 11599398
TI  - Medium-depth chemical peels.
AB  - The combination medium-depth chemical peel (Jessner's solution +35% TCA) has been
      accepted as a safe, reliable, and effective method for the treatment of moderate
      photoaging skin. This article discusses the procedure in detail, including
      postoperative considerations.

PMID- 11599399
TI  - Complications of chemical resurfacing.
AB  - Complications of chemical resurfacing may occur even though a controlled chemical
      wound has been induced. The surgeon must be totally familiar with the types of
      peels and the management of postoperative wound care based on the skin type of
      the patient. A thorough understanding of the concepts involved will enable early
      treatment and avoidance of permanent sequelae, such as pigmentary dyschromias,
      infection, or scarring.

PMID- 11599400
TI  - Dermabrasion.
AB  - This article provides an overview of the resurfacing technique of dermabrasion.
      Preoperative consultation, perioperative medications, postoperative management,
      common complications, and reasonable outcome expectations are all described in
      detail. A description of proper technique, intraoperative equipment, and an
      approach to full-face procedures is also described.

PMID- 11599401
TI  - CO2 laser resurfacing.
AB  - The CO2 Laser offers a variety of unique features in resurfacing facial
      photodamage and acne scarring. These include hemostasis, efficient removal of the
      epidermis in a single pass, thermally induced tissue tightening, and safe,
      predictable tissue interaction. Knowledge of these mechanisms will result in the
      capability of using the CO2 laser effectively and safely whether the goal is
      superficial or deep treatment.

PMID- 11599402
TI  - Erbium:YAG cutaneous laser resurfacing.
AB  - The short-pulsed Er:YAG laser system is an excellent ablative tool for cutaneous
      resurfacing. This system is most efficacious for patients with milder cutaneous
      involvement, including mild photoinduced facial rhytides, mildly atrophic scars,
      and textural changes caused by fibrosis and dermatochalasis. The Er:YAG laser
      cannot achieve the same dramatic clinical and histologic improvements produced
      with the CO2 laser but does offer some distinct advantages that make it a
      valuable addition to the laser surgeon's armamentarium. The Er:YAG laser, because
      of its higher affinity for water-containing tissues, effects a much finer level
      of tissue ablation. Although erbium laser resurfacing results in decreased
      postoperative morbidity with a shorter recovery period, it cannot effect the same
      degree of improvement in photodamaged skin as can the CO2 laser. Excellent
      results, however, can be achieved with this laser, up to 50% or more overall
      clinical improvement, in patients with milder photodamage and scarring (Glogau
      classes I and II). In darker-skinned patients, the Er:YAG laser is often the
      preferred treatment modality. Continued research in the field has already led to
      the development of longer-pulsed Er:YAG lasers, which offer a compromise between
      the CO2 laser and the short-pulsed Er:YAG lasers in terms of clinical benefits
      while maintaining the safety profile of the traditional short-pulsed system. In
      addition, many surgeons now use a combination approach with the CO2 and Er:YAG
      lasers in an effort to maximize collagen contraction in certain areas and limit
      postoperative morbidity. As more research is conducted within the field of
      cutaneous resurfacing, newer systems will be developed in the continuing effort
      to create the ideal laser system--one which ameliorates the signs of photoaging
      without risk of major side effects or significant postoperative recovery.

PMID- 11599403
TI  - Treatment of leg veins with lasers and intense pulsed light. Preliminary
      considerations and a review of present technology.
AB  - Each laser system has different wavelengths, spot sizes, cooling mechanisms, and
      pulse durations. This article examines the advantages and disadvantages of
      different lasers with the proposition that, in the end, the best laser is the one
      that the practitioner can use best.

PMID- 11599404
TI  - Small-vessel sclerotherapy.
AB  - Small vessel telangiectasias are commonly seen in clinical dermatology. This
      article focuses on the evaluation of these patients and treatment. The types of
      sclerosing agents and the techniques of sclerotherapy are discussed in detail.

PMID- 11599405
TI  - Liposuction.
AB  - This is a basic overview of liposuction. Liposuction is the removal of fat using
      cannulas (tubes) inserted through tiny incisions into the adipose tissue. When
      done correctly, nice results can be safely achieved with a very easy procedure.

PMID- 11599406
TI  - Skin filling. Collagen and other injectables of the skin.
AB  - Minimally invasive soft tissue augmentation of the face with injectable
      substances has been performed for more than a century. During this period, many
      substances have been used to cosmetically improve soft-tissue defects and
      deficiencies. Some have lasted; most have not. These procedures have become
      increasingly important as more patients seek aesthetic improvement without major
      surgical procedures. This article reviews the current status of these materials
      and techniques.

PMID- 11599407
TI  - Dermal grafting.
AB  - At the 1999 American Academy of Dermatology symposium on soft-tissue
      augmentation, Dr. Arnold Klein mentioned 31 different [figure: see text] filler
      substances now available world-wide. Of these 31, 29 were either synthetic or
      modified, and only two (dermis and fat) were autologous material reimplanted
      without significant alteration. Dermal grafts have stood the test of time. Before
      skin surfacing is performed, one must fill up depressions not improved by the
      resurfacing technique. The dermatologist or plastic surgeon should seriously
      consider adding dermal grafting to his or her armamentarium. Patients will likely
      be grateful!

PMID- 11599408
TI  - Fat grafting.
AB  - Autologous adipose tissue has been used for tissue augmentation for over a
      century. The technique still remains controversial and some investigators have
      given up on fat transfer. The authors' objective is to improve the retention of
      the fat graft by using less traumatic methods to collect the fat, to concentrate
      it, and to reinject it to obtain more reliable augmentations for the cosmetic
      improvement of tissue defects. The fat is collected from the donor site following
      tumescent infiltration of the tissue. A Mercedes cannulae is used with a vented
      syringe. The fat is centrifuged to remove excess tumescent fluid or demineralized
      bone powder is added if a more dramatic, firmer augmentation is required. Small
      filaments of fat are placed in multi-layers throughout the area of the desired
      contour change. Residual processed fat is frozen for second and third injection
      sessions, if needed. These fat transfer methods yield retentions of 20% to 120%
      of the injected volume. After 60 to 90 days the implant is stabilized and becomes
      permanent. Other than bruising, a rare case of bacterial infection, or an
      occasional divot at the donor site, the autologous fat transfer has proved a
      useful method to improve contour defects.

PMID- 11599409
TI  - Brow lifting and blepharoplasty.
AB  - This article addresses how one decides whether to do a brow lift or a
      blepharoplasty using the example of a woman who has paralysis of the frontal
      branch of her left seventh cranial nerve and complete brow ptosis.

PMID- 11599410
TI  - Repair of large and difficult-to-close wounds.
AB  - Large defects may at first appear to be too big to close in a side-to-side
      fashion. Certain wounds and situations may call for healing with second intent.
      Undermining and pulley sutures are very helpful in bringing together wound edges
      of certain large openings. Partial closures may decrease the tendency to exert
      unwanted tension against a free margin, decrease the size of the wound allowed to
      heal with second intent, shorten the duration of healing, and keep scars within
      one cosmetic unit. Buried sutures should be placed and laid beside the wound
      without tying the knot until the surface stitches or the external device
      approximates the wound edges. In this way, one can be certain that the buried
      stitch will provide adequate support to the infrastructure of the wound.
      Intraoperative skin expansion may help close wounds that could not be closed by
      any other technique except for skin grafting.

PMID- 11599411
TI  - Use of skin substitutes in dermatology.
AB  - The use of skin substitutes to treat acute and chronic wounds should continue to
      increase as newer products are developed. The goals for the future are to
      eliminate the need for autografting, eliminate the risk for transmission of
      disease, improve the shelf life and simplify storage requirements, improve
      cosmetic outcomes, and reduce cost. A number of researchers are also looking to
      incorporate gene therapy into skin substitutes.

PMID- 11599412
TI  - Surgical tips.
AB  - A potpourri of practical surgical tips is presented in this article. Included are
      the clues for diagnosis, ideas for wound management, intraoperative tips, and
      assorted other items to enhance surgical practice.

PMID- 11599413
TI  - [Effect of stearoylethanolamine on composition of various classes of lipids in
      rat heart tissue under ischemia-reperfusion].
AB  - The effect N-stearoilethanolamines on lipide classes and their fatty acid
      composition was studied in the isolated rat heart under ischemia--reperfusion. It
      was shown that the amount of cholesterol esters increased at ischemia-
      reperfusion by 4.6 fold. The addition of 10(-7) M, 10(-6) M and 10(-5) M of N
      stearoilethanolamines into perfused solution prevented these negative
      consequences of the myocardium ischemic injury. The addition of N
      stearoilethanolamines decreased the quantity oleinic (18:1 omega 9) and free n-6
      fatty acids. N-stearoilethanolamine lowered the amount of short chain saturated
      fatty acids and also polyunsaturated n-6 fatty acids in cholesterol esters. As
      well the lipide composition of perfused solutions was also investigated.

PMID- 11599414
TI  - [Biochemical mechanism of ulcer development under stressful conditions].
AB  - Using the model of acute immobilizing stress in rats it has been established that
      the content of N-acetylneuraminic acid, hexoses connected with protein, acid
      glycosaminoglycanes and fucouse in a structure of gastric mucus increases
      alongside with growth of proteolytic enzymes activity in it. The received results
      justify an important role of noncollagenic proteins and proteolytic enzymes in
      provision of resistancy of stomach mucous membrane and mechanisms of stressory
      ulcers development.

PMID- 11599415
TI  - [Features of lung tissue cell membrane lipid composition under acute emotional
      stress in rats].
AB  - The lipid composition of the lung plasmatic membrane in rats which have been
      under the acute emotional pain stress action is studied. These results are
      compared with the control group of animals. It is shown that at acute stress the
      changes of lipid composition of the lung plasmatic membranes are manifested in
      decrease the phospholipids and increase of cholesterol levels. The correlation of
      phospholipids/cholesterol in plasmic membranes in the lungs decreases at stress.
      At the same time the decrease of triglyceroles and diglyceroles contents is
      observed as well as the increase of fat acids' number. The changes that take
      place in the lipid contents of the lung plasmatic membranes at acute stress can
      play an essential role in the mechanism of cell damage development.

PMID- 11599416
TI  - [Effect of chronic craving for ethanol on accumulation of calcium ions in
      intracellular structures of rat myometrium].
AB  - In the experiments on the impregnant estrogenized rats the effect of chronic
      ethanol intake on Ca(2+)-accumulative mitochondrial systems and endoplasmatic
      systems of myometrium was estimated. It was defined that in chronic alcohol
      consumption the transport activity of mitochondria Ca(2+)-accumulative systems
      didn't prevail over endoplasmatic reticulum Ca(2+)-accumulative activity.
      Therewith mitochondria and endoplasmatic Ca(2+)-transport system was essentially
      disturbed. In the tested conditions Mg2+, ATP-dependent sensitivity of calcium
      pump to oxytocin inhibiting action was shown to disappear.

PMID- 11599417
TI  - [Oxidative modification of blood plasma proteins in elderly people with vascular
      dementia].
AB  - We examined the spontaneous and metal-ion-catalyzed oxidative modification plasma
      blood proteins in the group of healthy adults and elderly ones and patients with
      vascular dementia (mild and severe). We determined the spectrophotometric
      measurement of 2,4-dinitrophenylhydrazone derivatives formed by reactions with
      protein carbonyls. The level of metal-ion-catalyzed oxidation proteins in the
      aged patients both with and without dementia was high in comparison to the
      healthy adults. The patients with severe dementia showed lower amount of 2,4
      dinitrophenylhydrazone deriviates. Low levels of metal-ion-catalysed protein
      oxidation strongly correlated with the degree of psychoorganic disturbances. The
      elderly persons with both and without dementia showed a high level of plasma
      nonenzymatic H2O2 scavenging in comparison with the healthy adult ones. We
      discovered an imbalance between enzymatic and nonenzymatic components of the
      antioxidant system. The latter indicates that the oxidative modification of brain
      tissue proteins probably plays an important role in aging and mental disorders.

PMID- 11599418
TI  - [Electrochemical sensor based on photopolymeric membranes for determining urea].
AB  - A new electrochemical enzymatic sensor based on the ion selective field effect
      transistors (ISFETs) and photocurable membrane was developed for the
      determination of urea. For the immobilization of urease on the gate surface of
      the ISFET a simple method, involving the use of liquid photocurable compositions
      on the basis of vinylpirollidone, oligouretanemetacrylate and
      oligocarbonatemetacrylate, was applied. The linearange of the response of the
      developed electrochemical sensor lies in the range 0.05-20 mM. The latter
      corresponds to the claims of the medical practice. The overall time of the
      analysis is 5-10 min. The effects of the buffer concentration and its pH as well
      as temperature and presence of ammonia ions in the measuring medium on the
      amplitude of the sensor response were estimated. The duration of sensor work is
      as shortest 40 days. The proposed sensor on the basis of the ISFET is promising
      for the express analysis of the level urea in blood, while the developed method
      of membrane preparation with entrapped enzyme can be combined with the integral
      technology of producing of the biosensors semiconductor transducers.

PMID- 11599419
TI  - [Preparation of bacteria--degraders of alkylnaphthalenesulfonate by a molecular
      breeding method].
AB  - Transconjugant strain of bacteria degraders of alkylnaphthalenesulphonate(ANS)--P
      Pseudomonas alcaligenes TR (NPL-41) was obtained under conditions of ANS
      selective pressure and flow cultivation of bacteria destructors of alkylbenzene
      sulphonate (ABS) P. alcaligenes TR (pABS) and naphthalene P. putida BS438 (NPL
      41) and their immobilization on an inert carrier. Transconjugant P. alcaligenes
      TR(NPL-41) was prepared by means of conjugative transfer of plasmid NPL-41 from
      P. putida BS438 to P. alcaligenes TR. The check out of transconjugant under
      conditions of flow cultivation showed their ability to degradation of ANS.
      Investigation of the stability of plasmid NPL-41 in the transconjugant P.
      alcaligenes TR(NPL-41), obtained by molecular breeding under conditions of flow
      cultivation and by conjugative transfer, showed the transconjugant prepared by
      the former method to be more stable.

PMID- 11599420
TI  - [Use of Pseudomonas and Achromobacter species bacteria--degraders of surface
      active agents--for detection and destruction of polycyclic aromatic
      hydrocarbons].
AB  - The developed biosensor models were based on the use of immobilized Pseudomonas
      and Achromobacter cells for polycyclic aromatic hydrocarbons and surfactants
      detection. The responses of biosensors based on bacteria-degraders of anionic
      surfactants for organic substrates, which related to different classes of
      surfactants, aromatic and policyclic aromatic hydrocarbons (PAH) were
      investigated. The sensor showed the highest sensitivity to anionic surfactants
      and PAH. The lower limit of sodium dodecyl sulfate detection is within a range of
      0.25-0.5 mg/l (0.86-1.73 microM). The sensors showed the highest sensitivity to
      naphthalene (1-6 mM) and anthracene, fluorene, phenanthrene. All strains that
      have been investigated may be used as a receptor element of biosensors for
      detection of PAH and surfactants.

PMID- 11599421
TI  - Prions and protein inhibitors of proteinases: structural analogies and their
      consequences. III. Additive risk factor in transgenic technologies.
AB  - The article presents the risk factor connected with transgenous technologies. The
      probable risk is stipulated by a possibility to produce the proteins capable to
      initiate prion-conditioned neurodegenerative processes as a consequence of
      possible membrane folding of the recombinant protein portion.

PMID- 11599422
TI  - [Regulatory role of low-intensity laser radiation on the status of the
      antioxidant system].
AB  - On the base of modern literary data it is shown that low level laser red
      radiation can render the manifested effect on the activity of main antioxidant
      enzymes. It is determined that the main enzymes of antioxidant system--superoxide
      dismutase, catalase, ceruloplasmine--absorb in the red part of spectrum and are
      capable to be reactive under some regimes of red low level laser irradiation. It
      is one of the main possible mechanisms of biological efficiency of low level red
      laser radiation of the red part of spectrum.

PMID- 11599423
TI  - [Effect of destruction of Escherichia coli cells on the catalytic ability of
      catalase].
AB  - The possibility for investigation of catalase (CAT) activity under the conditions
      of intact E. coli cells was estimated. This approach is based on the possibility
      of hydrogen peroxide freely cross biological membranes. CAT activity of native
      cells had a broad maximum between pH values 4.5 and 7.5. Desintegration of cells
      by freezing--thawing and ultrasonication indicated that there were two CAT
      activity peaks at pH values about 3.5 and 7.0. Activity of CAT with acid pH
      optimum decreased at cell desintegration, but one with neutral pH-optimum was
      rather stable under this procedure. The enzyme in native conditions was less
      sensitive to the inhibition by high concentrations of hydrogen peroxide than its
      counterpart from destroyed cells. Activity of CAT in native and desintegrated
      cell preparations had different sensitivity to heating and inhibition by reduced
      glutathione, but it was inhibited by azide similarly. Difference in the CAT
      properties of native and desintegrated bacteria preparations may be explained by
      different possibility to penetrate cell membrane by reagents and/or by possible
      modification of the enzyme properties at destruction of native microenvironment.

PMID- 11599424
TI  - [Structure-functional modification of lactate dehydrogenase isoforms under the
      effect of ultraviolet radiation and active forms of oxygen].
AB  - The investigation results on the UV-induced changes of lactate dehydrogenase
      structural and functional properties in the presence of some chemical substances,
      which are able to interact with the oxygen active forms have been summarized. As
      well the kinetic characteristics of the photoinactivation processes for heart and
      muscle LDH types in free state and in the complex with the exogenous agents have
      been studied. Singlet molecular oxygen has been shown to play an important role
      in the process of UV-modification of different protein isoforms. The scheme of
      probable physical and chemical processes, leading to the inactivation of lactate
      dehydrogenase molecules, has been suggested.

PMID- 11599425
TI  - [Effect of alpha-tocopherol, tocopheryl quinone and other complexes with
      tocopherol-binding proteins on the activity of enzymes metabolizing arachidonic
      acid].
AB  - alpha-Tocopherol, tocopherylquinon jointly with the proteins tocopherol acceptors
      from cytosole were identified to inhibit the activity of 5-lipoxigenase and so
      the synthesis of leukotriene A4 at the early stages providing for A4 hydrolase
      activation and C4 synthesase, as well as accelerate leukotrienes B4 and C4
      synthesis at the further stages respectively changing the final spectrum of
      leukotriens in the organism tissues. Firstly, the leading role of proteins
      complexes capable to strengthen the effect of alpha-tocopherol and
      tocopherylquinon on arachidonic acid oxidative metabolism was determined.

PMID- 11599426
TI  - [Effect of physiologically-significant stimula on Ca2+/H+ exchange by myometrial
      cell membrane].
AB  - The effect of membrane potential, acetylcholine, carbachol and atropine on the
      myometrium plasmatic membrane Ca2+/H+ exchange was estimated. The change of
      artificially directed membrane potential from -40 to +20 mV was defined to
      provide for increasing the input of Ca2+ into vesicules and output of H+ from
      them in their concentration gradients. The similar changes of cations in
      membranes were registered under acetylcholine (10(-8)-10(-4) M) and carbachol
      (0.1 mM) action. Atropine displayed itself as decreasing the cholinomimetics
      effect to the tested ions transport. The exogenous 0.5 mM Ca2+ free of directed
      membrane potential as well stimulated the output of protons from vesicles. The
      supposition was made regarding H output strengthening and pH possible local
      increase of cytoplasm under the smooth cells activation by the membrane potential
      and acetylcholine.

PMID- 11599427
TI  - [Heme metabolism and oxidative stress].
AB  - The role of heme metabolism in oxidative stress development and defense reactions
      formation in mammals under different stress factors are discussed in the article.
      Heme metabolism is considered as the totality of synthesis, degradation,
      transport and exchange processes of exogenous heme and heme liberated from
      erythrocyte hemoglobin under erythrocyte aging and hemolysis. The literature data
      presented display normal heme metabolism including mammals heme-binding proteins
      and intracellular free heme pool and heme metabolism alterations under oxidative
      stress development. The main attention is focused to the prooxidant action of
      heme, the interaction of heme transport and lipid exchange, and to the heme
      metabolism key enzymes (delta-aminolevulinate synthase and heme oxygenase), serum
      heme-binding protein hemopexin and intracellular heme-binding proteins
      participating in metabolism adaptation under the action of factors, which cause
      oxidative stress.

PMID- 11599428
TI  - [Structural-functional status of the cardiomyocyte cell membrane under
      experimental pathology].
AB  - The results of research conducted on the cardiomyocytes plasma membranes
      structural and functional state under the experimental stress and atherosclerosis
      are displayed in this article. These experimental pathology is determined to be
      accompanied by some stereotypic quantitative and qualitative modifications
      occurred in the lipid matrix of the cardiomyocytes plasma membranes--increase of
      cholesterol content, decrease of phospholipids, accumulation of lisophospholipids
      and fatty acid. There are demonstrated results that the experimental stress has
      an atherogenic effect on the plasma membranes of cells by imputting the
      cholesterol into the membrane even in the intact animals with normal lipid
      metabolism. All these modifications are also accompanied by the activation of
      free-radical oxidation. All these changes are capable to lie in the basis of
      physical and chemical properties mechanism modification of membranes:
      modification of lipid matrix, change of viscosity, ion-transport properties of
      cardiomyocytes membranes, oppression of Na+, K(+)-ATPase activity.

PMID- 11599429
TI  - [Effect of "marine" phospholipids omega-3 fatty acids on the composition of fatty
      acids of rat liver microsomal membrane under oxidative stress].
AB  - As a result of experiments conducted the marine phospholipids preparation
      enriched by omega-3 fatty acids was defined to modify fatty acids content due to
      changes of fatty acids level change in the neutral lipids and phospholipids
      fractions. As well it was identified, that at the oxidative stress induced by
      administration of CCl4 the growth of arachidonic and docozahexaenoic acids in the
      neutral lipids fractions was observed if compare with the norm. At the same time,
      the presented fatty acids in the phospholipids fractions remained unchanged. At
      oxidative stress the phospholipids fraction reacts to levels of arachidonic and
      docozahexaenoic acids just only as a result of administrating phospholipids with
      omega-3 fatty acids. The most attractive is the change of correlation C20:4/C22:6
      -increasing at administration of CCl4 and decreasing both at phospolipids and
      vitamin E injection. Thus, at the oxidative stress the first reacting ones are
      the fatty acids of neutral lipids microsomal membranes.

PMID- 11599430
TI  - [Relationship between polyreactive properties of immunoglobulins and level of
      lipids in them].
AB  - Presented paper deals with the relationship between immunoglobulin polyreactive
      properties and its lipid composition. Serum blood immunoglobulin fraction of an
      intact rabbit as an experimental model was used. Immunoglobulins (Ig) obtained by
      this way were transformed into polyreactive immunoglobulins (PRIg) by treatment
      with chaotropic agent KSCN or reactive oxygen species (ROS) with usage of Fe2+,
      EDTA and ascorbic acid. It was demonstrated that native Ig were able to bind with
      immobilized antigen (ovalbumin) and this ability dramatically increased after
      transformation of Ig into PRIg. The high immunoreactivity of PRIg was associated
      with marked fall (by 2-3 fold) of total phospholipids as well as individual ones-
      sphingomyelin and phosphatidylcholine. The main fatty acids of the Ig and PRIg
      phospholipid fractions in the sequence to decreasing decrease were stearic,
      palmitic, oleic and linoleic acids. The treatment of Ig by chaotropic agent and
      ROS led to decrease of stearic acid and enhancement of oleic, linoleic and
      arachidonic acids. The level of free cholesterol of Ig did not differ from that
      of PRIg. At the same time the content of cholesterol esters of PRIg was
      substantially diminished if compare with Ig. The main fatty acids of the Ig and
      PRIg cholesterol ester fraction in the sequence to decreasing were arachidonic,
      stearic, oleic, linoleic and palmitoleic acids. Transformation of Ig into PRIg
      was accompanied by enhancement of stearic acid level and loss of
      docosapentaenoic, arachidonic and palmitoleic acids. The results presented here
      support the idea about non peroxidative manner of the phospholipid and
      cholesterol ester extrusion from Ig molecule under its transformation into PRIg.
      Rather the last process could be explained by the term of concurrent physico
      chemical interaction of Ig molecule with chaotropic agent or ROS leading to fall
      of lipid content. The presented data for the first time provide us an opportunity
      to conclude that transformation of Ig into PRIG is associated with the marked
      loss of essential phospholipids and cholesterol esters by the Ig molecule. The
      probable implication of this process in development of immune imbalance under
      certain diseases associated with oxidative stress have been discussed.

PMID- 11599431
TI  - [Effect of splenosid on lipid peroxidation process and glutathione antioxidant
      system in rats exposed to fractionated radiation].
AB  - The dynamics of lipid peroxidation, antioxidant glutathione system condition in
      blood and viscerals (brain, heart, liver, spleen) of rats which were fractionally
      irradiated (10 fractions) in the total dose 1.0 Gy and oxidative homeostasis
      increase of primary and secondary lipid peroxidation products and glutathione
      system disturbances were established in the irradiated rats. The administration
      of splenosid diminished the disturbances of oxidative homeostasis but does not
      completely normalize the latter. The administration of splenosid during the
      irradiation course and after its finishing is more effective than only during the
      irradiation course.

PMID- 11599432
TI  - [Activity of the glutathione antioxidant system and cytochrome P-450 in rat liver
      under induction and inhibition of xanthine oxidase].
AB  - The effects of specific xanthine oxidase induction and inhibition on glutathione
      antioxidant system activity, lipid peroxidation, cytochrome P-450 quantity and
      corticosteroids concentration in the rat liver were studied. It was dependence
      established that there was a straight between xanthine oxidase activity and the
      activity of glutathione antioxidant system, lipid peroxidation and the ascorbic
      acid formation. The reciprocal dependence was established between xanthine
      oxidase activity and the concentrations of cytochrome P-450 and corticosteroids.

PMID- 11599433
TI  - [Influence of N-palmitoylethanolamine on the phospholipid and fatty acid
      composition of rat liver in ischemia].
AB  - The effect of N-palmitoylethanolamine (NPE, 10(-5) M) on the lipid peroxidation
      (LPO) processes, phospholipid and fatty acid content in the rat liver at
      perfusion and ischemia during the liver preservation was estimated. As early as
      at the 5th min of perfusion by cooled conserving solution "Eurocollins", LPO
      activation was determined. Simultaneously the content of lysophosphatidylcholine
      (LPC) and phosphatidylserine increased, the total cholesterol level decreased.
      The redistribution of saturated and unsaturated fatty acids quantity was
      detected. The addition of NPE into "Eurocollins" solution reduced the
      accumulation of malonedialdehyde and LPC, modified the fatty acids content. These
      effects, evidently, formed the basis of the protective action of NPE on the
      hepatic tissues under anoxia.

PMID- 11599434
TI  - [Binding of Kunitz-Northrop inhibitor on some sorbents].
AB  - This work is devoted to the problem of sorption and desorption of Kunitz-
      Northrop inhibitor on different sorbents. By passing through Dowex 1.10 column
      0.05 M glycine-NaOH buffer, pH 10, two fractions with 100% inhibitor activity
      were identified, while different admixtures and inert proteins remained resin
      bound. In trypsin-Spheron 300, trypsin-agarose and anhydrochymotrypsin-Spheron
      columns the contamination of sorbents-bound inhibitor complex was eliminated by
      washing out with 0.1 M NaCl, pH 8.0. The resin-bound inhibitor was released at pH
      1. The specific activity of the preparation obtained was shown to increase in 200
      240-fold, but in the case of anhydrochymotrypsin-Spheron 300 the inhibitors
      activity was detected both at pH 8.0 and pH 1.7. In this case the increase in
      specific activity was only 2 and 68-fold, respectively. The most effective
      inhibitor-peptide desalting was defined at application of dialysis membranes
      "Spectra/Por" (MWCo: 3000-5000 USA). While applying PAAG electrophoresis the
      standard SDS-system were shown to be ineffective. Therefore some modifications of
      this method were used. Being compared with molecular weight of Contrycal and
      other known peptides this preparation revealed the presence of protein
      contamination. Within 1-9 mg the peptides demonstrated a linear dependence in
      trypsin inhibition. The weight and molar ration of inhibitor: trypsin was found
      to be 1:1 and 3:1, respectively. It was calculated that IUE of the inhibitor had
      inhibited 0.73 mg of trypsin, IUE of Contrycal--0.15 of the enzyme, that was 4.6
      fold less effective than the separated peptide.

PMID- 11599435
TI  - [Investigation of N-acylethanolamines on adrenal cortex function].
AB  - The possibility of NAE to take part in the regulation of the function of adrenal
      glands was studied. It was shown that two times NAE (18:0) injection in a dose 5
      mg/kg of weight increased the content of 11-hydroxysteroids in blood of intact
      male rats. NAE caused the raise of the blood hormone content in 4 fold under the
      immobilization stress. It is apparent that augment of stress response under the
      influence of NAE in vivo is explained by the activation of hypophysis-adrenal
      cortex system. In vitro NAE lowered steroidogenesis by near 40%. One can suggest
      that this decrease is caused by membranotropic properties of NAE.

PMID- 11599436
TI  - Moderating menu to lighten load.

PMID- 11599437
TI  - [Modelling of prevalence development in a paratuberculosis control program in a
      dairy herd].
AB  - A modelling approach to calculate the success of a paratuberculosis control
      programme in dairy herds is presented. The essential parameters of the model are
      the prevalence at the beginning of the programme, diagnostic sensitivity and
      specificity of the tests used, discipline in culling test-positive animals,
      turnover in the herd, percentage of replacement with own stock and
      paratuberculosis prevalence in animals bought into the herd from outside, and a
      general hygiene-based factor. Diagnostic measures and time schedule used in the
      modelling approach are given by the paratuberculosis-control-programme of the
      local board for infectious disease control in food animals in the state of Lower
      Saxony. It was found by the model-calculations that in case of a high initial
      prevalence the anticipated six-year duration of the control programme is
      justified in order to ensure a lasting improvement of herd health. If hygienic
      measures are strictly obeyed and all test positive animals are culled a clear
      reduction on paratuberculosis prevalence can be achieved within the first year.
      According to the model in the second and third year the prevalence will increase
      again despite ongoing diagnostic measures in order to decrease again continuously
      with the beginning of the fourth year. Given an initial prevalence of 10%, 20% or
      30% the prevalence after six years is calculated to be at 3%, 5% or 8% when all
      measures are followed as given in the control programme. The presented programme
      seems to be appropriate to predict prevalence development in paratuberculosis
      infected dairy herds if the herds are managed according to the guidelines of the
      "Tierseuchenkasse Niedersachsen", the local board for infectious disease control
      in food animals in the state of Lower Saxony, Germany. It becomes apparent that
      within six years a high decrease of the prevalence in the herds, but not a
      complete eradication of disease can be achieved by consistently complying with
      the rules given in these guidelines.

PMID- 11599438
TI  - [Quantitative occurrence of lipolytic and proteolytic enzymes in food of animal
      origin].
AB  - Proteolytic and lipolytic enzymatic activities of microorganisms are the most
      important cause for food spoilage and a limited shelf life. Until now the
      determination of the total aerobic count is the base of shelf life evaluations.
      Our investigations show the proportion of proteolytes and lipolytes to the total
      germ count in different kinds of food (milk and milk products, meat products and
      fish) which is in part surprisingly high. Results were observed on different
      media--proteolytic germs were counted on protein containing agar (casein, meat
      protein, fish protein) and lipolytic organisms on fat containing agar
      (tributyrin, olive oil, butterfat). Using the predictive microbiology and the
      knowledge about the activity of microbial enzymes under different milieu
      conditions in food the results give an important tool for a better shelf life
      evaluation.

PMID- 11599439
TI  - Virus isolation and vaccination of Mediterranean tortoises against a chelonid
      herpesvirus in a chronically infected population in Italy.
AB  - A chelonid herpesvirus was isolated from a group of tortoises in Italy with a
      history of increased mortality and upper digestive and respiratory tract disease.
      The isolated virus was inactivated with formalin and used to prepare a
      nonadjuvanted vaccine and a vaccine adjuvanted with aluminum hydroxide. 57
      tortoises, 26 Testudo hermanni, 25 T. graeca, and 6 T. marginata, were included
      in the study. The animals were vaccinated 3 times at 45 day intervals. Blood was
      collected from the animals 14 days prior to the first vaccination, and on day 0,
      25, 45, 90, 113 and 369 after the first vaccination. Plasma antibody titers to
      the homologous chelonid herpesvirus were determined using a virus neutralization
      test (VNT). No significant rise in antibody titer was noted in the vaccinated
      animals. Antibody titers measured dropped below the cutoff-level sporadically in
      all positive animals. Repeat serological testing may therefore be necessary in
      order to detect seropositive animals.

PMID- 11599440
TI  - [The Hannover School of Veterinary Medicine in the Third Reich. Part 1: early
      history, assumption of power and consolidation of the Nazi regime].
AB  - During the time of the Weimar republic the professors and students at the School
      of Veterinary Medicine Hannover had a national-conservative political attitude
      with a clearly anti-republican tendency. Before 1933 the National Socialism did
      not play a role at the school. After the assumption of power by Hitler the
      'Gleichschaltung'--which also took place at the universities--ran mostly smoothly
      at the veterinary school. 75% of the teaching staff and 50% of the students had
      joined the NSDAP (nazi party) respectively the NSDStB (nazi student organisation)
      at the end of the summer semester 1933. The following development of the school
      until World War II is closely connected with the foundation of the Military
      Veterinary Academy in Hannover in 1935. During the years 1935-1939 offerings were
      made in a traditional way and without political considerations playing a major
      role. With the beginning of World War II the school developed into the centre of
      veterinary studies in Germany. In order to meet the demand of veterinary officers
      and civil veterinarians the studies were shortened, trimesters were temporarily
      introduced und standards of examinations were lowered. At the end of the war
      around 45% of the school was destroyed. In the beginning the denazification meant
      a significant turning point but it developed into a mere episode of the history
      of the school by the reappointment of all the seven professors who had been
      dismissed in 1945/46.

PMID- 11599441
TI  - Cilia-Associated Respiratory (CAR) bacillus infection in veal calves and adult
      cattle.
AB  - Cilia-Associated Respiratory (CAR) bacillus is a filamentous bacterium that
      colonizes the ciliated epithelium of the respiratory tract of many animal species
      and that has been associated with chronic inflammatory lesions in naturally and
      experimentally infected rats, mice and rabbits. In the present study, the
      prevalence of CAR bacillus infection and histological lesions of the trachea in
      veal calf and adult cattle were investigated. Forty five healthy veal calves and
      45 adult cattle, raised in 18 different herds were selected at slaughter. From
      each animal, a tracheal sample was processed for histology, stain-ed with the
      Warthin-Starry method to evaluate the presence of CAR bacillus, and with
      haematoxylin and eosin to evaluate the presence of inflammatory lesions. CAR
      bacillus was identified in 17 veal calves (37.7%) and in 7 adult cattle (15.5%).
      Inflammatory lesions were found in 42 veal calves (93.3%) and in 41 adult cattle
      (91.1%). Statistical analysis pointed out a significant correlation between the
      presence and number of CAR bacilli and the presence and number of lymphoid
      follicles (P = 0.0071) and the presence and severity of neutrophilic infiltrates
      (P = 0.0428). These results indicate that CAR bacillus infection is common in
      cattle and is correlated with tracheal inflammatory lesions.

PMID- 11599442
TI  - Application of western blotting procedure for the immunodiagnosis of visceral
      larva migrans in mice by using excretory/secretory antigens.
AB  - A Western blotting procedure with excretory/secretory antigens from Toxocara
      canis larvae was developed for immunodiagnosis of visceral larva migrans in mice.
      In this study, eighty Swiss albino mice were allotted into two groups of 40 each
      as control and experimental groups, and T. canis ova containing infective larvae
      were given to mice in the latter group to form visceral larva migrans. Blood
      samples were taken from 5 infected and 5 control mice on days 25, 30, 35, 40, 45,
      50, 55, and 60 after infection. After bleeding, the mice were necropsied. Slides
      were prepared from their brain tissues and examined for visceral larva migrans.
      Following this procedure, their guts were also examined for intestinal parasites.
      Protein bands of excretory/secretory antigens of 2nd stage larvae of Toxocara
      canis were determined by using SDS-PAGE. Sera from the mice were tested by
      Western blotting and results were compared to the protein bands obtained by SDS
      PAGE to determine specific bands. Specific protein bands for visceral larva
      migrans were determined as 24, 28, and 48 kDa according to our test results.

PMID- 11599443
TI  - Pharmacodisposition of thiamphenicol in rabbits.
AB  - The pharmacokinetic parameters of thiamphenicol (TAP) were studied in New Zealand
      white rabbits. Five rabbits were each given thiamphenicol as a single 30 mg/kg of
      body weight dosage by intravenous (i.v.), intramuscular (i.m.) and oral routes.
      Serum antibacterial concentrations were determined for 72 h after dosing.
      Compartmental modeling of the i.v. administration indicated that a 2-compartment
      open model best described the disposition of thiamphenicol in rabbits. Serum
      thiamphenicol concentrations after i.m. and oral dosing were best described by a
      1- and 2-compartment model, respectively. Overall elimination half-lives for
      i.v., i.m. and oral routes of administration were 1.39, 2.45, and 1.44 h,
      respectively. The half-life of absorption for oral dosing was 1.2 times the half
      life of absorption after i.m. dosing (0.49 h vs 0.40 h). The calculated time to
      maximal serum concentration was 1.25 h after i.m. dosing and 1.17 h after oral
      administration. The calculated serum concentrations at these times were 80.4 and
      69.8 micrograms/ml, respectively. Mean residence time's were 1.89 h for i.v.
      injection, 2.78 h for i.m. dosing and 4.11 h for oral administration.
      Thiamphenicol was widely distributed in the rabbit as suggested by the volume of
      distribution value at steady state of 1.47 l/kg calculated from the i.v. study.
      Bioavailability was 101.4% after i.m. dosing and 64.2% for oral absorption.

PMID- 11599444
TI  - Clinical governance for neurosurgeons: a perspective from the United Kingdom.

PMID- 11599445
TI  - The role of endoscopic biopsy and third ventriculostomy in the management of
      pineal region tumours.
AB  - The best surgical strategy for treating patients with pineal tumours presenting
      with acute hydrocephalus remains undermined. During the past 17 years we have
      used transventricular endoscopic biopsy and third ventriculostomy as a one-step
      procedure in the initial management of these cases, and present the largest
      consecutive case series illustrating the value of this technique. We have
      successfully managed 34 consecutive patients with pineal region tumours, carrying
      out third ventriculostomy in 18 patients. Histological diagnosis was obtained in
      32/34 (94%) of the cases. There were no deaths or major complications and only
      one patient required a ventriculo-peritoneal shunt owing to ventriculostomy
      failure. According to current management protocols and depending on histology,
      tumours were treated by a combination of resection via craniotomy followed by
      radiotherapy or chemotherapy, or by the latter therapies alone. This one step
      procedure is minimally invasive and safely achieves adequate biopsy with control
      of hydrocephalus, whilst definitive histology and biochemical marker studies are
      obtained. Definitive treatment for each tumour is designed according to
      diagnosis.

PMID- 11599446
TI  - Adverse operative events in neurosurgical training: incidence, trends and
      proposals for prevention.
AB  - We prospectively studied the adverse operative events encountered during the
      first 4.5 years of a single neurosurgeon's career (JP). We investigated the
      incidence of these events and their distribution over time, and recorded risk
      factors in causation. Twenty-three adverse events were identified in 728 cases
      studied. These all occurred in one of four categories of operation: craniotomy,
      shunt placement, spinal surgery and stereotactic biopsy. The incidence of adverse
      operative events varied between 5.8% for spinal operations to 9.5% for
      stereotactic biopsy. There was evidence of a reducing incidence of adverse
      operative events over time in some operative groups. The two categories with the
      highest incidence of adverse operative events were the same two categories with
      the lowest number of assisted cases per 100 operations performed.

PMID- 11599447
TI  - Prospective study of clinical and radiological outcome after anterior cervical
      discectomy.
AB  - Most surgeons undertaking anterior cervical discectomy (ACD) introduce a bone
      graft or cage into the disc space when the decompression is complete to prevent
      segmental collapse and preserve cervical spine alignment. We have conducted a
      prospective observational cohort study to investigate the relationship between
      cervical spine alignment and clinical outcome in 55 patients undergoing ACD
      without interbody graft or cage. At 12 months, the overall alignment of the
      cervical spine and the presence of segmental kyphosis at the operated level were
      correlated with clinical outcome measured by SF 36, Neck Disability Index and
      visual analogue neck pain score. Loss of the overall cervical lordosis was
      present in 30 patients and segmental kyphosis was found in 18. Analysis of
      clinical outcome showed no statistical differences between patients with
      preserved and abnormal cervical and segmental alignment. Disturbance of cervical
      and segmental alignment is common in patients following cervical discectomy, but
      does not appear to compromise clinical outcome at 12 months.

PMID- 11599448
TI  - Bedside external ventricular drain placement for the treatment of acute
      hydrocephalus.
AB  - The purpose of this retrospective study was to evaluate the results of external
      ventricular drain (EVD) placement for the management of hydrocephalus. We present
      our experience with 103 consecutive cases over one year, 56 of which had
      subarachnoid hemorrhage (SAH). Short tunnel ventriculostomy was performed at the
      bedside in the neurosurgical intensive care unit (NSICU), using sterile
      technique. Long-term care included meticulous site care by a dedicated NSICU
      nurse, daily cultures and prophylactic antibiotics. The average duration of EVD
      was 10.7 days (range 1-28 days). There was one case of positive cerebrospinal
      fluid (CSF) culture. Additional complications included one small intraparenchymal
      hematoma and two cases of EVD disconnection. No patient died form EVD-associated
      complications. No rebleed from aneurysmal SAH was seen. There was no correlation
      between the duration of EVD and infection. We conclude that placement of short
      EVD in the NSICU is safe and can be maintained for the required duration of
      treatment with minimum infection rate.

PMID- 11599449
TI  - Establishment of primary human meningiomas as subcutaneous xenografts in mice.
AB  - Meningiomas are the most frequently occurring benign central nervous system
      tumours. We determined whether a subcutaneous animal model of meningioma was
      feasible by implanting fresh meningioma tissue from six patients into 60 athymic
      (nude) mice, either as tissue blocks (38 mice) or as cell suspensions (22 mice).
      The tumour take-rates were 74% (block) and 50% (suspension), and the xenografts
      retained the original tumour grade and subtype morphology by light microscopy.
      Comparison of cell proliferation markers in xenografts and original tumours gave
      similar immunohistochemical score rates for Ki-67, but not for PCNA. With the
      exception of one atypical tumour surgical specimen, all tumours lacked p53
      immunopositivity. Transmission electron microscopy of sections of tumour
      xenografts revealed ultrastructural features, including desmosomes and desmosome
      like structures, characteristic of well-differentiated meningiomas. The
      xenografts grew progressively with a volume increase of more than 10-fold over 6
      11 months and an apparent doubling time of 16 weeks. This study demonstrates the
      utility of the subcutaneous meningioma xenograft as a model for further
      biological and therapeutic studies.

PMID- 11599450
TI  - Spinal cord stimulation--a long-term evaluation in patients with chronic pain.
AB  - Spinal cord stimulation (SCS) is an established treatment modality for chronic
      pain, angina pectoris, and peripheral vascular disease. This study evaluates
      experience with SCS over a 13-year period with emphasis on surgical
      complications, revisions and pain relief. It took the form of a retrospective
      study of medical/surgical records coupled with a postal/telephone questionnaire.
      The subjects consisted of seventy patients, aged from 21 to 76 years (mean 47;
      median 46), with severe, chronic pain refractory to conventional treatment, who
      underwent SCS implantation between 1984 and 1997. It investigated surgical
      revisions, complications and pain relief. There were 72 surgical revisions
      comprising electrode replacement/repositioning (32), generator replacement (22),
      cable failure (6) and implant removal (12). Half the devices were revised within
      3 years (95% confidence interval: 2-5 years) of implantation. Six (8.6%) implants
      became infected. Sixty per cent of patients reported substantial relief of pain.
      This study shows that the majority of patients undergoing SCS derive significant
      benefit in terms of pain relief, but commonly require surgical revisions due to
      both technical and biological factors. These devices require systematic
      evaluation to determine optimal usage, clinical effectiveness and cost-benefit
      analysis.

PMID- 11599451
TI  - Crisis in resources: a neurosurgical prospective.
AB  - In the light of the recent recommendations of the Society of British Neurological
      Surgeons on safe neurosurgery, we prospectively audited the work load,
      availability and efficiency in the use of neurosurgical resources in our
      department over a 1-month period. There were a total of 130 admissions--70
      emergency and 60 elective cases. Twenty-three patients referred as emergencies
      were denied admission, directly or indirectly, because of shortage of beds. Other
      emergency cases had to wait unacceptable long periods, up to 17 days, prior to
      admission for the same reason. For elective cases, there was a 33% cancellation
      rate due to lack of beds and competition with the emergency cases for the same
      resources. Overall bed occupancy rate exceeded 100%. We conclude that the current
      neurosurgical resources are inadequate and over-stretched leaving no safety
      margin. Neurosurgery as a core emergency service, therefore, should be given
      priority in NHS resource allocation.

PMID- 11599452
TI  - Sildenafil (Viagra)-induced spontaneous intracerebral haemorrhage.
AB  - Sildenafil (Viagra) has been developed as a drug to help male impotence. It has a
      direct effect on the vasculature of the corpus cavernosum. A case of spontaneous
      intracerebral haemorrhage (ICH) following the illicit use of Viagra is reported.
      A discussion of drug-induced ICH is included.

PMID- 11599453
TI  - Parafalcine meningioma presenting with facial pain: evidence for cortical theory
      of pain?
AB  - Intracranial tumours causing facial pain are very rare. All previously reported
      tumours have been located in either the posterior or middle fossa. We present a
      unique case of a bilateral parasagittal meningioma located in the parietal
      occipital cortex presenting with right-sided facial pain.

PMID- 11599454
TI  - Low pressure hydrocephalus: issues of diagnosis and treatment in five cases.
AB  - Five patients with hydrocephalus who failed to respond to apparently adequate CSF
      drainage via a functioning shunt (four cases) or external ventricular drain (one
      case) are described. In three of the four shunted cases, the shunt was
      ventriculoperitoneal with a medium pressure valve, and in one a combination of
      peritoneal and atrial shunts both with low pressure valves. All five patients
      were tested for possible low pressure hydrocephalus by a period of external
      ventricular drainage at heights of 0 to -5 cm H2O below the reference point
      (external auditory meatus--EAM). Four of the five patients showed rapid and
      significant clinical improvement and went on to shunt revision (three) or
      insertion (one). The shunts were then all peritoneal, of which three were
      valveless, whilst one had a Sophy programmable valve at the lowest setting. In
      all four patients the improvement was sustained and was associated with a
      radiological (CT or MRI) improvement which varied from marked to slight. In the
      fifth patient there was no improvement with low pressure external drainage and no
      shunt revision was undertaken. On the basis of these cases the possible entity of
      low pressure hydrocephalus is discussed with particular reference to mechanism,
      recognition and management.

PMID- 11599455
TI  - Transradicular interfascicular approach for lumbar microdiscectomy: a useful
      technique in difficult circumstances.
AB  - Nerve root retraction is a component of lumbar disc surgery. The authors describe
      a transdural approach for lumbar microdiscectomy through the nerve root, instead
      of retracting the root. This technique can be safely used in rare cases where
      root manipulation is considered to be difficult and dangerous.

PMID- 11599456
TI  - Life threatening complication of biocompatible osteoconductive polymer graft
      after anterior cervical discectomy.
AB  - Graft extrusion following anterior cervical discectomy is a recognized
      complication. We report a case of acute laryngeal obstruction secondary to
      synthetic graft extrusion to highlight potential dangers of interbody spacing
      devices and to stress the importance of investigation of patients who have
      symptoms attributable to early graft extrusion.

PMID- 11599457
TI  - Focal bony outgrowth of the cranium: difficulties in diagnosis of extracranial
      meningioma.

PMID- 11599458
TI  - Healed medieval cranial weapon injury from Coventry.

PMID- 11599460
TI  - Effect of inseminated volume on intrauterine insemination.
AB  - PURPOSE: Intrauterine insemination (IUI) is a method for the treatment of marital
      infertility involving the intrauterine or fallopian deposition of washed
      spermatozoa, depending on the amount of inseminated semen. In view of the
      divergent opinions about the inseminated volume, the objective of this study was
      to compare the two techniques (3.0 mL or 0.5 mL) in two groups of patients.
      METHODS: We performed 164 cycles of ovulation induction followed by IUI. The
      patients were divided into two groups according to the technique used. Group low
      volume--50 cycles and 0.5 mL of inseminated semen; Group high volume--114 cycles
      and 3.0 mL of inseminated semen. The cycle was monitored on the basis of
      endometrial thickness and follicular development measured by transvaginal
      ultrasound. Human chorionic gonadotrophin (hCG) was administered in the presence
      of a follicle measuring 18 mm in mean diameter. The procedure was performed after
      sperm washing using a discontinuous PureSperm gradient, 40 h later. RESULTS: We
      obtained a similar clinical pregnancy rate for the two groups (14.0% for Group
      low volume and 15.7% for Group high volume). There was one abortion in each
      group. We detected no interference by any etiology of infertility or by the total
      motile recovered sperm with pregnancy rate. CONCLUSIONS: The results did not
      demonstrate superiority of one method over the other, with both therapeutic
      alternatives being satisfactory for the treatment of infertile couples.

PMID- 11599459
TI  - Follicular fluid enhances sperm attraction and its motility in human.
AB  - PURPOSE: Follicular fluid has a pivotal effect on motility and chemotaxis of
      spermatozoa for successful fertilization. The effect of human follicular fluid
      (hFF) and progesterone on attraction and motility of spermatozoa were
      investigated using simplified capillary assays. METHODS: Capillary tubes loaded
      with hFF, modified human tubal fluid (m-hTF), or m-hTF supplemented with
      progesterone, respectively, were used for assessments of attraction and motility
      of spermatozoa following culture at various time intervals. RESULTS: Number and
      motile ratio of spermatozoa in the tubes loaded with hFF were significantly (P <
      .05) higher than those with m-hTF. In the tubes loaded with m-hTF, m-hTF
      supplemented with progesterone, and hFF, the attracted number of spermatozoa were
      34 x 10(5), 131 x 10(5), and 108 x 10(5), and motile ratio of spermatozoa was 37,
      48, and 82%, respectively. CONCLUSIONS: We conclude that hFF clearly plays a
      crucial role in enhancing attraction and motility of spermatozoa, and
      progesterone has strong effect on attraction of spermatozoa.

PMID- 11599461
TI  - Effects of growth hormone on in vitro maturation of germinal vesicle of human
      oocytes retrieved from small antral follicles.
AB  - PURPOSE: Evaluation of the effect of GH, administered in vivo, on in vitro
      maturation of human GV oocytes obtained from small follicles. METHODS: The study
      included 88 ICSI women stimulated with long agonist protocol. They were randomly
      allocated to two groups (Group 1, 44 women with 86 GV oocytes), were cotreated
      with GH (Group 2, no GH: 44 women with 67 GV oocytes). GV oocytes from small
      follicles were matured in vitro, injected, and their development observed.
      RESULTS: Resumption of meiosis was significantly higher in Group 1 compared to
      Group 2 (60 and 37.3% respectively). Significantly more M2 oocytes were obtained
      in Group 1 than in Group 2 (45.5 and 23.9% respectively). Fertilization rates
      were also significantly higher (51.9 and 18.8% respectively). No embryos were
      obtained in Group 2, whereas 21.1% of fertilized oocytes in Group 1 cleaved into
      class A embryos. CONCLUSION: In vivo administration of GH enhanced in vitro
      maturation and fertilization of human GV oocytes retrieved from small antral
      follicles.

PMID- 11599462
TI  - Oocyte comet assay of luteal phase sera from nonpregnant patients after assisted
      reproductive procedures.
AB  - PURPOSE: Serum factors in patients with recurrent spontaneous abortions (RSA)
      inhibit mouse embryo development in vitro. Serum factors affecting DNA integrity
      remain to be tested. The null hypothesis was that patient sera do not affect DNA
      integrity. The objectives were (a) to use the oocyte comet assay to assess DNA
      damage after exposure to patient sera and (b) to determine the effect of sera
      from gravidity 0 parity 0 patients to induce DNA apoptosis. METHODS: Luteal phase
      sera were drawn 1 week after embryo transfer following assisted reproductive
      procedures. Frozen-thawed hamster zona intact oocytes at metaphase II were
      incubated in groups of eight in either control medium or medium supplemented with
      50% patient serum for 1.5 h at 37 degrees C in room air. The oocytes were fixed,
      stained in acridine orange, embedded in agarose, lysed, and alkaline
      electrophoresis performed. The intensities of the digitized fluorescent images
      were analyzed. RESULTS: The sera of nonpregnant patients (64%) caused significant
      fragmentation of hamster oocyte DNA when compared with pregnant patient sera.
      This difference was also observed when adjusted for patient age. Sera of patients
      that had never been pregnant also resulted in oocyte DNA fragmentation.
      CONCLUSIONS: The results suggested that sera from patients that did not conceive
      contained factors that did not support cell growth by causing DNA fragmentation
      and apoptosis. The level of the apoptotic factors varied from cycle to cycle.
      However, more studies are needed to determine if the sera factors actually reach
      the uterine environment to cause the undesirable effects.

PMID- 11599463
TI  - Performing ICSI using an injection pipette with the smallest possible inner
      diameter and a long taper increases normal fertilization rate, decreases
      incidence of degeneration and tripronuclear zygotes, and enhances embryo
      development.
AB  - PURPOSE: To compare the efficacy of two types of injection pipette used for ICSI,
      one with a larger (5-7 microns) inner diameter and a shorter taper with that
      inner diameter, and another with the smallest (3-5 microns) possible inner
      diameter and a longer taper with that inner diameter. METHODS: Retrieved oocytes
      at metaphase II stage were injected using one of two types of injection pipette,
      in 33 and 94 cycles, respectively, in a total of 127 cycles in 108 patients.
      RESULTS: In comparison to the injection pipette with a larger (5-7 microns) inner
      diameter and a shorter taper with that inner diameter, the injection pipette with
      the smallest (3-5 microns) possible inner diameter and a longer taper with that
      inner diameter increased normal fertilization rate ((70 +/- 3.6)% vs. (86 +/-
      2.2)%; P = .001; mean +/- SEM); decreased the incidence of degeneration ((14 +/-
      2.4)% vs. (5 +/- 1.4)%; P = .001) and tripronuclear zygotes ((1.0 +/- 0.35)% vs.
      (0.1 +/- 0.21)%; P = .03); increased Day-2 diploid embryos ((69 +/- 3.7)% vs. (85
      +/- 2.2)%; P = .001) and good-quality Day-2 diploid embryos ((67 +/- 4.0)% vs.
      (79 +/- 2.4)%; P = .03), all per injected oocyte; and increased the number of
      blastomeres per good-quality Day-2 diploid embryo ((3.0 +/- 0.21 vs. 3.8 +/-
      0.12; P = .0003). CONCLUSIONS: Performing ICSI using an injection pipette with
      the smallest (3-5 microns) possible inner diameter and a longer taper with that
      inner diameter maximizes normal fertilization rate, minimizes the incidence of
      postinjection degeneration and tripronuclear zygotes, and enhances embryo
      development.

PMID- 11599464
TI  - Uterine perfusion and hormonal pattern in patients with polycystic ovary
      syndrome.
AB  - PURPOSE: To evaluate whether polycystic ovary syndrome (PCOS) patients with
      different pulsatility index (PI) of uterine artery showed differences in their
      hormonal pattern. METHODS: Eighty-eight PCOS-affected patients and 15 controls
      were submitted to Doppler flow measurement of uterine artery; LH, FSH PRL,
      estradiol, and androgens concentration determination; and BMI evaluation during
      early follicular phase. RESULTS: The mean PI of uterine artery of PCOS patients
      was significantly higher than control group (2.97 +/- 0.9 vs. 1.89 +/- 0.2
      respectively). The distribution of the PI'values was significantly different in
      the PCOS-affected patients and in control group. The plasma levels of DHEAS and
      BMI were significantly higher in PCOS patients with PI > or = 3 than in PCOS
      patients with PI < 3. CONCLUSION: High resistance in the uterine artery is
      present in PCOS patients, but a wide range PI values of uterine artery is
      present. BMI and DHEAS seem to be factors interfering with uterine perfusion.

PMID- 11599465
TI  - Human reproductive cloning and related techniques: an overview of the legal
      environment and practitioner attitudes.
AB  - PURPOSE: This study provides an overview of the legal environment and assisted
      reproductive technology (ART) practitioner attitudes toward human reproductive
      cloning. METHODS: A review of the law and a survey of ART practitioners and a
      comparison group of attorneys were undertaken. RESULTS: Human reproductive
      cloning has been prohibited in many countries, and may soon be prohibited in
      others. However, many ART practitioners support its use for limited indications.
      CONCLUSIONS: ART practitioners were surveyed concerning their views on human
      reproductive cloning and related techniques. A few had considered using or had
      used embryo splitting or germ cell nuclear transfer. Although they expressed some
      concerns about the present risk of reproductive cloning, most indicated that it
      did not violate their religious beliefs. More than three-quarters of ART
      practitioners responding indicated that they would be willing to provide human
      reproductive cloning in indicated cases if it were legally permissible to do so.
      A significant percentage of the group also indicated that they currently have the
      ability to provide this service.

PMID- 11599467
TI  - Reprogramming somatic cell differentiation and the Hayflick Limit: contrasting
      two modern molecular bioengineering aims and their impact on the future of
      mankind.
AB  - The molecular biology of human cloning and aging research depend on the closely
      related laboratory techniques supported by a thorough understanding of cell
      signaling processes. Unfortunately, the link between these two research fields
      has received only marginal attention in the lay press. Cloning is possible when
      somatic cell differentiation is successfully reprogrammed, and clinical control
      of cellular senescence depends on a proper reconfiguration of the predetermined
      number of divisions permitted during the cell life-cycle (the so-called "Hayflick
      Limit"). In this paper, we discuss these two concepts and compare the impact
      likely to be associated with bioengineering studies that facilitate both human
      cloning and longevity therapy.

PMID- 11599466
TI  - Cloning in reproductive medicine.
AB  - This review article summarizes the historical development of mammalian cloning,
      presents current advances and presumed risk factors in the field of reproductive
      cloning, discusses possible clinical applications of therapeutic and diagnostic
      cloning and outlines prospective commercial trends in pharmaceutical cloning.
      Predictable progress in biotechnology and stem cell engineering should prove to
      be advantageous for patients' health and for novel benefits in reproductive and
      regenerative medicine.

PMID- 11599468
TI  - Statement of opinion on the subject of "human reproductive cloning".

PMID- 11599469
TI  - Cloning.

PMID- 11599470
TI  - An opinion on human reproductive cloning.

PMID- 11599471
TI  - Cloning humans?

PMID- 11599472
TI  - Cloning and risk factors.

PMID- 11599473
TI  - [Initial sequence and analysis of the human genome].

PMID- 11599474
TI  - [The thread and the labyrinth. Use and applications of DNA microarrays in the
      genomic sciences].

PMID- 11599475
TI  - [Repeated elements in the human genome: junk DNA or genomic treasure?].

PMID- 11599476
TI  - [The human genetic variability map, single nucleotide polymorphisms (SNP's) and
      some of their applications to medicine].

PMID- 11599477
TI  - [Guillain-Barre syndrome. Experience in a third level hospital].
AB  - INTRODUCTION: Acute peripheral neuropathy represents a medical emergency. The
      causes of it are diverse and plentiful. The most common cause of acute paralytic
      peripheral neuropathy is the Guillain-Barre syndrome (GBS). As many as 85% of
      those affected can be expected to make an excellent recovery. OBJECTIVE: To
      describe the principal risk factors associated, clinical manifestations,
      treatment, evolution and complications of 28 cases of Guillain-Barre syndrome
      (GBS) in the "Instituto Nacional de Ciencias Medicas y Nutricion Salvador
      Zubiran". METHODS: We search in our computer records all files under diagnostic
      of GBS, during the last ten years. We found 28 cases that were available to
      study. RESULTS: Mean age was 37 years old (SD 17.2). Fifteen patients were female
      (54%) and 13 were male (46%). Nine patients (32%) were preceded by a superior via
      infection, 5 (18%) by a diarrhea illness and 14 patients had not a predisposing
      factor. The duration of symptoms before diagnostic has a median of 7 days (2-15).
      Twenty-six patients (93%) had an ascending paralysis and 18 had paresthesias
      (64%). The most frequent subtype was acute inflammatory-demyelinating
      polyneuropathy (AIDP) in 18 patients (64%), acute motor-sensory axonal neuropathy
      (AMSAN) in 5 (18%), acute motor axonal neuropathy (AMAN) in 3 (11%) and 2
      patients (7%) had the Fisher-Miller syndrome. Fifteen patients (54%) developed
      respiratory involvement requiring mechanical ventilation. Twenty-four patients
      (86%) had cerebrospinal fluid proteins elevated. Twenty patients (72%) had a
      total recovery, 6 (21%) had a partial recovery and 2 had not any response (7%).
      DISCUSSION: GBS is a particularly highstakes illness in that its onset is sudden
      and paralysis is frequently extreme (requiring assisted respiration), however, as
      many as 85% of those affected can be expected to make an excellent recovery. In
      our study the majority of patients (54%) develop respiratory involvement
      requiring mechanical ventilation but in this group the majority had a favorable
      outcome (71%).

PMID- 11599478
TI  - [Drug resistance of Mycobacterium tuberculosis in Orizaba, Veracruz. Implications
      for the tuberculosis prevention and control program].
AB  - BACKGROUND: Tuberculosis, declared a global emergency by the World Health
      Organization, continues to be an important public health problem in Mexico,
      included in the first twenty causes of death. OBJECTIVE: To know the impact of
      drug resistance of Mycobacterium tuberculosis on treatment outcome, need of re
      treatment and mortality in a cohort of patients with pulmonary tuberculosis
      receiving directly observed therapy, short course (DOTS). METHODS: We conducted a
      population-based study in a suburban region in Southern Mexico. People who had
      been coughing for more than two weeks underwent sputum acid-fast bacilli smear.
      Patients with a positive smear were recruited and underwent clinical exam, chest
      X-ray, HIV testing, and sputum cultures. Identification, drug susceptibility
      testing and restriction fragment length polymorphism analysis (RFLP) were
      performed in all isolates. Patients were followed every 12 months for new
      episodes of tuberculosis and vital status. Patients were referred for clinical
      care to the local program of tuberculosis. Deaths were corroborated with death
      certificates. Informed consent was obtained from participants. RESULTS: Between
      March 1995 and February 1999, tuberculosis was diagnosed in 371 patients who were
      followed for an average of 32 months. M. tuberculosis was cultured from 316
      patients; resistance to any drug occurred in 25.0% of isolates (primary 18.8%,
      acquired 49.2%); only to isoniazid in 6.8% (primary 7.3%, acquired 4.8%); to
      isoniazid and rifampin in 6.2% (primary 1.6%, acquired 23.8%). Patients with drug
      resistance had a higher probability of treatment failure (OR = 16.9, CI 95% 4.5
      63.0) and patients with MDR strains had a higher probability of need of re
      treatment (RR = 24.4, CI 95% 8.8-67.6), and of death (RR = 4.0, CI 95% 1.5-10.7).
      Additional variables were found to be associated with subsequent episodes of
      disease and mortality: Cocaine use, chronic disease, type of radiological
      lesions, HIV co-infection, non-compliance and treatment delay, as well as RFLP
      clustering. CONCLUSIONS: In this study, we observed that drug resistance showed a
      severe impact on the outcome and survival; drug-resistance was the most
      significant factor for these negative outcomes; DOTS may not be sufficient in
      areas where drug resistance is considerable, and patient follow-up for longer
      periods of time, as compared to evaluation at the end of treatment, provides
      additional information which is useful for prevention and control programs.

PMID- 11599479
TI  - [Scintigraphy with 99mTc-MIBI for assessment of tumor response to preoperative
      chemotherapy in patients with osteosarcoma].
AB  - In osteogenic sarcoma an increase in patient survival has been observed due to
      improvement of diagnostic and treatment methods. The objective of the
      investigation was to determine the usefulness of scintigraphy with 99mTc-MIBI in
      comparison to clinical revaluation, in order to assess tumor response (sarcoma)
      to chemotherapy previous to surgery. Patients with histopathological osteogenic
      sarcoma that received chemotherapy were included, clinical and scintigraphy
      response was assessed previous to the surgery. The gold standard for comparison
      was the degree necrosis histopathological analysis of the surgical specimen with
      measurement. Twelve patients met the inclusion criteria. A was observed a higher
      correlation between the 99mTc-MIBI and the histopathology. vs. clinical
      evaluation (0.89 vs. 0.59 respectively). Likewise the sensitivity (Se) and
      specificity (Sp) were superior (Se and Sp = 100% vs. Se 66.6% and Sp 75%) when
      therapeutically responses good and null were compared. We may conclude that
      scintigraphy with 99mTc-MIBI used to asses the response to presurgery
      chemotherapy in patients with osteogenic sarcoma, together with the clinical
      assessment, help the physician to make therapeutically decisions with more
      objectivity and certainly.

PMID- 11599480
TI  - Cardiac conduction disturbances in mixed connective tissue disease.
AB  - BACKGROUND: Myocardial involvement occurs in about 20% of patients with mixed
      connective tissue disease. The purpose of this study was to determine the
      prevalence of conduction disturbances, their association with other
      manifestations of the disease. OBJECTIVE: Determine the prevalence of cardiac
      conduction disturbances in patients with mixed connective tissue disease attended
      in an institute in Mexico City and their relation with other manifestations of
      the disease. METHODS: One hundred thirteen patients admitted to the Institute
      with a diagnosis of mixed connective tissue disease were divided into those with
      conduction disturbances (n = 23) and those without (n = 90). Over a mean follow
      up of 10.2 +/- 7.8 years, clinical course, treatment, duration of the disease,
      types of conduction disturbances and systemic alterations were examined. RESULTS:
      There was an overwhelming predominance of women in both groups. Conduction
      disturbances occurred in about 20% of the patients with mixed connective tissue
      disease and that was not possible to find significant differences in the outcome
      of them. As could be expected a significant difference between the two groups was
      QRS axis, related to anterior hemiblock, the most common conduction alteration
      observed. During the follow-up one patient death in-group A, but none in group B.
      CONCLUSION: Conduction disturbances were present in 20%; in agree with other
      authors in the literature. However, did not participate in the outcome of the
      disease.

PMID- 11599481
TI  - Induction of tumor necrosis factor-alpha by cefodizime in U-937 cells.
AB  - Cefodizime has modulating effects on the release of diverse cytokines. We
      determined the modulator activity of this antibiotic on the production of TNF in
      human monocytic U-937 cells. The measurement of TNF was carried out by ELISA test
      and by a L-929 cells-based citotoxic bioassay. The results showed that cefodizime
      alone induced the production of TNF on U-937 cells, however, the addition of LPS
      led to a decrease in the release of this cytokine (p < 0.05). On the other hand,
      the combination of cefodizime-PMA had a synergic effect (p < 0.05), while
      addition of LPS to this combination caused a decrease of TNF production (p <
      0.05). With these results we conclude that cefodizime modulates the production of
      TNF in U-937 cells, which is down regulated by the addition of LPS.

PMID- 11599482
TI  - [Pathogenic activity modulation of Escherichia coli TL+ toxin with an isolated
      protein of Giardia intestinalis and a synthetic peptide].
AB  - It is know that a protein from Giardia intestinalis works as a substrate for V.
      cholerae and Escherichia coli. The toxic activity of both activates protein G
      form intestinal mucosa with a pathogenic activity results. In the present study,
      the pathogenic activity of subunit A of Vibrio cholerae toxin (ADP
      ribosyltranferase) using isolated fragments from: Giardia intestinalis and a
      synthetic peptide were used as modulators in vivo. MATERIAL AND METHODS: Adult
      Neo Zealand males rabbits with ileal loop were prepared and different mixtures of
      heat labile enterotoxin obtained from Escherichia coli H10407 and ARF protein
      isolated by electrofocusing from Giardia intestinalis Portland I were inoculated
      in the loops. The toxin activity was evaluated by luminal liquid secretion and
      cyclic AMP concentration in tissues (each loop). RESULTS: ADP ribosyltranferase
      activity was modulated, due to a decreased of luminal secretion and cAMP in
      tissues. Such results were seen when synthetic peptide and subunit A from Vibrio
      cholerae were used. CONCLUSIONS: The ADP ribosyltranferase activity of heat
      labile Escherichia coli and Vibrio cholerae toxins were modified by in vitro and
      in vivo interaction with ARF protein, which modified pathogenic effect over
      rabbits intestinal epithelium.

PMID- 11599483
TI  - [Viral therapy of cancer].
AB  - In spite of the advances achieved in cancer therapeutics, conventional therapies
      still face problems such as toxicity to normal tissues and low efficacy in
      advanced phases of the disease. One of the most recent options, albeit
      experimental, is gene therapy. This strategy shows higher specificity than
      conventional therapies, but the low efficiency of gene transduction is a hurdle
      yet to be overcome, and the clinical trials have not shown the expected efficacy.
      Recently, oncolytic viruses have revived as an alternative in the field of cancer
      therapeutics. By virtue of the advances in virology and molecular biology
      techniques, the manipulation of viral genomes to attenuate their pathogenicity
      and the modification of their life cycle to allow tumor specific viral
      replication are now possible. At the moment, adenovirus and herpes simplex type 1
      mutants are the most commonly employed viruses. Recent clinical trials using
      these mutant viruses have shown safety and efficacy. Moreover, viral therapy has
      been combined with radiotherapy or chemotherapy demonstrating additive
      antineoplastic effects. In this manuscript, we review the biology behind this
      therapy, the obstacles, and the ongoing clinical trials.

PMID- 11599484
TI  - [Hepatic fibrosis].

PMID- 11599485
TI  - [New paradigms in the regulation of bone metabolism].
AB  - Although multiple hormones and cytokines regulate various aspects of osteoclast
      formation, the two final effectors, osteoprotegerin (OPG) and its ligand
      (OPGL/RANKL) have been recently identified. Since then, there have been important
      advances in the understanding of the molecular mechanisms that regulate the
      crosstalk between osteoblasts/stromal and hematopoietic osteoclast precursor
      cells. In this article, we describe the new concepts from the identification of
      OPG, a protein with potent osteoclastogenesis inhibitory activity, to the
      isolation of RANKL, a transmembrane ligand expressed on osteoblasts/stromal cells
      that bind to RANK, a transmembrane receptor on osteoclast cells and its
      precursors. The interaction between RANK and RANKL triggers a series of
      mechanisms that result in differentiation, maturation and activation of
      osteoclasts. OPG inhibits osteoclastogenesis binding to RANKL and blocks its
      interaction with RANK. Many hormones and cytokines, like PTH and IL-11, act
      inhibiting production of OPG and stimulating production of RANKL. Contrary to
      this, estrogens inhibit production of RANKL and RANKL-stimulated
      osteoclastogenesis. The knowledge of the RANK/RANKL/OPG system and the
      understanding of osteoclast differentiation and activation has had a great impact
      on the field of bone metabolism, with new possible treatment strategies for
      diseases characterized by excessive bone resorption.

PMID- 11599486
TI  - [Some facts about research at the Salvador Zubiran National Institute of Medical
      Science and Nutrition].

PMID- 11599487
TI  - [Syphilis at full term pregnancy in women from Cuernavaca, Mexico].

PMID- 11599488
TI  - Children with Parents or Siblings with Diabetes. Proceedings of the 9th
      International Beilinson-Schneider Symposium. Israel, 22-25 September 2000.

PMID- 11599489
TI  - Dennis Eisnach: a calm man in tough times.

PMID- 11599490
TI  - Health policy: ready, set, go! What's on the HIPAA horizon?

PMID- 11599491
TI  - Community health. Crossing the quality chasm: steps you can take.

PMID- 11599493
TI  - Proceedings of the 8th Asian-Pacific Congress of Nephrology. 26-30 March 2000.
      Taipei, Taiwan.

PMID- 11599492
TI  - Trustee workbook 3. Quality and value: overcoming barriers.

PMID- 11599494
TI  - Order of Excellence 2001 winners.

PMID- 11599496
TI  - Bibliography. Current world literature. Adult and pediatric gynecology.

PMID- 11599497
TI  - Bibliography. Current world literature. Urogynecology.

PMID- 11599498
TI  - Statistical issues in biopharmaceutical environments: towards the next
      millennium. Proceedings of a conference. 28-30 July 1999.

PMID- 11599500
TI  - Laboratory products and services guides.

PMID- 11599499
TI  - ARDF response to USDA inspections and the inclusion of rats, mice and birds in
      the AWA.

PMID- 11599501
TI  - [Richard Freiherr von Krafft-Ebing (1840-1903); comments on the cover portrait].

PMID- 11599502
TI  - Current readings in nuclear medicine.

PMID- 11599503
TI  - Elucidating penetration pathways into the hair fiber using novel microscopic
      techniques.
AB  - Much controversy exists regarding the route of penetration of molecules into hair
      fibers. In brief, there are two schools of thought. The first argument is that
      molecules enter the hair fiber via the cell membrane complex (cmc) of the cuticle
      and then diffuse throughout the cortex via both the intercellular cement and the
      bulk of individual cortical cells. The second approach concludes that entry to
      the fiber is via the endocuticle and other non-keratinous parts of the fiber. In
      the latter case the cmc is definitely not considered to have a role in the
      penetration of molecules into the fiber. The tools available for studying
      penetration into the fiber, e.g., light and electron microscopy, mean that it is
      usually only possible to extract static information from a dynamic process.
      Similarly, great care is needed in the interpretation of images produced by the
      various techniques. Where a molecule is seen to end up does not always indicate
      how it got there! In these studies I have used novel derivations of conventional
      electron microscopic techniques, combined with early photographic chemistry, to
      elucidate further the pathways of penetration into the hair fiber. From these
      studies one can conclude that both arguments describing penetration into the
      fiber are complementary, valid, and highly relevant. The techniques allow one to
      visualize material within the cell membrane complex of the cuticle. In addition,
      these studies show that the high-sulphur proteins of the cuticle, usually
      considered as highly cross-linked and inaccessible, are easily penetrated.
      Therefore, all of the structures within a hair fiber should be considered as
      penetration routes into the hair fiber for the delivery of industrial and
      cosmetic materials, even though they may not form continuous pathways throughout
      the hair. The hair should be viewed as a structure composed of a number of
      compartments of differing capacity, chemistry, and accessibility, rather than as
      continuous pathways from the surface to the center of the fiber.

PMID- 11599504
TI  - Things are looking up.

PMID- 11599505
TI  - Choroidal detachment following extracapsular cataract extraction in a patient
      treated with latanoprost.

PMID- 11599506
TI  - Beta-hydroxy-beta-methylbutyrate (HMB) supplementation does not affect changes in
      strength or body composition during resistance training in trained men.
AB  - This investigation evaluated the effects of oral beta-hydroxy-beta-methylbutyrate
      (HMB) supplementation on training responses in resistance-trained male athletes
      who were randomly administered HMB in standard encapsulation (SH), HMB in time
      release capsule (TRH), or placebo (P) in a double-blind fashion. Subjects
      ingested 3 g x day(-1) of HMB or placebo for 6 weeks. Tests were conducted pre
      supplementation and following 3 and 6 weeks of supplementation. The testing
      battery assessed body mass, body composition (using dual energy x-ray
      absorptiometry), and 3-repetition maximum isoinertial strength, plus biochemical
      parameters, including markers of muscle damage and muscle protein turnover. While
      the training and dietary intervention of the investigation resulted in
      significant strength gains (p < .001) and an increase in total lean mass (p =
      .01), HMB administration had no influence on these variables. Likewise,
      biochemical markers of muscle protein turnover and muscle damage were also
      unaffected by HMB supplementation. The data indicate that 6 weeks of HMB
      supplementation in either SH or TRH form does not influence changes in strength
      and body composition in response to resistance training in strength-trained
      athletes.

PMID- 11599507
TI  - An interview with Dr. Gary Green about supplements and doping problems from an
      NCAA perspective. Interview by Louise Burke.

PMID- 11599508
TI  - ILSI: no attempt to influence.

PMID- 11599509
TI  - Taking money from the drinks industry does not necessarily set up a conflict.

PMID- 11599510
TI  - Brief interventions for substance use disorders other than alcohol.

PMID- 11599511
TI  - Methodological issues attached to the alcohol Stroop paradigm: a rejoinder to
      Cox, Pothos, Johnsen and Laberg.

PMID- 11599512
TI  - Cost-effectiveness estimates for buprenorphine should factor in crime.

PMID- 11599513
TI  - Cost-effectiveness of buprenorphine maintenance versus methadone maintenance.

PMID- 11599514
TI  - Opioid maintenance: the politics matter.

PMID- 11599515
TI  - Comment of Bischof et al's "Factors influencing remission without formal help
      from alcohol dependence in a representative population sample.

PMID- 11599516
TI  - Maturing out?

PMID- 11599517
TI  - Ecstasy: the key to understanding problem use lies in understanding the
      users'social networks.

PMID- 11599518
TI  - Foot and mouth disease: a revised policy is required.

PMID- 11599519
TI  - Detection of cytomegalovirus DNA in human specimens by LightCycler PCR: melting
      point analysis is mandatory to detect virus strains with point mutations in the
      target sequence of the hybridization probes.

PMID- 11599520
TI  - Prediction of enterococcal imipenem susceptibility using ampicillin or penicillin
      MICs: more evidence for a class concept.

PMID- 11599521
TI  - Whole-blood hepatitis C virus RNA extraction methods.

PMID- 11599522
TI  - Genetic mutations occur gradually in in vivo populations of Mycobacterium
      tuberculosis bacteria.

PMID- 11599523
TI  - Tuberculosis transmission in Botswana.

PMID- 11599524
TI  - Use of glucosamine and chondroitin sulfate in the management of osteoarthritis.

PMID- 11599525
TI  - Acute renal failure secondary to hydroxyethylstarch administration in a surgical
      patient.

PMID- 11599526
TI  - A case of Campylobacter fetus endocarditis of the tricuspid valve unaccompanied
      by fever.

PMID- 11599527
TI  - Non-sustained ventricular tachycardia due to low-dose orphenadrine.

PMID- 11599528
TI  - Sjogren's syndrome and vitiligo in a woman with posttransfusion microchimerism.

PMID- 11599529
TI  - A unique area of the homonculus: the topography of the primary somatosensory
      cortex in humans following posterior scalp and shoulder stimulation.
AB  - We recorded somatosensory evoked magnetic field (SEF) to investigate the
      differentiation in the receptive area for the face, lower part of the posterior
      scalp (mastoid) and shoulder, which occupy an unique area in the homunculus. We
      analyzed the location of the equivalent current dipole (ECD) of SEF following
      electrical stimulation of the skin at the face, mastoid and shoulder in 20 normal
      subjects. Three deflections (1M, 2M and 3M) were obtained within 50 ms of the
      stimulation in 16 of 20 subjects. The peak latency of the 1M and 2M was not
      significantly different at any stimulus sites. The amplitude of the 1M was
      significantly larger following the face than mastoid stimulation (p<0.05). The 16
      subjects were classified according to the locations of the ECD on stimulation of
      the mastoid: close to that for shoulder stimulation, but significantly (p<0.05)
      more superior and medial to that following the face stimulation (Type 1, eleven
      subjects); close to that for face stimulation, but significantly (P<0.05) more
      inferior and lateral to that following the shoulder stimulation (Type 2, five
      subjects). The site of the receptive area for the posterior scalp shows
      interindividual variation, possibly due to anatomical differences.

PMID- 11599530
TI  - P300 and neuropsychological tests as measures of aging: scalp topography and
      cognitive changes.
AB  - The rationale for the present study was to investigate several aspects of P300
      topography in relation to aging and neuropsychological measures. We administered
      an auditory oddball ERP task to 72 participants aged 21.8 to 94.7 years, 36 males
      and 36 females, in addition to the Wechsler Abbreviated Scales of Intelligence
      (WASI) and digit span from the Wechsler Adult Intelligence Scales--Revised (WAIS
      R). The relationship between age and P300 latency and amplitude at different
      electrodes was investigated, as well as the changes in the correlational pattern
      between P300 latency and amplitude with increasing age. A formal test of
      curvilinear relationships for P300 latency/amplitude and age was performed.
      Principal component factor analyses were performed for P300 latency and amplitude
      separately in order to check for possible superordinate structures in the
      distribution of the electrical activity measured at the scalp. In addition, each
      of the electrodes and each of the factors were correlated with the different
      neuropsychological measures, and the contribution of age to the observed
      relationships is discussed. The main conclusion drawn is that the activity
      generated from different brain areas change at different rates with age. While
      the posterior area shows a clear reduction of P300 amplitude and a delay of P300
      latency with age, the amplitude does not decrease at the same rate in the fronto
      central areas, and there is at the same time a marked hemispheric asymmetry in
      the age dependent change of activation. Based on our data, it may be concluded
      that a curvilinear expression generally does not explain the aging effect on the
      ERP component P300. Correlations between neuropsychological measures and P300
      did, as expected, vary with area of activation, and the strongest correlations
      were generally found between matrices, block design and digit span, and the
      midline and left fronto-temporal electrodes. These relationships were in turn
      mediated by age. Implications of the findings are discussed.

PMID- 11599531
TI  - Grapheme monitoring in picture naming: an electrophysiological study of language
      production.
AB  - Electrocortical correlates of language production were examined in two picture
      naming tasks that involved grapheme monitoring. In both tasks subjects (N=12) had
      to detect target letters in picture names, the target letter being positioned
      either at the beginning or at the end of the picture name. Between tasks, the
      target letter was shown either before (target-picture, TP) or after (picture
      target, PT) the presentation of the object pictures. In both tasks, subjects
      responded faster, whenever the target letter appeared at the beginning of the
      picture name than at its end. The EEG, recorded from 64 electrodes, was analyzed
      in the signal and in the source space (using the Minimum Norm estimate).
      Differences in the event-related potential (ERP) following the second stimulus
      became evident earlier in the PT (at 320 ms) than the TP (456 ms) task. This
      onset of diverging ERPs was called the "point of divergence" (POD). The ERP
      following the POD was characterized by a positive deflection in the "begin"
      condition in both tasks. In the "end" condition, the sources of brain activity
      were focused over the left hemisphere in the TP, while a bilateral distribution
      characterized the PT task. Performance and electrocortical indices support the
      hypothesis of serial "left-to-right" processing of a representation of the
      picture name. The left-hemispheric activity focus in the TP task is assumed to
      indicate the encoding of the picture name, while frontal symmetrical activity in
      the PT task might indicate the involvement of working memory processes.

PMID- 11599532
TI  - Development and characterization of an automatic technique for the alignment of
      fMRI time series.
AB  - An automatic technique for the registration of fMRI time series has been
      developed, implemented and tested. The method assumes the human brain to be a
      rigid body and computes a head coordinate system on the basis of three reference
      points that lies on the directions corresponding to two of the principal axes of
      the volume at the intersections with the head boundary. Such directions are found
      computing the eigenvectors of the symmetric inertia matrix of the image. The
      inertia components were extracted weighting pixels' coordinates with their
      intensity values. The three reference points were found in the same position,
      relative to the head, in both the test and the reference images. The technique
      has been tested using T2*-weighted Magnetic Resonance (MR) images in which known
      rigid body transformations have been applied. The results obtained indicate that
      the method offers subvoxel accuracy in correcting misalignment among time points
      in fMRI time series.

PMID- 11599533
TI  - MRI prior computation and parallel tempering algorithm: a probabilistic
      resolution of the MEG/EEG inverse problem.
AB  - Since the MEG inverse problem is ill-posed and admits many possible solutions, it
      is not possible to give it a single "true" answer. Therefore, we propose here to
      use a specific probabilistic algorithm to map the full probability distribution
      of the MEG sources with Markov Chain Monte Carlo methods. Using a Bayesian
      approach, the probability of the MEG solutions is expressed as the product of the
      likelihood by the prior probability. To compute the prior and constrain the MEG
      inverse problem resolution, MRI data are also acquired and automatically
      processed to determine the brain position and volume. We then use Parallel
      Tempering algorithm to estimate the full posterior probability and determine the
      likely solutions of the inverse problem. We illustrate the method with results
      obtained from the analysis of somatosensory data. This illustrates both the MRI
      processing for the prior computation, and how the knowledge of the full posterior
      probability distribution can be used to estimate the position of the sources, as
      well as their likely extension.

PMID- 11599535
TI  - A Nobel Prize for sustainability, perhaps?

PMID- 11599534
TI  - Signal analysis of auditory evoked cortical fields in fetal
      magnetoencephalography.
AB  - Magnetoencephalography (MEG) using auditory evoked cortical fields (AEF) is an
      absolutely non-invasive method of passive measurement which utilizes magnetic
      fields caused by specific cortical activity. By applying the exceptionally
      sensitive SQUID technology to record these fields of dipolar configuration
      produced by the fetal brain, MEG as an investigational tool could provide new
      insights into the development of the human brain in utero. The major constraint
      to this application is a very low signal-to-noise ratio (SNR) that has to be
      attributed to a variety of factors including the magnetic signals generated by
      the fetal and maternal hearts which inevitably obscure a straightforward signal
      analysis. By applying a new algorithm of specific heart artefact reduction based
      on the relative regularity of the heart signals, we were able to increase the
      chance of extracting a fetal AEF from the raw data by the means of averaging
      techniques and principle component analysis. Results from 27 pregnant, healthy
      women (third trimester of their uncomplicated pregnancy) indicate an improved
      detection rate and the reproducibility of the fetal MEG. We evaluate and discuss
      a-priori criteria for signal analyses which will enable us to systematically
      analyze additional limiting factors, to further enhance the efficiency of this
      method and to promote the assessment of its possible clinical value in the
      future.

PMID- 11599536
TI  - Candidate number 1: instant runoff voting.

PMID- 11599537
TI  - Candidate number 2: proxy representation.

PMID- 11599538
TI  - SciTecPac was science's first watchdog.

PMID- 11599539
TI  - Evaluation of potential bloodborne pathogen exposures among body piercers.

PMID- 11599540
TI  - XML: sharing occupational health data in the information age.

PMID- 11599541
TI  - Control of wood dust from automated routers. National Institute for Occupational
      Safety and Health.

PMID- 11599542
TI  - Re: Article by Dale J. Stephenson and Dean R. Lillquist entitled "The effects of
      temperature and pressure on air-borne exposure concentrations when performing
      compliance evaluations using ACGIH TLVs and OSHA PELs".

PMID- 11599543
TI  - Electron microscopy study of refractory ceramic fibers.
AB  - In epidemiological studies designed to identify potential health risks of
      exposures to synthetic vitreous fibers, the characterization of airborne fiber
      dimensions may be essential for assessing mechanisms of fiber toxicity. Toward
      this end, air sampling was conducted as part of an industry-wide study of workers
      potentially exposed to airborne fibrous dusts during the manufacture of
      refractory ceramic fibers (RCF) and RCF products. Analyses of a subset of samples
      obtained on the sample filter as well as on the conductive sampling cowl were
      performed using both scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM) to characterize dimensions of airborne fibers. Comparison was
      made of bivariate fiber size distributions (length and diameter) from air samples
      analyzed by SEM and by TEM techniques. Results of the analyses indicate that RCF
      size distributions include fibers small enough in diameter (< 0.25 microm) to be
      unresolved by SEM. However, longer fibers (> 60 microm) may go undetected by TEM,
      as evidenced by the proportion of fibers in this category for TEM and SEM
      analyses (1% and 5%, respectively). Limitations of the microscopic techniques and
      differences in fiber-sizing rules for each method are believed to have
      contributed to the variation among fiber-sizing results. It was concluded from
      these data that further attempts to characterize RCF exposure in manufacturing
      and related operations should include analysis by TEM and SEM, since the smallest
      diameter fibers are not resolved with SEM and the fibers of longer length are not
      sized by TEM.

PMID- 11599544
TI  - Perceptions of indoor air quality associated with ventilation system types in
      elementary schools.
AB  - With the increased utilization of school buildings on a year-round basis, school
      indoor air quality has become a national concern. The purpose of this study was
      to evaluate possible associations between ventilation system type and occupant
      perception of indoor air quality. Staff (n = 403) from 12 schools completed a
      self-administered questionnaire. Carbon dioxide (CO2) levels, air exchange rates,
      and particle counts were also measured for each school. Schools with unit
      ventilator (UV) systems had the lowest mean CO2 level at 637 ppm, followed by the
      variable air volume (VAV) systems with 664 ppm, and constant volume (CV) systems
      with a mean of 703 ppm. Schools with UV systems had the lowest mean air exchange
      rate at 2.67 air changes per hour (ACH), followed by the VAV system type at 2.80
      ACH and the CV system type at 4.61 ACH. Indoor versus outdoor particle ratios
      were calculated for each ventilation system type. Particles with aerodynamic
      diameters ranging from 0.1-1.0 microm had a geometric mean ratio ranging from
      0.38 to 0.68; particles with aerodynamic diameters ranging from 1-3 microm had
      ratios ranging from 1.39 to 5.47, and particles with aerodynamic diameters
      greater than 3 microm had ratios ranging from 3.20 to 14.76. Schools using VAV
      systems had a significantly lower prevalence of red and watery eyes while schools
      with UV systems had an elevated prevalence of nasal congestion, sore throat,
      headache, and dustiness complaints. This increased prevalence of complaints in
      buildings with UV systems may be due to the increased particulate levels.

PMID- 11599545
TI  - MCPA permeation through protective gloves.
AB  - Permeation of 4-chloro-2-methylphenoxyacetic acid (MCPA) in commercial herbicide
      formulations through common protective glove types was evaluated to aid in the
      selection of appropriate skin protection. The ASTM test method F739-91 was used
      to measure the permeation of two undiluted formulations, one containing a salt,
      and the other an ester form of MCPA. The four glove types tested were natural
      rubber, neoprene 73, nitrile 37-145, and Viton-coated chloroprene. Triplicate
      tests of each combination of formulation and glove material were conducted.
      Permeation cells with a 0.01 M sodium hydroxide collection medium were used for
      the experiments. Aliquots of the collection medium were withdrawn at regular
      intervals and acidified, and quantification of the free acid was achieved using
      HPLC-UV (230 nm). There was no appreciable permeation of the salt formulation
      over a 24-hour test period. For the ester formulation, the following mean steady
      state permeation rate (microg x cm(-2) min(-1)) and mean lag time (hours),
      respectively, were measured: Viton (0.06, 17.8), natural rubber (0.08, 15.4),
      neoprene 73 (0.21, 15.1), and nitrile (0.04, 24.2). Permeation was associated
      with significant swelling, averaging a nearly 30 percent increase from the pre
      immersion thickness. All four glove types provide adequate protection against
      permeation by the salt formulation and at least eight-hour protection against the
      ester formulation. Given the greater permeation of the ester formulation, the
      salt formulation of MCPA herbicide should be used whenever possible.

PMID- 11599546
TI  - Characterizing formaldehyde emission rates in a gross anatomy laboratory.
AB  - The evaporation of formaldehyde from cadavers in gross anatomy laboratories can
      produce high exposures among students and instructors. To understand the system
      that produces exposures and to plan for implementing control options, the
      generation of formaldehyde vapors must be characterized. A gross anatomy
      laboratory with 47 dissecting tables was studied during 15 lab sessions over a
      period of 16 weeks. Area concentrations were measured using National Institute of
      Occupational Safety and Health (NIOSH) method 3500. Average daily area
      concentrations in the laboratory ranged from 0.635 to 1.82 mg/m3. The ventilation
      was characterized on three separate days. The laboratory had a general
      ventilation rate of 9.8 air changes per hour. There was no local exhaust
      ventilation. The concentration measurements were used in a mass balance model
      along with ventilation rates to determine formaldehyde emission rates. The daily
      average formaldehyde emission rate from all sources in the laboratory ranged from
      95.2-274 mg/min, with an average of 148 mg/min over the course of the study. This
      total emission rate was used along with the number of dissecting tables to
      develop an emission factor of 3.15 mg/min per table. The emission factor is a
      generalizable tool that can be used in laboratories of various sizes to predict
      emission rates and develop control strategies. This emission factor is applicable
      where the cadavers are prepared with similar embalming fluid consisting of
      approximately 10 percent formaldehyde.

PMID- 11599547
TI  - A pilot study to rate determinants of exposure from videotaped work activities of
      farmers' use of pesticides.
AB  - Industrial hygienists often observe workers to determine who should be measured
      based on a predicted exposure level. Such evaluations are usually based on real
      time observation, yet surprisingly little research has been conducted on what
      determinants of exposure industrial hygienists use to rank workers and whether
      the ranking is accurate. Accuracy of the ranking may also be affected by the
      observation process, which is limited when conditions in the workers' immediate
      environment are rapidly changing. An alternative to real-time observation is
      videotaping workers and evaluating the tapes at a later date. A pilot study was
      conducted using previously collected data to determine if workers could be ranked
      by exposure level utilizing a scoring system to rate videotaped work practices.
      Six farmers had been videotaped and their dermal exposures measured as they
      applied insecticide to hogs. In this study, scores were developed to rate the
      farmers' working conditions by exposure level. Two types of determinants were
      used to describe exposure: touching and work practices. Touching included the
      number of times parts of the body had contact with surfaces possibly contaminated
      with insecticide. Work practices included the types of clothing and protective
      equipment worn as well as specific practices used by the farmer (e.g.,
      application method). Two raters conducted independent assessments of the
      videotape using the same criteria. One rater reviewed the tape twice. Agreement
      between the raters for the "touching" score was weak (intra-class coefficient
      (ICC) = 0.28), but there was excellent agreement between the two raters (ICC =
      0.92) for overall quality of work practices. As expected, a greater number of
      touches was moderately correlated with an increase in total exposure (rs = 0.60)
      and there was a weak inverse relationship between protective work practices and
      the exposure under the clothing (rs = -0.26). All other relationships with
      exposure level were contrary to what was expected. Since videotapes provide the
      industrial hygienist with a record of work events and can capture details that
      might otherwise be missed or not considered they may play a useful role in
      exposure assessment, especially if carefully developed procedures are followed to
      overcome the limitations found by this pilot study.

PMID- 11599548
TI  - A modified protocol for quantitative fit testing using the PortaCount.
AB  - A modified quantitative fit testing method has been developed for testing half
      masks using the TSI PortaCount respirator fit tester. This approach focuses on
      shortening the time for each exercise during fit testing; however, the shortened
      protocol is applied only to the very good-fitting masks. For marginal-fitting
      masks, the testing is carried out according to the full Occupational Safety and
      Health Administration (OSHA) respiratory protection standard (29CFR1910.134).(1)
      The shortened protocol (currently not approved by OSHA) still uses all the
      exercises required by the OSHA standard but for a shorter time (30 seconds [s]
      for each exercise instead of the usual 60 s). How good the fit has to be to
      qualify for a shortened exercise is determined by the statistical analysis of a
      large data set containing pass and fail fit-test data. The statistical analysis
      involves calculating the sensitivity and specificity of the pass and failed fit
      tests on half masks. From this analysis, a multiplication factor (K) to the OSHA
      pass/fail criterion was developed. For a respirator to undergo the shortened
      protocol, the fit factor obtained during any exercise must be K times the OSHA
      pass/fail criterion of 100 for half masks. Hence, this approach is more
      conservative than fit testing protocols that involve shortened exercises
      regardless of the fit. Nevertheless, this approach still saves time without
      compromising the accuracy of the fit test expressed in terms of sensitivity and
      specificity. For the existing data, 85 percent of the fit tests would have been
      performed according to the faster test protocol while only 15 percent of the
      tests would have been tested according to the full-length OSHA test protocol.

PMID- 11599550
TI  - Magnesium deficiency-induced anorexia in hyperphagic obese Zucker rats.
AB  - In clinical practice diabetes mellitus is the most significant cause of
      hypomagnesemia and Mg depletion. The obese Zucker rat approaches non-insulin
      dependent type II diabetes; lean Zucker rats being suitable controls. Using this
      disease model the influence of dietary Mg deficiency was studied: animals
      received a diet providing only approximately 25 per cent of the Mg requirement;
      controls received drinking water fortified with Mg (16 mmol/L). During 125 days
      ad libitum feeding, Mg-deficient obese rats consumed nearly 50 per cent less feed
      pellets and gained 50 per cent less body weight than their obese counterparts.
      This effect was not fully reversible indicating Mg depletion. Blood glucose
      reflected food consumption, no glucosuria was detectable using test strips. In
      the heart muscle Mg was decreased and Ca increased in Mg-deficient rats
      indicating increased cardiac risk. When the rats were pair fed with lean Mg
      deficient controls the development of obesity was prevented. Despite pronounced
      Mg deficiency blood glucose remained unaffected and no glucosuria was detectable.
      In future experiments the production of marginal Mg deficiency not inducing
      anorexia should be applied to study the pathogenetic role of Mg depletion in
      obese Zucker rats.

PMID- 11599549
TI  - Mechanisms of action of the anti-atherogenic effect of magnesium: lessons from a
      mouse model.
AB  - Magnesium (Mg) fortification of drinking water succeeded in inhibition of
      atherogenesis development in a transgenic model of atherosclerosis-prone mice fed
      a high-cholesterol content diet. In order to delineate possible mechanisms of
      action of the anti-atherogenic effect of Mg, the involvement of LDL oxidation was
      studied. We determined the susceptibility of LDL to Cu+2 oxidation, anti-oxidized
      LDL antibody levels, and liver content of retinol and retinyl-palmitate. In order
      to study another possible mechanism we tested platelets interaction with
      extracellular matrix in both male and female mice with or without Mg
      fortification of drinking water. No difference was found in susceptibility of LDL
      to undergo oxidation. Female mice that received Mg had decreased anti-oxidized
      LDL antibody levels compared with control female mice, while there was no
      significant difference among male groups. On the other hand, only in the male
      group with Mg was a higher content of retinol and retinyl-palmitate found in the
      livers. Platelets coverage area on extracellular matrix was similar between
      groups. These results suggest that Mg might affect LDL oxidation, and thus
      atherogenesis.

PMID- 11599551
TI  - The effect of oral aspartame administration on the balance of magnesium in the
      rat.
AB  - The aim of the present work was to determine the effect of aspartame
      administration on the excretion of magnesium and its distribution in the various
      rat tissues and organs. The present results have shown that aspartame
      administration influences the balance of magnesium in the organism, since in some
      organs and tissues (heart, lungs, kidneys, adrenals, jejunum, hair and blood) it
      is accumulated, while other organs (liver and testes) are deprived of it.
      Aspartame administration also affects the excretion of magnesium from the
      organism, since it decreases the concentration of magnesium in both urine and
      feces.

PMID- 11599552
TI  - The effect of magnesium deficiency on volatile anaesthetic requirement in the
      rat: the role of central noradrenergic neuronal activity.
AB  - Volatile anaesthetic minimum alveolar concentration (MAC, a measure of
      anaesthetic requirement) increased in a time-dependent manner in rats fed a Mg2+
      deficient diet. MAC values in hypomagnesemic rats were 22-30 per cent greater
      than those in age-matched controls at 12 and 17 days after starting the diet (p <
      0.01). Noradrenergic neuronal activity, as assessed from the ratio of the
      concentration of 3,4-dihydroxyphenylethylene-glycol (DHPG) to that of
      norepinephrine (NE), decreased in the brain stem and cerebrum-cerebellum in
      hypomagnesemic rats owing to an increase in NE concentration in both regions of
      the brain (p < 0.025). We conclude that prolonged hypomagnesemia (> or = 12 days)
      increases volatile anaesthetic MAC in the rat. The concomitant decrease in the
      ratio of DHPG/NE suggests that this increase in MAC cannot be attributed to an
      increase in noradrenergic neuronal activity in brain.

PMID- 11599553
TI  - Characteristics of improved NOVA magnesium ion-selective electrode: changes of
      ionized magnesium values and reference interval in healthy children.
AB  - Following the report of interference between the thiocyanate ion (SCN-) and
      NOVA's previous ion-selective electrode (ISE) for ionized magnesium (iMg2+), NOVA
      has developed a new ISE which eliminates the effect of SCN-. Two hundred and
      sixty healthy children were divided into two groups; those who had presented when
      using NOVA's previous ISE (group A; n = 160) and those using NOVA's new ISE
      (group B; n = 100). The mean iMg2+ value and the mean iMg2+ percent fraction
      (iMg2+/serum Mg) were significantly higher in group B than in group A (0.59 +/-
      0.03 vs 0.54 +/- 0.03 mmol/L for iMg2+; p < 0.001 and 64.8 +/- 3.1 vs 58.2 +/-
      4.1 per cent for iMg2+ percent fraction; p < 0.001). The mean serum SCN- level
      was 0.023 +/- 0.008 mmol/L in group A (n = 8) and 0.0.21 +/- 0.007 mmol/L in
      group B (n = 12), and was not significantly different between the two groups. The
      suspected change of iMg2+ value interfered by SCN- was 0.037 mmol/L in group A.
      The difference of iMg2+ percent fraction between two groups was higher at high
      serum magnesium (SMg) levels. The reference interval of iMg2+ was 0.56-0.62 mmo/L
      in healthy children with the NOVA's new ISE, and was constant irrespective of
      growth. The NOVA's previous iMg2+ ISE may be interfered with mainly by SCN-. The
      newly designed ISE eliminated these effects especially at higher SMg levels.

PMID- 11599554
TI  - Dietary intakes of Mg, Ca and P with whole-day food rations from Cracovie, Lodz,
      Olsztyn and Poznan, Poland.
AB  - Magnesium, calcium and phosphorus have been determined in whole-day food rations
      collected during three consecutive days in winters of 1993/4, 1995 and 1996 in
      hospital canteens in Krakow, Lodz, Olsztyn and Poznan, Poland. Portions of food
      for one person were collected. In 1998 whole-day food rations of seven students
      (five consecutive days) and, in 1999, of eight adults (three consecutive days)
      were also prepared for Mg, Ca and P determination. Mg and Ca were determined by
      ASA and P by colorimetric method. The diets collected at hospital canteens were
      deficient in magnesium but not in calcium. Duplicate diets did not supply enough
      magnesium and calcium. All the whole-day food rations contained 2-4-fold excess
      of phosphorus. Such a composition of macroelements in food can pose a threat to
      human health.

PMID- 11599555
TI  - New data on the mechanisms of hypermagnesuria in type I diabetes mellitus.
AB  - It has been known for long that renal Mg excretion is increased in patients with
      type I diabetes mellitus, and that these patients have a Mg deficit. It can be
      hypothesized, that this deficit might be related to the development of late
      complications in the diabetic. In recent years it has been shown that the
      increased renal Mg excretion in patients with type I diabetes is due primarily to
      an elevated plasma glucose concentration. An increase in plasma glucose
      concentration from 5 to 12 mmol/l more than doubles renal Mg excretion, if
      everything else is kept constant. Hyperinsulinism may also contribute to the
      increased renal Mg excretion. However, since improved metabolic control in
      patients with type I diabetes reduces the renal Mg loss despite an increase in
      insulin dosage, hyperinsulinism is probably of minor importance in the aetiology
      of hypermagnesuria in patients with type I diabetes mellitus, compared with the
      effect of hyperglyeaemia.

PMID- 11599556
TI  - Serum magnesium and calcium in patients with dorsalgias.
AB  - Serum magnesium and calcium was examined in 70 patients with chronic dorsalgias.
      Values of calcium were stabilized, but values of magnesium were unstable and
      exceeded the 2SD lines, being more often over than under these lines. Lability of
      serum magnesium levels is considered a secondary consequence, caused by the
      stress of pain. These symptoms may be alleviated by Mg administration, by local
      application of Mg through transdermic iontophoresis or sonophoresis, or by
      hydropathy of the paravertebral muscles.

PMID- 11599557
TI  - A triple-risk model for the sudden infant death syndrome (SIDS) and the apparent
      life-threatening episode (ALTE): the stressed magnesium deficient weanling rat.
AB  - A triple risk model for the sudden infant death syndrome (SIDS) as described by
      Filiano and Kinney involves the intersection of three risks: (1) a vulnerable
      infant, (2) a critical developmental period in homeostatic control, and (3) an
      exogenous stressor(s). The triple risk model aptly describes the dynamics of an
      animal model for SIDS: (1) a vulnerable animal that is young and magnesium
      deficient: (2) a critical developmental period revealed by hyperirritability,
      labile cardiovascular and respiratory control; and (3) an exogenous stressor such
      as soft, high-pitched noise; motion or handling; or a chill. Together these three
      risks may trigger a shock-like episode of apnea, unconsciousness and bradycardia.
      The lung is the shock organ. An animal that dies quietly or after physical
      activity following the episode, models SIDS. However, if the shock-like episode
      resolves spontaneously or after resuscitation, the survivor is a model for an
      apparent life-threatening episode (ALTE). If, while still in the critical
      developmental period the ALTE survivor is stressed again, there is a risk for a
      recurrent episode, with the final outcome still unpredictable but with increasing
      risk for SIDS with multiple recurrences. The purpose of this communication is to
      present an illustrated review of the magnesium deficient weanling rat as an
      animal model for SIDS/ALTE, showing pertinent physical, electrocardiographic and
      pathological features. In the weanling rat, magnesium deficiency appears to be
      the single common pathway upon which multiple stressors may impinge to produce
      sudden death during the relatively brief critical developmental period, while
      magnesium supplements may protect the animal. If significant magnesium deficiency
      is subsequently diagnosed in a properly controlled study of human SIDS tissue, it
      is likely that a high proportion of SIDS deaths could be prevented by simple oral
      magnesium supplementation to infants during the first critical weeks and months
      of life.

PMID- 11599558
TI  - A genomics approach to the chaperone network of Arabidopsis thaliana.

PMID- 11599559
TI  - Arabidopsis and the heat stress transcription factor world: how many heat stress
      transcription factors do we need?
AB  - Sequencing of the Arabidopsis genome revealed a unique complexity of the plant
      heat stress transcription factor (Hsf) family. By structural characteristics and
      phylogenetic comparison, the 21 representatives are assigned to 3 classes and 14
      groups. Particularly striking is the finding of a new class of Hsfs (AtHsfC1)
      closely related to Hsf1 from rice and to Hsfs identified from frequently found
      expressed sequence tags of tomato, potato, barley, and soybean. Evidently, this
      new type of Hsf is well expressed in different plant tissues. Besides the DNA
      binding and oligomerization domains (HR-A/B region), we identified other
      functional modules of Arabidopsis Hsfs by sequence comparison with the well
      characterized tomato Hsfs. These are putative motifs for nuclear import and
      export and transcriptional activation (AHA motifs). There is intriguing
      flexibility of size and sequence in certain parts of the otherwise strongly
      conserved N-terminal half of these Hsfs. We have speculated about possible exon
      intron borders in this region in the ancient precursor gene of plant Hsfs,
      similar to the exon-intron structure of the present mammalian Hsf-encoding genes.

PMID- 11599560
TI  - Arabidopsis thaliana type I and II chaperonins.
AB  - An examination of the Arabidopsis thaliana genome sequence led to the
      identification of 29 predicted genes with the potential to encode members of the
      chaperonin family of chaperones (CPN60 and CCT), their associated cochaperonins,
      and the cytoplasmic chaperonin cofactor prefoldin. These comprise the first
      complete set of plant chaperonin protein sequences and indicate that the CPN
      family is more diverse than previously described. In addition to surprising
      sequence diversity within CPN subclasses, the genomic data also suggest the
      existence of previously undescribed family members, including a 10-kDa
      chloroplast cochaperonin. Consideration of the sequence data described in this
      review prompts questions about the complexities of plant CPN systems and the
      evolutionary relationships and functions of the component proteins, most of which
      have not been studied experimentally.

PMID- 11599561
TI  - Genomic analysis of the Hsp70 superfamily in Arabidopsis thaliana.
AB  - The Arabidopsis genome contains at least 18 genes encoding members of the 70
      kilodalton heat shock protein (Hsp70) family, 14 in the DnaK subfamily and 4 in
      the Hsp110/SSE subfamily. While the Hsp70s are highly conserved, a phylogenetic
      analysis including all members of this family in Arabidopsis and in yeast
      indicates the homology of Hsp70s in the subgroups, such as those predicted to
      localize in the same subcellular compartment and those similar to the mammalian
      Hsp110 and Grp170. Gene structure and genome organization suggest duplication in
      the origin of some genes. The Arabidopsis hsp70s exhibit distinct expression
      profiles; representative genes of the subgroups are expressed at relatively high
      levels during specific developmental stages and under thermal stress.

PMID- 11599562
TI  - The J-domain proteins of Arabidopsis thaliana: an unexpectedly large and diverse
      family of chaperones.
AB  - A total of 89 J-domain proteins were identified in the genome of the model
      flowering plant Arabidopsis thaliana. The deduced amino acid sequences of the J
      domain proteins were analyzed for an assortment of structural features and
      motifs. Based on the results of sequence comparisons and structure and function
      predictions, 51 distinct families were identified. The families ranged in size
      from 1 to 6 members. Subcellular localizations of the A thaliana J-domain
      proteins were predicted; species were found in both the soluble and membrane
      compartments of all cellular organelles. Based on digital Northern analysis, the
      J-domain proteins could be separated into groups of low, medium, and moderate
      expression levels. This genomics-based analysis of the A thaliana J-domain
      proteins establishes a framework for detailed studies of biological function and
      specificity. It additionally provides a comprehensive basis for evolutionary
      comparisons.

PMID- 11599563
TI  - Arabidopsis thaliana Hsp100 proteins: kith and kin.
AB  - Arabidopsis thaliana, the first plant for which the entire genome sequence is
      available, was also among the first plant species from which Hsp100 proteins were
      characterized. The Athsp101 complementary DNA (cDNA) corresponds to the gene
      identification At1g74310 in the Arabidopsis genome sequence. Analysis of the
      genome revealed 7 additional proteins that are variably homologous with At1g74310
      throughout the entire amino acid sequence and significant similarities or
      identities in the signature sequences conserved among Hsp100 proteins. Although
      AtHsp101 is cytoplasmic, 5 of the 7 related proteins have predicted plastidial
      localization signals. This complete description of the AtHsp100 family sets the
      stage for future research on expression and function.

PMID- 11599564
TI  - The expanding family of Arabidopsis thaliana small heat stress proteins and a new
      family of proteins containing alpha-crystallin domains (Acd proteins).
AB  - Comprehensive analysis of the Arabidopsis genome revealed a total of 13 sHsps
      belonging to 6 classes defined on the basis of their intracellular localization
      and sequence relatedness plus 6 ORFs encoding proteins distantly related to the
      cytosolic class Cl or the plastidial class of sHsps. The complexity of the
      Arabidopsis sHsp family far exceeds that in any other organism investigated to
      date. Furthermore, we have identified a new family of ORFs encoding multidomain
      proteins that contain one or more regions with homology to the ACD (Acd
      proteins). The functions of the Acd proteins and the role of their ACDs remain to
      be investigated.

PMID- 11599565
TI  - The Hsp90 family of proteins in Arabidopsis thaliana.
AB  - The 90-kDa heat shock protein (Hsp90) is an essential molecular chaperone in
      eukaryotic cells, with key roles in the folding and activation of proteins
      involved in signal transduction and control of the cell cycle. A search for Hsp90
      sequences in the Arabidopsis thaliana genome revealed that this family includes 7
      members. The AtHsp90-1 through AtHsp90-4 proteins constitute the cytoplasmic
      subfamily, whereas the AtHsp90-5, AtHsp90-6, and AtHsp90-7 proteins are predicted
      to be within the plastidial, mitochondrial, and endoplasmic reticulum
      compartments, respectively. The deduced amino acid sequences of each of the
      cytoplasmic proteins contains the highly conserved C-terminal pentapeptide MEEVD.
      All of the AtHsp90 sequences include a conserved adenosine triphosphate-binding
      domain, whereas only the cytoplasmic and endoplasmic reticulum-resident sequences
      include an adjacent charged linker domain that is common in mammalian and yeast
      sequences. The occurrence of multiple AtHsp90 proteins in the cytoplasm and of
      family members in other subcellular compartments suggests a range of specific
      functions and target polypeptides.

PMID- 11599566
TI  - Orthologs in Arabidopsis thaliana of the Hsp70 interacting protein Hip.
AB  - The Hsp70-interacting protein Hip binds to the adenosine triphosphatase domain of
      Hsp70, stabilizing it in the adenosine 5'-diphosphate-ligated conformation and
      promoting binding of target polypeptides. In mammalian cells, Hip is a component
      of the cytoplasmic chaperone heterocomplex that regulates signal transduction via
      interaction with hormone receptors and protein kinases. Analysis of the complete
      genome sequence of the model flowering plant Arabidopsis thaliana revealed 2
      genes encoding Hip orthologs. The deduced sequence of AtHip-1 consists of 441
      amino acid residues and is 42% identical to human Hip. AtHip-1 contains the same
      functional domains characterized in mammalian Hip, including an N-terminal
      dimerization domain, an acidic domain, 3 tetratricopeptide repeats flanked by a
      highly charged region, a series of degenerate GGMP repeats, and a C-terminal
      region similar to the Sti1/Hop/p60 protein. The deduced amino acid sequence of
      AtHip-2 consists of 380 amino acid residues. AtHip-2 consists of a truncated Hip
      like domain that is 46% identical to human Hip, followed by a C-terminal domain
      related to thioredoxin. AtHip-2 is 63% identical to another Hip-thioredoxin
      protein recently identified in Vitis labrusca (grape). The truncated Hip domain
      in AtHip-2 includes the amino terminus, the acidic domain, and tetratricopeptide
      repeats with flanking charged region. Analyses of expressed sequence tag
      databases indicate that both AtHip-1 and AtHip-2 are expressed in A thaliana and
      that orthologs of Hip are also expressed widely in other plants. The similarity
      between AtHip-1 and its mammalian orthologs is consistent with a similar role in
      plant cells. The sequence of AtHip-2 suggests the possibility of additional
      unique chaperone functions.

PMID- 11599567
TI  - Heat shock protein 90 and the nuclear transport of progesterone receptor.
AB  - Steroid receptors exist as large oligomeric complexes in hypotonic cell extracts.
      In the present work, we studied the nuclear transport of the 2 major components
      of the oligomeric complex, the receptor itself and the heat shock protein 90
      (Hsp90), by using different in vitro transport systems: digitonin permeabilized
      cells and purified nuclei. We demonstrate that the stabilized oligomeric complex
      of progesterone receptor (PR) cannot be transported into the nucleus and that
      unliganded PR salt dissociated from Hsp90 is transported into the nucleus. When
      nonstabilized PR oligomer was introduced into the nuclear transport system, the
      complex dissociated and the PR but not the Hsp90 was transported into the
      nucleus. If PR exists as an oligomeric form after synthesis, as suggested by the
      experiments with reticulocyte lysate, the present results suggest that the
      complex is short-lived and is dissociated before or during nuclear transport.
      Thus, the role of Hsp90 in PR action is likely to reside in the Hsp90-assisted
      chaperoning process of PR preceding nuclear transport of the receptor.

PMID- 11599568
TI  - Stress induction of Bm1 RNA in silkworm larvae: SINEs, an unusual class of stress
      genes.
AB  - This study surveys the induction of RNA polymerase III (Pol III)-directed
      expression of short interspersed element (SINE) transcripts by various stresses
      in an animal model, silkworm larvae. Sublethal heat shock and exposure to several
      toxic compounds increase the level of Bm1 RNA, the silkworm SINE transcript,
      while also transiently increasing expression of a well-characterized stress
      induced transcript, Hsp70 messenger RNA (mRNA). In certain cases, the Bm1 RNA
      response coincides with that of Hsp70 mRNA, but more often Bm1 RNA responds later
      in recovery. Baculovirus infection and exposure to certain toxic compounds
      increase Bm1 RNA but not Hsp70 mRNA, showing that SINE induction is not
      necessarily coupled to transcription of this particular heat shock gene. SINEs
      behave as an additional class of stress-inducible genes in living animals but are
      unusual as stress genes because of their high copy number, genomic dispersion,
      and Pol III-directed transcription.

PMID- 11599569
TI  - Role of inducible heat shock protein 70 in radiation-induced cell death.
AB  - We previously demonstrated the protective effect of inducible heat shock protein
      70 (Hsp70) against gamma radiation. Herein, we extend our studies on the possible
      role of Hsp70 to ionizing radiation-induced cell cycle regulation. The growth
      rate of inducible hsp70-transfected cells was 2-3 hours slower than that of
      control cells. Flow cytometric analysis of cells at G1 phase synchronized by
      serum starvation also showed the growth delay in the Hsp70-overexpressing cells.
      In addition, reduced cyclin D1 and Cdc2 levels and increased dephosphorylated
      phosphoretinoblastoma (pRb) were observed in inducible hsp70-transfected cells,
      which were probably responsible for the reduction of cell growth. To find out if
      inducible Hsp70-mediated growth delay affected radiation-induced cell cycle
      regulation, flow cytometric and molecular analyses of cell cycle regulatory
      proteins and their kinase were performed. The radiation-induced G2/M arrest was
      found to be inhibited by Hsp70 overexpression and reduced p21Waf induction and
      its kinase activity by radiation in the Hsp70-transfected cells. In addition,
      radiation-induced cyclin A or B1 expressions together with their kinase
      activities were also inhibited by inducible Hsp70, which represented reduced
      mitotic cell death. Indeed, hsp70 transfectants showed less induction of
      radiation-induced apoptosis. When treated with nocodazole, radiation-induced
      mitotic arrest was inhibited by inducible Hsp70. These results strongly suggested
      that inducible Hsp70 modified growth delay (increased G1 phase) and reduced G2/M
      phase arrest, subsequently resulting in inhibition of radiation-induced cell
      death.

PMID- 11599570
TI  - Characterization and regulation of the major histocompatibility complex-encoded
      proteins Hsp70-Hom and Hsp70-1/2.
AB  - Vertebrate cells contain at least 12 different genes for Hsp70 proteins, 3 of
      which are encoded in the major histocompatibility complex (MHC) class III region.
      In the human MHC, these are named Hsp70-1, -2, and -Hom. To characterize these
      proteins, we have determined their substrate binding specificity, their cellular
      and tissue distribution, and the regulation of their expression. We show for the
      first time (1) peptide binding specificity of Hsp70-Hom; (2) endogenous
      expression of Hsp70-Hom in human cell lines; (3) cytoplasmic location of Hsp70
      Hom protein under basal conditions and concentration in the nucleus after heat
      shock; (4) unique RNA expression profiles in human tissues for each of the MHC
      encoded Hsp70s, significantly different from that for the constitutive Hsc70; (5)
      a relative increase in levels of Hsp70-Hom protein, compared with other Hsp70s,
      in response to interferon gamma; and (6) a specific increase on
      lipopolysaccharide (LPS) treatment of in vivo messenger RNA levels for the MHC
      encoded Hsp70s and the DnaJ homologue, hdj2, relative to other chaperones. The
      unique tissue distributions and specific up-regulation by LPS of the MHC-encoded
      Hsp70s suggest some specialization of functions for these members of the Hsp70
      family, possibly in the inflammatory response.

PMID- 11599571
TI  - Geldanamycin: the prototype of a class of antitumor drugs targeting the heat
      shock protein 90 family of molecular chaperones.

PMID- 11599572
TI  - Presence of antibody against the inducible Hsp71 in patients with acute heat
      induced illness.
AB  - Antibodies against heat shock or stress proteins (Hsps) have been reported in a
      number of diseases in which they may be involved in the pathogenesis of the
      disease or may be of use for prognosis. Heat-induced diseases, such as heat
      cramps, heat exhaustion, or heat stroke, are frequent in hot working or living
      environments. There are still few investigations on the presence and possible
      significance of autoantibodies against Hsps in heat-induced illnesses. Using an
      immunoblotting technique with recombinant human Hsps, we analyzed the presence
      and titers of antibodies against Hsp60, Hsp71, and Hsp90alpha, and Hsp90beta in a
      group of 42 young male patients who presented with acute heat-induced illness
      during training. We also examined the presence of antibody against Hsp71 in a
      second group of 57 patients with acute heat-induced illness and measured the
      changes in titers of anti-Hsp71 antibodies in 9 patients hospitalized by
      emergency physicians. In the first group of young persons exercising in a hot
      environment, the occurrence of antibodies against Hsp71 and Hsp90alpha was
      significantly higher among individuals with symptoms of heat-induced illness (P <
      0.05) than in the matched group of nonaffected exercising individuals. Moreover
      titers of antibody against Hsp71 were higher in individuals of the severe and
      mild heat-induced illness groups, the highest titer being found in the most
      severe cases. The results from the second group of 57 heat-affected patients
      exposed to extreme heat were similar. Again, patients with the more severe heat
      induced symptoms showed a significantly higher incidence of antibodies to Hsp71
      than controls and the titer of anti-Hsp71 was higher in the severely affected
      group. Finally, in a study of 9 patients, it was observed that the titer of anti
      Hsp71 decreased during recovery from severe heat symptoms. These results suggest
      that measurement of antibodies to Hsps may be useful in assessing how individuals
      are responding to abnormal stress within their living and working environment and
      may be used as one biomarker to evaluate their susceptibility to heat-induced
      diseases.

PMID- 11599573
TI  - The inducible Hsp70 as a marker of tumor immunogenicity.
AB  - Growing evidence indicates that the stress response in general and heat shock
      proteins (Hsps) in particular have a profound impact on tumor immunogenicity. In
      this study, we show that tumor cells subjected to a nonlethal heat shock stress
      are unable to form tumors in syngenic mice, whereas they do so in athymic nude
      mice. Moreover, heat-shocked MethA immunity is tumor specific. Enhancement of T
      cell-mediated immunogenicity correlates with the expression of the inducible
      Hsp70 but not the constitutive Hsc70. These observations have a bearing on the
      proposed functional role of Hsp-peptide association in antigen processing and
      presentation by major histocompatibility complex I molecules under normal and
      stressful conditions.

PMID- 11599574
TI  - Influence of trehalose on the molecular chaperone activity of p26, a small heat
      shock/alpha-crystallin protein.
AB  - Encysted embryos of the primitive crustacean Artemia franciscana are among the
      most resistant of all multicellular eukaryotes to environmental stress, in part
      due to massive amounts of a small heat shock/alpha-crystallin protein (p26) that
      acts as a molecular chaperone. These embryos also contain very large amounts of
      the disaccharide trehalose, well known for its ability to protect macromolecules
      and membranes against damage due to water removal and temperature extremes.
      Therefore, we looked for potential interactions between trehalose and p26 in the
      protection of a model substrate, citrate synthase (CS), against heat denaturation
      and aggregation and in the restoration of activity after heating in vitro. Both
      trehalose and p26 decreased the aggregation and irreversible inactivation of CS
      at 43 degrees C. At approximate physiological concentrations (0.4 M), trehalose
      did not interfere with the ability of p26 to assist in the reactivation of CS
      after heating, but higher concentrations (0.8 M) were inhibitory. We also showed
      that CS and p26 interact physically during heating and that trehalose interferes
      with complex formation and disrupts CS-p26 complexes that form at high
      temperatures. We suggest from these results that trehalose may act as a "release
      factor," freeing folding intermediates of CS that p26 can chaperone to the native
      state. Trehalose and p26 can act synergistically in vitro, during and after
      thermal stress, suggesting that these interactions also occur in vivo.

PMID- 11599575
TI  - The nuclear matrix is a thermolabile cellular structure.
AB  - Heat shock sensitizes cells to ionizing radiation, cells heated in S phase have
      increased chromosomal aberrations, and both Hsp27 and Hsp70 translocate to the
      nucleus following heat shock, suggesting that the nucleus is a site of thermal
      damage. We show that the nuclear matrix is the most thermolabile nuclear
      component. The thermal denaturation profile of the nuclear matrix of Chinese
      hamster lung V79 cells, determined by differential scanning calorimetry (DSC),
      has at least 2 transitions at Tm = 48 degrees C and 55 degrees C with an onset
      temperature of approximately 40 degrees C. The heat absorbed during these
      transitions is 1.5 cal/g protein, which is in the range of enthalpies for protein
      denaturation. There is a sharp increase in 1-anilinonapthalene-8-sulfonic acid
      (ANS) fluorescence with Tm = 48 degrees C, indicating increased exposure of
      hydrophobic residues at this transition. The Tm = 48 degrees C transition has a
      similar Tm to those predicted for the critical targets for heat-induced
      clonogenic killing (Tm = 46 degrees C) and thermal radiosensitization (Tm = 47
      degrees C), suggesting that denaturation of nuclear matrix proteins with Tm = 48
      degrees C contribute to these forms of nuclear damage. Following heating at 43
      degrees C for 2 hours, Hsc70 binds to isolated nuclear matrices and isolated
      nuclei, probably because of the increased exposure of hydrophobic domains. In
      addition, approximately 25% of exogenous citrate synthase also binds, indicating
      a general increase in aggregation of proteins onto the nuclear matrix. We propose
      that this is the mechanism for increased association of nuclear proteins with the
      nuclear matrix observed in nuclei Isolated from heat-shocked cells and is a form
      of indirect thermal damage.

PMID- 11599576
TI  - Activation of human monocyte cell line U937 via cell surface calreticulin.
AB  - U937 cells were found to be activated by an antibacterial peptide, KLKLLLLLKLK
      NH2 (L5), to generate superoxide anion (O2-)-like peripheral neutrophils.
      However, the state of cell surface calreticulin, a possible receptor for L5, was
      suggested to differ between neutrophils and U937 cells. Unlike the former, the
      latter ones were activated by anti-C-domain peptide antibody of calreticulin even
      in the absence of L5 and generated O2- in a GTP-binding protein (G-protein)
      dependent manner.

PMID- 11599577
TI  - Evaluation for Hsp70 as a biomarker of effect of pollutants on the earthworm
      Lumbricus terrestris.
AB  - Induction of heat shock proteins (Hsps) is often associated with a cellular
      response to a harmful stress or to adverse life conditions. The main aims of the
      present study were (1) to assess if stress-induced Hsp70 could be used to monitor
      exposure of the earthworm species Lumbricus terrestris to various soil
      pollutants, (2) to assess the specificity of pollutants in their tissue targeting
      and in Hsp70 induction, and (3) to evaluate if dose-response relationships could
      be established and if the stress-response observed was specific. The
      midgut/intestinal tissues of L. terrestris are shown to express an inducible
      member of the Hsp70 family after heat shock treatment in vitro and exposures to
      different soil toxicants in vivo (re: artificial soil). Short-term (24-72 hours)
      and long-term (14-16 days) exposures to the chemical standards chloroacetamide
      and pentachlorophenol and to heavy metals (Pb++, Cd++, Cu++, and Hg++) also
      affected the earthworms, and Hsp70 was induced in their midgut/intestinal
      tissues. After a 3-day exposure to heavy metals, the level of Hsp70 induction in
      the midgut/intestinal tissues appears to correlate well with the reported in vivo
      and in vitro toxicity data. Comparatively, in proximal and midbody wall muscle
      tissues of animals exposed to the heavy metals, a decrease in expression of Hsp70
      was sometimes detected. Thus Hsp analysis by Western blot in L. terrestris
      tissues and particularly in the midgut/intestine proved to be a suitable and
      sensitive assay for adverse effects in earthworms and showed a good level of
      reproducibility despite some individual variations. The use of
      pristine/nonexposed animals transposed into contaminated environments as in the
      present study should therefore be of high ecological relevance. Induction of
      Hsp70 in earthworms should represent not only a good wide-spectrum biomarker of
      exposure but also a biomarker of effect since known toxicants altered gene
      expression in tissues of these animals, as contrasted with a simple accumulation
      of Hsp. Hence, the detection of Hsp70 in earthworms can constitute an early
      warning marker for the presence of potentially deleterious agents in soils, with
      L. terrestris in particular and earthworms in general acting as potential
      sentinel animal species.

PMID- 11599578
TI  - Effects of heat shock, stannous chloride, and gallium nitrate on the rat
      inflammatory response.
AB  - Heat and a variety of other stressors cause mammalian cells and tissues to
      acquire cytoprotection. This transient state of altered cellular physiology is
      nonproliferative and antiapoptotic. In this study, male Wistar rats were stress
      conditioned with either stannous chloride or gallium nitrate, which have
      immunosuppressive effects in vivo and in vitro, or heat shock, the most
      intensively studied inducer of cytoprotection. The early stages of inflammation
      in response to topical suffusion of mesentery tissue with formyl-methionyl-leucyl
      phenylalanine (FMLP) were monitored using intravital microscopy. Microvascular
      hemodynamics (venular diameter, red blood cell velocity [Vrbc], white blood cell
      [WBC] flux, and leukocyte-endothelial adhesion [LEA]) were used as indicators of
      inflammation, and tissue levels of inducible Hsp70, determined using immunoblot
      assays, provided a marker of cytoprotection. None of the experimental treatments
      blocked decreases in WBC flux during FMLP suffusion, an indicator of increased
      low-affinity interactions between leukocytes and vascular endothelium known as
      rolling adhesion. During FMLP suffusion LEA, an indicator of firm attachment
      between leukocytes and vascular endothelial cells increased in placebo and
      gallium nitrate-treated animals but not in heat- and stannous chloride-treated
      animals, an anti-inflammatory effect. Hsp70 was not detected in aortic tissue
      from placebo and gallium nitrate-treated animals, indicating that Hsp70-dependent
      cytoprotection was not present. In contrast, Hsp70 was detected in aortic tissues
      from heat- and stannous chloride-treated animals, indicating that these tissues
      were in a cytoprotected state that was also an anti-inflammatory state.

PMID- 11599579
TI  - Role of priming stresses and Hsp70 in protection from ischemia-reperfusion injury
      in cardiac and skeletal muscle.
AB  - Ischemia-reperfusion injury limits the survival of muscle involved in tissue
      trauma or transfers during microsurgical reconstruction. Priming stresses such as
      ischemic preconditioning or mild hyperthermia have frequently been associated
      with improved survival of ischemic-reperfused cardiac muscle, such protection
      coinciding with induction of the stress-related heat shock protein 70 (Hsp70).
      Little is known about the response of skeletal muscle to priming stresses. This
      review summarizes the current knowledge on the use of priming stresses as
      protective strategies against the consequences of ischemia-reperfusion in cardiac
      and skeletal muscle and the potential role of Hsp70.

PMID- 11599581
TI  - Impact of volume-dependent alveolar diffusing capacity on exhaled nitric oxide
      concentration.
AB  - Exhaled endogenous nitric oxide (NO) holds promise as a potential biomarker of
      pulmonary inflammation. Previous experimental and theoretical work has concluded
      that the alveolar concentration approaches a constant steady state value at end
      exhalation due to both a constant maximum flux or release of NO (J(max,alv)) and
      a constant diffusing capacity (D(NO,alv)) in the alveolar region. We have
      recently demonstrated that D(NO,alv) is not constant, but increases with alveolar
      volume (VA) given by the following average relationship: D(NO,alv) =48*VA(2/3)
      ml/min/mmHg (where VA is expressed in liters, STPD). We investigated the
      potential impact of a variable D(NO,alv) on exhaled concentration by
      incorporating the volume dependence into the currently accepted two-compartment
      model for NO exchange dynamics. Our results suggest that the mechanism underlying
      the plateau in exhaled concentration is a constant ratio J(max,alv)/D(NO,alv)
      This constant ratio requires a volume dependence of J(max,alv) similar to
      D(NO,alv), and is likely due to a decreasing alveolar surface area during
      exhalation.

PMID- 11599580
TI  - Metallothionein gene expression in peripheral lymphocytes from cadmium-exposed
      workers.
AB  - Metallothionein (MT) plays an important role in the detoxification of cadmium. To
      investigate the usefulness of MT gene expression in peripheral blood lymphocytes
      (PBLs) as a biomarker of cadmium exposure and susceptibility, reverse
      transcriptase-polymerase chain reaction was used to measure the MT gene
      expression in PBLs from cadmium-exposed workers. Both basal and induced MT
      expressions were found to increase with increased blood cadmium (BCd) and urinary
      cadmium (UCd) levels. Both basal and induced MT expression levels were
      significantly correlated with the logarithm of BCd and the logarithm of UCd
      levels. The dose-response relationship between internal dose of cadmium and MT
      expression suggested the validity of MT expression in PBLs as a biomarker of
      cadmium exposure. In vitro induced MT expression level in PBLs was found to be
      inversely related to the level of renal dysfunction indicator, urinary N-acetyl
      beta-D-glucosaminidase (UNAG). The latter finding indicates that MT expression in
      PBLs may be a useful biomarker of susceptibility to renal toxicity of cadmium.

PMID- 11599582
TI  - Modulation of ATP/ADP concentration at the endothelial surface by shear stress:
      effect of flow-induced ATP release.
AB  - The adenine nucleotides ATP and ADP induce the production of vasoactive compounds
      in vascular endothelial cells (ECs). Therefore, knowledge of how flow affects the
      concentration of ATP and ADP at the EC surface may be important for understanding
      shear stress-mediated vasoregulation. The concentration of ATP and ADP is
      determined by convective and diffusive transport as well as by hydrolysis of
      these nucleotides by ectonucleotidases at the EC surface. Previous mathematical
      modeling has demonstrated that for steady flow in a parallel plate flow chamber,
      the combined ATP+ADP concentration does not change considerably over a wide range
      of shear stress. This finding has been used to argue that the effect of flow on
      adenine nucleotide transport could not account for the dependence of endothelial
      responses to ATP on the magnitude of applied shear stress. The present study
      extends the previous modeling to include pulsatile flow as well as flow-induced
      endothelial ATP release. Our results demonstrate that flow-induced ATP release
      has a pronounced effect on nucleotide concentration under both steady and
      pulsatile flow conditions. While the combined ATP+ADP concentration at the EC
      surface in the absence of flow-induced ATP release changes by only approximately
      10% over the wall shear stress range 0.1-10 dyne cm(-2), inclusion of this
      release leads to a concentration change of approximately 34%-106% over the same
      shear stress range, depending on how ATP release is modeled. These results
      suggest that the dependence of various endothelial responses to shear stress on
      the magnitude of the applied shear stress may be partially attributable to flow
      induced changes in cell-surface adenine nucleotide concentration.

PMID- 11599583
TI  - Biosynthetic activity in heart valve leaflets in response to in vitro flow
      environments.
AB  - The development of bioreactors for tissue engineered heart valves would be aided
      by a thorough understanding of how mechanical forces impact cells within valve
      leaflets. The hypothesis of the present study is that flow may influence the
      biosynthetic activity of aortic valve leaflet cells. Porcine leaflets were
      exposed to one of several conditions for 48 h, including steady or pulsatile flow
      in a tubular flow system at 10 or 20 l/min, and steady shear stress in a parallel
      plate flow system at 1, 6, or 22 dyne/cm2. Protein, glycosaminoglycan, and DNA
      synthesis increased during static incubation but remained at basal levels after
      exposure to flow. The modulation of synthetic activity was attributed to the
      presence of a shear stress on the leaflet surface, which may be transmitted to
      cells within the leaflet matrix through tensile forces. The alpha-smooth muscle
      (alpha-SM) actin distribution observed in fresh leaflets was proportionately
      decreased after exposure to antibiotics and not recovered by either static
      incubation or exposure to flow. These results indicate that exposure to flow
      maintains leaflet synthetic activity near normal levels, but that the inclusion
      of another force, such as bending or backpressure, may be necessary to preserve
      alpha-SM actin immunoreactive cells.

PMID- 11599584
TI  - Comparison and clinical application of frequency domain methods in analysis of
      neonatal heart rate time series.
AB  - The frequency content of the heart rate (HR) series contains information
      regarding the state of the autonomic nervous system. Of particular importance is
      respiratory sinus arrhythmia (RSA), the high-frequency fluctuation in HR
      attributable to respiration. The unevenly sampled nature of heart rate data,
      however, presents a problem for the discrete Fourier transform. Interpolation of
      the HR series allows even sampling, but filters high-frequency content. The Lomb
      periodogram (LP) is a regression-based method that addresses these issues. To
      evaluate the efficacy of the LP and Fourier techniques in detecting RSA, we
      compared the spectrum of intervals, the spectrum of HR samples, and the LP of
      simulated and clinical neonatal time series. We found the LP was superior to the
      spectrum of intervals and the spectrum of HR samples in analysis near the
      critical frequency of one half the average sampling rate. Applying the LP to
      clinical data, we found (1) evidence of stochastic resonance, an enhancement of
      periodicity with the addition of small amounts of noise, and (2) reduced power at
      all frequencies prior to clinical diagnosis of neonatal sepsis.

PMID- 11599585
TI  - Computer aided speckle interferometry: a technique for measuring deformation of
      the surface of the heart.
AB  - An investigation of the inhomogeneous and anisotropic properties of myocardium
      necessitates a whole field measurement technique with high spatial resolution.
      Computer aided speckle interferometry (CASI) may be applied to measuring
      deformation on the epicardial surface of the heart. Silicone carbide particles
      (approximately 40 microm in diameter) were sprinkled randomly onto the epicardial
      surface of isolated rabbit hearts. When illuminated with white light, speckles
      may be observed with a charge coupled device (CCD) camera. A balloon was placed
      in the left ventricle to control the intracavitary load on the arrested heart. To
      compare CASI to the "gold" standard technique of sonomicrometry, two ultrasonic
      transducers were implanted into the wall of the myocardium. Three hearts were
      exposed to various loading conditions, and at each condition speckle images were
      recorded. CASI was used to determine the distribution of displacement vectors
      (both direction and magnitude) in the region imaged by the CCD camera. Strain
      along the axis of the implanted transducers was determined with CASI and compared
      to that obtained with sonomicrometry. Strain determined from CASI and
      sonomicrometry produced equivalent results. Unlike sonomicrometry, whereby the
      displacement between two points with a relatively large gauge length is obtained,
      CASI is able to determine displacement vectors for hundreds of "points" within
      the same region. In conclusion, CASI produced equivalent results to those
      obtained from sonomicrometry (although not with the same temporal resolution),
      but it is a whole field deformation mapping technique that has a spatial
      resolution three orders of magnitude higher than that of sonomicrometry.

PMID- 11599586
TI  - Ultrasonic wave propagation in trabecular bone predicted by the stratified model.
AB  - The objective of this study was to investigate ultrasound propagation in
      trabecular bone by considering the wave reflection and transmission in a
      multilayered medium. The use of ultrasound to identify those at risk of
      osteoporosis is a promising diagnostic method providing a measure of bone mineral
      density (BMD). A stratified model was proposed to study the effect of
      transmission and reflection of ultrasound wave within the trabecular architecture
      on the relationship between ultrasound and BMD. The results demonstrated that
      ultrasound velocity in trabecular bone was highly correlated with the bone
      apparent density (r=0.97). Moreover, a consistent pattern of the frequency
      dependence of ultrasound attenuation coefficient has been observed between
      simulation using this model and experimental measurement of trabecular bone. The
      normalized broadband ultrasound attenuation (nBUA) derived from the simulation
      results revealed that nBUA was nonlinear with respect to trabecular porosity and
      BMD. The curve of the relationship between nBUA and BMD was parabolic in shape,
      and the peak magnitude of nBUA was observed at approximately 60% of bone
      porosity. These results agreed with the published experimental data and
      demonstrated that according to the stratified model, reflection and transmission
      were important factors in the ultrasonic propagation through the trabecular bone.

PMID- 11599587
TI  - Stimulus induced pH changes in cochlear implants: an in vitro and in vivo study.
AB  - Large pH changes have been shown to be potentially harmful to tissue. The present
      study was designed to examine stimulus induced changes in pH for a variety of
      stimulus parameters both in vitro and in vivo, in order to ensure that
      stimulation strategies for neural prostheses result in minimal pH change.
      Stimulation using charge balanced biphasic pulses at intensities both within and
      well above maximum clinical levels for cochlear implants (0.025-0.68 microC per
      phase), were delivered to platinum electrodes in vitro [saline, phosphate
      buffered saline (PBS), or saline with human serum albumin (HSA)], and in vivo
      (scala tympani). Stimulus rates were typically varied from 62.5 to 1000 pulses
      per second (pps), although rates of up to 14,500 pps were used in some
      experiments. The pH level was recorded using a pH indicator (Phenol red) or pH
      microelectrodes. While electrical stimulation at intensities and rates used
      clinically showed no evidence of a pH shift, intensities significantly above
      these levels induced pH changes both in vitro and in vivo. The extent of pH
      change was related to stimulus rate and intensity. In addition, pH change was
      closely associated with the residual direct current (dc) level. As expected,
      stimulation with capacitive coupling induced little dc and a minimal pH shift.
      Moreover, no pH shift was observed using alternating leading phase pulse trains
      at intensities up to 0.68 microC per phase and 1000 pps. Saline with HSA or
      buffered solutions dramatically reduced the extent of pH shift observed following
      stimulation in unbuffered inorganic saline. Reduced pH shift was also observed
      following in vivo stimulation. These findings provide an insight into mechanisms
      of safe change injection in neural prostheses.

PMID- 11599588
TI  - Corrosion properties of nanocrystalline Co-Cr coatings.
AB  - Nanocrystalline and conventional Co-Cr (ASTM F75) coatings were prepared by
      plasma spraying for possible orthopedic implant applications. Scanning electron
      microscopy and transmission electron microscopy were used to study the
      macrostructure and microstructure of the resultant sprayed coatings. The
      corrosion resistance was characterized by an in vitro potentiodynamic anodic
      polarization technique in a pseudophysiological solution. The nanocrystalline
      coating has higher porosity, lower corrosion current density, and less localized
      damage than that of the conventional one, demonstrating better application
      potential for orthopedic implants. A change in the atomic compositional
      difference between the grain interior and the grain boundary, the presence of
      residual strain in the grain interiors, and a change in the repassivation
      kinetics are discussed as possible explanations for the enhanced corrosion
      behavior observed.

PMID- 11599589
TI  - Mixing mechanisms and net solute transport in bone.

PMID- 11599591
TI  - A validated liquid chromatography-atmospheric pressure chemical ionization-tandem
      mass spectrometry method for quantitation of cocaine and benzoylecgonine in human
      plasma.
AB  - In order to support studies on various medication protocols for the treatment of
      cocaine abuse, an accurate, precise, and sensitive (2.5 to 750 ng/mL) liquid
      chromatography-tandem mass spectrometry assay was developed to determine cocaine
      and benzoylecgonine in human plasma. Cocaine-d3 and benzoylecgonine-d3 were added
      as internal standards and samples were subjected to solid-phase extraction.
      Cocaine recovery was 94.4% and benzoylecgonine was 80.3% at 2.5 ng/mL. The
      selected reaction monitoring of parent ions at m/z 304 and 290 resulted in strong
      fragments at m/z 182 and 168 for cocaine and benzoylecgonine, respectively. The
      method was fully validated. The mean measured concentration at the 2.5 ng/mL, the
      lower limit of quantitation, was within 10.8% of the target and the precision
      determined at the low (5 ng/mL), medium (50 ng/mL), and high (650 ng/mL) quality
      controls ranged from 0.9 to 6.2 %CV. Cocaine and benzoylecgonine concentrations
      in plasma treated with 1% NaF showed changes of less than 10% when maintained at
      room temperature for up to 7 h and no significant changes when subjected to three
      freeze-thaw cycles. The concentrations of cocaine and benzoylecgonine remained
      stable in plasma samples stored at -20 degrees C for up to 11 months. Methanolic
      stock solutions of both analytes are stable, staying within 2% of the freshly
      prepared stock solutions, when stored at -20 degrees C for up to 235 days. Both
      extracted analytes reconstituted in methanolic solutions are stable for up to
      seven days whether stored at -20 degrees C or at room temperature on the
      autosampler. The method is rugged, rapid, and robust and has been applied to the
      batch analysis of more than 700 samples during pharmacokinetic profiling to
      assess potential interactions between intravenous (i.v.) cocaine challenge and
      treament medications. Results from three of these subjects receiving 40 mg (i.v.)
      cocaine demonstrate the utility of the method.

PMID- 11599590
TI  - Effect of four laboratory decontamination procedures on the quantitative
      determination of cocaine and metabolites in hair by HPLC-MS.
AB  - The testing for drugs of abuse in hair is increasingly used to detect illicit
      substances. Laboratories have implemented various decontamination, or washing,
      procedures in order to eliminate concerns regarding potential contamination of
      the hair with drug from the environment. However, the effect of these
      decontamination procedures on drug incorporated into the hair shaft via systemic
      exposure is unknown. This study evaluated the effect of four simple laboratory
      wash procedures on the quantitative measurement of cocaine and its metabolites in
      hair from rats administered cocaine by intraperitoneal injection. Washes included
      (1) methanol only; (2) 0.1 M phosphate buffer, pH 6.0; (3) 0.1 M phosphate
      buffer, pH 8.0; and (4) isopropanol and phosphate buffer, pH 5.5. Cocaine and its
      major metabolites, benzoylecgonine, norcocaine, ecgonine methyl ester, and
      cocaethylene, were analyzed using high-performance liquid chromatography coupled
      to atmospheric pressure electrospray ionization mass spectrometry. All four
      washes resulted in significant differences from unwashed hair controls (p < or =
      0.05) for some or all of the detectable analytes. Because different wash
      procedures lead to significant differences in the measured concentrations of
      analytes in hair known to contain drug, quantitative data must be interpreted
      cautiously based on the wash procedures employed.

PMID- 11599592
TI  - Urinary excretion profiles for total morphine, free morphine, and 6
      acetylmorphine following smoked and intravenous heroin.
AB  - Heroin is one of the major target drugs in workplace drug-testing programs
      because of its history of abuse, liability, and continued negative social impact.
      This study was a comprehensive examination of pharmacokinetics, pharmacodynamics,
      detection times, opiate immunoassay performance, and urine excretion profiles
      following single doses of heroin administered to human subjects via smoking and
      intravenous routes. Studies of the first four components of this investigation
      were previously published. This article describes the urine excretion profiles.
      Total morphine (Tmor), free morphine (Fmor), and 6-acetylmorphine (6-AM) were
      measured by gas chromatography-mass spectrometry (GC-MS) in 920 urine samples
      collected from 11 male human subjects following single doses of heroin. Eight
      received intravenous doses of 3, 6, and 12 mg heroin HCI and four smoked 3.5-,
      5.2-, 7-, 10.5-, or 13.9-mg doses of heroin (base). In addition, 183 urine-based
      blind quality-control samples were added to the study set to assess assay
      performance. Creatinine was also measured in each sample by a colorimetric
      technique. The parameters studied were not significantly dependent on route of
      administration. Excretion half-life mean +/- SD for Tmor was 3.11 +/- 0.30 h.
      Range (median) of peak urine concentrations, time to peak, time to last positive
      sample for low cutoff (300 ng/mL) and high cutoff (2000 ng/mL) for Tmor following
      lower doses (< or = 7 mg) were, respectively, 1392-9250 (3620) ng/mL, 1.2-6.2
      (2.3) h, 7.4-31.9 (7.4) h, and 0-10.1 (4.3) h. Following higher doses (> 10 mg)
      they were 2065-29,030 (16,470) ng/mL, 2.3-9.3 (4.5) h, 10.7-53.5 (34.4) h, 2.3
      22.3 (8.3) h. Fmor peaked in the same sample as Tmor. Range (median) of peak Fmor
      concentrations and time to last positive using a cutoff of 100 ng/mL for low and
      high doses were, respectively, 117-1160 (415) ng/mL, 1.2-10.1 (4.5) h and 150
      2580 (1400) ng/mL, 2.3-29.1 (9.3) h. The range (median) of peak urine
      concentrations for 6-AM was 6.1-568 (124) ng/mL. In general, the first urine void
      had the peak 6-AM concentration and was the only specimen positive at a 10-ng/mL
      cutoff. As previously reported urine concentrations varied greatly between
      subjects and within subjects with time after dosing but were much more
      predictable when values were reported as amount of drug per unit of creatinine.
      The range (median) values for percent of heroin excreted into urine as Tmor was
      12.8-88.5% (51.0).

PMID- 11599593
TI  - Detection of opiate use in a methadone maintenance treatment population with the
      CEDIA 6-acetylmorphine and CEDIA DAU opiate assays.
AB  - Heroin, with a plasma half-life of approximately 5 min, is rapidly metabolized to
      6-acetylmorphine (6-AM). 6-AM, a specific marker for heroin use, which also has a
      short half-life of only 0.6 h, is detected in urine for only a few hours after
      heroin exposure. Ingestion of poppy seeds and/or licit opiate analgesics can
      produce positive urine opiate tests. This has complicated the interpretation of
      positive opiate results and contributed to the decision to raise opiate cutoff
      concentrations and to require 6-AM confirmation in federally mandated workplace
      drug-testing programs. Microgenics Corp. has developed the CEDIA 6-AM assay, a
      homogeneous enzyme immunoassay for semiquantitative determination of 6-AM in
      human urine, in addition to its CEDIA DAU opiate assay. Urine specimens were
      collected 3 times per week from 27 participants enrolled in a clinical research
      trial evaluating a contingency management treatment program for heroin and
      cocaine abuse. Of the 1377 urine specimens screened, 261 (18.9%) were positive
      for opiates at > or = 300 ng/mL, 153 (11.1%) were positive for opiates at > or =
      2000 ng/mL, and 55 (4.0%) were positive for 6-AM at > or = 10 ng/mL. For opiate
      positive screens > or = 300 and > or = 2000 ng/mL, 91.3% and 80.8% confirmed
      positive for morphine or codeine at the respective gas chromatography-mass
      spectrometry (GC-MS) cutoffs. All specimens screening positive for 6-AM also
      confirmed positive by GC-MS at > or = 10 ng/mL. Increasing the opiate screening
      and confirmation cutoffs for the federal workplace drug-testing program resulted
      in 8% fewer opiate-positive tests; however, recent heroin use was not affected by
      this change.

PMID- 11599594
TI  - Gas chromatography-mass spectrometry confirmation of Cozart RapiScan saliva
      methadone and opiates tests.
AB  - The object of this study was to determine the sensitivity and specificity of the
      Cozart RapiScan onsite saliva test for methadone and opiates versus laboratory
      based enzyme immunoassay (EIA) and gas chromatography-mass spectrometry (GC-MS)
      confirmation. Fifty saliva specimens were obtained from 28 volunteers among
      persons entering a substance abuse clinic. Specimens were tested onsite using the
      Cozart RapiScan Saliva test and Cozart RapiScan Reader. Specimens were retested
      by Cozart Microplate EIA assays on receipt at the laboratory and then frozen for
      later confirmation by GC-MS. For GC-MS, deuterated internal standards were added
      to specimen aliquots which were extracted using solid-phase columns at pH 6 and
      eluted with dichloromethane/isopropanol/ammonia (80:19:2). The dry residues were
      derivatized with PFOH and PFPA and dried, and the reconstituted extract was
      injected and quantitated by GC-MS. The Cozart RapiScan Methadone Saliva Assay was
      found to have a sensitivity and specificity of 100% +/- 12% versus GC-MS (2-ng/mL
      cutoff) and a sensitivity of 100% +/- 11% and a specificity of 95% +/- 2.4%
      versus the Microplate EIA for methadone (30-ng/mL cutoff). The Cozart RapiScan
      Saliva Opiate test had a sensitivity of 100% +/- 12% and a specificity of 92% +/-
      3.2% versus GC-MS (2-ng/mL cutoff) and a sensitivity of 96% +/- 2.2% and
      specificity of 95% +/- 2.4% versus the Microplate EIA for opiates (30-ng/mL
      cutoff).

PMID- 11599595
TI  - Cathinone (Khat) and methcathinone (CAT) in urine specimens: a gas
      chromatographic-mass spectrometric detection procedure.
AB  - A gas chromatographic-mass spectrometric procedure for detection of cathinone
      (Khat) and methcathinone (CAT) in urine was developed. The compounds were
      detected as 4-carboethoxyhexafluorobutyryl derivatives. Three ions for the drugs
      and two ions for the internal standards were monitored. The drugs were identified
      by comparing retention times and ion ratios with that of reference compounds. The
      concentrations were measured by using amphetamine-d6 as internal standard for
      cathinone and methamphetamine-d9 as internal standard for methcathinone, and were
      linear over the range of 25-5000 ng/mL for cathinone and 12.5-5000 ng/mL for
      methcathinone. The overall recoveries of cathinone and methcathinone were 86 and
      78%, respectively. Intrarun and inter-run variations were < 20%. To verify that
      the drugs are not metabolites of over-the-counter medications, cathinone and
      methcathinone were tested in urine specimens collected from individuals who
      ingested phenylpropanolamine and pseudoephedrine. None of the specimens showed
      the keto-amines as the metabolic products. When the procedure was applied to test
      66 amphetamine-immunoassay-positive specimens containing no amphetamine or
      methamphetamine, two specimens were found positive for cathinone (118 and 3266
      ng/mL) and six specimens were found positive for methcathinone (13-91 ng/mL).

PMID- 11599596
TI  - Simultaneous determination of delta9-tetrahydrocannabinol and 11-nor-9-carboxy
      delta9-tetrahydrocannabinol in human plasma by solid-phase extraction and gas
      chromatography-negative ion chemical ionization-mass spectrometry.
AB  - Delta9-tetrahydrocannabinol (THC) and 11-nor-9-carboxy-delta9
      tetrahydrocannabinol (THCA) in human plasma can be simultaneously detected using
      solid-phase extraction with gas chromatography and negative ion chemical
      ionization mass spectrometry. THC-d3 and THCA-d3 are added as internal standards;
      protein is precipitated with acetonitrile and the resulting supernatants diluted
      with 0.1 M sodium acetate (pH 7.0) prior to application to the solid-phase
      extraction columns. THC and THCA were eluted separately and then pooled, dried
      under air, and derivatized with trifluoroacetic anhydride and
      hexafluoroisopropanol. The derivatized THC-d0 gives abundant molecular anions
      (m/z 410), and the derivatized THCA-d0 gives abundant fragment ions (m/z 422)
      formed by loss of (CF3)2CHOH from its molecular anion. The recoveries of THC and
      THCA were 74% and 17%, respectively. The lower and upper limits of quantitation
      were 0.5 and 100 ng/mL for THC and 2.5 ng/mL and 100 ng/mL for THCA. The within
      run accuracy and precision for THC (measured at 0.5, 1, 10 and 75 ng/mL) ranged
      from 98 to 106% (% target) and 4.1 to 9.5 (%CV), respectively. For THCA, the
      within-run accuracy and precision (measured at 2.5, 5, 10, and 75 ng/mL) ranged
      from 89 to 101% and 4.3 to 7.5%, respectively. The between-run accuracy and
      precision for THC ranged from 92 to 110% and 0.4 to 12.4%, respectively. The
      between-run accuracy and precision for THCA ranged from 97 to 103% and 6.5 to
      12.3%, respectively. In processed samples stored in reconstituted form at -20
      degrees C, THC and THCA were stable for at least three days. THC and THCA stored
      in plasma were stable following three freeze/thaw cycles. THC and THCA in whole
      blood at room temperature for 6 h, or in plasma stored at room temperature for 24
      h, did not show significant change. Storage in polypropylene containers for 7
      days at -20 degrees C and the presence of 1% sodium fluoride or the cannabinoid
      receptor antagonist, SR141716, at 1 microg/mL did not interfere with the
      quantitation of THC and THCA. In three individuals who smoked marijuana under
      controlled dosing conditions, peak THC concentrations of 151, 266, and 99 ng/mL
      were seen in the first plasma samples drawn immediately after the end of smoking,
      and corresponding peak THCA concentrations of 41, 52, and 17 ng/mL occurred at
      0.33 to 1 h after cessation of smoking.

PMID- 11599597
TI  - Temporal indication of marijuana use can be estimated from plasma and urine
      concentrations of delta9-tetrahydrocannabinol, 11-hydroxy-delta9
      tetrahydrocannabinol, and 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid.
AB  - Current technology establishes marijuana use based upon detection of the
      pharmacologically inactive cannabinoid metabolite (11-nor-delta9-carboxy
      tetrahydrocannabinol-9-carboxylic acid, THC-COOH) in urine. No accurate
      prediction of time of use is possible because THC-COOH has a half-life of 6 days.
      To determine if a temporal relationship between marijuana use and metabolite
      excretion patterns could be established, eight healthy user-volunteers (18-35
      years old) smoked marijuana cigarettes containing 0% (placebo), 1.77%, and 3.58%
      delta9-tetrahydrocannabinol (THC). Plasma and urine were collected prior to
      smoking, 5 min after smoking, and hourly thereafter for 8 h for measurement of
      cannabinoid concentrations by gas chromatography-mass spectrometry. Mathematical
      models proposed for determination of recent marijuana use were applied to data
      from this study and verified the temporal use of marijuana. One subject, who
      later admitted chronic marijuana use (urine baseline THCCOOH, 529.2 ng/mL;
      plasma, 75.5 ng/mL), excreted 8beta-dihydroxy-THC, peaking 2 h postsmoking (92.3
      ng/mL). Urinary THC, the psychoactive component of marijuana, concentrations
      peaked 2 h after smoking and declined to assay limit of detection (LOD) (1.5
      ng/mL) by 6 h. 11-Hydroxy-delta9-tetrahydrocannabinol (11-OH-THC) and THCCOOH
      were detectable for the entire 8-h testing period but continued to decrease.
      Urinary concentrations of THC greater than 1.5 ng/mL suggests marijuana use
      during the previous 8-h time period.

PMID- 11599598
TI  - Solid-phase extraction and GC-MS analysis of THC-COOH method optimized for a high
      throughput forensic drug-testing laboratory.
AB  - In order to facilitate the confirmation analysis of large numbers of urine
      samples previously screened positive for delta9-tetrahydrocannabinol (THC), an
      extraction, derivitization, and GC-MS analysis method was developed. This method
      utilized a positive pressure manifold anion-exchange polymer-based solid-phase
      extraction followed by elution directly into the automated liquid sampling (ALS)
      vials. Rapid derivitization was accomplished using pentafluoropropionic
      anhydride/pentafluoropropanol (PFPA/PFPOH). Recoveries averaged 95% with a limit
      of detection of 0.875 ng/mL with a 3-mL sample volume. Performance of 11-nor
      delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH)-d3 and THC-COOH-d9
      internal standards were evaluated. The method was linear to 900 ng/mL THC-COOH
      using THC-COOH-d9 with negligible contribution from the internal standard to very
      weak samples. Excellent agreement was seen with previous quantitations of human
      urine samples. More than 1000 human urine samples were analyzed using the method
      with 300 samples analyzed using an alternate qualifier ion (m/z 622) after some
      interference was observed with a qualifier ion (m/z 489). The 622 ion did not
      exhibit any interference even in samples with interfering peaks present in the
      489 ion. The method resulted in dramatic reductions in processing time, waste
      production, and exposure hazards to laboratory personnel.

PMID- 11599599
TI  - The determination of 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC
      COOH) in hair using negative ion gas chromatography-mass spectrometry and high
      volume injection.
AB  - The determination of 11-nor-delta9-THC-9-carboxylic acid (THC-COOH) in hair
      specimens at the sensitivity required to detect marijuana users is a difficult
      analytical problem. A sensitive and specific method has been developed for the
      quantitative assay of THC-COOH in hair. Hair specimens were washed, incubated in
      sodium hydroxide, subjected to solid-phase extraction, and analyzed using high
      volume injection coupled with negative chemical ionization (NCI) mass
      spectrometry. A common disadvantage of chemical ionization, the production of a
      single mass-to-charge ratio ion, was also addressed. By specific selection of the
      derivatizing agent, three ions were monitored, allowing the calculation of two
      ion ratios, as in electron impact mode. The method was applied to several hair
      specimens taken from known marijuana users and workplace specimens. This is the
      first publication describing the use of high-volume injection and NCI mass
      spectrometry for the determination of THC-COOH in hair.

PMID- 11599600
TI  - A comparison of Roche Kinetic Interaction of Microparticles in Solution (KIMS)
      assay for cannabinoids and GC-MS analysis for 11-nor-9-carboxy-delta9
      tetrahydrocannabinol.
AB  - In this study, we investigated the effectiveness of the Roche Kinetic Interaction
      of Microparticles in Solution (KIMS) screening assay for cannabinoid metabolites.
      Urine specimens (N = 1689) were collected during elimination of cannabinoids from
      25 subjects with a history of marijuana use. Specimens were analyzed concurrently
      for cannabinoid metabolites by a customized Department of Defense (DOD)
      cannabinoid KIMS kit (50-ng/mL cutoff) and for 11-nor-9-carboxy-delta9
      tetrahydrocannabinol (THC-COOH) by GC-MS (15-ng/mL cutoff). As compared to GC-MS
      results, the sensitivity, specificity, and efficiency of the KIMS assay were
      69.7%, 99.8%, and 88.6%, respectively. Many of the false-negative results had GC
      MS concentrations between 15 and 26 ng/mL (N = 151). The cannabinoid screening
      results for the DOD samples tested by the laboratory during the same 8-month
      period were also evaluated. The linear regression analyses of GC-MS results in
      the 15-50 ng/mL range and KIMS data resulted in regression coefficients of 0.689
      for the research specimens and 0.546 for DOD specimens. The results suggest that
      the KIMS cannabinoid screening assay is deficient in detecting positives around
      the cutoff (15-25 ng/mL THC-COOH). This limitation of the KIMS cannabinoid
      screening method compromises the identification of true positive specimens,
      therefore reducing the effectiveness of the assay. The success of the DOD program
      is dependent on sensitive and specific screening assays; the high prevalence of
      false-negative cannabinoid results compromises the program's primary objective of
      drug deterrence.

PMID- 11599601
TI  - Delta9-tetrahydrocannabivarin as a marker for the ingestion of marijuana versus
      Marinol: results of a clinical study.
AB  - Delta9-tetrahydrocannabinol (THC), the main psychologically active ingredient of
      the cannabis plant (marijuana), has been prepared synthetically and used as the
      bulk active ingredient of Marinol, which was approved by the FDA for the control
      of nausea and vomiting in cancer patients receiving chemotherapy and as an
      appetite stimulant for AIDS patients. Because the natural and the synthetic THC
      are identical in all respects, it is impossible to determine the source of the
      urinary metabolite of THC, 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid
      (THC-COOH), in a urine specimen provided in a drug-testing program. Over the last
      few years there has been a need to determine whether a marijuana positive drug
      test is the result of the ingestion of marijuana (or a related product) or
      whether it results from the sole use of Marinol. We have previously proposed the
      use of delta9-tetrahydrocannabivarin (THCV, the C3 homologue of THC) as a marker
      for the ingestion of marijuana (or a related product) because THCV is a natural
      component of most cannabis products along with THC and does not exist in Marinol.
      We have also reported that THCV is metabolized by human hepatocytes to 11-nor
      delta9-tetrahydrocannabivarin-9-carboxylic acid (THCV-COOH); therefore, the
      presence of the latter in a urine specimen would indicate that the donor must
      have used marijuana or a related product (with or without Marinol). In this
      study, we provide clinical data showing that THCV-COOH is detected in urine
      specimens collected from human subjects only after the ingestion of marijuana and
      not after the ingestion of Marinol (whether the latter is ingested orally or by
      smoking). Four subjects (male and female) participated in the study in a three
      session, within-subject, crossover design. The sessions were conducted at one
      week intervals. Each subject received, in separate sessions and in randomized
      order, an oral dose of Marinol (15 mg), a smoked dose of THC (16.88 mg) in a
      placebo marijuana cigarette, or a smoked dose of marijuana (2.11% THC and 0.12%
      THCV). Urine samples were collected and vital signs were monitored every 2 h for
      a 6-h period following drug administration. Subjects were then transported home,
      were given sample collection containers and logbooks, and were instructed to
      record at home the volume and time of every urine collection for 24 h, and once a
      day for the remainder of a week (6 days). Subjects were also instructed to freeze
      the urine samples until the next session. All urine samples were analyzed by GC
      MS for THC-COOH and THCV-COOH using solid-phase extraction and derivatization
      procedure on RapidTrace and TBDMS as the derivative. The method had a limit of
      detection of 1.0 ng/mL and 1.0 ng/mL for THCV-COOH and THC-COOH, respectively.

PMID- 11599602
TI  - Analysis of morphine and codeine in samples adulterated with Stealth.
AB  - Stealth is an adulterant used to avoid detection of drug abuse. The product does
      have an effect on the ability to detect several drugs of abuse, including the
      opiates morphine and codeine. It has previously been shown that low concentration
      (2500 ng/mL morphine) samples adulterated with Stealth tested negative by both
      Roche OnLine and Microgenics CEDIA immunoassays, but those spiked with higher
      concentrations (6000 ng/mL of codeine and morphine glucuronide) were positive.
      Initial results showed confirmation analysis was also sometimes negatively
      impacted by this adulterant. Urine samples were spiked with 6000 ng/mL of codeine
      and/or morphine glucuronide to assess the effect of Stealth. Each individual
      sample was split into separate aliquots. One aliquot of each was adulterated with
      Stealth following package directions. The samples were then tested by immunoassay
      and gas chromatography-mass spectrometry (GC-MS). The control and adulterated
      aliquots were positive by both immunoassays. Results of GC-MS analysis of the
      Stealth-adulterated aliquots following standard procedures using deuterated
      internal standards proved unsuccessful in several cases. In 4 of 12 cases (33%),
      neither the drugs nor internal standards were recovered despite repeated
      attempts. In one other sample, recovery was dramatically reduced, making accurate
      quantitation impossible, whereas the unadulterated aliquots of the same samples
      posed no problem with recovery. Addition of sodium disulfite to the aliquots
      prior to extraction allowed recovery of the drugs and internal standards from all
      samples. Analysis of the samples showed the concentration of morphine and codeine
      decreased in some by as much as 17 and 30%, respectively. In other cases, there
      was essentially no difference in the concentration seen before and after
      adulteration, with or without disulfite treatment. Unless the initial
      concentration of opiate is near the cutoff, samples containing opiates are likely
      to be immunoassay positive, it is important to consider this procedure as an
      option for samples that screen positive but the opiates and their respective
      internal standards are not recovered for GC-MS analysis.

PMID- 11599603
TI  - Application of a convenient extraction procedure to analyze gamma-hydroxybutyric
      acid in fatalities involving gamma-hydroxybutyric acid, gamma-butyrolactone, and
      1,4-butanediol.
AB  - The most common chemicals that can be ingested and lead to greater than
      endogenous levels of gamma-hydroxybutyric acid (GHB) in decedents are salts of
      GHB, gamma-butyrolactone (GBL), and 1,4-butanediol (BD). Results for three deaths
      involving the ingestion of one or another of these three chemicals, which led to
      findings of GHB in the decedents, are presented. An extraction procedure that
      facilitates the quantitation of GHB was developed. If present in the same
      specimen, both GHB and GBL can be quantitated. To determine the GBL
      concentration, the specimen is first analyzed for existing GHB, the GBL is then
      converted to GHB, and the analysis is repeated. The difference between the
      results in molarity units can yield the GBL concentration. A separate procedure
      was utilized for estimating concentrations of BD. Specimens analyzed included
      urine, blood, ocular fluid, brain, and solutions consumed by the decedents prior
      to death. The procedures were found to be convenient in as much as they are
      relatively rapid, precise, and economical.

PMID- 11599604
TI  - Urine concentrations of ketamine and norketamine following illegal consumption.
AB  - Ketamine, an anesthetic agent primarily used in veterinary medicine and
      pediatrics, continues to gain in popularity in the drug abuse scene or 'Rave
      Wave' of all-night dance clubs. The Division of Forensic Toxicology Laboratory
      (Office of the Armed Forces Medical Examiner) at the Armed Forces Institute of
      Pathology, as the primary analytical laboratory for criminal investigative
      agencies in the Department of Defense (DOD), has seen requests for ketamine
      analysis rise from 1 in 1997 to 116 in 2000. This increasing abuse has led the
      DOD Urine Drug Testing Laboratories to consider adding ketamine screening to
      their random urinalysis program. However, before ketamine testing can be
      implemented as standard policy, concentrations of ketamine and metabolites in
      urine need to be evaluated after actual drug use. There is very little
      information regarding the pharmacokinetics of ketamine, especially concentrations
      of the drug or its two major metabolites, norketamine and dehydronorketamine,
      that can be expected in urine. In fact, dehydronorketamine has been believed to
      be an analytical artifact caused by the high temperatures of gas chromatography.
      In this paper, we attempt to resolve this issue with the development of a liquid
      chromatography-mass spectrometry (LC-MS) method. The urine concentrations of
      ketamine, norketamine and dehydronorketamine (presumptive) detected in 33
      "positive" cases received in our laboratory since 1998 are reported.
      Quantitations were accomplished with LC-MS. Ketamine concentrations ranged from 6
      to 7744 ng/mL. Norketamine concentrations ranged from 7 to 7986 ng/mL and
      dehydronorketamine (presumptive) concentrations ranged from 37 to 23,239 ng/mL.

PMID- 11599605
TI  - Hydrolysis of conjugated metabolites of buprenorphine. I. The quantitative
      enzymatic hydrolysis of buprenorphine-3-beta-D-glucuronide in human urine.
AB  - Buprenorphine, which is a powerful analgesic, a substitution drug for opioids
      widely used in Europe, and a promising new drug currently undergoing clinical
      trials in the treatment of opioid dependence in the U.S., is excreted in human
      urine mainly as glucuronide conjugates. In gas chromatographic-mass spectrometric
      analysis, the urine specimens must be first hydrolyzed to release buprenorphine
      from its glucuronide conjugates. In order to evaluate the existing hydrolysis
      methods and to find the optimal hydrolysis conditions, buprenorphine-3-beta-D
      glucuronide (B3G) was synthesized. Urine fortified with synthetic B3G was
      hydrolyzed using acid, base, and beta-glucuronidases from different source
      species, including Helix pomatia, Escherichia coli, and Patella vulgata.
      Glusulase, a preparation containing both beta-glucuronidase (H. pomatia) and
      sulfatase, was also tested. Whereas both acidic and basic hydrolysis were
      ineffective, quantitative hydrolysis could be achieved by using beta
      glucuronidases under appropriate conditions. However, we found that there was a
      marked difference in the reactivity of these enzymes (E. coli > H. pomatia >> P.
      vulgata). The optimal incubation conditions for enzymatic hydrolysis of B3G were
      2 h at 37 degrees C for E coli and 4 h at 60 degrees C or 16 h at 37 degrees C
      for H. pomatia. Using 1000 Fishman units of either of these two enzymes,
      effective hydrolysis could be achieved even when the B3G concentration was as
      high as 2000 ng/mL. Glusulase was equally effective toward B3G if the fortified
      urine samples were incubated with 25 microL of this enzyme for 1 h at 60 degrees
      C.

PMID- 11599606
TI  - Incorporation of selegiline metabolites into hair after oral selegiline intake.
AB  - We have previously shown that melanin in human hair has a great impact on the
      incorporation of codeine into hair. The present study on 10 subjects was
      performed to investigate whether or not these findings could also be extrapolated
      to other therapeutic drugs. We chose selegiline because it metabolizes to two
      commonly abused central stimulants, methamphetamine and amphetamine. The results
      would therefore also be of interest when studying the intake of such drugs and
      their incorporation into human hair. Selegiline and metabolites were determined
      by gas chromatography-mass spectrometry, total melanin by spectrophotometry, and
      pyrrole-tricarboxylic acid by high-performance liquid chromatography with
      ultraviolet detection. Our results show strong positive exponential relationships
      (y = e(x)) between melanin and the metabolites, which for methamphetamine
      improved by normalizing for plasma area under the curve. We conclude that the
      major metabolites of selegiline can be detected in hair up to four weeks after a
      single oral dose and that the incorporation closely relates to the melanin
      contents.

PMID- 11599607
TI  - Development of a generic method to the solid-phase extraction of acidic compounds
      from complex matrices.
AB  - A mixed-mode solid-phase extraction procedure was developed for the isolation and
      purification of acidic compounds from complex biological matrices. Urine samples
      were spiked with several acidic drugs and diluted in ammonium acetate buffer.
      Isolute HAX columns (a mixed-mode phase consisting of both hydrophobic and ion
      exchange ligands) were conditioned with methanol and ammonium acetate prior to
      sample loading. Once the samples were loaded, the cartridges were rinsed
      sequentially with ammonium acetate and a 50:50 ratio of methanol and deionized
      water. The analytes were eluted with an 80:20 ratio of methanol and acetic acid.
      The eluates were evaporated to dryness and reconstituted to a final volume with a
      98:2:0.1 ratio of deionized water, acetonitrile, and trifluoroacetic acid.
      Samples were analyzed by high-performance liquid chromatography. The absolute
      recoveries for most of the tested acidic drugs exceeded 80% at an original
      concentration of 1 microg/mL. Hydrophobic and ion-exchange sorbents were also
      investigated separately; however, the retention of the analytes suffered during
      sample application as well as the purity of the eluted extract. Results on anion
      exchange columns show that the correct choice of counter-ion is extremely
      important to the retention of acidic analytes. The highest absolute recoveries
      were obtained when acetate was the counter-anion on the ion-exchange sorbent.

PMID- 11599608
TI  - 3H-nicotine, 3H-flunitrazepam, and 3H-cocaine incorporation into melanin: a model
      for the examination of drug-melanin interactions.
AB  - To explore drug-melanin interactions, we examined the in vitro tyrosinase
      mediated formation of melanin from tyrosine in the presence of the 3H-cocaine (3H
      COC), 3H-flunitrazepam (3H-FLU), and 3H-nicotine (3H-NIC) at 10-100,000 ng/mL.
      Polymerization in the presence of 10 or 100 ng/mL of each drug resulted in almost
      complete drug incorporation into the melanin pellet. Only 12% (3H-NIC) to 28% (3H
      FLU) of the pellet-associated radioactivity could be released upon treatment with
      6 M HCl. At 1000-100,000 ng/mL, between 20 and 50% of label became melanin
      associated. In each case a significant percentage of melanin-associated
      radioactivity was resistant to treatment with 6 M HCl. Nicotine-associated
      radioactivity in the polymer was subject to much greater quenching than was 3H
      COC or 3H-FLU, suggesting a much tighter association with the melanin. The
      subsequent demonstration of a covalent adduct of a melanin intermediate and
      nicotine has demonstrated the utility of this polymerization system as a model
      for further chemical characterization of drug-melanin interactions.

PMID- 11599609
TI  - Evaluation of an onsite alcohol testing device for use in postmortem forensic
      toxicology.
AB  - The disposable QED saliva alcohol test provides a very simple, fast, and reliable
      means for quantitative onsite alcohol detection. The purpose of this study was to
      determine if the QED test would be a useful tool for the determination of
      postmortem ethanol levels in cases where a rapid result was needed. QED results
      were compared with ethanol levels determined by headspace GC analysis. Both
      saliva and vitreous humor specimens were used for the evaluation. QED tests were
      initially attempted using the oral fluid from 50 individuals. Of these cases, 17
      of the tests were valid with 8 positive results. For 23 cases the oral fluid was
      not attainable, and for 10 cases, the sample was contaminated with blood making
      the tests invalid. The correlation between the oral fluid results and the blood
      headspace GC analysis was poor (r = 0.8345) over the range of 0.01-0.29 g/dL.
      Vitreous specimens were found to be the matrix of choice for analyzing postmortem
      cases using the QED. Only 6 of 171 specimens were found to be unsuitable. The QED
      results correlated well with the headspace GC analysis (r = 0.9931, n = 165).
      When using ethanol levels > 0.02 g/dL (n = 126), an average vitreous (GC)/blood
      ratio of 1.16 correlated well with the average QED/blood ratio of 1.22. Although
      the QED saliva alcohol test does not appear to be useful in determining
      postmortem saliva ethanol levels, it does provide accurate results when using
      postmortem vitreous humor as the testing matrix.

PMID- 11599610
TI  - Extraction of benzoylecgonine from urine specimens with Cerex Polycrom Clin II
      solid-phase extraction columns and the Speedisk Pressure Processor.
AB  - Benzoylecgonine (BZE) extraction from urine was explored using Cerex Polycrom
      Clin II solid-phase extraction (SPE) columns and the Speedisk 48 Pressure
      Processor as an alternative to the Prep1 automated sample processor and XTRX Type
      RP/W columns. Linearity for urine standards extracted using the Cerex-Speedisk
      method ranged from 20 to 3000 ng/mL. The mean recovery at the 100-ng/mL cutoff
      for three lots of columns was 92%. The mean of the within-run means for three
      batches, which had coefficients of variations of 1.8% or less, was 101.3 ng/mL at
      the 100-ng/mL cutoff level. Forty-six specimens known to contain BZE were
      analyzed by both the Prep1-Type RP/W and Cerex-Speedisk methods. The correlation
      for specimen BZE concentrations between the two methods gave an r2 of 0.9999 and
      a slope of 1.03. The Cerex-Speedisk system is an inexpensive alternative to the
      Prep1-Type RP/W system. It is less costly, requires little maintenance, has a
      small footprint, is hood compatible, and can process four times the number of
      specimens in a given time.

PMID- 11599611
TI  - Rapid detection of benzoylecgonine in vitreous humor by enzyme immunoassay.
AB  - The usual specimens submitted by a medical examiner for toxicological analysis
      include blood, urine, bile, vitreous humor, stomach contents, and solid-organ
      tissue. The detection of drugs in these specimens typically involves a
      combination of techniques including colorimetry, immunoassay, and gas
      chromatography. Although many laboratories rely principally on urine for the
      detection of drugs of abuse by immunoassay, these assays may be applied to other
      specimen types. An evaluation of Microgenics Corporation's cloned enzyme donor
      immunoassay (CEDIA) was conducted in order to evaluate its use in the detection
      of cocaine/cocaine metabolites in vitreous humor specimens. During a 14-month
      period, 392 vitreous humor specimens were analyzed by the CEDIA DAU Cocaine
      assay. Instrument parameters were set according to published manufacturer's
      guidelines. All presumptive positive immunoassay results prompted confirmatory
      testing and quantitation by gas chromatography-mass spectrometry (GC-MS) of other
      specimens including blood. Vitreous humor specimens were not tested by GC-MS.
      Using a approximately 100-ng/mL cutoff, the CEDIA assay produced 23 presumptive
      positive results, 22 of which were confirmed by GC-MS. The only specimen which
      could not be confirmed, elicited an immunoassay screen value near the cutoff
      limit. Routine analysis of blood, urine, bile, and/or bladder wash specimens by
      gas chromatography-nitrogen phosphorus detection revealed the presence of
      cocaine/cocaine metabolites in only 7 (31.8%) of the 22 confirmed cases. The
      concentration ranges of cocaine and benzoylecgonine in the blood specimens were
      none detected to 337 ng/mL and 17 to 8598 ng/mL, respectively. Cocaethylene was
      not detected in these cases. Analysis of vitreous humor specimens by CEDIA
      improved the detection rate of cocaine/cocaine metabolites by 0.7% in the cases
      submitted to our laboratory during the 14-month period.

PMID- 11599612
TI  - The detection of drugs of abuse in liquid perspiration.

PMID- 11599613
TI  - Ether: stability in preserved blood samples and a case of ether-assisted suicide.
AB  - Ethyl ether was detected in the blood of a deceased individual who had inhaled it
      from a mask while hanging himself. This case led to an investigation into the
      stability of ether in stored blood samples as described herein. Ether was spiked,
      at three concentrations, into batches of porcine blood. The blood was apportioned
      into grey-stoppered collection tubes and stored refrigerated until analysis. The
      concentration of ether in the blood was assessed at intervals over a two-month
      period. Analysis was performed by headspace gas chromatography. This study has
      shown, for a concentration range of 0.1 to 5.0 mg/mL, ether is stable in
      preserved, refrigerated blood for at least two months.

PMID- 11599614
TI  - A comprehensive screen for volatile organic compounds in biological fluids.
AB  - A headspace gas chromatographic (GC) screen for common volatile organic compounds
      in biological fluids is reported. Common GC phases, DB-1 and DB-WAX, with split
      injection provide separation and identification of more than 40 compounds in a
      single 20-min run. In addition, this method easily accommodates quantitation. The
      screen detects commonly encountered volatile compounds at levels below 4 mg%. A
      control mixture, providing qualitative and semiquantitative information, is
      described. For comparison, elution of the volatiles on a specialty phase, DB-624,
      is reported. This method is an expansion and modification of a screen that had
      been used for more than 20 years. During its first year of use, the expanded
      screen has proven to be advantageous in routine forensic casework.

PMID- 11599615
TI  - Urine analysis of laboratory personnel preparing cocaine training aids for a
      military working dog program.

PMID- 11599616
TI  - Citalopram distribution in postmortem cases.
AB  - This is a report of the analytical findings in 13 cases investigated by either
      the Office of the Chief Medical Examiner, State of Maryland or the Bexar County
      (San Antonio, TX) Medical Examiner's Office in which citalopram, a highly
      selective serotonin reuptake inhibitor used therapeutically as an antidepressant,
      was identified. In 8 of the 9 cases in which both blood and urine specimens were
      received, the urine citalopram concentration exceeded the blood concentration,
      indicating that urine is an appropriate specimen for screening citalopram use.
      The average liver to blood citalopram concentration ratio was 6.5 (range 3.1-13,
      n = 6). Three cases had blood concentrations less than 0.24 mg/L, which is in the
      reported antemortem therapeutic range of the drug. Eleven cases had blood
      concentrations less than 1.3 mg/L; in each of these cases, citalopram was
      determined to be an incidental finding to the ultimate cause of death.
      Quantitation of citalopram and the metabolite desmethylcitalopram in these cases
      yielded an average parent-to-metabolite ratio of 6.4.

PMID- 11599617
TI  - Fatalities caused by the MDMA-related drug paramethoxyamphetamine (PMA).
AB  - The past several years have seen a marked increase in the recreational use of 3,4
      methylenedioxymethamphetamine (MDMA) or "Ecstasy". MDMA use is especially common
      among young people participating in dance parties called "raves".
      Paramethoxyamphetamine (PMA) exhibits both structural and pharmacological
      similarity to MDMA. It may, however, be a more potent central stimulant,
      particularly in its effects on serotonergic transmission. Several fatalities from
      PMA have been reported in Australia, and here we report three recent fatalities
      that occurred in the midwestern United States in which each of the decedents
      believed that they were ingesting MDMA. Symptoms observed included agitation and
      bruxism, progressing to severe hyperthermia, convulsions, and hemorrhage. Blood
      was screened for drugs of abuse by enzyme immunoassay with the presence of
      amphetamines indicated in each case. Confirmation and quantitation for
      amphetamines was performed by gas chromatography-mass spectrometry. The deceased,
      two males ages 19 and 24 and a female age 18, had postmortem blood PMA
      concentrations of 1.07, 0.60, and 1.90 mg/L, respectively. PMA is not a
      contaminant of MDMA, and no MDMA was found in any of these cases. The primary
      metabolite of PMA is produced by O-demethylation to 4-hydroxyamphetamine, a
      reaction catalyzed by cytochrome P450 2D6. This enzyme is noted to be genetically
      polymorphic. Those with the "slow metabolizer" phenotype may be likely to have
      higher peak blood concentrations of PMA. Whether any of the decedents described
      herein were of the slow metabolizer phenotype is not known. Several groups have
      advocated the onsite use of the Marquis Test for the purpose of pill screening in
      efforts to distinguish PMA from MDMA. A dark purple is consistent with MDMA,
      whereas PMA imparts no color change in this test. PMA is often in the form of a
      white pill with a Mitsubishi symbol on one side. This design has been identified
      in at least one of these fatalities.

PMID- 11599618
TI  - Three cases of fatal paramethoxyamphetamine overdose.
AB  - Two recent cases of death due to paramethoxyamphetamine (PMA), a methoxylated
      phenylethylamine derivative, are described and compared with a previous PMA death
      that occurred in this province in 1985. The deceased were 18 or 19 years of age
      and were reported to have ingested either methylenedioxymethamphetamine (MDMA,
      Ecstasy) or methylenedioxyamphetamine (MDA) prior to their deaths. Concentrations
      of PMA were measured in both peripheral and heart blood samples using gas
      chromatography equipped with a nitrogen-phosphorus detector. PMA results in the
      most recent cases were 0.6 mg/L and 1.3 mg/L in the peripheral blood samples, and
      corresponding heart blood samples were 0.7 mg/L and 2.3 mg/L, respectively. In
      the 1985 case, the femoral blood concentration was 0.6 mg/L, and the heart blood
      concentration was 0.8 mg/L. Significant differences between heart and peripheral
      blood concentrations were observed in two of the three cases, which may indicate
      the potential for postmortem redistribution of PMA.

PMID- 11599619
TI  - A contemporaneous finding of fenproporex in a polydrug suicide.
AB  - Fenproporex is a sympathomimetic agent with a pharmacological profile similar to
      that of amphetamine. It is available in many countries throughout the world, but
      it is currently not available in the United States. Because of its stimulant
      effects, it has a great potential for abuse. To the best of our knowledge, there
      have been no literature reports of blood or serum concentrations found in
      therapeutic, toxic, or fatal cases. We report a case where fenproporex was a
      finding in the death of a young adult. Blood, urine, and gastric contents were
      analyzed. The following drug concentrations were found: 0.90 mg/L (inferior vena
      cava blood), 1.2 mg/L (urine), and 120 mg total (gastric) for fenproporex and
      0.084 mg/L (inferior vena cava blood), 0.94 mg/L (urine), and 0.14 mg total
      (gastric) for amphetamine. In addition to the fenproporex, other medications
      detected and their blood concentrations found in this case were H diazepam (0.54
      mg/L), nordiazepam (0.46 mg/L), diphenhydramine (0.12 mg/L), and gamma
      hydroxybutyric acid (GHB) (1100 mg/L).

PMID- 11599620
TI  - Applicability of opiate cutoffs to opiate intoxication cases.

PMID- 11599621
TI  - Vulvar cancer--(r)evolution in management.

PMID- 11599622
TI  - Vulvar cancer--what do we know about our patients?
AB  - INTRODUCTION: Vulvar cancer is uncommon in Singapore and to date there have been
      no local reports on this rare cancer. This is a descriptive study that aims to
      evaluate our patients' profiles, their management and their outcomes. MATERIALS
      AND METHODS: Between January 1981 and December 1998, there were 35 patients with
      vulvar cancer treated at KK Women's and Children's Hospital. The case records of
      these patients were reviewed. Survival was calculated using the Kaplan-Meier
      method. RESULTS: The modal age at diagnosis was 74.0 years (range 17.0-89.0
      years). Chinese patients accounted for 88% of the study group, Malays for 6%,
      Indians for 3% and other races made up 3% of the study group. The most common
      presenting symptom was an ulcer or lump (83.8%). Squamous cell carcinoma was the
      most common histological type (80.0%). Vulvar intraepithelial neoplasia III was
      found in 20% of the cases. There were five patients with other lower genital
      tract malignancies. Surgery was the most common treatment modality and wound
      breakdown was the most common complication. The overall five year survival was
      75.9%. For stage 1&2 disease, the five year survival was 90.0%. For stage 3&4
      disease, the five year survival was 26.0%. CONCLUSION: The rarity of vulvar
      cancer makes it best treated in a tertiary centre. There is a definite survival
      advantage in early diagnosis and treatment of vulvar cancer. Lymph node surgery
      was associated with a longer operating time and a higher chance of wound
      breakdown.

PMID- 11599623
TI  - Neurocysticercosis: a clinical and radiological appraisal from Kerala State,
      South India.
AB  - OBJECTIVES: Little has been published on Neurocysticercosis (NCC) in the State of
      Kerala, South India. This study was conducted to describe the clinical and
      radiological features of NCC in Kerala and also to study the frequency of NCC as
      seen in a tertiary referral setting. MATERIALS AND METHODS: We evaluated
      retrospectively 11 patients who were admitted with a diagnosis of NCC from 1986
      to 1998. A pre-abstracted proforma containing detailed demographic data, dietary
      habits, clinical features and history of travel outside Kerala and neuroimaging
      findings were obtained from patient records and the data was tabulated and
      analysed. Follow up assessment was made three months after treatment. RESULTS:
      There were a total of 11 patients, including nine males and two females in the
      age range of 24 to 62 years and a mean age of 35.2 years. All were nonvegans,
      only 36% were pork eaters while 18% claimed consumption of salads and uncooked
      vegetables. 55% of patients were migrants. Migrants were defined as those who
      lived outside the state of Kerala for more than six months. Seizure was the most
      common presenting complaint and occurred in all patients (100%). Multiple ring
      enhancing lesions were seen on computerised tomography (CT) and magnetic
      resonance imaging (MRI) scans in 60%. Calcified lesions were noted in two
      patients. An isolated instance of miliary or disseminated cysticercosis with
      subcutaneous nodules and multiple brain lesions in MRI scan was observed. All
      patients received anticysticercal therapy besides anticonvulsants. CONCLUSIONS:
      It appears that NCC is rather uncommon in Kerala. Better socioeconomic status,
      high literacy rate, improved sanitation and health care in the state of Kerala
      could be reasons for this observation. A prospective case-control study of NCC in
      Kerala is needed to study these factors.

PMID- 11599624
TI  - A comparison of male and female theft offenders remanded to a state psychiatric
      hospital.
AB  - We report a retrospective study examining the prevalence, demographic profile and
      pattern of psychiatric morbidity of theft offenders remanded for psychiatric
      assessment by the Singapore courts. Case records of 100 male and 100 female
      consecutively remanded theft offenders were reviewed. There was a high rate of
      psychopathology, with schizophrenia as the commonest disorder. Sex differences
      were identified in demographic profiles, psychiatric diagnoses, types of offences
      committed and likely psychiatric determinants of the offence. Depression was more
      common in females while substance abuse and antisocial personality disorder were
      diagnosed more frequently in males.

PMID- 11599625
TI  - Deep vein thrombosis in patients admitted for exacerbation of chronic obstructive
      pulmonary disease.
AB  - INTRODUCTION: There is a lack of data on the prevalence of deep vein thrombosis
      and pulmonary embolism in patients admitted to hospital for exacerbation of
      chronic obstructive pulmonary disease. Studies have found that most pulmonary
      embolism originate from deep vein thrombosis in the lower limbs, thus the
      prevalence of deep vein thrombosis may give an accurate reflection of the
      prevalence of pulmonary embolism. The aim of our study was to determine the
      prevalence of deep vein thrombosis in these patients, using duplex ultrasound of
      the lower limbs as the screening tool. METHODS: Thirty-three male patients
      admitted to the general ward for exacerbation of chronic obstructive pulmonary
      disease were screened for presence of deep vein thrombosis of the lower limbs
      using duplex ultrasound scan. RESULT: No patient in this study was found to have
      deep vein thrombosis of the lower limbs. CONCLUSIONS: The prevalence of deep vein
      thrombosis in local patients admitted for exacerbation of chronic obstructive
      pulmonary disease is likely to be low. We do not recommend the use of duplex
      ultrasound to screen for deep vein thrombosis in this group of patients.

PMID- 11599626
TI  - Swallowing problems in post irradiated NPC patients.
AB  - We present three patients with Nasopharyngeal Carcinoma (NPC) developing
      swallowing problems after radiotherapy as the primary modality of treatment. All
      patients had advanced stage NPC presenting with enlarged neck nodes and underwent
      radical external beam radiotherapy. All three patients had both CN X and CN XII
      palsies and had difficulty in both the oral and pharyngeal phases of swallowing.
      None of them has any clinical or radiological evidence of local recurrence in the
      post nasal space and neck or metastasis to the skull base. One patient underwent
      cricopharyngeal myotomy with epiglottopexy and hyoid suspension which failed and
      subsequently underwent laryngectomy. Another patient had medialisation
      thyroplasty and the third underwent a percutaneous endoscopic gastrostomy (PEG).

PMID- 11599627
TI  - Efficacy of a nitroimidazole containing tripletherapy regime in Singapore.
AB  - BACKGROUND: There has been a gradual increase in the proportion of Singapore
      patients with metronidazole resistant strains of Helicobacter pylori. We studied
      the efficacy of a nitroimidazole containing regime in eradicating H. pylori.
      METHODS: Consecutive treatment naive patients with peptic ulcer disease and
      culture proven H. pylori were recruited. From each patient, two antral biopsies
      were taken for rapid urease test and two for histology. Two biopsies each from
      the gastric antrum and corpus were taken for H. pylori culture. Antibiotic
      sensitivity to amoxycillin, metronidazole, clarithromycin and tetracycline were
      tested using the disc diffusion method. Patients were treated with lansoprazole
      30 mg bd, tinidazole 500 mg bd and clarithromycin 500 mg bd for seven days.
      Successful eradication was defined as either negative urea breath tests 4 and 12
      weeks after treatment, or negative histology and culture at least four weeks
      after the end of treatment. RESULTS: A total of 64 patients were culture positive
      (51 males, 13 females). Forty-two patients had duodenal ulcers (DU), 17 gastric
      ulcers (GU), and 5 DU and GU. Metronidazole resistance was detected in 16
      patients (25%). Three of the 16 patients (19%) had a mixed population of
      resistant and sensitive strains of H. pylori. None of the H. pylori isolates were
      resistant to amoxycillin, tetracycline or clarithromycin. Overall, eradication
      was achieved in 51/64 patients (80%). Eradication rate was 88% (42/48) among
      those with metronidazole sensitive strains, and 56% (9/16) among those with
      metronidazole resistant strains (p < 0.02). CONCLUSION: A high proportion of our
      patients with metronidazole resistant strains of H. pylori failed eradication
      therapy when a nitroimidazole containing regime was used. It may not be
      appropriate to use a nitroimidazole containing without prior knowledge of the
      antibiotic sensitivity pattern of the H. pylori isolate.

PMID- 11599628
TI  - A case report of a fractured healthytooth during use of Guedel oropharyngeal
      airway.
AB  - A young Chinese male with healthy dentition was admitted for haemorrhoidectomy.
      General anaesthesia was administered using facemask and a Guedel oropharyngeal
      airway with patient breathing spontaneously on nitrous oxide, oxygen, desflurane.
      Except for a brief episode of laryngospasm, no adverse events were noted
      intraoperatively. Postoperatively however patient was found to have a fractured
      upper incisor. Mechanism of possible events that caused the fracture are
      postulated. Problems associated with the use of Guedel airway are discussed and
      alternatives proposed.

PMID- 11599629
TI  - Paradoxical enlargement of tuberculous brain abscess during drug treatment: a
      case report.
AB  - This is a case report of a patient suffering from tuberculous (TB) brain
      abscesses. Despite supervised and appropriate anti-TB chemotherapy, the size of
      the abscesses paradoxically increased, accompanied by clinical deterioration at 1
      month. A second aspiration was performed which yielded a large amount of viable
      tubercle bacilli. The same drug regimen was continued. This was followed by
      complete resolution of the lesions in 12 months. Hence TB brain abscess which
      remains culture and smear positive after four weeks treatment may not represent
      treatment failure.

PMID- 11599630
TI  - Leopard syndrome.
AB  - The Leopard syndrome is a complex of multisystemic congenital abnormalities
      characterised by lentiginosis, electrocardiographic conduction abnormalities,
      ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation
      of growth and deafness (sensorineural). Hypertrophic cardiomyopathy, though not
      included in the mnemonic, is often associated. Although the Leopard syndrome is
      rare, it is important to recognise it since it can be associated with serious
      cardiac disease. It is advisable to follow up patients with Leopard syndrome for
      new onset of cardiac abnormalities and to monitor the progression of existing
      cardiac disease. We present a case report and review of the literature of this
      syndrome.

PMID- 11599631
TI  - Clinics in diagnostic imaging (63). Flipped bucket-handle tear of the lateral
      meniscus posterior horn.
AB  - Tears of the menisci in the knee are common after trauma, especially following
      sports injuries. A 21-year-old Chinese man with a flipped bucket-handle tear of
      the posterior horn of the lateral meniscus is reported. The MR imaging findings
      were confirmed at surgery. The classification and different types of meniscal
      tears, and the role of MR imaging in the diagnosis of meniscal lesions, are
      discussed.

PMID- 11599632
TI  - Benefits of treating hypertension in the elderly: should age affect treatment
      decisions?
AB  - Do the benefits of treating hypertension extend equally to all age groups,
      particularly the very elderly? Several large controlled trials have been
      published in recent years that confirm the benefits of the treatment of
      hypertension in terms of morbidity and mortality. However, these trials included
      only relatively small numbers of patients aged > or = 80 years. Data regarding
      such patients have been extracted and subjected to meta-analysis, but with
      inconclusive results. Further difficulties arise as a result of the range of
      therapeutic agents employed. Therefore, uncertainty still surrounds the value of
      treating very elderly patients with hypertension. The J-curve hypothesis, i.e.
      that a blood pressure threshold exists below which there is an increase in the
      rate of cardiac events, has been a concern in treating elderly patients. Upon
      close examination, this appears to be spurious. The Hypertension in the Very
      Elderly Trial study sets out to provide conclusive evidence for the benefits or
      otherwise of treating hypertension in the very elderly and has just commenced.
      The results of this trial will not be available for some time. In the meantime,
      should physicians initiate or continue treatment for very elderly individuals
      with hypertension? If so, what regimens should be employed and should target
      blood pressure levels be set? At the present time, it would appear sensible to
      provide treatment for very elderly patients with hypertension, particularly those
      with evidence of complications or target organ damage. In relatively healthy
      individuals with mild-to-moderate hypertension, the guiding principle should be
      'the lower the blood pressure the better'. Regarding the choice of therapeutic
      agent, a low-dose diuretic remains the first choice therapy.

PMID- 11599636
TI  - Equivalence classification by California sea lions using class-specific
      reinforcers.
AB  - The ability to group dissimilar stimuli into categories on the basis of common
      stimulus relations (stimulus equivalence) or common functional relations
      (functional equivalence) has been convincingly demonstrated in verbally competent
      subjects. However, there are investigations with verbally limited humans and with
      nonhuman animals that suggest that the formation and use of classification
      schemes based on equivalence does not depend on linguistic skills. The present
      investigation documented the ability of two California sea lions to classify
      stimuli into functional classes using a simple discrimination reversal procedure.
      Following the formation of functional classes in this context, the second
      experiment showed transfer of the relations that emerged between class members to
      a matching-to-sample procedure. The third experiment demonstrated that the
      functional classes could be expanded through traditionally defined equivalence
      relations. In these three experiments, appropriate within-class responding
      produced class-specific food reinforcers. Experiment 3 addressed the role of
      these reinforcers in equivalence classification and showed that the class
      specific reinforcers were sufficient to relate new stimuli to the functional
      classes. These findings show that sea lions can form equivalence classes in
      simple and conditional discrimination procedures, and that class-specific
      reinforcers can become equivalence class members.

PMID- 11599634
TI  - How well tolerated are lipid-lowering drugs?
AB  - It has been clearly established that lipid-lowering treatments [such as 3
      hydroxyl-3-methylglutamyl coenzyme A reductase inhibitors ('statins') or
      fibrates] can reduce cardiovascular events, and with one of the statins even
      total mortality, in high-risk populations. Intervention studies have not included
      the very old, but it is generally assumed that this patient group would benefit
      from these treatments to an extent similar to younger patients. Worries about the
      associations seen in observational studies between low cholesterol levels and
      cancer, cerebral haemorrhage or mood and behaviour change have been largely
      overcome by findings from the latest large drug intervention trials, which do not
      show any increase in these conditions with statin or fibrate treatments. The
      common adverse effects associated with these drugs are relatively mild and often
      transient in nature. Potentially more serious adverse effects, which are more
      clearly related to drug treatment and are probably dose-dependent, include
      elevations in hepatic transaminase levels and myopathy; however, these effects
      are uncommon and generally resolve rapidly when treatment is stopped. The risk of
      myopathy with fibrate treatment is increased in patients with renal impairment,
      and the risk of myopathy with statin treatment increases with co-administration
      of drugs that inhibit statin metabolism or transport. Other adverse effects are
      related to specific drugs, for example, clofibrate is associated with an
      increased risk of gallstones. Studies in elderly patients have not shown an
      increased risk of adverse effects with lipid-lowering drugs compared with younger
      patients, but in clinical practice there may be some increased risk, particularly
      with regards to drug interactions. Therefore, lipid-lowering drugs should be
      administered with extra caution to elderly patients.

PMID- 11599637
TI  - Second-order schedules of token reinforcement with pigeons: effects of fixed- and
      variable-ratio exchange schedules.
AB  - Pigeons' key pecks produced food under second-order schedules of token
      reinforcement, with light-emitting diodes serving as token reinforcers. In
      Experiment 1, tokens were earned according to a fixed-ratio 50 schedule and were
      exchanged for food according to either fixed-ratio or variable-ratio exchange
      schedules, with schedule type varied across conditions. In Experiment 2, schedule
      type was varied within sessions using a multiple schedule. In one component,
      tokens were earned according to a fixed-ratio 50 schedule and exchanged according
      to a variable-ratio schedule. In the other component, tokens were earned
      according to a variable-ratio 50 schedule and exchanged according to a fixed
      ratio schedule. In both experiments, the number of responses per exchange was
      varied parametrically across conditions, ranging from 50 to 400 responses.
      Response rates decreased systematically with increases in the fixed-ratio
      exchange schedules, but were much less affected by changes in the variable-ratio
      exchange schedules. Response rates were consistently higher under variable-ratio
      exchange schedules than tinder comparable fixed-ratio exchange schedules,
      especially at higher exchange ratios. These response-rate differences were due
      both to greater pre-ratio pausing and to lower local rates tinder the fixed-ratio
      exchange schedules. Local response rates increased with proximity to food under
      the higher fixed-ratio exchange schedules, indicative of discriminative control
      by the tokens.

PMID- 11599638
TI  - Response-independent milk delivery enhances persistence of pellet-reinforced
      lever pressing by rats.
AB  - If, during training, one stimulus is correlated with a higher rate of
      reinforcement than another, responding will be more resistant to extinction in
      the presence of that higher rate signal, even if many of the reinforcers have
      been presented independently of responding. For the present study we asked if the
      response-independent reinforcers must be the same as the response-dependent
      reinforcers to enhance the response's persistence. Twelve Long-Evans hooded rats
      obtained 45-mg food pellets by lever pressing (variable-interval 100-s schedules)
      in the presence of two discriminative stimuli (blinking vs. steady lights) that
      alternated every minute during daily sessions. Also, in the presence of one of
      the stimuli (counterbalanced across rats), the rats received additional response
      independent deliveries of sweetened condensed milk (a variable-time schedule).
      Extinction sessions were exactly like training sessions except that neither
      pellets nor milk were presented. Lever pressing was more resistant to extinction
      in the presence of the milk-correlated stimulus when (a) the size of the milk
      deliveries during training (under a variable-time 30 s schedule) was 0.04 ml (vs.
      0.01 ml) and (b) 120-s or 240-s blackouts separated components. Response
      independent reinforcers do not have to be the same as the response-dependent
      reinforcers to enhance persistence.

PMID- 11599639
TI  - Resistance to change of operant variation and repetition.
AB  - A multiple chained schedule was used to compare the relative resistance to change
      of variable and fixed four-peck response sequences in pigeons. In one terminal
      link, a response sequence produced food only if it occurred infrequently relative
      to 15 other response sequences (vary). In the other terminal link, a single
      response sequence produced food (repeat). Identical variable-interval schedules
      operated in the initial links. During baseline, lower response rates generally
      occurred in the vary initial link, and similar response and reinforcement rates
      occurred in each terminal link. Resistance of responding to prefeeding and three
      rates of response-independent food delivered during the intercomponent intervals
      then was compared between components. During each disruption condition, initial-
      and terminal-link response rates generally were more resistant in the vary
      component than in the repeat component. During the response-independent food
      conditions, terminal-link response rates were more resistant than initial-link
      response rates in each component, but this did not occur during prefeeding.
      Variation (in vary) and repetition (in repeat) both decreased during the response
      independent food conditions in the respective components, but with relatively
      greater disruption in repeat. These results extend earlier findings demonstrating
      that operant variation is more resistant to disruption than is operant repetition
      and suggest that theories of response strength, such as behavioral momentum
      theory, must consider factors other than reinforcement rate. The implications of
      the results for understanding operant response classes are discussed.

PMID- 11599633
TI  - Specific immunotherapy of cancer in elderly patients.
AB  - The concept of immunotherapy of cancer is more than a century old, but only
      recently have molecularly defined therapeutic approaches been developed. In this
      review, we focus on the most promising approach, active therapeutic vaccination.
      The identification of tumour antigens can now be accelerated by methods allowing
      the amplification of gene products selectively or preferentially transcribed in
      the tumour. However, determining the potential immunogenicity of such gene
      products remains a demanding task, since major histocompatibility complex (MHC)
      restriction of T cells implies that for any newly defined antigen, immunogenicity
      will have to be defined for any individual MHC haplotype. Tumour-derived peptides
      eluted from MHC molecules of tumour tissue are also a promising source of
      antigen. Tumour antigens are mostly of weak immunogenicity, because the vast
      majority are tumour-associated differentiation antigens already 'seen' by the
      patient's immune system. Effective therapeutic vaccination will thus require
      adjuvant support, possibly by new approaches to immunomodulation such as
      bispecific antibodies or antibody-cytokine fusion proteins. Tumour-specific
      antigens, which could be a more potent target for immunotherapy, mostly arise by
      point mutations and have the disadvantage of being not only tumour-specific, but
      also individual-specific. Therapeutic vaccination will probably focus on defined
      antigens offered as protein, peptide or nucleic acid. Irrespective of the form in
      which the antigen is applied, emphasis will be given to the activation of
      dendritic cells as professional antigen presenters. Dendritic cells may be loaded
      in vitro with antigen, or, alternatively, initiation of an immune response may be
      approached in vivo by vaccination with RNA or DNA, given as such or packed into
      attenuated bacteria. The importance of activation of T helper cells has only
      recently been taken into account in cancer vaccination. Activation of cytotoxic T
      cells is facilitated by the provision of T helper cell-derived cytokines. T
      helper cell-dependent recruitment of elements of non-adaptive defence, such as
      leucocytes, natural killer cells and monocytes, is of particular importance when
      the tumour has lost MHC class I expression. Barriers to successful therapeutic
      vaccination include: (i) the escape mechanisms developed by tumour cells in
      response to immune attack; (ii) tolerance or anergy of the evoked immune
      response; (iii) the theoretical possibility of provoking an autoimmune reaction
      by vaccination against tumour-associated antigens; and (iv) the advanced age of
      many patients, implying reduced responsiveness of the senescent immune system.

PMID- 11599640
TI  - Tolerance to the effects of cocaine on performance under behavior-correlated
      reinforcement magnitude.
AB  - Four pigeons responded under a fixed-interval 8-min schedule of food delivery in
      which the amount of food delivered at the end of each interval depended on
      performance during the interval (i.e., a correlated schedule). Specifically,
      duration of access to grain was contingent upon the number of responses made
      during the first 4 min of the interval. This differential outcome did not affect
      response rates or patterning relative to performance under a simple fixed
      interval 8-min schedule. Behavior under the correlated schedule was then
      investigated under doses of cocaine ranging from 0.3 to 10.0 mg/kg. A bitonic
      dose-response function was obtained for response rates and the time with head in
      the food hopper, whereas dose-dependent decreases were observed in the
      mathematical index of curvature (Fry, Kelleher, & Cook, 1960). The dose that
      produced the greatest increase in the head-in-hopper time was then administered
      prior to each session. Following repeated administration of cocaine, disruptions
      in response patterning were attenuated for all 4 pigeons; tolerance was also
      observed to the rate-increasing effects and increased head-in-hopper time for 2
      pigeons after chronic cocaine administration. Tolerance therefore developed
      despite the fact that the initial effect of cocaine was to increase the amount of
      food obtained.

PMID- 11599635
TI  - Role of free radicals in the neurodegenerative diseases: therapeutic implications
      for antioxidant treatment.
AB  - Free radicals and other so-called 'reactive species' are constantly produced in
      the brain in vivo. Some arise by 'accidents of chemistry', an example of which
      may be the leakage of electrons from the mitochondrial electron transport chain
      to generate superoxide radical (O2*-). Others are generated for useful purposes,
      such as the role of nitric oxide in neurotransmission and the production of O2*-
      by activated microglia. Because of its high ATP demand, the brain consumes O2
      rapidly, and is thus susceptible to interference with mitochondrial function,
      which can in turn lead to increased O2*- formation. The brain contains multiple
      antioxidant defences, of which the mitochondrial manganese-containing superoxide
      dismutase and reduced glutathione seem especially important. Iron is a powerful
      promoter of free radical damage, able to catalyse generation of highly reactive
      hydroxyl, alkoxyl and peroxyl radicals from hydrogen peroxide and lipid
      peroxides, respectively. Although most iron in the brain is stored in ferritin,
      'catalytic' iron is readily mobilised from injured brain tissue. Increased levels
      of oxidative damage to DNA, lipids and proteins have been detected by a range of
      assays in post-mortem tissues from patients with Parkinson's disease, Alzheimer's
      disease and amyotrophic lateral sclerosis, and at least some of these changes may
      occur early in disease progression. The accumulation and precipitation of
      proteins that occur in these diseases may be aggravated by oxidative damage, and
      may in turn cause more oxidative damage by interfering with the function of the
      proteasome. Indeed, it has been shown that proteasomal inhibition increases
      levels of oxidative damage not only to proteins but also to other biomolecules.
      Hence, there are many attempts to develop antioxidants that can cross the blood
      brain barrier and decrease oxidative damage. Natural antioxidants such as vitamin
      E (tocopherol), carotenoids and flavonoids do not readily enter the brain in the
      adult, and the lazaroid antioxidant tirilazad (U-74006F) appears to localise in
      the blood-brain barrier. Other antioxidants under development include modified
      spin traps and low molecular mass scavengers of O2*-. One possible source of lead
      compounds is the use of traditional remedies claimed to improve brain function.
      Little is known about the impact of dietary antioxidants upon the development and
      progression of neurodegenerative diseases, especially Alzheimer's disease.
      Several agents already in therapeutic use might exert some of their effects by
      antioxidant action, including selegiline (deprenyl), apomorphine and nitecapone.

PMID- 11599641
TI  - Area under the curve as a measure of discounting.
AB  - We describe a novel approach to the measurement of discounting based on
      calculating the area under the empirical discounting function. This approach
      avoids some of the problems associated with measures based on estimates of the
      parameters of theoretical discounting functions. The area measure may be easily
      calculated for both individual and group data collected using any of a variety of
      current delay and probability discounting procedures. The present approach is not
      intended as a substitute for theoretical discounting models. It is useful,
      however, to have a simple, univariate measure of discounting that is not tied to
      any specific theoretical framework.

PMID- 11599642
TI  - Treatment recommendations versus treatment realities: recognizing the rift and
      understanding the consequences.
AB  - Depression is a treatable disorder, although it often requires long-term therapy.
      To aid physicians in the effective long-term management of depression, treatment
      guidelines have been established by a number of organizations with minimum
      treatment duration recommendations. Unfortunately, numerous studies document a
      significant disparity between these recommendations and clinical practice
      realities. In particular, studies have shown that fewer than half of treated
      patients receive the recommended duration of 6 months of continuation therapy.
      Other clinical practice studies have reported that early discontinuation from
      therapy is associated with a substantial increase in the risk of relapse or
      recurrence. Long-term treatment of depression in clinical practice settings may
      benefit from a closer approximation to the conditions found in clinical trial
      settings.

PMID- 11599643
TI  - Factors affecting return of symptoms 1 year after treatment in a 62-week
      controlled study of fluoxetine in major depression.
AB  - BACKGROUND: In spite of impressive results in acute studies, the long-term
      treatment of major depression remains problematic. To explore the return of
      depressive symptoms and their interaction with social factors on long-term
      outcome, we assessed 55 patients whose depression had been treated during a 62
      week, fluoxetine maintenance study, 1 year after the study's termination. METHOD:
      During the year following the study termination, patients were free to select
      treatment options. Assessments at the 1-year follow-up included measures of
      depressive symptoms (using the Hamilton Rating Scale for Depression [HAM-D]),
      social and marital impairment (using the Weissman Social Adjustment Scale [SAS]),
      personal stressors (using the Holmes Social Readjustment Rating Scale), and
      history of treatment during the past year. RESULTS: At the time of the
      naturalistic follow-up, 53% of patients sustained their improvement in mood.
      Factors associated with return of depressive symptoms included personal stresses,
      marital maladjustment, personal decision to discontinue antidepressants, and
      medication failure. Psychosocial variables were associated with poor outcome in
      over 90% of impaired subjects. Development of subsyndromal symptoms during the 50
      week double-blind phase was predictive of poorer outcome at the long-term follow
      up. CONCLUSION: The study demonstrates that no matter how effective initial
      pharmacologic therapy may be, without ongoing clinical monitoring and support,
      particularly in dealing with issues such as marriage and handling significant
      life stresses, and compliance with medications, it will not be successful in the
      long-term treatment for a significant portion of patients with depression.

PMID- 11599644
TI  - Fluoxetine: a suitable long-term treatment.
AB  - A review of fluoxetine's safety profile, especially during long-term treatment,
      is presented. Key safety advantages for fluoxetine include lower adverse events
      and dropout rates compared with tricyclic antidepressants and other selective
      serotonin reuptake inhibitors (SSRIs), safety in overdose, and safe use in
      special population groups such as women in pregnancy. Prospectively ascertained
      pregnancy outcomes following exposure to SSRIs, mainly fluoxetine, consistently
      show no teratogenic effects as assessed in the postnatal period and in comparison
      with controls. An additional advantage of fluoxetine is the absence or mildness
      of discontinuation symptoms following treatment interruption, probably a
      consequence of fluoxetine's long half-life in comparison with other SSRIs. The
      available data on these topics confirm the suitability of long-term fluoxetine
      treatment.

PMID- 11599645
TI  - Compliance with antidepressants in a primary care setting, 1: Beyond lack of
      efficacy and adverse events.
AB  - BACKGROUND: Treatment guidelines recommend antidepressant treatment be continued
      for at least 6 months to ensure maximal improvement and to prevent relapse.
      Naturalistic studies show that the average length of treatment is shorter than 6
      months and that dropout rates are high. Factors leading patients to
      discontinuation of therapy are not well understood. This study investigates when
      and why patients stop treatment and whether they inform their doctors. METHOD:
      Patients (N = 272) receiving antidepressant therapy due to an episode of major
      depressive disorder (DSM-IV) were asked to complete an antidepressant compliance
      questionnaire. Patients were then telephoned monthly while they continued on
      antidepressant therapy, up to 6 months. During each call, patients were asked
      standard questions. RESULTS: By endpoint, 53% of patients had discontinued
      antidepressant treatment. The most common reason given was "feeling better."
      However, different dropout reasons were prevalent at different times after
      initiation of therapy. Overall, 24% of the patients did not inform their
      physician about stopping the antidepressant medication. The likelihood of
      patients' informing their physicians differed according to the patients' reasons
      for discontinuation and according to the patients' perceptions of their
      relationship with their physicians. CONCLUSION: These results provide new
      guidelines for improving compliance. Strategy should be adapted to the stage of
      treatment, as patients' reasons for discontinuation vary as treatment progresses.
      The attitude of the physician and the information provided by the physician
      significantly influence whether patients inform the physician when they
      discontinue antidepressant therapy.

PMID- 11599646
TI  - Compliance with antidepressants in a primary care setting, 2: the influence of
      gender and type of impairment.
AB  - BACKGROUND: DSM-IV diagnosis of major depressive disorder includes a requirement
      that symptoms result in significant clinical distress or impairment. This
      criterion is difficult to assess and is often overlooked. This study examines the
      use of the Sheehan Disability Scale as a possible method of assessing impairment,
      as well as the relationship between functioning and discontinuation of
      antidepressant medication. METHOD: Patients (N = 272) receiving antidepressant
      therapy due to an episode of major depressive disorder were asked to complete an
      antidepressant compliance questionnaire. Patients were telephoned monthly while
      they continued on antidepressant therapy, up to 6 months. During each call, the
      Sheehan Disability Scale was administered. RESULTS: Of patients referred to this
      study, 94.8% met DSM-IV criteria of at least 5 symptoms of major depressive
      disorder. Most patients had initial scores ranging from 5 to 8 on all 3 Sheehan
      disability subscales (occupational, social, and family functioning); 72% of
      patients had at least moderate impairment (scores > or = 4) on all 3 subscales.
      After 8 weeks of treatment, 42% of patients had scores < 4 on all 3 subscales
      (recovery); after 24 weeks, 64% of patients had scores < 4 on all 3 subscales.
      Dropout risk in men was related to improvement in occupational, social, and
      family functioning, whereas dropout risk in women was related only to improvement
      in family functioning. CONCLUSION: The Sheehan Disability Scale can be valuable
      in assessing impairment and thus in correctly diagnosing major depressive
      disorder. We suggest that scores of 4 or more (moderate impairment) on all 3
      subscales indicate sufficient impairment for a strict diagnosis of major
      depressive disorder. Functional symptoms continued to improve for up to 24 weeks
      on antidepressant therapy, suggesting 6 months or more of therapy is necessary
      for maximum functional improvement. Premature discontinuation of antidepressant
      therapy is more likely to occur in women who experience significant improvement
      in family functioning or men who experience significant improvement in any
      functional area.

PMID- 11599647
TI  - Exploring treatment alternatives: weekly dosing of fluoxetine for the
      continuation phase of major depressive disorder.
AB  - Antidepressant medications are typically taken on a daily basis owing to both
      tradition and the pharmacokinetics of these agents. Because fluoxetine and its
      primary metabolite norfluoxetine have long half-lives and flat dose-response
      curves, we examined the tolerability of a weekly dose and its equivalence to
      daily dosing during the continuation phase of treatment for major depressive
      disorder (MDD). Open-label treatment with 20 mg of fluoxetine daily for 7 weeks
      began with 114 subjects. Subsequently, 70 subjects who met criteria for response
      were randomly assigned in a double-blind design to 1 of 3 treatment groups (20 mg
      of fluoxetine daily [N = 21], 60 mg of fluoxetine weekly [N = 28], or placebo [N
      = 21]) and followed for 7 weeks. No statistically significant differences were
      observed in several clinical measures. Tolerability in the 3 groups was similar;
      there was no difference in dropout rates or adverse events. Hence, weekly dosing
      of fluoxetine appears to be well tolerated and possibly as effective as daily
      dosing in the treatment of MDD. It is proposed that less frequent dosing could
      potentially benefit patients by enhancing adherence and minimizing the risk of
      side effects and drug-drug interactions.

PMID- 11599648
TI  - Patient compliance with enteric-coated weekly fluoxetine during continuation
      treatment of major depressive disorder.
AB  - BACKGROUND: A once-weekly enteric-coated formulation of fluoxetine represents a
      new, effective option for the long-term treatment of clinically diagnosed
      depression. This study assessed compliance with the new once-weekly fluoxetine as
      compared with once-daily fluoxetine treatment. METHOD: Adult patients from the
      United Kingdom who had responded to fluoxetine treatment for a current episode of
      depression (DSM-IV criteria) were monitored for compliance with daily and weekly
      dose administration of fluoxetine. The study consisted of 2 study phases. Study
      phase I was a baseline assessment of 20 mg of fluoxetine daily dosing for 4 weeks
      (N = 117). The second phase of the study consisted of randomly assigning patients
      to either once-weekly (90 mg/wk) or once-daily (20 mg/day) fluoxetine for 3
      months (weekly, N = 56; daily, N = 53). Compliance with the dosing regimen was
      measured using an electronic Drug Exposure Monitor (eDEM, AARDEX Ltd., Zug,
      Switzerland). RESULTS: For those patients randomly assigned to weekly fluoxetine,
      compliance was 85.4% during study period I while on treatment with daily
      fluoxetine and then 87.5% while on treatment with weekly fluoxetine. This
      difference was not significant. For once-daily dosing, however, compliance
      declined from 87.3% during period I to 79.4% during period II (p < .001). After
      adjusting for compliance during study period I, weekly compliance during study
      period II was 87.8% and daily compliance was 79.0%, a statistically significant
      difference (p = .006). CONCLUSION: Compliance with once-weekly fluoxetine was
      better than that with once-daily fluoxetine. Compliance decreased over time when
      patients remained on daily dosing; however, when patients switched from daily
      dosing to weekly dosing, compliance did not decrease. The results of this study
      allay concerns about inferior compliance with a once-weekly regimen compared with
      the conventional once-daily regimen.

PMID- 11599649
TI  - Efficacy and safety of weekly treatment with enteric-coated fluoxetine in
      patients with major depressive disorder.
AB  - A new formulation of fluoxetine has been developed that is intended to allow for
      weekly dosing during the long-term treatment of depression. This 90-mg enteric
      coated formulation of fluoxetine was compared with 20-mg daily fluoxetine and
      placebo during a 25-week continuation treatment period in a study of 501
      depressed patients who had responded to acute treatment with 20-mg daily
      fluoxetine. Both active drug formulations were statistically superior to placebo
      in maintaining the acute treatment response and prolonging the time to relapse.
      Patients with high baseline anxiety responded similarly to the 90-mg weekly and
      20-mg daily fluoxetine treatments. In addition, the 90-mg weekly fluoxetine dose
      had a safety profile similar to that of both daily fluoxetine dosing and placebo.
      The once-weekly fluoxetine formulation provides an effective and tolerable
      treatment option for patients requiring extended depression therapy.

PMID- 11599650
TI  - The burden of recurrent depression: causes, consequences, and future prospects.
AB  - Depression represents one of the most profound human problems currently facing
      the global health care system. It is a prevalent clinical condition and is
      estimated to rival virtually every other known medical illness in burden of
      disease morbidity early in this millennium. Understanding the chronic nature of
      this illness is key to the development of a more informed, longitudinal
      perspective on the diagnosis and treatment of depression. In this report, the
      morbid impact of depression is reviewed, from the perspectives of illness
      symptoms, societal impact, and emerging evidence of critical neurobiological
      consequences of the untreated condition. Reconceptualizing major depression from
      this longitudinal and multidimensional perspective is crucial to providing an
      effective response to this critical public health challenge.

PMID- 11599651
TI  - Patient perspectives on once-weekly fluoxetine.
AB  - BACKGROUND: Continuation therapy is recommended for 4 to 9 months following
      remission of symptoms of major depressive disorder. Long-term maintenance therapy
      is recommended for patients with severe, recurrent symptoms. However, most
      patients do not complete an adequate course of therapy. We investigated patient
      perceptions of antidepressant dosing to determine whether weekly dosing could
      provide an additional tool to help more patients remain compliant with
      antidepressant treatment. METHOD: Physicians were asked to complete an anonymous
      patient profile for 7 patients currently receiving antidepressant treatment and
      to give those patients a questionnaire that the patients could submit
      anonymously. In addition, clinically depressed patients in the United States and
      in France were surveyed by telephone. RESULTS: Patients surveyed by questionnaire
      agreed most strongly with statements indicating that they would like their doctor
      to involve them in the choice of antidepressant medication, that they did not
      want others to know they were taking antidepressant medication, and that they
      disliked the idea of taking daily medication. Patients in the telephone survey
      agreed most strongly with statements indicating that they considered once-weekly
      dosing more convenient than daily dosing, that they believed taking 1 pill a week
      would make them feel less dependent on pills, and that they perceived more
      advantages than disadvantages in taking 1 pill a week. CONCLUSION: Weekly
      antidepressant treatment may provide an effective tool in helping patients with
      depression. Positive patient perceptions of weekly dosing suggest that some
      patients may remain on continuation or maintenance therapy longer when they have
      the option of weekly dosing.

PMID- 11599652
TI  - Functional foods, neutraceuticals, designer foods: innocent fad or
      counterproductive marketing ploy?

PMID- 11599653
TI  - Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors (statins).
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-reductase inhibitors (statins)
      are mainly considered for long-term use and often constitute part of a multiple
      drug regime. Besides common adverse drug effects, such as nausea, abdominal
      discomfort and headaches, all statins harbour the risk of myopathy and fatal
      rhabdomyolysis. Usually, the frequency of myopathy is low but the incidence
      increases during concomitant drug therapy. Statins do not differ in their
      pharmacodynamic property. Therefore, the differences in their pharmacokinetic
      profiles, i.e. affinity for metabolising enzymes, constitute the rationale for
      choosing a specific statin especially for combination therapy. In order to point
      out harmful combinations of therapeutics, this review summarises the
      pharmacokinetic data of six clinically used statins (atorvastatin, cerivastatin,
      fluvastatin, lovastatin, pravastatin and simvastatin) with special regard to
      metabolism and drug interactions. In summary, statins that lack a significant
      hepatic metabolism, i.e. pravastatin, or that are metabolised by more than one
      cytochrome P450 isoenzyme, i.e. fluvastatin, or whose metabolism is taken over by
      other cytochrome P450 isoenzymes in case of blockage of the main metabolising
      enzyme, i.e. cerivastatin, are the least prone to drug interactions.
      Nevertheless, in case of a specific concomitant drug therapy known to be
      associated with a higher risk of adverse events, i.e. cyclosporin A and statin,
      clinical symptoms of myopathy and biochemical data, such as increasing serum
      creatine phosphokinase, should be monitored carefully.

PMID- 11599654
TI  - Clinical pharmacology of thalidomide.
AB  - BACKGROUND: Thalidomide has a chiral centre, and the racemate of (R)- and (S)
      thalidomide was introduced as a sedative drug in the late 1950s. In 1961, it was
      withdrawn due to teratogenicity and neuropathy. There is now a growing clinical
      interest in thalidomide due to its unique anti-inflammatory and immunomodulatory
      effects. OBJECTIVE: To critically review pharmacokinetic studies and briefly
      review pharmacodynamic effects and studies of thalidomide in consideration of its
      chemical and stereochemical properties and metabolism. METHODS: Literature search
      and computer simulations of pharmacokinetics. RESULTS: Rational use of
      thalidomide is problematic due to lack of basic knowledge of its mechanism of
      action, effects of the separate enantiomers and metabolites and dose- and
      concentration-effect relationships. Due to its inhibition of tumour necrosis
      factor-alpha and angiogenesis, racemic thalidomide has been tested with good
      effect in a variety of skin and mucous membrane disorders, Crohn's disease, graft
      versus-host disease, complications to human immunodeficiency virus and, recently,
      in multiple myeloma. Adverse reactions are often related to the sedative effects.
      Irreversible toxic peripheral neuropathy and foetal malformations are serious
      complications that can be prevented. The results of several published
      pharmacokinetic studies can be questioned due to poor methodology and the use of
      non-stereospecific assays. The enantiomers of thalidomide undergo spontaneous
      hydrolysis and fast chiral interconversion at physiological pH. The oral
      bioavailability of thalidomide has not been unequivocally determined, but
      available data suggest that it is high. Absorption is slow, with a time to
      maximum plasma concentration of at least 2 h, and may also be dose-dependent;
      however, that of the separate enantiomers may be faster due to higher aqueous
      solubility. Estimation of the volume of distribution is complicated by probable
      hydrolysis and chiral inversion also in peripheral compartments. A value of
      around 11/kg is however plausible. Plasma protein binding is low with little
      difference between the enantiomers. Elimination of thalidomide is mainly by pH
      dependent spontaneous hydrolysis in all body fluids with an apparent mean
      clearance of 10 l/h for the (R)- and 21 l/h for the (S)-enantiomer in adult
      subjects. Blood concentrations of the (R)-enantiomer are consequently higher than
      those of the (S)-enantiomer at pseudoequilibrium. The mean elimination half-life
      of both enantiomers is 5 h. One hydroxylated metabolite has been found in low
      concentrations in the blood. Since both enzymatic metabolism and renal excretion
      play minor roles in the elimination of thalidomide, the risk of drug interactions
      seems to be low. CONCLUSIONS: The interest in and use of thalidomide is
      increasing due to its potential as an immunomodulating and antiangiogenic agent.
      The inter-individual variability in distribution and elimination is low. Apart
      from this, its use is complicated by the lack of knowledge of dose- or
      concentration-effect relationships, possible dose-dependent oral absorption and
      of course by its well-known serious adverse effects.

PMID- 11599655
TI  - Detailed characterization of experimentally derived human hepatic CYP1A1 activity
      and expression using differential inhibition of ethoxyresorufin O-deethylation by
      fluvoxamine.
AB  - OBJECTIVE: To characterize the distribution of mathematically derived human
      hepatic CYP1A1 activity using differential inhibition of ethoxyresorufin O
      deethylation (EROD) by fluvoxamine. METHODS: Quantitative CYP1A1- and CYP1A2
      mediated EROD activities were determined in 42 human livers using differential
      inhibition of EROD by fluvoxamine. CYP1A2-specific activity was also measured by
      phenacetin O-deethylation and caffeine 3-demethylation. Distributions of CYP1A1
      mediated EROD and CYP1-A2 probe activities were analyzed using cumulative
      distribution (probit) plots and the Kolgomorov-Smirnov test. Age effect on CYP1A1
      and CYP1A2-mediated EROD activities was evaluated using descriptive statistics
      and analysis of variance. RESULTS: The derived CYP1A1 protein concentration of
      0.58 +/- 1.04 pmol/mg was only 4% of the derived CYP1A2. Since CYP1A1 is
      intrinsically far more active than CYP1A2 in mediating EROD, contribution of
      CYP1A1 to EROD represented approximately 25-40% of CYP1A2 contribution. Three of
      the 42 livers exhibited no CYP1A1-mediated EROD. Approximately 8% of the
      individuals showed high CYP1A1 activity phenotype based on cumulative
      distribution curve analysis. Hepatic CYP1A1 activity was more variable than that
      of CYP1A2. The variance of CYP1A1-mediated EROD was significantly different from
      that of CYP1A2, using the Kolgomorov-Smirnov statistical test. Even though not
      statistically significant, an age-related pattern in CYP1A1-mediated activity was
      identified: activity was high in the pre-puberty group, then decreased in the
      young/mature adult group and, finally, a slight increase was observed in old age.
      CONCLUSIONS: Distribution pattern in CYP1A1-mediated EROD suggests that the low
      derived CYP1A1 expression is most likely induced rather than constitutive. CYP1A1
      activity deviates from log-normal distribution; the variations in hepatic CYP1A1
      activity may affect the conversion of procarcinogens to carcinogens. The age
      related trend in CYP1A1-mediated EROD activity hints that CYP1A1 responsiveness
      to inducers may change with age as well as with exposure to environmental
      inducers. These findings prompt (1) future genotyping studies to determine
      whether increased CYP1A1 inducibility is a result of genetic factors and (2)
      studies to address whether CYP1A1 inducibility changes with age.

PMID- 11599656
TI  - Pharmacokinetics of salicin after oral administration of a standardised willow
      bark extract.
AB  - OBJECTIVE: To evaluate the pharmacokinetics of salicin and its major metabolites
      in humans after oral administration of a chemically standardised willow bark
      extract. METHODS: Willow bark extract corresponding to 240 mg salicin (1,360 mg,
      838 micromol) was ingested by ten healthy volunteers in two equal doses at times
      0 h and 3 h. Over a period of 24 h, urine and serum levels of salicylic acid and
      its metabolites, i.e. gentisic acid and salicyluric acid, were determined using
      reverse-phase high-performance liquid chromatography. Renal excretion rate,
      elimination half-life and total bioavailability of salicylates were calculated.
      RESULTS: Salicylic acid was the major metabolite of salicin detected in the serum
      (86% of total salicylates), besides salicyluric acid (10%) and gentisic acid
      (4%). Peak levels were reached within less than 2 h after oral administration.
      Renal elimination occurred predominantly in the form of salicyluric acid. Peak
      serum levels of salicylic acid were on average 1.2 mg/l, and the observed area
      under the serum concentration time curve (AUC) of salicylic acid was equivalent
      to that expected from an intake of 87 mg acetylsalicylic acid. CONCLUSION: Willow
      bark extract in the current therapeutic dose leads to much lower serum salicylate
      levels than observed after analgesic doses of synthetic salicylates. The
      formation of salicylic acid alone is therefore unlikely to explain analgesic or
      anti-rheumatic effects of willow bark.

PMID- 11599657
TI  - Pharmacokinetics of cisplatin and relation to nephrotoxicity in paediatric
      patients.
AB  - BACKGROUND: Cisplatin is a highly effective and frequently used drug in the
      chemotherapy of solid tumours in children, but only limited data are available on
      the pharmacokinetics of cisplatin and its associated nephrotoxicity in paediatric
      patients. METHODS: We investigated the pharmacokinetics of free platinum (Pt) in
      12 children (25 courses) receiving cisplatin (75-120 mg/m2) either as a
      continuous 72-h infusion, prolonged single 6-h infusion or repetitive 1-h
      infusions. Plasma and urinary Pt concentrations were analysed using atomic
      absorption spectroscopy. Cisplatin-induced nephrotoxicity was determined using
      creatinine clearance and several glomerular and tubular marker proteins. RESULTS:
      Using a two-compartment model the pharmacokinetic parameters for free Pt were:
      initial half-life 21.6 +/- 9.6 min, terminal half-life 25.9 +/- 16.2 h, area
      under the plasma concentration-time curve (AUC) 13.5 +/- 4.97 (microg/ml) x
      h/(100 mg/m2) and cumulative renal elimination(infinity) 41.7 +/- 6.6% of dose.
      Higher cisplatin delivery rates led to higher peak concentrations of free Pt in
      plasma and urine and to lower cumulative renal Pt elimination (P < 0.01). During
      all courses, increases of urinary albumin and alpha1-microglobulin excretion were
      documented. The creatinine clearance decreased significantly to 70% of baseline
      values. Correlations were found between both peak free Pt concentrations in
      plasma and in urine and the maximum of urinary excretions of albumin and of N
      acetyl-beta-D-glucosaminidase and the nadir of the glomerular filtration rate (P
      < 0.05). CONCLUSIONS: With respect to nephrotoxicity, long-term infusions of
      cisplatin seem to be preferable over intermittent bolus administration in
      paediatric patients. The best predictive pharmacokinetic parameters for cisplatin
      associated nephrotoxicity in children are peak free Pt concentrations in plasma
      and urine.

PMID- 11599658
TI  - Independent patterns of cytochrome P450 gene expression in liver and blood in
      patients with suspected liver disease.
AB  - OBJECTIVE: Assessment of liver metabolism using blood samples was tested by
      comparison of cytochrome P450 (CYP) gene expression in paired liver and blood
      samples from 13 individuals. METHODS: Total RNA was isolated from percutaneous
      needle biopsies and blood collected simultaneously. Gene expression for CYP1A2,
      CYP1B1, CYP2E1 and CYP3A4 was studied using a real-time reverse-transcription
      polymerase chain reaction (RT-PCR) method. RESULTS: All CYP mRNA species were
      expressed in all liver biopsies but at varying levels. The highest and lowest
      levels of expression were observed for CYP2E1 and CYP1B1, respectively. The
      expression patterns differed between blood and liver. CYP1B1 was expressed in all
      blood samples at a 20% higher level than in the liver. CYP1A2, CYP2E1 and CYP3A4
      were expressed in blood at 35- to 5,000-fold lower levels than in liver. None of
      the transcripts in blood showed any correlation with the expression in liver.
      CONCLUSION: We conclude that blood cannot serve as a surrogate organ for
      assessment of the expression of the studied CYP genes in liver.

PMID- 11599659
TI  - Pharmacokinetics and pharmacodynamics of epoetin alfa once weekly and three times
      weekly.
AB  - OBJECTIVE: To compare the pharmacokinetics, pharmacodynamics, and tolerance of
      epoetin alfa administered subcutaneously (s.c.) once weekly (q.w.) and three
      times weekly (t.i.w.). METHODS: An open-label, randomized, parallel-design study
      was conducted in 36 healthy adults with hemoglobin (Hb) levels of 11.7 14.0 g/dl
      for women and 13.0-14.8 g/dl for men. Subjects were randomized to epoetin alfa
      150 IU/kg s.c. t.i.w. or 40,000 IU s.c. q.w. for 4 weeks. Serum erythropoietin
      concentrations were measured using a validated enzyme-linked immunosorbent assay
      (ELISA). Pharmacokinetic parameters [peak serum concentration (Cmax), mean
      predose trough concentration (Cmin), time to Cmax (tmax), clearance after s.c.
      administration (CL/F), area under the plasma concentration time curve (AUC), and
      terminal elimination half-life (t 1/2)] were calculated using model-independent
      methods. Mean changes from baseline and AUC of percentage reticulocytes, Hb, and
      total red blood cell (RBC) concentrations over the 1-month study period were
      calculated. RESULTS: The Cmax values for serum epoetin alfa q.w. were six times
      and AUC(0-168) values three times that of the t.i.w. regimen. Time profiles of
      changes in percentage reticulocytes, Hb, and total RBC over 1 month were similar
      between regimens. The rate of increase in Hb was similar for the two groups, and
      both groups exhibited a 3.1-g/dl increase in mean Hb levels from baseline through
      day 29. Changes in ferritin levels were generally similar between groups and
      reflected expected use of iron stores for Hb production. Epoetin alfa
      administered t.i.w. or q.w. was well tolerated and no serious adverse events
      occurred. CONCLUSION: The pharmacodynamic responses were equivalent between
      groups despite expected differences in total erythropoietin exposure. These
      results indicate that the epoetin alfa 150 IU/kg t.i.w. and 40,000 IU q.w.
      regimens can be considered clinically equivalent.

PMID- 11599660
TI  - Benzodiazepine use in an elderly community-dwelling population. Characteristics
      of users and factors associated with subsequent use.
AB  - OBJECTIVES: The objective of this study was to describe determinants of current
      and subsequent benzodiazepine use in an elderly population, the Paquid cohort.
      METHODS: The study was conducted on a cohort of 2,792 community-dwelling subjects
      65 years of age or more living in the Gironde department, southwestern France.
      Benzodiazepine use and its correlates were studied with data collected at
      inclusion in the cohort. Longitudinal analysis over a 5-year period of follow-up
      was done to identify baseline predictors of subsequent use. RESULTS: At baseline,
      prevalence rate of benzodiazepine use was 31.9%. It was associated with female
      gender [odds ratio (OR) = 2.0; 95% confidence interval (CI): 1.66, 2.46],
      previous psychiatric disease (OR = 2.87; 95% CI: 2.31, 3.56), concomitant
      antidepressant use (OR = 2.45; 95% CI: 1.59, 3.78), depressive symptomatology (OR
      = 1.70; 95% CI: 1.28, 2.26), multiple drug use (OR = 1.82; 95% CI: 1.50, 2.21),
      multiple chronic diseases (OR = 1.37; 95% CI: 1.12, 1.67) and poor self-perceived
      health (OR = 1.63; 95% CI: 1.33, 2.0). For the 1926 benzodiazepine non-users at
      inclusion and followed during 5 years, incidence rate of subsequent use was 5.37
      per 100 person-years (95% CI: 4.76, 5.98). In multivariate Cox proportional
      hazards regression analysis, previous psychiatric diseases, poor self-perceived
      life satisfaction and polymorbidity were significantly associated with subsequent
      benzodiazepine use. CONCLUSIONS: Elderly people are heavy users of
      benzodiazepines. Independently from mental health status, those in poor health
      were most at risk of benzodiazepine use.

PMID- 11599661
TI  - Levofloxacin-warfarin interaction.

PMID- 11599662
TI  - Improving prescribing during pregnancy and puerperium through educational
      efforts.

PMID- 11599663
TI  - Introducing Health Workers for Change: from transformation theory to health
      systems in developing countries.
AB  - This introductory paper provides the theoretical basis behind the Health Workers
      for Change methodology, and the role of interactive, participatory learning
      approaches in promoting social change. The methodology has its origins in Latin
      America and Kenya, where participatory research methods have been used widely to
      raise social consciousness and promote change. The paper discusses the resistance
      of health institutions to participatory ways of learning and the reasons why this
      occurs. It also presents the logic for the subsequent papers in this special
      issue and provides a summary of their respective contributions.

PMID- 11599664
TI  - Health Workers for Change: developing the initiative.
AB  - This paper describes an intervention developed in South Africa for health workers
      at the health facility level, and designed to explore interpersonal relations
      among health workers and between health workers and female clients. Several
      participatory methods to explore the provider-client relationship were tested
      with health workers. Health workers identified many constraints to the provision
      of adequate health services and that these constraints affected their work in
      general and their relationship with women clients in particular. Constraints
      included inadequacies and inefficiencies in management and the lack of gender
      sensitivity training. The participatory approach was found to be acceptable to
      the participants and effective in exploring interpersonal relationships.

PMID- 11599665
TI  - Health providers' opinions on provider-client relations: results of a multi
      country study to test Health Workers for Change.
AB  - A multi-centre study in four African countries was undertaken to test the
      acceptability and effectiveness of Health Workers for Change, a methodology to
      explore provider-client relations within a gender-sensitive context. This
      intervention addresses the interpersonal component of quality of care. The
      methodology, consisting of six workshops, was implemented by research teams in
      Zambia, Senegal, Mozambique and Uganda. It was found to be acceptable within in a
      range of cultural and primary health care settings. The workshops allowed
      difficult issues such as prejudice and bribery to be discussed openly, fostered
      problem solving and the development of practical plans to address problems that
      could strengthen district health systems.

PMID- 11599666
TI  - An evaluation of Health Workers for Change in seven settings: a useful management
      and health system development tool.
AB  - This paper presents the findings of a multi-centre study assessing the impact of
      Health Workers for Change (HWFC) workshops in seven different primary care sites,
      based on the common core protocol described in this paper. The paper discusses a
      common methodology used by the studies, consisting of a triangulation of
      qualitative and quantitative methods. Such methodologies are inherently complex
      as they require comparisons across systems, sites and procedures. The studies
      were conducted in six sites in Africa and one site in Argentina. Generally, the
      intervention resulted either in positive change or in no change, except in the
      area of staff relationships where conflicts were more frequent after the
      intervention than before. This may reflect a willingness to confront problems or
      contentious issues. Implementing the HWFC workshops improved provider-client
      relations, facility level functioning and aspects of staff interrelationships,
      and had some impact at the system level. All studies indicated that overall
      health system development is essential for improved service provision including
      quality of care. The findings also indicated that this intervention complemented
      and could assist health sector reform efforts and can play a role in sensitizing
      health workers to gender issues. The paper concludes with a discussion of the
      robustness of the methodology used in the studies.

PMID- 11599667
TI  - The health workers for change impact study in Kenya.
AB  - This paper reports the detailed results of a study of the impact of the Health
      Workers for Change (HWFC) workshop series on clients' perceptions of health
      services, relationships within the health centre and relations between the health
      facility and the district health system. The study was carried out in three
      stages: baseline, intervention and evaluation over a period of 20 months. Data,
      both qualitative and quantitative, were collected at three levels: client,
      facility and system. Results indicate that relations between health workers and
      clients improved a great deal after the intervention while those between the
      facility and the system remained to a large extent unchanged. The paper concludes
      that, with external support and help, especially from the health system level,
      health workers can work towards improving health services and their job
      satisfaction, which can lead to better health worker-client relations.

PMID- 11599668
TI  - An assessment of the impact of Health Workers for Change in Avellaneda, province
      of Buenos Aires, Argentina.
AB  - This paper describes the evaluation of the Health Workers for Change (HWFC)
      workshop series in a primary health care clinic in Avellaneda, Argentina. The
      study found that there was an important impact at the facility level 2 months
      after the intervention (T2). Health workers were motivated and willing to examine
      their own practices critically in an effort to improve quality of care.
      Informants from the community also perceived that patients were being treated
      more kindly. Eleven months later (T3), however, the impact at the facility level
      had receded significantly. At the system level the main benefit of the workshops
      was to focus attention on the health workers themselves, particularly their
      perception that there was little communication with the authorities. As a result,
      the number of system level supervisors increased and they were urged to spend
      more time in the clinics. Reasons for the limited impact at T3 are discussed and
      suggestions are made for improving the intervention.

PMID- 11599669
TI  - Health Workers for Change as a health systems management and development tool.
AB  - In this paper we draw overall conclusions concerning the Health Workers for
      Change (HWFC) methodology as a management and health systems development tool. We
      examine how HWFC has contributed to an elucidation of the four main themes with
      which this special Issue is concerned, namely: the value of participatory
      training; the need for gender sensitivity in health services; the impact of the
      HWFC intervention on gender sensitivity and quality of care in health services;
      and the ability to replicate the HWFC intervention in a variety of cultural and
      geographical sites. The paper concludes that HWFC is a useful health systems
      development tool, discusses other applications of HWFC beyond those reported in
      this Issue and makes several recommendations concerning its future use.

PMID- 11599670
TI  - The importance of gender in defining and improving quality of care: some
      conceptual issues.
AB  - This paper discusses some conceptual underpinnings of research on gender and
      quality of health services and demonstrates the importance of training health
      professionals about how gender influences the health-illness-care process in men
      and women. It addresses the need to provide opportunities for health providers to
      understand how gender influences their own lives and work. It also describes the
      gendered nature of the health system itself, an aspect that is little understood
      and hence neglected in the training of health workers and the planning and
      provision of services. The paper demonstrates the need for interventions such as
      Health Workers for Change to sensitize health workers to the needs of female
      clients in particular, but also to their own constraints and challenges as health
      workers. It is also meant to stimulate further research into these issues,
      particularly among resource poor populations.

PMID- 11599671
TI  - Obstetrician-gynecologist as primary care provider.
AB  - Obstetrics and gynecology is a unique field that combines preventive and primary
      care with female pelvic surgery and obstetrics. With the evolution of managed
      care, it has been a challenge to fit this field into the standard primary care
      paradigm. This article describes a 3-tiered, patient-oriented definition of
      primary care that encompasses the essential aspects of all primary care
      specialties, followed by a critical examination of how primary care specialties,
      including obstetrics and gynecology, fit into this definition. This approach
      suggests that to better meet the primary care needs of both patients and society,
      obstetrician-gynecologists must continue to improve their skills in preventive
      care, diagnosis and treatment of self-limited conditions, and diagnosis of
      serious nongynecologic conditions.

PMID- 11599672
TI  - The HCA National Disease Management Program for coronary disease detection and
      treatment in women.
AB  - The diagnosis and treatment of heart disease in women continues to be one of the
      greatest challenges facing cardiovascular medicine today. Marked reductions in
      mortality rates during the past 2 decades did not result in improved outcomes for
      women. A major rate-limiting step to improving mortality rates for women is early
      diagnosis and initiation of effective lifesaving therapies for women. In 1999,
      HCA Healthcare Systems, Inc, Nashville, TN, initiated a coordinated effort among
      208 hospitals in 26 states to improve the diagnosis of coronary disease and to
      target women who should receive aggressive risk factor modification and referral
      to cardiologists. We describe the initial phases of program development,
      including employee risk factor screening; citywide health risk assessment;
      nationwide educational programs for clinicians, staff, and consumers; and a
      dedicated outcomes assessment program for tracking women at risk for coronary
      disease. We believe that these efforts provide a venue for optimal care and
      improved outcomes for women served by HCA facilities.

PMID- 11599673
TI  - Relative costs of gynecologic endoscopy vs traditional surgery for treatment of
      abnormal uterine bleeding.
AB  - BACKGROUND: The traditional treatment for abnormal uterine bleeding when medical
      therapy fails has been abdominal or vaginal hysterectomy. More recently,
      operative gynecologic endoscopy (laparoscopy and hysteroscopy) has partially
      replaced this traditional approach. The cost and healthcare utilization of
      endoscopy compared with traditional surgical methods are poorly understood.
      OBJECTIVE: To compare the cost and healthcare utilization associated with
      different gynecologic endoscopic therapies vs traditional methods for the
      treatment of abnormal uterine bleeding. STUDY DESIGN: Review of the available
      medical literature. RESULTS: Vaginal hysterectomy is the least costly of all
      hysterectomy techniques. The direct costs of laparoscopically assisted vaginal
      hysterectomy are higher than those of abdominal hysterectomy, but the indirect
      costs are significantly less. The direct and indirect costs of endometrial
      ablation/resection are significantly lower than those of hysterectomy even when
      the cost of treatment failures is included. CONCLUSION: Endometrial
      ablation/resection might be chosen over hysterectomy to treat abnormal uterine
      bleeding because it avoids major surgery, significantly shortens hospitalization,
      and allows rapid return to normal functioning.

PMID- 11599674
TI  - Factors associated with healthcare costs in women with fibromyalgia.
AB  - OBJECTIVE: To examine how women with high and low healthcare costs differ by
      using the Anderson Health Behavior Model of Utilization as a theoretical
      framework. STUDY DESIGN: One-year longitudinal design. PATIENTS AND METHODS: A
      total of 537 female health maintenance organization members with fibromyalgia
      participating in a study examining the effects of social support and education on
      health status and healthcare use were divided into 2 groups using a median split
      on health costs. Predisposing variables (demographic variables, self-efficacy,
      depression, and social support), enabling characteristics (income), and need
      variables (health status, perceived health status, disease severity, duration of
      symptoms, and comorbidity) were measured. Patients completed a battery of
      questionnaires at baseline assessment, and healthcare costs were assessed 1 year
      before and 1 year after baseline assessment. Healthcare data were collected from
      medical records. Healthcare costs were estimated by multiplying the number of
      each type of healthcare contact by the most recent national average cost figures.
      RESULTS: Multivariate analysis of covariance controlling for costs during the
      year before baseline assessment was performed. Low-cost patients had fewer
      comorbid conditions, better health status, higher self-perceived health status,
      less disease severity, greater self-efficacy for functioning, lower depression
      scores, and higher social support scores. Chi2 analyses revealed no significant
      differences between groups on marital status but a significant difference in
      income: low-cost patients were more likely to report higher incomes. CONCLUSIONS:
      There were several significant differences between people with higher and lower
      healthcare costs. Although effect sizes were small, many variables may be
      responsive to intervention.

PMID- 11599675
TI  - Evaluation and treatment of postmenopausal osteoporosis.
AB  - Osteoporosis is a prevalent condition among elderly women and is associated with
      an increased risk for fractures. With the burgeoning size of the elderly
      population, a practitioner is likely to face many questions regarding the
      evaluation and management of postmenopausal osteoporosis. This review discusses
      and compares available therapies. All women should have adequate calcium and
      vitamin D intake. Women diagnosed as having osteoporosis should be evaluated for
      secondary causes of osteoporosis and risk factors for falls. For women with
      postmenopausal osteoporosis, therapy with hormone replacement, bisphosphonates
      (alendronate sodium or risedronate sodium), raloxifene hydrochloride, or
      calcitonin should be considered. The results of ongoing studies will help refine
      the strategies used for management of postmenopausal osteoporosis.

PMID- 11599676
TI  - Outbreak of osteodystrophia fibrosa in young goats.
AB  - Osteodystrophia fibrosa was diagnosed in young goats which received a dict of 60%
      wheat straw and 40% barley for 8 months. The ratio of calcium:phosphorus in the
      diet was 1:1.8. The clinical signs were bilateral and symmetrical enlargement of
      the face, swelling of the joints, and limb deformities. The laboratory findings
      showed a low level of serum calcium in all affected goats. Histopathological
      examination revealed marked fibrous deposition and osteoclasia in bones of the
      maxilla and mandible.

PMID- 11599677
TI  - Primary intranasal transmissible venereal tumour in the dog: a retrospective
      study of six spontaneous cases.
AB  - The medical records of six dogs with primary intranasal transmissible venereal
      tumour (TVT) were reviewed. Epistaxis (4/6), serosangineous nasal discharge
      (2/6), oronasal fistulae (2/6), facial swelling (1/6) and submandibular
      lymphadenopathy (3/6) due to reactive hyperplasia (2/3) and metastasis (1/3) were
      the most common complaints and clinical findings. Diagnosis was made by
      rhinoscopy and confirmed by cytology and histopathology in five dogs and by
      cytology only in one dog. The microscopic appearance of the tumours with both
      diagnostic techniques was typical of TVT. Four cases were treated effectively
      with four to five weekly cycles of vincristine monotherapy that resulted in
      complete resolution of TVT masses in approximately 1 month. One case was
      resistant to this kind of treatment and another one was lost to follow-up.

PMID- 11599678
TI  - Recovery times and evaluation of clinical hemodynamic parameters of sevoflurane,
      isoflurane and halothane anaesthesia in mongrel dogs.
AB  - In the present study the influence of three volatile agents (halothane,
      isoflurane and sevoflurane) in oxygen at two concentrations [1.5 and 2 minimum
      alveolar concentration (MAC)] on non-invasive cardio-respiratory parameters
      (heart and respirators rates, non-invasive blood pressures at 15, 30, 60 min and
      after extubation) and on the recovery times (appearance of the first eyelid
      reflex, emergence time) after clinical anaesthesia was studied. After
      premedication with fentanyl-droperidol (5 microg/kg and 0.25 mg/kg,
      intramuscularly) and induction with propofol (5 mg/kg, intravenously) six dogs
      were randomly anaesthetized for 1 h for a standard neurologic stimulation test. A
      wide individual variation in respiration rate (induced by an initial hyperpnea)
      was observed in the 1.5 MAC protocols, without significant differences. Heart
      rate was significantly lower during 1.5 and 2 MAC halothane when compared to
      isoflurane and sevoflurane. An increase from 1.5 to 2 MAC induced significant
      decreases in diastolic (DAP) and mean arterial blood pressure in all groups
      without significant changes in the systolic arterial pressures. Only DAP in
      sevoflurane protocol was significantly different at 1.5 and 2 MAC compared to
      halothane. Time had no significant influences in the non-invasive blood pressures
      in all protocols. Extubation induced a significant increase of all parameters in
      all protocols. The time for a first eyelid reflex was significantly longer after
      2 MAC compared to the 1.5 MAC protocol. There was no significant difference
      between the three anaesthetic agents. Although emergence time was longest for
      halothane at both anaesthetic concentrations, no significant difference in
      emergence time was observed for the three volatile agents.

PMID- 11599679
TI  - Use of the flexion test of the distal forelimb in the sound horse: repeatability
      and effect of age, gender, weight, height and fetlock joint range of motion.
AB  - The flexion test of the distal limb is a commonly used clinical tool in both lame
      and sound horses. In the latter use it is given some predictive value. In recent
      studies it has been shown that examiner-related factors (force, time) may
      strongly influence the outcome of the test. In the present study, the possible
      influences of a number of horse-related factors and short- and long-term
      repeatability were investigated. Flexion tests were performed by the same
      researcher in 100 clinically sound horses under standardized conditions. The
      outcome of the test was scored on a 9-point semiquantitative scale. The maximum
      flexion angles of the fetlock joints were measured and the range of motion (ROM)
      of the fetlock joint was calculated. In the second part of the study, flexion
      tests were repeated, at intervals of 10 min, 30 min, 48 h and 6 months in 23
      horses to assess repeatability. Over 60% of the 100 sound horses had a positive
      flexion test. Of these, about 50% showed a slight lameness, 35% a mild lameness,
      and 15% a distinct lameness. There was no influence of weight, height or ROM on
      the score of the flexion test. The outcome of the flexion test increased
      significantly with age and was significantly higher in mares than in geldings.
      When repeating the flexion test with short intervals of 10 and 30 min, the score
      increased significantly after the second test. Repeated flexion after 48 h did
      not result in a significantly different outcome. Over a 6-month period, the
      outcome of the test decreased significantly and the ROM increased significantly.
      It is concluded that most clinically sound horses have a (slightly) positive
      flexion test of the distal limb. This and the lack of long-term consistency of
      the test cast doubt on the presumption that a positive flexion test may be an
      indication for subclinical joint disorders and question the possible value of the
      test as a predictor of future joint-related problems. There exists a wide
      individual variation in ROM of the fetlock joint with, in sound horses, no
      relationship between ROM and the outcome of the flexion test. The factors age and
      gender should be taken into account when interpreting the results of a flexion
      test.

PMID- 11599680
TI  - Long-term observation of subclinical chronic copper poisoning in two sheep
      breeds.
AB  - Fourteen castrated male sheep of two breeds, the Mutton Merino (MMB) and
      Blackhead Suffolk cross breed (BSC), were exposed to an oral copper (Cu) intake
      of 3.7 mg/day per kg body weight for 84 days (high Cu group, HCu), and 11
      castrated male sheep received a daily oral Cu intake of 0.16 mg/day per kg body
      weight (controls). Liver Cu concentration was measured in liver biopsies until
      2.7 years after Cu overdose. Haematologic parameters, plasma Cu, enzymes and
      metabolites were analysed and post-mortem examinations were carried out. No
      haemolytic crises occurred. The highest liver Cu concentrations (133-677 mg/kg
      wet weight) were measured in HCu sheep around day 110 with significantly higher
      values in BSC than in MMB. The very slow decreases of liver Cu concentration of
      HCu sheep after day 215 showed individual half-life periods of 175 +/- 91 days. A
      progressive Cu retention in the liver of HCu sheep during Cu supplementation
      indicates strong Cu binding and storage in the liver. High values of glutamate
      dehydrogenase (20-940 U/l) measured frequently until day 700 and a diminished
      plasma clearance of bromosulphthalein as well as pathohistological findings of
      focal liver necrosis confirm the markedly chronic character of Cu poisoning.

PMID- 11599681
TI  - Immunoperoxidase and histopathological examinations of leptospiral nephritis in
      cattle.
AB  - This study was designed to investigate the role of leptospirae in interstitial
      nephritis. Sixty-eight white-spotted kidneys and 30 grossly normal kidneys from
      slaughtered cattle were examined histologically and immunohistochemically for the
      presence of Leptospira interrogans antigens. The presence of L. interrogans
      antigens was found in 21 of 68 white-spotted kidneys and in four of 30 normal
      kidneys. In conclusion, the detected incidence of infection with L. interrogans
      was not high, but there was a relationship between the presence of interstitial
      nephritis and leptospiral antigens.

PMID- 11599682
TI  - Mortality trend for multiple sclerosis in Italy (1974-1993).
AB  - The prevalence of multiple sclerosis (MS) in Italy is one of the highest in
      Europe, estimated proportions ranging between 32 and 69 cases per 100,000. An
      update of mortality time trend analyses can help trace a picture of the evolution
      of the disease and contribute to the interpretation of differences related to
      latitude and gender. Standardized mortality ratios (SMR) were computed for the
      1974-1993 calendar period, using the pooled data set as standard. World
      population was the standard used to estimate age-adjusted rates for all Italy,
      while for selected regions the 1991 Italian population was utilized. Time trend
      analysis was performed using the Poisson regression model and the variation of
      mortality rates in time was expressed as mean difference per cent per year. Age
      adjusted rates per million inhabitants were 4.1 for males and 5.0 for females.
      Northern Italian regions showed higher MS mortality rates than Central and
      Southern regions and Sicily, particularly in females; the effect was less evident
      in Sardinia. Time trend analysis by area showed a mortality decrease in Northern
      Italy (-1.15%) that reached statistical significance for men. In central regions
      a slight increase of borderline statistical significance (+1.03%) was observed
      only in women. while in the South and Sicily a statistically significant increase
      was seen in both males (+2.14%) and females (+3.09%). The analysis of the time
      trend for all Italy did not reveal significant variations in male mortality; by
      contrast, a slight, but statistically significant, increase (+0.88%) was observed
      in female mortality. Analysis of age-adjusted MS mortality rates in each region
      suggested the presence of an effect due to latitude. The occurrence of an
      increasing trend in Southern Italian regions and Sicily deserves further
      investigation.

PMID- 11599683
TI  - Role of the coypu (Myocastor coypus) in the epidemiology of leptospirosis in
      domestic animals and humans in France.
AB  - The coypu (Myocastor coypus), a rodent whose natural habitat is stagnant
      freshwater, has become a widespread pest in France within the last decade. This
      study investigated the prevalence of seropositivity and the renal carriage of
      leptospires in coypus in order to evaluate their role in terms of the risk of
      infection by Leptospira interrogans in domestic animals and humans. The study
      involved the application of serological and bacteriological methods to identify
      leptospires infection and/or carriage in 738 coypus trapped from 1996 to 1999 in
      six areas of France. Seroprevalence in samples ranged from 16.5 to 66%, and three
      field strains were isolated (two L. interrogans Icterohaemorrhagiae and one L.
      interrogans Sejroe). This first report on the isolation of leptospires from
      coypus in France emphasises the role of this animal in the epidemiology of
      leptospirosis.

PMID- 11599684
TI  - Screening for tuberculosis upon admission to shelters and free-meal services.
AB  - BACKGROUND: The homeless are at very high risk of suffering tuberculosis (TB).
      The aims of this study were to determine the prevalence and risk factors for
      tuberculosis infection and disease among the homeless in Barcelona and to
      evaluate the roles of case finding and contact investigation. METHODS:
      Observational prevalence study carried out between 1997 and 1998. PARTICIPANTS:
      447 homeless patients (394 men and 53 women) were evaluated before admission to
      shelters and free-meal services. At the same time, 48 co-residents with smear
      positive TB patients in 2 long-term shelters were evaluated too. A chest X-ray
      and Tuberculin Skin Test were performed on all subjects. Sputum smears were
      processed by the Ziehl-Neelsen and Lowenstein-Jensen procedures in patients with
      radiographic findings consistent with pulmonary TB. RESULTS: Of the 447 homeless
      examined, 335 (75%) were infected with Mycobacterium tuberculosis. Active
      pulmonary TB was diagnosed in five persons (1.11%), and 62 (13.8%) had
      radiographic evidence of inactive pulmonary TB. Tuberculosis infection was
      associated with age and smoking, but not with sex or alcohol abuse. No
      significant differences in infection rates were found between the main group and
      48 homeless co-residents of smear-positive subjects. Only 16.9% of the homeless
      with active TB in Barcelona in the same period were diagnosed through active case
      finding, the remainder being mainly detected in hospitals (69.8%) and other
      several centres (13.3%). CONCLUSIONS: Homeless individuals have a very high risk
      of TB infection and disease and contact investigation requires specific methods
      for them. Programmes of screening and supervised treatment should be ensured in
      this group.

PMID- 11599685
TI  - Seasonal variations in dietary intake affect the consistency of dietary
      assessment.
AB  - BACKGROUND: Nutritional epidemiology studies are usually based on one dietary
      assessment without taking into account the season in which the interview is taken
      or adjusting for the difference in reporting dietary intake in different seasons.
      The semiquantitative food frequency questionnaire has become the primary
      questionnaire method for measuring dietary intake in epidemiological studies. The
      aims of this report were (a) to evaluate the effect of season on dietary intake
      as measured by a semiquantitative food frequency questionnaire (FFQ) conducted
      twice: once in summer and a second time in winter; and (b) to assess the effect
      of the differences in dietary intake on biochemical and anthropometric seasonal
      related changes, such as serum cholesterol and body mass index (BMI). POPULATION
      AND METHODS: The study population consisted of 94 male industrial employees who
      participated in clinical biochemical and physical examinations as well as
      evaluation of their dietary intake twice a year. Dietary intake was assessed
      using the semiquantitative FFQ that included 96 items and was conducted by a
      personal interview. RESULTS: We found a significant increase in the intake of
      selected nutrients in winter as compared to summer as well as an increased intake
      of animal fat-containing foods such as meat and dairy products. Significant
      correlation coefficients were shown between the increase in dietary intake of
      saturated fat and the increase in BMI, serum total and LDL cholesterol. The
      increase in dietary cholesterol was significantly and positively correlated with
      the increase in serum total and LDL cholesterol. CONCLUSION: Although FFQ are
      designed to assess average yearly food intake, we identified significant seasonal
      changes in dietary intake as measured by FFQ. These changes have a health impact
      on our population.

PMID- 11599687
TI  - Age-specific seroepidemiology of hepatitis A, B, and E infections among children
      in Istanbul, Turkey.
AB  - This study was performed for evaluation of seroprevalence of hepatitis A, B, and
      E among children in Istanbul, Turkey. The study group included 909 children who
      were 6 months-15 years of age. The children were separated to three age groups:
      Group 1 (6 months-4.9 years; n = 321), Group 2 (5.0-9.9 years; n = 318), and
      Group 3 (10.0-15.0 years; n = 270). Group I was divided to two subgroups for
      evaluation of the maternal antibody sera (6 months-2 years and over 2 years).
      Serum IgG anti-HAV, anti-HBc, and anti-HEV were tested by commercial ELISA kits.
      The data were studied by multivariant analysis. In all subjects, seroprevalence
      of hepatitis A, B, and E were determined as 29, 15.9, and 2.1% respectively. The
      prevalence of hepatitis A increased with age (p < 0.05; Group 1 15.1% and Group 3
      49.6%). Anti-HBc IgG level did not significantly change with age (Group 1 18.6%
      and Group 3 15.4%; p > 0.05). The seroprevalence of hepatitis E virus infection
      was higher in Group 1 (3.7%) than Group 3 (0.3%; p < 0.05). In Group 1 first
      subgroup, between 6 month and 2 year, antibody levels were 12.2, 17.3, and 4.8%
      respectively, for anti-HAV IgG, anti-HBc IgG and anti-HEV IgG. Hepatitis A and B
      infection is a community health problem, but hepatitis E infection is low in
      children in Istanbul, Turkey. The high positive rate in Group I for IgG anti-HEV
      may be due to maternal antibodies.

PMID- 11599686
TI  - Increased immunogenicity of the MF59-adjuvanted influenza vaccine compared to a
      conventional subunit vaccine in elderly subjects.
AB  - Three-hundred and eight outpatient elderly subjects (> or = 65 years) were
      randomly assigned to receive the MF59-adjuvanted influenza vaccine (FLU-AD; n =
      204) or a conventional subunit influenza vaccine (AGRIPPAL S1; n = 104) in order
      to compare the safety and immunogenicity of the two vaccines. Although mild pain
      at the injection site was reported more frequently by subjects immunised with the
      adjuvanted vaccine, both vaccines were shown to be safe and well tolerated. The
      adjuvanted vaccine was more immunogenic as indicated by higher post-immunisation
      geometric mean titres (GMTs) and by higher proportions of subjects with post
      immunisation > or = four fold increases of antibody titres or subjects with > or
      = 1/160 post-immunisation HI titres. These differences, statistically significant
      for all three strains after immunisation, indicated that, by addition of the MF59
      adjuvant emulsion, conventional subunit influenza antigens acquire an enhanced
      immunogenicity without any clinically significant increase of their
      reactogenicity.

PMID- 11599688
TI  - Immunogenicity of a recombinant hepatitis B vaccine (Euvax-B) in haemodialysis
      patients and staff.
AB  - Hepatitis B vaccine is the most effective strategy for preventing the
      transmission of hepatitis B virus (HBV) in haemodialysis centers. Nevertheless,
      lower vaccine responses have been reported in haemodialysis patients as compared
      with healthy subjects. This study examines the response to Euvax-B in Brazilian
      haemodialysis patients and staff. A total of 102 eligible patients (n = 42) and
      staff members (n = 60) consented to be studied. Patients were immunized
      intramuscularly with four doses of 40 microg of Euvax-B vaccine at 0, 1, 2 and 6
      months. In staff members, the vaccine was administered in three doses of 20
      microg at 0, 1, and 6 months. Post-vaccine samples were taken from all subjects I
      month after each dose. The vaccine response was determined by measuring antibody
      to the hepatitis B surface antigen (anti-HBs) levels using ELISA. Subjects with
      anti-HBs titres equal to or higher than 10 UI/L were considered immune protected.
      Of the haemodialysis patients who received four doses of hepatitis B vaccine,
      89.5% responded to Euvax-B vaccine. The geometric mean of anti-HBs titres was
      322.8 IU/L (95% CI: 317.7-328). Among staff members, 93.3% reached anti-HBs
      protective titres after the third vaccine dose. The geometric mean of anti-HBs
      titres was 2,209 IU/L (Cl: 2,198-2,219). Age, male gender and body mass index
      were not associated with vaccine response in either group. This study showed a
      good immunogenicity response to Euvax-B in haemodialysis patients and staff.

PMID- 11599689
TI  - Assessment of long-term efficacy of hepatitis B vaccine.
AB  - In a healthy cohort of 462 subjects in which hepatitis B vaccine was administered
      between 1990 and 1992 a follow-up study was carried out to determine the duration
      of protection. Individuals with antibody against the hepatitis B virus surface
      antigen (anti-HBs) titer lower than 100 mIU/ml were administered a booster dose
      and antibodies determined 30 days later. The proportion of protection 6.5 years
      after vaccination was 85% (95% CI: 82-88). Only nine vaccinees seroconverted to
      anti-HBc positivity without becoming carrier or ill. In 125 subjects in which a
      booster dose was administered a significant increase in geometric mean of anti
      HBs titer was observed (609 mIU/ml) as compared to late (13 mlU/ ml) and early
      post-vaccination antibody levels (256 mIU/ml, Wilcoxon's test, p < 0.001)
      suggesting the existence of an anamnestic response. We conclude that in
      immunocompetent population it is not necessary to administer a booster dose 6.5
      years after hepatitis B vaccination.

PMID- 11599690
TI  - HIV seroconverters: using surveillance to characterise people with incident HIV
      infection in Victoria, Australia.
AB  - This paper describes a cohort of people living in Victoria, Australia, diagnosed
      with incident HIV infection and identified through routine HIV surveillance. All
      HIV diagnoses notified to the Victorian HIV Registry between January 1997 and
      September 1998 were included. Infections were classified as incident if there was
      a prior negative test and/or seroconversion illness within 12 months of the first
      positive HIV test. During the study period there were 277 notifications received
      of which 70 (25%) were incident infections (seroconversions). People with
      incident infection were aged 36 years (+/- 10), from an Anglo background (76%)
      and living in Melbourne (91%). Seroconverters were more likely to have acquired
      their infection in Victoria (76%), through male-to-male sexual contact (86%), and
      from casual or anonymous partners (67%). Cohorts of individuals with incident HIV
      infection provide a valuable resource for understanding the dynamics of HIV
      acquisition and natural history of the infection.

PMID- 11599691
TI  - Effectiveness of influenza vaccination in the elderly in a community in Italy.
AB  - OBJECTIVES: Assess the effectiveness of influenza vaccination in reducing
      hospitalization due to pneumonia and influenza among elderly subjects in a
      community in central Italy. Estimate the hospitalization fraction preventable by
      extending the vaccination program. METHODS: Case-control study. Cases were
      subjects aged 65+ at hospital admission (1 December 1994-31 March 1995). For each
      case two population controls were randomly chosen, matched by sex, age and
      residence. Variables of interest were recorded through a postal questionnaire and
      telephone interview. A matched-set analysis was carried out adjusting for
      concomitant chronic diseases, education, type of home heating, and smoking
      habits. The preventable fraction of hospitalization was computed through the
      application of the attributable risk estimate. The setting was 33 municipalities
      in central Italy including 169,370 residents aged 65 years or more. RESULTS: Two
      hundred and seventy-five cases 550 controls were analyzed. Influenza vaccination
      was effective in preventing 33% of hospitalization due to pneumonia/influenza.
      The fraction of hospital admissions preventable by extending the vaccination was
      17%. When the analysis was limited to self-respondents to the questionnaire
      (excluding next-of-kin) and to pneumonia/influenza as primary discharge
      diagnosis, protection from hospitalization by vaccination almost reached 50%, a
      better result in comparison with most case-control studies. CONCLUSIONS:
      Influenza vaccination was shown to be successful in reducing hospital admissions
      due to pneumonia and influenza. A large number of hospitalizations could be
      reduced extending the vaccination campaign.

PMID- 11599692
TI  - Population-based study of cutaneous malignant melanoma in the Granada province
      (Spain), 1985-1992.
AB  - Cutaneous melanoma has received substantial attention during the last years
      because of the increase in its incidence which has been registered in many
      countries. This paper aims at describing the incidence and characteristics of all
      new cutaneous malignant melanoma cases during 1985-1992 reported to the Granada
      Cancer Registry (Spain) in the context of Mediterranean populations. A population
      based study with 247 cutaneous melanoma cases was carried out. The variables used
      were: sex, age, anatomic site, hystological type, level of invasion and tumour
      thickness. The Age-Standardised incidence Rate per World population (ASRW) was
      2.9 for males and 3.7 for females in the whole period. An increasing incidence
      trend for both males and females was found. The ASRW in 1985-1987, 1988-1990 and
      1991-1992 was respectively 2.2, 2.9 and 3.2 for males and 3, 3.4, 4.7 for
      females. The most frequent location was trunk for males (36%) and lower
      extremities for females (44%). The most frequent hystological type for both males
      and females was superficial spreading melanoma. Seventy-six percent of males and
      60% of females were diagnosed Clark's level III or over. Average tumour thickness
      was 3.3 mm for males and 2.4 mm for females. The results of this study can be a
      guidance for the setting up of health policies which would contribute to the
      prevention of the disease and to an improvement in care. Because of the increase
      in incidence rates and the high percentage of cases which were diagnosed at
      advanced stages, it is advised that prevention campaigns are addressed to the
      Granada population.

PMID- 11599693
TI  - Transmission of hepatitis A in hamburg, germany, 1998-1999--A prospective
      population based study.
AB  - To study the pattern of transmission of HAV in a large urban community a
      prospective cohort study was conducted in Hamburg between 1 January 1998 and 31
      December 1999. Four hundred and eleven patients were classified as hepatitis A
      cases comprising 144 foreign and 267 German persons. Univariate analyses were
      carried out to examine differences between socio-demographic, clinical and
      behavioural characteristics. To determine independent predictors for HAV
      infection a multiple logistic-regression model was used. The principal risk
      factor was travel to areas where hepatitis A is endemic, with 32.6% (n= 134/411)
      of all documented cases of hepatitis A. Foreign patients who had acquired the
      infection abroad, mostly children, accounted for the majority of these cases. Of
      all 411 cases, 42 (10.2%) were associated with parenteral drug, followed by day
      care or school contact (8.3%; n = 34). Outbreaks contributed to 11.4% of cases (n
      = 47), but only 7.1% (n = 29) were household contacts. The low incidence rate
      among exposed persons in the households of those infected was similar in the
      groups of foreign and German nationals (17/384 = 4.4% and 12/231 = 5.2%,
      respectively), which may demonstrate a good hygienic level in general. Our
      findings suggest that preventive measures such as the improvement of hygienic
      conditions in a defined general population may contribute to a reduced incidence
      of hepatitis A. Nevertheless, because hygienic standards may change with time,
      this policy should be supplemented by targeted vaccination of groups at risk.

PMID- 11599694
TI  - Influence of socio-economic crisis on epidemiological characteristic of suicide
      in the region of Nis (southeastern part of Serbia, Yugoslavia).
AB  - It is well known that gross social crises greatly influence the change in
      epidemiological features of suicide. The aim of this study is to determine
      whether the social-economic crisis in Yugoslavia influenced the change in
      epidemiological features of suicide in the region of Nis (southeastern Serbia).
      The material included death certificates for 1987-1999. The rates were calculated
      per 100,000 inhabitants (1991 Census) and standardization was performed by direct
      method (Segi's world population was used as standard population). Generally,
      trends for suicide rates in the region of Nis from 1987 to 1999 have decreasing
      tendency among both sexes. The average annual suicide rate in the region during
      the period 1987/1989 (relatively economically and politically stable) was 14.8
      among males, and 6.8 among females. In 1999 (maximum influence of socio
      economical and political crisis) suicide rate among males was 13.8 and among
      females it was 3.7. The decrease in suicide rate in females can be observed in
      all age groups, and in males in the age groups 15-29 and 50-64. During 1999,
      compared to 1987/1989, the increase in the number of suicides is perceived in the
      summer months (1999 -41.5%; 95% CI: 30.8-52.2%; 1987/ 1989 -23.8%; 95% CI: 18.9
      28.7%), as well as the decrease of suicide on Monday (1987/1989 -21.2%; 95% CI:
      16.2-26.1%; 1999 -9.8%; 95% CI: 3.4 16.2%). During 1999 the rate of suicides
      committed by fire arms increased (from 8.1 to 14.5%), while there was a decrease
      in poisoning, in both males (from 26.3 to 9.7%; p < 0.05) and females (from 39.1
      to 10.0%; p < 0.05). During 1999 significant changes in epidemiological features
      of suicide were registered, compared to 1987/1989. These changes were probably
      enhanced by changed socio-economic factors (primarily war action and the bombing
      of Serbia, as well as the decline of standard of living and other aspects of
      economic and political crisis), which requires additional, more complete and
      thorough research.

PMID- 11599695
TI  - Hantavirus infections in Greece--an update.
AB  - Hantaviruses are emerging viruses spread worldwide and cause hemorrhagic fever
      with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). Two pathogenic
      hantaviruses are present in Greece: Dobrava/Belgrade virus (DOBV) and Puumala
      virus (PUUV). The predominant one is DOBV, carried in Greece by the rodent
      Apodemus flavicollis. Most human infections are sporadic, but epidemic outbreaks
      were also described. The severity of the disease ranges from a mild or moderate
      form to severe and fatal cases. Several endemic foci for HFRS have been
      identified. Phylogenetic analysis of hantavirus sequences revealed a stable
      geographical distribution.

PMID- 11599696
TI  - Effect of photoperiod and quantitative feed restriction in a broiler strain on
      onset of lay in females and onset of semen production in males: a genetic
      hypothesis.
AB  - The effects of feed restriction and photoperiod on body weight (WTSXM) and age
      (ASXM) at onset of mature semen production in males and onset of lay in females
      of a broiler female line were examined. Feeding treatments were as follows: ad
      libitum (AL) and quantitative feed restriction (QR). Photoperiod treatments were
      as follows: open shed (OS), in which the chicks were reared under naturally
      increasing daylight with supplemental light; dark room (DR), in which chicks were
      reared under short days, gradually increasing from 6 h of light (L) to 11.5L; and
      dark room to open shed (DR-OS), in which chicks reared under short days in the
      dark room were transferred to the open shed at 149 d. Treatment effects were
      similar in direction in males and females, suggesting similar control of entry
      into reproduction of the two sexes, although within a given treatment, males
      matured earlier than females. Effects of feeding and photoperiod treatments were
      additive. Relative to QR, the AL feeding treatment increased WTSXM by 832 g for
      males and 1,089 g for females; ASXM was decreased by 15.8 d for males and 9.3 d
      for females. Relative to OS, the DR photoperiod increased WTSXM by 591 g for
      males and 513 g for females; ASXM was increased by 17.5 d for males and 26.8 d
      for females. The DR-OS photoperiod increased WTSXM by 86 and 169 g for males and
      females, respectively; ASXM was increased by 6.1 d and 4.9 d, respectively. Under
      DR, the delay in onset of sexual maturity caused by QR was not due to failure to
      reach threshold body weight or age and, hence, appears to have resulted from the
      feed restriction itself. A similar delay for QR was found under OS but might have
      been due to failure to reach threshold body weight. It is speculated that the
      delay in onset of sexual maturity caused by feed restriction may be an ecological
      adaptation or, alternatively, a result of nutritional imbalance.

PMID- 11599697
TI  - Prestorage incubation of long-term stored broiler breeder eggs: 1. Effects on
      hatchability.
AB  - Two thousand eight hundred broiler breeder eggs were used to determine if
      prestorage incubation (PRESI) treatments of 0, 6, 12, or 18 h (at 37.5 C) could
      improve the hatchability of eggs stored (at 11.5 C) for 4 vs. 14 d. Embryonic
      development of 30 eggs was established after exposing the eggs to each PRESI
      treatment. The remaining eggs were cold-stored for 4 or 14 d and then incubated
      for 21 d. Unhatched eggs were broken open to determine fertility, and if fertile,
      stage of embryonic death was determined. Statistical significance was assessed at
      P < 0.05. Embryonic development significantly advanced (P = 0.00001) as the
      number of PRESI h increased. Therefore, embryos from each of the four PRESI
      treatments were placed into cold storage at different stages of development. Egg
      storage for 14 vs. 4 d significantly reduced the hatchability of all eggs set
      (58.4 and 88.2%, respectively). The PRESI treatments did not have a significant
      beneficial or detrimental effect on the hatchability of all eggs set for the eggs
      stored 4 d. However, in eggs stored for 14 d, PRESI for 6 h significantly
      improved hatchability of all eggs set (79.0%) when compared to eggs that were not
      PRESI (70.5%). The hatchability of all eggs set for eggs PRESI for 18 h and
      stored for 14 d was significantly reduced (9.1%) when compared to the other 14-d
      stored PRESI treatments. The results of this study provide evidence that embryos
      of eggs that have completed hypoblast formation (PRESI for 6 h) and are stored
      for 14 d have a survival advantage over embryos of 14-d stored eggs that have not
      been subjected to any PRESI treatments.

PMID- 11599698
TI  - Sporulation of Eimeria maxima oocysts in litter with different moisture contents.
AB  - The aim of this study was to determine if the sporulation of Eimeria maxima
      oocysts was affected by the moisture content of the litter. Fresh feces were
      collected from chickens experimentally infected with E. maxima. The feces were
      mixed with dried wood shavings and different amounts of water to obtain final
      moisture contents of 16, 42, and 62% and a final oocyst concentration of 5,000
      per g of mixture. The samples were kept at 23 C and 75% relative humidity and
      were thoroughly aerated every 12 h. Oocysts kept under ordinary laboratory
      sporulation conditions in 2% wt/vol aqueous potassium dichromate at 27 C were
      used as a standard for optimal sporulation. The proportion of sporulated oocysts
      was determined microscopically every 12 h. Sporulation of E. maxima was most
      efficient under the driest conditions studied (16% moisture content), and poorest
      in the samples with the highest moisture content (62%). Even though the
      differences may not have resulted from a direct effect of humidity on the
      oocysts, but more likely resulted from limited oxygen in the moister substrates,
      it is clear that sporulation is not favored by moist litter.

PMID- 11599699
TI  - Humoral and cellular immune responses in turkey poults infected with turkey
      coronavirus.
AB  - The objective of the present study was to elucidate the kinetics of humoral and
      cellular immune responses of turkey poults infected with turkey coronavirus
      (TCV). Turkey poults were orally inoculated with TCV at 10 d of age, and the
      immune responses were analyzed at 1, 3, 7, 14, 21, 28, 42, and 63 d postinfection
      (PI) in three different experiments. Total Ig to TCV was initially detected at 7
      and 14 d PI in Experiments 1 and 3. In addition, Ig gradually increased from 7 to
      21 d PI and remained at 80 immunofluroescent antibody assay (IFA) titers or more
      thereafter. Lymphocyte proliferation responses of spleen cells to concanavalin A
      were higher in TCV-infected turkeys than in noninfected control turkeys with
      significant differences (P < 0.05) being noted at 14 and 63 d PI in Experiment 2
      and at 3 and 28 d PI in Experiment 3. Strong IFA staining response to TCV antigen
      was observed in intestines of turkeys at 1, 3, and 7 d PI, and the response
      declined from 14 to 28 d PI in Experiment 3. In Experiment 3, the IgG isotype
      antibody response to TCV was markedly increased after 21 d PI and remained high
      until 63 d PI. The IgM isotype antibody response to TCV was 1.40 and 0.91 at 7
      and 14 d PI, respectively. The IgA isotype antibody response to TCV was very low
      as detected at 7 (0.13), 14 (0.20), and 21 (0.17) d PI. Turkeys infected with TCV
      had significantly higher (P < 0.05) antibody response to sheep erythrocytes than
      noninfected controls at 7 d PI. Virus-specific lymphocyte proliferation response
      of spleen cells was significantly stimulated (P < 0.05) at 63 d PI in Experiment
      3. The proportion of the CD4+ subpopulation of T lymphocytes was significantly
      increased (P < 0.05) at 1, 7, and 21 d PI in Experiment 3. The results indicate
      that humoral and cellular immunities to TCV are elicited in turkeys following
      infection with TCV.

PMID- 11599700
TI  - Optimum site for in ovo amino acid injection in broiler breeder eggs.
AB  - Three experiments were conducted to evaluate the effect of differences in in ovo
      amino acid (AA) injection sites in broiler breeder eggs on subsequent
      hatchability and BW of chicks. In Experiment 1, an AA solution was injected into
      eggs with 13-mm or 19-mm, 27-ga needles. Uninjected eggs served as controls.
      Hatchability was decreased (P < 0.05) in eggs receiving AA injections with the 19
      mm needle in comparison to the control and 13-mm-injected groups. However, BW of
      chicks increased (P < 0.05) relative to pre-incubational egg weight by AA
      injection with the 13-mm needle. In order to evaluate the in ovo location of AA
      injections from Experiment 1, India ink was injected into eggs in Experiment 2
      with a 13-or 19-mm needle. Immediately after injection, the air cell end of the
      egg was windowed in order to observe effects of injection site. Windowing of eggs
      was accomplished by removing a piece of the eggshell over the air cell and the
      underlying membrane at Day 7 of incubation. The amount of injected India ink was
      higher in the extra-embryonic coelom in eggs treated by both needles. However,
      the occurrence of India ink in the extra embryonic coelom was higher (P < 0.05)
      in the group injected with AA solution using a 13-mm needle as compared to that
      after injection using a 19-mm needle. The observation of India ink in the
      amniotic cavity was higher (P < 0.05) in the group injected with AA solution
      using a 19-mm needle rather than that using a 13-mm needle. In Experiment 3,
      treatments consisted of control (uninjected eggs) or windowed eggs. Windowed eggs
      received AA to the chorioallantoic membrane, the yolk, extra-embryonic coelom, or
      amniotic cavity at Day 7 of incubation. Hatchability was reduced, but chicks
      hatched when eggs were windowed and when AA were injected into the yolk sac or
      extra-embryonic coelom. However, chicks did not hatch when AA were administered
      to the chorioallantoic membrane or into the amniotic cavity. These results
      suggest that the best AA injection sites in ovo may be the yolk and extra
      embryonic coelom.

PMID- 11599701
TI  - Embryo growth and amino acid concentration profiles of broiler breeder eggs,
      embryos, and chicks after in ovo administration of amino acids.
AB  - Two experiments were conducted to evaluate the effect of in ovo amino acid (AA)
      injections in broiler breeder eggs on AA utilization of embryos. All AA used in
      these experiments were pure crystalline AA in free-base form. Treatments in
      Experiment 1 comprised 1) control eggs (no injection), 2) 0.5 mL sterile
      distilled water injected eggs, and 3) eggs injected with an AA solution suspended
      in 0.5 mL sterile-distilled water. Injections were administered into the yolk at
      Day 7 of incubation. At hatch, chicks were killed and bled, and plasma AA
      concentration was determined. Plasma AA concentration of hatched chicks decreased
      (P < 0.05) when water was injected. In addition, all AA from eggs injected with
      AA, except Glu and Lys, were decreased (P < 0.05) at hatch as compared to control
      eggs. However, AA pattern was not affected by in ovo water injection, but the AA
      ratio to Lys was reduced by in ovo AA injection. Experiment 2 was conducted to
      evaluate whole internal egg AA concentrations over incubation time in the
      presence or absence of in ovo AA administration. Treatments in Experiment 2
      comprised 1) control eggs (no injection), and 2) eggs injected with a AA solution
      at Day 7 of incubation. The AA contents of embryo, yolk, albumen, and allantoic
      and amnion fluids were analyzed over time during incubation (Days 0, 7, 14, and
      19 of incubation). On Day 14 of incubation, there were no differences in AA
      contents of all tissues between the control group and the group injected with AA
      on Day 7 of incubation. On Day 19 of incubation, AA contents of embryo, yolk,
      albumen, and allantoic and amnion fluids were increased (P < 0.05) as mediated by
      in ovo administration of AA at Day 7 of incubation. These results suggest that in
      ovo administration of AA may increase AA concentrations in chicken embryos and
      other egg contents.

PMID- 11599702
TI  - Near- versus mid-infrared diffuse reflectance spectroscopy for determination of
      minerals in dried poultry manure.
AB  - The objective of this study was to determine if accurate calibrations for mineral
      content in dried poultry manures could be developed using near- or mid-infrared
      spectra. Samples (n = 124) were obtained from a commercial testing laboratory
      along with conventionally determined values for Ca, Cu, K, Mg, Mn, P, S, and Zn.
      Samples were blended in a food blender, dried at 60 C, ground to 20 mesh, and
      scanned in the near-infrared (rotating sample cup) on a scanning monochromator.
      Samples were also scanned in the mid-infrared on a Fourier transform spectrometer
      using a custom-made sample transport. Results showed that calibrations based on
      nearor mid-infrared spectra were not satisfactory for the accurate determination
      of Ca, Cu, K, Mg, Mn, P, S, or Zn in dried poultry manures. At best, most of the
      calibrations would be suitable for only gross estimates, although the mid
      infrared calibration for P might be suitable for some needs in which only a
      limited degree of accuracy was needed. Either spectral range could be used to
      separate dried poultry manure samples into those containing less than 3% and
      greater than 8% Ca but not to accurately differentiate samples within those two
      groupings. Finally, although the mid-infrared calibrations were the more accurate
      for five of the eight minerals studied, the differences between the two sets of
      calibrations were so varied that it would be difficult to say that one region is
      better for mineral content measurement.

PMID- 11599703
TI  - Effects of incubator humidity and hen age on yolk composition in broiler hatching
      eggs from young breeders.
AB  - The effects of broiler breeder age (26, 28, and 30 wk) and incubator relative
      humidity (43, 53, and 63% RH) on yolk sac weight and composition in broiler
      hatching eggs between 16 and 19 d of incubation were evaluated. Percentage yolk
      sac weight was reduced in eggs from the youngest (26 wk) breeder hens and in eggs
      incubated at 53% RH. Percentage yolk moisture, in eggs from the youngest hens,
      was lowest at 16 d and was highest at 19 d, and percentage yolk lipid was highest
      at 16 and 17 d of incubation in eggs from 30-wk-old hens. Percentage yolk lipid
      content was higher at 63% RH compared with 53% RH in eggs from 26-wk-old breeders
      but was lower in eggs incubated at a 43% RH compared with 53 and 63% RH from 30
      wk-old breeders. Yolk stearic and arachidonic acid concentrations were higher and
      myristic acid concentration was lower in eggs from the 26-wk-old hens.
      Conversely, the highest yolk concentrations of linolenic and palmitoleic acids
      occurred in eggs from 30- and 28-wk-old breeders, respectively. At 16, 17, 18,
      and 19 d of incubation, yolk oleic acid concentrations were significantly, but
      variably, affected by breeder age, whereas linoleic acid concentration was
      highest in 26-wk-old breeders only at 19 d. Palmitic acid concentration at 17 d
      was lower in eggs incubated at 53% RH compared with 43 and 63% RH. Rate of yolk
      uptake from the yolk sac by embryos may be increased by incubating eggs at 53%
      RH, and the effects of changes in RH between 43 and 63% on yolk lipid content are
      influenced by breeder age.

PMID- 11599704
TI  - Efficacy of in-feed tylosin phosphate for the treatment of necrotic enteritis in
      broiler chickens.
AB  - The efficacy of tylosin phosphate for the treatment of necrotic enteritis (NE)
      was investigated in a floor pen study of 2,000 broiler chickens. A model in which
      Clostridium perfringens was administered in the feed on Days 14 to 16 was used to
      initiate an outbreak of NE. Treatments, allocated at the pen level in a
      randomized complete block design, consisted of five levels of tylosin phosphate
      (0, 50, 100, 200, or 300 ppm) administered in the feed on Days 15 to 22,
      following the identification of an outbreak of NE on Day 15. Mortality due to NE
      was significantly reduced (P < 0.05) for medicated birds at all dose levels of
      tylosin phosphate compared to unmedicated birds. Mean NE lesion scores on Day 17
      were significantly reduced (P < 0.05) by all levels of tylosin treatment compared
      to those of unmedicated birds, decreasing linearly from 2.66 at 0 ppm to 0.38 at
      100 ppm and 0 at higher doses. Tylosin at all levels provided improvement in Day
      29 body weight, average daily gain, feed to gain ratio, and average daily feed
      intake compared to unmedicated birds. The results of this study provide evidence
      that tylosin phosphate, when administered in feed, is effective in the treatment
      of clinical outbreaks of NE in broiler chickens and suggest that the optimal dose
      for this purpose is 100 ppm.

PMID- 11599705
TI  - Behavior of the domestic fowl in the presence of vertical panels.
AB  - The effects of environmental complexity on the time budget of chickens were
      investigated. It was hypothesized that the provision of vertical panels to pen
      centers would generate additional protective areas within the pen, influencing
      the amount of time spent performing different behaviors. The experiment consisted
      of three cover treatments (mesh panels, frame panels, and no cover) and two group
      sizes (80 and 110). Vertical panels, constructed of polyvinyl chloride piping,
      were positioned in pen centers, whereas pen centers in the no-cover treatment
      were left empty. Drinking, dust bathing, feeding, foraging, movement, preening,
      resting, and standing were recorded during continuous focal sampling of 210 focal
      individuals from 5 to 44 d of age. Resting was the most frequent behavior
      accounting for over 64% of the chicken time budget. Resting time was influenced
      by the presence of cover (P < 0.01), and was higher in pens enriched with panels.
      Time spent moving and standing in the different pen regions was influenced by the
      presence of cover (P < 0.01) and age (P < 0.05). The presence of cover did not
      influence time spent feeding or drinking, but both behaviors were affected by age
      (P < 0.05). The presence of cover influenced time spent foraging, which occurred
      more often in the pens containing no panels (P = 0.05). Preening and dust bathing
      were the only behaviors influenced by group size (P < 0.05). These results
      suggest that incorporating enrichment into the environment does influence the
      time a chicken will spend performing different behaviors.

PMID- 11599706
TI  - Effect of supplementation of two different sources of phytase on egg production
      parameters in laying hens and nutrient digestiblity.
AB  - Hens were fed corn-soybean meal diets containing 0.35, 0.25, 0.15, or 0.10%
      nonphytate phosphorus (NPP) (40 to 60 wk). Phytases A and B were added at 0.25,
      0.15, and 0.10% at 250 to 300 units of phytase (FTU)/kg feed in a 3 x 3
      factorial; 0.35% was a control diet. Treatments were replicated with eight cages
      per treatment (five hens per cage) in a randomized complete block design. Phytase
      supplementation had a significant effect on several production parameters: feed
      intake, feed conversion, and egg mass. Results showed nonsignificant effects (P <
      0.06) on feed intake when hens were supplemented with phytase A or B and consumed
      more feed compared to the basal diet at 0.10% NPP. The feed conversion of birds
      fed 0.10% NPP without phytase was the least efficient compared to the other nine
      treatments (P < 0.05). Egg mass was significantly greater for hens supplemented
      with phytases A and B than for hens fed the basal diet at low (0.10%) NPP (P <
      0.05). There were no significant differences in egg production, egg weight,
      specific gravity, Haugh units, wet shell, or dry yolk percentages. Dry shell
      percentage was higher among basal diets at 0.15 and 0.25% NPP in contrast to
      phytase, whereas albumen and dry yolk percentages were significantly higher for
      diets with phytase than for the basal diet at 0.10% NPP. Bone ash percentage was
      uncharacteristically high in hens fed 0.10% NPP without phytase; however,
      mortality was 22% in this group. Phytase supplementation improved Ca and P
      digestibilities to varying degrees. Supplementation of phytase in normal, corn
      soybean meal diets improved feed intake, feed conversion, and egg mass and
      elicited a response in shell quality and egg components at the low (0.10%) NPP.

PMID- 11599708
TI  - Long-term effects of feeding flaxseed-based diets. 1. Egg production parameters,
      components, and eggshell quality in two strains of laying hens.
AB  - We used a split-plot design of five diets: control (corn-soy) with 3.8% Ca, 10%
      flaxseed with 3.8% Ca, 10% flaxseed with 4.5% Ca, 10% flaxseed with 3.8% Ca and
      22,000 IU vitamin D3/kg, and 10% flaxseed with 4.5% Ca and 22,000 IU vitamin
      D3/kg, and two strains of birds, DeKalb Delta (DD) and Hy-Line W-36 (HL), to
      evaluate long-term effects of flaxseed supplementation on egg production
      parameters. Each of the five treatments was randomly assigned and replicated six
      times with five hens per replicate pen from 21 to 57 wk of age. Phase I was from
      21 to 39 wk, Phase II was from 40 to 48 wk, and Phase III was from 49 to 57 wk.
      Feed consumption was significantly (P < 0.04) greater for the hens fed 10%
      flaxseed diets (100.9 g) when compared to the corn-soy controls (99.3 g). Overall
      average egg production (P < 0.05) was 87.8, 87.1, 86.0, 87.1, 84.8, for diets 1,
      2, 3, 4, and 5, respectively. Average hen weights during the study were
      significantly lower for the flaxseed-fed hens (1.559 kg) compared to the controls
      (1.616 kg). Egg weight was significantly affected by diet during Phase III with
      heavier eggs from flaxseed fed hens (62.6 g) compared to controls (61.44 g), but
      overall egg weight was not significantly affected. Average egg mass was not
      significantly affected by dietary treatments, but DD hens had a decrease in egg
      mass with Ca supplementation (Diet 2 vs. Diet 3), whereas HL egg mass increased
      with Ca supplementation. Percentage albumen had a significant strain effect and
      strain by diet interactions. Overall, significantly less albumen (P < 0.001) was
      produced by HL (59.4%) compared to DD (61.3%). Supplemental Ca increased albumen
      percentage in DD (interaction effect P < 0.03) and decreased albumen percentage
      in the HL strain. Flaxseed supplementation significantly increased albumen
      percentage (P < 0.02) when compared to the corn-soy control, 60.5 and 59.9%,
      respectively. An interaction effect (P < 0.01) was noted for percentage wet yolk,
      in which increasing Ca decreased wet yolk percentage in DD but increased yolk
      percentage in HL. Wet yolk percentage was also significantly (P < 0.001) less in
      DD (25.0%) when compared to HL (26.9%). Addition of flaxseed decreased yolk
      percent when compared to controls (P < 0.03) during Phase II. Ca supplementation
      significantly (P < 0.03) increased yolk solids in both strains. Grams of yolk
      solids per egg were affected by flaxseed supplementation (P < 0.06). Flaxseed
      eggs contained 7.18 g per egg yolk solids compared to 7.3 g in corn-soy control
      group. Wet shell percentage was significantly lower in the flaxseed diets (12.4%)
      when compared to the controls (12.6%). Addition of flaxseed to the diet of laying
      hens did not have any adverse effects on egg production parameters, but flaxseed
      supplementation can significantly alter weight of yolk solids and yolk and
      albumen percentages.

PMID- 11599707
TI  - Relationship of dietary lysine level to the concentration of all essential amino
      acids in broiler diets.
AB  - A study was conducted to evaluate the relationship of dietary Lys and other
      essential amino acids (EAA) in diets for broilers. Diets were formulated based
      upon NRC (1994) recommendations. Within each age period, diets contained NRC
      recommended levels of Lys with other EAA at 100, 110, 120, or 130% of NRC. The
      diets were then supplemented with 0.1, 0.2, or 0.3% additional Lys, resulting in
      a 4 x 4 factorial arrangement with four levels of Lys (NRC, + 0.1%, + 0.2%, and +
      0.3% Lys) and four levels of other EAA (100, 110, 120, and 130% of NRC). Each of
      the 16 treatments was fed to six replicate pens of 25 male broilers of a
      commercial strain. At 56 d, five birds per pen were processed to determine
      dressing percentage and carcass yield. There were no significant interactions
      between level of Lys and levels of other EAA for live performance or carcass
      characteristics. The BW was significantly increased at 21 and 42 d by addition of
      + 0.1% Lys above NRC but not at 56 d. There was no significant effect of other
      EAA on BW at any age. The effects of Lys on feed conversion were varied. At 21
      and 42 d, addition of 0.1% Lys to diets containing the NRC Lys level
      significantly improved feed conversion; response to 0.2 or 0.3% Lys were varied.
      No significant effects of Lys on feed conversion were observed at 56 d.
      Increasing the level of EAA resulted in significant improvements in feed
      conversion at 21, 42, and 56 d, generally following a linear trend. Dietary Lys
      levels had no significant effects on dressing percentage, breast meat yield, or
      abdominal fat content. The level of other EAA significantly influenced dressed
      yield but had no significant influence on carcass yield. These results indicate
      that NRC (1994) levels of Lys and other EAA are adequate for optimum performance
      of male broilers processed at 56 d but may be less than adequate at younger ages.

PMID- 11599709
TI  - Yolk and exogenous feed utilization in the posthatch chick.
AB  - This study examined in posthatch chicks the partition of yolk utilization between
      transport to the circulation and secretion to the intestine and determined
      absorption and plasma concentrations of some metabolites. The presence of feed in
      the gastrointestinal tract enhanced yolk secretion to the small intestines.
      Absorption of glucose, methionine, and oleic acid was determined in vivo close to
      hatch using 141Ce as a nonabsorbed reference substance. Glucose and methionine
      uptake was low posthatch and increased with age and feed intake. Oleic acid
      uptake was high at hatch and changed little with age. Increased intake of lipids
      depressed the percentage oleic acid absorption. Plasma concentrations of glucose,
      Na, phospholipids, and nonesterified fatty acids did not change with age.
      Triiodothyronine and triglyceride concentrations increased with age in the plasma
      of fed chicks but decreased during feed deprivation. Feed intake stimulated
      posthatch secretion of yolk to the small intestines and triggered uptake
      mechanisms for hydrophilic compounds.

PMID- 11599710
TI  - Alpha-tocopherol transfer efficiency and lipid oxidation in fresh and spray-dried
      eggs enriched with omega3-polyunsaturated fatty acids.
AB  - We evaluated the effect of supplementing a basal diet containing 5% linseed oil
      with 0, 50, 100, and 200 mg/kg of alpha-tocopheryl acetate (alpha-TA) on alpha
      tocopherol content, fatty acid composition, and lipid oxidation in fresh and
      spray-dried eggs during storage. Alpha-tocopherol transfer efficiency from feed
      to egg was also studied. The alpha-tocopherol content of fresh egg increased in a
      dose-dependent manner (16.6, 49.8, 78.9, and 132.3 microg/g of egg for 0, 50,
      100, and 200 mg/kg alpha-TA supplementation, respectively), but transfer
      efficiency decreased, from 41.8% to 26.7%, with increasing alpha-tocopherol
      content in the diet. Spray-drying significantly decreased the alpha-tocopherol
      content of eggs and increased lipid oxidation. Dietary supplementation with
      different levels of alpha-TA significantly reduced lipid oxidation in spray-dried
      eggs. Alpha-TA supplementation had no significant effect on the fatty acid
      composition of fresh eggs.

PMID- 11599711
TI  - Unhydrolyzed vegetable sucrose polyester in broiler diets.
AB  - Duplicate 42-d broiler studies were conducted in pens with litter on the floor,
      beginning with 1-d-old chicks obtained from a commercial hatchery. Seven
      replicate pens, each starting with 12 male and 12 female chicks, received each
      dietary treatment in a randomized-block design. Dietary treatments comprised 0,
      0.5, 1.0, 1.5, 2.0, or 2.5% unhydrolyzed vegetable sucrose polyester (UVSP) added
      to the starting and finishing diets at the expense of filler. In both studies, up
      to 2.5% UVSP did not have a significant negative effect on body weights, daily
      feed intake, feed conversion, or litter moisture. In Experiment 2, average body
      weights were significantly greater than control for groups that received 0.5,
      2.0, or 2.5% UVSP. However, the degree of shank yellowness as measured with a
      Minolta Chroma-meter was consistently and significantly reduced by 0.5% or more
      UVSP. Although xanthophyll levels were intentionally lowered somewhat to improve
      sensitivity (7.9 and 9.6 mg/kg for starter and finished feeds, respectively), it
      is obvious that the utilization of xanthophyll was reduced somewhat by UVSP.
      Additional pigment titration trials could provide valuable information about the
      levels required to overcome this effect.

PMID- 11599713
TI  - Marination performance of pale broiler breast meat.
AB  - Pale, soft, exudative (PSE) meat is a growing problem in the poultry industry and
      is characterized by rapid postmortem pH decline. The low pH condition while the
      body temperature has not yet chilled leads to protein denaturation, causing pale
      color and reduced water-holding properties. The water loss and the protein damage
      from the PSE condition may impact the ability of the muscle to uptake or retain
      marinade solution. This study was conducted to determine if a marination with
      salt and alkaline phosphates could rectify the protein functionality losses
      imparted by the PSE condition and to determine if marinade pH affects pale and
      normal fillets in the same manner. Pale (n = 175) and normal-colored (n = 160)
      fillets were collected from deboning lines at two commercial processing plants
      based on subjective color evaluation alone. The fillets were then characterized
      by L* value, pH, and expressible moisture. They were then tumbled with a solution
      containing salt and sodium tripolyphosphate at 4 C for 30 min. Marinade uptake,
      drip loss, and cook loss were all measured. As expected, the pale fillets had
      higher L* values and lower pH values than the normal fillets. For the pH 9
      marinade, uptake and drip losses were similar in pale and normal fillets, but
      cook loss from pale fillets was greater than that of the normal fillets. Marinade
      solution at pH 11 showed no difference in pH or cook loss between pale and normal
      fillets. These results indicate that the PSE condition cannot be reversed by the
      marination treatments used in this study.

PMID- 11599712
TI  - Concentration change patterns of luteinizing hormone and progesterone and
      distribution of hierarchical follicles in normal and arrested laying turkey hens.
AB  - Young photosensitive turkey hens of a line selected for increased egg production
      (Egg line) were photostimulated with constant light [24 h light:0 h darkness] at
      30 wk of age. Egg laying became arrested in 6 of 12 the hens after only 2 to 3 wk
      of laying. Ovarian morphology and changes in concentrations of plasma hormones
      [luteinizing hormone (LH), progesterone (P4), and estradiol-17beta (E2)] over 10
      d of serial bleeding were compared between the arrested laying and normal laying
      hens. The number of ovarian follicles heavier than 1.0 g was much greater in
      arrested laying hens, and some of the arrested laying hens presented a polycystic
      ovarian follicle condition. The oviducts of the arrested laying hens were fully
      developed and were similar in weight to those of normal laying hens. In arrested
      laying hens the plasma concentration of LH was relatively low (1.72 +/- 0.30 ng
      mL(-1)) and without preovulatory surges. In normal laying hens the baseline
      concentration of LH was 2.60 +/- 0.71 ng mL(-1), and the interval between LH
      surges was 26.8 h. In the arrested laying hens, the plasma concentration of P4
      was relatively high (4.66 +/- 1.28 ng mL(-1)) and without preovulatory surges. In
      normal laying hens the baseline concentration of P4 between surges was 1.76 +/-
      0.24 ng mL(-1). Plasma E2 concentrations were not different between normal laying
      and arrested laying hens. In conclusion, ovulations and ovipositions ceased in
      the arrested laying hens, but the entrance of follicles into the follicular
      hierarchy and hierarchical growth continued, leading to an accumulation of
      numerous mature follicles in the ovary. In addition, some of the accumulated
      mature follicles might have resumed growing, leading to the formation of cystic
      ovarian follicles.

PMID- 11599714
TI  - Microbial metabolism as an evolutionary response: the cybernetic approach to
      modeling.
AB  - The growth and metabolic capabilities of microorganisms depend on their
      interactions with the culture medium. Many media contain two or more key
      substrates, and an organism may have different preferences for the components.
      Microorganisms adjust their preferences according to the prevailing conditions so
      as to favor their own survival. Cybernetic modeling describes this evolutionary
      strategy by defining a goal that an organism tries to attain optimally at all
      times. The goal is often, but not always, maximization of growth, and it may
      require the cells to manipulate their metabolic processes in response to changing
      environmental conditions. The cybernetic approach overcomes some of the
      limitations of metabolic control analysis (MCA), but it does not substitute MCA.
      Here we review the development of the cybernetic modeling of microbial
      metabolism, how it may be combined with MCA, and what improvements are needed to
      make it a viable technique for industrial fermentation processes.

PMID- 11599715
TI  - Transformation systems of non-Saccharomyces yeasts.
AB  - This review describes the transformation systems including vectors, replicons,
      genetic markers, transformation methods, vector stability, and copy numbers of 13
      genera and 31 species of non-Saccharomyces yeasts. Schizosaccharomyces pombe was
      the first non-Saccharomyces yeast studied for transformation and genetics. The
      replicons of non-Saccharomyces yeast vectors are from native plasmids,
      chromosomal DNA, and mitochondrial DNA of Saccharomyces cerevisiae, non
      Saccharomyces yeasts, protozoan, plant, and animal. Vectors such as YAC, YCp,
      YEp, YIp, and YRp were developed for non-Saccharomyces yeasts. Forty-two types of
      genes from bacteria, yeasts, fungi, and plant were used as genetic markers that
      could be classified into biosynthetic, dominant, and colored groups to construct
      non-Saccharomyces yeasts vectors. The LEU2 gene and G418 resistance gene are the
      two most popular markers used in the yeast transformation. All known
      transformation methods such as spheroplast-mediating method, alkaline ion
      treatment method, electroporation, trans-kingdom conjugation, and biolistics have
      been developed successfully for non-Saccharomyces yeasts, among which the first
      three are most widely used. The highest copy number detected from non
      Saccharomyces yeasts is 60 copies in Kluyveromyces lactis. No general rule is
      known to illustrate the transformation efficiency, vector stability, and copy
      number, although factors such as vector composition, host strain, transformation
      method, and selective pressure might influence them.

PMID- 11599716
TI  - Determination of DDT and its metabolites in cattle dip soil available in aqueous
      phase after remediation.
AB  - Soil taken from a former cattle tick dip site in NSW Australia, was remediated
      with a chemical leaching technology. The pre- and post-remediated soil (20g) was
      dispersed in water (100mL) and subjected to passive diffusion using polymeric
      membranes. The remediation reduced tDDT from 1174.3 microg/g to 102.9 microg/g
      (ash weight basis), which was further reduced to 43.2 microg/g with composting.
      The membranes accumulated 41.3 microg tDDT/g from the dip soil, 49.2 microg
      tDDT/g from the chemically leached soil and 3.1 microg tDDT/g from the leached
      composted soil. The chemical leaching removed over 90% of the tDDT, but released
      soil bound DDT, which was converted to DDE, while 2.99 microg/g was accumulated
      by the membranes from dip soil, 37.52 microg/g was accumulated from remediated
      soil. Composting, however, almost eliminated the availability for passive
      diffusion by the membranes from 50-60 microg/g in remediated soil to 3 -3.5
      microg/g in composted soil. Variability studies of the membranes using eight
      replicates demonstrated that the accumulation by the membranes was reproducible
      with an average relative error of 20.3% for p,p'-DDT in soil type two, whilst the
      lowest average relative error for p,p'-DDE was 4.3%, suggesting that triplicate
      analyses will achieve acceptable accuracy.

PMID- 11599717
TI  - Comparison between solid-phase extraction methods for the chromatographic
      determination of organophosphorus pesticides in water.
AB  - A solid-phase microextraction (SPME) procedure has been developed to extract
      eight organophosphorus pesticides (OPs) in water and the method was compared with
      a conventional solid phase extraction (SPE) technique. The extracted OPs were
      analyzed by gas chromatography using thermionic specific detection. Both
      extraction methods presented linear calibration at least over the concentration
      range investigated (100 to 1000 ng x mL(-1) for SPE and 1 to 100 ng x mL(-1) for
      SPME). SPME method presented higher sensitivity than SPE. The quantitation limits
      were between 0.1 to 1.0 ng x mL(-1) for SPME depending upon the analyte, and 100
      ng x mL(-1) for SPE. The precision, as measured by the standard deviations (RSD),
      were in the range 3.6% to 5.8% for SPME and 2.4% to 9.2% for SPE. Along with the
      feature of being a solvent - free sampling technique, SPME offers additional
      benefits due to its high sensitivity, simplicity, and small size sample required
      (typically: SPE - 500 mL, SPME - 5 mL).

PMID- 11599718
TI  - Sorption and mobility of dithiopyr in golf course greens rooting medium.
AB  - Sorption and mobility of dithiopyr in golf course greens rooting medium (RM) were
      studied. The sorption increased from 20 to 27 degrees C at 24 h after treatment
      (HAT) and reached equilibrium in 48 HAT at 20 degrees C. The sorption isotherms
      had Freundlich values (KF) of 1122, 27.44 to 35.16, and 0.053 to 0.168 for peat
      moss, the RM, and quartz sand, respectively, and solid to aqueous phase partition
      coefficients (Kd) of 470 to 1706 L/kg, 14.61 to 84.4 L/kg, and 0.07 to 0.29 L/kg
      for peat moss, RM, and quartz sand, respectively. Generally, higher dithiopyr
      concentration in the aqueous solution and the reduced pH of the solution
      corresponded to the higher Kd values. The average values for dispersion (D,
      cm2/min), retardation coefficient (R), beta, and omega parameters for solute
      transport in the RM lysimeter; obtained from CXTFIT curve fitting of Br-
      breakthrough curves; were 0.95, 1.01, 1, and 93.89, respectively. After
      elutriation by 18 L of aqueous KNO3 (10 mM), greater than 90% of the added
      dithiopyr remained in the top 10 cm of the RM lysimeter and no detectable
      dithiopyr was present at depths beyond 35 cm. The lysimeter effluent contained
      dithiopyr at concentrations less than 3.5 microg/L. The R value obtained from
      CXFIT curve fitting is 38.5. Results from both sorption and mobility experiments
      indicated that dithiopyr is quite immobile in golf course greens RM and has
      minimal potential for movement into surface water drainage or ground water.

PMID- 11599719
TI  - Sorption of fipronil and its metabolites on soils from South Australia.
AB  - This paper reports on the sorption of fipronil [(+/-)-5-amino-1-(2,6-dichloro
      alpha,alpha,alpha-trifluoro-p-tolyl)-4-trifluoromethyl-sulfinylpyrazole-3
      carbonitrile] and its two main metabolites, desulfynil and sulfide derivatives on
      a range of soils from South Australia. The Freundlich sorption coefficient (Kf)
      values for fipronil on the soils ranged from 1.94 to 4.84 using a 5%
      acetonitrile/water mixture as the soil solution. Its two metabolites had a higher
      sorption affinity for soils, with Kf values ranging from 11.09 to 23.49 for the
      sulfide derivative and from 4.70 to 11.77 for the desulfynil derivative. Their
      sorption coefficients were found to be better related to the soil organic carbon
      than clay content. The presence of cosolvents in soil solutions had a significant
      influence on the sorption of fipronil. The Freundlich sorption coefficients
      showed a log linear relationship with the fractions of both acetonitrile and
      methanol in solutions. The sorption coefficient of fipronil on Turretfield soil
      in the aqueous solution was estimated to be from 13.80 to 19.19. Methanol had
      less effect on the sorption of fipronil than acetonitrile. The Kd values for
      fipronil on the eight soils using a 5% methanol/water mixture were from 5.34 to
      13.85, which reflect more closely the sorption in the aqueous solution. The
      average Koc value for fipronil on the eight South Australian soils was calculated
      to be 825+/-214.

PMID- 11599720
TI  - Transformation of the insecticide teflubenzuron by microorganisms.
AB  - Transformation of teflubenzuron, the active component in the insecticide
      commercialized as Nomolt, by soil microorganisms was studied. It was shown that
      microorganisms, belonging to Bacillus, Alcaligenes, Pseudomonas and Acinetobacter
      genera are capable to perform the hydrolytic cleavage of the phenylurea bridge of
      teflubenzuron in different positions, especially active was Bacillus brevis 625.
      The structure of the intermediates formed was established using TLC, HPLC, mass
      spectrometry and 19F NMR techniques. It was shown that for a dose range of 53-132
      microM and upon 12 days of fermentation about 30% of the teflubenzuron was
      modified. About 10-15% was transformed into 2,6-difluorobenzamide, 3-5% into 2,6
      difluorobenzoic acid, 10-12% into 2,4-difluoro-3,5-dichloro-aniline. The late
      compound gave rise to formation of a condensed compound, identified as 1,2
      bis(2,4-difluoro-3,5-dichlorophenyl)urea with molecular mass of 420. The results
      obtained indicate degradation of teflubenzuron by soil microorganisms to be a
      process to be mediated by microbial consortia, and starting with hydrolysis of
      the phenylurea bridge by several bacterial species. Subsequent further
      degradation of the aromatic degradation products has to be mediated by other
      strains known to be capable of degradation of halogenated aromatics.

PMID- 11599721
TI  - Effects of trifluralin on soil microbial populations and the nitrogen fixation
      activities.
AB  - Effects of trifluralin on soil microbial populations and the nitrogen fixation
      activity of nitrogen-fixing bacteria Azotobacter chroococcum and Bradyrhizobium
      japonicum and the decomposition of trifluralin by soil microorganisms were
      studied. Trifluralin at lower concentrations from 0.5 mg microg(-1) dry soil to
      lower than 10.0 mg microg(-1) dry soil appeared to stimulate the growth of soil
      bacteria, actinomycetes, mould, and the pure cultures of Br. japonicum and A.
      chroococcum. Not only the colony amounts of these two species of nitrogen-fixing
      bacteria increased, grown on agar medium containing lower concentrations of
      trifluralin, but also these colonies also enlarged in size and appeared obviously
      in shorter formation time. However, trifluralin at higher concentrations would
      inhibit the development of microbial colonies both in amount and size.
      Trifluralin inhibited the activity of acetylene reduction of A. chroococcum when
      it was added at the same time of inoculation with A. chroococcum, but it showed a
      noteworthy stimulation to nitrogen fixation of A.chroococcum when it was put into
      culture after the cells of the nitrogen-fixing bacterium had grown well. The
      observation that soil microorganisms could use trifluralin as sole carbon and
      nitrogen resources for their growth, indicated that microorganisms could
      decompose trifluralin well.

PMID- 11599722
TI  - Effects of butachlor on microbial populations and enzyme activities in paddy
      soil.
AB  - This paper reports the influences of the herbicide butachlor (n-butoxymethlchloro
      -2', 6'-diethylacetnilide) on microbial populations, respiration, nitrogen
      fixation and nitrification, and on the activities of dehydrogenase and hydrogen
      peroxidase in paddy soil. The results showed that the number of actinomycetes
      declined significantly after the application of butachlor at different
      concentrations ranging from 5.5 microg g(-1) to 22.0 microg g(-1) dried soil,
      while that of bacteria and fungi increased. Fungi were easily affected by
      butachlor compared to the bacteria. The growth of fungi was retarded by butachlor
      at higher concentrations. Butachlor however, stimulated the growth of anaerobic
      hydrolytic fermentative bacteria, sulfate-reducing bacteria (SRB) and
      denitrifying bacteria. The increased concentration of butachlor applied resulted
      in the higher number of SRB. Butachlor inhibited the growth of hydrogen-producing
      acetogenic bacteria. The effect of butachlor varied on methane-producing bacteria
      (MPB) at different concentrations. Butachlor at the concentration of 1.0 microg
      g(-1) dried soil or less than this concentration accelerated the growth of MPB,
      while at 22.0 microg g(-1) dried soil showed an inhibition. Butachlor enhanced
      the activity of dehydrogenase at increasing concentrations. The soil
      dehydrogenase showed the highest activity on the 16th day after application of
      22.0 microg g(-1) dried soil of butachlor. The hydrogen peroxidase could be
      stimulated by butachlor. The soil respiration was depressed during the period
      from several days to more than 20 days, depending on concentrations of butachlor
      applied. Both the nitrogen fixation and nitrification were stimulated in the
      beginning but reduced greatly afterwards in paddy soil.

PMID- 11599723
TI  - Macroporosity and manure influence on atrazine transport through soil.
AB  - The influence of soil macro-porosity and manure on atrazine (6-chloro-N-ethyl-N'
      (1-methylethyl)-1,3,5-triazine-2,4-diamine) transport was investigated under
      laboratory conditions using disturbed and undisturbed soil columns. The macro
      porosity in the soil column was obtained with CT scanning technique. Liquid
      manure was applied at the surface of soil column, 19 cm long and 8 cm in
      diameter, at a rate of 60 m3/ha. Experimental results revealed that atrazine
      moves faster through the soils in the presence of manure compared to soil without
      application of manure. The average time for elusion and the relative peak
      concentration in the disturbed soil column without manure was 14.5 h and 3.1%,
      respectively compared to 11.0 h and 6.9% in the presence of manure, respectively.
      Similar behavior was observed in the case of disturbed soil columns. Soil macro
      porosity has shown large impact on atrazine transport, especially in the presence
      of manure.

PMID- 11599724
TI  - The effect of simulated rain on folpet and mancozeb residues on grapes and on
      vine leaves.
AB  - Artificial rainfalls were used to determine the effect of the amount of the
      rainfall and the time interval between pesticide application and rainfall event,
      on folpet and mancozeb residues on grapes and vine leaves. Forty-five mm of rain
      were administered to the vineyard in different amounts (45; 30+15; 15+15+15 mm).
      Folpet showed good rainfastness on the grapes and on the leaves. A modest
      decrease was observed only in the experiments that had received 45 mm of rain at
      one go. Mancozeb showed a lower rainfastness, since a portion of the deposit was
      easily washed off also by a modest rainfall. The percentage of this portion was
      higher in the grapes (38%) than in the leaves (20%). The data obtained in these
      experiments show that, in the case of folpet, it is not necessary to repeat the
      treatment when it rains the day after, while it is recommendable to repeat it in
      the case of mancozeb.

PMID- 11599725
TI  - Assessment of imidacloprid in Brassica environment.
AB  - Imidacloprid was applied as seed treatment (Gaucho 70 WS, 5 and 10 g ai kg(-1)
      seed) and foliar spray (Confidor 200 SL, 20 and 40 g ai ha(-1)) at 50% pod
      formation stage on mustard (Brassica campestris Linn.) to control mustard aphid,
      Lipaphis erysimi Kalt. It was detectable upto 82 and 96 days in plants after
      sowing from lower and higher doses of seed treatment. However, it dissipated
      faster and became nondetectable after 7 and 15 days of foliar treatments from
      lower and higher rates of application, respectively. The dissipation models
      yielded the rate constants of 0.0209 and 0.0230 and 0.0736 and 0.0779 day(-1)
      from seed and foliar treatment. The corresponding half-lives of 14.40 and 13.07
      and 4.09 and 3.86 days were recorded. This suggested that the dissipation was
      independent of initial doses and followed a first order rate kinetics. The
      projected TMRC of imidacloprid from seed (0.136 and 0.225 mg person(-1) day(-1))
      and foliar (0.069 and 0.1497 mg person(-1) day(-1)) treatments were found lower
      than the MPI (3.135 mg person(-1) day(-1)). At harvest mustard grains did not
      contain imidacloprid residues. The absence of imidacloprid in 0-10 and 10-20 cm
      soil layers indicated no leaching of insecticide. Therefore, imidacloprid
      treatments could be taken as safe for crop protection, consumption of leaves and
      environmental contamination point of view.

PMID- 11599726
TI  - QSAR modeling of bioconcentration factors in fish based on fragment constants and
      structural correction factors.
AB  - The quantitative structure-activity relationship between the BCF and fragment
      constant of organic chemicals was studied using a database containing 337
      experimental BCF values. The database covered a large variety of chemicals
      ranging from the very hydrophobic to the very hydrophilic with logKow values
      between 0.39 and 8.60. The structural features affecting the BCFs were identified
      and evaluated during a preliminary modeling. A final linear multivariate
      regression model was derived that was able to account for as much as 98.0% of the
      variation in the experimental BCF values. The mean absolute error for the final
      model was 0.315 log-units. In addition, the predictability and robustness of the
      model was also evaluated.

PMID- 11599727
TI  - Changes in lipids and sterols during composting.
AB  - Pyrolysis-gas (Py-GC) chromatography was used to characterize organic [(diethyl
      ether (DEE) and chloroform (CHCl3)] extracts of raw and composted duck excreta
      enriched wood shavings from two finishing cycles (C1 and C2). Materials were
      collected on days 0, 8 and 23. C1 contained 1.7 % total N while C2 contained 0.9
      % total N. Py-GC-MS (mass spectrometry) showed that the extracts contained n
      alkanes (C12 to C32), alkenes (C12:1 to C33:1), n-fatty acids (C12 to C28),
      unsaturated fatty acids (C18:1 and C18:2), and sterols (cholestene,
      cholestadiene, stigmastene, stigmastadiene, stigmastatriene, cholesterol,
      stigmastanol, stigmastanone, stigmastadienone, 17-methyl dialkylsulfanyl
      decahydro-1H-cyclopenta [a] phenanthrene, 17-methyl dialkylsulfanyl dodecahydro
      1H-cyclopenta [a] phenanthrene, and 17-methyl-17-dialkylsulfanyl decahydro-1H
      cyclopenta [a] phenanthrene). Other components identified were prystene, squalene
      (precursor of cholesterol), phthalic acid, diphenylpropane, diphenylbut-2-ene and
      1,3,6 triphenyl hex-4-ene. Our data showed significant changes in the lipid
      composition of duck excreta enriched wood shavings during composting, which
      appeared to be related to the total N content of the system.

PMID- 11599728
TI  - Ammonia removal from compost leachate using zeolite. II. A study using continuous
      flow packed columns.
AB  - Bench-scale packed zeolite columns were set up and operated to investigate the
      continuous removal of ammonium ions from compost leachate. The effects of
      hydraulic retention time (HRT), and particle size of the zeolite on the ammonia
      adsorption capacity were studied. For both the coarse particle and the powdered
      zeolite columns, higher ammonia removal efficiencies were achieved with longer
      HRT (i.e., lower influent flow rate) tests. At the same HRT, ammonia removal
      efficiencies from tests with powdered zeolite were generally 20% higher than
      tests with the coarse particle zeolite. A HRT of 6 hours was found appropriate
      for efficient ammonia removal, and an operating capacity of 1.31 mg N/g zeolite
      was obtained. Over 98% of the ammonia input from the influent was consistently
      removed for over 5 bed volumes (BV) of compost leachate flowing through the
      zeolite column. Zeolite proved to have a great potential as a medium for ammonia
      removal in treating composting leachate.

PMID- 11599729
TI  - Utilization of agricultural waste corn cob for the preparation of carbon
      adsorbent.
AB  - In the present study, a series of activated carbons were prepared from
      agricultural waste corn cob by chemical and physical activations with potassium
      hydroxide (KOH)/potassium carbonate (K2CO3) and carbon dioxide (CO2). The effect
      of process variables such as impregnation ratio, impregnation time, activation
      temperature and soaking time of CO2 was studied in order to relate these
      preparation parameters with the physical properties of final carbon products. The
      resulting activated carbons were characterized by nitrogen adsorption-desorption
      isotherms at 77 K. The surface areas and pore volumes of carbons were estimated
      by the BET equation, the Langmuir equation and the t-plot method. Under the
      experimental conditions investigated, the main parameters in the activation of
      corn cob were found to be the impregnation ratio and activation temperature. The
      soaking time of CO2 is another important variable, which had a strong effect on
      the pore volume development. The BET surface area and total pore volume were as
      large as about 2000 m2/g and about 1.0 cm3/g, respectively. This study showed
      that the activation of agricultural waste corn cob with KOH/K2CO3 and CO2 was
      suitable for the preparation of large-surface-area activated carbons.

PMID- 11599730
TI  - Lipid peroxidation and antioxidant enzyme activity in different organs of mice
      exposed to low level of mercury.
AB  - The effects of mercuric chloride (Hg) on lipid peroxidation (LPO), glutathione
      reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and
      glutathione (GSH) levels in different organs of mice (CD-1) were evaluated. Mice
      were exposed (2 days/week) to 0.0 (control), 0.8 (low) and 8.0 (mid) and 80.0
      (high) gHg/kg/day for 2 weeks. The high dose group was excluded from the study
      due to high mortality. LPO levels in kidney, testis and epididymus at low and mid
      doses; GR and GPx levels in testis at mid dose; SOD levels in brain and testis at
      both doses, liver and epididymus at mid dose; GSH levels in testis at both doses
      were significantly increased compared to their controls. However, the GR levels
      in kidney at both doses and in epididymus at mid dose; GPx levels in kidney and
      epididymus and SOD levels in kidney at both the doses; GSH levels in epididymus
      at mid dose were significantly decreased compared to their control. Body weight
      gain and food efficiency were significantly reduced (p<0.05) in mid dose. These
      results indicated that Hg treatment enhanced LPO in all tissues, but showed
      significant enhancement only in kidney, testis and epididymus suggesting that
      these organs were more susceptible to Hg toxicity. The increase in antioxidant
      enzyme levels in testis could be a mechanism protecting the cells against
      reactive oxygen species.

PMID- 11599731
TI  - Presence of bacteriophages in animal feed as indicators of fecal contamination.
AB  - The objectives of this study were to determine if indigenous male specific and
      somatic bacteriophages could be detected in animal feeds and if isolated phages
      contained RNA or DNA. Seven fresh feeds, 2 fresh feed ingredients, 7 stored
      feeds, 2 stored feed ingredients, and 8 samples of poultry diets suspected to
      contain Salmonella spp. were enriched and spot plated for indigenous phages using
      Escherichia coli Famp and CN-13 as hosts. Bacteriophage numbers were below
      detection without enrichment, but both male specific and somatic coliphages were
      detected in all animal feeds, feed ingredients, and poultry diets after 16 h of
      enrichment, even after the samples had been stored for 14 months of storage at 
      20 C. Five out of 9 fresh feeds and 7 out of 8 stored feeds contained RNA somatic
      phages.

PMID- 11599732
TI  - Understanding the physiology of difficult, pathogenic bacteria from analysis of
      their genome sequences.

PMID- 11599733
TI  - Cytokines, chemokines and other effector molecules involved in meningococcal
      disease.
AB  - This review examines the role of cytokines and chemokines in the pathogenesis of
      meningococcal disease (MCD) and draws comparisons with studies of other forms of
      sepsis in adults and in animal models. There are many similarities but also
      discrepancies between these data. MCD is a well-defined clinical syndrome with
      identifiable onset and time of presentation. It is a reliable model in which to
      study cytokine and chemokine responses in bacterial sepsis. Such studies may lead
      to new adjunctive treatments, which can be tested to ameliorate severe MCD.

PMID- 11599734
TI  - Prevalence of cdtABC genes encoding cytolethal distending toxin among Haemophilus
      ducreyi and Actinobacillus actinomycetemcomitans strains.
AB  - The aim of this study was to investigate the presence of the three cdtABC genes
      responsible for production of cytolethal distending toxin (CDT) in Haemophilus
      ducreyi and Actinobacillus actinomycetemcomitans strains. Of 100 H. ducreyi
      strains from the culture collection of the University of Goteborg (CCUG), 27
      strains with low or intermediate cytotoxic titre (< 1 in 10(4)) and 23 of the
      remaining isolates with a high cytotoxic titre (> or = 1 in 10(4)) were selected.
      Twenty-nine strains of H. ducreyi were isolated recently from patients with
      chancroid and 50 A. actinomycetemcomitans strains from patients with
      periodontitis. The cytotoxic activity on HEp-2 cells and the presence of cdtABC
      genes were studied by cytotoxicity assay of bacterial sonicates and PCR with
      primers specific for individual cdtA, B, and C genes of H. ducreyi in bacterial
      DNA preparations, respectively. All strains that manifested a cytotoxic titre in
      sonicate > or = 1 in 100 possessed all the three cdt genes. Eighteen of the 50
      strains selected from the culture collection were negative and 32 positive for
      cdt genes. As all strains with a high cytotoxic titre gave positive PCR results,
      it can be assumed that the remaining 50 strains, which have high cytotoxic titre,
      would have been positive as well. Thus, it can be estimated that 82% of the
      culture collection strains had cdtABC genes. Similarly, 24 (83%) of 29 recent H.
      ducreyi isolates expressed the CDT activity and displayed all cdtABC genes. Forty
      three (86%) of 50 strains of the closely related A. actinomycetemcomitans,
      expressing a cytotoxic activity > or = 1 in 100, also possessed all three genes.
      Furthermore, the nucleotide sequence of the cdtABC genes was highly conserved
      among H. ducreyi strains from different geographic areas. These results indicate
      that the majority of pathogenic H. ducreyi and A. actinomycetemcomitans strains
      express a CDT activity encoded by all three cdtABC.

PMID- 11599735
TI  - Non-standard biological activities of lipopolysaccharide from Helicobacter
      pylori.
AB  - As assessed by the lipopolysaccharide (LPS)-specific chromogenic Limulus
      amoebocyte lysate (LAL) assay, Helicobacter pylori LPS extracted by the phenol
      water procedure showed full potency to coagulate LAL, as did LPS from Salmonella
      minnesota and Escherichia coli. However, pretreatment of H. pylori LPS with
      polymyxin B, which easily destroys the endotoxic activity of enterobacterial
      LPS/lipid A, had little effect on the LAL coagulation activity, although the same
      treatment of E. coli LPS markedly diminished its activity. The H. pylori LPS
      induced very weak production of nitric oxide (NO) or tumour necrosis factor (TNF)
      by murine macrophages and TNF by human peripheral whole blood in vitro in
      comparison with S. minnesota LPS. These findings indicate that H. pylori LPS has
      the unique endotoxic characteristic of retaining full LAL coagulation activity
      with polymyxin B resistance, despite losing its endotoxic potencies such as the
      ability to induce NO and TNF production.

PMID- 11599736
TI  - Chloride secretion induced by thermostable direct haemolysin of Vibrio
      parahaemolyticus depends on colonic cell maturation.
AB  - Vibrio parahaemolyticus produces a thermostable direct haemolysin (TDH) that has
      been implicated in the pathogenesis of diarrhoeal disease caused by this
      organism. In previous work, TDH induced Cl- secretion in human colonic epithelial
      cells that was dependent on the intracellular Ca2+ concentration, [Ca2+]in. This
      study investigated whether Cl- secretion induced by TDH is influenced by the
      stage of maturation of intestinal epithelial cells. Two different human colonic
      cell lines, villus cell-like Caco-2 cells and crypt cell-like T84 cells, cultured
      by different methods to obtain differentiated samples, were used. When these
      cells were exposed to butyrate, a transcriptional regulator of differentiation
      genes, or co-cultured with 18Co cells, a human colonic fibroblast cell line, they
      showed increased trans-epithelial resistance and villus cell marker enzyme
      activity. In Caco-2 cells, exposure to butyrate or co-culturing with 18Co cells
      resulted in increased TDH binding, higher short-circuit currents (Isc) and
      greater [Ca2+]in. These results suggest that sensitivity to TDH is affected by
      the stage of cellular differentiation of cultured intestinal epithelial cells.

PMID- 11599737
TI  - Comparison of antibiogram, virulence genes, ribotypes and DNA fingerprints of
      Vibrio cholerae of matching serogroups isolated from hospitalised diarrhoea cases
      and from the environment during 1997-1998 in Calcutta, India.
AB  - This study identified 17 matching serogroups of Vibrio cholerae belonging to
      serogroups other than O1 and O139 isolated from human cases and from the
      environment during a concurrent clinical and environmental study conducted in
      Calcutta, a cholera endemic area. Isolates within these matching serogroups were
      compared by various phenotypic and genotypic traits to determine if the
      environment was the source of the organisms associated with the disease. Clinical
      strains of V. cholerae were resistant to a greater number of drugs and exhibited
      multi-drug resistance compared with their environmental counterparts. Except for
      the presence of the genes for the El Tor haemolysin and the regulatory element
      ToxR in most of the strains of V. cholerae examined, non-O1, non-O139 V. cholerae
      strains lacked most of the other known virulence traits associated with toxigenic
      V. cholerae O1 or O139. Restriction fragment-length polymorphism of virulence
      associated genes, ribotypes and DNA fingerprints of strains of matched serogroups
      showed considerable diversity, although some gene polymorphisms and ribotypes of
      a few strains of different serogroups were similar. It is concluded that despite
      sharing the same serogroup, environmental and clinical isolates were genetically
      heterogeneous and were of different lineages.

PMID- 11599738
TI  - Reactivity of dog sera to whole-cell or recombinant antigens of Borrelia
      burgdorferi by ELISA and immunoblot analysis.
AB  - Enzyme-linked immunosorbent assays (ELISAs) with separate preparations of 10
      purified recombinant antigens of Borrelia burgdorferi sensu stricto were used to
      test sera from 36 dogs not vaccinated with whole cells of this agent and from
      five dogs vaccinated with whole-cell B. burgdorferi bacteria. All dogs lived in
      tick-infested areas of Connecticut and south-eastern New York state, USA. The non
      vaccinated dogs had limb or joint disorder, lameness and fever during the period
      1984-1991 and had antibodies to B. burgdorferi, as determined by a polyvalent
      ELISA with whole-cell antigen. In re-analyses of sera for total immunoglobulins
      in ELISAs with recombinant antigens, reactions were most frequently recorded when
      outer-surface protein (Osp) F, protein (p)35, p37, p39 and p-41G (a flagellin
      component) were tested separately. Western immunoblots of a subset of 16 sera,
      positive by ELISA with whole-cell antigen and representing a range of antibody
      titres (640-40960), verified immune responses to these or other lysed whole-cell
      antigens. Sera from vaccinated dogs contained antibodies to OspA, OspB, p22, p37
      and p41-G. Therefore, serological reactions to OspF, p35 and p39 were the most
      important indicators of natural exposure to B. burgdorferi. Serum reactivities to
      these recombinant antigens in ELISAs can be used to help identify possible
      natural infections of canine borreliosis in dogs not vaccinated with whole-cell
      B. burgdorferi and to provide information on the geographic distribution of this
      bacterium.

PMID- 11599739
TI  - Genotypic and phenotypic characterisation of Borrelia burgdorferi sensu lato
      strains isolated from human blood.
AB  - Lyme borreliosis often presents initially with erythema migrans. Borreliae may
      disseminate from the primary skin lesion, and different organs and systems could
      be affected. Borrelia strains were isolated from blood of 70 patients with Lyme
      borreliosis, including 10 patients from whom borreliae were also isolated from
      skin. The aim of the present study was to characterise the isolates with regard
      to their phenotypic and genotypic characteristics. Borreliae were cultivated in
      MKP medium. Species identification and plasmid profiles were determined by pulsed
      field gel electrophoresis (PFGE) and protein profiles by SDS-PAGE. Digestion of
      Borrelia burgdorferi sensu lato DNA showed 63 (90%) B. afzelii Mla1 and 7 (10%)
      B. garinii Mlg2. No B. burgdorferi sensu stricto were isolated. Borreliae were
      isolated from both skin and blood of 10 patients, nine pairs of isolates were
      identical: seven B. afzelii and two B. garinii. B. afzelii was isolated from the
      skin and B. garinii from blood of the tenth patient. All but one isolate
      possessed at least one large plasmid and varying numbers of smaller plasmids.
      Eight (11.4%) of 70 isolates possessed an unusual plasmid profile (2 of 63 B.
      afzelii and 6 of 7 B. garinii). Borreliae differed in their protein profiles.
      OspA and OspB proteins were expressed by all B. afzelii isolates; 85.7% of B.
      garinii isolates expressed OspA and 71.4% expressed OspB. OspC was expressed by
      65% of B. afzelii isolates and all B. garinii isolates. The ratios of B. afzelii
      and B. garinii isolated from blood and skin were similar. These results do not
      support the hypothesis that B. garinii has a higher propensity for haematogenous
      dissemination than B. afzelii. Antigen diversity as well as species and plasmid
      heterogeneity could play a role in the pathogenesis of the infection, suggesting
      distinctive strain organotropism.

PMID- 11599740
TI  - The prevalence of Chlamydia trachomatis in fresh tissue specimens from patients
      with ectopic pregnancy or tubal factor infertility as determined by PCR and in
      situ hybridisation.
AB  - The prevalence of chlamydial DNA determined by PCR and in-situ hybridisation
      (ISH) in fresh tissue specimens (endometrium, fallopian tube and ovary) was
      investigated in 33 women presenting with ectopic pregnancy (EP), 14 women with
      tubal factor infertility (TFI) and 50 control patients from the UK and the West
      Indies. In the UK EP group, chlamydial DNA was detected by PCR in 56% of
      patients; similar results were found in the Trinidad EP group (67%). In the TFI
      group, chlamydial DNA was detected in (71%) of patients by PCR. The detection of
      Chlamydia trachomatis DNA by ISH was highest in the TFI group (43%). Women
      presenting with EP and TFI showed evidence of previous or current genital C.
      trachomatis infection, underlining the importance of this microorganism in the
      development of these conditions. Importantly, chlamydial DNA could be detected in
      DNA preparations from the endometrium, fallopian tube and ovary of EP and TFI
      patients at the time of surgery.

PMID- 11599741
TI  - Genetic analysis of methicillin-resistant Staphylococcus aureus expressing high-
      and low-level mupirocin resistance.
AB  - Clinical strains of methicillin-resistant Staphylococcus aureus (MRSA) expressing
      high- and low-level mupirocin resistance were studied to determine the genetic
      location of mupirocin and other resistance determinants. Mupirocin resistance was
      confirmed by MIC determination with E-test strips. Curing and transfer
      experiments were used to establish the genetic location of the resistance
      determinants and the PCR with mupA-specific primers was used to detect the
      presence of mupA genes. High-level mupirocin-resistant isolates had MICs >1024
      mg/L, whereas the low-level resistant isolates had MICs of 32-128 mg/L. The
      isolates carried plasmids ranging from 2.8 to 38 kb in size. All of them carried
      26- and 3.0-kb plasmids, but only the high-level mupirocin-resistant isolates
      carried a 38-kb plasmid. Curing and transfer experiments revealed that the 26-kb
      plasmid encoded resistance to cadmium, mercuric chloride, propamidine isethionate
      and ethidium bromide and the 38-kb plasmid was a conjugative plasmid encoding
      high-level mupirocin resistance. One isolate, IBN287, carried both plasmid-borne
      high-level and chromosomal low-level mupirocin resistance. The mupA gene was
      detected on the 38-kb plasmid DNA but not in the genomic DNA of the low-level
      mupirocin-resistant isolates. The genomic DNA of strain IBN287 cured of the 38-kb
      mupirocin resistance plasmid did not contain mupA. The results suggest that
      different genes encoded low- and high-level mupirocin resistance in these
      isolates.

PMID- 11599742
TI  - Inhibition of the in-vitro growth of Mycobacterium tuberculosis by a
      phytosiderophore.
AB  - Non-compliance by patients and poor clinical management due to the use of
      incorrect regimens are the main reasons for the development of drug resistance by
      mycobacterial strains. New strategies for the control of multi-drug-resistant
      mycobacterial strains have become a necessity for proper management of
      tuberculosis, which, according to the WHO report (1997), is estimated to remain
      among the top 10 mortality-causing diseases of the twenty-first century. One of
      the strategies is the use of iron-sequestering agents like siderophores as active
      therapeutic agents in the treatment of tuberculosis. This report describes for
      the first time the inhibition of the growth of Mycobacterium tuberculosis H37Ra
      in vitro by a phytosiderophore isolated from the root washings of Tephrosia
      purpurea. This finding may help in the establishment of a new drug regimen which
      will be more effective in the treatment of tuberculosis.

PMID- 11599743
TI  - Association between cyclohexane resistance in Salmonella of different serovars
      and increased resistance to multiple antibiotics, disinfectants and dyes.
AB  - A panel of 388 salmonellas of animal and human origin, comprising 35 serotypes,
      was tested for resistance to cyclohexane and to a range of antibiotics,
      disinfectants and dyes. Cyclohexane resistance was detected in 41 isolates
      (10.6%): these comprised members of the serovars Binza (1 of 15), Dublin (1 of
      24), Enteritidis (1 of 61), Fischerkietz (4 of 5), Livingstone (9 of 11),
      Montevideo (1 of 32), Newport (4 of 23), Saint-paul (1 of 3), Senftenberg (10 of
      24) and Typhimurium (9 of 93). Most (39 of 41) of the cyclohexane-resistant
      isolates were from poultry. Statistical analysis showed that the cyclohexane
      resistant strains were significantly more resistant than the cyclohexane
      susceptible strains to ampicillin, chloramphenicol, ciprofloxacin, erythromycin,
      nalidixic acid, tetracycline, trimethoprim, cetrimide and triclosan. The
      multiresistance patterns seen were typical of those caused by efflux pumps, such
      as AcrAB. The emergence of such resistance may play an important role in the
      overall antibiotic resistance picture of Salmonella, with particular effect on
      ciprofloxacin.

PMID- 11599744
TI  - Typing of Scedosporium apiospermum by multilocus enzyme electrophoresis and
      random amplification of polymorphic DNA.
AB  - The genetic diversity among epidemiologically unrelated strains of the human
      pathogenic fungus Scedosporium apiospermum or its teleomorph, Pseudallescheria
      boydii, from different areas in Europe, was investigated by multilocus enzyme
      electrophoresis (MLEE) and random amplification of polymorphic DNA (RAPD).
      Fourteen enzyme activities were analysed by starch gel electrophoresis,
      corresponding to 27 polymorphic loci and 43 iso-enzymes. Among the enzymes
      studied, propionate esterase, carboxyl esterase, superoxide dismutase, carbonate
      dehydratase and malate dehydrogenase were the most polymorphic, allowing the
      classification of the strains into 6-11 groups each. Combination of the data
      obtained for the different enzyme activities studied allowed differentiation of
      the strains. Similarly, a high polymorphism was also revealed by each of the 20
      RAPD primers tested, but no single primer was able to differentiate all the
      strains. The most efficient primers were GC70, UBC-701 and UBC-703, which
      revealed 17 distinct genotypes each, and combination of the results obtained with
      this three-primer set allowed complete discrimination of the strains. The
      dendrograms obtained from MLEE or RAPD by the unweighted pair-group method using
      arithmetic average cluster analysis did not reveal any clustering according to
      the geographic origin of the strains or their pathogenicity.

PMID- 11599745
TI  - The occurrence of campylobacteriosis in domestic animals and their handlers in
      and around Calcutta.

PMID- 11599746
TI  - A case of Campylobacter jejuni peritonitis in a patient undergoing peritoneal
      dialysis.

PMID- 11599747
TI  - Possible mechanism for the enhanced lethality of an interleukin-4-expressing
      mousepox virus.

PMID- 11599748
TI  - Risk factors for long-term treatment of whiplash injury in Japan: analysis of 400
      cases.
AB  - We studied the risk factors for long-term treatment of 400 patients with whiplash
      injury in Japan. Most of the patients were injured in rear-end car collisions,
      but none had cervical bone lesions or spinal cord or root lesions. We evaluated
      the following risk factors: sex, age, degree of vehicle damage, and admission or
      non-admission to the hospital. The group of patients younger than 20 years old
      healed more quickly than patients 30 years or older. Damage to more than half of
      the car was associated with a longer treatment. Patients who were admitted to the
      hospital need treatment longer than the non-admission group. Thus, age over 30
      years, a large amount of damage to the vehicle, and admission to the hospital are
      predictors of long-term treatment for whiplash injury in Japan.

PMID- 11599749
TI  - The post-discectomy syndrome. Aetiology, diagnosis, treatment, prevention.
AB  - The post-discectomy syndrome (PDS) is a common diagnosis in patients with
      problems following a disc operation. The different causes of PDS make the
      establishment of the correct diagnosis and its corresponding efficient treatment
      difficult. A general overview published in the bibliographical data covering the
      entity of PDS is rare. The following paper aims to specify PDS according to its
      aetiology, diagnosis, treatment and prevention. The diagnosis should be made
      efficiently, so that the patient can receive prompt adequate therapy.

PMID- 11599750
TI  - Horse-related injuries in a thoroughbred stabling area in Japan.
AB  - To investigate the demographic details and patterns of injuries related to horse
      handling, we reviewed 637 horse-related injuries in 581 stable- or stud-workers
      in a representative area of thoroughbred stabling in Japan. We found that (1)
      injuries occurred most frequently in a group of a relatively young workers, with
      a seasonal variation; (2) the principal mechanism of injury was kicks, which
      accounted for 39.2% of all injuries, including 11 serious and one lethal visceral
      injuries; (3) the upper half of the body was more frequently involved than the
      lower half; and (4) the peripheral bones (hand and foot) and the ribs accounted
      for more than half of 148 fractures. These findings are distinct from those in
      horse-riding injuries reported in the literature and emphasize the importance in
      developing preventive strategies specifically for workers in horse stables.

PMID- 11599751
TI  - Avascular necrosis of femoral head after gamma-nailing for unstable
      intertrochanteric fractures.
AB  - We reported on 7 cases of avascular necrosis of the femoral head after treatment
      of an unstable intertrochanteric fracture with the Asian Pacific gamma-nail. The
      incidence was about 1.16% (7 of 604) in our series. Good reduction and good
      implant position were achieved in all 7 men. Avascular necrosis was found about 6
      months to 3 years after the initial operation, and all the fractures were solidly
      united at the final diagnosis. The possible etiologies were initial high energy
      trauma and combining basal neck fracture and iatrogenic damage of the blood
      supply to the femoral head.

PMID- 11599752
TI  - New evaluation method using preoperative magnetic resonance imaging for cervical
      spondylotic myelopathy.
AB  - A new method based on the score of preoperative magnetic resonance images (MRI)
      was devised to evaluate cervical spondylotic myelopathy and predict the results
      of cervical laminoplasty. On T1- and T2-weighted sagittal MRI, the intervertebral
      disc spaces at each level from the axis to the first thoracic spine were examined
      as to whether the anterior or posterior subarachnoid space would be maintained or
      not, and for the presence or absence of spinal cord deformity. The data were
      divided into six grades and rated, and the total score for all sites was regarded
      as the preoperative MRI cumulative score. In conclusion, our method was highly
      reliable and useful for a preoperative evaluation and prediction of results after
      cervical laminoplasty for cervical spondylotic myelopathy.

PMID- 11599753
TI  - Biomechanical evaluation of hip joint after Salter innominate osteotomy: a long
      term follow-up study.
AB  - The biomechanical state of the hip after a Salter innominate osteotomy was
      investigated by using the radiographic data of 38 operated and 21 contralateral
      nonoperated hips from our archives. The centre-edge angle of Wiberg was
      determined from the radiographs taken shortly after the operation. From the
      radiographs of the latest follow-up (7-13 years after the operation), we also
      determined the peak value of contact hip joint stress normalized by the body
      weight, and the functional angle of the weight-bearing area. A mathematical model
      was used. We show that the geometrical parameters aside from the centre-edge
      angle may considerably influence the contact hip stress distribution. We also
      show that the functional angle of the weight-bearing area is a more relevant
      parameter than the normalized peak stress if the exact magnification of the
      images is not known and if there is considerable variation of the image size
      within the sample. The development of the centre-edge angle of the operated hips
      and of the contralateral hips was also studied. We found that the centre-edge
      angle increases on average during the follow-up time in the operated hips as well
      as in the contralateral nonoperated hips, but the average increase is smaller in
      the former. It is shown that an unfavorable stress distribution is connected to
      the decrease of the centre-edge angle over time. Finally, we found a weak
      positive correlation between the centre-edge angle shortly after the operation
      and the functional angle of the weight-bearing area at the of the latest follow
      up.

PMID- 11599754
TI  - Transpedicular decancellation osteotomy in the treatment of peridural fibrosis.
AB  - From 1992 to 1997 a series of 12 multiply operated (averaging 2.5 previous
      operations) patients with recurrent peridural fibrosis and postlaminectomy
      kyphosis underwent surgery at our clinic. The surgery was designed to restore the
      physiological lordosis and relax tethered cord and epidural veins by
      transpedicular decancellation osteotomy at a vertebra other than the vertebra
      with peridural fibrosis. This paper presents the long-term functional outcome of
      these 12 patients. Clinical assessments were conducted pre-operatively and at 3
      month intervals postoperatively and included X-ray assessment and evaluation of
      the patients' functional status by Oswestry Disability Index (ODI) and of pain by
      visual analogue scale (pain VAS). All symptoms and the pain due to peridural
      fibrosis disappeared in the early postoperative period. Patients had tower
      disability and pain scores at their early and long-term follow-ups (follow-up
      period 24-74 months, mean 36.3 months). For patients with failed medical therapy
      for peridural fibrosis accompanied by lumbar kyphosis or hypolordosis,
      transpedicular decancellation osteotomy should be the surgical treatment of
      choice.

PMID- 11599755
TI  - Acute septic arthritis of the hip in children.
AB  - Thirty-three cases of acute septic arthritis of the hip in children were treated
      at our hospital from 1986 to 1997. The average follow-up period was 6 years
      (range 2-11 years). In 17 cases the right hip was affected, and in 16 the left
      hip. The average duration of symptoms was 5 days (range 1-14 days).
      Microorganisms were isolated from the blood, joint aspirate, or surgical
      specimens in 25 cases (76%). Staphylococcus aureus was the most common bacteria
      found (44%). Those patients with S. aureus infection were older than 1 year of
      age. There was no significant difference in the final outcome between the younger
      and the older age groups. Twenty-six out of 33 patients (89%) had a satisfactory
      outcome. Satisfactory results can also be expected with arthrocentesis and
      medical treatment if the diagnosis is made early, and antibiotic treatment
      affords a good clinical response. Four out of 7 cases with an unsatisfactory
      result were associated with osteomyelitis of the proximal femur. The two most
      important factors associated with poor results included a delay of definite
      treatment lasting longer than 5 days and the presence of osteomyelitis of the
      proximal femur.

PMID- 11599756
TI  - Complications of K-wire fixation of fractures and dislocations in the hand and
      wrist.
AB  - Kirschner wire (K-wire) fixation of fractures and dislocations of the hand and
      wrist is a common procedure. Of the 590 K-wire fixations performed on 236
      patients, 36 (15.2%) experienced complications which included osteomyelitis,
      tendon rupture, nerve lesion, pin tract infection, pin loosening or migration.
      There were no deep soft-tissue pin infections or pyarthrosis. Technical failure,
      mainly when the procedure was performed by residents, and poor patient compliance
      were the major causes of complications. K-wire fixation is a simple but demanding
      procedure that cannot be left to an inexperienced resident. Elimination of
      technical failure, supervision in the operating room, close monitoring, prompt
      treatment upon discovery of a complication, and improvement of patient compliance
      can reduce the rate of complications.

PMID- 11599757
TI  - Risk factors for heterotopic ossification in total hip arthroplasty.
AB  - This study prospectively evaluated 928 patients with 1318 primary total hip
      replacements for heterotopic ossification (HO). The mean clinical and
      radiological follow-up was 2.5 years (range 1.5-3.6 years). HO was noted in 44.6%
      of all total hips replaced. It was graded as mild (Brooker 1) in 29.2%, moderate
      (Brooker 2) in 10.5%, and severe (Brooker 3 and 4) in 4.2%. The following factors
      showed a significantly increased risk of HO: hypertrophic osteoarthritis, HO
      after contralateral total hip replacement, trochanteric osteotomy, lateral or
      anterolateral approach, previous hip surgery, subtrochanteric femoral osteotomy,
      and male gender (p < 0.05 in chi-square analysis of independence and
      multivariable analysis). Patients with rheumatoid arthritis showed less HO. A
      combination of any of these factors resulted in a significant increase in the
      risk of developing HO.

PMID- 11599758
TI  - Ultrasonography as a diagnostic modality in Osgood-Schlatter disease. A clinical
      study and review of the literature.
AB  - Sonographic examination of the knee has been proposed by several authors in the
      past as a simple and reliable method to diagnose Osgood-Schlatter disease (OSD).
      Ultrasound was used to compare the knees of 25 boys and 10 girls with typical OSD
      with 35 symptom-free knees of an aged-matched group of children. Based on
      recorded data, patients were categorized (one affected knee in each individual)
      according to the classification system proposed by De Flaviis et al. in 1989. The
      results included the following pathological findings: pretibial swelling,
      fragmentation of the ossification center, insertional thickening of the patellar
      tendon, and excessive fluid collection in the infrapatellar bursa. Of our
      patients, 26% fell into the type 1 category, 43% were type 2, 20% type 3, and 11%
      type 4. This distribution of cases was found to be statistically similar to the
      initial findings reported by De Flaviis and colleagues. This study therefore
      supports the validity and reproducibility of their classification method for the
      ultrasonographic evaluation of children with OSD. This is only the first step,
      and further assessment of this classification is still required to elucidate its
      clinical as well as its prognostic value.

PMID- 11599759
TI  - Glomus tumors with cystic changes around the ankle.
AB  - Sizable glomus tumors with cystic changes in the ankle are extremely uncommon.
      This paper describes painless glomus tumors with cystic changes arising in the
      ankle of a 22-year-old woman. At the age of 14, a painless mass was noticed on
      the lateral side of the left ankle, and at age 21, another mass appeared on the
      medial side of the same ankle. Magnetic resonance imaging (MRI) and computed
      tomography (CT) scanning revealed 4.5 x 4.0 cm and 2.0 x 2.0 cm sized masses on
      the medial side and a 3.0 x 4.0 cm sized cystic mass on the lateral side of the
      ankle. The tumors were removed en bloc. Microscopically, the tumor consisted of
      perivascularly arranged cells with punched-out, round, and regular nuclei.
      Immunohistochemically, the tumor cells expressed SMA and HHF-35, indicating
      smooth muscle cell characters. The patient had no recurrence at 2 years after
      surgery.

PMID- 11599760
TI  - Entrapment and transection of the median nerve associated with minimally
      displaced fractures of the forearm: case report and review of the literature.
AB  - Complete transection of the median nerve associated with minimally displaced
      fractures of forearm bones is described in a 20-year-old woman. An end-to-end
      epineural repair was performed. There was good sensory and motor recovery of the
      median nerve in the hand.

PMID- 11599761
TI  - Osteonecrosis of the accessory navicular bone.
AB  - A case of osteonecrosis of the accessory navicular bone is reported. This entity
      should be kept in mind in the differential diagnosis of painful accessory
      navicular.

PMID- 11599762
TI  - Forensic significance of concentrations of ethanol in brain tissues following
      induced acute subdural hemorrhage.
AB  - The concentrations of ethanol in peripheral blood, subdural hematomas and various
      regions of the brain were determined 1, 2, 4, and 6 h after the induction of a
      hemorrhage into a subdural space in the right temple of rabbits. The
      concentrations were compared to cases of intravenous administration of ethanol
      free i.v. fluid. Concentrations of ethanol in the subdural hematomas gradually
      decreased to correspond to those in the peripheral blood. The influence of an
      intravenous infusion of ethanol-free i.v. fluid was not observed. Concentrations
      in the brain of the right temporal, parietal and frontal lobes were high and
      those in the right temporal lobe were maintained during the 6 h of our
      experiment. Therefore, to determine if a human victim was under the influence of
      ethanol at the time of injury, we recommend that brain concentrations of ethanol
      be determined. This is apparently the first study to confirm that the estimation
      of ethanol in the brain provides a more accurate determination of how much
      ethanol had been ingested.

PMID- 11599763
TI  - Paternity testing using Y-STR haplotypes: assigning a probability for paternity
      in cases of mutations.
AB  - In parentage testing with male children, Y-chromosomal STR evidence is gaining
      more and more importance. In some cases, multilocus haplotypes of related persons
      can differ at a single locus due to a mutation. In this work, a likelihood
      approach is presented for the calculation of a probability for paternity under
      consideration of a single mutation event on the Y-chromosome. The new methodology
      is applied to two case examples.

PMID- 11599764
TI  - Trajectory reconstruction from trace evidence on spent bullets. I. Deposits from
      intermediate targets.
AB  - Contact of a fired bullet with an intermediate target of sufficient resistance
      commonly causes the bullet to ricochet, fragment or perforate together with a
      deviation in trajectory. The transfer of intermediate target material to bullets
      and subsequent detection on the bullet surface after recovery from a bullet
      collector, were examined using a scanning electron microscope and an energy
      dispersive X-ray spectrometer (SEM/EDS). A total of 76 gunshots (9 mm Luger FMJ
      RN bullets) were fired at various intermediate targets and at combinations of
      intermediate targets and tissue located in line. Elements already present on
      unfired bullets and elements from the bullet collector, the jacket, the charge
      and primer could be consistently detected as a "background". Abundant deposits of
      "fragile" (brittle) materials such as concrete, flat glass, asphalt and gypsum
      board could be visualised on every bullet by SEM. The transfer dynamics involved
      a direct imprint of target material on the bullet surface and thus preferential
      locations at the tip but also indirect deposition over the entire surface
      ("powder effect"). X-ray microanalysis demonstrated matching spectra of the
      elemental composition of these deposits and of the targets contacted. After
      perforation of "ductile" (flexible) materials such as wood and car body parts,
      the deposits on the bullets did not show characteristic spectra. If multi-layered
      car metal targets were hit, few and uncharacteristic fragments were scattered
      over the bullet surface and titanium indicative of paint-work could be determined
      on only a minority of bullets. The elemental composition of wood itself was
      heterogeneous but the fibrous morphology of the deposits was typical. The SEM/EDS
      findings in gunshots including subsequent perforation of tissue were similar. In
      particular, the trace evidence primarily transferred to the bullets was not
      eliminated by secondary contact and the determination of the fragile target
      materials was not affected. So when a person is killed or injured by a gunshot,
      the presence of a ricochet and the target material can be determined. This
      possibility needs to be considered before an evidential bullet is cleaned or
      contaminated.

PMID- 11599765
TI  - Immunohistochemical alterations after intravital and post-mortem traumatic
      myocardial damage.
AB  - Two series of experiments have been carried out on heart tissue for the
      occurrence of post-mortem and intravital myocardial damage. The first series was
      carried out on 18 porcine hearts collected immediately after the pigs were killed
      in a slaughterhouse. The hearts were subjected to stab wounds post-mortem,
      varying between 5 min and 140 min after death. The second series investigated
      were human hearts with intravital damage, i.e. 4 stab wounds, 1 gunshot, 13
      contusions and ruptures. The time the trauma occurred before death varied between
      0 and 30 min. The investigation comprised the four myocyte structural proteins
      myoglobin, FABP, troponin C, desmin and the three plasma proteins fibrinogen,
      fibronectin and C5b-9. Both series exhibited a variety of direct traumatic
      changes with a much broader zone in vital damage compared to post-mortem damage.
      In vital damage the zone of direct damage is in continuity with a further zone of
      indirect damage which is a three dimensional network. The signs of damage are
      contraction bands, depletion of structure antigens, contraction-associated
      accumulation of structure proteins, accumulation of plasma proteins on the cell
      surfaces and in the interstitium. In vital damages there is in addition an
      intrasarcolemmal accumulation of plasma proteins. The pattern of all damage is
      much broader and much more variegated in vital damage, thus vital damage can be
      clearly differentiated from post-mortem damage. bin, heart-type fatty acid
      binding protein (FABP), troponin, desmin, fibrinogen and fibronectin (Amberg
      1995; Brinkmann et al. 1993; Glatz et al. 1994; Kleine et al. 1993; Leadbetter et
      al. 1989; Ortmann et al. 2000a, 2000b; Osuna et al. 1998; Thomsen and Held 1994,
      1995). The aim of the present study was to elaborate reaction patterns of these
      marker proteins in mechanical heart trauma induced ante- and post-mortem and to
      explore their value for wound age determination in forensic casework.

PMID- 11599766
TI  - An annotated mtDNA database.
AB  - We have compiled a database of mitochondrial DNA (mtDNA) control region,
      hypervariable regions 1 (HVR1) and 2 (HVR2) sequences of a total of 14,138
      individuals compiled from 103 mtDNA publications before 1 January 2000, 13 data
      sets published in 2000 and 2001 and 2 unpublished data sets of Iraqi Kurds and
      Indians from Kerala. By contacting the authors and by other means, we have
      confirmed and corrected sequence errors, eliminated duplications and harmonised
      the sequence format. These changes affected all but 26 of the 116 publications.
      Furthermore, we have implemented a geographic information system ("mtradius")
      which searches for closest matches to a given mtDNA control region sequence and
      displays them on a geographic map. A potential application is to estimate a
      chance matching probability when a forensic stain and a suspect have an identical
      mtDNA sequence: we suggest that the geographic area with the highest frequency of
      closely related mtDNA sequence types may be used to define a reference population
      to give the suspect the maximum benefit of doubt in accordance with the ceiling
      principle.

PMID- 11599767
TI  - Flemish population data and sequence structure of the hypervariable
      tetranucleotide repeat locus D12S1090.
AB  - The allele frequency and sequence structure of the STR locus D12S1090 were
      investigated in 598 Flemish individuals. The locus shows a complex organisation
      with repetitions of GATA interrupted by TA and other tetra- and pentanucleotide
      blocks. No deviation from Hardy-Weinberg equilibrium was observed. The extensive
      polymorphism makes it a powerful tool for identity as well as paternity testing
      and even permits differentiation of closely related populations, such as Flemish
      and Germans. D12S1090 seems to be one of the most informative STRs, however, as
      seen in other highly variable STRs, the observed mutation frequency of 5.1 x 10(
      3), is relatively high. of STR loci is typing highly polymorphic STRs such as
      ACTBP2 [3]. We thus investigated the tetranucleotide (GATA) repeat locus D12S1090
      (GDB accession number GDB:376560, also known as GATA5A09) in a population sample
      from Flanders, the Dutch speaking part of Belgium. Although this STR is
      considered to be highly polymorphic [4], compared with other STRs, it has only
      scarcely been studied.

PMID- 11599768
TI  - Non-amplification of an allele of the D8S1179 locus due to a point mutation.
AB  - During a population study of 128 Korean families (626 persons) with the AmpF/STR
      Profiler Plus PCR amplification system, we found an unusual homozygous genotype
      at the D8S1179 locus in 4 families. Therefore, a new pair of primers was designed
      for the D8S1179 locus from GenBank data (GenBank Accession No. G08710) to
      evaluate the cause. The newly designed primers amplified alleles that were not
      amplified with the AmpFlSTR Profiler Plus PCR amplification system. We sequenced
      alleles of the family members who had non-amplified alleles and we found a G-to-A
      transition at the position of the 147th base of the GenBank sequence.

PMID- 11599769
TI  - The evaluation of mixed stains from different ethnic origins: general result and
      common cases.
AB  - In some situations, it can be inferred from the crime circumstances that the
      mixed stain donors are of different ethnic groups. The evaluation of DNA mixtures
      with contributors coming from more than one ethnic group is considered under the
      assumption of independence of alleles within and between ethnic groups. A general
      formula is derived for the assessment of the weight of evidence in mixed stain
      problems. This formula is equivalent to that of Fukshansky and Bar, but we give a
      different derivation. For the convenience of practitioners, the explicit
      expressions of the likelihood ratios for 14 common cases are presented. The
      effect of different ethnic groups to the assessment of the evidence is shown in
      the well-known Simpson case.

PMID- 11599770
TI  - Identification and characterization of two novel human polymorphic STRs on the Y
      chromosome.
AB  - From sequence database information, we have identified two male-specific and
      polymorphic tetranucleotide STRs, DYS 441 (GDB:10013873) and DYS 442 (GDB:
      10030304), on the Y chromosome. Analysis of 184 males allowed 7 and 5 alleles to
      be distinguished in the DYS 441 and DYS 442 systems, respectively, yielding 21
      haplotypes. The gene diversities were 0.72 and 0.51, respectively and the
      haplotype diversity was 0.85.

PMID- 11599771
TI  - Multiplex PCR amplification of eight STR loci in Austrian and Croatian Caucasian
      populations.
AB  - Austrian and Croatian Caucasian population data were generated for eight
      tetrameric STR loci amplified in a single multiplex reaction. Fluorescent
      detection was employed using the ABI Prism 310 Genetic Analyzer, the 377 DNA
      Sequencer (ABI) and the 373A DNA Sequencer (ABI). The loci analyzed were
      HUMvWFA31 (vWA), HUMTH01, HUMTPOX, HUMCSF1PO, D5S818, D13S317, D7S820 and D16S539
      as part of the GenePrint PowerPlex multiplex system.

PMID- 11599772
TI  - Intranuclear ubiquitin immunoreactivity of the pigmented neurons of the
      substantia nigra in fatal acute mechanical asphyxiation and drowning.
AB  - To evaluate the significance of immunohistochemical staining of ubiquitin (heat
      shock protein) in the midbrain for the medico-legal diagnosis of fatal
      asphyxiation and drowning, we investigated forensic autopsy cases of fatal
      mechanical asphyxia (n = 18), manual/ligature strangulation (n = 9), hanging (n =
      4), aspiration/choking (n = 5) and drowning (n = 16). These were compared to
      control groups (n = 30) consisting of fatalities from brainstem injury (n = 12)
      and acute myocardial infarction (n = 18). Ubiquitin was clearly demonstrated in
      the nuclei of pigmented substantia nigra neurons, showing two intranuclear
      staining patterns: a type of inclusion (possibly Marinesco bodies) and a diffuse
      staining. The diffuse staining was significantly more frequently observed in
      cases of drowning. The percentage of total ubiquitin positive neurons was
      frequently higher in strangulation (5.1-28.4%, mean 17.0%), aspiration/choking
      (5.3-32.0%, mean 17.6%) and drowning (7.0-34.1%, mean 19.8%), but relatively low
      in hanging (5.1-12.7%, mean 8.6%), brainstem injury (0-10.4%, mean 5.0%) and
      acute myocardial infarction (1.5-16.9%, mean 8.3%). These observations suggest
      that intranuclear ubiquitin immunoreactivity of the pigmented substantia nigra
      neurons in the midbrain was induced by a fatal severe stress on the central
      nervous system in asphyxiation and drowning.

PMID- 11599773
TI  - Summary of final report: Space Life Sciences Planning Workshop (SLSPW). June 5-7,
      2000 Mont Tremblant, Quebec.
AB  - A Space Life Sciences Planning Workshop was sponsored by the Canadian Space
      Agency to identify key questions in the major research areas supported by the
      Life Sciences Program, to identify Canadian strengths and capabilities as they
      relate to these research areas, and to make recommendations for the future
      directions of the Life Sciences Program. The conclusions reached by the workshop
      participants have been presented to the Canadian Space Agency. This report is a
      summary of those conclusions.

PMID- 11599774
TI  - Effects of 4-hydroxyandrostenedione and hyperstimulation with pregnant mare serum
      gonadotrophin on early embryonic development in rats.
AB  - A possible role of high oestradiol levels in mediating the adverse effects of
      hyperstimulation with pregnant mare serum gonadotrophin (PMSG) on early embryonic
      development in the rat was investigated using an aromatase inhibitor, 4
      hydroxyandrostenedione (4-OHA), to inhibit endogenous oestradiol production.
      Three experiments were conducted in this study. In the first, varying doses of 4
      OHA were administered either concurrently with human chorionic gonadotropin (hCG)
      to pro-oestrus female rats hyperstimulated at early di-oestrus stage with 20 IU
      PMSG or alone into nonhyperstimulated pro-oestrus females. At high doses of 1000,
      2000, or 5000 microg/rat, 4-OHA substantially improved the survival of embryos in
      hyperstimulated females, while low doses of 100 and 500 microg/rat were
      ineffective. The protective effect of 4-OHA on embryo count was optimum at 2000
      microg. When administered alone, only the highest dose of 5000 microg/rat 4-OHA
      increased embryo count. In the second experiment, higher doses of PMSG were
      studied (30 or 40 IU), with or without 5000 microg/rat 4-OHA given at the time of
      hCG injection. PMSG proved to be more detrimental with increasing dose, and 5000
      microg/rat 4-OHA was able to rescue embryos from death in the 30, but not 40,
      PMSG group. In the third experiment, the influence of the timing of 4-OHA
      treatment on its ability to improve the embryo count in hyperstimulated females
      was examined by introducing 4-OHA 24 h earlier, rather than at the time of hCG
      treatment. The results showed the importance of timing of 4-OHA administration,
      as 5000 microg/rat 4-OHA was able to restore embryo survival in the 40 PMSG
      hyperstimulated group only when it was administered 24 h before hCG injection.
      Together, these results highlighted that 4-OHA, when administered at the
      appropriate time and dose, could reverse the negative effects of hyperstimulation
      from PMSG on early embryonic development. This may be due to its potent aromatase
      inhibiting properties that lead to the suppression of oestrogen production,
      thereby alleviating the supraphysiological level of oestradiol, which is
      typically present in PMSG-treated females. Interestingly, 4-OHA treatment on its
      own was able to positively influence embryo count when given at a high dose of
      5000 microg/rat, and this may be associated with its weak androgenic properties.
      In conclusion, this study supports the hypothesis that excessive oestradiol is
      responsible for the negative effects of hyperstimulation with PMSG on early
      embryonic development.

PMID- 11599775
TI  - Mechanical, biochemical, and morphological changes in the heart from chronic food
      restricted rats.
AB  - Food restriction (FR) has been shown to induce important morphological changes in
      rat myocardium. However, its influence on myocardial performance is not
      completely defined. We examined the effects of chronic FR on cardiac muscle
      function and morphology. Sixty-day-old Wistar-Kyoto rats were fed a control (C)
      or a restricted diet (daily intake reduced to 50% of the amount of food consumed
      by the control group) for 90 days. Myocardial performance was studied in isolated
      left ventricular (LV) papillary muscle. Fragments of the LV free wall were
      analysed by light microscopy, and the ultrastructure of the myocardium was
      examined in the LV papillary muscle. The myocardial collagen concentration was
      also evaluated. FR decreased body weight (BW) and LV weight (LVW); the LVW/BW
      ratio was higher in the restricted group (C, 1.86+/-0.17 mg/g; FR, 2.19+/-0.31
      mg/g; p < 0.01). In the FR animals, the cardiac fibers were polymorphic, some of
      them were of small diameter and others presented lateral infoldings; the
      ultrastructural alterations were focal and included reduction of sarcoplasmic
      content, absence and (or) disorganization of myofilaments and Z line, numerous
      electron dense and polymorphic mitochondria, and deep infoldings of the plasma
      membrane. The hydroxyproline concentration was higher in the FR animals (p <
      0.01). FR prolonged the contraction and relaxation time of the papillary muscle
      and did not change its ability to contract and shorten. In conclusion, although a
      90-day period of FR caused striking myocardial ultrastructural alterations and
      increased the collagen concentration, it only minimally affected the mechanical
      function.

PMID- 11599776
TI  - Sarpogrelate diminishes changes in energy stores and ultrastructure of the
      ischemic-reperfused rat heart.
AB  - Although the involvement of serotonin in exacerbating vascular abnormalities in
      ischemic heart disease has been established, its role in mediating changes in
      cardiac function due to ischemia reperfusion (IR) is poorly understood. The aim
      of this study was to investigate the effect of a serotonin blocker, sarpogrelate
      (5-HT2A antagonist), in preventing cardiac injury due to IR. Isolated rat hearts
      were subjected to 30 min of global ischemia followed by 1 h of reperfusion.
      Sarpogrelate (50 nM-0.9 microM) was infused 10 min before ischemia as well as
      during the reperfusion period. The IR-induced changes in left ventricular
      developed pressure, left ventricular end diastolic pressure, rate of pressure
      development, and rate of pressure decay were attenuated (P < 0.05) with
      sarpogrelate treatment. Sarpogrelate also decreased the ultrastructural damage
      and improved the high energy phosphate level in the IR hearts (P < 0.05). This
      study provides evidence for the attenuation of IR-induced cardiac injury by 5
      HT2A receptor blockade and supports the view that serotonin may contribute to the
      deleterious effects of IR in the heart.

PMID- 11599777
TI  - Respiratory and metabolic effects of decreased osmolality in conscious rats.
AB  - We investigated the respiratory and metabolic effects of decreased osmolality,
      and the potential roles of angiotensin II (ANG II) and the subfornical organ
      (SFO) in mediating these effects, in conscious Sprague-Dawley (SD) rats. Gastric
      water loading was induced either by oral gavage or an externalized indwelling
      stomach tube (20 mL x kg(-1) distilled water at body temperature). Repeated
      measurements after oral gavage were obtained with and without water loading and
      with and without ANG II receptor block (saralasin, 1.3 microg x kg(-1) x min(-1)
      iv). At 15 min after water loading by oral gavage, ventilation (V, 1.14+/-0.08 L
      x kg(-1) x min(-1)) and tidal volume (10.7+/-0.6 mL x kg(-1)) were transiently
      higher (P < 0.05), at a time when plasma osmolality was decreased (-8+/-1 mOsm),
      compared with gavage tube alone (0.95+/-0.08 L x kg(-1) min(-1) and 9.1+/-0.7 mL
      x kg(-1), respectively). However, water loading via stomach tube did not
      stimulate V; only during the 60-s period of water infusion did V increase
      briefly, but this was due to increased respiratory frequency. Dye indicators
      demonstrated that oral gavage exposes upper airway and esophageal afferents to
      water, presumably accounting for respiratory stimulation. Lesions of the SFO did
      not affect respiration or metabolism. A decrease in osmolality, associated with
      both water loading techniques, caused a sustained increase in oxygen consumption
      (Vo2 ) and a decrease in the V/Vo2 ratio. ANG II receptor block reduced the Vo2
      response and prevented the decrease in V/Vo2 following water loading by oral
      gavage, but did not affect the transient stimulation of V. Unlike larger mammals,
      decreased osmolality does not stimulate respiration in the SD rat.

PMID- 11599778
TI  - Coexisting independent sodium-sensitive and sodium-insensitive mechanisms of
      genetic hypertension in spontaneously hypertensive rats (SHR).
AB  - Some essential hypertensive patients and genetic hypertensive rat strains have
      less than the normal levels of Mg2+ tightly bound to the plasma membranes of
      their erythrocytes and other cells, i.e., the magnesium binding defect (MgBD).
      This binding defect appears to cause increased passive permeability of the
      membrane to Na+ and thereby its increased intracellular concentration,
      particularly if the Na+-extrusion enzyme systems of the cell are also defective.
      The Na+-Ca2+ exchange system in the cell membrane exports Na+ and imports Ca2+,
      increasing the tone of the smooth muscle cell and thus producing hypertension
      (HTn). This HTn is Na+-sensitive. Evidence supporting this postulate was obtained
      by determining the intraerythrocyte total concentrations of Na+, Ca2+, K+, and
      Mg2+ in two strains of spontaneously hypertensive rats (SHR and SS/Jr rats,
      having the MgBD together with the other requisites of the Na+-sensitive pathway)
      and their respective controls (WKY and SR/Jr rats, in which this complete pathway
      is absent). The Na+ and Ca2+ concentrations in the hypertensive rats were
      increased, and that of K+ was decreased. The concentrations of these cations were
      very similar in the two hypertensive strains. The level of membrane tightly bound
      Ca2+ in SHR erythrocyte membranes was significantly higher than those in the
      other three rat strains, which were not statistically different from each other.
      These results support previously reported evidence of the existence of a novel
      HTn-generating mechanism in the SHR rat, in which the intracellular Ca2+
      concentration is increased as the result of the enhanced diffusion of this ion
      into the cell and the accompanying deficiency of the Ca2+ extrusion enzyme
      systems. This pathway is therefore Na+-insensitive, i.e., Ca2+-sensitive.

PMID- 11599779
TI  - Regulation of leukocyte adhesion to heart by the tripeptides feG and feG(NH2).
AB  - The role of the D-isomeric form of the salivary gland tripeptide FEG (feG) and
      its carboxyl-amidated derivative, feG(NH2), in regulating leukocyte adherence to
      nonfixed atrial slices from Sprague-Dawley rats was examined under static
      conditions. Optimal binding of the leukocytes was seen if the leukocytes were
      treated with platelet activating factor (PAF; 10(-9)M). The increased adherence
      of PAF-treated peripheral blood leukocytes was totally inhibited by both feG and
      feG(NH2) (10-9M), as well as by antibodies against CD18 and CD49d. In contrast,
      the binding of peritoneal leukocytes was blocked only by CD49d antibody.
      Circulating leukocytes obtained from lipopolysaccharide (LPS) treated (2 mg/kg
      ip) rats did not bind to atrial slices obtained from normal hearts, but readily
      bound to atrial slices obtained from LPS-treated rats. This leukocyte binding was
      inhibited by in vivo feG treatment (100 microg/kg ip, 24 h before harvest) or by
      treating the isolated cells with feG (10(-9)M). The amidated peptide feG(NH2)
      reduced neutrophil accumulation in the atrium elicited by ip injection of LPS,
      whereas feG was ineffective. The reduction in neutrophil infiltration into the
      myocardium by feG(NH2) and the prevention of leukocyte interaction with myocytes
      seen with both feG and feG(NH2) probably results in hindered leukocyte migration
      in the inflamed heart, resulting in less tissue damage. The inhibition by these
      tripeptides on neutrophil adhesion to myocytes suggests that salivary glands
      hormones regulate the severity of cardiac inflammation.

PMID- 11599780
TI  - Magnesium sulfate attenuates increased blood-brain barrier permeability during
      insulin-induced hypoglycemia in rats.
AB  - Magnesium probably protects brain tissue against the effects of cerebral
      ischemia, brain injury and stroke through its actions as a calcium antagonist and
      inhibitor of excitatory amino acids. The effects of magnesium sulfate on
      cerebrovascular permeability to a dye, Evans blue, were studied during insulin
      induced hypoglycemia with hypothermia in rats. Hypoglycemia was induced by an
      intramuscular injection of insulin. After giving insulin, each animal received
      MgSO4 (270 mg/kg) ip, followed by a 27 mg/kg dose every 20 min for 2.5 h. Plasma
      glucose and Mg2+ levels of animals were measured. Magnesium concentrations
      increased in the serum following MgSO4 administration (6.05+/-0.57 vs. 2.58+/
      0.14 mg/dL in the Mg2+ group, and 7.14+/-0.42 vs. 2.78+/-0.06 mg/dL in the
      insulin + Mg2+ group, P < 0.01). Plasma glucose levels decreased following
      hypoglycemia (4+/-0.66 vs. 118+/-2.23 mg/dL in the insulin group, and 7+/-1.59
      vs. 118+/-4.84 mg/dL in the insulin + Mg2+ group, P < 0.01). Blood-brain barrier
      permeability to Evans blue considerably increased in hypoglycemic rats (P <
      0.01). In contrast, blood-brain barrier permeability to Evans blue was
      significantly reduced in treatment of hypoglycemic rats with MgSO4 (P < 0.01).
      These results indicate that Mg2+ greatly reduced the passage of exogenous
      vascular tracer bound to albumin into the brain during hypoglycemia with
      hypothermia. Mg2+ could have protective effects on blood-brain barrier
      permeability against insulin-induced hypoglycemia.

PMID- 11599781
TI  - The in vivo toxicity of carbon tetrachloride and carrageenan on heart microsomes:
      analysis by Fourier transform infrared spectroscopy.
AB  - We investigated the sensitivity of rat heart microsomes to free radical attack
      using Fourier transform infrared (FT-IR) spectroscopy. This physico-chemical
      method seemed a valuable technique: quite sensitive to changes in the vibrational
      spectra. The spectral variations observed between normal and treated rats were in
      great part due to reactive oxygen species that led to changes in protein
      conformation involving beta-sheets, aggregation of proteins, and modification of
      protein synthesis. Carrageenan-induced inflammation slightly enhanced the total
      lipid content; rearrangement of acyl chains and accumulation of cholesterol
      esters and phospholipids also occurred in the treated rats. Carbon tetrachloride
      induced a decrease in both lipid and protein contents. The level of glucidic
      substrates was diminished with carbon tetrachloride and enhanced with
      carrageenan; these changes were due to metabolic interactions between cell
      components and drugs. FT-IR spectroscopy provided an accurate means to monitor,
      in rat heart, the in vivo effects of inflammatory and peroxidative damages, to
      discriminate and classify the affected cells, and to correlate the findings with
      known physiological and biochemical data in close relationship with metabolic
      disruptions induced by the two xenobiotics.

PMID- 11599782
TI  - Characterization of the mechanisms involved in the gender differences in p
      aminohippurate renal elimination in rats.
AB  - Gender differences in the renal handling on drugs and toxins have received too
      little attention. In the present study, a variety of preparations were used to
      examine the basis for the greater effectiveness of the male kidneys in the
      elimination of p-aminohippurate (PAH) in rats. Renal clearance of PAH was
      significantly lower in female rats as consequence of its smaller filtered and
      secreted load. The gender difference in the filtered load may be accounted for
      the lower value of glomerular filtration rate (GFR) displayed by female rats as
      compared with males. The lower value of the renal blood flow observed in females
      might explain, at least in part, the decrease in the GFR and in the secreted load
      of PAH. In females, maximal uptake for PAH transport into renal basolateral
      membrane vesicles decreased to 52+/-9% (P < 0.05) and Michaelis-Menten constant
      for PAH uptake into renal brush border membrane vesicles was increased to 163+/
      8% (P < 0.05). These changes might also explain the lower secreted load of PAH.
      The sex difference in the renal clearance of PAH was also evidenced by the
      reduced systemic clearance observed in female rats.

PMID- 11599783
TI  - Isolation of regioisomers of N-alkylprotoporphyrin IX from chick embryo liver
      after treatment with porphyrinogenic xenobiotics.
AB  - Several porphyrinogenic xenobiotics cause mechanism-based inactivation of
      cytochrome P450 (P450) isozymes with concomitant formation of a mixture of four N
      alkylprotoporphyrin IX (N-alkylPP) regioisomers, which have ferrochelatase
      inhibitory properties. To isolate the four regioisomers of N-methylprotoporphyrin
      IX (N-methylPP), 3,5-diethoxycarbonyl, 1-4-dihydro-2,4,6-trimethylpyridine (DDC)
      was administered to untreated, beta-naphthoflavone-, phenobarbital-, and
      glutethimide-pretreated 18-day-old chick embryos. Separation of the N-methylPP
      regioisomers by high pressure liquid chromatography (HPLC) revealed no marked
      difference in the regioisomer pattern among the different treatments. After
      administration of griseofulvin, allylisopropylacetamide (AIA), or 1-[4-(3-acetyl
      2,4,6-triemethylphenyl)-2,6-cyclohexanedionyl]-O-ethyl propionaldehyde oxime
      (ATMP) to untreated and glutethimide-pretreated 18-day-old chick embryos, an N
      alkylPP was isolated after AIA administration only. This finding strengthened
      previous reports of the species specificity of N-alkylPP formation with
      griseofulvin and ATMP. A series of dihydropyridines, namely 4-ethylDDC, 4
      hexylDDC, and 4-isobutylDDC were administered to untreated and glutethimide
      pretreated 18-day-old chick embryos and hepatic N-alkylPPs were isolated and
      separated by HPLC into regioisomers. The regioisomer patterns obtained did not
      support a previous proposal of masked regions above both rings B and C in the
      heme moieties of the P450 isozymes responsible for N-alkylPP formation. However,
      the data support the hypothesis of a partially masked region above ring B alone.
      The regioisomer patterns were in agreement with results previously obtained in
      rats showing that the percentage of Nc and (or) ND regioisomers in the
      regioisomer mixture increases as the length and bulk of the 4-alkyl substituent
      of a DDC analogue increase. Differences in the regioselectivity of heme N
      alkylation may be due to intrinsic chemical features of DDC analogues themselves
      or to differences in the P450 isozymes inactivated.

PMID- 11599784
TI  - Transport energetics of the Na+ pump in Aplysia californica gut.
AB  - Basolateral membranes of Aplysia californica foregut epithelia contain an ATP
      dependent Na+ transporter (Na+ pump). Increased activity of the Na+ pump, coupled
      to luminal Na+/AIB symporter activity and basolateral membrane depolarization,
      changed the Na+ transport energetics across the basolateral membrane to a greater
      extent than the change in Na+ transport energetics across the luminal membrane.

PMID- 11599785
TI  - Cardiorespiratory effects of prolonged angiotensin II block in resting conscious
      dogs.
AB  - Intravenous (iv) infusion of the angiotensin II (ANG II) receptor blocker
      saralasin in resting conscious dogs during physiological pertubations, such as
      hypotension and prolonged hypoxia, indicates the presence of an ANG II drive to
      increase respiration and decrease the arterial partial pressure of CO2 (PaCO2).
      In contrast, in eupneic resting dogs on a regular chow diet, iv infusion of
      saralasin for short periods (up to 30 min) provides no evidence of a tonic effect
      of circulating levels of ANG II on acid-base balance, respiration, metabolism, or
      circulation. However, ANG II influences physiological processes involving salt,
      water, and acid-base balances, which are potentially expressed beyond a 30 min
      time period, and could secondarily affect respiration. Therefore, we tested the
      hypothesis that blocking ANG II with iv saralasin would affect respiration and
      circulation over a 4-h period. Contrary to the hypothesis, iv infusion of
      saralasin in resting conscious eupneic dogs on a regular chow diet over a 4-h
      period had no effects on plasma strong ions, osmolality, acid-base balance,
      respiration, metabolism, or circulation when compared with similar control
      studies in the same animals. Thus, ANG II does not play a tonic modulatory role
      in respiratory control under "normal" physiological conditions.

PMID- 11599786
TI  - Space Life Sciences Planning Workshop.

PMID- 11599787
TI  - Natural antibodies to nematode biotinyl-enzymes in human sera.
AB  - Biotinyl-enzymes are conservative molecules present in helminths, as well as in
      other animals, bacteria and plants. They have recently been found to be antigenic
      in mice, and a potential source of cross-reactivity among helminths. This study
      investigated the presence in human sera of antibodies reactive with biotinyl
      enzymes from the nematodes Anisakis simplex, Toxocara canis and Ascaris suum.
      Biotinyl-enzymes from all these nematodes were recognized by IgG1 antibodies in
      sera from healthy subjects and from Anisakis-free patients infected with other
      parasites. Interestingly, IgE antibodies reactive with Anisakis simplex biotinyl
      enzymes were present in about one third of the sera from Anisakis-free patients
      infected with other parasites. Our results also demonstrate that the anti-BE IgG1
      and IgE antibodies present in the sera of Anisakis-free subjects are cross
      reactive among helminths. We conclude that biotinyl-enzymes from nematodes are
      recognized by natural human antibodies, although Anisakis biotinyl-enzymes do not
      seem to be the cause of sensitization. Since sera from the Anisakis-free
      population also present these antibodies, as-yet unidentified factors (dietary
      components, intestinal inflammation and/or the presence of parasites) may
      contribute to the induction of anti-BE antibody background.

PMID- 11599788
TI  - Contrasting responses of human gingival and colonic epithelial cells to
      lipopolysaccharides, lipoteichoic acids and peptidoglycans in the presence of
      soluble CD14.
AB  - Gingival epithelial cells may form the first barriers of defense against oral
      bacteria in periodontal tissues. We stimulated human gingival epithelial cells
      (keratinocytes) in primary culture, the oral epithelial cell line KB and the
      colonic epithelial cell line SW620 with various bacterial cell-surface components
      in the presence or absence of soluble CD14 (sCD14). The SW620 produced interlukin
      8 (IL-8) in an sCD14-dependent manner in response to lipopolysaccharide,
      lipoteichoic acid and peptidoglycan. However, the primary gingival epithelial
      cells and KB cells did not show enhanced production of IL-8 upon stimulation with
      these components even in the presence of serum. These human epithelial cells were
      devoid of membrane CD14, as determined by flow cytometry, and CD14 mRNA
      expression, as determined by reverse transcriptase-PCR. In contrast, gingival
      epithelial cells and KB cells expressed the mRNA expression for Toll-like
      receptor (TLR) 2, TLR4, MD2 and MyD88 to the similar extent to those observed in
      SW620 cells.

PMID- 11599789
TI  - Characterization of the cellular and humoral immune response to outer surface
      protein C and outer surface protein 17 in children with early disseminated Lyme
      borreliosis.
AB  - OspC and Osp17 are immunodominant proteins of Borrelia burgdorferi eliciting a
      clear humoral immune response in adult patients with systemic Lyme disease. In
      this study, the cellular immune response to B. burgdorferi and the major outer
      surface proteins OspC and Osp17 was investigated in children during the course of
      early disseminated B. burgdorferi infection. Lymphoproliferative responses to
      recombinant proteins were compared to the protein-specific humoral immune
      reaction. OspC induced a clear antibody response but elicited an even stronger
      cellular immune response. In contrast, a cellular as well as humoral immune
      reaction to Osp17 was only rarely detected. Follow-up examinations demonstrated
      that the lymphoproliferative response to B. burgdorferi and OspC persisted for
      several months after antibiotic therapy. Here, we show that in early disseminated
      Lyme disease of childhood, OspC is a potent antigen influencing both the humoral
      and cellular immunity, while Osp17 plays only a minor role in immune activation.

PMID- 11599790
TI  - Herpes simplex virus type 2 modulates the susceptibility of human bladder cells
      to uropathogenic bacteria.
AB  - The present study analyses the susceptibility of human bladder-derived cells (HT
      1376) to the infection by herpes simplex virus type 2 (HSV-2) and Chlamydia
      trachomatis, as well as to the adhesiveness of uropathogenic bacteria. HT-1376
      cells were efficiently infected by HSV-2 strain 333, as demonstrated by
      immunofluorescence staining of viral antigens, titration of cytopathic effect,
      and visualisation by transmission electron microscopy. This cell model was also
      prone to C. trachomatis (serovar E, Bour strain) replication and to the adherence
      of clinical uropathogenic isolates of Escherichia coli, Pseudomonas aeruginosa,
      Proteus vulgaris and Enterococcus faecalis. The pre-infection of HT-1376 cells
      with HSV-2 caused a tenfold increased adherence of an E. coli strain (U1),
      isolated from a patient affected by severe haemorrhagic cystitis, whereas in HSV
      2 pre-infected cells the number of C. trachomatis inclusion bodies was
      significantly reduced. Our findings indicate that these cells are a suitable in
      vitro model for studying infection and super-infection of the lower urinary tract
      by viruses and bacteria.

PMID- 11599791
TI  - Nramp1 gene affects selective early steps in macrophage-mediated anti
      cryptococcal defense.
AB  - Cryptococcus neoformans is an opportunistic fungus responsible for severe and
      often recurrent meningoencephalitis in immunodepressed patients. Initial evidence
      suggests that C. neoformans is a facultative intracellular pathogen; however, the
      strategies by which C. neoformans undergoes survival and eventually proliferation
      have not been elucidated. We investigated the role of Nrampl gene in macrophage
      mediated anti-cryptococcal defense. Using cell lines expressing the functional,
      mutated or knockout gene, it was established that Nramp1 (1) is not involved in
      the phagocytic event, (2) influences anti-cryptococcal activity in the early
      steps but not at later times, and (3) is unrelated to the biomolecular pathways
      through which C. neoformans impairs macrophage secretory response. Although the
      functional role of Nramp1 is still far from being elucidated, the present data
      add insight into its involvement in macrophage-mediated antimicrobial defense,
      particularly in the initial steps allowing C. neoformans growth inhibition.

PMID- 11599792
TI  - Interaction of Staphylococcus epidermidis with endothelial cells in vitro.
AB  - Staphylococcus epidermidis is a leading cause of nosocomial bacteremia, yet
      virtually nothing is known about how this pathogen interacts with human
      endothelial cells. We present evidence here that two biofilm-producing strains of
      S. epidermidis adhere to two types of endothelial cell lines in vitro and that
      adherence is significantly increased after briefly heat-treating the bacteria at
      40 degrees C in the presence of calcium. This mild heat treatment resulted in
      bacteria that were 5 to more than 20 times more adherent than untreated controls.
      While the adherence of bacteria in all phases of growth was increased after heat
      treatment, heat-treated late stationary phase cells were generally the most
      adherent. Electron microscopy demonstrated that S. epidermidis was internalized
      and appeared to exist free in the cytoplasm. Adherence to endothelium, should it
      occur in vivo during bacteremia, may be a virulence factor associated with this
      bacterium's pathogenesis.

PMID- 11599793
TI  - Antibodies to Lassa virus Z protein and nucleoprotein co-occur in human sera from
      Lassa fever endemic regions.
AB  - It is not known whether the small 11-kDa Z protein of Lassa virus is immunogenic
      during human Lassa virus infection. To obtain evidence for the existence of an
      antibody response and to test the suitability of these antibodies for
      serosurveys, sera from Lassa fever endemic regions (Guinea and Nigeria, n = 75)
      were tested for co-reactivity to Z protein and nucleoprotein (NP). Sera from a
      non-endemic region (Uganda, n = 50) served as a specificity control. Z protein
      and NP were expressed in Escherichia coli, affinity-purified, and used as antigen
      in Western blot. Indirect immunofluorescence (IIF) with Lassa virus-infected
      cells was performed for comparison. Due to high unspecific reactivity of the
      African sera, Western blot testing was performed with a 1:1,000 serum dilution.
      Under these conditions, none of the control sera but 12% of the sera from endemic
      regions co-reacted with both Z protein and NP. Reactivity to Z protein was
      significantly associated with NP reactivity (P < 10(-6)). NP and Z protein
      specific antibodies were co-detected in 33% of the IIF-positive sera and in 5% of
      the IIF-negative sera (P = 0.001). These data provide evidence for appearance of
      antibodies to Z protein and NP following Lassa virus infection. A recombinant
      blot for detection of both antibody specificities seems to be specific but less
      sensitive than IIF.

PMID- 11599794
TI  - Butylhydroxytoluene (BHT) increases susceptibility of transgenic rasH2 mice to
      lung carcinogenesis.
AB  - PURPOSE: Transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice)
      are highly susceptible to lung carcinogens. In order to investigate the
      possibility of developing a rapid in vivo assay for lung carcinogens, we examined
      whether the tumor-promoting activity of butylhydroxytoluene (BHT) is efficacious
      in rasH2 mice. METHODS: rasH2 mice and wild littermates of both genders were pre
      treated with carcinogens [urethane (UR), 4-nitroquinoline 1-oxide (4NQO) or
      diethylnitrosamine (DEN)], and, one day later, given a 400 mg/kg dose of BHT.
      RESULTS: Six weeks after the initiation treatment, evidence of carcinogenicity
      could be detected in male and female rasH2 mice that had received UR doses of >
      or = 250 mg/kg and > or = 125 mg/kg, respectively, prior to exposure to BHT,
      whereas only 500 mg/kg of UR was sufficient to induce tumors in female rasH2 mice
      given the carcinogen alone. The carcinogenicity of 15 mg/kg of 4NQO could be
      detected after 9 weeks in male rasH2 mice given the carcinogen followed by BHT.
      Similarly, the carcinogenicity of 60 mg/kg of DEN could be detected after 9 weeks
      and 6 weeks, respectively, in male and female rasH2 mice given the carcinogen
      followed by BHT. No carcinogenicity could be demonstrated through the
      experimental period with doses of 4NQO or DEN given alone. CONCLUSIONS: These
      results indicate that BHT administration increases the susceptibility of rasH2
      mice to lung carcinogens, and suggest that the use of BHT in rasH2 mice might
      lead to the establishment of a rapid in vivo assay for lung carcinogens.

PMID- 11599795
TI  - Cell type-specific induction of O6-alkylguanine-DNA alkyltransferase mRNA
      expression in rat liver during regeneration, inflammation and preneoplasia.
AB  - PURPOSE AND METHODS: To investigate the potential role of an aberrant cellular
      DNA repair in target cells during malignant transformation we studied cell type
      specific mRNA expression of the DNA repair protein O6-alkylguanine-DNA
      alkyltransferase (O6-AGT) in normal and regenerating rat liver, chronic hepatitis
      and preneoplastic liver lesions by in situ hybridization and semiautomatic image
      analysis. RESULTS: O6-AGT mRNA expression was found to be four to five times
      higher in hepatocytes than in nonparenchymal cells. A 1.9-fold increase in O6-AGT
      mRNA was observed after partial hepatectomy. Intraperitoneal injection of
      diethylnitrosamine led to a 1.3-fold and 2.6-fold rise in periportal and
      perivenous hepatocytes, respectively. Ethylnitrosourea produced an enhancement of
      mRNA levels up to 1.6-fold in hepatocytes without regional differences. In
      megalocytic hepatocytes of Long-Evans Cinnamon rats with chronic hepatitis, a 4.4
      fold mRNA induction was found. In small preneoplastic lesions induced after
      chronic diethylnitrosamine-exposure, O6-AGT mRNA expression was identical to that
      of adjacent normal tissue. Intermediate and large lesions revealed 1.5- to 1.6
      fold higher mRNA levels. CONCLUSIONS: These results suggest an induction of O6
      AGT mRNA expression in hepatocellular target tissue under conditions of increased
      carcinogen sensitivity . The O6-AGT expression in early preneoplastic lesions did
      not differ from normal surrounding liver tissue, thus excluding the possibility
      that progression of preneoplasia in rat liver is associated with a deficient mRNA
      expression of this DNA repair protein. On the contrary, enhanced O6-AGT mRNA
      expression in more advanced foci and early neoplastic nodules may confer a
      selective advantage upon early malignant hepatocytes with regard to further tumor
      progression.

PMID- 11599796
TI  - Esophageal squamous cell carcinomas with DNA replication errors (RER+) are
      associated with p16/pRb loss and wild-type p53.
AB  - PURPOSE: Microsatellite instability (MSI) as a determinant of propensity to
      esophageal squamous cell carcinoma (ESCC) at seven microsatellite markers at 2p
      (2p15-16), 3p (3p13, 3p14.1-3, 3p25, and 3p26) and 16q (16q12.1-3) was
      investigated to analyze their putative role as indicators of predisposition to
      esophageal malignancies. METHODS: Seven microsatellite loci were amplified by
      polymerase chain reaction, from surgically resected tumor tissues from 30 ESCC
      patients from Indian population, to assess the loss of heterozygosity (LOH) and
      replication error repeats (RER) and to correlate these alterations with
      aberrations in major cell cycle regulatory proteins and histopathological
      parameters. RESULTS: LOH and RER analyses at these loci demonstrated moderate
      microsatellite alterations, suggesting the involvement of MSI in esophageal
      tumorigenesis in a subset of the Indian population. MSI, defined as RER in at
      least two or more of the loci studied, was observed in ten of 30 (33%) patients.
      Twenty-two of 30 patients (73%) showed LOH at one or more loci, while 17 of the
      30 patients (60%) showed RER in at least one of the loci studied. RER-positive
      patients showed a trend towards better prognosis when compared to RER-negative
      patients. MSI demonstrated a significant association with concomitant loss of p16
      and pRb (p16-/pRb- phenotype) (P=0.046). Interestingly, we observed an inverse
      correlation between MSI and p53 mutations (P=0.03) suggesting that MSI may
      provide a p53-independent pathway for esophageal tumorigenesis in RER+ patients.
      MSI showed a trend towards longer survival and absence of distant organ
      metastasis (P=0.06). CONCLUSIONS: The present study demonstrates the probable
      role of MSI in esophageal squamous cell carcinoma in the Indian population.
      Instability associated with the repetitive sequences--the revealing marks of loss
      of DNA replication fidelity may serve as an indicator of predisposition to
      esophageal cancer.

PMID- 11599797
TI  - Isolation and characterization of a novel cDNA, UBAP1, derived from the tumor
      suppressor locus in human chromosome 9p21-22.
AB  - PURPOSE: To clone the putative tumor suppressor gene(s) in a refined region at
      9p21-22 undergoing loss of heterozygosity in nasopharyngeal carcinoma (NPC).
      METHODS: We systematically screened the expression patterns of 25 novel ESTs
      (expressed sequence tags) in a minimal common deleted region of 9p21-22 in NPC.
      One of these ESTs was found down-regulated in NPC. Subsequently, the
      corresponding gene sequence of this EST was established by cDNA cloning and RACE
      (rapid amplification of cDNA end) procedures. Furthermore, a mouse homologue of
      this gene was identified. The expression of this gene was examined using Northern
      blot or reverse transcription-polymerase chain reaction (RT-PCR) in various human
      and mouse tissues. A limited screen for mutation of coding sequence of this novel
      human gene was undertaken using RT-PCR and direct sequencing analysis. RESULTS: A
      novel gene was cloned. This gene is a new member of the UBA domain family, so we
      named it UBAPI for ubiquitin-associated protein 1 (HUGO Gene Nomenclature
      Committee-approved symbol). Northern blot and RT-PCR analysis demonstrate a
      ubiquitous pattern of gene expression in human and mouse tissues. The direct
      sequencing analysis of the coding region of hUBAP1 following RT-PCR failed to
      reveal any mutations in a preliminary screen of NPC cell line HNE1 and primary
      nasopharyngeal carcinoma samples. CONCLUSIONS: We cloned a novel gene UBAPI,
      which is highly conserved between human and mouse. Clearly, as a novel member of
      UBA domain protein family and taking its map location into account, a more
      extensive analysis is essential to establish whether subtle mutations are present
      in nasopharyngeal carcinomas.

PMID- 11599798
TI  - GM-CSF safety and effects in the management of advanced/refractory multiple
      myeloma patients: a phase I trial.
AB  - PURPOSE: Some limitations of effective therapy in multiple myeloma include the
      low growth fraction of the malignant plasma cells, multi-drug resistance, and the
      presence of other concurrent diseases in this patient population. A phase I study
      was conducted to evaluate the toxicity of granulocyte macrophage colony
      stimulating factor (GM-CSF) in myeloma patients as well as the potential effect
      on the plasma cell labeling index (PCLI). Relapsed patients with multiple myeloma
      were eligible. METHODS: The first phase of this trial assessed the toxicity
      (including the effect on disease progression) of escalating doses (125-500
      microg/m2 SC, days 1-5) of GM-CSF, and the effects of this cytokine on PCLI.
      Patients whose PCLI doubled and increased to > or = 1.7% were treated with
      chemotherapy including cyclophosphamide, vincristine, prednisone, and GM-CSF.
      Twenty-two patients were enrolled. RESULTS: The toxicity of GM-CSF was mild, and
      no dose-limiting side effects were seen. Twenty-five percent of patients (5/20)
      achieved the target PCLI, and 4/5 proceeded to receive chemotherapy. No
      relationship of GM-CSF dose to increases of the PCLI was noted. All patients who
      received chemotherapy responded. CONCLUSIONS: GM-CSF has acceptable toxicity in
      patients with multiple myeloma and produced increases of PCLI in selected
      individuals. Further studies of GM-CSF alone or in combination with chemotherapy
      are indicated.

PMID- 11599799
TI  - Inhibition of endothelial cell proliferation and tumor-induced angiogenesis by
      pentoxifylline.
AB  - PURPOSE: In this study we investigated the effect of pentoxifylline (PTX) on
      tumor-induced neovascularization as well as on different steps involved in the
      angiogenic process. METHODS: To assess angiogenesis inhibition. we injected
      intradermally (i.d.) 10 B16-F10 melanoma cells into C57BL/6J mice which were
      subsequently intraperitoneally (i.p.) inoculated with PTX or saline. On day 7 the
      number of blood vessels converging to the remnant of injected material was
      counted and the volumes of incipient tumors were calculated in each case. In
      vitro growth inhibition by PTX was evaluated in two different cell lines of
      endothelial origin and in human umbilical vein endothelial cells. Motility
      assays, as well as zymographic assays carried out to analyze gelatinolytic
      metalloproteinases and urokinase-type plasminogen activator, were performed in
      one of the endothelial cell lines. RESULTS: A significant inhibition of tumor
      induced angiogenesis was observed in C57B1/6 mice i.p. inoculated with PTX, that
      paralleled reduced incipient tumor volumes. The endothelial cells derived from
      different sources were inhibited in a dose-response manner by PTX in vitro. Non
      cytotoxic PTX concentrations assayed in one of the endothelial cell lines did not
      inhibit its in vitro cell motility nor its gelatinase secretion, but its low
      molecular weight urokinase-type plasminogen activator expression. CONCLUSIONS:
      Our findings suggest that the inhibitory effect of PTX on tumor angiogenesis is
      related to antiproliferative action on endothelial cells, as well as to down
      regulation of u-PA secreted by them.

PMID- 11599800
TI  - Serum matrix metalloproteinase-2 in patients with malignant melanoma.
AB  - PURPOSE: Matrix metalloproteinases (MMPs) are a family of structurally related
      zinc-dependent endopeptidases that are able to degrade extracellular matrix
      components. MMPs play a role in tumor invasion and tumor metastasis. MMP-2 (also
      known as gelatinase A) is expressed in human melanoma cells. METHODS: In this
      study, we measured MMP-2 in 337 serum probes of 166 melanoma patients with a
      recently developed enzyme immunoassay and compared these data with the tumor
      stage, presence of metastases, and the levels of S100beta and soluble
      intracellular adhesion molecule-1 (sICAM-1) in serum. RESULTS: The mean levels
      were (189.2 +/- 50.8) ng/ml for MMP-2, (263.2 +/- 74.1) ng/ml for sICAM-1, and
      (0.424 +/- 1.568) U/ml for S100beta. There was a statistical significant
      correlation of MMP-2 with sICAM-1 (P=0.05) and Sl00beta (P=0.01). The mean MMP-2
      levels (in ng/ml) in patients with metastatic melanoma were 196.4 +/- 54.0 versus
      182.6 +/- 46.9 in non-metastasizing melanoma (P=0.037). However, there was no
      significant difference in MMP-2 levels between the different tumor stages.
      CONCLUSION: Determination of MMP-2 serum levels is of limited value as a tumor
      marker in melanoma, though there are higher levels in the more advanced disease.

PMID- 11599801
TI  - The Mumbai Conference on Molecular Targets in Cancer Cells: new paradigms in
      research and treatment.

PMID- 11599802
TI  - Bid to defer top-level plan to ban dog docking.

PMID- 11599803
TI  - AAHL is leading the world on paramyxoviridae research. Australian Animal Health
      Laboratory.

PMID- 11599804
TI  - AVA's UK FMD scheme gives worthwhile results for Australia.

PMID- 11599805
TI  - Vet pathology coming close to extinction.

PMID- 11599806
TI  - Vet figures reveal chronic shortage.

PMID- 11599807
TI  - Australia's responses to the UK FMD crisis.

PMID- 11599808
TI  - The crisis in vet education. Problems confronting Australia's veterinary schools.

PMID- 11599810
TI  - The crisis in vet education.

PMID- 11599809
TI  - Ill-advised proposal to ban certain dog breeds.

PMID- 11599811
TI  - Advice from the Veterinary Surgeons Board on an ethical issue.

PMID- 11599812
TI  - Peritonitis associated with Actinobacillus equuli in horses: 51 cases.
AB  - OBJECTIVE: To review the clinical findings, diagnosis and treatment of 51 horses
      with peritonitis attributed to Actinobacillus equuli. DESIGN: Retrospective study
      of clinical cases. METHODS: Breed, age and gender of horse, history, physical
      examination findings, treatment and outcome were determined from the hospital
      records of 51 horses in which a diagnosis of peritonitis attributed to A. equuli
      was made between January 1993 and June 1999. Results of abdominal fluid cytology
      and bacteriology, antimicrobial sensitivity patterns, haematology and faecal egg
      counts, when performed, were also retrieved. RESULTS: There was a variety of
      breeds of horses affected. There were 35 male and 17 female horses, aged from 9
      months to 22 years, presented. Lethargy, signs of depression with mild to
      moderate signs of abdominal pain and inappetence were the most common reasons for
      presentation. Most horses had elevated heart and respiratory rates, an elevated
      rectal temperature and reduced intestinal borborygmi heard on auscultation of the
      abdomen. Abnormal colour with an elevated protein were features of an abdominal
      fluid sample in 98% of horses and a marked elevation in nucleated cell count was
      present in all samples. Pleomorphic gram-negative rods were seen on cytology in
      53% of samples and a positive culture of A. equuli was returned in 72% of
      samples. Other laboratory findings in some horses included mild
      haemoconcentration, hypoproteinaemia, an elevated circulating nucleated cell
      count with a left shift, an elevation in fibrinogen concentration and an elevated
      faecal egg count. All horses demonstrated a rapid response to treatment with
      procaine penicillin alone, or a combination of procaine penicillin and gentamicin
      sulphate. Where antimicrobial sensitivity tests were performed, all but two
      isolates were sensitive to procaine penicillin. All horses responded to
      antimicrobial and supportive therapy and were discharged from hospital.
      CONCLUSION: Horses with A. equuli peritonitis present with similar clinical signs
      as horses with other causes of abdominal pain. However, these signs, when
      evaluated in conjunction with the results of abdominal fluid analysis and
      response to treatment, are characteristic of A. equuli peritonitis. Pleomorphic
      gram-negative bacteria may be seen on a cytological preparation of the abdominal
      fluid sample, and a positive bacterial culture may be obtained in some, but not
      all, cases. Most isolates are sensitive to procaine penicillin, so treatment with
      procaine penicillin and gentamicin sulphate is recommended until antimicrobial
      sensitivity is known.

PMID- 11599814
TI  - Effect of gender on ownership and income in veterinary practice.
AB  - OBJECTIVE: To estimate the effect of gender on ownership and income in veterinary
      practice in Australia. METHODS: Questionnaire completed by private veterinary
      practitioners, and analysed using the SAS System for Windows 7.0. RESULTS: More
      than three-quarters (78%) of male but 36% of female private practitioners were
      partial or sole owners of practices. The median annual income for all male
      practitioners working more than 40 hours/week was $70K, but that for females was
      $43K. These disparities existed in both city and country practices, and in the
      case of income it increased with increasing time in the workforce. Male practice
      owners also reported higher incomes than female owners. CONCLUSIONS: Female
      veterinary practitioners are less likely to own practices, and more likely to
      earn low incomes than males. These differentials do not appear to be due to
      location, hours worked or years since graduation or, in the case of income, to
      whether they are owners or employees. The evidence points to a lower interest by
      women than men in the business aspects of veterinary practice.

PMID- 11599813
TI  - Feline immunodeficiency virus status of Australian cats with lymphosarcoma.
AB  - OBJECTIVE: To determine the FIV status of Australian cats with lymphosarcoma and
      relate this to patient characteristics, tumour characteristics (tissue
      involvement, histological grade and immunophenotype), haematological and serum
      biochemical values and FeLV status of affected cats. DESIGN: Prospective study of
      101 client-owned cats with naturally-occurring lymphosarcoma. PROCEDURE: Western
      blot analysis, ELISA and immunochromatography were used to detect FIV antibodies
      in serum from cats with lymphosarcoma. RESULTS: On the basis of Western blot
      analysis (which was considered the most accurate method for determining FIV
      status), 50/101 (50%) of cats with naturally-occurring lymphosarcoma were
      positive for FIV antibodies. Of these 50 cats, 35 had tumours of B-cell
      phenotype, 13 had T-cell tumours and 2 had tumours classified as non-B/non-T.
      Tumours from eight of these FIV-positive cats contained FeLV gene sequences,
      including a 9-month-old cat with FeLV antigenaemia. Compared with FlV-negative
      cats with lymphosarcoma, FIV-positive cats were more likely to be domestic
      crossbreds (P = 0.004), male (P = 0.048) and have atypical (especially nasal)
      forms of lymphosarcoma (P = 0.09). Only 39 of 107 (36%) blood or sera tested
      using ELISA were positive for FIV antibodies (including 5 false-positives).
      CONCLUSIONS: The prevalence of FIV infection was considerably higher in our
      cohort of cats compared with series of lymphosarcoma cases from the Northern
      hemisphere. A positive FIV status was strongly associated with lymphosarcoma in
      Australian cats and it is possible that this infection may predispose to the
      development of lymphoid neoplasia. The presence of FIV infection would have been
      underestimated if commercial kits alone had been used for serology.

PMID- 11599815
TI  - Lateral canthoplasty for facial nerve paralysis and exposure keratitis in a
      mouse.
AB  - An 11-month old entire male mouse was presented with mucopurulent discharge and
      corneal scarring of the left eye. This mouse previously had a history of ear
      mites that responded to therapy, and had undergone surgery to remove a large
      discharging mass from the left side of the neck. The eye problem was noted prior
      to surgery, but after the ear mite infection. Examination revealed absence of a
      palpebral reflex in the left eye, and no spontaneous movements of the left ear or
      lip and whiskers. Examination of the left eye revealed extensive corneal
      vascularisation and pigmentation. Intraocular structures were not visible. A
      diagnosis of facial nerve paralysis and secondary exposure keratitis was made.
      Surgery was performed to close the lateral canthus and reduce corneal exposure.
      Following surgery the eye discharge ceased and corneal vascularisation resolved,
      however corneal pigmentation persisted.

PMID- 11599816
TI  - The first report of canine ehrlichiosis in Australia.

PMID- 11599817
TI  - Detection of Ehrlichia platys in dogs in Australia.
AB  - OBJECTIVE: To describe the detection of Ehrlichia platys in free-roaming dogs in
      Central Australia. PROCEDURE: Blood samples were collected from four dogs and
      examined for bacterial 16S ribosomal DNA using Polymerase Chain Reaction (PCR)
      based assays. The three positive samples obtained were then sequenced and
      identification of the PCR product carried out. As a result of all three samples
      being identical to or closely related to part of the 16S rRNA gene of E. platys,
      blood samples were subsequently obtained from a further 24 dogs. These samples
      were screened using a PCR-assay to determine the presence of Ehrlichia DNA using
      genus-specific primers. The positive samples obtained from the screening process
      were then subjected to a further PCR-assay using E. platys specific primers.
      RESULTS: Of 28 dogs sampled, Ehrlichia DNA was detected in the blood of 13 dogs.
      Sequencing of the amplicons obtained indicated a high homology with the 16S rRNA
      gene for E. platys. When the E. platys-specific PCR was performed for 10 of those
      dogs, the 678 bp product obtained from the PCR amplification confirmed the
      identification as part of the 16S rRNA gene of E. platys in all 10 dogs.
      CONCLUSION: This study reports for the first time Ehrlichia carriage by dogs in
      Australia. It also indicates the usefulness of the PCR technique in rapidly and
      accurately identifying diseases that are otherwise difficult to detect. By using
      universal primers directed against bacterial 16S ribosomal DNA and sequencing
      analysis, the detection of potentially pathogenic Ehrlichia organisms that had
      not previously been found in Australia has been made possible.

PMID- 11599818
TI  - Serological survey for Ehrlichia canis in urban dogs from the major population
      centres of northern Australia.
AB  - OBJECTIVE: To detect evidence of Ehrlichia canis infection of dogs from the major
      population centres of northern Australia, if present. DESIGN: Serological
      investigation for E. canis. PROCEDURE: The sera of 316 domestic dogs, collected
      from the northern Australian population centres of Townsville, Cairns, Darwin,
      Kununurra and Broome from May 1997 to August 1999, were investigated for evidence
      of infection with E. canis. Samples were tested for antibodies to E. canis using
      an indirect fluorescent antibody (IFA) test. The buffy coats from blood of dogs
      whose serum reacted in the IFA test were subsequently tested with a nested PCR to
      detect E. canis DNA. When available, blood from these dogs was injected into
      suckling mice, which were then examined for clinical disease and tested for the
      presence of E. canis antibodies. RESULTS: Of the 316 samples tested seven reacted
      in the IFA test for E. canis. None of the dogs from which these samples were
      obtained exhibited clinical signs of acute or chronic ehrlichiosis. The six
      positive samples available for testing were negative when tested with the nested
      PCR. Suckling mice inoculated with blood from three of the dogs whose serum was
      positive by IFA test showed no signs of clinical disease nor did their give
      positive reactions in the IFA test. CONCLUSIONS: No evidence of E. canis
      infection was confirmed in any of the dogs examined. Northern Australia would
      appear to remain free of this obligate parasite.

PMID- 11599819
TI  - Identification of equine herpesviruses 1 and 4 by polymerase chain reaction.
AB  - OBJECTIVE: To develop and validate specific, sensitive and rapid (< 8 hour)
      diagnostic tests using polymerase chain reaction (PCR) for the diagnosis of
      abortion and respiratory disease caused by equine herpesvirus 1 (EHV1; equine
      abortion virus) and EHV4 (equine rhinopneumonitis virus). DESIGN: Primer sets
      based on nucleotide sequences encoding glycoprotein H (gH) of EHV1 and gB of EHV4
      were designed and used in single round and second round (seminested) PCRs, and in
      a multiplex PCR for the diagnosis of EHV1 and EHV4 infections. METHODS:
      Oligonucleotide primers were designed for each virus, PCR conditions were defined
      and the specificity and sensitivity of the assays were determined. The tests were
      applied to tissue samples from aborted equine foetuses and to nasopharyngeal
      swabs from horses with acute febrile respiratory disease. RESULTS: Individual
      single round and a second round (seminested) EHV1 and EHV4 PCRs were specific in
      that EHV1 primers amplified all (n = 30) EHV1 isolates and did not amplify EHV4.
      Similarly EHV4 primers amplified all (n = 6) EHV4 isolates and did not amplify
      EHV1. Both PCRs were sensitive in that the first round EHV1 PCR detected 1220
      molecules of EHV1 plasmid DNA and the first round EHV4 PCR detected 7280
      molecules of EHV4 plasmid DNA. The EHV1 second round PCR was 100 times more
      sensitive in that it detected 12 molecules of EHV1 DNA and the EHV4 second round
      PCR was 1000 times more sensitive in that it detected 8 molecules of EHV4 DNA.
      There was a high correlation between detection of EHV1 by virus isolation and PCR
      when tissue samples from 71 aborted foetuses were examined; all samples positive
      by virus isolation were positive by PCR. Similarly the EHV4 PCR was at least as
      sensitive as virus isolation when applied to nasaopharyngeal swabs from horses
      with respiratory disease in that all samples positive by virus isolation were
      also positive by PCR. CONCLUSION: Individual single round and second round
      (seminested) PCRs and a seminested multiplex PCR were developed that enabled
      reliable, rapid detection of EHV1 and EHV4 in aborted foetal tissues and
      nasopharyngeal swab samples.

PMID- 11599820
TI  - Immune responses of teleost fish.
AB  - In fish all the pre-requisites to mount a specific immune response are present,
      but the main differences from the mammalian system are that the secondary
      response is relatively minor and IgG is not present. In teleosts mainly IgM is
      present, and IgD has been recently described but its function is, as yet,
      unknown. However, different forms of fish IgM and its observed flexibility of
      structure may compensate for a lack of Ig class diversity. The innate immune
      response of teleosts is highly developed. Multiple forms of key constitutive and
      inducible components, such as lysozyme, C3, alpha2-macroglobulin and C-reactive
      protein, are present, and may enhance immune recognition. Low ambient temperature
      appears to have an impact on all aspects of the immune response, particularly the
      T-dependent specific immune response due to the non-adaptive lipid composition of
      T-cell membranes. Temperature effects on the nonspecific immune system are less
      well characterised, but there is evidence that low temperatures are also
      suppressive. Knowledge of immune system function becomes essential for disease
      prevention strategies such as the development of vaccines, selection for
      increased disease resistance and identification of genes suitable for
      trangenesis.

PMID- 11599821
TI  - Postcardiac surgery mediastinitis mimicking acute inferior myocardial infarction.
AB  - Both inflammation and infarction may produce a similar clinical picture,
      including ST-segment elevation on the electrocardiogram. Typically, inflammation
      affects the whole myocardium, resulting in characteristic electrocardiographic
      changes in all epicardial leads. We describe a case of poststernotomy
      mediastinitis which produced electrocardiographic changes mimicking an acute
      inferior myocardial infarction.

PMID- 11599822
TI  - Swan-Ganz catheter entrapment in open heart surgery.
AB  - BACKGROUND AND AIM: Swan-Ganz catheterization is an important technique for
      monitoring perioperative and postoperative cardiac pressures during open heart
      surgery. However, although a rare condition, resistance may be encountered while
      removing the catheter postoperatively and its removal must be accomplished
      through surgery. METHODS: Between May 1988 and February 2000, we observed Swan
      Ganz catheter entrapment complications in 10 cases subjected to open heart
      surgery. All the cases had valve replacement. Five cases were male, while five
      were female. The Swan-Ganz catheter was retained in the vena cava cannulation
      suture in four cases, in the right atriotomy in three cases, in a left atriotomy
      suture in one case, and looped around the right ventricular papillary muscle in
      one case. In the last case, it was looped around chordae tendinea between the
      tricuspid valve conal papillary muscle and septal leaflet. Although
      cardiopulmonary bypass equipment was prepared, it was not utilized in any of the
      cases. The catheter was released and removed by placing a pursestring suture on
      the vena cava cannulation site in four cases, by placing a matrix suture on the
      proximal and distal part of the left or right atrial suture line and a purse
      string suture on the site of the entrapment in four cases, and by digital
      palpation from the right atrial appendage in two cases. RESULTS: All patients
      were taken to the intensive care unit postoperatively and to the wards the next
      day without complications. CONCLUSIONS: When performing open heart surgery, the
      surgeon should not leave the Swan-Ganz catheter in the suture while closing the
      right or left atriotomy or during venous cannulation. In addition, the catheter
      should be moved after suturing to ensure that there is no entrapment.

PMID- 11599823
TI  - Simplified Parsonnet risk scale identifies limits to early patient discharge.
AB  - BACKGROUND: Fast-track recovery after coronary artery bypass surgery has
      influenced patient care positively. Predicting patients who fall off track and
      require prolonged (> or =7 days) hospitalization remains uncertain. The Parsonnet
      risk assessment score is effective in predicting length of stay, but is limited
      by inaccurate subdivision of risk categories. We simplified the Parsonnet risk
      scale to better identify patients eligible for fast-track recovery. METHOD: The
      cases of 604 consecutive patients who underwent isolated coronary artery bypass
      grafting (CABG) using cardiopulmonary bypass (CPB) were reviewed retrospectively.
      A rapid recovery protocol emphasizing reduced CPB time, preoperative intra-aortic
      balloon pump (IABP) criteria, and atrial fibrillation prophylaxis was applied to
      all patients. The five original divisions of the Parsonnet risk scale were
      reduced to three risk categories: Low (0-10; Group A), Intermediate (11-20; Group
      B), High (> 20; Group C). Comparisons of progressive risk categories were
      analyzed to identify predictive factors associated with fast-track outcomes.
      RESULTS: The thirty-day operative mortality for the entire group was 3.6%. Three
      clinical features were identified that distinguished risk progression-female
      gender, reoperative CABG, and increased age. Additionally, the presence of
      diabetes (p < 0.05), congestive heart failure (p < 0.01), and peripheral vascular
      disease (p < 0.001) distinguished Groups A and B, while acute myocardial
      infarction (p < 0.05) influenced outcomes in Group C. Group A (48%) mean risk
      score 5.9+/-3.2 was compared to Group B (34%) 14.8+/-2.6, which was further
      compared to Group C (18%) 26.4+/-2.8. The mean length of stay for Group A (5.3+/
      4.1 days) was notably less than Group B (6.1+/-4.7 days; p < 0.05); however, both
      groups responded favorably to fast-track techniques. Group C did not respond
      comparably (9.2+/-9.2 vs 6.1+/-4.7 days; p < 0.001) and experienced prolonged
      recovery. The simplified Parsonnet risk scale did not identify differences in
      operative mortality and revealed only pneumonia (p < 0.05) and atrial
      fibrillation (p < 0.01) to be greater in Group C. As risk increased,
      significantly less revascularization was performed (Group A 3.6+/-1.2
      grafts/patient vs Group B 3.3+/-1.2 [p < 0.01]; Group B 3.3+/-1.2 vs Group C
      2.5+/-1.0 [p < 0.001]). CONCLUSION: A simplified Parsonnet risk scale (three
      categories) is an effective tool in identifying factors limiting fast-track
      recovery. Low- and intermediate-risk patients represent the majority (82%) and
      respond well to fast-track methods. High-risk patients (18%) are limited by a
      greater percentage of female patients, reoperative CABG, and the very elderly,
      resulting in fast-track failure. Strategies to improve recovery in high-risk
      patients may include evolving off-pump techniques.

PMID- 11599824
TI  - A comparison of steroid-eluting epicardial versus transvenous pacing leads in
      children.
AB  - OBJECTIVE: To evaluate the acute and chronic performance of steroid-eluting (SE)
      epicardial (EPI) pacing leads as compared to SE transvenous (TV) pacing leads in
      children. METHODS: From 1989 through 1997, 55 children with congenital heart
      disease received a total of 85 SE pacing leads, of which 38 were EPI and 47 TV.
      The mean age of children receiving EPI leads was younger than those receiving TV
      leads (7.7 months vs 15.1 years, p = 0.001), and they had shorter follow-up (17.2
      months vs 36.2 months, p < 0.001). All leads were evaluated for acute and chronic
      sensing and capture thresholds, and impedance. RESULTS: Acute and in particular
      chronic atrial and ventricular sensing and capture thresholds in SE EPI and TV
      leads were essentially equivalent. [table: see text]. The chronic impedance of TV
      leads (atrial 525 ohms, ventricular 520 ohms) was consistently higher than EPI
      leads (atrial 404 ohms, ventricular 386 ohms). CONCLUSION: At intermediate follow
      up, SE EPI leads are functionally equivalent to SE TV leads. We recommend the use
      of SE EPI leads as long as practically feasible prior to using the TV approach in
      children who will require a life-time of pacing.

PMID- 11599825
TI  - Simple sternal metal stent for delayed sternal closure.

PMID- 11599826
TI  - Ischemic preconditioning in myocardial revascularization with intermittent aortic
      cross-clamping.
AB  - BACKGROUND: This study tests the hypothesis that initial brief periods of
      ischemia can increase the protection obtained by intermittent aortic cross
      clamping. METHODS: In the control group (n = 18), the procedure was performed
      under intermittent aortic cross-clamping at 32 degrees C. Patients in the
      preconditioned gorup (n = 17) received a stimulus of two 3-minute periods of
      cross-clamping followed by 2 minutes of reperfusion prior to standard operation.
      CKMB, troponin 1, adenosine, and lactate were obtained from the great cardiac
      vein at the onset of cardiopulmonary bypass (CPB), at the end of the first
      anastomosis, and at the end of CPB. RESULTS: CKMB and troponin I were slightly
      higher at the end of CPB in the control group, while there was no difference
      between adenosine and lactate levels. [table: see text]. CONCLUSION: There was no
      difference between groups in terms of myocardial protection.

PMID- 11599827
TI  - Ultrastructural and immunohistochemical analysis of early myocardial changes
      following transmyocardial laser revascularization.
AB  - BACKGROUND AND AIM OF THE STUDY: Transmyocardial laser revascularization (TMR)
      has demonstrated significant relief in patients presenting with refractory
      angina. However, the mechanism by which TMR improves clinical symptoms is
      unclear. This study analyzes the early immunohistochemical and ultrastructural
      features of the human myocardium following TMR. METHODS: Specimens of myocardium
      that contained laser channels were removed in toto at autopsy from three male
      patients, ages 41, 57, and 65 (mean age 55.8) who had died 1 to 11 days (mean
      6.8) following laser revascularization. Consecutive parallel sections of
      specimens were stained with cell-type specific antibodies to CD3 (to identify T
      lymphocytes), CD68 (macrophages), Factor VIII (endothelial cells), and myosin
      (myocytes). Additionally, adjacent areas of myocardium that contained laser
      channels were processed and analyzed by transmission electron microscopy.
      RESULTS: The internal lining surface of laser channels was composed of vacuolized
      and condensed myocardial debris. No obvious connections were noted between laser
      channels and the ventricular cavity. No endothelialization of channels was
      observed, whereas the adjacent noninjured myocardium demonstrated microvessels
      lined by well-preserved endothelial cells. The laser channels were surrounded by
      zones of necrotic cardiomyocytes. CONCLUSIONS: Our observations suggest that
      laser channels are not lined by endothelial cells during the early stages
      following TMR. Mechanisms other than direct myocardial perfusion from the
      ventricular cavity by patent endothelialized channels may explain the immediate
      relief from angina provided by TMR.

PMID- 11599828
TI  - Low systemic vascular resistance after cardiopulmonary bypass: incidence,
      etiology, and clinical importance.
AB  - BACKGROUND: Low systemic vascular resistance during and immediately after cardiac
      surgery in which cardiopulmonary bypass is utilized is a well-known phenomenon,
      characterized as vasoplegia, which appears with an incidence ranging between 5%
      and 15%. The etiology is not completely elucidated and the clinical importance
      remains speculative. METHODS: In this prospective clinical trial, we assessed the
      incidence of postoperative low systemic vascular resistance in 800 consecutive
      patients undergoing elective coronary artery bypass grafting and/or valve
      replacement. We have attempted to identify the predictive factors responsible for
      the presence of low systemic vascular resistance and we have examined the
      subsequent postoperative outcome of those patients who developed early
      postoperative vasoplegia. The severity of vasoplegia was divided into three
      groups according either to the value of systemic resistance and/or the dose of
      vasoconstrictive agents necessary to correct the hemodynamic. RESULTS: Six
      hundred twenty-five patients (78.1%) did not develop vasoplegia, 115 patients
      (14.4%) developed a mild vasoplegia, and 60 patients (7.5%) suffered from severe
      vasoplegia. Low systemic vascular resistance did not affect hospital mortality
      but was the cause for delayed extubation and prolonged stay on the intensive care
      unit (ICU). Logistic regression analysis identified temperature and duration of
      cardiopulmonary bypass, total cardioplegic volume infused, reduced left
      ventricular function, and preoperative treatment with angiotensin-converting
      enzyme (ACE)-inhibitors, out of 25 parameters, as predictive factors for early
      postoperative vasoplegia. CONCLUSION: The occurrence of low systemic vascular
      resistance following cardiopulmonary bypass is as high as 21.8%. The etiology of
      this clinical condition is most probably multifactorial. Mortality is not
      affected by vasoplegia, but there is a trend to higher morbidity and prolonged
      stay in the ICU.

PMID- 11599829
TI  - Does simultaneous antegrade and retrograde cardioplegia improve functional
      recovery and myocardial homeostasis?
AB  - BACKGROUND: The purpose of our research was to evaluate the functional recovery
      and homeostasis of myocardium during simultaneous continuous retrograde and
      antegrade cardioplegia versus continuous retrograde cardioplegia. METHODS: Forty
      patients who underwent elective coronary artery bypass grafting (CABG) were
      prospectively assigned to two clinically matched groups and analyzed in respect
      to cardioplegia protocol. Group I consisted of 24 patients who received
      continuous retrograde blood cardioplegia; Group II consisted of 16 patients who
      received simultaneous continuous ante- and retrograde cardioplegia. Hydrogen ion
      release, carbon dioxide, lactate concentration oxygen content, and oxygen
      extraction were measured from coronary sinus effluent and from the arterial line
      before and after cross-clamping of the aorta. Median changes of these parameters
      were reported. Cardiac output was measured and left and right ventricle stroke
      works were calculated. Incidence of low cardiac output, ventricular fibrillation,
      raised cardiac enzymes, and ischemic changes on electrocardiogram (ECG) were
      noted. RESULTS: In the simultaneous group, oxygen content and oxygen extraction
      recovered well after cross-clamping. The same parameters did not recover to the
      same extent in the retrograde group. These changes were notable between groups.
      Hydrogen ion, carbon dioxide, and lactate releases were comparable between
      groups. Trend toward better recovery of left ventricle stroke work index was
      encountered in the simultaneous group. CONCLUSIONS: Viability of myocardium
      measured with oxygen utilization and functional recovery is better preserved with
      simultaneous antegrade and retrograde cardioplegia. However, there is no
      difference in anaerobic metabolism markers. Thus simultaneous ante- and
      retrograde cardioplegia is probably advantageous over retrograde alone.

PMID- 11599830
TI  - Delayed chronic type A dissection following CABG: implications for evolving
      techniques of revascularization.
AB  - BACKGROUND: Postoperative dissection in some patients is related to manipulation
      of the aorta and accounts for 3% to 5% of deaths after cardiac surgery. METHODS:
      Between 1987 and 1999, 109 patients with previous cardiac operations were treated
      for chronic type A dissection. In 31 of the patients, the etiology was related to
      aortic manipulation. Twenty-one patients (17 men, 4 women; 67+/-13 years of age)
      had isolated coronary artery bypass grafting (CABG) as their first operation and
      were reviewed. The interval between operations was 52.9+/-47.3 months. RESULTS:
      Reoperation was elective in 11 patients, urgent in 10 patients. Median maximal
      aortic diameter was 6.8+/-2.1 cm; 9 patients had major aortic insufficiency. The
      intimal tear was at the partial occlusion clamp site in 12 patients (57.1%), at
      the cross-clamping site in 4 patients (19.1%), and at the proximal anastomosis in
      1 patient (4.8%); 4 patients (19.1%) had multiple tears at several sites. Cystic
      media necrosis was present in 9.5% of the patients, severe atherosclerosis in
      47.6% of the patients, and 42.9% of the patients had both. Nine patients (42.9%)
      underwent a modified Bentall procedure, 12 patients (57.1%) underwent a
      supracoronary anastomosis, and all had open distal anastomosis. There were two
      (9.5%) hospital deaths and three (14.3%) postoperative strokes. Freedom from
      cardiac or aorta-related mortality was 85.7% at a mean follow-up of 49.3 months.
      CONCLUSIONS: In patients who develop type A dissection of the aorta after
      previous CABG, the intimal tear most often is at partial occlusion clamp site.
      This complication is associated with morbidity and mortality. It remains to be
      seen whether the use of partial occlusion clamps on the pulsating and often
      diseased aorta during off-pump coronary artery bypass (OPCAB) will increase the
      risk of delayed iatrogenic dissections.

PMID- 11599831
TI  - Threshold-level repetitive transcranial electrical stimulation for intraoperative
      monitoring of central motor conduction.
AB  - OBJECT: The authors conducted a study to evaluate repetitive transcranial
      electrical stimulation (TES) to assess spinal cord motor tract function in
      individuals undergoing spine surgery, with emphasis on safety and efficacy.
      METHODS: Somatosensory evoked potentials (SSEPs) were elicited using standard
      technique. Muscle electromyographic values were measured in response to a three-
      or four-pulse train of stimulation delivered to the motor cortex via subdermal
      electrodes. They also evaluated whether changes in the minimum stimulus intensity
      (that is, threshold level) needed to elicit a response from a given muscle
      predict motor status immediately postoperatively, as well as whether changes in
      SSEP response amplitude and latency predict sensory status immediately
      postoperatively. Anesthesia was routinely induced with intravenous propofol and
      remifentanil, supplemented with inhaled nitrous oxide. Use of neuromuscular block
      was avoided after intubation. Satisfactory monitoring of muscle response to
      threshold-level repetitive TES was achieved in all but nine of the 194 patients
      studied. In contrast, cortical SSEP responses could not be elicited in 42 of 194
      individuals. In cases in which responses were present, TES-based evoked responses
      proved to be extremely accurate for predicting postoperative motor status.
      Somatosensory evoked potential monitoring was nearly as accurate for predicting
      postoperative sensory status. There were frequent instances of postoperative
      motor or sensory deficit that were not predicted by SSEP- and TES-based
      monitoring, respectively. There were no adverse events attributable to TES-based
      monitoring, although since this study ended we have had a single adverse event
      attributable to threshold-level repetitive TES. CONCLUSIONS: Intraoperative
      threshold-level repetitive TES-based monitoring of central motor conduction has
      proven to be a simple, safe, and highly accurate technique for the prevention or
      minimization of inadvertent motor deficit during surgery involving the spine or
      spinal cord.

PMID- 11599832
TI  - Surgical management of idiopathic spinal cord herniation: a review of nine cases
      treated by the enlargement of the dural defect.
AB  - OBJECT: Spinal cord herniation is a rare cause of progressive myelopathy and can
      be corrected surgically. In most previous reports, closure of the dural defect
      was the recommended procedure. The object of this paper is to describe a new
      procedure in which spinal cord constriction is released by enlarging the hiatus;
      additionally the postoperative results will be discussed. METHODS: In nine
      patients with spinal cord herniation, enlargement of the dural defect was
      performed. In eight patients, neurological deficits resolved immediately after
      surgery. In one patient with a severe preoperative neurological deficit whose
      spinal cord herniated massively, deterioration occurred postoperatively. To date,
      no recurrence of herniation has been observed. CONCLUSIONS: The goals of surgery
      are to reduce the herniation, return the spinal cord to the normal position, and
      prevent the recurrence of herniation. The use of sutures to close the dural
      defect has been the method of choice to date. The surgical space in front of the
      spinal cord, however, is insufficient to accommodate this procedure safely.
      Because symptoms are caused by the constriction of the spinal cord at the hiatus,
      surgical expansion of the hiatus allows the goals of surgery to be achieved. This
      procedure, which is technically easier and less invasive with regard to the
      vulnerable spinal cord than the closure of the dural defect, could be a viable
      alternative for the treatment of this rare disease.

PMID- 11599833
TI  - Surgical management of tethered spinal cord in adults: report of 54 cases.
AB  - OBJECT: The clinical features specific to tethered cord syndrome (TCS) in adults
      as well as factors determining outcome and prognosis have rarely been addressed
      systematically. The authors studied 56 patients, 54 of whom were treated
      surgically over the last 16 years. METHODS: In 17 patients who had been
      asymptomatic during childhood, TCS was diagnosed 8 years after onset of symptoms.
      Tethered cord syndrome was diagnosed 4 years after worsening in 39 patients with
      neurological signs or symptoms since childhood. The patients were followed for an
      average of 8 years. Features specific to adult-age presentation included
      nondermatomal pain aggravated by movement in 34 patients and conditions such as
      pregnancy and childbirth (in five of 11 pregnant patients). The most frequent
      tethering lesions were lipoma in 32, tight terminal filum in 28, and split cord
      malformation and secondary adhesions in 12 patients, respectively. Improvement or
      stabilization of symptoms at 6 months after surgery was noted in 46 (85%) of 54
      patients. Improvement in pain status was most frequent (86%) followed by
      improvements in spasticity (71%), bladder dysfunction (44%), and sensorimotor
      deficits (35%). Factors associated with adverse outcome included preoperative
      duration of neurological deficits more than 5 years and incomplete untethering.
      On average, 8 (80%) of 10 patients with incomplete untethering developed
      recurrent symptoms 5 years after surgery compared with only seven (16%) of 44
      patients in whom complete untethering was achieved. Seven patients underwent
      reoperation and in five of them stabilization of symptoms was attained. At a mean
      follow up of 8 years, 46 (85%) of the 54 surgically treated patients were in
      stable neurological condition, including those in whom reoperation was performed.
      CONCLUSIONS: Surgery for TCS is as beneficial in adults as it is in children. Its
      success depends on early diagnosis and complete untethering of the spinal cord.

PMID- 11599834
TI  - Results of applying ADCON-L gel after lumbar discectomy: the German ADCON-L
      study.
AB  - OBJECT: Failed-back syndrome is still an unsolved problem. Use of ADCON-L gel,
      already commercially available, has been proven to reduce postoperative scarring
      in animal experiments. The authors of two controlled clinical studies have also
      shown positive results when applying the gel. They did not, however, establish
      patient-oriented endpoints. The authors report a study of ADCON-L in which they
      focus on patient-oriented endpoints. METHODS: Patients with lumbar disc
      herniation were randomized to an ADCON-L-treated or control group. Therapeutic
      success was evaluated using the validated Hannover Questionnaire on Activities of
      Daily Living (FFbH) 6 months after surgery. The study took place between November
      14. 1996, and April 20, 1998, in eight neurosurgical centers in Germany. A total
      of 398 patients was recruited; 41 patients dropped out during follow up. The mean
      functional FFbH score (100 points = all activities are possible without problem;
      0 points = no activity is possible) was 78.5 points in the ADCON-L-treated group
      compared with 80 points in the control group. Furthermore, in terms of secondary
      outcome variables, the ADCON-L group did not have an advantage over the control
      group. Only the mean magnetic resonance imaging score showed a slight advantage
      of ADCON-L over the control group. CONCLUSIONS: The authors found no positive
      effect of treatment with ADCON-L gel in patients in whom one-level lumbar
      microdiscectomy was performed. Because of its rather large sample size and its
      homogeneity, the study had sufficient power to detect even small differences
      between the two groups.

PMID- 11599835
TI  - Posterior lumbar interbody fusion for revision disc surgery: review of 50 cases
      in which carbon fiber cages were implanted.
AB  - OBJECT: The authors undertook a study to assess the value of posterior lumbar
      interbody fusion (PLIF) in which carbon fiber cages (CFCs) were placed in
      patients undergoing revision disc surgery for symptoms suggesting neural
      compression with low-back pain. METHODS: The authors followed their first 50
      patients for a maximum of 5 years and a minimum of 6 months after implantation of
      the CFCs. Patients in whom magnetic resonance (MR) imaging demonstrated "simple"
      recurrent herniation did not undergo PLIF. Surgery was performed in patients with
      symptoms of neural root compression, tension signs, and back pain with focal disc
      degeneration and nerve root distortion depicted on MR imaging compatible with
      clinical signs and symptoms. In 40 patients (80%) pedicle screws were not used.
      Clinical outcome was assessed using the Prolo Functional Economic Outcome Rating
      scale. Fusion outcome was assessed using an established classification. Symptoms
      in 46 patients (92%) improved after surgery, and given their outcomes, 45 (90%)
      would have undergone the same surgery again. Two thirds of patients experienced
      good or excellent outcomes (Prolo score > or = 8) at early and late follow up.
      There was no difference in clinical outcome between those in whom pedicle screws
      were and were not implanted (p = 0.83, Mann-Whitney U-test). The fusion rate at 2
      years postsurgery was 95%. There were minimal complications, and no patients
      fared worse after surgery. No patient has undergone additional surgical
      treratment of the fused intervertebral space. CONCLUSIONS: In this difficult
      group of patients the aim remains to improve symptoms but not cure the disease. A
      high fusion rate is possible when using the CFCs. Clinical success depends on
      selecting patients in whom radiological and clinical criteria accord. Pedicle
      screws are not necessary if facet joints are preserved, and high fusion rates and
      clinical success are possible without them.

PMID- 11599836
TI  - Frameless stereotaxy for anterior spinal procedures.
AB  - OBJECT: Intraoperative image guidance provides real-time three-dimensional
      visualization and has been successfully applied in many posterior spinal
      procedures. The feasibility of applying these techniques to anterior spinal
      surgery has not been studied systematically because the anterior spine, in
      contrast to the posterior spine, lacks distinct anatomical landmarks for
      registration. The authors sought to evaluate the practicality of performing
      stereotaxy in the anterior spine in a cadaveric model. METHODS: Unilateral C4-L4
      pedicle screws were placed posteriorly in three cadaveric specimens to serve as
      unknown markers within each vertebral body. The specimens then underwent
      computerized tomography (CT) scanning, and the CT data were transferred to an
      optical tracking system. The anterior surface of the spine was registered for use
      with the stereotactic system by using a paired point-matching technique. Attached
      to a surgical drill, K-wires were placed under stereotactic guidance in a tip-to
      tip orientation with the posterior pedicle screws. A second postoperative CT scan
      was obtained, and accuracy was determined by measuring the distance between the
      tips of the K-wire and pedicle screw. The K-wires were placed tip to tip with
      pedicle screw markers in 57 vertebral levels. The mean registration error was
      1.47+/-0.04 mm, and when combined with the universal instrument registration
      error of 0.7 mm yielded an overall registration error of 2.17+/-0.04 mm. The mean
      tip-to-tip distance for all K-wires placed was 2.46+/-0.23 mm. The difference
      between the mean tip-to-tip distance and overall registration error was not
      statistically significant (p > 0.05), indicating that the K-wires were placed
      within the expected range of error. CONCLUSIONS: The results of this study
      confirmed the feasibility of performing anterior stereotactic procedures
      throughout the spine. The accuracy of the findings in this study indicates that
      anterior stereotaxy should be applicable in clinical practice.

PMID- 11599837
TI  - Lateral interscalenic multilevel oblique corpectomies to repair ventral root
      avulsions after brachial plexus injury in humans: anatomical study and first
      clinical experience.
AB  - OBJECT: Because central nervous system white matter exerts a powerful inhibitory
      effect on axonal growth, implantation of nerve grafts or rootlets into the
      cervical spinal cord following ventral root avulsion injury should, ideally, be
      performed directly through the ventral root exit zone (VRExZ), which is located
      near the anteromedial aspect of the anterior horn; the grafts/rootlets should not
      be implanted into the white matter of the lateral cord. This is not possible when
      using a conservative posterior approach. Therefore, the authors have studied the
      anatomy encountered when using the anterolateral approach and evaluated the
      technique in the particular case of avulsed ventral nerve roots. They also
      present a case illustration of the procedure, which is used currently in their
      department. METHODS: Anterior access to the rootlets is obtained using a lateral
      interscalenic approach; the vertebral artery is exposed and mobilized, and
      oblique drilling of the vertebral bodies (VBs) is performed. Because the
      articular processes and half of the VBs are preserved, fusion is not required.
      The approach allows the surgeon to expose the anterior aspect of the cervical
      dura and the entire length of the emerging spinal nerves. The anterior aspect of
      the dura is opened at the desired levels for VRExZ exposure. and the position is
      ideal for implantation of the graft/rootlets. The interscalenic dissection is
      mandatory so that the lesions of the supraclavicular plexus can be evaluated and
      repaired. If necessary, the anterior approach allows for exploration of the
      infraclavicular plexus during the same procedure. CONCLUSIONS: The use of a true
      anterior approach to the ventral rootlets appears to be a valuable and
      appropriate approach that avoids extensive laminectomy/facetectomy while
      reimplantation is performed through the anterolateral sulcus itself. In this
      approach, however, reimplantation of dorsal roots into the spinal cord remains
      impossible.

PMID- 11599838
TI  - Effect of a prosthetic disc nucleus on the mobility and disc height of the L4-5
      intervertebral disc postnucleotomy.
AB  - OBJECT: Current procedures for treatment of degenerative disc disease may not
      restore flexibility or disc height to the intervertebral disc. Recently, a
      prosthetic device, intended to replace the degenerated nucleus pulposus, was
      developed. In this biomechanical in vitro test the authors study the effect of
      implanting a prosthetic nucleus in cadaveric lumbar intervertebral discs
      postnucleotomy and determine if the flexibility and disc height of the L4-5
      motion segment is restored. METHODS: The prosthetic disc nucleus device consists
      of two hydrogel pellets, each enclosed in a woven polyethylene jacket. Six human
      cadaveric lumbar motion segments (obtained in individuals who, at the time of
      death, were a mean age of 56.7 years) were loaded with moments of +/- 7.5 Nm in
      flexion-extension, lateral bending, and axial rotation. The following states were
      investigated: intact, postnucleotomy, and after device implantation. Range of
      motion (ROM) and neutral zone (NZ) measurements were determined. Change in disc
      height from the intact state was measured after nucleotomy and device
      implantation, with and without a 200-N preload. CONCLUSIONS: Compared with the
      intact state (100%), the nucleotomy increased the ROM in flexion-extension to
      118%, lateral bending to 112%, and axial rotation to 121%; once the device was
      implanted the ROM was reduced to 102%, 88%, and 90%, respectively. The NZ
      increased the ROM to 210%, lateral bending to 173%, and axial rotation to 107%
      after nucleotomy, and 146%, 149%, 44%, respectively, after device implantation. A
      200-N preload reduced the intact and postnucleotomy disc heights by approximately
      1 mm and 2 mm, respectively. The original intact disc height was restored after
      implantation of the device. The results of the cadaveric L4-5 flexibility testing
      indicate that the device can potentially restore ROM, NZ, and disc height to the
      denucleated segment.

PMID- 11599839
TI  - Comparison of the biomechanics of hydroxyapatite and polymethylmethacrylate
      vertebroplasty in a cadaveric spinal compression fracture model.
AB  - OBJECT: Polymethylmethacrylate (PMMA) has long been used in the stabilization and
      reconstruction of traumatic and pathological fractures of the spine. Recently,
      hydroxyapatite (HA), an osteoconductive, biocompatible cement, has been used as
      an alternative to PMMA. In this study the authors compare the stabilizing effects
      of the HA product, BoneSource, with PMMA in an experimental compression fracture
      of L-1. METHODS: Twenty T9-L3 cadaveric spine specimens were mounted individually
      on a testing frame. Light-emitting diodes were placed on the neural arches as
      well as the base. Motion was tracked by two video cameras in response to applied
      loads of 0 to 6 Nm. The weight-drop technique was used to induce a reproducible
      compression fracture of T-11 after partially coring out the vertebra. Load
      testing was performed on the intact spine. postfracture, after unilateral
      transpedicular vertebroplasty with 7 to 10 ml of PMMA or HA, and after flexion
      extension fatiguing to 5000 cycles at +/- 3 Nm. No significant difference between
      the HA- and PMMA cemented-fixated spines was demonstrated in flexion, extension,
      left lateral bending, or right and left axial rotation. The only difference
      between the two cements was encountered before and after fatiguing in right
      lateral bending (p < or = 0.05). CONCLUSIONS: The results of this study suggest
      that the same angular rigidity can be achieved using either HA or PMMA. This is
      of particular interest because HA is osteoconductive, undergoes remodeling, and
      is not exothermic.

PMID- 11599840
TI  - Comparison of spinal cord gray matter and white matter softness: measurement by
      pipette aspiration method.
AB  - OBJECT: Although the gray matter of the spinal cord has been thought to be softer
      than the white matter, there is no evidence to support this belief. Because the
      spinal cord is extremely soft, it has been difficult to measure the mechanical
      properties of the gray and white matter. The modulis of elasticity of the gray
      and white matter were measured in situ by using a pipette aspiration method.
      METHOD: The spinal cord specimens were excised from Japanese white rabbits.
      Specimens were cut to display the surfaces of axial, frontal, and sagittal
      sections. The surfaces of the gray and white matter were aspirated using a 0.8-mm
      inner-diameter glass pipette while monitoring with a video microscope, and the
      deformed length in the pipette was measured on a monitor. In each case the
      modulus of elasticity was calculated by comparing the relationship between the
      aspiration pressure and aspirated volume of the specimen with that determined by
      finite element analysis. The moduli of elasticity of the gray and white matter
      were 3.4+/-1.4 kPa (mean +/- standard deviation) and 3.4+/-0.9 kPa in the axial
      section, 3+/-0.3 kPa and 3.5+/-0.5 kPa in the frontal section, and 3.5+/-0.9 kPa
      and 2.8+/-0.4 kPa in the sagittal section, respectively. CONCLUSIONS: No
      significant difference in modulus of elasticity was shown between the gray and
      white matter of the spinal in sections made in various directions.

PMID- 11599841
TI  - Therapeutic options for meningeal melanocytoma. Case report.
AB  - Meningeal melanocytomas are uncommon lesions. They are generally considered to be
      benign tumors that derive from leptomeningeal melanocytes. A rare case of a
      metastatic spinal meningeal melanocytoma is presented. All relevant cases
      reported in literature since 1972, when the term "meningeal melanocytoma" was
      first used, were reviewed. Rates of tumor recurrence from 1 to 5 years were
      calculated for this rare lesion, based on published data and on additional
      information obtained from personal contact with most of the authors. Recurrency
      rates of 47 patients suitable for evaluation were correlated with the different
      therapeutic approaches. Complete tumor resection alone and incomplete resection
      alone followed by irradiation appeared to be superior to incomplete resection
      alone in terms of disease-free survival. Statistical significance was achieved
      for complete tumor resection at follow up between I and 4 years (range p = 0.010
      0.050) and for incomplete resection combined with radiotherapy after 2 years (p =
      0.034). Complete tumor resection should be considered the best therapeutic
      option, followed by incomplete resection combined with postoperative
      radiotherapy.

PMID- 11599842
TI  - Spinal meningioma after treatment for Hodgkin disease. Case report.
AB  - Long-term survivors of Hodgkin disease may develop second primary tumors caused
      by the mutagenic effects of radio- and chemotherapy. The authors describe the
      case of a 35-year-old woman who presented with an unusual meningioma of the
      cervical spine 9 years after undergoing combined-modality treatment for Hodgkin
      disease. To the authors' knowledge, this is the first report of spinal meningioma
      as a complication of such therapy. Whereas radiation-induced intracranial
      meningiomas are well described in the literature, treatment-induced meningiomas
      of the spine have not been widely recognized.

PMID- 11599843
TI  - Segmental neurofibromatosis-induced spinal cord compression. Case report.
AB  - Spinal segmental neurofibromatosis (NF) is a rare entity. To date, patients in
      reported cases of segmental NF (or NF5) have harbored neurofibromas involving the
      peripheral nerves only. The author reports a rare case of segmental NF that
      caused spinal cord compression in a 40-year-old woman who presented with a 6
      month history of intercostal neuralgia. Examination revealed mild lower-extremity
      weakness and dysesthesia in the right-sided T-9 dermatome. Magnetic resonance
      imaging revealed three neurofibromas involving the T-9 region, which were
      excised, and the patient's neuralgic pain was resolved postoperatively.
      Traditionally, it has been believed that segmental NF involved only the
      peripheral nerves. The present case illustrates that although rare, spinal cord
      compression can also occur in patients with segmental NF.

PMID- 11599844
TI  - Transoral resection of axial lesions augmented by intraoperative magnetic
      resonance imaging. Report of three cases.
AB  - Transoral decompression of the cervicomedullary junction may be compromised by a
      narrow corridor in which surgery is performed, and thus the adequacy of surgical
      decompression/resection may be difficult to determine. This is problematic as the
      presence of spinal instrumentation may obscure the accuracy of postoperative
      radiological assessment, or the patient may require reoperation. The authors
      describe three patients in whom high-field intraoperative magnetic resonance (MR)
      images were acquired at various stages during the transoral resection of C-2
      disease that had caused craniocervical junction compression. All three patients
      harbored different lesions involving the cervicomedullary junction: one each of
      plasmacytoma and metastatic breast carcinoma involving the odontoid process and C
      2 vertebral body, and basilar invagination with a Chiari I malformation. All
      patients presented with progressive myelopathy. Surgical planning MR imaging
      studies performed after the induction of anesthesia demonstrated the lesion and
      its relationship to the planned surgical corridor. Transoral exposure was
      achieved through placement of a Crockard retractor system. In one case the soft
      palate was divided. Interdissection MR imaging revealed that adequate
      decompression had been achieved in all cases. The two patients with carcinoma
      required placement of posterior instrumentation for stabilization. Planned
      suboccipital decompression and placement of instrumentation were averted in the
      third case as the intraoperative MR images demonstrated that excellent
      decompression had been achieved. Intraoperatively acquired MR images were
      instrumental in determining the adequacy of the decompressive surgery. In one of
      the three cases, examination of the images led the authors to change the planned
      surgical procedure. Importantly, the acquisition of intraoperative MR images did
      not adversely affect operating time or neurosurgical techniques, including
      instrumentation requirements.

PMID- 11599845
TI  - Unicameral bone cyst of a cervical vertebral body and lateral mass with
      associated pathological fracture in a child. Case report and review of the
      literature.
AB  - The authors present the case of a 10-year-old girl with a history of cervical
      trauma in whom a cystic lesion was found to involve all three columns of C-7 with
      evidence of pathological fracture. Computerized tomography scanning revealed a
      lytic lesion with sclerotic margins involving the left vertebral body, pedicle,
      lateral mass, and lamina of C-7 with an associated pathological compression
      fracture. Magnetic resonance imaging demonstrated mixed signal on both T1- and T2
      weighted sequences, with cystic and enhancing solid portions. Magnetic resonance
      angiography demonstrated anterior displacement of the left vertebral artery at C
      7. The patient underwent C-7 subtotal corpectomy and posterior resection of the
      tumor mass; anterior and posterior fusion were performed in which instrumentation
      was placed. Histological examination disclosed cystic areas lined by
      fibromembranous tissue with calcification and osteoid deposits consistent with
      unicameral bone cyst. Of the four previously reported cases of unicameral bone
      cysts in the cervical spine, none involved all three columns simultaneously or
      was associated with pathological fracture. The most common differential
      diagnostic considerations for cystic lesions in the spine are aneurysmal bone
      cyst, osteoblastoma, or giant cell tumor of bone. Unicameral bone cyst, in this
      location, although rare, must be considered in the differential diagnosis and may
      require resection and spinal reconstruction.

PMID- 11599846
TI  - Further cranial settling of the upper cervical spine following odontoidectomy.
      Report of two cases.
AB  - A variety of diseases may affect the craniovertebral junction and require a
      decompressive and fusion procedure. Craniovertebral junction instability is
      expected after a fusion procedure. The authors describe two patients with basilar
      invagination who underwent transoral odontoidectomy and occipitocervical
      fixation. Despite an uneventful immediate postoperative course, further cranial
      settling of the C-2 vertebral body (VB) was demonstrated. One patient experienced
      neurological deterioration and required a second decompressive procedure, whereas
      the second patient was asymptomatic and required no additional surgery. It was
      concluded that the odontoidectomy may have led to horizontal separation of the C
      1 lateral masses, resulting in further cranial settling of the C-2 VB.
      Preservation of one aspect of the C-1 anterior arch minimizes C-1 lateral mass
      offset and, in turn, further cranial settling of the C-2 VB. In addition, a more
      rigid fixation of C-2 may minimize the possibility of horizontal separation of
      the C-1 lateral masses after transoral odontoidectomy.

PMID- 11599847
TI  - Ectopic fingerlike structure in the thoracic region. Case report.
AB  - The authors present a case of a rare cutaneous lesion resembling a human finger
      that protruded from the posterior thoracic region of a 7-month-old girl who was
      examined after the fingerlike protrusion was noted at birth. The protrusion
      measured 3 cm in length and 1 cm in diameter. It was located at the level of T-12
      and was surrounded by angiomatous and lipomatous tissue. A computerized
      tomography scan demonstrated three bones in the protrusion. including deformities
      of the T-9 and T-10 and T-11 dysraphism. Magnetic resonance imaging revealed a
      hyperintense signal on the T1-weighted sequence and a hypointense signal on the
      T2-weighted sequence, which was visualized at the attachment to the spinal cord
      from T9-11. After removal of the fingerlike structure and subcutaneous mass, a
      T10-11 laminectomy and removal of the intradural mass were performed.
      Histological examination showed that the appendage was composed of nail, three
      bones, cartilage, and normal skin. This appendage can be recognized not only as a
      variant type of caudal appendage but as an ectopic finger and fingernail. The
      authors discuss the developmental differences among the protrusion in the present
      case and ordinary caudal appendages.

PMID- 11599848
TI  - Delayed aortic rupture caused by an implanted anterior spinal device. Case
      report.
AB  - The authors describe a case of delayed aortic rupture following the application
      of a smooth-rod Kaneda (SRK) instrument. This is a rare but critical complication
      of anterior spinal fusion in which instrumentation is placed, and the authors
      wish to draw attention to the possible complications arising from such surgery. A
      few cases of this complication were reported in 1986. No reports have been
      published since then; perhaps because techniques and implant design have
      improved. In this case, a 53-year-old man suffered a T-11 fracture and related
      paraparesis, and he underwent decompression and anterior fusion in which an iliac
      bone graft was placed using an SRK device. Although his neurological deficit
      resolved postoperatively, nonunion of the grafted bone caused progressive
      kyphosis of the thoracolumbar spine. Twenty months after surgery, he complained
      of progressive gastrointestinal symptoms, and a delayed aortic rupture with a
      pseudoaneurysm was found surrounding the implant. The aortic pseudoaneurysm was
      replaced with an artificial vessel, and the SRK device was removed immediately.
      Delayed aortic rupture associated with anterior instrumentation is extremely rare
      but can occur. Even if the design of the implants can be improved, the placement
      of implants near the aorta and subsequent changes in the close anatomical
      relationship between the aorta and the implant eventually may result in this life
      threatening complication. Careful follow-up examination and early removal of the
      implant, if necessary, are important.

PMID- 11599849
TI  - Gas-filled intradural cyst of the lumbar spine. Case report.
AB  - The authors describe the case of a gas-filled intradural cyst of the lumbar spine
      that caused radicular pain. The cyst was similar to an intervertebral vacuum disc
      phenomenon and the cystic gas collection resembled the features of gas-containing
      pseudocyst, herniated intradiscal gas, or free gas, all of which have been found
      in the epidural space.

PMID- 11599850
TI  - Intramuscular myxoma causing lumbar radiculopathy. Case report and review of the
      literature.
AB  - The authors present the rare case of a myxoma, a benign soft-tissue tumor of
      mesenchymal origin noted for occurring in the left atrium of the heart, which was
      found in the lumbar paraspinal muscles of an 80-year-old woman. This patient
      experienced low-back pain for over 20 years and had noted its increasing severity
      with the development of an L-5 radiculopathy over a 3-month period. Magnetic
      resonance imaging of the lumbar spine revealed a large paraspinal mass that
      invaded the L-5 vertebral body and the left foramen of L5-S1. A computerized
      tomography-guided biopsy sampling procedure was performed, and examination of the
      specimen revealed an intramuscular myxoma. The patient underwent resection of the
      tumor and nerve root decompression. The diagnosis of intramuscular myxoma was
      confirmed, and the patient experienced complete resolution of her presenting
      symptoms. This patient represents the third reported case (the first in the
      English-language literature) of an intramuscular (paraspinal) myxoma presenting
      with lumbar nerve root compression.

PMID- 11599851
TI  - Total en bloc lumbar spondylectomy. Case report.
AB  - The authors describe a technique for total en bloc spondylectomy that can be used
      for lesions involving the lumbar spine. The technique involves a combined
      anterior-posterior approach and takes into account the unique anatomy of the
      lumbar spine. This technique allows for the en bloc resection of lumbar vertebral
      tumors, thus optimizing outcome while minimizing the risk of neurological injury.
      The technique is described in detail with the aid of neuroimaging studies,
      photographs of gross pathological specimens, and illustrations, and a discussion
      of other authors' experiences is provided for comparison.

PMID- 11599852
TI  - Intramedullary Ewing sarcoma of the spinal cord: consequences of molecular
      diagnostics. Case report.
AB  - Molecular biological techniques have begun to transform modern medicine. These
      techniques have shown promise in the pathological diagnosis of difficult or
      uncommon tumors. Accurate molecular diagnosis of the small round-cell tumors, for
      example, is especially important because divergent therapies may be required to
      eradicate such disparate lesions as neuroblastoma, lymphoma, rhabdomyosarcoma,
      central primitive neuroectodermal tumors/medulloblastoma, or Ewing sarcoma (ES).
      The authors present an unusual case of a primary, extraosseous ES arising from
      the intramedullary spinal cord, in which molecular studies were required for
      specific diagnosis and therapeutic guidance.

PMID- 11599853
TI  - Traumatic thoracic disc herniation. Case illustration.

PMID- 11599854
TI  - Tethered spinal cord with double lipomas. Case illustration.

PMID- 11599855
TI  - Vertebral melorheostosis. Case illustration.

PMID- 11599856
TI  - Remote hemorrhage.
AB  - The authors report a case of infra- and supratentorial intracerebral hemorrhage
      complicating the postoperative course of a patient who had undergone surgical
      removal of a cervical schwannoma with an hourglass configuration. To their
      knowledge, this is the first case in which this neurosurgical procedure was
      followed by such a complication. Possible mechanisms are discussed; however,
      pathological events leading to this complication are unclear. The development of
      new neurological deficits not attributable to the surgical procedure should
      suggest this possibility.

PMID- 11599858
TI  - Open book fusion.

PMID- 11599857
TI  - Bilateral vocal cord paralysis.

PMID- 11599859
TI  - Delay of care in discs.

PMID- 11599860
TI  - Complication of cages.

PMID- 11599861
TI  - Complication of cages.

PMID- 11599862
TI  - Complication of cages.

PMID- 11599863
TI  - Stress-induced changes in subendocardial tissue texture in hypertrophic
      cardiomyopathy: an echocardiographic videodensitometric study.
AB  - BACKGROUND: Myocardial ischemia changes myocardial acoustic properties, inducing
      increase of integrated backscatter and blunting of cyclic variation of
      backscatter. Stress-induced subendocardial underperfusion has been demonstrated
      in patients with hypertrophic cardiomyopathy (HCM). AIM: To evaluate the
      potential of a videodensitometric approach in assessing transmural ultrasonic
      tissue changes in HCM during dipyridamole infusion. METHODS: Twenty-two patients
      (13 males, 50+/-12 years) with HCM underwent dipyridamole echo testing (DET).
      Myocardial gray levels amplitude was calculated off-line on digitized images in
      the left subendocardial (LV-endo), right subendocardial (RV-endo) region of the
      interventricular septum and posterior wall (long axis parasternal view). RESULTS:
      The thickness of the interventricular septum and posterior wall was 1.9+/-0.3 and
      1.17+/-2.1 cm, respectively. In the LV-endo layer, the cyclic variation was
      blunted during DET (rest = 37+/-14 vs. DET 27+/-20%, p < 0.02). In the RV-endo
      layer and posterior wall, no changes occurred. In the LV-endo layer of the
      septum, blunting of cyclic variation was more pronounced in the 10 patients with
      than in the 12 without ST-segment depression during DET (21.2+/-14.7% vs. 43.8+/
      15.8, p < 0.01). CONCLUSIONS: In HCM patients, DET induced blunting of cyclic
      variation without the evidence of wall motion abnormalities. This reduction was
      more pronounced when electrocardiographic signs of ischemia were simultaneously
      elicited by DET.

PMID- 11599864
TI  - An enhanced method for left ventricular volume and ejection fraction by triggered
      harmonic contrast echocardiography.
AB  - To elucidate the validity and reproducibility of the use of intravenous echo
      contrast agent in the evaluation of left ventricular (LV) performance, we
      measured LV volume and ejection fraction (EF) in 42 patients with triggered
      harmonic contrast imaging (THCI), compared with continuous harmonic imaging
      without contrast agent (CHI) and with cineventriculography (CVG). In 10 of 42
      patients, THCI improved LV border delineation which could not be obtained even
      with CHI. LV end-diastolic, end-systolic volumes and EF by both CHI and THCI
      correlated well with those by CVG. Although LV volumes are underestimated, THCI
      lessened the mean differences to about in half, compared with CHI. The observer
      variabilities obtained using THCI were smaller than those by CHI. These results
      indicate the validity of LV enhancement and the measurement of EF using THCI. We
      suggest that this method noninvasively provides more accurate LV systolic
      function with the acceptable reproducibility.

PMID- 11599865
TI  - Echocardiographic evaluation of left and right ventricular function in mild
      hypertension.
AB  - Thirty-one cases of untreated 'mild hypertension' and equal number of age and sex
      matched controls with 'normal' blood pressure were evaluated by echocardiography.
      Patients with mild hypertension had significantly increased left ventricular mass
      index, concentric remodeling, and diastolic dysfunction. Thickness of right
      ventricular anterior wall, flow velocities across tricuspid and pulmonary valves
      were also significantly higher in hypertensives. Pulmonary flow acceleration time
      was significantly less in hypertensives. On multiple regression analysis, mitral
      valve 'A' wave velocity alone correlated with systolic blood pressure. Other
      echocardiographic variables did not have any relation with blood pressure
      readings. Height, weight, body surface area and body mass index could also
      explain only around 50% of variability in echocardiographic parameters. Cardiac
      structure and functions in hypertensives are affected by factors other than blood
      pressure reading, body surface area or body mass index. Routine echocardiography
      can be useful in identifying those patients of mild hypertension who have
      disproportionate increase in left ventricular mass or disproportionate impairment
      of diastolic functions.

PMID- 11599866
TI  - The higher likelihood of developing cardiomegaly during follow-up in patients
      with syndrome X and abnormal thallium-201 myocardial perfusion SPECT.
AB  - 'Syndrome X' describes patients with exertional chest pain and a normal coronary
      arteriogram. In some patients, acute myocardial ischemia can be demonstrated by
      regional myocardial perfusion defects on thallium-201 exercise test. However,
      some patients with typical angina have normal perfusion on thallium-201 heart
      scintigraphy. It is not clear whether there are different prognoses for patients
      with normal and abnormal thallium studies. In this study, the clinical features,
      long term follow-up and clinical results of syndrome X patients with normal and
      abnormal thallium studies were evaluated to determine the differences between
      these two groups. Fifty-nine patients (52 males, seven females, mean age 62+/-6
      years) with syndrome X were enrolled and divided into two groups on the basis of
      results of thallium-201 heart scintigraphy. Group I was comprised of 22 patients
      with normal thallium-201 perfusion scan and group II was comprised of 37 patients
      with abnormal thallium-201 heart scan. All subjects received coronary
      arteriography, exercise test, thallium-201 myocardial SPECT, ejection fraction of
      left ventricle, echocardiography, blood analysis and long term follow-up with
      questionnaire for 10 years. Lower maximal rate-pressure product and higher angina
      scores were found in group II. More patients developed cardiomegaly (nine of 33
      patients) in group II than in group I (one of 21 patients). Both groups, however,
      were at low risk for cardiac events (cardiac death or myocardial infarction).

PMID- 11599867
TI  - Clinical validation of an automated boundary tracking algorithm on cardiac MR
      images.
AB  - The goal of this research was to develop an automated algorithm for tracking the
      borders of the left ventricle (LV) in a cine-MRI gradient-echo temporal data set.
      The algorithm was validated on four patient populations: healthy volunteers and
      patients with dilated cardiomyopathy (DCM), left ventricular hypertrophy (LVH),
      or left ventricular aneurysm (LVA). A full tomographic set (approximately 11
      slices/case) of short-axis images through systole was obtained for each patient.
      Initial endocardial and epicardial contours for the end-diastolic (ED) and end
      systolic (ES) frames were manually traced on the computer by an experienced
      radiologist. The ED tracings were used as the starting point for the algorithm.
      The borders were tracked through each phase of the temporal data set, until the
      ES frame was reached (approximately 7 phases/slice). Peak gradients along equally
      spaced chords calculated perpendicular to a centerline determined midway between
      the endocardial and epicardial borders were used for border detection. This
      approach was tested by comparing the LV epicardial and endocardial volumes
      calculated at ES to those based on the manual tracings. The results of the
      algorithm compared favorably with both the endocardial (r2 = 0.72 - 0.98) and
      epicardial (r2 = 0.96 - 0.99) volumes of the tracer.

PMID- 11599868
TI  - A comparison of prospective and retrospective respiratory navigator gating in 3D
      MR coronary angiography.
AB  - A comparison between the prospective and retrospective respiratory navigator
      gating in MR coronary angiography was performed with eight normal subjects. A
      three-dimensional (3D) ECG-gated fast gradient echo pulse sequence was used for
      image data acquisition. The results show that the MR coronary angiography
      obtained using retrospective gating retains a considerable amount of motion
      artifacts. In this study, the images acquired using prospective navigator gating
      demonstrated significantly reduced motion artifacts (p = 0.009), improved vessel
      visibility (p = 0.021) with reduced imaging time (p = 0.013) compared to the
      images obtained using retrospective navigator gating.

PMID- 11599869
TI  - MR imaging of arrhythmogenic right ventricular dysplasia.
AB  - Arrhythmogenic right ventricular displasia (ARVD) is a heart disease
      characterized by a total or partial fat replacement of the myocardium.
      Echocardiography, which has been most commonly used for the diagnosis of ARVD,
      usually only demonstrates right ventricular enlargement with associated
      hypokinesia and with normal left ventricular chamber size. Angiocardiography is
      very effective in the evaluation of ARVD, especially, in the detection of wall
      motion abnormalities and bulgings. However, angiocardiography is invasive.
      Magnetic resonance imaging is a non-invasive, repeatable technique, which allows
      a more accurate evaluation of the right ventricular chamber and free wall.
      Therefore MRI is very effective in the differentiation of the high signal
      intensity of the fat from other medium intensity tissue, such as muscle, and in
      detection of fibro-fatty replacement of myocardium. It provides an accurate
      assessment of right-chamber enlargement, right ventricle outflow tract ectasia
      and wall motion abnormalities by cine-MR GE technique.

PMID- 11599870
TI  - Isolated noncompaction of the ventricular myocardium: ultrafast computed
      tomography and magnetic resonance imaging.
AB  - This study was undertaken to evaluate the feasibility of ultrafast computed
      tomography (CT) and magnetic resonance imaging (MRI) for anatomical and
      pathophysiological diagnosis of isolated noncompaction of the left ventricular
      myocardium (INVM) compared with other imaging modalities including thallium
      myocardial imaging. Six patients, three sets of siblings, ranging in age from 13
      to 18 years, were included in this study. Two-dimensional echocardiograms
      revealed numerous prominent trabeculations and deep intertrabecular recesses in
      one or more ventricular wall segments in all cases. Thallium-201 myocardial
      imaging disclosed a hypoperfusion area corresponding to the zones where
      noncompacted ventricular myocardium was localized. Ultrafast CT showed early
      defects of varying degrees and rate enhancement of the noncompacted ventricular
      myocardium, implying fibrosis in this area. MRI disclosed inner zones of
      noncompacted myocardium distinguishable from thin outer zones of compacted
      myocardium. T2-weighted imaging revealed high intensity areas at the apex of the
      left ventricle, suggesting disturbed microcirculation due to fibrosis, thrombus
      formation, and hypokinesis. Cine MRI revealed hypokinesis of the noncompacted
      ventricular wall during the cardiac cycle. In conclusion, ultrafast CT and MRI
      provide high-resolution imaging of noncompacted myocardium, and also
      pathophysiological details regarding this rare disease.

PMID- 11599871
TI  - Localization of late potential sources in myocardial infarction.
AB  - INTRODUCTION: Late potentials (LP) are markers of arrhythmogenic events after
      myocardial infarction (MI). The localization of LP sources would help to identify
      arrhythmogenic myocardium. The purpose of this study was to localize these LP
      sources from non-invasive body surface mapping data. METHODS AND RESULTS: Six
      patients were investigated with cardiac MRI and signal averaged 62-lead
      magnetocardiography after MI. Three of them were suffering from sustained
      ventricular tachycardia (VT). Sophisticated computer algorithms were used in
      order to compute the current density on the surface of the left ventricle. We
      compared these current density distributions for the entire QRS complex and the
      high frequency LP signals. In the three patients which had premature ventricular
      complexes (PVCs) we localized the exit sites of these arrhythmias. We found a
      close matching of the low current density areas based on the QRS complexes and
      the high current density areas based on the LP signals. These areas predominantly
      corresponded to sites of the infarctions. Exit sites of PVCs were located close
      to these areas. CONCLUSIONS: By means of sophisticated computer algorithms we
      were able to localize LP sources. This would be useful in steering catheter
      ablation and coronary revascularization therapies. However, the method has to be
      proven with the help of invasive mapping in a larger number of patients.

PMID- 11599872
TI  - Measuring hearing aid benefit using a willingness-to-pay approach.
AB  - The value associated with self-perceived hearing aid benefit was assessed using a
      "willingness-to-pay" (WTP) approach. Abbreviated Profile of Hearing Aid Benefit
      (APHAB) data were obtained from 79 veterans who also indicated how much they were
      willing to pay for each hearing aid. The results of a multiple regression
      analysis revealed that veterans were willing to pay $22.06 more for a hearing aid
      for each 1-point increase in APHAB global benefit. A second multiple regression
      analysis revealed that the APHAB subscale scores for Ease of Communication (EC)
      benefit and understanding speech in Background Noise (BN) benefit, as well as
      income level, were all significant predictors of WTP. In addition, each 1-point
      increase in EC, BN, and Reverberation benefit increased the value associated with
      amplification by $16.32, $16.88, and $13.78, respectively. Each 1-point increase
      in the Aversiveness of Sounds subscale decreased the value associated with
      amplification by $7.63. The mean WTP across all income groups was $981.71 per
      hearing aid. These data are interpreted to support the use of WTP as a valid
      measure of hearing aid benefit.

PMID- 11599873
TI  - Evaluation of the Computer-assisted Speech Perception Assessment Test (CASPA).
AB  - Interlist equivalency and short-term practice effects were evaluated for the
      recorded stimuli of the Computer-Assisted Speech Perception Assessment (CASPA)
      Test. Twenty lists, each consisting of 10 consonant-vowel-consonant words, were
      administered to 20 adults with normal hearing. The lists were presented at 50 dB
      SPL (Leq) in the presence of spectrally matched steady-state noise (55 dB SPL
      Leq). Phoneme recognition scores for the first list presented were significantly
      lower than for the second through the twentieth list presented, indicating a
      small practice effect. Phoneme scores for 4 of the lists (3, 6, 7, and 16) were
      significantly higher than scores for the remaining 16 lists by approximately 10
      percentage points. Eliminating the effects of interlist differences reduced the
      95 percent confidence interval of a test score based on a single list from 18.4
      to 16.1 percentage points. Although interlist differences have only a small
      effect on confidence limits, some clinicians may wish to eliminate them by
      excluding lists 3, 6, 7, and 16 from the test. The practice effect observed here
      can be eliminated by administering one 10-word practice list before beginning the
      test.

PMID- 11599874
TI  - Similarities and differences in distortion-product otoacoustic emissions among
      four FDA-approved devices.
AB  - Similarities and differences in distortion-product otoacoustic emissions (DPOAEs)
      among four Food and Drug Administration (FDA) approved devices were assessed
      quantitatively. DPOAEs were recorded from 42 adult subjects (84 ears) ranging in
      age from 19 to 40 years. All subjects had hearing thresholds of 20 dB HL or
      better for the test frequencies from 0.25 to 8.0 kHz and normal acoustic
      immittance findings. DPOAEs were collected in a quiet non-sound-treated room.
      DPOAE measurement parameters included an f2/f1 ratio of approximately 1.2, with
      f1 at 65 dB SPL (L1) and f2 at 55 dB SPL (L2). There were no significant
      differences in the mean emissions levels among the four devices. This
      investigation showed that validity criteria, pass criteria, and strategies for
      DPOAE measurements interact to produce varying pass and refer results. However,
      when DPOAEs are obtained with consistent validity criteria, pass criteria, and
      strategies for measurement, the results are remarkably consistent.

PMID- 11599875
TI  - Auditory-verbal graduates: outcome survey of clinical efficacy.
AB  - This project is an update of an earlier study on American and Canadian graduates
      of auditory-verbal programs. Survey research was conducted to obtain information
      on a variety of topics. Overall, the current results again indicated that the
      majority of respondents were integrated into "regular" or "typical" learning and
      living environments. In view of the earlier identification of hearing loss and
      the early fitting of sensory aids and availability of cochlear implant
      technology, coupled with intervention that emphasizes auditory learning, it is
      suggested that today's infants have the potential to become independent,
      participating, and contributing citizens in mainstream society.

PMID- 11599876
TI  - Effect of preferred volume setting on speech audibility in different hearing aid
      circuits.
AB  - This study compared preferred volume setting for linear peak clipping,
      compression limiting, and wide dynamic range compression (WDRC) amplification and
      quantified speech audibility at the preferred volume setting for each
      amplification type. Ten listeners with mild-to-moderate hearing loss were fitted
      monaurally with a behind-the-ear hearing aid programmed sequentially with WDRC,
      compression limiting, and linear peak clipping amplification. Speech was
      presented in quiet and in noise at a range of input levels. In each condition,
      the listener adjusted the volume for maximum clarity. Signal levels were measured
      using a probe microphone system. There was no significant difference in speech
      audibility between amplification strategies for any speech level regardless of
      the presence or absence of background noise. These results imply that the
      improved audibility advantage of WDRC over linear amplification demonstrated in
      controlled environments may not be maintained in situations where the hearing aid
      wearer controls the volume.

PMID- 11599877
TI  - Evaluation of a Revised Speech in Noise (RSIN) test.
AB  - A revised version of the Speech in Noise (SIN) test was developed by reallocating
      the recorded test material on the compact disc into different lists (blocks). The
      goal was to increase the equivalence and reliability of the test blocks to
      enhance their usefulness in research settings. The Revised Speech in Noise test
      has four blocks of sentences. Each block comprises twice as many sentences as in
      the original SIN test. There are also practice sentences for each condition.
      Forty-two elderly subjects with normal hearing for their age and gender provided
      data on the equivalence of the new test blocks. The remaining inequalities in
      mean scores were mostly eliminated using score weighting. Critical differences
      were developed to promote interpretation of scores from the same individual under
      different conditions. The revisions substantially improved the equivalence of
      test blocks and their sensitivity to performance changes. Increased test time is
      the associated drawback.

PMID- 11599878
TI  - Are the benefits worth the cost?

PMID- 11599879
TI  - Liver cancer in atomic-bomb survivors: histological characteristics and
      relationships to radiation and hepatitis B and C viruses.
AB  - Histological features of primary liver cancer among atomic-bomb survivors and
      their relationship to hepatitis B (HBV) and C viral (HCV) infections are of
      special interest because of the increased risk of liver cancer in persons exposed
      to ionizing radiation and the high and increasing liver cancer rates in Japan and
      elsewhere. We conducted a pathology review of liver cancers occurring from 1958
      to 1987 among subjects in the 120,321 member cohort of 1945 Hiroshima and
      Nagasaki residents. A panel of pathologists classified tumor histological types
      and defined accompanying cirrhotic changes of the liver. Archival tissue samples
      were assessed for HBV using pathology stains and PCR. Reverse transcriptase (RT)
      PCR was used to determine HCV status. We used unconditional logistic regression
      to compare 302 hepatocellular carcinoma (HCC) cases to 53 cholangiocarcinoma (CC)
      cases, adjusting for age, year of diagnosis, sex and viral status. Cirrhotic
      changes occurred significantly more often among HCC than CC cases (76% in HCC and
      6% in CC). Compared to CC cases, HCC cases were 10.9 times more likely to be HBV
      positive (95% confidence interval: 2.1-83.2) and 4.3 times more likely to be HCV
      positive (95% confidence interval: 1.1-20.5). No significant differences were
      found between HCC and CC cases in radiation exposures. The predominance of HCC in
      the atomic-bomb survivors follows the background liver cancer pattern in Japan.
      Our findings suggest that HBV and HCV are involved in the pathogenesis of HCC
      with or without cirrhosis and are significantly less important in that of CC.

PMID- 11599880
TI  - Time course of reoxygenation in experimental murine tumors after carbon-beam and
      X-ray irradiation.
AB  - We compared the tumor reoxygenation patterns in three different murine tumor cell
      lines after X-irradiation with those after carbon-beam irradiation using a heavy
      ion medical accelerator (HIMAC) system. The tumors of the cell lines SCCVII,
      SCCVII-variant-1 and EMT6 on the hind legs of mice received local priming
      irradiation with a carbon-beam (8 Gy, 73 keV/microm in LET, 290 MeV/u, 6 cm SOBP)
      or X-rays (13 Gy, 250 kVp). After various intervals, the mice were given whole
      body test irradiation (16 Gy. 250 kVp X-ray) either in air or after they were
      killed. The hypoxic fractions were estimated as the proportions of the surviving
      fractions of the tumors in killed mice to those in air-breathing mice. In the
      SCCVII tumors, the hypoxic fractions at 0.5 h were 50% and 21% (p < 0.05) after
      the priming X-irradiation and carbon-beam irradiation, respectively. In the
      SCCVII-variant-1 tumors, the hypoxic fractions were 85% and 82% at 0.5 h, 84% and
      20% at 12 h (p < 0.01), and 21% and 31% at 24 h after X-ray and after carbon-beam
      irradiation, respectively. In the EMT6 tumors, the reoxygenation patterns after X
      irradiation and carbon-beam irradiation were quite similar. We concluded that the
      reoxygenation pattern differed among the three tumor cell lines, and that
      reoxygenation tended to occur more rapidly after carbon-beam irradiation than
      after X-irradiation for SCCVII and SCCVII-variant-1 tumors.

PMID- 11599881
TI  - Age-dependent exposure to radioactive iodine (131I) in the thyroid and total body
      of newborn, pubertal and adult fischer 344 rats.
AB  - Female rats of the Fischer 344 strain at ages of 1, 4 and 9 weeks were exposed to
      131I intraperitoneally with activities of 0.38, 1.03 and 3.42 kBq per gram of
      body weight under the condition of iodine deficiency. The absorbed doses in the
      thyroid increased linearly depending on the injected activities. Irradiation at 1
      week old caused heavier exposure than those at 4 and 9 weeks old by 7.5 and 7.7
      times, respectively; however, damage of the thyroid tissue was more obvious in
      the 4-week-old groups than in the 1-week-old groups. The absorbed doses in the
      total body were proportional to the square root of the injected activities. The
      one-week-old groups were exposed more heavily than the 4- and 9-week-old groups
      by 3.6 and 4.7 times, respectively, shown by the slow excretion of 131I with the
      values of effective half-life of 131I activity (Teff). An IDD-treatment was not
      so effective to enhance the 131I absorption in the total body, as in the thyroid.
      No matter how the iodine concentration in the blood changed, the 1-week-old
      groups could not react to normalize the level. We drew standard curves, which
      enabled us to estimate the absorbed doses in the thyroid and the total body in
      the case of the injected activities of 131I for the newborn, pubertal and adult
      rats.

PMID- 11599882
TI  - Comet assay to assess the non-target effect of neutron-radiation in human
      peripheral blood.
AB  - The non-target effect of neutron-irradiation was assessed in unirradiated human
      peripheral blood lymphocytes using an alkaline comet assay. The isolated cells
      were incubated with an autologous plasma for 1 h at 37 degrees C before
      performing the assay. The cells exhibited a significant increase in the
      tailmoment when the irradiated blood (2 Gy, 570 keV neutron) was the source of
      plasma. The genotoxic effect lasted for 96 h when stored at -20 degrees C. It is
      believed to be mediated by the release of cytokines or other factors released by
      the irradiated cells. Plasma obtained from unirradiated blood or further
      irradiation of plasma did not enhance the tailmoment significantly. Thus, the
      adverse effect of neutron-exposure can be passed on to unirradiated neighbourhood
      through irradiated blood tissue without involving cell-cell contact. The non
      targeted radiation effect assumes greater consequences in radiotherapy and
      biodosimetry.

PMID- 11599883
TI  - A new image analysis system for biological dosimetry by fluorescent in situ
      hybridization. Step 1: metaphase finder and automatic metaphase acquisition
      validation.
AB  - Because of the large number of cells to be analyzed in cases of overexposure to
      ionizing radiation, an automated imaging system is desirable for scoring both
      translocations and dicentrics. This system should include three essential steps:
      automatic metaphase finding, automatic image capture at high magnification, and,
      finally, optimized data analysis for aberration interpretation. We evaluated a
      new image analysis system (CYTOGEN, IMSTAR, France) and found that its metaphase
      finder saved time, as much as quadrupling the speed of scoring chromosomal
      aberrations. Automatic metaphase selection did not appear to induce bias. We
      confirmed the equivalence of observing aberrations on a screen after automatic
      image capture and direct observation under a microscope. This work validated all
      of the steps necessary for obtaining images for automatic chromosomal aberration
      detection. The protocols for the detection of translocations may now be applied
      for biological dosimetry. This step will be validated in a future study.

PMID- 11599884
TI  - Radiosensitization by bromodeoxyuridine and hyperthermia: analysis of linear and
      quadratic parameters of radiation survival curves of two human tumor cell lines.
AB  - Sensitization by bromodeoxyuridine (BrdUrd) and hyperthermia (HT) on cell
      reproductive death induced by ionizing radiation was analyzed using the linear
      quadratic [S(D)/S(0)=exp(-(alphaD + betaD2)]] model. Plateau-phase human lung
      tumor cells (SW-1573) and human colorectal carcinonoma cells (RKO) were treated
      with BrdUrd, radiation and HT. LQ-analysis was performed at iso-incubation dose
      and at iso-incorporation level of BrdUrd. and at iso-HT doses and iso-survival
      levels after HT. Clonogenic assays were performed 24 h after treatment to allow
      repair of potentially lethal damage (PLD). In SW cells BrdUrd. HT or the
      combination significantly increased the alpha-parameter (factor 2.0-5.7), without
      altering the beta-parameter. In RKO cells sensitization with BrdUrd increased
      both a (factor 1.4) and beta (factor 1.3) while HT only influenced beta (factor
      2.1-4.0). The combination did not further increase the a and beta. The results
      indicate that BrdUrd has its main effect on the parameter alpha, dominant at
      clinically relevant radiation doses but that HT can affect both a and beta. The
      addition of BrdUrd and HT provides a method to enhance the efficacy of
      radiotherapy.

PMID- 11599885
TI  - OK-432 reduces mortality and bacterial translocation in irradiated and
      granulocyte-colony stimulating factor (G-CSF)-treated mice.
AB  - Bacterial translocation/Acute radiation syndrome/Endotoxin/G-CSF/OK-432 Acute
      radiation induces bacterial translocation from the gut, followed by systemic
      infection and sepsis. In order to reduce the mortality after acute whole body
      irradiation, it is essential to control bacterial translocation. In this study,
      we established a bacterial translocation assay as a sensitive method to detect
      minor mucosal injury by radiation. By utilizing this assay, we evaluated the
      adverse effects, if any, of hematopoietic reagents on the mucosal integrity in
      the respiratory and gastro-intestinal tracts. Bacterial translocation to the
      liver and spleen occurred after whole-body irradiation if the dose exceeded 6 Gy.
      The administration of G-CSF unexpectedly increased the bacterial translocation in
      8 Gy-irradiated mice. The pharmaceutical preparation of low-virulent
      Streptococcus pyogenes, OK-432, significantly reduced the endotoxin levels in
      peripheral blood without any reduction of bacterial translocation. A combined
      treatment with G-CSF and OK-432 decreased bacterial translocation and prevented
      death. This result indicates that the early administration of G-CSF has an
      adverse effect on bacterial translocation, and that a combined treatment of G-CSF
      and OK-432 attenuates the adverse effect of G-CSF and improves the survival rate
      after acute irradiation.

PMID- 11599886
TI  - Fas-independent apoptosis induced by UVC in p53-mutated human epithelial tumor
      A431 cells through activation of caspase-8 and JNK/SAPK.
AB  - A431 cells/UVC-induced apoptosis/Caspase 8/Fas/JNK/PAPK. We previously observed
      that p53-mutated human epithelial tumor A431 cells underwent apoptosis after
      ultraviolet C (UVC) irradiation through the caspases-8 and -3 pathway. Fas/FasL
      is known to initiate apoptosis in several cell lines via caspase-8 activation.
      Then, to determine if Fas/FasL mediates apoptosis in A431. we investigated Fas
      expression and modulation in UVC-irradiated A431 cells. A431 constitutively
      expressed Fas, which gradually decreased after UVC-irradiation. Pretreatment with
      a neutralizing anti-Fas antibody, ZB4, did not abrogate the UVC-induced
      apoptosis. An agonistic anti-Fas antibody, CH11, very slowly induced apoptosis in
      A431. suggesting that the constitutively expressed Fas had a low functional
      potential. Hence, UVC-induced apoptosis in A431 seems to occur independent of the
      Fas signal. Interestingly, however, a pretreatment with CH11 remarkably
      potentiated UVC-induced apoptosis. An inhibitor of caspase-8, Ac-IETD-CHO,
      partially inhibited UVC-induced apoptosis. JNK was phosphorylated immediately
      after exposure to UVC. prior to apoptotic chromatin condensation. Our data
      suggest that the activation of caspase-8 occurs independent of Fas upregulation,
      and that JNK/ SAPK contributes to UVC-induced apoptosis in human epithelial A431
      cells.

PMID- 11599887
TI  - Effect of a hypoxic radiosensitizer, AK 2123 (Sanazole), on yeast Saccharomyces
      cerevisiae.
AB  - Sanazole/DNA repair/Hypoxic radiosensitization/DNA polymerases/Saccharomyces
      cerevisiae Yeast Saccharomyces cerevisiae can exist in two physiological states,
      namely anaerobic and aerobic. They differ in their response to gamma- radiation
      and radiomodification. We report hereon our results concerning radiosensitization
      by Sanazole (AK-2123), a well-known hypoxic radio sensitizer, whose mechanism of
      action has been studied extensively. The results have revealed that Sanazole (1
      mM) when present during irradiation could specifically sensitize wild-type
      anaerobic yeast cells with a DMF of 2.4. In a radiation-sensitive mutant which
      lacks a DNA repair pathway specific for the recovery from gamma-radiation induced
      DNA damage, the extent of sensitization was considerably lower and the DMF was
      only 1.3. Studies on the liquid holding recovery of cells of both wild- type and
      rad52 yeast cells exposed to radiation in presence of Sanazole revealed that
      sensitization by Sanazole is due to a preferential increase in the DNA damage,
      and not by impairing DNA repair. This system thus holds promise for screening
      potential hypoxic chemical radiosensitizers.

PMID- 11599888
TI  - Sentinel node biopsy in head and neck cancer.
AB  - The purpose of this study was to assess the value of sentinel node (SN) biopsy in
      oral cancer by means of a lymphoscintigraphic technique and intraoperative
      detection by blue-dye combined with gamma-ray probe to facilitate identification
      of the SN. Forty-one T1-T2N0 patients underwent lymphoscintigraphy, SN biopsy,
      and modified radical neck dissection. An SN was identified in 39 of 41 patients
      by the combined use of intraoperative blue dye and the probe and was removed.
      Complete neck dissections were performed and the histological evaluation
      compared. Thirty-eight SNs in 35 patients were negative at final pathology and
      correctly predicted the pathological status of the specimens from the full-neck
      dissections. Five SNs in four patients had micrometastases and were the only
      metastatic nodes identified. The results of this study on a homogenous series of
      patients show that SN biopsy is a valuable staging technique in T1 and T2 oral
      cancer with uninvolved neck, provided that no previous surgery or radiotherapy
      has altered lymphatic drainage in the oral cavity or in the neck. In a large
      number of patients, SN biopsy can avoid unnecessary neck dissection and its
      relevant morphofunctional sequelae.

PMID- 11599889
TI  - Current practice and future directions in pathology and laboratory evaluation of
      the sentinel node.
AB  - We developed the techniques of lymphatic mapping and sentinel node (SN) biopsy to
      improve the management of patients with high-risk (thick and deep) primary
      melanoma. The SN is the first lymph node on the direct lymphatic drainage path
      from the primary tumor. This node is uniquely immune-modulated by the primary
      tumor and is the node most likely to contain the earliest stages of metastases.
      Accurate assessment of the SN requires careful evaluation of multiple sections
      removed from the areas of the node most likely to contain tumor. These sections
      are stained with hematoxylin and eosin and by immunohistochemistry with
      antibodies directed to tumor-associated markers (S-100, HMB-45, and Melan-A/MART
      1) in the case of melanoma and to cytokeratins for breast cancer. Studies are in
      progress to determine whether molecular biology techniques will detect additional
      nodes that contain truly occult tumor deposits.

PMID- 11599890
TI  - Molecular profiling of micrometastatic cancer cells.
AB  - Malignant tumors of epithelial tissue are the most common form of cancer and are
      responsible for the majority of cancer-related deaths in Western industrialized
      countries. As a result of progress in surgical treatment of these tumors,
      lethality is linked increasingly to early metastasis, which is generally occult
      at the time of primary diagnosis. For this reason, the direct identification of
      minimal residual cancer is of particular importance. The studies described below
      demonstrate the utility of immunocytochemical and molecular analysis in the
      diagnosis and characterization of minimal residual cancer. These methods not only
      can identify this critical stage of tumor progression but also may facilitate the
      development of therapies to prevent manifest metastasis.

PMID- 11599891
TI  - Lymphatic mapping and sentinel node lymphadenectomy for cancer: an overview.

PMID- 11599892
TI  - Lymphatic mapping and sentinel lymphadenectomy for melanoma: past, present, and
      future.
AB  - Intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) is a
      minimally invasive technique to determine whether a primary melanoma has
      metastasized to the sentinel node in the regional drainage basin. The sentinel
      node is the first node that receives lymph from any primary solid neoplasm whose
      drainage pattern is determined by its anatomical site and by the normal
      variations in lymphatic anatomy. Data from an ongoing multicenter phase III trial
      indicate that LM/SL for melanoma is accurate and reproducible when undertaken
      after a 30-case learning phase during which LM/SL is followed by complete
      lymphadenectomy. Although the optimal postoperative management of patients with
      sentinel node micrometastases identified by immunohistochemical staining has not
      been determined, adjuvant vaccine immunotherapy is a promising nontoxic approach
      that takes advantage of melanoma's intrinsic immunogenicity. Among the current
      adjuvant immunotherapy trials is a multicenter phase III study of CancerVax
      vaccine, an allogeneic polyvalent melanoma cell vaccine; results will indicate
      whether this vaccine should become standard therapy after complete surgical
      resection of melanoma metastatic to sentinel nodes.

PMID- 11599893
TI  - Molecular analysis in evaluating the sentinel node in malignant melanoma.
AB  - The most powerful predictor of cancer mortality in solid tumors is the status of
      regional lymph nodes. If the presence or absence of regional nodal metastases
      will determine which patient receives formal dissection or which patient enters
      adjuvant therapy, then a technique is needed to accurately screen lymph node
      samples for occult disease. Routine histopathologic examination commonly
      underestimates the number of patient with metastases. The use of reverse
      transcription-polymerase chain reaction (RT-PCR) method increased the detection
      of nodal metastases exponentially. Studies have shown that RT-PCR is a sensitive,
      reproducible, and efficient technique with prognostic significance. If
      identification of micrometastases through RT-PCR can lead to improved clinical
      outcome, then this more accurate method of staging would become the new standard
      in cancer care.

PMID- 11599894
TI  - Surgical and molecular approaches to the sentinel lymph nodes.
AB  - Intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) provides a
      unique opportunity for assessing potential immunologic interactions between the
      primary tumor and regional lymph node basin. We performed LM/SL in 24 patients
      with early-stage melanoma and resected an additional nonsentinel node (non-SN) in
      each case. Sentinel nodes (SNs) and non-SNs were evaluated by routine pathologic
      analysis, and a portion of each node was processed for expression of three
      dendritic markers of activation (CD80, CD86, CD40) and their corresponding T-cell
      receptors (CTLA-4 and CD28). Twenty (83%) patients had matched SNs and non-SNs. A
      total of 26 nodal pairs were obtained because one patient had three pairs and two
      other patients each had two pairs. Reverse transcriptase-polymerase chain
      reaction (RT-PCR) analyses of paired SNs and non-SNs demonstrated a marked
      reduction in semiquantitative expression of CD80 (77%), CD86 (77%), and CD40
      (85%), as well as CTLA-4 (88%) and CD28 (85%) in SNs. The diminished expression
      appeared to be unrelated to B-cell (CD20) and T-cell (CD2) expression. A
      quantitative reduction in dendritic cell markers in SNs may be important in the
      immunologic interaction between the primary site and regional lymph node basin
      and may also provide useful criteria for identifying SNs.

PMID- 11599895
TI  - Do patients with tumor-positive sentinel nodes constitute a homogeneous group?
AB  - From January 1993 to May 2000, 1062 patients with primary cutaneous melanoma and
      no evidence of clinically detectable regional node metastases underwent sentinel
      node (SN) dissection to microscopically define the tumor status of the regional
      lymph nodes. A total of 1165 biopsies were performed. The SN identification rate
      was 89.6%. In 62.2% of the cases, only one SN was detected; 26.4% of patients had
      two SNs; and 11.4% had three or more SNs. Analysis of survival indicated that the
      tumor status of the nodes was the most important prognostic factor. Breslow's
      thickness had a significant impact on survival in tumors 4 mm or thicker, and
      ulceration dropped to a borderline-significant P value. To assess the tumor
      burden in positive SNs, all slides for patients at the Istituto Nazionale Tumori
      and S. Pio X Hospital were reviewed. Of 658 patients in this series, 90 had
      positive SNs. Eighteen of these patients had evidence of metastasis in other
      nodes. Of the remaining 72 with a single tumor-involved SN, 62% had a single
      metastatic deposit. Preliminary data from this study indicate that several
      subgroups may be identified among patients with positive nodes, but adequate
      analysis of survival requires a larger number of patients and a multicenter
      study.

PMID- 11599896
TI  - The EORTC melanoma group translational research program on prognostic factors and
      ultrastaging in association with the adjuvant therapy trials in stage II and
      stage III melanoma. European Organization for Research and Treatment of Cancer.
AB  - Last year the Melanoma Group of the European Organization for Research and
      Treatment of Cancer (EORTC-MG) completed accrual (1418 patients) for trial EORTC
      18952, a three-arm phase III trial evaluating adjuvant therapy with two different
      intermediate doses of interferon (IFN) alfa-2b versus observation for stage IIB
      III melanoma. About 25% of the patients entered the trial with tumor-positive
      sentinel nodes (SNs). Prognosis was significantly better in SN-positive patients
      than in patients with palpable regional node involvement (P < .00001).
      Subsequently the EORTC-MG embarked on two large phase III trials of adjuvant
      therapy based on the tumor status of the SN. In trial EORTC 18961 for stage II
      melanoma, GM2-KLH/QS-21 vaccination is compared with observation (1300 patients);
      in trial EORTC 18991 for stage III melanoma, 5-year treatment with pegylated
      interferon alfa-2b (PEG-Intron) is compared with observation (900 patients).
      Translational research projects will compare SN assessment by hematoxylin and
      eosin (H&E) staining, immunohistochemistry (IHC), and reverse transcriptase
      polymerase chain reaction (RT-PCR) to determine the relative accuracy of each
      method and its correlation to relapse and survival of patients with stage II
      melanoma. In stage III patients, a similar workup of the most proximal
      nonsentinel node in the full lymph-node dissection specimen will indicate the
      accuracy of each methodology to detect nodal metastasis beyond the SN and the
      prognostic significance thereof. These findings will be correlated to the results
      of sequential blood testing by RT-PCR and by tumor marker assays for S100, TA90,
      and angiostatin. In addition, tumor-positive and tumor-negative SNs will be
      assessed for activated cytotoxic T lymphocytes and downregulation of dendritic
      cell functions.

PMID- 11599897
TI  - The Sunbelt Melanoma Trial.
AB  - The Sunbelt Melanoma Trial is a prospective randomized trial to evaluate the role
      of lymph node dissection and adjuvant interferon alfa-2b for patients with early
      lymph node metastases.

PMID- 11599898
TI  - The Sydney Melanoma Unit experience of sentinel lymphadenectomy for melanoma.
AB  - Commenced in 1992, a validation study involving 118 patients who underwent
      sentinel lymphadenectomy, then immediate complete regional node dissection,
      confirmed that the histological status of sentinel nodes (SNs) accurately
      reflects the status of regional nodes. Preoperative lymphoscintigraphy was found
      to be valuable in determining the number and position of SNs and demonstrated
      several previously unsuspected lymphatic drainage pathways. The greatest accuracy
      was achieved by using both blue dye and a gamma probe (to detect radioactivity in
      SNs after lymphoscintigraphy the previous day). In experience to date, SN
      positivity has been related to primary tumor thickness (<1.5 mm, 5%; 1.5-3 mm,
      14%; >3 mm, 24%). In 827 patients, with a median follow-up of 37 months,
      recurrence (at any site) has occurred in 47% of SN-positive patients but only 12%
      of SN-negative patients. Already 30% of SN-positive patients have died of
      melanoma, but only 6% of SN-negative patients. Although sentinel lymphadenectomy
      provides accurate staging and important prognostic information, its therapeutic
      significance has yet to be determined in clinical trials.

PMID- 11599899
TI  - The Augsburg experience: histological aspects and patient outcomes.
AB  - In Augsburg, sentinel lymphonodectomy (SLNE) was introduced into melanoma
      treatment in 1994. Diagnostic accuracy has been improved by early identification
      of sentinel lymph node (SLN) micrometastases and even more by their
      histomorphometric assessment. The S classification defines three categories of
      SLN metastases, S1 to S3, supplemented by S0 in the absence of metastasis. It is
      the leading predictor for the status of the remaining regional lymph nodes and an
      independent prognosticator for distant metastasis and survival. This should find
      consideration in adjuvant therapy trials. The pivotal question of whether SLN
      guided surgery itself achieves survival benefit has been approached by a follow
      up study that compared 387 SLNE-treated patients with 473 patients from the pre
      SLNE era. In contrast to nonsignificant differences in patients with thin and
      very thick primary tumors, death from intermediate-thickness melanoma (1.51 to 4
      mm) occurred significantly more often in the watch-and-wait group versus the SLNE
      group. These results must be validated by prospective randomized trials (e.g.,
      NCI 29605).

PMID- 11599900
TI  - Current status of sentinel lymphadenectomy in breast cancer.
AB  - Investigators at many cancer centers have verified that the sentinel node (SN) is
      the first lymph node to receive lymphatic drainage from a primary breast cancer
      and therefore the node most likely to contain metastatic tumor cells. When
      sentinel lymph node dissection (SLND) is undertaken by an experienced
      multidisciplinary team, the finding of a tumor-free SN almost invariably
      indicates that the patient has node-negative breast cancer and need not undergo
      further axillary dissection. At the present time, however, only centers with
      experience in SLND may abandon completion axillary lymphadenectomy when the SN is
      free of tumor. In other settings, level I and II axillary dissection is essential
      until the SLND team has achieved consistently accurate results and the
      institution has established excellent quality control.

PMID- 11599901
TI  - Histopathologic assessment of the sentinel lymph node in breast cancer.
AB  - Thorough pathologic examination of the sentinel lymph node (SLN) improves the
      accuracy of breast cancer staging and reduces the rate of false-negative results.
      Intraoperative examination of the SLN with cytological or frozen section
      techniques remains problematic. Diagnostic difficulties encountered on
      hematoxylin and eosin paraffin sections in general are easily resolved with
      cytokeratin immunohistochemistry, but the finding of minute metastases may lead
      to diagnostic and therapeutic dilemmas. Pathologic characteristics of the primary
      tumor and SLN metastasis determine the risk of non-SLN metastasis in the same
      lymphatic basin.

PMID- 11599902
TI  - Nuclear medicine in the detection of the sentinel node.
AB  - Lymphoscintigraphy and radioguided surgery are valuable tools for contemporary
      surgical staging of malignancies, but they require attention to detail and a
      moderate level of experience for optimal clinical use. Wide use of these
      procedures has demonstrated that the methodology can be learned with guidance
      from a few dozen cases. Their accurate use significantly enhances the sentinel
      node technique.

PMID- 11599903
TI  - Occult metastases in patients with breast cancer.
AB  - The presence of occult metastases in the lymph nodes, bone marrow, or both of
      these compartments may not only define patients who are at higher risk for
      recurrence and death but also may identify biologically distinct mechanisms of
      tumor spread (e.g., lymphatic vs. vascular dissemination). Use of techniques to
      detect occult metastases may also allow the identification of a biologically
      important population of cells, i.e., those cells constituting the earliest
      metastatic population of tumor cells. Thus, techniques that identify occult
      metastases may be valuable in furthering our understanding of the events
      regulating tumor dissemination.

PMID- 11599904
TI  - Blue versus hot: learning the techniques with dye and isotopes.
AB  - Intraoperative lymphatic mapping and sentinel node (SN) biopsy has generated a
      tremendous amount of interest in the field of surgical oncology since its
      introduction for patients with early-stage melanoma. The SN concept has been
      applied recently to many solid tumors, including melanoma, breast cancer, thyroid
      cancer, gynecological malignancies, and colorectal cancers. Although the concept
      of intraoperative lymphatic mapping and SN biopsy has been validated in multiple
      single-institution studies as well as multicenter trials, there is still much
      discussion as to which mapping technique is easier to learn. This article focuses
      on the technical aspects of SN mapping in breast cancer and reviews the most
      recent data to try to determine which technique is superior.

PMID- 11599905
TI  - Lymphatic mapping in breast cancer: combination technique.
AB  - The current standard of care for patients with invasive breast cancer is complete
      removal of the tumor by mastectomy or lumpectomy, with documentation of negative
      margins, followed by complete axillary dissection. Our group has examined the
      efficacy of lymphatic mapping of the sentinel node via the combination technique
      in 594 patients with breast cancer. A radiocolloid was injected at six
      intraparenchymal locations surrounding the tumor 2 hours prior to the operation.
      A 1% solution of isosulfan blue dye was injected into the breast just before
      prepping the patient. The breast was compressed and massaged for 5 minutes. The
      surgical and pathological data were prospectively collected. Lymphatic mapping of
      the sentinel node with a combination of blue dye and radiocolloid enhanced preop
      localization, operation efficiency, internal mammary node detection, and
      quantitative measure of detection. The combined technique also significantly
      reduced the learning curve for achieving proficiency.

PMID- 11599906
TI  - Lymphatics of the breast and the rationale for different injection techniques.
AB  - Recent studies suggest that the sentinel lymph node in the axilla can be
      identified no matter where the tracer is administered in the breast. Tracers
      injected in the skin or subareolar plexus may be the quickest to travel to the
      axilla but rarely identify sentinel nodes outside the axilla. Tracers
      administered in or around the tumor identify sentinel nodes in the axilla but
      also in the internal mammary chain, in the breast parenchyma, in between the
      pectoralis muscles, and in the supraclavicular fossa. Extra-axillary sentinel
      nodes can be seen in approximately 25% of the patients. Administration of the
      tracer in the breast parenchyma with pursuit of sentinel nodes both in the axilla
      and elsewhere provides more accurate staging in addition to preventing
      unnecessary axillary node dissections. This will lead to more accurate
      indications for both postoperative radiotherapy and adjuvant systemic treatment.
      Implications for the staging system should be considered as well.

PMID- 11599907
TI  - Is axillary dissection necessary after positive sentinel node biopsy? Yes!
AB  - Axillary dissection has been considered a staging procedure in recent years.
      Sentinel node biopsy can accurately stage a patient as node-positive or node
      negative, raising questions about the need for completion dissection when the
      sentinel node is positive. This article summarizes data indicating that
      approximately 50% of patients with sentinel node metastasis have additional
      positive nodes. For these women, completion axillary dissection provides
      prognostic information, maintains local control, and may have a survival benefit.
      Until definitive data from the American College of Surgeons Z11 study is
      available, completion dissection should remain standard practice.

PMID- 11599908
TI  - Sentinel node dissection in early-stage breast cancer: ongoing prospective
      randomized trials in the USA.
AB  - One of the most important advances in the surgical treatment of early-stage
      breast cancer has been the introduction of sentinel lymph node dissection as an
      alternative to routine axillary node dissection. This minimally invasive
      procedure may reduce the morbidity of surgical treatment and improve staging of
      the axillary lymph node basin. Over the last 5 to 7 years, numerous institutions
      have published their sentinel node identification rates, false-negative events,
      optimal techniques, and learning curves. Many of these issues need confirmation
      in a prospective multicentered fashion and other issues such as survival and
      comparative toxicities require prospective randomized trials. Two prospective
      randomized trials using sentinel node biopsy have been implemented in the United
      States: the NSABP B-32 trial and the ACOSOG Z0010/Z0011 trials. Design,
      hypotheses, and rationale for these trials are discussed.

PMID- 11599909
TI  - Aberrant drainage and missed micrometastases: the value of lymphatic mapping and
      focused analysis of sentinel lymph nodes in gastrointestinal neoplasms.
AB  - Lymph node analysis is essential for staging gastrointestinal (GI) neoplasms. Our
      group has conducted several studies of intraoperative lymphatic mapping and
      sentinel lymphadenectomy (LM/SL) for the staging of GI neoplasms. LM is performed
      following injection of 0.5-1 ml of isosulfan blue dye, and blue-stained sentinel
      lymph nodes (SLNs) are analyzed by hematoxylin and eosin (H&E) staining, multiple
      sectioning, and cytokeratin immunohistochemistry. In feasibility trials, LM
      identified at least one SLN in 121 of 126 patients. Of the 58 cases with nodal
      metastasis, 50 (89%) had at least one positive SLN and 24 (42%) had nodal
      metastasis only in the SLN. In 25 cases, tumor deposits were identified by
      multiple sectioning (n = 8) or immunohistochemistry (n = 17) only. In 10 cases
      (8%), LM identified aberrant lymphatic drainage that altered the extent of the
      lymphadenectomy. Our cumulative experience indicates that focused analysis of the
      SLNs draining GI neoplasms can increase the detection of micrometastases and may
      improve selection of patients for adjuvant treatment.

PMID- 11599910
TI  - Laparoscopic detection of sentinel lymph nodes in gastrointestinal cancer: a
      novel and minimally invasive approach.
AB  - Although the sentinel node (SN) concept has been validated in malignant melanoma
      and breast cancer, the application of this concept for other solid tumors,
      including gastrointestinal (GI) cancer, is still controversial. We have
      demonstrated the feasibility of radioguided SN mapping during laparotomy in
      patients with esophageal, gastric, and colorectal cancers. In 188 patients, the
      SNs identified by this technique had an overall diagnostic accuracy of 96% for
      regional lymph node metastasis. Aberrant drainage sites that have been called
      skip metastasis from the primary lesion were detectable using this method. More
      recently, we have undertaken SN mapping during laparoscopic surgery. A
      combination of radiotracer and blue dye optimized the identification of SNs that
      drained GI cancers. Our preliminary data indicate that laparoscopic mapping of
      the SN is a sensitive intraoperative technique for identifying lymph node
      micrometastasis, and we believe that it will become an important component of a
      minimally invasive approach to early-stage GI cancers.

PMID- 11599911
TI  - Can sentinel node navigation surgery reduce the extent of lymph node dissection
      in gastric cancer?
AB  - Our group has conducted several studies of sentinel node navigation surgery
      (SNNS) for the management of early gastric cancer. To determine the distribution
      of nodal metastases and micrometastases, we used immunohistochemical staining
      with anticytokeratin antibody to examine 2605 lymph nodes obtained from 108
      consecutive patients with submucosal gastric cancer. When nodes were negative by
      routine hematoxylin and eosin (H&E) examination, micrometastases were confined to
      one regional lymphatic pathway near the primary tumor; however, when nodes were
      H&E-positive, micrometastases were distributed more widely. The wide and
      complicated lymphatic stream from a gastric tumor contributed to the relatively
      high (23%) incidence of micrometastases and the frequent occurrence of skip
      metastasis. In another study, we used a combination of blue dye and
      radiopharmaceutical to perform SNNS in 18 patients with early gastric cancer. The
      rate of sentinel node detection was 94%, and the average number of sentinel nodes
      per patient was three. Technical issues included size of particles, method of
      injection, accuracy of frozen section examination, and standard criteria for
      defining a sentinel node. SNNS for gastric cancer is a promising technique;
      further study of various anatomic and pathologic factors will indicate whether it
      can be used to determine the extent of lymphadenectomy necessary in patients with
      early gastric cancer.

PMID- 11599912
TI  - Ultrastaging of colorectal cancer by sentinel lymph node mapping technique--a
      multicenter trial.
AB  - Sentinel lymph node (SLN) mapping accurately diagnoses the status of nodal basin
      with >95% accuracy in melanoma and breast cancer. A multicenter trial for SLN
      mapping was performed on 203 patients with colorectal cancer to determine
      accuracy, upstaging, skip metastasis, and aberrant drainage. Lymphazurin 1% was
      injected subserosally around the tumor and 1-4 blue staining nodes were marked as
      SLNs for detailed histological analysis. SLN mapping was successful in 98% of
      patients with an average of 1.7 SLNs per patient. SLNs were negative in 63% of
      the patients and positive in 37% of the patients. Skip metastasis was seen in 8
      of the patients. Occult micrometastasis was found in 14% of patients. In 5% of
      the patients, unusual lymphatic drainage lead to an alteration of the extent of
      lymphadenectomy. This multicenter trial proved that SLN mapping in patients with
      colorectal cancer is simple, cost effective, and upstages at least 14% of
      patients from AJCC stage I/II to stage III. These patients may then benefit from
      adjuvant chemotherapy.

PMID- 11599913
TI  - Merkel cell carcinoma.
AB  - Merkel cell carcinoma is an unusual cutaneous malignancy with a propensity for
      spreading to regional lymph nodes, either at presentation or as a first site of
      relapse. Complete surgical resection is the mainstay of treatment of the primary
      tumor. Because the nodotrophic behavior of the tumor is recognized, lymphatic
      mapping with sentinel lymph node biopsy is becoming increasingly popular in the
      initial surgical staging of these patients. The role of elective lymphadenectomy
      in patients with clinically negative regional nodal basins is unknown. The role
      of adjuvant radiotherapy, either to the primary site or regional nodal basin,
      remains undefined. The role of adjuvant chemotherapy in diminishing the risk of
      subsequent systemic recurrence in patients with positive nodes remains undefined.
      Overall response rates to combination chemotherapy for surgically unresectable
      distant metastatic disease are generally high, although responses are transient.

PMID- 11599914
TI  - Optimal nuclear medicine support in sentinel node detection.
AB  - The correct identification of sentinel lymph nodes (SLNs) is paramount if this
      technique is to become the standard of care in the management of early disease in
      surgical oncology. Despite the apparent attraction and ease of this approach, a
      detailed understanding of its different technical components is vital. High
      sensitivity, reproducibility, and accuracy levels must be achieved in the
      identification and discrimination of the SLN if the extent and place of the
      standard lymph node diagnostic dissections can be challenged. This article
      reviews the technology and methodology and gives indications of the possible
      progress to be achieved.

PMID- 11599915
TI  - Detection of lipoprotein(a) in intraparenchymal cerebral vessels: correlation
      with vascular pathology and clinical history.
AB  - Serum levels of lipoprotein(a), Lp(a), have been shown to be associated with
      increased risk of atherosclerosis (AS) and AS-related diseases such as myocardial
      and ischemic cerebral infarcts (ICI). Lp(a) has been detected in the vascular
      wall of the aorta and coronary vessels, and we documented the presence of apo(a)
      in cerebral vessels of the Circle of Willis, associated with AS changes. In this
      study we further investigated and characterized the biochemical nature of Lp(a)
      detected in both large and small cerebral parenchymal vessels. Autopsy specimens
      of cerebral vessels of 51 patients were examined by immunohistochemistry with
      monoclonal antibodies against apo(a), apoB, and plasminogen. Lp(a) was detected
      in cerebral capillaries and arterioles. All of the 8 patients with ICI expressed
      Lp(a) in parenchymal vessels, generally (6/8) in both capillaries and arterioles.
      Of 43 patients without ICI only 25 had Lp(a) detected. Among the patients without
      ICI, there was a slightly increased incidence of parenchymal Lp(a) in those
      patients who had severe hypoxic brain damage (12/20) compared to those patients
      without severe hypoxic damage (9/23). Thus, the presence of Lp(a) in small
      cerebral parenchymal vessels may reflect the role of Lp(a) in ICI.

PMID- 11599916
TI  - Identification of TNF-alpha-sensitive sites in HCMVie1 promoter.
AB  - Viral vectors using the human cytomegalovirus immediate-early promoter (HCMVie1
      promoter) are potentially efficient tools for gene delivery in vivo to diverse
      cell types. We previously demonstrated that two cytokines, tumor necrosis factor
      alpha (TNF-alpha) and interferon-gamma (INF-gamma), inhibited transgene
      expression from this promoter in skeletal and cardiac myocytes. In this study,
      electrophoretic mobility shift assays (EMSAs) were performed to identify the TNF
      alpha response elements from the HCMVie1 promoter. The results show that TNF
      alpha enhances the interaction of nuclear proteins from the C2C12 myocyte line
      with a single restricted segment of the HCMVie1 promoter. In vitro DNase I
      footprinting defined precisely the sites of interaction to two elements:
      nucleotides -1 to 0 and +24 to +36 relative to a transcription initiation cap
      homologous in the HCMVie1 promoter. These sites contain homologous sequences for
      cap initiation site (82%) and NFkappaB (62%) sites, respectively. Specificity was
      further ascertained by competitive EMSAs with wild-type and mutant
      oligonucleotide probes. Southwestern blotting showed that three proteins (45, 30,
      and 20 kDa) bound to this TNF-alpha-sensitive element, separately. However, EMSAs
      failed to prove a role for Yin Yang-1 (YY-1), NFkappaB (p65), or NFkappaB (p50)
      in binding to these sites. Our results provide evidence for two novel sites in
      the HCMVie1 promoter that are targets for TNF-alpha enhanced binding of
      transcription factors.

PMID- 11599917
TI  - Regulation of the association between PSTPIP and CD2 in murine T cells.
AB  - Prominent in T cells and natural killer cells, CD2 binding protein 1 (CD2BP1)
      plays an important role in CD2-mediated adhesion and signal transduction. In the
      current study, we investigated CD2 and PSTPIP (proline, serine, threonine
      phosphatase interacting protein, murine homologue of CD2BP1) interactions in
      purified mouse splenic T cells. PSTPIP associated with CD2 in both resting and
      activated T cells. Following various stimuli, such as concanavalin A, anti
      TCRbeta, anti-CD3epsilon, anti-CD3epsilon/phorbol myristate acetate (PMA), IL-2,
      or PMA/ionomycin, PSTPIP and CD2 expression, as well as their association,
      increased in a time-dependent fashion. While PSTPIP expression and CD2 expression
      were comparable across most groups, the PSTPIP-CD2 association stimulated by anti
      CD3epsilon alone was significantly greater than with other stimuli. Stimulation
      by anti-CD3epsilon plus anti-CD28 induced even greater PSTPIP-CD2 association
      than anti-CD3epsilon treatment alone, indicating that CD28 initiated signals are
      involved in regulating this interaction. There was no direct association between
      CD3epsilon or CD28 and PSTPIP. Tyrosine phosphorylated PSTPIP bound poorly to CD2
      compared to dephosphorylated PSTPIP, and protein tyrosine phosphatase was shown
      to affect both phosphorylation of PSTPIP and the CD2-PSTPIP association. In
      addition to CD2, PSTPIP associated with CD4, CD8, CD54, and CD62L. CD2 and CD4
      ligation reciprocally regulated their association with PSTPIP. These findings
      indicate that T cell activation, particularly through the CD3 and CD28 signal
      transduction pathways, regulates PSTPIP-CD2 interactions. PSTPIP likely has
      additional broader effects through interactions with CD4, CD8, CD54, and CD62L,
      and this may influence T cell responses to antigen.

PMID- 11599918
TI  - Effect of abdominal surgery on the activity of acid and alkaline ribonucleases in
      rats.
AB  - Ribonucleases (RNases) are a group of enzymes that hydrolyze different classes of
      RNA. It has been suggested that RNase activity in cells can act to indirectly
      regulate protein synthesis by controlling RNA degradation. However, little is
      known about the role of RNases under conditions characterized by a sudden
      increase of protein synthesis, such as with surgical trauma. The aim of this
      study was to investigate the effect of abdominal surgery on acid and alkaline
      RNase activities in rat liver. Acid and alkaline RNase activities decreased
      significantly at 3 h after surgery, reaching the lowest level at 16 h (63% less
      than control) for the acid and 6 h (39% less than control) for the alkaline
      activities. Acid RNase activity returned to its initial values 20 h after
      surgery, while alkaline RNase activity remained decreased even 24 h after
      surgery. In order to determine whether the observed decreases in RNase activity
      were produced by RNase inhibitors (RIs), the enzymatic activities of both RNases
      were measured after the addition of zinc, to dissociate possible RI/RNase
      complexes. Zinc addition increased acid RNase activity by 61%, but had no
      significant effect on alkaline RNase activity. Administration of cycloheximide
      (an inhibitor of protein synthesis) 2 h before surgery prevented the decrease of
      acid RNase activity 12 h after surgery, while there was no effect on the decrease
      in alkaline RNase activity. These results show that surgery produces a decrease
      in hepatic acid and alkaline RNase activities. The decreased acid RNase activity
      could be a consequence of the de novo synthesis of RNase inhibitors as a response
      to surgical trauma, while the mechanism involved in the decrease of alkaline
      RNase activity is unclear. Under pathophysiological conditions, which induce a
      high rate of protein synthesis, such as surgical wounding, decreased acid and
      alkaline RNase activity could provide an important mechanism for enhanced protein
      synthesis, by prolonging RNA half-life.

PMID- 11599919
TI  - Oral low-carbohydrate alcohol liquid diet induces experimental steatohepatitis in
      the rat.
AB  - The intragastric tube feeding model of alcoholic liver disease in the rat induces
      significant liver histopathology, including steatohepatitis and fibrosis. The
      question is, if the same low-carbohydrate diet is fed ad lib, will the same
      pathology develop? Rats were fed a liquid diet with ethanol ad lib that was low
      in calories derived from carbohydrates for 2 months. The urinary ethanol levels
      (UALs) were monitored at hourly, daily, and weekly intervals, and the growth of
      the rats was charted. The liver histopathology and blood transaminase levels were
      determined. Rats fed ethanol grew 1 g/day, which was 2 g/day less than when they
      were fed the same diet intragastrically. UALs varied hourly between 150 and 500
      mg%, daily between 120 and 360 mg%, and weekly between 0 and 500 mg%. Individual
      rat UALs showed no predictable pattern. The pair-fed controls ate all of their
      daily ration within 12 h, then fasted until the next day. The histopathology and
      blood alanine aminotransferase were similar to those seen with the intragastric
      tube feeding of the same diet, except that necrosis, inflammation, and fibrosis
      did not develop. The conclusion was that the oral feeding of a low-carbohydrate
      diet produces less liver injury than that produced by the same diet fed
      intragastrically. The UALs varied hourly, daily, and weekly in individual rats,
      making it difficult to synchronize UALs at the time of sacrifice.

PMID- 11599920
TI  - "Piecemeal" necrosis: renamed troxis necrosis.
AB  - Piecemeal necrosis, currently called interface hepatitis, is a feature of viral
      hepatitis as well as autoimmune hepatitis and steatohepatitis. The mechanism of
      liver cell loss and piecemeal necrosis needs to be determined. We hypothesize
      that piecemeal necrosis in hepatitis is due to a piecemeal removal of hepatocyte
      cytoplasm by lymphocytic ingestion. To test this hypothesis, 61 consecutive liver
      biopsies were examined by light microscopy, by immunohistochemistry and by
      electron microscopy, and the lymphocytic-hepatocytic interaction was
      morphologically assessed. In cases of hepatitis C, hepatitis B, autoimmune
      hepatitis, primary biliary cirrhosis, and steatohepatitis, piecemeal necrosis was
      found. Using cytokeratin stains, it was apparent that the lymphocyte-hepatocyte
      interaction and piecemeal necrosis leads first to binding of the lymphocyte to
      hepatocyte plasma membrane and then blebbing or indentation of the hepatocyte by
      the lymphocyte, followed by endocytosis of liver cell cellular components and
      digestion in the lymphocyte lysosomes. This process is repeated while the
      cytoplasm and the nucleus of the hepatocyte disappear bite by bite, and only
      nubbins of residual hepatocytic cytoplasm remain, either attached to intact
      hepatocytes or surrounded and sequestered within scar tissue and lymphocytes. We
      conclude that piecemeal necrosis is a gradual disappearance of hepatocytes as a
      result of lymphocyte-hepatocyte binding and ligand internalization of liver
      surface molecules by the lymphocyte. This gradual process leads to a slow
      reduction of hepatocyte size and eventual disappearance at the interface between
      the lobule and portal tracts. To term this new kind of necrosis, we propose the
      name troxis necrosis, after the Greek noun meaning "nibbling."

PMID- 11599921
TI  - Differences in alpha smooth muscle actin expression between fibroblasts derived
      from Dupuytren's nodules or cords.
AB  - Dupuytren's contracture is a fibrotic lesion of the palmar fascia that includes
      two distinct structures, the nodule and the cord. Histologically the Dupuytren's
      nodule has a high cell density with numerous myofibroblasts (alpha smooth muscle
      actin-expressing fibroblasts). The Dupuytren's cord has a rich connective tissue
      matrix containing a low density of elongated spindle-shaped fibroblasts. The
      cytoskeletal structures of cultured fibroblasts derived from Dupuytren's nodules
      and cords of surgically treated patients were studied and compared.
      Immunohistology showed no obvious morphological differences between Dupuytren's
      nodule and cord cultured cells, when focal adhesions (vinculin), intermediate
      filaments (vimentin), microtubules (alpha tubulin), or microfilaments
      (filamentous actin) were viewed. However, a greater proportion of nodule cultured
      cells were positive for alpha smooth muscle actin compared to cord-derived cells.
      The increased expression in nodule cells of alpha smooth muscle actin was
      confirmed by Western blot analysis. It appears that fibroblasts derived from
      Dupuytren's nodules or cords retain in vivo cytoskeletal characteristics, when
      grown in tissue culture.

PMID- 11599922
TI  - Tissue-specific regulation of Chk1 expression by p53.
AB  - The regulation of Chk1, a critical protein kinase involved in G(2) phase arrest,
      has been a subject of recent research. Chk1 phosphorylates tumor suppressor p53
      at multiple sites, while p53 has been shown to downregulate Chk1 expression under
      stress conditions in vitro, suggesting negative feedback between the two
      checkpoint proteins. Using the p53 knockout mouse model, we demonstrate by
      Western blot and immunohistochemistry that mChk1 expression is induced in spleen,
      thymus, and dermal fibroblasts and is reduced in lung and testis in p53(-/-) mice
      compared to p53(+/+) controls. The mChk1 protein was undetectable in heart,
      kidney, and skin, whereas abundant expression was observed in brain and liver in
      both p53(+/+) and p53(-/-) mice. These data indicate that p53 regulates Chk1
      expression in a tissue-specific manner.

PMID- 11599923
TI  - Strain-dependent differences in the pattern of aortic lipid deposition in
      cholesterol-fed rabbits.
AB  - Spontaneous lesions develop downstream of branch points in immature human and
      rabbit aortas, but occur more frequently at the sides and upstream of these sites
      in mature vessels. Cholesterol-induced lesions in mature rabbits, however, have
      shown the downstream distribution in one trial and the more upstream distribution
      in another. We tested the hypothesis that this discrepancy reflected a difference
      in the degree of impairment of the nitric oxide pathway. Mature rabbits were fed
      cholesterol-enhanced versions of the two base diets used in the previous trials,
      and some were given additional vitamin E or l-arginine to protect the NO pathway
      or L-NAME to inhibit it. Unexpectedly, the rabbits developed a lesion pattern
      intermediate between the two previously described, and this distribution was
      unaffected by the base diet or supplements. Consequently, an exploratory study
      was conducted to investigate possible effects of other differences between the
      two earlier trials. These were the precise age of the mature rabbits and the
      feeding protocol employed; both base diets again were used. Two different lesion
      patterns were observed in this trial, but there was no systematic effect of any
      of the controlled variables. Instead, there appeared to be an influence of the
      supplier from which the rabbits had been obtained. A multivariate analysis of all
      four trials confirmed that the pattern of disease was associated with rabbit
      strain, and not with base diet, cholesterol level, or precise age.

PMID- 11599924
TI  - The nude mouse skin phenotype: the role of Foxn1 in hair follicle development and
      cycling.
AB  - The original nude mouse mutation has proven to be an incredibly valuable
      biomedical tool since its discovery in 1966. Initially its value was as a tool to
      study the immune system. The immunodeficiency in this mutant mouse made nude mice
      valuable as hosts for xenografts, primarily for cancer research. More recently,
      the most obvious clinical feature of this mutant mouse, lack of hair, has been
      capitalized on to define the role of Foxn1 in normal and pathological skin and
      hair follicle physiology.

PMID- 11599925
TI  - Morphology of Australopithecus anamensis from Kanapoi and Allia Bay, Kenya.
AB  - The hominid species Australopithecus anamensis was originally described in 1995,
      with new specimens and more secure dates given in 1998. This paper lists all
      fossils attributed to A. anamensis, and provides anatomical descriptions of those
      not yet described in detail with photographs of all but undiagnostic fragments.
      We also provide comparative analysis of these specimens. The A. anamensis
      holotype mandible was found at Kanapoi, as were most of the paratypes. The Allia
      Bay sample is less well represented, and does not preserve many anatomical
      elements diagnostic of this species. Still, the Allia Bay sample most closely
      resembles that from Kanapoi, and we suggest that for the time being it be
      retained as A. anamensis. A. anamensis most closely resembles A. afarensis, but
      can be distinguished from it in many features. Most of these features are
      inferred to be primitive for the genus. Based on the limited postcranial evidence
      available, A. anamensis appears to have been habitually bipedal, although it
      retained some primitive features of its upper limbs. A. anamensis differs from A.
      afarensis in having narrower, more parallel jaws with a very slightly more ape
      like canine/premolar complex than is found in A. afarensis, although not as ape
      like as in Ardipithecus ramidus. It had slightly larger lower lateral incisors, a
      unique upper canine morphology, and a different structure of the lateral nasal
      aperture than A. afarensis. A. anamensis had at least as great a range of body
      size, and perhaps slightly greater canine dimorphism, although this is difficult
      to determine. At present, there appears to be no autapomorphies precluding A.
      anamensis from ancestry of A. afarensis.

PMID- 11599926
TI  - Molecular mechanism of hydrogen peroxide conversion and activation by Cu(II)
      amikacin complexes.
AB  - The interactions between Cu(II)-amikacin complexes [Cu(II)-Ami] and hydrogen
      peroxide were studied by spectroscopy (EPR, UV-vis, CD, XAS) and cyclic
      voltammetry. A monomer-dimer equilibrium was detected at complex concentrations
      above 5 mM (log K(dim) = 1.84 +/- 0.03). The dimeric complex undergoes easy,
      although irreversible oxidation (ca. 0.5-0.6 V) to a Cu(III) species on platinum
      electrode. However, the monomeric complexes are able to catalyze hydrogen
      peroxide disproportionation reaction at pH 7.4 in a multistep process, mediated
      by hydroxyl radicals and involving both Cu(I)/Cu(II) and Cu(II)/Cu(III) redox
      pairs.

PMID- 11599927
TI  - HPLC/1H NMR spectroscopic studies of the reactive alpha-1-O-acyl isomer formed
      during acyl migration of S-naproxen beta-1-O-acyl glucuronide.
AB  - A widely held view in drug metabolism and pharmacokinetic studies is that the
      initial 1-isomer to 2-isomer step in the intramolecular acyl migration of drug
      ester glucuronides is irreversible, and that alpha-1-O-acyl isomers do not occur
      under physiological conditions. We investigated this hypothesis using high
      performance liquid chromatography directly coupled to proton nuclear magnetic
      resonance spectroscopy (HPLC/1H NMR) and mass spectrometry (LC/MS) to probe the
      migration reactions of S-naproxen beta-1-O-acyl glucuronide, in phosphate buffer
      at pH 7.4, 37 degrees C. We report the first direct observation of the alpha-1-O
      acyl isomer of a drug ester glucuronide (S-naproxen) formed in a biosystem via
      the facile acyl migration of the corresponding pure beta-1-O-acyl glucuronide.
      The unequivocal identification of the reactive product was achieved using stopped
      flow one-dimensional HPLC/1H NMR and two-dimensional 1H-1H total correlation
      spectroscopy (1H-1H TOCSY). Parallel LC/ion-trap mass spectrometry yielded the
      confirmatory glucuronide masses. Moreover, "dynamic" stopped-flow HPLC/1H NMR
      experiments revealed transacylation of the isolated alpha-1-O-acyl isomer to a
      mixture of alpha/beta-2-O-acyl isomers; the reverse reaction from the isolated
      alpha/beta-2-O-acyl isomers to the alpha-1-O-acyl isomer was also clearly
      demonstrated. This application of "dynamic" stopped-flow HPLC/1H NMR allows key
      kinetic data to be obtained on a reactive metabolite that would otherwise be
      difficult to follow by conventional HPLC and NMR methods where sample preparation
      and off-line separations are necessary. These data challenge the widely held view
      that the alpha-1-O-acyl isomers of drug ester glucuronides do not occur under
      physiological conditions. Furthermore, the similar formation of alpha-1-O-acyl
      isomers from zomepirac and diflunisal beta-1-O-acyl glucuronides has recently
      been confirmed (Corcoran et al., unpublished results). Such reactions are also
      likely to be widespread for other drugs that form ester glucuronides in
      biological systems. Ultimately, the presence of significant quantities of the
      kinetically labile alpha-1-O-acyl glucuronide isomer may also have toxicological
      implications in terms of reactivity toward cellular proteins.

PMID- 11599928
TI  - Role of free radicals in the toxicity of airborne fine particulate matter.
AB  - Exposure to airborne fine particles (PM2.5) is implicated in excess of 50 000
      yearly deaths in the USA as well as a number of chronic respiratory illnesses.
      Despite intense interest in the toxicity of PM2.5, the mechanisms by which it
      causes illnesses are poorly understood. Since the principal source of airborne
      fine particles is combustion and combustion sources generate free radicals, we
      suspected that PM2.5 may contain radicals. Using electron paramagnetic resonance
      (EPR), we examined samples of PM2.5 and found large quantities of radicals with
      characteristics similar to semiquinone radicals. Semiquinone radicals are known
      to undergo redox cycling and ultimately produce biologically damaging hydroxyl
      radicals. Aqueous extracts of PM2.5 samples induced damage to DNA in human cells
      and supercoiled phage DNA. PM2.5-mediated DNA damage was abolished by superoxide
      dismutase, catalase, and deferoxamine, implicating superoxide radical, hydrogen
      peroxide, and the hydroxyl radical in the reactions inducing DNA damage.

PMID- 11599929
TI  - Prediction of the acute toxicity (96-h LC50) of organic compounds to the fathead
      minnow (Pimephales promelas) using a group contribution method.
AB  - A group contribution method has been developed to correlate the acute toxicity
      (96-h LC50) to the fathead minnow (Pimephales promelas) for 397 organic
      chemicals. Multilinear regression and computational neural networks (CNNs) were
      used for model building. The models were able to achieve a fairly good
      correlation of the data (r2 > 0.9). The linear model, which included four
      specific interaction terms, provided a rapid means of predicting the toxicity of
      a compound. The CNN model was able to yield virtually the same predictions with
      or without the four interaction terms that were included in the multilinear
      model.

PMID- 11599930
TI  - Coumarin metabolism by rat esophageal microsomes and cytochrome P450 2A3.
AB  - The rat esophagus is strikingly sensitive to tumor induction by nitrosamines, and
      it has been hypothesized that this tissue contains cytochrome P450 enzymes
      (P450s) which catalyze the metabolic activation of these carcinogens. The
      metabolic capacity of the esophagus is not well characterized. In the study
      described here, the products of 14C-coumarin metabolism by rat esophageal
      microsomes were identified and quantified. Metabolite characterization was by
      LC/MS/MS and GC/MS and comparison to standards, quantification was by radioflow
      HPLC. The coumarin metabolites formed by rat esophageal microsomes were compared
      to those formed by P450 2A3. The major metabolites formed by esophageal
      microsomes were 8-hydroxycoumarin, o-hydroxyphenylacetaldehyde (o-HPA), and o
      hydroxyphenylacetic acid (o-HPAA). A smaller amount of 5-hydroxycoumarin, about
      one-third the 8-hydroxycoumarin, was also formed. o-HPA and o-HPAA are products
      of coumarin 3,4-epoxidation. The relative rates of coumarin 8-hydroxylation and
      3,4-epoxidation were similar. Coumarin 8-hydroxylation has not previously been
      reported as a major pathway in any tissue, and no P450s have yet been reported to
      catalyze this reaction. P450 2A3 catalyzed both the 7-hydroxylation and 3,4
      epoxidation of coumarin. P450 2A3 was previously characterized as a coumarin 7
      hydroxylase, however, in this study, we report that it catalyzes the formation of
      o-HPA more efficiently. The Km and Vmax were 1.3 +/- 0.35 microM and 0.65 +/-
      0.06 nmol/min/nmol P450 for coumarin 7-hydroxylation and 1.4 +/- 0.58 microM and
      3.1 +/- 0.46 nmol/min/nmol P450 for o-HPA formation.

PMID- 11599931
TI  - Polymorphism of xenobiotic-metabolizing enzymes and excretion of styrene-specific
      mercapturic acids.
AB  - The role of polymorphic xenobiotic-metabolizing enzymes in the interindividual
      variability of phenylhydroxyethyl mercapturic acids (PHEMAs) was investigated in
      56 styrene-exposed workers. Ambient monitoring was carried out using passive
      personal samplers (geometric mean, 157 mg/m3 8-h time-weighted average; geometric
      standard deviation, 2.90). Biomonitoring was based on mandelic acid and
      phenylglyoxylic acid in urine spot samples collected at the end of the work shift
      ("end-of-shift") and prior to the subsequent shift ("next morning"). Four PHEMA
      diastereoisomers, namely (R,R)-M1, (S,R)-M1, (S,R)-M2, and (R,R)-M2, were
      determined by HPLC/tandem mass spectrometry. The genotypes of glutathione S
      transferases M1-1 (GSTM1), T1-1 (GSTT1) and P1-1 (GSTP1), and microsomal epoxide
      hydrolase (EPHX) were characterized by PCR-based methods. Workers bearing the
      GSTM1pos genotype showed PHEMA concentrations five and six times higher (in end
      of-shift and next-morning samples, respectively) as compared to GSTM1null people.
      In GSTM1pos subjects, (R,R)-M1 was the main mercapturate affected by the GSTM1
      status, accounting for 54 and 68% of total PHEMAs in end-of-shift and next
      morning samples, respectively. Compared to GSTM1null, GSTM1pos subjects excreted
      more -M1 than -M2 and more (R,R)-M1 and (S,R)-M2 than (S,R)-M1 and (R,R)-M2
      diastereoisomers. Thus, GSTM1-1 is the main isoenzyme catalyzing GSH-conjugation
      of styrene-7,8-oxide in humans and it seems to act in a regio- and
      stereoselective way. PHEMAs cannot be recommended as biomarkers of exposure to
      styrene, unless the GSTM1 genotype is considered in data interpretation. Their
      role as biomarkers of susceptibility deserves further studies.

PMID- 11599932
TI  - NMR and pattern recognition studies on the time-related metabolic effects of
      alpha-naphthylisothiocyanate on liver, urine, and plasma in the rat: an
      integrative metabonomic approach.
AB  - We present here a novel integrative metabonomic approach to probe toxic effects
      of drugs in experimental animals using alpha-naphthylisothiocyanate (ANIT) as a
      model hepatotoxicant. Male Han-Wistar rats were dosed with ANIT (150 mg/kg, n =
      25), and plasma and liver samples were collected for NMR and magic-angle spinning
      (MAS) NMR spectroscopy at 3, 7, 24, 31, and 168 h postdosing. Urine was collected
      continuously for 3 days prior to dosing and up to 168 h postdose. Histopathology
      and plasma clinical chemistry was also performed at all time points. Liver
      samples were analyzed either intact by 600 MHz 1H MAS NMR techniques or using
      high resolution (liquid state) 1H NMR of water-acetonitrile extracts. These data
      were related to sequential 1H NMR measurements in urine and plasma using pattern
      recognition methods. 1D 1H NMR spectra were data-reduced and analyzed using
      principal components analysis (PCA) to show the time-dependent biochemical
      variations induced by ANIT toxicity. From the eigenvector loadings of the PCA,
      those regions of the 1H NMR spectra and hence the combinations of endogenous
      metabolites marking the main phase of the toxic episode were identified. The ANIT
      induced biochemical manifestations included a hepatic lipidosis associated with
      hyperlipidaemia; hyperglycaemia and glycosuria; increased urinary excretion of
      taurine and creatine; a shift in energy metabolism characterized by increased
      plasma ketone bodies with reduced urinary excretion of tricarboxylic acid cycle
      intermediates and raised hepatic bile acids leading to bile aciduria. The
      integration of metabolic data derived from several sources gives a holistic
      approach to the study of time-related toxic effects in the intact system and
      enables the characterization of key metabolic effects during the development and
      recovery from a toxic lesion.

PMID- 11599933
TI  - Characterization of a 5'-aldehyde terminus resulting from the oxidative attack at
      C5' of a 2-deoxyribose on DNA.
AB  - The 5'-aldehyde terminus is a DNA oxidative damage resulting from attack at C5'
      of 2-deoxyriboses by some potent natural or chemical DNA cleavers. To offer a
      fast and specific method for characterization of this type of damage, we used on
      line electrospray ionization mass spectrometry (ESI-MS) detection during liquid
      chromatography analyses. The intrinsic reactivity of 5'-aldehyde terminus with
      nucleophiles (formation of hydrate with water, of a Tris adduct with Tris buffer)
      or through beta-elimination reaction resulted in complex LC profiles and MS data.
      We showed that derivatization of the aldehyde function as an oxime ether gives a
      stable derivative easy to characterize during on-line ESI-MS analyses. Complete
      structural characterization of the Tris adduct and the oxime ether derivative
      were obtained from MS and detailed NMR studies performed on derivatized 5'
      aldehyde thymidine models.

PMID- 11599934
TI  - Acrylonitrile enhances H2O2-mediated DNA damage via nitrogen-centered radical
      formation.
AB  - Acrylonitrile (ACN) is widely used as a monomer in the polymer industry. Studies
      on carcinogenicity in rats exposed to ACN showed increased incidences of tumors
      including glial cell tumors of central nervous system and increased production of
      8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in glial cells. Using a high
      performance liquid chromatograph equipped with an electrochemical detector, we
      revealed that ACN enhanced the formation of 8-oxo-dG induced by H2O2 and Cu(II)
      whereas ACN itself did not cause DNA damage. The enhancing effect of ACN was much
      more efficient in the double-stranded DNA than that in the single-stranded DNA.
      Experiments with 32P-labeled DNA revealed that addition of ACN enhanced the site
      specific DNA damage at guanines, particularly at 5'-site of the GG and GGG
      sequences while H2O2/Cu(II) induced piperidine-labile sites at thymine, cytosine,
      and guanine residues. An electron spin resonance spectroscopy using alpha-(4
      pyridyl-1-oxide)-N-tert-butylnitrone showed that a nitrogen-centered radical was
      generated from ACN in the presence of H2O2 and Cu(II). It is considered that ACN
      enhances H2O2-mediated DNA damage via nitrogen-centered radical formation. We
      will discuss the mechanism of the enhancing effect on oxidative DNA damage in
      relation to expression of ACN carcinogenicity.

PMID- 11599935
TI  - Metabolic profiling of chronic cadmium exposure in the rat.
AB  - A confounding problem with studying the effects of environmental exposure to
      contaminants in wild populations is that analytical techniques are invasive,
      particularly where the physiological effects of the toxin are assessed. In this
      study, a metabonomic approach to investigate the biochemical effects of chronic
      oral exposure to environmentally realistic doses of CdCl2 (low, 8 mg/kg; high, 40
      mg/kg) is presented. 1H NMR spectra of urine from exposed animals were analyzed
      using pattern recognition methods to identify biomarkers for a 94 day exposure
      period. Creatinuria and both increased excretion and complexation of citrate was
      detected after 19 days of exposure in both exposure groups. This was accompanied
      by a decrease in plasma Ca2+/Mg2+ ratio in blood plasma after 94 days. Post
      mortem, magic angle spinning (MAS) 1H NMR spectroscopy was used alongside
      conventional analytical techniques to investigate intact tissue directly.
      According to atomic absorption spectroscopy, kidney tissue accumulated 26.8 +/-
      2.5 microg of Cd2+/g dry wt (low) and 75.9 +/- 4.3 microg of Cd2+/g dry wt
      (high). Using high-resolution MAS 1H NMR spectroscopy altered lipid content was
      detected in kidneys from animals exposed to Cd2+. However, unlike acute exposure,
      no testicular damage was evident. This systemic approach to metabolism
      demonstrated the different physiological effects of chronic subacute compared
      with an acute exposure to Cd2+.

PMID- 11599936
TI  - Reactions of alpha-acetoxy-N-nitrosopyrrolidine with deoxyguanosine and DNA.
AB  - We investigated the reactions of alpha-acetoxy-N-nitrosopyrrolidine (alpha
      acetoxyNPYR) with dGuo and DNA. Alpha-acetoxyNPYR is a stable precursor to the
      major proximate carcinogen of NPYR, alpha-hydroxyNPYR (3). Our goal was to
      develop appropriate conditions for the analysis of DNA adducts of NPYR formed in
      vivo. Products of the alpha-acetoxyNPYR-dGuo reactions were analyzed directly by
      HPLC or after treatment of the reaction mixtures with NaBH3CN. Products of the
      alpha-acetoxyNPYR-DNA reactions were released by enzymatic or neutral thermal
      hydrolysis of the DNA, then analyzed by HPLC. Alternatively, the DNA was treated
      with NaBH3CN prior to hydrolysis and HPLC analysis. The reactions of alpha
      acetoxyNPYR with dGuo and DNA were complex. We have identified 13 products of the
      dGuo reaction-6 of these were characterized in this reaction for the first time.
      They were four diastereomers of N2-(3-hydroxybutylidene)dGuo (20, 21), 7-(N
      nitrosopyrrolidin-2-yl)Gua (2), and 2-(2-hydroxypyrrolidin-1-yl)deoxyinosine
      (12). Adducts 20 and 21 were identified by comparison to standards produced in
      the reaction of 3-hydroxybutanal with dGuo. Adduct 2 was identified by its
      spectral properties while adduct 12 was characterized by comparison to an
      independently synthesized standard. With the exception of adduct 2, all products
      of the dGuo reactions were also observed in the DNA reactions. The major product
      in both the dGuo and DNA reactions was N2-(tetrahydrofuran-2-yl)dGuo (10),
      consistent with previous studies. Several other previously identified adducts
      were also observed in this study. HPLC analysis of reaction mixtures treated with
      NaBH3CN provided improved conditions for adduct identification, which should be
      useful for in vivo studies of DNA adduct formation by NPYR.

PMID- 11599937
TI  - Animal species difference in the uptake of dimethylarsinous acid (DMA(III)) by
      red blood cells.
AB  - The animal species difference in the metabolism of arsenic was studied from the
      viewpoint of the mechanism underlying its distribution in the form of
      dimethylated arsenic in red blood cells (RBCs). Dimethylarsinic (DMA(V)) and
      dimethylarsinous (DMA(III)) acids were incubated with rat, hamster, mouse, and
      human RBCs, and the uptake rates and chemical forms of arsenic were determined.
      Although DMA(V) was practically not or taken up slowly by RBCs of all the present
      animal species, DMA(III) was taken efficiently in the order of rat > hamster >
      human, RBCs of mice taking it up less efficiently and with a different pattern
      from the former three animals. Further, although DMA(III) taken up by rat RBCs
      was retained, that by hamster ones was effluxed in the form of DMA(V). The uptake
      of DMA(III) and efflux of DMA(V) took place much more slowly in human RBCs than
      rat and hamster ones. The uptake of DMA(III) by RBCs was inhibited on the
      oxidation of glutathione with diamide. Incubation of DMA(III), but not of DMA(V),
      with a hemolysate produced a high molecular weight complex, which increases in
      the presence of glutathione, suggesting that DMA(III) taken up by RBCs is
      retained through the formation of a complex with protein(s) specific to animal
      species, and effluxed from RBCs after being oxidized to DMA(V). These results
      indicate that DMA is taken up by RBCs in the form of DMA(III), and that the
      uptake and efflux rates are dependent on the animal species, the effluxed arsenic
      being DMA(V). The present results suggest that the uptake of DMA by RBCs is an
      additional contributing factor to the animal species difference in the metabolism
      of arsenic in addition to the reduction and methylation capacity in the liver.

PMID- 11599938
TI  - Absolute rate constants for the reaction of hypochlorous acid with protein side
      chains and peptide bonds.
AB  - Hypochlorous acid (HOCl) is a potent oxidant, which is produced in vivo by
      activated phagocytes. This compound is an important antibacterial agent, but
      excessive or misplaced production has been implicated in a number of human
      diseases, including atherosclerosis, arthritis, and some cancers. Proteins are
      major targets for this oxidant, and such reaction results in side-chain
      modification, backbone fragmentation, and cross-linking. Despite a wealth of
      qualitative data for such reactions, little absolute kinetic data is available to
      rationalize the in vitro and in vivo data. In this study, absolute second-order
      rate constants for the reactions of HOCl with protein side chains, model
      compounds, and backbone amide (peptide) bonds have been determined at
      physiological pH values. The reactivity of HOCl with potential reactive sites in
      proteins is summarized by the series: Met (3.8 x 10(7) M(-1) x s(-1)) > Cys (3.0
      x 10(7) M(-1) x s(-1)) >> cystine (1.6 x 10(5) M(-1) x s(-1)) approximately His
      (1.0 x 10(5) M(-1) x s(-1)) approximately alpha-amino (1.0 x 10(5) M(-1) x s(-1))
      > Trp (1.1 x 10(4) M(-1) x s(-1)) > Lys (5.0 x 10(3) M(-1) x s(-1)) >> Tyr (44 M(
      1) x s(-1)) approximately Arg (26 M(-1) x s(-1)) > backbone amides (10-10(-3) M(
      1) x s(-1)) > Gln(0.03 M(-1) x s(-1)) approximately Asn (0.03 M(-1) x s(-1)). The
      rate constants for reaction of HOCl with backbone amides (peptide bonds) vary by
      4 orders of magnitude with uncharged peptide bonds reacting more readily with
      HOCl than those in a charged environment. These kinetic parameters have been used
      in computer modeling of the reactions of HOCl with human serum albumin,
      apolipoprotein-A1 and free amino acids in plasma at different molar excesses.
      These models are useful tools for predicting, and reconciling, experimental data
      obtained in HOCl-induced oxidations and allow estimations to be made as to the
      flux of HOCl to which proteins are exposed in vivo.

PMID- 11599939
TI  - Cesium(I)-mediated 3-D superstructures by one-pot self-organization of hydrogen
      bonded nickel complexes.

PMID- 11599940
TI  - The ordered [WO(2)F(4)](2-) anion.

PMID- 11599941
TI  - A platinum(IV) complex oxidizes guanine to 8-oxo-guanine in DNA and RNA.

PMID- 11599942
TI  - Modeling the reactivity of superoxide reducing metalloenzymes with a nitrogen and
      sulfur coordinated iron complex.

PMID- 11599943
TI  - 2,6-Dipyrazinylpyridines and their ruthenium(II) complexes: a new polynucleating
      ligand family.

PMID- 11599944
TI  - Linking two alkyne-bridged dicobalt complexes via a urea-based ligand: synthesis
      and spectroscopic and structural characterization of [[Co(2)(CO)(6)(mu-HC
      identical with C-)]-CH(2)NH](2)C=O.

PMID- 11599945
TI  - Functionalization of [MoW(5)O(19)](2-) with aromatic amines: synthesis of the
      first arylimido derivatives of mixed-metal polyoxometalates.

PMID- 11599946
TI  - Reaction of the uranyl(VI) ion (UO(2)(2+)) with a triamidoamine ligand:
      preparation and structural characterization of a mixed-valent uranium(V/VI) oxo
      imido dimer.
AB  - The synthesis and structural characterization of a mixed-valent uranium(V/VI) oxo
      imido complex are reported. Reaction of the uranyl chloride complex [K(18-crown
      6)](2)[UO(2)Cl(4)] (1) with the triamidoamine ligand
      Li(3)[N(CH(2)CH(2)NSiBu(t)Me(2))(3)] yields oxo-imido [K(18-crown
      6)(Et(2)O)][UO(mu(2)-NuCH(2)CH(2)N(CH(2)CH(2)NSiBu(t)Me(2))(2))](2) (2) as the
      major isolated uranium product in moderate yield. The reaction that forms 2
      involves activation of both the triamidoamine ligand and the uranyl dioxo unit of
      1. An X-ray crystal structure determination of 2 reveals a dimeric complex in
      which the coordination geometry at each uranium center is that of a capped
      trigonal bipyramid. The multidentate triamidoamine ligand coordinates to uranium
      through the capping amine and two of the three pendant amido ligands, while the
      third pendant amido donor has been activated to generate a bridging imido ligand
      by loss of the silyl substituent. One of the uranyl oxo groups is retained as a
      terminal ligand to complete the coordination sphere for each uranium center. The
      oxo and imido nitrogen may be regarded as the axial ligands of the trigonal
      bipyramid, while the two amido ligands and the other imido donor occupy
      equatorial coordination sites. The central amine of the tripodal set serves as
      the capping ligand. Distortion of the axial O-U-N angle from 180 degrees emanates
      from the proximity of the capping amine and the bridging interaction to the other
      uranium center. The structure and bonding in 2 are assessed in the context of
      metal-ligand multiple bonding in high-valent actinide complexes. The possibility
      of valence averaging [5.5/5.5 vs 5.0/6.0] via delocalization or rapid
      intramolecular electron-transfer dynamics of the unpaired electron is also
      discussed in the context of crystallographic, spectroscopic (NMR, IR, Raman, and
      EPR), and electrochemical data. Crystal data for 2: triclinic space group P1
      macro, a = 12.1144(6) A, b = 12.6084(6) A, c = 14.5072(7) A, alpha = 101.374(1)
      degrees, beta = 103.757(1) degrees, gamma = 109.340(1) degrees, z = 1, R1 =
      0.0523, wR2 = 0.1359.

PMID- 11599947
TI  - Influence of Jahn-Teller coupling on the magnetic properties of transition metal
      complexes with orbital triplet ground terms: magnetization and electronic Raman
      studies of the titanium(III) hexa-aqua cation.
AB  - Magnetization and electronic Raman data are presented for salts of the type
      Cs[Ga:Ti](SO(4))(2) x 12H(2)O, which enable a very precise definition of the
      electronic structure of the [Ti(OH(2))(6)](3+) cation. The magnetization data
      exhibit a spectacular deviation from Brillouin behavior, with the magnetic moment
      highly dependent on the strength of the applied field at a given ratio of B/T.
      This arises from unprecedented higher-order contributions to the magnetization,
      and these measurements afford the determination of the ground-state Zeeman
      coefficients to third-order. The anomalous magnetic behavior is a manifestation
      of Jahn-Teller coupling, giving rise to low-lying vibronic states, which mix into
      the ground state through the magnetic field. Electronic Raman measurements of the
      1%-titanium(III)-doped sample identify the first vibronic excitation at
      approximately 18 cm(-1), which betokens a substantial quenching of spin-orbit
      coupling by the vibronic interaction. The ground-state Zeeman coefficients are
      strongly dependent on the concentration of titanium(III) in the crystals, and
      this can be modeled as a function of one parameter, representing the degree of
      strain induced by the cooperative Jahn-Teller effect. This study clearly
      demonstrates the importance that the Jahn-Teller effect can have in governing the
      magnetic properties of transition metal complexes with orbital triplet ground
      terms.

PMID- 11599948
TI  - Porphyrinic dyads and triads assembled around iridium(III) bis-terpyridine:
      photoinduced electron transfer processes.
AB  - Multicomponent arrays based on a central iridium(III) bis-terpyridine complex
      (Ir) used as assembling metal and free-base, zinc(II) or gold(III) tetraaryl
      porphyrins (PH(2), PZn, PAu) have been designed to generate intramolecular
      photoinduced charge separation. The rigid dyads PH(2)-Ir, PZn-Ir, PAu-Ir, and the
      rigid and linear triads PH(2)-Ir-PAu, PZn-Ir-PAu, as well as the individual
      components Ir, PH(2), PZn, PAu have been synthesized and characterized by various
      techniques including electrochemistry. Their photophysical properties either in
      acetonitrile or in dichloromethane and toluene have been determined by steady
      state and time-resolved methods. In acetonitrile, excitation of the triad PH(2)
      Ir-PAu leads to a charge separation with an efficiency of 0.5 and a resulting
      charge-separated (CS) state with a lifetime of 3.5 ns. A low-lying triplet
      localized on PH(2) and the presence of the heavy Ir(III) ion offer the CS state
      an alternative deactivation path through the triplet state. The behavior of the
      triad PZn-Ir-PAu in dichloromethane is rather different from that of PH(2)-Ir-PAu
      in acetonitrile since the primary electron transfer to yield PZn(+)()-Ir(-)-PAu
      is not followed by a secondary electron transfer. In this solvent, both
      unfavorable thermodynamic and electronic parameters contribute to the
      inefficiency of the second electron-transfer reaction. In contrast, in toluene
      solutions, the triad PZn-Ir-PAu attains a CS state with a unitary yield and a
      lifetime of 450 ns. These differences can be understood in terms of ground-state
      charge-transfer interactions as well as different stabilization of the
      intermediate and final CS states by solvent.

PMID- 11599949
TI  - Experimental and theoretical studies on ferromagnetically coupled metal complexes
      with imino nitroxides.
AB  - Copper(II), zinc(II), and nickel(II) complexes with tridentate imino nitroxyl
      diradicals, [CuCl(bisimpy)(MeOH)](PF(6)) (1), [ZnCl(2)(bisimpy)] (2), and
      [NiCl(bisimpy)(H(2)O)(2)]Cl x 2H(2)O (3) (bisimpy = 2,6-bis(1'-oxyl-4',4',5',5'
      tetramethyl-4',5'-dihydro-1'H-imidazol-2'-yl)pyridine), were prepared, and their
      magnetic properties were studied. In 1, the Cu(II) ion has a square pyramidal
      coordination geometry, of which the equatorial coordination sites are occupied by
      three nitrogen atoms from the bisimpy and a chloride ion. The coordination
      geometry of the Zn(II) ion in 2 can be described as a trigonal bipyramid, with
      two chloride ions and a bisimpy. In 3, the Ni(II) ion has a distorted octahedral
      coordination geometry, of which four coordination sites are coordinated by the
      bisimpy and chloride ion, and two water molecules occupy the remaining cis
      positions. Magnetic susceptibility and EPR measurements revealed that in 1 and 3
      the Cu(II) and Ni(II) ions with imino nitroxyl diradicals were ferromagnetically
      coupled, with the coupling constants J (H = -2J(ij) summation operator S(i)S(j))
      of +165(1) and 109(2) cm(-1), respectively, and the intraligand ferromagnetic
      interactions in 1-3 were very weak. DFT molecular orbital calculations were
      performed on the diradical ligand, 1, and 2 to study the spin density
      distribution before and after coordination to the metal ions.

PMID- 11599950
TI  - Syntheses, crystal structures, and magnetic properties of one-dimensional oxalato
      bridged Co(II), Ni(II), and Cu(II) complexes with n-aminopyridine (n = 2-4) as
      terminal ligand.
AB  - The reaction of M(ox) x 2H(2)O (M = Co(II), Ni(II)) or K(2)(Cu(ox)(2)) x 2H(2)O
      (ox = oxalate dianion) with n-ampy (n = 2, 3, 4; n-ampy = n-aminopyridine) and
      potassium oxalate monohydrate yields one-dimensional oxalato-bridged metal(II)
      complexes which have been characterized by FT-IR spectroscopy, variable
      temperature magnetic measurements, and X-ray diffraction methods. The complexes
      M(mu-ox)(2-ampy)(2) (M = Co (1), Ni (2), Cu (3)) are isomorphous and crystallize
      in the monoclinic space group C2/c (No. 15), Z = 4, with unit cell parameters for
      1 of a = 13.885(2) A, b = 11.010(2) A, c = 8.755(1) A, and beta = 94.21(2)
      degrees. The compounds M(mu-ox)(3-ampy)(2).1.5H(2)O (M = Co (4), Ni (5), Cu (6))
      are also isomorphous and crystallize in the orthorhombic space group Pcnn (No.
      52), Z = 8, with unit cell parameters for 6 of a = 12.387(1), b = 12.935(3), and
      c = 18.632(2) A. Compound Co(mu-ox)(4-ampy)(2) (7) crystallizes in the space
      group C2/c (No. 15), Z = 4, with unit cell parameters of a = 16.478(3) A, b =
      5.484(1) A, c = 16.592(2) A, and beta = 117.76(1) degrees. Complexes M(mu-ox)(4
      ampy)(2) (M = Ni (8), Cu (9)) crystallize in the orthorhombic space group Fddd
      (No. 70), Z = 8, with unit cell parameters for 8 of a = 5.342(1), b = 17.078(3),
      and c = 29.469(4) A. All compounds are comprised of one-dimensional chains in
      which M(n-ampy)(2)(2+) units are sequentially bridged by bis-bidentate oxalato
      ligands with M.M intrachain distances in the range of 5.34-5.66 A. In all cases,
      the metal atoms are six-coordinated to four oxygen atoms, belonging to two
      bridging oxalato ligands, and the endo-cyclic nitrogen atoms, from two n-ampy
      ligands, building distorted octahedral surroundings. The aromatic bases are bound
      to the metal atom in cis (1-6) or trans (7-9) positions. Magnetic susceptibility
      measurements in the temperature range of 2-300 K show the occurrence of
      antiferromagnetic intrachain interactions except for the compound 3 in which a
      weak ferromagnetic coupling is observed. Compound 7 shows spontaneous
      magnetization below 8 K, which corresponds to the presence of spin canted
      antiferromagnetism.

PMID- 11599951
TI  - A molecular box derived from cobaloxime units held together by 4-pyridinylboronic
      acid residues.
AB  - The reaction of CH(3)Co(DH)(2)H(2)O with 4-pyridinyl boronic acid in methanol or
      water affords the dinuclear complexes [MeCo(DH)(DB(OR)(4-Py))](2), with R = Me
      (2) or H (3), respectively, through reaction of boron with the oxime oxygens of
      the alkylcobaloxime and coordination of the pyridinyl N to cobalt. The reaction
      is strongly pH dependent, and the formation of the complexes requires a neutral
      medium. The complexes have been fully characterized by (1)H and (13)C NMR
      spectroscopy, ESI-MS spectrometry, and elemental analysis. The X-ray structure
      shows that in 2, the pyridinyl groups are facing each other and nearly
      perpendicular both to the plane of the Co B Co1 B1 atoms and to the mean
      equatorial plane, so that the complex may be considered a molecular box. A
      dimeric arrangement has already been found in the related [MeCo(DH)(DB(OMe)(3
      Py))](2) (1) complex, which forms a distorted molecular rectangle [Dreos, R.;
      Nardin, G.; Randaccio, L.; Tauzher, G.; Vuano, S. Inorg. Chem. 1997, 36, 2463].
      The dimerization is possible in both cases, as the conformational freedom of the
      B bridge compensates for the different position (3- or 4-) of the pyridinyl N
      donor.

PMID- 11599952
TI  - A new organocobalt complex containing a CO-N-C three membered ring.
AB  - Treatment of R = -CH(2)X (X = halogen) derivatives of the type [RCo(III)(LNH
      py)(HLNH-py)](+), where HLNH-py = 2-(2-pyridyl-ethyl)amino-3-butanone oxime and
      LNH-py its conjugated base with diluted NaOH, afforded a new complex containing a
      three-membered ring by a pathway involving the intramolecular nucleophilic
      addition of an equatorial nitrogen donor to the axial carbon. The X-ray analysis
      reveals a highly distorted structure. The C-Co-N angle is acute (42.8 degrees )
      with the distortion of the coordination sphere concentrated in the Co-C axial and
      Co-N bonds, which move away from the pseudo-octahedral positions in the CH(2)X
      parent complex to form the C-N bond of the metallocycle. Kinetic studies of the
      formation of this novel complex starting from [(XCH(2)Co(III)(LNH-py)(HLNH
      py)](+) (X = Cl,Br,I) showed that the metallocycle formation rates increase in
      the order Cl < Br < I. Kinetic data are consistent with a mechanism involving an
      intermediate species resulting from the deprotonation of an amine equatorial
      nitrogen in a rapid preequilibrium, followed by the slow step of the ring
      closure.

PMID- 11599953
TI  - Facile allylic C-H bond activation on the bridging disulfide ligand in the
      Ru(III) dinuclear complex having a conjugated RuSSRu core.
AB  - Treatment of [[Ru(P(OCH(3))(3))(2)(CH(3)CN)(3)](2)(mu-S(2))](CF(3)SO(3))(4) (1),
      which is prepared by the reaction of [[RuCl(P(OCH(3))(3))(2)](2)(mu-S(2))(mu
      Cl)(2)] (2) with 4 equiv of AgCF(3)SO(3), with terminal alkenes such as 1
      pentene, allyl ethyl ether, allyl phenyl ether, 1,4-hexadiene, and 3-methyl-1
      butene, resulted in the formation of complexes carrying a C(3)S(2) five-membered
      ring, [[Ru(P(OCH(3))(3))(2)(CH(3)CN)(3)](2)[mu
      SCH(2)CH(2)CR(1)R(2)S]](CF(3)SO(3))(4) (3, R(1) = CH(2)CH(3), R(2) = H, 40%; 4,
      R(1) = OCH(2)CH(3), R(2) = H, 60%; 5, R(1) = OC(6)H(5), R(2) = H, 73%; 6, R(1) =
      CH=CHCH(3), R(2) = H, 48%; 7, R(1) = R(2) = CH(3), 40%). Reaction of 1 with
      methylenecycloalkanes was found to give several different types of products,
      depending on the ring size of the substrates. A trace of
      [[Ru(P(OCH(3))(3))(2)(CH(3)CN)(3)](2)[mu
      SCH(CH(2)CH(2))CH(CH(3))S]](CF(3)SO(3))(4) (9) having a C(2)S(2) four-membered
      ring to bridge the two Ru atoms was obtained by the reaction of 1 with
      methylenecyclobutane, whereas the reaction with methylenecyclohexane gave
      [[Ru(P(OCH(3))(3))(2)(CH(3)CN)(3)](2)[mu
      S(CH(2)(C=CHCH(2)CH(2)CH(2)CH(2))S)](CF(3)SO(3))(3) (10) in 69% yield via C-S
      bond formation and elimination of a proton. Throughout these reactions with
      alkenes giving a variety of products, the activation of the allylic C-H bond is
      always the essential and initial key step.

PMID- 11599954
TI  - Synthesis, structure, electrochemistry, and spectroelectrochemistry of
      hypervalent phosphorus(V) octaethylporphyrins and theoretical analysis of the
      nature of the PO bond in P(OEP)(CH(2)CH(3))(O).
AB  - A variety of phosphorus(V) octaethylporphyrin derivatives of the type
      [P(OEP)(X)(Y)](+)Z(-) (OEP: octaethylporphyrin) (X = CH(3), CH(2)CH(3), C(6)H(5),
      F; Y = CH(3), CH(2)CH(3), OH, OCH(3), OCH(2)CH(3), On-Pr, Oi-Pr, Osec-Bu, NHBu,
      NEt(2), Cl, F, O(-); Z = ClO(4), PF(6)) were prepared. X-ray crystallographic
      analysis of eleven compounds reveals that the degree of ruffling of the porphyrin
      core becomes greater and the average P-N bond distance becomes shorter as the
      axial ligands become more electronegative. Therefore, the electronic effect of
      the axial substituents plays a major role in determining the degree of ruffling
      although the steric effect of the substituents plays some role. A comparison of
      the (1)H NMR chemical shifts for the series of [P(OEP)(CH(2)CH(3))(Y)](+)Z(-)
      complexes with those of the corresponding arsenic porphyrins, which possess a
      planar core, indicates a much smaller ring current effect of the porphyrin core
      in the severely ruffled phosphorus porphyrins. The electrochemistry,
      spectroelectrochemistry and ESR spectroscopy of the singly reduced compounds are
      also discussed. The OH protons of [P(OEP)(X)(OH)](+) are acidic enough to
      generate P(OEP)(X)(O) by treatment with aq dilute NaOH. X-ray analysis of
      P(OEP)(CH(2)CH(3))(O) reveals that the PO bond length is very short (1.475(7) A)
      and is comparable to that in triphenylphosphine oxide (1.483 A). The features of
      the quite unique hexacoordinate hypervalent compounds are investigated by density
      functional calculation of a model (Por)P(CH(2)CH(3))(O) and (Por)P(F)(O) (Por:
      unsubstituted porphyrin).

PMID- 11599955
TI  - Achiral tetrahydrosalen ligands for the synthesis of C(2)-symmetric titanium
      complexes: a structure and diastereoselectivity study.
AB  - Achiral tetrahydrosalen ligands have been employed in the synthesis of chiral
      C(2)-symmetric titanium complexes. When combined with tetrahydrosalen ligands 2a
      and 2b, titanium tetraisopropoxide liberated 2 equiv of isopropyl alcohol and
      generated the (tetrahydrosalen)Ti(O-i-Pr)(2) complexes 3a and 3b. These complexes
      were shown to be C(2)-symmetric by (1)H and (13)C[(1)H] NMR spectrometry and X
      ray crystallography. X-ray structures of 3a and 3b indicate that the bonding of
      the tetrahydrosalen ligand to titanium is different than the bonding of salen
      ligands to titanium. Whereas salen ligands usually bind to titanium in a planar
      arrangement, the tetrahydrosalen is bonded with the phenoxide oxygens mutually
      trans. When bound in this fashion, the nitrogens of the tetrahydrosalen ligand
      and the titanium become stereogenic centers. The use of titanium complexes of
      high enantiopurity in the generation of tetrahydrosalen titanium adducts resulted
      in a maximum diastereoselectivity of 2:1. The diastereoselectivity obtained using
      chiral titanium alkoxide complexes was greater than the diastereoselectivity
      observed when a tetrahydrosalen ligand derived from (S,S)-trans
      diaminocyclohexane was employed.

PMID- 11599956
TI  - Dynamic study of homoleptic bimetallic platinum(II) complexes bridged by
      fluorinated benzenethiolates.
AB  - A variable-temperature (19)F NMR study of the homoleptic bimetallic anionic
      complexes X(2)[Pt(2)(mu-SC(6)F(5))(2)(SC(6)F(5))(4)] (X = K(+), 1a; Bu(4)N(+),
      1b), X(2)[Pt(2)(mu-p-SC(6)HF(4))(2)(p-SC(6)HF(4))(4)] (X = K(+), 2a; Bu(4)N(+),
      2b), and X(2)[Pt(2)(mu-p-SC(6)F(4)(CF(3)))(2)(p-SC(6)F(4)(CF(3)))(4)] (X = K(+),
      3a; Bu(4)N(+), 3b) demonstrates the occurrence of dynamic processes that give
      rise to several stereoisomeric species in solution. Experimental evidence
      suggests that both inversion of configuration at the sulfur bridging atoms and
      hindered rotation about the carbon-sulfur bond are involved in generating the
      observed isomers. The solid-state X-ray diffraction structures of compounds 1b,
      2b, and 3b show that all three complexes contain planar [Pt(2)(mu-S)(2)] rings
      with an anti configuration.

PMID- 11599957
TI  - Synthesis, structure, and magnetism of bimetallic manganese or nickel complexes
      of a bridging verdazyl radical.
AB  - Two binuclear metal-radical complexes, formed by the reaction of M(hfac)(2) x
      2H(2)O (M = Mn or Ni; hfac = hexafluoroacetylacetonate) with the 1,5-dimethyl-3
      (4,6-dimethylpyrimidin-2-yl)-6-oxoverdazyl radical (3), were synthesized. The
      binuclear Mn complex 5 (i.e., 3[Mn(hfac)(2)](2)) crystallizes in the monoclinic
      space group C2/c: C(30)H(17)N(6)O(9)F(24)Mn(2), a = 29.947(3), b = 17.143(3), c =
      16.276(3) A, beta = 123.748(3)*, Z = 4. The compound consists of two pseudo
      octahedral Mn(II) ions, both bearing two hfac ancillary ligands, bridged by the
      bis(bidentate) radical 3. The temperature dependence of the magnetic
      susceptibility of 5 reveals moderate antiferromagnetic exchange between each of
      the Mn(II) ions and the verdazyl radical (J = -48 cm(-1)). The S = 9/2 ground
      spin state of the complex was corroborated by low-temperature magnetization
      versus field measurements. In contrast, the magnetic susceptibility versus
      temperature behavior of 6 (whose molecular structure is presumed to be analogous
      to that of 5) indicates that the two Ni(II) ions are strongly ferromagnetically
      coupled to the verdazyl radical (J = +220 cm(-1)). The magnetization versus field
      behavior of 5 is consistent with an S = 5/2 ground-state species.

PMID- 11599958
TI  - Ring-opening and meso substitution from the reaction of cyanide ion with zinc
      verdohemes.
AB  - The reactivity of zinc verdoheme, [Zn(II)(OEOP)](O(2)CCH(3)) where OEOP is the
      monoanion of octaethyl-5-oxaporphyrin, with cyanide ion has been shown to be a
      complex process that involves not only the expected ring-opening of the
      macrocycle, as occurs with other nucleophiles (methoxide, methanethiolate,
      dimethylamide), but also substitution at one or two of the meso positions. The
      ring-opened products have been subjected to crystallographic study. The
      structures of mu-H(2)O-[Zn(II)(OEB-10,19-(CN)(2))](2) and mu-H(2)O-[(Zn(II)(OEB
      10,15,19-(CN)(3))](2) both consist of two helical tetrapyrrole subunits that are
      coordinated to a zinc ion through four Zn-N bonds. The two zinc ions are
      coordinated to a bridging water molecule that is also hydrogen bonded to a lactam
      oxygen atom at one end of each tetrapyrrole subunit. Thus the chiral sense of one
      helical Zn(II)(OEB-10,19-(CN)(2)) portion is transmitted to the other Zn(II)(OEB
      10,19-(CN)(2)) unit and the resulting binuclear unit is chiral. In contrast
      Co(II)(OEB-15,19-(CN)(2)), which was obtained by the insertion of Co(II) into the
      free ligand, is monomeric with a four-coordinate cobalt ion. A series of DFT
      geometry optimization calculations were performed on zinc complexes of 5
      oxaporphyrins (verdoheme), verdins (bilindione), 4-cyano-5-oxaporphyrins, and 19
      cyanoverdins in an effort to gain insights to the features of these complexes and
      the reactions that lead to meso-cyano-substituted cyanoverdins.

PMID- 11599960
TI  - Bonding to titanium.
AB  - The recent synthesis of a crystalline compound containing Ti bonded to
      cyclopentadienyl and a substituted dienyl fragment prompted the question of
      whether Ti-C contacts that were found to be shorter than other such bonded
      contacts in the same molecule should be considered as short nonbonded contacts or
      "nonclassical metal-to-saturated-carbon atom interactions", fitting the
      description of agostic interactions. This question has a unique answer within the
      framework of the quantum theory of atoms in molecules (QTAIM). QTAIM uses the
      measurable electron density to assign a molecular structure and the physics of an
      open system to determine the nature of the bonded interactions. All of the
      classical bonding descriptors, when recast in terms of the topologies of the
      electron density and the pair density, are faithfully recovered when QTAIM is
      applied to the hydrocarbon framework of the Ti complex, thereby justifying its
      application to the analysis of the Ti-C interactions. No bond paths are found to
      link the Ti to the carbons exhibiting the "short contacts", and the topology of
      the density gives no indication of an incipient change in structure that would
      result in their formation.

PMID- 11599959
TI  - 2.4 A crystal structure of an oxaliplatin 1,2-d(GpG) intrastrand cross-link in a
      DNA dodecamer duplex.
AB  - (1R,2R-Diaminocyclohexane)oxalatoplatinum(II) (oxaliplatin) is a third-generation
      platinum anticancer compound that produces the same type of inter- and
      intrastrand DNA cross-links as cisplatin. In combination with 5-fluorouracil,
      oxaliplatin has been recently approved in Europe, Asia, and Latin America for the
      treatment of metastatic colorectal cancer. We present here the crystal structure
      of an oxaliplatin adduct of a DNA dodecanucleotide duplex having the same
      sequence as that previously reported for cisplatin (Takahara, P. M.; Rosenzweig,
      A. C.; Frederick, C. A.; Lippard, S. J. Nature 1995, 377, 649-652). Pt-MAD data
      were used to solve this first X-ray structure of a platinated DNA duplex derived
      from an active platinum anticancer drug other than cisplatin. The overall
      geometry and crystal packing of the complex, refined to 2.4 A resolution, are
      similar to those of the cisplatin structure, despite the fact that the two
      molecules crystallize in different space groups. The platinum atom of the [Pt(R,R
      DACH)](2+) moiety forms a 1,2-intrastrand cross-link between two adjacent
      guanosine residues in the sequence 5'-d(CCTCTGGTCTCC), bending the double helix
      by approximately 30 degrees toward the major groove. Both end-to-end and end-to
      groove packing interactions occur in the crystal lattice. The latter is
      positioned in the minor groove opposite the platinum cross-link. A novel feature
      of the present structure is the presence of a hydrogen bond between the
      pseudoequatorial NH hydrogen atom of the (R,R)-DACH ligand and the O6 atom of the
      3'-G of the platinated d(GpG) lesion. This finding provides structural evidence
      for the importance of chirality in mediating the interaction between oxaliplatin
      and duplex DNA, calibrating previously published models used to explain the
      reactivity of enantiomerically pure vicinal diamine platinum complexes with DNA
      in solution. It also provides a new kind of chiral recognition between an
      enantiomerically pure metal complex and the DNA double helix.

PMID- 11599961
TI  - Proposed fluorination mechanism of CB(5)H(6)(-) and CB(9)H(10)(-) with HF.
      Evidence of kinetic control in the formation of 2-CB(5)H(5)F(-) and 6-CB(9)H(9)F(
      ).
AB  - Two pathways have been considered in the fluorination of CB(5)H(6)(-) and
      CB(9)H(10)(-) by HF. In the ionic HF fluorination pathway, the monocarborane
      anion cage is first protonated in a BBB face followed by H(2) elimination and
      fluoride anion addition. In the covalent HF fluorination pathway, HF is first
      coordinated through hydrogen to the BBB face. Next, the fluorine can add to
      either an axial or equatorial boron atom which opens the cage to a nido structure
      with an endo fluoride substituent. Endo to exo rearrangement occurs with a small
      activation barrier followed by H(2) elimination. In both pathways, fluorination
      at the equatorial boron position is predicted to have smaller activation barriers
      even though substitution at the axial position leads to the more stable products.